PMID- 17171589
TI  - Prophylaxis and treatment of venous thromboembolism in individuals with inherited
      thrombophilia.
AB  - Venous thromboembolism (VTE) susceptibility genes are widely diffuse in the
      general population, but clinical penetrance of genotypes is incomplete and has
      variable expressivity. Therefore, the indiscriminate search for carriers is of
      doubtful utility and potentially detrimental for screened individuals. A targeted
      screening in kindreds in which VTE already occurred can be more fruitful in
      identifying individuals sharing with the proband one or more known susceptibility
      genes (possibly cosegregating with other ones still unknown). Clinical penetrance
      is variable, and is higher in the relatively rare deficiencies of antithrombin
      (AT), protein C (PC), or protein S (PS), and lower in the presence of the common
      polymorphisms factor V Leiden and prothrombin G20210A. Women with inherited
      thrombophilia should be warned about the thrombotic risk associated with the use
      of oral contraceptives or hormonal replacement treatment. Moreover, prophylaxis
      during puerperium and surgery or after trauma is warranted. The absolute risk
      associated with such situations is low but not negligible in the presence of
      deficiencies of AT, PC, or PS, homozygous conditions, and carriership of multiple
      defects. In such cases primary prophylaxis should be applied also during
      pregnancy and in general should be more stringent; moreover, in these patients
      the option for indefinite duration of secondary anticoagulant prophylaxis after
      VTE should be considered because of the relevant risk of recurrent VTE. In all
      cases, a careful balance of benefits and risks associated with prophylactic
      measures should be achieved, and patient preferences should be considered.

PMID- 17171590
TI  - Management of oral anticoagulant treatment in patients with venous
      thromboembolism.
AB  - Oral anticoagulants (OAs) are the drugs of choice for the prevention of
      recurrence and death in patients with venous thromboembolism (VTE). Oral
      anticoagulant treatment (OAT) aims to retard blood coagulation to obtain maximum
      protection against thromboembolic events with the lowest risk of bleeding. The
      intensity of OAT is ascertained by measuring the prothrombin time (PT), which is
      expressed as the international normalized ratio (INR). The efficacy and safety of
      these drugs depends on the ability to maintain the level of anticoagulation as
      close as possible to the therapeutic target (INR = 2.5) or inside the therapeutic
      range (INR = 2.0 to 3.0). Given that dosage of oral anticoagulants varies from
      patient to patient and within the single patient, clinical and laboratory
      (biological effect of the drug) check-ups must be performed periodically. The
      management of patients with VTE, as well as that of other patients receiving OAT,
      includes medical controls and expertise that are better available in specialized
      centers (anticoagulation clinics).

PMID- 17171591
TI  - New strategies for the treatment of acute venous thromboembolism.
AB  - In recent years, new opportunities have emerged that have the potential to change
      rapidly the therapeutic scenario of patients with acute venous thromboembolism
      (VTE). Selected patients with deep vein thrombosis (DVT) can be treated
      effectively and safely at home with fixed doses of low molecular weight heparins.
      The prompt administration of compression elastic stockings in addition to
      anticoagulant drugs in patients with acute DVT has the potential to halve the
      rate of late postthrombotic sequelae. The long-term use of low molecular weight
      heparins is likely to be more effective than oral anticoagulants for the
      secondary prevention of VTE in patients with advanced malignancy. Patients with
      pulmonary embolism and right ventricular dysfunction might benefit from the early
      administration of thrombolytic drugs in combination with heparin to a greater
      extent than from heparin alone. Despite an impressive amount of clinical
      information on the proper duration of oral anticoagulants in patients with
      unprovoked VTE, the optimal long-term treatment of these patients remains
      undefined. Finally, new categories of drugs are emerging that have the potential
      to replace conventional anticoagulants in the near future. They include compounds
      that inhibit factor Xa or thrombin.

PMID- 17171592
TI  - New anticoagulants.
AB  - The anticoagulant drugs have an essential role in the prevention and treatment of
      thromboembolic diseases. The currently available anticoagulants have several
      limitations, including a narrow therapeutic window, the risk of bleeding
      complications and, for some drugs, the need for laboratory monitoring and
      parenteral administration. These limitations make the case for the development of
      new anticoagulants. An ideal anticoagulant should be effective, safe, simple to
      use, and widely applicable. The new anticoagulants currently under investigation
      are obtained by molecular technology that makes it possible to target their
      effect toward a selected step of the coagulation cascade. Based on their target,
      new anticoagulants can be classified into three groups: inhibitors of activation
      of coagulation, inhibitors of propagation of coagulation, and inhibitors of
      thrombin formation. Several new anticoagulants currently are in different phases
      of development. Some of them have been approved for clinical use, others are in
      advanced phase of clinical development, and some are still in the initial phase
      of investigation.

PMID- 17171593
TI  - Heparin-induced thrombocytopenia: a review.
AB  - Immune heparin-induced thrombocytopenia (HIT) is a relevant adverse drug reaction
      consisting in a hypercoagulable state caused by an anticoagulant agent. The
      incidence is approximately 6.5% in patients receiving unfractionated heparin
      after orthopedic surgery, and is equal to or lower than 1% in other settings. HIT
      occurrence is a function of heparin type, duration of heparin administration,
      patient population, and gender. The pathogenesis is due to an antibody response
      to the complex heparin/platelet factor 4 in most cases, with secondary activation
      of platelets and coagulation, and finally increased thrombin generation.
      Thrombocytopenia, venous or arterial thrombosis, heparin-induced skin necrosis,
      adrenal hemorrhage, and transient amnesia can characterize the clinical course of
      HIT. Platelet monitoring in patients receiving heparin is indicated to early
      detect HIT. A thrombotic event can be the first manifestation of HIT. Laboratory
      demonstration of heparin-dependent platelet activation confirms the clinical
      diagnosis; antigenic or functional assays are available. Once HIT is highly
      likely or confirmed serologically, immediate heparin cessation is mandatory and
      an alternative therapeutic anticoagulant is needed due to the high risk (or the
      presence) of thrombotic events. The available nonheparin anticoagulants aim to
      reduce thrombin generation. Lepirudin, argatroban, and bivalirudin (direct
      thrombin inhibitors) and danaparoid and fondaparinux (factor Xa inhibitors)
      represent the current treatment options for HIT. Vitamin K antagonists can be
      used safely only after a stable platelet count has been obtained.

PMID- 17171594
TI  - Anticoagulants and cancer survival.
AB  - The association between cancer and activation of blood coagulation has been
      described since Trousseau's time. The hypercoagulable state often encountered in
      cancer patients not only acts as an important risk factor for thrombosis, but
      also may play a role in tumor progression and metastasization. An antineoplastic
      effect of anticoagulants in this setting has often been hypothesized. The results
      of recently conducted clinical trials suggest that cancer patients could have a
      benefit from administration of low molecular weight heparin, particularly in
      those with nonadvanced disease. Additional clinical trials are needed to provide
      an important step forward in this challenging setting.

PMID- 17171595
TI  - Management of the postthrombotic syndrome: the Rotterdam approach.
AB  - The postthrombotic syndrome (PTS) affects the deep venous system, and may also
      extend to the superficial venous system of the legs in patients with a documented
      history of deep vein thrombosis. Clinical symptoms of PTS may vary considerably
      and range from scarcely visible skin changes to changes in pigmentation, pain,
      discomfort, venous ectasia, edema, and ulceration. Our view based on standard
      investigations and the proper place of advanced investigations regarding the
      etiology and pathophysiology of PTS has lead to the Rotterdam approach,
      incorporating the evidence-based diagnostics and treatments available for PTS.
      High-quality duplex sonography is mandatory in all patients, providing anatomical
      and functional (reflux) information on both the deep and superficial venous
      systems, and non- or partially recanalized veins (occlusion) can also be detected
      using this technique. If the results of duplex sonography are not clear or a
      venous desobstruction procedure is to take place, phlebography will be the
      investigation of choice. There is a lot of evidence that medical elastic
      stockings (MECS) are effective in the prevention of PTS with documented reflux,
      obstruction, or both. When prescribing MECS, it is important to examine both
      elasticity and hysteresis of the fabric of the stockings to apply the correct
      dynamic pressure for each individual patient. Patients with documented PTS should
      receive life-long follow-up.

PMID- 17171596
TI  - Diagnosis of pulmonary embolism.
AB  - Conventional pulmonary arteriography for the diagnosis of pulmonary embolism (PE)
      bears several limitations in clinical practice, basically due to its
      invasiveness. On the other hand, no single noninvasive test is both sensitive and
      specific for the diagnosis of PE. Therefore, the choice of available noninvasive
      diagnostic tests guided by the clinical probability of PE is a good compromise at
      present. The first necessary step toward the diagnosis of PE is to raise the
      clinical suspicion, given that no diagnosis can be made if PE is not considered
      in the differential diagnosis of patients with acute cardiorespiratory symptoms.
      Second, empirical or standardized rules for predicting clinical probability may
      be combined with one or more noninvasive tests with the aim of increasing the
      accuracy of the noninvasive diagnosis. The strategy for the noninvasive diagnosis
      of PE varies among different centers according to the availability of each single
      technique that may be integrated with another and according to the
      characteristics of the population that refers to each single center. Therefore,
      spiral CT should not be used as a primary tool for the diagnosis of PE; its role
      needs to be re-evaluated in light of its sensitivity, feasibility, and radiation
      burden on the patients. In patients in whom the diagnosis of PE cannot be made at
      the end of the noninvasive pathway, the use of the invasive techniques must be
      taken into consideration. In our experience, however, such cases should not
      exceed 15 to 20% of the total patient population.

PMID- 17171597
TI  - The value of four-detector row spiral computed tomography for the diagnosis of
      pulmonary embolism.
AB  - Although spiral computed tomography (CT) is being used increasingly as the first
      line imaging procedure in the diagnostic workup of patients with clinically
      suspected pulmonary embolism (PE), the diagnostic value of negative findings, at
      least when using the four-detector row scanners, is still controversial. A total
      of 702 consecutive patients with clinical symptoms suggestive of PE underwent
      four-slice CT. Patients with negative findings received the determination of D
      dimer. Those with positive D-dimer underwent further diagnostic workup to confirm
      or rule out the diagnosis of PE. Those with negative D-dimer were followed-up to
      6 months to detect the development of symptomatic venous thromboembolism (VTE).
      The CT test was interpreted as negative in 536 patients (76.3%). These patients
      had the D-dimer determination, which was positive in 279 and negative in the
      remaining 257 patients. Of the former, PE subsequently was documented in 55
      patients (19.7%). Of the latter, symptomatic VTE in the follow-up period
      developed in three patients (1.17%; 95% confidence interval, 0.24 to 3.38%). In
      conclusion, when using the four-detector row, the negative predictive value of CT
      findings in patients with clinically suspected PE and positive D-dimer is low. In
      contrast, it is safe to withhold anticoagulation from patients with negative
      findings and negative D-dimer.

PMID- 17171598
TI  - Risk stratification of acute pulmonary embolism.
AB  - Acute pulmonary embolism (PE) is a potentially life-threatening condition, with
      an overall 3-month mortality rate of 15% and with right ventricular failure as
      the most common cause of early death. Risk stratification facilitates
      identification of high-risk patients and may be helpful in guiding the initial
      and long-term management. In patients with massive PE and hemodynamic
      instability, rapid risk assessment is paramount and bedside echocardiography and
      multislice chest computed tomography (CT) are useful for identifying patients who
      may benefit from thrombolysis or embolectomy. Cardiac biomarkers, including
      troponin and the natriuretic peptides, are sensitive markers of right ventricular
      function. Low levels of troponin, B-type natriuretic peptide (BNP), and NT
      terminal proBNP are all highly sensitive assays for identifying patients with an
      uneventful clinical course. Multislice chest CT is not only useful to diagnose or
      exclude PE; it also is useful for risk assessment. A right-to-left ventricular
      dimension ratio > 0.9 on the reconstructed CT four-chamber view identifies
      patients at increased risk of early death. This article focuses on risk
      stratification tools, including the clinical examination, electrocardiography,
      echocardiography, cardiac biomarkers, and chest CT.

PMID- 17171599
TI  - Chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease that
      results from obstruction of the major pulmonary arteries by incompletely resolved
      or organized pulmonary emboli that have become incorporated into the pulmonary
      artery wall, eventually causing an increase in pulmonary vascular resistance.
      From 0.1 to 4.0% of patients recovering from acute pulmonary embolism develop
      CTEPH. Without intervention, CTEPH is a progressive and lethal disease for which
      there is no effective medical therapy. Pulmonary endarterectomy (PEA) is the
      treatment of choice. Careful pre- and postoperative management is essential for a
      successful outcome after PEA. Lung transplantation is indicated only in few cases
      when PEA is not feasible. In 1994, we started a program (in Pavia, Italy) in
      which members of a multidisciplinary team work closely with the aim of increasing
      experience in the challenging problems these patients present in the evaluative,
      surgical, and postoperative phases of their care. To date, 134 PEAs have been
      performed. Preoperatively, New York Heart Association (NYHA) class distribution
      was three class II, 56 class III, and 75 class IV patients, respectively; mean
      pulmonary artery pressure and pulmonary vascular resistance values were 47 +/- 13
      mm Hg and 1149 +/- 535 dyn/s/cm (-5), respectively. The overall operative
      mortality has been 9.7% (4.5% in 2004). Survival at 3-month, 1-year, and 3-year
      follow-up was 89.5 +/- 2.6%, 87.8 +/- 2.9%, and 83.3 +/- 3.5%, respectively; this
      last rate was unchanged up to 10 years. After PEA, mean pulmonary artery pressure
      and pulmonary vascular resistance values were 25 +/- 9 mm Hg and 322 +/- 229
      dyn/s/cm (-5), respectively, and these results were stable over time. At the 3
      year follow-up, 94% of patients were in NYHA class I or II and were being treated
      with oral anticoagulants only.

PMID- 17171600
TI  - Acute pulmonary embolism after an earthquake in Japan.
AB  - There have been no reports on acute pulmonary embolism (APE) after earthquakes.
      Our aim was to clarify the actual the occurrence of APE following the 2004 Mid
      Niigata Prefecture earthquake in Japan, and to assess the risk factors for APE
      after the event. We sent questionnaires to 122 hospitals in the Niigata
      Prefecture after the earthquake. Cities, towns, and villages in the prefecture
      were classified into two areas (high evacuee rate area, and low evacuee rate
      area) due to the mean ratio of evacuees to the overall population during 1 week
      immediately after the earthquake. A rate of 5% and higher was encountered for the
      high evacuee rate area and a rate of < 5% was encountered for the low evacuee
      rate area. Ten out-of-hospital cases of APE (seven in the high evacuee rate area
      and three in the low evacuee rate area) were diagnosed within the first month
      after the earthquake. The relative risk of APE was high in the high evacuee rate
      area (13.09; P = 0.0002) and also higher in women (8.55; P = 0.04). All patients
      in the high evacuee rate area had stayed in their automobiles for long periods of
      time, but none had done so in the low evacuee rate area ( P = 0.008).

PMID- 17171601
TI  - [Treating depression: not suited for every physician?].

PMID- 17171602
TI  - [Psychotherapeutic treatment options for bipolar disorders. A review of
      randomized controlled studies].
AB  - BACKGROUND: Until recently research into the efficacy of treatment of bipolar
      disorders focused mainly on the pharmacological treatment. Over the last few
      years more and more research has concentrated on the psychological treatments for
      bipolar disorders. aim To review published, controlled and randomised studies
      dealing with the efficacy of forms of psychotherapeutic treatment for bipolar
      disorders. METHOD: By searching Medline and Embase using the search terms,
      'psychotherapy', 'cognitive (behavioural) therapy', 'family therapy' and
      'psychoeducation' we found eight relevant reports of randomised, controlled
      trials, which described the interventions that were undertaken and recorded the
      relapse rates. RESULTS: The following forms of treatment were investigated:
      Relapse-Prevention Plan, Cognitive Behavioural Therapy, Interpersonal and Social
      Rhythm Therapy, Family-Focused Treatment and Group Psychoeducation. These forms
      of treatment were used in addition to standard pharmacological treatment. The
      addition of psychotherapeutic treatment was found to reduce lower the relapse
      rate, to lead to less hospitalisation and to improve functioning. CONCLUSION: The
      authors recommend that patients with bipolar disorders be offered
      psychotherapeutic treatment because it is likely to lower the risk of relapse.

PMID- 17171603
TI  - [Psychology and psychotherapy in bipolar disorder].
AB  - This essay presents recent insights and theories relating to the various
      psychological mechanisms underlying bipolar disorder and describes a number of
      the psychotherapies that are based on these mechanisms. Each type of
      psychotherapy derives from the assumption that bipolar disorder has a
      neurobiological origin and all the psychotherapies involve long-term
      pharmacotherapy and comprise many psychoeducational elements. The psychotherapies
      complement each other and the best and most useful parts of one therapy can be
      combined with those of others in everyday practice. Patients participating in
      these psychotherapies can obtain additional support from self help manuals.

PMID- 17171604
TI  - [The Multidisciplinary Guideline for Depression: a commentary].
AB  - The multidisciplinary guideline for the treatment of depression has come to be
      regarded as an important summary of the currently available information about the
      treatment of depression. We are critical of several of the views expressed in
      this guideline--first of all, the guideline opts for the selective uptake
      inhibitors fluvoxamine, paroxetine and sertraline rather than for citalopram, and
      secondly, the guideline rates antidepressants more highly than psychotherapy or a
      combination of antidepressants and psychotherapy. There is a lack of cohesion
      between the various aspects of treatment and little attention is given to the
      problems of treating depression in everyday practice. In our view this restricts
      the applicability of the guideline.

PMID- 17171605
TI  - [Limited cohesion of the Multidisciplinary Guideline Depression partly due to
      limited knowledge about different interventions].

PMID- 17171606
TI  - [Reaction to 'Integral psychiatry' and 'Complementary and alternative medicine
      and psychiatry: opinions of patients and psychiatrists'].

PMID- 17171607
TI  - Prediction of the response to chemotherapy in ovarian cancers.
AB  - Ovarian cancer represents the fifth most frequent cause of death as a result of
      malignant processes after cancers of the breast, large intestine, lung and
      stomach. Owing to the localisation of ovarian cancer, approximately 75% of cases
      are diagnosed at the III and IV stages of advancement according to FIGO. Because
      of the advanced stage of the disease surgery has to be followed by chemotherapy
      in most cases of ovarian cancer and therefore resistance to cytostatic drugs
      represents a major clinical problem. The potential to predict the response to
      therapy with the use of cytostatic drugs would enable the most effective drugs to
      be applied in individual cases, thus improving the efficiency of the treatment
      and restricting the development of resistance to cytostatic drugs. In the present
      paper the progress made so far in the prediction of the clinical course of
      ovarian cancer is reviewed. The significance of the expression of the ATP-binding
      cassette (ABC) transporters is described, including P-glycoprotein and MRP2, the
      principal representatives of the protein group. The importance of disturbed
      control of apoptosis and the overexpression of HER-2 and topoisomerase 1A are
      also discussed. Two sections are devoted to the most recent studies in the
      biology of ovarian cancer, pangenomic studies on gene expression using DNA
      microarrays and aberrations of DNA methylation.

PMID- 17171608
TI  - The pathophysiology of intracerebral haemorrhage.
AB  - Spontaneous intracerebral haemorrhage carries a high mortality rate and treatment
      of the disease raises more questions then answers. Mass effect, ischaemia and
      toxicity of blood components are responsible for brain tissue damage. Initially
      occurring disturbances of cerebral blood flow have a temporary character and do
      not play a key role in the pathology of intracerebral haematoma. Oedema
      formatting in the 24-48 hours after intracerebral bleeding is the result of
      multidirectional processes. The pathological mechanism that underlines it is the
      function of activation of systemic complement and cascade of coagulation. In the
      light of these findings, further clinical and experimental investigations should
      be focused on these factors.

PMID- 17171609
TI  - The size of selected human skull foramina in relation to skull capacity.
AB  - An anatomical study was undertaken in order to investigate whether the sizes of
      selected human skull foramina with significant venous compartments correlated
      significantly with skull capacity. A total of 100 macerated human skulls were
      examined to determine the diameter of the foramina and the skull capacity.
      Measurements of the surface area of the foramina were made using a computerised
      digital analysis system. Only the size of the hypoglossal canal and jugular
      foramen were found to correlate significantly with the capacity of the skull.
      This correlation, together with the considerable size of the hypoglossal canal,
      indicated its important role in the venous drainage of the brain. There was
      considerable centralisation of venous outflow from the brain, with 60% of the
      area of all venous foramina of the skull occupied by jugular foramina. Asymmetry
      between the right and left jugular foramina was identified, with an average ratio
      of 1.6 (ranging between 1 and 3.47). In the case of right-sided domination the
      correlation between the skull capacity and the size of both jugular foramina was
      negative (the larger the skull cavity, the less the asymmetry), while in the case
      of left-sided domination the correlation was positive. Perhaps the left-sided
      domination is less advantageous for the haemodynamics of blood outflow, as the
      left brachiocephalic vein is longer and is often compressed by the sternum and
      aortic arch.

PMID- 17171611
TI  - The connection between the papillary muscles and leaflets of the tricuspid valve.
AB  - The tricuspid valve is more differentiated during evolutionary development than
      the mitral valve. In birds it is a muscular structure joined directly to the
      papillary muscles, although the mitral valve of birds resembles that of mammals.
      There have been well-known studies describing the evolutionary line of connection
      of the tricuspid valve with the papillary muscles. The present study was
      performed on a group of 107 formalin-fixed adult human hearts. The valves and
      papillary muscles were classified according to a scheme for human hearts drawn up
      earlier. The types of connection between leaflets of the tricuspid valve and the
      papillary muscles were classified according to a scheme drawn up earlier for
      vertebrates. We observed 3 types of connection between leaflets of the tricuspid
      valve and the papillary muscles in the group studied. The muscular and membranous
      connections were not linked with any one type of tricuspid valve. Atypical forms
      of distribution of the tendinous chords of the right ventricle were observed. It
      was found that valves with a higher number of leaflets were (with the exception
      of type 0) provided with a smaller number of tendinous chords. Atavistic features
      and atypical forms of distribution of the tendinous chords are present in a small
      percentage of samples of the human right valvular apparatus.

PMID- 17171610
TI  - The reproductive toxicity of the organophosphate pesticide 0, 0-dimethyl 0-4
      nitrophenyl phosphorothioate (methyl parathion) in the male rat.
AB  - Methyl parathion (MP) is a pesticide widely used to protect crops but also
      illegally used in many countries for spraying homes and businesses to contain
      insects. The present study was planned to investigate the effects of MP on the
      male reproductive organs in the rat. Male Wistar rats (13-14 weeks old) were
      treated with MP and sacrificed as follows. Experiment 1:0 (water vehicle), 1.75,
      3.5 or 7 mg/kg (i.p.) for 5 days and sacrificed on day 14; experiment 2:0, 0.5 or
      1 mg/kg (i.p.) for 12 days and sacrificed on day 130; experiment 3: 0, 0.5 or 1
      mg/kg (i.p.) for 12 days and sacrificed on day 77; experiment 4: 0, 0.75 or 1.5
      mg/kg (i.p.) for 25 days and sacrificed on day 17; experiment 5: 0 or 3.5 mg/kg
      (p.o.) for 25 days and sacrificed on day 17 after the last exposure. The
      reproductive organs were removed, weighed and processed for histopathological
      analysis. Structural changes, for example the morphology of the epithelium and
      the lumina of the organs, were observed in all animals. Biochemical estimates of
      acid phosphatase (ACP), cholesterol, total protein, uric acid, and vitamin C were
      conducted in the epididymes. The weight of the epididymes increased in experiment
      2 in a dose-dependent pattern (p < 0.01) and decreased in experiments 4 and 5 (p
      < 0.01). The weight of the ductus deferens decreased in experiment 3 at 1 mg/kg
      dose level (p < 0.001) and increased in experiment 5 (p < 0.05). The weight of
      the seminal vesicle decreased in experiment 3 at both 0.5 mg/kg and 1 mg/kg dose
      levels (p < 0.001), and increased in experiment 5 (p < 0.01). The weight of the
      prostate decreased in experiments 4 (in a dose-dependent pattern) and 5 (p <
      0.001). ACP levels decreased in experiment 4 (p < 0.001) with a greater effect at
      0.5 mg/kg than at 1 mg/kg. In experiment 5 (p < 0.01) cholesterol levels
      decreased to less than 50% of the control level for this experiment (p < 0.01)
      and protein levels also decreased (p < 0.01). Vitamin C levels decreased in a
      dose-dependent pattern in experiments 4 (p < 0.001) and 5 (p < 0.01). There were
      no effects on uric acid level. Sperm density was decreased in the epididymes of
      the rats treated and the epithelium of the epididymis and ductus deferens showed
      cellular necrosis, brush-border disruption and nuclear pyknosis. Nuclei were
      haloed, except in experiment 2 and the 0.5 mg/kg group of experiment 3. Methyl
      parathion did not induce significant changes in the structure of the seminal
      vesicle and prostate, except that epithelial folding was shorter than in the
      control. In conclusion, MP is a reproductive toxicant in the male rat and causes
      deterioration in the structural integrity of the reproductive organs and also the
      biochemical parameters in the epididymis.

PMID- 17171612
TI  - A contribution to the discussion concerning the variability of the third peroneal
      muscle: an anatomical analysis on the basis of foetal material.
AB  - The aim of the work was to make a systemic study of the variability of the human
      musculus peroneus tertius during the foetal period. Examination was made of 193
      foetuses of ages ranging from 84 to 256 days after conception. The results
      obtained indicated that the musculus peroneus tertius was present in 83.16% of
      the human foetuses studied and that its intrauterine development was progressive
      and almost proportional. Previous studies have not revealed dimorphic or
      bilateral differences with respect to any of the features examined. On the basis
      of the examinations and bibliographical data a uniform typology of the musculus
      peroneus tertius variants was created and three final types were distinguished:
      the pithecogenic (44% cases), eugenic (34% cases) and progenic (22% cases).

PMID- 17171613
TI  - Identification of greater occipital nerve landmarks for the treatment of
      occipital neuralgia.
AB  - Important structures involved in the pathogenesis of occipital headache include
      the aponeurotic attachments of the trapezius and semispinalis capitis muscles to
      the occipital bone. The greater occipital nerve (GON) can become entrapped as it
      passes through these aponeuroses, causing symptoms of occipital neuralgia. The
      aim of this study was to identify topographic landmarks for accurate
      identification of GON, which might facilitate its anaesthetic blockade. The
      course and distribution of GON and its relation to the aponeuroses of the
      trapezius and semispinalis capitis were examined in 100 formalin-fixed adult
      cadavers. In addition, the relative position of the nerve on a horizontal line
      between the external occipital protuberance and the mastoid process, as well as
      between the mastoid processes was measured. The greater occipital nerve was found
      bilaterally in all specimens. It was located at a mean distance of 3.8 cm (range
      1.5-7.5 cm) lateral to a vertical line through the external occipital
      protuberance and the spinous processes of the cervical vertebrae 2-7. It was also
      located approximately 41% of the distance along the intermastoid line (medial to
      a mastoid process) and 22% of the distance between the external occipital
      protuberance and the mastoid process. The location of GON for anaesthesia or any
      other neurosurgical procedure has been established as one thumb's breadth lateral
      to the external occipital protuberance (2 cm laterally) and approximately at the
      base of the thumb nail (2 cm inferior). This is the first study proposing the use
      of landmarks in relation to anthropometric measurements. On the basis of these
      observations we propose a target zone for local anaesthetic injection that is
      based on easily identifiable landmarks and suggest that injection at this target
      point could be of benefit in the relief of occipital neuralgia.

PMID- 17171614
TI  - The influence of acute and chronic open-field exposure on the hippocampal
      formation: an immunohistochemical study.
AB  - The hippocampus plays a role in new learning, memory and emotion and is a
      component of the neuroanatomical stress circuit. The structure is involved in
      terminating hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress
      and attenuates stress responses by shutting off this axis. The immunoreactivity (
      ir) of c-Fos, NGF and its receptor TrkA following acute and chronic open-field
      stress were studied in CA1-CA3 and the DG of the hippocampus. The material
      consisted of 21 male adult rats divided into three groups: nonstressed (control)
      animals and rats exposed to acute (15 min once) and chronic (15 min daily for 21
      days) aversive stimulation (open-field exposure). The brains were stained with
      use of immunohistochemical methods for c-Fos, NGF or TrkA. In the animals exposed
      to acute open-field stress the number of c-Fos-, TrkA and NGF-ir cells was higher
      in all the structures studied than in the control animals. However they were
      differentiated only in c-Fos immunoreactivity. In the rats exposed to chronic
      open-field stress the number of c-Fos-ir cells in the structures of the
      hippocampal formation studied was smaller than in rats exposed to acute stress
      and was comparable to that in the control group. No differences were observed
      between the groups exposed to acute and chronic stress in the number of TrkA-ir
      cells in the structures under investigation. The number of NGF-ir neurons in CA1
      and CA2 was lower after exposure to chronic than after exposure to acute stress
      but was still higher than that in the control group. Our findings indicate that
      neurons of CA1-CA3 and the DG are engaged in the stress response after acute as
      well as chronic open-field exposure. This is probably related to the important
      role of the hippocampus in processing new spatial information as well as in the
      habituation processes, although these appear to have different mechanisms.

PMID- 17171615
TI  - The neuronal structure of the dorsal nucleus of the lateral geniculate body in
      the common shrew (Sorex araneus) and the bank vole (Clethrionomys glareolus):
      Golgi and Nissl studies.
AB  - The topography and neuronal structure of the dorsal nucleus of the lateral
      geniculate body (GLd) of the common shrew and the bank vole are similar. The
      lateral geniculate body of both the species examined has a homogeneous structure
      and no observable cytoarchitectonic lamination. On the basis of the shape of the
      dendritic arbours as well as the pattern of dendritic arborisations the following
      two types of neurons were distinguished. Type I "bushy" neurons that have
      multipolar or round perikarya (common shrew perikarya 9-12 microm, bank vole
      perikarya 10-13 microm), with 4-6 short thick dendritic trunks that subdivide
      into many bush-like branches. The dendritic trunks are smooth, in contrast to the
      distal branches, which are covered with numerous spine-like protrusions of
      different lengths and forms. An axon emerges from the soma, sometimes very close
      to one of the primary dendrites. The type I neurons are typically projection
      cells that send their axons to the primary visual cortex. These neurons
      predominate in the GLd of both species. Type II neurons, which have an elongated
      soma with primary dendrites arising from opposite poles of the perikaryon (common
      shrew perikarya 8-10 microm, bank vole perikarya 9-11 microm). The dendritic
      arbours of these cells are less extensive and their dendrites have fewer spines
      than those of the type I neurons. Axons were seldom observed. The type II neurons
      are presumably interneurons and are definitely less numerous than the type I
      neurons.

PMID- 17171616
TI  - Fluoride alters type I collagen expression in the early stages of odontogenesis.
AB  - Fluoride alters the expression and post-translational modifications of
      extracellular matrix proteins in dentin. The aim of our study was to determine
      the effects of fluoride on type I collagen expression during the early stages of
      tooth germ development in rats. Pregnant dams were divided into three groups and
      fed a standard diet. From the fifth day of pregnancy the three groups received
      tap water with, respectively, trace amounts of fluoride (C), a low fluoride
      concentration (FL) or and a high fluoride concentration (FH). Changes in type I
      collagen expression and distribution were evaluated. The expression of type I
      collagen was restricted to the extracellular spaces of cells of mesenchymal
      origin. In the youngest animals the most intense immunoreactivity for type I
      collagen was detected in predentin of the FL group. Although the intensity of
      immunostaining increased in proportion to the age of the animals, the largest
      increase in the groups investigated was detected in the FL group. We concluded
      that a low concentration of fluoride can act as a stimulator of type I collagen
      deposition in the extracellular matrix of dentin, while high concentrations of
      fluoride have an opposite effect, acting as an inhibitor of type I collagen
      formation in dentin.

PMID- 17171617
TI  - The neuronal structure of the preoptic area in the mole and the rabbit: Golgi and
      Nissl studies.
AB  - The present studies were carried out on the brains of the adult mole and rabbit.
      The preparations were made by means of the Golgi technique and the Nissl method.
      Two types of neurons were distinguished in the preoptic area (POA) of both
      species: bipolar and multipolar. The bipolar neurons have oval, fusiform or round
      perikarya and two dendritic trunks arising from the opposite poles of the cell
      body. The dendrites bifurcate once or twice. The dendritic branches have
      swellings, single spine-like and filiform processes. The multipolar neurons
      usually have triangular and quadrangular perikarya and from 3 to 5 dendritic
      trunks. The dendrites of the mole neurons branch sparsely, whereas the dendrites
      of the rabbit neurons display 2 or 3 divisions. On the dendritic branches
      varicosities and different protuberances were observed. The general morphology of
      the bipolar and multipolar neurons is similar in the mammals studied, although
      the neurons of the rabbit POA display a more complicated structure. Their
      dendritic branches show more divisions and possess more swellings and different
      processes than the dendrites of the neurons of the mole POA. Furthermore, of the
      multipolar neurons only the dendrites in POA of the rabbit were observed to have
      a rosary-like beaded appearance.

PMID- 17171618
TI  - Does a third head of the rectus femoris muscle exist?
AB  - Current anatomical texts describe only two tendinous origins of the rectus
      femoris muscle. The authors identified one older reference in which a third head
      of the rectus femoris muscle was briefly described. In order to confirm the
      existence of this head, 48 adult cadavers (96 sides) underwent detailed
      dissection of the proximal attachments of the rectus femoris muscle. Of these
      sides 83% were found to harbour a recognised third head of the rectus femoris
      muscle. This additional head was found to attach deeply to the iliofemoral
      ligament and superficially with the tendon of the gluteus minimus muscle as it
      attached into the femur. This tendon attached to the anterior aspect of the
      greater trochanter in an inferolateral direction compared to the straight head.
      The mean length and width of the third head was 2 cm and 4 cm, respectively. The
      mean thickness was found to be 3 mm. Most commonly this third head was
      bilaterally absent or bilaterally present. However, 4.2% were found only on left
      sides and 5.2% were found only on right sides. The angle created between the
      reflected and third heads was approximately 60 degrees. Two sides (both left
      sides with one female and one male specimen) were found to have third heads that
      were bilaminar. These bilaminar third heads had a distinct layer attaching to the
      underlying iliofemoral ligament and a superficial layer blending with the gluteus
      minimus tendon to insert onto the greater trochanter. Although the function of
      such an attachment is speculative, the clinician may wish to consider this
      structure in the interpretation of imaging or in surgical procedures in this
      region, as in our study it was present on the majority of sides.

PMID- 17171619
TI  - A study on the morphology of the popliteus muscle and arcuate popliteal ligament.
AB  - The aim of this study was to investigate the origins and morphological features
      of the popliteus muscle in cadavers. In a sample of 40 lower limbs taken from
      cadavers the exact morphological features of the popliteus muscle were examined.
      In 100% of the cases studied we noticed, apart from the known femoral origin from
      the lateral femoral epicondyle, a fibular origin from the styloid process of the
      head of the fibula directed obliquely and blending with the main femoral origin,
      forming the arms of a Y-shaped structure. In all the cases a capsular origin was
      presented, while in 91.67% an origin lateral to it from the superior border of
      the posterior horn of the lateral meniscus was found. The capsular and meniscal
      origins formed the base of the Y-shaped structure that corresponded to the known
      arcuate ligament. We consider that the additional origins of the popliteus muscle
      form the arcuate ligament, which is not a distinct anatomical structure as it is
      described in traditional anatomical textbooks. In addition, we have analysed the
      exact morphological features of the capsular, fibular and meniscal origins of the
      popliteal muscle.

PMID- 17171620
TI  - Basic axes of human heart in correlation with heart mass and right ventricular
      wall thickness.
AB  - A comparison of the data published in anatomy textbooks and anthropological
      tables does not reveal any change in basic heart dimensions during the period
      since the beginning of the 20th century to nowadays. However, normal values of
      many other parameters have changed up to 30% over the same period. These changes
      may be caused by the acceleration phenomenon or the extension of average
      lifespan. The progress of laboratory medicine methodology permitted the
      introduction of new biochemical tests in myocardial infarct diagnosis, such as
      myoglobin and troponins T and I measurement, as well as better understanding of
      cardiac metabolism. Parameters describing the direction and intensity of
      metabolic changes are substrate extraction and metabolic equilibrium. The
      expression describing metabolic equilibrium contains heart mass value. Therefore,
      as studying heart mass in vivo is not possible, it may be important to study it
      in vitro. The study was performed on a group of 107 formalin-fixed human hearts.
      The organs came from adults of both sexes: 30 women and 77 men, aged 18 to 90
      years. None of the hearts carried signs of macroscopic developmental
      abnormalities or pathologic changes.

PMID- 17171621
TI  - Malignant fibrous histiocytoma of the spermatic cord: a case report and review of
      the literature.
AB  - Malignant fibrous histiocytoma (MFH) is a morphologically ill-defined tumour of
      the soft tissues and may involve nearly every organ of the body. MFH of the
      spermatic cord represents an extremely rare entity and reports of it in the
      literature are limited. We report a 69-year-old man found to have a left
      spermatic cord MFH and retroperitoneal and mediastinal lymphadenopathy, who was
      treated with radical orchiectomy and adjuvant chemotherapy. The morphological
      findings of the spermatic tumour are presented and the literature is reviewed to
      clarify the potential diagnostic/therapeutic approaches and the prognosis related
      to spermatic cord MFH.

PMID- 17171622
TI  - An atypical position of the foramen ovale.
AB  - Visual inspection of a dry adult human skull revealed absence of a typical
      foramen ovale on the left side of the cranial base. The region of the foramen
      ovale was covered by an osseous lamina, which was continuous with the lateral
      pterygoid plate and thus formed a wall of an apparent canal, which opened on the
      lateral side of the pterygoid process. This canal is referred to as an oval canal
      (canalis ovalis), instead of the foramen ovale. It runs superiorly, medially from
      the infratemporal fossa, and opens into the middle cranial fossa. The altered
      osseous morphology of this basicranial region may affect the course of the
      neurovascular structures which pass through the foramen ovale. As a consequence,
      clinical symptoms could occur, including paresthesiae of the inner aspect of the
      cheek and compression and neuralgia of the mandibular nerve or its branches.

PMID- 17171623
TI  - High origin of a superficial ulnar artery arising from the axillary artery:
      anatomy, embryology, clinical significance and a review of the literature.
AB  - The superficial ulnar artery (SUA) is an ulnar artery of high origin that lies
      superficially in the forearm. Its reported frequency ranges from 0.17% to 2%.
      During anatomical dissection in our department we observed a unilateral case of
      SUA in a 75-year-old white male human cadaver. It originated from the right
      axillary artery at the level of the junction of the two median nerve roots and
      followed a looping course, crossing over the lateral root of the median nerve and
      running lateral to it in the upper and middle thirds of the arm, whereas in the
      inferior third of the arm the SUA crossed over the median nerve and ran medially
      to it. In the cubital fossa, it passed superficially over the medial side of the
      ulnar aponeurosis and coursed subcutaneously in the ulnar side of the forearm
      superficially to the forearm flexor muscles. In the hand the SUA anastomosed with
      the superficial palmar branch of the radial artery, creating the superficial
      palmar arch. Additionally, it participated in the development of the deep palmar
      arch. The axillary artery, after the origin of the SUA, continued as the brachial
      artery and divided into the radial and common interosseous arteries in the
      cubital fossa. The normal ulnar artery was absent. No muscular or other arterial
      variations were observed in this cadaver. The embryological interpretation of
      this variation is difficult and it may arise as a result of modifications to the
      normal pattern of capillary vessel maintenance and regression. The existence of a
      SUA is undoubtedly of interest to the clinician as well as to the anatomist. This
      report presents a case of unilateral SUA along with a review of the literature,
      embryological explanation and analysis of its clinical significance.

PMID- 17171624
TI  - A complex variation in the superficial palmar arch.
AB  - In this article we describe a unique and complex variation in the arterial
      pattern of the left hand of a female cadaver. The following variations were found
      in this case: a) persistent median artery of the palmar type, terminating in the
      hand as the princeps pollicis and radialis indicis arteries; b) the ulnar artery
      giving only two common palmar digital arteries; c) the second digital palmar
      artery without division into two digital branches and instead supplying only the
      radial side of the ring finger; d) absence of the first common digital artery
      with the contiguous sides of the second web space supplied by the first palmar
      metacarpal artery from the deep palmar arch; e) early bifurcation of the median
      nerve proximal to the flexor retinaculum.

PMID- 17171625
TI  - An unusual course of the radial artery.
AB  - Radial artery variations are of importance for clinicians, whether in
      angiographic examinations or surgical approaches. The high origin radial artery
      is the most frequent arterial variation observed in the upper limb, showing an
      incidence of 14.27% in dissection material and 9.75% in angiographic examination.
      In the present study an unusual course of the radial artery and its relation with
      the median nerve has been evaluated. During embryological development the radial
      artery sprouts from two arterial buds arising from the lateral side of the
      brachial artery and coalescing with each other. The artery lies in the forearm
      and is overlapped by the brachioradial muscle. In this particular case the radial
      artery originated from the medial side of the brachial artery and crossed the
      median nerve twice in an unusual manner 8 cm below the point at which the deep
      brachial artery arose and 12 cm above the intercondylar line. These results will
      enhance anatomical knowledge of the region and reduce complication in surgical
      approaches.

PMID- 17171626
TI  - The technique of inhalation anaethesia in experimental investigation in the rat.
AB  - The rat is the most frequently used animal in scientific inquiry conducted for
      the purpose of advancing basic knowledge that may lead to an improvement in the
      results of treatment. Understanding of the pharmacological properties of
      inhalation anaesthetics, in combination with monitoring of their concentration in
      the inspired and end-tidal gas, together provide safe and precise control of the
      depth of the anaesthesia. However, accurate application of the inhalation method
      of anaesthesia requires special equipment for the delivery and effective
      scavenging of inhalation anaesthetics.

PMID- 17171627
TI  - Frontomaxillary facial angle at 11+0 to 13+6 weeks' gestation-reproducibility of
      measurements.
AB  - OBJECTIVE: To assess the intra- and interobserver reproducibility in the
      measurement of the frontomaxillary facial (FMF) angle at 11+0 to 13+6 weeks'
      gestation and to investigate the effect of deviations from the exact mid-sagittal
      view on these measurements. METHODS: Three-dimensional (3D) volumes of the fetal
      face were used by two operators to measure the FMF angle in 50 chromosomally
      normal and 50 trisomy 21 fetuses. The measurements were taken in the exact mid
      sagittal view and repeated after lateral rotation of the head by 5 degrees, 10
      degrees and 15 degrees away from the vertical position of the occipitofrontal
      diameter axis. Mean difference and 95% limits of agreement between paired
      measurements of FMF angle by the same and by two different sonographers were
      determined. RESULTS: In the mid-sagittal plane the maxillary bone was rectangular
      shaped. Rotation away from this plane became easily recognizable because at a
      mean of 7 degrees (range, 4-10 degrees) the shape of the maxilla changed with the
      appearance of the zygomatic process of the maxilla and at a mean of 8 degrees
      (range, 4-12 degrees) the tip of the nose became invisible. In both the normal
      and trisomy 21 fetuses the FMF angle measured at 5-15 degrees was not
      significantly different from the one measured in the mid-sagittal plane. In 95%
      of the cases, the difference between paired measurements of the FMF angle by the
      same sonographer at the mid-sagittal plane was between -2.3 degrees and 3.0
      degrees and at 15 degrees it was -1.0 degrees to 6.8 degrees. At the mid-sagittal
      plane, the difference in measurements between two sonographers was -3.1 to 3.0
      degrees. CONCLUSION: The landmarks that define the mid-sagittal plane of the
      fetal face are the tip of the nose and the rectangular shaped maxilla.
      Measurement of the FMF angle is highly reproducible.

PMID- 17171628
TI  - Comparison of CT- or ultrasound-guided drainage with concomitant intravenous
      antibiotics vs. intravenous antibiotics alone in the management of tubo-ovarian
      abscesses.
AB  - OBJECTIVE: The purpose of this study was to compare the outcome of treatment of
      tubo-ovarian abscesses by imaging-guided drainage and antibiotics vs. intravenous
      antibiotics alone. METHODS: A retrospective chart review of all patients
      hospitalized with a diagnosis of tubo-ovarian abscess was performed. Patients
      were categorized into two groups. The first group consisted of subjects treated
      with intravenous antibiotics alone. Patients in the second group had primary
      image-guided drainage with concomitant intravenous antibiotics. Treatment
      failures in the primary antibiotics group underwent salvage drainage when
      feasible. The primary outcome of interest was complete response. Secondary
      outcomes included need for additional treatment, duration of resolution of fever,
      total length of hospital stay, and complication rates. We also evaluated the
      effectiveness of secondary drainage in patients who failed primary antibiotic
      therapy alone. RESULTS: A total of 58 patients were included in the study. Fifty
      patients were treated primarily with intravenous antibiotics; eight patients had
      primary drainage, which was guided by ultrasound in all cases. Complete response
      was noted in 29 (58%) patients treated with antibiotics alone. All eight (100%)
      patients in the primary drainage group responded to treatment. Of the 21
      treatment failures with primary antibiotics, two underwent surgery and 19 (90.5%)
      had salvage drainage with either ultrasound or computed tomographic guidance; 18
      of 19 salvage drainages led to complete recovery. Subjects in the primary
      drainage group required shorter hospital stays and showed more rapid resolution
      of fever. No significant morbidity was noted as a consequence of drainage
      procedures. A higher failure rate for secondary drainage was noted in older
      patients, those with larger tubo-ovarian abscesses, and those with a history of
      pelvic inflammatory disease. CONCLUSION: Drainage of tubo-ovarian abscesses with
      concomitant intravenous antibiotics is an effective and safe treatment for the
      primary or secondary treatment of tubo-ovarian abscesses.

PMID- 17171629
TI  - Short cervix: is a follow-up measurement useful?
AB  - OBJECTIVE: To study if a repeat cervical length (CL) measurement in the patient
      already diagnosed with a short cervix has any additional value in the prediction
      of preterm delivery. STUDY DESIGN: This was a retrospective study of singleton
      pregnancies with cervical lengths 1-25 mm at a gestational age of 16-28 weeks
      seen in our institution between 2002 and 2005. Patients who were managed
      expectantly and had a follow-up CL measurement within 3 weeks were included.
      Delivery data were obtained from the patients' computerized medical records.
      RESULTS: Sixty-eight patients met the inclusion criteria. 37% of the patients had
      a shorter CL on the second measurement. These patients delivered at an earlier
      gestational age (36+4 vs. 38+2 weeks, P=0.031) and were more likely to deliver at
      <37 weeks (60% vs. 26%, P=0.009). The change in the CL correlated with earlier
      gestational age at delivery and delivery at <37 weeks. CONCLUSION: In patients
      diagnosed with a short cervix, follow-up CL measurement is a strong predictor of
      preterm delivery. Greater change in the CL correlates with an earlier gestational
      age at delivery. In the patient diagnosed with a short cervix, a repeat
      measurement of CL gives additional predictive value.

PMID- 17171630
TI  - Histomorphometric features of hydatidiform moles in early pregnancy: relationship
      to detectability by ultrasound examination.
AB  - OBJECTIVE: The majority of partial (PHM) and complete (CHM) hydatidiform moles
      are diagnosed in early pregnancy. About half are identified as molar on
      ultrasonographic examination prior to evacuation. It is uncertain whether
      unsuspected cases represent an intrinsically different molar phenotype or are
      simply dependant on sonographer expertise. We measured a microscopic parameter,
      average villus diameter, of evacuated PHMs and CHMs to ascertain the cause of non
      detection on ultrasound. METHODS: Fifty-four molar pregnancies were examined from
      the files of the Trophoblastic Disease Unit, in which results of an ultrasound
      examination prior to evacuation were known. In each, the average cross-sectional
      diameter of the largest 10 villi was recorded. Maximum villus diameters were
      compared between gestational age groups (<14 weeks and >or=14 weeks), and
      ultrasound detection groups (detected (d) and not detected (nd)). RESULTS: The
      average maximum villus diameter of the largest hydropic villi was significantly
      less in the first trimester for both PHMs and CHMs that were undetected by
      ultrasound examination compared to those identified as molar sonographically
      (P<0.001 and P<0.001, respectively). There was no significant difference in the
      maximum villus diameter between PHMs and CHMs that were not detected
      sonographically in the first trimester (P=0.44). Beyond 14 weeks of gestation,
      there was no significant difference between PHMs detected and undetected
      sonographically (P=0.88). CONCLUSION: The average diameter of the largest, most
      hydropic villi, is significantly greater in cases of PHMs and CHMs detected by
      ultrasound examination in the first trimester compared to that of those not
      detected sonographically, but beyond 14 weeks such differences are minimal. These
      findings suggest that, although sonographer expertise could potentially increase
      ultrasound detection rates somewhat for PHMs and CHMs, a significant proportion
      of cases demonstrate minimal hydropic change in the first trimester and are
      therefore likely to remain unidentifiable by ultrasound examination prior to
      evacuation, even with improved sonographer expertise.

PMID- 17171631
TI  - Nomograms of the axial fetal cerebellar hemisphere circumference and area
      throughout gestation.
AB  - OBJECTIVE: The widely applied transcerebellar diameter (TCD) obtained at axial
      cranial imaging, measures the distance between the lateral aspects of the
      cerebellum and incorporates the width of the cerebellar vermis. Our objective was
      to create reference ranges of axial fetal cerebellar hemisphere circumference
      (CHC) and area (CHA), independent of the cerebellar vermis, throughout gestation.
      METHODS: This cross-sectional study involved pregnant patients between 14 and 41
      weeks of gestation. Inclusion criteria consisted of well-established dates
      (confirmed by early ultrasound), non-anomalous singleton fetuses and intact
      amniotic membranes. Sonographic measurements included biparietal diameter (BPD),
      head circumference (HC), abdominal circumference (AC), femur length (FL), humerus
      length (HL), TCD, and estimated fetal weight (EFW). Values of axial fetal CHC and
      CHA were each calculated as the mean of three separate measurements. The 5th,
      50th and 95th centiles were estimated at each week of gestational age (GA) by
      least-squares regression for the mean and standard deviation (SD) of the CHC and
      CHA as functions of GA. r2 and associated P-values for the relationships of CHC
      and CHA with other sonographic biometric measurements were calculated. RESULTS:
      The study included 651 consecutive patients. All attempts at obtaining axial
      fetal CHC and CHA were successful. Mean maternal age was 27.3+/-6.7 years, median
      gravidity was 1 (range 1-16), and median parity was 1 (range 0-6). Mean CHC (cm)
      throughout gestation was modeled as -2.091+0.2563xGA (weeks) (SD=
      0.075+0.0164xGA), and mean CHA (cm2) was modeled as 0.245-0.0765xGA+0.00506xGA2
      (SD=1.167-0.1565xGA+0.006785xGA(2)-0.00008028xGA3). Fetal axial CHC and CHA
      correlated significantly and strongly with BPD, HC, AC, HL, FL, TCD and EFW (all
      R2 values were >or=0.95, and all P-values were <0.001). CONCLUSION: Nomograms of
      axial fetal cerebellar hemisphere circumference and area throughout gestation,
      independent of the cerebellar vermis, have been provided.

PMID- 17171632
TI  - First-trimester combined screening for trisomy 21 in a predominantly Chinese
      population.
AB  - OBJECTIVE: To examine the effectiveness of first-trimester fetal trisomy 21
      screening using a combination of maternal age, nuchal translucency thickness (NT)
      and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and
      pregnancy-associated plasma protein-A (PAPP-A) levels in a predominantly Chinese
      population in Hong Kong. METHODS: This was a prospective study over a 1.5-year
      period of 2990 women who underwent combined screening for trisomy 21 between 11+0
      and 13+6 weeks of gestation in a university fetal medicine unit. NT was measured
      according to the criteria set by The Fetal Medicine Foundation (FMF), maternal
      serum free beta-hCG and PAPP-A levels were measured, and the risk of trisomy 21
      was calculated using The FMF's algorithm. Fetal karyotyping was advised when the
      risk was 1 : 300 or above. All subjects were followed up for pregnancy and fetal
      outcome. RESULTS: Of the 2990 women who underwent the screening program, 99% were
      Chinese. There were 57 twin pregnancies, giving a total of 3047 fetuses. Thirty
      one percent of the women were 35 years old or above. One hundred and eighty-five
      (6.1%) fetuses were screen-positive; this included 14 cases of trisomy 21 and 17
      cases of other chromosomal abnormalities. The positive predictive value was
      16.7%. Among the 2862 screen-negative fetuses, only 18 (0.6%) cases had an
      unknown fetal outcome. There were no cases in which trisomy 21 was missed and the
      infant was liveborn. CONCLUSION: First-trimester combined screening for fetal
      trisomy 21 is highly effective among Chinese subjects.

PMID- 17171634
TI  - In vitro multipotentiality and characterization of human unfractured traumatic
      hemarthrosis-derived progenitor cells: A potential cell source for tissue repair.
AB  - Mesenchymal progenitor cells (MPCs) are a very attractive tool in the context of
      repair and regeneration of musculoskeletal tissue damaged by trauma. The most
      common source of MPCs to date has been the bone marrow, but aspirating bone
      marrow from the patient is an invasive procedure. In an attempt to search for
      alternative sources of MPCs that could be obtained with minimal invasion, we
      looked into traumatic hemarthrosis of the knee. In this study, we determined
      whether a population of multipotent MPCs could be isolated from acute traumatic
      knee hemarthrosis in the absence of intra-articular fractures. Mononuclear cells
      were isolated from the aspirated hemarthrosis by density gradient separation, and
      cultured. We were able to obtain plastic adherent fibroblast-like cells from the
      mononuclear cell fractions. Flow cytometry analysis revealed that the adherent
      fibroblast-like cells were consistently positive for CD29, CD44, CD105, and
      CD166, and were negative for CD14, CD34, and CD45. These were similar to control
      bone marrow stromal cells. These cells could differentiate in vitro into
      osteogenic, adipogenic, and chondrogenic cells in the presence of lineage
      specific induction factors. In conclusion, acute unfractured traumatic
      hemarthrosis of the knee contains MPCs with multipotentiality. Because knee
      hemarthrosis is easy to harvest with minimal pain and without unnecessary
      invasion, we regard hemarthrosis-derived cells as an additional progenitor cell
      source for future tissue engineering and cell-based therapy in knee injuries.

PMID- 17171635
TI  - Mitotic control of RUNX2 phosphorylation by both CDK1/cyclin B kinase and
      PP1/PP2A phosphatase in osteoblastic cells.
AB  - Skeletal development and osteoblast maturation require the phenotype promoting
      activity of the transcription factor RUNX2, which controls both cell growth and
      differentiation in osteoblasts. We have recently shown that in actively
      proliferating cells RUNX2 regulates the expression of specific target genes as
      cells enter and exit mitosis. In this study, we addressed whether post
      translational modifications of RUNX2 control its activity during mitotic exit.
      Western blot analysis of proteins from osteoblastic Saos-2 cells released from
      mitotic inhibition into early G(1) show a phosphatase-sensitive shift in the
      mobility of RUNX2 in SDS gels. The slowly migrating hyper-phosphorylated form of
      RUNX2 is immunoreactive with a CDK related phospho-antibody (MPM2) only in
      mitotic cells and is converted into a faster migrating hypo-phosphorylated RUNX2
      when cells complete mitosis. This conversion is inhibited by okadaic acid, an
      inhibitor of protein phosphatases 1 and 2 (PP1 and PP2A), but not by deltamethrin
      which blocks PP2B phosphatase. Mitotic phosphorylation of RUNX2 is sensitive to
      the CDK inhibitors roscovitine and olomoucine. Furthermore, RUNX2 can directly
      interact with CDK1 and is phosphorylated in vitro by the CDK1/cyclin B kinase
      complex. Hence, RUNX2 is hyper-phosphorylated by CDK1/cyclin B during mitosis,
      and dynamically converted into a hypo-phosphorylated form by PP1/PP2A-dependent
      dephosphorylation after mitosis to support the post-mitotic regulation of RUNX2
      target genes.

PMID- 17171636
TI  - Microenvironmental influences in melanoma progression.
AB  - An often overlooked facet of tumor biology research is the involvement of the
      surrounding tumor microenvironment. Increasing evidence is being presented to
      support a major role for stromal components in all stages of tumorigenesis
      including initiation, progression, and metastasis. Melanoma serves as a model for
      studying cellular and stromal interactions within the tumor microenvironment due
      to the array of cell types localized to these lesions. Here, we discuss the both
      the molecular mechanisms, as well as the extracellular and contextual input that
      contribute to melanoma progression. Special emphasis is given to the assorted
      cell types and their interactions with the extracellular matrix and adjacent
      cells. Melanoma progression also initiates development of intralesional hypoxic
      regions; the relative significance of hypoxia in disease is also addressed.
      Lastly, a number of laboratories are currently developing innovative strategies
      to study melanoma within a microenvironmental platform. These promising model
      systems and their potential for closing current gaps in knowledge of disease are
      reviewed. The development of such models holds translational value that cannot be
      achieved with most current systems.

PMID- 17171637
TI  - Benzyl butyl phthalate influences actin distribution and cell proliferation in
      rat Py1a osteoblasts.
AB  - We previously reported that transient administration of phthalates induced actin
      cytoskeleton disruption in Py1a osteoblasts. However, the mechanism of this
      transient effect was not elucidated. In this study we provided evidence that the
      actin cytoskeletal re-established conditions are dependent on new actin
      expression and synthesis. To assess the role of phthalates in modulating the
      distribution of actin, confocal and electron microscopy studies were carried out.
      Results indicated a modification of actin distribution after phthalate
      administration. In addition, a relation with the nucleoskeletal component lamin A
      supports the hypothesis that phthalates may participate in regulatory cell
      processes involving actin in Py1a osteoblasts. The present study also supports
      the mitogenic effects of phthalates, which involve microfilament disruption,
      nuclear actin and lamin A. In particular, the increased levels of cyclin D3,
      which in mammalian cells plays a critical role in G1 to S transition and is a
      putative proto-oncogene in benzyl butyl phthalate treated cells, suggested a
      possible effect of the endocrine disruptor in cancer processes.

PMID- 17171638
TI  - Curcumin-induced GADD153 upregulation: modulation by glutathione.
AB  - As we reported previously, GADD153 is upregulated in colon cancer cells exposed
      to curcumin. In the present study, we ascertained the involvement of glutathione
      and certain sulfhydryl enzymes associated with signal transduction in mediating
      the effect of curcumin on GADD153. Curcumin-induced GADD153 gene upregulation was
      attenuated by reduced glutathione (GSH) or N-acetylcysteine (NAC) and potentiated
      by the glutathione synthesis inhibitor, L-buthionine-(S,R)-sulfoximine (BSO).
      Additionally, GSH and NAC decreased the intracellular content of curcumin.
      Conversely, curcumin decreased intracellular glutathione and also increased the
      formation of reactive oxygen species (ROS) in cells, but either GSH or NAC
      prevented both of these effects of curcumin. In affecting the thiol redox status,
      curcumin caused activation of certain sulfhydryl enzymes involved in signal
      transduction linked to GADD153 expression. Curcumin increased the expression of
      the phosphorylated forms of PTK, PDK1, and PKC-delta, which was attenuated by
      either GSH or NAC and potentiated by BSO. Furthermore, selective inhibitors of
      PI3K and PKC-delta attenuated curcumin-induced GADD153 upregulation.
      Collectively, these findings suggest that a regulatory thiol redox-sensitive
      signaling cascade exists in the molecular pathway leading to induction of GADD153
      expression as caused by curcumin.

PMID- 17171639
TI  - Centrosomal localization of DNA damage checkpoint proteins.
AB  - During mitosis, the phosphatidylinositol-3 (PI-3) family-related DNA damage
      checkpoint kinases ATM and ATR were found on the centrosomes of human cells.
      ATRIP, an interaction partner of ATR, as well as Chk1 and Chk2, the downstream
      targets of ATR or ATM, were also localized to the centrosomes. Surprisingly, the
      DNA-PK inhibitor vanillin enhanced the level of ATM on centrosomes. Accordingly,
      DNA-PKcs, the catalytic subunit of DNA-PK, was also found on the centrosomes.
      Vanillin altered the phosphorylation of Chk2 in the centrosomes and in whole cell
      extracts. Nucleoplasmic ATM co-immunoprecipitated with Ku70/86, the DNA binding
      subunits of DNA-PK, while vanillin diminished this association. Vanillin did not
      affect microtubule polymerization at the centrosomes but, surprisingly, caused a
      transient enhancement of alpha-tubulin foci in the nucleus. Interestingly, gamma
      tubulin was also present in the nucleus and co-immunoprecipitated with ATR or
      BRCA1. DNA damage led to a reduction of the mentioned checkpoint proteins on the
      centrosomes but increased the level of gamma-tubulin at this organelle. Taken
      together, these results indicate that DNA damage checkpoint proteins may control
      the formation of gamma-tubulin and/or the kinetics of microtubule formation at
      the centrosomes, and thereby couple them to the DNA damage response.

PMID- 17171640
TI  - Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP.
AB  - Androgen-regulated genes (ARG) are implicated in normal and neoplastic growth of
      the prostate. Recently, we reported genomic amplification and/or overexpression
      of a previously known neurotrophic factor, prosaposin, in androgen-independent
      (AI) or metastatic prostate cancer (PCa) cells and tissues. Prosaposin and/or its
      known active molecular derivatives (e.g., saposin C) function as a pluripotent
      growth factor with diverse biological activities that favor malignant phenotypes
      in PCa cells. In addition, prosaposin or saposin C upregulates androgen receptor
      (AR) and AR-target genes (i.e., prostate-specific antigen, Probasin) expression
      and activity in LNCaP cells. Here, we examined prosaposin as an ARG. We report
      that DHT treatment of LNCaP cells increases prosaposin expression. In addition,
      we demonstrate androgen-responsiveness of prosaposin promoter and AR occupancy to
      a hormone-responsive element located in the proximal region of the prosaposin
      promoter. Our data for the first time identify prosaposin as an ARG. This
      observation, together with the pleiotropic growth factor activity of prosaposin,
      might suggest a role for this molecule in AR-dependent progression of prostate
      cancer at its early or late AI-state.

PMID- 17171641
TI  - Functional properties and intracellular signaling of CCN1/Cyr61.
AB  - CCN1/Cyr61 is a member of the protein family that can be promptly induced by
      growth factors. CCN1/Cyr61 promotes cell proliferation, adhesion, and
      differentiation. It plays important roles in angiogenesis and extracellular
      matrix production. In addition, CCN1/Cyr61 has many potential functions in
      tumorigenesis, development, embryo implantation, as well as formation of
      endometriotic lesions. Expression of CCN1/Cyr61 is regulated by a variety of
      agents including cytokines, growth factors, steroid hormones, and some drugs.
      These inducers regulate the transcription of CCN1/Cyr61 through several signaling
      transduction pathways. CCN1/Cyr61 is able to interact either with the cell itself
      or the surrounding cells through an autocrine-paracrine mechanism. It has been
      reported that CCN1/Cyr61 exerts its functions via interacting with at least five
      integrins as well as heparan sulfate proteoglycan. By activating Wnt, NF-kappaB,
      or tyrosine kinase signaling pathways, CCN1/Cyr61 is not only able to control the
      growth of epithelial cells and fibroblasts, but also induce or suppress apoptosis
      in a cell type-specific manner.

PMID- 17171642
TI  - Temporal evolution of gene expression in rat carotid artery following balloon
      angioplasty.
AB  - The success of vascular intervention including angioplasty, stenting, and
      arterial bypass remains limited by negative remodeling resulted in lumen
      restenosis. This study was to characterize the global transcription profile
      reflecting concurrent events along arterial remodeling and neointima formation in
      a rat carotid artery balloon-injury model. Expression profiling of injured and
      control common carotid arteries on days 4, 7, 14 post-injury that mark the major
      pathohistological progression stages of neointimal formation were recorded on
      high-density oligonucleotide arrays. A subset of genes from microarray-based data
      was further studied using quantitative real time RT-PCR and in situ hybridization
      with sequential arterial samples from days 1 to 28 post-injury. The gene-encoded
      proteins were validated with Western blot. Besides temporal induction of a large
      cluster of genes over-represented by cell proliferation and macromolecule
      metabolism gene ontology categories, a fast-evolving inflammation could be
      demonstrated by the induction of Tgfb and other anti-inflammatory genes (e.g.,
      C1qtnf3 (C1q and tumor necrosis factor related protein 3 (predicted))) and a
      shift from type 1 to 2 helper T cell response. The most significant signature of
      the induced neointimal profile is enrichment of genes functionally related to
      angiogenesis and extracellular matrix (ECM) remodeling (e.g., Spp1 (secreted
      phosphoprotein 1), CD44 (CD44 antigen), and Cxcl12 (chemokine (C-X-C motif)
      ligand 12 (stromal cell-derived factor 1)). Some of the genes represent stress
      responsive mesenchymal stromal cell cytokines. This study highlighted mesenchymal
      stromal cell cytokines-driven inflammatory extracellular matrix remodeling, as
      target processes for potential clinical therapeutic intervention.

PMID- 17171643
TI  - Tumor microenvironment abnormalities: causes, consequences, and strategies to
      normalize.
AB  - A solid tumor is an organ-like entity comprised of neoplastic cells and non
      transformed host stromal cells embedded in an extracellular matrix. The
      expression of various genes is influenced by interactions among these cells,
      surrounding matrix, and their local physical and biochemical microenvironment.
      The products encoded by these genes, in turn, control the pathophysiological
      characteristics of the tumor, and give rise to the abnormal organization,
      structure, and function of tumor blood vessels. These abnormalities contribute to
      heterogeneous blood flow, vascular permeability, and microenvironment.
      Proliferating tumor cells produce solid stress which compresses blood and
      lymphatic vessels. As a result of vessel leakiness and lack of functional
      lymphatics, interstitial fluid pressure is significantly elevated in solid
      tumors. Each of these abnormalities forms a physiological barrier to the delivery
      of therapeutic agents to tumors. Furthermore, the metabolic microenvironment in
      tumors such as hypoxia and acidosis hinder the efficacy of anti-tumor treatments
      such as radiation therapy and chemotherapy. A judicious application of anti
      angiogenic therapy has the potential to overcome these problems by normalizing
      the tumor vessels and making them more efficient for delivery of oxygen and
      drugs. Combined anti-angiogenic and conventional therapies have shown promise in
      the clinic.

PMID- 17171644
TI  - Molecular analysis of RANKL-independent cell fusion of osteoclast-like cells
      induced by TNF-alpha, lipopolysaccharide, or peptidoglycan.
AB  - Focusing on the final step of osteoclastogenesis, we studied cell fusion from
      tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells into
      multinuclear cells. TRAP-positive mononuclear cells before generation of
      multinuclear cells by cell fusion were differentiated from RAW264.7 cells by
      treatment with receptor activator of nuclear factor kappa B ligand (RANKL), and
      then the cells were treated with lipopolysaccharide (LPS), followed by culturing
      for further 12 h. LPS-induced cell fusion even in the absence of RANKL.
      Similarly, tumor necrosis factor (TNF)-alpha and peptidoglycan (PGN) induced cell
      fusion, but M-CSF did not. The cell fusion induced by RANKL, TNF-alpha, and LPS
      was specifically blocked by osteoprotegerin (OPG), anti-TNF-alpha antibody, and
      polymyxin B, respectively. LPS- and PGN-induced cell fusion was partly inhibited
      by anti-TNF-alpha antibody but not by OPG. When TRAP-positive mononuclear cells
      fused to yield multinuclear cells, phosphorylation of Akt, Src, extracellular
      signal-regulated kinase (ERK), p38MAPK (p38), and c-Jun NH2-terminal kinase (JNK)
      was observed. The specific chemical inhibitors LY294002 (PI3K), PP2 (Src), U0126
      (MAPK-ERK kinase (MEK)/ERK), and SP600125 (JNK) effectively suppressed cell
      fusion, although SB203580 (p38) did not. mRNA of nuclear factor of activated T
      cells c1 (NFATc1) and dendritic cell-specific transmembrane protein (DC-STAMP)
      during the cell fusion was quantified, however, there was no obvious difference
      among the TRAP-positive mononuclear cells treated with or without M-CSF, RANKL,
      TNF-alpha, LPS, or PGN. Collectively, RANKL, TNF-alpha, LPS, and PGN induced cell
      fusion of osteoclasts through their own receptors. Subsequent activation of
      signaling pathways involving PI3K, Src, ERK, and JNK molecules was required for
      the cell fusion. Although DC-STAMP is considered to be a requisite for cell
      fusion of osteoclasts, cell fusion-inducing factors other than DC-STAMP might be
      necessary for the cell fusion.

PMID- 17171645
TI  - Identification of FAZF as a novel BMP2-induced transcription factor during
      osteoblastic differentiation.
AB  - Bone morphogenetic protein 2 (BMP2) is a key factor in the regulation of
      osteoblastic differentiation; however, its downstream mediators are not fully
      understood. Previously, we identified and characterized transcription factor
      promyelocytic leukemia zinc finger protein (PLZF), composed of an N-terminal
      BTB/POZ and C-terminal zinc finger motifs, as an upstream factor of CBFA1
      (Runx2/core-binding factor 1). PLZF was induced in an osteoblastic
      differentiation medium, but was not induced by BMP2. Here, we report the
      identification of transcription factor fanconi anemia zinc finger protein (FAZF),
      which is closely related to PLZF. FAZF was induced by BMP2 in human mesenchymal
      stem cells (hMSCs). In addition to the full-length FAZF, we also identified
      alternatively spliced mRNAs in which the C-terminal zinc finger motifs were
      deleted (designated BTB/POZ-only FAZF). Both the full-length and BTB/POZ-only
      FAZF mRNAs were equally expressed in BMP2-treated hMSCs. The full-length FAZF was
      exclusively detected in the nucleus, whereas the BTB/POZ-only FAZF protein was
      localized in the cytoplasm of the transfected cells. The full-length FAZF, but
      not the BTB/POZ-only FAZF, increased the expression of osteoblastic
      differentiation markers, including CBFA1, collagen 1A1, osteocalcin, and alkaline
      phosphatase in C2C12 cells. In conclusion, both FAZF and PLZF differentially
      participate in the regulation of osteoblastic differentiation via the BMP2 and
      CBFA1 signaling pathways, respectively.

PMID- 17171646
TI  - Proliferation of human breast cancer cells and anti-cancer action of doxorubicin
      and vinblastine are independent of PKC-alpha.
AB  - Protein kinase C (PKC) has been considered for a potential target of anticancer
      chemotherapy. PKC-alpha has been associated with growth and metastasis of some
      cancer cells. However, the role of PKC-alpha in human breast cancer cell
      proliferation and anticancer chemotherapy remains unclear. In this study, we
      examined whether alterations of PKC-alpha by phorbol esters and PKC inhibitors
      could affect proliferation of human breast cancer MCF-7 cells and the cytotoxic
      effect of chemotherapeutic agents. Exposure for 24 h to doxorubicin (DOX) and
      vinblastine (VIN) caused a concentration-dependent reduction in proliferation of
      MCF-7 cells. However, these two anticancer drugs altered cellular morphology and
      growth pattern in distinct manners. Phorbol 12,13-dibutyrate (PDBu, 100 nM),
      which enhanced activities of PKC-alpha, increased cancer cell proliferation and
      attenuated VIN (1 microM)-induced cytotoxicity. These effects were not affected
      in the presence of 10 nM staurosporine. Phorbol myristate acetate (PMA, 100 nM)
      that completely depleted PKC-alpha also enhanced cancer cell proliferation and
      attenuated VIN-induced cytotoxicity. Three potent PKC inhibitors, staurosporine
      (10 nM), chelerythrine (5 microM) and bisindolylmaleimide-I (100 nM), had no
      significant effect on MCF-7 cell proliferation; staurosporine and chelerythrine,
      but not bisindolylmaleimide-I, attenuated VIN-induced cytotoxicity. Moreover,
      neither phorbol esters nor PKC inhibitors had an effect on cytotoxic effects of
      DOX (1 microM) on MCF-7 cell proliferation. Thus, these data suggest that MCF-7
      cell proliferation or the anti-cancer action of DOX and VIN on breast cancer
      cells is independent of PKC-alpha.

PMID- 17171648
TI  - Induction of abnormal nuclear shapes in two distinct modes by overexpression of
      serine/threonine protein phosphatase 5 in Hela cells.
AB  - Okadaic acid-sensitve serine/threonine protein phosphatase 5 (PP5) is expressed
      ubiquitously in various tissues and is considered to participate in many cellular
      processes. PP5 has a catalytic domain in the C-terminal region and three
      tetratricopeptide repeat (TPR) motifs in the N-terminal region, which are
      suspected to function as a protein-protein interaction domain. Physiological
      roles of PP5 are still largely unknown, although several PP5-binding proteins
      were reported and a few in vivo functions of PP5 were suggested. In the present
      study, the effects of expression of the full-length wild-type PP5 fused with EGFP
      (EGFP-PP5(WT)) and its phosphatase-dead mutant EGFP-PP5(H304A) were investigated.
      Transient expression of either EGFP-PP5(WT) or EGFP-PP5(H304A) in HeLa cells
      induced deformed nuclei with a 10-fold frequency compared to that of EGFP.
      Abnormal-shaped nuclei were also substantially increased by induced moderate
      expression of PP5 in tet-on HeLa cells. Many HeLa cells expressing EGFP-PP5(WT)
      possessed multi-nuclei separated from each other by nuclear membrane, while
      expression of EGFP-PP5(H304A) induced deformed nuclei which were multiple-like in
      shape, but not separated completely and were surrounded by one nuclear membrane.
      These results suggest that PP5 plays important roles at the M-phase of the cell
      cycle, especially in separation of chromosomes and formation of nuclear membrane.

PMID- 17171647
TI  - Suppression of growth factor expression and human vascular smooth muscle cell
      growth by small interfering RNA targeting EGR-1.
AB  - Smooth muscle cell (SMC) proliferation and migration are key processes that occur
      in the reparative response to injury after percutaneous coronary intervention and
      in failed bypass grafts for the treatment of atherosclerosis. In the present
      study, we generated novel synthetic small interfering RNA (siRNA) molecules
      targeting the coding region of human early growth response-1 (EGR-1) mRNA that
      attenuate the expression of EGR-1 and that of fibroblast growth factor-2 (FGF-2)
      and granulocyte-colony stimulating factor (G-CSF). These agents suppressed SMC
      proliferation in a dose-dependent and non-toxic manner and blocked SMC regrowth
      from the wound edge following mechanical injury in vitro. In contrast, the
      scrambled counterpart did not inhibit SMC proliferation, EGR-1 protein expression
      or SMC regrowth after injury. These findings demonstrate that EGR-1 siRNA can
      serve as inhibitors of SMC proliferation and wound repair suggesting that these
      agents may potentially be useful in the control of vascular proliferative
      disorders.

PMID- 17171649
TI  - Osteoprotegerin expression in dendritic cells increases with maturation and is NF
      kappaB-dependent.
AB  - Dendritic cells (DC) comprise a unique leukocyte population which controls
      primary immune responses. Recent studies indicate that DC express osteoprotegerin
      (OPG), a secreted tumor necrosis factor receptor homolog, which regulates DC
      survival, monocyte chemotaxis, and B cell development and function by ligating
      TNF family member receptor activator of NF-kappaB ligand (RANKL). The precise
      regulators of OPG expression in DC have not been investigated. In this study, we
      assessed OPG mRNA steady state levels by Northern blot analysis and OPG protein
      secretion by an immunoassay in monocyte-derived DC of different maturation, and
      the effect of different cytokines and hormones on OPG expression. OPG was
      upregulated with maturation of DC, whereas pretreatment of DC with
      1alpha,25(OH)(2) vitamin D(3), tamoxifen, or dexamethasone, agents that inhibit
      differentiation of DC, decreased OPG expression. In vivo, OPG was found to be
      colocalized with mature CD83(+) DC in human tonsils by immunofluorescence
      confocal microscopy analysis. Furthermore, OPG was upregulated by TNF superfamily
      members TNF-alpha, anti-CD40, and RANKL, and by ligands of the Toll-like/IL-1
      receptor family including IL-1beta, double-stranded RNA (poly I:C), or
      lipopolysaccharide (LPS), all of which induce maturation of DC. Gene silencing by
      small interfering RNA (siRNA) directed against transcription factor NF-kappaB
      abrogated the expression of OPG as demonstrated by real-time PCR. In summary, we
      describe that the expression of OPG by DC increases with maturation and is NF
      kappaB-dependent, possibly regulating immune responses in lymphoid tissues.

PMID- 17171651
TI  - Cyclooxygenase-2 polymorphisms in Parkinson's disease.
AB  - Accumulating evidence indicate that cyclooxygenase-2 (COX-2) is of
      pathophysiological importance for the neurodegeneration in Parkinson's disease
      (PD). For example, in a large epidemiological study, use of NSAIDs was associated
      with a lower risk of PD. Genetic variants of the COX-2 gene might therefore
      influence the risk of developing the disease. The genotype distribution of four
      common single nucleotide polymorphisms (SNPs) in the COX-2 gene (rs689466:A496G,
      rs20417:G926C, rs5277:G3050C, rs5275:C8473T) was analyzed in PD patients and
      control subjects in a Swedish population. No differences could be seen between
      the PD-patient and controls regarding the A496G, G926C, and G3050C SNPs, but the
      allele frequency of the C8473T SNP was found to differ when male patients were
      compared to controls (P = 0.007). In females no difference could be seen between
      PD-patients and controls. In conclusion, the results suggest a possible influence
      of the COX-2 C8473T SNP in PD, although it only seems to be of importance in men.

PMID- 17171650
TI  - Dopaminergic polymorphisms in Tourette syndrome: association with the DAT gene
      (SLC6A3).
AB  - Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by
      involuntary motor and phonic tics. The pattern of inheritance and associated
      genetic abnormality has yet to be fully characterized. A dopaminergic abnormality
      in this disorder is supported by response to specific therapies, nuclear imaging,
      and postmortem studies. In this protocol, dopaminergic polymorphisms were
      examined for associations with TS and attention-deficit hyperactivity disorder
      (ADHD). Polymorphisms investigated included the dopamine transporter (DAT1 DdeI
      and DAT1 VNTR), dopamine receptor (D4 Upstream Repeat and D4 VNTR), dopamine
      converting enzyme (dopamine beta-hydroxylase), and the acid phosphatase locus 1
      (ACP1) gene. DNA was obtained from 266 TS individuals +/- ADHD and 236 controls
      that were ethnicity-matched. A significant association, using a genotype-based
      association analysis, was identified for the TS-total and TS-only versus control
      groups for the DAT1 DdeI polymorphism (AG vs. AA, P = 0.004 and P = 0.01,
      respectively). Population structure, estimated by the genotyping of 27
      informative SNP markers, identified 3 subgroups. A statistical re-evaluation of
      the DAT1 DdeI polymorphism following population stratification confirmed the
      association for the TS-total and TS-only groups, but the degree of significance
      was reduced (P = 0.017 and P = 0.016, respectively). This study has identified a
      significant association between the presence of TS and a DAT polymorphism. Since
      abnormalities of the dopamine transporter have been hypothesized in the
      pathophysiology of TS, it is possible that this could be a functional allele
      associated with clinical expression.

PMID- 17171652
TI  - HOXA1 gene variants influence head growth rates in humans.
AB  - We previously described a significant association between the HOXA1 G218 allele
      and increased head circumference in autism [Conciatori et al. (2004); Biol
      Psychiatry 55:413-419]. The present study reveals identical effects also in
      normal children. HOXA1 A218G alleles and sex explain as much as 10.9 and 6.8% of
      the variance in head circumference in 142 pediatric controls and in 191 autistic
      children, aged 3-16 years (F = 6.777, 3 and 141 df, P < 0.001 and F = 5.588, 3
      and 190 df, P < 0.01, respectively). Instead, no association is found in 183
      adult controls and in 35 pediatric fragile-X patients. Therefore HOXA1 A218G
      alleles significantly influence head growth rates, but not final head size, in
      normal human development. This influence does not differ between normal and
      autistic children, whereas the lack of FMRP seemingly overwhelms HOXA1 effects in
      fragile-X patients.

PMID- 17171653
TI  - Oligodendroglial transcription factor (OLIG1 and OLIG2) mutations are not
      associated with Pelizaeus-Merzbacher-like leukodystrophy.
AB  - The human phenotype with primarily impaired myelination is represented by
      hypomyelinating leukodystrophies. The most frequent form is Pelizaeus-Merzbacher
      disease, which is due to alterations in the PLP1 gene encoding the major myelin
      protein. Another form, Pelizaeus-Merzbacher-like disease, is partly associated
      with mutations in the GJA12 gene encoding gap junction protein alpha 12, but
      seems to be heterogeneous. Olig1 and Olig2 are transcription factors in
      oligodendrocyte development. We postulated that disturbed oligodendroglial
      maturation could be associated with primary hypomyelination in humans and
      analyzed the coding sequence of OLIG1 and OLIG2 in 13 patients from 12 unrelated
      families which were thoroughly characterized with regard to phenotype and
      magnetic resonance imaging results. From our findings we conclude that mutations
      in OLIG1 and OLIG2 are not likely to be associated with this subgroup of
      hypomyelinating disorders.

PMID- 17171654
TI  - The CAPTURE registry: results of carotid stenting with embolic protection in the
      post approval setting.
AB  - BACKGROUND: Pivotal study data examining carotid stenting with embolic protection
      as a less invasive alternative to endarterectomy for high surgical risk patients
      have been acquired under controlled conditions with highly selected physicians
      and hospitals. This report examines outcomes of carotid stenting post-approval
      after diffusion of this technology to a broader cross-section of physicians and
      hospitals. METHODS: The Carotid Acculink/Accunet Post-Approval Trial to Uncover
      Unanticipated or Rare Events (CAPTURE) is a prospective, multi-center registry to
      assess two important aspects of the post-IDE experience: the safety of carotid
      stenting by physicians with varying levels of experience as a measure of the
      adequacy of physician training, and the identification of rare/unexpected device
      related complications. The primary endpoint was a composite of death, any stroke,
      or myocardial infarction within 30 days post-procedure. RESULTS: 3,500 patients
      were enrolled by 353 physicians at 144 sites. The 30-day primary endpoint event
      rate was 6.3% (95% CI: 5.5-7.1%) and did not differ among the three operator
      experience levels (5.3%, 6.0%, and 7.4%; P = 0.31) from most to least
      experienced, respectively. There were no differences in outcomes among physician
      specialties when adjusted for case mix. There were no unanticipated device
      related adverse events. CONCLUSIONS: The results of the CAPTURE study compare
      favorably to those achieved in the predicate pivotal investigations, and suggest
      that the post-approval transfer of this new therapy to the community practice
      setting via carotid stent training programs is effective in preparing physicians
      with varying experience levels and specialty training backgrounds.

PMID- 17171655
TI  - Ultrasound velocity criteria for carotid in-stent restenosis.
AB  - OBJECTIVE: To examine duplex ultrasound (US) criteria for carotid in-stent
      restenosis (ISR). BACKGROUND: Carotid artery stent (CAS) placement is an
      alternative to surgery for the treatment of carotid stenosis in high surgical
      risk patients. US is the primary method used to follow carotid stent patency.
      This study investigates US velocity measurements in carotid ISR. METHODS: Two
      hundred sixty consecutive patients with CAS placement from June 2000 to June 2004
      were followed with serial US. ISR was determined by using the standard US
      velocity criteria for nonstented carotid artery using peak systolic velocity
      (PSV), end-diastolic velocity (EDV), and internal carotid artery to common
      carotid velocity ratio (ICA/CCA ratio). Patients suspected of having carotid ISR
      > or =50% by US, underwent invasive angiography with stenosis graded by NASCET
      criteria. Results were compared to patients with nonstented carotid artery
      stenosis using Two-tailed Student's t-test. RESULTS: PSV and ICA/CCA ratio
      increased to a greater degree in ISR. In 50-69% stenotic arteries, the mean
      ICA/CCA ratio was 2.76 +/- 0.7 in the ISR group compared to 2.04 +/- 0.3 in the
      nonstented carotid group (P < 0.05). In > or =70% stenotic arteries, there were
      increases in PSV (520 +/- 93 vs. 362 +/- 60, P < 0.05) and ICA/CCA ratio (7.58 +/
      2 vs. 4.51 +/- 1.3, P < 0.05) in ISR versus nonstented carotid arteries,
      respectively. CONCLUSION: PSV and ICA/CCA ratio in ISR increased to a greater
      extent for angiographic stenosis > or =50%. PSV 240 cm/sec and ICA/CCA ratio 2.45
      are optimal thresholds for > or =50% ISR, and PSV 450 cm/sec and ICA/CCA ratio
      4.3 are optimal thresholds for > or =70% ISR.

PMID- 17171656
TI  - No significant association between response to methylphenidate and genes of the
      dopaminergic and serotonergic systems in a sample of Brazilian children with
      attention-deficit/hyperactivity disorder.
AB  - Few studies on pharmacogenetics of Attention-Deficit/Hyperactivity Disorder
      (ADHD) have been conducted. Most of them evaluated dopaminergic genes resulting
      in positive and negative findings. We assessed effects of polymorphisms in
      candidate dopaminergic (DRD4, DAT1) and serotonergic genes (HTR1B, HTR2A, and 5
      HTT) on the response to treatment in 111 patients for whom methylphenidate (MPH)
      was prescribed. Outcome measures (Swanson, Nolan, and Pelham scale-version IV,
      Children Global Assessment Scale, Barkley's Stimulants Side Effects Rating Scale)
      were assessed at baseline and 1 month after the intervention. No significant
      association was detected between polymorphisms assessed and both response and
      side effects to MPH. Prospective multi-site controlled studies with larger sample
      sizes are needed in order to disentangle the role of candidate genes in response
      to ADHD treatment.

PMID- 17171657
TI  - Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children
      with attention-deficit/hyperactivity disorder (ADHD): an update.
AB  - Polymorphisms of the dopamine receptor D4 gene DRD4, 11p15.5, have previously
      been associated with attention-deficit/hyperactivity disorder (ADHD) [Bobb et
      al., 2005; Am J Med Genet B Neuropsychiatr Genet 132:109-125; Faraone et al.,
      2005; Biol Psychiatry 57:1313-1323; Thapar et al., 2005; Hum Mol Genet 14 Spec
      No. 2:R275-R282]. As a follow up to a pilot study [see Castellanos et al., 1998;
      Mol Psychiatry 3:431-434] consisting of 41 probands and 56 controls which found
      no significant association between the DRD4 7-repeat allele in exon 3 and ADHD, a
      greatly expanded study sample (cases n = 166 and controls n = 282) and long term
      follow-up (n = 107, baseline mean age n = 9, follow-up mean age of n = 15)
      prompted reexamination of this gene. The DRD4 7-repeat allele was significantly
      more frequent in ADHD cases than controls (OR = 1.2; P = 0.028). Further, within
      the ADHD group, the 7-repeat allele was associated with better cognitive
      performance (measured by the WISC-III) (P = 0.013-0.07) as well as a trend for
      association with better long-term outcome. This provides further evidence of the
      role of the DRD4 7-repeat allele in the etiology of ADHD and suggests that this
      allele may be associated with a more benign form of the disorder.

PMID- 17171658
TI  - Association between the 120-bp duplication of the dopamine D4 receptor gene and
      attention deficit hyperactivity disorder: genetic and molecular analyses.
AB  - Abnormalities of the dopamine neurotransmission have been hypothesized to play an
      important role in the pathophysiology of attention deficit hyperactivity disorder
      (ADHD). Promoter variants of the dopamine D4 receptor gene (DRD4) have attracted
      particular interest due to their possible role in regulation of gene
      transcription. Here we describe the haplotype analysis of the 120 base pair
      duplication (120-bp dup) and three SNPs (-616C/G, -615A/G, -521C/T) in the 5'
      region of the DRD4 gene among children with ADHD. We observed a trend (chi(2) =
      14.905, df = 9, P = 0.093) in the four-locus haplotype distribution between ADHD
      probands (N = 173) and controls (N = 284). The homozygote genotype of the 1
      repeat form of the 120-bp dup (1-1) had a significantly higher frequency among
      ADHD children than in controls (8.1% vs. 3.2%, chi(2) = 5.526, df = 1, P = 0.019,
      Odds Ratio = 2.71). In addition, a novel, 4-repeat allele was identified among
      ADHD patients. This particular allele has been cloned to the luciferase
      expression vector and its transcriptional activity has been compared to the 1-
      and 2-repeat allele. The number of repeats of the 120-bp dup was found to have an
      effect on transcriptional activity in both neuroblastoma and retinoblastoma cell
      lines in a dose-dependent manner (1-repeat > 2-repeat > 4-repeat). These results
      suggest that the 1-repeat form of the 120-bp dup might be a risk factor of ADHD,
      especially in the homozygous form and/or in the context of certain haplotypes.

PMID- 17171659
TI  - Sequence variants within exon 1 of MECP2 occur in females with mental
      retardation.
AB  - A new splice variant of the Rett syndrome gene, MECP2, was recently identified,
      that includes coding sequence from exon 1, and is the predominant transcript in
      the central nervous system. This sequence encodes polyalanine and polyglycine
      stretches within the N-terminal portion of MeCP2, and may confer novel functional
      properties to the protein. We screened autism, mental retardation (MR), and
      control populations for sequence variation within this region, and identified
      variation in approximately 1% of MR cases screened (N = 1,410). No variants were
      identified in the autism sample (N = 401). Most of these variants occur within a
      trinucleotide repeat region and result in change in number of alanine or glycine
      residues within the repeat stretches. We suggest some of these variants may be a
      relatively frequent cause of non-specific MR or developmental delay.

PMID- 17171660
TI  - Covalent immobilization of redox enzyme on electrospun nonwoven
      poly(acrylonitrile-co-acrylic acid) nanofiber mesh filled with carbon nanotubes:
      a comprehensive study.
AB  - In this work, novel conductive composite nanofiber mesh possessing reactive
      groups was electrospun from solutions containing poly(acrylonitrile-co-acrylic
      acid) (PANCAA) and multi-walled carbon nanotubes (MWCNTs) for redoxase
      immobilization, assuming that the incorporated MWCNTs could behave as electrons
      transferor during enzyme catalysis. The covalent immobilization of catalase from
      bovine liver on the neat PANCAA nanofiber mesh or the composite one was processed
      in the presence of EDC/NHS. Results indicated that both the amount and activity
      retention of bound catalase on the composite nanofiber mesh were higher than
      those on the neat PANCAA nanofiber mesh, and the activity increased up to 42%.
      Kinetic parameters, K(m) and V(max), for the catalases immobilized on the
      composite nanofiber mesh were lower and higher than those on the neat one,
      respectively. This enhanced activity might be ascribed to either promoted
      electron transfer through charge-transfer complexes and the pi system of carbon
      nanotubes or rendered biocompatibility by modified MWCNTs. Furthermore, the
      immobilized catalases revealed much more stability after MWCNTs were incorporated
      into the polymer nanofiber mesh. However, there was no significant difference in
      optimum pH value and temperature, thermal stability and operational stability
      between these two immobilized preparations, while the two ones appeared more
      advantageous than the free in these properties. The effect of MWCNTs
      incorporation on another redox enzyme, peroxidase, was also studied and it was
      found that the activity increased by 68% in comparison of composite one with neat
      preparation.

PMID- 17171661
TI  - Association analysis of the protein phosphatase 1 regulatory subunit 1B (PPP1R1B)
      gene with nicotine dependence in European- and African-American smokers.
AB  - The protein phosphatase 1 regulatory subunit 1B gene (PPP1R1B; also known as
      dopamine and cAMP-regulated phosphoprotein; DARPP32) is a target for the actions
      of dopamine. Because the mesolimbic dopaminergic system is implicated in the
      reinforcing effects of many drugs, including nicotine, PPP1R1B is considered a
      plausible candidate for involvement in the development of vulnerability to
      nicotine dependence (ND). Further, this gene is located within a region on
      chromosome 17 that demonstrated "suggestive linkage" to ND in our previous genome
      wide scan. In the present study, we analyzed six single nucleotide polymorphisms
      (SNPs) within PPP1R1B for association with three ND measures: smoking quantity
      (SQ), the heaviness of smoking index (HSI), and the Fagerstrom Test for ND (FTND)
      score. Our sample consisted of 602 nuclear families of African-American (AA) or
      European-American (EA) origin. No significant associations were found for single
      SNPs after correction for multiple testing. However, haplotype analysis indicated
      that in the EA sample, the C-T-G-C haplotype formed by rs2271309-rs907094
      rs3764352-rs3817160 with a frequency of 32.0% was significantly associated with
      SQ (Z = 2.50; P = 0.01), even after Bonferroni correction. No significant
      associations with haplotypes were found in the AA sample. In summary, our
      findings provide the first evidence for the potential involvement of PPP1R1B in
      the etiology of ND and further investigation is thus warranted.

PMID- 17171662
TI  - No association between the Ser9Gly polymorphism of the dopamine D3 receptor gene
      and schizophrenia in a Spanish sample.
AB  - This study aims to further evaluate the controversial association between the
      Ser9Gly polymorphism in codon 9 of the D3 dopamine receptor gene (DRD3) and
      schizophrenia in psychiatric inpatients acutely hospitalized in two general
      hospitals in Madrid, Spain. The Ser9Gly polymorphism of the DRD3 was examined in
      178 schizophrenic patients, 286 patients with other psychiatric diagnoses, and
      132 controls recruited. Genotype frequencies were in Hardy-Weinberg equilibrium.
      No association was found between schizophrenia and the Ser9Gly polymorphism of
      the D3 dopamine receptor gene.

PMID- 17171663
TI  - Preliminary evidence for linkage to chromosome 1q31-32, 10q23.3, and 16p13.3 in a
      South African cohort with bipolar disorder.
AB  - Although the genetic variants predisposing to the development of bipolar disorder
      (BPD) have yet to be conclusively identified, replicated reports of linkage to
      particular chromosomal regions have been encouraging. Here we carried out a non
      parametric linkage analysis of nine of these candidate loci in a unique South
      African sample of 47 BPD pedigrees (N = 350). Three polymorphic markers per
      region of interest (3 x 9) were typed in a Caucasian cohort of Afrikaner and
      British origin. Statistically significant evidence for linkage was obtained at
      1q31-32, 10q23.3, and 16p13.3 with maximum NPL scores of 2.52, 2.01, and 1.84,
      respectively. Our results add to the growing evidence that these chromosomal
      regions harbor genetic variants that play a role in the development of bipolar
      spectrum illness. Negative results were obtained for the remaining six candidate
      loci, possibly due to limited statistical power.

PMID- 17171664
TI  - Linkage of schizophrenia with chromosome 1q32 in Korean multiplex families.
AB  - Chromosome 1q contains a few loci for which modest evidence of linkage with
      schizophrenia has been reported in several independent studies. However, markers
      showing the peak linkage signal are dispersed over a large chromosomal region. In
      addition, inconsistent findings have been generated from different populations or
      different subgroups of the same populations. The purpose of the current study is
      to determine whether those loci are linked to schizophrenia in the Korean
      population. We investigated 46 Korean multiplex schizophrenia families, initially
      using 11 microsatellite markers spanning around 91 cM region of 1p22
      approximately 42. In a non-parametric linkage analysis, D1S249 located on 1q32.1
      showed statistical evidence suggestive of linkage. At the second stage analysis
      for narrowing down the region, four additional nearby markers were genotyped. In
      the single point analysis, we found another suggestive linkage signal at D1S2891.
      The highest NPL score of 2.67 (P = 0.0039) was obtained in the multi-point
      analysis. This study provides supportive evidence for linkage of chromosome 1q32
      with schizophrenia.

PMID- 17171665
TI  - Evaluation of association of SNPs in the TNF alpha gene region with
      schizophrenia.
AB  - The association of the tumor necrosis factor alpha (TNFalpha) -G308A promoter
      polymorphism with schizophrenia has complemented clinical findings of increased
      levels of the TNFalpha cytokine in schizophrenic patients, with some support for
      a functional consequence of the variant. Our previous studies of genetic causes
      in schizophrenia supported findings of linkage to the major histocompatibility
      complex (MHC) region where the TNFalpha gene is located as well as association
      with the -G308A promoter polymorphism. While the common G-allele shows
      association in our sample, association with the A-allele has been reported by
      other groups. This suggests linkage disequilibrium (LD) rather than direct
      involvement in the disorder. In order to define LD of DNA variants with the
      disorder in this area, we analyzed 36 SNPs in a 165-kb region around this
      polymorphism. We detected nominally significant associations (P < 0.05) of three
      markers (including the -G308A promoter polymorphism) and multiple haplotypes with
      schizophrenia in our sample of 204 families (79 sib-pairs and 125 trios). The
      association is largely restricted to a 30 kb high LD region/block and should
      assist in the identification of a schizophrenia susceptibility gene within the
      block or elsewhere in the MHC.

PMID- 17171668
TI  - Early evolution and biogeography of lorisiform strepsirrhines.
AB  - This brief review summarizes new paleontological and molecular data that together
      support a late middle Eocene Afro-Arabian origin for crown Lorisiformes.
      Phylogenetic analysis indicates that late Eocene Karanisia is a possible stem
      lorisiform, late Eocene Saharagalago and Wadilemur and Miocene Komba are stem
      galagids, and early Miocene Mioeuoticus and Progalago may be crown lorisids.
      Character evolution along the lorisid and galagid stem lineages is reconstructed
      as having occurred primarily in postcranial and dental morphology, respectively.
      These patterns have important implications for interpreting an early lorisiform
      fossil record that is still composed primarily of jaws and isolated teeth.

PMID- 17171669
TI  - Interspecific analysis of covariance structure in the masticatory apparatus of
      galagos.
AB  - The primate masticatory apparatus (MA) is a functionally integrated set of
      features, each of which performs important functions in biting, ingestive, and
      chewing behaviors. A comparison of morphological covariance structure among
      species for these MA features will help us to further understand the evolutionary
      history of this region. In this exploratory analysis, the covariance structure of
      the MA is compared across seven galago species to investigate 1) whether there
      are differences in covariance structure in this region, and 2) if so, how has
      this covariation changed with respect to size, MA form, diet, and/or phylogeny?
      Ten measurements of the MA functionally related to bite force production and load
      resistance were obtained from 218 adults of seven galago species. Correlation
      matrices were generated for these 10 dimensions and compared among species via
      matrix correlations and Mantel tests. Subsequently, pairwise covariance disparity
      in the MA was estimated as a measure of difference in covariance structure
      between species. Covariance disparity estimates were correlated with pairwise
      distances related to differences in body size, MA size and shape, genetic
      distance (based on cytochrome-b sequences) and percentage of dietary foods to
      determine whether one or more of these factors is linked to differences in
      covariance structure. Galagos differ in MA covariance structure. Body size
      appears to be a major factor correlated with differences in covariance structure
      among galagos. The largest galago species, Otolemur crassicaudatus, exhibits
      large differences in body mass and covariance structure relative to other
      galagos, and thus plays a primary role in creating this association. MA size and
      shape do not correlate with covariance structure when body mass is held constant.
      Diet also shows no association. Genetic distance is significantly negatively
      correlated with covariance disparity when body mass is held constant, but this
      correlation appears to be a function of the small body size and large genetic
      distance for Galagoides demidoff. These exploratory results indicate that
      changing body size may have been a key factor in the evolution of the galago MA.

PMID- 17171670
TI  - Perinatal size and maturation of the olfactory and vomeronasal neuroepithelia in
      lorisoids and lemuroids.
AB  - Explanations for the chemosensory abilities of newborn mammals focus primarily on
      food (milk) acquisition and communication (e.g., maternal-infant bonding).
      However, the relative importance of the main and accessory (vomeronasal)
      olfactory systems is hypothesized to differ at birth between altricial and
      precocial mammals. Strepsirrhines (lemurs and lorises) possess main and accessory
      olfactory systems, and vary in life-history traits related to infant dependency
      and maturation. Accordingly, this study examines the size and maturational
      characteristics of vomeronasal (VNNE) and olfactory (OE) neuroepithelia in
      strepsirrhines. Serially sectioned heads of 18 infant cadavers were examined
      microscopically for neuroepithelial distribution. Measurements were taken on the
      length of the nasal fossa on one side that was occupied by VNNE and OE. The data
      were corrected for body size using the cranial length or body mass, and were then
      examined for correlation with several life-history variables, as well as activity
      pattern. In addition, immunohistochemistry was used to identify cells in the VNNE
      and OE that express olfactory marker protein (OMP), a marker of mature olfactory
      neurons. Relative OE extent was not significantly correlated with any of the life
      history variables. Relative VNNE length was negatively correlated with relative
      gestation length and relative neonatal mass (P<0.05). However, when we corrected
      for phylogenetic relationships, we found no significant correlations between
      either of the neuroepithelial measurements and life-history variables.
      Immunohistochemical findings suggest that OE has more OMP-reactive cells than
      VNNE in all species. OMP-reactive cells appear to be less numerous in diurnal
      species compared to most nocturnal species. These results indicate that the VNNE
      may be relatively longer at birth in altricial species. However, it remains
      uncertain how phylogeny and/or ontogeny may explain these findings.

PMID- 17171671
TI  - Not all lorises are slow: rapid arboreal locomotion in Loris tardigradus of
      southwestern Sri Lanka.
AB  - The unique slow-climbing quadrupedalism of Asian lorises has been the subject of
      numerous studies; however, qualitative observations of more rapid locomotion have
      occasionally been reported. Field studies of the red slender loris have revealed
      the habitual use of unexpectedly high-speed locomotion by the so-called "sloth of
      the primate world." Novel video footage permitted the first quantitative
      kinematic analysis of rapid quadrupedalism in wild lorises. Observations revealed
      that this previously unexplored behavior is far from infrequent, with 26% of red
      slender loris locomotor activity being dedicated to high-velocity arboreal
      quadrupedalism. This locomotor pattern may represent a primitive retention of the
      rapid, scrambling quadrupedalism that is observed in other strepsirhines, or it
      may constitute a more recent specialization of this smallest loris taxon.

PMID- 17171673
TI  - Cranial ontogeny, diet, and ecogeographic variation in African lorises.
AB  - A series of 22 craniodental measurements were obtained for the three subspecies
      of potto (Perodicticus) and angwantibos (Arctocebus). To describe patterns of
      variation in Perodicticus, a discriminant function analysis (DFA) was performed
      with adult data. To investigate the ecogeographic correlates of size variation in
      Perodicticus, adult cranial dimensions were compared with field data on
      latitudinal and longitudinal coordinates for available specimens as well as
      altitudinal data for a more limited sample. Ontogenetic series for larger-bodied
      Perodicticus and smaller-bodied Arctocebus were compared to test the hypothesis
      that inter- and intrageneric variation in skull form results from the
      differential extension/truncation of shared patterns of relative growth, and to
      assess morphological variation in the masticatory complex of sister taxa with
      differing dietary habits. Analyses of relative growth indicate that skull
      proportions in Perodicticus subspecies are largely ontogenetically scaled. In
      comparisons between Perodicticus and Arctocebus, most facial dimensions also are
      ontogenetically scaled, with all but one of the seven divergent comparisons
      (interorbital breadth) representing a feature of the masticatory apparatus. The
      DFA provided independent support for prior classifications of Perodicticus into
      three taxa. Size differentiation in African lorises appears to be correlated with
      altitudinal variation (Bergmann's Rule) as well as character displacement. The
      smallest pottos, P. p. potto, occupy low-lying coastal habitats in western
      Africa, whereas the larger, eastern forms inhabit higher, presumably colder
      elevations. The largest potto, P. p. edwardsi, is sympatric throughout most of
      its range with the smallest and most insectivorous African lorises (Arctocebus).
      A basis for intrageneric taxonomic variation in Perodicticus is supported by such
      nonclinal size variation, as well as divergences in the ontogeny of masticatory
      proportions corresponding to interspecific variation in dietary proclivities.

PMID- 17171674
TI  - Morphological and functional differentiation in the lumbar spine of lorisids and
      galagids.
AB  - The striking contrast in positional behavior exhibited by lorisids (slow
      quadrupedalism/suspension) and galagids (leaping/quadrupedalism) is well
      reflected in their postcranial morphology, particularly in the limbs. Although
      they exhibit very different spinal postures and movements, vertebral adaptations
      have been less well explored in these taxa. This study addressed morphological
      and functional differentiation in the lumbar vertebrae of four species of
      lorisids and five species of galagids. Linear and angular measurements of lumbar
      vertebrae were compared among taxa using canonical variates analysis (CVA) in
      conjunction with pairwise comparisons among selected variables. The results were
      interpreted in the context of a broader comparative sample, including the
      addition of indriids to the CVA. Compared to galagids, lorisids have relatively
      shorter lumbar spinous processes that are more perpendicularly (to caudally)
      oriented relative to a coronal plane. Lorisids also have relatively wider laminae
      and more transversely oriented prezygapophyses. These features promote lumbar
      stability and reflect antipronogrady, multiplane spinal movements, and upside
      down suspension. Within lorisids, vertebral body length and height vary with body
      size, reflecting the additional resistance to bending that is required for larger
      body sizes. Galagid lumbar shape is influenced by body size, but does not show
      strong variation in accordance with positional behavior differences as defined
      here. Galagids, indriids, and lorisids are distinct in lumbar morphology and
      function, but their similarities in lumbar length reduction are suggestive of
      antipronograde postures in the common ancestor of the galagids, including those
      who have shifted to a more quadrupedal locomotor repertoire.

PMID- 17171675
TI  - Limb growth in captive Galago senegalensis: getting in shape to be an adult.
AB  - Since primate infants are not simply miniature adults, adult shape results from
      differential growth patterns of individual body segments. Initially an infant
      relies on its mother for transportation, and later begins independent locomotion.
      Skeletal growth patterns must meet the functional demands of independent
      locomotion. In this study we sought to determine whether Galago senegalensis
      braccatus follow the general primate pattern of decreasing intermembral index
      (IMI) throughout ontogeny. We also asked whether ontogenetic attainment of adult
      limb proportions coincides with attainment of independent locomotion, i.e., do
      infants reach adult limb proportions near the time they begin independent
      locomotion (approximately 7 weeks of age)? Mixed-longitudinal data were taken
      from a sample of 10 captive-born Galago senegalensis. Linear lengths of the
      trunk, arm, forearm, thigh, and leg were measured in the animals from birth until
      they were approximately 500 days old. The IMI and the ratio of each limb segment
      to both trunk length and the cube root of body mass were calculated. The results
      of a Mann-Whitney Wilcoxon rank-sum test for unmatched samples indicate that G.
      senegalensis do exhibit the primate pattern of decreasing IMI throughout
      ontogeny, and that the IMIs of infants at the time of initial locomotor
      independence are significantly higher than those of adult IMIs. Some (but not
      all) measures of relative limb lengths differed between neonates or 7-week-old
      infants and adults. Therefore, the hypothesis that infants acquire adult limb
      proportions by the time they begin independent locomotion is not supported by
      this study. The current results indicate that ontogenetic shape changes in
      galagos are a complex process and apparently cannot be explained by simple
      initial locomotor competency.

PMID- 17171677
TI  - Phylogenetic relationships among the Lorisoidea as indicated by craniodental
      morphology and mitochondrial sequence data.
AB  - The phylogeny of the Afro-Asian Lorisoidea is controversial. While postcranial
      data attest strongly to the monophyly of the Lorisidae, most molecular analyses
      portray them as paraphyletic and group the Galagidae alternately with the Asian
      or African lorisids. One of the problems that has bedevilled phylogenetic
      analysis of the group in the past is the limited number of taxa sampled for both
      ingroup families. We present the results of a series of phylogenetic analyses
      based on 635 base pairs (bp) from two mitochondrial genes (12S and 16S rRNA) with
      and without 36 craniodental characters, for 11 galagid and five lorisid taxa. The
      outgroup was the gray mouse lemur (Microcebus murinus). Analyses of the molecular
      data included maximum parsimony (MP), neighbor joining (NJ), maximum likelihood
      (ML), and Bayesian methods. The model-based analyses and the combined
      "molecules+morphology" analyses supported monophyly of the Lorisidae and
      Galagidae. The lorisids form two geographically defined clades. We find no
      support for the taxonomy of Galagidae as proposed recently by Groves [Primate
      Taxonomy, Washington, DC: Smithsonian Institution Press. 350 p, 2001]. The
      taxonomy of Nash et al. [International Journal of Primatology 10:57-80, 1989] is
      supported by the combined "molecules+morphology" analysis; however, the model
      based analyses suggest that Galagoides may be an assemblage of species united by
      plesiomorphic craniodental characters.

PMID- 17171678
TI  - Comparative penile morphology of East African galagos of the genus Galagoides
      (family Galagidae): implications for taxonomy.
AB  - Recent studies on the comparative penile morphology of galagos have revealed
      complex patterns that vary among both genera and species, and help with species
      identification. So far the penile morphologies of 14 galago species have been
      described and an identification key has been proposed. The present study extends
      and revises previous work. Wild Galagoides cocos, G. granti, G. zanzibaricus and
      G. rondoensis from the Eastern Arc Mountains and coastal forests of Tanzania and
      Kenya were live-trapped, and one species (G. orinus) was examined using a museum
      specimen. Penile morphology was photographed, traced, and described
      qualitatively. All of the mature males had penile spines. Spines were absent or
      indistinct in immature males of all of the species. The penile morphologies of G.
      cocos, G. granti, and G. zanzibaricus are similar in their overall distribution
      and type of spines, but differ in the shape of the glans penis. Both G. orinus
      and G. rondoensis have divergent penile morphologies compared to all other
      galagos, and are probably phylogenetically distinct. The results support other
      recent morphological and behavioral studies that consider these five galagos to
      be distinct species. The evolution of the baculum and spines is thought to be
      linked to sexual selection in multimale mating systems, but the mechanisms
      involved are not entirely understood. Adult male G. rondoensis appear to display
      the penile spines by exposing the distal section of the penis.

PMID- 17171679
TI  - Histomorphology of the mandibular condylar cartilage in greater galagos (Otolemur
      spp.).
AB  - The functional morphology of the primate craniomandibular complex and
      temporomandibular joint (TMJ) components is frequently discussed in terms of
      gross skeletal structure. At the histomorphologic level, however, the TMJ has
      only been studied in Old World anthropoids. The present study is designed to
      describe the microanatomy of the condylar cartilage of the TMJ in two closely
      related species of greater galago: the exudativorous Otolemur crassicaudatus and
      the frugivorous O. garnettii. TMJs with intact joint capsules were harvested from
      adult, cadaveric specimens of these species (four O. crassicaudatus and five O.
      garnettii). The samples were decalcified, processed for paraffin sectioning, and
      sectioned at 10-18 microm in the coronal plane. The samples were then stained
      with hematoxylin/eosin, Gomori trichrome, and Alcian blue, and examined with a
      photomicroscope. Generally, condylar cartilage in O. crassicaudatus was thickest
      both laterally and centrally, while O. garnettii had the relatively thickest
      cartilage laterally. Both species displayed a superficial articular zone, a
      middle proliferative zone, and a deeply located hypertrophic zone in the condylar
      cartilage. O. crassicaudatus typically had the greatest cell density in each of
      these zones. In addition, O. crassicaudatus had focal concentrations of Alcian
      blue laterally and centrally, while O. garnettii had the greatest reactivity in
      the central portion only. These results suggest that O. crassicaudatus may be
      specialized to resist greater compressive force at the TMJ condylar cartilage in
      specific regions of the mandibular condyle.

PMID- 17171680
TI  - Targets of genome copy number reduction in primary breast cancers identified by
      integrative genomics.
AB  - The identification of specific oncogenes and tumor suppressor genes in regions of
      recurrent aneuploidy is a major challenge of molecular cancer research. Using
      both oligonucleotide single-nucleotide polymorphism and mRNA expression arrays,
      we integrated genomic and transcriptional information to identify and prioritize
      candidate cancer genes in regions of increased and decreased chromosomal copy
      number in a cohort of primary breast cancers. Confirming the validity of this
      approach, several regions of previously-known copy number (CN) alterations in
      breast cancer could be successfully reidentified. Focusing on regions of
      decreased CN, we defined a prioritized list of eighteen candidate genes, which
      included ARPIN, FBN1, and LZTS1, previously shown to be associated with cancers
      in breast or other tissue types, and novel genes such as P29, MORF4L1, and
      TBC1D5. One such gene, the RUNX3 transcription factor, was selected for further
      study. We show that RUNX3 is present at reduced CNs in proportion to the rest of
      the tumor genome and that RUNX3 CN reductions can also be observed in a breast
      cancer series from a different center. Using tissue microarrays, we demonstrate
      in an independent cohort of over 120 breast tissues that RUNX3 protein is
      expressed in normal breast epithelium but not fat and stromal tissue, and widely
      down-regulated in the majority of breast cancers (>85%). In vitro, RUNX3
      overexpression suppressed the invasive potential of MDA-MB-231 breast cancer
      cells in a matrigel assay. Our results demonstrate the utility of integrative
      genomic approaches to identify novel potential cancer-related genes in primary
      tumors. This article contains Supplementary Material available at
      http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 17171681
TI  - DNA cleavage and Trp53 differentially affect SINE transcription.
AB  - Among the cellular responses observed following treatment with DNA-damaging
      agents is the activation of Short Interspersed Elements (SINEs; retrotransposable
      genetic elements that comprise over 10% of the human genome). By placing a human
      SINE (the Alu element) into murine cells, we have previously shown that DNA
      damaging agents such as etoposide can induce both upregulation of SINE transcript
      levels and SINE retrotransposition. A similarly cytotoxic (but not genotoxic)
      exposure to vincristine was not associated with SINE activation. Here we
      demonstrate that multiple other genotoxic exposures are associated with
      upregulation of SINE transcript levels. By comparing the effects of similarly
      cytotoxic doses of the topoisomerase II inhibitors etoposide and merbarone, we
      confirm that DNA strand breakage is specifically associated with SINE induction.
      By evaluating transcription rate and RNA stability, we demonstrate that SINE
      induction by genotoxic exposure is associated with transcriptional induction and
      not with transcript stabilization. Finally we demonstrate that SINE induction by
      genotoxic stress is mediated by a Trp53-independent pathway, and in fact that
      Trp53 plays an inhibitory role in attenuating the transcriptional induction of
      SINE elements following exposure to a genotoxic agent. Together these data
      support a model in which initial DNA damage can trigger genomic instability due
      to SINE activation, a response which may be amplified in cancer cells lacking
      functional TP53.

PMID- 17171682
TI  - Molecular characterization of human multiple myeloma cell lines by integrative
      genomics: insights into the biology of the disease.
AB  - To investigate the patterns of genetic lesions in a panel of 23 human multiple
      myeloma cell lines (HMCLs), we made a genomic integrative analysis involving
      FISH, and both gene expression and genome-wide profiling approaches. The
      expression profiles of the genes targeted by the main IGH translocations showed
      that the WHSC1/MMSET gene involved in t(4;14)(p16;q32) was expressed at different
      levels in all of the HMCLs, and that the expression of the MAF gene was not
      restricted to the HMCLs carrying t(14;16)(q32;q23). Supervised analyses
      identified a limited number of genes specifically associated with t(4;14) and
      involved in different biological processes. The signature related to MAF/MAFB
      expression included the known MAF target genes CCND2 and ITGB7, as well as genes
      controlling cell shape and cell adhesion. Genome-wide DNA profiling allowed the
      identification of a gain on chromosome arm 1q in 88% of the analyzed cell lines,
      together with recurrent gains on 8q, 18q, 7q, and 20q; the most frequent
      deletions affected 1p, 13q, 17p, and 14q; and almost all of the cell lines
      presented LOH on chromosome 13. Two hundred and twenty-two genes were found to be
      simultaneously overexpressed and amplified in our panel, including the BCL2 locus
      at 18q21.33. Our data further support the evidence of the genomic complexity of
      multiple myeloma and reinforce the role of an integrated genomic approach in
      improving our understanding of the molecular pathogenesis of the disease. This
      article contains Supplementary Material available at
      http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 17171683
TI  - ISCN (2005) is not acceptable for describing clonal evolution in cancer.

PMID- 17171684
TI  - Common polymorphisms in TP53 and MDM2 and the relationship to TP53 mutations and
      clinical outcomes in women with ovarian and peritoneal carcinomas.
AB  - The importance of somatic TP53 mutations and germline TP53 codon 72 genotype in
      the survival of women with epithelial ovarian cancer is controversial. Recent
      data suggest that a promoter polymorphism in the MDM2 gene may influence age of
      cancer onset in a gender-specific fashion. We sought to determine the
      relationship between somatic TP53 mutations, germline genotypes at TP53 codon 72
      and MDM2 SNP309, and overall survival and response to chemotherapy in a large
      series of patients with ovarian and peritoneal carcinomas. Of the 188 cancers,
      103 (54.8%) had a TP53 mutation, of which 71% were missense mutations and 29%
      were null mutations. TP53 mutation status and mutation type (null vs. missense)
      did not influence response to therapy or overall survival. Women with the codon
      72 Pro/Pro had a decreased overall survival (median, 29 months) compared with
      women with one or two arginine alleles (median, 49 months; P=0.04). Somatic
      mutation or deletion was equally common for either codon 72 allele. Age of
      diagnosis was not influenced by codon 72 but showed a trend for younger age in
      women with somatic TP53 mutations and the MDM2 G/G genotype.

PMID- 17171685
TI  - Genome-wide linkage scan for breast cancer susceptibility loci in Swedish
      hereditary non-BRCA1/2 families: suggestive linkage to 10q23.32-q25.3.
AB  - The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years
      ago and, depending on population, mutations in these genes are responsible for a
      varying percentage of familial breast cancer. In more than half the families, the
      increased risk of breast cancer cannot be explained by mutations in these genes,
      and the goal of this study was to locate novel susceptibility genes. One of the
      main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast
      cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant
      susceptibility genes, along with ethnic and geographic differences. In this
      study, one large family and 13 small to medium-sized families with multiple cases
      of breast cancer were analyzed by genome-wide linkage analysis. The genome scan
      was performed by genotype analysis of 10,000 SNP markers on microarrays. The
      strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region
      10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10
      on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin,
      two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12
      q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32
      q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the
      suggested regions may harbor genes that are involved in the development of breast
      cancer.

PMID- 17171686
TI  - WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors.
AB  - Chromosome rearrangements involving 12q13-15 are frequent among several tumors,
      including pleomorphic adenomas. The common molecular target for these aberrations
      is the HMGA2 gene, but various fusion partners of HMGA2 have been reported in
      tumors. Here we report the identification of the WNT inhibitory factor 1 (WIF1)
      gene as a novel HMGA2 fusion partner in a salivary gland pleomorphic adenoma. In
      normal salivary gland tissue WIF1 is expressed at a high level and HMGA2 is not
      expressed. However, in the pleomorphic adenoma expressing the HMGA2/WIF1 fusion
      transcript, we observed re-expression of HMGA2 wild-type transcripts and very low
      levels of WIF1 expression. These data suggest a possible synergistic effect
      between upregulation of HMGA2 and downregulation of WIF1. We screened 13
      additional benign and malignant salivary gland tumors and detected WIF1
      rearrangement in one out of two carcinomas ex-pleomorphic adenoma analyzed. In
      this malignant tumor, the rearrangement of one WIF1 allele coexists with loss of
      the other allele, a classic signature of a tumor suppressor gene. WIF1 is an
      antagonist of the Wnt signaling pathway, which plays a critical role in human
      cancer. In transgenic mouse models, Wnt activation leads to a high frequency of
      benign and malignant salivary gland tumors. To our knowledge, this is the first
      report suggesting that WIF1 is a recurrent target in human salivary gland
      oncogenesis and that downregulation of WIF1 plays a role in the development
      and/or progression of pleomorphic adenomas.

PMID- 17171687
TI  - B-type natriuretic peptide as a marker for cardiac dysfunction in anthracycline
      treated children.
AB  - BACKGROUND: Anthracyclines (AC) are useful antineoplastic agents, whose utility
      is limited by progressive cardiotoxicity. Our purpose was to evaluate plasma B
      type natriuretic peptide (BNP), as a screening test for detecting late cardiac
      dysfunction in AC-treated children and to determine the prevalence of late
      cardiac dysfunction at low cumulative AC doses. MATERIALS AND METHODS: This was a
      prospective study in which patients who had completed AC therapy at least 1 year
      earlier, underwent a detailed echocardiogram and a simultaneous BNP level.
      Cardiac dysfunction was defined as any one of the following: shortening fraction
      (FS) <29%, rate corrected velocity of circumferential fiber shortening (VCFc)
      <0.9 c x sec(-1), end systolic wall stress (ESWS) >60 g x cm(-2), abnormal VCFc:
      ESWS ratio or decreased mitral inflow velocity (E/A) ratios, compared to age
      specific norms. RESULTS: The cohort (n = 63) included 37 males with a median age
      of 13.1 years (range, 6.5-26.5 years). Cardiac dysfunction was found in 26 (41%)
      patients and in 40% of patients who received cumulative doses <150 mg x m(-2).
      ESWS was the most common abnormality. Mean BNP levels in the subset with abnormal
      function were significantly higher than the normal group (23.4 +/- 25.3 vs. 14.2
      +/- 8.9 pg x ml(-1), P = 0.02). CONCLUSIONS: Plasma BNP was significantly
      elevated in AC-treated patients with late cardiac dysfunction, although there was
      considerable overlap of levels between groups with and without cardiac
      dysfunction. BNP may need further evaluation as a serial index of cardiac
      function in this population. Cardiac dysfunction was observed in a significant
      proportion of patients, even at low cumulative AC doses.

PMID- 17171688
TI  - Use of complementary and alternative medicine in children with cancer in
      Occidental, Mexico.
AB  - PURPOSE: To describe the types of complementary and alternative medicine (CAM)
      used by pediatric cancer patients attending a tertiary care hospital in Western
      Mexico. PATIENTS AND METHODS: In a cross-sectional survey, parents were
      interviewed and types of CAM employed as well as factors related to their use and
      their perceived effectiveness were determined. RESULTS: One hundred ten parents
      of pediatric cancer patients completed the survey. Seventy-seven patients (70%)
      received CAM. Of CAM used, herbal remedies (69%) and orally administered products
      (26%) were most common. Mean number of therapies was 2 +/- 1.1 (95% CI 1.59
      2.12). Prior CAM use by the family was associated with use in patients (P =
      0.006) (OR 4.6, CI 95% 1.7-12.9). Perceived usefulness was reported in 79% of CAM
      users. CONCLUSION: CAM use in Mexican children is common, most frequently with
      herbal therapies. The majority perceived benefits with its usage but in most
      cases, the treating physician was not informed about this practice.

PMID- 17171689
TI  - Splenectomy in children with idiopathic thrombocytopenic purpura: A prospective
      study of 134 children from the Intercontinental Childhood ITP Study Group.
AB  - BACKGROUND: Splenectomy is an effective procedure for children and adults with
      severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding
      pediatric patients are limited. PROCEDURE: Sixty-eight Intercontinental Childhood
      ITP Study Group (ICIS) investigators from 57 institutions in 25 countries
      participated in a splenectomy registry. Data from 153 patients were submitted, of
      whom 134 had a splenectomy and were analyzed. RESULTS: The median age at
      splenectomy was 11.8 (2.7-20.7) years. The median postsplenectomy follow-up was
      2.0 (0.1-4.5) years. Pre-splenectomy vaccination was not administered in 21
      children (15.7%). Open and laparoscopic splenectomy procedures were performed in
      67 and 65 evaluable children, respectively. Surgical technique was not reported
      in two children. Overall immediate platelet response to splenectomy was achieved
      in 113 patients (86.3%). Eighty percent of responders maintained their status of
      response during the following 4 years. Older age, longer duration of ITP, and
      male gender correlated with a complete response. Post-splenectomy sepsis was
      reported in seven patients without lethal outcome, although sepsis might be
      differently defined at participating institutions. CONCLUSIONS: Splenectomy is
      effective in children with ITP. Management varies greatly in different
      institutions. These Registry data may serve as a basis for future clinical trials
      to assess the indication and timing of splenectomy.

PMID- 17171690
TI  - Array CGH analysis in primary gastrointestinal stromal tumors: cytogenetic
      profile correlates with anatomic site and tumor aggressiveness, irrespective of
      mutational status.
AB  - Gastrointestinal stromal tumors (GISTs) comprise a biologically diverse group of
      neoplasms with respect to activating mutations in either KIT or PDGFRA,
      histology, anatomical site of origin, and clinical aggressiveness. In this study,
      we applied the high resolution array-based comparative genomic hybridization
      (array-CGH) technology to 66 primary GISTs (40 gastric and 26 nongastric, 48 with
      KIT and 18 with PDGFRA mutations) for identification of novel high-level
      alterations and for characterization of genotype-related genomic changes. All
      cases had genomic imbalances with the highest occurrence of 14q (73%), 1p (62%),
      22q (59%), 15q (38%), and 13q (29%) losses. Our data indicate that loss of
      chromosome 14 and/or 22 is an early change in GIST tumorigenesis irrespective of
      tumor genotype. Furthermore, DNA copy number changes showed a site dependent
      pattern. These included lower incidence of losses at 14q (87% vs. 35%), and
      higher frequency of losses at 1p (45% vs. 85%) and 15q (17% vs. 69%) in
      nongastric versus gastric site (P<0.001 for all). However, in the multivariate
      analysis with adjustment to tumor risk stratification, only the 14q loss site
      dependent pattern of distribution retained its significance. These findings
      suggest that loss of 14q is a relatively less frequent genetic event in the
      development of nongastric GISTs, the lack of which is most likely substituted by
      the accumulation of 1p/15q and other changes. The novel minimal overlapping
      regions of deletion at 1p (1p36.32-1p35.2, 1p34.1, and 1p22.1-1p21.3), 13q
      (13q14.11-q14.2 and 13q32.3-q33.1), and 15q23 were delineated, which point to
      chromosomal regions that may harbor genes relevant to the development of these
      neoplasms.

PMID- 17171692
TI  - Genetic susceptibility and body mass in childhood cancer survivors.
AB  - Childhood cancer survivors are at increased risk of many long-term treatment
      related sequel such as second cancers, cardiovascular disease, and pulmonary
      complications. Certain treatments seem to influence the risk of becoming
      overweight, obese, or underweight, and abnormal body mass index (BMI) is
      associated with increased morbidity and mortality. Because BMI is modifiable, it
      is important to identify treatment and patient-related factors contributing to
      altered BMI. New research areas include exploring how genetic susceptibility
      through population polymorphism may contribute to BMI. Illuminating potential
      gene-environment interactions that influence obesity and underweight might be
      more readily accomplished in a study of high-risk individuals (i.e., childhood
      cancer survivors) with well-characterized exposures. The new Childhood Cancer
      Research Network in the Children's Oncology Group, when fully implemented, should
      make it less difficult in the future to recruit the large numbers of patients
      needed for such studies.

PMID- 17171691
TI  - The M53I mutation in CDKN2A is a founder mutation that predominates in melanoma
      patients with Scottish ancestry.
AB  - Germline mutations in the tumor suppressor gene CDKN2A have been shown to
      predispose to cutaneous malignant melanoma. The M53I mutation is the most common
      CDKN2A mutation identified in Scottish melanoma patients and is also found in a
      small number of families in other countries. The aim of this study was to
      determine whether the occurrence of this mutation is due to a common ancestor
      originating from Scotland, and if so, to estimate how long ago the mutation
      arose. We examined 18 families carrying the M53I mutation: six from Scotland,
      five from Canada, four from Australia, and three from America. Haplotypes derived
      from segregation of seven informative microsatellite markers flanking CDKN2A were
      constructed in each family. Our findings show that 14 of 18 families carry a
      common ancestral haplotype on which the mutation arose approximately 88
      generations ago (1-LOD-unit support interval 44-198 generations). This haplotype
      is very rare in controls, which supports the idea that it is a common founder
      mutation haplotype. The four M53I families that do not share the consensus
      haplotype may in fact have arisen from the same founder, but this is potentially
      obscured by presumed replication slippage for some of the microsatellite markers
      tested.

PMID- 17171693
TI  - Childhood cancer in immigration population needs "AMOR" too.

PMID- 17171694
TI  - Essential versus reactive thrombocythemia in children: retrospective analyses of
      12 cases.
AB  - BACKGROUND: Essential thrombocythemia (ET) rarely occurs in the pediatric
      population and little is known about the clinical course and the molecular
      characteristics. PROCEDURE: In this retrospective multi-institutional study we
      examine the clinical, hematological, and molecular features of 12 children aged 5
      16 years with thrombocytosis and a suspected diagnosis of ET. RESULTS: Median
      follow-up was 59 months (range 10-72). Seven patients presented with clinical
      symptoms potentially related to thrombocytosis. The remaining five patients were
      diagnosed incidentally. Median platelet count at diagnosis was 1,325 x 10(9)/L
      (range 600-3,050). In 11 out of 12 cases bone marrow morphology was consistent
      with ET, the remaining patient had chronic idiopathic myelofibrosis. Cytogenetic
      analyses were normal in all studied cases and only one out of nine analyzed cases
      harbored a JAK(V617F) allele. Within 6 months after initial presentation one
      patient who was initially asymptomatic developed thrombosis and another patient
      had mild bleeding. Eight patients were treated with acetylsalicylic acid, one
      patient received hydroxyurea, and two patients received anagrelide. At last
      follow-up, all patients were alive and none had developed leukemia. Five patients
      experienced hematological remission. Two children had not received any therapy.
      During the course of their disease, nine patients developed symptoms possibly
      attributable to an elevated platelet count. CONCLUSIONS: In JAK2 mutation
      negative cases, long-term follow-up is helpful to distinguish between primary and
      secondary thrombocytosis. Secondary cases are not associated with organomegaly
      but may present with unspecific symptoms. Indications for treatment in children
      remain unclear.

PMID- 17171695
TI  - Survey of environmental enhancement programs for laboratory primates.
AB  - Animal welfare regulations in the United States require that nonhuman primate
      environmental enhancement plans be made in accordance with currently accepted
      professional standards; however, little information is available for quantifying
      common practice. Here we report the results of a 2003 survey that was sent to
      individuals overseeing enrichment programs at a variety of primate research
      institutions. The surveys requested information on program administration and
      management, implementation standards, procedures, and constraints pertaining to
      major categories of environmental enrichment, as well as intervention plans for
      animals exhibiting behavioral pathologies. Data were obtained on the management
      of 35,863 primates in 22 facilities. Behavioral scientists performed program
      oversight at the majority of facilities. Most programs reported recent changes,
      most commonly due to external site visits, and least commonly resulting from
      internal review. Most facilities' institutional animal care and use committees
      (IACUCs) included of individuals with behavioral expertise, and about two-thirds
      reported that enrichment issues could influence research protocol design. While
      most primates were reported to be housed socially (73%), social housing for
      indoor-housed primates appears to have changed little over the past 10 years.
      Research protocol issues and social incompatibility were commonly cited
      constraints. Implementation of feeding, manipulanda, and structural enrichment
      was relatively unconstrained, and contributions to these aspects of behavioral
      management generally included individuals in a wide variety of positions within a
      facility. In contrast, enrichment devices were used on a less widespread basis
      within facilities, and positive reinforcement programs that involved dedicated
      trainers were rare. We suggest that altering the role of the IACUC would be a
      productive avenue for increasing the implementation of social housing, and that
      an emphasis on prevention rather than intervention against behavioral pathology
      is warranted. The data from this survey may be useful for anticipating future
      program evaluations, establishing more effective internal evaluations, and
      assessing program progress and resource allocation.

PMID- 17171696
TI  - Comparison of diverged Hoxc8 early enhancer activities reveals modification of
      regulatory interactions at conserved cis-acting elements.
AB  - The Hoxc8 early enhancer that controls the initiation and establishment of Hoxc8
      expression in the developing mouse embryo is found in different vertebrate
      lineages including mammals, birds and fish. Mouse and Fugu Hoxc8 early enhancers
      (200 bp) have diverged in the composition of elements located towards the 3'
      region. However, they share cis-acting elements A-E located in the 5' region.
      Mutations at these elements in the context of the mouse Hoxc8 early enhancer
      affect reporter gene expression in the posterior neural tube, somites and lateral
      plate mesoderm of day 9.5 mouse embryos. Here, we demonstrate that mutations
      introduced at the same elements but in the context of the Fugu Hoxc8 early
      enhancer had different consequences on the reporter gene expression in transgenic
      mouse embryos. Furthermore, in contrast to the mouse enhancer the Fugu enhancer
      does not utilize elements D and E in achieving posterior neural tube and somite
      expression. These results suggest that the diverged sequences prevent regulatory
      interactions at conserved cis-acting elements. We propose that divergent
      sequences modify regulatory interactions at conserved elements by providing a
      "contextual change". Our finding that the enhancer elements do not act in a
      unitary fashion but function in the context of the surrounding sequence brings a
      new dimension to the study of cis-regulatory evolution.

PMID- 17171697
TI  - RNAs everywhere: genome-wide annotation of structured RNAs.
AB  - Starting with the discovery of microRNAs and the advent of genome-wide
      transcriptomics, non-protein-coding transcripts have moved from a fringe topic to
      a central field research in molecular biology. In this contribution we review the
      state of the art of "computational RNomics", i.e., the bioinformatics approaches
      to genome-wide RNA annotation. Instead of rehashing results from recently
      published surveys in detail, we focus here on the open problem in the field,
      namely (functional) annotation of the plethora of putative RNAs. A series of
      exploratory studies are used to provide non-trivial examples for the discussion
      of some of the difficulties.

PMID- 17171698
TI  - PCR survey of hox genes in the goldfish Carassius auratus auratus.
AB  - A tetraploidization event took place in the cyprinid lineage leading to
      goldfishes about 15 million years ago. A PCR survey for Hox genes in the goldfish
      Carassius auratus auratus (Actinopterygii: Cyprinidae) was performed to assess
      the consequences of this genome duplication. Not surprisingly, the genomic
      organization of the Hox gene clusters of goldfish is similar to that of the
      closely related zebrafish (Danio rerio). However, the goldfish exhibits a much
      larger number of recent pseudogenes, which are characterized by indels. These
      findings are consistent with the hypothesis that dosage effects cause selection
      pressure to rapidly silence crucial developmental regulators after a
      tetraploidization event.

PMID- 17171699
TI  - Calpain activity in retinal degeneration.
AB  - Retinal degenerations such as retinitis pigmentosa (RP) or glaucoma are a major
      cause of blindness in humans. Understanding the mechanisms underlying the various
      types of retinal degeneration is a pre-requisite for the development of rational
      therapies for these diseases. Activation of the calcium dependent protease,
      calpain, has been suggested to play an important role in cell death in various
      neuronal tissues including the retina. Improved detection and analysis of calpain
      activity during degenerative processes is likely to expand the list of
      pathological conditions with calpain involvement. We give a short overview of the
      methods available for the detection of calpain activity, and briefly discuss
      properties of calpain inhibitors. We then discuss the role of calpains in
      different cell death mechanisms and review existing work on retinal degeneration
      and the possible involvement of calpains therein. The implication of calpains in
      retinal cell death raises the possibility to use calpain inhibitors to prevent or
      delay retinal degeneration.

PMID- 17171700
TI  - Astroglia growth retardation and increased microglia proliferation by lithium and
      ornithine decarboxylase inhibitor in rat cerebellar cultures: Cytotoxicity by
      combined lithium and polyamine inhibition.
AB  - Lithium, the most prevalent treatment for manic-depressive illness, might have a
      neuroprotective effect after brain injury. In culture, lithium can exert
      neurotoxic effects associated with reduction in polyamine synthesis but
      neuroprotective effects as cultured neurons mature. Cumulative evidence suggests
      that lithium may exert some of its effects on neurons indirectly, by initially
      acting on glial cells. We used rat cerebellar cultures to ascertain the effects
      of lithium on ornithine decarboxylase (ODC) activity, the enzyme catalyzing the
      first step in polyamine synthesis, and to compare effects of lithium with those
      of the ODC inhibitor alpha-difluoromethylornithine (DFMO) on neuron survival and
      glial growth. Switching cultures from high (25 mM) to low (5 mM) KCl
      concentrations served as the traumatic neuronal insult. The results indicate the
      following. 1) Whereas high depolarizing KCl concentration enhances neuron
      survival, it inhibits astroglial growth. 2) Lithium (LiCl; 1-5 mM) enhances
      neuronal survival but inhibits astroglial growth. 3) Lithium treatment leads to
      reduced ODC activity. 4) DFMO enhances neuron survival but inhibits astroglial
      growth. 5) Lithium and DFMO lead to transformation of astroglia from epithelioid
      (flat) to process-bearing morphology and to increased numbers of microglia. 6)
      Combined lithium plus DFMO treatment is cytolethal to both neurons and glia in
      culture. In conclusion, lithium treatment results in growth retardation and
      altered cell morphology of cultured astroglia and increased microglia
      proliferation, and these effects may be associated with inhibition of polyamine
      synthesis. This implies that direct effects on astrocytes and microglia may
      contribute to the effects of lithium on neurons.

PMID- 17171701
TI  - Novel alternatively spliced endoplasmic reticulum retention signal in the
      cytoplasmic loop of Proteolipid Protein-1.
AB  - Increased awareness about the importance of protein folding and trafficking to
      the etiology of gain-of-function diseases has driven extensive efforts to
      understand the cell and molecular biology underlying the life cycle of normal
      secretory pathway proteins and the detrimental effects of abnormal proteins. In
      this regard, the quality-control machinery in the endoplasmic reticulum (ER) has
      emerged as a major mechanism by which cells ensure that secreted and
      transmembrane proteins either adopt stable secondary, tertiary, and quaternary
      structures or are retained in the ER and degraded. Here we examine cellular and
      molecular aspects of ER retention in transfected fibroblasts expressing missense
      mutations in the Proteolipid Protein-1 (PLP1) gene that cause mild or severe
      forms of neurodegenerative disease in humans. Mild mutations cause protein
      retention in the ER that is partially dependent on the presence of a
      cytoplasmically exposed heptapeptide, KGRGSRG. In contrast, retention associated
      with severe mutations occurs independently of this peptide. Accordingly, the
      function of this novel heptapeptide has a significant impact on pathogenesis and
      provides new insight into the functions of the two splice isoforms encoded by the
      PLP1 gene, PLP1 and DM-20.

PMID- 17171702
TI  - Methimazole-induced cell death in rat olfactory receptor neurons occurs via
      apoptosis triggered through mitochondrial cytochrome c-mediated caspase-3
      activation pathway.
AB  - The administration of methimazole is known to induce cell death in rat olfactory
      receptor neurons (ORNs). We investigated whether this injury occurs via apoptosis
      or through necrosis and whether it involves the extrinsic or intrinsic pathway.
      Rats were intraperitoneally injected with vehicle (control) or 300 mg/kg
      methimazole. The experimental animals were also administered vehicle or a caspase
      3 or caspase-9 inhibitor 30 min earlier. The administration of methimazole
      induced cell death predominantly in the mature ORNs and partially reduced
      olfactory sensitivity in the rats; the injured cells were TUNEL-positive and
      showed a nuclear staining pattern. This insult induced cytochrome c release from
      the mitochondria and a significant increase in the immunoreactivity of activated
      caspase-3 and caspase-9 as well as that of cleaved poly-ADP-ribose-polymerase; in
      addition, it caused a significant increase in the fluorogenic activity of caspase
      3 and caspase-9. However, it did not affect the immunoreactivity of activated
      caspase-8 or the fluorogenic activity of caspase-8. Pretreatment with a caspase-3
      or caspase-9 inhibitor nearly completely prevented the morphologic, biochemical,
      and functional changes induced by methimazole. These findings suggest strongly
      that methimazole-induced cell death in rat ORNs is predominantly apoptosis;
      moreover, the majority of this apoptotic cell death is triggered through
      mitochondrial cytochrome c-mediated caspase-3 activation pathway, and both
      caspase-3 and caspase-9 inhibitors can prevent methimazole-induced cell death in
      the ORNs.

PMID- 17171703
TI  - Glutathione elevation by gamma-glutamyl cysteine ethyl ester as a potential
      therapeutic strategy for preventing oxidative stress in brain mediated by in vivo
      administration of adriamycin: Implication for chemobrain.
AB  - Oxidative stress in heart and brain by the cancer chemotherapeutic drug
      adriamycin (ADR), used for treating solid tumors, is well established. Long-term
      treatment with ADR in breast cancer patients has led to symptoms of
      cardiomyopathy. Less well recognized, but increasingly well documented, is
      cognitive dysfunction. After chemotherapy, free radical-mediated oxidative stress
      has been reported in both heart and brain. We recently showed a significant
      increase in protein oxidation and lipid peroxidation in brain isolated from mice
      injected intraperitonially (i.p) with ADR. Systemic administration of ADR also
      induces tumor necrosis factor-alpha (TNF-alpha), which leads to production of
      reactive oxygen species (ROS) and reactive nitrogen species (RNS) in brain.
      Circulating TNF also causes mitochondrial dysfunction, leading to apoptotic
      pathways in brain. Inducible nitric oxide synthase also plays a role in ADR
      induced TNF-mediated neurotoxicity. In addition, we previously showed a
      significant decrease in glutathione (GSH) levels in brain isolated from ADR
      injected mice, along with increased expression of multidrug-resistant protein-1
      (MRP-1), glutathione-S-transferase (GST), glutathione peroxidase (GPx), and
      glutathione reductase (GR). There was a significant decrease in activity of brain
      GST. The present study was designed to test the hypothesis that, by elevating
      brain levels of GSH, the brain would be protected against oxidative stress in ADR
      injected mice. gamma-Glutamyl cysteine ethyl ester (GCEE), a precursor of
      glutathione, injected i.p. (150 mg/ kg body weight) 4 hr prior ADR injection (20
      mg/kg body weight) led to significantly decreased protein oxidation and lipid
      peroxidation in subsequently isolated mice brain compared with brain isolated
      from ADR-injected mice without GCEE. The GSH levels were restored to the level of
      brain isolated from saline-injected mice. Furthermore, the enzyme activity of GST
      was increased in brain isolated from ADR-injected mice previously injected with
      GCEE compared with the brain isolated from ADR-injected mice previously injected
      with saline. These results are discussed with regard to potential pharmacological
      prevention of brain cognitive dysfunction in patients receiving ADR chemotherapy.

PMID- 17171704
TI  - Prostate cancer progression in the presence of undetectable or low serum prostate
      specific antigen level.
AB  - BACKGROUND: The serum prostate-specific antigen (PSA) level after definitive
      treatment for prostate cancer (PC) is a powerful predictor of outcome.
      Occasionally, PC progression can occur despite low or undetectable PSA levels.
      The authors report on the clinical and pathologic characteristics of patients who
      experienced PC progression with undetectable or low PSA levels. METHODS: From an
      electronic database of all patients with PC who were treated at The University of
      Texas M. D. Anderson Cancer Center between 1999 and 2004, a group of 46 patients
      was identified who had progression to metastatic PC detected with concomitant PSA
      levels from 0.1 ng/mL to 2 ng/mL. Patient charts were reviewed for tumor stage,
      Gleason score, pretreatment PSA level, and the presence of atypical histologic
      variants (ie, ductal, sarcomatoid, or small cell cancers). The nadir PSA level
      after treatment and the PSA level at the time metastatic PC was detected were
      determined. The patients were followed semiannually, and imaging studies were
      obtained at the discretion of treating physicians. The sites of metastasis and
      histologic confirmation were reported when available. RESULTS: Twenty-three of 46
      patients underwent radical prostatectomy, 11 patients received radiation therapy,
      and 12 received hormone treatment as their initial form of therapy. Progression
      to metastatic disease with concomitant, undetectable PSA levels occurred in 10
      patients, including 3 patients who had not received treatment with hormones. The
      sites of metastasis included bone (n = 35 patients), liver (n = 7 patients),
      retroperitoneal lymph nodes (n = 5 patients), lungs (n = 4 patients), and brain
      (n = 1 patient). Aggressive and locally advanced PC were common features in these
      patients: Eighty-five percent had Gleason scores >or=7, 63% had clinical T3 or T4
      tumors, and 41% had pretreatment PSA levels >10 ng/mL. Atypical histologic
      variants were observed in 21 patients (46%) and in 8 of 10 patients who
      progressed with undetectable PSA levels. In 10 patients (22%), metastasis were
      detected in the presence of an undetectable PSA level. Eight of those patients
      had small cell carcinoma. In 19 patients (41%), progression to metastasis
      occurred without any increase in their PSA from the nadir level. Thirty-one
      patients (67%) were asymptomatic at the time metastasis was detected, and the
      detection of metastasis in these patients occurred only because of routine
      imaging studies. CONCLUSIONS: Progression of PC may occur despite undetectable or
      low PSA levels. Complete physical evaluation and imaging studies may be indicated
      in the surveillance of patients with high-grade, locally advanced tumors,
      especially when atypical histologic variants are present.

PMID- 17171705
TI  - Chronic rotenone treatment induces behavioral effects but no pathological signs
      of parkinsonism in mice.
AB  - It has been hypothesized that exposures to neurotoxic pesticides together with
      aging and genetic factors increase the risk for developing Parkinson's disease
      (PD) which is characterized by a progressive degeneration of the nigrostriatal
      dopaminergic pathway. Chronic treatment with the pesticide rotenone has been
      reported to induce parkinsonism in rats. Although transgenic mice (but not
      transgenic rats) are available to investigate the importance of environmental
      factors in genetically predisposed animals, the effects of chronic rotenone
      exposure have so far not been examined in intact mice. Therefore, we investigated
      the effects of chronic exposure to rotenone (2.5 or 4.0-5.0 mg/kg s.c. for 30-45
      days) in mice aged 2.5, 5, or 12 months. During the treatment period, the effects
      on vitality and motor behavior were investigated. Furthermore, the toxicity of
      rotenone on dopaminergic nigrostriatal neurons and peripheral tissues was
      examined. In comparison with control mice, rotenone-treated mice had a decreased
      spontaneous motor activity, but the density of nigral dopaminergic neurons failed
      to show any significant changes, except for a tendency to decrease in old mice
      treated with 4 mg/kg. At the tested doses, rotenone caused a moderate hepatic
      fatty degeneration. The data indicate that rotenone is not able to cause the
      neuropathological characteristics of PD in mice under these testing paradigms,
      which were similar to those of the rotenone rat model. Further studies will have
      to clarify whether genetic mouse models of PD might be more sensitive to the
      neurotoxic effects of rotenone.

PMID- 17171706
TI  - Overexpression of hippocampal Ca2+/calmodulin-dependent protein kinase II
      improves spatial memory.
AB  - Hippocampal alpha-calcium/calmodulin-dependent protein kinase II (alphaCaMKII)
      has been implicated in neuronal plasticity and spatial learning. In the present
      experiment, an adeno-associated virus (AAV) vector was designed to express
      alphaCaMKII driven by the U6 promotor. Microinfusion of this vector into the rat
      hippocampus increased alphaCaMKII immunoreactivity by approximately 73% (Western
      analysis) and improved performance in a water maze task. Locomotor activity and
      exploratory behavior in an open field task were not altered by the overexpression
      of alphaCaMKII. These data support a role for alphaCaMKII in spatial or explicit
      memory storage. The advantages of viral vectors for manipulating target proteins
      expression compared with genetically modified mouse models are discussed.

PMID- 17171707
TI  - Inhibin may be involved in negative feedback in the prairie dog (Cynomys
      ludovicianus).
AB  - The changes in inhibin immunostaining in the gonads during the annual
      reproductive cycle of both sexes of the prairie dog are described. No inhibin
      immunostaining was found in primary or secondary follicles of the ovary. Theca
      and granulosa cells of preovulatory Graafian follicles found in January and
      February stained for inhibin. Corpora lutea of both pregnant and non-pregnant
      females stain more densely for inhibin than follicles. Inhibin staining is
      present in luteal cells for at least 4 months during regression, longer than
      detectable progesterone is secreted. Sertoli cells in the testes do not have
      inhibin immunostaining during recrudescence. These cells show light immunostain
      for inhibin during peak spermatogenic activity in January and February but stain
      more deeply during early regression of the testis. Stain is gradually lost in the
      next 4-5 months as the tubules close. Leydig cells and germ cells do not stain
      for inhibin at any stage of the annual cycle but interstitial cells and tunic
      cells stain during the breeding phase. The presence of immunochemical staining
      for inhibin in prairie dog gonads during regression suggests that inhibin is part
      of a negative feedback complex that includes progesterone in the female and
      testosterone or another androgen in the male. Negative feedback during regression
      may also cause gonadal inactivity.

PMID- 17171708
TI  - Bleomycin-induced DNA damage and repair in Xenopus laevis and Xenopus tropicalis.
AB  - Microgel cell electrophoresis has been used with various species to measure
      breakage of DNA and DNA repair following exposure to the radiomimetic antibiotic,
      bleomycin. With humans, a high degree of DNA damage is considered to be
      predictive of cancer susceptibility. Non-isogeneic Xenopus laevis, the South
      African clawed toad, rarely develop spontaneous or induced cancers. Here, we
      investigate bleomycin-induced DNA damage and repair in splenic lymphocytes of
      this species to test consistency with cancer predictability. As X. laevis is
      pseudotetraploid in nature, while Xenopus tropicalis is diploid, we additionally
      explore the effect of polyploidy on DNA damage and repair in these vertebrates.
      The results show that higher doses of bleomycin are required to induce comparable
      levels of DNA damage in both Xenopus species, than in humans. X. tropicalis, the
      diploid, is more bleomycin-sensitive than is X. laevis. Additionally, repair
      rates of damaged DNA of X. laevis lymphocytes are more rapid than those of X.
      tropicalis, although both are hours slower than human leukocytes. While no data
      exist on cancer susceptibility in X. tropicalis, the results suggest greater
      susceptibility to cancer than X. laevis, but less than in humans. Thus,
      polyploidy serves as a protection against DNA damage and allows more rapid
      repair.

PMID- 17171709
TI  - Correlated response in yolk testosterone levels following divergent genetic
      selection for social behaviour in Japanese quail.
AB  - Maternal effects are a powerful tool that parents can use to modify the phenotype
      of their offspring. In birds, the amount of androgens that females deposit in
      their eggs has been shown to influence early development and adult behavioural
      phenotypes. Differences in such behavioural strategies have been used as the
      target of artificial selection programmes with a view to improve animal welfare.
      In this study, we tested whether artificial selection for divergent social
      behaviour in Japanese quail had resulted in correlated changes in yolk androgen
      levels. We used lines that had been selected at the chick stage for high and low
      motivation to regain contact with a group of conspecific chicks. This procedure
      has led to important behavioural differences in the high and low line in a suite
      of behavioural correlates of sociality. We found that eggs laid by the line
      selected for high motivation for social reinstatement contained more than twice
      the amount of yolk testosterone of eggs laid by females from the low line, while
      the unselected line laid eggs with intermediate levels. This finding strongly
      suggests a functional link between these two traits, and underlines the possible
      role of yolk androgen modulation in promoting the evolution of behavioural
      syndromes.

PMID- 17171710
TI  - Autoradiographic localization of aromatic hydrocarbon receptor (AHR) in rhesus
      monkey ovary.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic congener of a large
      class of manmade pollutants that persist in the environment. TCDD exerts its
      toxic effects, in part, by binding to its receptor known as the aromatic
      hydrocarbon receptor (AHR). TCDD is estrogen modulatory and in some systems its
      receptor associates directly with estrogen receptors via co-activator molecules.
      TCDD inhibits steroid synthesis in human ovarian granulosa cells and AHR is found
      in these cells. We have previously shown that AHR is found in whole rhesus monkey
      ovary, but have yet to establish its location. In the present study, we set out
      to show that radiolabeled TCDD binds to monkey ovarian follicles and that this
      binding is receptor mediated. Ovaries from Macaca mulatta were sectioned on a
      cryostat at 10 micro m; and sections were incubated with either control vehicle,
      (3)H-TCDD, or (3)H-TCDD plus alpha-naphthoflavone (ANF), a known receptor
      blocking agent. Here, we show for the first time specific binding of TCDD to the
      granulosa cells of antral follicles and other regions of the rhesus monkey ovary.
      Our data indicate a 60-fold increase in binding with (3)H-TCDD over that of
      control, and that this binding is reduced to the levels seen in controls with the
      addition of the competitive antagonist ANF. These findings support the hypothesis
      that TCDD directly affects primate ovarian function via the AHR.

PMID- 17171711
TI  - Decreased pCO(2) accumulation by eliminating bicarbonate addition to high cell
      density cultures.
AB  - High-density perfusion cultivation of mammalian cells can result in elevated
      bioreactor CO(2) partial pressure (pCO(2)), a condition that can negatively
      influence growth, metabolism, productivity, and protein glycosylation. For BHK
      cells in a perfusion culture at 20 x 10(6) cells/mL, the bioreactor pCO(2)
      exceeded 225 mm Hg with approximate contributions of 25% from cellular
      respiration, 35% from medium NaHCO(3), and 40% from NaHCO(3) added for pH
      control. Recognizing the limitations to the practicality of gas sparging for
      CO(2) removal in perfusion systems, a strategy based on CO(2) reduction at the
      source was investigated. The NaHCO(3) in the medium was replaced with a MOPS
      Histidine buffer, while Na(2)CO(3) replaced NaHCO(3) for pH control. These
      changes resulted in 63-70% pCO(2) reductions in multiple 15 L perfusion
      bioreactors, and were reproducible at the manufacturing-scale. Bioreactor pCO(2)
      values after these modifications were in the 68-85 mm Hg range, pCO(2) reductions
      consistent with those theoretically expected. Low bioreactor pCO(2) was
      accompanied by both 68-123% increased growth rates and 58-92% increased specific
      productivity. Bioreactor pCO(2) reduction and the resulting positive implications
      for cell growth and productivity were brought about by process changes that were
      readily implemented and robust. This philosophy of pCO(2) reduction at the source
      through medium and base modification should be readily applicable to large-scale
      fed-batch cultivation of mammalian cells.

PMID- 17171712
TI  - Rhesus macaques (Macaca mulatta) are not neophobic toward novel food with a high
      sugar content.
AB  - While we know that food neophobia in nonhuman primates is affected by social
      factors, little is known about how palatability, and specifically sugar content,
      might ameliorate a monkey's hesitancy to eat a novel food. It is likely that an
      innate preference for sweet substances would alter an animal's typical neophobic
      response. To test this, I presented nine male rhesus macaques with novel foods
      that contained a low, high, or no amount of sugar. As expected, the monkeys
      exhibited a neophobic response to the no-sugar novel foods but not to the high
      sugar novel foods. Previous research on food neophobia may need to be reevaluated
      in light of the effects of sugar content on the neophobic response.

PMID- 17171713
TI  - Patterns of dispersal in Sumatran siamangs (Symphalangus syndactylus):
      preliminary mtDNA evidence suggests more frequent male than female dispersal to
      adjacent groups.
AB  - Gibbons of both sexes have been observed emigrating from their natal groups, but
      the consequences of dispersal in gibbons are poorly understood, and it is unclear
      whether these are the same for both sexes. I sequenced a 350-bp fragment of
      mitochondrial DNA from 18 adults in seven siamang (Symphalangus syndactylus)
      groups at the Way Canguk Research Station in southern Sumatra to assess patterns
      of matrilineal relatedness among and within siamang groups, and to assess their
      fit with different patterns of sex-specific dispersal. A total of 11 haplotypes
      were identified in the seven study groups; 50% of adult males in five contiguous
      groups shared a haplotype with a member of an immediately adjacent group, whereas
      only 16.7% of females shared a haplotype with a neighbor. The apparent difference
      persisted if only same-sex individuals were considered (37.5% of males vs. 0% of
      females). Four of the seven study groups contained two adult males and a single
      adult female. In three multimale groups, the three adults all had different
      haplotypes, suggesting that neither male was the retained adult offspring of the
      female, whereas in the fourth group, the haplotype of one male was identical with
      that of the adult female. The high diversity of haplotypes and the absence of
      clustering among female haplotypes in the study neighborhood suggest that female
      dispersal to territories adjacent to the natal group may be relatively rare. The
      presence of some clustering of male haplotypes suggests that shorter dispersal
      distances may be more common in males.

PMID- 17171714
TI  - Glutamatergic synaptic depression by synthetic amyloid beta-peptide in the medial
      septum.
AB  - The medial septum/diagonal band region, which participates in learning and memory
      processes via its cholinergic and GABAergic projection to the hippocampus, is one
      of the structures affected by beta amyloid (betaA) deposition in Alzheimer's
      disease (AD). The acute effects of betaA (25-35 and 1-40) on action potential
      generation and glutamatergic synaptic transmission in slices of the medial septal
      area of the rat brain were studied using current and patch-clamp techniques. The
      betaA mechanism of action through M1 muscarinic receptors and voltage-dependent
      calcium channels was also addressed. Excitatory evoked responses decreased (30
      60%) in amplitude after betaA (2 microM) perfusion in 70% of recorded cells.
      However, the firing properties were unaltered at the same concentration. This
      depression was irreversible in most cases, and was not prevented or reversed by
      nicotine (5 microM). In addition, the results obtained using a paired-pulse
      protocol support pre- and postsynaptic actions of the peptide. The betaA effect
      was blocked by calcicludine (50 nM), a selective antagonist of L-type calcium
      channels, and also by blocking muscarinic receptors with atropine (5 muM) or
      pirenzepine (1 microM), a more specific M1-receptor blocker. We show that in the
      medial septal area this oligomeric peptide acts through calcium channels and
      muscarinic receptors. As blocking any of these pathways blocks the betaA effects,
      we propose a joint action through both mechanisms. These results may contribute
      to a better understanding of the pathophysiology at the onset of AD. This
      understanding will be required for the development of new therapeutic agents.

PMID- 17171715
TI  - Optimization of heterologous production of the polyketide 6-MSA in Saccharomyces
      cerevisiae.
AB  - Polyketides are a group of natural products that have gained much interest due to
      their use as antibiotics, cholesterol lowering agents, immunosuppressors, and as
      other drugs. Many organisms that naturally produce polyketides are difficult to
      cultivate and only produce these metabolites in small amounts. It is therefore of
      general interest to transfer polyketide synthase (PKS) genes from their natural
      sources into heterologous hosts that can over-produce the corresponding
      polyketides. In this study we demonstrate the heterologous expression of 6
      methylsalicylic acid synthase (6-MSAS), naturally produced by Penicillium
      patulum, in the yeast Saccharomyces cerevisiae. In order to activate the PKS a 4'
      phosphopantetheinyl transferase (PPTase) is required. We therefore co-expressed
      PPTases encoded by either sfp from Bacillus subtilis or by npgA from Aspergillus
      nidulans. The different strains were grown in batch cultures. Growth and product
      concentration were measured and kinetic parameters were calculated. It was shown
      that both PPTases could be efficiently used for activation of PKS's in yeast as
      good yields of 6-MSA were obtained with both enzymes.

PMID- 17171716
TI  - Direct solubilization of enzyme aggregates with enhanced activity in nonaqueous
      media.
AB  - A protein solubilization method has been developed to directly solubilize protein
      clusters into organic solvents containing small quantities of surfactant and
      trace amounts of water. Termed "direct solubilization," this technique was shown
      to solubilize three distinct proteins - subtilisin Carlsberg, lipase B from
      Candida antarctica, and soybean peroxidase - with much greater efficiencies than
      extraction of the protein from aqueous solution into surfactant-containing
      organic solvents (referred to as extraction). More significant, however, was the
      dramatic increase in directly solubilized enzyme activity relative to extracted
      enzyme activity, particularly for subtilisin and lipase in polar organic
      solvents. For example, in THF the initial rate towards bergenin
      transesterification was ca. 70 times higher for directly solubilized subtilisin
      than for the extracted enzyme. Furthermore, unlike their extracted counterparts,
      the directly solubilized enzymes yielded high product conversions across a
      spectrum of non-polar and polar solvents. Structural characterization of the
      solubilized enzymes via light scattering and atomic force microscopy revealed
      soluble proteins consisting of active enzyme aggregates containing approximately
      60 and 100 protein molecules, respectively, for subtilisin and lipase. Formation
      of such clusters appears to provide a microenvironment conducive to catalysis
      and, in polar organic solvents at least, may protect the enzyme from solvent
      induced inactivation.

PMID- 17171717
TI  - Short-term temperature effects on the anaerobic metabolism of glycogen
      accumulating organisms.
AB  - Proliferation of glycogen accumulating organisms (GAO) has been identified as a
      potential cause of enhanced biological phosphorus removal (EBPR) failure in
      wastewater treatment plants (WWTP). GAO compete for substrate with polyphosphate
      accumulating organisms (PAO) that are the microorganisms responsible for the
      phosphorus removal process. In the present article, the effects of temperature on
      the anaerobic metabolism of GAO were studied in a broad temperature range (from
      10 to 40 degrees C). Additionally, maximum acetate uptake rate of PAO, between 20
      and 40 degrees C, was also evaluated. It was found that GAO had clear advantages
      over PAO for substrate uptake at temperatures higher than 20 degrees C. Below 20
      degrees C, maximum acetate uptake rates of both microorganisms were similar.
      However, lower maintenance requirements at temperature lower than 30 degrees C
      give PAO metabolic advantages in the PAO-GAO competition. Consequently, PAO could
      be considered to be psychrophilic microorganisms while GAO appear to be
      mesophilic. These findings contribute to understand the observed stability of the
      EBPR process in WWTP operated under cold weather conditions. They may also
      explain the proliferation of GAO in WWTP and thus, EBPR instability, observed in
      hot climate regions or when treating warm industrial effluents. It is suggested
      to take into account the observed temperature dependencies of PAO and GAO in
      order to extend the applicability of current activated sludge models to a wider
      temperature range.

PMID- 17171718
TI  - Enhanced protein production by engineered zinc finger proteins.
AB  - Increasing the yield of therapeutic proteins from mammalian production cell lines
      reduces costs and decreases the time to market. To this end, we engineered a zinc
      finger protein transcription factor (ZFP TF) that binds a DNA sequence within the
      promoter driving transgene expression. This ZFP TF enabled >100% increase in
      protein yield from CHO cells in transient, stable, and fermentor production run
      settings. Expression vectors engineered to carry up to 10 ZFP binding sites
      further enhanced ZFP-mediated increases in protein production up to approximately
      500%. The multimerized ZFP binding sites function independently of the promoter,
      and therefore across vector platforms. CHO cell lines stably expressing ZFP TFs
      demonstrated growth characteristics similar to parental cell lines. ZFP TF
      expression and gains in protein production were stable over >30 generations in
      the absence of antibiotic selection. Our results demonstrate that ZFP TFs can
      rapidly and stably increase protein production in mammalian cells.

PMID- 17171719
TI  - Fermentation of biomass-generated synthesis gas: effects of nitric oxide.
AB  - The production of renewable fuels, such as ethanol, has been steadily increasing
      owing to the need for a reduced dependency on fossil fuels. It was demonstrated
      previously that biomass-generated synthesis gas (biomass-syngas) can be converted
      to ethanol and acetic acid using a microbial catalyst. The biomass-syngas
      (primarily CO, CO(2), H(2), and N(2)) was generated in a fluidized-bed gasifier
      and used as a substrate for Clostridium carboxidivorans P7(T). Results showed
      that the cells stopped consuming H(2) when exposed to biomass-syngas, thus
      indicating that there was an inhibition of the hydrogenase enzyme due to some
      biomass-syngas contaminant. It was hypothesized that nitric oxide (NO) detected
      in the biomass-syngas could be the possible cause of this inhibition. The
      specific activity of hydrogenase was monitored with time under varying
      concentrations of H(2) and NO. Results indicated that NO (at gas concentrations
      above 40 ppm) was a non-competitive inhibitor of hydrogenase activity, although
      the loss of hydrogenase activity was reversible. In addition, NO also affected
      the cell growth and increased the amount of ethanol produced. A kinetic model of
      hydrogenase activity with inhibition by NO was demonstrated with results
      suggesting there are multiple binding sites of NO on the hydrogenase enzyme.
      Since other syngas-fermenting organisms utilize the same metabolic pathways, this
      study estimates that NO < 40 ppm can be tolerated by cells in a syngas
      fermentation system without compromising the hydrogenase activity, cell growth,
      and product distribution.

PMID- 17171720
TI  - Survival and apoptotic pathways initiated by TNF-alpha: modeling and predictions.
AB  - We present a mathematical model which includes TNF-alpha initiated survival and
      apoptotic cascades, as well as nuclear transcription of IkappaB. These pathways
      play a crucial role in deciding cell fate in response to inflammation and
      infection. Our model incorporates known specific protein-protein interactions as
      identified by experiments. Using these biochemical interactions, we develop a
      mathematical model of the NF-kappaB-mediated survival and caspase-mediated
      apoptosis pathways. Using mass action kinetics, we follow the formation of the
      survival and late complexes as well as the dynamics of DNA fragmentation. The
      effect of TNF-alpha concentration on DNA fragmentation is modeled and compares
      well with experiment. Nuclear transcription is also modeled phenomenologically by
      means of time lagged cytosolic concentrations. This results in transcription
      related concentrations undergoing under-damped oscillations, in qualitative and
      quantitative agreement with experiment. Using a tumor cell as a hypothetical
      model, we explore the interplay between the components of the survival and
      apoptotic pathways. Results are presented which make predictions on the limits of
      cellular oscillations in terms of time delay, initial concentration ratios and
      other features of the model. The model also makes clear predictions on cell
      viability in terms of DNA damage within the framework of TNF-alpha stimulus
      duration.

PMID- 17171721
TI  - Development of a 3D cell culture system for investigating cell interactions with
      electrospun fibers.
AB  - There are many variables to be considered in studying how cells interact with 3D
      scaffolds used in tissue engineering. In this study we investigated the influence
      of the fiber diameter and interfiber spaces of 3D electrospun fiber scaffolds on
      the behavior of human dermal fibroblasts. Fibers of two dissimilar model
      materials, polystyrene and poly-L-lactic acid, with a broad range of diameters
      were constructed in a specifically developed 3D cell culture system. When
      fibroblasts were introduced to freestanding fibers, and encouraged to "walk the
      plank," a minimum fiber diameter of 10 microm was observed for cell adhesion and
      migration, irrespective of fiber material chemistry. A distance between fibers of
      up to 200 microm was also observed to be the maximum gap that could be bridged by
      cell aggregates--a behavior not seen in conventional 2D culture. This approach
      has identified some basic micro-architectural parameters for electrospun scaffold
      design and some key differences in fibroblast growth in 3D. We suggest the
      findings will be of value for optimizing the integration of cells in these
      scaffolds for skin tissue engineering.

PMID- 17171722
TI  - Performance of potential non-crop or wild species under OECD 208 testing
      guideline study conditions for terrestrial non-target plants.
AB  - The inclusion of 52 potential non-crop or wild species in new OECD guidelines for
      terrestrial non-target plant (TNTP) testing led to a ring test conducted by four
      laboratories experienced in regulatory testing. Species selected had shown
      potential to meet validity criteria of emergence for TNTP studies in a previous
      evaluation of the 52 species. OECD 208 guideline conditions were applied, with
      and without seed pretreatments recommended to enhance germination. These species
      were Abutilon theophrasti (L.) Medic., Avena fatua L., Fallopia convolvulus (L.)
      Adans., Galium aparine L., Ipomoea hederacea (L.) Jacq. and Veronica persica
      Poir. Only I. hederacea met the validity criterion of 70% emergence in all
      laboratories and showed a low variability in biomass. Of the other species, none
      led to 70% emergence in all four laboratories. The recommended pretreatments did
      not have a major impact on emergence. Biomass was also investigated with A.
      theophrasti, A. fatua, Centaurea cyanus L., I. hederacea and Rumex crispus L.
      Variability of biomass, a key parameter in TNTP regulatory studies, exceeded
      normal biomass variability of crop species used for TNTP studies. The addition of
      a thin layer of quartz sand to the soil surface resulted in improved emergence of
      C. cyanus, G. aparine and V. persica; however, such a procedure, while routine in
      screening studies to improve germination, is a deviation from the TNTP
      guidelines. These initial studies indicate that some species could meet the
      emergence criteria for TNTP testing. However, there is a need for further studies
      on seed source, seed quality and conditions for uniform emergence before their
      use in routine regulatory testing.

PMID- 17171723
TI  - Resilience and well-being in palliative care staff: a qualitative study of
      hospice nurses' experience of work.
AB  - Although working with cancer patients is considered stressful, palliative care
      staff experience similar levels of psychological distress and lower levels of
      burnout than staff working in other specialties. There are few empirical studies
      in palliative care to explain this. Since working in a stressful job does not
      inevitably lead to psychological distress, the antecedent factors that promote
      resilience and maintain a sense of well-being are worthy of study. This
      qualitative study used interpretative phenomenological analysis (IPA) to describe
      hospice nurses' experiences of work. During the analysis, themes emerged relating
      to the underlying interpersonal factors that influenced the nurses' decisions to
      begin and continue working in palliative care, and their attitudes towards life
      and work. The emergent themes were compared with the theoretical personality
      constructs of hardiness and sense of coherence, and this comparison highlighted
      many similarities. The nurses showed high levels of commitment, and imputed a
      sense of meaning and purpose to their work. An area of divergence was their
      response to change, and this is discussed in relation to hardiness and sense of
      coherence. The implications for staff well-being, and for staff training and
      support, which, in turn, may impact on the quality of patient care, are
      discussed.

PMID- 17171724
TI  - Free-radical pathways in the decomposition of ketones over polycrystalline
      TiO(2): the role of organoperoxy radicals.
AB  - The oxidative decomposition of various ketones (including acetone, 2-butanone, 4
      heptanone, cyclopentanone and cyclohexanone) over dehydrated TiO(2) (P25) powder
      is investigated by electron paramagnetic resonance (EPR) spectroscopy. For the
      first time, a series of thermally unstable radical intermediates are observed
      both on the activated and reduced TiO(2) surface, depending on the adopted
      experimental conditions. These radical intermediates are identified as
      organoperoxy-based species of general formula ROO(.-) and RCO(3) (.-). They are
      formed by reaction of photogenerated charge carriers (either trapped electrons or
      trapped holes) with the adsorbed ketones in the presence of molecular oxygen. The
      organoperoxy intermediates are thermally unstable and decompose at temperatures
      in the region of 180-250 K. This work demonstrates that free-radical pathways
      involving both organoperoxy and superoxide radicals can be responsible for the
      thermal- and photodecomposition of ketones over polycrystalline TiO(2) (P25).

PMID- 17171725
TI  - Cages and needles of group 13-15 binary hydrides.

PMID- 17171726
TI  - Supramolecular dye laser with cucurbit[7]uril in water.

PMID- 17171727
TI  - Metallo-organic domino reactions: C-H versus C-C bond breaking.
AB  - HL and MeL are prepared by condensing benzil dihydrazone with 2-formylpyridine
      and 2-acetylpyridine, respectively, in 1:2 molar proportions. While in a reaction
      with [Ru(C(6)H(6))Cl(2)]2, HL yields the cation [Ru(C(6)H(6)){5,6-diphenyl-3
      (pyridin-2-yl)-1,2,4-triazine}Cl]+, MeL gives the cation [Ru(C(6)H(6))(MeL)Cl]+.
      Both the cations are isolated as their hexafluorophosphate salts and
      characterised by X-ray crystallography. In the case of HL, double domino
      electrocyclic/elimination reactions are found to occur. The electrocyclic
      reaction occurs in a C=N-N=C-C=N fragment of HL and the elimination reaction
      involves breaking of a C-H bond of HL. Density functional calculations on model
      complexes indicate that the identified electrocyclic reaction is thermochemically
      as well as kinetically feasible for both HL and MeL in the gas phase. For a
      double domino reaction, similar to that operative in HL, to occur for MeL,
      breaking of a C-C bond would be required in the elimination step. Our model
      calculations show the energy barrier for this elimination step to be much higher
      (329.1 kJ mol(-1)) for MeL than that for HL (96.3 kJ mol(-1)). Thus, the domino
      reaction takes place for HL and not for MeL. This accounts for the observed
      stability of [Ru(C(6)H(6))(MeL)Cl]+ under the reaction conditions employed.

PMID- 17171728
TI  - Tuning the electronic communication in heterobimetallic mixed-valence ions of (1
      ferrocenyl)- and (2-ferrocenyl)indenyl rhodium isomers.
AB  - A series of heterobimetallic complexes of general structure [RhL(2){eta(5)-(2
      ferrocenyl)indenyl}] (L(2)=cod, nbd, L=CO; cod=cyclooctadiene; nbd=norbornadiene)
      has been synthesised with the aim of tuning the metal-metal interaction in their
      mixed-valence ions generated both by chemical and electrochemical oxidation, and
      the results are compared with those obtained for [RhL(2){eta(5)-(1
      ferrocenyl)indenyl}] isomers. Crystallographic studies and DFT calculations
      provide a detailed description of the structural and electronic features of these
      complexes evidencing a significant difference in the extent of planarity of the
      flexible bridging ligand between the 1- and 2-ferrocenyl isomers. Independent
      experimental probes, in particular the potential splitting in the cyclic
      voltammograms and the IT bands in the near-IR spectra, are rationalised in the
      framework of Marcus-Hush theory and at quantum chemistry level by DFT and TD-DFT
      methods. These methods allow us to establish a trend based on the magnitude of
      iron-rhodium electronic coupling H(ab) ranging from valence trapped to almost
      delocalised ions. The quasi planar bridge and the olefin ancillary ligands make
      [Rh(nbd){eta(5)-(2-ferrocenyl)indenyl}](+) and [Rh(cod){eta(5)-(2
      ferrocenyl)indenyl}](+) rare examples of heterobimetallic systems which can be
      classified as borderline Class II/Class III species.

PMID- 17171729
TI  - Separation of olefin/paraffin mixtures using zwitterionic silver complexes as
      transport carriers.
AB  - Zwitterionic silver nitrate salts of 1-(1-methyl-3-imidazolio)propane-3
      sulfonate, 1-(1-methyl-1-pyrrolidinio)propane-3-sulfonate, and 1-(4-methyl-4
      morpholio)propane-3-sulfonate have been prepared and tested as carriers for
      facilitated olefin transport membranes in the separation of ethylene/ethane,
      propylene/propane, and C4 mixtures. The interactions of olefins with silver ions
      bound to sulfonate groups were investigated by FTIR spectroscopy as well as the
      correlation between the binding affinity of olefins and facilitated transport.

PMID- 17171730
TI  - Iridium(I) pyridyl azolate complexes with saturated red metal-to-ligand charge
      transfer phosphorescence; fundamental and potential applications in organic light
      emitting diodes.
AB  - Preparation of a new series of neutral metal complexes [(cod)Ir(fppz)] (1),
      [(cod)Ir(bppz)] (2), [(cod)Ir(fptz)] (3) and [(cod)Ir(bptz)] (4), bearing one cod
      ligand and a pyridyl azolate chelate are reported. A single-crystal X-ray
      diffraction study of 3 reveals the expected distorted square-planar geometry. The
      lowest absorption band consists of IrI atom increased triplet dpi-->pi*
      transitions (3MLCT), the assignment of which is firmly supported by the
      theoretical approaches. Complexes 1-4 exhibit weak phosphorescence in degassed
      solution at room temperature, whereas much more intense, solid-state
      phosphorescence appears in the range 622-649 nm. The pure MLCT emission was used
      as a prototypical model to address its remarkable spectral differences from the
      IrIII isoquinoline pyrrolide complex (5), which has mainly 3pipi phosphorescence.
      Complex 3 was used as a dopant to fabricate red-emitting phosphorescent organic
      light-emitting diodes (OLEDs). For the 7 % doped device, a maximum brightness of
      3010 cd m-2 was achieved at an applied voltage of 15 V and with CIE coordinates
      of (0.56, 0.33), demonstrating for the first time the potential of neutral IrI
      complexes in OLED applications.

PMID- 17171731
TI  - Arene complexes of beta-diketiminato supported organoscandium cations: mechanism
      of arene exchange and alkyne insertion in solvent separated ion pairs.
AB  - A family of isolable solvent separated organoscandium methyl cations stabilized
      by beta-diketiminato ligands (Ar)NC(CH3)CHC(CH3)N(Ar) (Ar=2,6-iPr-C6H3, LMe) has
      been prepared by reaction of LMeScR2 with [CPh3][B(C6F5)4] in the presence of an
      arene solvent. Arenes such as bromobenzene, benzene, toluene, para-xylene and
      mesitylene bind the scandium center in an eta6-bonding mode, yielding cations 1 a
      e. Their solution and solid-state structures have been explored using
      multinuclear NMR spectroscopy and X-ray crystallography. Mechanistic studies on
      arene exchange reactions and the insertion of diphenylacetylene indicate that
      these processes occur via arene intermediates of lower hapticity, followed by
      binding of the incoming reagent. Which of the two steps is rate limiting depends
      on the arene being displaced and/or the nature of the incoming substrate. The
      experiments present a unified view of these mechanisms, which have relevance to
      propagation processes in olefin polymerizations mediated by such cations.

PMID- 17171732
TI  - Anion-directed self-assembly of lanthanide-notp compounds and their fluorescence,
      magnetic, and catalytic properties.
AB  - Reactions of 1,4,7-triazacyclononane-1,4,7-triyl-tris(methylenephosphonic acid)
      [notpH(6), C(9)H(18)N(3)(PO(3)H(2))3] with different lanthanide salts result in
      four types of Ln-notp compounds:
      [Ln{C(9)H(20)N(3)(PO(3)H)(2)(PO(3))}(NO(3))(H(2)O)].4H2O (1), [Ln = Eu (1 Eu), Gd
      (1 Gd), Tb (1 Tb)], [Ln{C(9)H(20)N(3)(PO(3)H)(2)(PO(3))}(H2O)]Cl.3H2O (2) [Ln =
      Eu (2 Eu), Gd (2 Gd), Tb (2 Tb)],
      [Ln{C(9)H(20)N(3)(PO(3)H)(2)(PO(3))}(H2O)]ClO4.8H2O, (3) [Ln = Eu (3 Eu), Gd (3
      Gd)], and [Ln{C(9)H(20)N(3)(PO(3)H)(2)(PO(3))}(H2O)]ClO4.3H2O (4), [Ln = Gd (4
      Gd), Tb (4 Tb)]. Compounds within each type are isostructural. In compounds 1,
      dimers of {Ln2(notpH4)2(NO3)2(H2O)2} are found, in which the two lanthanide atoms
      are connected by two pairs of O-P-O and one pair of mu-O bridges. The NO3- ion
      serves as a bidentate terminal ligand. Compounds 2 contain similar dimeric units
      of {Ln2(notpH4)2(H2O)2} that are further connected by a pair of O-P-O bridges
      into an alternating chain. The Cl- ions are involved in the interchain hydrogen
      bonding networks. A similar chain structure is also found in compounds 3; in this
      case, however, the chains are linked by ClO4- counterions through hydrogen
      bonding interactions, forming an undulating layer in the (011) plane. These
      layers are fused through hydrogen-bonding interactions, leading to a three
      dimensional supramolecular network with large channels in the [100] direction.
      Compounds 4 show an interesting brick-wall-like layer structure in which the
      neighboring lanthanide atoms are connected by a pair of O-P-O bridges. The ClO4-
      counterions and the lattice water molecules are between the layers. In all
      compounds the triazamacrocyclic nitrogen atoms are not coordinated to the Ln(III)
      ions. The anions and the pH are believed to play key roles in directing the
      formation of a particular structure. The fluorescence spectroscopic properties of
      the Eu and Tb compounds, magnetic properties of the Gd compounds, and the
      catalytic properties of 4 Gd were also studied.

PMID- 17171733
TI  - Studies of a cobalt(III) complex of the MMP inhibitor marimastat: a potential
      hypoxia-activated prodrug.
AB  - We report a potential means of selectively delivering matrix metalloproteinase
      (MMP) inhibitors to target tumour sites by use of a bioreductively activated
      Co(III) carrier system. The carrier, comprising a Co(III) complex of the tripodal
      ligand tris(methylpyridyl)amine (tpa), was investigated with the antimetastatic
      MMP inhibitor marimastat (mmstH(2)). The X-ray crystal structure of
      [Co(mmst)(tpa)]ClO(4) x 4H(2)O was determined and two-dimensional NMR revealed
      the existence of two isomeric forms of the complex in solution. Electrochemical
      analysis showed that the reduction potential of the complex is suitable for it to
      be bioreductively activated at hypoxic tumour sites. In vitro assays confirmed
      the stability of the prodrug in solution prior to reduction and revealed very low
      cytotoxicity against A2780 cells. In vivo testing in mice showed a higher level
      of tumour-growth inhibition by the complex than by free marimastat. Both free
      marimastat and and its Co(III) complex increased metastasis in the model used,
      with the complex significantly more active.

PMID- 17171734
TI  - Hydrogencyanamide-bridged one-dimensional polymers built on Mn(III)-Schiff base
      fragments: synthesis, structure, and magnetism.
AB  - The ability of NCNH(-) to construct transition metal coordination polymers and to
      transmit magnetic coupling was investigated. By introduction of various
      tetradentate Schiff base ligands (L) and different solvents (S), nine NCNH(-)
      bridged manganese(III) coordination complexes were obtained. Their structures can
      be divided into three types: I) NCNH-bridged chains built on mononuclear
      [Mn(III)(L)] units, [Mn(III)(L)(mu(1,3)-NCNH)](n) (L=5-Brsalen (1), 5-Clsalen
      (2)); II) NCNH-bridged chains built on dinuclear [Mn(III) (2)(L)(2)] units,
      complexes 3-8, [Mn(III) (2)(L)(2)(mu(1,3)-NCNH)]ClO(4)S (L=salen, 5-Fsalen, 5
      Clsalen, 5-OCH(3)salen; S=CH(3)OH or C(2)H(5)OH); III) NCNH-bridged Mn(III)
      dimers linked by hydrogen bonds into a 1D polymer, {[Mn(III)(3
      OCH(3)salen)(H(2)O)](2)(mu(1,3)-NCNH)}ClO(4) x 0.5 H(2)O (9, salen=N,N'
      bis(salicylidene)-1,2-diaminoethane). In these complexes, the N[triple chemical
      bond]C--NH(-) resonance structure dominates the bonding mode of the NCNH(-)
      ligand adopting the mu(1,3)-bridging mode. Magnetic characterization shows that
      the asymmetric NCNH(-) bridge transmits antiferromagnetic interaction between
      Mn(III) ions and often favors the weak ferromagnetism caused by spin canting in
      these one-dimensional chains. However, these complexes exhibit different magnetic
      behaviors at low temperatures.

PMID- 17171735
TI  - Bifunctional polymeric organocatalysts and their application in the cooperative
      catalysis of Morita-Baylis-Hillman reactions.
AB  - A series of soluble, non-cross-linked polystyrene-supported triphenylphosphane
      and 4-dimethylaminopyridine reagents were prepared. Some of these polymeric
      reagents contained either alkyl alcohol or phenol groups on the polymer backbone.
      The use of these materials as organocatalysts in a range of Morita-Baylis-Hillman
      reactions indicated that hydroxyl groups could participate in the reactions and
      accelerate product formation. In the cases examined, phenol groups were more
      effective than alkyl alcohol groups for catalyzing the reactions. This article is
      one of the first reports of the synthesis and use of non-natural, bifunctional
      polymeric reagents for use in organic synthesis in which both functional groups
      can cooperatively participate in the catalysis of reactions.

PMID- 17171736
TI  - Sandwich-like compounds based on the all-metal aromatic unit Al(4)2- and the main
      group metals M (M=Li, Na, K, Be, Mg, Ca).
AB  - Inspired by the pioneering experimental characterisation of the all-metal
      aromatic unit Al(4)2- in the bimetallic molecules MAl4- (M=Li, Na, Cu) and by the
      very recent theoretical design of sandwich-type transition-metal complexes
      [Al4MAl4]q- (q=0-2; M=Ti, V, Cr, Zr, Nb, Mo, Hf, Ta, W), we used density
      functional theory (DFT) calculations (B3LYP/6-311+G(d) to design a series of
      novel non-transition-metal sandwich complexes based on the all-metal aromatic
      unit Al4(2-) and the main-group metals M (M=Li, Na, K, Be, Mg, Ca). The
      traditional homo-decked sandwich compounds [Al4MAl4]q- (without counterions) and
      (nM)q+[Al4MAl4]q- (with counterions M) (q=2-3, M=Li, Na, K, Be, Mg, Ca), although
      some of them are truly energy minima, have a much higher energy than many fused
      isomers. We thus concluded that it seems unlikely for Al4(2-) to sandwich the
      main-group metal atoms in the homo-decked sandwich form. Alternatively, we
      proposed a new type of sandwich complex, namely hetero-decked sandwich compounds
      [CpMAl4]q-, that are the ground-state structures for each M both with and without
      counterions. It was shown that with the rigid Cp- partner, the all-metal aromatic
      unit Al(4)2- might indeed act as a "superatom". These new types of all-metal
      aromatic unit-based sandwich complexes await future experimental verification.

PMID- 17171737
TI  - Enantioselective synthesis of natural polyoxygenated cyclohexanes and
      cyclohexenes from [(p-tolylsulfinyl)methyl]-p-quinols.
AB  - Exploitation of the beta-hydroxysulfoxide fragment present in a number of
      enantiomerically pure (SR)- and (SS)-[(p-tolylsulfinyl)methyl]-p-quinols allowed
      chemo- and stereocontrolled conjugate additions of different organoaluminium
      reagents to the cyclohexadienone moiety. The same fragment was also shown to act
      as an efficient chiral masking carbonyl group, after oxidation to sulfone and
      retroaddition in basic medium, with elimination of methyl p-tolyl sulfone.
      Through the use of both transformations as key steps, enantiocontrolled syntheses
      of different natural products-such as the two enantiomers of dihydroepiepoformin,
      (-)-gabosine O, (+)-epiepoformin, (-)-theobroxide and (+)-4-epigabosine A (an
      epimer of the natural product gabosine A)-has been achieved. The presence of the
      beta-hydroxy sulfone moiety makes the cyclic structures rigid, allowing a number
      of stereoselective transformations such as carbonyl reductions, enone
      epoxidations or cis-dihydroxylations, en route to the natural structures. The
      observed selectivities were dependent on the particular substitution in each
      substrate, providing evidence of a strong influence of remote groups on the
      preferred approach of the reactants to the reactive conformations. An advanced
      precursor of natural (+)-harveynone was also synthesized, but the isolation of
      the natural product was not possible because of the instability of the
      corresponding enone, containing a triple bond, under the basic conditions
      necessary to eliminate the beta-hydroxy sulfone. This demonstrated that the
      limitations of the use of the beta-hydroxy sulfoxide as a chiral protecting
      carbonyl group were dependent on the relative stabilities of the final targets in
      the presence of the required base.

PMID- 17171738
TI  - Osmium-mediated C--H and C--C bond cleavage of a phenolic substrate: p-quinone
      methide and methylene arenium pincer complexes.
AB  - The diphosphine 2,4,6-(CH(3))(3)-3,5-(iPr(2)PCH(2))(2)C(6)OH (1) reacts with
      [OsCl(2)(PPh(3))(3)] in presence of an excess of triethylamine to yield the
      isomeric para-quinone methide derivatives [Os{4-(CH(2))-1-(O)-2,6-(CH(3))(2)-3,5
      (iPr(2)PCH(2))(2)C(6)}(Cl)(H)(PPh(3))] (2 and 3), which differ in the positions
      of the mutually trans hydride and chloride ligands. Complex 2 reacts with CO to
      afford the dicarbonyl species [Os{1-(O)-2,4,6-(CH(3))(3)-3,5
      (iPr(2)PCH(2))(2)C(6)}(Cl)(CO)(2)] (4), which results from hydride insertion into
      the quinonic double bond. Protonation of 2 and 3 leads to the formation of the
      methylene arenium derivative [Os{4-(CH(2))-1-(OH)-2,6-(CH(3))(2)-3,5
      (iPr(2)PCH(2))(2)C(6)}(Cl)(H)(PPh(3))][OSO(2)CF(3)] (5 a). The diphosphine 1
      reacts with [OsCl(2)(PPh(3))(3)] at 100 degrees C under H(2) to afford [Os{1-(OH)
      2,6-(CH(3))(2)-3,5-(iPr(2)PCH(2))(2)C(6)}(Cl)(H(2))(PPh(3))] (6), a PCP pincer
      complex resulting formally from C(sp(2))--C(sp(3)) cleavage of the C--CH(3) group
      in 1. C--C hydrogenolysis resulting in the same complex is achieved by heating 2
      under H(2) pressure. Reaction of the diphosphine substrate with
      [OsCl(2)(PPh(3))(3)] under H(2) at lower temperature allows the observation of a
      methylene arenium derivative resulting from C--H activation, [Os{4-(CH(2))-1-(OH)
      2,6-(CH(3))(2)-3,5-(iPr(2)PCH(2))(2)C(6)}(Cl)(2)(H)] (7). This compound reacts
      with PPh(3) in toluene to afford the ionic derivative [Os{4-(CH(2))-1-(OH)-2,6
      (CH(3))(2)-3,5-(iPr(2)PCH(2))(2)C(6)}(Cl)(H)(PPh(3))]Cl (5 b). X-ray diffraction
      studies have been carried out on compounds 2, 3, 4, 5 b, 6, and 7, which allows
      the study of the structural variations when going from methylene arenium to
      quinone methide derivatives.

PMID- 17171739
TI  - Fischer carbene complexes: beautiful playgrounds to study single electron
      transfer (SET) reactions.
AB  - The knowledge of the reactivity of Fischer carbene complexes in electron transfer
      processes is still in the early stage of development, but interesting advances
      are foreseeable in this young branch of metal-carbene chemistry. Although these
      compounds have a dual reactivity (which makes them good substrates for oxidation
      and reduction processes), their behavior towards chemical electron transfer (ET)
      reagents was unknown until very recently. This article covers the progress
      accomplished in the reactivity of these compounds towards chemical ET reagents
      (C(8)K or SmI(2)), as well as the use of nonconventional sources of electrons,
      such as electrospray ionization (ESI) to induce ET processes. Special emphasis
      will be made on the effect of the structure of the starting carbene in the
      outcome of the reaction and in discussing the different mechanisms proposed.

PMID- 17171740
TI  - Chelating dialkoxide titanium complex: a versatile building block for the
      construction of heterometallic derivatives.
AB  - The heterometallic complex [TiCp*(O(2)Bz)(2)AlMe(2)] (2) has been synthesised by
      reaction of [TiCp*(O(2)Bz)(OBzOH)] (1) with AlMe(3) (Cp*=eta(5)-C(5)Me(5);
      Bz=benzyl). Complex 1 reacts with HOTf to yield the cationic derivative
      [TiCp*(OBzOH)(2)]OTf (3) (HOTf=HSO(3)CF(3)). Compound 3 reacts with [{M(mu
      OH)(cod)}(2)] (M=Rh, Ir; cod=cyclooctadiene) to render the early-late
      heterometallic complexes [TiCp*(O(2)Bz)(2){M(cod)}(2)]OTf (M=Rh (4); Ir (5)). The
      molecular structure of complex 4 has been established by single-crystal X-ray
      diffraction studies.

PMID- 17171741
TI  - Economic cost of dementia patients according to the limitation of the activities
      of daily living in Korea.
AB  - BACKGROUND: Dementia is expected to become a significant social burden in the
      future. However, there are few reports that have estimated the total economic
      cost of dementia, particularly according to the limitation in the activities of
      daily living (ADL) in Korea. OBJECTIVES: This study is to analyze the health care
      expenditures and cost per dementia patient, and estimated the total economic cost
      of dementia. METHODS: Caregivers of 609 dementia patients, who were randomly
      selected from a nationwide claim database of the Korean National Health Insurance
      Corporation, were interviewed using structured questionnaire in the period of
      September 2005. The total cost including the direct and indirect costs during a
      year was calculated. The patients were stratified into three limitation groups
      according to their ADL score. The cost according to the three limitation groups
      was analyzed. The national cost of dementia patients was then estimated. RESULTS:
      The total cost per dementia patient in Korea was $7,462. The direct and indirect
      costs were $6,626 and $836 per patient, respectively. The cost increased with
      increasing degree of limitation in the patient's ADL. Over a 1-year period, the
      total cost per patient in the low limitation group was lower ($3,698) than that
      of the moderate ($6,064) and high ($11,428) limitation group. CONCLUSIONS: This
      study demonstrates that the direct and indirect costs of dementia are
      considerately small for patients with lower limitation in their ADL. The total
      economic cost of dementia per year was estimated to be in the range of 1.3 to 3.3
      billion dollars on assumptions in Korea.

PMID- 17171742
TI  - Formation of gels and liquid crystals induced by PtPt and pi-pi* interactions in
      luminescent sigma-alkynyl platinum(II) terpyridine complexes.

PMID- 17171743
TI  - Nitrogen-carbon bond formation from N2 and CO2 promoted by a hafnocene dinitrogen
      complex yields a substituted hydrazine.

PMID- 17171744
TI  - Self-assembly of organocatalysts: fine-tuning organocatalytic reactions.

PMID- 17171745
TI  - Does Cob(II)alamin act as a conductor in coenzyme B12 dependent mutases?

PMID- 17171746
TI  - Stable mononuclear lead(III) compound: a lead-centered radical.

PMID- 17171747
TI  - Chiral dendralenes for rapid access to enantiomerically pure polycycles.

PMID- 17171748
TI  - Dynamic combinatorial resolution: direct asymmetric lipase-mediated screening of
      a dynamic nitroaldol library.

PMID- 17171749
TI  - Strategies for the synthesis of fusicoccanes by Nazarov reactions of
      dolabelladienones: total synthesis of (+)-fusicoauritone.

PMID- 17171750
TI  - Evaluation of the home help service and its impact on the informal caregiver's
      burden of dependent elders.
AB  - AIM: This study looks at the objective and subjective characteristics of home
      respite service provision and its impact on the informal care burden of dependent
      elders. METHOD: A sample of 296 dependent people and their informal caregivers
      was randomly selected among users and non-users of the Home Help Service (HHS) in
      an autonomous Spanish region (Comunidad Valenciana). An experimental design was
      used and a field study was carrying out that collected information on
      sociodemographic variables of the dependent person and his/her caregiver, HHS
      characteristics and the assessment of the services delivered by this resource as
      well as the informal caregivers'burden. RESULTS: The results show that the
      services of this resource are very limited, with low cover and frequency, and
      they do not address the real dependency needs in specific activities of daily
      living. However, users and caregivers are satisfied with this care and experience
      a higher quality of life since it was implemented, although the HHS does not
      alleviate informal caregivers' stress. CONCLUSION: These data show the need to
      extend the services delivered by the HHS and the duration of care, address the
      caregiver's need for psychological care, and look at potentially modifiable
      variables in the care context when designing prevention and psychosocial
      intervention programmes to lessen the informal caregiver's burden.

PMID- 17171751
TI  - Correlation between actigraphy and nurses' observation of activity in dementia.

PMID- 17171752
TI  - Frontal lobes and older sex offenders: a preliminary investigation.

PMID- 17171754
TI  - Development of CD25- regulatory T cells following heart transplantation: evidence
      for transfer of long-term survival.
AB  - Donor-specific heart allograft acceptance can be induced in the MHC-mismatched
      LEW.1 W to LEW.1A rat by donor-specific transfusions. Whereas the induction phase
      of tolerance has been studied in detail, its maintenance remained poorly
      understood. Here, we performed a side-by-side comparison of CD25+ and CD25-
      splenic T cells of 100-day tolerant rats. Administration of CD25- T cells from
      tolerant rats to sublethally irradiated recipients transferred long-term graft
      survival. These CD25- T cells displayed a decreased donor-specific response in
      the mixed lymphocyte reaction and presented suppressive activity. These CD25- T
      cells accumulated IFN-gamma, IL-10 and Foxp3 transcripts. The in vitro
      suppressive activity of CD25- T cells required both cell contact and soluble
      factors (IL-10 and IFN-gamma). The CD25+ T cells from tolerant rats did not show
      any modification of their regulatory properties. We show that splenic CD25- T
      cells of tolerant rats contribute to the maintenance of tolerance following the
      transplantation. Our data show that regulatory T cells are not restricted to the
      CD4+ CD25+ T cell subset and provide new insights on the mechanisms of tolerance
      to allograft following donor cell priming.

PMID- 17171755
TI  - Functional expression of chemokine receptor CCR6 on human effector memory CD8+ T
      cells.
AB  - Since CCR6 is a receptor for the chemokine CCL20, which is produced in tissues
      such as intestine and colon, it is thought that T cells expressing CCR6 are
      involved in mucosal immunity. The expression and function of CCR6 on human CD8+ T
      cells have not well been analyzed, although it is known that this receptor is
      expressed on a subset of human CD8+ T cells. We here characterize human CCR6+
      CD8+ T cells. Multi-color flow cytometric analysis demonstrated that CCR6+ cells
      are predominantly found among CD8+ T cells having the memory phenotype. The
      expression of CCR6 is positively and negatively correlated with that of CCR5 and
      CCR7, respectively. CCR6+ CD8+ T cells express granzyme A and a low level of
      perforin but not granzyme B. In addition, a major population among these cells
      has the ability to produce IFN-gamma and TNF-alpha but not IL-2. These results
      indicate that CCR6+ CD8+ T cells have characteristics of early effector memory
      cells rather than effector or central memory cells. A chemotaxis assay revealed
      that CCR6+ CD8+ T cells have the ability to migrate in response to CCL20,
      suggesting that these T cells migrate to tissues such as colon and are involved
      in mucosal immunity.

PMID- 17171756
TI  - Terminal complement complex C5b-9-treated human monocyte-derived dendritic cells
      undergo maturation and induce Th1 polarization.
AB  - Sublytic C5b-9 has been described as a pro-inflammatory mediator that triggers
      cell activation rather than inducing cell death. Dendritic cells (DC) play a
      critical role in controlling antigen-specific immune responses. Although DC
      maturation induced by various stimuli has been well characterized, the role of
      C5b-9 in DC function has not been described. In this report, we use in vitro
      assembled functional C5b-9 based on purified distal complement protein to show
      that DC maturation is promoted by sublytic C5b-9. This was demonstrated by up
      regulation of CD83, HLA-antigens and costimulatory molecules, including CD80,
      D86, B7-H1, B7-H3, B7-H4 and BTLA. In addition, secretion of cytokines such as
      interleukin (IL)-12 and tumor necrosis factor-alpha was increased while the
      capacity for antigen uptake (FITC-Dextran and Lucifer Yellow) was reduced in C5b
      9-treated DC. Mixed lymphocyte reactions indicated that C5b-9-activated DC acted
      as stimulators that significantly promoted CD4+ T cell activation and elicited
      production of cytokines, including interferon-gamma and IL-2. Interestingly, C5b
      9-treated DC also orient CD4+ CD45RA+ naive T cells toward Th1 polarization. Our
      results are the first to report that DC are potential immunoregulatory targets of
      C5b-9, suggesting that C5b-9 bridges innate and acquired immunity by inducing DC
      maturation.

PMID- 17171757
TI  - Three common alleles of KIR2DL4 (CD158d) encode constitutively expressed,
      inducible and secreted receptors in NK cells.
AB  - Genetic polymorphism of KIR2DL4 results in alleles with either 9 or 10
      consecutive adenines in exon 6, which encodes the transmembrane domain. "10A"
      alleles encode a membrane-expressed receptor that is constitutively expressed on
      resting CD56bright NK cells and on CD56dim cells after culture. However, in some
      individuals with the 10A allele, KIR2DL4 cannot be detected on their resting
      CD56bright NK cells. "9A" alleles have been predicted to encode a secreted
      receptor due to the splicing out of the transmembrane region. In this
      publication, we show that those individuals with a 10A allele who lack detectable
      KIR2DL4 on CD56bright NK cells express a KIR2DL4 receptor in which the D0-domain
      is excised. This Delta-D0 receptor cannot be detected by the available anti
      KIR2DL4 monoclonal antibodies. In such individuals, KIR2DL4 becomes detectable on
      cultured NK cells due to up-regulation of the full-length KIR2DL4 transcript. In
      all individuals with 10A alleles, KIR2DL4 ceases to be expressed at the cell
      surface 16 days after activation, despite the maintenance of maximal levels of
      KIR2DL4 mRNA transcription, suggesting the existence of a negative regulator of
      cell surface expression. Finally, we show that the 9A allele can produce a
      secreted KIR2DL4 receptor.

PMID- 17171758
TI  - Helper function of cytolytic lymphocytes: switching roles in the immune response.
AB  - T helper (Th) cells and cytolytic T lymphocytes (CTL) play defined roles in the
      cellular immune response. This distinction wavered when Th lymphocytes were shown
      to kill antigen-presenting cells displaying the relevant antigen. Here we
      demonstrate that also the opposite can be true: CTL can exert helper functions.
      We noticed that certain CMV-specific CTL lines grew after antigen activation also
      without exogenous IL-2. These lines produced their own IL-2, which supported the
      expansion of other CTL and Th cell lines. High levels of helper cytokines like IL
      4, IL-5 and IL-6 were detected in the culture supernatants. Thus, we set up a
      helper assay to study the functional interactions between T cells (or their
      supernatants) and B cells. Conditioned media from helper CTL lines induced
      secretion of antigen-specific antibodies by B cells pulsed with antigen as first
      signal. We conclude that it is possible to isolate CTL lines that exhibit helper
      functions for T cells and B cells. If this possibility is proven also in vivo, we
      should revise some of our views on the pathogenesis of diseases in which CD8
      cells are key players, such as in viral infections, graft rejection and GVHD.

PMID- 17171759
TI  - Modulation of 2B4 (CD244) activity and regulated SAP expression in human NK
      cells.
AB  - The adapter protein SAP is important for the signal transduction of the family of
      SLAM-related receptors (SRR), which have important immune-modulating functions.
      The importance of SAP and SRR for a functional immune reaction becomes obvious in
      patients suffering from X-linked lymphoproliferative disease, which is
      characterized by non-functional SAP. Here we investigate the regulation of SAP
      expression in human NK cells. We demonstrate that SAP mRNA expression and protein
      levels are low in freshly isolated resting NK cells. IL-2 stimulation leads to an
      up-regulation of SAP expression, which can be enhanced by IL-12, the stimulation
      of TLR3 by polyinosinic-polycytidylic acid (poly(I:C))and to a lesser extent by
      IFN-alpha. EAT-2, a SAP-related adapter protein, is already detectable in resting
      NK cells and does not change its expression after IL-2 stimulation. The
      regulation of SAP has functional consequences for the stimulation of NK cell
      cytotoxicity by 2B4. In resting NK cells, 2B4 stimulation can only enhance NK
      cell lysis when co-triggered with other activating NK cell receptors. In IL-2
      activated NK cells with high SAP expression the triggering of 2B4 alone is
      sufficient to induce NK cell cytotoxicity, demonstrating a correlation between
      the regulated SAP expression and the function of 2B4.

PMID- 17171760
TI  - The germinal center response is impaired in the absence of T cell-expressed
      CXCR5.
AB  - Germinal centers support the differentiation of memory B cells and long-lived
      antibody-secreting cells during infection or upon vaccination. Here, we
      constructed mice with T cells that selectively lack the chemokine receptor CXCR5
      to determine if expression of this receptor by T cells is mandatory for germinal
      center formation and function. In these animals, germinal centers that are
      properly localized in B cell follicles and contain T cells do form after
      immunization with a thymus-dependent antigen. However, fewer and smaller germinal
      centers form, resulting in a significant reduction in the frequency of germinal
      center B cells. The defect in germinal center formation is paralleled by
      decreased frequencies of isotype-switched antibody-secreting cells in the spleen
      and bone marrow and reduced serum concentrations of total and high-affinity
      hapten-specific IgG1. The results demonstrate that although CXCR5-dependent T
      cell positioning is important for maximal induction and expansion of germinal
      centers, stimulation of isotype class switching, and development of antibody
      secreting cells that seed the spleen and bone marrow, it is not absolutely
      required for the formation and function of follicular germinal centers.

PMID- 17171761
TI  - Faithful activation of an extra-bright red fluorescent protein in "knock-in" Cre
      reporter mice ideally suited for lineage tracing studies.
AB  - The considerable potential of Cre recombinase as a tool for in vivo fate-mapping
      studies depends on the availability of reliable reporter mice. By targeting a
      tandem-dimer red fluorescent protein (tdRFP) with advanced spectral and
      biological properties into the ubiquitously expressed ROSA26 locus of C57BL/6-ES
      cells, we have generated a novel inbred Cre-reporter mouse with several unique
      characteristics. We directly demonstrate the usefulness of our reporter strain in
      inter-crosses with a "universal Cre-deleter" strain and with mice expressing Cre
      recombinase in a T lineage-specific manner. Cytofluorometric and histological
      analyses illustrate: (i) non-toxicity and extraordinary brightness of the
      fluorescent reporter, allowing quantitative detection and purification of labeled
      cells with highest accuracy, (ii) reliable Cre-mediated activation of tdRFP from
      an antisense orientation relative to ROSA26 transcription, effectively excluding
      "leaky" reporter expression, (iii) absence of gene expression variegation
      effects, (iv) quantitative detection of tdRFP-expressing cells even in
      paraformaldehyde-fixed tissue sections, and (v) full compatibility with GFP/YFP
      based fluorescent markers in multicolor experiments. Taken together, the data
      show that our C57BL/6-inbred reporter mice are ideally suited for sophisticated
      lineage-tracing experiments requiring sensitive and quantitative
      detection/purification of live Cre-expressing cells and their progeny.

PMID- 17171762
TI  - To switch or not to switch--the opposing roles of TACI in terminal B cell
      differentiation.
AB  - The TNF superfamily ligands BAFF and APRIL and their three receptors BAFFR, BCMA,
      and TACI comprise a network that is critically involved in the development and
      function of humoral immunity. Failure of this complex system is associated with
      autoimmune disease, B lymphocyte tumours, and antibody deficiency. While
      BAFF:BAFFR interactions control peripheral B cell survival and homeostasis, BCMA
      function seems limited to the survival of long-lived bone marrow plasma cells.
      The functional activity of the third receptor TACI is, however, ambiguous: while
      TACI-/- mice predominantly develop autoimmunity and lymphoproliferation, TACI
      deficiency in humans primarily manifests itself as an antibody deficiency
      syndrome. An article in this issue of the European Journal of Immunology
      demonstrates a negative regulation via TACI in human B cells by using TACI
      specific antibodies. B cell proliferation, class switch recombination, and Ig
      production induced by various stimuli were inhibited via TACI. Within the
      BAFF/APRIL network, the expression of the receptors and ligands is spatially, as
      well as temporally, highly regulated at various stages of B cell development and
      function. Defining the exact contribution of TACI stimulation by specific
      triggers in vitro enables us to better understand the complex, context-dependent
      responses initiated by TACI in vivo.

PMID- 17171763
TI  - Suicide-related behavior after psychiatric hospital discharge: Implications for
      risk assessment and management.
AB  - Suicide-related behavior (SRB), including suicide attempts and instrumental SRB,
      occurs far more often than completed suicide and exacts a toll on patients, their
      loved ones, and society. Nevertheless, few prospective studies of SRB have been
      conducted. In this study, 954 patients were interviewed in a psychiatric hospital
      and then followed for one year after discharge. During this one-year period,
      nearly one-quarter of patients (23%) engaged in SRB, with the rate of suicide
      attempts (18%) three times greater than the rate of instrumental SRB (5%). Risk
      factors for SRB were demographic (White ethnicity, female gender), clinical (past
      SRB, depression, impaired functioning), and contextual (unemployment, large
      social networks). In contrast with other studies, there was no "peak" in the risk
      of SRB shortly after hospital discharge. Instead, patients' rate of SRB was
      relatively constant over the one-year follow-up. Implications for risk assessment
      and management in acute inpatient settings are discussed.

PMID- 17171764
TI  - Short-Term Assessment of Risk and Treatability (START): The case for a new
      structured professional judgment scheme.
AB  - The Short-Term Assessment of Risk and Treatability (START) is a new structured
      professional judgment scheme intended to inform multiple risk domains relevant to
      everyday psychiatric clinical practice (e.g. risk to others, suicide, self-harm,
      self-neglect, substance abuse, unauthorized leave, and victimization). The
      article describes the processes involved in establishing an interdisciplinary
      approach to risk assessment and management. The authors present a review of the
      rationale for START, including the value of dynamic variables, the importance of
      strengths, and the extent to which clinicians must be attentive to multiple risk
      domains, reflecting theoretical and scientific evidence of the overlap among
      risks. Using the development, validation, and implementation of START as an
      example, the authors describe the processes by which other researchers,
      clinicians, and administrators could adapt existing assessment schemes or create
      new ones to bridge some remaining gaps in the risk assessment and management
      continuum.

PMID- 17171765
TI  - A dynamic assessment of offender risk, needs, and strengths in a sample of pre
      release general offenders.
AB  - Static, dynamic, and protective factors have been identified as three focal
      domains significantly related to offender recidivism. However, few measures
      include comprehensive and inclusive assessment of these variables. The Inventory
      of Offender Risk, Needs, and Strengths (IORNS) was developed to fill a void in
      the assessment of risk and needs for offenders. The current study examines the
      reliability and initial validity of the IORNS in a sample of pre-release
      offenders assessed for risk and treatment need. Results indicate moderate to high
      levels of internal consistency and identical IORNS scale results across race, and
      that the IORNS indexes, scales, and subscales display good convergent validity
      with self-report and interview measures of static risk, dynamic risk, antisocial
      behavior, psychopathy, personality pathology, substance abuse, depression, and
      anxiety. Initial predictive validity examination of the IORNS indicates that
      several of the indexes, scales, and subscales were able to differentiate
      offenders who were sent back to prison for half-way house rule violations from
      those who did not violate rules.

PMID- 17171766
TI  - Evaluating the validity of anger regulation problems, interpersonal style, and
      disturbed mental state for predicting inpatient violence.
AB  - Research has been conducted to try to identify risk factors to help predict which
      patients will be violent during psychiatric hospitalization. Despite the
      relatively large amount of research conducted, it is difficult to draw any firm
      conclusions, as the studies vary considerably in study design, methods used, and
      choice of outcome measures. Studies also tend to focus on risk prediction, even
      though risk management is the primary aim of clinical practice in mental health
      services and few studies have focused on a theoretical basis for understanding
      violence. This study assessed the predictive validity of brief assessment scales
      in a sample of 94 forensic inpatients who had been inpatient for a median of 521
      days, to test the hypotheses that anger regulation problems, interpersonal style,
      and disturbed mental state would be linked to increased violence risk in a
      forensic hospital during a hospital stay. The outcome variables for this study
      were physical violence against another and/or clear threats of physical violence.
      The results of this study provide support for the hypotheses, and this remained
      the case after controlling for age, gender, length of stay, and presence of major
      mental disorder. The findings should not only assist clinicians with assessment
      and management of risk but also support the reconceptualizing of risk prediction
      research to reflect the task of clinical risk management.

PMID- 17171767
TI  - Outcome of patients rehabilitated through a New Zealand forensic psychiatry
      service: A 7.5 year retrospective study.
AB  - This paper describes a 7.5 year retrospective study of all patients discharged
      from inpatient forensic services to forensic community team (FCT) follow-up from
      the Auckland Regional Forensic Psychiatry Service. Patients' files were studied
      for clinical, criminal, and risk data, type of service delivered, and final level
      of function achieved in the community. Rearrest, re-hospitalization, and
      reimprisonment data were obtained from clinical, court, and prison records.105
      patients were included. The most common diagnosis was a psychotic disorder, and
      index offending behaviour was typically violent. The median period of inpatient
      stay was 36 months and mean subsequent FCT follow-up 21.7 months (SD 17.8). The
      majority of patients were from Maori and Pacific Island ethnic groups. At the end
      of the study, half were in independent living, half were in some form of
      employment, and 19% were readmitted to a forensic hospital. One patient was
      rearrested but not reimprisoned whilst under forensic community team care.
      However, 9 of the 48 who were discharged to general mental health services were
      rearrested and 5 reimprisoned. Only two offences were as serious as the original
      index offence. Broad based assertive, mandated, and committed forensic
      rehabilitation can achieve high quality outcomes. These levels of function may
      not be sustained under less assertive care.

PMID- 17171769
TI  - The classification of violence risk.
AB  - The Classification of Violence Risk (COVR) is an interactive software program
      designed to estimate the risk that a person hospitalized for mental disorder will
      be violent to others. The software leads the evaluator through a chart review and
      a brief interview with the patient. At the end of this interview, the software
      generates a report that contains a statistically valid estimate of the patient's
      violence risk-ranging from a 1% to a 76% likelihood of violence-including the
      confidence interval for that estimate, and a list of the risk factors that the
      program took into account to produce the estimate. In this article, the
      development of the COVR software is described and several issues that arise in
      its administration are discussed.

PMID- 17171770
TI  - The dynamic appraisal of situational aggression: an instrument to assess risk for
      imminent aggression in psychiatric inpatients.
AB  - Considerable research has attempted to delineate the demographic and clinical
      characteristics of high-risk psychiatric patients and identify salient modifiable
      aspects of aggression prone environments. Recently, there has also been increased
      interest in the development and testing of structured schemes for the assessment
      of risk for aggression within inpatient psychiatric settings. Although some of
      these methods show acceptable predictive validity, their ability to inform day-to
      day treatment and management decisions is limited. The current research was
      designed to identify existing and novel risk factors that would assist staff to
      identify and manage the risk for aggression in psychiatric inpatient populations.
      Results showed that assessments supported by structured risk measures were more
      accurate than unaided clinical judgements based only on nurses' clinical
      experience and knowledge of the patient alone. Seven test items emerged that were
      maximally effective at identifying acute psychiatric patients at risk for
      engaging in inpatient violence within 24 hours; these items have been combined in
      the development of the Dynamic Appraisal of Situational Aggression. Empirical
      analyses and clinical experience support the efficacy of the instrument in
      assisting clinical staff in the identification and management of inpatient
      aggression.

PMID- 17171771
TI  - Public attitudes about the culpability and punishment of young offenders.
AB  - Opinions of 789 community adults were individually assessed, using a video-clip
      of an actual armed robbery and other measures, to determine whether attitudes
      toward the culpability and appropriate punishment of young offenders were linked
      to offenders' age, race, and physical appearance. Three major findings emerged:
      (1) community adults endorse the view that criminal choices of young offenders
      are influenced by their developmental immaturity and attribute more
      responsibility for the criminal act as the actor gets older; (2) the public has a
      relatively strong preference for differential treatment of juvenile and adult
      offenders; and (3) attitudes about culpability and punishment are not influenced
      by the culprit's race, physical maturity, or appearance of "toughness."
      Indications that punitive public opinion toward youth crime may be changing and
      implications for juvenile justice policy of the study's findings are discussed.

PMID- 17171772
TI  - Pre-arrest diversion of people with mental illness: Literature review and
      international survey.
AB  - Mental health diversion is a process where alternatives to criminal sanctions are
      made available to persons with mental illness (PMI) who have come into contact
      with the law. One form of mental health diversion is pre-arrest, in which the
      police use their discretion in laying charges. Concomitant with the growth of pre
      arrest diversion programs is a growing body of research devoted to the
      phenomenon. The purpose of this paper is to review the existing literature of pre
      arrest diversion, and to report the results of an international survey of pre
      arrest diversion programs we conducted to identify evidence-based practices. On
      the basis of our review and survey, we note that successful pre-trial programs
      appear to integrate relevant mental health, substance abuse and criminal justice
      agencies by having regular meetings between key personnel from the various
      agencies. Often, a liaison person with a mandate to effect strong leadership
      plays a key role in the coordination of various agencies. Streamlining services
      through the creation of an emergency drop-off center with a no-refusal policy for
      police cases is seen as crucial. While there is some indication that mentally ill
      offenders benefit from their participation in this form of diversion, the
      evaluative literature has not yet achieved the "critical mass" necessary to
      create generalizable, evidence-based knowledge. The absence of generally agreed
      upon outcomes could lead to the inequitable application of basic principles of
      diversion. We suggest that indicators, benchmarks, and outcomes must be agreed
      upon if a comprehensive understanding of pre-arrest programs is to emerge.

PMID- 17171773
TI  - Mass spectrometry and scanning electron microscopy study of silicone tunneled
      dialysis catheter integrity after an exposure of 15 days to 60% ethanol solution.
AB  - Anti-infectious lock is an emerging therapeutic option for preventing and/or
      controlling catheter-associated infection. Ethanol has widespread bactericidal
      activity, limited side effects, and low risk of inducing antimicrobial
      resistance. However, concerns have been raised about ethanol-induced catheter
      structural degradation. In this study, silicone catheters were immersed at 37
      degrees C in three different solvents: 0.9% sodium chloride, 60% ethanol, and 95%
      ethanol for 4 h, 15 days and 15 days after a first storage of 4 h. Scanning
      electron microscopy (magnification 1000-20 000 times) of the inner surface of the
      catheter revealed no damage to the lumen surfaces of catheters immersed in 95%
      ethanol for 15 days compared with the reference catheter. Gas chromatography/mass
      spectrometry (GC/MS) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOFMS) analysis of the storage solutions revealed
      a significant release of polydimethylsiloxanes having a number of
      dimethylsiloxane units lower than 30 in the 95% ethanol solution and a structure
      highly consistent with a cyclic structure. Most release occurred within the first
      4 h of exposure. In contrast, there was no difference in the small amounts of
      silicone released in 0.9% sodium chloride as reference and 60% ethanol solution,
      whatever the exposure time. These results should allow the development of
      clinical trials to assess the efficacy of the 60% ethanol lock technique in
      preventing or controlling the infectious complications of silicone dialysis
      catheters.

PMID- 17171774
TI  - 2B or not 2B, that is the question: further investigations into the use of pencil
      as a matrix for matrix-assisted laser desorption/ionisation.
AB  - The effective use of pencil as a matrix for matrix-assisted laser
      desorption/ionisation (MALDI) for the study of actinides has previously been
      demonstrated (Black et al., Rapid Commun. Mass Spectrom. 2006; 20: 1053). Here,
      the scope of the types of molecules amenable to analysis by this method has been
      extended, establishing that approximately 90% of a library containing 50 diverse
      small molecules can be successfully analysed by this technique. Further, the role
      played by the bulk materials present in the different pencil leads has been
      investigated and a simple one-step deposition of matrix and calibration materials
      has been achieved through the fabrication of different calibration pencils (Cali
      Pens).

PMID- 17171775
TI  - Characterization and online detection of aromatic alkaloids in the ascidian
      Lissoclinum cf. badium by liquid chromatography/UV detection mass spectrometry.
AB  - A detection method based on high-performance liquid chromatography coupled with
      ultraviolet diode-array detection and electrospray ionization ion trap tandem
      mass spectrometry (HPLC-UV-ESI-MS/MS) was developed to investigate the total
      alkaloids prepared from the ascidian Lissoclinum cf. badium. The aromatic
      alkaloids possessing polysulfide structures are the major bioactive constituents
      isolated from ascidians of the genera Lissoclinum, Eudistoma, and Polycitor.
      These compounds presented various important biological activities. The ESI-MS
      fragmentation behavior of this kind of alkaloids was studied, and the
      fragmentation was characterized by elimination of the NH(CH(3))(2) moiety. The
      use of reversed-phase HPLC/UV-ESI-MS allowed the online separation and detection
      of 25 aromatic alkaloids. This approach provided data that can be used for
      detection of biologically active aromatic alkaloids from marine organisms.

PMID- 17171777
TI  - Determination of miglitol in human plasma by liquid chromatography/tandem mass
      spectrometry.
AB  - A rapid and sensitive method for the determination of miglitol in human plasma
      using voglibose as internal standard has been developed and validated. Samples of
      plasma were deproteinated with acetonitrile and washed with dichloromethane
      before being analyzed by reversed-phase high-performance liquid chromatography
      (HPLC). Separation was carried out on a short Nucleosil C(18) column (5 microm,
      50 x 4.6 mm i.d.) using 10 mmol/L ammonium acetate at 1.0 mL/min as mobile phase.
      The detector was an Applied Biosystems Sciex API 4000 mass spectrometer using
      atmospheric pressure chemical ionization (APCI) for ion production. The
      instrument was operated at unit resolution in the multiple reaction monitoring
      mode. The assay was linear over the range 5.00-2000 ng/mL with a limit of
      detection of 1.00 ng/mL. Intra- and inter-day precision were <2.82% and <2.92%,
      respectively, with accuracy of 93.3-106%. The assay was successfully applied to a
      clinical pharmacokinetic study of miglitol given as a single oral dose (50 mg) to
      healthy volunteers.

PMID- 17171776
TI  - A simple and rapid confirmatory assay for analyzing antibiotic residues of the
      macrolide class and lincomycin in bovine milk and yoghurt: hot water extraction
      followed by liquid chromatography/tandem mass spectrometry.
AB  - A rapid and simple sample preparation procedure for determining residues of
      antibiotics of the class of macrolides and lincomycin in whole milk and yoghurt
      by liquid chromatography/tandem mass spectrometry (LC/MS/MS) is presented. The
      method is based on the matrix solid-phase dispersion (MSPD) technique with hot
      water as extractant. After dispersing samples of milk and yoghurt on sand, target
      compounds were eluted from the MSPD column by passing through it 5 mL of water
      acidified with 30 mmol/L formic acid and heated at 70 degrees C. After pH
      adjustment and filtration, a volume of 200 microL of the aqueous extract was
      directly injected into the LC column. MS data acquisition was generally performed
      in the multiple reaction monitoring (MRM) mode, selecting two precursor ion to
      product ion transitions for each target compound. Hot water appeared to be an
      efficient extracting medium, since absolute recoveries of the analytes in milk
      and yoghurt were respectively 68-86% and 82-96%. The method proved to be robust
      as matrix effects, even though present, did not affect significantly the accuracy
      of the method, as evidenced by analyzing six different batches of both milk and
      yoghurt. Using roxithromycin (a macrolide antibiotic not used in veterinary
      medicine) as surrogate internal standard, the accuracy of the method at three
      different spike levels of the analytes in milk and yoghurt was 86-107% (RSDs not
      larger than 10%) and 97-117% (RSDs not larger than 13%), respectively. On the
      basis of a signal-to-noise ratio of 10, we estimated this method can quantify a
      few ppb of the analytes in milk and yoghurt. These concentrations are well below
      the tolerance levels of macrolides and lincomycin in milk set by both the
      European Union and the US Food and Drug Administration. On analyzing six yoghurt
      samples, we found evidence for the fact that one of the six samples was
      contaminated with erythromycin B.

PMID- 17171778
TI  - The distinction of underivatized monosaccharides using electrospray ionization
      ion trap mass spectrometry.
AB  - A convenient method for distinguishing underivatized isomeric monosaccharides has
      been established using electrospray ionization ion trap mass spectrometry (ESI
      ITMS). Mass spectra of hexoses (glucose, galactose, and mannose), N
      acetylhexosamines (N-acetylglucosamine, N-acetylgalactosamine, and N
      acetylmannosamine) and hexosamines (glucosamine, galactosamine, and mannosamine)
      dissolved in solvent containing 1 mM ammonium acetate were obtained in the
      positive ion mode. Glucose was distinguished from galactose and mannose in the
      MS(2) spectrum of the [M+NH(4)](+) ion at m/z 198. The MS(3) spectra generated
      from [M+NH(4)-H(2)O-NH(3)](+) at m/z 163 showed that galactose and mannose could
      be distinguished by the ratio of peak intensities at m/z 145 and 127, while the
      three N-acetylhexosamine and hexosamine stereochemical isomers could be
      identified by the relative abundance ratios of product ions observed in MS(3)
      spectra. The investigation of MS and MS(2) spectra from complexes of these
      monosaccharides with Na(+) and Pb(2+) failed to distinguish these monosaccharide
      isomers. Therefore, multiple stage mass analysis by ESI-ITMS using either
      [M+NH(4)](+) or [M+H](+) was useful to distinguish between the isomers of
      monosaccharides.

PMID- 17171779
TI  - The use of stable isotope ratio analyses to discriminate wild and farmed gilthead
      sea bream (Sparus aurata).
AB  - Continuous flow isotope ratio mass spectrometry (CF-IRMS) has been used to
      analyze samples of gilthead sea bream (g.s.b.) (Sparus aurata) of known
      geographical origin (four countries on the Mediterranean Sea) from wild and
      farmed sources (40 farmed and 10 wild). delta(13)C and delta(15)N values have
      been measured on muscle samples as these are the most informative parameters of
      the diet of the animals. Both stable isotopes are indicators of the origin of the
      fish: delta(13)C giving a tool to distinguish between wild and farmed g.s.b. and
      delta(15)N being more informative on the geographical origin of the fish (this
      fact could be related more to differences in feed mixtures given to farmed fish
      than to geographical reasons). The proposed methodology offers a cost- and time
      effective alternative to other analytical techniques in identifying wild and
      farmed fish.

PMID- 17171780
TI  - Validation and application of a screening method for beta2-agonists, anti
      estrogenic substances and mesocarb in human urine using liquid
      chromatography/tandem mass spectrometry.
AB  - Electrospray ionization (ESI) mass spectra of 15 anti-estrogenic substances,
      beta2-agonists and mesocarb were investigated in terms of fragmentation patterns.
      On the basis of this product ion information, a simultaneous screening method for
      anti-estrogenic substances, beta2-agonists and mesocarb was developed for doping
      control purposes. After hydrolysis, liquid-liquid extraction was adopted for the
      sample preparation. The recoveries for all compounds were 30 and 96%. A single
      liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis could be
      performed in 13 min for the analysis of 15 anti-estrogenic substances, beta2
      agonists and mesocarb. A quantitative analysis was also validated. Inaccuracies
      were below +/-12% and precisions varied from 0 to 15.8%. The limit of detection
      was below 10 ng/mL except formestane (300 ng/mL) and aminoglutethimide (100
      ng/mL). The validated method was applied for the analysis of excretion samples.

PMID- 17171781
TI  - Structural assignment of disialylated biantennary N-glycan isomers derivatized
      with 2-aminopyridine using negative-ion multistage tandem mass spectral matching.
AB  - To investigate the possibility of structural assignment based on negative-ion
      multistage tandem mass (MS(n)) spectral matching, four isomers of disialylated
      biantennary N-glycans (alpha2-6 and/or alpha2-3 linked sialic acid on alpha1-6
      and alpha1-3 antennae) derivatized with 2-aminopyridine (PA) were analyzed by
      employing high-performance liquid chromatography/electrospray ionization linear
      ion trap time-of-flight mass spectrometry (HPLC/ESI-LIT-TOFMS), which uses helium
      gas for ion trapping and collision-induced dissociation (CID). It is shown that
      the MS(2) spectra derived from each precursor ion [M-2H](2-) are reproducible and
      useful for distinguishing the four isomers. Thus, they can be assigned by
      negative-ion MS(2) spectral matching based on correlation coefficients. In
      addition, MS(3) spectra derived from D-type fragment ions clearly differentiate
      the alpha2-3- or alpha2-6-linked sialic acid on the alpha1-6 antenna due to their
      characteristic spectral patterns. The C(4)-type fragment ions, which are produced
      from both the alpha1-6 and alpha1-3 antennae, show the characteristic MS(3)
      spectra reflecting alpha2-3- or alpha2-6- linkage type or a mixture of both
      types. Thus, the differentiation and assignment of these disialylated biantennary
      N-glycan isomers can also be supported with the MS(3) spectra of C(4)- and D-type
      ions.

PMID- 17171782
TI  - Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus.
AB  - The prognosis of patients with hepatocellular carcinoma (HCC) accompanied by
      portal vein tumor thrombus (PVTT) is generally poor if left untreated: a median
      survival time of 2.7-4.0 mo has been reported. Furthermore, while transcatheter
      arterial chemoembolization (TACE) has been shown to be safe in selected patients,
      the median survival time with this treatment is still only 3.8-9.5 mo. Systemic
      single-agent chemotherapy for HCC with PVTT has failed to improve the prognosis,
      and the response rates have been less than 20%. While regional chemotherapy with
      low-dose cisplatin and 5-fluorouracil or interferon and 5-fluorouracil via
      hepatic arterial infusion has increased the response rate, the median survival
      time has not exceeded 12 (range 4.5-11.8) mo. Combined treatment consisting of
      radiation for PVTT and TACE for liver tumor has achieved a high response rate,
      but the median survival rates have still been only 3.8-10.7 mo. With hepatic
      resection as monotherapy, the 5-year survival rate and median survival time were
      reportedly 4%-28.5% and 6-14 mo. The most promising results were reported for
      combined treatments consisting of hepatectomy and TACE, chemotherapy, or internal
      radiation. The reported 5-year survival rates and median survival times were 42%
      and 31 mo for TACE followed by hepatectomy; 36.3% and 22.1 mo for hepatectomy
      followed by hepatic arterial infusion chemotherapy; and 56% for chemotherapy or
      internal radiation followed by hepatectomy.

PMID- 17171783
TI  - Positions of selective leukocytapheresis in the medical therapy of ulcerative
      colitis.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of
      idiopathic inflammatory bowel disease (IBD). Both UC and CD are debilitating
      chronic disorders that afflict millions of individuals throughout the world with
      symptoms which impair function and quality of life. The etiology of IBD is
      inadequately understood and therefore, drug therapy has been empirical instead of
      being based on sound understanding of IBD pathogenesis. This is a major factor
      for poor drug efficacy and drug related side effects that often add to the
      disease complexity. The development of biologicals notably infliximab to
      intercept tumor necrosis factor (TNF)-alpha reflects some progress, albeit major
      concern about their side effects and lack of long-term safety and efficacy
      profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF
      alpha, interleukin (IL)-1beta, IL-6 and IL-8 for which activated peripheral
      granulocytes and monocytes/macrophages (GM) are major sources. Further, in IBD,
      peripheral GMs are elevated with activation behavior, increased survival time and
      are found in vast numbers within the inflamed intestinal mucosa; they are
      suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral
      blood GMs should be appropriate targets of therapy. The Adacolumn is a medical
      device developed for selective depletion of GM by receptor-mediated adsorption
      (GMA). Clinical data show GMA, in patients with steroid dependent or steroid
      refractory UC, is associated with up to 85% efficacy and tapering or
      discontinuation of steroids, while in steroid naive patients (the best
      responders), GMA spares patients from exposure to steroids. Likewise, GMA at
      appropriate intervals in patients at a high risk of clinical relapse suppresses
      relapse thus sparing the patients from the morbidity associated with IBD relapse.
      Further, GMA appears to reduce the number of patients being submitted to
      colectomy or exposure to unsafe immunosupressants. First UC episode, steroid
      naivety and short disease duration appear good predictors of response to GMA and
      based on the available data, GMA seems to have an excellent safety profile.

PMID- 17171784
TI  - Aging and the intestine.
AB  - Over the lifetime of the animal, there are many changes in the function of the
      body's organ systems. In the gastrointestinal tract there is a general modest
      decline in the function of the esophagus, stomach, colon, pancreas and liver. In
      the small intestine, there may be subtle alterations in the intestinal
      morphology, as well as a decline in the uptake of fatty acids and sugars. The
      malabsorption may be partially reversed by aging glucagon-like peptide 2 (GLP2)
      or dexamethasone. Modifications in the type of lipids in the diet will influence
      the intestinal absorption of nutrients: for example, in mature rats a diet
      enriched with saturated as compared with polysaturated fatty acids will enhance
      lipid and sugar uptake, whereas in older animals the opposite effect is observed.
      Thus, the results of studies of the intestinal adaptation performed in mature
      rats does not necessarily apply in older animals. The age-associated
      malabsorption of nutrients that occurs with aging may be one of the several
      factors which contribute to the malnutrition that occurs with aging.

PMID- 17171785
TI  - Persistent CXCR4 expression after preoperative chemoradiotherapy predicts early
      recurrence and poor prognosis in esophageal cancer.
AB  - AIM: To study the effect of CXC chemokine receptor-4 (CXCR4) expression on
      disease progression and prognosis in esophageal cancer. METHODS: CXCR4 expression
      was evaluated in 37 patients with histologically confirmed esophageal squamous
      carcinomas (ESCC) undergoing preoperative chemoradiotherapy (CRT) by
      immunohistochemical staining. RESULTS: Eleven out of 37 ESCC patients showed a
      pathological complete response (CR) after CRT. CXCR4 protein expression was
      observed in cell cytoplasms of 13 tumors, and null expression was seen in 13
      tumors. Distant recurrence was significantly more common in patients with
      positive CXCR4 expression (P = 0.0318). After a median follow-up time of 31.6 mo,
      19 patients progressed (12 of 19 expressed positive CXCR4) and 11 died (10 of 11
      expressed positive CXCR4). Overall survival was significantly correlated with
      lymph node metastasis (952.1 +/- 53.8 d in negative group vs 475.1 +/- 56.2 d in
      positive group, P = 0.023), distant metastasis (874.0 +/- 60.4 d in negative
      group vs 434.9 +/- 75.2 d in positive group, P = 0.014) and CRT (811.5 +/- 51.2 d
      in responder group vs 459.6 +/- 94.0 d in non-responder group, P = 0.00038) and
      further with an absence of CXCR4 expression or no residual tumor (959.8 +/- 51.0
      d in null expression or no tumor group vs 412.0 +/- 57.1 d in positive expression
      group, P = 0.0001). CONCLUSION: Persistent positive CXCR4 expression is
      implicated in tumor aggressiveness and poor prognosis in ESCC after CRT, and
      preoperative CRT may improve the prognosis of ESCC via CXCL12-CXCR4 signaling
      pathway.

PMID- 17171786
TI  - Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase
      polymorphisms are associated with gastric carcinogenesis.
AB  - AIM: To evaluate whether folate levels in mucosal tissue and some common
      methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk
      of gastric cancer through DNA methylation. METHODS: Real-time PCR was used to
      study the expression of tumor related genes in 76 mucosal tissue samples from 38
      patients with gastric cancer. Samples from the gastroscopic biopsy tissues of 34
      patients with chronic superficial gastritis (CSG) were used as controls. Folate
      concentrations in these tissues were detected by the FOL ACS:180 automated
      chemiluminescence system. MTHFR polymorphisms were analyzed by PCR-RFLP, and the
      promoter methylation of tumor-related genes was determined by methylation
      specific PCR (MSP). RESULTS: Folate concentrations were significantly higher in
      CSG than in cancerous tissues. Decreased expression and methylation of c-myc
      accompanied higher folate concentrations. Promoter hypermethylation and loss of
      p16(INK4A) in samples with MTHFR 677CC were more frequent than in samples with
      the 677TT or 677CT genotype. And the promoter hypermethylation and loss of
      p21(WAF1) in samples with MTHFR 677CT were more frequent than when 677CC or 677TT
      was present. The 677CT genotype showed a non-significant higher risk for gastric
      cancer as compared with the 677CC genotype. CONCLUSION: Lower folate levels in
      gastric mucosal tissue may confer a higher risk of gastric carcinogenesis through
      hypomethylation and overexpression of c-myc.

PMID- 17171787
TI  - Microvessel density is a prognostic marker of human gastric cancer.
AB  - AIM: To investigate whether microvessel density (MVD) is related with prognosis
      in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and
      vessel endothelial growth factor (VEGF) so as to determine the possible role of
      COX-2 and VEGF in gastric cancer angiogenesis. METHODS: Forty-seven formalin
      fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX
      2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was
      determined by immunohitochemical staining of endothelial protein factor VIII
      related antigen. The relationship among COX-2 and VEGF expression, MVD, and
      clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high
      MVD was significantly associated with lymph node metastasis and poor survival.
      Multivariate survival analysis showed that MVD value and lymph node metastasis
      were independent prognostic factors. The expression rate of COX-2 and VEGF was
      significantly higher than that of the adjacent tissues. COX-2 and VEGF expression
      in gastric cancer was significantly correlated with tumor differentiation and
      depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF
      positive tumors was higher than that of COX-2 or VEGF negative tumors. A
      significant correlation was found between the expressions of COX-2 and VEGF.
      CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer
      patients. COX-2 and VEGF may play an important role in tumor progression by
      stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic
      pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an
      important therapeutic benefit in the control of gastric cancer.

PMID- 17171789
TI  - Antitumor activity of an hTERT promoter-regulated tumor-selective oncolytic
      adenovirus in human hepatocellular carcinoma.
AB  - AIM: To construct a tumor-selective replication-competent adenovirus (RCAd),
      SG300, using a modified promoter of human telomerase reverse transcriptase
      (hTERT). METHODS: The antitumor efficacy of SG300 in hepatocellular carcinoma was
      assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to
      assess the tumor-selective oncolysis and safety features of SG300, and in vivo
      antitumor activity of SG300 was assessed in established hepatocellular carcinoma
      models in nude mice. RESULTS: SG300 could lyse hepatocellular carcinoma cells at
      a low multiplicity of infection (MOI), but could not affect growth of normal
      cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of
      hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a
      decrease in tumor volume. Its selective oncolysis to tumor cells and safety to
      normal cells was also superior to that of ONYX-015. Pathological examination of
      tumor specimens showed that SG300 replicated selectively in cancer cells and
      resulted in apoptosis and necrosis of cancer cells. CONCLUSION: hTERT promoter
      regulated replicative adenovirus SG300 has a better cancer-selective replication
      competent ability, and can specifically kill a wide range of cancer cells with
      positive telomerase activity, and thus has better potential for targeting therapy
      of hepatocellular carcinoma.

PMID- 17171788
TI  - New multi protein patterns differentiate liver fibrosis stages and hepatocellular
      carcinoma in chronic hepatitis C serum samples.
AB  - AIM: To identify a multi serum protein pattern as well as single protein markers
      using surface-enhanced laser desorption/ionisation time-of-flight mass
      spectrometry (SELDI-TOF-MS) for detection and differentiation of liver fibrosis
      (F1-F2), liver cirrhosis (F4) and hepatocellular carcinoma (HCC) in patients with
      chronic hepatitis C virus (HCV). METHODS: Serum samples of 39 patients with F1/F2
      fibrosis, 44 patients with F4 fibrosis, 34 patients with HCC were applied to CM10
      arrays and analyzed using the SELDI-TOF ProteinChip System (PBS-IIc; Ciphergen
      Biosystems) after anion-exchange fractionation. All patients had chronic
      hepatitis C and histologically confirmed fibrosis stage/HCC. Data were analyzed
      for protein patterns by multivariate statistical techniques and artificial neural
      networks. RESULTS: A 4 peptide/protein multimarker panel (7486, 12,843, 44,293
      and 53,598 Da) correctly identified HCCs with a sensitivity of 100% and
      specificity of 85% in a two way-comparison of HCV-cirrhosis versus HCV-HCC
      training samples (AUROC 0.943). Sensitivity and specificity for identification of
      HCC were 68% and 80% for random test samples. Cirrhotic patients could be
      discriminated against patients with F1 or F2 fibrosis using a 5 peptide/protein
      multimarker pattern (2873, 6646, 7775, 10,525 and 67,867 Da) with a specificity
      of 100% and a sensitivity of 85% in training samples (AUROC 0.976) and a
      sensitivity and specificity of 80% and 67% for random test samples. Combination
      of the biomarker classifiers with APRI score and alfa-fetopotein (AFP) improved
      the diagnostic performance. The 6646 Da marker protein for liver fibrosis was
      identified as apolipoprotein C-I. CONCLUSION: SELDI-TOF-MS technology combined
      with protein pattern analysis seems a valuable approach for the identification of
      liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis
      C. Most probably a combination of different serum markers will help to identify
      liver cirrhosis and early-stage hepatocellular carcinomas in the future.

PMID- 17171790
TI  - Bone morphogenetic protein-2 is a negative regulator of hepatocyte proliferation
      downregulated in the regenerating liver.
AB  - AIM: To characterize the expression and dynamic changes of bone morphogenetic
      protein (BMP)-2 in hepatocytes in the regenerating liver in rats after partial
      hepatectomy (PH), and examine the effects of BMP-2 on proliferation of human Huh7
      hepatoma cells. METHODS: Fifty-four adult male Wistar rats were randomly divided
      into three groups: A normal control (NC) group, a partial hepatectomized (PH)
      group and a sham operated (SO) group. To study the effect of liver regeneration
      on BMP-2 expression, rats were sacrificed before and at different time points
      after PH or the sham intervention (6, 12, 24 and 48 h). For each time point, six
      rats were used in parallel. Expression and distribution of BMP-2 protein were
      determined in regenerating liver tissue by Western blot analysis and
      immunohistochemistry. Effects of BMP-2 on cell proliferation of human Huh7
      hepatoma cell line were assessed using an MTT assay. RESULTS: In the normal liver
      strong BMP-2 expression was observed around the central and portal veins. The
      expression of BMP-2 decreased rapidly as measured by both immunohistochemistry
      and Western blot analysis. This decrease was at a maximum of 3.22 fold after 12 h
      and returned to normal levels at 48 h after PH. No significant changes in BMP-2
      immunoreactivity were observed in the SO group. BMP-2 inhibited serum induced
      Huh7 cell proliferation. CONCLUSION: BMP-2 is expressed in normal adult rat liver
      and negatively regulates hepatocyte proliferation. The observed down regulation
      of BMP-2 following partial hepatectomy suggests that such down regulation may be
      necessary for hepatocyte proliferation.

PMID- 17171792
TI  - Sorbitol-based osmotic diarrhea: possible causes and mechanism of prevention
      investigated in rats.
AB  - AIM: To study the possible causes of sorbitol (S)-based diarrhea and its
      mechanism of reduction by rice gruel (RG) in cecectomized rats. METHODS: S was
      dissolved either in distilled water or in RG (50 g/L) and ingested as a single
      oral dose (1.2 g/kg body mass, containing 0.5 g/L phenol red as a recovery
      marker) by S (control) and S + RG groups (n = 7), respectively. This dose is over
      the laxative dose for humans. Animals were sacrificed exactly 1 h after dose
      ingestion, without any access to drinking water. The whole gastro-intestinal
      tract was divided into seven segments and sampled to analyze the S and marker
      remaining in its contents. RESULTS: Gastric-emptying and intestinal transit were
      comparatively slower in the S + RG group. Also, the S absorption index in the
      3(rd) and last quarter of the small intestine (24.85 +/- 18.88% vs 0.0 +/- 0.0%
      and 39.09 +/- 32.75% vs 0.0 +/- 0.0%, respectively, P < 0.05) was significantly
      higher in the S + RG group than in the control group. The S absorption index and
      the intestinal fluid volume are inversely related to each other. CONCLUSION: The
      intestinal mal-absorption of S is the main reason for S-based osmotic diarrhea.
      Where RG enhanced the absorption of S through passive diffusion, the degree of
      diarrhea was reduced in cecectomized rats.

PMID- 17171791
TI  - Expression patterns and action analysis of genes associated with hepatitis virus
      infection during rat liver regeneration.
AB  - AIM: To study the action of hepatitis virus infection-associated genes at
      transcription level during liver regeneration (LR). METHODS: Hepatitis virus
      infection-associated genes were obtained by collecting the data from databases
      and retrieving the correlated articles, and their expression changes in the
      regenerating rat liver were detected with the rat genome 230 2.0 array. RESULTS:
      Eighty-eight genes were found to be associated with liver regeneration. The
      number of genes initially and totally expressed during initial LR [0.5-4 h after
      partial hepatectomy (PH)], transition from G0 to G1 (4-6 h after PH), cell
      proliferation (6-66 h after PH), cell differentiation and reorganization of
      structure-function (66-168 h after PH) was 37, 8, 48, 3 and 37, 26, 80, 57,
      respectively, indicating that the genes were mainly triggered at the early stage
      of LR (0.5-4 h after PH), and worked at different phases. These genes were
      classified into 5 types according to their expression similarity, namely 37 up
      regulated, 9 predominantly up-regulated, 34 down-regulated, 6 predominantly down
      regulated and 2 up/down-regulated genes. Their total up- and down-regulation
      frequencies were 359 and 149 during LR, indicating that the expression of most
      genes was enhanced, while the expression of a small number of genes was
      attenuated during LR. According to time relevance, they were classified into 12
      groups (0.5 and 1 h, 2 and 4 h, 6 h, 8 and 12 h, 16 and 96 h, 18 and 24 h, 30 and
      42 h, 36 and 48 h, 54 and 60 h, 66 and 72 h, 120 and 144 h, 168 h), demonstrating
      that the cellular physiological and biochemical activities during LR were
      fluctuated. According to expression changes of the genes, their expression
      patterns were classified into 23 types, suggesting that the cellular
      physiological and biochemical activities during LR were diverse and complicated.
      CONCLUSION: The anti-virus infection capacity of regenerating liver can be
      enhanced and 88 genes play an important role in LR.

PMID- 17171793
TI  - Effective regularity in modulation on gastric motility induced by different
      acupoint stimulation.
AB  - AIM: To investigate whether manual acupuncture at representative acupoints in
      different parts of the body can modulate responses of gastric motility in rats
      and regular effects in different acupoint stimulation. METHODS: The gastric motor
      activity of rats was recorded by the intrapyloric balloon. The changes of gastric
      motility induced by the stimulation were compared with the background activity in
      intragastric pressure and/or waves of gastric contraction recorded before any
      stimulation. Morphological study was also conducted by observing the Evans dye
      extravasation in the skin after mustard oil injection into the intragastric
      mucous membrane to certify cutaneous innervations of blue dots related to gastric
      segmental innervations. RESULTS: In all six rats that received mustard oil
      injections into intragastric mucosa, small blue dots appeared in the skin over
      the whole abdomen, but mainly in peri-midline upper- and middle- abdomen and
      middle-back, a few in thigh and groin. It may speculate that cutaneous
      innervations of blue dots have the same distribution as gastric segmental
      innervations. Acu-stimulation in acupoints of head-neck, four limbs, upper chest
      dorsum and lower-dorsum induced markedly augmentation of gastric motility
      (acupoints on head-neck such as St-2: n = 16, 105.19 +/- 1.36 vs 112.25 +/- 2.02
      and St-3: n = 14, 101.5 +/- 1.75 vs 109.36 +/- 1.8; acupoints on limbs such as Sp
      6: n = 19, 100.74 +/- 1.54 vs 110.26 +/- 3.88; St-32: n = 17, 103.59 +/- 1.64 vs
      108.24 +/- 2.41; St-36: n = 16, 104.81 +/- 1.72 vs 110.81 +/- 2.74 and Li-11: n =
      17, 106.47 +/- 2.61 vs 114.77 +/- 3.77, P < 0.05-0.001). Vigorous inhibitory
      regulations of gastric motility induced by acu-stimulation applied in acupoints
      on whole abdomen and middle-dorsum were significantly different as compared with
      the controls before acu-stimulation (abdomen acupoints such as Cv-12: n = 11,
      109.36 +/- 2.09 vs 101 +/- 2.21; Cv-6: n = 18, 104.39 +/- 1.42 vs 91.83 +/- 3.22
      and St-21: n = 12, 107 +/- 2.97 vs 98.58 +/- 2.81; acupoints on middle-dorsum
      such as Bl-17: n = 19, 100.63 +/- 1.4 vs 92.21 +/- 2.07 and Bl-21: n = 19, 103.84
      +/- 1.48 vs 97.58 +/- 2.16, P < 0.05-0.001). CONCLUSION: Regular regulatory
      effects of facilitation and inhibition on gastric motility appear to be
      somatotopically organized in the acupoints of whole body, and the effective
      regularity of site-special acupoints on gastric motility is involved in segmental
      innervations between stomach and acupoints.

PMID- 17171794
TI  - Construction of a fusion protein expression vector MK-EGFP and its subcellular
      localization in different carcinoma cell lines.
AB  - AIM: To construct an expression plasmid encoding human wild-type midkine (MK) and
      enhanced green fluorescence protein (EGFP) fusion protein (MK-EGFP), and to
      analyze the subcellular localization of MK in different carcinoma cell lines.
      METHODS: Two kinds of MK coding sequences with or without signal peptide were
      cloned into plasmid pEGFP-N2, and the recombinant plasmids constructed were
      introduced into HepG2, MCF7 and DU145 cells, respectively, by transfection. With
      the help of laser scanning confocal microscopy, the expression and subcellular
      localization of MK-GFP fusion protein could be detected. RESULTS: Compared with
      the GFP control, in which fluorescence was detected diffusely over the entire
      cell body except in the nucleolus, both kinds of fusion protein MK-GFP were
      localized exclusively to the nucleus and accumulated in the nucleolus in the
      three kinds of cancer cell lines. CONCLUSION: This study reveals the specific
      nucleolar translocation independent of signal peptide, which may be involved in
      the mechanism that MK works. It provides valuable evidence for further study on
      the functions of MK in nucleus and its possible mechanisms, in which ribosomal
      RNA transcription and ribosome assembly are involved.

PMID- 17171795
TI  - Double-balloon endoscopy in the diagnosis and management of GI tract diseases:
      Methodology, indications, safety, and clinical impact.
AB  - AIM: To prospectively evaluate the indications, methodology, safety, and clinical
      impact of double-balloon endoscopy. METHODS: A total of 60 patients with
      suspected or documented small- or large-bowel diseases were investigated by
      double balloon endoscopy. A total of 103 procedures were performed (42 from the
      oral route, 60 from the anal route, and 1 from the stoma route). The main outcome
      measurements were the time of insertion and the entire examination,
      complications, diagnostic yields, and the ability to successfully perform
      treatment. RESULTS: Observation of the entire small intestine was possible in 10
      (40%) of 25 patients with total enteroscopy. The median insertion time was 122
      min (range, 74-199 min). Observation of the entire colon was possible in 13 (93%)
      of 14 patients after failure of total colonoscopy using a conventional
      colonoscope. Small-intestine abnormalities were found in 20 (43%) of 46 patients
      with indications of suspected or documented small bowel diseases, obscure GI
      tract bleeding, or a history of ileus. Endoscopic procedures including tattooing
      (n = 33), bite biopsy (n = 17), radiographic examination (n = 7), EUS (n = 5),
      hemostasis (n = 1), polypectomy (n = 5), balloon dilatation (n = 1), endoscopic
      mucosal resection (n = 1) and lithotripsy (n = 1) were all successfully
      performed. No relevant technical problems or severe complications were
      encountered. CONCLUSION: Double balloon endoscopy is a feasible technique that
      allows adequate small and large bowel examination and potentially various
      endoscopic procedures of small-intestinal lesions. It is safe, useful, and also
      provides a high clinical impact.

PMID- 17171796
TI  - Sampling variability of computer-aided fractal-corrected measures of liver
      fibrosis in needle biopsy specimens.
AB  - AIM: To assess the sampling variability of computer-aided, fractal-corrected
      measures of fibrosis in liver biopsies. METHODS: Samples were derived from six to
      eight different parts of livers removed from 12 patients with clinically and
      histologically proven cirrhosis undergoing orthotopic liver transplantation.
      Sirius red-stained sections with a thickness of 2 mum were digitized using a
      computer-aided image analysis system that automatically measures the surface of
      fibrosis, as well as its outline perimeter, fractal surface and outline
      dimensions, wrinkledness, and Hurst coefficient. RESULTS: We found a high degree
      of inter-sample variability in the measurements of the surface [coefficient of
      variation (CV) = 43% +/- 13%] and wrinkledness (CV = 28% +/- 9%) of fibrosis, but
      the inter-sample variability of Hurst's exponent was low (CV = 14% +/- 2%).
      CONCLUSION: This study suggests that Hurst's exponent might be used in clinical
      practice as the best histological estimate of fibrosis in the whole organ, and
      evidences the fact that biopsy sections, which are fundamental for the
      qualitative diagnosis of chronic hepatitis, play a key role in the quantitative
      estimate of architectural changes in liver tissue.

PMID- 17171797
TI  - Blockade of high mobility group box-1 protein attenuates experimental severe
      acute pancreatitis.
AB  - AIM: To examine the effects of anti-high mobility group box 1 (HMGB1)
      neutralizing antibody in experimental severe acute pancreatitis (SAP). METHODS:
      SAP was induced by creating closed duodenal loop in C3H/HeN mice. SAP was induced
      immediately after intraperitoneal injection of anti-HMGB1 neutralizing antibody
      (200 microg). Severity of pancreatitis, organ injury (liver, kidney and lung),
      and bacterial translocation to pancreas was examined 12 h after induction of SAP.
      RESULTS: Anti-HMGB1 neutralizing antibody significantly improved the elevation of
      the serum amylase level and the histological alterations of pancreas and lung in
      SAP. Anti-HMGB1 antibody also significantly ameliorated the elevations of serum
      alanine aminotransferase and creatinine in SAP. However, anti-HMGB1 antibody
      worsened the bacterial translocation to pancreas. CONCLUSION: Blockade of HMGB1
      attenuated the development of SAP and associated organ dysfunction, suggesting
      that HMGB1 may act as a key mediator for inflammatory response and organ injury
      in SAP.

PMID- 17171798
TI  - Defensive medicine practices among gastroenterologists in Japan.
AB  - AIM: To clarify the prevalence of defensive medicine and the specific defensive
      medicine practices among gastroenterologists in Japan. METHODS: A survey of
      gastroenterologists in Hiroshima, Japan, was conducted by mail in March 2006. The
      number of gastroenterologists reporting defensive medicine behaviors or changes
      in their scope of practice and the reported defensive medicine practices, i.e.,
      assurance and avoidance behaviors, were examined. RESULTS: A total of 131 (77%)
      out of 171 gastroenterologists completed the survey. Three (2%) respondents were
      sued, and most respondents (96%) had liability insurance. Nearly all respondents
      (98%) reported practicing defensive medicine. Avoidance behaviors, such as
      avoiding certain procedures or interventions and avoiding caring for high-risk
      patients, were very common (96%). Seventy-five percent of respondents reported
      often avoiding certain procedures or interventions. However, seasoned
      gastroenterologists (those in practice for more than 20 years) adopted avoidance
      behaviors significantly less often than those in practice for less than 10 years.
      Assurance behaviors, i.e., supplying additional services of marginal or no
      medical value, were also widespread (91%). Sixty-eight percent of respondents
      reported that they sometimes or often referred patients to other specialists
      unnecessarily. CONCLUSION: Defensive medicine may be highly prevalent among
      gastroenterologists throughout Japan, with potentially serious implications
      regarding costs, access, and both technical and interpersonal quality of care.

PMID- 17171799
TI  - Meta-analysis of short-term outcomes after laparoscopy-assisted distal
      gastrectomy.
AB  - AIM: To elucidate the current status of laparoscopy-assisted distal gastrectomy
      (LADG) with regard to its short-term outcomes by comparing it with conventional
      open distal gastrectomy (CODG). METHODS: Original articles published from January
      1991 to August 2006 were searched in the MEDLINE, EMBASE, and Cochrane Controlled
      Trials Register. Clinical appraisal and data extraction were conducted
      independently by 2 reviewers. A meta-analysis was performed using a random
      effects model. RESULTS: Outcomes of 1611 procedures from 4 randomized controlled
      trials and 12 retrospective studies were analyzed. Compared to CODG, LADG was a
      longer procedure (weighted mean difference [WMD] 54.3; 95% confidence interval
      [CI] 38.8 to 69.8; P < 0.001), but was associated with a lower associated
      morbidity (odds ratio [OR] 0.54; 95% CI 0.37 to 0.77; P < 0.001); this was most
      significant for postoperative ileus (OR 0.27; 95% CI 0.09 to 0.84; P = 0.02).
      There was no significant difference between the two groups in anastomotic,
      pulmonary, and wound complications and mortality. Duration from surgery to first
      passage of flatus was faster (WMD -0.68; 95% CI -0.85 to -0.50; P < 0.001) and
      the frequency of additional analgesic requirement (WMD -1.36; 95% CI -2.44 to 
      0.28; P = 0.01), and duration of hospital stay (WMD -5.51; 95% CI -7.61 to -3.42;
      P < 0.001) were significantly lower after LADG. However, a significantly higher
      number of lymph nodes were dissected by CODG (WMD -4.35; 95% CI -5.73 to -2.98; P
      < 0.001). CONCLUSION: LADG for early gastric cancer is associated with a lower
      morbidity, less pain, faster bowel function recovery, and shorter hospital stay.

PMID- 17171800
TI  - Differences in characteristics of colorectal neoplasm between young and elderly
      Thais.
AB  - AIM: To analyze the differences of clinical characteristics of colorectal
      neoplasm including polyps between the elderly and young Thai patients. METHODS:
      Colonoscopy database from December 2000 to October 2004 was retrospectively
      analyzed. There were 1822 eligible patients who underwent colonoscopy (with a
      mean age of 56.6 years). Patients were classified into two groups: the older age
      group (aged > or = 60 years; n = 989) and the younger age group (aged < 60 years;
      n = 833). Data were recorded on age, colonoscopic indications, tumor location,
      colonoscopic findings and their related histological findings. RESULTS:
      Colorectal malignancy related lesions were more often found in the older age
      group (21%) than in the younger age group (12%). Left-sided lesions were detected
      more commonly than right-sided in both age groups in approximately two-thirds of
      all cases. Hematochezia showed greater association with left-sided lesions in the
      elderly. No relationship was found between age and neoplasm staging and severity.
      CONCLUSION: The chance of detecting colorectal neoplasm by colonoscopy was higher
      in the elderly than in the young Thais. However, both groups had the lesions
      predominantly located in the left side.

PMID- 17171801
TI  - Non-invasive measurement of pan-colonic pressure over a whole digestive cycle:
      clinical applications of a capsule-style manometric system.
AB  - AIM: To study the prolonged colonic motility under normal conditions with a novel
      capsule-style micro-system and to assess its clinical significance. METHODS: A
      single use telemetry capsule (10 mm in diameter, 20 mm in length) embedded with a
      pressure sensor was ingested by the subjects. The sensor is capable of
      transmitting colonic pressure wirelessly for more than 130 h. The time of capsule
      entering the segmental colon was detected by ultrasound. The ultrasonic
      electrodes were mounted on the surface of the ileocecum and navel and at the
      junction of the left and rectosigmoid colon of the subjects in sequence, which
      were identified by abdominal X-rays with radiopaque markers. To verify the
      accuracy and reliability of ultrasonic detection of telemetry capsules at key
      points of colon, the segmental colonic transit time was simultaneously recorded
      by using radiopaque markers. RESULTS: The signal lamp showed that all recorders
      could receive the radio signal transmitted by the telemetry capsule. The X-rays
      showed that all telemetry capsules were detected successfully when they were
      passing through the key points of colon. There was a significant correlation
      between the transit results obtained by ultrasonic detection or by radiopaque
      markers. Colorectal recording was obtained from 20 healthy subjects during 613 h
      (411 h during waking, 202 h during sleep). Compared to waking, the number of
      pressure contractions and the area under pressure contractions were significantly
      (P < 0.05) decreased during sleep (21 +/- 5 h(-1) vs 15 +/- 4 h(-1), 463 +/- 54
      mmHg x s/min vs 342 +/- 45 mmHg x s/min). The colonic motility exhibited
      significant regional variations both in the circadian behavior and in response to
      waking and meal. CONCLUSION: The capsule-style micro-system is reliable and
      noninvasive, and may represent a useful tool for the study of physiology and
      pathology of colonic motor disorders.

PMID- 17171802
TI  - Expression of ATP7B in human gastric cardiac carcinomas in comparison with distal
      gastric carcinomas.
AB  - AIM: To analyze expression of ATP7B in gastric cardiac adenocarcinomas, its
      clinicopathologic significance, in comparison with distal gastric
      adenocarcinomas. METHODS: Immunohistochemical avidin-biotin peroxidase complex
      method was applied to detect the expression of ATP7B in 49 cases of cardiac
      carcinomas, the corresponding adjacent non-neoplastic epithelium and 55 cases of
      distal gastric carcinomas. RESULTS: The proportion of ATP7B positive samples in
      gastric cardiac carcinomas (51.0%, 25 of 49) was significantly higher than that
      in the corresponding adjacent non-neoplastic epithelium (22.4%, 11 of 49) (P =
      0.003). ATP7B expression in poorly differentiated gastric cardiac carcinomas was
      significantly higher than that in well/moderately differentiated gastric cardiac
      carcinomas (P = 0.030). ATP7B expression in gastric cardiac carcinomas was
      independent of age, tumor size, nodal stage and metastasis status. ATP7B protein
      was detected in 30.9% (17/55 cases) of distal gastric carcinomas, markedly lower
      than that in gastric cardiac carcinomas (P = 0.037). CONCLUSION: ATP7B protein is
      frequently overexpressed in gastric cardiac carcinomas, and correlated with the
      differentiation of cardiac carcinoma. ATP7B expression in gastric cardiac
      carcinomas is significantly higher than that in distal gastric carcinomas, which
      might partially explain the difference of chemotherapy response and prognosis
      between these two gastric carcinomas.

PMID- 17171803
TI  - Myoelectric activity and motility of the Roux limb after cut or uncut Roux-en-Y
      gastrojejunostomy.
AB  - AIM: To explore the mechanisms of uncut Roux-en-Y gastrojejunostomy, which is
      used to decrease the occurrence of Roux stasis syndrome. METHODS: The changes of
      myoelectric activity, mechanic motility and interstitial cells of Cajal (ICC) of
      the Roux limb after cut or uncut Roux-en-Y gastrojejunostomy were observed.
      RESULTS: When compared with the cut group, the amplitude (1.15 +/- 0.15 mV vs
      0.48 +/- 0.06 mV, P < 0.05) and frequency (14.4 +/- 1.9 cpm vs 9.5 +/- 1.1 cpm, P
      < 0.01) of slow waves and the incidence (98.2% +/- 10.4% vs 56.6% +/- 6.4%, P <
      0.05) and amplitude (0.58 +/- 0.08 mV vs 0.23 +/- 0.06 mV, P < 0.01) of spike
      potential of the Roux limb in the uncut group were significantly higher. The
      migrating myoelectric complexes (MMC) phase III duration in the uncut group was
      significantly prolonged (6.5 +/- 1.1 min vs 4.4 +/- 0.8 min, P < 0.05), while the
      MMC cycle obviously shortened (42.5 +/- 6.8 vs 55.3 +/- 8.2 min, P < 0.05). Both
      gastric emptying rate (65.5% +/- 7.9% vs 49.3% +/- 6.8%, P < 0.01) and intestinal
      impelling ratio (53.4% +/- 7.4% vs 32.2% +/- 5.4%, P < 0.01) in the uncut group
      were significantly increased. The contractile force index of the isolated jejunal
      segment in the uncut group was significantly higher (36.8 +/- 5.1 vs 15.3 +/-
      2.2, P < 0.01), and the expression of c-kit mRNA was significantly increased in
      the uncut group (0.82 +/- 0.11 vs 0.35 +/- 0.06, P < 0.01). CONCLUSION: Uncut
      Roux-en-Y gastrojejunostomy may lessen the effects of operation on myoelectric
      activity such as slow waves, spike potential, and MMC, decrease the impairment of
      gastrointestinal motility, and remarkably increase the expression of c-kit mRNA.

PMID- 17171804
TI  - Ligustrazine alleviates acute renal injury in a rat model of acute necrotizing
      pancreatitis.
AB  - AIM: To evaluate the effect of ligustrazine, a traditional Chinese medicine, on
      renal injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS: A
      total of 192 rats were randomly divided into three groups: control (C group), ANP
      without treatment (P group), and ANP treated with ligustrazine (T group). Each
      group was further divided into 0.5, 2, 6, 12 h subgroups. All rats were
      anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium
      taurocholate was infused through the pancreatic membrane to induce ANP. T group
      was infused sodium taurocholate as above, and 0.6% ligustrazine was then
      administered via the femoral vein. Serum urea nitrogen (BUN) and creatinine (Cr)
      concentrations were measured for the evaluation of renal function. The effects of
      ligustrazine on the severity of renal injury were assessed by renal function,
      TXA(2)/PGI(2) and histopathological changes. Renal blood flow was determined by
      the radioactive microsphere technique (RMT). RESULTS: Compared with control
      group, the renal blood flow in P group was decreased significantly. Serious renal
      and pancreatic damages were found in P group, the BUN and Cr levels were elevated
      significantly, and the ratio of TXA(2) to PGI(2) was increased at 2, 6 and 12 h.
      Compared with P group, the blood flow of kidney was elevated significantly at 6
      and 12 h after induction of ANP, the renal and pancreatic damages were
      attenuated, and the BUN and Cr levels were decreased significantly, and the ratio
      of TXA(2) to PGI(2) was decreased at 6 and 12 h in T group. CONCLUSION:
      Microcirculatory disorder (MCD) is an important factor for renal injury in ANP.
      Ligustrazine can ameliorate the condition of MCD and the damage of pancreas and
      kidney.

PMID- 17171805
TI  - Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor
      genes in a family with multiple cases of idiopathic bile acid malabsorption.
AB  - The etiology of most cases of idiopathic bile acid malabsorption (IBAM) is
      unknown. In this study, a Swedish family with bile acid malabsorption in three
      consecutive generations was screened for mutations in the ileal apical sodium
      bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for
      several of the nuclear receptors known to be important for ASBT expression: the
      farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha
      (PPARalpha). The patients presented with a clinical history of idiopathic chronic
      watery diarrhea, which was responsive to cholestyramine treatment and consistent
      with IBAM. Bile acid absorption was determined using (75)Se-homocholic acid
      taurine (SeHCAT); bile acid synthesis was estimated by measuring the plasma
      levels of 7alpha-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and PPARalpha
      genes in the affected and unaffected family members were analyzed using single
      stranded conformation polymorphism (SSCP), denaturing HPLC, and direct
      sequencing. No ASBT mutations were identified and the ASBT gene did not segregate
      with the bile acid malabsorption phenotype. Similarly, no mutations or
      polymorphisms were identified in the FXR or PPARalpha genes associated with the
      bile acid malabsorption phenotype. These studies indicate that the intestinal
      bile acid malabsorption in these patients cannot be attributed to defects in
      ASBT. In the absence of apparent ileal disease, alternative explanations such as
      accelerated transit through the small intestine may be responsible for the IBAM.

PMID- 17171806
TI  - Alpha-fetoprotein-producing colon cancer with atypical bulky lymph node
      metastasis.
AB  - Alpha-fetoprotein (AFP)-producing colorectal cancer is extremely rarely reported
      until now. All of the reported cases harboring synchronous hematogenous spread
      including liver and/or lung metastasis had a poor prognosis and died within 12
      mo. We here describe a 71-year old man with AFP-producing colon cancer who
      presented with an unusual bulky lymph node metastasis instead of hematogenous
      spread. He underwent adjuvant chemotherapy in addition to curative surgical
      resection, which prolonged his survival.

PMID- 17171807
TI  - Laparoscopic cholecystectomy in a patient with situs inversus totalis.
AB  - Currently, laparoscopic cholecystectomy is an undoubtfully optimal treatment of
      cholelithiasis. What about performing this procedure on a patient with situs
      inversus totalis and what are the difficulties of this operation for a right
      handed surgeon? We presented a 35-year-old man with unknown situs inversus
      totalis who was admitted with epigastric pain and digestive problems.
      Ultrasonography and computed tomography of the abdomen confirmed the diagnosis of
      a gallstone. Besides, the liver and gallbladder were on the left side and the
      spleen was on the right. All systems were left-right reversal as mirror image in
      all diagnostic studies. Laparoscopic cholecystectomy was safely performed,
      despite of difficulties of situs inversus. The patient was discharged on
      postoperative day 1. It should be considered that existence of other anomalies
      may easily cause uninvited injuries. In the patients with situs inversus,
      laparoscopic cholecystectomy can be safely managed by an experienced surgeon
      through laparoscopy, and also hepatobiliary surgery.

PMID- 17171808
TI  - Factors predicting suicide among Russians in Estonia in comparison with
      Estonians: case-control study.
AB  - AIM: To explore differences between suicide victims among Russian immigrants in
      Estonia and native Estonians, according to socio-demographic background,
      substance use pattern, and recent life events to find out immigration-specific
      factors predicting suicide. METHODS: The psychological autopsy study included 427
      people who committed suicide in 1999 and 427 randomly selected controls matched
      by region, gender, age, and nationality. RESULTS: The only variable that differed
      significantly between Russian and Estonian suicide cases was substance use
      pattern. Logistic regression models showed that factors associated with suicide
      for both nationalities were substance dependence and abuse (Russians: odds ratio
      [OR], 12.9; 95% confidence interval [95% CI], 4.2-39.2; Estonians: OR, 8.1; 95%
      CI, 3.9-16.4), economical inactivity (Russians: OR 5.5; 95% CI, 1.3-22.9;
      Estonians: OR, 3.1; 95% CI, 1.3-7.1), and recent family discord (Russians: OR,
      3.2; 95% CI, 1.1-9.9; Estonians: OR, 4.5; 95%, CI, 2.1-9.8). The variables that
      remained significant in the final model were having no partner (Estonians: OR,
      3.0; 95% CI, 1.6-5.5), being unemployed (Estonians: OR, 5.5; 95% CI, 2.0-15.4),
      and being an abstainer (Estonians: OR, 6.7; 95% CI, 2.5-17.6) for Estonians, and
      somatic illness (Russians: OR, 4.1; 95% CI, 1.4-11.7), separation (Russians: OR,
      32.3; 95% CI, 2.9-364.1), and death of a close person (Russians: OR, 0.2; 95% CI,
      0.04-0.7) for Russians. CONCLUSION: Although the predicting factors of suicide
      were similar among the Estonian Russians and Estonians, there were still some
      differences in the nature of recent life events. Higher suicide rate among
      Estonian Russians in 1999 could be at least partly attributable to their higher
      substance consumption.

PMID- 17171809
TI  - By the way, doctor. I'd like to keep the tanned look I got during summer
      vacation. Are self-tanning lotions and sprays a good idea? Are they safe to use?

PMID- 17171810
TI  - Abstracts of the American Society of Hematology 48th Annual Meeting, December 9
      12, 2006, Orlando, Florida, USA.

PMID- 17171811
TI  - Retraction notice to "The yeast RAD2, but not RAD1, gene is involved in the
      transcription-coupled repair of thymine glycols" [Mutat. Res. 337 (1995) 169
      178].

PMID- 17171812
TI  - [HIV infection course without antiretroviral treatment in South Africa].

PMID- 17171813
TI  - Terlipressin. Type I hepatorenal syndrome: an extra window of time before liver
      transplantation.
AB  - In some patients with type I hepatorenal syndrome, a retrospective study
      suggests, albeit with a low level of evidence, that terlipressin increases
      survival time by about a week, which sometimes allows enough time to find a
      suitable liver donor. Adverse effects due to the vasoconstrictive action of
      terlipressin require close monitoring during treatment.

PMID- 17171814
TI  - Fluoxetine. Bulimia nervosa: don't use.
AB  - In practice, in patients seeking treatment for bulimia nervosa, fluoxetine has
      been shown to provide only transient efficacy, and patients are exposed to the
      drug's adverse effects. Cognitive and behavioural therapies are better treatment
      options.

PMID- 17171815
TI  - Notice of withdrawal.

PMID- 17171816
TI  - Promethazine and sudden infant death.

PMID- 17171817
TI  - Melatonin and sleep disorders: no better than placebo.

PMID- 17171818
TI  - DNA repair by ERCC1 in non-small-cell lung cancer.

PMID- 17171819
TI  - Cytokine storm and an anti-CD28 monoclonal antibody.

PMID- 17171820
TI  - Cytokine storm and an anti-CD28 monoclonal antibody.

PMID- 17171821
TI  - Cytokine storm and an anti-CD28 monoclonal antibody.

PMID- 17171822
TI  - The state of primary care.

PMID- 17171823
TI  - The state of primary care.

PMID- 17171824
TI  - The state of primary care.

PMID- 17171825
TI  - Molecular epidemiology: HIV-1 and HCV sequences from Libyan outbreak.
AB  - In 1998, outbreaks of human immunodeficiency virus type 1 (HIV-1) and hepatitis C
      virus (HCV) infection were reported in children attending Al-Fateh Hospital in
      Benghazi, Libya. Here we use molecular phylogenetic techniques to analyse new
      virus sequences from these outbreaks. We find that the HIV-1 and HCV strains were
      already circulating and prevalent in this hospital and its environs before the
      arrival in March 1998 of the foreign medical staff (five Bulgarian nurses and a
      Palestinian doctor) who stand accused of transmitting the HIV strain to the
      children.

PMID- 17171826
TI  - The state of primary care.

PMID- 17171827
TI  - Neuromuscular denervation: Bax up against the wall in amyotrophic lateral
      sclerosis.

PMID- 17171828
TI  - Learning on the Web. Case 9: a mother's heartache.
AB  - A 35 year old white woman presented with chest pain and breathlessness 10 days
      following an elective caesarean section. This was her second pregnancy, which had
      proceeded to term without complications. Up until then, she had been completely
      fit and well. Her ECGs were found to be abnormal, and the ultrasound study of her
      heart gave serious cause for concern. This interactive case report charts the
      evolution of the patient's clinical course and provides concise and up-to-date
      literature reviews on two cardiac conditions that share a predilection for women
      in the peripartum period.

PMID- 17171829
TI  - Optic neuritis and bitemporal hemianopsia associated with isoniazid treatment in
      end-stage renal failure.

PMID- 17171830
TI  - Multidrug-resistant tuberculosis in Mumbai: it's only getting worse.

PMID- 17171831
TI  - Re: Triphasic waves versus nonconvulsive status epilepticus: EEG distinction. Can
      J Neurol Sci 2006;33:175-80.

PMID- 17171832
TI  - [Pain lasting 13 years].

PMID- 17171834
TI  - Vinorelbine: friend or foe?

PMID- 17171833
TI  - [Blood pressure lowering through physical training--what can be achieved?].
AB  - In the meantime, the positive effect of physical training, both in primary and
      secondary prevention of hypertension, has been confirmed in numerous studies. In
      recent years, it has been shown that regular sports activity of moderate
      intensity suffices to bring about a lowering of blood pressure. Highly
      recommended forms of training include walking, jogging, cycling and dynamic power
      training. Over a period of three to four months,a gradual increase in activity-
      for example, a daily training period of 15 to 20 minutes--should be the aim.
      However, an intensification of general physical activities may also lower blood
      pressure, irrespective of other risk factors.

PMID- 17171835
TI  - Managing managed health care.

PMID- 17171836
TI  - Hydatid disease - the 'water lily' sign.

PMID- 17171837
TI  - Vulvar cancer in HIV-positive young females.

PMID- 17171838
TI  - A giant abdominal mass and the master of disguise - what would Hamilton Bailey
      have said?

PMID- 17171839
TI  - [Pathology of the cerebellopontine angle].
AB  - The pathology of the cistern of the cerebellopontine angle is primarily that of
      the nervous and vascular structures that it contains and of the meninges that
      line it. Knowledge of its anatomy makes it possible to understand and search for
      a rare pathology, the hemifacial spasm, due to a conflict between the facial
      nerve and the vertebral artery and the posterior inferior cerbellerar artery.
      However, the pathology of the cerebellopontine angle remains especially tumoral.
      Imaging should not only make the diagnosis but also make an exhaustive,
      pretherapy, and accurate assessment of the three main tumours found in this area:
      the vestibular schwannoma, the meningioma, and the epidermoid cyst.

PMID- 17171840
TI  - Laterality of seizure onset and the simple reaction time: revamping the
      Poffenberger's paradigm for seizure surgery.
AB  - BACKGROUND: Crossed-uncrossed differentials (CUDs) are viewed as surrogates for
      interhemispheric transfer time (IHTT). Not uncommonly CUDs assume statistically
      significant negative values (inverted CUDs). This raises doubts of the accepted
      interpretation of CUDs, i.e. intra- and inter-hemispheric routings of signals in
      uncrossed and crossed responses, respectively. METHOD: Based on the evidence
      supporting directionality in callosal traffic, data are provided indicating that
      callosal transfers exclusively involve non-dominant responses and such transfers
      are modality non-specific. The evidence also indicates that neural handedness
      corresponds to behavioral only in a statistical manner and the former remains
      unchanged regardless of the subject's life experience. RESULTS: The neurally
      dominant side is the side that is directly connected to the major hemisphere
      (command center). The connection of the non-dominant side to the command center
      is via the corpus callosum; therefore, a delay occurs in the reaction time of all
      non-dominant effectors, corresponding to IHTT. Accordingly, negative CUDs
      indicate a mismatch of neural and behavioral (avowed) handedness of the subject.
      This group comprises a minority of 15-20% of the population. CONCLUSION:
      Comparing the response time of symmetrically located effector is a robust way of
      lateralizing a person's major hemisphere. The latter is also the site of
      initiation of seizures, as the minor hemisphere is bereft of independent motor
      activity. Sensory signals arising from the nondominant side of the body traverse
      the callosum before reaching the major hemisphere. Searching for ipsilateral
      somatosensory evoked potentials provides another approach in lateralizing the non
      dominant side of the body (ipsilateral to the major hemisphere). Practical uses
      of a conceptually revamped Poffenberger paradigm in neurosurgery are briefly
      reviewed.

PMID- 17171841
TI  - [Study on root fracture and alveolar bone absorption of doweled lower premolars].
AB  - PURPOSE: The aim of this study was to examine root fractures in the doweled lower
      premolars and their relationship to alveolar bone absorption on the buccal aspect
      of the abutment teeth. METHODS: Experiment 1. Fractures in the roots of the
      abutment teeth and absorption of the surrounding alveolar bone was visualized by
      Multi-image Micro CT (3DX) in nine lower premolar abutment teeth that had lost
      both their posts and their. Experiment 2. The stresses in the teeth were analyzed
      using a three-dimensional finite element model, both models with and without
      alveolar bone absorption, as determined from Experiment 1. The stress
      distributions of von Mises equivalent stress and the shear stresses in the XZ, YZ
      and XY direct ions were examined. RESULTS: Experiment 1. The absorption of the
      alveolar bone was observed on the buccal side, and the fractures in the roots
      were observed in the lingual to buccal direction. Experiment 2. In the case
      without alveolar bone absorption, the XY shear stress in the root for mesial or
      distal loads was concentrated near the cervix with a positive stress value, and
      close to the end of the post with a negative stress value. In the alveolar bone
      absorption model, the XY shear stress in the root for mesial or distal loads was
      concentrated close to the end of the post on the lingual side with a positive
      stress value and on the buccal side with a negative stress value. CONCLUSION: In
      the case without alveolar bone absorption, on stress concentration was observed
      at the end of the post. Otherwise, based on the results of the finite element
      model analysis, for mesial or distal loads, the root fracture in the abutment
      teeth would be considered to be caused by absorption of the alveolar bone and the
      buccal aspect.

PMID- 17171842
TI  - [Combination of asthma and COPD--more common than assumed?].

PMID- 17171843
TI  - [Interdental papilla reconstruction with prosthodontic treatment of maxillary
      central incisor: case report].
AB  - PATIENT: A 20-year-old female whose chief complaint was esthetic disturbance of a
      crown placed on the maxillary left central incisor. DISCUSSION: The interdental
      papilla was reconstructed only by the prosthodontic treatment of maxillary left
      central incisor. This case suggests that the proximal and subgingival contours of
      provisional crown is very important to the reconstruction of interdental papilla,
      and also suggests that the transmission of the information regarding the
      configuration of a provisional crown to the lab side is very important.
      CONCLUSION: This case shows that the emergence profile of a single crown,
      especially of its proximal aspect, is important to reconstruct the interdental
      papilla.

PMID- 17171844
TI  - [Case in which periodontal surgery was performed and prostheses were designed to
      match condylar movement].
AB  - PATIENT: A patient presented with malocclusion caused by generalized periodontal
      disease, subgingival caries, and poorly designed restorations and prostheses.
      Occlusal reconstruction was carried out in this case according to occlusal
      guidance that was determined based on mandibular head movement, following
      periodontal surgery. The emergence profile of the prostheses was made to match
      the periodontium. DISCUSSION: By achieving an occlusal form, where the maxillary
      and mandibular molar teeth could be instantly separated through proper anterior
      guidance corresponding to the internal structure of the mandibular joint, it was
      possible to attain long-term stability while maintaining harmony with the
      temporomandibular joint without damaging the periodontium. CONCLUSION: Occlusal
      guidance corresponding to the internal structure of the temporomandibular joint
      is important for maintaining the stability of the periodontium, teeth and
      temporomandibular joint.

PMID- 17171845
TI  - A 37-year-old man with a febrile illness. Staphylococcal toxic shock syndrome.

PMID- 17171847
TI  - Clarification of registration requirements for individual practitioners. Final
      rule.
AB  - The Drug Enforcement Administration (DEA) is amending its registration
      regulations to make it clear that when an individual practitioner practices in
      more than one State, he or she must obtain a separate DEA registration for each
      State. This amendment will make it easier for practitioners to understand the
      requirements of the Controlled Substances Act and its implementing regulations.

PMID- 17171846
TI  - Effect of diode laser irradiation on the apical sealing of MTA retrofillings.
AB  - Apical sealing is essential for the success of paraendodontic surgery, so any
      procedure that may favor an adequate sealing of the apical remainder should be
      performed. The purpose of this study was to evaluate the influence of diode laser
      irradiation on the apical sealing of root-end cavities with MTA retrofillings.
      Root canals in twenty extracted human teeth were shaped with K-files and filled
      with gutta-percha. The apexes were cut off and root-end preparations were
      performed. The roots were divided randomly in 2 groups. Group 1 (ten specimens)
      was retrofilled with MTA. Group 2 was irradiated with diode laser, with 1 W for
      20 seconds, on the apical surface and root end cavity before retrofilling with
      MTA. The specimens had their external surfaces impermeabilized with
      cyanoacrylate, except for the apical surface, and were then immersed in 1%
      rhodamine B dye for 72 h and placed in plaster stone. After that, the specimens
      were submitted to longitudinal abrasion until half of the root remained. The
      linear dye leakage was observed in these mid-roots between the root canal wall
      and retrofilling. The linear dye leakage was measured with Image Lab software,
      and the results were statistically analyzed with Student's t test. There were no
      statistically significant differences between the two groups (p > 0.05). The
      diode laser irradiation did not improve the apical sealing of MTA retrofillings
      under the conditions of this in vitro study.

PMID- 17171848
TI  - [Structural-logical educational technologies in secondary medical education].

PMID- 17171849
TI  - [Comment on "Pathogenesis of severe sepsis--from macrocirculation to
      mitochondria" by R. Kula et al].

PMID- 17171850
TI  - Medicare program; revisions to payment policies, five-year review of work
      relative value units, changes to the practice expense methodology under the
      physician fee schedule, and other changes to payment under part B; revisions to
      the payment policies of ambulance services under the fee schedule for ambulance
      services; and ambulance inflation factor update for CY 2007. Final rule with
      comment period.
AB  - This final rule with comment period addresses certain provisions of the Deficit
      Reduction Act of 2005, as well as making other changes to Medicare Part B payment
      policy. These changes are intended to ensure that our payment systems are updated
      to reflect changes in medical practice and the relative value of services. This
      final rule with comment period also discusses geographic practice cost indices
      (GPCI) changes; requests for additions to the list of telehealth services;
      payment for covered outpatient drugs and biologicals; payment for renal dialysis
      services; policies related to private contracts and opt-out; policies related to
      bone mass measurement (BMM) services, independent diagnostic testing facilities
      (IDTFs), the physician self-referral prohibition; laboratory billing for the
      technical component (TC) of physician pathology services; the clinical laboratory
      fee schedule; certification of advanced practice nurses; health information
      technology, the health care information transparency initiative; updates the list
      of certain services subject to the physician self-referral prohibitions,
      finalizes ASP reporting requirements, and codifies Medicare's longstanding policy
      that payment of bad debts associated with services paid under a fee
      schedule/charge-based system are not allowable. We are also finalizing the
      calendar year (CY) 2006 interim RVUs and are issuing interim RVUs for new and
      revised procedure codes for CY 2007. In addition, this rule includes revisions to
      payment policies under the fee schedule for ambulance services and the ambulance
      inflation factor update for CY 2007. As required by the statute, we are
      announcing that the physician fee schedule update for CY 2007 is -5.0 percent,
      the initial estimate for the sustainable growth rate for CY 2007 is 2.0 percent
      and the CF for CY 2007 is $35.9848.

PMID- 17171851
TI  - Pandemic unpreparedness?
AB  - Analysis of national influenza pandemic preparedness plans reveals that the
      preparations for an effective response in the early stages of a pandemic, while a
      vaccine is still being prepared, are giving cause for concern.

PMID- 17171852
TI  - Ocean's elevenses.

PMID- 17171853
TI  - Medicare and Medicaid programs; programs of all-inclusive care for the elderly
      (PACE); program revisions. Final rule.
AB  - This rule finalizes the interim final rule with comment period published in the
      Federal Register November 24, 1999 (64 FR 66234) and the interim final rule with
      comment period published in the Federal Register on October 1, 2002 (67 FR
      61496). The November 1999 interim final rule implemented sections 4801 through
      4803 of the Balanced Budget Act of 1997 (Pub. L. 105-33) and established
      requirements for Programs of All-inclusive Care for the Elderly (PACE) under the
      Medicare and Medicaid programs. The interim final rule with comment period
      published on October 1, 2002 (67 FR 61496) implemented section 903 of the
      Medicare, Medicaid, and SCHIP Benefits Improvement and Protection Act of 2000
      (BIPA) (Pub. L. 106-554).

PMID- 17171854
TI  - Medicare and Medicaid programs; hospital conditions of participation: patients'
      rights. Final rule.
AB  - This final rule finalizes the Patients' Rights Condition of Participation (CoP)
      which is applicable to all Medicare- and Medicaid-participating hospitals and
      contains standards that ensure minimum protections of each patient's physical and
      emotional health and safety. It responds to comments on the following standards
      presented in the July 2, 1999 interim final rule: Notice of rights; exercise of
      rights; privacy and safety; confidentiality of patient records; restraint for
      acute medical and surgical care; and seclusion and restraints for behavior
      management. As a result of comments received, we have revised the standards
      regarding restraint and seclusion and set forth standards regarding staff
      training and death reporting.

PMID- 17171855
TI  - [Obstructive sleep apnea syndrome and heart rhythm disturbances].
AB  - Review of terminology, predisposing factors, clinical signs and complications of
      the obstructive sleep apnea syndrome is presented. Main emphasis is made on heart
      rhythm disturbances in this disease. Possible causes of cardiac arrhythmias,
      special characteristics of their course in patients with severe concomitant
      pathology, methods of diagnosis and treatment, including the use of noninvasive
      positive pressure ventilation are discussed.

PMID- 17171856
TI  - [Is primary prevention of arterial hypertension with drugs possible? Results of
      the TROPHY Study].

PMID- 17171857
TI  - [Computed tomography of coronary arteries].
AB  - The review covers possibilities of modern techniques of computer tomography (CT)
      of coronary arteries: electron beam tomography and 4-, 16-, 64-slice multi-spiral
      CT. Main studies conducted in this area are analyzed. Results of these studies
      (values of sensitivity and specificity, numbers of included patients, numbers of
      segments of coronary arteries which were excluded from analysis because of poor
      quality of images) are presented and compared. Problems of further development of
      CT of coronary arteries are also considered.

PMID- 17171858
TI  - [Combination therapy in contemporary strategy of treatment of arterial
      hypertension. Review of data on efficacy and safety of fixed combination
      valsartan and hydrochlorothiazide].

PMID- 17171859
TI  - The role of atrial natriuretic peptide in cardiac surgery.

PMID- 17171860
TI  - Atrial natriuretic peptide plasma levels during cardiac surgery.
AB  - In this investigation, the hypothesis was tested that patients with valvular
      heart disease have higher atrial natriuretic peptide (ANP) plasma levels than
      patients with coronary artery disease during cardiac surgery. Six patients
      scheduled for valve replacement (group V) and seven scheduled for coronary artery
      bypass grafting (CABG) (group C) were studied. ANP plasma levels and hemodynamic
      measurements were obtained at several times during surgery. ANP levels were
      elevated in both groups compared to those measured in healthy volunteers; and ANP
      levels in valvular patients were found to be higher than in the CABG patients. In
      addition, isotonic fluid loading, rewarming during cardiopulmonary bypass, and
      weaning from cardiopulmonary bypass increased ANP from baseline in group C. Mean
      arterial pressure and ANP levels correlated in group C. Ejection fraction,
      pulmonary artery diastolic pressure, and right atrial pressure did not correlate
      with ANP levels in either group. In conclusion, patients with valvular heart
      disease have higher ANP levels during surgery compared to patients with coronary
      artery disease. This difference probably relates to different pressure and volume
      loads on atrial tissue.

PMID- 17171861
TI  - The effects of cardiopulmonary bypass on plasma concentrations and protein
      binding of methohexital and thiopental.
AB  - The effects of cardiopulmonary bypass (CPB) on plasma concentrations and protein
      binding of methohexital and thiopental were studied during continuous infusions
      in two groups of ten cardiac surgical patients. Patients were administered an
      infusion regimen designed to produce a stable total plasma concentration at 5
      mg/L for methohexital and 10 mg/L for thiopental. Prior to the commencement of
      CPB the mean (+/-SD) total plasma methohexital concentration was 5.00 +/- 0.69
      mg/L. This fell to 3.12 +/- 0.89 mg/L at two minutes after commencement of CPB,
      and rose to 4.67 +/- 1.11 mg/L by 75 minutes after commencement of CPB. The
      unbound fraction rose from 27.1 +/- 5.1% to 42.8 +/- 9.2% at five minutes after
      the start of CPB, and gradually decreased to 32.1 +/- 4.9% by 75 minutes. The
      unbound concentration (1.37 +/- 0.32 mg/L) was unaffected by the onset of CPB,
      being 1.51 +/- 0.49 mg/L at 75 minutes after the start of CPB. Thiopental
      followed a similar pattern to methohexital, with the total plasma thiopental
      concentration falling from 9.22 +/- 0.73 mg/L to 4.90 +/- 0.83 mg/L at two
      minutes after commencement of CPB, and rising again to 7.13 +/- 1.03 mg/L 75
      minutes later. During the same period the unbound fraction of thiopental rose
      from 16.1 +/- 2.5% to 30.3 +/- 7.3% five minutes after the start of CPB, and fell
      gradually to 22.8 +/- 5.8% after 75 minutes. The unbound concentration (1.51 +/-
      0.21 mg/L) was again unchanged by the onset of CPB, being 1.71 +/- 0.29 mg/L at
      75 minutes. Plasma protein binding of both drugs correlated strongly with plasma
      albumin concentration, which decreased by 40% during CPB. It is concluded that
      hemodilution caused the reduction in total drug concentration and protein binding
      at the onset of CPB, but that the decrease in protein binding counteracted the
      dilution of unbound drug, resulting in a stable unbound concentration throughout
      CPB, and that this effect may be common for barbiturates.

PMID- 17171862
TI  - Compartmental analysis of lidocaine kinetics during extracorporeal circulation.
AB  - The aim of this study was to measure the effects of extracorporeal circulation
      (ECC) on lidocaine disposition and to determine if therapeutic concentrations
      were achieved during ECC. Anesthesia was obtained by administration of fentanyl
      (50 microg/kg plus 0.3 microg/kg/min) and pancuronium bromide (0.1 mg/kg) along
      with controlled ventilation (10 mL/kg, PaCO2, 30 to 34 mmHg). Lidocaine was
      administered to ten patients in bolus doses of 2 mg/kg at the time of
      endotracheal intubation and during ECC at aortic declamping. Samples were
      collected at 20 and 40 seconds, and at 1, 3, 5, 10, 15, 20, 25, and 30 minutes
      after drug administration. Blood sampling was arterial during anesthesia
      induction and from the oxygenator during ECC. Blood levels of lidocaine were
      determined by the immunofluorescence method. The kinetic studies of lidocaine
      showed increases in plasma volume and in the volume of the peripheral
      compartment, along with decreased volume in the compartment of well-perfused
      tissues during ECC. The fraction of the dose of lidocaine administered during ECC
      behaved accordingly, showing a decrease in the quantity of drug in the well
      perfused tissues, and an increase in the other two compartments when compared to
      values before ECC. The doses administered gave plasma concentrations of 1.55
      microg/mL, which are considered therapeutic. Thus, it is not recommended to
      increase the lidocaine dosage during ECC.

PMID- 17171863
TI  - Comparative hemodynamic effects of propofol and thiamylal sodium during
      anesthetic induction for myocardial revascularization.
AB  - The safety and efficacy of propofol, a new intravenous anesthetic agent, have
      been demonstrated in healthy patients. Twenty-one patients, ASA III-IV,
      undergoing elective myocardial revascularization, were randomly chosen to receive
      either propofol, 2.5 mg/kg, or thiamylal, 4 mg/kg. for the induction of
      anesthesia. Hemodynamics were recorded at one and three minutes after drug
      administration during spontaneous respiration. After the addition of halothane
      and pancuronium with controlled ventilation, measurements were made immediately
      prior to and one minute after intubation. Five patients were dropped from the
      study, four due to airway problems and one due to severe hypotension following an
      induction dose of propofol. Statistics were done using data from the remaining 16
      patients, eight in each group. Administration of propofol resulted in significant
      decreases in mean arterial pressure (MAP), systemic vascular resistance (SVR),
      and left ventricular stroke work index (LVSWI); as well as an increase in heart
      rate (HR). These changes were further accentuated by the addition of halothane
      and pancuronium prior to intubation. Patients in the thiamylal group experienced
      no significant hemodynamic changes until halothane and pancuronium were added and
      controlled ventilation was instituted. With these additions, the thiamylal group
      showed significant decreases in MAP and LVSWI immediately prior to intubation.
      Both groups experienced significant increases in HR following intubation, but no
      evidence of myocardial ischemia was seen in either group. All other parameters
      returned toward control values. Propofol appeared to be safe and effective for
      the induction of anesthesia in this group of patients, although its hemodynamic
      effects were greater than those of thiamylal.

PMID- 17171864
TI  - Evaluation of a new design pulmonary artery catheter for intraoperative
      ventricular pacing.
AB  - A new design pulmonary artery catheter and pacing probe were evaluated in 30
      patients undergoing cardiac surgery. Ventricular pacing was attempted before,
      during, and after cardiopulmonary bypass. Ventricular current threshold, output,
      resistance, and R wave sensitivity were measured during all three periods.
      Successful pacing was achieved in 69 of 72 attempts, the vast majority completed
      in less than four minutes. Pacing thresholds and R wave sensitivities were within
      acceptable ranges and compatible with commercial pulse generators. Ventricular
      pacing can be quickly and reliably established with this type of pacing pulmonary
      artery catheter. The results suggest this system can be used to effect cardiac
      pacing in the patient requiring emergency extrinsic pacemaker support.

PMID- 17171865
TI  - Local anesthesia for radial artery cannulation: a comparison of a lidocaine
      prilocaine emulsion and lidocaine infiltration.
AB  - A topical anesthetic emulsion consisting of a mixture of lidocaine and prilocaine
      (EMLA) was used in an attempt to reduce the pain associated with radial artery
      cannulation. Three groups were compared: (1) EMLA applied at least 90 minutes
      prior to cannulation (EMLA 90); (2) EMLA applied 60 minutes prior to cannulation
      (EMLA 60); and (3) lidocaine 2% infiltration performed immediately prior to the
      procedure (infiltration). Pain was registered using visual analog and verbal
      ranking scales by both the patient and an independent observer. The EMLA 90 group
      experienced significantly less pain (P < .001) than either the EMLA 60 or
      lidocaine infiltration groups. There was no statistically significant difference
      in pain scores between the EMLA 60 and infiltration groups. Local side-effects of
      EMLA were negligible.

PMID- 17171866
TI  - Transcutaneous monitors during one-lung ventilation: are they reliable?
AB  - During one-lung ventilation, levels of oxygen and carbon dioxide in the blood are
      commonly assessed by intermittent blood gas sampling. Transcutaneous PO2 (tcPO2)
      and transcutaneous PCO2 (tcPCO2) have been reported to accurately reflect
      arterial PO2 (PaO2) and arterial PCO2 (PaCO2) in hemodynamically stable patients.
      Transcutaneous monitors appear to be ideal for detecting trends toward hypoxia
      and hypercarbia, conditions that may not be evident when using intermittent blood
      gas sampling, while pulse oximetry, since it reflects saturation, may not detect
      hypoxia until it has already occurred. Thirty: one patients undergoing one-lung
      ventilation were monitored using both transcutaneous electrodes applied to the
      upper arm (group 1) or chest (group 2) and arterial blood gas sampling. Arterial
      blood gases were sampled while tcPO2 and tcPCO2 values were being recorded.
      Regression, correlation, and covariance analyses were performed. Correlation
      coefficients of PaO2 to tcPO2 varied from .05 to .99 for each patient. The slopes
      of individual regression lines varied from 0.03 to 1.16. Correlation coefficients
      of PaCO2 to tcPCO2 varied from .01 to .99, while the slopes of individual
      regression lines ranged from 0.02 to 5.89. Covariance analyses revealed
      considerable variation in PaO2 to tcPO2 and PaCO2 to tcPCO2 in individual
      patients even under stable hemodynamic conditions. Analysis of covariance also
      demonstrated that in group 2 the slopes comparing arterial and transcutaneous
      values were significantly different for PaO2 <100 mmHg and PaO2 >200 mmHg. In
      group 1, for PaO2 <100 mmHg, there was no difference in slopes but y-intercepts
      were significantly different (P < .05). However, transcutaneous indices were
      significantly different in both groups for PaO2 <100 mmHg and PaO2 >200 mmHg. It
      is concluded that transcutaneous monitoring is useful to indicate trends in
      arterial values in some patients, but blood gas analysis is still necessary to
      verify the reliability of such monitoring.

PMID- 17171867
TI  - Thermodilution cardiac output measurements during conventional and high-frequency
      ventilation.
AB  - The thermodilution method for cardiac output determinations correlates well with
      Fick and dye dilution methods. Experimental work with thermodilution techniques
      has shown that individual measurements of right heart cardiac output during
      conventional ventilation vary throughout the respiratory cycle. The aims of this
      study were to compare thermodilution cardiac output determinations made at a
      fixed point (zero end-expiratory pressure [ZEEP]) with those made randomly
      throughout the respiratory cycle during conventional controlled positive pressure
      ventilation (CPPV) and high-frequency jet ventilation (HFJV) with up to 10 cm H2O
      positive endexpiratory pressure (PEEP). There were no statistically significant
      differences between the cardiac output determinations made at ZEEP and randomly
      in the ventilation cycle in any group and all correlations were significant. The
      clinical implications of these results are discussed, and it is concluded that it
      is not necessary to time the measurements of thermodilution cardiac output
      determinations during CPPV or HFJV with up to 10 cm H2O of PEEP.

PMID- 17171868
TI  - Effect of hypothermia on median nerve somatosensory evoked potentials.
AB  - Median nerve somatosensory evoked potentials (SEP) were monitored in ten patients
      undergoing cardiac surgery with hypothermic cardiopulmonary bypass (CPB).
      Anesthesia was induced and maintained with sufentanil, oxygen, and pancuronium.
      Esophageal, nasopharyngeal, rectal, and blood temperatures were continuously
      monitored. SEPs were recorded before induction of anesthesia, after induction,
      and during cooling and rewarming on CPB. There was a strong negative correlation
      between SEP latencies and temperature (except rectal) (r = -.91, P < .001). for
      cortical latency and esophageal temperature. A decrease in esophageal temperature
      of 1 degrees C resulted in an increase in SEP latency of 1 ms. There was also a
      weak positive correlation between evoked potential amplitude and temperature (r =
      .19) for cortical amplitude and esophageal temperature.

PMID- 17171869
TI  - Preservation of the ischemic canine myocardium: a comparison of hypothermia,
      lidoflazine, and ketanserin.
AB  - The purpose of this study was to determine whether ketanserin protects the
      globally ischemic canine heart and whether such protection, if present, is
      independent of that provided by hypothermia or calcium channel blockade with
      lidoflazine. Forty mongrel dogs, anesthetized with halothane, were divided into
      eight groups of five and subjected to one hour of global myocardial ischemia
      during hypothermic (30 degrees C; groups 1 to 4) or normothermic (37 degrees C;
      groups 5 to 8) cardiopulmonary bypass (CPB). Dogs in groups 1 and 5 served as
      controls with respect to prebypass myocardial protective therapy, and received
      only placebo (a normal saline bolus) prior to CPB. Before bypass, dogs in groups
      2 and 6 received lidoflazine, 1.25 mg/kg intravenously (IV); those in groups 3
      and 7 received ketanserin, 5 mg IV bolus, followed by a continuous infusion at 33
      microg/min during bypass. Animals in groups 4 and 8 were given both lidoflazine
      and ketanserin according to the dosing schedules above. No type of pharmacologic
      or mechanical cardiovascular support was provided after termination of CPB.
      Postbypass hemodynamic performance and survival of the unsupported animal were
      assumed to reflect the degree of myocardial protection during CPB. One minute
      after bypass, mean arterial pressure and cardiac output were decreased in all
      groups. Cardiac output was lower in groups 5 to 8 (normothermic CPB) than in
      groups 1 to 4 (hypothermic CPB). After CPB, left ventricular filling pressures
      were elevated in all groups kept normothermic and in group 3 (hypothermic CPB
      plus ketanserin). By 15 minutes after CPB, there were no survivors in groups 5,
      7, and 8. Sixty percent of animals in group 6 (normothermic CPB plus lidoflazine)
      survived to the end of the study. Relative odds of survival were increased 110
      fold by hypothermia and sevenfold by lidoflazine. Conversely, treatment with
      ketanserin was associated with an increased likelihood of nonsurvival. It is
      concluded that, at the doses studied, ketanserin does not protect the canine
      myocardium against ischemic injury and may exert a detrimental effect when
      combined with calcium channel blockade in this setting.

PMID- 17171870
TI  - Lactate extraction and myocardial damage after countershock at different energy
      levels.
AB  - The relationship between myocardial lactate metabolism and the energy dose of
      direct countershock was studied in 15 dogs anesthetized with halothane. Five dogs
      received two shocks of 5 joules delivered energy each, five animals received two
      shocks of 10 joules delivered energy each, and five dogs received two shocks of
      20 joules delivered energy each. All animals had positive myocardial lactate
      extraction in the baseline state (5 joules, 38% +/- 23.7 (SD); 10 joules, 59.6%
      +/- 11.4; 20 joules, 38% +/- 11.1). Lactate extraction after countershock
      progressively decreased with increasing energy dose and then returned to
      baseline. The maximal reduction in percent lactate extraction increased with
      increasing energy dose (5 joules, 13.9% +/- 16.1; 10 joules, 33% +/- 37; 20
      joules, 30.5% +/- 37.5) and seemed to reach a threshold below which no further
      decrease occurred. Myocardial damage, as measured by a damage index derived from
      myocardial uptake of technetium-99 pyrophosphate, increased steadily with
      increasing energy dose (2.0 +/- 2.5 with 5-joule shocks; 38 +/- 32 with 10
      joules; and 99 +/- 70 with 20 joules). These results show a consistent reduction
      in aerobic metabolism immediately following electric countershock. Even at low
      energy doses, myocardial lactate extraction showed a detectable decrease and at
      higher energies approached net lactate production. Reductions of global lactate
      extraction did not completely predict the amount of myocardial damage. Localized
      measures of anaerobic metabolism or mitochondrial function might provide a better
      correlation with localized damage.

PMID- 17171871
TI  - Cardiac electrophysiologic interactions of bepridil, a new calcium antagonist,
      with enflurane, halothane, and isoflurane.
AB  - Bepridil is an investigational calcium antagonist that also has fast sodium
      channel blocking and antidysrhythmic properties. In the present study, the
      potential interactions of bepridil with volatile anesthetics on cardiac
      electrophysiologic parameters were evaluated in open-chest dogs. Twenty-four dogs
      anesthetized with enflurane (n=6), halothane (n=6), isoflurane (n=6), or
      chloralose (n=6) received 2.5 mg/kg of bepridil intravenously (IV). Twenty-five
      additional dogs anesthetized with enflurane (n=7), halothane (n=6), isoflurane
      (n=6), or chloralose (n=6), received bepridil, 5.0 mg/kg, IV. Dogs anesthetized
      with cloralose served as controls. Cardiac electrophysiologic parameters were
      measured after the dogs were anesthetized and were repeated 5, 15, 30, 45, and 60
      minutes after bepridil infusion. Plasma bepridil concentrations were also
      determined at the above time points. Synergy between bepridil and enflurane was
      demonstrated in the following cardiac electrophysiologic parameters: depression
      of sinus node function as evidenced by severe depression of sinus node
      automaticity and conduction; depression of atrioventricular function as evidenced
      by prolongation of the atrial-His bundle interval and the Wenckebach R-R
      interval; and, prolongation of the atrial effective refractory period. No synergy
      was demonstrated between bepridil and halothane or isoflurane when compared to
      bepridil's effects during chloralose anesthesia. It is concluded that significant
      synergistic cardiac electrophysiologic effects exist between bepridil and
      enflurane in dogs. It is recommended that caution be used when anesthetizing
      patients receiving bepridil with enflurane until human data on the use of this
      combination of pharmacologic agents is available.

PMID- 17171872
TI  - Esophageal stethoscope loss complicating transesophageal echocardiography.

PMID- 17171873
TI  - Mitral valve replacement complicated by endobronchial hemorrhage: spontaneous,
      traumatic, or iatrogenic?

PMID- 17171875
TI  - The intra-aortic balloon pump: a review.
AB  - Intra-aortic balloon pump therapy is often life-saving in patients with
      refractory cardiac failure following cardiopulmonary bypass, in the peri-infarct
      period, or in treating complications of coronary artery angioplasty.
      Anesthesiologists are intimately involved in the care of the majority of IABP
      patients and require a thorough understanding of the equipment, its physiologic
      effects, and potential complications.

PMID- 17171874
TI  - Dantrolene-induced hyperkalemia in a patient treated with diltiazem and
      metoprolol.

PMID- 17171876
TI  - A 66-year-old man has an unexpected low cardiac output syndrome during repeat
      myocardial revascularization.

PMID- 17171877
TI  - Pro: Barbiturates should be used for brain protection during open heart surgery.

PMID- 17171878
TI  - Con: Barbiturates for brain protection during cardiopulmonary bypass: fact or
      fantasy?

PMID- 17171879
TI  - The Seldinger technique.

PMID- 17171880
TI  - High-frequency ventilation with the Bennett MA-1 for respiratory support in
      patients with septic ARDS.

PMID- 17171881
TI  - Improving the design and function of double-lumen tubes.

PMID- 17171882
TI  - Right upper lobe obstruction with right-sided double-lumen endobronchial tubes: a
      comparison of two tube types.
AB  - Twenty-nine patients undergoing left thoracotomy consecutively were intubated
      with right-sided double-lumen endotracheal tubes in the conventional "blind"
      fashion. The first 20 received Leyland red-rubber double-lumen tubes, and the
      subsequent nine received Mallinckrodt polyvinylchloride double-lumen tubes. The
      patency of the right upper lobe bronchial orifice was then assessed by flexible
      fiberoptic bronchoscopy. Right upper lobe obstruction occurred in 89% of the
      polyvinylchloride tube intubations and in 10% of the red-rubber tube intubations.

PMID- 17171883
TI  - Continuous low-flow supracarinal and subcarinal oxygen insufflation in addition
      to intermittent positive-pressure ventilation does not improve gas exchange.
AB  - Recent studies in animals have demonstrated that continuous insufflation of
      oxygen near the tracheal carina results in ventilation and carbon dioxide removal
      that is proportional to the flow rate. The purpose of this study was to determine
      whether the addition of supracarinal and subcarinal low-flow oxygen insufflation
      to conventional intermittent positive-pressure ventilation (IPPV) of critically
      ill and anesthetized patients results in increased ventilation and improved
      oxygenation. In eight studies a supracarinal catheter (3.7 mm OD) was placed 1 to
      2 cm above the carina, and in another eight studies two subcarinal catheters (1.7
      mm OD) were placed 2 cm below the tracheal carina under direct vision with a
      fiberoptic bronchoscope. Both supracarinal and subcarinal catheters were passed
      within the lumen of an 8 mm ID endotracheal tube. In both groups, conventional
      IPPV consisted of a tidal volume of 10-12 mL/kg, respiratory rate of 8 to 10
      breaths/min, 0 cm H2O positive end-expiratory pressure (PEEP), and F1O2 of 1.0.
      In both groups, continuous oxygen insufflation flow rates were 0.05, 0.10, and
      0.20 L/ kg/min. It was found that compared with control conditions (no
      insufflation), oxygen insufflation at all flow rates in both supracarinal and
      subcarinal insufflation groups did not cause any significant change in either
      oxygenation or ventilation. There was a significant increase in proximal peak
      airway pressure with each incremental increase in continuous oxygen flow rate.
      Conversely, there was a significant decrease in mean arterial pressure and
      cardiac output with each incremental increase in continuous oxygen flow rate. It
      is concluded that use of continuous low-flow insufflation of oxygen with simple
      administration systems (catheters within the lumen of endotracheal tube) in
      addition to conventional IPPV is contraindicated at the present time. Further
      studies using different insufflation systems may prove to be worthwhile.

PMID- 17171884
TI  - Prebypass hemodynamic stability of sufentanil-O2, fentanyl-O2, and morphine-O2
      anesthesia during cardiac surgery: a comparison of cardiovascular profiles.
AB  - Cardiovascular responses and the need for intervention with vasoactive agents
      were measured prospectively in a randomized study of 50 adult patients receiving
      sufentanil (n = 20), fentanyl (n = 20), or morphine (n = 10) anesthesia for
      cardiac surgery. Measurements were recorded and compared during induction and
      prebypass at intervals during which airway or surgically induced stress responses
      were likely to be greatest. Randomized, double-blinded doses of opioids were
      administered slowly and titrated according to clinical responses (hemodynamics)
      and the electroencephalogram. Mean doses were as follows: from induction until
      time of incision, sufentanil, 9.1 microg/kg; fentanyl, 58 microg/kg; and
      morphine, 2.5 mg/kg; and total dose for surgery; sufentanil, 18.9 microg/kg;
      fentanyl, 95.4 microg/kg; and morphine, 4.4 mg/kg. Equi-anesthetic depth in
      patients receiving sufentanil or fentanyl was confirmed by continuous
      electroencephalographic monitoring. Patients anesthetized with sufentanil and
      fentanyl showed marked cardiovascular stability and rarely responded to stimuli.
      Systolic arterial pressure, mean arterial pressure, heart rate, cardiac index,
      systemic vascular resistance index, pulmonary vascular resistance index, stroke
      volume index, and stroke work index values were similar in the two groups.
      Patients receiving morphine experienced large changes in several variables.
      Pharmacologic intervention was made when systolic arterial pressure deviated more
      than 30% from pre-event values and was uncontrolled by additional opioids.
      Interventions were necessary more often in patients receiving morphine (nine of
      ten) or fentanyl (12 of 20) than in patients receiving sufentanil (six of 20), P
      < 0.05. Results from this study suggest that morphine is a relatively
      unsatisfactory anesthetic, while sufentanil and fentanyl, at equi-anesthetic
      depths, provide stable and satisfactory hemodynamics.

PMID- 17171885
TI  - Influence of high-dose opioid anesthesia on posterior tibial nerve somatosensory
      cortical evoked potentials: effects of fentanyl, sufentanil, and alfentanil.
AB  - The effects of high doses of fentanyl (group F), sufentanil (group S), and
      alfentanil (group A) on posterior tibial nerve somatosensory cortical evoked
      potentials were studied in 30 patients scheduled for elective valve replacement
      surgery. Anesthesia was induced with either fentanyl, 75 microg/kg, sufentanil, 5
      microg/kg, or alfentanil, 125 microg/kg. The lungs were ventilated with
      oxygen/air. A bolus dose of fentanyl, 25 microg/kg, was given 30 minutes after
      induction of anesthesia in group F. Anesthesia was maintained with a continuous
      infusion of sufentanil, 5 microg/kg/h, in group S, or alfentanil, 500
      microg/kg/h, in group A. Latencies of the peaks of the primary cortical complex
      (P1, N1, P2) increased by 1 to 2 ms after induction of anesthesia, although this
      was significant (P < 0.01) only for P1 and N1 in groups F and S. N2 latency
      increased significantly (P < 0.01) by 6 to 10 ms in all groups. P1-N1 amplitude
      did not change after induction of anesthesia. N1-P2 amplitude decreased
      significantly (P < 0.01) to 60%-70% of preinduction values in groups F and S. P2
      N2 amplitude decreased significantly (P < 0.01) to 60%-70% of preinduction values
      in all groups. P1, N1 and P2 latencies did not change significantly from the post
      induction values in the period preceding cardiopulmonary bypass (75 +/- 16
      minutes) in groups F and S. In group A significant changes were observed only for
      N1 and P2 latency (P < 0.01). During this period there was a further gradual
      increase in N2 latency and amplitudes remained stable, except P1-N1 amplitude in
      group F, which decreased significantly (P < 0.05). A bolus dose of fentanyl, 25
      microg/kg, given in group F at 30 minutes after induction of anesthesia did not
      change latencies and amplitudes. No significant differences in latency or
      amplitude were found at any time among the three study groups. It is concluded
      that anesthesia with high doses of fentanyl, sufentanil, or alfentanil is a
      suitable technique when intraoperative monitoring of posterior tibial nerve
      somatosensory cortical evoked potentials is indicated.

PMID- 17171886
TI  - Influence of acute preoperative hemodilution on right ventricular function.
AB  - In a randomized study, the effects of acute, preoperative hemodilution (HD) (12
      mL/kg) on right ventricular function were investigated in coronary artery surgery
      patients with reduced left ventricular function (ejection fraction < 50%) and
      significant stenosis of the right coronary artery (RCA). Blood was replaced
      either by hydroxyethyl starch (HES) solution (ratio 1:1; HD-HES; n = 15) or by
      Ringer's lactate, (RL) (ratio 2.5:1; HD-RL; n = 15). Fifteen comparable patients
      without HD served as a control group. Besides commonly measured pressure
      parameters, right ventricular end-diastolic volume (RVEDV), right ventricular end
      systolic volume (RVESV), and right ventricular ejection fraction (RVEF) were
      measured using a computerized thermodilution technique before and after HD, as
      well as after extracorporeal circulation (ECC). Right ventricular systolic
      function, expressed as RVEF, was not changed significantly by HD in any group.
      Furthermore, right ventricular function of the hemodiluted patients was not
      impaired by the subsequent ECC procedure. None of the traditionally measured
      parameters could be correlated significantly to the right ventricular
      thermodilution variables. It is concluded that moderate HD does not change right
      ventricular function even when the RCA is significantly stenosed.

PMID- 17171887
TI  - Regional hemodynamics and oxygen supply during isovolemic hemodilution in the
      absence and presence of high-grade beta-adrenergic blockade.
AB  - Studies were performed in 16 pentobarbital-anesthetized dogs to evaluate regional
      circulatory effects of isovolemic hemodilution in the absence (group 1) and
      presence (group 2) of high-grade beta-adrenergic blockade with propranolol.
      Regional blood flow measured with 15 microm radioactive microspheres was used to
      calculate regional oxygen supply. In group 1, hemodilution with 5% dextran
      (40,000 molecular weight) reduced arterial hematocrit and oxygen content by
      approximately one half and had heterogeneous effects on regional blood flows.
      Blood flow was unchanged in the renal cortex, liver, and spleen, and it increased
      in the pancreas, duodenum, brain, and myocardium; however, only in the brain and
      myocardium were increases in blood flow sufficient to maintain oxygen supply at
      baseline (pre-hemodilution) levels. In group 2, intravenous administration of
      propranolol (1 mg/kg) itself decreased blood flow in the spleen and myocardium
      and had no other regional effects. Hemodilution after propranolol caused regional
      circulatory changes that were essentially similar to those in the absence of
      propranolol. It is concluded that (1) during isovolemic hemodilution, oxygen
      supply to the brain and myocardium is maintained at the expense of oxygen supply
      to less critical organs, and (2) this pattern of regional circulatory response
      during hemodilution remains intact in the presence of high-grade beta-adrenergic
      blockade with propranolol.

PMID- 17171888
TI  - Steroids protect the beta-adrenergic system during reperfusion after ischemia:
      effects of methylprednisolone on the beta-adrenergic response system.
AB  - Methylprednisolone sodium succinate (MPSS) administered during reperfusion may
      improve myocardial function. These effects have been related to adrenergic
      stimulation. The present study investigated (1) the effects of ischemia and
      reperfusion on the beta-adrenergic response system and (2) the ability of MPSS to
      modify the ischemic effects on the beta-adrenergic system. Isolated perfused rat
      hearts were used. The ischemic protocol consisted of aerobic perfusion (20
      minutes) followed by total, global normothermic (37 degrees C) ischemia (30
      minutes) and reperfusion (30 minutes) with MPSS (0, 100, 500, or 1,000 mg/L). The
      non-ischemic protocol consisted of aerobic perfusion (20 minutes) followed by
      aerobic perfusion (20 minutes) with MPSS (0, 100, 500, or 1,000 mg/L). At the end
      of the experiments all hearts were rapidly frozen in liquid nitrogen. Crude
      sarcolemmal membranes were prepared and stimulated at the beta-receptor, at the
      coupling (G.- or N-) protein, or directly at the adenylate cyclase enzyme (AC).
      Results were assessed by cyclic adenosine monophosphate (cAMP) production. Tissue
      specimens were analyzed for myocardial content of cAMP and methylprednisolone
      (MP). In the ischemic protocol, the responsiveness of the beta-adrenergic system
      was significantly reduced at the G.-protein level. The treatment with MPSS (100
      or 500 mg/L) during reperfusion preserved the beta-adrenergic response. MPSS
      (1,000 mg/L) offered no protection. In the non-ischemic protocol, MPSS reduced
      the response of the beta-adrenergic system in a dose-dependent manner at the same
      level. The hearts in the ischemic protocol had significantly higher contents of
      MP than the hearts in the non-ischemic protocol at corresponding concentrations
      of MPSS. The present study suggests that postischemic cardiac failure may result
      in part from beta-adrenergic dysfunction. This loss of function, probably at the
      level of the protein connecting the receptor and AC, can successfully be
      prevented by an optimal dose of MPSS during reperfusion after ischemia.

PMID- 17171889
TI  - Reduction in mortality from cardiac causes in goldman class IV patients.
AB  - In 1977, Goldman et al evaluated cardiac patients for non-cardiac operations and
      showed a high incidence of cardiac death in high-risk cardiac patients (Goldman
      class IV). The present study was designed to prospectively evaluate the incidence
      of cardiac death as well as overall mortality in 49 patients belonging to Goldman
      class IV at the present time. Four patients of 49 (8.2%) died of cardiac causes,
      and seven other patients died of non-cardiac causes. Thus, the overall mortality
      rate was 22.4% (11/49). There has been a marked reduction in cardiac mortality
      from 56% in Goldman et al's 1977 data to 8.2% in the present data. All of the
      developments and advances in patient care over the past 10 years probably
      contributed to this reduction in mortality from cardiac causes.

PMID- 17171890
TI  - Comparison of superoxide dismutase, thiopental, and nimodipine for maintenance of
      somatosensory evoked responses during aortic cross-clamping and declamping in
      dogs.
AB  - Paraplegia is a potential complication of aortic cross-clamping. The occurrence
      of this devastating sequela has caused increased interest in the use of
      somatosensory evoked responses (SER) to monitor spinal cord ischemia during
      aortic cross-clamping. This study was designed to examine changes in SERs during
      clamping and declamping of the canine aorta after injection of superoxide
      dismutase (SOD), thiopental (T), and nimodipine (N). In the control group, cross
      clamping the aorta produced an increase in latency and a decrease in amplitude of
      the SER starting at two minutes. Isoelectric SERs were obtained after 16 minutes
      of aortic cross-clamping, but recovered with cross-clamp removal. When the aorta
      was clamped for more than 16 minutes in the control group, the isoelectric SERs
      obtained were irreversible. After the injection of SOD and T, SER latencies and
      amplitudes changed to a smaller degree with aortic cross-clamping and did not
      become isoelectric even after 20 minutes of clamping. During aortic cross-clamp
      removal in the control group, SERs initially improved and then showed signs of
      reperfusion ischemia, which disappeared after eight minutes. There were no
      significant SER changes due to reperfusion when SOD or T or the combination was
      given prior to aortic cross-clamping. There was no difference in SER changes from
      the control group during aortic cross-clamping and after release of cross
      clamping when N was given. Nimodipine did not alter SER changes from aortic cross
      clamping alone. In summary, SOD and T, alone or in combination, protect the
      spinal cord against ischemia during aortic cross-clamping and declamping.

PMID- 17171891
TI  - Oxygenator exhaust capnography: an in vitro evaluation.
AB  - The aim of the study was to examine whether oxygenator exhaust capnography could
      be used to monitor blood carbon dioxide tension in an in vitro cardiopulmonary
      bypass model. Carbon dioxide tension in the oxygenator's exhaust gas was measured
      by a capnograph and compared with that in the blood measured by blood gas
      analysis. Also investigated was the relationship between the capnograph's
      measurements and blood pH. The effects of gas and blood flow, temperature, and pH
      on the measurements were examined. A good correlation was found between PCO2
      measured by the capnograph and by the blood gas analyzer (r = 0.997, P < 0.001).
      When the capnograph's results were corrected for 95% oxygen, the accuracy
      improved further. There was a significant correlation between oxygenator exhaust
      PCO2 and temperature (rs = 0.843, P < 0.05), but the difference in PCO, was small
      in the range examined. No significant correlation was found between oxygenator
      exhaust PCO2 and blood or gas flow. A reasonable correlation between blood pH and
      oxygenator exhaust PCO2 (r = 0.965, P < 0.001) was found, but the metabolic
      component of pH could be altered without correlation with exhaust PCO2 (rs =
      0.203). In conclusion, oxygenator exhaust capnography was used with reasonable
      accuracy and reliability to monitor blood PCO2 in an in vitro cardiopulmonary
      bypass model.

PMID- 17171892
TI  - The current state of intraoperative echocardiography in North America: results of
      a survey.

PMID- 17171893
TI  - Intraoperative cardiac arrest caused by acute thrombosis of an aortic prosthetic
      valve.

PMID- 17171894
TI  - An unusual manifestation of pulmonary artery perforation during pulmonary artery
      catheter insertion.

PMID- 17171895
TI  - Anesthetic management for tracheal resection and reconstruction.

PMID- 17171896
TI  - Case conference. A 60-year-old black woman with a small cell carcinoma of the
      lung develops a superior vena cava syndrome.

PMID- 17171897
TI  - Pro: Benzodiazepines are contraindicated as induction agents for coronary artery
      surgery.

PMID- 17171898
TI  - Con: Benzodiazepines are not contraindicated as induction agents for coronary
      artery surgery.

PMID- 17171899
TI  - Propofol for induction in cardiac patients.

PMID- 17171900
TI  - The use of external defibrillation pads in redo cardiac surgery.

PMID- 17171901
TI  - Processed EEG: a machine and a number are not enough.

PMID- 17171902
TI  - The incidence of prebypass dysrhythmias in patients undergoing coronary artery
      surgery.
AB  - The incidence of dysrhythmias during the prebypass period of coronary artery
      surgery has not been accurately reported. Using Holter monitoring of the
      electrocardiogram, this study was undertaken to determine the incidence of
      dysrhythmias and ischemia and their relationship to specific events during the
      prebypass period. The role of preoperative calcium entry blockers (CEB), beta
      adrenergic blockers (BB), or both on the incidence of dysrhythmias and ischemia
      was also studied. One hundred thirty-eight patients were premedicated with
      morphine, scopolamine, and diazepam. Anesthesia was induced with fentanyl or
      sufentanil followed by either pancuronium or vecuronium and maintained with
      sufentanil or enflurane. All 138 patients experienced a dysrhythmia during the
      prebypass period. Seventy-five percent of the patients had at least one episode
      of a supraventricular dysrhythmia (SVD), 39% had a sinus bradycardia, and 20% had
      a conduction abnormality. Ninety-two percent of the patients had premature
      ventricular contractions (PVC) and, surprisingly, 76% had non-sustained
      ventricular tachycardia. One patient developed ventricular fibrillation and one
      had ventricular tachycardia. The peak incidence of dysrhythmias occurred at
      insertion of the pulmonary artery (PA) catheter and at aortic dissection. The
      incidence of prebypass ischemia was 18%, but these patients did not have a higher
      incidence of ventricular dysrhythmias. Preoperative CEBs and BBs did not
      influence the incidence of ischemia or dysrhythmias with the exception of SVD;
      there was a significantly lower incidence at PA catheterization in patients
      taking CEBs preoperatively (P < .05). It can be concluded that dysrhythmias are
      very common during the prebypass period. The low rate of progression to life
      threatening dysrhythmias may be related to the fact that the majority occurred
      during mechanical stimulation and that patients were chronically taking CEBs
      and/or BBs preoperatively.

PMID- 17171903
TI  - Intravenous nifedipine for control of hypertension in patients after coronary
      artery bypass graft surgery.
AB  - A study was undertaken to assess the use of intravenous nifedipine in controlling
      hypertension in patients following coronary artery surgery. A combined
      hemodynamic and metabolic assessment was carried out in 15 patients on data
      recorded at six sequential time intervals: (1) baseline, (2) control of blood
      pressure, (3) 30 minutes after control of blood pressure, (4) 1.5 hours after
      control of blood pressure, (5) 3.5 hours after control of blood pressure, and (6)
      30 minutes after discontinuing nifedipine. Coronary sinus and great cardiac vein
      blood flows were measured by the continuous thermodilution technique using the
      Baim coronary sinus flow catheter. Intravenous nifedipine was run initially at an
      average rate of 1.82 microg/kg/min. It took an average time of 12 minutes to
      lower the blood pressure to less than 130 mmHg systolic. There were highly
      significant decreases in systolic, mean, and diastolic blood pressures (P <
      .001), associated with significant decreases in systemic vascular resistance (P <
      .001) and left ventricular stroke work index (P < .05). There was an increase in
      cardiac output at 30 and 90 minutes of infusion (P < .05), and the stroke volume
      was increased 90 minutes after starting nifedipine (P < .05). The increase in
      heart rate was not significant. There was no significant effect on conduction
      times as measured by PR and QRS intervals on the ECG. However, the QTc interval
      was decreased after 3.5 hours (P < .05). There was an increase in right atrial
      pressure at 90 minutes and again 30 minutes after stopping nifedipine. (P < .05).
      The pulmonary artery pressure also was increased after stopping the infusion (P <
      .05). The pulmonary capillary wedge pressure, pulmonary vascular resistance, and
      right ventricular stroke work index remained unchanged. Coronary sinus and great
      cardiac vein flows were maintained despite a decrease in perfusion pressure,
      suggesting that nifedipine is a potent coronary vasodilator. Indeed, coronary
      vascular resistance was significantly decreased (P < .05). Myocardial oxygen
      consumption remained unchanged. The lactate extraction indicated that myocardial
      metabolism remained aerobic regionally and globally. Thus, the results suggest
      that blood pressure was easy to control and that there were no adverse effects on
      atrioventricular conduction, cardiac performance, regional and global myocardial
      oxygen utilization, or lactate extraction.

PMID- 17171904
TI  - Revascularization of the right coronary artery: influence on thermodilution right
      ventricular ejection fraction.
AB  - This study was designed in order to evaluate the influence of right coronary
      artery (RCA) disease and its revascularization on right heart performance
      monitored by measuring thermodilution right ventricular ejection fraction (RVEF).
      Forty patients undergoing elective aortocoronary bypass surgery were divided into
      two groups: group 1, with RCA revascularization, n=20; and group 2, without RCA
      disease or revascularization, n=20. RVEF was measured using a pulmonary arterial
      catheter mounted with a fast-response thermistor and a bedside microprocessor
      ejection fraction computer. The major finding of the study was that myocardial
      revascularization with extracorporeal circulation was followed by a decrease in
      RVEF which was significantly more pronounced in group 1 (-13.1%) in comparison to
      group 2 (-5.0%). RVEF gradually increased after bypass, but did not reach
      baseline values. By the first postoperative day, RVEF had reached baseline values
      again in group 1 and had increased beyond baseline values in group 2.
      Traditionally measured hemodynamic parameters could not be correlated with the
      course of RVEF, except for cardiac index. The present study further suggests that
      right-sided events may have clinical effects on left-sided function. Inadequate
      protection of the right heart, especially in patients with RCA stenosis, may
      result in depression of right ventricular myocardial performance, which can be
      monitored serially by measuring RVEF.

PMID- 17171905
TI  - Comparison of the hemodynamic and echocardiographic effects of sufentanil,
      fentanyl, isoflurane, and halothane for pediatric cardiovascular surgery.
AB  - Sufentanil, fentanyl, halothane, and isoflurane were compared as sole anesthetic
      agents in 48 infants and children aged 6 months to 9 years, undergoing repair of
      congenital heart defects. Patients were randomly assigned to receive sufentanil,
      20 microg/kg, fentanyl, 100 microg/kg, isoflurane, 1.6%, or halothane, 0.9%,
      along with pancuronium, 0.08 mg/kg, for induction and maintenance of anesthesia.
      Cardiovascular function was measured by echocardiography prior to induction,
      postinduction, and postintubation. Systemic arterial pressure and heart rate were
      also recorded. Left ventricular ejection fraction (LVEF) decreased following
      induction with each agent: sufentanil 9%, fentanyl 9%, isoflurane 4%, and
      halothane 8%. Following intubation LVEF increased in the sufentanil, fentanyl,
      and isoflurane groups, but LVEF remained 13% below baseline values in the
      halothane group. Five of the 12 patients in the halothane group had a LVEF less
      than 55%. Arterial pressure immediately prior to bypass was significantly less
      than baseline in each group; however, arterial pressure was higher in the
      narcotic groups during isolation and cannulation of the great vessels. It is
      concluded that halothane, 0.9%, used as an induction agent in infants and
      children undergoing cardiac surgery causes a clinically significant decrease in
      LVEF. Based on the echocardiographic data, sufentanil, fentanyl, and isoflurane
      as used in the present study do not have a clinically significant effect on
      cardiac function and may offer an advantage to infants and children with marginal
      cardiovascular reserve.

PMID- 17171906
TI  - Creatine kinase activity and temperature in children after cardiac surgery.
AB  - The preoperative and postoperative serum creatine kinase (CK) activity and
      postoperative temperatures were studied in children undergoing surgery for
      congenital heart disease. Using multiple linear and logistic regression and
      analysis of variance, associations were found between postoperative CK activity
      (>2000 IU/L) and the use of succinylcholine, aortic cross-clamp time (>30
      minutes), cardiopulmonary bypass time (>60 minutes), the development of fever
      (>38.5 degrees C), and complications. Complications were defined as hemodynamic
      instability, poor peripheral perfusion, metabolic acidosis, and eventual multiple
      organ failure. Associations were also found between postoperative fever and the
      development of complications. The results suggest that children who develop serum
      CK elevations greater than 2000 IU/L and fever greater than 39.5 degrees C during
      the early postoperative period after cardiac surgery more often develop serious
      complications.

PMID- 17171907
TI  - Complement and leukocytes during cardiopulmonary bypass: effects on plasma C3d
      and C5a, leukocyte count, release of granulocyte elastase and granulocyte
      chemotaxis.
AB  - In an effort to further elucidate the complex changes in the complement-leukocyte
      system during cardiopulmonary bypass (CPB), plasma levels of C3d, C5a, and
      granulocyte elastase bound to alpha1-proteinase inhibitor (E-alpha1 PI) were
      followed prior to, during, and after CPB. Leukocyte and differential cell counts
      and granulocyte migration were also determined. Complement activation was
      documented during CPB by an increase in plasma C3d corrected for hemodilution.
      Significant amounts of C5a were not revealed. Cell counts decreased during CPB
      but, if corrected for hemodilution, remained unchanged apart from a slight
      decrease in lymphocyte count after 60 minutes. Eighteen hours after CPB,
      neutrocytosis and lymphopenia occurred. Plasma E-alpha1 PI increased during CPB,
      reflecting release of granulocyte lysosomal enzymes. Granulocyte migration was
      transitorily depressed during CPB, and it was shown that this was due to the
      appearance of an intrinsic cellular defect. CPB is associated with acute changes
      in cells and plasma, resembling an acute whole-body inflammatory response, with
      transitory impairment of granulocyte migration. The clinical significance of
      these observations remains to be determined.

PMID- 17171908
TI  - Hormonal effects of an induction dose of etomidate for patients undergoing urgent
      myocardial revascularization.
AB  - The use of etomidate for induction of anesthesia in patients requiring urgent
      coronary artery surgery provides good cardiovascular stability. However, long
      term etomidate infusions may cause transient signs of adrenocortical suppression.
      The purpose of this study was to determine whether an induction bolus dose of
      etomidate would cause clinically relevant endocrine dysfunction in urgent
      coronary artery bypass patients. With institutional review board approval, 11
      patients were prospectively randomized to a diazepam (control) or etomidate rapid
      sequence induction. The diazepam group (n=6; mean, 69 years) received 0.4 mg/kg
      of diazepam. The etomidate group (n=5; mean, 54 years) received 0.3 mg/kg of
      etomidate. Maintenance anesthesia included nitrous oxide, oxygen, pancuronium,
      and fentanyl in increments up to 32 microg/kg. Hemodynamics, cortisol,
      epinephrine, and norepinephrine were measured both intraoperatively and
      postoperatively. The only significant difference between the two groups in
      hemodynamic parameters was a higher heart rate in the etomidate group. Both
      agents adequately controlled the stress response to intubation as judged from the
      levels of epinephrine, norepinephrine. and cortisol. However, in both groups
      epinephrine and norepinephrine increased between intubation and removal of the
      aortic cross-clamp. Cortisol also increased from the time of cross-clamp removal
      to 12 and 24 hours post-bypass. During anesthesia and surgery in the pre-bypass
      period, there was a decrease in cortisol over time in the etomidate group, and
      there was an increase with diazepam. Thus, etomidate provided stable
      hemodynamics, possible mild intraoperative adrenocortical suppression, a
      depressed hormonal stress response to intubation, and a normal hormonal reaction
      to the later part of surgery and the postoperative period.

PMID- 17171910
TI  - Changes in the pulmonary capillary pressure after cardiac surgery.
AB  - The changes in the pulmonary circulation in 37 cardiac surgery patients
      undergoing coronary artery bypass (CABG), n=16; aortic valve replacement (AVR),
      n=13; and mitral valve replacement (MVR), n=8 were studied. The visual technique
      for the determination of pulmonary capillary pressure (Pc) was used in the
      preoperative and postoperative periods. The ratio of Pc to the pulmonary artery
      wedge pressure (Pw) was calculated to determine whether Pc and Pw varied
      independently. In addition, total pulmonary vascular resistance (PVR) was divided
      into precapillary (ra) and postcapillary (rv) components. Results from the CABG
      patients showed that the relationship between Pc and Pw remained constant despite
      an increased cardiac output. This differs from the data obtained from AVR and MVR
      patients in whom the Pc/Pw ratio was significantly higher after surgery.
      Therefore, Pw would underestimate Pc in this group of patients. In addition, MVR
      patients showed a significant postoperative increase in PVR and rv as compared
      with their preoperative values. This was also significantly higher than the rv in
      either AVR or CABG patients. The etiology of this change is unknown.

PMID- 17171909
TI  - A method of rapid-sequence induction using high-dose narcotics with vecuronium or
      vecuronium and pancuronium in patients with coronary artery disease.
AB  - A method of rapid-sequence induction was studied in 18 patients undergoing
      coronary artery bypass grafting (CABG) to assess the adequacy of relaxation for
      endotracheal intubation without resulting in major changes in heart rate (HR).
      Ten patients received vercuronium, 0.2 mg/kg (V); and eight patients received
      vecuronium, 0.1 mg/kg, and pancuronium, 0.1 mg/kg (V + P). All patients then
      received fentanyl, 50 to 70 microg/kg, or sufentanil, 5 to 7 microg/kg, followed
      60 seconds later by intubation. Patients were assessed for ulnar and mandibular
      nerve response to train-of-four (TOF) and tetanic (T) stimulation at 60 seconds;
      presence or absence of coughing or bucking; degree of vocal cord relaxation
      (1=none, 2=some, 3=complete relaxation); ability to intubate at 60 seconds; and
      changes in HR. At the time of intubation, 17 patients had four twitches to TOF
      and a positive response to T stimulation of the ulnar nerve, while all 18
      patients had zero or one twitch to TOF and only four had a positive response to T
      stimulation of the mandibular nerve (P < .0001 for T and TOF, ulnar v
      mandibular). Coughing and bucking were not observed in any patient. Vocal cord
      position was "3" in 14 patients and "2" in four patients. All patients were
      intubated without difficulty. The mean change in HR was -4.1 beats/min for
      patients receiving V and +16.4 beats/min for those receiving V + P (P < .002 for
      change in HR), with two V + P patients developing tachycardia. It is concluded
      that the onset of neuromuscular blockade is more rapid in the distribution of the
      mandibular nerve than at the ulnar nerve; mandibular nerve stimulation is a
      better predictor of adequate intubating conditions; good intubating conditions
      can be attained with either V or V + P; and, rapid-sequence induction with V is
      safe from a cardiac standpoint as measured by changes in HR, but the addition of
      pancuronium is unnecessary.

PMID- 17171911
TI  - Effects of the volatile anesthetic agents on sinus node function and
      atrioventricular conduction in dogs: a comparison with chloralose anesthesia.
AB  - The effects of equipotent concentrations (1.5 times minimum alveolar
      concentration) of the inhalational agents halothane, enflurane, and isoflurane on
      sinus node function, and atrioventricular (A-V) conduction and refractoriness
      were compared with chloralose anesthesia in 49 mongrel dogs. Sinus node function
      was assessed using corrected sinus node recovery time. Atrial-His and His
      ventricular conduction times were measured at paced heart rates of 150, 180, and
      200 beats/min, and A-V refractoriness was assessed by Wenckebach periodicity.
      There was no evidence that sinus node function was impaired by any of the
      inhalational agents. Enflurane anesthesia was associated with a significant
      prolongation of atrial-His conduction at paced heart rates of 180 and 200
      beats/min when compared to chloralose anesthesia and the other two inhalational
      agents (P < .001). Atrioventricular refractoriness was impaired by enflurane (P <
      .001) and halothane (P < .05), but not isoflurane, when compared with chloralose
      anesthesia. Ventricular-His conduction was not altered by any of the agents. The
      authors conclude that enflurane is associated with a greater impairment of A-V
      conduction and refractoriness than halothane or isoflurane, and that these
      changes are related to the anesthetic agent and not the anesthetic state.

PMID- 17171912
TI  - The effect of arterial pressure alterations during halothane anesthesia on
      residual flow and infarct size with transient regional ischemia of the dog.
AB  - The present study was designed to determine if infarct size under halothane
      anesthesia could be reduced by increasing the pressure gradient across the
      collateral vascular bed, thereby increasing flow within the occluded vascular
      bed. Forty-nine mongrel dogs were anesthetized with halothane under identical
      physiologic conditions with the exception of systemic arterial blood pressure.
      The control group of 18 animals anesthetized with halothane was compared to two
      experimental groups. In one group of 15 dogs, the mean systemic pressure was
      raised 25% above control with phenylephrine (BP25). In the second group of 15
      dogs, systemic pressure was raised 50% above control (BP50). Adjacent marginal
      branches of the left circumflex coronary artery were ligated for 90 minutes
      followed by 90 minutes of reflow. The area of the occluded vascular bed was
      similar in all groups, but the area of infarction as a percentage of the occluded
      vascular bed was reduced from 47.7 +/- 4.7% to 25.4 +/- 4.3% in the BP25 group (P
      < or = .05 v control) and to 33.1 +/- 5.0% in the BP50 group. Flow measurements
      using microspheres showed a larger zone of ischemic tissue receiving adequate
      residual flow in the BP25 and BP50 groups compared to the control. It is
      concluded that infarct size during halothane anesthesia in the dog can be reduced
      by increasing systemic blood pressure with phenylephrine.

PMID- 17171913
TI  - Intraoperative stroke during carotid endarterectomy without a change in the
      spectral edge frequency of the compressed spectral array.

PMID- 17171914
TI  - Atrial myxoma: case report, brief review, and recommendations for anesthetic
      management.

PMID- 17171916
TI  - Left ventricular free wall rupture in acute myocardial infarction--a spectrum of
      severity.

PMID- 17171915
TI  - Primary cardiac tumors: case presentations and anesthetic considerations for
      lesions other than classical benign myxomas.

PMID- 17171917
TI  - Right ventricular perforation in a patient with a pulmonary artery catheter.

PMID- 17171918
TI  - Protamine allergy.

PMID- 17171919
TI  - A 51-year-old man undergoing a redo-CABG develops ARDS and dies of Hypoxemia.

PMID- 17171920
TI  - Pro: Isoflurane is contraindicated for use in coronary artery surgery.

PMID- 17171921
TI  - Con: Isoflurane is contraindicated in patients with coronary artery disease.

PMID- 17171922
TI  - Amrinone, platelets, and the balloon pump.

PMID- 17171923
TI  - A modified setup for cardiac output determination in case of an inaccessible
      pulmonary artery catheter.

PMID- 17171924
TI  - Efficacy of enoximone in the management of refractory low-output states following
      cardiac surgery.
AB  - Fifteen consecutive patients with post-cardiac surgery low-output states
      refractory to catecholamine inotropic support and intra-aortic balloon counter
      pulsation (seven patients), were given enoximone (MDL 17,043, a phosphodiesterase
      inhibitor), 1 to 2 mg/kg, as a slow intravenous bolus injection, followed by a
      continuous infusion of 3 to 10 microg/kg/min. Enoximone resulted in a marked
      improvement in clinical and hemodynamic conditions. Despite the severity of their
      initial status, all the patients survived their acute circulatory failure and all
      but two were discharged from the hospital. Hemodynamic improvement was observed
      as early as 15 minutes after the drug administration and reflected the previously
      reported inotropic and vasodilatory properties of enoximone. No serious adverse
      effects were observed. Enoximone thus appears safe and effective in the
      management of post-cardiac surgery low-output states. Its effects are additive to
      those of high-dose catecholamines.

PMID- 17171925
TI  - Effects of high-dose fentanyl on fluid and vasopressor requirements after cardiac
      surgery.
AB  - The effects of two different anesthetic techniques on postoperative
      cardiopulmonary events, fluid and vasopressor requirements, and overall intensive
      care unit (ICU) course were studied in patients undergoing elective myocardial
      revascularization (CABG) (N = 20) or single cardiac valve replacement (N = 20).
      Patients were randomized to receive either high-dose fentanyl (F, 75 microg/kg
      followed by 0.3 microg/kg/min) or diazepam-ketamine (0.8 mg/kg D and 2 mg/kg K
      followed by 0.07 mg/kg/h D and 1 mg/kg/h K). No significant differences in
      preoperative demographics, prebypass hemodynamics, ischemic crossclamp, or total
      cardiopulmonary bypass times were noted. Patients receiving F had lower systemic
      arterial pressures and vascular resistances and required more vasopressors during
      the first 12 hours postoperatively. They also had a more positive cumulative
      fluid balance at 24 and 48 hours postoperatively, despite a higher incidence of
      postoperative diuretic use in CABG patients receiving F. Rectal temperature was
      significantly higher at four and eight hours postoperatively in F patients. Time
      until arousal and length of ICU stay were significantly greater with F, although
      duration of intubation did not differ between anesthetic techniques. Although the
      data does not provide an explanation for these differences, it indicates that
      these two techniques produce quite different physiologic responses in the
      postoperative period following cardiac surgery. In summary, it was found that F
      for cardiac surgery was accompanied by increased postoperative fluid and
      vasopressor requirements with increased Qsp/Qt and longer ICU stays compared to
      diazepam and ketamine. This study suggests that some anesthetic techniques may
      provide less complicated and less costly postoperative courses than others, with
      the same outcome after cardiac surgery. Information on the postoperative effects
      of long-acting anesthetic agents is sparse and more studies of these effects and
      their mechanisms are necessary because they may affect patient management after
      cardiac surgery.

PMID- 17171926
TI  - Sternal retraction and pulmonary artery catheter compromise.
AB  - Forty-one consecutive open-chest cardiac procedures requiring sternal retractors
      for visualization were prospectively studied. Chest x-rays demonstrating the
      course of the introducer sheaths and pulmonary artery catheters (PACs) were taken
      before and after sternal retractor expansion. Five different introducer sheath
      insertion sites were monitored (right internal jugular, left internal jugular,
      left subclavian, right subclavian, and right supraclavicular). The incidence of
      permanent loss of pulmonary artery (PA) and central venous pressure (CVP)
      waveforms was recorded after retractor expansion. Forty-five percent of both the
      left and right subclavian groups suffered loss of the PA and CVP waveforms,
      whereas none of the other insertion site groups was affected. Therefore, it is
      recommended that PACs inserted for surgery requiring sternal retractors be placed
      via nonsubclavian routes.

PMID- 17171927
TI  - Clinical evaluation of the edwards laboratories and oximetrix mixed venous oxygen
      saturation catheters.
AB  - Mixed venous oxygen saturation is continuously monitored during and following
      cardiac operations in many institutions. Important therapeutic decisions may
      depend on the values indicated by the instrument. The accuracy of the system used
      is therefore of critical importance. Twenty-seven patients scheduled for coronary
      artery bypass surgery were monitored with either an American Edwards Laboratories
      (Irvine, CA) or Oximetrix, Inc (Mountain View, CA) fiberoptic pulmonary artery
      catheter. After preinsertion calibration, the values measured by the instruments
      were compared to blood samples analyzed with an Instrumentation Laboratories IL
      282 cooximeter at eight intervals. It was found that under these clinical
      conditions there was significantly less difference in the values measured with
      the Oximetrix catheter v those determined with the IL 282 co-oximeter as compared
      with the values measured with the American Edwards catheter v the IL 282 co
      oximeter. The percentage difference in oxygen saturation (ie, error) measured
      with the Edwards Laboratories catheter increased over time, averaging more than
      7.5% at the last three data points.

PMID- 17171928
TI  - Anomalous left coronary artery arising from the pulmonary artery: a series of 27
      infants undergoing operation in the first years of life.
AB  - Between 1977 and 1987, 27 infants (aged 3 to 54 months) underwent surgical
      treatment for correction of an anomalous left coronary artery arising from the
      pulmonary artery (ALCAPA). All had a direct aortic reimplantation. The overall
      operative mortality was 18.5% (five deaths). The follow-up period was from 2
      months to 8 years (mean, 38 months). No late deaths occurred. During the 10
      years, modifications of the surgical procedure and myocardial preservation were
      introduced (ie, complete resection of the pulmonary trunk made anastomosis
      easier; since 1982, cardioplegia in both coronary systems has been used, and left
      atrial-to-aortic assistance was introduced). The latter was carried out when
      surgical repair was associated with acute cardiac failure and a high left atrial
      filling pressure at the end of cardiopulmonary bypass. In view of the results
      during the latter part of this series, it is felt that surgery should not be
      restricted in younger patients (< 12 months). If medical treatment is
      unsuccessful, surgery aims to avoid irreversible left ventricular dysfunction and
      development of severe endocardial fibroelastosis.

PMID- 17171929
TI  - Superoxide dismutase and hemodynamic changes following aortic crossclamp release.
AB  - Release of an aortic crossclamp usually results in hypotension which is mainly
      due to hypovolemia from sequestration of fluid in the tissues and the release of
      vasoactive substances (ie, bradykinin, free radicals) that increase capillary
      permeability. The purpose of this study was to evaluate superoxide dismutase
      (SOD), a free-radical scavenger, as a pharmacologic technique to prevent
      hemodynamic changes following aortic crossclamping and release. Fourteen mongrel
      dogs were studied and divided into two groups. The aorta was clamped for 60
      minutes. Group A received NaHCO3, 3.5 mEq/kg, and SOD, 15,000 U/kg; while group B
      received only NaHCO3, 3.5 mEq/kg, prior to aortic crossclamp release. There was a
      statistically significant difference in cardiac output, systolic blood pressure,
      systemic and pulmonary vascular resistances, and arterial oxygen tension between
      the two groups following aortic crossclamp release. Cardiac output increased from
      2.2 +/- .05 to 2.5 +/- .03 L/min (P < .05) after declamping, and returned toward
      preclamping baseline values after five minutes in group A. In group B, cardiac
      output decreased from 2.3 +/- .05 to 2.1 +/- .01 (P < .005) after declamping and
      remained unchanged five minutes later. No statistically significant changes in
      PaO2 occurred in group A, while there was a significant decrease in PaO2 in group
      B after crossclamp release. In group B, PaO2 decreased from 95 +/- 7 to 70 +/- 1
      mmHg (P < .005) after crossclamp release. Bradykinin levels were almost identical
      in both groups studied. It is concluded that SOD significantly decreases the
      cardiovascular changes following aortic crossclamp release.

PMID- 17171930
TI  - Reversal of the adverse cardiovascular effects of intravenous diltiazem in
      anesthetized dogs.
AB  - Intravenous diltiazem can be used to treat myocardial ischemia, hypertension, and
      supraventricular dysrhythmias, but significant adverse effects including
      atrioventricular block and hypotension have been reported. At the present time,
      there is controversy as to which drug is most effective in reversing these
      sequelae. This study was designed to assess the effectiveness of calcium chloride
      v epinephrine in reversing these side effects. The hemodynamic and
      electrophysiologic effects of diltiazem infusion were investigated in eight dogs
      anesthetized with fentanyl and nitrous oxide/oxygen. This study confirmed that
      diltiazem infusions in high concentrations produced predominantly
      atrioventricular conduction depression followed by profound hypotension.
      Epinephrine infusion proved to be most effective in attenuating and eliminating
      each of these deleterious side effects. In contrast, calcium chloride did not
      significantly increase heart rate or blood pressure or reverse atrioventricular
      block. In two instances calcium chloride produced further depression of
      atrioventricular conduction, leading to severe bradycardia and sinus arrest.
      Although calcium chloride increased left ventricular contractile force (LV dP/
      dt) and cardiac index (CI), mean arterial pressure was not affected and SVR was
      further decreased. This study indicates that calcium chloride should not be given
      to reverse the side effects of diltiazem in the presence of atrioventricular
      conduction block or profound hypotension. Calcium chloride is indicated only when
      isolated myocardial depression is present and after the calcium channels have
      been reopened by epinephrine.

PMID- 17171931
TI  - Myocardial recovery from the cardiac depressant effects of enflurane and
      halothane.
AB  - Recovery from the cardiac depressant effects of enflurane and halothane was
      examined in the dog heart-lung preparation (HLP) and in right ventricular muscle
      isolated from guinea pig hearts. In the HLP. recovery was studied under two
      conditions: (1) After a two-hour exposure to anesthetic concentrations increasing
      from 0.36 to 1.2 MAC, and (2) after a one-hour exposure to a single concentration
      that raised the left atrial pressure (LAP) to 9 to 10 mmHg. Under either
      condition, +dP/dtmax. was significantly less depressed with enflurane and
      returned to preanesthetic control levels, while recovery with halothane remained
      significantly below control. Following the longer exposure. recovery of the LAP
      and left ventricular function curves (LVFC) was significantly less with
      halothane; however, this difference was not observed after the shorter exposure
      period. In electrically paced, isometrically contracting right ventricular strips
      exposed for one hour to 2.25 vol% enflurane (a concentration that reduced
      contractility by 45%), force development returned within 60 minutes to values
      above preanesthetic control values. After an identical depression for one hour
      with halothane (0.80 vol%), force development recovered to values less than those
      observed following enflurane. These data indicate that the recovery from
      anesthetic-induced negative inotropic effects in isolated cardiac preparations is
      better with enflurane than halothane.

PMID- 17171932
TI  - Physiologic and histologic determinants of gas exchange during induction of oleic
      acid pulmonary edema.
AB  - Five anesthetized mongrel dogs were studied during the induction of acute oleic
      acid pulmonary edema to determine the influence of cardiac output (Qt),
      extravascular lung water (ETV), and the degree of alveolar flooding on pulmonary
      gas exchange. Ot and ETV were measured by thermal dye dilution techniques,
      alveolar flooding was assesed by histologic studies, and gas exchange was
      quantitated by the multiple inert gas elimination technique (MIGET). Estimates of
      the inert gas venous admixture [(Qva/ Qt) IG%] were obtained at different
      experimental stages from the MIGET data to provide an index of overall gas
      exchange impairment. Pulmonary edema was produced by the intravenous (IV)
      infusion of oleic acid (0.08 mL/kg). Measurements of Qt, ETV and (Qva/Qt) IG%
      were made prior to lung injury and at 40, 80, and 120 minutes after injury. After
      death the lungs were inflated and frozen. Thirty cores of lung parenchyma (2 mL
      each) were obtained for histologic assessment of alveolar flooding. In the early
      phase of edema formation (0 to 80 minutes), (Ova/Qt) IG% increased as ETV
      increased. After 80 minutes, ETV stabilized and further changes in (Qva/ Qt) IG%
      were then primarily determined by changes in Qt (r = .94). The histologically
      assessed degree of alveolar flooding correlated well with ETV at the 120-minutes
      stage (r = .85). However, by use of multivariate analysis, the addition of the
      histologic information did not appreciably improve the prediction of gas exchange
      in acute oleic acid pulmonary edema.

PMID- 17171933
TI  - The effects of metabolic acidosis and alkalosis on the response to
      sympathomimetic drugs in dogs.
AB  - Sympathomimetic drugs are commonly used in many circumstances to increase cardiac
      output, blood pressure, and myocardial contractility. However, factors such as
      acidosis or alkalosis are known to influence the action of these drugs. This
      study looked at the response to the administration of epinephrine,
      norepinephrine, dopamine, dobutamine, isoproterenol, and glucagon at normal pH
      and under acidotic (pH 7.2 +/- 0.01) and alkalotic (pH 7.59 +/- 0.01) conditions
      in 17 dogs. Acidosis was produced with an infusion of hydrochloric acid and
      alkalosis by infusion of sodium bicarbonate. The infusions were given over one
      hour followed by a 15- to 30-minute stabilization period. With the administration
      of each sympathomimetic drug at each pH level, hemodynamic parameters and
      measurements of myocardia; contractility were recorded. Epinephrine increased
      cardiac output at normal pH, but decreased cardiac output under conditions of
      both acidosis and alkalosis; the net change from values at pH 7.40 was nearly 3
      L/min. The only other drug to demonstrate this reversal of cardiac output, though
      to a lesser degree, was dopamine, 10 microg/kg/min, and only in the alkalotic
      state. Dobutamine was the only drug that decreased contractility under acidotic
      conditions, while all other drugs caused an increase. In sum, epinephrine was the
      only drug markedly affected by metabolic acidosis and alkalosis. Isoproterenol's
      hemodynamic effects were altered the least by changes in acid-base balance.
      Alkalosis had an equally adverse effect on the cardiovascular system as compared
      with acidosis.

PMID- 17171934
TI  - Arteriovenous fistula following percutaneous internal jugular vein cannulation: a
      report of carotid artery-to-internal jugular vein fistula.

PMID- 17171935
TI  - Perioperative alcohol withdrawal syndrome associated with a myocardial
      revascularization procedure.

PMID- 17171936
TI  - Protamine-induced hypotension in a two-year-old child.

PMID- 17171938
TI  - Cardiac transplantation: a surgical perspective.

PMID- 17171937
TI  - Medical aspects of cardiac transplantation.

PMID- 17171939
TI  - Anesthetic considerations for patients undergoing cardiac transplantation.

PMID- 17171940
TI  - Intensive care of the cardiac transplant recipient.

PMID- 17171941
TI  - Case conference. A 44-year-old attorney was transferred from another hospital in
      cardiogenic shock for transplant evaluation.

PMID- 17171942
TI  - Pro: Calcium salts are contraindicated in the weaning of patients from
      cardiopulmonary bypass.

PMID- 17171943
TI  - Con: Calcium salts are contraindicated in weaning of patients from
      cardiopulmonary bypass after coronary artery surgery.

PMID- 17171944
TI  - Thermodilution cardiac output provides unanticipated intraoperative diagnosis.

PMID- 17171945
TI  - Thermodilution cardiac output provides unanticipated intraoperative diagnosis.

PMID- 17171946
TI  - Cardiac output: measurement of the future or relic of the past?

PMID- 17171947
TI  - Simultaneous measurements of cardiac output by thermodilution, esophageal
      Doppler, and electrical impedance in anesthetized patients.
AB  - Simultaneous intraoperative measurements of cardiac output were obtained in nine
      patients with transesophageal Doppler, transthoracic impedance, and pulmonary
      artery thermodilution techniques to evaluate the utility of the noninvasive
      methods. Pairs of noninvasive and thermodilution measurements were obtained 25
      times with transesophageal Doppler and 58 times with transthoracic impedance.
      Correlation of the noninvasive measurements with thermodilution was poor, with r
      = 0.43 for transthoracic impedance and r = .68 for transesophageal Doppler. The
      average difference between the noninvasive and the thermodilution values was -0.4
      +/- 1.4 L/min (mean +/- SD) and -0.1 +/- 1.6 L/min for impedance and Doppler,
      respectively. Changes in cardiac output at sequential time points as measured by
      thermodilution were predicted with 95% confidence only when a change of >4 L/min
      was observed by transesophageal Doppler or >8 L/min was observed by transthoracic
      impedance. Therefore, it is concluded that neither noninvasive technique reliably
      estimated cardiac output as determined by thermodilution, and neither tracked
      trends.

PMID- 17171948
TI  - Effect of myocardial revascularization and vein graft blood flow on pacing
      function.
AB  - The effect of myocardial revascularization and vein graft blood flow on pacing
      function was determined in nine patients undergoing aortocoronary bypass. Pacing
      variables including threshold, current, and resistance were measured with a
      pacing system analyzer during intermittent pacing with a transluminal bipolar
      ventricular pacing probe. Pacing function was analyzed immediately before
      cardiopulmonary bypass (CPB) and compared with measurements taken eight minutes
      after full flow through the vein grafts had been established. Comparison of these
      two times showed a significant decrease in resistance, P < 0.003, and threshold,
      P < 0.03. After the second measurement, left anterior descending (n = 8), or
      right coronary (n = 1) vein graft blood flow was interrupted. Pacing variables
      were analyzed at one minute, two minutes, and four minutes following vein graft
      clamping; and a final set of measurements was obtained one minute following
      release of the vein graft clamp. Threshold increased but did not reach
      statistical significance. Resistance increased significantly: P < 0.03. All
      values returned to baseline following release of the vein graft clamp and full
      return of blood flow. The results of this study suggest that pacing function
      measurements are sensitive to changes in vein graft blood flow and may provide
      useful information about the condition of the myocardium, especially immediately
      prior to weaning from CPB.

PMID- 17171949
TI  - Rapid-sequence induction technique in patients with severe ventricular
      dysfunction.
AB  - The hemodynamic effects of a rapid-sequence induction and intubation technique
      using etomidate, fentanyl, and succinylcholine for emergency surgery in patients
      with severe ventricular dysfunction were studied. Ten patients undergoing
      orthotopic heart transplantation received fentanyl, 10 microg/kg, etomidate, 0.3
      mg/kg, and succinylcholine, 1.5 mg/kg, intravenously (IV) in rapid-sequence
      fashion for induction. Intubation was performed 60 seconds later. Heart rate
      (HR), mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary
      arterial pressure (MPAP), pulmonary arterial occlusion pressure (PAo), and
      cardiac index (CI) were measured preinduction, postinduction, and 1 minute after
      intubation. Systemic vascular resistance index (SVRI) and pulmonary vascular
      resistance index (PVRI) were calculated from the measured data. No statistically
      significant changes in hemodynamics occurred with induction or intubation. These
      results indicate that etomidate, fentanyl, and succinylcholine given in a rapid
      sequence technique produce a hemodynamically stable induction with minimal
      response to intubation in patients with end-stage cardiac disease.

PMID- 17171950
TI  - Influence of beta-blockers on vecuronium/sufentanil or pancuronium/sufentanil
      combinations for rapid induction and intubation of cardiac surgical patients.
AB  - Use of pancuronium or vecuronium with the priming principle was evaluated in
      regards to hemodynamic changes and adequacy of relaxation for a rapid induction
      endotracheal intubation sequence with sufentanil in 24 ASA Class III-IV patients
      undergoing cardiac surgery. Twelve patients taking beta-blockers (groups B-P and
      B-V) were compared with 12 patients not receiving beta-blockers (groups NB-P and
      NB-V). Patients randomly received vecuronium or pancuronium (15 microg/kg),
      followed in 4 minutes by sufentanil 5 microg/kg and another 85 microg/kg of the
      appropriate relaxant through a central vein. Intubation was possible in all
      patients at 90 seconds with good-to-excellent conditions. Heart rate (HR)
      remained statistically elevated after induction (90 +/- 10 beats/min) and
      intubation (105 +/- 10 beats/min) only in group NB-P (baseline 74 +/- 12
      beats/min). The NB-P group also had an elevated blood pressure after the priming
      dose. No significant hemodynamic changes were found in the other groups in mean
      arterial pressure, pulmonary artery diastolic pressure, systemic vascular
      resistance (SVRI), or cardiac index (CI). When used with vecuronium, sufentanil
      in a dose of 5 microg/kg provided adequate anesthesia to avoid the hypertensive,
      tachycardic response that frequently occurs following a rapid intravenous (IV)
      induction, without unduly depressing cardiac output or arterial pressure. Two
      patients had evidence of respiratory difficulty after the priming dose,
      associated with transient tachycardia and hypertension which resolved after
      induction. Using the priming principle, either pancuronium or vecuronium rapidly
      provided relaxation in patients with cardiac disease. Chronic beta-blocker
      therapy was able to attenuate the tachycardia from pancuronium and was not
      associated with bradycardia when used with vecuronium. In patients with cardiac
      disease not on beta-blockers, pancuronium was associated with tachycardia.
      Therefore, vecuronium appears to be more suitable for these patients.

PMID- 17171951
TI  - Is sufentanil removed by blood conservation devices?
AB  - To conserve blood during open heart surgery, cell savers and hemoconcentrators
      are used. Cell savers retrieve and filter shed blood from the operative field and
      then wash and separate reconcentrated erythrocytes from a supernatant by
      centrifugation. Hemoconcentrators are extracorporeal devices that extract an
      ultrafiltrate from the circulating perfusate during cardiopulmonary bypass. Both
      cell saver supernatant and hemoconcentrator ultrafiltrate are discarded. Twenty
      patients were anesthetized with a single dose of sufentanil, 30 microg/kg, and
      the cell saver supernatant and hemoconcentrator ultrafiltrate were analyzed for
      sufentanil. The supernatant contained only 0.1% of the total administered dose.
      Hemoconcentrators from two different manufacturers were tested, and 0.1% of the
      administered sufentanil was detected in one ultrafiltrate and none was found in
      the other. Thirty minutes after induction of anesthesia, the plasma sufentanil
      concentration was 8.5 ng/mL (1.3% of the given dose); 1 hour later, it was 4.9
      ng/mL (0.8%). During cardiopulmonary bypass, the plasma level decreased to 2.5
      ng/mL (0.6%); after bypass, it fell to 1.5 ng/mL (0.3%). It is concluded that
      intravenous (IV) sufentanil rapidly leaves the plasma compartment, and little
      remains available to be extracted by the devices used to process and conserve
      blood.

PMID- 17171952
TI  - Fentanyl uptake by the scimed membrane oxygenator.
AB  - With the initiation of cardiopulmonary bypass (CPB), using a membrane oxygenator,
      the drop in circulating fentanyl concentration is greater than can be attributed
      to dilution alone. This study examined the Scimed brand (2A-800) membrane
      oxygenator as a site of fentanyl binding. Initial experiments used an assembled
      CPB circuit. Subsequent dissection and analysis of the oxygenator revealed that
      the silicone-based membrane sheets were the primary site of fentanyl binding. The
      silicone-containing waterproof wrapper was also responsible for 1% to 2% of
      fentanyl binding. Binding of fentanyl to the Scimed membrane oxygenator occurs at
      a rapid rate and continues until the membrane has taken up 130 ng/cm2 of membrane
      surface area. The interaction is complete by 15 to 30 minutes if suprasaturated
      concentrations are used. Samples of membrane material with a surface area of 1
      cm2 were also studied. Isolated membrane squares in a nonmoving prime solution
      required two hours for saturation at the same fentanyl concentrations as the
      intact membrane with circulating prime. Introduction of motion to the priming
      solution accelerated the rate of fentanyl binding by the isolated membrane
      squares to a rate similar to the intact membrane. Motion also provided results
      similar to those previously reported using different analysis techniques.
      Therefore, this method of studying fentanyl-membrane interactions using samples
      of membrane and tritiated fentanyl is a valid model for the intact membrane
      oxygenator in the assembled bypass circuit. In addition to solution movement,
      fentanyl concentration of the priming solution was also found to affect the rate
      of fentanyl uptake. When fentanyl concentrations were used which were
      insufficient to achieve saturation of the membrane (10 ng/mL and 20 ng/mL), the
      rate of uptake was slowed. Binding of all available fentanyl under these
      conditions occurred within three hours. There is potential modification of this
      interaction by several clinically relevant factors, including temperature, pH,
      protein content of prime solution, and other drugs. These areas require further
      study before the saturation data are applied to clinical practice.

PMID- 17171953
TI  - Low-compliance, volume-controlled, high-frequency positive-pressure ventilation
      versus conventional ventilation during coronary artery bypass grafting.
AB  - Low-compliance, volume-controlled, high-frequency positive-pressure ventilation
      (HFPPV) was compared to conventional intermittent positive-pressure ventilation
      (IPPV) immediately before and after surgery in a series of ten patients who
      underwent coronary artery bypass grafting (CABG). Direct and indirect hemodynamic
      and respiratory variables were recorded and calculated. All patients were
      adequately ventilated with either HFPPV or IPPV. No significant differences in
      hemodynamic stability were noted either before or after cardiopulmonary bypass
      (CPB). Airway pressures were lowered significantly by HFPPV as compared to IPPV.
      This may be useful in cases in which increased airway pressure might be harmful
      due to decreased venous return and cardiac output (CO).

PMID- 17171954
TI  - Effects of inspired oxygen tension on hemodynamics and pulmonary gas exchange in
      patients undergoing coronary artery surgery.
AB  - This study was designed to compare the effect of intraoperative administration of
      100% oxygen (F1O2 = 1.0) with 50% O2 (air-O2 mixture, F1O2 = 0.5) on
      cardiovascular and respiratory parameters in adults undergoing coronary artery
      surgery. Nineteen patients were assigned to receive either F,O2 = 1.0 (group A)
      or F1O2 = 0.5 (group B) in a randomized fashion. Anesthesia was induced with
      fentanyl (15 microg/kg) and diazepam (0.1 to 0.2 mg/kg) and maintained with
      fentanyl (total dose 50 microg/kg) and isoflurane. A bubble oxygenator (F1O2 =
      1.0) was used during cardiopulmonary bypass (CPB) in both groups. Hemodynamic and
      respiratory profiles were determined at specific intervals prior to incision,
      following CPB, and postoperatively. Patients ventilated with F1O2 = 0.5 were well
      oxygenated at measured intraoperative intervals (PaO2 range 90 to 268 mmHg,
      saturation 95% to 99%), with adequate mixed venous O2 levels (PvO2 range 35 to 65
      mmHg, saturation 63% to 89%). Compared with patients receiving F1O2 = 1.0, those
      receiving F1O2 = 0.5 had significantly greater increases in cardiac index (CI)
      (mean +/- SEM B: 87% +/- 18% v A: 26% +/- 12%) and stroke index (B: 10% +/- 5%
      increase vA: 14% +/- 7% decrease), and a larger decrease in peripheral resistance
      (B: 38% +/- 7% v A: 4% +/- 12%) at postoperative day 1 relative to preincision
      values (P < 0.05). At postoperative day 1, both groups had an elevated alveolar
      to-arterial O2 gradient (A: 55% +/- 19% v B: 48% +/- 17% increase) and shunt
      fraction (A: 58% +/- 28% v B: 99% +/- 35% increase). Although O2 consumption
      increased similarly in both groups at postoperative day 1 relative to preincision
      values (A: 91% +/- 23% v B: 113% +/- 16%), O2 delivery was enhanced more in group
      B than in group A (67% +/- 17% v 20% +/- 13% increase, respectively, P < 0.05).
      The data suggest that significant hemodynamic derangements may occur with
      hyperoxia and that intraoperative administration of 50% O2 may be more
      appropriate during coronary artery surgery.

PMID- 17171955
TI  - Cardiopulmonary effects of one-lung ventilation in supine patients.
AB  - The cardiopulmonary effects of one-lung ventilation (OLV), with continuous
      positive airway pressure (CPAP, 5 cm H2O) to the nonventilated lung, were
      compared to the effects of two-lung ventilation (TLV) in 12 supine patients
      undergoing coronary artery bypass grafting (CABG). Monitoring was performed with
      electrocardiography (ECG), arterial, and pulmonary artery catheters. Measurements
      of cardiac index (CI), heart rate (HR), systemic (MAP) and pulmonary artery
      pressures (PAP), pulmonary artery occlusion pressure (PAOP), mixed venous oxygen
      saturation (SvO2), and arterial blood for pH, PaO2, PaCO2 and HCO3- were
      performed with stable maintenance of anesthesia during both one- and two-lung
      ventilation. Mean values for CI, HR, MAP, MPAP, PVR, and SvO2 demonstrated no
      significant changes between OLV and TLV; systemic vascular resistance (SVR) and
      pulmonary artery occlusion pressure (PAOP) were statistically (P < 0.05)
      different, but of minor clinical significance. The data suggest that OLV,
      accompanied by CPAP (5 cm H2O) to the nonventilated lung, produces minimal
      changes in cardiopulmonary measurements in supine patients.

PMID- 17171956
TI  - Complement and leukocyte changes during major vascular surgery.
AB  - To gain further insight into the effects of major vascular surgery involving the
      abdominal aorta on complement and leukocytes, serial measurements of leukocyte
      and differential counts, plasma concentrations of C3d, and granulocyte elastase
      bound to alpha1 proteinase inhibitor (E-alpha1PI) were made after aorta
      declamping in a group of patients not receiving blood or plasma. In the hours
      after declamping, lymphocyte count decreased, whereas an increase was noticed in
      leukocytes, neutrophils, and plasma E-alpha1PI. Complement activation was not
      found. Previous reports on complement activation during aortic surgery probably
      reflect the administration of blood and plasma during the surgical procedures.
      Whether aortic cross-clamping or interaction between granulocytes and the aortic
      prothesis is responsible for the release of lysosomal enzymes during the
      procedure warrants further studies.

PMID- 17171957
TI  - Regional myocardial metabolism and electrolyte balance during acute ischemia in
      dogs.
AB  - The relationships among regional (ischemic and nonischemic) myocardial
      extracellular (coronary venous) potassium concentration, potassium-sodium
      concentration ratio, acid-base balance, and metabolism of glucose and lactate
      were evaluated in 14 anesthetized dogs in which ischemia was produced by
      transitory left anterior descending coronary artery (LAD) occlusion. Coronary
      blood samples were obtained from the specific regions by using coronary arterial
      and venous catheters placed directly into the vessel supplying (or draining) that
      region. During ischemia, in coronary venous blood sampled from the ischemic area,
      pH decreased, and PCO2, base deficit, potassium concentration, and the potassium
      sodium ratio increased. In LAD venous blood samples obtained during LAD
      occlusion, the percentage change in potassium concentration was inversely related
      to the percentage change in PCO2 (r = -0.634, P < 0.05), but not to the
      percentage change in hydrogen ion concentration (r = -0.339, P > 0.05). During
      ischemia, arteriovenous O2 content difference in the LAD region increased from
      8.54 +/- 0.73 vol % to 10.71 +/- 0.73 vol %; lactate extraction became negative
      (indicating net production), values decreasing from 27.76 +/- 4.49% to -138.10 +/
      16.81% (P < 0.05); and glucose extraction increased from 14.57 +/- 2.88% to
      19.01 +/- 6.06% (0.05 < P < 0.1). These observations indicate that efflux of
      potassium from the myocardium during ischemia is linked to tissue hypoxia,
      increased glucose extraction, lactate production, and extracellular acidosis. A
      further contributor to potassium release, failure of the normal membrane-bound,
      energy-requiring ion pump, cannot be excluded by these data. With the model used
      in this study, blood can be sampled from discrete regions of the heart, which
      enables the study of interactions between pharmacologic agents, such as
      anesthetics, and the metabolic abnormalities produced by acute ischemia.

PMID- 17171958
TI  - Anesthetic management of patients with carcinoid heart disease undergoing cardiac
      surgery: two case reports and a review of previous experience.

PMID- 17171959
TI  - Thromboelastography used for detection of perioperative fibrinolysis: a report of
      four cases.

PMID- 17171960
TI  - Intravenous labetalol for induced hypotension in an adult patient undergoing
      coarctation repair.

PMID- 17171961
TI  - Postcardiac surgical hypertension.

PMID- 17171962
TI  - Dupont critical care lecture: role of ultrashort-acting beta-blockers in the
      perioperative period.
AB  - beta-blockade can result in extreme bradycardia, significant conduction problems,
      bronchospasm, or left ventricular dysfunction. For this reason, the use of long
      acting beta-blockers is of limited value in the perioperative period. Esmolol,
      due to its ultrashort action and cardioselective properties, has been shown to be
      safe and effective for use in treatment of tachycardia and hypertension. Doses of
      up to 300 microg/kg/min for up to seven hours have been used with a return to
      baseline parameters within 30 minutes of discontinuation of the infusion. It can
      also be safely used in treatment of the asthmatic patient with tachycardia or
      hypertension with no clinically significant increases in airway resistance.
      Studies using esmolol during general anesthesia have also demonstrated that it
      appears to have no significant interaction with various anesthetic agents.

PMID- 17171963
TI  - Case conference. A 77-year-old woman had worsening of her hemodynamics related to
      the use of the intraaortic pump.

PMID- 17171964
TI  - Pro: Blood gases should be corrected for temperature during hypothermic
      cardiopulmonary bypass: pH-stat mode.

PMID- 17171965
TI  - Con: Blood gases should not be corrected for temperature during hypothermic
      cardiopulmonary bypass: alpha-stat mode.

PMID- 17171966
TI  - Society of Cardiovascular Anesthesiologists, New Orleans.

PMID- 17171967
TI  - Double-lumen tube seal against a known pressure gradient.

PMID- 17171968
TI  - Use of right-sided double-lumen tubes.

PMID- 17171969
TI  - Computerized EEG monitoring and carotid endarterectomy.

PMID- 17171970
TI  - Computerized EEG monitoring and carotid endarterectomy.

PMID- 17171971
TI  - Computerized EEG monitoring and carotid endarterectomy.

PMID- 17171972
TI  - [Granulomatous myopathy in patients with sarcoidosis and myasthenia gravis].
AB  - Granulomatous myopathies are extremely rare. The finding of epithelioid
      granulomas in muscle biopsy indicates mostly an involvement of the skeletal
      muscle in systemic sarcoidosis. In this report we provide description of five
      patients with previously diagnosed sarcoidosis (pulmonary or cutaneous), in which
      a clinically significant muscle weakness developed. We aim at demonstrating the
      value of muscle biopsy for further treatment of the patients, since clinically
      indistinguishable myopathies can arise not due to the involvement of muscles in
      the granulomatous process, but due to the corticosteroid-induced changes (chronic
      steroid myopathy). The demonstration of a selective atrophy of type II muscle
      fibers can provide the clue for distinguishing the patients, in which the
      corticosteroid treatment should continue, from those, in which the treatment
      should be modified. Further, we discuss a rare finding of granulomas in muscle
      biopsies of two patients with myasthenia gravis (MG) associated with thymoma.
      Although it is difficult to explain the pathogenesis of this event, MG should be
      considered in the differential diagnosis of granulomatous myopathies. Moreover,
      the finding of granulomas along with lymphocytic infiltration in MG muscle should
      lead to a search for an underlying thymic neoplasm.

PMID- 17171973
TI  - [Lipomatous hypertrophy of the cardiac interatrial septum].
AB  - Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare lesion of
      unknown origin usually diagnosed as an incidental finding during autopsy. It can
      be associated with supraventricular arrhythmias, venous return obstruction and
      sudden cardiac death. Five necropsy cases (4 females, 1 male) of LHIS were
      encountered during the last 31 years; only one case from this series was
      diagnosed ante mortem. The patients' mean age was 68 years; their mean BMI was
      28.4. The mean size of the lesion was 31 mm. In three patients the LHIS was
      asymptomatic, two patients experienced relapsing multifocal atrial tachycardia
      and sick sinus syndrome, respectively. Histologically, all cases consisted of a
      mixture of mature and brown adipose tissue with foci of cardiomyocytes. For a
      pathologist the knowledge of LHIS is important because of an increasing
      possibility of its ante mortem diagnosis by imaging methods with a following
      endomyocardial biopsy, and also because it may appear as a cause of sudden
      cardiac death.

PMID- 17171974
TI  - [Benign mesenchymal stromal tumor of the breast simulating benign schwannoma in
      an 81-year-old male--a case report].
AB  - Presented is an unusual case of a benign mesenchymal stromal tumor of the breast
      in an 81-year-old male. The basic appearance of the lesion simulated benign
      schwannoma and was misinterpreted as a low-grade myxoid liposarcoma initially.
      Well-circumscribed, gray-white mass measuring 35 mm in maximum diameter was
      discovered deep in the parenchyma of the completely removed breast.
      Microscopically, the lesion consisted of myxoid, richly vascular background where
      dominated oval or spindle cells with impressive palisading replicating that of
      benign schwannoma. Rarely, the large multinucleated (floret-like type) cells were
      visible; no nuclear atypia or mitotic figures were found. Immunohistochemical
      examination confirmed expression of estrogen and progesterone receptors, antigen
      Bcl2 and also focal desmin positivity. Clinical examinations disclosed no
      objective reason for possible hyperestrinism; no other therapy followed and the
      patient is free of disease 19 months after operation. On the background of both
      detailed review and differential diagnosis of benign, so-called stromal tumor of
      the female breast, the rarity of this microscopic finding in male is documented.

PMID- 17171975
TI  - [Primitive nonneural granular cell tumor of skin (case report)].
AB  - Primitive nonneural granular cell tumor was recognized in an 82-year-old man,
      mimicking a granuloma in the scalp. Despite its disturbing cytomorphology, this
      histogenetically enigmatic tumor with unusual immunoprophile (NK1-C3, CD 68 and
      NSE positivity; S-100 protein negativity) behaves indolently.

PMID- 17171976
TI  - [Pneumatosis cystoides intestini caeci--a pseudotumor presented at autopsy].
AB  - A large focus of cystic intestinal pneumatosis appeared as an accidental finding
      in a 59-year-old man suffering from obstructive lung disease, with cor pulmonale
      as the cause of death. The gas pseudocysts were found in the submucosa,
      muscularis propria and in the subserosal space. The pseudocysts were lined by
      flattened cells of connective tissue origin with presence of occasional
      macrophages. We believe that the lesion started by focal damage of the mucosal
      membrane, which was followed by penetration of stool particles with microbes into
      the submucosa. E. coli and Morganella morgani are the probable producers of the
      gas bullets.

PMID- 17171977
TI  - [A brief assessment of the scientific programme].

PMID- 17171978
TI  - [Occupational risk and prevention in the biotechnology industry: a review].
AB  - BACKGROUND: The biotechnology industry has expanded greatly in the last 20-30
      years and has led to a number of applications in different sectors of work, i.e.,
      medical and pharmaceutical, agricultural, chemical, energetic and others.
      Nowadays hundreds of thousands of workers worldwide are employed in biotechnology
      plants. Health and safety issues related to such working activities are
      considered as relevant to workers as well as to the general public. In
      particular, when compared to traditional biotechnology, modern methods of
      processing microrganisms have given rise to public concern that they might
      generate hazards to human beings and to the environment. OBJECTIVES AND METHODS:
      After summarizing the most important products and fields of application, the
      paper sets out to detail potential adverse effects for the health of
      biotechnology workers; in addition, an analysis of the literature highlights the
      various concepts of primary and secondary prevention. RESULTS AND CONCLUSION:
      Along with occupational risk factors common to other working activities (i.e. the
      well-known physical and chemical hazards), the peculiarity of handling
      microrganisms and/or different biologic systems may induce infections,
      immunological alterations or non-infective and non-immunologic toxic reactions in
      the workers involved The need is emphasized for an accurate risk assessment,
      careful control by means of the current monitoring strategies and implementation
      of the confinement measures, taking into account the criteria set by Italian
      legislation for occupational biological risk. Lastly, attention is focussed on
      examinations for the medical surveillance of workers at risk.

PMID- 17171979
TI  - [Hymenoptera stings in forestry department agents: evaluation of risk].
AB  - BACKGROUND: In sensitized subjects Hymenoptera stings may provoke the awakening
      of mediated systemic reactions of I type IgE, which can sometimes be serious.
      Considering the type of work performed activity and the high frequency of
      reported hymenoptera sting episodes, a sample of 206 Forestry Department agents
      was surveyed who worked outside urban areas in the Marche Region. OBJECTIVES: The
      aim of the study was to analyse the prevalence of stings and their possible
      systemic reactions, as well as to evaluate the type of occupational risks
      involved. METHODS: A total of 206 agents were examined and questioned about the
      number of stings suffered during work and about the kind of subsequent skin and
      systemic reactions; they were then classified according to the method proposed by
      H.L. Mueller. RESULTS: 179 agents reported having suffered from hymenoptera
      stings and, of these, 53 subjects (29,6%) remembered that one episode at least
      occurred during work. Among 175 operators (98%), 4 had a regular reaction, with
      appearance of a generalized urticaria and uneasiness. In the remaining 4 agents
      (2%) there was a local extensive reaction, which was not associated with systemic
      reactions and they were all referred to allergological examination. 19 agents
      (10,6%) suffered more than 5 stings altogether, but none developed a systemic
      reaction. 87% of the subjects practised self-medication, 7% reported to the
      casualty department of the local hospital or to their own doctor, and 6%
      undertook no cure at all. CONCLUSIONS: Epidemiological studies agree in
      recognizing that, in the general population, the percentage of systemic reactions
      after one or more hymenoptera stings varies from 0,15% to 3,3%. In categories of
      workers occupationally at risk, the prevalence of systemic reactions varies from
      4,5% to 26%. The prevalence of systemic reactions in Forestry Department agents
      was 2%, which is similar to the prevalence in the general population. Therefore,
      rather than occupational risk, there appeared to be a generic risk made more
      serious by working conditions for Forestry Department agents due to their
      possible exposure to hymenoptera stings. The occupational health physician needs
      to monitor these events, due to the fact that frequent exposure to stings, above
      all occurring within a short period of time (less than two months) favours an
      increase in the tendency to develop systemic reactions, with a more serious
      prognosis, especially when working in isolated conditions.

PMID- 17171980
TI  - [Mesothelioma incidence and time trend in the worlds].
AB  - BACKGROUND: Due to its adaptability to different uses, asbestos was increasingly
      employed in many working and domestic areas up to the 1970s-1980s, when its
      aetiological role in the onset of pleural mesothelioma (Mm) was recognized. Since
      then Mm cases have been continuously increasing and no decline is expected until
      2020, despite the fact that most industrialized countries banned asbestos use a
      few decades ago. OBJECTIVES: The aim of this study was to analyse Mm incidence in
      the World during the last ten years, also considering asbestos consumption in
      diferent areas. METHODS: Incidence age-standardized rates (ASR) from Cancer
      Registries included in Cancer Incidence in Five Continents, Vol. VII and VIII,
      and, when appropriate, standardized rate ratio (SRR) with confidence interval
      were estimated. RESULTS: The highest incidence rates among males were observed in
      Liguria and Australia. After Liguria, Maastricht and Scotland in Europe, North
      East Regions and Piedmont in Italy showed high rates. Among females, the highest
      incidence rates were observed in Liguria, among black women in New Orleans and in
      the province of Varese. SRRs revealed increased rates, not always significant, in
      almost all areas among males and in about 50% of the areas among females,
      although the variation was significant only in Varese. CONCLUSIONS: These results
      confirmed a relationship between Mm risk and asbestos use, revealing high
      incidence rates in Australia (mining), Italy (shipyards, building, goods
      handling, heavy industries and sea trade) and Great Britain (shipyards). Mm cases
      increased in areas with elevated incidence rates, suggesting that larger amounts
      of asbestos were probably used for a longer period. Finally, no Mm cases were
      registered in some areas, which probably signifies a lack (or a delay) of risk
      referred to the investigated period.

PMID- 17171981
TI  - Occupational stress: risk assessment and fitness for work.
AB  - The multidimensional and multifaceted aspects of the problem render the role and
      activity of the Occupational Health Physician (OHP) extremely complex and
      delicate, as both appraisal and implications cover a number of different domains
      (psychology, physiology, sociology, economy, work organisation and law), both in
      terms of risk assessment and stress evaluation, at collective and individual
      level. In this context, it is not only important to quantify the "external" work
      load, but mainly the individual "response", which in most cases is the crucial
      factor of the imbalance. that is, risk assessment has to be made more in
      "relative" terms rather than according to "absolute" criteria, and not only from
      the perspective of medical surveillance, but above all from that of risk
      prevention. When a health disability potentially connected to stress has to be
      assessed, there are three steps: a) stress exposure must be clearly assessed,
      both directly and indirectly; b) disease must be clearly identified; c) the
      biological plausibility of the relationship between stress and disease must be
      carefully checked, taking into account that stress disorders are typically
      psychosomatic and multi-causal. Consequently, cooperation with a psychologist and
      an accurate psycho-diagnostic approach are necessary, as well as consultation
      with other specialists and pertinent laboratory and instrumental tests.

PMID- 17171982
TI  - [Gender differences in workplace bullying].
AB  - BACKGROUND: Despite the attention that international Agencies give to the gender
      issue in situations of workplace bullying, few investigations have been performed
      on this topic. OBJECTIVES: The aim of the study is describe the gender
      differences in victims of workplace bullying observed in an Italian survey.
      METHODS: A total of 243 subjects (124 males and 119 females) were examined at the
      Centre for Occupational Stress and Harassment of the "Clinica del Lavoro Luigi
      Devoto" (University of Milan and IRCCS Foundation); they were selected among
      patients who met the criteria for being considered victims of negative actions at
      work leading to workplace bullying. Data regarding the person, workplace and the
      workplace bullying situation were collected by means of an ad hoc questionnaire.
      RESULTS: Analysis of the data, compared with those of IS-TAT 2002, showed a
      higher prevalence of females subjected to negative actions at work. In women, the
      risk of being subjected to negative actions leading to workplace bullying was
      shown to increase in the 34-44 age range and to decrease in higher age ranges; in
      men the risk remained elevated also after 55 years of age. CONCLUSIONS: In
      general, women were victims of negative actions regarding personal values related
      to emotional-relational factors, while men were attacked on their work
      performance. Sexual harassment, may mark the onset of other types of
      psychological harassment or can be one of its components.

PMID- 17171983
TI  - [Application of the OWAS method in the study of work postures among quarry manual
      workers].
AB  - BACKGROUND: Previous ergonomic and epidemiologic studies revealed high postural
      risk (exceeding the N.I.O.S.H. recommended limits) and relevant damage
      (significant excess of acute and chronic lumbosacral spinal disease) among the
      labourers in porphyry quarries in the Province of Trento (Italy). METHODS: An
      analysis of work postures was made with the OWAS (Ovako Working postures
      Analysing System) method. RESULTS: A high prevalence of work postures that have a
      harmful effect on the musculoskeletal system was found. Working methods need to
      be changed as soon as possible. CONCLUSIONS: The use of the OWAS method permits a
      detailed analysis of working conditions in order to identify and re-design the
      activities causing ergonomically problematic postures.

PMID- 17171984
TI  - [Critical aspects of the management of "hazardous" health care workers. Consensus
      document].
AB  - BACKGROUND: A worker is considered to be hazardous to others when, in the course
      of performing a specific work task, his/her health problems (e.g., substance
      dependence, emotional disorders, physical disability, transmissible diseases)
      pose a risk for other workers' or the public's health and safety, or begins to
      interfere with ability to function in profession life. The presence of certain
      illnesses or the fact that a health care worker is impaired because of them do
      not necessarily imply that he, or she, is hazardous for others. Working in health
      care increases the probability that an impaired worker being hazardous for
      others. Management of hazardous workers requires new techniques and procedures,
      and specific policies. OBJECTIVE AND METHODS: An interdisciplinary group of
      experts from medical, bioethical, legal and administrative disciplines, together
      with trade union and employers' representatives, is currently attempting to
      define a way to put prevention measures into practice in accordance with state
      laws and individual rights. RESULTS: A consensus document is presented, covering
      critical aspects such as: social responsibility of the employer, risk management,
      informed consent, non compliance, confidentiality, responsibility of workers,
      disclosure of risk to patients, non-discrimination, counselling and recovery of
      impaired workers, effectiveness of international guidelines. CONCLUSIONS:
      Occupational health professionals are obliged to adhere to ethical principles in
      the management of "hazardous" workers; the assessment of ethical costs and
      benefits for the stakeholders is the basis for appropriate decisions.

PMID- 17171986
TI  - [Congress "The occupational physician and new obligations concerning noise and
      vibrations" -- Milan, 20 April 2006].

PMID- 17171985
TI  - [Information of the registry of mesothelioma in Lombardy: the asbestos risk in
      rotogravure].

PMID- 17171987
TI  - [Role of interventional catheterization in adults with congenital heart disease].
AB  - The advances in surgical and interventional treatment of congenital heart
      diseases have allowed a large number of patients with congenital heart disease to
      attain the adult age. This population involves almost 0.3/1000 of the total
      population in Western Europe and North America and can be estimated to be 25,000
      patients in Italy. Patients with operated tetralogy of Fallot, benign forms of
      pulmonary atresia with ventricular septal defect, simple or complex transposition
      of the great arteries usually survive beyond childhood. These patients may need
      repeat interventions to treat lesions of native or reconstructed pulmonary
      arteries and/or aortic arch, to occlude residual shunts, to treat pulmonary
      incompetence. More complex heart diseases such as single ventricle, rarely allow
      survival until the adult age. The majority of these patients undergo heart
      transplant, often made difficult by multiple cardiac surgical interventions,
      anomalies of the pulmonary arteries, chronic cyanosis, and aorto-pulmonary
      shunts. Patients with relatively simple or complex congenital heart diseases need
      to be followed in specialized units, like those existing in the United States,
      Canada, and Great Britain.

PMID- 17171988
TI  - [Pseudoischemic ST-segment due to atrial repolarization during exercise test.
      Review of the literature, diagnostic criteria and personal experience].
AB  - Atrial repolarization wave has been known since many years: it is opposite in
      direction to P wave, may have a magnitude of 100 to 200 microV and may extent
      into the ST segment (usually it is hidden in the QRS complex). It was
      hypothesized that this wave could cause ST-segment depression mimicking
      myocardial ischemia. The false positive response is characterized by marked
      downsloping of the PR segment at peak exercise, longer exercise time (> 6 min),
      peak exercise heart rate > 125 bpm, absence of chest pain and ST-segment
      normalization in the first minute of recovery. In our experience a role of atrial
      repolarization in ST-segment depression was found in 5.5% of 144 consecutive and
      non-selected individuals evaluated with exercise testing.

PMID- 17171989
TI  - [Heparin-induced thrombocytopenia: implictions for cardiologist].
AB  - Heparin-induced thrombocytopenia (HIT) is one of the most life-threatening
      adverse effects of heparin administration. It is characterized by
      thrombocytopenia and may also be associated with venous or arterial thrombosis.
      HIT type 2 is caused by the binding of antibodies, most likely IgG, to a complex
      of heparin and platelet factor-4, these complexes IgG/PF4/heparin activate
      platelets causing the release of pro-thrombotic particles that promote thrombin
      generation. HIT and HIT-thrombosis are associated with high morbidity and
      mortality. Thrombotic events are most frequently venous and may manifest as
      pulmonary embolism or cerebral venous thrombosis. Arterial thrombosis leading to
      limb damage and amputation and to myocardial infarction or stroke may also occur.
      HIT is a clinical syndrome that requires clinical and laboratory findings to
      confirm the diagnosis. All forms of heparin treatment should be stopped once HIT
      is suspected and patients should be treated with an alternative anticoagulant to
      treat and prevent thrombotic complications. Available alternative anticoagulants
      include argatroban and lepirudin, a recombinant form of hirudin.

PMID- 17171990
TI  - [What does "p" mean at conclusion of a test of hypothesis in a randomized
      controlled clinical trial of superiority?].
AB  - The aim of this statistical note, the sixth in the series, is to introduce the
      rationale of the test of hypothesis suitable for comparing the effect of two
      treatments in a randomized controlled clinical trial of superiority. The
      presentation takes advantage of the analogy with a criminal trial debate based
      upon circumstantial evidence in an Italian Court. The results of three randomized
      controlled clinical trials: ISIS-1, AIMS and RESTORE are introduced and proper
      ways for their interpretation are suggested.

PMID- 17171991
TI  - [A new entry: updates on IN-CHF].

PMID- 17171992
TI  - [Italian Network on Congestive Heart Failure: ten-year experience].
AB  - IN-CHF is a multicenter registry, designed in 1995 to compile a large clinical
      database on the epidemiological, clinical characteristics, management and
      outcomes of heart failure outpatients. Main objectives of IN-CHF registry were to
      provide cardiological centers with a software to collect data of outpatients
      during office visit, for educational purpose; and to enter local data into a
      national registry (IN-CHF registry), for scientific purpose. Entry into the
      database required a diagnosis of heart failure according to the guidelines of the
      European Society of Cardiology. The central coordinator of the project was the
      ANMCO Research Center. The Italian cardiological centers participating in the
      project are 142, they are well representing the entire country and from March
      1995 to July 2005 collected data from 23 855 outpatients. The mean age of the
      patients was 65+/-13 years and 71.3% were men. Main etiologies were ischemic in
      39.4%, hypertensive in 15.8 %, and due to dilated cardiomyopathy in 29%. More
      than half of the patients (55.3%) had a history of admission for heart failure
      within the last year; 25.8% of the patients were in NYHA class III-IV, 9.5%
      showed a heart rate > 100 bpm and 16.5% third heart sound. Left ventricular
      ejection fraction was severely depressed (< 30%) in 27.6% of the patients, while
      it was > 40% in 30.9%. Renal dysfunction was present in 3.6% of the patients
      (serum creatinine level > 2.5 mg/dl), pulmonary disease in 18.7%, diabetes in
      16.8% and anemia (hemoglobin < 12 g/dl) in 18.7%. A history of arterial
      hypertension was common (30.3%); 20.0% and 18.5% of the patients showed atrial
      fibrillation and left bundle branch block, respectively. Data from our registry
      provide important insights into clinical and epidemiological characteristics of
      heart failure outpatients followed in Italian cardiological centers. Starting
      from this article, every 3 months, the most relevant epidemiological data
      collected by the IN-CHF investigators will be published.

PMID- 17171993
TI  - [Electrical storms in patients with implantable cardioverter-defibrillator:
      incidence and clinical management].
AB  - BACKGROUND: Electrical storm in implantable cardioverter-defibrillator (ICD)
      recipients is a dramatic experience for the patient and a hard emergency for the
      cardiology team. The aim of our study was to evaluate the incidence and the
      clinical significance of electrical storm in a standard population of ICD
      patients. METHODS: We considered retrospectively 262 consecutive ICD patients
      (86% males, mean age 65+/-10.7 years). Patients were divided into three groups:
      88 patients without appropriate ICD therapy (group A); 140 patients with isolated
      ICD therapies (group B); 34 patients with electrical storm episodes (> or = 3
      appropriate ICD therapies/24 h) (group C). Survival study (endpoint death) was
      performed for each group of patients. RESULTS: There was no difference in age,
      sex, heart disease, ejection fraction or NYHA functional class among the three
      groups. ICD implant was performed for secondary prevention in 79% of group C
      patients and in 74.3 % of group B patients, but only in 39.8 % of group A
      patients (p < 0.0001). Mean follow-up was 31.1+/-29.8 months in group A, 55.1+/
      38 months in group B, and 71.1+/-51.7 months in group C. The endpoint was reached
      by 16 patients (18%) of group A, by 53 patients (38%) of group B, and by 20
      patients (58%) of group C. Comparison of the survival curves of the three groups
      did not show significant differences. In group C patients, 54 electrical storm
      episodes were recorded (mean 1.5/patient). CONCLUSIONS: In our population of ICD
      patients, we observed electrical storm in 34 patients (12.9%). Survival in group
      with episodes of electrical storm was comparable to patients without electrical
      storm; thus, in our experience, electrical storm could not represent a negative
      prognostic factor.

PMID- 17171994
TI  - [Electrocardiographic pattern of Brugada syndrome during fever and podagra].
AB  - We report the case of a 42-year-old man from Madagascar who, having fever and
      pain in his left big toe, underwent electrocardiography, which showed the pattern
      of Brugada syndrome. These peculiar electrocardiographic abnormalities in Brugada
      syndrome warrant caution for physicians working in the emergency room because
      they may be mistaken as signs of acute myocardial infarction or acute
      pericarditis. In this case report the typical electrocardiographic abnormalities,
      their variability, the effects of fever, and the role of electrode position are
      discussed.

PMID- 17171995
TI  - [Incidental finding of congenital fistula beween the right coronary artery and
      the coronary sinus: integrated echocardiography, multislice computerized
      tomography, and heart catheterization].

PMID- 17171996
TI  - [Beating heart coronary surgery: significance of systematic use].

PMID- 17171997
TI  - Reflections on Global Forum on Leprosy Control.

PMID- 17171998
TI  - Health systems research training as a tool for more effective Hansen's disease
      control programmes in Brazil.
AB  - In Brazil, Hansen's disease (HD) is still a public health problem. Although much
      progress has been made in Hansen's disease control (HDC) at all levels of
      government over the past 20 years, efforts have been hampered by information gaps
      related to specific areas of the disease, exacerbated by an absence of
      appropriate evaluation instruments and routine systematic analysis. Health
      Systems Research (HSR) aims to collect the necessary data to provide the most
      relevant information to policy makers and health managers to take more informed
      decisions. In Brazil, four HSR courses on HDC were organized by two non
      governmental organizations (NGOs), Netherlands Leprosy Relief (NLR) and the
      British Leprosy Relief Association (LEPRA) between 2001 and 2005. Key personnel
      working in HDC from various states were invited to participate in the courses.
      The research proposals were developed during an HSR workshop and carried out in
      the field. The research topics of the projects included the following: the
      integration of HDC programmes into the primary health care system; the high
      percentage of the new patients diagnosed and treated at state referral centres;
      the psychological and social impact of surgical rehabilitation; the efficacy of
      neurolysis; the quality of the national health information system and the
      effectiveness of new case detection and health education campaigns. Following the
      completion of the field work, the data were analysed and a research report
      written. The results and recommendations were later presented to key stakeholders
      and policy makers in the states. Practical outcomes of the HSR courses include
      the drafting of new HDC guidelines; improvement of health information system
      databases and the revision of epidemiological data. These results have been
      presented at national and international congresses and published in peer-reviewed
      jornals. HSR has had a positive impact on the working routines of trainees
      through the process of learning the research methodology, collecting relevant
      data and implementing the recommendatons that originate from the findings. We
      conclude that HSR is an important vehicle for human resource development and a
      practical tool to improve the effectiveness of HDC programmes, primarily at the
      state and municipal levels. HSR also is an example of a successful cooperation
      between NGOs and governmental organizations working in HDC.

PMID- 17171999
TI  - Genetics of host response in leprosy.
AB  - In this review, we discuss recently accumulated data, analysing genetic influence
      on leprosy outcome. Most leprosy-related epidemiological studies are based on the
      comparison of frequencies of genetic markers in case-control designs using
      candidate genes, mainly on immunological pathways. Genomic scans using family
      based designs also identified some chromosome regions to be tested for
      association with leprosy. The results have suggested that different genes are
      implicated in resistance/susceptibility to leprosy, such as tumour necrosis
      factor-alpha (TNFalpha), interleukin (IL)-10, vitamin D receptor (VDR), and
      parkin, although some of the results obtained in different populations are
      controversial. In spite of the recent advances in genomics and genetic
      epidemiology we have experienced, the results must be confirmed using better
      designed epidemiological studies to directly pinpoint the genes responsible for
      leprosy outcome. Furthermore, there is a clear requirement of
      functional/biological data in order to validate epidemiological findings. In this
      way, these genetic markers could be used to screen high-risk populations
      introducing gene testing as diagnostic and prognostic tools to interrupt the
      chain of transmission and prevent neurological damage.

PMID- 17172000
TI  - Prevalence and characteristics of depression in a Japanese leprosarium from the
      viewpoints of social stigmas and ageing. A preliminary report.
AB  - OBJECTIVE: To investigate the prevalence and characteristics of depressed
      patients living in a Japanese leprosarium who have been isolated by national law
      and are now becoming very elderly. METHODS: We surveyed the prevalence of
      depressed patients living in the National Tamazenshouen Sanatorium, a major
      leprosarium in Japan. We also investigated the characteristics of patients who
      had suffered a depressive episode during the last 5 years (2000-2004). The
      characteristics of residents who committed suicide were also studied. RESULTS: At
      the time of the investigation, 48 out of 385 (12.5%) patients were depressed or
      had experienced a depressive episode. Forty-one residents had committed suicide
      since the leprosarium was established in 1907. Somatic symptoms and depressive
      moods were the predominant symptoms and were not limited to symptoms unique to
      leprosy. The period of isolation was not statistically correlated with the GDS-SF
      or PGC morale scale scores. CONCLUSION: The findings of this study emphasize the
      importance of consultation psychiatric for elderly leprosy residents and could be
      used as a reference for treatment in countries with ageing leprosy residents.

PMID- 17172001
TI  - Leprosy control activities in India: integration into general health system.
AB  - Integration of leprosy control into the general health system is an essential
      element of a leprosy elimination strategy. In India, the process has been
      undertaken with the assistance of World Bank in a phased manner. In the first
      phase (2001-2002), 24 low/moderately endemic provinces for leprosy were targeted.
      Operational research was undertaken in these low/moderate endemic provinces to
      assess the progress of integration of leprosy control in general health system
      using defined categories, viz. structural integration, training status,
      availability of MDT and recording/reporting of cases. Selection of nine
      provinces, 18 districts, 86 health facilities and 108 sub-centres was performed
      using multistage stratified random sampling technique. Data were collected by
      interviewing GHS/vertical staff, scrutiny of records and spot checking of MDT
      stock by Health officers of three leprosy institutions of the Government of
      India. The result showed that district leprosy nuclei had formed in 16 of 18
      districts. In 56% of health facilities vertical staff were redeployed for
      delivering general health care. Forty-five percent of medical officers, 71% of
      health supervisors and 75% of multipurpose workers were trained in leprosy. MDT
      treatment was available in >80% of health facilities. In only 2% of health
      facilities 3 months MDT stock of all types was present. Forty-four percent of sub
      centres were delivering subsequent doses (second dose onward) of MDT. Reporting
      through a simplified information system was universal. This study emphasizes the
      need for reorientation training of Medical Officers, better MDT stock management
      and decentralized management of cases up to sub-centre level.

PMID- 17172002
TI  - Relapse in MB leprosy patients treated with 24 months of MDT in south west China:
      a short report.
AB  - This study investigates the relapse rate among multibacillary leprosy patients
      treated with 24 months of MDT in south west China. A retrospective relapse survey
      was conducted in the southwest of China. A detailed questionnaire was designed to
      collect the data on relapse among MB patients who completed 2 years of the WHO/MB
      regimen, from 1989 to 2000. The data about 2517 multibacillary leprosy patients
      in 27 counties in the southwest of China were collected. Among 2517 MB patients,
      235 patients died or were lost to follow-up and 2374 were followed up for more
      than 3 years after completion of MDT. The total duration of follow-up was 20,825
      person-years, with a mean duration of 8.27 years per patient. Five patients with
      relapse were identified with an accumulated relapse rate of 0.21/1000 person
      years. Their initial BIs ranged from 1.8 to 5. The patients with relapse occurred
      48-158 months after the completion of MDT. The relapse rate of MB patients
      treated with 24 months of the WHO/MB regimen was observed to be very low after
      long-term follow-up.

PMID- 17172003
TI  - Role of azathioprine in preventing recurrences in a patient of recurrent erythema
      nodosum leprosum.
AB  - The pathogenesis of erythema nodosum leprosum (ENL) involves both immune complex
      deposition and dysfunction of cell mediated immunity. Tumour necrosis factor
      alpha (TNF-alpha) plays an important role in its pathogenesis. Thalidomide and
      corticosteroids are the mainstay of treatment for ENL. However, there are often
      severe limitations to their use. We report a case of recurrent ENL treated
      successfully with azathioprine. A 15-year-old unmarried girl with lepromatous
      leprosy had recurrent ENL for 2 years. She was treated with WHO-MB MDT and
      prednisolone in doses of 40-90 mg a day for 2-12 weeks. Her condition was
      inadequately controlled. The patient was therefore treated with thalidomide 300
      mg and prednisolone 40 mg. The symptoms subsided after 5 days and ENL lesions
      healed in 2 weeks. Prednisolone was reduced by 10 mg per week and stopped, while
      thalidomide was reduced to 100 twice daily after 4 weeks. Azathioprine 100 mg (2
      mg/kg per day) daily orally was added to prevent recurrences. Thalidomide was
      further reduced and stopped after another 4 weeks while she continued with
      azathioprine in the same doses for 8 months. There was no recurrence of ENL
      lesions and no side effects of the therapy. MB-MDT was stopped 1 year ago, and
      she is on follow-up without any relapse. Azathioprine, therefore, appears to be
      an effective and safe drug to prevent recurrences of ENL.

PMID- 17172004
TI  - Global strategy for further reducing the leprosy burden and sustaining leprosy
      control activities 2006-2010. Operational guidelines.
AB  - The Global Strategy for further reducing the leprosy burden and sustaining
      leprosy control activities (2006 - 2010) has been widely welcomed and endorsed.
      The overall goal is to provide access to quality leprosy services for all
      affected communities following the principles of equity and social justice. The
      purpose of these Operational Guidelines is to help managers of national health
      services to implement the new Global Strategy in their own countries. This will
      be done as they develop detailed policies applicable to their own situation, and
      revise their National Manual for Leprosy Control. Leprosy services are being
      integrated into the general health services throughout the world; a new emphasis
      is given here to the need for an effective referral system, as part of an
      integrated programme. Good communication between all involved in the management
      of a person with leprosy or leprosy- related complications is essential. These
      Guidelines should help managers to choose which activities can be carried out at
      the primary health care level and for which aspects of care patients will have to
      be referred. This will depend on the nature of the complication and the capacity
      of the health workers to provide appropriate care at different levels of the
      health system. The promotion of self-reporting is now crucial to case detection,
      as case- finding campaigns become less and less cost-effective. It is important
      to identify and remove barriers that may prevent new cases from coming forward.
      The procedures for establishing the diagnosis of leprosy remain firmly linked to
      the cardinal signs of the disease, but the accuracy of diagnosis must be
      monitored. The Guidelines suggest a greater emphasis on the assessment of
      disability at diagnosis, so that those at particular risk can be recognized and
      managed appropriately. The treatment of leprosy with MDT has been a continuing
      success; neither relapse nor drug-resistance are significant problems and the
      regimens are well- tolerated. Clear procedures are given for managing irregular
      treatment with MDT. Leprosy reactions are a serious complication affecting some
      patients. The Guidelines contains this aspect, with additional references under
      Further Reading. A key decision for programme managers is to determine how and at
      which level of the health system leprosy reactions are to be managed in their
      country. Different countries must develop their own detailed guidelines on this
      issue. Prevention of disability (POD) is also described in some detail as there
      is a need for much greater coverage with basic POD activities. This is an
      important component of 'quality leprosy services' emphasized in the Global
      Strategy. Items mentioned under Further Reading will be essential for programmes
      planning to build capacity and increase their service provision in this area.
      Rehabilitation may include a medical component (such as reconstructive surgery)
      but its scope is much broader. It is likely that some people affected by leprosy
      would benefit from socio-economic rehabilitation (for example, vocational
      training or a small loan). Staff in the health services need to be familiar with
      what is being done in the locality, and know how and where to refer people who
      need these services. Recording and reporting are essential to maintain quality in
      any programme. The indicators selected in the Global Strategy are useful for
      monitoring and evaluation, and they determine which data must be recorded. The
      data needed to monitor POD activities have not been collected routinely in the
      past, so this represents a significant change - national managers must therefore
      decide for themselves which indicators will be used to ensure quality as these
      will vary from country to country. Programme management is a broad subject; the
      topics covered in this Section are those that are central to the running of
      integrated leprosy control services, including supervision, supply of MDT,
      partnerships, training and programme evaluation.

PMID- 17172005
TI  - Dietary magnesium deficiency decreases plasma melatonin in rats.
AB  - It has been postulated that Mg depletion is associated with decreased melatonin.
      Exogenous magnesium (Mg) has been found to increase the activity of serotonin N
      acetyltransferase, an enzyme in the pathway for melatonin synthesis; but no data
      have been found on the effect of Mg deficiency on plasma melatonin. This pilot
      study examined the effect of a dietary Mg deficiency on plasma melatonin in male,
      Sprague-Dawley rats. Weanling rats were placed on a Mg-deficient (150 ppm) or a
      Mg-adequate (1000 ppm) diets for four weeks, after which they were sacrificed 4,
      5 or 7 hours into the dark cycle. Plasma was assayed for melatonin
      concentrations. A significant decrease (p = 0.0101) occurred in mean (+/- SEM)
      plasma melatonin levels of the Mg-deficient animals (50 +/- 6.4 pg/mL) when
      compared to the Mg-adequate animals (75 +/- 6.6 pg/mL). There was no obvious
      phase shift in the melatonin profile of the Mg-deficient animals when compared to
      the Mg-adequate animals.

PMID- 17172006
TI  - Serum magnesium profile in heroin addicts: according to psychiatric comorbidity.
AB  - Psychiatric comorbidity in heroin addiction can modify both the biological
      pattern and clinical course of this disorder. Because of the role of magnesium in
      neurotransmission and its specific patterns in some psychiatric conditions, such
      as depression and schizophrenia, we studied a sample of heroin dependent
      subjects, with and without psychiatric comorbidity. A sample of 162 drug addicts
      (123 men and 39 women, mean age 32.3 +/- 6.7) was diagnosed for the presence of
      psychiatric comorbidity with DSM IV criteria. They were subsequently divided in 4
      subgroups: No comorbidity, Anxiety Disorders, Mood Disorders, Personality
      Disorders. Differences in serum magnesium level between the groups were analysed
      with the Anova method, with age as covariate. Results show that serum Mg++ levels
      are significantly higher in patients with heroin dependence and personality
      disorders compared to patients with depression comorbidity and without
      comorbidity. Psychiatric codiagnosis significantly modifies Mg++ levels in this
      drug dependent sample. Gender modifies Mg levels in no comorbid subjects so that
      females show significantly lower Mg++ levels compared to males. The presence of
      psychiatric comorbidity abates this difference.

PMID- 17172007
TI  - Contents of bioelements and toxic metals in a Polish population determined by
      hair analysis. Part 2. Young persons aged 10-20 years.
AB  - The aim of this study was to define referential values of 5 basic bioelements
      (Ca, Mg, Zn, Cu, Fe) in the hair of Polish young persons aged 10-20 years, based
      on the research conducted from 1991 to 2004 on a group of over 3420 healthy young
      persons. Mean concentrations of two toxic metals (Pb and Cd) in over 2000 young
      men were also investigated. The results of biochemical tests were analyzed with
      the program STATISTICA 7.0 (StatSoft PL). Significant differences between girls'
      and boys' hair Ca, Mg and Zn in the same age group were observed (p = 0.0000). It
      was determined that boys have smaller concentrations of hair Ca, Mg and Zn than
      girls. No significant differences were observed between concentrations of Cu and
      Fe in the hair of girls and boys of the same age in the tested period.
      Significantly greater amounts of Pb and Cd characterize boys. Analyses of
      correlations confirm significance (p < 0.05000) of synergistic interactions
      between bioelements: Ca-Mg (r = +0.80), Ca-Zn (r = +0.52), Ca-Cu (r = +0.14), Mg
      Zn (r = +0.50), Mg-Cu (r = +0.13), Zn-Cu (r = +0.11), Cu-Fe (r = +0.04).
      Significance (p < 0.05000) of antagonistic interactions of bioelements with toxic
      metals: Zn-Pb (r = -0.30), Mg-Pb (r = -0.20), Ca-Pb (r = -0.18) and Zn-Cd (r = 
      0.07) was confirmed. Significance (p < 0.05000) of synergistic effects with toxic
      elements: Pb-Cd (r = +0.34), Fe-Pb (r = +0.22), Fe-Cd (r = +0.13) was determined.
      Compatibility of the statistically mapped basic characteristics of young persons'
      developmental age with the functions of concentrations in tested hair bioelements
      was confirmed. Young persons whose concentrations of selected hair bioelements
      showed values outside the reference ranges and who had higher concentrations of
      toxic metals should undergo further diagnostic tests since the results of
      previous tests could be a sign of disturbances leading to various diseases.
      Analyses of the concentrations of bioelements and toxic metals in humans based on
      hair analysis can be useful as a convenient, non-invasive and painless method in
      the diagnosis of pathological states. Combined with other analytical data, this
      method can be used by practising physicians as a complementary diagnostic
      procedure.

PMID- 17172008
TI  - Update on the relationship between magnesium and exercise.
AB  - Magnesium is involved in numerous processes that affect muscle function including
      oxygen uptake, energy production and electrolyte balance. Thus, the relationship
      between magnesium status and exercise has received significant research
      attention. This research has shown that exercise induces a redistribution of
      magnesium in the body to accommodate metabolic needs. There is evidence that
      marginal magnesium deficiency impairs exercise performance and amplifies the
      negative consequences of strenuous exercise (e.g., oxidative stress). Strenuous
      exercise apparently increases urinary and sweat losses that may increase
      magnesium requirements by 10-20%. Based on dietary surveys and recent human
      experiments, a magnesium intake less than 260 mg/day for male and 220 mg/day for
      female athletes may result in a magnesium-deficient status. Recent surveys also
      indicate that a significant number of individuals routinely have magnesium
      intakes that may result in a deficient status. Athletes participating in sports
      requiring weight control (e.g., wrestling, gymnastics) are apparently especially
      vulnerable to an inadequate magnesium status. Magnesium supplementation or
      increased dietary intake of magnesium will have beneficial effects on exercise
      performance in magnesium-deficient individuals. Magnesium supplementation of
      physically active individuals with adequate magnesium status has not been shown
      to enhance physical performance. An activity-linked RNI or RDA based on long-term
      balance data from well-controlled human experiments should be determined so that
      physically active individuals can ascertain whether they have a magnesium intake
      that may affect their performance or enhance their risk to adverse health
      consequences (e.g., immunosuppression, oxidative damage, arrhythmias).

PMID- 17172009
TI  - Mechanisms, regulation and pathologic significance of Mg2+ efflux from
      erythrocytes.
AB  - Mg2+ efflux from erythrocytes can be performed by the Na+/Mg2+ antiport and by
      Na+-independent Mg2+ efflux. Na+-independent Mg2+ efflux functions via the
      unspecific choline exchanger as choline/Mg2+ or K+/Mg2+ antiport and as Mg2+
      efflux accompanied by intracellular Cl- for charge compensation, as found for
      example in sucrose medium. Na+/Mg2+ antiport in erythrocytes exchanges 2
      extracellular Na+ for 1 intracellular Mg2+. Driving forces are the Na+ and Mg2+
      gradients. By reversing these gradients, the Na+/Mg2+ antiporter can mediate Mg2+
      influx. The Na+/Mg2+ antiporter can exchange 24Mg2+ for 28Mg2+ and other divalent
      cations for intracellular Mg2+. In the exchange mechanism, extra- and
      intracellular Na+ can compete with Mg2+. Na+/Mg2+ antiport is inhibited by
      amiloride, quinidine and imipramine. Na+/Mg2+ antiport is drastically activated
      by intracellular Mg2+ due to an allosteric transition. The affinity of
      intracellular Mg2+ to the Na+/Mg2+ antiporter is dependent on intracellular ATP
      due to phosphorylation. Besides this mechanism, in non Mg2+-loaded erythrocytes,
      the activity of Na+/Mg2+ antiport is regulated by phosphorylation
      dephosphorylation and by intracellular Cl-. The drastically Mg2+-activated
      Na+/Mg2+ antiporter is not further stimulated by phosphorylation and
      intracellular Cl-. Na+-independent Mg2+ efflux via the choline exchanger is also
      inhibited by amiloride, quinidine and imipramine, and can also be regulated by
      phosphorylation-dephosphorylation. Na+/Mg2+ antiport of erythrocytes is altered
      in various pathologic conditions.

PMID- 17172010
TI  - Ageing, hippocampal synaptic activity and magnesium.
AB  - Ageing is associated with a general decline in physiological functions. Amongst
      the different aspects of body deterioration, cognitive impairments, and
      particularly defects in learning and memory, represent one of the most frequent
      features in the elderly. However, a great variability exists among aged subjects.
      Clinical reports and experimental data in animal models of ageing have shown that
      age-associated memory deficits are broadly identical to those induced by damage
      to the hippocampus. It is therefore not surprising that many functional
      properties of hippocampal neuronal networks are particularly altered with ageing.
      Whereas passive membrane properties of neurons are conserved with age, neuronal
      excitability is altered, in keeping with weaker performances of aged subjects in
      memory tasks. Synaptic transmission within hippocampal networks also decreases in
      brain ageing. Deficits concern both glutamatergic and cholinergic pathways, which
      represent the main excitatory neurotransmitter systems responsible for neuronal
      communication in the hippocampus. In addition, long-term changes in synaptic
      transmission, possible cellular substrates for learning and memory, are also
      impaired in ageing in correlation with cognitive impairments. Neuronal properties
      and synaptic plasticity closely depend on ion exchanges between intra- and
      extracellular compartments. Changes in ion regulation during ageing may therefore
      participate in altering functional properties of neuronal networks. Calcium
      dysregulation has been extensively investigated in brain ageing but the role of
      magnesium has received less attention though ageing constitutes a risk factor for
      magnesium deficit. One of general properties of magnesium at presynaptic fibre
      terminals is to reduce transmitter release. At the postsynaptic level, it closely
      controls the activation of the N-methyl-D-aspartate receptor, a subtype of
      glutamate receptor, which is critical for the expression of long-term changes in
      synaptic transmission. In addition, magnesium is a cofactor of many enzymes
      localized either in neurons or in glial cells that control neuronal properties
      and synaptic plasticity such as protein-kinase C, calcium/calmodulin-dependent
      protein kinase II and serine racemase. It is therefore likely that a change in
      magnesium concentration would significantly impair synaptic functions in the aged
      hippocampus. Experiments addressing this question remain too scarce but recent
      data indicate that magnesium is involved in age-related deficits in transmitter
      release, neuronal excitability and in some forms of synaptic plasticity such as
      long-term depression of synaptic transmission. Further studies are still
      necessary to better delineate to what extent magnesium contributes to the
      impaired cellular mechanisms of cognitive functions in the elderly which will
      help to develop new strategies to minimize age-related memory declines.

PMID- 17172011
TI  - [Isolation, identification and over- siderophores production of Pseudomonas
      fluorescens sp-f].
AB  - Strain sp-f was isolated, a siderophores over producing bacterium, using an
      improved universal Chrome Azurol S(CAS)-agar plate method from Donghu Lake. The
      result of the CAS solution siderophores quantitative determination showed the
      lowest As/Ar (OD680) ratio could be as low as 0.09 with Su (Siderophore Unit) of
      90%. Some more experiments were made to make out the pertinence between its
      growth and siderophores production, indicating that its siderophores quantity
      reached maximum amount during the prophase of logarithmic growth. After then,
      siderophores concentration stopped accumulating and turned to be stable at
      stationary phase. Based on the characteristics of morphology, cultivation,
      physiology, (G + C) mol % content, 16S rDNA sequence and BIOLOG Station system
      analysis, it was identified as Pseudomonas fluorescens sp-f strain. RP-HPLC
      analysis showed there exist at least 3 kinds of catecholate siderophores,
      including fluorescent and non-fluorescent pyoverdins. But only fluorescent
      pyoverdin's excretion was completely repressed by the 200 micromol/L Fe2+ in the
      medium. And the non-pyoverdin siderophores excretion was induced at the same
      time, contrarily.

PMID- 17172012
TI  - [Isolation and phylogenetic analysis of one actinomycete strain YIM 90022
      exhibiting anticancer activity].
AB  - One facultative alkaliphilic actinomycete strain YIM 90022 was isolated from
      hypersaline alkaline soil in Qinghai province, China. An almost-complete 16S rRNA
      gene sequence (1500 bp) for strain YIM 90022 was obtained. Phylogenetic analysis
      based on 16S rRNA gene sequences showed that strain YIM 90022 was closely related
      to four members of the genus Nocardiopsis with 16S rRNA gene sequence similarity
      values of 98.8% (N. exhalans DSM 44407T), 98.5% (N. prasina DSM 43845T), 98.4%
      (N. metallicus DSM 44598T) and 97.8% (N. listeri DSM 40297T), but represented a
      distinct phylogenetic lineage. Repetitive element sequence-based PCR (rep-PCR)
      genomic fingerprinting was evaluated on strain YIM 90022 and its closest
      relatives to investigate their genetic relatedness. The analysis of the rep-PCR
      genomic fingerprints showed that strain YIM 90022 was distinguishable from its
      closest relatives. The polyphasic taxonomic data presented in this study,
      including its morphology, physiological and biochemical characteristics,
      chemotaxonomy, 16S rRNA gene sequence-based phylogenetic analysis and rep-PCR
      genomic fingerprinting, supported the view that strain YIM 90022 represented a
      potential new species of the genus Nocardiopsis. The fermentation broth of strain
      YIM 90022 strongly inhibited growth of cell series of gastric cancer, lung
      cancer, mammary cancer, melanoma cancer, renal cancer and uterus cancer. Strain
      YIM 90022 grew well on most tested media, producing exuberant vegetative hyphae
      and aerial hyphae. The vegetative hyphae are long and fragmented. Light yellow to
      deep brown diffusible pigments were produced on ISP 2, ISP 3 and ISP 6. Growth of
      the strain occurred in the pH range 6.0-12.0, with optimal pH8.5. The NaCl
      tolerate range was 0-15% (W/V). Cell walls contain meso-diaminopimelic acid and
      have no diagnostic sugars. Polar lipids are phosphatidylcholine,
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmethylethanolamine.
      Major menaquinones are MK-10 (H4, H6). The DNA G + C content is 71.5 mol %.

PMID- 17172013
TI  - [Molecular characterization of O-antigen gene cluster of Escherichia coli O23
      reference strain and identification of UDP-N-acetylglucosamine 4-epimerase].
AB  - Lipopolysaccharide (LPS) is one of the major components of the outer membrane of
      gram-negative bacteria. It is an amphipathic molecule composing of lipid A, a
      core oligosaccharide and an O-specific antigen. O-antigen, which is a repeat unit
      polysaccharide, is a major contribution to the antigenic variability of the
      bacterial cell surface. Genes involved in O-antigen biosynthesis are generally
      found to be clustered between the housekeeping genes galF and gnd on the
      chromosome of E. coli. E. coli O23 is one of the enterotoxigenic E. coli causing
      pediatric diarrhea in the developing world. The O-antigen gene cluster of E. coli
      O23 type strain was amplified by long-range PCR using primers based on galF and
      gnd and then sequenced. Except for galF and gnd, seven open reading frames were
      identified and assigned functions on the basis of their similarity to those from
      available databases. The seven genes include a UDP-N-acetylglucosamine 4
      epimerase gene (gne), the O-antigen polymerase gene (wzy), the O-antigen
      transferase gene (wzx) and four glycosyltransferase genes (orf2, orf4, orf5,
      orf6). The UDP-N-acetylglucosamine 4-epimerase (Gne) was identified by mutation
      and complementation complement tests. The structure of Gne was predicted by the
      homology modeling method, and the active sites were also analyzed. The
      phylogenetic and structural analysis showed that the Gne derived from the common
      ancestor with E. coli O23 Gne were UDP-GlcNAc/UDP-GalNAc epimerases. The specific
      DNA used for rapid molecular genotyping for E. coli O23 was also identified.

PMID- 17172014
TI  - [Construction and identification of rpoS gene inserted and fused in frame with
      the promoterless lacZ in Pseudomonas sp. M18].
AB  - With hybridization in situ and Southern blots, an Eco RI- Xho I DNA fragment of
      3.1 kb in length containing an rpoS gene and its flanking sequence was first
      cloned into pBluescript SK to generate pBLS by screening the genomic DNA library
      of Pseudomonas sp. M18. In order to identify the potential factors involved in
      rpoS gene expression and the regulatory mechanism of RpoS in strain M18, the rpoS
      gene was inserted and fused in frame with a promoterless and truncated lacZ gene,
      and a mutant named as M18SZ was then constructed through homologous
      recombination. Growth curves in KMB medium indicated that loss of RpoS made the
      mutant strain M18SZ more sensitive to alteration of some environmental factors.
      With detection and comparison of beta-galactosidase activities from both the wild
      type strain M18 and its derivative M18SZ cultivated in KMB medium respectively,
      it was found that the expression level of beta-galactosidase activities in the
      mutant M18SZ was high and could come to 480U. Expression of beta-galactosidase
      activities of the wild type strain M18 in KMB medium was not almost detected
      during its whole growth phase. With these results, it was confirmed that the rpoS
      gene did be fused in frame with the truncated lacZ gene in chromosome of the
      mutant M18SZ. Meanwhile, it is suggested that construction of a mutation, which
      is made with fusion in frame with the truncated lacZ gene, may be verified by
      detecting its beta-galactosidase activity, not using Southern blot or PCR.

PMID- 17172015
TI  - [Construction of an inducible and efficient expression-secretion shuttle vector
      of B. subtilis].
AB  - A new shuttle vector pSB which could replicate in both Escherichia coli and
      Bacillus subtilis was constructed by fusing the E. coli plasmid pSP72 with the B.
      subtilis plasmid pUB18. After the sacB promoter and signal peptide sequence of B.
      subtilis was inserted in the multiple cloning sites (MCS) of pSB, The recombinant
      plasmid was designated as pSBP. The alpha-amylase gene terminator of Bacillus
      licheniformis was inserted at the other end of the MCS, resulting in expression
      secretion plasmid pSBPT. After a positive control gene degQ of Bacillus pumilus
      was then cloned into pSBPT, and the inducible and efficient expression-secretion
      shuttle vector pSBPTQ was thus constructed. To identify the function and the
      necessary of sacB p. s., alpha-amylase terminator, and degQ in the expression of
      heterologous gene of pSBPT, the DNA fragment encoding for vasostatin I was cloned
      downstream of sacB p. s. of pSBP, pSBPT and pSBPTQ, and the resultant plasmid
      pSV, pSVT and pSVTQ were then transformed into B. subtilis strain DB1342. The
      transformants were screened on LB plates containing 10 microg/mL kanamycin. The
      positive transformants were separately grown on kanamycin containing 2 x MSR
      medium and sucrose was added to 2% final concentration for induction after 2h
      cultivation. The culture supernatant was used to run SDS-PAGE and Western blot.
      The results show that after induced by sucrose, very few recombinant Vasostatin I
      was expressed in DB1342(pSV), and recombinant Vasostatin I expressed in
      DB1342(pSVTQ) with the positive control gene degQ is more than in DB1342(pSVT)
      without degQ, suggesting that the Vasostatin I gene expression in pSVTQ was
      enhanced by degQ. Comparing the recombinant Vasostatin I in DB1342(pSVTQ) cells
      and its culture supernatant, the SDS-PAGE result show that most of the
      recombinant Vasostatin I was secreted into the culture supernatant and there is
      no Vasostatin in inclusion body, the secretion rate is about 90%. The result of
      plasmid stability test show that pSBPTQ maintains at 83% in B. subtilis after 40
      generations.

PMID- 17172016
TI  - [Isolation, identification and genome sequenceing of a rabbit hemorrhagic disease
      virus strain WHNRH].
AB  - The rabbit hemorrhagic disease virus (RHDV) is a single-stranded positive-sense
      RNA virus of the family Caliciviridae with a high morbidity and mortality rates
      of about 90% in adult rabbits. A strain of rabbit hemorrhagic disease virus named
      WHNRH was isolated and identified in the research. The genome of WHNRH was then
      sequenced. Primers were designed referring to the genome sequences of RHDV
      published in GenBank and a RACE was applied to get the 5' terminus sequences. The
      other terminus sequences of WHNRH was acquired referring to the genome's polyA
      structure of RHDV. The genome was amplified with RT-PCR. All the RT-PCR products
      were cloned into the pMD18-T vector and sequenced. The sequencing result
      indicated that the complete genome of RHDV isolated strain WHNRH was composed of
      7437nt (not including polyA of 3' terminus), the identities were between 89.4%
      and 97.1% compared with the published genome sequences of six RHDV strains. The
      ORF1 of the genome of WHNRH was between 10nt and 7044nt and a polypeptide with
      2344 amino acids was coded, the identities of nucleotide and amino acids
      sequences were 89.1% - 96.1% and 96.0% - 98.4% respectively compared with the six
      published RHDV strains. The ORF2 of the genome of WHNRH was between 7025nt and
      7378nt and a polypeptide with 177 amino acids was coded, the identities of
      nucleotide and amino acids sequences were all between 92.1% and 96.9% compared
      with the six published RHDV strains.

PMID- 17172017
TI  - [The construction of Thermotoga maritima endoglucanase Cel12B fused with CBD and
      the characterization of chimeric enzyme].
AB  - Thermotoga maritima is strictly anaerobic and extremely thermophilic bacteria.
      The endoglucanase found in T. maritima showed extremely high thermostability and
      considerable potential in industrial application. Endoglucanase (Tm) Cel12B is
      extracellular enzyme. Tm Cel12B did not contain a cellulose-binding domain
      (CBD)and lacked activity on crystalline cellulose. Tm XynA is composed of
      catalytic domain (CD) and cellulose-binding domain (CBD). As such, the gene of
      CBD from Tm XynA was fused at the carboxyl-terminus of Tm Cel12B and recombinant
      plasmid pET-20b- Cel 12B- CBD was obtained. The recombinant plasmid pET-20b- Cel
      12 B- CBD was transformed to E. coli JM109 (DE3), induced by IPTG. The properties
      of chimeric enzyme were determined. The chimeric enzyme displayed pH activity and
      stability profiles similar to those of parental enzyme with optimal pH 5.8. The
      optimal activity of the chimera was observed at 100 degrees C and the enzyme kept
      87% of original enzyme activity after incubated at 90 degrees C for 2h. A notable
      feature on substrate specificity is that the chimeric enzyme has the capacity to
      hydrolases crystalline cellulose.

PMID- 17172018
TI  - [Cloning and characterization of the gene encoding IMPDH of Streptococcus suis
      serotype 2].
AB  - Given the lack of effective vaccines to control Streptococcus suis infection and
      the lack of a rapid and reliable molecular diagnostic assay to detect its
      infection, S. suis serotype 2 was sequenced partly in an effort to identify
      important virulence factors. Two new open reading frames were found located
      between orf2 and mrp. One of new open reading frame (2738 - 3694) that encoded a
      polypeptide of 319 amino acid residues with a calculated molecular mass of
      33.5kDa was identified by Western blot. GenBank database search revealed that the
      derived amino acid sequence shared low homology with sequences of known function
      from other genes. Second structure was analyzed by InterPro, PHD, DNAstar
      software, the deduced protein had functional domains typical of IMP dehydrogenase
      (IMPDH). The PCR product of the open reading frame was transformed into E. coli
      BL21 and the fusion protein of 48kDa was expressed. The recombinant protein was
      reactive with serum from pigs experimentally infected with virulent strains of S.
      suis type 2, suggesting that the protein is immunogenic. IMPDH activity staining
      confirmed that the protein has IMPDH function and can catalyze the rate-limiting
      reaction of GTP biosynthesis, the NAD-dependent reduction of IMP into XMP. Flow
      cytometry (FCM) revealed that the protein had apparent effect on HEp-2 cell
      cycle.

PMID- 17172019
TI  - [Glucoamylase enhancement regulated by blue light in Aspergillus niger].
AB  - Regulation of glucoamylase production in photoinduced A. niger under blue light
      were investigated. The results showed that continuous illumination of blue light
      was effective in promotion of conidiation, leading to more glucoamylase
      production due to the need of sporulation in A. niger. It was clear that 36h-old
      mycelium grown in dark was in the developmental stage of formation of
      conidiophore stalk and was most sensitive to BL A. niger cultures exhibited some
      competence stage to respond to blue light over a period of 36 h when early
      conidiophore stalk formed in darkness, and photoinduction at this critical period
      resulted in relatively higher yield of glucoamylase. The fluence-response data
      generated with blue light indicated that the optimum fluence required for the
      photomorphogenetic response in A. niger was no less than 450 (mol/m2 x s) to
      saturate the photoinduction system. The amount of glucoamylase gene (G1)
      transcripts accumulated during illumination with blue light was more than that in
      total darkness, whereas the threshold for G1 induction during illumination with
      increased gradient light was higher than that exposed directly to light of
      constant fluence, indicating the existence of a light adaptation mechanism for
      glucoamyalse production in response to blue light. Nevertheless, both high and
      low light were able to promote glucoamylase producing. Furthermore, suppression
      subtractive hybridization experiment revealed that some respiratory chain redox
      enzymes in mitochondria including alternative oxidase as well as sulfhydryl
      oxidase participated the photoresponse in A. niger and consequently influenced
      the metabolism. The results support a possibility of designing strategies to
      improve glucoamylase yield by application of blue light.

PMID- 17172020
TI  - [Two-dimensional gel electrophoresis analysis of moderately halophilic bacterium
      Halobacillus dabanensis D-8T under hypoosmotic shock condition].
AB  - Halobacillus dabanensis D-8T was isolated from the saline deposits of Daban lake
      in Xinjiang of China, and is able to grow in complex medium containing 0.5% to
      25% salt. To figure out the survival mechanisms of Gram-positive moderately
      halophilic bacteria under hypoosmotic shock conditions, two-dimensional gel
      electrophoresis (2-DE) was carried out to investigate differential protein
      expression profiles of H. dabanensis D-8T in response to low osmotic challenge.
      The 2-D gels were stored as dry gels and their images were taken by ImageScanner
      and analyzed by Imagemaster 2D Platinum software. About 650 protein spots were
      detected in 2-D gel. Most of proteins were distributed in molecular mass of 17.5 
      66kDa and the range of isoelectric point 4.0 - 5.9. A total of 34 protein spots
      were found to alter their expression after strain D-8T was subjected to
      hypoosmotic shock from 20% to 0% salinity for 5 min and 50 min. Among them, the
      expression of 20 protein spots is up-regulated including 6 new protein spots,
      while that of 14 protein spots is down-regulated in answer to sudden osmotic down
      shift. Protein spots of interest were excised from the gels and digested by
      trypsin. By means of matrix-assisted laser desorption ionization-time of flight
      mass spectrometry (MALDI-TOF/MS) and MASCOT search engine, 4 up-regulated protein
      spots were identified with peptide mass fingerprint, and are similar to heat
      shock protein DanK, rod shape-determining protein, penicillin-binding protein
      (PBP-1A) and 5-enolpyruvoylshikimate-3-phosphate synthase, respectively.
      Noticeably, PBP-1A firstly was up-regulated after shock of 5 min but disappeared
      after shock of 50 min. This indicated that the strain activate a minor mechanism
      of peptidoglycan synthesis to compensate the major synthesis mechanism for cells
      survival through a down-shift challenge. In addition, this paper was the first
      report that heat shock proteins were up-regulated in response to sudden osmotic
      down-shift.

PMID- 17172021
TI  - [Selection and interaction of Ni2+ metal-binding peptides].
AB  - Ni2+ binding peptides were selected from phage random dodecapeptide library by
      metal affinity chromatography. After four rounds of biopanning, phage
      amplification and DNA sequencing, a group of peptide sequences were obtained.
      GenBank blast found no homogenous sequences, Clustal W analysis showed no motifs
      but they were really riched in histidines and contained di- or more
      histidines(his). Affinity assays of selected metal-binding phages for various
      metal-charged NTA resins and the experiments of E. coli suppression and
      detoxification gave positive results for Ni2+ binding peptides: strong affinities
      for Ni2+ were found for Ni2+ binding peptide displayed phages, as well as for
      other metals (Cu2+, Co2+, Zn2+, Cr2+, Cd2+); affinities of the binding peptides
      for Cu2+, Ni2+, Co2+ and Zn2+ were much higher than that of Cd2+ and Cr2+; in
      addition, Ni2+ binding peptides displayed phages had effects on E. coli as to
      enhance the tolerance and detoxification of E. coli for heavy metals when exposed
      to Ni2+ and Cd2+. The interactions of meal binding peptides for heavy metals were
      also disclosed by microscopic observation. The research offered great values for
      the study of the interaction between metals and peptides, as well as in other
      areas such as heavy metal bioremediation.

PMID- 17172022
TI  - [Screening of short peptides binding to StxB by phage-display library].
AB  - Under induction with 41 degrees C, pBV220-stxb/DH5alpha expressed the recombinant
      protein Shiga Toxin B Subunit (StxB), which was purified by centrifugation,
      salting out and ion exchange chromatography. As a target, the purified-protein
      coated ELISA plate was used to screen phages able to bind onto it from a random
      12-mer peptide library. After 4 rounds of affinity screening, a group of clones
      were isolated from the peptide library. ELISA assay detected their binding
      activity with the target. 27 clones showed the specific binding activity. The
      peptide sequences of these positive phage clones were analyzed. 16 of them had
      the same sequence named A6, 2 clones had the A9 sequence, and 3 clones had the A3
      sequence. To evaluate the neutralization effect of A6 phage, animal test was
      carried out. The Shiga Toxin was incubated with A6 phage clone, then used to
      attack the Balb/C mice. As a control, the toxin was incubated with negative
      phage. In the control group, no mice survived. Comparing with it, the survival
      rate of the mice in neutralization group could reach to a level of 33.3%. It
      showed that the toxicity of Shiga Toxin was partly inhibited. The A6 peptide
      could be developed as an inhibitor of Shiga Toxin to cure the diseases caused by
      Shiga Toxin.

PMID- 17172023
TI  - [Isolation and characterization of 4 benzene/toluene-degrading bacterial strains
      and detection of related degradation genes].
AB  - Four bacteria with the ability of benzene or toluene degradation were isolated
      from the active sludge of a life sewage treatment farm, two of which degraded
      benzene, and named B1 and B2; and other two degraded toluene, and named J2 and
      J6, respectively. Sequence analysis of 16S rDNA showed that strain B1 and J2
      belonged to Pseudomonas, and B2, J6 belonged to Acinetobacter. They all well
      adapted to the circumstances from 18 degrees C to 37 degrees C, 0% to 3% NaCl,
      and pH 7-10. The isolate J2 showed a high tolerance to organic solvent as it
      could grow well in the medium containing 70% (V/V) toluene, and degraded 92.4% of
      0.1% (V/V) toluene within 72 hrs in a medium with toluene as the sole carbon
      source; while J6 presented 84.8% degradation under the same conditions to
      toluene. In the case of B1 and B2, they degraded 67.7% and 94.2% of 0.1% (V/V)
      benzene within 72 hours, respectively. Moreover, all strains were detected
      harboring the same benzene dioxygenase gene. In addition, J2 and J6 also had
      toluene dioxygenase genes which share 86.5% homology from each other. These
      bacteria are of potential in bio-treatment of benzene and toluene pollutants.

PMID- 17172024
TI  - [16S rDNA-RFLP analysis of structure and diversity of an aerobic microbial
      community degrading hexachlorobenzene].
AB  - Hexachlorobenzene is a chlorinated aromatic hydrocarbon that was widely used as a
      seed dressing for prevention of fungal growth on crops, and is also a component
      of fireworks, ammunition, and synthetic rubbers. Because of the bioaccumulation
      and persistence of hexachlorobenzene as well as its potential toxicity,
      hexachlorobenzene must be removed from environment. The potential for aerobic
      dechlorination of hexachlorobenzene by a hexachlorobenzene-adapted mixed culture
      was investigated. An aerobic microbial community which was able to grow at the
      presence of hexachlorobenzene was enriched from sediment from contaminated site
      after incubating about 2 months. During the growth of the mixed microorganisms on
      hexachlorobenzene, the accumulating consumption of oxygen, the microbial
      population curve and the release of Cl- were investigated. The data suggest the
      rapid degradation of hexachlorobenzene to support microbial growth and the
      aerobic decholrination of hexachlorobenzene was observed. The result showed that
      the mixed microorganisms were able to utilize hexachlorobenzene as sole carbon
      and energy source. It was shown that up to 55% of HCB could be degraded during 18
      days incubation at 30 degrees C in mineral salts medium (pH 7.0) with 4.5mg/L
      HCB. The calculated rate of hexachlorobenzene biodegradation was 137.5 microg/ (L
      x d). The 16S rDNA genes were amplified from community DNA by using primers
      specific to bacteria and were subsequently cloned. The cloned 16S rDNA fragments
      were reamplified, and restriction analysis was performed following separate
      digestion with enzymes Hae III and Rsa I. Application of restriction fragment
      length polymorphism screening approach revealed 9 clusters, and 3 major clusters
      were sequenced. Nearly complete 16S rDNA sequence analysis show that the
      microbial community was dominated by Alcaligenes and Azospirillum groups. This is
      the first report describing aerobic dechlorination of hexachlorobenzene via
      dehalorespiration by a microbial community which was enriched from contaminated
      site. The microbial community can be used to degrade highly recalcitrant
      chlorinated pollutants.

PMID- 17172025
TI  - [Construction of a versatile degrading bacteria Pseudomonas putida KT2440-DOP and
      its degrading characteristics].
AB  - Triazophos is a kind of organophosphorous pesticide which was widely used by
      farmers all over the world in 1990's. It is effective in controlling pesticide
      but harmful to human beings. Bioremediation is an effective and economic method
      to treat environment that has been polluted by hazardous organic compounds, so
      researchers paid much attention in this area. Most of which focused on isolating
      functional bacteria, studying its degrading mechanism, and cloning degradation
      related genes. MP-4 was isolated from soil polluted by Triazophos for a long time
      and identified as Ochrobactrum sp.. The triazophos hydrolase (tpd) gene was
      cloned by the method of shotgun cloning, and the sequences were determined and
      analyzed. In the former tests it was found that there was only 18 base pairs
      different in tpd gene from mpd gene, which was isolated from methyl parathion
      degrading strain Pseudomonas putida DLL-1. Enzyme TPD can hydrolyze triazophos
      and methyl parathion while MPD cannot hydrolyze triazophos. Pseudomonas putida
      KT2440 is a metabolically versatile saprophytic soil bacterium that has been
      certified as a biosafety host for the cloning of foreign genes. This bacterium is
      known for its diverse metabolism and potential for development of biopesticides
      and plant growth promoters because of its ability to colonize rhizosphere of crop
      plants. Tpd gene was isolated from the genomic DNA of Ochrobactrum sp. MP-4 by
      PCR amplification. Recombinant plasmids pTPD was constructed by ligating tpd gene
      into broad host vector pBBRMCS-5. With the help of plasmid pRK2013, pTPD was
      transferred into Pseudomonas putida KT2440 to construct KT2440-DOP. KT2440-DOP
      can degrade many organophosphate pesticides and aromatics compounds. The specific
      activity of organophosphate hydrolase of KT2440-DOP was approximately 2 times of
      MP-4. Later, parameters affecting bioremediation of Organophosphate pesticide in
      soil using KT2440-DOP will be studied.

PMID- 17172026
TI  - [Composition diversity of lactic acid bacteria (LAB) community Al2 used for
      alfalfa silage].
AB  - Alfalfa is the most important forage grass that is difficult to ensile for good
      quality. Using silage inoculants are the important way for preservation of
      alfalfa silage. Through continuous restricted subcultivation, a lactic acid
      bacteria (LAB) community Al2 was selected from well-fermented alfalfa silage.
      Plate isolation and Denaturing Gradient Gel Electrophoresis (DGGE), construction
      of 16S rDNA clone library were used to identify the composition diversity of Al2
      community, with 7 strains detected, and they were all belonged to Lactobacillus.
      The composition ratios of the 7 strains were 55.21%, 19.79%, 14.58%, 3.13%,
      3.13%, 3.13%, 1.03% according to 16S rDNA clone library. Al2-1i, Al2-2i, Al2-3i,
      corresponding to L. plantarum (99.9%), L. kimchii (99.4%), L. farciminis (100%)
      were detected by plate isolation. Among 3 isolates, Al2-1i had the highest
      ability of dropping pH and producing lactic acid, and the amount of lactic acid
      was reach to 18g/L at 24h cultivated in MRS media. The ability of dropping pH and
      producing lactic acid of Al2-3i was the lowest. From DGGE profiles, the dominant
      strains in Al2 community were L. plantarum and L. kimchii. L. plantarum was
      detected during the whole process, and L. kimchii was detected in the later
      phase.

PMID- 17172027
TI  - [Activity and ecological distribution of actinomycetes from soil in the
      southeastern of Tibet].
AB  - The soil samples were collected from primeval forest, alpine meadow, marshy,
      grainfield and vegetable farmland ect. 9 different kinds of Vegetative type and
      from 2970 - 4590 altitude of southeastern of Tibet. The amount,composition,
      antimicrobial activity of mesophilic and psychrophilic actinomycetes and some
      mesophilic actinomycetes of physiological and biochemical characteristics were
      studied by normal methods. These actinomycetes were identified at genus level by
      their morphological properties. Results indicated that: (1) 9 genus of
      actinomycetes were isolated from soil and Actinosynnema was never reported in
      China. Grain field contains the largest quantity of actinomycetes. (2) Primeval
      forest contains the largest quantity of antimicrobal actinomycetes, so more and
      more antimicrobal actinomycetes information can be obtained from them. (3) The
      strains tested had stronger antimicrobial activity against Gram-positive bacteria
      than Gram-negative bacteria, had stronger antimicrobial activity against fungi
      than bacteria. (4) Many strains of streptomyces have some enzyme activities such
      as gelatin utilization, Milk-clotting enzyme etc.

PMID- 17172028
TI  - [Isolation, classification and antimicrobial activity of endophytic actinomycetes
      from plant leaves].
AB  - Leave samples of Paeonia lactiflora and Trifalium repens were collected from
      Sichuan Province and Beijing respectively to study their endophytic actinmycetes.
      After a well-established surface-sterilized procedure, the samples were plated on
      agar media of TWYE, HV, YECD, NA and WA, followed by incubation at 28 degrees C
      for 2 - 4 weeks. With the help of light microscope, 15 actinomycetes strains were
      isolated from the plates. Comparison of cultural features and fingerprinting
      analyses of BOX-PCR products were performed to cluster the isolates, with the
      result that all the strains were assigned to 12 different genotypes, half of them
      from Paeonia lactiflora and half from Trifalium repens. A combination of
      morphological and 16S rRNA gene sequence data showed that except strains C4 and
      C5, which belonged to Pseudonocardia, 13 of the isolates were streptomycetes.
      Most isolates share high 16S rRNA gene sequence similarities to known type
      strains. However, strain C12 shares low values, 96.6% in maximum, and strain C5
      shares 97.9% in maximum; more assays are needed to ascertain their taxonomic
      positions. In the tests of antimicrobial activity against 7 bacteria, 3 fungi and
      1 yeast, 11 isolates were positive in one or more tests, and 55% of the positive
      ones could inhibit the growth of Rhizoctonia solani, a significant pathogen of
      plants.

PMID- 17172029
TI  - [Cloning and identification of cellulase genes from uncultured microorganisms in
      pulp sediments from paper mill effluent].
AB  - The metagenomic DNA of pulp sediments from paper mill effluent was extracted and
      purified. The 16S rDNA was amplified using the purified metagenomic DNA as
      template and a 16S rDNA library was prepared. Sequence analysis of 16S rDNA
      clones showed that diverse of uncultured bacteria inhabit in this environment,
      which can be classified into 4 clusters as Spirochaetes, Proteobacteria,
      Bacteroidetes and Firmicutes. A metagenomic library containing 10000 clones was
      constructed into cosmid vector, and the capacity of inserted DNA of which was
      3.53 x 10(8) bp. Functional screening of the library resulted in isolation of two
      independent clones expressing endoglucanase activity, three independent clones
      expressing exoglucanase activity and two independent clones expressing beta
      glucosidase activity. One clone expressing strongest enzyme activity from each
      activity category was chosen to be further analyzed. Three novel cellulase genes
      designated as umcel5L, umcel5M and umbgl3D were identified by subcloning,
      sequencing and expression. The umcel5L encodes an endoglucanase belonging to
      glycosyl hydrolase family 5, which is most related to an endoglucanase from
      Bradyrhizobium japonicum at 43% identity and 59% similarity. The umcel5M encodes
      a cellodextrinase belonging to glycosyl hydrolase family 5, which is most similar
      to a cellodextrinase from Fibrobacter succinogenes at 48% identity and 69%
      similarity. The umbgl3D encodes a putative beta-glucosidase belonging to glycosyl
      hydrolase family 3, which shares highest homology with a beta-glucosidase from
      Thermotoga maritima at 46% identity and 61% similarity. It is the first time to
      reveal the bacterial diversity of pulp sediments from paper mill effluent and
      clone novel cellulase genes from the bacteria by culture-independent method.

PMID- 17172030
TI  - [Characterization of Salmonella typhimurium multidrug resistance and the reversal
      of antimicrobial resistance].
AB  - Salmonella typhimurium 17Y, isolated from one diseased pig that was clinically
      diagnosed as pig salmonellosis, was a multiresistance strain with resistance to
      14 antibiotics among tested 19 antibiotics. In this study, the resistance to 11
      antimicrobials was reversed by high temperature and high concentration (0.5%) of
      SDS, resulting in the sensitive strain 17S1. PCR results showed that the
      resistant genes BlaTEM, blaOXA-1, cat 1, tet (B), aacC2 located on the plasmid.
      Furthermore, PCR detected the class I integron which carries dhfrX II for
      trimethoprim resistance, aadA18b for aminoglycoside resistance and sull for
      sulfamethoxazole resistance. The integron was identified to exist in the plasmid.
      Because the target genes gyrA and parC for quinolone category were detected by
      PCR from both resistant and sensitive strains, it was determined that the genes
      gyrA and parC were located in the bacterial genome. The gene sequencing of gyrA
      and parC revealed that a point mutation AAC --> GAC resulting in one amino acid
      replacement of N87D in gyrA occurred for the sensitive strain 17S1. It was
      demonstrated that the amino acid 87 was a hot point for mutation in quinolone
      resistance determining region (QRDR). The finding suggests that the amino acid
      replacement of N87D is responsible for the quinolone susceptibility. In addition,
      the 100 continuous passages of the sensitive strain showed that the drug
      sensitive status was stable. However, when the drug pressure maintained for a
      long time, the resistance was induced again. Meanwhile, 6 salmonella plasmid
      virulence genes (spvA-D, R and rck) were eliminated with the resistance reversal,
      indicating that the virulence plasmid was cured. Reasonably, the bacterial
      virulence decreased shown by 10- fold increase of LD50 for the sensitive strain,
      and the statistical significant decline of in vivo spread and growth (P < 0.05)
      in mice. Taken altogether, the multidrug resistance of Salmonella typhimurium was
      determined by its plasmid. The plasmid elimination with SDS reversed most of the
      resistance (11/14) and decreased the bacterial virulence. Therefore, strategy to
      eliminate the plasmids would be an effective way to deal with the multiresistance
      issue. However, drug control in routine clinical practice would not be neglected
      at any time.

PMID- 17172031
TI  - [Protective immune response of guinea pigs against challenge with foot and mouth
      disease virus by immunization with foliar extracts from transgenic tomato plants
      expressing the FMDV structural protein VP1].
AB  - The plant constitutive expression vector pBin438/VP1 for VP1 gene of foot-and
      mouth disease virus strain O/ China/99 was constructed. Mediated with
      Agrobacterium tumefaciens GV3101 harboring pBin438/VP1, VP1 gene was transferred
      into cotyledons of tomato. After selected by Kanamysin, sixty resistant lines
      were obtained. The integration and transcription of the VP1 gene in transformed
      plants was detected by PCR and RT-PCR. After being detected by sandwich-ELISA
      assays, about 40% transformed plants confirmed to express the recombinant
      protein. The leave extracts of two positive lines were respectively emulsified in
      Freund's adjuvant and guinea pigs were intramuscular inoculation at days 0, 15
      and 30d. According to the sera antibody levels and the protection of the
      vaccinated guinea pigs against challenge with 100ID50 FMDV, probed into the
      immunogenicity of the target protein expressed in transgenic plants. Experimental
      results showed that the plant expression vector was successfully constructed. PCR
      and RT-PCR analyses confirmed VP1 gene was transformed into tomato plants and got
      expression at the transcription levels. The expressed VP1 protein of FMDV, which
      was identified by ELISA and Western blot, can be specifically recognized by
      polyclonal antibodies against FMDV. Indirect-ELISA antibody titers reached 1:64
      twenty-one days after the third inoculation. In the challenge test, the
      protection against FMDV challenge in two groups was 80% and 40% respectively. The
      immunization test in guinea pigs indicated that the expression product of
      transgenic tomato plants had immunogenicity and could effectively induce the
      specific antibodies against FMDV.

PMID- 17172032
TI  - [Inhibition of IFN-gamma receptor signaling by hepatitis C virus non-structural
      protein NS4B].
AB  - The function of NS4B is incompletely understood. The aim of the study is to
      understand the influence of NS4B on anti-viral response. After cell line stably
      expressing NS4B established, the influence of IFN-alpha of different
      concentration on VSV was studied using plaque assay; cell expression profiling
      caused by NS4B was studied using DNA microarray, and the IFNGR1 fluorescence
      intensity was analyzed. Our data showed that HCV-NS4B could suppress immuno
      associated gene expression, in particular, IFN-gamma receptor signal transduction
      related genes. Taken together, NS4B could play some roles in HCV resistance to
      IFN therapy.

PMID- 17172033
TI  - [Expression of inducible nitric oxide synthase was regulated by activating
      nuclear factor kappaB in mouse macrophages stimulated with ureaplasma urealyticum
      lipid-associated membrane proteins].
AB  - The aim was to investigate the molecular mechanisms responsible for the inducible
      nitric oxide synthase (iNOS) gene expression stimulated by lipid associated
      membrane proteins (LAMPs) of Ureaplasma urealyticum (Uu). Mouse macrophages were
      stimulated by Ureaplasma urealyticum LAMPs to analyze the production of nitric
      oxide (NO) and the expression of iNOS detected by RT-PCR and Western blot. The
      activation of NF-kappaB was examined in mouse macrophages treated with LAMPs by
      indirect immunofluorescence (IFA), immunocytochemistry and Western blot. The
      effects of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB and of
      cycloheximide (CHX), a protein synthase inhibitor, on the expression of iNOS and
      on the activation of NF-kappaB were also investigated in mouse macrophages
      treated with LAMPs. Results showed Ureaplasma urealyticum LAMPs stimulated mouse
      macrophages to express iNOS and thus produce NO in dose- and time-dependent
      manners by activating nuclear factor kappaB. The activation of NF-kappaB and the
      expression of iNOS were inhibited by LAMPs combination with PDTC or CHX. In
      conclusion, these findings suggested Ureaplasma urealyticum may be an important
      pathogenic factor due to the ability of LAMPs to stimulate the expression of
      iNOS, which is probably medicated by the activation of NF-kappaB.

PMID- 17172034
TI  - [The immune enhancement of the C3 to the Escherichia coli vaccine].
AB  - C3b was separated and purified from the SPF chicken serum. It was linked with E.
      coli antigen by the glutaral. 11 days aged SPF chicken were immunized by the
      complex antigen and the chickens of control group were immunised by the FCA- E.
      coli antigen . They were boosted at the age of 18 day. The immune response was
      monitored by an enzyme-linked immunosorbent assay(ELISA) for anti-E. coli
      anitibody. The ELISA results indicated that during the early several weeks, IgG
      titers elicited by FCA (FCA-E. coli) were higher than those elicited by C3 (C3b
      E. coli), but decreased rapidly after a peak around the end of 4th week from
      being immunized. Chickens immunized with C3b always gave increased response, and
      the IgG titers were equal to that of FCA at the end of 5th week from being
      immunized and then higher and higher than that of FCA. Thus the adjuvant effect
      of C3b is different from that of FCA, it could induce production of memory cell
      and make the antigens stimulate immune cells consistently and stably.

PMID- 17172035
TI  - [Studies on the breeding by ion implantation and cultivation of mycophenolic acid
      producing strain].
AB  - Mycophenolic acid is produced by aerobic fermentation of several Penicillium
      species. It has a broad spectrum of activity like antitumor activity, antiviral,
      anti-psoriatic, immunosuppressive and anti-inflammatory activity. It also
      exhibits antibacterial and antifungal activities. The immunosuppressive effect of
      MPA has been important in treatment of organ rejection after organ transplant
      surgery. There is a continuous need to find improved process for efficiently
      obtaining superior MPA producing mutants. In recent years, the ion implantation
      technique has been widely applied in many fields and has been drawn morn concern.
      However there is no report in the field of mutational breeding of MPA producing
      strain. Penicillium brevicompactum M-51 was derived from MPA producing strain F
      663 by varied mutational methods including U.V. and microwave irradiation. In the
      process of increasing the production of MPA from P. brevicompactum M-51, a mutant
      strain M-163 was obtained by means of N+ ion implantation. An decline-increase
      decline tendency of strain survival rates was observed when the strain was
      implanted by N+ ion with dose from 20 2.6 x 10(13) ions/cm2 to 180 x 2.6 x 10(13)
      ions/cm2 under implantation energy 15 keV. It apparently appeared "saddle shape".
      And under the implantation dose of 140 x 2.6 x 10(13) ions/cm2, the variation
      rate and the positive variation rate of the strain had reached the highest values
      88.9% and 63.4%, respectively. The HPLC results showed that MPA yield of P.
      brevicompactum M-163 was improved by 30.1%, and its productivity was rather
      stable through successive transfer of cultures. The effect of seed growth time on
      yield of MPA was studied, and the best seed age was 24h after incubation. In the
      mean time, the fermentative condition of M-163 was studied through orthogonal
      design. The major ingredients being investigated included carbon and nitrogen
      sources. Finally the optimized fermentation medium was obtained. The yield of MPA
      reached 2819g/mL in the optimized submerged fermentation progress. In conclusion,
      N+ ion implantation had been proven to be effective for mutational breeding of P.
      brevicompactum M-51. By means of N+ ion implantation and optimizing the
      fermentative condition, the yield of MPA was increased by 20.2 times than the
      wild-type stain F-663.

PMID- 17172036
TI  - [Characterization of hydrogen peroxide production by a novel oral streptococci,
      S. oligofermentans isolated from human oral cavity].
AB  - High level of hydrogen peroxide was produced by S . oligofermentans, a novel oral
      streptococcus isolated from human oral cavity previously in our laboratory. To
      characterize the hydrogen peroxide production by S. oligofermentans, hydrogen
      peroxide yields at different growth phases and from different substrates were
      assayed. The results turned out that hydrogen peroxide production started at the
      beginning of logarithmic phase, and reached the maximal yield at the early
      stationary phase. Peptone and yeast extract could be the main substrates for
      hydrogen peroxide production. Moreover, lactate, as a fermentative product of
      glucose, can be another substrate for hydrogen peroxide production. Furthermore
      three oxidases activities possibly associated with H2O2 production were assayed,
      and both activities of lactate oxidase and NADH oxidase were detected under
      aerobic condition, while pyruvate oxidase activity was not detected in the
      permeabilized cells of S. oligofermentans, implying that S. oligofermentans could
      mainly rely on the two enzymes activities for H2O2 production.

PMID- 17172037
TI  - [Properties of a triphenylmethane dyes decolorization enzyme (TpmD) from
      Aeromonas hydrophila strain DN322].
AB  - A novel bacterial enzyme for decolorization of triphenylmethane dyes from
      Aeromonas hydrophila strain DN322 was purified and named TpmD. The basic
      properties of this enzyme including molecular weight, isoelectric point Km as
      well as the optimum temperature and pH were determined and the enzyme was
      identified as an NADH/NADPH-dependent oxygenase in previous research. Based on
      previous results, the effect of different inhibitor including Vc, metyrapone,
      rotenone, antimycin A and NaN3 as well as the effect of FAD and FMN on the
      activity of TpmD were measured. The results indicated that the activity of the
      decolorization enzyme was inhibited by Vc and metyrapone in a concentration
      dependent manner, but wasn't inhibited by rotenone, antimycin A and NaN3. The
      activity of the decolorization enzyme was not enhanced by addition of FAD or FMN.
      The solution of the enzyme protein displayed only a single peak at 408nm in the
      Soret region, a characteristic peak of porphyrin, but did not show the
      characteristic peak of the cytochrome P450 proteins at 450nm in sodium dithionite
      (DTN)-reduced enzyme solution after treatment with carbon monoxide. The amino
      acid sequence of N-terminal of TpmD provided further evidence that the enzyme is
      an oxygenase. All these results suggest that decolorization enzyme TpmD is a new
      hemo-containing oxygenase. The decolorization enzyme would be a good material for
      further research of the enzymological mechanism of triphenylmethane dyes
      decolorization by bacteria.

PMID- 17172038
TI  - [Expression of a thermostable a-amylase mutant into Escherichia coli and Pichia
      pastoris].
AB  - Alpha-amylase are of considerable commercial value. It can be produced by a wide
      variety of microorganisma. The alpha-amylase gene (amyE) from Bacillus
      licheniformis, which is widely used for the industrial hydrolysis of starch, was
      mutated (amyEM), then amplified by PCR and inserted into pBV220 and pPIC9k to
      obtain the recombinant vector pBV220-amyEM and pPIC9k-amyEM. These recombinant
      vectors were transformed into corresponding competent cell E. coli DH5alpha and
      P. pastoris GS115 respectively. The resulting recombinant strains,
      DH5alpha/pBV220-amyEM and GS115/ pPIC9k-amyEM, were then screened by measuring
      the enzymatic activity and SDS-PAGE. DH5alpha/pBV220-amyEM was induced by
      temperature and GS115/pPIC9k-amyEM by methanol. In contrast to the parent cells,
      the a-amylases were expressed in both the recombinant strains. In E. coli the
      molecular weight was approximately 55kDa; optimal temperature and pH of the
      recombinant a-amylase were 80 degrees C - 90 degrees C and 6.0 respectively. The
      recombinant amylase had high activity in pH 5.0 - 5.5 compared to wild type. In
      Pichia pastoris, the recombinant amylase was secreted to the medium; molecular
      weight was 60kDa for the putative post-translational modifications; optimal pH
      shifted to 5.5. The specific activities of alpha-amylase produced by E. coli and
      P. pastoris were 8.1U/mg and 102U/mg respectively. This result indicated that the
      alpha-amylase were secreted into the culture medium with high efficiency in the
      recombinant P. pastoris High activity in high temperature and lower pH properties
      impart the recombinant amylase potential applications in industry.

PMID- 17172039
TI  - [Expression and purification of membrane immunogens of Treponema pallidum in
      Pichia pastoris].
AB  - Genes of Treponema pallidum subsp. pallidum three membrane antigens (47kDa, 17kDa
      and 15kDa) were amplified by PCR with the template of the genomic DNA of Nichols
      strain and cloned into plasmid pPICZ B, the recombinant plasmids of pTP47, pTP17
      and pTP15 were transformed into Pichia pastoris GS115. Recombinant antigens were
      expressed by the methanol induction and confirmed by the Western blot assay.
      Fusion antigens with 6 x His tag were purified using Ni-NTA agarose, and purified
      fusion protein yields were 4.8mg/L, 6.6mg/L and 25mg/L of cell culture for His
      TP15, His-TP17 and His-TP47, respectively. Purity of all three antigens were more
      than 96% by SDS-PAGE assay. Particularly, His-TP17 was more about 6kDa molecular
      weight than that of expected probably because of glycosylation in Pichia
      pastoris. At last, these recombinant antigens were evaluated by ELISA assay with
      serum from syphilis patient and healthy blood donors, all three antigens showed
      strong sensitivity and specificity. So three membrane antigens of Treponema
      pallidum were expressed and purified fused with 6 x His tag in Pichia pastoris
      for the first time. The immunoreactivity results showed that all of which can be
      applied to diagnosis of Treponema pallidum, especially to diagnosis method based
      on combined two or three antigens.

PMID- 17172040
TI  - [Expression and purification of Rv3369 of Mycobacterium tuberculosis].
AB  - To obtain purified recombinant Rv3369 protein by means of expressing the Rv3369
      protein of Mycobacterium tuberculosis in E. coli. The gene coding Rv3369 protein
      was amplified by polymerase chain reaction (PCR), then was inserted into an
      expression vector pET28a to get recombinant plasmid. The recombinant plasmid was
      transformed into E. coli BL21(DE3) and induced by IPTG. The expressed product was
      indentified by SDS-PAGE and purified by Ni- NTA His. Bind Resin. The sequence of
      Rv3369 in recombinant plasmid was the same with GenBank's report. The molecular
      mass of the product is 19.5kDa, which accounts for about 20% in the thalli
      proteins, and its purity is more than 90% analyzed by SDS-PAGE and laser
      scanning. The yield of recombinant protein is 1.56mg from 100mL of culture.
      Compared with other methods, purity of the recombinant protein is higher through
      affinity chromatography.

PMID- 17172041
TI  - [Analysis and research of the proteins for the wild type and the rough type of
      Salmonella typhi by 2D-PAGE].
AB  - To find out the protein properties of the wild type and the rough type of
      Salmonella typhi (S. typhi); to probe the genetic mechanism of the rough
      variation of S. typhi. The proteins were separated from the wild type and the
      rough type of S. typhi, and then the samples were processed by 2D-PAGE and
      stained by Coomassie Brilliant R-250. The properties and relationship of the
      protein patterns were analyzed by the software Imagemaster 6.0. By the 2D-PAGE,
      the similar protein patterns with 78% Sd (similar data) would be found between
      the wild type and the rough type of S. typhi. The distribution of most protein
      spots was in the range of pH 3.0 - 6.4 where the molecular weight of protein was
      smaller than 30kDa. According to the characters of differential proteins, there
      is not only the polysaccharide side chain of the O antigen but also some proteins
      that could be lost or changed in the rough strain of S. typhi. Most proteins in
      it would be the same as those in the parental bacteria so that the characteristic
      protein pattern of Salmonella can be found by 2D-PAGE. This property is useful
      for analysis and identification of the homologue between variations and their
      parental bacteria.

PMID- 17172042
TI  - [Expression of the VP2 gene of chicken infectious anemia virus in E. coli and
      analysis of immunogenicity].
AB  - The coding region of VP2 gene from Chicken Infectious Anemia was amplified from
      genome extracted from chicken liver tissue by PCR. PCR product was double
      digested with restriction enzymes BamH I and Sal I and cloned into pET-28a
      digested with BamH I and Sal I. Subsequently, the recombinant plasmid pET-28-VP2
      was extracted and double digested with restriction enzymes BamH I and Sal I.
      After confirming its rightness by PCR and analysis of restriction endonucleases,
      the recombinant plasmid pET-28-VP2 was transformed into E. coli BL21 (DE3)
      strain. The culture was induced by 1 mmol/L IPTG at 37 degrees C for three hours
      and analyzed with SDS-PAGE. The result shows that gene encoding VP2 of CIAV was
      expressed successfully in E. coli and the fusion protein existed in supernatant,
      which was about 31kDa and showed specific immunoreactivity with anti-CIAV sera in
      Western blot. The fusion protein was purified by Ni2+ -affinity chromatography
      and quantitated by Bradford method. Then BALb/c mice were immunized with purified
      protein emulsified with Freund's complete adjuvant on day 0 and boosted twice on
      day 14 and 28 with the same dose of antigens emulsified with Freund's incomplete
      adjuvant, respectively. The serum isolated were examined by an enzyme-linked
      immunosorbant assay (ELISA) using the purified VP2 and CIAV as coating antigens
      and the serum could react with target protein and CIAV in ELISA detection test.

PMID- 17172043
TI  - [Study progress on the mechanism of heterotrophic nitrification].
AB  - Nitrification plays an important role in the nitrogen cycle. Autotrophic bacteria
      have traditionally been regarded as the nitrifying agents. However, research in
      last few decades has established that a lot of heterotrophic microorganisms also
      make contribution to nitrification. Heterotrophic nitrification has become an
      issue for scientific research and environment management. In this overview, both
      the location of heterotrophic microorganisms and the methods of detection and
      isolation which take the polyphyletic nature of heterotrophic bacteria into
      account are briefly presented. The study on the mechanism which focuses on the
      enzymes, functional genes, electron transfer and metabolism pathway of
      heterotrophic nitrification are mainly reviewed. In the end, the problems lying
      in the research of the mechanism of the heterotrophic nitrification are proposed
      and future research directions are suggested.

PMID- 17172044
TI  - [Research on mangrove soil microorganisms: past, present and future].
AB  - Special Mangrove soil niches possesses valuable microbial resources.
      Unfortunately, up to the present, so far there is very little knowledge on the
      mangrove soil microbial communities. It mainly due to the limitations of research
      methods. Cultureindependent approaches based on 16S rRNA, 18S rRNA gene analysis
      open the window to study microbial diversity in mangrove soil. The progress had
      achieved about studying on mangrove soil microbial species diversity, metabolic
      diversity and treating environmental pollutions was summarized in the paper. In
      addition, the bright future of mangrove soil microorganisms was described.

PMID- 17172045
TI  - [Listeria-induced host cellular actin cytoskeleton rearrangement and
      phospholipase D].
AB  - Either phagocytosis of macrophage to pathogen or pathogen-induced invasion into
      non-professional phagocytes, such as epithelial cells, require actin cytoskeletal
      rearrangements and remodeling of the plasma membrane, which are regulated
      precisely by monogeric GTPase and the correlated proteins. As a key signaling
      molecule in the cell, phosphotidicphospholipase D (PLD) regulates or interacts
      directly with cellular actin cytoskeleton rearrangement. Phospholipase D plays an
      important role in FcgammaRI and C-reactive protein-mediated phagocytosis and
      phosphorylated cofilin, a ADF (actin depolymerizing factor) is able to bind to
      phospholipase D and stimulate it; meanwhile, the Listeria-induced actin
      cytoskeleton rearrangement during the infection is controlled by the
      phosphorylation of cofilin. Thus, it made challenge to disclose the function of
      PLD on the regulation of Listeria-induced actin cytoskeleton rearrangement during
      infection, furthermore, it may provide us more understanding on the role of PLD
      in the infection and inflammation, which is essential to dissect the molecular
      mechanism of bacterial-host interaction more thoroughly.

PMID- 17172046
TI  - [The application and research advances of Brucella vaccines].
AB  - Brucellosis is a crucial zoonosis caused by Brucella, which has some traits of
      wide hosts, great infectivity and difficulty in cure. Brucellosis caused great
      losses to farming and people's health. Vaccination is the main measure used to
      control Brucellosis, and some attenuated Brucella strains were often used as
      vaccines. To find more effective vaccines, Scientists are now constructing
      recombinant strains, DNA vaccines and subunit vaccines, as well as inducing new
      attenuated strains from isolations. The present applications of B. abortus strain
      19 (S19) , B. melitensis Rev. 1 (Rev. 1), B. suis strain 2 (S2), B. abortus
      strain 45/20 (45/20) and rough strain B. abortus 51 (RB51) were discussed. And
      some recent research work on Brucella vaccines, such as Brucella recombinant
      vaccines, DNA vaccines and so on, were reviewed in this paper.

PMID- 17172047
TI  - Cloning, expression and function of phosphate transporter encoded gene in Oryza
      sativa L.
AB  - OsPT6:1, a phosphate transporter encoding gene from the leaf samples of Oryza
      sativa, was identified through PCR with specifically designed primers. The
      phylogenetic analysis and the conserved amino acid residue site detection
      suggested OsPT6:1 a possible high-affinity phosphate transporter encoding gene.
      In situ hybridization and RT-PCR demonstrated the expression of OsPT6:1 in both
      roots and leaves. The peak expression signal was observed in mesophyll cells
      under low phosphorus (P) induction. A homologous recombination study indicated
      that OsPT6:1 can enhance the Pi uptake efficiency of Pichia pastoris. At the
      meantime, the introduction of OsPT6:1 was able to complement the Pi uptake
      function of yeast cells with high-affinity phosphate transporters deficient.
      Those results substantiated our contention that OsPT6:1 encoded a high-affinity
      phosphate transporter of Oryza sativa.

PMID- 17172048
TI  - Adapting rice anther culture to gene transformation and RNA interference.
AB  - Anther culture offers a rapid method of generating homozygous lines for breeding
      program and genetic analysis. To produce homozygous transgenic lines of rice
      (Oryza sativa L.) in one step, we developed an efficient protocol of anther
      callus-based transformation mediated by Agrobacterium after optimizing several
      factors influencing efficient transformation, including callus induction and
      Agrobacterium density for co-cultivation. Using this protocol, we obtained 145
      independent green transformants from five cultivars of japonica rice by
      transformation with a binary vector pCXK1301 bearing the rice gene, Xa21 for
      resistance to bacterial blight, of which 140 were further confirmed by PCR and
      Southern hybridization analysis, including haploids (32.1%), diploids (62.1%) and
      mixoploids (7.5%). Fifteen diploids were found to be doubled haploids, which
      accounted for 10.7% of the total positive lines. Finally, by including 28 from
      colchicine induced or spontaneous diploidization of haploids later after
      transformation, a total of 43 doubled haploids (30.7%) of Xa21 transgenic lines
      were obtained. We also generated two RNAi transgenic haploids of the rice OsMADS2
      gene, a putative redundant gene of OsMADS4 based on their sequence similarity, to
      investigate its possible roles in rice flower development by this method. Flowers
      from the two OsMADS2 RNAi transgenic haploids displayed obvious homeotic
      alternations, in which lodicules were transformed into palea/lemma-like tissues,
      whereas identities of other floral organs were maintained. The phenotypic
      alternations were proved to result from specific transcriptional suppression of
      OsMADS2 gene by the introduced RNAi transgene. The results confirmed that OsMADS2
      is involved in lodicule development of rice flower and functionally redundant
      with OsMADS4 gene. Our results demonstrated that rice anther culture could be
      adapted to gene transformation and RNAi analysis in rice.

PMID- 17172049
TI  - Expression of NAC1 up-stream regulatory region and its relationship to the
      lateral root initiation induced by gibberellins and auxins.
AB  - A 1050 bp up-stream regulatory fragment of the transcription factor gene NAC1 in
      Arabidopsis thaliana was isolated using polymerase chain reaction (PCR) based
      techniques. The fragment was used to substitute the 35S promoter of the pBI121
      plasmid to construct a beta-glucuronidase gene (GUS) expression system. The
      construct was introduced into tobacco (Nicotiana tabaccum) plants by the
      Agrobacterium-mediated transferring method. GUS expression pattern was studied by
      using the transgenic lines. The results showed that the GUS driven by the NAC1 up
      stream regulatory region was specifically expressed in the root meristem region,
      basal areas of the lateral root primordium and the lateral roots. The GUS
      expression was induced by 3-indolebutyric acid (IBA) and gibberellins (GA3 and
      GA4+7). The results indicated that the up-stream regulatory fragment of NAC1
      responded to plant hormones. The fragment might be involved in both auxins and
      gibberellins signaling in promoting the development of lateral roots.

PMID- 17172050
TI  - Heterologous expression of the AtDREB1A gene in chrysanthemum increases drought
      and salt stress tolerance.
AB  - DNA cassette containing an AtDREB1A cDNA and a nos terminator, driven by a
      cauliflower mosaic 35S promoter, or a stress-inducible rd29A promoter, was
      transformed into the ground cover chrysanthemum (Dendranthema grandiflorum) 'Fall
      Color' genome. Compared with wild type plants, severe growth retardation was
      observed in 35S:DREB1A plants, but not in rd29A:DREB1A plants. RT-PCR analysis
      revealed that, under stress conditions, the DREB1A gene was over-expressed
      constitutively in 35S:DREB1A plants, but was over-expressed inductively in
      rd29A:DREB1A plants. The transgenic plants exhibited tolerance to drought and
      salt stress, and the tolerance was significantly stronger in rd29A:DREB1A plants
      than in 35S:DREB1A plants. Proline content and SOD activity were increased
      inductively in rd29A:DREB1A plants than in 35S:DREB1A plants under stress
      conditions. These results indicate that heterologous AtDREB1A can confer drought
      and salt tolerance in transgenic chrysanthemum, and improvement of the stress
      tolerance may be related to enhancement of proline content and SOD activity.

PMID- 17172051
TI  - Comparative studies on histological and ultra-structure of the pituitary of
      different ploidy level fishes.
AB  - The histological and ultra-structure of the pituitary in diploid red crucian carp
      (Carassius auratus red var.), triploid crucian carp and allotetraploid hybrids
      within and after the breeding season were comparatively studied. The result
      showed that there were six endocrine cell types in the pituitary of these three
      kinds of fishes, and there was an obvious difference in cell size among different
      ploidy level fishes. As for the same type of pituitary cells, the cell size was
      increased gradually with the increasing ploidy level. In the breeding season, the
      allotetraploid hybrids had higher proportion of gonadotropin cells (GTH) than
      triploids, and the triploids had higher proportion of GTH than diploids. The
      results were related to the earlier sexual maturity of allotetraploid hybrids and
      sterility of triploid crucian carp. On the other hand, among the three kinds of
      fishes, the proportion of somatotropin (STH) cells in triploids crucian carp was
      the highest, whereas that in allotetraploid hybrids was the lowest. The results
      might be connected with the faster growth rate of triploids and slower growth
      rate of allotetraploid hybrids. In addition, in GTH cells of meso-adenohypophysis
      after the breeding season, there were many endocrine particles in triploids,
      while those endocrine particles were released from the cells in allotetraploids
      and diploids. This result showed that the sterility of triploid crucian carp
      might be related to the hormone which was not released from the GTH cells. In a
      word, the present study indicated that the differences in the structure of
      pituitary among different ploidy level fishes contributed to their difference in
      the growth rate and gonadal development.

PMID- 17172052
TI  - Gene expression profile in immunologically injured liver cell of mice.
AB  - To study the gene expression profiles between immunologically injured liver cell
      and normal liver cell of mice and to screen on a large scale the differentially
      expressed genes associated with the formation of liver injury, the experimental
      mice were randomly divided into the normal group for controlling and the
      immunologically liver-injured group induced by BCG and LPS. The liver mRNA of the
      two groups were extracted respectively and reversely-transcribed to cDNA with the
      incorporation of different fluorescence (Cy3, Cy5) labeled dUTP as the
      hybridization probes. The mixed probes were hybridized to the cDNA microarray
      chips. The fluorescent signal results were acquired by scanner ScanArray 4000 and
      analyzed with software GenePix Pro 3.0. Among the 14112 target genes, 293 genes
      were found to be significantly differentially expressed, in which 188 genes were
      up-regulated and 105 genes were down-regulated. Based on the analysis of
      biological functions of those differentially expressed genes, it was indicated
      that the occurrence and development of mouse liver damage induced by BCG and LPS
      were highly correlated with the processes of immune reactions, cell synthesis,
      metabolism, apoptosis and transportation in liver cell, which might be quite
      important for elucidating the regulatory network of gene expression associated
      with the liver damage, also important for finally discovering the pathogenic
      mechanisms of immunological liver damage.

PMID- 17172053
TI  - Identification of a denitrifying bacterium and verification of its anaerobic
      ammonium oxidation ability.
AB  - A strain D3 of denitrifying bacterium was isolated from an anammox reactor, and
      identified as Pseudomonas mendocina based on the morphological and physiological
      assay, Vitek test, Biolog test, (G + C) mol% content, and 16S rDNA phylogenetic
      analysis. As a typical denitrifying bacterium, strain D3 achieved the maximal
      nitrate reduction rate of 26.2 mg/(L x d) at the nitrate concentration of 88.5 mg
      N/L. The optimal pH and growth temperature were 7.84 and 34.9 degrees C,
      respectively. Strain D3 was able to oxidize ammonia under anaerobic condition.
      The maximum nitrate and ammonium utilization rates were 6.37 mg/(L x d) and 3.34
      mg/(L x d), respectively, and the consumption ratio of ammonia to nitrate was
      1:1.91. Electron microscopic observation revealed peculiar cell inclusions in
      strain D3. Because of its relation to anammox activity, strain D3 was presumed to
      be anammoxosome. The present investigation proved that denitrifying bacteria have
      the anammox ability, and the results have engorged the range of anammox
      populations.

PMID- 17172054
TI  - Group I but not group II NPV induces antiviral effects in mammalian cells.
AB  - Nucleopolyhedrovirus (NPV) is divided into Group I and Group II based on the
      phylogenetic analysis. It has been reported that Group I NPVs such as Autographa
      californica multiple NPV (AcMNPV) can transduce mammalian cells, while Group II
      NPVs such as Helicoverpa armigera single NPV (HaSNPV) cannot. Here we report that
      AcMNPV was capable of stimulating antiviral activity in human hepatoma cells
      (SMMC-7721) manifested by inhibition of Vesicular Stomatitis virus (VSV)
      replication. In contrast, the HaSNPV and the Spodoptera exigua multiple NPV
      (SeMNPV) of group II had no inhibitory effect on VSV. Recombinant AcMNPV was
      shown to induce interferons alpha/beta even in the absence of transgene
      expression in human SMMC-7721 cells, while it mediated transgene expression in
      BHK and L929 mammalian cells without an ensuing antiviral activity.

PMID- 17172055
TI  - Study on interaction between microtubule associated protein tau and prion
      protein.
AB  - Microtubule-associated protein tau is considered to play roles in many
      neurodegenerative diseases including some transmissible spongiform
      encephalopathies. To address the possible molecular linkage of prion protein
      (PrP) and tau, a GST-fusion segment of human tau covering the three-repeat region
      and various PrP segments was used in the tests of GST pull-down and
      immunoprecipitation. We found tau protein interacted with various style prion
      proteins such as native prion protein (PrPc) or protease-resistant isoform
      (PrPSc). Co-localization signals of tau and PrP were found in the CHO cell
      tranfected with both PrP and tau gene. The domain of interaction with tau was
      located at N-terminal of PrP (residues 23 to 91). The evidence of molecular
      interactions between PrP and tau protein highlights a potential role of tau in
      the biological function of PrP and the pathogenesis of TSEs.

PMID- 17172056
TI  - Expression of Pdx-1 in bone marrow mesenchymal stem cells promotes
      differentiation of islet-like cells in vitro.
AB  - Bone marrow mesenchymal stem cells (BMSCs) have the ability of self-renewal and
      multi-directional differentiation. Recent reports showed that BMSCs could
      differentiate into endocrine cells of pancreas. However, the differentiation is
      not efficient enough to produce insulin-producing cells for the future
      therapeutic use. Pdx-1 is a crucial regulator for pancreatic development.
      Therefore we constructed a eukaryotic expression vector containing Pdx-1 to
      determine the effect of Pdx-1 expression on differentiation of BMSCs in vitro.
      The results showed that BMSCs could self-assemble to form functional pancreatic
      islet-like structures after differentiation in vitro. The proportion of insulin
      producing cells differentiated from Pdx-1+BMSCs was 28.23% +/- 2.56%, higher than
      that from BMSCs transfected with vacant vector and Pdx-1-BMSCs (7.23% +/- 1.56%
      and 4.08% +/- 2.69% respectively) by flow cytometry. Immunocytochemical
      examination also testified the expression of multiple beta-cells-specific genes
      such as insulin, glucagons, somatostatin in differentiated BMSCs. The results
      also revealed that the expressions of genes mentioned above in Pdx-1+BMSCs were
      higher than that in Pdx-1-BMSCs, which was confirmed by Western blotting analysis
      and RT-PCR. Glucose-induced insulin secretion from Pdx-1+BMSCs in 5 mmol/L and 25
      mmol/L glocuse was (56.61 +/- 4.82) microU/mL and (115.29 +/- 2.56) microU/mL
      respectively, which were much higher than those from Pdx-1-BMSCs ((25.53 +/-
      6.49) microU/mL and (53.26 +/- 7.56) microU/mL respectively). Grafted animals
      were able to maintain their body weight and survive for relatively longer periods
      of time than hyperglycemic sham-grafted controls, which demonstrated an overall
      beneficial effect of the grafted cells on the health of the animals. These
      findings thus suggested that exogenous expression of Pdx-1 should provide a
      promising approach for efficiently producing islet-like cells from BMSCs for the
      future therapeutic use in diabetic patients.

PMID- 17172057
TI  - Construction and characterization of an HCV-derived multi-epitope peptide antigen
      containing B-cell HVR1 mimotopes and T-cell conserved epitopes.
AB  - Hepatitis C (HCV) genome is highly variable, particularly in the hypervariable
      region 1 (HVR1) of its E2 envelope gene. The variability of HCV genome has been a
      major obstacle for developing HCV vaccines. Due to B-cell HVR1 mimotopes
      mimicking the antigenicity of natural HVR1 epitopes and some T-cell epitopes from
      the consensus sequence of HCV genes conserving among the different HCV genotypes,
      we synthesized an minigene of HCV-derived multi-epitope peptide antigen (CMEP),
      which contains 9 B-cell HVR1 mimotopes in E2, 2 conserved CTL epitopes in C, 1
      conserved CTL epitope in NS3 and 1 conserved Th epitope in NS3. This minigene was
      cloned into a GST expression vector to generate a fusion protein GST-CMEP. The
      immunogenic properties of CEMP were characterized by HCV infected patients' sera,
      and found that the reactivity frequency reached 75%. The cross reactivity of anti
      CEMP antibody with different natural HVR1 variants was up to 90%. Meanwhile, we
      constructed an HCV DNA vaccine candidate, plasmid pVAX1.0-st-CMEP carrying the
      recombinant gene (st) of a secretion signal peptide and PADRE universal Th cell
      epitope sequence in front of the CMEP minigene. Immunization of rabbits with
      pVAX1.0-st-CMEP resulted in the production of antibody, which was of the same
      cross reactivity as the fusion protein GST-CMEP. Our findings indicate that the
      HCV-derived multi-epitope peptide antigen in some degree possessed the
      characteristics of neutralizing HCV epitopes, and would be of the value as a
      candidate for the development of HCV vaccines.

PMID- 17172058
TI  - Heat shock response and mammal adaptation to high elevation (hypoxia).
AB  - The mammal's high elevation (hypoxia) adaptation was studied by using the
      immunological and the molecular biological methods to understand the significance
      of Hsp (hypoxia) adaptation in the organic high elevation, through the mammal
      heat shock response. (1) From high elevation to low elevation (natural hypoxia):
      Western blot and conventional RT-PCR and real-time fluorescence quota PCR were
      adopted. Expression difference of heat shock protein of 70 (Hsp70) and natural
      expression of brain tissue of Hsp70 gene was determined in the cardiac muscle
      tissue among the different elevation mammals (yak). (2) From low elevation to
      high elevation (hypoxia induction): The mammals (domestic rabbits) from the low
      elevation were sent directly to the areas with different high elevations like
      2300, 3300 and 5000 m above sea level to be raised for a period of 3 weeks before
      being slaughtered and the genetic inductive expression of the brain tissue of
      Hsp70 was determined with RT-PCR. The result indicated that all of the mammals at
      different elevations possessed their heat shock response gene. Hsp70 of the high
      elevation mammal rose abruptly under stress and might be induced to come into
      being by high elevation (hypoxia). The speedy synthesis of Hsp70 in the process
      of heat shock response is suitable to maintain the cells' normal physiological
      functions under stress. The Hsp70 has its threshold value. The altitude of 5000 m
      above sea level is the best condition for the heat shock response, and it starts
      to reduce when the altitude is over 6000 m above sea level. The Hsp70 production
      quantity and the cell hypoxia bearing capacity have their direct ratio.

PMID- 17172059
TI  - Seroprevalence of mumps, varicella and rubella antibodies in children 1-16 years
      of age in eastern Turkey.
AB  - In this study, seroprevalence of mumps, varicella and rubella was investigated in
      803 unvaccinated children in eastern Turkey whose ages ranged between 1 and 16
      years. Mumps IgG, varicella IgG and rubella IgG antibody levels in all children
      were studied by enzyme-linked immunosorbent assay (ELISA) method. Information
      regarding socioeconomic characteristics, number of siblings and disease history
      was gathered for each participant. No significant difference in seropositivity
      was detected between girls and boys. Seroprevalence of mumps increased with age,
      with a seropositivity rate of 29.9% in children aged 1-4 years and of 88.8% in
      those aged 13-16 years. Seroprevalence of varicella increased with age, with a
      seropositivity rate of 26.8% in children aged 1-4 years and of 90.3% in those
      aged 13-16 years. Seroprevalence of rubella also increased with age, with a
      seropositivity rate of 47.3% in the children aged 1-4 years and of 89.2% in those
      aged 13-16 years. There was a statistically significant increase in the rate of
      seropositivity with advancing age through the group of 13-16 years old (p <
      0.05). In conclusion, in order to avoid mumps, varicella and rubella diseases and
      their possible complications, children should be vaccinated against these three
      diseases before the age of two, since seroprevalence increases with age.

PMID- 17172060
TI  - The prevalence of atopy in children with antibodies against hepatitis A virus and
      hepatitis B virus.
AB  - To investigate the relationship between atopy and hepatitis A virus (HAV) and
      hepatitis B virus (HBV) infections, we studied 42 children who had had HAV
      infection (Group I), 28 children who had had HBV infection (Group II), and 31
      children who were seronegative for both HAV and HBV infection (Control group).
      Serological tests for HAV and HBV infections (anti-HAV IgG, HBsAg, anti-HBc IgG)
      and allergic skin tests and specific IgE investigations for the detection of
      atopy were carried out. In this study, there was no significant divergence in the
      socio-demographic characteristics among the three groups. The rates of specific
      IgE positivity in children in the HAV seropositive group (11.9%) and in children
      in the HBV seropositive group (17.8%) were lower than in the control group
      (35.4%) (p = 0.03 and p = 0.22, respectively). Also, the number of children with
      respiratory allergic diseases (allergic rhinitis and/or asthma) both in the HAV
      seropositive group and in the HBV seropositive group were significantly lower
      than in the control group (p < 0.05). When atopy in all of the groups was
      evaluated, the prevalence of atopy was found to be more widespread in HAV
      seronegative children (Adjusted OR, 9.2; 95% CI, 1.7-48.2) and HBV seronegative
      children (Adjusted OR, 5.9; 95% CI, 1.1-31.8) than in HAV and HBV seropositive
      children, after adjustment for age, number of older siblings and education of the
      father. In conclusion, in this study, the prevalence of atopy in children who had
      had HAV or HBV infection was found to be low, and this situation was considered
      to be related to the relationship of HAV and HBV infections to poor hygiene and
      to the fact that these infections occur at early ages in Turkey.

PMID- 17172061
TI  - Tracing immature myelin in acute disseminated encephalomyelitis.
AB  - Inherent abnormalities of myelin have been suggested in the pathogenesis of
      multiple sclerosis (MS). We investigated myelin in acute disseminated
      encephalomyelitis (ADEM) patients by magnetic resonance spectroscopy (MRS) and
      cerebrospinal fluid (CSF) analysis for citrulline, a marker of immature myelin. A
      citrulline peak was observed in the normal appearing white matter of 7/15
      patients and of 1/10 age-matched neurological controls (p=0.08). CSF citrulline
      was elevated in 4/6 patients. Alterations in the composition of myelin might
      predispose to or follow acute inflammatory disorders of the central nervous
      system.

PMID- 17172062
TI  - The effects of anticancer drugs on levels of nitric oxide and adrenomedullin.
AB  - Nephrotoxicity is one of the most important complications of anticancer
      treatment. Ifosfamide, platinum and methotrexate (MTX) affect renal tubular
      epithelial cells. Nitric oxide (NO) serves many functions within the kidney.
      Adrenomedullin (AM) is a potent vasodilator peptide, and may function as a
      circulating hormone and an autocrine/paracrine mediator involved in the
      regulation of the cardiovascular system, blood pressure, and renal function. It
      also has a renoprotective effect and inhibits the generation of reactive oxygen
      metabolites. To our knowledge, no studies have investigated the effects of
      anticancer drugs on levels of AM and NO. We investigated the effects of these
      drugs on the levels of AM and total nitrite, a stable product of NO, and their
      relations to renal functions. The study was performed in 18 patients (13 males, 5
      females) who received chemotherapeutic regimens including high-dose MTX or
      ifosfamide and platinum. Total nitrite was quantitated by means of the Griess
      reaction, while AM level was measured by high performance liquid chromatography
      (HPLC). Plasma total nitrite level (micromol/L) was decreased after chemotherapy
      (78.73 +/- 47.28 vs. 46.69 +/- 13.89, p: 0.002). A statistically significant
      difference was found between fractional excretion (FE) of total nitric oxide
      (FE(NO)) before and after chemotherapy (25.89 +/- 23.11 vs. 51.74 +/- 40.01, p:
      0.008). The differences in plasma AM levels (pmol/ml) before (25.07 +/- 4.98) and
      after (30.20 +/- 1.39) chemotherapy were also statistically significant (p:
      0.005). FE(AM) after chemotherapy (1.41 +/- 1.01) was found to be higher than
      before chemotherapy (0.64 +/- 0.43) (p: 0.000). Our results indicate that some
      chemotherapeutic agents (high-dose MTX, ifosfamide, and cisplatinium) may cause
      renal tubular damage. FE(AM) and FE(NO) may also be used for the detection of
      subclinical acute tubular nephrotoxicity. However, further detailed researches
      will be necessary to establish the certain role of NO and AM in toxicities of
      chemotherapeutic agents.

PMID- 17172063
TI  - A different type of cardiomyopathy: ventricular noncompaction (evaluation of 8
      cases).
AB  - Ventricular noncompaction, characterized by numerous, prominent ventricular
      trabeculations and deep intratrabecular recesses, is thought to be due to an
      arrest of myocardial morphogenesis. We report eight patients with ventricular
      noncompaction diagnosed at our center in the previous one year. Two patients had
      associated congenital cardiac anomalies while the others were without coexisting
      cardiac abnormalities. Both ventricles were involved in one patient, only the
      right ventricle in one, and only the left ventricle in six patients. Seven
      patients had initially been diagnosed as having different types of
      cardiomyopathies. In conclusion, based on our limited experience, we propose that
      during the differential diagnosis of cardiomyopathies, ventricular noncompaction
      should be considered.

PMID- 17172064
TI  - Nonbronchoscopic bronchoalveolar lavage for diagnosing ventilator-associated
      pneumonia in newborns.
AB  - The appropriate treatment of ventilator-associated pneumonia (VAP) must be based
      on accurate diagnosis, which can be done by microbiological examination of the
      samples obtained from the respiratory tract by nonbronchoscopic bronchoalveolar
      lavages (NB-BAL). This study was designed to determine the effectiveness of NB
      BAL in diagnosing VAP in newborns. Two hundred and seven NB-BAL samples were
      obtained from 145 intubated neonates for microbiologic and cytologic evaluation
      of the distal airway. The NB-BAL samples were processed for microscopic
      quantification of the polymorphonuclear cells (PMN) containing intracellular
      bacteria (ICB) and quantitative culture (positive threshold, 10(5) cfu/ml). VAP
      was defined as a new, progressive, or persistent (>24 hrs) infiltrate on the
      chest radiograph, with two or more of the following criteria: (a) macroscopically
      purulent tracheal secretions, (b) fever or hypothermia, (c) leukocytosis or
      leukopenia, and (d) worsening of respiratory status with a Pa O2/F IO2 ratio of
      <240. Colonization was defined as mechanical ventilation for more than seven
      days, no signs of infection, and isolation of the same bacteria species in two
      previously obtained NB-BAL samples. Of the 145 neonates, 40 (27.5%) were infected
      and 12 (8.3%) were colonized. Forty-four patients (30%) developed VAP according
      to diagnostic categories based on clinical and radiologic criteria. Forty
      newborns with VAP (90%) had positive NB-BAL culture. The sensitivity,
      specificity, and positive and negative predictive values of NB-BAL fluid culture
      for VAP diagnosis were 90%, 90%, 70%, and 97%, respectively. The percentage of
      ICB was significantly higher in newborns with VAP. The presence of ICB in 2% or
      more on Giemsa-stained smears corresponded to a sensitivity of 94%, specificity
      of 83%, positive predictive value of 94%, and negative predictive value of 83%.
      The sensitivity and specificity of combination of ICB and NB-BAL quantitative
      culture in diagnostic samples were 94% and 90%, respectively. The positive and
      negative predictive values were 71% and 98%. In our study, the presence of
      leukocytes in the NB-BAL fluid smear of infants with VAP was higher than that of
      the colonized babies (84%, 26%). This difference was statistically significant (p
      < 0.0001). The sensitivity and specificity of PMNs in NB-BAL fluid for the
      diagnosis were 86% and 75%, respectively, and the positive and negative
      predictive values were 89% and 69%. We conclude that NB-BAL lavage is well
      tolerated and clinically useful in mechanically ventilated newborns. These
      results suggest that NB-BAL fluid microscopic examination and cultures can offer
      a sensitive and specific means to diagnose VAP in newborns and may provide
      relevant information about the causative pathogens.

PMID- 17172065
TI  - Can renal doppler sonography replace diuretic radionuclide renography in infants
      with hydronephrosis?
AB  - Reliable differentiation between obstructive and non-obstructive hydronephrosis
      is decisive for the further therapeutic management in infants. The results of
      renal Doppler sonography were compared with diuretic radionuclide renography and
      with the follow-up results in 33 patients (range: 21 to 98 days). In Doppler
      sonography, a resistive index (RI) of > 0.9 was considered to be abnormal in the
      sense of an obstruction. In diuretic renography, a T1/2 value (time until a 50%
      decrease in activity in the kidneys was observed after injection of furosemide)
      of >20 min was appraised as obstructive hydronephrosis. In six patients an
      obstructive (T1/2 >20 min) and in 27 patients a non-obstructive (T1/2 <20 min)
      hydronephrosis was found. All patients with obstruction in diuretic renography
      showed an abnormal RI (>0.9) in Doppler sonography. In addition, all patients
      with surgery and obstruction in diuretic radionuclide renography showed an
      improvement in hydronephrosis. However, seven patients had a false-positive
      result in Doppler sonography. All patients with non-obstruction in diuretic
      radionuclide renography showed no worsening of hydronephrosis without surgery in
      the follow-up. We found a RI of 0.84 +/- 0.07 in the non-obstructive group and of
      0.96 +/- 0.05 (p = 0.018) in the obstructive group. Doppler sonography showed
      discrepant results compared to diuretic radionuclide renography and therefore
      cannot replace this method.

PMID- 17172066
TI  - Evaluation of low-dose hCG treatment for cryptorchidism.
AB  - The aim of this study was to evaluate the efficiency of low-dose hCG (human
      chorionic gonadotropin) (500 IU/week for 3 weeks) in the treatment of
      cryptorchidism and in the assessment of Leydig cell functions. We include 35 male
      patients who had been diagnosed with cryptorchidism by the pediatric
      endocrinology specialist in the study. Twenty-one cases (Group I) received 500
      IU/week of hCG while 14 patients (Group II) received 1500 IU/m2 three times a
      week, both for three weeks. The percentage of testis descent was calculated for
      both groups for the right and left testes. Leydig cell functions were evaluated
      by the pre- and post-treatment measurement of plasma testosterone level in all
      cases. A delta testosterone greater than 100 was considered to be a sufficient
      response. Among our patients, 77% had unilateral and 23% bilateral
      cryptorchidism. Unilateral cryptorchidism was detected in 80.9% of Group I
      patients and 71.4% of Group II patients. The pre-treatment percentages for Group
      I of right- and left-sided cryptorchidism were 81% and 38.1%, respectively, which
      decreased to 23.8% and 9.5% after treatment. The pre-treatment percentages for
      Group II of right- and left-sided cryptorchidism were 57.1% and 71.4%,
      respectively, which decreased to 14.3% and 35.7% after treatment. The success
      rate of hCG treatment, as defined by the testis descending into the scrotum, was
      66.7% for Group I and 57.1% for Group II (p > 0.05). There was no significant
      difference between the two groups when Leydig cell functions were assessed. In
      conclusion, it is possible to use low-dose hCG for the treatment of
      cryptorchidism and the assessment of Leydig cell functions.

PMID- 17172067
TI  - Frequency and characteristics of mongolian spots among Turkish children in Aegean
      region.
AB  - Mongolian spots, which are benign congenital lesions observed in the first years
      of life, can cause distress for parents due to aberrant localization as well as
      unexpected number and size. Therefore, efficient differential diagnosis is
      necessary. The aim of this study was to determine the frequency and
      characteristics of mongolian spots in 1-12-month-old children in a west Anatolian
      city and to evaluate parental approach to these lesions. The study included 924
      children who presented to Ege University Hospital Healthy Child Outpatient
      Department between January and August 2003. A questionnaire was applied to the
      families while all children were examined scrupulously for the presence of
      mongolian spots. The frequency of these lesions in the study population was
      determined to be 26%; this rate was 20% and 31% in boys and girls, respectively.
      No lesion was detected in blond-haired children; however, it was detected in 47%
      of brunettes. Most common localizations were lumbosacral, gluteal, and back,
      though knee, scalp and feet were also encountered. Upon questioning, most parents
      stated it was a birth mark; however, 10% accepted to consult a doctor about the
      issue. In conclusion, identifying mongolian spots and informing parents are
      essential to strengthen the family-doctor relationship.

PMID- 17172068
TI  - Prevalence and distribution of children with congenital heart diseases in the
      central Anatolian region, Turkey.
AB  - Congenital heart diseases (CHD) are the most frequent malformation at birth. The
      aims of this study were to assess the prevalence of congenital heart disease,
      their different types, and the detection rate among children in the central
      Anatolian region in Turkey. The study was conducted during an eight-year period
      (March 1995-December 2002). The prevalence of CHD in a large tertiary care
      hospital in the central Anatolian region in Turkey was studied. The diagnosis of
      a structural defect was based on echocardiographic study. The following age
      groups were considered: neonates, infants and toddlers, preschool children,
      schoolchildren, and adolescents. In the study period, 1,693 children were found
      to have CHD; 1253 patients were neonates and infants. Total prevalence of CHD
      over the study period was 7.77 per 1000 live-born. The prevalence increased from
      6.35 to 9.65 per 1000 live births between 1995 and 2002 (p < 0.05). The average
      age at diagnosis was 2.2 +/- 3.64 years (1 day to 18 years, median 5 months).
      There were 863 (51%) boys and 830 (49%) girls, with a male/female ratio of 1:1.
      Isolated ventricular septal defect (32.6%) was the most frequent acyanotic
      anomaly, and tetralogy of Fallot (5.8%) was the most frequent cyanotic anomaly.
      The commonest non-cardiac anomalies with CHD were musculoskeletal anomalies. Down
      syndrome was determined in 83 patients (78.3%) from all syndromic CHD cases.
      Congenital heart disease is a very significant health problem. It requires urgent
      measures in terms of organization of early diagnosis and proper management. The
      prevalence rate is comparable to that of similar developed countries. Increasing
      incidence of CHD might be attributed to more diagnoses with new technologic
      development or it may indicate a real increase in the defects.

PMID- 17172069
TI  - Steroid-induced psychosis in an adolescent: treatment and prophylaxis with
      risperidone.
AB  - Steroid-induced psychotic disorder is one of the serious adverse effects of
      corticosteroid therapy and is characterized by hallucinations and delusions.
      While the mechanism is unclear, treatment of steroid psychosis involves dosage
      reduction or discontinuation of prednisone. In cases where this cannot be done,
      typical treatment involves an antipsychotic medication. Although it is a well
      known complication in adulthood, literature about steroid-induced psychotic
      disorder in children and adolescents is lacking. Here we report a 12-year-old
      case of steroid-induced psychotic disorder who was treated with an atypical
      antipsychotic, risperidone, and in whom the antipsychotic therapy was maintained
      because of continuation of her corticosteroid treatment for nephrotic syndrome.
      Pediatricians should be aware of this rare problem when prescribing
      corticosteroids in this age group. To our knowledge, this is the first reported
      case of steroid-induced psychosis successfully treated with risperidone in an
      adolescent with nephrotic syndrome.

PMID- 17172071
TI  - Successful bone marrow transplantation in an 8-month-old patient with chronic
      granulomatous disease.
AB  - An eight-month-old boy with chronic granulomatous disease (CGD) received HLA
      identical sibling bone marrow transplantation (BMT) following busulphan and
      cyclophosphamide conditioning. No graft-versus-host disease was demonstrated.
      Five years after transplantation, mixed chimerism was 60% in peripheral blood,
      and 85% of his neutrophils had normal oxidative burst activity. He is now six
      years old, in very good health and growing well. In this period, he experienced
      no severe infectious diseases. To our knowledge, this is the first case of CGD
      who had BMT in Turkey. His successful outcome illustrates that BMT in a patient
      with CGD in the first years of life should be considered early if an HLA-matched
      donor is already available, before development of any recurrent life-threatening
      infections or irreversible organ damage.

PMID- 17172070
TI  - Use of bisphosphonates for resistant hypercalcemia in children with acute
      lymphoblastic leukemia: report of two cases and review of the literature.
AB  - Hypercalcemia is a rare complication of malignancy in children. We present two
      children, one of whom is the youngest reported, with CALLA+ B-cell acute
      lymphoblastic leukemia (ALL) who developed hypercalcemia at the time of diagnosis
      and were treated with relatively low-dose (0.5 mg/kg) intravenous pamidronate
      successive to conventional therapy. No major side effects were encountered except
      transient hypocalcemia and hypophosphatemia, which were easily managed by
      replacement therapy. Bisphosphonate therapy was found to be beneficial for the
      treatment of resistant hypercalcemia associated with ALL, even at relatively low
      doses.

PMID- 17172072
TI  - Primary hydatid cyst of the thigh: a case report of an unusual localization.
AB  - The sartorius muscle is a rare location of primary hydatid cyst. In this report,
      the clinical, pathologic, and radiologic features are discussed, with special
      emphasis on the pathologic and radiographic features. We report a case of hydatid
      cyst of the proximal thigh in an eight-year-old girl. Magnetic resonance (MR)
      images revealed muscular hydatid cyst in the sartorius muscle, with a striking
      appearance of daughter cysts. We did not find any visceral organ involvement.
      Wide excision was performed without destroying the cyst wall. Primary muscular
      hydatidosis should be kept in mind in the differential diagnosis of a cystic mass
      of a skeletal muscle.

PMID- 17172073
TI  - A patient with cystinosis presenting transient features of Bartter syndrome.
AB  - A 16-month-old boy was admitted to the clinic because of vomiting and growth
      failure. His weight and height measurements were under the fifth percentile. He
      had fair hair and skin, enlarged wrists and rachitic rosaries. The presence of
      metabolic alkalosis, hypokalemia, hypochloremia, and high renin and aldosterone
      levels were suggestive of Bartter syndrome. However, in view of the growth
      failure, fair hair and skin, proteinuria, polyuria and active rickets, cystinosis
      was considered. Bone marrow smear examination was normal, despite the existence
      of suspicious crystals in the cornea. Cystine crystals were seen in the
      conjunctiva biopsy and increased leukocyte cystine level was measured; therefore,
      definitive cystinosis diagnosis was made. Renal Fanconi syndrome with metabolic
      acidosis is prominent in cystinosis; however, in rare instances, if sodium
      dependent trans-tubular transport defect is present, patients could have Bartter
      syndrome findings such as hypochloremic metabolic alkalosis. Our case is a good
      example demonstrating that metabolic alkalosis should not exclude cystinosis and
      the other signs and symptoms of the patient should be thoroughly evaluated.

PMID- 17172074
TI  - Dorfman-Chanarin syndrome: a case with hyperlipidemia.
AB  - Dorfman-Chanarin syndrome is a rare, autosomal recessive disorder characterized
      by congenital ichthyosis and presence of intracellular lipid droplets in most
      tissues. Here, we present a patient from Turkey, who is the fourth Turkish case
      in the literature with this syndrome, and we review the previous reported cases.
      He was also the second case reported with hyperlipidemia.

PMID- 17172075
TI  - Acute hemorrhagic edema of infancy: a case report.
AB  - Acute hemorrhagic edema of infancy is a cutaneous leukocytoclastic vasculitis,
      clinically characterized by the acute development of peripheral edema and
      targetoid purpuric lesions on the face and extremities. The clinical picture has
      a violent onset with a short benign course followed by spontaneous complete
      recovery. We describe a five-month-old boy with acute hemorrhagic edema, in whom
      the disease appeared after antibiotic treatment for a cellulitis in front of the
      tragus.

PMID- 17172076
TI  - Spontaneous regression of left upper lobe emphysema after division of large
      ductus arteriosus in an infant.
AB  - Congenital lobar emphysema is cause of infantile respiratory distress and
      diagnosed by lobar overaeration, mediastinal shift and/or compression of the
      adjacent lobe. However, concomitant congenital heart disease with this clinical
      condition is not uncommon, and there is no uniform consensus about the treatment
      strategy in these particular cases. We present a child who was treated with
      division of large patent ductus arteriosus without the lobectomy.

PMID- 17172077
TI  - A 13-year-old female with Turner syndrome and achalasia.
AB  - The most common gastrointestinal problems associated with Turner syndrome are
      intestinal telangiectasia, colon carcinomas, inflammatory bowel, and liver
      diseases. In this paper we present for the first time a 13-year-old female with
      45,X karyotype associated with achalasia. As far as we know, achalasia associated
      with Turner syndrome has not been reported previously. The aim of this report was
      to point out the association of Turner syndrome and achalasia. It could be a
      coincidental or Turner syndrome-associated finding.

PMID- 17172078
TI  - Concurrent septic arthritis and urinary tract infection in a patient with
      nephrocalcinosis and vesicoureteral reflux.
AB  - An eight-month-old boy who presented with a 15-day history of vomiting was
      revealed to be suffering from urinary tract infection and nephrocalcinosis caused
      by vitamin D intoxication. During the treatment of vitamin D intoxication
      (alendronate, 5 mg/day), he developed urinary tract infection and septic
      arthritis of the left hip joint. Escherchia coli was isolated from his blood,
      urine, and joint fluid culture. He was operated, joint drainage was performed and
      appropriate intravenous antibiotic treatment was given for four weeks. After
      discharge, a voiding cystoureterogram revealed grade 4 vesicoureteral reflux in
      the right ureter. Combination of complex urinary anomalies associated with
      stagnation of urine flow and altered urinary dynamics, and metabolic urinary
      anomalies, such as hypercalciuria/nephrocalcinosis, may facilitate the occurrence
      of rare systemic complications of urinary tract infection.

PMID- 17172079
TI  - This is not your mentors' NIH--new strategies for research support.

PMID- 17172080
TI  - Congenital adrenal hyperplasia and poverty.

PMID- 17172081
TI  - Thyroid-associated ophthalmopathy in juvenile Graves' disease--clinical,
      endocrine and therapeutic aspects.
AB  - Children have about the same risk (or slightly increased) as adults to develop
      Graves' ophthalmopathy (GO) once they have contracted Graves' hyperthyroidism.
      The severity of childhood GO appears to be less than that of adult GO. The female
      preponderance is similar between children and adults with Graves' hyperthyroidism
      (87% and 83%, respectively), but the prevalence of smoking is much lower in
      children than in adults (4% and 47%, respecttively). Smoking is a risk factor for
      GO, and the odds increase significantly with increasing severity of GO. It has
      also been shown that the manifestation of GO begins to resemble the adult
      findings more closely when adolescence approaches. This could be explained by
      increasing smoking prevalence with age. A recent study supports the above data
      and provides a very interesting clue: the difference might be caused by exposure
      to tobacco smoke. Regarding treatment of thyroid eye disease (TED) in childhood,
      most physicians who are dealing with such cases prefer a 'wait-and-see' policy.
      Pharmacological intervention, predominantly with steroids, is considered
      appropriate in case of worsening of eye changes or no improvement of eye changes
      when the patient has become euthyroid. Doses between 5 and 20 g prednisone daily
      are used depending on the severity of the case. It has to be kept in mind that
      prolonged prednisone administration, which should be used in some severe cases of
      TED, is associated with weight gain, immune suppression and growth failure in
      children. Recently, it has been shown that somatostatin analogs (SM-as) might be
      of therapeutic value in the treatment of active TED in adults. However, initial
      studies were uncontrolled, non-randomized, and included only small numbers of
      patients. In the past 2 years, three double-blind, placebo-controlled clinical
      studies have been published, which have demonstrated only a modest improvement in
      proptosis. The current range of SM-a drugs target two of five somatostatin
      receptors present in the orbital tissues of TED patients. Therefore, there is a
      reason to believe that newer generations of SM-as that target a wider range of
      somatostatin receptors may show markedly superior results in the treatment of
      TED. Retrobulbar irradiation, which has proved beneficial in adults with TED, has
      no place in the treatment of juvenile GO, in view of the theoretical risk of
      tumor induction. The same applies to orbital decompression.

PMID- 17172082
TI  - Living with congenital adrenal hyperplasia in Vietnam: a survey of parents.
AB  - OBJECTIVE: Congenital adrenal hyperplasia (CAH) has the potential to place an
      enormous burden on families in resource-poor countries, and the aim of this
      survey was to provide more specific insights into the difficulties faced by
      families living with CAH in Vietnam. It is hoped that this information will be
      used to ensure that future efforts to reduce the burden of CAH are as effective,
      sustainable and appropriate as possible. DESIGN AND METHODS: A questionnaire
      based needs assessment survey was offered to parents of children with CAH who
      were attending the Annual CAH Support Group Meeting held at the National Hospital
      of Pediatrics (NHP) in Hanoi, Vietnam, on 10th June 2005. RESULTS: Fifty-three
      families responded to the questionnaire. Information pertaining to the purchase
      and use of medication to treat CAH, access to medical care, surgical treatment
      for girls, and a wide range of parental concerns was collected. CONCLUSIONS: This
      survey highlights the heavy burden that CAH places on families in Vietnam, and
      provides significant insights into various initiatives that could well help ease
      this suffering. In particular, efforts must be made to ensure essential
      medication is affordably available, communication of important messages to
      parents is enhanced, local support groups encouraged, and early diagnosis and
      medical treatment of CAH optimized so as to reduce morbidity and mortality.

PMID- 17172083
TI  - Osteopenic effects of MgSO4 in multiple pregnancies.
AB  - OBJECTIVE: To describe the effects of prolonged maternal treatment with MgSO4 in
      infants who were products of multiple pregnancies. STUDY DESIGN: Case series of
      infants presenting with osteopenia secondary to MgSO4 administration for preterm
      labor. RESULTS: Ten premature infants with hypermagnesemia (4.5+/-0.2 mg/dl),
      hypocalcemia (6.0 +/-0.3 mg/dl), and high serum alkaline phosphatase (574+/-96
      U/l) underwent imaging studies that showed diffuse osteopenia of the long bones
      and probable rib fractures. All mothers had isolated premature labor, for which
      they were given MgSO4; (average dose 3.66+/-0.08 kg/ pregnancy over 10.0+/-0.5
      weeks). On follow-up (to 9 months), all infants had complete or near complete
      resolution of the osteopenia. CONCLUSIONS: Premature infants who are exposed to
      large doses of MgSO4, especially those of multiple pregnancies, have an increased
      risk of developing hypocalcemia, osteopenia, and fractures. Our findings indicate
      that these infants should be identified at birth and managed prospectively.

PMID- 17172084
TI  - Pre-operative differentiation of pediatric ovarian tumors: morphological scoring
      system and tumor markers.
AB  - OBJECTIVE: To investigate the importance of morphological scoring systems in
      differentiation of ovarian tumors in childhood. METHODS: Morphological assessment
      using DePriest's index was performed for all patients with histopathological
      confirmation of ovarian tumor, with evaluation of tumor markers, from January
      1997. RESULTS: Fifty-three girls (age range 13 months to 19 years) were
      surgically treated for 59 ovarian tumors, including six bilateral. All lesions
      with cystic appearance on ultrasonography were benign, 23 of 35 semisolid, and
      four of ten solid tumors were also benign. Stage of malignant disease was as
      follows: stage I, ten; stage II, two; stage III, six. Sensitivity, positive
      predictive value and accuracy by DePriest's and Ueland's indexes for benign
      tumors (score <7) were: 0.88, 0.79; 0.89; and 0.94, 0.84; 0.93; respectively.
      Elevated levels of tumor markers were observed in 17 patients, including four
      patients with endocrine manifestations. In 24 patients ovaries were successfully
      preserved, including two patients with foci of immature teratoma in a dermoid
      cyst. CONCLUSION: Ultrasonographic assessment with morphological analysis
      recommended by DePriest and Ueland is a very useful procedure for differentiating
      benign from malignant ovarian tumors in children. Tumor markers and
      endocrinological investigation are also useful for preoperative evaluation.

PMID- 17172085
TI  - A signaling role for leptin in puberty onset in female rats?
AB  - The brain might initiate puberty in response to adequate leptin signaling from
      the periphery. We studied the link between whole body fat, plasma leptin levels,
      and puberty onset, in both controls and food-restricted female Wistar rats from
      age 22 to 42 days. Body fat correlated positively with the prevailing plasma
      leptin levels (r = 0.776) and with the time of puberty onset, i.e. vaginal
      opening (VO) (r = 0.691). Blood samples collected every other day at ZT 2, 6, and
      12, showed a diurnal rhythm in leptin levels with a nadir at ZT 6. Furthermore,
      leptin levels increased over the pubertal period. Food restriction (FR) delayed
      the time of VO considerably (median VO at 38 vs 28 d), and body fat and plasma
      leptin levels were lower in the FR group (p <0.01), although the positive
      correlation between body fat and leptin levels remained. Only the absolute, but
      not the relative amount of body fat increased with age. These data support the
      notion that leptin could indeed serve as the link between nutritional status and
      the reproductive axis, and in this way participate in the timing of puberty.

PMID- 17172086
TI  - Hypercalcemia in a newly arrived international adoptee.

PMID- 17172087
TI  - Prolongation of growth by treatment of 11-hydroxylase deficiency with depot
      leuprolide, growth hormone, and hydrocortisone.
AB  - A 4-10/12 year-old boy presented with tall stature and advanced secondary sexual
      characteristics. His bone age was 13 years giving him a height prediction of 147
      cm. An initial 11-deoxycortisol level of 13,770 ng/dl and associated hypertension
      suggested the diagnosis of 11-hydroxylase deficiency, which was confirmed by
      dexamethasone suppression and genotyping. Treatment strategy was based on the
      premise that known hypothalamic priming resulting in early pubertal development
      could be averted by delaying puberty with leuprolide; also that effects of
      hydrocortisone and leuprolide on attenuating growth could be counteracted by
      growth hormone. The combined treatment resulted in a final height at age 12 years
      which was 25.4 cm greater than predicted, and bone density above average. We
      conclude that delaying puberty until an appropriate age, offsetting growth
      suppression, and improving bone mineralization can be effectively achieved using
      glucocorticoids, leuprolide and growth hormone in patients with 11-hydroxylase
      deficiency.

PMID- 17172088
TI  - Some effect of metformin on insulin resistance in an infant with leprechaunism.
AB  - Leprechaunism was first recognized in 1954 and is characterized by severe
      intrauterine and postnatal growth retardation, failure to thrive, lipoatrophy,
      dysmorphic features (globular eyes, large ears, and micrognathia), hirsutism and
      acanthosis nigricans. The presented infant, a 30 day-old boy, had multiple
      phenotypic anomalies, including low-set ears, prominent eyes, decreased
      subcutaneous fat, hirsutism, breast hyperplasia, and penile enlargement. We found
      persistent hyperglycemia with remarkably high immunoreactive insulin levels. His
      phenotypic and laboratory features were consistent with a diagnosis of
      leprechaunism. We observed some effect of treatment with metformin but not with
      insulin glargine.

PMID- 17172089
TI  - Cushing's disease in a 5-month infant due to a basophilic microadenoma of the
      pituitary gland.
AB  - We report a female patient who developed severe Cushing's disease during the
      fifth month of life due to a basophilic pituitary adenoma Histological findings
      showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis
      of Cushing's disease. The infant died because of untreatable septic shock. The
      importance of the present report resides in the age of the child at diagnosis,
      and that it was the necropsy finding of microadenoma which clarified the cause of
      the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease
      is most often diagnosed in children older than 7 years, and our patient was only
      5 months old when we detected the pituitary adenoma, the earliest case diagnosed
      so far. Cushing's syndrome in pediatric patients has been rarely reported and
      most cases are due to functioning adrenal tumors, usually a malignant carcinoma
      but occasionally a benign adenoma. The present case shows that the pituitary of
      these patients should be investigated with important implications in terms of
      therapeutic approaches, such as pituitary radiotherapy, which can cure the
      patient when treatment is started very soon.

PMID- 17172090
TI  - Donor splice mutation in the 11beta-hydroxylase (CypllB1) gene resulting in sex
      reversal: a case report and review of the literature.
AB  - BACKGROUND: Mutations in the gene encoding 110-hydroxylase (CYPI]BJ) are the
      second most common cause of congenital adrenal hyperplasia (CAH), a disorder
      characterized by adrenal insufficiency and virilization of female external
      genitalia. OBJECTIVE: We describe a new case of 1113-hydroxylase CAH caused by
      donor splice site mutation in the CYPllB1 gene. PATIENT: A 46,XX patient of
      Pakistani descent was identified with severe virilization soon after birth. The
      karyotype was negative for SRY. Pelvic ultrasound showed normal uterus and
      cervix. Periniogram revealed a 3-cm long urogenital sinus, ACTH stimulation test
      showed normal 17-hydroxyprogesterone, low cortisol, elevated 11-deoxycortisol and
      deoxycorticosterone (DOC) levels, consistent with 11beta-hydroxylase deficiency.
      Glucocorticoid treatment was started on the basis of a low baseline cortisol and
      severely virilized external genitalia. The patient did not develop salt wasting
      and/or hypertension. RESULTS: Analysis of the CYPllBlgene revealed homozygosity
      for a codon 318+1G--C substitution at the 5'-splice donor site of intron 5
      resulting in a missense mutation. The parents of the patients are consanguineous
      and are heterozygous for the same mutation. CONCLUSIONS: In a previous reported
      case a donor splice mutation was identified for the first time at the same
      position codon 318 of the CYPIIB1 gene. We present this case in detail along with
      a literature review of 11beta-hydroxylase deficiency CAH.

PMID- 17172091
TI  - Organizational structure and design.

PMID- 17172092
TI  - Ready, set, go... getting ready for 2007.

PMID- 17172093
TI  - Building an outpatient imaging center: A case study at genesis healthcare system,
      part 2.
AB  - In the second of 2 parts, this article will focus on process improvement projects
      utilizing a case study at Genesis HealthCare System located in Zanesville, OH.
      Operational efficiency is a key step in developing a freestanding diagnostic
      imaging center. The process improvement projects began with an Expert Improvement
      Session (EIS) on the scheduling process. An EIS session is a facilitated meeting
      that can last anywhere from 3 hours to 2 days. Its intention is to take a group
      of people involved with the problem or operational process and work to understand
      current failures or breakdowns in the process. Recommendations are jointly
      developed to overcome any current deficiencies, and a work plan is structured to
      create ownership over the changes. A total of 11 EIS sessions occurred over the
      course of this project, covering 5 sections: Scheduling/telephone call process,
      Pre-registration, Verification/pre-certification, MRI throughput, CT throughput.
      Following is a single example of a project focused on the process improvement
      efforts. All of the process improvement projects utilized a quasi methodology of
      "DMAIC" (Define, Measure, Analyze, Improve, and Control).

PMID- 17172094
TI  - CTRM raises the bar for patient safety and staff productivity.
AB  - Ever since the Joint Commission on Accreditation of Healthcare Organizations
      (JCAHO) included medical communications among its National Patient Safety Goals,
      hospital administrators have become increasingly aware of this weak link in
      healthcare delivery. A growing number of hospitals, including Parkland Memorial
      Hospital in Dallas, are implementing critical test result management (CTRM)
      technology that specifically addresses and solves the problem of critical values
      reporting. CTRM technology did not even exist until 2-3 years ago. Now that it is
      here, it will likely become standard practice for hospitals everywhere.

PMID- 17172095
TI  - Due diligence: Conducting a basic compliance audit.

PMID- 17172096
TI  - DRA 2005: The brave new world.
AB  - The Deficit Reduction Act (DRA) of 2005 was signed into law to achieve 39 billion
      dollars in reductions from federal spending programs, 11 billion dollars from
      Medicare and Medicaid alone. Conservative estimates indicate that imaging alone
      accounts for 2.8 billion dollars of that amount. As of the writing of this
      article, both houses of Congress were reviewing bills with bipartisan support
      aimed at defusing, at least temporarily, the negative impact of the DRA; however,
      these bills do not affect the law in totality. Dealing with the changes that the
      DRA will force upon outpatient imaging practices will require all parties
      involved in outpatient imaging--physicians, administrators, and staff alike--to
      make smart, efficient, but practical changes in operational models to effectively
      survive in this new legislatively mandated environment.

PMID- 17172097
TI  - Scorecards.

PMID- 17172098
TI  - Still alive at 55.

PMID- 17172099
TI  - [Strengthen immunization of medical and health care workers against hepatitis B].

PMID- 17172100
TI  - [Effect of nutritional status during infancy and childhood on the risk of
      overweight and obesity in adulthood].
AB  - OBJECTIVE: To examine the association between fetal nutritional status and
      overweight and obesity in their adulthood and to provide evidence for formulation
      of the strategy on preventing low birth weight. METHODS: Using data from 2002
      Nationwide Nutrition and Health Survey to set up a case-control method in order
      to compare body mass index(BMI), prevalence of overweight and obesity as well as
      to calculate odds ratio of overweight and obesity of case group compared with
      control group. Three case groups were selected from those who were born in 1959,
      1960,1961 respectively, and the controls were those who were born in 1964.
      RESULTS: The health consequence of being famines on adulthood was evident in
      women. Means of BMI in women were significantly higher in three case groups than
      that in control group(P<0.01). After adjustment on geographic regions, the
      prevalence of overweight in women was significantly higher in three case groups
      than that in control group(P< 0.01). The prevalence rates of obesity were
      significantly higher in 1959, 1960 groups than 1964 group(P< 0.05). The odds
      ratios of overweight of women in three case groups were 28.9% (95% CI:1.063
      1.565), 37.2% (95% CI:1. 136-1.658) and 35.2% (95% CI: 1. 103-1.657)
      respectively, all higher than that in the control group. The odds ratios of
      obesity of women born in 1959, 1960 groups were 46.5% (95% CI: 1.088-1.972) and
      39.6% (95% CI: 1.039- 1.876) respectively, higher than that in the 1964 group.
      However, such differences were not found in men. CONCLUSION: Higher risks of
      overweight and obesity in women were caused by malnutrition during their fetal
      lives. A strategy on preventing low birth weight should be formulated by the
      government to prevent the chronic disease in adulthood.

PMID- 17172101
TI  - [Study on the effect of malnutrition and anemia identified among general
      population in 2002 to the future productivity in China].
AB  - OBJECTIVE: To measure the social productivity loss and negative effect to
      economic development due to malnutrition in view of quantitative analysis.
      METHODS: Using the data of childhood stunting and population anemia status,
      collected by 2002 National Nutrition and Health Survey to analyse the effect on
      present and future productivity. PROFILES model was used to estimate two kinds of
      productivity losses: "Future productivity loss" was figured out based on the data
      of stunting and anemia status in 0-5 year-old children while "Current
      productivity loss" was from anemia data of the adults. RESULTS: If current
      prevalence levels of malnutrition remained unchange over the next ten years (from
      2002 to 2012), the total net present value of future productivity lost would be
      281.7 billion Yuan (RMB), equivalent to 2.70 % of the Gross Domestice Product(
      GDP) in 2002, with the productivity losses due to stunting, anemia in adults and
      children were 0.15 % , 0.46 % and 2.09% of the 2002 GDP, respectively. All the
      results of calculation mentioned above was restricted with the same assumption -
      the ignorance of the real cost. CONCLUSION: The social economic development and
      the improvement of nutrition program would have a huge effect to population
      nutritional status. The social benefit and return on investment should be
      significant.

PMID- 17172102
TI  - [A cohort study on the relationship between body mass index and blood pressure,
      blood lipid, blood glucose, left ventricular structure and function in
      adolescents during transition period].
AB  - OBJECTIVE: To investigate the relationship between body mass index(BMI) and blood
      pressure, blood lipid level, blood glucose, left ventricular structure and
      function in adolescents during transition period. METHODS: A vertical sectional
      survey on 193 pupils aged 7-11 years in primary school in 1996 was performed. 9
      years later, the same research subjects aged 16-20 years were studied again in
      2005. The subjects were divided into obesity,overweight and normal weight groups
      according to their BMI in 1996. Height, body weight, blood pressure, total
      cholesterol, triglyceride and blood glucose were collected and analyzed, and left
      ventricular structure and function were examined by echocardiography. RESULTS:
      Body mass index (24.71 kg/m(2)+/-4.57 kg/m(2), 20.54 kg/m(2)+/-2.84 kg/m(2) ),
      systolic blood pressure (117.22 mm Hg+/-17.44 mm Hg vs. 102.20 mm Hg+/-11.68 mm
      Hg), thickness of inter-ventricular septum and posterior wall (0.87 cm+/-0.12 cm
      vs. 0.77 cm+/-0.12 cm, and 0.91 cm+/-0.13 cm vs. 0.79 cm+/-0.31 cm), left
      ventricular mass and mass index (167.84 g+/-16.29 g vs. 128.95 g+/-63.00 g, and
      88.12 g/m(2) +/-17.19 g/m(2) vs. 79.35 g/m(2)+/-39.01 g/m(2)) were found
      significantly higher in obesity group than in normal weight group 9 years later
      (P<0.05, P< 0.01 or P< 0.001). End diastolic volume and cardiac output were
      increased(P <0.05) and ejection fraction and fractional shortening decreased( P<
      0.05). There were no differences found in cardiac diastolic function between the
      studied groups. CONCLUSION: The results suggested that simple obesity in
      childhood was an important cardiovascular risk factor when they grew into
      adolescents and adults. ;

PMID- 17172104
TI  - [Investigation on the patterns and knowledge regarding domestic violence among
      married women in rural areas of China].
AB  - OBJECTIVE: To understand the knowledge and prevalence of domestic violence (DV)
      among married women in rural China. METHODS: Proportional to Population Size(PPS)
      sampling method was conducted to select 3998 women aged 18 years old and above
      from Jilin, Anhui and Chongqing. All the women were interviewed using a
      standardized questionnaire during Nov. 2004-Jan. 2005. RESULTS: The prevalence of
      spousal violence against women was 64.8 % in a lifetime and 42.6% in the past 12
      months before the survey. Psychological violence was the most common type,
      followed by physical violence and sexual abuse. The prevalence rates for
      psychological, physical and sexual violence in a life time were 58.1%, 29.7%,
      16.7%, while 37.2%, 14.0%, 7.7% in the past 12 months before the survey. All the
      total DV, psychological violence and sexual violence were more commonly seen in
      Jilin province, while physical violence was more prevalent in Chongqing city. The
      prevalence rate of violence was different among people with different social
      demographic characteristics. Sexual abuse became more common with the improvement
      of education. In total, about 1/3 women suffered two or three categories of
      violence at the same time. Most sexually abused women suffered one kind of
      violence, while half of the physically and psychologically abused women suffering
      two and more kinds of violent behaviors at the same time. Married women had
      relatively little knowledge on domestic violence and 75.2 % of the women did not
      even know what domestic violence was referring to and some women suffered from DV
      themselves but knowing nothing about its implication. In general, physical
      violence was better understood among interviewed women while the knowledge about
      psychological violence was relatively poor. Conclusion Domestic violence,
      psychological violence in particular, was very common in rural China, while the
      knowledge of DV among married women was poor, effective actions should be taken
      to stop DV at no time.

PMID- 17172103
TI  - [Plasma and red blood cell folate levels among women in their first trimester of
      pregnancy from rural areas with high or low prevalence of neural tube defects,
      China].
AB  - OBJECTIVE: To compare plasma and red blood cell folate levels among women in
      their first trimester of pregnancy from rural areas with high or low prevalence
      of neural tube defects. METHODS: A cross-sectional study was performed, among
      women in their first trimester of pregnancy from rural areas with high or low
      prevalence of neural tube defects in 2003. Non-fasting blood sample were
      collected and analyzed for plasma and red blood cell folate concentrations for
      688 women. RESULTS: The median plasma (10.53 nmol/L) and red blood cell folate
      (389.2 nmol/L) among women from the high prevalence rural area were lower than
      those of women from the low prevalence rural area (plasma folate: 30.39 nmol/L,
      red blood cell level folate: 926.0 nmol/L). Among women from the high prevalence
      area, about 50% and 43% were respectively, deficient for plasma and red blood
      cell folate, compared with 6% and 4% respectively, for women from the low
      prevalence area. The median plasma folate levels among women who took
      periconceptional folic acid supplements in both high and low prevalence areas
      were about twice higher than those who did not take the folic acid. The median
      red blood cell folate level of the folic acid users was 40% higher than those of
      the non-users. Among those who took folic acid, women in the low prevalence area
      had 70%-90% higher plasma folate concentration and twice higher red cell folate
      concentration than women in the high prevalence area. CONCLUSION: Women from the
      rural area with a high prevalence of neural tube defects had low plasma and red
      blood cell folate levels. Periconceptional supplementation with folic acid could
      substantially improve folate status of reproductive-aged women. However,
      supplementation with 0.4 mg of folic acid per day might be inadequate for women
      in the high prevalence rural area.

PMID- 17172105
TI  - [Study on the risk factors of repeated abortion among unmarried adolescents].
AB  - OBJECTIVE: To find out the rate of repeated induced abortion among unmarried
      abortion women and to study the relevant risk factors. METHODS: From July to
      September 2005, we used the method of hospital based descriptive epidemiological
      study to investigate 2295 abortion women below 25 years of age in Beijing,
      Shanghai and Zhengzhou. Case-control study was used as the method. We considered
      the women with history of repeated abortion as case group (736 women) and
      considered the women without history of repeated abortion as control group (1559
      women). RESULTS: The mean age of respondents was 21.92 years with minimal age as
      15 years. 17.2 % aborted women aged below 20 years with 32. 1% of them were ever
      having a history of previous induced abortion. Among 736 women with repeated
      abortion, 75.3 % of them had one time of induced abortion previously, 18.1%
      having two times, 4.2% having 3 times, 13 women having 4 times and 4 women having
      5 times and one even with the maximum of having 8 times of previous abortion. In
      comparison with control group, the case group had higher rate among women whose
      first sex was below 18 years (16.2% vs. 9.4% , P<0.01). There were higher rates
      of women under following conditions: having exposed to sexual behavior for more
      than 3 years (33.6% vs. 6.6 % , P<0.01), having cohabited with male partner for
      over 1 year (64.6% vs. 23.9%, P <0.01), having regular sexual life (48.5 % vs.
      37. 1%, P < 0.05), having multiple sexual partners (36.0% vs. 15.0%,P<0.01)
      having unwanted sex (6.0% vs. 3.9%, P<0.05), whose current pregnancy resulted
      from contraceptive failure (39.3% vs. 31.6%, P< 0.01), having a history of high
      risk abortion (30.8% vs. 3.1%, P< 0.01) etc. In comparison with the control
      group, the case group showed higher rates of male partners not supporting this
      induced abortion, male partner not participating in decision-making on abortion
      and male partner not accompanying the female partners to seek for abortion
      service (rates of the three major factors in case group and in control group were
      10.3% vs. 5.9%, P< 0.01, 30.3% vs. 24.0%, and 27.5% vs. 23.5%, P<0.01,
      respectively). CONCLUSION: The rate of repeated induced abortion among unmarried
      abortion women was relatively high. The risk factors for females would include:
      younger age of sex debut, longer duration from the beginning of first sex to the
      current abortion, cohabitation, regular sexual life, multiple sexual partners,
      unwanted sex, contraceptive failure and high risk induced abortion. Meanwhile,
      unmarried but repeated abortion was related to the differences of gender between
      males and females and male partner's concern on induced abortion.

PMID- 17172106
TI  - [Astrovirus infection among hospitalized children with acute diarrhea in seven
      regions of China, 1998-2005].
AB  - OBJECTIVE: To study the epidemiology and strain variations of astrovirus
      infection among children under 5 years of age, hospitalized for acute diarrhea in
      China. METHODS: Inpatients under 5 years of age with acute diarrhea in hospitals
      of seven provinces between 1998 and 2005 were enrolled in the study Stool
      specimens were collected and tested for astrovirus using the Dako Amplified IDEIA
      Astrovirus kits or reverse-transcription polymerase chain reaction (RT-PCR).
      Genetic identities of the strains were determined using RT-PCR with serotype
      specific primers and confirmed by sequencing of the RT-PCR products. RESULTS: A
      total of 1668 diarrheal stool samples tested for both rotavirus and calicivirus
      negative were examined. The detection rate of astrovirus infection was 5.5%
      (91/1668) and the diarrhea cases caused by astrovirus infection could be found in
      any season of the year but mainly occurred in cold season from October to next
      January. Astrovirus detection-rates were: 7.4% among infants aged 9-11 months
      followed by 6.1% in 12-17 month-olds, and 6-8 months 5.6% & 0-2 months 5.6%
      before 8 months. Over 95% of astrovirus infections occurred in children before 2
      years of age. Among 49 strains, typed, serotype 1(45/91) was most commonly seen
      while serotype 5 was in two cases and serotype 3 and 8 were detected in only one
      case respectively. CONCLUSION: Astrovirus seemed an important etiologic agent in
      young children with acute diarrhea in China and Serotype 1 was the most prevalent
      one.

PMID- 17172107
TI  - [Molecular typing of the pathogenic Yersinia enterocolitica strains with pulsed
      field gel electrophores isolated in China].
AB  - OBJECTIVE: To investigate the epidemiological and molecular typing features of
      the pathogenic Yersinia enterocolitica strains isolated in China,using pulsed
      field gel electrophoresis(PFGE) and standardized PFGE method as well as typing
      database of Yersinia enterocolitica. METHODS: PFGE analysis was performed as
      Laboratory Directions for molecular subtyping of Salmonella by PFGE
      (PulseNet,USA) with some modifications and the results of PFGE were analyzed by
      BioNumerics soft (Version 4.0, Applied Maths BVBA, Belium). RESULTS: 114 O:3
      Yersinia enterocolitica strains were typed by 25 patterns to have found that
      K6GN11C30012 (50 strains), K6GN11C30015(19 strains) and K6GN11C30016(10 strains)
      were the major patterns. K6GNllC30012 had 92.2% cluster similarity with
      K6GN11C30009-K6GN11C30023. This clone included 91.23% strains of 114 0:3 Yersinia
      enterocolitica strains. 51 0:9 Yersinia enterocolitica strains were typed by 14
      patterns; K6GN11C90004 (22 strains) and K6GN11C90010 (13 strains)were the major
      patterns. K6GN11C90004 had 81.8% cluster similarity with K6GN11C90010 patterns.
      The major patterns of 0:3 and 0:9 serotypes were quite different. CONCLUSION: O:3
      Yersinia enterocolitica strains might originate from the same clone and had very
      few variation in different years and provinces but O:9 Yersinia enterocolitica
      strains from two different clones with some changes.

PMID- 17172108
TI  - [Investigation on Borrelia burgdorferi sensu lato in ticks and rodents collected
      in Da Xing-An Mountains Forest areas of China].
AB  - OBJECTIVE: To detect and study the types of Borrelia burgdorferi sensu lato in
      ticks and rodents from Da Xing-An Mountains Forest areas of China. METHODS:
      Nested PCR was performed to amplify 5S-23S rRNA intergenic spacer of B.
      burgdorferi. Positive products were analysed by restriction fragment length
      polymorphism (RFLP) and single strand conformation polymorphism (SSCP), specimens
      showing unique RFLP profile were sequenced and analysed. RESULTS: 1336 Ixodes
      persulcatus, 144 Dermacento silvarum, 144 Haemaphysalis concinna and 145 rodents
      of 9 species were collected from 16 sections of Da Xing-An Mountains Forest areas
      of China. Specific fragments were amplified from 293 I. persulcatus and 6 D.
      silvarum and 5 rodents of 4 species. B. burgdorferi was not detected in H.
      concinna. Among the positively tested I. persulcatus, 209 contained B. garinii
      genospecies and 45 contained B.afzelii genospecies based on RFLP. Moreover,
      B.garinii genospecies consisted of B. garinii 20047 and B. garinii NT29. 17 adult
      I. persulcatus were simultaneously infected with B. garinii 20047 and B. garinii
      NT29. Nine adult I. persulcatus were simultaneously infected with B. garinii
      20047 and B. afzelii. Four adult I. persulcatus were simultaneously infected with
      B. garinii 20047 and B. garinii NT29 and B. afzelii. Two D. silvarum were
      infected with B. garinii 20047, 1 D. silvarum with B. garinii 20047, 2 D.
      silvarum with B. afzelii. 3 rodents were infected with B. garinii 20047 while 2
      rodents were infected with B. garinii NT29. Mixed infection was not found in D.
      silvarum and rodents. In addition, nine I. persulcatus and one D. silvarum
      specimens showed unique RFLP pattern. Data from sequential analysis showed that
      they all belonged to B. garinii. PCR-SSCP profiles of 5S-23S rRNA intergenic
      spacer of B. burgdorferi in the positive specimens exceeded 36 types; B. garinii
      20047 showed 16 types while B. garinii NT29 showing 11 types, B. afzelii showing
      9 types. SSCP profiles of the specimens coinfected with multiple B. burgdorferi
      was relatively complex. CONCLUSION: The infection of B. burgdorferi was found in
      the ticks and rodents in Da Xing-An Mountains Forests areas. The infection rate
      of I. persulcatus was high. B. garinii was predominant genospecies, and the
      population of B. burgdorferi was heterogeneous in the area. Mixed infections of
      different B. burgdorferi genospecies in ticks were found. I. persulcatus and
      Clethrionomys rufocanus were possibly served as major vector and major host for
      B. burgdorferi, respectively, suggesting that further study is needed to confirm
      the coinfection in humans and animals in this region.

PMID- 17172109
TI  - [Observation on two kinds of recombinant hepatitis B vaccines used in populations
      with different immunity].
AB  - OBJECTIVE: To evaluate the immunity status on different hepatitis B vaccines
      currently being used in Beijing. METHODS: College students who had not received
      hepatitis B vaccine and children who had received whole-course immunization at
      birth, were tested HBsAg, anti-HBs and anti-HBc. All the test-negative cases were
      served as research subjects. 3 doses recombinant hepatitis B vaccines were given
      to the college students, following the 0, 1, 6 months schedule. Among which, 140
      cases received recombinant beer yeast hepatitis B vaccine (BY vaccine, 10 microg,
      5 microg, 5 microg), and 140 cases with recombinant hansenula polymorpha
      hepatitis B vaccine (HP vaccine, 10 microg, 10 microg, 10 microg). 1 dose was
      given for boosting immunization to 98 children, in which 49 cases with BY vaccine
      (5 microg) and 49 cases with HP vaccine (10 microg). Anti-HBs was tested 1 month
      after. RESULTS: The total positive (> or = 10 mIU/ ml) rate was lower among BY
      vaccine group than HP vaccine group for the college students (93.5 %, 99.3% ,
      P<0.05), but no statistical difference on GMT(81.2 mIU/ml, 94.6 mIU/ml, P>0.05)
      was found. For males, the positive rate and GMT were lower in BY vaccine group
      than in HP vaccine group (85.7% ,100.0%, P<0.01)(56.6 mIU/ml, 98.6 mIU/ml,
      P<0.01), but with no statistical difference for females (98.8%, 98.5%, P> 0.05)
      (103.4 mIU/ml, 90.3 mlU/ml, P> 0.05). For the same vaccine, the positive rate and
      GMT were lower in males than in females when using BY vaccine (85.7% , 98.8%,
      P<0.01)(56.6 mIU/ml,103.4 mIU/ml, P< 0.01), but no statistical difference was
      found on HP vaccine(100.0%, 98.5%, P>0.05)(98.6 mIU/ml, 90.3 mIU/ml, P>0.05). The
      positive rate of anti-HBs was decreasing along with age among the children who
      had received a whole-course immunization at birth (P <0.01). 98.6 % of the 70
      negative cases appeared positive conversion after receiving 1 dose and the GMT
      raised significantly by 15 times. No statistical difference was found between the
      two kinds of vaccines(100.0%, 97.4%, P>0.05)(80.5 mIU/ml, 68.5 mIU/ml, P>0.05).
      CONCLUSIONS: The type of vaccine and sex were related to the effects, better with
      HP vaccine than BY vaccine in males but was the same for females in adults
      receiving basic immunization according to the conventional doses. Both kinds of
      vaccines were ideal when children receiving boosting immunization. The immune
      memory was good for persons who had received primary immunization with
      recombinant vaccine but antibody appeared negative conversion. It was not
      necessary to boost immunization within 6 years after a whole-course immunization
      with recombinant hepatitis B vaccine in infancy.

PMID- 17172110
TI  - [Surveys on the implementation of "rules on stop smoking in the public places in
      Beijing" from 1997 to 2004].
AB  - OBJECTIVE: To find out the situation of the implementation on "rules on stop
      smoking in the public places in Beijing", a study was carried out to compare the
      results from 1997 and 2001. METHODS: Thousands of residents aged above 15 in a
      family were sampled by stratified sampling, and 4 districts were selected as
      study locales. RESULTS: (1) About 40% of the department or school leaders
      considered much about the work on banning of smoking with 70 % of the departments
      or schools having posters of signs on 'ban on smoking' in the meeting rooms. (2)
      Some of the departments or schools had inspectors looking after the issue. (3)
      60% of the people had never or 10% had seen that the inspectors ever criticizing
      or punishing the smokers who violating the rules. (4) People still often saw some
      one would smoke in public (the rates were 19.53% , 37.89% , 6.35% respectively in
      1997,2001,2004 ). (5) People received the information of these rules through TV
      news or newspaper. CONCLUSION: Although success had been achieved since the
      implementation of the Rules, it did not seem to have had substantial progress.

PMID- 17172111
TI  - [Roadside observation on the use of safety belt in Guangzhou and Nanning cites of
      China].
AB  - OBJECTIVE: To determine the rates of correct use of safety belt (CUSB) among
      drivers and front seat passengers in Guangzhou and Nanning through roadside
      observation and to provide scientific evidence for the development of
      intervention plan and to strengthen road safety law enforcement. METHODS:
      Observational sites were randomly selected from three road types (Highway, Main
      Street and Subordinate Street). Targeted automobiles were observed at each site
      at four different times and uniformed checklists were used to record safety belt
      use during observations. Within each vehicle, belt use by drivers of different
      sex, road type, workday/weekend, day/night and seating position were calculated.
      Data was analyzed, using Chi-square tests to compare the statistic significance.
      RESULTS: (1)The rate of CUSB and non-use rate among drivers were higher in
      Nanning than in Guangzhou (P= 0.00) but the rate of incorrect use was on the
      contrarary. (2) The rate of CUSB by front seat passengers in Guangzhou was higher
      than that in Nanning (P = 0.04); as well as the rate of (P = 0.00) incorrect use
      while the non-use rate was on the contrarary. (3)In general, the rate of CUSB was
      higher on highways than on local streets (P = 0.00). (4) The CUSB rate of drivers
      and front seat passengers was higher at daytime than at night (P = 0.00), and the
      rate of incorrect use was higher at working days than weekends (P = 0.00). (5)
      The CUSB rate was higher for female drivers than for males in Guangzhou (P =
      0.00), but there no statistical significance was found in Nanning (P = 0.21).
      CONCLUSION: Results suggested that intervention actions should be undertaken to
      raise the awareness of the importance of safety belt use. Effective public
      information and education programs, law enforcement and mandatory safety belt
      use, prioritizing programs on people neglegent to the importance are necessary to
      increase the safety belt use and to decrease the mortality and injuries caused by
      traffic accidents.

PMID- 17172112
TI  - [Study on fluoroquinolone resistance and the relationship between resistance and
      mutations of gyrA and parC in Neisseria gonorrhoeae].
AB  - OBJECTIVE: To study the phenotypic and genotypic resistance to Fluoroquinolones
      in Neisseria gonorrhoeae (NG) isolated in Jiangsu province of China. METHODS: In
      vitro, susceptibility testing of ciprofloxacin and levofloxacin against ninety
      five clinical isolates were determined by agar dilution method. Detection of
      mutation in the gyrA and parC genes was performed by polymerase chain reaction
      (PCR) assay and sequence analysis. RESULTS: The clinical isolates demonstrated
      100% resistance to ciprofloxacin. Based on gyrA and parC mutations, 18 types
      could be categorized among the 54 isolates. Based on the same gyrA
      mutations,isolates with high MIC appeared to have had more mutations in parC
      gene. CONCLUSION: The status of resistance to ciprofloxacin in NG was quite
      serious, and ciprofloxacin treatment for the treatment of NG infections in
      Jiangsu province should not be recommended. The results from this study suggested
      that mutations in the parC gene had contributed to the development of high
      Fluoroquinolone resistance in NG.

PMID- 17172113
TI  - [Study on the genotyping of 113 Mycobacterium tuberculosis strains isolated in
      Beijing based on 13 variable number of tandem DNA repeats].
AB  - OBJECTIVE: Variable Number of Tandem Repeats (VNTRs) analysis was a recently
      developed method which could serve as a 'real-time' genotyping tool for
      Mycobacterium tuberculosis. One hundred and thirteen M. tuberculosis isolates
      from the patients with tuberculosis in Beijing were analysed using the reference
      method to study the characters of genetic diversity and genotype. METHODS:
      Thirteen tandem repeat loci (ETR-A, ETR-C, ETR-D, MIRU10, MIRU16, MIRU27, MIRU31,
      MIRU40, Mtub21, Mtub30, Mtub38, Qublla, Qubllb) in the total genome of MTB were
      analyzed by PCR and agarose gel electrophoresis method. The characters of the
      polymorphism of DNA fingerprinting of one hundred and thirteen MTB strains were
      analyzed with Gel-Pro analyzer 3.1 software and BioNumerics 3.0 software. Results
      One hundred and thirteen MTB strains were characterized and classified in to four
      genotype families(type I , type II , type NV, type V ) based on thirteen tandem
      repeat loci. One hundred and four isolates(92.0%) belonged to type I , the other
      three genotypes scattered, five strains(4.4%) remaining with type II , while type
      IV and type V having the same quantity 1.8% (2/113). M. tuberculosis H37Rv
      belonged to a unattached genotype(type ll ). Conclusion There was obvious length
      polymorphism in the M. tuberculosis isolates which implied that type I was the
      epidemic strain clusters in M. tuberculosis in Beijing. VNTRs analysis seemed to
      be a simple, rapid, sensitive and valuable tool for epidemiological studies of M.
      tuberculosis complex organisms.

PMID- 17172114
TI  - [Study on the correlation among quantification of HBV-DNA and HBeAg, anti-HBe in
      hepatitis B carriers].
AB  - OBJECTIVE: To better understand the duplication of hepatitis B virus (HBV) in
      order to improve clinical diagnoses and treatments via quantitative measurement
      of HBV-DNA and comparison of correlation of HBV-DNA with HBeAg and anti-HBe.
      METHODS: For 883 hepatitis B patients with positive HBsAg, HBV-DNA was measured
      by COBAS AMPLICOR HBV MONITOR reagent and COBAS AMPLICOR quantitative PCR
      instrument. Microparticle enzyme immunoassay analysis (MEIA) was then carried out
      with fully automatic enzyme immunoassay analysis instrument made by Abbott Axsym
      from the U.S. to measure HBeAg and anti-HBe. Correlation was analysed by SPSS.
      RESULTS: (1)Positive correlation between 690 HBV-DNA positive and HBeAg positive
      with r= 0. 505 (P< 0.01) was found with mean values as:HBV-DNA:7.12 x 10(12)
      copies/ml;HBeAg:218.31 S/CO. HBV-DNA:10(4) copies/ml, HBeAg: 104 S/CO; HBV-DNA:
      10(5)-10(8) copies/ml, HBeAg: 112 S/CO; HBV-DNA: 10(9)-10(15) copies/ml, HBeAg:
      252 S/CO. (2) No correlation was found between 193 HBV-DNA and anti-HBe + with r=
      -0.052(P= 0.477> 0.05) with Mean: HBV-DNA: 8.0x 10(10) copies/ml anti-HBe: 0.18
      S/CO. CONCLUSION: HBV-DNA and HBeAg appeared to have had linear correlation,
      showing that HBeAg> 100 S/CO,HBV-DNA> 10(4) copies/ml and hepatitis B virus were
      reproduced. However, HBV-DNA did not show linear correlation with anti-HBe as
      HBeAg negative and anti-HBe positive, the level of hepatitis B viral replication
      decrease slightly. But the virus load is still high. Infectivity can not neglect.

PMID- 17172115
TI  - [Use of variable-number tandem repeats to examine genetic diversity of Bacillus
      anthracis].
AB  - OBJECTIVE: To study the genotyping of Bacillus anthracis based on multiple-locus
      variable-number tandem repeats(VNTR) in the B. anthracis genome. METHODS: We
      selected 13 VNTR loci (which cited from published articles) to study 88 strains
      of B. anthracis isolated from China. The methods used were: (1) Selecting the
      primers which were at both ends of the tandem repeat locus; (2) Amplifying the
      sequence of the locus by PCR; (3)cDetecting the PCR products by agarose gel and
      polyacrylamide electrophoresis; (4)Analyzing the PCR products and computing the
      molecular weight by analysis software of gel images;(5) Double-checking with
      sequencing results; (6)Reckoning the repeat numbers and study the VNTRs loci
      characters. RESULTS: (1) We used multiple-locus variable-number tandem repeat
      analysis (MLVA) to characterize 88 B. anthracis isolates from diverse geographic
      locations which were divided into 45 MLVA genotypes and 3 groups through cluster
      analysis. The genotypes was relative to restricted geographical region. It seemed
      clear that the multiple isolates from the same anthrax outbreak frequently having
      identical genotypes. (2)Results from VNTR analysis showed that A16R vaccine
      strain isolated from China was having the nature of representativeness in the
      country. CONCLUSION: Analysis showed that the VNTR patterns was an appropriate
      study method for B. anthracis genetic diversity from different geographical areas
      and different time. Isolates from the same anthrax outbreak had identical

PMID- 17172117
TI  - [The analysis of plasma homocysteine among 1020 residents in community].
AB  - OBJECTIVE: To study the plasma homocysteine (Hcy) distributive characteristics in
      different sex and age groups of the community residents in Guangdong, and to
      analyze its associated factors as well as its effects on cerebral artery
      stenosis. METHODS: In this study, we presented data concerning 2500 residents who
      had undergone a systematic health checkup,including clinical and biologic
      examinations. Plasma was saved from 1020 residents who were asymptomatic but
      having TCD examination. Hcy concentration was measured by fluorescence ration
      biochemical assay kit. RESULTS: The average plasma Hcy levels of males (15.0
      micromol/L+/-5.8 micromol/L) were significantly higher than those of females
      (12.4 micromol/L-I 3.9 micromol/L, P< 0.05). Hcy level increased parallel with
      age. The prevalence rate of hyperhomocysteinemia in males (47.2%) was higher than
      in females (23.2%). Hcy levels in MCA stenosis group (18.3 micromol/L+ 5.3
      micromol/L) were significantly higher than that in control group (12.9
      micromol/L+/- 4.6 micromol/L, P< 0.05). Based on logistic regression analysis,
      Hcy was only associated with sex and age, but not with blood lipids etc.
      CONCLUSION: Hcy levels were different in sex and age groups which emerged as
      independent predictors of hyperhomocysteinemia but had no association with blood
      lipids in the community residents, suggesting that hyperhomocysteinemia might
      worsen cerebral artery stenosis.

PMID- 17172116
TI  - [Study on the results of treating tuberculosis inpatient in the general
      hospitals: a correspondence analysis].
AB  - OBJECTIVE: To understand the current status of treatment among inpatients of
      tuberculosis (TB) in general hospitals, and to related to different attrributes.
      METHODS: A retrospective study was designed for inpatients with TB who were
      discharged from general hospitals in Nachong region, 2003. Factors associated
      with the results of treatment were selected, using Chi-square test. Further
      correspondence analysis (CA) was used to visualize the relationship between
      attributes of inpatients and results of treatment in general hospitals. RESULTS:
      Statistically significant factors associated with treatment results would include
      gender, age, state of illness at access to hospital, comorbidity and length of
      stay, while ways of payment, occupation and marital status were not statistically
      significant. The joint plot of CA showed results as follows: (1) Attributes of
      inpatients died in general hospitals were clearly different from that of cured or
      improved inpatients. (2) Result of hospitalization on treatment was more likely
      to be 'improved' for TB inpatients who were male, aged > or = 15 yrs, and with
      urgent condition when administered into the hospitals. (3) Result of cure was
      likely to be seen among inpatients who were female, length of stay >8 days, with
      no comorbidity, and with average illness state when accessing to hospitals. (4)
      Bad treatment results were appeared for inpatients younger than 15 yrs, with
      critical state when administered to hospitals. CONCLUSION: (1)CA provided us with
      a new way on how to extract useful information from miscellaneous data of the
      patients. (2) The relationships between the results of treatment from the general
      hospitals and TB inpatients' attributes might provide tips to develop a series of
      corresponding strategies for treating TB inpatients with special attributes in
      order to obtain higher cure rate.

PMID- 17172119
TI  - [Increasingly improving outcomes of allogeneic hematopoietic cell
      transplantation].

PMID- 17172118
TI  - [Number needed to be screened in a study: a novel measure for disease screening
      effect].
AB  - OBJECTIVE: To introduce the concept, methods for calculation and application of
      "number needed to be screened" (NNBS) in epidemiologic studies. METHODS: The
      concept of "number needed to treat" (NNT) was extended for disease screening
      strategies. For the purpose of illustration, the values of number needed to
      invite for screening (NNI) and number needed to be screened (NNBS) were
      calculated on the basis of the results from two randomized controlled screening
      trials--Nottingham randomized controlled trial of faecal-occult-blood screening
      for colorectal cancer and Swedish mammographic screening trial for breast cancer
      in two counties. RESULTS: In order to prevent one death from the colorectal
      cancer among local people aged from 45 to 74 during the 14 years of follow-up,
      the NNI and NNBS for faecal-occult-blood screening program were 1220 and 665,
      respectively. In addition, in order to prevent one death from breast cancer among
      local women aged 40-74 during 8 years of follow-up, the NNI and NNBS for
      mammographic screening program were 1961 and 1494, respectively. CONCLUSION:
      Compared with the traditional indices, NNBS can evaluate the overall
      effectiveness of a screening program in an intuitively understandable manner so
      as to facilitate the communication among medical researchers, health workers,
      health policy makers and the public.

PMID- 17172120
TI  - [Correlation between human herpesvirus 6 activation and acute graft-versus-host
      disease after allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To study the potential relationship between HHV-6 activation and acute
      graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell
      transplantation (HSCT). METHODS: Peripheral blood samples were collected before
      and weekly after HSCT from 72 consecutive recipients. HHV-6 DNAemia was monitored
      by nested polymerase chain reaction (PCR). The genotypes of HHV-6 were identified
      by Hind III restriction assay. RESULTS: Of the 72 patients, HHV-6 DNAemia were
      detected in 45 (62.5%) on a median of day 14 (range, 7 - 63 days) after HSCT.
      Grade I - IV aGHVD occurred in 40 (55.6%) on a median of day 26 (range, 9 -73
      days). The median onset time of HHV-6 DNAemia was significantly earlier than that
      of aGHVD (P = 0.018). Compared with that in HHV-6 DNAemia negative [HHV-6(-)]
      patients, the cumulative incidence of grade I - IV aGHVD was higher (68.9% vs.
      33.3% , P = 0.003) in HHV-6 (+) patients. Cumulative incidence of grade II - IV
      aGVHD in HHV-6 (+) cohort was also higher than that in HHV-6 (-) cohort (35.6% vs
      14.8% , P = 0.027). Cumulative incidence of grade I - IV aGVHD was higher in
      patients with both HHV-6 and CMV positive (CMV+/HHV-6+) than in those with either
      CMV (CMV+/HHV-6-) or HHV-6 positive (CMV+/HHV-6+) and neither of them positive
      (CMV-/HHV-6-) [78.9% (30/38), 55. 6% (5/9) , 14. 3% (1/7) and 22. 2% (4/18),
      respectively, P = 0. 0001]. Cumulative incidence of grade II - IV aGVHD in
      CMV+/HHV-6+ group was also higher than that in CMV+/HHV-6-, CMV-/HHV-6+ and CMV
      /HHV-6- groups [42.1% (16/38), 22.2% (2/9), 0% (0/7) and 11.1% (2/18), P = 0.
      008]. CONCLUSIONS: Patients with HHV-6 activation or HHV-6/CMV co-infection maybe
      involved in the occurrence of aGVHD after HSCT.

PMID- 17172122
TI  - [Prophylactic effect of matrix metalloproteinase inhibitor on acute graft-versus
      host disease in a murine model].
AB  - OBJECTIVE: To explore the prophylactic effect of tissue inhibitor of matrix
      metalloproteinase (TIMP) on acute graft-versus-host disease (aGVHD) after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a murine model.
      METHODS: The murine model of aGVHD after allo-HSCT was established by using
      female C57BL/b (H-2b) mouse as the donor, and male BALB/c (H-2b) as the
      recipient. After allo-HSCT, recipient mice were divided into 3 groups. For aGVHD
      prophylaxis group A was given TIMP (2 mg/d) , group B CsA (5 mg x kg(-1) x d (
      1)) was given, and group C nothing. Physical signs, mean survival time (MST),
      peripheral blood counts and aGVHD histopathology were observed. RESULTS: Mice in
      group C developed typical aGVHD and 100% of mortality, with a MST of 8 days, and
      those in group A and B had longer survival, the MST being (4.8 +/- 1.4) d and
      (4.3 +/- 0.9) d respectively, with no statistical difference in peripheral blood
      count between these two groups. Mice in group A showed less severe signs.
      CONCLUSIONS: TIMP markedly prolongs MST of allo-HSCT recipients, delays the onset
      of aGVHD signs, and has no adverse effect on hematopoiesis reconstitution.

PMID- 17172121
TI  - [Monitoring bcr-abl mRNA levels by real-time quantitative RT-PCR in chronic
      myeloid leukemia patients after hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To evaluate the value of real time quantitative RT-PCR (Q-PCR) for
      monitoring bcr-abl mRNA levels in chronic myeloid leukemia (CML) patients after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS:
      Quantification of bcr-abl mRNA was performed on 316 bone marrow samples from 112
      patients with CML after HSCT by Q-PCR using the TaqMan probe system. The bcr-abl
      mRNA level was normalized by control gene abl. Cytogenetic response was evaluated
      with fluorescent in-situ hybridization (FISH). RESULTS: The reproducible
      sensitivity of Q-PCR was 5 copies. The coefficients C(T) of interassay and
      intraassay variation for abl and bcr-abl were all below 2.0%. 289 bone marrow
      samples were collected from 101 CML patients who achieved a sustained complete
      cytogenetic response (CCyR) one month post allo-HSCT in a period of 6 - 60 months
      (median 12 months) at different intervals. In general, the median bcr-abl levels
      gradually decreased with the prolongation of time after HSCT: the median bcr-abl
      levels were 0.035% (0 - 0.406%) at 1 month post allo-HSCT (+ 1 month), 0.006% (0 
      0.683%) at +3 month, 0% (0 - 0.225%) at +6 month and remained 0% till +24
      months. The highest level in CCyR patients detected at + 6 month was 0.068%. The
      bcr-abl mRNA level was decreased by 3 log in sustained CCyR patients at + 1 month
      compared with the newly diagnosed CML-CP patients (33.0%, data unpublished). On
      the contrary, Q-PCR results ranged from 0.12% to 13.45% in 8 cytogenetic non
      responders or relapsed patients post allo-HSCT. Among them, 5 patients' samples
      were collected 1 - 2 months before cytogenetic relapse, the results were ranged
      from 0.09% to 3.42%. If 0.09% was assumed 0.09% as a threshold, 9 sustained CCyR
      patients (8.9%) were tested once higher than that within 6 month after HSCT but
      decreased to 0% eventually. 2 blast crisis patients achieved CCyR within 1.6 and
      3 months after HSCT, but hematological relapse occurred after 1 and 1.5 months,
      and their bcr-abl mRNA levels increased dramatically from 0% and 0.14% to 46.9%
      and 75.9% respectively. CONCLUSIONS: Q- PCR is a sensitive, precise and reliable
      technique, and can be used to monitor CML patients post allo-HSCT regularly.
      Patients in blast phase of CML should be monitored more frequently.

PMID- 17172123
TI  - [Allogenic stem cell transplantation from genotypically HLA-identical siblings
      for 30 patients with myelodysplastic syndromes].
AB  - OBJECTIVE: To explore the indication and optimum time for treating
      myelodysplastic syndrome (MDS) by allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) with HLA identical sibling grafts. METHODS: From June
      1997 to Sep. 2004, a total of 30 patients with MDS were treated with allo-HSCT
      from HLA-identical sibling donors in our institute. On HSCT, 4 patients had
      refractory anemia (RA) , 2 RA with ringed sideroblasts (RARS) , 7 RA with excess
      blasts(RAEB) , 14 RAEB in transformation (RAEB-t) , 3 already progressed to
      secondary AML. For IPSS system, 6 patients were in intermediate- I risk group, 11
      in intermediate- li risk group, and 13 in high risk group. The modified BU/CY
      conditioning regimen was used. Four patients received bone marrow transplantation
      (BMT), 8 received peripheral blood stem cell transplantation (PBSCT) , and 18
      received BMT + PBSCT. RESULTS: The 3-year expected overall survival (OS) was
      63.61%, 3-year expected disease-free survival ( DFS) 61.41%, and relapse rate
      5.26%; OS for RA/ RAS, RAEB and RAEB-t/AML subgroup was 83.33%, 34.29% and 66.67%
      , respectively, and all had no statistic difference among them. OS for IPSS
      intermediate and high risk subgroup was 64.7% , and 69.0% respectively, also had
      no statistic difference. 3-year expected OS in no aGVHD,grade I - II aGVHD and
      grade III - IV aGVHD group was 57.75% , 100% and 0% , respectively (P = 0.009).
      Pre-HSCT chemotherapy, disease subtype and cGVHD all had no correlation with LFS
      or OS (P > 0.05). CONCLUSION: For young MDS patients having HLA-identical sibling
      donors, HSCT should be the first line therapy and performed as soon as possible.

PMID- 17172124
TI  - [Effectiveness of allogeneic peripheral blood stem cell transplantation in 23
      patients with myelodysplastic syndromes].
AB  - OBJECTIVE: To analyse the outcome of allogeneic peripheral blood stem cell
      transplantation (allo-PBSCT) for myelodysplastic syndromes (MDS). METHODS: Twenty
      three patients with MDS received G-CSF mobilized HLA-identical sibling allo
      PBSCT. The numbers of mononuclear cells (MNC) and CD34+ cells were 8. 25 (4.50 
      22.36) x 10(8)/kg and 5.59 (1.57 - 12.22) x 10(6)/kg respectively. CsA and
      shorten course MTX were used for graft-versus-host disease (GVHD) prophylaxis and
      MMF was given on + 1 d - +28 d posttransplantation. RESULTS: Among 23 patients,
      22 achieved hematopoietic recovery. The median time of ANC > 1.0 x 10(9)/L and
      BPC > 50 x 10(9)/L were + 13 (+ 11 - +17) days and + 30 (+13 + 102) days
      respectively. Two patients died of transplant related complications and three
      died of disease relapse, while 18 patients survived. Kaplan-Meier analysis showed
      disease free survival and relapse rate were (77.8 +/- 8.7)% and (14.4 +/- 7.5)%
      respectively. CONCLUSION: Allo-PBSCT is an effective treatment for MDS patients.

PMID- 17172125
TI  - [Comparison of clinical outcomes between unrelated donor peripheral blood stem
      cell transplantation and bone marrow transplantation for leukemia].
AB  - OBJECTIVE: To compare the hemopoietic reconstitution, immune reconstitution,
      infection, incidence of graft-versus-host disease (GVHD) and clinical outcome
      between unrelated donor peripheral blood stem cell (PBSC) transplantation and
      bone marrow (BM) transplantation for leukemias. METHODS: The clinical results of
      21 leukemia patients receiving G-CSF mobilized PBSC graft from unrelated donors
      were compared with that of 32 patients receiving unrelated BM transplants.
      RESULTS: Compared with BM grafts, the PBSC graft contained significantly more
      nucleated cells (P = 0.000), and resulted in a significantly shorter time-to
      neutrophil (12.43 +/- 3.67 vs 16.16 + 2.99 days) and platelet engraftment (14.67
      +/- 6.19 vs 21.23 +/- 8.25 days), (P = 0.000 and 0.003, respectively). T cell
      reconstitution between the two groups differed little after transplantation. The
      incidences of early-stage infection (42.86% vs 53.13%), the probabilities of
      acute graft-versus-host disease (aGVHD) (61.90% vs 71.88%), the grades III to IV
      aGVHD (23.81% vs 15.63%), the chronic GVHD (47.06% vs 43.48%) and the
      probabilities of relapse (6.90% vs 12.50%) between PBSC and BM groups all has no
      statistical significance (NS). The 2-year disease free survival (DFS) rates of
      the two groups were (50.14 +/- 12.00) % and (59.81 +/- 8.99)%, respectively also
      have no NS. CONCLUSION: G-CSF-mobilized unrelated donor PBSCs engraft more
      rapidly in the recipients as compared with conventional BM grafts. The T cell
      reconstitution, the incidence of infection, the incidence and severity of aGVHD
      and cGVHD, and the 2-year DFS rates between the two groups all have no
      significant differences.

PMID- 17172126
TI  - [Involvement of AKT/eNOS in brain derived neurotrophic factor-induced
      angiogenesis].
AB  - OBJECTIVE: To investigate the signaling pathways involved in brain derived
      neurotrophic factor (BDNF) -induced angiogenesis and to provide a novel pathway
      to anti-angiogenesis in multiple myeloma. METHODS: The phosphorylation of AKT and
      endothelial NO synthase (eNOS) in human umbilical venous epithelial cells (HUVEC)
      were detected by Western blot. The angiogenic activity in vitro was evaluated by
      transwell migration assay and tube formation assay. BDNF-induced in vivo
      angiogenic activity was evaluated by Matrigel plug assay. The concentration of NO
      was detected by nitric acid deoxidizase assay. Cell apoptosis was detected by
      FITC-Annexin V/PI double staining and flow cytometry. RESULTS: BDNF activated the
      phosphatidylinositol-3-kinase (PI3K)/AKT/eNOS pathway in HUVEC in a time- and
      dose-dependent manner. BDNF-stimulated NO production was blocked by LY294002, a
      PI3K inhibitor. In vitro, BDNF induced HUVEC migration and tube formation on
      Matrigel, which could be significantly blocked by LY294002 and N(G)-nitro-L
      arginine methyl ester (L-NAME) respectively; but BDNF induced HUVEC apoptosis
      could be blocked only by LY294002. In vivo, BDNF increased capillary ingrowth
      into subcutaneously implanted Matrigel plugs in mice, which could be
      significantly reduced in L-NAME treated mice. CONCLUSION: BDNF induces
      angiogenesis through the AKT/eNOS signaling kinase pathway. It may be a novel
      target for the anti-angiogenesis therapy for multiple myeloma.

PMID- 17172127
TI  - [Antisense oligonucleotide targeting endostatin enhances hematopoiesis
      reconstitution in BMT mice].
AB  - OBJECTIVE: To explore the effect of antisense oligonucleotide targeting
      endostatin (endostatin-ASON) transfecting bone marrow stromal cells ( BMSC) on
      hematopoiesis reconstitution in BMT mice. METHODS: Inhibition of endostatin /
      VCAM-1 protein and mRNA expression was investigated by transfection of antisense
      oligonucleotide targeting endostatin with confocal microscopy, Western blot and
      RT-PCR. Bone marrow stromal cells were cultured and divided into 4 groups: group
      (1) without any treatment; group (2) BMT only; group (3) BMT + endostatin-ASON
      transfection; group (4) BMT + endostatin scrambled sequence transfection.
      RESULTS: (1) Endostatin-ASON was successfully introduced into BMSC in vitro, and
      the transfecting rate was 86% ;(2) After Endostatin-ASON transfected into BMSC,
      the expression of Endostatin mRNA and its protein on the BMSC was signficantly
      inhibited at different time point after BMT [the grey value of Endostatin was
      (0.09 +/- 0.03) - (1.44 +/- 1.19) and (0.02 + 0.02) - (0.14 +/- 0.05),
      respectively] (P < 0.01 and P < 0.05); (3) Transfecting with Endostatin-ASON
      effectively promoted the expression of VCAM-1 mRNA and its protein on the BMSC
      [the gray value of VCAM-1 was (1.60 +/- 0. 92) - (8.05 +/- 0.87) and (0.07 +/-
      0.02) - (0.67 +/- 0.09) , respectively] (P <0.01 and P <0.05) ; (4) There was no
      effects of transfecting Endostatin scrambled sequence on the expression of
      Endostatin and VCAM-1 on the BMSC (P > 0.05). CONCLUSION: Endostatin-ASON could
      inhibit Endostatin expression and enhance VCAM-1 expression in BMSC after
      syngeneic-BMT in mice, which might be one of the mechanisms underlying the
      endostatin-ASON accelerating hematopoiesis reconstitution after allogeneic-BMT.

PMID- 17172128
TI  - [Effects of interleukin 13 on the differentiation and expression of transcription
      factor c-fos of HEL cells].
AB  - OBJECTIVE: To study the effects of IL-13 on the differentiation and expression of
      transcription factor c-fos of human erythroleukemia cell line (HEL) cells.
      METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to
      observe the mRNA expression of IL-13 receptor a 1, GP i b, vWF and c-fos, and
      Western blot and cytometry were used to analyse their protein expression.
      RESULTS: IL-13 receptor a 1 was expressed on HEL cells. IL-13 (100 ng/ml ) up
      regulated the mRNA expression of GP II b and vWF. The ratio of luminous
      absorption (LA) of GP I b to p-actin bands ( AB) was 1. 303 in control group,
      whereas was 2. 912 in experiment group; being 2. 23-fold higher than that in
      control group (P < 0. 05). The ratio of LA to AB for vWF was 0.217 in control
      group, and 0. 506 in experiment group; indicating a 2. 33-fold increase in
      experiment group (P <0. 05). The protein expression of GP I b and vWF was
      significantly increased in experiment group, compared with that in control group.
      IL-13 inducing the increased expression of c-fos mRNA and protein of HEL cells
      peaked at 30 min and 60 min, respectively. The ratio of LA to AB for c-fos was
      also increased at 30 min and 60 min (P <0. 05). CONCLUSION: IL-13 prompts the
      differentiation of HEL cells and up-regulates the expression of c-fos.

PMID- 17172130
TI  - [Prospective clinical study of diagnosis and classification for 282 cases with
      primary myelodysplastic syndrome].
AB  - OBJECTIVE: To summarize the diagnostic experience of primary myelodysplastic
      syndromes (MDS) in order to improve the diagnostic level. METHODS: Using
      prospective cohort study to collect consecutive samples. Diagnoses of 282 MDS
      cases were defined according to FAB and WHO classification. RESULTS: The median
      age at MDS onset was 56. 19.5% and 24.5% of cases occurred at age 50 - 59 and 70 
      79, respectively. Presence of immature granulocytes and erythroblasts in
      peripheral blood (PB) were found in 67% and 48% of the MDS patients,
      respectively. The percentage (68%) of FAB-RA and WHO-RCMD patients in China is
      relatively high compared to that in western countries. The abnormality of
      chromosome (31.2%) was lower than that in the West, and similar to that in Japan.
      Eighty nine percent of the MDS patients could be diagnosed on cell morphology in
      PB and bone marrow (BM) aspirate. Ninety four percent of MDS could be diagnosed
      by combination of BM aspirate and core biopsy. Ninety seven percent of the
      patients could be recognized by combination of bone marrow aspirate, core biopsy
      and cytogenetics. CONCLUSIONS: The subtypes and clinical features of Chinese MDS
      patients were somewhat different from the West, but similar to that in Japan.
      Diagnostic efficiency can be extremely improved by combination of bone marrow
      aspirate, core biopsy and cytogenetics.

PMID- 17172129
TI  - [Study on serum erythropoietin levels in patients with hematologic malignancies].
AB  - OBJECTIVE: To study whether hematologic malignancy patients with anemia have a
      lower erythropoietin (EPO) response. METHODS: Serum EPO levels were detected by
      ELISA in patients with hematologic malignancies and with iron deficiency anemia
      (IDA). Eighty patients with hematologic malignancies, including 13 multiple
      myeloma (MM), 7 chronic lymphocytic leukemia (CLL) and 60 non-Hodgkin's lymphoma
      (NHL) were studied. Thirty of them had anemia(21 NHL,6 MM and 3 CLL). Twenty
      patients with IDA were studied as the control. RESULTS: Hematologic malignancy
      patients with anemia had higher EPO levels [(97.8 +/- 183.9) IU/L] than those
      with normal Hb values [(27.8 +/- 85.4) IU/L; P <0.01]. In patients with IDA,
      serum EPO response was inversely correlated with Hb level (r= -0.5, P <0.05) ,
      but no such inverse correlation was found in the hematologic malignancy patients
      with anemia (r = -0.14). After corrected for Hb level, the serum EPO levels were
      significantly lower in anemic patients with hematologic malignancies than in IDA
      patients (P = 0.032) , indicating a decreased EPO response in the former group.
      CONCLUSION: Anemia associated with hematologic malignancy might result from an
      inappropriately low EPO response. EPO treatment for these patients may be
      beneficial.

PMID- 17172131
TI  - [Dangerous dogs in Berlin in comparison to the dog population--ways to reduce the
      dangerousness of dogs].
AB  - The law for handling and control of dogs in Berlin of September 29, 2004 was
      enacted to prevent the risks for humans and animals when ever they have contact
      with dogs. "Dangerous dogs" are defined by this law. There are 10 breeds of dogs
      supposed to be dangerous due to specific characteristics of their breed ("listed
      breeds"). The dangerousness of a dog's breed is not identical with the
      dangerousness of an individual dog. The subject of this study is to examine the
      potential dangerousness of dog breeds and not the individual dangerousness of a
      dog. This study refers to statistics of incidents between dogs and humans in
      Berlin for the years 1998 to 2004. The population density of a breed is based on
      the dogs assessed for tax purposes in Berlin of January 1, 2005 and on the dog
      registrations maintained at veterinary hospitals. The fourfold-table-test was
      used to compare the quantity of the recorded incidents of two statistically
      independent dog breeds. Of the total population of 107,804 tax assessed dogs in
      Berlin in 2004, 0.9% was documented as dogs involved in incidents with humans.
      The incidents per year decreased in the "listed breeds"about 68% and in the
      "unlisted breeds" about 41% during the last 7 years in Berlin. Therefore, the
      probability (the odds ratio) of a breed to be conspicuous was analysed. The
      values for the calculation of this probability were the number of dogs of a breed
      having been involved in incidents compared to the population of this breed based
      on tax records. The comparison of the probability of a breed with another to be
      conspicuous was used to compile a cluster of breeds which had the same
      probability to be conspicuous in 2004. A cluster was assessed for dogs of the
      following breeds: Sheep dogs, Rottweiler, Doberman, Pitbull Terrier and American
      Staffordshire Terrier. A listing of breeds is not the right way to reduce the
      potential dangerousness of a dog, especially in the private domain of their
      owners. Most incidents with dogs occur in the private domain which normally is
      not recorded in the statistics of incidents. Therefore, it is more effective to
      support activities which include the training of abilities of the dog owners.
      Training by experts can enable dog owners to avoid conflict situations with their
      dog, or in case of conflict, to take appropriate actions.

PMID- 17172132
TI  - Analysis of fluoroquinolone residues in edible chicken tissues using
      supercritical fluid extraction.
AB  - We evaluated a procedure that uses high-performance liquid chromatography to
      determine the levels of four fluoroquinolones (ciprofloxacin, enrofloxacin,
      norfloxacin, and ofloxacin) remaining in chicken breast muscle, liver, and
      kidneys after the analytes are extracted using supercritical fluid extraction
      (SFE). These antimicrobial fluoroquinolones were extracted by SFE using
      supercritical CO2 containing 30% (v/v) methanol. The recovery, limit of
      detection, accuracy, and precision of this method were evaluated on the basis of
      fortified matrices at concentrations of 25 to 250 microg/kg. The method is
      validated and shown to be linear in the range of 2.5-50 microg/kg. Spike
      recoveries for muscle, liver and kidney samples prepared at 4 spiking levels were
      ranged from 56.6-104.3%, 51.2-98.4% and 62.2-97.8%, respectively. The coefficient
      of variation (CV) for recovery as a measure of relative variability was between
      3% and 13%, and the relative standard deviation (RSD) was < 20%. The limits of
      quantitation (LOQ) were 10 microg/kg for enrofloxacin, 12.5 microg/kg each for
      ciprofloxacin and norfloxacin and 25 microg/kg for ofloxacin; these values were
      lower than the maximum residue levels (MRLs) authorized by the European
      Community. The 4 compounds were evaluated simultaneously, and the method was
      shown to be applicable for analyzing their residues in edible chicken tissues.

PMID- 17172133
TI  - [Use of new immunoglobulin isotype-specific ELISA-systems to detect Salmonella
      infections in pigs].
AB  - In Germany, the program for controlling salmonella infections in pigs is based on
      tests detecting salmonella-lipopolysaccharide (LPS) induced antibodies in meat
      juice or blood. These conventional tests which are based on the technology of
      enzyme-linked immunosorbent assay (ELISA) detect exclusively or mainly
      immunoglobulin(lg)G antibodies. Meanwhile, novel ELISA systems (WCE-ELISA, 3
      Isotype-Screening-ELISA) have been developed, which additionally detect the
      antibody classes IgM and IgA.This fact enables the registration of fresh
      salmonella infections (starting with day 5 p.i.) and thus, the distinction
      between early and older infections. The results show that animals with early
      salmonella infections appear significantly more often in herds with a high than
      with a low prevalence. With the newly developed tests this group of animals can
      be detected much more efficiently and precisely than with the tests used so far.
      Due to their clearly improved sensitivity the application of the WCE-ELISA and
      the 3-Isotype-Screening-ELISA in terms of the QS-Salmonella-Monitoring program
      can therefore significantly improve the selection of farms with potential
      salmonella excretors. Additionally, the WCE-ELISA can be applied very suitable
      for the examination of individual animals.

PMID- 17172134
TI  - [Occurence of salmonellae in laying hens in different housing systems and
      inferences for control].
AB  - As eggs represent now as ever the most important source for Salmonella infection
      in human beings and because of the currently occurring shift in housing
      conditions for laying hens from conventional cages to alternative systems it was
      studied whether the Salmonella prevalence in layers is influenced by the housing
      system. Following systems were considered: organic farming with free range
      management systems, floor management systems with free range, floor management
      systems without free range, conventional cages. 453 pooled faecal samples as
      single or double examination per herd from 329 flocks in different housing
      systems for table egg production from three Federal Lander were examined
      bacteriologically. The share of layer flocks which were Salmonella positive at
      least once independently of the housing system amounted to 32.2%. Analysis of the
      Salmonella findings in the single housing systems revealed that the share of
      Salmonella positive flocks was higher in conventional cage systems (46.3%) than
      in alternative housing systems (32.996% in organic farming with free range
      management systems, 21.9% in floor management systems with free range, 23.4% in
      floor management systems without free range). The results of the study clearly
      show that Salmonella Enteritidis (mostly phage type 4, other phage types rarely)
      presents with a share of 78% the dominant serovar in laying hens. The total
      number of all other serovars (apart from Salmonella Enteritidis and subspecies I
      rough) reached a share of ca. 14%, however, no other single serovar was dominant.
      As Salmonella Enteritidis is the predominant serovar in laying hens it is
      strongly recommended to use Salmonella Enteritidis vaccines for immunisation
      programmes of chickens during the rearing period. Because of the high prevalence
      of Salmonella organisms in the different housing systems, detailed information on
      the epidemiology of Salmonella in laying hens are needed to introduce effective
      control measures. Of particular interest is the question whether the Salmonella
      findings in laying flocks are the result of multiplication of already existing
      Salmonella organisms in the animals or whether the bacteria are introduced only
      during the laying period.

PMID- 17172135
TI  - [Appearance of multinucleated giant cells in association with an adenovirus
      infection in two guinea pigs].
AB  - In two guinea pigs (five years old, neutered male, and two and a half months old
      male, respectively) suffering from interstitial pneumonia, multinucleated giant
      cells were observed histologically in lungs, spleen and liver. The giant cells
      showed intranuclear, pale basophilic inclusions. Adenovirus could be demonstrated
      by electron microscopy.The multinucleated cells are supposed to be of histiocytic
      origin, since they contained variable amounts of haemosiderin in their cytoplasm.
      Formation of histiocyte-derived syncytia as a result of virus-induced cell fusion
      is discussed.

PMID- 17172136
TI  - Effects of long-term dietary supplementation of monensin or saccharomyces
      cerevisiae on blood acid-base and productive performance in growing feedlot
      steers.
AB  - The aim of this study was to evaluate the effects of two dietary supplements
      (monensin and a live yeast culture) on acid-base balance in steers maintained in
      a commercial feedlot system, considering effects over the growing period (14 to
      23 weeks of age). A 63-day feedlot study was performed using 42 double-muscled
      Belgian Blue steers. Steers were allotted randomly to one of the three study
      groups: (1) control group [no supplementation, C], (2) monensin supplementation
      [MON] at a concentration of 30 mg/kg (DM basis), and (3) live Saccharomyces
      cerevisiae strain supplementation [SACC] at a dose of 500 mg/kg (DM basis).
      Venous blood samples were collected for the measurement of acid-base parameters
      and L-lactate. Production parameters were also used as a complementary tool for
      understanding the internal changes associated with supplementation. Our results
      show that during the study period no statistical differences were observed
      between supplemented and control steers, although non-supplemented animals tended
      to gain more efficiently than those fed monensin or yeast. Nevertheless, taking
      into account blood parameters, these control animals showed a greater risk of
      acid overload due to a more marked decline in blood buffer levels over time in
      comparison with supplemented steers although no differences were observed between
      monensin or yeast supplemented animals. Additionally, significant effect of
      supplementation was observed in packed cell volume (PCV) values.

PMID- 17172137
TI  - [Influence of a xylanase feed additive on Lactobacillus species in the jejunum of
      piglets].
AB  - rRNA extracts from the jejunum of rearing piglets fed a wheat/rye based diet with
      or without a xylanase feed additive were hybridized against eight Lactobacillus
      spp. specific digoxigenin labelled oligonucleotide probes. Known concentrations
      of sample- or culture RNA extracts were used to calibrate and quantify
      hybridization signals from different sample extracts and hybridizations. The
      xylanase feed additive tended to increase total eubacterial rRNA in the terminal
      jejunum, probably a result of increased Lactobacillus spp. rRNA in the central
      and terminal jejunum. However, individual animal variations were high. L. reuteri
      was the major Lactobacillus species followed by L. acidophilus and L. mucosae. L.
      amylophilus and L. crispatus were not detected in all RNA extracts. The results
      of this study show that the xylanase feed additive modifies Lactobacillus spp.
      populations on the species level in piglets in addition to their well known
      effects on digesta viscosity and nutrient digestibility. The implications of
      these effects for the intestinal microbiota require further analysis.

PMID- 17172138
TI  - [Assessment of disease severity and outcome of dietary, antibiotic, and
      immunosuppressive interventions by use of the canine IBD activity index in 21
      dogs with chronic inflammatory bowel disease].
AB  - Recently, the canine IBD activity index (CIBDAI) was developed for evaluation of
      the severity of illness, therapeutic strategies, and efficacy of therapy. The aim
      of the present study was to assess the severity of illness and the therapeutic
      strategy in dogs with IBD by the use of CIBDAI, serum albumin concentration, and
      histologic score (HPEG). Furthermore the use of CIBDAI and the efficacy of
      therapy in a prospective study during a 3 month treatment period were evaluated.
      Twentyone dogs with inflammatory bowel disease (lymphocytic-plasmacytic enteritis
      and enterocolitis) were examined in this study. In 11 dogs with IBD the severity
      of illness was assessed as low, according to CIBDAI and HPEG (CIBDAI score 4 or
      between 5 and 10 with HPEG score between 1 and 1.5). Six dogs were treated with
      hypoallergenic diet (Group D), five dogs were treated with hypoallergenic diet
      and metronidazole (15.6-22,3 mg/kg/day) (Group M). In 10 dogs with IBD the
      severity of illness was assessed as high (CIBDAI <10, or CIBDAI between 5 and 10
      with HPEG score between 2 and 3 or hypoalbuminemia (< or = 2.5 g/dl)). This group
      (Group I) was treated with immunosuppressive therapy. Treatment consisted of
      prednisolone (n=10; 0.9-2 mg/kg/day), azathioprine (n=5; 0.9-2.3 mg/kg/day),
      sulfasalazine (n=4; 18.2-25 mg/kg/day) and hypoallergenic diet (n=10). Efficacy
      of therapy was evaluated prospectively 3 times in a 12 weeks treatment period.
      Remission (CIBDAI score < 4) indicated good therapeutic response, chronic or
      recurrent disease (CIBDAI score persistent or recurrent > or =4) indicated poor
      therapeutic response. Age, CIBDAI score and HPEG score were significantly
      different in IBD dogs with low severity of illness (age: median 60 months; CIBDAI
      score: median 5; HPEG score: median (1) and IBD dogs with high severity of
      illness (age: median 90 months; CIBDAI score: median 9.5; HPEG score: median
      2.25) (p = 0.0101 and p = 0.0099, respectively). The presence of hypoalbuminemia
      was not significantly different between these two groups (p = 0.3108). There was
      no significant correlation between CIBDAI score and serum albumin concentration
      (r = 0.0394; p = 0.0802) or between CIBDAI score and HPEG score (r = 0.2587; p =
      0.2574). In the treatment groups, HPEG score was only significantly different
      between D-group and group I (p < 0.01). The CIBDAI score decreased significantly
      in group I after 4 weeks of treatment (median 4th week: 3; p < 0.05), and in the
      D-group after 8 weeks of treatment (median 8" week 1; p < 0.05). No significant
      decrease of CIBDAI score was seen in the M-group (median 12th week: 1.75; p >
      0.05). All dogs in group D, four of five dogs in group M, and six from ten dogs
      in group I went into remission. Poor therapeutic response (1 dog in group M and 5
      dogs in group I; one dog died) was seen in 6 dogs, where as 15 dogs showed good
      therapeutic response. There was no significant association between efficacy of
      therapy and age (p = 0.8455), CIBDAI score (p = 0.3293), or serum albumin
      concentraton (p = 0.8455). Poor therapeutic response was weekly associated with
      HPEG score > or =2 (p = 0.0635). Using CIBDAI in dogs with IBD as a single
      parameter to assess the severity of illness and the therapeutic response,
      misinterpretations are possible. The assessment of the severity of illness by the
      combination of CIBAI, HPEG, and serum albumin concentration is leading to
      adaequate therapeutic results. Dogs with low grade IBD benefit from
      hypoallergenic diet, whereas dogs with high grade IBD benefit from
      immunosuppressive therapy. The effect of antibiotic treatment is questionable.

PMID- 17172139
TI  - [Comparative examination of the lateral cerebral ventricles of different dog
      breeds using quantitative computed tomography].
AB  - Due to the great variations among the shape of the skull in different breeds, the
      routine use of computed tomography in the diagnosis of central nervous diseases
      in the dog requires basic knowledge of the structure of the inner subarachnoidal
      spaces. In neoplastic as well as in inflammatory brain disease, changes of the
      size and shape of liquor filled spaces can be found. In the present study, the
      easily demonstrable lateral ventricles of the brain of ten dogs of each breed,
      respectively, without cerebral disease belonging to the breeds German Shepherd
      (DSH), Dachshund, Boxer, Labrador Retriever and Toy poodle were characterized
      with regard to their two-dimensional expansion. The average width and height of
      the lateral ventricles were ascertained for each breed. The Boxer had the
      relatively largest lateral ventricles, whereas in the other breeds,their sizes
      were very similar. 32 of the dogs investigated (64%) had symmetric lateral
      ventricles, and in 18 dogs (36%) they were asymmetric. Of these 18 cases, the
      left lateral ventricle was larger in 12 dogs (67%).

PMID- 17172140
TI  - [Follicle dynamics and characteristics of ovulation in heifers after Ovsynch
      treatment in the last third of the estrous cycle].
AB  - The objective of the experiment was to study follicular dynamics and
      characteristics of ovulations in dairy heifers after application of the Ovsynch
      protocol in the last third of estrous cycle. Therefore, altogether 27 regular
      cycling Holstein heifers were given an injection of GnRH on day 14, 16 or 18 (9
      heifers each in group 1 to 3) of the estrous cycle. All heifers were administered
      PGF2alpha seven days later. Blood was collected for progesterone determination,
      just before, 24 hours and 48 hours after the PGF2alpha injection. A second
      injection of GnRH was administered 48 hours after the PGF2alpha injection.
      Ovarian follicular dynamics were monitored by frequent ultrasound scanning of the
      ovaries after first and second GnRH injection. Altogether 22 of 27 heifers
      (81.5%) ovulated 27 to 33 h after first GnRH injection. In 4 heifers ovulations
      were recorded 45 to 51 h after first GnRH application. Mean intervals between
      GnRH application and ovulation were 33.0, 33.6 and 28.3 h, respectively. At the
      time of PGF2alpha injection mean progesterone concentrations were similar in
      groups 1 and 2, but significantly lower than in group 3. After the second GnRH
      treatment 5,6 and 8 heifers had ovulations. The average intervals from the second
      GnRH treatment to ovulation were 24.8, 24.0 and 24.4 h respectively. The results
      show that Ovsynch is not sufficient to ensure synchronisation of oestrous and
      ovulation in each animal treated.

PMID- 17172141
TI  - BoHV-1 eradication--one step closer.

PMID- 17172142
TI  - Estimating self, parental, and partner multiple intelligences: a replication in
      Malaysia.
AB  - Participants were 230 adult Malaysians who estimated their own, their parents',
      and their partners' overall IQs and 10 multiple intelligences. In accordance with
      both the previous literature and the authors' hypotheses, men rated themselves
      higher than did women on overall, verbal, logical-mathematical, and spatial
      intelligences. There were fewer gender differences in ratings of parents and in
      those of partners. Participants believed that they were more intelligent than
      both parents (but not their partners) and that their fathers were more
      intelligent than their mothers. Regressions indicated that participants believed
      that verbal intelligence and--to a lesser extent--logical-mathematical
      intelligence were the main predictors of overall intelligence. The authors
      discussed results in terms of the extant cross-cultural literature in the field.

PMID- 17172143
TI  - Who distinguishes between sinners and sins at the implicit level of awareness?
AB  - Several researchers have investigated the possibility that people indeed can love
      individuals who are engaged in behaviors that are considered unacceptable. In the
      present research, the authors evaluated the possibility that people distinguish
      between presumably sinful persons and presumably sinful behaviors at a cognitive
      level that does not involve conscious intent and awareness: the implicit
      (nonconscious) level of awareness. Participants performed a speeded-response
      task, the Implicit Association Test. Results indicated that participants were
      able to make such a (person vs. behavior) distinction and that in doing so, they
      manifested positive implicit evaluations of sinful people relative to sinful
      actions.

PMID- 17172144
TI  - Conditions of contact, common in-group identity, and in-group bias toward
      contingent workers.
AB  - In a survey-based field study of 111 permanent Finnish restaurant employees, the
      authors investigated intergroup relations between permanent and contingent
      workers. On the basis of the common in-group identity model, the authors
      hypothesized that the conditions of contact (supportive norms and perceived
      intergroup competition) would be related to common in-group identity, which in
      turn would be negatively related to intergroup bias. The present results
      indicated that perceived competition and institutional support were related to in
      group bias only through their influence on the common in-group identity, as the
      model predicted.

PMID- 17172145
TI  - The Janus face of power in intergroup contexts: a further exploration of the
      noblesse oblige effect.
AB  - The authors examined the impact of power on in-group bias by manipulating group
      members' power over the in-group and power over the out-group as orthogonal
      factors. Each factor had 3 levels: 0%, 50%, and 100%. Participants were 216 male
      pupils (12-13 years old). Participants showed no in-group bias when they had 0%
      control over the in-group, strong in-group bias with 50% control, but less in
      group bias with 100% control. Participants showed more in-group bias when they
      had 0% control over the out-group than when they had 50% or 100% control. The
      combination of these 2 main effects resulted in the noblesse oblige effect: Group
      members with complete control over both in-group and out-group expressed less in
      group bias than did group members who shared control with an out-group.

PMID- 17172146
TI  - Construed external image and organizational identification: a test of the
      moderating influence of need for self-esteem.
AB  - According to Social Identity Theory (cf., J. G. March & H. A. Simon, 1958),
      individuals tend to identify with prestigious or high-status groups. Researchers
      (J. E. Dutton, J. M. Dukerich, & C. V. Harquail, 1994) have revealed that
      organizational members also identify with organizations that have attractive
      public images. To gain a better understanding of the theoretical reasons
      underlying the relationship between image and identification in organizations,
      the authors examined this relationship in a healthcare setting. In addition, they
      investigated need for esteem as a moderator of the relationship between construed
      external image and organizational identification. Consistent with previous
      findings, the present results indicated that construed external image is
      positively related to organizational identification. Perhaps it is more important
      that the present findings also supported need for esteem as a moderator of the
      relationship between construed external image and organizational identification.

PMID- 17172147
TI  - Human-resource professionals' perceptions of organizational politics as a
      function of experience, organizational size, and perceived independence.
AB  - The author examined human-resource professionals' occupation-related and general
      work experience, socialization from participation in professional activities,
      organizational size, and perceived independence as predictors of perceptions of
      organizational politics (POPS). Results varied with the author's use of the
      overall POPS scale (K. M. Kacmar & G. R. Ferris, 1991) vs. a more specific
      subscale that measured perceptions related to such issues as pay- and promotion
      related politics. It was most notable that work experience appeared to have an
      inverse relationship with POPS among human-resource professionals in the area of
      pay and promotions. The author discussed results in relation to the implications
      and directions for future research.

PMID- 17172148
TI  - The role of authoritarianism, perceived threat, and need for closure or structure
      in predicting post-9/11 attitudes and beliefs.
AB  - The authors examined relationships among authoritarianism, personal need for
      closure or structure, perceived threat, and post-9/11 attitudes and beliefs.
      Participants were 159 undergraduate students in the Southeastern United States.
      The authors collected data 1 week before the U.S.-led invasion of Iraq in March
      2003. Correlation and regression analyses revealed that right-wing
      authoritarianism and social dominance orientation were significant predictors of
      support for restricting human rights during the U.S.-led War on Terror, support
      for U.S. President George W. Bush, and support for U.S. military involvement in
      Iraq. Right-wing authoritarianism and perceived threat emerged as the strongest
      predictors of the belief that Saddam Hussein supported terrorism.

PMID- 17172149
TI  - Authoritarianism among border police officers, career soldiers, and airport
      security guards at the Israeli border.
AB  - Several personality theories focusing on specific personality variables involved
      in career choice and job satisfaction are based on the assumption that
      individuals choose certain career choices because they believe that they may be
      able to meet their emotional needs (J. L. Holland, 1977). The author of this
      study investigated the personality traits of border police officers, career
      soldiers, and airport security guards in Israel. The participants were 160 men-
      40 border policemen, 40 career soldiers, 40 airport security guards, and 40
      control participants--who filled out a demographic questionnaire and a Hebrew
      version of the right-wing authoritarianism (RWA) shortened scale (B. Altemeyer,
      personal communication, February 2000). The present hypothesis predicted that the
      RWA scores of border police officers would be the highest, followed by those of
      career soldiers, airport security guards, and control participants, in that
      order. Statistically significant differences in RWA scores occurred between these
      groups in the predicted order, with the exception of the career soldiers' RWA
      scores, which did not significantly differ from those of the airport security
      guards.

PMID- 17172150
TI  - Molecular imaging with PET--open questions?
AB  - Molecular imaging has become a very popular term in medicine and can be
      interpreted in many different ways. It is argued that a correct definition should
      be 'in vivo imaging of biological processes with appropriate molecular probes'.
      The real challenge in molecular imaging therefore is the search for the 'optimal'
      molecular imaging probes. It is discussed that nuclear, optical and magnetic
      probes can be used. However, only PET probes have the high sensitivity to be
      applied generally. To develop PET probes efficiently, methods for the in vitro
      and in vivo characterization are discussed and alternatives compared. Some open
      questions with respect to the reliability of animal imaging and evaluation of the
      imaging data will be elucidated.

PMID- 17172151
TI  - Fluorine-18 labeling methods: Features and possibilities of basic reactions.
AB  - Many experimental and established tracers make fluorine- 18 the most widely used
      radionuclide in positron emission tomography with an increasing demand for new or
      simpler 18F-labeling procedures. After a brief summary of the advantages of the
      nuclide and its major production routes, the basic features of the principal
      radiofluorination methods are described. These comprise direct electrophilic and
      nucleophilic processes, or in case of more complex molecules, the labeling of
      synthons and prosthetic groups for indirect built-up syntheses. While addressing
      the progress of no-carrier-added 18F-labeling procedures, the following chapters
      on more specific topics in this book are introduced. Emphasis is given to
      radiofluorination of arenes--especially with iodonium leaving groups. Examples of
      radiopharmaceutical syntheses are mentioned in order to illustrate strategic
      concepts of labeling with fluorine-18.

PMID- 17172152
TI  - Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides
      derived from no-carrier-added [18F]fluoride as labeling precursors.
AB  - The favourable long-half life, the ease of production and the low energy of the
      emitted positron make 18F an ideal radionuclide for PET imaging. Radiochemistry
      of 18F basically relies on two distinctive types of reactions: nucleophilic and
      electrophilic reactions. All syntheses of 18F-labeled radiotracers are based on
      either [18F]fluoride ion or [18F]fluorine gas as simple primary labeling
      precursors which are obtained directly from the cyclotron. They can be applied
      either directly to the radiosynthesis or they can be transformed into more
      complex labeling precursors enabling the multi-step build-up of organic tracer
      molecules. The topic of this review is a survey on the application of several 18F
      labeled aryl fluorides as building blocks derived from no-carrier-added (n.c.a.)
      [18F] fluoride to build up small monomeric PET radiotracers at high specific
      radioactivity by multi-step synthesis procedures.

PMID- 17172153
TI  - Fluorine-18 labeling of peptides and proteins.
AB  - The pool of promising peptides worthy of investigation and evaluation for
      clinical use is continuously filled from different sources. Driven by the
      promising results obtained with peptides addressing somatostatin-2 receptor
      positive (sst2+) neuroendocrine tumours, other peptides targeting further
      receptor systems are being studied and evaluated. Progress in profiling the
      density and incidence of peptide hormone receptors in human cancer has initiated
      and will further promote research on the corresponding peptidic binders. In
      addition, industrial pharmaceutical research will be another significant source
      of peptides in the future. A recent prognosis revealed that about 50% of the
      drugs entering clinical trials in the next years will be peptides. The extensive
      research activities in genomics and proteomics will point out and quantify new
      and already known target structures upregulated in specific diseases. Based on
      the knowledge of their endogenous ligands or via selection of suitable candidates
      by phage display, suitable peptide ligands for e.g. membrane associated receptors
      can be identified and thus allow targeting of such binding sites. Thus, bioactive
      peptides specifically addressing relevant molecular targets are expected to
      become an important class of tracers, also due to the possibility of bridging
      imaging with therapeutic approaches. In this brief overview a summary of methods
      and strategies for the 18F-labeling of peptides and proteins is given.

PMID- 17172154
TI  - [18F]fluoropyridines: From conventional radiotracers to the labeling of
      macromolecules such as proteins and oligonucleotides.
AB  - Molecular in vivo imaging with the high-resolution and sensitive positron
      emission tomography (PET) technique requires the preparation of a positron
      emitting radiolabeled probe or radiotracer. For this purpose, fluorine-18 is
      becoming increasingly the radionuclide of choice due to its adequate physical and
      nuclear characteristics, and also because of the successful use in clinical
      oncology of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), which is currently the
      most widely used PET-radiopharmaceutical and probably the driving force behind
      the growing availability and interest for this positron-emitter in
      radiopharmaceutical chemistry. With a few exceptions, radiofluorinations
      involving fluorine-18 of high specific radioactivity (e.g. > 185 GBq/micromole)
      had, until recently, been limited to nucleophilic substitutions in homoaromatic
      and aliphatic series with [18F]fluoride. Considering chemical structures showing
      a fluoropyridinyl moiety, nucleophilic heteroaromatic substitution at the ortho
      position with no-carrier-added [l8F]fluoride, as its K[18F]F-K222 complex,
      appears today as a highly efficient method for the radiosynthesis of radiotracers
      and radiopharmaceuticals. This chapter summarizes the recent applications of this
      methodology and highlights its potential in the design and preparation of, often
      drug-based, fluorine-18-labeled probes of high specific radioactivity for PET
      imaging, including macromolecules of biological interest such as peptides,
      proteins and oligonucleotides.

PMID- 17172155
TI  - Production of non-standard PET radionuclides and the application of
      radiopharmaceuticals labeled with these nuclides.
AB  - The field of positron emission tomography (PET) has expanded dramatically over
      recent years. In spite of this expansion the large majority of clinical studies
      are carried out utilizing one radiopharmaceutical-2-fluoro-2-deoxyglucose. Many
      research groups are developing novel radiopharmaceuticals. A major emphasis is on
      other agents labeled with 18F. Several other positron emitting radionuclides can
      be prepared in high yields in small biomedical cyclotrons. Some of these have
      half-lives that make delivery significantly easier than the delivery of 18F
      compounds. These radionuclides include: 64Cu (half life 12.7 h), 76Br (half life
      16.2 h), 86Y (half life 14.74 h) and 124I (half life 4.2 days). The method of
      production of these and other 'non-standard' PET radionuclides will be discussed
      and the method of labeling radiopharmaceuticals with these radionuclides
      described. Several of these radiopharmaceuticals have been studied in animal
      models as well and a limited number translated to the human situation.

PMID- 17172156
TI  - Carbon-11 labeling chemistry based upon [11C]methyl iodide.
AB  - Radiochemistry with the short-lived positron emitter 11C (half-life 20.38 min)
      represents special challenges in terms of synthesis time and labeling techniques.
      The recent developments in 11C radiochemistry have steadily expanded the number
      of 11C labeled compounds. This chapter addresses selected chemical and technical
      aspects of 11C chemistry based on the readily available labeling precursors [11
      C]methyl iodide and, to a lesser extent, [11C]methyl triflate. Special emphasis
      is placed on heteroatom methylation reactions and 11C-C bond formations.

PMID- 17172157
TI  - 68Ga-PET radiopharmacy: A generator-based alternative to 18F-radiopharmacy.
AB  - Positron emission tomography (PET) is becoming a dominating method in the field
      of molecular imaging. Most commonly used radionuclides are accelerator produced
      11C and 18F. An alternative method to label biomolecules is the use of metallic
      positron emitters; among them 68Ga is the most promising as it can be produced
      from a generator system consisting of an inorganic or organic matrix immobilizing
      the parent radionuclide 68Ge. Germanium-68 has a long half-life of 271 days which
      allows the production of long-lived, potentially very cost-effective generator
      systems. A commercial generator from Obninsk, Russia, is available which uses
      TiO2 as an inorganic matrix to immobilize 68Ge in the oxidation state IV+.
      68Ge(IV) is chemically sufficiently different to allow efficient separation from
      68Ga(III). Ga3+ is redox-inert; its coordination chemistry is dominated by its
      hard acid character. A variety of mono- and bifunctional chelators were developed
      which allow immobilization of 68Ga3+ and convenient coupling to biomolecules.
      Especially peptides targeting G-protein coupled receptors overexpressed on human
      tumour cells have been studied preclinically and in patient studies showing high
      and specific tumour uptake and specific localization. 68Ga-radiopharmacy may
      indeed be an alternative to 18F-based radiopharmacy. Freeze-dried, kit-formulated
      precursors along with the generator may be provided, similar to the 99Mo/99mTc
      based radiopharmacy, still the mainstay of nuclear medicine.

PMID- 17172158
TI  - Microwaving in F-18 chemistry: quirks and tweaks.
AB  - Since the late 1980s, microwave dielectric heating has been used to speed up
      chemical transformations, also in radiolabeling tracers for positron emission
      tomography. In addition to shorter reaction times, higher yields, cleaner product
      mixtures and improved reproducibility have also been obtained for reactions
      involving polar components that require heating at elevated temperatures. The
      conditions used in microwave chemistry can differ considerably from those in
      conventional heating. Understanding the factors that influence the interaction of
      the electromagnetic field with the sample is critical for the successful
      implementation of microwave heating. These parameters are discussed here and
      exemplified with radiolabelings with fluorine-18.

PMID- 17172159
TI  - Micro-reactors for PET tracer labeling.
AB  - Miniaturization of PET radiosynthesis devices (micro-reactors or microfluidic
      systems) is an emerging area that has the potential to deliver many advantages,
      such as more efficient use of hot-cell space for production of multiple
      radiotracers; use of less non-radioactive precursor for saving precious material
      and a reduced separation challenge; highly controlled, reproducible and reliable
      radiotracer production; and cheap, interchangeable, disposable and quality
      assured radiochemistry processors. Several 'proof of principle' examples along
      with basics of micro-reactor flow control, mixing principle and design, and
      device fabrication are discussed in this chapter.

PMID- 17172160
TI  - Synthesis modules and automation in F-18 labeling.
AB  - Fast implementation of PET into clinical studies and research has resulted in
      high demands in the automated modules for the preparation of PET
      radiopharmaceuticals in a safe and reproducible manner. 18F-labeled radiotracers
      are of considerable interest due to longer half-life of fluorine-18 allowing
      remote site application, as demonstrated by [18F]FDG. In this chapter, the state
      of the art of commercially available modules for [18F]FDG is reviewed with the
      emphasis on multibatch production of this important radiotracer. Examples are
      given on the syntheses of other clinically relevant 18F-labeled radiotracers by
      using existing [18F]FDG synthesizers or with the help of general-purpose
      [18F]nucleophilic fluorination modules. On-going research and progress in the
      automation of complex radio labeling procedures followed by development of
      flexible multipurpose automated apparatus are discussed. The contribution of
      radiochemists in facilitating automation via introduction of new 18F-labeling
      techniques and labeling synthons, on-line reactions and purifications etc. is
      outlined.

PMID- 17172161
TI  - Pharmacological prerequisites for PET ligands and practical issues in preclinical
      PET research.
AB  - The development of PET radiopharmaceuticals for the non-invasive imaging of
      cancerous lesions, brain receptors, transporters and enzymes started more than 25
      years ago. But till today no established algorithms exist to predict the success
      of a PET radiopharmaceutical. PET radioligand development is a challenging
      endeavor and predicting the success of PET ligand can be an elusive undertaking.
      A large number of PET radiopharmaceuticals have been developed for imaging, but
      so far only a few have found application as imaging agents in vivo in humans.
      Typically, the potential compound selected for development usually has the
      desired in vitro characteristics but unknown in vivo properties. The purpose of
      this chapter is to highlight some of the pharmacological constraints and
      prerequisites. Interspecies difference in metabolism and mass effects are
      discussed with examples. Finally, some of the practical issues related to
      laboratory animal imaging using anesthetic agents are also presented.

PMID- 17172162
TI  - Positron emission tomography imaging as a key enabling technology in drug
      development.
AB  - The use of positron emission tomography (PET) in drug development has become more
      common in the pharmaceutical industry in recent years. One of the biggest
      challenges to gaining acceptance of this technology is for project teams to
      understand when to use PET. This chapter reviews the usage of PET in drug
      development in the context of target, mechanism and efficacy biomarkers. Examples
      are drawn from a number of therapeutic areas, but we also show that the relative
      penetration of this technology beyond CNS and oncology applications has been
      relatively small. However, with the increasing availability of PET and
      development of novel radiotracers it is expected that the utilization will be
      much broader in future years, with the additional expectation that the use of PET
      as an efficacy biomarker will also become more evident.

PMID- 17172163
TI  - [Fundamental biological model for trials of wound ballistics].
AB  - The aim of our experiment was the testing of effects of common ammunition on
      usable and slightly accessible biological tissue thereby to create fundamental
      simple biological model for trials of wounded ballistic. Like objective tissue
      was elected biological material - pork and beef hind-limbs, pork head, pork
      bodily cavity. It was discovered that objective tissue is able to react to
      singles types of shots in all spectrum results namely simple smooth penetration
      wound as well as splintery fracture in dependence on kind of using ammunition.
      Pork hind-limb was evaluated like the most suitable biological material for given
      object.

PMID- 17172164
TI  - [Screening and identification of stimulant and psychedelic drugs as acetyl
      derivatives by GC-MS].
AB  - With the increasing number of abused stimulant and psychedelic drugs, along with
      so called "dance drugs" and "new synthetic drugs" available on the Czech illegal
      market, there is a need to update methods in toxicological laboratories and
      therefore it is necessary to develop and optimalize screening and identification
      procedures for new toxic substances appearing in the laboratory practice. It is
      well known that relatively popular commercial screening immunoassays have some
      limits: for instance restricted amount of detectable substances, specificity and
      sensitivity of detection. Therefore, it is mandatory to combine or complete them
      with more specific methods based on a different principle. In this paper we have
      focused on collecting useful analytical data to introduce or complete the system
      of detection and identification of unknown drugs and their metabolites which can
      appear in biological samples by using gas chromatography-mass spectrometry (GC
      MS) after preparation of relevant acetylated derivatives. The collection of
      experimental data involves retention indexes and mass spectra of acetylated
      phenylalkylamines, tryptamines and piperazines and some of their metabolites.
      These data are fundamental for laboratory diagnostics of drugs of abuse or
      intoxication and they can be useful for practical application in a number of
      toxicological laboratories. The mean limit of detection 0.1 ng analyte injected
      to GC-MS is low enough to allow the method to be successfully applied to real
      toxicological samples.

PMID- 17172165
TI  - [Mineral substance in human nutrition. Manganese: absorbtion and
      bioavailability].
AB  - The review is presented data on absorption and bioavailability of manganese in
      humans and laboratory animals, as well as the food factors that affect on these
      processes. There are described the mechanisms of control homeostase of manganese
      by two main paths: gastrointestinal absorption and excretion via bile. Presented
      findings define the absorption of manganese as a complex physiological process.
      The role is discussed of a series of the food factors, first of all iron, as well
      as fibers, phytates, calcium and some other components of food in absorption and
      bioavailability of manganese.

PMID- 17172166
TI  - [Mineral substance in human nutrition. Selenium: absorption and bioavailability].
AB  - In the review there are discussed results of selenium absorption studies in human
      and animals gastrointestinal tract. According to plenty of experimental data
      selenate-anion is rapidly and quantitatively absorbed upstream concentration
      gradient the site of absorption being predominantly ileum. This process is Na+
      and energy dependent. On the contrary seleniteanion is absorbed mostly in
      jejunum, the rate of uptake is less than for selenate in model systems and
      absorption does not occur toward concentration gradient. Under physiological
      conditions the most part of selenite is transported as mixed thiols with
      glutathione and some other tissue thiol compounds. Selenium amino acids are
      transported by corresponding transfer systems with specificity for analogous
      sulfur containing amino acids. Whereas bioavailability of transition al metals
      salts rarely exceeds 10-20%, selenium food sources (both organic and inorganic
      origin) are typically high absorbable predominantly on 60% or more and in some
      cases almost on 100%. From this point of view selenium food sources
      bioavailability evaluation must take into account their metabolic retention and
      toxicity indicies rather than absorption ratio (such is for zinc, chromium and
      other metal ions).

PMID- 17172167
TI  - [The influence of ambulatory tested hypocaloric diet on biochemical indexes of
      patients of different ages suffering from obesity].
AB  - 2-5 months-lingth ambulatory tested hypocaloric diet in patients mith obesity
      makes for normalization of lipid, hydrocarbon metabolism, as creatinine and uric
      acid in blood against the background of patients body weight reduction.

PMID- 17172168
TI  - [Influence of wholemeal bread on functional and structure characteristics
      erythrocytes membrane and lipids oxidation in fraction of microsome of internal
      organs in rats].
AB  - Acute tests in rats showed, that application of wholemeal bread into a standard
      vivarium ration (40 g per a rat with body weight 180-200 g) drastically impoves
      structural and functional characteristics of membranes of erlthrocytes and cells
      of a number of internal organs. Anhibition of peroxide oxidation of biological
      membranes lipids of internal organs (liver, ridneys, heart, lungs and brain)
      takes place, as well as impairment of erythrocytes membranes perkeability and
      increase of their peroxide resistivity.

PMID- 17172169
TI  - [Multivitamin-mineral complexes: types, means of intake, efficiency].
AB  - Comparison of intake efficiency of the multivitamin-mineral complexes containing
      all micronutrients in the same tablet, has not revealed negative influence of
      microelements on vitamin status improvement. Thus, not denying an opportunity of
      existence and advantage of intake of vitamin-mineral complexes in which
      components are divided on different tablets, it is necessary to recognize, that
      from demonstrative medicine positions no sensible arguments in favour of vitamins
      and minerals availability improvement and, hence, the raised efficiency of such
      complexes usage has been yet found. Specially planned researches considering
      dozes, forms of mineral substances, equivalence of groups etc. are necessary for
      a final conclusion about compatibility or incompatibility of separate components
      in a tablet.

PMID- 17172170
TI  - [Efficiecy of application assessment of grain bread in diettherapy of patients of
      elderly ages with cardiovascular diseases].
AB  - It was investigated the influence of a diet supplemented with grain bread on
      dynamic and of lipid profile metabolism in patients with ischemic heart disease,
      hypertension and hyperlipoproteidemia. It was shown that antiaterosclerotic diet
      with including bread has promoted the most positive changes of the hypertension
      and serum cholesterol.

PMID- 17172171
TI  - [Clinicohemadynamic and biochemical the effect of patients with coronary heart
      disease use combinated lactoovovegetarian diets and simvastatin].
AB  - This work is aimed at studying the effect of a lactoovovegetarian antiatherogenic
      well-balanced diet, combined with the hypolipidemic drug simvastatin, on
      clinicohemodynamic and biochemical parameters of patients with coronary heart
      disease and pronounced hypercholesterolemia (TC > 7.8 mmol/l). 43 patients
      suffering from coronary heart disease, stenocardia under loading (functional
      classes II-IV) were observed. The patients of the first group (n=17) were had an
      antiatherogenic vegetarian diet, the patients of the second group (n=26) had the
      antiatherogenic mixed diet IOC. Besides a standard antianginal therapy all the
      patients received simvastatin in a daily doze of 20 mg. By the end of the treat
      ment positive changes in clinicogemodynamic and biochemical parameters were
      methobolism lipid observed in both the groups of patients. The comparison of
      lipid parameters revealed a significant and reliable decrease in the first group.

PMID- 17172172
TI  - [Effect of antioxidant use in dietary therapy in patients with chronic athrofic
      hastritis].
AB  - In the 1-year double-blind placebo-controlled intervention trial, it was shown
      that daily supplementation of patients with gastric premalignant lesions
      (intestinal metaplasia, IM) with a complex, containing Ester-C with
      antioxidantsand (2100 mg of Ca-ascorbate + 340 mg of bioflavonoids), produced a
      sharp decrease of abnormally high ornithine decarboxylase activity in IM gastric
      mucosa that was accom panied by practically total IM regression in 11 of 18 (61%)
      patients.

PMID- 17172173
TI  - [The analysis risk of contamination microorganism food products].
AB  - Analytical review presents the specific issues of the analysis (AMR as concept)
      and an microbiological risk assessment (MRA as process). The AMR structure as a
      whole, its role and advantages in system of a current food safety assessment
      system, and also existing problems of accu mulation of the risk-oriented
      information are covered. The methodology of MRA is described, the characteristic
      of its subelements, the primary goals and means of their performance at each
      stage of process is given. Article is illustrated by own examples of the
      determination of the numbers/quantities of coliforms and E. coli ingested by the
      consumers weith large consumption products and also of the modular process risk
      modelfor VT-E. coli in semifinished meat.

PMID- 17172174
TI  - [Ochratoxin A content in baby food].
AB  - The purpose of this study was to investigate the ochratoxin A content in baby
      food. The analysis of ochratoxin A were performed by immunoaffinity column clean
      up and HPLC with fluorescence detection. The detection limit was 0.2 mg/kg.
      Ochratoxin A was detected in 22.5% of 40 samples up to 1.2 mg/kg. Mean level was
      0.15 and 0.31 mg/kg. Ochratoxin A level was higher in oat-based samples.
      Calculations made on the basis of the obtained means showed that the daily
      ochratoxin A dietary intake were up to 1.72 ng/kg b.w.

PMID- 17172175
TI  - [The immune-enhancing effects of oral administration of strains bifidobacteria in
      experiments].
AB  - This paper reviews evidence for the immune-enhancing effects of probiotics. The
      influence of bifidobacteria B. lactis 668 and B. lactis BB12 on the immune
      functions and the structure of peripheral lymphoid organs in male Wistar rats was
      investigated after 3 weeks feeding. Rats were oral administrated with
      bifidobacteria x 10(7) CFU/sm3. The rats of control group had no feeding any
      probiotics. This is evidence that probiotic bacteria improve host immune
      function: cell-mediated and humoral immunity in rats. The increased activity of
      peritoneal macrophages was confirmed by enhancement superoxid anion pro duction
      that leads to improving unspecific resistance of organism. The immunostimulatory
      effects of probiotics was also confirmed by morphological investigation of
      peripheral lymphoid organs.

PMID- 17172176
TI  - Modern neuropsychology in France: Alajouanine's painter.

PMID- 17172177
TI  - Efficacy of visuo-spatial training in right-brain damaged patients with spatial
      hemineglect and attention disorders.
AB  - Several rehabilitative approaches have been used to reduce neglect disorders.
      Some studies tried to demonstrate that hemineglect can be ameliorated by using
      tasks promoting attentional activation towards the neglected hemispace (Robertson
      et al., 1995, 2001). As a consequence, a functional link between level of
      attention and disorders of space exploration has been proposed. For this reason
      we tried to explore the possible role of attentional deficits on the efficacy of
      a standard neglect treatment based on visuo spatial rehabilitation. In this study
      we then examined the performances of a selected group of seven right brain
      damaged patients, suffering from both severe hemineglect and attentional deficits
      (of both phasic and tonic components of attention), to several tasks before and
      after a visuo-spatial training (VST) whose efficacy has been already demonstrated
      (Pizzamiglio et al., 1992). Results showed that VST induces a significant
      remission of hemineglect symptoms independently from disorders of attention.
      Moreover, after visuo-spatial rehabilitation, no improvement of attentional
      deficits is detectable.

PMID- 17172179
TI  - Preserved conceptual priming in Alzheimer's disease.
AB  - We assessed Alzheimer's disease (AD) and healthy older adult control (HC) group
      performance on: (1) a conceptual priming task, in which participants had to make
      a semantic decision as to whether a degraded picture of an object encountered
      previously belonged to the category of living or non-living things; and (2) a
      recognition memory task. The AD group showed a dissociation between impaired
      performance on the recognition task and preserved priming for semantic decisions
      to degraded pictures. We argue that it is not whether priming is conceptual or
      perceptual that is important for the observation of priming in AD, rather it is
      the nature of the response that is required (c.f., Gabrieli et al., 1999).

PMID- 17172178
TI  - Variability in the impairment of recognition memory in patients with frontal lobe
      lesions.
AB  - Fourteen patients with frontal lobe lesions and 14 normal subjects were tested on
      a recognition memory task that required discriminating between target words, new
      words that are synonyms of the targets and unrelated distractors. A deficit was
      found in 12 of the patients. Moreover, three different patterns of recognition
      impairment were identified: (I) poor memory for targets, (II) normal hits but
      increased false recognitions for both types of distractors, (III) normal hit
      rates, but increased false recognitions for synonyms only. Differences in terms
      of location of the damage and behavioral characteristics between these subgroups
      were examined. An encoding deficit was proposed to explain the performance of
      patients in subgroup I. The behavioral patterns of the patients in subgroups II
      and III could be interpreted as deficient post-retrieval verification processes
      and an inability to recollect item-specific information, respectively.

PMID- 17172180
TI  - Mental rotation test performance in four cross-cultural samples (n = 3367):
      overall sex differences and the role of academic program in performance.
AB  - Two meta-analyses (Linn and Petersen, 1985; Voyer et al., 1995) discuss variables
      that affect mental rotation performance but they do not mention a potentially
      important variable, the Academic Program in which students are enrolled. Sex
      differences in brain size have been related to sex differences in spatial
      performance (e.g., Falk et al., 1999) and thus it is important to know whether
      mental rotation performance shows a significant interaction between Sex and
      Academic Program. To put our understanding of the Academic Program effect on a
      firmer empirical footing, we conducted a large scale multicultural study, with
      samples from Canada, Germany and Japan, using identical test procedures in all
      studies. Significant main effects for Sex and Academic Program were found in all
      four studies, with large effect sizes for Sex and medium to large effect sizes
      for Academic Program (based on Cohen's d). No significant interactions between
      these variables were found in the four samples. Our demonstration of a reliable
      Academic Program effect has clear and important pragmatic implications for a
      broad range of work on spatial ability and its interpretation.

PMID- 17172181
TI  - Attentional dysfunction of the central executive in AD: evidence from dual task
      and perseveration errors.
AB  - This study examined the capacity of 27 Alzheimer's disease (AD) patients to
      divide attention between two simultaneous tasks, as compared to 27 elderly
      controls. In order to determine whether distribution of attention is affected by
      age, a younger group was included. The results showed a marked impairment in the
      capacity of the AD patients to combine performance in two simultaneous tasks
      compared to the elderly controls, but the latter group did not differ from the
      younger participants, indicating a disease rather than an age effect, and
      replicating the results of Baddeley et al. (2001). The present study also
      analysed whether perseverations committed in a previous study (Sebastian et al.,
      2001) by some AD and elderly control participants in the Brown-Peterson (B-P)
      task (Brown, 1958; Peterson and Peterson, 1959) were related to their attentional
      capacity in the dual task. Although the elderly controls committed perseveration
      errors, a negative correlation was only found in the AD group between the index
      of attention distribution in the dual task and the frequency of perseverations in
      the B-P task. Our results would therefore suggest that AD patients show a
      dysfunction of the central executive and/or a deficit in their ability to
      allocate cognitive resources. This could be interpreted in terms of problems in
      updating the contents of working memory and suppressing activation of no-longer
      relevant information in the early stages of AD, leading to perseveration errors
      in the B-P task.

PMID- 17172182
TI  - Lexical processing in illiteracy: effect of literacy or education?
AB  - Difficulties in phonological processing in illiterates have been attributed to
      their limited phonological awareness, a consequence of their lack of literacy. We
      sought to explore the potential influence of education on auditory lexical
      processing above and beyond literacy per se. In order to achieve this goal, we
      compared a lexical decision making paradigm with a repetition paradigm using
      words and pseudo-words. We based this choice of tasks on previous research, which
      has shown that pseudo-word repetition is dependent on the phonological loop; such
      studies have thus demonstrated a literacy effect on repetition. Instead, lexical
      decision making is known to depend on the size of one's vocabulary, which is
      influenced by the level of education attained. Our sample comprised three groups:
      illiterate no education, literate/low education and literate/high education,
      individuals. The pattern of our findings confirmed that literacy has an effect on
      the capacity of the phonological loop, as our illiterate group alone had
      difficulty with repetition, as compared with both literate/educated groups. Also,
      our findings suggested an education effect on lexical decision making, as we
      found a gradation in the performance of the three groups. Therefore, we succeeded
      in dissecting the effect of literacy and education on auditory lexical processing
      through the application and comparison of two simple paradigms.

PMID- 17172184
TI  - Respiratory effects of surgery and pulmonary function testing in the preoperative
      evaluation.
AB  - Advanced age, smoking habit, obesity or malnutrition, the coexistence of
      hypercapnia, bronchospasm or bronchial hypersecretion, the lack of pre-operative
      preparation and/or a prolonged duration of anaesthesia can negatively influence
      respiratory function in patients undergoing abdominal or thoracic surgery.
      Spirometric testing of pulmonary function is recommended in patients with a
      history of tobacco use or dyspnoea who are considered for cardiac or upper
      abdominal surgery and for all patients who are candidated for lung resection.
      Spirometry can provide cut-off values of acceptable risk in patients that are
      candidated for abdominal and thoracic surgery. At-risk patients having resective
      lung surgery should undergo a split lung function study with quantitative lung
      scanning or computed tomography in order to estimate the function of residual
      parenchyma after surgery. In patients with borderline estimated values, a
      cardiopulmonary exercise test is useful to further stratify surgical
      risk.(www.actabiomedica.it)

PMID- 17172183
TI  - In defense of the lexical-competition account of picture-word interference: a
      comment on Finkbeiner and Caramazza (2006).
AB  - On the basis of two empirical observations, Finkbeiner and Caramazza (2006) take
      issue with the generally accepted interpretation of semantic interference in the
      picture-word interference task in terms of lexical competition. As an
      alternative, they propose a response-selection account, in which semantic
      interference is attributed to the time needed to remove the inappropriate (word
      reading) response from an output buffer. In this comment we argue that the
      empirical work discussed provides an interesting challenge for current models of
      language production, but that the authors' alternative account is at variance
      with at least three robust empirical findings in the language production
      literature.

PMID- 17172185
TI  - Comparison between two real-time PCR assays and a nested-PCR for the detection of
      Toxoplasma gondii.
AB  - BACKGROUND AND AIM OF THE WORK: In recent years, the diagnosis of toxoplasmosis
      has been improved by Real-time PCR assays. In this study we compared the
      performances of two Real-time PCRs (FRET and TaqMan protocols) already described
      in the literature, and one nested-PCR, currently used in our laboratory for the
      molecular diagnosis of toxoplasmosis. METHODS: We evaluated the sensitivity and
      the specificity of a FRET- and a TaqMan-based Real-time PCRs targeting a 529 bp
      repeat region and the 18S RNA gene, respectively, and a nested-PCR, targeting the
      B1-gene of Toxoplasma gondii. We also tested, through nested-PCR, 46 biological
      samples obtained during a period of 29 months from pregnant women or
      immunocompromised patients with suspected T. gondii infection. RESULTS: The
      analytical sensitivity of nested and TaqMan PCRs was approximately 10(3)
      tachyzoites/ml. FRET assay showed a sensitivity of 102 tachyzoites/ml. Three out
      of 46 biological samples were nested-PCR-positive and these results were also
      confirmed by both Real-time PCRs. CONCLUSIONS: Nested- and real-time PCRs
      evaluated in this study resulted very sensitive and specific; in particular FRET
      PCR resulted more sensitive than the other assays, probably because of the
      greater copy number of the target sequence. Real-time PCR assays are easy-to-use,
      producing results faster than conventional PCR systems and reducing contamination
      risks.

PMID- 17172186
TI  - Intravenous neridronate for skeletal damage treatment in patients with multiple
      myeloma.
AB  - Almost 70-80% of the patients with Multiple Myeloma (MM) in advancer phase, of
      the disease show osteolytic lesions and/or pathologic fractures, with or without
      secondary osteoporosis. An accelerated osteoclast-mediated bone absorption is
      believed to be the main cause of bone damage in MM. Osteoclast can be activated
      by a variety of microenvironmental factors. Bisphosphonates (BF) induce the
      apoptosis of osteoclasts and inhibit osteoclastogenesis, thus preventing bone
      absorption. As well as BFs, the so-called second-generation BF (N-BF) may impair
      the activity of osteoclast. Neridronic acid (NER) is a N-BF molecule officially
      registered for the treatment of osteogenesis imperfecta. Nevertheless, NER has
      shown a remarkable efficacy in Paget's disease, postmenopausal osteoporosis and,
      most recently, in androgen deprivation-treated prostatic carcinoma. The primary
      endpoint of this study was to evaluate hip and spine Bone Mineral Density (BMD)
      modifications over the 12-month treatment with NER in a group of patients
      affected by MM with evidence of initial skeletal damage. Secondary endpoints were
      (1) changes of calcium and total Alkaline Phosphatase (tAP) plasma levels during
      treatment with NER and (2) tolerability of 100 mg NER monthly administration for
      12 months. These data suggest that NER, if administered at these doses and
      timing, might allow at least for one year sustained BMD increases in patients.
      NER has been highly tolerated in this study. The almost complete absence of
      adverse effects has prompted us to reduce the time of infusions at the end of the
      study. In conclusion, this study provides the first data on the efficacy and
      safety of NER in patients with MM-induced bone damage. These initial data
      encourage wider phase III trials to clearly assess its efficacy in preventing
      skeletal-related events and its possible anti-neoplastic properties.

PMID- 17172187
TI  - Role of gut microflora and probiotic effects in the irritable bowel syndrome.
AB  - BACKGROUND: Even though the cause of irritable bowel sindrome (IBS) is not yet
      known, alterations of the intestinal microflora may be important in its
      pathogenesis. AIM: To evaluate the efficacy of rifaximine alone or in association
      with the probiotic strain of Bifidobacterium longum W11 in reducing symptoms in
      patients with IBS. METHODS: We performed a monocentric, prospective, randomized
      open trial including 70 patients randomized in to two groups: Group A (41
      patients) receiving rifaximin 200 (2 cp bid for ten days in a month) followed by
      a formulation of the probiotic strain of Bifidobacterium longum W11(one
      granulated suspension for 6 days on alternate weeks ) and Group B (29 patients)
      receiving only rifaximin 200 (2 cp bid for ten days in a month). The clinical
      evaluation was performed at admission and after 2-months, taking into account the
      method of visual analogous. RESULTS: At the 2-month follow-up, Group A patients
      reported a greater improvement of symptoms compared to patients in group B (p =
      0.010) even if the physician's opinion at T1 did not confirm these results (p =
      0.07). CONCLUSION: The increased colonisation by Bifi-dobacterium longum W11,
      after the cyclic administration of rifaximin, which eradicates the bacterial
      overgrowth of the small intestine, may reduce symptoms, especially those related
      to bowel habit and stool frequency in patients with IBS. The abnormalities
      observed in the colonic flora of IBS suggest, in fact, that a probiotic approach
      will ultimately be justified.

PMID- 17172188
TI  - A randomized trial comparing laryngeal mask airway to endotracheal tube in
      children undergoing upper gastrointestinal endoscopy.
AB  - Although the efficacy of laryngeal mask airway (LMA) has been demonstrated for
      securing patency of the airway in children, it has not yet been compared to
      endotracheal tube (ET) in this population. This study aimed to compare the safety
      and efficacy of LMA vs. ET in children undergoing elective diagnostic upper
      gastrointestinal endoscopies. Sixty ASA I-III patients were randomly allocated to
      ET (Group I) or LMA (Group II). A set of cardiovascular and respiratory
      parameters were obtained before, during and after the endoscopic procedure. The
      recovery time and the time to discharge were also registered. The cardiovascular
      and respiratory parameters evaluated in the study varied across the different
      evaluation periods. However, they remained within physiological ranges and were
      not different between groups. The median (range) recovery time was 4 (2-10) min
      and the time to discharge was 58 (36-88) min in the ET group and 3 (1-7) min and
      50 (35-67) min in the LMA group (P > 0.10), respectively. In a 16 month-old, 80
      cm and 10 kg girl, we failed to secure the patency of the airway with LMA. In
      conclusion, the LMA was as effective and safe as ET for securing the airway of
      children undergoing diagnostic upper endoscopies. However, the 3% failure rate
      occurred with LMA.

PMID- 17172189
TI  - Infliximab treatment in psoriatic arthritis: our experience.
AB  - The aim of this work was to give clinical practice recommendations on the use of
      tumour necrosis factor blocking agents in psoriatic arthritis, underlining the
      pathogenetic mechanism of this condition and its articular and dermatologic
      manifestations. We retrace the stages leading to the therapeutic indications of
      biological agents that are presently used in the treatment of psoriatic
      arthritis: Entanercept, Adalimumab, Infliximab. We also report our personal
      experience describing an emblematic case of a patient with psoriatic arthritis in
      which a decisive regression of joint/skin involvement was obtained with
      Infliximab treatment.

PMID- 17172190
TI  - A case report of visceral leishmaniasis in the Tharaka District, Kenya.
AB  - Leishmaniasis is a parasitic disease that is transmitted through a bite of some
      species of sandflies. It is caused by obliged intra-cellular protozoa of the
      genus Leishmania and is responsible for a broad spectrum of clinical syndromes:
      cutaneous leishmaniasis (CL), visceral leishmaniasis (VL) and mucocutaneous
      leishmaniasis (ML). The visceral disease (classically known as "kala azar") is
      the most aggressive form and if undervalued is fatal. Here we describe the first
      case of visceral leishmaniasis in the Tharaka District reported in literature.

PMID- 17172191
TI  - Stercorary aseptic peritonitis due to diastatic caecal perforation: computed
      tomography findings.
AB  - Caecal perforation is a complication secondary to colon obstruction. It may
      present with insidious clinical features and may be associated with chronic
      constipation. The event may become severe due to the peritonitic development. We
      present a case of caecal perforation associated with sub-occlusive carcinoma of
      the left colon and hypotonic colitis caused by chronic lavative abuse,
      demonstrated with Computed Tomography.

PMID- 17172192
TI  - Bone necrosis of the jaws associated with bisphosphonate treatment: a report of
      twenty-nine cases.
AB  - Bone necrosis of the jaws is often related to head and neck radiotherapy, to
      surgical procedures at maxillary or mandibular level but also to various local
      and systemic factors such as haematological diseases, haemoglobinopathies and
      systemic lupus eritematosus; its pathogenesis maybe associated with defects of
      vascularization. Bisphosphonate are synthetic analogues of pyrophosphate used for
      the treatment of hypercalcemia in patients with malignancies and bone metastasis
      and for the treatment of many other disorders such as metabolic bone diseases,
      Paget's disease, and osteoporosis; their pharmacological activity is related to
      the inhibition of the osteoclastic function which leads to resorption and
      reduction of bone vascularization. Since the end of 2003 Bisphosphonate
      associated Osteonecrosis (BON) has become an increasing problem and the test of
      that is the increase of the relative published case report and case series. Here
      we report 29 cases of bone necrosis of the jaws in patients treated with
      pamidronate (Aredia), zoledronate (Zometa) and alendronate: 15 underwent surgical
      procedures and 14 occurred spontaneously. Among these patients (21 females, 8
      males; mean age between 45 and 83 years); 14 were treated for bone metastasis, 12
      for multiple myeloma and 3 for osteoporosis. Bone necrosis involved only maxilla
      in 7 patients, only mandible in 20 patients and both in 2 patients. Six patients
      had multiple osteonecrotic lesions, 3 contemporary lesions and 3 non
      contemporary. In these patients we performed 3 kinds of therapy, associated or
      not: medical therapy (with antibiotic drugs, antimycotics and antiseptic
      mouthwashes), surgical therapy with curettage or sequestrectomy and Nd:YAG laser
      biostimulation.

PMID- 17172193
TI  - Diet and cancer.
AB  - The aim of our study is to evaluate the relationship between diet and cancer
      development. It has been estimated that 30-40% of all kinds of cancer can be
      prevented with a healthy lifestyle and dietary measures. A low use of fibres, the
      intake of red meat and an imbalance of Omega-3 and Omega-6 fats may contribute to
      increase the risk of cancer. On the other hand, the assumption of lots of fruit
      and vegetables may lower the risk of cancer. Protective elements in a cancer
      preventive diet include selenium, folic acid, vitamin B12, vitamin D, chlorophyll
      and antioxidants such as carotenoids (alpha-carotene, beta-carotene, lycopene,
      lutein, cryptoxanthin). Ascorbic acid has limited benefits if taken orally, but
      it effective through intravenous injection. A supplementary use of oral digestive
      enzymes and probiotics is also an anticancer dietary measure. A diet drawn up
      according to the proposed guidelines could decrease the incidence of breast,
      colon-rectal, prostate and bronchogenic cancer.

PMID- 17172195
TI  - Moving toward a global perspective of school nursing.

PMID- 17172194
TI  - [Diagnosis and treatment of tobacco dependence].

PMID- 17172196
TI  - Implementing and evaluating the National Healthy School Program in England.
AB  - The purpose of this article is to trace development of the National Healthy
      School Program (NHSP) from a global concept to implementation at the local school
      level in England with a view toward clarifying and, more importantly, determining
      if implementation is proceeding as planned, as evidenced by the presence of
      process evaluation. The NHSP is designed to serve as a catalyst for health
      promotion in schools by identifying core health themes linked to evaluation
      principles in the whole-school approach. In this analysis, process evaluation of
      the NHSP whole-school approach indicates that program data are collected and
      recorded, but these data are not used to form an evidence-based program
      implementation strategy to transform the data into action. The NHSP brings
      valuable concepts to the global school health community that should be embraced
      because schools are increasingly being recognized as key settings for health
      promotion activities.

PMID- 17172197
TI  - Advocating for a harm-minimization approach to drug education in Australian
      schools.
AB  - The concept of using a harm-minimization approach to drug education in Australian
      schools has existed in both national and state government policy documents for
      over two decades. However, this approach appears to be ineffectively and
      inconsistently incorporated within the curriculum. Harm minimization emphasizes
      strategies that reduce the harms associated with drug use and prevent related
      health and social problems. Traditional drug education programs that promote
      abstinence as the only option may not be realistic and appear to have had limited
      success. School nurses in the state of Victoria have a significant role in
      improving both the understanding and adoption of this approach through advocacy,
      education, and their understanding of evidence-based practice.

PMID- 17172198
TI  - Conversion of school nurse policy and procedure manual to electronic format.
AB  - Policy and procedure manuals are essential to establishing standards of practice
      and ensuring quality of care to students and families. The Olathe District
      Schools (Kansas) Technology Department created the Virtual File Cabinet to
      provide online access to employee policies, school board policies, forms, and
      other documents. A task force of school nurses was formed to convert the nursing
      department's policies, procedures, protocols, and forms from hard copy to
      electronic format and make them available on the district's Virtual File Cabinet.
      Having the policy and procedure manuals in electronic format allows for quick
      access and ease in updating information, thereby guaranteeing the school nurses
      have access to the most current information. Cost savings were realized by
      reducing the amount of paper and staff time needed to copy, collate, and assemble
      materials.

PMID- 17172199
TI  - Acceptability of a school-based intervention for the prevention of adolescent
      obesity.
AB  - This article describes the development and pilot testing of a computer-based,
      multiple-behavior obesity prevention program for adolescents. Using the
      Transtheoretical Model as a framework, this intervention offers individualized
      feedback based on readiness to engage in physical activity, to consume fruits and
      vegetables, and to limit television viewing. Focus groups and interviews with
      students, teachers, school administrators, and experts guided the development.
      Forty-five students participated in a baseline intervention session and completed
      a 16-item acceptability measure. Ratings were positive, with item means ranging
      from 3.60-4.75 on a 5-point scale. Student responses to open-ended questions
      aided in the enhancement of the intervention, for which an effectiveness trial
      begins in September 2006. This formative work demonstrated the acceptability of
      this school-based intervention approach, which can be promoted and prescribed by
      school nurses. Further, if found effective, it can be disseminated as an
      efficient, low-cost, population-based approach designed to address the epidemic
      of obesity.

PMID- 17172200
TI  - Gender differences in extrafamilial sexual abuse experiences among young teens.
AB  - Extrafamilial sexual abuse experiences of young adolescents (ages 10-14),
      particularly young teen boys, are not well studied. This retrospective chart
      review study compared psychosocial correlates and victimization experiences
      between young adolescent girls (n = 226) and boys (n = 64) referred to a hospital
      child advocacy center. Several differences in risk behaviors and abuse
      experiences were found: Girls were more likely to have run away, to be truant
      from school, to report substance use, to have multiple perpetrators, and to have
      physical findings from the abuse. Boys were more likely to have a diagnosis of
      attention deficit disorder and to report anal penetration, and rarely disclosed
      abuse at the time of the incident. Peers were girls' most common choice for
      disclosing abuse, whereas boys confided most often in their mothers or other
      adults. These findings suggest sexually abused young adolescent girls and boys
      need distinct, developmentally appropriate screening and care in school and
      health care settings.

PMID- 17172201
TI  - Sex parties: female teen sexual experimentation.
AB  - Adolescent participants in a study aimed at exploring the nature and
      characteristics of girls' dating relationships revealed the phenomenon of sex
      parties. These teens defined a sex party as an opportunity to engage in sexual
      contact outside of typical dating relationships. Sexual activity could involve
      actual intercourse, but usually involved sex acts without vaginal intercourse.
      Data were collected through 22 semistructured interviews with female adolescents,
      ages 15-18. All the participants knew of sex parties, however, only a subgroup of
      these adolescents actually participated in activities loosely defined by teens as
      sex parties. Alcohol was common at these parties, but female teens asserted that
      they consumed alcohol willingly to relax, as opposed to being coerced to do so.
      Some teens expressed regret following participation in a sex party, although none
      reported sexual coercion or abuse.

PMID- 17172202
TI  - Young people, pornography, and sexuality: sources and attitudes.
AB  - The purpose of this study was to investigate the use of and attitudes among young
      people toward pornography and their sources of information about sexuality. Eight
      hundred and seventy-six young people ages 15-25 years (555 females and 321 males)
      who visited a youth center in Sweden for a period of 1 year answered a
      questionnaire about their use of pornography, their attitudes toward pornography,
      and sources of information about sexuality. Although most had seen pornographic
      movies, the youngest boys reported viewing the most pornography. The male
      participants reported that the most common reason they viewed pornography was to
      get aroused and to masturbate, whereas the female participants stated that they
      viewed pornography out of curiosity. The most frequent source of information
      about sexuality was peers. These results illustrate the importance of sex
      education to give factual information about sexuality and to counteract the
      messages about sexuality presented in pornography.

PMID- 17172203
TI  - Influence of the organic compounds on the ecotoxicity in the treatment of foundry
      sludge and olive mill waste.
AB  - The study of the ecotoxicity in two industrial waste materials and the
      relationships with the organic parameters has been conducted. Foundry sludge and
      olive mill waste have been used as industrial waste materials with organic or
      mixed character. Stabilisation/solidification (S/S) and advanced oxidation (AOP)
      processes have been carried out in order to treat both foundry sludge and olive
      mill waste. Analysis of ecotoxicity, total organic carbon, COD and phenol index
      have been evaluated in the untreated waste and end-products. The results of the
      treated samples allow obtaining the best formulations in both processes. The best
      formulations in the immobilisation process have been obtained with Portland
      cement and black carbon, activated carbon or foundry sand ashes. In the AOP
      process, ozone concentrations above 35 mg/l and reaction times equal to 120
      minutes have been the optimal variables. The relationships between the organic
      parameters and the ecotoxicity of the samples have been studied in this paper.
      Furthermore, the global organic parameters have been studied in relation to the
      phenolic compounds. Lineal and logarithmic expressions have been obtained between
      the total organic carbon and phenol index and the ecotoxicity of the samples
      related to the organic parameters, respectively. Ecotoxicity of the samples with
      Vibrio fischeri is recommended as a very promising biotest for the study of the
      characterisation and the evaluation of the treatment of organic and mixed
      character waste and total organic carbon is recommended as global organic
      parameter in the treatment of foundry sludge.

PMID- 17172204
TI  - Measurement of the concentration of radon gas in the Toirano's caves (Liguria).
AB  - The radioactive gas radon, intermediate term of the decay series of uranium and
      thorium, is the main contamination source of underground places and may be a risk
      for high concentration and long exposure time. European and Italian law requires
      radon concentration to be measured in workplaces and, if the "action level" of
      500 Bq/m3 is reached, proper actions must be made in order to decrease the dose
      commitment. Considering natural showcaves or artificial cavities open to public,
      the exposition of the visitors is frequently small, due to the short residence
      time, but accompanying people, remaining underground for long time, may be
      subject to appreciable dose and the radon concentration should therefore be
      monitored. The high humidity in natural caves may impair the use of some
      measuring devices. Therefore, different detection methods were compared (ZnS
      scintillation counters, E-PERM electret ionisation chambers, cellulose nitrate
      alpha-track dosimeters) to select the best procedure for long-term investigation.
      The LR-115 (Kodak) alpha-track dosimeters were insensitive to humidity and
      permitted to monitor a great number of places at the same time. Measurements have
      been carried out in the speleological and archaeological site of the Toirano's
      Caves (Savona, Liguria, Italy) and several points were monitored for two years.
      Radon concentration strongly depends on the site and changes during the year, due
      to the difference between internal and external temperature. The maximum dose
      commitment during the visitors tour, considering the average yearly value of
      radon concentration, was found to be between 1.5 and 4 microSv. It was found that
      no risk exists for visitors, but the evaluation of the dose absorbed by the
      guides and their classification according to the radiation protection law
      requires a complete monitoring of the average yearly concentration of radon and
      of the total time spent by each worker into the cave.

PMID- 17172205
TI  - Thin lead sheets in the decorative features in Pavia Charterhouse.
AB  - The facade of the church of the Pavia Charterhouse, built at the end of the 15th
      century, shows outstanding decorative features made of different stone materials,
      such as marbles, breccias and sandstones. Magnificent ornamental elements are
      made of thin lead sheets, and some marble slabs are inlaid with them. Metal
      elements are shaped in complex geometric and phytomorphic design, to form a Greek
      fret in black contrasting with the white Carrara marble. Lead pins were fixed to
      the back of the thin lead sheets with the aim of attaching the metal elements to
      the marble; in so doing the pins and the lead sheets constitute a single piece of
      metal. In some areas, lead elements have been lost, and they have been
      substituted with a black plaster, matching the colour of the metal. To the
      authors' knowledge, this kind of decorative technique is rare, and confirms the
      refinement of Renaissance Lombard architecture. This work reports on the results
      of an extensive survey of the white, orange and yellowish layers, which are
      present on the external surface of the lead. The thin lead sheets have been
      characterized and their state of conservation has been studied with the aid of
      Optical Microscopy, SEM-EDS, FTIR and Raman analyses. Lead sulphate, lead
      carbonates and oxides have been identified as decay products.

PMID- 17172207
TI  - Non equilibrium thermodynamics and the city: a new approach to urban studies.
AB  - A city can be conceived as a complex self-adaptive system. The multiple
      interactions among its structural elements and dynamic agents, its organization
      on multiple time-space scales, its exchanges with the external context, its
      irreversible dynamics, are signs of complexity. Some concepts from the
      evolutionary thermodynamics, such us the theory of dissipative structures, could
      be extended to the city in order to investigate its behaviour. This theoretical
      framework suggests to analyze the city in terms of entropy and negentropy
      production. An emergy analysis (spelled with an "m") of an urban region is
      presented in order to investigate how cities maintain their organization (and
      decrease their entropy) by virtue of constant energy inflows from the external
      environment. As a result, a non-homogeneous spatial pattern of emergy density is
      shown as an attempt to investigate the multiple relations and energy exchanges
      that take place in an urban region. This approach to urban studies introduces a
      new energy-based vision to understand cities.

PMID- 17172206
TI  - Identification of genotoxic compounds in the airborne particulate matter endowed
      by small aerodynamic diameter in the city of Catania (Italy).
AB  - Airborne particulate matter (PM) is one of the most important polluting factors
      in the atmosphere containing solid particles generated during the combustion
      processes. PM, due to the particle size, is easily inhaled and constitutes a
      potential hazard for the human health. We previously documented, using in vitro
      cell culture systems, cytogenetic damages caused by exposure to a non
      fractionated PM in two different areas from the city of Catania (Sicily, Italy).
      In the present work, the PM was fractionated in six different sub-fractions, and
      the relative extractable organic matters (EOM) were analyzed in order to quantify
      the presence of Polycyclic Aromatic Hydrocarbons (PHAs), a well known class of
      genotoxic agents. More than 70% of the total EOM was found in the PM with
      aerodynamic diameters less than 3.5 microm (PM35), and about 60% of the total EOM
      was detected between PM0.14 and PM1.2. Also the large amount of all the analyzed
      PAHs were found between the PM0.14 and PM1.2. The obtained data indicates that
      the genotoxic effect previously shown on mammalian cells (Chinese hamster
      epithelial liver cells) should be due, in the large part, to the PM with smaller
      particle size, namely less than PM1.2.

PMID- 17172208
TI  - Multidimensional gas chromatographic determination of paraffins, olefins and
      aromatics in naphthas.
AB  - In order to cope with the increasing demand for gasoline and the need to reduce
      environmental impact for sustainable development, refineries have installed
      refining technology by introducing cracking, reforming, isomerization and
      alkylation. The standard EN 228: 2004 outlines the specification that gasoline,
      deriving from the blend of several fractions, must have for use in modem piston
      engines. Naphtha is one of the products from distilling crude oil that can be
      used as starting material in the reforming process whose derivatives, which are a
      fraction of gasoline, depend on the composition of the naphtha. Knowledge of the
      naphtha composition thus enables to provide the final composition of the products
      of reforming, the efficiency of the plant and also provides information about the
      crude oil used. In this paper some naphtha samples were analysed by
      multidimensional gas chromatography. This technique allows in a single analysis a
      good separation of the hydrocarbon types and within each hydrocarbon type a good
      carbon number separation.

PMID- 17172209
TI  - Methodology and application of gc-ms to study altered organic binding media from
      objects of the Kunsthistorisches Museum, Vienna.
AB  - Within the Kunsthistorisches Museum (KHM), Vienna, three off-line GC-MS
      analytical procedures for the identification of natural organic media have been
      refined, tested, and validated on a series of reference materials (partly
      artificially aged) to apply this knowledge for investigations of original,
      historic works of art from the museum's collections. At first, a set of
      artificially aged mockups has been prepared and a reference database has been
      built up for the identification of drying oils, resins, waxes, proteins and
      polysaccharides. Some interesting observations concerning the alteration of the
      composition of these organic media during different ageing steps are presented in
      the following text. In addition, some selected examples for the application of
      the refined techniques for the analysis of real samples from various museum
      objects are shown.

PMID- 17172210
TI  - Determination of environmental persistence and thermogravimetric analysis of
      paper artificially aged by photoirradiation.
AB  - Fabriano paper was aged by irradiation with ultraviolet light (k=310) in a
      veterometer for 300 hours. At fixed time intervals, samples of the paper under
      test were analysed by titanium dioxide photosensor to determine electrochemically
      the "environmental persistence" index, by a suitable conductimeter method, to
      determine the specific conductivity variation and by thermogravimetry to
      determine the moisture content, the onset temperature of the cellulose
      degradation process and the value of the activation energy of the same process.
      The behaviour of these different types of indicators displayed approximately
      monotonous trends as a function of time.

PMID- 17172211
TI  - Classification and technology of byzantine mosaic glass.
AB  - Glass-making is a very sophisticated skill and the contribution given by the
      chemical analyses of glass materials is fundamental for the classification of
      glass types and for identifying compositional groups according to consistent
      characteristics that can be associated with chronological and geographical
      differentiations. The chemical composition of glasses is particularly complex: to
      a few basic constituents many components were added, either derived from
      impurities in the raw materials or intentionally incorporated into the glass mix.
      The field of study concerning the chemical composition and the technology of
      Byzantine mosaic production has not been dealt with in a systematic manner and
      certainly not exhaustively from the view point of classification according to the
      reconstruction of chronological and geographical development. Nevertheless, it is
      of great interest because it is probable that during the Byzantine period the
      production of mosaic glass was greater than for any other type of glass. We
      propose a methodology for classifying Byzantine mosaic glasses on the basis of
      simple statistical treatment of the chemical composition data. Compositional data
      relative to basic and accessory constituents together with colorants were
      analysed and elaborated through binary diagrams. Byzantine glasses are also
      compared to glasses of different epoch and provenance.

PMID- 17172212
TI  - Sediment metal contamination in a creek flowing from a pristine to an industrial
      area of Trieste Province (Italy).
AB  - The following metals: Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were determined by
      inductively coupled plasma - atomic emission spectroscopy (ICP-AES) in fluvial
      sediments of Rosandra Creek, using two different, strong and mild sediment
      decomposition methods. The purpose was to obtain information about the
      contamination by metals and distribution paths of pollutants in the area crossed
      by Rosandra Creek: this little river is the unique epigeous watercourse in the
      Italian Karst and very few data can be found in literature. In this area, we can
      find a natural park, but also agricultural activities and an industrial district
      that was recently defined as "polluted site of national interest". By comparing
      the results of the strong and mild extraction we have obtained the percentage of
      extraction and enrichment factors for each metal in the different sediments of
      the sites R2 and R3 exposed to pollution, while the site R1 was considered as a
      pristine one because situated in the natural park. The computed enrichment
      factors are generally not very high, but copper, lead and zinc have factors that
      require attention. The principal component analysis (PCA) shows that the
      typically anthropogenic metals (as Cr, Pb, Cu and Zn) constitute the first
      factor, while the lithogenic metals, as Fe and Ni, constitute the second one;
      moreover the score plots permit to classify and distinguish the 3 sites: site R3,
      possibly the more exposed to contamination, has high scores both for
      anthropogenic and lithogenic metals.

PMID- 17172213
TI  - Chemical and physical analysis for the improvement of the dry mounting method for
      fragile documents.
AB  - Paper lamination is a widely used method to consolidate fragile documents.
      Previous studies have presented a new method of lamination that allows the
      consolidation of documents before undertaking aqueous treatments. In this method
      a thin Japanese paper coated with an acrylic resin is applied on the fragile
      document by means of a heated press. In this work we optimised the preparation of
      the lamination sheets as well as the working procedures, and we were able to
      establish that our laboratory-made specimens are chemically stable, easily
      reversible and permeable to aqueous solutions. The latest property is of
      particular importance, since it allows a subsequent aqueous deacidification even
      for fragile documents. The laminated paper documents were further analysed by
      means of colorimetry and FTIR spectroscopy before and after accelerated ageing as
      well as by determination of the alkali reserve left on the coated paper, in order
      to compare our lamination method with other commercially available lamination
      sheets.

PMID- 17172215
TI  - [Inaugural Speech].

PMID- 17172214
TI  - Formaldehyde activity on historical glass objects in museum microclimate.
AB  - Degradation of some cultural heritage monuments has been caused by interaction
      with the closest environment (micro-climate). Amount of separate compounds is
      very small and because of it, this fact becomes neglected. Time and temperature
      can induce their activity finally causing deterioration. In this category organic
      compounds can be interpreted as one of museum show - case element. This statement
      has been improved by testing glass objects and their suitable sensors (model
      glasses). Destructive activity of formaldehyde on historical glasses belonging to
      the XVIII-th c. objects with totally different compositions has been confirmed by
      carried out experiments. For historical material which is very limited, sensor
      glass method has been applied. Sensors are prepared on the base of results of
      chemical analyses of original glass chemical analyses and melted on laboratory
      scale (according to historical data). Induced corrosion for sensor supports
      knowledge about deterioration process in real micro-environmental conditions. The
      following testing methods were used: scanning electron microscopy (SEM), energy
      dispersive spectroscopy (EDS), optical interferometer (OI), inductively couple
      plasma (ICP).

PMID- 17172216
TI  - [Cardiac transplant and artificial heart. Historical data].
AB  - After mentioning the importance of implementing these techniques, frecuently used
      both in USA and Spain, he refers to his experience on 70 dogs since the end of
      the 50's in the last century. Not only does he refer to the heterotopic
      transplant, on the neck, undertaken to test the importance of the denervation,
      maintenance of the viability of the organ using hypothermia, and the
      anatomopathologic study of the inmunologic rejection, but also to the orthotopic
      transplant, this is the replacement of one heart by other, using extracorporeal
      circulation. He refers to the first transplant practiced by Hardy, on the 23rd of
      January 1964, in which he unsuccessfully used the heart of a chimpanzee and to
      the one performed by Barnard the 3rd of December 1967, with a survival span of 18
      days. He mentions current techniques to preserve the replacement heart, using
      POPS, as well as the procedures to avoid the rejection and the clinical
      experience in Spain until now, including the obtained results. Thereafter, he
      makes a detailed description of the Liotta's artificial heart, the Jarvik 7
      (Symbyon, CardioWest), which provided a survival period of 112 days. Also he
      refers to the Jarvik 2000, the model of DeBakey, the Novacor, the AbioCor,
      explaining the experience achieved with them, ending with the description with
      the model proposed by Schenk, in Cleveland, the MagScrew TAH.

PMID- 17172217
TI  - [Commemoration of the 25th anniversary of the Health Research Foundation].

PMID- 17172218
TI  - [Demographic changes and health management].
AB  - Since our Constitution declaration in 1978 and General Law for Health in 1986, to
      date, the Spanish society has undergorne marked social changes. Socio-economic
      and health indicators in Spain have also improved as to an increased life
      expectancy, important reduction in infant mortality, and favourable changes
      reported in the national Health Survey. Risk factors influence the main causes of
      death, thus it is said that "man does not die but it kills himself". Healthy
      health practices are specified, and there is empirical evidence of greater
      disability-adjusted life years, a better adherence to Mediterranean diet, no
      smoking, moderate consumption of alcohol, enough time of sleeping, weight
      control, avoiding obsity and overweight, and increased physical activity, all the
      above practices achieving a healthier life. At a global scale in the world we
      live, famine has no frontiers, and fighting against this plague can not await
      longer. Overall, health and poverty are correlated and it must be overcome for
      reasons of human dignity, universal rights (even in ius gentium), and ethical
      dimension as normative of new socio-economic structures. Present must be
      transformed to recover hope in ou global world, still hungry, and in need of
      justice, enlightenment and solidarity.

PMID- 17172219
TI  - [Strategies of vaccination for adult population in Spain in the actuality].
AB  - The introduction of vaccines around the world has avoided millions of deaths
      among children and adults every year. Taking into account that some vaccines
      administered in the childhood do not lend long term immunity, unless a booster
      dose is given, vaccinated subjects return susceptible with the course of time.
      Implementation of vaccination policies and recommendations to adult population is
      important in order to complement vaccination childhood programs and intensify its
      impact in the infection control.

PMID- 17172220
TI  - [Infant feeding and future of manking. Human milk. Human milk banking].
AB  - Infant feeding and future of mankind. Human milk. Human milk banking. Human milk
      is the specific food for infants, it is essencial for suitable growth and
      development and it spreads its influence until adult life and later. The
      advantages of breastfeeding for infants and mothers are unquestionable. In the
      seventies WHO registered a significant decrease of breast feeding that was
      recovering from the eighties in our country. Nowadays, the maternal intention of
      breastfeeding is high, but the total duration of the breast feeding is too short.
      To promote breastfeeding is urgent, specially its duration along infancy. When an
      infant can't be fed with milk of his own mother, pasteurised milk of selected
      donor mothers is the best option specially for high risk or ill infants. This
      milk is got, managed and distributed by human milk banks. We have not human milk
      banks in Spain, even though we had them in the recent past. Hence it is very
      important to stablish human milk banking in our country for giving human milk to
      prematures and ill neonates and infants.

PMID- 17172221
TI  - [Monogenic forms of diabetes mellitus].
AB  - Through the years the evolution of the concepts in the different classifications
      of Diabetes Mellitus keep a close relationship with the advance of the scientific
      knowledge of this matter. In this way the last classification adopted in 1995 by
      the American Association of Diabetes and the World Health Organization has an
      etiologic basis, but in some aspects is already obsolete. With the new knowledges
      this classification should be modified including a group dedicated to monogenic
      diabetes. In this group should be considered diabetes MODY 1 to 6, constituted by
      the forms expressed by mutations of transcription factors and the glucokinase
      enzyme. There are other patients named MODY X, because the responsible genes of
      the diseases have not been identified yet. Also in this section might be included
      the mutations of the Kir6.2 subunit of the K+ channel recently described in the
      beta cell. It is possible that in a near future other forms will be described,
      which will contribute to a better understanding of the monogenic diabetes.

PMID- 17172222
TI  - [Stress and inflammatory bowell disease (I.B.D). Therapeutic strategies].
AB  - Clinical and animal studies indicate that stress can contribute to the onset
      and/or the worsening of the course of inflammatory bowel diseases (IBD). In a
      model (inmobilisation stress for 6 h.) in rats it has been demonstrated that
      stress increases colonic inflammatory damage, as well as antiinflammatory
      prostaglandins and of the nuclear receptor PPARgamma. This inflammation is
      followed by an increase in the permeability of the colonic mucosa barrier and a
      decrease in IgA levels. All these parameters contribute to the bacterial
      traslocation to other organs. PPARgamma agonists drugs prevent these inflammatory
      changes as well as the disfunction of the mucosal colonic barrier, which suggests
      its use in the worsening episodes of IBD produced by stress.

PMID- 17172223
TI  - [Erectile dysfunction, physiologic approach, diagnosis and therapy].
AB  - Erectile dysfunction is defined as the consistent or recurrent inability to
      obtain and/or maintain a penile erection sufficient for sexual activity. Erection
      is a vascular phenomenon under a psychoneurological control and situated in an
      hormonal environment. A variety of treatment options are available to the
      clinician including medical, psychological and surgical treatments. The choice of
      therapy should be based on careful matching of the patient's needs and
      preferences with the available treatment options.

PMID- 17172224
TI  - [Detection of prostate cancer: yes or no?].

PMID- 17172225
TI  - [Medical folder of Bela Bartok].

PMID- 17172226
TI  - [Network "interactome"].

PMID- 17172227
TI  - [New insights into the etiopathogenesis of atherosclerosis and atherothrombosis].
AB  - The composition of an atherosclerotic plaque is an important determinant of
      plaque stability. Unstable rupture-prone plaques are characterized by a thin
      fibrous cap that contains few muscle cells. Several lines of evidence suggest
      that macrophage activation in the unstable shoulder of the plaque could
      contribute to plaque rupture by releasing toxic factors, possibly nitric oxide
      (NO), to smooth muscle cells. These macrophages are also involved in the uptake
      of apoptotic cells (AC) and the inefficient removal of the latter might
      contribute to the formation of the necrotic core through accumulation of necrotic
      debris. Furthermore, these AC rapidly expose phosphatidylserine on their surface,
      which is a potent substrate for the generation of thrombin and activation of the
      coagulation cascade. The following new insights in the etiopathogenesis of
      atherothrombosis will be discussed: (1) Human atherosclerotic plaques contain
      amyloid precursor protein (APP) and beta-amyloid peptide, which is cleaved from
      APP and which has been extensively studied in Alzheimer's disease. Macrophages
      phagocytose platelets,which contain APP in their alpha-granules and this platelet
      derived APP is subsequently proteolytically processed in these macrophages into
      beta-amyloid The latter is involved in the upregulation of the inducible NO
      synthase which results in an increased production of toxic amounts of NO. (2)
      Phagocytosis of the pro-coagulant ACS is severely impaired in advanced human
      atherosclerotic plaques. Several factors present in the atherosclerotic
      lesion,such as accumulation of indigestible material in the macrophage
      cytoplasm,oxidative stress,and the presence of oxidized LDL or oxidized
      erythrocytes may contribute to the impairment of phagocytosis. (3) In order to
      study the impact of the impaired phagocytosis by the macrophages on the
      atherosclerotic lesion development,a double knock-out mouse was created which
      spontaneously develops atherosclerosis combined with a deficient phagocytotic
      capacity. Completely unexpected the double-knock out mouse developed an until now
      not described phenotype resembling the metabolic syndrome including a spectacular
      increase in body weight,accumulation of abdominal fat and fat in the liver and
      increased plasma levels of cholesterol. Furthermore the atherosclerotic lesions
      demonstrated a striking different morphology as compared to the lesions present
      in mice which spontaneously develop atherosclerosis.

PMID- 17172228
TI  - [Clinical and epidemiological study of multiple sclerosis in Volgograd city].
AB  - Descriptive and analytical study of multiple sclerosis (MS) has been first-ever
      carried out in population of Volgograd city, South region of Russian Federation.
      At the period of the study (1996-2000) the population was estimated as 814 100
      adult persons. An average age-adjusted level of MS prevalence was 31.9 per
      100,000, MS incidence--9.8, mortality 1,8. Thus, the city is at a moderate risk
      for MS, however the incidence of the disease appeared to be rather high that
      indicates a further increase of MS patients number in this population. The
      highest level of MS prevalence was registered in two districts with poor
      ecological characteristics and numerous industries: Krasnoarmeysky (52.4 per
      100,000 persons) and Krasnooktiabrsky (46.4). An analytical case-control study
      included data collected from 178 pairs (73.6% female) of MS patients and controls
      matched for age, sex and ethnic origin. Significant differences between patients
      and controls were detected as follows: patients more often had blue eyes as
      compared to dark ones; in the patient group mother's age at birth was above 30
      years; patients more often lived near chemical and/or oil factories at age before
      15 years; they more often reported a presence of stress factors in the family and
      chronic tonsillitis. Association with other factors, including infections,
      nutrition, acute and chronic diseases, poisoning, traumas, family history of
      different diseases, contact with animals etc, has not been found. A possible
      association between environmental factors and features of MS course were
      analyzed. Living near chemical factories at age before 15 was associated with
      more active MS course, i.e. high frequency of progressive course, short period
      from MS onset to confirmed EDSS=3, short duration of first remission. The same,
      though less significant, influence may exert the presence of herpes infection and
      chronic tonsillitis at age under 15.

PMID- 17172229
TI  - [Multiple sclerosis in Eastern Siberia: a 20-year prospective study in
      Novosibirsk city].
AB  - A prospective epidemiological study of multiple sclerosis (MS) has been conducted
      in Novosibirsk with the following analysis of MS prevalence and incidence and
      estimation of the disease frequency in different age groups. The wave-like change
      of MS incidence within 1.5-2.5 per 100,000 persons was observed from 1970 to
      2002, with a trend to decreasing, in particular among men, over the last decade.
      At the same time, there was an increase of MS prevalence (from 29.2 in 1984 to
      54.4 in 2003) combined with increasing of illness duration and a fraction of
      slowly progressive MS variants.

PMID- 17172230
TI  - [Multiple sclerosis in ethnic groups of Bashkortostan Republic].
AB  - Clinical presentations and course of multiple sclerosis (MS) have been studied in
      ethnic groups of Bashkortostan Republic. An analysis of 4 groups of patients, 234
      Tartars, 80 Bashkirs, 22 Chuvashes and 237 Russians, revealed that the prevalence
      of MS was the least in the Bashkirs--3 times less than in Tartars (chi2 = 7.84; p
      < 0.05) and 2 times less than in Russians (chi2 = 2.95; p < 0.05). In all the
      groups, the disease more often developed in women. Mean age at disease onset in
      women was less in Tartars and Chuvashes and by 1 year more in Bashkirs. In debut,
      polysymptomatic beginning and movement disorders prevailed in patients with
      different ethnic origin. The higher prevalence of MS in Tartars, Russians and
      Chuvashes as compared to Bashkirs is probably caused by historically developed
      isolation of populations in the territory of the republic and by the features of
      marriage traditions.

PMID- 17172231
TI  - [Epidemiology of multiple sclerosis in Tiumen' region].
AB  - Prevalence of multiple sclerosis (MS) was evaluated in the pilot study of 731
      patients living in Tyumen city and a southern part of Tyumen region as well as in
      Khanty-Mansi (KMAO) and Yamal-Nenets (YNAO) autonomic okrugs. An index of MS
      prevalence was 22,4 per 100,000 in Tyumen region as a whole. This index was
      higher--29.1 per 100 000 - in the southern part. In KMAO and YNAO, the MS
      prevalence was 14,3 and 27,8 respectively. Women prevailed among patients in all
      the regions, their number being twice higher (461 and 270). However, if in the
      southern part and in KMAO this ratio was approximately equal, in YNAO percentage
      of men was significantly higher. It should be noted that these data need further
      study. We revealed that using of current diagnostic criteria may often lead to
      misunderstanding of diagnosis of "definite" MS. Essential difference in MS
      prevalence in different regions may be explained by ethnical stratification. In
      particular, there are many newly migrated people in the okrugs and MS occurs more
      often in that group. At the same time, there is no any information on the
      prevalence of "definite" MS among the native-born population of KMAO and YNAO.

PMID- 17172232
TI  - [Oxidant stress in the pathogenesis of multiple sclerosis].
AB  - The problem of pathogenesis of multiple sclerosis is of great importance in
      modern neurology and its solution allows to determine a pathogenetic approach to
      treatment of this severe disease. Parameters of intensification of lipid
      peroxidation and indices of the state of enzymatic and non-enzymatic patterns in
      antioxidant defense system in different clinical forms and at different stages of
      MS course have been analyzed. The data obtained confirm the presence of oxidant
      stress in the development of pathological process in MS.

PMID- 17172233
TI  - [Clinical significance of adhesive properties of leukocytes and blood serum in
      patients with multiple sclerosis].
AB  - Adhesive blood properties have been studied in 100 MS patients with the help of
      the new method developed on the basis of the leucocyte adherence inhibition (LAI)
      test, which was based on the calculation of the ratio of adhesive cells to non
      adhesive ones. The value obtained was called the Index of Spontaneous Adhesion
      (ISA), while the respective indicator reflecting the effect of adhesion
      strengthening under the influence of autoserum, being expressed by 30% and more,
      was named the Effect of the Adhesion Strengthening (ES-a). Blood samples of 54
      donors and 31 patients with other neurological diseases were used as controls.
      Statistically significant increase of ISA values of MS patients was detected as
      compared to the group of donors. The highest indices of ISA and ES-a were found
      in the primarily progressive course and at the stage of MS exacerbation in the
      remitting course. Correlation between levels of adhesion and clinical features as
      well as parameters of clinical and humoral immunity are described. A role of
      membrane and soluble forms of adhesion molecules in initiation and progression of
      the immunologic process in MS is discussed.

PMID- 17172234
TI  - [The peculiarities of plantar pressure distribution during gait in different
      variants of functional system impairment in patients with multiple sclerosis].
AB  - Gait disturbance is a prominent disabling presentation of multiple sclerosis. The
      data on the distribution of plantar pressure during gait and its relation to the
      level of neurological deficit in various disturbances of pyramidal and cerebral
      functions in remitting type of multiple sclerosis are presented.

PMID- 17172235
TI  - [Structural and functional analysis of the cortico-spinal tract in multiple
      sclerosis].
AB  - The study aimed at comparison of transcranial magnetic stimulation (TMS)
      parameters to MRI data in multiple sclerosis (MS), taking into account clinical
      course of the disease. TMS was conducted in 56 patients and in 10 age- and sex
      matched healthy controls. According to stage of activity and variant of the
      course, the patients were divided into 2 groups: one at the stage of exacerbation
      and another--at the stage of remission with secondary progressive MS. Latency of
      segmental evoked motor response was similar in patients and controls.
      Statistically significant between-group difference or trend toward changing of
      some TMS parameters were found that indicates a slow-down of the impulse
      conducting along the cortico-spinal tract, which is characteristic of
      demyelinization process. The changes were more pronounced in secondary
      progressive MS. According to MRI data, a square of the spinal cord on the level
      of the intervertebral disk center C2/C3 was significantly smaller in the group of
      patients with secondary progressive MS than in that with exacerbation of the
      disease. The TMS parameters correlated both with the level of the focal
      demyelinization process and with the square of the spinal cord on a level
      selected. It allows to estimate expression of atrophic changes caused, in its
      turn, not only by myelin loss but also by axon loss.

PMID- 17172236
TI  - [Vertebral syndrome in multiple sclerosis: causes, clinical peculiarities and
      problems of differential diagnosis].
AB  - Presented is a review of the literature on the main causes of vertebral syndrome
      in multiple sclerosis (MS): dystrophic processes in spinal motor segments,
      disturbance of spinal static, development of functional blockade, osteoporosis,
      appearance of demyelinization foci in roots and the spinal cord, myelopathy,
      replacing foci by cavities. The authors report the results of clinical and MRI
      study of 115 patients with MS and single out some dissimilarities of vertebral
      syndrome in MS and dystrophic lesion of spinal cord as follows: in MS pain is
      long-term, non-intensive, without distinct periods of deterioration and
      improvement; muscle tonic disturbances are less pronounced but present on the
      level of all spinal compartments; intensity of root disorders is significantly
      less and location of clinical symptoms often does not correspond to the level of
      altered spinal motor segments. The Lermitt symptom and its analogs are described,
      the former being found in 14.7% of patients with remitting course, and their
      relation to the loci in the cervical part of the spinal cord is revealed. It is
      stressed that these loci could lead to an earlier onset of vertebral pain
      syndrome in patients with MS.

PMID- 17172237
TI  - [Risk factors of osteoporosis in women with multiple sclerosis].
AB  - Multiple sclerosis (MS) is a progressive disease that leads to early disability
      of young adults at a reproductive age. Motor disturbances caused by progressive
      pyramidal deficit and cerebellar dysfunction, accompanied by ataxia with frequent
      falls, and early decrease of physical activity are risk factors of osteoporosis
      in MS patients. A relapsing-remitting course of the disease with frequent attacks
      demands multiple courses of steroid therapy. Long-term steroid treatment causes
      bone loss and development of secondary osteoporosis. We have shown that reduced
      bone mineral density (BMD) in lumbar spine and femoral neck is associated with
      high level of EDSS score caused by the combination of moderate pyramidal and
      cerebellar dysfunction. An additional risk factor of osteoporosis in MS patients
      is low body weight. The glucocorticoid therapy does not exert a negative impact
      on BMD in lumbar spine and femoral neck in patients with MS.

PMID- 17172238
TI  - [The possibilities of adaptation of patients with multiple sclerosis: the results
      of clinical and psychological study].
AB  - A complex clinical and psychological examination of three groups of patients with
      stable neurological deficit (113 subjects, 77 men and 76 women, aged from 19 to
      67 years) included those with multiple sclerosis (MS), chronic cerebral vascular
      disorders and chronic dorsopathy with illness duration 5-7 years has been carried
      out. Neuropsychological status and quality of life were assessed using the
      following tests: Medical Outcomes Study Short Form 36 Health Survey (SF-36); the
      method of E.B. Fantalova "Level of Ratio of "Values" to "Availability" in
      Different Life Spheres", Integrative Anxiety Test, Manual for the Constructive
      Thinking Inventory, Coping test (Lazarus), Beck depression scale. In total, 42
      traits on 6 tests have been studied. The study was conducted before and after
      treatment (21 +/- 2 days). The results revealed that patients with chronic
      neurological disorders, in particular with MS, often had subclinical depression,
      which negatively influenced the disease course, and needed treatment. A high
      level of anxiety was found in MS patients that was related to situational social
      defensive reaction. Low ability to positive reevaluation of life situations, one
      of the causes of anxiety states, was observed in all the groups, especially in
      MS. In MS patients, their real state was not consistent with their perception of
      this state. They also were featured by personal superstitious thinking. Most of
      the patients with MS had a good constructive thinking, preserved ability to
      emotional and behavioral self-control that indicated favorable prognosis in
      future complex rehabilitation. After the course of symptomatic vascular and
      metabolic therapy, with the exception of antidepressants and neuroleptics, the
      appearances of depression and anxiety as well as expression of social defensive
      reactions and situational phobic component of anxiety were decreased that
      suggested the necessity of inclusion of individual psychotherapy as a part the
      complex rehabilitation therapy.

PMID- 17172239
TI  - [Vestibular cochlear disturbances in multiple sclerosis].
AB  - To specify the character of vestibular cochlear disturbances in multiple
      sclerosis (MS) and mechanisms of their formation, the objective quantitative
      evaluation of experimental caloric nystagmus using the computer
      electronystagmographic method and a comparison of hearing impairment with
      asymmetry of vestibular reactions were conducted in 48 patients with MS. The
      peculiarities of vestibular disturbance found in the study suggest a predominance
      of central vestibular syndrome with both subtentorial and supratentorial traits.
      The influence of the heat stimulus of vestibular analyzer (hot water caloric
      test) in multiple sclerosis revealed during computer electronystagmography may
      have diagnostic value.

PMID- 17172240
TI  - [Clinical and radiological (PET, MRI) correlations depending on disease
      progression in patients with multiple sclerosis].
AB  - The aim of the study was to investigate the structural-functional changes in the
      cerebral gray matter (cortical and subcortical areas) of patients with multiple
      sclerosis (MS) depending on the disease severity. One hundred and seven patients
      (107) with definite diagnosis of MS (Mc Donald's criteria), aged 16-60 years,
      illness duration 1-30 years, and 21 healthy age-matched controls have been
      studied. Neurological assessment including Kurtzke and EDSS scales (range 0-8)
      was performed in all the patients. The patients and controls underwent MRI with a
      1,5 imager and PET using 18F-flurodeoxyglucose (FDG). A type of the disease
      course was determined as remitting in 63 patients, primarily-progressive in 8,
      remitting progressive in 6 and secondary-progressive in 30. To analyze
      pathogenesis of the disease progression, the patients were divided into 3
      clinical groups: (1) remitting (RRMS, n=63); (2) progressive (PRMS) with EDSS <
      or =6 (n=34); 3) PRMS with EDSS >6 (n=11). Along with the progression of MS from
      RRMS to PRMS and increasing of EDSS, the rCMRglu reduction of the cerebral gray
      matter developed from the supplementary motor cortex of a dominant hemisphere to
      the marked global reduction of cerebral metabolic rate in the PRMS group (EDSS
      >6). In the PRMS group with EDSS56, there was functional reorganization of
      cortical and subcortical areas compensatorily developing with the disease
      progression. In the PRMS group with EDSS >6, the data obtained did not support
      the evidence for the regional compensatory increase of rCMRglu in the same brain
      areas. Decompensation of the functional cortical reorganization in the PRMS group
      with EDSS >6 correlated with diffuse brain atrophy as well as with atrophy of the
      gray matter of the regional basal ganglia, first of all of the thalamus.

PMID- 17172242
TI  - [The design of the protocol for management of patients with multiple sclerosis].

PMID- 17172241
TI  - [Possible mechanisms of chronic fatigue syndrome in multiple sclerosis].
AB  - One of frequent presentations of multiple sclerosis (MS) is chronic fatigue that
      may be determined as a subjective decrease of the physic and/or psychic energy
      level. Fatigue can be divided into asthenia (fatigue in resting state),
      pathological fatigability (exhaustion during physical loading) and fatigue
      concomitant with other symptoms (MS exacerbation). There are central as well as
      peripheral mechanisms of fatigue formation. Frequent is a combination of fatigue
      and affective disorders in MS, in particular depression, as well as sleep
      disturbances (insomnia, restless legs syndrome) that may indicate the common
      origin of their mechanisms, i.e. reduction of serotoninergic and noradrenergic
      systems activity. Endocrinal and autoimmune components are considered as
      important in fatigue syndrome formation, the latter exerting more influence on
      asthenia than on pathological fatigability. Further investigation into
      pathogenetic mechanisms of asthenia (fatigue in resting state), pathological
      fatigability (fatigue in active state) and specification of their differential
      diagnostic features allow not only to understand the essence of this syndrome but
      to choose an adequate individualized therapy.

PMID- 17172243
TI  - [A wide support of patients with multiple sclerosis promotes success of long-term
      therapy].
AB  - The diagnosis of multiple sclerosis (MS) is a life-altering experience that has
      far-reaching and diverse implications for newly diagnosed patients and their
      families. Since the disease is complex and highly variable, it places physical,
      emotional and social challenges on everyone concerned. A number of responsible
      decisions must be made, the most difficult one being the consent to long-term
      therapy. Joint effort of both physicians and patients allow the latter to take up
      properly new life circumstances, get adequate motivation, right and regular
      implementation of the long-term treatment plan aiming to prevent the disease
      progression. The management of many chronic diseases involves medications that
      must be injected on the frequent basis. In MS, such injections can reduce the
      frequency of relapses and slow the disease progression. Pretreatment injection
      self-efficacy expectations, injection anxiety, therapeutic expectations and
      ability to self-inject are significantly related to adherence. Poor patient
      adherence to long-term therapy severely compromises the treatment effectiveness.

PMID- 17172244
TI  - [The results of longitudinal use of copaxone and betaferon in Moscow Multiple
      Sclerosis Center: issues of efficacy and adherence to therapy].
AB  - In last decades, practical neurologists are able to use DMT in multiple sclerosis
      (MS) in every day practice. This paper presents data of 3-year study of DMT
      (copaxone and betaferon) treatment of 280 patients with definite diagnosis of
      multiple sclerosis (MS), 166 patients regularly receiving DMT (104--copaxone and
      62--betaferon) for, at least, 3 years. Clinical symptoms of the patients, reasons
      of treatment withdrawal (48--copaxone and 31--betaferon) and the features of MS
      course after the withdrawal are analyzed. Patients who received betaferon
      previously had more severe MS course with frequent relapses, half of them had
      secondary progressive MS course (SPMS) with relapses. This made impossible a
      direct comparison of the data of two treatment groups. Treatment with copaxone
      reduced 5 times annual relapse rate, from 1.45 before DMT to 0.27 during these 3
      years (p < 0.001), and this reduction remained stable. For 36 months, 40.4% of
      patients were relapse-free though all of them had, at least, one relapse per year
      before the treatment. No EDSS progression was observed in 80% of these patients.
      Treatment with betaferon caused the reduction of relapse rate from 1,84 to 0,69
      per year (2.7 times), 8 patients (26%) with previously active RMS being relapse
      free for 36 months. In 31 patients with SPMS, the reduction of relapse rate was
      also significant, from 1.89 to 0.49 (3.8 times, p < 0.001). Twenty-two patients
      (71%) with previous SPMS did not have EDSS progression for 36 months that
      indicate the positive effect of the therapy. Side-effects were moderate and were
      not the main cause of the treatment withdrawal. The latter was caused mainly by
      clinical un efficacy, most frequently by the increase of EDSS due to
      transformation of the MS course to SPMS without relapses and poor understanding
      by the patient of the goals and the possibilities of DMT. These facts stress the
      significance of improving compliance, motivation and adherence to DMT in everyday
      neurological practice.

PMID- 17172245
TI  - [A comparative analysis of rebif 22-mcg and copaxone efficacy in multiple
      sclerosis].
AB  - A comparative analysis of efficacy and tolerability of such immunomodulating
      compounds as rebif 22-mcg and copaxone used in the treatment of multiple
      sclerosis is presented. The analysis was based on the data obtained in the 2-year
      study of copaxone (145 patients) and rebif 22-mcg (74 patients) therapy carried
      out in the Neurology Institute, Russian Academy of Medical Sciences.

PMID- 17172246
TI  - [Effective treatment of multiple sclerosis with rebif-22 mcg in children and
      adolescences: results of a long-term study].
AB  - Management from an early age and availability of new treatment options have
      changed the outcome of paediatric patients with multiple sclerosis (MS).
      Currently available for treatment of MS in adults, such drugs as interferons beta
      and copolymer-1 are not widely used in paediatric neurological practice. The
      present long-term study of the effect of interferon beta la (rebif-22 mcg)
      included 20 children with MS from Moscow population. The data of this open-label
      study were compared with our previously reported data from the prospective
      population-based study of 67 ethnically-matched children with MS. The results
      revealed early formation of stable neurological deficit at late-onset treatment,
      high therapeutic efficacy when the drug was timely used and good tolerability of
      the treatment. So, it is necessary to use immunomodulating therapy with these
      drugs in children and adolescents as early as possible.

PMID- 17172247
TI  - [The peculiarities of formation and approaches to the treatment of chronic
      fatigue syndrome in young patients with focal brain damage].
AB  - Chronic fatigue (CF) is a syndrome manifesting in cases with focal brain damage.
      It is frequent in multiple sclerosis (MS) and encephalopathies (post-traumatic,
      cerebrovascular, etc). Treatment of this syndrome remains problematic. The study
      aimed to analyze the genesis of CF in patients with different non-active
      neurological diseases with brain damage and possibility of its treatment with the
      complex drug fezam (piracetam plus cinnarizin) in dosage 2 capsules 3 times per
      day. Before the treatment, all the patients had CF, which was directly associated
      with severity of depression in patients with encephalopathies. In MS patients,
      changes in the valuable-and-sense sphere that plays a significant role in human
      behavior and activity underlying self-regulation in critical situations were
      found. Neuropsychological data revealed that in patients with encephalopathies
      psychological and behavioral aspects were more significant in regard with CF
      genesis than in patients with MS. Fesam caused significant decrease of the CF
      severity, which was more prominent in the MS group, while in another group it was
      associated with a decrease of depression severity. Mild side-effects were
      observed in 6 patients (12%) and appeared mainly as sleep disorders. This trial
      allows recommending Fezam for complex treatment of CF syndrome in MS and in
      combination with psychocorrective medicines in cases of encephalopathies.

PMID- 17172248
TI  - [The 1188 A/C ILI2B gene polymorphism in patients with multiple sclerosis and in
      healthy subjects of Tomsk region].
AB  - Multiple sclerosis (MS) is a multifactorial and polygenic disorder of the central
      nervous system, its development being under strong influence of T-helpers type I
      which produce anti-inflammation cytokines. Interleukin 12 (IL12) plays a key role
      in such polarization of the immune response. Genotyping for polymorphism of the
      IL12B gene in the 3'-untranslated region, coding for the p40(IL12B) subunit, has
      been carried out in 62 patients with MS and 129 healthy controls. The C/C
      genotype frequency was twice higher in patients as compared to the controls
      (33.9% and 17.4%, respectively). The allele C in patients was associated with
      shorter duration of the first remission (p = 0.028) which was 1.79 +/- 0.28 in
      those with the C allele and 3.27 +/- 0.68 in other patients. Mean rate of
      relapses per year was also higher (p = 0.079) in patients with the C allele (0.96
      +/- 0.11) comparing with the A allele (0.72 +/- 0.11). During the treatment with
      copaxone, a trend towards increasing of the time before the first relapse was
      observed in patients with the C allele. An analysis of immunologic indices
      revealed that they changed in opposite directions depending on the gene variant.
      The C-allele is suggested to have relation both to liability to MS and to its
      pathogenesis.

PMID- 17172250
TI  - A giant sarcomatoid renal cell carcinoma.

PMID- 17172249
TI  - Utility and direct costs: ankylosing spondylitis compared with rheumatoid
      arthritis.
AB  - OBJECTIVES: To compare utility and disease-specific direct costs between patients
      with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) in
      the Netherlands. METHODS: Patients with AS and those with RA completed questions
      on disease characteristics, the EuroQol-5D (EQ-5D) to assess utility, and
      questionnaire resource utilisation. Resource utilisation was assessed
      prospectively in AS, but retrospectively in RA. True cost estimates (2003) were
      used to calculate the costs. Differences in disease characteristics between AS
      and RA were described, and determinants of EQ-5D utility and costs were explored
      by Cox proportional hazard regressions. RESULTS: 576 patients with RA and 132
      with AS completed the questionnaires. EQ-5D utility (0.63 vs 0.7) was lower, and
      annual direct costs higher in RA (euro5167 vs euro2574). In multivariate Cox
      proportional hazard regressions, there was no difference in utility between the
      diagnostic groups, but patients with RA incurred higher direct costs after
      controlling for age, gender and disease duration. CONCLUSIONS: In patients with
      RA and patients with AS, who are under the care of a rheumatologist, utility is
      equally reduced, but healthcare costs are higher in RA after controlling for age,
      gender and disease duration. These data can be helpful to provide insights into
      the differences and similarities between the healthcare needs of both patient
      groups and to identify issues for further research and for policy in healthcare
      organisations.

PMID- 17172251
TI  - Kidney disease in cardiology.
AB  - This article helps to inaugurate NDT's new section, Kidney Diseases beyond
      Nephrology, by focusing on the convergence of cardiology and nephrology. The
      clinical themes highlighted by the articles chosen for review include cardiac
      screening in renal transplant candidates, cardiac troponins in end-stage renal
      disease patients, contrast nephropathy in coronary angiography and surgical
      coronary revascularization across the spectrum of renal failure.

PMID- 17172253
TI  - Characterization of a large Lebanese family segregating IgA nephropathy.
AB  - BACKGROUND: Familial aggregation of IgA nephropathy (IgAN) suggests that genetic
      factors contribute to the development of this trait. Because clinical
      manifestations in IgAN families are often limited to episodic haematuria, large
      kindreds tractable to linkage analysis have been difficult to identify. METHODS:
      We identified a large Lebanese-Druze kindred ascertained via an index case with
      biopsy-documented IgAN. We performed systematic screening of 38 family members
      and tested linkage to reported IgAN loci. RESULTS: Screening of this family
      identified 16 affected individuals, including 2 individuals with biopsy
      documented IgAN and 14 with chronic renal failure or abnormal urinalyses on at
      least three separate occasions. This kindred spanned five generations and
      contained five consanguineous unions. Multigenerational inheritance suggested
      that autosomal dominant inheritance was most likely. Phenotypic manifestations
      among affected individuals varied from isolated haematuria to advanced renal
      failure necessitating transplantation; one instance of IgAN recurrence after
      transplantation was also documented. Older age was associated with greater
      severity of disease and higher incidence of renal failure. Parametric and non
      parametric analyses with 33 microsatellite markers did not reveal any evidence of
      linkage to reported IgAN loci on chromosomes 6q22-23, 2q36 and 4q22-31.
      CONCLUSIONS: We describe one of the largest multigenerational IgAN kindreds
      reported to date. The high incidence of renal failure among older generations
      suggests a significant risk of progression to renal failure. We found no evidence
      of linkage to known loci, suggesting that familial IgAN encompasses multiple
      subtypes that will require distinction based on genetic or biomarker data.

PMID- 17172252
TI  - The association between recipient alcohol dependency and long-term graft and
      recipient survival.
AB  - BACKGROUND: The causative role of alcohol consumption in renal disease is
      controversial, and its effect on renal graft and recipient survival has not been
      previously studied. METHODS: We analysed the association between pre-transplant
      [at the time of end-stage renal disease (ESRD) onset] alcohol dependency and
      renal graft and recipient survival. The United States Renal Data System (USRDS)
      records of kidney transplant recipients 18 years or older transplanted between 1
      January 1995 and 31 December 2002 were examined. We used Kaplan-Meier analysis
      and Cox regression models adjusted for covariates to analyse the association
      between pre-transplant alcohol dependency and graft and recipient survival.
      RESULTS: In an entire study cohort of 60 523, we identified 425 patients with a
      history of alcohol dependency. Using Cox models, alcohol dependency was found to
      be associated with increased risk of death-censored graft failure [hazard ratio
      (HR) 1.38, P < 0.05] and increased risk of transplant recipient death (HR 1.56, P
      < 0.001). Subgroup analysis demonstrated an association of alcohol-dependency
      with recipient survival and death-censored graft survival in males (but not in
      females), and in both white and non-white racial subgroups. CONCLUSIONS: We
      concluded that alcohol dependency at the time of ESRD onset is a risk factor for
      renal graft failure and recipient death.

PMID- 17172254
TI  - Poor performance of diagnostic tests for atherosclerotic renal artery stenosis-
      discrepancies between stenosis and renal function.

PMID- 17172255
TI  - Alcoholism and homicide with respect to the classification systems of Lesch and
      Cloninger.
AB  - AIMS: Worldwide criminal statistics show a disproportionately high incidence of
      violent offences committed under the influence of alcohol. A psychopathological
      subtyping of alcohol dependence in offenders who committed homicide has mainly
      been related to impulsive and dissocial personalities up to now. METHODS: In an
      investigation on 48 alcohol-dependent offenders who committed homicide, a
      subtyping according to the multidimensional classification systems of Lesch and
      Cloninger has now been conducted for the first time. RESULTS: In Lesch's
      classification, there was a high incidence of homicides committed by type II and
      type III subjects with the comorbidity anxiety and cyclothymia. While type III
      offenders were more often repeat offenders, there was a remarkably high rate of
      first offenders among type II subjects (Chi-squared test; chi(2) = 30.0, df = 3,
      P < 0.001). With respect to Lesch's typology, the blood alcohol concentrations
      did differ significantly in the group of offenders (Kruskal-Wallis, chi(2) =
      18.3, df = 3, P < 0.001), whereas the blood alcohol concentration of type II
      offenders at the time of offence was significantly lower than in type III
      offenders (Mann-Whitney-U, Z = -3.47; P = 0.001). Regarding to the Cloninger's
      typology, no significant differences in the aforementioned parameters could be
      found. DISCUSSION: An excessive noradrenergic reaction of anxiety offenders with
      initial withdrawal is discussed as a possible explanatory model.

PMID- 17172256
TI  - Suppression of symptoms of alcohol dependence and craving using high-dose
      baclofen.
AB  - AIMS: To further test whether the baclofen-induced suppression of motivation to
      consume alcohol in animals could be transposed to humans. METHODS: A patient who
      had neither tolerated nor benefited from other alcohol treatment modalities was
      put on trial with baclofen on a dosage up to 140 mg/day. RESULTS: The patient
      reported dramatic reduction in cravings for and preoccupation with alcohol.
      CONCLUSIONS: High-dose baclofen therapy was associated with complete and
      prolonged suppression of symptoms and consequences of alcohol-dependence.

PMID- 17172257
TI  - Harmful alcohol use in Goa, India, and its associations with violence: a study in
      primary care.
AB  - AIMS: To determine (i) the prevalence and characteristics of harmful alcohol
      consumption in general practice attendees; (ii) social and psychological
      associations with harmful drinking and (iii) recognition of harmful drinking by
      GPs. METHODS: A cross-sectional study of ten general practices in Goa, India. A
      total of 1567 general practice attendees were recruited. RESULTS: A total of 338
      men (41%) and 597 women (81%) reported that they never consumed alcohol. One
      hundred and twenty-eight people or 8.2% scored >or=8 on the AUDIT [123 (15%) men
      and five (0.7%) women] and were classified as harmful or dependent drinkers. The
      population attributable fraction of harmful drinking in the perpetration of any
      physical violence by men over 12 months was 0.36. The population attributable
      fraction of moderate drinking (vs abstention) in the perpetration of any physical
      violence by women over 12 months was 0.27. Doctors identified almost 60% of
      problem drinkers but misidentified approximately 5% of moderate drinkers as
      problem drinkers. CONCLUSIONS: The male pattern of drinking in Goa is one of the
      high rates of abstention coupled with relatively high rates of harmful and
      dependent drinking in those who consume alcohol. Most women are abstainers. These
      data provide the first evidence in India on (i) the role of the GP in
      identification of harmful alcohol use and (ii) the contribution of harmful
      drinking to the perpetration of physical violence from the perspective of the
      alcohol user.

PMID- 17172258
TI  - Knowledge and attitudes about pharmacotherapy for alcoholism: a survey of
      counselors and administrators in community-based addiction treatment centres.
AB  - AIMS: Medications, when combined with psychosocial therapy, can improve treatment
      outcomes in alcoholics; however, medications are not widely utilized in community
      based addiction treatment centres. Of interest is how non-medical addiction
      treatment professionals in these facilities view adjunctive pharmacotherapies for
      alcoholism. The present report focuses on baseline data collected during the
      course of an educational intervention project and explores predictors of positive
      attitudes about adjunctive pharmacotherapies among community addiction counselors
      and administrators. METHODS: Questionnaires were administered to 84 counselors
      and administrators at six community-based addiction treatment centres in South
      Carolina. Demographic data were collected, and knowledge and attitudes regarding
      the value of pharmacotherapies in the treatment of alcoholism were assessed.
      Correlation coefficients were explored, and follow-up multiple regression
      analyses were conducted to examine variables that predict scores reflecting the
      degree to which one values adjunctive pharmacotherapies for alcoholism. RESULTS:
      Respondents had little knowledge of naltrexone, with average test scores
      reflecting no better than chance performance. In addition, most participants
      believed that adjunctive pharmacotherapy is ineffectual. Higher valuation of
      adjunctive pharmacotherapy was related to knowledge about naltrexone, having a
      post-baccalaureate degree, and years of experience in the addictions treatment
      field. CONCLUSIONS: These data support that more widespread use of adjunctive
      pharmacotherapy for alcoholism may be impeded by the fact that addictions
      counselors, who are often the first contact for treatment-seeking individuals,
      have a lack of knowledge and a lack of confidence in the effectiveness of such
      treatments. Directed educational interventions are warranted for this population.

PMID- 17172259
TI  - Developmental changes in the expression of glycogenes and the content of N
      glycans in the mouse cerebral cortex.
AB  - Biosynthesis of N-glycans varies significantly among tissues and is strictly
      regulated spatially and temporally within the tissue. The strict molecular
      mechanisms that are responsible for control of N-glycan synthesis remain largely
      unknown. We developed complementary deoxyribonucleic acid (cDNA) macroarray
      system and analyzed gene expression levels of more than 140 glycosyltransferases
      and glycosidases in the cerebral cortex from developing and adult mice. We also
      analyzed the relative amounts of major N-glycans present in the cerebral cortex
      and examined how the synthesis of N-glycans might be regulated through the
      expression of these genes. We demonstrated that the content of N-linked
      oligosaccharides dramatically changed during the course of brain development.
      Some of these changes could not be explained by alterations in the expression of
      the corresponding genes. For example, the amount of core fucosylated sugar chains
      in the early embryonic brain and the expression level of fucosyltransferase VIII,
      the only gene known to be responsible for core fucosylation, did not change
      proportionately. This result suggests that post-transcriptional regulation of
      this gene plays an important role in regulating its enzymatic activity. On the
      other hand, the amount of beta1,3-galactose residue-containing sugar chains
      increased postnatally following an increase in the level of beta1,3
      galactosyltransferase messenger ribonucleic acid (mRNA). Furthermore, the amount
      of sugar chains with an outer fucose residue, containing LewisX-BA-2, correlated
      well with the expression of fusocyltransferase IX mRNA. These findings add to our
      understanding of the molecular mechanisms responsible for the regulation of N
      glycan biosynthesis in the cerebral cortex.

PMID- 17172260
TI  - Crystal structure of mammalian alpha1,6-fucosyltransferase, FUT8.
AB  - Mammalian alpha1,6-fucosyltransferase (FUT8) catalyses the transfer of a fucose
      residue from a donor substrate, guanosine 5'-diphosphate-beta-L-fucose to the
      reducing terminal N-acetylglucosamine (GlcNAc) of the core structure of an
      asparagine-linked oligosaccharide. Alpha1,6-fucosylation, also referred to as
      core fucosylation, plays an essential role in various pathophysiological events.
      Our group reported that FUT8 null mice showed severe growth retardation and
      emphysema-like lung-destruction as a result of the dysfunction of epidermal
      growth factor and transforming growth factor-beta receptors. To elucidate the
      molecular basis of FUT8 with respect to pathophysiology, the crystal structure of
      human FUT8 was determined at 2.6 A resolution. The overall structure of FUT8 was
      found to consist of three domains: an N-terminal coiled-coil domain, a catalytic
      domain, and a C-terminal SH3 domain. The catalytic region appears to be similar
      to GT-B glycosyltransferases rather than GT-A. The C-terminal part of the
      catalytic domain of FUT8 includes a Rossmann fold with three regions that are
      conserved in alpha1,6-, alpha1,2-, and protein O-fucosyltransferases. The SH3
      domain of FUT8 is similar to other SH3 domain-containing proteins, although the
      significance of this domain remains to be elucidated. The present findings of
      FUT8 suggest that the conserved residues in the three conserved regions
      participate in the Rossmann fold and act as the donor binding site, or in
      catalysis, thus playing key roles in the fucose-transferring reaction.

PMID- 17172261
TI  - Significant decrease in alpha1,3-linked fucose in association with increase in 6
      sulfated N-acetylglucosamine in peripheral lymph node addressin of FucT-VII
      deficient mice exhibiting diminished lymphocyte homing.
AB  - Lymphocyte homing is mediated by binding of L-selectin on lymphocytes with L
      selectin ligands present on high-endothelial venules (HEV) of peripheral and
      mesenteric lymph nodes. L-selectin ligands are specific O-linked carbohydrates, 6
      sulfo sialyl Lewis X, composed of sialylated, fucosylated, and sulfated glycans.
      Abrogation of fucosyltransferase-VII (FucT-VII) results in almost complete loss
      of lymphocyte homing, but structural analysis of carbohydrates has not been
      carried out on FucT-VII null mice. To determine whether functional losses seen in
      FucT-VII null mice are caused by structural changes in carbohydrates, we
      elucidated the carbohydrate structure of GlyCAM-1, a major L-selectin counter
      receptor. Our results show that most alpha1,3-fucosylated structures in 6-sulfo
      sialyl Lewis X are absent and 6-sulfo N-acetyllactosamine is increased in the
      mutant mice. Surprisingly, the amount of 6'-sulfated galactose (Gal) that bound
      to Sumbucus nigra agglutinin column was also increased. We found that structures
      of those oligosaccharides containing 6'-sulfated Gal are almost identical to
      those synthesized by keratan sulfate sulfotransferase (KSST). We then showed that
      overexpression of KSST suppresses the expression of sialyl Lewis X on Chinese
      hamster ovary (CHO) cells engineered to express sialyl Lewis X. Moreover, KSST
      expression in those cells suppressed lymphocyte rolling compared with mock
      transfected CHO cells expressing 6-sulfo sialyl Lewis X. 6'-Sulfo sialyl Lewis X
      can neither be found in GlyCAM-1 from CHO cells expressing both KSST and FucT-VII
      nor be found in GlyCAM-1 from HEV of mice. These results combined together
      suggest that KSST competes with FucT-VII for the same acceptor substrate and
      downregulates the synthesis of L-selectin ligand by inhibiting alpha1,3
      fucosylation.

PMID- 17172262
TI  - Polysialic acid bioengineering of neuronal cells by N-acyl sialic acid precursor
      treatment.
AB  - The inherent promiscuity of the polysialic acid (PSA) biosynthetic pathway has
      been exploited by the use of exogenous unnatural sialic acid precursor molecules
      to introduce unnatural modifications into cellular PSA, and has found
      applications in nervous system development and tumor vaccine studies. The sialic
      acid precursor molecules N-propionyl- and N-butanoyl-mannosamine (ManPr, ManBu)
      have been variably reported to affect PSA biosynthesis ranging from complete
      inhibition to de novo production of modified PSA, thus illustrating the need for
      further investigation into their effects. In this study, we have used a
      monoclonal antibody (mAb) 13D9, specific to both N-propionyl-PSA and N-butanoyl
      PSA (NPrPSA and NBuPSA), together with flow cytometry, to study precursor-treated
      tumor cells and NT2 neurons at different stages of their maturation. We report
      that both ManPr and ManBu sialic acid precursors are metabolized and the
      resultant unnatural sialic acids are incorporated into de novo surface
      sialylglycoconjugates in murine and human tumor cells and, for the first time, in
      human NT2 neurons. Furthermore, neither precursor treatment deleteriously
      affected endogenous PSA expression; however, with NT2 cells, PSA levels were
      naturally downregulated as a function of their maturation into polarized neurons
      independent of sialic acid precursor treatment.

PMID- 17172263
TI  - Effect of physiological concentration of urea on the conformation of human serum
      albumin.
AB  - We report that the presence of very low concentrations (<0.1 M) of urea, a widely
      used chemical denaturant, induces structure formation in the water-soluble
      globular protein human serum albumin (HSA) at pH 7. We have presented results
      suggesting an almost 8% and 5% increase in alpha-helix in the presence of 10 mM
      urea (U) and 20 mM monomethylurea (MMU), respectively. Far and near-UV circular
      dichroism studies along with tryptophan fluorescence and 1-anilino-8
      naphthalenesulphonicacid (ANS) binding support our view. We hypothesize that both
      U and MMU, at such low concentrations, modify the solvent structure, increase the
      dielectric constant and consequently increase hydrophobic forces resulting in
      enhanced alpha-helical content. The implications of these results of the lower
      urea regime are significant because the physiological blood urea ranges from 2.5
      to 7.5 mM.

PMID- 17172264
TI  - Identification and characterization of functional intermediates of stem bromelain
      during urea and guanidine hydrochloride unfolding.
AB  - By comparing changes in enzyme activity with changes in spectral features for
      stem bromelain (EC.3.4.22.32) in the absence and presence of urea, Guanidine
      hydrochloride and ethanol; four intermediate states could be identified: two
      activity-enhanced state obtained in the presence of 5 M urea and 2 M GnHCl,
      termed X and X', respectively, and a third, similarly active state closely
      resembling the native protein in the presence of 8-9 M urea, termed Y. The
      enhanced activity of these states is due to local conformational changes
      accompanied by increased dynamics in the active site. Further, the enzyme does
      not lose its activity after substantial tertiary structure changes in 8-9 M urea
      (Y state), suggesting that active site containing domain is more resistant to
      chemical denaturation than the other structural domain. This makes stem bromelain
      and in general cysteine proteases an exception to the hypothesis that active site
      is the most labile part of enzyme.

PMID- 17172265
TI  - Influence of a combination of random noise and pattern-edge width (in pixels) on
      contrast-to-gradient image resolution in scanning electron microscopy.
AB  - The contrast-to-gradient (CG) method has been proposed previously for the
      evaluation of image resolution in scanning electron microscopy (SEM). In the CG
      algorithm, the image to be evaluated is gradually reduced to form the 1/r-reduced
      image (r = 1, 2, 3, ...) until the representative features of local patterns are
      accurately recognizable after the corresponding r-th noise reduction. We have
      studied the influence of a combination of random noise and pattern-edge width (in
      pixels) on the CG resolution R using both PC-made test images and typical SEM
      images. As the random noise is larger, the value of R becomes larger (or poorer).
      The increase in R due to the noise influence is more significant for the narrower
      width of the pattern edge. This satisfactorily agrees with the common idea that
      the image resolution is to reflect the sharpness of the pattern edge recognized
      in the image noise. By revising the form of DeltaR from the weighted standard
      fluctuation of R to the differential of R, a significantly weak N(dot)-dependency
      on R has been favorably confirmed, with keeping firmly the noise-dependency on R.
      Here, N(dot) is the number of pattern dots in the image.

PMID- 17172266
TI  - Hypothermia-induced cardioprotection using extended ischemia and early
      reperfusion cooling.
AB  - Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our
      prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes
      can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes
      demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling
      that confer protection against I/R injury. Thus we hypothesized that hypothermia
      will protect most using extended ischemia and early reperfusion cooling and is
      mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an
      established model of 1-h ischemia/3-h reperfusion, and the same field of
      initially contracting cells was monitored for viability and NO generation.
      Normothermic I/R resulted in 49.7 +/- 3.4% cell death. Hypothermia induction to
      25 degrees C was most protective (14.3 +/- 0.6% death, P < 0.001 vs. I/R control)
      when instituted during extended ischemia and early reperfusion, compared with
      induction after reperfusion (22.4 +/- 2.9% death). Protection was completely lost
      if onset of cooling was delayed by 15 min of reperfusion (45.0 +/- 8.2% death).
      Extended ischemia/early reperfusion cooling was associated with increased and
      sustained NO generation at reperfusion and decreased caspase-3 activation. The
      NOS inhibitor N(omega)-nitro-L-arginine methyl ester (200 microM) reversed these
      changes and abrogated hypothermia protection. In addition, the PKCepsilon
      inhibitor myr-PKCepsilon v1-2 (5 microM) also reversed NO production and
      hypothermia protection. In conclusion, therapeutic hypothermia initiated during
      extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R
      injury. Such protection appears to be mediated by increased NO generation via
      activation of protein kinase Cepsilon; nitric oxide synthase.

PMID- 17172267
TI  - Role of oxidative stress in alterations of mitochondrial function in ischemic
      reperfused hearts.
AB  - To study the mechanisms of mitochondrial dysfunction due to ischemia-reperfusion
      (I/R) injury, rat hearts were subjected to 20 or 30 min of global ischemia
      followed by 30 min of reperfusion. After recording both left ventricular
      developed pressure (LVDP) and end-diastolic pressure (LVEDP) to monitor the
      status of cardiac performance, mitochondria from these hearts were isolated to
      determine respiratory and oxidative phosphorylation activities. Although hearts
      subjected to 20 min of ischemia failed to generate LVDP and showed a marked
      increase in LVEDP, no changes in mitochondrial respiration and phosphorylation
      were observed. Reperfusion of 20-min ischemic hearts depressed mitochondrial
      function significantly but recovered LVDP completely and lowered the elevated
      LVEDP. On the other hand, depressed LVDP and elevated LVEDP in 30-min ischemic
      hearts were associated with depressions in both mitochondrial respiration and
      oxidative phosphorylation. Reperfusion of 30-min ischemic hearts elevated LVEDP,
      attenuated LVDP, and decreased mitochondrial state 3 and uncoupled respiration,
      respiratory control index, ADP-to-O ratio, as well as oxidative phosphorylation
      rate. Alterations of cardiac performance and mitochondrial function in I/R hearts
      were attenuated or prevented by pretreatment with oxyradical scavenging mixture
      (superoxide dismutase and catalase) or antioxidants [N-acetyl-L-cysteine or N-(2
      mercaptopropionyl)-glycine]. Furthermore, alterations in cardiac performance and
      mitochondrial function due to I/R were simulated by an oxyradical-generating
      system (xanthine plus xanthine oxidase) and an oxidant (H(2)O(2)) either upon
      perfusing the heart or upon incubation with mitochondria. These results support
      the view that oxidative stress plays an important role in inducing changes in
      cardiac performance and mitochondrial function due to I/R.

PMID- 17172268
TI  - Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: implications
      for diseases in the cardiovascular system.
AB  - Reactive oxygen species (ROS) and the cellular thiol redox state are crucial
      mediators of multiple cell processes like growth, differentiation, and apoptosis.
      Excessive ROS production or oxidative stress is associated with several diseases,
      including cardiovascular disorders like ischemia-reperfusion. To prevent ROS
      induced disorders, the heart is equipped with effective antioxidant systems. Key
      players in defense against oxidative stress are members of the thioredoxin-fold
      family of proteins. Of these, thioredoxins and glutaredoxins maintain a reduced
      intracellular redox state in mammalian cells by the reduction of protein thiols.
      The reversible oxidation of Cys-Gly-Pro-Cys or Cys-Pro(Ser)-Tyr-Cys active site
      cysteine residues is used in reversible electron transport. Thioredoxins and
      glutaredoxins belong to corresponding systems consisting of NADPH, thioredoxin
      reductase, and thioredoxin or NADPH, glutathione reductase, glutathione, and
      glutaredoxin, respectively. Thioredoxin as well as glutaredoxin activities appear
      to be very important for the progression and severity of several cardiovascular
      disorders. These proteins function not only as antioxidants, they inhibit or
      activate apoptotic signaling molecules like apoptosis signal-regulating kinase 1
      and Ras or transcription factors like NF-kappaB. Thioredoxin activity is
      regulated by the endogenous inhibitor thioredoxin-binding protein 2 (TBP-2),
      indicating an important role of the balance between thioredoxin and TBP-2 levels
      in cardiovascular diseases. In this review, we will summarize cardioprotective
      effects of endogenous thioredoxin and glutaredoxin systems as well as the high
      potential in clinical applications of exogenously applied thioredoxin or
      glutaredoxin or the induction of endogenous thioredoxin and glutaredoxin systems.

PMID- 17172269
TI  - p38 mitogen-activated protein kinase mediates adenosine-induced alterations in
      myocardial glucose utilization via 5'-AMP-activated protein kinase.
AB  - Adenosine-induced acceleration of glycolysis in hearts stressed by transient
      ischemia is accompanied by suppression of glycogen synthesis and by increases in
      activity of adenosine 5'-monophosphate-activated protein kinase (AMPK). Because
      p38 mitogen-activated protein kinase (MAPK) may regulate glucose metabolism and
      may be activated downstream of AMPK, this study determined the effects of the p38
      MAPK inhibitors SB202190 and SB203580 on adenosine-induced alterations in glucose
      utilization and AMPK activity. Studies were performed in working rat hearts
      perfused aerobically following stressing by transient ischemia (2 x 10-min
      ischemia followed by 5-min reperfusion). Phosphorylation of AMPK and p38 MAPK
      each were increased fourfold by adenosine, and these effects were inhibited by
      either SB202190 or SB203580. Neither of these inhibitors directly affected AMPK
      activity. Attenuation of the adenosine-induced increase in AMPK and p38 MAPK
      phosphorylation by SB202190 and SB203580 occurred independently of any change in
      tissue ATP-to-AMP ratio and did not alter glucose uptake, but it was accompanied
      by an increase in glycogen synthesis and glycogen content and by inhibition of
      glycolysis and proton production. There was a significant inverse correlation
      between the rate of glycogen synthesis and AMPK activity and between AMPK
      activity and glycogen content. These data demonstrate that AMPK is likely
      downstream of p38 MAPK in mediating the effects of adenosine on glucose
      utilization in hearts stressed by transient ischemia. The ability of p38 MAPK
      inhibitors to relieve the inhibition of glycogen synthesis and to inhibit
      glycolysis and proton production suggests that these agents may restore adenosine
      induced cardioprotection in stressed hearts.

PMID- 17172270
TI  - Cold-induced cutaneous vasoconstriction is mediated by Rho kinase in vivo in
      human skin.
AB  - Cutaneous vasoconstriction (VC) is the initial thermoregulatory response to cold
      exposure and can be elicited through either whole body or localized skin cooling.
      However, the mechanisms governing local cold-induced VC are not well understood.
      We tested the hypothesis that Rho kinase participates in local cold-induced
      cutaneous VC. In seven men and women (20-27 yr of age), up to four ventral
      forearm skin sites were instrumented with intradermal microdialysis fibers for
      localized drug delivery during cooling. Skin blood flow was monitored at each
      site with laser-Doppler flowmetry while local skin temperature was decreased and
      maintained at 24 degrees C for 40 min. Cutaneous vascular conductance (CVC; laser
      Doppler flowmetry/mean arterial pressure) was expressed as percent change from 34
      degrees C baseline. During the first 5 min of cooling, CVC decreased at control
      sites (lactated Ringer solution) to -45 +/- 6% (P < 0.001), increased at
      adrenoceptor-antagonized sites (yohimbine + propranolol) to 15 +/- 14% (P =
      0.002), and remained unchanged at both Rho kinase-inhibited (fasudil) and
      adrenoceptor-antagonized + Rho kinase-inhibited sites (yohimbine + propranolol +
      fasudil) (-9 +/- 1%, P = 0.4 and -6 +/- 2%, P = 0.4, respectively). During the
      last 5 min of cooling, CVC further decreased at all sites when compared with
      baseline values (control, -77 +/- 4%, P < 0.001; adrenoceptor antagonized, -61 +/
      3%, P < 0.001; Rho kinase inhibited, -34 +/- 7%, P < 0.001; and adrenoceptor
      antagonized + Rho kinase inhibited sites, -35 +/- 3%, P < 0.001). Rho kinase
      inhibited and combined treatment sites were significantly attenuated when
      compared with both adrenoceptor-antagonized (P < 0.01) and control sites (P <
      0.0001). Rho kinase mediates both early- and late-phase cold-induced VC,
      supporting in vitro findings and providing a putative mechanism through which
      both adrenergic and nonadrenergic cold-induced VC occurs in an in vivo human
      thermoregulatory model.

PMID- 17172271
TI  - Mechanism of cardioventilatory coupling: insights from cardiac pacing, vagotomy,
      and sinoaortic denervation in the anesthetized rat.
AB  - Cardioventilatory coupling (CVC), a temporal alignment between the heartbeat and
      inspiratory activity, is a major determinant of breath-to-breath variation in
      observed respiratory rate (f(o)). The cardiac-trigger hypothesis attributes this
      to adjustments of respiratory timing by baroreceptor afferent impulses to the
      central respiratory pattern generator. A mathematical model of this hypothesis
      indicates that apparent CVC in graphical plots of ECG R wave vs. inspiratory time
      is dependent on the heart rate (HR), the rate of the intrinsic respiratory
      oscillator (f(i)), and the strength of the hypothetical cardiovascular afferent
      impulse. Failure to account for HR and f(i) may explain the inconsistent results
      from previous attempts to identify the neural pathways involved in CVC. Cognizant
      of these interactions, we factored in the HR-to-f(i) ratio in our examination of
      the role of the vagus nerve and arterial baroreceptors in CVC by cardiac pacing
      29 anesthetized Sprague-Dawley rats and incrementally changing the HR. With the
      assumption of a relatively constant f(i), CVC could be examined across a range of
      HR-to-f(o) ratios before and after vagotomy, sinoaortic denervation, and vagotomy
      + sinoaortic denervation. We confirmed the relation between CVC, HR-to-f(o)
      ratio, and breath-to-breath respiratory period variability and demonstrated the
      loss of these relations after baroreceptor elimination. Sham experiments (n = 8)
      showed that these changes were not due to surgical stress. Our data support the
      notion that inspiratory timing can be influenced by cardiac afferent activity. We
      conclude that the putative cardiovascular input arises from the arterial
      baroreceptors and that the vagus nerve is not critical for CVC.

PMID- 17172272
TI  - Endothelial nitric oxide synthase is a molecular vascular target for the Chinese
      herb Danshen in hypertension.
AB  - Danshen, a Chinese herb, reduces hypertension in Oriental medicine. We
      hypothesized that Danshen acts partially through endothelial nitric oxide
      synthase (eNOS) signaling mechanisms. We tested the hypothesis using tanshinone
      II(A), an active ingredient of Danshen, and the two-kidney, one-clip renovascular
      hypertension model in hamsters. Oral tanshinone (50 microg/100 g body wt) reduced
      mean arterial pressure (MAP) from 161.2 +/- 6.9 to 130.0 +/- 7.8 mmHg (mean +/-
      SE; P < 0.05) in hypertensive hamsters. MAP in sham-operated hamsters was 114.3
      +/- 9.2 mmHg. Topical tanshinone at 1 microg/ml and 5 microg/ml increased
      normalized arteriolar diameter from 1.00 to 1.25 +/- 0.08 and 1.57 +/- 0.11,
      respectively, and increased periarteriolar nitric oxide concentration from 87.1
      +/- 11.3 to 146.9 +/- 23.1 nM (P < 0.05) at 5 microg/ml in hamster cheek pouch.
      N(G)-monomethyl-L-arginine inhibited tanshinone-induced vasodilation.
      Hypertension reduced eNOS protein relative to sham-operated control. Tanshinone
      prevented the hypertension-induced reduction of eNOS and increased eNOS
      expression to levels higher than sham-operated control in hamster cheek pouch.
      Topical tanshinone increased normalized arteriolar diameter from 1.0 to 1.47 +/-
      0.08 in the cremaster muscle of control mice and to 1.12 +/- 0.13 in cremasters
      of eNOS knockout mice. In ECV-304 cells transfected with eNOS-green fluorescent
      protein, tanshinone increased eNOS protein expression 1.35 +/- 0.05- and 1.85 +/-
      0.07-fold above control after 5-min and 1-h application, respectively. Tanshinone
      also increased eNOS phosphorylation 1.19 +/- 0.07- and 1.72 +/- 0.20-fold
      relative to control after 5-min and 1-h application. Our data provide a basis to
      understand the action of a Chinese herb used in alternative medicine. We conclude
      that eNOS stimulation is one mechanism by which tanshinone induces vasodilation
      and reduces blood pressure.

PMID- 17172273
TI  - Cardiac neural crest ablation inhibits compaction and electrical function of
      conduction system bundles.
AB  - Retroviral and transgenic lineage-tracing studies have shown that neural crest
      cells associate with the developing bundles of the ventricular conduction system.
      Whereas this migration of cells does not provide progenitors for the myocardial
      cells of the conduction system, the question of whether neural crest affects the
      differentiation and/or function of cardiac specialized tissues continues to be of
      interest. Using optical mapping of voltage-sensitive dye, we determined that
      ventricles from chick embryos in which the cardiac neural crest had been laser
      ablated did not progress to apex-to-base activation by the expected stage [i.e.,
      Hamburger and Hamilton (HH) 35] but instead maintained basal breakthroughs of
      epicardial activation consistent with immature function of the conduction system.
      In direct studies of activation, waves of depolarization originating from the His
      bundle were found to be uncommon in control hearts from HH34 and HH35 embryos.
      However, activations propagating from septal base, at or near the His bundle,
      occurred frequently in hearts from HH34 and HH35 neural crest-ablated embryos.
      Consistent with His bundle cells maintaining electrical connections with adjacent
      working myocytes, histological analyses of hearts from neural crest-ablated
      embryos revealed His bundles that had not differentiated a lamellar organization
      or undergone a process of compaction and separation from surrounding myocardium
      observed in controls. Furthermore, measurements on histological sections from
      optically mapped hearts indicated that, whereas His bundle diameter in control
      embryos thinned by almost one-half between HH30 and HH34, the His bundle in
      ablated embryos underwent no such compaction in diameter, maintaining a thickness
      at HH30, HH32, and HH34 similar to that observed in HH30 controls. We conclude
      that the cardiac neural crest is required in a novel function involving lamellar
      compaction and electrical isolation of the basally located His bundle from
      surrounding myocardium.

PMID- 17172274
TI  - Length-tension relationships of small arteries, veins, and lymphatics from the
      rat mesenteric microcirculation.
AB  - The passive and active length-tension relationships of isolated rat mesenteric
      lymphatics ( approximately 150 microm ID), and adjacent small arteries (
      approximately 240 microm) and veins ( approximately 275 microm) were compared
      under isometric conditions using a wire myograph. About 60% of the lymphatic
      vessels developed spontaneous contractions in physiological saline solution at
      nominal preload. To maximally activate smooth muscle, 145 mM K(+) + 5 x 10(-5) M
      norepinephrine was used for arteries, and 145 mM K(+) + 1 x 10(-6) M substance P
      was used for lymphatics and veins. In response, arteries exhibited monotonic
      force development to a plateau level, whereas lymphatics and veins showed
      biphasic force development, consisting of a transient force peak followed by
      partial relaxation to a plateau over approximately 5 min. The passive and the
      active length-tension curves were similar in shape among all three vessels.
      However, the maximal active tension of arteries (3.4 +/- 0.42 mN/mm) was
      significantly greater than peak active tension (0.59 +/- 0.04 mN/mm) or plateau
      tension (0.20 +/- 0.04 mN/mm) in small veins and greater than peak active tension
      (0.34 +/- 0.02 mN/mm) or plateau tension (0.21 +/- 0.02 mN/mm) in lymphatics.
      Maximal active medial wall stress was similar between lymphatics and veins but
      was approximately fivefold higher in small arteries. For lymphatics, the pressure
      calculated from the optimal preload was significantly higher than that found
      previously in isobaric studies of isolated lymphatics, suggesting the capacity to
      operate at higher than normal pressures for increased responsiveness. Our results
      represent the first mechanical comparisons of arterial, venous, and lymphatic
      vessels in the same vasculature.

PMID- 17172276
TI  - Cardiac response to pressure overload in 129S1/SvImJ and C57BL/6J mice: temporal-
      and background-dependent development of concentric left ventricular hypertrophy.
AB  - Left ventricular hypertrophy (LVH), a risk factor for cardiovascular morbidity
      and mortality, is commonly caused by essential hypertension. Three geometric
      patterns of LVH can be induced by hypertension: concentric remodeling, concentric
      hypertrophy, and eccentric hypertrophy. Clinical studies suggest that different
      underlying etiologies, genetic modifiers, and risk of mortality are associated
      with LVH geometric patterns. Since pressure overload-induced LVH can be modeled
      experimentally using transverse aortic constriction (TAC) and since C57BL/6J (B6)
      and 129S1/SvImJ (129S1) strains, which have different baseline cardiovascular
      phenotypes, are commonly used, we conducted serial echocardiographic studies to
      assess cardiac function up to 8 wk of post-TAC in male B6, 129S1, and B6129F1
      (F1) mice. B6 mice had an earlier onset and more pronounced impairment in
      contractile function, with corresponding left and right ventricular dilatation,
      fibrosis, change in expression of hypertrophy marker, and increased liver weights
      at 5 wk of post-TAC. These observations suggest that B6 mice had eccentric
      hypertrophy with systolic dysfunction and right-sided heart failure. In contrast,
      we found that 129S1 and F1 mice delayed transition to decompensated heart
      failure, with 129S1 mice exhibiting preserved systolic function until 8 wk of
      post-TAC and relatively mild alterations in histology and markers of hypertrophy
      at 5 wk post-TAC. Consistent with concentric hypertrophy, our results show that
      these strains manifest different cardiac responses to pressure overload in a time
      dependent manner and that genetic susceptibility to initial concentric
      hypertrophy is dominant to eccentric hypertrophy. These results also imply that
      genetic background differences can complicate interpretation of TAC studies when
      using mixed genetic backgrounds.

PMID- 17172275
TI  - Phosphatidylinositol 3-kinase/protein kinase Akt negatively regulates plasminogen
      activator inhibitor type 1 expression in vascular endothelial cells.
AB  - Plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolytic activity
      and mediates vascular atherothrombotic disease. Endothelial cells (ECs)
      synthesize and secrete PAI-1, but the intracellular signaling pathways that
      regulate PAI-1 expression are not entirely known. We hypothesize that the
      phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt pathway, which regulates
      endothelial function, could modulate PAI-1 expression in ECs. Cultured bovine
      aortic and human saphenous vein ECs were stimulated with TNF-alpha, ANG II,
      insulin, or serum, and PAI-1 expression was determined by Northern and Western
      analyses. Inhibition of PI3K with wortmannin or LY-294002 enhanced PAI-1
      expression induced by these extracellular stimuli. Similarly, overexpression of a
      dominant-negative mutant of PI3K or Akt increased TNF-alpha- and insulin-induced
      PAI-1 expression. The increase in PAI-1 was due to transcriptional and
      posttranscriptional mechanisms as PI3K inhibitors increased PAI-1 promoter
      activity and mRNA stability. The induction of PAI-1 by TNF-alpha and insulin is
      mediated, in part, by ERK and p38 MAPK. PI3K inhibitors augmented TNF-alpha- and
      insulin-induced phosphorylation of these MAPKs. Simvastatin, a 3-hydroxy-3
      methylglutaryl-CoA reductase inhibitor, which is known to activate PI3K/Akt,
      blocks TNF-alpha- and insulin-induced PAI-1 expression. Treatment with PI3K
      inhibitors reversed the inhibitor effects of simvastatin on TNF-alpha- and
      insulin-induced PAI-1 expression. These findings indicate that the PI3K/Akt
      pathway acts as a negative regulator of PAI-1 expression in ECs, in part, through
      the downregulation of MAPK pathways. These results suggest that factors that
      activate the PI3K/Akt pathway in ECs may have therapeutic benefits for
      atherothrombotic vascular disease.

PMID- 17172277
TI  - The olive oil antioxidant hydroxytyrosol efficiently protects against the
      oxidative stress-induced impairment of the NObullet response of isolated rat
      aorta.
AB  - The Mediterranean diet, which is abundant in antioxidants, is associated with a
      relatively low incidence of coronary heart disease. Olive oil and olives, which
      contain the antioxidants hydroxytyrosol, oleuropein, and tyrosol, are important
      components of this diet. In this study, the effects of oxidative stress on the
      nitric oxide radical (NO(*))-mediated relaxation of rat aorta and the protection
      by these antioxidants were determined. Cumene hydroperoxide (CHP) was used to
      mimic oxidative stress induced by lipid hydroperoxides, which is mediated by the
      formation of hydroxyl radicals (OH(*)). CHP (300 microM) impaired the NO(*)
      mediated relaxation of rat aorta by the acetylcholine receptor agonist carbachol
      (P < 0.05). This was due to a reduction in NO(*) production. A diminished NO(*)
      mediated relaxation disturbs the vascular tone and leads to a rise in blood
      pressure, which is a well-established risk factor for coronary heart disease.
      Hydroxytyrosol (10 microM) efficiently protected the aorta against the CHP
      induced impairment of the NO(*)-mediated relaxation (P < 0.05). Oleuropein,
      tyrosol, and homovanillic alcohol, a major metabolite of hydroxytyrosol, did not
      show protection. Moreover, hydroxytyrosol was found to be a potent OH(*)
      scavenger, which can be attributed to its catechol moiety. Because of its
      amphiphilic characteristics (octanol-water partitioning coefficient = 1.1),
      hydroxytyrosol will readily cross membranes and provide protection in the cytosol
      and membranes, including the water-lipid interface. The present study provides a
      molecular basis for the contribution of hydroxytyrosol to the benefits of the
      Mediterranean diet.

PMID- 17172278
TI  - Real-time imaging of mechanically injured femoral artery in mice reveals a
      biphasic pattern of leukocyte accumulation.
AB  - Wire injury of an artery has been recognized as a standard model of vascular
      inflammation and atherosclerosis; however, the mechanism of leukocyte recruitment
      has not been studied in this model. In this study, we documented the recruitment
      of leukocytes to the murine femoral artery after a wire injury. A transluminal
      mechanical injury was generated by insertion of a wire into the femoral artery of
      male C57BL/6J mice. The mice were anesthetized and ventilated after tracheotomy
      and protected from hypothermia by a warming lamp. Body temperature and blood pH
      did not significantly change during the experiment. The interaction between
      rhodamine 6G-labeled leukocytes and the injured femoral artery was monitored
      using an epifluorescent microscope, and the images were evaluated using a
      computer-assisted image analysis program. In the absence of injury, virtually no
      leukocyte adhesion was observed. In contrast, the number of adherent leukocytes
      increased 4 and 24 h after injury and declined 72 h after injury. The rolling
      flux of leukocytes increased 4 h after injury and remained high up to 7 days, but
      it was faster 72 h after injury. We identified another peak of leukocyte adhesion
      7 days after injury. Injection of anti-P-selectin antibody significantly reduced
      leukocyte adhesion at the early and later phases. In conclusion, we have
      established a novel experimental system for direct observation of leukocyte
      recruitment to the injured femoral artery. Our system revealed a previously
      undetected, unique profile of leukocyte recruitment during vascular injury.

PMID- 17172279
TI  - Intermittent peripheral tissue ischemia during coronary ischemia reduces
      myocardial infarction through a KATP-dependent mechanism: first demonstration of
      remote ischemic perconditioning.
AB  - Remote ischemic preconditioning reduces myocardial infarction (MI) in animal
      models. We tested the hypothesis that the systemic protection thus induced is
      effective when ischemic preconditioning is administered during ischemia (PerC)
      and before reperfusion and examined the role of the K(+)-dependent ATP (K(ATP))
      channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left
      anterior descending coronary artery occlusion with 120 min of reperfusion. PerC
      consisted of four 5-min cycles of lower limb ischemia by tourniquet during left
      anterior descending coronary artery occlusion. Left ventricular (LV) function was
      assessed by a conductance catheter and extent of infarction by tetrazolium
      staining. The extent of MI was significantly reduced by PerC (60.4 +/- 14.3 vs.
      38.3 +/- 15.4%, P = 0.004) and associated with improved functional indexes. The
      increase in the time constant of diastolic relaxation was significantly
      attenuated by PerC compared with control in ischemia and reperfusion (P = 0.01
      and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke
      work declined 38 +/- 6% and 3 +/- 5% in control and PerC, respectively (P =
      0.001). The force-frequency relation was significantly depressed at 120 min of
      reperfusion in both groups, but optimal heart rate was significantly lower in the
      control group (P = 0.04). There were fewer malignant arrhythmias with PerC during
      reperfusion (P = 0.02). These protective effects of PerC were abolished by
      glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI,
      preserves global systolic and diastolic function, and protects against arrhythmia
      during the reperfusion phase through a K(ATP) channel-dependent mechanism.
      Understanding this process may have important therapeutic implications for a
      range of ischemia-reperfusion syndromes.

PMID- 17172280
TI  - Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition prevents endothelin A
      receptor antagonism in rat aorta.
AB  - This study tested whether sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase
      regulates the ability of endothelin receptor antagonist to inhibit the endothelin
      1 constriction. The endothelin A receptor antagonist BQ-123 (1 microM) completely
      relaxed constriction to 10 nM endothelin-1 in endothelium-denuded rat aorta.
      Challenge with cyclopiazonic acid (10 microM), a sarcoplasmic-endoplasmic
      reticulum Ca(2+)-ATPase inhibitor, during the plateau of endothelin-1
      constriction enhanced the constriction by approximately 30%. BQ-123 relaxed the
      endothelin-1 plus cyclopiazonic acid constriction by only approximately 10%. In
      contrast, prazosin (1 microM), an alpha-adrenergic receptor antagonist, still
      completely relaxed the 0.3 muM phenylephrine constriction in the presence of
      cyclopiazonic acid. Verapamil relaxed the endothelin-1 plus cyclopiazonic acid
      constriction by approximately 30%, whereas Ni(2+) and 2-aminoethoxydiphenyl
      borate, nonselective cation channel and store-operated channel blockers,
      respectively, completely relaxed the constriction. These results suggest that
      lowered sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase activity selectively
      decreases the ability of endothelin receptor antagonist to inhibit the endothelin
      A receptor. The decreased antagonism may be related to the opening of store
      operated channels and subsequent greater internalization of endothelin A
      receptor.

PMID- 17172281
TI  - Evaluation of a radiation protection cabin for invasive electrophysiological
      procedures.
AB  - AIMS: Complex invasive electrophysiological procedures may result in high
      cumulative operator radiation exposure. Classical protection with lead aprons
      results in discomfort while radioprotection is still incomplete. This study
      evaluated the usefulness of a radiation protection cabin (RPC) that completely
      surrounds the operator. METHODS AND RESULTS: The evaluation was performed
      independently in two electrophysiology laboratories (E1-Leuven, Belgium; E2
      Bordeaux, France), comparing operator radiation exposure using the RPC vs. a 0.5
      mm lead-equivalent apron (total of 135 procedures). E1 used thermoluminiscent
      dosimeters (TLDs) placed at 16 positions in and out of the RPC and nine positions
      in and out of the apron. E2 used more sensitive electronic personal dosimeters
      (EPD), placed at waist and neck. The sensitivity thresholds of the TLDs and EPDs
      were 10-20 microSv and 1-1.5 microSv, respectively. All procedures could be
      performed unimpeded with the RPC. Median TLD dose values outside protected areas
      were in the range of 57-452 microSv, whereas doses under the apron or inside the
      RPC were all at the background radiation level, irrespective of procedure and
      fluoroscopy duration and of radiation energy delivered. In addition, the RPC was
      protecting the entire body (except the hands), whereas lead apron protection is
      incomplete. Also with the more sensitive EPDs, the radiation dose within the RPC
      was at the sensitivity threshold/background level (1.3+/-0.6 microSv). Again,
      radiation to the head was significantly lower within the RPC (1.9+/-1.2 microSv)
      than with the apron (102+/-23 microSv, P<0.001). CONCLUSION: The use of the RPC
      allows performing catheter ablation procedures without compromising catheter
      manipulation, and with negligible radiation exposure for the operator.

PMID- 17172282
TI  - The preconceptual contraception paradigm: obesity and infertility.
AB  - Obesity is a major health problem across the world. Recent editorials suggest
      that obese patients should be denied treatment of any kind aimed to improve
      ovulation rates and achieve pregnancy until they have reduced their BMI. We
      propose that this approach is not a resolution of the problem, but indeed may
      amplify the maternal and perinatal complications attributed to fertility centres.
      Obesity independent of polycystic ovary syndrome (PCOS) is associated with
      anovulation, and minimal weight loss alone is an effective therapy for induction
      of ovulation in both obese women and obese PCOS women. Consequently, lifestyle
      programmes encouraging weight loss should be considered to be an ovulation
      induction therapy and due consideration for a potential pregnancy in an obese
      woman given. We propose that women with a BMI in excess of 35 kg m(2) should lose
      weight prior to conception-not prior to receiving infertility treatment.
      Therefore, clinicians undertaking the management of infertility in obese women
      should adopt measures to reduce their body mass prior to exposing them to the
      risks of pregnancy. We advocate that this approach should be aggressively managed
      including pharmacological strategies; intrinsic in this programme is the use of
      contraception and high-dose folic acid during that period of preconceptual weight
      reduction.

PMID- 17172283
TI  - Testicular sperm extraction in cancerous testicle in patients with azoospermia: a
      case report.
AB  - The aim of this study is to evaluate the feasibility of testicular sperm
      extraction (TESE) in a cancerous testicle during orchiectomy for testicular
      neoplasm. This is a retrospective study and includes case histories of four
      azoospermic patients with incidental testicular cancer. None of the patients had
      fathered children prior to surgery and all patients were strongly motivated by
      the desire to have offspring. Patients underwent surgical exploration via
      inguinotomy and spermatic cord clamping. After nodule excision, micro-TESE was
      performed from the same albugineal incision, under microscopic guidance. Frozen
      section examination was not performed in the case of large nodules (>3 cm in
      diameter). Two patients showed classic seminoma and underwent orchiectomy. In two
      patients, a Leydig cell tumour was found (one patient underwent orchiectomy for
      large nodule size). Micro-TESE was performed in four patients. Spermatozoa were
      found in three patients and the retrieved sperm was cryopreserved. One ICSI cycle
      was performed, but pregnancy failed. In azoospermic patients with testicular
      nodules, TESE in the cancerous testis is feasible and may avoid further surgery,
      without any oncological risk.

PMID- 17172284
TI  - GnRH agonist treatment in girls with precocious puberty does not compromise post
      pubertal uterine size.
AB  - BACKGROUND: Prompted by findings of a hypoestrogenic state in girls during
      prolonged treatment with GnRH agonist and a close association of estradiol serum
      concentrations with uterine volume in puberty, this study sought to evaluate
      uterine and ovarian size in girls with precocious puberty (PP) during and after
      treatment and the effect of age or duration of treatment. METHODS: Patients with
      idiopathic central PP before (n = 75), during (n = 41) or after (n = 30)
      treatment with GnRH agonist underwent transabdominal pelvic ultrasound
      examination. Findings were compared with those in 69 girls with epilepsy and no
      PP before initiation of anticonvulsant treatment. RESULTS: The girls with PP had
      significantly greater uterine and ovarian volumes before, during and after
      treatment with GnRH agonist than the controls, after adjusting for age at
      examination, weight, height and pubic and breast status. The average interval
      between the last treatment and the ultrasound examination was 1.3 years. There
      was no significant correlation between age at first treatment and uterine volume
      after treatment. Uterine volume decreased during treatment. There was a
      significant negative correlation between treatment duration and uterine volume
      after treatment (R(2) = -0.175, P = 0.024). Nevertheless, mean uterine volume was
      still greater in the treated group than in the control group (P = 0.002).
      CONCLUSION: The iatrogenic hypoestrogenic state in treated girls with PP does not
      compromise post-pubertal uterine size.

PMID- 17172285
TI  - Monitoring reproductive health in Europe: what are the best indicators of
      reproductive health? A need for evidence-based quality indicators of reproductive
      health care.
AB  - Monitoring reproductive health by the Reprostat indicators in Europe will
      facilitate the transparency of reproductive health as well as comparisons over
      time and between countries. However, for the monitoring and improvement of
      reproductive health care, we suggest the systematic development of evidence-based
      quality indicators, especially process and structure indicators.

PMID- 17172286
TI  - Nitrogen-dependent posttranscriptional regulation of the ammonium transporter
      AtAMT1;1.
AB  - Ammonium transporter (AMT) proteins of the AMT family mediate the transport of
      ammonium across plasma membranes. To investigate whether AMTs are regulated at
      the posttranscriptional level, a gene construct consisting of the cauliflower
      mosaic virus 35S promoter driving the Arabidopsis (Arabidopsis thaliana) AMT1;1
      gene was introduced into tobacco (Nicotiana tabacum). Ectopic expression of
      AtAMT1;1 in transgenic tobacco lines led to high transcript levels and protein
      levels at the plasma membrane and translated into an approximately 30% increase
      in root uptake capacity for 15N-labeled ammonium in hydroponically grown
      transgenic plants. When ammonium was supplied as the major nitrogen (N) form but
      at limiting amounts to soil-grown plants, transgenic lines overexpressing
      AtAMT1;1 did not show enhanced growth or N acquisition relative to wild-type
      plants. Surprisingly, steady-state transcript levels of AtAMT1;1 accumulated to
      higher levels in N-deficient roots and shoots of transgenic tobacco plants in
      spite of expression being controlled by the constitutive 35S promoter. Moreover,
      steady-state transcript levels were decreased after addition of ammonium or
      nitrate in N-deficient roots, suggesting a role for N availability in regulating
      AtAMT1;1 transcript abundance. Nitrogen deficiency-dependent accumulation of
      AtAMT1;1 mRNA was also observed in 35S:AtAMT1;1-transformed Arabidopsis shoots
      but not in roots. Evidence for a regulatory role of the 3'-untranslated region of
      AtAMT1;1 alone in N-dependent transcript accumulation was not found. However,
      transcript levels of AtAMT1;3 did not accumulate in a N-dependent manner, even
      though the same T-DNA insertion line atamt1;1-1 was used for 35S:AtAMT1;3
      expression. These results show that the accumulation of AtAMT1;1 transcripts is
      regulated in a N- and organ-dependent manner and suggest mRNA turnover as an
      additional mechanism for the regulation of AtAMT1;1 in response to the N
      nutritional status of plants.

PMID- 17172287
TI  - Functional diversification of acyl-coenzyme A oxidases in jasmonic acid
      biosynthesis and action.
AB  - The biosynthesis of jasmonic acid (JA) in plant peroxisomes requires the action
      of acyl-coenzyme A oxidase (ACX). Among the five expressed members (ACX1-5) of
      the ACX gene family in Arabidopsis (Arabidopsis thaliana), only ACX1 is known to
      serve a role in JA production. Here, we used transgenic promoter-reporter lines
      to show that ACX1 is highly expressed in mature and germinating pollen, stem
      epidermal cells, and other tissues in which jasmonate-signaled processes occur.
      Wound-induced JA accumulation was reduced in a mutant that is defective in ACX1
      and was abolished in a mutant that is impaired in both ACX1 and its closely
      related paralog, ACX5. The severe JA deficiency in acx1/5 double mutants was
      accompanied by decreased resistance to the leaf-eating insect Trichoplusia ni.
      The double mutant also showed reduced pollen viability and fecundity. Treatment
      of acx1/5 plants with JA restored both protection against T. ni larvae and normal
      seed set. Unexpectedly, acx1/5 plants accumulated JA in response to infection by
      the necrotrophic fungal pathogen Alternaria brassicicola. In contrast to mutants
      that are impaired in jasmonate perception or early steps of the JA biosynthetic
      pathway, acx1/5 plants maintained resistance to A. brassicicola infection. These
      results indicate that ACX1/5-mediated JA synthesis is essential for resistance to
      chewing insects and male reproductive function and further suggest that other ACX
      isozymes contribute to JA production in response to A. brassicicola challenge.
      Thus, different types of biotic stress may induce JA synthesis via distinct
      enzymatic routes.

PMID- 17172288
TI  - A comprehensive analysis of the 14-3-3 interactome in barley leaves using a
      complementary proteomics and two-hybrid approach.
AB  - This study describes the identification of over 150 target proteins of the five
      14-3-3 isoforms in 7-d-old barley (Hordeum vulgare) cv Himalaya seedlings using
      yeast two-hybrid screens complemented with 14-3-3 protein affinity purification
      and tandem mass spectrometry. Independent experiments for a subset of genes
      confirmed the yeast two-hybrid interactions, demonstrating a low false positive
      identification rate. These combined approaches resulted in the identification of
      more than 150 putative targets; 15% were previously reported to be 14-3-3
      interactors, including, for example, Serpin, RF2A, WPK4 kinase, P-type proton
      translocating adenosine triphosphatase, EF1A, glutamine synthetase, and
      invertases. The affinity purification resulted in 30 interactors, of which 44%
      function in metabolism, while the yeast two-hybrid screens identified 132
      different proteins, with 35% of the proteins involved in signal transduction. A
      number of proteins have a well-described function in hormonal signaling, such as
      the auxin transport protein PIN1 and NPH3 and components of the brassinosteroid
      pathway, such as the receptor kinase BAK1 (OsPERK1) and BRI1-kinase domain
      interacting protein 129. However, 14-3-3 interactions with these signal mediators
      have not been confirmed in the affinity purification. Confirmations of the 14-3-3
      interaction with the three ABF-like transcription factors are shown using far
      western analysis. Also, a REPRESSION OF SHOOT GROWTH ortholog named RF2A was
      identified; these transcription factors play important roles in the abscisic acid
      and gibberellin pathways, respectively. We speculate that 14-3-3 proteins have a
      role in cross talk between these hormonal pathways. The specificity and
      complementary nature of both the affinity purification and the yeast two-hybrid
      approaches is discussed.

PMID- 17172289
TI  - The Mi-9 gene from Solanum arcanum conferring heat-stable resistance to root-knot
      nematodes is a homolog of Mi-1.
AB  - Resistance conferred by the Mi-1 gene from Solanum peruvianum is effective and
      widely used for limiting root-knot nematode (Meloidogyne spp.) yield loss in
      tomato (Solanum lycopersicum), but the resistance is ineffective at soil
      temperatures above 28 degrees C. Previously, we mapped the heat-stable resistance
      gene Mi-9 in Solanum arcanum accession LA2157 to the short arm of chromosome 6,
      in a genetic interval as Mi-1 and the Cladosporium fulvum resistance gene Cf2. We
      developed a fine map of the Mi-9 region by resistance and marker screening of an
      F2 population and derived F3 families from resistant LA2157 x susceptible LA392.
      Mi-1 intron 1 flanking primers were designed to amplify intron 1 and fingerprint
      Mi-1 homologs. Using these primers, we identified seven Mi-1 homologs in the
      mapping parents. Cf-2 and Mi-1 homologs were mapped on chromosome 6 using a
      subset of the F2. Cf-2 homologs did not segregate with Mi-9 resistance, but three
      Mi-1 homologs (RH1, RH2, and RH4) from LA2157 and one (SH1) from LA392
      colocalized to the Mi-9 region. Reverse transcriptase-polymerase chain reaction
      analysis indicated that six Mi-1 homologs are expressed in LA2157 roots. We
      targeted transcripts of Mi-1 homologs for degradation with tobacco (Nicotiana
      tabacum) rattle virus (TRV)-based virus-induced gene silencing using
      Agrobacterium infiltration with a TRV-Mi construct. In most LA2157 plants
      infiltrated with the TRV-Mi construct, Mi-9-mediated heat-stable root-knot
      nematode resistance was compromised at 32 degrees C, indicating that the heat
      stable resistance is mediated by a homolog of Mi-1.

PMID- 17172290
TI  - Saponin biosynthesis in Saponaria vaccaria. cDNAs encoding beta-amyrin synthase
      and a triterpene carboxylic acid glucosyltransferase.
AB  - Saponaria vaccaria (Caryophyllaceae), a soapwort, known in western Canada as
      cowcockle, contains bioactive oleanane-type saponins similar to those found in
      soapbark tree (Quillaja saponaria; Rosaceae). To improve our understanding of the
      biosynthesis of these saponins, a combined polymerase chain reaction and
      expressed sequence tag approach was taken to identify the genes involved. A cDNA
      encoding a beta-amyrin synthase (SvBS) was isolated by reverse transcription
      polymerase chain reaction and characterized by expression in yeast (Saccharomyces
      cerevisiae). The SvBS gene is predominantly expressed in leaves. A S. vaccaria
      developing seed expressed sequence tag collection was developed and used for the
      isolation of a full-length cDNA bearing sequence similarity to ester-forming
      glycosyltransferases. The gene product of the cDNA, classified as UGT74M1, was
      expressed in Escherichia coli, purified, and identified as a triterpene
      carboxylic acid glucosyltransferase. UGT74M1 is expressed in roots and leaves and
      appears to be involved in monodesmoside biosynthesis in S. vaccaria.

PMID- 17172291
TI  - The rice kinase database. A phylogenomic database for the rice kinome.
AB  - The rice (Oryza sativa) genome contains 1,429 protein kinases, the vast majority
      of which have unknown functions. We created a phylogenomic database
      (http://rkd.ucdavis.edu) to facilitate functional analysis of this large gene
      family. Sequence and genomic data, including gene expression data and protein
      protein interaction maps, can be displayed for each selected kinase in the
      context of a phylogenetic tree allowing for comparative analysis both within and
      between large kinase subfamilies. Interaction maps are easily accessed through
      links and displayed using Cytoscape, an open source software platform.
      Chromosomal distribution of all rice kinases can also be explored via an
      interactive interface.

PMID- 17172293
TI  - Photophysics of Clomeleon by FLIM: discriminating excited state reactions along
      neuronal development.
AB  - In this work, fluorescence lifetime imaging microscopy in the time domain was
      used to study the fluorescence dynamics of ECFP and of the ratiometric chloride
      sensor Clomeleon along neuronal development. The multiexponential analysis of
      fluorophores combined with the study of the contributions of the individual
      lifetimes (decay-associated spectra) was used to discriminate the presence of
      energy transfer from other excited state reactions. A characteristic change of
      sign of the pre-exponential factors of lifetimes from positive to negative near
      the acceptor emission maxima was observed in presence of energy transfer. By
      fluorescence lifetime imaging microscopy, we could show that the individual
      conformations of CFP display differential quenching properties depending on their
      microenvironment. Suitability of Clomeleon as an optical indicator to obtain a
      direct readout of the intracellular chloride concentrations in living cells was
      verified by steady-state and time-resolved spectroscopy. The simultaneous study
      of the photophysical properties of Clomeleon, the calcium indicator Cameleon, and
      ECFP with neuronal development provided a kinetic model for the mechanism when
      competitive quenching effects as well as energy transfer occur in the same
      molecule. Simultaneous analysis of donor and acceptor kinetics was necessary to
      discriminate Forsters resonance energy transfer along neuronal development due to
      the different cellular effects involved.

PMID- 17172292
TI  - Cav3.1 (alpha1G) controls von Willebrand factor secretion in rat pulmonary
      microvascular endothelial cells.
AB  - The T-type Ca2+ channel Cav3.1 subunit is present in pulmonary microvascular
      endothelial cells (PMVECs), but not in pulmonary artery endothelial cells
      (PAECs). The present study sought to assess the role of Cav3.1 in thrombin
      induced Weibel-Palade body exocytosis and consequent von Willebrand factor (VWF)
      release. In PMVECs and PAECs transduced with a green fluorescent protein (GFP)
      tagged VWF chimera, we examined the real-time dynamics and secretory process of
      VWF-GFP-containing vesicles in response to thrombin and the cAMP-elevating agent
      isoproterenol. Whereas thrombin stimulated a progressive decrease in the number
      of VWF-GFP-containing vesicles in both cell types, isoproterenol only decreased
      the number of VWF-GFP-containing vesicles in PAECs. In PMVECs, thrombin-induced
      decrease in the number of VWF-GFP-containing vesicles was nearly abolished by the
      T-type Ca2+ channel blocker mibefradil as well as by Cav3.1 gene silencing with
      small hairpin RNA. Expression of recombinant Cav3.1 subunit in PAECs resulted in
      pronounced increase in thrombin-stimulated Ca2+ entry, which is sensitive to
      mibefradil. Together, these data indicate that VWF secretion from lung
      endothelial cells is regulated by two distinct pathways involving Ca2+ or cAMP,
      and support the hypothesis that activation of Cav3.1 T-type Ca2+ channels in
      PMVECs provides a unique cytosolic Ca2+ source important for Gq-linked agonist
      induced VWF release.

PMID- 17172294
TI  - The pH-dependent conformational states of kyotorphin: a constant-pH molecular
      dynamics study.
AB  - An extensive conformational study of the analgesic dipeptide kyotorphin (L-Tyr-L
      Arg) at different pH values was performed using a constant-pH molecular dynamics
      method. This dipeptide showed a remarkable pH-dependent conformational variety.
      The protonation of the N-terminal amine was identified as a key element in the
      transition between the more extended and the more packed conformational states,
      as monitored by the dihedral angle defined by the atoms 1Cbeta-1Calpha-2Calpha
      2Cbeta. The principal-component analysis of kyotorphin identified two major
      conformational populations (the extended trans and the packed cis) together with
      conformations that occur exclusively at extreme pH values. Other, less stable
      conformations were also identified, which help us to understand the transitions
      between the predominant populations. The fitting of kyotorphin's conformational
      space to the structure of morphine resulted in a set of conformers that were able
      to fulfill most of the constraints for the mu-receptor. These results suggest
      that there may be strong similarities between the kyotorphin receptor and the
      structural family of opioid receptors.

PMID- 17172295
TI  - Beta-sheet containment by flanking prolines: molecular dynamic simulations of the
      inhibition of beta-sheet elongation by proline residues in human prion protein.
AB  - Previous molecular dynamic simulations have reported elongation of the existing
      beta-sheet in prion proteins. Detailed examination has shown that these
      elongations do not extend beyond the proline residues flanking these beta-sheets.
      In addition, proline has also been suggested to possess a possible structural
      role in preserving protein interaction sites by preventing invasion of
      neighboring secondary structures. In this work, we have studied the possible
      structural role of the flanking proline residues by simulating mutant structures
      with alternate substitution of the proline residues with valine. Simulations
      showed a directional inhibition of elongation, with the elongation progressing in
      the direction of valine including evident inhibition of elongation by existing
      proline residues. This suggests that the flanking proline residues in prion
      proteins may have a containment role and would confine the beta-sheet within a
      specific length.

PMID- 17172296
TI  - Folding stability and cooperativity of the three forms of 1-110 residues fragment
      of staphylococcal nuclease.
AB  - Folding stability and cooperativity of the three forms of 1-110 residues fragment
      of staphylococcal nuclease (SNase110) have been studied by various biophysical
      and NMR methods. Samples of G-88W- and V-66W-mutant SNase110, namely G-88W110 and
      V-66W110, in aqueous solution and SNase110 in 2.0 M TMAO are adopted in this
      study. The unfolding transitions and folded conformations of the three SNase
      fragments were detected by far- and near-ultraviolet circular dichroism and
      intrinsic tryptophan fluorescence measurements. The tertiary structures and
      internal motions of the fragments were determined by NMR spectroscopy. Both G-88W
      and V-66W single mutations as well as a small organic osmolyte (Trimethylamine N
      oxide, TMAO) can fold the fragment into a native-like conformation. However, the
      tertiary structures of the three fragments exhibit different degrees of folding
      stability and compactness. G-88W110 adopts a relatively rigid structure
      representing a most stable native-like beta-subdomain conformation of the three
      fragments. V-66W110- and TMAO-stabilized SNase110 produce less compact structures
      having a less stable "beta-barrel" structural region. The different folding
      status accounts for the different backbone dynamic and urea-unfolding transition
      features of the three fragments. The G-20I/G-29I-mutant variants of the three
      fragments have provided the evidence that the folding status is correlated
      closely to the packing of the beta-strands in the beta-barrel of the fragments.
      The native-like beta-barrel structural region acts as a nonlocal nucleus for
      folding the fragment. The tertiary folding of the three fragments is initiated by
      formation of the local nucleation sites at two beta-turn regions, I-18-D-21 and Y
      27-Q-30, and developed by the formation of a nonlocal nucleation site at the beta
      barrel region. The formation of beta-barrel and overall structure is concerted,
      but the level of cooperativity is different for the three 1-110 residues SNase
      fragments.

PMID- 17172297
TI  - High apparent dielectric constant inside a protein reflects structural
      reorganization coupled to the ionization of an internal Asp.
AB  - The dielectric properties of proteins are poorly understood and difficult to
      describe quantitatively. This limits the accuracy of methods for structure-based
      calculation of electrostatic energies and pK(a) values. The pK(a) values of many
      internal groups report apparent protein dielectric constants of 10 or higher.
      These values are substantially higher than the dielectric constants of 2-4
      measured experimentally with dry proteins. The structural origins of these high
      apparent dielectric constants are not well understood. Here we report on
      structural and equilibrium thermodynamic studies of the effects of pH on the V66D
      variant of staphylococcal nuclease. In a crystal structure of this protein the
      neutral side chain of Asp-66 is buried in the hydrophobic core of the protein and
      hydrated by internal water molecules. Asp-66 titrates with a pK(a) value near 9.
      A decrease in the far UV-CD signal was observed, concomitant with ionization of
      this aspartic acid, and consistent with the loss of 1.5 turns of alpha-helix.
      These data suggest that the protein dielectric constant needed to reproduce the
      pK(a) value of Asp-66 with continuum electrostatics calculations is high because
      the dielectric constant has to capture, implicitly, the energetic consequences of
      the structural reorganization that are not treated explicitly in continuum
      calculations with static structures.

PMID- 17172299
TI  - Forced unfolding of coiled-coils in fibrinogen by single-molecule AFM.
AB  - Fibrinogen is a blood plasma protein that, after activation by thrombin,
      assembles into fibrin fibers that form the elastic network of blood clots. We
      used atomic force microscopy to study the forced unfolding of engineered linear
      oligomers of fibrinogen, and we show that forced extension of the oligomers
      produces sawtooth patterns with a peak-to-peak length consistent with the
      independent unfolding of the coiled-coils in a cooperative two-state manner. In
      contrast with force plateaus seen for myosin coiled-coils that suggested rapid
      refolding of myosin, Monte Carlo simulations of fibrinogen unfolding confirm that
      fibrinogen refolding is negligible on experimental timescales. The distinct
      behavior of fibrinogen seems to be due to its topologically complex coiled-coils
      and an interaction between fibrinogen's alphaC-domains and its central region.

PMID- 17172298
TI  - Insights into correlated motions and long-range interactions in CheY derived from
      molecular dynamics simulations.
AB  - CheY is a response regulator protein involved in bacterial chemotaxis. Much is
      known about its active and inactive conformations, but little is known about the
      mechanisms underlying long-range interactions or correlated motions. To
      investigate these events, molecular dynamics simulations were performed on the
      unphosphorylated, inactive structure from Salmonella typhimurium and the CheY
      BeF(3)(-) active mimic structure (with BeF(3)(-) removed) from Escherichia coli.
      Simulations utilized both sequences in each conformation to discriminate sequence
      and structure-specific behavior. The previously identified conformational
      differences between the inactive and active conformations of the strand-4-helix-4
      loop, which are present in these simulations, arise from the structural, and not
      the sequence, differences. The simulations identify previously unreported
      structure-specific flexibility features in this loop and sequence-specific
      flexibility features in other regions of the protein. Both structure- and
      sequence-specific long-range interactions are observed in the active and inactive
      ensembles. In the inactive ensemble, two distinct mechanisms based on Thr-87 or
      Ile-95 rotameric forms, are observed for the previously identified g+ and g-
      rotamer sampling by Tyr-106. These molecular dynamics simulations have thus
      identified both sequence- and structure-specific differences in flexibility, long
      range interactions, and rotameric form of key residues. Potential biological
      consequences of differential flexibility and long-range correlated motion are
      discussed.

PMID- 17172300
TI  - Inferring the cellular origin of voltage and calcium alternans from the spatial
      scales of phase reversal during discordant alternans.
AB  - Beat-to-beat alternation of the action potential duration (APD) in paced cardiac
      cells has been linked to the onset of lethal arrhythmias. Both experimental and
      theoretical studies have shown that alternans at the single cell level can be
      caused by unstable membrane voltage (V(m)) dynamics linked to steep APD
      restitution, or unstable intracellular calcium (Ca) cycling linked to high
      sensitivity of Ca release from the sarcoplasmic reticulum on sarcoplasmic
      reticulum Ca load. Identifying which of these two mechanisms is the primary cause
      of cellular alternans, however, has remained difficult since Ca and V(m) are
      bidirectionally coupled. Here, we use numerical simulations of a physiologically
      detailed ionic model to show that the origin of alternans can be inferred by
      measuring the length scales over which APD and Ca(i) alternans reverse phase
      during spatially discordant alternans. The main conclusion is that these scales
      are comparable to a few millimeters and equal when alternans is driven by APD
      restitution, but differ markedly when alternans is driven predominantly by
      unstable Ca cycling. In the latter case, APD alternans still reverses phase on a
      millimeter tissue scale due to electrotonic coupling, while Ca alternans reverses
      phase on a submillimeter cellular scale. These results show that experimentally
      accessible measurements of Ca(i) and V(m) in cardiac tissue can be used to shed
      light on the cellular origin of alternans.

PMID- 17172301
TI  - Size distribution of linear and helical polymers in actin solution analyzed by
      photon counting histogram.
AB  - Actin is a ubiquitous protein that is a major component of the cytoskeleton,
      playing an important role in muscle contraction and cell motility. At steady
      state, actin monomers and filaments (F-actin) coexist, and actin subunits
      continuously attach and detach at the filament ends. However, the size
      distribution of actin oligomers in F-actin solution has never been clarified. In
      this study, we investigated the size distribution of actin oligomers using photon
      counting histograms. For this purpose, actin was labeled with a fluorescent dye,
      and the emitted photons were detected by confocal optics (the detection volume
      was of femtoliter (fL) order). Photon-counting histograms were analyzed to obtain
      the number distribution of actin oligomers in the detection area from their
      brightness, assuming that the brightness of an oligomer was proportional to the
      number of protomers. We found that the major populations at physiological ionic
      strength were 1-5mers. For data analysis, we successfully applied the theory of
      linear and helical aggregations of macromolecules. The model postulates three
      states of actin, i.e., monomers, linear polymers, and helical polymers. Here we
      obtained three parameters: the equilibrium constants for polymerization of linear
      polymers, K(l)=(5.2 +/- 1.1) x 10(6) M(-1), and helical polymers, K(h)=(1.6 +/-
      0.5) x 10(7) M(-1); and the ratio of helical to linear trimers, gamma = (3.6 +/-
      2.3) x 10(-2). The excess free energy of transforming a linear trimer to a
      helical trimer, which is assumed to be a nucleus for helical polymers, was
      calculated to be 2.0 kcal/mol. These analyses demonstrate that the oligomeric
      phase at steady state is predominantly composed of linear 1-5mers, and the
      transition from linear to helical polymers occurs on the level of 5-7mers.

PMID- 17172302
TI  - Hydrophobic, hydrophilic, and charged amino acid networks within protein.
AB  - The native three-dimensional structure of a single protein is determined by the
      physicochemical nature of its constituent amino acids. The 20 different types of
      amino acids, depending on their physicochemical properties, can be grouped into
      three major classes: hydrophobic, hydrophilic, and charged. The anatomy of the
      weighted and unweighted networks of hydrophobic, hydrophilic, and charged
      residues separately for a large number of proteins were studied. Results showed
      that the average degree of the hydrophobic networks has a significantly larger
      value than that of hydrophilic and charged networks. The average degree of the
      hydrophilic networks is slightly higher than that of the charged networks. The
      average strength of the nodes of hydrophobic networks is nearly equal to that of
      the charged network, whereas that of hydrophilic networks has a smaller value
      than that of hydrophobic and charged networks. The average strength for each of
      the three types of networks varies with its degree. The average strength of a
      node in a charged network increases more sharply than that of the hydrophobic and
      hydrophilic networks. Each of the three types of networks exhibits the "small
      world" property. Our results further indicate that the all-amino-acids networks
      and hydrophobic networks are of assortative type. Although most of the
      hydrophilic and charged networks are of the assortative type, few others have the
      characteristics of disassortative mixing of the nodes. We have further observed
      that all-amino-acids networks and hydrophobic networks bear the signature of
      hierarchy, whereas the hydrophilic and charged networks do not have any
      hierarchical signature.

PMID- 17172304
TI  - Biophysical studies of the c-MYC NHE III1 promoter: model quadruplex interactions
      with a cationic porphyrin.
AB  - Regulation of the structural equilibrium of G-quadruplex-forming sequences
      located in the promoter regions of oncogenes by the binding of small molecules
      has shown potential as a new avenue for cancer chemotherapy. In this study,
      microcalorimetry (isothermal titration calorimetry and differential scanning
      calorimetry), electronic spectroscopy (ultraviolet-visible and circular
      dichroism), and molecular modeling were used to probe the complex interactions
      between a cationic porphryin mesotetra (N-methyl-4-pyridyl) porphine (TMPyP4) and
      the c-MYC PU 27-mer quadruplex. The stoichiometry at saturation is 4:1 mol of
      TMPyP4/c-MYC PU 27-mer G-quadruplex as determined by isothermal titration
      calorimetry, circular dichroism, and ultraviolet-visible spectroscopy. The four
      independent TMPyP4 binding sites fall into one of two modes. The two binding
      modes are different with respect to affinity, enthalpy change, and entropy change
      for formation of the 1:1 and 2:1, or 3:1 and 4:1 complexes. Binding of TMPyP4, at
      or near physiologic ionic strength ([K(+)] = 0.13 M), is described by a "two
      independent-sites model." The two highest-affinity sites exhibit a K(1) of 1.6 x
      10(7) M(-1) and the two lowest-affinity sites exhibit a K(2) of 4.2 x 10(5) M(
      1). Dissection of the free-energy change into the enthalpy- and entropy-change
      contributions for the two modes is consistent with both "intercalative" and
      "exterior" binding mechanisms. An additional complexity is that there may be as
      many as six possible conformational quadruplex isomers based on the sequence.
      Differential scanning calorimetry experiments demonstrated two distinct melting
      events (T(m)1 = 74.7 degrees C and T(m)2 = 91.2 degrees C) resulting from a
      mixture of at least two conformers for the c-MYC PU 27-mer in solution.

PMID- 17172303
TI  - Noninvasive assessment of collagen gel microstructure and mechanics using
      multiphoton microscopy.
AB  - Multiphoton microscopy of collagen hydrogels produces second harmonic generation
      (SHG) and two-photon fluorescence (TPF) images, which can be used to
      noninvasively study gel microstructure at depth ( approximately 1 mm). The
      microstructure is also a primary determinate of the mechanical properties of the
      gel; thus, we hypothesized that bulk optical properties (i.e., SHG and TPF) could
      be used to predict bulk mechanical properties of collagen hydrogels. We utilized
      polymerization temperature (4-37 degrees C) and glutaraldehyde to manipulate
      collagen hydrogel fiber diameter, space-filling properties, and cross-link
      density. Multiphoton microscopy and scanning electron microscopy reveal that as
      polymerization temperature decreases (37-4 degrees C) fiber diameter and pore
      size increase, whereas hydrogel storage modulus (G', from 23 +/- 3 Pa to 0.28 +/-
      0.16 Pa, respectively, mean +/- SE) and mean SHG decrease (minimal change in
      TPF). In contrast, glutaraldehyde significantly increases the mean TPF signal
      (without impacting the SHG signal) and the storage modulus (16 +/- 3.5 Pa before
      to 138 +/- 40 Pa after cross-linking, mean +/- SD). We conclude that SHG and TPF
      can characterize differential microscopic features of the collagen hydrogel that
      are strongly correlated with bulk mechanical properties. Thus, optical imaging
      may be a useful noninvasive tool to assess tissue mechanics.

PMID- 17172305
TI  - Interaction of glycolysis and mitochondrial respiration in metabolic oscillations
      of pancreatic islets.
AB  - Insulin secretion from pancreatic beta-cells is oscillatory, with a typical
      period of 2-7 min, reflecting oscillations in membrane potential and the
      cytosolic Ca(2+) concentration. Our central hypothesis is that the slow 2-7 min
      oscillations are due to glycolytic oscillations, whereas faster oscillations that
      are superimposed are due to Ca(2+) feedback onto metabolism or ion channels. We
      extend a previous mathematical model based on this hypothesis to include a more
      detailed description of mitochondrial metabolism. We demonstrate that this model
      can account for typical oscillatory patterns of membrane potential and Ca(2+)
      concentration in islets. It also accounts for temporal data on oxygen consumption
      in islets. A recent challenge to the notion that glycolytic oscillations drive
      slow Ca(2+) oscillations in islets are data showing that oscillations in Ca(2+),
      mitochondrial oxygen consumption, and NAD(P)H levels are all terminated by
      membrane hyperpolarization. We demonstrate that these data are in fact compatible
      with a model in which glycolytic oscillations are the key player in rhythmic
      islet activity. Finally, we use the model to address the recent finding that the
      activity of islets from some mice is uniformly fast, whereas that from islets of
      other mice is slow. We propose a mechanism for this dichotomy.

PMID- 17172306
TI  - Enhanced fluorescence cell imaging with metal-coated slides.
AB  - Fluorescence labeling is the prevailing imaging technique in cell biology
      research. When they involve statistical investigations on a large number of
      cells, experimental studies require both low magnification to get a reliable
      statistical population and high contrast to achieve accurate diagnosis on the
      nature of the cells' perturbation. Because microscope objectives of low
      magnification generally yield low collection efficiency, such studies are limited
      by the fluorescence signal weakness. To overcome this technological bottleneck,
      we proposed a new method based on metal-coated substrates that enhance the
      fluorescence process and improve collection efficiency in epifluorescence
      observation and that can be directly used with a common microscope setup. We
      developed a model based on the dipole approximation with the aim of simulating
      the optical behavior of a fluorophore on such a substrate and revealing the
      different mechanisms responsible for fluorescence enhancement. The presence of a
      reflective surface modifies both excitation and emission processes and
      additionally reshapes fluorescence emission lobes. From both theoretical and
      experimental results, we found the fluorescence signal emitted by a molecular
      cyanine 3 dye layer to be amplified by a factor approximately 30 when
      fluorophores are separated by a proper distance from the substrate. We then
      adapted our model to the case of homogeneously stained micrometer-sized objects
      and demonstrated mean signal amplification by a factor approximately 4. Finally,
      we applied our method to fluorescence imaging of dog kidney cells and verified
      experimentally the simulated results.

PMID- 17172307
TI  - Ile-phe dipeptide self-assembly: clues to amyloid formation.
AB  - Peptidic self-assembled nanostructures are said to have a wide range of
      applications in nanotechnology, yet the mechanistic details of hierarchical self
      assembly are still poorly understood. The Phe-Phe recognition motif of the
      Alzheimer's Abeta peptide is the smallest peptide able to assemble into higher
      order structures. Here, we show that the Ile-Phe dipeptide analog is also able to
      self-associate in aqueous solution as a transparent, thermoreversible gel formed
      by a network of fibrillar nanostructures that exhibit strong birefringence upon
      Congo red binding. Besides, a second dipeptide Val-Phe, differing only in a
      methyl group from the former, is unable to self-assemble. The detailed analysis
      of the differential polymeric behavior of these closely related molecules
      provides insight into the forces triggering the first steps in self-assembly
      processes such as amyloid formation.

PMID- 17172308
TI  - Solution pH alters mechanical and electrical properties of phosphatidylcholine
      membranes: relation between interfacial electrostatics, intramembrane potential,
      and bending elasticity.
AB  - Solution pH affects numerous biological processes and some biological membranes
      are exposed to extreme pH environments. We utilized micropipette aspiration of
      giant unilamellar vesicles composed of 1-stearoyl-2-oleoyl-phosphatidylcholine to
      characterize the effect of solution pH (2-9) on membrane mechanical properties.
      The elastic area compressibility modulus was unaffected between pH 3 and 9 but
      was reduced by approximately 30% at pH 2. Fluorescence experiments utilizing the
      phase-sensitive probe Laurdan confirmed gel-phase characteristics at pH 2,
      explaining the reduction of membrane elasticity. The membrane bending stiffness,
      kc, increased by approximately 40% at pH 4 and pH 9 over the control value at pH
      6.5. Electrophoretic mobility measurements indicate that these changes are
      qualitatively consistent with theoretical models that predict the effect of
      membrane surface charge density and Debye length on kc, substantiating a coupling
      between the mechanical and interfacial electrical properties of the membrane. The
      effect of pH on intramembrane electrical properties was examined by studying the
      spectral shifts of the potentiometric probe di-8 ANEPPS. The intramembrane
      (dipole) potential (Psid) increased linearly as the solution pH decreased in a
      manner consistent with the partitioning of hydroxide ions into the membrane.
      However, changes in Psid did not correlate with changes in kc. These mechanical
      and electrical studies lead to the conclusion that the effect of pH on membrane
      bending stiffness results from alterations in interfacial, as opposed to
      intramembrane, electrostatics.

PMID- 17172309
TI  - Force-extension measurements on bacterial flagella: triggering polymorphic
      transformations.
AB  - Bacterial flagella can adopt several different helical shapes in response to
      varying environmental conditions. A geometric model by Calladine ascribes these
      discrete shape changes to cooperative transitions between two stable tertiary
      structures of the constituent protein, flagellin, and predicts an ordered set of
      12 helical states called polymorphic forms. Using long polymers of purified
      flagellin, we demonstrate controlled, reversible transformations between
      different polymorphic forms. While pulling on a single filament using an optical
      tweezer, we record the progressive transformation of the filament and also
      measure the force-extension curve. Both normal and coiled polymorphic forms
      stretch elastically with a bending stiffness of 3.5 pN x microm(2). At a force
      threshold of 4-7 pN or 3-5 pN (for normal and coiled forms, respectively), a
      fraction of the filament suddenly transforms to the next, longer, polymorphic
      form. This transformation is not deterministic because the force and amount of
      transformation vary from pull to pull. In addition, the force is highly dependent
      on stretching rate, suggesting that polymorphic transformation is associated with
      an activation energy.

PMID- 17172310
TI  - Thermodynamics-based metabolic flux analysis.
AB  - A new form of metabolic flux analysis (MFA) called thermodynamics-based metabolic
      flux analysis (TMFA) is introduced with the capability of generating
      thermodynamically feasible flux and metabolite activity profiles on a genome
      scale. TMFA involves the use of a set of linear thermodynamic constraints in
      addition to the mass balance constraints typically used in MFA. TMFA produces
      flux distributions that do not contain any thermodynamically infeasible reactions
      or pathways, and it provides information about the free energy change of
      reactions and the range of metabolite activities in addition to reaction fluxes.
      TMFA is applied to study the thermodynamically feasible ranges for the fluxes and
      the Gibbs free energy change, Delta(r)G', of the reactions and the activities of
      the metabolites in the genome-scale metabolic model of Escherichia coli developed
      by Palsson and co-workers. In the TMFA of the genome scale model, the metabolite
      activities and reaction Delta(r)G' are able to achieve a wide range of values at
      optimal growth. The reaction dihydroorotase is identified as a possible
      thermodynamic bottleneck in E. coli metabolism with a Delta(r)G' constrained
      close to zero while numerous reactions are identified throughout metabolism for
      which Delta(r)G' is always highly negative regardless of metabolite
      concentrations. As it has been proposed previously, these reactions with
      exclusively negative Delta(r)G' might be candidates for cell regulation, and we
      find that a significant number of these reactions appear to be the first steps in
      the linear portion of numerous biosynthesis pathways. The thermodynamically
      feasible ranges for the concentration ratios ATP/ADP, NAD(P)/NAD(P)H, and
      H(extracellular)(+)/H(intracellular)(+) are also determined and found to
      encompass the values observed experimentally in every case. Further, we find that
      the NAD/NADH and NADP/NADPH ratios maintained in the cell are close to the
      minimum feasible ratio and maximum feasible ratio, respectively.

PMID- 17172311
TI  - Inhibition of MRP1/ABCC1, MRP2/ABCC2, and MRP3/ABCC3 by nucleoside, nucleotide,
      and non-nucleoside reverse transcriptase inhibitors.
AB  - Many drug interactions with drugs used for the therapy of human immunodeficiency
      virus (HIV) occur at the level of different cytochrome P450 isozymes. Increasing
      evidence suggests that antiretrovirals may also modify activity and expression of
      active drug transport systems. Such interactions may alter drug absorption,
      elimination, and also drug distribution and reach clinical importance if thereby
      access to the target site is affected. Beyond P-glycoprotein, the family of
      multidrug resistance-related proteins (MRP/ABCC) substantially contributes to the
      elimination of numerous drugs and their metabolites. Because the interaction of
      MRPs with non-HIV protease inhibitor antiretrovirals has not been studied
      thoroughly, we investigated whether important non-nucleoside reverse
      transcriptase inhibitors (NNRTI) (delavirdine, efavirenz, and nevirapine),
      nucleoside reverse transcriptase inhibitors (NRTI) (abacavir, emtricitabine, and
      lamivudine), and tenofovir as a nonnucleotide reverse transcriptase inhibitor can
      interact with MRP1, MRP2, and MRP3 in vitro. Inhibition of these ABC transporters
      was quantified by confocal laser-scanning microscopy using the 5
      chloromethylfluorescein diacetate assay. With the exception of abacavir, which
      had no effect on MRP3, all the test compounds increased intracellular 5
      chloromethylfluorescein fluorescence in a concentration-dependent manner, and
      this effect was observed in all the overexpressing cell lines but not in the
      parental cell line, indicating inhibition of MRP1, MRP2, and MRP3. In conclusion,
      the present study provides the first evidence for a significant and concentration
      dependent inhibition of MRPs by NNRTI, NRTI, and tenofovir, which was most
      pronounced for delavirdine, efavirenz, and emtricitabine, suggesting that this
      might contribute to some of the known drug interactions impairing HIV therapy and
      also to the superior effectiveness of combination pharmacotherapy.

PMID- 17172312
TI  - Cross-species pharmacokinetic comparison from mouse to man of a second-generation
      antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100.
AB  - The pharmacokinetics of a 2'-O-(2-methoxyethyl)-modified oligonucleotide, ISIS
      301012 [targeting human apolipoprotein B-100 (apoB-100)], was characterized in
      mouse, rat, monkey, and human. Plasma pharmacokinetics following parental
      administration was similar across species, exhibiting a rapid distribution phase
      with t(1/2alpha) of several hours and a prolonged elimination phase with
      t(1/2beta) of days. The prolonged elimination phase represents equilibrium
      between tissues and circulating drug due to slow elimination from tissues.
      Absorption was nearly complete following s.c. injection, with bioavailability
      ranging from 80 to 100% in monkeys. Plasma clearance scaled well across species
      as a function of body weight alone, and this correlation was improved when
      corrected for plasma protein binding. In all of the animal models studied, the
      highest tissue concentrations of ISIS 301012 were observed in kidney and liver.
      Urinary excretion was less than 3% in monkeys and human in the first 24 h. ISIS
      301012 is highly bound to plasma proteins, probably preventing rapid removal by
      renal filtration. However, following 25 mg/kg s.c. administration in mouse and 5
      mg/kg i.v. bolus administration in rat, plasma concentrations of ISIS 301012
      exceeded their respective protein binding capacity. Thus, urinary excretion
      increased to 16% or greater within the first 24 h. Albeit slow, urinary excretion
      of ISIS 301012 and its shortened metabolites is the ultimate elimination pathway
      of this compound, as demonstrated by 32% of dose recovered in total excreta by 14
      days in a rat mass balance study. The pharmacokinetics of ISIS 301012 in human is
      predictable from the pharmacokinetics measured in animals. The pharmacokinetic
      properties of ISIS 301012 provide guidance for clinical development and support
      infrequent dose administration.

PMID- 17172313
TI  - Gender-related differences in mycophenolate mofetil-induced gastrointestinal
      toxicity in rats.
AB  - Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is included
      in current combination immunosuppressive regimens following organ transplant.
      Treatment with MMF often results in dose-limiting gastrointestinal (GI) side
      effects. The underlying mechanisms responsible for these side effects are not
      fully understood, but exposure of the intestinal epithelia to MPA during
      enterohepatic recycling may be involved. The present study demonstrated that
      female rats are more susceptible to MMF-induced GI toxicity than male rats.
      Female Sprague-Dawley rats treated chronically with an oral dose of 50 mg of MPA
      equivalents/kg/day experienced greater GI toxicity than male rats, as measured by
      diarrhea grade and weight loss. Intestinal microsomes harvested from the upper
      jejunum of female rats had approximately 3-fold lower MPA glucuronidation rates
      compared with male rats. In the remaining areas of the small and large intestine,
      there was also a trend toward decreased glucuronidation in the female rats. The
      area under the plasma concentration-time curve (AUC) for MPA following an oral
      dose of 50 mg of MPA equivalents/kg was roughly similar between genders, whereas
      the AUC for mycophenolic acid phenolic glucuronide (MPAG) was significantly lower
      in female rats. Female rats also excreted half of the biliary MPAG as male rats.
      The greater susceptibility of female rats to MMF-induced gastrointestinal
      toxicity, despite diminished intestinal MPA exposure via reduced biliary
      excretion of MPAG, may result from reduced protection of enterocytes by in situ
      glucuronidation. Likewise, susceptibility to MMF-induced GI toxicity in humans
      may also result from variable intestinal glucuronidation due to UDP
      glucuronosyltransferase polymorphisms or differential expression.

PMID- 17172314
TI  - Inhibitory effects of benzoate on chiral inversion and clearance of N(G)-nitro
      arginine in conscious rats.
AB  - N(G)-nitro-arginine (NNA) is known to exhibit stereoselective pharmacokinetics in
      which N(G)-nitro-d-arginine (d-NNA) has a faster clearance rate than N(G)-nitro-l
      arginine (l-NNA) in anesthetized rats, and d-NNA undergoes unidirectional chiral
      inversion. It was postulated that chiral inversion of d-NNA was performed in a
      two-step pathway by d-amino acid oxidase (DAAO) followed by an unidentified
      transaminase. Such chiral inversion contributes (at least partially) to the
      pharmacokinetic stereoselectivity of NNA. This study used the selective inhibitor
      of DAAO, sodium benzoate, to test the above hypothesis. An i.v. bolus injection
      of d-NNA (32 mg/kg) and l-NNA (16 mg/kg) in conscious rats exhibited biphasic
      disposition with different pharmacokinetic parameters in a stereospecific manner
      (approximately 5-10-fold differences). Unidirectional chiral inversion of d-NNA
      but not l-NNA was found from these animals. In addition to its similar inhibitory
      effects on the d-NNA conversion and DAAO activity in kidney homogenates, sodium
      benzoate completely blocked chiral inversion of d-NNA and led to a smaller
      stereospecific difference, reflected by a nearly 50% reduction of d-NNA clearance
      and a 2-fold increase in t(1/2) and area under the curve of d-NNA in benzoate
      pretreated rats. The results suggest that DAAO plays an essential role in chiral
      inversion of d-NNA and chiral inversion contributes mostly to the pharmacokinetic
      stereospecificity of NNA.

PMID- 17172315
TI  - Specializations of a G-protein-coupled receptor that appear to aid with detection
      of frequency-modulated signals from its ligand.
AB  - The primate GnRH receptor (GnRHR) is a GPCR (G-protein-coupled receptor) that
      transduces both amplitude- and frequency-modulated signals; each modality conveys
      information that regulates primate reproduction. Slower GnRH pulses favor release
      (and higher circulating levels) of pituitary FSH, while faster pulses favor LH
      release. We used radioligand binding and inositol phosphate production (a measure
      of G-protein coupling) in association with mutational analysis to identify the
      impact of evolved sequence specializations that regulate receptor concentration
      at the plasma membrane and Kd in primate GnRHRs. Our results show that mutations
      appear to provide a mechanism that allows independent adjustment of response
      sensitivity and squelching (suppression) of low-level signals (noise), both
      desirable features for recognition of frequency-modulated signals. We identify
      specific amino acid residues that appear to be involved in these processes. This
      investigation occurred in light of recent observations that restriction of GnRHR
      plasma membrane expression developed under strong convergent pressure and
      concurrently with the complex pattern of cyclicity associated with primate
      reproduction. The findings present an evolved means for increased effectiveness
      of detection of a frequency-modulated signal and provide a strategy to identify
      similar mechanisms in other receptors.

PMID- 17172316
TI  - Effects of high-intensity endurance and resistance exercise on HIV metabolic
      abnormalities: a pilot study.
AB  - The purposes of this pilot study were to examine the effects of a 16-week
      supervised high-intensity combined endurance and resistance exercise training
      program on HIV-associated metabolic abnormalities (abdominal adiposity,
      dyslipidemia, and insulin resistance) and to explore methodological issues
      related to the design and implementation of the research protocol in preparation
      for a randomized controlled trial. A one-group pretest-posttest design was used,
      with outcomes measured at baseline and within 1 week after the conclusion of the
      training program. The exercise program consisted of 16 weeks (preceded by a 2
      week phase-in period) of three endurance sessions (20 min at 70%-80% of VO
      (2max)) and two resistance sessions per week (one set of 8-10 repetitions at 80%
      of one-repetition maximum on seven exercises). Outcome measures included lipid
      levels (total, high-density lipoprotein, and low-density lipoprotein cholesterol
      and triglycerides), visceral and subcutaneous adipose area measured by electron
      beam tomography, fat and lean mass of trunk and limbs measured by dual-energy X
      ray absorptiometry, and insulin sensitivity measured by the homeostatic model
      assessment. Nine participants were recruited, 5 of whom completed the
      intervention and had pretest and posttest data available for analyses. Aerobic
      capacity and strength improved over the course of the intervention. Statistically
      significant decreases were found for total and trunk fat mass (1,324.9 g [+/
      733.6] and 992.8 g [+/-733.6], respectively). Triglycerides decreased by 59 mg/dL
      (+/-69.88), and insulin sensitivity decreased by 15.7% (+/-41.7%), neither of
      which was a statistically significant change. Results suggest that further
      testing of the combined exercise intervention in a randomized controlled design
      is warranted.

PMID- 17172317
TI  - The effects of exercise on perceived stress and IL-6 levels among older adults.
AB  - Biochemical markers of inflammation have been used in recent physical activity
      intervention studies. However, these same biochemical markers, mainly
      proinflammatory cytokines, may also be influenced by the individual's level of
      stress and mood. Accordingly, this pilot study was implemented to determine the
      effect of a physical activity intervention on perceived stress, mood, quality of
      life, serum interleukin-6 (IL-6), and cortisol among 10 older adults, age 60 to
      90. The results were compared to those of 10 older adults who were not engaging
      in regular physical activity. The 10-week intervention was applied using student
      nurses who taught the older adults how to calculate 60% of their maximum heart
      rate while ambulating for 30-min intervals. After the 10-week period, the
      participants in the exercise group reported significant improvements in stress,
      mood, and several quality of life indices. They also demonstrated a significant
      decrease in serum IL-6. Stress, mood, and quality of life scores in the exercise
      group were also significantly improved compared to the control group. This study
      adds information on the specific intensity, duration, and frequency of exercise
      necessary to achieve improvements in psychological variables and IL-6 levels. It
      also supports the need to measure psychological stress in physical activity
      intervention studies. Although the psychological variables were highly
      correlated, there were only weak correlations found with IL-6, suggesting that
      other factors are likely involved in reducing IL-6 when engaging in low-impact
      physical activity.

PMID- 17172318
TI  - Waterproofing EMG Instrumentation.
AB  - While still experimental, measurement of external uterine electromyographic (EMG)
      activity is a more sensitive and noninvasive method for measuring uterine
      contractility in human labor than the methods currently used in clinical
      practice. Hydrotherapy is purported to improve contractility in labor, yet there
      have been no reports of abdominal uterine EMG activity measured during immersion.
      To test telemetric EMG equipment and different waterproofing techniques under dry
      and immersed conditions, the authors recorded surface EMG activity from the
      abdominal muscles of 11 healthy, nonpregnant women, 22 to 51 years of age. After
      attaching one pair of electrodes to the skin on either side of the umbilicus and
      applying the waterproofing material, the authors tested the signal by asking
      participants to perform a short series of leg lifts while seated in a chair to
      evoke abdominal muscle contractions. They were then immersed to the chest in a
      hydrotherapy tub while performing two to three leg lifts over 60 s every 5 min
      for 60 min with 20 lb of weight suspended from their ankles to counteract the
      buoyancy effect of water. EMG activity was continuously recorded. They then
      repeated the dry-measures sequence. While waterproofing remained intact, EMG
      signals were essentially unchanged between dry and wet conditions. Of the 11
      waterproofing applications tested, 10 failed at some point. In the data from the
      successful application, EMG signals in both channels exhibited stable baselines
      throughout and an absence of low-frequency artifact. The development of this
      technique allows for the recording of external uterine EMG activity during
      hydrotherapy. The authors have begun using it to investigate the effects of
      hydrotherapy on uterine contractility during human labor.

PMID- 17172319
TI  - Subglottic secretion viscosity and evacuation efficiency.
AB  - Ventilator-associated pneumonia (VAP) is a common nosocomial pneumonia that
      occurs in critically ill patients and results in mortality rates as high as 71%.
      Subglottic secretions (SSs) are a known risk factor. Several clinical trials have
      shown that continuous aspiration of subglottic secretions (CASS) reduces the risk
      of VAP by nearly half. Optimal suction pressure levels needed to efficiently
      evacuate viscous SSs are unknown. The purpose of this study was to describe SSs
      and the effective suction pressure (20 mmHg, 30 mmHg, 40 mmHg, and 50 mmHg)
      needed to maximize evacuation efficiency based on SS volume (2 ml, 4 ml, and 6
      ml) and viscosity (watery, thick, and gel-like). A laboratory model was designed
      to replicate a human trachea. Thick secretions had the highest percentage of mean
      recovery representative of evacuation efficiency of SSs (mean recovery of 86%).
      The suction pressure of 30 mmHg had the highest overall mean of secretion
      recovery (83%) across all viscosity types and amounts. This study demonstrated
      that higher viscosity secretions were easier to evacuate than lower viscosity
      secretions when 30-mmHg suction pressure was applied. Management of secretion
      viscosity may assist in secretion removal and delay VAP development. With
      increased understanding of the molecular structure of SSs, there is the potential
      that clinicians will be able to manipulate secretion viscoelastic properties to
      maximize evacuation efficiency of the secretions. Further research is needed to
      identify safe suction pressures for optimal evacuation of SSs in human subjects.

PMID- 17172320
TI  - Dysregulation of the hypothalamic-pituitary-adrenal axis in postpartum
      depression.
AB  - Postpartum depression (PPD) affects at least 10% to 15% of postpartum women,
      including more than 600,000 American mothers in 2003 alone. Dramatic changes in
      the hypothalamic-pituitary-adrenal (HPA) system in the transition from pregnancy
      to postpartum coupled with research on the psychobiology of depression provided
      the foundation for this study. The purpose of this study was to compare the
      reactivity and regulation of the HPA axis components, adrenocorticotropic hormone
      (ACTH) and cortisol, in depressed and nondepressed postpartum women. A
      comparative, longitudinal study design was used with 22 normal, healthy,
      nondepressed pregnant women. Physiologic and postpartum depression data were
      collected at 6 and 12 weeks postpartum at a university clinical research center.
      Maximal treadmill exercise stimulated plasma ACTH and serum cortisol levels which
      were measured before, during, and after 20 min of exercise. Postpartum depression
      was measured with the Postpartum Depression Screening Scale. Lag within-subject
      ACTH levels predicting cortisol regression slopes were significantly different
      between the depressed and nondepressed groups at both 6 and 12 weeks. The
      depressed group showed no relationship between their ACTH and cortisol levels,
      with higher ACTH and lower cortisol levels when compared with the nondepressed
      group. The expected regulated relationship with cortisol levels rising in
      response to rising ACTH levels was found in the non-depressed group. These
      findings indicate that the HPA axis was dysregulated in the depressed group, but
      regulated in the nondepressed group at 6 and 12 weeks postpartum. This pattern of
      higher ACTH levels to stimulate less cortisol is similar to patterns found in
      women with early life stresses.

PMID- 17172321
TI  - Promising new causal explanations for obesity and obesity-related diseases.
AB  - Current explanations for obesity center around a predisposition in genotype and
      phenotype, possibly triggered by an inflammatory process or event, and
      exacerbated by environmental and psychological factors. It is likely that a
      variety of physiologic factors may act in combination to produce clinical
      obesity. Leptin resistance may be an important neurochemical cause of obesity;
      elevated leptin levels have been correlated with weight gain over extended time
      periods. Genetic studies support the postulate that a gene originating with our
      cave-dwelling ancestors, critical to survival when food was scare, has evolved
      into a trigger for obesity and related diseases. A variety of biochemical markers
      are prevalent in obesity and obesity-linked disease states. C-reactive protein,
      interleukin-6, and others are elevated in obesity, supporting the hypothesis that
      inflammation plays a role in the condition. Tumor necrosis factor-alpha is
      overexpressed in obesity and diabetes, suggesting that it may be part of the link
      between the 2 conditions.

PMID- 17172322
TI  - Antinociceptive effects of the aqueous extract of Brugmansia suaveolens flowers
      in mice.
AB  - The infusion of Brugmansia suaveolens, popularly known as trombeteira or
      cartucheira, has been used to treat pain in Brazil. The present study was
      conducted to test for its antinociceptive effects using the abdominal-writhing,
      formalin, tail-flick, and hot-plate tests in mice. The aqueous extract from B.
      suaveolens flowers administered intraperitoneally at doses of 100 and 300 mg/kg
      body weight significantly inhibited acetic acid-induced abdominal constrictions.
      An increase in hot-plate latency was also observed in animals receiving both
      doses (100 and 300 mg/kg). In the formalin test, both doses from the aqueous
      extract inhibited the first (0-5 min) and second phase (20-25 min). Tail-flick
      assays demonstrated that treatment of animals with plant extract induced
      attenuation of the response. These results suggest that the aqueous extract from
      B. suaveolens flowers produced antinociceptive effects, as demonstrated in the
      experimental models of nociception in mice. This supports popular medicinal uses
      of this plant as an analgesic.

PMID- 17172323
TI  - Genome analyses of three strains of Rhodobacter sphaeroides: evidence of rapid
      evolution of chromosome II.
AB  - Three strains of Rhodobacter sphaeroides of diverse origin have been under
      investigation in our laboratory for their genome complexities, including the
      presence of multiple chromosomes and the distribution of essential genes within
      their genomes. The genome of R. sphaeroides 2.4.1 has been completely sequenced
      and fully annotated, and now two additional strains (ATCC 17019 and ATCC 17025)
      of R. sphaeroides have been sequenced. Thus, genome comparisons have become a
      useful approach in determining the evolutionary relationships among different
      strains of R. sphaeroides. In this study, the concatenated chromosomal sequences
      from the three strains of R. sphaeroides were aligned, using Mauve, to examine
      the extent of shared DNA regions and the degree of relatedness among their
      chromosome-specific DNA sequences. In addition, the exact intra- and
      interchromosomal DNA duplications were analyzed using Mummer. Genome analyses
      employing these two independent approaches revealed that strain ATCC 17025
      diverged considerably from the other two strains, 2.4.1 and ATCC 17029, and that
      the two latter strains are more closely related to one another. Results further
      demonstrated that chromosome II (CII)-specific DNA sequences of R. sphaeroides
      have rapidly evolved, while CI-specific DNA sequences have remained highly
      conserved. Aside from the size variation of CII of R. sphaeroides, variation in
      sequence lengths of the CII-shared DNA regions and their high sequence divergence
      among strains of R. sphaeroides suggest the involvement of CII in the evolution
      of strain-specific genomic rearrangements, perhaps requiring strains to adapt in
      specialized niches.

PMID- 17172324
TI  - Characterization of the transcriptional activity of the cryptic plasmid pRN1 from
      Sulfolobus islandicus REN1H1 and regulation of its replication operon.
AB  - The plasmid pRN1 from Sulfolobus islandicus REN1H1 belongs to the crenarchaeal
      plasmid family pRN. The plasmids in this family encode three conserved proteins
      that participate in plasmid replication and copy number regulation, as suggested
      by biochemical characterization of the recombinant proteins. In order to deepen
      our understanding of the molecular biology of these plasmids, we investigated the
      transcriptional activity of the model plasmid pRN1. We detected five major
      transcripts present at about 2 to 15 copies per cell. One long transcriptional
      unit comprises the genes for the plasmid-copy-number control protein Orf56/CopG
      and the replication protein Orf904. A second transcript with a long 3'
      untranslated region codes for the DNA binding protein Orf80. For both
      transcripts, we identified countertranscripts which could play a regulatory role.
      The function of the fifth transcript is unclear. For the five transcripts, we
      determined the start site, the transcript end, the stability, and the abundance
      in different growth phases. Reporter gene experiments demonstrated that the copy
      number control protein Orf56 represses transcription of the orf56-orf904
      cotranscript in vivo.

PMID- 17172325
TI  - Functional analysis of PilT from the toxic cyanobacterium Microcystis aeruginosa
      PCC 7806.
AB  - The evolution of the microcystin toxin gene cluster in phylogenetically distant
      cyanobacteria has been attributed to recombination, inactivation, and deletion
      events, although gene transfer may also be involved. Since the microcystin
      producing Microcystis aeruginosa PCC 7806 is naturally transformable, we have
      initiated the characterization of its type IV pilus system, involved in DNA
      uptake in many bacteria, to provide a physiological focus for the influence of
      gene transfer in microcystin evolution. The type IV pilus genes pilA, pilB, pilC,
      and pilT were shown to be expressed in M. aeruginosa PCC 7806. The purified PilT
      protein yielded a maximal ATPase activity of 37.5 +/- 1.8 nmol P(i) min(-1) mg
      protein(-1), with a requirement for Mg(2+). Heterologous expression indicated
      that it could complement the pilT mutant of Pseudomonas aeruginosa, but not that
      of the cyanobacterium Synechocystis sp. strain PCC 6803, which was unexpected.
      Differences in two critical residues between the M. aeruginosa PCC 7806 PilT
      (7806 PilT) and the Synechocystis sp. strain PCC 6803 PilT proteins affected
      their theoretical structural models, which may explain the nonfunctionality of
      7806 PilT in its cyanobacterial counterpart. Screening of the pilT gene in toxic
      and nontoxic strains of Microcystis was also performed.

PMID- 17172326
TI  - Identification of novel Sinorhizobium meliloti mutants compromised for oxidative
      stress protection and symbiosis.
AB  - Employing a novel two-part screen, we identified Sinorhizobium meliloti mutants
      that were both sensitive to hydrogen peroxide and symbiotically defective on the
      host plant Medicago sativa. The mutations affect a wide variety of cellular
      processes and represent both novel and previously identified genes important in
      symbiosis.

PMID- 17172328
TI  - The L-tartrate/succinate antiporter TtdT (YgjE) of L-tartrate fermentation in
      Escherichia coli.
AB  - Escherichia coli ferments L-tartrate under anaerobic conditions in the presence
      of an additional electron donor to succinate. The carrier for L-tartrate uptake
      and succinate export and its relation to the general C(4)-dicarboxylate carriers
      DcuA, DcuB, and DcuC were studied. The secondary carrier TtdT, encoded by the
      ttdT (previously called ygjE) gene, is required for the uptake of L-tartrate. The
      ttdT gene is located downstream of the ttdA and ttdB genes, encoding the L
      tartrate dehydratase TtdAB. Analysis of mRNA by reverse transcription-PCR showed
      that ttdA, ttdB, and ttdT are cotranscribed. Deletion of ttdT abolished growth by
      L-tartrate and degradation of L-tartrate completely. Bacteria containing TtdT
      catalyze L-tartrate or succinate uptake and specific heterologous L
      tartrate/succinate antiporting. D-Tartrate is not a substrate for TtdT. TtdT
      operates preferentially in the direction of tartrate uptake and succinate
      excretion. The Dcu carriers do not support anaerobic growth on L-tartrate or L
      tartrate transport. TtdT is related in sequence and function to CitT, which
      catalyzes heterologous citrate/succinate antiporting in citrate fermentation.

PMID- 17172327
TI  - A suppressor of cell death caused by the loss of sigmaE downregulates
      extracytoplasmic stress responses and outer membrane vesicle production in
      Escherichia coli.
AB  - When envelope biogenesis is compromised or damage to envelope components occurs,
      bacteria trigger signaling cascades, which lead to the production of proteins
      that combat such extracytoplasmic stresses. In Escherichia coli, there are three
      pathways known to deal with envelope stresses: the Bae, Cpx, and sigma(E)
      responses. Although the effectors of the Bae and Cpx responses are not essential
      in E. coli, the effector of the sigma(E) response, the sigma factor RpoE
      (sigma(E)), is essential for viability. However, mutations that suppress the
      lethality of an rpoE-null allele can be easily obtained, and here we describe how
      we have isolated at least four classes of these suppressors. We present the first
      description of one such suppressor class, loss-of-function mutations in ydcQ, a
      gene encoding a putative DNA-binding protein. In wild-type rpoE(+) strains, ydcQ
      mutants have two distinct phenotypes: extracytoplasmic stress responses are
      significantly downregulated, and the production of outer membrane vesicles is
      severely reduced. We present a model in which sigma(E) is not essential per se
      but, rather, we propose that rpoE mutant cells die, possibly because they
      overreact to the absence of this sigma factor by triggering a cell death signal.

PMID- 17172330
TI  - Rare group I intron with insertion sequence element in a bacterial ribonucleotide
      reductase gene.
AB  - A rare group I intron in a cyanobacterial ribonucleotide reductase gene has been
      characterized. It contains a mobile insertion sequence element not required for
      RNA splicing. Ribonucleotide reductase genes were found to be hot spots for all
      three types of self-splicing intervening sequences, including group I and II
      introns and inteins.

PMID- 17172329
TI  - Complete genome sequence of Haemophilus somnus (Histophilus somni) strain 129Pt
      and comparison to Haemophilus ducreyi 35000HP and Haemophilus influenzae Rd.
AB  - Haemophilus somnus can be either a commensal of bovine mucosal surfaces or an
      opportunistic pathogen. Pathogenic strains of H. somnus are a significant cause
      of systemic disease in cattle. We report the genome sequence of H. somnus 129Pt,
      a nonpathogenic commensal preputial isolate, and the results of a genome-wide
      comparative analysis of H. somnus 129Pt, Haemophilus influenzae Rd, and
      Haemophilus ducreyi 35000HP. We found unique genes in H. somnus 129Pt involved in
      lipooligosaccharide biosynthesis, carbohydrate uptake and metabolism, cation
      transport, amino acid metabolism, ubiquinone and menaquinone biosynthesis, cell
      surface adhesion, biosynthesis of cofactors, energy metabolism, and electron
      transport. There were also many genes in common among the three organisms. Our
      comparative analyses of H. somnus 129Pt, H. influenzae Rd, and H. ducreyi 35000HP
      revealed similarities and differences in the numbers and compositions of genes
      involved in metabolism, host colonization, and persistence. These results lay a
      foundation for research on the host specificities and niche preferences of these
      organisms. Future comparisons between H. somnus 129Pt and virulent strains will
      aid in the development of protective strategies and vaccines to protect cattle
      against H. somnus disease.

PMID- 17172331
TI  - CapA, an autotransporter protein of Campylobacter jejuni, mediates association
      with human epithelial cells and colonization of the chicken gut.
AB  - Two putative autotransporter proteins, CapA and CapB, were identified in silico
      from the genome sequence of Campylobacter jejuni NCTC11168. The genes encoding
      each protein contain homopolymeric tracts, suggestive of phase variation mediated
      by a slipped-strand mispairing mechanism; in each case the gene sequence
      contained frameshifts at these positions. The C-terminal two-thirds of the two
      genes, as well as a portion of the predicted signal peptides, were identical; the
      remaining N-terminal portions were gene specific. Both genes were cloned and
      expressed; recombinant polypeptides were purified and used to raise rabbit
      polyclonal monospecific antisera. Using immunoblotting, expression of the ca.116
      kDa CapA protein was demonstrated for in vitro-grown cells of strain NCTC11168,
      for 4 out of 11 recent human fecal isolates, and for 2 out of 8 sequence-typed
      strains examined. Expression of CapB was not detected for any of the strains
      tested. Surface localization of CapA was demonstrated by subcellular
      fractionation and immunogold electron microscopy. Export of CapA was inhibited by
      globomycin, reinforcing the bioinformatic prediction that the protein is a
      lipoprotein. A capA insertion mutant had a significantly reduced capacity for
      association with and invasion of Caco-2 cells and failed to colonize and persist
      in chickens, indicating that CapA plays a role in host association and
      colonization by Campylobacter. In view of this demonstrated role, we propose that
      CapA stands for Campylobacter adhesion protein A.

PMID- 17172332
TI  - Identification of IspC, an 86-kilodalton protein target of humoral immune
      response to infection with Listeria monocytogenes serotype 4b, as a novel surface
      autolysin.
AB  - We identified and biochemically characterized a novel surface-localized autolysin
      from Listeria monocytogenes serotype 4b, an 86-kDa protein consisting of 774
      amino acids and known from our previous studies as the target (designated IspC)
      of the humoral immune response to listerial infection. Recombinant IspC,
      expressed in Escherichia coli, was purified and used to raise specific rabbit
      polyclonal antibodies for protein characterization. The native IspC was detected
      in all growth phases at a relatively stable low level during a 22-h in vitro
      culture, although its gene was transiently transcribed only in the early
      exponential growth phase. This and our previous findings suggest that IspC is
      upregulated in vivo during infection. The protein was unevenly distributed in
      clusters on the cell surface, as shown by immunofluorescence and immunogold
      electron microscopy. The recombinant IspC was capable of hydrolyzing not only the
      cell walls of the gram-positive bacterium Micrococcus lysodeikticus and the gram
      negative bacterium E. coli but also that of the IspC-producing strain of L.
      monocytogenes serotype 4b, indicating that it was an autolysin. The IspC
      autolysin exhibited peptidoglycan hydrolase activity over a broad pH range of
      between 3 and 9, with a pH optimum of 7.5 to 9. Analysis of various truncated
      forms of IspC for cell wall-hydrolyzing or -binding activity has defined two
      separate functional domains: the N-terminal catalytic domain (amino acids [aa] 1
      to 197) responsible for the hydrolytic activity and the C-terminal domain (aa 198
      to 774) made up of seven GW modules responsible for anchoring the protein to the
      cell wall. In contrast to the full-length IspC, the N-terminal catalytic domain
      showed hydrolytic activity at acidic pHs, with a pH optimum of between 4 and 6
      and negligible activity at alkaline pHs. This suggests that the cell wall binding
      domain may be of importance in modulating the activity of the N-terminal
      hydrolase domain. Elucidation of the biochemical properties of IspC may have
      provided new insights into its biological function(s) and its role in
      pathogenesis.

PMID- 17172333
TI  - Genetic analysis of a novel pathway for D-xylose metabolism in Caulobacter
      crescentus.
AB  - Genetic data suggest that the oligotrophic freshwater bacterium Caulobacter
      crescentus metabolizes D-xylose through a pathway yielding alpha-ketoglutarate,
      comparable to the recently described L-arabinose degradation pathway of
      Azospirillum brasilense. Enzymes of the C. crescentus pathway, including an
      NAD(+)-dependent xylose dehydrogenase, are encoded in the xylose-inducible
      xylXABCD operon (CC0823-CC0819).

PMID- 17172334
TI  - Porin activity of Anaplasma phagocytophilum outer membrane fraction and purified
      P44.
AB  - Anaplasma phagocytophilum, an obligatory intracellular bacterium that causes
      human granulocytic anaplasmosis, has significantly less coding capacity for
      biosynthesis and central intermediary metabolism than do free-living bacteria.
      Thus, A. phagocytophilum needs to usurp and acquire various compounds from its
      host. Here we demonstrate that the isolated outer membrane of A. phagocytophilum
      has porin activity, as measured by a liposome swelling assay. The activity allows
      the diffusion of L-glutamine, the monosaccharides arabinose and glucose, the
      disaccharide sucrose, and even the tetrasaccharide stachyose, and this diffusion
      could be inhibited with an anti-P44 monoclonal antibody. P44s are the most
      abundant outer membrane proteins and neutralizing targets of A. phagocytophilum.
      The P44 protein demonstrates characteristics consistent with porins of gram
      negative bacteria, including detergent solubility, heat modifiability, a
      predicted structure of amphipathic and antiparallel beta-strands, an abundance of
      polar residues, and a C-terminal phenylalanine. We purified native P44s under two
      different nondenaturing conditions. When reconstituted into proteoliposomes, both
      purified P44s exhibited porin activity. P44s are encoded by approximately 100 p44
      paralogs and go through extensive antigenic variation. The 16-transmembrane
      domain beta-strands consist of conserved P44 N- and C-terminal regions. By
      looping out the hypervariable region, the porin structure is conserved among
      diverse P44 proteins yet enables antigenic variation for immunoevasion. The
      tricarboxylic acid (TCA) cycle of A. phagocytophilum is incomplete and requires
      the exogenous acquisition of L-glutamine or L-glutamate for function. Efficient
      diffusion of L-glutamine across the outer membrane suggests that the porin feeds
      the Anaplasma TCA cycle and that the relatively large pore size provides
      Anaplasma with the necessary metabolic intermediates from the host cytoplasm.

PMID- 17172335
TI  - Disruption of sitA compromises Sinorhizobium meliloti for manganese uptake
      required for protection against oxidative stress.
AB  - During the initial stages of symbiosis with the host plant Medicago sativa,
      Sinorhizobium meliloti must overcome an oxidative burst produced by the plant in
      order for proper symbiotic development to continue. While identifying mutants
      defective in symbiosis and oxidative stress defense, we isolated a mutant with a
      transposon insertion mutation of sitA, which encodes the periplasmic binding
      protein of the putative iron/manganese ABC transporter SitABCD. Disruption of
      sitA causes elevated sensitivity to the reactive oxygen species hydrogen peroxide
      and superoxide. Disruption of sitA leads to elevated catalase activity and a
      severe decrease in superoxide dismutase B (SodB) activity and protein level. The
      decrease in SodB level strongly correlates with the superoxide sensitivity of the
      sitA mutant. We demonstrate that all free-living phenotypes of the sitA mutant
      can be rescued by the addition of exogenous manganese but not iron, a result that
      strongly implies that SitABCD plays an important role in manganese uptake in S.
      meliloti.

PMID- 17172336
TI  - Export of the pseudopilin XcpT of the Pseudomonas aeruginosa type II secretion
      system via the signal recognition particle-Sec pathway.
AB  - Type IV pilins and pseudopilins are found in various prokaryotic envelope protein
      complexes, including type IV pili and type II secretion machineries of gram
      negative bacteria, competence systems of gram-positive bacteria, and flagella and
      sugar-binding structures in members of the archaeal kingdom. The precursors of
      these proteins have highly conserved N termini, consisting of a short, positively
      charged leader peptide, which is cleaved off by a dedicated peptidase during
      maturation, and a hydrophobic stretch of approximately 20 amino acid residues.
      Which pathway is involved in the inner membrane translocation of these proteins
      is unknown. We used XcpT, the major pseudopilin from the type II secretion
      machinery of Pseudomonas aeruginosa, as a model to study this process. Transport
      of an XcpT-PhoA hybrid was shown to occur in the absence of other Xcp components
      in P. aeruginosa and in Escherichia coli. Experiments with conditional sec
      mutants and reporter-protein fusions showed that this transport process involves
      the cotranslational signal recognition particle targeting route and is dependent
      on a functional Sec translocon.

PMID- 17172337
TI  - Evolution of Mycobacterium ulcerans and other mycolactone-producing mycobacteria
      from a common Mycobacterium marinum progenitor.
AB  - It had been assumed that production of the cytotoxic polyketide mycolactone was
      strictly associated with Mycobacterium ulcerans, the causative agent of Buruli
      ulcer. However, a recent study has uncovered a broader distribution of
      mycolactone-producing mycobacteria (MPM) that includes mycobacteria cultured from
      diseased fish and frogs in the United States and from diseased fish in the Red
      and Mediterranean Seas. All of these mycobacteria contain versions of the M.
      ulcerans pMUM plasmid, produce mycolactones, and show a high degree of genetic
      relatedness to both M. ulcerans and Mycobacterium marinum. Here, we show by
      multiple genetic methods, including multilocus sequence analysis and DNA-DNA
      hybridization, that all MPM have evolved from a common M. marinum progenitor to
      form a genetically cohesive group among a more diverse assemblage of M. marinum
      strains. Like M. ulcerans, the fish and frog MPM show multiple copies of the
      insertion sequence IS2404. Comparisons of pMUM and chromosomal gene sequences
      demonstrate that plasmid acquisition and the subsequent ability to produce
      mycolactone were probably the key drivers of speciation. Ongoing evolution among
      MPM has since produced at least two genetically distinct ecotypes that can be
      broadly divided into those typically causing disease in ectotherms (but also
      having a high zoonotic potential) and those causing disease in endotherms, such
      as humans.

PMID- 17172338
TI  - The Sphingomonas plasmid pCAR3 is involved in complete mineralization of
      carbazole.
AB  - We determined the complete 254,797-bp nucleotide sequence of the plasmid pCAR3, a
      carbazole-degradative plasmid from Sphingomonas sp. strain KA1. A region of about
      65 kb involved in replication and conjugative transfer showed similarity to a
      region of plasmid pNL1 isolated from the aromatic-degrading Novosphingobium
      aromaticivorans strain F199. The presence of many insertion sequences,
      transposons, repeat sequences, and their remnants suggest plasticity of this
      plasmid in genetic structure. Although pCAR3 is thought to carry clustered genes
      for conjugative transfer, a filter-mating assay between KA1 and a pCAR3-cured
      strain (KA1W) was unsuccessful, indicating that pCAR3 might be deficient in
      conjugative transfer. Several degradative genes were found on pCAR3, including
      two kinds of carbazole-degradative gene clusters (car-I and car-II), and genes
      for electron transfer components of initial oxygenase for carbazole (fdxI, fdrI,
      and fdrII). Putative genes were identified for the degradation of anthranilate
      (and), catechol (cat), 2-hydroxypenta-2,4-dienoate (carDFE),
      dibenzofuran/fluorene (dbf/fln), protocatechuate (lig), and phthalate (oph). It
      appears that pCAR3 may carry clustered genes (car-I, car-II, fdxI, fdrI, fdrII,
      and, and cat) for the degradation of carbazole into tricarboxylic acid cycle
      intermediates; KA1W completely lost the ability to grow on carbazole, and the
      carbazole-degradative genes listed above were all expressed when KA1 was grown on
      carbazole. Reverse transcription-PCR analysis also revealed that the
      transcription of car-I, car-II, and cat genes was induced by carbazole or its
      metabolic intermediate. Southern hybridization analyses with probes prepared from
      car-I, car-II, repA, parA, traI, and traD genes indicated that several
      Sphingomonas carbazole degraders have DNA regions similar to parts of pCAR3.

PMID- 17172339
TI  - The timing of cotE expression affects Bacillus subtilis spore coat morphology but
      not lysozyme resistance.
AB  - The synthesis of structural components and morphogenetic factors required for the
      assembly of the Bacillus subtilis spore coat is governed by a mother cell
      specific transcriptional cascade. The first two temporal classes of gene
      expression, which involve RNA polymerase sigma sigma(E) factor and the ancillary
      regulators GerR and SpoIIID, are deployed prior to engulfment of the prespore by
      the mother cell. The two last classes rely on sigma(K), whose activation follows
      engulfment completion, and GerE. The cotE gene codes for a morphogenetic protein
      essential for the assembly of the outer coat layer and spore resistance to
      lysozyme. cotE is expressed first from a sigma(E)-dependent promoter and, in a
      second stage, from a promoter that additionally requires SpoIIID and that remains
      active under sigma(K) control. CotE localizes prior to engulfment completion
      close to the surface of the developing spore, but formation of the outer coat is
      a late, sigma(K)-controlled event. We have transplanted cotE to progressively
      later classes of mother cell gene expression. This created an early class of
      mutants in which cotE is expressed prior to engulfment completion and a late
      class in which expression of cotE follows the complete engulfment of the
      prespore. Mutants of the early class assemble a nearly normal outer coat
      structure, whereas mutants of the late class do not. Hence, the early expression
      of CotE is essential for outer coat assembly. Surprisingly, however, all mutants
      were fully resistant to lysozyme. The results suggest that CotE has genetically
      separable functions in spore resistance to lysozyme and spore outer coat
      assembly.

PMID- 17172340
TI  - In vitro analysis of rates and spectra of mutations in a polymorphic region of
      the Rv0746 PE_PGRS gene of Mycobacterium tuberculosis.
AB  - An assay modeled on a known polymorphism in the PE_PGRS9 gene of Mycobacterium
      tuberculosis was designed to assess the mutability of a sequence containing
      interspersed PGRS repeats. Application of the assay in Mycobacterium smegmatis
      revealed sequence plasticity: in addition to recapitulating the mutation on which
      it was based, other mutations likely mediated by replication slippage between
      PGRS repeats were detected. However, the mutation rates argued against marked
      hypermutability of such sequences in mycobacteria.

PMID- 17172341
TI  - Altered levels of Salmonella DNA adenine methylase are associated with defects in
      gene expression, motility, flagellar synthesis, and bile resistance in the
      pathogenic strain 14028 but not in the laboratory strain LT2.
AB  - Comparative genomic analysis has revealed limited strain diversity between
      Salmonella pathogenic and nonpathogenic isolates. Thus, some of the relative
      virulence and host-immune response disparities may be credited to differential
      gene regulation rather than gross differences in genomic content. Here we show
      that altered levels of Salmonella DNA adenine methylase (Dam) resulted in acute
      defects in virulence-associated gene expression, motility, flagellin synthesis,
      and bile resistance in the Salmonella pathogenic strain 14028 but not in
      avirulent laboratory strain LT2. The defects in motility exhibited by 14028 in
      response to altered Dam levels was not dependent on the presence of the
      regulatory protein, RpoS. The transitioning between flagellar types (phase
      variation) was also differentially regulated in 14028 versus LT2 in response to
      dam levels, resulting in distinct differences in flagellin expression states.
      These data suggest that differential gene regulation may contribute to the
      relative virulence disparities observed between Salmonella serovars that are
      closely related at the DNA level.

PMID- 17172342
TI  - First complete genome sequence of two Staphylococcus epidermidis bacteriophages.
AB  - Staphylococcus epidermidis is an important opportunistic pathogen causing
      nosocomial infections and is often associated with infections in patients with
      implanted prosthetic devices. A number of virulence determinants have been
      identified in S. epidermidis, which are typically acquired through horizontal
      gene transfer. Due to the high recombination potential, bacteriophages play an
      important role in these transfer events. Knowledge of phage genome sequences
      provides insights into phage-host biology and evolution. We present the complete
      genome sequence and a molecular characterization of two S. epidermidis phages,
      phiPH15 (PH15) and phiCNPH82 (CNPH82). Both phages belonged to the Siphoviridae
      family and produced stable lysogens. The PH15 and CNPH82 genomes displayed high
      sequence homology; however, our analyses also revealed important functional
      differences. The PH15 genome contained two introns, and in vivo splicing of phage
      mRNAs was demonstrated for both introns. Secondary structures for both introns
      were also predicted and showed high similarity to those of Streptococcus
      thermophilus phage 2972 introns. An additional finding was differential
      superinfection inhibition between the two phages that corresponded with
      differences in nucleotide sequence and overall gene content within the lysogeny
      module. We conducted phylogenetic analyses on all known Siphoviridae, which
      showed PH15 and CNPH82 clustering with Staphylococcus aureus, creating a novel
      clade within the S. aureus group and providing a higher overall resolution of the
      siphophage branch of the phage proteomic tree than previous studies. Until now,
      no S. epidermidis phage genome sequences have been reported in the literature,
      and thus this study represents the first complete genomic and molecular
      description of two S. epidermidis phages.

PMID- 17172343
TI  - Loss of a universal tRNA feature.
AB  - tRNA(His) has thus far always been found with one of the most distinctive of tRNA
      features, an extra 5' nucleotide that is usually a guanylate. tRNA(His) genes in
      a disjoint alphaproteobacterial group comprising the Rhizobiales,
      Rhodobacterales, Caulobacterales, Parvularculales, and Pelagibacter generally
      fail to encode this extra guanylate, unlike those of other alphaproteobacteria
      and bacteria in general. Rather than adding an extra 5' guanylate
      posttranscriptionally as eukaryotes do, evidence is presented here that two of
      these species, Sinorhizobium meliloti and Caulobacter crescentus, simply lack any
      extra nucleotide on tRNA(His). This loss correlates with changes at the 3' end
      sequence of tRNA(His) and at many sites in histidyl-tRNA synthetase that might be
      expected to affect tRNA(His) recognition, in the flipping loop, the insertion
      domain, the anticodon-binding domain, and the motif 2 loop. The altered tRNA
      charging system may have affected other tRNA charging systems in these bacteria;
      for example, a site in tRNA(Glu) sequences was found to covary with tRNA(His)
      among alphaproteobacteria.

PMID- 17172344
TI  - "Cold-sensitive" mutants of the Lac repressor.
AB  - Thirteen of more than 4,000 single-amino-acid-replacement mutants of the Lac
      repressor, generated by suppression of amber nonsense mutants, were characterized
      as having a cold-sensitive phenotype. However, when expressed as missense
      mutations, none of the replacements cause cold sensitivity, implicating the
      suppression mechanism as being responsible for this phenotype.

PMID- 17172345
TI  - Physiologic effects of forced down-regulation of dnaK and groEL expression in
      Streptococcus mutans.
AB  - Strains of Streptococcus mutans lacking DnaK or GroEL appear not to be isolable.
      To better distinguish the roles played by these chaperones/chaperonins in the
      physiology of S. mutans, we created a knockdown strategy to lower the levels of
      DnaK by over 95% in strain SM12 and the level of GroEL about 80% in strain SM13.
      Interestingly, GroEL levels were approximately twofold higher in SM12 than in the
      parent strain, but the levels of DnaK were not altered in the GroEL knockdown
      strain. Both SM12 and SM13 grew slower than the parent strain, had a strong
      tendency to aggregate in broth culture, and showed major changes in their
      proteomes. Compared with the wild-type strain, SM12 and SM13 had impaired biofilm
      forming capacities when grown in the presence of glucose. The SM12 strain was
      impaired in its capacity to grow at 44 degrees C or at pH 5.0 and was more
      susceptible to H(2)O(2), whereas SM13 behaved like the wild-type strain under
      these conditions. Phenotypical reversions were noted for both mutants when cells
      were grown in continuous culture at a low pH, suggesting the occurrence of
      compensatory mutations. These results demonstrate that DnaK and GroEL
      differentially affect the expression of key virulence traits, including biofilm
      formation and acid tolerance, and support that these chaperones have evolved to
      accommodate unique roles in the context of this organism and its niche.

PMID- 17172346
TI  - The crystal structure of Rv0813c from Mycobacterium tuberculosis reveals a new
      family of fatty acid-binding protein-like proteins in bacteria.
AB  - The gene Rv0813c from Mycobacterium tuberculosis, which codes for a hypothetical
      protein of unknown function, is conserved within the order Actinomycetales but
      absent elsewhere. The crystal structure of Rv0813c reveals a new family of
      proteins that resemble the fatty acid-binding proteins (FABPs) found in
      eukaryotes. Rv0813c adopts the 10-stranded beta-barrel fold typical of FABPs but
      lacks the double-helix insert that covers the entry to the binding site in the
      eukaryotic proteins. The barrel encloses a deep cavity, at the bottom of which a
      small cyclic ligand was found to bind to the hydroxyl group of Tyr192. This
      residue is part of a conserved Arg-X-Tyr motif much like the triad that binds the
      carboxylate group of fatty acids in FABPs. Most of the residues forming the
      internal surface of the cavity are conserved in homologous protein sequences
      found in CG-rich prokaryotes, strongly suggesting that Rv0813c is a member of a
      new family of bacterial FABP-like proteins that may have roles in the
      recognition, transport, and/or storage of small molecules in the bacterial
      cytosol.

PMID- 17172347
TI  - The Pseudomonas quorum-sensing regulator RsaL belongs to the tetrahelical
      superclass of H-T-H proteins.
AB  - In the opportunistic human pathogen Pseudomonas aeruginosa, quorum sensing (QS)
      is crucial for virulence. The RsaL protein directly represses the transcription
      of lasI, the synthase gene of the main QS signal molecule. On the basis of
      sequence homology, RsaL cannot be predicted to belong to any class of
      characterized DNA-binding proteins. In this study, an in silico model of the RsaL
      structure was inferred showing that RsaL belongs to the tetrahelical superclass
      of helix-turn-helix proteins. The overall structure of RsaL is very similar to
      the N-terminal domain of the lambda cI repressor and to the POU-specific domain
      of the mammalian transcription factor Oct-1 (Oct-1 POUs). Moreover, residues of
      Oct-1 POUs important for structural stability and/or DNA binding are conserved in
      the same positions in RsaL and in its homologs found in GenBank. These residues
      were independently replaced with Ala, and the activities of the mutated variants
      of RsaL were compared to that of the wild-type counterpart in vivo by
      complementation assays and in vitro by electrophoretic mobility shift assays. The
      results validated the RsaL in silico model and showed that residues Arg 20, Gln
      38, Ser 42, Arg 43, and Glu 45 are important for RsaL function. Our data indicate
      that RsaL could be the founding member of a new protein family within the
      tetrahelical superclass of helix-turn-helix proteins. Finally, the minimum DNA
      sequence required for RsaL binding on the lasI promoter was determined, and our
      data support the hypothesis that RsaL binds DNA as a dimer.

PMID- 17172348
TI  - A gene cluster involved in degradation of substituted salicylates via ortho
      cleavage in Pseudomonas sp. strain MT1 encodes enzymes specifically adapted for
      transformation of 4-methylcatechol and 3-methylmuconate.
AB  - Pseudomonas sp. strain MT1 has recently been reported to degrade 4- and 5
      chlorosalicylate by a pathway assumed to consist of a patchwork of reactions
      comprising enzymes of the 3-oxoadipate pathway. Genes encoding the initial steps
      in the degradation of salicylate and substituted derivatives were now localized
      and sequenced. One of the gene clusters characterized (sal) showed a novel gene
      arrangement, with salA, encoding a salicylate 1-hydroxylase, being clustered with
      salCD genes, encoding muconate cycloisomerase and catechol 1,2-dioxygenase,
      respectively, and was expressed during growth on salicylate and chlorosalicylate.
      A second gene cluster (cat), exhibiting the typical catRBCA arrangement of genes
      of the catechol branch of the 3-oxoadipate pathway in Pseudomonas strains, was
      expressed during growth on salicylate. Despite their high sequence similarities
      with isoenzymes encoded by the cat gene cluster, the catechol 1,2-dioxygenase and
      muconate cycloisomerase encoded by the sal cluster showed unusual kinetic
      properties. Enzymes were adapted for turnover of 4-chlorocatechol and 3
      chloromuconate; however, 4-methylcatechol and 3-methylmuconate were identified as
      the preferred substrates. Investigation of the substrate spectrum identified 4-
      and 5-methylsalicylate as growth substrates, which were effectively converted by
      enzymes of the sal cluster into 4-methylmuconolactone, followed by isomerization
      to 3-methylmuconolactone. The function of the sal gene cluster is therefore to
      channel both chlorosubstituted and methylsubstituted salicylates into a catechol
      ortho cleavage pathway, followed by dismantling of the formed substituted
      muconolactones through specific pathways.

PMID- 17172351
TI  - A phase II randomized study of two taxanes and cisplatin for metastatic breast
      cancer after anthracycline: a final analysis.
AB  - OBJECTIVE: The purpose of the study is to compare two taxanes/cisplatin
      combinations for metastatic breast cancer in terms of time to disease
      progression, response rates and toxicity. METHODS: Between April 2000 and
      December 2002, 101 patients with advanced breast carcinoma, previously treated
      with an anthracycline but not with a taxane, were enrolled. Fifty patients were
      treated with docetaxel 60 mg/m2 and cisplatin 50 mg/m2, and 51 patients were
      treated with paclitaxel 175 mg/m2 and cisplatin 50 mg/m2. Each cycle repeated
      every 3 weeks. RESULTS: The overall response rate was 62.5 and 42.6% in the
      docetaxel and palcitaxel groups respectively (P = 0.06). Median time to disease
      progression was 9.8 and 6.5 months in docetaxel and paclitaxel groups
      respectively (P = 0.15). The median overall survival time was 22.7 months in the
      docetaxel arm and 22.4 months in the paclitaxel arm. Grade 3/4
      arthralgia/myalgia, sensory neuropathy and anemia occurred more frequently in the
      paclitaxel arm, while more mucositis, fatigue and neutropenia occurred in the
      docetaxel arm. CONCLUSION: Taxane/cisplatin combinations were active for advanced
      breast cancer, while there appeared to be evidence in favor of a
      docetaxel/cisplatin combination. The toxicity in favor of docetaxel/cisplatin
      warrants future first-line clinical trials.

PMID- 17172349
TI  - Oxygen reactivity of both respiratory oxidases in Campylobacter jejuni: the cydAB
      genes encode a cyanide-resistant, low-affinity oxidase that is not of the
      cytochrome bd type.
AB  - The microaerophilic bacterium Campylobacter jejuni is a significant food-borne
      pathogen and is predicted to possess two terminal respiratory oxidases with
      unknown properties. Inspection of the genome reveals an operon (cydAB) apparently
      encoding a cytochrome bd-like oxidase homologous to oxidases in Escherichia coli
      and Azotobacter vinelandii. However, C. jejuni cells lacked all spectral signals
      characteristic of the high-spin hemes b and d of these oxidases. Mutation of the
      cydAB operon of C. jejuni did not have a significant effect on growth, but the
      mutation reduced formate respiration and the viability of cells cultured in 5%
      oxygen. Since cyanide resistance of respiration was diminished in the mutant, we
      propose that C. jejuni CydAB be renamed CioAB (cyanide-insensitive oxidase), as
      in Pseudomonas aeruginosa. We measured the oxygen affinity of each oxidase, using
      a highly sensitive assay that exploits globin deoxygenation during respiration
      catalyzed oxygen uptake. The CioAB-type oxidase exhibited a relatively low
      affinity for oxygen (K(m) = 0.8 microM) and a V(max) of >20 nmol/mg/s. Expression
      of cioAB was elevated fivefold in cells grown at higher rates of oxygen
      provision. The alternative, ccoNOQP-encoded cyanide-sensitive oxidase, expected
      to encode a cytochrome cb'-type enzyme, plays a major role in the microaerobic
      respiration of C. jejuni, since it appeared to be essential for viability and
      exhibited a much higher oxygen affinity, with a K(m) value of 40 nM and a V(max)
      of 6 to 9 nmol/mg/s. Low-temperature photodissociation spectrophotometry revealed
      that neither oxidase has ligand-binding activity typical of the heme-copper
      oxidase family. These data are consistent with cytochrome oxidation during
      photolysis at low temperatures.

PMID- 17172352
TI  - Two Arabidopsis threonine aldolases are nonredundant and compete with threonine
      deaminase for a common substrate pool.
AB  - Amino acids are not only fundamental protein constituents but also serve as
      precursors for many essential plant metabolites. Although amino acid biosynthetic
      pathways in plants have been identified, pathway regulation, catabolism, and
      downstream metabolite partitioning remain relatively uninvestigated. Conversion
      of Thr to Gly and acetaldehyde by Thr aldolase (EC 4.1.2.5) was only recently
      shown to play a role in plant amino acid metabolism. Whereas one Arabidopsis
      thaliana Thr aldolase (THA1) is expressed primarily in seeds and seedlings, the
      other (THA2) is expressed in vascular tissue throughout the plant. Metabolite
      profiling of tha1 mutants identified a >50-fold increase in the seed Thr content,
      a 50% decrease in seedling Gly content, and few other significant metabolic
      changes. By contrast, homozygous tha2 mutations cause a lethal albino phenotype.
      Rescue of tha2 mutants and tha1 tha2 double mutants by overproduction of feedback
      insensitive Thr deaminase (OMR1) shows that Gly formation by THA1 and THA2 is not
      essential in Arabidopsis. Seed-specific expression of feedback-insensitive Thr
      deaminase in both tha1 and tha2 Thr aldolase mutants greatly increases seed Ile
      content, suggesting that these two Thr catabolic enzymes compete for a common
      substrate pool.

PMID- 17172353
TI  - An integrated view of gene expression and solute profiles of Arabidopsis tumors:
      a genome-wide approach.
AB  - Transformation of plant cells with T-DNA of virulent agrobacteria is one of the
      most extreme triggers of developmental changes in higher plants. For rapid growth
      and development of resulting tumors, specific changes in the gene expression
      profile and metabolic adaptations are required. Increased transport and metabolic
      fluxes are critical preconditions for growth and tumor development. A functional
      genomics approach, using the Affymetrix whole genome microarray (approximately
      22,800 genes), was applied to measure changes in gene expression. The solute
      pattern of Arabidopsis thaliana tumors and uninfected plant tissues was compared
      with the respective gene expression profile. Increased levels of anions, sugars,
      and amino acids were correlated with changes in the gene expression of specific
      enzymes and solute transporters. The expression profile of genes pivotal for
      energy metabolism, such as those involved in photosynthesis, mitochondrial
      electron transport, and fermentation, suggested that tumors produce C and N
      compounds heterotrophically and gain energy mainly anaerobically. Thus,
      understanding of gene-to-metabolite networks in plant tumors promotes the
      identification of mechanisms that control tumor development.

PMID- 17172354
TI  - Structural basis for dual functionality of isoflavonoid O-methyltransferases in
      the evolution of plant defense responses.
AB  - In leguminous plants such as pea (Pisum sativum), alfalfa (Medicago sativa),
      barrel medic (Medicago truncatula), and chickpea (Cicer arietinum), 4'-O
      methylation of isoflavonoid natural products occurs early in the biosynthesis of
      defense chemicals known as phytoalexins. However, among these four species, only
      pea catalyzes 3-O-methylation that converts the pterocarpanoid isoflavonoid 6a
      hydroxymaackiain to pisatin. In pea, pisatin is important for chemical resistance
      to the pathogenic fungus Nectria hematococca. While barrel medic does not
      biosynthesize 6a-hydroxymaackiain, when cell suspension cultures are fed 6a
      hydroxymaackiain, they accumulate pisatin. In vitro, hydroxyisoflavanone 4'-O
      methyltransferase (HI4'OMT) from barrel medic exhibits nearly identical steady
      state kinetic parameters for the 4'-O-methylation of the isoflavonoid
      intermediate 2,7,4'-trihydroxyisoflavanone and for the 3-O-methylation of the 6a
      hydroxymaackiain isoflavonoid-derived pterocarpanoid intermediate found in pea.
      Protein x-ray crystal structures of HI4'OMT substrate complexes revealed
      identically bound conformations for the 2S,3R-stereoisomer of 2,7,4'
      trihydroxyisoflavanone and the 6aR,11aR-stereoisomer of 6a-hydroxymaackiain.
      These results suggest how similar conformations intrinsic to seemingly distinct
      chemical substrates allowed leguminous plants to use homologous enzymes for two
      different biosynthetic reactions. The three-dimensional similarity of natural
      small molecules represents one explanation for how plants may rapidly recruit
      enzymes for new biosynthetic reactions in response to changing physiological and
      ecological pressures.

PMID- 17172355
TI  - Pollen tube tip growth depends on plasma membrane polarization mediated by
      tobacco PLC3 activity and endocytic membrane recycling.
AB  - Phosphatidyl inositol 4,5-bisphosphate (PI 4,5-P2) accumulates in a Rac/Rop
      dependent manner in the pollen tube tip plasma membrane, where it may control
      actin organization and membrane traffic. PI 4,5-P2 is hydrolyzed by phospholipase
      C (PLC) activity to the signaling molecules inositol 1,4,5-trisphosphate and
      diacyl glycerol (DAG). To investigate PLC activity during tip growth, we cloned
      Nt PLC3, specifically expressed in tobacco (Nicotiana tabacum) pollen tubes.
      Recombinant Nt PLC3 displayed Ca2+-dependent PI 4,5-P2-hydrolyzing activity
      sensitive to U-73122 and to mutations in the active site. Nt PLC3 overexpression,
      but not that of inactive mutants, inhibited pollen tube growth. Yellow
      fluorescent protein (YFP) fused to Nt PLC3, or to its EF and C2 domains,
      accumulated laterally at the pollen tube tip plasma membrane in a pattern
      complementary to the distribution of PI 4,5-P2. The DAG marker Cys1:YFP displayed
      a similar intracellular localization as PI 4,5-P2. Blocking endocytic membrane
      recycling affected the intracellular distribution of DAG but not of PI 4,5-P2. U
      73122 at low micromolar concentrations inhibited and partially depolarized pollen
      tube growth, caused PI 4,5-P2 spreading at the apex, and abolished DAG membrane
      accumulation. We show that Nt PLC3 is targeted by its EF and C2 domains to the
      plasma membrane laterally at the pollen tube tip and that it maintains, together
      with endocytic membrane recycling, an apical domain enriched in PI 4,5-P2 and DAG
      required for polar cell growth.

PMID- 17172356
TI  - The female gametophyte and the endosperm control cell proliferation and
      differentiation of the seed coat in Arabidopsis.
AB  - Double fertilization of the female gametophyte produces the endosperm and the
      embryo enclosed in the maternal seed coat. Proper seed communication necessitates
      exchanges of signals between the zygotic and maternal components of the seed.
      However, the nature of these interactions remains largely unknown. We show that
      double fertilization of the Arabidopsis thaliana female gametophyte rapidly
      triggers sustained cell proliferation in the seed coat. Cell proliferation and
      differentiation of the seed coat occur in autonomous seeds produced in the
      absence of fertilization of the multicopy suppressor of ira1 (msi1) mutant. As
      msi1 autonomous seeds mostly contain autonomous endosperm, our results indicate
      that the developing endosperm is sufficient to enhance cell proliferation and
      differentiation in the seed coat. We analyze the effect of autonomous
      proliferation in the retinoblastoma-related1 (rbr1) female gametophyte on seed
      coat development. In contrast with msi1, supernumerary nuclei in rbr1 female
      gametophytes originate mainly from the endosperm precursor lineage but do not
      express an endosperm fate marker. In addition, defects of the rbr1 female
      gametophyte also reduce cell proliferation in the ovule integuments before
      fertilization and prevent further differentiation of the seed coat. Our data
      suggest that coordinated development of the seed components relies on
      interactions before fertilization between the female gametophyte and the
      surrounding maternal ovule integuments and after fertilization between the
      endosperm and the seed coat.

PMID- 17172357
TI  - The coactivator function of Arabidopsis NPR1 requires the core of its BTB/POZ
      domain and the oxidation of C-terminal cysteines.
AB  - NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) regulates systemic acquired
      resistance (SAR) in Arabidopsis thaliana, and current models propose that after
      treatment with salicylic acid (SA), Cys-82 and Cys-216 of NPR1 are reduced,
      leading to nuclear import. The interaction of nucleus-localized NPR1 with TGA
      transcription factors results in the activation of defense genes, including the
      SAR marker PATHOGENESIS-RELATED-1 (PR-1), and the deployment of SAR. Little is
      known about how TGA factors or NPR1 regulate transcription or whether a TGA-NPR1
      complex forms on DNA. We show that TGA2 and NPR1 are recruited to PR-1
      independently of each other and of SA treatment. Consistent with the result that
      a triple knockout in TGA2/5/6 derepresses PR-1, in vivo plant transcription
      assays revealed that TGA2 is not an autonomous transcription activator but is a
      transcriptional repressor in both untreated and SA-treated cells. However, after
      stimulation with SA, TGA2 is incorporated into a transactivating complex with
      NPR1, forming an enhanceosome that requires the core of the NPR1 BTB/POZ domain
      (residues 80 to 91) and the oxidation of NPR1 Cys-521 and Cys-529. These Cys
      residues are found in a new type of transactivation domain that we term Cys
      oxidized. These data further our understanding of the mechanism by which TGA2 and
      NPR1 activate Arabidopsis PR-1.

PMID- 17172360
TI  - MDR-TB and HIV: the perfect storm?

PMID- 17172359
TI  - The cauliflower Or gene encodes a DnaJ cysteine-rich domain-containing protein
      that mediates high levels of beta-carotene accumulation.
AB  - Despite recent progress in our understanding of carotenogenesis in plants, the
      mechanisms that govern overall carotenoid accumulation remain largely unknown.
      The Orange (Or) gene mutation in cauliflower (Brassica oleracea var botrytis)
      confers the accumulation of high levels of beta-carotene in various tissues
      normally devoid of carotenoids. Using positional cloning, we isolated the gene
      representing Or and verified it by functional complementation in wild-type
      cauliflower. Or encodes a plastid-associated protein containing a DnaJ Cys-rich
      domain. The Or gene mutation is due to the insertion of a long terminal repeat
      retrotransposon in the Or allele. Or appears to be plant specific and is highly
      conserved among divergent plant species. Analyses of the gene, the gene product,
      and the cytological effects of the Or transgene suggest that the functional role
      of Or is associated with a cellular process that triggers the differentiation of
      proplastids or other noncolored plastids into chromoplasts for carotenoid
      accumulation. Moreover, we demonstrate that Or can be used as a novel genetic
      tool to induce carotenoid accumulation in a major staple food crop. We show here
      that controlling the formation of chromoplasts is an important mechanism by which
      carotenoid accumulation is regulated in plants.

PMID- 17172358
TI  - Rice XA21 binding protein 3 is a ubiquitin ligase required for full Xa21-mediated
      disease resistance.
AB  - XA21 is a receptor-like kinase protein in rice (Oryza sativa) that confers gene
      for-gene resistance to specific races of the causal agent of bacterial blight
      disease, Xanthomonas oryzae pv oryzae. We identified XA21 binding protein 3
      (XB3), an E3 ubiquitin ligase, as a substrate for the XA21 Ser and Thr kinase.
      The interaction between XB3 and the kinase domain of XA21 has been shown in yeast
      and in vitro, and the physical association between XB3 and XA21 in vivo has also
      been confirmed by coimmunoprecipitation assays. XB3 contains an ankyrin repeat
      domain and a RING finger motif that is sufficient for its interaction with the
      kinase domain of XA21 and for its E3 ubiquitin ligase activity, respectively.
      Transgenic plants with reduced expression of the Xb3 gene are compromised in
      resistance to the avirulent race of X. oryzae pv oryzae. Furthermore, reduced
      levels of Xb3 lead to decreased levels of the XA21 protein. These results
      indicate that Xb3 is necessary for full accumulation of the XA21 protein and for
      Xa21-mediated resistance.

PMID- 17172361
TI  - Tuberculosis mortality, drug resistance, and infectiousness in patients with and
      without HIV infection in Peru.
AB  - The effects of HIV co-infection and multi-drug resistant tuberculosis (MDRTB) on
      tuberculosis prognosis are poorly defined. Therefore, we studied infectiousness
      and mortality of 287 tuberculosis patients treated with standard, directly
      observed, short-course therapy in the Peruvian community. During 6-17 months of
      treatment, 49 (18%) of patients died, of whom 48 (98%) had AIDS and 28 (57%) had
      MDRTB; 17/31 (55%) of MDRTB-patients with AIDS died within 2 months of diagnosis,
      before traditional susceptibility testing would have identified their MDRTB. Most
      non-MDRTB became smear- and culture-negative within 6 weeks of therapy, whereas
      most MDRTB remained sputum-culture-positive until death or treatment completion.
      HIV-negative patients with non-MDRTB had good outcomes. However, MDRTB was
      associated with prolonged infectiousness and HIV co-infection with early
      mortality, indicating a need for greater access to anti-retroviral therapy.
      Furthermore, early and rapid tuberculosis drug-susceptibility testing and
      infection control are required so that MDRTB can be appropriately treated early
      enough to reduce mortality and transmission.

PMID- 17172362
TI  - Spatial and temporal variations in local transmission of Schistosoma haematobium
      in Msambweni, Kenya.
AB  - As part of an extensive study of the eco-epidemiology of urinary schistosomiasis
      along the southern coast of Kenya, spatial and temporal transmission patterns
      were associated with various ponds infested with Bulinus snails. The household
      level spatial pattern of infection for children of various age groups in 2000 was
      contrasted with historical data from 1984. Significant local clustering of high
      and low infection levels among school age children was detected, and the spatial
      extent of clusters and their direction from specific water sources were measured.
      High infection levels were clustered around ponds known to contain Bulinus
      nasutus snails that shed Schistosoma haematobium cercariae, and low infection
      levels were concentrated near a river where intermediate host snails were rarely
      found. The spatial patterns of infection varied between 2000 and 1984 and between
      age groups. High levels of infection were clustered around different transmission
      foci in the two study periods, and, for younger children in 2000, were clustered
      nearer to the transmission foci than for the older children. Simultaneous
      consideration of the effects of different foci on transmission will allow for
      targeted application of control measures aimed at interrupting S. haematobium
      transmission at a local level.

PMID- 17172363
TI  - Assessment of ultrasound morbidity indicators of schistosomiasis in the context
      of large-scale programs illustrated with experiences from Malian children.
AB  - We assessed morbidity indicators for both Schistosoma haematobium and Schistosoma
      mansoni infections and evaluated the appropriateness of the World Health
      Organization (WHO) guidelines for ultrasound in schistosomiasis in the context of
      large-scale control interventions. Abdominal and urinary tract ultrasonography
      was performed on 2,247 and 2,822 school children, respectively, from 29 randomly
      selected schools in Mali before the implementation of mass anthelminthic drug
      administration. Using two-level logistic regression models, we examined
      associations of potential factors with the risk of having a positive ultrasound
      global score (morbidity indicative of S. haematobium infection), abnormal image
      pattern scores, dilatation of the portal vein, and/or enlarged liver (morbidity
      indicative of S. mansoni infection). The WHO protocol was found useful for
      detection of S. haematobium pathology but overestimated the risk of portal vein
      dilatation and left liver lobe enlargement associated with S. mansoni infection.
      We conclude that ultrasonography should be included in large-scale control
      interventions, where logistics allow, but cautiously.

PMID- 17172364
TI  - Higher percentages of circulating mast cell precursors correlate with
      susceptibility to reinfection with Schistosoma mansoni.
AB  - A high level of serum IgE is generally associated with human resistance to
      schistosomes, though the protective mechanisms of IgE remain undefined. We
      recently reported that whereas some individuals who are occupationally
      hyperexposed to Schistosoma mansoni display resistance to reinfection, others
      remain highly susceptible, in some cases due to HIV-1 co-infection. As IgE
      functions, in part, through FcepsilonRI on mast cells, we characterized
      circulating CD117(+) FcepsilonRI(+) mast cell precursors in this population.
      Surprisingly, a higher percentage of CD117(+) cells correlated with a susceptible
      phenotype in HIV-1 seronegative participants with schistosomiasis. There was no
      association between percentages of peripheral CD117(+) cells and susceptibility
      to reinfection in persons with HIV-1. Serum levels of polyclonal IgE were
      inversely correlated with percentages of CD117(+) cells regardless of HIV-1
      status. Thus, immature mast cells may affect IgE availability, or IgE may affect
      immature mast cells, altering the balance of host susceptibility and resistance
      to schistosomes.

PMID- 17172365
TI  - The reliability of anterior segment lesions as indicators of onchocercal eye
      disease in Guatemala.
AB  - World Health Organization certification criteria for onchocerciasis elimination
      use anterior segment eye lesion prevalence as an indicator of mass ivermectin
      treatment program success. Lesions either contain visible microfilaria
      (noninflammatory punctate keratitis [PK] or microfilariae in anterior chamber
      [MFAC]), or microfilaria obscured by inflammation (inflammatory PK). To assess
      the utility of these disease indicators, two experienced ophthalmologists
      independently examined persons from endemic (N = 325) and nonendemic (N = 348)
      Guatemalan communities. Thirty-six (11.1%) and nine (2.6%) persons from endemic
      and nonendemic areas respectively had lesions found by either ophthalmologist
      (prevalence ratio = 4.3, 95% CI 2.1-8.8, P < 0.001). All lesions in nonendemic
      areas were inflammatory PK in whom no persons were seropositive for
      onchocerciasis. Overall, observer agreement was moderate (Kappa = 0.49), and most
      (61%) discordance occurred with inflammatory PK lesions. Our findings suggest
      that inflammatory punctate keratitis is neither a specific nor a reliable
      indicator of onchocercal eye disease. Future prevalence surveys should rely upon
      noninflammatory lesions as disease indicators.

PMID- 17172366
TI  - Community perception of school-based deworming program in Sanliurfa, Turkey.
AB  - This article presents an evaluation of the community perception of the recently
      implemented School Based Health Program, which delivered anthelmintics to 96,000
      schoolchildren in Sanliurfa, Turkey. One hundred forty-four parents and 140
      teachers were interviewed through questionnaires, focus group discussions, and in
      depth interviews. The evaluation indicated that most of the parents and teachers
      reported that the program was beneficial as it led to improvement in children's
      health and well being. The evaluation also indicated that 99% of the parents and
      98.4% of the teachers approved of the teacher's role in this program. Nearly all
      of the teachers and parents showed willingness to continue the program in the
      future and 75% of the parents indicated willingness to pay for the drugs. The
      evaluation also highlighted that there were critical issues for the successful
      implementation of the program such as the issue of educating illiterate mothers,
      higher involvement of families in the mass treatment process, ability to reach a
      larger number of school absentees, and overcoming the prejudice against
      externally funded measures, which are perceived by some of the members of the
      community as an experiment run by foreigners on the local population and the
      concern of some parents that anthelmintic drug (mebendazole) might cause sexual
      sterility.

PMID- 17172367
TI  - Leishmania amazonensis infections in Oryzomys acritus and Oryzomys nitidus from
      Bolivia.
AB  - Three of thirteen Oryzomys acritus, Emmons and Patton 2005 (Rodentia: Muridae:
      Sigmodontinae) and 3 of 17 Oryzomys nitidus, Thomas 1884, collected from Noel
      Kempff National Park, Bolivia, from 2002 to 2005, tested positive for Leishmania
      (Leishmania) amazonensis or L. (L.) mexicana and negative for Leishmania
      (Viannia) spp. using the polymerase chain reaction (PCR). Based on previous
      records of L. (L.) amazonensis in humans, rodents, and sand flies from Bolivia,
      and the geographic distributions of L. (L.) amazonensis and L. (L.) mexicana, it
      was concluded that the Oryzomys were infected with L. (L.) amazonensis. These
      results identify two additional species of Oryzomys as hosts of L. (L.)
      amazonensis, and identify an ecological region of Bolivia where L. (L.)
      amazonensis is enzootic.

PMID- 17172368
TI  - Relapse of new world diffuse cutaneous leishmaniasis caused by Leishmania
      (Leishmania) mexicana after miltefosine treatment.
AB  - A 35-year-old man with a 19-year history of slowly evolving diffuse cutaneous
      leishmaniasis was treated with oral miltefosine, 50 mg three times a day. The
      patient responded after four months of miltefosine treatment with clearance of
      all nodular lesions and plaques from the entire body surface and had negative
      slit-skin smears and cultures for Leishmania. However, two months after stopping
      miltefosine, skin lesions reappeared and parasites were observed in samples. The
      relapsed lesions did not respond to an additional two-month course of
      miltefosine. No laboratory or clinical adverse events to miltefosine were
      observed. Parasites from skin lesions were cultured and identified as Leishmania
      (Leishmania) mexicana by isoenzyme electrophoresis.

PMID- 17172369
TI  - Congenital transmission of Trypanosoma cruzi in Europe (Spain): a case report.
AB  - Here we report a documented case of congenital transmission of Trypanosoma cruzi
      from a Bolivian mother with chronic Chagas disease living in Spain. The serology
      and blood nested polymerase chain reaction (PCR) were positive for the mother,
      and amastigote forms were observed in histopathological study of the placenta and
      umbilical cord. Direct examination, culture, and nested PCR were positive in the
      blood of the neonate. At the age of 8 days, the neonate began treatment with 5
      7.5 mg/kg/day of benznidazol, which was continued for 60 days. Direct
      examination, blood culture, and nested PCR were negative to T. cruzi 20 days
      after the start of treatment and remained negative 4 and 7 months thereafter.
      Serological tests were negative at 4 months. To detect congenital infection and
      initiate early treatment of infected newborns, protocols are required to detect
      Chagas disease in pregnant women who migrate from endemic to non-endemic areas.

PMID- 17172370
TI  - Amniotic fluid is not useful for diagnosis of congenital Trypanosoma cruzi
      infection.
AB  - Although Trypanosoma cruzi can be transmitted transplacentally and induce
      congenital infection, no data are available about the presence of this parasite
      in human amniotic fluid. We examined 8, 19, and 4 amniotic fluid samples
      (collected at delivery or by aspiration of gastric content of neonates) from
      control uninfected mothers (M-B-), infected mothers delivering uninfected
      newborns (M+B-), and mothers of confirmed congenital cases (M+B+), respectively.
      Polymerase chain reaction (PCR), using nuclear and kinetoplastic DNA primers
      (Tcz1-Tcz2 and 121-122), were negative for all control M-B- samples, but positive
      for 5 of 19 M+B- and 2 of 4 M+B+ samples. To determine the number of parasites in
      the positive samples, real-time PCR using S35/S36 kinetoplastic DNA was
      performed. Only one M+B+ sample presented a high parasitic DNA amount, whereas
      the other six PCR-positive samples displayed traces of T. cruzi DNA. In
      conclusion, the release of parasites in amniotic fluid is probably a rare event
      that cannot be helpful for the routine diagnosis of congenital Chagas disease.

PMID- 17172371
TI  - Retrospective serosurvey of leptospirosis among patients with acute febrile
      illness and hepatitis in Egypt.
AB  - The epidemiologic status of leptospirosis in Egypt has not been well defined
      because of difficulties in disease diagnosis. A retrospective study was conducted
      to detect leptospiral antibodies among undiagnosed acute febrile illness (AFI)
      and hepatitis cases. Approximately 16% of both AFI (141/886) and acute hepatitis
      (63/392) cases showed seroreactivity to Leptospira IgM by ELISA and microscopic
      agglutination test (MAT). Canicola, Djasiman, Grippotyphosa, Pyrogenes,
      Icterohemorrhagiae, and Pomona were the most commonly reactive serovars among
      patients with AFI. Djasiman, Grippotyphosa and Icterohemorrhagiae were the most
      reactive among patients with acute hepatitis. This study represents the first
      systematic report of Leptospira associated with patients with AFI and hepatitis
      in Egypt. Physicians need to have increased awareness about the importance of
      leptospirosis in the differential diagnosis of AFI and acute hepatitis in Egypt.
      In addition, laboratory capacity should be developed at fever hospitals to
      diagnose leptospirosis.

PMID- 17172372
TI  - Reinfection and relapse in early Lyme disease.
AB  - To determine whether recurrent episodes of appropriately treated Lyme disease are
      caused by reinfection or relapse, we monitored pertinent clinical manifestations
      and serology of residents of an endemic site each year for 14 years. Of 253
      episodes of early Lyme disease recorded among 213 residents, we observed 40
      recurrent episodes. Virtually all included an erythema migrans (EM) rash that
      appeared at body sites that differed from those of the initial rash, no subjects
      produced detectable levels of specific antibody between sequential episodes, all
      episodes occurred a year or more after the initial EM episode, and all occurred
      during late spring and early summer. People experiencing recurrent episodes
      tended to have frequent contact with vector ticks. Prompt administration of
      standard antibiotic therapy for early Lyme disease reliably eliminates persistent
      infection and prevents relapse.

PMID- 17172373
TI  - Cryptosporidiosis and other intestinal protozoan infections in children less than
      one year of age in Mexico City.
AB  - Parasitic diseases are very important in Mexico because of their economic impact
      and adverse effects on normal growth in children. Cryptosporidiosis has been
      associated with acute diarrhea in immune competent and incompetent human hosts,
      fecal contamination of drinking water sources, and handling of animals. Due to
      the lack of reports on cryptosporidiosis in Mexico, we conducted a parasitologic
      study in children with diarrhea and other clinical symptoms. The main objectives
      were 1) to determine the prevalence of cryptosporidiosis in children less than
      one year of age in Mexico City, and 2) to correlate Cryptosporidium infection
      with gastrointestinal symptoms. Two hundred fecal samples from children seen at
      the Gabriel Mancera Familiar Medicine Unit of the Instituto Mexicano del Seguro
      Social were studied. Children were divided into two groups. Group A was composed
      of sick children with 6-8 watery diarrheic episodes every 24 hours attended at
      the emergency service. Group B was composed of healthy babies getting routine
      check ups. Only children in group A were found to be infected with intestinal
      protozoa (50% with Giardia lamblia, 41% with Cryptosporidium spp., and 4% with
      Entamoeba histolytica). The results suggested a high incidence of Cyrptosporidium
      infections in children in Mexico City, which make these observations useful for
      future studies.

PMID- 17172374
TI  - Rapid diagnosis of scrub typhus in rural Thailand using polymerase chain
      reaction.
AB  - The aim of this study was to evaluate the use of polymerase chain reaction (PCR)
      amplification of the O. tsutsugamushi 16S rRNA gene for the diagnosis of scrub
      typhus in rural Thailand. A prospective study of acute febrile illness in Udon
      Thani, northeast Thailand, identified 183 patients as having scrub typhus on the
      basis of immunofluorescent antibody testing (IFA) of paired sera. A further 366
      febrile patients admitted concurrently with a range of other diagnoses acted as
      negative controls. Diagnostic sensitivity and specificity of 16S rRNA PCR was
      44.8% and 99.7%, respectively, compared with IFA. PCR positivity was related to
      duration of symptoms and presence of eschar (P < 0.001, both cases). PCR using
      primers to amplify a fragment of the 56-kd gene had a sensitivity and specificity
      of 29.0% and 99.2%, respectively. PCR has a high specificity but low sensitivity
      for the rapid diagnosis of scrub typhus in this endemic setting.

PMID- 17172375
TI  - Evaluation of a boosted-p24 antigen assay for the early diagnosis of pediatric
      HIV-1 infection in Cambodia.
AB  - Methods for early diagnosis of pediatric HIV-1 infection (DNA-polymerase chain
      reaction [PCR], RNA quantification, viral cultures) are expensive. Most Cambodian
      infants wait 18 months for HIV serologic tests. We observed that boosted-p24
      antigen profile assay, with performances similar to viral cultures and costs
      similar to DNA-PCR, is easier to perform and could readily be set up in resource
      poor settings.

PMID- 17172376
TI  - Successful treatment of black-grain mycetoma with voriconazole.
AB  - Fungal mycetoma (or eumycetoma) are endemic diseases in tropical areas that have
      economic effects because of their chronic and disabling evolution. Classic
      treatments include surgery and antifungal drugs, but these have multiple side
      effects. We report a case of black-grain fungal mycetoma successfully treated
      with voriconazole without side effects. The duration of the treatment remains
      unclear, but must be prolonged because of the frequency of relapses.

PMID- 17172377
TI  - Oral rehydration solution to prevent nephrotoxicity of amphotericin B.
AB  - Treatment with amphotericin B deoxycholate (AB) is associated with dose-related
      nephrotoxicity. We conducted an open and randomized trial to evaluate the
      efficacy of an oral rehydration solution (ORS) to prevent nephrotoxicity of AB,
      compared with an intravenous saline solution (SS). Adult patients with mucosal
      leishmaniasis in whom AB was indicated received either three liters or ORS or one
      liter of SS. Renal function tests were performed at baseline and during
      treatment. Forty-eight patients were included (ORS = 25, SS = 23). No difference
      was observed in serum creatinine, creatinine clearance, serum urea, and serum
      sodium values during treatment, but serum potassium values were lower in the SS
      group than in the ORS group (P < 0.03). Treatment was more temporarily
      discontinued in the SS group than in the ORS group (7 patients versus 1 patient,
      P = 0.02). We conclude that ORS is comparable to SS in preventing glomerular
      damage of AB, but more effective in preventing hypokalemia.

PMID- 17172378
TI  - Dengue hemorrhagic Fever caused by sequential dengue 1-3 virus infections over a
      long time interval: Havana epidemic, 2001-2002.
AB  - A dengue epidemic caused by dengue virus 3 (DENV-3) occurred in Cuba in 2001
      2002. It included cases of dengue hemorrhagic fever/dengue shock syndrome
      (DHF/DSS). We report neutralizing antibody studies on sera from 54 of 78 DHF/DSS
      patients that provide evidence of infections occurring in the sequence DENV-1
      followed by DENV-3. No sera showed infection in the sequence DENV-2 followed by
      DENV-3. Some sera showed a pattern of infection in the sequence DENV-1 followed
      by DENV-2 and then DENV-3. However definitive categorization of a tertiary
      infection was not possible because of broadly reactive antibodies, which could
      have been raised by infections in the sequence DENV-1 then DENV-3.

PMID- 17172379
TI  - The pathogenicity of mosquito densovirus (C6/36DNV) and its interaction with
      dengue virus type II in Aedes albopictus.
AB  - When Aedes albopictus larvae were infected with C6/36 densovirus (C6/36DNV), the
      mortality reached 97.46% within 21 days for those larvae infected at the first
      day after hatching, and 14.17% for control. A real-time quantitative polymerase
      chain reaction (qPCR) was used to trace the dynamic change of the quantity of
      C6/36DNV genomes in the larvae and the adults, and to study the interaction of
      C6/36DNV with dengue virus type II(DEN-II) in mosquitoes. It showed that C6/36DNV
      could persist in the adults that could transmit C6/36DNV vertically to the next
      generation. The quantity of C6/36DNV after DEN-II infection increased by
      10(2)~10(3) times in the C6/36DNV-positive mosquitoes, and the quantity of DEN-II
      in the C6/36DNV-positive mosquitoes was about 100 times lower than that in the
      C6/36DNV-negative mosquitoes, which suggested that DEN-II could remarkably
      stimulate the reproduction of C6/36DNV, while C6/36DNV persisted in mosquitoes
      could inhibit the reproduction of DEN-II. The study throws light on C6/36DNV as a
      possible biologic control agent against dengue virus and Ae. albopictus.

PMID- 17172380
TI  - Phylogenetic and geographical relationships of hantavirus strains in eastern and
      western Paraguay.
AB  - Recently, we reported the discovery of several potential rodent reservoirs of
      hantaviruses in western (Holochilus chacarius) and eastern Paraguay (Akodon
      montensis, Oligoryzomys chacoensis, and O. nigripes). Comparisons of the
      hantavirus S- and M-segments amplified from these four rodents revealed
      significant differences from each another and from other South American
      hantaviruses. The ALP strain from the semiarid Chaco ecoregion clustered with
      Leguna Negra and Rio Mamore (LN/RM), whereas the BMJ-NEB strain from the more
      humid lower Chaco ecoregion formed a clade with Oran and Bermejo. The other two
      strains, AAI and IP37/38, were distinct from known hantaviruses. With respect to
      the S-segment sequence, AAI from eastern Paraguay formed a clade with ALP/LN/RM,
      but its M-segment clustered with Pergamino and Maciel, suggesting a possible
      reassortment. AAI was found in areas experiencing rapid land cover fragmentation
      and change within the Interior Atlantic Forest. IP37/38 did not show any strong
      association with any of the known hantavirus strains.

PMID- 17172381
TI  - Use of IgG avidity to indirectly monitor epizootic transmission of sin nombre
      virus in deer mice (Peromyscus maniculatus).
AB  - An IgG avidity assay was developed to differentiate deer mice that had recently
      acquired Sin Nombre virus (SNV) from those that were infected in the distant
      past. Using this procedure, low avidity antibodies were predominantly detected in
      experimentally infected deer mice (89.5%) within the first 30 days post
      inoculation. The assay was then applied to sera from naturally infected deer mice
      collected during a field investigation associated with a cluster of hantavirus
      pulmonary syndrome cases. A higher proportion of seropositive mice collected
      during the outbreak had serum with low avidity antibodies (16.7%) when compared
      with mice trapped four months later (5.7%). Sin Nombre virus RNA was detectable
      in blood in a similar fraction of low- (45%) and high- (38.7%) avidity groups.
      Non-adult mice were more likely to contain low-avidity antibodies (44.4%) than
      were adults (9.6%). Our results indicate that the IgG avidity assay shows promise
      as a tool to better characterize epizootic intensity and to identify factors
      involved in SNV transmission.

PMID- 17172382
TI  - Molecular identification of blood-meal sources in Culiseta melanura and Culiseta
      morsitans from an endemic focus of eastern equine encephalitis virus in New York.
AB  - Eastern equine encephalitis (EEE) virus perpetuates in an enzootic cycle
      involving ornithophilic mosquito vectors, principally Culiseta melanura
      (Coquillett) and avian amplification hosts. To better understand the role of Cs.
      melanura and Culiseta morsitans (Theobald) in the epizootiology of EEE virus, we
      collected blood-fed mosquitoes between 31 May and 15 October 2004 at two sites
      associated with an EEE virus focus in central New York and identified the source
      of vertebrate blood by nucleotide sequencing of polymerase chain reaction (PCR)
      products of the cytochrome b gene. Analysis of 484 Cs. melanura and 122 Cs.
      morsitans revealed that 94.2% and 86.9%, respectively, acquired blood solely from
      avian hosts. Blood meals derived exclusively from mammals were detected in 0.8%
      of Cs. melanura and 1.6% of Cs. morsitans. Individual mosquitoes containing mixed
      blood meals from both avian and mammalian hosts were also detected in 5.0% of Cs.
      melanura and 11.5% of Cs. morsitans. Wood thrush constituted the most common
      vertebrate host for Cs. melanura (23.6%) and Cs. morsitans (30.9%), followed by
      American robin, song sparrow, ovenbird, red-eyed vireo, and common yellowthroat.
      Mammalian-derived blood meals were identified as white-tailed deer, horse,
      domestic cat, and eastern pipistrelle bat. There were three isolations of EEE
      virus from Cs. melanura and one from Cs. morsitans. These results suggest that
      wood thrush and a few other passerine birds may play key roles in supporting EEE
      virus transmission in the northeast and possibly throughout the geographic range
      of EEE in North America. The frequency of mammalian feedings also suggests that
      Cs. melanura and Cs. morsitans may play a role in the transmission of EEE virus
      to equines, in addition to maintaining enzootic transmission among avian hosts.
      We report the first isolation of arboviruses from mosquito vectors concomitant
      with the identifications of their blood meal sources.

PMID- 17172384
TI  - Venereal transmission of Chandipura virus by Phlebotomus papatasi (Scopoli).
AB  - Experiments were conducted in the laboratory on Phlebotomus papatasi to determine
      the possible role of males in maintaining or sustaining the Chandipura virus
      (CHPV) activity in nature. This study indicated that infected males are capable
      of passing on the virus to female sand flies while mating. The infection rate was
      found to be 12.5% in uninfected females when mated with infected males. The
      occurrence of venereal transmission of this virus may have epidemiologic
      importance in the natural cycle of CHPV.

PMID- 17172383
TI  - Role of viruses in Kenyan children presenting with acute encephalopathy in a
      malaria-endemic area.
AB  - In malaria-endemic areas, it is difficult to differentiate between cerebral
      malaria (CM), bacterial meningitis, and viral encephalitis. We examined the
      cerebrospinal fluid of 49 children who fulfilled the World Health Organization's
      (WHO) definition of CM and in 47 encephalopathic children, without malaria,
      looking for viruses with polymerase chain reaction. In the children with CM, four
      (9%) had evidence of Herpes simplex virus 1 in the cerebrospinal fluid, whereas
      in the encephalopathy group without malaria, six (12%) were positive. A
      significant proportion of children who fulfil the WHO clinical definition of CM
      may have viral encephalitis.

PMID- 17172385
TI  - Field evaluation of spatial repellency of metofluthrin-impregnated latticework
      plastic strips against Aedes aegypti (L.) and analysis of environmental factors
      affecting its efficacy in My Tho City, Tien Giang, Vietnam.
AB  - Spatial repellency of metofluthrin-impregnated polyethylene latticework plastic
      strips against Aedes aegypti mosquitoes was evaluated. Analysis of environmental
      factors affecting the efficacy of these strips, such as room temperature,
      humidity, and house structure, was performed in a residential area in My Tho
      City, Tien Giang Province, Vietnam. Treatment with the strips at the rate of 1
      strip per 2.6-5.52 m(2) (approximately 600 mg per 2.6-5.52 m(2)) reduced the
      collection of Ae. aegypti resting inside the houses for at least eight weeks.
      Multiple regression analysis indicated that both increase in the average room
      temperature and decrease in the area of openings in the rooms that were treated
      with the strips positively affected the spatial repellency of metofluthrin.

PMID- 17172386
TI  - Manipulation of the yellow fever virus non-structural genes 2A and 4B and the
      3'non-coding region to evaluate genetic determinants of viral dissemination from
      the Aedes aegypti midgut.
AB  - Although much is known about the ecology, epidemiology, and molecular biology of
      mosquito-borne viruses, the viral factors that allow transmission by mosquitoes
      to humans or animals remain unknown. Using infectious clones of disseminating
      (Asibi) and non-disseminating (17D) yellow fever viruses (YFV), we produced
      chimeric viruses to evaluate the role of different viral genes in dissemination.
      Previously, we showed that virus produced from an infectious clone containing the
      structural genes of 17D in Asibi disseminated from the mosquito midgut at a rate
      of 31%, indicating that some genetic determinants of dissemination must lie
      within the non-structural (NS) protein genes or 3' non-coding region (NCR). We
      chose to investigate the roles of NS2A, NS4B, and the 3'NCR in YFV dissemination.
      Substitution of the 17D NS2A or NS4B into Asibi significantly attenuated YFV
      dissemination, demonstrating that this is a multigenic property. There was no
      difference in dissemination after substitution of the 17D 3'NCR.

PMID- 17172387
TI  - Characterization of Sepik and Entebbe bat viruses closely related to yellow fever
      virus.
AB  - Yellow fever virus has a special place in medical history as the first animal
      virus isolated and as the prototype virus in the genus Flavivirus, which contains
      many serious human pathogens. Only recently, its closely related viruses within
      the group were identified phylogenetically. In this study, we obtained complete
      or near complete genome sequences of two viruses most closely related to yellow
      fever virus: Sepik virus of Papua New Guinea and Entebbe bat virus of Africa.
      Based on full-genomic characterization and genomic traits among related viruses,
      we identified Sepik virus to be most closely related to yellow fever virus and
      analyzed the pattern of repeat and conserved sequence motifs in the 3'-noncoding
      region among the members of yellow fever virus cluster. We also discuss the
      geographic dispersal as a part of ecological traits of this lineage of
      flaviviruses.

PMID- 17172388
TI  - Different fecal shedding patterns of two common strains of hepatitis E virus at
      three Japanese swine farms.
AB  - Zoonotic infections caused by eating the meat of deer, wild boar, and pig have
      been suggested in Japan, a country that is not epidemic for hepatitis E caused by
      hepatitis E virus (HEV). This virus is widely spread in domestic pigs in both
      epidemic and non-epidemic countries. We studied fecal HEV shedding patterns on
      three Japanese farms that had two common genotype III HEV strains. Two of the
      three farms had high shedding peaks (75% and 100%) in pigs 1-3 months of age,
      suggesting that these animals had the highest risk of spreading HEV through
      feces. Another farm had a low shedding rate in animals six months of age and a
      low prevalence of the IgG antibody to HEV. Fecal IgA antibody to HEV was found in
      sucking pigs < 13 days of age on farms that had high and low shedding patterns. A
      small fraction of pigs (3 of 43 [7%]) at the finishing stage (5-6 months of age)
      still shed HEV on the three farms.

PMID- 17172389
TI  - In vitro activity of ferroquine (SAR97193) is independent of chloroquine
      resistance in Plasmodium falciparum.
AB  - Nowadays, chloroquine-resistant malaria appears in almost all endemic regions.
      Ferroquine is a derivative of chloroquine and shows good activity in vitro and in
      animal models, but the development of cross-resistance is of concern. We tested
      in vitro susceptibilities of Plasmodium falciparum field isolates from Gabon to
      ferroquine, chloroquine, and artesunate. As expected, chloroquine resistance was
      present in all parasite isolates (median 50% inhibitory concentration = 113
      nmol/L). Ferroquine (1.94 nmol/L) and artesunate (0.96 nmol/L) were highly
      active, and no significant correlation between any of the three drugs was
      observed. In contrast to our findings, previous studies showed an association
      between chloroquine and ferroquine activities. We could reproduce this
      association by using different initial parasitemias, but analysis of covariance
      revealed that initial parasitemia and not parasite strain was the critical
      determinant for the correlation between chloroquine and ferroquine activities. We
      conclude that ferroquine is highly active in chloroquine-resistant parasites, and
      we anticipate no enhanced selection for resistance against ferroquine in
      chloroquine-resistant parasites.

PMID- 17172390
TI  - Monitoring chloroquine resistance using Plasmodium falciparum parasites isolated
      from wild mosquitoes in Tanzania.
AB  - Monitoring antimalarial drug resistance is a useful epidemiologic tool and
      provides early detection of resistance foci. Using DNA extracted from the
      head/thorax of wild mosquitoes collected from Bagamoyo Coastal Tanzania, samples
      infected by Plasmodium falciparum (N = 89, in 2002 and N = 249 in 2004) were
      screened by nested polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP) assay for mutations at Pfcrt76 and Pfmdr1-86 associated with
      chloroquine (CQ) resistance. The majority of isolates were of single infection
      (71%), and the prevalence of mutant alleles of Pfcrt76 decreased from 64.5% in
      2002 to 16% in 2004; likewise, mutant Pfmdr1-86 alleles decreased from 46.6% to
      2.7%. Overall, there was a decline of mutant isolates by a factor of 17 and 4 for
      Pfmdr1 and Pfcrt, respectively. In contrast, isolates with wild-type alleles
      increased significantly from < 20% in 2002 to 67.6% for Pfcrt76 and 83.5% for
      Pfmdr1-86 in 2004. This observation suggest a biologic trend of decrease of CQ
      mutants and a subsequent increase of CQ susceptible parasites in circulation
      after the discontinued use of CQ in 2001 as a first-line drug in Tanzania. High
      prevalence of susceptible P. falciparum found in circulation not only supports
      other reports of a decline of mutant parasites after a reduction of drug
      selection pressure but suggests that the fitness cost is high in mutant
      parasites. Typing parasite isolates from infected mosquitoes, an alternative
      means of data collection, has the potential to increase the spatial and temporal
      coverage, and this approach is practical in highly endemic regions of Africa.

PMID- 17172391
TI  - Deaths caused by malaria in Switzerland 1988-2002.
AB  - Despite sophisticated intensive medicine, between one and three malaria
      associated deaths occur annually in Switzerland. In this retrospective study, 33
      deaths (25 men and 8 women) caused by falciparum malaria reported in Switzerland
      from 1988 to 2002 were analyzed. The case fatality ratio (CFR) for the falciparum
      infections for the 15-year period was 1.2%, with a peak of 2.2% in 1991. Sub
      Saharan Africa was the source of all the imported fatal infections. Non-immune
      Europeans had a significantly higher case fatality ratio than the non-Europeans
      (1.7% versus 0.2%; P < 0.001). Careless use or non-use of prophylaxis, sometimes
      because of physicians giving unsatisfactory pre-travel advice, and initially
      missed diagnosis post-travel were factors that contributed to the development of
      severe infections leading to death. Travelers should be sensitized to the risk of
      malaria by well-informed general practitioners. Updated information is readily
      available (www.safetravel.ch). Regarding diagnosis and treatment, greater
      physician awareness of the disease is needed, and expert advice should be sought
      without hesitation. Rapid malaria tests may be a useful diagnostic adjunct in
      centers where microscopic expertise is lacking. Falciparum malaria in a non
      immune patient is an emergency requiring immediate treatment.

PMID- 17172392
TI  - Imported Plasmodium falciparum malaria: are patients originating from disease
      endemic areas less likely to develop severe disease? A prospective, observational
      study.
AB  - Just more than 2,000 cases of Plasmodium falciparum malaria are reported in the
      United Kingdom annually, with a mortality rate of approximately 1%. Some studies
      suggest that patients with malaria who originate from disease-endemic areas are
      less likely to develop severe disease; such patients are often treated at home.
      We have prospectively examined 99 patients with imported P. falciparum malaria
      and categorized them according to severity as defined by World Health
      Organization criteria. There was no significant difference between those who
      developed severe disease and those who did not in terms of their ethnicity,
      residence in a malaria-endemic area, or history of previous episodes of malaria.
      To assume a patient has clinical immunity to malaria simply because they
      originate from or have lived for a long time in a malaria-endemic area may be
      inappropriate and unsafe.

PMID- 17172393
TI  - Re-ingestion of Plasmodium berghei sporozoites after delivery into the host by
      mosquitoes.
AB  - Malaria-infected mosquitoes feeding on a mammalian host inject sporozoites into
      the skin to induce a malaria infection. The numbers of sporozoites ultimately
      able to reach the liver may be important determinants of the characteristics of
      the ensuing blood infection. Because feeding mosquitoes not only inject
      sporozoites into the host but concomitantly ingest blood to obtain their
      bloodmeal, some sporozoites are re-ingested by the feeding mosquito. We studied
      transmission of fluorescent Plasmodium berghei sporozoites injected into mice by
      Anopheles stephensi mosquitoes and found that the numbers of sporozoites re
      ingested by mosquitoes are comparable to numbers previously reported to be
      delivered directly into mice. Thus, re-ingestion of sporozoites likely plays a
      significant role in transmission dynamics of malaria by mosquitoes, and may
      account for the failure of some sporozoite-infected mosquitoes to induce a blood
      infection.

PMID- 17172394
TI  - Sensitivity and specificity of an antigen detection ELISA for malaria diagnosis.
AB  - Enzyme-linked immunosorbent assays (ELISAs) allow for the testing of large
      numbers of samples within a short time frame. We tested the sensitivity and
      specificity of a histidine-rich protein 2 (HRP2)-based, commercially available
      ELISA antigen detection assay for Plasmodium falciparum (Malaria Antigen CELISA;
      Cellabs, Sydney, Australia). A total of 700 whole blood samples obtained from
      symptomatic outpatients of malaria clinics along the Thai-Myanmar border were
      tested relative to blinded duplicate expert microscopy adjusted with species
      specific polymerase chain reaction (PCR). PCR-adjusted microscopy showed that 79
      (11.3%) were infected with P. falciparum, 118 (16.9%) with P. vivax, 1 (0.1%)
      with P. malariae, 7 (1.0%) with mixed infections (P. falciparum and P. vivax),
      and 495 (70.7%) were negative. The geometric mean parasite density for P.
      falciparum was 7547/muL (range: 12-363,810/muL). The overall sensitivity of the
      HRP2 ELISA for P. falciparum malaria was 98.8% (95% CI, 93.6-100%) and the
      specificity was 100% (95% CI, 99.5-100%). The positive and negative predictive
      values for the ELISA were 100% (95% CI, 96.5-100%) and 99.8% (95% CI, 99.1-100%),
      respectively. The results for P. falciparum were clearly superior to expert
      microscopy alone, particularly in mixed infections. Microscopy combined with
      ELISA reaches a sensitivity and specificity similar to PCR-adjusted microscopy
      for the diagnosis of P. falciparum while being considerably less expensive and
      faster. We conclude that ELISA serves as an excellent tool to augment microscopy
      as the gold standard for P. falciparum diagnosis in research settings and should
      be further evaluated for screening in blood banks.

PMID- 17172395
TI  - Evaluation of three rapid tests for diagnosis of P. falciparum and P. vivax
      malaria in Colombia.
AB  - The diagnostic capacity of three malaria rapid diagnostic tests (RDTs), NOW
      Malaria-ICT, OptiMAL-IT, and Paracheck-Pf, was evaluated against expert
      microscopy in Colombia. We tested 896 patients, of whom microscopy confirmed 139
      P. falciparum, 279 P. vivax, and 13 mixed P.f/P.v infections and 465 negatives.
      Paracheck-Pf and NOW-malaria-ICT were more accurate in detecting P. falciparum
      (sensitivities 90.8% and 90.1%, respectively) in comparison with Optimal-IT
      (83.6%). NOW showed an acceptable Pf detection rate at low densities (<
      500/microL), but resulted in a higher proportion of false positives. For P. vivax
      diagnosis, Optimal-IT had a higher sensitivity than NOW (91.0% and 81.4%,
      respectively). The choice between the two Pf/Pv detecting RDTs balances P.
      falciparum and P. vivax detection rates. Considering some degree of P. falciparum
      overtreatment and failure to detect all P. vivax cases as more acceptable than
      missing some cases of P. falciparum, we recommend careful implementation of NOW
      malaria-ICT in areas where microscopy is lacking. The price is however still a
      constraint.

PMID- 17172396
TI  - Epidemiology and spatial analysis of malaria in the Northern Peruvian Amazon.
AB  - A retrospective surveillance study was conducted to examine the micro-geographic
      variation of malaria incidence in three malaria-endemic communities in the
      Northern Peruvian Amazon. The annual malaria risk rate (per 100) ranged from 38%
      to 47% for Plasmodium vivax and from 15% to 18% for P. falciparum. Spatial
      clusters were found for P. vivax in Padre Cocha, Manacamiri, and Zungaro Cocha,
      and for P. falciparum only in Padre Cocha. Spatial-temporal clusters showed that
      the highest monthly number of P. vivax cases varied every year from December to
      March in 1996-1997 and from February to June in 1998-1999, and for P. falciparum
      from November to April in 1996-1997 and from January to April in 1998-1999. Our
      results suggest a constant presence of high-risk areas (hot spots) for malaria
      infection in periods with high or low malaria incidence. Modest targeted control
      efforts directed at identified high-risk areas may have significant impact on
      malaria transmission in this region.

PMID- 17172397
TI  - Urban farming and malaria risk factors in a medium-sized town in Cote d'Ivoire.
AB  - Urbanization occurs at a rapid pace across Africa and Asia and affects people's
      health and well-being. A typical feature in urban settings of Africa is the
      maintenance of traditional livelihoods, including agriculture. The purpose of
      this study was to investigate malaria risk factors in urban farming communities
      in a medium-sized town in Cote d'Ivoire. Two cross-sectional surveys were carried
      out among 112 households from six agricultural zones. First, the heads of
      households were interviewed on agricultural land use, farming practices, water
      storage, sanitation facilities, and socioeconomic status. Second, a finger prick
      blood sample was taken from all household members and examined for the occurrence
      and density of Plasmodia. Geographic coordinates of houses, farming plots, and
      potential mosquito breeding sites were recorded and integrated into a geographic
      information system. Predictors of Plasmodium falciparum parasitemia were assessed
      using non-random and random effects Bayesian regression models. The overall
      prevalence of P. falciparum was 32.1%. In children < 15 years of age, risk
      factors for a P. falciparum infection included living in a specific agricultural
      zone, close proximity to permanent ponds and fish ponds, periodic stays overnight
      in temporary farm huts, and low socioeconomic status. Our findings indicate that
      specific crop systems and specific agricultural practices may increase the risk
      of malaria in urban settings of tropical Africa.

PMID- 17172398
TI  - Myocarditis in West Nile Virus infection.
AB  - West Nile virus (WNV) myocarditis has been documented pathologically in birds and
      mammals but has rarely been reported in human clinical syndromes. We describe
      myocarditis associated with WNV.

PMID- 17172399
TI  - Trichomonas empyema with respiratory failure.
AB  - Pulmonary trichomoniasis is rare, and few cases of trichomonas empyema have been
      reported in the literature. We describe a rare case of a non-immunocompromised 55
      year-old man with Trichomonas empyema presenting with bilateral pleural effusion
      leading to respiratory failure. Examination of the pleural effusion showed
      numerous motile organisms by fresh wet preparation that were identified as
      Trichomonas species by Liu stain. The patient was successfully treated with
      metronidazole, ampicillin/clavunalate, fibrinolytic therapy, and thoracotomy
      decortication.

PMID- 17172400
TI  - Discovery and development of anticancer aptamers.
AB  - Aptamers, also termed as decoys or "chemical antibodies," represent an emerging
      class of therapeutics. They are short DNA or RNA oligonucleotides or peptides
      that assume a specific and stable three-dimensional shape in vivo, thereby
      providing specific tight binding to protein targets. In some cases and as opposed
      to antisense oligonucleotides, effects can be mediated against extracellular
      targets, thereby preventing a need for intracellular transportation. The first
      aptamer approved for use in man is a RNA-based molecule (Macugen, pegaptanib)
      that is administered locally (intravitreally) to treat age-related macular
      degeneration by targeting vascular endothelial growth factor. The most advanced
      aptamer in the cancer setting is AS1411, formerly known as AGRO100, which is
      being administered systemically in clinical trials. AS1411 is a 26-mer unmodified
      guanosine-rich oligonucleotide, which induces growth inhibition in vitro, and has
      shown activity against human tumor xenografts in vivo. The mechanism underlying
      its antiproliferative effects in cancer cells seems to involve initial binding to
      cell surface nucleolin and internalization, leading to an inhibition of DNA
      replication. In contrast to other unmodified oligonucleotides, AS1411 is
      relatively stable in serum-containing medium, probably as a result of the
      formation of dimers and a quartet structure. In a dose escalation phase I study
      in patients with advanced solid tumors, doses up to 10 mg/kg/d (using a four or
      seven continuous infusion regime) have been studied. Promising signs of activity
      have been reported (multiple cases of stable disease and one near complete
      response in a patient with renal cancer) in the absence of any significant
      adverse effects. Further trials are ongoing in renal and non-small cell lung
      cancers. In preclinical studies, additional aptamers have been described against
      several cancer targets, such as tenascin-C, the transcription factor signal
      transducer and activator of transcription 3, and antiapoptotic and Ku proteins.

PMID- 17172402
TI  - Blockade of transforming growth factor-beta-activated kinase 1 activity enhances
      TRAIL-induced apoptosis through activation of a caspase cascade.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a
      member of the TNF-alpha ligand family that selectively induces apoptosis in a
      variety of tumor cells. To clarify the molecular mechanism of TRAIL-induced
      apoptosis, we focused on transforming growth factor-beta-activated kinase 1
      (TAK1) mitogen-activated protein kinase (MAPK) kinase kinase, a key regulator of
      the TNF-alpha-induced activation of p65/RelA and c-Jun NH2-terminal kinase/p38
      MAPKs. In human cervical carcinoma HeLa cells, TRAIL induced the delayed
      phosphorylation of endogenous TAK1 and its activator protein TAB1 and TAB2, which
      contrasted to the rapid response to TNF-alpha. Specific knockdown of TAK1 using
      small interfering RNA (siRNA) abrogated the TRAIL-induced activation of p65 and c
      Jun NH2-terminal kinase/p38 MAPKs. TRAIL-induced apoptotic signals, including
      caspase-8, caspase-3, caspase-7, and poly(ADP-ribose) polymerase, were enhanced
      by TAK1 siRNA. Flow cytometry showed that the binding of Annexin V to cell
      surface was also synergistically increased by TRAIL in combination with TAK1
      siRNA. In addition, pretreatment of cells with 5Z-7-oxozeaenol, a selective TAK1
      kinase inhibitor, enhanced the TRAIL-induced cleavage of caspases and binding of
      Annexin V. The TAK1-mediated antiapoptotic effects were also observed in human
      lung adenocarcinoma A549 cells. In contrast, TAK1-deficient mouse embryonic
      fibroblasts are resistant to TRAIL-induced apoptosis, and treatment of control
      mouse embryonic fibroblasts with 5Z-7-oxozeaenol did not drastically promote the
      TRAIL-induced activation of a caspase cascade. These results suggest that TAK1
      plays a critical role for TRAIL-induced apoptosis, and the blockade of TAK1
      kinase will improve the chances of overcoming cancer.

PMID- 17172403
TI  - Enhancement of Apo2L/TRAIL-mediated cytotoxicity in esophageal cancer cells by
      cisplatin.
AB  - Although expressing adequate levels of functional tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, significant proportion of
      cancer cells exhibit resistance to the cytotoxic effect of this ligand. Exposure
      of Apo2L/TRAIL-refractory cancer cells to cytotoxic chemotherapeutic agents
      enhances their sensitivity to Apo2L/TRAIL cytotoxicity. This study aims to
      elucidate the molecular mechanism responsible for the cisplatin-mediated
      enhancement of Apo2L/TRAIL sensitivity in cultured esophageal cancer cells.
      Exposure of cancer cells to sublethal concentrations of cisplatin resulted in
      profound potentiation of their susceptibility to Apo2L/TRAIL cytotoxicity as
      indicated by 2- to >20-fold reduction in Apo2L/TRAIL IC50 values. Significant
      activation of caspase-8, caspase-9, and caspase-3 was observed only in cells
      treated with cisplatin/Apo2L/TRAIL combination and not in those exposed to either
      agent alone. More importantly, activation of these key caspases was significantly
      abrogated by overexpression of Bcl2 or by the selective caspase-9 inhibitor. This
      observation strongly suggested that caspase-8 activation in cells treated with
      the cisplatin/Apo2L/TRAIL combination was secondary to the mitochondria-mediated
      amplification feedback loop and activation of the executioner caspase-3 was
      dependent on the recruitment of the intrinsic pathway characteristic of the type
      II cell. Profound combination-mediated cytotoxicity and induction of apoptosis
      was completely suppressed either by Bcl2 overexpression or by inhibition of
      caspase-9 activity, which conclusively pointed to the essential role of the
      mitochondria-dependent death signaling cascade in this process. Cisplatin
      sensitizes esophageal cancer cells to Apo2L/TRAIL cytotoxicity by potentiation of
      the mitochondria-dependent death signaling pathway that leads to amplification of
      caspase activation, particularly caspase-8, by the feedback loop to efficiently
      induce apoptosis.

PMID- 17172401
TI  - Spindle checkpoint function and cellular sensitivity to antimitotic drugs.

PMID- 17172404
TI  - In silico design, synthesis, and biological evaluation of radioiodinated
      quinazolinone derivatives for alkaline phosphatase-mediated cancer diagnosis and
      therapy.
AB  - As part of the development of enzyme-mediated cancer imaging and therapy, a novel
      technology to entrap water-insoluble radioactive molecules within solid tumors,
      we show that a water-soluble, radioactive quinazolinone prodrug, ammonium 2-(2'
      phosphoryloxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ(2-P)), is
      hydrolyzed by alkaline phosphatase to a water-insoluble, radiolabeled drug, 2-(2'
      hydroxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ(2-OH)). Biodistribution
      data suggest the existence of two isoforms of the prodrug (IQ(2-P(I)) and IQ(2
      P)), and this has been confirmed by their synthesis and characterization.
      Structural differences of the two isoforms have been examined using in silico
      molecular modeling techniques and docking methods to describe the
      interaction/binding between the isoforms and human placental alkaline phosphatase
      (PLAP), a tumor cell, membrane-associated, hydrolytic enzyme whose structure is
      known by X-ray crystallographic determination. Docking data show that IQ(2-P),
      but not IQ(2-P(I)), fits the active binding site of PLAP favorably and interacts
      with the catalytic amino acid Ser(92), which plays an important role in the
      hydrolytic process. The binding free energies (DeltaG(binding)) of the isoforms
      to PLAP predict that IQ(2-P) will be the better substrate for PLAP. The in vitro
      incubation of the isoforms with PLAP leads to the rapid hydrolysis of IQ(2-P)
      only and confirms the in silico expectations. Fluorescence microscopy shows that
      in vitro incubation of IQ(2-P) with mouse and human tumor cells causes the
      extracellular, alkaline phosphatase-mediated hydrolysis of the molecule and
      precipitation of fluorescent crystals of IQ(2-OH). No hydrolysis is seen in the
      presence of normal mouse and human cells. Furthermore, the intratumoral injection
      of 125IQ(2-P) into alkaline phosphatase-expressing solid human tumors grown s.c.
      in nude rats results in efficient hydrolysis of the compound and retention of
      approximately 70% of the injected radioactivity, whereas similar injection into
      normal tissues (e.g., muscle) does not produce any measurable hydrolysis
      (approximately 1%) or retention of radioactivity at the injected site. These
      studies support the enzyme-mediated cancer imaging and therapy technology and
      show the potential of such quinazolinone derivatives in the in vivo
      radiodetection (123I/124I) and therapy (131I) of solid tumors.

PMID- 17172405
TI  - Cooperative action of tamoxifen and c-Src inhibition in preventing the growth of
      estrogen receptor-positive human breast cancer cells.
AB  - It has long been appreciated that estrogenic signaling contributes to breast
      cancer progression. c-Src is also required for a number of processes involved in
      tumor progression and metastasis. We have previously identified the K303R mutant
      estrogen receptor alpha (ERalpha) that confers hypersensitivity to low levels of
      estrogen. Because ERalpha and c-Src have been shown to interact in a number of
      different systems, we wanted to evaluate the role of c-Src kinase in estrogen
      stimulated growth and survival of ERalpha-positive breast cancer cells. MCF-7
      cells stably expressing the mutant receptor showed increased c-Src kinase
      activity and c-Src tyrosine phosphorylation when compared with wild-type ERalpha
      expressing cells. A c-Src inhibitor, AZD0530, was used to analyze the biological
      effects of pharmacologically inhibiting c-Src kinase activity. MCF-7 cells showed
      an anchorage-dependent growth IC50 of 0.47 micromol/L, which was increased 4-fold
      in the presence of estrogen. In contrast, cells stably expressing the mutant
      ERalpha had an elevated IC50 that was only increased 1.4-fold by estrogen
      stimulation. The c-Src inhibitor effectively inhibited the anchorage-independent
      growth of both of these cells, and estrogen was able to reverse these effects.
      When cells were treated with suboptimal concentrations of c-Src inhibitor and
      tamoxifen, synergistic inhibition was observed, suggesting a cooperative
      interaction between c-Src and ERalpha. These data clearly show an important role
      for ERalpha and estrogen signaling in c-Src-mediated breast cancer cell growth
      and survival. Here, we show that c-Src inhibition is blocked by estrogen
      signaling; thus, the therapeutic use of c-Src inhibitors may require inhibition
      of ERalpha in estrogen-dependent breast cancer.

PMID- 17172406
TI  - Combination therapy with IFN-alpha plus bortezomib induces apoptosis and inhibits
      angiogenesis in human bladder cancer cells.
AB  - In a recent study, we showed that the proteasome inhibitor bortezomib sensitizes
      human bladder cancer cells to IFN-induced cell death. Here, we characterized the
      molecular mechanisms underlying the antitumoral effects of the combination in
      more detail. Bortezomib synergized with IFN-alpha to promote apoptosis via a
      tumor necrosis factor-related apoptosis-inducing ligand-associated mechanism but
      did not inhibit production of proangiogenic factors (vascular endothelial growth
      factor, basic fibroblast growth factor, and interleukin-8) in human UM-UC-5
      cells. In contrast, exposure to the combination did not increase the levels of
      apoptosis in human UM-UC-3 cells but did inhibit the production of basic
      fibroblast growth factor and vascular endothelial growth factor. Studies with
      tumor xenografts confirmed that combination therapy with bortezomib plus IFN
      alpha was effective in both models but that the effects were associated with
      differential effects on tumor necrosis factor-related apoptosis-inducing ligand
      associated apoptosis (predominant in UM-UC-5) versus inhibition of angiogenesis
      (predominant in UM-UC-3). Together, our results show that combination therapy
      with IFN-alpha plus bortezomib is effective but can work via different mechanisms
      (apoptosis versus angiogenesis inhibition) in preclinical models of human bladder
      cancer.

PMID- 17172407
TI  - Comparison of biochemical and biological effects of ML858 (salinosporamide A) and
      bortezomib.
AB  - Strains within the genus Salinospora have been shown to produce complex natural
      products having antibiotic and antiproliferative activities. The biochemical
      basis for the cytotoxic effects of salinosporamide A has been linked to its
      ability to inhibit the proteasome. Synthetically accessible salinosporamide A
      (ML858) was used to determine its biochemical and biological activities and to
      compare its effects with those of bortezomib. ML858 and bortezomib show time- and
      concentration-dependent inhibition of the proteasome in vitro. However, unlike
      bortezomib, which is a reversible inhibitor, ML858 covalently binds to the
      proteasome, resulting in the irreversible inhibition of 20S proteasome activity.
      ML858 was equipotent to bortezomib in cell-based reporter stabilization assays,
      but due to intramolecular instability is less potent in long-term assays. ML858
      failed to maintain levels of proteasome inhibition necessary to achieve efficacy
      in tumor models responsive to bortezomib. Our results show that ML858 and
      bortezomib exhibit different kinetic and pharmacologic profiles and suggest that
      additional characterization of ML858 is warranted before its therapeutic
      potential can be fully appreciated.

PMID- 17172408
TI  - Glucocorticoid receptor transcriptional isoforms and resistance in multiple
      myeloma cells.
AB  - Although glucocorticoids play an important role in the treatment of multiple
      myeloma, some patients do not respond or develop resistance. The glucocorticoid
      receptor (GR), a single gene, mediates the effects of glucocorticoids. Using a
      model system of a multiple myeloma cell line sensitive to glucocorticoids and its
      early and late resistant variants, we have analyzed mutations in the GR gene,
      detected the presence of different transcriptional isoforms, quantified their
      levels of expression, and identified the promoters that regulate their
      expression. Levels of GR transcripts were comparable with the expression of total
      GR protein. Development of resistance correlates with an overall reduction in GR
      mRNA levels. This decrease in GR levels is neither due to mutation of the gene
      nor due to methylation. GRalpha is the predominant isoform in the sensitive cell
      line decreasing in expression in the early resistant cells and virtually
      undetectable in late resistant cells. GR-P is expressed at equivalent levels in
      both sensitive and early resistant cells, whereas in the late resistant cells, GR
      P is the predominant isoform. GR-A is only expressed in the early resistant cell
      line. GRbeta is the least expressed isoform in all cell lines. Interestingly, the
      level of expression of exon 1-exon 2 RNA fragments remains similar in sensitive
      and resistant cell lines. Resistant cells became sensitive to glucocorticoids
      after GRalpha transfection. In conclusion, we show different patterns of
      expression of the GR isoforms and provide evidence that a decline in the
      expression of GRalpha may be associated with development of resistance.

PMID- 17172409
TI  - Inhibition of phosphatidylinositol-3-kinase and mitogen-activated protein kinase
      kinase 1/2 prevents melanoma development and promotes melanoma regression in the
      transgenic TPRas mouse model.
AB  - A number of human melanomas show hyperactivation of the Ras pathway due to
      mutations of the molecule or alteration of upstream or downstream effectors. In
      this study, we evaluated the effect of blocking the two Ras downstream pathways
      phosphatidylinositol-3-kinase/Akt and Raf/mitogen-activated protein kinase
      kinase/extracellular signal-regulated kinase on melanoma development and
      regression in the TPRas mouse model. The inhibition of these two signaling
      cascades by topically applied Ly294002 and U0126 significantly delayed melanoma
      development and significantly decreased the tumor incidence, particularly when
      the drugs were applied in combination. Treatment with the inhibitors of
      established melanomas resulted in complete remission in 33% of mice and partial
      regression in 46% of mice when drugs were delivered in combination. These
      responses correlated with increased apoptosis and decreased proliferation both in
      vitro and in vivo and reduced tumor angiogenesis. In conclusion, this study
      strongly supports the role of the phosphatidylinositol-3-kinase/Akt and
      Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase
      pathways in the development and maintenance of Ras-dependent melanomas and
      supports the notion that specific inhibition of these effectors may represent a
      very promising avenue for the treatment and prevention of the disease.

PMID- 17172410
TI  - Association of insulin-like growth factor binding protein-3 expression with
      melanoma progression.
AB  - Previous studies from our laboratory have identified several endothelial cell
      associated marker genes implicated in human melanoma metastasis via tumor
      vasculogenic mimicry. In this study, we used dual model systems composed of
      melanoma cell lines and clinical melanoma samples to validate the importance of
      insulin-like growth factor binding protein-3 (IGFBP-3) as a marker involved in
      disease progression. Gene expression analysis was done using a microarray
      approach for both primary and metastatic melanoma samples. The expression of
      IGFBP-3 was decreased using a small interfering RNA (siRNA) knockdown approach
      and quantified with real-time quantitative reverse transcription-PCR analysis.
      The expression of insulin-like growth factor binding protein 3 (IGFBP-3) was up
      regulated by nearly 16-fold in WM266-4 compared with WM35 cells. A subsequent
      parallel analysis using freshly isolated primary and metastatic melanoma cell
      samples and melanoma tissue array confirmed the previous findings. The functional
      significance of IGFBP-3 in melanoma invasion was further investigated using a
      siRNA gene knockdown approach, with the expression of IGFBP-3 markedly reduced.
      Additionally, siRNA knockdown resulted in a significant reduction in cell
      motility, migration, and invasive capacity of WM266-4 cells in vitro. These
      results strongly suggest that IGFBP-3 expression may be a vital cell motility,
      migration, and proliferation factor necessary for melanoma metastasis and is an
      important biomarker in human melanoma.

PMID- 17172411
TI  - Histone deacetylase inhibitor enhances 5-fluorouracil cytotoxicity by down
      regulating thymidylate synthase in human cancer cells.
AB  - Thymidylate synthase (TS) overexpression is a key determinant of 5-fluorouracil
      (5-FU) resistance in human cancer cells. TS is also acutely up-regulated with 5
      FU treatment, and, thus, novel strategies targeting TS down-regulation seem to be
      promising in terms of modulating 5-FU resistance. Here, we report that histone
      deacetylase inhibitors can reverse 5-FU resistance by down-regulating TS. By
      using cDNA microarrays and validation experiments, we found that trichostatin A
      reduced the expression of both TS mRNA and TS protein. Cotreatment with
      trichostatin A and cycloheximide restored TS mRNA expression, suggesting that TS
      mRNA is repressed through new protein synthesis. On the other hand, TS protein
      expression was significantly reduced by lower doses of trichostatin A (50
      nmol/L). Mechanistically, TS protein was found to interact with heat shock
      protein (Hsp) complex, and trichostatin A treatment induced chaperonic Hsp90
      acetylation and subsequently enhanced Hsp70 binding to TS, which led to the
      proteasomal degradation of TS protein. Of note, combined treatment with low-dose
      trichostatin A and 5-FU enhanced 5-FU-mediated cytotoxicity in 5-FU-resistant
      cancer cells in accordance with TS protein down-regulation. We conclude that a
      combinatorial approach using histone deacetylase inhibitors may be useful at
      overcoming 5-FU resistance.

PMID- 17172412
TI  - Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated
      polycomb repressive complex 2 proteins in human acute leukemia cells.
AB  - Human enhancer of zeste 2 (EZH2) protein belongs to the multiprotein polycomb
      repressive complex 2, which also includes suppressor of zeste 12 (SUZ12) and
      embryonic ectoderm development (EED). The polycomb repressive complex 2 complex
      possesses histone methyltransferase activity mediated by the Su(var)3-9, enhancer
      of zeste, and trithorax domain of EZH2, which methylates histone H3 on lysine (K)
      27 (H3K27). In the present studies, we determined that treatment with the
      hydroxamate histone deacetylase inhibitor LBH589 or LAQ824 depleted the protein
      levels of EZH2, SUZ12, and EED in the cultured (K562, U937, and HL-60) and
      primary human acute leukemia cells. This was associated with decreased levels of
      trimethylated and dimethylated H3K27, with concomitant depletion of the homeobox
      domain containing HOXA9 and of MEIS1 transcription factors. Knockdown of EZH2 by
      EZH2 small interfering RNA also depleted SUZ12 and EED, inhibited histone
      methyltransferase activity, and reduced trimethylated and dimethylated H3K27
      levels, with a concomitant loss of clonogenic survival of the cultured acute
      myelogenous leukemia (AML) cells. EZH2 small interfering RNA sensitized the AML
      cells to LBH589-mediated depletion of EZH2, SUZ12, and EED; loss of clonogenic
      survival; and LBH589-induced differentiation of the AML cells. These findings
      support the rationale to test anti-EZH2 treatment combined with hydroxamate
      histone deacetylase inhibitors as an antileukemia epigenetic therapy, especially
      against AML with coexpression of EZH2, HOXA9, and MEIS1 genes.

PMID- 17172413
TI  - Growth inhibition and induction of apoptosis in acute myeloid leukemia cells by
      new indolinone derivatives targeting fibroblast growth factor, platelet-derived
      growth factor, and vascular endothelial growth factor receptors.
AB  - In acute myeloid leukemia (AML), receptor tyrosine kinase ligands promote growth
      and survival and contribute to AML-associated marrow neoangiogenesis. We have
      tested simultaneous inhibition of vascular endothelial growth factor, fibroblast
      growth factor, and platelet-derived growth factor receptor signaling by novel
      indolinone derivatives using 14 myeloid, including 11 human leukemic, cell lines.
      Compounds inhibited colony formation of all cell lines in a dose-dependent
      fashion. Inhibitory concentrations for 50% of the colony formation/survival
      (IC50) for BIBF1000 were <100 nmol/L for 3 of 11, <or=500 nmol/L for 6 of 11, and
      <1,000 nmol/L for 10 of 11 leukemic cell lines, with one cell line being
      resistant in the dose range <1,000 nmol/L. BIBF1120 was less effective with 4 of
      11 leukemic cell lines being resistant within the dose range <1,000 nmol/L.
      Testing of myeloid 32D cells transfected with empty vector, wild-type Flt3, or
      Flt3 carrying an internal tandem duplication mutation revealed higher resistance
      for the internal tandem duplication mutant. These effects of the compounds were
      associated with inhibition of tyrosine phosphorylation and the mitogen-activated
      protein kinase pathway. Furthermore, both compounds induced apoptosis in the
      sensitive cell lines. In Mono-Mac1 cells, the compounds had a direct proapoptotic
      effect that was increasing the proapoptotic effect of 1-beta-D
      arabinofuranosylcytosine. The data provide a rationale for clinical evaluation of
      these tyrosine kinase inhibitors in AML.

PMID- 17172414
TI  - Inhibition of CXCR4 with the novel RCP168 peptide overcomes stroma-mediated
      chemoresistance in chronic and acute leukemias.
AB  - The chemokine receptor CXCR4 mediates the migration of hematopoietic cells to the
      stroma-derived factor 1alpha (SDF-1alpha)-producing bone marrow microenvironment.
      Using peptide-based CXCR4 inhibitors derived from the chemokine viral macrophage
      inflammatory protein II, we tested the hypothesis that the inhibition of CXCR4
      increases sensitivity to chemotherapy by interfering with stromal/leukemia cell
      interactions. First, leukemic cells expressing varying amounts of surface CXCR4
      were examined for their chemotactic response to SDF-1alpha or stromal cells,
      alone or in the presence of different CXCR4 inhibitors. Results showed that the
      polypeptide RCP168 had the strongest antagonistic effect on the SDF-1alpha- or
      stromal cell-induced chemotaxis of leukemic cells. Furthermore, RCP168 blocked
      the binding of anti-CXCR4 monoclonal antibody 12G5 to surface CXCR4 in a
      concentration-dependent manner and inhibited SDF-1alpha-induced AKT and
      extracellular signal-regulated kinase phosphorylation. Finally, RCP168
      significantly enhanced chemotherapy-induced apoptosis in stroma-cocultured
      Jurkat, primary chronic lymphocytic leukemia, and in a subset of acute
      myelogenous leukemia cells harboring Flt3 mutation. Equivalent results were
      obtained with the small-molecule CXCR4 inhibitor AMD3465. Our data therefore
      suggest that the SDF-1alpha/CXCR4 interaction contributes to the resistance of
      leukemia cells to chemotherapy-induced apoptosis. Disruption of these
      interactions by the peptide CXCR4 inhibitor RCP168 represents a novel strategy
      for targeting leukemic cells within the bone marrow microenvironment.

PMID- 17172415
TI  - Direct targeting of alphavbeta3 integrin on tumor cells with a monoclonal
      antibody, Abegrin.
AB  - The humanized monoclonal antibody Abegrin, currently in phase II trials for
      treatment of solid tumors, specifically recognizes the integrin alphavbeta3. Due
      to its high expression on mature osteoclasts, angiogenic endothelial cells, and
      tumor cells, integrin alphavbeta3 functions in several pathologic processes
      important to tumor growth and metastasis. Targeting of this integrin with Abegrin
      results in antitumor, antiangiogenic, and antiosteolytic activities. Here, we
      exploit the species specificity of Abegrin to evaluate the effects of direct
      targeting of tumor cells (independent of targeting of endothelia or osteoclasts).
      Flow cytometry analysis of human tumor cell lines shows high levels of
      alphavbeta3 on many solid tumors, including cancers of the prostate, skin, ovary,
      kidney, lung, and breast. We also show that tumor growth of alphavbeta3
      expressing tumor cells is inhibited by Abegrin in a dose-dependent manner. We
      present a novel finding that high-dose administration can actively impair the
      antitumor activity of Abegrin. We also provide evidence that antibody-dependent
      cellular cytotoxicity contributes to in vitro and in vivo antitumor activity.
      Finally, it was observed that peak biological activity of Abegrin arises at serum
      levels that are consistent with those achieved in clinical trials. These results
      support a concept that Abegrin can be used to achieve selective targeting of the
      many tumor cells that express alphavbeta3 integrin. In combination with the well
      established concept that alphavbeta3 plays a key role in cancer-associated
      angiogenesis and osteolytic activities, this triad of activity could provide new
      opportunities for therapeutic targeting of cancer.

PMID- 17172416
TI  - Terbinafine inhibits endothelial cell migration through suppression of the Rho
      mediated pathway.
AB  - We showed previously that terbinafine, an allylamine with fungicidal activity,
      could inhibit angiogenesis by suppressing the endothelial cell proliferation. In
      the present study, we further showed that terbinafine (0-120 micromol/L) dose
      dependently inhibited the adhesion and migration of human umbilical vascular
      endothelial cells (HUVEC). Western blot analysis showed that terbinafine
      decreased the levels of Ras protein and membrane-bound RhoA protein. Moreover,
      the terbinafine-induced migration inhibition in HUVEC was prevented by
      pretreatment with farnesol or geranylgeraniol. Pretreatment of HUVEC with Ras
      inhibitor peptide or a ROCK (a kinase associated with RhoA for transducing RhoA
      signaling) inhibitor, Y27632, abolished the farnesol- or geranylgeraniol-induced
      prevention effect on the terbinafine-induced migration inhibition, respectively.
      These data suggest that the consuming or depletion of geranylgeranyl
      pyrophosphate and consequent suppression of protein geranylgeranylation and
      farnesylation, which is essential for activation of Rho GTPases and Ras,
      respectively, might account for the terbinafine-induced inhibition of HUVEC
      migration. The levels of phosphorylated focal adhesion kinase and paxillin
      protein and the mRNA levels of matrix metalloproteinase-2 and matrix
      metalloproteinase-9 were also decreased by terbinafine treatment. Taken together,
      these results indicate that suppression of Rho-mediated pathway might be involved
      in the signal transduction leading to the inhibition of cell migration caused by
      terbinafine in HUVEC.

PMID- 17172417
TI  - Topoisomerase II and tubulin inhibitors both induce the formation of apoptotic
      topoisomerase I cleavage complexes.
AB  - Topoisomerase I (Top1) is a ubiquitous enzyme that removes DNA supercoiling
      generated during transcription and replication. Top1 can be trapped on DNA as
      cleavage complexes by the anticancer drugs referred to as Top1 inhibitors as well
      as by alterations of the DNA structure. We reported recently that Top1 cleavage
      complexes (Top1cc) are trapped during apoptosis induced by arsenic trioxide and
      staurosporine. In the present study, we generalize the occurrence of apoptotic
      Top1cc in response to anticancer drugs, which by themselves do not directly
      interact with Top1: the topoisomerase II inhibitors etoposide, doxorubicin, and
      amsacrine, and the tubulin inhibitors vinblastine and Taxol. In all cases, the
      Top1cc form in the early phase of apoptosis and persist throughout the apoptotic
      process. Their formation is prevented by the caspase inhibitor benzyloxycarbonyl
      Val-Ala-DL-Asp(OMe)-fluoromethylketone and the antioxidant N-acetyl-L-cysteine.
      We propose that the trapping of Top1cc is a general process of programmed cell
      death, which is caused by alterations of the DNA structure (oxidized bases and
      strand breaks) induced by caspases and reactive oxygen species.

PMID- 17172418
TI  - The endothelial cytoskeleton as a target of electroporation-based therapies.
AB  - Electroporation-based therapies, such as electrochemotherapy and electrogene
      therapy, result in the disruption of blood vessel networks in vivo and cause
      changes in blood flow and vascular permeability. The effects of electroporation
      on the cytoskeleton of cultured primary endothelial cells and on endothelial
      monolayer permeability were investigated to elucidate possible mechanisms
      involved. Human umbilical vein endothelial cells (HUVECs) were electroporated in
      situ and then immunofluorescence staining for filamentous actin, beta-tubulin,
      vimentin, and VE-cadherin as well as Western blotting analysis of levels of
      phosphorylated myosin light chain and cytoskeletal proteins were performed.
      Endothelial permeability was determined by monitoring the passage of FITC-coupled
      dextran through endothelial monolayers. Exposure of endothelial cells to electric
      pulses resulted in a profound disruption of microfilament and microtubule
      cytoskeletal networks, loss of contractility, and loss of vascular endothelial
      cadherin from cell-to-cell junctions immediately after electroporation. These
      effects were voltage dependent and reversible because cytoskeletal structures
      recovered within 60 min of electroporation with up to 40 V, without any
      significant loss of cell viability. The cytoskeletal effects of electroporation
      were paralleled by a rapid increase in endothelial monolayer permeability. These
      results suggest that the remodeling of the endothelial cytoskeleton and changes
      in endothelial barrier function could contribute to the vascular disrupting
      actions of electroporation-based therapies and provide an insight into putative
      mechanisms responsible for the observed increase in permeability and cessation of
      blood flow in vivo.

PMID- 17172419
TI  - Fanconi anemia D2 protein confers chemoresistance in response to the anticancer
      agent, irofulven.
AB  - The Fanconi anemia-BRCA pathway of genes are frequently mutated or epigenetically
      repressed in human cancer. The proteins of this pathway play pivotal roles in DNA
      damage signaling and repair. Irofulven is one of a new class of anticancer agents
      that are analogues of mushroom-derived illudin toxins. Preclinical studies and
      clinical trials have shown that irofulven is effective against several tumor cell
      types. The exact nature of irofulven-induced DNA damage is not completely
      understood. Previously, we have shown that irofulven activates ATM and its
      targets, NBS1, SMC1, CHK2, and p53. In this study, we hypothesize that irofulven
      induces DNA double-strand breaks and FANCD2 may play an important role in
      modulating cellular responses and chemosensitivity in response to irofulven
      treatment. By using cells that are proficient or deficient for FANCD2, ATR, or
      ATM, we showed that irofulven induces FANCD2 monoubiquitination and nuclear foci
      formation. ATR is important in mediating irofulven-induced FANCD2
      monoubiquitination. Furthermore, we showed that FANCD2 plays a critical role in
      maintaining chromosome integrity and modulating chemosensitivity in response to
      irofulven-induced DNA damage. Therefore, this study suggests that it might be
      clinically significant to target irofulven therapy to cancers defective for
      proteins of the Fanconi anemia-BRCA pathway.

PMID- 17172420
TI  - Interleukin-13 receptor-targeted nanovesicles are a potential therapy for
      glioblastoma multiforme.
AB  - The difficulties associated with treatment of malignant brain tumors are well
      documented. For example, local infiltration of high-grade astrocytomas prevents
      the complete resection of all malignant cells. It is, therefore, critical to
      develop delivery systems for chemotherapeutic agents that ablate individual
      cancer cells without causing diffuse damage to surrounding brain tissue. Here, we
      describe sterically stable human interleukin-13 (IL-13)-conjugated liposomes,
      which efficiently bind to the brain cancer cells that overexpress the IL-13
      receptor alpha2 protein. The conjugated liposomes bind to glioblastoma multiforme
      tissue specimens but not to normal cortex. Conjugating the liposomes with human
      IL-13 allows for specific binding to glioma cells and uptake of the liposomes via
      endocytosis. Delivering doxorubicin to glioma cells by IL-13-conjugated liposomes
      results in enhanced cytotoxicity and increased accumulation and retention of drug
      in the glioma cells compared with delivery of free drug. The therapeutic
      potential and targeting efficacy of the IL-13-conjugated liposomes carrying
      doxorubicin was tested in vivo using a s.c. glioma tumor mouse model. Animals
      receiving i.p. injections of IL-13-conjugated liposomes carrying doxorubicin for
      7 weeks had a mean tumor volume of 37 mm3 compared with a mean volume of 192 mm3
      in animals injected with nontargeted liposomes. These results strongly suggest
      that IL-13-conjugated liposomes carrying cytotoxic agents are a feasible approach
      for creating a nanovesicle drug delivery system for brain tumor therapy.

PMID- 17172421
TI  - Chemosensitization of carcinoma cells using epithelial cell adhesion molecule
      targeted liposomal antisense against bcl-2/bcl-xL.
AB  - Nanoscale drug delivery systems, such as sterically stabilized immunoliposomes
      binding to internalizing tumor-associated antigens, can increase therapeutic
      efficacy and reduce toxicity to normal tissues compared with nontargeted
      liposomes. The epithelial cell adhesion molecule (EpCAM) is of interest as a
      ligand for targeted drug delivery because it is abundantly expressed in solid
      tumors but shows limited distribution in normal tissues. To generate EpCAM
      specific immunoliposomes for targeted cancer therapy, the humanized single-chain
      Fv antibody fragment 4D5MOCB was covalently linked to the exterior of coated
      cationic liposomes. As anticancer agent, we encapsulated the previously described
      antisense oligonucleotide 4625 specific for both bcl-2 and bcl-xL. The EpCAM
      targeted immunoliposomes (SIL25) showed specific binding to EpCAM-overexpressing
      tumor cells, with a 10- to 20-fold increase in binding compared with nontargeted
      control liposomes. No enhanced binding was observed on EpCAM-negative control
      cells. On cell binding, SIL25 was efficiently internalized by receptor-mediated
      endocytosis, ultimately leading to down-regulation of both bcl-2 and bcl-xL
      expression on both the mRNA and protein level, which resulted in enhanced tumor
      cell apoptosis. In combination experiments, the use of SIL25 led to a 2- to 5
      fold sensitization of EpCAM-positive tumor cells of diverse origin to death
      induction by doxorubicin. Our data show the promise of EpCAM-specific drug
      delivery systems, such as antisense-loaded immunoliposomes, for targeted cancer
      therapy.

PMID- 17172422
TI  - Bisphenol A facilitates bypass of androgen ablation therapy in prostate cancer.
AB  - Prostatic adenocarcinomas depend on androgen for growth and survival. First line
      treatment of disseminated disease exploits this dependence by specifically
      targeting androgen receptor function. Clinical evidence has shown that androgen
      receptor is reactivated in recurrent tumors despite the continuance of androgen
      deprivation therapy. Several factors have been shown to restore androgen receptor
      activity under these conditions, including somatic mutation of the androgen
      receptor ligand-binding domain. We have shown previously that select tumor
      derived mutants of the androgen receptor are receptive to activation by bisphenol
      A (BPA), an endocrine-disrupting compound that is leached from polycarbonate
      plastics and epoxy resins into the human food supply. Moreover, we have shown
      that BPA can promote cell cycle progression in cultured prostate cancer cells
      under conditions of androgen deprivation. Here, we challenged the effect of BPA
      on the therapeutic response in a xenograft model system of prostate cancer
      containing the endogenous BPA-responsive AR-T877A mutant protein. We show that
      after androgen deprivation, BPA enhanced both cellular proliferation rates and
      tumor growth. These effects were mediated, at least in part, through androgen
      receptor activity, as prostate-specific antigen levels rose with accelerated
      kinetics in BPA-exposed animals. Thus, at levels relevant to human exposure, BPA
      can modulate tumor cell growth and advance biochemical recurrence in tumors
      expressing the AR-T877A mutation.

PMID- 17172423
TI  - Influence of small interfering RNA corresponding to ets homologous factor on
      senescence-associated modulation of prostate carcinogenesis.
AB  - Senescence is thought to be an inherent tumor-suppressive mechanism. In the
      process of identifying senescence-associated genes, we found significant
      suppression of the ets homologous factor (EHF) in cancer cells in a state of DNA
      damage-induced senescence. In this study, we show that EHF provides substantial
      drug resistance in PC-3 prostate cancer cells by inhibiting senescence and cell
      cycle arrest. Knockdown of EHF by small interfering RNA inhibited cell
      proliferation and induced a premature cellular senescence characterized by
      hypophosphorylation of Rb and increased level of p27, with concomitant decreases
      of cyclin A, cdc2, and E2F1. Telomeric repeat amplification protocol analysis
      showed that transient EHF knockdown significantly decreased telomerase activity,
      whereas this activity was increased by overexpression of EHF. In vivo
      tumorigenesis analyses revealed that tumors derived from EHF knockdown cells were
      significantly smaller than those derived from control cells (P < 0.0001).
      Further, the preestablished tumors were reduced after the injection of small
      interfering RNA corresponding to EHF (P = 0.0122). Collectively, these
      observations indicate that aberrant expression of EHF and the subsequent
      disruption of p27-mediated senescence and telomerase activity is likely to
      contribute significantly to tumor progression, and furthermore that EHF might be
      a promising target for future cancer therapeutics.

PMID- 17172425
TI  - Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian
      target of rapamycin pathway in breast cancer cells.
AB  - This study is the first to investigate the anticancer effect of plumbagin in
      human breast cancer cells. Plumbagin exhibited cell proliferation inhibition by
      inducing cells to undergo G2-M arrest and autophagic cell death. Blockade of the
      cell cycle was associated with increased p21/WAF1 expression and Chk2 activation,
      and reduced amounts of cyclin B1, cyclin A, Cdc2, and Cdc25C. Plumbagin also
      reduced Cdc2 function by increasing the association of p21/WAF1/Cdc2 complex and
      the levels of inactivated phospho-Cdc2 and phospho-Cdc25C by Chk2 activation.
      Plumbagin triggered autophagic cell death but not predominantly apoptosis.
      Pretreatment of cells with autophagy inhibitor bafilomycin suppressed plumbagin
      mediated cell death. We also found that plumbagin inhibited survival signaling
      through the phosphatidylinositol 3-kinase/AKT signaling pathway by blocking the
      activation of AKT and downstream targets, including the mammalian target of
      rapamycin, forkhead transcription factors, and glycogen synthase kinase 3beta.
      Phosphorylation of both of mammalian target of rapamycin downstream targets, p70
      ribosomal protein S6 kinase and 4E-BP1, was also diminished. Overexpression of
      AKT by AKT cDNA transfection decreased plumbagin-mediated autophagic cell death,
      whereas reduction of AKT expression by small interfering RNA potentiated the
      effect of plumbagin, supporting the inhibition of AKT being beneficial to
      autophagy. Furthermore, suppression of AKT by plumbagin enhanced the activation
      of Chk2, resulting in increased inactive phosphorylation of Cdc25C and Cdc2.
      Further investigation revealed that plumbagin inhibition of cell growth was also
      evident in a nude mouse model. Taken together, these results imply a critical
      role for AKT inhibition in plumbagin-induced G2-M arrest and autophagy of human
      breast cancer cells.

PMID- 17172424
TI  - RNA interference-mediated simultaneous down-regulation of urokinase-type
      plasminogen activator receptor and cathepsin B induces caspase-8-mediated
      apoptosis in SNB19 human glioma cells.
AB  - The invasive character of gliomas depends on proteolytic cleavage of the
      surrounding extracellular matrix. Cathepsin B and urokinase-type plasminogen
      activator receptor (uPAR) together are known to be overexpressed in gliomas and,
      as such, are attractive targets for gene therapy. In the present study, we used
      plasmid constructs to induce the RNA interference (RNAi)-mediated down-regulation
      of uPAR and cathepsin B in SNB19 human glioma cells. We observed that the
      simultaneous down-regulation of uPAR and cathepsin B induces the up-regulation of
      proapoptotic genes and initiates a collapse in mitochondrial Deltapsi. Cathepsin
      B and uPAR down-regulated cells showed increases in the expression of activated
      caspase-8 and DFF40/caspase-activated DNase. Nuclear translocation of AIF and Fas
      ligand translocation to the cell membrane were also observed. Ki67 and X-linked
      inhibitor of apoptosis protein levels decreased, thereby indicating apoptosis.
      These results suggest the involvement of uPAR-cathepsin B complex on the cell
      surface and its role in maintaining the viability of SNB19 glioma cells. In
      conclusion, RNAi-mediated down-regulation of uPAR and cathepsin B initiates a
      partial extrinsic apoptotic cascade accompanied by the nuclear translocation of
      AIF. Our study shows the potential of RNAi-mediated down-regulation of uPAR and
      cathepsin B in developing new therapeutics for gliomas.

PMID- 17172426
TI  - Tautomycetin inhibits growth of colorectal cancer cells through p21cip/WAF1
      induction via the extracellular signal-regulated kinase pathway.
AB  - Tautomycetin is an antifungal antibiotic retaining potent immunosuppressive
      function. We have identified the roles of tautomycetin on cellular proliferation
      and transformation of colorectal cancer cells. The proliferation and anchorage
      independent growth of HCT-15, HT-29, and DLD-1 colorectal cancer cells were
      efficiently inhibited without induction of apoptosis by 150 nmol tautomycetin.
      These growth inhibitory effects were dependent on p21Cip/WAF induction via the
      extracellular signal-regulated kinase pathway, and the tautomycetin effects were
      abolished in HCT-116 colon cells and eight other types of cells that did not
      induce p21Cip/WAF by 150 nmol tautomycetin. The crucial role of p21Cip/WAF1 in
      the extracellular signal-regulated kinase pathway-dependent antiproliferative
      responses by tautomycetin was confirmed by using p21Cip/WAF1 gene-deleted HCT-116
      cells. The growth inhibitory effect of tautomycetin was acquired by regulation of
      Raf-1 activity through inhibition of protein phosphatase type 1 and protein
      phosphatase type 2A with high preference toward protein phosphatase type 1.
      Tautomycetin could be a potential drug for colorectal cancer.

PMID- 17172427
TI  - Assessment of celecoxib pharmacodynamics in pancreatic cancer.
AB  - Cyclooxygenase-2 (COX-2) inhibitors are being developed as chemopreventive and
      anticancer agents. This study aimed to determine the biological effect of the COX
      2 inhibitor celecoxib in pancreatic cancer as an early step to the further
      development of the agent in this disease. Eight patients scheduled for resection
      of an infiltrating adenocarcinoma of the pancreas were randomized to receive
      celecoxib at a dose of 400 mg twice daily or placebo for 5 to 15 days before the
      surgery. In addition, carcinomas from nine additional patients were xenografted
      in nude mice, expanded, and treated with vehicle or celecoxib for 28 days.
      Celecoxib markedly decreased the intra-tumor levels of prostaglandin E2 in
      patient carcinomas and in the heterotransplanted xenografts. However, this effect
      did not result in inhibition of cell proliferation or microvessel density (as
      assessed by Ki67 and CD31 staining). In addition, a panel of markers, including
      bcl-2, COX-1, COX-2, and VEGF, did not change with treatment in a significant
      manner. Furthermore, there was no evidence of antitumor effects in the
      xenografted carcinomas. In summary, celecoxib efficiently inhibited the synthesis
      of prostaglandin E2 both in pancreatic cancer surgical specimens and in
      xenografted carcinomas but did not exert evident antitumor, antiproliferative, or
      antiangiogenic effect as a single agent. The direct pancreatic cancer xenograft
      model proved to be a valuable tool for drug evaluation and biological studies and
      showed similar results to those observed in resected pancreatic cancer specimens.

PMID- 17172428
TI  - Therapeutic interactions between stathmin inhibition and chemotherapeutic agents
      in prostate cancer.
AB  - Limitations of prostate cancer therapy may be overcome by combinations of
      chemotherapeutic agents with gene therapy directed against specific proteins
      critical for disease progression. Stathmin is overexpressed in many types of
      human cancer, including prostate cancer. Stathmin is one of the key regulators of
      the microtubule network and the mitotic spindle and provides an attractive
      therapeutic target in cancer therapy. We recently showed that adenovirus-mediated
      gene transfer of anti-stathmin ribozyme could suppress the malignant phenotype of
      prostate cancer cells in vitro. In the current studies, we asked whether the
      therapeutic effects of stathmin inhibition could be further enhanced by exposure
      to different chemotherapeutic agents. Exposure of uninfected LNCaP human prostate
      cancer cells or cells infected with a control adenovirus to Taxol, etoposide, 5
      fluorouracil (5-FU), or Adriamycin resulted in modest decrease in proliferation
      and clonogenicity. Interestingly, exposure of cells infected with an anti
      stathmin adenovirus to Taxol or etoposide resulted in a complete loss of
      proliferation and clonogenicity, whereas exposure of the same cells to 5-FU or
      Adriamycin potentiated the growth-inhibitory effects of the anti-stathmin
      ribozyme, but the cells continued to proliferate. Terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling analysis of uninfected cells or cells
      infected with a control adenovirus showed modest induction of apoptosis in the
      presence of different drugs. In contrast, cells infected with the anti-stathmin
      adenovirus showed a marked increase in apoptosis on exposure to Taxol or
      etoposide and a modest increase on exposure to 5-FU or Adriamycin. Overall, the
      effects of combinations of anti-stathmin ribozyme with Taxol or etoposide were
      synergistic, whereas the effects of combinations of anti-stathmin ribozyme with 5
      FU or Adriamycin were additive. Moreover, triple combination of anti-stathmin
      ribozyme with low noninhibitory concentrations of Taxol and etoposide resulted in
      a profound synergistic inhibition of proliferation, clonogenicity, and marked
      induction of apoptosis. This synergy might be very relevant for the treatment of
      prostate cancer because Taxol and etoposide are two of the most effective agents
      in this disease. Thus, this combination may provide a novel form of prostate
      cancer therapy that would avoid toxicities associated with the use of multiple
      chemotherapeutic agents at full therapeutic doses.

PMID- 17172429
TI  - Preclinical pharmacokinetics, tissue distribution, and antitumor activity of a
      folate-hapten conjugate-targeted immunotherapy in hapten-immunized mice.
AB  - Folic acid (pteroylglutamic acid) represents a useful ligand for targeted cancer
      therapies because it binds to a common epithelial tumor antigen known as the
      folate receptor. We previously devised an immunotherapy strategy that uses a
      bispecific ligand, a folate-hapten (FITC) conjugate, to redirect endogenously
      induced anti-FITC antibodies to folate receptor-positive tumor cells following
      parenteral administration. Here, we present results from preclinical
      pharmacokinetic and tissue biodistribution studies using a radioactive folate
      FITC conjugate and results from dose optimization studies done in tumor-bearing
      animals. Folate-FITC was found to be rapidly eliminated in non-immunized mice;
      however, in immunized hosts, folate-FITC was shown to form immune complexes with
      FITC-specific antibodies, the consequence of which was a approximately 173-fold
      increase in drug exposure (i.e., area under the curve). Using a newly developed
      ELISA assay, the extent of circulating anti-FITC antibodies occupied by
      parenterally given folate-FITC was determined to be proportional to the given
      dose. Furthermore, high doses of folate-FITC were found to promote the
      cosaturation of tumor cell surface folate receptors and circulating FITC-specific
      antibodies, blocking the immune recognition of tumor cells and thereby reducing
      antitumor activity. Nonetheless, by extending the duration of treatment and
      administering subsaturating doses of folate-FITC, enhanced antitumor response was
      observed in mice bearing established folate receptor-positive M109 tumors.
      Overall, results from the present study may help to guide clinicians through on
      going clinical investigations of folate-targeted immunotherapy.

PMID- 17172430
TI  - Photodynamic therapy mediates the oxygen-independent activation of hypoxia
      inducible factor 1alpha.
AB  - Photodynamic therapy (PDT) induces the expression of the hypoxia-inducible factor
      1alpha (HIF-1alpha) subunit of the HIF-1 transcription factor and its target
      genes in vitro and in vivo. PDT also induces the expression of the enzyme
      cyclooxygenase-2 and its metabolite, prostaglandin E2 (PGE2). PGE2 and hypoxia
      act independently and synergistically to increase HIF-1alpha accumulation and
      nuclear translocation. To examine the expression of HIF-1 target genes in
      response to PDT-mediated oxidative stress and PGE2 under normoxic conditions, we
      established EMT6 cells transfected with a plasmid consisting of a hypoxia
      response element promoter and a downstream gene encoding for green fluorescent
      protein (GFP). To examine the temporal kinetics of HIF-1alpha nuclear
      translocation in response to PDT, we transfected a second line of EMT6 cells with
      a GFP-tagged HIF-1alpha fusion vector. Cell monolayers were incubated with 1
      microg mL(-1) Photofrin for 24 h and irradiated with fluences of 1, 2.5, and 5 J
      cm(-2). Direct measurement of oxygen concentration during irradiation confirmed
      that cells remained well oxygenated. Cells were also exposed to 1 and 10
      micromol/L PGE2 for 3 h. In normoxic conditions, Photofrin, PDT, and PGE2
      treatment activated HIF-1alpha and induced its nuclear translocation. Maximal
      Photofrin-PDT-mediated HIF-1alpha activation was intermediate in magnitude
      between that induced by PGE2 and that by the hypoxia mimic cobalt chloride. This
      work establishes that PDT induces significant activation of the HIF-1alpha
      pathway in the absence of hypoxia and supports the interpretation that the
      induction of HIF-1 target genes by PDT may be mediated, at least in part, by the
      prostaglandin pathway.

PMID- 17172431
TI  - Apoptosis induced by selenomethionine and methioninase is superoxide mediated and
      p53 dependent in human prostate cancer cells.
AB  - Selenomethionine (SeMet) is the chemical form or major component of selenium used
      for cancer chemoprevention in several clinical trials. However, evidence from
      experimental studies indicates that SeMet has weaker anticancer effects than most
      other forms of selenium. Recent studies showed that the anticancer activity of
      SeMet can be enhanced by methioninase (METase), indicating that SeMet metabolites
      are responsible for its anticancer activity. In the present study, we showed that
      wild-type p53-expressing LNCaP human prostate cancer cells were more sensitive to
      cotreatment with SeMet and METase than p53-null PC3 human prostate cancer cells.
      SeMet and METase cotreatment significantly increased levels of superoxide and
      apoptosis in LNCaP cells. Cotreatment with SeMet and METase resulted in increased
      levels of phosphorylated p53 (Ser15), total p53, Bax, and p21(Waf1) proteins.
      LNCaP cells treated with SeMet and METase also showed p53 translocation to
      mitochondria, decreased mitochondrial membrane potential, cytochrome c release
      into the cytosol, and activation of caspase-9. The effects of SeMet and METase
      were suppressed by pretreatment with a synthetic superoxide dismutase mimic or by
      knockdown of p53 via RNA interference. Reexpression of wild-type p53 in PC3 cells
      resulted in increases in superoxide production, apoptosis, and caspase-9 activity
      and a decrease in mitochondrial membrane potential following cotreatment with
      SeMet and METase. Our study shows that apoptosis induced by SeMet plus METase is
      superoxide mediated and p53 dependent via mitochondrial pathway(s). These results
      suggest that superoxide and p53 may play a role in cancer chemoprevention by
      selenium.

PMID- 17172432
TI  - Methyl-3-indolylacetate inhibits cancer cell invasion by targeting the MEK1/2
      ERK1/2 signaling pathway.
AB  - Epidemiologic studies have suggested an inverse correlation between dietary
      intake of cruciferous vegetables and cancer risk. It is thus of interest to
      investigate the anticancer potential of phytochemicals presented in cruciferous
      vegetables. In this study, methyl-3-indolylacetate (MIA), a cruciferous indole
      for which the bioactivity has not been previously reported, was found to
      significantly suppress the invasion of cancer cells stimulated by the 12-O
      tetradecanoyl-phorbol-13-acetate (TPA). Our data show that MIA pretreatments
      inhibited matrix metalloproteinase 9 (MMP-9) expression in a concentration
      dependent manner, resulting in decreased MMP-9 activity. By using real-time
      reverse transcription-PCR, luciferase reporter gene assay, and electrophoretic
      mobility shift assay, we provided convincing evidence that MIA suppresses MMP-9
      gene transcription via targeting the activator protein-1 signaling but not the
      nuclear factor-kappaB pathway. The TPA-induced mitogen-activated protein kinase
      (MAPK) activation cascade was also analyzed. Despite extensive activation of
      major MAPKs [c-Jun NH2-terminal kinase, p38, and extracellular signal-regulated
      kinase-1/2 (ERK1/2)] under TPA stimulation, only the ERK1/2 activation and its
      consequent nuclear translocation were found to be diminished by MIA.
      Interestingly, MIA did not affect the TPA-induced phosphorylation of either c-Raf
      or MAPK/ERK kinase-1/2 (MEK1/2), two upstream kinases of ERK. Moreover, using the
      in vitro kinase assay, MIA was shown to inhibit the kinase activity of MEK1/2,
      the upstream kinases of ERK, suggesting that MEK is the major molecular target of
      MIA. In conclusion, data from this study provided new insight into the anticancer
      potential of MIA, a cruciferous vegetable-derived indole compound.

PMID- 17172433
TI  - Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM
      Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human
      prostate carcinoma DU145 cells.
AB  - We recently reported that gallic acid is a major active agent responsible for
      grape seed extract activity in DU145 human prostate carcinoma cells. The present
      study was conducted to examine its efficacy and associated mechanism. Gallic acid
      treatment of DU145 cells resulted in a strong cell growth inhibition, cell cycle
      arrest, and apoptotic death in a dose- and time-dependent manner, together with a
      decrease in cyclin-dependent kinases and cyclins but strong induction in
      Cip1/p21. Additional mechanistic studies showed that gallic acid induces an early
      Tyr(15) phosphorylation of cell division cycle 2 (cdc2). Further upstream, gallic
      acid also induced phosphorylation of both cdc25A and cdc25C via ataxia
      telangiectasia mutated (ATM)-checkpoint kinase 2 (Chk2) activation as a DNA
      damage response evidenced by increased phospho-histone 2AX (H2A.X) that is
      phosphorylated by ATM in response to DNA damage. Time kinetics of ATM
      phosphorylation, together with those of H2A.X and Chk2, was in accordance with an
      inactivating phosphorylation of cdc25A and cdc25C phosphatases and cdc2 kinase,
      suggesting that gallic acid increases cdc25A/C-cdc2 phosphorylation and thereby
      inactivation via ATM-Chk2 pathway following DNA damage that induces cell cycle
      arrest. Caffeine, an ATM/ataxia telangiectasia-rad3-related inhibitor, reversed
      gallic acid-caused ATM and H2A.X phosphorylation and cell cycle arrest,
      supporting the role of ATM pathway in gallic acid-induced cell cycle arrest.
      Additionally, gallic acid caused caspase-9, caspase-3, and poly(ADP)ribose
      polymerase cleavage, but pan-caspase inhibitor did not reverse apoptosis,
      suggesting an additional caspase-independent apoptotic mechanism. Together, this
      is the first report identifying gallic acid efficacy and associated mechanisms in
      an advanced and androgen-independent human prostate carcinoma DU145 cells,
      suggesting future in vivo efficacy studies with this agent in preclinical
      prostate cancer models.

PMID- 17172434
TI  - Effects of the chemotherapeutic agent doxorubicin on the protein C anticoagulant
      pathway.
AB  - Although chemotherapy treatment is associated with an increased risk of
      thrombosis, the pathogenic mechanisms for the thrombogenic effect of
      chemotherapeutic drugs are poorly understood. We hypothesize that exposure of
      vascular endothelial cells to chemotherapeutic agents results in the loss of a
      thromboresistant phenotype. In this study, we examined the effects of the
      chemotherapeutic agent doxorubicin on the endothelium-based protein C
      anticoagulant pathway. The endothelial cell protein C receptor (EPCR) and
      thrombomodulin are two endothelial cell surface receptors required for the
      conversion of zymogen protein C to the anticoagulant enzyme activated protein C.
      Exposure of human umbilical vein endothelial cells (HUVEC) to doxorubicin
      resulted in a dose- and time-dependent decrease in cell surface EPCR levels. This
      decrease occurred as a result of receptor shedding as well as from a down
      regulation in EPCR mRNA levels. In contrast, doxorubicin treatment of HUVECs
      resulted in a dose- and time-dependent increase in cell surface thrombomodulin
      attributed to an up-regulation of thrombomodulin mRNA levels. The net effect of
      the doxorubicin-induced changes in EPCR and thrombomodulin levels was a decrease
      in the capacity of HUVECs to convert protein C to activated protein C.
      Preliminary studies suggest that doxorubicin free radical metabolites mediate the
      doxorubicin-induced changes in EPCR expression but not those of thrombomodulin
      expression. In summary, these results suggest that doxorubicin alters the
      hemostatic balance of endothelial cells by down-regulating the endothelium-based
      protein C anticoagulant pathway.

PMID- 17172435
TI  - Analysis of Thalassiosira pseudonana silicon transporters indicates distinct
      regulatory levels and transport activity through the cell cycle.
AB  - An analysis of the expression and activity of silicon transporters (SITs) was
      done on synchronously growing cultures of the diatom Thalassiosira pseudonana to
      provide insight into the role these proteins play in cellular silicon metabolism
      during the cell cycle. The first SIT-specific polyclonal peptide antibody was
      generated and used in the immunoblot analysis of whole-cell protein lysates to
      monitor SIT protein levels during synchronized progression through the cell
      cycle. Peaks in SIT protein levels correlated with active periods of silica
      incorporation into cell wall substructures. Quantitative real-time PCR on each of
      the three distinct SIT genes (TpSIT1, TpSIT2, and TpSIT3) showed that mRNA levels
      for the most highly expressed SIT genes peaked during the S phase of the cell
      cycle, a period prior to maximal silicon uptake and during which cell wall
      silicification does not occur. Variations in protein and mRNA levels did not
      correlate, suggesting that a significant regulatory step of SITs is at the
      translational or posttranslational level. Surge uptake rates also did not
      correlate with SIT protein levels, suggesting that SIT activity is internally
      controlled by the rate of silica incorporation. This is the first study to
      characterize SIT mRNA and protein expression and cellular uptake kinetics during
      the course of the cell cycle and cell wall synthesis, and it provides novel
      insight into SIT regulation.

PMID- 17172436
TI  - Mpt5p, a stress tolerance- and lifespan-promoting PUF protein in Saccharomyces
      cerevisiae, acts upstream of the cell wall integrity pathway.
AB  - Pumilio family (PUF) proteins affect specific genes by binding to, and inhibiting
      the translation or stability of, their transcripts. The PUF domain is required
      and sufficient for this function. One Saccharomyces cerevisiae PUF protein, Mpt5p
      (also called Puf5p or Uth4p), promotes stress tolerance and replicative life span
      (the maximum number of doublings a mother cell can undergo before entering into
      senescence) by an unknown mechanism thought to partly overlap with, but to be
      independent of, the cell wall integrity (CWI) pathway. Here, we found that
      mpt5Delta mutants also display a short chronological life span (the time cells
      stay alive in saturated cultures in synthetic medium), a defect that is
      suppressed by activation of CWI signaling. We found that Mpt5p is an upstream
      activator of the CWI pathway: mpt5Delta mutants display the appropriate
      phenotypes and genetic interactions, display low basal activity of the pathway,
      and are defective in activation of the pathway upon thermal stress. A set of
      mRNAs that specifically bind to Mpt5p was recently reported. One such putative
      target, LRG1, encodes a GTPase-activating protein for Rho1p that directly links
      Mpt5p to CWI signaling: Lrg1p inhibits CWI signaling, LRG1 mRNA contains a
      consensus Mpt5p-binding site in its putative 3' untranslated region, loss of
      Lrg1p suppresses the temperature sensitivity and CWI signaling defects of
      mpt5Delta mutants, and LRG1 mRNA abundance is inhibited by Mpt5p. We conclude
      that Mpt5p is required for normal replicative and chronological life spans and
      that the CWI pathway is a key and direct downstream target of this PUF protein.

PMID- 17172437
TI  - Temporal and spatial control of HGC1 expression results in Hgc1 localization to
      the apical cells of hyphae in Candida albicans.
AB  - The human fungal pathogen Candida albicans can undergo a morphological transition
      from a unicellular yeast growth form to a multicellular hyphal growth form.
      During hyphal growth, cell division is asymmetric. Only the apical cell divides,
      whereas subapical cells remain in G(1), and cell surface growth is highly
      restricted to the tip of the apical cell. Hgc1, a hypha-specific, G(1) cyclin
      like protein, is essential for hyphal development. Here, we report, using
      indirect immunofluorescence, that Hgc1 is preferentially localized to the
      dividing apical cells of hyphae. Hgc1 protein is rapidly degraded in a cell cycle
      independent manner, and the protein turnover likely occurs in both the apical and
      the subapical cells of hyphae. In addition to rapid protein turnover, the HGC1
      transcript is also dynamically regulated during cell cycle progression in hyphal
      growth. It is induced upon germ tube formation in early G(1); the transcript
      level is reduced during the G(1)/S transition and peaks again around the G(2)/M
      phase in the subsequent cell cycles. Transcription from the HGC1 promoter is
      essential for its apical cell localization, as Hgc1 no longer exhibits
      preferential apical localization when expressed under the MAL2 promoter. Using
      fluorescence in situ hybridization, the HGC1 transcript is detected only in the
      apical cells of hyphae, suggesting that HGC1 is transcribed in the apical cell.
      Therefore, the preferential localization of Hgc1 to the apical cells of hyphae
      results from the dynamic temporal and spatial control of HGC1 expression.

PMID- 17172438
TI  - Site-directed alkylation and the alternating access model for LacY.
AB  - In a functional lactose permease mutant from Escherichia coli (LacY) devoid of
      native Cys residues, almost every residue was replaced individually with Cys and
      tested for reactivity with the permeant alkylating agent N-ethylmaleimide in
      right-side-out membrane vesicles. Here we present the results in the context of
      the crystal structure of LacY. Engineered Cys replacements located near or within
      the inward-facing hydrophilic cavity or at other solvent-accessible positions in
      LacY react well with this alkylating agent. Cys residues facing the low
      dielectric of the membrane or located in tightly packed regions of the structure
      react poorly. Remarkably, in the presence of ligand, increased reactivity is
      observed with Cys replacements located predominantly on the periplasmic side of
      the sugar-binding site. In contrast, other Cys replacements largely on the
      cytoplasmic side of the binding site exhibit decreased reactivity. Furthermore,
      both sets of Cys replacements in the putative cavities are located at the
      periplasmic (increased reactivity) and cytoplasmic (decreased reactivity) ends of
      the same helices and distributed in a pseudosymmetrical manner. The results are
      consistent with a model in which the single sugar-binding site in the approximate
      middle of the molecule is alternately exposed to either side of the membrane due
      to opening and closing of cytoplasmic and periplasmic hydrophilic cavities.

PMID- 17172439
TI  - Structural transitions of complement component C3 and its activation products.
AB  - Complement sensitizes pathogens for phagocytosis and lysis. We use electron
      microscopy to examine the structural transitions in the activation of the pivotal
      protein in the complement pathway, C3. In the cleavage product C3b, the position
      of the thioester domain moves approximately 100 Angstrom, which becomes
      covalently coupled to antigenic surfaces. In the iC3b fragment, cleavage in an
      intervening domain creates a long flexible linker between the thioester domain
      and the macroglobulin domain ring of C3. Studies on two products of nucleophile
      addition to C3 reveal a structural intermediate in activation, and a final
      product, in which the anaphylatoxin domain has undergone a remarkable movement
      through the macroglobulin ring.

PMID- 17172440
TI  - Order from disorder: Self-organization in mammalian hair patterning.
AB  - Hairs, feathers, and scales normally exhibit precise orientations with respect to
      the body axes. In Frizzled6 (Fz6)(-/-) mice, the global orientation of hair
      follicles is disrupted, leading to waves, whorls, and tufts, each comprising many
      hundreds of hairs. By analyzing the orientation of developing hair follicles, we
      observed that the nearly parallel arrangement of wild-type (WT) hairs arises from
      fields of imperfectly aligned follicles, and that the Fz6(-/-) hair patterns
      arise from fields of grossly misoriented or randomly oriented follicles. Despite
      their large size, both mutant and WT hair follicles display a remarkable and
      unexpected plasticity, reorienting on a time scale of days in what seems to be a
      self-organized refinement process. The essential features of this process can be
      studied with a simple cellular automata model in which a local consensus "rule"
      acts iteratively to bias each hair's orientation in favor of the average
      orientation of its neighbors. These experiments define two systems for hair
      orientation: a global orienting system that acts early in development and is Fz6
      dependent, and a local self-organizing system that acts later and is Fz6
      independent.

PMID- 17172442
TI  - Adhesion and detachment mechanisms of sugar surfaces from the solid (glassy) to
      liquid (viscous) states.
AB  - The viscosity of some sugars varies continuously by approximately 10 orders of
      magnitude over a temperature range of 50 degrees C. Sugars are therefore ideal
      model materials for studying the failure mechanism of materials as they change
      from the solid to the liquid state. We have used a surface forces apparatus
      coupled to interference and optical microscopy imaging to study the way two sugar
      surfaces adhere and detach from adhesive contact. The sugar-coated layers on mica
      displayed significant loading-unloading hysteresis, and the adhesive strength and
      failure mechanism during a "loading-unloading cycle" depended on the loading
      rate, contact time, and unloading rate. The failure of two glassy sugar surfaces
      was manifested by the nucleation of many sharp microcracks at the external
      boundary that rapidly propagate along the original contact interface. At the
      other extreme, when the material is a liquid, "failure" occurs through the
      nucleation and inward growth of large rounded ripples, characteristic of a
      Saffman-Taylor fingering instability. In the transition from glassy to viscous
      failure, sharp crack tips and smooth rounded fingers coexist during the crack
      propagation. In addition, whereas the detachment geometry of two glassy surfaces
      was characterized by a peeling-like mechanism along a plane, the fingers
      associated with the "snapping" of a liquid neck extended in all directions. These
      findings provide insights into the adhesion and failure mechanisms of materials
      at the micro/nanoscales and are also relevant to the action of interparticle
      forces between sugar particles, such as those used in inhalation drug delivery.

PMID- 17172441
TI  - Filamin A (FLNA) is required for cell-cell contact in vascular development and
      cardiac morphogenesis.
AB  - Mutations in the human Filamin A (FLNA) gene disrupt neuronal migration to the
      cerebral cortex and cause cardiovascular defects. Complete loss of Flna in mice
      results in embryonic lethality with severe cardiac structural defects involving
      ventricles, atria, and outflow tracts, as well as widespread aberrant vascular
      patterning. Despite these widespread developmental defects, migration and
      motility of many cell types does not appear to be affected. Instead, Flna-null
      embryos display abnormal epithelial and endothelial organization and aberrant
      adherens junctions in developing blood vessels, heart, brain, and other tissues.
      Essential roles for FLNA in intercellular junctions provide a mechanism for the
      diverse developmental defects seen in patients with FLNA mutations.

PMID- 17172443
TI  - Modulation of Leydig cell function by cyclic nucleotide phosphodiesterase 8A.
AB  - Leydig cells produce testosterone in the testes under the pulsatile control of
      pituitary luteinizing hormone (LH). cAMP is the intracellular messenger for LH
      action on steroidogenesis, and pharmacological evidence indicates that the
      response to LH can be modulated by cyclic nucleotide phosphodiesterases (PDEs).
      However the types and roles of the PDEs present in Leydig cells have not been
      fully defined. We report here that PDE8A is expressed in Leydig cells, and using
      PDE8A knockout mice we provide evidence that PDE8A is a key regulator of LH
      signaling and steroidogenesis. A 4-fold increase in the sensitivity to LH for
      testosterone production was detected in Leydig cells isolated from PDE8A knockout
      mice. In Leydig cells from wild-type mice, 3-isobutyl-1-methylxanthine, a
      compound that inhibits all cAMP PDEs except PDE8A, elicited only a small increase
      in the sensitivity of testosterone production to LH. However, in the PDE8-null
      mice, the effect of this inhibitor is much more pronounced. These observations
      indicate that PDE8A and at least one other PDE control the same or a
      complementary pool of cAMP that mediates LH-regulated steroidogenesis. Overall,
      these results suggest that pharmacological manipulation of PDE8A, alone or in
      combination with other PDEs present in Leydig cells, may be exploited to modulate
      testosterone synthesis and possibly to treat various conditions where the local
      levels of this androgen need to be altered.

PMID- 17172444
TI  - Bidirectional signaling between calcium channels of skeletal muscle requires
      multiple direct and indirect interactions.
AB  - We have defined regions of the skeletal muscle ryanodine receptor (RyR1)
      essential for bidirectional signaling with dihydropyridine receptors (DHPRs) and
      for the organization of DHPR into tetrad arrays by expressing RyR1-RyR3 chimerae
      in dyspedic myotubes. RyR1-RyR3 constructs bearing RyR1 residues 1-1681 restored
      wild-type DHPR tetrad arrays and, in part, skeletal-type excitation-contraction
      (EC) coupling (orthograde signaling) but failed to enhance DHPR Ca(2+) currents
      (retrograde signaling) to WT RyR1 levels. Within this region, the D2 domain
      (amino acids 1272-1455), although ineffective on its own, dramatically enhanced
      the formation of tetrads and EC coupling rescue by constructs that otherwise are
      only partially effective. These findings suggest that the orthograde signal and
      DHPR tetrad formation require the contributions of numerous RyR regions.
      Surprisingly, we found that RyR3, although incapable of supporting EC coupling or
      tetrad formation, restored a significant level of Ca(2+) current, revealing a
      functional interaction with the skeletal muscle DHPR. Thus, our data support the
      hypotheses that (i) the structural/functional link between RyR1 and the skeletal
      muscle DHPR requires multiple interacting regions, (ii) the D2 domain of RyR1
      plays a key role in stabilizing this interaction, and (iii) a form of retrograde
      signaling from RyR3 to the DHPR occurs in the absence of direct protein-protein
      interactions.

PMID- 17172445
TI  - Identification of long-range regulatory elements in the protocadherin-alpha gene
      cluster.
AB  - The clustered protocadherins (Pcdh) are encoded by three closely linked gene
      clusters (Pcdh-alpha, -beta, and -gamma) that span nearly 1 million base pairs of
      DNA. The Pcdh-alpha gene cluster encodes a family of 14 distinct cadherin-like
      cell surface proteins that are expressed in neurons and are present at synaptic
      junctions. Individual Pcdh-alpha mRNAs are assembled from one of 14 "variable"
      (V) exons and three "constant" exons in a process that involves both differential
      promoter activation and alternative pre-mRNA splicing. In individual neurons,
      only one (and rarely two) of the Pcdh alpha1-12 promoters is independently and
      randomly activated on each chromosome. Thus, in most cells, this unusual form of
      monoallelic expression leads to the expression of two different Pcdh-alpha 1-12 V
      exons, one from each chromosome. The two remaining V exons in the cluster (Pcdh
      alphaC1 and alphaC2) are expressed biallelically in every neuron. The mechanisms
      that underlie promoter choice and monoallelic expression in the Pcdh-alpha gene
      cluster are not understood. Here we report the identification of two long-range
      cis-regulatory elements in the Pcdh-alpha gene cluster, HS5-1 and HS7. We show
      that HS5-1 is required for maximal levels of expression from the Pcdh alpha1-12
      and alphaC1 promoters, but not the Pcdh-alphaC2 promoter. The nearly cluster-wide
      requirement of the HS5-1 element is consistent with the possibility that the
      monoallelic expression of Pcdh-alpha V exons is a consequence of competition
      between individual V exon promoters for the two regulatory elements.

PMID- 17172446
TI  - The first armadillo repeat is involved in the recognition and regulation of beta
      catenin phosphorylation by protein kinase CK1.
AB  - Multiple phosphorylation of beta-catenin by glycogen synthase kinase 3 (GSK3) in
      the Wnt pathway is primed by CK1 through phosphorylation of Ser-45, which lacks a
      typical CK1 canonical sequence. Synthetic peptides encompassing amino acids 38-64
      of beta-catenin are phosphorylated by CK1 on Ser-45 with low affinity (K(m)
      approximately 1 mM), whereas intact beta-catenin is phosphorylated at Ser-45 with
      very high affinity (K(m) approximately 200 nM). Peptides extended to include a
      putative CK1 docking motif (FXXXF) at 70-74 positions or a F74AA mutation in full
      length beta-catenin had no significant effect on CK1 phosphorylation efficiency.
      beta-Catenin C-terminal deletion mutants up to residue 181 maintained their high
      affinity, whereas removal of the 131-181 fragment, corresponding to the first
      armadillo repeat, was deleterious, resulting in a 50-fold increase in K(m) value.
      Implication of the first armadillo repeat in beta-catenin targeting by CK1 is
      supported in that the Y142E mutation, which mimics phosphorylation of Tyr-142 by
      tyrosine kinases and promotes dissociation of beta-catenin from alpha-catenin,
      further improves CK1 phosphorylation efficiency, lowering the K(m) value to <50
      nM, approximating the physiological concentration of beta-catenin. In contrast,
      alpha-catenin, which interacts with the N-terminal region of beta-catenin,
      prevents Ser-45 phosphorylation of CK1 in a dose-dependent manner. Our data show
      that the integrity of the N-terminal region and the first armadillo repeat are
      necessary and sufficient for high-affinity phosphorylation by CK1 of Ser-45. They
      also suggest that beta-catenin association with alpha-catenin and beta-catenin
      phosphorylation by CK1 at Ser-45 are mutually exclusive.

PMID- 17172447
TI  - S-adenosylhomocysteine hydrolase is localized at the front of chemotaxing cells,
      suggesting a role for transmethylation during migration.
AB  - Chemotaxis of bacteria requires regulated methylation of chemoreceptors. However,
      despite considerable effort in the 1980s, transmethylation has never been
      established as a component of eukaryotic cell chemotaxis. S-adenosylhomocysteine
      (SAH), the product formed when the methyl group of the universal donor S
      adenosylmethionine (SAM) is transferred to an acceptor molecule, is a potent
      inhibitor of all transmethylation reactions. In eukaryotic cells, this inhibition
      is relieved by hydrolysis of SAH to adenosine and homocysteine catalyzed by SAH
      hydrolase (SAHH). We now report that SAHH, which is diffuse in the cytoplasm of
      nonmotile Dictyostelium amoebae and human neutrophils, concentrates with F-actin
      in pseudopods at the front of motile, chemotaxing cells, but is not present in
      filopodia or at the very leading edge. Tubercidin, an inhibitor of SAHH, inhibits
      both chemotaxis and chemotaxis-dependent cell streaming of Dictyostelium, and
      chemotaxis of neutrophils at concentrations that have little effect on cell
      viability. Tubercidin does not inhibit starvation-induced expression of the cAMP
      receptor, cAR1, or G protein-mediated stimulation of adenylyl cyclase activity
      and actin polymerization in Dictyostelium. Tubercidin has no effect on either
      capping of Con A receptors or phagocytosis in Dictyostelium. These results add
      SAHH to the list of proteins that redistribute in response to chemotactic signals
      in Dictyostelium and neutrophils and strongly suggest a role for transmethylation
      in chemotaxis of eukaryotic cells.

PMID- 17172448
TI  - Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter.
AB  - Discs-large homolog 1 (DLGH1) is a mouse ortholog of the Drosophila discs-large
      (DLG) tumor suppressor protein, a founding member of the PDZ and MAGUK protein
      families. DLG proteins play important roles in regulating cell proliferation,
      epithelial cell polarity, and synapse formation and function. Here, we generated
      a null allele of Dlgh1 and studied its role in urogenital development. Dlgh1(-/-)
      mice developed severe urinary tract abnormalities, including congenital
      hydronephrosis, which is the leading cause of renal failure in infants and
      children. DLGH1 is expressed in the developing ureter; in its absence, the
      stromal cells that normally lie between the urothelial and smooth muscle layers
      were missing. Moreover, in ureteric smooth muscle, the circular smooth muscle
      cells were misaligned in a longitudinal orientation. These abnormalities in the
      ureter led to severely impaired ureteric peristalsis. Similar smooth muscle
      defects are observed frequently in patients with ureteropelvic junction
      obstruction, a common form of hydronephrosis. Our results suggest that (i)
      besides its well documented role in regulating epithelial polarity, Dlgh1 also
      regulates smooth muscle orientation, and (ii) human DLG1 mutations may contribute
      to hereditary forms of hydronephrosis.

PMID- 17172449
TI  - Phosphoinositide 3-kinase gamma/delta inhibition limits infarct size after
      myocardial ischemia/reperfusion injury.
AB  - Although phosphoinositide 3-kinases (PI3Ks) play beneficial pro-cell survival
      roles during tissue ischemia, some isoforms (gamma and delta) paradoxically
      contribute to the inflammation that damages these same tissues upon reperfusion.
      We therefore considered the possibility that selectively inhibiting
      proinflammatory PI3K isoforms during the reperfusion phase could ultimately limit
      overall tissue damage seen in ischemia/reperfusion injuries such as myocardial
      infarction. Panreactive and isoform-restricted PI3K inhibitors were identified by
      screening a novel chemical family; molecular modeling studies attributed isoform
      specificity based on rotational freedom of substituent groups. One compound
      (TG100-115) identified as a selective PI3K gamma/delta inhibitor potently
      inhibited edema and inflammation in response to multiple mediators known to
      participate in myocardial infarction, including vascular endothelial growth
      factor and platelet-activating factor; by contrast, endothelial cell mitogenesis,
      a repair process important to tissue survival after ischemic damage, was not
      disrupted. In rigorous animal MI models, TG100-115 provided potent
      cardioprotection, reducing infarct development and preserving myocardial
      function. Importantly, this was achieved when dosing well after myocardial
      reperfusion (up to 3 h after), the same time period when patients are most
      accessible for therapeutic intervention. In conclusion, by targeting pathologic
      events occurring relatively late in myocardial damage, we have identified a
      potential means of addressing an elusive clinical goal: meaningful
      cardioprotection in the postreperfusion time period.

PMID- 17172450
TI  - Selection for Staphylococcus aureus small-colony variants due to growth in the
      presence of Pseudomonas aeruginosa.
AB  - Opportunistic infections are often polymicrobial. Two of the most important
      bacterial opportunistic pathogens of humans, Pseudomonas aeruginosa and
      Staphylococcus aureus, frequently are coisolated from infections of catheters,
      endotracheal tubes, skin, eyes, and the respiratory tract, including the airways
      of people with cystic fibrosis (CF). Here, we show that suppression of S. aureus
      respiration by a P. aeruginosa exoproduct, 4-hydroxy-2-heptylquinoline-N-oxide
      (HQNO), protects S. aureus during coculture from killing by commonly used
      aminoglycoside antibiotics such as tobramycin. Furthermore, prolonged growth of
      S. aureus with either P. aeruginosa or with physiological concentrations of pure
      HQNO selects for typical S. aureus small-colony variants (SCVs), well known for
      stable aminoglycoside resistance and persistence in chronic infections, including
      those found in CF. We detected HQNO in the sputum of CF patients infected with P.
      aeruginosa, but not in uninfected patients, suggesting that this HQNO-mediated
      interspecies interaction occurs in CF airways. Thus, in all coinfections with P.
      aeruginosa, S. aureus may be underappreciated as a pathogen because of the
      formation of antibiotic-resistant and difficult to detect small-colony variants.
      Interspecies microbial interactions, analogous to those mediated by HQNO,
      commonly may alter not only the course of disease and the response to therapy,
      but also the population structure of bacterial communities that promote the
      health of host animals, plants, and ecosystems.

PMID- 17172451
TI  - Filamentation by Escherichia coli subverts innate defenses during urinary tract
      infection.
AB  - To establish disease, an infecting organism must overcome a vast array of host
      defenses. During cystitis, uropathogenic Escherichia coli (UPEC) subvert innate
      defenses by invading superficial umbrella cells and rapidly increasing in numbers
      to form intracellular bacterial communities (IBCs). In the late stages of the IBC
      pathway, filamentous and bacillary UPEC detach from the biofilm-like IBC, fluxing
      out of this safe haven to colonize the surrounding epithelium and initiate
      subsequent generations of IBCs, and eventually they establish a quiescent
      intracellular reservoir. Filamentous UPEC are not observed during acute infection
      in mice lacking functional Toll-like receptor 4 (TLR4), suggesting that the
      filamentous phenotype arises in response to host innate immunity. We investigated
      SulA, a cell division inhibitor associated with the SOS response, to gain insight
      into the role of filamentous UPEC in pathogenesis. A transcriptional reporter
      from P(sulA) revealed spatial and temporal differences in expression within IBCs,
      and it was active in the majority of filamentous UPEC. Although UTI89 and UTI89
      DeltasulA both formed first-generation IBCs equally well, UTI89 DeltasulA was
      sharply attenuated in formation of second-generation IBCs and establishment of
      the quiescent intracellular reservoir. The virulence of UTI89 DeltasulA was
      restored in TLR4-deficient mice, suggesting that filamentation facilitates the
      transition to additional rounds of IBC formation by subverting innate immune
      responses. These findings demonstrate that transient SulA-mediated inhibition of
      cell division is essential for UPEC virulence in the murine model of cystitis.

PMID- 17172452
TI  - Localized proton microcircuits at the biological membrane-water interface.
AB  - Cellular processes such as nerve conduction, energy metabolism, and import of
      nutrients into cells all depend on transport of ions across biological membranes
      through specialized membrane-spanning proteins. Understanding these processes at
      a molecular level requires mechanistic insights into the interaction between
      these proteins and the membrane itself. To explore the role of the membrane in
      ion translocation we used an approach based on fluorescence correlation
      spectroscopy. Specifically, we investigated exchange of protons between the water
      phase and the membrane surface, as well as diffusion of protons along membrane
      surfaces, at a single-molecule level. We show that the lipid head groups
      collectively act as a proton-collecting antenna, dramatically accelerating proton
      uptake from water to a membrane-anchored proton acceptor. Furthermore, the
      results show that proton transfer along the surface can be significantly faster
      than that between the lipid head groups and the surrounding water phase. Thus,
      ion translocation across membranes and between the different membrane protein
      components is a complex interplay between the proteins and the membrane itself,
      where the membrane acts as a proton-conducting link between membrane-spanning
      proton transporters.

PMID- 17172453
TI  - Processive enzyme mimic: Kinetics and thermodynamics of the threading and sliding
      process.
AB  - The kinetics and thermodynamics of the threading and dethreading process of
      polymers through the cavity of a synthetic toroidal host is investigated by
      studying its complexation with a series of end-functionalized polymers of
      different lengths containing an end group that is selectively recognized by the
      host. The system is designed in such a way that complexation is only observed if
      the host has traveled all of the way across the complete polymer. Detailed
      kinetic investigations using fluorescence spectroscopy have revealed that the
      barrier for this process is length dependent and most likely related to the
      stretching of the polymer. Moreover, the results indicate that our previously
      reported processive enzyme mimic most likely operates by randomly sliding along
      its macromolecular substrate.

PMID- 17172454
TI  - Topological dynamics of holins in programmed bacterial lysis.
AB  - The fate of phage-infected bacteria is determined by the holin, a small membrane
      protein that triggers to disrupt the membrane at a programmed time, allowing a
      lysozyme to attack the cell wall. S(21)68, the holin of phage 21, has two
      transmembrane domains (TMDs) with a predicted N-in, C-in topology. Surprisingly,
      TMD1 of S(21)68 was found to be dispensable for function, to behave as a SAR
      ("signal-anchor-release") domain in exiting the membrane to the periplasm, and to
      engage in homotypic interactions in the soluble phase. The departure of TMD1 from
      the bilayer coincides with the lethal triggering of the holin and is accelerated
      by membrane depolarization. Basic residues added at the N terminus of S(21)68
      prevent the escape of TMD1 to the periplasm and block hole formation by TMD2.
      Lysis thus depends on dynamic topology, in that removal of the inhibitory TMD1
      from the bilayer frees TMD2 for programmed formation of lethal membrane lesions.

PMID- 17172455
TI  - Rae1 interaction with NuMA is required for bipolar spindle formation.
AB  - In eukaryotic cells, the faithful segregation of daughter chromosomes during cell
      division depends on formation of a microtubule (MT)-based bipolar spindle
      apparatus. The Nuclear Mitotic Apparatus protein (NuMA) is recruited from
      interphase nuclei to spindle MTs during mitosis. The carboxy terminal domain of
      NuMA binds MTs, allowing a NuMA dimer to function as a "divalent" crosslinker
      that bundles MTs. The messenger RNA export factor, Rae1, also binds to MTs.
      Lowering Rae1 or increasing NuMA levels in cells results in spindle
      abnormalities. We have identified a mitotic-specific interaction between Rae1 and
      NuMA and have explored the relationship between Rae1 and NuMA in spindle
      formation. We have mapped a specific binding site for Rae1 on NuMA that would
      convert a NuMA dimer to a "tetravalent" crosslinker of MTs. In mitosis, reducing
      Rae1 or increasing NuMA concentration would be expected to alter the valency of
      NuMA toward MTs; the "density" of NuMA-MT crosslinks in these conditions would be
      diminished, even though a threshold number of crosslinks sufficient to stabilize
      aberrant multipolar spindles may form. Consistent with this interpretation, we
      found that coupling NuMA overexpression to Rae1 overexpression or coupling Rae1
      depletion to NuMA depletion prevented the formation of aberrant spindles.
      Likewise, we found that overexpression of the specific Rae1-binding domain of
      NuMA in HeLa cells led to aberrant spindle formation. These data point to the
      Rae1-NuMA interaction as a critical element for normal spindle formation in
      mitosis.

PMID- 17172456
TI  - Isolation of a multiheme protein with features of a hydrazine-oxidizing enzyme
      from an anaerobic ammonium-oxidizing enrichment culture.
AB  - A multiheme protein having hydrazine-oxidizing activity was purified from
      enriched culture from a reactor in which an anammox bacterium, strain KSU-1, was
      dominant. The enzyme has oxidizing activity toward hydrazine but not
      hydroxylamine and is a 130-kDa homodimer composed of a 62-kDa polypeptide
      containing eight hemes. It was therefore named hydrazine-oxidizing enzyme (HZO).
      With cytochrome c as an electron acceptor, the V(max) and K(m) for hydrazine are
      6.2 +/- 0.3 micromol/min.mg and 5.5 +/- 0.6 microM, respectively. Hydrazine (25
      microM) induced an increase in the proportion of reduced form in the spectrum,
      whereas hydroxylamine (500 microM) did not. Two genes coding for HZO, hzoA and
      hzoB, were identified within the metagenomic DNA from the culture. The genes
      encode the same amino acid sequence except for two residues. The sequences
      deduced from these genes showed low-level identities (<30%) to those of all of
      the hydroxylamine oxidoreductases reported but are highly homologous to two hao
      genes found by sequencing the genome of "Candidatus Kuenenia stuttgartiensis"
      (88% and 89% identities). The purified enzyme might therefore be a novel
      hydrazine-oxidizing enzyme having a critical role in anaerobic ammonium
      oxidation.

PMID- 17172457
TI  - Distribution and ecology of campylobacters in coastal plain streams (Georgia,
      United States of America).
AB  - Campylobacter is the leading cause of bacterium-associated diarrhea in the United
      States and most developed countries. While this disease is considered a food
      borne disease, many clinical cases cannot be linked to a food source. In rural
      and agrarian areas environmental transmission may be an important factor
      contributing to case loads. Here we investigated the waterborne prevalence of
      campylobacters in a mixed-use rural watershed in the coastal plain of southern
      Georgia (United States). Six sites representing various degrees of agricultural
      and human influence were surveyed biweekly to monthly for 1 year for the presence
      of culturable thermophilic campylobacters and other measures of water quality.
      Campylobacters were frequently present in agriculture- and sewage-impacted
      stretches of streams. The mean campylobacter counts and overall prevalence were
      highest downstream from a wastewater treatment plant that handled both human and
      poultry slaughterhouse waste (<or=595 CFU ml-1; 100% positive); the
      concentrations were significantly higher than those for the four upstream sites
      (P<0.05). The counts were significantly correlated with the number of fecal
      coliform bacteria, conductivity, pH, and concentrations of nutrients (NO3-,
      PO(4)3-, and NH3). Campylobacters were isolated more frequently and larger
      numbers were present during the summer months, similar to the occurrence of
      clinical cases of campylobacteriosis in this region. A multivariate model showed
      that the levels were significantly influenced by increasing precipitation, which
      also peaked in the summer. The results indicate that loading from both human and
      domestic animal waste may be high in the watershed studied during the summer
      months. Mixed-use watersheds supporting agriculture production, human
      populations, and wildlife may be at risk for contamination by campylobacters and
      may be an important route for human exposure.

PMID- 17172458
TI  - In situ biosurfactant production by Bacillus strains injected into a limestone
      petroleum reservoir.
AB  - Biosurfactant-mediated oil recovery may be an economic approach for recovery of
      significant amounts of oil entrapped in reservoirs, but evidence that
      biosurfactants can be produced in situ at concentrations needed to mobilize oil
      is lacking. We tested whether two Bacillus strains that produce lipopeptide
      biosurfactants can metabolize and produce their biosurfactants in an oil
      reservoir. Five wells that produce from the same Viola limestone formation were
      used. Two wells received an inoculum (a mixture of Bacillus strain RS-1 and
      Bacillus subtilis subsp. spizizenii NRRL B-23049) and nutrients (glucose, sodium
      nitrate, and trace metals), two wells received just nutrients, and one well
      received only formation water. Results showed in situ metabolism and
      biosurfactant production. The average concentration of lipopeptide biosurfactant
      in the produced fluids of the inoculated wells was about 90 mg/liter. This
      concentration is approximately nine times the minimum concentration required to
      mobilize entrapped oil from sandstone cores. Carbon dioxide, acetate, lactate,
      ethanol, and 2,3-butanediol were detected in the produced fluids of the
      inoculated wells. Only CO(2) and ethanol were detected in the produced fluids of
      the nutrient-only-treated wells. Microbiological and molecular data showed that
      the microorganisms injected into the formation were retrieved in the produced
      fluids of the inoculated wells. We provide essential data for modeling microbial
      oil recovery processes in situ, including growth rates (0.06 +/- 0.01 h(-1)),
      carbon balances (107% +/- 34%), biosurfactant production rates (0.02 +/- 0.001 h(
      1)), and biosurfactant yields (0.015 +/- 0.001 mol biosurfactant/mol glucose).
      The data demonstrate the technical feasibility of microbial processes for oil
      recovery.

PMID- 17172459
TI  - Identification of specific chemoattractants and genetic complementation of a
      Borrelia burgdorferi chemotaxis mutant: flow cytometry-based capillary tube
      chemotaxis assay.
AB  - Measuring the chemotactic response of Borrelia burgdorferi, the bacterial species
      that causes Lyme disease, is relatively more difficult than measuring that of
      other bacteria. Because these spirochetes have long generation times, enumerating
      cells that swim up a capillary tube containing an attractant by using colony
      counts is impractical. Furthermore, direct counts with a Petroff-Hausser chamber
      is problematic, as this method has a low throughput and necessitates a high cell
      density; the latter can lead to misinterpretation of results when assaying for
      specific attractants. Only rabbit serum and tick saliva have been reported to be
      chemoattractants for B. burgdorferi. These complex biological mixtures are
      limited in their utility for studying chemotaxis on a molecular level. Here we
      present a modified capillary tube chemotaxis assay for B. burgdorferi that
      enumerates cells by flow cytometry. Initial studies identified N
      acetylglucosamine as a chemoattractant. The assay was then optimized with respect
      to cell concentration, incubation time, motility buffer composition, and growth
      phase. Besides N-acetylglucosamine, glucosamine, glucosamine dimers (chitosan),
      glutamate, and glucose also elicited significant chemoattractant responses,
      although the response obtained with glucose was weak and variable. Serine and
      glycine were nonchemotactic. To further validate and to exploit the use of this
      assay, a previously described nonchemotactic cheA2 mutant was shown to be
      nonchemotactic by this assay; it also regained the wild-type phenotype when
      complemented in trans. This is the first report that identifies specific chemical
      attractants for B. burgdorferi and the use of flow cytometry for spirochete
      enumeration. The method should also be useful for assaying chemotaxis for other
      slow-growing prokaryotic species and in specific environments in nature.

PMID- 17172460
TI  - Gateway-based destination vectors for functional analyses of bacterial ORFeomes:
      application to the Min system in Brucella abortus.
AB  - Twenty Gateway-compatible destination vectors were constructed. The vectors
      comprise fluorescent and epitope fusion tags, various drug markers, and
      replication origins that should make them useful for exploring existing microbial
      ORFeomes. In an attempt to validate several of these vectors, we observed polar
      and oscillating localization of MinD in Brucella abortus.

PMID- 17172461
TI  - Effectiveness of disinfectants in killing Enterobacter sakazakii in suspension,
      dried on the surface of stainless steel, and in a biofilm.
AB  - The effectiveness of 13 disinfectants used in hospitals, day-care centers, and
      food service kitchens in killing Enterobacter sakazakii in suspension, dried on
      the surface of stainless steel, and in biofilm was determined. E. sakazakii
      exhibited various levels of resistance to the disinfectants, depending on the
      composition of the disinfectants, amount and type of organic matrix surrounding
      cells, and exposure time. Populations of planktonic cells suspended in water
      (7.22 to 7.40 log CFU/ml) decreased to undetectable levels (<0.30 log CFU/ml)
      within 1 to 5 min upon treatment with disinfectants, while numbers of cells in
      reconstituted infant formula were reduced by only 0.02 to 3.69 log CFU/ml after
      the treatment for 10 min. The presence of infant formula also enhanced the
      resistance to the disinfectants of cells dried on the surface of stainless steel.
      The resistance of cells to disinfectants in 6-day-old and 12-day-old biofilms on
      the surface of stainless steel was not significantly different. The overall order
      of efficacy of disinfectants in killing E. sakazakii was planktonic cells > cells
      inoculated and dried on stainless steel > cells in biofilms on stainless steel.
      Findings show that disinfectants routinely used in hospital, day-care, and food
      service kitchen settings are ineffective in killing some cells of E. sakazakii
      embedded in organic matrices.

PMID- 17172462
TI  - X-linked retinoschisis: an update.
AB  - X-linked retinoschisis is the leading cause of macular degeneration in males and
      leads to splitting within the inner retinal layers leading to visual
      deterioration. Many missense and protein truncating mutations have now been
      identified in the causative retinoschisis gene (RS1) which encodes a 224 amino
      acid secretory retinal protein, retinoschisin. Retinoschisin octamerisation is
      implicated in cell-cell interactions and cell adhesion perhaps by interacting
      with beta2 laminin. Mutations cause loss of retinoschisin function by one of the
      three mechanisms: by interfering with protein secretion, by preventing its
      octamerisation or by reducing function in the secreted octamerised protein. The
      development of retinoschisis mouse models have provided a model system that
      closely resembles the human disease. Recent reports of RS1 gene transfer to these
      models and the sustained restoration of some retinal function and morphology
      suggest gene replacement may be a possible future therapy for patients.

PMID- 17172464
TI  - Neurokinin-3 receptor-specific antagonists talnetant and osanetant show distinct
      mode of action in cellular Ca2+ mobilization but display similar binding kinetics
      and identical mechanism of binding in ligand cross-competition.
AB  - Talnetant and osanetant, two structurally diverse antagonists of neurokinin-3
      receptor (NK3), displayed distinct modes of action in Ca2+ mobilization. Although
      talnetant showed a normal Schild plot with a slope close to unity and a Kb
      similar to its Ki value in binding, osanetant presented an aberrant Schild with a
      steep slope (3.3 +/- 0.5) and a Kb value (12 nM) significantly elevated compared
      with its Ki value (0.8 nM) in binding. Kinetic binding experiments indicated a
      simple one-step binding mechanism with relatively fast on- and off-rates for both
      antagonists, arguing against slow onset of antagonism as the reason for abnormal
      Schild. This conclusion was supported by prolonged preincubation of antagonist
      that failed to improve the observed aberrant Schild. In ligand cross-competition
      binding, both talnetant and osanetant displayed linear reciprocal plots of
      identical slope when [MePhe7]neurokinin B (NKB) was used as the other competition
      partner with 125I-[MePhe7]NKB as the radioligand, indicating competitive binding
      of either antagonist with regard to [MePhe7]NKB. Similar patterns were obtained
      when talnetant was tested against osanetant, indicating competitive binding
      between the two antagonists as well. These results were reproduced when [3H]4
      quinolinecarboxamide (SB222200), a close derivative of talnetant, was used as the
      radioligand. Taken together, these data strongly suggest binding of both
      talnetant and osanetant at the orthosteric binding site with similar kinetic
      properties and do not support the hypothesis that the aberrant Schild observed in
      functional assays for osanetant is derived from differences in the mechanism of
      binding for these NK3 antagonists.

PMID- 17172463
TI  - Molecular characterisation of a mosaicism with a complex chromosome
      rearrangement: evidence for coincident chromosome healing by telomere capture and
      neo-telomere formation.
AB  - BACKGROUND: Broken chromosomes must acquire new telomeric "caps" to be
      structurally stable. Chromosome healing can be mediated either by telomerase
      through neo-telomere synthesis or by telomere capture. AIM: To unravel the
      mechanism(s) generating complex chromosomal mosaicisms and healing broken
      chromosomes. METHODS: G banding, array comparative genomic hybridization (aCGH),
      fluorescence in-situ hybridisation (FISH) and short tandem repeat analysis (STR)
      was performed on a girl presenting with mental retardation, facial dysmorphism,
      urogenital malformations and limb anomalies carrying a complex chromosomal
      mosaicism. RESULTS & DISCUSSION: The karyotype showed a de novo chromosome
      rearrangement with two cell lines: one cell line with a deletion 9pter and one
      cell line carrying an inverted duplication 9p and a non-reciprocal translocation
      5pter fragment. aCGH, FISH and STR analysis enabled the deduction of the most
      likely sequence of events generating this complex mosaic. During embryogenesis, a
      double-strand break occurred on the paternal chromosome 9. Following mitotic
      separation of both broken sister chromatids, one acquired a telomere vianeo
      telomere formation, while the other generated a dicentric chromosome which
      underwent breakage during anaphase, giving rise to the del inv dup(9) that was
      subsequently healed by chromosome 5 telomere capture. CONCLUSION: Broken
      chromosomes can coincidently be rescued by both telomere capture and neo-telomere
      synthesis.

PMID- 17172465
TI  - Probing HIV-1 integrase inhibitor binding sites with position-specific integrase
      DNA cross-linking assays.
AB  - HIV-1 integrase binds site-specifically to the ends of the viral cDNA. We used
      two HIV-1 integrase-DNA cross-linking assays to probe the binding sites of
      integrase inhibitors from different chemical families and with different strand
      transfer selectivities. The disulfide assay probes cross-linking between the
      integrase residue 148 and the 5'-terminal cytosine of the viral cDNA, and the
      Schiff base assay probes cross-linking between an integrase lysine residue and an
      abasic site placed at selected positions in the viral cDNA. Cross-linking
      interference by eight integrase inhibitors shows that the most potent cross
      linking inhibitors are 3'-processing inhibitors, indicating that cross-linking
      assays probe the donor viral cDNA (donor binding site). In contrast, strand
      transfer-selective inhibitors provide weak cross-linking interference, consistent
      with their binding to a specific acceptor (cellular DNA) site. Docking and
      crystal structure studies illustrate specific integrase-inhibitor contacts that
      prevent cross-linking formation. Four inhibitors that prevented Schiff base cross
      linking to the conserved 3'-terminal adenine position were examined for
      inhibition at various positions within the terminal 21 bases of the viral cDNA.
      Two of them selectively inhibited upper strand cross-linking, whereas the other
      two had a more global effect on integrase-DNA binding. These findings have
      implications for elucidating inhibitor binding sites and mechanisms of action.
      The cross-linking assays also provide clues to the molecular interactions between
      integrase and the viral cDNA.

PMID- 17172466
TI  - Reactive oxygen species and p38 mitogen-activated protein kinase activate Bax to
      induce mitochondrial cytochrome c release and apoptosis in response to malonate.
AB  - Malonate, an inhibitor of mitochondrial complex II, is a widely used toxin to
      study neurodegeneration in Huntington's disease and ischemic stroke. We have
      shown previously that malonate increased reactive oxygen species (ROS) production
      in human SH-SY5Y neuroblastoma cells, leading to oxidative stress, cytochrome c
      release, and apoptotic cell death. Expression of a green fluorescent protein-Bax
      fusion protein in SH-SY5Y neuroblastoma cells demonstrated a Bax redistribution
      from the cytosol to mitochondria after 12 to 24 h of malonate treatment that
      coincided with mitochondrial potential collapse and chromatin condensation.
      Inhibition of Bax translocation using furosemide, as well as Bax gene deletion,
      afforded significant protection against malonate-induced apoptosis. Further
      experiments revealed that malonate induced a prominent increase in the level of
      activated p38 mitogen-activated protein (MAP) kinase and that treatment with the
      p38 MAP kinase inhibitor SKF86002 potently blocked malonate-induced Bax
      translocation and apoptosis. Treatment with vitamin E diminished ROS production,
      reduced the activation status of p38 MAP kinase, inhibited Bax translocation, and
      protected against malonate-induced apoptosis. Our data suggest that malonate
      induced ROS production and subsequent p38 MAP kinase activation mediates the
      activation of the pro-apoptotic Bax protein to induce mitochondrial membrane
      permeabilization and neuronal apoptosis.

PMID- 17172467
TI  - Exchangers NCKX2, NCKX3, and NCKX4: identification of Thr-551 as a key residue in
      defining the apparent K(+) affinity of NCKX2.
AB  - K(+)-dependent Na(+)/Ca(2+) exchangers (NCKX) catalyze cytosolic Ca(2+) extrusion
      and are particularly important for neuronal Ca(2+) signaling. Of the five
      mammalian isoforms, the detailed functional characteristics have only been
      reported for NCKX1 and -2. In the current study, the functional characteristics
      of recombinant NCKX3 and -4 expressed in HEK293 cells were determined and
      compared with those of NCKX2. Although the apparent affinities of the three
      isoforms for Ca(2+) and Na(+) were similar, NCKX3 and -4 displayed approximately
      40-fold higher affinities for K(+) ions than NCKX2. Functional analysis of
      various NCKX2 mutants revealed that mutation of Thr-551 to Ala, the corresponding
      residue in NCKX4, resulted in an apparent K(+) affinity shift to one similar to
      that of NCKX4 without a parallel shift in apparent Ca(2+) affinity. In the
      converse situation, when Gln-476 of NCKX4 was converted to Lys, the corresponding
      residue in NCKX2, both the K(+) and Ca(2+) affinities were reduced. These results
      indicate that the apparently low K(+) affinity of NCKX2 requires a Thr residue at
      position 551 that may reduce the conformational flexibility and/or K(+) liganding
      strength of side-chain moieties on critical neighboring residues. This
      interaction appears to be specific to the structural context of the NCKX2 K(+)
      binding pocket, because it was not possible to recreate the K(+)-specific low
      affinity phenotype with reciprocal mutations in NCKX4. The results of this study
      provide important information about the structure and function of NCKX proteins
      and will be critical to understanding their roles in neuronal Ca(2+) signaling.

PMID- 17172468
TI  - The adenoviral E4orf6 protein induces atypical apoptosis in response to DNA
      damage.
AB  - Adenoviral proteins interact with host-cell proteins to either exploit or inhibit
      cellular functions for the purpose of viral propagation. E4orf6, the 34-kDa gene
      product of the E4 gene, interacts with the double-strand break repair (DSBR)
      protein DNA-dependent protein kinase and cooperates with binding partner E1B-55K
      to degrade MRE11, preventing viral DNA concatemer formation. We previously
      demonstrated that E4orf6 radiosensitizes human tumor cells through the inhibition
      of DSBR, notably in the absence of E1B-55K. Here, we report that E4orf6 prolongs
      the signaling of DNA damage by inhibiting the activity of protein phosphatase 2A
      (PP2A), the phosphatase responsible for dephosphorylating gammaH2AX. The
      inhibition of PP2A occurs without significant disruption of the DNA re-ligation
      rate. Prolonged signaling of DNA damage in the presence of E4orf6 initiates
      caspase-dependent and independent cell death. This is accompanied by poly(ADP
      ribose) polymerase (PARP) hyperactivation and the translocation of apoptosis
      inducing factor (AIF) from the mitochondria to the nucleus. Knockdown of AIF by
      shRNA rescues the radiosensitization induced by E4orf6. Taken together, these
      data suggest that E4orf6 disrupts cellular DSBR signaling by inhibiting PP2A,
      leading to prolonged H2AX phosphorylation, hyperactivation of PARP, and AIF
      translocation to the nucleus. The function of E4orf6 as an inhibitor of PP2A and
      activator of PARP in the absence of other adenoviral gene products is of
      importance in delineating the adenovirus-host cell interplay.

PMID- 17172469
TI  - Mechanical shedding of L-selectin from the neutrophil surface during rolling on
      sialyl Lewis x under flow.
AB  - The interaction of L-selectin expressed on leukocytes with endothelial cells
      leads to capture and rolling and is critical for the recruitment of leukocytes
      into sites of inflammation. It is known that leukocyte activation by
      chemoattractants, the change of osmotic pressure in cell media, or cross-linking
      of L-selectin all result in rapid shedding of L-selectin. Here we present a novel
      mechanism for surface cleavage of L-selectin on neutrophils during rolling on a
      sialyl Lewis x-coated surface that involves mechanical force. Flow cytometry and
      rolling of neutrophils labeled with Qdot(R)-L-selectin antibodies in an in vitro
      flow chamber showed that the mechanical shedding of L-selectin occurs during
      rolling and depends on the amount of shear applied. In addition, the mechanical L
      selectin shedding causes an increase in cell rolling velocity with rolling
      duration, suggesting a gradual loss of L-selectin and is mediated by p38 mitogen
      activated protein kinase activation. Thus, these data show that mechanical force
      induces the cleavage of L-selectin from the neutrophil surface during rolling and
      therefore decreases the adhesion of cells to a ligand-presenting surface in flow.

PMID- 17172470
TI  - Structural and kinetic evidence for an extended hydrogen-bonding network in
      catalysis of methyl group transfer. Role of an active site asparagine residue in
      activation of methyl transfer by methyltransferases.
AB  - The methyltetrahydrofolate (CH(3)-H(4)folate) corrinoid-iron-sulfur protein
      (CFeSP) methyltransferase (MeTr) catalyzes transfer of the methyl group of CH(3)
      H(4)folate to cob(I)amide. This key step in anaerobic CO and CO(2) fixation is
      similar to the first half-reaction in the mechanisms of other cobalamin-dependent
      methyltransferases. Methyl transfer requires electrophilic activation of the
      methyl group of CH(3)-H(4)folate, which includes proton transfer to the N5 group
      of the pterin ring and poises the methyl group for reaction with the Co(I)
      nucleophile. The structure of the binary CH(3)-H(4)folate/MeTr complex (revealed
      here) lacks any obvious proton donor near the N5 group. Instead, an Asn residue
      and water molecules are found within H-bonding distance of N5. Structural and
      kinetic experiments described here are consistent with the involvement of an
      extended H-bonding network in proton transfer to N5 of the folate that includes
      an Asn (Asn-199 in MeTr), a conserved Asp (Asp-160), and a water molecule. This
      situation is reminiscent of purine nucleoside phosphorylase, which involves
      protonation of the purine N7 in the transition state and is accomplished by an
      extended H-bond network that includes water molecules, a Glu residue, and an Asn
      residue (Kicska, G. A., Tyler, P. C., Evans, G. B., Furneaux, R. H., Shi, W.,
      Fedorov, A., Lewandowicz, A., Cahill, S. M., Almo, S. C., and Schramm, V. L.
      (2002) Biochemistry 41, 14489-14498). In MeTr, the Asn residue swings from a
      distant position to within H-bonding distance of the N5 atom upon CH(3)
      H(4)folate binding. An N199A variant exhibits only approximately 20-fold weakened
      affinity for CH(3)-H(4)folate but a much more marked 20,000-40,000-fold effect on
      catalysis, suggesting that Asn-199 plays an important role in stabilizing a
      transition state or high energy intermediate for methyl transfer.

PMID- 17172471
TI  - Iron causes interactions of TAK1, p21ras, and phosphatidylinositol 3-kinase in
      caveolae to activate IkappaB kinase in hepatic macrophages.
AB  - We recently discovered a novel signaling phenomenon involving a rapid and
      transient rise in intracellular low molecular weight iron complex(es) in
      activation of IkappaB kinase (IKK) in hepatic macrophages. We also showed direct
      treatment with ferrous iron substitutes for this event to activate IKK. The
      present study used this model to identify upstream kinases responsible for IKK
      activation. IKK activation induced by iron is abrogated by overexpression of a
      dominant negative mutant (DN) for transforming growth factor beta-activated
      kinase-1 (TAK1), NF-kappaB-inducing kinase, or phosphatidylinositol 3-kinase
      (PI3K) and by treatment with the mitogen-activated protein kinase (MAPK) kinase-1
      (MEK1) inhibitor. Iron increases AKT phosphorylation that is prevented by DNTAK1
      or DNp21ras. Iron causes ERK1/2 phosphorylation that is attenuated by DN-PI3K,
      prevented by DNp21ras, but unaffected by DNTAK1. Iron-induced TAK1 activity is
      not affected by the PI3K or MEK1 inhibitor, suggesting TAK1 is upstream of PI3K
      and MEK1. Iron increases interactions of TAK1 and PI3K with p21ras as
      demonstrated by co-immunoprecipitation and co-localization of these proteins with
      caveolin-1 as shown by immunofluorescent microscopy. Finally, filipin III, a
      caveolae inhibitor, abrogates iron-induced TAK1 and IKK activation. In
      conclusion, MEK1, TAK1, NF-kappa-inducing kinase, and PI3K are required for iron
      induced IKK activation in hepatic macrophages and TAK1, PI3K, and p21ras
      physically interact in caveolae to initiate signal transduction.

PMID- 17172472
TI  - HIV-1 reverse transcriptase plus-strand initiation exhibits preferential
      sensitivity to non-nucleoside reverse transcriptase inhibitors in vitro.
AB  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are highly specific and
      potent allosteric inhibitors of human immunodeficiency virus type 1 (HIV-1)
      reverse transcriptase. NNRTIs inhibit reverse transcription in a substrate length
      dependent manner in biochemical assays and in cell-based HIV-1 replication
      assays, suggesting a stochastic inhibitory mechanism. Surprisingly, we observed
      that NNRTIs potently inhibited plus-strand initiation in vitro under conditions
      in which little or no inhibition of minus-strand DNA synthesis was observed. In
      assays that recapitulated the initiation of plus-strand DNA synthesis, greater
      inhibition was observed with an RNA PPT primer than with a DNA primer of
      corresponding sequence and with wild-type reverse transcriptase but not with
      NNRTI-resistant enzymes. Structural elements that dictate sensitivity to NNRTIs
      were revealed using modified plus-strand initiation substrates. The data
      presented here suggest that specific inhibition of plus-strand initiation may be
      an important mechanism by which NNRTIs block HIV-1 replication.

PMID- 17172473
TI  - Sequential WT1 and CTNNB1 mutations and alterations of beta-catenin localisation
      in intralobar nephrogenic rests and associated Wilms tumours: two case studies.
AB  - BACKGROUND: Intralobar nephrogenic rests (ILNRs) are precursor lesions for Wilms
      tumours and are associated with WT1 gene mutations. ILNR-associated Wilms tumours
      have a co-clustering of WT1 and beta-catenin (CTNNB1) mutations and unique
      histological features characterised by a stromal-predominant histology. AIM: To
      determine the order in which WT1 and CTNNB1 mutations occur to understand the
      ILNR-Wilms tumour sequence. METHODS: Of nine Wilms tumours with WT1 and CTNNB1
      mutations, three ILNRs lesions in two Wilms tumours were available for analysis
      of WT1 and CTNNB1 mutations using microdissection. Immunohistochemistry was also
      performed to investigate how the mutations in beta-catenin alter the localisation
      in Wilms tumour development. RESULTS: WT1 mutations were present in the ILNRs,
      however CTNNB1 mutations were absent. Immunohistochemistry for WT1 confirmed
      inactivation of WT1 in both ILNRs and Wilms tumours. Both the ILNRs and the
      associated Wilms tumours had similar immunostaining patterns for beta-catenin in
      the blastemal and epithelial components. Although rhabdomyoblasts were not
      included in ILNRs, the associated Wilms tumours showed rhabdomyogenic
      differentiation with a positive beta-catenin nuclear staining. CONCLUSIONS: The
      results suggest that CTNNB1 mutation is a later event in Wilms tumourigenesis.
      CTNNB1 mutations might be associated with rhabdomyogenesis.

PMID- 17172474
TI  - Reversing the slow death of the clinical necropsy: developing the post of the
      Pathology Liaison Nurse.
AB  - The adult clinical necropsy has been declining for many years and is nearing
      extinction in many hospitals. In Norwich, to prevent this from occurring, a
      Pathology Liaison Nurse (PLN) was appointed, resulting in a modest reversal of
      the trend. In 2005, the number of adult clinical necropsies increased to 58
      (clinical necropsy rate = 2.4%) from its nadir of 34 (clinical necropsy rate =
      1.4%) in 2003. Moreover, consent is now much more likely to be full and to allow
      histopathological and other studies. The PLN ensures that consent is properly and
      fully obtained, in line with current legislation. She also plays an important
      role in arranging for feedback to be given by clinicians to the families after
      the examination, and in teaching and training Trust staff about death,
      bereavement, and related matters. This paper describes how the role of PLN was
      established and evaluated, and gives details of the current state of the adult
      clinical necropsy in Norwich.

PMID- 17172477
TI  - Plasma concentrations of parathyroid hormone-related protein in dogs with
      potential disorders of calcium metabolism.
AB  - The plasma concentrations of total calcium, ionised calcium, albumin, parathyroid
      hormone and parathyroid hormone-related protein (PTHrp) were measured in 25 dogs
      with lymphoma, nine dogs with primary hyperparathyroidism and seven dogs with
      adenocarcinoma of the apocrine gland of the anal sac. Plasma total calcium,
      ionised calcium, albumin and parathyroid hormone-related protein were measured in
      18 clinically normal control dogs. The concentration of PTHrp was high in 12 of
      the 14 dogs that were hypercalcaemic because of an underlying malignancy but was
      within the reference range in all the control dogs, in the 17 normocalcaemic dogs
      with lymphoma and in the seven dogs which were hypercalcaemic because of a
      parathyroid adenoma.

PMID- 17172476
TI  - Best practice in primary care pathology: review 8.
AB  - This eighth best practice review examines four series of common primary care
      questions in laboratory medicine: (i) sodium abnormalities; (ii) faecal occult
      blood testing; (iii) warfarin management; and (iv) sputum cytology in diagnosis
      of bronchopulmonary malignancy. The review is presented in question-answer
      format, referenced for each question series. The recommendations represent a
      precis of guidance found using a standardised literature search of national and
      international guidance notes, consensus statements, health policy documents and
      evidence-based medicine reviews, supplemented by Medline Embase searches to
      identify relevant primary research documents. They are not standards but form a
      guide to be set in the clinical context. Most are consensus rather than evidence
      based. They will be updated periodically to take account of new information.

PMID- 17172475
TI  - The significance of substance P in physiological and malignant haematopoiesis.
AB  - The role of substance P (SP) in physiological haematopoiesis is well established.
      However, it also seems to be important in the neoplastic transformation of bone
      marrow, leading to the development of acute leukaemia in children, and also
      metastases to bone marrow of solid tumours (particularly neuroblastoma and breast
      cancer) in early stages of these diseases. This review summarises the available
      data on SP involvement in both processes. In the future, SP antagonists may be
      used as anti-neoplastic drugs, for example by direct or indirect blocking of
      tumour cell proliferation through inhibition of growth factor production and
      interleukin-1b synthesis.

PMID- 17172478
TI  - Biological variation, individuality and critical differences of eight biochemical
      blood constituents in budgerigars (Melopsittacus undulatus).
AB  - The aim of the study was to obtain basic data on individual biological variation,
      the required number of specimens to define the homeostatic setpoint (the aspired
      value of a variable adjusted to the individuals homeostasis) and critical
      differences of selected chemistry parameters in budgerigars (Melopsittacus
      undulatus). Blood from 99 healthy budgerigars was sampled 12 times at four-week
      intervals. Aspartate aminotransferase (ast), calcium, creatine kinase (ck),
      glutamate dehydrogenase (gldh), glucose, lactate dehydrogenase (ldh), total
      protein and uric acid were investigated. The indices of individuality obtained in
      the present study were relatively low (total protein 0.93, ast 1.02, gldh 1.04,
      ck 1.12, ldh 1.24, uric acid 1.26, glucose 1.39, calcium 1.61) and suggest that
      population-based reference limits might be useful. Comparison of data showed that
      the application of intraindividual reference values identified much greater
      variation in the reference values than using conventional population-based
      reference limits. Otherwise, the moderate to low degrees of individuality may
      allow the use of reference values of one individual as a standard for another
      individual of the same species. The critical differences that define the change
      needed between two serial results to indicate a biological change was highest in
      gldh with 120 per cent or 1.7 U/l. In calcium, a change of 30.5 per cent or 0.5
      mmol/l would be significant. In the other parameters critical differences varied
      between 38 per cent in glucose, up to 93 per cent in uric acid.

PMID- 17172479
TI  - Effects of coitus and the artificial insemination of different volumes of fresh
      semen on uterine contractions in mares.
AB  - Uterine contractions may play an important role in the transportation of
      spermatozoa towards the site of fertilisation in the oviduct of mares. M-mode
      ultrasound was used to measure the number, amplitude and duration of uterine
      contractions in each uterine horn and the uterine body of oestrous mares for four
      minutes before and four minutes after either coitus, or the artificial
      insemination of either 80.0 ml of fresh semen or 10.0 ml of fresh semen. The
      direction of the uterine contractions in each uterine horn and the uterine body
      was measured before and after coitus. Coitus and the insemination of 80.0 ml
      semen significantly increased the total number, mean amplitude and mean duration
      of contractions in all parts of the uterus. The insemination of 10.0 ml of semen
      did not affect the total number or the mean duration of contractions in the
      uterine horns. Their mean amplitude was increased, but largely owing to the
      results from one mare; it also did not affect the contractions in the uterine
      body. There was no significant difference between the percentage of contractions
      moving in a cervicotubal or tubocervical direction after coitus in any part of
      the uterus examined.

PMID- 17172480
TI  - Seroprevalence to chlamydiae in pigs in Italy.

PMID- 17172481
TI  - Nephroblastoma in an adult sheep.

PMID- 17172483
TI  - Influence of food intake on the clinical response to cyclosporin A in canine
      atopic dermatitis.

PMID- 17172482
TI  - Epidemiological study of hepatitis E virus infection of dogs and cats in Japan.

PMID- 17172485
TI  - Support network for recent graduates.

PMID- 17172484
TI  - Equine interspecies aggression.

PMID- 17172486
TI  - Oak poisoning in cattle.

PMID- 17172487
TI  - Botulism in cattle.

PMID- 17172489
TI  - Equine interspecies aggression.

PMID- 17172488
TI  - Anthelmintic resistance in sheep flocks in Wales.

PMID- 17172490
TI  - Digital images of case reports and other articles.

PMID- 17172491
TI  - Expression of p21WAF in salivary gland mucoepidermoid carcinoma and its relation
      to histologic grade.
AB  - The biologic behavior and factors influencing the development of salivary gland
      mucoepidermoid carcinoma are not fully understood. Alteration of the cyclin
      dependant kinase inhibitor p21(WAF) could cause uncontrolled proliferation
      leading to cancer. Thirty-five mucoepidermoid carcinomas were graded and
      immunohistochemically stained for p21(WAF). The percentage of positive tumor
      cells was determined using an eyepiece graticule and a computer-assisted image
      analyzer, which revealed 8.6% and 22.9% of the cases to be positive for p21(WAF),
      respectively. A statistically significant correlation was not observed between
      p21(WAF) and grading. Considering the absence of p21(WAF) expression in most
      mucoepidermoid carcinomas, it appears that the inhibitory effect of p21(WAF) on
      cell growth is removed in most cases. Given the lack of correlation with tumor
      grade, it is possible that the impact of p21(WAF) is in the earlier stages of
      tumorigenesis. A p53-independent pathway of p21(WAF) induction may exist for the
      small proportion of tumors that showed positivity.

PMID- 17172492
TI  - Breast tumor resembling the tall cell variant of papillary thyroid carcinoma:
      report of 4 cases with evidence of malignant potential.
AB  - A new type of breast carcinoma resembling the tall cell variant of papillary
      thyroid carcinoma has recently been described. To date, rare cases are on record.
      Here, 4 new cases of the tall cell variant of papillary thyroid carcinoma of the
      breast are described in women aged from 45 to 80 years old. All patients
      presented with palpable breast nodules and were treated with quadrantectomy. One
      patient presented with a long clinical history and a metastatic intramammary
      lymph node. The patient is alive and well 3 months after surgery. The remaining 3
      patients are disease free at mean 7.5 months (range, 5 to 10 months) after
      surgery. These data suggest that papillary thyroid-like carcinomas of the breast
      show malignant potential.

PMID- 17172493
TI  - Rhabdomyoblastic differentiation in malignant melanoma in adults: report of 2
      cases.
AB  - Two cases of malignant melanoma are reported in adults exhibiting
      rhabdomyoblastic differentiation to alert pathologists to this rare variant of
      malignant melanoma. One of the cases presented as a metastasis in a submandibular
      lymph node, and the other was a primary skin melanoma. There are only a few
      published reports on melanocytic tumors with rhabdomyoblastic differentiation,
      mainly occurring in giant congenital nevi. Both cases reported here were
      confirmed by immunohistochemistry. Both cases were also studied by electron
      microscopy, and one showed distinctive ultrastructural features of striated
      muscle.

PMID- 17172494
TI  - Incidental rectal mucosa obtained via transrectal ultrasound-guided prostatic
      core biopsies.
AB  - A retrospective review was conducted of material from 782 transrectal ultrasound
      guided prostatic core biopsies to determine whether incidental pieces of rectal
      mucosa obtained in this manner could harbor clinically significant rectal
      pathology or incur artifacts that cause diagnostic difficulty. Material from 114
      biopsies (14.6%) showed rectal mucosa, and material from 19 (16.7%) showed rectal
      pathology, including a hyper-plastic polyp in 1, changes consistent with
      ulcerative proctitis in 8, focal active proctitis in 7, and granulomas in 3. The
      original pathologist overlooked the hyperplastic polyp. In 1 specimen, rectal
      lymphocytes and plasma cells that were displaced over prostatic tissue closely
      mimicked prostatic adenocarcinoma (Gleason score 5). Conversely, in another
      specimen, prostatic adenocarcinoma (Gleason score 5) that was displaced near
      rectal mucosa closely mimicked a rectal lymphoid aggregate. Incidental rectal
      mucosa obtained via transrectal ultrasound-guided prostatic core biopsies
      occasionally harbors clinically significant rectal pathology and rarely incurs
      artifacts that cause diagnostic difficulty.

PMID- 17172495
TI  - Intramucosal ganglion cells in normal adult colorectal mucosa.
AB  - Intramucosal ganglion cells are incompletely understood. Reviewed were 100 normal
      specimens from colorectal biopsies of nonconstipated adults to firmly establish
      the existence of intramucosal ganglion cells in normal adult colorectal mucosa,
      determine whether intramucosal giant ganglia exist, and compare the prevalence of
      colorectal intramucosal ganglion cells between men and women. Fifty specimens
      from each gender were examined. Twenty specimens contained intramucosal ganglion
      cells, including 15 from women (75%) and only 5 from men (25%). Intramucosal
      ganglion cells occurred singly or in clusters. One woman had large disciform and
      globular clusters with 7 ganglion cells, resembling giant ganglia. Awareness of
      ganglion cells and large ganglia in normal mucosa is necessary to avoid potential
      confusion with ectopic ganglion cells and submucosal giant ganglia seen in adult
      intestinal neuronal dysplasia. Intramucosal ganglion cells in normal colorectal
      mucosa are particularly common in women. This disparity might contribute to
      colorectal neurophysiologic differences between genders.

PMID- 17172496
TI  - The histopathologic spectrum of carcinomas involving the gastroesophageal
      junction in the Chinese.
AB  - Carcinomas involving the gastroesophageal junction are common in China. The
      histopathologic characteristics of these cancers have not been systematically
      investigated. Reported are 41 such resected cancers from Chinese patients (30
      men, 11 women). Their mean age was 62 years. The mean tumor size was 4.4 cm
      (range, 2 to 9 cm), and 58% were poorly differentiated. An unusual spectrum of
      tumor differentiation was observed, including adenocarcinomas (83%),
      adenosquamous (32%), colloid (2%), signet-ring (10%), squamous (5%), oncocytic
      (7%), pancreatic acinar (12%), and neuroendocrine (5%) carcinomas. Cancers with
      multiple types of differentiation in the same tumor were identified in 37 cases
      (90%). The adjacent gastric cardiac mucosa showed hyperplasia, oncocytic, and
      pancreatic acinar metaplasia, and mild chronic inflammation. Dysplasia was
      uncommon (n = 6). Barrett esophagus was not identified. Carcinomas involving the
      gastroesophageal junction in the Chinese are morphologically distinct,
      heterogeneous, and may be of esophageal origin.

PMID- 17172497
TI  - Artefact as the pathologist's friend: peritumoral retraction in in situ and
      infiltrating duct carcinoma of the breast.
AB  - Peritumoral retraction artefact appears in tissue sections as an empty space
      partially or completely encircling a nest of tumor cells, usually in conformity
      with the rounded or angular outline of that particular nest. The present study
      was designed to test this finding in a large series of cases and to quantify the
      appearance of peritumoral retraction artefact in, in situ and infiltrating duct
      carcinoma of the breast. We examined 199 cases of infiltrating duct carcinoma
      (IDC) and 188 cases of ductal carcinoma in situ (DCIS). Of the total of 387
      cases, 111 were core needle biopsies, whereas the others were larger resections.
      In each specimen, retraction was evaluated on hematoxylin and eosin-stained
      slides as negative, 1+ (1% to 25% of tumor showing retraction), 2+ (26% to 50%),
      3+ (51% to 75%), or 4+ (76% to 100%). Overall, peritumoral retraction was noted
      in 168 of 199 cases (84.4%) of IDC, versus 30 of 188 cases (16%) of DCIS (P <
      0.0001). Peritumoral retraction scored as 2+ or greater (26% to 50%) was seen in
      only 1 of 188 DCIS specimens, compared with 77 of 199 IDC. Thus, peritumoral
      retraction artefact appears to be a significant finding seen during the
      evaluation of hematoxylin and eosin specimens for the diagnosis of carcinoma. We
      discuss the possibility that this phenomenon might represent true prelymphatic
      space involvement rather than a fixation artefact.

PMID- 17172498
TI  - Renal medullary dysplasia is diagnostic of Beckwith-Wiedemann syndrome.

PMID- 17172499
TI  - Lobomycosis.

PMID- 17172500
TI  - Brunner gland cyst.

PMID- 17172501
TI  - Dry fruit bezoar causing acute small intestinal obstruction.

PMID- 17172502
TI  - Fishing for vascular invasion.

PMID- 17172503
TI  - Nodular fasciitis of the male breast: a case report.
AB  - A case of nodular fasciitis is reported that involved the breast parenchyma of a
      40-year-old man. The differential diagnosis of nodular fasciitis in the male
      breast mainly includes fibromatosis and myofibroblastoma. However, other benign
      and malignant spindle cell lesions of the breast, such as pseudoangiomatous
      stromal hyperplasia and especially spindle cell metaplastic carcinoma and
      fibrosarcoma, may enter the differential. The classic histomorphologic features
      and immunohistochemical findings are helpful in arriving at the correct
      diagnosis. The patient underwent a total excision of the lesion and is free of
      disease after 14 months. To our knowledge, this is the first reported case of a
      lesion of this type in the male breast.

PMID- 17172504
TI  - Polypoid dermal dendrocytic hamartoma in a giant congenital melanocytic nevus.
AB  - Giant congenital melanocytic nevus (CMN) might be complicated by the development
      of several tumor types, mainly melanoma and rhabdomyosarcoma, but also poorly
      differentiated neoplasms. Striking polypoid exophytic masses occasionally result
      from neuroectodermal and neuromesenchymal hamartomatous overgrowths, which lends
      support to the concept of pluripotential melanoblastomatous and neurocristic
      origin of these lesions. The present report describes what appears to be a unique
      example of dermal hamartomatous polypoid CD34(+) fibrogenic proliferation devoid
      of melanin, namely a dendrocytoma, surrounded by the melanocytes from the nevus,
      located in the skin of the scrotum against a background of giant CMN. The
      differential diagnosis included dermatofibrosarcoma protuberans, giant-cell
      fibroblastoma, angiofibroma, Bednar tumor, other types of dermal dendrocytic
      hamartoma, and neurocristic cutaneous hamartoma. This case lends support to the
      proposed neurocristic origin of dermal fibrogenic cells.

PMID- 17172505
TI  - Oncocytic meningioma: report of a case with progression after radiosurgery.
AB  - Oncocytic meningioma is an uncommon variant of meningioma, characterized
      histologically by cells rich in mitochondria. This subtype of meningioma needs to
      be distinguished from other types of meningioma because of its more aggressive
      behavior. A case of oncocytic meningioma showing rapid clinical progression with
      diffuse intracranial dissemination after radiosurgery is described. Resistance to
      radiotherapy has been previously reported in oncocytic tumors of various body
      sites. This new case is a further example of the greater aggressiveness of
      oncocytic meningioma, suggesting that radiation therapy might worsen the course
      of disease.

PMID- 17172506
TI  - A unique simultaneous occurrence of paratracheal granular cell tumor and
      papillary thyroid carcinoma.
AB  - We report an unusual case of granular cell tumor in the paratracheal region
      detected during total thyroidectomy for papillary carcinoma and clinically
      misdiagnosed as tracheal infiltration of thyroid neoplasia. Histologically, the
      granular cell tumor had infiltrated the thyroid gland close behind the papillary
      carcinoma. At immunohistochemical investigation, the cells showed diffuse
      positivity for S-100, neuron-specific enolase, and CD68, and surprisingly,
      positivity also for galectin-3 and HBME-1. A granular cell tumor should also be
      considered in the cytologic differential diagnosis of the thyroid and
      paratracheal nodules.

PMID- 17172507
TI  - Malakoplakia of the prostate on needle core biopsy: a case report and review of
      the literature.
AB  - Malakoplakia is a rare inflammatory disorder that results from an infectious
      process and that may be associated with immunosuppression. It most often occurs
      in the genitourinary tract; however, isolated cases have been reported in many
      other organs, including colon, stomach, lung, liver, bone, uterus, and skin. In
      the bladder, which is the most common site of involvement, it may be mistaken for
      malignancy on cystoscopic examination or computerized topography scan. Gram
      negative bacteria such as Escherichia coli and Klebsiella pneumonia are often
      isolated from malakoplakia lesions, although other less common bacteria such as
      Rhodococcus equi may also be found. This is a case report of prostatic
      malakoplakia diagnosed on needle core biopsy from a patient suspected to harbor a
      malignancy.

PMID- 17172508
TI  - The threat from Balamuthia mandrillaris.

PMID- 17172509
TI  - Enteroaggregative Escherichia coli: epidemiology, virulence and detection.
AB  - Enteroaggregative Escherichia coli (EAEC) is a subgroup of diarrhoeagenic E. coli
      (DEC) that during the past decade has received increasing attention as a cause of
      watery diarrhoea, which is often persistent. EAEC have been isolated from
      children and adults worldwide. As well as sporadic cases, outbreaks of EAEC
      caused diarrhoea have been described. The definition of EAEC is the ability of
      the micro-organism to adhere to epithelial cells such as HEp-2 in a very
      characteristic 'stacked-brick' pattern. Although many studies searching for
      specific virulence factor(s) unique for this category of DEC have been published
      it is still unknown why the EAEC cause persistent diarrhoea. In addition, the
      aggregative property of EAEC causes a lot of problems in serotyping due to the
      cells auto-agglutinating. The gold standard for identification of EAEC includes
      isolation of the agent and an adherence assay using tissue culture, viz. HEp-2
      cells. This assay is in most cases reliable; however, emergence of 'atypical'
      EAEC has been described in several publications. In addition, the HEp-2 assay is
      time consuming, demands a tissue culture lab and trained staff. Several molecular
      biological assays have been described, however, none show 100 % specificity.

PMID- 17172510
TI  - Helicobacter pylori cag pathogenicity island genes: clinical relevance for peptic
      ulcer disease development in Brazil.
AB  - The purpose of this study was to verify whether the presence of any of the
      Helicobacter pylori cagPAI genes or segments--cagA, cagA promoter, cagE, cagM,
      tnpB, tnpA, cagT and the left end of the cag II (LEC) region--would be a useful
      marker for the risk of peptic ulcer disease development. H. pylori DNA extracted
      from positive urease tests of 150 peptic ulcer patients and 65 dyspeptic controls
      was analysed by PCR. Duodenal ulcers were present in 110, gastric ulcers in 23
      and both gastric and duodenal ulcers in 17 patients. A significant association (P
      <0.001) was found between a conserved cagPAI and peptic ulcer disease (34 %). The
      positivity of the cagA gene varied according to the region of the gene that was
      amplified. The region near to the promoter was present in almost all of the H.
      pylori isolates (97.2 %). The segment from nt 1764 to 2083 and the extreme right
      end were frequently deleted in the isolates from the controls (P <0.01). The
      positivity of the promoter region of cagA and cagT, cagE, cagM and LEC showed a
      significant difference between the isolates from peptic ulcer patients and from
      the controls (P <0.01). Patients usually had moderate gastritis; however, the
      intensity of the active inflammation was higher in the peptic ulcer group (P
      <0.001). cagT, cagM, LEC and the right end terminus of the cagA-positive H.
      pylori isolates were associated with a 27-fold, 8-fold, 4-fold and 4-fold risk of
      peptic ulcer disease, respectively, and may be useful markers to identify
      individuals at higher risk of peptic ulcer disease development in Brazil.

PMID- 17172511
TI  - Chlamydia trachomatis OmcB protein is a surface-exposed glycosaminoglycan
      dependent adhesin.
AB  - The OmcB protein of Chlamydia trachomatis is a cysteine-rich outer membrane
      polypeptide with important functional, structural and antigenic properties. The
      entire gene encoding the OmcB protein from C. trachomatis serovar LGV1 was cloned
      and expressed in Escherichia coli and the full-length protein used to raise
      polyclonal antibodies. Recombinant OmcB was used to show that OmcB is a surface
      exposed protein that functions as a chlamydial adhesin. Infectivity inhibition
      assays carried out using HeLa cells with serovar LGV1 in the presence of purified
      anti-OmcB serum showed inhibition of infectivity, suggesting that some of the
      OmcB was surface exposed. Moreover, using recombinant OmcB in infectivity
      inhibition assays resulted in 70% inhibition of infectivity, confirming that OmcB
      plays a role as an adhesin in C. trachomatis. Furthermore, recombinant OmcB
      protein bound to the surface of HeLa and Hec1B cells, but binding to
      glycosaminoglycan (GAG)-deficient cells (pgsA-745 and pgsD-677) was markedly
      reduced, indicating that OmcB binds to GAG-like receptors on host cells.

PMID- 17172512
TI  - Cell adherence-promoted activity of Plesiomonas shigelloides groEL.
AB  - Previously, it has been demonstrated that the invasion of Caco-2 cells by
      Plesiomonas shigelloides induces apoptotic cell death. Therefore, the attachment
      to and colonization of eukaryotic intestinal host cells by P. shigelloides are
      important steps in causing pathogenicity. In this study, the participation of P.
      shigelloides GroEL in the attachment of P. shigelloides was examined. The groESL
      operon of P. shigelloides was isolated by PCR. The nucleotide sequence of the
      groESL operon of P. shigelloides revealed two ORFs of 294 nucleotides for groES
      and 1647 nucleotides for groEL. Cell fractionation and immunostaining experiments
      suggested that the GroEL of P. shigelloides was associated with the bacterial
      cell surface. The expression of the groEL gene was upregulated during the
      attachment and apoptosis-induction stages, and the expression of the protein was
      also induced during the attachment stage. Furthermore, GroEL efficiently promoted
      the attachment of P. shigelloides to Caco-2 cells, as measured by a FACSCalibur
      flow cytometer. These results demonstrated that GroEL has a positive influence on
      the attachment of P. shigelloides to Caco-2 cells.

PMID- 17172513
TI  - Effects of human serum on Balamuthia mandrillaris interactions with human brain
      microvascular endothelial cells.
AB  - Balamuthia mandrillaris is a free-living amoeba and a causative agent of fatal
      granulomatous encephalitis. In the transmission of B. mandrillaris into the
      central nervous system (CNS), haematogenous spread is thought to be the primary
      step, followed by blood-brain barrier penetration. The objectives of the present
      study were (i) to determine the effects of serum from healthy individuals on the
      viability of B. mandrillaris, and (ii) to determine the effects of serum on B.
      mandrillaris-mediated blood-brain barrier perturbations. It was determined that
      normal human serum exhibited limited amoebicidal effects, i.e. approximately 40 %
      of trophozoites were killed. The residual subpopulation, although viable,
      remained static over longer incubations. Using human brain microvascular
      endothelial cells (HBMEC), which form the blood-brain barrier, it was observed
      that B. mandrillaris exhibited binding (>80 %) and cytotoxicity (>70 %) to HBMEC.
      However, normal human serum exhibited more than 60 % inhibition of B.
      mandrillaris binding and cytotoxicity to HBMEC. ELISAs showed that both serum and
      saliva samples exhibit the presence of anti-B. mandrillaris antibodies. Western
      blots revealed that normal human serum reacted with several B. mandrillaris
      antigens with approximate molecular masses of 148, 115, 82, 67, 60, 56, 44, 42,
      40 and 37 kDa. Overall, the results demonstrated that normal human serum has
      inhibitory effects on B. mandrillaris growth and viability, as well as on their
      binding and subsequent cytotoxicity to HBMEC. A complete understanding of B.
      mandrillaris pathogenesis is crucial to develop therapeutic interventions and/or
      to design preventative measures.

PMID- 17172514
TI  - Evaluation of real-time PCR and conventional diagnostic methods for the detection
      of Clostridium difficile-associated diarrhoea in a prospective multicentre study.
AB  - In this prospective multicentre study, an enzyme-linked fluorescent assay (VIDAS
      CDA2; bioMerieux), an enzyme-linked assay [Premier Toxins A and B (PTAB);
      Meridian] and an in-house real-time PCR amplifying the tcdB gene were compared
      with the cell cytotoxicity assay used as the 'gold standard' for diagnosis of
      Clostridium difficile-associated diarrhoea (CDAD). Faecal samples from patients
      with a request for C. difficile diagnosis and samples from patients with
      diarrhoea hospitalized for at least 72 h were collected for 3 consecutive months
      from four university medical centres in The Netherlands. In total, 547 faecal
      samples were obtained from 450 patients. Of 540 samples available for all of the
      assays, 84 (15.6 %) showed a positive result in one or more assays. The cell
      cytotoxicity assay was positive in 31 samples (5.7 %) from 28 patients. A
      diagnosis of CDAD was not considered by the physician in 5 (23.8 %) of 21
      patients with CDAD who were hospitalized for at least 72 h. Compared with the
      cell cytotoxicity assay, the sensitivity of VIDAS, PTAB and PCR was 83.9, 96.8
      and 87.1 %, respectively. The specificity of VIDAS, PTAB and PCR was 97.1, 94.3
      and 96.5 %, respectively. The positive and negative predictive values for VIDAS,
      PTAB and PCR were 63.4 and 99.0 %, 50.9 and 99.8 %, and 60.0 and 99.2 %,
      respectively. Of 61 samples that were positive in one, two or three of the
      assays, 56 were available for discordance analysis. Discordance analysis was
      performed by culture of toxinogenic strains. The concordance of VIDAS, PTAB and
      PCR with culture was 53.6 % (30/56), 55.4 % (31/56) and 71.4 % (40/56),
      respectively. It was concluded that real-time PCR had the highest concordance
      with toxinogenic culture and is therefore the preferred method for diagnosing
      CDAD in faecal samples. It was also concluded that diagnosis of patients with
      diarrhoea who have been hospitalized for more than 72 h should focus mainly on
      the detection of C. difficile, irrespective of the physician's request.

PMID- 17172515
TI  - Evaluation of mannitol salt agar, CHROMagar Staph aureus and CHROMagar MRSA for
      detection of meticillin-resistant Staphylococcus aureus from nasal swab
      specimens.
AB  - Mannitol salt agar (MSA), CHROMagar Staph aureus (CSA) and CHROMagar MRSA (CSA
      MRSA) were evaluated with nasal surveillance specimens for their ability to
      detect Staphylococcus aureus and meticillin-resistant S. aureus (MRSA). CSA was
      found to be more sensitive than MSA in detecting S. aureus (98 versus 84.3 %;
      P=0.03). CSA and CSA-MRSA were equivalent in the ability to detect MRSA at 24 h
      (89.7 versus 87.2 %) and at 48 h (94.9 versus 94.9 %). When combined with
      Staphaurex slide confirmation testing, both CSA and CSA-MRSA were highly specific
      (100 %) media for detecting MRSA from nasal swab specimens.

PMID- 17172516
TI  - The use of local isolates in Western blots improves serological diagnosis of Lyme
      disease in Scotland.
AB  - Nine Scottish Borrelia burgdorferi isolates were investigated in IgG Western blot
      tests. Sera previously found to be positive and negative when tested by routine
      Western blots prepared from reference strain B. burgdorferi sensu stricto antigen
      had different outcomes with these isolates. Two isolates, E5 (Borrelia afzelii)
      and G4 (B. burgdorferi sensu stricto) performed well, reproducing Western blot
      positive results in 90 and 95% of tests, respectively. When antigens from both
      isolates were incorporated into a single IgG Western blot, the results of a panel
      of sera were improved when compared to the routine reference strain IgG Western
      blot. All of the sera positive by the routine Western blot remained positive
      using the Scottish isolate antigen mix. Twenty-three of the 25 negative sera
      remained negative and two produced an equivocal result. Of the 15 samples that
      tested IgG Western blot equivocal with the B. burgdorferi sensu stricto reference
      strain, 11 (73%) became weak or strong positive when tested with the B.
      afzelii/B. burgdorferi sensu stricto antigen mix (chi(2)=14.35, Yates'
      correction, P<0.001). In seven of these, a clinical picture of Lyme disease was
      consistent with the new results. The use of Scottish strains of B. afzelii and B.
      burgdorferi sensu stricto to provide antigen for the IgG Western blot improves
      the diagnosis of Lyme disease for patients in Scotland.

PMID- 17172517
TI  - Real-time TaqMan PCR for rapid detection and typing of genes encoding CTX-M
      extended-spectrum beta-lactamases.
AB  - The prevalence of CTX-M-producing members of the Enterobacteriaceae is increasing
      worldwide. A novel, multiplex, real-time TaqMan PCR assay to detect and type
      bla(CTX-M) genes is described which is an improvement on previously described
      techniques with respect to reduced assay time, elimination of the need for
      protracted post-PCR processing and the convenience of a single reaction vessel.
      Based on beta-lactam antibiogram and MIC data, 478 of 1279 Enterobacteriaceae
      isolates from clinical blood and urine culture specimens were selected and tested
      for extended-spectrum beta-lactamase (ESBL) production using phenotypic methods.
      The new TaqMan assay detected and typed bla(CTX-M) genes in 21 of 28 ESBL
      producing isolates.

PMID- 17172518
TI  - Rapid detection of Vibrio species using liquid microsphere arrays and real-time
      PCR targeting the ftsZ locus.
AB  - The development of rapid and sensitive molecular techniques for the detection of
      Vibrio species would be useful for the surveillance of sporadic infections and
      management of major outbreaks. Comparative sequence analysis of the ftsZ gene in
      the predominant Vibrio species that cause human disease revealed distinct alleles
      for each examined species, including Vibrio cholerae, Vibrio parahaemolyticus and
      Vibrio vulnificus. Light Upon eXtension (LUX) real-time PCR assays were developed
      to target these species-specific polymorphisms, and were successful in rapidly
      differentiating the major pathogenic Vibrio species. Luminex liquid microsphere
      array technology was used to develop a comprehensive assay capable of
      simultaneously detecting V. cholerae, V. parahaemolyticus and V. vulnificus.
      These assays permitted the identification of a presumptive V. parahaemolyticus
      isolate as Vibrio alginolyticus, which was verified using additional molecular
      characterization.

PMID- 17172519
TI  - Characterization of clinical isolates of Pseudomonas aeruginosa heterogeneously
      resistant to carbapenems.
AB  - Fourteen apparently carbapenem-susceptible Pseudomonas aeruginosa clinical
      isolates that exhibited colonies within the inhibition zone around carbapenem
      discs were analysed. MICs of carbapenems were determined and the isolates were
      genotyped by PFGE. Population analysis, one-step selection of carbapenem
      resistant mutants and growth curves of progenitors and carbapenem-resistant
      subpopulations were performed. Agar dilution MICs of imipenem and meropenem
      ranged from 0.5 to 4 mg l(-1) and from 0.25 to 2 mg l(-1), respectively.
      Population analysis confirmed subpopulations that grew in concentrations of up to
      18 mg l(-1) and 12 mg l(-1) of imipenem and meropenem, respectively, at
      frequencies ranging from 6.9 x 10(-5) to 1.1 x 10(-7), suggesting that they might
      not be detected by standard agar dilution MIC testing. The minority
      subpopulations exhibited MICs for imipenem ranging from 10 to 20 mg l(-1) and for
      meropenem from 4 to 14 mg l(-1). The one-step 8 mg l(-1) selection of imipenem
      resistant mutants test showed growth in all isolates at frequencies ranging from
      3.8 x 10(-4) to 5.1 x 10(-7). Growth curves revealed a prolonged lag phase and a
      short exponential phase for the heterogeneous subpopulations compared with their
      respective native subpopulations. These findings may be indicative that the use
      of carbapenems can lead to selection of P. aeruginosa resistant subpopulations
      that subsequently cause infections and result in treatment failure.

PMID- 17172520
TI  - In vitro activity of recombinant lysostaphin against Staphylococcus aureus
      isolates from hospitals in Beijing, China.
AB  - Lysostaphin is a glycylglycine endopeptidase. It cleaves the pentaglycine cross
      bridge structure unique to the staphylococcal cell wall and is considered to be a
      potential drug for Staphylococcus aureus. In the present study, the in vitro
      activity of recombinant lysostaphin was investigated in 257 S. aureus isolates
      collected from hospital patients in Beijing, China, by determination of MIC and
      minimum bactericidal concentration (MBC) and a time-kill curve test. An agar
      dilution method was used for MIC determination in all of the isolates and a
      macrobroth dilution method was employed to verify MIC values for a subset of the
      isolates. All of the S. aureus strains were sensitive to the recombinant
      lysostaphin with MICs ranging from 0.03 to 2 microg ml(-1) in the agar dilution
      assay. The antibacterial activity of lysostaphin was greater than that of
      vancomycin and other reference agents. For most of the isolates, the MICs from
      the agar dilution method were higher than those from the broth dilution method.
      The MBCs of lysostaphin in the test isolates were between 1- and 8-fold higher
      than their MIC values. Bactericidal activity (>99.9 % reduction) was observed
      after 2 h exposure of the isolates to lysostaphin at concentrations of > or =0.5
      MIC. Lysostaphin showed a rapid bactericidal activity against the test strains of
      meticillin-susceptible S. aureus and meticillin-resistant S. aureus. Its activity
      at > or =0.5 MIC was sustained for at least 6 h. These results will be
      informative for the clinical application and evaluation of lysostaphin.

PMID- 17172521
TI  - Polyclonality of Staphylococcus epidermidis residing on the healthy ocular
      surface.
AB  - Staphylococcus epidermidis is part of the normal bacterial flora on the ocular
      surface. The chromosomal DNA of bacterial isolates obtained from the conjunctival
      sac, upper and lower lid margins, and upper and lower Meibomian glands of healthy
      volunteers was subjected to SmaI digestion and PFGE to study the genetic
      diversity of the organisms. Multiple colonies were also examined of S.
      epidermidis derived from the conjunctival sac of the same subjects. Lastly,
      commensal bacteria were harvested from the ocular surfaces of four healthy
      subjects once a month for 6 months, and the genetic background of the S.
      epidermidis isolates was analysed. It was found that bacterial strains not only
      from different subjects but also from multiple ocular surface sites of the same
      subject exhibited different PFGE patterns. In five of 42 subjects multiple
      colonies of S. epidermidis were isolated from the conjunctival sac; three
      harboured multiple colonies with different PFGE patterns, and two manifested
      multiple colonies with identical PFGE patterns. S. epidermidis isolated from the
      conjunctival sac of the same subjects over a 6-month period exhibited varying
      PFGE patterns. The data demonstrate the polyclonality of S. epidermidis on the
      healthy ocular surface.

PMID- 17172522
TI  - Formation and properties of in vitro biofilms of ica-negative Staphylococcus
      epidermidis clinical isolates.
AB  - Coagulase-negative Staphylococcus epidermidis has become the leading cause of
      foreign-body infections due to its biofilm formation on all kinds of medical
      device surfaces. The biofilm development of S. epidermidis includes two steps:
      the initial attachment phase and the accumulative phase. In the accumulative
      phase, the polysaccharide intercellular adhesin (PIA), encoded by the icaADBC
      locus, is the major component mediating intercellular adhesion. However, recent
      studies have revealed the emergence of biofilm-positive/ica-negative
      staphylococcal clinical isolates. In this report, two ica-negative S. epidermidis
      clinical strains, SE1 and SE4, exhibited their heterogeneity in biofilm
      architecture under static and flow conditions, compared with the biofilm
      positive/ica-positive RP62A strain. Strains with this type of absence of PIA from
      biofilms also displayed intermediate resistance to vancomycin. More importantly,
      the cells of both SE1 and SE4 strains were more tolerant than those of RP62A to
      exposure to lysostaphin and vancomycin. Based on the results, it is suggested
      that the biofilm-positive/ica-negative strain represents a newly emergent
      subpopulation of S. epidermidis clinical strains, arising from selection by
      antibiotics in the nosocomial milieu, which displays a survival advantage in its
      host environment. Recent epidemiological data support this suggestion, by showing
      a tendency towards an increasing proportion of this subpopulation in
      staphylococci-associated infections.

PMID- 17172523
TI  - Evaluation of real-time PCR for the early detection of Legionella pneumophila DNA
      in serum samples.
AB  - Legionella pneumonia can be difficult to diagnose. Existing laboratory tests all
      have shortcomings, especially in the ability to diagnose Legionnaires' disease
      (LD) at an early stage of the disease in a specimen that is readily obtainable.
      The aim of this study was to assess the performance of PCR as a rapid diagnostic
      method and to compare the results of different PCR assays of serum samples from
      patients with LD. Samples included 151 serum samples from 68 patients with proven
      LD and 60 serum samples from 36 patients with respiratory tract infections other
      than Legionella. PCR assays were based on the 5S rRNA gene, 16S rRNA gene and the
      mip gene. The samples from patients with infections caused by pathogens other
      than Legionella all tested negative in PCR. Among the patients with proven LD
      54.4 % (37/68) tested positive in 5S rRNA PCR, 52.9 % (36/68) in mip gene PCR and
      30.9 % (21/68) in 16S rRNA PCR in the first available serum sample. The
      association between threshold cycle value in 5S PCR positive serum samples (n=49)
      and C-reactive protein value was determined, and showed a strong negative
      correlation (Pearson correlation coefficient r=-0.63, P<0.0001). In addition to
      existing tests for the diagnosis of LD, detection of Legionella DNA in serum
      could be a useful tool for early diagnosis of LD caused by any Legionella species
      and serogroup, and has the potential to provide a diagnosis in a time frame that
      could affect initial infection management.

PMID- 17172524
TI  - Amplified fragment length polymorphism of Streptococcus suis strains correlates
      with their profile of virulence-associated genes and clinical background.
AB  - Amplified fragment length polymorphism (AFLP) typing was applied to 116
      Streptococcus suis isolates with different clinical backgrounds
      (invasive/pneumonia/carrier/human) and with known profiles of virulence
      associated genes (cps1, -2, -7 and -9, as well as mrp, epf and sly). A dendrogram
      was generated that allowed identification of two clusters (A and C) with
      different subclusters (A1, A2, C1 and C2) and two heterogeneous groups of strains
      (B and D). For comparison, three strains from each AFLP subcluster and group were
      subjected to multilocus sequence typing (MLST) analysis. The closest relationship
      and lowest diversity were found for patterns clustering within AFLP subcluster
      A1, which corresponded with sequence type (ST) complex 1. Strains within
      subcluster A1 were mainly invasive cps1 and mrp+ epf+ (or epf*) sly+ cps2+
      strains of porcine or human origin. A new finding of this study was the
      clustering of invasive mrp* cps9 isolates within subcluster A2. MLST analysis
      suggested that A2 correlates with a single ST complex (ST87). In contrast to A1
      and A2, subclusters C1 and C2 contained mainly pneumonia isolates of genotype
      cps7 or cps2 and epf- sly-. In conclusion, this study demonstrates that AFLP
      allows identification of clusters of S. suis strains with clinical relevance.

PMID- 17172525
TI  - Phylogenetic analysis of bacterial and archaeal species in symptomatic and
      asymptomatic endodontic infections.
AB  - Phylogenetic analysis of bacterial and archaeal 16S rRNA was used to examine
      polymicrobial communities within infected root canals of 20 symptomatic and 14
      asymptomatic patients. Nucleotide sequences from approximately 750 clones
      amplified from each patient group with universal bacterial primers were matched
      to the Ribosomal Database Project II database. Phylotypes from 37 genera
      representing Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria and
      Proteobacteria were identified. Results were compared to those obtained with
      species-specific primers designed to detect Prevotella intermedia, Porphyromonas
      gingivalis, Porphyromonas endodontalis, Peptostreptococcus micros, Enterococcus
      sp., Streptococcus sp., Fusobacterium nucleatum, Tannerella forsythensis and
      Treponema denticola. Since members of the domain Archaea have been implicated in
      the severity of periodontal disease, and a recent report confirms that archaea
      are present in endodontic infections, 16S archaeal primers were also used to
      detect which patients carried these prokaryotes, to determine if their presence
      correlated with severity of the clinical symptoms. A Methanobrevibacter oralis
      like species was detected in one asymptomatic and one symptomatic patient. DNA
      from root canals of these two patients was further analysed using species
      specific primers to determine bacterial cohabitants. Trep. denticola was detected
      in the asymptomatic but not the symptomatic patient. Conversely, Porph.
      endodontalis was found in the symptomatic but not the asymptomatic patient. All
      other species except enterococci were detected with the species-specific primers
      in both patients. These results confirm the presence of archaea in root canals
      and provide additional insights into the polymicrobial communities in endodontic
      infections associated with clinical symptoms.

PMID- 17172526
TI  - Evaluation of different iron sources and their influence in biofilm formation by
      the dental pathogen Actinobacillus actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans, a pathogen associated with oral and extra
      oral infections, requires iron to grow under limiting conditions. Although
      incapable of producing siderophores, this pathogen could acquire iron by direct
      interaction with compounds such as haemin, haemoglobin, lactoferrin and
      transferrin. In this work the ability of different A. actinomycetemcomitans
      strains to bind and use different iron sources was tested. None of the strains
      tested used haemoglobin, lactoferrin or transferrin as sole sources of iron.
      However, all of them used FeCl(3) and haemin as iron sources under chelated
      conditions. Dot-blot binding assays showed that all strains bind lactoferrin,
      haemoglobin and haemin, but not transferrin. Insertion inactivation of hmsF,
      which encodes a predicted cell-envelope protein related to haemin-storage
      proteins produced by other pathogens, reduced haemin and Congo red binding
      drastically without affecting haemin utilization as an iron source under chelated
      conditions. Biofilm assays showed that all strains tested attached to and formed
      biofilms on plastic under iron-rich and iron-chelated conditions. However,
      scanning electron microscopy showed that smooth strains formed simpler biofilms
      than rough isolates. Furthermore, the incubation of rough cells in the presence
      of FeCl(3) or haemin resulted in the formation of more aggregates and
      microcolonies compared with the fewer cell aggregates formed when cells were
      grown in the presence of the synthetic iron chelator dipyridyl. These cell
      responses to changes in extracellular iron concentrations may reflect those that
      this pathogen expresses under the conditions it encounters in the human oral
      cavity.

PMID- 17172528
TI  - Bone marrow and skin granulomatosis in a patient with Bartonella infection.
AB  - This report describes a case of granulomatous inflammation, involving the bone
      marrow and skin, due to Bartonella infection in an immunocompetent patient. The
      clinical presentation included prolonged fever, pancytopenia, rash and hepatitis.
      Bartonella infection should thus be added to the growing list of entities that
      produce marrow granulomas and fever.

PMID- 17172529
TI  - Emergence of nalidixic acid-resistant Salmonella enterica serovar Typhi resistant
      to ciprofloxacin in India.

PMID- 17172527
TI  - Cerebral aspergillosis diagnosed by detection of Aspergillus flavus-specific DNA,
      galactomannan and (1-->3)-beta-D-glucan in clinical specimens.
AB  - A case of cerebral aspergillosis was diagnosed by the detection of Aspergillus
      flavus-specific DNA in brain biopsy and serum specimens. The diagnosis was also
      supported by detection of elevated levels of galactomannan and (1-->3)-beta-d
      glucan in serum specimens. Despite the presence of dichotomously branched septate
      hyphae in brain biopsy, the culture remained negative. The inability to isolate
      the organism in culture suggested that combined therapy of AmBisome and
      caspofungin was fungicidal for the fungus in the brain abscess.

PMID- 17172530
TI  - Rickettsia rickettsii infection causes apoptotic death of cultured cerebellar
      granule neurons.

PMID- 17172533
TI  - Current concepts in the diagnosis and management of vascular Ehlers-Danlos
      syndrome.

PMID- 17172531
TI  - Pharmacological effects of acute and repeated administration of Delta(9)
      tetrahydrocannabinol in adolescent and adult rats.
AB  - Adolescents of many mammalian species exhibit rapid physiological change that is
      accompanied by behaviors such as increased risk taking and social interaction
      with peers. Marijuana abusers frequently report that their initial use occurred
      during adolescence. Our goal was to determine whether the in vivo effects of
      Delta(9)-tetrahydrocannabinol (Delta(9)-THC) differed in adolescent and adult
      rats. Following initial testing with Delta(9)-THC in adolescent [postnatal day
      (PN)29] and adult (>PN60) rats of both sexes, we injected rats twice daily with
      10 mg/kg Delta(9)-THC or vehicle for 9.5 days. Subsequently, rats were again
      injected with their initial dose of Delta(9)-THC and tested. In all rats,
      Delta(9)-THC produced dose-dependent locomotor suppression, antinociception,
      hypothermia and catalepsy. Some age-dependent differences in potency and efficacy
      were noted. Although Delta(9)-THC dose-effect functions were more similar across
      age after repeated exposure, subchronic dosing produced greater change in the
      hypothermic and locomotor effects of Delta(9)-THC in adolescents, but less change
      in its antinociceptive effects. These results suggest that the effects of initial
      exposure to Delta(9)-THC may not be entirely predictive of the effects of
      repeated exposure. Despite similarities in pharmacological effects of Delta(9)
      THC after repeated use, adolescents and adults may exhibit differences in the
      pattern of transition from use to abuse.

PMID- 17172534
TI  - Commentary on "Current concepts in the diagnosis and management of vascular
      Ehlers-Danlos syndrome".

PMID- 17172535
TI  - Inferior mesenteric artery aneurysm combined with renal artery stenosis in a
      patient with neurofibromatosis.
AB  - A case is reported of an inferior mesenteric artery aneurysm that starts
      approximately 1 cm from its origin and ends at the proximal portion of the
      bifurcation of the sigmoidal and left colic arteries accompanied with complete
      absence of the celiac axis and superior mesenteric arteries. Additionally, left
      renal artery stenosis existed. The diagnosis was made by digital subtraction
      arteriography and confirmed by magnetic resonance arteriogram. Disease involving
      the inferior mesenteric artery is extremely uncommon. This may be the first
      reported case of neurofibromatosis in combination with renal artery stenosis and
      inferior mesenteric artery aneurysm associated with celiac and superior
      mesenteric artery occlusion and treated surgically.

PMID- 17172536
TI  - Commentary on "Inferior mesenteric artery aneurysm combined with renal artery
      stenosis in a patient with neurofibromatosis".

PMID- 17172537
TI  - Commentary on "Inferior mesenteric artery aneurysm combined with renal artery
      stenosis in a patient with neurofibromatosis".

PMID- 17172538
TI  - Neurofibromatosis type 1: from presentation and diagnosis to vascular and
      endovascular therapy.
AB  - Neurofibromatosis type 1, also called von Recklinghausen's disease, is an
      autosomal dominant disorder linked to chromosome 17, characterized by growth
      impairment of the neural crest cells (ectoderm) manifested by multiple neural
      tumors, cutaneous pigmentations, and Lisch nodules. Disease phenotype develops
      with time, making its penetrance almost complete by 5 years of age. Compression
      of the gastro-intestinal, urinary, or pulmonary tracts by visceral neurofibromas
      may generate serious complications. Neurofibromatosis type 1 is remarkable for
      its association with occlusive (stenoses) or aneurysmal arterial disease
      affecting predominantly the renal arteries and less often the abdominal aorta
      (middle aortic syndrome), and mesenteric and peripheral arteries. Appraisal of
      existing literature reveals that timely vascular intervention by way of
      conventional surgery and/or endovascular therapy may provide patients with
      effective and durable treatment. The far greater propensity for malignant
      connective/soft-tissue neoplasms and vascular disease in neurofibromatosis type
      1, amid potential complications from the gastro-intestinal, urinary, and
      pulmonary tracts, leads to a significantly increased morbidity and decreased life
      expectancy. Neurofibromatosis type 1, from presentation and diagnosis to its
      treatment, is reviewed, with emphasis on vascular disease and its management with
      open vascular surgery and endovascular therapy.

PMID- 17172539
TI  - Repair of abdominal aortic aneurysms: the benefits of offering both endovascular
      and open surgical techniques.
AB  - Two treatment options are available for abdominal aortic aneurysms (AAAs): open
      surgical technique with graft replacement and endovascular aortic aneurysm repair
      (EVAR) as a minimally invasive procedure. The intention of this review is to
      highlight the advantages of both procedures and to demonstrate that offering both
      procedures is beneficial for the patient when he or she makes the important
      decision regarding which treatment to select. A comparative evaluation of both
      treatment options is offered as well as a short description of the risk of
      rupture and its consequences. The authors discuss the latest literature as well
      as their own experiences. An innovative statistical approach-the propensity score
      based Cox model-is presented to evaluate the 2 treatment options. The benefits of
      offering both EVAR and open surgery permit optimal management of AAA for the
      individual patient and tailor the treatment to his or her organ dysfunctions and
      impaired physical status. In addition, EVAR offers a treatment option for
      otherwise incurable high-risk patients.

PMID- 17172540
TI  - The issue of spontaneous arteriovenous fistulae after superficial
      thrombophlebitis, endovenous ablations, and deep vein thrombosis: an unusual but
      predictable finding.
AB  - Spontaneous arteriovenous fistulae develop after the formation of venous thrombi
      in animals. In patients who have undergone endovenous ablation, angiogenesis
      occurs. This study was undertaken to examine the clinical presentation,
      development, and effects of spontaneous arteriovenous fistulae in patients with
      venous thrombosis.

PMID- 17172541
TI  - Commentary on "The issue of spontaneous arteriovenous fistulae after superficial
      thrombophlebitis, endovenous ablations, and deep vein thrombosis: an unusual but
      predictable finding".

PMID- 17172542
TI  - Commentary on "The issue of spontaneous arteriovenous fistulae after superficial
      thrombophlebitis, endovenous ablations, and deep vein thrombosis: an unusual but
      predictable finding".

PMID- 17172543
TI  - Hybrid endovascular and open surgical repair of a Crawford type III
      thoracoabdominal aneurysm in a high-risk patient.
AB  - Open thoracoabdominal aortic aneurysm repair carries a risk of significant
      morbidity and mortality. Thoracic endovascular aortic repair is an alternative,
      less invasive approach with lower morbidity and mortality but is not an option
      for thoracoabdominal aortic aneurysm because of visceral artery involvement. The
      authors describe the treatment of a 61-year-old high-risk male with an enlarging
      Crawford type III thoracoabdominal aneurysm using simultaneous aortic visceral
      debranching and thoracoabdominal endovascular aortic repair. A hybrid approach
      may be a safe alternative treatment option in high-risk surgical patients with
      thoracoabdominal aortic aneurysm.

PMID- 17172544
TI  - Commentary on "Hybrid endovascular and open surgical repair of a Crawford type
      III thoracoabdominal aneurysm in a high-risk patient".

PMID- 17172545
TI  - Subclavian-carotid transposition: an optimal approach through oblique neck
      incision.
AB  - Transposition of the subclavian artery into the common carotid artery has been
      used commonly to treat proximal subclavian occlusions. The number of
      transposition operations has recently increased as part of the debranching
      procedure associated with placement of a thoracic endograft. The major advantage
      is the avoidance of a prosthetic graft and the excellent long-term results.
      Traditionally, the operation has been performed through a transverse neck
      incision. This report describes the technique of transposition through an oblique
      neck incision made along the anterior border of the left sternocleidomastoid
      muscles. The surgeon stands on the opposite side of the table. The approach gives
      exposure of a long segment of the common carotid artery and an excellent view and
      exposure of the most proximal segment of the subclavian artery. Division of the
      sternocleidomastoid muscle is avoided.

PMID- 17172546
TI  - Commentary. The impact of shortened training times on the discipline of vascular
      surgery in the United Kingdom.

PMID- 17172547
TI  - The development of the Nucleus Freedom Cochlear implant system.
AB  - Cochlear Limited (Cochlear) released the fourth-generation cochlear implant
      system, Nucleus Freedom, in 2005. Freedom is based on 25 years of experience in
      cochlear implant research and development and incorporates advances in medicine,
      implantable materials, electronic technology, and sound coding. This article
      presents the development of Cochlear's implant systems, with an overview of the
      first 3 generations, and details of the Freedom system: the CI24RE receiver
      stimulator, the Contour Advance electrode, the modular Freedom processor, the
      available speech coding strategies, the input processing options of Smart Sound
      to improve the signal before coding as electrical signals, and the programming
      software. Preliminary results from multicenter studies with the Freedom system
      are reported, demonstrating better levels of performance compared with the
      previous systems. The final section presents the most recent implant reliability
      data, with the early findings at 18 months showing improved reliability of the
      Freedom implant compared with the earlier Nucleus 3 System. Also reported are
      some of the findings of Cochlear's collaborative research programs to improve
      recipient outcomes. Included are studies showing the benefits from bilateral
      implants, electroacoustic stimulation using an ipsilateral and/or contralateral
      hearing aid, advanced speech coding, and streamlined speech processor
      programming.

PMID- 17172548
TI  - MED-EL Cochlear implants: state of the art and a glimpse into the future.
AB  - Cochlear implantation is an accepted treatment method for adults and children
      with severe to profound hearing loss. Confidence in technology has led to changes
      in individuals who can receive a cochlear implant and changes in expected benefit
      with a cochlear implant. This article describes the research and development
      activities at MED-EL, which make possible the implementation of new speech-coding
      strategies as well as the application of acoustic and electric stimulation via a
      combined speech processor in MED-EL devices. Research on benefits from bilateral
      cochlear implantation and electric-acoustic stimulation are also reviewed.
      Finally, the potential of drug delivery systems is considered as a way to improve
      cochlear implant outcomes, and results from preliminary evaluations of a hybrid
      cochlear implant system with drug delivery capabilities are reported.

PMID- 17172549
TI  - Confounders in rehabilitation trials of task-oriented training: lessons from the
      designs of the EXCITE and SCILT multicenter trials.
AB  - Two multicenter randomized clinical trials (MRCT), the Extremity Constraint
      Induced Therapy Evaluation (EXCITE) to improve upper extremity function after
      stroke and the Spinal Cord Injury Locomotor Trial (SCILT) to enable functional
      walking after incomplete spinal cord injury, demonstrate that complex, task
      oriented physical therapies can be studied using a scientific methodology during
      inpatient or outpatient rehabilitation. In the past, a new therapy's benefit may
      have been overestimated by comparing it to no treatment or to a conventional
      treatment at a low intensity of practice. Sample sizes were often too small and
      may have failed to detect the efficacy of a new intervention. In addition,
      whereas statistical significance in outcomes has been critical to understanding
      whether one treatment is better than another, the clinical significance of
      outcomes must also impact the interpretation of the results of a trial. MRCT
      designs will continue to improve through attention to the limitations of
      preclinical animal models that offer a conceptual basis for the treatment,
      [corrected] from enrichment strategies at every phase of trial development,
      [corrected] from more vigorous dose-response studies using adaptive methods,
      [corrected] by capturing interim measures of behavior and functional
      neurophysiologic adaptations during the treatment phase, [corrected] by aiming
      for a clinically meaningful control intervention, [corrected] and by including
      ratio or interval outcome measures when feasible that capture a target of the
      intervention in relation to gains in daily functioning and quality of life.

PMID- 17172550
TI  - Constraint-induced movement therapy during early stroke rehabilitation.
AB  - BACKGROUND: Limited data are available about the effectiveness of early
      rehabilitation after stroke. OBJECTIVE: This is the 1st randomized controlled
      trial of constraint-induced movement therapy (CIMT) in subacute stroke to
      investigate neurophysiologic mechanisms and long-term outcome. METHODS: Within 2
      weeks after stroke, 23 patients with upper extremity (UE) weakness were
      randomized to 2 weeks of CIMT or traditional therapy at an equal frequency of up
      to 3 h/day. Motor function of the affected UE was blindly assessed before
      treatment, after treatment, and 3 months after stroke. Transcranial magnetic
      stimulation (TMS) measured the cortical area evoking movement of the affected
      hand. RESULTS: Long-term improvement in motor function of the affected UE did not
      differ significantly between patients who received CIMT versus intensive
      traditional therapy. All outcome comparisons showed trends favoring CIMT over
      intensive traditional therapy, but none was statistically significant except for
      improvements in the Fugl-Meyer (FM) UE motor scale immediately following
      treatment and in reported quality of hand function at 3 months. Improvement in UE
      motor function on the FM was associated with a greater number of sites on the
      affected cerebral hemisphere where responses of the affected hand were evoked by
      TMS. CONCLUSIONS: Future trials of CIMT during early stroke rehabilitation need
      greater statistical power, more inclusive eligibility criteria, and improved
      experimental control over treatment intensity. The relationship between changes
      in motor function and in evoked motor responses suggests that motor recovery
      during the 1st 3 months after stroke is associated with increased motor
      excitability of the affected cerebral hemisphere.

PMID- 17172551
TI  - The evolution of walking-related outcomes over the first 12 weeks of
      rehabilitation for incomplete traumatic spinal cord injury: the multicenter
      randomized Spinal Cord Injury Locomotor Trial.
AB  - BACKGROUND: The Spinal Cord Injury Locomotor Trial (SCILT) compared 12 weeks of
      step training with body weight support on a treadmill (BWSTT) that included
      overground practice to a defined but more conventional overground mobility
      intervention (CONT) in patients with incomplete traumatic SCI within 8 weeks of
      onset. No previous studies have reported walking-related outcomes during
      rehabilitation. METHODS: This single-blinded, randomized trial entered 107
      American Spinal Injury Association (ASIA) C and D patients and 38 ASIA B patients
      with lesions between C5 and L3 who were unable to walk on admission for
      rehabilitation. The Functional Independence Measure (FIM-L) for walking, 15-m
      walking speed, and lower extremity motor score (LEMS) were collected every 2
      weeks. RESULTS: No significant differences were found at entry and during the
      treatment phase (12-week mean FIM-L = 5, velocity = 0.8 m/s, LEMS = 35, distance
      walked in 6 min = 250 m). Combining the 2 arms, a FIM-L >or= 4 was achieved in <
      10% of ASIA B patients, 92% of ASIA C patients, and all of ASIA D patients.
      Walking speed of >or= 0.6 m/s correlated with a LEMS near 40 or higher.
      CONCLUSIONS: Few ASIA B and most ASIA C and D patients achieved functional
      walking ability by the end of 12 weeks of BWSTT and CONT, consistent with the
      primary outcome data at 6 months. Walking-related measures assessed at 2-week
      intervals reveal that time after SCI is an important variable for entering
      patients into a trial with mobility outcomes. By about 6 weeks after entry, most
      patients who will recover have improved their FIM-L to >3 and are improving in
      walking speed. Future trials may reduce the number needed to treat by entering
      patients with FIM-L < 4 at > 8 weeks after onset if still graded ASIA B and at >
      12 weeks if still ASIA C.

PMID- 17172552
TI  - Altered brain activation during cognitive control in patients with moderate to
      severe traumatic brain injury.
AB  - BACKGROUND: Persistent deficits in cognitive control have been documented
      following traumatic brain injury (TBI) but are inconsistently related to the
      presence and location of focal lesions. OBJECTIVE: Functional magnetic resonance
      imaging (fMRI) was used to examine brain activation during a cognitive control
      task in patients with moderate to severe TBI or orthopedic injury (OI). METHODS:
      Fourteen TBI patients and 10 OI patients underwent fMRI at 3 months postinjury
      using a stimulus-response compatibility task in which response accuracy and
      reaction time were measured. Performance between the groups was equated by
      individually adjusting the amount of training. Groups did not differ in age,
      gender, or education. RESULTS: Brain activation during stimulus-response
      incompatibility was greater in TBI patients than in OI patients within the
      cingulate, medial frontal, middle frontal, and superior frontal gyri. However,
      the positive regression of activation with response accuracy during stimulus
      response incompatibility indicated a stronger relationship for OI patients than
      the TBI group within the anterior cingulate gyrus, medial frontal, and parietal
      regions, as well as deep brain structures (eg, brainstem). The number of focal
      lesions within either the whole brain or within prefrontal areas was not related
      to brain activation, but there was a relationship between activation and TBI
      severity. CONCLUSIONS: These findings suggest that neural networks mediating
      cognitive control are altered after moderate to severe TBI, possibly as a result
      of diffuse axonal injury, and that the typical relationship of brain activation
      to performance is disrupted.

PMID- 17172553
TI  - Measurement error in functional balance and mobility tests for people with
      stroke: what are the sources of error and what is the best way to minimize error?
AB  - OBJECTIVE: To assess the degree and source of measurement error in functional
      balance and mobility tests for people with stroke, and to identify the most
      effective method of data collection to minimize error. DESIGN: To assess the
      degree and source of error, the total, systematic, and random error were
      calculated for within-session, test-retest, and interrater testing. To identify
      the most effective method of data collection, the total error was calculated for
      4 data collection methods: 1 familiarization trial, then scoring a 2nd trial; 2
      familiarization trials, then scoring a 3rd trial; averaging 2 trials, then
      averaging 3 trials. SETTING: Stroke services in National Health Service
      hospitals. PATIENTS: Thirty-five people with a poststroke hemiplegia.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Five tests provided interval-level
      data: arm raise (sitting and standing), weight shift, tap, and step-up. Four
      tests provided ratio-level data: forward reach (sitting and standing) and 5-m
      timed walk (with and without an aid). RESULTS: Total measurement error ranged
      from zero for the step-up test to 55% for within-session error for the 5-m walk
      without an aid. Ratio data tests showed somewhat greater error than interval data
      tests (5%-55% vs. 0%-46%). A within-session practice effect for the standing
      forward reach, 5-m walk (with and without an aid), and weight shift tests was
      found. For the other tests, random error was greater than the systematic error.
      Interrater testing had the least error. For most tests, the average of 2 trials
      produced the least measurement error. For the 5-m walk, the mean obtained from 2
      or 3 trials was equally effective. For the step-up test, the mean of 3 trials was
      slightly more effective. The overall error from all 3 sources was 3 lifts for
      sitting arm raise, 11 cm for sitting forward reach, 3 lifts for the standing arm
      raise, 7.5 cm for standing forward reach, 4.5 s for walking with an aid, 3 shifts
      on the weight shift test, 1.1 s for walking without an aid, 2 taps, and 1 step
      up. CONCLUSION: The tests using interval data showed less error than ratio-data
      tests and may be preferable measurement tools. Taking an average of 2 trials was
      the most accurate data collection method.

PMID- 17172554
TI  - Effects of a rostral motor cortex lesion on primary motor cortex hand
      representation topography in primates.
AB  - BACKGROUND: Small lesions to rostral versus caudal portions of the hand
      representation in the primary motor cortex (M1) produce different behavioral
      deficits. The goal of the present study was to determine if rehabilitative
      training has similar effects on functional topography of the spared M1 after
      rostral versus previously reported caudal M1 lesions. METHODS: Following a lesion
      to the rostral M1 hand area, monkeys were trained for 1 h/day for 30 days to
      retrieve food pellets from small wells using their impaired hand.
      Electrophysiological maps of the M1 were derived in anesthetized monkeys before
      infarct and after rehabilitative training using intracortical microstimulation.
      RESULTS: After a lesion to the rostral M1 and rehabilitative training, the size
      of the spared hand representation decreased 1.2%. This change is not
      statistically different from the 9% increase seen after caudal M1 lesion and
      rehabilitative training (P > 0.2). CONCLUSION: Postlesion training spares peri
      infarct hand area regardless of whether the lesion is in the rostral or caudal
      M1.

PMID- 17172555
TI  - Stroke affects the coordination of gaze and posture during preplanned turns while
      walking.
AB  - BACKGROUND: In healthy subjects, the act of walking and turning is accomplished
      by a sequential horizontal reorientation of gaze, head, and body toward the
      direction of the turn. Subjects with stroke, however, have difficulty altering
      their walking direction and present with loss of balance when performing a head
      turn or whole body rotation. OBJECTIVE: To study, in a pilot case study, the
      spatial and temporal coordination of gaze and posture during preplanned turns
      executed while walking in severely disabled and mildly disabled subjects with
      stroke as compared to a healthy control walking at slow speed. METHODS:
      Horizontal plane orientations of gaze, head, thorax, pelvis, and feet as well as
      the body's center of mass (CoM) trajectory were analyzed as subjects were walking
      straight or executing a 90-deg turn. RESULTS: Subjects with stroke revealed
      altered orientation and sequencing of gaze body segments. These alterations were
      more pronounced in the most severely disabled subject with stroke, especially
      when turning to the nonparetic side as compared to the paretic side. CONCLUSIONS:
      These findings suggest an altered coordination of gaze and posture during
      steering of locomotion in subjects with stroke. This altered coordination is
      likely due to a complex interaction of motor, sensory, and biomechanical factors
      that may explain the poor balance and poor control of heading direction during
      walking and turning in stroke.

PMID- 17172556
TI  - Integration of motor imagery and physical practice in group treatment applied to
      subjects with Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: The application of motor imagery practice in the
      treatment of Parkinson's disease (PD) is a novel treatment approach for improving
      motor function. The purpose of this study was to compare group treatment using a
      combination of physical and motor imagery practice with group treatment using
      only physical practice in subjects with PD. METHODS: Of 23 patients with
      idiopathic PD, 12 received combined therapy, whereas 11 received physical therapy
      alone. Exercises for both groups were applied during 1-h sessions held twice a
      week for 12 weeks. Comparable motor tasks provided to both groups included
      callisthenic exercises, functional tasks, and relaxation exercises. However, the
      experimental group was treated with both imagery and real practice, whereas the
      control group received only physical exercises. Outcome measures included the
      time required to complete sequences of movements, the performance of balance
      tasks, impairment and functional scores on the Unified Parkinson's Disease Rating
      Scale (UPDRS), and specific cognitive abilities (Stroop and clock drawing tests).
      RESULTS: Following the intervention, the combined treatment group exhibited
      significantly faster performance of movement sequences than the control group. In
      addition, the experimental subjects demonstrated higher gains in the mental and
      motor subsets of the UPDRS and in the cognitive tests. Both groups improved on
      the activities of daily living scale. CONCLUSIONS: The combination of motor
      imagery and real practice may be effective in the treatment of PD, especially for
      reducing bradykinesia. The implementation of this treatment regimen allows for
      the extension of practice time with negligible risk and low cost.

PMID- 17172557
TI  - The influence of treadmill inclination on the gait of ambulatory hemiparetic
      subjects.
AB  - INTRODUCTION: This study evaluated the influence of the degree of treadmill belt
      inclination for training of ambulatory patients with hemiparetic stroke. METHODS:
      Twelve patients were instructed to walk at 5 different levels of inclination (0%
      8%) while harness-secured on the treadmill. The gait velocity was kept constant
      during all conditions. Dependent variables were heart rate, gait cycle-dependent
      parameters, and electromyographic activation patterns of the weight-bearing
      muscles. RESULTS: Heart rate increased across all inclination levels, stride
      length increased and cadence decreased, whereas swing symmetry improved due to
      shortening of the relative swing phase of the affected side at the 6% and 8%
      inclination levels. No change in the activation pattern of the leg muscles was
      found. CONCLUSION: An inclination up to at least 8% can be accommodated for
      treadmill training by ambulatory stroke patients. For a given belt speed, heart
      rate increased without exceeding critical levels and patients walked with a more
      symmetric pattern. This protocol appeared to be safe in this selected group of
      subjects.

PMID- 17172558
TI  - Developing a Short Form of the Postural Assessment Scale for people with Stroke.
AB  - OBJECTIVE: To develop a Short Form of Postural Assessment Scale for Stroke
      patients (SFPASS) with sound psychometric properties (including reliability,
      validity, and responsiveness). METHODS: This study consisted of 2 parts:
      developing the SFPASS and cross-validation. In the 1st part, 287 people with
      stroke were evaluated with the PASS at 14- and 30-day post-stroke intervals. The
      authors reduced the number of test items that constitute the PASS by more than
      half (i.e., making 5-, 6-, and 7-item sets) and simplified the scoring system
      (i.e., collapsing the 4-level scale in the original PASS into a 3-level scale
      [PASS-3L]), making both 4-L and 3-L versions available. Thus, a total of 6
      SFPASSs were generated. In addition, 2 external criteria, the Barthel activities
      of daily living index and the Fugl-Meyer motor test, were used to examine the
      validity of the 6 SFPASSs. The psychometric properties of the new 6 SFPASSs were
      compared with each other as well as with those of the original PASS to determine
      which scale outperformed the others. In the 2nd part of the study, the authors
      cross-validated the best SFPASS using another independent sample of 179 people
      with stroke. RESULTS: All 6 SFPASSs demonstrated good reliability, validity, and
      responsiveness. However, the Bland-Altman plots showed that only the 5-item PASS
      3L demonstrated no systematic trend between the difference and mean score of the
      5-item PASS-3L and the original PASS. The 5-item PASS-3L also had psychometric
      properties similar to those of the original PASS, as demonstrated in a cross
      validation sample. CONCLUSION: The authors' results provide strong evidence that
      the 5-item PASS-3L has sound psycho-metric properties in people with stroke. The
      5-item PASS-3L is simple and fast to administer and is thus recommended.

PMID- 17172559
TI  - Functional Independence Measure for Children: a comparison of Chinese and
      Japanese children.
AB  - OBJECTIVE: The Functional Independence Measure for Children (WeeFIM) is a simple
      to-administer scale for assessing functional independence across 3 domains (self
      care, mobility, cognition) in children. There are normative data from America and
      Japan. In 2001 to 2002, the authors created a normative Chinese WeeFIM profile
      and compared this with the American one. In this study, they aimed to compare
      their Chinese normative data with the Japanese one. METHODS: A random sampling of
      445 normal Chinese children from different social classes in Hong Kong was
      conducted in the community. It was conducted via face-to-face interviews with the
      mother, and a normative database was created. RESULTS: Similar to the Japanese
      children, the WeeFIM total score and 3 main domain subscores (self-care,
      mobility, and cognition) increased progressively with age. In the self-care
      domain, Chinese children achieved modified independence or level 6 earlier in all
      items except toileting. For the mobility domain, the item chair transfer was
      achieved earlier in the Chinese children, whereas toilet transfer, stair, tub
      transfer, and locomotion were achieved later in Chinese children. As for
      cognition domain, the item problem solving was achieved earlier but
      comprehension, social interaction, and memory were achieved later in the Chinese
      children. The authors' results showed the same pattern of increasing WeeFIM score
      with increasing chronological age, which is similar to the Japanese children.
      There are 3 patterns of WeeFIM score achievement in this Chinese cohort. As for
      the Japanese children, the 3 patterns of WeeFIM score achievement from
      independent to dependent are 1) rapid change, 2) gradual change, and 3) linear
      change. CONCLUSIONS: WeeFIM is a validated standardized tool for assessing the
      outcome of rehabilitation programs. It should be widely used to assess
      rehabilitative achievement in children from different ethnic origins. The
      authors' previous study and this current study demonstrated that the authors'
      normative WeeFIM profile showed similar results to the American and Japanese
      children. However, there are minor differences in the WeeFIM scoring in the 3
      main domains, which might be due to cultural differences between ethnic groups.
      Thus, usage of the WeeFIM with a different age criteria in achieving independence
      according to local culture should be adopted.

PMID- 17172560
TI  - ApoE genotype affects allele-specific apo[a] levels for large apo[a] sizes in
      African Americans: the Harlem-Basset Study.
AB  - The genetic variability of apolipoprotein E (apoE) influences plasma lipoprotein
      levels, and allele frequencies differ between African Americans and Caucasians.
      As African Americans have higher lipoprotein [a] (Lp[a]) levels than Caucasians,
      we investigated the effects of the apoE gene on allele-specific apolipoprotein
      [a] (apo[a]) levels across ethnicity. We determined apo[a] sizes, allele-specific
      apo[a] levels (i.e., levels associated with alleles defined by size), and the
      apoE gene polymorphism in 231 African Americans and 336 Caucasians. African
      Americans, but not Caucasians, with the apo E2 genotype had lower levels of Lp[a]
      compared with those with the apo E4 genotype (9.6 vs. 11.2 nmol/l; P = 0.034,
      expressed as square root levels). Distribution of apo[a] alleles across apoE
      genotypes were similar between African Americans and Caucasians. Among African
      Americans with large apo[a], the allele-specific apo[a] level was significantly
      lower among epsilon2 carriers compared with epsilon3 or epsilon4 carriers (5.4
      vs. 6.6 and 7.4 nmol/l, respectively; P < 0.005, expressed as square root
      levels). In contrast, there was no significant difference in allele-specific
      apo[a] levels across apoE genotypes among Caucasians. For large apo[a] sizes,
      apoE genotype contributed to the observed African American-Caucasian differences
      in allele-specific apo[a] levels.

PMID- 17172562
TI  - Antipsychotics, cognitive decline and death in Alzheimer's disease: the London
      and South-East Region Alzheimer's Disease longitudinal study.

PMID- 17172563
TI  - Investigating the bias of space representations in patients with stroke.

PMID- 17172565
TI  - Neurological picture. Mid-brain molar tooth sign: expanding the clinical
      spectrum.

PMID- 17172564
TI  - Antithrombotic and interventional treatment options in cardioembolic transient
      ischaemic attack and ischaemic stroke.
AB  - Peer-reviewed data pertaining to anti-thrombotic and interventional therapy for
      transient ischaemic attack (TIA) or ischaemic stroke patients with non-valvular
      atrial fibrillation, atrial flutter, interatrial septal abnormalities, or left
      ventricular thrombus were reviewed. Long-term oral anticoagulant therapy with
      warfarin is the treatment of choice for secondary stroke prevention following TIA
      or minor ischaemic stroke in association with persistent or paroxysmal non
      valvular atrial fibrillation or atrial flutter. If warfarin is contraindicated,
      long-term aspirin is a safe, but much less effective alternative treatment option
      in this subgroup of patients with cerebrovascular disease. Management of young
      patients with TIA or stroke in association with an interatrial septal defect is
      controversial. Various treatment options are outlined, but readers are encouraged
      to include these patients in one of the ongoing randomised clinical trials in
      this area. It is reasonable to consider empirical anticoagulation in patients
      with TIA or ischaemic stroke in association with left ventricular thrombus
      formation following myocardial infarction or in association with idiopathic
      dilated cardiomyopathy. If warfarin is prescribed, one should aim for a target
      international normalised ratio of 2.5 (range 2-3) to achieve the best balance
      between adequate secondary prevention of cardioembolic events and the risk of
      major haemorrhagic complications.

PMID- 17172566
TI  - Neurological picture. A case of brain embolism during catheter embolisation of
      head arteriovenous malformation. What is the mechanism of stroke?

PMID- 17172569
TI  - Hughlings Jackson's early education.

PMID- 17172568
TI  - Paradoxical recovery in a bilingual patient with aphasia after right
      capsuloputaminal infarction.
AB  - We report the case of a bilingual dextral patient, who presented with an uncommon
      pattern of aphasic deficit following a right capsulo-putaminal infarction. In
      this patient, the linguistic deficit concerned the use of her mother tongue
      (Galician, L1) much more than the lesser practised second language (Spanish, L2).
      Our patient presented spontaneous fluent speech in L2 but not in L1, automatic
      translation into L2, and impaired repetition in L1, whereas comprehension was
      spared in both L1 and L2. Reading and writing were less valuable due to
      educational interference (reduced schooling). Spontaneous speech 16 months after
      the stroke showed the stability of the impairment. This is the first reporting of
      a crossed subcortical aphasia in a bilingual patient.

PMID- 17172567
TI  - PINK1 mutation heterozygosity and the risk of Parkinson's disease.
AB  - BACKGROUND: Mutations in the PTEN-induced kinase 1 (PINK1) gene have been
      identified in recessively inherited and sporadic early-onset parkinsonism (EOP).
      METHODS: A total of 131 Norwegian patients diagnosed with Parkinson's disease
      were included. Of them, 89 participants had EOP (onset < or = 50 years); the
      remaining had familial late-onset disease (mean age at onset 64 years). PINK1
      analysis included sequencing and gene dose assessment. Mutations were examined in
      350 controls. RESULTS: Heterozygous missense mutations in PINK1 were found in 3
      of 131 patients; none of the patients carried homozygous or compound heterozygous
      mutations. One of these three patients had a father affected by Parkinson's
      disease, and he carried the mutation. Three new and seven known polymorphic
      variants were identified, although none seemed to be associated with disease
      risk. CONCLUSIONS: PINK1 mutations are rare in Norwegian patients with EOP and
      familial Parkinson's disease. However, the data suggest that some heterozygous
      mutations might increase the risk of developing Parkinson's disease.

PMID- 17172570
TI  - Ablative thyroid treatment for thyrotoxicosis due to thyrotropin-producing
      pituitary tumours.
AB  - BACKGROUND: Thyrotropin (TSH)-secreting pituitary adenomas (TSHomas) are rare
      tumours that can be invasive. It has been suggested that thyroid surgery or
      radioiodine treatment should not be considered in patients with such tumours as
      these treatments may facilitate rapid and aggressive tumour expansion. AIM: To
      study the effects of thyroid ablative treatment on tumour size and thyroid status
      in two patients with TSHomas in whom the size of the adenoma was clearly
      documented before treatment was started. METHODS: Patients studied were: (1) a
      female patient with a TSHoma who declined to undergo pituitary surgery and
      underwent a total thyroidectomy instead and (2) a male patient who opted for
      radioiodine treatment for his recurrent TSHoma. Changes in tumour size on serial
      magnetic resonance imaging scans, and restoration of euthyroidism were studied.
      RESULTS: No marked changes in tumour size or features of aggressiveness occurred
      in these patients over periods of 8 and 12 years. Euthyroidism was restored and
      maintained in both patients. CONCLUSIONS: Ablative thyroid treatment can be a
      safe and successful option to treat TSHomas, but long-term and close follow-up of
      these patients is mandatory to ensure that the size and behaviour of the tumours
      do not change markedly.

PMID- 17172572
TI  - Vacuolar leucoencephalopathy and pulvinar sign in association with coeliac
      disease.

PMID- 17172571
TI  - Paroxysmal hemicrania responding to topiramate.
AB  - Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is
      classified along with cluster headache and short-lasting unilateral neuralgiform
      headache attacks with conjunctival injection and tearing (SUNCT) as a trigeminal
      autonomic cephalalgia. CPH is exquisitely responsive to indomethacin so much so
      that the response is one of the current diagnostic criteria. The case of a
      patient with CPH, who had marked epigastric symptoms with indomethacin treatment
      and responded well to topiramate 150 mg daily, is reported. Cessation of
      topiramate caused return of episodes, and the response has persisted for 2 years.
      Topiramate may be a treatment option in CPH.

PMID- 17172573
TI  - Mitochondrial disease mimicking Charcot-Marie Tooth disease.

PMID- 17172574
TI  - Isolated shoulder palsy due to cortical infarction: localisation and
      electrophysiological correlates of recovery.

PMID- 17172575
TI  - Rapid improvement of diffusion-weighted imaging abnormalities after glucose
      infusion in hypoglycaemic coma.

PMID- 17172576
TI  - Familial Creutzfeldt-Jakob disease with E200K mutation presenting with
      neurosensorial hypoacusis.

PMID- 17172577
TI  - Fugue associated with migraine.

PMID- 17172578
TI  - Severe chorea with positive anti-basal ganglia antibodies after
      herpesencephalitis.

PMID- 17172579
TI  - Brain stem encephalitis with central neurogenic hyperventilation.

PMID- 17172580
TI  - New formulation of Botox: complete antibody-induced treatment failure in cervical
      dystonia.

PMID- 17172582
TI  - Is Crohn's disease due to defective immunity?
AB  - The understanding of the pathophysiology of Crohn's disease is currently
      undergoing a reassessment. The concept of this disease as a primary T cell
      disorder is being questioned, with a new emphasis on the role of innate immunity
      in initiating early events and in perpetuating the inflammatory state. Crohn's
      disease has been proposed instead to result from impaired innate immunity,
      encompassing the mucosal barrier and cellular elements including neutrophils and
      macrophages. Recent advances in genetics, functional studies on innate immunity
      and therapeutic trials on patients with Crohn's disease have lent support to this
      evolving hypothesis.

PMID- 17172583
TI  - Inflammatory bowel disease: is it really just another break in the wall?

PMID- 17172584
TI  - vCJD and the gut: implications for endoscopy.

PMID- 17172585
TI  - An unusual cause of acute pancreatitis?

PMID- 17172587
TI  - Chronic diarrhoea with thickening of the colonic wall.

PMID- 17172586
TI  - Beta-glucosylceramide: a novel method for enhancement of natural killer T
      lymphoycte plasticity in murine models of immune-mediated disorders.
AB  - BACKGROUND: beta-Glucosylceramide, a naturally occurring glycolipid, exerts
      modulatory effects on natural killer T (NKT) lymphocytes. AIM: To determine
      whether beta-glucosylceramide can alter NKT function in opposite directions,
      colitis was induced by intracolonic installation of trinitrobenzenesulphonic
      acid, and hepatocellular carcinoma (HCC) was induced by transplantation of Hep3B
      cells. METHODS: The immunological effect of beta-glucosylceramide was assessed by
      analysis of intrahepatic and intrasplenic lymphocyte populations, serum cytokines
      and STAT protein expression. RESULTS: Administration of beta-glucosylceramide led
      to alleviation of colitis and to suppression of HCC, manifested by improved
      survival and decreased tumour volume. The beneficial effects were associated with
      an opposite immunological effect in the two models: the peripheral:intrahepatic
      CD4:CD8 lymphocyte ratio increased in the colitis model and decreased in the HCC
      group. The peripheral:intrahepatic NKT lymphocyte ratio decreased in beta
      glucosylceramide-treated mice solely in the HCC model. The effect of beta
      glucosylceramide was associated with decreased STAT1 and 4 expression, and with
      overexpression of STAT6, along with decreased interferon gamma levels in the
      colitis model, whereas an opposite effect was noted in the HCC model.
      CONCLUSIONS: beta-glucosylceramide alleviates immunologically incongruous
      disorders and may be associated with "fine tuning" of immune responses, by
      changes in plasticity of NKT lymphocytes.

PMID- 17172589
TI  - IBD5 is associated with an extensive complicated Crohn's disease feature:
      implications from genotype-phenotype analysis.

PMID- 17172590
TI  - Association of the macrophage migration inhibitory factor gene polymorphisms with
      inflammatory bowel disease.

PMID- 17172591
TI  - Molecular comparison of dominant microbiota associated with injured versus
      healthy mucosa in ulcerative colitis.

PMID- 17172588
TI  - Wound healing and fibrosis in intestinal disease.

PMID- 17172592
TI  - Deficiency for mannan-binding lectin is associated with antibodies to
      Saccharomyces cerevisiae in patients with Crohn's disease and their relatives.

PMID- 17172593
TI  - Heredity and DNA methylation in colorectal cancer.

PMID- 17172594
TI  - Limitations of non-ceruloplasmin-bound copper in routine clinical practice.

PMID- 17172595
TI  - Methylene blue but not indigo carmine causes DNA damage to colonocytes in vitro
      and in vivo at concentrations used in clinical chromoendoscopy.

PMID- 17172596
TI  - Menetrier's disease.

PMID- 17172597
TI  - Reduced splicing efficiency induced by synonymous substitutions may generate a
      substrate for natural selection of new splicing isoforms: the case of CFTR exon
      12.
AB  - Alternative splicing has been associated with increased evolutionary changes and
      with recent exon creation or loss. The addition of a new exon can be explained by
      its inclusion in only a fraction of the transcripts leaving the original form
      intact and giving to the new form the possibility to evolve independently but the
      exon loss phenomenon is less clear. To explore the mechanism that could be
      involved in CFTR exon 12 lower splicing efficiency in primates, we have analyzed
      the effect of multiple synonymous variations. Random patterns of synonymous
      variations were created in CFTR exon12 and the majority of them induced exon
      inclusion, suggesting a suboptimal splicing efficiency of the human gene. In
      addition, the effect of each single synonymous substitution on splicing is
      strongly dependent on the exonic context and does not correlate with available in
      silico exon splicing prediction programs. We propose that casual synonymous
      substitutions may lead to a reduced splicing efficiency that can result in a
      variable proportion of exon loss. If this phenomenon happens in in-frame exons
      and to an extent tolerated by the cells it can have an important evolutionary
      effect since it may generate a substrate for natural selection of new splicing
      isoforms.

PMID- 17172598
TI  - The thylakoid proton gradient promotes an advanced stage of signal peptide
      binding deep within the Tat pathway receptor complex.
AB  - Tat (twin arginine translocation) systems transport folded proteins across the
      thylakoid membrane of chloroplasts and the plasma membrane of most bacteria. Tat
      precursors are targeted by hydrophobic cleavable signal peptides with twin
      arginine (RR) motifs. Bacterial precursors possess an extended consensus,
      (S/T)RRXFLK, of which the two arginines and the phenylalanine are essential for
      efficient transport. Thylakoid Tat precursors possess twin arginines but lack the
      consensus phenylalanine. Here, we have characterized two stages of precursor
      binding to the thylakoid Tat signal peptide receptor, the 700-kDa cpTatC-Hcf106
      complex. The OE17 precursor tOE17 binds to the receptor by RR-dependant
      electrostatic interactions and partially dissociates during blue native gel
      electrophoresis. In addition, the signal peptide of thylakoid-bound tOE17 is
      highly exposed to the membrane surface, as judged by accessibility to factor Xa
      of cleavage sites engineered into signal peptide flanking regions. By contrast,
      tOE17 containing a consensus phenylalanine in place of Val(-20) (V - 20F) binds
      the receptor more strongly and is completely stable during blue native gel
      electrophoresis. Thylakoid bound V - 20F is also completely protected from factor
      Xa at the identical sites. This suggests that the signal peptide is buried deeply
      in the cpTatC-Hcf106 binding site. We further provide evidence that the proton
      gradient, which is required for translocation, induces a tighter interaction
      between tOE17 and the cpTat machinery, similar to that exhibited by V - 20F. This
      implies that translocation involves a very intimate association of the signal
      peptide with the receptor complex binding site.

PMID- 17172599
TI  - Impact of salt bridges on the equilibrium binding and adhesion of human CD2 and
      CD58.
AB  - This study describes quantitative investigations of the impact of single charge
      mutations on equilibrium binding, kinetics, and the adhesion strength of the CD2
      CD58 interaction. Previously steered molecular dynamics simulations guided the
      selection of the charge mutants investigated, which include the CD2 mutants D31A,
      K41A, K51A, and K91A. This set includes mutations in which the previous cell
      aggregation and binding data either agreed or disagreed with the steered
      molecular dynamics predictions. Surface plasmon resonance measurements quantified
      the solution binding properties. Adhesion was quantified with the surface force
      apparatus, which was used previously to study the closely related CD2-CD48
      interaction. The results reveal roles that these salt bridges play in equilibrium
      binding and adhesion. We discuss both the molecular basis of this behavior and
      its implications for cell adhesion.

PMID- 17172600
TI  - How to develop a business case for quality.
AB  - OBJECTIVE: To describe the steps in developing a business case for quality
      enhancing interventions (QEIs) in health care. ANALYSIS: The development of a
      business case for QEIs in health care involves 11 steps. These steps include (1)
      describing the intervention, (2) determining perspective, (3) identifying the
      effects of the intervention on quality, (4) designing the study, (5) identifying
      and measuring cash flows, (6) considering the effects of capacity constraints,
      (7) selecting a measure of return on investment, (8) determining the time horizon
      for the analysis, (9) determining the discount rate, (10) adjusting costs and
      savings for inflation, and (11) determining organizational readiness for business
      case development. A checklist offers guidance on assessing readiness for the
      business case. CONCLUSION: The absence of a 'business case' for quality is
      frequently cited as the reason health care organizations do not implement QEIs,
      despite decades of careful research demonstrating their effectiveness. Our
      continuing commitment to advancing the discipline of business case analysis is
      based on a belief that delineating the cost and economic implications of
      investments in QEIs is a critical threshold issue to widespread adoption of
      evidence-based quality improvements. We believe it is appropriate and timely to
      consider how best to standardize approaches and move the field of business case
      analysis forward.

PMID- 17172601
TI  - Long-term outcome after stroke: does dysphagia matter?
AB  - BACKGROUND: swallowing problems (dysphagia) are common following acute stroke and
      are independent predictors of short-term outcome. It is uncertain as to whether
      these swallowing problems are associated with outcome in the longer-term. AIM:
      insert to determine whether dysphagia present in the first week of acute stroke
      associated with long-term outcome. METHODS: a population-based long-term follow
      up of people with first in a life-time stroke. Dysphagia was assessed within 1
      week of stroke and patients were followed up at 3 months and yearly for 5 years
      by face-to-face interview. Outcome was defined by survival and place of
      residence, using multinomial logistic regression. Barthel Scores were divided
      into the two groups 15-20 and 0-14, and modelled using multiple logistic
      regression. RESULTS: there were 567 patients with dysphagia (mean age 74.3 years)
      and 621 with a safe swallow (mean age 69.6 years). Following multinomial logistic
      regression, residence in a nursing home was more likely to occur in those who
      failed the swallow test during the first week of their stroke; however, this only
      reached statistical significance at 3 months (relative risk ratio (RRR)=1.73; 95%
      confidence interval (CI) 1.02 to 2.95), and years 4 (RRR 3.35, 1.37-8.19) and 5
      (RRR 3.06, 1.06-8.83). There was also a significant association with increased
      mortality only during the first three months (RRR 2.03, 1.12 to 3.67).
      CONCLUSION: this study confirms that the presence of dysphagia during the acute
      phase of stroke is associated with poor outcome during the subsequent year,
      particularly at 3 months, and is associated with increased institutionalisation
      rate in the long term.

PMID- 17172602
TI  - The penitentiary visit--a new role for geriatricians?
AB  - The number of older prisoners is increasing and, with reforms in the prison
      health service, there is a requirement to provide equity of access to standard
      healthcare services. The health of older prisoners is often poor, with high
      levels of psychiatric and physical illnesses, compounded by poor access to
      appropriate rehabilitation and resettlement services. A recent case presenting to
      our department highlighted these deficits and illustrated how inputs from a
      geriatrician could be useful to older prisoners (see Appendix 1, available at
      www.ageing.oxfordjournals.org). We propose that regular penitentiary visits may
      be an important new role for geriatricians at a supra-regional level.

PMID- 17172603
TI  - How might a crisis in long-term care of people with dementia be averted.

PMID- 17172604
TI  - Determinants of outcome in anticoagulation-associated cerebral hematoma requiring
      emergency evacuation.
AB  - OBJECTIVE: To analyze the likelihood of recovery and prognostic factors in
      patients with massive anticoagulation-associated intracerebral hemorrhage treated
      with surgical evacuation after reversal of anticoagulation. DESIGN: Retrospective
      case series. SETTING: Neurological-Neurosurgical Intensive Care Unit at Mayo
      Clinic. Patients Seventeen consecutive patients with large anticoagulation
      associated intracerebral hemorrhage. Intervention Surgical evacuation of
      intracerebral hemorrhage. Main Outcome Measure Functional outcome was assessed
      using the modified Rankin scale. RESULTS: Before surgery, all patients had
      pronounced (>1-cm) shift of the septum pellucidum and one third had clinical
      signs of uncal herniation. Still, favorable outcome (modified Rankin scale score
      < or =3) was achieved by 11 patients (65%). All patients with good recovery awoke
      within 36 hours of surgery. Older age (P = .05) and serious systemic
      complications after surgery (P<.01) were significantly associated with lack of
      neurological recovery and fatal outcome. CONCLUSIONS: Emergency surgery for
      select deteriorating patients with large anticoagulation-associated intracerebral
      hemorrhage is compatible with favorable outcome despite the presence of clinical
      and radiological signs of herniation before the evacuation.

PMID- 17172605
TI  - Pedaling from genotype to phenotype.

PMID- 17172606
TI  - Neuroprotection in the peripheral nervous system: rationale for more effective
      therapies.
AB  - Most peripheral neuropathies are length dependent and result in distal axonal
      degeneration rather than loss of neuronal cell bodies. Available therapies for
      axonal peripheral neuropathies are designed to control painful symptoms and not
      to treat the underlying axonal degeneration. Many neuroprotective therapies are
      being developed, primarily for central nervous system disorders such as stroke or
      multiple sclerosis. However, strategies with the purpose of promoting survival of
      injured neurons (ie, preventing cell death) may not be applicable in many
      peripheral nervous system illnesses when the primary pathologic disorder that
      leads to symptoms is distal axonal degeneration. Neuronal cell death, if it
      occurs, is often a late event and may be untreatable in the near future. In
      contrast, distal axonal degeneration is an early event that may be amenable to
      treatment. Mechanistic studies that examine the axon-glia interaction and axonal
      biology are likely to yield novel therapeutic targets for peripheral
      neuropathies.

PMID- 17172607
TI  - Clinical and demographic predictors of long-term disability in patients with
      relapsing-remitting multiple sclerosis: a systematic review.
AB  - OBJECTIVE: To identify clinical and demographic factors associated with long-term
      disability in patients with relapsing-remitting multiple sclerosis. DATA SOURCES:
      We searched the MEDLINE (1966-May 2005), EMBASE, CINAHL, Cochrane, and PsycINFO
      computerized databases, and reviewed reference lists of retrieved articles. STUDY
      SELECTION: We included studies that examined predictors of long-term disability
      in patients with relapsing-remitting multiple sclerosis. We excluded studies that
      did not distinguish relapsing-remitting multiple sclerosis from primary
      progressive multiple sclerosis, enrolled fewer than 40 subjects, observed
      subjects for less than 5 years, or collected follow-up information in less than
      80% of the inception cohort. DATA EXTRACTION: Two reviewers assessed study
      quality in 4 domains: cohort assembly, definitions and assessments of prognostic
      factors and outcomes, and statistical methods. One reviewer extracted data on the
      direction, magnitude, precision, and statistical significance of the effect of
      each predictor on prognosis. DATA SYNTHESIS: Heterogeneity of study designs
      precluded us from pooling the results of 27 eligible studies. Study quality was
      limited by cross-sectional design, enrollment of prevalent cases from referral
      centers, and lack of multivariate adjustment. Sphincter symptoms at onset (hazard
      ratio, 1.1-3.1), incomplete recovery from the first attack (hazard ratio, 1.3
      3.3), and a short interval between the first and second attack (hazard ratio, 1.6
      1.9) were most strongly and consistently associated with poor prognosis. Other
      factors widely believed to be of prognostic importance, including sex and age at
      onset, demonstrated inconsistent or weak effects on prognosis. CONCLUSIONS: The
      most robust predictors of long-term physical disability in relapsing-remitting
      multiple sclerosis are sphincter symptoms at onset and early disease course
      outcomes. These factors can be used to guide treatment decisions for drugs with
      significant toxicities.

PMID- 17172608
TI  - Potential applications and limitations of proteomics in the study of neurological
      disease.

PMID- 17172609
TI  - Muscle phenotype and mutation load in 51 persons with the 3243A>G mitochondrial
      DNA mutation.
AB  - BACKGROUND: Mitochondrial disorders are generally not associated with a clear
      phenotype-genotype relationship, which complicates the understanding of the
      disease and genetic counseling. OBJECTIVE: To investigate the relationship
      between the muscle and blood mitochondrial DNA mutation load and phenotype.
      DESIGN: Survey. SETTING: The Neuromuscular Research Unit, Rigshospitalet,
      Copenhagen, Denmark. PARTICIPANTS: Fifty-one persons with the 3243A>G point
      mutation of mitochondrial DNA, and 20 healthy control subjects. METHODS: We
      recorded the maximal oxygen uptake (Vo(2)max), maximal workload, resting and peak
      exercise plasma lactate levels, muscle and blood mutation load, muscle
      morphology, and presence of diabetes mellitus and hearing impairment in all
      subjects. RESULTS: Muscle mutation load (mean +/- SE, 50% +/- 5%; range, 2%-95%)
      correlated with Vo(2)max and resting plasma lactate level (P<.001; R>/=0.64). All
      persons except 5 with a muscle mutation load above 50% had abnormal Vo(2)max and
      morphology on muscle biopsy findings. Persons with hearing impairment and
      diabetes mellitus had a muscle mutation load above 65%. The mutation load in
      blood (mean +/- SE, 18% +/- 3%; range, 0%-61%) did not correlate with Vo(2)max,
      resting plasma lactate levels, or presence of hearing impairment or diabetes
      mellitus. CONCLUSIONS: This study demonstrates a close relationship between the
      muscle mutation load and phenotype in persons carrying the 3243A>G mutation. The
      lack of correlation between the mutation load in blood and symptoms from other
      tissues emphasizes the importance of assessing phenotype-genotype correlations in
      the same tissue in mitochondrial disease. The results indicate that the threshold
      of muscle mutation load at which oxidative impairment occurs can be as low as
      50%, which is as much as 40% lower than that suggested by in vitro studies.

PMID- 17172610
TI  - A positron emission tomography study on the role of nigral lesions in
      parkinsonism in patients with amyotrophic lateral sclerosis.
AB  - BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) sometimes exhibit
      parkinsonism, but the lesion responsible for parkinsonism has not been
      extensively studied. OBJECTIVE: To test whether nigrostriatal system dysfunction
      is responsible for parkinsonism in ALS. DESIGN: From the 182 ALS patients who
      were admitted to our neurology ward during the past 10 years, we extracted all
      the patients who satisfied the criteria of both parkinsonism and ALS. SETTING:
      The University of Tokyo Hospital. METHODS: We conducted [(18)F]L-dopa and
      [(11)C]N-methylspiperone positron emission tomography and technetium Tc 99m
      hexamethylpropyleneamine oxime single-photon emission computed tomography studies
      on 5 patients with ALS manifesting overt parkinsonism. RESULTS: Two male and 3
      female patients (average age, 63.2 +/- 5.8 years) had ALS for an average of 28.6
      +/- 21.5 months and had parkinsonism for an average of 15.2 +/- 11.4 months.
      Features of their parkinsonism were characterized by outstanding bradykinesia
      without resting tremor or dementia. The results of positron emission tomography
      studies indicated normal nigrostriatal function, but those of single-photon
      emission computed tomography demonstrated decreased blood flow in the
      frontotemporal cortices. CONCLUSION: It is likely that parkinsonism in ALS is due
      to cortical lesions rather than nigrostriatal dysfunction and that both symptoms
      are the clinical manifestation of frontotemporal dementia with motor neuron
      diseases, including classic ALS.

PMID- 17172611
TI  - Inverse relationship between brain noradrenaline level and dopamine loss in
      Parkinson disease: a possible neuroprotective role for noradrenaline.
AB  - BACKGROUND: Experimental findings using animal models of Parkinson disease (PD)
      suggest that noradrenaline might protect dopamine neurons from damage. OBJECTIVE:
      To assess whether human brain regions having high levels of noradrenaline are
      less susceptible to dopamine loss in PD. DESIGN: Case-control study. SETTING:
      Postmortem investigation. PARTICIPANTS: Autopsied brains of patients with PD and
      of healthy control subjects. Main Outcomes Measures We compared the extent of
      dopamine loss in different regions relative to levels of noradrenaline found in
      healthy brain, with special attention devoted to the dopamine-rich nucleus
      accumbens, which has noradrenaline-rich and noradrenaline-poor subdivisions.
      RESULTS: Among 20 brain areas, dopamine loss in PD was negatively correlated with
      healthy noradrenaline levels (r = 0.83), with regions rich in noradrenaline (eg,
      the noradrenaline-rich portion of the nucleus accumbens) spared from dopamine
      loss. However, within the striatum, noradrenaline levels in the caudate and
      putamen were similar, despite dopamine's being more markedly reduced in the
      putamen. CONCLUSIONS: Our postmortem data are consistent with animal findings
      suggesting that noradrenaline might affect dopamine neuron loss in PD and that a
      noradrenergic approach (although not aimed at the as yet unknown primary cause of
      PD) could be neuroprotective. This possibility should also be considered when
      noradrenergic therapy is provided for symptomatic purposes in PD.

PMID- 17172612
TI  - Silent ischemic lesion recurrence on magnetic resonance imaging predicts
      subsequent clinical vascular events.
AB  - BACKGROUND: Previous studies identified a high frequency of silent ischemic
      lesion recurrence on magnetic resonance imaging (MRI) after an index stroke.
      OBJECTIVE: To investigate whether ischemic lesion recurrence on MRI predicts
      subsequent clinical events. DESIGN: Retrospective cohort study. SETTING: General
      community hospital. Patients We recruited 120 patients who experienced an acute
      ischemic stroke (IS) and who underwent initial MRI within 24 hours of onset and
      subsequent MRI on day 5. Of those patients, 68 underwent follow-up MRI up to 90
      days after onset. MAIN OUTCOME MEASURES: Early silent lesion recurrence was
      defined as new asymptomatic ischemic lesions on 5-day MRI, and late silent lesion
      recurrence was defined as those on 30- or 90-day MRI. Patients were followed up
      for recurrent vascular events by interviews. RESULTS: Among the 104 patients
      (86.7%) who had available clinical outcome data, 35 (33.7%) had early silent
      lesion recurrence; 15 (22.1%) of 68 patients had late silent lesion recurrence.
      Of the patients, 8 experienced a recurrent IS, 3 experienced a transient ischemic
      attack, and 3 had vascular deaths during a mean +/- SD follow-up of 19.3 +/- 9.0
      months. For recurrent IS as a clinical end point, late silent lesion recurrence
      independently predicted recurrent IS (odds ratio, 6.55; 95% confidence interval,
      1.09-39.55) by the Cox proportional hazards model. For combined clinical end
      points, early (odds ratio, 3.19; 95% confidence interval, 1.02-10.00) and late
      (odds ratio, 8.09; 95% confidence interval, 1.29-50.91) silent lesion recurrences
      independently predicted clinical recurrent IS, transient ischemic attack, or
      vascular deaths. CONCLUSION: These data suggest that silent ischemic lesion
      recurrence on MRI may be a potential surrogate marker of clinical recurrence.

PMID- 17172613
TI  - Comparison of spontaneous intracranial vertebral artery dissection with large
      artery disease.
AB  - OBJECTIVE: To compare clinical and angiographic characteristics and stroke
      patterns between spontaneous intracranial vertebral artery dissection (VAD) and
      vertebral large artery disease (LAD) (atherosclerosis). DESIGN: Retrospective
      study. SETTING: Tertiary referral center for cerebrovascular diseases. Patients
      Twenty-two patients with spontaneous VAD and 25 with LAD in the intracranial
      portion of the vertebral artery. MAIN OUTCOME MEASURES: We compared (1) clinical
      characteristics, including epidemiologic data, vascular risk factors including
      inflammatory markers, the presence of headache, and stroke syndromes and
      severity; (2) stroke pattern on diffusion-weighted imaging, which was classified
      as vertebral perforator infarct, basilar perforator infarct, small scattered
      infarct, large scattered infarct, and territorial infarct; and (3) angiographic
      findings, ie, the distribution of involved arteries, degree of stenosis, and the
      involvement on the anterior circulation and calcification of vertebral artery.
      RESULTS: Although patients with VAD were younger, and more often had headaches
      and fewer vascular risk factors than those with LAD (P<.01 in all cases), these
      clinical features were also observed in some LAD patients. Diffusion-weighted
      imaging data showed that vertebral perforator infarct and small scattered infarct
      were most common in the VAD group, while territorial infarct and large scattered
      infarct were most common in the LAD group (P = .02). On angiography, LAD more
      frequently had anterior circulation arterial involvement (P = .002), higher
      degree of stenosis (P = .002), and calcifications (P = .008). CONCLUSION: Our
      findings indicate that results of diffusion-weighted imaging and noninvasive
      vascular studies might provide clues to the clinical characteristics in
      differential diagnosis between VAD and LAD.

PMID- 17172614
TI  - Clinical implications of status epilepticus in patients with neoplasms.
AB  - OBJECTIVES: To elucidate factors that contribute to the development of status
      epilepticus (SE) and determine prognostic factors and the impact on 30-day
      survival. DESIGN: Retrospective review of medical records. SETTING: University of
      Virginia Health System. Patients Thirty-five patients with SE secondary to a
      tumor, either primary or systemic, or its treatment. MAIN OUTCOME MEASURES:
      Seizure control, 30-day mortality, and overall survival. RESULTS: Status
      epilepticus most commonly occurred at tumor presentation or progression and was
      controlled in all cases. Thirty-day mortality was 23%. Patients with systemic
      cancer were at higher risk of death, although they were older and had more acute
      comorbidities. Age, tumor type, status of tumor at time of event, history of
      epilepsy, and status type were not predictive of mortality. Age was associated
      with a higher rate of nursing home placement and shorter overall survival.
      Overall survival was determined by underlying tumor. CONCLUSIONS: Status
      epilepticus in patients with cancer is responsive to therapy. Workup of
      underlying causes is indicated, even in the presence of subtherapeutic
      antiepileptic drug levels, because coexistent conditions contributing to the
      development of SE may be present. In those with known cancer, brain imaging
      should be performed because SE usually occurs in the setting of tumor progression
      or new metastases.

PMID- 17172615
TI  - Frequency and predictors of nonconvulsive seizures during continuous
      electroencephalographic monitoring in critically ill children.
AB  - OBJECTIVE: To determine the incidence, predictors, and timing of nonconvulsive
      seizures (NCSz) during continuous electroencephalographic monitoring (cEEG) in
      critically ill children. METHODS: We identified critically ill children who
      underwent cEEG during a 4-year period. Multivariate logistic regression analysis
      was performed to determine variables associated with NCSz. RESULTS: Among 117
      monitored children, 44% had seizures on cEEG and 39% had NCSz. The majority of
      patients with seizures (75%) had purely NCSz, and 23% of patients had status
      epilepticus, which was purely nonconvulsive in 89% of cases. Seizures occurred
      immediately on cEEG initiation in 15%, within 1 hour in 50%, and within 24 hours
      in 80%. Those with clinical seizures prior to cEEG were more likely to have NCSz
      on cEEG (83%) than those without prior seizures (17%). On multivariate analysis,
      NCSz were associated with periodic lateralized epileptiform discharges and
      absence of background reactivity. CONCLUSIONS: Seizures, the majority being NCSz,
      are common during cEEG in critically ill children (seen in 44% of patients). Half
      are detected in the first hour of recording, whereas 20% are not detected until
      after more than 24 hours of recording. Nonconvulsive seizures are associated with
      periodic lateralized epileptiform discharges and absence of reactivity on cEEG.
      This study confirms the importance of prolonged cEEG for critically ill children
      as a means to detect NCSz.

PMID- 17172616
TI  - Factors associated with the development of motor fluctuations and dyskinesias in
      Parkinson disease.
AB  - BACKGROUND: Motor fluctuations and dyskinesias can cause disability and reduce
      quality of life for patients with Parkinson disease (PD). OBJECTIVES: To evaluate
      factors associated with the development of motor fluctuations and dyskinesias and
      to assess the sequence in which they occur in individual patients. DESIGN: We
      performed a retrospective analysis of data from a randomized clinical trial
      comparing pramipexole dihydrochloride and levodopa as initial treatment for PD.
      Subjects were followed up for 48 to 58 months and evaluated at 3-month intervals
      for the presence of motor fluctuations and dyskinesias. SETTING: Academic and
      private practices. Patients Three hundred one patients with early Parkinson
      disease were enrolled in this study between October 2, 1996, and August 21, 1997,
      and were observed through August 24, 2001, when the last patient enrolled
      completed 4 years of follow-up. MAIN OUTCOME MEASURES: Order of appearance of
      motor fluctuations and dyskinesias, time to the first occurrence of motor
      fluctuations, and time to the first occurrence of dyskinesias. RESULTS: One
      hundred eighty-nine subjects (62.8%) developed motor complications. Of these, 71
      (37.6%) developed fluctuations but not dyskinesias, 23 (12.2%) developed
      dyskinesias but not fluctuations, 48 (25.4%) developed fluctuations before
      dyskinesias, 33 (17.5%) developed dyskinesias before fluctuations, and 14 (7.4%)
      developed both at the same time. Factors significantly associated with earlier
      occurrence of dyskinesia were Hoehn and Yahr stage of 2 or higher, cumulative
      levodopa dose, cumulative levodopa equivalent dose (levodopa plus pramipexole),
      and occurrence of motor fluctuations. Pramipexole treatment was associated with
      later occurrence of dyskinesias. Factors associated with earlier occurrence of
      motor fluctuations were cumulative levodopa dose, cumulative levodopa equivalent
      dose, and occurrence of dyskinesias. Factors associated with later occurrence of
      motor fluctuations were age at onset of 65 years or older and pramipexole
      treatment. CONCLUSIONS: Higher cumulative levodopa doses and higher cumulative
      levodopa equivalent doses (levodopa plus pramipexole) were associated with the
      earlier occurrence of motor complications. Motor fluctuations and dyskinesias
      appear to be interrelated because the presence of one is associated with the
      earlier development of the other.

PMID- 17172617
TI  - Motor dysfunction in mild cognitive impairment and the risk of incident Alzheimer
      disease.
AB  - BACKGROUND: Little is known about motor function in mild cognitive impairment
      (MCI) and its relation to the risk of Alzheimer disease (AD). OBJECTIVE: To
      examine motor function in persons with MCI and its relation to risk of AD.
      DESIGN: Longitudinal cohort study. SETTING: More than 40 Catholic religious
      orders across the United States. PARTICIPANTS: We studied 816 older Catholic
      clergy members from the Religious Orders Study. At the baseline evaluation, they
      were classified as having no cognitive impairment (n = 558), MCI (n = 198), or
      dementia (n = 60). MAIN OUTCOME MEASURES: Motor function was assessed at baseline
      using performance-based measures of upper and lower extremity function and a
      modified version of the motor section of the Unified Parkinson's Disease Rating
      Scale, from which previously established measures of parkinsonian signs were
      derived. Clinical evaluations for dementia and AD were repeated annually for up
      to 10 years. All analyses controlled for age, sex, educational level, and
      possession of at least 1 apolipoprotein E epsilon4 allele. RESULTS: At baseline,
      individuals with MCI had impaired motor function relative to those without
      cognitive impairment and superior motor function vs those with dementia. Among
      those with MCI, baseline levels of lower extremity motor performance,
      parkinsonian gait, and bradykinesia were inversely related to risk of AD, even
      after controlling for clinical stroke. Thus, a person with impaired lower limb
      performance or parkinsonian gait (10th percentile) was 2 to 3 times more likely
      to develop AD than a person with good lower limb function (90th percentile).
      CONCLUSIONS: Persons with MCI also have impaired motor function, and the degree
      of impairment in lower extremity function is related to the risk of AD.

PMID- 17172618
TI  - Pathologic and nicotinic receptor binding differences between mild cognitive
      impairment, Alzheimer disease, and normal aging.
AB  - BACKGROUND: Neurochemical and pathologic studies show that mild cognitive
      impairment (MCI) is frequently a transitional state between normal aging and
      Alzheimer disease (AD). Neuropathologic sample sizes have been limited because
      relatively few individuals with MCI die before dementia develops. Decreased
      neocortical nicotinic receptor binding is characteristic of AD but has not been
      investigated in subjects with MCI. OBJECTIVE: To assess nicotinic receptor
      binding and pathologic differences in control subjects with no dementia (ND) and
      in subjects with clinically and pathologically described MCI or Alzheimer
      disease. DESIGN: This was a clinicopathologic analysis. Subjects with ND had no
      demonstrable cognitive or functional impairment. Subjects with MCI met Petersen
      clinical criteria for single- or multiple-domain amnestic MCI and died before the
      disorder progressed to AD. Subjects with AD met National Institute for
      Neurological Diseases and Stroke/Alzheimer's Disease and Related Disorders
      Association clinical criteria for AD. All subjects underwent a complete
      diagnostic and semiquantitative neuropathologic examination. Data were examined
      after both clinical and histopathologic classification of subjects. SETTING: Sun
      Health Research Institute Brain Donation Program, and Arizona Alzheimer Disease
      Center. PARTICIPANTS: Twenty-one control subjects with ND, 8 subjects with MCI,
      and 70 subjects with AD, prospectively followed up to autopsy. MAIN OUTCOME
      MEASURES: Nicotinic acetylcholine receptor binding value, total tangle density,
      total plaque density, and Braak stage. RESULTS: At the last examination before
      death, subjects with AD were significantly younger, less educated, and more
      cognitively and globally impaired compared with subjects with ND. When
      categorized by clinical diagnosis, MCI was always intermediate between ND and AD.
      On the whole, MCI was pathologically intermediate between ND and AD for senile
      plaque density, neurofibrillary tangle density, and Braak stage, but some
      subjects with MCI lacked neuritic plaques entirely. Binding for nicotinic
      acetylcholine receptors did not differ between the ND and MCI groups, but it was
      significantly less in the AD group. CONCLUSIONS: Most MCI may be considered a
      transitional state between ND and AD clinically and neuropathologically, but in
      some MCI cases there is lack of neuritic plaques, and, therefore, it cannot be
      considered early AD. Nicotinic receptor binding seems to be lost during the
      transition from MCI to AD.

PMID- 17172619
TI  - Multifocal motor neuropathy with conduction block: slow but not benign.
AB  - OBJECTIVE: To describe a patient with multifocal motor neuropathy with conduction
      block who had annual clinical and physiological examinations for 18 years but
      declined treatment for personal reasons. DESIGN: Case report. SETTING:
      Collaboration between 2 academic tertiary care hospitals. Patient One patient
      with multifocal motor neuropathy with conduction block. RESULTS: At age 44 years,
      there was weakness and wasting of the left biceps with conduction block in the
      left musculocutaneous and right ulnar nerves. The left median nerve was
      inexcitable. The right median, ulnar, and left peroneal nerves developed axonal
      change (loss of distal compound muscle action potential amplitude) at years 5,
      12, and 13. By 2005, new weakness had appeared in 20 muscles (16 in the arms); he
      could not use a keyboard, button buttons, or write his name. Nerves that
      initially showed conduction block became inexcitable over the course of the
      illness. CONCLUSIONS: Multifocal motor neuropathy with conduction block is a
      disease that may be "only" slowly progressive but is not always benign. Nerves
      showing conduction block may develop axonal change. Better markers for this
      disease are needed.

PMID- 17172620
TI  - Novel mutation in the PYGM gene resulting in McArdle disease.
AB  - BACKGROUND: McArdle disease is a common metabolic disorder characterized by
      marked exercise intolerance, premature fatigue during exertion, myalgia, and
      cramps. Despite the wide knowledge of the molecular basis of McArdle disease, few
      studies have used a physiological approach or explored the possibility of
      improving the exercise capacity of these patients. OBJECTIVES: To describe 3
      unrelated patients with McArdle disease with a novel mutation in the PYGM gene
      and to assess the physical capacity in 1 of them. DESIGN: Using molecular genetic
      approaches, we identified the underlying molecular defect in 3 patients with
      McArdle disease. Physical performance was evaluated in 1 patient by means of an
      exercise tolerance test on a bicycle ergometer. SETTING: Two university
      hospitals. Exercise physiology studies were performed in a university department.
      Patients The 3 patients showed common features of McArdle disease. They were
      definitively diagnosed by histochemistry, biochemistry, or molecular genetic
      analysis. RESULTS: All of the 3 patients were genetic compounds for the common
      Arg50Stop mutation and a novel c.13_14delCT mutation in the PYGM gene. The peak
      oxygen uptake (VO(2peak)) of the patient who performed the exercise test was only
      20.2 mL x kg(-1) x min(-1). CONCLUSIONS: Together with the novel mutation, there
      is a markedly decreased exercise capacity in a patient with McArdle disease,
      which could account for the profound alteration in the capacity for performing
      normal activities of daily living in this subpopulation.

PMID- 17172621
TI  - Effect of an R69C mutation in the myelin protein zero gene on myelination and ion
      channel subtypes.
AB  - BACKGROUND: Most mutations in the myelin protein zero gene (MPZ) typically cause
      a severe demyelinating/dysmyelinating neuropathy that begins in infancy or an
      adult-onset axonal neuropathy. Axonal degeneration in the late-onset H10P
      mutation may be caused by the disruption of axoglial interaction. OBJECTIVE: To
      evaluate sural nerve biopsy samples from a patient with early-onset Charcot-Marie
      Tooth disease type 1B caused by an arg69-to-cys (R69C) mutation. DESIGN AND
      PARTICIPANTS: Biopsies of sural nerves were performed 20 years apart in a patient
      with an R69C mutation (early onset). In addition, peripheral nerves were obtained
      from autopsy material from a patient with a T95M mutation (late onset). These
      nerves were analyzed using light microscopy of semithin sections, teased nerve
      fiber immunohistochemical analysis, electron microscopy, and immunologic electron
      microscopy. MAIN OUTCOME MEASURES: Pathological changes in sural nerve. RESULTS:
      Both R69C biopsy samples showed prominent demyelination and onion bulb formation,
      unlike the late-onset T95M mutation, which showed primarily axonal degeneration
      with no onion bulbs. The sural biopsy sample obtained 20 years earlier from the
      R69C patient showed minimal difference from the present sample, consistent with
      the lack of clinical progression during the 2 decades. Teased fiber
      immunohistochemical analysis of R69C revealed voltage-gated sodium channel
      subtype 1.8 expressions at the nodes of Ranvier around the areas of segmental
      demyelination. Internodal length in all R69C nerve fibers was invariably short
      (>94% of all internodes are <150 mum). CONCLUSIONS: Morphologic abnormalities in
      this early-onset R69C neuropathy were severe in childhood but progressed very
      slowly after adolescence. The switch to voltage-gated sodium channel subtype 1.8
      expression at the nodes may provide clues into the pathogenesis of this case of
      early-onset neuropathy, and the short internodes may contribute to the extremely
      slowed conduction velocities in this case (<10 m/s).

PMID- 17172622
TI  - Panic attacks in an individual with bilateral selective lesions of the amygdala.
AB  - OBJECTIVE: To describe the unique case of a patient with panic attacks and
      bilateral selective amygdala lesions due to Urbach-Wiethe disease. DESIGN: Case
      report. SETTING: Epilepsy Monitoring Unit, Medical University of Vienna. Patient
      A 38-year-old man with Urbach-Wiethe disease developed spontaneous panic attacks
      and depressive mood, which ceased after antidepressive treatment. INTERVENTIONS:
      Video electroencephalography monitoring, magnetic resonance imaging, and
      neuropsychological testing. RESULTS: Extended video electroencephalography
      monitoring excluded an epileptic etiology of the panic attacks. Results of
      cranial magnetic resonance imaging showed bilateral selective calcifications of
      the whole amygdaloid complex. Neuropsychological testing revealed selective
      memory impairment of autobiographic episodes with preserved memory for
      autobiographic facts. CONCLUSIONS: Our findings indicate that the occurrence of
      panic attacks does not critically depend on the integrity of the amygdala.
      Furthermore, the neuropsychological findings in our patient suggest that the
      amygdala represents an essential neural substrate for the processing of episodic
      autobiographic memories.

PMID- 17172623
TI  - Histoplasmosis presenting as an isolated spinal cord lesion.

PMID- 17172624
TI  - Tarlov cysts masquerading as peripheral neuropathy.

PMID- 17172625
TI  - Diffuse intracranial calcinosis: Fahr disease.

PMID- 17172626
TI  - Neutralizing antibodies against botulinum toxin a after a wasp sting.

PMID- 17172627
TI  - Data vs conclusions in the optic neuritis vaccination investigation.

PMID- 17172628
TI  - Determination of conversion factors from air kerma to operational dose equivalent
      quantities for low-energy X-ray spectra.
AB  - The conversion coefficients from air kerma to ICRU operational dose equivalent
      quantities for STUK's realisation of the X-radiation qualities N-15 to N-60 of
      the ISO narrow (N) spectrum series were determined by utilising X-ray spectrum
      measurements. The pulse-height spectra were measured using a planar high-purity
      germanium spectrometer and unfolded to fluence spectra using Monte Carlo
      generated data of the spectrometer response. To verify the measuring and
      unfolding method, the first and second half-value layers and the air kerma rate
      were calculated from the fluence spectra and compared with the values measured
      using an ionisation chamber. For each radiation quality, the spectrum was
      characterised by the parameters given in ISO 4037-1. The conversion coefficients
      from the air kerma to the ICRU operational quantities Hp(10), Hp(0.07), H'(0.07)
      and H*(10) were calculated using monoenergetic conversion coefficients at zero
      angle of incidence. The results are discussed with respect to ISO 4037-4, and
      compared with published results for low-energy X-ray spectra.

PMID- 17172629
TI  - Parent-adolescent communication and psychological symptoms among adolescents with
      chronically ill parents.
AB  - OBJECTIVE: To examine the psychological adjustment of adolescents living with a
      chronically ill parent and the relationship between psychological symptoms and
      communication with both their healthy and ill parents. METHOD: Adolescents,
      healthy parents, and ill parents from 38 families completed questionnaires
      regarding adolescent psychological symptoms, including posttraumatic stress
      symptoms, and parent-adolescent communication. RESULTS: Adolescent anxiety,
      depression, and behavior problems were within the subclinical ranges while
      approximately one-third of adolescents reported clinical levels of posttraumatic
      stress symptoms. Openness, but not problems, in communication between adolescents
      and their parents varied as a function of the parent's health status (healthy or
      ill) and parent sex. Adolescents reported poorer communication with healthy
      mothers; however only the quality of communication with healthy parents was
      related to adolescent psychological symptoms. CONCLUSIONS: Many adolescents with
      severely ill parents appear to experience clinically significant posttraumatic
      stress symptoms, therefore assessment for these symptoms in this population is
      important. Communication with a healthy parent may serve significant and unique
      functions for adolescents with ill parents, making communication between
      adolescents and their healthy parent a potentially useful target for clinical
      intervention.

PMID- 17172630
TI  - Integrating medical and psychological health care for children with atopic
      dermatitis.
AB  - OBJECTIVE: To present descriptive data from a hospital-based interdisciplinary
      program that provides integrated medical and psychological health-care for
      children with atopic dermatitis (AD). METHODS: Clinical records were reviewed for
      69 children seen in our program to examine parent-reported AD-related presenting
      concerns, as well as common problems and interventions addressed during family
      visits with the program psychologist. RESULTS: The most common presenting
      concerns included child itching and scratching and associated sleep problems.
      Parent initial request for a meeting with the program psychologist was not
      related to child disease severity, but was associated with child sleep problems
      and parent emotional and practical challenges in managing the child's condition.
      CONCLUSIONS: Results support the need for, acceptance of, and feasibility of
      providing integrated care for children with AD and their families. Changes to our
      clinical model based on study findings are discussed.

PMID- 17172631
TI  - Mortality among lifelong nonsmokers exposed to secondhand smoke at home: cohort
      data and sensitivity analyses.
AB  - Evidence is growing that secondhand smoke can cause death from several diseases.
      The association between household exposure to secondhand smoke and disease
      specific mortality was examined in two New Zealand cohorts of lifelong nonsmokers
      ("never smokers") aged 45-77 years. Individual census records from 1981 and 1996
      were anonymously and probabilistically linked with mortality records from the 3
      years that followed each census. Age- and ethnicity-standardized mortality rates
      were compared for never smokers with and without home exposure to secondhand
      smoke (based on the reported smoking behavior of other household members).
      Relative risk estimates adjusted for age, ethnicity, marital status, and
      socioeconomic position showed a significantly greater mortality risk for never
      smokers living in households with smokers, with excess mortality attributed to
      tobacco-related diseases, particularly ischemic heart disease and cerebrovascular
      disease, but not lung cancer. Adjusted relative risk estimates for all
      cardiovascular diseases were 1.19 (95% confidence interval: 1.04, 1.38) for men
      and 1.01 (95% confidence interval: 0.88, 1.16) for women from the 1981-1984
      cohort, and 1.25 (95% confidence interval: 1.06, 1.47) for men and 1.35 (95%
      confidence interval: 1.11, 1.64) for women from the 1996-1999 cohort. Passive
      smokers also had nonsignificantly increased mortality from respiratory disease.
      Sensitivity analyses indicate that these findings are not due to
      misclassification bias.

PMID- 17172632
TI  - Receptive fields in human visual cortex mapped with surface electrodes.
AB  - Most of our understanding of the functional organization of human visual cortex
      comes from lesion and functional imaging studies and by extrapolation from
      results obtained by neuroanatomical and neurophysiological studies in nonhuman
      primates. Although some single-unit and field potential recordings have been made
      in human visual cortex, none has provided quantitative characterization of
      spatial receptive fields (RFs) of individual sites. Here we use subdural
      electrodes implanted for clinical purposes to quantitatively measure response
      properties in different regions of human visual cortex. We find significant
      differences in RF size, response latency, and response magnitude for sites in
      early visual areas, versus sites in later stages of both the dorsal and ventral
      streams. In addition, we use this technique to estimate the cortical
      magnification factor in early human visual cortex. The spatial and temporal
      resolution of cortical surface recordings suggest that this technique is well
      suited to examine further issues in visual processing in humans.

PMID- 17172633
TI  - A comprehensive evaluation of cattle introgression into US federal bison herds.
AB  - Genetic introgression, especially from interspecies hybridization, is a
      significant threat to species conservation worldwide. In this study, 11 US
      federal bison populations were comprehensively examined for evidence of both
      mitochondrial and nuclear domestic cattle (Bos taurus) introgression.
      Mitochondrial introgression was examined using established polymerase chain
      reaction methods and confirmed through analysis of D-loop sequences. Nuclear
      introgression was assessed in 14 chromosomal regions through examination of
      microsatellite electromorph and sequence differences between bison and domestic
      cattle. Only one population was identified with domestic cattle mitochondrial DNA
      introgression. In contrast, evidence of nuclear introgression was found in 7
      (63.6%) of the examined populations. Historic accounts of bison transfers among
      populations were corroborated with evidence of introgressed DNA transmission.
      While neither nuclear nor mitochondrial domestic cattle introgression was
      detected in bison from Grand Teton National Park, Sully's Hill National Game
      Preserve, Wind Cave National Park, or Yellowstone National Park, adequate sample
      sizes were available only from the last 2 populations to allow for statistical
      confidence (>90%) in nuclear introgression detection limits. The identification
      of genetically unique and undisturbed populations is critical to species
      conservation efforts, and this study serves as a model for the genetic evaluation
      of interspecies introgression.

PMID- 17172634
TI  - Reduced frontal asymmetry of delta waves during all-night sleep in schizophrenia.
AB  - Delta wave deficits during sleep have been observed in patients with
      schizophrenia. Decreased slow-wave sleep is reported to be associated with
      negative symptoms. Frontal lobe dysfunction is also believed to underlie negative
      symptoms of schizophrenia. This study was designed to identify functional
      abnormalities in schizophrenia manifested on patients' electroencephalograms.
      Polysomnograph examinations were performed in 12 healthy male volunteers and 11
      male outpatients with schizophrenia. We investigated the laterality of frontal
      cortical delta waves in patients with schizophrenia and in healthy control
      subjects. Laterality of frontal cortex delta wave counts during all-night sleep
      was investigated by computer analysis. Total delta wave counts were lower in
      patients with schizophrenia than in control subjects. Control subjects showed
      significantly higher delta wave counts in the right frontal cortex than in the
      left. This asymmetry was not observed in patients with schizophrenia. These
      findings suggest that reduced right frontal delta wave dominance is involved in
      the pathophysiology of schizophrenia.

PMID- 17172635
TI  - Phylogenetic analyses of nuclear, mitochondrial, and plastid multigene data sets
      support the placement of Mesostigma in the Streptophyta.
AB  - All extant green plants belong to 1 of 2 major lineages, commonly known as the
      Chlorophyta (most of the green algae) and the Streptophyta (land plants and their
      closest green algal relatives). The scaly green flagellate Mesostigma viride has
      an important place in the debate on the origin of green plants. However, there
      have been conflicting results from molecular systematics as to whether Mesostigma
      diverges before the Chlorophyta/Streptophyta split or is an early diverging
      flagellate member of the Streptophyta. Previous studies employed either a limited
      taxon sampling (plastid and mitochondrial genomes) or a small number of
      phylogenetically informative sites (single nuclear genes). Here, we use large
      data sets from the nuclear (125 proteins; 29,319 positions), mitochondrial (33
      proteins; 6,622 positions), and plastid (50 proteins; 10,137 positions) genomes
      with an expanded taxon sampling (21, 13, and 28 species, respectively) to
      reevaluate the phylogenetic position of Mesostigma. Our study supports the
      placement of Mesostigma in the Streptophyta (as an early diverging lineage) and
      provides evidence that systematic biases have played a role in generating some of
      the previous conflicting results. Importantly, we demonstrate that using an
      increased taxon sampling as well as more realistic models of evolution allows
      increasing congruence among the nuclear, mitochondrial, and plastid data sets.

PMID- 17172637
TI  - The binding of Mss4 to alpha-integrin subunits regulates matrix metalloproteinase
      activation and fibronectin remodeling.
AB  - In four independent yeast two-hybrid screens with the integrin alpha-subunits
      alpha3A, alpha6A, alpha7A, and alpha7B, we identified the Mss4 protein, a
      nucleotide exchange factor for exocytic Rab GTPases, as a novel integrin
      interacting protein. We have previously shown that it binds to the conserved
      KXGFFKR region of integrin alpha-subunits located directly beneath the cell
      membrane. Here we show that the binding site for integrins on Mss4 is overlapping
      with those for Rab GTPases. Functional analysis of the Mss4/integrin interaction
      revealed its importance for activation of matrix metalloproteinases (MMPs) and
      remodeling of secreted extracellular matrix (ECM) proteins. The exocytosis of all
      the proteins analyzed, however, was unaffected. Furthermore, our data suggest
      that Mss4 drives the coordinated action of the MT1-MMP/integrin protein complex,
      thus regulating the presence and activation of MT1-MMP at newly formed filopodia
      and lamellipodia. This in turn facilitates the conversion of pro-MMPs to MMPs,
      resulting in cleavage and remodeling of ECM proteins. C2C12 myoblasts with stably
      down-regulated Mss4 showed a disturbed fibronectin remodeling during
      differentiation, resulting in malfunctioned myotube formation.

PMID- 17172636
TI  - Orphan nuclear receptor constitutive active/androstane receptor-mediated
      alterations in DNA methylation during phenobarbital promotion of liver
      tumorigenesis.
AB  - Altered DNA methylation is an epigenetic mechanism that plays a key role in the
      carcinogenesis process, and the nongenotoxic rodent hepatocarcinogen
      phenobarbital (PB) alters the methylation status of DNA in mouse liver. The
      constitutive active/androstane nuclear receptor (CAR) mediates half of the PB
      induced hepatic gene expression changes and it is essential for liver tumor
      promotion in PB-treated mice. Here, a technique involving methylation-sensitive
      restriction digestion, arbitrarily primed PCR, and capillary electrophoresis was
      utilized to detect PB-induced regions of altered DNA methylation (RAMs) in CAR
      wildtype (WT) mice that are sensitive to promotion by PB and resistant CAR
      knockout (KO) mice. The CAR WT mice developed preneoplastic lesions after 23
      weeks of PB treatment (precancerous) and liver tumors after 32 weeks, while the
      CAR KO mice did not develop tumors (Y. Yamamoto, et al., 2004, Cancer Res. 64,
      7197-7200). Our goal was to discern those RAMs which are playing important roles
      in tumor formation by comparing the RAMs that form in sensitive and resistant
      groups of mice. Using this novel approach, 42 unique RAMs were identified in the
      precancerous as compared to the CAR KO, 23-week PB-treated tissue. Of these 42
      RAMs, 14 carried forward to the tumor tissue, and additionally, 104 total unique
      RAMs were observed in the tumor tissue. These results indicate that there are
      unique RAMs occurring in the sensitive CAR WT mice and that a portion of these
      are seen in both the precancerous and tumor tissue. We hypothesize that these
      unique RAMs may be facilitating the tumorigenesis process, and these data support
      the view that DNA methylation plays a causative role in PB-induced tumorigenesis.

PMID- 17172638
TI  - The ubiquitin-protein ligase Nedd4 targets Notch1 in skeletal muscle and
      distinguishes the subset of atrophies caused by reduced muscle tension.
AB  - Ubiquitination-dependent proteolysis is a fundamental process underlying skeletal
      muscle atrophy. Thus, the role of ubiquitin ligases is of great interest. There
      are no focused studies in muscle on the ubiquitin ligase Nedd4. We first
      confirmed increased mRNA expression in rat soleus muscles due to 1-14 days of
      hind limb unloading. Nedd4 protein localized to the sarcolemmal region of muscle
      fibers. Hind limb unloading, sciatic nerve denervation, starvation, and diabetes
      led to atrophy of soleus, plantaris, and gastrocnemius muscles, but only unloaded
      and denervated muscles showed a marked increase in Nedd4 protein expression. This
      increase was strongly correlated with decreased Notch1 expression, a known target
      of Nedd4 in other cell types. Overexpression of dominant negative Nedd4 in soleus
      muscles completely reversed the unloading-induced decrease of Notch1 expression,
      indicating that Nedd4 is required for Notch1 inactivation. Overexpression of wild
      type Nedd4 in soleus muscles of weight bearing rats caused a decrease in Notch1
      protein, indicating that Nedd4 is sufficient for Notch1 down-regulation. To
      further show that Notch1 is a Nedd4 substrate in muscle, conditional
      overexpression of Nedd4 in C2C12 myotubes induced ubiquitination of Notch1. This
      is the first finding of a Nedd4 substrate in muscle and of an ubiquitin ligase,
      the activity of which distinguishes disuse from cachexia atrophy.

PMID- 17172639
TI  - Inhibition of the intestinal glucose transporter GLUT2 by flavonoids.
AB  - We tested whether the dominant intestinal sugar transporter GLUT2 was inhibited
      by intestinal luminal compounds that are inefficiently absorbed and naturally
      present in foods. Because of their abundance in fruits and vegetables, flavonoids
      were selected as model compounds. Robust inhibition of glucose and fructose
      transport by GLUT2 expressed in Xenopus laevis oocytes was produced by the
      flavonols myricetin, fisetin, the widely consumed flavonoid quercetin, and its
      glucoside precursor isoquercitrin [corrected]. IC50s for quercetin, myricetin,
      and isoquercitirin [corrected]were approximately 200- to 1000-fold less than
      glucose or fructose concentrations, and noncompetitive inhibition was observed.
      The two other major intestinal sugar transporters, GLUT5 and SGLT1, were
      unaffected by flavonoids. Sugar transport by GLUT2 overexpressed in pituitary
      cells and naturally present in Caco-2E intestinal cells was similarly inhibited
      by quercetin. GLUT2 was detected on the apical side of Caco-2E cells, indicating
      that GLUT2 was in the correct orientation to be inhibited by luminal compounds.
      Quercetin itself was not transported by the three major intestinal glucose
      transporters. Because the flavonoid quercetin, a food component with an excellent
      pharmacology safety profile, might act as a potent luminal inhibitor of sugar
      absorption independent of its own transport, flavonols show promise as new
      pharmacologic agents in the obesity epidemic.

PMID- 17172640
TI  - An arteriovenous loop in a protected space generates a permanent, highly
      vascular, tissue-engineered construct.
AB  - A major obstacle to 3-dimensional tissue engineering is incorporation of a
      functional vascular supply to support the expanding new tissue. This is overcome
      in an in vivo intrinsic vascularization model where an arteriovenous loop (AVL)
      is placed in a noncollapsible space protected by a polycarbonate chamber.
      Vascular development and hypoxia were examined from 3 days to 112 days by
      vascular casting, morphometric, and morphological techniques to understand the
      model's vascular growth and remodeling parameters for tissue engineering
      purposes. At 3 days a fibrin exudate surrounded the AVL, providing a scaffold to
      migrating inflammatory, endothelial, and mesenchymal cells. Capillaries formed
      between 3 and 7 days. Hypoxia and cell proliferation were maximal at 7 days,
      followed by a peak in percent vascular volume at 10 days (23.20+/-3.14% compared
      with 3.59+/-2.68% at 3 days, P<0.001). Maximal apoptosis was observed at 112
      days. The protected space and spontaneous microcirculatory development in this
      model suggest it would be applicable for in vivo tissue engineering. A temporal
      window in a period of intense angiogenesis at 7 to 10 days is optimal for
      exogenous cell seeding and survival in the chamber, potentially enabling specific
      tissue outcomes to be achieved.

PMID- 17172641
TI  - Cabin1 represses MEF2 transcriptional activity by association with a
      methyltransferase, SUV39H1.
AB  - Myocyte enhancer factor 2 (MEF2) plays pivotal roles in various biological
      processes, and its transcriptional activity is regulated by histone
      acetylation/deacetylation enzymes in a calcium-dependent fashion. A calcineurin
      binding protein 1 (Cabin1) has been shown to participate in repression of MEF2 by
      recruiting mSin3 and its associated histone deacetylases. Here, we report that
      histone methylation also takes a part in Cabin1-mediated repression of MEF2.
      Immunoprecipitate of Cabin1 complex can methylate histone H3 by association with
      SUV39H1. SUV39H1 increased Cabin1-mediated repression of MEF2 transcriptional
      activity in MEF2-targeting promoters. The SUV39H1 was revealed to bind to the 501
      900-amino acid region of Cabin1, which was distinct from its histone deacetylase
      recruiting domain. In addition, the Gal4-Cabin1-(501-900) alone repressed a
      constitutively active Gal4-tk-promoter, indicating that Cabin1 recruits SUV39H1
      and represses transcriptional activity. Finally, both SUV39H1 and Cabin1 were
      shown to bind on the MEF2 target promoter in a calcium-dependent manner. Thus,
      Cabin1 recruits chromatin-modifying enzymes, both histone deacetylases and a
      histone methyltransferase, to repress MEF2 transcriptional activity.

PMID- 17172642
TI  - LPA4/p2y9/GPR23 mediates rho-dependent morphological changes in a rat neuronal
      cell line.
AB  - Lysophosphatidic acid (LPA) is a potent lipid mediator that evokes a variety of
      biological responses in many cell types via its specific G protein-coupled
      receptors. In particular, LPA affects cell morphology, cell survival, and cell
      cycle progression in neuronal cells. Recently, we identified p2y(9)/GPR23 as a
      novel fourth LPA receptor, LPA(4) (Noguchi, K., Ishii, S., and Shimizu, T. (2003)
      J. Biol. Chem. 278, 25600-25606). To assess the functions of LPA(4) in neuronal
      cells, we used rat neuroblastoma B103 cells that lack endogenous responses to
      LPA. In B103 cells stably expressing LPA(4), we observed G(q/11)-dependent
      calcium mobilization, but LPA did not affect adenylyl cyclase activity. In LPA(4)
      transfectants, LPA induced dramatic morphological changes, i.e. neurite
      retraction, cell aggregation, and cadherin-dependent cell adhesion, which
      involved Rho-mediated signaling pathways. Thus, our results demonstrated that
      LPA(4) as well as LPA(1) couple to G(q/11) and G(12/13), whereas LPA(4) differs
      from LPA(1) in that it does not couple to G(i/o). Through neurite retraction and
      cell aggregation, LPA(4) may play a role in neuronal development such as
      neurogenesis and neuronal migration.

PMID- 17172643
TI  - Multiple histone deacetylases and the CREB-binding protein regulate pre-mRNA 3'
      end processing.
AB  - Trichostatin A (TSA), a specific inhibitor of histone deacetylases (HDACs),
      induces acetylation of various non-histone proteins such as p53 and alpha
      tubulin. We purified several acetylated proteins by the affinity to an anti
      acetylated lysine (AcLys) antibody from cells treated with TSA and identified
      them by mass spectrometry. Here we report on acetylation of CFIm25, a component
      of mammalian cleavage factor Im (CF Im), and poly(A) polymerase (PAP), a
      polyadenylating enzyme for the pre-mRNA 3'-end. The residues acetylated in these
      proteins were mapped onto the regions required for interaction with each other.
      Whereas CBP acetylated these proteins, HDAC1, HDAC3, HDAC10, SIRT1, and SIRT2
      were involved in in vivo deacetylation. Acetylation of the CFIm25 occurred
      depending on the cleavage factor complex formation. Importantly, the interaction
      between PAP and CF Im complex was decreased by acetylation. We also demonstrated
      that acetylation of PAP inhibited the nuclear localization of PAP by inhibiting
      the binding to the importin alpha/beta complex. These results suggest that CBP
      and HDACs regulate the 3'-end processing machinery and modulate the localization
      of PAP through the acetylation and deacetylation cycle.

PMID- 17172644
TI  - p38 mitogen-activated protein kinase plays an inhibitory role in hepatic
      lipogenesis.
AB  - Hepatic lipogenesis is the principal route to convert excess carbohydrates into
      fatty acids and is mainly regulated by two opposing hormones, insulin and
      glucagon. Although insulin stimulates hepatic lipogenesis, glucagon inhibits it.
      However, the mechanism by which glucagon suppresses lipogenesis remains poorly
      understood. In this study, we have observed that p38 mitogen-activated protein
      kinase plays an inhibitory role in hepatic lipogenesis. Levels of plasma
      triglyceride and triglyceride accumulation in the liver were both elevated when
      p38 activation was blocked. Expression levels of central lipogenic genes,
      including sterol regulatory element-binding protein-1 (SREBP-1), fatty acid
      synthase, hydroxy-3-methylglutaryl coenzyme A reductase, farnesyl pyrophosphate
      synthase, and cytochrome P-450-51, were decreased in liver by fasting and in
      primary hepatocytes by glucagon but increased by the inhibition of p38. In
      addition, we have shown that p38 can inhibit insulin-induced expression of key
      lipogenic genes in isolated hepatocytes. Our results in hepatoma cells
      demonstrate that p38 plays an inhibitory role in the activation of the SREBP-1c
      promoter. Finally, we have shown that transcription of the PGC-1beta gene, a key
      coactivator of SREBP-1c, was reduced in liver by fasting and in isolated
      hepatocytes by glucagon. This reduction was significantly reversed by the
      blockade of p38. Insulin-induced expression of the PGC-1beta gene was enhanced by
      the inhibition of p38 but suppressed by the activation of p38. Together, we have
      identified an inhibitory role for p38 in the transcription of central lipogenic
      genes, SREBPs, and PGC-1beta and hepatic lipogenesis.

PMID- 17172645
TI  - Pathogenesis of Mycobacterium avium infection: typical responses to an atypical
      mycobacterium?
AB  - Studying infections with Mycobacterium avium in mouse models has allowed the
      dissection of the antimycobacterial pathways of the mammalian host. Whereas the
      paradigm of cell-mediated immunity to intracellular pathogens has been confirmed,
      namely with regard to the pivotal roles of CD4+ T cells, macrophages, and the
      IL12-IFNgamma cytokine axis, atypical features have been uncovered such as the
      resistance to NO, the involvement of minor players in the induction of type 1
      protective immunity (such as TLR2, CD40, and CD30), and the development of
      immunopathology during the infection with highly virulent strains such as the
      development of caseous necrosis of granulomas or the progressive emergence of
      severe lymphopenia.

PMID- 17172647
TI  - Impact of lipoxin-mediated regulation on immune response to infectious disease.
AB  - During Toxoplasma gondii infection pro-inflammatory mediators such as IL-12, IFN
      gamma, and TNF are essential in controlling parasite growth. Those factors,
      however, can be detrimental to the host if produced in excess, and their effects
      need to be counterbalanced by the simultaneous induction of regulatory mediators
      including cytokines and antiinflammatory ecosanoids, lipoxins. Here, we review
      such novel molecules and the stop signaling pathways recently referred to as
      checkpoint controllers to keep proinflammatory response under control during
      chronic disease, as well as from the perspective of the pathogen, which pirates
      the host's lipoxygenase machinery to its own advantage as a probable immune
      escape mechanism.

PMID- 17172646
TI  - Immune response and immunotherapy to Cryptococcus infections.
AB  - Cryptococcus neoformans is a ubiquitous fungus that can cause lifethreatening
      infections during immunosuppressive states such as acquired immunodeficiency
      syndrome (AIDS) and after bone marrow transplantation (BMT). Infected individuals
      normally succumb to meningitis and meningoencephalitis caused by dissemination of
      C. neoformans to the brain. In this review, we analyze the current understanding
      of the interaction between host immune response and C. neoformans as well as the
      current state of immunotherapeutic strategies for treating cryptococcosis.

PMID- 17172648
TI  - TH2 cells in the pathogenesis of airway remodeling: regulatory T cells a
      plausible panacea for asthma.
AB  - T-helper type 2 (TH2) cells are one of the hallmarks of airway remodeling. The
      daunting task of regaining tolerance will be to regulate airway
      hyperresponsiveness (AHR) and remodeling in chronic asthma by balancing the
      ballet of TH1 and TH2 cells. The mechanism of tolerance appears to be modulated
      by a specialized subset of T cells called regulatory T cells (Tregs). Currently
      there are six subtypes of Tregs including CD4+CD25+ naturally occurring (N
      Tregs), inducible naive CD4+CD25- T cells (TR1), TR1 memory phenotype, T-helper
      type 3 (TH3), CD4-CD25+DX5+ natural killer T cells (TRNKT), and CD4-CD25+CD8+
      cytotoxic T cells (TRCTC). The development of Tregs is controversial as to
      whether they occur in the thymus or peripheral lymphoid tissue. Studies have
      shown that NTregs are generated in the thymus and TR1 cells occur in the
      periphery. Nevertheless, Tregs express an arsenal of molecular membrane markers:
      CD3, CD25, CD62L, CD69, BTLA, GITR, ICOS, Neuroplin- 1 (Nrp-1), and PD-1.
      However, the most definitive marker is Forkhead Winged-Helix Transcriptional
      Factor Box p3 (Foxp3). The suppression of N-Tregs occurs by cell-to-cell contact,
      and low levels of IL-10 and moderate levels of TGF-beta, but the primary
      mechanism involves the sequestration and activation of neighboring naive CD4+CD25
      T cells to become TR1 cells. In contrast, TR1 cells exert their suppressive
      properties by copious secretion of IL-10 and TGF- beta. These suppressive
      mechanisms occur by the inhibition of IL-2 production and the promotion of cell
      cycle arrest. The development of this specialized subset of T cells is an enigma,
      but their understanding will provide a plausible panacea for asthma.

PMID- 17172649
TI  - Advances in potential M-protein peptide-based vaccines for preventing rheumatic
      fever and rheumatic heart disease.
AB  - Rheumatic fever (RF) and rheumatic heart disease (RHD) are postinfectious
      complications of an infection (or repeated infection) with the Gram-positive
      bacterium, Streptococcus pyogenes (also known as group A streptococcus, GAS). RF
      and RHD are global problems and affect many indigenous populations of developed
      countries and many developing countries. However, RF and RHD are only part of a
      larger spectrum of diseases caused by this organism. The development of a vaccine
      against GAS has primarily targeted the abundant cell-surface protein called the M
      protein. This review focuses on different M-protein-based-subunit vaccine
      approaches and the different delivery technologies used to administer these
      vaccine candidates in preclinical studies.

PMID- 17172650
TI  - Following the TRAIL to apoptosis.
AB  - Apoptosis, programmed cell death, eliminates injured or harmful cells. It can
      mediate its response through the actions of death ligands including TRAIL. TRAIL,
      a member of TNF superfamily, induces apoptosis of transformed cells through the
      action of death domain receptors DR-4 and DR5. It directly induces apoptosis
      through an extrinsic pathway, which involves the activation of caspases. TRAIL
      also is able to prevent apoptosis through the actions of its decoy receptors DcR
      1 and DcR-2. Various regulators of TRAIL include FADD, IAPs, Bcl-2s, p53, and
      FLIPs. TRAIL is present in cells involved in asthma including eosinophils, mast
      cells, fibroblasts, and airway epithelial cells. It is expressed in airway
      remodeling and may be linked with the pathways of transforming growth factor
      beta1, which is thought to cause damage to the epithelium. The repair process of
      the epithelium is hindered as a result of increased apoptosis induced by TGF
      beta1, which overlaps with the pathways of TRAIL. Analogs of TRAIL could have
      therapeutical applications for asthma. TRAIL is also seen as the basis for a
      "miracle" drug for cancer because of its ability to selectively kill cancer
      cells.

PMID- 17172654
TI  - Proceedings from the 7th PEACe Conference on Protein Expression in Animal Cells,
      September 18-22, 2005, Crete, Greece.

PMID- 17172651
TI  - The CD94/NKG2 family of receptors: from molecules and cells to clinical
      relevance.
AB  - Immune responses must be tightly regulated to avoid hyporesponsiveness on one
      hand or excessive inflammation and the development of autoimmunity
      (hyperresponsiveness) on the other hand. This balance is attained through the
      throttling of activating signals by inhibitory signals that ideally leads to an
      adequate immune response against an invader without excessive and extended
      inflammatory signals that promote the development of autoimmunity. The CD94/NKG2
      family of receptors is composed of members with activating or inhibitory
      potential. These receptors are expressed predominantly on NK cells and a subset
      of CD8+ T cells, and they have been shown to play an important role in regulating
      responses against infected and tumorigenic cells. In this review, we discuss the
      current knowledge about this family of receptors, including ligand and receptor
      interaction, signaling, membrane dynamics, regulation of gene expression and
      their roles in disease regulation, infections, and cancer, and bone marrow
      transplantation.

PMID- 17172653
TI  - Regulations and roles of the interleukin-1 receptor associated kinases (IRAKs) in
      innate and adaptive immunity.
AB  - The interleukin-1 receptor associated kinases (IRAKs) are critically involved in
      the IL-1R/Toll-like receptor (TLR)-mediated signal transduction processes and
      therefore regulate cellular innate immune responses. Four IRAK members have been
      identified in the human genome (IRAK-1, 2, M, and 4), which seem to play distinct
      roles. Recent studies further suggest that some of the IRAK members may also
      participate in T cell and B cell signaling and regulate adaptive immunity. Given
      the critical and complex roles IRAK proteins play, it is not surprising that
      genetic variations in human IRAK genes have been found to be linked with various
      human inflammatory diseases. This review intends to summarize the recent advances
      regarding the biochemical regulations of various IRAK proteins and their cellular
      functions in mediating innate and adaptive immunity.

PMID- 17172655
TI  - Epidermal growth factor receptor-induced activator protein 1 activity controls
      density-dependent growth inhibition in normal rat kidney fibroblasts.
AB  - Density-dependent growth inhibition secures tissue homeostasis. Dysfunction of
      the mechanisms, which regulate this type of growth control is a major cause of
      neoplasia. In confluent normal rat kidney (NRK) fibroblasts, epidermal growth
      factor (EGF) receptor levels decline, ultimately rendering these cells
      irresponsive to EGF. Using an activator protein (AP)-1 sensitive reporter
      construct, we show that AP-1 activity is strongly decreased in density-arrested
      NRK cells, but is restored after relaxation of densitydependent growth inhibition
      by removing neighboring cells. EGF could not induce AP-1 activity or S-phase
      entry in density-arrested cells, but could do so after pretreatment with retinoic
      acid, which enhances EGF receptor expression. Our results support a model in
      which the EGF receptor regulates density-dependent growth control in NRK
      fibroblasts, which is reflected by EGF-induced mitogenic signaling and consequent
      AP-1 activity.

PMID- 17172656
TI  - Oncogenes are to lose control on signaling following mutation: should we aim off
      target?
AB  - Rationalized cancer therapy aims at blocking overactive signaling pathways in
      cancer cells using kinase inhibitors. Essential for its success is the
      identification of suitable drug targets. Several recent reports have shown that
      by using control analysis, one can determine which component of a pathway is in
      control of its output. However, it has not been analyzed how a mutation in an
      oncogene affects the extent to which the various components are important. Are
      the same proteins still important after an oncogene has been activated? In the
      present study, we show that, upon mutation, oncogenes such as mutant kinases tend
      to lose part of their control on signaling. On the other hand, some of the
      nonmutated genes may become more important, when compared to the situation before
      the mutation. This may imply that, perhaps paradoxically, signaling proteins
      encoded by nonmutated genes should make better drug targets against cancer.

PMID- 17172652
TI  - Promise and pitfalls in animal-based asthma research: building a better
      mousetrap.
AB  - Asthma is one of the leading chronic diseases in the world today. An essential
      component of the asthma research endeavor is the animal-based experimental
      disease system, which provides knowledge that is not attainable through study of
      patients alone. Animal research is especially valuable for elucidating
      pathophysiology, drug testing, and as an adjunct for interpreting the results of
      human clinical trials. However, controversies surrounding animal systems data and
      at the interface between animal and human studies raise questions regarding the
      true utility of experimental asthma research. We consider here the considerable
      promise and important limitations of animal-based systems and their prospects for
      the future study asthma.

PMID- 17172657
TI  - Analyzing molecular reaction networks: from pathways to chemical organizations.
AB  - Pathways are typically the central concept in the analysis of biochemical
      reaction networks. A pathway can be interpreted as a chain of enzymatical
      reactions performing a specific biological function. A common way to study
      metabolic networks are minimal pathways that can operate at steady state called
      elementary modes. The theory of chemical organizations has recently been used to
      decompose biochemical networks into algebraically closed and self-maintaining
      subnetworks termed organizations. The aim of this paper is to elucidate the
      relation between these two concepts. Whereas elementary modes represent the
      boundaries of the potential behavior of the network, organizations define
      metabolite compositions that are likely to be present in biological feasible
      situations. Hence, steady state organizations consist of combinations of
      elementary modes. On the other hand, it is possible to assign a unique (and
      possibly empty) set of organizations to each elementary mode, indicating the
      metabolites accompanying the active pathway in a feasible steady state.

PMID- 17172658
TI  - Transcriptome and proteome profiling to understanding the biology of high
      productivity CHO cells.
AB  - A combined transcriptome and proteome analysis was carried out to identify key
      genes and proteins differentially expressed in Chinese hamster ovary (CHO) cells
      producing high and low levels of dhfr-GFP fusion protein. Comparison of
      transcript levels was performed using a proprietary 15K CHO cDNA microarray chip,
      whereas proteomic analysis was performed using iTRAQ quantitative protein
      profiling technique. Microarray analysis revealed 77 differentially expressed
      genes, with 53 genes upregulated and 24 genes downregulated. Proteomic analysis
      gave 75 and 80 proteins for the midexponential and stationary phase,
      respectively. Although there was a general lack of correlation between mRNA
      levels and quantitated protein abundance, results from both datasets concurred on
      groups of proteins/genes based on functional categorization. A number of genes
      (20%) and proteins (45 and 23%) were involved in processes related to protein
      biosynthesis. We also identified three genes/proteins involved in chromatin
      modification. Enzymes responsible for opening up chromatin, Hmgn3 and Hmgb1, were
      upregulated whereas enzymes that condense chromatin, histone H1.2, were
      downregulated. Genes and proteins that promote cell growth (Igfbp4, Ptma, S100a6,
      and Lgals3) were downregulated, whereas those that deter cell growth (Ccng2,
      Gsg2, and S100a11) were upregulated. Other main groups of genes and proteins
      include carbohydrate metabolism, signal transduction, and transport. Our findings
      show that an integrated genomic and proteomics approach can be effectively
      utilized to monitor transcriptional and posttranscriptional events of mammalian
      cells in culture.

PMID- 17172659
TI  - On the effect of transient expression of mutated eIF2alpha and eIF4E eukaryotic
      translation initiation factors on reporter gene expression in mammalian cells
      upon cold-shock.
AB  - There are a growing number of reports on the beneficial effects of
      subphysiological temperature in vitro culturing (27-35 degrees C) of mammalian
      cells on recombinant protein yield. However, this effect is not conserved across
      cell lines and target products, and our understanding of the molecular
      mechanism(s) responsible for increased recombinant protein yield upon reduced
      temperature culturing of mammalian cells is poor. What is known is that mammalian
      cells respond to cold-shock by attenuating global cap-dependent translation.
      Here, we have investigated the hypothesis that the cap-dependent attenuation of
      mRNA translation upon cold-stress of in vitro-cultured mammalian cells can be
      prevented, or at least alleviated, by overexpressing mutant translation
      initiation factors in Chinese hamster ovary and HeLa cells. We have shown that
      the transient coexpression of either an eIF2alphaSer51 Ala51 mutant or an
      eIF4ESer209 Glu209 mutant with firefly luciferase affects luciferase expression
      levels in a cell line and temperature dependent manner. Further, regardless of
      the coexpression of initiation factors, transient reporter gene expression was
      enhanced at subphysiological temperatures (<37 degrees C), suggesting that
      reduced temperature cultivation can be used to improve the yield of recombinant
      protein during transient expression. The implications of these results upon cell
      engineering strategies involving manipulation of the translational apparatus for
      the enhancement of recombinant protein synthesis upon cold-shock are discussed.

PMID- 17172660
TI  - Toward more efficient protein expression: keep the message simple.
AB  - Optimization of gene coding-sequence, including preferred codon usage and removal
      of cryptic splice sites and mRNA-destabilizing motifs, has been shown to improve
      recombinant protein production of different proteins. Here, we present data to
      show that gene optimization can also be used to improve the production of a
      complex macromolecule, namely an antibody. When applied to the heavy and light
      chain genes of our model antibody, we found that greater numbers of high
      producing transfectants as well as increased levels of protein production were
      observed (approximately 1.5-fold). In this test model, production was improved
      even though the antibody has previously been demonstrated to give high expression
      in stably transfected cells (up to 5 g/L in bioreactors). Because the parental
      heavy chain sequence contained introns, and the process of gene optimization is
      most efficiently performed on sequences without introns, we demonstrated that
      removal of introns in the coding sequence had no effect on the quantity of
      antibody produced. All constructs were evaluated using Lonza's glutamine
      synthetase gene expression vectors in Chinese hamster ovary cells. Our findings
      suggest that significant improvements in product yields can be achieved by gene
      optimization, which may facilitate the processing and translation of gene
      transcripts.

PMID- 17172661
TI  - Optimization of baculovirus transduction on FreeStyle293 cells for the generation
      of influenza B/Lee/40.
AB  - Recombinant baculovirus expression vectors derived from the Autographa
      californica nuclear polyhedrosis virus can serve as efficient gene-transfer
      vehicles for transient expression of recombinant proteins in a wide range of
      mammalian cell types and are able to produce multisubunit particles such as
      viruses or virus like particles. In this study, we constructed eight recombinant
      baculoviruses each containing one of the influenza B/Lee/40 virus genes in a
      bidirectional expression cassette for simultaneous mRNA and viral RNA
      transcription. Baculoviruses were transduced into FreeStyle293 in combination
      with the specific histone deacetylase inhibitor trichostatin A (TSA).
      Cotransduction conditions were optimized with a set of five baculoviruses
      (influenza B/Lee/40 PB1, PB2, PA, and NP and the control construct NCR-NS-minus
      sense orientated encoding green fluorescent protein [rGFP]), which led to GFP
      expression in each host cell transduced with all five constructs. Based on the
      optimization with five constructs, transduction with eight baculoviruses was
      performed at MOI 50 and 100 with high yield stocks and 1 microM TSA and led to
      successful rescue of infectious influenza B/Lee/40 viruses.

PMID- 17172663
TI  - Development of transfection and high-producer screening protocols for the CHOK1SV
      cell system.
AB  - To date, the FDA has approved 18 monoclonal antibody (MAb) therapeutic drugs with
      targets ranging from asthma and rheumatoid arthritis to leukemia. Many of these
      approved products are produced in Chinese hamster ovary cells (CHO) making CHO a
      significant and relevant host system. We studied the applicability of CHOK1SV
      cells as a potential host cell line for MAb production in terms of timelines,
      achievable titers, transfectant stability, and reproducibility. CHOK1SV,
      developed by Lonza Biologics, is a suspension, protein-free-adapted CHOK1
      derivative utilizing the glutamine synthetase (GS) gene expression system.
      CHOK1SV expresses the GS enzyme endogenously; thus, positive transfectants were
      obtained under the dual selection of methionine sulfoximine (MSX) and glutamine
      free media. We examined outgrowth efficiencies, specific productivities, and
      achievable batch titers of three different IgG MAbs transfected into CHOK1SV.
      Reducing the MSX concentration in the initial selection medium resulted in a
      decreased incubation time required for transfectant colonies to appear. Specific
      productivities of "high-producers" ranged between 11 and 49 pg/c/d with batch
      titers ranging from 105 to 519 mg/L. Transfectant stability and the effects of
      MSX also were investigated, which indicated that the addition of MSX was
      necessary to maintain stable MAb production. Cell growth was stable regardless of
      MSX concentration.

PMID- 17172662
TI  - Expression of human coagulation factor VIII in a human hybrid cell line, HKB11.
AB  - Loss of coagulation factor VIII (FVIII) function results in a bleeding disorder,
      hemophilia A, which requires FVIII replacement therapy. Owing to its large size
      and complexity, the expression level of recombinant FVIII is two to three orders
      of magnitude lower than other recombinant proteins produced in mammalian cell
      lines. To understand cellular factors limiting FVIII expression, we studied the
      expression of FVIII in a human cell line, HKB11 (a hybrid cell line of HEK293 and
      a human B cell line). In comparison with other cell lines, such as HEK293 and BHK
      21, HKB11 showed increased FVIII expression levels. With unamplified, pooled
      stable cells, FVIII expression in HKB11 cells was 8- to 30-fold higher than the
      other cell lines tested. In this study, HKB11 clones expressing varying levels of
      FVIII were analyzed and FVIII secreted from these clones had similar specific
      activity. Characterization of these clones by immunofluorescence staining,
      Western blotting analysis, and flow cytometry showed that high-producing cells
      not only secreted more active FVIII but also accumulated more FVIII protein
      intracellularly. FVIII expression appears to be controlled by the rates of
      transcription, translation, and secretion, but transcription and translation may
      play more important roles than secretion in determining expression level in HKB11
      cells. FACS analysis of live cells showed that the high-producing clones also had
      more FVIII on the HKB11 cell surface than low-producing cells, thus opening the
      possibility of using FACS to select high-producing cell lines. Expression levels
      of the chaperone protein Hsp70 and antiapoptotic proteins such as Bcl-2 and Bcl
      xL were similar among HKB11 clones with different FVIII productivity. In
      conclusion, HKB11 is an efficient host cell line for expression of FVIII and
      possibly other recombinant proteins. Systematic approaches, such as gene
      expression profiling by DNA microarray, will be necessary to understand the
      global changes in the cells producing recombinant proteins.

PMID- 17172664
TI  - Serum-free suspension large-scale transient transfection of CHO cells in WAVE
      bioreactors.
AB  - Here, we report the development of a large-scale transient expression platform
      utilizing Chinese hamster ovary (CHO) cells. The majority of recombinant proteins
      and antibodies that are produced for preclinical models and clinical trials are
      expressed in stably transfected CHO cells. A protocol for transient transfection
      of CHO cells that is rapid, reproducible, and cost-effective would therefore
      streamline the process from research to development and help avoid any potential
      host species induced variation in the molecule of interest. CHO cells were
      adapted to grow in serum-free suspension conditions in spinner flask cultures in
      a proprietary in-house developed growth medium. In developing this transient
      transfection protocol, the parameters optimized included the transfection reagent
      of choice, the cell density at the time of transfection, the plasmid DNA
      concentration, and the transfection reagent concentration. Using this optimized
      protocol, we have expressed recombinant proteins, including antibodies, at an
      expression level of up to 9.4 mg/L. We also report transient transfections from
      500 mL working volume (w.v.) up to 20 L w.v. in a WAVE bioreactor. Using this
      optimized protocol, it is possible to rapidly (within 10 d) produce up to 100 mg
      of recombinant protein for further study.

PMID- 17172665
TI  - LONG R3IGF-I as a more potent alternative to insulin in serum-free culture of
      HEK293 cells.
AB  - LONG R3IGF-I, an analogue of insulin-like growth factor (IGF)-I, was specifically
      engineered for use in biopharmaceutical protein production in mammalian cells.
      LONG R3IGF-I is capable of supporting the growth and survival of Chinese hamster
      ovary cells in serum-free media at concentrations at least 200-fold lower than
      required for insulin. LONG R3IGF-I also acts as a more potent growth and survival
      factor than either insulin or native IGF-I in SF culture of human embryonic
      kidney (HEK293) cells. To investigate the basis of the enhanced potency of LONG
      R3IGF-I we have examined the mechanism of action of these mitogens in HEK293
      cells. All mitogens tested were found to activate the Type I IGF receptor (IGF
      IR) and insulin receptor (IR) in a dose-responsive manner. However, the level of
      activation of both receptors after stimulation with LONG R3IGF-I, at lower
      concentrations, was greater than with either insulin or IGF-I. The greater
      potency of LONG R3IGF-I in activating the IR, despite having a low affinity for
      IRs, suggests the presence of heterotetrameric IGF-IR/IR dimers. Interestingly,
      the decrease in IGF-IR activation at higher concentrations of LONG R3IGF-I
      suggests that the dose-response curve may be bell-shaped.

PMID- 17172666
TI  - Structural genomics: the ultimate approach for rational drug design.
AB  - Structural genomics can be defined as structural biology on a large number of
      target proteins in parallel. This approach plays an important role in modern
      structure-based drug design. Although a number of structural genomics initiatives
      have been initiated, relatively few are associated with integral membrane
      proteins. This indicates the difficulties in expression, purification, and
      crystallization of membrane proteins, which has also been confirmed by the
      existence of some 100 high-resolution structures of membrane proteins among the
      more than 30,000 entries in public databases. Paradoxically, membrane proteins
      represent 60-70% of current drug targets and structural knowledge could both
      improve and speed up the drug discovery process. In order to improve the success
      rate for structure resolution of membrane proteins structural genomics networks
      have been established.

PMID- 17172667
TI  - Chlamydomonas reinhardtii: a protein expression system for pharmaceutical and
      biotechnological proteins.
AB  - Recombinant proteins have become more and more important for the pharmaceutical
      and chemical industry. Although various systems for protein expression have been
      developed, there is an increasing demand for inexpensive methods of large-scale
      production. Eukaryotic algae could serve as a novel option for the manufacturing
      of recombinant proteins, as they can be cultivated in a cheap and easy manner and
      grown to high cell densities. Being a model organism, the unicellular green alga
      Chlamydomonas reinhardtii has been studied intensively over the last decades and
      offers now a complete toolset for genetic manipulation. Recently, the successful
      expression of several proteins with pharmaceutical relevance has been reported
      from the nuclear and the chloroplastic genome of this alga, demonstrating its
      ability for biotechnological applications.

PMID- 17172669
TI  - High-level secretion of growth hormone by retrovirally transduced primary human
      keratinocytes: prospects for an animal model of cutaneous gene therapy.
AB  - A gene therapy clinical trial for treatment of growth hormone (GH) deficiency has
      not been reached yet, but several strategies using different gene transfer
      methodologies and animal models have been developed and showed successful
      results. We have set up an ex vivo gene therapy protocol using primary human
      keratinocytes transduced with an efficient retroviral vector (LXSN) encoding the
      human (hGH) or mouse GH (mGH) genes. These stably modified cells presented high
      in vitro expression levels of hGH (7 microg/106 cells/d) and mGH (11 microg/106
      cells/d) after selection with geneticin. When the hGH-secreting keratinocytes
      were grafted onto immunodeficient dwarf mice (lit/scid), hGH levels in the
      circulation were about 0.2-0.3 ng/mL during a 12-d assay and these animals
      presented a significant body weight increase (p < 0.01) compared to the control.
      Substitution of conventional grafting methodologies with organotypic raft
      cultures revealed a peak value of up to 20 ng mGH/mL in the circulation of
      grafted lit/scid mice at 1 h postimplantation, followed by a rapid decline to
      baseline (approximately 2 ng/mL) within 24 h. One week after grafting, however,
      the cultured excised implants still presented approx 45% of their original in
      vitro secretion efficiency. Further studies are being carried out to identify the
      main factor(s) that still constitute one of the major impediments to the success
      of this promising model of cutaneous gene therapy.

PMID- 17172670
TI  - The conundrum between immunological memory to adenovirus and their use as vectors
      in clinical gene therapy.
AB  - In the context of clinical gene transfer using viral vectors, the risk of memory
      antivector immunity is often poorly appreciated. The immunological past of the
      patient, the site of injection, and the vector dose will play intertwined and
      decisive roles in the safety and efficacy of treatment. To circumvent the
      drawbacks due to the ubiquitous human adenovirus (HAd) memory immunity, we
      believe that vectors derived from canine adenovirus type 2 (CAV-2) will be more
      clinically useful than those derived from HAds based, in part, on the potential
      lack of immunological memory. CAV-2 is not a human pathogen in spite of the
      approx 100,000 yr of cohabitation of humans with dogs. During the last 8 yr, we
      found that CAV-2 vectors preferentially transduced neurons in the central nervous
      system (CNS) of several species, and had a surprisingly efficient level of
      axoplasmic transport. CAV-2 vectors also lead to greater than 1 yr transgene
      expression in the immunocompetent rat CNS-without immunosuppression. However,
      more immediate harm can be caused to a patient via an acute and/or chronic vector
      induced cellular infiltration in the CNS than by the normal progression of most
      neurodegenerative disorders. In this context, we continue to assess the clinical
      potential of CAV-2. This mini-review addresses our analysis of the interaction of
      CAV-2 vectors with human memory immunity and monocyte-derived dendritic cells.

PMID- 17172668
TI  - Large-scale transfection of mammalian cells for the fast production of
      recombinant protein.
AB  - Recombinant proteins (r-proteins) are increasingly important in fundamental
      research and for clinical applications. As many of these r-proteins are of human
      or animal origin, cultivated mammalian cells are the host of choice to ensure
      their functional folding and proper posttranslational modifications. Large-scale
      transfection of human embryonic kidney 293 or Chinese hamster ovary cells is now
      an established technology that can be used in the production of hundreds of
      milligram to gram quantities of a r-protein in less than 1 mo from cloning of its
      cDNA. This chapter aims to provide an overview of large-scale transfection
      technology with a particular emphasis on calcium phosphate and polyethylenimine
      mediated gene transfer.

PMID- 17172672
TI  - Regulation of gene expression in mouse embryos and its embryonic cells through
      RNAi.
AB  - The ability to direct cell differentiation of embryo-derived cells should have
      considerable practical applications. A prerequisite for success is the
      availability of robust tools that allows efficient knockdown of specific genes to
      elucidate gene function and direct differentiation. Loss-of-function studies in
      the mouse have traditionally been carried out using gene knockout animals to
      obtain mutant embryonic cells. Despite improvements in this technology, it still
      remains a laborious method. In addition, the use of knockout for studying
      preimplantation embryonic cells is limited due to maternal contributions. RNA
      interference (RNAi) is a powerful genetic approach for specific gene silencing of
      target genes in which 21-23 nt small interfering RNAs work as sequence-specific
      RNAi mediators. Using RNAi approaches, gene function has been eliminated in mouse
      embryonic stem cells and carcinoma cells to direct cell differentiation. In mouse
      oocytes and embryos, RNAi eliminated both maternal and zygotic transcripts and
      disturbed normal development.

PMID- 17172671
TI  - Long-term gene expression in dividing and nondividing cells using SV40-derived
      vectors.
AB  - Among the goals of gene therapy is long-term expression of delivered transgenes.
      Recombinant Tagdeleted SV40 vectors (rSV40s) are especially well suited for this
      purpose. rSV40s deliver transgene expression that endures for extended periods of
      time in tissue culture and in vivo, in both dividing and nondividing cells. These
      vectors are particularly effective in transducing some cell types that have been
      almost unapproachable using other gene delivery systems, such as quiescent
      hematopoietic progenitor cells and their differentiated derivatives. Other
      cellular targets include neurons, brain microglia, hepatocytes, dendritic cells,
      vascular endothelium, and others. Because rSV40s do not elicit neutralizing
      antibodies they are useful for in vivo gene delivery in settings where more than
      one administration may be desirable. The key characteristics of these vectors
      include their high production titers and therefore suitability for large cell
      pools, effectiveness in delivering intracellular proteins, and untranslated RNAs,
      maintenance of transgene expression at constant levels for extended times,
      suitability for constitutive or conditional promoters and for combinatorial gene
      delivery and ability to integrate into genomes of both dividing and nondividing
      cells.

PMID- 17172674
TI  - Two-dimensional polyacrylamide gel electrophoresis for cardiovascular proteomics.
AB  - The majority of cardiovascular proteomic investigations reported to date have
      employed two-dimensional gel electrophoresis (2DE) with immobilized pH gradients
      to separate the sample proteins, combined with quantitative computer analysis to
      detect differentially expressed proteins and mass spectrometry technologies to
      identify proteins of interest. In spite of the development of novel gel-free
      technologies, 2DE remains the only technique that routinely can be applied to
      parallel quantitative expression profiling of large sets of complex protein
      mixtures, such as those represented by cardiovascular cell and tissue lysates.
      This chapter details a procedure for large-format 2DE, and its variations, that
      has been successfully applied in cardiovascular proteomic research.

PMID- 17172675
TI  - Analyzing the cardiac muscle proteome by liquid chromatography-mass spectrometry
      based expression proteomics.
AB  - Cardiomyopathies are diseases of the heart resulting in impaired cardiac muscle
      function, which can lead to heart dilation or overt heart failure. These diseases
      represent a major cause of global morbidity and death. Innovative preventive and
      therapeutic measures are urgently needed for early detection, categorization, and
      treatment of patients at risk of cardiomyopathy. These developments will require
      a more complete understanding of the molecular effects of impaired cardiac
      function, even prior to overt disease. The use of gel-free expression proteomics
      in the detailed analysis of cardiac tissues should yield significant insight into
      the pathophysiology of these diseases.

PMID- 17172673
TI  - The unfolded protein response.
AB  - The unfolded protein response (UPR) is a signal transduction network activated by
      inhibition of protein folding in the endoplasmic reticulum (ER). The UPR
      coordinates adaptive responses to this stress situation, including induction of
      ER resident molecular chaperone and protein foldase expression to increase the
      protein folding capacity of the ER, induction of phospholipid synthesis,
      attenuation of general translation, and upregulation of ER-associated degradation
      to decrease the unfolded protein load of the ER, and an antioxidant response.
      Upon severe or prolonged ER stress the UPR induces apoptosis to eliminate
      unhealthy cells from an organism or a population. In this review, I will
      summarize our current knowledge about signal transduction pathways involved in
      transducing the unfolded protein signal from the ER to the nucleus or the
      cytosol.

PMID- 17172676
TI  - Two-dimensional differential gel electrophoresis of rat heart proteins in
      ischemia and ischemia-reperfusion.
AB  - Ischemia-reperfusion injury occurs in acute myocardial infarction,
      cardiopulmonary bypass surgery, and heart transplantation. However the precise
      mechanisms still remain unclear. In order to identify proteins that are involved
      in ischemia-reperfusion injury, we compared precipitated 100,000g fractions of
      normal, ischemic, and ischemic-reperfused rat hearts using two-dimensional (2D)
      difference gel electrophoresis (2D-DIGE). 2D-DIGE is reliable method to define
      quantitative protein differences, especially when subtle protein changes are
      under investigation. In this study, six spots that changed more than twofold and
      two additional spots related to these spots were detected. Five of the spots were
      identified by matrix-assisted laser desorption/ionization time of flight mass
      spectrometry as protein disulfide isomerase, one as 60 kDa heat-shock protein,
      and two as elongation factor Tu.

PMID- 17172677
TI  - Analysis of antihypertensive drugs in the heart of animal models: a proteomic
      approach.
AB  - Arterial hypertension is the most frequent chronic disease and it is an important
      cause of morbidity and mortality in the developed world. Arterial hypertension is
      associated with such adverse effects as accelerated arteriosclerosis and
      pathological left ventricular hypertrophy, among others. The molecular mechanisms
      affecting left ventricular hypertrophy remain mostly unknown. The advent of
      proteome profiling has facilitated the elucidation of disease-associated
      proteins, paving the way for molecular diagnostics and the identification of
      novel therapeutic targets. We explored the proteomic profile of pathological left
      ventricular hypertrophy in comparison with normal heart in a model of rats and
      investigated the proteomic changes in response to different antihypertensive
      regimens in order to elucidate their cardioprotective effects. Here we describe
      in depth the protocol for this type of study.

PMID- 17172678
TI  - A solubility optimization protocol for two-dimensional gel electrophoresis of
      cardiac tissue.
AB  - We outline a strategy for the optimization of buffer conditions for the
      solubilization, extraction, and isoelectric focusing (IEF) of proteins from
      cardiac tissue for two-dimensional gel electrophoresis (2DE). This strategy,
      which involves altering both the extraction and IEF buffers, allows one to ensure
      representation of the proteome that is as complete as possible. Initial buffer
      choices are given, as well as basic protocols for modifications. Although these
      conditions have been effectively demonstrated for human myocardium, in principle
      this procedure can be used for the initial screen of any new sample of tissue or
      cultured cells.

PMID- 17172679
TI  - A method for the effective depletion of albumin from cellular extracts:
      application to human myocardium.
AB  - Proteomic analysis of large numbers of proteins is assisted if each protein
      species is present at approximately equal concentrations. As such, the extraction
      of proteins from tissue samples should be designed to maintain a limited dynamic
      range in the concentration of proteins present. However, in many tissue extracts
      a high concentration of serum albumin exists from tissue perfusion and/or an
      inability to effectively rinse the tissue owing to surgical limitations. The
      analysis of these tissues would be assisted if contaminating serum albumin could
      be reduced. This chapter outlines a protocol for the effective reduction of serum
      albumin levels from human myocardium extracts enriched for soluble cytoplasmic
      proteins.

PMID- 17172680
TI  - Subcellular fractionation.
AB  - The successful combination of highly sensitive mass spectrometry and pre
      fractionation techniques has provided a powerful tool to detect dynamic changes
      in low abundant regulatory proteins at the organelle level. Subcellular
      fractionation, being flexible, adjustable (both in cell and tissues), and
      allowing the analysis of proteins in their physiologic/intracellular context, has
      become the most commonly used preparative/enrichment method. This chapter
      introduces state-of-the-art subcellular fractionation protocols and briefly
      discuss their suitability, advantages, and limitations.

PMID- 17172681
TI  - Subfractionation of heart tissue: the "in sequence" myofilament protein
      extraction of myocardial tissue.
AB  - Proteomic analysis of heart tissue is complicated by the large dynamic range of
      its proteins. The most abundant proteins are the myofilament proteins, which
      comprise the contractile apparatus. This chapter describes a protocol for
      fractionation of heart tissue that extracts the myofilament proteins into a
      separate sample fraction, allowing analysis of lower-abundance proteins.
      Importantly, this is performed in a manner that is compatible with two
      dimensional electrophoresis and high-performance liquid chromatography, two of
      main technologies of proteomics. The method produces three fractions based on
      solubility at different pHs: (1) cytoplasmic-enriched extract (neutral pH), (2)
      myofilament-enriched extract (acidic pH), and (3) membrane protein-enriched
      pellet. Fractionation of heart tissue in this manner provides the basis for in
      depth proteomic analysis.

PMID- 17172682
TI  - Optimization of cardiac troponin I pull-down by IDM affinity beads and SELDI.
AB  - Cardiac troponin I (cTnI) is a key regulator of cardiac muscle contraction. Upon
      myocardial cell injury, cTnI is lost from the cardiac myocyte and can be detected
      in serum, in some cases with specific disease-induced modifications, making it an
      important diagnostic marker for acute myocardial injury. Presently, hospital
      laboratories use enzyme-linked immunosorbent assays to detect cTnI, but this type
      of analysis lacks information about modified forms of protein (degradation or
      phosphorylation) that may give a more specific diagnosis from either serum or
      biopsies. Because cardiac and serum tissues are widely used for proteomic
      analysis, it is important to detect these cTnI posttranslational modifications.
      Therefore, we have chosen to optimize the enrichment and detection of cTnI
      protein by IDM Affinity Bead pull-down and surface-enhanced laser
      desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS or SELDI)
      analyses. By adjusting the chemical compositions of the buffers, we have retained
      antibody specificity and enriched for different forms of cTnI and its associated
      proteins.

PMID- 17172683
TI  - Proteomic analysis of the subunit composition of complex I (NADH:ubiquinone
      oxidoreductase) from bovine heart mitochondria.
AB  - Complex I from the inner membranes of mammalian mitochondria is a complicated
      membrane-bound assembly of redox centers (flavin mononucleotide cofactor, iron
      sulphur centers) and at least 46 different proteins. The hydrophobic nature of
      its membrane-bound subunits and the complexity of subunit content present a
      substantial analytical challenge. The complete protein chemical analysis of
      complex I purified from bovine mitochondria required the resolution of subunits
      by one-dimensional and two-dimensional electrophoresis, reverse-phase
      chromatography, and combinations of these techniques. These subunits were
      characterized by mass spectrometry (MS)-based protein identification methods,
      requiring both peptide mass fingerprinting and amino acid sequencing by tandem
      MS. The components were identified also and characterized by measurements of
      subunit molecular mass. These strategies have provided a comprehensive view of
      the subunit content of the intact complex, its structural domains, and stable
      subunit modifications.

PMID- 17172684
TI  - Identification of targets of phosphorylation in heart mitochondria.
AB  - Whereas most strategies in proteomics deal with changes in protein levels,
      posttranslational modifications often represent pathological consequences at the
      molecular level without changes in abundance and, therefore represent a critical
      phenomenon to study. The present report elucidates an approach to studying one
      such posttranslational modification, phosphorylation, which is an important event
      in a variety of signaling cascades initiated in the heart in response to
      physiological and pathological stimuli. Comparison of phosphorylation profiles in
      different conditions, including drug treatments, receptor stimulation or
      blockade, and so forth, may lead to identification of relevant targets of signal
      transduction cascades. Furthermore, it may be possible to devise similar schemes
      to detect the subset of proteins modified by ubiquitinylation, lipid acylation,
      and so forth, and to compare differential patterns. Phosphorylation of
      mitochondrial targets is increasingly being recognized. Mitochondria are critical
      targets of a number of signaling pathways and therefore it is important to
      develop suitable methods to detect phosphorylation of mitochondrial targets. One
      approach is to perform in vitro phosphorylation in a reconstituted system of
      cytosol and mitochondria.

PMID- 17172685
TI  - Characterization of the human atheroma plaque secretome by proteomic analysis.
AB  - Atherosclerosis is one of the most common causes of death in developed countries.
      Atherosclerosis is an inflammatory process that results in the development of
      complex lesions or plaques that protrude into the arterial lumen. Plaque rupture
      and thrombosis result in the acute clinical complications of myocardial
      infarction and stroke. Although certain risk factors (dyslipidemias, diabetes,
      hypertension) and humoral markers of plaque vulnerability (C-reactive protein,
      interleukin-6, -10 and -18, CD-40L) have been identified, a highly sensitive and
      specific biomarker or protein profile, which could provide information on the
      stability/vulnerability of atherosclerotic lesions, remains to be identified.
      Recently, we have described a novel strategy consisting in the proteomic analysis
      of proteins released by normal and atherosclerotic arterial walls in culture.
      This method enables harvesting of proteins that are only secreted by pathological
      or normal arterial walls. By focusing only on the secreted proteins found in the
      tissue culture media, there is an intended bias toward those molecules that would
      have a higher probability of later being found in plasma. Using this approach, we
      have shown that carotid atherosclerotic plaques cultured in vitro are able to
      secrete proteins, and also that a differential pattern of protein secretion of
      normal arteries vs pathological ones has been observed. In this chapter, the
      proteomic analysis of the human atheroma plaque secretome is described.

PMID- 17172686
TI  - Characterization of HSP27 phosphorylation sites in human atherosclerotic plaque
      secretome.
AB  - Atherosclerosis is one of the main causes of death in developed countries.
      Atheroma plaque formation is promoted by the interaction between the cells
      conforming the arterial wall, smooth muscle cells, and endothelial cells,
      together with lipoproteins and inflammatory cells (mainly macrophages and T
      lymphocytes). These interactions can be mediated by proteins secreted from these
      cells, which therefore exert an important role in the atherosclerotic process. We
      recently described a novel strategy for the characterization of the human
      atherosclerotic plaque secretome, combining two-dimensional gel electrophoresis
      and mass spectrometry (MS). Among the identified proteins, two isoforms of heat
      shock protein 27 (HSP27), a protein recently described as a potential biomarker
      of atherosclerosis, were detected. However, the putative mechanisms in which
      HSP27 isoforms could be involved in the atherosclerotic process are unknown.
      Thus, the role that phosphorylated HSP27 could play in the atherosclerotic
      process is actually under study. The present work shows the strategies employed
      to characterize the phosphorylation in the HSP27 secreted by atheroma plaque
      samples. The application of liquid chromatography tandem mass spectrometry
      (MS/MS), as well as the combination of immobilized metal affinity chromatography
      methodology with matrix-assisted laser desorption/ionization MS/MS are described.

PMID- 17172687
TI  - Western array analysis of human atherosclerotic plaques.
AB  - High-throughput immunoblotting or Western array screening of tissue is a unique
      advancement in proteomics that may help researchers in their quest to elucidate
      the proteins and signaling pathways involved in complex human pathologies such as
      atherosclerosis. The technique entails polyacrylamide gel electrophoresis and
      Western blotting followed by screening of the blots with hundreds of high-quality
      antibodies that are combined into unique cocktails. Because each monoclonal
      antibody identifies a unique target among the array of thousands of proteins
      displayed on the Western blot, subnanogram quantities of proteins with altered
      expression can be readily detected. This approach of proteome analysis avoids the
      limitations of traditional high-throughput protein screening techniques such as
      two-dimensional gel electrophoresis and mass spectrometry.

PMID- 17172688
TI  - The proteome of endothelial cells.
AB  - Endothelial cells form a continuous monolayer lining the inside face of all blood
      vessels, and present the ability to selectively control vascular permeability.
      The endothelium is involved in a wide variety of normal physiological and
      pathological processes. The endothelial dysfunction occurs under activation
      conditions, with the acquisition of many new functional, inflammatory, and immune
      properties, and as a consequence, endothelial cells display many different
      transcription profiles. We describe here the isolation and culture of the most
      useful model of human umbilical vein endothelial cells, and undertake the
      proteomic analysis under both basal quiescent condition and activated by
      stimulation with a proinflammatory cytokine. Series of two-dimensional
      electrophoresis have allowed us to detect a total of close to 600 polypeptide
      spots using 4.0-7.0 pH range in both culture conditions. We have selected 233
      proteins by cross-matching the gels, and found that 70% showed an increase and
      30% a decrease of expression levels in activated cells. Subsequent identification
      of 35 altered peptides is made by matrix-assisted laser desorption and ionization
      time-of-flight mass spectrometry, as well as a study of posttranslational
      modifications. These global findings may contribute to understand the effects of
      pathological stimuli and the mechanisms that regulate vascular diseases.

PMID- 17172689
TI  - Proteomic study of caveolae and rafts isolated from human endothelial cells.
AB  - Caveolae and rafts are specialized microdomains of the endothelial cell plasma
      membrane, which play an important role in signal transduction, transcellular
      transport, and cholesterol homeostasis. The dynamic protein composition of these
      subcellular lipid domains has been implicated in a variety of patho-physiological
      states of the vasculature, and is receiving increased attention. As a result of
      the membranous composition and abundance of insoluble intrinsic and membrane
      associated proteins, determination of the raft/caveolae subproteome composition
      requires specially adapted methods. In this chapter, we present a straightforward
      protocol to obtain comprehensive and reliable peptide mixtures from this
      subproteome by subcellular fractionation and both one-dimensional and two
      dimensional gel electrophoresis. These mixtures allow dynamic monitoring of
      composition and posttranslational modification of the raft/caveola subproteome
      using peptide mass fingerprinting and direct peptide sequencing tandem mass
      spectrometry.

PMID- 17172690
TI  - Proteomic identification of S-nitrosylated proteins in endothelial cells.
AB  - Nitric oxide (NO) produced in endothelial cells exerts important roles in the
      vascular system. In recent years, posttranslational modifications induced by NO
      have been increasingly studied and, among them, cysteine modification by S
      nitrosylation (also called S-nitrosation) has been hypothesized to represent a
      relevant mechanism for cell signaling. Thus, knowledge of the proteins that can
      be S-nitrosylated in endothelial cells will help to better understand the
      possible role of this modification. We describe a protocol to identify the S
      nitrosylome or S-nitrosoproteome of endothelial cells, based on the specific
      derivatization of the S-nitrosylation, substituting it by a biotinylation, and
      the purification of the biotinylated proteins.

PMID- 17172691
TI  - The proteome and secretome of human arterial smooth muscle cell.
AB  - Smooth muscle cells (SMCs) play a crucial role in cardiovascular diseases.
      Proteomic analysis using two-dimensional gel electrophoresis (2DE) associated
      with mass spectrometry allows characterization of the proteome and secretome of
      human smooth muscle. The presence of a distinct SMC population in the arterial
      wall implies that under normal conditions, SMCs are phenotypically heterogeneous.
      Intracellular and secreted proteins from a primary culture of SMCs obtained from
      patients undergoing coronary bypass surgery were analyzed using 2DE in order to
      determine their specific features. The 2D reference maps show that SMCs are
      involved in a wide range of biological functions. They could constitute a useful
      tool for a wide range of investigators involved in vascular biology, allowing
      them to investigate SMC protein changes associated with cardiovascular disorders
      or environmental stimuli.

PMID- 17172692
TI  - Real-time in vivo proteomic identification of novel kinase substrates in smooth
      muscle.
AB  - Relaxation of smooth muscle can occur through agonists (such as nitric oxide)
      that activate guanylyl cyclase and stimulate the production of cGMP, activating
      its target, cGMP-dependent protein kinase (PKG). This kinase can raise the Ca2+
      threshold for contraction, thus causing Ca2+ desensitization, but the mechanism
      for this event is not completely understood. Ca2+ sensitization/desensitization
      pathways are essential for maintenance of normal smooth muscle tone, and
      abnormalities in these pathways have been shown to be key components in the
      pathogenesis of diseases such as hypertension and asthma in humans. Our
      laboratory has devised a proteomic method to specifically address the question of
      what proteins are early phosphorylation targets in calcium desensitization. Using
      ileum smooth muscle, we metabolically labeled the muscle with (32P)
      orthophosphate, permeabilized the muscle, established constant calcium
      concentrations, and stimulated with 8-bromo-cGMP, which activates PKG. Proteins
      whose phosphorylation state changed in response to cGMP at constant levels of
      calcium were separated with two-dimensional gel electrophoresis, identified by
      autoradiography, and sequenced with nanospray mass spectrometry. Using this
      technique, we identified a previously uncharacterized PKG phosphoprotein, which
      we have termed CHASM (Calponin Homology Smooth Muscle protein). Using
      physiological muscle bath contraction studies, we have validated CHASM as a
      component of calcium desensitization pathways in smooth muscle.

PMID- 17172693
TI  - Proteomic analysis of vascular smooth muscle cells treated with ouabain.
AB  - Apoptosis of vascular smooth muscle cells (VSMC) plays an important role in
      remodeling the vessel walls, one of the major determinants of long-term blood
      pressure elevation and an independent risk factor for cardiovascular morbidity
      and mortality. Apoptosis in VSMC can be inhibited by inversion of the
      intracellular [Na+]/[K+] ratio after the sustained blockage of the Na+,K+-ATPase
      by ouabain. Using two-dimensional gel electrophoresis followed by tandem mass
      spectroscopy, we compared proteomes of control VSMC and of those with ouabain
      inhibited Na+,K+-ATPase and found that ouabain treatment led to overexpression of
      numerous soluble and membrane-bound proteins. Among proteins, which showed the
      highest level of ouabain-induced expression, we identified mortalin (also known
      as GRP75 or PBP-74), a member of the heat shock protein 70 superfamily and a
      marker for cellular mortal and immortal phenotypes. Further experiments showed
      that mortalin RNA and protein levels are induced in ouabain-treated VSMC, and
      that transient transfection of cells with mortalin cDNA inhibited serum
      deprivation-induced apoptosis via inactivation of the tumor suppressor gene, p53.

PMID- 17172694
TI  - Isolation and culture of adult mouse cardiac myocytes.
AB  - Cardiac myocytes are activated by hormonal and mechanical signals and respond in
      a variety of ways, from altering contractile function to inducing cardio
      protection and growth responses. The use of genetic mouse models allows one to
      examine the role of cardiac-specific and other genes in cardiac function,
      hypertrophy, cardio-protection, and diseases such as ischemia and heart failure.
      However, studies at the cellular level have been hampered by a lack of suitable
      techniques for isolating and culturing calcium-tolerant, adult mouse cardiac
      myocytes. We have developed a straightforward, reproducible protocol for
      isolating and culturing large numbers of adult mouse cardiac myocytes. This
      protocol is based on the traditional approach of retrograde perfusion of
      collagenase through the coronary arteries to digest the extracellular matrix of
      the heart and release rod-shaped myocytes. However, we have made modifications
      that are essential for isolating calcium-tolerant, rod-shaped adult mouse cardiac
      myocytes and maintaining them in culture. This protocol yields freshly isolated
      adult mouse myocytes that are suitable for biochemical assays and for measuring
      contractile function and calcium transients, and cultured myocytes that are
      suitable for most biochemical and signaling assays, as well as gene transduction
      using adenovirus.

PMID- 17172695
TI  - Proteomic analysis of foam cells.
AB  - Foam cells are characteristic pathological cells in the lesions of
      atherosclerosis. Previous works have established macrophage-derived foam cell
      model to study the central role of the foam cells, and analyzed the protein
      expression profiles in foam cells. The reported in vitro foam cell model was
      established by incubating the human U937 cells with oxidized low-density
      lipoprotein. The global changes in protein expressions between U937 foam cell and
      normal U937 cells were measured with two-dimensional gel electrophoresis, and
      some interested proteins were tryptic-digested and then identified via mass
      spectrometry after capillary liquid chromatography separation. Some of the
      identified proteins were validated via the Internet links to the U937 proteomic
      map provided from the Expasy Proteomics server (http://us.expasy.org). The
      experimental data can provide potential markers during the inflammatory reactions
      for atherosclerotic studies.

PMID- 17172696
TI  - Isolation of the platelet releasate.
AB  - This chapter describes an approach to isolate, separate, and identify the
      contents of the platelet releasate, a fraction highly enriched for platelet
      granular and exosomal contents. Investigation into such a fraction will improve
      our understanding of platelet interactions with other cells, vascular remodeling,
      coagulation, and vessel growth.

PMID- 17172697
TI  - Enrichment of phosphotyrosine proteome of human platelets by immunoprecipitation.
AB  - Proteomics offers the opportunity to comprehensively investigate the anucleate
      platelet. Here, we present a detailed procedure for enrichment by
      immunoprecipitation, using the monoclonal antibody 4G10, of the dynamic
      phosphotyrosine proteome of human platelets. Such an approach offers the
      possibility of capturing the dynamic tyrosine phosphorylation events that occur
      upon platelet activation and aggregation, with an aim to identify novel signaling
      proteins.

PMID- 17172698
TI  - Characterization of circulating human monocytes by proteomic analysis.
AB  - We describe a simple method for isolation of human blood monocytes with the high
      purity required for proteomic analysis, which avoids contamination by other blood
      cells (platelets and lymphocytes) and the most abundant plasma proteins (albumin
      and immunoglobulins). Blood monocytes were purified by gradient centrifugation
      followed by positive selection with monoclonal antibodies coupled to paramagnetic
      beads. This method is compatible with flow cytometry, which was used to assess
      the purity of the cell population. After solubilization of monocytes, the
      proteins where analyzed by two-dimensional gel electrophoresis in several pH
      ranges. Image analysis of gels allowed the reproducible detection and
      quantification of the spots present in the gel. This method is useful for
      clinical studies of monocytes from a large number of patients, owing to its
      rapidity and reproducibility, which permits comparative analysis of normal vs
      pathological samples and allows follow up of the expressed proteins of monocytes
      from each patient.

PMID- 17172699
TI  - Cardiovascular biomarker discovery by SELDI-TOF mass spectrometry.
AB  - Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry
      (TOFMS) allows for rapid differential proteomic analysis of various experimental
      conditions. In the first step of retention chromatography, the proteome to be
      analyzed is fractionated based on the biochemical properties of the proteins or
      peptides of which it is composed. TOF-MS separates the proteins according to
      their molecular mass and charge (m/z in which conditions are optimized to obtain
      single charged proteins: z = 1). The most discriminating conditions are used to
      validate differential peaks on a larger number of samples. Once the biomarker is
      statistically validated, its identification is performed by reproducing the
      chromatographic conditions that are appropriate for its retention on spin
      columns, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      trypsin digestion of the band of interest, and subsequent peptide mapping after
      MS. It may be necessary to determine part of the amino acid sequence of the
      protein of interest to confirm its identity.

PMID- 17172700
TI  - Detection of biomarkers of stroke using SELDI-TOF.
AB  - With a mean weight of 1500 g containing around 10 billion neurons, the adult
      brain represents about 2% of the total body mass, but requires 20% of the total
      energy produced. It consumes continuously 150 g of glucose and 72 L of oxygen
      every 24 h. A few minutes interruption of this supply can lead to dramatic brain
      damage. Manifestations and consequences of stroke depend on the location and
      extent of the lesions. A vascular cerebral accident, also called stroke or brain
      attack, is an interruption of the blood supply owing to either occlusion
      (ischemic stroke) or rupture (hemorrhagic stroke) of a blood vessel to any part
      of the brain, with an occurrence of around 80% for the ischemic type. Stroke has
      a devastating impact on public health and remains the third leading cause of
      death and the first leading cause of long-term disability in industrialized
      countries. An early diagnosis of the cerebral accident associated with an
      appropriate treatment would reduce the risk of death and enhance the chances of
      recovery. When the diagnosis of stroke is established, the physician needs to
      know the nature (ischemic or hemorrhagic), the extent, and the location of the
      accident in order to orient patients and to give them most suitable treatment.
      Because no specific and unique symptoms or early blood diagnostic markers are
      currently available, it was of a great interest to develop new approaches in the
      research and discovery area of new early diagnosis and prognosis markers of
      stroke.

PMID- 17172701
TI  - Depletion of high-abundance proteins in plasma by immunoaffinity subtraction for
      two-dimensional difference gel electrophoresis analysis.
AB  - Blood plasma is believed the most complex human-derived proteome, containing
      other tissue proteome subsets. Almost all body cells communicate with the plasma,
      either directly or through tissues or biological fluids, and many of these cells
      release at least a part of their content into the plasma upon damage or death. A
      comprehensive, systematic characterization of the plasma proteome in the healthy
      and diseased states will greatly facilitate the development of biomarkers for
      early disease detection, clinical diagnosis, and therapy. However, the
      characterization of human plasma proteome is a very complicated task, owing to
      the wide dynamic range of concentration that separates the most abundant proteins
      and the less common ones (10-12 orders of magnitude). The removal of its
      predominant proteins by affinity chromatography using an FPLC system improves the
      presence of low-abundance proteins in two-dimensional gel electrophoresis (2DE).
      The "Multiple Affinity Removal System" (Agilent Technologies) retains albumin,
      IgG, IgA, haptoglobin, transferrin, and antitrypsin with high specificity and
      reproducibility. After depletion, we have independently analyzed the flow-through
      (low-abundance proteins), and the retained fractions, by 2DE (4.0-7.0 pH range).
      Image analysis of the stained gels revealed that more than 300 spots appeared in
      the retained fraction and about 1800 spots appeared in the nonretained fraction.
      This methodology is a valuable tool for clinical proteomics, because its
      reproducibility allows comparative studies and quantitative analysis by 2DE or
      two-dimensional differential gel electrophoresis of plasma or sera samples from
      subjects with different pathological or physiological conditions. In addition,
      the method allows the comparison of experimental results from different
      laboratories.

PMID- 17172702
TI  - A rapid, economical, and reproducible method for human serum delipidation and
      albumin and IgG removal for proteomic analysis.
AB  - Serum is a readily available source for diagnostic assays, but the identification
      of disease-specific serum biomarkers has been impeded by the dominance of human
      serum albumin (HSA) and immunoglobulin G (IgG) in the serum proteome. Therefore,
      in order to observe lower-abundance serum proteins, removal or depletion of at
      least these two proteins is required. However, the depletion method needs to be
      inexpensive and reproducible. We describe such a protocol that combines
      delipidation by centrifugation, IgG removal with Protein G Sepharose, and HSA
      depletion with sodium chloride/ethanol precipitation. The protocol is streamlined
      to increase reproducibility and is compatible with many proteomic platforms,
      including two-dimensional gel electrophoresis, and high-performance liquid
      chromatography either offline or coupled online with a mass spectrometer. The
      reproducible depletion of lipids, IgG, and HSA permits a higher load of the
      remaining serum proteins, facilitating the identification of disease biomarkers.

PMID- 17172703
TI  - Mitoproteome: human heart mitochondrial protein sequence database.
AB  - The human mitochondrial proteome database has been developed by deriving data
      from a combination of public repositories and experimental and computational
      prediction methods. The experimental data is derived from highly purified
      mitochondria from human heart tissue, whereas predictions have been performed by
      MITOPRED, a genome-scale method for the prediction of nucleus-encoded
      mitochondrial proteins. Mitochondrial protein sequences from different sources
      have been clustered to generate a nonredundant dataset. Annotations related to
      the protein function, structure, disease association, pathways, and so on are
      collected from a number of public databases using commonly used UNIX and Perl
      scripts. This chapter provides a detailed description of various data sources and
      methods used to download, curate, parse, and generate meaningful annotations from
      primary as well as derived databases.

PMID- 17172704
TI  - Techniques to decipher molecular diversity by phage display.
AB  - Combinatorial phage display technology may be applied to decipher the molecular
      diversity of peptide binding specificity to isolated proteins, purified
      antibodies, cell surfaces, intracellular/cyto-domains, and blood vessels in vivo.
      The application of such a strategy ranges from identifying receptor-ligand pairs
      and antigen binding sites to understanding the progression of diseases by their
      differential expression patterns and developing therapeutic targeting strategies.
      Different strategies can be used to isolate peptides from diverse libraries
      displayed on the surface of bacteriophage by exposing the library to a target
      molecule or organ, washing away nonbinding phage, eluting and amplifying the
      bound phage for multiple round use, and then analyzing the peptide sequences of
      the enriched phage. The following methods first outline the construction of a
      phage library and then delineate various in vitro and in vivo biopanning
      applications to probe isolated integrins, purified antibodies, cell surface
      molecules, and vascular endothelial cells.

PMID- 17172705
TI  - Druggable signaling proteins.
AB  - In normal cells, signaling pathways are tightly regulated. However, when they are
      aberrantly activated, certain pathways are capable of causing diseases. In many
      tumors, the aberrantly activated signaling proteins include members of the
      epidermal growth factor receptor family, the Ras proteins, protein kinase C
      isoenzymes, BCR-ABL fusion protein as well as transcription factors such as
      signal transducers and activators of transcriptions and Myc. Accordingly,
      deregulation of these signaling proteins holds promise for the development of new
      anticancer drugs. Studies in vitro and in disease-relevant models demonstrated
      that blocking the activation of a key target in a constitutively activated
      signaling pathway could reverse disease phenotype. Moreover, constitutive
      activation of the target alone is sufficient to induce relevant disease
      phenotype. Notably, the most dramatic therapeutic advances in cancer therapy
      during the last decade have come from agents targeted against active thyrosine
      kinases. These include imatinib (anti-BCR-ABL), gefitinib (anti-EGF receptor),
      and herpetin (anti-ErbB-2). Here, some selected validated and drugable targets
      are summarized.

PMID- 17172706
TI  - DNA methylation and histone modifications in patients with cancer: potential
      prognostic and therapeutic targets.
AB  - Epigenetics, a combination of DNA modifications, chromatin organization, and
      variations in its associated proteins, configure a new entity that regulates gene
      expression throughout methylation, acetylation, and chromatin remodeling. In
      addition to silencing as a result of mutations, loss of heterozygosity, or
      classical genetic events epigenetic modification symbolizes essential early
      events during carcinogenesis and tumor development. The reversion of these
      epigenetic processes restoring normal expression of tumor-suppressor genes has
      consequently become a new therapeutic target in cancer treatment. Aberrant
      patterns of epigenetic modifications will be, in a near future, crucial
      parameters in cancer diagnosis and prognosis.

PMID- 17172707
TI  - Wnt signaling as a therapeutic target for cancer.
AB  - The Wnt/beta-catenin signaling pathway is tightly regulated and has important
      functions in development, tissue homeostasis, and regeneration. Deregulation of
      Wnt/beta-catenin signaling is frequently found in various human cancers. Eighty
      percent of colorectal cancers alone reveal activation of this pathway by either
      inactivation of the tumor-suppressor gene adenomatous polyposis coli or mutation
      of the proto-oncogene beta-catenin. Activation of Wnt/beta-catenin signaling has
      been found to be important for both initiation and progression of cancers of
      different tissues. Therefore, targeted inhibition of Wnt/beta-catenin signaling
      is a rational and promising new approach for the therapy of cancers of various
      origins.

PMID- 17172708
TI  - NG2/HMP proteoglycan as a cancer therapeutic target.
AB  - Neuroepithelial cells of the central nervous system constitute neuroglia
      (astrocytes, oligodendrocytes, and microglia), ependyma, and neurons, which make
      up the stromal cells of the brain. The stromal tissue organization of the brain
      is tightly regulated, but occasionally the signals that define the normal
      contexts become disrupted and result in cancer. Malignant progression is then
      maintained by cross-talks between the tumor and its stroma, where the activated
      stroma nurtures the proliferative and invasive neoplastic cells, by providing
      neovasculature, extracellular matrix components, and stimulatory growth factors.
      The NG2/HMP plays a major role in tumor-stroma activation through alterations in
      cellular adhesion, migration, proliferation, and vascular morphogenesis.
      Therapeutic strategies specifically targeting NG2/HMP may be useful in
      normalizing the tumor stroma and may reduce the toxic side effects when used in
      combination with conventional treatments.

PMID- 17172709
TI  - Heterotrimeric G proteins and disease.
AB  - Heterotrimeric G proteins attached to the cell membrane convey signals from G
      protein-coupled receptors in response to stimulation by a number of hormones,
      neurotransmitters, chemokines, and pharmacological agents to intracellular
      signaling cascades. The heterotrimeric G proteins are also located in the cell
      interior, and receptor-independent mechanisms may elicit their activation. Thus,
      G proteins may possibly exert cellular functions other than acting as signaling
      transducers. There is also increasing evidence for roles in different diseases
      including infections, inflammation, neurological diseases, cardiovascular
      diseases, cancer, and endocrine disorders. This review describes characteristics
      of the heterotrimeric G proteins, evidence for their involvement in different
      diseases, and outlines some of the therapeutic options utilizing G protein
      targets.

PMID- 17172710
TI  - High-mobility group box-1 isoforms as potential therapeutic targets in sepsis.
AB  - High-mobility group box-1 (HMGB1) protein was originally described as a nuclear
      DNA-binding protein that functions as a structural cofactor critical for proper
      transcriptional regulation and gene expression. Recent studies indicate that
      damaged, necrotic cells liberate HMGB1 into the extracellular milieu where it
      functions as a proinflammatory cytokine. Indeed, HMGB1 represents a novel family
      of inflammatory cytokines composed of intracellular proteins that can be
      recognized by the innate immune system as a signal of tissue damage.
      Posttranslational modifications of HMGB 1 determine its interactions with other
      proteins and modulate its biological activity. However, very little is known
      about how these posttranslational modifications of HMGB1 affect its extracellular
      inflammatory activity and pathological potential. These studies can provide more
      efficient therapeutic strategies directed against specific HMGB1 isoforms.
      Therapeutic strategies against these specific HMGB1 isoforms can serve as models
      for more efficient therapeutic strategies against rheumatoid arthritis or sepsis.
      This article reviews the recent studies on HMGB1 regulation and their impact on
      the inflammatory activity and pathological contribution of HMGB 1 to infectious
      and inflammatory disorders.

PMID- 17172711
TI  - Antisense oligonucleotides: target validation and development of systemically
      delivered therapeutic nanoparticles.
AB  - Antisense oligonucleotides (ASO) against specific molecular targets (e.g., Bcl-2
      and Raf-1) are important reagents in cancer biology and therapy. Phosphorothioate
      modification of the ASO backbone has resulted in an increased stability of ASO in
      vivo without compromising, in general, their target selectivity. Although the
      power of antisense technology remains unsurpassed, dose-limiting side effects of
      modified ASO and inadequate penetration into the tumor tissue have necessitated
      further improvements in ASO chemistry and delivery systems. Oligonucleotide
      delivery systems may increase stability of the unmodified or minimally modified
      ASO in plasma, enhance uptake of ASO by tumor tissue, and offer an improved
      therapy response. Here, we provide an overview of ASO design and in vivo delivery
      systems, and focus on preclinical validation of a liposomal nanoparticle
      containing minimally modified raf antisense oligodeoxynucleotide (LErafAON).
      Intact rafAON (15-mer) is present in plasma and in normal and tumor tissues of
      athymic mice systemically treated with LErafAON. Raf-1 expression is decreased in
      normal and tumor tissues of LErafAON-treated mice. Therapeutic benefit of a
      combination of LErafAON and radiation or an anticancer drug exceeds radiation or
      drug alone against human prostate, breast, and pancreatic tumors grown in athymic
      mice. Further improvements in ASO chemistry and nanoparticles are promising
      avenues in antisense therapy of cancer.

PMID- 17172712
TI  - Nucleic acid-based aptamers as promising therapeutics in neoplastic diseases.
AB  - Isolated through combinatorial libraries by an iterative in vitro selection
      process, small single-stranded nucleic acid compounds, named aptamers, have been
      developed as high-affinity ligands for a variety of targets, ranging from small
      chemical compounds to large proteins. In the last years, an increasing number of
      aptamers has been generated that represent potential antagonists of the disease
      associated target proteins. These molecules have been shown to discriminate
      between even closely related targets, thus representing a valid alternative to
      antibodies or other biomimetic receptors for the development of biosensors and
      other bioanalytical methods. Moreover, they can be easily stabilized by chemical
      modifications for in vivo applications and numerous examples have shown that
      stabilized aptamers against extracellular targets such as growth factors,
      receptors, hormones, or coagulation factors are very effective inhibitors of the
      corresponding protein function, thus resulting as useful reagents for target
      validation in a variety of diseases, including cancer. Indeed, many signaling
      proteins involved in diverse functions such as cell growth and differentiation
      can act as oncogenes and cause cellular transformation, thus making these high
      affinity ligands promising tools for cancer diagnosis or therapy.

PMID- 17172713
TI  - Guidelines for the selection of effective short-interfering RNA sequences for
      functional genomics.
AB  - To avoid long-double-stranded-RNA-dependent interferon response, short
      interfering RNAs (siRNAs) are widely used for RNA interference (RNAi) in
      mammalian cells. siRNA-based RNAi, however, may not be readily available for the
      large-scale gene silencing essential for systematic functional genomics, because
      only a limited fraction of siRNAs is capable of inducing effective mammalian
      RNAi. siRNAs correctly designed for the knockdown of a particular gene may also
      destroy the functions of unrelated genes. Here, we describe algorithms by which
      these serious setbacks can be eliminated in mammalian functional genomics using
      RNAi and a Web-based online software system for computing highly functional siRNA
      sequences with maximal target-specificity in mammalian RNAi.

PMID- 17172714
TI  - Suppression of apoptosis in the liver by systemic and local delivery of small
      interfering RNAs.
AB  - RNA interference (RNAi) is a sequence-specific gene-silencing mechanism triggered
      by double-stranded RNA. RNAi was shown to allow transient or stable knockdown of
      gene expression in a broad range of species and has been used successfully for
      functional genomic screens in mammalian cells and Caenorhabditis elegans.
      Standard therapeutic use of RNAi in clinical settings in humans has been hampered
      by the lack of effective methods to deliver the small-interfering RNAs (siRNAs)
      or short-hairpin RNA expression vectors into the diseased organs. In mice,
      systemic delivery of siRNAs by hydrodynamic intravascular injection leads to
      highly efficient uptake of siRNAs into the liver. Several groups demonstrated
      therapeutic use of RNAi in mouse models of acute liver failure or hepatitis B
      virus replication. This chapter will focus on the technical background of
      hydrodynamic and portal vein delivery techniques in mice and will give practical
      guidance for using these techniques for siRNA delivery into the liver.

PMID- 17172715
TI  - Target validation using RNA interference in solid tumors.
AB  - Reverse genetics is one strategy that is currently used to establish a link
      between a target gene and a disease phenotype. In this process, the function of a
      gene is inhibited and the consequence of its loss on a desired biological
      function, such as tumor growth and metastasis, is monitored. RNA interference
      (RNAi) has been found to be the most effective method to specifically inhibit
      gene expression. Notably, interactions between cancer cells, stromal cells, and
      the extracellular matrix (ECM) are crucial to angiogenesis and tumorigenesis.
      Tumor cells and the surrounding stroma are the principle source of growth factors
      and cytokines, which induce remodeling of the ECM mediated by metalloproteases
      (MMPs) secreted by macrophages. The production of macrophages is regulated by
      colony-stimulating factor (CSF)-1, which is overexpressed in several tumors. When
      short-interfering RNAs (siRNAs) targeting either the CSF-1 or its receptors were
      delivered into colon and breast cancer xenografts in mice, tumor growth was
      inhibited. Associated with this suppression, we observed decreased tumor
      vascularity, reduced expression of angiogenic factors and MMPs, and decreased
      macrophage recruitment to the tumors. The suppression of CSF-1 by RNA
      interference is therefore a powerful tool to block gene function and influence
      tumor-stroma interactions in solid tumor development.

PMID- 17172716
TI  - Validation of telomerase and survivin as anticancer therapeutic targets using
      ribozymes and small-interfering RNAs.
AB  - In recent years expanding knowledge about basic biology and a detailed
      understanding of the molecular pathways involved in tumor cell growth and
      progression have allowed the identification of numerous genes as potential
      therapeutic targets. Studies in which the expression of these genes was
      manipulated by antisense strategies have provided clues as to how we can
      intervene to specifically kill tumor cells or sensitize them to conventional
      chemical and physical antitumor therapies. Such tumor specificity can only be
      obtained by exploiting a basic difference between normal and malignant cells. In
      this context, targeting cytoprotective factors such as telomerase and survivin is
      particularly attractive because of their almost selective expression in tumor
      cells and their proven association with disease progression. This chapter
      summarizes the results obtained with ribozymes and small-interfering RNAs in the
      functional validation of these two targets in cell cultures and animal tumor
      models.

PMID- 17172717
TI  - Collagen-induced arthritis in mice: a major role for tumor necrosis factor-alpha.
AB  - Collagen-induced arthritis is the most widely used animal model for the
      evaluation of novel therapeutic strategies for rheumatoid arthritis. The disease
      is induced by immunization of genetically susceptible strains of mice or rats
      with type II collagen in adjuvant. Susceptibility to collagen-induced arthritis
      is associated with major histocompatibility complex (MHC) class II genes,
      although non-MHC genes also play a role. Both B- and T-lymphocytes are important
      in the pathogenesis of collagen-induced arthritis, with the peak of the T-cell
      response occurring around the time of disease onset. Histopathological assessment
      of the joints of animals with collagen-induced arthritis reveal a proliferative
      synovitis with infiltration of polymorphonuclear and mononuclear cells, the
      formation of an erosive pannus, cartilage degradation, and fibrosis. As in human
      rheumatoid arthritis, a number of both pro- and anti-inflammatory cytokines are
      expressed in the joints of mice with collagen-induced arthritis, including tumor
      necrosis factor-alpha (TNFalpha) and interleukin (IL)-1beta, IL-6, IL-1Ra, IL-10,
      and transforming growth factor beta. The use transgenic and knockout strains of
      mice, as well as biological inhibitors, have revealed important pathological
      roles for multiple cytokines. Of these, TNFalpha emerged as a valid therapeutic
      target for rheumatoid arthritis and this led to the setting up of clinical trials
      of anti-TNFalpha antibody therapy. Three anti-TNFalpha biologics(infliximab,
      etanercept, and adalimumab) are now approved for use and TNFalpha blockade
      therefore represents an important advance in our ability to treat rheumatoid
      arthritis.

PMID- 17172718
TI  - Novel opportunities for therapeutic targeting in systemic autoimmune diseases.
AB  - Systemic autoimmune diseases, such as systemic lupus erythematosus and rheumatoid
      arthritis, continue to cause significant morbidity in affected persons. In the
      past few years, significant progress was made in understanding their pathogenesis
      and the underlying molecular mechanisms. As a result, a number of new exciting
      therapeutic options have become available, and novel therapeutic targets have
      emerged, including B-cell depletion therapies, B cell-activating factor of tumor
      necrosis factor family (BAFF) antagonists, and FcgammaRIIB receptor antagonists.
      Also promising is the current interest centered on the development of inhibition
      of signal transduction pathways, such as pharmacological inhibitors that act at
      various levels of signal transduction pathways.

PMID- 17172719
TI  - Considerations for target validation and industrial approaches.
AB  - Target validation in health and disease integrates the modulation of a certain
      molecular target with an expected biological/biochemical/physiological or
      pathophysiological response or effect. The current state-of-the-art in target
      validation requires the interface of multiple complementary approaches and
      technologies to define the mechanistic connectivity between a molecular target
      and underlying micro- and macrobiotic processes. Target validation also
      represents the basis for "drug target validation" with focus on therapeutic
      applications. The concepts of "target validation" and "drug-based therapeutic
      intervention" continue to coevolve as new classes of therapeutic agents and
      delivery systems emerge and enable us to target or modulate previously
      inaccessible molecular entities.

PMID- 17172721
TI  - Treatment options and individualized medicine.
AB  - Although several drug targets are identified, current strategies in therapy do
      not take into account that patients vary in their response to drugs, both with
      respect to efficacy and toxic side effects. Whereas both clinical and
      histopathologic predictors of prognosis are established in some diseases, a
      better understanding of the molecular mechanisms that determine treatment
      response should play an important role in the development of individualized
      medicine. Treatment optimization will rely on the ability to adjust treatment
      algorithms for use in the individual patient based on the identification and
      validation of the factors that critically determine treatment outcomes, including
      diagnosis, disease phase and characteristics, organ functions, age, and gender.
      Although the analysis of a single genetic marker (e.g., CYP polymorphisms) may
      yield significant information that predicts drug response, the prediction
      obtained from the analysis of several genetic and epigenetic markers is
      potentially more powerful in selecting patients for effective therapy, whereas
      sparing those who would not respond or would suffer undesirable side effects. In
      this chapter, several relevant examples are presented.

PMID- 17172720
TI  - Regulatory RNAs: future perspectives in diagnosis, prognosis, and individualized
      therapy.
AB  - With potentially up to 1000 microRNAs (miRNAs) present in the human genome,
      altogether regulating the expression of thousands of genes, one can anticipate
      that miRNAs will play a significant role in health and disease. Deregulated
      protein expression induced by a dysfunctional miRNA-based regulatory system is
      thus expected to lead to the development of serious, if not lethal, genetic
      diseases. A relationship among miRNAs, Dicer, and cancer has recently been
      suggested. Further investigations will help establish specific causal links
      between dysfunctional miRNAs and diseases. miRNAs of foreign origin, e.g.,
      viruses, may also be used as specific markers of viral infections. In these
      cases, miRNA expression profiles could represent a powerful diagnostic tool.
      Regulatory RNAs may also have therapeutic applications, by which disease-causing
      genes or viral miRNAs could be neutralized, or functional miRNAs be restored.
      Will bedside miRNA expression profiling eventually assist physicians in providing
      patients with accurate diagnosis, personalized therapy, and treatment outcome?

PMID- 17172722
TI  - Main approaches to target discovery and validation.
AB  - The identification and validation of disease-causing target genes is an essential
      first step in drug discovery and development. Genomics and proteomics
      technologies have already begun to uncover novel functional pathways and
      therapeutic targets in several human diseases such as cancers and autoimmunity.
      Also, bioinformatics approaches have highlighted several key targets and
      functional networks. In contrast to gene-profiling approaches, phenotype-oriented
      target identification allows direct link between the genetic alterations and a
      disease phenotype. Therefore, identified genes are more likely to be a cause
      rather than a consequence of the disease. Once a gene target or a mechanistic
      pathway is identified, the next step is to demonstrate that it does play a
      critical role in disease initiation, perpetuation, or both. A range of strategies
      exists for modulating gene expression in vitro and in vivo. These strategies
      include the use of antibodies, negative dominant controls, antisense
      oligonucleotides, ribozymes, and small-interfering RNAs. In contrast to in vitro
      assays, mouse reverse genetics such as knockout phenotypes has become a powerful
      approach for deciphering gene function and target validation in the context of
      mammalian physiology. In addition to disease-causing genes, the identification of
      antigens that stimulate both arms of the immune system is the major goal for
      effective vaccine development. The hope is that target discovery and validation
      processes will concurrently identify and validate therapeutic targets for drug
      intervention in human diseases.

PMID- 17172723
TI  - Bioinformatics approaches to cancer gene discovery.
AB  - The Cancer Gene Anatomy Project (CGAP) database of the National Cancer Institute
      has thousands of known and novel expressed sequence tags (ESTs). These ESTs,
      derived from diverse normal and tumor cDNA libraries, offer an attractive
      starting point for cancer gene discovery. Data-mining the CGAP database led to
      the identification of ESTs that were predicted to be specific to select solid
      tumors. Two genes from these efforts were taken to proof of concept for
      diagnostic and therapeutics indications of cancer. Microarray technology was used
      in conjunction with bioinformatics to understand the mechanism of one of the
      targets discovered. These efforts provide an example of gene discovery by using
      bioinformatics approaches. The strengths and weaknesses of this approach are
      discussed in this review.

PMID- 17172724
TI  - Analysis of gene networks for drug target discovery and validation.
AB  - Understanding responses of the cellular system for a dosing molecule is one of
      the most important problems in pharmacogenomics. In this chapter, we describe
      computational methods for identifying and validating drug target genes based on
      the gene networks estimated from microarray gene expression data. We use two
      types of microarray gene expression data: gene disruptant microarray data and
      time-course drug response microarray data. For this purpose, the information of
      gene networks plays an essential role and is unattainable from clustering
      methods, which are the standard for gene expression analysis. The gene network is
      estimated from disruptant microarray data by the Bayesian network model, and then
      the proposed method automatically identifies sets of genes or gene regulatory
      pathways affected by the drug. We use an actual example from analysis of
      Saccharomyces cerevisiae gene expression profile data to express a concrete
      strategy for the application of gene network information toward drug target
      discovery.

PMID- 17172726
TI  - Molecular classification of breast tumors: toward improved diagnostics and
      treatments.
AB  - Recent advances in gene expression profiling and other "omics" technologies have
      revolutionized cancer research and hold the potential of also revolutionizing
      clinical practice. These high-throughout approaches have radically changed our
      ability to study cells and tissues in a more comprehensive way. Combined with
      advanced bioinformatics and the possibility to simulate biological processes in
      computers, this field of "systems biology" allows us to study the organism as a
      whole entity. This chapter describes the molecular classification and
      characterization of breast tumors into distinct subtypes by using DNA microarrays
      and discusses the statistical relationships of the subgroups with clinical
      features of the disease.

PMID- 17172725
TI  - Target discovery and validation in pancreatic cancer.
AB  - Pancreatic cancer is a lethal disease and rational strategies for early detection
      and targeted therapies are urgently required to alleviate the dismal prognosis of
      this neoplasm. The use of global RNA and protein expression-profiling
      technologies, such as DNA microarrays, serial analysis of gene expression, and
      mass spectrometric analysis of proteins, have led to identification of cellular
      targets with considerable potential for clinical application and patient care.
      These studies underscore the importance of pursuing large-scale profiling of
      human cancers not only for furthering our understanding of the pathogenesis of
      these malignancies but also for developing strategies to improve patient
      outcomes.

PMID- 17172727
TI  - Discovery of differentially expressed genes: technical considerations.
AB  - Identification and characterization of differentially expressed genes may be an
      important first step toward the understanding of both normal physiology and
      disease. A multitude of techniques belonging to two main categories have been
      developed to identify the differences in gene expression between samples from
      different biological origin: selection techniques and global techniques. Whereas
      the selection techniques strive to identify specific differentially expressed
      genes, the global techniques analyze the total transcriptome or a major part of
      the RNA population in a defined biological material. By exploiting the known
      sequences of the adaptors used in suppressive subtraction hybridization
      technique, a strategy named novel rescue-suppression-subtractive hybridization
      was developed. It should facilitate the discovery of differentially expressed
      genes.

PMID- 17172728
TI  - Genome-wide sreening by using small-interfering RNA expression libraries.
AB  - RNA interference (RNAi) is an evolutionarily conserved phenomenon in which gene
      expression is silenced by double-stranded RNA (dsRNA) in a sequence-specific
      manner. This technology has the potential to affect all aspects of target
      discovery and validation. With the completion of the human genome, it is now
      possible to design small-interfering RNA (siRNA) libraries targeting every human
      gene. Specific siRNAs, libraries containing a pathway, gene family, or gene set
      of interest, are expected to unsecure new targets in pathways of therapeutic
      interest. Here, we highlight the potential of siRNA screens for target
      identification by using cell-based assays.

PMID- 17172729
TI  - Hammerhead ribozyme-based target discovery.
AB  - With the accumulation of vast amounts of data as a result of the sequencing of
      the human genome, it is necessary to identify human genes that are involved in
      various cellular, developmental, and disease-related processes and to clarify
      their functions and potential utility as targets in the treatment of disease.
      Identification methods based on the use of hammerhead and hairpin ribozymes have
      received increasing attention as possible tools for the rapid identification of
      key genes involved in biological processes. This chapter describes the method
      known as gene-discovery by a hammerhead ribozyme library for elucidation of the
      gene function. Use of this technology has already revealed new insights into
      several important biological phenomena.

PMID- 17172730
TI  - Production of siRNA- and cDNA-transfected cell arrays on noncoated chambered
      coverglass for high-content screening microscopy in living cells.
AB  - In this chapter, we provide a protocol for the production of transfected cell
      arrays in living mammalian cells on noncoated chambered coverglass for the
      systematic functional analyses of human genes by high-content screening
      microscopy. This method should facilitate drug target validation by small
      interfering RNAs.

PMID- 17172731
TI  - Transgenic animal models in biomedical research.
AB  - Transgenic animals have become a key tool in functional genomics to generate
      models for human diseases and validate new drugs. Transgenesis includes the
      addition of foreign genetic information to animals and specific inhibition of
      endogenous gene expression. Recently, animal models provided novel insight and
      significantly improved our understanding of the initiation and perpetuation of
      human diseases. Moreover, they are an invaluable tool for target discovery,
      validation, and production of therapeutic proteins. However, despite the
      generation of several transgenic and knockout models, obtaining relevant models
      still faces several theoretical and technical challenges. Indeed, genes of
      interest are not always available and gene addition or inactivation sometimes
      does not allow clear conclusions because of the intrinsic complexity of living
      organisms or the redundancy of some metabolic pathways. In addition to homologous
      recombination, endogenous gene expression can be specifically inhibited using
      several mechanisms such as RNA interference. Here, some animal models are
      described to illustrate their importance in biomedical research. Moreover,
      guidelines for generation of these animals are presented.

PMID- 17172732
TI  - Keratin transgenic and knockout mice: functional analysis and validation of
      disease-causing mutations.
AB  - The intermediate filament (IF) cytoskeleton of mammalian epithelia is generated
      from pairs of type I and type II keratins that are encoded by two large gene
      families, made up of 54 genes in humans and the mouse. These genes are expressed
      in a spatiotemporal and tissue-specific manner from the blastocyst stage onward.
      Since the discovery of keratin mutations leading to epidermolysis bullosa
      simplex, mutations in at least 18 keratin genes have been identified that result
      in keratinopathies of the epidermis and its appendages. Recently, noncanonical
      mutations in simple epithelial keratins were associated with pancreatic, liver,
      and intestinal disorders, demonstrating that keratins protect epithelia against
      mechanical and other forms of stress. In recent years, animal models provided
      novel insight and significantly improved understanding of IF function in tissue
      homeostasis and its role in disease. Pathological phenotypes detected in mutant
      mice generated so far range from embryonic lethality to tissue fragility to
      subtlety, which often depends on their genetic background. This range implies at
      least a partial influence of yet unidentified modifier genes on the phenotype
      after the ablation of the respective keratin. To date, nearly all available
      keratin mouse models were generated by taking advantage of conventional gene
      targeting strategies. To reveal their cell type-specific functions and the
      mechanisms by which mutations lead to disease, it will be necessary to use
      conditional gene-targeting strategies and the introduction of point-mutated gene
      copies. Furthermore, conditional strategies offer the possibility to overcome
      embryonic or neonatal lethality in some of the keratin-deficient mice.

PMID- 17172733
TI  - The HUVEC/Matrigel assay: an in vivo assay of human angiogenesis suitable for
      drug validation.
AB  - The future ability to manipulate the growth of new blood vessels (angiogenesis)
      holds great promise for treating ischemic disease and cancer. Several models of
      human in vivo angiogenesis have been described, but they seem to depend on
      transgenic support and have not been validated in a therapeutic context. Here, we
      describe an in vivo assay that mimics human angiogenesis in which native human
      umbilical vein-derived endothelial cells are suspended in a liquid
      laminin/collagen gel (Matrigel), injected into immunodeficient mice, and develop
      into mature, functional vessels that vascularize the Matrigel plug in the course
      of 30 d. Moreover, we demonstrate how to target this process therapeutically by
      sustained delivery of the angiogenesis inhibitor endostatin from subcutaneously
      implanted microosmotic pumps.

PMID- 17172734
TI  - A murine model for studying hematopoiesis and immunity in heart failure.
AB  - Recent epidemiological research indicates that a coexistent anemia among patients
      with heart failure might worsen their prognosis. However, whether the reduced
      synthesis of red blood cells is a contributing factor to the development and
      progression to overt heart failure, or whether it simply is a mere consequence of
      a dysfunctional heart, remains to be elucidated. Studies in mice with
      experimentally induced acute myocardial infarction leading to subsequent
      development of a postinfarction congestive heart failure have shed some light on
      this problem. Careful analyses of the number and of the functions of various
      hematopoietic cells residing in either blood or bone marrow point to a possible
      inhibitory role of cytokines, such tumor necrosis factor alpha, on hematopoiesis.
      The present protocols will hopefully encourage further studies of hematopoiesis
      and immunity in heart failure by using a combination of animal models with state
      of-the-art techniques in molecular biology to define and validate possible
      targets for therapy.

PMID- 17172735
TI  - An overview of the immune system and technical advances in tumor antigen
      discovery and validation.
AB  - The ability of the immune system to distinguish between self- and nonself
      antigens is controlled by mechanisms of central and peripheral tolerance.
      Although the induction and maintenance of tolerance is important for preventing
      autoimmunity, breaking self-tolerance is a crucial constituent for combating
      cancers. Cancer patients are able to develop spontaneous immune responses to
      tumors that they bear, however these responses are not suboptimal for eradicating
      tumors. Moreover, none of the current immune strategies is able to activate the
      immune system to respond against tumor cells as it responds against infectious
      agents. These observations have raised the question of how to activate immunity
      in cancer patients to a threshold required for tumor rejection. Because tolerance
      is emerging as a central obstacle for immune recognition of human tumor antigens,
      this chapter describes how T- and B-cells are generated and activated in the
      periphery. It also outlines the technical advances in tumor antigen discovery and
      validation.

PMID- 17172736
TI  - Potential target antigens for immunotherapy identified by serological expression
      cloning (SEREX).
AB  - Immunotherapy in cancer relies on the identification and characterization of
      potential target antigens that can be recognized by effector cells of the immune
      system. Several strategies have been developed to identify such antigens, which
      then can be used for immunization strategies. Serological analysis of recombinant
      tumor cDN expression libraries (SEREX) identifies tumor antigens based on a
      spontaneous humoral immune response in cancer patients. SEREX is not limited to
      tumor types that can be grown in cell culture nor does it depend on T-cell clones
      that recognize the autologous tumor. SEREX-defined antigens need to be evaluated
      following an algorithm of several analytical steps before they become new target
      antigens for active immunotherapy: expression analysis to evaluate tumor
      association, serological analysis with sera from tumor patients and normal
      individuals to prove tumor-associated immunogenicity, identification of potential
      peptide epitopes for CD8 and CD4 T-cells, and evaluation in T-cell assays to
      demonstrate their potential use as vaccine targets. We recently identified a new
      breast cancer differentiation antigen designated as NY-BR-1 in an autologous
      breast cancer SEREX screening. The different steps of further evaluation are
      summarized in this chapter.

PMID- 17172737
TI  - Identification of tumor antigens by using proteomics.
AB  - The recent progress of proteomics has opened new avenues for tumor-associated
      antigen discovery. Here, I describe a two-dimensional (2D), gel-based Western
      blot approach for screening and identification of proteins eliciting a humoral
      response in cancer. Sera from patients are used in 2D Western blot experiments
      for screening of autoantibodies, and the immunoreactive target proteins are
      subsequently identified by mass spectrometry. Applied to several types of cancer,
      this proteomic-based approach has revealed a high frequency of autoantibodies in
      sera from cancer patients and has led to the identification of novel tumor
      antigens. Relevant examples are described.

PMID- 17172738
TI  - Protein arrays: a versatile toolbox for target identification and monitoring of
      patient immune responses.
AB  - Functional proteomics is a promising technique for the rational identification of
      novel therapeutic targets and biological markers. The studies of protein-protein
      interactions have been gained from the development of high-throughput
      technologies such as the yeast two-hybrid system, protein arrays, phage display,
      and systematic analysis of interaction maps for the prediction of protein
      functions. Because antibodies are used extensively as diagnostic and clinical
      tools, the characterization of their antigen specificity is of prime importance.
      Indeed, screening protein arrays with sera from patients with either cancer or
      autoimmune diseases would facilitate the identification of autoantibody
      signatures that can be used for diagnosis and/or prognosis of patients. The
      usefulness of multiplexed measurements lies not only in the ability to screen
      many individual marker candidates but also in evaluating the use of multiple
      markers in combination. Here, we review the advantage of protein and serum
      screening of peptides and cDNA repertoires displayed on phages as well as the
      fabrication of protein microarrays for probing immune responses in patients.

PMID- 17172739
TI  - The use of protoplasts to study innate immune responses.
AB  - The use of plant protoplast transient expression system has facilitated the
      discovery and dissection of many signal transduction pathways in response to
      hormones, metabolites, and stresses. Recently, Arabidopsis protoplasts also have
      been used successfully to study plant innate immune responses triggered by
      pathogen-derived elicitors. Here, we describe the detailed protocols for studying
      innate immune responses, including cell death and early defense gene regulation
      activated by two types of elicitors, pathogen-associated molecular patterns and
      bacterial type III effectors in Arabidopsis protoplasts. This cell-based system
      simplifies the complex pathogen-plant interactions to pure individual signals and
      synchronized cell-autonomous responses. The application of this novel approach
      provides high temporal and spatial resolution to enhance our understanding of the
      distinct and overlapping signaling events in pathogen-associated molecular
      pattern- and bacterial type III effector-activated immune responses at the
      molecular and cellular level.

PMID- 17172740
TI  - Marker-exchange mutagenesis and complementation strategies for the Gram-negative
      bacteria Xanthomonas oryzae pv. oryzae.
AB  - This chapter describes methods for targeted knockouts using marker exchange
      mutagenesis and complementation of the Gram-negative bacteria Xanthomonas oryzae
      pv. oryzae. We have used these methods to demonstrate that type I secretion and
      modification systems are involved in avrXa21 activity of X. oryzae pv. oryzae.

PMID- 17172741
TI  - Whole-genome analysis to identify type III-secreted effectors.
AB  - Many Gram-negative plant and animal pathogens share a common virulence strategy
      that relies on the specialized type III secretion system. This apparatus is used
      to secrete virulence factors, called effectors, into the extracellular host
      environment and directly into the cytoplasm of host cells. Effectors interfere
      with host signaling and host metabolism to create an optimal environment for
      pathogen replication. The identification of effectors in plant pathogens was
      limited for many years to those effectors that elicit strong plant defenses on
      some hosts. The members of this subset, called avirulence proteins, can be
      readily identified because they dominantly confer strong defense-inducing
      properties to a heterologous virulent strain. This chapter describes two methods
      to identify type III-secreted effectors in plant pathogens independently of their
      phenotype. The first method consists of an in vivo molecular genetic screen that
      uses the activity of an avirulence protein to identify effectors without
      avirulence activity. It should be possible to apply this method to most Gram
      negative plant pathogens. The second method consists of a bioinformatic approach
      applicable to those pathogens for which at least a draft genome sequence is
      available.

PMID- 17172742
TI  - In planta expression of oomycete and fungal genes.
AB  - Large-scale genome sequencing projects have generated a wealth of sequence
      information for plant pathogenic microbes such as oomycetes and fungi. Functional
      genomic approaches are essential to exploit the sequence information to identify
      pathogen effector genes that trigger cellular and molecular responses in plant
      cells. This chapter describes two functional assays, agroinfiltration and
      agroinfection. These assays allow rapid functional expression of pathogen genes
      in plants and can be used in high-throughput screens.

PMID- 17172743
TI  - Use of Nipponbare BAC clones for physical mapping of an R gene locus in rice.
AB  - Major advances in rice genomics during the last few years have made positional
      cloning in rice much more efficient. Nipponbare is a model rice genotype being
      sequenced by the International Rice Genome Sequencing Project Consortium. Here,
      we describe an efficient procedure of the construction of physical map for
      positional cloning of resistance gene (R) using the Nipponbare genetic resources.
      This advanced strategy should be useful for the efficient identification of
      agronomic important R genes from many resistant rice genotypes, including wild
      rice species.

PMID- 17172744
TI  - Agrobacterium-mediated transformation to create an insertion library in
      Magnaporthe grisea.
AB  - Magnaporthe grisea is the causal agent of rice blast disease and represents a
      model organism for the study of fungal plant-pathogen interactions. Pathogenicity
      is a complex phenotype, which is carefully orchestrated by the fungus and begins
      with recognition and infection of the host plant, followed by growth within the
      plant cells, and finally dissemination to the next host and continuation of the
      fungal life cycle. Certain genes must condition the ability of a pathogenic
      fungus to infect and cause disease symptoms. To learn more about the infection
      process and the genes that are involved in the complex interplay between M.
      grisea and rice, we used an insertional mutagenesis approach to attempt to
      randomly disrupt all genes in the fungal genome. Two transformation approaches
      were used to build a library of insertion strains in M. grisea. Polyethylene
      glycol/CaCl2-mediated protoplast transformation was the initial method we used
      and resulted in the generation of just more than 17,000 insertion strain lines.
      Later Agrobacterium tumefaciens-mediated transformation was adopted and the final
      number of insertional mutant strains of M. grisea strain 70-15 generated was more
      than 57,000. Here, we describe the methods used for A. tumefaciens-mediated
      transformation of M. grisea and the optimized protocols we have developed to
      enable high-throughput fungal transformation.

PMID- 17172745
TI  - Identification of components in disease-resistance signaling in Arabidopsis by
      map-based cloning.
AB  - With the whole genome sequence and thousands of defined polymorphisms between
      ecotypes available, it has become much easier to clone a gene by position (map
      based cloning) in Arabidopsis. Recent development of DNA-isolation methods in
      plants also dramatically facilitated large-scale processing of DNA samples. Here,
      we describe detailed protocols for each step on general scheme of map-based
      cloning, from mutagenesis to genetic analysis, from rough mapping to fine
      mapping, and at the end to cloning the gene. Not only can these methods be used
      to isolate genes that are involved in plant innate immunity, they can also be
      adapted for any forward genetics projects in Arabidopsis.

PMID- 17172746
TI  - Yeast two-hybrid approaches to dissecting the plant defense response.
AB  - We describe a reliable GAL4-based yeast two-hybrid system for identifying and
      isolating clones encoding proteins interacting with a protein of interest. This
      two-hybrid system gives extremely low background and few false-positive clones,
      making it ideal for library screening purposes. We have successfully used it not
      only to isolate Arabidopsis NPR1-interactors from rice but also to pull out the
      rice NPR1 ortholog using one of the interactors as bait.

PMID- 17172747
TI  - Use of rolling-circle amplification for large-scale yeast two-hybrid analyses.
AB  - Detection of protein-protein interactions on a large-scale has become a major
      focus of functional genomics after the completion of genome sequencing. The
      information generated from these studies not only assembles proteins into
      signaling networks, but also reveals potential functions of uncharacterized
      proteins when their interacting partners have known functions. We have developed
      a rolling circle amplification-based yeast two-hybrid scheme that allows one to
      test reproducibility and specificity of the interactions on a large scale. Using
      this scheme, technical false-positives from yeast two-hybrid analyses can be
      efficiently minimized.

PMID- 17172748
TI  - Preparative denaturing isoelectric focusing for enhancing sensitivity of
      proteomic studies.
AB  - Substantial evidence implicates important roles for both protein phosphorylation
      and protein degradation in regulation of plant defense responses. Therefore,
      interest is growing in applying proteomics techniques to investigate these
      posttranscriptional changes. We have found, however, that most proteins of
      interest are not visible on two-dimensional (2D) gels without previous
      prefractionation. This chapter describes the use of preparative denaturing
      isoelectric focusing to enrich for proteins of specific isoelectric points before
      separation by 2D gels. This method significantly increases the sensitivity of 2D
      gel-based comparisons.

PMID- 17172750
TI  - Use of microarray analysis to dissect the plant defense response.
AB  - Microarray analysis is a technology that allows simultaneous measurement of the
      messenger RNA levels of thousands of genes. There are several different
      technology platforms in use, including oligo arrays synthesized directly on the
      underlying substrate, and spotted arrays produced by applying oligonucleotides or
      other nucleic acids to glass slides. The advantages of various platforms are
      discussed. Analysis of the large data sets produced from microarray experiments
      requires the application of statistical methods to define significant differences
      in gene expression, and computerized algorithms for pattern recognition. Early
      applications of microarray analysis to studies of disease resistance have led to
      recognition of the large numbers of genes that respond to infection, insights
      into the nature of gene-for-gene resistance, efforts to model the topology of the
      signaling network controlling inducible defense responses, and identification of
      promoter elements associated with particular expression patterns.

PMID- 17172749
TI  - Use of massively parallel signature sequencing to study genes expressed during
      the plant defense response.
AB  - Massively parallel signature sequencing is a sequencing-based method that
      provides quantitative gene expression data for nearly all transcripts in a
      particular ribonucleic acid sample. Although the sequencing technology is
      practiced as a service by a California-based company, we have developed methods
      for the handling and analysis of these data. This chapter describes the steps
      involved in obtaining data from massively parallel signature sequencing, aligning
      the signatures to genomic sequence, identifying novel transcripts, and performing
      quantitative analyses of genes expressed under conditions such as disease
      treatments.

PMID- 17172751
TI  - Use of robust-long serial analysis of gene expression to identify novel fungal
      and plant genes involved in host-pathogen interactions.
AB  - Identification of important transcripts from fungal pathogens and host plants is
      indispensable for full understanding the molecular events occurring during fungal
      plant interactions. Recently, we developed an improved LongSAGE method called
      robust-long serial analysis of gene expression (RL-SAGE) for deep transcriptome
      analysis of fungal and plant genomes. Using this method, we made 10 RL-SAGE
      libraries from two plant species (Oryza sativa and Zea maize) and one fungal
      pathogen (Magnaporthe grisea). Many of the transcripts identified from these
      libraries were novel in comparison with their corresponding EST collections.
      Bioinformatic tools and databases for analyzing the RL-SAGE data were developed.
      Our results demonstrate that RL-SAGE is an effective approach for large-scale
      identification of expressed genes in fungal and plant genomes.

PMID- 17172752
TI  - Analysis of gene function in rice through virus-induced gene silencing.
AB  - Virus-induced gene silencing (VIGS) is a powerful RNA-silencing based technology
      adapted for the study of host-gene function. VIGS functions through the
      expression of a host gene from a virus vector. Both the virus-encoded host
      sequence and the homologous host target messenger RNA are destroyed or made
      inactive through a host surveillance system. Here, we describe procedures for the
      use of a new virus vector for VIGS in monocotyledonous hosts and, in particular,
      in rice (Oryza sativa), a species for which no VIGS vector was previously
      available.

PMID- 17172753
TI  - Use of RNA interference to dissect defense-signaling pathways in rice.
AB  - The RNA interference (RNAi) technique is a powerful tool to suppress gene
      expression and has been widely used for functional discovery of eukaryotic genes.
      To dissect defense-signaling pathways in rice, it is important to generate a
      series of rice mutant lines deficient in or insensitive to major signal molecules
      such as jasmonic acid and ethylene. Here we describe an RNAi protocol for
      generating and characterizing transgenic gene-silencing lines defective in rice
      jasmonic acid signaling. The RNAi technique should be useful for effective
      suppression of host genes encoding signaling components and facilitating the
      dissection of defense signal pathways in rice.

PMID- 17172754
TI  - Virus-induced gene silencing in plant roots.
AB  - Virus-induced gene silencing (VIGS) has been used as a quick and easy tool to
      assess gene function in plants. The virus, carrying a portion of an endogenous
      gene, triggers a homology-based defense mechanism when introduced into plants.
      Infection with the modified virus results in gene-specific transcript
      degradation. Several virus-based vectors have been developed for use in VIGS. One
      of these virus vectors, tobacco rattle virus (TRV), has a large host range and is
      transmitted by phytopathogenic nematodes of the genera Trichodorus and
      Paratrichodorus. TRV has been used in VIGS to study gene function in above-ground
      parts of plants. This chapter describes a protocol for the use of TRV vector to
      silence genes in roots.

PMID- 17172755
TI  - Methods for engineering resistance to plant viruses.
AB  - The development of genetically engineered resistance to plant viruses is a result
      of efforts to understand the plant-virus interactions involved in
      "crossprotection," a phenomenon observed with several plant virus diseases.
      Historically, expression of the coat protein gene of Tobacco mosaic virus in
      transgenic tobacco (Nicotiana tabacum) plants is the first example of transgene
      mediated resistance to a plant virus. Subsequently, virus-derived sequences of
      several plant viruses were shown to confer virus resistance in experimental
      and/or natural hosts. For plant RNA viruses, virus complementary DNA sequences
      shown to confer resistance include wild-type genes, mutated genes that produced
      truncated protein products, and nontranslatable sense or antisense transcripts to
      various regions of the virus genome. Resistance also has been demonstrated for
      some viruses by mutant trans-dominant gene products, derived from the movement
      protein and replication-associated protein genes. In addition to virus-derived
      sequences, gene sequences of plant origin have also been used for transgenic
      resistance, and such resistance can be virus-specific, for instance, R genes
      isolated from resistant plant genotypes, or nonspecific, for example, ribosome
      inactivating proteins and proteinase inhibitors. Plantibodies and 2-5A
      synthetase, a class of proteins of mammalian origin, have also been useful in
      engineering plant virus resistance. In the case of transgenic resistance mediated
      by viral coat protein, the mechanism of resistance was suggested to operate
      during the early events of virus infection. However, transgene-mediated RNA
      silencing and generation of small interfering RNAs appears to be the primary
      mechanism that confers resistance to plant viruses. Despite the advantages of
      transgene-mediated resistance, current interest in the development and use of
      transgenic virus resistant plants is low in most parts of the world. However,
      because of its real potential, we believe that this technology will have more
      widespread and renewed interest in the near future.

PMID- 17172756
TI  - Development of genetically engineered resistant papaya for papaya ringspot virus
      in a timely manner: a comprehensive and successful approach.
AB  - Papaya orchards throughout most of the world are severely damaged by the
      destructive disease caused by the papaya ringspot virus (PRSV). PRSV-resistant
      papaya expressing the coat protein gene (CP) of PRSV have been used in Hawaii to
      control PRSV since 1998. This chapter presents the experimental steps involved in
      the development of transgenic papaya, including transgene construction,
      transformation, and analysis for virus resistance of the transformed papaya. We
      also describe the important factors that enabled deregulation, commercialization,
      and adoption of transgenic papaya to occur in Hawaii in a timely manner. Transfer
      of this technology to other countries with the similar goal and the development
      of transgenic papaya in other regions of the world also are described.

PMID- 17172757
TI  - Cryocrystallography of macromolecules: practice and optimization.
AB  - Techniques for flash-cooling protein crystals to around 100K (-173 degrees C) for
      data collection have developed enormously in the last decade, to the extent that
      cryocrystallography is now standard practice. The main advantage of these methods
      is the vastly reduced rate of radiation damage to protein crystals in the X-ray
      beam at cryogenic temperatures over room temperature, extending their lifetimes
      so that complete datasets can be collected from a single crystal. The practical
      application of the techniques has become somewhat anecdotal and rather fixed
      within individual laboratories. This chapter gives step-by-step guidelines for
      flash-cooling crystals and some of the rationale for the recommended procedures.
      Optimization of the entire cryoprotocol can give substantial improvements to both
      the resolution and quality of the data, often resulting in more straight-forward
      structure solution and subsequent model refinement. Attention to seemingly
      insignificant details can have a real impact on the usefulness of the final
      dataset, and are thus worth addressing.

PMID- 17172758
TI  - Determination of reaction intermediate structures in heme proteins.
AB  - Developments in structural biology and molecular biology have allowed
      increasingly detailed investigations of structure-function relationships.
      Although atomic-resolution structures of proteins are becoming more common, a
      growing number of structural studies have focused on the role played by dynamics
      and have sought to determine the structure of intermediates in protein reactions.
      These experiments have revealed the first atomic-level pictures of enzyme
      catalysis and the conformational motions required for biological function. This
      chapter uses the cryotrapping of reaction intermediates in horse heart myoglobin
      (Mb) to illustrate the methods utilized in determining the structures of reaction
      intermediates in protein systems. The techniques described here are applicable to
      a wide variety of heme proteins including Mb, hemoglobin, photosynthetic reaction
      centers, and cytochrome p450cam.

PMID- 17172759
TI  - Annealing macromolecular crystals.
AB  - The process of crystal annealing has been used to improve the quality of
      diffraction from crystals that would otherwise be discarded for displaying
      unsatisfactory diffraction after flash cooling. Although techniques and protocols
      vary, macromolecular crystals are annealed by warming the flash-cooled crystal,
      then flash cooling it again. To apply macromolecular crystal annealing, a flash
      cooled crystal displaying unacceptably high mosaicity or diffraction from ice is
      removed from the goniometer and immediately placed in cryoprotectant buffer. The
      crystal is incubated in the buffer at either room temperature or the temperature
      at which the crystal was grown. After about 3 min, the crystal is remounted in
      the loop and flash cooled. In situ annealing techniques, where the cold stream is
      diverted and the crystal allowed to warm on the loop prior to flash cooling, are
      variations of annealing that appears to work best when large solvent channels are
      not present in the crystal lattice or the solvent content of the crystal is
      relatively low.

PMID- 17172760
TI  - First analysis of macromolecular crystals: biochemistry and x-ray diffraction.
AB  - Methods are described for performing a first analysis of newly prepared
      macromolecular crystals. Biochemical analysis using denaturing gel
      electrophoresis on dissolved crystals informs on the content of the crystal.
      Detailed protocols are given for mounting crystals in capillaries or fiber loops
      in preparation for analysis of their X-ray diffractive properties.

PMID- 17172761
TI  - X-ray data collection from macromolecular crystals.
AB  - Instruments, methods, and software for modern macromolecular crystallography is
      becoming so effective that molecular biologists often can solve structures from
      their crystals by working "without a license." In this chapter, the authors
      attempt to demystify some of the apparatus and techniques by providing a roadmap.
      Current methods for collecting X-ray diffraction data from macromolecular
      crystals are described. The principles of operation of the required X-ray
      sources, optics, goniometers, and detectors are outlined, and a typical data
      collection protocol is presented. Optimization of data quality is a pivotal stage
      in the whole crystallographic process, so much attention is given to the detailed
      setting up of the experiment. This is followed by a summary of the basic ideas
      behind the diffraction image-processing packages and their application to data
      reduction. Despite the increasingly "black box" nature of these computer
      programs, understanding how they extract the intensities, errors, and indices
      from the data can make subsequent structure solution and refinement much easier.

PMID- 17172762
TI  - Characterizing a crystal from an initial native dataset.
AB  - Methods are presented for characterizing a crystal given an initial X-ray
      diffraction dataset. These methods can facilitate the structure determination
      process and illuminate the oligomeric state and symmetry of your molecule before
      the crystal structure is determined. Specifically, these methods include (1)
      calculation of Matthews coefficient to estimate the number of molecules in the
      asymmetric unit; (2) calculation and interpretation of a self-rotation function
      to evaluate the point group symmetry of the crystallized oligomer, if contained
      in the crystal; (3) calculation and interpretation of a native Patterson map to
      evaluate the presence of noncrystallographic translational symmetry; and (4)
      calculation of statistics to evaluate the possibility of merohedral twinning in a
      crystal.

PMID- 17172763
TI  - Molecular replacement.
AB  - As more protein structures are solved, the likelihood that current structural
      investigations will involve proteins for which there exists no homologous
      structure continually decreases. The extraction of phase information from
      diffraction experiments is one of several great barriers that crystallographers
      must overcome on the path to structure solution. One means to overcome this
      obstacle, the technique of molecular replacement, uses the structural similarity
      between proteins with similar sequences to give a good first estimate of the
      phases for the diffraction data of the protein of interest. The programs that
      execute this technique currently come in many flavors, from traditional Patterson
      based methods, to stochastic searches in greater than three dimensions, to
      maximum likelihood-enhanced molecular replacement, each possessing unique
      advantages that can shake loose a recalcitrant solution. As crystallographers aim
      to solve larger macromolecular complexes that more faithfully depict the actors
      in cellular events, having existing phase information for parts of those
      biological machines will reinforce the technological advancements in data
      collection and structure solution that have already produced mammoth structures
      like the ribosome, yielding an ever-clearer picture of the inner workings of
      biology.

PMID- 17172764
TI  - Phase determination using halide ions.
AB  - A short soak of protein crystals in cryosolution containing bromides or iodides
      leads to incorporation of these ions into the ordered solvent shell around the
      protein surface. The halide ions display significant anomalous signal, bromides
      in the vicinity of the absorption edge at 0.92 A, and iodides at longer
      wavelengths, e.g., provided by the copper sources. Bromides can, therefore, be
      used through multiwavelength anomalous diffraction or single-wavelength anomalous
      diffraction (SAD) techniques and iodides through SAD or multiple isomorphous
      replacement (MIRAS) phasing. The halide cryosoaking approach involves very little
      preparative effort and offers a rapid and simple way of solving novel protein
      crystal structures.

PMID- 17172765
TI  - The same but different: isomorphous methods for phasing and high-throughput
      ligand screening.
AB  - Isomorphous difference methods allow rapid and detailed visualization of
      localized changes in macromolecular structures, whether as a result of mutation
      or the binding of ligands. Practical aspects of isomorphous methods and
      differential crystallography are presented, particularly in their application to
      the phasing of new structures by multiple isomorphous replacement and the
      detection and characterization of ligand binding. Techniques for maintaining
      isomorphism between crystals to maximize the differential signal are covered, as
      are the computational steps involved in generating difference electron density
      maps. Frontier applications such as determining single-site ligand-binding
      affinities crystallographically, high-throughput screening of combinatorial
      compound libraries, in crystallo competition assays, and inferring protein
      function via exogenous ligand-binding screens are discussed.

PMID- 17172766
TI  - Substructure determination in multiwavelength anomalous diffraction, single
      anomalous diffraction, and single isomorphous replacement with anomalous
      scattering data using Shake-and-Bake.
AB  - A general method for selenium and sulfur substructure determination using the
      Shake-and-Bake (SnB) algorithm as implemented in SnB in conjunction with
      anomalous difference E magnitudes is presented. The protocol can be used for Se
      Met multiwavelength anomalous diffraction, seleneomethionine single anomalous
      diffraction (SAD), S-SAD and S/Se-single isomorphous replacement with anomalous
      scattering data and with minor modifications for other heavy atom derivatives,
      such as the location of halides.

PMID- 17172767
TI  - Substructure determination in isomorphous replacement and anomalous diffraction
      experiments.
AB  - The determination of the substructure of heavy atoms or anomalous scatterers is a
      central step in experimental-phasing procedures. We give an overview of commonly
      used methods for substructure determination, including estimation of substructure
      structure factors, Patterson methods, direct methods, dual-space recycling
      procedures, and methods for substructure refinement and completion. This chapter
      also includes an annotated list of available program packages.

PMID- 17172768
TI  - Automated structure solution with autoSHARP.
AB  - We present here the automated structure solution pipeline "autoSHARP." It is
      built around the heavy-atom refinement and phasing program SHARP, the density
      modification program SOLOMON, and the ARP/wARP package for automated model
      building and refinement (using REFMAC). It allows fully automated structure
      solution, from merged reflection data to an initial model, without any user
      intervention. We describe and discuss the preparation of the user input, the data
      flow through the pipeline, and the various results obtained throughout the
      procedure.

PMID- 17172769
TI  - Introduction to macromolecular refinement.
AB  - The process of refinement is such a large problem in function minimization that
      even the computers of today cannot perform the calculations to properly fit X-ray
      diffraction data. Each of the refinement packages currently under development
      reduces the difficulty of this problem by utilizing a unique combination of
      targets, assumptions, and optimization methods. This chapter summarizes the basic
      methods and underlying assumptions in the commonly used refinement packages. This
      information can guide the selection of a refinement package that is best suited
      for a particular refinement project.

PMID- 17172770
TI  - Quality control and validation.
AB  - This chapter discusses two important aspects of the structure determination
      process that are related to the accuracy and reliability of the crystallographic
      model under investigation. Quality control is defined as the analysis of an
      intermediate model to identify aspects of it that are unusual in some sense and
      that could, therefore, be a result of errors in the model building or refinement
      process. Any such errors need to be fixed, if at all possible, prior to analysis
      and publication of the model. Validation is the process of assessing the
      reliability of the final model (or certain aspects of it, e.g., the active site
      residues) that is about to be analyzed, published, deposited, and possibly used
      in follow-up studies.

PMID- 17172771
TI  - Crystallographic software: a sustainable resource for the community.
AB  - Virtually all software is constantly changing and evolving (and crystallographic
      software is no exception), which makes it nearly impossible to write a chapter
      that will remain current. In this chapter, we introduce CRYSTAL, a website
      (http://crystal.uvm.edu) where a comprehensive list of available crystallographic
      packages for each step of macromolecular structure determination will be
      maintained. Additionally, we provide links to books, journals, and a number of
      educational sites on crystallography. For each program/site included at CRYSTAL,
      a detailed description will include: the most current version, the authors, and
      appropriate operating systems to host the program. Links to download the
      programs, available tutorials, and references to cite when using the program/site
      are also provided.

PMID- 17172772
TI  - Attention problems among children with a positive family history of alcohol abuse
      or dependence and controls. Prevalence and course for the period from preteen to
      early teen years.
AB  - This longitudinal study investigated the scope and course of attention problems
      over a period of time from preteen (ages 7-12 years) to early teen years (ages 13
      17 years). We compared symptoms in subjects with and without a family history
      (FH) of alcohol abuse or dependence from among families without evidence of
      antisocial personality disorder. Evaluations of attention problems for the
      offspring were based on the Child Behavior Checklist and a validated
      semistructured interview carried out with the mother. The findings indicate no
      higher risk for attention problems and attention-deficit hyperactivity disorder
      (ADHD)-like symptoms in the children of families with an alcohol use disorder.
      Regarding the course of problems, the ADHD symptom count tended to decrease over
      time, especially for children without a FH of alcohol abuse or dependence.
      Further research will be needed to determine whether results can be replicated
      with families from different social strata and including subjects with the
      antisocial personality disorder.

PMID- 17172773
TI  - Pilot cluster-randomised trial of adjunctive motivational interviewing to reduce
      crack cocaine use in clients on methadone maintenance.
AB  - This pilot trial explored the effectiveness of an adjunctive single session of
      motivational interviewing (MI) to reduce crack cocaine use in a methadone
      maintenance treatment population. Twenty-nine participants were cluster
      randomised by clinician to MI or a crack information control condition as part of
      treatment as usual. The intervention had a modest impact on one crack cocaine
      measure but was not statistically significant in this small sample. A large and
      statistically significant reduction in heroin use amongst those in the MI
      condition was observed. This pilot study demonstrated that it was feasible to
      incorporate a psychosocial intervention within a busy outpatient methadone
      maintenance programme and the findings support the value of undertaking a larger
      trial.

PMID- 17172774
TI  - Crack cocaine: a five-year follow-up study of treated patients.
AB  - OBJECTIVES: To follow-up a group of 131 crack cocaine users and examine drug use,
      treatment experience, employment status, involvement in crime and mortality at 2
      and 5 years. METHODS: Consecutive crack-dependent patients who were admitted to a
      detoxification unit in Sao Paulo between 1992 and 1994 were re-interviewed on two
      occasions: 1995-1996 and 1998-1999. RESULTS: 5 years after treatment information
      was obtained on 124 (95%) of the original cohort. 39.7% (n = 52) of the patients
      reported having been abstinent from cocaine for at least the last year, and 21.4%
      (n = 28) had used the drug. Of those subjects not using cocaine at 2 years, 19
      (62%) were still abstinent at 5 years. Twenty-three (17.6%) patients had died by
      the 5-year follow-up with homicide, due to firearms or other weapons, being the
      commonest cause (n = 13). The annual adjusted mortality rate for the sample was
      24.92 deaths/1,000 individuals, the excess mortality rate was of 21.64
      deaths/1,000 individuals, and the standardized mortality ratio was 7.60. A
      history of injecting drug use, unemployment at the time of the index admission
      and administrative discharge at the index admission were factors that contributed
      to the risk of dying over the next 5 years. CONCLUSIONS: There was a progressive
      movement towards abstinence over the follow-up period, and there was evidence
      that once abstinence had been achieved it was maintained. On the other hand, the
      mortality rate was extremely high and was higher among those who were still using
      crack at 2 years.

PMID- 17172775
TI  - Naltrexone-assisted rapid methadone discontinuation: a pilot study.
AB  - Slow downtitration as a methadone discontinuation method is time-consuming and
      associated to high dropout rates. Whereas ultra-rapid opiate detoxification
      methods have recently gained some popularity, they are expensive and may be
      associated with particular problems in methadone patients. In the present study,
      a 3-day detoxification procedure accelerated with a unique dose of naltrexone was
      used in 10 methadone-substituted patients. Whereas the treatment resulted in a
      shortened withdrawal syndrome, which was satisfactorily controlled by the drugs
      used, a two-phase course was observed, some symptoms reappearing between the end
      of day 2 and the beginning of day 3. The first phase of withdrawal symptoms was
      attributed to the antagonistic effect of naltrexone, which possibly also improved
      under the weakening of naltrexone. The second phase of withdrawal symptoms may be
      related to falling methadone plasma levels.

PMID- 17172776
TI  - Alcohol screening in general practices using the AUDIT: how many response
      categories are necessary?
AB  - AIMS: The Alcohol Use Disorders Identification Test (AUDIT) is a common screening
      instrument. This study analyses if response categories of the AUDIT might be
      dichotomized without affecting the psychometric properties of the questionnaire.
      METHODS: Participants between 18 and 65 years were recruited from general
      practices in two northern German cities. In total, 10,803 screenings were
      conducted (refusal rate: 5.9%). For those who were screened positive, the Munich
      Composite International Diagnostic Interview (M-CIDI) was used for identification
      of 12-month Alcohol Use Disorders and at-risk consumption (exceeding 20/30 g per
      day). Abstinent subjects and screening positives without diagnostic interview
      were excluded from the analysis, leaving a sample of 7,112 subjects. ROC-Curves
      were calculated separately for each item in order to identify an optimal cut-off
      value. Finally, a version of the AUDIT based on dichotomized items was compared
      to the original version and its short-form, the AUDIT version based on three
      questions dealing with consumption AUDIT-C. RESULTS: As an optimal cut-off value
      for items on consumption, drinking at least once a week, having more than 1-2
      drinks per occasion, and drinking 6 or more drinks in one sitting at least once a
      month were identified. For all questions on alcohol-related problems or
      dependence symptoms, having 'ever occurred' differed best between subjects with
      and without Alcohol Use Disorders or at-risk consumption. Sensitivity and
      specificity of the dichotomized version of the AUDIT did not differ from the
      original version, and both full versions performed superior compared to the AUDIT
      C. CONCLUSION: Data indicate that the AUDIT response categories may be
      dichotomized without affecting its validity.

PMID- 17172777
TI  - The relationship of stress, coping, effect expectancies and craving.
AB  - Based on theoretical models of craving and addiction, this study investigated the
      association between stress-related variables and negatively and positively
      reinforcing dimensions of craving (relief and reward craving) in 150 opiate
      addicts, 150 alcohol addicts and 150 non-addicted controls. Stress-distress was
      the most powerful predictor of both dimensions of craving, followed by a lack of
      positive coping strategies whereas expectancies of substance effects seemed to be
      less important. Positive coping strategies were related to reduced craving only
      when they were accompanied by low stress-distress. In non-addicted subjects, only
      positive coping strategies were negatively related to craving. This study
      confirms the important role of stress-distress for the occurrence of craving in
      addicts.

PMID- 17172778
TI  - Origin of the comorbidity of anxiety disorders and alcohol dependence: findings
      of a general population study.
AB  - A representative general population sample (n = 7,076) was used to study
      retrospectively and prospectively the nature of the relationship between co
      morbid alcohol dependence and anxiety disorders. Four different models were
      tested: (1) anxiety disorders increase the risk of alcohol dependence; (2)
      alcohol dependence increases the risk of anxiety disorders; (3) family history or
      childhood traumatisation increase the risk of both alcohol dependence and anxiety
      disorders, and (4) comorbid conditions are a separate psychopathological entity.
      The data show that alcohol dependence does not precede the onset of anxiety
      disorders, that anxiety disorders do precede the onset of alcohol dependence,
      that family history is not very likely to be the third factor explaining the
      elevated comorbidity, and that in women childhood trauma might be partially
      responsible for the association between both disorders. The data are inconsistent
      with regard to comorbidity as a distinct psychopathological entity. These
      findings are of great importance for treatment planning in patients with alcohol
      dependence and comorbid anxiety disorders.

PMID- 17172779
TI  - The role of pharmacies in the care of drug users: what has changed in ten years.
      The case of a Swiss region.
AB  - This article assesses changes over 10 years in the role of pharmacies in the care
      of drug misusers--needle/syringe provision and methadone treatment supervision-
      in the Swiss French-speaking Canton of Vaud (636,000 inhabitants, 238
      pharmacies). A review of data collected in four surveys (1991, 1994, 1996, 2003)
      on the provision of sterile material (and methadone treatment supervision in
      2003) including all the pharmacists of the Canton of Vaud was conducted, as well
      as a review of data of the monitoring of needle exchange programmes introduced
      since 1996 in this canton, and of methadone treatment statistics. In 2003,
      interviews with pharmacists complemented the survey. Pharmacies play an important
      role in the 'frontline' services to drug misusers: the provision of
      needles/syringes to drug users by pharmacies remains important in spite of a
      decrease in the provision of sterile material by them since the advent of needle
      exchange programmes, and they are included in the supervision of two thirds of
      the methadone treatments. However, they do not feel integrated enough in the
      network of care to drug misusers and ask for more training and better recognition
      of their role.

PMID- 17172780
TI  - 5-Year trends in use of hallucinogens and other adjunct drugs among UK dance drug
      users.
AB  - AIMS: To describe and assess trends in the use of hallucinogens and other adjunct
      drugs over a 5-year period. DESIGN: Repeated-measures cross-sectional survey.
      SETTING AND PARTICIPANTS: Annual magazine-based survey targeting people who use
      drugs in dance contexts. MEASUREMENTS: Lifetime use prevalence (ever used); age
      of first use; current use prevalence (any use within the last month), and extent
      of use within the last month (number of days used) for LSD, psilocybin, ketamine,
      GHB and nitrates. FINDINGS: Prevalence increases for psilocybin, ketamine, GHB
      and nitrates use have been detected, with a sharp recent rise in current
      psilocybin use in 2002-2003 contrasting with more gradual and comprehensive
      evidence of increased ketamine use throughout the period 1999-2003. The declining
      prevalence of LSD use in general population surveys is replicated in this
      sentinel population study. CONCLUSIONS: The rise in prevalence of hallucinogen
      and other adjunct drugs identified among dance drug users may be mirrored by
      wider prevalence increases among young people with a consequent need to study
      these trends carefully and to develop effective interventions, where required.

PMID- 17172781
TI  - Sex differences in frequency and intensity in reading and voice range profiles
      for Taiwanese adult speakers.
AB  - The purposes of the study were to (1) compare speaking frequency and speaking
      intensity between normal adult Taiwanese females and males, and (2) compare the
      physiological frequency and physiological intensity between normal adult
      Taiwanese females and males. Forty normal young Taiwanese females and 40 males
      were selected for study. The frequency and intensity variables in reading and in
      vocal range profiles were collected and analyzed. The independent t test was used
      to find a statistical significance between the female and male groups. In
      reading, the speaking fundamental frequency, the highest and lowest speaking
      ranges, and the maximum range of speaking fundamental frequency for the female
      group were significantly greater than those for the male group. In vocal range
      profiles, the lowest and highest frequencies, and the soft and loud voice for the
      female group were significantly greater than those for the male group. The
      maximum dynamic frequency range for the male group was significantly greater than
      that for the female group. The frequency and intensity ranges for both sexes in
      this study were greater than other findings for nontonal language speakers. The
      data may provide a voice assessment tool for Mandarin speakers in Taiwan and in
      other countries.

PMID- 17172782
TI  - Incidence of word finding deficits in normal aging.
AB  - The incidence and pattern of word finding deficits was investigated in a group of
      50 non-neurologically-impaired older adults, ranging in age from 54 to 75. The
      Test of Adolescent/Adult Word Finding (TAWF; German, 1990) was administered to
      all individuals. Overall, 28% of the adults exhibited abnormal word finding
      standard scores on the TAWF. Specifically, 3 word finding profiles were observed:
      (1) normal psychometric scores and normal word retrieval performance across all
      subtests; (2) normal psychometric performance with selective impairment on
      picture naming of nouns, and (3) abnormal word finding standard scores with
      impaired performance on more than 1 subtest, which included picture naming of
      nouns as well as category naming. The most frequently occurring error type on
      picture naming of nouns was productions that were semantically related to the
      target. The results are discussed relative to the representation of information
      in semantic memory and its interaction with the lexicon.

PMID- 17172783
TI  - Objective voice analysis in dysphonic patients: new data including nonlinear
      measurements.
AB  - OBJECTIVES/HYPOTHESIS: This report describes a comparative study of objective
      voice evaluation using a multiparametric protocol including aerodynamic
      parameters and linear and nonlinear acoustic parameters recorded on an EVA(R)
      workstation and perceptual voice analysis by a jury. STUDY DESIGN: A total of 449
      samples were retrospectively selected including 391 patients with pathological
      voices (308 women and 141 men) and 58 controls with normal voices (38 women and
      20 men). A prospective complementary study concerning 43 female patients and 3
      controls is presented. METHODS: Objective measures included fundamental frequency
      (Fo), intensity, jitter, signal-to-noise ratio (SNR), Lyapunov coefficient (Lya),
      oral airflow (OAF), estimated subglottic pressure (ESGP), maximum phonatory time
      (MPT) and vocal range. A jury of 4 experienced listeners was instructed to
      classify voice samples (continuous speech) according to the G (overall dysphonia)
      component of the GRBAS score on a Visual Analogue Scale (VAS) secondarily
      transformed in a scale ranging from 0 for normal to 3 for severe dysphonia.
      RESULTS: It was shown that a nonlinear combination of only 7 parameters in women
      (vocal range, Lya, ESGP, MPT, OAF, SNR, and Fo) and 6 parameters in men (vocal
      range, Lya, OAF, ESGP, Fo, SNR) allowed classification of 81% voice samples in
      the same grade as the jury in women and 84% in men. In the prospective study,
      80.5% were correctly classified with the same set of objective measurements.
      DISCUSSION: The relative importance of the different objective parameters in this
      type of discriminant analysis is dealt with. Special emphasis is placed on Lya.

PMID- 17172784
TI  - The nasality severity index: an objective measure of hypernasality based on a
      multiparameter approach. A pilot study.
AB  - There is a need for an objective measure that describes normal resonance and
      resonance disorders. The current standard of practice has not led to
      mismanagement but a refined objective assessment protocol will benefit a more
      precise objective assessment of velopharyngeal disorders. The purpose of the
      present study is to construct a nasality severity index (NSI) that reflects the
      multidimensional nature of resonance. Objective and subjective assessment
      techniques were used to determine the nasalance, the nasality and aerodynamic
      capacities in 21 children with cleft palate and a control group of 25 children
      without cleft palate. Stepwise logistic regression was used to determine the
      optimal index. The NSI consists of a linear combination of 4 variables, where
      each variable has a different weight. The equation is: NSI = -60.69 - (3.24 x
      percent oral text) - (13.39 x Glatzel value /a/) + [0.244 x maximum duration time
      (seconds)] - (0.558 x % /a/) + (3.38 x percent oronasal text). NSI sensitivity is
      88% and specificity is 95%. Daily clinical use of the NSI has shown it to be an
      efficient and practical tool to describe the presence of hypernasality. Three
      distinct follow-up cases are presented to illustrate the impact of a surgical
      technique, the use of a speech bulb and velopharyngeal biofeedback training on
      NSI. The implementation of the NSI may help clinicians to quantitatively assess
      the severity of nasality disorders beside the perceptual judgments.

PMID- 17172786
TI  - [Human Y chromosome: structure and biological role].
AB  - Y chromosome differs from other human chromosomes. It is found in cells of the
      male persons only. Different human phenotypes are associated with non-recombinant
      region of Y chromosome. This chromosome is of great significance in the human sex
      determination and the development of male gametes (spermatogenesis). Testes
      develop in embryos which have the Y chromosome, and ovaries develop in embryos
      which have no Y chromosome. SRY (sex-determining region of the Y chromosome) gene
      determines the male phenotype. Translocation of this gene determines sex
      reversal. The aim of this article was to review the structure and biological
      functions of the human Y chromosome.

PMID- 17172785
TI  - Swallowing difficulties reported by adults infected with HIV/AIDS attending a
      hospital outpatient clinic in Gauteng, South Africa.
AB  - OBJECTIVE: Swallowing difficulties can exert a profound effect on quality of
      life, may result in reduced nutritional intake and place individuals at risk of
      aspiration. However, there is little data available on the swallowing
      difficulties occurring within the HIV/AIDS population in South Africa. A
      descriptive study was therefore conducted to document the presence of reported
      swallowing difficulties in a sample of adults with HIV. PATIENTS AND METHODS: One
      to-one semi-structured interview schedules were administered to 120 adults with
      HIV attending a clinic in Gauteng, and medical records were evaluated to document
      the presence of reported swallowing difficulties. RESULTS: Participants described
      a range of swallowing difficulties and the number of swallowing difficulties
      reported by participants was negatively correlated with CD4 count. Swallowing
      difficulties were significantly associated with various opportunistic diseases
      and related medical pathologies. Prescribed medications were associated with
      reported swallowing difficulties. Treatment of swallowing difficulties was mainly
      medical in nature. Swallowing difficulties had affected quality of life.
      CONCLUSIONS: From the results it was concluded that speech therapists have a role
      to play in the assessment and treatment of swallowing difficulties in individuals
      with HIV/AIDS.

PMID- 17172787
TI  - [Complications after spinal cord injuries and their influence on the
      effectiveness of rehabilitation].
AB  - In this article, literature data on complications after spinal cord injuries and
      their influence on the efficiency of rehabilitation are analyzed. The spinal cord
      injury is associated with physical and psychological disorder that causes
      disability and requires intensive treatment. Authors in their articles indicate
      that many people after spinal cord injuries have complications. The most common
      complications are: skin breakdown, urinary tract infection, pulmonary
      complications, spasticity, pain, autonomic dysreflexia, cardiovascular disease,
      osteoporosis and fractures, heterotopic ossification, deep vein thrombosis. These
      complications make patients' rehabilitation more difficult and limit their self
      care independence, and the treatment of such complications is very expensive.

PMID- 17172788
TI  - Eyelid malposition: lower lid entropion and ectropion.
AB  - Correcting entropion and ectropion successfully requires knowledge of the eyelid
      problems, because understanding of these abnormalities is a key to planning a
      successful surgical procedure. Entropion is a condition in which the eyelid
      margin turns inwards against the globe. It is divided into following categories:
      congenital and acquired, which may be involutional or cicatricial. Ectropion is a
      malposition in which the lid falls away or is pulled away from its normal
      apposition to the globe. The condition is classified as congenital and acquired,
      which is divided into following categories: involutional, cicatricial, paralytic,
      and mechanical. Therefore, there are some common anatomic changes for both
      entropion and ectropion as well as specific changes that are unique to each
      eyelid malposition. Typically, instability of the eyelid is caused by either
      horizontal laxity or disinsertion or attenuation of the lower eyelid retractors
      to the inferior tarsal border, so surgical procedures should be directed at
      correcting the horizontal and vertical instability of the lid. Classification,
      etiology, underlying anatomic changes in the lid, principles of surgical
      treatment of entropion and ectropion are reviewed in this article.

PMID- 17172790
TI  - [Dietary characteristics of patients with inflammatory bowel diseases].
AB  - OBJECTIVE: To evaluate nutritional status and dietary habits of Lithuanian
      patients with ulcerative colitis and Crohn's disease and to compare with those of
      healthy controls. MATERIALS AND METHODS: A case-control study was conducted in
      the Department of Gastroenterology, Kaunas University of Medicine Hospital. A
      total of 101 patients with ulcerative colitis, 44 with Crohn's disease, and 178
      healthy controls were examined with the help of standard self-report
      questionnaire about daily dietary habits. Healthy controls were evaluated in
      primary care centers during preventive examinations. Body mass index was
      calculated for all patients in a standard way. RESULTS: There was no
      statistically significant difference between patients and controls concerning
      consumption of coffee, tea, chewing gum, type of fat for meal preparation, white
      bread, cooked potatoes and sausages, non-carbonated water. Patients with
      inflammatory bowel diseases statistically significantly less frequently consumed
      fresh milk, cheese, fish, fried potatoes, and soda drinks. Patients with Crohn's
      disease statistically significantly less frequently consumed fresh fruits and
      patients with ulcerative colitis--fresh vegetables as compared to controls. Body
      mass index of patients with inflammatory bowel diseases was significantly lower
      compared to controls, and patients with Crohn's disease had significantly lower
      body mass index than ulcerative colitis patients. CONCLUSIONS: Patients with
      inflammatory bowel diseases have lower body mass index than healthy controls.
      Patients consume fresh milk, cheese, canned and fresh vegetables and fruits less
      frequently; therefore, primary care physicians and patients should be provided
      with teaching and more information about nutrition issues.

PMID- 17172789
TI  - Prevalence and risk factors of genital Chlamydia trachomatis infection.
AB  - The aim of the study was to provide a survey and generalization of literature
      data on the epidemiological situation of Chlamydia trachomatis infection in
      various countries, preventive screenings and risk factors of the infection. We
      performed a survey of articles published during 1998-2005 and selected from
      bibliographical medical search databases presenting data on the prevalence of
      Chlamydia trachomatis and the main risk factors for this sexually transmitted
      infection. Chlamydial infection is the most common among sexually transmitted
      genital infections worldwide. It has been found that the main risk factors for
      Chlamydia trachomatis infection are age, irregular and/or accidental sexual
      relationships and change of sexual partners, failure to use or erratic use of
      barrier contraception during intercourse, and insufficient knowledge about sexual
      life and care for one's sexual health. Most countries do not have national
      preventive screening programs or exhaustive information about the prevalence of
      Chlamydia trachomatis infection. The comparison of the prevalence and incidence
      of Chlamydia trachomatis infection among different countries is complicated due
      to the different diagnostic methods and sample selection techniques applied;
      however, in order to decrease the prevalence of chlamydial infection and its
      impact on the reproductive health of the society, significant attention should be
      paid to sexual education, preventive screening of people in high-risk groups, as
      well as to early diagnostics and timely treatment.

PMID- 17172791
TI  - Investigations of ocular changes, extraocular muscle thickness, and eye movements
      in Graves' ophthalmopathy.
AB  - The aim of this study was to evaluate ocular changes, to measure the thickness of
      extraocular muscles, and to assess eye movements in patients with active Graves'
      ophthalmopathy. MATERIAL AND METHODS: We examined 27 patients (18 women and 9
      men) with Graves' ophthalmopathy. Their age ranged from 17 to 59 years; mean age
      was 42.7+/-2.9 years. The control group consisted of 30 healthy persons aged
      43.6+/-2.6 years. All patients underwent a complete ophthalmic examination
      including best-corrected Snellen visual acuity testing, measurements of proptosis
      using Hertel exophthalmometer, echography using A/B mode Mentor Advent ultrasonic
      diagnostic imaging system, ocular motility, slit-lamp and ophthalmoscopic
      examination. RESULTS: The examination showed a significant increase of proptosis,
      periorbital edema in 66.67%, chemosis in 59.26%, injection of conjunctiva in
      45.15% of patients. The majority of patients with infiltrative form of Graves'
      ophthalmopathy had a significant enlargement of medial rectus muscle (from 5.0 to
      5.9 mm in 46.3%, from 6.0 to 6.9 mm in 22.22% of eyes) and inferior rectus muscle
      thickness (from 5.0 to 5.9 mm in 33.33%, from 6.0 to 6.9 mm in 24.07% of eyes),
      disturbances in upward (less than 30 degrees in 62.96%) and lateral eye movements
      (from 30 to 50 degrees in 77.78%). CONCLUSIONS: The results of ocular examination
      showed an increase of proptosis, periorbital edema, chemosis and injection of
      conjunctiva in patients with Graves' ophthalmopathy. Ultrasound investigations
      showed a marked increase in the volume of medial and inferior eye muscle. In
      patients with Graves' ophthalmopathy, the changes in ocular motility (upward and
      lateral gaze) were detected.

PMID- 17172792
TI  - Impedance cardiography for aortic balloon counterpulsation impact assessment on
      patients hemodynamics during acute myocardial infarction.
AB  - BACKGROUND AND OBJECTIVE: The evaluation of hemodynamics in patients with acute
      myocardial infarction is crucial. Intra-aortic balloon pumping or
      counterpulsation in patients with cardiogenic shock is supposed to be monitored
      exceptionally by invasive methods for assessment of hemodynamics. However,
      noninvasive methods might have place in monitoring these patients. The objective
      of the study was to evaluate the possibility of applying noninvasive methods for
      evaluation of hemodynamics during acute myocardial infarction complicated by
      cardiogenic shock and managed by intra-aortic balloon pumping. PATIENTS AND
      METHODS: A total of 16 patients were investigated according to the study
      protocol. Anterior acute myocardial infarction was diagnosed in 11 (68.75%)
      patients, inferior--in 4 (25%), circular--in 1 (6.25%). Primary percutaneous
      transluminal coronary angioplasty was successfully performed in 7 (43.75%)
      patients, unsuccessfully--in 1 (6.25%) patient, who died within the first 18
      hours. Half of patients (50%) underwent cardiac surgery within the first two
      weeks. Mortality rate was 68.75% (11 patients). A prospective controlled study
      was carried out to compare two different methods--intermittent thermodilution
      (ITD) and impedance cardiography (ICG)--for simultaneous cardiac output
      measurements in patients with acute myocardial infarction complicated by
      cardiogenic shock and managed by intraaortic balloon counterpulsation.
      Statistical analysis was performed with Bland-Altman and linear regression.
      RESULTS: Correlation coefficient was calculated comparing cardiac output values
      derived from ICG and ITD; it ranged from 0.24 to 0.98 in separate patients. It
      was observed a weak correlation of ICG and ITD measurements before initiation of
      intra-aortic balloon pumping--0.24-0.27 in separate cases. The correlation
      improved during intra-aortic balloon pumping--0.58-0.98 and at the termination of
      intra-aortic balloon pumping--0.67-0.97. The observed correlation was more
      pronounced in patients not receiving high doses of inotropes and ranged 0.58-0.98
      while for patients receiving high doses of inotropes correlation was less
      pronounced 0.29-0.5. CONCLUSIONS: Significant correlation of cardiac output
      values was observed between the impedance cardiography and intermittent
      thermodilution techniques during intra-aortic balloon counterpulsation.
      Noninvasive evaluation of hemodynamic indices by continuous monitoring of
      impedance cardiography during acute myocardial infarction, complicated by
      cardiogenic shock and managed by intra-aortic balloon counterpulsation is a
      reliable method for further application.

PMID- 17172793
TI  - Morphometric analysis of pulpal myelinated nerve fibers in human teeth with
      chronic periodontitis and root sensitivity.
AB  - BACKGROUND: The reasons why root sensitivity occurs in some periodontally
      diseased teeth are still unknown. It is possible that root sensitivity may be
      related to changes of intradental myelinated nerve fibers, which are responsible
      for dentine sensitivity. OBJECTIVE: The aim of this study was to define the
      pattern of myelinated nerve fiber changes in the pulps of teeth with and without
      root sensitivity in the presence of chronic periodontitis. MATERIALS AND METHODS:
      A total of 33 cross-sectioned human dental pulp specimens were collected from
      noncarious, intact, permanent teeth sensitive to electric and thermal (cold)
      stimulus (10 hypersensitive teeth with chronic periodontitis (HTPP group), 15
      nonsensitive teeth with chronic periodontitis (NTPP group), and 8 nonsensitive
      teeth with healthy periodontium (control group)). The morphometric parameters
      were estimated using light microscopy and image-analyzing computer program Image
      Pro Plus. RESULTS: The means of myelinated nerve fiber density, fiber and axon
      diameter, area, perimeter, length, width, g ratio, index of circularity, and
      myelin sheath thickness in NTPP group significantly differed from HTPP group and
      the control group teeth (p<0.001). The great reduction in the density of
      myelinated nerve fibers in NTPP group was accompanied by unequal decrease in the
      number of very large-diameter myelinated nerve fibers. The mean values of
      morphometric parameters of all myelinated nerve fibers in HTPP group were almost
      the same as those in the control teeth, and no significant difference was
      observed. CONCLUSION: The findings of the present study suggest that the reason
      for enhanced root sensitivity has likely nothing to do with changes of the
      innervation of myelinated nerves in the dental pulp. While, decreased sensitivity
      of periodontally diseased teeth may be related to the degeneration of myelinated
      nerve fibers in the pulp.

PMID- 17172794
TI  - [Disseminated ovarian, bone, and bone marrow metastases from gastric cancer].
AB  - The main cause of death in patients with gastric cancer is disease dissemination.
      It is not clear why gastric cancer metastasizes to different organs. Early
      detection and destruction of circulating malignant cells before developing
      metastases may markedly improve survival of these patients. Krukenberg tumors
      (metastases of non-gynecological origin in the ovaries) usually are circular cell
      carcinomas of gastric cancer. Bone metastases of gastric cancer are rare, but if
      they are diagnosed, patients survive only 2-5 months on the average. Disseminated
      bone marrow metastases from gastric cancer do not always show the sudden course
      of the disease, but hematological complications are signs of poor prognosis.
      Hematological paraneoplastic disorders can be miscellaneous: they usually
      manifest as anemia of various origin, as leucocytosis in half of the patients, as
      leukemoid reactions in one-third of the patients, and as hemolysis and
      thrombocytopenia in half of the patients (often with disseminated intravascular
      coagulation). Currently, chemotherapy is the most effective treatment for
      outspread gastric cancer. Unfortunately, there is no exclusively effective scheme
      for treatment. Lymph node metastases are more sensitive to chemotherapy than
      primary gastric cancer, while in contrary, hepatic metastases are less sensitive
      than primary gastric cancer. This article includes a literature review and a rare
      case of gastric cancer.

PMID- 17172795
TI  - The effect of passive foot flexion on blood circulation in sports and clinical
      medicine.
AB  - The aim of the study was to analyze the effect of the passive foot flexion on
      peripheral and systemic blood circulations in the state of rest of persons
      adapted to endurance physical loads, and on patients during surgery. METHODS: In
      the first series of experiments which included 16 males in recumbent supine
      position adapted to endurance physical loads, the effect of the passive foot
      flexion by applying a leg muscle activator on the systemic and peripheral blood
      circulations was analyzed. In the second series of experiments conducted with 6
      males and 12 females, the passive foot flexion was aimed at preventing
      thromboembologenesis during the intraoperative period. RESULTS: After a session
      of the passive foot flexion applied to persons adapted to endurance physical
      loads, the venous reserve volume in them increased to 1.68+/-0.3 mL/100 mL
      (p<0.05). The maximal venous emptying rate increased to 48.3+/-8.8 mL/100 mL/min
      (p<0.05). After 15 min of the passive foot flexion, the indices of the systemic
      blood circulation were analogous to the ones before passive foot flexion. The
      maximal venous emptying rate in the calves of the left and right legs at the end
      of the surgery decreased to 59.7+/-4.7 mL/100 mL/min (p>0.05) and to 62.9+/-4.0
      mL/100 mL/min (p>0.05), respectively. CONCLUSIONS: The passive foot flexion
      applied to persons adapted to endurance physical loads increases venous reserve
      volume and maximal venous emptying rate. During the intraoperative period, the
      passive foot flexion increases maximal venous emptying rate from the triceps
      muscle of the calf thus decreasing the possible danger of thromboembologenesis.

PMID- 17172796
TI  - The search for the criteria in reforming health care: evaluation of the spatial
      accessibility of primary healthcare service.
AB  - This article analyzes the spatial accessibility of primary healthcare services,
      i.e. the population's possibilities to receive healthcare services within an
      acceptable period of time in healthcare institutions situated in a certain
      territorial-administrative unit--the municipality. The aim of the study was to
      develop the technique for the quantitative evaluation of the spatial
      accessibility of primary healthcare services in different territories. The object
      of the study was the network of primary healthcare institutions and their
      subdivisions in the municipalities of Klaipeda, Taurage, and Vilnius districts.
      The methods of the study were geometrical modeling and applied graphics used for
      the quantitative determination of the ratios between the total zone area of the
      accessible primary healthcare institutions and the area of the respective
      municipal territory. The result of the study was the developed and proposed
      technique allowing for the evaluation of the spatial accessibility of primary
      healthcare institutions. The proposed technique of the evaluation of the spatial
      accessibility of primary healthcare services may be valuable in solving the
      problems of the development of primary healthcare institutions primarily in the
      rural regions of Lithuania. The quantitative expression of the evaluation could
      be used in decision-making related to investments into the development of the
      primary healthcare institution network in different administrational units of the
      country. The method of geometrical modeling involving the application of digital
      graphics may create preconditions for the creation of the geographical
      information system of the primary healthcare institution network in Lithuania.

PMID- 17172797
TI  - [The relationship of eating behavior to body dissatisfaction and physical and
      psychological abuse in childhood].
AB  - The aim of this study was to determine the relationship of disordered eating
      behavior to body dissatisfaction and physical and psychological abuse in
      childhood. MATERIAL AND METHODS: A total of 299 first- through fourth-year female
      students of Kaunas University of Medicine and Vytautas Magnus University took
      part in the survey. The respondents filled in the Eating Attitude Test-26 (EAT
      26), Body Shape Questionnaire (BSQ) and answered the questions about parental
      physical and psychological abuse in childhood. RESULTS: Women who are
      dissatisfied with their body image diet more often (p<0.05), and they are
      significantly more likely to display bulimic behavior (p<0.05). Women who have
      experienced parental physical and psychological abuse demonstrate more anorexic
      behavior (p<0.05). In addition, they diet more often (p<0.05). CONCLUSIONS: Women
      who are dissatisfied with their body image show more disordered eating behavior:
      they diet more often and are more likely to display bulimic behavior. Parental
      physical and psychological abuse in childhood is related to eating behavior
      characteristic of anorexia nervosa. Parental physical and psychological abuse in
      childhood is not related to bulimic behavior. Women who have experienced parental
      physical and psychological abuse in childhood do not differ in body
      dissatisfaction from women who have not experienced such an abuse in their
      childhood.

PMID- 17172798
TI  - [The main aspects of symptomatic therapy of chronic heart failure].
AB  - The main aims of the treatment of chronic heart failure are to improve and to
      maintain the quality of life, to increase duration of life, to decrease
      mortality, to prevent diseases leading to the heart failure development, and to
      prevent the progression of heart failure. Diuretics are the drugs of first choice
      for the treatment of congestive heart failure. They can improve the quality of
      patient's life quite quickly. Noncompliance to methodological diuretic use can
      cause a serious damage such as metabolic disorders, arrhythmias, and even sudden
      death. Loop diuretics are the drugs of choice. Resistance to diuretics occurs in
      10-20% of the cases during the course of treatment; therefore, drug combination
      as well as dose modification is required. Diuretics are not recommended to use
      alone for a symptomatic relief. They are prescribed in combination with beta
      blockers, angiotensin-converting-enzyme inhibitors, and/or angiotensin receptor
      blockers for a continuous pathogenetic therapy of congestive heart failure.
      Digoxin in combination with diuretics is the drug of choice for treatment of
      heart failure when tachyarrhythmia or severe systolic left ventricular
      dysfunction appears or it is impossible to administer beta-blockers. In this
      article, the guidelines of European Society of Cardiology and also American
      College of Cardiology and American Heart Association for the symptomatic
      management of congestive heart failure, updated in 2005, are reviewed.

PMID- 17172799
TI  - Autophagy genes protect against disease caused by polyglutamine expansion
      proteins in Caenorhabditis elegans.
AB  - Expanded polyglutamine (polyQ) proteins aggregate intracellularly in Huntington's
      disease and other neurodegenerative disorders. The lysosomal degradation pathway,
      autophagy, is known to promote clearance of polyQ protein aggregates in cultured
      cells. Moreover, basal autophagy in neuronal cells in mice prevents
      neurodegeneration by suppressing the accumulation of abnormal intracellular
      proteins. However, it is not yet known whether autophagy genes play a role in
      vivo in protecting against disease caused by mutant aggregate-prone, expanded
      polyQ proteins. To examine this question, we used two models of polyQ-induced
      toxicity in C. elegans, including the expression of polyQ40 aggregates in muscle
      and the expression of a human huntingtin disease fragment containing a polyQ
      tract of 150 residues (Htn-Q150) in ASH sensory neurons. Here, we show that
      genetic inactivation of autophagy genes accelerates the accumulation of polyQ40
      aggregates in C. elegans muscle cells and exacerbates polyQ40-induced muscle
      dysfunction. Autophagy gene inactivation also increases the accumulation of Htn
      Q150 aggregates in C. elegans ASH sensory neurons and results in enhanced
      neurodegeneration. These data provide in vivo genetic evidence that autophagy
      genes suppress the accumulation of polyQ aggregates and protect cells from
      disease caused by polyQ toxicity.

PMID- 17172800
TI  - Autophagy of vascular smooth muscle cells in atherosclerotic lesions.
AB  - Autophagy genes were first identified in the yeast system and some of their
      mammalian orthologues have also been characterized. Increasing lines of evidence
      indicate that various intracellular proteins, including G proteins, mammalian
      target of rapamycin (mTor) and Pl3K/Akt/PKB, of transmembrane signaling pathways
      are involved in the regulation of autophagy genes. We have recently discovered
      autophagy as a mechanism of cell death in atherosclerotic vascular smooth muscle
      cells (VSMCs). Tumor necrosis factor-alpha (TNF-alpha), insulin-like growth
      factor-1 (IGF-1), and 7-ketocholesterol can regulate the expression of autophagic
      genes, including microtubule-associated protein 1 light chain-3 (MAP1LC3) and
      Beclin 1, through Akt/PKB and c-jun N-terminal signal pathways in VSMCs. However,
      the balance between cell death and survival of VSMCs in the fibrous cap of
      atherosclerotic plaques appears to best correlate with plaque instability.
      Understanding the underlying cellular and molecular mechanisms of autophagy can
      provide key insights into the cell death machinery of atherosclerotic diseases.

PMID- 17172802
TI  - Xeno-cannibalism: a survival "escamotage".
AB  - Several lines of evidence have demonstrated that self-cannibalism
      (macroautophagy) is a well regulated process of cell repair as well as of
      molecule and organelle recycling that allows the cells to survive. However,
      autophagic activity also represents a cell death pathway characterized by
      specific features that differentiate autophagy from other cell death processes.
      We found that cells that are able to exert intense autophagic activity were also
      able to engulf and digest entire cell siblings. This phenomenon represents a sort
      of xeno-cannibalism. We wonder whether these two phenomena, self and xeno
      cannibalism, could be related the latter being an exacerbation of the first and
      providing a further survival option to the cells.

PMID- 17172803
TI  - A two-carbon switch to sterol-induced autophagic death.
AB  - Although both cholesterol and plant sterols are abundant in our diets, our
      intestinal epithelial cells selectively and efficiently rid the body of plant
      sterols. However, a rare mutation in plant sterol excretion in humans results in
      the accumulation of plant sterols, particularly sitosterol, in the plasma and
      tissues. Sitosterol differs from cholesterol only in an extra ethyl group on the
      sterol side chain. Significantly, sitosterolemia is associated with accelerated
      atherothrombotic vascular disease, notably myocardial infarction. An important
      process that promotes atherothrombosis is advanced lesional macrophage death,
      leading to plaque necrosis. One of the causes of atherosclerotic macrophage death
      is sterol-induced cytotoxicity. We therefore compared the effects of excess
      intracellular sitosterol vs. cholesterol on macrophage death. Whereas excess
      cholesterol kills macrophages by caspase-dependent apoptosis, sitosterol kills
      macrophages by a caspase-independent pathway involving necroptosis and autophagy.
      The finding that an ethyl group on the sterol side chain fundamentally alters the
      way cells respond to excess sterols adds new insight into the mechanisms of
      sterol-induced cell death and may provide at least one explanation for the excess
      atherosclerotic heart disease in patients with sitosterolemia.

PMID- 17172805
TI  - Autophagic cell death and its importance for fungal developmental biology and
      pathogenesis.
AB  - In order to cause disease in plants, many fungal pathogens develop a specialized
      structure called an appressorium. We have recently shown that the rice blast
      fungus Magnaporthe grisea undergoes a regulated form of programmed cell death
      during appressorium development involving autophagy. Significantly, this form of
      cell death is a prerequisite for plant infection and fungal pathogenesis and part
      of a growing body of evidence implicating autophagy as a key process in fungal
      developmental biology.

PMID- 17172806
TI  - SNP'ing at nasopharyngeal cancer susceptibility: for whom the bell TOLLs.

PMID- 17172804
TI  - A peroxisomal lon protease and peroxisome degradation by autophagy play key roles
      in vitality of Hansenula polymorpha cells.
AB  - In eukaryote cells various mechanisms exist that are responsible for the removal
      of non-functional proteins. Here we show that in the yeast Hansenula polymorpha
      (H. polymorpha) a peroxisomal Lon protease, Pln, plays a role in degradation of
      unfolded and non-assembled peroxisomal matrix proteins. In addition, we
      demonstrate that whole peroxisomes are constitutively degraded by autophagy
      during normal vegetative growth of WT cells. Deletion of both H. polymorpha PLN
      and ATG1, required for autophagy, resulted in a significant increase in
      peroxisome numbers, paralleled by a decrease in cell viability relative to WT
      cells. Also, in these cells and in cells of PLN and ATG1 single deletion strains,
      the intracellular levels of reactive oxygen species had increased relative to WT
      controls. The enhanced generation of reactive oxygen species may be related to an
      uneven distribution of peroxisomal catalase activities in the mutant cells, as
      demonstrated by cytochemistry. We speculate that in the absence of HpPln or
      autophagy unfolded and non-assembled peroxisomal matrix proteins accumulate,
      which can form aggregates and lead to an imbalance in hydrogen peroxide
      production and degradation in some of the organelles.

PMID- 17172807
TI  - The combination of oral and small intestinal mucositis, pediatrics and
      biomarkers: a particularly tricky problem!

PMID- 17172808
TI  - Squeezing data from pancreatic juice.

PMID- 17172809
TI  - Antisense targeting of Mcl-1 has therapeutic potential in gastric cancer.

PMID- 17172810
TI  - Combination therapy with gemcitabine and 5-Fluorouracil: unblocking the pathways
      to survivin?

PMID- 17172811
TI  - The chemokine receptor CXCR4: a homing device for hypoxic cancer cells?

PMID- 17172812
TI  - Piecing together the HIF-1 puzzle: the role of the CTGF as a molecular mechanism
      of HIF-1 regulation.
AB  - Understanding the role that molecular compounds have in cancer is of significant
      interest, as the identification of molecular markers will aid in the prevention
      and elimination of cancer. Completing this expansive puzzle proves to be
      challenging because there is great diversity among tumors, specifically within
      the microenvironment. In a recent article by Chang et al. published in The
      Journal of the National Cancer Institute (Vol., 2006) new insight is provided of
      three specific molecular compounds: hypoxia-inducible factor-1alpha (HIF-1alpha),
      the connective tissue growth factor (CTGF) and the vascular endothelial growth
      factor-A (VEGF-A). As shown by Chang et al., these molecular compounds have
      significant implications in the role of human lung adenocarcinoma, and are shown
      to be integral within this microenvironment. This journal club article reviews
      the study of Chang et al. and briefly discusses the broader implications of their
      findings.

PMID- 17172813
TI  - Exploiting the complex biology of prostate cancer.

PMID- 17172814
TI  - hTERT/re-caspase-3 system induce apoptosis in hTERT-positive cancer cells.
AB  - Apoptosis induction is a promising approach for the treatment of human cancer. To
      achieve this purpose, the design of an expression system capable to induce
      apoptosis specifically in cancer cells is essential. Telomerase is an attractive
      target for delivery of apoptotic genes as an overwhelming majority of cancers
      have telomerase activity whereas most normal cells have low or an absence of
      telomerase activity. Activation of telomerase is tightly regulated at the
      transcriptional level of human telomerase reverse transcriptase (hTERT). In the
      present study, we developed a telomerase-specific delivery system of apoptosis
      inducible gene re-Caspase-3, through utilizing the promoter of the hTERT gene,
      and then investigated its antitumor effect on cancer cells and tissues. The
      reason we used the re-Caspase-3 gene is that it is capable of autocatalytic
      processing and inducing apoptosis independent of the initiator Caspases. Here, we
      demonstrated that the hTERT/re-Caspase-3 system induced apoptosis in hTERT
      positive cancer cells: CNE1 (nasopharyngeal carcinoma), HRT-18 (colonic
      carcinoma), MGC (stomath carcinoma), but not in hTERT-low Hacat (human normal
      keratinize epithelium) cells. In addition, the growth of s.c. tumors in nude mice
      was suppressed significantly by the treatment with the hTERT/re-Caspase-3 system.
      Results suggested that the telomerase-specific transfer of there-Caspase-3 gene
      may be an effective and promising targeting approach for the treatment of cancer.

PMID- 17172815
TI  - Knockdown of mutant K-ras expression by adenovirus-mediated siRNA inhibits the in
      vitro and in vivo growth of lung cancer cells.
AB  - The ras mutation, which is observed in 20-30% of human nonsmall cell lung cancers
      (NSCLCs), is one of common genetic alterations and has been proposed to be a
      prognostic factor in lung cancer. Oncogene ras appears to be essential for tumor
      progression and maintenance. Several therapeutic agents have been developed to
      inhibit ras, such as FTIs and antisense oligonucleotides. A new tool for blocking
      oncogenes in cancer cells has emerged with the discovery that RNA interference
      can specifically silence expression of endogenous human genes. In the current
      study, we used small interfering RNA (siRNA) directed against mutant K-ras to
      determine the anti-tumor effects of decreasing the levels of this protein in lung
      cancer cell lines. Adenovirus-mediated siRNA (AdH1/siK-ras(V12)) against K
      ras(V12) markedly decreased K-ras(V12) gene expression and inhibited cellular
      proliferation of NSCLC H441 cells that express the relevant mutation (K-ras codon
      12 GGT --> GTT), but produced minimal growth inhibition on NSCLC H1650 cells that
      lack the relevant mutation. Pretreatment with AdH1/siK-ras(V12) completely
      abrogated subcutaneous engraftment of H441 cells, as compared with a 100% tumor
      take in animals that received control vector-treated tumor cells. The in vivo
      effect of AdH1/siK-ras(V12) treatment was further examined by intratumoral
      injections after tumor induction. Pre-existing tumor growth was reduced by 45% by
      a single intratumoral injection. Three or five repeat injections resulted in
      complete tumor regression in eight of ten nude mice. Further, 23.12% of AdH1/siK
      ras(V12) treated H441 cells underwent apoptosis, as compared with 6.13%, and
      8.27% in untreated and control vector-treated cells, respectively. These results
      indicate that adenovirus-mediated siRNA can specifically and efficiently target
      factors whose expression is altered in malignancy and may have the potential as a
      therapeutic modality to treat human lung cancer.

PMID- 17172816
TI  - Transfection of human monocyte-derived dendritic cells with native tumor DNA
      induces antigen-specific T-cell responses in vitro.
AB  - OBJECTIVE: Nucleofection of genomic tumor (Tu) DNA into human monocyte-derived
      dendritic cells (hMoDC) was evaluated for use in producing anti-tumor vaccines
      able to induce effective T-cell specific immune responses. METHODS: Cultured
      hMoDC obtained from HLA-A2+ normal donors were nucleofected with genomic DNA
      extracted from an HLA-A2+gp100+ Mel 526 cell line and 3' end-labeled with
      biotinylated TdT nucleotides or from a genetically-modified Mel 526 expressing
      enhanced green fluorescent protein (EGFP). An Amaxa Nucleofector system was used
      for electroporation. Nucleofected hMoDC were matured in the presence of cytokines
      and examined in ELISPOT assays for the ability to present the gp100(209-217)
      epitope to epitope-specific T cells or to prime autologous naive T cells in
      culture. RESULTS: The nucleofected hMoDC presented gp100 protein to HLA-A2+gp 100
      specific T cells as observed in IFN-gamma ELISPOT assays. Spot formation was
      inhibited by anti-HLA class I and HLA-A2 but not anti-HLA class II antibodies
      (Abs). Tu DNA-nucleofected hMoDC also primed nasmall yi, Ukrainianve autologous
      peripheral blood T cells in culture to develop into Tu-reactive effector cells
      (CTL). These CTL recognized Tu cells which had donated genomic DNA, and these
      responses were MHC class I- and class II-restricted. The CTL recognized shared Tu
      antigens encoded in Tu-derived DNA. CONCLUSION: Nucleofection of hMoDC with
      genomic Tu-derived DNA is a useful strategy for Tu vaccine production: it is
      feasible, does not require Tu epitope isolation, can be used when few Tu cells
      are available, and avoids Tu-induced DC suppression.

PMID- 17172817
TI  - DNA microarrays: tissue removal and processing affects gene expression.

PMID- 17172818
TI  - Differential activity of sulindac metabolites against squamous cell carcinoma of
      the head and neck is mediated by p21waf1/cip1 induction and cell cycle
      inhibition.
AB  - Sulindac sulfide and sulindac sulfone have demonstrated anti-neoplastic and chemo
      preventive activity against various human tumors, but few studies have examined
      the relative effectiveness of these drugs against squamous cell carcinoma of the
      head and neck (SCCHN). These compounds are metabolites of the nonsteroidal anti
      inflammatory drug sulindac and differ in their ability to inhibit cyclooxygenase
      2 (COX-2) enzyme function. Sulindac sulfide (the sulindac metabolite with COX-2
      inhibitory function) demonstrated strong cell growth inhibition as measured by
      MTT and growth assays in UM-SCC-1 and SCC-25 cells, while sulindac sulfone had
      only moderate effect. Growth inhibition by sulindac sulfide was associated with a
      significant increase in percent G cells and activation of caspase-3. Sulindac
      sulfide induced expression of p21wafl/cipl in a dose-dependent fashion, decreased
      cyclin D1 protein levels, and increased Rb hypophosphorylation. p21waf1/cip1
      protein levels increased without a significant increase in wild-type p53,
      suggesting that sulindac sulfide induces a p53-independent pathway regulating
      p2lwafl/ciP1 protein levels in SCCHN. Sulindac sulfide also induced dose
      dependent expression of PPAR-gamma. In contrast, sulindac sulfone did not
      significantly alter apoptosis, cell cycle distribution or G1 checkpoint protein
      expression at doses below 200 microM. These results demonstrate the differential
      activity of sulindac metabolites and support the hypothesis that sulindac sulfide
      induced perturbations in SCCHN cellular proliferation could be regulated both by
      p21waf1/cip1-dependent cytostatic and caspase-dependent cytotoxic pathways.

PMID- 17172819
TI  - Quercetin, Siamois 1 and Siamois 2 induce apoptosis in human breast cancer MDA-mB
      435 cells xenograft in vivo.
AB  - We sought to investigate the apoptosis-inducing activities of quercetin, Siamois
      1, and Siamois 2 against invasive estrogen-receptor negative MDA-MB 435 cells
      xenografted in athymic nude mice. This study clearly demonstrated that these
      compounds exhibited apoptosis-inducing activities in cell culture system.
      Quercetin (20 microg/mL), Siamois 1 (100 microg/mL), and Siamois 2 (200
      microg/mL) can induce apoptotic cell death by 40 +/-5%, 44 +/- 14 %, and 31 +/-
      13 %, respectively. Two-fold of IC50 of these compounds were clearly found to
      induce apoptosis in breast tumor tissue which can be determined by 99mTc-Annexin
      V scintigraphy and histological staining. This is the first report that the
      apoptosis-inducing effects of quercetin, Siamois 1 and Siamois 2 on the MDA-MB
      435 cell in vitro were effectively extrapolated to the in vivo situation. These
      compounds might be considered as a simple dietary supplement and with further
      clinical investigation for their use as a nutrition-based intervention in breast
      cancer treatment.

PMID- 17172820
TI  - Growth inhibitory effects of gastric cancer cells with an increase in S phase and
      alkaline phosphatase activity repression by aloe-emodin.
AB  - Aloe-emodin is a novel active compound found in the root and rhizome of Rheum
      palmatum. To investigate the effects and mechanisms of aloe-emodin on human
      gastric cancer, MGC-803 cells were treated with 2.5, 5, 10, 20 and 40 microM aloe
      emodin for 1-5 d. The results showed that aloe-emodin inhibited the growth of
      cancer cells in a dose-dependent manner with an increase in S phase and in the
      proportion of cells cycling at a higher ploidy level (>G2/M). Moreover, the
      alkaline phosphatase (ALP) activity, an indicator of cell differentiation, was
      found decreased. This is one of the first to focus on the effect of ALP activity
      in human gastric carcinomas cells treated by aloe-emodin. These results indicate
      that aloe-emodin has a potential value for the treatment of gastric cancer and
      its mechanisms are by means of cell cycle interruption and induce
      differentiation.

PMID- 17172821
TI  - Profile of Ets gene expression in human breast carcinoma.
AB  - BACKGROUND: Ets genes encode a family of transcription factors that play key
      roles in cell proliferation, differentiation and apoptosis. Fusions of Ets genes
      with other targets have been described in Ewing's sarcoma, chronic myelomonocytic
      leukemia and more recently prostate carcinoma. Ets expression in breast carcinoma
      has not been comprehensively studied, and is the focus of this study. METHODS: RT
      Q-PCR was used to determine the expression of Ets genes in a panel of ten common
      breast cancer cell lines, two immortalized normal breast epithelial cell lines,
      and one primary culture of human mammary epithelial cells. Ets with altered
      expression in cancer cell lines were verified in primary breast tumors. RESULTS:
      Transcripts of 21 of the 27 Ets genes were detected in either normal or cancer
      cells. Of the 21 detectable genes, 14 were expressed at a similar level in both
      normal and breast cancer cell lines. Four genes, Ehf, Elf3, Elf5 and Pdef, were
      expressed at higher levels in breast cancer cells than normal epithelials.
      Surprisingly, the expression of Elk3, Etsl and Flil was repressed in breast
      cancer cells. The protein status of Ehf, Elf3, Pdef, Elk3, Etsl and Flil,
      strongly correlated with the transcript data, suggesting that Ets expression is
      regulated primarily at the transcriptional level. Similarly, Elf3, Pdef and Tel2
      were overexpressed, while Elk3, Etsl and Flil were under-expressed in primary
      breast tumor specimens in comparison with normal mammary tissues. CONCLUSIONS:
      Our study identified a subset of Ets genes with altered expression in breast
      carcinoma, implicating their roles in mammary tumorigenesis. While the Ets over
      expression pattern is useful to uncover recurrent genetic alterations involving
      Ets genes, the repressed expression of several Ets genes suggests that some Ets
      proteins may play suppressor roles during breast cancer progression. Our results
      warrant detailed studies of individual Ets activity during mammary gland
      neoplasia.

PMID- 17172822
TI  - Expression of TMPRSS2:ERG gene fusion in prostate cancer cells is an important
      prognostic factor for cancer progression.
AB  - The prostate-specific gene, TMPRSS2, is fused with the transcription factor gene,
      ERG in a high proportion of prostate cancers. However, the clinical significance
      of TMPRSS2:ERG gene fusion among prostate cancer patients is unknown. We assayed
      for the presence of the TMPRSS2:ERG gene fusion product among 26 patients who
      underwent surgery for clinically localized prostate cancer using RT-PCR and
      direct DNA sequencing, and evaluated its prognostic significance. All 26 patients
      had cancers of the same histologic grade (Gleason score 7). The fusion protein
      was present within prostate cancer tumor cells in eleven patients (42.3%). Nine
      patients experienced biochemical disease relapse (elevated PSA) after a mean
      follow-up of 12 months (range 1 to 48 months). Patients with the fusion protein
      had a significantly higher rate of recurrence (5-year recurrence rate 79.5%)
      compared to patients who lacked the fusion protein (five-year recurrence rate
      37.5%, p = 0.009). The adjusted hazard ratio for disease relapse for patients
      with the fusion protein was 7.1 (95% C.I.: 1.1-45, p = 0.03) compared to patients
      without the fusion protein. In multivariate analysis, the presence of gene fusion
      was the single most important prognostic factor. Our study indicates that the
      expression of TMPRSS2:ERG fusion gene among prostate cancer patients treated with
      surgery is a strong prognostic factor for disease relapse, and may have important
      clinical implications.

PMID- 17172823
TI  - In vitro comparison of the vitamin D endocrine system in 1,25(OH)2D3-responsive
      and -resistant melanoma cells.
AB  - We studied effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], its analog
      seocalcitol (EB 1089), and 25-hydroxyvitamin D3 [25(OH)D3], on the growth of
      seven melanoma cell lines. While three cell lines (MeWo, SK-Mel-28, SM) responded
      to antiproliferative effects of active vitamin D analogs, the others (SK-Mel-5,
      SK-Mel-25, IGR, MeUuso) were resistant. A strong induction (7000-fold) of 1,25
      dihydroxyvitamin D-24-hydroxylase (24OHase, CYP24) mRNA was detected in
      responsive cell lines along with 1,25(OH)2D3-treatment, indicating functional
      integrity of vitamin D receptor (VDR)-mediated transcription. In contrast,
      induction of 24OHase was much lower in resistant melanoma cells (70-fold). VDR
      mRNA was induced up to 3-fold both in responsive and resistant cell lines along
      with 1,25(OH)2D3-treatment. RNA for vitamin D-activating enzymes vitamin D-25
      hydroxylase (25OHase, CYP27A1) and 25-hydroxyvitamin D-lalpha-hydroxylase
      (lalphaOHase, CYP27B1) was detected in all melanoma cell lines analyzed,
      additionally we show splicing variants of lalphaOHase in SK-Mel-28 cells.
      Expression of 250Hase and laOHase was marginally modulated along with treatment.
      Proliferation of melanoma cells was not inhibited by treatment with 25(OH)D3,
      indicating no significant stimulation of endogeneous production of
      antiproliferative acting 1,25(OH)2D3. In conclusion, we characterize the vitamin
      D endocrine system in melanoma cells and demonstrate that the majority of
      melanoma cell lines analyzed is resistant to antiproliferative effects of
      1,25(OH)2D3. It can be speculated that these alterations are of importance for
      pathogenesis and growth of metastasizing malignant melanoma. Additionally, our
      findings indicate that only a minority of cases with metastasizing melanoma may
      represent a promising target for palliative treatment with new vitamin D analogs
      that exert little calcemic side effects or for pharmacological modulation of
      1,25(OH)2D3-synthesis/metabolism.

PMID- 17172824
TI  - Detecting changes in tumor hypoxia with carbonic anhydrase IX and pimonidazole.
AB  - We have used immunohistochemistry to examine the dynamics of tumor hypoxia..
      Expression of CAIX is known to be influenced by tumor hypoxia, and this protein
      has been shown to be an endogenous hypoxia marker in several models. However, due
      to its long half-life, it could also be present in oxygenated tissue that had
      recently been hypoxic. To investigate this issue we have compared CAIX expression
      to the exogenous hypoxia marker, pimonidazole using HT29 (human colorectal
      cancer) xenografts. We manipulated tumor hypoxia with carbogen and hydralazine,
      treatments that respectively increased and decreased tumor oxygenation. (Carbogen
      was given 75 minutes and hydralazine 30 minutes before sacrifice). In tumors from
      the control group, CAIX and pimonidazole exhibited similar (though not identical)
      spatial distribution, and for both markers, the fraction of the section staining
      positively was similar (13.2% and 12.6% respectively). The mice treated with
      hydralazine showed a significant increase in pimonidazole accumulation (37.2%, p
      = 0.03), though the CAIX positive fraction was unchanged (14.2%). In contrast, in
      the carbogen group pimonidazole staining decreased to 3% (p = 0.01) though CAIX
      expression was again unaltered. These results suggest that comparison of CAIX and
      pimonidazole will allow for the detection of reoxygenation.

PMID- 17172825
TI  - Histone deacetylase inhibitor LBH589 reactivates silenced estrogen receptor alpha
      (ER) gene expression without loss of DNA hypermethylation.
AB  - Our previous studies demonstrated that inhibition of histone deacetylases (HDACs)
      by trichostatin A reactivates estrogen receptor alpha (ER) gene expression in ER
      negative breast cancer cells. Here, we use the clinically relevant HDAC
      inhibitor, LBH589 (LBH) to explore the roles of HDAC in ER gene silencing. In the
      ER-negative human breast cancer lines, MDA-MB-231 and MDA-MB-435, treatment with
      LBH for 24 hours restored ER mRNA and protein expression without a concomitant
      demethylation of the CpG island at the ER promoter. The expression of ER mRNA was
      sustained at least 96 hours after withdrawal of LBH treatment. Restoration of ER
      expression by LBH enhanced 4-hydroxy-tamoxifen sensitivity in MDA-MB-231 cells.
      The molecular mechanisms by which LBH reactivated silenced ER gene in MDA-MB-231
      cells were examined with emphasis on chromatin structure reorganization. By
      chromatin immunoprecipitation analysis, LBH treatment released DNMT1, HDAC1, and
      the H3 lysine 9 (H3-K9) methyltransferase SUV39H 1 from the ER promoter. Such
      changes were associated with an active chromatin formation manifested as
      accumulation of acetylated histones H3 and H4, a decrease in methylated H3-K9,
      and an impaired binding of heterochromatin protein 1 (HP1 alpha) at the promoter.
      Our findings suggest that HDAC inhibitors could restore expression of the
      silenced ER gene by reorganizing the heterochromatin-associated proteins without
      alteration in promoter DNA hypermethylation.

PMID- 17172826
TI  - PPARgamma ligands enhance TRAIL-induced apoptosis through DR5 upregulation and c
      FLIP downregulation in human lung cancer cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands are
      potential chemo-preventive agents. Many studies have shown that PPARy ligands
      induce apoptosis in various types of cancer cells including lung cancer cells.
      Some PPAR gamma ligands have been shown to downregulate c-FLIP expression and
      thus enhance tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      induced apoptosis in some cancer cell lines. In the current study, we further
      show that PPARy ligands induced the expression of death receptor 5 (DR5) and
      increased DR5 distribution at the cell surface in addition to reducing c-FLIP
      levels in human lung cancer cells. These agents cooperated with TRAIL to enhance
      induction of apoptosis in human lung cancer cells. Both overexpression of c-FLIP
      and knockdown of DR5 abrogated PPARgamma ligand's ability to enhance TRAIL
      induced apoptosis. Thus, it appears that not only c-FLIP downregulation but also
      DR5 upregulation contribute to PPARy ligand-mediated enhancement of TRAIL-induced
      apoptosis in human lung cancer cells. Both the PPARgamma antagonist GW9662 and
      silencing PPARgamma expression failed to diminish PPARgamma ligand-induced DR5
      upregulation or c-FLIP downregulation, indicating that PPARy ligands modulate the
      expression of DR5 and c-FLIP through a PPARy-independent mechanism. Collectively,
      we conclude that PPARy ligands exert PPARy-independent effects on inducing DR5
      expression and downregulating c-FLIP levels, leading to enhancement of TRAIL
      induced apoptosis.

PMID- 17172827
TI  - The role of MYCN in the failure of MYCN amplified neuroblastoma cell lines to G1
      arrest after DNA damage.
AB  - We previously reported that 3 p53 wild type (wt) MYCN amplified (MNA)
      neuroblastoma cell lines failed to G1 arrest after DNA damage despite induction
      of p53, p21(WAF1) and MDM2. We hypothesised that this was due to high MYCN
      expression. p53 responses to DNA damage were examined in an additional 13 p53 wt
      neuroblastoma cell lines. MNA was significantly associated with a failure to G1
      arrest after DNA damage (p < 0.001) and higher levels of apoptosis after
      irradiation (p < 0.05). p21(WAF1) and hypophosphorylated (hypo) RB accumulation
      post irradiation were significantly lower in cell lines that failed to G1 arrest
      (p < 0.05). Conditional MYCN expression in non-MNA SHEP Tet21N cells did not
      affect the G1 arrest after irradiation. MYCN knockdown using siRNA in 3 p53 wt
      MNA cell lines did not restore a G1 arrest after irradiation, but increased the
      baseline G1 population, p21(WAF1) and hypo RB expression. MYCN siRNA also caused
      a G1 arrest in a p53 mutant MNA cell line. This study is the first to determine
      that MNA correlates with a failure to G1 arrest and attenuated p21(WAF1)
      induction; however MYCN expression alone is not causally responsible.

PMID- 17172828
TI  - A cytoplasmic PML mutant inhibits p53 function.
AB  - The promyelocytic leukaemia gene (Pml) is a tumor suppressor identified in acute
      promyelocytic leukaemia (APL), where it is fused to RAR alpha gene as a result of
      the chromosomal translocation t(15;17). Pml encodes both nuclear and cytoplasmic
      isoforms. While nuclear PML has been intensively investigated, cytoplasmic PML
      proteins are less characterized. PML nuclear isoforms (nPML) are the essential
      components of subnuclear structures referred to as PML nuclear bodies (PML-NB).
      In response to cellular insults such as DNA damage and oncogenic activation, nPML
      modulates p53 activity through CBP-mediated acetylation and activates its pro
      apoptotic and growth suppressive functions. Two missense mutations resulting in
      truncated PML cytoplasmic proteins (Mut PML) have been identified in aggressive
      APL cases. Here we report that cytoplasmic PML is able to induce the relocation
      of nPML to the cytoplasm, thus reducing the number of PML-NBs. Remarkably, Mut
      PML inhibits p53 transcriptional, growth suppressive, and apoptotic functions,
      thus suggesting that cytoplasmic expression of PML has an impact on survival
      through inhibition of nuclear PML. Overall our findings shed new light on the
      role of PML cytoplasmic proteins in the regulation of p53.

PMID- 17172829
TI  - A stress response pathway involving sirtuins, forkheads and 14-3-3 proteins.
AB  - A conserved sir2 deacetylase gene can determine longevity of yeast, flies and
      worms. Recently we have reported a molecular mechanism of action of the C.
      elegans homologue sir-2.1. Our study revealed a novel stress-dependent pathway
      for lifespan determination in which SIR-2.1 binds to 14-3-3 proteins and a
      forkhead transcription factor DAF-16 to activate transcription of DAF-16 target
      genes. DAF-16 has long been known as a central protein in the regulation of
      lifespan that interfaces with multiple pathways. Recent studies by us and other
      laboratories suggest that DAF-16 requires co-factors for full activity. In this
      prospective we review recent literature highlighting the role of SIR-2.1, 14-3-3
      and other DAF-16 co-factors in DAF-16 activation.

PMID- 17172830
TI  - BRIT1/MCPH1: a guardian of genome and an enemy of tumors.
AB  - The DNA of every cell is constantly exposed to insult mediated by endogenous and
      environmental factors that induced damage in its structure. To react to these
      attacks and maintain the integrity of the genome, eukaryotic cells are equipped
      with sophisticated mechanisms to detect, signal the presence of and repair DNA
      damage. The cellular response to DNA damage is a critical event for maintaining
      genomic stability and limiting neoplastic transformation. BRIT1, a newly
      identified protein, forms specific irradiation-induced nuclear foci. Our recent
      investigation demonstrates that BRIT1 functions as a proximal factor in the DNA
      damage checkpoints that control multiple damage sensors and early mediators.
      BRIT1 is also implicated in cell cycle checkpoints, controlling and regulating
      other important molecules and thus affecting the timing of mitosis. Depletion of
      BRIT1 abolishes the DNA damage response and results in centrosomal abnormalities
      and chromosomal aberrations. Moreover, aberrantly reduced expression of BRIT1 in
      human carcinomas implicates this protein in cancer initiation and progression.
      Together, the findings identify BRIT1 as a potential tumor suppressor. Fully
      elucidating the function of this intriguing protein may lead to new therapeutic
      approaches for the improved cancer treatment.

PMID- 17172831
TI  - Wnt/Wingless pathway activation and chromosome 6 loss characterize a distinct
      molecular sub-group of medulloblastomas associated with a favorable prognosis.
AB  - The accurate assessment of disease risk remains a major goal in children with
      medulloblastoma. Activation of the canonical Wnt/Wingless (Wnt/Wg) signalling
      pathway occurs in up to 25% of cases and is associated with a favorable disease
      outcome. To explore the molecular pathogenesis of Wnt/Wg-active medulloblastomas,
      and to investigate any genetic basis for their observed clinical behavior, we
      assessed a series of primary medulloblastomas for evidence of Wnt/Wg pathway
      activation, alongside a genome-wide analysis of associated copy-number
      aberrations. Cases displaying evidence of Wnt/Wg activation (CTNNB1 mutation
      and/or beta-catenin nuclear stabilisation) were exclusively associated with a
      distinct genomic signature involving loss of an entire copy of chromosome 6 but
      few other aberrations (p < 0.001). In contrast, Wnt/Wg-negative tumors
      coclustered into an unrelated sub-group characterised by multiple established
      genomic defects common in medulloblastoma (losses of chromosomes 17p, 8, 10 and
      16; gains of chromosomes 7 and 17q). Further investigation of specific genetic
      defects in a larger independent cohort demonstrated that loss of chromosome 6 was
      exclusively observed in Wnt/Wg-active tumors, but not in Wnt/Wg-negative cases
      (8/13 vs. 0/19; p = 0.0001), while pathway activation was independent of
      chromosome 17 aberrations, the most common chromosomal alterations detected in
      medulloblastoma (p = 0.005). Wnt/Wg-active tumors could not be distinguished on
      the basis of clinical or pathological disease features. Our data indicate that
      Wnt/Wg-active tumors represent an independent molecular sub-group of
      medulloblastomas characterised by a distinct pattern of genomic aberrations.
      These findings provide a strong biological basis to support (1) the idiosyncratic
      clinical behavior of Wnt/Wg-active medulloblastomas, and (2) the development of
      beta-catenin status as an independent marker for therapeutic stratification in
      this disease.

PMID- 17172832
TI  - The role of Vpr in the regulation of HIV-1 gene expression.
AB  - Expression of the viral protein R, Vpr, of HIV-1 affects many biological events
      in host cells including cell cycle progression, and modulates HIV-1 gene
      transcription. Earlier studies implicating the cellular protein p21(WAF1) (p21)
      in regulation of HIV-1 transcription, led us to investigate the functional and
      physical interaction of Vpr and p21. Our results show that Vpr modestly activated
      HIV-LTR in cells lacking p21 gene. Here, we describe the mechanisms by which p21
      and Vpr leading to stimulation of HIV-1 transcription. Data from the protein
      protein interaction experiments revealed the ability of Vpr, p21 and p300 to form
      a complex. Further, we show that, Vpr interacts with the N- and the C-terminal
      domains of p21. Furthermore, in cells expressing Vpr, p21 localizes to both the
      cytoplasm and the nucleus. Interestingly, expression of Vpr alleviates p21
      mediated inhibition of cell departure from G1 phase. Expression of a mutant Vpr,
      with arginine 73 altered to serine, did not affect the ability of p21 to cause
      cells arrest or its sub-cellular localization. These observations reveal a new
      cellular partner for Vpr, and provide a new therapeutic avenue for controlling
      HIV-1 expression.

PMID- 17172833
TI  - Aurora B kinase maintains chromatin organization during the MI to MII transition
      in surf clam oocytes.
AB  - Meiosis represents a specialized cell cycle whereby cells undergo two reductive
      divisions without an intervening S phase. In oocytes, the transition from meiosis
      I to II is brief, with paired sister chromatids remaining condensed throughout
      the interkinesis period. This stands in contrast to mitotic divisions where
      cytokinesis and the return to interphase is always accompanied by chromatin
      decondensation and nuclear envelope reformation. Because other aspects of M phase
      exit are normal, we probed the mechanisms that allow for polar body extrusion
      while retaining chromatin condensation in Spisula solidissima oocytes. If oocytes
      were activated in the presence of protein synthesis inhibitors, oocytes
      progressed normally through MI, but arrested in interkinesis with condensed
      chromatin, phosphorylated histone H3 and a disorganized MII spindle. Neither
      inhibition of CDK1- nor MAPK activity in arrested oocytes was sufficient to drive
      chromatin decondensation or nuclear envelope reformation, suggesting that these
      kinases were not responsible for the maintenance of chromatin condensation.
      However, inhibition of Aurora B kinase activity resulted in chromatin
      decondensation, loss of histone H3 phosphorylation and reformation of the nuclear
      envelope. Inhibition of Aurora B activity following MI also resulted in
      chromosome segregation defects during MII and blocked polar body formation,
      consistent with Aurora B's well-established role in cytokinesis. Together, these
      results suggest that extended Aurora B activity between meiotic divisions
      maintains chromatin condensation, thus allowing for the rapid reassembly of the
      MII spindle and progression through meiosis.

PMID- 17172834
TI  - Integration of HapMap-based SNP pattern analysis and gene expression profiling
      reveals common SNP profiles for cancer therapy outcome predictor genes.
AB  - Recent completion of the initial phase of a haplotype map of human genome
      (www.hapmap.org) provides opportunity for integrative analysis on a genome-wide
      scale of microarray-based gene expression profiling and SNP variation patterns
      for discovery of cancer-causing genes and genetic markers of therapy outcome.
      Here we applied this approach for analysis of SNPs of cancer-associated genes,
      expression profiles of which predicts the likelihood of treatment failure and
      death after therapy in patients diagnosed with multiple types of cancer.
      Unexpectedly, this analysis reveals a common SNP pattern for a majority (60 of
      74; 81%) of analyzed cancer treatment outcome predictor (CTOP) genes. Our
      analysis suggests that heritable germ-line genetic variations driven by
      geographically localized form of natural selection determining population
      differentiations may have a significant impact on cancer treatment outcome by
      influencing the individual's gene expression profile. We demonstrate a
      translational utility of this approach by building a highly informative CTOP
      algorithm combining prognostic power of multiple gene expression-based CTOP
      models derived from signatures of oncogenic pathways associated with activation
      of BMI1; Myc; Her2/neu; Ras; beta-catenin; Suz12; E2F; and CCND1 oncogenes.
      Application of a CTOP algorithm to large databases of early-stage breast and
      prostate tumors identifies cancer patients with 100% probability of a cure with
      existing cancer therapies as well as patients with nearly 100% likelihood of
      treatment failure, thus providing a clinically feasible framework essential for
      introduction of rational evidence-based individualized therapy selection and
      prescription protocols. Our analysis indicates that genetic determinants of human
      disease susceptibility and severity are encoded by population differentiation SNP
      variants. Evolution of these SNPs is driven by geographically-localized form of
      natural selection causing population differentiation. Recent analysis identifies
      a class of SNPs regulating gene expression in normal individuals and likely
      determining unique genome-wide expression profiles of each individual. We propose
      that critical disease-causing combinations of SNP variants arise from SNPs
      regulating mRNA levels and determining genome-wide haplotype patterns of
      individual's disease susceptibility.

PMID- 17172835
TI  - How might DNA enter the cohesin ring?

PMID- 17172836
TI  - Regulation, cell differentiation and protein-based inheritance.
AB  - Recent research using fungi as models provide new insight into the ability of
      regulatory networks to generate cellular states that are sufficiently stable to
      be faithfully transmitted to daughter cells, thereby generating epigenetic
      inheritance. Such protein-based inheritance is driven by infectious factors
      endowed with properties usually displayed by prions. We emphasize the
      contribution of regulatory networks to the emerging properties displayed by
      cells.

PMID- 17172837
TI  - Modulating molecular functions of p53 with small molecules.
AB  - Association of the human tumor suppressor p53 with many human cancers makes it a
      valuable therapeutic target. Stress-induced molecular interactions of p53 with
      other effector proteins are immensely intertwined with regulation of its
      functions in orchestrating a wide array of cellular responses, thereby defying
      analysis of the underlying molecular mechanisms with conventional molecular and
      cellular biology methods. Recent discoveries of small molecules that can
      selectively modulate the molecular interactions of p53 offer promising
      opportunities to address the challenge of dissecting these complex mechanisms and
      increase the hope for pharmacological control of p53 for clinical benefits of
      cancer patients.

PMID- 17172838
TI  - Histone H3 lysine 56 acetylation: a new twist in the chromosome cycle.
AB  - Several recent reports have identified lysine 56 (K56) as a novel site of
      acetylation in yeast histone H3. K56 acetylation is predicted to disrupt some of
      the histone-DNA interactions at the entry and exit points of the nucleosome core
      particle. This modification occurs in virtually all the newly synthesised
      histones that are deposited into chromatin during S-phase. Cells with mutations
      that block K56 acetylation show increased genome instability and hypersensitivity
      to genotoxic agents that interfere with replication. Removal of K56 acetylation
      takes place in the G2/M phase of the cell cycle and is dependent upon Hst3 and
      Hst4, two proteins that are related to the NAD+-dependent histone deacetylase
      Sir2. In response to DNA damage checkpoint activation during S-phase, expression
      of Hst3/Hst4 is delayed to extend the window of opportunity in which K56
      acetylation can act in the DNA damage response. The high abundance of histone H3
      K56 acetylation, its regulation and strategic location in the nucleosome core
      particle raise a number of fascinating issues that we discuss here.

PMID- 17172839
TI  - Pathophysiology defined by altered signal transduction pathways: the role of JAK
      STAT and PI3K signaling in leukemic large granular lymphocytes.
AB  - Signal transduction pathways integrate a variety of microenvironmental cues to
      guide cell function by regulating gene transcription, cell cycle status, growth,
      and differentiation. It is well established that perturbation of these processes
      plays a key role in hematologic malignancies including lymphomas and chronic and
      acute lymphocytic leukemias. Altered intracellular signaling pathways have been
      proposed to mediate many biological properties of T cell large granular
      lymphocytic leukemia (T-LGL), a disorder characterized by a clonal proliferation
      of CD8 T cells resulting in immune-mediated cytopenias, most commonly
      neutropenia. Since T-LGL offers a unique opportunity to study signal transduction
      in the pathologic clonal cytotoxic T cell (CTL) compared to normal CTL, we have
      investigated a potential imbalance in T-LGL pro-survival signaling to define the
      mechanisms underlying the semi-autonomous proliferation leading to leukemia.
      Increased activity of the PI3K-AKT signaling axis in T-LGL cells appears to
      operate in conjunction with or parallel to increased STAT3 activation in these
      cells to inhibit the apoptotic program. Thus, the ability to define
      pathophysiology at the molecular level opens new avenues for targeted
      therapeutics.

PMID- 17172840
TI  - Inhibition of PI3K induces Rac activation and membrane ruffling in proto-Dbl
      expressing cells.
AB  - Proto-Dbl protein, a guanine nucleotide exchange factor (GEF) for Rho GTPases, is
      tightly regulated by a combination of mechanisms that involve intra- and
      intermolecular interaction and N- and C-terminal domain-dependent turnover of the
      protein. Moreover, the interaction of the PH domain of proto-Dbl with
      phosphoinositides regulates its subcellular localization and biological activity.
      Here we show that inhibition of the phosphatidylinositol 3-kinase (PI3K) by
      molecular and pharmacological inhibitors causes a strong inhibition of proto-Dbl
      induced cell proliferation and transformation. Conversely, inhibition of PI3K
      results in the translocation of proto-Dbl to the plasma membrane, Rac activation
      and increased membrane ruffles and cell motility. Furthermore, we investigated
      the signaling molecules involved in proto-Dbl-induced cell transformation and
      motility and observed that inhibition of PI3K in proto-Dbl expressing cells
      induces an increase in p38 activity and a decrease in ERK phosphorylation. Our
      results suggest that proto-Dbl activates distinct downstream effectors to induce
      morphological changes and cell transformation.

PMID- 17172841
TI  - Cell cycle synchronization at the G2/M phase border by reversible inhibition of
      CDK1.
AB  - Chemical agents for cell cycle synchronization have greatly facilitated the study
      of biochemical events driving cell cycle progression. G1, S and M phase
      inhibitors have been developed and used widely in cell cycle research. However,
      currently there are no effective G2 phase inhibitors and synchronization of
      cultured cells in G2 phase has been challenging. Recently, a selective CDK1
      inhibitor, RO-3306, has been identified that reversibly arrests proliferating
      human cells at the G2/M phase border and provides a novel means for cell cycle
      synchronization. A single-step protocol using RO-3306 permits the synchronization
      of >95% of cycling cancer cells in G2 phase. RO-3306 arrested cells enter mitosis
      rapidly after release from the G2 block thus allowing for isolation of mitotic
      cells without microtubule poisons. RO-3306 represents a new molecular tool for
      studying CDK1 function in human cells.

PMID- 17172842
TI  - Expression of EWS-ETS fusions in NIH3T3 cells reveals significant differences to
      Ewing's sarcoma.
AB  - Ewing's sarcomas contain specific chromosomal translocations that fuse EWS to ETS
      family members, including FLI, ERG, FEV, ETV1 and ETV4. Prior work has suggested
      that functional differences exist between some of these EWS-ETS fusions. However,
      as the cell of origin of Ewing's sarcoma is unknown, this prior work was
      conducted in NIH3T3 cells, which have not been validated as an appropriate model
      for the study of EWS-ETS fusions. To determine if NIH3T3 cells are a good model
      for Ewing's sarcoma, we introduced all five EWS-ETS fusions into these cells, and
      analyzed their phenotypes and gene expression patterns. EWS-FLI, EWS-ERG, and EWS
      FEV caused NIH3T3 cells to exhibit anchorage independent growth whereas EWS-ETV1
      and EWS-ETV4 did not. In contrast, all the EWS-ETS fusions induced tumor
      formation in a xenograft model. We defined the core transcriptional profile of
      the EWS-ETS fusions using cDNA microarrays, and compared these to data derived
      from patient-derived Ewing's sarcoma cell lines. The NIH3T3 model did not
      recapitulate the gene expression pattern of bona fide Ewing's sarcoma. Based on
      these results, we conclude that while there may be functional differences between
      the various EWS-ETS fusions, the NIH3T3 cell model is inadequate to study the
      gene expression pattern induced by EWS-ETS proteins in Ewing's sarcoma. Thus,
      data derived from the NIH3T3 model system needs to be appropriately validated
      before they can be accepted as relevant to the human disease.

PMID- 17172843
TI  - The association of Tap42 phosphatase complexes with TORC1: another level of
      regulation in Tor signaling.
AB  - In the budding yeast Saccharomyces cerevisiae, rapamycin has been known to induce
      a rapid dephosphorylation of many downstream targets of Tor. The key components
      mediating this dephosphorylation process are the Tap42-associated phosphatases,
      which become active upon rapamycin treatment. However, the mechanism by which
      rapamycin rapidly activates phosphatases is unclear. A recent report has provided
      evidence demonstrating a physical association of the Tap42-phosphatase complexes
      with TORC1, which is sensitive to rapamycin treatment or nutrient starvation.
      This association adds another level of regulation in Tor signaling, and explains
      why rapamycin or nutrient availability is able to initiate a rapid and robust
      response in the cell.

PMID- 17172844
TI  - Ser46 phosphorylation regulates p53-dependent apoptosis and replicative
      senescence.
AB  - Posttranslational modification such as phosphorylation of p53 plays important
      roles in activating p53 responses to various cellular and genotoxic stresses.
      Cell line studies have shown that phosphorylation of Ser46 is correlated with the
      activation of p53 apoptotic activity. To address the physiological roles of Ser46
      phosphorylation, we employed homologous recombination and LoxP/Cre-mediated
      deletion to introduce Ser46 to Ala missense mutation into the human p53 knock-in
      (HUPKI) allele in mice (p53hki(S46A)). p53 stabilization in response to various
      types of DNA damage is modestly reduced in p53hki(S46A) embryonic stem (ES)
      cells, mouse embryonic fibroblasts (MEFs) and thymocytes. In addition, p53
      dependent apoptosis is partially impaired in p53hki(S46A) thymocytes and E1A/Ras
      expressing mouse embryonic fibroblasts (MEFs) after DNA damage. Consistent with
      this finding, transcription of p53 target apoptotic genes is preferentially
      affected by S46A mutation after DNA damage. p53hki(S46A) MEFs proliferate and
      reach senescence normally but can be spontaneously immortalized more easily than
      wild type MEFs. In addition, p53hki(S46A) MEFs more readily escapes from Ras
      induced senescence. Therefore, Ser46 phosphorylation activates p53-dependent
      apoptosis induced by DNA damage and cellular senescence induced by oncogenic
      stress.

PMID- 17172845
TI  - Structural basis for the modulation of CDK-dependent/independent activity of
      cyclin D1.
AB  - D-type cyclins are key regulators of the cell division cycle. In association with
      Cyclin Dependent Kinases (CDK) 2/4/6, they control the G1/S-phase transition in
      part by phosphorylation and inactivation of tumor suppressor of retinoblastoma
      family. Defective regulation of the G1/S transition is a well-known cause of
      cancer, making the cyclin D1-CDK4/6 complex a promising therapeutic target. Our
      objective is to develop inhibitors that would block the formation or the
      activation of the cyclin D1-CDK4/6 complex, using in silico docking experiments
      on a structural homology model of the cyclin D1-CDK4/6 complex. To this end we
      focused on the cyclin subunit in three different ways: (1) targeting the part of
      the cyclin D1 facing the N-terminal domain of CDK4/6, in order to prevent the
      dimer formation; (2) targeting the part of the cyclin D1 facing the C-terminal
      domain of CDK4/6, in order to prevent the activation of CDK4/6 by blocking the T
      loop in an inactive conformation, and also to destabilize the dimer; (3)
      targeting the groove of cyclin D1 where p21 binds, in order to mimic its
      inhibition mode by preventing binding of cyclin D1-CDK4/6 complex to its targets.
      Our strategy, and the tools we developed, will provide a computational basis to
      design lead compounds for novel cancer therapeutics, targeting a broad range of
      proteins involved in the regulation of the cell cycle.

PMID- 17172847
TI  - Depletion of histone deacetylase protein: a common consequence of inflammatory
      cytokine signaling?
AB  - The dynamics of histone acetylation and deacetylation have long been known to
      influence gene expression by cellular signaling pathways. However, the mechanisms
      that regulate histone acetyl transferases (HATs) and histone deacetylases (HDACs)
      by these pathways have only recently become the focus of scientific
      investigation, spurred by increasing knowledge that HDACs can promote cancer
      growth. We recently reported that pro-inflammatory signals such as tumor necrosis
      factor alpha (TNFalpha) induce HDAC1 ubiquitination and proteasomal degradation
      through the IkappaB kinase IKKbeta. The resulting depletion of cellular HDAC1
      levels lead to a consequent depletion of HDAC1 associated with the CDKN1A gene
      promoter and increased expression of its protein product, p21(WAF1/CIP1). This
      phenomenon heralds a unique mechanism of HDAC regulation that modulates the pro
      inflammatory activity of TNFalpha and other cytokines at the level of gene
      expression. Here we discuss the current knowledge of pro-inflammatory cytokine
      induced regulation of gene expression, emphasizing the involvement of HDAC1, and
      its possible implications in inflammation, cancer, and their therapy.

PMID- 17172846
TI  - EGF induces cell motility and multi-drug resistance gene expression in breast
      cancer cells.
AB  - The epidermal growth factor receptor (EGFR) is important for normal development,
      differentiation, and cell proliferation. Deregulation of EGFR has been observed
      in breast cancer. EGFR and signal pathways activated by these receptors have been
      associated with an advanced tumor stage and a poor clinical prognosis in breast
      cancer; however, the precise mechanisms responsible for this process are still
      not known. Here we show that treatment of MCF-7 breast cancer cells with EGF
      activated Akt and ERK, induced morphological changes, and increased cell
      motility. In addition, the constitutive expression of Raf-1 and the use of a MEK
      inhibitor demonstrated the participation of the Raf/MEK/ERK pathway in these
      processes. Importantly we detected that EGF induced MRP-1, 3, 5 and 7 gene
      expression and an increase in MRP1 promoter activity. In conclusion, treatment of
      MCF-7 breast cancer cells with EGF, in the absence of other growth factors,
      resulted in activation of EGFR signal transduction pathways; which were related
      with cell motility and drug resistance.

PMID- 17172848
TI  - FGFR3 mutations in benign skin tumors.
AB  - Activating FGFR3 germline mutations cause skeletal dysplasia and craniosynostosis
      syndromes. Somatic FGFR3 mutations have been identified in several cancer
      entities such as urothelial carcinoma and multiple myeloma. Recently, the same
      FGFR3 mutations known from skeletal dysplasia syndromes and urothelial carcinoma
      have been shown to cause benign human skin tumors such as seborrheic keratoses
      and epidermal nevi. The underlying mechanisms for the somatic FGFR3 mutations in
      the epidermis are unknown so far, as well as details of the involved signaling
      pathways in the mutant keratinocytes leading to the formation of acanthotic skin
      tumors. Herein we discuss potential mechanisms and functional consequences of
      activating FGFR3 mutations in human skin. Further studies are required to provide
      insights in the pathogenesis of benign skin tumors caused by FGFR3 mutations.
      These studies will add to new non-invasive therapeutical strategies for benign
      acanthotic skin tumors in dermatology.

PMID- 17172849
TI  - Mapping cellular routes of Ras: a ubiquitin trail.
AB  - The three mammalian Ras isoforms: HRas, NRas and KRas have been widely implicated
      in the control of cell proliferation, survival, motility and transformation.
      Although nearly identical with respect to their catalytic and effector-binding
      properties, HRas, NRas and KRas lead to different biological outcomes in
      development, cell growth and cancer. This functional distinction is believed to
      result at least in part from the differential membrane compartmentalization of
      Ras isoforms. The different distribution of Ras proteins in cellular membranes
      dictates unique spatio-temporal patterns of activation of effector pathways. This
      perspective focuses on the factors that control membrane compartmentalization of
      Ras with an emphasis on a recently discovered novel posttranslational
      modification of Ras--ubiquitination. The properties of Ras ubiquitination, its
      contribution to the regulation of Ras intracellular trafficking and finally the
      influence of Ras ubiquitination on its signaling potential are discussed.

PMID- 17172850
TI  - Motors and their tethers: the role of secondary binding sites in processive
      motility.
AB  - Cytoskeletal motors convert the energy from binding and hydrolyzing ATP into
      conformational changes that direct movement along a cytoskeletal polymer
      substrate. These enzymes utilize different mechanisms to generate long-range
      motion on the order of a micron or more that is required for functions ranging
      from muscle contraction to transport of growth factors along a nerve axon.
      Several of the individual cytoskeletal motors are processive, meaning that they
      have the ability to take sequential steps along their polymer substrate without
      dissociating from the polymer. This ability to maintain contact with the polymer
      allows individual motors to move cargos quickly from one cellular location to
      another. Many of the processive motors have now been found to utilize secondary
      binding sites that aid in motor processivity.

PMID- 17172851
TI  - Concomitant inhibition of MDM2 and Bcl-2 protein function synergistically induce
      mitochondrial apoptosis in AML.
AB  - Disruption of Mdm2-p53 interaction activates p53 signaling, disrupts the balance
      of antiapoptotic and proapoptotic Bcl-2 family proteins and induces apoptosis in
      acute myeloid leukemia (AML). Overexpression of Bcl-2 may inhibit this effect.
      Thus, functional inactivation of antiapoptotic Bcl-2 proteins may enhance
      apoptogenic effects of Mdm2 inhibition. We here investigate the potential
      therapeutic utility of combined targeting of Mdm2 by Nutlin-3a and Bcl-2 by ABT
      737, recently developed inhibitors of protein-protein interactions. Nutlin-3a and
      ABT-737 induced Bax conformational change and mitochondrial apoptosis in AML
      cells in a strikingly synergistic fashion. Nutlin-3a induced p53-mediated
      apoptosis predominantly in S and G2/M cells, while cells in G1 were protected
      through induction of p21. In contrast, ABT-737 induced apoptosis predominantly in
      G1, the cell cycle phase with the lowest Bcl-2 protein levels and Bcl-2/Bax
      ratios. In addition, Bcl-2 phosphorylation on Ser70 was absent in G1 but
      detectable in G2/M, thus lower Bcl-2 levels and absence of Bcl-2 phosphorylation
      appeared to facilitate ABT-737-induced apoptosis of G1 cells. The complementary
      effects of Nutlin-3a and ABT-737 in different cell cycle phases could, in part,
      account for their synergistic activity. Our data suggest that combined targeting
      of Mdm2 and Bcl-2 proteins could offer considerable therapeutic promise in AML.

PMID- 17172852
TI  - Studying the right cell in acute myelogenous leukemia: dynamic changes of
      apoptosis and signal transduction pathway protein expression in chemotherapy
      resistant ex-vivo selected "survivor cells".
AB  - We hypothesized that studying protein expression in cells surviving in vitro
      chemotherapy ("survivor cells", SV), could provide more important insight into
      the biology of drug-resistant AML cells than analysis of the bulk population of
      leukemic cells. Leukemia-enriched samples from 79 patients with new or relapsed
      AML were cultured for four days +/- cytarabine (5-10 microM). Early apoptotic
      cells were removed to yield purified SV. Expression of BCL2, bax, PKC alpha, ERK2
      and pERK2 proteins was measured using laser scanning cytometry. The SV population
      was enriched for CD34+ stem cells. Protein expression patterns in SV differed
      considerably from those in controls; culture and reanalysis of protein expression
      revealed stability, reversion, or new patterns of change. Patterns of pairs or
      triads of proteins were nonrandomly distributed and appeared at statistically
      unlikely frequencies, suggesting preferential adoption of certain patterns. The
      patterns of change were highly predictive of remission attainment, relapse, and
      survival in univariate and multivariate analysis. We conclude that in vitro SV
      cells have protein expression patterns distinct from those of the bulk population
      of leukemic cells and that these patterns are predictive of outcome. Analysis of
      SV cells may be more informative than analysis of the bulk population of leukemia
      cells.

PMID- 17172853
TI  - Senescence, wound healing and cancer: the PAI-1 connection.
AB  - Prolonged propagation of primary diploid fibroblasts in culture activates an
      ageing process known as replicative senescence, which is considered to provide a
      barrier against oncogenic transformation. Remarkably, both cell autonomous tumor
      suppressive and cell nonautonomous tumor-promoting effects of senescent cells
      have been reported. Recently, we described that the p53 target gene plasminogen
      activator inhibitor-1 (PAI-1) is an essential mediator of replicative senescence.
      PAI-1 antagonizes the protease urokinase-type plasminogen activator (uPA). Both
      are secreted factors and involved in heterotypic signaling processes such as
      wound healing, angiogenesis and metastasis. Both uPA and PAI-1 are expressed in
      senescent cells and their relative abundance controls proliferation downstream of
      p53. Here, we present data that the effects of PAI-1 and uPA in the senescence
      response are not strictly cell autonomous. We discuss these findings in the
      context of the emerging roles of PAI-1 and uPA in heterotypic cellular signaling
      in senescence, wound healing and metastasis.

PMID- 17172854
TI  - Genome maintenance and mutagenesis in embryonic stem cells.
AB  - Widespread loss of heterozygosity (LOH) in cancer cells is often thought to
      result from chromosomal instability caused by mutations affecting DNA
      repair/genome maintenance; however, the origin of LOH in most tumors is unknown.
      In a recent study, we examined the ability of carcinogenic agents to induce LOH
      in diploid mouse embryo-derived stem (ES) cells. Brief exposures to nontoxic
      levels of several carcinogens stimulated genome-wide LOH, with maximum per-gene
      frequencies approaching one percent. These results suggest that LOH contributes
      significantly to the carcinogenicity of a variety of mutagens, and that genome
      wide LOH may result from prior exposure to genotoxic agents rather than from a
      state of chromosomal instability during the carcinogenic process. Mechanisms in
      stem cells that influence carcinogen-induced LOH are likely to play central roles
      in the etiology of nonhereditary cancers that often arise after extensive
      carcinogen exposures.

PMID- 17172855
TI  - Human PIF helicase is cell cycle regulated and associates with telomerase.
AB  - The evolutionarily conserved PIF1 DNA helicase family is important for the
      maintenance of genome stability in the yeast, Saccharomyces cerevisiae. There are
      two PIF1 family helicases in S. cerevisiae, Pif1p and Rrm3p that both possess 5'-
      >3' DNA helicase activity but maintain unique functions in telomerase regulation
      and semi-conservative DNA replication. Database analysis shows that the PIF1
      helicase family is represented by a single homologue in higher eukaryotes. To
      analyze the function of PIF1 homologues in mammals, we cloned the full length
      human PIF (hPIF) cDNA. Comparison of hPIF with its S. cerevisiae homologues
      showed that human PIF is equally similar to Pif1p and Rrm3p. Human PIF was
      expressed at low levels in a variety of tissues and immunofluorescence analysis
      showed that ectopic hPIF was localized to nuclear foci. hPIF was expressed in
      late S/G2 phase of the cell cycle and this cell cycle regulated abundance was
      conferred by both cell cycle regulated mRNA accumulation and ubiquitin-mediated
      degradation. Furthermore, hPIF is likely a target of the anaphase promoting
      complex/cyclosome as its abundance was decreased when an activator of the APC/C
      was overexpressed. Finally, antibodies against hPIF immunoprecipitated telomerase
      activity from human cell lines, and we have observed a physical interaction
      between hPIF and the catalytic subunit of telomerase, hTERT. Our data suggest
      that human PIF, like S. cerevisiae Pif1p, plays a role in telomerase regulation.

PMID- 17172856
TI  - Notch and minichromosome maintenance (MCM) proteins: integration of two ancestral
      pathways in cell cycle control.
AB  - Notch transmembrane receptors govern a highly evolutionarily conserved
      intercellular signaling mechanism activated by the engagement of Notch receptors
      by their cognate ligands expressed on neighboring cells. The subsequently cleaved
      intracellular domain of Notch receptors translocates to the nucleus where it
      interacts with the transcriptional regulator CSL, thereby regulating expression
      of target genes. The Notch pathway controls cell fate by regulating
      proliferation, differentiation, and apoptosis. Mini-chromosome maintenance (MCM)
      proteins are components of the prereplicative complex (pre-RC) that are essential
      for DNA replication. It has recently been shown that activated Notch
      downregulates mini-chromosome-maintenance (MCM) proteins MCM2 and MCM6 by a CSL
      dependent mechanism. Here, we review the canonical pathway mediated by Notch
      receptors and discuss recent findings connecting the Notch pathway with the
      ancestral MCM complex during cell cycle progression.

PMID- 17172857
TI  - Degradation of the hypoxia-inducible factor 1alpha: where does it happen?
AB  - Adaptive responses to hypoxia are essential for the survival of all organisms.
      Under hypoxic conditions, transcription of a large group of genes relevant for
      oxygen homeostasis is induced by the hypoxia-inducible factor-1 (HIF-1). These
      genes encode proteins that enable the cells to adapt to limiting oxygen levels by
      increasing oxygen delivery through induction of angiogenesis or erythropoiesis
      and producing ATP under anaerobic conditions. The stability of HIF-1alpha protein
      is also target of O2 regulation. At normoxia HIF-1alpha is hydroxylated at
      specific proline residues by a recently identified family of prolyl hydroxylases.
      Hydroxylated HIF-1alpha is recognized by the Von Hippel-Lindau tumor suppressor
      gene product (pVHL) as an ubiquitylation substrate that leads to proteasomal
      dependent degradation of HIF-1alpha. We have recently demonstrated that the major
      subcellular compartment where degradation of HIF-1alpha occurs is dependent on
      the levels of proteasomal activity and on the localization of HIF-1alpha.
      Furthermore we have shown that the localization of HIF-1alpha degradation is a
      cell type-characteristic parameter. These observations indicate new levels of
      complexity in the regulation of HIF-1alpha degradation.

PMID- 17172858
TI  - Identification of new p63 targets in human keratinocytes.
AB  - p63 is a transcription factor involved in the development of ectodermal tissues,
      including limb, skin and, in general, multilayered epithelia. We identified both
      activated and repressed genes in human keratinocytes via gene expression
      profiling of p63-depleted cells and validated 21 new primary targets by RT-PCR
      and ChIP location analysis. The p63 isoforms differentially activate or repress
      selected promoters. ChIPs in primary keratinocytes indicate that p63 targets are
      generally shared with p53, but some are p63-specific. Several growth suppressors
      are among repressed genes. The newly identified genes belong to pathways of
      growth and differentiation and are regulated in HaCaT differentiation and in
      stratification of human skin.

PMID- 17172859
TI  - Molecular imaging of human embryonic stem cells: keeping an eye on
      differentiation, tumorigenicity and immunogenicity.
AB  - Human embryonic stem cells (hESCs) are capable of differentiation into every cell
      type of the human being. They are under extensive investigation for their
      regenerative potential in a variety of debilitating diseases. However, the field
      of hESC research is still in its infancy, as there are several critical issues
      that need to be resolved before clinical translation. Two major concerns are the
      ability of undifferentiated hESCs to form teratomas and the possibility of a
      provoked immune reaction after transplantation of hESCs into a new host.
      Therefore, it is imperative to develop noninvasive imaging modalities that allow
      for longitudinal, repetitive, and quantitative assessment of transplanted cell
      survival, proliferation, and migration in vivo. Reporter gene-based molecular
      imaging offers these characteristics and has great potential in the field of stem
      cell therapy. Moreover, it has recently been shown that reporter gene imaging can
      be combined with therapeutic strategies. Here, we provide an outline of the
      current status of hESC research and discuss the concerns of tumorigenicity and
      immunogenicity. Furthermore, we describe how molecular imaging can be utilized to
      follow and resolve these issues.

PMID- 17172860
TI  - Applications of fluorescence for detecting rare sequence rearrangements in vivo.
AB  - Homologous recombination (HR) is an important pathway for the accurate repair of
      potentially cytotoxic or mutagenic double strand breaks (DSBs), as well as double
      strand ends that arise due to replication fork breakdown. Thus, measuring HR
      events can provide information on conditions that induce DSB formation and
      replicative stress. To study HR events in vivo, we previously developed
      Fluorescent Yellow Direct Repeat (FYDR) mice in which a recombination event at an
      integrated transgene yields a fluorescent signal. Recently, we published an
      application of these mice demonstrating that fluorescent recombinant cells can be
      directly detected within intact pancreatic tissue. Here, we show that in situ
      imaging is a more sensitive method for detecting exposure-induced recombinant
      cells, yielding statistical significance with smaller cohorts. In addition, we
      show inter-mouse and gender-dependent variation in transgene expression, examine
      its impact on data interpretation, and discuss solutions to overcoming the
      effects of such variation. Finally, we also present data on enhanced yellow
      fluorescent protein (EYFP) expression, showing that several tissues, in addition
      to the pancreas, may be amenable for in situ detection of recombinant cells in
      the FYDR mice. The FYDR mice provide a unique tool for identifying genetic
      conditions and environmental exposures that induce genotoxic stress in a variety
      of tissues.

PMID- 17172862
TI  - Nucleotide excision repair disorders and the balance between cancer and aging.
AB  - Cancer incidence increases with age and is driven by accumulation of mutations in
      the DNA. In many so-called premature aging disorders, cancer appears earlier and
      at elevated rates. These diseases are predominantly caused by genome instability
      and present with symptoms, including cancer, resembling "segments" of aging and
      are thus often referred to as "segmental progerias". Two related segmental
      progerias, Cockayne syndrome (CS) and trichothiodystrophy (TTD), don't fit this
      pattern. Although caused by defects in genome maintenance via the nucleotide
      excision DNA repair (NER) pathway and displaying severe progeroid symptoms, CS
      and TTD patients appear to lack any cancer predisposition. More strikingly,
      genetic defects in the same NER pathway, and in some cases even within the same
      gene, XPD, can also give rise to disorders with greatly elevated cancer rates but
      without progeria (xeroderma pigmentosum). In this review, we will discuss the
      connection between genome maintenance, aging and cancer in light of a new mouse
      model of XPD disease.

PMID- 17172861
TI  - TGFbeta1-induced activation of ATM and p53 mediates apoptosis in a Smad7
      dependent manner.
AB  - ATM, a DNA-damage sensitive kinase and p53, are frequently inactivated in a
      variety of cancers as they together with gammaH2AX are critical guardians against
      DNA damage. Here, we report of a functional cross-talk between the cytokine
      TGFbeta and p53, leading to apoptosis of epithelial cells, involving Smad7, a
      TGFbeta target gene p38 MAP kinase, and ATM. Using ectopic expression of p53,
      siRNA for Smad7, p38alpha-/- deficient cells and specific inhibitors, we show
      that TGF-beta induces apoptosis via ATM and p53 in epithelial cells.
      Intriguingly, Smad7 act as a scaffold protein to promote functional interactions
      between p38, ATM and p53 upon TGFbeta treatment, facilitating their activation.
      Smad7 colocalizes with gammaH2AX in DNA damage foci and was required for proper
      cell cycle checkpoints to prevent genetic instability. Our data imply that Smad7
      plays a crucial role upstream of ATM and p53 to protect the genome from insults
      evoked by extracellular stress.

PMID- 17172863
TI  - Primitive, quiescent and difficult to kill: the role of non-proliferating stem
      cells in chronic myeloid leukemia.
AB  - Recent studies have identified primitive, malignant stem cells which have entered
      the G0-phase of the cell cycle to become 'quiescent' and which are present, in
      small numbers, in all chronic myeloid leukaemia (CML) patients. These cells have
      attracted intense scrutiny because they are proving exceptionally refractory to
      attempts to kill them, in vitro, using imatinib mesylate, the current first-line
      therapy for CML, or conventional chemotherapeutic agents, such as cytosine
      arabinoside. This insensitivity, or resistance, to drug treatment is ominous and
      has important implications for the clinical management of CML, particularly with
      regard to relapse following an imatinib-induced remission. In this review, we
      consider the known properties of this cell population, including recent evidence
      which suggests that transcription of BCR-ABL occurs at an exceptionally high
      level in these cells despite them having only a single copy of the oncogene. We
      also discuss possible alternative, Bcr-Abl-independent, mechanisms for the
      insensitivity of these cells to agents which promote apoptosis, including the
      putative role of transporter proteins in causing abnormal drug influx or efflux.

PMID- 17172864
TI  - A new role for microRNA pathways: modulation of degeneration induced by
      pathogenic human disease proteins.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of
      target transcript mRNAs. Many miRNAs have been defined, however their roles and
      the processes influenced by miRNA pathways are still being elucidated. A role for
      miRNAs in development and cancer has been described. We recently isolated the
      miRNA bantam (ban) in a genetic screen for modulators of pathogenicity of a human
      neurodegenerative disease model in Drosophila. These studies showed that
      upregulation of ban mitigates degeneration induced by the pathogenic
      polyglutamine (polyQ) protein Ataxin-3, which is mutated in the human
      polyglutamine disease spinocerebellar ataxia type 3 (SCA3). To address the
      broader role for miRNAs in neuroprotection, we also showed that loss of all
      miRNAs, by dicer mutation, dramatically enhances pathogenic polyQ protein
      toxicity in flies and in human HeLa cells. These studies suggest that miRNAs may
      be important for neuronal survival in the context of human neurodegenerative
      disease. These studies provide the foundation to define the miRNAs involved in
      neurodegenerative disease, and the biological pathways affected.

PMID- 17172865
TI  - Dynamic regulation of effector protein binding to histone modifications: the
      biology of HP1 switching.
AB  - Post-translational modifications of histone proteins, the basic building blocks
      around which eukaryotic DNA is organized, are crucially involved in the
      regulation of genome activity as they control chromatin structure and dynamics.
      The recruitment of specific binding proteins that recognize and interact with
      particular histone modifications is thought to constitute a fundamental mechanism
      by which histone marks mediate biological function. For instance, tri-methylation
      of histone H3 lysine 9 (H3K9me3) is important for recruiting heterochromatin
      protein 1 (HP1) to discrete regions of the genome, thereby regulating gene
      expression, chromatin packaging, and heterochromatin formation. Until now, little
      was known about the regulation of effector-histone mark interactions, and in
      particular, of the binding of HP1 to H3K9me3. Recently, we and others presented
      evidence that a "binary methylation-phosphorylation switch" mechanism controls
      the dynamic release of HP1 from H3K9me3 during the cell cycle: phosphorylation of
      histone H3 serine 10 (H3S10ph) occurs at the onset of mitosis, interferes with
      HP1-H3K9me3 interaction, and therefore, ejects HP1 from its binding site. Here,
      we discuss the biological function of HP1 release from chromatin during mitosis,
      consider implications why the cell controls HP1 binding by such a methylation
      phosphorylation switching mechanism, and reflect on other cellular pathways where
      binary switching of HP1 might occur.

PMID- 17172866
TI  - p21(Waf1/Cip1) deficiency stimulates centriole overduplication.
AB  - Inactivation of the cyclin-dependent kinase (CDK) inhibitor p21(Waf1/Cip1)
      (CDKN1; hereafter p21) has previously been implicated in the induction of
      numerical centrosome alterations. It is unclear, however, whether p21 deficiency
      deregulates the centrosome duplication cycle itself or causes an accumulation of
      centrosomes due to cell division failure and/or polyploidization. Using a novel
      marker for maternal centrioles, Cep170, we show here that knock-down of p21
      protein expression in murine myeloblasts can stimulate excessive centriole
      numbers in the presence of only one mature centriole. These results indicate that
      p21 deficiency can trigger a bona fide overduplication of centrioles and that
      aberrant centrosome numbers cannot solely be explained by polyploidization as
      suggested by previous studies. Our findings underscore that impaired p21
      expression may function as a driving force for chromosomal instability and
      highlight the importance of markers for maternal centrioles such as Cep170 to
      elucidate the pathogenesis of numerical centriole aberrations in tumor cells.

PMID- 17172867
TI  - Human Cdc14A reverses CDK1 phosphorylation of Cdc25A on serines 115 and 320.
AB  - Human Cdc14A is an evolutionary conserved dual-specificity protein phosphatase
      that reverses the modifications effected by cyclin-dependent kinases and plays an
      important role in centrosome duplication and mitotic regulation. Few substrates
      of Cdc14A have been identified, some of them with homologues in yeast that, in
      turn, are substrates of the Saccharomyces cerevisiae Cdc14 homologue, a protein
      phosphatase essential for yeast cell viability owing its role in mitotic exit
      regulation. Identification of the physiological substrates of human Cdc14A is an
      immediate goal in order to elucidate which cellular processes it regulates. Here,
      we show that human Cdc14A can dephosphorylate Cdc25A in vitro. Specifically, the
      Cdk1/Cyclin-B1-dependent phosphate groups on Ser115 and Ser320 of Cdc25A were
      found to be removed by Cdc14A. Cdc25A is an important cell cycle-regulatory
      protein involved in several cell cycle transitions and checkpoint responses and
      whose function and own regulation depend on complex
      phosphorylation/dephosphorylation-mediated processes. Importantly, we also show
      that the upregulation of Cdc14A phosphatase affects Cdc25A protein levels in
      human cells. Our results suggest that Cdc14A may be involved in the cell cycle
      regulation of Cdc25A stability.

PMID- 17172868
TI  - Claspin: timing the cell cycle arrest when the genome is damaged.
AB  - DNA damage checkpoints maintain genomic integrity by delaying cell cycle
      progression in response to genotoxic stress and stalled replication forks. One
      central pathway in the checkpoint response is the ATR-Chk1 pathway, in which,
      upon DNA damage, ATR phosphorylates and activates the effector kinase Chk1. This
      process depends on the adaptor protein Claspin that bridges ATR and Chk1. Once
      the damage is repaired, this pathway must somehow be switched off to allow the
      cell to continue the cell division process, an event known as checkpoint
      recovery. Polo-like kinase 1 (Plk1) plays a central role during checkpoint
      recovery. Interestingly, the Xenopus homologue of Plk1, Plx1, is able to bind and
      phosphorylate Claspin, releasing it from DNA and thereby contributing to Chk1
      inactivation. Moreover, it was recently demonstrated that Claspin levels are
      controlled by proteasomal degradation, and this is regulated by Plk1.
      Importantly, Plk1-mediated proteosomal degradation of Claspin appears to be
      essential for check-point recovery. Here we review these recent findings and
      discuss the mechanisms of checkpoint regulation by Claspin.

PMID- 17172869
TI  - TIS11D is a candidate pro-apoptotic p53 target gene.
AB  - A number of target genes for the tumor suppressor, p53, have been identified,
      however, the mechanisms that contribute to p53-dependent apoptosis remain to be
      fully elucidated. In a comprehensive screen for p53 target genes by differential
      display, we have identified TIS11D as a p53-inducible gene. Induction of TIS11D
      mRNA was confirmed by Northern Blot in response to p53 expression. Inducible
      expression of TIS11D resulted in inhibition of cell proliferation and apoptosis.
      These data suggest TIS11D as a candidate p53 target gene that may be part of the
      network of genes responsible for p53-dependent apoptosis.

PMID- 17172870
TI  - Budding yeast DNA damage adaptation mutants exhibit defects in mitotic exit.
AB  - In the presence of double strand breaks, DNA damage checkpoint halts cell cycle
      progression. However, cells ultimately escape the checkpoint arrest and reenter
      cell cycle in the presence of irreparable DNA damage. cdc5-ad was identified as a
      mutant that fails to adapt to the cell cycle arrest induced by DNA damage
      checkpoint. In budding yeast, Cdc5 protein kinase is a component of both MEN and
      FEAR pathways that are required for mitotic exit. It remains unclear whether the
      adaptation defect of cdc5-ad mutant cells is related to the function of Cdc5 in
      mitotic exit. Here we present evidence indicating that cdc5-ad mutant cells
      exhibit defects in mitotic exit. cdc5-ad mutant cells are sensitive to high
      dosage of Amn1, a negative regulator of MEN. It also shows synthetic growth
      defects with mutants in MEN pathway. Moreover, mutants in FEAR pathway exhibit
      defects in DNA damage adaptation. Thus, we conclude that the compromised mitotic
      exit pathway contributes to DNA damage adaptation defects in cdc5-ad mutant
      cells.

PMID- 17172871
TI  - False moves for survival: error-prone DNA repair in adaptive immunity.
AB  - Genetic stability and flexibility are major determinants of organismic integrity
      and evolution, respectively. An intricate DNA repair network protects the genome
      from multiple environmental challenges, but complex specialized processes may
      also allow enhanced mutability in critical situations. The interdependence and
      interference of these two systems is best exemplified in the adaptive immune
      system. Here, the coordinated reprogramming of DNA processing pathways allows the
      adaptation of the antibody response to specific infections, but in parallel
      increases the risk of malignant transformation of the affected B cells. The
      respective decisions in DNA repair pathway choice have now been linked to damage
      bypass processes occurring at stalled replication forks. Future research in this
      area may shed light on fundamental questions of both immunology and genetics, and
      provide translational concepts for improved cancer prognosis and therapy.

PMID- 17172872
TI  - Polo-like kinase 1: target and regulator of transcriptional control.
AB  - Deregulated cell cycle control is a hallmark of cancer cells. Developmental or
      other mitogenic stimuli activate the proliferation of normal cells in response to
      the requirements of growing tissues. In contrast, cancer cells liberate from
      proliferative restrictions exerted by anti-proliferative signals arising from the
      stroma and by endogenous genetic programs that correlate to the terminal
      differentiation of cells. The study of cyclin-dependent kinases (Cdks) and polo
      like kinases (Plks) as evolutionary conserved regulators of the cell cycle has
      contributed significantly to our current understanding of the mechanisms that
      underlie the proliferation of mammalian cells. Given the importance of Plk1 for
      mitotic progression the temporal expression of Plk1 is crucial and has to be
      tightly regulated. It is known that steady-state Plk1 mRNA and protein levels are
      coordinately regulated during cell cycle progression, being low during interphase
      but high in mitosis. This review will summarize the current knowledge on how cell
      cycle-dependent transcriptional regulation of the Plk1 gene is achieved. While
      binding sites for various transcriptional activators are dispersed throughout the
      entire Plk1 promoter region, the cell cycle-dependent regulation of the Plk1 gene
      expression seems to be regulated by G1-specific repression rather than by G2/M
      specific activation of the Plk1 transcriptional unit. The tumor suppressor gene
      p53 was identified as a key player in the precise restriction of Plk1 gene
      expression to the G2/M phase. The activity of p53 is in turn controlled by Plk1
      itself indicating the existence of an auto-regulatory mechanism involved in the
      cell cycle-dependent regulation of the Plk1 gene. Furthermore, transcription
      factors regulated by Plk1 will also be subject of discussion.

PMID- 17172873
TI  - GammaH2AX in cancer cells: a potential biomarker for cancer diagnostics,
      prediction and recurrence.
AB  - Current advances in cancer biology have identified major pathways involved in
      tumorigenesis. The association of DNA damage with premalignant stages of tumor
      progression, genome instability and further oncogenic transformation opens the
      possibility of using common DNA damage markers for early cancer detection,
      prediction, prognosis, therapeutics and possibly for cancer prevention. Perhaps
      the most sensitive DNA damage marker is gammaH2AX formation in the chromatin
      flanking the free DNA double-stranded ends in double-strand breaks (DSBs) and
      eroded telomeres, both present during oncogenic transformation. Our group and
      others found elevated endogenous levels of in various human cancer cell lines,
      premalignant lesions and solid tumors. These data suggest that increased DNA
      damage is a general characteristic of cancer development. GammaH2AX-based assay
      can be applied to human biopsies, aspirates and, possibly, to mononuclear cells
      of the peripheral blood. We propose that detection of gammaH2AX could benefit for
      the early cancer screening and to ascertain the efficiency of clinical treatment
      involving chemo- and radiotherapeutic protocols.

PMID- 17172874
TI  - Autologous bone marrow cell therapy and metabolic intervention in ischemia
      induced angiogenesis in the diabetic mouse hindlimb.
AB  - Peripheral arterial disease (PAD) is a major health problem especially when
      associated to diabetes. Administration of autologous bone marrow cells (BMC) is
      emerging as a novel intervention to induce therapeutic angiogenesis in
      experimental ischemic limb models and in patients with PAD. Since tissue ischemia
      and diabetes are associated with an overwhelming generation of oxygen radicals
      and detrimental effects due to formation of glycosylation end-products, metabolic
      intervention with antioxidants and L-arginine can confer beneficial effects
      beyond those achieved by BMC alone. The effects of cotreatment with intravenous
      BMCs and metabolic vascular protection (1.0% vitamin E, 0.05% vitamin C, and 6% L
      arginine) were examined in the ischemic hindlimb of diabetic and non diabetic
      mice. BMC therapy increased blood flow and capillary densities and Ki67
      proliferative marker, and decreased interstitial fibrosis. This effect was
      amplified by metabolic cotreatment, an intervention inducing vascular protection,
      at least in part, through the nitric oxide pathway, reduction of systemic
      oxidative stress, and macrophage activation.

PMID- 17172875
TI  - Eukaryotic domain of unknown function DUF738 belongs to Gcn5-related N
      acetyltransferase superfamily.

PMID- 17172876
TI  - Characterization of 14-3-3sigma dimerization determinants: requirement of
      homodimerization for inhibition of cell proliferation.
AB  - The seven highly conserved 14-3-3 proteins expressed in mammalian cells form a
      complex pattern of homo- and hetero-dimers, which is poorly characterized. Among
      the 14-3-3 proteins 14-3-3sigma is unique as it has tumor suppressive properties.
      Expression of 14-3-3sigma is induced by DNA damage in a p53-dependent manner and
      mediates a cell cycle arrest. Here we show that the 14-3-3sigma protein
      exclusively forms homodimers when it is ectopically expressed at high levels,
      whereas ectopic 14-3-3zeta formed heterodimers with the five other 14-3-3
      isoforms. The x-ray structure of 14-3-3sigma revealed five residues (Ser5, Glu20,
      Phe25, Q55, Glu80) as candidate determinants of dimerization specificity. Here we
      converted these amino-acids to residues present in 14-3-3zeta at the analogous
      positions. Thereby, Ser5, Glu20 and Glu80 were identified as key residues
      responsible for the selective homodimerization of 14-3-3sigma. Conversion of all
      five candidate residues was sufficient to switch the dimerization pattern of 14-3
      3sigma to a pattern which is very similar to that of 14-3-3zeta. In contrast to
      wildtype 14-3-3sigma this 14-3-3sigma variant and 14-3-3zeta were unable to
      mediate inhibition of cell proliferation. Therefore, homodimerization by 14-3
      3sigma is required for its unique functions among the seven mammalian 14-3-3
      proteins. As inactivation of 14-3-3sigma sensitizes to DNA-damaging drugs,
      substances designed to interfere with 14-3-3sigma homodimerization may be used to
      inactivate 14-3-3sigma function for cancer therapeutic purposes.

PMID- 17172877
TI  - K-turn motifs in spatial RNA coding.
AB  - Three-dimensional architectural motifs are increasingly recognized as
      determinants of RNA functionality. We submit that such motifs can encode spatial
      information. RNAs are targeted to subcellular localities in many eukaryotic cell
      types, and especially in neuronal and glial cells, RNAs can be transported over
      long distances to their final destination sites. Such RNAs contain cis-acting
      long-range targeting elements, and recent evidence suggests that kink-turn motifs
      within such elements may act as spatial codes to direct transport. Kink-turns are
      complex RNA motifs that feature double- and single-stranded components and
      introduce a signature three-dimensional structure into helical stems. We propose
      that the overall architectural design as well as the individual character--as
      specified by nucleotide identity and arrangement--of kink-turn motifs can serve
      as RNA targeting determinants.

PMID- 17172878
TI  - Drug-eluting stents: preventing restenosis.
AB  - The introduction of percutaneous transluminal coronary angioplasty has
      revolutionized the field of cardiology by providing patients with coronary artery
      disease immediate and effective therapy. Overshadowing the early success of
      angioplasty was the high rate of angiographic restenosis and recurrent symptoms
      at 6 months. The use of stents reduced the incidence of restenosis; however, the
      rise in the number of patients undergoing percutaneous interventions produced a
      new problem of restenosis occurring within the stent: in-stent restenosis (ISR).
      Mechanical approaches, including directional and rotational atherectomy and
      systemic pharmacotherapy, have failed to demonstrate a reduction in ISR in
      randomized clinical trials. Intravascular brachytherapy is currently the only
      approved therapy for ISR, although this treatment has numerous unresolved
      questions and is not effective in a large percent of patients. Drug-eluting
      stents have reduced the incidence of restenosis by providing localized therapy to
      the targeted lesion without systemic toxicity. The purpose of this review is to
      synthesize data from major clinical trials involving the 2 most successful agents
      used in the prevention of restenosis: sirolimus and paclitaxel. The cellular and
      molecular mechanisms of both ISR and restenosis postangioplasty derived from
      animal models will be introduced. Second, an overview of 3 alternate
      interventions that attempt to reduce the rates of restenosis is presented.
      Finally, the major randomized, controlled trials involving sirolimus and
      paclitaxel are described, and their clinical implications and use as a possible
      solution in the prevention of restenosis is discussed.

PMID- 17172879
TI  - Intravascular device infections: epidemiology, diagnosis, and management.
AB  - Intravascular devices such as pacemakers, implantable cardioverter-defibrillators
      (ICDs), left ventricular assist devices (LVADs), and prosthetic vascular grafts
      are life-saving therapies for patients with malignant arrhythmias, heart failure,
      and various vascular diseases. As indications for their use have increased, so
      has the prevalence of infectious complications associated with these devices. We
      present a review of the clinical literature on the epidemiology, diagnosis, and
      management of infectious complications of these intravascular devices. Most
      intravascular device infections are thought to result from skin flora
      contamination during implantation. Infection of the subcutaneous portion of the
      device can subsequently track to deeper intravascular tissues. Infection that
      involves the intravascular or intracardiac portion of these devices carries a
      high morbidity and mortality. Despite appropriate antibiotic therapy, cure of
      infection is frequently possible only with device removal. Well-designed placebo
      controlled, randomized studies evaluating antimicrobial therapy for treatment of
      intravascular device infections are lacking. In the absence of better
      information, authorities recommend antibiotics targeted toward cultured organisms
      for approximately 4 to 6 weeks and device removal.

PMID- 17172880
TI  - Acute pericarditis: diagnostic cues and common electrocardiographic
      manifestations.
AB  - Acute pericarditis (AP) is basically a clinical diagnosis. Although specific
      electrocardiographic (ECG) manifestations may indeed point to its diagnosis, sole
      reliance on such findings in isolation of the clinical setting, however, is often
      the common pitfall that could lead to a misguided diagnosis. We briefly review
      the anatomy of the pericardium and the pathophysiology of pericarditis to
      highlight common signs and symptoms as well as clinical findings that may assist
      in the diagnosis of AP. We also feature the characteristic evolution of its ECG
      manifestations and point out some of its typical and atypical features to help
      better differentiate AP from commonly confused conditions.

PMID- 17172882
TI  - Native American medicine and cardiovascular disease.
AB  - Native American medicine provides an approach to the treatment of cardiovascular
      disease that is unique and that can complement modern medicine treatments.
      Although specific practices among the various Native American tribes (Nations)
      can vary, there is a strong emphasis on the power of shamanism that can be
      supplemented by the use of herbal remedies, sweat lodges, and special ceremonies.
      Most of the practices are passed down by oral tradition, and there is specific
      training regarding the Native American healer. Native American medicine has
      strong testimonial experiences to suggest benefit in cardiac patients; however,
      critical scientific scrutiny is necessary to confirm the validity of the benefits
      shown to date.

PMID- 17172881
TI  - Blood is thicker than water: the management of hyperviscosity in adults with
      cyanotic heart disease.
AB  - Complications of chronic hypoxia, including erythrocytosis, hyperviscosity,
      abnormalities of hemostasis, cerebral abscesses, stroke, and endocarditis, are
      among the most common consequences of cyanotic heart disease in adults. The
      compensatory erythrocytosis of cyanotic heart disease can become pathologic by
      causing an increase in blood viscosity, thereby decreasing perfusion and
      resulting in decreased total oxygen delivery and increased risk of
      venoocclusive/hyperviscosity syndrome. Treatment of hyperviscosity secondary to
      erythrocytosis in cyanotic heart disease is controversial. Data is limited but
      suggest that phlebotomy has the potential to increase exercise capacity, reduce
      the symptoms of hyperviscosity, and reduce the potential risk of vasoocclusive
      disease in selected patients with polycythemia secondary to cyanotic heart
      disease. Unfortunately, repeated phlebotomy can quickly lead to iron deficiency,
      resulting in microcytic erythrocytes that induce higher viscosity than normocytic
      erythrocytes, which may increase the risk for venoocclusive events. There are
      limited data on the use of hydroxyurea to suppress erythrocytosis in this patient
      population. The authors conclude that until newer approaches to decreasing
      hematocrit without inducing iron deficiency are shown to be safe and efficacious,
      phlebotomy should only be used for the acute resolution of hyperviscosity
      symptoms. In addition, the use of hydroxyurea should be limited to patients with
      recurrent symptoms.

PMID- 17172883
TI  - P-wave dispersion and percutaneous mitral valvuloplasty.

PMID- 17172884
TI  - BiDil (isosorbide dinitrate and hydralazine): a new fixed-dose combination of two
      older medications for the treatment of heart failure in black patients.
AB  - BiDil is a new fixed-dose combination of 2 older medications, isosorbide
      dinitrate (ISDN) and hydralazine. ISDN is an organic nitrate that is
      biotransformed into nitric oxide, a potent vasodilator. Hydralazine is believed
      to have both vasodilatory properties specific to the arteries and antioxidant
      properties, which address both the biochemical alterations in the failing
      cardiovascular system as well as the issue of nitrate tolerance. A drug regimen
      combining an NO stimulator (ISDN) with an antioxidant (hydralazine) favorably
      influences the nitroso-redox balance. Retrospective analyses of previous heart
      failure (HF) clinical trials comparing the combination of ISDN and hydralazine
      with placebo and enalapril, respectively, demonstrated a benefit in the black
      population, setting the precedent for a race-based therapeutic study, the African
      American Heart Failure Trial (A-HeFT). A-HeFT examined the use of BiDil added to
      standard HF therapy in blacks with New York Heart Association functional class
      III and IV HF. BiDil demonstrated a 43% reduction in mortality when compared with
      placebo. As a result, current evidence-based treatment guidelines recommend that
      the addition of ISDN and hydralazine in black patients with moderate to severe HF
      optimized on standard therapy be considered. BiDil is currently indicated for the
      treatment of HF as an adjunct to standard therapy in black patients. The use of
      BiDil for black patients with mild disease or in nonblack patients with HF has
      not been studied. Future clinical trials involving an ethnically and clinically
      diverse population of patients would further define the role of combined ISDN and
      hydralazine in the treatment of HF.

PMID- 17172885
TI  - Corneal toxicity from topical ocular and systemic medications.
AB  - PURPOSE: To review what is known about the adverse effects on the cornea from
      various classes of medications. New data from previously unreported cases of drug
      related corneal toxicity are included. METHODS: Data are garnered from a Medline
      literature review and from case reports collected by the World Health
      Organization, the Food and Drug Administration, and the National Registry of Drug
      Induced Ocular Side Effects. RESULTS: Aminoglycosides, bisphosphonates,
      chemotherapeutic medications, cyclooxygenase-2 inhibitors, fluoroquinolones,
      glaucoma eye drops, topical iodine, nonsteroidal anti-inflammatory eye drops,
      preservatives in eye drops, retinoids, topical anesthetics, topical steroids, and
      some herbal medications can cause corneal toxicity in some patients. CONCLUSION:
      Ophthalmologists need to be aware of potential corneal toxicities that can arise
      from commonly prescribed medications.

PMID- 17172886
TI  - Comparison of implantable collamer lens (ICL) and laser-assisted in situ
      keratomileusis (LASIK) for low myopia.
AB  - PURPOSE: To compare the results of laser-assisted in situ keratomileusis (LASIK)
      and implantable collamer lenses (ICL) in the correction of myopia -4 to -7.88 D.
      METHODS: A total of 1678 LASIK eyes from the Davis Duehr Eye Center, Madison, WI,
      and 144 ICL eyes from the 14-site US FDA Clinical Trial for ICL for Myopia were
      compared. Both series were concurrently operated on with 4 to 7.88 D of
      preoperative spherical equivalent of the manifest refraction and were examined at
      1 day, 1 week, 1 month, and 6 months postoperatively. The mean baseline myopia
      was slightly higher in the ICL group (ICL: -6.4 +/- 1.1 D; LASIK: -5.6 +/- 1.1
      D). Best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity
      (UCVA), and refractions were collected prospectively in both series. RESULTS:
      BSCVA loss of at least 2 lines was significantly higher in the LASIK series in
      the early healing period (1 week: 6% vs. 0.7%; P = 0.008), whereas a BSCVA gain
      of at least 2 lines was statistically better with the ICL at 1 (5% vs. 0.9%, P =
      0.001) and 6 months (4% vs. 0.8%, P = 0.013). Proportion of cases seeing 20/15 or
      better uncorrected (21.6% vs. 7.8%, P < 0.001) and 20/20 or better (67% vs. 57%,
      P = 0.027) at 6 months postoperatively was better in the ICL group. The ICL was
      statistically more predictable (attempted vs. achieved) at 6 months; +/-0.50 D
      (79% ICL vs. 70% LASIK, P = 0.034) and +/-1.0 D (97% ICL vs. 88% LASIK, P <
      0.001). Stability was achieved (95% < or = 1.0 D) at the 1-week to 1-month
      interval for both groups (95% LASIK; 98% ICL). The stability of refraction (< or
      =0.5 D change) was significantly better in the ICL group than the LASIK group
      through 6 months. No serious complications occurred in either series.
      CONCLUSIONS: The ICL was safer and more effective than LASIK and seems to be a
      viable alternative to corneal refractive excimer surgery in the treatment of low
      myopia.

PMID- 17172887
TI  - Systemic tacrolimus in the treatment of severe atopic keratoconjunctivitis.
AB  - PURPOSE: Severe atopic keratoconjunctivitis (AKC) forms part of the spectrum of
      allergic eye disease and is often refractory to conventional topical treatment.
      Topical cyclosporin A and tacrolimus have been shown to reduce immunologic
      activation, symptoms, and signs of patients suffering from AKC, but there are no
      reports on safety and efficacy of systemic tacrolimus for this condition.
      METHODS: We report on a retrospective study of 3 patients with severe AKC, where
      the disease did not respond to conventional therapy, and they were therefore
      treated with low-dose systemic tacrolimus for at least 1 year as an adjunct to
      their existing treatment. RESULTS: There was a good clinical response in all
      patients to low-dose systemic tacrolimus, with a low incidence of side effects
      and no relapse of symptoms after discontinuation of treatment. CONCLUSION: Low
      dose systemic tacrolimus is a safe and effective treatment of some patients with
      severe AKC, which is refractory to conventional treatment. Such patients need
      careful monitoring for side effects, and the long-term benefits need to be
      assessed as part of a clinical trial.

PMID- 17172888
TI  - Long-term efficacy of phototherapeutic keratectomy on recurrent corneal erosion
      syndrome.
AB  - PURPOSE: To assess the long-term sequelae, principally time-to-first-recurrence,
      of phototherapeutic keratectomy (PTK) for the treatment of recurrent corneal
      erosion syndrome (RCES). METHODS: A retrospective case series was performed.
      Thirty-nine eyes in 33 patients with RCES required PTK and were treated using the
      VISX STAR Excimer Laser System. The data were analyzed with the Kaplan-Meier
      survival estimate. RESULTS: Patients were characterized by the cause of their
      RCES. More than 50% had epithelial corneal dystrophies, 31% were posttraumatic,
      and 15% were idiopathic. Overall, 25% of eyes had a recurrence by 3 months, and
      36% had a recurrence by 9 months. The mean follow-up time was 17.4 months (range,
      0.4-67.6 months). Of those who had a primary recurrence, 38% had a second and 15%
      had a third. Visual acuity was slightly decreased within 2 weeks after surgery,
      and 10% of patients developed transient haze. No serious adverse effects were
      reported. CONCLUSION: PTK is an important treatment of RCES refractory to other
      therapies. Long-term data suggest that most patients treated with PTK do not
      develop recurrences, and side effects from PTK are minimal.

PMID- 17172890
TI  - Correction factor in Orbscan II in the assessment of corneal pachymetry.
AB  - PURPOSE: Comparison of corneal pachymetry assessment with ultrasound and Orbscan
      II using acoustic factor and subtraction methods. METHODS: Ultrasound and Orbscan
      pachymetry for all patients with LASIK performed between July 2002 and May 2003
      were retrospectively analyzed. Comparison between the 2 preoperative measurements
      was analyzed. RESULTS: Using a custom acoustic factor of 0.93, there was no
      significant difference between the overall ultrasound and Orbscan pachymetry (P =
      0.696). However, there was underestimation in thick corneas and overestimation in
      thin corneas. Using the subtraction method as the correcting technique, the
      magnitude of over- and underestimation was reduced. CONCLUSION: The current
      correction method by means of acoustic factor may result in error in assessing
      extremes of corneal thickness. Alternative approaches such as the subtraction
      method can be considered to achieve more accurate results.

PMID- 17172889
TI  - Tear film normalization test: a new diagnostic test for dry eyes.
AB  - PURPOSE: To evaluate the normalization of the tear film (tear film normalization
      test [TNT]) as a diagnostic test for dry eye syndrome. METHODS: The uncorrected
      distance vision of 20 patients with dry eyes (40 eyes) and 20 normals (40 eyes)
      before and after instillation of carboxymethyl cellulose 0.5% (CMC; Refresh Plus;
      Allergan, Irvine, CA) was recorded. We used study early treatment diabetic
      retinopathy (ETDRS) vision charts to test vision in each eye. Tear film breakup
      time (TBUT), presence or absence of superficial punctate erosions (SPE), tear
      film meniscus height, meibomian gland function, and ocular surface disease index
      (OSDI) questionnaire scores were evaluated. RESULTS: CMC improved visual acuity
      in the dry eye group (P < 0.0001). Response operator's curve (ROC) analysis
      showed that vision improvement of 2 lines or more after tear normalization was
      associated with an 82.5% (95% CI: 66.6%-92.1%) sensitivity and 100% (95% CI:
      89.1%-100%) specificity for dry eye. There was a significant correlation between
      vision improvement and OSDI score in the dry eye group (P = 0.003). CONCLUSION:
      The TNT is a highly sensitive and specific test for dry eyes and is available in
      every eye care professional's office. The more symptomatic the dry eye, the
      greater the improvement.

PMID- 17172891
TI  - Prevalence of dry eye in Bangkok, Thailand.
AB  - PURPOSE: To estimate the prevalence of dry eye in the adult population of
      Bangkok, Thailand. METHODS: Five hundred fifty volunteers 40 years of age or more
      who presented to the Ramathibodi Hospital for annual eye examinations were
      enrolled. Interviewers administered a dry eye symptoms questionnaire. Slit-lamp
      examination and objective dry eye assessment consisting of tear film breakup time
      (TBUT), fluorescein corneal staining, Schirmer tests, and meibomian gland
      evaluation were performed. Outcome measures included frequency of symptoms and
      positive dry eye tests. RESULTS: Thirty-four percent reported significant
      symptoms, which were defined as having one or more symptoms often or all of the
      time (95% confidence interval, 28.1-40.6). Approximately one half had meibomian
      gland disease (MGD) or pingueculum/pterygium (46.2 and 53.8%, respectively).
      Individuals with significant symptoms tended to be women (83.4%, P = 0.024), had
      MGD (63.6%, P = 0.006), had current artificial tear use (33.2%, P = 0.024), and
      had positive TBUT (80.7%, P = 0.000) and fluorescein staining (16.6%, P = 0.013.)
      The presence of pingueculum/pterygium and MGD were significantly associated with
      positive dry eye tests. CONCLUSION: This is the first report of prevalence of dry
      eye inclusive of signs and symptoms in an elderly Thai population. The prevalence
      of disease diagnosed on the basis of symptoms and dry eye tests was approximately
      2 to 3 times higher than reported in whites. Women were more likely to report
      symptoms. Positive associations with dry eye tests were found in subjects with
      pingueculum/pterygium and MGD.

PMID- 17172892
TI  - Pterygium surgery: fibrin glue versus Vicryl sutures for conjunctival closure.
AB  - PURPOSE: To compare the short-term results of conjunctival closure in pterygium
      surgery using fibrin adhesive versus Vicryl sutures with respect to operative
      time, postoperative ocular signs and symptoms, and overall patient satisfaction.
      METHODS: A comparative prospective randomized clinical trial was performed in 65
      patients (65 eyes) with primary nasal pterygium. Surgery in all patients
      consisted of the bare sclera technique combined with intraoperative mitomycin C.
      Patients were randomized to undergo conjunctival closure with a fibrin tissue
      adhesive (Quixil; n = 39) or 8-0 Vicryl absorbable interrupted sutures (n = 26).
      Clinical assessment was performed on days 1, 3, 10, and 21 after surgery.
      Patients completed a questionnaire at each follow-up visit, grading pain,
      discomfort, and satisfaction with the procedure. The groups were compared for
      operative time, ocular signs and symptoms, and overall satisfaction. RESULTS:
      Average operative time was 16 minutes (range, 14-16 minutes) in the fibrin glue
      group and 20 minutes (range, 20-29 minutes) in the Vicryl suture group (P <
      0.05). Significantly less pain, photophobia, foreign body sensation, irritation,
      epiphora, itching, local hyperemia, conjunctival chemosis, and dry eye were noted
      in the subjects treated with glue than in controls (P < 0.05). There were no
      complications during the 3-week follow-up period in the glue-treated patients.
      One of the patients in the suture group had a medically treatable corneal delle.
      CONCLUSION: The use of fibrin glue in pterygium surgery significantly reduces
      operative time and patient symptoms, pain, and discomfort. A longer follow-up is
      needed to evaluate the influence of fibrin glue on rate of recurrence and long
      term complications.

PMID- 17172894
TI  - Effects of autologous serum eye drops on corneal wound healing after superficial
      keratectomy in rabbits.
AB  - PURPOSE: : To study the effects of topically applied autologous serum on the
      wound healing process of mechanically produced corneal ulcers. METHODS: : A
      superficial keratectomy was done in 1 eye from each of 28 rabbits, using a
      corneal trephine. Four groups of 7 rabbits were treated topically 4 times a day
      with nondiluted autologous serum; diluted autologous serum (20%); unpreserved
      pharmaceutical tear substitute; and physiologic saline. The saline-treated group
      served as a control. The healing of the ulcers was followed on a slit-lamp
      biomicroscope regarding its size, infiltration, and neovascularization on
      alternate days up to day 10 with and without fluorescein staining. RESULTS: :
      Autologous serum significantly accelerated the corneal wound healing process in
      both concentrations compared with either the unpreserved pharmaceutical tear
      substitute or physiologic saline solutions, but the process was faster with the
      nondiluted concentration. CONCLUSION: : Autologous serum eye drops could be used
      as a corneal wound healing adjuvant in mechanical corneal ulcers. To accelerate
      the wound healing process, the blood-derived factors were brought externally to
      the avascular cornea through autologous serum eye drops. The importance of the
      vascular supply on the wound healing process of vascular tissues is well known,
      and this study considers the benefit of blood-derived factors on the healing
      process of cornea.

PMID- 17172893
TI  - Long-term follow-up of the corneal endothelium after artisan lens implantation
      for unilateral traumatic and unilateral congenital cataract in children: two case
      series.
AB  - PURPOSE: To retrospectively estimate the long-term corneal endothelial cell loss
      in children after perforating corneal trauma and implantation of an iris-fixated
      anterior-chamber intraocular lens (IOL), either the Artisan aphakia lens or the
      Artificial Iris Implant, and to compare this corneal endothelial cell loss to
      that in children who received an Artisan aphakia lens to correct aphakia after
      cataract extraction for unilateral congenital cataract. METHODS: A retrospective
      study was performed, evaluating the charts and endothelial photographs of 6
      patients with unilateral traumatic cataract, with a mean age at IOL implantation
      of 9.5 years (range: 5.8-12.8 years) and a mean follow-up after IOL implantation
      of 10.5 years (range: 8.0-14.7 years), and of 3 children who were operated on for
      unilateral congenital cataract at a mean age of 2.7 years and who received an
      Artisan aphakia IOL, with a mean follow-up after IOL implantation of 9.5 years
      (range: 4.7-14.5 years). Parameters that were studied were central endothelial
      cell density (CECD) in both the operated and the normal eye at the last follow-up
      visit, percentage of cell loss in the operated eye compared with the normal eye,
      and length and location of the corneal scar in the injured eye. RESULTS: : In the
      traumatic cataract group, CECD was, on average, 41% (range: 22%-58%) lower in the
      operated eye (1.647 +/- 322 [SD] cells/mm) than the normal eye (2.799 +/- 133
      cells/mm). A significant negative linear correlation was found between the length
      of the corneal perforation scar and CECD. In the congenital cataract group, no
      statistical difference in CECD was found between the operated (3.323 +/- 410
      cells/mm) and the unoperated (3.165 +/- 205 cells/mm) eye. CONCLUSION:
      Endothelial cell loss 10.5 years after iris-fixated IOL implantation for
      traumatic cataract was substantial and related to the length of the corneal scar
      of the original trauma. In children operated on for congenital cataract, no
      difference was found in CECD in the operated and unoperated eyes 9.5 years after
      Artisan aphakia IOL implantation.

PMID- 17172895
TI  - Iontophoretic treatment of experimental pseudomonas keratitis in rabbit eyes
      using gentamicin-loaded hydrogels.
AB  - PURPOSE: To evaluate the efficacy of iontophoresis using a hydrogel probe
      containing gentamicin for the treatment of Pseudomonas keratitis in the rabbit
      cornea. METHODS: Five groups (Groups 1-5) of 8 rabbits each were infected by
      injecting Pseudomonas aeruginosa into their corneas. Three dosings of corneal
      iontophoresis were performed, at intervals of 3.5 hours, using soft disposable
      gentamicin-loaded hydroxyethyl methacrylate hydrogel discs mounted on a portable
      iontophoretic device. Groups 1 and 2 were treated with corneal iontophoresis for
      60 seconds and a current of 0.5 and 0.2 mA. Groups 3 and 4 were treated with
      hydrogel loaded with 0.9% NaCl solution, using a current of 0.2 mA and mock
      iontophoresis. Group 5 was treated with eye drops of 1.4% gentamicin every hour
      for 8 hours. One and a half hours after the last treatment, the animals were
      killed, and the corneas were excised and cultured for P. aeruginosa count after
      24-hour incubation. RESULTS: After iontophoretic treatment of gentamicin with a
      current of 0.5 mA (Group 1), the logarithmic value of Pseudomonas colony-forming
      units (CFUs) was 2.96 +/- 0.45. After lower current iontophoretic treatment
      (Group 2), the logarithmic Pseudomonas count was 5.25 +/- 0.54 CFUs. At the
      control groups (Groups 3-5), the Pseudomonas counts were found to be much higher,
      7.62 +/- 0.28, 7.22 +/- 0.29, and 6.29 +/- 0.45 CFUs, respectively. CONCLUSION: A
      short iontophoretic treatment using gentamicin-loaded hydrogels has potential
      clinical value in treating corneal infections.

PMID- 17172896
TI  - L-arginine-threonine-arginine (RTR) tetramer peptide inhibits ulceration in the
      alkali-injured rabbit cornea.
AB  - PURPOSE: Proline-glycine-proline (PGP) peptides have been identified as
      inflammatory mediators initiating neutrophil invasion into alkali-injured cornea.
      The complementary peptide, arginine-threonine-arginine (RTR), has been shown to
      bind to the PGP sequence and impede neutrophil infiltration. A prior study showed
      that L-RTR tetramer and D-RTR tetramer, used alternately (14 times a day),
      resulted in significantly reduced incidences of corneal ulceration and severity.
      The purpose of this experiment is to determine the effectiveness of both
      tetramers, used separately, compared with control. METHODS: Rabbit corneas were
      exposed to 1 N NaOH for 35 seconds. Sixteen animals were randomly assigned to
      each of 3 groups: 1) phosphate-buffered saline (PBS), 2) 1.5 mM L-RTR, or 3) 800
      microM D-RTR. One drop of each was administered hourly (14 times a day) for 36
      days. Additional studies were done to assess neutrophil infiltration into corneas
      with and without RTR treatment. RESULTS: The severity of corneal ulceration in
      both RTR groups was statistically significantly different from the 21st day of
      the experiment to the end. As a result of ulcers healing in the L-RTR group,
      there was a statistically significant reduction in the number of ulcers beginning
      on day 22 versus control. Although there was healing in the D-RTR group, the
      incidence of ulcers was not significantly different from control or L-RTR.
      Morphometric analysis revealed decreased neutrophil (PMN) invasion with RTR
      treatment compared with PBS control. CONCLUSIONS: Binding of the PGP molecules by
      RTR tetramer seems to deprive the cornea of this neutrophilic chemotactic
      stimulus, leading to a reduction in the severity and incidence of corneal
      ulceration.

PMID- 17172897
TI  - Expression in human ocular surface tissues of the GalNAc-transferases that
      initiate mucin-type O-glycosylation.
AB  - PURPOSE: Mucins are highly glycosylated proteins that act as lubricants,
      protectants, and mediators of signal transduction. The UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase (ppGaNTase) family members initiate mucin-type O
      glycosylation. Because O-glycosylation provides mucins with the viscoelastic
      properties required for proper mucin function, ppGaNTase expression is vital to
      the maintenance of healthy epithelial surfaces including the ocular surface.
      Differences of expression of ppGaNTase isoforms might be factors influencing
      susceptibility to dry eye disease. Therefore, we determined the expression of the
      ppGaNTase isoforms in normal human ocular surface tissues and the conjunctival
      epithelium from patients with aqueous-deficient dry eye. METHODS: Expression of
      ppGaNTase isoforms was quantitated by real-time reverse transcriptase polymerase
      chain rection (RT-PCR). RESULTS: Conjunctiva and cornea expressed multiple
      ppGaNTase isoforms, with isoforms T12 and T4 being the most strongly expressed in
      conjunctiva and T12 and T3 in the cornea. In contrast, lacrimal gland expressed
      fewer isoforms and had lower total ppGaNTase expression. Brush cytology was found
      to be superior to impression cytology for harvesting conjunctival epithelium in
      terms of ease of use, safety, and reproducibility of results. Similar to whole
      conjunctiva, the strongest isoforms in conjunctival epithelial cells were T12 and
      T4, followed by T3, T1, T5, and T2. No significant differences of ppGaNTase
      expression were found between the conjunctival epithelium of dry eye and normal
      control groups. CONCLUSION: Human ocular surface tissues express multiple
      ppGaNTase isoforms, suggesting a requirement for glycosylating diverse mucin-type
      substrates. However, there is no evidence to date to suggest that differences of
      ppGaNTase expression levels might contribute to susceptibility to dry eye
      disease.

PMID- 17172898
TI  - Investigation of corneal effect of different types of artificial tears in a
      simulated dry eye condition using a novel porcine dry eye model (pDEM).
AB  - PURPOSE: To use a novel porcine dry eye model (pDEM) to study the effect of
      various artificial tears on corneal abrasion and epithelial cell death under
      severe "dry eye" conditions. METHODS: A 60-second lacrimation-blink interval,
      which simulates a severe dry eye condition, was set up with our novel pDEM. The
      corneal protective effect of lubricating the eye for 4 hours with Dulbecco
      phosphate-buffered saline (DPBS, as control; n = 20) and with 3 types of
      commercially available artificial tears (n = 17 for each) that contained
      different lubricating agents was studied. Effect was determined in terms of the
      change in fluorescein staining grade (on a 0-4 point scale with 0.5 increments)
      of the cornea and the number of dead cells (by trypan blue staining) on the
      corneal surface. RESULTS: Median increase in fluorescein grading (median) in
      corneas treated for 4 hours with artificial tears containing sodium hyaluronate
      or hydroxypropyl methylcellulose was significantly (P < 0.002) smaller than with
      artificial tears containing balanced saline with an unknown demulcent or the DPBS
      control. The numbers of dead epithelial cells in the central corneas lubricated
      with artificial tears containing sodium hyaluronate or hydroxypropyl
      methylcellulose (229 +/- 71 and 221 +/- 65 [SD], respectively) were also
      significantly (P < 0.005) smaller than those in the corneas of eyes lubricated
      with artificial tears containing balanced saline with an unknown demulcent or
      DPBS alone (328 +/- 106 and 341 +/- 113, respectively). CONCLUSION: Results show
      that artificial tears containing sodium hyaluronate or hydroxypropyl
      methylcellulose as lubricating agents give enhanced corneal protection against
      desiccation and show the use of this novel pDEM model in evaluating corneal
      protection from desiccation.

PMID- 17172899
TI  - In vivo femtosecond laser-assisted posterior lamellar keratoplasty in rabbits.
AB  - PURPOSE: To develop a rabbit model for femtosecond laser-assisted posterior
      lamellar keratoplasty. METHODS: The femtosecond laser was used to make the
      posterior corneal lamellar interface and trephine (side) cut in 12 eyes of 11
      rabbits. Laser parameters were energy 6.0 to 8.7 (lamellar cut) and 6.0 to 8.8
      microJ (trephination cut), spot size 2.4 microm, firing rate 15 kHz, and
      trephination diameter 6.0 to 7.0 mm. In all eyes, the posterior corneal disc was
      removed from the eye after laser treatment through a blade incision in the
      peripheral cornea. The same excised corneal disc was repositioned into the
      posterior stromal bed to simulate posterior lamellar transplantation. Four eyes
      of 3 rabbits were enucleated immediately after surgery, and 8 eyes of 8 rabbits
      were enucleated after a mean follow-up of 17.9 +/- 6.5 weeks. The corneal cut
      surfaces were examined by light microscopy and scanning electron microscopy.
      RESULTS: The femtosecond laser was successful in producing posterior lamellar and
      trephination cuts in rabbit eyes. The thickness of the posterior corneal discs
      was 204.3 +/- 21 microm (56.9% of central corneal thickness), and postoperative
      keratometry was 49.1 +/- 5.8 D. Clinical appearance consistent with corneal
      ectasia was noted in 3 eyes. CONCLUSION: The femtosecond laser can make
      nonmechanical cuts for posterior lamellar keratoplasty with relative ease and
      reliability in rabbit eyes. A minimum residual anterior corneal thickness may
      need to be maintained to prevent ectasia.

PMID- 17172900
TI  - Growth and survival of Fusarium solani-F. oxysporum complex on stressed
      multipurpose contact lens care solution films on plastic surfaces in situ and in
      vitro.
AB  - PURPOSE: To analyze factors implicating the association of ReNu with MoistureLoc
      (ReNu ML) multipurpose contact lens solution (MPS) with the increased incidence
      of Fusarium keratitis. METHODS: Used contact lens cases with and without contact
      lenses and MPS containers were collected from patients with confirmed or possible
      Fusarium keratitis. Direct microscopy including transparent adhesive tape
      preparations and swab cultures were used to determine fungal colonization.
      Survival and growth of selected isolates of Fusarium spp. in drying MPS on
      plastic surfaces were determined by microscopy and recoverable colony counts on
      enriched agar. RESULTS: Discrete regions of fungal colonization, including
      occasional microcycle conidiation and chlamydospore formation, were observed on
      the surfaces of contact lens cases and, less often, on solution containers that
      had been used by patients with Fusarium keratitis associated with the use of ReNu
      ML. Isolates provisionally grouped with the F. solani-F. oxysporum complex were
      inhibited by fresh MPS in original solution containers and contact lens cases,
      but survived in stressed (drying) films of MPS, particularly ReNu ML. These in
      vitro test results were similar to the direct in situ observations of the
      materials from patients. CONCLUSIONS: Selective, rapid growth and survival of
      cells of the F. solani-F. oxysporum complex on plastic surfaces, particularly of
      contact lens cases with stressed ReNu ML films, may explain, in part, the recent
      Fusarium keratitis outbreak.

PMID- 17172901
TI  - Modified automated lamellar therapeutic keratoplasty for keratoconus: a new
      technique.
AB  - PURPOSE: To describe a modified automated lamellar therapeutic keratoplasty
      (ALTK) technique for the treatment of keratoconus. METHODS: The ALTK procedure
      was modified to include the use of a Hanna trephine system to control donor and
      recipient diameters and was performed in 2 stages. The recipient corneal lamellar
      bed was first prepared by creating a laser in situ keratomileusis (LASIK) flap at
      a preset depth that was left to heal over. The second stage involved the use of a
      Hanna trephination system to perform central trephination within the lamellar
      flap and transplantation of a donor lamellar graft that was fashioned to
      precisely match the recipient corneal bed, again using the Hanna donor punch to
      create a central trephination within the lamellar button obtained with the ALTK
      unit. RESULTS: The modified ALTK procedure effectively treated a patient with
      moderate keratoconus with a best-corrected visual acuity of 20/80, despite rigid
      gas-permeable contact lenses. Postoperatively, there was a significant reduction
      in the irregular astigmatism, and visual acuity improved to 20/25. There were no
      complications, and the ALTK interface remained clear throughout the 20-month
      follow-up period. CONCLUSIONS: ALTK combined with Hanna trephination enables
      precise control of both depth and diameter of lamellar dissection during surgery,
      removes the need for any form of manual dissection, and may therefore improve
      optical and visual outcomes in lamellar keratoplasty.

PMID- 17172902
TI  - Short-term mitomycin C followed by long-term interferon alpha2beta for
      conjunctiva-cornea intraepithelial neoplasia.
AB  - PURPOSE: To report a case of extensive conjunctiva-cornea intraepithelial
      neoplasia (CIN) treated topically with mitomycin C (MMC) and interferon (INF)
      alpha2beta without surgical resection. METHODS: Case report. RESULTS: : An 82
      year-old woman showed an extensive gelatinous red mass in the bulbar conjunctiva
      with invasion into the caruncle, inferior fornix, and tarsal conjunctiva and
      extending for 270 degrees of the corneal surface. A diagnosis of CIN was made by
      surgical biopsy. Surgical excision with safety margins carried the risk of limbal
      stem cell depletion. A conservative treatment strategy was used with 2 cycles of
      topical MMC (0.02%), followed by INF-alpha2beta eye drops at a dose of 1 million
      IU/mL, 4 times a day until tumor disappearance. Total resolution was noted after
      75 days of treatment with INF, with no clinical evidence of limbal stem cell
      deficiency. After 1 year of monitoring, no signs of CIN recurrences were
      observed. CONCLUSION: MMC (0.02%), followed by INF-alpha2beta (1 million IU/mL) 4
      times a day, is an effective treatment against highly extensive CIN, in cases
      where surgical resection with safety margins is unfeasible.

PMID- 17172903
TI  - Corneal perforation secondary to UV radiation from a tanning lamp.
AB  - PURPOSE: To report the case of a patient with keratoconus who developed a corneal
      perforation secondary to UV radiation from a tanning lamp. We believe this to be
      the first case of a corneal perforation secondary to UV radiation. METHODS: The
      presentation and management of the patient and the pathophysiology of UV
      keratitis are discussed. RESULTS: Our patient developed a full-thickness corneal
      perforation after 30 minutes of tanning lamp exposure without eye protection. The
      cornea was temporized with cyanoacrylate tissue adhesive until penetrating
      keratoplasty could be performed. CONCLUSION: With an increased understanding of
      the pathophysiology of UV damage, treatment should be aimed at modulating the
      disease to reduce the likelihood of a poor outcome.

PMID- 17172904
TI  - Detection of Streptococcus species by polymerase chain reaction in infectious
      crystalline keratopathy.
AB  - PURPOSE: Investigation of a positive polymerase chain reaction (PCR) for
      Streptococcus species from an excised cornea of a patient with infectious
      crystalline keratopathy. METHODS: Samples microdissected from corneal
      intrastromal aggregates present in infectious crystalline keratopathy were
      subjected to PCR for 3 primer pairs respectively specific for Streptococcus,
      Staphylococcus, and several kinds of fungi. RESULTS: The PCR detected DNA from
      Streptococcus but not from Staphylococcus or fungi. Direct sequencing of the PCR
      products showed that the PCR products had the highest identity (99.8%) with
      Streptococcus mitis and Streptococcus gordoni, indicating that these species were
      the most probable causes of infectious crystalline keratopathy in this patient.
      CONCLUSION: Our findings suggest that PCR provides a good adjunct technique in
      the diagnosis of corneal infection.

PMID- 17172905
TI  - Scytalidium keratitis: case report in a human eye.
AB  - PURPOSE: To describe the presentation and treatment of a case of an atypical
      reticular corneal infiltrate with surrounding immune-like ring in a young woman
      caused by Scytalidium fungal species. METHODS: Interventional case report
      describing the clinical appearance, course, and treatment of Scytalidium
      keratitis. RESULTS: A 21-year-old female equestrian with a history of soft
      contact lens wear was noted to have persistent keratitis and photophobia of the
      right eye after an injury with a volleyball. Although initially culture negative
      and responsive to topical steroids, the keratitis persisted, and repeat corneal
      scrapings and cultures revealed Scytalidium species. Treatment with topical
      amphotericin B 0.15% and oral fluconazole 200 mg twice daily eradicated the
      infection, and the patient had a final best-corrected visual acuity of 20/20.
      CONCLUSION: Scytalidium species fungal organisms can cause an indolent keratitis.
      Intensive oral and topical antifungal therapy was successful in eradicating the
      infection.

PMID- 17172906
TI  - Infectious keratitis caused by Stenotrophomonas maltophilia and yeast
      simultaneously.
AB  - PURPOSE: To report a case of coinfection of the human cornea by Stenotrophomonas
      maltophilia and yeast. METHODS: A 59-year-old woman presented with a corneal
      ulcer. The corneal lesion worsened suddenly after initial improvement with
      empirical antibiotic treatment. A culture revealed S. maltophilia. The keratitis
      rapidly progressed despite treatment with sensitivity-proven antibiotic agents.
      Eventually, the patient underwent therapeutic penetrating keratoplasty. RESULTS:
      Pathology of the cornea showed yeast forms and pseudohyphae scattered over the
      cornea. After surgery, the inflammation was controlled without any signs of
      recurrent infection. CONCLUSION: Coinfection of the cornea by S. maltophilia and
      yeast may occur in a susceptible cornea and may not be controlled by standard
      medical treatment.

PMID- 17172907
TI  - IgG-kappa immunoglobulin deposits involving the predescemetic region in a patient
      with multiple myeloma.
AB  - PURPOSE: To report the clinico-pathologic features of corneal deposits in a
      patient with multiple myeloma with surgical intervention and follow-up. DESIGN:
      Interventional case report. METHODS: We reviewed the patient's chart and the
      relevant literature on immunoglobulin corneal deposits and its prognosis.
      RESULTS: A 52-year-old man with a history of multiple myeloma underwent
      penetrating keratoplasty sequentially for decreased vision in both eyes secondary
      to abnormal corneal deposits. Pathologic examination of the keratectomy
      specimens, including immunohistochemistry and transmission electron microscopy,
      revealed IgG-kappa immunoglobulin deposits in the predescemetic region in both
      corneas. After keratoplasty, he regained excellent vision in both eyes, which was
      maintained at the end of 18 months of follow-up in both eyes despite early signs
      of recurrence in the right eye. His systemic condition was well controlled during
      the period of follow-up. CONCLUSION: Corneal deposits in multiple myeloma are
      well described in the literature, but there are few reports regarding the
      prognosis and visual function after penetrating keratoplasty. Our report shows
      that when the systemic condition is well controlled, penetrating keratoplasty has
      an excellent prognosis in these patients.

PMID- 17172908
TI  - Successful treatment of Paecilomyces lilacinus keratitis in a patient with a
      history of herpes simplex virus keratitis.
AB  - PURPOSE: To report a case of Paecilomyces lilacinus keratitis, initially
      misdiagnosed as Penicillium sp., in a patient with a long-standing history of
      herpes simplex virus (HSV) keratitis. METHODS: A retrospective case report.
      RESULTS: A 62-year-old man developed P. lilacinus keratitis. He was treated with
      topical steroids for immune stromal keratitis secondary to HSV before developing
      the fungal keratitis. Initial corneal cultures were positive for Penicillium sp.,
      but subsequent cultures identified P. lilacinus to be the causative organism. The
      patient later developed an anterior chamber abscess. Three penetrating
      keratoplasties, as well as intravitreal injection of amphothericin B, topical
      miconazole, subconjunctival miconazole, and systemic fluconazole, were required
      to eradicate the infection. CONCLUSION: To our knowledge, this is a first report
      of P. lilacinus keratitis in a patient with a previous history of HSV keratitis.
      The causative organism was initially reported as Penicillium sp. on 2 occasions,
      before the correct diagnosis was made. Paecilomyces keratitis progressed to an
      anterior chamber abscess in this eye. Aggressive treatment, including a
      therapeutic penetrating keratoplasty, intravitreal amphothericin B injection,
      topical miconazole, and systemic fluconazole can be successful in eradicating
      this extremely difficult-to-treat infection.

PMID- 17172909
TI  - Amphotericin B in the therapy of Candida glabrata endophthalmitis after
      penetrating keratoplasty.
AB  - PURPOSE: Candida glabrata is a rare cause of endophthalmitis after penetrating
      keratoplasty. Adequate therapy is still under discussion. With respect to severe
      complications and side effects of antifungal therapy, a substantial knowledge of
      sensitivity and resistance of the organism is necessary. METHODS: We report on a
      26-year-old man with a hyperacute onset of the infection only 10 hours after
      surgery. A combined therapy for fluconazole and steroids administered over 3
      months had shown no effect on intraocular infection. RESULTS: After topical and
      intracameral application of amphotericin B in combination with topical
      prednisolone 3 months after the onset of the endophthalmitis, the infection
      disappeared within 14 days, and the graft remained clear for 2 months. No toxic
      effects were noticed. CONCLUSION: In the case presented here, topical and
      intracameral application of amphotericin B was sufficient and safe in the therapy
      for C. glabrata endophthalmitis after penetrating keratoplasty. Although
      typically the intraocular infection is first noticed within the first 2 weeks, a
      hyperacute onset has to be considered.

PMID- 17172910
TI  - Gemella haemolysans infectious crystalline keratopathy.
AB  - PURPOSE: To report a case of infectious crystalline keratopathy caused by Gemella
      haemolysans. METHODS: Observational case report. A 65-year-old woman underwent
      penetrating keratoplasty for contact lens-related Acanthamoeba keratitis and
      developed a nonhealing epithelial defect. Despite continued prophylaxis with
      topical gatifloxacin, small superficial stromal opacities were noted and cultured
      6 months after penetrating keratoplasty. The opacities coalesced into a fine,
      crystalline keratopathy in the superficial stroma with persistent overlying
      epithelial defect. RESULTS: Culture results from corneal scraping showed more
      than 100 colonies of G. haemolysans. Topical vancomycin was instituted, with
      complete resolution of the crystalline keratopathy and epithelial defect over the
      next 2 months. CONCLUSIONS: G. haemolysans can be a causative organism of
      infectious crystalline keratopathy. This infection can arise in a
      postkeratoplasty patient despite prophylaxis with a fourth-generation
      fluoroquinolone.

PMID- 17172911
TI  - Ocular indigo dye injury.
AB  - PURPOSE: To describe the clinical course, management, and final outcome in a case
      of ocular injury caused by accidental fall of indigo dye in both eyes. METHODS:
      Review of patient's record and relevant literature. RESULTS: A 32-year-old man
      sustained ocular injury caused by inadvertent indigo dye in both eyes. He
      presented with bluish staining of the entire ocular surface, subtotal corneal
      epithelial breakdown in both eyes, and entry of dye into the anterior chamber in
      the left eye. This was treated as acute alkali burns with lubricants and
      steroids. Over a period of 3 to 4 months, the ocular surface staining resolved
      completely, and visual acuity improved remarkably. CONCLUSION: Although the
      clinical presentation was initially a cause for concern, the condition resolved
      completely with the same conservative management as applicable for other chemical
      injuries.

PMID- 17172912
TI  - Novel technique to control hypersecretion from a transplanted autologous
      submandibular salivary gland for keratoconjunctivitis sicca.
AB  - PURPOSE: To present a novel technique to control hypersecretion from a
      transplanted autologous submandibular gland (SMG) in a patient with
      keratoconjunctivitis sicca. METHODS: A 65-year-old man presented with corneal
      epithelial edema and suspicious ocular surface dysplasia secondary to
      hypersecretion from a transplanted autologous SMG. The location and function of
      the gland were evaluated perioperatively using technetium-99m-pertechnetate
      scintigraphy. The course of the duct was marked with a radiation probe,
      surgically exposed, and partially ligated with titanium clips. RESULTS: Marked
      reduction in salivary flow and resolution of corneal edema and ocular surface
      changes were noted. Conjunctival biopsy showed no evidence of malignancy.
      Symptoms were stable during a 1-year follow-up period. CONCLUSION: Partial
      ligation of the transplanted SMG duct may be a simple and reversible technique to
      control hypersecreting glands with secondary corneal edema and ocular surface
      changes.

PMID- 17172913
TI  - Camphor-related self-inflicted keratoconjunctivitis complicating delusions of
      parasitosis.
AB  - PURPOSE: To report a case of camphor-related self-inflicted keratoconjunctivitis
      secondary to delusions of parasitosis. METHODS: A 61-year-old man with delusions
      of parasitosis suffered from camphor-related self-inflicted ocular trauma that
      manifested with corneal epithelial defects and secondary anterior chamber
      reaction. Two episodes of exacerbation of the ocular conditions related to the
      use of camphor occurred. The left eye had secondary infection with
      Sternotrophomonas maltophilia and Staphylococcus aureus in the second episode of
      exacerbation. RESULTS: The right eye recovered well with the treatment of topical
      lubricants and corticosteroids and had best-corrected visual acuity (BCVA) of
      20/25. The infection of the left eye led to corneal perforation, necessitating
      penetrating keratoplasty; BCVA was hand motions because of a mature cataract.
      Olanzapine therapy for 1 month to decrease the delusions of parasitosis and 24
      hour watch to prevent the use of camphor led to the resolution of self-inflicted
      keratoconjunctivitis in the patient. CONCLUSIONS: Delusions of parasitosis may
      lead to vision-threatening self-inflicted ocular trauma. This may be the first
      case report of pure camphor-related self-inflicted toxic keratoconjunctivitis.

PMID- 17172914
TI  - Corneal ectasia after scleral buckling surgery.
AB  - PURPOSE: To describe a case of corneal ectasia with marked asymmetric progression
      attributable to encircling buckle surgery for retinal detachment. METHODS: Case
      report. RESULTS: A 72-year-old man developed clinical signs of pellucid marginal
      degeneration in 1 eye after placement of an encircling scleral buckle. The fellow
      eye showed normal slit-lamp examination, with topographic signs of forme-fruste
      pellucid marginal degeneration. CONCLUSION: Patients with forme-fruste pellucid
      marginal degeneration may show progression and clinical manifestations after
      encircling scleral buckle, probably by changes in ocular physiology and corneal
      biomechanics.

PMID- 17172915
TI  - Spontaneous wound dehiscence after removal of single continuous penetrating
      keratoplasty suture: conservative management.
AB  - PURPOSE: To describe a case of spontaneous wound dehiscence (WD) following
      removal of single continuous penetrating keratoplasty (PKP) suture, who was
      treated conservatively with a bandage contact lens. METHODS: A 36 year-old man
      who had penetrating keratoplasty for keratoconus 15 months earlier and removal of
      the single continues suture the previous week underwent ocular examination. He
      was treated with topical dexamethasone 0.3%, chloramphenicol 0.5% and
      cyclopentolate 1% 3 times a day and had a bandage contact lens (BCL) inserted.
      RESULTS: On presentation, he was complaining of reduced vision, tearing and pain
      following an attack of rhinitis-induced sneezing. His visual acuity (VA) in the
      affected eye was counting fingers, the anterior chamber was formed, the
      intraocular pressure (IOP) was low and there was a 2-clock-hour WD with a
      positive Seidel test but no iris incarceration. Two months later, his corrected
      VA was 6/5, his IOP was normal and the graft-host junction was good with no
      uplift. CONCLUSIONS: A 2-clock-hour WD after single continuous PKP suture removal
      may be conservatively treated with a BCL.

PMID- 17172917
TI  - Misuse and abuse of topically applied nonsteroidal anti-inflammatory drugs.

PMID- 17172916
TI  - Outcome of LASIK in fleck corneal dystrophy.
AB  - PURPOSE: To report the outcome of laser in situ keratomileusis (LASIK) in a
      patient with Fleck corneal dystrophy. METHODS: Case report and literature review.
      RESULTS: A 48-year-old Taiwanese man presented in November 2005, 6 years after
      bilateral myopic LASIK. He complained of loss of uncorrected distance visual
      acuity that was worse in the left eye. The patient did not report glare, halos,
      or other visual aberrations. Preoperative best spectacle-corrected visual acuity
      (BSCVA) was 20/25 OU, with a manifest refraction of -14 D OU. In November 2005,
      uncorrected visual acuity (UCVA) was 20/40 OD and 20/50 OS, and BSCVA was 20/25
      in each eye with a manifest refraction of -1.00 sphere OD and -1.75 -1.25 x 115
      OS. Slit-lamp examination was remarkable for several subtle, small, gray corneal
      opacities present throughout the corneal stroma. Confocal microscopy revealed
      refractile bodies within swollen keratocytes and normal surrounding stromal
      mileu. The clinical and confocal appearance was consistent with Fleck corneal
      dystrophy. CONCLUSION: In this patient with Fleck corneal dystrophy, corneal
      clarity and BSCVA were maintained 6 years after bilateral myopic LASIK,
      suggesting that LASIK does not stimulate visually significant exacerbation of
      Fleck corneal dystrophy.

PMID- 17172918
TI  - Three cases of corneal melting after instillation of a new nonsteroidal anti
      inflammatory drug.

PMID- 17172920
TI  - Corneal ulceration and perforation with ketorolac tromethamine.

PMID- 17172923
TI  - Association of RAGE gene polymorphisms with coronary artery disease in the Korean
      population.
AB  - BACKGROUND AND OBJECTIVES: AGEs (advanced glycation end products)-RAGE (receptor
      for advanced glycation end products) interaction in vessel wall may lead to
      inflammation, smooth muscle cell proliferation and extracellular matrix
      production, culminating in exaggerated intimal hyperplasia and restenosis. We
      focused on the putative association of five candidate RAGE gene polymorphisms on
      the risk of coronary artery disease in the Korean population. METHODS: A total of
      1555 male patients who underwent coronary angiography were enrolled in the study;
      805 patients (mean age: 53.18+/-9.74 years) had normal coronary artery and 750
      patients (mean age: 55.73+/-8.31 years) had significant coronary artery disease.
      Among the coronary artery disease patients, 269 had single-vessel disease
      (35.87%), 242 had two-vessel disease (32.27%) and 239 had three-vessel disease
      (31.87%). The genotypes of RAGE were determined by the methods of single base
      extension with amplifying primers and probes for TaqMan. Genotype analysis was
      performed on five single nucleotide polymorphisms of the RAGE gene, namely 
      443T>C, -388T>A, -257G>A, +557G>A and +1704G>T. Analysis for the association with
      coronary artery disease was performed. RESULTS: Analysis of four single
      nucleotide polymorphisms, except +557G>A (G82S), with regard to the association
      with coronary artery disease was not significant. Only the +557 gene allele (G/A)
      showed significant association with coronary artery disease (coronary artery
      disease vs. normal; G allele: 0.87 vs. 0.84, A allele: 0.13 vs. 0.16, P=0.0326).
      The +557G>A (G82S) showed strong tendency of association with coronary artery
      disease (coronary artery disease vs. normal; GG: 75.2 vs. 69.8%, GA: 23.2 vs.
      28.6%, AA: 1.6 vs. 1.6%, P=0.0524). The presence of AA or GA genotype, assuming
      codominant effect of the A allele, was independently associated with decreased
      risk of coronary artery disease when controlled for age, body mass index, smoking
      and diabetes mellitus [odds ratio=0.749 (95% confidence interval, 0.579-0.969),
      P=0.0280]. Subgroup analysis demonstrated the significant protective effect of AA
      or GA genotype in nondiabetic patients as well [odds ratio=0.741 (0.570-0.962),
      P=0.0244]. CONCLUSIONS: The results of this large population study demonstrate
      that the AA/GA genotypes of the RAGE +557G>A polymorphism are associated with a
      significantly decreased risk of significant coronary artery disease. Other
      polymorphisms of RAGE were not significantly associated with the risk of coronary
      artery disease in this study population.

PMID- 17172924
TI  - Endogenous testosterone and endothelial function in postmenopausal women.
AB  - OBJECTIVE: It is well known that coronary heart disease incidence increases in
      women after menopause. This phenomenon was related to reduced levels of female
      sex hormones. Estrogen decline, however, is not the only hormonal change during
      the postmenopausal period and estrogen administration did not protect women from
      cardiovascular disease. Therefore, it is justified to explore other hormonal
      changes. The role of androgens is still controversial. The aim of the present
      study was to investigate the relationship between endogenous sex hormones and
      endothelial function, measuring the brachial artery flow-mediated dilation.
      METHODS AND RESULTS: Sixty postmenopausal women were consecutively enrolled and
      underwent a clinical and biochemical examination. Brachial artery flow-mediated
      dilation was also evaluated by ultrasound. After correction for confounding
      variables, testosterone was positively correlated to flow-mediated dilation
      (beta=0.277, P=0.03). Indeed, women in the lowest testosterone tertile had a flow
      mediated dilation smaller than that in the highest tertile (P=0.02). CONCLUSIONS:
      This result could suggest that the development of cardiovascular disease after
      menopause is due not only to estrogen decline but also to androgen decline. More
      studies are needed to evaluate the role of androgen replacement therapy on
      postmenopausal women with low level of this hormone.

PMID- 17172925
TI  - Myocardial blood flow and oxygen consumption in patients with Friedreich's ataxia
      prior to the onset of cardiomyopathy.
AB  - OBJECTIVES: We tested the hypothesis, in patients with Friedreich's ataxia and no
      overt structural heart disease, that impairment of cardiac oxidative metabolism
      may be compensated for either by increased rest myocardial blood flow or more
      efficient oxygen consumption in performance of external work. BACKGROUND:
      Friedreich's ataxia is characterized by a mutant frataxin gene, which causes
      mitochondrial iron overload and impaired energy production. Further, it is
      frequently associated with cardiomyopathy. Studies using magnetic resonance
      spectroscopy, however, suggest impaired cardiac energetics even in the absence of
      structural heart disease. METHODS: Positron emission tomography measured rest
      myocardial blood flow (N-13-ammonia method) and myocardial oxygen consumption (11
      C-acetate, Kmono) in Friedreich's ataxia patients (n=8; 31+/-5 years, mean+/-SD,
      four women) and healthy controls (n=8; 30+/-7 years, five women) matched for
      stroke work index and age. Stroke work index and power were determined by
      electrocardiogram gated positron emission tomography N-13-ammonia using modified
      Simpson's rule to compute left ventricular volumes. RESULTS: Neither stroke work
      index nor rest myocardial blood flow differed significantly between the groups.
      Although myocardial oxygen consumption was lower in Friedreich's ataxia
      (P<0.001), Kmono/rest myocardial blood flow, an index of myocardial oxygen
      extraction, did not differ between the groups. Power/Kmono, an index of the
      efficiency of myocardial oxygen consumption, was greater in Friedreich's ataxia
      (P<0.04). Rest myocardial blood flow normalized to rate pressure product was
      lower in Friedreich's ataxia (P<0.05). CONCLUSIONS: Prior to the onset of
      cardiomyopathy, selected patients with Friedreich's ataxia may compensate for
      impaired cardiac energetics through more efficient oxygen consumption rather than
      increased rest myocardial blood flow. The data illustrate a more general
      mechanism pertaining to metabolic regulation of myocardial blood flow and
      myocardial oxygen consumption.

PMID- 17172926
TI  - An ultrasound-based comparative study on carotid plaques in HIV-positive patients
      vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory
      lesions?
AB  - BACKGROUND: We have previously described two cases of HIV-1-positive patients
      undergoing surgery for stenosis of the internal carotid arteries. Histology
      revealed an extensive inflammatory infiltration of the vascular wall and no
      evidence of atheromasic plaque. This unexpected pattern of carotid damage
      prompted us to perform a more accurate investigation of the characteristics of
      carotid plaques in a group of HIV-positive patients. The results were compared
      with those obtained from young patients affected by atherosclerosis of the epi
      aortic vessels and patients with arteritis. METHODS: The patients underwent
      ultrasonography of the epi-aortic vessels using one of the latest generation
      power color-Doppler with 7.5 MHz probes. RESULTS: The study population included
      61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10
      with arteritis). Compared with HIV-negative atherosclerotic patients, there were
      significantly higher proportions of HIV-positive patients with iso-hypoechogenic
      lesions (81.8 vs. 29%) that were homogeneous both in their parietal and
      endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a
      smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all
      differences). No statistically significant differences were seen between HIV
      positive and arteritis patients. CONCLUSION: Our study evidenced that the
      ultrasonographic structure of the epi-aortic lesions in HIV-positive patients
      substantially differ from those of the plaques in atherosclerotic patients,
      although they share similar characteristics with patients affected by arteritis.
      Further investigations are warranted to better define the structure and the
      mechanism of onset of these lesions.

PMID- 17172927
TI  - Association between Toll-like receptors and the extent and severity of coronary
      artery disease in patients with stable angina.
AB  - OBJECTIVES: Toll-like receptors mediate the innate immune response triggered by
      pathogen-associated molecular patterns, and atherosclerosis can be considered a
      state of chronic inflammation whereby immune system cells accumulate within the
      intima of the arterial wall. The goal of this study was to determine the relation
      of Toll-like receptors to the extent and severity of coronary artery disease.
      METHODS: Angiographic vessel score and Gensini score were used to evaluate the
      extent and severity of coronary atherosclerosis. Sixty-two consecutive patients
      with stable angina were grouped as follows: those with insignificant (<50%)
      coronary stenosis (group 1), and those with 1 (group 2), 2 (group 3), or 3-vessel
      disease (group 4). The expression of Toll-like receptor 1, 2, and 4 on
      circulating CD14+ monocytes was analyzed by flow-cytometry in all patients.
      RESULTS: Toll-like receptor 2 had a positive correlation with the vessel score
      and Gensini score (r=0.46, P<0.001; r=0.32, P<0.02, respectively). Toll-like
      receptor 4 also positively correlated with the vessel score and Gensini score
      (r=0.47, P<0.001; r=0.29, P<0.05, respectively). No significant correlation
      existed between the expression of Toll-like receptor 1 and the vessel score or
      Gensini score. Further, there was no significant correlation between high
      sensitivity C-reactive protein and the vessel score or Gensini score. CONCLUSION:
      These data suggest that Toll-like receptor 2 and 4 expression correlates with the
      extent and severity of coronary artery disease.

PMID- 17172928
TI  - Assessment of right ventricular infarction with contrast-enhanced magnetic
      resonance imaging.
AB  - OBJECTIVE: Evaluation of contrast-enhanced magnetic resonance imaging to assess
      right ventricular infarction in patients with acute inferior myocardial
      infarction. BACKGROUND: Contrast-enhanced magnetic resonance imaging has been
      used for assessing scar tissue after left ventricular infarction. The value of
      contrast-enhanced magnetic resonance imaging to assess right ventricular
      infarction is unknown and was evaluated. METHODS: Consecutive patients (n=18)
      with first acute inferior infarction were included. Resting electrocardiogram and
      right-sided electrocardiogram were acquired to assess right ventricular
      involvement. Resting cine magnetic resonance imaging was performed to evaluate
      right ventricular function and volumes, whereas the extent of right ventricular
      scar tissue was assessed by contrast-enhanced magnetic resonance imaging. Cine
      magnetic resonance imaging was repeated at 6-months follow-up to re-assess right
      ventricular function and volumes. RESULTS: Sensitivity and specificity of
      magnetic resonance imaging were 100 and 78%, respectively, to detect right
      ventricular infarction (using the right-sided electrocardiogram as the gold
      standard). At 6 months follow-up, patients with scar tissue on contrast-enhanced
      magnetic resonance imaging showed right ventricular dilatation. Moreover, the
      extent of right ventricular scar tissue was linearly related to the severity of
      right ventricular dilatation. CONCLUSIONS: Contrast-enhanced magnetic resonance
      imaging permits accurate assessment of right ventricular scar tissue. Patients
      with extensive right ventricular infarction demonstrate right ventricular
      dilatation at 6 months follow-up.

PMID- 17172929
TI  - Coronary blood flow in patients with cardiac syndrome X.
AB  - BACKGROUND: Epicardial coronary arteries are normal in patients with cardiac
      syndrome X. It is, however, unclear whether there is an abnormality at the level
      of microvascular circulation. In this study, our aim was to evaluate the
      epicardial coronary blood flow and myocardial perfusion in patients with cardiac
      syndrome X. METHODS: Two hundred and three patients (mean age 53+/-10 years, 85
      men) were included in the study. The diagnosis of cardiac syndrome X was made in
      patients who had a complaint of typical anginal chest pain and had ischemic
      findings on either myocardial perfusion scintigraphy or a treadmill exercise
      test, and whose coronary angiograms did not reveal any pathology. Fifty patients
      (mean age 54+/-11 years, 24 men) who had a complaint of typical anginal chest
      pain and had a normal myocardial perfusion test and normal coronary arteries were
      recruited as the control group. Epicardial coronary blood flow was evaluated with
      the thrombolysis in myocardial infarction frame count method and myocardial
      perfusion was evaluated with the myocardial blush grade method. A myocardial
      blush grade of < or =2 in any vessel was considered abnormal. RESULTS: Although
      the right coronary thrombolysis in myocardial infarction frame count was higher
      in patients with syndrome X (14.9+/-7.6 vs. 11.7+/-4.4 in controls; P=0.014),
      there were no statistically significant differences between the groups in terms
      of mean thrombolysis in myocardial infarction frame count in the coronary
      arteries. Abnormal myocardial blush grade was present in 85 patients (42.3%) with
      syndrome X, and in 17 patients (34.7%) in the control group (P>0.05). CONCLUSION:
      We found that the epicardial coronary blood flow, as assessed by thrombolysis in
      myocardial infarction frame count, and myocardial perfusion, as assessed by
      myocardial blush grade, were normal in patients with cardiac syndrome X.

PMID- 17172930
TI  - Expression of monocyte and lymphocyte adhesion molecules is increased in isolated
      coronary artery ectasia.
AB  - BACKGROUND: Coronary artery ectasia is defined as localized or diffuse dilation
      of the coronary arteries exceeding the 1.5-fold of normal adjacent segment.
      Scarce data are available about the role of inflammation in coronary artery
      ectasia. In the present study, we aimed to evaluate the expression of CD11b and
      CD45 adhesion molecules in peripheral blood granulocytes, monocytes and
      lymphocytes from the patients with coronary artery ectasia as possible indicators
      of inflammation. METHOD: The study consisted of 14 patients who had
      angiographically normal coronary arteries with coronary artery ectasia and 13 age
      and sex-matched controls without coronary artery ectasia. Cell surface adhesion
      molecules were detected by direct immunofluorescence evaluated by flow cytometry
      using monoclonal antibodies tagged with fluorescent markers. Venous blood samples
      were taken after coronary angiography. RESULTS: Mean fluorescence intensity of
      CD45 (33.8+/-3.1 vs. 13.0+/-0.7, P<0.001) and CD11b (39.1+/-13.5 vs. 19.5+/-1.32,
      P<0.001) on the monocyte surface of patients with coronary artery ectasia were
      higher than those of controls. Similarly in patients with coronary artery
      ectasia, the expression of CD11b (7.5+/-0.61 vs. 5.6+/-0.2, P=0.009) and CD45
      (47.5+/-3.6 vs. 36.2+/-2.5, P=0.02) on lymphocytes was also significantly higher
      than those of controls. CONCLUSION: Increased levels of cellular adhesion
      molecules in patients with coronary artery ectasia may be an indicator of
      endothelial activation and inflammation and are likely to be in the causal
      pathway leading to coronary artery ectasia.

PMID- 17172931
TI  - Effect of a hypoglycemic agent on ischemic preconditioning in patients with type
      2 diabetes and stable angina pectoris.
AB  - OBJECTIVE: Ischemic preconditioning is an increased tolerance to myocardial
      ischemia during the second of two consecutive exercise tests. ATP-sensitive K(+)
      channel blockers, such as glinides and sulfonylurea drugs, can induce loss of
      ischemic preconditioning. This study aimed to investigate the effects of
      repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K
      (+)channels, on the results of consecutive exercise tests in patients with
      diabetes and multivessel coronary artery disease. METHODS: Forty-two patients
      with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three
      vessel disease participated in this study. The patients underwent two consecutive
      treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg
      of oral repaglinide was given to the patients. One week later, two exercise tests
      were repeated consecutively (phase 2). RESULTS: All patients achieved 1.0-mm ST
      segment depression during the four exercise tests (T1, T2, T3, and T4). In phase
      2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The
      worsening of the time to onset of 1.0-mm ST-segment depression in phase 2
      demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even
      the postexercise electrocardiographic parameters (ST-segment depression
      morphology and magnitude and arrhythmias) were significantly different between
      the groups with and without pharmacologic ischemic preconditioning block
      (P=0.031). CONCLUSIONS: Repaglinide, an oral hypoglycemic agent with ATP
      sensitive K(+) channel-blocker activity, eliminated the myocardial ischemic
      preconditioning in patients with coronary disease and diabetes.

PMID- 17172932
TI  - Recombinant human-activated protein C inhibits cardiomyocyte apoptosis in a rat
      model of myocardial ischemia-reperfusion.
AB  - OBJECTIVES: Myocardial apoptosis is recognized as a major mechanism of cell death
      during ischemia-reperfusion. In this study, we assessed the hypothesis that
      activated protein C may have a cardioprotective effect via preventing apoptosis
      in a rat model of myocardial ischemia-reperfusion. METHODS: Thirty male Sprague
      Dawley rats were anesthetized, instrumented for hemodynamic measurements and
      ventilated mechanically. Twenty rats were subjected to 20 min of left anterior
      descending coronary artery occlusion and 2 h of reperfusion. They were randomly
      assigned to receive intravenous Ringer lactate (vehicle) or activated protein C
      (2 mg/kg/h) 10 min after occlusion and during reperfusion. The other 10 rats were
      sham-operated. At the end of the reperfusion period, serum samples were obtained
      for evaluation of creatine kinase, C-reactive protein and tumor necrosis factor
      alpha. Apoptosis was measured quantitatively by the terminal deoxynucleotide
      transferase-mediated dUTP nick-end labeling method. RESULTS: Serum creatine
      kinase, C-reactive protein and tumor necrosis factor-alpha values and percentage
      of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling- positive
      myocyte nuclei demonstrated negligible myocardial injury in sham-operated
      controls. During reperfusion, mean arterial pressures were significantly higher
      in activated protein C-treated rats than in the control group (68.2+/-10.3 vs.
      55.4+/-11.6 mmHg, P=0.01). Number of apoptotic cells was significantly reduced
      from 47.7 to 24.8% with activated protein C administration (P=0.008). No
      difference was seen between activated protein C-treated and untreated animals
      with respect to creatine kinase, C-reactive protein and tumor necrosis factor
      alpha levels. CONCLUSIONS: Treatment with activated protein C significantly
      improved hemodynamics after ischemia-reperfusion and reduced ischemia-reperfusion
      induced myocardial apoptosis in rats.

PMID- 17172933
TI  - Beta-blockers and statins are individually associated with reduced mortality in
      patients undergoing noncardiac, nonvascular surgery.
AB  - BACKGROUND: Patients undergoing noncardiac, nonvascular surgery are at risk for
      perioperative mortality owing to underlying (a)symptomatic coronary artery
      disease. We hypothesized that beta-blocker and statin use are associated with
      reduced perioperative mortality. METHODS: We performed a case-control study in 75
      581 patients who underwent 108 593 noncardiac, nonvascular surgery at the Erasmus
      Medical Center between 1991 and 2001. Cases were the 989 patients who died during
      hospital stay after surgery. From the remaining patients, 1879 matched controls
      (age, sex, calendar year and type of surgery) were selected. Information was then
      obtained regarding the use of beta-blockers and statins and the presence of
      cardiac risk factors. RESULTS: The median age of the study population was 63
      years; 61% were men. beta-blockers were less often used in cases than in controls
      (6.2 vs. 8.2%; P=0.05), as were statins (2.4 vs. 5.5%; P<0.001). After adjustment
      for the propensity of beta-blocker use and cardiovascular risk factors, beta
      blockers were associated with a 59% mortality reduction (odds ratio 0.41; 95%
      confidence interval 0.28-0.59). Statins were associated with a 60% mortality
      reduction (adjusted odds ratio 0.40; 95% confidence interval 0.24-0.68). A
      significant interaction between beta-blockers and statins was observed (P<0.001).
      In the presence of each other, statins and beta-blockers were not associated with
      reduced mortality (adjusted odds ratio 2.0 and 95% confidence interval 0.74-5.7
      and adjusted odds ratio 1.3 and 95% confidence interval 0.52-3.2). It should be,
      however, noted that only nine cases and 29 controls used both agents
      simultaneously. CONCLUSION: This case-control study provides evidence that beta
      blockers and statins are individually associated with a reduction of
      perioperative mortality in patients undergoing noncardiac, nonvascular surgery.

PMID- 17172934
TI  - Bibliography of current world literature.

PMID- 17172936
TI  - Uptake of BRCA1 rearrangement panel testing: in individuals previously tested for
      BRCA1/2 mutations.
AB  - PURPOSE: Individuals undergoing genetic testing for BRCA1/2 mutations are
      routinely counseled about the sensitivity and specificity of testing. In August
      2002, testing for 5 large genomic rearrangements in the BRCA1 gene that would not
      have been detected with full gene sequence analysis became commercially
      available. We present our data on uptake of the BRCA1 rearrangement panel testing
      in our clinical cancer genetics program. METHODS: Women who participated in our
      clinical genetic testing program and had previously received an uninformative
      negative or variant of uncertain significance result from BRCA1/2 full gene
      sequencing were invited to consider BRCA1 rearrangement panel testing. RESULTS:
      Overall, 18/72 individuals underwent BRCA1 rearrangement panel testing. No
      significant differences were found in the levels of BRCAPRO scores (P = 0.406),
      age at testing (P = 0.986), number of children (P = 0.35) or number of siblings
      (P = 0.4) between individuals who chose to pursue additional testing with the
      rearrangement panel and those who declined. Fisher's Exact Test analysis showed
      that there is a negative association between having breast or ovarian cancer and
      being inclined to undergo rearrangement panel testing (P = 0.013). CONCLUSION:
      Individuals who undergo genetic testing will not consistently pursue additional
      or enhanced genetic testing. Future research is needed to clearly elucidate the
      factors associated with uptake of additional genetic testing.

PMID- 17172937
TI  - Recall of disclosed apolipoprotein E genotype and lifetime risk estimate for
      Alzheimer's disease: the REVEAL Study.
AB  - PURPOSE: To determine whether individuals recall their apolipoprotein E genotype
      and numeric lifetime risk estimates after undergoing a risk assessment for
      Alzheimer's disease. METHODS: One-hundred and four participants underwent
      Alzheimer's disease risk assessment that included disclosure of apolipoprotein E
      genotype and a numeric lifetime risk estimate. RESULTS: At six weeks and one year
      post-disclosure, 59% and 48% of participants, respectively, recalled their
      lifetime risk estimate, and 69% and 63% recalled their apolipoprotein E genotype.
      Participants were more likely to remember their genotype than numeric lifetime
      risk estimate at one year (P < 0.05). Apolipoprotein E epsilon4-positive
      participants had better recall of their genotype at both time points (P < 0.05).
      Participants were more likely to recall whether they carried the "risk-enhancing
      form of apolipoprotein E" than their specific genotype (P < 0.05). CONCLUSIONS:
      These data suggest that apolipoprotein E genotype, especially the presence of an
      epsilon4 allele, is more memorable than a numeric risk estimate for Alzheimer's
      disease. Participants recalled genotype information in a more simplified, binary
      form. Health professionals testing for complex disorders such as Alzheimer's
      disease must find an appropriate balance between communicating risk in an
      understandable format and addressing the probabilistic nature of the information.

PMID- 17172938
TI  - Evaluation of family history as a risk factor and screening tool for detecting
      undiagnosed diabetes in a nationally representative survey population.
AB  - PURPOSE: We examined the utility of a three-level familial risk stratification
      system as a screening tool for diabetes in a nationally representative sample of
      the U.S. adult population. METHODS: National Health and Nutrition Examination
      Survey data were used to assess the prevalence and distribution of familial risk
      for diabetes, the association between three levels of familial risk and
      undiagnosed diabetes, and the use of familial risk as a screening tool for
      diabetes, alone and in combination with body mass index and age. RESULTS: The
      prevalence of undiagnosed diabetes was 3% and increased with increasing familial
      risk (average = 2%, moderate = 4%, high = 10%). High familial risk was
      significantly associated with undiagnosed diabetes (adjusted odds ratio = 4.6;
      95% confidence interval: 1.9-11.3). The use of a three-tiered familial risk
      stratification for diabetes screening yielded higher specificity (94%) and
      positive predictive value (9.9%) for high familial risk than body mass index > or
      = 25 (specificity = 38%, positive predictive value = 4.2%). High familial risk
      and body mass index > or = 25 combined had higher specificity (97%) and positive
      predictive value (13.4%); the addition of age > or = 45 years further improved
      positive predictive value (21.0%) without reducing specificity. CONCLUSIONS:
      There was a strong and proportional association between familial risk and
      undiagnosed diabetes, suggesting that a three-tiered assessment of familial
      diabetes risk may increase the effectiveness of diabetes screening.

PMID- 17172939
TI  - Familial testicular cancer: interest in genetic testing among high-risk family
      members.
AB  - PURPOSE: This study is part of an ongoing National Cancer Institute
      multidisciplinary, etiologically-focused, cross-sectional study of Familial
      Testicular Cancer (FTC). The current report targets interest in clinical genetic
      testing for susceptibility to FTC. METHODS: Demographics, knowledge, health
      beliefs, and psychological and social factors were evaluated as covariates
      related to interest in genetic testing. RESULTS: The majority (66%) of 229
      participants (64 affected men, 66 unaffected men, and 99 women) from 47 multiple
      case FTC families expressed interest in having a genetic test within 6 months,
      should such a test become available. Interest was similar among the three
      subgroups mentioned above. Worries about insurance discrimination based on
      genetic test results were associated with a significantly lower interest in
      testing. Alternatively, participants were more likely to be interested in genetic
      testing if they were younger and had higher levels of family support, a
      physician's recommendation supporting testing, cancer distress, and a need for
      information to inform the health care of their children. CONCLUSIONS: This study
      reveals social and relationship factors that FTC survivors and their relatives
      considered important when contemplating the use of new genetic technologies. This
      is the first study describing hypothetical interest in genetic testing for
      familial testicular cancer.

PMID- 17172940
TI  - Genetic services for men: the preferences of men with a family history of
      prostate cancer.
AB  - PURPOSE: Men have a lower uptake of genetic services than women; however, the
      specific needs and preferences of men at risk of genetic conditions other than
      hereditary breast ovarian cancer are not known. We ascertain the information
      preferences of men with a family history of prostate cancer. METHODS: Unaffected
      men and their partners were administered a written questionnaire. RESULTS:
      Responses were received from 280 men (response rate: 59.2%) and 174 partners
      (response rate: 74%). Most men (59.6%) reported having insufficient information
      about their risk and wanted further information about personal risk (93.2%) and
      risk management (93.6%). Strikingly, 56.3% preferred to receive information
      related only to positive outcomes. Urologists were the preferred source of
      information, but there was considerable interest in a multidisciplinary service
      approach significantly associated with the number of affected relatives (odds
      ratio = 1.94, P < .002). Partners' level of concern was not associated with
      interest in multidisciplinary services, satisfaction with information, or support
      received. CONCLUSIONS: Delivering services to men at risk will require a
      multifaceted approach by primary care providers and specialists. Challenges
      include meeting men's expectations in the face of uncertain medical knowledge,
      engaging those at high risk in multidisciplinary services, and delivering
      tailored information to those at lower risk.

PMID- 17172941
TI  - A focus group study of consumer attitudes toward genetic testing and newborn
      screening for deafness.
AB  - PURPOSE: Progress in identifying genes for deafness together with implementation
      of universal audiologic screening of newborns has provided the opportunity for
      more widespread use of molecular tests to detect genetic forms of hearing loss.
      Efforts to assess consumer attitudes toward these advances have lagged behind.
      METHODS: Consumer focus groups were held to explore attitudes toward genetic
      advances and technologies for hearing loss, views about newborn hearing
      screening, and reactions to the idea of adding molecular screening for hearing
      loss at birth. Focus group discussions were recorded, transcribed and analyzed.
      RESULTS: Five focus groups with 44 participants including hearing parents of deaf
      children, deaf parents and young deaf adults were held. Focus group participants
      supported the use of genetic tests to identify the etiology of hearing loss but
      were concerned that genetic information might influence reproductive decisions.
      Molecular newborn screening was advocated by some; however, others expressed
      concern about its effectiveness. CONCLUSION: Documenting the attitudes of parents
      and other consumers toward genetic technologies establishes the framework for
      discussions on the appropriateness of molecular newborn screening for hearing
      loss and informs specialists about potential areas of public education necessary
      prior to the implementation of such screening.

PMID- 17172942
TI  - Increased MECP2 gene copy number as the result of genomic duplication in
      neurodevelopmentally delayed males.
AB  - PURPOSE: Mutations in the MECP2 gene are associated with Rett syndrome, an X
      linked mental retardation disorder in females. Mutations also cause variable
      neurodevelopmental phenotypes in rare affected males. Recent clinical testing for
      MECP2 gene rearrangements revealed that entire MECP2 gene duplication occurs in
      some males manifesting a progressive neurodevelopmental syndrome. METHODS:
      Clinical testing through quantitative DNA methods and chromosomal microarray
      analysis in our laboratories identified seven male patients with increased MECP2
      gene copy number. RESULTS: Duplication of the entire MECP2 gene was found in six
      patients, and MECP2 triplication was found in one patient with the most severe
      phenotype. The Xq28 duplications observed in these males are unique and vary in
      size from approximately 200 kb to 2.2 Mb. Three of the mothers who were tested
      were asymptomatic duplication carriers with skewed X-inactivation. In silico
      analysis of the Xq28 flanking region showed numerous low-copy repeats with
      potential roles in recombination. CONCLUSIONS: These collective data suggest that
      increased MECP2 gene copy number is mainly responsible for the neurodevelopmental
      phenotypes in these males. These findings underscore the allelic and phenotypic
      heterogeneity associated with the MECP2 gene and highlight the value of molecular
      analysis for patient diagnosis, family members at risk, and genetic counseling.

PMID- 17172943
TI  - National collaborative study groups: structure, benefits gained and potential for
      rare genetic diseases.

PMID- 17172944
TI  - Creating partnerships and improving health care: the role of genetic advocacy
      groups.

PMID- 17172945
TI  - Today's professional symbiosis.

PMID- 17172946
TI  - Bisphosphonate therapy.

PMID- 17172947
TI  - Cardinal rules of implant case presentation.

PMID- 17172948
TI  - Consensus conference on immediate loading: the single tooth and partial
      edentulous areas.
AB  - PURPOSE: A consensus conference was held to determine what the parameters should
      be for the immediate functional loading of the single-tooth implant restoration
      and short-span fixed implant-supported bridgework. MATERIALS: Forty-one
      clinicians and researchers presented cases and situations relating to the topic.
      A panel then distilled questions that were presented to the audience (430) at
      large. Answers were gleaned to formulate a consensus. RESULTS: Ten distinct
      answers evolved that constituted the essence of guidelines for clinicians to be
      aware of when undertaking immediate loading. These guidelines are contained
      within the body of the text. CONCLUSIONS: Extreme caution and adherence to a
      universal generic protocol are suggested for clinicians who are involved with
      single-tooth and short-span multiple-teeth implant replacements as related to
      immediate loading as defined within this text.

PMID- 17172949
TI  - Piezosurgery: basics and possibilities.
AB  - Useful in a variety of oral surgery procedures, piezosurgery has therapeutic
      features that include a micrometric cut (precise and secure action to limit
      tissue damage, especially to osteocytes), a selective cut (affecting mineralized
      tissues, but not surrounding soft tissues), and a clear surgical site (the result
      of the cavitation effect created by an irrigation/cooling solution and
      oscillating tip). Because the instrument's tip vibrates at different ultrasonic
      frequencies, since hard and soft tissues are cut at different frequencies, a
      "selective cut" enables the clinician to cut hard tissues while sparing fine
      anatomical structures (e.g., schneiderian membrane, nerve tissue). An oscillating
      tip drives the cooling-irrigation fluid, making it possible to obtain effective
      cooling as well as higher visibility (via cavitation effect) compared to
      conventional surgical instruments (rotating burs and oscillating saws), even in
      deep spaces. As a result, implantology surgical techniques such as bone
      harvesting (chips and blocks), crestal bone splitting, and sinus floor elevation
      can be performed with greater ease and safety.

PMID- 17172950
TI  - Dental implant success-failure analysis: a concept of implant vulnerability.
AB  - This article shows the factors of importance in the long-term success and failure
      of oral implants based on literature review. Many factors are attributed to the
      failure of dental implants. The critical components leading to early and late
      implant failures are evaluated. The behavior of natural teeth and implants is
      compared in healthy and unfavorable local and systemic conditions. Similarities
      and differences among dental implants, healthy natural teeth, and ankylosed teeth
      are examined. Based on this comparison, the author attempts to draw a conclusion
      on the vulnerability of dental implants and their prognosis. The importance of
      ongoing clinical supervision of a patient's implant condition with a good recall
      program and the necessity to accumulate clinical data concerning implant failures
      over an extended period of time in a standardized manner are emphasized. It is
      also suggested that implant practitioners avoid giving guarantees of long-term
      implant success to their patients.

PMID- 17172951
TI  - A cast metal core for a deformed implant body: case report.
AB  - The present report consists of a clinical evaluation of an osseointegrated
      implant using a cast metal core instead of abutment for a deformed implant body.
      The intramobile connector insert for the implant in the mandibular left first
      premolar region broke 7 years after the superstructure was attached to the
      implant system. The intramobile connector insert was replaced, and the prosthesis
      was reattached, but the new intramobile connector insert broke again 2 weeks
      later. A thorough examination confirmed deformation of the upper section of the
      implant body in the mandibular left first molar region. Breakage of the new
      intramobile connector insert in the mandibular left first premolar region was
      believed to be due to deformation of the implant body in the mandibular left
      first molar region. Therefore, a cast metal core was used to deal with the
      deformation of the implant body in this region. Although slight bone resorption
      was observed around the implant body after 5 years, no major problems were found
      in the implant body itself.

PMID- 17172952
TI  - Medical contraindications to implant therapy: part I: absolute contraindications.
AB  - In order to ensure implant success, it is essential to select patients who do not
      possess local or systemic contraindications to therapy. Hence, it is the purpose
      of this paper to review the medical diseases that reportedly preclude
      conventional dental implant treatment. Absolute contraindications to implant
      rehabilitation include recent myocardial infarction and cerebrovascular accident,
      valvular prosthesis surgery, immunosuppression, bleeding issues, active treatment
      of malignancy, drug abuse, psychiatric illness, as well as intravenous
      bisphosphonate use. Any of these conditions bar elective oral surgery, and
      require judicious monitoring by the physician as well as the dental provider.
      Noncompliance to the suggested protocol may, in the worst possible case, result
      in patient mortality.

PMID- 17172954
TI  - Rehabilitation of maxillary edentulism with implant-supported milled-bar
      prostheses.
AB  - Implantology has allowed more options for rehabilitation of complete and
      partially edentulous patients. The professional should describe all possible
      alternatives to the patient, addressing all the positive and negative aspects of
      each possibility, such as treatment time, complexity of surgical procedures, and
      the final cost. The patient should select the best cost-benefit relationship
      because fixed prostheses are often not the option of choice for the patient. The
      aim of this article is to present one possible treatment option for the
      completely edentulous patient by use of implants to support and retain a
      removable complete or partial prosthesis. The clinical situations were
      rehabilitated by the use of a milled bar screwed to the implants to support a
      removable prosthesis with attachments and a milled metallic groove, which provide
      many advantages to the patient.

PMID- 17172953
TI  - De novo grown bone on exposed implant surfaces using photodynamic therapy and
      recombinant human bone morphogenetic protein-2: case report.
AB  - The reconstruction of bone on exposed implant surfaces requires an almost
      complete elimination of attached bacteria. Only then is new bone growth possible.
      This case report describes a new way to kill biofilms with photodynamic therapy
      and to augment bone by using recombinant human bone morphogenetic protein-2.
      Though the new technique of bone tissue engineering causes some problems, new
      bone growth on uncovered implant surfaces is successful to a large extent.

PMID- 17172955
TI  - Saliva and dental implants.
AB  - This is a review and update of the: (1) interaction of dental implants with the
      environment, and (2) effects of salivary contamination on the load of implant
      prostheses.

PMID- 17172957
TI  - Bone regeneration around implants using spherical and granular forms of bioactive
      glass particles.
AB  - PURPOSE: It has been reported that previous Biogran (3i Implant Innovations,
      Inc., Palm Beach Gardens, FL) can be converted in vitro into hydroxyapatite
      (Biogran II) to accelerate new bone formation. The purpose of this study was to
      evaluate the bone regeneration around implants placed in critical-sized defects
      in rabbit tibia using granular and spherical forms of Biogran II in regards to
      implant contact, bone-to-graft contact, bone graft area, and total bone volume.
      MATERIALS AND METHODS: Twelve adult New Zealand rabbits were used, offering 24
      surgical sites (1 in each tibia), where 6-mm round defects were created allowing
      the homocentric insertion of a screw type experimental implant with Osseotite (3i
      Implant Innovations, Inc.) surface. Half of the defects (group A) were filled up
      with spherical and half (group B) with granular forms of Biogran II. Ossix (3i
      Implant Innovations, Inc.) membranes covered the surgical sites. RESULTS: The
      histological evaluation after 8 weeks showed new bone formation in both groups,
      without any statistically significant differences in regards to bone-to-implant
      contact, bone-to-graft contact, bone graft area, and bone volume. Both
      dissolution of the outer shell and inner silica gel of the particles were
      observed mostly in spherical particles. In addition, new bone formation within
      the protected pouch interconnected with the surrounding new bone was observed
      exclusively in spherical particles of Biogran II. CONCLUSION: Faster dissolution
      of both outer and inner portions of spherical particles of Biogran II led to
      better integration with the surrounding new bone during an 8-week period of
      healing.

PMID- 17172956
TI  - Effect of glucocorticoid-induced osteoporotic-like conditions on osteoblast cell
      attachment to implant surface microtopographies.
AB  - OBJECTIVES: The objectives of this work were to: (1) establish methodology for
      pretreating osteoblast-like cells in vitro with dexamethasone to cause
      glucocorticoid-induced osteoporosis, (2) perform quantitative and qualitative
      assessments of cellular attachment of osteoporosis-like osteoblasts when grown on
      implant surfaces of differing roughness, (3) and explore the hypothesis that
      dexamethasone-treated osteoblasts have altered cell attachment properties by
      focal adhesion disassembly and decreased tyrosine phosphorylation of the focal
      adhesion tyrosine kinase. METHODS: Osteoblasts were cultured with dexamethasone
      (10(-7) and 10(-6) M) for up to 4 days of incubation to induce osteoporosis-like
      conditions. Cellular attachment assays demonstrated the effect of dexamethasone
      treatments on cellular attachment properties of osteoblasts. Qualitative data
      were obtained utilizing immunofluorescent microscopy and Western blotting. Focal
      adhesion kinase (FAK) immunoprecipitation and tyrosine-phosphorylation Western
      blots were obtained from dexamethasone-treated human embryonic palatal
      mesenchymal- 1486 osteoblast cultures supplemented with ascorbate and beta
      glycerol phosphate medium. RESULTS: Cellular attachment was significantly greater
      (P < 0.05) with non-dexamethasone-treated osteoblasts (92%) as compared to
      dexamethasone-treated osteoblasts after 1 (72%), 2 (63%), and 4 days (53%) of
      exposure. Dexamethasone-treated osteoblasts were viable and capable of
      proliferation, suggesting that the reduction of cellular attachment may be
      related to these cell adhesion processes. Immunofluorescent microscopy of both
      dexamethasone-treated osteoblasts and non-dexamethasone-treated osteoblasts
      failed to show any relative difference in the disassembly of focal adhesions and
      actin filaments. Extended dexamethasone treatment periods (up to 3 weeks) showed
      changes in the levels of FAK and FAK-phosphotyrosine in human embryonic palatal
      mesenchymal-1486 osteoblasts. CONCLUSIONS: The protocol used in this study
      demonstrated a glucocorticoid-induced osteoporosis-like suppression of
      osteoblasts. FAK disassembly was not a significant factor in short period;
      however, FAK protein levels and phosphotyrosine signaling on FAK were affected
      after 1-week exposure to dexamethasone. Phosphorylated FAK was not associated
      with the rise in the level of FAK, further indicating the possibility of FAK
      involvement in reduced cell attachment.

PMID- 17172958
TI  - Survival of immediately loaded dental implants in deficient alveolar bone sites
      augmented with beta-tricalcium phosphate.
AB  - PURPOSE: Dental implant placement in atrophic alveolar ridges often necessitates
      grafting procedures, followed by immediate or delayed implant placement. This
      study assessed the survival of immediately loaded dental implants placed in
      deficient alveolar bone sites at bone grafting. MATERIALS: From 1999 to May 2002,
      1 operator (A.P.) inserted 1065 implants (607 in mandibles, 458 in maxillae) into
      338 partially edentulous patients. Most implants were placed into compromised
      residual ridges or prepared tooth extraction sockets. Implants placed in
      augmented areas were splinted to implants in nonaugmented sites for stability. In
      all cases, beta-tricalcium phosphate was mixed with blood from the surgical site
      to augment the ridge level or fill spaces between the implant and socket wall.
      When indicated, the same materials were used for sinus floor augmentation. All
      implants were tapered screws with roughened surfaces, primarily (75%) from 1
      manufacturer. One of the authors (Z.O.) prosthetically restored a total of 189
      implants that were placed in 35 patients. In this group of patients, complete
      restorative data were available. All implants were monitored for 12-48 months
      (mean = 19.2; median = 24). RESULTS: A total of 1039 implants survived, and 26
      failed, including 5 in the anterior mandible and 21 in the maxillae. In the
      restorative group, 186 implants survived, and 3 maxillary implants failed. All
      implant failures in this study occurred in the augmented sites. CONCLUSION:
      Within the limitations of this study, immediate loading of splinted implants in
      augmented sites is a predictable procedure.

PMID- 17172959
TI  - Position of the mental foramen in a Korean population: a clinical and
      radiographic study.
AB  - PURPOSE: The purpose of this study was to improve the treatment methods for the
      mental foramen by comparing the directly measured values with the radiographic
      measured values. MATERIALS AND METHODS: One hundred and twelve mental foramina
      (72 males, 40 females) that were exposed during the operation were examined. The
      patients' age ranged from 12 to 69 years, with a mean age of 41.8 years. All
      patients had fully erupted lower premolars. The horizontal and vertical locations
      were evaluated with both direct and radiographic measurements. RESULTS: In 72
      patients (64.3%), the mental foramen was below the second premolar. In 26.8%, it
      was between the first and second premolar, and in 8.9%, it was below the first
      premolar. By radiographic readings,most of the mental foramina were found to be
      below the second premolar (62.5%). The average distance between the cusp tip and
      the superior border of the mental foramen by direct measurement was 23.42 mm and
      25.69 mm in the panoramic view. The mean distance between the superior border of
      the mental foramen and the bottom of the mandible was 14.33 mm by direct
      measurement and 16.52 mm by radiographic measurements. CONCLUSION: It is
      important to know the position of the mental foramen for the placement of
      osseointegrated implants in the mandibular premolar region. The position of the
      mental foramen of Koreans is closer to the cusp tips of lower premolars than
      Westerners.

PMID- 17172960
TI  - Implant-supported prosthetic applications upon development of children and
      adolescents: a pilot study in pigs.
AB  - PURPOSE: The purpose of this study is the investigation of the application of
      implant-supported prosthetic restorations using 2 implants supporting a fixed
      prosthesis during the physical growth and the development period of growing pigs.
      MATERIALS AND METHODS: This study was carried out on 6 male farm pigs (1 as a
      control). The effect of the 2 screw-type endosseous implants inserted into the
      premolar area on the left mandibular arches of 5 farm pigs upon the jaw was
      investigated during a 3.5-8-month growth period using cephalometric radiographs.
      The cephalographs were taken with a specially standardized cephalostat, and a
      significant test of differences between 2 partners was used to evaluate them.
      RESULTS: The study suggested that the implants showed alveolar elevation by bone
      growth but could not keep pace with the natural teeth eruptions and the bone
      growth in the region. CONCLUSION: Although the sagittal and transverse
      developments of the neighboring bone region are greater than the implant-inserted
      region, the difference in this growth can be tolerated by corrections or
      modifications of implant-supported superstructures.

PMID- 17172965
TI  - Using evidence-based design to improve outcomes.

PMID- 17172962
TI  - An in vitro analysis of implant screw torque loss with external hex and internal
      connection implant systems.
AB  - PURPOSE: The purpose of this study was to examine, in a controlled environment,
      effects of connection design upon screw stability. Implant fixtures have 2 types
      of connections to the abutment: internal connection and external hex. Four
      implant systems were tested: Bio-Lok (external hex; Bio-Lok International, Inc.,
      Deerfield Beach, FL); Zimmer (internal connection; Zimmer Dental, Carlsbad, CA);
      Nobel Biocare (external hex; Nobel Biocare USA, Inc., Yorba Linda, CA); and Astra
      Tech (internal connection; Astra Tech Inc., Waltham, MA). MATERIALS AND METHODS:
      Ten samples of each system, including base, implant, abutment, and molar crown,
      were loaded to 200 N for 1 x 10(6) cycles. Screws were tightened to
      manufacturers' recommendations,and torque audits done at 2.5 x 10(5), 5 x 10(5),
      7.5 x 10(5), and 1 x 10(6) cycles. RESULTS: The Bio-Lok samples lost an average
      of 10% of the original torque values, the Astra Tech group lost almost all of the
      torque and loosened, while the Zimmer and Nobel Biocare samples lost an average
      of 50% of the torque but did not loosen (P <or= 0.05). CONCLUSIONS: It may be
      concluded from this study that although internal connections are clinically
      favored, this study did not show any advantage relative to screw loosening.
      However, screw design may be a significant factor in loosening of the joint.

PMID- 17172967
TI  - Creating sustainability of clinical information systems: the chief nurse officer
      and nurse informatics specialist roles.

PMID- 17172961
TI  - Complications of intraoral donor site for bone grafting prior to implant
      placement.
AB  - PURPOSE: The purpose of this prospective study was to evaluate the morbidity and
      the major complications of intraoral donor sites for bone grafting prior to
      implant placement. MATERIALS: The records of 104 consecutive patients with
      indication for bone grafting prior to implant installation treated at Piracicaba
      Dental School by the Department of Oral and Maxillofacial Surgery, from June 2001
      until June 2003, were reviewed. RESULTS: One hundred three surgical procedures
      were realized, in which 40% were harvested from mandibular symphysis, 28.8% from
      mandibular ramus, and 31.2% from maxillary tuberosity. Prevalence of
      complications among intraoral donor sites was more significant after harvesting
      the mandibular symphysis. The major complication and discomfort reported by the
      patients was sensory deficit in lower lip and mental area. It was noted that 16%
      harvesting procedures involving symphysis and 8.3% involving the mandibular ramus
      area reported some sensory deficit. No complications were found involving the
      maxillary tuberosity. CONCLUSION: Complications and morbidity were smaller in the
      ramus than in symphysis, and temporary sensory disturbances were the most common
      complications, noted in both symphysis and ramus areas.

PMID- 17172968
TI  - Balanced scorecards for performance management.
AB  - Nurse administrators who manage nursing case management programs are challenged
      to demonstrate the improved quality of patient care and financial outcomes to
      their organization that result from such programs. This article introduces the
      balanced scorecard and discusses its benefits and practical concerns for adopting
      the scorecard. The balanced scorecard is a useful performance management tool
      used to both evaluate and direct case management performance in meeting
      organizational missions and strategies.

PMID- 17172969
TI  - A review of organizational culture instruments for nurse executives.
AB  - Nurse executives are aware of the complexities of organizational culture. It
      impacts the nursing work environment and patient care safety and quality. The
      authors describe several widely available tools that nurse leaders can use to
      assess organizational culture in the work environment. The psychometric and
      conceptual strengths and weaknesses of the measures are described and
      recommendations for use in nursing and patient care administration are provided.

PMID- 17172970
TI  - Describing costs related to nursing.
AB  - There is limited financial evidence describing the relationship between nursing
      staffing and patient care costs. In this analysis, the body of knowledge relating
      costs to nursing practice is described and critiqued. An improved method of
      describing costs of patient care is presented, and a comparison of costs using
      each approach illustrates how the magnitude of cost variation between 2 patients
      differs based on the approach used.

PMID- 17172971
TI  - Excellence through evidence: structures enabling clinical autonomy.
AB  - Autonomy is a multidimensional process. Clinical autonomy, the dimension in which
      patients are the primary beneficiaries, is the focus of this study. Despite high
      valuation and persistent challenges to nurses to function autonomously, the
      relationship between autonomous practice and patient outcomes has not been
      empirically established due, in large measure, to a lack of correspondence
      between concepts and measurement of autonomy and to a lack of knowledge of
      enabling structures. The purpose of the research reported here is to identify the
      structures, practices, elements in the environment, and interventions that
      nurses, nurse managers, and physicians identify as promoting staff nurse clinical
      autonomy. Implementation of these interventions would then enable clinical
      decision making at the frontline and would foster studies to determine whether
      the expected linkage between clinical autonomy and positive patient outcomes
      prevails.

PMID- 17172972
TI  - What's new in shock, January 2007?

PMID- 17172973
TI  - Serum cytokine differences in severely burned children with and without sepsis.
AB  - The aim was to determine whether serum cytokine profiling early after burn can be
      used to identify patients at high risk of developing and subsequently dying of
      sepsis. A case series study was designed to determine whether serum cytokine
      profiling allows identification of patients at highest risk of developing and
      dying of sepsis at the time of hospital admission. All patients were treated
      according to the standard of burn care at our facility. Forty-four children (1-19
      years old) with more than 40% of total body surface area and admitted within 7
      days postburn were studied. None had infections or sepsis at the time of
      admission. Serum was collected before the first operation, and concentrations of
      17 cytokines were measured. Diagnosis of sepsis was made at autopsy with
      identification of the pathogen. Fifteen patients developed sepsis and died,
      whereas 29 patients did not develop sepsis and survived. Significant elevations
      in serum interleukin (IL) 6, IL-8, IL-10, granulocyte-monocyte colony-stimulating
      factor, interferon gamma (IFN-gamma), tumor necrosis factor (TNF), and IL-12 p70
      were found at the time of admission of patients who subsequently developed and
      died of sepsis when compared with burned patients who did not develop sepsis (P <
      0.05). Multiple logistic regression analysis revealed that patients with a
      combination of elevated IL-6 and IL-12 p70 and lower TNF had an elevated risk of
      dying of sepsis. Serum IL-6, IL-8, IL-10, granulocyte-monocyte colony-stimulating
      factor, IFN-gamma, TNF, and IL-12 p70 are expressed differently in patients who
      die of sepsis versus those who never become septic. In addition, serum IL-6, IL
      12 p70, and TNF can be used to identify burned patients who are at high risk of
      death from sepsis.

PMID- 17172974
TI  - Myocardial structural changes in long-term human severe sepsis/septic shock may
      be responsible for cardiac dysfunction.
AB  - The present investigation sought to determine the cellular mechanisms directly
      dependent on long-term severe sepsis/septic shock that could lead to myocardial
      structural changes in humans. Human hearts from eight cases of long-term severe
      sepsis/septic shock arising from infection, as defined by the ACCP/SCCM Consensus
      Conference; eight cases of acute necrotizing pancreatitis and acute lung injury,
      a noninfectious pathologic cause of systemic inflammatory response; and three
      cases of accidental death without thoracic injury selected from autopsies were
      studied. Transmural blocks of myocardial tissue were excised from the middle
      portion of the left ventricular free wall and were fixed in formalin or were
      frozen. Histochemical and immunohistochemical methods were used to evaluate the
      cross-striations of the myocardial cells, the number and size of interstitial
      macrophages, the intracardiomyocyte accumulation of lipid, the actin/myosin
      contractile apparatus, and the expression of iNOS, nitrotyrosine, and TNF-alpha
      in the myocardia of septic and control hearts. Greater interstitial cellular
      infiltration composed of larger and elongated macrophages and TNF-alpha protein
      expression in myofibers, interstitial macrophage cell types, and smooth muscle
      cells and endothelial cell in the vessels; intracardiomyocyte lipid accumulation;
      scattered foci of actin/myosin contractile apparatus disruption; and increased
      expression for iNOS and nitrotyrosine in myocytes and interstitial macrophage
      cell types could be observed in long-term human septic myocardium as compared
      with normal and acute pancreatitis control myocardia. These findings give support
      to an opinion that structural changes could be responsible for long-term sepsis
      induced myocardial dysfunction. The higher number of macrophages, most of them
      with morphological features of "activation," and TNF-alpha protein expression
      could favor the reduction of cardiac function in septic hearts. The intramyocyte
      lipid accumulation in these hearts very likely reflects myocardium ventricular
      contractile dysfunction. In addition, the increased expression of iNOS and the
      evidence for the significant presence of peroxynitrite in cardiomyocytes and
      interstitial macrophage cell types suggest that oxidative damage may play a role
      in actin/myosin disruption in the hearts of septic patients.

PMID- 17172975
TI  - Vitamin E inhibits endotoxin-mediated transport of phosphatases to lipid rafts.
AB  - The production and release of inflammatory mediators is regulated by the
      coordinated activity of kinases and phosphatases. These proteins are known to
      regulate one another through an unknown mechanism. Previously, we have
      demonstrated that autocrine release of oxidants regulates macrophage activation
      in a similar fashion. The purpose of this study is to determine if attenuated
      oxidant activity by antioxidant exposure can regulate endotoxin-mediated kinase
      and phosphatase activity. Human promonocytic THP-1 cells were stimulated with
      lipopolysaccharide. Selected cells were pretreated with alpha-tocopherol
      succinate, LY294002, or an AKT inhibitor (1L-6-hydroxymethyl-chiro-inositol 2-(R)
      2-O-methyl-3-O-octadecylcarbonate). Lipid raft and cellular protein were analyzed
      for lipid raft toll-like receptor 4 (TLR4) receptor formation and mitogen
      activated protein kinase (MAPK) activation. Harvested supernatants were analyzed
      for tumor necrosis factor (TNF)-alpha production. Lipopolysaccharide stimulation
      led to the lipid raft mobilization of TLR4 and heat shock protein 70. This was
      followed by lipid raft mobilization of SH related complex homology 2 domain
      containing inositol-5-phosphate (SHIP), activation of the MAPK, and production of
      TNF-alpha. Pretreatment with alpha-tocopherol succinate did not affect
      mobilization of TLR4 or heat shock protein 70, but did result in attenuated
      mobilization of SHIP, activation of the MAPK, and production of TNF-alpha. In
      addition, alpha-tocopherol succinate was associated with increased activation of
      the counter-regulatory kinase protein kinase B. Pretreatment with LY294002 or 1L
      6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate reversed
      the effects of alpha-tocopherol succinate. Thus, it seems that endotoxin-mediated
      activation requires the coordinated activity of kinases and phosphatases.
      Antioxidant exposure in the form of vitamin E seems to attenuate endotoxin
      mediated SHIP activation resulting in increased AKT activity, and attenuated MAPK
      activation and TNF-alpha production.

PMID- 17172976
TI  - Effects of adenosine on functions of polymorphonuclear leukocytes from patients
      with septic shock.
AB  - Inasmuch as polymorphonuclear leukocytes (PMNs) play a major role in
      antibacterial defense but can also cause substantial tissue injury, drugs are
      needed which are able to attenuate tissue-toxic PMN reactions without inhibiting
      bactericidal mechanisms. Adenosine as a retaliatory metabolite is produced in
      response to metabolically unfavorable conditions like inflammation. However, it
      is not known whether adenosine can selectively downregulate adverse PMN reactions
      in sepsis. In this prospective clinical study, we characterized the effects of
      adenosine ex vivo on PMN functions in patients with septic shock ([SS] n = 33)
      and healthy volunteers ([HV] n = 33). The PMNs were primed by tumor necrosis
      factor-alpha (TNF-alpha) and subsequently stimulated with N-formyl methionyl
      leucyl-phenylalanine (fMLP) to test for the formation of hydrogen peroxide (H2O2)
      in response to soluble inflammatory stimuli. The PMNs were also challenged by
      opsonized zymosan particles to assess adhesion, phagocytosis, and the associated
      H2O2 production. As compared with HV, PMNs from SS patients showed strongly
      enhanced tissue-toxic H2O2 production elicited by TNF-alpha/fMLP. Increasing
      concentrations of adenosine dose-dependently reduced this tissue-toxic H2O2
      production in both groups with a half-maximal inhibitory concentration of 25
      nmol/L and 114 nmol/L in HV and SS patients, respectively. This 4.6-fold decrease
      in the adenosine-mediated inhibition of PMNs from patients with septic shock was
      compensated by a 3-fold increase in the plasma concentrations of the nucleoside
      (HV, 42.5 +/- 2.9 nmol/L vs. SS, 125.6 +/- 18.2 nmol/L; mean +/- SEM). When the
      effects of adenosine were tested at a very high A2A receptor saturating
      concentration of 10 mol/L, neither adhesion, phagocytosis, nor the associated
      H2O2 production induced by opsonized zymosan was affected in both groups. These
      results were confirmed by the highly selective A2A agonist, CGS21680.Thus,
      adenosine or A2A agonists may be useful to selectively inhibit the potentially
      tissue-toxic H2O2 production elicited by soluble inflammatory mediators in
      patients with septic shock.

PMID- 17172977
TI  - Sodium chloride inhibits cytokine production by lipopolysaccharide-stimulated
      human neutrophils and mononuclear cells.
AB  - Hypertonic sodium chloride (NaCl) solution has been shown to have beneficial
      effects on patients with hypovolemic shock. Therapy with hypertonic saline seems
      to neutralize or minimize the deleterious immune responses in these patients. In
      this study, we addressed how hypertonic NaCl solution affects the release of
      cytokines by isolated human blood cells. We examined the effect of NaCl on tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-1beta, and IL-1 receptor
      antagonist released by human neutrophils and mononuclear cells under
      nonstimulated and LPS-stimulated conditions. Cells isolated from healthy donors
      were cultured in the presence or absence of lipopolysaccharide (LPS). Cytokine
      concentrations were measured by enzyme-linked immunosorbent assay in culture
      supernatants. The addition of NaCl lowered the production of IL-8, TNF-alpha, and
      IL-1 receptor antagonist by neutrophils, and IL-8 and IL-1beta by mononuclear
      cells stimulated with LPS. This effect was not observed when NaCl solution was
      replaced by a solution of potassium iodide in the same conditions. The decreased
      production of cytokines in the presence of hypertonic saline was not caused by
      cell death. Our findings support the proposal that the modulation of leukocyte
      inflammatory response by NaCl occurs by an electrolyte-specific effect in
      addition to the hyperosmolarity. Furthermore, the results of this study support
      the therapeutic use of appropriate doses of i.v. NaCl solutions to minimize
      tissue injury characterized by neutrophil and mononuclear cell infiltration into
      tissues in post-traumatic patients.

PMID- 17172978
TI  - Selective protein kinase C inhibition attenuates pulmonary artery cytokine
      expression without affecting hypoxic pulmonary vasoconstriction.
AB  - Hypoxic pulmonary vasoconstriction may be an adaptive response to shunt blood to
      well-oxygenated areas of the lung, but hypoxia-induced inflammatory cytokine
      production leads to acute lung injury. We have previously shown that protein
      kinase C (PKC) mediates both hypoxic pulmonary vasoconstriction and inflammatory
      cytokine expression from the pulmonary artery; however, the effect of specific
      PKC isoform inhibition is currently unknown. We hypothesized that inhibition of
      classical PKC (cPKC) isoforms would attenuate hypoxic pulmonary vasoconstriction
      and downregulate hypoxia-induced pulmonary artery cytokine expression. To study
      this, isometric force displacement was measured in isolated rat pulmonary artery
      rings (n = 6 per group) during hypoxia (95% N2/5% CO2) in the presence of the
      nonspecific PKC inhibitor bisindolylmaleimide (1 micromol/L), the cPKC inhibitor
      Go 6976 (1 - 10 micromol/L), or vehicle (dimethyl sulfoxide, 0.001%). After 60
      min of hypoxia, pulmonary artery rings were analyzed for tumor necrosis factor
      (TNF) alpha and interleukin (IL) 1beta messenger RNA via reverse transcriptase
      polymerase chain reaction. Nonspecific PKC inhibition (bisindolylmaleimide)
      significantly attenuated hypoxic pulmonary vasoconstriction (44.59 +/- 10.52% vs.
      87.06 +/- 10.91% vehicle; P < 0.001) and downregulated hypoxia-induced expression
      of pulmonary artery TNF-alpha. Specific cPKC inhibition (Go 6976) attenuated
      pulmonary artery TNF-alpha expression but had no effect on hypoxic pulmonary
      vasoconstriction. These data are indicative of the following: (1) nonspecific PKC
      inhibition attenuates both hypoxic pulmonary vasoconstriction and pulmonary
      artery TNF-alpha expression, (2) cPKC inhibition downregulates hypoxia-induced
      pulmonary artery TNF-alpha expression but has no effect on hypoxic pulmonary
      vasoconstriction, and (3) hypoxic pulmonary vasoconstriction and hypoxia-induced
      pulmonary artery cytokine expression are independent processes.

PMID- 17172979
TI  - Elucidation of toll-like receptor and adapter protein signaling in vascular
      dysfunction induced by gram-positive Staphylococcus aureus or gram-negative
      Escherichia coli.
AB  - Pathogens contain specific pathogen-associated molecular patterns, which activate
      pattern recognition receptors of the innate immune system such as Toll-like
      receptors (TLRs). Although there is a clear evidence of how macrophages sense
      pathogens, we know less about such processes in vessels. This is critical to
      understand because activation of vascular cells and the subsequent induction of
      inflammatory genes by bacteria are crucial events in the development of septic
      shock. In the current study we have used genetically modified mice to investigate
      the role of TLRs, adapter proteins, tumor necrosis factor alpha (TNFalpha), and
      nitric oxide synthase II (NOSII) in vascular dysfunction induced by Gram-positive
      (Staphylococcus aureus) or Gram-negative (Escherichia coli) bacteria. Our data
      show that Gram-positive S. aureus or Gram-negative E. coli causes vascular
      dysfunction via the induction of NOSII. For S. aureus, this process requires
      TLR2, TLR6, myeloid differentiation factor 88 (MyD88) adapter-like, MyD88, and
      TNF, but not TLR4 or TLR1. Vascular dysfunction induced by E. coli requires TLR4
      but has no requirement for TLR2, TLR1, TLR6, or TNF, and a partial but incomplete
      requirement of MyD88 and TIR domain-containing adapter inducing interferon-beta.
      Staphylococcus aureus induced NOSII protein expression in vascular smooth muscle
      cells but not in macrophages, whereas E. coli induced NOSII in both cell types.
      Our data are the first to establish the definitive roles of specific TLRs in the
      sensing of Gram-positive and Gram-negative bacteria by vessels and demonstrate
      that macrophages and blood vessels may differ in their response to pathogens.

PMID- 17172980
TI  - Lysophosphatidic acid reduces the organ injury caused by endotoxemia-a role for G
      protein-coupled receptors and peroxisome proliferator-activated receptor-gamma.
AB  - Exogenous lysophosphatidic acid (LPA) has been shown to beneficial in renal
      ischemia/reperfusion injury, wound healing and colitis. LPA acts via specific G
      protein-coupled receptors and also peroxisome proliferator-activated receptor
      gamma (PPAR-gamma). However, activation of PPAR-gamma is dependent on the
      presence of an unsaturated acyl chain. Here we investigate the effects of
      saturated LPA (18:0) and unsaturated LPA (18:1) on the organ injury associated
      with endotoxemia and the receptors mediating LPA activity. Male Wistar rats
      received either lipopolysaccharide (LPS, 6 mg/kg i.v.) or vehicle. The PPAR-gamma
      antagonist GW9662 (1 mg/kg i.v.), the LPA receptor antagonist Ki16425 (0.5 mg/kg
      i.v.) or vehicle was administered 30 min after LPS. LPA 18:0 or LPA 18:1 (1 mg/kg
      i.v.) or vehicle was administered 1 h after injection of LPS. Endotoxemia for 6 h
      resulted in an increase in serum levels of aspartate aminotransferase, alanine
      aminotransferase and creatine kinase. Therapeutic administration of LPA 18:0 or
      18:1 reduced the organ injury caused by LPS. LPA 18:0 also attenuated the
      increase in plasma IL-1beta caused by LPS. Ki16425, but not GW9662, attenuated
      the beneficial effects of LPA 18:0, however, Ki16425 and GW9662 attenuated the
      beneficial effects of 18:1. In conclusion, LPA reduces the organ injury caused by
      endotoxemia in the rat. Thus, LPA may be useful in the treatment of shock of
      various aetiologies. The mechanism of action is related to acyl chain saturation,
      with LPA 18:0 acting via G-protein-coupled receptors and LPA 18:1 acting via G
      protein-coupled receptors and PPAR-gamma.

PMID- 17172981
TI  - Role of Janus kinase/signal transducer and activator of transcription pathway in
      regulation of expression and inflammation-promoting activity of high mobility
      group box protein 1 in rat peritoneal macrophages.
AB  - Signal transduction mechanism in the regulation of high mobility group box
      protein 1 (HMGB1) has not yet been well elucidated. Our data showed for the first
      time that Janus kinase-signal transduction and activator of transcription
      (JAK/STAT) pathway played a major role in the regulation of expression and
      inflammatory effect of HMGB1. The study was carried out in the following
      sequence. Firstly, the role of JAK/STAT pathway in the regulation of expression
      of HMGB1 was examined. After stimulation with 75 ng/mL LPS in vitro, significant
      increases in HMGB1 expression and prompt activation of JAK/STAT pathway were
      demonstrated in cultured macrophages. On the other hand, administration of AG490
      (specific inhibitor for JAK2), fludarabine (specific inhibitor for STAT1) or
      rapamycin (specific inhibitor for STAT3) markedly suppressed HMGB1 expression.
      Secondly, the role of JAK/STAT pathway in the regulation of TNF-alpha expression
      induced by HMGB1 was examined. When macrophages were stimulated with 10 microg/mL
      HMGB1 in vitro, significant increases in TNF-alpha expression and prompt
      activation of JAK/STAT pathway were demonstrated, whereas inhibitors of JAK/STAT
      pathway significantly suppressed TNF-alpha expression. Taken together, our data
      strongly indicated that expression and inflammatory effect of HMGB1 could be
      mediated by JAK/STAT pathway and suggested a possible clinical strategy to
      control an inflammatory effect of HMGB1 in sepsis.

PMID- 17172982
TI  - Effects of combining inducible nitric oxide synthase inhibitor and radical
      scavenger during porcine bacteremia.
AB  - Complex interactions of nitric oxide and other free radicals have been implicated
      in the pathogenesis of sepsis and organ dysfunction. We hypothesized that
      simultaneous inducible nitric oxide synthase inhibition (L-N6-[1-iminoethyl]
      lysine [L-NIL]) and neutralization of superoxide (O2-) (4-hydroxy-2,2,6,6
      tetramethylpiperidine-N-oxyl [Tempol]) would protect from detrimental
      consequences of long-term, volume-resuscitated, hyperdynamic porcine bacteremia.
      In this prospective, randomized, controlled experimental study, 16 anesthetized,
      mechanically ventilated and instrumented pigs were exposed to 24 h of continuous
      infusion of live Pseudomonas aeruginosa. After 12 h of hyperdynamic sepsis,
      animals were randomized to receive either vehicle (control, n = 8) or combination
      of L-NIL and Tempol (n = 8). Systemic and hepatosplanchnic hemodynamics, oxygen
      exchange, metabolism, ileal mucosal microcirculation and tonometry, oxidative
      stress and coagulation parameters were assessed before, 12, 18, and 24 h of P.
      aeruginosa infusion. Combined treatment inhibited sepsis-induced increase in
      plasma nitrate/nitrite, 8-isoprostane, and thiobarbituric acid reactive species
      concentrations, prevented hypotension, and reversed hyperdynamic circulation.
      Despite lower intestinal macrocirculation, combined regimen attenuated the
      otherwise progressive deterioration in ileal mucosal microcirculation and
      prevented mucosal acidosis. Treatment substantially attenuated mesenteric and
      hepatic venous acidosis, preserved sepsis-induced impairment of hepatosplanchnic
      redox state, and prevented the development of renal dysfunction. Finally,
      coinfusion of L-NIL and Tempol largely attenuated the sepsis-induced rise in
      plasma von Willebrand factor and thrombin-antithrombin complexes. Thus,
      hemodynamic, microcirculatory, metabolic, renal, and coagulation data indicate
      that combining inducible inhibition with cell permeable O2(-) radical scavenger
      afforded significant protection in porcine sepsis, thus suggesting an important
      interactive role of O2(-) and nitric oxide in mediating organ dysfunction.

PMID- 17172984
TI  - C1-esterase inhibitor reverses functional consequences of superior mesenteric
      artery ischemia/reperfusion by limiting reperfusion injury and restoring
      microcirculatory perfusion.
AB  - Activated complement contributes significantly to reperfusion injury after
      ischemia. This study explores functional consequences of C1-esterase inhibitor
      (C1-INH) treatment after superior mesenteric artery occlusion (SMAO)/reperfusion
      using intravital microscopy. Thirty anesthetized, spontaneously breathing, male
      Sprague-Dawley rats underwent SMAO for 60 min followed by reperfusion (4 h). C1
      esterase inhibitor (100 and 200 IU/kg body weight) or saline (0.9%) was given as
      a single bolus before reperfusion. Sham-operated animals (n = 10) without SMAO
      served as controls. Systemic hemodynamics were monitored continuously, arterial
      blood gases analyzed intermittently, and leukocyte/endothelial interactions in
      the mesenteric microcirculation quantified at intervals using intravital
      microscopy. Ileal lipid-binding protein (I-LBP) levels were determined from serum
      samples with an enzyme-linked immunosorbent assay at the end of the experiments.
      C1-esterase inhibitor restored microcirculatory perfusion to baseline levels in a
      dose-dependent manner and reduced adherent leukocytes after SMAO/reperfusion to
      similar levels in both C1-INH-treated groups during reperfusion. Furthermore, C1
      INH treatment efficiently prevented metabolic acidosis, reduced the need for
      intravenous fluids to support blood pressure, and decreased I-LBP levels in a
      dose-dependent manner. Survival rates were 100% in controls and after 200 IU/kg
      C1-INH, 90% after 100 IU/kg C1-INH, and 30% in saline-treated animals. C1
      esterase inhibitor bolus infusion efficiently blunted functional consequences of
      mesenteric ischemia/reperfusion with I-LBP, proving to be a valuable serum marker
      mirroring the effect of ischemia/reperfusion and treatment at the end of the
      experiments.

PMID- 17172983
TI  - Annexin V detection of lipopolysaccharide-induced cardiac apoptosis.
AB  - Acute inflammatory response to lipopolysaccharide (LPS) exposure is typically
      associated with cardiac myocyte apoptosis, which is difficult to quantify because
      of heart tissue specificity. We report here that radioiodinated Annexin V (I
      AnxV), a specific ligand of phosphatidylserine exposed by apoptotic cells, allows
      tissue detection of apoptosis in LPS-treated rat hearts. Heart I-AnxV uptake was
      significantly increased in all cardiac territories of LPS-treated rats. In
      contrast, I-human serum albumin myocardial uptake was only slightly increased in
      LPS-treated rat hearts, suggesting limited changes in vascular protein
      permeability. Autoradiography of endotoxin-treated rat heart sections with I-AnxV
      in association with deoxynucleotidyl transferase-mediated dUTP-biotin nick-end
      labeling and caspase 3 staining allows identification of double positive cardiac
      myocytes. Inhibition of apoptosis by caspase inhibitors (i.e., ZVAD.fmk and
      DEVD.cmk) reduced I-AnxV myocardial uptake in LPS-treated rats. Eventually,
      endotoxin-treated rats displayed pathological uptake of Tc-annexin in the cardiac
      mediastinal region whereas zVAD.fmk reduced Tc-annexin mediastinal uptake. Our
      results show that radioactive I-AnxV signal emerging from LPS-treated rat hearts
      could be related to the activation of caspase-dependent apoptotic pathway in
      cardiac myocytes.

PMID- 17172985
TI  - Nonischemic lung injury by mediators from unilateral ischemic reperfused lung:
      ameliorating effect of tumor necrosis factor-alpha-converting enzyme inhibitor.
AB  - We hypothesized that the ischemic reperfused (I/R) lung expresses and liberates
      tumor necrosis factor-alpha (TNF-alpha) to injure the nonischemic lung, and that
      a TNF-alpha-converting enzyme inhibitor (TACEI) prevents injury of the
      nonischemic lung by blocking TNF-alpha liberation from the I/R lung. In isolated
      ventilated rat lungs in which differential perfusion to the right (RL) or left
      (LL) lung was feasible, LLs were selectively made ischemic (60 min) while
      maintaining perfusion to RLs, then reperfused (30 min) in a nonrecirculating
      manner with buffer solution (non-R; n = 18) or in a recirculating manner with
      buffer containing TACEI (TACEI[+]; n = 18) or without TACEI (TACEI[-]; n = 18).
      Ischemia reperfusion induced TNF-alpha messenger RNA expression in the ischemic
      LLs; the expression was highest in TACEI(+) group (P < 0.01). The expression of
      TNF-alpha, which was detected as immunofluorescence signals on CD34-positive
      endothelial cells, was observed in ischemic LLs; the highest expression being
      that in the TACEI(+) group. Wet/dry ratio and protein content in bronchoalveolar
      lavage fluid were higher in LLs than in RLs, and among the RLs, these 2
      parameters were significantly increased in the TACEI(-) group (P < 0.01) in which
      the RLs were exposed to the TNF-alpha-rich perfusate. On the other hand, protein
      content in bronchoalveolar lavage fluid of the TACEI(+) group in which RLs were
      exposed to recirculating perfusate containing little TNF-alpha was decreased to a
      level close to but still higher than that in the non-R group (P < 0.05). The
      unilateral I/R lung affected the permeability of the nonischemic lung by
      liberating mainly TNF-alpha and induced TNF-alpha, interleukin (IL)-1beta, IL-6,
      and IL-10 messenger RNA expression in the nonischemic lung. These findings
      support the idea of organ-organ interaction in which an injured organ affects a
      remote organ by liberating humoral mediators.

PMID- 17172986
TI  - The disaccharide trehalose inhibits proinflammatory phenotype activation in
      macrophages and prevents mortality in experimental septic shock.
AB  - Proinflammatory phenotype activation in macrophages (MPhis) after sepsis
      orchestrates an inflammatory response leading to multiple organ dysfunction.
      Trehalose preserves cell viability during exposure to a range of environmental
      stresses. We investigated whether trehalose may inhibit endotoxin-induced
      activation of the inflammatory phenotype in MPhis. Rat peritoneal MPhis were
      stimulated with 50 microg/mL of Salmonella enteritidis lipopolysaccharide (LPS).
      Stimulated MPhis were coincubated with trehalose (25, 50, and 100 mmol), sucrose
      (100 mmol), or RPMI alone. Macrophages cultures were used for Western blot
      analysis of extracellular-regulated kinase, c-jun-N terminal kinase, and
      inducible nitric oxide synthase; interleukin (IL) 1beta, IL-6, and tumor necrosis
      factor alpha (TNF-alpha) gene expression by real-time reverse transcriptase
      polymerase chain reaction, and supernatants for measuring the release of
      inflammatory cytokines and nitrite content. In vitro trehalose significantly
      blunted LPS-induced extracellular-regulated kinase (LPS = 21 +/- 6 integrated
      intensity; LPS + trehalose 100 mmol = 2 +/- 0.3 integrated intensity), c-jun-N
      terminal kinase (LPS = 15 +/- 5 integrated intensity; LPS + trehalose 100 mmol =
      3.5 +/- 0.9 integrated intensity), and inducible nitric oxide synthase activation
      (LPS = 12 +/- 3 integrated intensity; LPS + trehalose 100 mmol = 1 +/- 0.09
      integrated intensity), blunted IL-1beta (LPS = 5 +/- 1.9 n-folds/beta-actin; LPS
      + trehalose 100 mmol = 1.5 +/- 0.8 n-folds/beta-actin), IL-6 (LPS = 4 +/- 1.5 n
      folds/beta-actin; LPS + trehalose 100 mmol = 1.4 +/- 0.5 n-folds/beta-actin), and
      TNF-alpha (LPS = 4.2 +/- 1.6 n-folds/beta-actin; LPS + trehalose 100 mmol = 1.1
      +/- 0.7 n-folds/beta-actin) gene expression, and markedly reduced the release of
      inflammatory cytokines and nitrite content. Furthermore, in vivo trehalose
      prevented mortality in rats challenged with a lethal dose (20 mg/kg; LD90) of LPS
      (80% survival rate and 70% survival rate 24 and 72 h after LPS injection,
      respectively) and reduced serum TNF-alpha. Sucrose did not modified inflammatory
      phenotype in vitro nor in vivo protected against endotoxin-induced mortality. Our
      study suggests that trehalose inhibits proinflammatory phenotype activation in
      MPhis and prevents endotoxin-induced mortality.

PMID- 17172987
TI  - Glycogen synthase kinase 3beta inhibition reduces the development of nonseptic
      shock induced by zymosan in mice.
AB  - Glycogen synthase kinase 3 has recently been identified as a ubiquitous serine
      threonine protein kinase that participates in a multitude of cellular processes
      and plays an important role in the pathophysiology of a number of diseases. In
      the present study, we have investigated the effects of 4-benzyl-2-methyl-1,2,4
      thiadiazolidine-3,5-dione (TDZD-8), a glycogen synthase kinase 3beta inhibitor,
      on the development of nonseptic shock caused by zymosan (dose, 500 mg/kg i.p.
      suspension in saline) in mice. Organ failure and systemic inflammation in mice
      was assessed 18 h after administration of zymosan and/or TDZD-8; another group of
      mice was monitored for 12 days (for clinical score and mortality). Treatment of
      mice with TDZD-8 (dose, 10 mg/kg i.p., 1 and 6 h after zymosan administration)
      attenuated the peritoneal exudation and the migration of polymorphonuclear cells
      caused by zymosan. TDZD-8 also attenuated the lung, liver, and pancreatic injury,
      the renal dysfunction caused by zymosan, and the increase in myeloperoxidase
      activity caused by zymosan in the lung and in the intestine. Immunohistochemical
      analysis for inducible nitric oxide synthase, nitrotyrosine, poly(ADP-ribose),
      CD30, CD30 ligand, and Fas ligand revealed positive staining in lung and
      intestinal tissues obtained from zymosan-injected mice. The degree of staining
      for inducible nitric oxide synthase, nitrotyrosine, poly(ADP-ribose), CD30, CD30
      ligand, and Fas ligand were markedly reduced in tissue sections obtained from
      zymosan-injected mice that had received TDZD-8. This study provides the first
      evidence that TDZD-8 attenuates the degree of zymosan-induced, nonseptic shock in
      mice.

PMID- 17172988
TI  - Intracranial malignant meningioma with multiple spinal metastases--a case report
      and literature review: case report.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a case and review the literature
      on intracranial malignant meningioma with metastasis to the spine. SUMMARY OF
      BACKGROUND DATA: Because so few cases have been recognized and reported, the
      radiologic and pathologic assessment, pathway of metastasis, and the concepts of
      surgical resection and other palliative management of this disease are still
      controversial. METHODS: A big lobulated mass in the left frontal lobe containing
      calcifications and tumor bleeding was resected. Pathologic findings indicated
      malignant meningioma due to bone destruction and dura invasion grossly, and tumor
      cellular atypism with mitotic activity and massive tumor necrosis
      microscopically. Radiotherapy followed, and brain computed tomography revealed no
      definite evidence of recurrence. Three months later, spinal magnetic resonance
      imaging revealed multiple bone metastasis in lower T-L-S1, and pathologic
      fracture of L1 with compression of the dural sac and spinal cord. Surgical
      resection was done for decompression, fixation, and pathologic proof. RESULTS:
      Both pathologic and immunohistochemical survey found evidence consistent with
      malignant meningioma with spinal metastasis. Advanced treatment was refused, and
      the patient died. CONCLUSION: Spinal magnetic resonance imaging should be
      performed because of the high spinal metastatic rate, especially when spinal
      symptoms and signs are present. Immunohistochemical study has an important role
      in the differential diagnosis of primary or metastatic intracranial neoplasms.

PMID- 17172989
TI  - Ex vivo and in vitro determination of the axial rotational axis of the human
      thoracic spine.
AB  - STUDY DESIGN: Different geometrical and biomechanical evaluations were performed
      to determine the axial rotational axis of the thoracic spine. OBJECTIVE: Our
      research group has been dealing with the determination of the axial rotational
      axis of the thoracic spine. Here, we would like to present the geometrical and
      experimental results of our trials. With our experiments, we are trying to
      evaluate the contradictions of the related literature. SUMMARY OF BACKGROUND
      DATA: In the present state, we know quite a lot about the biomechanics of healthy
      and pathologic spines. Nevertheless, for a seemingly simple question like the
      position of the axial rotation of the thoracic spine, the literature gives
      contradicting results. During correction of a scoliotic deformity, when trying to
      correct the pathologic rotation, not knowing the physiologic rotation can be
      hazardous. METHODS: We wanted to clarify this question, so we examined the
      thoracic spine in many different ways. First, we examined the problem from a
      geometrical point of view then we modeled the different rotational axes by
      studying the change in volume of the spinal canal. Finally, we used cadaver
      spines that we rotated and examined with radiographs and digital pictures.
      RESULTS: Based on the results, we made the following establishments: most of the
      center points fell on the anterior half of the vertebral body or into the spinal
      canal, basically on the midsagittal axis of the vertebra. The rib cage has a
      significant effect on the place of the axis. After removing the ribs, the axis of
      axial rotation moved forward. CONCLUSIONS: After evaluating the results, we
      determined that the most likely place for the rotational axis is on the median
      sagittal plane, in the anterior portion of the spinal canal.

PMID- 17172990
TI  - Biomechanical rationale for using polyetheretherketone (PEEK) spacers for lumbar
      interbody fusion-A finite element study.
AB  - STUDY DESIGN: To determine the effect of cage/spacer stiffness on the stresses in
      the bone graft and cage subsidence. OBJECTIVE: To investigate the effect of cage
      stiffness on the biomechanics of the fused segment in the lumbar region using
      finite element analysis. SUMMARY OF BACKGROUND DATA: There are a wide variety of
      cage/spacer designs available for lumbar interbody fusion surgery. These range
      from circular, tapered, rectangular with and without curvature, and were
      initially manufactured using titanium alloy. Recent advances in the medical
      implant industry have resulted in using medical grade polyetheretherketone
      (PEEK). The biomechanical advantages of using different cage material in terms of
      stability, subsidence, and stresses in bone graft are not fully understood.
      METHODS: A previously validated 3-dimensional, nonlinear finite element model of
      an intact L3-L5 segment was modified to simulate posterior interbody fusion
      spacers made of PEEK ("E" = 3.6 GPa) and titanium ("E" = 110 GPa) at the L4/5
      disc with posterior instrumentation. Bone graft ("E" = 12 GPa) packed between the
      spacers in the intervertebral space was also simulated. The posterior lumbar
      interbody fusion spacer with instrumentation and graft represent a simulation of
      the condition present immediately after surgery. RESULTS: The peak centroidal Von
      Mises stresses in the graft bone increased by at least 9-fold with PEEK spacers
      as compared to titanium spacer. The peak centroidal Von Mises stresses in the
      endplates increased by at least 2.4-fold with titanium spacers over the PEEK
      spacers. These stresses were concentrated at places where the spacer interfaced
      with the endplate. The stiffness of the spacer did not affect the relative motion
      (stability) across the instrumented (L4/5) segment. CONCLUSIONS: Spacers less
      stiff than the graft will: (1) provide stability similar to titanium cages in the
      presence of posterior instrumentation, (2) reduce the stresses in endplates
      adjacent to the spacers, and (3) increase the load transfer through the graft, as
      evident from the increase in stresses in graft.

PMID- 17172991
TI  - Low back pain patients demonstrate increased hip extensor muscle activity during
      standardized submaximal rotation efforts.
AB  - STUDY DESIGN: A comparative study of trunk and hip extensor muscle recruitment
      patterns in 2 subject groups. OBJECTIVE: To examine for changes in recruitment of
      the hip and back extensor muscles during low level isometric trunk rotation
      efforts in chronic low back pain (CLBP) subjects by comparison with matched
      asymptomatic control subjects. SUMMARY OF BACKGROUND DATA: Anatomic and
      biomechanical models have provided evidence that muscles attaching to the
      thoracolumbar fascia (TLF) are important for providing stabilization to the
      lumbopelvic region during trunk rotation. This has guided rehabilitation
      programs. The muscles that link diagonally to the posterior layer of the TLF have
      not previously been examined individually and compared during low-level trunk
      rotation efforts in CLBP patients and matched controls. METHODS: Thirty CLBP
      patients and 30 matched controls were assessed using surface electromyography
      (EMG) as they performed low-level isometric rotation efforts while standing
      upright. Muscles studied included latissimus dorsi, erector spinae, upper and
      lower gluteus maximus, and biceps femoris. Subjects performed the rotation
      exertion with various levels of external trunk support, related to different
      functional tasks. RESULTS: EMG results demonstrated that subjects with CLBP had
      significantly higher levels of recruitment for the lower and upper gluteus
      maximus (P < 0.05), hamstrings (P < 0.05), and erector spinae muscles (P < 0.05)
      during rotation to the left compared with the control subjects. CONCLUSION: This
      study provided evidence of increased muscle recruitment in CLBP patients when
      performing a standardized trunk rotation task. These results may have
      implications for the design of therapeutic exercise programs for CLBP patients.

PMID- 17172993
TI  - Substance P-saporin down-regulates substance P receptor immunoreactive sensory
      dorsal root ganglion neurons innervating the lumbar intervertebral discs in rats.
AB  - STUDY DESIGN: To examine changes in substance P receptors on dorsal root ganglion
      cells innervating the rat lumbar intervertebral discs using immunohistochemistry
      and a retrograde neurotracing method. OBJECTIVE: We evaluated the effects of
      intradiscal administration of substance P-saporin, a toxin selective for cells
      expressing substance P receptors. SUMMARY OF BACKGROUND DATA: The rat L5/6
      intervertebral disc is multi-segmentally innervated from the L1-L6 dorsal root
      ganglions. Substance P and the neurokinin-1 receptor contribute to inflammatory
      pain transmission. Substance P immunoreactive-sensory nerve fibers in human
      intervertebral discs and immunoreactive-dorsal root ganglion neurons innervating
      rat intervertebral discs have been reported to be important in the transmission
      of discogenic low back pain. In the current study, we evaluated the effects of
      intradiscal administration of substance P-saporin, a toxin selective for cells
      expressing substance P receptor. METHODS: Sixteen rats were used (control group,
      n = 8; substance P-saporin group, n = 8). To detect dorsal root ganglion neurons
      innervating the L5/6 intervertebral disc, neurotracer (fluoro-gold crystals) was
      placed into the intervertebral disc. Seven days after fluoro-gold application,
      the L5/6 intervertebral disc was exposed and injected with 175 ng of sterile
      substance P-saporin (substance P-saporin group, n = 8). Fourteen days after the
      first operation, each dorsal root ganglion was harvested, sectioned, and
      processed for neurokinin-1 immunohistochemistry using rabbit antibody to
      neurokinin-1. The numbers of fluoro-gold labeled neurons, and fluoro-gold labeled
      and neurokinin-1 immunoreactive neurons were counted in both groups. RESULTS:
      Neurons innervating the L5/6 intervertebral discs, retrogradely labeled with
      fluoro-gold, were distributed throughout dorsal root ganglions from L1 to L6 in
      both groups. Of fluoro-gold labeled neurons, the proportion of neurokinin-1
      immunoreactive neurons was 35% in the control group. However, the proportion of
      neurokinin-1 immunoreactive neurons was 8% after administration of substance P
      saporin into the intervertebral discs (substance P-saporin group). Substance P
      saporin significantly decreased the ratio of neurokinin-1 immunoreactive neurons.
      CONCLUSION: Substance P-saporin decreased the ratio of neurokinin-1
      immunoreactive neurons innervating the disc related to discogenic low back pain.
      Substance P-saporin may be a useful tool to investigate the mechanism of
      discogenic low back pain.

PMID- 17172994
TI  - Effects of the Second National Acute Spinal Cord Injury Study of high-dose
      methylprednisolone therapy on acute cervical spinal cord injury-results in spinal
      injuries center.
AB  - STUDY DESIGN: Retrospective single-center study. OBJECTIVE: To evaluate the
      recovery of motor function and the early complications in patients with acute
      cervical spinal cord injury after receiving a high dose of methylprednisolone
      sodium succinate (MPSS) within 8 hours of injury. SUMMARY OF BACKGROUND DATA:
      High-dose MPSS therapy has been demonstrated to improve the neurologic recovery
      in patients with acute spinal cord injury. However, it remains a controversial
      treatment. METHODS: Seventy patients were included in this study: 37 in the MPSS
      group who were treated with MPSS within 8 hours of their injury according to the
      Second National Acute Spinal Cord Injury Study protocol, and 33 in non-MPSS group
      who were not administered with MPSS. Improvements in the American Spinal Injury
      Association motor score were compared between the MPSS group and the non-MPSS
      group. In patients with complete motor loss at admission and follow-up periods,
      improvements of myotomal levels between the MPSS (n = 15) and non-MPSS groups (n
      = 21) were compared. Early complications within 6 weeks of high-dose MPSS therapy
      were compared with those of no MPSS therapy. RESULTS: Among the patients with
      incomplete paralysis at admission, the American Spinal Injury Association motor
      scores in the MPSS group were improved more significantly than those in the non
      MPSS group at 6 weeks and 6 months after injury. Meanwhile, among the patients
      with complete paralysis at admission, the patients in the MPSS group did not show
      significantly more change in motor score than those in the non-MPSS group.
      Improvement in myotomal level had no significant difference between the MPSS and
      non-MPSS groups. The MPSS group had 10 patients with early complications, while
      the non-MPSS group had 14. The differences between the 2 groups showed no
      statistical significance. CONCLUSIONS: MPSS should be administered to patients
      with incomplete cervical spinal cord injury according to the Second National
      Acute Spinal Cord Injury Study protocol.

PMID- 17172996
TI  - Long-term results of expansive open-door laminoplasty for cervical myelopathy-
      average 14-year follow-up study.
AB  - STUDY DESIGN: Retrospective case series on long-term follow-up results of
      original expansive open-door laminoplasty for cervical myelopathy due to cervical
      spondylosis (CSM) and ossification of posterior longitudinal ligament (OPLL).
      OBJECTIVES: To elucidate efficacy and problems of original open-door laminoplasty
      to improve future surgical outcomes. SUMMARY OF BACKGROUND DATA: Little
      information is available on long-term outcomes of original open-door laminoplasty
      without grafts, implants, or instruments. METHOD: The study group included 80
      patients who underwent original open-door laminoplasty and were followed for
      minimum 10 years. Clinical results, including Japanese Orthopedic Association
      scores, recovery rates, occurrences of complications, and long-term deterioration
      were investigated. Cervical alignments, type of OPLL, cervical range of motion,
      anteroposterior diameter of spinal canal, and progression of OPLL were assessed
      on plain radiographs. Spinal cord decompression was verified on magnetic
      resonance imaging. RESULTS: Average Japanese Orthopedic Association score and
      recovery rate improved significantly until 3 years after surgery and remained at
      an acceptable level in both cervical spondylosis and OPLL patients with slight
      deterioration after 5 years. Segmental motor palsy developed in 8 patients. Late
      deterioration, mainly lower extremity motor score decline, developed in 8 CSM and
      16 OPLL patients. Overall cervical range of motion decreased by 36%. Patients
      with cervical lordosis decreased gradually in both patient groups. Such changes
      in alignments did not affect surgical results in CSM patients, while OPLL
      patients with preoperative kyphosis had lower recovery rates than those with
      straight and lordotic alignments. OPLL progression that was detected in 66% of
      patients did not affect clinical results. Although infrequent, magnetic resonance
      imaging revealed atrophy of spinal cord, spinal cord compression at adjacent
      segments due to degenerative changes and OPLL progression. CONCLUSIONS: Long-term
      results of open-door laminoplasty without bone graft, graft substitutes, or
      instruments were satisfactory. However, segmental motor paralysis, kyphosis,
      established before and after surgery, OPLL progression, and late deterioration
      due to age-related degeneration remain challenging problems.

PMID- 17172997
TI  - Thirty-six years experience of cervical extension osteotomy in ankylosing
      spondylitis: techniques and outcomes.
AB  - STUDY DESIGN: A retrospective review of the cervical extension osteotomy in the
      past 36 years for the treatment of flexion deformity of patients with ankylosing
      spondylitis was conducted. OBJECTIVES: To review the conventional and current
      surgical techniques of cervical extension osteotomy in ankylosing spondylitis and
      to evaluate the clinical outcomes. SUMMARY OF BACKGROUND DATA: Cervical osteotomy
      is a challenging procedure in the correction of flexion deformity in ankylosing
      spondylitis. Some authors prefer using general anesthesia and prone position for
      their surgery, and some, including the authors, use the sitting position.
      METHODS: A review of 131 cases of cervical spine osteotomy was carried out. The
      accumulation of 131 cases was classified into two phases: 114 cases from 1967 to
      1997 (conventional technique group) by our senior author and 17 cases from 1997
      to 2003 (current technique group) by our first author. Patient follow-up was
      obtained by a combination of retrospective chart review and telephone interview
      by 2 independent physicians. The flexion deformity was measured before surgery
      and after surgery using chin-brow to vertical angle. RESULTS: There were 114
      patients in the conventional group and 17 patients in the current group. The
      average preoperative and postoperative angle was 56 degrees and 4 degrees ,
      respectively, in the conventional group and 49 degrees and 12 degrees ,
      respectively, in the current group. CONCLUSIONS: The sitting position with local
      anesthesia is safe and allows for correction of deformity in a controlled manner.
      The increased lateral resection area reduces the possibility of nerve root
      impingement and provides ample room for the spinal cord. The cranial halo can
      also be adjusted after surgery to modify the head/neck position and can be
      adjusted to alleviate any C8 nerve root impingement. The procedure demands great
      attention to detail to minimize risk.

PMID- 17172998
TI  - Postoperative segmental C5 palsy after cervical laminoplasty may occur without
      intraoperative nerve injury: a prospective study with transcranial electric motor
      evoked potentials.
AB  - STUDY DESIGN: Intraoperative neurophysiologic monitoring with transcranial
      electric motor-evoked potentials was performed on patients who underwent cervical
      laminoplasty at a university hospital in a prospective study. OBJECTIVE: To
      evaluate the usefulness of intraoperative spinal cord monitoring with
      transcranial electric motor-evoked potentials for prediction of the occurrence of
      segmental motor paralysis after cervical laminoplasty. SUMMARY OF BACKGROUND
      DATA: Segmental motor paralysis occasionally occurs among patients who undergo
      expansive laminoplasty for cervical myelopathy, and it has been attributed to
      nerve root lesions caused by either a traumatic surgical technique or a tethering
      effect after decompression. METHODS: Sixty-two consecutive patients (47 men and
      15 women; mean age 64 years [range 32-89]) who were scheduled to undergo cervical
      laminoplasty under intraoperative spinal cord monitoring with transcranial
      electric motor-evoked potentials were included in this study. Transcranial
      electrical stimulations were delivered through pin-type electrodes, and the
      evoked potentials were recorded over the deltoid, biceps, and triceps muscles in
      the bilateral upper extremities and thoracic spinal cord. RESULTS: Intraoperative
      evoked potentials were successfully recorded in all muscles in 57 patients (92%),
      and incomplete evoked potentials were recorded in the remaining 5 patients. No
      critical decrease in the amplitude of the evoked potentials was observed in any
      of the 62 patients. All patients showed sufficient postoperative recovery from
      their clinical symptoms; however, postoperative transient C5 palsy occurred in 3
      patients. CONCLUSIONS: No abnormalities were observed on transcranial electric
      motor-evoked potential monitoring, even in those patients who developed
      postoperative transient C5 palsy. These results suggest that the development of
      postoperative C5 palsy after cervical laminoplasty is not associated with
      intraoperative injury of the nerve root or the spinal cord, although the precise
      mechanism of its development is still unclear. Surgeons should be aware that C5
      palsy is a possible complication of cervical laminoplasty, even in the absence of
      intraoperative nerve injury.

PMID- 17172999
TI  - Repeat surgical interventions following "definitive" instrumentation and fusion
      for idiopathic scoliosis.
AB  - STUDY DESIGN: A retrospective chart review was performed on all idiopathic
      scoliosis patients treated with instrumented spinal fusion over a 15-year period.
      OBJECTIVES: To provide an experience from a single institution over a prolonged
      time period. The goal was to determine the frequency of repeat surgical
      interventions following the "definitive" spinal fusion surgery and identify the
      factors responsible for these reoperations. SUMMARY OF BACKGROUND DATA:
      Instrumented spinal fusion remains the standard of care in the surgical
      management of idiopathic scoliosis. This surgery is considered a "definitive"
      procedure where, barring a complication, no additional surgical procedures are
      planned. Although many studies have reported the frequency of specific
      complications following spinal fusion, little information currently exists
      regarding the cumulative average of these repeat surgical interventions that
      occur following these "definitive" procedures. METHODS: Surgical logs were
      reviewed on all patients who had an instrumented spinal fusion for idiopathic
      scoliosis from January 1988 through December 2002. All subsequent surgical
      interventions on these patients were then identified from the logs through
      December 2004. Pertinent information was gleaned from surgical logs and patient
      charts to provide details for these reoperations. RESULTS: A total of 1,046
      patients underwent an instrumented spinal fusion for idiopathic scoliosis: 809
      had a posterior-only fusion, 228 had an anterior-only fusion, and 9 had a
      combined anterior/posterior spinal fusion. A total of 172 repeat surgical
      interventions were performed in 135 patients (12.9%). Of these 135 patients, 29
      patients (21.5%) had two or more separate procedures performed. The most common
      reasons for reoperation were infection, symptomatic implant, and pseudarthrosis.
      Patients who had posterior fusions had a significantly higher rate of reoperation
      than patients who had anterior fusions (14.0% vs. 9.3%). Reoperations due to
      infections and symptomatic implants occurred with significantly higher frequency
      in the posterior spine fusion group compared with those with anterior spinal
      fusion. No differences in rates of reoperation for pseudarthrosis were noted
      between posterior and anterior fusion groups. CONCLUSIONS: Repeat surgical
      interventions are relatively common following these supposedly definitive
      surgical procedures. The most common reasons for return to surgery are infection,
      symptomatic implant, and pseudarthrosis.

PMID- 17173000
TI  - A review of quality of life and psychosocial issues in scoliosis.
AB  - STUDY DESIGN: Recent literature regarding the psychological impact of scoliosis
      was reviewed. OBJECTIVE: To determine the impact of scoliosis on health-related
      quality of life (HRQL), psychosocial functioning, and body image to improve
      patient outcomes. SUMMARY OF BACKGROUND DATA: Adolescents and adults with
      adolescent idiopathic scoliosis have been known to score lower than healthy
      controls on HRQL measures. However, HRQL instruments may not adequately capture
      psychological distress experienced by patients. METHODS: Research papers
      concerning HRQL and psychosocial factors in patients with scoliosis were
      reviewed. RESULTS: Studies of psychosocial health and body image have revealed
      that functioning in these domains may affect compliance behavior and satisfaction
      with treatment outcomes among adolescent patients. Psychosocial and body image
      disturbance is less marked in patients with good social or family functioning, or
      patients who exercise regularly or are psychologically healthy. Adults with
      scoliosis generally display fewer psychological problems than adolescents.
      However, adults with scoliosis may experience psychosocial limitations due to
      poor physical health or body image disturbance. Support group membership can
      improve psychosocial health in adults with scoliosis. CONCLUSIONS: Adolescent
      patients with scoliosis may experience psychosocial difficulties, especially
      while undergoing treatment for scoliosis. Interventions aimed at managing
      psychosocial or body image disturbances may help to ameliorate the potentially
      negative impact of scoliosis on these facets of life.

PMID- 17173001
TI  - Comparison of Cobb angles in idiopathic scoliosis on standing radiographs and
      supine axially loaded MRI.
AB  - STUDY DESIGN: Prospective, patient controlled. OBJECTIVE: To compare Cobb angles
      in idiopathic scoliosis between standing radiographs and a nonradiographic
      procedure. SUMMARY OF BACKGROUND DATA: Repeated radiographic examinations at
      young age may increase the risk for breast cancer in adulthood. MRI images the
      spine satisfactorily but is cumbersome in standing. A harness supplying axial
      load to a lying subject simulates the standing radiograph appearance of the
      lumbar spine. METHODS: Thirty patients with idiopathic scoliosis greater than 20
      degrees performed a routine posteroanterior and lateral standing thoracolumbar
      spine radiograph and an MRI in supine position without and with axial loading.
      RESULTS: Mean Cobb angle for the major curve was 31 degrees on standing
      radiographs, 23 degrees on nonloaded supine MRI, and 31 degrees on supine loaded
      MRI. Axially loaded, compared with nonloaded, MRI increased the Cobb angle by 8
      degrees. The mean difference between standing radiograph and supine axially
      loaded MRI was 0 degrees, with an intermethodologic variation(s) of 3.4 degrees.
      Radiographic and MRI (axially loaded) Cobb angles correlated positively (r =
      0.78). CONCLUSIONS: Axial loading on supine MRI produces coronal Cobb angles
      similar to standing radiographs. This is a way to acquire reliable Cobb angles
      without radiation in the monitoring of idiopathic scoliosis.

PMID- 17173002
TI  - Low back pain in a general population. Natural course and influence of physical
      exercise--a 5-year follow-up of the Musculoskeletal Intervention Center-Norrtalje
      Study.
AB  - STUDY DESIGN: A 5-year prospective cohort study was conducted of men and women
      seeking care for a new period of low back pain (LBP). OBJECTIVES: To study the
      natural course of pain and disability due to LBP during a 5-year follow-up
      period, and to investigate the possible influence of regular physical exercise on
      recovery. SUMMARY OF BACKGROUND DATA: LBP is major health problem, but its
      natural course is not very well studied. Several studies have investigated the
      role of physical exercise on LBP disorders, with inconsistent results. METHODS:
      At baseline, a total of 790 subjects seeking care for LBP were interviewed about
      physical exercise during leisure time. Over 5 years, 3 follow-up assessments were
      made by postal questionnaire. At all measuring points, pain intensity ratings and
      disability scores were compared between men and women, and among 3 exercise
      categories. RESULTS: The pain intensity and disability scores were improved after
      5 years for both men and women. The most prominent improvements occurred after 6
      months, but less so thereafter. There were no significant differences between men
      and women with regard to individual changes at the 5-year follow-up concerning
      the pain intensity or disability scores. There were no significant differences,
      either for women or men, between low, median, or high intensity exercise groups
      regarding pain intensity or disability values for the individual change at the 5
      year follow-up. CONCLUSIONS: Over a 5-year period, both men and women who had
      sought care for LBP reported a decrease in pain and disability; however, only a
      few were fully restored. In this study, we found no effect of nonspecific
      physical exercise on recovery from LBP in men and women.

PMID- 17173003
TI  - Back pain exacerbations and lost productive time costs in United States workers.
AB  - STUDY DESIGN: Cross-sectional with follow-up case-control component. OBJECTIVES:
      To measure the prevalence of back pain (BP) and back pain exacerbations, describe
      BP features and functional impairment, estimate BP-related lost productive time
      (LPT) and costs, and assess the relation between pain exacerbations and lost
      productive time. SUMMARY OF BACKGROUND DATA: BP is associated with substantial
      lost work time. However, little is known about the extent to which BP with or
      without exacerbation explains lost work time. METHODS: A national telephone
      survey of the U.S. workforce identified 320 workers 40 to 65 years of age with BP
      defined by NHANES I criteria and 91 matched non-BP controls. Participants self
      reported pain characteristics, lost productive time (absenteeism and
      presenteeism) in the previous 2 weeks, activity limitations, and demographics. A
      population-weighting adjustment was applied to estimates to account for selection
      bias and ensure that estimates of certain sample demographic subgroups' totals
      conformed to the Current Population Survey. RESULTS: The 2-week period prevalence
      of BP was 15.1%; 42% of workers with BP experienced pain exacerbations. BP
      prevalence was associated with demographic factors, but BP exacerbations were
      not. BP was reported by 42.6% of all workers. Workers with exacerbations reported
      more days with BP than those without exacerbations. Workers with exacerbations
      were significantly more likely than those without such exacerbations to report
      activity limitation (88.4% vs. 60.7%; P < 0.0001) and BP-related LPT (22.1% vs.
      13.0%; P = 0.0259). BP in workers 40 to 65 years of age costs employers an
      estimated $7.4 billion/year. Workers with BP exacerbations account for 71.6% of
      this cost. CONCLUSIONS: Workers with BP exacerbations account for a
      disproportionate share of the cost of BP-related lost productive time.

PMID- 17173004
TI  - The impact of disability compensation on long-term treatment outcomes of patients
      with sciatica due to a lumbar disc herniation.
AB  - STUDY DESIGN: Prospective, observational study. OBJECTIVE: To compare long-term
      disability and health-related quality of life outcomes of individuals receiving
      or not receiving workers' compensation at baseline evaluation. SUMMARY OF
      BACKGROUND DATA: Disability compensation has long been associated with poor
      clinical outcomes. However, most studies have assessed outcomes over short time
      periods using unvalidated measures without controlling for potential confounders.
      METHOD: Patients with sciatica due to a herniated lumbar disc were treated by
      physicians in community based orthopedic, neurosurgical, and occupational
      medicine practices throughout Maine. Outcomes assessed included disability
      compensation and work status, and health-related quality of life, controlling for
      initial treatment received and factors predicting initial workers' compensation
      status. RESULTS: Among 440 eligible patients, 172 (86%) receiving workers'
      compensation and 222 (92%) not receiving workers' compensation at baseline
      evaluation completed at least one follow-up between 5 and 10 years (80% completed
      10-year). Baseline demographics, past back history, imaging findings, symptoms,
      functional status, and expectations significantly differed according to the
      patient's baseline workers' compensation status. After 5-10 years, most patients,
      regardless of baseline workers' compensation status (yes or no), were not
      receiving disability compensation (83% vs. 96%, respectively) and were employed
      (78% for both groups). However, workers' compensation patients were significantly
      more likely to be receiving disability compensation and had worse symptoms,
      functional status, and satisfaction outcomes. Outcome differences diminished in
      magnitude after controlling for baseline differences among patients receiving
      workers' compensation or not but continued to favor those not initially receiving
      workers' compensation. Initial treatment received, either surgical or
      nonsurgical, did not influence these findings. CONCLUSIONS: Long-term employment
      and disability outcomes were favorable for most patients with a disc herniation,
      regardless of initial workers' compensation status. However, individuals
      initially receiving workers' compensation had worse disability and quality of
      life outcomes compared to individuals not receiving workers' compensation.
      Despite these differences, long-term work outcomes were similarly favorable.

PMID- 17173005
TI  - The International Society for the Study of the Lumbar Spine: research trends over
      time and publication rates.
AB  - STUDY DESIGN AND OBJECTIVES: A retrospective review was conducted to assess
      trends in research selected for podium presentation at ISSLS. SUMMARY OF
      BACKGROUND DATA: Abstracts of past papers presented to ISSLS provide quantified
      documentation of trends in research as well as insight into future directions.
      METHODS: A systematic review of abstracts of research presented was performed.
      Graphical plots in each category of research and aspects of study quality were
      used to identify any trends. Univariate and multivariate logistical regression
      analyses were used to identify factors related to eventual publication. RESULTS:
      A total of 43% of selected papers focused on the disc, representing the single
      largest area of research. There is a linear trend over time toward increased
      selection of basic science papers and decreased clinical papers. Experimental
      research design is becoming more frequently selected. In 1978, over 80% of papers
      were purely descriptive. By 2002, 42% of papers were descriptive, whereas 40%
      incorporated an experimental design. However, over the past decade, there has
      been a linear increase in the proportion of randomized controlled trials among
      clinical papers compared with basic science or biomechanical papers. A total of
      54% of all abstracts presented recently went on to publication. Independent
      factors that were associated with significantly (P < 0.05) higher publication
      rates included use of blinded or independent observers (84.6%), experimental
      design (68.4%), basic science or biomechanical papers (62.3%), and statistically
      positive result (61.8%). CONCLUSION: Overall, the type of research selected for
      presentation at ISSLS has improved over the years in regards to greater use of
      experimental and randomized study design. The eventual publication rates compare
      favorably to other research societies. Factors related to publication have been
      identified and should be considered in future research.

PMID- 17173006
TI  - Measurement of the local pressure of the intervertebral foramen and the
      electrophysiologic values of the spinal nerve roots in the vertebral foramen.
AB  - STUDY DESIGN: The intraoperative findings of the local pressure of the
      intervertebral foramen and the electrophysiologic values of the spinal nerve
      roots were evaluated. OBJECTIVE: To investigate the neurophysiologic changes of
      the spinal nerve roots in the vertebral foramen. SUMMARY OF BACKGROUND DATA: As
      far as we know, few reports have so far described the neurophysiologic changes of
      the spinal nerve roots in the vertebral foramen. METHODS: The local pressure of
      the intervertebral foramen was continuously measured while the lumbar spine
      posture was changed in 66 vertebral foramens. In addition, 20 L5 nerve roots were
      electrophysiologically evaluated using the compound muscle action potentials
      (CMAPs) from tibialis anterior (TA) muscle after L5 nerve root stimulation.
      RESULTS: The local pressure of the intervertebral foramen was significantly
      increased during lumbar spine extension (P < 0.001); moreover, the latency and
      amplitude of the CMAPs both significantly deteriorated in line with the
      increasing local pressure. CONCLUSIONS: Our findings suggested that a double
      compression of the nerve root exists in lumbar spinal stenosis with lumbar spine
      extension, which includes the spinal canal and the vertebral foramen.

PMID- 17173007
TI  - Ocular haemodynamics in pseudoexfoliative and primary open-angle glaucoma.
AB  - OBJECTIVE: To compare the retrobulbar haemodynamic parameters in the ophthalmic
      artery (OA) and short posterior ciliary arteries (SPCA) in pseudoexfoliative and
      primary open-angle glaucoma patients. SUBJECTS AND METHODS: Fourty-three eyes
      from 43 patients with pseudoexfoliative glaucoma (PXE) and 31 eyes from 31
      patients with primary open-angle glaucoma (POAG) who met the inclusion/exclusion
      criteria were included in this prospective cross-sectional study. Colour Doppler
      imaging measurements, peak systolic velocity (PSV), and end-diastolic velocity
      (EDV) were assessed in the OA and posterior ciliary arteries (PCA). Pourcelot
      resistivity indices (RI) were calculated. Visual function was assessed using the
      24-2 Swedish Interactive Threshold Algorithm (SITA). The main outcomes of the
      study were PSV, EDV, and RI in the OA and SPCA. RESULTS: In POAG patients, PSV
      and EDV were significantly lower in the OA, P=0.003 and P<0.001 respectively, and
      in the PCA, P=0.003 and P<0.001 respectively, when compared with the PXE group.
      The RI was significantly higher, P<0.001, in both vessels, in the POAG group.
      CONCLUSION: The results of this study have found reduced PSV and EDV and
      increased RI in the retrobulbar vessels of POAG patients when compared with PXE
      patients.

PMID- 17173008
TI  - A survey of measures used for the prevention of postoperative endophthalmitis
      after cataract surgery in the United Kingdom.
AB  - PURPOSE: This study investigates the current practice of United Kingdom (UK)
      ophthalmologists in perioperative antibiotic and antiseptic use in cataract
      surgery. MATERIALS AND METHODS: A telephone interview survey was conducted with
      ophthalmic staff at all ophthalmic training units in the UK in October and
      November 2005. RESULTS: The practices of a total of 800 consultants were
      ascertained. Preoperatively, 795 (99.4%) surgeons used povidone-iodine to prepare
      the skin. In all, 558 (69.8%) instilled 5 or 10% povidone-iodine in the
      conjunctival sac; 47 (5.9%) gave preoperative antibiotic eyedrops.
      Intraoperatively, intracameral antibiotics were given either as a bolus [80
      (10.0%) intracameral cefuroxime, 29 (3.6%) intracameral vancomycin] or in the
      irrigating fluid [33 (4.1%) vancomycin]. 48 (6.0%) gave subconjunctival
      gentamycin only routinely, 531 (66.4%) gave subconjunctival cefuroxime, and 39
      (4.9%) gave other subconjunctival antibiotics. A single dose of topical
      antibiotics was given by 134 (16.8%) surgeons. Postoperatively, 515 (64.4%) used
      a combination steroid and neomycin eyedrop, and 213 (26.6%) gave a separate
      steroid and chloramphenicol eyedrop. CONCLUSIONS: This study reveals wide
      variations in the choice and duration of antibiotics used by UK ophthalmologists.
      The predominant methods of intraoperative prophylaxis are subconjunctival
      cefuroxime and intracameral cefuroxime. Most surgeons used a neomycin eyedrop for
      postoperative prophylaxis.

PMID- 17173009
TI  - Sodium hyaluronate eye drops prevent late-onset bleb leakage after trabeculectomy
      with mitomycin C.
AB  - PURPOSE: To evaluate the efficacy of sodium hyaluronate eye drops for prevention
      of late-onset bleb leakage after trabeculectomy with mitomycin C (MMC). METHODS:
      Sixty-eight patients (68 eyes) who had trabeculectomy with MMC from March 1995 to
      February 2002 at the Marui Eye Clinic or the Department of Ophthalmology,
      Fukushima Medical University Hospital were examined in this study. Twenty-two
      were treated postoperatively with sodium hyaluronate eye drops (sodium
      hyaluronate group) and 46 eyes were not treated postoperatively (control group).
      The blebs were classified according to the avascular area, epithelial defect and
      degree of bleb wall leakage. Both groups were assigned classes (0, avascular or
      partial avascular bleb; 1, avascular or partial avascular bleb with an epithelial
      defect; 2, avascular or partial avascular bleb with oozing; 3, avascular or
      partial avascular bleb with a point of leakage). RESULTS: Follow-up duration
      ranged from 10 to 116 months (mean+/-SD, 57.6+/-30.5). The incidence of
      reclassification from class 1 to class 0 was significantly greater in the sodium
      hyaluronate group (four of six class 1 eyes improved to class 0 after application
      of sodium hyaluronate eye drops) than in the control group (zero of 10 eyes)
      (P=0.008). And, the incidence of reclassification from class 1 to class 2 or
      class 3 was significantly smaller in the sodium hyaluronate group (one of six
      eyes) than in the control group (nine of 10 eyes) (P=0.008). CONCLUSIONS: Sodium
      hyaluronate eye drops may prevent late-onset bleb leakage after trabeculectomy
      with MMC.

PMID- 17173010
TI  - Peripapillary choroidal neovascularization in Bietti crystalline retinopathy.

PMID- 17173011
TI  - Familial central retinal vein occlusion.
AB  - AIM: To report four cases of central retinal vein occlusion (CRVO) in a French
      family. PATIENTS AND METHODS: Ophthalmological examination and medical work-up of
      seven members of the family. RESULTS: There were four cases of CRVO in two
      consecutive generations. Three of them had CRVO in both eyes. Arterial
      hypertension was present in two, associated to glaucoma in one. Medical work-up
      did not reveal additional risk factors. CONCLUSIONS: We report a case of familial
      clustering of CRVO. Our cases combined to other cases reported in the literature
      provide arguments for the existence in some subjects of a genetic predisposition
      of CRVO. Additional case series are however needed to confirm this hypothesis.

PMID- 17173012
TI  - Localised abscess following an injection of subtenon triamcinolone acitonide.

PMID- 17173013
TI  - Evaluation of peripapillary detachment in pathologic myopia with en face optical
      coherence tomography.
AB  - BACKGROUND: A newly recognized lesion in pathologic myopia is peripapillary
      detachment of the retinal pigment epithelium (RPE) and retina. Recently
      introduced en face optical coherence tomography (OCT) provides not only cross
      sectional but also coronal scans of the retina, and allows lateral extent
      visualization and thickness measurement of lesions. METHODS: Three patients
      presenting bilateral peripapillary yellow-orange lobulated area in high myopia
      have been evaluated with fluorescein angiography (FA), indocyanine green
      angiography (ICGA), en face OCT (OCT/SLO; Ophthalmic Technologies Inc, Toronto,
      Canada), and Humphrey visual field analyzer. RESULTS: In all eyes, en face OCT
      has shown the presence of a peripapillary sub-RPE nonreflective area. The lateral
      extent of this area was clearly detectable and the measurement of its thickness
      was obtained. We detected a cleft in the RPE at one edge of the cavitation in two
      eyes, vascular tractions and vitreoretinal tractions in two eyes, a macular hole
      with posterior retinal detachment, and small areas of RPE detachment nonconnected
      with the peripapillary detachment in one eye. In the four eyes presenting a
      proper central fixation, glaucomatous visual field defects were evident.
      CONCLUSION: En face OCT has allowed to evaluate the thickness and the lateral
      extent of the peripapillary detachment. Therefore, its use could be important in
      determining the size and grading of these lesions at first visit, and to detect
      minimal changes of width and thickness during follow-up as an alternative to
      fluorescein angiography.

PMID- 17173014
TI  - Compressive optic neuropathy in fungal hypertrophic cranial pachymeningitis.

PMID- 17173016
TI  - A windfall for RNA.

PMID- 17173017
TI  - Chemical crosshairs on the central dogma.
AB  - As cellular machines and processes that regulate the flow of genomic information
      have come into sharper focus, a new level of chemical control has become
      possible. The scope of such chemical intervention extends from the mechanistic
      dissection of biochemical processes in living cells to the targeted control of
      gene networks and cell fate.

PMID- 17173018
TI  - RNA learns from antisense.
AB  - RNA interference provides powerful tools for controlling gene expression in
      cultured cells. Whether RNAi will provide similarly powerful drugs is unknown.
      Lessons from development of antisense oligonucleotide drugs may provide some
      clues.

PMID- 17173019
TI  - RNA at santa cruz.
AB  - Nestled in an atmosphere that resembles a national park, the Center for Molecular
      Biology of RNA at the University of California, Santa Cruz is fulfilling Harry
      Noller's vision of bringing together multidisciplinary researchers to solve
      problems that range from finding obscure RNAs to understanding the origin of
      life.

PMID- 17173020
TI  - Fighting toxic copper in a bacterial pathogen.

PMID- 17173021
TI  - 'Turning on' riboswitches to their antibacterial potential.

PMID- 17173022
TI  - Shining a light on protein expression in living organisms.

PMID- 17173023
TI  - Are we there yet?

PMID- 17173024
TI  - Sensing RNA virus infections.

PMID- 17173026
TI  - Synthetic RNA circuits.
AB  - Natural and engineered RNA 'parts' can perform a variety of functions, including
      hybridizing to targets, binding ligands and undergoing programmed conformational
      changes, and catalyzing reactions. These RNA parts can in turn be assembled into
      synthetic genetic circuits that regulate gene expression by acting either in cis
      or in trans on mRNAs. As more parts are discovered and engineered, it should be
      increasingly possible to create synthetic RNA circuits that are able to carry out
      complex logical operations in cells, either superimposed on or autonomous to
      extant gene regulation.

PMID- 17173027
TI  - Natural expansion of the genetic code.
AB  - At the time of its discovery four decades ago, the genetic code was viewed as the
      result of a "frozen accident." Our current knowledge of the translation process
      and of the detailed structure of its components highlights the roles of RNA
      structure (in mRNA and tRNA), RNA modification (in tRNA), and aminoacyl-tRNA
      synthetase diversity in the evolution of the genetic code. The diverse assortment
      of codon reassignments present in subcellular organelles and organisms of
      distinct lineages has 'thawed' the concept of a universal immutable code; it may
      not be accidental that out of more than 140 amino acids found in natural
      proteins, only two (selenocysteine and pyrrolysine) are known to have been added
      to the standard 20-member amino acid alphabet. The existence of phosphoseryl-tRNA
      (in the form of tRNACys and tRNASec) may presage the discovery of other
      cotranslationally inserted modified amino acids.

PMID- 17173028
TI  - Slicer and the argonautes.
AB  - Though they started out as somewhat mysterious components of the RNAi effector
      complexes, Argonaute proteins have since taken center stage in RNAi gene
      silencing. They interact with small RNAs to effect gene silencing in all RNAi
      related pathways known so far. We will review the dramatic advances in our
      understanding of the role of the Argonautes in RNAi through studies of their
      structure and function.

PMID- 17173029
TI  - A critical ligamentous mechanism in the evolution of avian flight.
AB  - Despite recent advances in aerodynamic, neuromuscular and kinematic aspects of
      avian flight and dozens of relevant fossil discoveries, the origin of aerial
      locomotion and the transition from limbs to wings continue to be debated.
      Interpreting this transition depends on understanding the mechanical interplay of
      forces in living birds, particularly at the shoulder where most wing motion takes
      place. Shoulder function depends on a balance of forces from muscles, ligaments
      and articular cartilages, as well as inertial, gravitational and aerodynamic
      loads on the wing. Here we show that the force balance system of the shoulder
      evolved from a primarily muscular mechanism to one in which the acrocoracohumeral
      ligament has a critical role. Features of the shoulder of Mesozoic birds and
      closely related theropod dinosaurs indicate that the evolution of flight preceded
      the acquisition of the ligament-based force balance system and that some basal
      birds are intermediate in shoulder morphology.

PMID- 17173030
TI  - Exchange bias using a spin glass.
AB  - Exchange bias is commonly manifested as the hysteresis-loop shift observed when a
      ferromagnet is in contact with an antiferromagnet. Here, we report observations
      of exchange bias with unusual features of a ferromagnet in contact with a spin
      glass, demonstrating that this is a phenomenon of greater generality. The easily
      measured properties of the ferromagnet allow access to the internal magnetic
      degrees of freedom of the glass to which they are coupled. Our results show that
      a Co/CuMn bilayer system exhibits all the rich phenomena of coercivity
      enhancement, bias-field shifts and training effects associated with a
      conventional ferromagnet/antiferromagnet system. Nevertheless, striking
      differences arise, such as an orientation reversal of the bias field in a small
      temperature range just below the blocking temperature. We argue that all features
      can be understood within the context of a random-field model for long-ranged
      oscillatory Ruderman-Kittel-Kasuya-Yosida (RKKY) coupled spins.

PMID- 17173031
TI  - Unit-cell scale mapping of ferroelectricity and tetragonality in epitaxial
      ultrathin ferroelectric films.
AB  - Typically, polarization and strain in ferroelectric materials are coupled,
      leading to the generally accepted direct relation between polarization and unit
      cell tetragonality. Here, by means of high-resolution transmission electron
      microscopy we map, on the unit-cell scale, the degree of tetragonality and the
      displacements of cations away from the centrosymmetry positions in an ultrathin
      epitaxial PbZr(0.2)Ti(0.8)O(3) film on a SrRuO(3) electrode layer deposited on a
      SrTiO(3) substrate. The lattice is highly tetragonal at the centre of the film,
      whereas it shows reduced tetragonality close to the interfaces. Most strikingly,
      we find that the maximum off-centre displacements for the central area of the
      film do not scale with the tetragonality. This challenges the fundamental belief
      in a strong polarization-tetragonality coupling in PbTiO(3)-based ferroelectrics,
      at such thicknesses. Furthermore, a systematic reduction of the atomic
      displacements is measured at the interfaces, suggesting that interface-induced
      suppression of the ferroelectric polarization plays a critical role in the size
      effect of nanoscale ferroelectrics.

PMID- 17173032
TI  - The role of vacancies and local distortions in the design of new phase-change
      materials.
AB  - Phase-change materials are of tremendous technological importance ranging from
      optical data storage to electronic memories. Despite this interest, many
      fundamental properties of phase-change materials, such as the role of vacancies,
      remain poorly understood. 'GeSbTe'-based phase-change materials contain vacancy
      concentrations around 10% in their metastable crystalline structure. By using
      density-functional theory, the origin of these vacancies has been clarified and
      we show that the most stable crystalline phases with rocksalt-like structures are
      characterized by large vacancy concentrations and local distortions. The ease by
      which vacancies are formed is explained by the need to annihilate energetically
      unfavourable antibonding Ge-Te and Sb-Te interactions in the highest occupied
      bands. Understanding how the interplay between vacancies and local distortions
      lowers the total energy helps to design novel phase-change materials as evidenced
      by new experimental data.

PMID- 17173033
TI  - Controlled insulator-to-metal transformation in printable polymer composites with
      nanometal clusters.
AB  - Although organic semiconductors have received the most attention, the development
      of compatible passive elements, such as interconnects and electrodes, is also
      central to plastic electronics. For this, ligand-protected metal-cluster films
      have been shown to anneal at low temperatures below 250 degrees C to highly
      conductive metal films, but they suffer from cracking and inadequate substrate
      adhesion. Here, we report printable metal-cluster-polymer nanocomposites that
      anneal to a controlled-percolation nanostructure without complete sintering of
      the metal clusters. This overcomes the previous challenges while still retaining
      the desired low transformation temperatures. Highly water- and alcohol-soluble
      gold clusters (75 mg ml-1) were synthesized and homogeneously dispersed into
      poly(3,4-ethylenedioxythiophene) to give a material with annealed d.c.
      conductivity tuneable between 10(-4) and 10(5) S cm-1. These composites can
      inject holes efficiently into all-printed polymer organic transistors. The
      insulator-metal transformation can also be electrically induced at 1 MV cm-1,
      suggesting possible memory applications.

PMID- 17173034
TI  - High-performance elastomeric nanocomposites via solvent-exchange processing.
AB  - The incorporation of nanoparticles into engineering thermoplastics affords
      engineers an opportunity to synthesize polymer nanocomposites that potentially
      rival the most advanced materials in nature. Development of these materials is
      difficult because thermodynamic and kinetic barriers inhibit the dispersal of
      inorganic, often hydrophilic nanoparticles in hydrophobic polymer matrices. Using
      a new solvent-exchange approach, we preferentially reinforce the hard
      microdomains of thermoplastic elastomers with smectic clay of similar
      characteristic dimensions. The strong adhesion between the clay and the hard
      microdomains coupled with the formation of a percolative network not only
      stiffens and toughens, but increases the heat distortion temperature of the
      material and induces reversible thermotropic liquid-crystalline transitions. The
      discotic clay platelets induce morphological ordering over a range of length
      scales, which results in significant thermomechanical enhancement and expands
      high-temperature applications. Merging block-copolymer processing techniques with
      this method for preferential ordering of nanoparticle facilitates the development
      of new, hierarchically ordered materials.

PMID- 17173035
TI  - Molecular evolution of antibody cross-reactivity for two subtypes of type A
      botulinum neurotoxin.
AB  - Broadening antibody specificity without compromising affinity should facilitate
      detection and neutralization of toxin and viral subtypes. We used yeast display
      and a co-selection strategy to increase cross-reactivity of a single chain (sc)
      Fv antibody to botulinum neurotoxin type A (BoNT/A). Starting with a scFv that
      binds the BoNT/A1 subtype with high affinity (136 pM) and the BoNT/A2 subtype
      with low affinity (109 nM), we increased its affinity for BoNT/A2 1,250-fold, to
      87 pM, while maintaining high-affinity binding to BoNT/A1 (115 pM). To find the
      molecular basis for improved cross-reactivity, we determined the X-ray co-crystal
      structures of wild-type and cross-reactive antibodies complexed to BoNT/A1 at
      resolutions up to 2.6 A, and measured the thermodynamic contribution of BoNT/A1
      and A2 amino acids to wild-type and cross-reactive antibody binding. The results
      show how an antibody can be engineered to bind two different antigens despite
      structural differences in the antigen-antibody interface and may provide a
      general strategy for tuning antibody specificity and cross-reactivity.

PMID- 17173036
TI  - Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery.
AB  - Shigella use a special mechanism to invade epithelial cells called 'the trigger
      mechanism of entry', which allows epithelial cells to trap several bacteria
      simultaneously. On contact, Shigella deliver effectors into epithelial cells
      through the type III secretion system. Here, we show that one of the effectors,
      IpgB1, has a pivotal role in producing membrane ruffles by exploiting the RhoG
      ELMO-Dock180 pathway to stimulate Rac1 activity. Using pulldown assays, we
      identified engulfment and cell motility (ELMO) protein as the IpgB1 binding
      partner. IpgB1 colocalized with ELMO and Dock180 in membrane ruffles induced by
      Shigella. Shigella invasiveness and IpgB1-induced ruffles were less in ELMO- and
      Dock180-knockdown cells compared with wild-type cells. Membrane association of
      ELMO-Dock180 with ruffles were promoted when cells expressed an IpgB1-ELMO
      chimera, establishing that IpgB1 mimics the role of RhoG in producing membrane
      ruffles. Taken together, our findings show that IpgB1 mimicry is the key to
      invasion by Shigella.

PMID- 17173037
TI  - Dynein is required for receptor sorting and the morphogenesis of early endosomes.
AB  - The early endosome is organised into domains to ensure the separation of cargo.
      Activated mitogenic receptors, such as epidermal growth factor (EGF) receptor,
      are concentrated into vacuoles enriched for the small GTPase Rab5, which
      progressively exclude nutrient receptors, such as transferrin receptor, into
      neighbouring tubules. These vacuoles become enlarged, increase their content of
      intralumenal vesicles as EGF receptor is sorted from the limiting membrane, and
      eventually mature to late endosomes. Maturation is governed by the loss of Rab5
      and is accompanied by the movement of endosomes along microtubules towards the
      cell centre. Here, we show that EGF relocates to the cell centre in a dynein
      dependent fashion, concomitant with the sorting away of transferrin receptor,
      although it remains in Rab5-positive early endosomes. When dynein function is
      acutely disrupted, efficient recycling of transferrin from EGF-containing
      endosomes is retarded, loss of Rab5 is slowed and endosome enlargement is
      reduced.

PMID- 17173038
TI  - Reducing mitochondrial fission results in increased life span and fitness of two
      fungal ageing models.
AB  - Ageing of biological systems is accompanied by alterations in mitochondrial
      morphology, including a transformation from networks and filaments to punctuate
      units. The significance of these alterations with regard to ageing is not known.
      Here, we demonstrate that the dynamin-related protein 1 (Dnm1p), a mitochondrial
      fission protein conserved from yeast to humans, affects ageing in the two model
      systems we studied, Podospora anserina and Saccharomyces cerevisiae. Deletion of
      the Dnm1 gene delays the transformation of filamentous to punctuate mitochondria
      and retards ageing without impairing fitness and fertility typically observed in
      long-lived mutants. Our data further suggest that reduced mitochondrial fission
      extends life span by increasing cellular resistance to the induction of apoptosis
      and links mitochondrial dynamics, apoptosis and life-span control.

PMID- 17173039
TI  - Cdk and APC activities limit the spindle-stabilizing function of Fin1 to
      anaphase.
AB  - The fidelity of chromosome segregation depends on proper regulation of mitotic
      spindle behaviour. In anaphase, spindle stability is promoted by the
      dephosphorylation of cyclin-dependent kinase (Cdk) substrates, which results from
      Cdk inactivation and phosphatase activation. Few of the critical Cdk targets have
      been identified. Here, we identify the budding-yeast protein Fin1 (ref. 7) as a
      spindle-stabilizing protein whose activity is strictly limited to anaphase by
      changes in its phosphorylation state and rate of degradation. Phosphorylation of
      Fin1 from S phase to metaphase, by the cyclin-dependent kinase Clb5-Cdk1,
      inhibits Fin1 association with the spindle. In anaphase, when Clb5-Cdk1 is
      inactivated, Fin1 is dephosphorylated by the phosphatase Cdc14. Fin1
      dephosphorylation targets it to the poles and microtubules of the elongating
      spindle, where it contributes to spindle integrity. A non-phosphorylatable Fin1
      mutant localizes to the spindle before anaphase and impairs efficient chromosome
      segregation. As cells complete mitosis and disassemble the spindle, the ubiqutin
      ligase APC(Cdh1) targets Fin1 for destruction. Our studies illustrate how
      phosphorylation-dependent changes in the behaviour of Cdk1 substrates influence
      complex mitotic processes.

PMID- 17173040
TI  - PI(3)Kgamma has an important context-dependent role in neutrophil chemokinesis.
AB  - The directional movement of cells in a gradient of external stimulus is termed
      chemotaxis and is important in many aspects of development and differentiated
      cell function. Phophoinositide 3-kinases (PI(3)Ks) are thought to have critical
      roles within the gradient-sensing machinery of a variety of highly motile cells,
      such as mammalian phagocytes, allowing these cells to respond quickly and
      efficiently to shallow gradients of soluble stimuli. Our analysis of mammalian
      neutrophil migration towards ligands such as fMLP shows that, although
      PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3) accumulate in a PI(3)Kgamma-dependent
      fashion at the up-gradient leading-edge, this signal is not required for
      efficient gradient-sensing and gradient-biased movement. PI(3)Kgamma activity is
      however, a critical determinant of the proportion of cells that can move, that
      is, respond chemokinetically, in reaction to fMLP. Furthermore, this dependence
      of chemokinesis on PI(3)Kgamma activity is context dependent, both with respect
      to the state of priming of the neutrophils and the type of surface on which they
      are migrating. We propose this effect of PI(3)Kgamma is through roles in the
      regulation of some aspects of neutrophil polarization that are relevant to
      movement, such as integrin-based adhesion and the accumulation of polymerized (F)
      actin at the leading-edge.

PMID- 17173041
TI  - Functional interaction between PML and SATB1 regulates chromatin-loop
      architecture and transcription of the MHC class I locus.
AB  - The function of the subnuclear structure the promyelocytic leukaemia (PML) body
      is unclear largely because of the functional heterogeneity of its constituents.
      Here, we provide the evidence for a direct link between PML, higher-order
      chromatin organization and gene regulation. We show that PML physically and
      functionally interacts with the matrix attachment region (MAR)-binding protein,
      special AT-rich sequence binding protein 1 (SATB1) to organize the major
      histocompatibility complex (MHC) class I locus into distinct higher-order
      chromatin-loop structures. Interferon gamma (IFNgamma) treatment and silencing of
      either SATB1 or PML dynamically alter chromatin architecture, thus affecting the
      expression profile of a subset of MHC class I genes. Our studies identify PML and
      SATB1 as a regulatory complex that governs transcription by orchestrating dynamic
      chromatin-loop architecture.

PMID- 17173043
TI  - Coordinated memory replay in the visual cortex and hippocampus during sleep.
AB  - Sleep replay of awake experience in the cortex and hippocampus has been proposed
      to be involved in memory consolidation. However, whether temporally structured
      replay occurs in the cortex and whether the replay events in the two areas are
      related are unknown. Here we studied multicell spiking patterns in both the
      visual cortex and hippocampus during slow-wave sleep in rats. We found that
      spiking patterns not only in the cortex but also in the hippocampus were
      organized into frames, defined as periods of stepwise increase in neuronal
      population activity. The multicell firing sequences evoked by awake experience
      were replayed during these frames in both regions. Furthermore, replay events in
      the sensory cortex and hippocampus were coordinated to reflect the same
      experience. These results imply simultaneous reactivation of coherent memory
      traces in the cortex and hippocampus during sleep that may contribute to or
      reflect the result of the memory consolidation process.

PMID- 17173042
TI  - Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1.
AB  - Proper neutrophil migration into inflammatory sites ensures host defense without
      tissue damage. Phosphoinositide 3-kinase (PI(3)K) and its lipid product
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) regulate cell
      migration, but the role of PtdIns(3,4,5)P(3)-degrading enzymes in this process is
      poorly understood. Here, we show that Src homology 2 (SH2) domain-containing
      inositol-5-phosphatase 1 (SHIP1), a PtdIns(3,4,5)P(3) phosphatase, is a key
      regulator of neutrophil migration. Genetic inactivation of SHIP1 led to severe
      defects in neutrophil polarization and motility. In contrast, loss of the
      PtdIns(3,4,5)P(3) phosphatase PTEN had no impact on neutrophil chemotaxis. To
      study PtdIns(3,4,5)P(3) metabolism in living primary cells, we generated a novel
      transgenic mouse (AktPH-GFP Tg) expressing a bioprobe for PtdIns(3,4,5)P(3.) Time
      lapse footage showed rapid, localized binding of AktPH-GFP to the leading edge
      membrane of chemotaxing ship1(+/+)AktPH-GFP Tg neutrophils, but only diffuse
      localization in ship1(-/-)AktPH-GFP Tg neutrophils. By directing where
      PtdIns(3,4,5)P(3) accumulates, SHIP1 governs the formation of the leading edge
      and polarization required for chemotaxis.

PMID- 17173044
TI  - Effects of task demands on the responses of color-selective neurons in the
      inferior temporal cortex.
AB  - Categorization and fine discrimination are two different functions in visual
      perception, and we can switch between these two functions depending on the
      situation or task demands. To explore how visual cortical neurons behave in such
      situations, we recorded the activities of color-selective neurons in the inferior
      temporal (IT) cortex of two monkeys trained to perform a color categorization
      task, a color discrimination task and a simple fixation task. Many IT neurons
      changed their activity depending upon the task, although color selectivity was
      well conserved. A majority of neurons showed stronger responses during the
      categorization task. Moreover, for the population of IT neurons as a whole,
      signals contributing to performing the categorization task were enhanced. These
      results imply that judgment of color category by color-selective IT neurons is
      facilitated during the categorization task and suppressed during the
      discrimination task as a consequence of task-dependent modulation of their
      activities.

PMID- 17173045
TI  - Attention induces synchronization-based response gain in steady-state visual
      evoked potentials.
AB  - When attention is voluntarily directed to a spatial location, visual sensitivity
      increases at that location. What causes this improved sensitivity? Studies of
      single neuron spike rates in monkeys have provided mixed results in regard to
      whether attending to a stimulus increases its effective contrast (contrast gain)
      or multiplicatively boosts stimulus-driven neural responses (response or activity
      gain). We monitored frequency-tagged steady-state visual evoked potentials
      (SSVEPs) in humans and found that voluntary sustained attention multiplicatively
      increased stimulus-driven population electrophysiological activity. Analyses of
      intertrial phase coherence showed that this attentional response gain was at
      least partially due to the increased synchronization of SSVEPs to stimulus
      flicker. These results suggest that attention operates in a complementary manner
      at different levels; attention seems to increase single-neuron spike rates in a
      variety of ways, including contrast, response and activity gains, while also
      inducing a multiplicative boost on neural population activity via enhanced
      response synchronization.

PMID- 17173046
TI  - Mechanisms of scent-tracking in humans.
AB  - Whether mammalian scent-tracking is aided by inter-nostril comparisons is
      unknown. We assessed this in humans and found that (i) humans can scent-track,
      (ii) they improve with practice, (iii) the human nostrils sample spatially
      distinct regions separated by approximately 3.5 cm and, critically, (iv) scent
      tracking is aided by inter-nostril comparisons. These findings reveal fundamental
      mechanisms of scent-tracking and suggest that the poor reputation of human
      olfaction may reflect, in part, behavioral demands rather than ultimate
      abilities.

PMID- 17173047
TI  - Coherent motion of stereocilia assures the concerted gating of hair-cell
      transduction channels.
AB  - The hair cell's mechanoreceptive organelle, the hair bundle, is highly sensitive
      because its transduction channels open over a very narrow range of displacements.
      The synchronous gating of transduction channels also underlies the active hair
      bundle motility that amplifies and tunes responsiveness. The extent to which the
      gating of independent transduction channels is coordinated depends on how tightly
      individual stereocilia are constrained to move as a unit. Using dual-beam
      interferometry in the bullfrog's sacculus, we found that thermal movements of
      stereocilia located as far apart as a hair bundle's opposite edges showed high
      coherence and negligible phase lag. Because the mechanical degrees of freedom of
      stereocilia are strongly constrained, a force applied anywhere in the hair bundle
      deflects the structure as a unit. This feature assures the concerted gating of
      transduction channels that maximizes the sensitivity of mechanoelectrical
      transduction and enhances the hair bundle's capacity to amplify its inputs.

PMID- 17173048
TI  - Integrative molecular concept modeling of prostate cancer progression.
AB  - Despite efforts to profile prostate cancer, the genetic alterations and
      biological processes that correlate with the observed histological progression
      are unclear. Using laser-capture microdissection to isolate 101 cell populations,
      we have profiled prostate cancer progression from benign epithelium to metastatic
      disease. By analyzing expression signatures in the context of over 14,000
      'molecular concepts', or sets of biologically connected genes, we generated an
      integrative model of progression. Molecular concepts that demarcate critical
      transitions in progression include protein biosynthesis, E26 transformation
      specific (ETS) family transcriptional targets, androgen signaling and cell
      proliferation. Of note, relative to low-grade prostate cancer (Gleason pattern
      3), high-grade cancer (Gleason pattern 4) shows an attenuated androgen signaling
      signature, similar to metastatic prostate cancer, which may reflect
      dedifferentiation and explain the clinical association of grade with prognosis.
      Taken together, these data show that analyzing gene expression signatures in the
      context of a compendium of molecular concepts is useful in understanding cancer
      biology.

PMID- 17173049
TI  - Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are
      associated with autism spectrum disorders.
AB  - SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic
      spines and is a binding partner of neuroligins; genes encoding neuroligins are
      mutated in autism and Asperger syndrome. Here, we report that a mutation of a
      single copy of SHANK3 on chromosome 22q13 can result in language and/or social
      communication disorders. These mutations concern only a small number of
      individuals, but they shed light on one gene dosage-sensitive synaptic pathway
      that is involved in autism spectrum disorders.

PMID- 17173050
TI  - Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only
      infrequently associated with chromosomal aberrations, but it was recently shown
      that most individuals with T-ALL carry activating mutations in the NOTCH1 gene.
      However, the signaling pathways and target genes responsible for Notch1-induced
      neoplastic transformation remain undefined. We report here that constitutively
      active Notch1 activates the NF-kappaB pathway transcriptionally and via the
      IkappaB kinase (IKK) complex, thereby causing increased expression of several
      well characterized target genes of NF-kappaB in bone marrow hematopoietic stem
      cells and progenitors. Our observations demonstrate that the NF-kappaB pathway is
      highly active in established human T-ALL and that inhibition of the pathway can
      efficiently restrict tumor growth both in vitro and in vivo. These findings
      identify NF-kappaB as one of the major mediators of Notch1-induced transformation
      and suggest that the NF-kappaB pathway is a potential target of future therapies
      of T-ALL.

PMID- 17173051
TI  - CD8+ T-cell responses to different HIV proteins have discordant associations with
      viral load.
AB  - Selection of T-cell vaccine antigens for chronic persistent viral infections has
      been largely empirical. To define the relationship, at the population level,
      between the specificity of the cellular immune response and viral control for a
      relevant human pathogen, we performed a comprehensive analysis of the 160
      dominant CD8(+) T-cell responses in 578 untreated HIV-infected individuals from
      KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific
      responses were associated with lowering viremia. Env-specific and
      Accessory/Regulatory protein-specific responses were associated with higher
      viremia. Increasing breadth of Gag-specific responses was associated with
      decreasing viremia and increasing Env breadth with increasing viremia.
      Association of the specific CD8(+) T-cell response with low viremia was
      independent of HLA type and unrelated to epitope sequence conservation. These
      population-based data, suggesting the existence of both effective immune
      responses and responses lacking demonstrable biological impact in chronic HIV
      infection, are of relevance to HIV vaccine design and evaluation.

PMID- 17173053
TI  - The influence of cyclosporin alone, or cyclosporin and methotrexate, on the
      incidence of mixed haematopoietic chimaerism following allogeneic sibling bone
      marrow transplantation for severe aplastic anaemia.
AB  - We previously reported a randomized trial comparing Cyclosporin-A (CsA) and short
      term methotrexate versus CsA alone for graft-versus-host disease (GvHD)
      prophylaxis in 71 patients undergoing allogeneic haematopoietic stem cell
      transplantation (HSCT) from a human leucocyte antigen-identical sibling for
      severe aplastic anaemia (SAA). We found a better survival in the group receiving
      the two-drug prophylaxis regimen with no significant difference in the
      probability of developing GvHD between the two groups. The present study details
      chimaeric analysis and its influence on survival and GvHD occurrence in 45 of the
      original 71 patients in whom serial samples were available. Analysis was carried
      out in a blinded prospective manner. Seventy-two per cent achieved complete donor
      chimaerism (DC), 11% stable mixed chimaerism (SMC) and 17% progressive mixed
      chimaerism (PMC). The overall 5-year survival probability was 82% (+/-11%) with a
      significant survival advantage (P = 0.0009) in DC or SMC compared to those with
      PMC. Chronic GvHD was more frequent in DC patients, whereas no patient with SMC
      developed chronic GvHD. Graft failure occurred in 50% of the PMC group. This
      study demonstrates the relevance of chimaerism analysis in patients receiving
      HSCT for SAA and confirms the occurrence of mixed chimaerism in a significant
      proportion of recipients.

PMID- 17173052
TI  - A single subunit, Dis3, is essentially responsible for yeast exosome core
      activity.
AB  - The conserved core of the exosome, the major eukaryotic 3' --> 5' exonuclease,
      contains nine subunits that form a ring similar to the phosphorolytic bacterial
      PNPase and archaeal exosome, as well as Dis3. Dis3 is homologous to bacterial
      RNase II, a hydrolytic enzyme. Previous studies have suggested that all subunits
      are active 3' --> 5' exoRNases. We show here that Dis3 is responsible for exosome
      core activity. The purified exosome core has a hydrolytic, processive and Mg(2+)
      dependent activity with characteristics similar to those of recombinant Dis3.
      Moreover, a catalytically inactive Dis3 mutant has no exosome core activity in
      vitro and shows in vivo RNA degradation phenotypes similar to those resulting
      from exosome depletion. In contrast, mutations in Rrp41, the only subunit
      carrying a conserved phosphorolytic site, appear phenotypically not different
      from wild-type yeast. We observed that the yeast exosome ring mediates
      interactions with protein partners, providing an explanation for its essential
      function.

PMID- 17173054
TI  - Influence of harvest bacterial contamination on autologous peripheral blood
      progenitor cells post-transplant.
AB  - Microbiological contamination of manipulated blood products, including
      hematopoietic progenitors obtained from peripheral blood, is an infrequent but
      persistent problem in transplant units. The relevance of such contamination in
      causing patient infection has been reported as insignificant, but the effect on
      the post-transplant course has not been well documented. We studied the incidence
      of bacterial contamination in autologous peripheral blood progenitor cell
      transplants in two of the bench processing steps, as well as the repercussions in
      the post-transplant course affecting incidence of infections, transfusion
      requirements and time to engraftment. A total of 365 aphereses performed on 152
      patients were cryopreserved in 617 bags. In 31 of these bags (5.0%), bacterial
      cultures were positive for Coagulase-negative Staphylococcus (31.1%), S.
      epidermidis (21.9%), Corynebacterium sp. (6.3%), S. warneri (6.3%),
      Stenotrophomonas maltophilia (6.3%), Streptococcus sp. (9.4%), Viridans group
      Streptococcus (3.1%) and more than one bacteria (Coagulase-negative
      Staphylococcus plus Corynebacterium) (15.6%). Half of the bags were contaminated
      at the time of freezing and the others at the time of thawing. The 31
      contaminated bags were infused into 17 patients. In five of these the same
      contaminating bacteria was found. No difference between the two groups of
      patients (contaminated and non-contaminated) was found on the day the fever
      started, length of fever, blood transfusion requirements and engraftment, but
      length of hospitalization was significantly greater in patients receiving
      contaminated transplants.

PMID- 17173055
TI  - Polycomb silencing mechanisms and the management of genomic programmes.
AB  - Polycomb group complexes, which are known to regulate homeotic genes, have now
      been found to control hundreds of other genes in mammals and insects. First
      believed to progressively assemble and package chromatin, they are now thought to
      be localized, but induce a methylation mark on histone H3 over a broad chromatin
      domain. Recent progress has changed our view of how these complexes are
      recruited, and how they affect chromatin and repress gene activity. Polycomb
      complexes function as global enforcers of epigenetically repressed states,
      balanced by an antagonistic state that is mediated by Trithorax. These epigenetic
      states must be reprogrammed when cells become committed to differentiation.

PMID- 17173056
TI  - Heterochromatin revisited.
AB  - The formation of heterochromatin, which requires methylation of histone H3 at
      lysine 9 and the subsequent recruitment of chromodomain proteins such as
      heterochromatin protein HP1, serves as a model for the role of histone
      modifications and chromatin assembly in epigenetic control of the genome. Recent
      studies in Schizosaccharomyces pombe indicate that heterochromatin serves as a
      dynamic platform to recruit and spread a myriad of regulatory proteins across
      extended domains to control various chromosomal processes, including
      transcription, chromosome segregation and long-range chromatin interactions.

PMID- 17173057
TI  - Dosage compensation: the beginning and end of generalization.
AB  - The genomes of higher eukaryotes are carefully balanced systems of gene
      expression that compensate for the different numbers of sex chromosomes in the
      two sexes by adjusting gene expression levels. Different strategies for sex
      chromosome dosage compensation have evolved, which all involve modulating
      chromatin structure as a means to fine-tune transcription levels. As data
      accumulate, previous over-simplifications are being revised, and novel features
      of the compensation processes are gaining attention, many of which are of
      sufficient global validity to influence our view on gene expression beyond the
      realm of dosage compensation itself.

PMID- 17173058
TI  - The mouse as a model for human biology: a resource guide for complex trait
      analysis.
AB  - The mouse has been a powerful force in elucidating the genetic basis of human
      physiology and pathophysiology. From its beginnings as the model organism for
      cancer research and transplantation biology to the present, when dissection of
      the genetic basis of complex disease is at the forefront of genomics research, an
      enormous and remarkable mouse resource infrastructure has accumulated. This
      review summarizes those resources and provides practical guidelines for their
      use, particularly in the analysis of quantitative traits.

PMID- 17173059
TI  - Recombination: an underappreciated factor in the evolution of plant genomes.
AB  - Our knowledge of recombination rates and patterns in plants is far from being
      comprehensive. However, compelling evidence indicates a central role for
      recombination, through its influences on mutation and selection, in the evolution
      of plant genomes. Furthermore, recombination seems to be generally higher and
      more variable in plants than in animals, which could be one of the primary
      reasons for differences in genome lability between these two kingdoms. Much
      additional study of recombination in plants is needed to investigate these ideas
      further.

PMID- 17173060
TI  - Bariatric surgery for pediatric extreme obesity: now or later?
AB  - Obesity is a multifactorial disease of epidemic and global proportions that poses
      the most significant threat to the health of our younger generations. Those who
      are the most extremely affected bear the largest burden of health problems. In
      the US, extreme obesity affects approximately 9 million adults and 2 million
      children, and is associated with both immediate health problems and later health
      risk, including premature mortality. Present medical and behavioral interventions
      for extreme obesity in adults and children rarely result in the significant,
      durable weight loss necessary to improve health outcomes, prompting a search for
      more aggressive measures. Weight loss (bariatric) surgery has been advocated as
      an intervention for those with extreme obesity. In adults, bariatric surgery
      results in prolonged weight control and improvement in serious obesity
      comorbidities, namely type 2 diabetes, dyslipidemias, hypertension and
      obstructive sleep apnea syndrome. A surge in weight loss operations for
      adolescents has been observed recently, with a threefold increase in case volumes
      nationwide from 2000 to 2003. Current evidence suggests that after bariatric
      surgery, adolescents lose significant weight and serious obesity-related medical
      conditions and psychosocial status are improved. Thus it is reasonable to propose
      that bariatric surgery performed in the adolescent period may be more effective
      treatment for childhood-onset extreme obesity than delaying surgery for extremely
      obese youth until adulthood. This position has been echoed by a number of groups
      and an independent systematic review. Finally, it is conceivable that bariatric
      surgery performed in adulthood for childhood onset extreme obesity may not be as
      effective for comorbidity treatment as surgery performed earlier during
      adolescence. The purpose of this review is to examine the evidence, which
      supports early rather than later use of bariatric surgery in the treatment of
      extreme obesity, and to present this information in light of the medical and
      surgical risks of bariatric surgery.

PMID- 17173061
TI  - Dietary intake, physical activity and TV viewing as mediators of the association
      of socioeconomic status with body composition: a cross-sectional analysis of
      Australian youth.
AB  - BACKGROUND: There is emerging evidence of socioeconomic gradients in adiposity
      among Australian youth. Behavioral mechanisms for these trends are unexplained.
      METHODS: In total, 194 South Australian children (97 boys, 11.48+/-0.43 years; 97
      girls, 11.60+/-0.38 years) were assessed for pubertal status, stature, weight,
      skinfolds and waist girth. Socioeconomic status (SES) was represented by postcode
      of residence (Socioeconomic Index for Areas) and parent education. Children
      reported moderate-to-vigorous physical activity (MVPA), TV viewing (TV) and
      dietary intake (daily energy intake as a ratio of predicted basal metabolic rate
      (DEI/BMR); and fat intake), using three x 24 h recall. Path analysis (partial
      least-squared method) was used to analyze the independence and interdependence of
      pathways linking SES, anthropometric variables and measured behaviors. RESULTS:
      SES was negatively associated with waist girth and skinfolds in girls, and waist
      girth in boys. In models including behavioral variables, these SES gradients in
      girls were largely unattenuated; accordingly, physical activity and dietary
      intake were not confirmed as mediators of the association of SES and girls'
      adiposity. In boys there was evidence that the negative relationship between SES
      and waist girth was mediated by fat intake. CONCLUSIONS: The inverse
      relationships between SES and girls' adiposity were unexplained by the behavioral
      attributes measured in this study. Mediators of SES gradients in youth adiposity
      remain elusive, and may require intensive methodologies to explicate.

PMID- 17173062
TI  - Functional implication of BMP4 expression on angiogenesis in malignant melanoma.
AB  - Analyses of malignant melanomas revealed a strong expression of bone morphogenic
      proteins (BMPs) and their autocrine effect in promoting cell invasion and
      migration. Here, we report a paracrine effect of BMPs on the vascular network.
      Both BMP2 and BMP4 induced tube formation as well as the migratory efficiency of
      microvascular endothelial cells. Melanoma cells with reduced BMP activity
      attracted less endothelial cells in invasion assays than control cells.
      Furthermore, reduction of BMPs in melanoma cells had a strong effect on
      vasculogenic mimicry. Tube formation on matrigel was analysed for melanoma cells
      as well as in co-cultures of endothelial and melanoma cells. Melanoma cells with
      reduced BMP activity were not capable of forming cord-like structures by
      themselves and additionally inhibited tube formation of the endothelial cells.
      Genes involved in angiogenesis turned out to be strongly downregulated in these
      cell clones. Tumors derived from cells with impaired BMP activity showed reduced
      tumor growth or large necrotic areas owing to lack of angiogenesis in in vivo
      analyses.

PMID- 17173064
TI  - An optimal range of transcription potency is necessary for efficient cell
      transformation by c-Rel to ensure optimal nuclear localization and gene-specific
      activation.
AB  - c-Rel is overexpressed in several B-cell lymphomas and c-rel gene overexpression
      can transform primary chicken lymphoid cells and induce tumors in animals.
      Although c-Rel is generally a stronger transcriptional activator than its viral
      derivative v-Rel, its oncogenic activity is significantly weaker. Among the
      mutations acquired during c-Rel's evolution into v-Rel are deletion of c-Rel's
      transactivation domain 2 (cTAD2) and mutations in cTAD1. Given the critical role
      of the Rel TADs in cell transformation, we investigated how mutations in c-Rel's
      cTAD1 and cTAD2 contribute to its oncogenicity and that of v-Rel. Mutations in
      cTAD2 noticeably increased c-Rel's transforming activity by promoting its nuclear
      localization and gene-specific transactivation, despite an overall decrease in
      kappaB site-dependent transactivation potency. Conversely, substitution of vTAD
      by cTAD1 increased v-Rel's transactivation and transforming efficiencies, whereas
      its substitution by the stronger cTAD2 compromised activation of mip-1beta but
      not irf-4 and was detrimental to cell transformation. These results suggest that
      the Rel TADs differentially contribute to gene-specific activation and that an
      optimal range of transcription potency is necessary for efficient transformation.
      These findings may have important implications for understanding how Rel TAD
      mutations can lead to a more oncogenic phenotype.

PMID- 17173063
TI  - 'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in
      resistance to the small-molecule Bcl-2/Bcl-XL inhibitor ABT-737.
AB  - ABT-737 is a subnanomolar inhibitor of the antiapoptotic proteins Bcl-2, Bcl-X(L)
      and Bcl-w. Although ABT-737 triggers extensive cell death in many small-cell lung
      carcinoma (SCLC) cell lines, some of the SCLC cell lines and the majority of the
      cancer cell lines derived from other solid tumors were found to be resistant to
      ABT-737. To better understand the mechanism of resistance to ABT-737, we screened
      a short interfering RNA library consisting of short interfering RNA against 4000
      'druggable' targets in an SCLC-derived cell line, NCI-H196. By comparing the
      knockdowns with phenotypes, all of the three top 'hits' from the screen were
      found to result from off-target gene silencing. Interestingly, the three off
      target siRNAs were found to knock down an antiapoptotic Bcl-2 family protein Mcl
      1 owing to the complementation between their seed regions with the 3'
      untranslated region (3' UTR) of Mcl-1. Furthermore, reducing the level of Mcl-1
      using siRNAs or the small-molecule compounds Bay43-9006 and Seliciclib was
      sufficient to overcome the resistance to ABT-737 in the resistant SCLC cell line
      and cancer cell lines derived from other solid tumors. These results provide
      further evidence that Mcl-1 is the major factor that causes resistance to ABT-737
      in cancer cells derived from diverse solid tumors, and the combination of Mcl-1
      downregulating agents with ABT-737 could be potent therapeutic regimens for
      patient with ABT-737-resistant SCLC and many other types of solid tumors.

PMID- 17173065
TI  - Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and
      Rb1 knockout mice.
AB  - To identify possible genetic interactions between the mechanisms of tumor
      suppression of menin and pRb, we intercrossed mice with targeted deletions of
      Men1 and Rb1, and compared tumor development in cohorts of animals carrying
      single or dual mutations of these tumor-suppressor genes. In mice lacking one
      copy of Men1, pancreatic islet and anterior pituitary adenomas are common. In
      animals lacking one copy of Rb1, intermediate pituitary and thyroid tumors occur
      at high frequency, with less frequent development of pancreatic islet hyperplasia
      and parathyroid lesions. In mice heterozygous for both Men1 and Rb1, pancreatic
      hyperplasia and tumors of the intermediate pituitary and thyroid occurred at high
      frequency. Serum measurements of calcium and glucose did not vary significantly
      between genotypic groups. Loss of heterozygosity at the Rb1 locus was common in
      pituitary and thyroid tumors, whereas loss of menin was observed in pancreatic
      and parathyroid lesions. The tumor spectrum in the double heterozygotes was a
      combination of pathologies seen in each of the individual heterozygotes, without
      decrease in age of onset, indicating independent, non-additive effects of the two
      mutations. Together with the lack of increased tumor spectrum, this suggests that
      menin and pRb function in a common pathway of tumor suppression.

PMID- 17173066
TI  - Semaxinib (SU5416) as a therapeutic agent targeting oncogenic Kit mutants
      resistant to imatinib mesylate.
AB  - Activating mutations in the Kit receptor are frequently observed in various
      malignancies, pointing Kit as a molecule of interest for drug inhibition. When
      mutated on Asp 816 (corresponding to Asp 814 in the mouse), as preferentially
      found in human mastocytosis and acute myeloid leukemia, Kit became non-sensitive
      to imatinib mesylate (Gleevec). Erythroleukemic cells isolated from Spi-1/PU.1
      transgenic mice express Kit mutated at codon 814 (Kit(D814Y) or Kit(D814V)) or
      codon 818 (Kit(D818Y)). Using these cells in vitro, we demonstrate that the
      tyrosine kinase inhibitor SU5416 (Semaxinib) induces growth arrest and apoptosis
      independent of the mutation type by inhibiting the functions of Kit, including
      Kit autophosphorylation and activation of Akt, Erk1/Erk2 and Stat3 downstream
      signaling pathways. These findings indicate that SU5416 may be a promising tool
      to kill cancer cells driven by Kit oncogenic mutations that are resistant to
      treatment with imatinib mesylate.

PMID- 17173067
TI  - A novel anticancer agent ARC antagonizes HIV-1 and HCV.
AB  - Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) pose major public
      health concerns worldwide. HCV is clearly associated with the occurrence of
      hepatocellular carcinoma, and recently HIV infection has also been linked to the
      development of a multitude of cancers. Previously, we identified a novel
      nucleoside analog transcriptional inhibitor ARC (4-amino-6-hydrazino-7-beta-D
      ribofuranosyl-7H-pyrrolo[2,3-d]-pyrimidine-5-carboxamide) that exhibited
      proapoptotic and antiangiogenic properties in vitro. Here, we evaluated the
      effect of ARC on HIV-1 transcription and HCV replication. Using reporter assays,
      we found that ARC inhibited HIV-1 Tat-based transactivation in different cell
      systems. Also, using hepatoma cells that harbor subgenomic and full-length
      replicons of HCV, we found that ARC inhibited HCV replication. Together, our data
      indicate that ARC could be a promising candidate for the development of antiviral
      therapeutics against HIV and HCV.

PMID- 17173068
TI  - Reduction of apoptosis in Rb-deficient embryos via Abl knockout.
AB  - The retinoblastoma protein RB regulates cell proliferation, differentiation and
      apoptosis. Homozygous knockout of Rb in mice causes embryonic lethality owing to
      placental defects that result in excessive apoptosis. RB binds to a number of
      cellular proteins including the nuclear Abl protein and inhibits its tyrosine
      kinase activity. Ex vivo experiments have shown that genotoxic or inflammatory
      stress can activate Abl kinase to stimulate apoptosis. Employing the Rb-null
      embryos as an in vivo model of apoptosis, we have shown that the genetic ablation
      of Abl can reduce apoptosis in the developing central nervous system and the
      embryonic liver. These results are consistent with the inhibitory interaction
      between RB and Abl, and provide in vivo evidence for the proapoptotic function of
      Abl.

PMID- 17173069
TI  - Inhibition of BCL11B expression leads to apoptosis of malignant but not normal
      mature T cells.
AB  - The B-cell chronic lymphocytic leukemia (CLL)/lymphoma 11B gene (BCL11B) encodes
      a Kruppel-like zinc-finger protein, which plays a crucial role in thymopoiesis
      and has been associated with hematopoietic malignancies. It was hypothesized that
      BCL11B may act as a tumor-suppressor gene, but its precise function has not yet
      been elucidated. Here, we demonstrate that the survival of human T-cell leukemia
      and lymphoma cell lines is critically dependent on Bcl11b. Suppression of Bcl11b
      by RNA interference selectively induced apoptosis in transformed T cells whereas
      normal mature T cells remained unaffected. The apoptosis was effected by
      simultaneous activation of death receptor-mediated and intrinsic apoptotic
      pathways, most likely as a result of tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) upregulation and suppression of the Bcl-xL antiapoptotic
      protein. Our data indicate an antiapoptotic function of Bcl11b. The resistance of
      normal mature T lymphocytes to Bcl11b suppression-induced apoptosis and
      restricted expression pattern make it an attractive therapeutic target in T-cell
      malignancies.

PMID- 17173070
TI  - E2F regulates DDB2: consequences for DNA repair in Rb-deficient cells.
AB  - DDB2, a gene mutated in XPE patients, is involved in global genomic repair
      especially the repair of cyclobutane pyrimidine dimers (CPDs), and is regulated
      by p53 in human cells. We show that DDB2 is expressed in mouse tissues and
      demonstrate, using primary mouse epithelial cells, that mouse DDB2 is regulated
      by E2F transcription factors. Retinoblastoma (Rb), a tumor suppressor critical
      for the control of cell cycle progression, regulates E2F activity. Using Cre-Lox
      technology to delete Rb in primary mouse hepatocytes, we show that DDB2 gene
      expression increases, leading to elevated DDB2 protein levels. Furthermore, we
      show that endogenous E2F1 and E2F3 bind to DDB2 promoter and that treatment with
      E2F1-antisense or E2F1-small interfering RNA (siRNA) decreases DDB2
      transcription, demonstrating that E2F1 is a transcriptional regulator for DDB2.
      This has consequences for global genomic repair: in Rb-null cells, where E2F
      activity is elevated, global DNA repair is increased and removal of CPDs is more
      efficient than in wild-type cells. Treatment with DDB2-siRNA decreases DDB2
      expression and abolishes the repair phenotype of Rb-null cells. In summary, these
      results identify a new regulatory pathway for DDB2 by E2F, which does not require
      but is potentiated by p53, and demonstrate that DDB2 is involved in global repair
      in mouse epithelial cells.

PMID- 17173071
TI  - The Werner syndrome protein is required for recruitment of chromatin assembly
      factor 1 following DNA damage.
AB  - The Werner syndrome protein (WRN) and chromatin assembly factor 1 (CAF-1) are
      both involved in the maintenance of genome stability. In response to DNA-damaging
      signals, both of these proteins relocate to sites where DNA synthesis occurs.
      However, the interaction between WRN and CAF-1 has not yet been investigated. In
      this report, we show that WRN interacts physically with the largest subunit of
      CAF-1, hp150, in vitro and in vivo. Although hp150 does not alter WRN catalytic
      activities in vitro, and the chromatin assembly activity of CAF-1 is not affected
      in the absence of WRN in vivo, this interaction may have an important role during
      the cellular response to DNA replication fork blockage and/or DNA damage signals.
      In hp150 RNA-mediated interference (RNAi) knockdown cells, WRN partially formed
      foci following hydroxyurea (HU) treatment. However, in the absence of WRN, hp150
      did not relocate to form foci following exposure to HU and ultraviolet light.
      Thus, our results demonstrate that WRN responds to DNA damage before CAF-1 and
      suggest that WRN may recruit CAF-1, via interaction with hp150, to DNA damage
      sites during DNA synthesis.

PMID- 17173072
TI  - Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma.
AB  - BIC is a primary microRNA (pri-miR-155) that can be processed to mature miR-155.
      In this study, we show the crucial involvement of protein kinase C (PKC) and
      nuclear factor-kappaB (NF-kappaB) in the regulation of BIC expression upon B-cell
      receptor triggering. Surprisingly, Northern blot analysis did not reveal any miR
      155 expression upon induction of BIC expression in the Burkitt lymphoma-derived
      Ramos cell line, whereas other microRNAs were clearly detectable. Ectopic
      expression of BIC in Ramos and HEK293 cells resulted in miR-155 expression in
      HEK293, but not in Ramos cells, suggesting a specific block of BIC to miR-155
      processing in Ramos. In line with the results obtained with Ramos, lack of miR
      155 expression after induction of BIC expression was also observed in other
      Burkitt lymphoma cell lines, indicating a generic and specific blockade in the
      processing of BIC in Burkitt lymphoma. In contrast, induction of BIC expression
      in normal tonsillar B cells resulted in very high levels of miR-155 expression
      and induction of BIC expression in Hodgkin's lymphoma cell lines. It also
      resulted in elevated levels of miR-155. Our data provide evidence for two levels
      of regulation for mature miR-155 expression: one at the transcriptional level
      involving PKC and NF-kappaB, and one at the processing level. Burkitt lymphoma
      cells not only express low levels of BIC, but also prevent processing of BIC via
      an, as yet, unknown mechanism.

PMID- 17173073
TI  - Overload of the heat-shock protein H11/HspB8 triggers melanoma cell apoptosis
      through activation of transforming growth factor-beta-activated kinase 1.
AB  - Molecular therapeutics is a recognized promising approach for melanoma, but
      relevant target genes remain elusive. We report that overload of the recently
      cloned H11/HspB8 induces apoptosis in 55% of examined melanoma cultures.
      Apoptosis was determined by activation of caspases-9 and -3 and terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), and was not
      seen in normal melanocytes. It was associated with H11/HspB8 complexation with
      transforming growth factor-beta-activated kinase (TAK) 1 and activation of TAK1
      and p38 mitogen activated protein 3 kinases. TAK1 was not bound, nor activated by
      the H11/HspB8 mutant W51C, which has dominant antiapoptotic activity. beta
      Catenin was phosphorylated by activated TAK1, inhibiting its nuclear accumulation
      and mictophthalmia-associated transcription factor and cyclin dependent kinase 2
      expression. The dominant-negative TAK1 mutant K63W inhibited beta-catenin
      phosphorylation and caspase activation. The data indicate that H11/HspB8 overload
      causes melanoma growth arrest and apoptosis through TAK1 activation and suggest
      that H11/HspB8 is a promising molecular therapy target.

PMID- 17173075
TI  - c-Src modulates ErbB2 and ErbB3 heterocomplex formation and function.
AB  - Overexpression and/or gene amplification of c-Src and members of the epidermal
      growth factor receptor (EGFR/ErbB) family have been implicated in the
      pathogenesis of breast cancer. Although members of the EGFR family are known to
      form heterocomplexes with one another, c-Src has also been shown to physically
      interact with members of this family in breast cancer cell lines and tumors. This
      paper investigates the role of c-Src in modulating the physical and functional
      interaction between ErbB2 and ErbB3, two family members that preferentially
      associate with one another and together exhibit high oncogenic potential. We show
      that overexpressed wild-type c-Src enhances heterocomplex formation of ErbB2 and
      ErbB3 that results in increased basal and/or heregulin-induced activation of
      receptors, and their downstream intracellular effectors. Expression of a kinase
      inactive form of c-Src (K(-) c-Src) or pharmacological inhibition of c-Src by PP2
      negatively affects these events. Furthermore, cellular motility and anchorage
      independent growth promoted by the ErbB2/ErbB3 heterocomplex are dependent upon c
      Src, as demonstrated by the effects of K(-) c-Src overexpression or treatment
      with PP2. In contrast to previous studies that defined a role for c-Src
      downstream of ErbB2/ErbB3, the current work suggests an upstream mechanism,
      whereby c-Src enhances ErbB2/ErbB3 signaling and biological functions by
      positively modulating the association between ErbB2 and ErbB3.

PMID- 17173074
TI  - Transcriptional upregulation of p57 (Kip2) by the cyclin-dependent kinase
      inhibitor BMS-387032 is E2F dependent and serves as a negative feedback loop
      limiting cytotoxicity.
AB  - In spite of the fact that cyclin-dependent kinase (cdk) inhibiting drugs are
      potent transcriptional repressors, we discover that p57 (Kip2, CDKN1C)
      transcription is significantly upregulated by three small molecule cdk
      inhibitors, including BMS-387032. Treatment of MDA-MB-231 breast cancer cells
      with BMS-387032 led to a stabilization of the E2F1 protein that was accompanied
      by significant increases in the p57 mRNA and protein. This increase did not occur
      in an E2F1-deficient cell line. An E2F1-estrogen receptor fusion protein
      activated the endogenous p57 promoter in response to hydroxytamoxifen treatment
      in the presence of cycloheximide. Luciferase constructs driven by the p57
      promoter verified that upregulation of p57 mRNA by BMS-387032 is transcriptional
      and dependent on E2F-binding sites in the promoter. Expression of exogenous p57
      significantly decreased the fraction of cells in S phase. Furthermore, p57
      deficient MDA-MB-231 cell lines were significantly more sensitive to BMS-387032
      induced apoptosis than controls. The results presented in this manuscript
      demonstrate that small molecule cdk inhibitors transcriptionally activate p57
      dependent upon E2F1 and that this activation in turn serves to limit E2F1's death
      inducing activity.

PMID- 17173077
TI  - [Preparation and identification of monoclonal antibodies against human programmed
      cell death 10 (PDCD10)].
AB  - OBJECTIVE: To obtain monoclonal antibodies against programmed cell death 10
      (PDCD10) for further study of the structure and function of PDCD10 protein.
      METHODS: Balb/c mice were immunized with recombinant PDCD10, hybridoma cell lines
      secreting monoclonal antibodies against PDCD10 were screened by regular cell
      fusion and subcloning approach. The specificities of these monoclonal antibodies
      were determined by ELISA, Western blotting and Immunofluorescence assay. RESULTS:
      Three hybridoma cell lines (5G1, 4F7 and 3H5) stable in secreting specific
      monoclonal antibodies were successfully obtained. Subclass of IgG belonged to
      IgG1 (4F7 and 5G1) and IgG2b (3H5), respectively. The ascite titers of these
      monoclonal antibodies reached 1:10(7). They could specifically bind to
      recombinant PDCD10 and endogenous and overexpressed PDCD10 proteins proved by
      ELISA and Western blotting. They failed to react with E.coli lysates and
      glutathione S-transferase (GST). In addition, these three monoclonal antibodies
      could recognize different epitopes of PDCD10 proteins assessed by immune
      fluorescence competitive binding assay. Both endogenous and overexpressed PDCD10
      protein mainly located in the nucleus. CONCLUSION: Monoclonal antibodies against
      PDCD10 with high titers and specificity have been successfully prepared, which
      has laid the foundation for further study of PDCD10 protein.

PMID- 17173076
TI  - [Vasorelaxant effect of sulfur dioxide derivatives on isolated aortic rings of
      rats and its mechanisms].
AB  - OBJECTIVE: To investigate the vasorelaxant effect of sulfur dioxide (SO(2)) on
      isolated aortic rings of rats in vitro and its relaxation mechanisms. METHODS: We
      perffused the isolated aortic rings of rats, and precontracted the rings with
      noradrenaline (NE), then observed the relaxant reactivity of SO(2) derivatives,
      mixture of sulfite and hydrogen sulfite [Na(2)SO(3)/NaHSO(3) 3:1(amount of
      substance)], to the aortic rings. Meanwhile, we studied the influence of
      glibenclamide and nicardipine, blockers of K(ATP) and L-calcium channels, on the
      vasorelaxant reactivity of SO(2) derivatives. We further incubated the aortic
      rings with hydroxamate (HDX), the inhibitor of SO(2) endogenous generating
      enzymes, and SO(2) derivatives (4 mmol/L) in vitro, then observed the contraction
      of the aortic rings to NE. RESULTS: Isolated aortic rings of rats exhibited
      relaxant reactivity to Na(2)SO(3)/NaHSO(3) (0-12 mmol/L) in a concentration
      dependent manner. IC(50) of the relaxation curve was (7.28+/-0.12) mmol/Liand
      Emax was 78.79%+/-3.24%. Glibenclamide (1x10(-6) mol/L) inhibited the
      vasorelaxation to low dose Na(2)SO(3)/NaHSO(3) (<or=4 mmol/L), whereas it failed
      to inhibit the vasorelaxation to high dose of Na(2)SO(3)/NaHSO(3) (>6 mmol/L).
      Nicardipine (1x10(-9) mol/L) could decrease the contraction of the rings to NE,
      and even could inhibit the relaxation of Na(2)SO(3)/NaHSO(3) almost completely.
      The inhibition of the endogenous SO(2) production with HDX (1x10(-4) mol/L),
      resulted in an increase in the contraction of rings. The contraction curve to NE
      shifted to the left, and IC(50) also changed from (6.48+/-0.84)x10(-7) mol/L to
      (3.97+/-1.63)x10(-7) mol/L (P<0.01). However, after the incubation of aortic
      rings with Na(2)SO(3)/NaHSO(3) (4 mmol/L), the contraction curve to NE shifted to
      the right, and IC(50) changed from (6.48+/-0.84)x10(-7) mol/L to (4.93+/
      0.81)x10(-5) mol/L (P<0.01). CONCLUSION: SO(2) could relax vascular smooth
      muscles, and the mechanism might be associated with calcium channels and K(ATP)
      channels, suggesting that endogenous SO(2) could modulate the cardiovascular
      function.

PMID- 17173078
TI  - [In vivo transfer of human chemokine-like factor 1 gene increases peripheral
      blood CD34+ stem cells after myocardial infarction in rats].
AB  - OBJECTIVE: To assess the influence of different doses of CKLF1 plasmid on the
      dynamics and magnitude of the mobilization of the mobilization bone of marrow
      stem cells in a rat AMI model. METHODS: Different doses of plasmid DNA encoding
      CKLF1 gene, empty plasmid or saline were injected into male SD rats
      intramuscularly with in vivo electroporation. Rats were subjected to left
      coronary artery ligation 6 days after gene transfer. Peripheral blood samples
      were drawn and CD34+ cells were assayed by FACS calibur flow-cytometer. The
      changes in absolute number of CD34+ cells were evaluated. RESULTS: Expressions of
      CKLF1 mRNA and protein were detected in the injection site 7 days after gene
      transfer. Five days after gene transfer, the CD34+ cells numbers in CKLF1 groups
      were significantly higher than those in empty plasmid group, especially in CKLF1
      100 microg group (16.63x10(6)/L vs 4.98x10(6)/L, P<0.01). On the 5-7 days, the
      CD34+ cell numbers in CKLF1 groups reached the peak and the peak number was 3.88
      times that of baseline in CKLF1 100 microg group (P<0.01). After AMI, the cell
      numbers of 1 day to 7 days were significantly higher than those of the baseline
      in empty plasmid group and saline group. In comparison to empty plasmid group,
      CKLF1 groups were associated with still higher numbers of cells 1 day after AMI
      (P< 0.05), especially in CKLF1 100 microg group (14.61x10(6)/L vs 7.85x10(6)/L,
      P<0.01). CONCLUSION: CKLF1 gene transfer significantly increases the mobilization
      of CD34+ stem cells in acute myocardial infarction rats.

PMID- 17173079
TI  - [HLA expression in human fetal bone marrow mesenchymal stem cells].
AB  - OBJECTIVE: To investigate the expression of human leukocyte antigens (HLA) in
      human fetal bone marrow mesenchymal stem cells (MSCs) after long time culture as
      well as the changes in response to interferon-gamma (IFN-gamma) treatment.
      METHODS: Human fetal MSCs were collected from 23 to 24-weeks-old fetues with the
      approval of Ethic Committee of Peking University Health Science Center. The cells
      of passage 5 and passage 12 were analyzed for HLA expression before and after IFN
      gamma (50 microg/L) treatment by flow cytometry at different time points. The
      passage 5 cells were also treated with an additional dose of IFN-gamma (5
      microg/L) and the HLA expression was analyzed 24, 48, 72, 96 and 120 h after
      treatment. RT-PCR was used to evaluate HLA-G and HLA-E expression at mRNA level
      in human fetal MSCs. RESULTS: Flow cytometry results showed that fetal MSCs
      expressed high level of HLA class I (HLA-I) antigen, but extremely low level of
      HLA class II (HLA-II) antigen. The percentage of HLA-I positive MSCs in total
      MSCs was approximately over 50%, while that of HLA-II positive MSCs in total MSCs
      was less than 10%. IFN-gamma (50 microg/L) enhanced the HLA-I and HLA-II
      expression in a time dependent manner and increased the percentage of HLA-I
      positive cells in both passage 5 and passage 12 cells but preferably in passage 5
      cells. The enhanced HLA-II expression was seen 48 h after IFN-gamma treatment in
      passage 5 cells (59.9%) but 72 h in passage 12 cells (48.1%). The treatment of 5
      microg/L IFN-gamma also increased percentage of HLA-I and HLA-II positive MSCs,
      but with a relatively less extent compared to the 50microg/L IFN-gamma treatment
      group. RT-PCR result indicated HLA-G and HLA-E were expressed at mRNA level in
      human fetal MSCs. CONCLUSION: Human fetal MSCs can be induced to express both HLA
      class I and class II antigens by IFN-gamma. The long time culture might reduce
      the IFN-gamma effects. Human fetal MSCs express HLA-G and HLA-E at mRNA level.

PMID- 17173080
TI  - [Change in ghrelin level with the amelioration of glucose and lipid metabolic
      disorder in OLETF rats].
AB  - OBJECTIVE: To explore the exact role of ghrelin in glyco- and lipo-metabolism.
      METHODS: We compared the levels of ghrelin mRNA in gastric tissue, ghrelin in
      gastric tissue and plasma among LETO rats( non diabetes, n=10), OLETF rats( type
      2 diabetes, n=10), OLETF/M rats( OLETF rats managed with Metformin at the dose of
      100 mg/kg weight, n=10) and OLETF/F rats( OLETF rats managed with Fenofibrate at
      the dose of 20 mg/kg weight, n=10). The levels of ghrelin mRNA were tested by
      Northern blotting, and the ghrelin content in gastric tissue and plasma detected
      by RIA. RESULTS: At the age of 30 weeks, the ghrelin fasting plasma levels of
      OLETF rats were lower than those of LETO rats(37.49+/-6.42 vs 58.52+/-5.85,
      P<0.05). The fasting blood plasma ghrelin levels of OLETF/M groups showed an
      increased tendency, but the difference of the fasting blood plasma ghrelin levels
      to those of the untreated OLETF rats were not noticeable(49.65+/-6.76 vs 37.49+/
      6.42,P>0.05). However, the fasting blood plasma ghrelin levels of OLETF/F group
      were more than those that of the untreated OLETF rats (62.02+/-7.35 vs 37.49+/-
      6.42,P<0.05). The mRNA and polypeptide levels of ghrelin in stomach tissue had no
      marked difference in the 4 groups at the age of 17 weeks. At the age of 30 weeks,
      the difference of mRNA(1.18+/-0.06 vs 1.27+/-0.05,P<0.05) and polypeptide
      (114.77+/- 31.65 vs 152.87+/-18.24, P<0.05) between OLETF group and LETO group
      had been observed. Metformin didn't influence the mRNA and polypeptide levels of
      ghrelin in stomach tissue markedly. Howere, the polypeptide (161.75+/-23.61 vs
      114.77+/-31.65, P<0.05) and mRNA(1.36+/-0.09 vs 1.18+/-0.06,P<0.05) levels of
      ghrelin in stomach tissue of OLETF/F group were markedly higher than those of
      stomach tissue ghrelin in the untreated OLETF group. CONCLUSION: Our data
      demonstrate that ghrelin may play a role in protective, compensative and negative
      feedback regulation in the disorder of glucose and lipid metabolism.

PMID- 17173081
TI  - [Effects of globular adiponectin, glucose and free fatty acid on AMPK and ACC
      phosphorylation in INS-1 beta cells].
AB  - OBJECTIVE: To investigate effects of glucose and free fatty acid at different
      concentrations on phosphorylation of adenosine-5'-monophosphate activated protein
      kinase(AMPK) and acetyl CoA carboxylase (ACC) in INS-1 cells, and effects of
      globular adiponectin on phosphorylation of AMPK and ACC. METHODS: INS-1 cells
      were cultured and treated with 5 mmol/L glucose or 0.25 mmol/L free fatty acids,
      and time courses and dose responses of different dosages of glucose and fatty
      acid on phosphorylation of AMPK and ACC were measured. We measured the effects of
      the pharmacological AMPK activator AICAR (5-aminoimidazole-4-carboxamide
      riboside) and globular adiponectin on phosphorylation of AMPK and ACC. RESULTS:
      Glucose and fatty acid at different concentrations inhibited the phosphorylation
      of AMPK and ACC at the end of 60 min, but AICAR increased the phosphorylation of
      AMPK and ACC significantly, while 2.5 mg/L globular adiponectin increased the
      phosphorylation of AMPK and ACC by 23% (P<0.05) and 50% (P<0.05) respectively, at
      baseline. In the presence of 5 mmol/L glucose, globular adiponectin increased
      AMPK and ACC phosphorylation by 1.4-fold (P<0.05) and 3-fold (P<0.01),
      respectively. In the presence of 0.25 mmol/L free fatty acid, globular
      adiponectin increased AMPK and ACC phosphorylation 3-fold (P<0.05) and 5-fold
      (P<0.01) respectively. CONCLUSION: In cultured islet cells, glucose and free
      fatty acid at various concentrations inhibit the phosphorylation of AMPK and ACC,
      but AICAR and globular adiponectin 2.5 mg/L increase the phosphorylation level.
      This may constitute a mechanism to increase fatty acid oxidation and decrease
      triglyceride accumulation in islet beta-cells.

PMID- 17173082
TI  - [Analysis and state of HCV genotype 6a infection].
AB  - OBJECTIVE: To investigate the infection state of hepatitis C virus genotype 6a in
      China. METHODS: Three (95, 126, 150)HCV genotype 6a serum samples were identified
      by digesting 5'NCR with compound enzyme method. Then, HCV 5'NCR and NS5B
      fragments were amplified from these samples by RT-PCR assay and sequenced. The
      phylogenetic trees of the samples were analyzed and compared with 24 HCV complete
      gene sequences from GenBank. RESULTS: The sequencing reports on 5'NCR showed "CA"
      bases in 3 serum samples (95,126,150) were inserted into -145 site, and the
      sequences of 3 serum samples had the highest homology with sequence Y12083(
      0.934, 0.930, and 0.926, respectively). The results of the phylogenetic trees
      suggested these 3 serum samples belonged to HCV genotype 6a. The sequencing
      reports on NS5B showed the 3 serum samples also had the highest homology with HC
      J4(0.934, 0.930, and 0.926, respectively), and the results of the phylogenetic
      trees suggested these 3 serum samples belonged to HCV genotype 1b. To exclude the
      influence of amplification efficiency of primers, NS5B fragments were amplified
      by HCV genotype 6a specific primers and no amplification products appeared.
      CONCLUSION: There are different results of HCV genotype by analyzing 5'NCR and
      NS5B in 3 samples infected with HCV genotype 6a. It may be related with gene
      recombination. It suggests HCV genotype should be analyzed on more than two
      regions.

PMID- 17173083
TI  - [Protective effect of heme oxygenase-1 and its reaction product, carbon monoxide
      on acute liver injury induced by carbon tetrachloride in rats].
AB  - OBJECTIVE: To investigate the protective role of heme oxygenase-1 and its
      reaction product, carbon monoxide against acute liver injury induced by carbon
      tetrachloride in rats. METHODS: Thirty male Sprague-Dawley rats were randomly
      divided into six groups with five in each. The control group received a single
      dose of corn oil injection. Carbon tetrachloride was injected intraperitoneally
      (i.p) to establish acute liver injury models in rats. Hemin(50 micromol/kg) was
      administered i.p. 12 hours before CCl(4) treatment, with an aim to induce HO-1
      protein expression in the liver of rats. Carbon monoxide was injected i.p. 12
      hours prior to CCl(4) injection, resulting in about 8%-12% carboxyhemoglobin
      concentration in vivo. The expression of HO-1 in the liver of hemin-treated rats
      was determined by western blot method at different time points. At 24 h after
      carbon tetrachloride administration, all rats were sacrificed to collect blood
      samples for the examination of ALT, AST levels and to remove liver tissues for
      analysis of MDA concentration, SOD activity and caspase-3 activity as well as TNF
      alpha contents. In addition, histopathological changes were investigated and
      hepatocyte apoptosis was detected by TUNEL method. RESULTS: The administration of
      carbon tetrachloride to rats caused a marked hepatic damage, characterized by
      significant elevation of serum ALT, AST levels(2 136.3+/-163.4 U, 1 422.7+/-221.7
      U) and liver MDA content(5.28+/-0.93 micromol/g), caspase-3 activity (optical
      density value 4.69+/-1.02) and TNF-alpha level(256.3+/-27.3 ng/L) combined with a
      remarkable reduction in liver SOD activity (45.9+/-14.8 U/mg) as compared with
      the control rats. Histopathological observations revealed severe damage in the
      liver and prominent hepatocyte apoptosis took place in CCl(4) -treated rats.
      However, pretreatment with hemin could induce high expression of HO-1 protein and
      exert potent protective effects against liver injury, as demonstrated by a
      significant decrease in ALT, AST levels(287.1+/-24.3 U, 246.2+/- 21.7 U) and MDA
      concentration(3.27+/-1.34 micromol/g), reduction in caspase-3 activity(optical
      density value 2.49+/-1.47) and TNF-alpha level(132.6+/-19.5 ng/L), as compared
      with the CCl(4) -treated rats. Moreover, hepatocyte apoptosis and liver injury
      were both attenuated remarkably in the liver of rats pretreated with hemin. In
      contrast to hemin administration, single injection of exogenous CO produced the
      same protective effects, as indicated by the remarkable reduction of ALT, AST
      levels and caspase-3 activity and TNF-alpha levels. CONCLUSION: The above results
      suggest that HO-1/CO system has a potent protective effect on acute liver injury
      induced by carbon tetrachloride in rats. Induction of HO-1 expression and low
      concentration of CO can inhibit the progress of hepatic damage, which might be
      due to the alleviation of lipid peroxidation and reduction of caspase-3 activity
      or inhibition of TNF-alpha level.

PMID- 17173084
TI  - [Construction of recombinant adenoviral vector containing gene of EWS-FLI1 and
      antitumor immunity of its modified dentritic cell in vitro].
AB  - OBJECTIVE: To construct an adenoviral vector containing cDNA of EWS-FLI1 and
      detect its expression in peripheral blood mononeuclear cell(PBMC). To Investigate
      the antitumor immunity in vitro of the EWS-FLI1 gene modified-dendritic cells.
      METHODS: The EWS-FLI1 cDNA in plasmid Pec1/ EWS-FLI1 was digested and subcloned
      into the shuttle plasimid padtrack-cmv. The shuttle plasmid and the bone plasmid
      pADeasy-1 were cotransformed into BJ5183 cells. The recombinant plasmid was
      generated by homologous recombination in BJ5183 cells. The positive clone was
      obtained by digestion and electrophoresis. Transforming the recombinant plasmid
      into "293 cells" by lipofectamine method. Adenoviruses with high titer and purity
      were obtained by amplifying in the"293 cells" on a large scale and ultra
      centrifugation in CsCL step gradient solutions. The cytotoxic activity of
      stimulated T cells to Ewing sarcoma cells was detected by (51)Cr release assay.
      RESULTS: PCR showed that the adenovirus contained EWS-FLI1 cDNA. After the PBMC
      were transfected by Ad EWS-FLI1, the EWS-FLI1 mRNA was detected by RT-PCR. The
      antigen-specific CTL was induced successfully by the EWS-FLI1 gene modified-DC.
      The vigorous antigen-specific CTL response against A673 cells was detected by
      (51)Cr release assay. The killing percentage was 35.18%+/-0.0128% at effector
      target ratio 40:1, which was more efficient than that of the control. CONCLUSION:
      The recombinant adenovirus was successfully constructed and could efficient
      express EWS-FLI1 in PBMC. After T lymphocytes were stimulated by DCs modified
      with EWS-FLI1 gene, the specific CTL response against Ewing's sarcoma cell line A
      673 in vitro was observed successfully. (51)Cr release assay showed that there
      was significant difference between the experimental group and the control group.

PMID- 17173086
TI  - [Immune regulating activity of a novel organoselenium compound ethaselen-1 in
      C57/BL mice].
AB  - OBJECTIVE: To detect the Immune regulating activity of ethaselen-1 (Eb1), a novel
      organoselenium compound, in C57/BL mice transplanted with Lewis lung cancer(LLC).
      METHODS: The LLC transplanted C57/BL mice models were established, and the mice
      was randomly divided into four groups, including high dose Eb1 group (25.0
      mg/kg),low dose Eb1 group (12.5 mg/kg), positive control group (levamisole, LMS,
      2.0 mg/kg) and negative control group(solvent). Intraperitoneal injections (ip.)
      of the four pharmaceuticals were performed once a day through the abdominal wall
      separately, from the second to the eighth day after cancer was transplanted. On
      the eleventh day, six mice of each group were killed and relative weight of
      spleen, transforming activity of spleen lymphocytes, NK cell activity, LAK cell
      activity and percentage of CD4(+)CD8(+)T lymphocyte were detect. RESULTS:
      Compared with the control group, high dose Eb1 could obviously increase the
      relative weight of spleen (150.59% and 122.55%), transforming activity of spleen
      lymphocytes(162.25% and 561.98%), NK cell activity(78.60% and 219.42%) and
      percentage of CD4(-)/CD8(+) T lymphocyte(104.72% and 105.87%) in normal mice and
      LLC mice. Compared with the control group, high dose Eb1 could also increase LAK
      cell activity of LLC mice by 195.11%. CONCLUSION: The novel organoselenium
      compound Eb1 has immune regulating activity in vivo.

PMID- 17173085
TI  - [Long-term effects of neonatal recurrent seizures on gamma-aminobutyric acid A
      receptor alpha1 and gamma2 subunit expressions in the rat brain].
AB  - OBJECTIVE: To investigate the long-term effects of flurothyl-induced neonatal
      recurrent seizures on GABA A receptor (GABA(A)R) alpha1 and gamma2 subunit
      expressions in adult rat brain, and discuss the relationship between these
      alterations of GABA(A)R subunits in mature brain and the changes of spatial
      memory and seizure susceptibility in adult rats. METHODS: Thirty-two of 7-day-old
      (P7) Sprague-Dawley rats were divided randomly into two groups: the control group
      and the seizure group. Seizures were induced by inhalant flurothyl daily for six
      consecutive days. Rats were tested for spatial memory by using the Morris water
      maze task from postnatal 61 d(P61) to P65. Seizure threshold was examined by
      intraperitoneal injection of pentylenetetrazol, and then the brains were sampled
      on P75. The expressions of GABA(A)R alpha1 and gamma2 subunits mRNA and protein
      in cerebral cortex and hippocampus were detected by reverse transcription
      polymerase chain reaction (RT-PCR) and immunohistochemistry method. RESULTS: On
      P64, the escape latencies in water maze for the rats in the seizure group were
      significantly longer than those of the control rats [(82 424+/-35 622)ms vs (40
      712+/-29 468)ms, P=0.001]. On P65, the frequency of crossing target within 120 s
      in water maze for the rats in the seizure group were significantly less than
      those of the control rats [(1.2+/-0.9) vs (3.1+/-1.3), P<0.001]. There was no
      difference in seizure threshold between the two groups on P75 [(1 487+/-662)s vs
      (1 841+/-648)s, P=0.137]. Compared to the control rats, the accumulated optical
      density (AOD) of GABA(A)R alpha1 subunit immunoreactivity in seizure rats
      decreased significantly in the parietal cortex, CA1-2 and CA4 region (P<0.05).
      The AOD of alpha1 subunit protein immunoreactivity in the frontal cortex, CA3 and
      dentate gyrus (DG) were of no significant difference between the two groups on
      P75 (P>0.05). There were also no differences in the AOD of gamma2 subunit protein
      immunoreactivity in the parietal lobe, DG, and CA1-3 region between the two
      groups (P>0.05). The AOD of gamma2 subunit protein immunoreactivity in the
      frontal lobe and CA4 region decreased significantly in the seizure group than
      those in the control group (P<0.05). The expressions of alpha1 subunits mRNA in
      the cerebral cortex and gamma2 subunit mRNA in the hippocampus were similar
      between the two groups (P>0.05), but the expressions of alpha1 subunits mRNA in
      the hippocampus and gamma2 subunit mRNA in the cerebral cortex in the seizure
      group decreased significantly as compared with those in the control group (P<
      0.05). CONCLUSION: Recurrent seizures in neonatal rats modify GABA(A) receptor
      alpha1 and gamma2 subunits expression in the cerebral cortex and hippocampus of
      adult rats, and cause long-term cognitive deficit, Which suggests that abnormal
      GABA(A) receptor expression might play an important role in long-term cognitive
      deficit induced by early life recurrent seizures.

PMID- 17173087
TI  - [Treatment of early-stage upper and/or middle thoracic esophageal cancer with a
      new muscle-sparing thoracotomy].
AB  - OBJECTIVE: To evaluate the feasibility of performing muscle-sparing thoracotomy
      and intercostal sutures in the treatment of upper and/or middle thoracic
      esophageal cancer for the purpose of tumor control and postoperative quality of
      life improvement. METHODS: Seven patients with esophageal cancer were treated
      with vertical muscle-sparing thoracotomy and Mckeown esophagectomy. Detailed
      clinic data were summarized and analyzed with patient follow-up information.
      RESULTS: Of the 7 patients, five were still alive with a 71.4% five-year survival
      rate. There were no deaths resulting from the operation in this group. The mean
      length of thoracic incision was 11 cm. The range of hospital stays was 14 to 25
      days, with a mean length of 18 days. No patients complained of impaired shoulder
      action, and the incision pain was hardly perceived without external stimulation 1
      month after operation. CONCLUSION: Performing the muscle-sparing thoracotomy in
      the treatment of early-stage esophageal cancer located in the upper and /or
      middle thoracic segment yields a satisfactory long-term survival rate with an
      improved life quality in terms of incision pain relief and shoulder function.

PMID- 17173088
TI  - [Effect of extracellular zinc on osteoclastic resorption in dental mineralized
      tissues].
AB  - OBJECTIVE: To investigate the bone resorption caused by osteoclasts and
      modulating functions of zinc ion on dental slices. METHODS: Osteoclasts were
      separated from long-limb bones of neonatal rabbits, cultured with de-activated
      human tooth slices and glass slices. The cells in the experiment group were
      treated with 1x10(-14)mol/L-1x10(-4)mol/L zinc+10% (volume fraction) fetal calf
      serum (FCS)+alphaMEM, while those in the control group were grown in
      10%FCS+alphaMEM. Osteoclasts on glass slices were stained by TRAP staining. The
      absorption pits on tooth slices were observed by inverted phase contrast
      microscope. The resorbing activity was evaluated with the concentration of
      calcium in the supernatant liquid of osteoclasts. The ratio between the
      concentration of calcium in the experiment group and that of the control group
      was termed the resorption index. RESULTS: The isolated cells were multinuclear
      and showed positive in cytoplasma by TRAP staining. Usually, osteoclasts resorbed
      tooth slices first on the cementum and dentin, which had lower content of
      mineralized tissue. Compared with those on bone slices, the lacunae on the dental
      slices appeared less in amount, less in area and shallower in depth. They often
      showed shallow pits in a large area. Microscopy showed that the number and area
      of absorption pits formed on treated tissues were less than those on the control
      tissues. The content of calcium in the supernatant liquid increased at the
      concentrations of 1x10(-4)-1x10(-14)mol/L zinc, especially in the group of 1x10(
      8)mol/L, 1x10(-10) mol/L, 1x10(-14)mol/L zinc on the 3rd day (P<0.05). But they
      were reversed on the 7th day, except in the group of 1x10(-14)mol/L zinc. At the
      end of culture, the resorption indexes of 1x10(-4)-1x10(-7)mol/L, 1x10(-9)mol/L,
      1x10(-12)mol/L and 1x10(-13)mol/L group were lower than 1, but those of 1x10(
      8)mol/L, 1x10(-10)mol/L, 1x10(-11)mol/L and 1x10(-14)mol/L group were higher than
      1. CONCLUSION: The effect of zinc ion on osteoclastic resorption in dental slices
      is associated with phase and dosage closely.

PMID- 17173089
TI  - [Identification of low-molecular weight prostate-specific antigen(PSA) and
      lactoferrin in the prostatic secretion of benign prostatic hyperplasia].
AB  - OBJECTIVE: To investigate the expression of low-molecular-weight PSA(lw-PSA) and
      lactoferrin in the expressed prostatic secretion (EPS) from both benign prostatic
      hyperplasia (BPH) and normal prostate. METHODS: Forty human EPS samples obtained
      from 20 BPH patients and 20 normal males were subjected to two-dimensional gel
      electrophoresis (2-DE). Mass spectrometry was performed to confirm the nature of
      the secreted proteins in EPS. RESULTS: One uniquely expressed protein in BPH was
      detected and mass spectrometry determined its nature as lw-PSA (molecular weight
      10x10(3), pI 8.5-9.3). More importantly, Western blotting analysis also revealed
      that lw-PSA detected in BPH-EPS, but was undetectable in BPH-free EPS. In
      addition, up-regulation of Lactoferrin (molecular weight 35x10(3), pI 7-7.5) in
      BPH-EPS, as compared with BPH-free EPS, was also observed. More interestingly,
      lactoferrin was absent in prostate cancer tissues. CONCLUSION: Our results
      indicate lw-PSA may be produced specifically by BPH epithelium and it has a
      potential to be used as a specific biological marker for the diagnosis of BPH. In
      addition, benign prostatic epithelium can produce more lactoferrin while prostate
      cancer tissues go without its lactoferrin secretion.

PMID- 17173091
TI  - [Application of functional magnetic resonance imaging (fMRI) in the study of
      visceral hypersensitivity of the gut].
AB  - Functional magnetic resonance imaging (fMRI) has been widely applied in many
      fields, such as neurology, psychology, etc. Recently it has also been used to
      study the visceral hypersensitivity of the gut. This review gives an overview of
      the basic principle of fMRI and its application in the visceral sensitivity of
      esophagus and rectum.

PMID- 17173090
TI  - [Application of NF-kappaB reporter and Dual-Luciferase assays in the measure of
      bioactivity of interleukin-1beta and interleukin-1 receptor antagonist].
AB  - OBJECTIVE: To develop a reporter gene system based on transient transfections
      with a NF-kappaB responsive reporter gene to detect the bioactivity of IL-1beta
      and IL-1 receptor antagonist. METHODS: NF-kappaB reporter and Dual-Luciferase
      assays were applied to measure the bioactivity of IL-1beta and IL-1 receptor
      antagonist in mouse EL4 cells (some subclones of EL4 cells expressed high level
      of IL-1 receptor on cell surface). pNF-kappaB-luc and pRL-TK, used as an internal
      control, were co-transfected into EL4 cells and then the IL-1beta was added.
      RESULTS: The results indicated that IL-1beta was able to induce the expression of
      this luciferase, which could be blocked by IL-1 receptor antagonist. The optimal
      dose of IL-1beta was 5 microg/L in Dual-Luciferase assay, whose bioactivity can
      be effectively inhibited by IL-1ra at 50 microg/L. CONCLUSION: We have
      established a new method to detect the bioactivity of IL-1beta and IL-1 receptor
      antagonist, which can give repeatable results.

PMID- 17173092
TI  - Human fertility protein PUMILIO2 interacts in vitro with testis mRNA encoding
      Cdc42 effector 3 (CEP3).
AB  - PUMILIO protein regulates translation of specific mRNAs in morphogenesis and in
      development of the germ-line of model organisms such as flies and worms. Given
      that a human homologue (PUMILIO2) was recently identified in the germ-line stem
      cells, the question was raised whether it regulates translation of fertility
      mRNAs similarly to Drosophila Pumilio. Here, we describe a candidate mRNA
      encoding Cdc42 effector protein 3 (CEP3), however, a function for this protein in
      reproduction has previously not been reported. We detected three CEP3 transcripts
      in the testis tissue including one which was highly expressed and testis specific
      by northern blotting. We found that CEP mRNA contains GUUGU (A) and AUUGUA (B)
      motifs (ABB) within the 3' untranslated region (3'UTR), which are also present in
      mRNA targets of Pumilio in Drosophila. Interaction of PUMILIO2 with the fragment
      of CEP3 transcript containing the ABB array was tested by mobility shift assay
      and we found that PUMILIO2 binds the 3' untranslated region of the CEP3 mRNA.
      These results support the hypothesis that CEP3 mRNA may be a target of PUMILIO2
      protein in the human male gonad and be under translational control mediated by
      specific nucleotide motifs within the 3'UTR.

PMID- 17173093
TI  - Effects of oxytocin alone and in combination with selected hypothalamic hormones
      on ACTH, beta-endorphin, LH and PRL secretion by anterior pituitary cells of
      cyclic pigs.
AB  - Oxytocin (OT) is involved in the stimulation of secretion of anterior pituitary
      hormones in females during the periovulatory and periparturient periods. In the
      present study we examined the role of OT in control of ACTH, beta-endorphin, LH
      and PRL secretion in vitro from dispersed anterior pituitary cells collected from
      gilts during the luteal (Days 10-12; n=6) and follicular (Days 18-20; n=5) phases
      of the estrous cycle. Isolated anterior pituitary cells (1 x 10(6)/ml) were
      transferred into 24-well plates, separately for each animal, and were pre
      incubated for three days at 37 degrees C in atmosphere of 5% CO(2) and 95% air.
      The cells which attached to the dishes were incubated (3.5 h, 37 degrees C) in
      McCoy's medium in the absence (control) or in the presence of the following
      factors: CRH alone (10(-10), 10(-9), 10(-8), 10(-7) M), OT alone (10(-8), 10(-7),
      10(-6) M), LVP alone (10(-7) M), OT (10(-7) M) plus CRH (10(-9) M) and LVP (10(
      7) M) plus CRH (10(-9) M) for studying ACTH and beta-endorphin secretion; OT
      alone (10(-8), 10(-7), 10(-6) M), GnRH alone (100 ng/ml), CRH alone (10(-9) M),
      OT (10(-7) M) plus GnRH (100 ng/ml) and OT (10(-7) M) plus CRH (10(-9) M) for
      studying LH and PRL secretion. Concentrations of the studied hormones in media
      were analyzed by RIA. Oxytocin alone increased ACTH (at doses 10(-7), 10(-6) M),
      beta-endorphin (at dose 10(-8) M), LH (at dose 10(-8) M) and PRL (at doses 10(
      7), 10(-6) M) secretion by pituitary cells isolated only from luteal-phase gilts.
      None of the studied hormone concentrations in the medium was increased in
      response to OT when pituitary cells of follicular-phase gilts were examined.
      Oxytocin in combination with CRH exerted an additive effect on beta-endorphin
      secretion during the luteal phase. Summarizing, in the present study the
      stimulatory effect of oxytocin on ACTH, beta-endorphin, LH and PRL secretion by
      pituitary cells isolated from gilts during the luteal phase was demonstrated.
      However, the cells collected from follicular-phase gilts appeared to be
      unresponsive to OT. Moreover, interaction between OT and CRH in affecting beta
      endorphin secretion was shown. These results suggest that OT may be transiently
      involved in the modulation of anterior pituitary hormone secretion in cyclic
      pigs.

PMID- 17173094
TI  - Age, reproduction and fecundity of the spined loach Cobitis taenia L. (Pisces,
      Cobitidae) from Lake Klawoj (Poland).
AB  - This is the first study concerning the features of the reproduction process of
      the karyologically identified spined loach C. taenia (2n=48). The histology of 71
      ovaries, and gonadosomatic index (GSI) of karyologically identified spined loach
      Cobitis taenia L. from Lake Klawoj (Northern Poland) were examined. The absolute
      and relative fecundity of 25 females was estimated by gravimetric method. The age
      of fish was determined according to the annual increments of otholits. The
      spawning of C. taenia from Lake Klawoj took place from May to July, at a water
      temperature exceeding 18.5 degrees C. The GSI values at the beginning of the
      reproduction period ranged from 7 to 19%. The average absolute fecundity of
      females was 2078 eggs, with the number ranging from 869 to 3371 eggs. High
      individual variability in the gonad histology and the GSI values during the
      reproductive period was observed. Such variability could be the result of
      beginning the reproduction process in the fish at various times and, probably,
      due to the various numbers of batches laid and various numbers of eggs per batch.

PMID- 17173095
TI  - Retrograde transfer of testosterone to the porcine ovary in follicular and luteal
      phase of the estrous cycle in vivo.
AB  - This study was designed to determine the efficiency and rate of testosterone (T)
      retrograde transfer during the follicular and luteal phase of the estrous cycle
      in gilts (n=27). The efficiency and the rate of the retrograde transfer of T from
      the ovarian effluent into blood supplying the ovary were determined for the first
      time under in vivo conditions. Ovarian arterial blood concentration of T was
      higher than that in systemic blood during both, the follicular phase (p<0.01) and
      luteal phase (p<0.0001). The efficiency of the retrograde transfer of T into
      ovarian arterial blood was not dependent on concentration of testosterone in the
      ovarian venous blood. However, the efficiency and the rate of the retrograde
      transfer of T differed between phases of the estrous cycle. The presented results
      suggest that local retrograde transfer enriched the porcine ovary with an
      additional amount of T which may affect the ovarian secretory function.

PMID- 17173096
TI  - Oogenesis in pig ovaries during the prenatal period: ultrastructure and
      morphometry.
AB  - Oogenesis in fetal pig ovaries comprises the successive changes from the
      primordial germ cells to the dictyotene oocytes in primordial ovarian follicles.
      In this study the observations were carried out with an electron microscope and
      stereological analysis was performed. At the ultrastructural level there are no
      differences between the primordial germ cells and oogonia, but oogonia are
      connected with the intercellular bridges. The onset of the dictyotene phase was
      accompanied by the changes in the cytoplasm of oocytes. Near the nucleus, the
      yolk nucleus is formed containing numerous Golgi bodies, endoplasmic reticulum
      (ER), mitochondria and granules. ER proliferates in contact with the external
      leaflet of the nuclear envelope forming the narrow ER cisterns. Between the
      nuclear envelope and ER cisterns, the vesicles with grey content are visible. The
      proliferating ER forms numerous concentric cisterns around the nucleus. Next, the
      most external cisterns fragment, detach, and then form the cup-like structures.
      These structures separate the distinct areas of cytoplasm-compartments, which
      contain mitochondria, ribosomes and lipid droplets. The cells of cortical sex
      cords of the ovary, which encloses the oocyte, form the follicles. The volume of
      oocytes in forming follicle increases due to the increase in the number of the
      cell inclusions: lipid droplets, vacuoles and yolk globules. In the oocytes of
      primordial ovarian follicles, the compartments are transformed into the yolk
      globules, which are encountered by a sheath of ER cisterns and the grey vesicles;
      they contain the mitochondria, lipid droplets and light vacuoles. The role of the
      compartments and yolk globules as metabolic units is discussed in comparison with
      similar structures of the mature eggs of pigs and other mammal species.

PMID- 17173097
TI  - Song types and their structural features are associated with specific contexts in
      the banded wren.
AB  - We studied the use of song types and their acoustic features in different social
      contexts in the banded wren (Thryothorus pleurostictus), a resident tropical
      songbird in which males possess about 20 distinctive song types varying in
      duration, bandwidth, note composition, and trill structure. We recorded six focal
      males intensively for four days each while we observed context information such
      as during versus after dawn chorus, presence of the female, counter-versus solo
      singing, location at the edge versus centre of the territory, and proximity to
      the nest. All males used at least some song types differentially during each of
      these pairs of alternative contexts. Males also preferentially used the song
      types they shared with a given neighbour when interacting with that bird. Songs
      delivered during dawn chorus were significantly longer, wider in bandwidth, often
      compound (double songs), and more likely to contain a rattle or buzz and an up
      sweeping trill, compared to songs delivered after dawn chorus. Similar features
      were also more commonly observed when birds were engaged in intense male-male
      interactions and boundary disputes after dawn chorus, especially when
      countersinging at the edge of the territory. The presence of the female caused
      the male to deliver song types with narrower whole-song and trill bandwidth and
      fewer rattles and buzzes, and song-type diversity and fraction of compound songs
      were higher when the female was present. Thus, in addition to using type matching
      and variations in song-type switching and diversity to signal different levels of
      aggressive intention, male banded wrens also select song types based on their
      acoustic structure in different social contexts.

PMID- 17173098
TI  - Safety and efficacy of the potassium-titanyl-phosphate laser and photoselective
      vaporization of the prostate for benign prostatic hyperplasia.
AB  - The currently commercially available 80-W potassium-titanyl-phosphate laser used
      for photoselective vaporization of the prostate in men with lower urinary tract
      symptoms and benign prostatic hyperplasia (BPH) is a safe and effective
      therapeutic alternative for a wide spectrum of prostate sizes and configurations.
      Efficacy data from multicenter prospective studies, comparative studies against
      other interventions, and single-center long-term outcomes suggest the efficacy to
      be at least equivalent to that of transurethral resection of the prostate, with a
      very good safety profile. New technological developments promise to further
      enhance the utility of this laser for application in BPH and urology.

PMID- 17173100
TI  - Expanding the role of photoselective vaporization of the prostate.
AB  - The use of the potassium-titanyl-phosphate (KTP) laser for the ablative treatment
      of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH)
      has gained wide acceptance in the urologic community. The efficacy and safety of
      photoselective vaporization of the prostate using 60-W or 80-W KTP have been
      demonstrated in multiple trials, with significant impact on special high-risk
      surgical populations (ie, patients with large prostates and anticoagulated
      patients with multiple comorbidities) with symptomatic BPH. The high-power KTP
      laser technique has also shown encouraging results in the management of urethral
      strictures. With catheter removal, improvement in voiding may not immediately
      occur; however, with the efficient vaporization and limited coagulation necrosis
      that are routinely noted with high-power KTP applications, improvement may occur
      in as early as a few days to 1 week. Because of the superior surgical hemostasis
      associated with laser prostatectomy, no restrictions on physical activity are
      required after the procedure, even in the immediate postoperative period.

PMID- 17173099
TI  - The Next Generation in Laser Treatments and the Role of the GreenLight High
      Performance System Laser.
AB  - Lasers have evolved over the past decade, with technical refinements that have
      resulted in a procedure that can achieve transurethral-like results in a safe and
      efficacious manner. The physics and characteristics of the laser light, such as
      wavelength and power densities, influence efficiency of treatment and safety
      profiles of various laser techniques and systems. The currently commercially
      available 80-W potassium-titanyl-phosphate laser used for photoselective
      vaporization of the prostate gland in men with lower urinary tract symptoms and
      benign prostatic hyperplasia has been shown to be a safe and effective
      therapeutic alternative for a wide spectrum of prostate sizes and configurations.
      Refinements based on clinical experience as well as progress in available
      technologies have produced an advanced system with improvements in beam quality
      and an increase in power to provide an increase in vaporization efficiency and
      flexibility in technique. The refinements require adjustments to current
      technique. The advanced technological developments enhance the utility of this
      laser for application in benign prostatic hyperplasia and urology.

PMID- 17173101
TI  - Economic impact of surgical intervention in the treatment of benign prostatic
      hyperplasia.
AB  - The economic burden of benign prostatic hyperplasia (BPH) on our health care
      system is significant and likely to continue to grow given the burgeoning elderly
      population. Coincident with the rising number of annual physician office visits
      and expenditures for BPH has been a dramatic shift in the disease's management,
      from surgical to medical care. However, long-term cost data call into question
      the appropriateness of medical therapy as the initial treatment approach for all
      men with BPH, particularly those with moderate to severe symptoms. Although there
      has been a paradigm shift away from traditional BPH surgery, there has been
      renewed interest in the treatment of BPH with novel surgical techniques and
      minimally invasive surgeries. The economics of surgical interventions for BPH are
      discussed.

PMID- 17173102
TI  - eCAM: On To Year 4.

PMID- 17173103
TI  - Immunology and homeopathy. 4. Clinical studies-part 2.
AB  - The clinical studies on the effectiveness of homeopathy in respiratory allergy
      (18 randomized trials and 9 observational studies) are described. The literature
      of common immunologic disorders including also upper respiratory tract infections
      (URTI) and otorhinolaryngology (reported in part 1), is evaluated and discussed.
      Most of initial evidence-based research was addressed to the question of whether
      homeopathic high dilutions are placebos or possess specific effects, but this
      question has been often equivocal and is still a matter of debate. The evidence
      demonstrates that in some conditions homeopathy shows significant promise, e.g.
      Galphimia glauca (low dilutions/potencies) in allergic oculorhinitis, classical
      individualized homeopathy in otitis and possibly in asthma and allergic
      complaints, and a few low-potency homeopathic complexes in sinusitis and
      rhinoconjunctivitis. A general weakness of evidence derives from lack of
      independent confirmation of reported trials and from presence of conflicting
      results, as in case of homeopathic immunotherapy and of classical homeopathy for
      URTI. The suitable methods to evaluate homeopathy effectiveness, without altering
      the setting of cure, are also analyzed.

PMID- 17173104
TI  - Evidence-Based Research in Complementary and Alternative Medicine III: Treatment
      of Patients with Alzheimer's Disease.
AB  - This paper presents the novel domain of evidence-based research (EBR) in the
      treatment of patients with Alzheimer's disease (AD) from the perspective of
      traditional medicine and of complementary and alternative medicine. In earlier
      lectures we have described the process of evidence-based medicine as a
      methodological approach to clinical practice that is directed to aid clinical
      decision-making. Here, we present a practical example of this approach with
      respect to traditional pharmacological interventions and to complementary and
      alternative treatments for patients with AD.

PMID- 17173105
TI  - Cost-effectiveness of complementary therapies in the United kingdom-a systematic
      review.
AB  - OBJECTIVES: The aim of this review is to systematically summarize and assess all
      prospective, controlled, cost-effectiveness studies of complementary therapies
      carried out in the UK. DATA SOURCES: Medline (via PubMed), Embase, CINAHL, Amed
      (Alternative and Allied Medicine Database, British Library Medical Information
      Centre), The Cochrane Library, National Health Service Economic Evaluation
      Database (via Cochrane) and Health Technology Assessments up to October 2005.
      REVIEW METHODS: Articles describing prospective, controlled, cost-effectiveness
      studies of any type of complementary therapy for any medical condition carried
      out in the UK were included. Data extracted included the main outcomes for health
      benefit and cost. These data were extracted independently by two authors,
      described narratively and also presented as a table. RESULTS: Six cost
      effectiveness studies of complementary medicine in the UK were identified: four
      different types of spinal manipulation for back pain, one type of acupuncture for
      chronic headache and one type of acupuncture for chronic back pain. Four of the
      six studies compared the complementary therapy with usual conventional treatment
      in pragmatic, randomized clinical trials without sham or placebo arms. Main
      outcome measures of effectiveness favored the complementary therapies but in the
      case of spinal manipulation (four studies) and acupuncture (one study) for back
      pain, effect sizes were small and of uncertain clinical relevance. The same four
      studies included a cost-utility analyses in which the incremental cost per
      quality adjusted life year (QALY) was less than pound10 000. The complementary
      therapy represented an additional health care cost in five of the six studies.
      CONCLUSIONS: Prospective, controlled, cost-effectiveness studies of complementary
      therapies have been carried out in the UK only for spinal manipulation (four
      studies) and acupuncture (two studies). The limited data available indicate that
      the use of these therapies usually represents an additional cost to conventional
      treatment. Estimates of the incremental cost of achieving improvements in quality
      of life compare favorably with other treatments approved for use in the National
      Health Service. Because the specific efficacy of the complementary therapies for
      these indications remains uncertain, and the studies did not include sham
      controls, the estimates obtained may represent the cost-effectiveness non
      specific effects associated with the complementary therapies.

PMID- 17173106
TI  - Safety of traditional arab herbal medicine.
AB  - Herbal remedies are widely used for the treatment and prevention of various
      diseases and often contain highly active pharmacological compounds. Many
      medicinal herbs and pharmaceutical drugs are therapeutic at one dose and toxic at
      another. Toxicity related to traditional medicines is becoming more widely
      recognized as these remedies become popular in the Mediterranean region as well
      as worldwide. Most reports concerning the toxic effects of herbal medicines are
      associated with hepatotoxicity although reports of other toxic effects including
      kidney, nervous system, blood, cardiovascular and dermatologic effects,
      mutagenicity and carcinogenicity have also been published in the medical
      literature. This article presents a systematic review on safety of traditional
      Arab medicine and the contribution of Arab scholars to toxicology. Use of modern
      cell biological, biochemical, in vitro and in vivo techniques for the evaluation
      of medicinal plants safety is also discussed.

PMID- 17173107
TI  - The use of herbal medicine in Alzheimer's disease-a systematic review.
AB  - The treatments of choice in Alzheimer's disease (AD) are cholinesterase
      inhibitors and NMDA-receptor antagonists, although doubts remain about the
      therapeutic effectiveness of these drugs. Herbal medicine products have been used
      in the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD) but
      with various responses. The objective of this article was to review evidences
      from controlled studies in order to determine whether herbs can be useful in the
      treatment of cognitive disorders in the elderly. Randomized controlled studies
      assessing AD in individuals older than 65 years were identified through searches
      of MEDLINE, LILACS, Cochrane Library, dissertation Abstract (USA), ADEAR
      (Alzheimer's Disease Clinical Trials Database), National Research Register,
      Current Controlled trials, Centerwatch Trials Database and PsychINFO Journal
      Articles. The search combined the terms Alzheimer disease, dementia, cognition
      disorders, Herbal, Phytotherapy. The crossover results were evaluated by the
      Jadad's measurement scale. The systematic review identified two herbs and herbal
      formulations with therapeutic effects for the treatment of AD: Melissa
      officinalis, Salvia officinalis and Yi-Gan San and BDW (Ba Wei Di Huang Wan).
      Ginkgo biloba was identified in a meta-analysis study. All five herbs are useful
      for cognitive impairment of AD. M. officinalis and Yi-Gan San are also useful in
      agitation, for they have sedative effects. These herbs and formulations have
      demonstrated good therapeutic effectiveness but these results need to be compared
      with those of traditional drugs. Further large multicenter studies should be
      conducted in order to test the cost-effectiveness of these herbs for AD and the
      impact in the control of cognitive deterioration.

PMID- 17173109
TI  - Stimulating effect of Japanese herbal (kampo) medicine, hochuekkito on upper
      respiratory mucosal immune system.
AB  - Japanese herbal (Kampo) medicine, Hochuekkito (Bu-Zhong-Yi-Qi-Tang in Chinese, TJ
      41) and Juzentaihoto (Shi-Quan-Da-Bu-Tang in Chinese, TJ-48) are well-known Kampo
      formulas used as tonic. Although these medicines have separately been applied to
      the patients clinically depending on their symptoms, the differences of the
      pharmacological activities for these medicines have not been fully understood. TJ
      48 and TJ-41 were compared for their effects on antibody response in upper
      respiratory mucosal immune system in vivo. Oral administration of TJ-41 (100 mg
      kg(-1) per day) to early aged BALB/c mice, which were nasally sensitized with
      influenza hemagglutinin vaccine, significantly enhanced influenza virus-specific
      IgA and IgG antibody titers in nasal cavity and sera, respectively. However, oral
      administration of TJ-48 (100 mg kg(-1) per day) failed to show the enhancing
      activity. TJ-41 increased not only influenza virus-specific IgA antibody titer
      but also total IgA antibody titer in nasal cavity. The stimulating activity of TJ
      41 disappeared after treatment with methotrexate. The present study strongly
      suggests that TJ-41 can stimulate the mucosal immune system of upper respiratory
      tract, and results in enhancement of antigen-specific antibody response in upper
      respiratory mucosal and systemic immune systems.

PMID- 17173108
TI  - DNA microarrays in herbal drug research.
AB  - Natural products are gaining increased applications in drug discovery and
      development. Being chemically diverse they are able to modulate several targets
      simultaneously in a complex system. Analysis of gene expression becomes necessary
      for better understanding of molecular mechanisms. Conventional strategies for
      expression profiling are optimized for single gene analysis. DNA microarrays
      serve as suitable high throughput tool for simultaneous analysis of multiple
      genes. Major practical applicability of DNA microarrays remains in DNA mutation
      and polymorphism analysis. This review highlights applications of DNA microarrays
      in pharmacodynamics, pharmacogenomics, toxicogenomics and quality control of
      herbal drugs and extracts.

PMID- 17173110
TI  - Antioxidant Activity of Iranian Echium amoenum Fisch & C.A. Mey Flower Decoction
      in Humans: A cross-sectional Before/After Clinical Trial.
AB  - Medicinal plants are recognized as sources of natural antioxidants that can
      protect from biological system oxidative stress. The present cross-sectional
      before/after clinical trial was carried out to investigate the antioxidant
      properties of the decoction of the flowers of Echium amoenum Fisch & C.A. Mey in
      humans. A group of 38 healthy subjects was invited to use the E. amoenum (7 mg
      kg(-1)) twice daily for 14 days. Blood samples before and after entering the
      study were measured for lipid peroxidation level (LPO), total antioxidant
      capacity (TAC) and total thiol (SH) molecules. A significant reduction of blood
      LPO (24.65 +/- 11.3 versus 19.05 +/- 9.7, P = 0.029) was observed after 14 days
      of E. amoenum consumption. Blood TAC (1.46 +/- 0.51 versus 1.70 +/- 0.36, P =
      0.018) and total thiol molecules (0.49 +/- 0.11 versus 0.56 +/- 0.12, P = 0.001)
      increased after 14 days of E. amoenum consumption. In conclusion, this
      antioxidative stress potential of E. amoenum may be due to its bioactive
      antioxidant components, especially rosmarinic acid and flavonoids. In recent
      years the importance of oxidative stress in the pathophysiology of many human
      disorders has been confirmed, thus use of this plant as a dietary supplement is
      highly recommended.

PMID- 17173111
TI  - Ki-energy (life-energy) protects isolated rat liver mitochondria from oxidative
      injury.
AB  - We investigated whether 'Ki-energy' (life-energy) has beneficial effects on
      mitochondria. The paradigm we developed was to keep isolated rat liver
      mitochondria in conditions in which they undergo heat deterioration (39 degrees C
      for 10 min). After the heat treatment, the respiration of the mitochondria was
      measured using a Clarke-type oxygen electrode. Then, the respiratory control
      ratio (RC ratio; the ratio between State-3 and State-4 respiration, which is
      known to represent the integrity and intactness of isolated mitochondria) was
      calculated. Without the heat treatment, the RC ratio was >5 for NADH-linked
      respiration (with glutamate plus malate as substrates). The RC ratio decreased to
      1.86-4.36 by the incubation at 39 degrees C for 10 min. However, when Ki-energy
      was applied by a Japanese Ki-expert during the heat treatment, the ratio was
      improved to 2.24-5.23. We used five preparations from five different rats, and
      the significance of the differences of each experiment was either P < 0.05 or P <
      0.01 (n = 3-5). We analyzed the degree of lipid peroxidation in the mitochondria
      by measuring the amount of TBARS (thiobarbituric acid reactive substances). The
      amount of TBARS in heat-treated, no Ki-exposed mitochondria was greater than that
      of the control (no heat-treated, no Ki-exposed). However, the amount was reduced
      in the heat-treated, Ki-exposed mitochondria (two experiments; both P < 0.05)
      suggesting that Ki-energy protected mitochondria from oxidative stress. Calcium
      ions may play an important role in the protection by Ki-energy. Data also suggest
      that the observed Ki-effect involves, at least, near-infrared radiation (0.8-2.7
      mum) from the human body.

PMID- 17173112
TI  - Ichthyotherapy as alternative treatment for patients with psoriasis: a pilot
      study.
AB  - Ichthyotherapy (therapy with the so-called 'Doctorfish of Kangal', Garra rufa)
      has been shown to be effective in patients with psoriasis in the Kangal hot
      springs in Turkey. This study evaluates the efficacy and safety of ichthyotherapy
      in combination with short-term ultraviolet A sunbed radiation in the treatment of
      psoriasis under controlled conditions. We retrospectively analyzed 67 patients
      diagnosed with psoriasis who underwent 3 weeks of ichthyotherapy at an outpatient
      treatment facility in Lower Austria between 2002 and 2004. Main outcome measures
      are as follows: overall relative reduction in Psoriasis Area Severity Index
      (PASI) score; proportion of patients with an improvement in their PASI score of
      >/=75% (PASI-75) and >/=50% (PASI-50); patient-reported outcomes assessed with a
      custom questionnaire; and patient follow-up with a questionnaire sent out in
      March 2005. Safety was evaluated by reviewing adverse events and vital signs.
      Overall there was a 71.7% reduction in PASI score compared to baseline (P <
      0.0001). Of the 67 patients studied, 31 (46.3%) achieved PASI-75 and 61 patients
      (91%) achieved at least PASI-50. Patients reported substantial satisfaction with
      the treatment. The reported mean remission period was 8.58 months [95% confidence
      interval (CI) 6.05-11.11]. A total of 87.5% of patients reported a more favorable
      outcome with ichthyotherapy, when asked to compare ichthyotherapy to other
      previously tried therapies. Sixty-five percent stated that after the relapse
      their symptoms were less severe than before treatment. There were no significant
      adverse events. The benefit demonstrated in this study along with the favorable
      safety profile suggests that ichthyotherapy could provide a viable treatment
      option for patients with psoriasis.

PMID- 17173113
TI  - Cold Therapy in Migraine Patients: Open-label, Non-controlled, Pilot Study.
AB  - Some patients with headache report that they have frequently used physical
      therapies such as application of cold to relieve their headache. There are only a
      few reported studies related to cold therapies in patients with migraine. In this
      study, we investigated the effect of cold application on migraine patients.
      Twenty-eight migraine patients were included. Cold therapy was administered to
      them by gel cap. Patients used this cap during their two migraine attacks. Before
      and after the cold therapy, headache severity was recorded by using visual
      analogue scale (VAS). Patients used this cap for 25 min in each application. They
      recorded their VAS score just after the therapy and 25 min, 1 h, 2 h and 3 h
      later. Two patients could not use this therapy due to side effects (one due to
      cold intolerance and one due to vertigo) in both applications. Therefore,
      therapeutic efficacy was evaluated in 26 patients. Twenty-five minutes after
      treatment of the first attack, VAS score was decreased from 7.89 +/- 1.93 to 5.54
      +/- 2.96 (P < 0.01). Twenty-five minutes after treatment of the second attack,
      VAS score was decreased from 7.7 +/- 1.8 to 5.4 +/- 3.55 (P < 0.01). Cold
      application alone may be effective in some patients suffering from migraine
      attacks. Its combination with conventional drugs should be investigated in future
      studies.

PMID- 17173114
TI  - Physicians' attitudes toward complementary and alternative medicine and their
      knowledge of specific therapies: a survey at an academic medical center.
AB  - The purpose of this study was to evaluate the attitudes of physicians at an
      academic medical center toward complementary and alternative medicine (CAM)
      therapies and the physicians' knowledge base regarding common CAM therapies. A
      link to a Web-based survey was e-mailed to 660 internists at Mayo Clinic in
      Rochester, MN, USA. Physicians were asked about their attitudes toward CAM in
      general and their knowledge regarding specific CAM therapies. The level of
      evidence a physician would require before incorporating such therapies into
      clinical care was also assessed. Of the 233 physicians responding to the survey,
      76% had never referred a patient to a CAM practitioner. However, 44% stated that
      they would refer a patient if a CAM practitioner were available at their
      institution. Fifty-seven percent of physicians thought that incorporating CAM
      therapies would have a positive effect on patient satisfaction, and 48% believed
      that offering CAM would attract more patients. Most physicians agreed that some
      CAM therapies hold promise for the treatment of symptoms or diseases, but most of
      them were not comfortable in counseling their patients about most CAM treatments.
      Prospective, randomized controlled trials were considered the level of evidence
      required for most physicians to consider incorporating a CAM therapy into their
      practice. The results of this survey provide insight into the attitudes of
      physicians toward CAM at an academic medical center. This study highlights the
      need for educational interventions and the importance of providing physicians
      ready access to evidence-based information regarding CAM.

PMID- 17173115
TI  - Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux:
      Role of Aryl-Tetralin Lignans.
AB  - We have evaluated the effect of variation in aryl-tetralin lignans on the
      radioprotective properties of Podophyllum hexandrum. Two fractionated fractions
      of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying
      aryl-tetralin lignan content were utilized for the present study. The peroxyl ion
      scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1)
      and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h
      study, S2 exhibited significant (P < 0.05) antioxidant activity in different
      metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific
      reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug
      ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the
      formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and
      also showed 45.01% site-specific activity (1000 mug ml(-1)), along with
      significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared
      to S2. Such activities of S1 could be attributed to the significantly (P < 0.05)
      higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl
      podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings
      clearly prove that aryl-tetralin lignan content influences the radiation
      protective potential of the Podophyllum fractions to a great extent.

PMID- 17173117
TI  - A Five-year Follow-up of Quality of Life in Women with Breast Cancer in
      Anthroposophic and Conventional Care.
AB  - Complementary and alternative medicine is used by many cancer patients in most
      parts of the world, and its use is increasing. The aim of the present study was
      to examine, over 5 years, the perceived quality of life/life satisfaction in two
      samples of women with breast cancer who were treated with anthroposophic care or
      conventional medical treatment only. Data from admission, after 1 year and after
      5 years are used for the comparisons. On admission to the study the women in
      anthroposophic care perceived their quality of life to be lower than that of the
      women in the conventional treatment group, especially for emotional, cognitive
      and social functioning and overall quality of life. Sixty women who actively
      chose treatment with anthroposophic medicine and 60 individually matched women
      treated with conventional medicine participated. Quality of life was measured by
      the EORTC QLQ-C30 and the Life Satisfaction Questionnaire. Twenty-six women
      within anthroposophic care and 31 women within conventional medicine survived the
      5 years. Effect size (ES) estimation favored the anthroposophic group in seven of
      the subscales mostly measuring emotional functioning. The ES for four of the
      subscales favored the conventional treatment group, mostly concerning physical
      functioning. After 5 years there were improvements in overall quality of life and
      in emotional and social functioning compared to admission for the women in
      anthroposophic care. The improvements took place between admission and 1 year,
      but not further on. Only minor improvements were found in the matching group.

PMID- 17173116
TI  - Studies of advanced stages of meditation in the tibetan buddhist and vedic
      traditions. I: a comparison of general changes.
AB  - This article is the first of two comparing findings of studies of advanced
      practitioners of Tibetan Buddhist meditation in remote regions of the Himalayas,
      with established results on long-term practitioners of the Transcendental
      Meditation programs. Many parallel levels of improvement were found, in sensory
      acuity, perceptual style and cognitive function, indicating stabilization of
      aspects of attentional awareness. Together with observed increases in EEG
      coherence and aspects of brain function, such changes are consistent with growth
      towards a state of total brain functioning, i.e. development of full mental
      potential. They are usually accompanied by improved health parameters. How they
      may be seen to be consistent with growth of enlightenment will be the subject of
      a second article.

PMID- 17173118
TI  - Johrei family healing: a pilot study.
AB  - Johrei is a form of spiritual healing comprising "energy channelling" and light
      massage given either by a trained healer or, after some basic training, by
      anyone. This pilot trial aimed to identify any potential benefits of family-based
      Johrei practice in childhood eczema and for general health and to establish the
      feasibility of a subsequent randomised controlled trial. Volunteer families of 3
      5 individuals, including at least one child with eczema were recruited to an
      uncontrolled pilot trial lasting 12 months. Parents were trained in Johrei
      healing and then practised at home with their family. Participants kept diaries
      and provided questionnaire data at baseline, 3,6 and 12 months. Eczema symptoms
      were scored at the same intervals. Scepticism about Johrei is presently an
      obstacle to recruitment and retention of a representative sample in a clinical
      trial, and to its potential use in general practice. The frequency and quality of
      practise at home by families may be insufficient to bring about the putative
      health benefits. Initial improvements in eczema symptoms and diary recorded
      illness, could not be separated from seasonal factors and other potential
      confounders. There were no improvements on other outcomes measuring general
      health and psychological wellbeing of family members.

PMID- 17173120
TI  - Complementary and alternative medicine in clinical practice. Complementary and
      allopathic medicine: the hospital as a place of possible integration: december 2
      3, 2005, conference room, s. Carlo borromeo hospital, milan.

PMID- 17173119
TI  - Improvement of Memory by Means of Ultra-Low Doses of Antibodies to S-100B
      Antigen.
AB  - Antigen S-100B of nervous tissue, according to the data of numerous studies,
      affects the mechanisms of nervous system plasticity and memory. The influence of
      ultralow doses of antibodies to S-100B (6C dilution, according to the homeopathic
      pharmacopoeia) has been studied on three learning behavioral models on Wistar
      rats, which were inhibitory avoidance, choosing of bowls with sucrose and feeding
      behavior cessation after auditory signal. For all three tasks, parameters of
      reproduction of the learned skills improved after per oral administration of
      potentiated antibodies to S-100B antigen immediately after learning. Possible
      mechanisms of the anti-S-100B antibodies influence on memory formation are
      discussed.

PMID- 17173122
TI  - Evidence-based Complementary and Alternative Medicine.

PMID- 17173121
TI  - What is qi?

PMID- 17173138
TI  - IFN-gamma stimulates osteoclast formation and bone loss in vivo via antigen
      driven T cell activation.
AB  - T cell-produced cytokines play a pivotal role in the bone loss caused by
      inflammation, infection, and estrogen deficiency. IFN-gamma is a major product of
      activated T helper cells that can function as a pro- or antiresorptive cytokine,
      but the reason why IFN-gamma has variable effects in bone is unknown. Here we
      show that IFN-gamma blunts osteoclast formation through direct targeting of
      osteoclast precursors but indirectly stimulates osteoclast formation and promotes
      bone resorption by stimulating antigen-dependent T cell activation and T cell
      secretion of the osteoclastogenic factors RANKL and TNF-alpha. Analysis of the in
      vivo effects of IFN-gamma in 3 mouse models of bone loss - ovariectomy, LPS
      injection, and inflammation via silencing of TGF-beta signaling in T cells -
      reveals that the net effect of IFN-gamma in these conditions is that of
      stimulating bone resorption and bone loss. In summary, IFN-gamma has both direct
      anti-osteoclastogenic and indirect pro-osteoclastogenic properties in vivo. Under
      conditions of estrogen deficiency, infection, and inflammation, the net balance
      of these 2 opposing forces is biased toward bone resorption. Inhibition of IFN
      gamma signaling may thus represent a novel strategy to simultaneously reduce
      inflammation and bone loss in common forms of osteoporosis.

PMID- 17173142
TI  - The invention of blue and purple pigments in ancient times.
AB  - This tutorial review examines manmade blue and purple pigments appearing in
      antiquity. They were obtained by chemical synthesis from mineral starting
      materials and refer to chemical compounds: Egyptian Blue (CaCuSi4O10), Han Blue
      (BaCuSi4O10) and Han Purple (BaCuSi2O6), Maya Blue
      (x.indigo.(Mg,Al)4Si8(O,OH,H2O)24) and Ultramarine Blue (Na,Ca)8(AlSiO12)(S,
      SO4,Cl). The Egyptian and Chinese copper-based pigments are assumed to have been
      developed independently and are presumably an outcome of the historical
      developments in glazing techniques. A technology transfer from Egypt into China
      cannot be fully excluded but, based on the facts acquired up to now, looks less
      probable.

PMID- 17173139
TI  - A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular
      carcinoma treatment.
AB  - The forkhead box m1 (Foxm1) transcription factor is essential for initiation of
      carcinogen-induced liver tumors; however, whether FoxM1 constitutes a therapeutic
      target for liver cancer treatment remains unknown. In this study, we used
      diethylnitrosamine/phenobarbital treatment to induce hepatocellular carcinomas
      (HCCs) in either WT mice or Arf(-/-)Rosa26-FoxM1b Tg mice, in which forkhead box
      M1b (FoxM1b) is overexpressed and alternative reading frame (ARF) inhibition of
      FoxM1 transcriptional activity is eliminated. To pharmacologically reduce FoxM1
      activity in HCCs, we subjected these HCC-bearing mice to daily injections of a
      cell-penetrating ARF(26-44) peptide inhibitor of FoxM1 function. After 4 weeks of
      this treatment, HCC regions displayed reduced tumor cell proliferation and
      angiogenesis and a significant increase in apoptosis within the HCC region but
      not in the adjacent normal liver tissue. ARF peptide treatment also induced
      apoptosis of several distinct human hepatoma cell lines, which correlated with
      reduced protein levels of the mitotic regulatory genes encoding polo-like kinase
      1, aurora B kinase, and survivin, all of which are transcriptional targets of
      FoxM1 that are highly expressed in cancer cells and function to prevent
      apoptosis. These studies indicate that ARF peptide treatment is an effective
      therapeutic approach to limit proliferation and induce apoptosis of liver cancer
      cells in vivo.

PMID- 17173140
TI  - Oxidative stress mediates tau-induced neurodegeneration in Drosophila.
AB  - Markers of oxidative damage have been detected in brain tissue from patients with
      Alzheimer disease (AD) and other neurodegenerative disorders. These findings
      implicate oxidative injury in the neurodegenerative process, but whether
      oxidative stress is a cause or a consequence of neurotoxicity remains unclear. We
      used a Drosophila model of human tauopathies to investigate the role of oxidative
      stress in neurodegeneration. Genetic and pharmacological manipulation of
      antioxidant defense mechanisms significantly modified neurodegeneration in our
      model, suggesting that oxidative stress plays a causal role in neurotoxicity. We
      demonstrate that the JNK signaling pathway is activated in our model, which is in
      agreement with previous findings in AD tissue. Furthermore, we show that the
      extent of JNK activation correlates with the degree of tau-induced
      neurodegeneration. Finally, our findings suggest that oxidative stress acts not
      to promote tau phosphorylation, but to enhance tau-induced cell cycle activation.
      In summary, our study identifies oxidative stress as a causal factor in tau
      induced neurodegeneration in Drosophila.

PMID- 17173143
TI  - The long and winding road to the structure of homo-DNA.
AB  - Homo-DNA ((4'-->6')-linked oligo-2',3'-dideoxy-beta-D-glucopyranose nucleic acid)
      constitutes the earliest synthetic model system whose pairing properties have
      been studied within an etiology of nucleic acid structure. Its conception as part
      of a program directed at a rationalization of Nature's selection of pentoses over
      other candidates as the carbohydrate building block in the genetic material was
      motivated by the question: why pentose and not hexose? Homo-DNA forms an
      autonomous pairing system and its duplexes are entropically stabilized relative
      to DNA duplexes. Moreover, the base pairing priorities in homo-DNA duplexes
      differ from those in DNA. A deeper understanding of the particular properties of
      homo-DNA requires knowledge of its structure. Although diffraction data for
      crystals of a homo-DNA octamer duplex were available to medium resolution in the
      mid-1990s, it took another decade for the structure to be solved. In this
      tutorial Review we describe the odyssey from the crystallization to the final
      structure determination with its many failures and disappointments and the
      development of selenium chemistry to derivatize nucleic acids for
      crystallographic phasing. More than fifty years after the discovery of the DNA
      double helix, the story of homo-DNA also provides a demonstration of the limits
      of theoretical models and offers a fresh view of fundamental issues in regard to
      the natural nucleic acids, such as the origins of antiparallel pairing and
      helicality.

PMID- 17173144
TI  - Micropatterned supported membranes as tools for quantitative studies of the
      immunological synapse.
AB  - In living cells, membrane receptors transduce ligand binding into signals that
      initiate proliferation, specialization, and secretion of signaling molecules.
      Spatial organization of such receptors regulates signaling in several key immune
      cell interactions. In the most extensively studied of these, a T cell recognizes
      membrane-bound antigen presented by another cell, and forms a complex junction
      called the "immunological synapse" (IS). The importance of spatial organization
      at the IS and the quantification of its effect on signaling remain controversial
      topics. Researchers have successfully investigated the IS using lipid bilayers
      supported on solid substrates as model antigen-presenting membranes. Recent
      technical developments have enabled micron- and nanometre-scale patterning of
      supported lipid bilayers (SLBs) and their application to immune cell studies with
      provocative results, including spatial mutation of the IS. In this tutorial
      review, we introduce the IS; discuss SLB techniques, including micropatterning;
      and discuss various methods used to perturb and quantify the IS.

PMID- 17173145
TI  - Ring closing enyne metathesis: a powerful tool for the synthesis of heterocycles.
AB  - The ring closing metathesis (RCM) is a powerful method in organic synthesis for
      the preparation of cyclic compounds by formation of new carbon-carbon bonds. In
      the past years a particular subclass of the RCM, the ring closing enyne
      metathesis (RCEYM), has attracted attention due to its synthetic potential in the
      generation of ring structures with 1,3-diene moieties, which can subsequently be
      further functionalised. In this tutorial review mechanistic considerations will
      be described and the synthetic power of this useful and attractive carbon-carbon
      bond forming reaction will be illustrated by recent examples of RCEYM
      applications in the preparation of heterocyclic compounds.

PMID- 17173146
TI  - Transition metal-mediated P-C/X exchange at bound phosphine ligands (X=aryl,
      alkyl, NR2, OR and F): scope and mechanisms.
AB  - The range of transition metal-mediated P-C/X exchange reactions that result in
      the replacement of a phosphine substituent with another group, X, are categorised
      according to the nature of the replacing group (X=aryl or alkyl, N- and O-based
      species and fluoride). Proposed mechanisms for P-C/X exchange are described and
      the factors promoting these unusual-and often undesirable-reactions are
      discussed. This tutorial review should be of relevance for those engaged in
      homogeneous catalysis, C-F activation and the synthesis of complexes combining
      soft metal centres and hard donor ligands.

PMID- 17173147
TI  - Photo-driven molecular devices.
AB  - In this critical review, we discuss switching of the light-powered bistable
      rotaxanes and catenanes and highlight the practical applications of some of these
      systems. Photoactive molecular and supramolecular machines are comprised of two
      parts-1) a switching element, based on noncovalent interactions within the
      recognition units, which is responsible for executing mechanical movement, and 2)
      a light-harvesting unit which utilizes light to control the competitive
      interactions between the recognition sites. We also survey another class of
      molecular devices, namely molecular rotary motors--i.e., those that behave like
      their macroscopic counterparts--in which photochemically and thermally induced
      mechanical movement relies on isomerizations of a pivotal C=C bond, leading to a
      rotation of the top propeller part with respect to the stationary bottom part of
      the helical shaped chiral molecule. (146 references.).

PMID- 17173148
TI  - Structure and binding properties of water-soluble cavitands and capsules.
AB  - Synthetic receptors are modern tools for investigations into the forces involved
      in recognition. A widely exploited class of receptors are the resorcin[4]arene
      based cavitands and capsules. This critical review (71 references) describes the
      evolution of water-soluble versions of these structures, along with insights the
      resulting host-ndash complexes have provided with regard to complexation driving
      forces in water. An emphasis has been placed on the influence of host structure
      on guest affinity and dynamics.

PMID- 17173149
TI  - Polyoxometalate clusters, nanostructures and materials: from self assembly to
      designer materials and devices.
AB  - Polyoxometalates represent a diverse range of molecular clusters with an almost
      unmatched range of physical properties and the ability to form structures that
      can bridge several length scales. The new building block principles that have
      been discovered are beginning to allow the design of complex clusters with
      desired properties and structures and several structural types and novel physical
      properties are examined. In this critical review the synthetic and design
      approaches to the many polyoxometalate cluster types are presented encompassing
      all the sub-types of polyoxometalates including, isopolyoxometalates,
      heteropolyoxometalates, and reduced molybdenum blue systems. As well as the
      fundamental structure and bonding aspects, the final section is devoted to
      discussing these clusters in the context of contemporary and emerging
      interdisciplinary interests from areas as diverse as anti-viral agents,
      biological ion transport models, and materials science.

PMID- 17173151
TI  - [Quantification of the Nelson de Moraes's indicator (curve of proportional
      mortality). Revista de Saude Publica, 7:103-13, 1973].
AB  - Working with the Nelson de Moraes's indicator (curve of proportional mortality)
      it is introduced a criterion to quantify the curves, trying in this way a numeric
      value that, synthetizing the contribution of the different age groups to the
      mortality, indicates the level of health.

PMID- 17173152
TI  - [Quantification of the Nelson de Moraes's indicator (curve of proportional
      mortality)].

PMID- 17173153
TI  - [Biogeography, origin, and distribution of triatominae domiciliarity in Brazil.
      Revista de Saude Publica, 14(3):265-99, 1980].
AB  - An association is established between the Brazilian geographical pattern of the
      domiciliarity of the triatominae bugs and open lands characterized by natural
      savanna vegetation or artificial, man-made landscapes. The Brazilian open lands
      involved are the "caatingas'' and "cerrados", both wholly included in Brazilian
      territory, while the mixed Southern subtropical prairies belong to systems
      extending bevond national boundary lines. The other open lands are anthropic
      lands opened mainly by the destruction of primitive forests of the tropical
      Atlantic system. Attempts were made to subject the four synanthropic species of
      epidemiological importance to model paleoecologic refuges and endemic centers.
      Triatoma sordida, Triatoma brasiliensis, and Triatoma pseudomaculata seem to have
      their endemic centers in the "cerrados" and "caatinga", while the Panstrongylus
      megistus may have originated in the tropical Atlantic forest system. The Triatoma
      infestans, however, seem to have originated in Bolivia, then were spread to large
      dispersal regions by man. Thus it can be assumed that domiciliarity is arrived at
      through an opportunistic mechanism stimulated by shelter and food availability
      factors. Once established, domiciliarity favors the species survival and
      dispersal, and this is of particular interest to control and surveillance
      programs because it increases the probability of the triatominae's success in
      synanthropic specialization. The present intense anthropic activities in the
      Amazonian system will lead to even greater expansion into the open lands;
      consequently, a triatominae domiciliarity spread can be expected, due to either
      autochthonous or man-introduced populations. A public health problem will then
      arise in a region where it has, heretofore, been unknown.

PMID- 17173154
TI  - [A re-reading and a homage to Biogeography, origin, and distribution of
      triatominae domiciliarity in Brazil].

PMID- 17173155
TI  - [Triatominae biogeography and the European cherry trees].

PMID- 17173156
TI  - [Occupational accidents: social insurance costs and work days lost].
AB  - OBJECTIVE: To estimate the proportion of occupational accident benefits granted
      within the total for health-related social security benefits, viewing the costs
      according to benefit type and the impact on productivity according to work days
      lost. METHODS: Records of benefit decisions from the National Benefits System of
      the National Social Security Institute for the State of Bahia in 2000 were
      utilized. Occupational accidents were defined in accordance with the clinical
      diagnoses of External Causes, Injuries and Poisoning (SS-00 to T99) of the
      International Classification of Diseases, 10th Revision, and with the benefit
      type, which distinguishes between occupational and non-occupational health
      problems. RESULTS: A total of 31,096 benefits granted due to illnesses or health
      problems were studied. Of these, 2,857 (7.3%) were caused by work accidents.
      Greater proportions were found among workers in the manufacturing, construction,
      electricity and gas industries, accounting for 18% of the total benefits. The
      costs of occupational accident benefits were estimated to be R$8.5 million, with
      around half a million work days lost during the year studied. CONCLUSIONS:
      Despite the fact that these data are under-reported and are restricted to workers
      who were able to receive health-related benefits, the findings reveal that
      avoidable health problems have a major impact on productivity and on the budget
      of the National Social Security Institute, thereby reinforcing the need for their
      prevention.

PMID- 17173157
TI  - [Prevalence of voice alteration among educators and its relationship with self
      perception].
AB  - OBJECTIVE: To verify the prevalence of self-reported voice alteration among
      educators in creches, and associated factors. METHODS: This was a cross-sectional
      observational study carried out in 2001, in eight creches in the city of Sao
      Paulo at which actions within the Creche Program were being developed. This
      program formed part of the health promotion activities of a speech therapy
      investigation laboratory. The data collection was done by means of a
      questionnaire that was filled out by 93 educators, with questions on
      sociodemographic characteristics, aspects of the organization and physical
      environment of the work, habitual voice utilization, history of illnesses,
      lifestyle and perceptions regarding voice alterations. Assessment of hearing
      perception was done on the participants' voices. The statistical analysis
      utilized proportions, central trend measurements, Chi-square test with Yates
      correction and multiple logistic regression analysis. RESULTS: Eighty percent of
      the educators reported that they had voice alterations, although only 26% had
      sought treatment. A large proportion (39%) reported that they had had their
      problem for four years or more, that it was intermittent (82%) and that they had
      it to a slight or moderate degree (74%). They believed that the main cause of
      voice alteration was their use of their voices (82%), and their principal symptom
      was hoarseness (54%). Self-reported voice alteration was statistically associated
      with presence of voice alteration observed during assessment and with having had
      some guidance on voice usage. CONCLUSIONS: Adequate perception among educators
      regarding their voice problems could become an important tool for future work
      among this population with a view to diminishing the high prevalence of voice
      alteration encountered.

PMID- 17173158
TI  - [Quality of life among dentists of a local public health service].
AB  - OBJECTIVE: To assess quality of life and related factors among dentists of a
      local public health service. METHODS: A cross-sectional study was carried out
      comprising dentists working (N=237) in the city of Goiania, Midwesthern Brazil,
      in 2004. Data were collected using a questionnaire including the WHOQOL-Bref
      instrument, demographic data and occupation information, and self-rated health
      status and quality of life. Simple and multiple logistic regression analyses were
      used to estimate associations. RESULTS: Response rate was 62.9% (N=149). The
      physical domain had the highest mean scores (70.3; SD=14.6) and the environment
      domain had the lowest mean scores (59.4; SD=13.7). Most dentists had low quality
      of life in the physical (51.0%) and psychological domains (52.3%) and high
      quality of life in the social relationships (50.3%) and environment domains
      (59.1%). The multiple logistic regression showed an association between self
      rated health status and satisfaction and the physical domain; and self-rated
      quality of life and the physical, psychological and environment domains.
      CONCLUSIONS: The occupation group studied showed low quality of life in the
      physical and psychological domains and high quality of life in the social
      relationships and environment domains, which were associated to self-rated
      quality of life, current health status and satisfaction.

PMID- 17173159
TI  - [University residence halls: socialization processes and drug consumption].
AB  - OBJECTIVE: To investigate and analyze the discourse of students living in
      university residence halls regarding socialization processes and drug
      consumption. METHODS: This was qualitative research among 20 undergraduate
      students living in university residence halls in the city of Sao Paulo, Brazil,
      in 2003. Residence halls were taken to be socialization spaces for young people
      that enable the presence of low-income students at university. The interviews
      covered students' knowledge of the history of the residence hall, their
      experience of living in student residences and their perceptions regarding drug
      consumption. The methodological procedure that served as the basis for
      collection, organization and analysis of the interview data was examination of
      the collective discourse of the subjects. RESULTS: It was shown that the students
      had little knowledge of the history of the residence hall; solutions for problems
      they faced in the residence hall were sought individually; and the two main
      concepts observed among the people living there for preventing drug consumption
      were war on drugs and damage limitation. It was seen that there was a negative
      view regarding student residence halls that related to the constant publication
      of disturbing events and lack of knowledge of the importance of residence halls
      for enabling poor students to remain at university. CONCLUSIONS: In the opinion
      of the people living in student residence halls, such accommodation enables
      access to university, despite the difficulties in living together and in
      administration by the university. With regard to the use of drugs in the
      residence hall, some of the people living there emphasized the need for less
      tolerance towards drug consumption, while others stressed the importance of
      educational work, particularly among those who are just starting to live there.

PMID- 17173160
TI  - [Prevalence and risk factors of common mental disorders among medical students].
AB  - OBJECTIVE: To estimate the prevalence and assess risk factors of common mental
      disorders among medical students. METHODS: A cross-sectional study was carried
      out comprising 551 university medical students in the state of Sao Paulo,
      Southeastern Brazil. A self-administered questionnaire to collect
      sociodemographic and course-related data as well as the Self-Reporting
      Questionnaire were used. Both Chi-square test and logistic regression were used
      in data analyses. RESULTS: A total of 82.6% of the students enrolled in the
      course participated in the study. Most of them were women (61%), 60% aged between
      20 and 23 years, and 99% were from other cities. The prevalence of common mental
      disorders was 44.7% and they were independently associated with: difficulty in
      making friends (OR=2.0), poor self-evaluation of academic performance (OR=1.7),
      thoughts of dropping out of the medical course (OR=5.0) and perceived lack of
      emotional support (OR=4.6). Although prevalence of these disorders was associated
      with the course period in the first analysis, this association was not maintained
      in the multivariate analysis. CONCLUSIONS: The prevalence of common mental
      disorders was shown to be high among medical students, associated with variables
      concerning support networks. Emotionally tense experiences such as dealing with
      seriously ill patients and peer group formation in the last years of the medical
      course are potentially strong stressors, especially for those with poor social
      support. It is suggested that educational institutions should be aware of that
      and make interventions aiming at treating and caring for the students' distress.

PMID- 17173161
TI  - [Philanthropic general hospitals: a new setting for psychiatric admissions].
AB  - OBJECTIVE: To understand the process that led Brazilian philanthropic general
      hospitals to implement psychiatric units and to describe the main characteristics
      and therapeutic approaches of these services. METHODS: Ten institutions in three
      Brazilian states (Minas Gerais, Sao Paulo e Santa Catarina) were assessed in
      2002. Forty-three semi-structured interviews were carried out with health
      professionals who worked at the hospitals to collect data on service
      implementation process, therapeutic approaches and current situation. The
      interviews were audio-recorded and their content was analyzed. RESULTS: There was
      no mental hospital in the cities where the institutions were located. In five
      hospitals, psychiatric patients were admitted to general medical wards because
      there was no psychiatric unit. The therapeutic approach in six hospitals was
      based on psychopharmacological treatment. Due to lack of resources and more
      appropriate therapeutic planning, the admission of patients presenting
      psychomotor agitation increases resistance against psychiatric patients in
      general hospitals. Financial constraints regarding laboratory testing is still a
      challenge. There is no exchange between local authorities and hospital
      administrators of these institutions that are compelled to exceed the allowed
      number of admissions to meet the demand of neighboring cities. CONCLUSIONS: The
      need for mental health care to local populations combined with individual
      requests of local authorities and psychiatrists made possible the implementation
      of psychiatric units in these localities. In spite of the efforts and flexibility
      of health professional working in these institutions, there are some obstacles to
      be overcome: resistance of hospital community against psychiatric admissions,
      financial constraints, limited professional training in mental health and the
      lack of a therapeutic approach that goes beyond psychopharmacological treatment
      alone.

PMID- 17173162
TI  - [Risk factors for mortality among elderly people].
AB  - OBJECTIVE: The risk factors for diseases and premature deaths are important in
      drawing up preventive measures. This study had the aim of analyzing the risk
      factors for death among elderly people. METHODS: This study was carried out among
      participants in the SABE (Health, Wellbeing and Aging) study, in the city of Sao
      Paulo in 2000. Interviews were conducted with 2,143 elderly people (60 years old
      or over), using a standardized questionnaire for the SABE study. The sample was
      obtained from census tracts, in two stages, with replacements and with
      probability proportional to the population, and with supplementation of the
      sample of people aged 75 years or over. The final data were weighted so that they
      could be expanded. Between the two data collection times, there were 38 deaths
      which comprised study sample. Logistic regression was utilized for the data
      analysis, with a significance level of 5%. RESULTS: The risk factors found were:
      locomotion difficulty, advanced age, male gender, self-assessment of health as
      "bad" and difficulty in going to the bathroom, OR=3.15; 2.93; 2.90; 2.69 and
      2.51, respectively. CONCLUSIONS: The results may contribute towards the adoption
      of preventive measures for elderly people, with the aim of diminishing the
      expected number of fatal outcomes.

PMID- 17173163
TI  - [Drug-related toxic events in the state of Sao Paulo, Brazil].
AB  - OBJECTIVE: To assess the epidemiological characteristics of drug-related toxic
      events in the State of Sao Paulo, Brazil. METHODS: A descriptive epidemiological
      case series study was conducted. Using the category "drug-related toxic event",
      6,673 registered cases were analyzed in the Toxicology Centers in the State of
      Sao Paulo throughout 1998. The variables studied comprised the characteristics of
      the events and the affected patients, toxic agents and the circumstances
      involved. The analysis of toxic agents took into consideration three levels of
      disaggregation: therapeutical groups, active ingredients and commercial brand
      names. RESULTS: Drugs ranked first among all toxic agents registered in the
      Centers. Drug-related toxic events were mostly reported by phone (78.5%) and
      hospitals (86.6%); they were originated from acute oral exposure (90.2%) at home
      (85.7%) in the urban area (95%). Most people affected were females (59%) in their
      first decade of life (49.4%), mainly between two and three years of age. The most
      common active ingredients found were: phenobarbital, diazepam, haloperidol,
      carbamazepine and bromazepam. The main circumstances were accidental ingestion
      (38.8%) and suicidal attempts (36.5%) and among the related active ingredients,
      the most prevailing therapeutical group were psychiatric, analgesic/anesthetic
      and respiratory. CONCLUSIONS: Law-abiding practices regarding prescription drugs
      are needed, as well as toxicological surveillance according to the National
      Health System guidelines.

PMID- 17173164
TI  - [Validity of self-reported weight and height: the Goiania study, Brazil].
AB  - OBJECTIVE: To assess the validity of self-reported weight and height at the time
      of diagnosing obesity, and to identify the sociodemographic and individual
      characteristics that might be a source of information bias. METHODS: This was a
      cross-sectional population-based study carried out in the city of Goiania in
      2001. Interviews were conducted with 1,023 individuals aged 20-64 years, in their
      homes, to collect sociodemographic and self-reported weight and height
      information. On the same occasion, weight and height measurements were made on
      these individuals. The mean differences and correlation coefficients between self
      reported and measured data were calculated according to age, body mass index
      (BMI), schooling, income and height. RESULTS: Both the men and women
      overestimated their heights (p<0.05), by 0.9 cm and 2.2 cm, respectively. There
      was no difference between self-reported and measured weights, either for the men
      (-0.44 kg; p=0.06) or for the women (-0.03 kg; p>0.05). The behavior of
      overestimating height was influenced by age, schooling, height and body mass
      index. Although this index obtained from the self-reported data was
      underestimated (p<0.05), by 0.27 kg/m(2) and 0.67 kg/m(2) for men and women
      respectively, the measured and self-reported data presented a high degree of
      agreement. Both the sensitivity and specificity of the self-reported body mass
      index were high, in relation to identifying the measured index. CONCLUSIONS: In
      epidemiological studies for monitoring the prevalence of excess weight in
      populations, self-reported weights and heights constitute reliable data, which
      gives validity to the methodology utilized.

PMID- 17173165
TI  - [Growth of full term low and adequate birth weight infants during the first two
      years of life].
AB  - OBJECTIVE: To assess the growth pattern of full term low and adequate birth
      weight infants during the first two years of life and to identify the
      determinants at the time of the greatest growth deceleration. METHODS: A
      prospective cohort study was conducted with 148 full term infants in five small
      towns of the state of Pernambuco, Northeastern Brazil. Newborns were recruited
      from maternities between January 1993 and January 1994 and their anthropometric
      measurements were taken at one, two, four, six, 12 and 24 months of life. Risk
      factors were analyzed using multivariable linear regression. RESULTS: The
      increment of mean weight-for-age and length-for-age were more evident for low
      birth weight when compared with adequate weight infants, especially during the
      first two months after birth. From this point onward it was observed a
      progressive mean growth deceleration in both indexes up to 12 months of life. All
      infants had similar weight and length growth patterns. However, adequate birth
      weight infants remained in an upper level. Socioeconomic variables explained 23%
      of variation for weight-for-age, followed by 4% for birth weight. Socioeconomic
      condition was also the factor mostly affecting length-for-age, explaining 28% of
      its variation, followed by birth weight, maternal height and diarrhea.
      CONCLUSIONS: The study results suggest that interventions aiming to adequate
      growth should focus on prenatal care and social and environmental factors during
      childhood as a way of ensuring full expression of the genetic potential of this
      population.

PMID- 17173166
TI  - Bat rabies in the north-northwestern regions of the state of Sao Paulo, Brazil:
      1997-2002.
AB  - OBJECTIVE: Reports on bat rabies in Brazil are sporadic and isolated. This study
      aimed at describing the detection of rabies virus in bats in the state of Sao
      Paulo. METHODS: A total of 7,393 bats from 235 municipalities of the north and
      northwestern areas of the state of Sao Paulo, Southeastern Brazil, were assessed
      according to their morphological and morphometric characteristics from 1997 to
      2002. Fluorescent antibody test and mice inoculation were used for viral
      identification. RESULTS: Of all samples examined, 1.3% was rabies virus positive,
      ranging from 0.2% in 1997 to 1.6% in 2001. There were found 98 bats infected, 87
      in the urban area. Fluorescent antibody test was detected in 77 positive samples,
      whereas 92 produced rabies signs in mice; incubation period ranging from 4 to 23
      days. In 43 cities at least one rabid bat was observed. The highest proportion
      (33.7%) of rabies virus was found in Artibeus lituratus. Eptesicus and Myotis
      were the most frequent positive species (24.5%) of the Vespertilionidae family.
      The species Molossus molossus and Molossus rufus showed 14.3% positive bats.
      There were no differences in the distribution of positive rabies between females
      (33; 48.5%) and males (35; 51.5%). CONCLUSIONS: Rabies-infected bats were found
      in environments that pose a risk to both human and domestic animal population and
      there is a need for actions aiming at the control of these species and public
      education.

PMID- 17173167
TI  - [Host feeding preferences of sandflies in rural area, Southern Brazil].
AB  - OBJECTIVE: To investigate the fauna and host feeding preferences of sandflies as
      for domestic animals in an endemic area of American cutaneous leishmaniasis.
      METHODS: The sandflies collections were carried out from 8:00 pm to 12:00 am in
      an area 40 meters away from one of the residences in a farm in Southern Brazil,
      between January and April, 2004. Collection was performed using four Falcao light
      traps, placed 5 m apart from each other beside a cage, each one of them
      containing an animal bait (swine, dog, rabbit, and chicken). RESULTS: A total of
      1,697 specimens of sandflies were collected as follows: Nyssomyia whitmani,
      Pintomyia fischeri, Migonemyia migonei, Nyssomyia neivai, Pintomyia pessoai and
      Psathromyia shannoni. The prevalent species was N. whitmani. There were no
      feeding preferences of sandflies as for the animals studied. CONCLUSIONS: N.
      whitmani and P. fischeri are opportunistic species and female insects probably
      adjust their eating habits to host availability, suggesting eating eclecticism of
      these insects in anthropic environments.

PMID- 17173168
TI  - [Spatial distribution of Aedes albopictus in the southern area of Mato Grosso do
      Sul State, Brazil].
AB  - OBJECTIVE: To investigate the spatial distribution of Aedes albopictus population
      to provide input for developing sampling plans and supporting decision making on
      the control of this vector in field sampling. METHODS: A study was carried out in
      an urban area that has a vestige of primary vegetation, 20 km away from Dourados,
      Midwestern Brazil. Ten samplings were conducted between January 28, 2003 and
      April 9, 2003, using ovitraps which were monitored once a week, and distributed
      in a fixed sample area with 10 collection points for each sampling 300 m away
      from each other. Aggregation indexes were calculated and adjusted to the
      following theoretical frequency distribution: negative binomial, positive
      binomial and Poisson's. RESULTS: The sample variance was higher than the sampling
      mean, resulting in mean-variance indexes above the unit (32.066, 29.410, 14.444,
      58.840, 56.042, 111.262, 70.140, 50.701, 93.221 and 8.481). Morisita's index was
      also statistically above the unit in all samplings (6.275, 3.947, 1.484, 3.725,
      3.014, 5.450, 3.214, 3.886, 3.954 and 5.810), and K parameter ranged 0 and 8
      (0.174, 0.309, 1.867, 0.332, 0.449, 0.203, 0.408, 0.314, 0.306 and 0.200). The
      Chi-square test for adjustment to the negative binomial distribution, positive
      binomial distribution, and Poisson's distribution was not statistically
      significant. CONCLUSIONS: Ae. albopictus population in the studied municipality
      showed an aggregated standard spatial distribution. This means that when
      individual vectors are found in a certain site, it is likely that other vectors
      can be found in the proximities, recommending insecticide spraying for vector
      control in this site without requiring sampling other sites in this same
      locality.

PMID- 17173169
TI  - [Seasonal variation of Aedes aegypti and Aedes albopictus in a city of
      Southeastern Brazil].
AB  - OBJECTIVE: To assess the seasonal variation of Aedes aegypti and Aedes albopictus
      and to estimate the association between the species abundance and abiotic
      factors. METHODS: Tire-traps were kept for a period of 15 days monthly in an
      urban area of the city of Potim in the state of Sao Paulo, Southeastern Brazil,
      from November 2002 to October 2003. Samples of immature forms were followed up
      under laboratory conditions for 29 days and species were identified. The
      association between abundance and temperature, rainfall and air relative humidity
      was tested using Spearman correlations (r s). The descriptive statistics were
      presented by the average and the standard error (alpha=0.05). RESULTS: From a
      total of 20,727 immatures collected, 95.3% were Ae. aegypti and 4.7%, Ae.
      albopictus. Ae. aegypti was found throughout the whole year while Ae. albopictus
      was found from November to July. The association between these species and
      abiotic factors was significant for Ae. aegypti (p=0.04) as for maximum
      temperature and for Ae. albopictus as for maximum temperature (p=0.01) and
      rainfall (p=0.02). CONCLUSIONS: Both species presented seasonal variation.
      However, Ae. aegypti was found throughout the whole year showing a decrease
      between April and May and June and July. Ae. albopictus, less abundant, was found
      only between November, 2002 and July, 2003 with a peak in April, 2003. The higher
      abundance of Ae. aegypti compared to Ae. albopictus in an urban area showed Ae.
      aegypti has greater capacity of colonizing tires. Such a breeding site in the
      environment may be important to the maintenance and abundance of Ae. aegypti.

PMID- 17173170
TI  - [Diversity of oviposition containers and buildings where Aedes albopictus and
      Aedes aegypti can be found].
AB  - OBJECTIVE: To assess the diversity of oviposition containers and buildings where
      females of Aedes albopictus and Aedes aegypti can be found. METHODS: A study was
      carried out in the city of Rio de Janeiro, Southern Brazil, between 2002 and
      2003. Larvae in different types of buildings were investigated, and immature
      forms found were then sent to the laboratory for identification. The larval
      frequency for both mosquitoes was estimated in the oviposition containers
      available. The Breteau index and the building infestation index were calculated
      and differences were tested using the Chi-square test. RESULTS: The types of
      buildings that were positive for Aedes albopictus and Aedes aegypti were:
      dwellings (83.9%); churches, schools, clubs (6.8%); vacant land (6.4%); and
      businesses (2.8%). Of 9,153 larvae collected, 12.0% were Aedes albopictus and
      88.0% were Aedes aegypti. Aedes albopictus were mostly found in drains (25.4%);
      cans, bottles, empty bottles (23.9%); and plant vases (16.2%). Aedes aegypti was
      much more frequently found than Aedes albopictus (chi(2)=145.067; p<0.001). Both
      species were significantly more frequent in artificial than in natural
      oviposition containers (chi(2)=31.46; p<0.001). The building infestation index
      and Breteau index for Aedes albopictus were 0.3% and 0.28% in 2002 and 0.4% and
      0.5 in 2003, respectively. For Aedes aegypti, they were 1.0%, 1.16 in 2002 and
      3.5% and 4.35 in 2003, respectively. CONCLUSIONS: The present study assessed the
      frequencies of Aedes albopictus and Aedes aegypti females in various types of
      oviposition containers and types of buildings. The abundant availability of
      artificial containers in dwellings, associated with the capacity of Ae.
      albopictus to be also found in natural oviposition containers, has greatly
      contributed for their gradual adaptation to human environment.

PMID- 17173171
TI  - Caffeine effect on mortality and oviposition in successive generations of Aedes
      aegypti.
AB  - OBJECTIVE: Previous experiments showed that caffeine blocks the development of
      Aedes aegypti (Diptera, Culicidae) in the larval stage, consequently inhibiting
      the production of adults. This study aimed at obtaining data suggestive of
      caffeine resistance by these mosquitoes. METHODS: Experiments were carried out in
      successive generations to assess adult production from eggs laid in previous
      generation and oviposition rate in every generation using 200 and 500 microg/mL
      caffeine. Tap water was used as control. Experiments were conducted in the city
      of Sao Jose do Rio Preto, Southeastern Brazil between 2002 and 2005. Statistical
      tests consisted of exploratory data analysis and smoothing algorithms. RESULTS:
      Increasing reduction in productivity of adults occurred among generations at both
      caffeine concentrations but the differences were only significant at 200microg/mL
      caffeine. As for the oviposition rate, there was a decrease in the mean number of
      eggs per female over generations at both caffeine concentrations. CONCLUSIONS:
      There was no evidence of caffeine resistance over generations. The study results
      corroborate caffeine as an alternative as an important Ae. Aegypti control agent
      to avoid resistance.

PMID- 17173173
TI  - [Long-term care elderly residents in general hospitals].
AB  - Long-term care facilities for the elderly have regularly to work together with
      general hospitals to provide care to acutely ill residents or when they require
      all together more complex diagnostic procedures and multi-specialty care. The
      decision to hospitalize a nursing home elderly resident is multifactorial and it
      is based on factors such as illness severity and care facility infrastructure.
      Hospitalizations have benefits and risks such developing iatrogenic diseases,
      delirium, and functional decline, which may deteriorate patients' general
      condition and their quality of life during and/or after hospitalization. This
      study aimed at addressing specific aspects of assessment, treatment and
      management of nursing home elderly who require to be hospitalized, especially
      focusing on their effective care. Common conditions such delirium, iatrogenic
      diseases, poor nutrition, functional decline, hospice care and special
      characteristics of nursing home elderly during their admission to general
      hospitals are discussed.

PMID- 17173172
TI  - [Anopheles cruzii parity in dense rain forest in Southern Brazil].
AB  - OBJECTIVE: To determine the parity and ovarian development of Anopheles cruzii
      species during the seasons. METHODS: Collections were carried out fortnightly in
      the morning in the Palmito State Park in the municipality of Paranagua, Southern
      Brazil, between April 2004 and April 2005. Adult mosquitoes were captured using
      human landing rate. Dissections were performed using Detinova's and Polovodova's
      methods and follicular development was assessed following Christophers and Mer's
      criteria. RESULTS: A total of 208 specimens of Anopheles cruzii were dissected.
      Most females dissected were nulliparous in the seasons; 14.4% of them were found
      to be nulliparous above Christophers and Mer's stage II, which shows previous
      blood meal prior to the first oviposition. It was observed that Anopheles cruzii
      populations comprised young mosquitoes, probably due to high mortality among
      parous females. CONCLUSIONS: The likely gonotrophic discordance is
      epidemiologically relevant because female mosquitoes can search for more than one
      host to complete the maturation of their eggs.

PMID- 17173174
TI  - [Program for promoting research in local health systems and services: shared
      health management].

PMID- 17173175
TI  - [Hepatitis B vaccine].

PMID- 17173177
TI  - Electron microscopic radioautographic study on protein synthesis in hepatocyte
      mitochondria of aging mice.
AB  - For the purpose of studying the aging changes of intramitochondrial protein
      synthesis in mouse hepatocytes, 10 groups of aging mice, each consisting of 3
      individuals (total 30), from fetal day 19 to postnatal month 24, were injected
      during development with 3H-leucine, a protein precursor, sacrificed 1 h later,
      and the liver tissues processed for electron microscopic (EM) radioautography. On
      EM radioautograms obtained from each animal, the number of mitochondria, the
      number of labeled mitochondria, and the mitochondrial labeling index labeled with
      silver grains due to 3H-leucine showing protein synthesis in each mononucleate
      hepatocytes were counted and the averages in respective aging groups were
      compared. From the results, it was demonstrated that the numbers of mitochondria,
      the numbers of labeled mitochondria, and the labeling indices of
      intramitochondrial protein syntheses in mononucleate hepatocytes of mice at
      various ages from embryonic day 19 to postnatal month 24 increased and decreased
      due to development and aging of animals.

PMID- 17173178
TI  - Ultrasonographic evaluation of parathyroid hyperplasia in dialysis patients.
AB  - Secondary hyperparathyroidism (SHPT) is one of the most common complications in
      patients with chronic kidney disease (CKD). Bone and mineral disorders, increased
      morbidity and mortality are the consequences of SHPT. Therefore, prevention and
      control of hyperparathyroidism is one of the main objectives in the management of
      patients with CKD, particularly in dialysis patients. It is well known that SHPT
      in CKD is not only a state of increased parathyroid hormone (PTH) synthesis and
      secretion, but more importantly, it is a state of parathyroid gland (PTG)
      hyperplasia. The serum concentration of intact PTH is the main method used to
      assess PTG overactivity. Unfortunately, estimating the size and shape of the PTG
      in SHPT diagnosis, i.e., parathyroid hyperplasia, is still neglected. Among the
      various procedures, ultrasonography could be the method of choice to detect PTG
      size and shape because of its simplicity and noninvasiveness. This method can be
      sufficiently sensitive to distinguish diffuse and nodular hyperplasia.

PMID- 17173179
TI  - Integrated confocal and scanning probe microscopy for biomedical research.
AB  - Atomic force microscopy (AFM) continues to be developed, not only in design, but
      also in application. The new focus of using AFM is changing from pure material to
      biomedical studies. More frequently, it is being used in combination with other
      optical imaging methods, such as confocal laser scanning microscopy (CLSM) and
      fluorescent imaging, to provide a more comprehensive understanding of biological
      systems. To date, AFM has been used increasingly as a precise micromanipulator,
      probing and altering the mechanobiological characteristics of living cells and
      tissues, in order to examine specific, receptor-ligand interactions, material
      properties, and cell behavior. In this review, we discuss the development of this
      new hybrid AFM, current research, and potential applications in diagnosis and the
      detection of disease.

PMID- 17173180
TI  - Osteoporosis in Rett syndrome: A study on normal values.
AB  - Osteoporosis is the reduction of calcium density in bones, usually evident in
      postmenopausal females, yet the tendency for osteoporosis can also be identified
      at a young age, especially in patients with chronic diseases, disabilities, and
      on chronic anticonvalsant treatment. Individuals with Rett syndrome (RS) have
      been found to show signs of osteoporosis at a young age. This condition may cause
      pathological fractures, inflict pain, and seriously damage mobility. In such
      cases, the quality of life of the individual and her primary caretakers will be
      severely hampered. This article reviews the current knowledge of the phenomenon
      and suggests some clinical directions for the individual with RS who shows signs
      of osteoporosis. The article also presents novel findings from a screening test
      of bone strength in 35 individuals with RS at different ages using the Sunlight
      Omnisense 7000P ultrasound apparatus. The primary results from this investigation
      showed a strong and significant positive correlation between calcium intake and
      bone strength (p < 0.0001) as well as bone density Z values (p < 0.005). The
      occurrence and frequency of fractures were found connected with reduced bone
      strength in measurements of both the radius (p < 0.0001) and the tibia (p <
      0.004) as well as with negative bone strength Z values (p = 0.03). Other findings
      specified within the content of the article support the implementation of a
      comprehensive antiosteoporotic preventive management for this population.

PMID- 17173181
TI  - Health effects of long-term exposure to insecticide-treated mosquito nets in the
      control of malaria in endemic regions, revised.
AB  - The endemicity of malaria in tropical areas of the world persists, especially in
      countries south of Saharan Africa. The efforts and concerns invested by the World
      Health Organization and other health agencies to eradicate malaria are
      commendable. However, in spite of all these efforts, the loss in economic and
      human resources continues. In a previous report, the long-term health effects of
      insecticide-impregnated bednet (IIBN) use were highlighted with the expectation
      of attracting serious thoughts and further research on the issue. This present
      paper is an update on that expectation. Results from a comprehensive literature
      search show that not much work has been done on the effects of long-term exposure
      to IIBNs in combating malarial infection. The efficacy of IIBNs is not in
      question. What is in question is whether long-term exposure to IIBNs have any
      health effects. The aims and outcomes of the research found in the literature on
      the subject to date seem to support only the efficacy of the temporal use of
      plain bednets, but not the use of IIBNs, and do not tell much about the long-term
      effects of IIBN exposure. All pesticides are toxic by nature and present risks of
      adverse effects. While there is agreement that IIBNs can be effective in reducing
      malarial morbidity and mortality under field trials, a number of factors relating
      to their long-term-exposure health effects have yet to be determined. Further
      reliable research projects are recommended urgently. However, some of the
      anticipated behavioral effects caused by insecticidal use will be avoided by the
      use of untreated nets instead.

PMID- 17173183
TI  - Human development x: Explanation of macroevolution--top-down evolution
      materializes consciousness. The origin of metamorphosis.
AB  - In this paper, we first give a short discussion of the macroevolution viewing
      life as information-directed, complex, dynamic systems. On this basis, we give
      our explanation of the origin of life and discuss the top-down evolution of
      molecules, proteins, and macroevolution. We discuss these subjects according to
      our new holistic biological paradigm. In view of this, we discuss the
      macroevolution of the organism, the species, the biosphere, and human society.
      After this, we discuss the shift in evolution from natural selection to a new
      proposed process of nature called the "metamorphous top-down" evolution. We
      discuss the capability of the evolutionary shift to govern some of the processes
      that lead to the formation of new species. We discuss the mechanisms we think are
      behind this proposed shift in evolution and conclude that this event is able to
      explain the huge biological diversity of nature in combination with evolutionary
      natural selection. We also discuss this event of nature as an isolated, but
      integrated, part of the universe. We propose the most important genetic and
      biochemical process that we think is behind the evolutionary shift as a
      complicated symbiosis of mechanisms leading to metamorphosis in all biological
      individuals, from bacteria to humans. The energetic superorbital that manifests
      the consciousness governs all these processes through quantum chemical activity.
      This is the key to evolutionary shift through the consciousness, and we propose
      to call this process "adult human metamorphosis".

PMID- 17173182
TI  - Amylin in the periphery II: An updated mini-review.
AB  - Amylin is a polypeptide that is cosecreted with insulin from the beta cells of
      the pancreas. Therefore, in states of diabetes in which the beta-cell mass is
      largely depleted or dysfunctional, insulin and amylin secretion are also lost or
      dysregulated. While the soluble monomeric form of amylin acts as a hormone that
      alters physiological responses related to feeding and acts as a specific growth
      factor, there has been renewed interest in the less-soluble oligomeric and
      insoluble polymeric forms of human (also monkey and cat) amylin that may
      contribute to the establishment of a pathophysiological pathway to overt
      diabetes. With this discovery has grown the hope of minimizing, with appropriate
      therapy, these toxic forms to preserve the functional (c) not-cell mass. Human
      beta cells may also be more vulnerable to these forms and one risk factor, a
      higher fat diet, may promote toxic forms. The generation and utilities of
      transgenic rodent models, which express enhanced levels of human amylin, have
      been accompanied by strategies that may lead to the reduction of toxic forms and
      associated risk factors. The successful definition and faithful expression of the
      physiological receptors (and complexes) for amylin that may differ for each
      target organ is an important development in the field of amylin research
      generally. Besides the heuristic value for the understanding of the molecular
      biology of receptors, the opportunity to screen and identify nonpeptide analogues
      that bind the physiological receptors has important implications for biomedicine
      and clinical practice in relation to treatments for diabetic complications, bone
      diseases, and eating disorders. In particular, in their capacities to mimic the
      effects of amylin as a growth factor, amylin analogues may prove useful in the
      stimulation of beta-cell mass (in conjunction with other factors), reduce the
      activity of the osteoclast population, and stimulate the regeneration of proximal
      tubules following toxic insult (and thus avoid the development of renal
      insufficiency).

PMID- 17173184
TI  - Phospholipid scramblase 1.
AB  - Phospholipid scramblase 1 (PLSCR1) is a calcium-binding, multiply palmitoylated
      type II endofacial plasma membrane protein, while unpalmitoylated PLSCR1 protein
      can import into the nucleus, where it binds to genomic DNA. Although the original
      work showed that PLSCR1 contributes to the transbilayer movement of
      phospholipids, the following studies revealed that PLSCR1 expression can be
      induced by some cytokines such as interferon, epidermal growth factor, and also
      by leukemic cell differentiation-inducing agents such as all-trans retinoic acid
      (ATRA) and phorbol 12-myristate 13-acetate (PMA). PLSCR1 was also shown to
      interact with several protein kinases including c-Abl, c-Src, protein kinase
      Cdelta as well as some other proteins such as onzin, suggesting the roles of
      PLSCR1 in cell signaling. Indeed, the current evidence proposes that PLSCR1
      contributes to cell proliferation, differentiation, apoptosis, and plays roles in
      the pathogenesis of cancers, especially leukemia.

PMID- 17173185
TI  - Forebrain NMDA receptors contribute to neuronal spike responses in adult mice.
AB  - Glutamate is the major fast excitatory transmitter in the central nervous system.
      While normal synaptic transmission is mediated by alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA) and kainate receptors, N-methyl-D-aspartate
      (NMDA) receptors are thought to selectively contribute to plasticity. Genetically
      enhancing NMDA receptor functions enhances animal behavior in normal
      physiological learning and enhances their sensitivity in the case of tissue
      injury. One major mechanism for NMDA receptors is synaptic long-term potentiation
      (LTP). Here we present evidence that NMDA receptors not only contribute to normal
      synaptic responses induced by stimulation of local layer V or white matters, but
      also contribute to generation of action potentials induced by a depolarizing step
      applied to the soma. Calcium-calmodulin sensitive adenylyl cyclase 1 and cAMP
      signal pathways likely mediate these effects. Considering the importance of
      cingulate neurons in nociception and pain, our results provide a new mechanism
      for NMDA receptor contributing to neuronal synaptic transmission, spiking
      properties in forebrains, and possible forebrain-related behavioral nociceptive
      responses and pain.

PMID- 17173186
TI  - Generation and characterization of antibody against paf1 complex in Drosophila
      melanogaster.
AB  - Paf1 complex was identified in yeast and characterized to function in
      transcription and its related events. We identified the Drosophila homological
      components of paf1, CDC73 and RTF1 of paf1 complex. The genes encoding Drosophila
      paf1, CDC73 and RTF1 were cloned and expressed. With the purified recombinant
      proteins of truncated components of paf1 complex, antibodies against the
      Drosophila paf1, CDC73 and RTF1 were generated. These antibodies have been shown
      to be able to detect the endogenous paf1 subunits as well as their human
      counterparts in the HeLa extract. On Drosophila polytene chromosomes, these
      antibodies have been demonstrated to locate the paf1 complex at actively
      transcribing sites, which co-localized with phosphorylated RNA polymerase II,
      indicating that paf1 complex in Drosophila is involved in transcription or the
      events coupling with transcription.

PMID- 17173188
TI  - [Calreticulin expression increases during delayed cardioprotection induced by
      hypoxic preconditioning].
AB  - Both in vivo and cultured cardiomyocyte experiments were performed to investigate
      the alteration of expression of calreticulin (CRT) during the delayed
      cardioprotection induced by hypoxic preconditioning (HPC) and the intracellular
      signal transduction mechanisms of the alteration. (1) Wistar rats were randomly
      divided into three groups: sham operation group (Sham), myocardial infarction
      (MI) group induced by left coronary artery ligation and HPC+MI group (4-hour HPC
      24 h before MI). Twenty-four hours, 14 d and 28 d after left coronary artery
      ligation, myocardial function, infarction size and the area at risk were
      measured. Western blot was used to detect the expression of CRT, the activity of
      p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase
      (SAPK). (2) Cultured cardiomyocytes from neonatal Sprague-Dawley (SD) rat were
      divided into six groups: hypoxia/reoxygenation (H/R), HPC, HPC+H/R, p38 MAPK
      inhibitor SB203580+HPC+H/R (SB+HPC+H/R), SAPK inhibitor SP600125+HPC+H/R
      (SP+HPC+H/R) and control. Survival rate and apoptosis rate of cardiomyocytes 6 h
      after H/R and activities of lactate dehydrogenase (LDH) in culture medium in each
      group were measured. Western blot was used to detect the expression of CRT and
      activities of p38 MAPK and SAPK. The results are as follows: (1) During in vivo
      experiment, compared with MI group, HPC significantly improved +dp/dt(max) and 
      dp/dt(max), reduced infarction size and the area at risk. HPC dramatically
      changed the expression of CRT. CRT expression in HPC+MI group was 206% of that in
      MI group (P<0.05) 24 h after infarction, especially in the area at risk. However,
      28 d after operation, the expression of CRT decreased by 57%. Correlation
      analysis indicated a positive correlation between CRT expression and myocardial
      function (r=0.9867, P<0.05), and negative correlation between CRT expression and
      infarction size (r=-0.9709, P<0.05). (2) In cultured cardiomyocytes, HPC
      attenuated cell injury induced by H/R. CRT expression increased moderately to
      222% of control (P<0.05) during HPC, but increased dramatically to 503% of
      control (P<0.05) after H/R. HPC reduced H/R-induced CRT up-regulation to 56% of
      that in H/R group (P<0.05). Correlation analysis indicated that CRT expression
      induced by HPC had a positive correlation with p38 MAPK activity (r=0.9021,
      P<0.05), but a negative correlation with SAPK activity (r=-0.8211, P<0.05). Both
      in vivo and in vitro results indicate that HPC protects myocardium from ischemia
      or H/R injury. p38 MAPK is possibly involved in the up-regulation of CRT induced
      by HPC, while SAPK has a negative influence.

PMID- 17173187
TI  - [Differential reversal effect of intrathecal bovine adrenal medulla peptide 22 on
      morphine tolerance in rats].
AB  - Bovine adrenal medulla 22 (BAM22), an endogenous opioid peptide, is one of the
      cleavage products of proenkephalin A. It potently activates opioid receptors and
      sensory neuron-specific receptor (SNSR). The present study was aimed at
      investigating the effect of BAM22 on morphine tolerance. Intrathecal (i.t.)
      administration of morphine for 7 d produced morphine tolerance in rats. Then the
      rats were divided into three groups in which morphine, saline or BAM22 were
      administered i.t., respectively, on day 8, and morphine was given to all of the
      animals on day 9. It was found that morphine administered on day 9 resumed
      antinociceptive effects in BAM22 group, but not in saline or morphine group. The
      potency of morphine in BAM22 group was 48.5% of the maximal possible effect (MPE)
      detected by paw withdrawal test and the antinociception persisted for
      approximately 1 h. Following the similar treatment, morphine administered on day
      9 reduced nocifensive behaviors by 3.2 min and 24 min in BAM22 group in the first
      and second phases, in the formalin test, respectively. The decreases were 45% and
      82% of the corresponding values observed in saline group. Furthermore, following
      the treatment with BAM22 (10 nmol) on day 8 in morphine-tolerance rats, morphine
      administered on day 9 decreased the expressions of the heat-evoked c-Fos-like
      immunoreactivity (FLI) protein by approximately 80% in laminae I-II, III-IV and V
      VI in the spinal cord at L4-L5 compared with that in saline or morphine group.
      The present study provided evidence at behavioral and cellular levels showing
      that BAM22 resumed antinociception of morphine. The results that the reversal
      effect of BAM22 on morphine tolerance was more efficient in persistent pain model
      than in acute pain may indicate that BAM22 differentially modulates morphine
      tolerance. The present study suggests that SNSR is involved in the modulation of
      morphine tolerance.

PMID- 17173189
TI  - Promotive action of lysophosphatidic acid on proliferation of rat embryonic
      neural stem cells and their differentiation to cholinergic neurons in vitro.
AB  - Effects of lysophosphatidic acid (LPA), an extracellular phospholipid signal, on
      the proliferation of rat embryonic neural stem cells (NSCs) and their
      differentiation into microtubule-associated protein 2 (MAP2)-positive and choline
      acetyltransferase (ChAT)-positive, i.e. cholinergic-committed neurons, were
      observed in vitro by [(3)H]-thymidine incorporation, immunocytochemistry, Western
      blot and other techniques. The results showed that: (1) Lower concentrations of
      LPA (0.01~1.0 mumol/L) dose-dependently enhanced the uptake of [(3)H]-thymidine
      by NSCs cultured in specific serum-free medium, indicating a significant
      promotive action of LPA on the proliferation of NSCs. (2) After fetal bovine
      serum which induces and commences the differentiation of NSCs, was used in the
      medium, the lower concentrations of LPA increased the percentages of both MAP2-
      and ChAT-immunoreactive neurons, with a peak at 0.1 mumol/L LPA in two cases. (3)
      The promotive effects of LPA on the differentiation of MAP2- and ChAT-positive
      neurons were also supported by the up-regulation of the expressions of both MAP2
      and ChAT proteins detected by Western blot. (4) At the early phase of
      differentiation of NSCs, the cell migration and neurite extension were enhanced
      significantly by lower dosages of LPA under phase-contrast microscope. These
      results suggest that LPA within certain lower range of concentrations promotes
      the proliferation of NSCs and their differentiation into unspecific MAP2-positive
      and specific cholinergic-committed neurons, and also strengthens the migration
      and neurite extension of the newly-generated neuronal (and also glial as reported
      elsewhere) progenitors.

PMID- 17173190
TI  - [Alteration of signal transduction-associated gene expression in rat cardiac
      fibroblasts induced by blocking angiotensin II receptors].
AB  - To investigate the molecular mechanism of angiotensin II (Ang II) receptor
      activation in adult rat cardiac fibroblasts, the expressions of cell signal
      transduction-associated genes were studied by using cDNA microarray. Cardiac
      fibroblasts of adult Sprague-Dawley rats (230~250 g) were isolated and cultured.
      The cells were divided into 4 groups: Ang II, Ang II + losartan, Ang II +
      PD123319, Ang II + losartan + PD123319. The expressions of Ang II receptors were
      studied by immunohistochemical staining. Total RNA was extracted and purified.
      After cDNA synthesis and biotin-16-dUTP labeling, the probes were denatured and
      hybridized with GEArray Q Series mouse G Protein-coupled Receptors Signaling
      Pathway Finder Gene Array (MM-025) containing 96 genes associated with 11
      pathways. The arrays were scanned with a Uniscand1000 scanner and further
      analyzed with GEArray Analyzer software. RT-PCR was used to further confirm the
      results of gene microarray. The results of immunohistochemical staining showed
      that the expression of Ang II type 2 (AT2) receptor was evidently induced by Ang
      II stimulation when Ang II type 1 (AT1) receptor was blocked. The results of gene
      array indicated that blocking AT1 receptor changed 34 genes (more than 2 folds),
      30 were down-regulated and 4 were up-regulated. The maximum change was not beyond
      20 folds. The following 9 pathways were activated: cAMP/PKA, Ca2+, PKC, PLC,
      MAPK, PI-3 kinase, NO-cGMP, Rho, NF-kappaB pathways. Blockade of AT2 receptor
      caused 64 genes changing more than 2 folds (48 were down-regulated and 16 were up
      regulated). Eleven pathways were basically activated. The change of the following
      7 genes was over 30 folds: Cyp19a1 (37 folds), Il1r2 (42 folds), Cflar (53
      folds), Bcl21 (31 folds), Pik3cg (278 folds), Cdkn1a (90 folds), Agt (162 folds).
      According to the activated extent, the signal transduction pathways in turn were
      PI-3 kinase, NF-kappaB and JAK-STAT pathways. Blocking both AT1 and AT2 receptors
      changed 46 genes more than 2 folds (36 were down-regulated and 10 were up
      regulated). Eleven pathways were basically activated. The results of RT-PCR of IL
      1beta and TNF-alpha confirmed the observations in gene microarray. Our results
      show that Ang II can induce a high expression of AT2 receptor in adult rat
      cardiac fibroblasts when AT1 receptor is blocked, and the signal mechanism of AT2
      receptor is clearly different from that of AT1 receptor.

PMID- 17173191
TI  - Expression of calbindin-D28k in human fallopian tubes.
AB  - The present study was aimed at investigating the expression of calbindin-D28k
      (CaBP-D28k) in human fallopian tube, which were collected from 33 childbearing
      age women undergoing abdominal hysterectomy with adnexectomy for benign disease
      in the pelvic cavity. These women had normal menstrual cycle and history of
      normal pregnancy. Isthmus, ampullary and umbrella segments of fallopian tubes
      were respectively collected. These specimens were divided into 6 groups based on
      their menstrual cycles: early-proliferative stage (n=6), mid-proliferative stage
      (n=5), late-proliferative stage (n=5), early-secretory stage (n=7), mid-secretory
      stage (n=5) and late-secretory stage (n=5). The expressions of CaBP-D28k protein
      and mRNA in fallopian tubes were determined by immunohistochemistry and reverse
      transcription polymerase chain reaction (RT-PCR) methods. Positive expressions of
      CaBP-D28k protein and mRNA were observed in human fallopian tubes. There was no
      significant difference in the expression of CaBP-D28k protein among the isthmus,
      ampulla and umbrella segments in the same phase of menstrual cycle (P>0.05).
      However, in the menstrual cycle, the expression level of CaBP-D28k protein in the
      epithelium was the lowest during the early- and mid-proliferative stages and
      increased in both the late-proliferative and early-secretory stages (P<0.05), and
      then decreased in the mid- and late-secretory stages (P<0.05). The expressed CaBP
      D28k protein was disposed to gobbets or dispersed sheets in cytoplasm in the
      early- and mid- proliferative stages, and showed concentrated granules on the top
      of cells in the late-proliferative and early-, mid-secretory stages. Then in the
      late-secretory stage redistribution renewed as in the early- and mid
      proliferative stages. The CaBP-D28k mRNA obviously increased in the late
      proliferative and early-secretory stages (P<0.05). These findings indicate that
      the expressions of CaBP-D28k protein and mRNA exist in human fallopian tubes and
      exhibit a cyclic change.

PMID- 17173192
TI  - [Exogenous estrogen improved calcium homeostasis and skeletal mineralization in
      vitamin D receptor gene knockout female mice].
AB  - It is well known that estrogen can inhibit bone absorption, decrease bone
      turnover and preserve bone mass. Some studies indicated that the effect of
      estrogen on calcium and bone is relative to vitamin D system, while others also
      reported that this effect of estrogen is independent of vitamin D. The genomic
      effect of 1alpha, 25(OH)(2)D(3)is mediated by the nuclear vitamin D receptor
      (VDR) in a ligand-dependent manner. Hypocalcemia, hyperparathyroidism and
      osteomalacia are developed in VDR gene knockout mice. To determine whether the
      effect of estrogen on calcium and bone is dependent on VDR, this study examined
      the effect of exogenous estrogen on calcium and bone homeostasis in VDR gene
      knockout mice. Male and female wild type (WT) and VDR gene knockout heterozygous
      mice were mated each other and the genotyping of their offsprings were determined
      by PCR. At age of 21-day, WT and knockout mice were weaned and treated by one of
      three different regimens: (1) WT-vehicle group: the WT mice were injected with
      normal saline; (2) VDR KO-vehicle group: the VDR gene knockout mice were injected
      with normal saline; (3) VDR KO-E group: the VDR gene knockout mice were
      subcutaneously injected with estradiol, 0.2 mug per mouse, once daily for 1
      month. The bone mineral density (BMD) of mice was measured using dual-energy X
      ray absorptiometry. All mice were sacrificed at age of 50-day. Blood was taken by
      heart puncture under anesthesia and serum calcium was measured by
      autoanalyser.Tibiae were removed, fixed and embedded with the methylmethacrylate
      (MMA), and undecalcified sections were cut. These sections were stained for
      mineral with the von Kossa staining procedure and counterstained with toluidine
      blue. Static histomorphometric analyses were performed on those stained sections.
      The results showed that the serum calcium level was (2.10+/-0.37) mmol/L in the
      VDR KO-vehicle mice and rose to (2.80+/-0.41) mmol/L in the VDR KO-E mice
      although it was still lower than WT-vehicle mice [(3.10+/-0.48) mmol/L]. BMD and
      mineralized trabeculer volume were increased significantly in VDR KO-E group
      compared with that in VDR KO-vehicle group. These results suggest that exogenous
      estrogen can improve calcium absorption and skeletal mineralization in a VDR
      independent manner.

PMID- 17173193
TI  - [Gender-dependent difference of NF-kappaB expression in the hippocampus of
      prenatally stressed offspring rats].
AB  - In this study, immunohistochemistry and Western blot were used to determine
      whether the expression of NF-kappaB in the hippocampus of prenatally stressed
      offspring rats is gender-dependent. The results were as follows: In the female
      offspring rats, the expressions of p65 in the hippocampal dentate gyrus in mid
      term stress (MS) and late-term stress (LS) groups were significantly less than
      that in the control group (P<0.01). There was a significant difference between MS
      and LS groups (P<0.01). The expressions of p50 in all regions of hippocampus in
      MS and LS groups were significantly more than that in the control group (P<0.01).
      A significant difference was also present between MS and LS groups (P<0.01). In
      the male offspring rats, the expressions of p65 in the hippocampal dentate gyrus
      in MS and LS groups were evidently more than that in the control group (P<0.01).
      There was a significant difference between MS and LS groups (P<0.01). The
      expressions of p50 in all regions of hippocampus in MS and LS groups were
      significantly less than that in the control group (P<0.05, P<0.01). There was
      also a significant difference in p65 expression between MS and LS groups
      (P<0.01). In addition, in the control group the expressions of p65 in the
      hippocampal dentate gyrus of female offspring rats were significantly more than
      that of male ones (P<0.01). However, in LS group the expressions of p65 in the
      hippocampal dentate gyrus of female offspring rats were significantly less than
      that of male ones (P<0.01). Moreover, there was no significant difference in p65
      expression between female and male offspring rats in MS group. In the control
      group the gender difference in the expression of p50 was only observed in
      hippocampal CA1 (P<0.01). The expressions of p50 in all regions of hippocampus of
      female offspring rats were significantly more than that of male ones in LS group
      (P<0.01). There was no significant difference in p50 expression between female
      and male offspring rats in MS group. The results of Western blot were similar to
      those of immunohistochemical study. These results indicate that prenatal stress
      in different gestational periods significantly affects the expressions of p65 and
      p50 in hippocampus, and this effect is gender-dependent. This may be one of the
      mechanisms underlying the gender difference in the ability of learning and memory
      of the prenatally stressed offspring rats.

PMID- 17173194
TI  - Puerarin decreases lens epithelium cell apoptosis induced partly by peroxynitrite
      in diabetic rats.
AB  - The present study was designed to observe if puerarin decreases lens epithelium
      cell (LEC) apoptosis induced partly by peroxynitrite (ONOO(-)). One hundred and
      eight rats were randomly divided into control group (n=36), streptozotocin (STZ)
      group (n=36) and STZ + puerarin group (n=36). The rats in the control group
      intraperitoneally (i.p.) received 0.5 ml of saline. The rats in STZ group and STZ
      + puerarin group received intraperitoneal injection of STZ (45 mg/kg). Three days
      later, the rats in STZ + puerarin group were given puerarin (140 mg/kg per day,
      i.p.). On days 20, 40 and 60 of the experiment, morphologic changes of lenses
      were observed with slit lamp. Then the animals were sacrificed for further
      analysis. The amount and percentage of apoptotic LECs were determined by flow
      cytometry. Nitrotyrosine (NT, the foot print of ONOO(-)) was examined by
      immunohistochemistry. Apoptosis-related genes (iNOS, etc.) were analyzed by gene
      array. The results showed that in the control group, all the lenses were clear.
      In STZ group, gradually severe opacity of the lens was observed on days 20, 40
      and 60. But in STZ + puerarin group, mild opacity of the lens was observed on day
      20 and more severe on day 40, but markedly decreased on day 60. In the control
      group, mild apoptosis of LECs was observed. In STZ group, time-dependent increase
      in apoptosis of LECs was observed. In STZ + puerarin group, mild apoptosis of
      LECs was observed on day 20, significantly increased on day 40, but markedly
      decreased on day 60. There was no expression of NT in the lens in the control
      group, but an increased expression of NT in STZ group. In STZ + puerarin group,
      mild expression of NT was observed on day 20, significantly increased on day 40,
      but markedly decreased on day 60. There was no expression of iNOS in the lens in
      the control group, but continuous up-regulation of iNOS expression in STZ group.
      In STZ + puerarin group, mild expression of iNOS was observed on day 20,
      significantly increased on day 40, but markedly decreased on day 60. Except the
      changes of iNOS related to NO production, the other apoptosis-related genes,
      including BCL-2 and SOD were down-regulated, while NF-kappaB and TNFR1-FADD
      caspase signal transduction way were up-regulated in STZ group. The results were
      opposite in STZ + puerarin group and the control group. These findings show that
      NT is expressed in diabetic rat lens, which proves that LEC apoptosis in diabetic
      lens is partly induced by ONOO(-) which may be a new oxidative damage way to form
      cataract. Puerarin partly decreases LEC apoptosis induced by ONOO(-) and is a
      potential medicine for therapy of diabetic cataract. The mechanism of puerarin
      dealing with diabetic cataract may be related to its direct inhibition of LEC
      apoptosis and antagonism of ONOO(-) in diabetic rats.

PMID- 17173195
TI  - [N(omega)-nitro-L-arginine methyl ester inhibits the up-regulated expression of
      neuronal nitric oxide synthase/NMDA receptor in the morphine analgesia tolerance
      rats].
AB  - The effect of systemic administration of nonspecific nitric oxide synthase
      inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia
      tolerance was observed by using the thermal tail-flick method, and the roles of
      NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis
      of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and
      midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into
      six groups (6 rats per group). Group 1, control group, received a subcutaneous
      (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment
      groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10
      mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10
      mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and
      17:00). The tail-flick latency (TFL) was measured in each rat before the
      injection as a baseline value, and then TFL at 50 min after the 1st injection
      every day as the measuring values. The animals (except for groups 2 and 5) were
      decapitated at 80 min after the last injection on the 8th day. The spinal
      segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A
      mRNA expressions by the RT-PCR method. The results showed that TFL remained
      unchangeable in group 2 compared with baseline value during the 7-day
      observation, while increased significantly on the 7th day in group 3. In group 4,
      TFL was longest on the 1st day, then decreased gradually from the 2nd day to the
      6th day, and restored to the baseline value on the 6th day. In group 5, TFL
      showed a decreasing tendency during the 7-day observation, but was still
      significantly longer than the baseline value on the 7th day. The changes of TFL
      obtained in group 6 were similar to those in group 5. The results of RT-PCR
      showed that as compared with group 1, nNOS mRNA expressions in spinal cord and
      midbrain were significantly down-regulated in group 3, but the expressions of the
      NR1A mRNA and NR2A mRNA in both groups were similar, while the nNOS mRNA, NR(1A)
      mRNA and NR(2A) mRNA expressions were all significantly up-regulated in group 4.
      As compared with group 4, the expressions of nNOS mRNA, NR(1A) mRNA and NR(2A)
      mRNA were significantly inhibited in group 6. These results suggest that the
      expressions of nNOS and NMDA receptors in spinal cord and midbrain were
      significantly up-regulated in the rats with morphine analgesia tolerance. Chronic
      co-administration of L-NAME could effectively inhibit the morphine-induced
      overexpressions of nNOS and NMDA receptors, and postpone the development of
      morphine analgesia tolerance. Based on the results of this study, it is concluded
      that NO/NMDA receptor in spinal cord and midbrain is closely related to the
      development of morphine analgesia tolerance.

PMID- 17173196
TI  - [Apoptosis of hypertrophic cardiomyocytes stimulated by hypoxia-reoxygenation is
      partially mediated by apoptosis-inducing factor].
AB  - Cardiomyocyte apoptosis leads to the functional incapacitation of myocardial
      plasmodium and plays an important role in the pathogenesis of heart failure
      transformed from compensable cardiac hypertrophy. Mitochondria are the main
      source of apoptosis-inducing molecule of various cells, and the role of
      caspartate-specific cysteinyl proteinase (caspase)-dependent mechanism has
      generally been accepted in the cardiomyocyte apoptosis. However, the significance
      of caspase-independent apoptosis-inducing factor (AIF) mechanism is not yet
      understood. The purpose of this study was to evaluate hypoxia-reperfusion-induced
      alterations of AIF mRNA and protein expressions in hypertrophic cardiomyocytes.
      Cardiomyocyte hypertrophy was produced by angiotensin II (0.1 mumol/L). The cells
      were cultured under the condition of hypoxia (95% N2 and 5% CO2; the O2 partial
      pressure was lower than 5 mmHg) for 8 h or 12 h (named as H8h and H12h groups,
      respectively), and then exposed to normal culture environment (named as H8h/R and
      H12h/R groups, respectively). Apoptosis was detected with Hoechst 33258 staining.
      The AIF mRNA and protein expressions were detected by RT-PCR and Western blot and
      quantified by gel scanning. The results were as follows: (1) The level of AIF
      mRNA expression was 0.29+/-0.08 (optical density, relative value) in the control
      group (hypertrophic cardiomyocytes cultured in normal environment). Compared with
      that in the control group, the levels of AIF mRNA expression were significantly
      higher in the groups of H8h and H12h (0.52+/-0.04 and 0.85+/-0.10), indicating
      that this effect was time-dependent. A further increase of AIF mRNA expression
      was observed in the groups of H8h/R (1.09+/-0.12) and H12h/R (1.41+/-0.23). (2)
      The level of AIF protein expression was 0.29+/-0.04 in the control group.
      Compared with that in the control group, the levels of AIF protein expression
      were significantly higher in the groups of H8h and H12h (2.07+/-0.15 and 3.12+/
      0.19). The AIF protein expression was increased further in the groups of H8h/R
      (4.57+/-0.25) and H12h/R (5.71+/-0.27). The nuclear translocation of AIF protein
      was obvious only in the groups of H8h/R and H12h/R. (3) The expressions of AIF
      mRNA and protein were almost completely inhibited by AIF siRNA transfection. The
      siRNA transfection also reduced the apoptosis of hypertrophic cardiomyocytes in
      the groups of H8h/R and H12h/R but not in the groups of H8h and H12h. The
      apoptosis rate was significantly reduced by both AIF siRNA transfection and Ac
      DEVD-cmk, an inhibitor of caspase-3. This reduction induced by two factors was
      more evident than that by one factor. (4) AIF nuclear translocation induced by
      hypoxia-reperfusion was not affected by inhibition of the activity of caspase-3.
      These data suggest that AIF plays a pivotal role in the apoptosis of hypertrophic
      cardiomyocytes induced by hypoxia-reperfusion.

PMID- 17173197
TI  - A ventricular pressure-clamping system for the study of mechano-electrical
      feedback.
AB  - It is necessary to control the mechanical stimuli precisely in the studies of
      cardiac mechano-electrical feedback (MEF). In the present study a ventricular
      pressure-clamping system has been developed, which can be applied to isolated
      perfused rabbit hearts. Controlled by a computer, this system not only can make
      the left ventricle follow a command defining the same pressure wave as that
      during a beating cycle under physiological condition, but also deliver mechanical
      stimuli with a proper waveform to the ventricle at a particular time phase. This
      system integrates multiple functions, including perfusing, pacing, recording of
      electrocardiogram and monophasic action potentials, and clamping and measuring of
      ventricular pressures in isolated-perfused hearts. Thus, it is a distinct system
      for investigating the phenomena and mechanisms of cardiac MEF at organ level.

PMID- 17173198
TI  - Work-related stress and health--risks, mechanisms and countermeasures.

PMID- 17173199
TI  - New systems of work organization and workers' health.
AB  - This paper aims at identifying major changes in and around work organizations,
      their effects upon job characteristics and the health and well-being of today's
      employees, and related research challenges. Increased internationalization and
      competition, increased utilization of information and communication technology,
      the changing workforce configuration, and flexibility and new organizational
      practices are considered. As work has changed from physical to mental in nature,
      job characteristics have changed significantly. Meanwhile work and family life
      have blended. New systems of work organization have become more prevalent, but
      they do not represent a radical change across the whole economy. New practices
      may have an adverse impact upon job characteristics, but their effects depend on
      their design, implementation, and management. Research recommendations include
      improved monitoring of changes in work organization and studies into their health
      and safety consequences, intervention studies, studies into the motivating
      potential of modern work practices, studies of marginalized workers and workers
      in less developed countries, and "mechanism studies".

PMID- 17173200
TI  - Work stress in the etiology of coronary heart disease--a meta-analysis.
AB  - OBJECTIVES: This study focused on estimating the relative risk of coronary heart
      disease (CHD) in association with work stress, as indicated by the job-strain
      model, the effort-reward imbalance model, and the organizational injustice model.
      METHODS: A systematic review and meta-analysis of prospective cohort studies were
      carried out. Studies were eligible if they had published a quantitative estimate
      of the association between work stress and incident CHD or cardiovascular
      mortality by January 2006. RESULTS: Fourteen prospective cohort studies were
      identified. For a total of 83 014 employees, the age- and gender-adjusted
      relative ratio of CHD for high versus low job strain was 1.43 [95% confidence
      interval (95% CI) 1.15-1.84], but the ratio decreased to 1.16 (95% CI 0.94-1.43)
      after adjustment for risk factors and potential mediators. The age- and gender
      adjusted risk ratio for a combination of high efforts and low rewards was 1.58
      (95% CI 0.84-2.97) for 11 528 employees, and no reduction in the risk ratio was
      seen after further adjustments. For organizational injustice, the age- and gender
      adjusted, and multiple-adjusted relative risks were 1.62 (95% CI 1.24-2.13) and
      1.47 (95% CI 1.12-1.95), respectively, for a population of 7246 men and women.
      There was little standardization in the assessment of work stress within all
      three stress models, and significant heterogeneity in the effects of stress was
      observed between studies. Few studies were available for female samples.
      CONCLUSIONS: Observational data suggest an average 50% excess risk for CHD among
      employees with work stress. Further research is needed to confirm that a
      reduction in work stress will lead to a reduction in CHD risk.

PMID- 17173201
TI  - Psychosocial work environment and mental health--a meta-analytic review.
AB  - OBJECTIVES: To clarify the associations between psychosocial work stressors and
      mental ill health, a meta-analysis of psychosocial work stressors and common
      mental disorders was undertaken using longitudinal studies identified through a
      systematic literature review. METHODS: The review used a standardized search
      strategy and strict inclusion and quality criteria in seven databases in 1994
      2005. Papers were identified from 24,939 citations covering social determinants
      of health, 50 relevant papers were identified, 38 fulfilled inclusion criteria,
      and 11 were suitable for a meta-analysis. The Comprehensive Meta-analysis
      Programme was used for decision authority, decision latitude, psychological
      demands, and work social support, components of the job-strain and iso-strain
      models, and the combination of effort and reward that makes up the effort-reward
      imbalance model and job insecurity. Cochran's Q statistic assessed the
      heterogeneity of the results, and the I2 statistic determined any inconsistency
      between studies. RESULTS: Job strain, low decision latitude, low social support,
      high psychological demands, effort-reward imbalance, and high job insecurity
      predicted common mental disorders despite the heterogeneity for psychological
      demands and social support among men. The strongest effects were found for job
      strain and effort-reward imbalance. CONCLUSIONS: This meta-analysis provides
      robust consistent evidence that (combinations of) high demands and low decision
      latitude and (combinations of) high efforts and low rewards are prospective risk
      factors for common mental disorders and suggests that the psychosocial work
      environment is important for mental health. The associations are not merely
      explained by response bias. The impact of work stressors on common mental
      disorders differs for women and men.

PMID- 17173202
TI  - Games researchers play--extreme-groups analysis and mediation analysis in
      longitudinal occupational health research.
AB  - OBJECTIVES: The study of causal processes using a longitudinal design is often
      hampered by two methodological problems. First, the lagged effects of a predictor
      variable on an outcome variable tend to be weak after control for a previous
      measure of this outcome. One approach that is advocated when effects are weak is
      to increase the extremeness of the study groups; this step often increases the
      significance and sizes of effects. Second, causal links are often mediated
      through third variables, and thus relatively complex mediational analyses are
      needed to understand the causal processes underlying particular associations. The
      present paper shows whether and when these two approaches are useful in
      longitudinal research. METHODS: The two approaches were evaluated using data from
      a three-wave study among 1251 newcomers from various Western countries (mean age
      20.6 years, 59% female). RESULTS: Although the significances and effect sizes
      indeed increased with increasing extremeness of the study groups, extreme-groups
      analysis in the context of a longitudinal design may grossly bias findings. Cross
      sectional applications of mediation analysis cannot provide evidence for any
      mediational model. Longitudinal models are better suited for examining mediation.
      CONCLUSIONS: Rather than using extreme-groups analysis to obtain significant
      effects across time, researchers should maximize the amount of change in their
      data by focusing on groups for which change can be expected. Especially
      multiphase longitudinal data sets offer good opportunities for analyzing
      mediation models.

PMID- 17173203
TI  - Work stress and health risk behavior.
AB  - This contribution discusses current knowledge of associations between
      psychosocial stress at work and health risk behavior, in particular cigarette
      smoking, alcohol consumption and overweight, by reviewing findings from major
      studies in the field published between 1989 and 2006. Psychosocial stress at work
      is measured by the demand-control model and the effort-reward imbalance model.
      Health risk behavior was analyzed in the broader context of a health-related
      Western lifestyle with socially and economically patterned practices of
      consumption. Overall, the review, based on 46 studies, only modestly supports the
      hypothesis of a consistent association between work stress and health risk
      behavior. The relatively strongest relationships have been found with regard to
      heavy alcohol consumption among men, overweight, and the co-manifestation of
      several risks. Suggestions for further research are given, and the need to reduce
      stressful experience in the framework of worksite health promotion programs is
      emphasized.

PMID- 17173204
TI  - Recovery as an explanatory mechanism in the relation between acute stress
      reactions and chronic health impairment.
AB  - This contribution aims at shedding light on the mechanisms that may underlie the
      relationship between acute reactions to stressful work characteristics and
      employee health in the long run. Recovery, a process of psychophysiological
      unwinding after effort expenditure, is considered a vital link in this
      relationship. This link is explained on the basis of assumptions from theories on
      effort, recovery, and sustained activation. It is argued that recovery after work
      (external recovery) is particularly necessitated when recovery opportunities
      during worktime (internal recovery) are insufficient. It is further argued that
      two conditions may impede the recovery process by sustaining physiological
      activation, prolonged exposure to work demands (working long hours) and cognitive
      stress-related processes (such as rumination). These theoretical assumptions are
      substantiated by empirical support from previous laboratory and field research.
      It is concluded that the chronic situation of sustained physiological activation
      and incomplete recovery is an important pathway to chronic health impairment.

PMID- 17173205
TI  - Psychosocial stress and impaired sleep.
AB  - This review demonstrates that stress is closely related to impaired sleep in
      cross-sectional studies. In particular, the anticipation of high demands or
      effort the next day seems important. Sleep recordings show that stress is
      associated with shortened sleep, fragmentation, and possibly a reduction in sleep
      stages 3 and 4. Shortened or disturbed sleep causes increases in levels of
      traditional stress markers (eg, cortisol) and may thus exacerbate the effects of
      stress. Much knowledge is still lacking, however, particularly about the effects
      of real-life work stress. The latter requires longitudinal studies in real-life
      situations.

PMID- 17173207
TI  - Job stress interventions and the organization of work.
AB  - Interventions that aim at improving health by changing the organization of work
      in terms of task characteristics, work conditions, and social aspects-have shown
      their potential, but results are mixed, and many studies do not use their
      methodological potential. It is proposed that interventions at the organizational
      level are likely to have a more diverse effect than at the individual level, as
      the number of subsystems, with potentially diverging interests, is larger. Even
      well-implemented interventions are not likely to lead to improvements in all
      parameters for all participants, and trade-offs have to be considered.
      Methodological improvement is necessary but should not only focus on design
      issues, but also on careful documentation and subgroup analyses. A combination of
      person-focused and organization-focused approaches is the most promising.
      Finally, evidence points to the limited utility of economic arguments for the
      acceptance of health promotion projects; the necessity of professional trust is
      therefore emphasized.

PMID- 17173206
TI  - Workhours in relation to work stress, recovery and health.
AB  - This paper aims at describing the associations between workhours and psychosocial
      work characteristics and reviews the health effects of workhours and the related
      pathways. The role of insufficient sleep as a possible common pathway from
      workhours and work stress to cardiovascular illness is discussed. Finally, the
      key possibilities for improving recovery and health through changes in workhours
      are identified. Night work and shift work are related to a wide range of health
      effects, the evidence for the risk of cardiovascular morbidity being the
      strongest. Insufficient or poor sleep, related to insufficient recovery, can be a
      common pathway from long workhours, shift work, and work stress to cardiovascular
      illness. The most promising worktime-related means for decreasing the
      psychosocial workload and negative health effects of workhours would be (i) to
      regulate overtime and excessive workhours, (ii) increase individual worktime
      control, and (iii) increase recovery from the introduction of sleep-promoting
      principles into shift rotation.

PMID- 17173208
TI  - Abdominal abscesses due to actinomycosis after laparoscopic cholecystectomy: case
      reports and review.
AB  - We describe 2 patients who presented to a health care facility with abdominal
      abscesses years after undergoing laparoscopic cholecystectomy that was
      complicated by gallstone spillage. In both patients, sample cultures yielded
      Actinomyces species and enteric organisms. In 1 patient, crystallographic
      analysis of abscess debris confirmed the presence of gallstones. Actinomyces
      species is a rare cause of abdominal abscesses that should be considered in this
      patient population.

PMID- 17173209
TI  - A case report and literature review of portal vein thrombosis associated with
      cytomegalovirus infection in immunocompetent patients.
AB  - We describe a young man with acute portal vein thrombosis (PVT) and
      cytomegalovirus (CMV) infection, and we review the literature regarding the
      association between PVT and CMV in immunocompetent patients. Published data
      suggest that CMV hepatitis and, possibly, other types of acute viral hepatitis
      could be a local risk factor for acute PVT.

PMID- 17173210
TI  - The relationship between previous fluoroquinolone use and levofloxacin resistance
      in Helicobacter pylori infection.
AB  - The relationship between prior fluoroquinolone use and levofloxacin resistance in
      Helicobacter pylori infection is unknown. Among 125 enrolled patients, 8.8% had
      H. pylori isolates that were resistant to levofloxacin. Levofloxacin resistance
      was associated with any prior fluoroquinolone use over the previous 10 years and
      with the total number of fluoroquinolone courses prescribed (P<.001).

PMID- 17173211
TI  - Candidemia in patients with ventricular assist devices.
AB  - During the period 1998-2004, candidemia developed in 7 of 117 ventricular assist
      device recipients at our hospital, and the associated mortality rate was 71%.
      Five cases of candidemia were due to Candida parapsilosis, and 2 were due to
      Candida albicans. Three of the 7 patients with ventricular assist device
      associated Candida bloodstream infections were cured, and the device was retained
      in 2 of the 3 patients.

PMID- 17173212
TI  - Infectious Diseases Society of America and the Society for Healthcare
      Epidemiology of America guidelines for developing an institutional program to
      enhance antimicrobial stewardship.

PMID- 17173213
TI  - Randomized controlled trial of chlorhexidine gluconate for washing, intranasal
      mupirocin, and rifampin and doxycycline versus no treatment for the eradication
      of methicillin-resistant Staphylococcus aureus colonization.
AB  - BACKGROUND: Eradication of methicillin-resistant Staphylococcus aureus (MRSA)
      carriage may reduce the risk of MRSA infection and prevent transmission of the
      organism to other patients. METHODS: To determine the efficacy of decolonization
      therapy, patients colonized with MRSA were randomized (3:1 allocation) to receive
      treatment (2% chlorhexidine gluconate washes and 2% mupirocin ointment
      intranasally, with oral rifampin and doxycycline for 7 days), or no treatment.
      Follow-up samples for MRSA culture were obtained from the nares, perineum, skin
      lesions, and catheter exit sites monthly for up to 8 months. The primary outcome
      measure was detection of MRSA at 3 months of follow-up. Univariate and
      multivariable analyses were performed to identify variables associated with
      treatment failure. RESULTS: Of 146 patients enrolled in the study, 112 patients
      (87 treated; 25 not treated) were followed up for at least 3 months. At 3 months
      of follow-up, 64 (74%) of those treated had culture results negative for MRSA,
      compared with 8 (32%) of those not treated (P=.0001). This difference remained
      significant at 8 months of follow-up, at which time, 54% of those treated had
      culture results negative for MRSA (chi2=64.4; P<.0001, by log-rank test). The
      results of the multivariable analysis indicated that having a mupirocin-resistant
      isolate at baseline was associated with treatment failure (relative risk, 9.4;
      95% confidence interval, 2.8-31.9; P=.0003), whereas decolonization therapy was
      protective (relative risk, 0.1; 95% confidence interval, 0.04-0.4; P=.0002).
      Mupirocin resistance emerged in only 5% of follow-up isolates. CONCLUSIONS:
      Treatment with topical mupirocin, chlorhexidine gluconate washes, oral rifampin,
      and doxycycline for 7 days was safe and effective in eradicating MRSA
      colonization in hospitalized patients for at least 3 months.

PMID- 17173214
TI  - Eradication or decolonization of methicillin-resistant Staphylococcus aureus
      carriage: what are we doing and why are we doing it?

PMID- 17173215
TI  - Use of vancomycin or first-generation cephalosporins for the treatment of
      hemodialysis-dependent patients with methicillin-susceptible Staphylococcus
      aureus bacteremia.
AB  - BACKGROUND: Because of its ease of dosing, vancomycin is commonly used to treat
      methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in patients
      undergoing long-term hemodialysis. Clinical outcomes resulting from such a
      therapeutic strategy have not been well defined. METHODS: We prospectively
      identified patients undergoing long-term hemodialysis who received a diagnosis of
      MSSA bacteremia. Clinical outcomes were grouped according to the predominant
      antibiotic received during their therapy (vancomycin or a first-generation
      cephalosporin [cefazolin]). Treatment failure (defined as death or recurrent
      infection) was determined at 12 weeks after the initial positive blood culture
      results. A multivariable analysis was used to adjust for confounders. RESULTS:
      During an 84-month period, 123 hemodialysis-dependent patients with MSSA
      bacteremia were identified. Patients receiving vancomycin (n=77) tended to be
      younger (51 vs. 57 years; P=.06) and had a lower rates of metastatic
      complications at presentation (11.7% vs. 36.7%; P=.001) than did those receiving
      cefazolin (n=46). The 2 groups were similar with regard to Acute Physiology and
      Chronic Health Evaluation II scores, comorbidities, source of infection, type of
      hemodialysis access, and access removal rates. Treatment failure was more common
      among patients receiving vancomycin (31.2% vs. 13%; P=.02). In the multivariable
      analysis, factors independently associated with treatment failure included
      vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15-13.45) and
      retention of the hemodialysis access (odds ratio, 4.99; 95% confidence interval,
      1.89-13.76). CONCLUSIONS: Hemodialysis-dependent patients with MSSA bacteremia
      treated with vancomycin are at a higher risk of experiencing treatment failure
      than are those receiving cefazolin. In the absence of patient specific
      circumstances (e.g., allergy to beta-lactams), vancomycin should not be continued
      beyond empirical therapy for hemodialysis-dependent patients with MSSA
      bacteremia.

PMID- 17173216
TI  - Lower clinical effectiveness of oseltamivir against influenza B contrasted with
      influenza A infection in children.
AB  - BACKGROUND: Recently, many Japanese physicians have claimed that oseltamivir is
      less effective in children with influenza B virus infection. This study assesses
      the effectiveness of oseltamivir against influenza A (H3N2) and influenza B in
      children on the basis of the duration of febrile illness. METHODS: We used
      oseltamivir to treat 127 children with influenza A (H3N2; mean age, 6.97 years
      [range, 1-15 years]) and 362 children with influenza B (mean age, 5.16 years
      [range, 1-15 years]) in outpatient clinics. The duration of fever after the start
      of oseltamivir therapy was compared in the influenza A group and the influenza B
      group. RESULTS: The mean duration of fever after the start of oseltamivir therapy
      was significantly greater in the influenza B group than in the influenza A (H3N2)
      group (2.18 days vs. 1.31 days, respectively; P<.001). The difference was marked
      in young children (1-5 years old; 2.37 days for the influenza B group vs. 1.42
      days for the influenza A group) but was not significant among older children (11
      15 years old). The 50% inhibitory concentration of oseltamivir against influenza
      B virus was 75.4+/-41.7 nmol/L and was substantially higher than that for type A
      (H3N2) virus (0.3+/-0.1 nmol/L). Only 3 (1.6%) of 192 influenza B viruses were
      resistant to oseltamivir. CONCLUSIONS: Oseltamivir is much less effective against
      influenza B virus infection in young children, probably because of the low
      sensitivity of influenza B viruses to oseltamivir. The effectiveness of
      oseltamivir against influenza B is influenced by age and host immunity. A few
      oseltamivir-resistant influenza B strains were isolated before the start of
      oseltamivir therapy.

PMID- 17173217
TI  - Does oseltamivir work against influenza B?

PMID- 17173218
TI  - Opportunistic infections in 547 organ transplant recipients receiving
      alemtuzumab, a humanized monoclonal CD-52 antibody.
AB  - BACKGROUND: Alemtuzumab is being increasingly used for the prevention and/or
      treatment of acute allograft rejection in organ transplant recipients. We
      assessed the risks of infection in, to our knowledge, the largest cohort and
      broadest range of organ transplant recipients yet reported to have received
      alemtuzumab. METHODS: All patients who received alemtuzumab from September 2002
      through March 2004, either as induction therapy at the time of transplantation or
      for the treatment of rejection, were evaluated for the development of an
      opportunistic infection (OI) until death or for 12 months after receipt of the
      last dose of alemtuzumab. RESULTS: A total of 547 recipients were included, 65%
      of whom received alemtuzumab for induction therapy only. Overall, 56 recipients
      (10%) developed 62 OIs, including cytomegalovirus disease (n = 16), BK virus
      infection (n=12), posttransplantation lymphoproliferative disease (n=5), human
      herpesvirus 6 infection (n=1), parvovirus infection (n=1), esophageal candidiasis
      (n=12), cryptococcosis (n=2), invasive mold infection (n=4), Nocardia infection
      (n=4), mycobacterial infection (n=3), Balamuthia mandrillaris infection (n=1),
      and toxoplasmosis (n=1). Patients who received alemtuzumab for induction therapy
      were significantly less likely to develop an OI, compared with patients who
      received alemtuzumab for rejection therapy (4.5% vs. 21%; P<.001). Independent
      predictors of the development of an OI were administration of alemtuzumab for
      rejection therapy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.8-6.8;
      P<.001), allograft failure (OR, 2.1; 95% CI, 1.1-4.4; P=.04), and receipt of a
      lung transplant (OR, 3.7; 95% CI, 1.7-8.0; P=.001) or an intestinal transplant
      (OR, 8.3; 95% CI, 3.5-19.5; P<.001). CONCLUSIONS: Patients who received
      alemtuzumab for the treatment of allograft rejection were significantly more
      likely to develop an OI, compared with patients who received alemtuzumab for
      induction therapy only. Such data have implications for new antimicrobial
      prophylactic strategies.

PMID- 17173219
TI  - A randomized trial of the duration of therapy with metronidazole plus or minus
      azithromycin for treatment of symptomatic bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis (BV) is the most common cause of vaginitis
      worldwide. Currently recommended treatments have poor efficacy and are associated
      with high rates of BV recurrence. We examined whether a longer duration of
      treatment with metronidazole or combination therapy with metronidazole and
      azithromycin would enhance the cure rates for BV. In addition, we examined
      factors other than drug therapy associated with cure. METHODS: Women with
      symptomatic BV (defined by a modified Amsel criteria) were enrolled in a 4-arm
      study that compared metronidazole for 7 days versus 14 days, plus or minus
      azithromycin on days 1 and 3. Data regarding interim behaviors were also
      obtained, as were vaginal specimens for Gram staining. RESULTS: At the first
      follow-up visit (7 days after the completion of therapy), there was a significant
      difference in cure rates among patients who received 7 days of metronidazole
      therapy, compared with those who received 14 days of therapy, combined across
      azithromycin therapy (P=.0003). There was no effect associated with azithromycin
      therapy. There were no differences in cure rates between any of the treatment
      groups at 21 days after completion of therapy. Abstinence or protected sex,
      refraining from douching, and a lower baseline Nugent score for the vaginal Gram
      stain were all significantly associated with cure. CONCLUSIONS: Cure rates for BV
      were significantly improved by 14 days of metronidazole treatment (compared with
      7 days of treatment), but the effects were not sustained, suggesting that relapse
      or reinfection occurred. Combination therapy with the addition of azithromycin
      had no benefit. Lower baseline Nugent scores--presumably reflecting less complex
      vaginal flora--were significantly associated with cure, as was refraining from
      unprotected sex and from douching.

PMID- 17173220
TI  - Bacterial vaginosis: resistance, recurrence, and/or reinfection?

PMID- 17173221
TI  - A large, travel-associated outbreak of legionellosis among hotel guests: utility
      of the urine antigen assay in confirming Pontiac fever.
AB  - BACKGROUND: During March 2004, a large outbreak of legionnaires disease and
      Pontiac fever occurred among hotel guests in Oklahoma. An investigation was
      conducted to identify the source and evaluate the utility of the Legionella urine
      antigen assay and serologic testing for the identification of Pontiac fever.
      METHODS: A retrospective cohort investigation of hotel guests and employees and
      an environmental evaluation were performed. Participants were interviewed, and
      clinical specimens were collected from consenting individuals. RESULTS: Six cases
      of legionnaires disease and 101 cases of Pontiac fever were identified. Exposure
      to the indoor pool and hot tub area was associated with legionellosis (relative
      risk, 4.4; 95% confidence interval, 2.8-6.9). Specimens from the pool and hot tub
      tested positive for Legionella pneumophila serogroup 1 by polymerase chain
      reaction. For Pontiac fever, the sensitivity and positive predictive value were
      35.7% and 100%, respectively, for the urine antigen assay, and 46.4% and 90%,
      respectively, for serologic testing. The specificity and negative predictive
      value were 100% and 47.8%, respectively, for the urine antigen assay, and 89.3%
      and 45.5%, respectively, for serologic testing. CONCLUSIONS: Urine antigen
      testing, with or without serologic testing, can be used to confirm outbreak
      associated cases of Pontiac fever caused by L. pneumophila serogroup 1.

PMID- 17173222
TI  - Urine antigen tests positive for Pontiac fever: implications for diagnosis and
      pathogenesis.

PMID- 17173223
TI  - Role of sex, age, previous valve lesion, and pregnancy in the clinical expression
      and outcome of Q fever after a large outbreak.
AB  - BACKGROUND: Q fever is a zoonosis caused by Coxiella burnetii. After a large
      outbreak occurred in the Chamonix Valley in the French Alps in 2002, an extensive
      surveillance was conducted, to describe the variations in the clinical expression
      of acute Q fever according to host factors, as well as to monitor the risk of
      evolution of acute Q fever to chronic Q fever in patients at risk. METHODS: Three
      groups of patients with risk factors for evolution of acute Q fever to chronic Q
      fever were considered: 376 pregnant women, 19 immunocompromised patients, and 91
      patients with valvular or vascular abnormalities. A group of 578 people without
      risk factors for evolution of acute Q fever to chronic Q fever was also tested.
      Diagnosis of Q fever was based on serologic testing by immunofluorescence assay.
      RESULTS: Between 30 August 2002 and 31 July 2003, a total of 1946 serum samples
      obtained from 1064 persons were tested. A total of 101 patients (9.3%) had acute
      Q fever diagnosed, and 5 patients (0.5%) had chronic Q fever diagnosed. A
      diagnosis of acute Q fever was established for 11 pregnant women (2.6% of 379
      pregnancies), 5 patients with valvular disease (5.5%), and 85 people without risk
      factors (14.7%) (71 [27.9%] of 254 symptomatic patients and 14 [4.3%] of 324
      asymptomatic patients). A new pregnancy in a woman with negative results of
      serologic tests for Q fever exposes the woman to a new risk for acute Q fever
      able to evolve to chronic Q fever. The rates of clinical expression were 90.6% in
      adult men, 75% in adult women, and 33.3% in children, and they were significantly
      lower (9.1%) in pregnant women. Evolution to chronic Q fever was observed in 5
      patients. CONCLUSION: This study emphasizes the importance of active surveillance
      in postepidemic conditions, especially among patients at risk, as well as the
      importance of systematic serologic testing during pregnancy.

PMID- 17173224
TI  - A portrait of the geographic dissemination of the Clostridium difficile North
      American pulsed-field type 1 strain and the epidemiology of C. difficile
      associated disease in Quebec.
AB  - BACKGROUND: An increase in the incidence and severity of Clostridium difficile
      associated disease in Quebec and the United States has been associated with a
      hypervirulent strain referred to as North American pulsed-field type 1
      (NAP1)/027. METHODS: In 2005, a prospective study was conducted in 88 Quebec
      hospitals, and 478 consecutive nosocomial isolates of C. difficile were obtained.
      The isolates were subjected to pulsed-field gel electrophoresis (PFGE) typing,
      antimicrobial susceptibility testing, and detection of binary toxin genes and
      tcdC gene deletion. Data on patient age and occurrence of complications were
      collected. RESULTS: PFGE typing of 478 isolates of C. difficile yielded 61 PFGE
      profiles. Pulsovars A (57%), B (10%), and B1 (8%) were predominant. The PFGE
      profile of pulsovar A was identical to that of strain NAP1. It showed 67%
      relatedness with 15 other PFGE patterns, among which 11 had both binary toxin
      genes and a partial tcdC deletion but different antibiotic susceptibility
      profiles. Pulsovars B and B1 were identical to strain NAP2/ribotype 001. In
      hospitals showing a predominant clonal A or B-B1 PFGE pattern, incidence of C.
      difficile-associated disease was 2 and 1.3 times higher, respectively, than in
      hospitals without any predominant clonal PFGE pattern. Severe disease was twice
      as frequent among patients with strains possessing binary toxin genes and tcdC
      deletion than among patients with strains lacking these virulence factors.
      CONCLUSIONS: This study helped to quantify the impact of strain NAP1 on the
      incidence and severity of C. difficile-associated disease in Quebec in 2005. The
      identification of the geographic dissemination of this predominant strain may
      help to focus regional infection-control efforts.

PMID- 17173225
TI  - Randomized controlled multicenter trial of aerosolized ribavirin for respiratory
      syncytial virus upper respiratory tract infection in hematopoietic cell
      transplant recipients.
AB  - BACKGROUND: Respiratory syncytial virus infection of the upper airways may
      progress to fatal pneumonia in hematopoietic cell transplant recipients. The
      safety and efficacy of aerosolized ribavirin in preventing disease progression is
      unknown. METHODS: In a multicenter prospective trial, hematopoietic cell
      transplant recipients with respiratory syncytial virus infection of the upper
      airways were randomized to receive ribavirin (2 g 3 times daily) or supportive
      care for 10 days. The primary end point was progression to radiographically
      proven pneumonia. Secondary end points included virologically proven respiratory
      syncytial virus pneumonia, viral load changes, and safety. RESULTS: Fourteen
      patients were randomized to 1 of 2 treatment arms. The trial was discontinued
      after 5 years because of slow accrual. Pneumonia at 1 month after randomization
      occurred in 1 of 9 patients who received ribavirin and in 2 of 5 patients who
      received supportive care (P=.51); virologically proven respiratory syncytial
      virus pneumonia occurred in 0 of 9 and 2 of 5 patients, respectively (P=.11). At
      10 days after randomization, the average viral load decreased by 0.75 log10
      copies/mL in ribavirin recipients, compared with a viral load increase of 1.26
      log10 copies/mL in untreated patients (P=.07). No discontinuations of ribavirin
      therapy because of adverse effects occurred during 84 drug administrations. Rates
      of adverse events were similar in both groups. CONCLUSIONS: Preemptive
      aerosolized ribavirin treatment appeared to be safe, and trends of decreasing
      viral load over time were observed. However, proof of efficacy remains elusive in
      hematopoietic cell transplant recipients.

PMID- 17173227
TI  - The role of microbes in Crohn's disease.
AB  - Despite decades of research, the etiology of Crohn's disease (CD) remains
      unknown. Its pathogenesis may involve a complex interplay between host genetics,
      immune dysfunction, and microbial or environmental factors. Microorganisms,
      including pathogens and members of the indigenous microbiota, may initiate or
      propagate the inflammatory process in CD. The pathogenesis of CD has been
      difficult to study, owing to the broad spectrum of typically nonspecific clinical
      manifestations, the complexity of environmental and genetic factors, the lack of
      an accurate model of disease, and the limitations of microbiological methods. A
      more useful and relevant paradigm for the etiology of CD might be based on the
      idea of a pathogenic microbial community profile and might emphasize the role of
      interactive sets of microbes, rather than the role of individual organisms. We
      review how microbes may participate in the pathogenesis of CD and how they may
      inappropriately activate the mucosal immune system in genetically predisposed
      individuals.

PMID- 17173226
TI  - Levels of vancomycin in cerebrospinal fluid of adult patients receiving
      adjunctive corticosteroids to treat pneumococcal meningitis: a prospective
      multicenter observational study.
AB  - BACKGROUND: Evidence from a recent randomized controlled trial suggests that
      dexamethasone as adjunct therapy in adult pneumococcal meningitis reduces
      mortality and neurological sequelae. However, adding dexamethasone has the
      potential to reduce penetration of vancomycin into the cerebrospinal fluid (CSF).
      We sought to determine concentrations of vancomycin in serum and CSF of patients
      with suspected or proven pneumococcal meningitis receiving dexamethasone to
      assess the penetration of vancomycin into the CSF during steroid therapy.
      METHODS: In an observational open multicenter study, adult patients admitted to
      the intensive care unit because of suspected pneumococcal meningitis received
      recommended treatment for pneumococcal meningitis, comprising intravenous
      cefotaxime (200 mg per kg of body weight per day), vancomycin (administered as
      continuous infusion of 60 mg per kg of body weight per day after a loading dose
      of 15 mg per kg of body weight), and adjunctive therapy with dexamethasone (10 mg
      every 6 h). Vancomycin levels in CSF were measured on day 2 or day 3 of therapy
      and were correlated with protein levels in CSF and vancomycin levels in serum
      (determined at the same time as levels in CSF). RESULTS: Fourteen patients were
      included. Thirteen had proven pneumococcal meningitis; 1 patient, initially
      suspected of having pneumococcal meningitis, was finally determined to have
      meningitis due to Neisseria meningitidis. Mean levels of vancomycin in serum and
      CSF were 25.2 and 7.2 mg/L, respectively, and were positively correlated (r=0.6;
      P=.025). A positive correlation was also found between the ratio of vancomycin in
      CSF to vancomycin in serum and the level of protein in CSF (r=0.66; P=.01).
      CONCLUSIONS: Appropriate concentrations of vancomycin in CSF may be obtained even
      when concomitant steroids are used. Dexamethasone can, therefore, be used without
      fear of impeding vancomycin penetration into the CSF of patients with
      pneumococcal meningitis, provided that vancomycin dosage is adequate. This study
      is registered at http://www.ClinicalTrials.gov/ (registration number
      NCT00162578).

PMID- 17173228
TI  - Hospital-acquired legionnaires disease in a university hospital: impact of the
      copper-silver ionization system.
AB  - We evaluated the impact of the copper-silver ionization system in a hospital
      where hyperendemic nosocomial legionellosis and was present and all previous
      disinfection measures had failed. After implementation of the copper-silver
      ionization system, environmental colonization with Legionella species decreased
      significantly, and the incidence of nosocomial legionellosis decreased
      dramatically, from 2.45 to 0.18 cases per 1000 patient discharges.

PMID- 17173229
TI  - A pertussis outbreak associated with social isolation among elderly nuns in a
      convent.
AB  - The pertussis incidence during an outbreak in a convent in The Netherlands in
      1992 was higher among 75 retired (unvaccinated) nuns (60%) than among 24 staff
      members (8%) and was higher among 9 nuns with only a convent career (100%) than
      among 66 nuns who had a career outside of the convent (55%). The pertussis
      incidence increased with duration of social isolation but not with age.

PMID- 17173230
TI  - An elderly man receiving hemodialysis who had diarrhea, weight loss, and liver
      mass.

PMID- 17173231
TI  - Use of prediction markets to forecast infectious disease activity.
AB  - Prediction markets have accurately forecasted the outcomes of a wide range of
      future events, including sales of computer printers, elections, and the Federal
      Reserve's decisions about interest rates. We propose that prediction markets may
      be useful for tracking and forecasting emerging infectious diseases, such as
      severe acute respiratory syndrome and avian influenza, by aggregating expert
      opinion quickly, accurately, and inexpensively. Data from a pilot study in the
      state of Iowa suggest that these markets can accurately predict statewide
      seasonal influenza activity 2-4 weeks in advance by using clinical data
      volunteered from participating health care workers. Information revealed by
      prediction markets may help to inform treatment, prevention, and policy
      decisions. Also, these markets could help to refine existing surveillance
      systems.

PMID- 17173232
TI  - New consensus guidelines from the Clinical and Laboratory Standards Institute for
      antimicrobial susceptibility testing of infrequently isolated or fastidious
      bacteria.
AB  - The Clinical and Laboratory Standards Institute (CLSI) recently published a new
      laboratory guideline for antimicrobial susceptibility testing of infrequently
      encountered or fastidious bacteria not covered in previous CLSI publications. The
      organisms include Aeromonas species, Bacillus species, and Vibrio species that
      may cause infections following environmental exposure. Fastidious organisms that
      may cause endocarditis or medical device infections include Abiotrophia and
      Granulicatella species; coryneform bacteria; Haemophilus, Actinobacillus,
      Cardiobacterium, Eikenella, and Kingella group gram-negative rods; and the
      instrinsically vancomycin-resistant gram-positive organisms Erysipelothrix,
      Lactobacillus, Leuconostoc, and Pediococcus species. Organisms not previously
      covered in depth in CLSI guidelines include Branhamella catarrhalis,
      Campylobacter jejuni, Campylobacter coli, Listeria species, and Pasteurella
      species. Clinically important drug resistance has been reported for each of these
      organisms. The guidelines provide recommendations for when it may be important to
      test these organisms, how standard methods may be easily adapted for testing, and
      appropriate interpretive criteria for results. Communication with infectious
      diseases clinicians prior to performing such testing is emphasized.

PMID- 17173233
TI  - Mortality among participants in the Multicenter AIDS Cohort Study and the Women's
      Interagency HIV Study.
AB  - BACKGROUND: Many studies that have reported decreases in human immunodeficiency
      virus (HIV)-related mortality since the advent of highly active antiretroviral
      therapy (HAART) have also reported steady increases in non-HIV-related mortality
      over the same time periods. We examined temporal trends and risk factors for
      accident- and injury-related mortality among HIV-infected and -uninfected
      participants in the Women's Interagency HIV Study (WIHS) and the Multicenter AIDS
      Cohort Study (MACS). METHODS: Information on causes of death was recorded for all
      participants in the MACS and WIHS cohort studies who died, and causes of death
      were categorized as accident- or injury-related deaths or not. Mortality rates
      were calculated by time periods, prior to the widespread use of HAART (before
      1997) and after (1997-2002), and risk factors. RESULTS: Cause of death
      information was available for 619 women in the WIHS who died (during the period
      1994-2002) and 1830 men in the MACS who died (during the period 1984-2002). The
      death rates were higher for accident- or injury-related mortality in the WIHS
      (2.96 deaths per 1000 person-years for the HIV-infected group and 2.96 per 1000
      person-years for the HIV-uninfected group), compared with the participants in
      MACS (0.79 deaths per 1000 person-years for the HIV-infected group and 0.63 per
      1000 person-years for the HIV-uninfected group). In the final multivariate
      analysis, the following factors were associated with significantly higher risk in
      men: higher education, depressive symptoms, and a greater number of sex partners.
      Among women, the significant risk factors for death were decreased CD4+ T cell
      count, unemployment, higher alcohol use, and injection drug use. CONCLUSION: The
      characteristics of the men in the MACS who died and women in the WIHS who died
      differ, as do the risk factors for mortality. These results characterize
      important target groups for interventions to reduce accident- and injury-related
      deaths.

PMID- 17173234
TI  - Weight and body shape changes in a treatment-naive population after 6 months of
      nevirapine-based generic highly active antiretroviral therapy in South India.
AB  - BACKGROUND: The nutritional and body shape response after the initiation of
      highly active antiretroviral therapy (HAART) in resource-limited environments has
      not been documented. In this environment, nutritional compromise is a common
      complication of human immunodeficiency virus (HIV) infection. METHODS: We
      conducted a prospective study of 190 HIV-infected patients who initiated a
      nevirapine-based HAART regimen. CD4+ T cell count, body weight, body mass index,
      anthropometry, and bioelectrical impedance data were collected prior to
      initiation of therapy and after 6 months of therapy. RESULTS: The mean age of
      participants was 35 years, 85% of participants were male, and 59% received
      stavudine as 1 of the nucleosides in their initial HAART regimen. The members of
      the cohort were malnourished before the initiation of therapy and had a mean body
      mass index of 20.1 (calculated as weight in kilograms divided by the square of
      height in meters). Overall, body weight increased a mean of 2.8 kg (range, -12.5
      to 22.5 kg), and CD4+ T cell counts increased by a mean of 140 cells/mm3.
      Patients were stratified into those who lost weight (loss of >1 kg, 22%; n=41),
      those whose weight remained stable (19%; n=37), and those who gained weight (gain
      of >1 kg, 59%; n=112). Patients in all groups retained body shape symmetry and
      experienced no change in waist-to-hip ratio or regional body shape by
      anthropometry. CONCLUSIONS: The group that lost weight and the group whose weight
      remained stable experienced significant CD4+ T cell count increases at 6 months.
      Although the majority of HIV-infected patients who received nevirapine-based
      HAART gained weight, there were participants who lost weight despite initiating
      their first HAART therapy.

PMID- 17173235
TI  - Epidemiologic investigation of a cluster of workplace HIV infections in the adult
      film industry: Los Angeles, California, 2004.
AB  - BACKGROUND: Adult film production is a legal, multibillion dollar industry in
      California. In response to reports of human immunodeficiency virus (HIV)
      transmission by an adult film worker, we sought to determine the extent of HIV
      infection among exposed workers and to identify means of improving worker safety.
      METHODS: The Los Angeles County Department of Health Services initiated an
      outbreak investigation that included interviews of infected workers to elicit
      information about recent sex partners, review of the testing agency's medical
      records and laboratory results, molecular analysis of HIV isolates from the 4
      infected workers, and a risk assessment of HIV transmission in the adult film
      industry. RESULTS: Many adult film workers participate in a monthly program of
      screening for HIV infection by means of polymerase chain reaction-based
      technology to detect HIV DNA in blood. A male performer tested negative for HIV
      on 12 February 2004 and 17 March 2004, then tested positive for HIV on 9 April
      2004. During the period between the negative test results, he experienced a
      flulike illness after performing unprotected vaginal and anal intercourse for an
      adult film produced outside the United States by a US company. After returning to
      California, he performed unprotected sex acts for adult films with 13 female
      partners who had all tested negative for HIV in the preceding 30 days; 3
      subsequently tested positive for HIV (a 23% attack rate). Contact tracing
      identified no reasonable sources of infection other than the male index patient.
      CONCLUSION: Although current testing methods may shorten the window period to
      diagnosis of new HIV infection, they fail to prevent occupational acquisition of
      HIV in this setting. A California Occupational Safety and Health Administration
      approved written health and safety program that emphasizes primary prevention is
      needed for this industry.

PMID- 17173237
TI  - What length of follow-up in patients with HIV and hepatitis C virus coinfection
      is necessary to consider the level of transaminases to be "persistently normal"?

PMID- 17173238
TI  - Treatment of mucosal leishmaniasis with a lipid formulation of amphotericin B.

PMID- 17173239
TI  - The kidney and hypertension: over 70 years of research.
AB  - The crucial role of the kidneys in regulation of systemic blood pressure has been
      known for more than 70 years. A multitude of studies have described the
      regulatory mechanisms behind this interaction, and elucidate why kidney disease
      is such a rampant and difficult form of secondary hypertension. Historically,
      renal hypertension has primarily been described as derangements of the renin
      angiotensin-aldosterone system (RAAS), and salt and volume retention. Renally
      mediated hypertension involves the activation of RAAS leading to angiotensin II
      mediated vaso-constriction, and aldosterone-mediated salt retention. The
      increased sodium retention and volume expansion seen in kidney disease is
      accompanied by a failure to autoregulate the peripheral vasculature, leading to
      hypertension. An-giotensin II and aldosterone also cause increased inflammation
      and endothelial dysfunction, and volume retention leads to the elaboration of
      ouabain-like compounds that contribute to increased total peripheral resistance.
      More recently, studies have shown that activation of renal afferent pathways
      connecting with specific brain nuclei involved in the noradrenergic control of
      blood pressure appears to play a substantial role. This article will review the
      classic pa-radigms, as well as new and emerging paradigms linking the kidney with
      blood pressure.

PMID- 17173240
TI  - Cellular and molecular biology of membranous nephropathy.
AB  - There have been dramatic increases in the understanding of the molecular
      mechanisms involved in membranous nephropathy (MN) over the past 2 decades. Most
      of these have come directly from studies carried out in the Heymann nephritis
      models of MN in rats, which closely simulate the clinical and pathologic features
      of the human disease. Once considered a prototypical example of circulating
      immune complex trapping in glomeruli, we now recognize that MN develops, in both
      the rat and man, consequent to an autoimmune process involving antibodies
      directed to antigens on the foot processes of podocytes that form subepithelial
      immune deposits. Proteinuria is a consequence of sublytic complement C5b-9 attack
      on podocytes. The podocyte response to sublytic C5b-9 includes up-regulated
      expression of genes for production of oxidants, proteases, prostanoids, growth
      factors, CTGF, transforming growth factor (TGF) and TGF receptors leading to
      overproduction of extracellular matrix components that result in 'spike'
      formations. Other podocyte changes including detachment, apoptosis and
      alterations in cell cycle regulatory proteins favoring hypertrophy over
      proliferation also contribute to proteinuria and to development of glomerular
      sclerosis. Finally, progression of chronic proteinuric MN to chronic kidney
      disease (CKD) and renal failure likely results in part from additional effects of
      sublytic C5b-9 on proximal tubular epithelial cells, resulting in interstitial
      inflammation and fibrosis with a fall in glomerular filtration rate (GFR).
      Expanded understanding of the molecular pathophysiology of MN has important
      implications for monitoring disease activity, predicting disease course and
      designing new approaches to therapy for this common glomerular disease.

PMID- 17173241
TI  - Adult stem cells and renal repair.
AB  - During renal injury, stem cells derived from the circulation as well as resident
      stem cells may contribute to renal repair. Preliminary studies suggest the
      possibility to exploit this regenerative potential of stem cells for therapeutic
      purposes. This may be achieved either by administration of ex vivo expanded
      populations of mesenchymal stem cell or by strategies aimed to expand and
      differentiate local progenitor/stem cell populations. There is a general
      agreement that the beneficial effect of ex vivo expanded stem cell administration
      in acute renal injury is due to the generation of an environment that favours
      proliferation of dedifferentiated epithelial cells surviving the injury or of
      resident stem cells.

PMID- 17173242
TI  - Structural and functional properties of proteasomes purified from the human
      kidney.
AB  - BACKGROUND: Proteasomes are 'proteolytic machineries' implicated in many cellular
      functions, including protein turnover, inflammatory response and
      immunosurveillance. They exist in various forms sharing the same catalytic core -
      the 20S proteasome. This core consists of 28 subunits codified by 14 different
      genes, 3 of which - beta 1, beta 2 and beta 5 - are catalytically active and show
      peptidyl-glutamyl peptide hydrolyzing (PGPH), trypsin-like and chymo-trypsin-like
      activities, respectively. Under IFN- delta and TNF- alfa stimuli, the 3 active
      constitutive subunits are replaced by the corresponding ones - i.e., LMP2, MECL
      1, LMP7 - known as inducible subunits, thus resulting in the constitution of the
      'immunoproteasome' that is specifically implicated in MHC class I-presented
      peptide generation. This process is enhanced when the proteasome is associated
      with the polymeric protein 11S regulator/PA28 made up of 4 alfa and 3 beta
      subunits. METHODS: The 20S proteasome was purified from post mortem specimens of
      human kidney cortex by chromatographic and ultracentrifugation techniques. It was
      then characterized on the basis of (i) multicatalytic activity evaluated using
      specific fluorogenic peptides, (ii) electrophoretic mobility on non-denaturating
      polyacrylamide gels followed by in-gel visualization by fluorogenic peptide
      overlaying and Coomassie blue staining and (iii) subunit composition as
      ascertained by SDS-PAGE and 2-dimensional electrophoresis followed by silver
      staining or Western immunoblotting using specific antibodies against the
      proteasome subunits. The 20S proteasome was also studied for its association with
      the 11S regulator by Western immunoblotting using an antibody to the regulator
      alfa subuniT. RESULTS: T he purified proteasome was shown to have PGPH, trypsin
      like and chymotrypsin-like activities. Furthermore, it incorporated the inducible
      subunits and was associated with the 11S regulator. CONCLUSIONS: The features we
      observed make renal cells susceptible to an over-expression of inflammatory
      response to immunological challenges.

PMID- 17173243
TI  - Comparative cytotoxicity of high-osmolar and low-osmolar contrast media on HKCs
      in vitro.
AB  - BACKGROUND: Radiocontrast-induced nephropathy is a clinically important
      complication of intravascularly applied radiocontrast media. A predominant toxic
      effect of contrast media on renal tubules has been shown in previous clinical
      trials and animal experiments. Bax and Bcl-2 are members of the Bcl-2 family.
      Caspases are a family of cell death proteases, caspase-3 is one of the key
      executioners of apoptosis. In this study, we evaluated the cytotoxicity of high
      osmolar contrast media (HOCM; diatrizoate) and low-osmolar contrast media (LOCM;
      iohexol) on human renal tubular epithelial cells (HKCs), and determined the
      regulatory roles of Bax/Bcl-2 and caspase-3 on apoptosis induced by contrast
      media (CM) in HKCs. METHODS: An HKC line was used. Experiments were divided into
      7 groups: the HOCM group with iodine 111 mg/mL, HOCM group with iodine 74 mg/mL,
      LOCM group with iodine 111 mg/mL, LOCM group with iodine 74 mg/mL, mannitol high
      osmolar control group, mannitol low-osmolar control group and a culture media
      control group . The cytotoxicity of HOCM and LOCM were evaluated by cell
      proliferation and viability assay (MTT assay) and lactate dehydrogenase (LDH)
      release. Apoptosis were assessed by Hochest 33258 fluorescence-stained cytospins,
      TUNEL staining, DNA agarose gel electrophoresis, electron microscope and flow
      cytometric DNA analysis. The protein ex-pression of Bax/Bcl-2 was determined by
      Western blot analysis, and caspase-3 activity was also determined by the fluo
      rometric method. RESULTS: Compared with the control group, LDH levels increased
      significantly (p<0.05) and cell viability decreased in cells treated with HOCM or
      LOCM (p<0.05) in an osmotic pressure-, iodinated ion- and time-dependent manner;
      in the HOCM groups, diatrizoate induced cultured HKC apoptosis. In the LOCM
      groups, iohexol did not induce apoptosis. Compared with equal osmotic pressure
      mannitol, apoptosis increased in HKCs incubated with diatrizoate (p<0.05).
      Bax/Bcl-2 production and caspase-3 activity were up-regulated in cultured HKCs
      treated with HOCM iodine 74 or 111 mg/mL meglumine diatrizoate. CONCLUSIONS: Both
      HOCM and LOCM had toxic effects on HKCs, HOCM was more cytotoxic than LOCM; HOCM
      induced cultured HKC apoptosis while LOCM did not induce cultured HKC apoptosis
      in the indicated concentrations. The regulation of apoptosis induced by HOCM in
      HKCs may be regulated by Bax/Bcl-2 and caspase-3.

PMID- 17173244
TI  - Long-term treatment with an ACE inhibitor or an AT1 antagonist avoids
      hypertension-induced inflammation in the kidney.
AB  - BACKGROUND: Hypertension causes an inflammatory response in the kidney. Many
      studies have demonstrated that activation of the renal renin-angiotensin system,
      and therefore an increase in local angiotensin II (AngII) production,
      participates in the renal inflammatory cell recruitment. Our aim was to
      investigate the role of AngII blockade in hypertension-induced inflammatory
      response. METHODS: To replicate chronic hypertension with renal disease, we used
      a model of spontaneously hypertensive rats with unilateral nephrectomy (UNX-SHR).
      These animals were studied for 48 weeks. We investigated the effect of long-term
      treatment with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin
      II type 1 (AT1 ) antagonist, 2 strategies currently used in humans, on renal
      proinflammatory parameters. RESULTS: UNX-SHR rats presented elevated renal
      inflammatory cell infiltration and up-regulation of proinflammatory factors,
      including activation of nuclear factor chi B (NF-chi B) and related genes. Both
      ACE inhibition and AT 1 blockade decreased the number of inflammatory cells as
      well as the up-regulation of proinflammatory factors in the kidney. CONCLUSIONS:
      These results suggest that either AT 1 blockade or ACE inhibition can stop the
      renal inflammatory process in chronic hypertension-associated inflammatory
      response.

PMID- 17173245
TI  - Paraoxonase gene polymorphism and serum activity in progressive IgA nephropathy.
AB  - BACKGROUND: HDL-associated paraoxonase (PON1) reduces oxidation of lipids in LDL,
      and activity is inversely related to coronary heart disease risk with a
      beneficial effect on the development of atherosclerosis. Risk factors associated
      with atherosclerosis, such as hypertension, dyslipidemia and smoking, also
      promote the progression of chronic glomerulonephritides which may therefore be
      associated with perturbations in PON1 activity. METHODS: We performed a genetic
      association study in patients with IgA nephropathy (IgAN) (n=115) compared with
      control subjects (n=118). The aim was to test whether polymorphisms in the PON1
      coding region (Q192R and L55M) and its promoter (-108C/T and -162A/G) are
      associated with either IgAN or with the progression. We measured serum
      paraoxonase activity in 60 out of 115 patients. All patients had been followed up
      for more than 4 years. RESULTS: There were no differences in the genotype
      frequency at 3 of the polymorphic sites (Q192R, L55M and -108C/T) between the
      patients and controls. However, the frequency distribution at -162 position (A/G)
      was significantly diffe-rent in IgAN (p=0.028, chi-square test) with a higher
      frequency of the heterozygote (0.017, Fisher exact test [FE]; odds ratio [OR] =
      1.99; 95% confidence interval [95% CI], 1.14-3.47). Although there were no
      differences in the genotype frequency at 3 of the polymorphic sites (Q192R, L55M
      and -162C/T) between the patients with progressive IgA and the nonprogressive
      patients, we found that the frequency of the C allele for the -108C/T
      polymorphism was elevated in those patients with nonprogressive disease (n=85)
      compared with those with progressive disease (n=30) (61% vs. 47%; p=0.070, FE;
      OR=1.75, 95% CI, 0.97-3.18). Furthermore, PON1 activity was significantly higher
      in nonprogressive patients compared with progressors (206 +/- 71 vs. 136 +/- 48;
      p<0.001), and activity significantly correlated with 1/serum creatinine (SCr)
      (p<0.001; r=0.38). CONCLUSIONS: The results of this study suggest that in IgAN,
      lower PON1 activity may be associated with the deterioration of kidney function.
      This could be due to variable expression of the PON1 gene, or a functional effect
      of the gene product.

PMID- 17173246
TI  - Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility
      in patients on peritoneal dialysis and hemodialysis.
AB  - BACKGROUND: Several medications have been tested with the aim of decreasing
      oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The
      aim of the present study was to assess the influence of vitamin E therapy on
      oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis
      (HD) and peritoneal dialysis (PD). METHODS: This was a placebo-controlled study.
      The study was performed on 34 HD patients, 13 PD patients and 22 healthy
      volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into
      2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300
      mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid
      peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were
      examined before and after treatment. RESULTS: Before the treatment, the levels of
      EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and
      erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001)
      were significantly higher in the healthy group than PD and HD groups. Serum
      vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF
      decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA
      values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD
      treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/-
      0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment
      (p=0.021). CONCLUSION: Vitamin E therapy is effective in decreasing the levels of
      EOF in patients on HD and PD, and it is also effective in decreasing lipid
      peroxidation in patients on HD.

PMID- 17173247
TI  - Terminal complement complexes in childhood type I membranoproliferative
      glomerulonephritis.
AB  - BACKGROUND: The role of terminal complement complexes (TCCs), which are the final
      products of complement activation, in the pathogenesis of human
      glomerulonephritis has not been completely elucidated. To clarify the clinical
      significance of TCCs in type I membranoproliferative glomerulonephritis (MPGN),
      we studied TCCs in plasma, renal tissue and urine in pediatric patients with this
      disease. PATIENTS AND METHODS: We measured the concentrations of TCC in plasma
      (n=25) and urine (n=13) using enzyme-linked immunosorbent assay. Frozen tissue
      from 18 renal biopsies were evaluated for the presence of TCC by direct immu
      noperoxidase staining. RESULTS: At the early stage of the disease, TCC
      concentrations in plasma were elevated to above 0.5 arbitrary units (AU)/mL in 14
      of 25 patients (high-TCC group), while the remaining 11 patients showed less than
      0.5 AU/mL (low-TCC group). In the high-TCC group, TCCs were deposited more
      diffusely and intensely in the glomerulus, compared with those in the low-TCC
      group (p=0.034). Furthermore, urinary TCC concentrations in the high-TCC group
      were higher than those in the low-TCC group (p=0.0001). The high-TCC group showed
      not only a poorer response to steroid treatment, but also poorer prognosis than
      the low-TCC group. CONCLUSIONS: These results suggest that, in pediatric patients
      with type I MPGN, TCCs in circulation may play a particular role in TCC formation
      in the glomerulus and in urine. The TCC concentration in plasma could be used as
      a marker of responsiveness to steroid treatment and long-term prognosis.

PMID- 17173248
TI  - Glomerular expression of CTGF, TGF-beta 1 and type IV collagen in diabetic
      nephropathy.
AB  - BACKGROUND: In development of progressive extracellular matrix accumulation,
      connective tissue growth factor (CTGF) may act as a downstream mediator of
      transforming growth factor-beta 1 (TGF-beta 1). However, the association and the
      correlation of these cytokines and extracellular matrix accumulation in human
      diabetic nephropathy (DN) is not fully understood. METHODS: To explore the
      possible involvement of TGF-beta 1 and CTGF in extracellular matrix accumulation
      in DN, high-resolution in situ hybridization with digoxigenin-labeled antisense
      oligonucleotides to CTGF, TGF-beta 1 and type IV collagen mRNAs were performed in
      DN and in histologically normal human kidney (NHK). To quantify expression of
      each mRNA, the fraction of all nuclear cells that were positively stained in the
      cytoplasm was determined in at least 10 randomly selected cross-sections of
      nonsclerotic glomeruli. RESULTS: Both in DN and in NHK, CTGF, TGF-beta 1 and type
      IV collagen mRNAs were mainly expressed by glomerular mesangial, visceral
      epithelial and parietal epithelial cells. The percentages of positive glomerular
      resident cells were significantly higher for each mRNA in DN compared with NHK.
      Especially, the expression of CTGF mRNA was also notably increased in case of DN
      with only mild histopathologic lesions. The extent of expression of each mRNA was
      significantly correlated to that of each other mRNA examined. CONCLUSION: Our
      study indicated that CTGF and TGF-beta may play an important role in glomerular
      histopathologic change in DN.

PMID- 17173249
TI  - Comparison of peritoneal equilibrium test with icodextrin and 2.5% glucose
      dialysis solutions.
AB  - BACKGROUND: Icodextrin provides a different ultrafiltration mechanism than
      glucose-based dialysate. METHODS: To evaluate the difference in the peritoneal
      equilibrium test (PET) with regard to using icodextrin (Ico-PET) and glucose
      dialysate we designed a prospective study using Ico-PET and 2 cross-over
      conventional 2.5% glucose-based dialysate PETs (Gluco 1-PET and Gluco 2-PET)
      administered 3 months before and after the Ico-PET in 58 chronic peritoneal
      dialysis patients. RESULTS: More patients demonstrated higher transport types
      with the Ico-PET than the Gluco 1-PET and Gluco 2-PET (p<0.001). After a dwell
      time of 4 hours, the Ico-PET did not show an ultrafiltration benefit compared
      with the Gluco-PET (272.8 +/- 137.1 mL vs. 348.3 +/- 215.2 mL, p<0.001). The Ico
      PET not only showed significantly higher values in the 0-hour, 2-hour and 4-hour
      dialysate to plasma creatinine concentration ratio (D/P Cr) than those of the
      Gluco 1-PET (p=0.029 and p<0.001, respectively), but also showed higher values in
      the 0-hour and 4-hour D/P Cr than those of the Gluco 2-PET (both p<0.001). The
      total ultrafiltration volume was positively correlated with the 4-hour D/P Cr
      with the Ico-PET (r=0.41, p=0.001), but the correlation was negative with the
      Gluco 1-PET (r=-0.33, p=0.012) and Gluco 2-PET (r=-0.51, p<0.001). The ratio of
      the glucose concentration in the outflow dialysate compared with baseline level
      (D/Do glucose), was also significantly higher with the Ico-PET than with the
      Gluco 1-PET and Gluco 2-PET after both 2 and 4 hours (both p<0.001). CONCLUSIONS:
      The Ico-PET showed a completely different result from the conventional Gluco-PET.
      The Ico-PET provi-des a superior solute transport and inferior ultrafiltration
      rates, and the prevalence of high transporters was also increased with the Ico
      PET.

PMID- 17173250
TI  - Relationship of chronic kidney disease to cardiovascular death and myocardial
      infarction following coronary stenting.
AB  - BACKGROUND: Chronic kidney disease is a risk factor for death in the year
      following myocardial infarction or coronary angioplasty. Whether the risk is
      similar after coronary stenting, whether impaired renal function is associated
      with an increased risk of cardiovascular death or myocardial infarction (MI)
      after coronary stenting and whether this risk is maintained beyond the first year
      are uncertain. METHODS: We analyzed the long-term risks of MI or the combination
      of cardiovascular death and non-fatal MI in patients participating in 4 coronary
      stenting trials with mandated, prospective long-term follow-up. Cox proportional
      hazards models were used to adjust for confounding and to generate multivariable
      odds ratios. RESULTS: Patients (n=1,228) were followed for a median of 5 years.
      There were 125 MIs and 55 cardiovascular deaths. Patients with a serum
      creatinine>or=1.3 mg/dL had markedly elevated risks of cardiovascular death and
      MI that emerged during the first year and were maintained throughout follow-up.
      The adjusted hazard ratio of MI was 2.14 (p=0.006) while the adjusted hazard
      ratio of a combined end point of MI or cardiovascular death was 2.13 (p=0.001).
      The risks were similar in patients with moderate (serum creatinine 1.3-1.9 mg/dL)
      or advanced chronic kidney disease. CONCLUSIONS: The presence of even mild
      chronic kidney disease is associated with a high risk of cardiovascular death and
      MI following coronary stenting. Further research to address the causes of the
      association and to define the best therapy for these patients is necessary.

PMID- 17173252
TI  - Relationship between arterial hypertension and renal damage in chronic kidney
      disease: insights from ABPM.
AB  - BACKGROUND: To date, few studies have used ambulatory pressure monitoring (ABPM)
      in patients with chronic kidney disease (CKD) before the start of dialysis
      treatment. The aim of this study was therefore to ascertain the correlates of
      arterial hypertension assessed by ABPM in CKD patients at their first referral to
      a nephrologist. METHODS: We studied 244 (164 men; mean age 63 years) nondiabetic
      patients with CKD. Each patient had blood pres-sure (BP) measured by 24-hour
      ABPM, creatinine clearance (CrCl) estimated according to the Cockcroft-Gault
      formula, and Hgb concentration, serum lipids, iPTH, daily urinary protein (Uprot)
      and sodium (UNa) excretion assessed using routine methods. RESULTS: According to
      ABPM data analysis, 81 patients were normotensives, 78 were stable hypertensives,
      26 had day-time hypertension and 59 had nocturnal hypertension. ANOVA showed both
      lower CrCl (p=0.0033), and higher Uprot (p<0.0001) in stable and nighttime
      hypertensives as compared with normotensives and daytime hypertensives. In the
      whole group each set of both systolic (SBP) and pulse pressure (PP) readings was
      directly associated with both age and Uprot (p<0.05), and inversely with both
      CrCl and Hgb (p<0.05). In multivariate analysis, however, Uprot emerged among
      modifiable risk factors, as the most significant predictor of both SBP and PP;
      the strength of this association was in the order nighttime PP > nighttime SBP >
      24-hour PP > daytime PP > daytime SBP > 24-hour SBP. CONCLUSION: In CKD patients,
      proteinuria is the strongest correlate of arterial hypertension and particularly
      of increased nocturnal PP, possibly as an expression of vascular damage. On the
      basis of these results, ABPM appears to be the most reliable tool for detecting
      the associations between raised BP (particularly nighttime hypertension) and
      renal damage in CKD patients not yet on renal replacement therapy (RRT).

PMID- 17173251
TI  - Effect of antitubercular medications on blood pressure control in chronic kidney
      disease patients with tuberculosis: a prospective cohort study.
AB  - BACKGROUND: Previous anecdotal reports suggested a decrease in antihypertensive
      medication potency after starting antitubercular medications. This interaction
      could be unpredictable in presence of renal failure due to increased half-lives
      of most commonly used antihypertensive medications. METHODS: In a cohort study
      involving 135 patients with chronic kidney disease (CKD), 62 patients with
      tuberculosis star-ted on antitubercular medications (TB group) were prospectively
      compared with 73 CKD controls (with no TB and not on antitubercular medications)
      for a change in antihypertensive medications. Antihypertensive dose was converted
      to unit score. RESULTS: The TB group had a greater increase in antihypertensive
      medication dose as compared with controls (89% vs. 54%, p<0.0001). In absolute
      terms an overall increase in antihypertensive medications was observed in 60% of
      pa-tients in the TB group, with a 2-fold dose increase from the baseline
      (p<0.0001). Four patients from the TB group de-veloped a hypertensive emergency.
      In multivariate linear regression, the association between TB group and increase
      in antihypertensives remained significant ( beta =0.38; p<0.0001). CONCLUSIONS:
      In CKD patients, antihypertensive medication potency is reduced in TB patients on
      antitubercular the-rapy in a significant number of patients, to a clinically
      significant degree with a potential risk for hypertensive emergency.

PMID- 17173254
TI  - Analysis of safety and efficacy of pegylated-interferon alpha-2a in hepatitis C
      virus positive hemodialysis patients: results from a large, multicenter audit.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection rates are still high in
      hemodialysis (HD) centers in developing countries. Standard interferon (IFN)
      monotherapy is associated with good results in HCV-positive patients (more than
      30% rate of sustained virological response) but with poor tolerance. Pegylated
      interferon (PEG-IFN) is better tolerated and has a more sustained antiviral
      effect in the general population. There have been no large trials to date with
      PEG-IFN in hemodialysis populations. METHODS: We report the largest series to
      date of HCV+ HD patients (n=78) treated with PEG-IFN alfa -2a 135 microg s.c.
      weekly monotherapy. The primary outcomes were (a) efficacy - assessed by the
      viral response at 12, 48 weeks and 6 months after completion of therapy, and (b)
      rate of serious adverse events. RESULTS: In 48/78 (61.5%) patients an early (12
      weeks) viral response was obtained. Viral end-of-treatment response (ETR) was
      evaluated in the 21 patients (26.9%) who reached week 48 on therapy: only 15
      subjects (19.2% of the initial population) had undetectable HCV-RNA levels. In
      these 15 patients, a sustained viral response (SVR) was recorded in 11 - i.e.
      14.1% of the initial intention-to-treat (ITT) population. A high prevalence of
      noncompliance (32%) and of adverse events (83%) was recorded; minor adverse
      effects (flu-like syndrome, mild-to-moderate thrombocytopenia, leukopenia and
      anemia) responded to symptomatic therapy or dose reduction, but often caused lack
      of compliance. The incidence rate of serious adverse events was 0.19/patient-year
      (median time to event 20.5 weeks), and incidence of deaths was 0.11/patient-year.
      CONCLUSIONS: In dialysis patients, PEG-IFN alfa -2a is poorly tolerated and
      associated with a high number of serious adverse events, causing a significant
      lack of compliance/discontinuation of therapy. In this largest HCV-positive
      hemodialysis population survey, we report a low sustained viral response in an
      ITT analysis, compared with previously published historical data using non-PEG
      IFN, a low compliance rate and an unsatisfactory overall safety profile, not
      supporting the superiority of PEG-IFN monotherapy.

PMID- 17173253
TI  - Serial echocardiographic changes in patients on hemodialysis: an evaluation of
      guideline implementation.
AB  - BACKGROUND: Few studies have addressed the description of serial changes in left
      ventricular mass (LVM) and relevant risk factors. All these studies were
      initiated before the implementation of EBPG or K/DOQI guidelines. The aims of our
      study were to prospectively describe trends in left ventricular (LV) structure
      and function, evaluate risk factors for progression of LVM derived from serial
      echocardiographic measurements starting January 2003, 6 months after full
      implementation of EBPG in our unit. METHODS: One hundred seventy-six patients
      were enrolled at baseline, between 1 January 2003 and 1 October 2004; 33 patients
      were excluded from analysis due to poor echocardiographic window, 14 patients
      died and 26 were transplanted or transferred during the follow-up period of
      minimum 12 months. One hundred and three patients were included in the final
      analysis (mean age 51 years, mean follow-up 24.1 +/- 14.4 months).
      Echocardiography was performed at inclusion and at the end of study. Biochemical,
      blood pressure (BP) and medication data were collected and the means of monthly
      values were used. RESULTS: At baseline, 86.4% of the patients had left
      ventricular hypertrophy (LVH) (56.3% concentric hypertrophy, 30.1% eccentric
      hypertrophy, 6.8% concentric remodeling and only 6.8% normal LV geometry), 25.6%
      had systolic dy-sfunction and 50.5% had abnormal LV volume index (LVVI). Similar
      data were recorded at follow-up (82.5%, 44.7%, 37.9%, 7.7%, 9.7%, and 19.5%,
      respectively). Baseline left ventricular mass index (LVMI) significantly
      correlated with hemoglobin (Hb) and total protein level. LVMI at follow-up
      correlated to Hb, SBP, PP, mean level of serum phosphate, calcium x phosphate
      product and cholesterol. Independent predictors for LVMI (multiple regressions)
      were anemia and mineral metabolism markers. In our population, 62.1% of the
      patients had a regression of LVMI, with a mean decrease in LVMI of 12 g/m 2 (1.7
      +/- 11.7 g/m 2 /month) over more than 12 months of guideline implementation.
      Regressors had a significant improvement of anemia, serum phosphate level and
      calcium x phosphate product (p<0.05). CONCLUSION: Our study suggests that a
      holistic interventional approach, targeting various pathogenic mechanisms, as per
      guidelines, can elicit at least a partial regression in LV structural and
      functional abnormalities in hemodialysis patients.

PMID- 17173255
TI  - Predictive value of cytokine gene polymorphisms for the development of end-stage
      renal disease.
AB  - BACKGROUND: Cytokines play a crucial role in different immunopathological
      conditions. Cytokine secretion is reported to be determined by polymorphisms in
      the cytokine genes. Since TNF-alfa and IL-10 are involved in regulation of
      inflammation, and TGF-beta 1 can induce fibrosis and renal insufficiency -
      dominant features of end-stage renal disease (ESRD), we explored the hypothesis
      that polymorphisms of these cytokine genes may be possible genetic susceptibility
      factors for the progression of renal failure. METHODS: We studied the IL-10 (
      1082), TNF-alfa (-308), TGF-beta 1 (codon 10;25) gene single nucleotide
      polymorphisms in 118 healthy donors and 103 patients with ESRD (44 hemodialysis
      patients with diabetic nephropathy and 59 hemodialysis patients with
      glomerulonephritis) using PCR-SSP. RESULTS: Significant associations of ESRD with
      the TGF-beta 1 (codon 10) TT (odds ratio [OR] = 5.31; 95% confidence interval
      [95% CI], 3.77-7.02; p<0.001) and IL-10 (-1082) GG (OR=2.35; 95% CI, 1.67-3.15;
      p<0.01) genotypes were found. Statistical analysis of genotype frequencies made
      separately for the underlying renal disease (diabetes or glomerulo-nephritis)
      revealed the same linkage trend: TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG
      were associated with type 2 diabetic nephropathy (p<0.001 and p<0.05,
      respectively) and chronic glomerulonephritis (p<0.001 and p<0.01, respectively).
      No significant differences in the TNF-alfa , TGF-beta 1 (codon 25) genotype
      distribution between healthy controls and patients with diabetic nephropathy- or
      glomerulonephritis-associated ESRD were detected. CONCLUSIONS: Carriage of the
      TGF-beta 1 (codon 10) TT and IL-10 (-1082) GG genotypes may increase
      susceptibility to ESRD in German patients with type 2 diabetes or
      glomerulonephritis.

PMID- 17173256
TI  - Differences in health-related quality of life between elderly and younger
      patients on hemodialysis.
AB  - BACKGROUND: It has been demonstrated that elderly patients have a great capacity
      of adaptation to renal replacement therapy (RRT). The aim of this study was to
      assess the health-related quality of life (HRQoL) of a cohort of patients at 3
      and 12 months after the start of hemodialysis, searching for differences between
      elderly (aged>or=65 years) and younger (aged <65 years) patients. METHODS: This
      was a longitudinal prospective study of 93 patients starting RRT. HRQoL was
      assessed using the SF-36 health survey and the physical symptom dimension of the
      Kidney Disease Questionnaire (KDQ) at 3 and 12 months from the start of RRT.
      Physical component summary (PCS), mental component summary (MCS) and standardized
      scores, in which a lower score indicated lower HRQoL, by age and sex were
      obtained. RESULTS: Mean (SD) age was 66 years (12.26 years). At 3 months,
      differences between younger patients and elderly ones were statistically
      significant in the general health dimension, and at 12 months in physical
      functioning, role physical, general health dimensions and PCS, indicating less
      loss of HRQoL in elderly patients. At 3 months it was found that the functional
      state measured on the Karnofsky scale was independently associated with PCS
      (p=0.003), and hematocrit to MCS (p=0.036). At 1 year, PCS was independently
      associated with age (p=0.043) and Karnofsky score (p=0.039). CONCLUSIONS: Using
      scores standardized by age and sex, elderly patients had less loss of HRQoL in
      the physical aspects, than younger patients at 1 year from the start of
      hemodialysis.

PMID- 17173257
TI  - Failure of mycophenolate mofetil therapy in primary refractory nephrotic
      syndrome.
AB  - Mycophenolate mofetil (MMF) has been suggested as a promising therapeutic agent
      in the treatment of idiopathic nephrotic syndrome. Two patients with persistent
      nephrotic syndrome, secondary to minimal change disease and idiopathic membranous
      nephropathy, respectively, who were steroid-, cyclophosphamide- and cyclosporine
      resistant, were treated with MMF during a 6-12-month period. In these cases there
      was no beneficial effect from treatment with MMF. Therapy was stopped after 6
      months in case 1 and after 12 months in case 2 due to the persistence of
      proteinuria.

PMID- 17173258
TI  - Asymptomatic right atrial thrombus in a case of nephrotic syndrome.
AB  - Hypercoagulable state in nephrotic syndrome can be complicated by thrombosis in
      unusual sites. We describe the case of a steroid-responsive nephrotic syndrome in
      an adult patient complicated by isolated thrombus in the right atrium which was
      completely asymptomatic. The patient was treated with steroids, anticoagulation
      and excision of the intracardiac thrombus with complete resolution. The case is
      presented in view of its rarity and to highlight the importance of routine
      echocardiography in all cases of nephrotic syndrome.

PMID- 17173259
TI  - Proteinuria in 3 sequential pregnancies following a fourth renal transplant.
AB  - Pregnancy posttransplantation, particularly after kidney transplantation, is
      becoming common. It poses a challenge for transplant physicians, obstetricians
      and neonatologists due to the possible adverse maternal and foetal outcomes. The
      available experience on multiple pregnancies posttransplantation is limited. This
      case study reports 3 successful pregnancies - 5, 13 and 20 years after fourth
      renal transplantation resulting in vaginal deliveries at 37, 34 and 38 weeks - in
      a patient with reflux nephropathy. She developed hypertension, proteinuria and
      abnormal renal function during gestation with each pregnancy, all of which
      reversed after delivery. The reported case demonstrates successful foetal
      outcomes and reversible proteinuria, hypertension and allograft dysfunction
      possibly related to preeclampsia in the mother during her 3 successful
      pregnancies after a fourth renal transplant.

PMID- 17173260
TI  - Membranoproliferative glomerulonephritis in a patient with Wilson's disease.
AB  - Wilson's disease is an autosomal recessive disorder of hepatobiliary copper
      metabolism. Glomerular diseases can ensue during the course of Wilson's disease
      and membranous nephropathy is the eventual pathology in the majority of these
      cases. Membranoproliferative glomerulonephritis (MPGN) has rarely been reported
      in patients with Wilson's disease. Further, in this report, we present a patient
      with Wilson's disease who had developed MPGN during follow-up due to D
      penicillamine therapy. This case is presented to draw attention to the rare
      association of Wilson's disease and MPGN and to discuss the possible underlying
      causes.

PMID- 17173261
TI  - [Cardiac arrhythmias in patients with renal insufficiency treated with periodic
      hemodialysis].
AB  - Despite substantial progress in dialysis technology, cardiovascular disease
      remain the sole major cause of death in chronic dialysis patients. Nearly half of
      deaths on chronic maintenance hemodialysis are secondary to myocardial
      infarction, cardiac arrest, malignant arrhythmias and other cardiac causes. In
      fact, diabetes, anemia, hyperparathyroidism, and hypertension wide prevalence
      among chronic dialysis patients foster structural heart diseases. Moreover fluid
      overload and metabolic abnormalities such as metabolic acidosis, dyskalemia,
      dysmagnesemia lead to an increased risk of clinically significant ventricular
      arrhythmias and sudden cardiac death. During dialysis patients show a non
      homogeneous repolarization through an increase in Q-T duration and Q-T
      dispersion. The dialysis-related sudden variation in extra-cellular potassium,
      calcium and pH levels may be contributing factors to the genesis of an electrical
      disequilibrium in myocardial cells. One of the potential therapeutic options is,
      in fact, adjusting the dialysis bath. The K profiling with non-constant K
      concentration in the dialysate, but with high concentration in the first hour of
      dialysis and progressive reduction until the end of the session, seems very
      promising in reducing the arrhythmic risk in cardiomyopathy patients.

PMID- 17173262
TI  - [Left ventricular hypertrophy in chronic kidney disease].
AB  - Chronic kidney disease (CKD) is associated with increased cardiovascular (CV)
      risk. Left ventricular (LV) hypertrophy (LVH), together with coronary artery
      disease, has been considered the main target of intervention. LVH is highly
      prevalent in CKD even in early stages, as compared to general non-selected
      population. This is mainly due to the multifactorial pathogenesis of LVH in renal
      patients where both haemodynamic and non-haemodynamic stimuli synergically act
      inducing either an increase in left ventricular mass or an LV dilation. Anaemia
      and arterial hypertension seem to be the most important factors. Interventional
      studies have shown that partial correction of anaemia through epoetin, together
      with an arterial hypertension successful therapy through renin-angiotensin system
      acting drugs, such as ACE-inhibitors, were able to induce a LVH regression in
      CKD. Indeed, the unfavourable outcome in patients with both CKD and LVH, whose
      survival is reduced and incidence of fatal and non-fatal CV events increased, can
      be reversed if LVH is regressed by therapy. The most promising strategy in CKD
      seems to be LVH early diagnosis through echocardiography, the correct screening
      of risk factors, a LVM longitudinal monitoring through echo, as well as starting
      treatment in the early stages of CKD, with the aim of improving general and CV
      prognosis for these patients.

PMID- 17173263
TI  - [From CANUSA to ADEMEX: do we need a new paradigm for definition of peritoneal
      dialysis adequacy?].
AB  - Peritoneal dialysis doses were prescribed out of empirical criteria up to the mid
      Ninety Then, the observational CANUSA study and the experimental ADEMEX study
      helped to define adequacy criteria according to urea kinetics model. This review
      analyzes the limits of a definition of adequacy grounded exclusively on urea
      kinetics, as well as the need for new parameters of adequacy. The evidence is
      presented fostering the hypothesis that the control of extra-cellular fluid
      excess and of other cardiovascular risk factors may now be considered a new
      target for adequacy.

PMID- 17173264
TI  - [Polyomavirus BK-associated nephropathy after kidney transplantation].
AB  - Polyomavirus BK (BKV) infection has been lately recognized as a major cause of
      renal allograft dysfunction. BKV-related interstitial nephropathy (PVAN) may
      affect 1-10% of renal allograft recipients, occurring more frequently in the
      first 6 months after transplantation. Progression to irreversible allograft
      failure has been observed in up to 45% of all cases; thanks to increased PVAN
      awareness and improved diagnostic techniques, the rate of graft loss has lowered,
      more consistently in centres with active screening and intervention programs.
      PVAN pathogenesis is characterized by multiple synergizing factors, among which
      immunodepression plays a key role. PVAN diagnosis requires the evaluation of a
      renal biopsy showing polyomavirus cytopathic changes and confirming BKV through
      an ancillary technique such as immunohistochemistry. Given the focal nature of
      the disease, early diagnosis may be difficult to obtain. Thus, quantification of
      BKV-DNA in plasma has been suggested as surrogate marker for PVAN. To date, given
      the lack of controlled trials, there is no consensus on a 'standard' management
      of PVAN. However, evidence based on reported observations suggests that a step
      wise reduction of immunosuppression, preceded by pulsed steroids in case of
      coexistent acute rejection, may improve outcomes. Additional options may be
      represented by drugs with antiviral activity, such as cidofovir, leflunomide or
      quinolones. Application of a preventive treatment based on viremia monitoring has
      been recently proposed.

PMID- 17173265
TI  - [Natural history of HCV infection and risk of death in a cohort of patients on
      long-term hemodialysis].
AB  - BACKGROUND: HCV infection represents the major cause of chronic liver disease in
      hemodialysis and renal transplant patients. The clinical course of liver disease
      in hemodialysis patients is generally asymptomatic. Only few studies describe the
      natural history of HCV infection in haemodialysis patients, showing an
      association between HCV infections and poor survival. METHODS: A prospective
      cohort study of our haemodialysis population was conducted to define the natural
      history of HCV infection and its relation to mortality. 77 patients on
      haemodialysis were enrolled, 24 (31%) of whom were anti-HCV and 53 (69%) anti-HCV
      negative. RESULTS: The HCV-RNA was positive in 18 of the 24 anti-HCV-positive
      subjects (75%). None of the anti-HCV-negative subjects was HCV-RNA-positive.
      Eight of the 18 HCV-RNA-positive patients (40%) developed cirrhosis with portal
      hypertension and ascites within 7 years after the first increase of GPT. Seven of
      these died, nobody developed hepatocarcinoma (HCC). During 58+/-37-follow-up
      months mortality rate was higher among anti-HCV-positive patients than among anti
      HCV-negative. Besides, the 6 deaths occurred only among anti-HCV-positive and HCV
      RNA-positive patients. CONCLUSION: in our haemodialysis patient population the
      presence of antibodies anti-HCV and HCV-RNA is associated with an increased risk
      of developing liver cirrhosis and of death, in comparison to anti-HCV-negative
      patients. Our data show that anti-HCV-positive patients have an accelerated
      course towards chronic hepatopathy and cirrhosis.

PMID- 17173266
TI  - [A contrast with good intentions].
AB  - A seventy-five-year-old woman with moderate chronic renal failure was admitted to
      evaluate a complex renal cyst in the frame of acquired cystic kidney disease.
      Computed tomography (CT) was performed without contrast media due to the risk of
      radiocontrast-induced nephrotoxicity. Sonographic investigation at our ultrasound
      unit revealed a hypoechoic lesion measuring 20x20 mm in size by conventional B
      mode sonography, confirmed by NTHI. The Hypoechoic lesion was consistent with
      complex renal cyst or renal tumour. This finding triggered investigation with
      CEUS.A sulphur hexafluoride-filled microbubble contrast medium was injected
      intravenously. The focal lesion CES pattern was characterized by intralesional
      enhancement in the arterial phase. Further diagnostic imaging including CT with
      contrast media confirmed a lesion consistent with renal tumour. The patient
      underwent right-sided nephrectomy; histopathological work-up revealed a renal
      cell carcinoma. Contrast-enhanced sonography could be clinically useful for the
      differential diagnosis of kidney lesions in patients with chronic renal failure.

PMID- 17173267
TI  - The role of internal water molecules in the structure and function of the
      rhodopsin family of G protein-coupled receptors.

PMID- 17173269
TI  - Functional cell-surface display of a lipase-specific chaperone.
AB  - Lipases are important enzymes in biotechnology. Extracellular bacterial lipases
      from Pseudomonads and related species require the assistance of specific
      chaperones, designated "Lif" proteins (lipase specific foldases). Lifs, a unique
      family of steric chaperones, are anchored to the periplasmic side of the inner
      membrane where they convert lipases into their active conformation. We have
      previously shown that the autotransporter protein EstA from P. aeruginosa can be
      used to direct a variety of proteins to the cell surface of Escherichia coli.
      Here we demonstrate for the first time the functional cell-surface display of the
      Lif chaperone and FACS (fluorescence-activated cell sorting)-based analysis of
      bacterial cells that carried foldase-lipase complexes. The model Lif protein,
      LipH from P. aeruginosa, was displayed at the surface of E. coli cells. Surface
      exposed LipH was functional and efficiently refolded chemically denatured lipase.
      The foldase autodisplay system reported here can be used for a variety of
      applications including the ultrahigh-throughput screening of large libraries of
      foldase variants generated by directed evolution.

PMID- 17173270
TI  - A resonance energy transfer immunoassay based on a thiol-reactive ruthenium donor
      dye and a longwave-emitting acceptor.
AB  - A novel immunoassay is described that applies a thiol-reactive ruthenium metal
      ligand complex as the donor dye in a luminescence energy transfer (LET) detection
      scheme. Unlike amine-reactive labels, the LET with a thiol label allows improved
      specificity and better reproducibility of labelling positions on proteins,
      because the number of reactive thiol groups of proteins is distinctly smaller.
      This helps to reduce the risk of over-labelling and self-quenching of the
      fluorophore. The synthesis of the thiol label was significantly improved,
      resulting in almost quantitative yields of pure product. The absorption and
      emission maxima of the ruthenium donor dye are at 460 nm and 600 nm,
      respectively, and a Stokes' shift of 140 nm warrants distinct separation of
      excitation and emission wavelengths even in turbid samples. A cyanine dye with an
      absorption maximum at 642 nm was chosen as the acceptor label because it has good
      overlap with the emission spectrum of the donor label. The emission of the
      acceptor peaks at 660 nm, thus further increasing the Stokes' shift (to an
      overall 200 nm). The quantification of anti-HSA with the LET immunoassay is
      possible with this new approach at concentrations as low as 220 pmol L(-1).

PMID- 17173271
TI  - Chemical biology: Directing biosynthesis.

PMID- 17173274
TI  - PFO closure for prevention of recurrent stroke in patients after cryptogenic
      stroke: the imperative of completing randomized controlled trials.

PMID- 17173275
TI  - Catheter-based atrial shunt occlusion, when the going gets even tougher:
      editorial comment to use of a straight, side-hole (SSH), delivery sheath for
      improved delivery of Amplatzer ASD occluder.

PMID- 17173276
TI  - On horse sense and horse feathers: an argument against insistence on enrolling
      cryptogenic stroke patients with patent foramen ovale in randomized clinical
      trials.

PMID- 17173277
TI  - Cryptogenic stroke patients with patent foramen ovale should be closed only in
      the setting of a randomized control trial.

PMID- 17173278
TI  - Effect of omeprazole on the pharmacokinetics of paricalcitol in healthy subjects.
AB  - Paricalcitol capsules are indicated for the prevention and treatment of secondary
      hyperparathyroidism in chronic kidney disease (CKD). Proton pump inhibitors are
      prescribed to CKD patients to treat gastroesophageal reflux. This was a single
      dose, crossover study evaluating the effect of omeprazole, change in gastric pH
      as a result thereof, on the pharmacokinetics (PK) of paricalcitol. Twenty-six
      healthy subjects were administered paricalcitol capsules (16 microg) alone
      (regimen A), and following a single dose of OMP (40 mg) (regimen B), with a
      washout of at least 7 days. Plasma samples for paricalcitol concentrations were
      collected for 48 h post-paricalcitol dose. The plasma paricalcitol concentrations
      were measured using an LC-MS/MS assay (LOQ=0.02 ng/ml) and paricalcitol
      pharmacokinetic parameters were estimated using non-compartmental methods. The
      point estimates and the corresponding 90% confidence intervals for Cmax and AUC0
      infinity to evaluate paricalcitol-omeprazole interaction were 1.032 [0.920-1.158]
      and 1.041 [0.951-1.139], respectively. No significant differences in Tmax
      (regimen A: 2.9 h vs regimen B: 2.6 h) or t1/2 (6.83 h vs 6.6 h) between the
      regimens were observed. Hence, the co-administration of omeprazole does not
      affect the PK of paricalcitol. Both regimens were well tolerated and no apparent
      differences among the regimens with respect to safety were observed.

PMID- 17173279
TI  - A comparison of African American and Latina social networks as indicators for
      culturally tailoring a breast and cervical cancer education intervention.
AB  - As similar cancer health disparities have been documented for African American
      (AA) women and Latinas, it would be important to determine whether comparable
      interventions could be used to increase screening among these 2 culturally
      different populations. This paper reports research findings comparing cultural
      dimensions of breast and cervical cancer as they impact Latino and AA social
      networks and explore the feasibility of creating outreach models that may serve
      both groups. An existing intervention that integrates the social roles and
      relationships of AA women, The Witness Project(R), is used as a framework for
      tailoring an intervention for Latino communities. Findings and data from focus
      groups and key informant interviews were collected from more than 120 Latinos in
      Arkansas and New York City. These findings are analyzed using the Pen-3 Model,
      categorized, and compared with previous social role and network information from
      AA women as reflected in the Witness Project(R) intervention model. The findings
      from this study demonstrated variations between AA women and Latinas with regard
      to roles and gender relationships while demonstrating similarities with regard to
      spiritual beliefs and attitudes toward cancer. We applied our results to
      culturally tailor and develop a breast and cervical cancer intervention,
      Esperanza y Vidatrade mark (Hope and Life), that incorporates Latino values and
      social relationships. This study demonstrates that a proven education and
      outreach model for AA women may provide a framework for creating a culturally
      appropriate intervention for Latinas. Further research is needed to study the
      efficacy of the new model. Cancer 2007. (c) 2006 American Cancer Society.

PMID- 17173280
TI  - Facilitating research participation and improving quality of life for African
      American prostate cancer survivors and their intimate partners. A pilot study of
      telephone-based coping skills training.
AB  - African American men experience worse prostate cancer outcomes compared with
      those of Caucasian men, not only in incidence and mortality rates, but also in
      coping with the side effects of treatment. Unfortunately, African American men
      have been significantly under-represented in research evaluating the efficacy of
      psychosocial interventions for improving coping in prostate cancer survivors.
      This pilot study explored the feasibility and efficacy of coping skills training
      (CST), an intervention developed to enhance coping with treatment side effects in
      a sample of African American prostate cancer survivors and their intimate
      partners. The intervention was delivered in a telephone-based format designed to
      facilitate research participation. A total of 40 couples were randomized to
      either 6 sessions of CST or usual care. Survivors completed measures of disease
      specific quality of life (QOL) related to urinary, sexual, bowel, and hormonal
      symptom domains, as well as measures of global QOL (i.e., physical functioning
      and mental health). Partners completed measures of caregiver strain, mood, and
      vigor. Analysis of data from 30 couples (12 couples in CST, 18 couples in usual
      care) indicated that CST produced moderate to large treatment effects for QOL
      related to bowel, urinary, sexual, and hormonal symptoms. Partners who underwent
      CST reported less caregiver strain, depression, and fatigue, and more vigor, with
      moderate effect sizes observed that approached conventional levels of statistical
      significance. These preliminary findings suggest that telephone-based CST is a
      feasible approach that can successfully enhance coping inAfrican American
      prostate cancer survivors and their intimate partners. Cancer 2007. (c) 2006
      American Cancer Society.

PMID- 17173281
TI  - Interaction of malaria parasite-inhibitory antibodies with the merozoite surface
      protein MSP1(19) by computational docking.
AB  - Merozoite surface protein 1 (MSP1) of the malaria parasite Plasmodium falciparum
      is an important vaccine candidate antigen. Antibodies specific for the C-terminal
      maturation product, MSP1(19), have been shown to inhibit erythrocyte invasion and
      parasite growth. Specific monoclonal antibodies react with conformational
      epitopes contained within the two EGF-like domains that constitute the antigen
      MSP1(19). To gain greater insight into the inhibitory process, the authors
      selected two strongly inhibitory antibodies (designated 12.8 and 12.10) and
      modeled their structures by homology. Computational docking was used to generate
      antigen-antibody complexes and a selection filter based on NMR data was applied
      to obtain plausible models. Molecular Dynamics simulations of the selected
      complexes were performed to evaluate the role of specific side chains in the
      binding. Favorable complexes were obtained that complement the NMR data in
      defining specific binding sites. These models can provide valuable guidelines for
      future experimental work that is devoted to the understanding of the action
      mechanism of invasion-inhibitory antibodies.

PMID- 17173282
TI  - Structure and properties of a truely apo form of AraC dimerization domain.
AB  - The arabinose-binding pockets of wild type AraC dimerization domains crystallized
      in the absence of arabinose are occupied with the side chains of Y31 from
      neighboring domains. This interaction leads to aggregation at high solution
      concentrations and prevents determination of the structure of truely apo AraC. In
      this work we found that the aggregation does not significantly occur at
      physiological concentrations of AraC. We also found that the Y31V mutation
      eliminates the self-association, but does not affect regulation properties of the
      protein. At the same time, the mutation allows crystallization of the
      dimerization domain of the protein with only solvent in the arabinose-binding
      pocket. Using a distance difference method suitable for detecting and displaying
      even minor structural variation among large groups of similar structures, we find
      that there is no significant structural change in the core of monomers of the
      AraC dimerization domain resulting from arabinose, fucose, or tyrosine occupancy
      of the ligand-binding pocket. A slight change is observed in the relative
      orientation of monomers in the dimeric form of the domain upon the binding of
      arabinose but its significance cannot yet be assessed.

PMID- 17173283
TI  - Comparative in vitro degradation of the human hemorphin LVV-H7 in mammalian
      plasma analysed by capillary zone electrophoresis and mass spectrometry.
AB  - The human hemorphin LVV-H7 (L32VVYPWTQRF41) is a hemoglobin-beta, -gamma, -delta
      or -epsilon chain derived cationic decapeptide of the micro-opioid receptor
      binding family. It exhibits potential pharmacological value relevant, for
      example, for blood pressure regulation, learning performance and Alzheimer's
      disease. The regulatory potency is strictly dependent on the length of the amino
      acid sequence which is sensitive towards proteinases from tissues and plasma. To
      analyse LVV-H7 in vitro degradation in mammalian plasma, a novel multi-component
      quantitative capillary zone electrophoretic (CZE) procedure was applied, combined
      with qualitative metabolite profiling by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In all
      types of plasma, LVV-H7 was N-terminally truncated generating four metabolites
      (M1-M4) with an intact C-terminus: M1 (V33VYPWTQRF41), M2 (V34YPWTQRF41), M3
      (Y35PWTQRF41) and M4 (W37TQRF41). In EDTA plasma these degradation products were
      detected exclusively, whereas in citrate and heparin plasma four further
      metabolites appeared resulting from additional C-terminal cleavage of the
      dipeptide R40F41: M5 (L32VVYPWTQ39), M6 (V33VYPWTQ39), M7 (V34YPWTQ39) and M8
      (Y35PWTQ39). In the presence of selective proteinase inhibitors aminopeptidase M
      and angiotensin-converting enzyme (for N- and C-terminal truncation,
      respectively) were identified as plasma enzymes responsible for hemorphin
      degradation. Furthermore, striking inter-mammalian species distinctions were
      detected revealing strongly differing degradation velocities but similar
      metabolite patterns.

PMID- 17173284
TI  - Computational proteomics of biomolecular interactions in the sequence and
      structure space of the tyrosine kinome: deciphering the molecular basis of the
      kinase inhibitors selectivity.
AB  - Understanding and predicting the molecular basis of protein kinases specificity
      against existing therapeutic agents remains highly challenging and deciphering
      this complexity presents an important problem in discovery and development of
      effective cancer drugs. We explore a recently introduced computational approach
      for in silico profiling of the tyrosine kinases binding specificity with a class
      of the pyrido-[2,3-d]pyrimidine kinase inhibitors. Computational proteomics
      analysis of the ligand-protein interactions using parallel simulated tempering
      with an ensemble of the tyrosine kinases crystal structures reveals an important
      molecular determinant of the kinase specificity. The pyrido-[2,3-d]pyrimidine
      inhibitors are capable of dynamically interacting with both active and inactive
      forms of the tyrosine kinases, accommodating structurally different kinase
      conformations with a similar binding affinity. Conformational tolerance of the
      protein tyrosine kinases binding with the pyrido[2,3-d]pyrimidine inhibitors
      provides the molecular basis for the broad spectrum of potent activities and
      agrees with the experimental inhibition profiles. The analysis of the pyrido[2,3
      d]pyrimidine sensitivities against a number of clinically relevant ABL kinase
      mutants suggests an important role of conformational adaptability of
      multitargeted kinase inhibitors in developing drug resistance mechanisms. The
      presented computational approach may be useful in complementing proteomics
      technologies to characterize activity signatures of small molecules against a
      large number of potential kinase targets.

PMID- 17173285
TI  - Cooperative folding mechanism of a beta-hairpin peptide studied by a
      multicanonical replica-exchange molecular dynamics simulation.
AB  - G-peptide is a 16-residue peptide of the C-terminal end of streptococcal protein
      G B1 domain, which is known to fold into a specific beta-hairpin within 6 micros.
      Here, we study molecular mechanism on the stability and folding of G-peptide by
      performing a multicanonical replica-exchange (MUCAREM) molecular dynamics
      simulation with explicit solvent. Unlike the preceding simulations of the same
      peptide, the simulation was started from an unfolded conformation without any
      experimental information on the native conformation. In the 278-ns trajectory, we
      observed three independent folding events. Thus MUCAREM can be estimated to
      accelerate the folding reaction more than 60 times than the conventional
      molecular dynamics simulations. The free-energy landscape of the peptide at room
      temperature shows that there are three essential subevents in the folding pathway
      to construct the native-like beta-hairpin conformation: (i) a hydrophobic
      collapse of the peptide occurs with the side-chain contacts between Tyr45 and
      Phe52, (ii) then, the native-like turn is formed accompanying with the hydrogen
      bonded network around the turn region, and (iii) finally, the rest of the
      backbone hydrogen bonds are formed. A number of stable native hydrogen bonds are
      formed cooperatively during the second stage, suggesting the importance of the
      formation of the specific turn structure. This is also supported by the
      accumulation of the nonnative conformations only with the hydrophobic cluster
      around Tyr45 and Phe52. These simulation results are consistent with high phi
      values of the turn region observed by experiment.

PMID- 17173286
TI  - Temperature dependence of the NMR generalized order parameter.
AB  - The study of protein conformational dynamics is motivated in large part by a
      desire to understand the forces present at different sites throughout the
      molecular structure. The generalized order parameter determined by NMR
      spectroscopy has played a central role in the study of protein dynamics on the
      picosecond-nanosecond time scale. A modeling procedure is presented for analysis
      of the temperature dependence of the generalized order parameter that extends a
      previous analysis (Massi and Palmer, J Am Chem Soc 2003;125:11158-11159). As part
      of this procedure, the potential of mean force is characterized for the N-H bond
      vectors of the protein backbone. This procedure accounts for the observed
      temperature dependence of the generalized order parameter in a representative
      data set from the B1 domain of Streptococcal protein G (Seewald, Pichumani,
      Stowell, Tibbals, Regan, and Stone, Protein Sci 2000;9:1177-1193). The results
      indicate a general trend, in which the force constants associated with the
      potential of mean force decrease with increasing temperature. The analysis also
      provides evidence for variations in the potential of mean force for different
      secondary structural elements.

PMID- 17173287
TI  - Enzyme-substrate interactions revealed by the crystal structures of the archaeal
      Sulfolobus PTP-fold phosphatase and its phosphopeptide complexes.
AB  - The P-loop-containing protein phos-phatases are important regulators in signal
      transduction. These enzymes have structural and functional similarity with a
      conserved sequence of Dx(25-41)HCxxGxxR(T/S) essential for catalysis. The
      singular protein tyrosine phosphatase (PTP) from archaeal Sulfolobus solfataricus
      is one of the smallest known PTPs with extreme thermostability. Here, we report
      the crystal structure of this phosphatase and its complexes with two tyrosyl
      phosphopeptides A-(p)Y-R and N-K-(p)Y-G-N. The structure suggests the minimal
      structural motif of the PTP family, having two variable sequences inserted
      between the beta2-beta3 and beta3-beta4 strands, respectively. The phosphate of
      both phosphopeptide substrates is bound to the P-loop through several hydrogen
      bonds. Comparison of several phosphatase-substrate complexes revealed that Gln135
      on the Q-loop has different modes of recognition toward phosphopeptides. The
      substrate specificity of SsoPTP is primarily localized at the phosphotyrosine,
      suggesting that this phosphatase may be a prototypical PTP.

PMID- 17173288
TI  - Steiner minimal trees, twist angles, and the protein folding problem.
AB  - The Steiner Minimal Tree (SMT) problem determines the minimal length network for
      connecting a given set of vertices in three-dimensional space. SMTs have been
      shown to be useful in the geometric modeling and characterization of proteins.
      Even though the SMT problem is an NP-Hard Optimization problem, one can define
      planes within the amino acids that have a surprising regularity property for the
      twist angles of the planes. This angular property is quantified for all amino
      acids through the Steiner tree topology structure. The twist angle properties and
      other associated geometric properties unique for the remaining amino acids are
      documented in this paper. We also examine the relationship between the Steiner
      ratio rho and the torsion energy in amino acids with respect to the side chain
      torsion angle chi(1). The rho value is shown to be inversely proportional to the
      torsion energy. Hence, it should be a useful approximation to the potential
      energy function. Finally, the Steiner ratio is used to evaluate folded and
      misfolded protein structures. We examine all the native proteins and their decoys
      at http://dd.stanford.edu. and compare their Steiner ratio values. Because these
      decoy structures have been delicately misfolded, they look even more favorable
      than the native proteins from the potential energy viewpoint. However, the rho
      value of a decoy folded protein is shown to be much closer to the average value
      of an empirical Steiner ratio for each residue involved than that of the
      corresponding native one, so that we recognize the native folded structure more
      easily. The inverse relationship between the Steiner ratio and the energy level
      in the protein is shown to be a significant measure to distinguish native and
      decoy structures. These properties should be ultimately useful in the ab initio
      protein folding prediction.

PMID- 17173289
TI  - Well-differentiated fetal adenocarcinoma of the lung: cytomorphologic features on
      fine-needle aspiration with emphasis on use of beta-catenin as a useful
      diagnostic marker.
AB  - Well-differentiated fetal adenocarcinoma (WDFA), also known as low grade
      adenocarcinoma of the fetal lung type, is a rare pulmonary neoplasm now
      considered to be a variant of lung adenocarcinoma rather than a type of pulmonary
      blastoma. Upregulation of the Wnt signaling pathway with subsequent aberrant
      nuclear/cytoplasmic beta-catenin expression has been recently described in these
      tumors providing a possible pathogenetic role for this gene in WDFA. We describe
      the cytomorphologic findings of a case of WDFA in a 36-yr-old female patient and
      emphasize the diagnostic utility of aberrant nuclear/cytoplasmic expression of
      beta-catenin as an adjunct to the correct preoperative recognition of this tumor
      on aspiration cytology.

PMID- 17173290
TI  - Comparative analysis of various cytohistological techniques in diagnosis of lung
      diseases.
AB  - A prospective study was conducted on 100 patients divided in two groups who
      underwent fiberoptic bronchoscopy (FOB). Group I consisted of 60 cases of
      suspected lung malignancy on clinical and radiological examination, while group
      II consisted of 40 cases of nonneoplastic lung diseases. Pre-FOB sputum,
      bronchoalveolar lavage (BAL), and bronchial brushing (BB) were done in all the
      cases, while forceps biopsy (FB), transbronchial needle aspiration (TBNA), and
      transthoracic needle aspiration were done in 56, 25, and 15 patients,
      respectively. BB and FB showed a sensitivity of 70.83 and 70% respectively in the
      diagnosis of malignancy. BAL was found to be positive in 37.5% patients. TBNA had
      the highest sensitivity of 83.33% whereas pre-FOB sputum and post-FOB sputum were
      positive only in 27.58 and 29.06% cases. In nonneoplastic group, BAL showed
      sensitivity of 80 and 83.33% in diagnosing tuberculosis and fungal diseases
      whereas BB was positive in 60 and 66.66% patients, respectively. Thus a
      combination of various cytohistological techniques results in a statistically
      significant increase in the diagnostic yield of various neoplastic and
      nonneoplastic lung diseases. BB, FB, and TBNA are complimentary in diagnosis of
      various lung malignancies whereas BAL is a useful procedure in detection of
      infectious diseases.

PMID- 17173291
TI  - Utility of millipore filter and cell block in thyroid needle aspirates: which
      method is superior?
AB  - The main goal of thyroid fine-needle aspiration (FNA) is to distinguish nodules
      that require surgery from those that do not, thereby decreasing the number of
      diagnostic thyroidectomies. Several cytologic preparations are used to reach a
      definitive diagnosis, including smears using conventional stains, such as Diff
      Quik (DQ) and Papanicolaou (Pap), millipore filters (MF), and cell blocks (CB).
      This study is undertaken to study the efficacy and adequacy to reach a definitive
      diagnosis of two cytologic preparations, MF and CB, in thyroid aspirates. All
      thyroid needle aspirates performed at Emory University Hospitals from January
      2003 to April 2005 that had both MF and CB preparations for microscopic
      evaluation were studied. Conventional stains (DQ and Pap) were prepared. An
      initial aliquot of the specimen was divided for MF, and the remaining specimen
      submitted for CB preparation. All MF and CB slides were reviewed blindly.
      Adequacy criteria were assessed as 6-8 groups of follicular cells, with each
      containing 10 or more cells. Patient demographics, cytologic diagnoses, and
      follow-up information were retrieved. A total of 218 cases met our criteria; 21
      of these cases were excluded due to lack of available diagnostic slides. Thus, a
      total of 197 cases were studied. Approximately two-third of the cases (57.9%)
      were diagnosed on DQ- and Pap-stained smears only, in which both CB and MF were
      inadequate. About 4.6% of the cases were diagnostic on both CB and MF; 36.0% on
      MF only, and 1.5% on CB preparation only. In more than half the cases (57.9%),
      diagnosis of thyroid FNA was rendered only on conventional stained smears. MF
      smears appeared to be superior for diagnostic yield (40.6%) than CB (6.1%), which
      is dependent on specimen cellularity. Therefore, MF rather than CB should be
      added to conventional stained smears (DQ and Pap) to supplement the diagnostic
      yield, especially in specimens of low cellularity.

PMID- 17173292
TI  - Diagnosis of foregut and tailgut cysts by endosonographically guided fine-needle
      aspiration.
AB  - Foregut, hindgut, and tailgut cysts are uncommon developmental anomalies.
      Clinical and radiological diagnosis can present many challenges, especially in
      adult patients or when the lesions are in unique locations. Thus, diagnosis has
      traditionally been provided upon surgical resection. We describe the diagnoses of
      a gastric foregut cyst and a retrorectal tailgut cyst by endosonographically
      guided fine-needle aspiration in two adults. The common cytologic features of the
      specimens are ciliated epithelial cells, proteinaceous material with degenerated
      debris, histiocytes, and benign appearing epithelium of squamous and/or
      gastrointestinal type that lack cytologic atypia. The identification of ciliated
      columnar cells is the key finding. Cytologic diagnosis via endosonographically
      guided fine-needle aspiration of foregut/hindgut cyst is accurate and less
      traumatic than surgical biopsies.

PMID- 17173293
TI  - Whole, Turret and step methods of rapid rescreening: is there any difference in
      performance?
AB  - We compared the performance of the Whole, Turret and Step techniques of 100%
      rapid rescreening (RR) in detection of false-negatives in cervical cytology. We
      tested RR performance with cytologists trained and among those without training.
      We revised 1,000 consecutive slides from women participating in an ongoing
      international screening trial. Two teams of experienced cytologists performed the
      RR techniques: one trained in RR procedures and the other not trained. The
      sensitivities in the trained group were Whole 46.6%, Turret 47.4% and Step 50.9%;
      and in the non-trained group were 38.6, 31.6 and 47.4%, respectively. The kappa
      coefficient showed a weak agreement between the two groups of cytologists and
      between the three RR techniques. The RR techniques are more valuable if used by
      trained cytologists. In the trained group, we did not observe significant
      differences between the RR techniques used, whereas in the non-trained group, the
      Step technique had the best sensitivity.

PMID- 17173294
TI  - Review of Penner's criteria for proficiency testing in cytopathology:
      implications for the redesign of the federally mandated proficiency testing in
      cytopathology.
AB  - Thirty-three years ago Penner advocated six criteria for the performance of
      proficiency testing in cytopathology (PTC). Since that time, several further
      requirements have been added by other authors. The present article critically
      evaluates and modifies the original criteria and adds two more principles,
      validity and reliability, that we recognize as crucially important in the
      performance of PTC. The revised criteria should be taken into consideration in
      the planned technical redesign of the nationwide PTC.

PMID- 17173295
TI  - Invasive micropapillary carcinoma of the breast: Cytomorphology of a metastatic
      deposit.

PMID- 17173296
TI  - Unraveling the mystique case of pseudotumor syndrome of pelvis.

PMID- 17173297
TI  - Atypical squamous cells, cannot exclude high grade intraepithelial lesion (ASC
      H): does HPV matter?
AB  - The role of human papillomavirus (HPV) in cases diagnosed as atypical squamous
      cells, cannot exclude high squamous grade intraepithelial lesion (ASC-H) in
      cervical specimens is not well established. The objective of this study is to
      evaluate the role of HPV status in cases of ASC-H in a major cancer center. One
      hundred thirty-two patients with a diagnosis of ASC-H were identified over a 4-yr
      period in our institution. Forty-four of 132 cases were evaluated for high-risk
      HPV and had biopsy follow-up. The positive predictive value (PPV) of ASC-H for
      high-grade squamous intraepithelial lesions overall was 32% while PPV of ASC-H
      with associated HR HPV was 42%. This increase was statistically significant with
      P = 0.003 and suggest that HPV testing might be useful to increase the PPV of ASC
      H.

PMID- 17173299
TI  - Weeding atypical glandular cell look-alikes from the true atypical lesions in
      liquid-based Pap tests: a review.
AB  - The purpose of this review is to identify features that separate atypical
      glandular cells (AGC) associated with glandular neoplasia from its mimickers,
      both benign and neoplastic. We reviewed cases of AGC diagnosed on liquid-based
      Pap tests (LBP) for which corresponding histological follow-up was available. A
      review of the literature for similar studies in LBP tests was also conducted. We
      find that certain benign mimics can be reliably separated from AGC, but recommend
      caution in attempting to increase specificity at the risk of losing sensitivity.
      Although accounting for only a small percentage of diagnoses AGC require a
      thorough clinical evaluation, including colposcopy. Most cases are ultimately
      found to be benign. When evaluating smears suspicious for AGC, it is important to
      examine the subtle features which make truly atypical cells discernible from
      their numerous benign mimickers.

PMID- 17173298
TI  - Diagnostic effects of prolonged storage on fresh effusion samples.
AB  - The effects on morphology and diagnostic interpretation of delayed processing of
      refrigerated effusion samples have not been well documented. The potential for
      cellular degeneration has led many laboratories to reflexively fix samples rather
      than submit fresh/refrigerated samples for cytologic examination. We sought to
      determine if effusion specimens are suitable for morphologic, immunocytochemical,
      and DNA-based molecular studies after prolonged periods of refrigerated storage
      time. Ten fresh effusion specimens were refrigerated at 4 degrees C; aliquots
      were processed at specific points in time (days 0, 3, 5, 7, 10, 14). Specimens
      evaluated included four pleural (3 benign, 1 breast adenocarcinoma) and six
      peritoneal (2 ovarian adenocarcinomas, 1 malignant melanoma, 2 mesotheliomas, 1
      atypical mesothelial) effusions. The morphology of the cytologic preparations
      from the 10 effusions was preserved and interpretable after 14 days of storage at
      4 degrees C. The immunocytochemical profile of the samples (AE1/AE3, EMA,
      calretinin, and LCA) was consistent from day 0 to day 14. Amplifiable DNA was
      present in all samples tested on day 14. We conclude that cytopathologic
      interpretation of effusion samples remains reliable with refrigeration at 4
      degrees C even if processing is delayed.

PMID- 17173301
TI  - Parotid gland fine-needle aspiration cytology: an approach to differential
      diagnosis.
AB  - Parotid glands can undergo a wide range of pathologic changes that may be
      difficult to characterize by clinical features alone. No single diagnostic
      modality is currently accepted unequivocally as the definitive approach to
      parotid gland enlargement or tumors. Although it is generally accepted that fine
      needle aspiration (FNA) biopsy is useful in the preoperative setting, the
      accuracy is highly dependent on both operator experience and the interpretative
      skills of the cytopathologist. Results of FNA biopsy must be considered in a
      global context, in conjunction with clinical and radiographic findings. The
      objectives of this paper are threefold: (1) to define the clinical role of
      parotid FNA, such that pathologists performing and/or interpreting such specimens
      have a clearer understanding of the expectations of our surgical colleagues; (2)
      to clearly describe a protocol for the performance of parotid FNA biopsy,
      including a discussion of complications and pitfalls; and (3) to present the
      cytologic differential diagnoses of diverse clinicopathologic parotid gland
      processes that may present as generalized enlargement, cystic lesions, or
      discrete masses.

PMID- 17173300
TI  - The role of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle
      aspiration in distinguishing pancreatic cystic lesions.
AB  - Distinguishing mucinous from nonmucinous cystic lesions of the pancreas often
      constitutes a diagnostic dilemma. The clinical management differs between such
      lesions; therefore it is important to make an accurate preoperative diagnosis.
      Various centers have reported conflicting results regarding their ability to
      detect mucin-producing neoplastic cells and appropriately reach a diagnosis based
      on endoscopic ultrasound (EUS) guided FNA. The aim of this study is to assess the
      ability of EUS-FNA cytology to diagnose and differentiate mucinous from
      nonmucinous pancreatic cystic lesions. We reviewed records of patients who
      underwent EUS of pancreatic cystic lesions. If FNA was performed and mucinous
      neoplasm was suspected, aspirate was evaluated for cytomorphology and presence of
      mucin. FNA results were compared to final histologic diagnosis if surgery was
      performed. Cytologic diagnosis was provided for 28/30 (93%). By comparing EUS-FNA
      diagnoses with final surgical pathology, FNA accurately diagnosed in 10/11 cases
      with sensitivity and specificity for detection of malignancy of 100 and 89,
      respectively, while the accuracy for identification of mucinous cystic neoplasms
      was 100%. Our results indicate that in the appropriate clinical and imaging
      setting, EUS-FNA cytology with analysis for mucin production by tumor cells is an
      important test in distinguishing pancreatic cystic lesions and guiding further
      management.

PMID- 17173302
TI  - Small cell desmoplastic tumour: morphological findings from an abdominal lesion
      studied with fine-needle aspiration.

PMID- 17173303
TI  - Correlations between dynamic contrast-enhanced magnetic resonance imaging-derived
      measures of tumor microvasculature and interstitial fluid pressure in patients
      with cervical cancer.
AB  - PURPOSE: To correlate permeability (rk(trans)), extracellular volume fraction
      (rv(e)), relative to muscle and initial area under the enhancement curve
      (IAUC(60m)) determined by dynamic contrast-enhanced magnetic resonance imaging
      (DCE-MRI) with in vivo measurements of interstitial fluid pressure (IFP) in
      patients with cervical cancer. MATERIALS AND METHODS: DCE-MRI and IFP
      measurements were performed of cervical tumors of 32 patients prior to therapy.
      Median tumor rk(trans) and rv(e) were derived from a bidirectional two
      compartment model using an input function derived from muscle. Median IAUC(60m)
      was defined as the integral of tumor enhancement in the first 60 seconds divided
      by the similar muscle enhancement integral. These parameters were correlated with
      the mean tumor IFP. RESULTS: There was a significant negative correlation between
      IAUC(60m) and IFP (r = -0.42, P = 0.016) and between rk(trans) and IFP (r = 
      0.47, P = 0.008). The was no significant correlation between IFP and rv(e).
      CONCLUSION: There is a moderate negative correlation between IAUC(60m),
      rk(trans), and IFP in cervical cancer. This suggests that these parameters may be
      of value in assessment of tumor behavior.

PMID- 17173304
TI  - Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic
      administration of MnCl2: changes in T1 relaxation times during postnatal
      development.
AB  - PURPOSE: To measure regional T(1) changes in the postnatal rat brain following
      systemic administration of the contrast agent manganese chloride (MnCl(2)).
      MATERIALS AND METHODS: MnCl(2) (120 mM) was administered intravenously (i.v.) at
      1.25 mL/hour to a dose of 175 mg/kg body weight. MRI experiments were performed
      on anaesthetized animals (32 male Wistar rats, postnatal days (PDs) 11, 16, 21,
      and 31) at 2.0 T. Regions of interest (ROIs) were drawn in sagittal slices and
      placed over five brain regions: olfactory bulb, cerebellum, cortex, thalamus, and
      hypothalamus. The signal intensities of each ROI were measured and fitted to a
      three-parameter function to estimate T(1) values. RESULTS: In the brains of
      animals who did not receive the contrast agent (control group), we observed a
      consistent age-dependent decrease in T(1) values. In the brains of manganese
      infused animals (manganese group), however, T(1) values were significantly lower
      than in the control group, indicating the uptake of manganese, but no dependence
      of T(1) on age was found. CONCLUSION: Our T(1) measurements indicate that the
      relative Mn(2+) concentrations are higher in neonates and decrease with brain
      development. An estimate of the relative cortical concentration of manganese
      shows a two-fold drop from PD 11 to PD 31.

PMID- 17173305
TI  - Pitfall in sputum cytology: protoctista resembling adenocarcinoma cells.

PMID- 17173306
TI  - Conformational changes upon calcium binding and phosphorylation in a synthetic
      fragment of calmodulin.
AB  - We have recently investigated by far-UV circular dichroism (CD) the effects of
      Ca(2+) binding and the phosphorylation of Ser 81 for the synthetic peptide CaM
      [54-106] encompassing the Ca(2+)-binding loops II and III and the central alpha
      helix of calmodulin (CaM) (Arrigoni et al., Biochemistry 2004, 43, 12788-12798).
      Using computational methods, we studied the changes in the secondary structure
      implied by these spectra with the aim to investigate the effect of Ca(2+) binding
      and the functional role of the phosphorylation of Ser 81 in the action of the
      full-length CaM. Ca(2+) binding induces the nucleation of helical structure by
      inducing side chain stacking of hydrophobic residues. We further investigated the
      effect of Ca(2+) binding by using near-UV CD spectroscopy. Molecular dynamics
      simulations of different fragments containing the central alpha-helix of CaM
      using various experimentally determined structures of CaM with bound Ca(2+)
      disclose the structural effects provided by the phosphorylation of Ser 81. This
      post-translational modification is predicted to alter the secondary structure in
      its surrounding and also to hinder the physiological bending of the central helix
      of CaM through an alteration of the hydrogen bond network established by the side
      chain of residue 81. Using quantum mechanical methods to predict the CD spectra
      for the frames obtained during the MD simulations, we are able to reproduce the
      relative experimental intensities in the far-UV CD spectra for our peptides.
      Similar conformational changes that take place in CaM [54-106] upon Ca(2+)
      binding and phosphorylation may occur in the full-length CaM.

PMID- 17173307
TI  - Quantitative evaluation of the effect of propylene glycol on BBB permeability.
AB  - PURPOSE: To establish the blood-brain barrier (BBB) blocking property of
      propylene glycol (PG) using the (14)C sucrose technique, quantitatively evaluate
      the effect of PG on BBB permeability using an MRI technique based on graphical
      analysis, and demonstrate the sensitivity of MRI for testing newer
      investigational drugs. MATERIALS AND METHODS: Brain uptake of sucrose was
      measured in treated (PG+) and untreated (PG-) rats using a (14)C sucrose
      technique in rat brains (N = 10) that had undergone two hours of middle cerebral
      artery occlusion (MCAO) and three hours of reperfusion. Another group of PG+ and
      PG- rats (N = 8) underwent MRI. T2-weighted (T2W) and diffusion-weighted (DW)
      images were acquired on a 4.7T MR system. A rapid T1 mapping protocol was
      implemented to acquire a baseline data set followed by postinjection data sets at
      regular intervals. The data were postprocessed pixelwise to generate permeability
      coefficient color maps. RESULTS: A significant (P < 0.05) reduction in (14)C
      sucrose space was observed on the ischemic side of PG+ rats only. Permeability
      coefficient estimates obtained by MRI from the ipsilateral hemisphere in PG+ rats
      were significantly lower than those in PG- rats (P < 0.05). There was no
      significant change on the contralateral side in PG+ rats. The results show that
      PG protects the BBB in ischemic stroke, and MRI measurements are sufficiently
      sensitive to noninvasively detect small drug effects. CONCLUSION: MRI is useful
      for evaluating the BBB blocking effect of PG in an ischemic stroke model of rat
      brain. The results from the MR experiment agree well with findings from the (14)C
      sucrose technique.

PMID- 17173308
TI  - Simulation of beta-depsipeptides: the effect of missing hydrogen-bond donors on
      their folding equilibria.
AB  - beta-Depsipeptides are beta-peptides in which one or more peptide linkages are
      replaced by ester linkages, resulting in a loss of a hydrogen-bond donor (N--H)
      and weakening of the corresponding carbonyl hydrogen-bond acceptor moiety. The
      effects of three of such peptide by ester substitutions in a hepta-beta-peptide
      upon its (un)folding equilibrium in methanol solution are investigated using
      molecular dynamics simulations and compared to experimental data from NMR
      spectroscopy. The simulated conformational ensembles largely reproduce the
      experimentally measured NOE and 3J-coupling constant data for the three different
      hepta-beta-peptides, and confirm the relative stabilities of the 3(14)-helical
      conformation, which is most weakened by substitution of the 4th peptide linkage
      and least by substitution of the 6th peptide linkage. The simulations are
      complementary to the experimental data by providing detailed insight into the
      conformational distributions that are compatible with the experimentally measured
      average values of observables.

PMID- 17173310
TI  - Five-dimensional MRI incorporating simultaneous resolution of cardiac and
      respiratory phases for volumetric imaging.
AB  - PURPOSE: To develop a new volumetric imaging method resolved over both the
      cardiac and respiratory cycles, to enable future physiological and
      pathophysiological studies of respiratory-related cardiac motion. MATERIALS AND
      METHODS: An acquisition scheme is proposed whereby the k-space acquisition order
      is controlled in real-time by the current cardiac and respiratory phases. To
      reduce eddy-current effects induced by sudden jumps in k-space, the acquisition
      order is further optimized by the use of a Hilbert curve trajectory in the k(y)
      k(z) plane. A complete three-dimensional (3D) k-space is acquired for all
      combinations of cardiac and respiratory phases, yielding a five-dimensional (5D)
      data set after retrospective reconstruction. RESULTS: Left (LV) and right
      ventricular (RV) wall excursion was measured in a healthy volunteer. Diastolic LV
      diameter was shown to increase during expiration and decrease during inspiration,
      as expected from previous echocardiography studies. The LV volume was estimated
      for all cardiac and respiratory phases with the use of a fully 3D segmentation
      tool. The results confirmed that the diastolic LV volume increased during
      expiration and decreased during inspiration. CONCLUSION: With its ability to
      measure motion anywhere in the heart, the described technique provides a
      promising approach for in-depth description of interventricular coupling,
      including 3D ventricular volumes, during both the cardiac and respiratory cycles.

PMID- 17173309
TI  - Dynamic contrast-enhanced MRI study of male pelvic perfusion at 3T: preliminary
      clinical report.
AB  - PURPOSE: To detect male pelvic perfusion in patients with coronary artery disease
      (CAD) vs. controls by dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) at 3T. MATERIALS AND METHODS: Eighteen male patients were studied with T1
      weighted (T1W) DCE-MRI to measure perfusion, phase-contrast (PC) imaging to
      measure bulk flow, and contrast-enhanced (CE)-MRA to detect stenosis. Regions of
      interest (ROIs) in prostate, corpus cavernosal, and spongiosal tissues were
      analyzed. Two-compartment pharmacokinetic modeling was employed to fit the signal
      enhancement. Perfusion parameters were analyzed by curve-fitting and utilized to
      compare the CAD and control groups. Validated questionnaires measuring urinary
      and erectile function were used to evaluate pelvic symptomatology in both groups.
      RESULTS: Mean perfusion analysis confirmed weaker and slower enhancement in CAD
      patients vs. controls despite equivalent cardiac output values. The mean maximum
      enhancement was 26.33 +/- 0.12 (controls) vs. 22.38 +/- 0.44 (CAD) for prostate.
      The mean wash-in rate in units of minute(-1) was 62.10 +/- 1.74 (controls) vs.
      34.44 +/- 1.08 (CAD) for prostate, 16.68 +/- 0.72 (controls) vs. 8.04 +/- 0.36
      (CAD) for spongiosal, and 8.34 +/- 0.54 (controls) vs. 3.48 +/- 0.24 (CAD) for
      cavernosal tissues (all with P < 0.0001). CONCLUSION: This preliminary study
      demonstrates that perfusion parameters differ between CAD and control patients,
      and the findings mirror the differences in pelvic symptoms in these groups.

PMID- 17173311
TI  - Characterization of breast lesions using the 3D FIESTA sequence and contrast
      enhanced magnetic resonance imaging.
AB  - PURPOSE: To determine whether combining 3D fast imaging employing steady-state
      acquisition (FIESTA) and T1-weighted contrast-enhanced (CE) sequences could help
      characterize lesions in 32 women with benign, in situ, or invasive breast
      lesions. Since FIESTA provides both T1 and T2 information on the same three
      dimensional (3D) matrix as high-resolution T1-weighted dynamic data, we aimed to
      verify whether invasive lesions could be separated from in situ and/or benign
      lesions using quantitative FIESTA measures of tissue intensity and homogeneity.
      MATERIAL AND METHODS: With the use of CE-MRI data, regions of interest (ROIs)
      were manually delineated in enhancing lesions and on surrounding normal tissue.
      These ROIs were then applied to 3D FIESTA data. Quantitative measures between
      lesion and normal tissue were compared among the lesion groups. RESULTS: On
      FIESTA most invasive cancer lesions were hypointense compared to surrounding
      normal tissue (mean lesion intensity was 89% of normal tissue intensity), whereas
      most ductal and benign lesions appeared hyperintense compared to surrounding
      normal tissue (lesions at 100.9% and 121.9% of normal tissue intensity,
      respectively). Measures obtained from resampled T2-weighted data showed no
      significant differences between the invasive and benign lesion groups.
      CONCLUSION: We detected significant differences between invasive and noninvasive
      lesions by quantifying intensity differences between the lesions and surrounding
      normal tissue on FIESTA.

PMID- 17173312
TI  - In vivo brain edema classification: New insight offered by large b-value
      diffusion-weighted MR imaging.
AB  - PURPOSE: To assess the role of large b-value diffusion weighted imaging (DWI) in
      the characterization of the physicochemical properties of the water in brain
      edema under experimental and clinical conditions. MATERIALS AND METHODS:
      Vasogenic brain edema was induced in mice by means of cold injury. A total of 17
      patients with extensive peritumoral brain edema were also investigated. The
      longitudinal relaxation time (T(1)) and apparent diffusion coefficient (D) were
      measured in the edematous area both in humans and in mice. D was calculated by
      using both mono- (D(mono)) and biexponential (D(fast) and D(slow)) approaches in
      the low and overall range of b-values, respectively. The D values were correlated
      with the T(1) values. RESULTS: A strong linear correlation was found between T(1)
      and D(mono) in vasogenic brain edema, both in humans and in mice. After breakdown
      of D(mono) into fast and slow diffusing components, only D(fast) exhibited a
      strong correlation with T(1); D(slow) was unchanged in vasogenic brain edema.
      CONCLUSION: Large b-value DWI can furnish a detailed characterization of
      vasogenic brain edema, and may provide a quantitative approach for the
      differentiation of edema types on the basis of the physicochemical properties of
      the water molecules. Application of the DWI method may permit prediction and
      follow-up of the effects of antiedematous therapy.

PMID- 17173313
TI  - Patent foramen ovale: standards for a preclinical model of prevalence, structure,
      and histopathologic comparability to human hearts.
AB  - BACKGROUND: This study evaluated and standardized a Patent Foramen Ovale (PFO)
      preclinical model in gross anatomic and histopathologic features. METHODS: We
      examined 150 necropsy-derived domestic porcine hearts, age 4-6 months for PFO
      prevalence, appearance, and size. Histopathologic preparations were standardized
      and processed identically to 24 post-mortem human hearts aged 16-62 years. A
      measurement scheme was developed for PFO atrial openings, tunnel length, and
      histopathologic features to compare porcine and patient hearts. RESULTS: PFO was
      found in 32 of the 150 porcine hearts (prevalence 21.3%). Twenty-five porcine PFO
      underwent standard characterization by tunnel length, and right, and left atrial
      orifice diameters. Logarithmic regression analysis between porcine PFO tunnel
      length and left atrial orifice area demonstrated a significant positive
      relationship (P = 0.0162, R(2) = 0.227). The porcine PFO tunnel length was
      significantly longer than in humans (12.0 +/- 4.0 mm vs. 7.1 +/- 3.1 mm
      respectively, P < 0.0001). Histopathologic comparison was made using serial
      sections perpendicular to the atrial septum and the tunnel long axis. Human and
      porcine PFO lesions demonstrated strong similarities in tissue cells, connective
      tissue, and matrix composition. CONCLUSIONS: PFO assessment was standardized in
      both macroscopically and histopathologically, with quantitative and qualitative
      comparisons feasible using a porcine preclinical model. PFO prevalence in
      domestic swine is identical to humans, and microscopic structures very similar to
      humans. The domestic swine PFO model appears useful to evaluate new
      interventional closure technologies due to comparability in microscopic features.
      Tunnel length should be carefully evaluated due to differences across pigs and
      patients.

PMID- 17173314
TI  - Multidetector CT coronary angiography: where we are, and where we are going...

PMID- 17173315
TI  - Psychotherapy in light of internal multiplicity.
AB  - The view that the self has multiple parts and that these appear in people seeking
      psychotherapy--and people conducting psychotherapy--is shared by clinicians of
      various orientations and supported by psychological research. It is useful for
      clinicians to think of patients as multifaceted and pay attention to the changes
      between facets that occur during therapy. They can thus help hidden parts to
      surface, facilitate dialogue between parts not in contact with each other, and
      convince excessively dominant or oppressive parts to make room for other adaptive
      facets. The authors contributing to this issue of Journal of Clinical Psychology:
      In Session describe, from their different theoretical perspectives, how they deal
      with patients' and therapists' inner multiplicity in clinical practice.

PMID- 17173316
TI  - The dialogical self in psychotherapy for persons with schizophrenia: a case
      study.
AB  - Schizophrenia often involves a profound experience of one's identity as
      diminished, which complicates adaptation to the demands of daily life. Within a
      backdrop of dialogical self-theory, we provide a report of an individual
      psychotherapy over the course of 4 years that assisted a patient suffering from
      schizophrenia to move from a state in which few aspects of self were available
      for internal or external conversation to one in which there was greater
      accessibility of multiple aspects of self, leading to richer dialogues, improved
      function, and a better quality of life. It is suggested a primary intervention of
      the therapist was continuously to offer the client a view of himself that invited
      him to experience himself in a plausible manner shared with and listened to by
      another.

PMID- 17173317
TI  - Reaching the covert, fragile side of patients: the case of narcissistic
      personality disorder.
AB  - A multifaceted self allows selection of those sides that are most suited to a
      situation and an interpersonal context, thus improving adaptation. Patients
      suffering from personality disorders display a limited range of self-aspects, and
      their relationships are stereotyped and maladaptive. Another problem is that some
      of these sides scarcely reach consciousness and usually remain in the background.
      In the case of narcissistic personality disorder (NPD) the self-part that is
      fragile is unlikely to reach consciousness, so that people suffering from this
      disorder are impervious and detached. We present a case of a psychotherapist
      working with a woman suffering from NPD by facilitating the emergence of the
      fragile part of her self, hidden by angry and scornful characters. We
      demonstrate, moreover, how reaching such a self-part is associated with an
      improvement in the patient's interpersonal relationships outside the consulting
      room.

PMID- 17173318
TI  - Submissive voices dominate in depression: assimilation analysis of a helpful
      session.
AB  - Using the assimilation model, we describe a theoretical paradox in which
      interpersonally assertive parts of the depressed person's personality are
      dominated and suppressed by parts that are interpersonally submissive and
      passive. We examine the relevance of this paradox to therapeutic work, focusing
      on a particularly helpful session (according to the therapist) from the case of
      Joan, a woman seen for depression in cognitive-behavioral therapy. We consider
      how the therapist intervened to enhance communication between the interpersonally
      submissive and dominant parts of Joan and discuss the implications of this
      process for therapy with such clients.

PMID- 17173319
TI  - Multiplicity of selves and others: cognitive analytic therapy.
AB  - In cognitive analytic therapy (CAT), multiplicity is understood in terms of a
      range of self-other patterns (reciprocal role relationships) originating in
      childhood. These alternate in determining experience and action according to the
      situation (contextual multiplicity). They may be restricted by adverse childhood
      experiences (diminished multiplicity), and severe deprivation or abuse may result
      in a structural dissociation of self-processes ( pathological multiplicity).
      Therapeutic interventions, to be effective, must be based on an understanding of
      the structure of the individual patient's self-processes. In CAT practice,
      descriptions of dysfunctional relationship patterns and of transitions between
      them are worked out by therapist and patient at the start of therapy and are used
      by both throughout its course. This approach is illustrated by an account of the
      treatment of a depressed and anxious 70-year-old man who alternated between two
      main patterns.

PMID- 17173320
TI  - Use of p63 for distinction of glandular versus squamous lesions in cervicovaginal
      specimens.
AB  - BACKGROUND: Differentiating primary glandular from high-grade squamous
      intraepithelial lesions (HSIL) that involve endocervical glands is not an
      uncommon diagnostic problem in liquid-based gynecological cytology. Squamous and
      atypical glandular cell lesions may show similar cytomorphologic features. The
      aim of this study was to evaluate the use of p63 as a marker of basal and/or
      squamous cell derivation in this differential diagnosis. METHODS: Of 59,257
      liquid-based cervicovaginal specimens collected over a 3-year period, 149 were
      diagnosed as atypical glandular cells of uncertain significance (AGUS) or
      adenocarcinoma and had histological follow-up. Ten cases (8AGUS and 2
      adenocarcinomas) were proven to be high-grade dysplasia on cervical biopsies and
      the remaining cases represented glandular pathology. Slides from discrepant cases
      were stained with p63 antibody. In addition, the authors stained 25 control cases
      (10 adenocarcinomas, 10 HSIL, and 5 negative cervicovaginal specimens). RESULTS:
      In all 10 discrepant cases, the abnormal groups originally interpreted as
      glandular in origin showed a homogeneous strong nuclear staining for p63 that
      indicated their squamous origin. Nuclei of isolated HSIL cells and basal cells
      from atrophic smears were also positive for p63. Benign and malignant glandular
      cells were uniformly negative. Isolated metaplastic, intermediate, and
      superficial squamous cells were likewise negative for this antibody. CONCLUSIONS:
      p63 is a useful immunocytochemical marker for differentiating primary glandular
      pathology from HSIL in cervicovaginal specimens. It also detects isolated HSIL
      cells ("litigation cells"). This antibody is not expressed in AGUS,
      adenocarcinoma, or normal glandular cells. p63 stains basal cells and may be a
      diagnostic pitfall in atrophic cervicovaginal specimens.

PMID- 17173321
TI  - Cystic pancreatic endocrine tumor: a variant commonly confused with cystic
      adenocarcinoma.
AB  - BACKGROUND: Most cystic pancreatic neoplasms are currently evaluated by an
      endoscopic ultrasound-guided fine-needle aspiration biopsy (FNAB). In the
      authors' experience, FNAB of cystic pancreatic endocrine tumors (PETs) frequently
      causes diagnostic difficulties, partly because of unexpected overlapping features
      with cystic ductal adenocarcinomas. METHODS: The authors identified 5
      histologically confirmed cystic PETs that were evaluated by FNAB and compared
      their cytomorphologic features to cystic ductal adenocarcinomas (n = 5) and solid
      PETs (n = 39) of the pancreas. RESULTS: Cytologically, 2 of the aspirates of
      cystic PETs were devoid of tumor cells whereas the other 3 were variably cellular
      and composed of cohesive aggregates of monomorphic cellular elements with
      variably coarse chromatin. Tumor necrosis and nuclear membrane irregularities
      were not identified in cystic PETs. Alternatively, in contrast to PETs, cystic
      ductal adenocarcinomas were characterized by nuclear pleomorphism, nuclear
      membrane irregularities, and tumor necrosis. CONCLUSIONS: Given the clinical
      implications, awareness of cystic PETs and their deceptive cytologic features
      would assist in distinguishing these lesions from cystic ductal adenocarcinomas.

PMID- 17173323
TI  - The multistory self: why the self is more than the sum of its autoparts.
AB  - A summary is presented of both the theoretical and clinical points made by the
      contributors to this issue of Journal of Clinical Psychology: In Session on the
      multiplicity of self. It is argued that there are many theoretical and clinical
      commonalities in the diverse range of psychotherapies that have been developed
      and that have been used in work with problems in the self-concept. Core problems
      encountered in clinical practice include an apparent self-integration that is
      attained through the exclusion of important parts of the self. The key to opening
      up clients who present such problems is through the use of experienced emotions
      and the therapeutic relationship. More extreme problems in the self-concept can
      be seen in the personality and psychotic disorders, in which the self may be
      chaotic or disintegrated. Such clients may need help with the development of a
      reflective self that can integrate and regulate the separate parts of the self
      concept.

PMID- 17173322
TI  - Cytology of desmoplastic small round-cell tumor: comparison of pre- and post
      chemotherapy fine-needle aspiration biopsies.
AB  - BACKGROUND: Desmoplastic small round-cell tumor (DSRCT) is an aggressive
      malignancy of young adults, which is amenable to fine-needle aspiration biopsy
      (FNAB). As this entity is increasingly recognized and biopsied, cytopathologists
      are compelled to become familiar with the range of cytologic features of DSRCT.
      In addition, postchemotherapy tumors may be sampled to confirm disease recurrence
      before planning additional therapy. This study was designed to compare
      prechemotherapy and postchemotherapy cytomorphology of DSRCT and to evaluate for
      distinct chemotherapy-induced changes. METHODS: The authors searched their
      respective institutional databases for all DSRCT cases with an associated FNAB.
      FNAB slides, immunocytochemistry, and cytogenetic results were reviewed. RESULTS:
      Six aspirates from 5 patients were identified, 3 of which were postchemotherapy.
      The postchemotherapy cases demonstrated cytologic findings not typically
      described in DSRCTs, including prominent and conspicuous nucleoli, discohesive
      single-cell architecture, and slightly larger cell size. CONCLUSIONS:
      Cytomorphologic variability was prominent in prechemotherapy cases, and no case
      could be classified as DSRCT on cytology alone; immunohistochemistry was
      necessary for definitive diagnosis. Chemotherapy increased the spectrum of
      cytologic features. The most notable difference between the 2 groups was a
      predominantly discohesive single-cell pattern with conspicuous nucleoli in the
      postchemotherapy group, instead of the clustering pattern of medium-sized cells
      with inconspicuous nucleoli typically attributed to de novo cases reported in the
      literature.

PMID- 17173324
TI  - The prevalence of eating disorders not otherwise specified.
AB  - OBJECTIVE: Eating Disorders Not Otherwise Specified (EDNOS) represent the most
      common eating disorder diagnosed in specialized treatment settings. The purpose
      of the current study is to assess the prevalence of EDNOS in a nationwide
      community sample. METHOD: Participants were 2,028 female students, aged 12-23,
      attending public schools in the 9th to 12th grades in Portugal. Participants
      completed the Eating Disorder Examination Questionnaire in Stage 1 of the study.
      In Stage 2, we selected all the participants who met any of these criteria: (1)
      BMI < or =17.5, (2) scores > or =4 on any of the four EDE-Q Subscales, (3) a
      total EDE-Q score > or =4, or (4) the presence of dysfunctional eating behaviors.
      In Stage 2, eating disorder experts interviewed 901 participants using the Eating
      Disorder Examination. RESULTS: The prevalence of all eating disorders was 3.06%
      among young females. Prevalence for anorexia nervosa was 0.39%, for bulimia
      nervosa 0.30%, EDNOS 2.37%. CONCLUSION: EDNOS is a very common eating disorder
      and accounts for three-quarters of all community cases with eating disorders.

PMID- 17173325
TI  - Internal multiplicity in emotion-focused psychotherapy.
AB  - Emotion-focused therapy regards the client's problems as indications that the
      inner dialogue among voices of the self has become fractious, often because one
      or more voices have developed emotion schemes that are based on maladaptive
      emotions. The goal of therapy is to transform such maladaptive emotions into more
      adaptive ones. The therapist's interventions focus on facilitating the client's
      process of dialogue among the voices of the self and guiding the client toward
      experiencing of adaptive emotions. These new experiences contribute to a dynamic
      shift in the relation among the voices. A case study illustrates how a male
      client's rage and hopelessness transformed into assertiveness and tenderness as
      the various voices learned to respect and help each other within the self.

PMID- 17173326
TI  - Septohippocampal properties of N-methyl-D-aspartate-induced theta-band
      oscillation and synchrony.
AB  - Microinfusion of N-methyl-D-aspartate (NMDA) into apical dendrites of hippocampal
      CA1 pyramidal cells of urethane-anesthetized rats resulted in long lasting (20-30
      min) induction of hippocampal synchrony at the field and cellular level. Power
      but not frequency of NMDA-induced theta was significantly greater than tail pinch
      induced theta activity. This effect was antagonized by intrahippocampal infusion
      of AP5, but unaffected by i.v. atropine sulfate. During AP5 blockade tail pinch
      theta frequency and power were significantly reduced. Microinfusion of NMDA into
      the medial septum also resulted in long lasting induction of hippocampal theta
      field activity. Contrary to the results of hippocampal NMDA microinfusions,
      frequency but not power of NMDA-induced theta was significantly greater than tail
      pinch- induced theta activity. Microinfusion of AP5 into the medial septum
      significantly lowered power of tail pinch-induced theta but did not affect
      frequency. Wheel running behavior of rats induced by low levels of electrical
      stimulation of the posterior hypothalamic nucleus (PH) was completely abolished
      by microinfusion of AP5 into the medial septum, accompanied by a significant
      reduction in theta power and frequency. Wheel running and theta were maintained
      at control levels with high intensity PH stimulation. We propose that: (1) the
      glutamatergic septohippocampal projection represents a third pathway capable of
      generating hippocampal field and cellular synchrony, independent of that
      generated by the septohippocampal cholinergic and GABAergic projections, and (2)
      the septohippocampal glutamatergic projection serves to function as an interface
      between cholinergic and GABAergic modulated sensory processing Type 2 theta and
      movement related Type 1 theta.

PMID- 17173327
TI  - 2,2'-Biphosphinines and 2,2'-bipyridines in homoleptic dianionic Group 4
      complexes and neutral 2,2'-biphosphinine Group 6 d(6) metal complexes: octahedral
      versus trigonal-prismatic geometries.
AB  - The geometric and electronic structure of formally d(6) tris-biphosphinine
      [M(bp)(3)](q) and tris-bipyridine [M(bpy)(3)](q) complexes were studied by means
      of DFT calculations with the B3LYP functional. In agreement with the available
      experimental data, Group 4 dianionic [M(bp)(3)](2-) complexes (1P-3P for M=Ti,
      Zr, and Hf, respectively) adopt a trigonal-prismatic (TP) structure, whereas the
      geometry of their nitrogen analogues [M(bpy)(3)](2-) (1N-3N) is nearly octahedral
      (OC), although a secondary minimum was found for the TP structures (1N'-3N'). The
      electronic factors at work in these systems are discussed by means of an MO
      analysis of the minima, MO correlation diagrams, and thermodynamic cycles
      connecting the octahedral and trigonal-prismatic limits. In all these complexes,
      pronounced electron transfer from the metal center to the lowest lying pi* ligand
      orbitals makes the d(6) electron count purely formal. However, it is shown that
      the bp and bpy ligands accommodate the release of electron density from the metal
      in different ways because of a change in the localization of the HOMO, which is a
      mainly metal-centered orbital in bp complexes and a pure pi* ligand orbital in
      bpy complexes. The energetic evolution of the HOMO allows a simple
      rationalization of the progressive change from the TP to the OC structure on
      successive oxidation of the [Zr(bp)(3)](2-) complex, a trend in agreement with
      the experimental structure of the monoanionic complex. The geometry of Group 6
      neutral complexes [M(bp)(3)] (4P and 5P for M=Mo and W, respectively) is found to
      be intermediate between the TP and OC limits, as previously shown experimentally
      for the tungsten complex. The electron transfer from the metal center to the
      lowest lying pi* ligand orbitals is found to be significantly smaller than for
      the Group 4 dianionic analogues. The geometrical change between [Zr(bp)(3)](2-)
      and [W(bp)(3)] is analyzed by means of a thermodynamic cycle and it is shown that
      a larger ligand-ligand repulsion plays an important role in favoring the
      distortion of the tungsten complex away from the TP structure.

PMID- 17173328
TI  - Enantioselective desymmetrization of meso epoxides with anilines catalyzed by a
      niobium complex of a chiral multidentate binol derivative.

PMID- 17173329
TI  - Triplet repeat in the Repin1 3'-untranslated region on rat chromosome 4
      correlates with facets of the metabolic syndrome.
AB  - BACKGROUND: Congenic and subcongenic rat strains confirmed the quantitative trait
      loci (QTLs) for facets of the metabolic syndrome between 60.53 and 77.11 Mb on
      chromosome 4. The analysis of candidate genes in this region favoured the
      replication initiator 1 (Repin1) characterized by a SNP in the coding region and
      a triplet repeat (TTT) in the 3'-untranslated region (3'UTR). METHODS: We
      analysed nine rat strains (BB/OK, SHR, F344, BN, DA, LEW, hHTg, WOKW, and their
      founders WOK-F) and four wild rats on DNA (sequencing) and RNA level (gene
      expression in blood, liver, subcutaneous, and epididymal adipocytes). In
      addition, the rats were phenotypically characterized in order to link the rat
      phenotype to genotype differences in the QTL on chromosome 4. RESULTS: Wild rats
      were heterozygous for the SNP (C/T), whereas all the inbred strains were
      homozygous. The shortest triplet repeat was found in SHR (5) and the highest was
      found in hHTg and WOKW (11), which developed metabolic disorders. The repeat
      number correlated with most phenotypic traits studied. Using linear multiple
      regression analysis with repeat size as the dependent variable and considering
      all the data of this study, it was clearly demonstrated that not only VLDL
      cholesterol and serum insulin but also the expression of Repin1 in the liver is
      significantly associated with the repeat size of the 3'UTR. CONCLUSIONS: It is
      concluded that the triplet repeat expansion in 3'UTR is involved in metabolic
      alterations as found in hHTg and WOKW rats and that the functional unknown gene,
      Repin1, could be a novel candidate gene for the development of facets of the
      metabolic syndrome.

PMID- 17173330
TI  - Cloning, characterization and expression of a calnexin homologue from the
      pathogenic fungus Paracoccidioides brasiliensis.
AB  - We report the cloning of a Paracoccidioides brasiliensis cDNA, here named PbCnx,
      encoding the homologue of the endoplasmic reticulum molecular chaperone calnexin.
      Calnexin specifically recognizes monoglucosylated glycoproteins in the
      endoplasmic reticulum, thus being an essential component of the complex that
      interacts with the folded state of nascent secreted glycoproteins. The PbCnx open
      reading frame was found in a 1701 base pair (bp) fragment that encodes a 567
      amino acid protein with an estimated mass of 62 680 Da. Northern and Southern
      blot hybridizations showed that PbCnx is encoded by a single, or a low number of,
      gene copies. PbCnx contains the hallmark KPEDWD motifs that are found in all
      members of the calnexin/calreticulin family proteins. A cDNA-encoding PbCnx was
      overexpressed as recombinant protein in Escherichia coli. The purified
      recombinant PbCnx was recognized by 6 out of 10 sera from PCM patients, a result
      that rules out its possible consideration for further use in diagnosis. Using
      confocal microscopy with anti-PbCnx mouse serum against yeast forms, a
      cytoplasmic staining pattern was observed.

PMID- 17173331
TI  - Lyn, one of the Src-family tyrosine kinases expressed in phagocytes, plays an
      important role in beta2 integrin-signalling pathways in opsonized zymosan
      activated macrophage-like U937 cells.
AB  - We have investigated the contribution of Hck, Lyn and Fgr, highly expressed Src
      family tyrosine kinases (SFKs) in signalling pathways in opsonized zymosan (OZ)
      activated phagocytes by using short interfering RNAs (siRNAs). Treatment of
      macrophage-like U937 cells with the siRNAs targeted to these transcripts
      decreased the protein content of each kinase to less than half that of untreated
      cells. Among these siRNAs, siRNA targeted to Lyn was the most effective in
      diminishing two kinds of phagocyte functions, that is oxidative burst and
      phagocytosis. Phosphorylation of c-Cbl, a multidomain adaptor protein in the
      beta2 integrin-signalling pathway, was also largely inhibited by treatment with
      siRNA to Lyn. Thus, the results with siRNAs highly specific for Hck, Lyn and Fgr
      suggested that, among these three SFKs, Lyn plays the most important role in
      signalling pathways downstream of beta2 integrins in OZ-stimulated phagocytes.

PMID- 17173332
TI  - Cloning of an epoxide hydrolase-encoding gene from Rhodotorula mucilaginosa and
      functional expression in Yarrowia lipolytica.
AB  - Epoxide hydrolases (EHs), especially those of fungal origin, have the ability to
      catalyse the enantioselective hydrolysis of epoxides to their corresponding
      diols. Recombinant DNA technology has been used extensively to overproduce these
      catalysts for the efficient hydrolytic kinetic resolution of epoxides, which
      serve as high-value intermediates in the fine chemicals and pharmaceutical
      industries. Degenerate primers, based on data from available EH-encoding gene
      sequences, in conjunction with inverse PCR, were used to amplify the genomic EH
      encoding gene from Rhodotorula mucilaginosa. The 2347 bp genomic sequence
      revealed a 1979 bp ORF containing nine introns. The cDNA sequence revealed an
      1185 bp EH-encoding gene that translates into a 394 amino acid protein exhibiting
      low sequence homology towards the known EH proteins. The EH gene from R.
      mucilaginosa was functionally expressed in Yarrowia lipolytica using a
      constitutive integrative expression cassette. Whole-cell biotransformation of
      (2,3-epoxypropyl)benzene, using the recombinant EH, revealed activity and
      selectivity far superior to any other activity and selectivity reported in
      literature using wild-type organisms. The GenBank Accession No. for the R.
      mucilaginosa EH gene is AY627310.

PMID- 17173333
TI  - The ORF YNL274c (GOR1) codes for glyoxylate reductase in Saccharomyces
      cerevisiae.
AB  - The enzyme glyoxylate reductase reversibly reduces glyoxylate to glycolate, or
      alternatively hydroxypyruvate to D-glycerate, using either NADPH or NADH as a co
      factor. The enzyme has multiple metabolic roles in different organisms. In this
      paper we show that GOR1 (ORF YNL274c) encodes a glyoxylate reductase and not a
      hydroxyisocaproate dehydrogenase in Saccharomyces cerevisiae, even though it also
      has minor activity on alpha-ketoisocaproate. In addition, we show that deletion
      of the glyoxylate reductase-encoding gene leads to higher biomass concentration
      after diauxic shift.

PMID- 17173334
TI  - In Schizosaccharomyces pombe the 14-3-3 protein Rad24p is involved in negative
      control of pho1 gene expression.
AB  - Expression of Schizosaccharomyces pombe pho1-encoded acid phosphatase is
      transcriptionally regulated by adenine and phosphate. Four genes, anr1-3 and
      anr5, encode negative regulators of pho1 expression. Apart from being designated
      as loci, the anr genes have not been further characterized. In this study we
      provide evidence that a strain carrying the deletion of rad24, a 14-3-3 protein
      encoding gene, exhibits an anr mutant like the phenotype (higher phosphatase
      activity, higher transcript levels of pho1, lower sensitivity to adenine of pho1
      expression) and that rad24 is closely linked, probably allelic, to anr5. By
      sequencing the two exons of the rad24 gene in a strain carrying the mutant allele
      anr5-13, we found a T/A-to-C/G transition in the 225th codon of its ORF, causing
      a leucine-to-serine substitution in a highly conserved region of all proteins of
      the 14-3-3 family. anr2 and anr3 are not allelic to rad24. The mutant alleles of
      anr2 and anr3 are recessive to their wild-type alleles and do not belong to the
      same epistasis group as rad24.

PMID- 17173335
TI  - Selection-by-function: efficient enrichment of cathepsin E inhibitors from a DNA
      library.
AB  - A method for efficient enrichment of protease inhibitors out of a DNA library was
      developed by introducing SF-link technology. A two-step selection strategy was
      designed consisting of the initial enrichment of aptamers based on binding
      function while the second enrichment step was based on the inhibitory activity to
      a protease, cathepsin E (CE). The latter was constructed by covalently linking of
      a biotinylated peptide substrate to each of the ssDNA molecule contained in the
      preliminarily selected DNA library, generating 'SF-link'. Gradual enrichment of
      inhibitory DNAs was attained in the course of selection. One molecule, SFR-6-3,
      showed an IC(50) of around 30 nM, a K(d) of around 15 nM and high selectivity for
      CE. Sequence and structure analysis revealed a C-rich sequence without any
      guanine and possibly an i-motif structure, which must be novel to be found in in
      vitro-selected aptamers. SF-link technology, which is novel as the screening
      technology, provided a remarkable enrichment of specific protease inhibitors and
      has a potential to be further developed.

PMID- 17173336
TI  - Study of methylation of nitrogen-containing compounds in the gas phase.
AB  - The methyl migration between the protonated N,N-dimethylisopropylamine and other
      neutral aliphatic amines in the gas phase has been investigated by a hybrid
      external chemical ionization source ion trap mass spectrometer. Similar reactions
      have been found in the aqueous solution by Callahan and Wolfenden (J. Am. Chem.
      Soc. 2003; 125: 310). At the same time, density functional theory (DFT)
      calculations show that in contrast with the neutral N,N-dimethylisopropylamine,
      protonated N,N-dimethylisopropylamine is a better methyl donor. These results
      indicate that protonation promotes the methyl migration between aliphatic amines
      both in the gas phase and in the aqueous solution. In addition, methyl transfer
      also exists between the protonated N,N-dimethylisopropylamine and some other
      nitrogen-containing compounds.

PMID- 17173337
TI  - Isomeric identification by laser control mass spectrometry.
AB  - The influence shaped femtosecond laser pulses have on molecular
      photofragmentation and ionization, coupled with the intrinsic sensitivity of mass
      spectrometry, results in a powerful tool for fast, accurate, reproducible and
      quantitative isomeric identification. Complex phase functions are introduced to
      enhance differences during the laser-molecule interactions, which depend on
      geometric structure, resulting in different fragmentation fingerprints. A full
      account is given on the setup and results leading to a technique that can be used
      to distinguish between compounds normally indistinguishable by conventional
      electron ionization mass spectrometry. We demonstrate geometric and structural
      isomer identification of cis-/trans-3-heptene, cis-/trans-4-methyl-2-pentene, o
      /p-cresol and o-/p-xylene. For the positional isomers of xylene we present a
      complete dataset consisting of 1024 different phases to explore phase complexity.
      A selection of two phases from that data can then be used to achieve quantitative
      identification in mixtures of xylene isomers. Finally, we evaluate receiver
      operational curves obtained from our experimental data to demonstrate the
      reliability that can be achieved by femtosecond laser control mass spectrometry.

PMID- 17173338
TI  - High-performance liquid chromatography-electrospray ionization mass spectrometry
      determination of mitiglinide in human plasma and its pharmacokinetics.
AB  - A selective and sensitive method employing high-performance liquid chromatography
      electrospray ionization mass spectrometry was developed and validated for the
      determination of mitiglinide in human plasma.With gliclazide as the internal
      standard, mitiglinide was extracted from plasma with n-hexane: = 80 : 20 (v/v).
      The organic layer was evaporated and the residue was redissolved in methanol:
      water (10 mM CH3COONH4, pH = 3.0) = 65 : 35 (v/v). An aliquot of 10 microl was
      chromatographically analyzed on a prepacked Shimadzu VP-ODS (5 microm, 150 x 2.0
      mm i.d.) using the mobile phase comprising methanol: water (10 mM CH3COONH4) = 65
      : 35 (v/v) by means of selected-ion monitoring mode mass spectrometry. Standard
      curves were linear (r2 = 0.9972) over the concentration range of 2.84-11 300
      pmol/ml and had good accuracy and precision. The within- and between-batch
      precisions of the method were within 15% of standard deviation. The lower limit
      of detection was 1.42 pmol/ml. The validated HPLC/ESI-MS method has been
      successfully applied in the pharmacokinetics of mitiglinide in 12 healthy Chinese
      volunteers.

PMID- 17173339
TI  - Monte Carlo probabilistic sensitivity analysis for patient level simulation
      models: efficient estimation of mean and variance using ANOVA.
AB  - Probabilistic sensitivity analysis (PSA) is required to account for uncertainty
      in cost-effectiveness calculations arising from health economic models. The
      simplest way to perform PSA in practice is by Monte Carlo methods, which involves
      running the model many times using randomly sampled values of the model inputs.
      However, this can be impractical when the economic model takes appreciable
      amounts of time to run. This situation arises, in particular, for patient-level
      simulation models (also known as micro-simulation or individual-level simulation
      models), where a single run of the model simulates the health care of many
      thousands of individual patients. The large number of patients required in each
      run to achieve accurate estimation of cost-effectiveness means that only a
      relatively small number of runs is possible. For this reason, it is often said
      that PSA is not practical for patient-level models. We develop a way to reduce
      the computational burden of Monte Carlo PSA for patient-level models, based on
      the algebra of analysis of variance. Methods are presented to estimate the mean
      and variance of the model output, with formulae for determining optimal sample
      sizes. The methods are simple to apply and will typically reduce the
      computational demand very substantially.

PMID- 17173340
TI  - Dementia care mapping as a research tool.
AB  - INTRODUCTION: Dementia Care Mapping (DCM) was originally developed as a clinical
      tool but has attracted interest as a potential observational measure of quality
      of life (QOL) and well-being of long-term care residents with dementia. DCM
      coding involves continuous observation over a 6-h period, with observers
      recording a Behavior Category Code (BCC, a recording of activity/interaction) and
      a Well/Ill Being (WIB) score at 5 min intervals. METHOD: Descriptive data from
      several different research teams on the distribution and psychometric properties
      of DCM data were compiled and summarized. RESULTS: Issues and problems identified
      include: complex scoring algorithms, inter-rater reliability of the BCCs, limited
      variability of WIB values, associations between resident characteristics and DCM
      assessments, rater time burden, and comparability of results across study
      settings. CONCLUSIONS: Despite the identified limitations, DCM has promise as a
      research measure, as it may come closer to rating QOL from the perspective of
      persons with dementia than other available measures. Its utility will depend on
      the manner in which it is applied and an appreciation of the measure's strength
      and limitations. Possible changes that might improve the reliability, validity,
      and practicality of DCM as a research tool include coding the predominant event
      (rather than the 'best' event), shortening the observation period, and adding '0'
      as a neutral WIB coding option.

PMID- 17173342
TI  - Bayesian analysis of non-homogeneous Markov chains: application to mental health
      data.
AB  - In this paper we present a formal treatment of non-homogeneous Markov chains by
      introducing a hierarchical Bayesian framework. Our work is motivated by the
      analysis of correlated categorical data which arise in assessment of psychiatric
      treatment programs. In our development, we introduce a Markovian structure to
      describe the non-homogeneity of transition patterns. In doing so, we introduce a
      logistic regression set-up for Markov chains and incorporate covariates in our
      model. We present a Bayesian model using Markov chain Monte Carlo methods and
      develop inference procedures to address issues encountered in the analyses of
      data from psychiatric treatment programs. Our model and inference procedures are
      implemented to some real data from a psychiatric treatment study.

PMID- 17173345
TI  - Effect of substituents at the 5-position of the pyridine ring of imidacloprid on
      insecticidal activity against Periplaneta americana.
AB  - The insecticidal activities of imidacloprid derivatives with a wide range of
      substituents at the 5-position on the pyridine ring against American cockroaches,
      Periplaneta americana (L.), were measured by injection with and without
      synergists propyl 2-propynyl phenylphosphonate and piperonyl butoxide. The
      log(1/MLD) value (MLD = minimal lethal dose in mol) without synergists was 7.96
      for the methyl derivative, and the values were lower for other derivatives.
      Synergists enhanced the potencies of all the compounds tested. Considering these
      compounds and those with other substituents at this position, the region for
      maximum activity was predicted to be in the conjunction of the pyridyl 6-chlorine
      atom with a lipophilic small group in the 5-position.

PMID- 17173344
TI  - Influence of agricultural adjuvants on droplet spectra.
AB  - The formation of a spray is the result of interaction between the nozzle type and
      the spray liquid. When adjuvants lower the surface tension, a shift to a finer
      spray quality might be expected. Increases in viscosity might cause coarser
      sprays. The spray pressure, nozzle type and spray liquid determine spray
      performance. Adjuvants that cause droplets of oil in the spray mixture, for
      example crop oils, petroleum oils and even some water-insoluble emulsifiers and
      surfactants, may unexpectedly increase the spray droplet size. In cases where a
      finer spray is obtained, the volume fraction of drops smaller than 100 microm
      diameter, V(100), is expected to increase, but for some adjuvants a decrease in
      V(100) is observed. Finally, spray droplets may also differ when the
      concentration of the applied adjuvants changes. An overview based on reports in
      the literature is given of the effects of different classes of adjuvants used for
      agricultural cropping on spray droplet spectra. The effects of these adjuvants on
      spray formation depend on the type of nozzle in combination with the applied
      pressure.

PMID- 17173346
TI  - Synergism studies with binary mixtures of pyrethroid, carbamate and
      organophosphate insecticides on Frankliniella occidentalis (Pergande).
AB  - The major mechanism of resistance to most insecticides in Frankliniella
      occidentalis (Pergande) is metabolic, piperonyl butoxide (PBO) suppressible,
      mediated by cytochrome-P450 monooxygenases and conferring cross-resistance among
      insecticide classes. The efficacy of insecticide mixtures of acrinathrin,
      methiocarb, formetanate and chlorpyrifos was studied by topical exposure in
      strains of F. occidentalis selected for resistance to each insecticide. The
      method consisted in combining increasing concentrations of one insecticide with a
      constant low rate of the second one as synergist. Acrinathrin activity against F.
      occidentalis was enhanced by carbamate insecticides, methiocarb being a much
      better synergist than formetanate. Monooxygenase action on the carbamates would
      prevent degradation of the pyrethroid, hence providing a level of synergism by
      competitive substrate inhibition. However, the number of insecticides registered
      for control of F. occidentalis is very limited, and they are needed for
      antiresistance strategies such as mosaics and rotations. Therefore, a study was
      made of the synergist effect of other carbamates not used against thrips, such as
      carbofuran and carbosulfan, against a susceptible strain and a field strain.
      Neither carbamate showed synergism to acrinathrin in the susceptible strain, but
      both did in the field strain, carbosulfan being a better synergist than
      carbofuran. The data obtained indicate that low rates of carbamates could be used
      as synergists to restore some pyrethroid susceptibility in F. occidentalis.

PMID- 17173347
TI  - Using mixed methods to evaluate the use of a caregiver strain measure to assess
      outcomes of a caregiver support program for caregivers of older adults.
AB  - PURPOSE: Many assessment tools have been developed for evaluating caregiving
      programs, but the majority are too cumbersome for ongoing use. This study reports
      on a brief assessment tool used to monitor strain among family members caring for
      an impaired elder. DESIGN AND METHODS: Participants were enrolled in the
      SeniorCare program, a program funded by the Administration on Aging to provide
      care to family caregivers. The Caregiver Risk Screen (CRS) is a 12-item measure
      of strain, initially developed as part of an in-home assessment procedure. Its
      utility for use in practice settings over time was assessed using both
      quantitative and qualitative methodology. RESULTS: Chronbach alpha levels for the
      CRS were 0.85 at intake and 0.84 at first follow-up. At the first follow-up, the
      overall index score and five of the 12 items showed statistically significant
      lessened strain. In subsequent follow-up evaluations, the average improvements
      were maintained but there was no additional decrease in strain. Individual
      variations in changes over time were identified by combining quantitative and
      qualitative information. Themes that emerged in qualitative data served to modify
      the measure for future use. IMPLICATIONS: The brief Caregiver Risk Screen tool
      appears to be a reliable and valid tool for use in practice settings. It is
      acceptable to clients and professional staff. Modifications have been made that
      may further enhance the suitability of this measure for other settings.

PMID- 17173348
TI  - Comparison of the medium molecular weight venom fractions from five species of
      common social wasps by MALDI-TOF spectra profiling.
AB  - The average spectral profiles and the exact mass weight (MW) of biomolecules
      present in the medium fraction (from 900 to 3000 Da) of the venom of five social
      wasps (three European and one North American Polistes and the European hornet
      Vespa crabro) were determined by matrix assisted laser desorption ionization time
      of flight (MALDI-TOF) MS. Data were obtained analyzing the venom of single
      specimens (N = 46) and elaborated with the ClinProTools 2.0 (CPT) software to
      search for differences among the five species examined. Interesting differences
      in the spectral profiles were found, allowing the discrimination of venoms
      belonging to the different species, and their possible use as a quality control
      method in venom immunotherapy (VIT) for allergic patients.

PMID- 17173349
TI  - Anticipating full benefits from the new papillomavirus vaccines.

PMID- 17173352
TI  - Early-life risk factors for late-onset depression.
AB  - OBJECTIVE: To assess differences between women with no history of depression (No
      MDD), early-onset depression (EOD), and late-onset depression (LOD) on
      psychosocial risk factors (marital conflict and lack of social support),
      neuroticism, and overall self-rated health. METHOD: Diagnostic data from a
      community-based longitudinal study of women at mean ages 39, 42, 48, and 59 was
      used to create three groups of women (No MDD, EOD and LOD). These groups were
      then compared on psychosocial, personality, and overall health risk assessed
      approximately 10 years prior to diagnosis. RESULTS: There were no differences
      between the groups on marital conflict and social support. Those with EOD scored
      higher than those in the LOD and No MDD groups on neuroticism. Importantly, those
      with LOD reported poorer health than those with No MDD 10 years prior to
      diagnosis. CONCLUSIONS: These findings provide support for the notion that poor
      health and not psychosocial risk factors or neuroticism predispose otherwise
      healthy adults to developing depression for the first time in late-life.

PMID- 17173353
TI  - Prevalence of cognitive and functional impairment in a community sample in
      Ribeirao Preto, Brazil.
AB  - OBJECTIVE: This study aimed at estimating the prevalence of cognitive and
      functional impairment (CFI) in a community sample in Ribeirao Preto, Brazil,
      evaluating its distribution in relation to various socio-demographic and clinical
      factors. METHODS: The population was a representative sample aged 60 and older,
      from three different socio-economic classes. Cluster sampling was applied.
      Instruments used to select CFI (a syndromic category that does not exclude
      dementia): 'Mini Mental State Examination' (MMSE), 'Fuld Object Memory
      Evaluation' (FOME), 'Informant Questionnaire on Cognitive Decline in the Elderly'
      (IQCODE), 'Bayer Activities of Daily Living Scale' (B-ADL) and clinical
      interviews. The data obtained were submitted to bivariate and logistic regression
      analysis. RESULTS: A sample of 1.145 elderly persons was evaluated, with a mean
      age of 70.9 years (60-100; DP: 7.7); 63.4% were female, and 52.8% had up to 4
      years of schooling. CFI prevalence was 18.9% (n = 217). Following logistic
      regression analysis, higher age, low education, stroke, epilepsy and depression
      were associated with CFI. Female sex, widowhood, low social class and head trauma
      were associated with CFI only on bivariate analysis. CONCLUSION: CFI prevalence
      results were similar to those found by studies in Brazil, Puerto Rico and
      Malaysia. Cognitive and functional impairment is a rather heterogeneous condition
      which may be associated with various clinical conditions found in the elderly
      population. Due to its high prevalence and association with higher mortality and
      disability rates, this clinical syndrome should receive more attention on public
      health intervention planning.

PMID- 17173354
TI  - An intervention to improve depression care in older adults with COPD.
AB  - OBJECTIVE: To describe an intervention for older persons with Major Depressive
      Disorder (MDD) and Chronic Obstructive Pulmonary Disease (COPD) to improve
      adherence to psychiatric, medical, and rehabilitation recommendations. The
      intervention supplements antidepressant therapy for depression with an
      individualized care manager who targets psychological barriers that interfere
      with treatment participation. METHOD: Description of intervention development,
      training, and barriers to care, and illustration with case example. RESULTS:
      Depression and its associated lack of motivation, helplessness, and lack of
      energy can obstruct active participation in rehabilitation exercises recommended
      for COPD. Additionally, depressed older adults perceive the benefits of
      depression treatment; however they also fear side effects, addiction to
      antidepressants and have concerns about stigma. The intervention elucidates
      individual attitudes and beliefs that may become barriers. The care manager works
      with the older adult to address the barriers and improve treatment participation.
      CONCLUSION: Augmentation of traditional pharmacotherapy for depression with a
      care manager can improve adherence to both depression and COPD treatment. This
      improved adherence may lessen the physical, psychological, and functional costs
      of both diseases.

PMID- 17173357
TI  - Biodegradability of leachates from Chinese and German municipal solid waste.
AB  - The quantitative and qualitative composition of Chinese municipal solid waste
      (MSW) differs significantly from German waste. The focus of this paper is on
      whether these differences also lead to dissimilar qualities of leachates during
      storage or landfilling. Leachates ingredients determine the appropriate treatment
      technique. MSW compositions of the two cities Guilin (China) and Essen (Germany),
      each with approx. 600 000 inhabitants, are used to simulate Chinese and German
      MSW types. A sequencing batch reactor (SBR) is used, combining aerobic and
      anaerobic reaction principles, to test the biodegradability of leachates.
      Leachates are tested for temperature, pH-value, redox potentials, and oxygen
      concentration. Chemical oxygen demand (COD) values are determined. Within 8 h,
      the biodegradation rates for both kinds of leachates are more than 90%. Due to
      the high organic content of Chinese waste, the degradation rate for Guilin MSW
      leachate is even higher, up to 97%. The effluent from SBR technique is suitable
      for direct discharge into bodies of water.

PMID- 17173356
TI  - Assessing potential dietary toxicity of heavy metals in selected vegetables and
      food crops.
AB  - Heavy metals, such as cadmium, copper, lead, chromium and mercury, are important
      environmental pollutants, particularly in areas with high anthropogenic pressure.
      Their presence in the atmosphere, soil and water, even in traces can cause
      serious problems to all organisms, and heavy metal bioaccumulation in the food
      chain especially can be highly dangerous to human health. Heavy metals enter the
      human body mainly through two routes namely: inhalation and ingestion, ingestion
      being the main route of exposure to these elements in human population. Heavy
      metals intake by human populations through food chain has been reported in many
      countries. Soil threshold for heavy metal toxicity is an important factor
      affecting soil environmental capacity of heavy metal and determines heavy metal
      cumulative loading limits. For soil-plant system, heavy metal toxicity threshold
      is the highest permissible content in the soil (total or bioavailable
      concentration) that does not pose any phytotoxic effects or heavy metals in the
      edible parts of the crops does not exceed food hygiene standards. Factors
      affecting the thresholds of dietary toxicity of heavy metal in soil-crop system
      include: soil type which includes soil pH, organic matter content, clay mineral
      and other soil chemical and biochemical properties; and crop species or cultivars
      regulated by genetic basis for heavy metal transport and accumulation in plants.
      In addition, the interactions of soil-plant root-microbes play important roles in
      regulating heavy metal movement from soil to the edible parts of crops. Agronomic
      practices such as fertilizer and water managements as well as crop rotation
      system can affect bioavailability and crop accumulation of heavy metals, thus
      influencing the thresholds for assessing dietary toxicity of heavy metals in the
      food chain. This paper reviews the phytotoxic effects and bioaccumulation of
      heavy metals in vegetables and food crops and assesses soil heavy metal
      thresholds for potential dietary toxicity.

PMID- 17173358
TI  - Effect of calcium and light on the germination of Urochondra setulosa under
      different salts.
AB  - Urochondra setulosa (Trin.) C.E. Hubbard is a coastal halophytic grass thriving
      on the coastal dunes along the Pakistani seashore. This grass could be useful in
      coastal sand dune stabilization using seawater irrigation. The purpose of this
      investigation was to test the hypothesis that Ca(2+) (0.0, 2.5, 5.0, 10.0 and
      50.0 mmol/L) alleviates the adverse effects of KCl, MgSO(4), NaCl and Na(2)SO(4)
      at 0, 200, 400, 600, 800 and 1000 mmol/L on the germination of Urochondra
      setulosa. Seed germination was inhibited with increase in salt concentration with
      few seeds germinated at and above 400 mmol/L concentration. No seed germinated in
      any of the KCl treatments. Inclusion of CaCl(2) substantially alleviated the
      inhibitory effects of all salts. Germination was higher under photoperiod in
      comparison to those seeds germinated under complete darkness. Among the CaCl(2)
      concentrations used, 10 mmol/L was most effective in alleviating salinity effects
      and allowing few seeds to germinate at 1000 mmol/L KCl, MgSO(4), NaCl and
      Na(2)SO(4) solution.

PMID- 17173359
TI  - Optimization of fermentation conditions for P450 BM-3 monooxygenase production by
      hybrid design methodology.
AB  - Factorial design and response surface techniques were used to design and optimize
      increasing P450 BM-3 expression in E. coli. Operational conditions for maximum
      production were determined with twelve parameters under consideration: the
      concentration of FeCl(3), induction at OD(578) (optical density measured at 578
      nm), induction time and inoculum concentration. Initially, Plackett-Burman (PB)
      design was used to evaluate the process variables relevant in relation to P450 BM
      3 production. Four statistically significant parameters for response were
      selected and utilized in order to optimize the process. With the 416C model of
      hybrid design, response surfaces were generated, and P450 BM-3 production was
      improved to 57.90x10(-3) U/ml by the best combinations of the physicochemical
      parameters at optimum levels of 0.12 mg/L FeCl(3), inoculum concentration of
      2.10%, induction at OD(578) equal to 1.07, and with 6.05 h of induction.

PMID- 17173360
TI  - Oogenesis in summer females of the rice water weevil, Lissorhoptrus oryzophilus
      Kuschel (Coleoptera: Curculionidae), in southern Zhejiang, China.
AB  - The rice water weevil, Lissorhoptrus oryzophilus Kuschel, has two generations in
      southern Zhejiang, China. To determine oogenesis in first-generation females
      (summer females) and its relations to temperature, females were collected from a
      rice field in early and mid-July and reared on young rice plants at 28, 31 and 34
      degrees C in the laboratory. Percentage of females having oocytes, number of
      oocytes of different stages (stage-I, from early previtellogenesis to middle
      vitellogenesis; stage-II, late vitellogenesis; and mature-oocyte stage), and
      length of ovarioles were determined every 10 d of feeding. At each temperature,
      oogenesis took place in over 40% of females after 20~40 d of feeding, but only
      0.0~3.3 stage-I, 0.0~0.8 stage-II and 0.0~1.1 mature oocytes were observed at
      each observation date. Temperature had significant effect on number of stage-I
      oocytes but not on number of stage-II and mature oocytes in early July females;
      temperature had no significant effect on number of oocytes of either stage in mid
      July females. Conclusively, in southern Zhejiang, summer L. oryzophilus females
      have great potential to become reproductive on rice, but their oogenesis activity
      is very low, with the overall procedures little affected by temperature.

PMID- 17173361
TI  - FoxO4 is the main forkhead transcriptional factor localized in the
      gastrointestinal tracts of pigs.
AB  - Forkhead box (Fox) proteins play critical roles in the regulation of
      differentiation, proliferation, immunity and aging of cells. Most studies on Fox
      proteins are limited to cultured cells and rodent. The aim of the current study
      is to detect by immunohistrochemistry whether FoxO1, FoxO3a and FoxO4 proteins
      are localized in the stomach and intestine of the pig. The results showed that
      FoxO4 exists in the mucosa in all parts of the stomach and intestine; FoxO3a
      exists mainly in the lamina propria and muscularis of some parts. However, FoxO1
      is not detectable in all parts of the stomach and intestine. Collectively, the
      results of the present study indicate that there exists a distinct expression
      pattern of Fox proteins, and that FoxO4 is a primary forkhead transcriptional
      factor localized in the gastrointestinal tracts of the pig.

PMID- 17173362
TI  - Microwave-assisted synthesis, anticonvulsant activity and quantum mechanical
      modelling of N-(4-bromo-3-methylphenyl) semicarbazones.
AB  - OBJECTIVE: To study the effect of halo substitution on disubstituted aryl
      semicarbazones on the anticonvulsant potential and model the activity based on
      quantum mechanics. METHODS: A series of twenty-six compounds of N(4)-(4-bromo-3
      methylphenyl) semicarbazones were synthesized and evaluated for the
      anticonvulsant activity in the maximal electroshock seizure (MES) and
      subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. Some potential
      compounds were also tested in the subcutaneous strychnine (scSTY) and
      subcutaneous picrotoxin (scPIC) seizure threshold tests. The synthesized
      compounds were tested for behavioral impairment and CNS (central nervous system)
      depression in mice. Quantum mechanical modelling was carried out on these
      compounds to gain understanding on the structural features essential for
      activity. RESULTS: Some compounds possessed broad spectrum anticonvulsant
      activity as indicated by their effect in pentylenetetrazole, strychnine,
      picrotoxin and maximal electroshock seizures models in resemblance to other aryl
      semicarbazone derivatives reported earlier. The higher the difference in HOMO
      (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular
      orbital) energy levels was, the greater was the activity profile. CONCLUSION: The
      pharmacophoric requirements for compounds to exhibit anticonvulsant activity that
      includes one aryl unit in proximity to a hydrogen donor-acceptor domain and an
      electron donor have been justified with the molecular orbital surface analysis of
      the synthesized compounds.

PMID- 17173363
TI  - Comparison of the performance of chiral stationary phase for separation of
      fluoxetine enantiomers.
AB  - Separation of fluoxetine enantiomers on five chiral stationary phases (chiralcel
      OD-H, chiralcel OJ-H, chiralpak AD-H, cyclobond capital I, Ukrainian 2000 DM and
      kromasil CHI-TBB) was investigated. The optimal mobile phase compositions of
      fluoxetine separation on each column were hexane/isopropanol/diethyl amine
      (98/2/0.2, v/v/v), hexane/isopropanol/diethyl amine (99/1/0.1, v/v/v),
      hexane/isopropanol/diethyl amine (98/2/0.2, v/v/v), methanol/0.2% triethylamine
      acetic acid (TEAA) (25/75, v/v; pH 3.8) and hexane/isopropanol/diethyl amine
      (98/2/0.2, v/v/v), respectively. Experimental results demonstrated that baseline
      separation (R(S)>1.5) of fluoxetine enantiomers was obtained on chiralcel OD-H,
      chiralpak AD-H, and cyclobond capital I, Ukrainian 2000 DM while the best
      separation was obtained on the last one. The eluate orders of fluoxetine
      enantiomers on the columns were determined. The first eluate by chiralcel OJ-H
      and kromasil CHI-TBB is the S-enantiomer, while by chiralpak AD-H and cyclobond I
      2000 DM is the R-enantiomer.

PMID- 17173364
TI  - Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism,
      present strategies and future perspectives of therapies.
AB  - Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests
      as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be
      resulted from various processes that directly or indirectly injure the lung.
      Extensive investigations in experimental models and humans with ALI/ARDS have
      revealed many molecular mechanisms that offer therapeutic opportunities for cell
      or gene therapy. Herein the present strategies and future perspectives of the
      treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell
      therapies.

PMID- 17173365
TI  - Hypertonic saline resuscitation maintains a more balanced profile of T-lymphocyte
      subpopulations in a rat model of hemorrhagic shock.
AB  - OBJECTIVE: To investigate the potential and early effect of hypertonic saline
      resuscitation on T-lymphocyte subpopulations in rats with hemorrhagic shock.
      METHODS: A model of rat with severe hemorrhagic shock was established in 18
      Sprague-Dawley (SD) rats. The rats were randomly divided into Sham group, HTS
      group (hypertonic saline resuscitation group) and NS group (normal saline
      resuscitation group). Each group contained 6 rats. The CD4(+) and CD8(+)
      subpopulations of T-lymphocytes in peripheral blood were detected respectively
      before shock and after resuscitation by double antibody labelling and flow
      cytometry. RESULTS: In the early stage after hemorrhagic shock, fluid
      resuscitation and emergency treatment, the CD4(+) lymphocytes of peripheral blood
      in HTS and NS groups markedly increased. Small volume resuscitation with HTS also
      induced peripheral CD8(+) lymphocytes to a certain extent, whereas NS
      resuscitation showed no effect in this respect. Consequently, compared with Sham
      and HTS groups, CD4(+)/CD8(+) ratio of peripheral blood in NS group was obviously
      increased, and showed statistically differences. CONCLUSION: In this model of rat
      with severe hemorrhagic shock, small volume resuscitation with HTS is more
      effective than NS in reducing immunologic disorders and promoting a more balanced
      profile of T-lymphocyte subpopulations regulating network.

PMID- 17173366
TI  - Effect of proximal femoral osteoporosis on cementless hip arthroplasty: a short
      term clinical analysis.
AB  - OBJECTIVE: The aim of this retrospective investigation was to explore the
      influence of femoral osteoporosis on short-term curative effects of cementless
      hip arthroplasty and to evaluate the femoral metaphyseal bone mineral density
      (BMD) for femoral osteoporosis in order to guide prosthesis choice and
      rehabilitation. METHODS: We performed 127 total arthroplasty operations between
      June 1999 to February 2003 and investigated 49 cementless hip replacements with
      the Metalcancellous cementless Lubeck II system being used in all hips. There
      were twenty men and twenty-nine women whose mean age at the time of the operation
      was 60 years (range, 52~81 years). The patients were divided into osteoporosis or
      normal groups according to the femoral metaphyseal BMD measured preoperatively.
      The average duration of follow-up was 30 months (range, 8~52 months). We
      evaluated all of the patients from a clinical standpoint with use of a standard
      terminology questionnaire with respect to the short-term curative effects and
      patients' satisfaction. Hip pain status and functional ability were important
      indicators of treatment efficacy. RESULTS: Harris hip score and patients'
      satisfaction in femoral osteoporosis patients who underwent noncemented hip
      arthroplasty were lower (P=0.004, P=0.03) while the incidence of thigh pain was
      higher (P=0.03) than the patients with non-osteoporosis. CONCLUSION: The higher
      incidence of pain, as well as the decrease in function experienced by the
      patients in osteoporosis group, supports the case that cementless arthroplasty is
      not a better choice for those patients and that we had better select prosthesis
      based on the femoral metaphyseal BMD.

PMID- 17173368
TI  - A regulatory perspective on issues and approaches in characterizing human
      metabolites.
AB  - This document captures the current thinking within FDA/CDER on the non-clinical
      safety assessment of human drug metabolites in new drug products. Examples are
      provided, which define a scientific based approach to the safety evaluation of
      human metabolites in new drug candidates. A discussion of the need for, and the
      adequacy of, the assessment of human drug metabolites with specific regard to
      their potential as mediators of toxicity is presented from a regulatory
      perspective.

PMID- 17173369
TI  - Safety assessment of drug metabolites: Characterization of chemically stable
      metabolites.
AB  - Drug molecules are typically subjected to a variety of biotransformation
      reactions, and the metabolites formed through these reactions must be considered
      when conducting safety testing programs for new chemical entities. Metabolites
      that are chemically stable sometimes have pharmacological activity profiles
      similar to those of the parent compound but rarely have potent activity against
      off-target receptors that is unique relative to the parent profile. This fact
      argues for the thorough testing of drug metabolites for their pharmacological
      activity. It also argues for a significantly lower need for the thorough
      characterization and quantitation of stable metabolites not thought to
      substantially contribute to the pharmacodynamic effect. Given the tremendous
      resource requirements involved in the thorough characterization of drug
      metabolites, a more flexible, tiered approach to stable metabolite
      characterization would seem to provide the best utilization of resources while
      still allowing a complete evaluation of the toxicological profile of a new drug.

PMID- 17173370
TI  - Metabolites and safety: What are the concerns, and how should we address them?
AB  - The issue of the safety of drug metabolites in humans is a complex one. In this
      commentary, a proposal is made regarding how to deal with drug metabolites
      observed in humans such that the safety of these molecules can be assured. The
      human radiolabeled ADME study, in which metabolites are identified and quantified
      in circulation and excreta, is proposed as the primary source of information on
      human metabolites from which decisions can be made regarding the need for further
      risk assessment. Although radiolabel ADME studies yield quantitative metabolite
      profiles that are commonly reported as a percentage of the total drug related
      material (for circulating metabolites) and a percentage of total dose (for
      excretory metabolites), it is essential to convert these values into absolute
      abundances. The structure of a metabolite, its abundance, the biofluid in which
      it is observed (circulation or excreta), and the toxicity mechanism of concern
      serve as the four most important characteristics for determination as to whether
      further safety consideration is warranted. Metabolites in circulation require
      consideration for toxicity that can arise by effects on specific receptors and/or
      enzymes (either target or off-target). Metabolites in excreta require
      consideration for their potential to indicate a body-burden to chemically
      reactive intermediary metabolites, which can yield toxicities of nonspecific
      mechanisms commonly associated with covalent binding (e.g., carcinogenicity,
      immunoallergic response, etc.). Through an analysis of 24 drugs removed from the
      market because of human toxicity, it was concluded that further testing of human
      metabolites would not have yielded any additional information that could have
      predicted human safety findings because human metabolites would have been present
      in the animal species routinely used in toxicology testing after the
      administration of the parent compound.

PMID- 17173372
TI  - Identification of previously unrecognized antiestrogenic chemicals using a novel
      virtual screening approach.
AB  - The physiological roles of estrogen in sexual differentiation and development,
      female and male reproductive processes, and bone health are complex and diverse.
      Numerous natural and synthetic chemical compounds, commonly known as endocrine
      disrupting chemicals (EDCs), have been shown to alter the physiological effects
      of estrogen in humans and wildlife. As such, these EDCs may cause unanticipated
      and even undesirable effects. Large-scale in vitro and in vivo screening of
      chemicals to assess their estrogenic activity would demand a prodigious
      investment of time, labor, and money and would require animal testing on an
      unprecedented scale. Approaches in silico are increasingly recognized as playing
      a vital role in screening and prioritizing chemicals to extend limited resources
      available for experimental testing. Here, we evaluated a multistep procedure that
      is suitable for in silico (virtual) screening of large chemical databases to
      identify compounds exhibiting estrogenic activity. This procedure incorporates
      Shape Signatures, a novel computational tool that rapidly compares molecules on
      the basis of similarity in shape, polarity, and other bio-relevant properties.
      Using 4-hydroxy tamoxifen (4-OH TAM) and diethylstilbestrol (DES) as input
      queries, we employed this scheme to search a sample database of approximately
      200,000 commercially available organic chemicals for matches (hits). Of the eight
      compounds identified computationally as potentially (anti)estrogenic, biological
      evaluation confirmed two as heretofore unknown estrogen antagonists. Subsequent
      radioligand binding assays confirmed that two of these three compounds exhibit
      antiestrogenic activities comparable to 4-OH TAM. Molecular modeling studies of
      these ligands docked inside the binding pocket of estrogen receptor alpha
      (ERalpha) elucidated key ligand-receptor interactions that corroborate these
      experimental findings. The present study demonstrates the utility of our
      computational scheme for this and related applications in drug discovery,
      predictive toxicology, and virtual screening.

PMID- 17173373
TI  - Involvement of semiquinone radicals in the in vitro cytotoxicity of cigarette
      mainstream smoke.
AB  - Free radicals in cigarette smoke have attracted a great deal of attention because
      they are hypothesized to be responsible in part for several of the pathologies
      related to smoking. Hydroquinone, catechol, and their methyl-substituted
      derivatives are abundant in the particulate phase of cigarette smoke, and they
      are known precursors of semiquinone radicals. In this study, the in vitro
      cytotoxicity of these dihydroxybenzenes was determined using the neutral red
      uptake (NRU) assay, and their radical-forming capacity was determined by electron
      paramagnetic resonance (EPR). All of the dihydroxybenzenes studied were found to
      generate appreciable amounts of semiquinone radicals when dissolved in the cell
      culture medium employed in the NRU assay. Hydroquinone exhibited by far the
      highest capacity to form semiquinone radicals at physiological pH, even though it
      is not the most cytotoxic dihydroxybenzene. Methyl-substituted dihydroxybenzenes
      were found to be more cytotoxic than either hydroquinone or catechol. The
      formation of semiquinone radicals via auto-oxidation of the dihydroxybenzenes was
      found to be dependent on the reduction potential of the corresponding
      quinone/semiquinone radical redox couple. The capacity to generate semiquinone
      radicals was found to be insufficient to explain the variance in the cytotoxicity
      among the dihydroxybenzenes in our study; consequently, other mechanisms of
      toxicity must also be involved. The observed interactions between 2,6
      dimethylhydroquinone and hydroquinone in the cytotoxicity assay and EPR analysis
      suggest that care needs to be taken when the bioactivity of cigarette smoke
      constituents is evaluated, i.e., the effect of the cigarette smoke complex matrix
      on the activity of the single constituent studied must be taken into
      consideration.

PMID- 17173374
TI  - Biomarkers for isocyanate exposure: Synthesis of isocyanate DNA adducts.
AB  - Isocyanates are important intermediates in industrial manufacturing. DNA adducts
      and protein adducts are important tools to biomonitor people exposed to
      xenobiotics. In the present work, the formation of DNA adducts deriving from 4
      chlorophenyl isocyanate (4CPI) and 4-methylphenyl isocyanate (4MPI) were
      explored. The adducts of 4CPI and/or 4MPI with 2'-deoxyadenosine, 2'
      deoxyguanosine, and 2'-deoxycytidine were synthesized and characterized by NMR
      and MS. For low level detection, an LC-MS/MS method was developed. The formation
      of DNA adducts was confirmed in in vitro reactions with DNA.

PMID- 17173371
TI  - Methylating agents and DNA repair responses: Methylated bases and sources of
      strand breaks.
AB  - The chemical methylating agents methylmethane sulfonate (MMS) and N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG) have been used for decades as classical DNA
      damaging agents. These agents have been utilized to uncover and explore pathways
      of DNA repair, DNA damage response, and mutagenesis. MMS and MNNG modify DNA by
      adding methyl groups to a number of nucleophilic sites on the DNA bases, although
      MNNG produces a greater percentage of O-methyl adducts. There has been
      substantial progress elucidating direct reversal proteins that remove methyl
      groups and base excision repair (BER), which removes and replaces methylated
      bases. Direct reversal proteins and BER, thus, counteract the toxic, mutagenic,
      and clastogenic effects of methylating agents. Despite recent progress, the
      complexity of DNA damage responses to methylating agents is still being
      discovered. In particular, there is growing understanding of pathways such as
      homologous recombination, lesion bypass, and mismatch repair that react when the
      response of direct reversal proteins and BER is insufficient. Furthermore, the
      importance of proper balance within the steps in BER has been uncovered with the
      knowledge that DNA structural intermediates during BER are deleterious. A number
      of issues complicate the elucidation of the downstream responses when direct
      reversal is insufficient or BER is imbalanced. These include inter-species
      differences, cell-type-specific differences within mammals and between cancer
      cell lines, and the type of methyl damage or BER intermediate encountered. MMS
      also carries a misleading reputation of being a radiomimetic, that is, capable of
      directly producing strand breaks. This review focuses on the DNA methyl damage
      caused by MMS and MNNG for each site of potential methylation to summarize what
      is known about the repair of such damage and the downstream responses and
      consequences if the damage is not repaired.

PMID- 17173376
TI  - Aerobic fate of the C-3'-thymidinyl radical in single-stranded DNA.
AB  - Oxidative events that target the sugar-phosphate backbone of DNA can lead to
      reactive fragments that interfere with DNA repair, transcription and translation
      by the formation of cross-links and adducts of proteins and nucleobases. Here we
      report the formation of several such lesions through the aerobic degradation of
      an independently generated C-3'-thymidinyl radical in 2'-deoxyoligonucleotides.
      Individual fragments were identified by independent synthesis and comparison of
      retention times in high-performance liquid chromatography (HPLC) and/or matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF
      MS) along with gel electrophoresis. The formation of this reactive intermediate
      in the presence of oxygen was found to produce 3'-phosphoglycolaldehyde (3'-PGA)
      as well as 3'-ketoenolether (3'-KEE), 3'-phosphoglycolate (3'-PG), and 5'
      aldehyde terminated oligonucleotide fragments. Additionally, a significant
      outcome of C-3'-thymidinyl radical formation in DNA oligomers is a strand break
      resulting in one 3'- and two 5'-phosphate-terminated oligomers. These results
      suggest the involvement of several sugar derived reactive species upon C-3'
      radical initiated scission of single-stranded DNA under aerobic conditions. The
      electrophilic nature of several of these products as well as their formation
      through a single oxidative event can make the presence of a C-3'-DNA radical more
      detrimental to the cell than products derived from more frequently occurring DNA
      sugar radicals.

PMID- 17173375
TI  - Arsenic disruption of steroid receptor gene activation: Complex dose-response
      effects are shared by several steroid receptors.
AB  - Chronic intake of arsenic (As) has been associated with increased risk of cancer,
      diabetes, developmental and reproductive problems, and cardiovascular disease.
      Recent studies suggest increased health risks with drinking water levels as low
      as 5-10 ppb. We previously reported that As disrupts glucocorticoid receptor (GR)
      mediated transcription in a very complex fashion. Low As levels (0.1-0.7 microM)
      stimulated transcription, whereas slightly higher levels (1-3 microM) were
      inhibitory. The DNA binding domain (DBD) was the minimal region of GR required
      for the response to As. Mutations in the DBD that alter the conformation of the
      dimerization domain (D-loop) to a DNA-bound GR conformation abolished the
      stimulatory effect and enhanced the inhibitory response to As. Here we report
      that receptors for progesterone (PR) and mineralocorticoids display a complex As
      response similar to that of the GR, suggesting a common mechanism for this
      effect. The complex response to As is not due to altered steroid or receptor
      levels. Moreover, a well-characterized GR dimerization mutant displayed a wild
      type biphasic response to As for several divergent reporter genes, suggesting
      that dimerization is not critical for the response to As. Fluorescence
      polarization studies with purified PR and GR demonstrated that the specific PR/GR
      DNA interaction is not altered in the presence of As. These results indicate that
      the numerous and diverse human health effects associated with As exposure may be
      mediated, at least in part, through its ability to simultaneously disrupt
      multiple hormone receptor systems.

PMID- 17173377
TI  - Citrate does not change uranium chemical speciation in cell culture medium but
      increases its toxicity and accumulation in NRK-52E cells.
AB  - Uranium (U), as a heavy metal, is a strong chemical toxicant, which induces the
      damage to proximal tubule kidney cells. In order to reproduce U toxicity in vitro
      and to avoid precipitation, it is necessary to complex it with a strong ligand
      such as bicarbonate before dilution with cell culture medium. It was recently
      shown, in vitro on the NRK-52E normal renal tubular epithelial cells, that
      citrate increased the toxicity of U(VI)-bicarbonate complexes. This property was
      attributed to a change in U speciation, characterized by the occurrence of U(VI)
      citrate complexes, which were supposed to be more toxic than U(VI)-bicarbonate.
      Here, we present the results of extended X-ray absorption fine structure
      spectroscopy (EXAFS) analyses of the media that were used to expose cells in
      vitro. Resulting data show that even when citrate is added to the exposure
      medium, the predominant species is U(VI)-bicarbonate. Nonetheless, citrate
      increases U(VI) toxicity and accelerates its intracellular accumulation kinetics,
      without inducing precipitation. This study emphasizes another parameter that
      modulates U(VI) toxicity for renal tubule cells and further characterizes the
      mechanisms of U(VI) toxicity.

PMID- 17173378
TI  - Oxidative metabolism of seleno-L-methionine to L-methionine selenoxide by flavin
      containing monooxygenases.
AB  - The roles of flavin-containing monooxygenases (FMOs) in the oxidation of seleno-l
      methionine (SeMet) to l-methionine selenoxide (MetSeO) were investigated using
      cDNA-expressed human FMOs, purified rat liver FMOs, and rat liver microsomes.
      MetSeO and the N-2,4-dinitrophenyl-derivatives of SeMet and MetSeO were
      synthesized and characterized by 1H-NMR and ESI/MS. These reference compounds
      were then used to develop a sensitive HPLC assay to monitor SeMet oxidation to
      MetSeO. The formation of MetSeO in rat liver microsomes was time-, protein
      concentration-, SeMet concentration-, and NADPH-dependent. The microsomal
      activity exhibited a SeMet Km value (mean +/- S.D.; n = 4) of 0.91 +/- 0.29 mM
      and a Vmax value of 44 +/- 8.0 nmol MetSeO/mg protein/min. The inclusion of 1
      benzylimidazole, superoxide dismutase, or deferoxamine caused no inhibition of
      the rat liver microsomal activity. Because these results suggested the
      involvement of FMOs in the oxidation of SeMet in rat liver microsomes, the
      formation of MetSeO was also examined using cDNA-expressed human and purified rat
      FMOs. The results showed that both rat and human FMO1 and FMO3 but not FMO5 can
      catalyze the reaction. The SeMet kinetic constants were obtained with purified
      rat liver FMO3 (Km = 0.11 mM, Vmax = 280 nmol/mg protein/min) and rat liver FMO1
      (Km = 7.8 mM, Vmax = 1200 nmol/mg protein/min). Because SeMet has anti-cancer,
      chemopreventive, and toxic properties, the kinetic results suggest that FMO3 is
      likely to play a role in the biological activities of SeMet at low exposure
      conditions.

PMID- 17173379
TI  - Inhibition of cytochrome P450 3A4 by a pyrimidineimidazole: Evidence for complex
      heme interactions.
AB  - PH-302 inhibits the inducible form of nitric oxide synthase (iNOS) by
      coordinating with the heme of the monomeric form and preventing formation of the
      active dimer. Inherent with the mechanism of pharmacology for this compound was
      the inhibition of cytochrome P450 3A4 (P450 3A4), observed from early ADME
      screening. Further investigation showed that PH-302 inhibited P450 3A4
      competitively with a Ki of approximately 2.0 microM against both midazolam and
      testosterone hydroxylation in human liver microsomes. As expected, spectral
      binding analysis demonstrated that inhibition was a result of type II
      coordination to the P450 heme with the imidazole moiety of PH-302, although only
      72% of the maximal absorbance difference was achievable with PH-302 compared to
      that of the smaller ligand imidazole. Time-dependent inhibition of P450 3A4 by PH
      302 was also observed because of metabolite-inhibitory (MI) complex formation via
      metabolism of the methylenedioxyphenyl group. The profile for time-dependent
      inhibition in recombinant P450 3A4 was biphasic, and was kinetically
      characterized by a kinact of 0.08 min-1 and a Ki of 1.2 microM for the first
      phase (0-1.5 min) and a kinact of 0.06 min-1 and a Ki of 23.8 microM for the
      second phase (1.5-10 min). Spectral characterization of the PH-302 MI complex
      demonstrated that formation began to plateau within 3 min, consistent with the
      kinetic profile of inactivation by PH-302. Meanwhile, spectral evidence for the
      imidazole-derived type II difference spectrum of PH-302 was captured
      simultaneously with the formation of the MI complex. The presence of
      simultaneously operable type II coordination and rapidly saturable MI complex
      formation with heme by PH-302 indicates the presence of complex heme interactions
      with this unique molecule. Information from these mechanistic studies adds to our
      understanding of the nature of P450 3A4 inhibition by PH-302 and provides a
      potentially useful tool compound for future studies investigating binding
      interactions in this important drug-metabolizing enzyme.

PMID- 17173380
TI  - Dihydroxy-, hydroxyspirolactone-, and dihydroxyspirolactone-urochlorins induced
      by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the liver of mice.
AB  - Previous work has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes
      porphyria, enhanced by iron, in C57BL/6J mice with marked accumulation in the
      liver of uroporphyrin I and III isomers and heptacarboxylic acid III and is one
      model of human porphyria cutanea tarda. Preliminary examination by HPLC also
      indicated the presence of some oxygenated side chain uroporphyrin derivatives.
      Here, the porphyrin constituents of TCDD-induced porphyric liver have been
      examined by HPLC/electrospray ionization quadrupole time-of-flight mass
      spectrometry (HPLC/ESI-Q-TOFMS) to characterize the major and minor porphyrins
      present in hepatic tissue. As well as the major constituents uroporphyrins I and
      III, we identified the isomers of heptacarboxylic, hexacarboxylic, and
      pentacarboxylic acid porphyrins arising from intermediates in the stepwise
      decarboxylation of uroporphyrinogen I and III to coproporphyrinogens. In
      addition, monohydroxy analogues of uroporphyrin isomers were detected
      hydroxylated in the acetic acid and beta-positions of propionic acid side chains
      and in the meso ring position. Of particular note, for the first time for human
      and experimental porphyrias, we found chlorins (dihydroxy-, hydroxyspirolactone-
      ,and dihydroxyspirolactone-urochlorins) consistent with those derived from an
      epoxyurochlorin structure, formed by oxidation of the double bond of a pyrrole
      ring of uroporphyrinogen I and III isomers. The findings demonstrate that oxygen
      insertion into the pyrrole rings of uroporphyrinogens occurs under pathological
      circumstances in vivo and support the evidence for an oxidative cellular
      environment present in TCDD-treated porphyric tissue.

PMID- 17173381
TI  - Protein and low molecular mass thiols as targets and inhibitors of glycation
      reactions.
AB  - Protein glycation has been implicated in the aging process as well as the
      complications of diabetes (retinopathy, neuropathy, nephropathy, and
      atherosclerosis). The nitrogen substituents of Lys, Arg, and His residues and the
      N-terminus of proteins are known to be readily glycated. As the thiol group of
      Cys is a powerful nucleophile, we hypothesized that Cys residues should also be
      targets of glycation and that low molecular mass thiols may act as protective
      agents. In this study the role of thiol glycation, induced by dicarbonyls, in
      protein cross-link formation and damage prevention is examined. It is shown that
      incubation of creatine kinase with glyoxal results in protein cross-link
      formation, with this occurring concurrently with loss of thiol groups, enzyme
      inactivation, and formation of S-carboxymethylcysteine, a product of glyoxal
      adduction to Cys residues. Cross-links have also been detected between N
      acetylcysteine and the Lys-rich protein histone H1, demonstrating the formation
      of thiol-glyoxal-amine cross-links. Mass spectrometry has been used to
      characterize some of these cross-links as 2-(alkylthio)acetamides. A range of low
      molecular mass thiols have been shown to inhibit dicarbonyl adduction to, and
      cross-linking of, the thiol-free protein lysozyme, consistent with these thiols
      being alternative (sacrificial) targets of glycation. Some of these thiols are
      more efficient modulators of glycation than established glycation inhibitors such
      as aminoguanidine. These data demonstrate that thiols are facile targets of
      glycation and that low molecular mass thiols are potent glycation inhibitors.
      These data may aid the design of therapeutic agents for the treatment of the
      complications of diabetes.

PMID- 17173384
TI  - Three-dimensional heterometallic chiral Cr-Mn compound constructed by cyanide and
      dicyanamide bridges.
AB  - Increasing the number of chiral centers by adjusting auxiliary coligands results
      in a heterometallic metamagnet with a three-dimensional homochiral framework
      containing both cyanide and dicyanamide bridges.

PMID- 17173385
TI  - A supercooled imidazolium iodide ionic liquid as a low-viscosity electrolyte for
      dye-sensitized solar cells.
AB  - A series of allyl-functionalized imidazolium salts are reported, including 1
      allyl-3-ethylimidazolium iodide and 1-allyl-3-propylimidazolium iodide, which
      have melting points close to room temperature and show typical properties of
      supercooled fluids if heated above their melting points. Their viscosities in the
      liquid state are considerably lower than the benchmark ionic liquid used in solar
      cells, viz., 1-propyl-3-methylimidazolium iodide. Electrolytes containing these
      new liquids provide excellent efficiencies and good stability in dye-sensitized
      solar cells when subjected to an accelerated-light soaking test at 60 degrees C.
      The structures of three of the new salts have been established in the solid state
      by single-crystal X-ray analysis.

PMID- 17173386
TI  - Sodium zinc hydroxide sulfite with a novel Zn3OH geometry.
AB  - The synthesis and crystal structure of a new sodium zinc hydroxide sulfite,
      Na[(Zn(OH)]3(SO3)2, with novel structural features and bonding geometry are
      reported. In Na[(Zn(OH)]3(SO3)2, Zn2+ and O2- alternate to form an interesting
      corrugated hexagonal sheet with rings consisting of (ZnO)3. Another rare
      occurrence is the bonding geometry of one-third of the O sites within the sheet.
      These O sites form a planar Zn3O unit, unlike other known compounds, in which
      Zn3O is pyramidal.

PMID- 17173387
TI  - A multifunctional tetrametallic Ru-Pt supramolecular complex exhibiting both DNA
      binding and photocleavage.
AB  - A new tetrametallic supramolecular complex, [{(bpy)2Ru(dpp)}2Ru(dpp)PtCl2](PF6)6
      (bpy = 2,2'-bipyridine, dpp = 2,3-bis(2-pyridyl)pyrazine), has been prepared and
      characterized. This supramolecular assembly is multifunctional, forming
      coordinate covalent bonds to DNA through its cis-PtCl2 moiety and photocleaving
      DNA through its Ru polypyridine chromophores. Electronic absorption spectroscopy
      shows ligand-based pi-->pi* transitions in the UV with Ru-based metal-to-ligand
      charge transfer transitions throughout much of the visible. The Ru-->dpp CT
      transitions center at 542 nm (eta = 35 000 M-1 cm-1). This complex has a HOMO
      localized on peripheral Ru with E(1/2)oxd = 1.58 V vs Ag/AgCl, and a LUMO based
      on the mu-dpp connecting Ru and Pt, E(1/2)red = -0.40 V. Gel electrophoresis
      analysis shows the tetrametallic coordinates to pUC18 DNA and, when excited with
      visible light, cleaves DNA through an oxygen-mediated pathway.

PMID- 17173388
TI  - Visible-light-sensitized near-infrared luminescence from rare-earth complexes of
      the 9-hydroxyphenalen-1-one ligand.
AB  - The unique absorption properties of the 9-hydroxyphenalen-1-one (HPHN) ligand
      have been exploited to obtain visible-light-sensitizable rare-earth complexes in
      1:3 and 1:4 metal-to-ligand ratios. In both stoichiometries (1:3, tris, Ln(PHN)3;
      1:4, tetrakis, A[Ln(PHN)4], with Ln being a trivalent rare-earth ion and A being
      a monovalent cation), the complexes of Nd(III), Er(III), and Yb(III) show typical
      near-infrared luminescence upon excitation with visible light with wavelengths up
      to 475 nm. The X-ray crystal structures of the tris complexes show solvent
      coordination to the central rare-earth ion, whereas in the tetrakis complexes,
      the four PHN- ligands form a protective shield around the central ion, preventing
      small solvent molecules from coordinating to the rare-earth ion, at least in the
      solid state.

PMID- 17173389
TI  - Uranyl complexation by chloride ions. Formation of a tetrachlorouranium(VI)
      complex in room temperature ionic liquids [Bmim][Tf2N] and [MeBu3N][Tf2N].
AB  - The tetrachlorouranium(VI) complex is formed in [Bmim][Tf2N] and [MeBu3N][Tf2N]
      from a uranium(VI) solution in the presence of a stoichiometric quantity of
      chloride ions. The [UVIO2Cl4]2- absorption and emission spectra show bands
      splitting in comparison with the [UVIO2]2+ spectra, as observed in the solid
      state, organic solvents, and chloroaluminate-based ionic liquids. The
      fluorescence lifetime of [UO2Cl4]2- in [MeBu3N][Tf2N] is 0.7 +/- 0.1 mus. The
      reduction potential of this complex is -1.44 and -1.8 V vs Ag/Ag+ respectively in
      [Bmim][Tf2N] and [MeBu3N][Tf2N] and does not depend on the chloride
      concentration. The mechanism proposed for the redox process is a monoelectronic
      reduction to form [UVO2Cl4]3-, followed by a chemical reaction. The
      tetrachlorouranium(V) complex seems more stable in [Bmim][Tf2N] than in
      [MeBu3N][Tf2N]. The electrochemical analysis put in evidence specific
      interactions of the ionic liquid cation with the uranium anionic species.

PMID- 17173390
TI  - A novel hexatungstate fragment stabilized by dimethyltin groups:
      [{(CH3)2Sn}2(W6O22)]4-.
AB  - Reaction of Na2WO4 and (CH3)2SnCl2 in water (pH 7) led to the formation of the
      hybrid organic-inorganic polyanion [{(CH3)2Sn}2(W6O22)]4- (1), which is composed
      of a novel hexatungstate core stabilized by two dimethyltin groups. Selective
      crystallization of 1 with guanidinium cations resulted in
      [C(NH2)3]4[{CH3)2Sn}2(W6O22)]2H2O (1a), which exhibits a 1D arrangement via
      distorted trigonal-bipyramidal cis-(CH3)2SnO3 moieties.

PMID- 17173391
TI  - [Ln2(C2O4)2(pyzc)2(H2O)2]n[Ln = Pr (1), Er (2)]: novel two-dimensional lanthanide
      coordination polymers with 2-pyrazinecarboxylate and oxalate.
AB  - We report for the first time hydrothermal synthesis of lanthanide-pyzcH polymers,
      [Ln2(C2O4)2(pyzc)2 (H2O)2]n [Ln = Pr (1), Er (2)], in which pyzcH was decomposed
      into C2O42- and thus caused novel two-dimensional hexagonal lattice networks. The
      magnetic property of polymer 1 has been studied by an approximate treatment being
      enlightened by McPherson et al. (Inorg. Chim. Acta 1988, 148, 265), leading to
      Delta = -4.3 cm-1, zJ' = -11.73 cm-1, and g = 0.79. Complex 2 displays an intense
      room-temperature, liquid-state luminescent emission.

PMID- 17173392
TI  - Unprecedented formation of a rhodium cluster triggered by rhodium-fastened N
      confused gable porphyrin.
AB  - Thermal reaction of N-confused porphyrin (NCP) with [RhCl(CO)2]2 caused
      unprecedented formation of tetranuclear rhodium complex Rh4(NCP)2(CO)4 having a
      gable-porphyrin-type structure, where two porphyrin pi systems were
      electronically connected by the rhodium cluster.

PMID- 17173393
TI  - A singular noninterpenetrating coordination polymer with the Pt3O4 structure
      containing naked [Na+]4 units.
AB  - The homoleptic low-spin complex [Fe(L)3]2+ where L is the bisbidentate ligand
      1,10-phenanthroline-5,6-dione, coordinates Na+ ions via exo-oriented dione groups
      defining a three-dimensional cationic network {[Fe(L)3]4Na3}11+}n with Pt3O4
      topology. The large volume generated by the network is filled with 11 perchlorate
      ions, 7 "NaClO4" ionic pairs, and 9 H2O molecules. Singular [Na+]4 units, in
      which the Na+ ions are practically uncoordinated, are formed.

PMID- 17173394
TI  - Dancing of palladacycles around a "juggler" 2,2-diacetyl-1,1-ethylenedithiolato
      ligand in a trinuclear Pd(II) complex.
AB  - A trinuclear Pd complex containing a mu3-1,1-ethylenedithiolato ligand has been
      synthesized and its structure confirmed by X-ray crystallography. It is the first
      example of a 1,1-ethylenedithiolato complex containing an anionic carbon sigma
      donor. This compound shows an unprecedented fluxional behavior in solution, by
      which the three palladacycles exchange around the dithiolene. The activation
      parameters for this process have been derived by NMR line shape analysis, and a
      mechanism is proposed.

PMID- 17173395
TI  - Layered heterometallic iodoplumbate containing a novel Pb3Cu6I16 net: structure
      and optical properties.
AB  - A new heterometallic iodoplumbate was synthesized solvothermally. The complex,
      [Co(phen)3][Pb3Cu6I16].C2H5OH, contains a novel Pb3Cu6I16 net made up of linked
      Pb3I11 and Cu6I11 clusters. The clusters form a BN-type layer, where the Pb3I11
      and Cu6I11 clusters take the place of B and N. The layers, which are separated by
      [Co(phen)3]2+ cations, contain cavities in which ethanol molecules are located.

PMID- 17173396
TI  - Co(II)-Co(II) paddlewheel complex with a redox-active ligand derived from TTF.
AB  - A new trimethyltetrathiafulvalene (Me3TTF) derivative Me3TTF-CH=CH-py bearing a
      pyridyl was synthesized and coordinated to a cobalt(II) benzoate dimer, having
      paddlewheel core structure, leading to a complex formulated as Co2(PhCOO)4(Me3TTF
      CH=CH-py)2. Single-crystal X-ray diffraction studies of the complex performed at
      293 and 100 K evidenced the existence of a weak metal-metal interaction. Magnetic
      studies revealed an antiferromagnetic behavior, which is explained as the result
      of the direct exchange between metal centers.

PMID- 17173397
TI  - A new hexaferrocene complex with a [M3(mu3-O)]7+ core.
AB  - The new hexaferrocene complex 1 has been synthesized and characterized by X-ray
      diffraction. Its magnetization data were fitted to a detailed theoretical model
      that considers nonequivalent exchange parameters between Fe ions to yield the
      magnetic exchange coupling values of J1/kB = -31.5 K and J2/kB = -25.8 K.
      Moreover, the cyclic voltammogram of complex 1 confirmed its redox activity
      associated with the presence of ferrocene units, with very small or negligible
      electronic interactions between them.

PMID- 17173399
TI  - Suzuki coupling at the periphery of diruthenium coordination and organometallic
      compounds.
AB  - A series of diruthenium compounds, Ru2(DArF)3(L")Cl (2), where the auxiliary
      ligand DArF is DmAniF or D(3,5-Cl2Ph)F and L" is one of the diarylformamidinate
      ligands containing at least one biphenyl, were prepared from Suzuki reactions
      between Ru2(DArF)3(L')Cl (1), where L' is (4-I-Ph)NC(H)NPh (N-(4-iodophenyl)-N'
      phenylformamidinate) or D(4-I-Ph)F (N,N'-di(4-iodophenyl)formamidinate), and
      ArB(OH)2 (Ar = Ph and 4-CH3C(O)Ph) in satisfactory yields. Alkynylation of the
      type 2 compounds with LiCCPh yielded the alkynyl derivatives Ru2(DArF)3(L")(CCPh)
      (3). Alternatively, type 3 compounds can be prepared from the Suzuki coupling
      reaction between Ru2(DArF)3(L')(C2Ph) and ArB(OH)2. A structural comparison
      between the type 1 and 2 compounds revealed minimal changes in the coordination
      sphere of Ru2 core. Cyclic voltammograms of Suzuki derivatives resemble those of
      the parent compounds, indicating the retention of the electrophore characteristic
      of diruthenium species upon peripheral modification.

PMID- 17173398
TI  - Phosphazene cations.
AB  - Cations derived from (NPCl2)3, hexachloro-cyclo-triphosphazene, the weakly basic
      precursor of phosphazene polymers, have been prepared using strongly
      electrophilic reagents based on carborane anions. N-protonated, N-methylated, and
      N-silylated adducts of (NPCl2)3 have been isolated and characterized by X-ray
      crystallographic and spectroscopic methods. The normally potent chloride
      abstracting silyl reagents of the type R3Si(carborane) are unable to abstract
      chloride from (NPCl2)3, even though the coordinatively unsaturated N2P2Cl5+
      cation is widely accepted as a reactive intermediate in the ring-opening
      polymerization of (NPCl2)3.

PMID- 17173400
TI  - Synthesis of isostructural cage complexes of copper with cobalt and nickel for
      deposition of mixed ceramic oxide materials.
AB  - Heterobimetallic molecular precursors [Co2(acac)2mu-OH)2Cu4(dmae)4Cl4] (2) and
      [Ni2(acac)2(mu-OH)2Cu4(dmae)4Cl4] (3) [dmaeH = N,N-dimethylaminoethanol and acac
      = 2,4-pentanedionate] for the deposition of mixed oxide thin films were prepared
      by the interaction of tetrameric N,N-dimethylaminoethanolato copper(II) chloride,
      [Cu(dmae)Cl]4 (1) with M(acac)2.xH2O, [M = Co, Ni] in toluene. Both
      heterobimetallic cage complexes were characterized by melting point, elemental
      analysis, FT-IR spectroscopy, mass spectrometry, magnetometery, and single
      crystal X-ray diffraction. Complexes 2 and 3 are isostructural and crystallize in
      the monoclinic space group P21/n. A TGA study shows that both complexes undergo
      controlled thermal decomposition at 450 degrees C to give mixed metal oxides.
      Solid-state infrared spectroscopy (FT-IR), scanning electron microscopy (SEM),
      energy-dispersive X-ray analysis (EDX), and X-ray powder diffraction (XRD)
      analysis were performed to analyze the chemical composition and surface
      morphology of the deposited oxide thin films. The results obtained indicate the
      formation of impurity-free crystalline mixed oxide films with particle sizes
      ranging from 0.55 to 2.0 microm.

PMID- 17173401
TI  - Direct electrical measurement of the conversion of metal acetates to metal
      sulfides by hydrogen sulfide.
AB  - Copper acetate and related metal salt films react directly with hydrogen sulfide
      at room temperature to form metal sulfides, resulting in conductivity changes as
      large as 108. The observed changes in conductivity are related to the solubility
      product constant (Ksp) and the difference in conductivity between the metal salt
      and the resulting metal sulfide. A smaller Ksp indicates a more stable metal
      sulfide and, therefore, greater metal salt reactivity. Polyaniline
      nanofiber/metal salt composites were also examined and show metal sulfide
      conversion with changes in resistance up to 106. The direct electrical
      measurement of the conversion of metal salt to metal sulfide has the potential to
      be the basis of a new type of sensitive, thin-film chemical sensor.

PMID- 17173402
TI  - Potassium Phthalocyanine, KPc: one-dimensional molecular stacks bridged by K+
      ions.
AB  - We report the synthesis of potassium phthalocyanine (KPc) and its structural
      characterization by synchrotron X-ray powder diffraction. We find that while KPc
      adopts the beta-polymorphic structural type (monoclinic space group P21/a) common
      for many MPc solids, its structure is characterized by unique features. The K+
      ions, which are statistically disordered over two symmetry-equivalent positions,
      reside in the intrastack spacing of the rodlike molecular assemblies and strongly
      bond equidistantly to selected N atoms of the two neighboring Pc rings along the
      chain direction with an unusual 5-fold coordination. The K+-stuffed slipped
      stacks of Pc units display much greater intrastack and slippage distances than
      those of other beta-MPc polymorphs. They may be thought as comprising disordered
      dimeric (Pc)22- units; this leads to electron pairing and is consistent with the
      observed nonmagnetic response of the system.

PMID- 17173403
TI  - Structural, spectroscopic, and magnetic study of bis(9,10-dihydro-9-oxo-10
      acridineacetate)bis(imidazole)bis(methanol) nickel(II).
AB  - The mixed ligand complex [Ni(CMA)2(im)2(MeOH)2] (where CMA = 9,10-dihydro-9-oxo
      10-acridineacetate ion, im = imidazole) was prepared, and its crystal and
      molecular structure were determined. The nickel ions are hexa-coordinated by four
      oxygen atoms of the carboxylate and hydroxyl groups and by two imidazole nitrogen
      atoms, to form a distorted octahedral arrangement. The structure consists of a
      one-dimensional network of the complex molecules connected by strong
      intermolecular hydrogen bonds. The weak intermolecular C-H...X hydrogen bonds and
      stacking interactions make up the 2-D structure. Very strong intramolecular
      hydrogen bonds significantly affect the geometry and vibrational characteristics
      of the carboxylate group. The UV-vis-NIR electronic spectrum was deconvoluted
      into Gaussian components. Electronic bands of the Ni(II) ion were assigned to
      suitable spin-allowed transitions in the D4h symmetry environment. The single ion
      zero-field splitting (ZFS) parameters for the S = 1 state of Ni(II), as well as
      the g components, have been determined by high-field and high-frequency EPR (HF
      HFEPR) spectroscopy over the frequency range of 52-432 GHz and with the magnetic
      fields up to 14.5 T: D = 5.77(1) cm-1, E = 1.636(2) cm-1, gx = 2.29(1), gy =
      2.18(1), and gz = 2.13(1). These values allowed us to simulate the powder
      magnetic susceptibility and field-dependent magnetization of the complex.

PMID- 17173404
TI  - Mo(W)/Cu/S cluster-based supramolecular arrays assembled from preformed clusters
      [Et4N]4[WS4Cu4I6] and [(n-Bu)4N]2[MoOS3Cu3X3] (X = I, SCN) with flexible ditopic
      ligands.
AB  - In our working toward the rational design and synthesis of cluster-based
      supramolecular architectures, a set of new [WS4Cu4]- or [MoOS3Cu3]-based
      supramolecular assemblies have been prepared from reactions of preformed cluster
      compounds [Et4N]4[WS4Cu4I6] (1) and [(n-Bu)4N]2[MoOS3Cu3X3] (2, X = I; 3, X =
      SCN) with flexible ditopic ligands such as dipyridylsulfide (dps), dipyridyl
      disulfide (dpds), and their combinations with dicyanamide (dca) anion and 4,4'
      bipy. The cluster precursor 1 reacted with dps or dpds and sodium dicyanamide
      (dca) in MeCN to produce [WS4Cu4I2(dps)3].2MeCN (4.2MeCN) and
      [WS4Cu4(dca)2(dpds)2].Et2O.2MeCN (5.Et2O.2MeCN), respectively. On the other hand,
      treatment of 2 with dpds in DMF/MeCN afforded
      [MoOS3Cu3I(dpds)2].0.5DMF.2(MeCN)0.5 (6.0.5DMF.2(MeCN)0.5) while reaction of 3
      with sodium dicyanamide (dca) and 4,4'-bipy in DMF/MeCN gave rise to
      [MoOS3Cu3(dca)(4,4'-bipy)1.5].DMF.MeCN (7.DMF.MeCN). Compounds 4.2MeCN,
      5.Et2O.2MeCN, 6.0.5DMF.2(MeCN)0.5, and 7.DMF.MeCN have been characterized by
      elemental analysis, IR spectroscopy, and single-crystal X-ray crystallography.
      Compound 4 contains a 2D layer array made of the saddle-shaped [WS4Cu4] cores
      interlinked by three pairs of Cu-dps-Cu bridges. Compound 5 has another 2D layer
      structure in which the [WS4Cu4] cores are held together by four pairs of Cu-dca
      Cu and Cu-dpds-Cu bridges. Compound 6 displays a 1D spiral chain structure built
      of the nido-like [MoOS3Cu3] cores via two pairs of Cu-dpds-Cu bridges. Compound 7
      consists of a 2D staircase network in which each [MoOS3Cu3(4,4'-bipy]2 dimeric
      unit interconnects with four other equivalent units by a pair of 4,4'-bipy
      ligands and two pairs of dca anions. The [WS4Cu4] core in 4 or 5 and the
      [MoS3Cu3] core in 7 show a planar 4-connecting node and a seesaw-shaped 4
      connecting node, respectively, which are unprecedented in cluster-based
      supramolecular compounds. The successful assembly of 4-7 from the three cluster
      precursors 1-3 through flexible ditopic ligands provides new routes to the
      rational design and construction of complicated cluster-based supramolecular
      arrays.

PMID- 17173405
TI  - Where is the limit of highly fluorinated high-oxidation-state osmium species?
AB  - The structures and stabilities of various osmium fluorides and oxyfluorides in
      high oxidation states have been studied by quantum-chemical calculations at DFT
      (B3LYP), MP2, CCSD, and CCSD(T) levels. The calculations indicate that the
      homoleptic fluorides all the way up to OsF8 may exist, even though OsF8 will be
      difficult to prepare. The last missing osmium oxyfluoride, OsOF6, is computed to
      be thermochemically stable against mononuclear gas-phase elimination reactions.
      The problem with the nonexistence of such highly fluorinated complexes appears
      thus to be mainly in difficult synthetic access under typical condensed-phase
      conditions. Matrix-isolation techniques might provide a means to characterize the
      highly fluorinated OsVIII and OsVII species.

PMID- 17173406
TI  - Superstructure in RE2-xFe4Si14-y (RE = Y, Gd-Lu) characterized by diffraction,
      electron microscopy, and Mossbauer spectroscopy.
AB  - Ternary rare-earth iron silicides RE(2-x)Fe4Si(14-y) (RE = Y, Gd-Lu; x
      approximately equal to 0.8; y approximately equal to 4.1) crystallize in the
      hexagonal system with a approximately equal to 3.9 A, c approximately equal to
      15.3 A, Pearson symbol hP20-4.9. Their structures involve rare-earth silicide
      planes with approximate compositions of "RE1.2Si1.9" alternating with beta-FeSi2
      derived slabs and are part of a growing class of rare-earth/transition-metal/main
      group compounds based on rare-earth/main-group element planes interspersed with
      (distorted) fluorite-type transition-metal/main-group element layers. The rare
      earth silicide planes in the crystallographic unit cells show partial occupancies
      of both the RE and Si sites because of interatomic distance constraints.
      Transmission electron microscopy reveals a 4a x 4b x c superstructure for these
      compounds, whereas further X-ray diffraction experiments suggest ordering within
      the ab planes but disordered stacking along the c direction. A 4a x 4b structural
      model for the rare-earth silicide plane is proposed, which provides good
      agreement with the electron microscopy results and creates two distinct Fe
      environments in a 15:1 ratio. Fe-57 Mossbauer spectra confirm these two different
      iron environments in the powder samples. Magnetic susceptibilities suggest weak
      (essentially no) magnetic coupling between rare-earth elements, and resistivity
      measurements indicate poor metallic behavior with a large residual resistivity at
      low temperatures, which is consistent with disorder. First-principles electronic
      structure calculations on model structures identify a pseudogap in the densities
      of states for specific valence-electron counts that provides a basis for a useful
      electron-counting scheme for this class of rare-earth/transition-metal/main-group
      compounds.

PMID- 17173407
TI  - New Ru complexes containing the N-tridentate bpea and phosphine ligands:
      consequences of meridional vs facial geometry.
AB  - The synthesis and isolation of the complex cis,fac-[RuIICl2(bpea)(PPh3)][3; bpea
      = N,N-bis(2-pyridylmethyl)ethylamine] and three geometrical isomers of the
      complex [RuIICl(bpea)(dppe)](BF4) [4; dppe = (1,2-diphenylphosphino)ethane],
      trans,fac (4a), cis,fac (4b), and mer(down) (4c), have been described (see Chart
      1 for a drawing of their structures). These complexes have been characterized
      through analytical, spectroscopic (IR, UV/vis, and 1D and 2D NMR), and
      electrochemical (cyclic voltammetry) techniques. In addition, complexes 3, 4a,
      and 4b have been further characterized in the solid state through monocrystal X
      ray diffraction analysis. The molecular and electronic structures of isomers 4a,
      4b, 4c, and 4d (the mer(up) isomer) have also been studied by means of density
      functional theory (DFT) calculations. Furthermore, their low-energy electronic
      transitions have been simulated using time-dependent DFT approaches, which have
      allowed unraveling of their metal-to-ligand charge-transfer nature. Complexes 3
      and 4a-c are capable of catalyzing H-transfer types of reactions between alcohols
      and aromatic ketones such as acetophenone and 2,2-dimethylpropiophenone (DP). A
      strong influence of the facial versus meridional geometry in the bpea ligand
      coordination mode is observed for these catalytic reactions, with the meridional
      isomer being much more active than the facial one. The meridional isomer is even
      capable of carrying out the H-transfer reaction of bulky substrates such as DP at
      room temperature.

PMID- 17173409
TI  - Structural and magnetic diversity in cyano-bridged bi- and trimetallic complexes
      assembled from cyanometalates and [M(rac-CTH)]n+ building blocks (CTH = d,l
      5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane).
AB  - Seven new cyano-bridged heterometallic systems have been prepared by assembling
      [M'(rac-CTH)]n+ complexes (M' = CrIII, NiII, CuII), which have two cis available
      coordination positions, and [M(CN)6]3- (M = FeIII, CrIII) and [Fe(CN)2(bpy)2]+
      cyanometalate building blocks. The assembled systems, which have been
      characterized by X-ray crystallography and magnetic investigations, are the
      molecular squares (meso-CTH-H2)[{Ni(rac-CTH)}2{Fe(CN)6)}2].5H2O (2) and [{Ni(rac
      CTH)}2{Fe(CN)2(bpy)2}2](ClO4)4.H2O (5), the bimetallic chain [{Ni(rac
      CTH)}2{Cr(CN)6)}2Ni(meso-CTH)].4H2O (3), the trimetallic chain [{Ni(rac
      CTH)}2{Fe(CN)6)}2Cu(cyclam)]6H2O (4), the pentanuclear complexes [{Cu(rac
      CTH}3{Fe(CN)6}2].2H2O (6) and [{Cu(rac-CTH)}3{Cr(CN)6)}2].2H2O (7), and the
      dinuclear complex [Cr(rac-CTH)(H2O)Fe(CN)6].2H2O (8). With the exception of 5,
      all compounds exhibit ferromagnetic interaction between the metal ions (JFeNi =
      12.8(2) cm-1 for 2; J1FeCu= 13.8(2) cm-1 and J2FeCu= 3.9(4) cm-1 for 6; J1CrCu=
      6.95(3) cm-1 and J2CrCu= 1.9(2)cm-1 for 7; JCrFe = 28.87(3) cm-1 for 8). Compound
      5 exhibits the end of a transition from the high-spin to the low-spin state of
      the octahedral FeII ions. The bimetallic chain 3 behaves as a metamagnet with a
      critical field Hc = 300 G, which is associated with the occurrence of week
      antiferromagnetic interactions between the chains. Although the trimetallic chain
      4 shows some degree of spin correlation along the chain, magnetic ordering does
      not occur. The sign and magnitude of the magnetic exchange interaction between
      CrIII and FeIII in compound 8 have been justified by DFT type calculations.

PMID- 17173408
TI  - Crystal structure and peroxidase activity of myoglobin reconstituted with iron
      porphycene.
AB  - The incorporation of an artificially created metal complex into an apomyoglobin
      is one of the attractive methods in a series of hemoprotein modifications. Single
      crystals of sperm whale myoglobin reconstituted with 13,16-dicarboxyethyl-2,7
      diethyl-3,6,12,17-tetramethylporphycenatoiron(III) were obtained in the imidazole
      buffer, and the 3D structure with a 2.25-A resolution indicates that the iron
      porphycene, a structural isomer of hemin, is located in the normal position of
      the heme pocket. Furthermore, it was found that the reconstituted myoglobin
      catalyzed the H2O2-dependent oxidations of substrates such as guaiacol,
      thioanisole, and styrene. At pH 7.0 and 20 degrees C, the initial rate of the
      guaiacol oxidation is 11-fold faster than that observed for the native myoglobin.
      Moreover, the stopped-flow analysis of the reaction of the reconstituted protein
      with H2O2 suggested the formation of two reaction intermediates, compounds II-
      and III-like species, in the absence of a substrate. It is a rare example that
      compound III is formed via compound II in myoglobin chemistry. The enhancement of
      the peroxidase activity and the formation of the stable compound III in myoglobin
      with iron porphycene mainly arise from the strong coordination of the Fe-His93
      bond.

PMID- 17173410
TI  - The influence of amine/amide versus bisamide coordination in nickel superoxide
      dismutase.
AB  - Nickel superoxide dismutase (NiSOD) is a mononuclear nickel-containing
      metalloenzyme that catalyzes the disproportionation of superoxide by cycling
      between NiII and NiIII oxidation states. In the reduced NiII oxidation state, the
      metal center is ligated by two cysteinate sulfurs, one amide nitrogen, and one
      amine nitrogen (from the N-terminus), while in the oxidized NiIII state, an
      imidazole nitrogen coordinates to the metal center. Herein, we expand on a
      previous report in which we described a functional metallopeptide-based NiSOD
      model compound [NiII(SODM1)] (SODM1 = H2N-HCDLPCGVYDPA-COOH) by exploring how
      acylation of the N-terminus (producing [NiII(SODM1-Ac)]) influences the
      properties of the metallopeptide. Titration results, GPC data, and mass
      spectrometry data demonstrate that NiII coordinates to SODM1-Ac in a 1:1 ratio,
      while variable pH studies show that NiII coordination is strong at a pH of 7.5
      and above but not observed below a pH of 6.2. This is higher than [NiII(SODM1)]
      by approximately 1.0 pH unit consistent with bisamide ligation. Ni K-edge XAS
      demonstrates that the NiII center is coordinated in a square-planar NiN2S2
      coordination environment with Ni-N distances of 1.846(4) A and Ni-S distances of
      2.174(3) A. Comparison of the electronic absorption and CD spectrum of
      [NiII(SODM1)] versus [NiII(SODM1-Ac)] in conjunction with time-dependent DFT
      calculations suggests a decrease in Ni covalency in the acylated versus
      unacylated metallopeptide. This decrease in covalency was also supported by DFT
      calculations and Ni L-edge XAS. [NiII(SODM1-Ac)] has a quasireversible NiII/NiIII
      redox couple of 0.49(1) V vs Ag/AgCl, which represents a -0.2 V shift compared
      with [NiII(SODM1)], while the peak separation suggests a change in the
      coordination environment upon oxidation (i.e., axial imidazole ligation). Using
      the xanthine/xanthine oxidase assay, we determine that [NiII(SODM1-Ac)] is less
      active than [NiII(SODM1)] by over 2 orders of magnitude (IC50 = 3(1) x 10-5 vs
      2(1) x 10-7 M). Possible reasons for the decrease in activity are discussed.

PMID- 17173411
TI  - Synthesis and structure of nickel-containing cuboidal clusters derived from
      [W3Se4(H2O)9]4+. Site-differentiated substitution at the nickel site in the
      series [W3NiQ4(H2O)10]4+ (Q = S, Se).
AB  - New Ni-containing heterometallic cuboidal cluster aqua complex
      [W3(NiCl)Se4(H2O)9]3+, the missing link in the family of the M3NiQ4 clusters (M =
      Mo, W; Q = S, Se), has been prepared by the reaction of [W3Se4(H2O)9]4+ with Ni
      in 2 M HCl. Single crystals of edge-linked double-cuboidal cluster
      [{W3NiSe4(H2O)9}2](pts)8.18H2O (pts = p-toluenesulfonate) were grown from the
      solution of the aqua complex in 3 M Hpts, and their structures were determined.
      The Ni site in the clusters [W3(NiCl)Q4(H2O)9]3+ selectively coordinates typical
      pi-acceptor ligands such as CO, olefins, acetylenes, phosphines, arsines, or
      SnCl3-. This allows stabilization by coordination of such elusive species as
      HP(OH)2 and As(OH)3. The stability constants for coordination of HP(OH)2,
      As(OH)3, and SnCl3- were determined. The Se for S substitution increases the
      stability by 1-2 orders of magnitude. Supramolecular adducts with cucurbit[6]uril
      (Cuc), [W3(Ni(HP(OH)2))Q4(H2O)9]Cl4.Cuc.11H2O and
      [W3(NiAs(OH)3)S4(H2O)8Cl]Cl3.Cuc.13H2O, were isolated and structurally
      characterized.

PMID- 17173412
TI  - Electronic transitions involved in the absorption spectrum and dual luminescence
      of tetranuclear cubane [Cu4I4(pyridine)4] cluster: a density functional
      theory/time-dependent density functional theory investigation.
AB  - We present a combined density functional theory (DFT)/time-dependent density
      functional theory (TDDFT) study of the geometry, electronic structure, and
      absorption and emission properties of the tetranuclear "cubane" Cu4I4py4 (py =
      pyridine) system. The geometry of the singlet ground state and of the two lowest
      triplet states of the title complex were optimized, followed by TDDFT excited
      state calculations. This procedure allowed us to characterize the nature of the
      excited states involved in the absorption spectrum and those responsible for the
      dual emission bands observed for this complex. In agreement with earlier
      experimental proposals, we find that while in absorption the halide-to-pyridine
      charge-transfer excited state (XLCT*) has a lower energy than the cluster
      centered excited state (CC*), a strong geometrical relaxation on the triplet
      cluster-centered state surface leads to a reverse order of the excited states in
      emission.

PMID- 17173413
TI  - Two- and three-dimensional networks of gadolinium(III) with dicarboxylate
      ligands: synthesis, crystal structure, and magnetic properties.
AB  - Four gadolinium(III) complexes with dicarboxylate ligands of formulas
      [Gd2(mal)3(H2O)5]n.2nH2O (1), [Gd2(mal)3(H2O)6]n (2), [NaGd(mal)(ox)(H2O)3]n (3),
      and [Gd2(ox)3(H2O)6]n.2.5nH2O (4) (mal = malonate; ox = oxalate) have been
      prepared, and their magnetic properties have been investigated as a function of
      the temperature. The structures of 1-3 have been determined by X-ray diffraction
      methods. The crystal structure of 4 was already known, and it is made of
      hexagonal layers of Gd atoms that are bridged by bis-bidentate oxalate. Compound
      1 is isostructural with the europium(III) malonate complex
      [Eu2(mal)3(H2O)5]n.2nH2O,1 whose structure was reported elsewhere. The Gd atoms
      in 1 define a two-dimensional network where a terminal bidentate and bridging
      bidentate/bis-monodentate and tris-bidentate coordination modes of malonate
      occur. Compound 2 has a three-dimensional structure with a structural phase
      transition at 226 K, which involves a change of the space group from I2/a to Ia.
      Although its structure at room temperature was already known, that below 226 K
      was not. Pairs of Gd atoms with a double oxo-carboxylate bridge occur in both
      phases, and the main differences between both structures deal with the Gd
      environment and the H-bond pattern. 3 is also a three-dimensional compound, and
      it was obtained by reacting Gd(III) ions with malonic acid in a silica gel
      medium. Oxalic acid results as an oxidized product of the malonic acid, and
      single crystals of the heteroleptic complex were produced. The Gd atoms in 3 are
      connected through bis-bidentate oxalate and carboxylate-malonate bridges in the
      anti-anti and anti-syn coordination modes. Compounds 1 and 2 exhibit weak but
      significant ferromagnetic couplings between the Gd(III) ions through the single
      (1) and double (2) oxo-carboxylate bridges, whereas antiferromagnetic
      interactions across the bis-bidentate oxalate account for the overall
      antiferromagnetic behavior observed in 3 and 4.

PMID- 17173414
TI  - Donor-acceptor interactions and electron transfer in cyano-bridged trinuclear
      compounds.
AB  - The NIR donor-acceptor charge transfer (DACT) bands of the series of trinuclear
      complexes trans-[(NC)5Fe(II/III)(mu-CN)RuIIL4(mu-NC)FeIII(CN)5](5/4-) (L=
      pyridine, 4-tert-butylpyridine, and 4-methoxypyridine) are analyzed in terms of a
      simplified molecular orbital picture that reflects the interaction between the
      donor and acceptor fragments. The degree of electronic coupling between the
      fragments is estimated by a full fit of the DACT band profiles according to a
      three-state model inspired in the Mulliken-Hush formalism. The information is
      complemented with determinations performed on the asymmetric heterotrinuclear
      species trans-[(NC)5CoIII(mu-CN)RuII(py)4(mu-NC)FeIII(CN)5]4-, whose preparation
      is reported here for the first time. The analysis of the NIR spectra of the
      symmetric trans-[(NC)5FeIII(mu-CN)RuIIL4(mu-NC)FeIII(CN)5]4- species reveals a
      low degree of mixing between the terminal acceptor fragments and the bridging
      moiety containing RuII, with H12 values between 1.0 x 10(3) and 1.5 x 10(3) cm-1.
      The reorganization energy contributions seem to be the same for the three
      species, even when the spectra were recorded in different media. This observation
      also applies for the CoIII-substituted compound. The computed potential energy
      surfaces (PES) of the ground state for these complexes show only one stationary
      point, suggesting that the FeII-RuIII-FeIII (or FeII-RuIII-CoIII) electronic
      isomers are not thermally accessible. One-electron reduction leads to asymmetric
      trans-[(NC)5FeII(mu-CN)RuIIL4(mu-NC)FeIII(CN)5]5- compounds with potentially two
      DACT bands involving the RuII and the FeII donor fragments. These species reveal
      a similar degree of electronic mixing but the PES shows three minima. We explore
      the role of the bridging fragment in the long-range thermally induced electron
      transfer between the distant iron centers. The results suggest that superexchange
      and hopping might become competitive paths, depending on the substituents in the
      bridging fragment.

PMID- 17173415
TI  - Structural diversity of silver(I) 4,6-dipyridyl-2-aminopyrimidine complexes:
      effect of counteranions and ligand isomerism.
AB  - Using two ligands, 4,6-bis(2-pyridyl)-2-aminopyrimidine (L1) with two N,N'
      chelating sites and 4-(2-pyridyl)-6-(4-pyridyl)-2-aminopyrimidine (L2) (as the
      isomer of L1) containing one chelating site and one bridging unit, a series of
      novel Ag(I) complexes varying from zero- to two-dimensions have been prepared and
      their crystal structures determined via single-crystal X-ray diffraction. The two
      ligands are employed for the first time in coordination chemistry. The structures
      of compounds 1-3 are directed by the counteranions adopted in the reaction
      system: The reaction of L1 with AgNO3 yielded a dimer [Ag2L12](NO3)2 (1). The
      reaction of L1 with AgCF3SO3 led to a one-dimension "V-shaped" chain
      {[AgL1](CF3SO3)}n (2). When AgSCN was used, a one-dimension ladder
      {[Ag2L1(SCN)2].H2O}n (3) was obtained. While ligand L2 reacted with AgNO3, a two
      dimension {[Ag2(L2)2](NO3)2.H2O}n (4) was prepared with the help of an
      argentophilic interaction. Compounds 1-4 display room-temperature
      photoluminescence.

PMID- 17173416
TI  - Ag(I) and Cu(II) discrete and polymeric complexes based on single- and double
      armed oxadiazole-bridging organic clips.
AB  - Four new oxadiazole-bridging ligands (L1-L4) were designed and synthesized by the
      reaction of 2,5-bis(2-hydroxyphenyl)-1,3,4-oxadiazole with isonicotinoyl chloride
      and nicotinoyl chloride, respectively. L1 and L3 are unsymmetric single-armed
      ligands (4- or 3-pyridinecarboxylate arm), and L2 and L4 are symmetric double
      armed ligands (4- or 3-pyridinecarboxylate arms). Nine new complexes,
      [Ag(L1)]PF6.CH3OH (1), [Ag(L1)]ClO4.CH3OH (2), Cu(L2)(NO3)2.2(CH2Cl2) (3),
      [Cu(L2)2](ClO4)2.2(CH2CCl2) (4), Cu(L2)Cl2 (5), [Cu4(L3)2(H2O)2](L3)4(ClO4)4 (6),
      [Ag(L4)(C2H5OH)]ClO4 (7), [Ag(L4)(C2H5OH)]BF4 (8), and [Ag(L4)(CH3OH)]SO3CF3 (9),
      were isolated from the solution reactions based on these four new ligands,
      respectively. L1, L2, and L3 act as convergent ligands and bind metal ions into
      discrete molecular complexes. In contrast, L4 exhibits a divergent spacer to link
      metal ions into one-dimensional coordination polymers. New coordination compounds
      were fully characterized by infrared spectroscopy, elemental analysis, and single
      crystal X-ray diffraction. In addition, the luminescent and electrical conductive
      properties of these new compounds were investigated.

PMID- 17173417
TI  - Polyoxometalate (W/Mo) compounds connected via lanthanide cations with a three
      dimensional framework, H2{[K(H2O)2]2[Ln(H2O)5]2(H2M12O42)}.nH2O: synthesis,
      structures, and magnetic properties.
AB  - A series of 10 novel polyoxometalate (W/Mo) compounds connected via a trivalent
      lanthanide cation bridge, H2{[K(H2O)2]2[Ln(H2O)5]2(H2M12O42)}.n(H2O) (Ln = La,
      Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, Lu; M = W or W/Mo) (1-10), were designed and
      synthesized on the basis of the abduction of Al3+ in aqueous solution. X-ray
      diffraction analyses reveal that the structures of complexes 1-10 are three
      dimensional frameworks assembled from the arrangement of H2M12O42(10-) (named
      paradodecmetalate-B) and Ln(H2O)53+ with two planes, which are constructed via
      the unification of H2M12O42(10-) and Ln(H2O)53+, along the [100] and [001]
      directions. Magnetic measurements reveal the paramagnetic properties and a strong
      ferromagnetic coupling between the two nearest-neighboring lanthanide cations,
      Ln3+ (Ln = Dy, Er), within the circle for compounds 2 and 4-9.

PMID- 17173419
TI  - Incorporation, oxidation and pyrolysis of ferrocene into porous silica glass: a
      route to different silica/carbon and silica/iron oxide nanocomposites.
AB  - This work reports the incorporation of ferrocene into a porous silica glass under
      ambient temperature and atmosphere. After or during the ferrocene incorporation,
      the spontaneous formation of ferricinium ions was observed by electron
      paramagnetic resonance (EPR), UV-visible, X-ray absorption near-edge structure
      (XANES), and 57Fe Mossbauer measurements. It was shown that the oxidation of
      ferrocene molecules to ferricinium ions was promoted by air and that the Si-O-
      groups on the surface of the pores act as counteranions. Pyrolysis of the porous
      glass/ferricinium material under argon atmosphere and variable temperature yields
      different glass/carbon nanocomposites, which were subsequently treated with an HF
      solution in order to remove the glassy fraction. The resulting insoluble carbon
      materials were characterized by transmission electron microscopy (TEM), Raman,
      and EPR spectroscopy and consisted of amorphous carbon when the pyrolysis was
      carried out at 900 or 1000 degrees C and of a mixture of carbon nanotubes and
      carbonaceous materials at a pyrolysis temperature of 1100 degrees C. When the
      pyrolysis was conducted under air, the incorporated ferricinium forms alpha
      Fe2O3, and the resulting material is a transparent and highly homogeneous
      glass/iron oxide nanocomposite.

PMID- 17173418
TI  - 19F high magnetic field NMR study of beta-ZrF4 and CeF4: from spectra
      reconstruction to correlation between fluorine sites and 19F isotropic chemical
      shifts.
AB  - High magnetic field and high spinning frequency one- and two-dimensional one
      pulse MAS 19F NMR spectra of beta-ZrF4 and CeF4 were recorded and reconstructed
      allowing the accurate determination of the 19F chemical shift tensor parameters
      for the seven different crystallographic fluorine sites of each compound. The
      attributions of the NMR resonances are performed using the superposition model
      for 19F isotropic chemical shift calculation initially proposed by Bureau et al.
      (Bureau, B.; Silly, G.; Emery, J.; Buzare, J.-Y. Chem. Phys. 1999, 249, 85-104).
      A satisfactory reliability is reached with a root-mean-square (rms) deviation
      between calculated and measured isotropic chemical shift values equal to 1.5 and
      3.5 ppm for beta-ZrF4 and CeF4, respectively.

PMID- 17173420
TI  - Synthesis, crystal structure, and luminescent properties of novel Eu3+
      heterocyclic beta-diketonate complexes with bidentate nitrogen donors.
AB  - New tris(heterocyclic beta-diketonato)europium(III) complexes of the general
      formula Eu(PBI)3.L [where HPBI = 3-phenyl-4-benzoyl-5-isoxazolone and L = H2O,
      2,2'-bipyridine (bpy), 4,4'-dimethoxy-2,2'-bipyridine (dmbpy), 1,10
      phenanthroline (phen), or 4,7-diphenyl-1,10-phenanthroline (bath)] were
      synthesized and characterized by elemental analysis, Fourier transform infrared
      spectroscopy (FT-IR), 1H NMR, high-resolution mass spectrometry,
      thermogravimetric analysis, and photoluminescence (PL) spectroscopy. Single
      crystal X-ray structures have been determined for the complexes Eu(PBI)3.H2O.EtOH
      and Eu(PBI)3.phen. The complex Eu(PBI)3.H2O.EtOH is mononuclear, and the central
      Eu3+ ion is coordinated by eight oxygen atoms to form a bicapped trigonal prism
      coordination polyhedron. Six oxygens are from the three bidentate HPBI ligands,
      one is from a water molecule, and another is from an ethanol molecule. On the
      other hand, the crystal structure of Eu(PBI)3.phen reveals a distorted square
      antiprismatic geometry around the europium atom. The room-temperature PL spectra
      of the europium(III) complexes are composed of the typical Eu3+ red emission,
      assigned to transitions between the first excited state (5D0) and the multiplet
      (7F0-4). The results demonstrate that the substitution of solvent molecules by
      bidentate nitrogen ligands in Eu(PBI)3.H2O.EtOH richly enhances the quantum yield
      and lifetime values. To elucidate the energy transfer process of the europium
      complexes, the energy levels of the relevant electronic states have been
      estimated. Judd-Ofelt intensity parameters (Omega2 and Omega4) were determined
      from the emission spectra for Eu3+ ion based on the 5D0 --> 7F2 and 5D0 --> 7F4
      electronic transitions, respectively, and the 5D0 --> 7F1 magnetic dipole allowed
      transition was taken as the reference. The high values obtained for the 4f-4f
      intensity parameter Omega2 for europium complexes suggest that the dynamic
      coupling mechanism is quite operative in these compounds.

PMID- 17173421
TI  - Linear and pre-organized carboxylic acid picket porphyrins as bismuth chelators.
AB  - New picket porphyrins delivering at least one carboxylic group around the
      coordination site of the macrocycle were synthesized for bismuth coordination.
      The influence of the number, the length, and the pre-organization of the
      carboxylic acid pickets on the stability of the bismuth complexes was explored.
      Their stabilities in acidic medium were compared with those of their precursors
      bearing ester pickets. The molecular structure of one of the bismuth complexes,
      which is the only monomeric bismuth porphyrin reported up to now, is discussed.
      At the opposite of what we initially reported, and in agreement with the
      theoretical calculations, the distortion of the macrocycle in this structure is
      mainly due to the number of water molecules in the first sphere of coordination
      of the bismuth.

PMID- 17173422
TI  - Synthesis and spectroscopic properties of platinum(II) terpyridine complexes
      having an arylborane charge transfer unit.
AB  - Synthesis, redox, spectroscopic, and photophysical properties of a new class of
      Pt(II) complexes of the type [PtLnCl]+ are reported, where Ln is 4'
      phenyl(dimesitylboryl)-2,2':6',2"-terpyridine (L1) or 4'-duryl(dimesitylboryl)
      2,2':6',2"-terpyridine (L2). The free L1 or L2 ligand in CH3CN shows the
      absorption band responsible for intramolecular charge transfer (CT) from the pi
      orbital of the aryl group in L1 or L2 (pi(aryl)) to the vacant p-orbital on the
      boron atom (p(B)), in addition to pipi* absorption in the 2,2':6',2"-terpyridine
      (tpy) unit. In particular, the L1 ligand shows an intense CT absorption band as
      compared with L2. Such intramolecular pi(aryl)-p(B) CT interactions in L1 give
      rise to large influences on the redox, spectroscopic, and photophysical
      properties of [PtL1Cl]+. In practice, [PtL1Cl]+ shows strong room-temperature
      emission in CHCl3 with the quantum yield and lifetime of 0.011 and 0.6 micros,
      respectively, which has been explained by synergetic effects of Pt(II)-to-L1 MLCT
      and pi(aryl)-p(B) CT interactions on the electronic structures of the complex. In
      the case of [PtL2Cl]+, the dihedral angle between the planes produced by the tpy
      and duryl(dimesitylborane) groups is very large (84 degrees ) as compared with
      that between the tpy and phenyl(dimesitylborane) units in [PtL1Cl]+ (26-39
      degrees ), which disturbs electron communication between the Pt(II)-tpy and
      arylborane units in [PtL2Cl]+. Thus, [PtL2Cl]+ is nonemissive at room
      temperature. The important roles of the synergetic CT interactions in the excited
      state properties of the [PtL1Cl]+ complex are shown clearly by emission quenching
      of the complex by a fluoride ion. The X-ray crystal structure of [PtL1Cl]+ is
      also reported.

PMID- 17173423
TI  - Synthesis, spectroscopic, and structural investigation of the cyclic [N(PR2E)2]+
      cations (E = Se, Te; R = iPr, Ph): the effect of anion and R-group exchange.
AB  - Two-electron oxidation of the [N(PiPr2E)2]- anion with iodine produces the cyclic
      [N(PiPr2E)2]+ (E =Se, Te) cations, which exhibit long E-E bonds in the iodide
      salts [N(PiPr2Se)2]I (4) and [N(PiPr2Te)2]I (5). The iodide salts 4 and 5 are
      converted to the ion-separated salts [N(PiPr2Se)2]SbF6 (6) and [N(PiPr2Te)2]SbF6
      (7) upon treatment with AgSbF6. Compounds 4-7 were characterized in solution by
      multinuclear NMR, vibrational, and UV-visible spectroscopy supported by DFT
      calculations. A structural comparison of salts 4-7 and [N(PiPr2Te)2]Cl (8)
      confirms that the long E-E bonds in 4, 5, and 8 can be attributed primarily to
      the donation of electron density from a lone pair of the halide counterion into
      the E-E sigma* orbital (LUMO) of the cation. The phenyl derivative [N(PPh2Te)2]I
      (9) was prepared in a similar manner. However, the attempted synthesis of the
      selenium analogue, [N(PPh2Se)2]I, produced a 1:1 mixture of [N(PPh2Se)2(mu
      Se)][I] (10) and [SeP(Ph2)N(Ph2)PI] (11). DFT calculations of the formation
      energies of 10 and 11 support the observed decomposition. Compound 10 is a
      centrosymmetric dimer in which two six-membered NP2Se3 rings are bridged by two I
      anions. Compound 11 produces the nine-atom chain {[N(PPh2)2Se]2(mu-O)} (12) upon
      hydrolysis during crystallization. The reaction between [(TMEDA)NaN(PiPr2Se)2]
      and SeCl2 in a 1:1 molar ratio yields the related acyclic species
      [SeP(iPr2)N(iPr2)PCl] (13), which was characterized by multinuclear NMR
      spectroscopy and an X-ray structural determination.

PMID- 17173424
TI  - Luminescent dipyrrinato complexes of trivalent group 13 metal ions.
AB  - Although free dipyrrins (dipyrromethenes) do not strongly luminesce, certain
      dipyrrinato complexes of BF2 and zinc(II) are known to be intensely luminescent
      species. Two new dipyrrinato fluorophores, based on complexes with gallium(III)
      and indium(III), are described. Using a previously described meso-mesityl
      substituted dipyrrin, namely 5-mesityldipyrrin (mesdpm), the complexes
      [Ga(mesdpm)3] and [In(mesdpm)3] were prepared and structurally characterized. The
      complexes display the expected octahedral geometry about the metal ions. In some
      solvents, such as hexanes, the complexes emit green light upon excitation with UV
      light at room temperature, with quantum yields of 2.4% ([Ga(mesdpm)3]) and 7.4%
      ([In(mesdpm)3]) and lifetimes in the low nanosecond range. Observations are
      consistent with assignment to ligand-localized transitions, and this
      interpretation is further confirmed by density functional calculations described
      herein. The new complexes are important additions to the widely used family of
      dipyrrin-based fluorescent species and show that dipyrrinato complexes containing
      metals other than BF2 and zinc(II) may be useful fluorophores.

PMID- 17173425
TI  - Coordination preference of Ga in hydrides.
AB  - Aluminum and gallium show some interesting differences in their coordination
      chemistry. Solid GaH3 is unknown, in contrast to solid AlH3. Ga equivalents of
      Li3AlH6, Na3AlH6, and other hydrides whose structure contain AlH(3-)6 ions, are
      unknown. We relate these differences to an instability of the hexacoordinated
      gallium moiety.

PMID- 17173426
TI  - Construction of polyoxometalates-based coordination polymers through direct
      incorporation between polyoxometalates and the voids in a 2D network.
AB  - A series of polyoxometalates (POMs)-based coordination polymers, namely, {[Cu(2,3
      Me2pz)(2,5-Me2pz)0.5]4(SiW12O40)(2,5-Me2pz)}n (2,3-Me2pz = 2,3-dimethylpyrazine;
      2,5-Me2pz = 2,5-dimethylpyrazine; 1), {[Cu2(4,4'-bipy)4(H2O)4](SiW12O40)(H2O)18}n
      (4,4'-bipy = 4,4'-bipyridine; 2), {[Cu(2-Mepz)1.5]3(PMo12O40)(H2O)3.5}n (2-Mepz =
      2-methylpyrazine; 3), {[Ag(2,3-Me2pz)1.5]4(SiW12O40}n (4),
      {[Cu(pz)1.5]4(SiW12O40)(H2O)3}n (pz = pyrazine; 5), {[Cu(2,3
      Me2pz)1.5]4(SiW12O40)}n (6), {[Cu(4,4'-bipy)1.75]4(SiW12O40)(H2O)2}n (7), and
      {[Cu2(4,4'-bipy)4(H2O)4](SiW12O40)(4,4'-bipy)2(H2O)4}n (8), were synthesized
      through direct incorporation between POMs and the voids of the 2D network.
      Crystal structural analysis reveals that the relationship between the size of the
      void of the 2D network and that of POMs is of key importance for successful
      synthesis of POMs-based open metal-organic frameworks. Guest replacement shows
      that the pore size of the framework constructed through direct incorporation
      between POMs and the voids of the 2D network is very sensitive to guest
      molecules.

PMID- 17173427
TI  - Activation of atmospheric nitrogen and azobenzene N=N bond cleavage by a
      transient Nb(III) complex.
AB  - Atmospheric N2 is activated by two transient Nb(III) "(PNP)NbCl2" (PNP- = N[2
      P(CHMe2)2-4-methylphenyl]2) fragments to form the bridging diimido
      [(PNP)NbCl2]2(mu-N2) (1). Complex 1 can also be independently synthesized from
      Nb(IV) and Nb(V) precursors via one-electron and transmetalation reactions,
      respectively. In the presence of azobenzene, the transient Nb(III) intermediate,
      prepared from Li(PNP) and NbCl3(DME) (DME = dimethoxyethane) under Ar, cleaves
      the N=N bond via a metal-ligand cooperative four-electron reduction to form
      niobium imide and phosphoranimine functionalities. Structural studies are
      presented and discussed for various Nb systems bearing the pincer-type framework
      PNP as well as the N2 and azobenzene activated products. Theoretical studies
      addressing the Nb-N2-Nb core in 1 are also presented.

PMID- 17173428
TI  - Metal-organic frameworks from zinc sulfite clusters, chains, and sheets: 4
      connected, (3,4)-connected 3-D frameworks and 2-D arrays of catenane-like
      interlocking rings.
AB  - Even though open-framework solids have been made in a variety of compositions
      such as silicates, phosphates, germanates, borates, and phosphites, few are known
      that are based on trigonal-pyramidal sulfite anions. We report here the first
      synthetic and structural studies of metal-organic framework materials in the zinc
      sulfite composition. It is demonstrated here that Zn2+ and SO32- can form various
      neutral inorganic subunits that can be 0-D clusters, 1-D chains, or 2-D sheets.
      These inorganic subunits of different dimensionality can subsequently be
      connected into extended frameworks of higher dimensionality through bifunctional
      ligands. In (ZnSO3)2en, infinite corrugated ZnSO3 layers are pillared by
      ethylenediamine (en) molecules into a 3-D network that can be classified as a
      (3,4)-connected net based on tetrahedral Zn nodes and trigonal-pyramidal S nodes.
      In (ZnSO3)pip, infinite ZnSO3 chains are cross-linked with piperazine molecules
      into a 3-D framework that can be classified as 4-connected net based on
      tetrahedral Zn nodes only. In (ZnSO3)2(TMDPy)2, (ZnSO3)2 dimers are doubly
      bridged by trimethylenedipyridine molecules into an infinite chain with a string
      of circles. Each circle along the chain is interlocked with another circle from a
      chain in the perpendicular direction, creating a 2-D pattern with an infinite
      square array of catenane-like units.

PMID- 17173429
TI  - La2TeI2: a new layered telluride iodide with unusual electrical properties.
AB  - A new layered metal-rich telluride halide, La2TeI2, has been synthesized by
      heating stoichiometric mixtures of LaI3, La, and Te under argon at 900 degrees C,
      and its structure has been refined from X-ray powder diffraction data. The
      compound crystallizes in the 3R-Lu2CCl2 structure type (rhombohedral space group
      R(-)3m with a = 4.5074(4) A, c = 32.528(2) A, and Z = 3). The crystal structure
      is composed of infinite layers of edge-sharing, Te-centered metal atom octahedra
      and iodine atoms separating these layers to form three close-packed I-Ln-Te-Ln-I
      slabs within the unit cell. The title compound is metallic at room temperature
      and exhibits an anomaly in the resistivity around 140 K which is closely related
      to changes in the a lattice parameter with temperature. The chemical bonding and
      metallic properties of La2TeI2 can be plausibly understood in terms of an ionic
      description (Ln3+)2Te2-(I-)2(e)2 where two electrons are delocalized in the La 5d
      conduction band.

PMID- 17173430
TI  - Bis(1 degree-amino)cyclodistib(III)azanes: the first structural characterization
      of cis and trans isomers of a single cyclodipnict(III)azane.
AB  - The dichlorocyclodistib(III)azane [ClSb(mu-NtBu)]2 (1) has been shown to exist as
      the cis isomer in the solid state. A series of bis(1 degree
      amino)cyclodistib(III)azanes [R'NHSb(mu-NtBu)]2 (2, R' = tBu; 3, R' = Dipp; 4, R'
      = Dmp) has been prepared by the reaction of 1 with 2 equiv. of LiNHR'. On the
      basis of NMR solution spectra, all three derivatives are formed as a mixture of
      cis and trans isomers. In the case of 3, the structures of both the cis and trans
      isomers have been determined by X-ray crystallography; cis-3 adopts an endo, endo
      arrangement for the amido protons of the DippNH groups. Isomerization of trans-3
      into cis-3 occurs slowly in solution. Deprotonation of 2 with 2 equiv. of nBuNa
      or trans-3 with nBuLi produces [Na2Sb2(mu-NtBu)4] (5) and [Li2Sb2(mu-NtBu)2(mu
      NDipp)2] (6), whose solvated cubane structures were established by X-ray
      crystallography. In contrast, the reaction of cis-3 with 2 equiv. of nBuLi
      produces the tricyclic compound [Li2Sb(mu-NtBu)2(mu-NDipp)(mu-NHDipp)] (7).

PMID- 17173431
TI  - Spin dimer analysis of the magnetic structures of Ba3Cr2O8, Ba3Mn2O8, Na4FeO4,
      and Ba2CoO4 with a three-dimensional network of isolated MO4 (M = Cr, Mn, Fe, Co)
      tetrahedra.
AB  - The spin exchange interactions of the magnetic oxides Ba3Cr2O8, Ba3Mn2O8,
      Na4FeO4, and Ba2CoO4 with a three-dimensional network of isolated MO4 (M = Cr,
      Mn, Fe, Co) tetrahedra were examined by performing spin dimer analysis on the
      basis of tight-binding electronic structure calculations. Although the shortest
      O...O distances between adjacent MO4 tetrahedra are longer than the van der Waals
      distance, our analysis shows that the super-superexchange interactions between
      adjacent MO4 tetrahedra are substantial and determine the magnetic structures of
      these oxides. In agreement with experiment, our analysis predicts a weakly
      interacting isolated AFM dimer model for both Ba3Cr2O8 and Ba3Mn2O8, the (0.0,
      0.5, 0.0) magnetic superstructure for Na4FeO4, the (0.5, 0.0, 0.5) magnetic
      superstructure for Ba2CoO4, and the presence of magnetic frustration in Ba2CoO4.
      The comparison of the intra- and interdimer spin exchange interactions of
      Ba3Cr2O8 and Ba3Mn2O8 indicates that orbital ordering should be present in
      Ba3Cr2O8.

PMID- 17173432
TI  - Built-in axial base binding on phenanthroline-strapped zinc(II) and iron(III)
      porphyrins.
AB  - In addition to the need for functional models of cytochrome c oxidase, structural
      models are still required for a better understanding of the small reorganizations
      occurring during the catalytic cycle. An efficient synthetic approach has been
      designed to prepare several phenanthroline-strapped porphyrins, two of them
      bearing two pendant imidazoles. These built-in bases are both potentially able to
      act as axial bases for the metalloporphyrin and as complementary ligands for
      copper if necessary. Diamagnetic zinc(II) was used to demonstrate that the
      distal/proximal selectivity demonstrated by exogenic bases binding studies can be
      extended to the coordination of iron(III). Combination of EPR and paramagnetic 1H
      NMR shows that the imidazole binding on the zinc species can be further extended
      to the iron(III) species in dilute conditions.

PMID- 17173433
TI  - First hydrolysis constants of hexaaquacobalt(III) and -manganese(III):
      longstanding issues resolved.
AB  - The acid dissociation constants, Kh, of the hexaaquacobalt(III) and 
      manganese(III) ions are reported under conditions which minimize the problems of
      instability of these species at modest acidities (pH 1-4). A rapid and convenient
      preparation of aqueous Co(III) has been used, and the latter has been reacted
      with aqueous Mn(II) to form aqueous Mn(III). The noncoordinating buffer H2PIPPS
      (1,4-bis(3-sulfopropyl)piperazine) has been used to react with H+ and provide
      some control of the pH. Spectrophotometric changes, after stopped-flow mixing for
      Co(III) and conventional mixing for Mn(III), were used to determine the Kh
      values. The pKh values are as follows: Co(III), 3.10 +/- 0.07 (6.0 degrees C) and
      2.92 +/- 0.04 (20.0 degrees C) in 1.0 M H+, Na+, ClO4-; Mn(III), 0.22 +/- 0.04
      (7.6 degrees C) and 0.08 +/- 0.04 (20.0 degrees C) in approximately 4 M H+, Mn2+,
      ClO4-. Global fits of the data for each metal have been used to estimate the
      DeltaH degree and DeltaS degree values for Kh. It is suggested that the unusually
      high acidity of Mn(OH2)6(3+) may be due to a Jahn-Teller distortion effect.

PMID- 17173434
TI  - Syntheses, structures, and magnetic properties of mononuclear CuII and
      tetranuclear CuII3MII (M = Cu, Co, or Mn) compounds derived from N,N'
      ethylenebis(3-ethoxysalicylaldimine): cocrystallization due to potential
      encapsulation of water.
AB  - Syntheses, structures, and magnetic properties of one mononuclear inclusion
      compound [CuIIL1 within (H2O)] (1) and three tetrametal systems of the
      composition [{CuIIL1}2{CuIIL1MII(H2O)3}]ClO4)2 (M = Cu (2), M = Co (3), M = Mn
      (4)) derived from the hexadentate Schiff base compartmental ligand N,N'
      ethylenebis(3-ethoxysalicylaldimine) (H2L1) have been described. Compounds 1 and
      2 crystallize in orthorhombic Pbcn and monoclinic P21/c systems, respectively,
      and the space group of the isomorphous compounds 3 and 4 is monoclinic C2/c. The
      water molecule in 1 is encapsulated in the vacant O4 compartment because of the
      hydrogen bonding interactions with the ether and phenolate oxygens, resulting in
      the formation of an inclusion product. The structures of 2-4 consist of the
      [CuIIL1MII(H2O)3]2+ cation and two mononuclear [CuIIL1] moieties. In the
      dinuclear [CuIIL1MII(H2O)3]2+ cation, the metal centers are doubly bridged by the
      two phenolate oxygens. The second metal center, MII (Cu in 2, Co in 3, and Mn in
      4), in the [CuIIL1MII(H2O)3]2+ cation is pentacoordinated by the two phenoxo
      oxygens and three water molecules. Two of these three coordinated water molecules
      interact, similar to that in 1, with two mononuclear [CuIIL1] moieties, resulting
      in the formation of the tetrametal [{CuIIL1}2{CuIIL1MII(H2O)3}]2+ system that
      consists of the cocrystallized dinuclear (one) and mononuclear (two) moieties.
      Evidently, the cocrystallization observed in 2-4 is related to the tendency of a
      water molecule to be encapsulated in the vacant O4 compartment of the mononuclear
      [CuIIL1] species. In the case of 2, there are two independent
      [CuIIL1CuII(H2O)3]2+ units. The tau ((beta-alpha)/60, where beta and alpha are
      the largest and second largest bond angles, respectively) values in the
      pentacoordinated environment of the two copper(II) centers in 2 are 0.04 and
      0.37, indicating almost ideal and appreciably distorted square pyramidal
      geometry, respectively. In contrast, the tau values (0.54 for 3 and 0.49 for 4)
      indicate that the coordination geometry around the cobalt(II) and manganese(II)
      centers in 3 and 4 is intermediate between square pyramidal and trigonal
      bipyramidal. The variable-temperature (2-300 K) magnetic susceptibilities of
      compounds 2-4 have been measured. The magnetic data have been analyzed in the
      model of one exchange-coupled dinuclear CuIIMII moiety and two noninteracting
      CuII centers. In all three cases, the metal ions in the dinuclear core are
      coupled by a weak antiferromagnetic interaction (J = -17.4 cm-1, -8 cm-1, and -14
      cm-1 for 2, 3, and 4, respectively). The observation of a weak interaction has
      been explained in terms of the structural parameters and symmetry of the magnetic
      orbitals.

PMID- 17173435
TI  - Synthesis of CdSnO(3).3H(2)O nanocubes via ion exchange and their thermal
      decompositions to cadmium stannate.
AB  - Uniform crystalline CdSnO3.3H2O nanocubes with a 28-35 nm edge length have been
      obtained via the ion-exchange reaction of Na2Sn(OH)6 in a CdSO4 aqueous solution,
      assisted by ultrasonic treatment. Precursor Na2Sn(OH)6 crystals were prepared via
      hydrothermal treatment in an ethanol/water solution. The formation of CdSnO3.3H2O
      nanocubes resulted from the strain during the ion-exchange process. The
      influences of reaction conditions, such as ion-exchange (ultrasonic treatment)
      duration, solvent constitutes, surfactant, and pH on the formation of CdSnO3.3H2O
      crystals were described. Crystalline CdSnO3 and Cd2SnO4 have been obtained by
      thermal treatment at 300 and 500 degrees C, respectively, for 5 h under an inert
      gas protecting condition using CdSnO3.3H2O nanocubes as the precursor. The cube
      shape of CdSnO3.3H2O was sustained after thermal decomposition to CdSnO3.

PMID- 17173436
TI  - Density functional theory-based prediction of some aqueous-phase chemistry of
      superheavy element 111. Roentgenium(I) is the "softest" metal ion.
AB  - A previous approach (Hancock, R. D.; Bartolotti, L. J. Inorg. Chem. 2005, 44,
      7175) using DFT calculations to predict log K1 (formation constant) values for
      complexes of NH3 in aqueous solution was used to examine the solution chemistry
      of Rg(I) (element 111), which is a congener of Cu(I), Ag(I), and Au(I) in Group
      1B. Rg(I) has as its most stable presently known isotope a t(1/2) of 3.6 s, so
      that its solution chemistry is not easily accessible. LFER (Linear free energy
      relationships) were established between DeltaE(g) calculated by DFT for the
      formation of monoamine complexes from the aquo ions in the gas phase, and
      DeltaG(aq) for the formation of the corresponding complexes in aqueous solution.
      For M2+, M3+, and M4+ ions, the gas-phase reaction was [M(H2O)6]n+(g) + NH3(g) =
      [M(H2O)5NH3]n+(g) + H2O(g) (1), while for M+ ions, the reaction was [M(H2O)2]+(g)
      + NH3(g) = [M(H2O)NH3]+(g) + H2O(g) (2). A value for DeltaG(aq) and for DeltaE
      for the formation of M = Cu2+ in reaction 1, not obtained previously, was
      calculated by DFT and shown to correlate well with the LFER obtained previously
      for other M2+ ions, supporting the LFER approach used here. The simpler use of
      DeltaE values instead of DeltaG(aq) values calculated by DFT for formation of
      monoamine complexes in the gas phase leads to LFER as good as the DeltaG-based
      correlations. Values of DeltaE were calculated by DFT to construct LFER with M+ =
      H+, and the Group 1B metal ions Cu+, Ag+, Au+, and Rg+, and with L = NH3, H2S,
      and PH3 in reaction 3: [M(H2O)2]+(g) + L(g) = [M(H2O)L]+g) + H2O(g) (3).
      Correlations involving DeltaE calculated by DMol3 for H+, Cu+, Ag+, and Au+ could
      reliably be used to construct LFER and estimate unknown log K1 values for Rg(I)
      complexes of NH3, PH3, and H2S calculated using the ADF (Amsterdam Density
      Functional) code. Log K1 values for Rg(I) complexes are predicted that suggest
      the Rg(I) ion to be a very strong Lewis acid that is extremely "soft" in the
      Pearson hard and soft acids and bases sense.

PMID- 17173437
TI  - Li80Ba39N9: the first Li/Ba subnitride.
AB  - The crystal structure of Li80Ba39N9, a new representative of alkali-alkaline
      earth metal subnitrides prepared from the metals and barium azide, was
      investigated based on single-crystal X-ray diffraction data. The compound has a
      novel crystal structure with a tetragonal unit cell, space group I(-)42m, a =
      16.0763(8) A, c = 32.267(2) A, Z = 2, and V = 8330.0(8) A3. The structure can be
      described in terms of subnitride clusters with internal ionic bonding and
      metallic bonding in the rest of the space. The compound contains a new cluster
      Li12Ba5N6 and polytetrahedral Li clusters based on centered Li13 icosahedra,
      which are typical for Li-rich intermetallic compounds.

PMID- 17173438
TI  - Synthesis, structure, and 15N NMR studies of paramagnetic lanthanide complexes
      obtained by reduction of dinitrogen.
AB  - The recently discovered LnZ3/M and LnZ2Z'/M methods of reduction (Ln =
      lanthanide; M = alkali metal; Z, Z' = monoanionic ligands that allow these
      combinations to generate "LnZ2" reactivity) have been applied to provide the
      first crystallographically characterized dinitrogen complexes of cerium,
      [C5Me5)2(THF)Ce]2(mu-eta2.eta2-N2) and [(C5Me4H)2(THF)Ce]2(mu-eta2.eta2-N2), so
      that the utility of 15N NMR spectroscopy with paramagnetic lanthanides could be
      determined. [(C5Me5)2(THF)Pr]2(mu-eta2.eta2-N2) and [(C5Me4H)2(THF)Pr]2(mu
      eta2.eta2-N2) were also synthesized, crystallographically characterized, and
      studied by 15N NMR methods. The data were compared to those of [(C5Me5)2Sm]2(mu
      eta2.eta2-N2). [(C5Me5)2(THF)Ce]2(mu-eta2.eta2-N2) and [(C5Me5)2(THF)Pr]2(mu
      eta2.eta2-N2) are unlike their (C5Me4H)1- analogs in that the solvating THF
      molecules are cis rather than trans. Structural information on precursors,
      (C5Me4H)3Ce, (C5Me4H)3Pr, and the oxidation product [(C5Me5)2Ce]2(mu-O) is also
      presented.

PMID- 17173439
TI  - Modeling zinc enzyme inhibition with functional thiolate ligands.
AB  - The blocking of zinc enzymes by thiolate-containing inhibitors was modeled by
      treating TpPh,MeZn-OH with functional thiols. The latter were chosen such that
      they contain an additional donor function (COOH, COOR, NH2, NHR, OH) in a
      position favorable for chelation. Of them, mercapto carboxylic acid esters were
      incorporated as thiolates. The corresponding mercapto carboxylic acids, however,
      used only their carboxylate function for coordination. Various mercapto amines,
      mercapto alcohols, and mercaptophenol were exclusively converted to thiolate
      ligands. The two modes of inhibitor attachment, terminal or chelating, were
      observed equally frequently. As a rule, they occur as alternatives for similar
      ligands. In case of 2-mercaptophenol they coexist in the crystalline state and in
      solution. Hydrogen bonding, both intra- and intermolecular, seems to be a
      decisive factor determining the inhibitor attachments. Its persistence in
      solution is underlined by the observation that TpPh,MeZn-hydroxythiophenolates
      are methylated about 2 orders of magnitude slower than TpPh,MeZn-SPh itself.

PMID- 17173440
TI  - F/Cl-exchange on AlCl(3)-pyridine adducts: synthesis and characterization of
      trans-difluoro-tetrakis-pyridine-aluminum-chloride, [AlF2(Py)4]+Cl-.
AB  - Whereas liquid CCl3F reacts with solid AlCl3 exothermically under chlorine
      fluorine-exchange already above -20 degrees C, no reaction takes place between
      CCl3F and the pyridine complexes of AlCl3 (AlCl3.Py, AlCl3.2Py, or AlCl3.3Py) up
      to 100 degrees C. The desired chlorine by fluorine substitution on the monomer
      AlCl3-pyridine adducts occurs, however, easily using Me3SiF as fluorinating
      agent. By reacting AlCl3.3Py with Me3SiF (even up to 10-fold stoichiometric
      excess) in pyridine as a solvent, only two of the three Cl atoms can be
      substituted by fluorine, leading in good yield to the new "mixed aluminum
      halide", AlF2Cl.4Py. Actually, it represents the first example of a stable solid
      donor-acceptor adduct of an aluminum-III halide with two different halogens of
      defined stoichiometry. It was characterized by multinuclear solid-state NMR (27Al
      and 19F), IR spectroscopy, as well as single-crystal structure analysis. The new
      compound has an ionic solid-state structure with helical trans-octahedral
      [(Py)4AlF2]+ cations and isolated Cl- anions. The comparison of its 27Al MAS
      solid-state NMR spectra with those of a compound bearing the analogous
      [(Py)4AlCl2]+ cation reveals an extreme increase in the quadrupolar coupling
      constants, from 0.24 MHz in case of the chlorine cation to about 16 MHz in case
      of the new [(Py)4AlF2]+ cation.

PMID- 17173441
TI  - Radical salts of bis(ethylenediseleno)tetrathiafulvalene with paramagnetic
      tris(oxalato)metalate anions.
AB  - The synthesis, crystal structure, and physical characterization of five new
      radical salts formed by the organic donor bis(ethylenediseleno)tetrathiafulvalene
      (BEST) and the paramagnetic tris(oxalato)metalate anions [M(C2O4)3]3- (M = FeIII
      and CrIII) are reported. The salts isolated are (BEST)4[M(C2O4)3].PhCOOH.H2O with
      MIII = Cr (1) or Fe (2) (crystal data: 1, triclinic, space group P(-)1 with a =
      14.0999(4) A, b = 15.3464(4) A, c =19.5000(4) A, alpha = 76.711(5) degrees, beta
      = 71.688(5) degrees, gamma = 88.545(5) degrees, V = 3893.5(2) A3, and Z = 2; 2,
      triclinic, space group P(-)1 with a = 14.0326(3) A, b =15.1981(4) A, c
      =19.4106(4) A, alpha = 76.739(5) degrees, beta = 71.938(5) degrees, gamma =
      88.845(5) degrees, V = 3824.9(2) A3, and Z = 2), (BEST)4[M(C2O4)3].1.5H2O with
      MIII = Cr (3) or Fe (4) (crystal data: 3, monoclinic, space group C2/m with a =
      33.7480(10) A, b =12.3151(7) A, c = 8.8218(5) A, beta = 99.674(5) degrees, V =
      3614.3(3) A3, and Z = 2; 4, monoclinic, space group C2/m with a = 33.659(6) A, b
      =12.248(2) A, c = 8.759(2) A, beta = 99.74(3) degrees, V = 3558.9(12) A3, and Z =
      2), and (BEST)9[Fe(C2O4)3]2.7H2O (5) (crystal data: triclinic, space group P(-)1
      with a =12.6993(3) A, b =18.7564(4) A, c = 18.7675(4) A, alpha = 75.649(5)
      degrees, beta = 107.178(5) degrees, gamma = 79.527(5) degrees, V = 3977.5(3) A3,
      and Z = 1). The structures of all these salts consist of alternating layers of
      the organic donors and tris(oxalato)metalate anions. In 1 and 2 the anionic
      layers contain also benzoic acid molecules H-bonded to the terminal oxygen atoms
      of the anions. In all salts the organic layers adopt beta-type packings. Along
      the parallel stacks the donors form dimers in 3 and 4, trimers in 5, and
      tetramers in 1 and 2. All the compounds are paramagnetic semiconductors with high
      room-temperature conductivities and magnetic susceptibilities dominated by the Fe
      or Cr-containing anions.

PMID- 17173442
TI  - Modeling the mononuclear, dinuclear, and trinuclear copper(I) reaction centers of
      copper proteins using pyridylalkylamine ligands connected to 1,3,5
      triethylbenzene spacer.
AB  - The structure and O2-reactivity of copper(I) complexes supported by novel
      ligands, Pye2 (1,3,5-triethyl-2,4-bis((N-benzyl-N-(2-(pyridin-2-yl)ethyl)
      )aminomethyl)benzene), Pye3 (1,3,5-triethyl-2,4,6-tris((N-benzyl-N-(2-(pyridin-2
      yl)ethyl))aminomethyl)benzene), MePym2 (1,3,5-triethyl-2,4-bis((N-benzyl-N-(6
      methylpyridin-2-ylmethyl))aminomethyl)benzene), and MePym3 (1,3,5-triethyl-2,4,6
      tris((N-benzyl-N-(6-methylpyridin-2-ylmethyl))aminomethyl)benzene) have been
      examined. The ligands are designed to construct mono-, di-, and trinuclear
      copper(I) complexes by connecting two or three pyridylalkylamine metal-binding
      sites to a 1,3,5-triethylbenzene spacer. Thus, the reaction of the ligands with
      [CuI(CH3CN)4]X (X = PF6, CF3SO3) or CuICl gave the expected mononuclear copper(I)
      complexes [CuI(Pye2)(CF3SO3)] (1) and [CuI(Pye3)](CF3SO3) (2), dinuclear
      copper(I) complex [CuI2(MePym2)(Cl)]CuICl2 (3), and trinuclear copper(I) complex
      [CuI3(MePym3)(CH3CN)3](CF3SO3)3 (4), the structures of which were determined by X
      ray crystallographic analysis. The mononuclear copper(I) complexes, 1 and 2,
      exhibit a distorted three-coordinate T-shape structure and a trigonal planar
      structure, respectively, which are very close to the coordination geometry of the
      CuA site of PHM (peptidylglycine alpha-hydroxylating monooxygenase) and the CuB
      site of CcO (cytochrome c oxidase). Notably, 1 and 2 showed a significantly high
      oxidation potential (990 mV vs SCE), thus showing virtually no reactivity toward
      O2. On the other hand, the metal centers of the dinuclear and trinuclear
      copper(I) complexes, 3 and 4, exhibit a distorted trigonal planar geometry and a
      trigonal pyramidal geometry, respectively. In contrast to the mononuclear
      copper(I) complexes, these dinuclear and trinuclear copper(I) complexes reacted
      with O2 to induce an aromatic ligand hydroxylation reaction involving an NIH
      shift of one of the ethyl substituents on the benzene spacer. The NIH-shift of
      the alkyl substituent on the aromatic ring is strong evidence of the
      electrophilic aromatic substitution mechanism, although the active oxygen
      intermediate could not be directly detected during the course of the reaction.
      The biological relevance of the copper(I) complexes is also discussed on the
      basis of structure and O2-reactivity.

PMID- 17173443
TI  - Biologically relevant phosphoranes: synthesis and structural characterization of
      glucofuranose-derived phosphoranes with penta- and hexacoordination at
      phosphorus.
AB  - Carbohydrate-based phosphoranes were synthesized by reacting the appropriate
      diphenol with phosphorus trichloride followed by the addition of chloralose to
      form 1 and by the addition of isopropylidene-D-glucofuranose to form 2 and 3.
      Phosphorane 4 was obtained by reacting 1,2-O-isopropylidene-alpha-D
      glucofuranosyl-3,5,6-phosphite (13) with a diphenol. For the synthesis of 5-9,
      the appropriate phosphite was reacted with isopropylidene-glucofuranose. X-ray
      analyses of 1-9 were carried out successfully. Hexacoordinated structures
      resulted via oxygen donor action at phosphorus in the cases of phosphoranes 1-3
      and via sulfur donor action for phosphoranes 4-6. Trigonal bipyramidal structures
      formed for 7-9 with the carbohydrate components occupying axial-equatorial sites.
      The eight-membered ring of the diphenol moiety with weak or no donor groups in 7
      9 occupied diequatorial sites of the trigonal bipyramid. Solution NMR data are in
      agreement with the assigned solid-state structures. Isomerism between penta- and
      hexacoordination is present in solution for 7. The isomerism observed for 7 and
      our previous study showing a rapid exchange process that reorients the
      carbohydrate component of the trigonal bipyramidal phosphorane suggest that these
      biophosphoranes may serve as models for active sites of phosphoryl-transfer
      enzymes. At an active site, this type of pseudorotational behavior provides a
      mechanism that could bring another active site residue into play and account for
      a means by which some phosphoryl-transfer enzymes express promiscuous behavior.

PMID- 17173444
TI  - Manganese carbonyl nitrosyls: comparison with isoelectronic iron carbonyl
      derivatives.
AB  - The manganese carbonyl nitrosyls Mn(NO)(CO)4, Mn2(NO)2(CO)n (n = 7, 6, 5, 4), and
      Mn3(NO)3(CO)9 have been studied by density functional theory (DFT) using the
      B3LYP and BP86 methods for comparison of their predicted structures with those of
      isoelectronic iron carbonyl derivatives. DFT predicts a trigonal bipyramidal
      structure for Mn(NO)(CO)4 with an equatorial NO group very close to the
      experimental structure. The predicted lowest energy structure for Mn2(NO)2(CO)7
      has two bridging NO groups in contrast to the known structure of the
      isoelectronic Fe2(CO)9, which has three bridging CO groups. The structures for
      the unsaturated binuclear Mn2(NO)2(CO)n (n = 6, 5, 4) derivatives are similar to
      those of the corresponding binuclear iron carbonyls Fe2(CO)n+2 derivatives but
      always with a preference of bridging NO groups over bridging CO groups. The
      trinuclear Mn3(NO)3(CO)9 is predicted to have a structure analogous to the known
      structure for Fe3(CO)12 but with two bridging NO groups rather than two bridging
      CO groups across one of the metal-metal edges of the M3 triangle. The dark red
      solid photolysis product of Mn(NO)(CO)4 characterized by its nu(CO) and nu(NO)
      frequencies approximately 45 years ago is suggested by these DFT studies not to
      be the originally assumed Mn2(NO)2(CO)7 analogous to Fe2(CO)9. Instead, this
      photolysis product appears to be Mn2(NO)2(CO)5 with a Mn(triple bond)Mn formal
      triple bond analogous to (eta5-C5H5)2V2(CO)5 obtained from the photolysis of
      (eta5-C5H5)V(CO)4.

PMID- 17173445
TI  - Mixed-metal cluster chemistry. 29. Core expansion and ligand-driven metal
      exchange at group 6-iridium clusters.
AB  - Reactions of the tetrahedral clusters MoIr3(mu-CO)3(CO)8(eta-L) (L = C5HMe4,
      C5Me5) with the carbonylmetalate anions [Mo(CO)3(eta-L)]- afford the trigonal
      bipyramidal clusters Mo2Ir3(mu3-H)(mu-CO)2(CO)9(eta-L)2 (L = C5HMe4 (3c), 74%; L
      = C5Me5 (3d), 55%) in which the group 6 metal atoms occupy the apexes; reaction
      of the cyclopentadienylmolybdenum-containing analogues or their
      cyclopentadienyltungsten-containing homologues failed to afford analogous
      products. Reactions of MIr3(mu-CO)3(CO)8(eta-C5H5) (M = Mo, W) with [M(CO)3(eta
      L)]- (L = C5HMe4, C5Me5) afford the core-expanded heteroapex clusters M2Ir3(mu3
      H)(mu-CO)2(CO)9(eta-C5H5)(eta-L) (M = Mo, L = C5HMe4 (5c), 9%, L = C5Me5 (5d),
      4%; M = W, L = C5Me5 (6d), 5%) in low yield, together with the homoapex clusters
      M2Ir3(mu3-H)(mu-CO)2(CO)9(eta-L)2 (M = Mo, L = C5HMe4 (3c), 81%, L = C5Me5 (3d),
      60%; M = W, L = C5Me5 (4d), 5%) in much higher yield for the Mo-containing
      examples. The identities of clusters 3c,d, 4d, and 5c,d have been confirmed by
      single-crystal X-ray diffraction studies, with the same disposition of ligands
      about the trigonal bipyramidal cluster cores being observed in each case, a
      ligand arrangement that has been examined by complementary density functional
      theory studies. While cluster 5d is accessible as above, no reaction is observed
      from MoIr3(mu-CO)3(CO)8(eta-C5Me5) and [M(CO)3(eta-C5H5)]-. Treating MoIr3(mu
      CO)3(CO)8(eta-C5H5) with 1 equiv of [M(CO)3(eta-C5Me5)]- affords 5d as the major
      product, a further 1 equiv affording some MoIr3(mu-CO)3(CO)8(eta-C5Me5) and a
      third 1 equiv giving a good yield of 3d. This is consistent with reaction
      proceeding by apex fragment addition, followed by apex fragment elimination, and
      finally a further apex fragment addition, the homometallic incoming apexes being
      distinguished from the departing vertices by their highly methylated
      cyclopentadienyl ligands. Spectroscopic data suggest that the electron density at
      these disparate-metal-containing cluster cores is tunable by progressive
      (conceptual) cyclopentadienyl alkylation.

PMID- 17173446
TI  - Probing crystal structures and transformation reactions of ammonium molybdates by
      14N MAS NMR spectroscopy.
AB  - The unique high-resolution feature offered by 14N magic-angle spinning (MAS) NMR
      spectroscopy of ammonium ions has been used to characterize the crystal
      structures of various ammonium molybdates by their 14N quadrupole coupling
      parameters, i.e., CQ, the quadrupole coupling constant, and etaQ, the asymmetry
      parameter. Two polymorphs of diammonium monomolybdate, (NH4)2MoO4, recently
      structurally characterized by single-crystal X-ray diffraction (XRD) and named
      mS60 and mP60, show distinct but different 14N MAS NMR spectra from each of which
      two sets of characteristic 14N CQ and etaQ values have been obtained. Similarly,
      the well-characterized ammonium polymolybdates (NH4)2Mo2O7, (NH4)6Mo7O24.4H2O,
      and (NH4)6Mo8O27.4H2O also give rise to distinct and characteristic 14N MAS NMR
      spectra. In particular, it is noted that simulation of the experimental
      (NH4)6Mo7O24.4H2O spectrum requires an iterative fit with six independent NH4+
      sites. For the slow spinning frequencies employed (nu(r) = 1500-3000 Hz), all 14N
      MAS NMR spectra of the ammonium molybdates in this study are fingerprints of
      their identity. These different 14N MAS NMR fingerprints are shown to be an
      efficient tool in qualitative and quantitative assessment of the decomposition of
      (NH4)2MoO4 in humid air. Finally, by a combination of the 14N and 95Mo MAS NMR
      experiments performed here, it has become clear that a recent report of the 95Mo
      MAS spectra and data for the mS60 and mP60 polymorphs of (NH4)2MoO4 are erroneous
      because the sample examined had decomposed to (NH4)2Mo2O7.

PMID- 17173447
TI  - Phenylazo-pyridine and phenylazo-pyrazole chlorido ruthenium(II) arene complexes:
      arene loss, aquation, and cancer cell cytotoxicity.
AB  - Ru(II) eta6-arene complexes containing p-cymene (p-cym), tetrahydronaphthalene
      (thn), benzene (bz), or biphenyl (bip), as the arene, phenylazopyridine
      derivatives (C5H4NN:NC6H5R; R = H (azpy), OH (azpy-OH), NMe2 (azpy-NMe2)) or a
      phenylazopyrazole derivative (NHC3H2NN:NC6H5NMe2 (azpyz-NMe2)) as N,N-chelating
      ligands and chloride as a ligand have been synthesized (1-16). The complexes are
      all intensely colored due to metal-to-ligand charge-transfer Ru 4d6-pi* and
      intraligand pi -->pi* transitions (eta = 5000-63 700 M-1 cm-1) occurring in the
      visible region. In the crystal structures of [(eta6-p-cym)Ru(azpy)Cl]PF6 (1),
      [(eta6-p-cym)Ru(azpy-NMe2)Cl]PF6 (5), and [(eta6-bip)Ru(azpy)Cl]PF6 (4), the
      relatively long Ru-N(azo) and Ru-(arene-centroid) distances suggest that
      phenylazopyridine and arene ligands can act as competitive pi-acceptors toward
      Ru(II) 4d6 electrons. The pKa* values of the pyridine nitrogens of the ligands
      are low (azpy 2.47, azpy-OH 3.06 and azpy-NMe2 4.60), suggesting that they are
      weak sigma-donors. This, together with their pi-acceptor behavior, serves to
      increase the positive charge on ruthenium, and together with the pi-acidic eta6
      arene, partially accounts for the slow decomposition of the complexes via
      hydrolysis and/or arene loss (t(1/2) = 9-21 h for azopyridine complexes, 310 K).
      The pKa* of the coordinated water in [(eta6-p-cym)Ru(azpyz-NMe2)OH2]2+ (13A) is
      4.60, consistent with the increased acidity of the ruthenium center upon
      coordination to the azo ligand. None of the azpy complexes were cytotoxic toward
      A2780 human ovarian or A549 human lung cancer cells, but several of the azpy
      NMe2, azpy-OH, and azpyz-NMe2 complexes were active (IC50 values 18-88 microM).

PMID- 17173448
TI  - Mononuclear Ni(III) complexes [NiIII(L)(P(C6H3-3-SiMe3-2-S)3)]0/1- (L = thiolate,
      selenolate, CH2CN, Cl, PPh3): relevance to the nickel site of [NiFe]
      hydrogenases.
AB  - The stable mononuclear Ni(III)-thiolate complexes [NiIII(L)(P(C6H3-3-SiMe3-2
      S)3)]- (L = SePh (2), Cl (3), SEt (4), 2-S-C4H3S (5), CH2CN (7)) were isolated
      and characterized by UV-vis, EPR, IR, SQUID, CV, 1H NMR, and single-crystal X-ray
      diffraction. The increased basicity (electronic density) of the nickel center of
      complexes [NiIII(L)(P(C6H3-3-SiMe3-2-S)3)]- modulated by the monodentate ligand L
      and the substituted groups of the phenylthiolate rings promotes the stability and
      reactivity. In contrast to the irreversible reduction at -1.17 V (vs
      Cp2Fe/Cp2Fe+) for complex 3, the cyclic voltammograms of complexes
      [NiIII(SePh)(P(o-C6H4S)3)]-, 2, 4, and 7 display reversible NiIII/II redox
      processes with E(1/2) = -1.20, -1.26, -1.32, and -1.34 V (vs Cp2Fe/Cp2Fe+),
      respectively. Compared to complex 2 containing a phenylselenolate-coordinated
      ligand, complex 4 with a stronger electron-donating ethylthiolate coordinated to
      the Ni(III) promotes dechlorination of CH2Cl2 to yield complex 3 (kobs = (6.01 +/
      0.03) x 10-4 s-1 for conversion of complex 4 into 3 vs kobs = (4.78 +/- 0.02) x
      10-5 s-1 for conversion of complex 2 into 3). Interestingly, addition of CH3CN
      into complex 3 in the presence of sodium hydride yielded the stable Ni(III)
      cyanomethanide complex 7 with a NiIII-CH2CN bond distance of 2.037(3) A. The
      NiIII-SEt bond length of 2.273(1) A in complex 4 is at the upper end of the 2.12
      2.28 A range for the NiIII-S bond lengths of the oxidized-form [NiFe]
      hydrogenases. In contrast to the inertness of complexes 3 and 7 under CO
      atmosphere, carbon monoxide triggers the reductive elimination of the monodentate
      chalcogenolate ligand of complexes 2, 4, and 5 to produce the trigonal
      bipyramidal complex [NiII(CO)(P(C6H3-3-SiMe3-2-S)3]- (6).

PMID- 17173449
TI  - Crystal absorption spectra in the region of 4f-4f and 4f-5d excitations in Tm2+
      doped CsCaCl3, CsCaBr3, and CsCaI3.
AB  - Low-temperature absorption spectra of single crystals of Tm2+-doped CsCaCl3,
      CsCaBr3, and CsCaI3 in the spectral range from 8700 to 47000 cm-1 are presented.
      Weak sharp-line 4f-4f absorptions around 8800 cm-1 are essentially independent of
      the nature of the halide. More-intense broad absorptions cover the region between
      12000 and 47000 cm-1. They are assigned to 4f-5d excitations and interpreted in
      terms of a simple qualitative picture taking into account the most important
      interactions. As a result of two counterbalancing effects, the onsets of the 4f
      5d spectra are almost coincident in the three materials: The blue-shift of about
      3000 cm-1 between chloride and iodide resulting from the decreasing crystal field
      splitting of 5d is roughly balanced by the red-shift resulting from the reduced
      energy gap between the average energy of the 4f13 and the 4f125d1 electron
      configurations. The absorption helps the understanding of the most unusual light
      emission properties of these materials.

PMID- 17173450
TI  - Luminescent hydrido-carbonyl clusters of rhenium containing bridging 1,2-diazine
      ligands.
AB  - The reaction of the electronically unsaturated (56 valence electrons, ve)
      tetrahedral cluster [Re4(mu3-H)4(CO)12] (1) with pyridazine (pydz) gives as the
      main initial product the tetranuclear cluster [Re4(mu-H)4(mu-pydz)(pydz)2(CO)12]
      (2a), with 64 ve and four hydrogen-bridged metal-metal interactions, with a
      spiked-triangle geometry. One of the three pydz ligands bridges, in a cis
      configuration, the cluster edge opposite to the vertex bearing the spike, as
      indicated by the X-ray single-crystal analysis. This species slowly decomposes,
      affording the dinuclear unsaturated (32 ve) complex [Re2(mu-H)2(mu-pydz)(CO)6]
      (3a) and two isomers of the tetranuclear cluster [Re4(mu-H)4(mu-pydz)2(CO)12] (64
      ve), sharing an unusual square cluster geometry and differing in the trans
      (major, 85%, 4a) or cis (4a') configuration of the bridging pydz ligands. The
      structures of 3a and 4a have been ascertained by X-ray analysis, while the
      characterization of 4a' was hampered by its instability (slowly transforming into
      3a in THF solution). Both the dimer and the square cluster 4a are also formed
      directly (and quickly) from 1, being present in solution since the beginning of
      the reaction. Cluster 4a is the main final reaction product. The reaction with
      phthalazine follows a similar course, with some differences in the relative
      amount of the final products 3b and 4b. Most of the novel complexes are able to
      emit light in solution at room temperature, and photophysical measurements were
      performed in CH2Cl2 solution on the main stable reaction products (i.e., the
      dinuclear species 3a and 3b and the trans square clusters 4a and 4b). The
      emission was in the range of 580-645 nm, from MLCT excited states, with lifetimes
      on the order of a hundred nanoseconds (50-473 ns). The quantum yields were 1
      order of magnitude higher for the squares (1.7 and 1.3% for 4a and 4b,
      respectively, in CH2Cl2) than for the dinuclear complexes ( approximately 0.1%).
      In the case of 4a, a blue shift and an increase of the emission intensity were
      observed upon decreasing the solvent polarity.

PMID- 17173451
TI  - Phosphorescent platinum(II) complexes derived from multifunctional chromophores:
      synthesis, structures, photophysics, and electroluminescence.
AB  - The synthesis and structural, photophysical, electrochemical, and
      electroluminescent properties of a novel class of trifunctional Pt(II)
      cyclometalated complexes are reported in which the hole-transporting
      triarylamine, electron-transporting oxadiazole, and electroluminescent metal
      components are integrated into a single molecule. These neutral metal chelates
      display good thermal stability (>250 degrees C under N2) and morphological
      stability. All of them exhibit intense ligand-centered fluorescence and
      phosphorescence in fluid solutions at room temperature, but the emission spectra
      become largely dominated by triplet emission bands in CH2Cl2 glass at 77 K.
      Substituents with different electronic properties were introduced into the
      bipolar cyclometalating ligands to fine-tune the absorption and emissive
      characteristics of the compounds, and the results were correlated with
      theoretical calculations using density functional theory. A comparison of the
      photophysics and electrochemistry of our multifunctional systems to those only
      derived from each of the constituent components was also made and discussed.
      These Pt complexes can be vacuum-sublimed and applied as emissive dopants for the
      fabrication of vapor-deposited electrophosphorescent organic light-emitting
      devices (OLEDs), which generally exhibit good device performance with
      efficiencies up to 3.6%, 11.0 cd A-1, and 5.8 lm W-1. While the
      electroluminescence energy resembles that recorded in fluid solutions for these
      Pt emitters, these monochromatic OLEDs can emit tunable colors by varying the
      aryl ring substituents and the level of doping. Saliently, single dopant white
      light electroluminescence, triggered by the simultaneous
      fluorescence/phosphorescence emission of the metal complexes and a variation of
      applied driving voltages, has also been realized based on some of these
      multifunctional complexes with peak electrophosphorescence efficiencies of 6.8 cd
      A-1 and 2.6%.

PMID- 17173452
TI  - Magnetic structure and magnetic properties of synthetic lindgrenite,
      Cu3(OH)2(MoO4)2.
AB  - Synthetic Cu3(OH)2(MoO4)2 consists of Cu3(OH)2 brucite ribbons of edge-sharing
      copper octahedra connected by MoO4 into a 3D network as in the mineral,
      lindgrenite, for all temperatures between 1.5 and 300 K. Each ribbon consists of
      a triangular connection between two different types of copper atom (Cu(1) and 2
      Cu(2)) via mu3-OH. The MoO4 acts both as one- and three-atom bridges to connect
      six Cu atoms belonging to three adjacent ribbons. The magnetic properties are
      consistent with those of ferrimagnetic chains, and the resulting moment of each
      chain is parallel below the long-range magnetic ordering at 13 K. The Curie
      constant is 0.468(1) emu K mol-1 of Cu; the Weiss temperature is -14.2(2) K, and
      the saturation magnetization at 2 K in 50 kOe is 0.41 N muB mol-1 of Cu. Analyses
      of the neutron powder diffraction reveal an ordered magnetic state where the
      moment of Cu(1) is antiparallel to those of the two Cu(2); all of them point
      along the a axis without any sign of geometrical frustration. Any degeneracy that
      may be present because of the triangular topology of the Cu atoms (s = 1/2)
      appears to be lifted by the distortion from an ideal equilateral geometry of the
      triangle. The entropy, estimated from the heat capacity measurements, attains 50%
      of the total of 17.7 J K-1 mol-1, close to that expected for three Cu atoms (3R
      ln 2), up to the long range ordering temperature, and the remaining is associated
      with the low dimensionality of the material.

PMID- 17173453
TI  - High-pressure synthesis and structure determination of K6(SeO4)(SeO5), the first
      potassium orthoselenate(VI).
AB  - We report on the first synthesis of a potassium orthoselenate(VI),
      K6(SeO4)(SeO5), and the structure determination from synchrotron powder
      diffraction data. The title compound crystallizes in the tetragonal space group
      P41212 with a = 8.1259(1) A, c = 17.4953(2) A, V = 1155.21(2) A3, and Z = 4.
      Selenium displays two different complex anions, tetrahedral SeO42- and trigonal
      bipyramidal SeO54-. When the formula is reduced to A3B, the spatial arrangement
      of the constituting building units can be derived from the Li3Bi type of
      structure.

PMID- 17173454
TI  - Spectroscopic and ab initio characterization of the [ReH9]2- ion.
AB  - The dynamics and bonding of the hydrido complex Ba[ReH9], containing the D3h face
      capped trigonal prismatic [ReH9]2- ion, have been investigated by vibrational
      spectroscopy and density functional theory (DFT). The combination of infrared,
      Raman, and inelastic neutron-scattering (INS) spectroscopies has enabled
      observation of all the modes of the [ReH9]2- ion for the first time. We
      demonstrate that calculations of the isolated [ReH9]2- ion are unable to
      reproduce the INS spectrum and that the complete unit cell must be considered
      with periodic DFT to have reliable results. This is shown to be a consequence of
      the long-range Coulomb potential present. Analysis of the electronic structure
      shows that the bonding between the rhenium and the hydrogen is largely covalent.
      There is a small degree of covalency between the prism hydrides and the barium.
      The counterion is crucial to the stability of the materials; hence, variation of
      it potentially offers a method to fine-tune the properties of the material.

PMID- 17173455
TI  - Isostructural bisdithiazolyl and bisthiaselenazolyl radicals: trends in bandwidth
      and conductivity.
AB  - Reaction of N-alkylated pyridine-bridged bisdithiazolylium cations [1]+ (R1 =Me,
      Et; R2 =Ph) with selenium dioxide in acetic acid provides a one-step high-yield
      synthetic route to bisthiaselenazolylium cations [2]+ (R1 = Me, Et; R2 = Ph). The
      corresponding radicals 1 and 2 can be prepared by chemical or electrochemical
      reduction of the cations. Structural analysis of the radicals has been achieved
      by a combination of single-crystal and powder X-ray diffraction methods. While
      the two sulfur radicals 1 adopt different space groups (P3(1)21 for R1 = Me and
      P(-)1 for R1 = Et), the two selenium radicals 2 (space groups P3(1)21 for R1 = Me
      and P3(2)21 for R1 =Et) are isostructural with each other and also with 1 (R1 =
      Me, R2 = Ph). Variable-temperature magnetic measurements on all four compounds
      confirm that they are undimerized S = 1/2 systems, with varying degrees of weak
      intermolecular antiferromagnetic coupling. Variable-temperature electrical
      conductivity measurements on the two selenium radicals provide conductivities
      sigma(300 K) = 7.4 x 10-6 (R1 = Et) and 3.3 x 10-5 S cm-1 (R1 = Me), with
      activation energies, E(act), of 0.32 (R1 = Et) and 0.29 eV (R1 = Me). The
      differences in conductivity within the isostructural series is interpreted in
      terms of their relative solid-state bandwidths, as estimated from Extended Huckel
      band-structure calculations.

PMID- 17173456
TI  - Heterometallic dithiolene complexes formed by stepwise displacement of
      cyclopentadienyl ligands from nickelocene with CpMo(S2C2Ph2)2.
AB  - The dithiolene ligand transfer reaction between Ni(S2C2Ph2)2 (1) and CpMo(CO)3Cl
      (2; Cp = eta-C5H5) affords the neutral paramagnetic molybdenum bis(dithiolene)
      complex CpM(S2C2Ph2)2 (3), which has been structurally characterized. As found in
      other d1 complexes of this type, one dithiolene ligand is planar while the other
      is significantly folded toward the Cp ligand. An unexpected second product of the
      reaction is the unusual trinuclear species Ni[Mo(S2C2Ph2)2Cp]2 (4), which in the
      solid state contains three different dithiolene bonding modes (terminal,
      bridging, and semi-bridging) in the same molecule. Complex 4 can also be
      synthesized by displacement of the diene ligands in Ni(cod)2 with 2 equiv of 3.
      In contrast, the reaction of nickelocene with 3 proceeds by displacement of the
      Cp ligands in a stepwise manner to give initially the dinuclear species NiMo(mu
      S2C2Ph2)2Cp2 5, which then reacts further with 3 to produce 4.

PMID- 17173457
TI  - Copper(II) complexes of salen analogues with two differently substituted (push
      pull) salicylaldehyde moieties. A study on the modulation of electronic asymmetry
      and nonlinear optical properties.
AB  - This paper presents some copper(II) complexes of salen analogues in which the two
      salicylaldehyde moieties carry different (electron donor, D, and acceptor, A)
      substituents in position 5, producing a push-pull charge asymmetry. The X-ray
      structures of some compounds show the presence of pairs of stacked molecules with
      head-to-tail intermolecular associations. The geometries of all complexes have
      been optimized through density functional theory (DFT) studies, which have shown
      that a major influence on the coordination bond lengths is given by the presence
      of the electron acceptor NO2 group. Such an influence operates mainly on the Cu
      phenolato bonds: elongation of the Cu-O distance of the 5-nitrosalicylaldehyde
      moiety, with a concomitant decrease of the other Cu-O distance; the Cu-N bonds
      are less affected. The D groups have only a minor influence. The nonlinear
      optical responses, microgBetavec, of some molecules have been determined by EFISH
      measurements, and the Beta-vec values have been obtained using the DFT-calculated
      microg values because solubility problems hampered the experimental measurements
      of microg of some derivatives; the former, however, have been found to be in
      agreement with the experimental values that could be obtained. Deconvolution of
      the absorption bands in the near-UV region has allowed recognition of the charge
      transfer (CT) transition, assigned to a ligand-to-metal CT (LMCT) by time
      dependent DFT computations; we have then used the solvatochromism of this
      transition to obtain Beta0 and BetaCT values using the two-state model. These
      values were compared with those obtained by computational studies, which have
      also allowed evaluation of the influence of the substituents on the directions of
      microg and Betatot.

PMID- 17173458
TI  - Dinuclear iridium(III) complexes consisting of back-to-back tpy-(ph)n-tpy
      bridging ligands (n = 0, 1, or 2) and terminal cyclometallating tridentate N-C-N
      ligands.
AB  - Three dinuclear iridium(III) complexes consisting of a conjugated bis-tpy type
      bridging ligand and cyclometallating capping tridentate ligands of the 1,3-di-2
      pyridylbenzene family have been prepared (tpy, 2,2',6',2' '-terpyridine). The two
      tpy units of the bridge are connected via their back-positions (4') either
      directly or with a p-phenylene or p-biphenylene spacer. The synthesis relies on
      the reaction between the dinuclear [Ir(dpb)Cl2]2 complex (dpb-H =1,3-dipyridyl
      4,6-dimethylbenzene) and the corresponding bis-tpy ligand. Electrochemical
      measurements afford metal-centered oxidation and ligand-centered reduction
      potentials; from the oxidation steps, no evidence is obtained for a strong
      coupling between the two iridium(III) subunits of the dinuclear species. For all
      complexes, ground-state absorption data in the 380 nm to visible region show a
      trend which is consistent with the presence of charge-transfer (CT) transitions
      involving different degrees of electronic delocalization at the bridging ligands.
      (dpb)Ir(tpy-tpy)Ir(dpb)4+ exhibits an appreciable luminescence at room
      temperature (phi = 3.0 x 10(-3); tau = 3.3 ns), whereas no emission from the
      other binuclear complexes is detected. All binuclear complexes luminesce at 77 K,
      and a metal-to-ligand CT nature for (dpb)Ir(tpy-tpy)Ir(dpb)4+ is suggested,
      whereas a ligand-centered (LC) emission is proposed for (dpb)Ir(tpy-(ph)2
      tpy)Ir(dpb)4+ on the basis of the comparison with the phosphorescence properties
      of the free bridging ligand, tpy-(ph)2-tpy. Transient absorbance experiments at
      room temperature afford the absorption spectra and lifetimes of the non-emissive
      excited states. For (dpb)Ir(tpy-ph-tpy)Ir(dpb)4+ and (dpb)Ir(tpy-(ph)2
      tpy)Ir(dpb)4+, the spectra exhibit a broad profile peaking around 780 nm, quite
      intense in the case of (dpb)Ir(tpy-(ph)2-tpy)Ir(dpb)4+, and lifetimes of 160 and
      440 ps, respectively.

PMID- 17173459
TI  - Janus scorpionates: supramolecular tectons for the directed assembly of hard-soft
      alkali metallopolymer chains.
AB  - A new scorpionate ligand [HB(mtda)3-] containing mercaptothiadiazolyl (mtda)
      heterocyclic rings with both hard nitrogen donors and soft sulfur donors has been
      prepared. This new ligand, the Janus scorpionate, is a hybrid of a
      tris(pyrazolyl)borate and a tris(mercaptoimidazolyl)borate. The differential
      hard/soft character of the dissimilar donor groups in this bridging ligand was
      exploited for the controlled solid-state organization of homometallic and
      heterometallic alkali metal coordination polymers. Remarkably, in the case of
      sodium, coordination polymers with both acentric (with NaS3N3H kernels) and
      centric (with alternating NaN6 and NaS6H2 kernels) chains are found in the same
      crystal (where the centricity is defined by the relative orientations of the B-H
      bonds of the ligands along the lattice). For the homometallic potassium congener,
      the larger cation size, compared to sodium, induced significant distortions and
      favored a polar arrangement of ligands in the resulting coordination polymer
      chain. An examination of the solid-state structure of the mixed alkali metal salt
      system revealed that synergistic binding of smaller sodium cations to the
      nitrogen portion and of the larger potassium cations to the sulfur portion of the
      ligand minimizes the ligand distortions relative to the homometallic coordination
      polymer counterparts, a design feature of the ligand that likely assists in
      thermodynamically driving the self-assembly of the heterometallic chains. The
      effect of alkali metal complexation on the solution properties of the ligand was
      studied by comparing NMR chemical shifts, B-H stretching frequencies, and
      electrochemical properties with those of the noncoordinating tetrabutylammonium
      salt of the scorpionate. The similarity of these data regardless of cation
      indicates that the salts are likely dissociated in solution rather than
      maintaining their solid-state polymeric structures. This data is augmented by the
      ESI(+/-) mass spectral data for a series of mixed alkali metal
      tris(mercaptothiadiazolyl)borates that also indicate that dissociation occurs in
      solution.

PMID- 17173460
TI  - Guanidinate-stabilized monomeric hafnium amide complexes as promising precursors
      for MOCVD of HfO2.
AB  - Novel guanidinato complexes of hafnium [Hf{eta2-(iPrN)2CNR2}2(NR2)2] (R2 = Et2,
      1; Et, Me, 2; Me2, 3), synthesized by insertion reactions of N,N'
      diisopropylcarbodiimide into the M-N bonds of homologous hafnium amide complexes
      1-3 and {[mu2-NC(NMe2)2][NC(NMe2)2]2HfCl}2 (4) using a salt metathesis reaction,
      are reported. Single-crystal X-ray diffraction analysis revealed that compounds 1
      3 were monomers, while compound 4 was found to be a dimer. The observed fluxional
      behavior of compounds 1-3 was studied in detail using variable-temperature and
      two-dimensional NMR techniques. The thermal characteristics of compounds 1-3 seem
      promising for HfO2 thin films by vapor deposition techniques. Metal-organic
      chemical vapor deposition experiments with compound 2 as the precursor resulted
      in smooth, uniform, and stoichiometric HfO2 thin films at relatively low
      deposition temperatures. The basic properties of HfO2 thin films were
      characterized in some detail.

PMID- 17173461
TI  - Extended dipolar nonlinear optical chromophores based on trans-bis[1,2
      phenylenebis(dimethylarsine)]chlororuthenium(II) centers.
AB  - Four new complex salts trans[RuIICl(pdma)2LA][PF6]n [pdma = 1,2
      phenylenebis(dimethylarsine); LA = 1,4-bis[E-2-(4-pyridyl)ethenyl]benzene (bpvb),
      n = 1, 1; LA = N-methyl-1,4-bis(E-2-(4-pyridyl)ethenyl)benzene (Mebpvb+), n = 2,
      2; LA = N-phenyl-1,4-bis(E-2-(4-pyridyl)ethenyl)benzene (Phbpvb+), n = 2, 3; LA =
      N-(2-pyrimidyl)-1,4-bis(E-2-(4-pyridyl)ethenyl)benzene (Pymbpvb+), n = 2, 4] have
      been prepared. The electronic absorption spectra of 1-4 display intense, visible
      metal-to-ligand charge-transfer (MLCT) bands, with lambda(max) values in the
      range 432-474 nm in acetonitrile. Intense intraligand charge-transfer (ILCT)
      bands due to LA are also observed, with lambda(max) values in the range 350-416
      nm. Cyclic voltammetric studies in acetonitrile reveal reversible RuIII/II waves
      with E(1/2) values of ca. 1.05 V vs Ag/AgCl, together with LA-based reduction
      processes that are irreversible with the exception of 1. Salts 1-4 have been
      investigated by using Stark (electroabsorption) spectroscopy in butyronitrile
      glasses at 77 K. These studies have afforded dipole moment changes, Deltamu12,
      for the MLCT and ILCT transitions which have been used to calculate molecular
      static first hyperpolarizabilities, Beta0, according to the two-state equation
      Beta0 = 3Deltamu12(mu12)2/(Emax)2 (mu12 = transition dipole moment, Emax =
      MLCT/ILCT energy). In contrast with related RuII ammine complexes, replacement of
      a central E-ethylene bond with a 1,4-phenylene unit does not appear to be an
      especially effective strategy for combating the NLO transparency-efficiency
      tradeoff in these pdma complexes. Single-crystal X-ray studies with the complex
      salts 2 and 3 and also with the pro-ligand salt [Phbpvb+] PF6.0.5HPF6 show that
      these materials all adopt centrosymmetric packing structures.

PMID- 17173462
TI  - Layered lanthanide molybdate pillared by chiral [lambda-Mo2O4EDTA]2-.
AB  - Hydrothermal reactions of Na2[Mo2O4EDTA].5H2O and LnCl3.6H2O produce the chiral
      layered lanthanide molybdate oxides pillared by the chiral cluster ligand,
      [Ln(H2O)MoO4]2[lambda-Mo2O4EDTA] (Ln = Gd, 1; Eu, 2; Tb, 3; Y, 4). The
      tetradentate molybdate bridges Ln3+ to form a square grid structure, which is
      pillared by the chiral cluster ligand, [lambda-Mo2O4EDTA]2-, into a 3-D chiral
      framework structure. Strong VCD (vibrational circular dichroism) signals confirm
      the chirality of the bulk oxide materials. These bimetallic oxide materials are
      of highly thermal stability. The magnetic interactions between the Ln3+ ions in 1
      and 3 are weak antiferromagnetic.

PMID- 17173463
TI  - Concerning the electronic coupling of MoMo quadruple bonds linked by 4,4'
      azodibenzoate and comparison with t2g 6-Ru(II) centers by 4,4'
      azodiphenylcyanamido ligands.
AB  - From the reactions between Mo2(O2CtBu)4 and each of terephthalic acid and 4,4'
      azodibenzoic acid, the compounds [Mo2(O2CtBu)3]2(mu-O2CC6H4CO2) (1) and
      [Mo2(O2CtBu)3]2(mu-O2CC6H4N2C6H4CO2) (2) have been made and characterized by
      spectroscopic and electrochemical methods. Their electronic structures have been
      examined by computations employing density functional theory on model compounds
      where HCO2 substitutes for tBuCO2. On the basis of these studies, the two Mo2
      units are shown to be only weakly coupled and the mixed-valence ions 1+ and 2+ to
      be valence-trapped and Class II and I, respectively, on the Robin-Day
      classification scheme for mixed-valence compounds. These results are compared to
      t2g6-Ru centers linked by 1,4-dicyanamidobenzene and azo-4,4'-diphenylcyanamido
      bridges for which the mixed-valence ions [Ru-bridge-Ru]5+ have been previously
      classified as fully delocalized, Class III [Crutchley et al. Inorg. Chem. 2001,
      40, 1189; Inorg. Chem. 2004, 43, 1770], and on the basis of results described
      herein, it is proposed that the latter complex ion is more likely a mixed-valence
      organic radical where the bridge is oxidized and not the Ru(2+) centers.

PMID- 17173464
TI  - DNA cleavage on photoexposure at the d-d band in ternary copper(II) complexes
      using red-light laser.
AB  - Ternary copper(II) complexes [Cu(L1)B](ClO4) (1, 2) and [Cu(L2)B](ClO4) (3, 4),
      where HL1 and HL2 are tridentate NSO- and ONO-donor Schiff bases and B is a
      heterocyclic base, viz. dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 1 and 3) or
      dipyrido[3,2-a:2',3'-c]phenazine (dppz, 2 and 4), were prepared and their DNA
      binding and photoinduced DNA cleavage activity studied. Complex 1, structurally
      characterized by single-crystal X-ray crystallography, shows an axially elongated
      square-pyramidal (4 + 1) coordination geometry in which the monoanionic L1 binds
      at the equatorial plane. The NN-donor dpq ligand exhibits an axial-equatorial
      binding mode. The complexes display good binding propensity to calf thymus DNA,
      giving a relative order 2 (NSO-dppz) > 4 (ONO-dppz) > 1 (NSO-dpq) > 3 (ONO-dpq).
      They cleave supercoiled pUC19 DNA to its nicked circular form when treated with 3
      mercaptopropionic acid (MPA) by formation of hydroxyl radicals as the cleavage
      active species under dark reaction conditions. The photoinduced DNA cleavage
      activity of the complexes was investigated using UV radiation of 365 nm and red
      light of 633, 647.1, and 676.4 nm (CW He-Ne and Ar-Kr mixed gas ion laser
      sources) in the absence of MPA. Complexes 1 and 2, having photoactive NSO-donor
      Schiff base and dpq/dppz ligands, show dual photosensitizing effects involving
      both the photoactive ligands in the ternary structure with significantly better
      cleavage properties when compared to those of 3 and 4, having only photoactive
      dpq/dppz ligands. Involvement of singlet oxygen in the light-induced DNA cleavage
      reactions is proposed. A significant enhancement of the red-light-induced DNA
      cleavage activity is observed for the dpq and dppz complexes containing the
      sulfur ligand when compared to their earlier reported phen (1,10-phenanthroline)
      analogue. Enhancement of the cleavage activity on photoexposure at the d-d band
      indicates the occurrence of metal-assisted photosensitization processes involving
      the LMCT and d-d band in the ternary structure.

PMID- 17173465
TI  - Multireference ab initio calculations on reaction intermediates of the
      multicopper oxidases.
AB  - The multicopper oxidases (MCOs) couple the four-electron reduction of dioxygen to
      water with four one-electron oxidations of various substrates. Extensive
      spectroscopic studies have identified several intermediates in the MCO catalytic
      cycle, but they have not been able to settle the structures of three of the
      intermediates, viz. the native intermediate (NI), the peroxy intermediate (PI),
      and the peroxy adduct (PA). The suggested structures have been further refined
      and characterized by quantum mechanical/molecular mechanical (QM/MM)
      calculations. In this paper, we try to establish a direct link between theory and
      experiment, by calculating spectroscopic parameters for these intermediates using
      multireference wave functions from the multistate CASPT2 and MRDDCI2 methods.
      Thereby, we have been able to reproduce low-spin ground states (S = 0 or S = 1/2)
      for all the MCO intermediates, as well as a low-lying (approximately 150 cm-1)
      doublet state and a doublet-quartet energy gap of approximately 780 cm-1 for the
      NI. Moreover, we reproduce the zero-field splitting (approximately 70 cm-1) of
      the ground 2E state in a D3 symmetric hydroxy-bridged trinuclear Cu(II) model of
      the NI and obtain a quantitatively correct quartet-doublet splitting (164 cm-1)
      for a mu3-oxo-bridged trinuclear Cu(II) cluster. All results support the
      suggestion that the NI has an O2- atom in the center of the trinuclear cluster,
      whereas both the PI and PA have an O22- ion in the center of the cluster, in
      agreement with the QM/MM results and spectroscopic measurements.

PMID- 17173468
TI  - Management of cutaneous dermatomyositis: current therapeutic options.
AB  - Dermatomyositis is an idiopathic inflammatory myopathy with characteristic
      cutaneous manifestations and proximal muscle weakness. Patients with this
      condition frequently require treatment for muscular, systemic, and cutaneous
      involvement; however, the cutaneous symptoms often cause significant morbidity
      and frustration to patients. The skin lesions of dermatomyositis often persist or
      recur after treatment of myositis, and there are subsets of patients who have
      significant cutaneous disease with little or no muscle involvement. Only
      anecdotal evidence is available for cutaneous treatment, and the approach to
      therapy is guided by disease severity and refractoriness. First-line therapy for
      localized disease begins with topical agents such as antipruritics and/or
      corticosteroids, while widespread disease often requires initial systemic
      therapy. Antimalarials are generally used for significant skin disease, followed
      by other anti-inflammatory agents, systemic corticosteroids, corticosteroid
      sparing immunosuppressants and, recently, biologics and intravenous
      immunoglobulin. While there is a recognized absence of randomized prospective
      clinical trials examining the optimal monotherapy and combination treatment for
      the cutaneous manifestations of dermatomyositis, we have tried to provide a
      review of the literature and a systematic approach to dealing with these often
      refractory and debilitating symptoms.

PMID- 17173466
TI  - Thermodynamics of pyridine coordination in 1,4-phenylene bridged bimetallic (Pd,
      Pt) complexes containing two N,C,N' motifs, 1,4-M2-[C6(CH2NR2)4-2,3,5,6].
AB  - The thermodynamics of pyridine coordination in 1,4-phenylene-bridged binuclear
      palladium and platinum organometallic complexes [1,4-(MOTf)2-&{C6(CH2NR2)4
      2,3,5,6}] (11, M =Pd, Pt; R =CH3, C2H5, R2 = -(CH2)5-) are measured by 1H NMR in
      DMSO-d6. The coordination of substituted pyridines by bimetallic complexes 11 or
      12 in DMSO is found to proceed via two effectively independent metalligand
      binding events, and the association constants for pyridine coordination and rate
      constants for pyridine exchange are nearly identical to those measured previously
      on monometallic analogs. A linear free energy relationship between the
      association constant for pyridine coordination and the inductive Hammett constant
      of the pyridine substituent is observed, and the sensitivity (rho = -1.7 to -2.1)
      in DMSO depends only slightly on metal (Pd vs Pt) and spectator ligand (pincer
      dialkylamine vs triarylphosphine). The association constant for a particular
      pyridine ligand, however, varies by roughly 3 orders of magnitude across the
      series of metal complexes. The effective independence of the two coordination
      sites and the range of available thermodynamic and kinetic behaviors of the
      coordination guide the use of these versatile building blocks in
      metallosupramolecular applications.

PMID- 17173469
TI  - Efficacy and safety of hyaluronic acid in the management of acute wounds.
AB  - INTRODUCTION: Hyaluronic acid (hyaluronan) is a key component of the
      extracellular matrix and is known to be involved in several mechanisms of the
      wound healing process. It has been shown to improve and accelerate the healing
      process of chronic wounds. This open-label study investigated whether application
      of hyaluronic acid could also improve the healing progression of acute wounds.
      METHODS: Forty-three patients with acute wounds, including trauma wounds,
      surgical sutures, burns, and dermabrasions, were included in the study.
      Hyaluronic acid (ialuset) was applied either as a cream or as a dressing, and the
      progression and quality of healing were evaluated at each application for a
      maximum of nine applications. RESULTS: The mean surface area of the wounds
      decreased from 556 mm(2) at baseline to 169 mm(2) by the sixth evaluation, an
      average reduction of 70% in the surface area of the wounds. Complete healing
      occurred in 56% of cases by the sixth application. Little or no fibrin was
      observed in 91% of cases, and 84% of wounds showed little or no exudate. Both
      formulations of hyaluronic acid were well tolerated and were rated highly by
      nurses and patients for ease of use and treatment satisfaction. CONCLUSION:
      Interpretation of the results of this open-label study is limited by the lack of
      a standard wound dressing as a comparator and by the varying types of wounds
      selected for inclusion. Nevertheless, the results of this study indicate that
      hyaluronic acid provides good healing of acute wounds and is well accepted by
      both patients and nurses.

PMID- 17173470
TI  - Intravenous immunoglobulin use in patients with toxic epidermal necrolysis and
      Stevens-Johnson syndrome.
AB  - Intravenous immunoglobulin (IVIg) has been proposed as a treatment for toxic
      epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). A comprehensive
      search of the literature was conducted to examine the efficacy and safety of IVIg
      in TEN and SJS patients. Seventeen relevant articles (14 TEN, 3 SJS) were
      identified. Only three of the TEN studies and one of the SJS studies were
      prospective; retrospective studies were the most common study design published.
      Information regarding disease severity, IVIg use, response, and hospitalization
      were recorded and cumulated. Aggregate level statistics were calculated. The
      average IVIg doses used were 0.8 +/- 0.4 g/kg/day for a mean duration of 4.0 +/-
      1.0 days in TEN patients and 0.8 +/- 0.2 g/kg/day for 3.4 +/- 1.0 days in SJS
      patients. The clinical experience of IVIg use in TEN and SJS patients was
      positive in most cases. However, more studies need to be conducted to confirm the
      benefit of IVIg use in patients with TEN or SJS.

PMID- 17173472
TI  - Cutaneous sarcoidosis: the "great imitator": etiopathogenesis, morphology,
      differential diagnosis, and clinical management.
AB  - Sarcoidosis is a multisystem disease that can involve almost any organ system.
      The underlying cause of the disease remains unknown. Immunopathologically and
      histologically, cutaneous sarcoidosis is characterized by a macrophage/T helper-1
      cell-mediated, non-caseating, granulomatous inflammation process. An imbalance
      between proinflammatory and anti-inflammatory cytokines plays an important role
      in the development of cutaneous granulomas. Recognition of cutaneous sarcoidosis
      lesions is very important because they provide a visible clue to the diagnosis
      and are an easily accessible source of tissue for histologic examination. Because
      skin lesions of patients with the disease can exhibit many different
      morphologies, cutaneous sarcoidosis is known as one of the "great imitators" in
      dermatology. Specific manifestations can include patches (sometimes
      hypopigmented), papules, scar sarcoidosis, ulcers, ichthyosis, and alopecia. The
      treatment of cutaneous sarcoidosis is often frustrating because some of the skin
      lesions may be refractory to treatment or may recur following successful
      treatment. Systemic and topical corticosteroids are the most effective treatments
      for cutaneous sarcoidosis. This article focuses on the dermatologic aspects of
      sarcoidosis and includes a review of the most recent literature, which includes
      new data on the diagnosis, differential diagnosis, pathogenesis, and treatment of
      the disease.

PMID- 17173471
TI  - Review of literature on amicrobial pustulosis of the folds associated with
      autoimmune disorders.
AB  - Amicrobial pustulosis of the folds (APF) is characterized by relapsing, primary
      aseptic, pustular eruptions mainly affecting the cutaneous folds, scalp, and
      periorificial regions such as the mouth, external ear canal, and nostrils. APF is
      a rare condition that has previously been reported in 25 women exhibiting a wide
      spectrum of autoimmune abnormalities, particularly systemic lupus erythematosus.
      Histology of the skin lesions usually shows spongiform pustulation in the upper
      layer of the epidermis and a polymorphonuclear infiltrate in the dermis. APF must
      be differentiated from other noninfectious pustular diseases such as subcorneal
      pustulosis (Sneddon-Wilkinson disease) and pustular forms of psoriasis. APF
      should be included in the spectrum of reactive neutrophilic dermatoses, even
      though the exact pathomechanisms remain obscure. However, the striking female
      predominance may be of pathogenetic significance. Based on the small number of
      previously reported patients, the most effective therapy seems to be medium-dose
      systemic corticosteroids.

PMID- 17173473
TI  - Absence of estrogen and progesterone receptors around the affected vessels of
      angioma serpiginosum: case report.
AB  - Angioma serpiginosum is a disorder of dilated superficial dermal capillaries. The
      disease is considered by some authors to be a consequence of increasing levels of
      estrogens. We present a case of angioma serpiginosum in a 46-year-old White
      woman. The lesions consisting of red-purple puncta were grouped as vaguely
      annular and angular patches with serpiginous borders, located on the right side
      of the neck, the right side of the abdomen, and on the left arm. Histopathologic
      examination revealed clusters of dilated capillaries in the dermal papillae,
      without endothelial proliferation. Periodic acid-Schiff (PAS) stain-positive
      deposits were noted around the affected blood vessels. However,
      immunohistochemical analysis revealed the absence of estrogen and progesterone
      receptors within the involved blood vessels. Hormonal assays were also normal.
      Our observations suggest that a hormonal stimulus probably plays no role in the
      pathogenesis of angioma serpiginosum. The significance of PAS-positive deposits
      as a diagnostic marker for angioma serpiginosum needs further confirmation.

PMID- 17173474
TI  - Scalp ulcer as first sign of cholangiocarcinoma.
AB  - Metastases from distant primary tumors are rarely the first indicators of cancer.
      However, cutaneous metastases are not uncommon in cases of internal malignancy.
      This article describes the case of a 65-year-old man with cutaneous metastasis of
      cholangiocarcinoma who presented with a scalp ulcer as the only initial sign.
      This is only the third reported case of cholangiocarcinoma with distant cutaneous
      metastasis.

PMID- 17173475
TI  - Dermal dendrocyte ballooning.

PMID- 17173477
TI  - Toxic epidermal necrolysis in oncologic patients.

PMID- 17173478
TI  - Computational reconstruction of iron- and manganese-responsive transcriptional
      networks in alpha-proteobacteria.
AB  - We used comparative genomics to investigate the distribution of conserved DNA
      binding motifs in the regulatory regions of genes involved in iron and manganese
      homeostasis in alpha-proteobacteria. Combined with other computational
      approaches, this allowed us to reconstruct the metal regulatory network in more
      than three dozen species with available genome sequences. We identified several
      classes of cis-acting regulatory DNA motifs (Irr-boxes or ICEs, RirA-boxes, Iron
      Rhodo-boxes, Fur-alpha-boxes, Mur-box or MRS, MntR-box, and IscR-boxes) in
      regulatory regions of various genes involved in iron and manganese uptake, Fe-S
      and heme biosynthesis, iron storage, and usage. Despite the different nature of
      the iron regulons in selected lineages of alpha-proteobacteria, the overall
      regulatory network is consistent with, and confirmed by, many experimental
      observations. This study expands the range of genes involved in iron homeostasis
      and demonstrates considerable interconnection between iron-responsive regulatory
      systems. The detailed comparative and phylogenetic analyses of the regulatory
      systems allowed us to propose a theory about the possible evolution of Fe and Mn
      regulons in alpha-proteobacteria. The main evolutionary event likely occurred in
      the common ancestor of the Rhizobiales and Rhodobacterales, where the Fur protein
      switched to regulating manganese transporters (and hence Fur had become Mur). In
      these lineages, the role of global iron homeostasis was taken by RirA and Irr,
      two transcriptional regulators that act by sensing the physiological consequence
      of the metal availability rather than its concentration per se, and thus provide
      for more flexible regulation.

PMID- 17173479
TI  - Insight into the structure of amyloid fibrils from the analysis of globular
      proteins.
AB  - The conversion from soluble states into cross-beta fibrillar aggregates is a
      property shared by many different proteins and peptides and was hence conjectured
      to be a generic feature of polypeptide chains. Increasing evidence is now
      accumulating that such fibrillar assemblies are generally characterized by a
      parallel in-register alignment of beta-strands contributed by distinct protein
      molecules. Here we assume a universal mechanism is responsible for beta-structure
      formation and deduce sequence-specific interaction energies between pairs of
      protein fragments from a statistical analysis of the native folds of globular
      proteins. The derived fragment-fragment interaction was implemented within a
      novel algorithm, prediction of amyloid structure aggregation (PASTA), to
      investigate the role of sequence heterogeneity in driving specific aggregation
      into ordered self-propagating cross-beta structures. The algorithm predicts that
      the parallel in-register arrangement of sequence portions that participate in the
      fibril cross-beta core is favoured in most cases. However, the antiparallel
      arrangement is correctly discriminated when present in fibrils formed by short
      peptides. The predictions of the most aggregation-prone portions of initially
      unfolded polypeptide chains are also in excellent agreement with available
      experimental observations. These results corroborate the recent hypothesis that
      the amyloid structure is stabilised by the same physicochemical determinants as
      those operating in folded proteins. They also suggest that side chain-side chain
      interaction across neighbouring beta-strands is a key determinant of amyloid
      fibril formation and of their self-propagating ability.

PMID- 17173480
TI  - NFAT5 regulates HIV-1 in primary monocytes via a highly conserved long terminal
      repeat site.
AB  - To replicate, HIV-1 capitalizes on endogenous cellular activation pathways
      resulting in recruitment of key host transcription factors to its viral enhancer.
      RNA interference has been a powerful tool for blocking key checkpoints in HIV-1
      entry into cells. Here we apply RNA interference to HIV-1 transcription in
      primary macrophages, a major reservoir of the virus, and specifically target the
      transcription factor NFAT5 (nuclear factor of activated T cells 5), which is the
      most evolutionarily divergent NFAT protein. By molecularly cloning and sequencing
      isolates from multiple viral subtypes, and performing DNase I footprinting,
      electrophoretic mobility shift, and promoter mutagenesis transfection assays, we
      demonstrate that NFAT5 functionally interacts with a specific enhancer binding
      site conserved in HIV-1, HIV-2, and multiple simian immunodeficiency viruses.
      Using small interfering RNA to ablate expression of endogenous NFAT5 protein, we
      show that the replication of three major HIV-1 viral subtypes (B, C, and E) is
      dependent upon NFAT5 in human primary differentiated macrophages. Our results
      define a novel host factor-viral enhancer interaction that reveals a new
      regulatory role for NFAT5 and defines a functional DNA motif conserved across HIV
      1 subtypes and representative simian immunodeficiency viruses. Inhibition of the
      NFAT5-LTR interaction may thus present a novel therapeutic target to suppress HIV
      1 replication and progression of AIDS.

PMID- 17173481
TI  - Dynamics of the cellular metabolome during human cytomegalovirus infection.
AB  - Viral replication requires energy and macromolecular precursors derived from the
      metabolic network of the host cell. Despite this reliance, the effect of viral
      infection on host cell metabolic composition remains poorly understood. Here we
      applied liquid chromatography-tandem mass spectrometry to measure the levels of
      63 different intracellular metabolites at multiple times after human
      cytomegalovirus (HCMV) infection of human fibroblasts. Parallel microarray
      analysis provided complementary data on transcriptional regulation of metabolic
      pathways. As the infection progressed, the levels of metabolites involved in
      glycolysis, the citric acid cycle, and pyrimidine nucleotide biosynthesis
      markedly increased. HCMV-induced transcriptional upregulation of specific
      glycolytic and citric acid cycle enzymes mirrored the increases in metabolite
      levels. The peak levels of numerous metabolites during infection far exceeded
      those observed during normal fibroblast growth or quiescence, demonstrating that
      HCMV markedly disrupts cellular metabolic homeostasis and institutes its own
      specific metabolic program.

PMID- 17173482
TI  - Soft sweeps III: the signature of positive selection from recurrent mutation.
AB  - Polymorphism data can be used to identify loci at which a beneficial allele has
      recently gone to fixation, given that an accurate description of the signature of
      selection is available. In the classical model that is used, a favored allele
      derives from a single mutational origin. This ignores the fact that beneficial
      alleles can enter a population recurrently by mutation during the selective
      phase. In this study, we present a combination of analytical and simulation
      results to demonstrate the effect of adaptation from recurrent mutation on
      summary statistics for polymorphism data from a linked neutral locus. We also
      analyze the power of standard neutrality tests based on the frequency spectrum or
      on linkage disequilibrium (LD) under this scenario. For recurrent beneficial
      mutation at biologically realistic rates, we find substantial deviations from the
      classical pattern of a selective sweep from a single new mutation. Deviations
      from neutrality in the level of polymorphism and in the frequency spectrum are
      much less pronounced than in the classical sweep pattern. In contrast, for levels
      of LD, the signature is even stronger if recurrent beneficial mutation plays a
      role. We suggest a variant of existing LD tests that increases their power to
      detect this signature.

PMID- 17173483
TI  - Adaptive stress response in segmental progeria resembles long-lived dwarfism and
      calorie restriction in mice.
AB  - How congenital defects causing genome instability can result in the pleiotropic
      symptoms reminiscent of aging but in a segmental and accelerated fashion remains
      largely unknown. Most segmental progerias are associated with accelerated
      fibroblast senescence, suggesting that cellular senescence is a likely
      contributing mechanism. Contrary to expectations, neither accelerated senescence
      nor acute oxidative stress hypersensitivity was detected in primary fibroblast or
      erythroblast cultures from multiple progeroid mouse models for defects in the
      nucleotide excision DNA repair pathway, which share premature aging features
      including postnatal growth retardation, cerebellar ataxia, and death before
      weaning. Instead, we report a prominent phenotypic overlap with long-lived
      dwarfism and calorie restriction during postnatal development (2 wk of age),
      including reduced size, reduced body temperature, hypoglycemia, and perturbation
      of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These
      symptoms were also present at 2 wk of age in a novel progeroid nucleotide
      excision repair-deficient mouse model (XPD(G602D/R722W)/XPA(-/-)) that survived
      weaning with high penetrance. However, despite persistent cachectic dwarfism,
      blood glucose and serum insulin-like growth factor 1 levels returned to normal by
      10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These
      data strongly suggest changes in energy metabolism as part of an adaptive
      response during the stressful period of postnatal growth. Interestingly, a
      similar perturbation of the postnatal growth axis was not detected in another
      progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/-)
      mouse. Specific (but not all) types of genome instability may thus engage a
      conserved response to stress that evolved to cope with environmental pressures
      such as food shortage.

PMID- 17173484
TI  - The complete genome sequence and comparative genome analysis of the high
      pathogenicity Yersinia enterocolitica strain 8081.
AB  - The human enteropathogen, Yersinia enterocolitica, is a significant link in the
      range of Yersinia pathologies extending from mild gastroenteritis to bubonic
      plague. Comparison at the genomic level is a key step in our understanding of the
      genetic basis for this pathogenicity spectrum. Here we report the genome of Y.
      enterocolitica strain 8081 (serotype 0:8; biotype 1B) and extensive microarray
      data relating to the genetic diversity of the Y. enterocolitica species. Our
      analysis reveals that the genome of Y. enterocolitica strain 8081 is a patchwork
      of horizontally acquired genetic loci, including a plasticity zone of 199 kb
      containing an extraordinarily high density of virulence genes. Microarray
      analysis has provided insights into species-specific Y. enterocolitica gene
      functions and the intraspecies differences between the high, low, and
      nonpathogenic Y. enterocolitica biotypes. Through comparative genome sequence
      analysis we provide new information on the evolution of the Yersinia. We identify
      numerous loci that represent ancestral clusters of genes potentially important in
      enteric survival and pathogenesis, which have been lost or are in the process of
      being lost, in the other sequenced Yersinia lineages. Our analysis also
      highlights large metabolic operons in Y. enterocolitica that are absent in the
      related enteropathogen, Yersinia pseudotuberculosis, indicating major differences
      in niche and nutrients used within the mammalian gut. These include clusters
      directing, the production of hydrogenases, tetrathionate respiration, cobalamin
      synthesis, and propanediol utilisation. Along with ancestral gene clusters, the
      genome of Y. enterocolitica has revealed species-specific and enteropathogen
      specific loci. This has provided important insights into the pathology of this
      bacterium and, more broadly, into the evolution of the genus. Moreover, wider
      investigations looking at the patterns of gene loss and gain in the Yersinia have
      highlighted common themes in the genome evolution of other human enteropathogens.

PMID- 17173486
TI  - Impact of statin copayments on adherence and medical care utilization and
      expenditures.
AB  - OBJECTIVE: To examine the effects of statin cost-sharing (ie, copayments,
      coinsurance) on adherence to statin medications and the impact of adherence on
      healthcare utilization and spending. STUDY DESIGN: Retrospective, observational
      study of statin users receiving health benefits or supplemental coverage from
      employer-sponsored health plans. METHODS: Medical and pharmacy claims were
      selected from the Medstat MarketScan database for patients who were continuously
      enrolled from 2000 through 2003. Two-stage residual inclusion models were
      estimated. The first stage modeled adherence to statins, which was derived from
      the medication possession ratio, and represented the percentage of days on
      therapy in an 18-month time frame, July 2001 through December 2002. In the second
      stage, generalized linear models were used to estimate 2003 utilization and
      expenditures. Separate estimates were produced for new statin users (n = 24 113)
      and continuing statin users (n = 93 253). RESULTS: Lower statin copayments were
      associated with higher levels of statin adherence. In percentage terms, when
      holding all other variables at their mean value, a $10 increase in copayment
      resulted in a 1.8 percentage point reduction in the probability of adherence for
      new users and a 3 percentage point reduction in the probability of adherence for
      continuing users. For continuing users adherent to statins, total costs did not
      change, but fewer negative events (emergency department visits, hospitalizations,
      and coronary heart disease-related hospitalizations) occurred. CONCLUSIONS:
      Policy makers and plan managers should consider interventions that improve
      adherence to statins, such as lower copayments.

PMID- 17173487
TI  - The effect of cost sharing on employees with diabetes.

PMID- 17173489
TI  - Innovations to preserve quality and contain cost.

PMID- 17173485
TI  - Global mapping of transposon location.
AB  - Transposable genetic elements are ubiquitous, yet their presence or absence at
      any given position within a genome can vary between individual cells, tissues, or
      strains. Transposable elements have profound impacts on host genomes by altering
      gene expression, assisting in genomic rearrangements, causing insertional
      mutations, and serving as sources of phenotypic variation. Characterizing a
      genome's full complement of transposons requires whole genome sequencing,
      precluding simple studies of the impact of transposition on interindividual
      variation. Here, we describe a global mapping approach for identifying transposon
      locations in any genome, using a combination of transposon-specific DNA
      extraction and microarray-based comparative hybridization analysis. We use this
      approach to map the repertoire of endogenous transposons in different laboratory
      strains of Saccharomyces cerevisiae and demonstrate that transposons are a source
      of extensive genomic variation. We also apply this method to mapping bacterial
      transposon insertion sites in a yeast genomic library. This unique whole genome
      view of transposon location will facilitate our exploration of transposon
      dynamics, as well as defining bases for individual differences and adaptive
      potential.

PMID- 17173488
TI  - Impact of a musculoskeletal disability management program on medical costs and
      productivity in a large manufacturing company.
AB  - OBJECTIVE: To evaluate a program to reduce musculoskeletal disability-related
      absenteeism at a North American manufacturing facility. STUDY DESIGN: Staged
      communication and educational interventions targeting physicians to improve care
      of musculoskeletal conditions and reduce related absenteeism. METHODS: The
      program was implemented in three 1-year stages. The first stage required
      physicians to complete assessment forms for employees claiming disability because
      of musculoskeletal injuries. The second stage added physician education programs
      focusing on current clinical guidelines. The third stage incorporated local
      physician education about the facility's onsite physical therapy program. Annual
      number of work-related injuries, days lost per injury and per scheduled full-time
      equivalent (FTE) employee, light-duty days per injury, average annual indemnity
      per FTE, indemnity per injury, medical costs per FTE, and medical costs per
      injury were examined to determine the program's effectiveness. RESULTS: Overall
      productivity improved by a mean of 12.5 days per injured employee. Mean days lost
      per work-related injury decreased from 35.1 to 27.6. Number of light-duty days
      increased from 6.1 to 11.1 per work-related injury. Mean annual indemnity per
      work-related injury decreased from $9327 to $4493; mean annual medical costs per
      work-related injury decreased from $4848 to $2679. The annual incidence of
      musculoskeletal injuries declined by up to 50%. CONCLUSIONS: This intervention
      was associated with reduced musculoskeletal disability-related absenteeism and
      increased productivity. The program reduced medical costs per work-related injury
      and improved the company's communications and relationship with local physicians.

PMID- 17173491
TI  - Engaging employees in health and wellness: the "Healthy Pfizer" program.

PMID- 17173490
TI  - Evaluation of the "Know Your Health" program for type 2 diabetes mellitus and
      hypertension in a large employer group.
AB  - OBJECTIVE: To evaluate the effect of an educational intervention program on
      clinical outcomes and on compliance with medical therapy in patients with type 2
      diabetes mellitus (DM), hypertension, or both. STUDY DESIGN: Six-month randomized
      unblinded study. METHODS: Three hundred fifty-two patients were screened, and 347
      were randomized to the intervention group (education through the Know Your Health
      [KYH] program [n = 174]) or to the control group (usual care [n = 173]).
      Evaluation of the effectiveness of the KYH program was based on the cohort of
      patients who were not at goal at baseline (124 in the intervention group and 115
      in the control group). The primary research interests were to assess patient
      acceptance of the KYH materials and to compare the clinical outcomes of the
      intervention group with those of the control group. RESULTS: After 6 months,
      significantly more patients in the intervention group than in the control group
      were at goal (44.2% vs 29.2%, P = .046). Among patients with hypertension,
      reductions in the mean diastolic blood pressure were significantly greater in the
      intervention group compared with the control group at month 6 (-6.7 vs -3.6 mm
      Hg, P = .04). The groups did not differ significantly on other primary end points
      (percentage of patients with DM who were at goal, change from baseline
      glycosylated hemoglobin level, and change in Morisky score). CONCLUSIONS:
      Participation in the KYH educational program during a 6-month period improved
      clinical outcomes in patients with type 2 DM or hypertension. The KYH materials
      were well received and were considered informative and easily comprehensible by
      patients who completed the program.

PMID- 17173492
TI  - Value-based insurance design: aligning incentives to bridge the divide between
      quality improvement and cost containment.
AB  - Rising costs and suboptimal clinical quality have spawned efforts to redesign
      healthcare benefit packages. Momentum has gathered behind 2 trends; the first,
      represented by disease management initiatives and pay-for-performance programs,
      focuses on the quality of care, and uses tools to manage patient health. The
      second trend, represented by increased patient cost sharing and consumer-driven
      health plans, focuses on the cost of care and uses financial incentives to alter
      patient and provider behavior. These 2 trends create a conflict for the patient
      in that disease management programs--designed to improve patient self-management-
      aim to enhance compliance with specific clinical interventions, while rising
      copayments create financial barriers that discourage the use of these recommended
      services. When patients are required to pay more for their healthcare, they buy
      less, even if the intervention is potentially lifesaving. Thus, the challenge for
      purchasers is to devise benefit packages that incorporate a range of features
      that complement each other in the effective and efficient delivery of care while
      explicitly avoiding the unwanted negative clinical effects associated with
      increased cost sharing.

PMID- 17173493
TI  - Placing a new technique into clinical practice.

PMID- 17173495
TI  - Hypertension, possible vascular protection and lercanidipine.
AB  - Systemic hypertension is a major global problem contributing to enormous disease
      burden, premature morbidity and mortality. A substantial majority of hypertensive
      patients require long-term drug therapy for appropriate blood pressure control.
      Although there are many classes of antihypertensive drugs for clinical use,
      calcium channel blockers (CCBs) have a special role in the management of
      hypertension owing to their well established safety and efficacy among the CCBs;
      the dihydropyridines (DHPs) are recognized for their predictable efficacy and
      dependability to achieve the recommended target goals of treatment. The older
      DHPs, such as nifedipine, felodipine and amlodipine, can cause bothersome side
      effects, such as ankle edema. The new-generation lipophilic DHP CCBs, such as
      lercanidipine, offer an advantage of less frequent occurrence of ankle edema.
      Furthermore, lercanidipine (in contrast to older DHPs) exerts favorable
      cardiorenal effects. Lercanidipine administered alone or in combination with
      other antihypertensive drugs represents a useful treatment option for efficient
      blood pressure control without causing significant adverse effects.

PMID- 17173496
TI  - Regulation of smooth muscle cells in development and vascular disease: current
      therapeutic strategies.
AB  - Vascular smooth muscle cells (SMCs) exhibit extensive phenotypic diversity and
      rapid growth during embryonic development, but maintain a quiescent,
      differentiated state in adult. The pathogenesis of vascular proliferative
      diseases involves the proliferation and migration of medial vascular SMCs into
      the vessel intima, possibly reinstating their embryonic gene expression programs.
      Multiple mitogenic stimuli induce vascular SMC proliferation through cell cycle
      progression. Therapeutic strategies targeting cell cycle progression and
      mitogenic stimuli have been developed and evaluated in animal models of
      atherosclerosis and vascular injury, and several clinical studies. Recent
      discoveries on the recruitment of vascular progenitor cells to the sites of
      vascular injury suggest new therapeutic potentials of progenitor cell-based
      therapies to accelerate re-endothelialization and prevent engraftment of SMC
      lineage progenitor cells. Owing to the complex and multifactorial nature of SMC
      regulation, combinatorial antiproliferative approaches are likely to be used in
      the future in order to achieve maximal efficacy and reduce toxicity.

PMID- 17173497
TI  - The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease.
AB  - Owing to the common coincidence of osteoporosis and vascular disease,
      pathophysiological links between both disorders have long been sought. The
      osteoprotegerin (OPG)/receptor activator of NF-kappaB (RANK)/receptor activator
      of NF-kappaB ligand (RANKL) cytokine network, a key regulatory system in bone
      homeostasis, has been implicated recently in vascular calcification, changes in
      matrix composition and diabetic macroangiopathy, aortic aneurysm development,
      heart failure and, most importantly, advanced atherosclerosis, plaque
      destabilization and manifestation of cardiovascular diseases. The concept of an
      active role of RANKL and OPG in vascular pathophysiology is intriguing and is
      gaining increasing support from both epidemiological and basic research. OPG
      serum level is considered to be a stable and reliable indicator of the overall
      activity of the OPG/RANK/RANKL axis and may find application as a biomarker of
      vascular risk and prognosis. RANKL in turn may be a suitable target for novel
      therapies. Pharmacological strategies for specific interference with the
      OPG/RANK/RANKL axis are currently being developed and evaluated in osteoporosis
      therapy.

PMID- 17173499
TI  - Ischemic mitral regurgitation: pathophysiology, diagnosis and surgical treatment.
AB  - Ischemic mitral valve regurgitation often complicates acute myocardial infarction
      and also represents a negative prognostic factor for long-term survival in
      patients undergoing surgical myocardial revascularization. While severe mitral
      regurgitation should always be corrected during a coronary artery bypass
      operation, the decision making is more difficult in patients with a mild-to
      moderate degree of regurgitation. Recent studies and experimental protocols have
      elucidated the pathophysiological mechanisms leading to mitral regurgitation with
      great interest in annular modifications and subvalvular alterations. These data
      suggest that new and integrated surgical approaches that address annuloplasty
      ring sizing, ring type selection and tethering phenomenon (i.e., chordal cutting,
      'edge-to-edge' technique and left-ventricular plasty techniques) are required for
      a safer and durable valve repair. Transthoracic and transesophageal
      echocardiography are useful in determining the etiology and the degree of mitral
      regurgitation, to assess mitral deformation and to measure indexes of global and
      regional left-ventricular remodeling. Stress echocardiography may unmask higher
      degrees of mitral regurgitation. More data are needed in order to confirm the
      promising and interesting preliminary experimental findings of magnetic resonance
      imaging in diagnosis and clinical evaluation of ischemic mitral regurgitation.

PMID- 17173498
TI  - ADAMTS13 and microvascular thrombosis.
AB  - Interaction between platelet and von Willebrand factor, a circulating adhesive
      glycoprotein, is essential for hemostasis under the high shear environments of
      arterioles and capillaries. If unregulated, this interaction may lead to
      unwarranted platelet thrombosis. ADAMTS13 (a disintegrin and metalloprotease with
      thrombospondin type 1 motif, number 13), a plasma zinc metalloprotease
      synthesized primarily in the stellate cells of the liver, cleaves shear stress
      activated von Willebrand factor, thereby preventing the occurrence of von
      Willebrand factor-platelet interaction in the circulation. A profound deficiency
      of ADAMTS13, due to genetic mutations or autoimmune inhibition, results in
      intravascular von Willebrand factor platelet aggregation and widespread
      microvascular thrombosis characteristic of thrombotic thrombocytopenic purpura.
      Cloning of ADAMTS13 and structure-function analyses of the enzyme are leading to
      exciting advances in the diagnosis and therapy of this hitherto mysterious
      disease.

PMID- 17173500
TI  - Endovascular versus open repair of ruptured abdominal aortic aneurysms.
AB  - Although major improvement has occurred to make elective repair of abdominal
      aortic aneurysms a safe procedure, the incidence of ruptured abdominal aortic
      aneurysms and mortality rates are still disappointing. Endovascular abdominal
      aortic aneurysm repair has produced quantum changes in aneurysm treatment. The
      successful application of the endovascular approach for the treatment of
      abdominal aortic aneurysms in the elective setting has prompted a strong interest
      regarding its possible use in dealing with the long-standing challenge of a
      ruptured abdominal aortic aneurysm. Since the first report, several centers have
      reported results and a wide spectrum of opinion regarding its application, with
      special consideration to logistical and practical barriers for appropriate
      utilization. The purpose of this article is to review all the available
      literature on the endovascular repair of ruptured abdominal aortic aneurysms and
      to analyze the most recent trends in their management, with special consideration
      given to comparing results of conventional and endovascular approaches.

PMID- 17173501
TI  - Microemboli in aortic valve replacement.
AB  - Microembolic signals (MES) can be detected in many recipients of mechanical
      aortic valve prostheses by transcranial Doppler ultrasound. The nature and
      etiology of these MES have remained unclear for a long time. The solid and
      gaseous nature of MES are discussed, as well as whether or not MES may reflect
      artifacts. Recently, the gaseous nature of these MES has been widely established.
      To understand the physics of bubble formation related to mechanical heart valve
      prostheses, it is necessary to discuss the different types of cavitation
      occurring at the prostheses and the conditions leading to the degassing of blood.
      We describe the history of transcranial Doppler ultrasound-techniques and the
      current techniques in the measurement of these signals. Furthermore, the possible
      clinical impact of MES, as well as strategies for the design of new prostheses
      and surgical alternatives to diminish their load are discussed.

PMID- 17173502
TI  - In search of a pediatric cardiac surgeon's 'Holy Grail': the ideal pulmonary
      conduit.
AB  - The limited lifespan of all currently available conduits leads to repeat
      operations and interventional procedures in many children. Each reoperation
      entails considerable risk to life, expenditure and compromised quality of life as
      the conduit degenerates. The ideal conduit should be available freely,
      inexpensive, require no anticoagulation, be resistant to infection, free from
      thromboembolism, have no gradients or regurgitation and have unlimited
      durability. This review explores various options as surgeons and researchers
      endeavor to develop the ideal conduit--which will fulfill all of the above
      mentioned criteria. Various currently available conduits are analyzed. Special
      emphasis is given to tissue-engineered valves and percutaneous valve
      implantations.

PMID- 17173503
TI  - Adiposopathy: how do diet, exercise and weight loss drug therapies improve
      metabolic disease in overweight patients?
AB  - An increase in bodyweight is generally associated with an increased risk of
      excessive fat-related metabolic diseases (EFRMD), including Type 2 diabetes
      mellitus, hypertension and dyslipidemia. However, not all patients who are
      overweight have EFRMD, and not all patients with EFRMD are significantly
      overweight. The adipocentric paradigm provides the basis for a unifying,
      pathophysiological process whereby fat gain in susceptible patients leads to fat
      dysfunction ('sick fat'), and wherein pathological abnormalities in fat function
      (adiposopathy) are more directly related to the onset of EFRMD than increases in
      fat mass (adiposity) alone. But just as worsening fat function worsens EFRMD,
      improved fat function improves EFRMD. Peroxisome proliferator-activated receptor
      gamma agonists increase the recruitment, proliferation and differentiation of
      preadipocytes ('healthy fat') and cause apoptosis of hypertrophic and
      dysfunctional (including visceral) adipocytes resulting in improved fat function
      and improved metabolic parameters associated with EFRMD. Weight loss
      interventions, such as a hypocaloric diet and physical exercise, in addition to
      agents such as orlistat, sibutramine and cannabinoid receptor antagonists, may
      have favorable effects upon fat storage (lipogenesis and fat distribution),
      nutrient metabolism (such as free fatty acids), favorable effects upon adipose
      tissue factors involved in metabolic processes and inflammation, and enhanced
      'cross-talk' with other major organ systems. In some cases, weight loss
      therapeutic agents may even affect metabolic parameters and adipocyte function
      independently of weight loss alone, suggesting that the benefit of these agents
      in improving EFRMD may go beyond their efficacy in weight reduction. This review
      describes how adiposopathy interventions may affect fat function, and thus
      improve EFRMD.

PMID- 17173504
TI  - Physical activity or fitness and the metabolic syndrome.
AB  - The metabolic syndrome is highly prevalent in populations around the world,
      regardless of the definition used. Physical inactivity and obesity are two of the
      major modifiable risk factors for the metabolic syndrome. Cross-sectional and
      prospective studies have generally found that levels of physical activity and
      fitness are inversely related to the prevalence of this syndrome. More recent
      research has also suggested that sedentary behaviors, such as excessive time
      spent watching television or using a computer, are significantly associated with
      an increased risk for this syndrome. Separate but complementary approaches that
      encourage increased participation in physical activity and discourage sedentary
      behaviors, both at the individual and population level, may prove useful in
      reducing the prevalence of this syndrome.

PMID- 17173505
TI  - Primary and secondary prevention of heart failure with statins.
AB  - Statins are effective in the prevention of coronary heart disease (CHD), a
      leading cause of heart failure (HF). Secondary analyses from 11 randomized
      clinical trials of patients with high-risk acute or stable coronary heart
      disease, but without HF, suggest that statins may prevent new-onset HF or HF
      related hospitalization. In persons with established HF, several cohort studies
      found an approximate 35% relative risk reduction in all-cause mortality. While
      ongoing randomized clinical trials will help to determine the efficacy of statins
      in persons with established HF, it is reasonable to consider this class of
      medications in patients with a history of cardiovascular disease, dyslipidemia or
      diabetes mellitus, and who have either developed, or who remain at risk of, HF.

PMID- 17173506
TI  - Genetic basis of hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) was the first cardiovascular disorder in which
      a genetic basis was identified. The disease is characterized by a marked
      thickening of the left ventricle and is the most common structural cause of
      sudden cardiac death in those aged under 35 years. HCM is primarily a disease of
      the sarcomere with over 250 mutations identified currently within 13 sarcomere
      related genes. At present, genetic screening is available for the genes shown to
      cause HCM most frequently, with a mutation pick-up rate of up to 60%. Current
      research is focused on the identification of additional causative genes and
      elucidation into signaling mechanisms involved in HCM pathogenesis, as well as
      investigation of modifying factors that can alter the clinical phenotype in HCM.
      The unifying goal of these studies is to improve our understanding of disease
      pathogenesis in HCM, thereby facilitating the process of new diagnostic and
      therapeutic approaches in patients, ultimately leading to disease prevention and
      possible curative treatment.

PMID- 17173507
TI  - Therapeutic options for patients with severe beta-thalassemia: the need for
      globin gene therapy.

PMID- 17173508
TI  - Completion of the railroad to Lhasa.

PMID- 17173512
TI  - Ataxia: an early indicator in high altitude cerebral edema.
AB  - Wu, Tianyi, Shouquan Ding, Jinliang Liu, Jianhou Jia, Ruichen Dai, Baozhu Liang,
      Jizhui Zhao, and Detang Qi. Ataxia: an early indicator in high altitude cerebral
      edema. High Alt. Med. Biol. 7:275-280, 2006.--As a result of industrial
      development in the western region of China, in 2001 the Chinese government
      decided to build Qinghai-Tibetan Railway. The new railroad stretches 1118 km from
      Golmud (2808 m) to Lhasa (3658 m), with more than three-quarter of the distance
      above 4000 m, through the Mt. Kun Lun and Tanggula ranges. From the beginning of
      the project on June, 29, 2001, to the end of the year of 2003, about 74,735
      construction workers worked in the harsh climate, in adverse circumstances and a
      low-barometric-pressure environment. The construction provided an opportunity for
      the investigation and study of acute mountain sickness (AMS), high altitude
      pulmonary edema (HAPE), and high altitude cerebral edema (HACE). These altitude
      illnesses were very common in the construction workers. From July 1, 2001, to
      October 31, 2003, the overall incidence of AMS, HAPE, and HACE in the total
      workers was approximately 45%-95%, 0.49%, and 0.26%, respectively. Altitude
      illnesses were studied at two hospitals near the construction site. One hospital
      is located on the Fenghuoshan (Mt. Wind-gap) at an altitude of 4779 m (PB 428
      torr), and the second hospital is situated in the Kekexili area at an altitude of
      4505 m (PB 440 torr). Kekexili is a sparsely populated zone because the weather
      conditions are very bad all year round. These two hospitals received patients
      from the construction sites, where workers were working at altitudes between 4464
      and 4905 m. A total of 8014 workers were treated at Fenghuoshan and 5488 were in
      Kekexili over the past 3 years. According to local guidance about proper medical
      care, workers ascending to high altitude should be examined physically, complete
      an AMS questionnaire, and be monitored for ataxia as an early warning sign of the
      impending, more serious aspects of HACE. The onset of HACE is frequently
      characterized by an ataxic gait, as reported since the middle of the 20th century
      (Gray et al., 1971; Wilson, 1973; Houston and Dickinson, 1975; Dickinson, 1979;
      Clarke, 1988; Hackett and Oelz, 1992; Hackett, 2002; Hackett and Roach, 2004).
      However, there are no detailed analyses of ataxia in HACE. This paper considers
      the relation between ataxia and HACE and its frequency, significance, and
      importance.

PMID- 17173513
TI  - No association between variants in the ACE and angiotensin II receptor 1 genes
      and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at
      4380 m.
AB  - Koehle, Michael S., Pei Wang, Jordan A. Guenette, and Jim L. Rupert. No
      association between variants in the ACE and angiotensin II receptor 1 genes and
      acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at
      4380 m. High Alt. Med. Biol. 7:281-289, 2006.--Acute mountain sickness (AMS)
      causes significant morbidity among visitors to altitude. The primary contributors
      to developing AMS are altitude and rate of ascent; however, the substantial
      variation in susceptibility between individuals has led a number of investigators
      to propose that there may be genetic predilection to the disease. The ACE I/D
      polymorphism has been shown to predict performance among elite mountaineers. This
      study compares genotype and allele frequencies at the ACE I/D locus, two other
      loci in the ACE gene, and one locus in the angiotensin-2 receptor gene between
      individuals who did, or did not, express signs of AMS while attending a high
      altitude religious festival in Nepal (4380 m). Subjects (80 males, 23 females)
      were recruited and genotyped. All subjects were Nepalese. Forty-four of the
      subjects had been diagnosed with AMS by physicians at a high altitude health
      camp; the rest were free from altitude illness. All subjects were genotyped at
      polymorphic loci in the genes encoding angiotensin converting enzyme (ACE) and
      angiotensin II receptor type 1 gene (AGTR1). The polymorphisms examined were two
      single nucleotide polymorphisms (SNPs) in ACE (ACE(A-240T), dbSNP rs4291; and
      ACE(A2350G), dbSNP rs4343), the intronic Alu insertion in ACE (ACE I/D), and the
      SNP ATR(A1166C), (dbSNP rs17231380) in AGTR1d. All polymorphisms in ACE were
      found to be in linkage disequilibrium. No significant associations were found
      between AMS incidence and any of the alleles, suggesting that variants at these
      loci do not contribute to susceptibility to AMS in this population.

PMID- 17173514
TI  - Acetazolamide improves cerebral oxygenation during exercise at high altitude.
AB  - Vuyk, Jaap, Jan Van Den Bos, Kees Terhell, Rene De Bos, Ad Vletter, Pierre Valk,
      Martie Van Beuzekom, Jack Van Kleef, and Albert Dahan. Acetazolamide improves
      cerebral oxygenation during exercise at high altitude. High Alt. Med. Biol. 7:290
      301, 2006.--Acute mountain sickness is thought to be triggered by cerebral
      hypoxemia and be prevented by acetazolamide (Actz). The effect of Actz on
      cerebral oxygenation at altitude remains unknown. In 16 members of the 2005 Dutch
      Cho Oyu (8201 m, Tibet) expedition, the influence of Actz and exercise (750 mg PO
      daily) on heart rate, peripheral and regional cerebral oxygen saturation (Sa(O(2)
      ) and rS(O(2) )), the Lake Louise score (LLS), and psychomotor function were
      studied at 0 m 14 days prior to the expedition, after arrival at 3700 m on day 3,
      after arrival at 5700 m on day 29, and again at 5700 m before the end of the
      expedition on day 51. After arrival at 3700 m, the LLS of the climbers taking
      Actz (n = 8) was significantly lower compared to those who did not take Actz (n =
      8): 0.75 +/- 1.0 versus 2.9 +/- 2.0, p < 0.05 (ANOVA). High LLSs were associated
      with low rS(O(2) ) values in rest and exercise (p < 0.01 and p < 0.001). With
      altitude, resting Sa(O(2) ) and resting rS(O(2) ) decreased significantly (p <
      0.001), irrespective of Actz use. Exercise at 3700 m and 5700 m reduced Sa(O(2) )
      and rS(O(2) ) even further compared to rest (p < 0.001), although at 3700 m the
      rS(O(2) ) was preserved better in those who took Actz (55.3 +/- 4.3% versus 47.9
      +/- 5.7%, p < 0.05). Irrespective of Actz use, with altitude, the percentage of
      omissions in the vigilance and tracking test increased while the climbers' scores
      on vigor decreased (p < 0.05). In conclusion, at altitude, exercise-induced
      reduction in cerebral oxygenation is less in climbers on Actz compared to
      climbers not taking Actz. This effect is nullified after several weeks at
      altitude due to acclimatization in climbers not taking Actz.

PMID- 17173515
TI  - Sustained acclimatization in Chilean mine workers subjected to chronic
      intermittent hypoxia.
AB  - Farias, Jorge G., Jorge Osorio, Gustavo Soto, Julio Brito, Patricia Siques, and
      Juan G. Reyes. Sustained acclimatization in Chilean mine workers subjected to
      chronic intermittent hypoxia. High Alt. Med. Biol. 7:302-306, 2006--We wanted to
      know if sea-level mine workers exposed previously to chronic intermittent hypoxia
      reached a steady acclimatization at 36 months under hypobaric hypoxia. An
      intermittently exposed group of mine workers (IE, n = 25) were subjected to
      submaximal exercise (100 W) at 4500 m. Their systolic blood pressure (SBP),
      diastolic blood pressure (DBP), heart rate (HR), and hemoglobin oxygen saturation
      (HbSatO(2)) were monitored. Two comparison groups of unacclimatized sea-level
      workers (n = 17) were studied. A nonexposed group (NE) performed 5 min of
      submaximal exercise at sea level. Some kind of exercise was performed both by an
      acutely exposed group (AE) and IE group at 4500 m. No statistical differences
      were found for HR, SBP, and DBP (p > 0.05) during exercise between IE and AE
      groups. Resting HbSatO(2) of IE (87 +/- 6%) was lower than NE (97 +/- 3%) (p <
      0.05), but was higher than AE (82 +/- 4%) (p < 0.05). In the exercise condition,
      HbSatO(2) of IE (85 +/- 5%) was lower than NE (95 +/- 3%) (p < 0.05), but was
      higher than AE (76 +/- 2%) (p < 0.05). These responses were maintained through
      the 6 months of the study period. Thus, mine workers subjected to intermittent
      hypobaric condition for 3 years showed a good degree of acclimatization that was
      maintained through time.

PMID- 17173516
TI  - Supplemental oxygen and sleep at altitude.
AB  - Windsor, Jeremy S., and George W. Rodway. Supplemental oxygen and sleep at
      altitude. High Alt. Med. Biol. 7:307-311, 2006.--The purpose of this study was to
      examine the effect supplemental oxygen has on the respiratory and cardiovascular
      system of a mountaineer during sleep at high altitude by using a novel
      ambulatory, multisensor, continuous monitoring device. Supplemental oxygen was
      administered to a healthy subject via a nasal demand system (0, 16.7, 33.3, or 50
      mL/sec per pulse dose delivered over 1 sec) during the first three nights of
      sleep at 4900 and 5700 m. Increases in pulse dose resulted in a consistent rise
      in Sa(O(2)) and a fall in minute ventilation (p < 0.05). The 50-mL pulse dose
      resulted in the greatest changes, with an increase in Sa(O(2)) from 68.5% to 81%
      (p < 0.05) and a fall in minute ventilation from 13.1 to 10.9 L/min (p < 0.05)
      being noted. Changes in Sa(O(2)) and minute ventilation also coincided with a
      fall in apnea/hypopnea index (AHI). At 4900 m the AHI fell from 12.5-52.3
      (breathing air) to 0-7.5 (50-mL oxygen pulse), whereas at 5700 m a decrease from
      49.1-80.4 to 3.5-10.0 was observed. No changes in respiratory rate or heart rate
      were identified when different pulse doses were compared (p < 0.05). The
      multisensor monitoring device proved to be a highly effective system,
      demonstrating marked improvements in Sa(O(2)), tidal volume, and AHI in our
      participant when supplemental oxygen was administered via a nasal demand system.

PMID- 17173518
TI  - High altitude medicine and biology advanced research workshop, Issyk-Kul,
      Kyrgyzstan, June 5-8, 2006.

PMID- 17173517
TI  - Symptoms of acute mountain sickness in Sherpas exposed to extremely high
      altitude.
AB  - Droma, Yunden, Masayuki Hanaoka, Buddha Basnyat, Amit Arjyal, Pritam Neupane,
      Anil Pandit, Dependra Sharma, and Keishi Kubo. Symptoms of acute mountain
      sickness in Sherpas exposed to extremely high altitude. High Alt. Med. Biol.
      7:312-314, 2006.--The aim of this field interview was to investigate the current
      state of affairs concerning acute mountain sickness (AMS) in high-altitude
      residents, specifically the Sherpas at 3440 m above sea level, when they are
      exposed rapidly to altitudes significantly higher than their residing altitudes.
      Out of 105 Sherpas (44 men and 61 women, 31.2 +/- 0.8 yr), 104 had mountain
      climbing experiences to 5701.4 +/- 119.1-m altitude in average 3.5 times each
      year. On the other hand, only 68 out of 111 non-Sherpas (29.9 +/- 0.8 yr) had
      experience of 1.4 +/- 1.5 climbs to an average 2688.6 +/- 150.4-m altitude in
      their mountaineering histories (p < 0.0001). Among the 104 Sherpas, 45 (43.3%)
      complained of at least one AMS symptom (headache, gastrointestinal symptoms,
      weakness, dizziness, and difficulty sleeping) in their experiences of
      mountaineering at an average 5518.9 +/- 195.9-m altitude. And 16 out of the 68
      non-Sherpas (23.5%) reported the AMS symptoms at a mean altitude of 2750.0 +/-
      288.8 m. Moreover, we also noticed that the Sherpa women showed a significantly
      higher Sa(O(2) ) (93.9 +/- 0.2%) than did Sherpa men (92.4 +/- 0.3%, p = 0.0001)
      at an altitude of 3440 m. The brief field interview evidenced that Sherpas might
      suffer from AMS when exposed to altitudes significantly higher than their
      residing altitude.

PMID- 17173522
TI  - Readers offer insight on food animal veterinarian shortage.

PMID- 17173523
TI  - What is your diagnosis? Avulsion of the popliteal tendon.

PMID- 17173524
TI  - What is your diagnosis? Renal disease resulting in aortic metastatic
      mineralization.

PMID- 17173525
TI  - ECG of the Month. Atrial fibrillation secondary to hypoadrenocorticism.

PMID- 17173526
TI  - Anesthesia case of the month.

PMID- 17173527
TI  - Rabies surveillance in the United States during 2005.
AB  - During 2005, 49 states and Puerto Rico reported 6,417 cases of rabies in nonhuman
      animals and 1 case in a human being to the CDC, representing a 6.2% decrease from
      the 6,836 cases in nonhuman animals and 8 cases in human beings reported in 2004.
      Approximately 92% of the cases were in wildlife, and 8% were in domestic animals.
      Relative contributions by the major animal groups were as follows: 2,534 raccoons
      (39.5%), 1,478 skunks (23%), 1,408 bats (21.9%), 376 foxes (5.9%), 269 cats
      (4.2%), 93 cattle (1.5%), and 76 dogs (1.2%). Compared with numbers of reported
      cases in 2004, cases in 2005 decreased among all groups, except bats, horses, and
      other wild animals. Decreases in numbers of rabid raccoons during 2005 were
      reported by 10 of the 20 eastern states in which raccoon rabies was enzootic and
      decreased overall by 1.2%, compared with 2004. On a national level, the number of
      rabies cases in skunks during 2005 decreased 20.4% from the number reported in
      2004. Once again, Texas reported the greatest number (n = 392) of rabid skunks
      and the greatest overall state total of rabies cases (741). Texas reported no
      cases of rabies associated with the dog/coyote rabies virus variant and only 8
      cases associated with the Texas gray fox rabies virus variant (compared with 22
      cases in 2004). The total number of cases of rabies reported nationally in foxes
      decreased 3.3%, compared with those reported in 2004. The 1,408 cases of rabies
      reported in bats represented a 3.5% increase over numbers reported in 2005. Cases
      of rabies in cats, dogs, cattle, and sheep and goats decreased 4.3%, 19.2%,
      19.1%, and 10%, respectively, whereas cases reported in horses and mules
      increased 9.3%. In Puerto Rico, reported cases of rabies in mongooses increased
      29.8%, and rabies in domestic animals decreased 37.5%. One case of human rabies
      was reported from Mississippi during 2005. This case was submitted by the state
      to the CDC's unexplained deaths project and diagnosed as rabies retrospectively.

PMID- 17173528
TI  - Consensus recommendations on diagnostic testing for the detection of
      paratuberculosis in cattle in the United States.
AB  - The report provided here contains a simplified set of diagnostic testing
      recommendations. These recommendations were developed on the basis of research
      funded by the USDA-Animal and Plant Health Inspection Service-Veterinary Services
      through a cooperative agreement. The report is intended to provide simple,
      practical, cost-effective consensus testing recommendations for cattle herds that
      are not enrolled in the US Test-Negative Program. The information has been
      reviewed by paratuberculosis (Johne's disease) experts at the USDA and academic
      centers as well as stakeholders in various segments of the cattle industry. The
      recommendations were accepted by the National Johne's Working Group and Johne's
      Disease Committee of the US Animal Health Association during their annual
      meetings in October 2006. The report is intended to aid veterinarians who work
      with cattle producers in the United States. The recommendations are based on
      information available up to October 2006. There is a paucity of large-scale, high
      quality studies of multiple tests conducted on samples obtained from the same
      cattle. It is understood that there may be special circumstances that require
      deviation from these recommendations. Furthermore, as new information becomes
      available and assays are improved and their accuracy is critically evaluated,
      changes to these recommendations may be necessary.

PMID- 17173530
TI  - Agreement between computed tomography, magnetic resonance imaging, and surgical
      findings in dogs with degenerative lumbosacral stenosis.
AB  - OBJECTIVE: To assess the extent of agreement between computed tomography (CT),
      magnetic resonance imaging (MRI), and surgical findings in dogs with degenerative
      lumbosacral stenosis. DESIGN: Observational study. ANIMALS: 35 dogs with
      degenerative lumbosacral stenosis. PROCEDURES: Results of preoperative CT and MRI
      were compared with surgical findings with respect to degree and location of disk
      protrusion, position of the dural sac, amount of epidural fat, and swelling of
      spinal nerve roots. RESULTS: A lumbosacral step was seen on radiographic images
      from 22 of 32 (69%) dogs, on CT images from 23 of 35 (66%) dogs, and on MR images
      from 21 of 35 (60%) dogs. Most dogs had slight or moderate disk protrusion that
      was centrally located. There was substantial or near perfect agreement between CT
      and MRI findings in regard to degree of disk protrusion (kappa, 0.88), location
      of disk protrusion (0.63), position of the dural sac (0.89), amount of epidural
      fat (0.72), and swelling of spinal nerve roots (0.60). The degree of agreement
      between CT and surgical findings and between MRI and surgical findings was
      moderate in regard to degree and location of disk protrusion (kappa, 0.44 to
      0.56) and swelling of spinal nerve roots (0.40 and 0.50). CONCLUSIONS AND
      CLINICAL RELEVANCE: Results indicate that there is a high degree of agreement
      between CT and MRI findings in dogs with degenerative lumbosacral stenosis but
      that the degree of agreement between diagnostic imaging findings and surgical
      findings is lower.

PMID- 17173533
TI  - Risk factors associated with short-term outcome and development of perioperative
      complications in dogs undergoing surgery because of gastric dilatation-volvulus:
      166 cases (1992-2003).
AB  - OBJECTIVE: To evaluate risk factors associated with death and development of
      perioperative complications in dogs undergoing surgery for treatment of gastric
      dilatation-volvulus (GDV). DESIGN: Retrospective case series. ANIMALS: 166 dogs.
      PROCEDURES: Records of dogs with confirmed GDV that underwent surgery were
      reviewed. Logistic regression was performed to identify factors associated with
      development of complications (ie, hypotension, arrhythmias, gastric necrosis
      necessitating gastrectomy, disseminated intravascular coagulation, peritonitis,
      sepsis, postoperative dilatation, postoperative vomiting, and incisional
      problems) and with short-term outcome (ie, died vs survived to the time of suture
      removal). RESULTS: Short-term mortality rate was 16.2% (27/166). Risk factors
      significantly associated with death prior to suture removal were clinical signs
      for > 6 hours prior to examination, combined splenectomy and partial gastrectomy,
      hypotension at any time during hospitalization, peritonitis, sepsis, and
      disseminated intravascular coagulation. Partial gastrectomy was not a significant
      risk factor for death but was for peritonitis, disseminated intravascular
      coagulation, sepsis, and arrhythmias. Age, gastrectomy, and disseminated
      intravascular coagulation were risk factors for development of hypotension. Use
      of a synthetic colloid or hypertonic saline solution was associated with a
      significantly decreased risk of hypotension. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that the prognosis for dogs undergoing surgery because of GDV is
      good but that certain factors are associated with an increased risk that dogs
      will develop perioperative complications or die.

PMID- 17173531
TI  - Idiopathic primary chylopericardium in a dog.
AB  - CASE DESCRIPTION: A 7-year-old spayed female Labrador Retriever was evaluated
      because of pericardial effusion. CLINICAL FINDINGS: The dog had a history of
      decreased appetite and exercise intolerance of 3 days' duration. Thoracic
      radiography performed by the referring veterinarian revealed a large cardiac
      silhouette. Heart sounds were muffled. Echocardiographic findings were indicative
      of severe pericardial effusion with cardiac tamponade; no pleural effusion was
      identified. Pericardiocentesis yielded a considerable amount of chylous fluid. A
      diagnosis of chylopericardium in the absence of pleural effusion was made.
      TREATMENT AND OUTCOME: Conservative management was not effective, and subtotal
      pericardectomy and thoracic duct ligation were recommended. Surgery was postponed
      by the owners for 25 days, at which time the dog had both chylopericardium and
      chylothorax. The dog underwent subtotal pericardectomy and thoracic duct
      ligation; to delineate the thoracic duct, intraoperative lymphangiography was
      performed by injection of a radiopaque contrast agent directly into a mesenteric
      lymph node and subsequent injection of methylene blue solution into another
      mesenteric lymph node. Surgical treatment resulted in complete resolution of the
      clinical signs and pleural effusion. CLINICAL RELEVANCE: To the authors'
      knowledge, this is the first report of the development of chylopericardium prior
      to development of chylothorax in a dog. Treatment with thoracic duct ligation and
      pericardectomy resulted in complete resolution of the effusion and clinical
      signs.

PMID- 17173534
TI  - Influence of exercise on thermographically determined surface temperatures of
      thoracic and pelvic limbs in horses.
AB  - OBJECTIVE: To determine the amount of time required for surface temperatures of
      thoracic and pelvic limbs in horses to return to pre-exercise temperatures after
      high-speed treadmill exercise, as detected via infrared thermographic imaging.
      DESIGN: Prospective study. ANIMALS: 6 Thoroughbreds. PROCEDURES: All horses had
      been trained on and conditioned to use of a high-speed treadmill. Baseline
      thermographic images were obtained 3 days prior to exercise (baseline). Horses
      were exercised on a treadmill at a walk for 5 minutes, a slow trot (3 m/s) for 5
      minutes, a trot (5 to 6 m/s) for 5 minutes, and a slow gallop (6 to 8 m/s) for 5
      minutes, then back to a trot for 3 minutes, a slow trot for 3 minutes, and a walk
      for 3 minutes prior to stopping. Thermal images were obtained immediately after
      stopping exercise (0 minutes) and 5, 15, 45, and 60 minutes and 6 hours after
      stopping exercise. Ambient temperature surrounding each horse was recorded.
      RESULTS: In all regions, significant differences in surface temperatures were
      detected between thermograms obtained before exercise and those obtained
      immediately after, 5 minutes after, and 15 minutes after exercise was stopped.
      There were no significant differences in surface temperatures between thermograms
      obtained before exercise and those obtained > or = 45 minutes after exercise was
      stopped. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, images generated via
      infrared thermography are not influenced by exercise-generated heat > or = 45
      minutes after exercise is stopped.

PMID- 17173535
TI  - Progression of mycosis of the auditory tube diverticulum (guttural pouch) after
      arterial occlusion in a horse with contralateral temporohyoid osteoarthropathy.
AB  - CASE DESCRIPTION: A 6-year-old Appaloosa mare was examined because of
      inappetance, difficulty eating, and swelling and mucopurulent discharge in the
      right eye. CLINICAL FINDINGS: Results of a CBC and serum bio-chemical analysis
      revealed no important findings. Ophthalmologic examination revealed scarring and
      ulceration of the superficial layers of the cornea. Endoscopic examination of the
      upper portion of the respiratory tract and auditory tube diverticula (guttural
      pouches) revealed abnormal thickness of the right stylohyoid bone and a plaque
      suggestive of mycotic growth on the left internal carotid artery. Radiographic
      examination revealed right-sided otitis media. Temporohyoid osteoarthropathy in
      the right guttural pouch and mycosis in the left guttural pouch were diagnosed.
      TREATMENT AND OUTCOME: Ceratohyoidectomy of the right stylohyoid bone was
      performed, and the left internal carotid artery was occluded via placement of
      stainless steel spring embolization coils. The mare regained the ability to eat
      without difficulty and improved clinically for approximately 4 weeks. However,
      the mare returned to the medical center 53 days after surgery with left-sided
      Horner syndrome, atrophy of the right side of the tongue, and a 3-week history of
      dysphagia and weight loss. Endoscopic evaluation revealed progression of mycotic
      growth in the left guttural pouch. The mare was euthanatized. CLINICAL RELEVANCE:
      Although the mycotic lesion in the left guttural pouch was an incidental finding
      at the time of initial examination, the lesion progressed to cause dysphagia and
      Horner syndrome after occlusion of the left internal carotid artery, a treatment
      that is typically associated with resolution of guttural pouch mycosis. Arterial
      occlusion is not necessarily a reliable method of resolving guttural pouch
      mycosis.

PMID- 17173536
TI  - Evaluation of the rate of development of septic arthritis after elective
      arthroscopy in horses: 7 cases (1994-2003).
AB  - OBJECTIVE: To determine the rate of development of septic arthritis after
      elective arthroscopy and evaluate associations between various factors and
      development of this complication in horses. DESIGN: Retrospective case series.
      ANIMALS: 682 horses that underwent arthroscopic procedures at the University of
      Illinois Veterinary Teaching Hospital from 1994 to 2003. PROCEDURES: Information
      pertaining to signalment, joints treated, whether antimicrobials were
      administered, and development of postoperative septic arthritis was collected
      from medical records. Horses with a primary problem of septic arthritis or wounds
      involving joints were excluded. The following factors were evaluated to determine
      their roles in joint sepsis: breed, sex, joint, and preoperative and intra
      articular administration of antimicrobials. Telephone interviews with clients
      were used to determine whether unreported septic arthritis had developed.
      RESULTS: 8 of 932 (0.9%) joints in 7 of 682 (1.0%) horses that underwent
      arthroscopy developed postoperative septic arthritis. Follow-up information after
      discharge from the hospital was available for 461 of the 682 horses, and of
      those, 8 of 627 (1.3%) joints in 7 of 461 (1.5%) horses developed septic
      arthritis. Breed and joint treated were significant risk factors for development
      of postoperative septic arthritis, with draft breeds and tibiotarsal joints more
      likely than others to be affected. Sex, preoperatively administered
      antimicrobials, and intra-articularly administered antimicrobials were not
      associated with development of postoperative septic arthritis. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results can be used for comparison with data from other
      institutions and surgical facilities. Additional precautions should be undertaken
      when arthroscopic surgery involves draft breeds and tibiotarsal joints.

PMID- 17173538
TI  - Effects of duration of capture and sample handling on critical care blood
      analytes in free-ranging bottlenose dolphins.
AB  - OBJECTIVE: To determine effects of duration of capture and sample-handling
      procedures on blood analytes in free-ranging bottlenose dolphins. DESIGN: Cross
      sectional study. ANIMALS: 154 free-ranging bottlenose dolphins of various ages
      and both sexes. PROCEDURES: Blood samples were drawn from each dolphin within 10
      minutes of capture and before release and analyzed by use of a portable analyzer
      with a single-use 8-analyte disposable cartridge. Analyte values were compared
      according to duration between sample acquisition and analysis (time to run [TTR])
      and duration between net encirclement and sample acquisition (time to bleed
      [TTB]). RESULTS: Neither TTB nor TTR significantly affected sodium or chloride
      concentration. Potassium concentration was not significantly affected by TTR,
      whereas the effect of TTB was significant. Glucose, total CO(2), HCO(3), Hct, and
      base excess of extracellular fluid values were significantly affected by TTR.
      Increased TTB resulted in significantly increased total CO(2), HCO(3), and base
      excess when TTR was kept within 10 minutes. CONCLUSIONS AND CLINICAL RELEVANCE:
      The effect of TTB on certain acid-base and electrolyte values was readily
      measured in free-ranging bottlenose dolphins, and such values may provide a
      reference range for those variables.

PMID- 17173539
TI  - Health impact assessment: a tool to help policy makers understand health beyond
      health care.
AB  - Health impact assessment (HIA)--a combination of methods to examine formally the
      potential health effects of a proposed policy, program, or project--has received
      considerable interest over the past decade internationally as a practical
      mechanism for collaborating with other sectors to address the environmental
      determinants of health and to achieve more effectively the goals of population
      health promotion. Demand for HIA in the United States seems to be growing. This
      review outlines the common principles and methodologies of HIA and compares
      different approaches to HIA. Lessons learned from the related field of
      environmental impact assessment and from experience with HIA in other countries
      are examined. Possible avenues for advancing both the field and the broader goals
      of population health promotion are outlined.

PMID- 17173540
TI  - Unusual phyletic distribution of peptidases as a tool for identifying potential
      drug targets.
AB  - Eukaryote homologues of carboxypeptidases Taq have been discovered by Niemirowicz
      et al. in the protozoan Trypanosoma cruzi, the causative agent of Chagas'
      disease. This is surprising, because the peptidase family was thought to be
      restricted to bacteria and archaea. In this issue of the Biochemical Journal, the
      authors propose that the Trypanosoma carboxypeptidases are potential drug targets
      for treatment of the disease. The authors also propose that the presence of the
      genes in the zooflagellates can be explained by a horizontal transfer of an
      ancestral gene from a prokaryote. Because peptidases are popular drug targets,
      identifying parasite or pathogen peptidases that have no homologues in their
      hosts would be a method to select the most promising targets. To understand how
      unusual this phyletic distribution is among the 183 families of peptidases,
      several other examples of horizontal transfers are presented, as well as some
      unusual losses of peptidase genes.

PMID- 17173543
TI  - Effect of oral glucose loading on endothelial function in normal-weight and
      overweight children.
AB  - The aim of the present study was to investigate the impact of acute
      hyperglycaemia on endothelial function in both normal-weight and overweight
      children. A total of 16 overweight [BMI (body mass index) > or =85th percentile]
      and 15 normal-weight (BMI <85th percentile) children were evaluated for FMD (flow
      mediated dilation) at baseline and 30, 60 and 120 min after glucose ingestion. At
      15 min following the measurement of the final FMD, 0.3 mg of sublingual
      nitroglycerine was administered and the brachial artery was imaged in order to
      assess endothelium-independent dilation. By design, the overweight children were
      significantly heavier (63.2+/-4.6 compared with 41.3+/-2.5 kg; P=0.0003) and had
      a greater percentage body fat (43.9+/-1.8 compared with 23.8+/-2.05%; P<0.0001)
      than the normal-weight children. The area under the curve in response to glucose
      administration was significantly (P<0.0001) greater in the overweight group for
      both glucose and insulin. The FMD area under the curve was not significantly
      different at baseline or between time points after glucose ingestion, nor was
      there a difference in response between the two groups. Endothelium-independent
      dilation in the normal-weight group was significantly greater compared with the
      overweight group (26.7+/-1.6 compared with 20.2+/-2.0% respectively; P=0.019). In
      conclusion, these results suggest that acute elevation of glucose and insulin in
      overweight and normal-weight children are not associated with impairment in
      endothelial function.

PMID- 17173541
TI  - Metabolite transport across the peroxisomal membrane.
AB  - In recent years, much progress has been made with respect to the unravelling of
      the functions of peroxisomes in metabolism, and it is now well established that
      peroxisomes are indispensable organelles, especially in higher eukaryotes.
      Peroxisomes catalyse a number of essential metabolic functions including fatty
      acid beta-oxidation, ether phospholipid biosynthesis, fatty acid alpha-oxidation
      and glyoxylate detoxification. The involvement of peroxisomes in these metabolic
      pathways necessitates the transport of metabolites in and out of peroxisomes.
      Recently, considerable progress has been made in the characterization of
      metabolite transport across the peroxisomal membrane. Peroxisomes posses several
      specialized transport systems to transport metabolites. This is exemplified by
      the identification of a specific transporter for adenine nucleotides and several
      half-ABC (ATP-binding cassette) transporters which may be present as hetero- and
      homo-dimers. The nature of the substrates handled by the different ABC
      transporters is less clear. In this review we will describe the current state of
      knowledge of the permeability properties of the peroxisomal membrane.

PMID- 17173544
TI  - The symbiotic ion channel homolog DMI1 is localized in the nuclear membrane of
      Medicago truncatula roots.
AB  - Legumes utilize a common signaling pathway to form symbiotic associations both
      with rhizobial bacteria and arbuscular mycorrhizal fungi. The perception of
      microbial signals is believed to take place at the plasma membrane, activating a
      cascade that converges on the nucleus where transcriptional reprogramming
      facilitates the symbioses. Forward genetic strategies have identified genes in
      this signaling pathway including Medicago truncatula DMI1 (Doesn't Make
      Infections 1) that encodes a putative ion channel. Although the DMI1 homologs
      from Lotus japonicus, CASTOR and POLLUX, were recently reported to be localized
      in plastids, we report here that a functional DMI1::GFP fusion is localized to
      the nuclear envelope in M. truncatula roots when expressed both from a
      constitutive 35S promoter and from a native DMI1 promoter. Localization may be
      mediated in part by sequences located within the amino-terminus of DMI1. This
      region of DMI1 is required for symbiotic signal transduction, and its replacement
      with a bona fide plastid transit peptide from the glutamine synthetase 2 gene
      does not restore DMI1 function. These new data place DMI1 in the nuclear envelope
      in close proximity to the origin of Nod-factor-induced calcium spiking.

PMID- 17173542
TI  - Big roles for small GTPases in the control of directed cell movement.
AB  - Small GTPases are involved in the control of diverse cellular behaviours,
      including cellular growth, differentiation and motility. In addition, recent
      studies have revealed new roles for small GTPases in the regulation of eukaryotic
      chemotaxis. Efficient chemotaxis results from co-ordinated chemoattractant
      gradient sensing, cell polarization and cellular motility, and accumulating data
      suggest that small GTPase signalling plays a central role in each of these
      processes as well as in signal relay. The present review summarizes these recent
      findings, which shed light on the molecular mechanisms by which small GTPases
      control directed cell migration.

PMID- 17173545
TI  - Telomerase activity coevolves with body mass not lifespan.
AB  - In multicellular organisms, telomerase is required to maintain telomere length in
      the germline but is dispensable in the soma. Mice, for example, express
      telomerase in somatic and germline tissues, while humans express telomerase
      almost exclusively in the germline. As a result, when telomeres of human somatic
      cells reach a critical length the cells enter irreversible growth arrest called
      replicative senescence. Replicative senescence is believed to be an anticancer
      mechanism that limits cell proliferation. The difference between mice and humans
      led to the hypothesis that repression of telomerase in somatic cells has evolved
      as a tumor-suppressor adaptation in large, long-lived organisms. We tested
      whether regulation of telomerase activity coevolves with lifespan and body mass
      using comparative analysis of 15 rodent species with highly diverse lifespans and
      body masses. Here we show that telomerase activity does not coevolve with
      lifespan but instead coevolves with body mass: larger rodents repress telomerase
      activity in somatic cells. These results suggest that large body mass presents a
      greater risk of cancer than long lifespan, and large animals evolve repression of
      telomerase activity to mitigate that risk.

PMID- 17173546
TI  - BIRB 796 enhances cytotoxicity triggered by bortezomib, heat shock protein (Hsp)
      90 inhibitor, and dexamethasone via inhibition of p38 mitogen-activated protein
      kinase/Hsp27 pathway in multiple myeloma cell lines and inhibits paracrine tumour
      growth.
AB  - We have previously shown that heat shock protein (Hsp) 27 or its upstream
      activator p38 mitogen-activated protein kinase (MAPK) confers resistance to
      bortezomib and dexamethasone (Dex) in multiple myeloma (MM) cells. This study
      examined anti-MM activity of a novel p38 MAPK inhibitor, BIRB 796, alone and in
      combination with conventional and novel therapeutic agents. BIRB 796 blocked
      baseline and bortezomib-triggered upregulation of p38 MAPK and Hsp27
      phosphorylation, thereby enhancing cytotoxicity and caspase activation. The Hsp90
      inhibitor 17-allylamino-17-demethoxy-geldanamycin (17-AAG) upregulated protein
      expression and phosphorylation of Hsp27; conversely, BIRB 796 inhibited this
      phosphorylation and enhanced 17-AAG-induced cytotoxicity. Importantly, BIRB 796
      inhibited Hsp27 phosphorylation induced by 17-AAG plus bortezomib, thereby
      enhancing cytotoxicity. In bone marrow stromal cells (BMSC), BIRB 796 inhibited
      phosphorylation of p38 MAPK and secretion of interleukin-6 (IL-6) and vascular
      endothelial growth factor triggered by either tumour necrosis factor-alpha or
      tumour growth factor-beta1. BIRB 796 also inhibited IL-6 secretion induced in
      BMSCs by adherence to MM cells, thereby inhibiting tumour cell proliferation.
      These studies therefore suggest that BIRB 796 overcomes drug-resistance in the BM
      microenvironment, providing the framework for clinical trials of a p38 MAPK
      inhibitor, alone and in combination with bortezomib, Hsp90 inhibitor, or Dex, to
      improve patient outcome in MM.

PMID- 17173550
TI  - In vitro reconstituted skin as a tool for biology, pharmacology and therapy: a
      review.
AB  - Various culture procedures, suitable to maintain the differentiated phenotype of
      various types of cells in vitro, have been devised during the past decade. These
      culture systems use macromolecular components extracted from extracellular
      matrixes or synthetic polymers which provide cells with a three-dimensional,
      spatially structured support. Substantial information has come from the use of
      collagen lattices. Many types of cells, of mesenchymal or other origin, are able
      to organize collagen fibrils in these models and to form a connective tissue-like
      structure. Prerequisites for this process are active function of the cytoskeleton
      and the expression of alpha(2)beta(1) integrin collagen receptors. Interaction of
      cells with such a matrix has profound effects on morphologic status,
      proliferation, cellular metabolism, and state of differentiation. The in vitro
      procedures reviewed and described in this article offer the possibility to
      combine different types of cells to approximate the in vivo environment and to
      investigate such physiologic processes as cell-cell and cell-matrix interactions
      which are otherwise not easily accessible. In pathologic conditions of the skin,
      these models have proven to be useful tools in investigating diseases relating to
      impaired recognition of extracellular matrix structures or alterations of
      cytoskeletal assembly. In pharmacologic and toxicologic studies, activity of
      drugs and potentially useful therapeutic substances has been evaluated. The use
      of cells and matrix components derived from skin has lead to refined systems
      which could be adapted and extended to other organs in an attempt to better
      understand pathophysiologic mechanisms.

PMID- 17173548
TI  - Identification and characterization of a nuclear receptor subfamily I member in
      the Platyhelminth Schistosoma mansoni (SmNR1).
AB  - A cDNA encoding a nuclear receptor subfamily I member in the platyhelminth
      Schistosoma mansoni (SmNR1) was identified and characterized. SmNR1 cDNA is 2406
      bp long and contains an open reading frame encoding a 715 residue protein.
      Phylogenetic analysis demonstrates that SmNR1 is a divergent member of nuclear
      receptor subfamily I with no known orthologue. SmNR1 was localized to S. mansoni
      chromosome 1 by fluorescent in situ hybridization. Gene structure of SmNR1 was
      determined showing it to consist of eight exons spanning more than 14 kb.
      Quantitative real-time RT-PCR showed that SmNR1 was expressed throughout
      schistosome development with a higher expression in eggs, sporocysts and 21-day
      worms. SmNR1 contains an autonomous transactivation function (AF1) in the A/B
      domain as demonstrated in a yeast one-hybrid assay; it interacts with SmRXR1 in a
      yeast two-hybrid assay and in a glutathione S-transferase pull-down assay.
      Electrophoretic mobility shift assay showed that SmNR1 could form a heterodimer
      with SmRXR1 to bind to DNA elements containing the half-site AGGTCA, a direct
      repeat of the half-site separated by 0-5 nucleotides (DR1-DR5) and a palindrome
      repeat of the half-site not separated by nucleic acids (Pal0). Transient
      transfection in mammalian COS-7 cells showed that SmNR1/SmRXR1 could enhance the
      transcriptional activation of a DR2-dependent reporter gene. Our results
      demonstrate that SmNR1 is a partner of SmRXR1.

PMID- 17173551
TI  - Exchange and the mechanical properties of the skin: oncotic and hydrostatic
      forces control by blood supply and lymphatic drainage.
AB  - Unwounded healthy skin can survive several hours without oxygen. The rich blood
      supply of the skin is important for thermoregulation, mostly only above the
      waist. Why then, does the skin of even the big toe have a rich blood supply? That
      exchange requirements are more for fluid in support of turgor and that this
      process is essential for the mechanical properties of the skin is suggested. It
      is argued that the supposed richness of blood supply is not sufficient for wound
      healing, and thus a new organ, granulation tissue, has to be grown. However,
      granulation tissue is mechanically inappropriate for the protective mechanical
      function of the skin and must be completely removed before healing is complete.

PMID- 17173552
TI  - Localization of platelet-derived growth factor receptor subunit expression in
      chronic venous leg ulcers.
AB  - Cellular responses to platelet-derived growth factor, which affects all phases of
      the wound healing process, are dependent on the interaction of the growth factor
      with its cell surface receptors. Recently, we have shown that the platelet
      derived growth factor-receptor was not expressed in uninjured human skin. In
      acute human wounds healing by secondary intention, both platelet-derived growth
      factor-receptor subunits were coordinately expressed, whereas no expression was
      found after reepithelialization at day 47. Even though impaired wound healing may
      be due to uncoordinated expression or the failure to express platelet-derived
      growth factor-receptor subunits, little is known regarding their expression in
      chronic ulcers. We studied the localization of platelet-derived growth factor
      receptor expression in chronic venous leg ulcers of 15 patients with a median age
      of 73 years. Cryostat sections of biopsy specimens were immunostained with the
      use of antibodies against the alpha- and the beta-platelet-derived growth factor
      subunits. RNA was extracted from biopsy specimens and subjected to Northern blot
      analysis with the use of oligolabeled complementary DNA for the platelet-derived
      growth factor-receptor. Platelet-derived growth factor-receptor alpha- and beta
      subunit expression was found in fibroblast-like cells within the wound bed and in
      cells beneath the epidermis of the wound edge. Platelet-derived growth factor
      receptor beta-subunit expression was detected in endothelial cells of the
      vessels, in the granulation tissue, and the wound edge, whereas platelet-derived
      growth factor-receptor alpha-subunit was not expressed in endothelial cells of
      the uninjured skin. This finding suggests that the platelet-derived growth factor
      alpha-subunit may be involved in vessel formation during tissue repair. Both
      platelet-derived growth factor-receptor subunits were expressed at the messenger
      RNA level indicating that the synthesis is at least partly regulated at a
      pretranslational level. As the cellular responsiveness to growth factors depends
      on their specific receptors, our finding that both platelet-derived growth factor
      receptor subunits are expressed in chronic venous ulcers substantiates the
      concept of therapeutic trials with recombinant platelet-derived growth factor.

PMID- 17173553
TI  - Involvement of proteolytic enzymes--plasminogen activators and matrix
      metalloproteinases--in the pathophysiology of pressure ulcers.
AB  - The role of matrix-degrading enzymes, particularly plasminogen activators and
      matrix metalloproteinases, in the acute wound healing response has been the focus
      of many scientific studies. Only recently have these classes of endogenously
      produced proteinases been studied with regard to their involvement in the chronic
      wound environment. Using both in situ histologic zymography and
      immunohistochemical techniques, we examined the distribution of plasminogen
      activators and matrix metalloproteinase in the granulation tissue of pressure
      ulcers. Using in situ histologic zymography, urokinase was found to be the
      predominant plasminogen activator activity in the chronic wound granulation
      tissue, with little or no tissue-type plasminogen activator activity. These
      results were confirmed with the use of immunohistochemical techniques. In
      contrast, tissue-type plasminogen activator was found to be constitutively
      expressed in normal skin. Levels of matrix metalloproteinases were also found to
      be elevated in the granulation tissue of pressure ulcers. Immunohistochemical
      localization of leukocyte-associated proteinases (PMN elastase and cathepsin G)
      suggested a highly inflamed environment within the pressure ulcer granulation
      tissue. These results suggest a highly proteolytic environment within the chronic
      wound.

PMID- 17173554
TI  - Examination of expanded polytetrafluoroethylene wound healing models.
AB  - The object of this animal study was to examine and further develop the expanded
      polytetrafluoroethylene wound healing model. The goal was to increase its
      potential for assessing wound healing by increasing yield, reducing variability,
      establishing the elements of a standard technique, and further testing its
      ability to detect variations of healing which have clinical significance.
      Expanded polytetrafluoroethylene implants of various dimensions and fabrications
      and several implantation and sterilization techniques were compared in rats.
      Hydroxyproline, DNA, and protein deposition into the expanded
      polytetrafluoroethylene implants as parameters for wound healing were assessed.
      Additionally, a 4 cm skin incision for tensile strength assessment was created.
      Wound healing was assessed under normal and corticosteroid-impaired healing
      conditions. The highest yield of collagen was found in the stiffer fabrication of
      expanded polytetrafluoroethylene with the larger pore size and after the more
      traumatic implantation technique of incisional placement. Variability was
      unaffected by fabrication, implantation technique, indexing by various geometric
      dimensions of the implant, sterilization, or sampling techniques. Variability was
      the same in the individual animals as in groups of animals. The expanded
      polytetrafluoroethylene method also detects the influence of antiinflammatory
      corticosteroids and reflects the tensile strength of incisional wounds made in
      other sites in the same animal.

PMID- 17173555
TI  - Comparison of the polyvinyl alcohol sponge and expanded polytetrafluoroethylene
      subcutaneous implants as models to evaluate wound healing potential in human
      beings.
AB  - Our current understanding of the complex processes involved in wound healing is
      based mainly on studies of animal models. Although this information has been
      useful, it may not totally reflect the response found in human beings. For
      example, human beings have a tendency to either "overheal," as seen in keloids
      and hypertrophic scar formation, or have deficient healing, as seen in chronic
      ulcer formation. No animal models are available to analyze these human clinical
      pathologic conditions. Therefore the objective of this study was to analyze the
      wound healing response in a large population (n = 40) of normal healthy human
      beings as a first step to begin studies of abnormal human wound healing.
      Simultaneously, a comparison was made between the polyvinyl alcohol implant and
      the expanded polytetrafluoroethylene implant model. Under sterile conditions with
      the use of local anesthesia, two preweighed polyvinyl alcohol implants and two
      standard 6 cm expanded polytetrafluoroethylene implants were placed
      subcutaneously in the upper arm of each subject. High-performance liquid
      chromatography was used to quantitate isoleucine and hydroxy-l-proline in acid
      hydrolysates of each implant. Isoleucine was used as an indicator of protein
      content in the tissue sample, whereas hydroxyproline reflected collagen content.
      No infectious or hemorrhagic complications were found in the 40 volunteers
      included in the study. No significant difference was found in isoleucine or
      hydroxy-l-proline content between postoperative day 7 polyvinyl alcohol implants
      and day 14 polyvinyl alcohol implants. In contrast, both isoleucine and hydroxy-l
      proline content were significantly increased in day 14 expanded
      polytetrafluoroethylene implants compared with day 7 implants (p < 0.005 and p <
      0.001, respectively). In addition, the ratio of hydroxy-l-proline to isoleucine
      was significantly increased in day 14 expanded polytetrafluoroethylene implants
      compared with day 7 expanded polytetrafluoroethylene and both day 7 and day 14
      polyvinyl alcohol implants (p < 0.001). This observation suggests that by 14 days
      implantation of expanded polytetrafluoroethylene stimulated an increased
      deposition of collagen. No significant differences were found in the hydroxy-l
      proline to isoleucine ratios among day 7 expanded polytetrafluoroethylene, day 7
      polyvinyl alcohol, and day 14 polyvinyl alcohol implants. Histologic analyses
      correlated with the biochemical findings. These results suggest that expanded
      polytetrafluoroethylene may be the preferred implant for studies designed to
      examine pathologic processes associated with retarded wound healing. In contrast,
      the polyvinyl alcohol implant may be better suited for studies where a low
      background response is required. Moreover, the extreme variability in normal
      healthy volunteers seen in this study correlates clinically with the finding
      that, among the normal adult human population, there is a heterogeneous wound
      healing response.

PMID- 17173556
TI  - Hyaluronan, heterogeneity, and healing: the effects of ultrapure hyaluronan of
      defined molecular size on the repair of full-thickness pig skin wounds.
AB  - The extracellular matrix macromolecule, hyaluronan, is thought to modulate wound
      healing. However, the molecular size of hyaluronan and contaminating associated
      proteins may be important determinants of these effects. We have examined the
      results of seven daily topical treatments of full-thickness skin wounds in pigs
      with ultrapure hyaluronan of defined molecular size. High molecular weight
      hyaluronan (>1000 kd) enhanced, whereas low molecular weight hyaluronan
      decreased, the rate of early wound contraction as compared with intermediate
      hyaluronan (molecular weight = 100 kd) and saline solution controls. Fracture
      strength at 21 days was reduced by high and intermediate molecular weight
      hyaluronan but not by low molecular weight hyaluronan. Wound perfusion, measured
      by means of a scanning laser-Doppler technique as a noninvasive indicator of
      angiogenesis, showed depression by high and intermediate molecular weight
      hyaluronan on day 3, but all forms of hyaluronan caused elevated blood flow on
      day 7. The architecture of granulation tissue in this wet healing model was
      highly organized, but no gross histologic differences were seen because of
      treatment. Different molecular species of hyaluronan have differential effects on
      contraction, angiogenesis, and the evolution of wound strength. Where hyaluronan
      is used as a treatment or vehicle for wounds, its precise composition should be
      specified.

PMID- 17173557
TI  - Effect of ultraviolet radiation-induced inflammation on epidermal wound healing.
AB  - To examine the influence of ultraviolet radiation, a potent inducer of
      interleukin-1 and other growth factors, on the rate of epidermal migration, we
      used a porcine model of wound healing. Wounds were treated in one of the
      following treatment groups: (1) two minimal erythema doses of ultraviolet
      radiation once daily for 2 days before wounding, (2) two minimal erythema doses
      of ultraviolet radiation once daily for 2 days before wounding followed with
      continuous treatment until all wounds were 100% epithelized, (3) or no
      ultraviolet radiation treatment until healing was complete. Using a macroscopic
      salt-split technique, we examined epidermal specimens macroscopically for
      epithelialization. Treatment both before and after ultraviolet radiation
      significantly enhanced epithelialization when compared with non-ultraviolet
      radiation-treated control wounds. These experiments show that ultraviolet
      radiation treatment can augment the rate of healing of partial-thickness wounds.

PMID- 17173558
TI  - Effects of insulin-like growth factor-I and insulin-like growth factor binding
      protein-1 on wound healing in a dermal ulcer model.
AB  - The effects on wound healing of insulin-like growth factor-I with and without
      insulin-like growth factor binding protein-1 were studied in a rabbit ear dermal
      ulcer model under both nonischemic and ischemic conditions. Wounds 6 mm in
      diameter were made on the ventral surface of rabbit ears for a total of 272
      wounds in the nonischemic group and 77 wounds in the ischemic group. Insulin-like
      growth factor-I in varying doses (1 to 43 microg) and in combination with varying
      molar ratios of the binding protein were added at time of wounding to each wound.
      Wounds were analyzed histomorphometrically on day 7 after wounding. We found that
      insulin-like growth factor-I or binding protein alone at varying doses did not
      have any effects on wound healing parameters. Low to moderate doses (1 microg and
      4 microg, respectively) of the combination of insulin-like growth factor-I with
      the binding protein in a molar ratio of 5:1 or 11:1 showed a 52% increase (p <
      0.05) in new granulation tissue in the nonischemic model compared with controls
      but did not significantly augment new granulation tissue formation in the
      ischemic wound model. A high dose (43 microg) at a 10:1 molar ratio of growth
      factor to binding protein was required to elicit significantly enhanced wound
      healing in ischemic wounds. These results indicate that insulin-like growth
      factor binding protein-1 modulates the effects of insulin-like growth factor-I in
      promoting wound healing in vivo and that the combination is a highly effective
      vulnerary compound with effects comparable in magnitude with other growth factors
      previously tested in this model.

PMID- 17173559
TI  - Mechanisms of TGF-beta action in connective tissue repair of rat mesenteric
      wounds.
AB  - We have recently reported that transforming growth factor-beta stimulates genuine
      connective tissue repair in the perforated rat mesentery and that this
      stimulation is not caused by increased macrophage chemotaxis. To further
      characterize the effect of transforming growth factor-beta(1) on the enhanced
      rate of wound closure, we performed a series of morphometric analyses with
      determination of mitotic index, fibroblast labeling index, cellular density,
      neovascularization, and scar tissue formation. Actin expression close to the
      wound margin was also evaluated morphologically. Fibroblast cell proliferation
      was not stimulated by transforming growth factor-beta(1) in either wounded or
      unwounded tissue. Transforming growth factor-beta(1) did, however, significantly
      increase the formation of healing tissue postoperative days 5 to 10 (p < 0.05)
      and angiogenesis was significantly stimulated by transforming growth factor
      beta(1) postoperative days 7 and 10 (p < 0.005). The mean cellular density was
      significantly increased in unperforated, transforming growth factor-beta(1)
      treated membranes from days 3 to 10, and increased expression of actin with time
      was observed close to the wound margin. Transforming growth factor-beta(1) was
      thus shown to be a potent stimulator of angiogenesis and healing tissue formation
      in connective tissue repair, but this stimulation mainly occurred after closure
      of perforations. The increased cellular density in the absence of stimulated
      proliferation and increased actin expression in wound cells indicate that
      contraction may be an important mechanism of connective tissue repair in the
      perforated rat mesentery.

PMID- 17173560
TI  - Acceleration of wound healing in aged rats by topical application of transforming
      growth factor-beta(1).
AB  - The impaired wound healing associated with aging may reflect inadequate secretion
      or delivery of cytokines. Transforming growth factor-beta(1) is a mitogenic
      polypeptide with beneficial effects on wound healing. In the present study we
      questioned whether topical administration of transforming growth factor-beta(1)
      could improve the wound healing process in aged rats in vivo. Wound repair (from
      1 to 14 days) was analyzed in full-thickness incisional wounds from 2-year-old
      rats with or without a single topical application of transforming growth factor
      beta(1) (1 microg/wound) at the time of wounding. Identical wounds from 3-month
      old, untreated rats served as controls. Histologic analysis showed a marked delay
      in several aspects of wound repair in the aged rats in comparison with that noted
      in the younger animals. Immunostaining of the wounds for proliferating cell
      nuclear antigen showed a reduction in the number of cycling fibroblasts in old
      rats. In addition, the number of capillaries per unit area of the wound as
      determined by a stain for Griffonin (Bandeiraea) simplicifolia lectin, and the
      number of inflammatory cells as identified by an antibody specific for
      macrophages, were also reduced in the wound area in old rats. Treatment with
      transforming growth factor-beta(1) resulted in marked enhancement of the
      following parameters: cell proliferation, inflammatory cell and fibroblast
      influx, wound closure, and angiogenesis. As seen with in situ hybridization, a
      similar temporal pattern of expression of messenger RNAs corresponding to type I
      procollagen and Secreted Protein, Acidic and Rich in Cysteine (osteonectin),
      known to be prevalent in healing wounds, was observed in both young and aged
      rats. However, the levels of mRNA corresponding to these secreted proteins
      appeared to be reduced in wound tissue from aged rats. Treatment with
      transforming growth factor-beta(1) subsequently resulted in an increase in the
      expression of both type I procollagen and Secreted Protein, Acidic and Rich in
      Cysteine mRNA in the wound tissue from aged rats. In summary, a single topical
      application of transforming growth factor-beta(1) to the wounds of aged rats at
      the time of wounding was associated with a healing response that, in all the
      parameters of wound repair examined, was similar to that of young rats. Topical
      transforming growth factor-beta(1) might therefore be beneficial in the treatment
      of dermal wounds in the aged.

PMID- 17173547
TI  - HIV-1 neuropathogenesis: glial mechanisms revealed through substance abuse.
AB  - Neuronal dysfunction and degeneration are ultimately responsible for the
      neurocognitive impairment and dementia manifest in neuroAIDS. Despite overt
      neuronal pathology, HIV-1 does not directly infect neurons; rather, neuronal
      dysfunction or death is largely an indirect consequence of disrupted glial
      function and the cellular and viral toxins released by infected glia. A role for
      glia in HIV-1 neuropathogenesis is revealed in experimental and clinical studies
      examining substance abuse-HIV-1 interactions. Current evidence suggests that glia
      are direct targets of substance abuse and that glia contribute markedly to the
      accelerated neurodegeneration seen with substance abuse in HIV-1 infected
      individuals. Moreover, maladaptive neuroplastic responses to chronic drug abuse
      might create a latent susceptibility to CNS disorders such as HIV-1. In this
      review, we consider astroglial and microglial interactions and dysfunction in the
      pathogenesis of HIV-1 infection and examine how drug actions in glia contribute
      to neuroAIDS.

PMID- 17173561
TI  - Combination of platelet-derived growth factor-BB and insulin-like growth factor-I
      is more effective than platelet-derived growth factor-BB alone in stimulating
      complete healing of full-thickness wounds in "older" diabetic mice.
AB  - Platelet-derived growth factor and insulin-like growth factor-I have been shown
      to interact synergistically to enhance repair of skin wounds in normal healing
      swine. Platelet-derived growth factor alone has shown promise in treating human
      chronic ulcers. The objective of this study was to compare the wound healing
      effects of platelet-derived growth factor-BB alone with those of a combination of
      platelet-derived growth factor-BB and insulin-like growth factor-I in an improved
      model with the use of "older" animals with diabetes. Older diabetic (db/db) mice
      (>15 weeks of age) have less elevated insulin levels compared with young db/db
      mice. The serum insulin levels in the older animals is 1.0 to 2.5 times that of
      the nondiabetic animals, a similar increase to that which occurs in human
      patients with type II diabetes. Healing was evaluated in two studies involving a
      total of 104 animals. Treatment groups included the following: 4.0 microg/cm(2)
      of platelet-derived growth factor-BB, 40.0 microg/cm(2) of platelet-derived
      growth factor-BB, 4.0 microg/cm(2) of both platelet-derived growth factor-BB and
      insulin-like growth factor-I or vehicle. All growth factors were applied
      topically in a methylcellulose vehicle to full-thickness wounds every other day
      for 24 days. Efficacy end points were median and mean time to complete healing
      and rate of wound closure. The median time to complete healing for animals
      receiving the platelet-derived growth factor-BB/insulin-like growth factor-I
      combination was 38% and 33% faster (p < 0.001) than animals receiving 4.0
      microg/cm(2) and 40.0 microg/cm(2) of platelet-derived growth factor-BB,
      respectively. The mean time to complete healing for platelet-derived growth
      factor/insulin-like growth factor-I treated animals was 31% and 29% faster (p <
      0.001) than 4.0 microg/cm(2) and 40.0 microg/cm(2) platelet-derived growth factor
      BB treated animals, respectively. Wounds treated with 4.0 microg/cm(2) platelet
      derived growth factor-BB/insulin-like growth factor-I healed, on average, in 22
      days compared with 31 days for 40.0 microg/cm(2) platelet-derived growth factor
      BB alone and 38 days for vehicle. Also, platelet-derived growth factor-BB/insulin
      like growth factor-I significantly improved the rate of wound closure throughout
      the duration of the studies compared with either dose of platelet-derived growth
      factor-BB alone (p < 0.005) or vehicle (p < 0.001). In conclusion, the data show
      that the combination of platelet-derived growth factor-BB and insulin-like growth
      factor-I is more effective than platelet-derived growth factor-BB alone at the
      doses tested or vehicle treatment in stimulating cutaneous wound healing in
      older, diabetic mice.

PMID- 17173562
TI  - Assessment of full-thickness wounds in the genetically diabetic mouse for
      suitability as a wound healing model.
AB  - While using the diabetic C57BL/KsJ db/db mouse as a wound healing model, we
      encountered several repair patterns which affect its suitability as a predictive
      screening model for certain indications. For example, wound contraction, albeit
      impaired, was found to be particularly dependent on bandaging technique and
      vehicle type. Wounds which had been continuously occluded with Opsite dressings
      had a high relative variability in contraction, and there was a tendency toward
      reduced contraction, suggesting that the dressings were acting as a splint.
      Viscous dosing vehicles inhibited contraction of occluded wounds but appeared to
      enhance contraction of nonoccluded wounds. In contrast to many other models,
      occlusion in these studies did not enhance reepithelialization when compared with
      air exposure (the rate of reepithelialization in db/db mice appeared normal,
      typically growing 2 mm from each edge in 10 days). Also in contrast to other
      wound healing models, viscous dosing vehicles when used under occlusion inhibited
      reepithelialization. However, as seen in other wound healing models, granulation
      tissue thickness was reliably increased in response to treatment with recombinant
      human platelet-derived growth factor-BB. Our experience with the db/db diabetic
      mouse model has led us to recommend the use of this animal model only after its
      limitations have been identified and accepted.

PMID- 17173564
TI  - The shrinking world: skin considerations in a global community.

PMID- 17173566
TI  - Laser treatment for pigmented lesions: a review.
AB  - BACKGROUND: Just a few decades ago, before lasers were introduced into
      dermatologic practice, many cutaneous lesions were untreatable. Since the
      introduction of lasers in dermatology in the 1960s and its revolution by Anderson
      and Parrish in the 1980s based on the selective photothermolysis theory, lasers
      have become a main component of many dermatology practices. With the advent of
      these selective lasers and their constant technological advancements, many
      lesions can now be easily removed with a low incidence of complications, creating
      a high demand for laser surgery. Aims This paper will review current laser
      systems used for pigmented lesions. METHODS: An English-language literature
      search and review through Medline from January 1994 to October 2004. Review of
      the latest techniques and lasers used in treating pigmentary disorders and
      possible future applications and treatment options. CONCLUSIONS: Laser technique
      and technology has greatly advanced producing more effacious treatment with
      minimal complications.

PMID- 17173565
TI  - Skin climacteric aging and hormone replacement therapy.
AB  - A gender perspective is indispensable for a full understanding of aging.
      Menopause is a turning point in women's lives. In addition to the effects of
      chronological aging, sunlight exposure, and other environmental and endogenous
      stimuli, the climacteric appears to exert some dramatic consequences on skin
      biology and aspect. The epidermis may become xerotic and exhibit altered
      functions. The dermis thins out and its elasticity decreases in concert with the
      decline in bone mass. The skin microcirculation is impaired. These aspects are
      some of the better worked-out changes of the climacteric, which in turn seem to
      be stabilized or in part reversible with hormone replacement therapy (HRT). The
      HRT effect on menopause consequences on hair growth and sebum production is less
      impressive. This review summarizes some important impacts of the climacteric on
      skin, and highlights the benefits of HRT that may influence cosmetic dermatology.

PMID- 17173567
TI  - Lasers for scars: a review.
AB  - Many articles have been published on improving the appearance of scars; however,
      there are no definitive management protocols. Our objective was to review the
      literature on laser therapy for various types of scars. There are multiple laser
      modalities that have been studied with certain features that may be indicated for
      specific scar types. Suggestions are given for further studies.

PMID- 17173568
TI  - An evaluation of a polyhydroxy acid skin care regimen in combination with azelaic
      acid 15% gel in rosacea patients.

PMID- 17173570
TI  - Sun-safety behaviors of skiers and snowboarders on the South Island of New
      Zealand.
AB  - AIMS: To study sun-protective behaviors among skiers and snowboarders on the
      South Island of New Zealand and to identify associations with personal
      characteristics or weather conditions. METHODS: Two hundred twenty-six skiers and
      snowboarders completed an interviewer-administered questionnaire during September
      and October 2002. Reported behaviors were used to derive a composite sun
      protection index, which was used to divide the sample into "protected" and
      "unprotected" groups. Odds ratios of being unprotected were calculated by
      logistic regression. RESULTS: Forty-eight percent (95% CI 42-54%) of interviewees
      recalled being sunburned while skiing or snowboarding in the past. Sixty-eight
      percent (95% CI 62-74%) were unaware of any educational messages specific to sun
      protection while skiing or snowboarding. Women were more likely to be protected
      from the sun (OR 0.47; 95% CI 0.27-0.81). Having a skin type resistant to burning
      (OR 1.93; 95% CI 0.92-4.06) and reported awareness of education messages (OR
      1.66; 95% CI 0.92-2.99) were associated with not using sun protection.
      CONCLUSIONS: Sunburn is common and sun protection not used by all. Men are less
      likely to report use of sun-protection measures. There is no evidence from this
      study that current strategies are effective in promoting skin protection while
      skiing or snowboarding.

PMID- 17173569
TI  - Anti-inflammatory effects of CoQ10 and colorless carotenoids.
AB  - BACKGROUND: CoQ10 (ubiquinone, coenzyme Q10) and carotenoids are popular
      antioxidants used in many skin care products to protect the skin from free
      radical damage. AIM: To evaluate the effects of CoQ10 and colorless carotenoids
      on the production of inflammatory mediators in human dermal fibroblasts treated
      with UV radiation (UVR) and to investigate the possible synergistic effects of
      these two antioxidants. METHODS: Normal human dermal fibroblast cell cultures
      were exposed to either 50 mJ of UVR or to IL-1 and then incubated with various
      concentrations of either CoQ10, the colorless carotenoids, phytoene and
      phytofluene, or to combinations of these antioxidants. After 24 h in culture,
      cells and spent medium were harvested and assayed by enzyme-linked immunosorbent
      assay for prostaglandin E2 (PGE-2), interleukin 6 (IL-6), and matrix
      metalloproteinase 1 (MMP-1). In addition, the ability of the carotenoids to
      protect CoQ10 from oxidation by the reactive oxygen species (ROS), hyperchlorite,
      was also determined. RESULTS: Human fibroblasts respond to UVR or to IL-1 by
      increasing the production of various inflammatory mediators including PGE-2, IL
      1, and IL-6 and proteases such as collagenase (MMP-1). Treatment of fibroblasts
      with 10 microm of CoQ10 suppressed the UVR- or IL-1-induced increase in PGE-2, IL
      6, and MMP-1. The combination of carotenoids and CoQ10 produced an enhanced
      inhibition of these three inflammatory mediators. Furthermore, the colorless
      carotenoids, phytoene and phytofluene, protected CoQ10 from degradation by the
      ROS, hypochlorite. CONCLUSION: CoQ10 is able to suppress the UVR- or IL-1-induced
      inflammatory response in dermal fibroblasts. Furthermore, this compound can block
      the UVR induction of the matrix-eroding enzyme, MMP-1. Finally, the combination
      of carotenoids plus CoQ10 results in enhanced suppression of inflammation. The
      results suggest that the combination of carotenoids and CoQ10 in topical skin
      care products may provide enhanced protection from inflammation and premature
      aging caused by sun exposure.

PMID- 17173571
TI  - Postacne scarring--a quantitative global scarring grading system.
AB  - BACKGROUND: There is no global quantitative grading system for assessing the
      disease load and global severity of disease in a patient with postacne scarring.
      AIMS: The purpose of this article is to provide a quantitative grading system
      that would allow more objective communication between practitioners of a
      patient's global disease severity and between investigators, educators, and
      proceduralists of the efficacy of grade-specific operative interventions or
      therapies. PATIENTS/METHODS: We describe a global scoring system that we have
      found clinically useful to assess disease load and severity of acne scarring and
      illustrate the reproducibility of this system in a small prospective study.
      Photographs of 21 patients were assessed independently by four observers, two of
      whom were physicians and the other two nurses. RESULTS: A quantitative global
      acne scarring grading system is presented. No substantial difference among acne
      scarring scores was seen between observers, with inter-rater agreement within
      four score points in 19 of the 21 patient-photos assessed. CONCLUSIONS: A global
      acne scarring grading system is presented that would allow investigators,
      educators, and proceduralists to compare their cases more accurately and to have
      a more objective discussion of the efficacy of operative interventions or
      therapies. This scoring system is shown to be reproducible among observers
      independent of medical background, suggesting that patients can be assigned
      scores equally by physicians and nurses.

PMID- 17173572
TI  - Percutaneous absorption of organic sunscreens.
AB  - The increased awareness of protection against skin cancer has led to a rise in
      the use of topically applied chemical sunscreen agents. There is a concern about
      the systemic absorption of organic filters in sunscreen formulations. The present
      study briefly reviews theoretical models for the prediction of the percutaneous
      penetration of the organic molecules and the accepted methods for the in vitro
      and in vivo evaluations of the penetration. The influence of the vehicle and the
      formulation viscosity on the penetration of sunscreens are examined. The
      development of novel methods for the minimization of sunscreen absorption is also
      discussed.

PMID- 17173573
TI  - Glabellar pomade crust mimicking dyskeratosis follicularis.
AB  - A 79-year-old female patient presented with a slowly developing crusting, itching
      verrucous lesion of the forehead of 3 months' duration. She had no personal or
      family history of skin disease. On examination she presented with a
      hyperpigmented plaque of the glabellar region that resembled dyskeratosis
      follicularis Darier. A detailed medical history was taken and a skin biopsy was
      performed. Epidermal acanthosis and enlargement of follicle ostia with foreign
      material were found. The patient reported use of an ointment twice daily. She had
      a single cosmetic treatment where powder of unspecified composition had been
      used. The diagnosis of pomade crust was confirmed. Follicular material was
      enucleated mechanically and the area was treated with a metronidazole cream. The
      lesions completely disappeared.

PMID- 17173574
TI  - Beyond skin feel: innovative methods for developing complex sensory profiles with
      silicones.
AB  - In today's competitive skin care market, formulators strive to meet consumer
      demand for products that combine performance with superior esthetics. Although
      skin feel has always been a key esthetic parameter, consumers increasingly select
      products based on a more complete sensory experience, including texture, scent,
      visual esthetics in the container, tactile effects on application, and the
      performance of active ingredients such as vitamins or sunscreen. This paper
      reviews approaches employed by Dow Corning which, when combined with sensory
      evaluation and formulation expertise, can be used to develop a more complete
      sensory experience, respond to consumer trends, or meet specific regional
      preferences for skin care products. It also describes how silicones can be used
      to develop new product appearance, texture, skin appearance, and feel, based on
      the wide range of rheological behavior and product forms among these materials.

PMID- 17173575
TI  - Nonablative radiofrequency for facial and neck rejuvenation. A faster, safer, and
      less painful procedure based on concentrating the heat in key areas: the
      ThermaLift concept.
AB  - Nonablative radiofrequency was the first method of noninvasive tissue
      contraction. It is a safe and effective method, although the results are modest
      when compared with plastic surgery. Patients like the fact that it requires no
      down time, it is performed with topical anesthesia, and it can be combined with
      numerous other modalities of skin rejuvenation. Technique and results are
      discussed.

PMID- 17173576
TI  - Do cosmetics cause airway allergy?

PMID- 17173577
TI  - An experimental critique on the state of knowledge of rosacea.

PMID- 17173578
TI  - Hirsutism, postpartum telogen effluvium, and male pattern alopecia.
AB  - This paper reviews the interrelating factors affecting hair growth. It presents
      current data on the development of alopecia and hirsutism in males and females
      and the newer approaches to treatment.

PMID- 17173579
TI  - Phototherapy in anti-aging and its photobiologic basics: a new approach to skin
      rejuvenation.
AB  - Intrinsic aging and photoaging of the face are constantly ongoing, and eventually
      result in the typical "aged" face, with visible lines and wrinkles at rest, a
      variety of dyschromia and a tired, dull and lax epidermis over poorly organized
      elastotic dermal architecture characterized by many interfibrillary spaces. Both
      ablative and nonablative resurfacing have been reported as solutions, the former
      providing excellent results, but a long patient downtime, and the latter giving
      little or no downtime, but less-than-ideal results. In ablative resurfacing, the
      epidermis is removed and replaced with a "new" epidermis, whereas in the
      nonablative approach the epidermis is spared through some form of cooling. In
      both approaches, however, the goal is to create controlled amounts of thermal
      damage in the dermis to stimulate the wound healing process, thus generating a
      tighter, better organized, "younger" dermal matrix. A better approach might be to
      apply prevention, rather than the cure, and to treat subjects in their very early
      20s, before even fine lines have begun to appear. This "photoanti-aging" approach
      could be achieved with the use of very low incident levels of photon energy to
      stimulate the skin cells, both epidermal and dermal, at cell-specific wavelengths
      based on the photobiological findings of the literature over the past two decades
      or so, in order to increase their resistance to the effects of chronological and
      photoaging. Lasers and IPL systems could be used, but are extremely expensive and
      therapist-intensive. A new generation of light-emitting diodes (LEDs) has
      appeared as the result of a spin-off from the US NASA Space Medicine Program,
      which are much more powerful than the previous generation with quasimonochromatic
      outputs. These LEDs can offer target specificity to achieve photobiomodulated
      enhanced action potentials of the skin cells, in particular mast cells,
      macrophages, endotheliocytes, and fibroblasts, plus increases in local blood and
      lymphatic flow, in a noninvasive, athermal manner. New phototherapeutic LED-based
      systems have appeared to meet the need for a less-expensive but clinically useful
      light source to enable photoantiaging as a reality in clinical practice. Some
      studies proving the efficacy of LED therapy have already appeared, and based on
      their results LED therapy represents a potential new approach to prevention in
      anti-aging, so that further studies are warranted to prove its efficacy.

PMID- 17173580
TI  - Onychocosmeceuticals.
AB  - The nail is the largest skin appendage. In addition to its important
      physiological and sensory functions, it is also of great esthetic importance.
      Complaints of brittle or soft nails are frequent, particularly among women.
      Innumerable preparations claiming to improve the nail quality are being sold;
      however, most have no proven beneficial effect. Also, surgery cannot enhance nail
      quality but improve shape and size abnormalities.

PMID- 17173581
TI  - Is the paper journal obsolete?

PMID- 17173582
TI  - Legal considerations in cosmetic laser surgery.
AB  - Cosmetic laser surgery is a continuously evolving field of medicine. According to
      the American Society for Dermatologic Surgery, over 100 million laser and light
      source cosmetic procedures were performed by its members. Procedures including
      hair removal, nonablative treatments, as well as removal of pigmented lesions,
      tattoos, and unwanted vascular lesions have revolutionized this field. With an
      increasing number of physicians and nonphysicians performing these procedures,
      and with the availability of increasingly powerful laser technologies, the
      potential for problems and their legal consequences continue to increase. This
      chapter will deal with the concept of negligence and the potential for a
      resultant medical malpractice that may arise in such a setting. An understanding
      of the basic principles of a cause of action in medical malpractice will likely
      protect a physician from losing such a case in a court of law.

PMID- 17173583
TI  - Nonablative lasers.
AB  - The trend toward minimally invasive rejuvenation techniques has led to the
      widespread use of nonablative lasers. Nonablative lasers can be classified in two
      groups based on their wavelengths: lasers emitting light in the visible range,
      and those emitting in the infrared range. In this review, different laser and
      intense pulsed light (IPL) systems are presented and critically discussed along
      with findings of the studies in the literature.

PMID- 17173584
TI  - Photoepilation: a potential threat to wound healing in a mouse.
AB  - BACKGROUND: Theoretically, the bulge area which is known to be a reservoir of
      epidermal stem cells should be destroyed to achieve permanent photoepilation. We
      wished to determine whether wound healing capability is perturbed after
      photoepilation. METHODS: Twenty C57/BL6 mice were used. After wax epilation to
      synchronize the hair cycle, one-half of the backs of mice were photoepilated in
      the early anagen stage. After the two hair cycles of the mice to confirm the hair
      removal effect, 30% trichloroacetic acid was applied to the both halves of the
      backs of the mice. A skin biopsy was performed on both sides before and just
      after the injury, and 2, 6, 9, and 14 days thereafter. The specimens were
      evaluated histologically after staining with hematoxylin and eosin, Masson
      trichrome, and Verhoeff-van Gieson. RESULTS: No differences in wound healing
      times were evident upon gross observation by the naked eye. However, the
      photoepilated hairless skin was observed to have a thicker epidermis and dermis
      than normal hairy skin by histological evaluation. The cellularity of the healed
      wound was much denser in the photoepilated. Collagen production of the neodermis
      in the normal hairy skin was first observed around the lower part of hair
      follicle, while it started from the upper papillary dermis in photoepilated skin.
      CONCLUSION: Photoepilation may disturb the normal wound healing process,
      especially dermal wound healing, and increases the risk of producing hypertropic
      scar or keloid.

PMID- 17173585
TI  - Combination of chemical peelings with botulinum toxin injections and dermal
      fillers.
AB  - BACKGROUND: Chemical peelings are one of the most powerful and diverse tools for
      skin rejuvenation. Depending on the chemical used, peelings are classified as
      superficial, medium, and deep. The depth of the peeling must be adjusted to the
      depth of the pathological process to be corrected. Deeper peels can eliminate
      pigmentary spots and wrinkles but are associated with longer recovery time.
      Chemical peels can be used in conjunction with other nonsurgical methods for skin
      rejuvenation such as botulinum toxin A (BTX-A) and dermal fillers. Surprisingly,
      descriptions of such combinations are rare in the current medical literature.
      AIMS: To review and describe our experience with a combination of chemical peels
      with other nonsurgical procedures for facial skin rejuvenation, such as BTX-A
      injections and dermal fillers. PATIENTS: Patients who came to the clinic for
      cosmetic treatments were assessed clinically and photographically to follow up
      the facial skin improvement following combination treatments. RESULTS AND
      CONCLUSIONS: By combining chemical peels with dermal fillers and BTX-A injections
      synergistic beneficial effect is achieved. These rejuvenating procedures
      significantly increase the satisfaction rate of our patients and are relatively
      easy to adopt by any practicing dermatologist.

PMID- 17173586
TI  - Employing a teaching module improves patient satisfaction in facial rejuvenation.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether a
      teaching module for facial rejuvenation improved patient satisfaction and
      enhanced practice growth in a cosmetic surgery office. An educational module was
      designed to review soft-tissue anatomy and physiology, treatment options, and
      outcomes. MATERIALS AND METHODS: During the initial office consultation, the
      module was utilized in group A (50 patients) but not in group B (50 patients).
      Satisfaction surveys were taken from all patients following the consultation.
      Patients from both groups who scheduled procedures were surveyed following
      completion of treatment. RESULTS: The surveys indicated a statistically
      significant higher level of satisfaction with the consultation, a better
      understanding of treatment options, and a greater percentage of treatment
      scheduling in group A patients (P < 0.05). Furthermore, patients in group A who
      underwent treatment indicated greater satisfaction with treatment outcome when
      compared to those treated patients in group B (P < 0.05). CONCLUSIONS: We
      conclude that use of a well-designed teaching module helps patients better
      understand the concepts behind facial rejuvenation and leads to increased
      procedure scheduling and greater patient satisfaction following treatment.

PMID- 17173587
TI  - A note on integumental (1-->3)(1-->6)beta-D-glucan permeation, using the porcine
      ear skin model.
AB  - Based on carbohydrate histochemical methods and the porcine ear skin model, the
      study demonstrates the rapid permeation of (1-->3)(1-->6)beta-d-glucans from a
      cosmetic formulation into the mammalian epidermis.

PMID- 17173589
TI  - Atopic xerosis: employment of noninvasive biophysical instrumentation for the
      functional analyses of the mildly abnormal stratum corneum and for the efficacy
      assessment of skin care products.
AB  - The subtle dryness of the skin surrounding the lesions of atopic dermatitis (AD)
      is called atopic dry skin or atopic xerosis (AX). AX is more susceptible to the
      development of AD skin lesions under various environmental stimuli than the
      clinically normal skin of the people who have or have had or will have AD, which
      might be called normal atopic skin (NAS) that shows no functional differences as
      compared to the skin of normal individuals. Routine histopathologic studies of AX
      that involve the invasive procedures of biopsy are not so helpful in clarifying
      the underlying pathogenesis. Modern, noninvasive biophysical instrumentation
      provides rich and quantitative information about various functional aspects of
      skin. The stratum corneum (SC) of AX reveals not only decreased hydration but
      also mildly impaired barrier function demonstrable as an increase in
      transepidermal water loss, elevated pH values, and an increased turnover rate of
      the SC consisting of thick layers of smaller-sized corneocytes. These data
      suggest that AX is related to mildly increased epidermal proliferation as a
      result of the presence of subclinical cutaneous inflammation. Although AX skin
      does not display any impairment in the recovery of barrier function after
      physical skin irritation by tape-stripping, it produces a much more severe, long
      lasting inflammatory response together with a delay in barrier repair after
      chemical irritation such as that induced by sodium lauryl sulphate. The SC of AX
      is biochemically characterized by reduction in the amounts of ceramides,
      especially ceramide I, sebum lipids, and water-soluble amino acids. None of these
      changes in SC functions are seen in NAS, which includes not only the normal
      looking skin of AD patients long after regression of all active lesions but also
      of latent atopic skin such as neonates who later develop AD. This suggests that
      all of the observed functional as well as biochemical abnormalities of AX are a
      reflection of subclinical inflammation. The presence of the underlying
      inflammation in AX also differentiates it from senile xerosis. The mildly
      impaired SC functions of AX can be improved by daily repeated applications of
      effective moisturizers, i.e., corneotherapy, which is effective in preventing the
      exacerbating progression of AX to AD resulting from inadvertent scratching of the
      skin that facilitates the penetration of environmental allergens into the skin.
      The biophysical confirmation of such efficacy of moisturizers, including cosmetic
      bases on the mildly impaired barrier function and decreased water-holding
      capacity of the SC of AX, definitely substantiates the importance of skin care
      for the cosmetic skin problems that affect every individual in the cold and dry
      season ranging from late autumn to early spring.

PMID- 17173588
TI  - Treatment of periungual vitiligo with erbium-YAG-laser plus 5-flurouracil: a left
      to right comparative study.
AB  - Despite the multiple treatment modalities available for vitiligo, none of them
      gives satisfactory results in the periungual type. In this study we tried to
      explore and evaluate the effects of the combination treatment of erbium:YAG laser
      resurfacing and topical 5-flurouracil in periungual vitiligo. Nine adult patients
      presenting with periungual vitiligo lesions were included in this prospective
      left-right comparative study. The desirable inflammation was achieved after a
      mean of 4.7 days of 5-flurouracil application. The mean re-epithelization time in
      the treatment sessions was 11.3 days. The patients received a mean of 3.4
      sessions in a mean duration of 7.6 months. The mean overall response to therapy
      in the treated group was 47.8% while in the control group it was 1.1% (P <
      0.0001). No side effects necessitated the stoppage of treatment. This study
      points to the efficacy and safety of this combination in the treatment of
      periungual vitiligo.

PMID- 17173590
TI  - An immunohistological study of anhydrous topical ascorbic acid compositions on ex
      vivo human skin.
AB  - BACKGROUND: Ascorbic acid has numerous essential and beneficial functions in
      normal and photoaged skin. Ionisation of ascorbic acid in aqueous topical
      formulations leads to oxidative degradation. Ascorbic acid in an anhydrous
      vehicle would inherently have greater stability. OBJECTIVE: The objective of this
      study was to observe the effects of two anhydrous formulations containing
      microfine particles of ascorbic acid on neocollagenesis and cytokeratin
      production in ex vivo human skin. METHODS: Vitamin C preparations were applied
      topically onto the surface of freshly excised human abdominal skin. Following an
      exposure time of 48 h with appropriate controls, skin discs were cut into
      sections, placed on slides and assessed using immunohistochemical (antibodies:
      collagen type I, III, cytokeratin) staining. Analysis was performed using
      microscopy and descriptive rating. RESULTS: Both formulations resulted in
      increased production of collagen types I and III and cytokeratin. CONCLUSION: The
      application of anhydrous formulations containing microfine particles of ascorbic
      acid to ex vivo human skin in this study resulted in neocollagenesis and
      increased production of cytokeratin. This approach appears to enable biological
      effects of ascorbic acid in the skin using a vehicle which would provide it
      greater stability than an aqueous vehicle.

PMID- 17173591
TI  - Skin rejuvenation without a scalpel. I. Fillers.
AB  - Fillers are an important tool in the armamentarium of the physician combating
      aging phenomena. A wide variety of filler substances are now available that meet
      many, but by far not all, needs in aesthetic medicine. The most commonly used
      substances now are hyaluronic acid and collagen preparations that have slightly
      different indications, but collagen requires pre-use testing to rule out
      inflammatory complications. Poly-L-lactic acid has gained its place in the
      filling of adipose tissue wasting in HIV-infected patients. Autologous fat is
      easy to harvest and inject and has virtually no risk of adverse side effects.
      Permanent fillers may be of advantage but carry the risk of permanent adverse
      reactions. Skillful combination of different fillers as well as with botulinum
      toxin injections and other cosmetic procedures may give optimal results.

PMID- 17173592
TI  - The safety of hydroquinone.

PMID- 17173593
TI  - Botulinum toxin in dermatology - beyond wrinkles and sweat.

PMID- 17173594
TI  - Pigmentary demarcation lines associated with pregnancy.

PMID- 17173595
TI  - Onychomycosis: beyond cosmetic distress.
AB  - Onychomycosis, or fungal infection of the nail, is the most common nail disease
      affecting children (although to a lesser extent) as well as adults. The distress
      it provokes is not only of a cosmetic kind; it may impair the quality of life.
      The different clinical types of onychomycosis should be differentiated from
      similar-looking nail diseases. As far as therapy is concerned, the appearance of
      new antifungal drugs in the 1990s makes our job easier, but it does not allow us
      to cure 100% of the patients. Relapses still exist. The aim of this article is to
      help dermatologists achieve a tailor-made treatment for their patients. The
      clinical type, the compulsory mycological investigations, the age of the patient,
      his medical history (drug intake), as well as the use of nail cosmetics, must be
      considered.

PMID- 17173596
TI  - The IVth IACD Congress - a holistic perspective.

PMID- 17173597
TI  - Development of sonic technology for the daily cleansing of the skin.
AB  - Even though many skin cleansing products are commercially available, the
      cleansing of the skin is dependent upon the user's diligence, compliance, and
      technique, which often results in inconsistent cleansing. When the skin is
      inadequately or excessively cleansed, the skin becomes compromised, sometimes
      leading to acute or chronic conditions that may require medical attention. A
      sonic skincare brush was developed to enhance and provide consistent skin
      cleansing while preventing the skin from becoming compromised. Utilizing a
      technology previously used to cleanse the oral cavity, the sonic skincare brush
      is optimized to work with the skin's own elasticity providing rapid oscillatory
      flexing of the infundibular opening. By oscillating at sonic speed the net result
      is the inelastic comedones become loosened and detached from the infundibular
      wall and are then cleared from the acroinfundibulum. Although additional clinical
      research into the various applications of sonic skin care technology is needed,
      utilization of sonic technology is now available for effectively and consistently
      cleansing the skin.

PMID- 17173598
TI  - The shape of beauty: determinants of female physical attractiveness.
AB  - Rarely has one research area gained as much attention as that which is observed
      for female physical attractiveness. The past decade has resulted in numerous,
      exciting developments, particularly with respect to three proposed determinants
      of beauty: waist to hip ratio (WHR), body mass index (BMI), and curvaceousness.
      The goal of our paper is to provide a highly necessary review of contemporary
      research on the female attractiveness, including an in-depth examination of these
      factors. In our review, we first discuss WHR, an index of fat deposition, which
      is calculated by measuring the circumference of the waist compared to the
      circumference of the hips. WHR is controlled by the sex hormones, and increases
      as women age, and hence, may influence perceptions of attractiveness. This factor
      has been hotly contested, as some researchers have claimed that a WHR of
      approximately 0.7 is universally most attractive, whereas others have found
      inconsistent findings, or suggest the importance of other factors, such as BMI.
      Body mass index (BMI), calculated by dividing the body weight (in kilograms) by
      height (in meters) squared, serves as a measure of body fat. Although WHR and BMI
      are correlated, they lead to different conclusions, and the importance of BMI as
      a measure of female attractiveness is debated in the literature. Similar to WHR
      research, BMI and its role in attractiveness is not cross-culturally consistent
      and is affected by the availability of resources within a given environment. It
      may be the case that both WHR and BMI influence female attractiveness. However,
      there has been little investigation of this possibility. We have explored this
      issue in our research, which revealed that both influence attractiveness, but in
      addition, we noticed that curvaceousness was also a factor. Curvaceousness is the
      degree of "hourglass" shape as determined, for example, by the size of the bust,
      relative to the circumference of the hips and waist, and the size of the
      buttocks. However, curvaceousness does not appear to be temporally stable as a
      marker of attractiveness, and it is not consistent across modes of presentation.
      For example, models in male-oriented magazines are more curvaceous than models in
      female-oriented magazines. In summary, faced with these recent findings, it is
      difficult to ascertain agreement among the various factors, especially when
      researchers investigate each determinant in isolation. We conclude that, although
      researchers have made many important initial steps in examining female
      attractiveness, there remains much to be discovered.

PMID- 17173599
TI  - Chronic pain as a disease in its own right.

PMID- 17173600
TI  - The role of pacemaker currents in neuropathic pain.
AB  - Hyperpolarization-activated cation nonselective cyclic nucleotide-gated (HCN)
      channels mediate pacemaker currents that control basic rhythmic processes
      including heartbeat. Alterations in HCN channel expression or function have been
      described in both epilepsy and cardiac arrhythmias. Recent evidence suggests that
      pacemaker currents may also play an important role in ectopic neuronal activity
      that manifests as neuropathic pain. Pacemaker currents are subject to endogenous
      regulation by cyclic nucleotides, pH and perhaps phosphorylation. In addition, a
      number of neuromodulators with known roles in pain affect current density and
      kinetics. The pharmacology of a number of drugs that are commonly used to treat
      neuropathic pain includes effects on pacemaker currents. Altered pacemaker
      currents in injured tissues may be an important mechanism underlying neuropathic
      pain, and drugs that modulate these currents may offer new therapeutic options.

PMID- 17173601
TI  - Side effects of antiepileptics--a review.
AB  - Older generation antiepileptic drugs like Phenobarbital (Luminal), carbamazepine
      (Tegretol), phenytoin (Dilantin), and valproic acid (Depakote) have several
      shortcomings such as suboptimal response rates, significant adverse effects,
      several drug interactions, and a narrow therapeutic index. New antiepileptic
      drugs have been developed in the last decade to overcome some of these problems.
      These newer generation antiepileptics like felbamate (Felbatol), gabapentin
      (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine
      (Trileptal), tiagabine (Gabitril), topiramate (Topamax), and zonisamide
      (Zonegran) have better tolerability profiles, low interaction potential, and
      significantly less enzyme inducing or inhibiting properties. As the use of
      antiepileptic drugs has expanded to include treatment of neuropathic pain, newer
      side effects have been reported. In addition to the common side effects of
      antiepileptic drugs, like dizziness, drowsiness, and mental slowing; other side
      effects like weight gain, metabolic acidosis, nephrolithiasis, angle closure
      glaucoma, skin rash, hepatotoxicity, colitis, and movement and behavioral
      disorders, to name a few, have been brought to our attention. This review is an
      attempt to highlight the features and incidences of some of these side effects.

PMID- 17173602
TI  - The psychological assessment of candidates for spinal cord stimulation for
      chronic pain management.
AB  - It is known that, in spite of meeting appropriate clinical criteria for spinal
      cord stimulation (SCS) and having undergone flawless procedures, a significant
      number of patients who fail the therapy continues to exist. It is the purpose of
      this article to focus on the development of psychosocial indicators of success
      for SCS, if any. Referring to specialist literature authors present a review of
      what is known, what is not known, and what remains controversial on this topic.
      After reading this article we hope the reader will understand the importance of a
      psychological evaluation as part of the development of standards for identifying
      appropriate patients for this therapy. To improve treatment outcomes of SCS,
      seems to be essential to perform psychosocial evaluations on all persons
      clinically indicated for SCS to exclude those patients, who most probably, on a
      psychosocial level, will fail the procedure. To maximize treatment efficacy,
      authors believe spinal cord stimulation for chronic pain control must be part of
      a comprehensive program. An accurate preoperative psychosocial assessment and a
      course of psychological assistance both before and after therapy seems to be
      crucial for improving outcomes.

PMID- 17173603
TI  - Outcome prediction following sympathetic block for complex regional pain
      syndrome.
AB  - Evidence for the efficacy of sympathetic blocks as either diagnostic or
      therapeutic tools in complex regional pain syndrome (CRPS) remains anecdotal.
      Systematic evaluation has been confounded by inconsistent terminology,
      difficulties in objectively quantifying physical findings, and failure to control
      for co-morbid psychological factors. This study examines the relative
      contribution of physical and psychometric features as prospective predictors of
      outcome following sympathetic block in the treatment of CRPS. Twenty patients
      with CRPS characterized by mechanical allodynia and vasomotor/sudomotor
      disturbance were treated with sympathetic blocks. Long-term outcome was assessed
      at > 6 months following the last treatment using a mailed questionnaire. Pain
      relief and functional improvement were negatively influenced by anxiety (P <
      0.001). When the improvement in the initial visual analog for pain (VAS) was 50%
      or greater following "diagnostic" sympathetic block, the percent improvement was
      highly correlated with improvement at long-term follow-up (P < 0.001). Higher
      "sensitivity" scores on the Neuropathic Pain Scale (P < 0.001), C fiber allodynia
      (P < 0.01) and Adelta-fiber allodynia (P < 0.01) on quantitative sensory testing,
      and pretreatment reported dynamic mechanical allodynia (P < 0.02) all predicted
      positive response to initial sympathetic block. While sympathetic blocks can be
      helpful in the reduction of mechanical allodynia, and thus the facilitation of
      physical and occupational therapy, ultimate response to a regime that includes
      medications is not predicted by sympathetic block alone.

PMID- 17173604
TI  - Treatment of chronic refractory intractable headache with botulinum toxin type a:
      a retrospective study.
AB  - Chronic refractory daily headache is a relatively common problem in the
      Australian population. Several million working hours per year are lost due to
      this illness. Generally not responding to conventional therapies. We treated 22
      such patients diagnosed as severe refractory migraine and/or mixed tension
      headache at our multidisciplinary pain management center. Before inclusion to our
      study, they received maximal medical management, which included cognitive
      behavior therapy, but failed to respond. These patients received between 30 and
      100 units of botulinum toxin type A. Our study showed 84% (19 of 22) achieved
      significant improvement in their pain complaint. There was significant reduction
      of medications particularly opioids. The duration of pain relief ranged from 1 to
      6 months. Repeat injections were necessary in several of the patients. There were
      minor complications but these reversed spontaneously without further treatment.

PMID- 17173605
TI  - Competency and certification of pain physicians.

PMID- 17173606
TI  - An unusual complication of sinus arrest following right-sided stellate ganglion
      block: a case report.
AB  - We present a case of a 29-year-old female patient who had presented to us for the
      management of her chronic right shoulder-hand pain and developed a sinus arrest
      following a right-sided stellate ganglion block (RSGB). This patient on receiving
      a diagnostic RSGB via the anterior paratracheal (C6) approach developed sinus
      arrest followed by apnea and unconsciousness. On institution of resuscitative
      measures involving tracheal intubation, positive pressure ventilation, cardiac
      massage, and intravenous atropine, spontaneous cardiac activity recovered in
      about 3 minutes. Other signs and symptoms resolved fully in a total of 10
      minutes. She had persistent postural hypotension lasting for about 24 hours
      requiring bed rest and was discharged about 36 hours after the procedure, without
      any adverse sequelae. As the sinus node is supplied by the right-sided
      sympathetic chain, its blockade probably resulted in unopposed parasympathetic
      activity leading to asystole. Available evidence of the role of right stellate
      ganglion in regulation of cardiac electrophysiology and functioning is also
      discussed.

PMID- 17173607
TI  - Whiplash associated disorders: pathomechanics, diagnosis, and management.
AB  - Whiplash has been defined as an injury mechanism, an injury, a medico-legal or
      social dilemma, and a complex chronic pain syndrome. Whiplash associated
      disorders are frequent in the cervical spine, especially as a result of a motor
      vehicle accident. The mechanisms responsible for whiplash-related tissue trauma
      are complex and a clinician's understanding of these complexities lends to a more
      complete appreciation for the anatomical structures and pathological processes
      that are involved, as well as a comprehensive diagnosis and appropriate
      management. While several classification scales have been developed for whiplash
      associated disorders, a thorough and tissue-specific examination is merited.
      Management should be directed toward pain reduction and normalization of
      mechanics. While conservative measures can address many of clinical sequelae of
      whiplash, both invasive pain management procedures and surgical interventions may
      be paramount to a patient's complete recovery.

PMID- 17173608
TI  - Efficacy of IDET for relief of leg pain associated with discogenic low back pain.
AB  - Intradiscal electrothermal annuloplasty (IDET) is an effective treatment for
      chronic discogenic low back pain (LBP). However, efficacy of IDET for the
      treatment of referred leg pain has not been examined. This study was performed to
      assess the long-term efficacy of IDET for the treatment of referred leg pain in
      chronic discogenic LBP patients. Data were retrospectively analyzed as an IDET
      case series from January 1999 to December 2000. The IDET procedure was performed
      at 1-3 symptomatic levels confirmed by pressure-controlled discography. General
      pain outcome was evaluated by Visual Analog Scale (VAS). LBP and leg pain were
      assessed separately using five-point pain scales (subsets of the North American
      Spine Society [NASS] LBP outcome assessment instrument: 0 = no pain, 4 = worst
      pain) at the 18-month follow-up. Among 129 patients who underwent IDET, 30
      patients underwent subsequent back surgery and were excluded from the study,
      giving a total of 99 patients. Eighty-three patients (83.8%) had leg pain without
      sciatica. Fifty-two (52.5%), 21 (21.2%), and 8 (8.0%) patients showed LBP > leg
      pain, LBP = leg pain and LBP < leg pain, respectively. Fifty-three out of 83
      patients (63.9%) showed post-IDET improvement in pain, with a mean VAS score of
      3.28 +/- 2.31. Thirty patients (36.1%) showed no improvement. A statistically
      significant (P < 0.05) improvement in subjective back and referred leg pain was
      observed. Improvements in back and referred leg pain were well-correlated (r =
      0.721, P < 0.01). A relatively large number of LBP patients who underwent IDET
      (84%) presented with referred leg pain without sciatica. The IDET procedure
      afforded improvements in leg pain that correlated well with improvements in back
      pain (0.75/4 and 0.88/4, respectively). These data suggest that IDET may relieve
      associated limb pain in chronic discogenic LBP patients.

PMID- 17173609
TI  - Are diagnostic lumbar facet injections influenced by pain of muscular origin?
AB  - INTRODUCTION: Nonradicular low back pain can be a difficult entity to accurately
      diagnose and treat. Facet joints, muscle, ligaments, and fascia have all been
      reported to be etiologies of acute and chronic low back pain. However, the facet
      joint as a source of low back pain is controversial. The diagnosis of facet joint
      pain is made by diagnostic facet joint or median nerve branch injections with a
      local anesthetic. The purpose of this study was to determine if the results of
      diagnostic facet joint injections are influenced by the technique used to perform
      these injections. METHODS: Seventy-five male patients aged 45 years or younger
      and 18 years or older who were injured while performing heavy work with
      nonradicular low back pain were included in this study. Diagnostic injection
      therapy was performed following Institutional Review Board approval and the
      patient's informed consent. Patients were assigned to one of five groups to
      receive diagnostic injections in a double-blinded fashion as follows: Group I:
      facet joint injection with continuous lidocaine administration from the skin to
      the facet joint as the needle was advanced; Group II: facet joint injection with
      saline administration from the skin to the facet joint as the needle was
      advanced; Group III: median nerve branch injection with a lidocaine advancing
      needle technique; Group IV: median nerve branch injection with saline advancing
      needle technique; and Group V: injection of the paraspinous muscles with local
      anesthetic and steroid following noted areas of pain diagnosed with saline
      injection and radiopaque contrast. After one week, the patients in Groups I to IV
      who had no pain relief with facet joint or median nerve block injections
      subsequently received paraspinous muscle injections, while the patients in Group
      V who had no long-term relief with muscle injections were given facet joint
      injections. The appropriate parametric and nonparametric tests were performed
      with statistical significance defined as P < or = 0.05. RESULTS: There were no
      differences among the groups demographically. The incidence of pain relief was
      significantly higher in subjects who had a continuous injection of local
      anesthetic into their musculature than in those individuals who received
      continuous saline followed by an injection of local anesthetic into their facet
      joint or median nerve branch. DISCUSSION: The results of this study demonstrated
      that local anesthetic injections are useful for the diagnosis of nonradicular low
      back pain but may yield false positive results with respect to lumbar facet pain
      depending upon the technique utilized.

PMID- 17173610
TI  - Divalproex ER prophylaxis in migraineurs with probable chronic migraine and
      probable medication-overuse headache: a case series.
AB  - This case series prospectively evaluated divalproex ER in 15 headache clinic
      migraine patients fulfilling International Headache Society criteria for probable
      chronic migraine and probable medication-overuse headache. Divalproex ER was
      initiated at 500 mg QHS and increased after Week 2 to 1000 mg QHS for a total
      treatment period of 2 months. Mean headache days per month dropped from 21.6 to
      10.4 at month 1 and 8.9 at month 2. All 10 patients who completed the study rated
      their satisfaction with treatment as changed from unsatisfied at baseline to
      satisfied at study completion. The results of this study support the prophylactic
      efficacy of divalproex ER in migraine patients with probable chronic migraine and
      probable medication-overuse headache.

PMID- 17173611
TI  - Treatment outcomes in spontaneous intracranial hypotension: do epidural blood
      patches stop the leaks?
AB  - Spontaneous intracranial hypotension (SIH) is a postural headache syndrome
      unrelated to dural puncture. Because of the increasing failure of epidural blood
      patch (EBP) to relieve headache in SIH, we retrospectively investigated the
      epidemiological features and treatment outcomes in 55 cases of SIH. The study
      population was stratified by age and sex; continuous variables were compared for
      differences by t-tests; categorical variables were compared by Chi-squared
      analysis or Fisher exact tests. Significant differences were identified by P
      values of 0.05 or less. The mean age of the study population was 44 +/- 12 years
      with a female to male ratio of 1.3:1.0. Men presented with subdural hematomas (P
      = 0.001) more often than women. Meningeal enhancement on contrast magnetic
      resonance imaging (MRI) was the most consistent radiographic finding.
      Radionuclide cisternography (RC) demonstrated thoracolumbar dural leaks in 16 of
      22 patients. EBP failures were more common in patients aged 40 and younger than
      in older patients (P = 0.003). Postural headache from SIH was not uniformly
      responsive to EBP, and had significant comorbidities, especially in men. The
      management of postural headache in SIH by other techniques to restore brain
      position and cerebrospinal fluid dynamics should be investigated.

PMID- 17173612
TI  - A management of early CRPS I caused by ankle sprain: a case report.
AB  - We present a case of a 13-year-old boy who developed signs and symptoms of
      neuropathic pain/early Complex Regional Pain Syndrome (CRPS) Type I, formerly
      known as Reflex Sympathetic Dystrophy (RSD), after spraining his ankle while
      wrestling. Aggressive pain control, using medications and sympatholytic blocks,
      with physical therapy and rehabilitation, led to the resolution of his painful
      condition. This prevented the disease from possibly progressing to a full-blown
      case of CRPS I (RSD) that is very challenging to treat.

PMID- 17173613
TI  - Anchoring of suboccipital lead: case report and technical note.
AB  - Suboccipital stimulation is a relatively new method of neuromodulation for
      treatment of intractable occipital headache and occipital neuralgia. The most
      common complication besides an infection is a lead displacement. Anchoring of a
      lead at the entry place partially solves the problem. Migration of electrode's
      tip is a major problem so far. A case report of electrode migration and a
      technique of retrograde lead insertion and subcutaneous anchoring of the tip by
      means of contralateral incision and suturing of lead is described.

PMID- 17173614
TI  - Transcutaneous application of pulsed radiofrequency: four case reports.
AB  - Pulsed radiofrequency is used for interventional therapy in many pain centers
      worldwide. A new, non-invasive method utilizing transcutaneous application
      appears to be effective in certain patients with chronic pain resistant to other
      therapies. The method is presented and four case reports are described.

PMID- 17173615
TI  - Gene stacking in transgenic plants--the challenge for 21st century plant
      biotechnology.
AB  - One of the major technical hurdles impeding the advance of plant genetic
      engineering and biotechnology is the fact that the expression or manipulation of
      multiple genes in plants is still difficult to achieve. Although a small
      proportion of commercial genetically modified (GM) crops present 'stacked' or
      'pyramided' traits, only a handful of products have been developed by introducing
      three or more novel genes. On the research front, a variety of conventional and
      more novel methods have been employed to introduce multiple genes into plants,
      but all techniques suffer from certain drawbacks. In this review, the potential
      and problems of these various techniques and strategies are discussed, and the
      prospects for improving these technologies in the future are presented.

PMID- 17173616
TI  - Modulation of F1 hybrid stature without altering parent plants through trans
      activated expression of a mutated rice GAI homologue.
AB  - Hybrid breeding, by taking advantage of heterosis, brings about many superior
      properties to the F1 progeny. However, some properties, such as increased plant
      height, are not desirable for agronomic purposes. To specifically counter the
      height increase associated with hybrid progeny, we employed an Arabidopsis model
      and tested a trans-activation system for specifically expressing a mutated GAI
      gene only in the F1 hybrid plants to reduce plant stature. A transcriptional
      activator, the Gal4 DNA-binding domain fused to the acidic activation domain of
      herpes simplex virus VP16 protein, driven by a maize ubiquitin promoter, was
      introduced in one parental line. A rice GAI homologue with an N-terminal deletion
      of the DELLA domain, driven by a promoter that is responsive to the
      transcriptional activator, was transferred into another parental line. After
      genetic crossing, trans-activation of the GAI mutant gene resulted in a dwarf
      phenotype. Over 50 pair-wise crosses between the parental lines were performed,
      and analyses suggested that the percentage of F1 progeny exhibiting dwarfism
      ranged from about 25% to 100%. Furthermore, the dwarfism trait introduced in F1
      progeny did not seem to affect total seed yield. Our result suggests the
      feasibility of manipulating F1 hybrid progeny traits without affecting parent
      plants or the agronomic property of the progeny.

PMID- 17173617
TI  - Metabolite fingerprinting in transgenic lettuce.
AB  - Metabolite fingerprinting has been achieved using direct atmospheric pressure
      chemical ionization-mass spectrometry (APCI-MS) and linked gas chromatography (GC
      APCI/EI-MS) for transgenic lettuce (Lactuca sativa L. cv. Evola) plants
      expressing an IPT gene under the control of the senescence-specific SAG12
      promoter from Arabidopsis thaliana (P(SAG12)-IPT). Mature heads of transgenic
      lettuce and their azygous controls were maintained under defined conditions to
      assess their shelf life. Transgenic lettuce plants exhibited delayed senescence
      and significant increases (up to a maximum of threefold) in the concentrations of
      three volatile organic compounds (VOCs), corresponding to molecular masses of 45,
      47 and 63, when compared with heads from azygous plants. These VOCs were
      identified as acetaldehyde (45), ethanol (47) and dimethyl sulphide (63). The
      increase in dimethyl sulphide was paralleled by an accumulation of reactive
      oxygen species (ROS) in the heads of transgenic plants. These results demonstrate
      the applicability of metabolic fingerprinting techniques to elucidate the
      underlying pleiotropic responses of plants to transgene expression.

PMID- 17173618
TI  - Global transcript profiling of potato tuber using LongSAGE.
AB  - Solanum tuberosum (potato) is the fourth major crop worldwide and is used for
      food, feed and biotechnological applications. To fully realize the biosynthetic
      potential for the production of starch, protein and metabolites, we conducted an
      extensive quantitative profiling of the expressed genes of mature potato tuber. A
      total of 58,322 serial analysis of gene expression (SAGE) tags of 19 nucleotides
      (nt), representing 22,233 different tags, were analysed. The 695 tags seen 10 or
      more times were assigned a tentative function by comparison with homologous
      genes. The identities of 12 'known' and 12 'unknown' transcripts were confirmed
      by rapid amplification of cDNA ends (RACE) cloning using the 19 nt tag as a
      primer. The SAGE and expressed sequence tag (EST) profiles of potato tuber were
      compared. Transcripts for four types of protease inhibitor, a metallothionein and
      a lipoxygenase were more prominent than patatin isoforms.

PMID- 17173619
TI  - Expression of the maize proteinase inhibitor (mpi) gene in rice plants enhances
      resistance against the striped stem borer (Chilo suppressalis): effects on larval
      growth and insect gut proteinases.
AB  - The maize proteinase inhibitor (mpi) gene was introduced into two elite japonica
      rice varieties. Both constitutive expression of the mpi gene driven by the maize
      ubiquitin 1 promoter and wound-inducible expression of the mpi gene driven by its
      own promoter resulted in the accumulation of MPI protein in the transgenic
      plants. No effect on plant phenotype was observed in mpi-expressing lines. The
      stability of transgene expression through successive generations of mpi rice
      lines (up to the T(4) generation) and the production of functional MPI protein
      were confirmed. Expression of the mpi gene in rice enhanced resistance to the
      striped stem borer (Chilo suppressalis), one of the most important pests of rice.
      In addition, transgenic mpi plants were evaluated in terms of their effects on
      the growth of C. suppressalis larvae and the insect digestive proteolytic system.
      An important dose-dependent reduction of larval weight of C. suppressalis larvae
      fed on mpi rice, compared with larvae fed on untransformed rice plants, was
      observed. Analysis of the digestive proteolytic activity from the gut of C.
      suppressalis demonstrated that larvae adapted to mpi transgene expression by
      increasing the complement of digestive proteolytic activity: the serine and
      cysteine endoproteinases as well as the exopeptidases leucine aminopeptidase and
      carboxypeptidases A and B. However, the induction of such proteolytic activity
      did not prevent the deleterious effects of MPI on larval growth. The introduction
      of the mpi gene into rice plants can thus be considered as a promising strategy
      to protect rice plants against striped stem borer.

PMID- 17173620
TI  - Agrobacterium-mediated RMCE approach for gene replacement.
AB  - We describe the site-directed integration (SDI) system for Agrobacterium-mediated
      transformation to precisely integrate a single copy of a desired gene into a
      predefined target locus by recombinase-mediated cassette exchange (RMCE). The
      system requires the selection of a transformed line with an integrated copy of a
      target cassette, and subsequent introduction of an exchange vector. The target
      cassette contains the npt and cod genes between oppositely orientated recognition
      sites (RS). The exchange vector T-DNA possesses an exchange cassette containing
      the gene of interest and a selectable marker gene, such as hpt, between
      oppositely orientated (inner) RS. Adjacent to the exchange cassette are ipt and
      recombinase (R) genes and an additional (outer) RS. The recombinase catalyses
      double-crossover between target RS and exchange inner RS to replace the
      integrated target cassette with the introduced exchange cassette. Transgenic
      plants that contain randomly integrated copies of the exchange vector T-DNA show
      an abnormal phenotype as a result of the overproduction of cytokinin from ipt
      gene expression. The recombinase can also act on the directly orientated outer RS
      to remove such randomly integrated copies. The system resulted in single-copy
      exchange into the target site only in regenerated tobacco at a frequency of 1%-3%
      per treated explant, or 4%-9% per regenerated line of normal phenotype. Thus,
      transgenic plants with only an exchanged copy can be efficiently accumulated and
      selected. Here, we show that the SDI system can efficiently replace the target
      cassettes with the exchange cassettes in a heterozygous or homozygous condition.
      The SDI system may be useful for precise comparisons of different gene
      constructs, the characterization of different chromosomal regions and the cost
      effective screening of reliable transgenic plants.

PMID- 17173621
TI  - Modification of gibberellin biosynthesis in the grafted apple scion allows
      control of tree height independent of the rootstock.
AB  - The availability of short stature apple scions that required minimal applications
      of chemical growth retardants and could be used with a range of rootstocks would
      be of considerable benefit to fruit growers. We have suppressed the expression of
      a gene encoding the gibberellin (GA) biosynthetic enzyme GA 20-oxidase to reduce
      the levels of bioactive GAs in a scion variety, resulting in significant
      reductions in stem height. Application of GA3 reversed the effect. The scion
      remained dwarfed after grafting on to normally invigorating rootstocks, whilst
      control plants of the same cultivar displayed the expected vigour when grafted on
      to these rootstocks. This approach could be applicable to any perennial crop
      variety, allowing dwarf trees to be obtained on any available rootstock or on
      their own roots without the need for chemical growth retardant application. In
      effect, seedlings that are well suited to local conditions (drought, salinity)
      could be employed as tree rootstocks, as could existing rootstocks valued for
      characters other than vigour control, such as pest and disease resistance.

PMID- 17173622
TI  - Transformation of maize with the p1 transcription factor directs production of
      silk maysin, a corn earworm resistance factor, in concordance with a hierarchy of
      floral organ pigmentation.
AB  - The maize p1 gene encodes an R2R3-MYB transcription factor that controls the
      biosynthesis of red flavonoid pigments in floral tissues of the maize plant.
      Genetic and quantitative trait locus analyses have also associated the p1 gene
      with the synthesis of maysin, a flavone glycoside from maize silks that confers
      natural resistance to corn earworm. Here, we show directly that the p1 gene
      induces maysin accumulation in silk tissues. Transformation of maize plants that
      had low or no silk maysin with p1 transgenes elevated silk maysin concentrations
      to levels sufficient for corn earworm abiosis. The p1 transgenes also conferred
      red pigment to pericarp, cob, husk and tassel tissues, as expected; however,
      different subsets of these tissues were pigmented within individual transgenic
      plants. Statistical analysis shows that the pigmentation patterns observed
      amongst the p1 transgenic plants conform to a hierarchy that is similar to the
      temporal ordering of floral organ initiation. We propose that the observed
      hierarchy of pigmentation patterns is conferred by variation due to epigenetic
      control of the p1 transgenes. The production of plants with improved traits
      through genetic engineering can depend in large part on the achievement of tight
      organ-specific expression of the introduced transgenes. Our results demonstrate
      that the production of transgenic plants using a promoter with well-defined
      tissue specificity, such as the p1 promoter, can result in unexpected variation
      in tissue specificity amongst the resulting transgenic plants.

PMID- 17173623
TI  - Immunomodulation of polyamine biosynthesis in tobacco plants has a significant
      impact on polyamine levels and generates a dwarf phenotype.
AB  - Ornithine decarboxylase (ODC) is a cytosolic enzyme that catalyses the direct
      decarboxylation of l-ornithine to putrescine, one of the rate-limiting steps of
      polyamine biosynthesis in plants. In the present study, an ODC-specific murine
      single-chain antibody fragment (scFvODC1) was generated by phage display
      technology. To evaluate the effect of the recombinant antibody fragment on ODC
      activity and polyamine levels, we produced transgenic tobacco plants that
      accumulated scFvODC1 in the cytosol. Expression levels of up to 4% total soluble
      protein (TSP) were achieved, resulting in the inhibition of up to 90% of
      endogenous ODC activity. A significant reduction in putrescine, spermidine and
      spermine levels was observed in transgenic lines producing high levels of
      scFvODC1. Furthermore, these lines showed developmental abnormalities and a dwarf
      phenotype. We show that the immunomodulation of enzyme activity is a powerful
      approach that can be used to alter complex and tightly controlled metabolic
      pathways, allowing specific steps in the pathway to be blocked and the resulting
      physiological effects to be investigated.

PMID- 17173624
TI  - Production of cyanophycin, a suitable source for the biodegradable polymer
      polyaspartate, in transgenic plants.
AB  - The production of biodegradable polymers in transgenic plants in order to replace
      petrochemical compounds is an important challenge for plant biotechnology.
      Polyaspartate, a biodegradable substitute for polycarboxylates, is the backbone
      of the cyanobacterial storage material cyanophycin. Cyanophycin, a copolymer of l
      aspartic acid and l-arginine, is produced via non-ribosomal polypeptide
      biosynthesis by the enzyme cyanophycin synthetase. A gene from
      Thermosynechococcus elongatus BP-1 encoding cyanophycin synthetase has been
      expressed constitutively in tobacco and potato. The presence of the transgene
      encoded messenger RNA (mRNA) correlated with changes in leaf morphology and
      decelerated growth. Such transgenic plants were found to produce up to 1.1% dry
      weight of a polymer with cyanophycin-like properties. Aggregated material, able
      to bind a specific cyanophycin antibody, was detected in the cytoplasm and the
      nucleus of the transgenic plants.

PMID- 17173625
TI  - Optimization of Agrobacterium-mediated transient assays of gene expression in
      lettuce, tomato and Arabidopsis.
AB  - Agrobacterium-mediated transient assays for gene function are increasingly being
      used as alternatives to genetic complementation and stable transformation.
      However, such assays are variable and not equally successful in different plant
      species. We analysed a range of genetic and physiological factors affecting
      transient expression following agroinfiltration, and developed a protocol for
      efficient and routine transient assays in several plant species. Lettuce
      exhibited high levels of transient expression and was at least as easy to work
      with as Nicotiana benthamiana. Transient expression occurred in the majority of
      cells within the infiltrated tissue and approached 100% in some regions. High
      levels of transient expression were obtained in some ecotypes of Arabidopsis;
      however, Arabidopsis remains recalcitrant to routine, genotype-independent
      transient assays. Transient expression levels often exceeded those observed in
      stably transformed plants. The laboratory Agrobacterium tumefaciens strain C58C1
      was the best strain for use in plant species that did not elicit a necrotic
      response to A. tumefaciens. A wild A. tumefaciens strain, 1D1246, was identified
      that provided high levels of transient expression in solanaceous plants without
      background necrosis, enabling routine transient assays in these species.

PMID- 17173626
TI  - Review: intellectual property aspects of plant transformation.
AB  - One of the recurring themes of the debates concerning the application of genetic
      transformation technology has been the role of Intellectual Property Rights
      (IPR). This term covers both the content of patents and the confidential
      expertise usually related to methodology and referred to as 'Trade Secrets'. This
      review explains the concepts behind patent protection, and discusses the wide
      ranging scope of existing patents that cover all aspects of transgenic
      technology, from selectable markers and novel promoters to methods of gene
      introduction. Although few of the patents in this area have any real commercial
      value, there are a small number of key patents that restrict the 'freedom to
      operate' of new companies seeking to exploit the methods. Over the last 20 years,
      these restrictions have forced extensive cross-licensing between ag-biotech
      companies and have been one of the driving forces behind the consolidation of
      these companies. Although such issues are often considered of little interest to
      the academic scientist working in the public sector, they are of great importance
      in any discussion of the role of 'public-good breeding' and of the relationship
      between the public and private sectors.

PMID- 17173627
TI  - Resistance to cassava mosaic disease in transgenic cassava expressing antisense
      RNAs targeting virus replication genes.
AB  - African cassava mosaic virus (ACMV) is a major contributor to cassava mosaic
      disease (CMD), the economically most important and devastating disease of cassava
      in Africa. We have developed transgenic cassava plants with increased ACMV
      resistance using improved antisense RNA technology by targeting the viral mRNAs
      of Rep (AC1), TrAP (AC2) and REn (AC3). Viral DNA replication assays in detached
      leaves demonstrated that replication of two ACMV isolates was strongly reduced or
      inhibited in most transgenic lines. After ACMV infection of plants using
      biolistic inoculation, several lines remained symptomless at lower infection
      pressure (100 ng viral DNA/plant). Symptom development was reduced and attenuated
      even at higher DNA doses. Transgenic ACMV-resistant plants had significantly
      reduced viral DNA accumulation in their infected leaves. Short sense and
      antisense RNAs specific to AC1 were identified in transgenic lines expressing AC1
      antisense RNA, suggesting that the short RNAs mediate interference by post
      transcriptional gene silencing. Our results demonstrate that resistance to ACMV
      infection of cassava can be achieved with high efficacy by expressing antisense
      RNAs against viral mRNAs encoding essential non-structural proteins, providing a
      new tool to combat CMD in Africa.

PMID- 17173628
TI  - Rapid generation of plant traits via regulation of DNA mismatch repair.
AB  - The reversible inhibition of DNA repair is a novel approach to maximize genetic
      diversity within a plant's genome in order to generate offspring exhibiting
      important de novo output traits. This process is based on the inhibition of the
      evolutionarily conserved mismatch repair (MMR) system. In this process, a human
      dominant negative MMR gene allele is introduced into the germline of a target
      plant, yielding progeny that can be screened to identify variants with
      commercially important agronomic output traits. Using this novel strategy, we
      generated MMR-deficient Arabidopsis thaliana plants that showed genome-wide
      instability of nucleotide repeats associated with chromosomal microsatellites, in
      addition to base substitution mutations. Functional screenings of the MMR
      deficient Arabidopsis offspring identified variants expressing selectable traits
      (ethylene insensitivity and salt tolerance), as well as plants exhibiting altered
      morphologic traits (albinos and dwarfs). We determined by segregation analyses of
      variant plants that the de novo phenotypes were due to both recessive and
      dominant genetic mutations. Mutations caused by MMR deficiency showed a different
      spectrum compared with those derived using ethylmethane sulphonate (EMS)
      mutagenesis. Our finding demonstrates the feasibility of using reversible MMR
      deficiency via transient expression of a single human gene product to enhance
      genetic diversity in plants.

PMID- 17173629
TI  - Manipulation of plant tolerance to herbicides through co-ordinated metabolic
      engineering of a detoxifying glutathione transferase and thiol cosubstrate.
AB  - The diphenyl ether herbicide fomesafen can be used selectively in soybean
      (Glycine max) due to its rapid detoxification by tau class glutathione
      transferases (GmGSTUs) which preferentially utilize the endogenous thiol
      homoglutathione (hGSH) as cosubstrate. Soybean cDNAs encoding GmGSTU21, which is
      highly active in detoxifying fomesafen, and an hGSH synthetase (GmhGS) have been
      cloned and functionally identified in Escherichia coli. Tobacco plants, which
      have limited GST activities towards fomesafen and which accumulate glutathione
      (GSH), rather than hGSH, have been transformed with either GmhGS alone, or a dual
      construct of GmhGS-GmGSTU21, both under the control of constitutive promoters.
      Using either construct, the transgenic tobacco accumulated hGSH, with a
      concomitant increase in GSH content. Segregating T1 plants were analysed for
      thiol content and GST activity towards fomesafen with GSH and hGSH as
      cosubstrates, and then scored for photobleaching injury caused by applications of
      fomesafen. These studies showed that hGSH accumulation alone gave no significant
      protection against the herbicide and that tolerance was only seen in plants which
      contained appreciable concentrations of hGSH and GmGSTU21 activity. Tolerance in
      the dual transformants was associated with the metabolism of radiolabelled
      fomesafen to inactive hGSH-derived conjugates, while susceptible lines were
      unable to detoxify the herbicide. These studies confirm the combined importance
      of specific GSTs and their preferred thiol cosubstrates in conferring herbicide
      selectivity traits in planta.

PMID- 17173630
TI  - The wheat Em promoter drives reporter gene expression in embryo and aleurone
      tissue of transgenic barley and rice.
AB  - The early methionine (Em) proteins are members of the late embryogenesis abundant
      (LEA) group of proteins that have been considered to be embryo specific. The
      ability of a 646-bp wheat Em promoter to control green fluorescent protein (gfp)
      expression was investigated in transgenic barley and rice. Seeds of transgenic
      plants expressed gfp in the developing embryo but also in the aleurone layer. The
      646-bp Em promoter also directed strong gfp expression in cells comprising the
      junction between the endosperm transfer cells and cells of the aleurone layer. Em
      gfp expression in transgenic barley showed differences in spatial and temporal
      control when compared with that observed in transgenic rice. Em-gfp expression
      was also detected in mature aleurone cells of transgenic barley and rice with and
      without abscisic acid (ABA) treatment. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) results indicated the presence of Em and Em-homologous
      transcript in embryo, aleurone and endosperm tissues of wheat and of barley and
      rice, respectively. These results suggest that Em proteins may be expressed in
      both the embryo and aleurone during seed development, possibly providing
      protection against desiccation in these two tissues that survive seed drying.
      They may also have a similar role in these tissues during germination. The Em
      promoter from wheat may be useful in the expression of novel genes in cereal
      grains, as an embryo- and aleurone-specific promoter complementing other
      available endosperm- and pericarp-specific promoters to collectively increase the
      expression of transgenes in seeds.

PMID- 17173631
TI  - A novel thiolase-reductase gene fusion promotes the production of
      polyhydroxybutyrate in Arabidopsis.
AB  - The production of polyhydroxybutyrate (PHB) involves a multigene pathway
      consisting of thiolase, reductase and synthase genes. In order to simplify this
      pathway for plant-based expression, a library of thiolase and reductase gene
      fusions was generated by randomly ligating a short core linker DNA sequence to
      create in-frame fusions between the thiolase and reductase genes. The resulting
      fusion constructs were screened for PHB formation in Escherichia coli. This
      screen identified a polymer-producing candidate in which the thiolase and
      reductase genes were fused via a 26-amino-acid linker. This gene fusion,
      designated phaA-phaB, represents an active gene fusion of two homotetrameric
      enzymes. Expression of phaA-phaB in E. coli and Arabidopsis yielded a fusion
      protein observed to be the expected size by Western blotting techniques. The
      fusion protein exhibited thiolase and reductase enzyme activities in crude
      extracts of recombinant E. coli that were three-fold and nine-fold less than
      those of the individually expressed thiolase and reductase enzymes, respectively.
      When targeted to the plastid, and coexpressed with a plastid-targeted
      polyhydroxyalkanoate (PHA) synthase, the fusion protein enabled PHB formation in
      Arabidopsis, yielding roughly half the PHB formed in plants expressing individual
      thiolase, reductase and synthase enzymes. This work represents a first step
      towards simplifying the expression of the PHB biosynthetic pathway in plants.

PMID- 17173632
TI  - Plant-derived mouse IgG monoclonal antibody fused to KDEL endoplasmic reticulum
      retention signal is N-glycosylated homogeneously throughout the plant with mostly
      high-mannose-type N-glycans.
AB  - Plants are potential hosts for the expression of recombinant glycoproteins
      intended for therapeutic purposes. However, N-glycans of mammalian glycoproteins
      produced in transgenic plants differ from their natural counterparts. The use of
      the endoplasmic reticulum (ER)-retention signal has been proposed to restrict
      glycosylation of plantibodies to only high-mannose-type N-glycans. Furthermore,
      little is known about the influence of plant development and growth conditions on
      N-linked glycosylation. Here, we report a detailed N-glycosylation profiling
      study of CB.Hep1, a mouse IgG2b monoclonal antibody (mAb) against hepatitis B
      surface antigen (HBsAg) currently expressed in tobacco plants (Nicotiana tabacum
      L.). The KDEL ER-retention signal was fused to the C-terminal of both light and
      heavy chains. The structures of the N-linked glycans of this mAb produced in
      transgenic tobacco plants at various growth stages were analysed by high
      performance liquid chromatography (HPLC) profiling techniques and matrix-assisted
      laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and
      compared with those of murine origin. The high-mannose-type oligosaccharides
      accounted for more than 80% of the total N-glycans, with Man7GlcNAc2 being the
      most abundant species. Some complex N-glycans bearing xylose and small amounts of
      oligosaccharides with both xylose and fucose were identified. No appreciable
      differences were detected when comparing glycosylation at different leaf ages,
      e.g. from seedling leaves up to 8 weeks old and top or basal leaves of mature
      plants, or between leaves, stems and whole plants. A strict retention of
      glycoproteins to ER by the use of the tetrapeptide KDEL was not sufficient, even
      though the majority of the resulting N-glycosylation was of the high-mannose
      type. It is highly likely to be dependent on other factors, which are most
      probably protein specific.

PMID- 17173633
TI  - Molecular genetics of fructan metabolism in perennial ryegrass.
AB  - Fructans are the main storage carbohydrates of temperate grasses, sustaining
      regrowth immediately after defoliation, as well as contributing to the nutritive
      value of feed. Fructan metabolism is based on the substrate sucrose and involves
      fructosyltransferases (FTs) for biosynthesis and fructan exohydrolases (FEHs) for
      degradation. Sucrose is also utilized by invertases (INVs), which hydrolyse it
      into its constituent monosaccharides for use in metabolism. The isolation,
      molecular characterization, functional analysis, and phylogenetic relationships
      of genes encoding FTs, FEHs, and INVs from temperate grasses are reviewed, with
      an emphasis on perennial ryegrass (Lolium perenne L.). The roles these enzymes
      play in fructan accumulation and remobilization, and future biotechnological
      applications in molecular plant breeding are discussed.

PMID- 17173634
TI  - Biodegradation of atrazine in transgenic plants expressing a modified bacterial
      atrazine chlorohydrolase (atzA) gene.
AB  - Atrazine is one of the most widely used herbicides in the USA. Atrazine
      chlorohydrolase (AtzA), the first enzyme in a six-step pathway leading to the
      mineralization of atrazine in Gram-negative soil bacteria, catalyses the
      hydrolytic dechlorination and detoxification of atrazine to hydroxyatrazine. In
      this study, we investigated the potential use of transgenic plants expressing
      atzA to take up, dechlorinate and detoxify atrazine. Alfalfa, Arabidopsis
      thaliana and tobacco were transformed with a modified bacterial atzA gene, p
      atzA, under the control of the cassava vein mosaic virus promoter. All transgenic
      plant species actively expressed p-atzA and grew over a wide range of atrazine
      concentrations. Thin layer chromatography analyses indicated that in planta
      expression of p-atzA resulted in the production of hydroxyatrazine.
      Hydroponically grown transgenic tobacco and alfalfa dechlorinated atrazine to
      hydroxyatrazine in leaves, stems and roots. Moreover, p-atzA was found to be
      useful as a conditional-positive selection system to isolate alfalfa and
      Arabidopsis transformants following Agrobacterium-mediated transformation. Our
      work suggests that the in planta expression of p-atzA may be useful for the
      development of plants for the phytoremediation of atrazine-contaminated soils and
      soil water, and as a marker gene to select for the integration of exogenous DNA
      into the plant genome.

PMID- 17173635
TI  - The production of synthetic chemodisruptive peptides in planta disrupts the
      establishment of cyst nematodes.
AB  - Root exudates from transgenic potato plants expressing a chemoreception
      disruptive peptide inhibit acetylcholinesterase by up to 63 +/- 3%. This
      inhibition correlates strongly with the efficacy of the exudates as a presoak
      solution for infective juveniles of Heterodera glycines that leads to reduced
      root invasion. The establishment of developing Globodera pallida at 21 days post
      infection in these transgenic plants was also suppressed in containment trials.
      Relative to controls, the best line showed a 47 +/- 5% reduction in developing
      females and had 188 +/- 25% more undeveloped infective juveniles. This suggests
      that disorientation of chemoreception occurs after initial root invasion. Line
      (e) showed the highest level of resistance with 61 +/- 4% in glasshouse trials
      conducted over a 9-week period. This result represents the combined effect on the
      number of cysts produced and the number of eggs each cyst contains. The level of
      control shown to saccate females was consistent in both the 21-day and 9-week
      post-infection studies. Another chemoreception-disruptive peptide, that binds to
      nematode nicotinic receptors in cholinergic neurones, provided a 52.6 +/- 1%
      reduction in the number of nematodes able to establish in transgenic hairy roots
      that expressed the peptide. This confirms that both chemoreception-disruptive
      peptides have efficacy in suppressing parasitism by cyst nematodes when expressed
      in planta at low concentrations.

PMID- 17173636
TI  - A functional antibody lacking N-linked glycans is efficiently folded, assembled
      and secreted by tobacco mesophyll protoplasts.
AB  - A potential drawback in the use of plants as an expression platform for
      pharmaceutical proteins such as antibodies is that plant-specific N-glycosylation
      can result in proteins with altered function and potential antigenicity. In many
      cases, the N-glycans are essential for the correct folding, assembly and
      transport of the recombinant proteins. We tested whether progressive removal of
      glycosylation sites had a detrimental effect on the synthesis, assembly and
      secretion of a plant-made immunoglobulin G, Guy's 13. Our results indicate that
      the plant secretory pathway can cope well with aglycosylated antibody chains. The
      immunoglobulin without N-linked glycans is correctly assembled and secreted by
      tobacco protoplasts. Capture enzyme-linked immunosorbent assay also shows that
      antigen-binding properties are unaffected. Our results therefore suggest one
      possible alternative to the engineering of a humanized glycosylation machinery in
      plants.

PMID- 17173637
TI  - Tuber on a chip: differential gene expression during potato tuber development.
AB  - Potato tuber development has proven to be a valuable model system for studying
      underground sink organ formation. Research on this topic has led to the
      identification of many genes involved in this complex process and has aided in
      the unravelling of the mechanisms underlying starch synthesis. However, less
      attention has been paid to the biochemical pathways of other important
      metabolites or to the changing metabolic fluxes occurring during potato tuber
      development. In this paper, we describe the construction of a potato
      complementary DNA (cDNA) microarray specifically designed for genes involved in
      processes related to tuber development and tuber quality traits. We present
      expression profiles of 1315 cDNAs during tuber development where the predominant
      profiles were strong up- and down-regulation. Gene expression profiles showing
      transient increases or decreases were less abundantly represented and followed
      more moderate changes, mainly during tuber initiation. In addition to the
      confirmation of gene expression patterns during tuber development, many novel
      differentially expressed genes were identified and are considered as candidate
      genes for direct involvement in potato tuber development. A detailed analysis of
      starch metabolism genes provided a unique overview of expression changes during
      tuber development. Characteristic expression profiles were often clearly
      different between gene family members. A link between differential gene
      expression during tuber development and potato tissue specificity is described.
      This dataset provides a firm basis for the identification of key regulatory genes
      in a number of metabolic pathways that may provide researchers with new tools to
      achieve breeding goals for use in industrial applications.

PMID- 17173638
TI  - Oral immunotherapy against a pollen allergy using a seed-based peptide vaccine.
AB  - Peptide immunotherapy using dominant T-cell epitopes is safer and more effective
      than conventional immunotherapy for the treatment of immunoglobulin E (IgE)
      mediated allergic diseases. When allergenic T-cell epitope peptides are expressed
      in the edible part of transgenic plants, successful mucosal immune tolerance to
      these allergens may be attainable by the consumption of these plants. In this
      study, we generated transgenic rice seed that accumulated high concentrations
      (about 60 microg per grain) of polypeptide consisting of seven dominant human T
      cell epitopes derived from the Japanese cedar pollen allergens, Cry j 1 and Cry j
      2, in the endosperm. Oral administration of these transgenic rice seeds to B10.S
      mice before or after they were immunized with Cry j 1 holoprotein reduced not
      only their T-cell proliferative response to Cry j 1, but also their serum IgE
      levels, proving the efficacy of oral immunotherapy for the treatment of
      pollinosis.

PMID- 17173639
TI  - Matrix attachment regions and regulated transcription increase and stabilize
      transgene expression.
AB  - Transgene silencing has been shown to be associated with strong promoters, but it
      is not known whether the propensity for silencing is caused by the level of
      transcription, or some other property of the promoter. If transcriptional
      activity fosters silencing, then transgenes with inducible promoters may be less
      susceptible to silencing. To test this idea, a doxycycline-inducible luciferase
      transgene was transformed into an NT1 tobacco suspension culture cell line that
      constitutively expressed the tetracycline repressor. The inducible luciferase
      gene was flanked by tobacco Rb7 matrix attachment regions (MAR) or spacer control
      sequences in order to test the effects of MARs in conjunction with regulated
      transcription. Transformed lines were grown under continuous doxycycline (CI), or
      delayed doxycycline induction (DI) conditions. Delayed induction resulted in
      higher luciferase expression initially, but continued growth in the presence of
      doxycycline resulted in a reduction of expression to levels similar to those
      found in continuously induced lines. In both DI and CI treatments, the Rb7 MAR
      significantly reduced the percentage of silenced lines and increased transgene
      expression levels. These data demonstrate that active transcription increases
      silencing, especially in the absence of the Rb7 MAR. Importantly, the Rb7 MAR
      lines showed higher expression levels under both CI and DI conditions and avoided
      silencing that may occur in the absence of active transcription such as what
      would be expected as a result of condensed chromatin spreading.

PMID- 17173640
TI  - The past, present, and future of wound healing.

PMID- 17173641
TI  - Fibroblast heterogeneity in the healing wound.
AB  - Although fibroblasts are traditionally described as static cells providing
      framework and support for tissues, there is an accumulating body of evidence
      showing that fibroblasts are a dynamic cell type which exist in functionally and
      morphologically heterogeneous subpopulations. Fibroblast subsets have been shown
      to play a critical role in the production and regulation of extracellular matrix
      components, in wound repair and regeneration, and have been implicated in the
      pathogenesis of fibrotic conditions. We have reviewed the evidence supporting
      heterogeneity of fibroblasts from pulmonary, periodontal, and dermal tissues. In
      addition, we will explore the role fibroblast subpopulations may play in the
      complex process of wound repair and regeneration.

PMID- 17173642
TI  - Experimental approaches to chronic wounds.
AB  - The pathogenesis of most chronic wounds is unknown. In this report, we summarize
      several areas of investigation which appear ready for further progress and which
      were discussed at a recent National Institutes of Health workshop on this
      subject. Of note were presentations of research on the role of fibrosis in wound
      healing, interaction of cytokines, hypoxia, extracellular matrix formation,
      keratinocyte migration, and involvement of proteases and neuropeptides in chronic
      wounds.

PMID- 17173643
TI  - Spatial and temporal expression of transforming growth factor-beta isoforms
      during ovine excisional and incisional wound repair.
AB  - To elucidate the role for transforming growth factor-beta isoforms (beta(1), 
      beta(2), and -beta(3)) in wound repair, we used isoform-specific antibodies to
      detect the spatial and temporal expression of the latent and mature/active
      transforming growth factor-beta isoforms by immunohistochemical localization
      through 21 days after excisional and incisional wounding of ovine skin. Although
      incisional and excisional wounds showed similar patterns of transforming growth
      factor-beta immunoreactivity, we found a differential temporal and spatial
      expression of the latent and mature transforming growth factor-beta isoforms
      throughout wound repair. Specifically, 1 day after wounding, there was a marked
      increase in transforming growth factor-beta isoforms in the epithelium adjacent
      to the wound, epidermal appendages, and the cells and matrix of the granulation
      tissue. At this time, transforming growth factor-beta(3) isoform was the most
      abundant. Most notably, the epidermis adjacent to the wound was intensely
      immunoreactive for all transforming growth factor-beta isoforms 1 day after
      injury. However, the migrating epithelium, derived from both the hair follicles
      and the wound margins, was completely devoid of immunoreactive transforming
      growth factor-beta until reepithelialization was complete. Within the
      inflammatory exudate, there was a distinct band of leukocytes that was
      immunoreactive for transforming growth factor-beta(2) and -beta(3) 1 day after
      injury and 1 day later for transforming growth factor-beta(1). Although
      transforming growth factor-beta(1) and -beta(2), latent transforming growth
      factor-beta(2), transforming growth factor-beta(3), and latent transforming
      growth factor-beta(3) immunostaining was present in the numerous fibroblasts and
      other dermal cells, latent transforming growth factor-beta(1) was only associated
      with the extracellular matrix. In general, immunoreactivity remained high until
      day 7 after wounding and slowly subsided over time. However, by day 21,
      immunostaining had not returned to normal and the original wound was replete with
      immunoreactive fibroblasts and a dense, immunostained extracellular matrix. Thus,
      although the dynamic presence of transforming growth factor-beta isoforms
      exemplifies its positive role in the wound repair process, its persistence
      together with its known potent effects on matrix accumulation, supports its role
      in scar formation.

PMID- 17173644
TI  - Safety and effect of transforming growth factor-beta(2) for treatment of venous
      stasis ulcers.
AB  - Transforming growth factor-beta(2) promotes healing in a variety of animal models
      and exhibits clinical effects thought to be mediated by connective tissue
      formation. Two clinical trials were conducted to evaluate the safety and effect
      of transforming growth factor-beta(2) purified from bovine bone and delivered
      topically to venous stasis ulcers three times per week for up to 6 weeks by means
      of a lyophilized collagen vehicle. The first was an open-label trial comparing
      transforming growth factor-beta(2) purified from bovine bone (0.5 microg/cm(2))
      with a placebo consisting of lyophilized collagen vehicle-without active drug.
      After no safety issues arose in that trial, a prospectively randomized, closed
      label, observer-blinded, three-armed trial was conducted to compare bovine
      transforming growth factor-beta(2) (2.5 microg/cm(2)) with the collagen matrix
      placebo vehicle and with a standard dressing. Standardized elastic compression
      was applied to all test extremities. The rate of reduction of ulcer area as
      measured by planimetry was the primary measure of effect. No serious safety
      related events occurred in either trial. Clinical evaluation suggested that
      improvement in the quality and quantity of granulation tissue appeared to precede
      epithelialization of ulcers treated with bovine transforming growth factor
      beta(2). In both studies, treatment with bovine transforming growth factor
      beta(2) appeared to have a positive effect on the rate of ulcer closure, whereas
      ulcers in the control groups continued to exhibit impaired healing. In the open
      label study, the mean rate of closure of ulcers treated with bovine transforming
      growth factor-beta(2) was significantly greater than that of ulcers treated with
      placebo. There was likewise enhanced reduction in ulcer area in the ulcers
      treated with bovine transforming growth factor-beta(2) in the second trial.
      However, because of a higher variability in patient response and a greater
      placebo effect, the difference was not significant. The placebo was not worse
      than the standard care arm, thereby showing that the vehicle is not injurious to
      healing. The combined results of the two trials suggest that, at doses of 0.5 to
      2.5 microg/cm(2), bovine transforming growth factor-beta(2) is safe as a
      topically applied agent in a collagen matrix vehicle and can have a positive
      effect on closure of venous stasis ulcers. Large multicenter trials appear to be
      indicated to evaluate fully the potential utility of transforming growth factor
      beta(2) in accelerating closure of chronic dermal ulcers.

PMID- 17173645
TI  - Expression of interleukin-6 and tumor necrosis factor in peritoneal mononuclear
      cells after gastrectomy.
AB  - As macrophages are found in peritoneal exudates after abdominal surgery,
      interleukin-6 and tumor necrosis factor-alpha, their messenger RNAs and immune
      specific proteins would also be expected to be found in both peritoneal fluid and
      mononuclear cells under such conditions. The peritoneal fluid and plasma of
      patients who had undergone gastrectomy were investigated on postoperative days 1,
      3, 5, and 7. Evidence of mRNA expression and the intracellular immunocytochemical
      localization of interleukin-6 and tumor necrosis factor-alpha was determined in
      cells isolated from peritoneal fluid, and immune-specific protein levels in the
      peritoneal fluid were measured. Both interleukin-6 and tumor necrosis factor
      alpha proteins were identified immunocytochemically in the cytoplasm of
      peritoneal mononuclear cells, and their mRNAs were detected by the reverse
      transcriptase-polymerase chain reaction. The concentration of interleukin-6 in
      the peritoneal fluid was significantly higher than that in the plasma, and a high
      level of tumor necrosis factor-alpha was found in the peritoneal fluid, despite
      its absence from plasma. Expression and changing levels of interleukin-6 and
      tumor necrosis factor-alpha in human peritoneal fluid after gastrectomy were
      shown, indicating local production of these cytokines, which may play important
      roles in tissue repair.

PMID- 17173646
TI  - Interferons gamma and alpha-2b differentially regulate the expression of
      collagenase and tissue inhibitor of metalloproteinase-1 messenger RNA in human
      hypertrophic and normal dermal fibroblasts.
AB  - We have recently shown that both interferon gamma (gamma) and interferon alpha-2b
      (alpha-2b) markedly depress the expression of messenger RNA for type I
      procollagen and fibronectin in postburn hypertrophic scar and normal dermal
      fibroblasts. In this article we examine the effects of these cytokines on the
      expression of mRNA for collagenase and its natural inhibitor, tissue inhibitor of
      metalloproteinase-1. Twelve different fibroblast cell strains, six from postburn
      hypertrophic scar and six from the normal dermis of the same patients, were
      established in cell culture. The results of a dose response experiment showed
      increases in collagenase mRNA up to 4000 U/ml of interferon-alpha-2b, but maximal
      increases in tissue inhibitor of metalloproteinase mRNA expression and maximal
      decrease in mRNA for type I procollagen at 2000 U/ml. For subsequent experiments
      cells were treated with either interferon-alpha-2b (2000 U/ml) or -gamma (1000
      U/ml) for 96 hours. Quantitative analysis showed increases in tissue inhibitor of
      metalloproteinase-1 and collagenase mRNA (81% and 54%, respectively) in
      interferon-alpha-2b-treated hypertrophic scar fibroblasts. Under the same
      experimental conditions, interferon-alpha-2b had similar effects on normal dermal
      fibroblasts; however, interferon-gamma had a differential effect on the
      expression of mRNA for collagenase and tissue inhibitor of metalloproteinase-1.
      Cells treated with interferon-gamma showed increases in tissue inhibitor of
      metalloproteinase-1 mRNA (78% in hypertrophic scar and 56% in normal dermal
      fibroblasts) but decreases (59% and 42%, respectively) in collagenase mRNA. These
      effects appear to be selective because rehybridization of blots with a
      complementary DNA for tissue inhibitor of metalloproteinase-2 mRNA showed no
      marked alteration in the abundance of this transcript. Significantly greater
      collagenase activity was found in conditioned medium from interferon-alpha-2b
      treated hypertrophic scar cells compared with that from interferon-gamma-treated
      cells. These findings suggest that interferon alpha-2b would have some advantages
      over interferon-gamma for the treatment of dermal fibroproliferative disorders,
      such as postburn hypertrophic scar.

PMID- 17173647
TI  - Hypertrophic scar fibroblasts accelerate collagen gel contraction.
AB  - Excessive contraction of hypertrophic scar and subsequent contracture formation
      are a formidable problem after thermal injury. A comparison between fibroblasts
      from hypertrophic scar and normal skin was made with the use of fibroblast
      populated collagen lattices as a measure of cellular generated contractile
      forces. Hypertrophic scar and normal skin fibroblasts were mixed with soluble
      tendon collagen and Dulbecco's modified Eagle medium supplemented with 10% serum,
      and contraction was measured by serial area measurements. Parallel experiments in
      the presence of transforming growth factor-beta or anti-transforming growth
      factor-beta antibody examined the role of this cytokine on lattice contraction.
      Transforming growth factor-beta activity was measured in an additional set of 10
      biopsy specimens. Hypertrophic scar fibroblasts contract lattices at a
      significantly faster rate than do normal skin fibroblasts. Exogenous transforming
      growth factor-beta increased lattice contraction by normal skin fibroblasts but
      had little effect on hypertrophic scar cell-populated lattices. The addition of
      anti-transforming growth factor-beta antibody decreased lattice contraction by
      both cell types. Transforming growth factor-beta activity was significantly
      increased in the hypertrophic scar biopsy specimens. Excessive scar contraction
      and post-burn scar contracture result from increased contraction forces generated
      by hypertrophic scar cells. This increased contractility appears to be mediated
      by increased endogenous presence of transforming growth factor-beta.

PMID- 17173648
TI  - Differential regulation of collagen gene expression in granulation tissue and non
      repair connective tissues in vitamin C-deficient guinea pigs.
AB  - Poor wound healing during vitamin C deficiency is thought to be due to decreased
      hydroxylation of proline residues in collagen. In non-repair connective tissues
      of guinea pigs, however, procollagen gene expression is not decreased until
      weight loss occurs during the third and fourth weeks of scurvy (phase II) with
      only a moderate decrease in proline hydroxylation. Decreased procollagen gene
      expression is related to the induction of insulin-like growth factor binding
      proteins 1 and 2 that inhibit insulin-like growth factor-I action. We examined
      wound healing and granulation tissue formation during phase I of vitamin C
      deficiency. Synthetic sponges were implanted on day 7 of vitamin C deficiency and
      analyzed at 6 and 10 days after surgery, when there was no weight loss or
      induction of insulin-like growth factor binding proteins. Healing of incisions
      was almost complete at 10 days after surgery in normal controls but not in
      scorbutic animals. The area around the incision and implant exhibited excessive
      angiogenesis and hemorrhaging of vessels in the scorbutic animals at 6 and 10
      days after surgery. At 10 days after surgery, collagen synthesis in the implants
      of scorbutic guinea pigs was 36% lower than control values, with a normal extent
      of proline hydroxylation. Concentrations of messenger RNAs for types I and III
      procollagens were slightly increased by scurvy at 6 days after surgery but were
      decreased by 26% and 40%, respectively, at 10 days. Fibronectin mRNA levels were
      unaffected by scurvy at both time points. Our results suggest that poor wound
      healing in phase I of scurvy may be related to defective interstitial procollagen
      gene expression and defective blood vessel formation, but it does not involve
      inhibition of proline hydroxylation or induction of insulin-like growth factor
      binding proteins. mRNA for insulin-like growth factor-II, transforming growth
      factor-beta(1), and transforming growth factor-beta(2) were significantly
      expressed in implants, but their patterns of expression did not correlate with
      changes in procollagen gene expression.

PMID- 17173649
TI  - Altered collagen metabolism and delayed healing in a novel model of ischemic
      wounds.
AB  - Cellular mechanisms occurring in the healing wound have been well described in
      various animal models. However, the events associated with wound healing seen in
      ischemic skin have not been as thoroughly defined. In this series of experiments,
      we created a novel model of excisional skin wounds under gradient ischemia to
      study the cellular and extracellular events leading to delayed healing. We
      hypothesized that altered collagen metabolism accounts for delayed wound healing
      in ischemic skin. Three pairs of 4 mm punch wounds were made 4 days after
      bipedicle skin flaps were created on the dorsum of rats. Sham-operated control
      animals had the same punch wounds without flap creation. The kinetics of
      excisional wound healing were measured by means of computerized planimetry. In
      addition, wounds were excised with a 6 mm trephine, radiolabelled with ((3)H)
      proline and in vitro collagen synthesis determined as collagenase digestible
      protein along with quantitation of DNA content. Total collagen deposition was
      determined as 4-hydroxy-L-proline by high-performance liquid chromatography, and
      wounds were histologically evaluated. Data was analyzed by means of two-way
      analysis of variance. Although control wounds healed by day 10, flap wounds
      consistently had greater surface area on days 2, 4, 6, 8, and 12 (p < 0.001).
      Relative collagen synthesis (% collagen/noncollagen protein), as measured by an
      in vitro synthesis method, showed no statistically significant differences
      between flap and controls wounds. However, the total collagen content
      (deposition) as measured by 4-hydroxy-l-proline was significantly lower in flap
      wounds compared with controls on days 7 (p < 0.05) and 9 (p < 0.001). In
      addition, a significant increase occurred in DNA content in the flap wounds on
      days 7 (p < 0.05) and 9 (p < 0.001) versus control wounds. These data indicate
      that, in ischemic wounds, significantly less collagen is deposited despite the
      inherent ability of the tissue to synthesize appropriate levels of collagen.
      Because the in vitro collagen synthesis technique only assesses the ability of
      the tissue to synthesize collagen in a well oxygenated environment, one cannot be
      assured that the tissue expresses this potential in vivo. However, these data are
      consistent with the hypothesis that the delay in wound closure is due to an
      alteration in collagen metabolism which results in a net decrease in collagen
      accumulation. Because of the observed increase in DNA within the ischemic wounds,
      we suggest that there is prolonged inflammation in these wounds which may enhance
      collagen degradation through the release of proteases. In addition, there may be
      an inability of the tissue to maintain appropriate levels of collagen in this
      inflammatory wound environment.

PMID- 17173650
TI  - Capillary morphogenesis during healing of full-thickness skin grafts: an
      ultrastructural study.
AB  - Biologic mechanisms by which skin grafts become revascularized after
      transplantation are poorly understood. To investigate graft revascularization, we
      examined the pattern of capillary growth in full-thickness skin grafts at serial
      time points. Full-thickness skin (2 x 2 cm) was excised to muscle fascia from the
      bilateral hind limbs of adult male Lewis rats. The graft/wound base boundary was
      identified by placement of a polypropylene mesh on the wound beneath the graft.
      Excised skin was replaced in its original orientation and secured with silk
      sutures tied over a gauze bolster dressing. After 3, 5, 7, and 10 days, animals
      were killed, and their aortas were cannulated and infused with an acrylic polymer
      to generate vascular casts. Grafts were excised, tissues were digested, and casts
      were examined with the use of scanning electron microscopy. Transmission electron
      microscopy was performed on tissues infused with the acrylic polymer that were
      not digested. At day 3, an immature lobular pattern was observed extending from
      the neovascular plexi on the graft side of the polypropylene mesh. At day 5,
      defined vessels with lobular ends occurred with high frequency. At day 7, the
      number of observed lobular structures was greatly reduced, and high frequencies
      of depressions in acrylic casts suggested protrusion of endothelial cell nuclei.
      By day 10, lobular structures were rare, well-defined microvascular plexi were
      contiguous with larger vessels, and depressions from endothelial cell nuclei
      appeared more shallow and less frequent. These findings suggest that (1) an
      immature lobular pattern representing either capillary outgrowth or
      extracapillary leakage occurs at day 3; (2) these immature lobules decrease, and
      more discrete capillaries increase by day 5; (3) vascular integrity is
      reestablished by day 7; (4) vascular plexi has regained full continuity, and
      there are suggestions that endothelial cell proliferation has subsided by day 10.

PMID- 17173651
TI  - Pancreatic islet transplantation prevents the impaired healing of intestinal
      anastomoses in Lewis rats with streptozotocin-induced diabetes.
AB  - Pancreatic islet transplantation may prevent secondary complications of diabetes
      mellitus, but its potential benefits on early complications have been
      incompletely examined. The objective of this study was to investigate whether
      preoperative islet transplantation would normalize impaired healing of intestinal
      anastomoses in diabetic rats. Male Lewis rats were divided into a control group
      (I), an uncontrolled diabetic group (II), and a transplant group (III). Nine days
      before surgery, groups II and III were rendered diabetic by injection of
      streptozotocin. Two days before surgery, group III received an intrahepatic
      isogenic two-donor islet graft, whereas groups I and II underwent sham
      transplantation. On day 0, all animals underwent resection and anastomosis of
      both ileum and colon. Half of the animals in each group were killed on day 3 and
      the other half were killed on day 7. Blood glucose levels in group II rats
      remained over 20 mmol/L throughout the experiment, whereas in group III rats they
      were normalized within 24 hours after transplantation. At death, group II rats,
      but not groups I and III rats, showed a high incidence of anastomotic abscesses.
      Uncontrolled diabetes lowered anastomotic strength, and transplantation prevented
      this reduction. For instance, anastomotic bursting pressure in the ileum on day 3
      was 11.9 +/- 4.8 kPa in group I rats, 3.3 +/- 3.0 kPa in group II rats, and 11.1
      +/- 4.3 kPa in group III rats. Rupture on day 3 always occurred within the
      anastomosis, whereas on day 7 intra-anastomotic ruptures were only observed in
      group II rats. No differences between the groups were found for either
      anastomotic hydroxyproline concentration or content. However, the acid solubility
      of anastomotic collagen was significantly higher in group II rats than in groups
      I and III rats. Thus, uncontrolled diabetes lowers anastomotic strength without
      affecting anastomotic collagen content. Defective repair is prevented by
      pancreatic islet transplantation before surgery.

PMID- 17173652
TI  - The role of transforming growth factor-beta in the conversion from "scarless"
      healing to healing with scar formation.
AB  - The objective of this study was to elucidate mediators responsible for conversion
      of "scarless" wound healing seen in wounded, day 14 fetal mouse limbs to healing
      with scar formation seen in wounded, day 18 fetal mouse limbs. Wounded, day 14
      limbs were grown in a serum-free organ culture system in which either phosphate
      buffered saline solution or human recombinant transforming growth factor beta-1
      (1 microg/ml) was added daily. Wounded, day 18 limbs were also maintained in the
      same organ culture system with either phosphate-buffered saline solution or
      neutralizing antibody to transforming growth factor-beta (1 microg/ml) treatment.
      Limb cross sections were examined qualitatively with Masson's Trichrome stain and
      quantitatively by spectrophotometric analysis of Sirius Red and Fast Green dyes
      which bind to collagen and noncollagenous protein, respectively. Both qualitative
      and quantitative analyses showed the following: there was greater collagen
      deposition in day 18 versus day 14 limbs by 7 days after wounding, scar formation
      in day 18 limbs was attenuated by the addition of anti-transforming growth factor
      beta, and there was the addition of transforming growth factor-beta-augmented
      collagenous scar formation in wounded regions of day 14 limbs. These results
      strongly suggest that transforming growth factor-beta present in the local wound
      environment is, at least in part, responsible for the conversion of "scarless"
      healing occurring in wounded, day 14 limbs to scar formation present in wounded,
      day 18 limbs.

PMID- 17173653
TI  - Wound healing research in China.

PMID- 17173654
TI  - Errors in ABO labeling of deceased donor kidneys: case reports and approach to
      ensuring patient safety.
AB  - Patient safety in transplantation depends on accurate testing, transcription and
      transmission of the ABO types of the donor and recipient. Similar to 'near-miss'
      transfusion labeling errors, three cases of mislabeled ABO types on deceased
      donor kidney containers were recognized through a pretransplant verification
      process. Six steps to confirming the organ and ABO identification were developed
      to ensure safety of the patient and prevent liability for the transplant team and
      facility. In each case, rapid recognition and documentation of the error source,
      on site confirmation of the ABO type of the accompanying blood specimen, and full
      disclosure to the patient and family permitted safe transplantation and avoided
      the need to pursue a more conservative course that would have required discarding
      the organs. We advocate following these measures in determining whether to
      persevere with transplantation of a mislabeled organ.

PMID- 17173655
TI  - A "weight-listing" paradox for candidates of renal transplantation?
AB  - Research suggests that end-stage renal disease patients with elevated body mass
      index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI
      patients represent the highest risk cohorts for kidney transplant recipients. The
      important question remains concerning how to manage transplant candidates given
      the potentially incommensurate impact of BMI by treatment modality. We conducted
      a retrospective analysis of waitlisted and transplanted patients in the United
      States from 1990 to 2003. We constructed Cox models to evaluate the effect of BMI
      on mortality of waitlisted candidates and identified risk factors for rapid
      weight change. We then assessed the impact of weight change during waitlisting on
      transplant outcomes. Decline in BMI on the waiting list was not protective for
      posttransplant mortality or graft loss across BMI strata. Substantial weight loss
      pretransplantation was associated with rapid gain posttransplantation. The
      highest risk for death was among listed patients with low BMI (13-20 kg/m(2),
      adjusted hazard ratio = 1.47, p < 0.01). Approximately one-third of candidates
      had a change in BMI category prior to transplantation. While observed declines in
      BMI may be volitional or markers of disease processes, there is no evidence that
      candidates have improved transplant outcomes attributable to weight loss.
      Prospective trials are needed to evaluate the efficacy of weight loss protocols
      for candidates of kidney transplantation.

PMID- 17173656
TI  - Mouse strain and injection site are crucial for detecting linked suppression in
      transplant recipients by trans-vivo DTH assay.
AB  - Chemokine-driven accumulation of lymphocytes, mononuclear and polymorphonuclear
      proinflammatory cells in antigenic tissue sites is a key feature of several types
      of T-cell-dependent autoimmunity and transplant rejection pathology. It is now
      clear that the immune system expends considerable energy to control this process,
      exemplified by the sequential layers of regulatory cell input, both innate and
      adaptive, designed to prevent a classical Type IV or 'delayed-type'
      hypersensitivity (DTH) reaction from occurring in the visual field of the eye.
      Yet, despite an abundance of in vitro assays currently available to the human T
      cell immunologist, none of them adequately models the human DTH response and its
      various control features. The theme of this article is that it is relatively easy
      to model the effector side of the human DTH response with xenogeneic adoptive
      transfer models. However, we show that in order to detect inhibition of a recall
      DTH in response to colocalized donor antigen (linked suppression)--a
      characteristic feature of peripheral tolerance to an organ transplant--both the
      challenge site and the immunocompetence of the mouse adoptive host are critical
      factors limiting the sensitivity of the trans-vivo DTH test.

PMID- 17173657
TI  - Living-related versus deceased donor pediatric liver transplantation: a
      multivariate analysis of technical and immunological complications in 235
      recipients.
AB  - Timely access to a living donor (LD) reduced pretransplant mortality in pediatric
      liver transplantation (LT). We hypothesized that this strategy may provide better
      posttransplant outcome. Between July 1993 and April 2002, 235 children received a
      primary LT from a LD (n = 100) or a deceased donor (DD) (n = 135). Demographic,
      surgical and immunological variables were compared, and respective impact on
      posttransplant complications was studied using a multivariate analysis. Five-year
      patient survival rates were 92% and 85% for groups LD and DD, respectively (p =
      0.181), the corresponding graft survival rates being 89% and 77% (p = 0.033). At
      multivariate analysis: (1) type of donor (DD) was correlated with higher rate of
      artery thrombosis (p < 0.012); (2) biliary complication rate at 5 years was 29%
      and 23% for groups LD and DD, respectively (p = 0.451); (3) lower acute rejection
      incidence could be correlated with type of donor (DD) (p = 0.001), and
      immunosuppressive therapy (tacrolimus) (p < 0.001). We conclude that (1)
      according to the multivariate analysis, LT with LD provided similar patient and
      graft outcome, when compared to DD; (2) a higher rate of artery thrombosis and a
      lower rate of rejection were observed in group DD; (3) this study confirms the
      efficacy of tacrolimus for immunoprophylaxis, whatever the type of organ donor
      is.

PMID- 17173658
TI  - Heightened expression of the cytotoxicity receptor NKG2D correlates with acute
      and chronic nephropathy after kidney transplantation.
AB  - The activating cytotoxicity receptor NKG2D binds to stress-regulated molecules
      encoded by the major histocompatibility complex class I chain-related (MIC) and
      UL-16-binding protein (ULBP)/retinoic acid early transcript (RAET) gene family.
      To assess whether acute allograft rejection leads to an induction of these
      inducible ligands and their receptor NKG2D, we examined the mRNA profiles in
      kidney transplant biopsies. Expression levels were correlated with the incidence
      of acute rejection (aRx) episodes and chronic allograft nephropathy (CAN) proven
      by histology. Whereas MICA, ULBP1/3 and RAET1-E did not display heightened gene
      expression, elevated levels of NKG2D mRNA could be associated with aRx (p <
      0.001). Immunohistology of kidney biopsies diagnosed with aRx revealed NKG2D+
      cells in tubulointerstitial areas positive for CD8+ cells. Most importantly,
      elevated levels of NKG2D mRNA were associated with restricted long-term graft
      function assessed by the glomerular filtration rate at 6, 12 and 18 months
      posttransplantation. Induced NKG2D mRNA expression was still observable in
      biopsies diagnosed with CAN (p < 0.001), demonstrating a higher sensitivity and
      specificity compared to CD3, granzyme B and granulysin mRNA measurement.
      Significant elevated levels of NKG2D mRNA could be further detected in urine
      sediment prior to aRx, suggesting this receptor as a new candidate marker for the
      diagnosis of acute and chronic allograft rejection.

PMID- 17173659
TI  - Increasing live donor kidney transplantation: a randomized controlled trial of a
      home-based educational intervention.
AB  - With the shortage of deceased donor kidneys and the superior clinical outcomes
      possible with live donor kidney transplantation (LDKT), more patients should
      seriously consider LDKT. However, little is known about how best to educate
      patients and their family members about LDKT. We evaluated the effectiveness of a
      home-based (HB) educational program in increasing LDKT. Patients were randomized
      to clinic-based (CB) education alone (CB, n = 69) or CB plus HB education (CB+HB,
      n = 63). Compared to CB, more patients in the CB+HB group had living donor
      inquiries (63.8% vs. 82.5%, p = 0.019) and evaluations (34.8% vs. 60.3%, p =
      0.005) and LDKTs (30.4% vs. 52.4%, p = 0.013). Assignment to the CB+HB group,
      White race, more LDKT knowledge, higher willingness to discuss LDKT with others,
      and fewer LDKT concerns were predictors of having LDKT (p-values < 0.05). Both
      groups demonstrated an increase in LDKT knowledge after the CB education, but
      CB+HB led to an additional increase in LDKT knowledge (p < 0.0001) and in
      willingness to discuss LDKT with others (p < 0.0001), and a decrease in LDKT
      concerns (p < 0.0001). Results indicate that an HB outreach program is more
      effective in increasing LDKT rates than CB education alone.

PMID- 17173660
TI  - Simple measures to monitor beta-cell mass and assess islet graft dysfunction.
AB  - The aim of this study was to develop a simple test for the assessment of islet
      graft dysfunction based on measures involving fasting C-peptide. Calculations
      were made to account for the dependence of C-peptide secretion on glucose
      concentration (C-peptide/glucose ratio [CP/G]) and adjusted for renal function by
      calculating the C-peptide/glucose-creatinine ratio (CP/GCr). Values from 22
      recipients were analyzed at different times post-last islet infusion. Receiver
      operating characteristic curves were used to determine which of these measures
      best predicts high 90-minute glucose (90 min-Glc; >10 mmol/L) after a Mixed Meal
      Tolerance Test (MMTT). In this initial analysis, CP/G was found to be superior
      predicting high 90 min-Glc with a larger area under the ROC curve than C-peptide
      (p = 0.01) and CP/GCr (p = 0.06). We then correlated C-peptide and CP/G with
      islet equivalents--IEQ/kg infused, 90 min-Glc after MMTT and clinical outcome
      (beta-score). C-peptide and CP/G in the first 3 months post-last islet infusion
      correlated with IEQ/kg infused. CP/G correlated with 90 min-Glc and beta-score. C
      peptide and CP/G are good indicators of islet mass transplanted. CP/G is more
      indicative of graft dysfunction and clinical outcome than C-peptide alone. The
      ease of calculation and the good correlation with other tests makes this ratio a
      practical tool when monitoring and managing islet transplant recipients.

PMID- 17173661
TI  - Histological benefit of retreatment by pegylated interferon alfa-2b and ribavirin
      in patients with recurrent hepatitis C virus infection posttransplantation.
AB  - We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin
      in patients who did not respond to previous posttransplant recurrent HCV
      treatment with IFN/ribavirin combination. Twenty-seven patients were
      consecutively included in this study and retreated with pegylated interferon alfa
      2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for
      genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21
      untreated patients enrolled during the same period. Primary endpoint was the SVR
      and secondary endpoint was histological evaluation 24 weeks after ending therapy.
      Twenty-seven patients started therapy but 2 (7%) stopped because of side effects.
      On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as
      immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02)
      were significantly associated with viral clearance. In 46 patients in whom paired
      graft biopsies were available, fibrosis score was improved in 76% of treated
      patients versus 5% in untreated patients. Among treated patients, improvement of
      fibrosis was not correlated to SVR. Our data show that 30% of patients who have
      failed prior posttransplantation treatment achieved an SVR when retreated with
      pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score
      was improved in 65% of treated patients despite failure of HCV eradication.

PMID- 17173662
TI  - Fasting and nutrient-stimulated plasma peptide-YY levels are elevated in critical
      illness and associated with feed intolerance: an observational, controlled study.
AB  - INTRODUCTION: Delayed gastric emptying and feed intolerance occur frequently in
      the critically ill. In these patients, gastric motor responses to nutrients are
      disturbed. Peptide YY (PYY) slows gastric emptying. The aim of this study was to
      determine fasting and nutrient-stimulated plasma PYY concentrations and their
      relationship to cholecystokinin (CCK) in critically ill patients. METHODS:
      Studies were performed in 19 unselected mechanically ventilated critically ill
      patients (12 males; 48 +/- 7 years old) in a randomised, single-blind fashion.
      Subjects received a 60-minute duodenal infusion of Ensure at either 1 or 2
      kcal/minute. Blood samples were collected at baseline and at 20, 40, 60, and 180
      minutes following commencement of the nutrient infusion for the measurement of
      plasma PYY and CCK concentrations (using radioimmunoassay). Patient data were
      compared to 24 healthy subjects (17 males; 43 +/- 2 years old). RESULTS: Fasting
      PYY concentration was higher in patients (P < 0.05), particularly in those with
      feed intolerance (P < 0.05). Plasma PYY concentrations were higher in patients
      during nutrient infusion (area under the curve [AUC] at 1 kcal/minute: 2,265 +/-
      718 versus 1,125 +/- 138 pmol/l.min, P < 0.05; at 2 kcal/minute: 2,276 +/- 303
      versus 1,378 +/- 210 pmol/l.min, P = 0.01) compared to healthy subjects. The
      magnitude of PYY elevation was greater in patients during the 1 kcal/minute
      infusion (AUC: 441 +/- 153 versus 186 +/- 58 pmol/l.min, P < 0.05), but not the 2
      kcal/minute infusion. Fasting and nutrient-stimulated plasma CCK concentrations
      were higher in patients (P < 0.05). There was a relationship between plasma PYY
      and CCK concentrations during fasting (r = 0.52, P < 0.05) and nutrient infusion
      (r = 0.98, P < 0.0001). CONCLUSION: In critical illness, both fasting and
      nutrient-stimulated plasma PYY concentrations are elevated, particularly in
      patients with feed intolerance, in conjunction with increased CCK concentrations.

PMID- 17173664
TI  - The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and
      reduces overactivity and impulsiveness in an animal model of Attention
      Deficit/Hyperactivity Disorder (ADHD).
AB  - BACKGROUND: ADHD is currently defined as a cognitive/behavioral developmental
      disorder where all clinical criteria are behavioral. Overactivity, impulsiveness,
      and inattentiveness are presently regarded as the main clinical symptoms. There
      is no biological marker, but there is considerable evidence to suggest that ADHD
      behavior is associated with poor dopaminergic and noradrenergic modulation of
      neuronal circuits that involve the frontal lobes. The best validated animal model
      of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity,
      impulsiveness, and deficient sustained attention. While dopamine release is
      decreased in SHR prefrontal cortex, norepinephrine concentrations are elevated.
      The noradrenergic system appears to be hyperactive as a result of impaired alpha
      2A adrenoceptor regulation. Thus, the present study tested behavioral effects of
      the centrally acting alpha-2A adrenoceptor agonist guanfacine on SHR behavior.
      METHODS: The present study tested behavioral effects of guanfacine at doses of
      0.075, 0.15, 0.30 and 0.60 mg base/kg i.p. in both male SHRs and their controls,
      the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual
      discrimination task measuring overactivity, impulsiveness and inattentiveness.
      RESULTS: The striking impulsiveness, overactivity, and reduced sustained
      attention during baseline conditions in the SHR improved by treatment with
      guanfacine. The most pronounced improvement in SHR behavior was seen following
      the two highest doses (0.3 and 0.6 mg/kg) of guanfacine when SHR behaviors
      virtually normalized. The positive effects of the drug were most marked towards
      the end of the session. CONCLUSION: The results indicate that guanfacine improved
      poor noradrenergic modulation of neuronal circuits that involve the frontal lobes
      in an animal model of ADHD. The present results support the beneficial effects of
      guanfacine on ADHD behavior reported clinically and experimentally in primate
      models of frontal function. It is likely that guanfacine improved prefrontal
      functions in the SHR. It cannot be concluded, however, that the effects of the
      drug are mediated solely by norepinephrine.

PMID- 17173663
TI  - Anthroposophic therapy for chronic depression: a four-year prospective cohort
      study.
AB  - BACKGROUND: Depressive disorders are common, cause considerable disability, and
      do not always respond to standard therapy (psychotherapy, antidepressants).
      Anthroposophic treatment for depression differs from ordinary treatment in the
      use of artistic and physical therapies and special medication. We studied
      clinical outcomes of anthroposophic therapy for depression. METHODS: 97
      outpatients from 42 medical practices in Germany participated in a prospective
      cohort study. Patients were aged 20-69 years and were referred to anthroposophic
      therapies (art, eurythmy movement exercises, or rhythmical massage) or started
      physician-provided anthroposophic therapy (counselling, medication) for
      depression: depressed mood, at least two of six further depressive symptoms,
      minimum duration six months, Center for Epidemiological Studies Depression Scale,
      German version (CES-D, range 0-60 points) of at least 24 points. Outcomes were
      CES-D (primary outcome) and SF-36 after 3, 6, 12, 18, 24, and 48 months. Data
      were collected from July 1998 to March 2005. RESULTS: Median number of
      art/eurythmy/massage sessions was 14 (interquartile range 12-22), median therapy
      duration was 137 (91-212) days. All outcomes improved significantly between
      baseline and all subsequent follow-ups. Improvements from baseline to 12 months
      were: CES-D from mean (standard deviation) 34.77 (8.21) to 19.55 (13.12) (p <
      0.001), SF-36 Mental Component Summary from 26.11 (7.98) to 39.15 (12.08) (p <
      0.001), and SF-36 Physical Component Summary from 43.78 (9.46) to 48.79 (9.00) (p
      < 0.001). All these improvements were maintained until last follow-up. At 12
      month follow-up and later, 52%-56% of evaluable patients (35%-42% of all
      patients) were improved by at least 50% of baseline CES-D scores. CES-D improved
      similarly in patients not using antidepressants or psychotherapy during the first
      six study months (55% of patients). CONCLUSION: In outpatients with chronic
      depression, anthroposophic therapies were followed by long-term clinical
      improvement. Although the pre-post design of the present study does not allow for
      conclusions about comparative effectiveness, study findings suggest that the
      anthroposophic approach, with its recourse to non-verbal and artistic exercising
      therapies can be useful for patients motivated for such therapies.

PMID- 17173665
TI  - A bibliometric analysis in the fields of preventive medicine, occupational and
      environmental medicine, epidemiology, and public health.
AB  - BACKGROUND: Research in the fields of Preventive Medicine,
      Occupational/Environmental Medicine, Epidemiology and Public Health play an
      important role in the advancement of knowledge. In order to map the research
      production around the world we performed a bibliometric analysis in the above
      fields. METHODS: All articles published by different world regions in the above
      mentioned scientific fields and cited in the Journal Citation Reports (JCR)
      database of the Institute for Scientific Information (ISI) during the period 1995
      and 2003, were evaluated. The research production of different world regions was
      adjusted for: a) the gross domestic product in 1995 US dollars, and b) the
      population size of each region. RESULTS: A total of 48,861 articles were
      retrieved and categorized. The USA led the research production in all three
      subcategories. The percentage of articles published by USA researchers was 43%,
      44% and 61% in the Preventive Medicine, Epidemiology, and Public Health
      subcategories, respectively. Canada and Western Europe shared the second position
      in the first two subcategories, while Oceania researchers ranked second in the
      field of Public Health. CONCLUSION: USA researchers maintain a leadership
      position in the production of scientific articles in the fields of Preventive
      Medicine, Occupational/Environmental Medicine and Epidemiology, at a level
      similar to other scientific disciplines, while USA contribution to science in the
      field of Public Health is by all means outstanding. Less developed regions would
      need to support their researchers in the above fields in order to improve
      scientific production and advancement of knowledge in their countries.

PMID- 17173666
TI  - Lack of association between COMT gene and deficit/nondeficit schizophrenia.
AB  - BACKGROUND: The dopamine dysregulation hypothesis of schizophrenia posits that
      positive, negative and cognitive symptoms correlate with cortical/subcortical
      imbalances in dopaminergic transmission. A functional polymorphism (Val158Met) in
      the catechol-O-methyltransferase (COMT) gene is implicated in the pathophysiology
      of schizophrenia by its effect on prefrontal dopamine transmission, and its
      unique impact on prefrontal cognitive and behavioral phenotypes. Cognitive
      impairments and negative symptoms in schizophrenia have been hypothesized to be
      associated with hypodopaminergic states. Schizophrenia patients with the deficit
      syndrome are characterized by primary enduring negative symptoms, impairment on
      neurocognitive tasks sensitive to frontal and parietal cortical functioning, and
      poorer functional outcome compared to non-deficit patients. METHODS: Eighty-six
      schizophrenia cases that met DSM-IV criteria for schizophrenia were recruited.
      Additional categorization into deficit and nondeficit syndrome was performed
      using the Schedule for the Deficit Syndrome (SDS). A healthy comparison group (n
      = 50) matched to cases on age and ethnicity was recruited. Allele and genotype
      frequencies of the Val158Met polymorphism were compared among healthy controls,
      and schizophrenia cases with the deficit (n = 21), and nondeficit syndrome (n =
      65). RESULTS: There was a significant difference in Val/Val genotype frequencies
      between schizophrenia cases (combined deficit/nondeficit) and healthy controls (p
      = 0.004). No significant differences in allele or genotype frequencies were
      observed between deficit and nondeficit cases. CONCLUSION: Results from this
      preliminary analysis failed to show an effect of COMT gene on deficit
      schizophrenia.

PMID- 17173668
TI  - Municipal mortality due to thyroid cancer in Spain.
AB  - BACKGROUND: Thyroid cancer is a tumor with a low but growing incidence in Spain.
      This study sought to depict its spatial municipal mortality pattern, using the
      classic model proposed by Besag, York and Mollie. METHODS: It was possible to
      compile and ascertain the posterior distribution of relative risk on the basis of
      a single Bayesian spatial model covering all of Spain's 8077 municipal areas.
      Maps were plotted depicting standardized mortality ratios, smoothed relative risk
      (RR) estimates, and the posterior probability that RR > 1. RESULTS: From 1989 to
      1998 a total of 2,538 thyroid cancer deaths were registered in 1,041
      municipalities. The highest relative risks were mostly situated in the Canary
      Islands, the province of Lugo, the east of La Coruna (Corunna) and western areas
      of Asturias and Orense. CONCLUSION: The observed mortality pattern coincides with
      areas in Spain where goiter has been declared endemic. The higher frequency in
      these same areas of undifferentiated, more aggressive carcinomas could be
      reflected in the mortality figures. Other unknown genetic or environmental
      factors could also play a role in the etiology of this tumor.

PMID- 17173667
TI  - The level of BMP4 signaling is critical for the regulation of distinct T-box gene
      expression domains and growth along the dorso-ventral axis of the optic cup.
AB  - BACKGROUND: Polarised gene expression is thought to lead to the graded
      distribution of signaling molecules providing a patterning mechanism across the
      embryonic eye. Bone morphogenetic protein 4 (Bmp4) is expressed in the dorsal
      optic vesicle as it transforms into the optic cup. Bmp4 deletions in human and
      mouse result in failure of eye development, but little attempt has been made to
      investigate mammalian targets of BMP4 signaling. In chick, retroviral gene
      overexpression studies indicate that Bmp4 activates the dorsally expressed Tbx5
      gene, which represses ventrally expressed cVax. It is not known whether the Tbx5
      related genes, Tbx2 and Tbx3, are BMP4 targets in the mammalian retina and
      whether BMP4 acts at a distance from its site of expression. Although it is
      established that Drosophila Dpp (homologue of vertebrate Bmp4) acts as a
      morphogen, there is little evidence that BMP4 gradients are interpreted to create
      domains of BMP4 target gene expression in the mouse. RESULTS: Our data show that
      the level of BMP4 signaling is critical for the regulation of distinct Tbx2,
      Tbx3, Tbx5 and Vax2 gene expression domains along the dorso-ventral axis of the
      mouse optic cup. BMP4 signaling gradients were manipulated in whole mouse embryo
      cultures during optic cup development, by implantation of beads soaked in BMP4,
      or the BMP antagonist Noggin, to provide a local signaling source. Tbx2, Tbx3 and
      Tbx5, showed a differential response to alterations in the level of BMP4 along
      the entire dorso-ventral axis of the optic cup, suggesting that BMP4 acts across
      a distance. Increased levels of BMP4 caused expansion of Tbx2 and Tbx3, but not
      Tbx5, into the ventral retina and repression of the ventral marker Vax2.
      Conversely, Noggin abolished Tbx5 expression but only shifted Tbx2 expression
      dorsally. Increased levels of BMP4 signaling caused decreased proliferation,
      reduced retinal volume and altered the shape of the optic cup. CONCLUSION: Our
      findings suggest the existence of a dorsal-high, ventral-low BMP4 signaling
      gradient across which distinct domains of Tbx2, Tbx3, Tbx5 and Vax2 transcription
      factor gene expression are set up. Furthermore we show that the correct level of
      BMP4 signaling is critical for normal growth of the mammalian embryonic eye.

PMID- 17173669
TI  - Bringing metabolic networks to life: convenience rate law and thermodynamic
      constraints.
AB  - BACKGROUND: Translating a known metabolic network into a dynamic model requires
      rate laws for all chemical reactions. The mathematical expressions depend on the
      underlying enzymatic mechanism; they can become quite involved and may contain a
      large number of parameters. Rate laws and enzyme parameters are still unknown for
      most enzymes. RESULTS: We introduce a simple and general rate law called
      "convenience kinetics". It can be derived from a simple random-order enzyme
      mechanism. Thermodynamic laws can impose dependencies on the kinetic parameters.
      Hence, to facilitate model fitting and parameter optimisation for large networks,
      we introduce thermodynamically independent system parameters: their values can be
      varied independently, without violating thermodynamical constraints. We achieve
      this by expressing the equilibrium constants either by Gibbs free energies of
      formation or by a set of independent equilibrium constants. The remaining system
      parameters are mean turnover rates, generalised Michaelis-Menten constants, and
      constants for inhibition and activation. All parameters correspond to molecular
      energies, for instance, binding energies between reactants and enzyme.
      CONCLUSION: Convenience kinetics can be used to translate a biochemical network-
      manually or automatically--into a dynamical model with plausible biological
      properties. It implements enzyme saturation and regulation by activators and
      inhibitors, covers all possible reaction stoichiometries, and can be specified by
      a small number of parameters. Its mathematical form makes it especially suitable
      for parameter estimation and optimisation. Parameter estimates can be easily
      computed from a least-squares fit to Michaelis-Menten values, turnover rates,
      equilibrium constants, and other quantities that are routinely measured in enzyme
      assays and stored in kinetic databases.

PMID- 17173670
TI  - Bringing metabolic networks to life: integration of kinetic, metabolic, and
      proteomic data.
AB  - BACKGROUND: Translating a known metabolic network into a dynamic model requires
      reasonable guesses of all enzyme parameters. In Bayesian parameter estimation,
      model parameters are described by a posterior probability distribution, which
      scores the potential parameter sets, showing how well each of them agrees with
      the data and with the prior assumptions made. RESULTS: We compute posterior
      distributions of kinetic parameters within a Bayesian framework, based on
      integration of kinetic, thermodynamic, metabolic, and proteomic data. The
      structure of the metabolic system (i.e., stoichiometries and enzyme regulation)
      needs to be known, and the reactions are modelled by convenience kinetics with
      thermodynamically independent parameters. The parameter posterior is computed in
      two separate steps: a first posterior summarises the available data on enzyme
      kinetic parameters; an improved second posterior is obtained by integrating
      metabolic fluxes, concentrations, and enzyme concentrations for one or more
      steady states. The data can be heterogeneous, incomplete, and uncertain, and the
      posterior is approximated by a multivariate log-normal distribution. We apply the
      method to a model of the threonine synthesis pathway: the integration of
      metabolic data has little effect on the marginal posterior distributions of
      individual model parameters. Nevertheless, it leads to strong correlations
      between the parameters in the joint posterior distribution, which greatly improve
      the model predictions by the following Monte-Carlo simulations. CONCLUSION: We
      present a standardised method to translate metabolic networks into dynamic
      models. To determine the model parameters, evidence from various experimental
      data is combined and weighted using Bayesian parameter estimation. The resulting
      posterior parameter distribution describes a statistical ensemble of parameter
      sets; the parameter variances and correlations can account for missing knowledge,
      measurement uncertainties, or biological variability. The posterior distribution
      can be used to sample model instances and to obtain probabilistic statements
      about the model's dynamic behaviour.

PMID- 17173671
TI  - A computational analysis of the three isoforms of glutamate dehydrogenase reveals
      structural features of the isoform EC 1.4.1.4 supporting a key role in ammonium
      assimilation by plants.
AB  - BACKGROUND: There are three isoforms of glutamate dehydrogenase. The isoform EC
      1.4.1.4 (GDH4) catalyses glutamate synthesis from 2-oxoglutarate and ammonium,
      using NAD(P)H. Ammonium assimilation is critical for plant growth. Although GDH4
      from animals and prokaryotes are well characterized, there are few data
      concerning plant GDH4, even from those whose genomes are well annotated. RESULTS:
      A large set of the three GDH isoforms was built resulting in 116 non-redundant
      full polypeptide sequences. A computational analysis was made to gain more
      information concerning the structure-function relationship of GDH4 from plants
      (Eukaryota, Viridiplantae). The tested plant GDH4 sequences were the two ones
      known to date, those of Chlorella sorokiniana. This analysis revealed several
      structural features specific of plant GDH4: (i) the lack of a structure called
      "antenna"; (ii) the NAD(P)-binding motif GAGNVA; and (iii) a second putative
      coenzyme-binding motif GVLTGKG together with four residues involved in the
      binding of the reduced form of NADP. CONCLUSION: A number of structural features
      specific of plant GDH4 have been found. The results reinforce the probable key
      role of GDH4 in ammonium assimilation by plants. REVIEWERS: This article was
      reviewed by Tina Bakolitsa (nominated by Eugene Koonin), Martin Jambon (nominated
      by Laura Landweber), Sandor Pangor and Franck Eisenhaber.

PMID- 17173672
TI  - A community-based health education programme for bio-environmental control of
      malaria through folk theatre (Kalajatha) in rural India.
AB  - BACKGROUND: Health education is an important component in disease control
      programme. Kalajatha is a popular, traditional art form of folk theatre depicting
      various life processes of a local socio-cultural setting. It is an effective
      medium of mass communication in the Indian sub-continent especially in rural
      areas. Using this medium, an operational feasibility health education programme
      was carried out for malaria control. METHODS: In December 2001, the Kalajatha
      events were performed in the evening hours for two weeks in a malaria-affected
      district in Karnataka State, south India. Thirty local artists including ten
      governmental and non-governmental organizations actively participated. Impact of
      this programme was assessed after two months on exposed vs. non-exposed
      respondents. RESULTS: The exposed respondents had significant increase in
      knowledge and change in attitude about malaria and its control strategies,
      especially on bio-environmental measures (p < 0.001). They could easily associate
      clean water with anopheline breeding and the role of larvivorous fish in malaria
      control. In 2002, the local community actively co-operated and participated in
      releasing larvivorous fish, which subsequently resulted in a noteworthy reduction
      of malaria cases. Immediate behavioural changes, especially maintenance of
      general sanitation and hygiene did not improve as much as expected. CONCLUSION:
      This study was carried out under the primary health care system involving the
      local community and various potential partners. Kalajatha conveyed the important
      messages on malaria control and prevention to the rural community. Similar
      methods of communication in the health education programme should be intensified
      with suitable modifications to reach all sectors, if malaria needs to be
      controlled.

PMID- 17173673
TI  - The biological sense of cancer: a hypothesis.
AB  - BACKGROUND: Most theories about cancer proposed during the last century share a
      common denominator: cancer is believed to be a biological nonsense for the
      organism in which it originates, since cancer cells are believed to be ones
      evading the rules that control normal cell proliferation and differentiation. In
      this essay, we have challenged this interpretation on the basis that, throughout
      the animal kingdom, cancer seems to arise only in injured organs and tissues that
      display lost or diminished regenerative ability. HYPOTHESIS: According to our
      hypothesis, a tumor cell would be the only one able to respond to the demand to
      proliferate in the organ of origin. It would be surrounded by "normal" aged cells
      that cannot respond to that signal. According to this interpretation, cancer
      would have a profound biological sense: it would be the ultimate way to attempt
      to restore organ functions and structures that have been lost or altered by aging
      or noxious environmental agents. In this way, the features commonly associated
      with tumor cells could be reinterpreted as progressively acquired adaptations for
      responding to a permanent regenerative signal in the context of tissue injury.
      Analogously, several embryo developmental stages could be dependent on cellular
      damage and death, which together disrupt the field topography. However, unlike
      normal structures, cancer would have no physiological value, because the usually
      poor or non-functional nature of its cells would make their reparative task
      unattainable. CONCLUSION: The hypothesis advanced in this essay might have
      significant practical implications. All conventional therapies against cancer
      attempt to kill all cancer cells. However, according to our hypothesis, the
      problem might not be solved even if all the tumor cells were eradicated. In
      effect, if the organ failure remained, new tumor cells would emerge and the tumor
      would reinitiate its progressive growth in response to the permanent regenerative
      signal of the non-restored organ. Therefore, efficient anti-cancer therapy should
      combine an attack against the tumor cells themselves with the correction of the
      organ failure, which, according to this hypothesis, is fundamental to the origin
      of the cancer.

PMID- 17173674
TI  - Characterisation of community acquired non-typhoidal Salmonella from bacteraemia
      and diarrhoeal infections in children admitted to hospital in Nairobi, Kenya.
AB  - BACKGROUND: In sub-Saharan Africa community-acquired non-typhoidal Salmonella
      (NTS) is a major cause of high morbidity and death among children under 5 years
      of age especially from resource poor settings. The emergence of multidrug
      resistance is a major challenge in treatment of life threatening invasive NTS
      infections in these settings. RESULTS: Overall 170 (51.2%) of children presented
      with bacteraemia alone, 28 (8.4%) with gastroenteritis and bacteraemia and 134
      (40.4%) with gastroenteritis alone. NTS serotypes obtained from all the cases
      included S. Typhimurium (196; 59%), S. Enteritidis (94; 28.3%) and other
      serotypes in smaller numbers (42; 12.7%); distribution of these serotypes among
      cases with bacteremia or gastroenteritis was not significantly different. A
      significantly higher proportion of younger children (< 3 years of age) and those
      from the slums presented with invasive NTS compared to older children and those
      from upper socio-economic groups (p < 0.001). One hundred and forty-seven (44.3%)
      NTS were resistant to 3 or more antibiotics, and out of these 59% were resistant
      to ampicillin, chloramphenicol and tetracycline. There was no significant
      difference in antibiotic resistance between the two serotypes, S. Typhimurium and
      S. Enteritidis. Ceftriaxone and ciprofloxacin were the only antibiotics tested to
      which all the NTS were fully susceptible. Using Pulsed Field Gel Electrophoresis
      (PFGE) there were 3 main patterns of S. Typhimurium and 2 main patterns of S.
      Enteritidis among cases of bacteraemia and gastroenteritis. CONCLUSION: Serotype
      distribution, antibiotic susceptibility and PFGE patterns of NTS causing
      bacteraemia and gastroenteritis did not differ significantly. The high prevalence
      of NTS strains resistant to most of the commonly used antimicrobials is of major
      public health concern.

PMID- 17173675
TI  - Caregivers' perceived treatment failure in home-based management of fever among
      Ugandan children aged less than five years.
AB  - BACKGROUND: Home-based management of fever (HBMF) could improve prompt access to
      antimalarial medicines for African children. However, the perception of treatment
      failure by caregivers has not been assessed. METHODS: Caregiver's perceived
      treatment outcome in HBMF and in alternative sources of fever treatment was
      assessed in a rural Ugandan setting using nine hundred and seventy eight (978)
      caregivers of children between two and 59 months of age, who had reported fever
      within two weeks prior to the study. RESULTS: Lower caregivers' perceived
      treatment failure (15% and 23%) was observed in the formal health facilities and
      in HBMF, compared to private clinics (38%), drug shops (55%) or among those who
      used herbs (56%). Under HBMF, starting treatment within 24 hours of symptoms
      onset and taking treatment for the recommended three days duration was associated
      with a lower perceived treatment failure. Conversely, vomiting, convulsions and
      any illness in the month prior to the fever episode was associated with a higher
      perceived treatment failure. CONCLUSION: In this medium malaria transmission
      setting, caregiver's perceived treatment outcome was better in HBMF compared to
      alternative informal sources of treatment.

PMID- 17173676
TI  - Working memory deficits in adults with ADHD: is there evidence for subtype
      differences?
AB  - BACKGROUND: Working memory performance is important for maintaining functioning
      in cognitive, academic and social activities. Previous research suggests there
      are prevalent working memory deficits in children with attention deficit
      hyperactivity disorder (ADHD). There is now a growing body of literature
      characterizing working memory functioning according to ADHD subtypes in children.
      The expression of working memory deficits in adults with ADHD and how they vary
      according to subtype, however, remains to be more fully documented. METHODS: This
      study assessed differences in working memory functioning between Normal Control
      (NC) adults (N = 18); patients with ADHD, Combined (ADHD-CT) Type ADHD (N = 17);
      and ADHD, Inattentive (ADHD-IA) Type (N = 16) using subtests from the Wechsler
      Adult Intelligence Scale-III and Wechsler Memory Scale-III and the Paced Auditory
      Serial Addition Task (PASAT). RESULTS: The ADHD groups displayed significant
      weaknesses in contrast to the NC group on working memory tests requiring rapid
      processing and active stimulus manipulation. This included the Letter-Number
      Sequencing test of the Wechsler scales, PASAT omission errors and the longest
      sequence of consecutive correct answers on the PASAT. No overall ADHD group
      subtype differences emerged; however differences between the ADHD groups and the
      NC group varied depending on the measure and the gender of the participants.
      Gender differences in performance were evident on some measures of working
      memory, regardless of group, with males performing better than females.
      CONCLUSION: In general, the data support a dimensional interpretation of working
      memory deficits experienced by the ADHD-CT and ADHD-IA subtypes, rather than an
      absolute difference between subtypes. Future studies should test the effects of
      processing speed and load on subtype performance and how those variables interact
      with gender in adults with ADHD.

PMID- 17173677
TI  - Disease burden and related medical costs of rotavirus infections in Taiwan.
AB  - BACKGROUND: The disease burden and associated medical costs of rotavirus
      infections in inpatient and outpatient sectors in Taiwan were examined in
      anticipation of the availability of new rotavirus vaccines. METHODS: The yearly
      national case number and medical costs for all for inpatients and outpatients
      with acute gastroenteritis (AGE) were extracted from the Bureau of National
      Health Insurance database in Taiwan according to ICD-9-CM codes. A retrospective
      study was also performed using records of children with AGE seen at three
      hospitals in Taiwan in 2001 to identify laboratory confirmed rotavirus infection
      cases. The annual incidence and related medical costs of AGE due to rotavirus
      infection were then estimated. RESULTS: Children <5 years old comprised 83.6% of
      inpatient and 62.0% of outpatient pediatric AGE cases in Taiwan in 2001.
      Rotavirus was the most common agent detected among AGE patients in this age group
      in the three hospitals, and was detected in 32.9% (221/672) of inpatient and 24%
      (23/96) of outpatient stool specimens tested for microbial etiologies. An
      estimated 277,400 to 624,892 cases of rotavirus infections sought medical care in
      Taiwan in 2001, equaling one in 2 to 5 children <5 years old required medical
      care due to rotavirus infection. The incidence of hospitalization due to
      rotavirus infections was 1,528-1,997/100,000 for children <5 years old. The total
      associated medical costs due to rotavirus infection were estimated at US $10-16
      millions in Taiwan in 2001. Although the per-capita medical cost of rotavirus
      infection was lower in Taiwan than in the United States or Hong Kong, the
      personal economic burden was similar among the three places when normalized for
      gross national incomes per capita. CONCLUSION: Infections caused by rotavirus
      constitute an important human and economic burden among young children in Taiwan.
      A safe and effective vaccine is urgently needed.

PMID- 17173678
TI  - Modification of the mycobacteriophage Ms6 attP core allows the integration of
      multiple vectors into different tRNAala T-loops in slow- and fast-growing
      mycobacteria.
AB  - BACKGROUND: Mycobacteriophage Ms6 integrates into Mycobacterium smegmatis and M.
      bovis BCG chromosome at the 3' end of tRNAala genes. Homologous recombination
      occurs between the phage attP core and the attB site located in the T-loop.
      Integration-proficient vectors derived from Ms6 are useful genetic tools, but
      their insertion sites in the BCG chromosome remain poorly defined. The primary
      objective of this study was to identify Ms6 target genes in M. smegmatis and BCG.
      We then aimed to modify the attP site in Ms6-derived vectors, to switch
      integration to other tRNAala loci. This provided the basis for the development of
      recombinant M. bovis BCG strains expressing several reporter genes inserted into
      different tRNAala genes. RESULTS: The three tRNAala genes are highly conserved in
      M. smegmatis and BCG. However, in the T-loop of tRNAalaU and tRNAalaV containing
      the attB site, a single base difference was observed between the two species. We
      observed that the tRNAalaU gene was the only site into which Ms6-derived
      integration-proficient vectors integrated in M. smegmatis, whereas in BCG, the
      tRNAalaV gene was used as the target. No integration occurred in the BCG tRNAalaU
      T-loop, despite a difference of only one base from the 26-base Ms6 attP core. We
      mutated the attP core to give a perfect match with the other tRNAala T-loops from
      M. smegmatis and BCG. Modification of the seven-base T-loop decreased integration
      efficiency, identifying this site as a possible site of strand exchange. Finally,
      two Ms6 vectors were constructed to integrate two reporter genes into the
      tRNAalaU and tRNAalaV T-loops of the same BCG chromosome. CONCLUSION: Small
      changes in the 7 bp T-loop attP site of Ms6 made it possible to use another attB
      site, albeit with a lower integration efficiency. These molecular studies on BCG
      tRNAala genes made it possible to create valuable tools for the site-directed
      insertion of several genes in the same BCG strain. These tools will be useful for
      the development of novel multivalent vaccines and genetic studies.

PMID- 17173679
TI  - Adherence to cardioprotective medications and mortality among patients with
      diabetes and ischemic heart disease.
AB  - BACKGROUND: Patients with diabetes and ischemic heart disease (IHD) are at high
      risk for adverse cardiac outcomes. Clinical practice guidelines recommend
      multiple cardioprotective medications to reduce recurrent events. We evaluated
      the association between cardioprotective medication adherence and mortality among
      patients with diabetes and IHD. METHODS: In a retrospective cohort study of 3,998
      patients with diabetes and IHD, we evaluated use of ACE inhibitors or angiotensin
      receptor blockers, beta-blockers, and statin medications. Receipt of
      cardioprotective medications was based on filled prescriptions. Medication
      adherence was calculated as the proportion of days covered (PDC) for filled
      prescriptions. The primary outcome of interest was all-cause mortality. RESULTS:
      The majority of patients (92.8%) received at least 1 cardioprotective medication.
      Patients receiving any medications had lower unadjusted mortality rates compared
      to patients not receiving any medications (7.9% vs. 11.5%; p = 0.03). In
      multivariable analysis, receipt of any cardioprotective medication remained
      associated with lower all-cause mortality (OR 0.65; 95% CI 0.43-0.99). Among
      patients receiving cardioprotective medications, the majority (80.3%) were
      adherent (PDC > or = 0.80). Adherent patients had lower unadjusted mortality
      rates (6.7% vs. 12.1%; p < 0.01). In multivariable analysis, medication adherence
      remained associated with lower all-cause mortality (OR 0.52; 95% CI 0.39-0.69)
      compared to non-adherence. In contrast, there was no mortality difference between
      patients receiving cardioprotective medications who were non-adherent compared to
      patients not receiving any medications (OR 1.01; 95% CI 0.64-1.61). CONCLUSION:
      In conclusion, medication adherence is associated with improved outcomes among
      patients with diabetes and IHD. Quality improvement interventions are needed to
      increase medication adherence in order for patients to maximize the benefit of
      cardioprotective medications.

PMID- 17173680
TI  - Microcirculatory alterations induced by sedation in intensive care patients.
      Effects of midazolam alone and in association with sufentanil.
AB  - INTRODUCTION: Sedation is widely used in intensive care unit (ICU) patients to
      limit the risk of pulmonary barotrauma and to decrease oxygen needs. However,
      adverse effects of cc5128sedation have not been fully evaluated; in particular,
      effects of benzodiazepine and opiates on microcirculation have not been
      extensively studied. The aim of this study was to evaluate the microcirculatory
      effects of a sedation protocol commonly prescribed in the ICU. METHODS: Ten non
      septic patients under controlled ventilation requiring sedation for therapeutic
      purposes were enrolled in a prospective observational study conducted in an ICU
      of a university hospital. Sedation was conducted in two successive steps: first,
      each patient received midazolam (0.1 mg/kg per hour after a bolus of 0.05 mg/kg,
      then adapted to reach a Ramsay score of between 3 and 5). Second, after one hour,
      sufentanil was added (0.1 microg/kg per hour after a bolus of 0.1 microg/kg).
      Arterial pressure, heart rate, cardiac output determined by transthoracic
      impedance, transcutaneous oxygen (tcPO2) and carbon dioxide (tcPCO2) pressures,
      and microcirculatory blood flow determined by laser Doppler flowmetry at rest and
      during a reactive hyperaemia challenge were measured before sedation (NS period),
      one hour after midazolam infusion (H period), and one hour after midazolam
      sufentanil infusion (HS period). RESULTS: Arterial pressure decreased in both
      sedation periods, but heart rate, cardiac output, tcPO2, and tcPCO2 remained
      unchanged. In both sedation periods, microcirculatory changes occurred with an
      increase in cutaneous blood flow at rest (H period: 207 +/- 25 perfusion units
      [PU] and HS period: 205 +/- 25 PU versus NS period: 150 +/- 22 PU, p < 0.05),
      decreased response to ischaemia (variation of blood flow to peak: H period: 97 +/
      16 PU and HS period: 73 +/- 9 PU versus NS period: 141 +/- 14 PU, p < 0.05), and
      attenuation of vasomotion. CONCLUSION: Sedation with midazolam or a combination
      of midazolam and sufentanil induces a deterioration of vasomotion and
      microvascular response to ischaemia, raising the question of whether this effect
      may further alter tissue perfusion when already compromised, as in septic
      patients.

PMID- 17173681
TI  - Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal
      cell model.
AB  - BACKGROUND: The plasma membrane scavenger receptor, SR-BI, mediates the
      'selective uptake' process by which cholesteryl esters (CE) from exogenously
      supplied HDL are taken up by target cells. Recent work suggests that dimer and
      higher order oligomeric forms of the SR-BI protein are important to this process.
      SR-BI has been shown to be particularly associated with microvilli and
      microvillar channels found at the cell surface of steroidogenic cells, and a
      study with the hormone stimulated adrenal gland has shown impressive changes in
      the size and complexity of the microvillar compartment as the mass of CE uptake
      (and accompanying steroidogenesis) fluctuates. In the present study, we examine a
      cell line in which we overexpress the SR-BI protein to determine if
      morphological, biochemical and functional events associated with SR-BI in a
      controlled cell system are similar to those observed in the intact mammalian
      adrenal which is responsive to systemic factors. METHODS: Y1-BS1 mouse
      adrenocortical cells were transiently transfected using rat SR-BI-pcDNA6-V5-His,
      rat SR-BI-pcDNA6-cMyc-His or control pcDNA6-V5-His vector construct using a CaPO4
      precipitation technique. Twenty four hours after transfection, cells were treated
      with, or without, Bt2cAMP, and SR-BI expression, CE uptake, and steroidogenesis
      was measured. SR-BI dimerization and cell surface architectural changes were
      assessed using immunoelectron microscopic techniques. RESULTS: Overexpression of
      the scavenger receptor protein, SR-BI, in Y1-BS1 cells results in major
      alterations in cell surface architecture designed to increase uptake of HDL
      supplied-CEs. Changes include 1 the formation of crater-like erosions of the
      surface with multiple double membraned channel structures lining the craters, and
      2 dimerized formations of SR-BI lining the newly formed craters and associated
      double membraned channels. CONCLUSION: These data show that overexpression of the
      scavenger receptor protein, SR-BI (accompanied by suitable hormone treatment and
      lipoproteins) in susceptible mammalian cells - is associated with increased
      cholesterol uptake and SR-BI dimerization within a much enlarged and
      architecturally complex microvillar compartment. These changes duplicate the
      structural, biochemical and functional changes related to the uptake of HDL CEs
      normally signaled by the action of ACTH on intact adrenal tissue.

PMID- 17173684
TI  - Effect of various normalization methods on Applied Biosystems expression array
      system data.
AB  - BACKGROUND: DNA microarray technology provides a powerful tool for characterizing
      gene expression on a genome scale. While the technology has been widely used in
      discovery-based medical and basic biological research, its direct application in
      clinical practice and regulatory decision-making has been questioned. A few key
      issues, including the reproducibility, reliability, compatibility and
      standardization of microarray analysis and results, must be critically addressed
      before any routine usage of microarrays in clinical laboratory and regulated
      areas can occur. In this study we investigate some of these issues for the
      Applied Biosystems Human Genome Survey Microarrays. RESULTS: We analyzed the gene
      expression profiles of two samples: brain and universal human reference (UHR), a
      mixture of RNAs from 10 cancer cell lines, using the Applied Biosystems Human
      Genome Survey Microarrays. Five technical replicates in three different sites
      were performed on the same total RNA samples according to manufacturer's standard
      protocols. Five different methods, quantile, median, scale, VSN and cyclic loess
      were used to normalize AB microarray data within each site. 1,000 genes spanning
      a wide dynamic range in gene expression levels were selected for real-time PCR
      validation. Using the TaqMan assays data set as the reference set, the
      performance of the five normalization methods was evaluated focusing on the
      following criteria: (1) Sensitivity and reproducibility in detection of
      expression; (2) Fold change correlation with real-time PCR data; (3) Sensitivity
      and specificity in detection of differential expression; (4) Reproducibility of
      differentially expressed gene lists. CONCLUSION: Our results showed a high level
      of concordance between these normalization methods. This is true, regardless of
      whether signal, detection, variation, fold change measurements and
      reproducibility were interrogated. Furthermore, we used TaqMan assays as a
      reference, to generate TPR and FDR plots for the various normalization methods
      across the assay range. Little impact is observed on the TP and FP rates in
      detection of differentially expressed genes. Additionally, little effect was
      observed by the various normalization methods on the statistical approaches
      analyzed which indicates a certain robustness of the analysis methods currently
      in use in the field, particularly when used in conjunction with the Applied
      Biosystems Gene Expression System.

PMID- 17173683
TI  - TRPV1 antagonists attenuate antigen-provoked cough in ovalbumin sensitized guinea
      pigs.
AB  - We examined the molecular pharmacology and in vivo effects of a TRPV1 receptor
      antagonist, N-(4-Tertiarybutylphenyl)-4(3-cholorphyridin-2-yl)-tetrahydro
      pyrazine1(2H) - carboxamide (BCTC) on the guinea pig TRPV1 cation channel. BCTC
      antagonized capsaicin-induced activation and PMA-mediated activation of guinea
      pig TRPV1 with IC50 values of 12.2 +/- 5.2 nM, and 0.85 +/- 0.10 nM,
      respectively. In addition, BCTC (100 nM) completely blocked the ability of
      heterologously expressed gpTRPV1 to respond to decreases in pH. Thus, BCTC is
      able to block polymodal activation of gpTRPV1. Furthermore, in nodose ganglia
      cells, capsaicin induced Ca2+ influx through TRPV1 channel was inhibited via BCTC
      in a concentration dependent manner. In in vivo studies capsaicin (10 - 300 muM)
      delivered by aerosol to the pulmonary system of non-sensitized guinea pigs
      produced an increase in cough frequency. In these studies, the tussigenic effects
      of capsaicin (300 muM) were blocked in a dose dependent fashion when BCTC (0.01
      3.0 mg/kg, i.p.) was administered 30 minutes before challenge. The high dose of
      BCTC (3.0 mg/kg, i.p) produced a maximum inhibition of capsaicin-induced cough of
      65%. We also studied the effects of BCTC (0.03 and 3.0) when administered 60
      minutes before capsaicin. Under these conditions, BCTC (3.0 mg/kg, i.p) produced
      a maximum decrease in capsaicin-induced cough of 31%. In ovalbumin passively
      sensitized guinea pigs, we found that BCTC (1 and 3 mg/kg, i.p.) attenuated
      antigen ovalbumin (0.3%) cough responses by 27% and 60%, respectively. We
      conclude that TRPV1 channel activation may play role in cough mediated by antigen
      in sensitized guinea pigs. Our results supports increasing evidence that TRPV1
      may play a role in the generation of the cough response.

PMID- 17173685
TI  - Transcription profile of a human breast cancer cell line expressing MMTV-like
      sequences.
AB  - BACKGROUND: It has been postulated that inflammation caused by certain viruses
      might result in cancer. Recently, it was shown that childhood lymphoblastic
      leukemia, breast and ovarian cancers express an interferon-related signature,
      providing support for this notion. We have previously shown that 38% of the
      sporadic breast cancers contain MMTV-like env gene sequences. To find out if the
      presence and expression of MMTV-like sequences correlated with an inflammatory
      phenotype, we have compared the expression profile of two sublines of MCF-7
      cells, one containing the MMTV-like sequences (env+), the other one lacking them
      (env-). RESULTS: The results indicated that there were 47 differentially
      expressed genes between the two sublines. Among 27 upregulated genes in the env+
      cells there were 7 interferon-related genes, 5 TNF-connected genes and 2 TGFbeta
      related genes. CONCLUSION: These results suggest that the env+ cells were most
      likely responding to an infectious agent, and support the hypothesis that a viral
      infection may play a role in breast cancer pathogenesis.

PMID- 17173682
TI  - Etiological study of esophageal squamous cell carcinoma in an endemic region: a
      population-based case control study in Huaian, China.
AB  - BACKGROUND: Continuous exposure to various environmental carcinogens and genetic
      polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many
      types of human cancers, including esophageal squamous cell carcinoma (ESCC).
      Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been
      done in characterizing the risk factors of ESCC in this area. The aims of this
      study is to evaluate the etiological roles of demographic parameters,
      environmental and food-borne carcinogens exposure, and XME polymorphisms in
      formation of ESCC, and to investigate possible gene-gene and gene-environment
      interactions associated with ESCC in Huaian, China. METHODS: A population based
      case-control study was conducted in 107 ESCC newly diagnosed cases and 107
      residency- age-, and sex-matched controls in 5 townships of Huaian. In addition
      to regular epidemiological and food frequency questionnaire analyses, genetic
      polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II
      enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were
      assessed from genomic DNA using PCR based techniques. RESULTS: Consuming acrid
      food, fatty meat, moldy food, salted and pickled vegetables, eating fast,
      introverted personality, passive smoking, a family history of cancer, esophageal
      lesion, and infection with Helicobacter pylori were significant risk factors for
      ESCC (P < 0.05). Regular clean up of food storage utensils, green tea
      consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01).
      The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to
      controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI)
      from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22-6.25;
      P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1,
      CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05). CONCLUSION: Our
      results demonstrated that dietary and environmental exposures, some demographic
      parameters and genetic polymorphism of GSTT1 may play important roles in the
      development of ESCC in Huaian area, China.

PMID- 17173687
TI  - Sciatic neuropathy following endovascular treatment of a limb vascular
      malformation.
AB  - BACKGROUND: Endovascular therapy for vascular malformations is one of the
      treatment options for limb vascular malformations. CASE PRESENTATION: A patient
      with a vascular malformation of the hip developed ipsilateral leg weakness
      immediately after endovascular embolization and sclerotherapy. Clinical and
      electrodiagnostic findings later confirmed an incomplete sciatic neuropathy.
      CONCLUSION: We propose that endovascular treatment compromised the patient's
      sciatic nerve either through direct neurotoxicity of the sclerosing agent or
      ischemic injury.

PMID- 17173686
TI  - ICD-10 coding algorithms for defining comorbidities of acute myocardial
      infarction.
AB  - BACKGROUND: With the introduction of ICD-10 throughout Canada, it is important to
      ensure that Acute Myocardial Infarction (AMI) comorbidities employed in risk
      adjustment methods remain valid and robust. Therefore, we developed ICD-10 coding
      algorithms for nine AMI comorbidities, examined the validity of the ICD-10 and
      ICD-9 coding algorithms in detection of these comorbidities, and assessed their
      performance in predicting mortality. The nine comorbidities that we examined were
      shock, diabetes with complications, congestive heart failure, cancer,
      cerebrovascular disease, pulmonary edema, acute renal failure, chronic renal
      failure, and cardiac dysrhythmias. METHODS: Coders generated a comprehensive list
      of ICD-10 codes corresponding to each AMI comorbidity. Physicians independently
      reviewed and determined the clinical relevance of each item on the list. To
      ensure that the newly developed ICD-10 coding algorithms were valid in recording
      comorbidities, medical charts were reviewed. After assessing ICD-10 algorithms'
      validity, both ICD-10 and ICD-9 algorithms were applied to a Canadian provincial
      hospital discharge database to predict in-hospital, 30-day, and 1-year mortality.
      RESULTS: Compared to chart review data as a 'criterion standard', ICD-9 and ICD
      10 data had similar sensitivities (ranging from 7.1-100%), and specificities
      (above 93.6%) for each of the nine AMI comorbidities studied. The frequencies for
      the comorbidities were similar between ICD-9 and ICD-10 coding algorithms for
      49,861 AMI patients in a Canadian province during 1994-2004. The C-statistics for
      predicting 30-day and 1 year mortality were the same for ICD-9 (0.82) and for ICD
      10 data (0.81). CONCLUSION: The ICD-10 coding algorithms developed in this study
      to define AMI comorbidities performed similarly as past ICD-9 coding algorithms
      in detecting conditions and risk-adjustment in our sample. However, the ICD-10
      coding algorithms should be further validated in external databases.

PMID- 17173688
TI  - Eg5 steps it up!
AB  - Understanding how molecular motors generate force and move microtubules in
      mitosis is essential to understanding the physical mechanism of cell division.
      Recent measurements have shown that one mitotic kinesin superfamily member, Eg5,
      is mechanically processive and capable of crosslinking and sliding microtubules
      in vitro. In this review, we highlight recent work that explores how Eg5
      functions under load, with an emphasis on the nanomechanical properties of single
      enzymes.

PMID- 17173689
TI  - Investigation of the molecular profile of basal cell carcinoma using whole genome
      microarrays.
AB  - BACKGROUND: Skin cancer accounts for 1/3 of all newly diagnosed cancer. Although
      seldom fatal, basal cell carcinoma (BCC) is associated with severe disfigurement
      and morbidity. BCC has a unique interest for researchers, as although it is often
      locally invasive, it rarely metastasises. This paper, reporting the first whole
      genome expression microarray analysis of skin cancer, aimed to investigate the
      molecular profile of BCC in comparison to non-cancerous skin biopsies. RNA from
      BCC and normal skin specimens was analysed using Affymetrix whole genome
      microarrays. A Welch t-test was applied to data normalised using dCHIP to
      identify significant differentially-expressed genes between BCC and normal
      specimens. Principal component analysis and support vector machine analysis were
      performed on resulting genelists, Genmapp was used to identify pathways affected,
      and GOstat aided identification of areas of gene ontology more highly represented
      on these lists than would be expected by chance. RESULTS: Following
      normalisation, specimens clustered into groups of BCC specimens and of normal
      skin specimens. Of the 54,675 gene transcripts/variants analysed, 3,921 were
      differentially expressed between BCC and normal skin specimens. Of these, 2,108
      were significantly up-regulated and 1,813 were statistically significantly down
      regulated in BCCs. CONCLUSION: Functional gene sets differentially expressed
      include those involved in transcription, proliferation, cell motility, apoptosis
      and metabolism. As expected, members of the Wnt and hedgehog pathways were found
      to be significantly different between BCC and normal specimens, as were many
      previously undescribed changes in gene expression between normal and BCC
      specimens, including basonuclin2 and mrp9. Quantitative-PCR analysis confirmed
      our microarray results, identifying novel potential biomarkers for BCC.

PMID- 17173690
TI  - A hierarchy of effective teaching and learning to acquire competence in evidenced
      based medicine.
AB  - BACKGROUND: A variety of methods exists for teaching and learning evidence-based
      medicine (EBM). However, there is much debate about the effectiveness of various
      EBM teaching and learning activities, resulting in a lack of consensus as to what
      methods constitute the best educational practice. There is a need for a clear
      hierarchy of educational activities to effectively impart and acquire competence
      in EBM skills. This paper develops such a hierarchy based on current empirical
      and theoretical evidence. DISCUSSION: EBM requires that health care decisions be
      based on the best available valid and relevant evidence. To achieve this,
      teachers delivering EBM curricula need to inculcate amongst learners the skills
      to gain, assess, apply, integrate and communicate new knowledge in clinical
      decision-making. Empirical and theoretical evidence suggests that there is a
      hierarchy of teaching and learning activities in terms of their educational
      effectiveness: Level 1, interactive and clinically integrated activities; Level
      2(a), interactive but classroom based activities; Level 2(b), didactic but
      clinically integrated activities; and Level 3, didactic, classroom or standalone
      teaching. SUMMARY: All health care professionals need to understand and implement
      the principles of EBM to improve care of their patients. Interactive and
      clinically integrated teaching and learning activities provide the basis for the
      best educational practice in this field.

PMID- 17173691
TI  - Fundamental difference in life history traits of two species of Cataglyphis ants.
AB  - BACKGROUND: The two sympatric species of Tunisian desert ants, Cataglyphis
      bicolor and C. mauritanica, do not exhibit any differences in their foraging
      ecology, e.g. in food preferences and in their spatial and temporal activity
      patterns. Here we show that instead the two species markedly differ in their life
      histories. RESULTS: We analysed mtDNA of specimens that were collected along a
      250-km transect. C. bicolor exhibited a genetically unstructured population (with
      the genetic and geographic distances among colonies not being correlated). On the
      contrary the populations of the polygynous C. mauritanica were clearly
      structured, i.e. exhibited a strong correlation between genetic and geographic
      distances. This difference is in accordance with large queen dispersal distances
      due to far-reaching mating flights in C. bicolor and small queen dispersal
      distances due to colony foundation by budding in C. mauritanica. Furthermore,
      wherever we found populations of both species to coexist within the same habitat,
      the habitat was used agriculturally. Mapping nest positions over periods of
      several years showed that plowing dramatically decreased the nest densities of
      either species. CONCLUSION: We conclude that owing to its greater queen dispersal
      potential C. bicolor might be more successful in quickly re-colonizing disturbed
      areas, while the slowly dispersing C. mauritanica could later out-compete C.
      bicolor by adopting its effective nest-budding strategy. According to this
      scenario the observed sympatry of the two species might be an intermediate stage
      in which faster colonization by one species and more powerful exploitation of
      space by the other species have somehow balanced each other out. In conclusion,
      C. bicolor and C. mauritanica represent an example where environmental
      disturbances in combination with different life histories might beget sympatry in
      congeneric species with overlapping niches.

PMID- 17173692
TI  - iHOPerator: user-scripting a personalized bioinformatics Web, starting with the
      iHOP website.
AB  - BACKGROUND: User-scripts are programs stored in Web browsers that can manipulate
      the content of websites prior to display in the browser. They provide a novel
      mechanism by which users can conveniently gain increased control over the content
      and the display of the information presented to them on the Web. As the Web is
      the primary medium by which scientists retrieve biological information, any
      improvements in the mechanisms that govern the utility or accessibility of this
      information may have profound effects. GreaseMonkey is a Mozilla Firefox
      extension that facilitates the development and deployment of user-scripts for the
      Firefox web-browser. We utilize this to enhance the content and the presentation
      of the iHOP (information Hyperlinked Over Proteins) website. RESULTS: The
      iHOPerator is a GreaseMonkey user-script that augments the gene-centred pages on
      iHOP by providing a compact, configurable visualization of the defining
      information for each gene and by enabling additional data, such as biochemical
      pathway diagrams, to be collected automatically from third party resources and
      displayed in the same browsing context. CONCLUSION: This open-source script
      provides an extension to the iHOP website, demonstrating how user-scripts can
      personalize and enhance the Web browsing experience in a relevant biological
      setting. The novel, user-driven controls over the content and the display of Web
      resources made possible by user-scripts, such as the iHOPerator, herald the
      beginning of a transition from a resource-centric to a user-centric Web
      experience. We believe that this transition is a necessary step in the
      development of Web technology that will eventually result in profound
      improvements in the way life scientists interact with information.

PMID- 17173693
TI  - Training competent and effective Primary Health Care Workers to fill a void in
      the outer islands health service delivery of the Marshall Islands of Micronesia.
AB  - BACKGROUND: Human resources for health are non-existent in many parts of the
      world and the outer islands of Marshall Islands in Micronesia are prime examples.
      While the more populated islands with hospital facilities are often successful in
      recruiting qualified health professionals from overseas, the outer islands
      generally have very limited health resources, and are thus less successful. In an
      attempt to provide reasonable health services to these islands, indigenous people
      were trained as Health Assistants (HA) to service their local communities. In an
      effort to remedy the effectiveness of health care delivery to these islands, a
      program to train mid-level health care workers (Hospital Assistants) was
      developed and implemented by the Ministry of Health in conjunction with the
      hospital in Majuro, the capital city of the Marshall Islands. METHODS: A
      physician instructor with experience and expertise in primary health care in
      these regions conducted the program. The curriculum included training in basic
      health science, essentials of endemic disorders and their clinical management
      appropriate to the outer islands. Emphasis was given to prevention and health
      promotion as well as to the curative aspects. For clinical observation, the
      candidates were assigned to clinical departments of the Majuro hospital for 1
      year during their training, as assistants to the nursing staff. This paper
      discusses the details of the training, the modalities used to groom the
      candidates, and an assessment of the ultimate effectiveness of the program.
      RESULTS: Out of 16 boys who began training, 14 candidates were successful in
      completing the program. In 1998 a similar program was conducted exclusively for
      women under the auspices of Asian Development Bank funding, hence women were not
      part of this program. CONCLUSION: For developing countries of the Pacific,
      appropriately trained human resources are an essential component of economic
      progress, and the health workforce is an important part of human resources for
      sustainable progress and development.

PMID- 17173694
TI  - Phase II trial of sequential gefitinib after minor response or partial response
      to chemotherapy in Chinese patients with advanced non-small-cell lung cancer.
AB  - BACKGROUND: Basic research of gefitinib (Iressa, ZD1839) has demonstrated the
      combination effects of gefitinib and chemotherapy were sequence-dependent. To
      evaluate the efficacy of sequential administration of gefitinib following a minor
      response or partial response to two to three cycles of chemotherapy, a phase II
      clinical trial was done in Chinese patients with advanced non-small-cell lung
      cancer (NSCLC). METHODS: Thirty-three consecutive patients with advanced NSCLC
      that had been pretreated with at least one chemotherapeutic regimen and were
      responding to chemotherapy following 2 to 3 cycles of treatment, entered the
      trial from May 2004 to February 2006. Patients received gefitinib at an oral dose
      of 250 mg once daily for 4 weeks. RESULTS: Thirty-three patients were evaluable
      for response and toxicity. The objective response rate was 24.2% (8 of 33) (95%
      CI, 11% to 42%). The symptom improvement rate was 54.5% (18 of 33) (95% CI, 41%
      to 69%). The median duration of response was 7 months (95%CI, 4.0 to 13.2
      months). The median time to disease progression (TTP) was 6.5 months (95%CI, 0.7
      to 16.6 months). The median overall survival time (OS) was 9.8 months (range, 2.1
      to 18.0 months), and the actuarial 1-year survival was 36.4%. Toxicity was
      relatively mild and included only one patient (3.0%) with grade 4 diarrhea, 1
      (3.0%) with grade 3 rash, 1 (3.0%) with grade 3 nausea, and 1 with grade 3
      vomiting (3.0%). CONCLUSION: Preliminary results suggest that sequential
      administration of gefitinib following a response to chemotherapy may be
      beneficial for Chinese patients with advanced NSCLC. Further randomized clinical
      trials are needed.

PMID- 17173695
TI  - Constructing indices representing supportiveness of the physical environment for
      walking using the Rasch measurement model.
AB  - BACKGROUND: The objectives of this study were to use the Rasch model to 1) assess
      the psychometric properties of a physical environmental audit instrument and 2)
      to develop indices of interrelated environmental attributes that summarize
      environmental supportiveness for walking. METHODS: A set of items were derived
      representing two conceptual physical environmental constructs: 1)
      functional/safety, and; 2) aesthetics. Ad hoc criteria based on point-biserial
      and Rasch-based fit statistics were used to examine the construct validity and
      internal reliability of the two constructs. RESULTS: The Rasch-based fit
      statistics assisted in identifying 12 items that belonged to the
      functional/safety construct and 4 items that belonged to the aesthetic construct.
      The reliability of the two constructs were low to moderate (functional/safety
      r(beta) = 0.19 and aesthetics r(beta) = 0.35). CONCLUSION: Given the vast number
      of built environmental attributes, a means of developing summary indices is
      essential. Future studies should assess the reliability and validity of indices
      that summarize physical environmental characteristics conducive to walking before
      testing them in predictive models of physical activity. More research examining
      procedures for measuring the built environment and techniques for analyzing
      environmental data are needed to guide future research in this area.

PMID- 17173696
TI  - Tear secretion dysfunction among women workers engaged in light-on tests in the
      TFT-LCD industry.
AB  - BACKGROUND: The TFT-LCD (thin film transistor liquid crystal display) industry is
      rapidly growing in Taiwan and many other countries. A large number of workers,
      mainly women, are employed in the light-on test process to detect the defects of
      products. At the light-on test workstation, the operator is generally exposed to
      low humidity (in the clean room environment), flashing light, and low ambient
      illumination for long working hours. Many workers complained about eye
      discomfort, and therefore we conducted a study to evaluate the tear secretion
      function of light-on test workers of a TFT-LCD company. METHODS: We recruited
      workers engaged in light-on tests in the company during their periodical health
      examination. In addition to a questionnaire survey of demographic characteristics
      and ophthalmic symptoms, we evaluated the tear secretion function of both eyes of
      each participant using the Schirmer's lacrimal basal secretion test with
      anaesthesia. A participant with one or both eyes yielding abnormal test results
      was defined as a case of tear secretion dysfunction. RESULTS: During the study
      period, a total of 371 light-on test workers received the health examination at
      the clinic of the park, and 52 of them were excluded due to having ophthalmic
      diseases and other systemic diseases that may affect ophthalmic function. All the
      remaining 319 qualified workers agreed to participate in this study, and they
      were all females working by 4-shift rotations. The average age was 24.2 years old
      (standard deviation [SD] = 3.8), and the average employment duration was 13.6
      months (SD = 5.7). Among the 11 ophthalmic symptoms evaluated, eye dryness was
      the most prevalent (prevalence = 43.3%). In addition, the prevalence of tear
      secretion dysfunction in at least one eye was 40.1% (128 cases), and contact lens
      users had an odds ratio of 1.73 (95% confidence interval = 1.02-2.94) in
      comparison with non-contact lens users. Comparing the Schirmer's test results of
      those who also participated in the screening in the previous year, we found 40 of
      the 156 participants (17.2%) with normal test results in the previous year turned
      abnormal in 2001. In contrast, only 21 of the 76 participants (9.1%) with
      abnormal test results in the previous year turned normal, and the difference was
      statistically significant (p = 0.02 for McNemar's test). CONCLUSION: The
      prevalence of tear secretion dysfunction in woman workers engaged in light-on
      tests is high and increases with a one-year duration of employment. The use of
      contact lens may further increase the risk.

PMID- 17173697
TI  - RINGdb: an integrated database for G protein-coupled receptors and regulators of
      G protein signaling.
AB  - BACKGROUND: Many marketed therapeutic agents have been developed to modulate the
      function of G protein-coupled receptors (GPCRs). The regulators of G-protein
      signaling (RGS proteins) are also being examined as potential drug targets. To
      facilitate clinical and pharmacological research, we have developed a novel
      integrated biological database called RINGdb to provide comprehensive and
      organized RGS protein and GPCR information. RESULTS: RINGdb contains information
      on mutations, tissue distributions, protein-protein interactions,
      diseases/disorders and other features, which has been automatically collected
      from the Internet and manually extracted from the literature. In addition, RINGdb
      offers various user-friendly query functions to answer different questions about
      RGS proteins and GPCRs such as their possible contribution to disease processes,
      the putative direct or indirect relationship between RGS proteins and GPCRs.
      RINGdb also integrates organized database cross-references to allow users direct
      access to detailed information. The database is now available at
      http://ringdb.csie.ncu.edu.tw/ringdb/. CONCLUSION: RINGdb is the only integrated
      database on the Internet to provide comprehensive RGS protein and GPCR
      information. This knowledge base will be useful for clinical research, drug
      discovery and GPCR signaling pathway research.

PMID- 17173699
TI  - Is inflammaging an auto[innate]immunity subclinical syndrome?
AB  - The low-grade, chronic, systemic inflammatory state that characterizes the aging
      process (inflammaging) results from late evolutive-based expression of the innate
      immune system. Inflammaging is characterized by the complex set of five
      conditions which can be described as 1. low-grade, 2. controlled, 3.
      asymptomatic, 4. chronic, 5. systemic, inflammatory state, and fits with the
      antagonistic pleiotropy theory on the evolution of aging postulating that
      senescence is the late deleterious effect of genes (pro-inflammatory versus anti
      inflammatory) that are beneficial in early life. Evolutionary programming of the
      innate immune system may act via selection on these genetic traits. Here I
      propose that the already acquired knowledge in this field may pave the way to a
      new chapter in the pathophysiology of autoimmunity: the auto-innate-immunity
      syndromes. Indeed, differently from the well known chapter of conventional
      autoimmune diseases and syndromes where the main actor is the adaptive immunity,
      inflammaging may constitute the subclinical paradigm of a new chapter of
      autoimmunity, namely that arising from an autoimmune inflammatory response of the
      innate-immune-system, an old actor of immunity and yet a new actor of
      autoimmunity, also acting as a major determinant of elderly frailty and age
      associated diseases.

PMID- 17173698
TI  - Mutations underlying 3-hydroxy-3-methylglutaryl CoA lyase deficiency in the Saudi
      population.
AB  - BACKGROUND: 3-hydroxy-3-methylglutaric aciduria (3HMG, McKusick: 246450) is an
      autosomal recessive branched chain organic aciduria caused by deficiency of the
      enzyme 3-Hydroxy-3-Methylglutaryl CoA lyase (HL, HMGCL, EC 4.1.3.4). HL is
      encoded by HMGCL gene and many mutations have been reported. 3HMG is commonly
      observed in Saudi Arabia. METHODS: We utilized Whole Genome Amplification (WGA),
      PCR and direct sequencing to identify mutations underlying 3HMG in the Saudi
      population. Two patients from two unrelated families and thirty-four 3HMG
      positive dried blood spots (DBS) were included. RESULTS: We detected the common
      missense mutation R41Q in 89% of the tested alleles (64 alleles). 2 alleles
      carried the frame shift mutation F305fs (-2) and the last two alleles had a novel
      splice site donor IVS6+1G>A mutation which was confirmed by its absence in more
      than 100 chromosomes from the normal population. All mutations were present in a
      homozygous state, reflecting extensive consanguinity. The high frequency of R41Q
      is consistent with a founder effect. Together the three mutations described
      account for >94% of the pathogenic mutations underlying 3HMG in Saudi Arabia.
      CONCLUSION: Our study provides the most extensive genotype analysis on 3HMG
      patients from Saudi Arabia. Our findings have direct implications on rapid
      molecular diagnosis, prenatal and pre-implantation diagnosis and population based
      prevention programs directed towards 3HMG.

PMID- 17173700
TI  - Multiple pathways contribute to the pathogenesis of Huntington disease.
AB  - Huntington disease (HD) is caused by expansion of a polyglutamine (polyQ) domain
      in the protein known as huntingtin (htt), and the disease is characterized by
      selective neurodegeneration. Expansion of the polyQ domain is not exclusive to
      HD, but occurs in eight other inherited neurodegenerative disorders that show
      distinct neuropathology. Yet in spite of the clear genetic defects and associated
      neurodegeneration seen with all the polyQ diseases, their pathogenesis remains
      elusive. The present review focuses on HD, outlining the effects of mutant htt in
      the nucleus and neuronal processes as well as the role of cell-cell interactions
      in HD pathology. The widespread expression and localization of mutant htt and its
      interactions with a variety of proteins suggest that mutant htt engages multiple
      pathogenic pathways. Understanding these pathways will help us to elucidate the
      pathogenesis of HD and to target therapies effectively.

PMID- 17173701
TI  - Design of the Dutch Obesity Intervention in Teenagers (NRG-DOiT): systematic
      development, implementation and evaluation of a school-based intervention aimed
      at the prevention of excessive weight gain in adolescents.
AB  - BACKGROUND: Only limited data are available on the development, implementation,
      and evaluation processes of weight gain prevention programs in adolescents. To be
      able to learn from successes and failures of such interventions, integral written
      and published reports are needed. METHODS: Applying the Intervention Mapping (IM)
      protocol, this paper describes the development, implementation, and evaluation of
      the Dutch Obesity Intervention in Teenagers (DOiT), a school-based intervention
      program aimed at the prevention of excessive weight gain. The intervention
      focussed on the following health behaviours: (1) reduction of the consumption of
      sugar-sweetened beverages, (2) reduction of energy intake derived from snacks,
      (3) decrease of levels of sedentary behaviour, and (4) increase of levels of
      physical activity (i.e. active transport behaviour and sports participation). The
      intervention program consisted of an individual classroom-based component (i.e.
      an educational program, covering 11 lessons of both biology and physical
      education classes), and an environmental component (i.e. encouraging and
      supporting changes at the school canteens, as well as offering additional
      physical education classes). We evaluated the effectiveness of the intervention
      program using a randomised controlled trial design. We assessed the effects of
      the intervention on body composition (primary outcome measure), as well as on
      behaviour, behavioural determinants, and aerobic fitness (secondary outcome
      measures). Furthermore, we conducted a process evaluation. DISCUSSION: The
      development of the DOiT-intervention resulted in a comprehensive school-based
      weight gain prevention program, tailored to the needs of Dutch adolescents from
      low socio-economic background.

PMID- 17173702
TI  - CyberKnife radiosurgery in the treatment of complex skull base tumors: analysis
      of treatment planning parameters.
AB  - BACKGROUND: Tumors of the skull base pose unique challenges to radiosurgical
      treatment because of their irregular shapes, proximity to critical structures and
      variable tumor volumes. In this study, we investigate whether acceptable
      treatment plans with excellent conformity and homogeneity can be generated for
      complex skull base tumors using the Cyberknife radiosurgical system. METHODS: At
      Georgetown University Hospital from March 2002 through May 2005, the CyberKnife
      was used to treat 80 patients with 82 base of skull lesions. Tumors were
      classified as simple or complex based on their proximity to adjacent critical
      structures. All planning and treatments were performed by the same radiosurgery
      team with the goal of minimizing dosage to adjacent critical structures and
      maximizing target coverage. Treatments were fractionated to allow for safer
      delivery of radiation to both large tumors and tumors in close proximity to
      critical structures. RESULTS: The CyberKnife treatment planning system was
      capable of generating highly conformal and homogeneous plans for complex skull
      base tumors. The treatment planning parameters did not significantly vary between
      spherical and non-spherical target volumes. The treatment parameters obtained
      from the plans of the complex base of skull group, including new conformity
      index, homogeneity index and percentage tumor coverage, were not significantly
      different from those of the simple group. CONCLUSION: Our data indicate that
      CyberKnife treatment plans with excellent homogeneity, conformity and percent
      target coverage can be obtained for complex skull base tumors. Longer follow-up
      will be required to determine the safety and efficacy of fractionated treatment
      of these lesions with this radiosurgical system.

PMID- 17173703
TI  - Gardner's syndrome in a 40-year-old woman: successful treatment of locally
      aggressive desmoid tumors with cytotoxic chemotherapy.
AB  - BACKGROUND: Desmoid tumors that present as a part of Gardener's syndrome can
      present very difficult management problems. CASE PRESENTATION: We report a case
      of intra-abdominal desmoid tumor causing distal small bowel obstruction that
      complicated the management of a more proximal enterocutaneous fistula from the
      jejunum. After failure of more conventional management options including
      imatinib, the patient's disease responded to doxorubicin and ifosfamide. The
      response resolved the bowel obstruction and allowed small intestinal resection to
      resolve the enterocutaneous fistula. CONCLUSION: Systemic cytotoxic therapy with
      doxorubicin and ifosfamide can be useful for patients with complications from
      intra-abdominal desmoid tumor.

PMID- 17173704
TI  - New insight into the structures and formation of anthocyanic vacuolar inclusions
      in flower petals.
AB  - BACKGROUND: Although the biosynthetic pathways for anthocyanins and their
      regulation have been well studied, the mechanism of anthocyanin accumulation in
      the cell is still poorly understood. Different models have been proposed to
      explain the transport of anthocyanins from biosynthetic sites to the central
      vacuole, but cellular and subcellular information is still lacking for
      reconciliation of different lines of evidence in various anthocyanin
      sequestration studies. Here, we used light and electron microscopy to investigate
      the structures and the formation of anthocyanic vacuolar inclusions (AVIs) in
      lisianthus (Eustoma grandiflorum) petals. RESULTS: AVIs in the epidermal cells of
      different regions of the petal were investigated. Three different forms of AVIs
      were observed: vesicle-like, rod-like and irregular shaped. In all cases, EM
      examinations showed no membrane encompassing the AVI. Instead, the AVI itself
      consisted of membranous and thread structures throughout. Light and EM microscopy
      analyses demonstrated that anthocyanins accumulated as vesicle-like bodies in the
      cytoplasm, which themselves were contained in prevacuolar compartments (PVCs).
      The vesicle-like bodies seemed to be transported into the central vacuole through
      the merging of the PVCs and the central vacuole in the epidermal cells. These
      anthocyanin-containing vesicle-like bodies were subsequently ruptured to form
      threads in the vacuole. The ultimate irregular AVIs in the cells possessed a very
      condensed inner and relatively loose outer structure. CONCLUSION: Our results
      strongly suggest the existence of mass transport for anthocyanins from
      biosynthetic sites in the cytoplasm to the central vacuole. Anthocyanin
      containing PVCs are important intracellular vesicles during the anthocyanin
      sequestration to the central vacuole and these specific PVCs are likely derived
      directly from endoplasmic reticulum (ER) in a similar manner to the transport
      vesicles of vacuolar storage proteins. The membrane-like and thread structures of
      AVIs point to the involvement of intravacuolar membranes and/or anthocyanin
      intermolecular association in the central vacuole.

PMID- 17173705
TI  - Severe combined hyperlipidaemia and retinal lipid infiltration in a patient with
      Type 2 diabetes mellitus.
AB  - Severe combined hyperlipidaemia has occasionally been associated with
      infiltration of tissues in addition to arteries and the skin. We report a woman
      with Type 2 diabetes mellitus (DM) and severe combined hyperlipidaemia who
      developed retinal lipid infiltration, resulting in blindness. A 61-year-old woman
      with a 15-year history of Type 2 DM was admitted following a two-week history of
      progressive visual loss. Examination identified lipid infiltration into the
      retina. Phenotypically she had severe combined hyperlipidaemia with elevated IDL
      cholesterol and a broad beta band on lipoprotein electrophoresis, raising the
      possibility of familial dysbetalipoproteinaemia. However, gene sequencing
      analysis indicated that the patient was homozygous for the E3/E3 allele of the
      ApoE gene with no mutations detected in either the coding region or intron-exon
      boundaries. Her lipid profile improved following dietary therapy and gemfibrozil
      treatment, but this had little effect on either her fundal appearances or her
      visual acuity. Type 2 DM plays a vital role both in allowing expression of severe
      combined hyperlipoproteinaemia, in addition to serving as a risk factor for
      complications such as tissue infiltration.

PMID- 17173706
TI  - Psychosocial environment for the integrated education opportunities of the
      disabled in Lithuania.
AB  - BACKGROUND: The policy of the diminution of the social isolation of the disabled
      is the main objective of the strategy of the EU new policy concerning the
      disabled. Lithuanian society faces this objective as well. For this reason, this
      study aiming at providing the theoretical basis for and predicting the possible
      psycho-social environment in an integrated education system, as well as at the
      evaluation of the reasons for the formation of a positive approach to the
      disabled, is especially relevant, since it creates the prerequisites for the
      optimisation of the process of the integration of disabled schoolchildren into
      the general system of education. METHOD: The sample of the study consisted of
      2471 children from the same schools: not integrated (1958), integrated (126) and
      special schools (382). Empirical methods: questionnaire poll, comparative
      analysis. The statistical analysis was carried out using SAS. RESULTS: Our study
      showed that the majority of schoolchildren without disabilities and disabled
      schoolchildren have positive intentions for interpersonal interactions (>82%) and
      positive emotions (>69%) independently of the discrepant character of
      interpersonal contacts, different conditions of education and family life, and
      despite of low level of knowledge. CONCLUSION: The results of the study confirmed
      positive intentions for interpersonal interaction between disabled schoolchildren
      and schoolchildren without disabilities, as well as a positive character of
      emotions, and disprove the unsound myth of the opponents of the social
      integration of the disabled stating that disabled children in comprehensive
      schools would undoubtedly experience offence from their peers without
      disabilities.

PMID- 17173707
TI  - The effect of Bosentan on healing of colonic anastomosis.
AB  - BACKGROUND: Ischemia is the most important factor compromises wound healing in
      colonic anastomosis. Mesenteric vessels are ligated at first while performing
      colonic resection and following anastomosis. Therefore blood supply of the
      related segments of colon temporarily interrupted and ischemia can easily occur.
      This study was carried out to explore whether Bosentan, an endothelin-receptor
      antagonist, can eliminate vasoconstruction, increase blood flow in the splanchnic
      area and anastomotic region and therefore possibly facilitate wound healing and
      prevent intra-abdominal adhesion formation. METHODS: Study is conducted on 30
      female Wistar-Albino rats weighing 180-240 gr. Rats were allocated into three
      groups. Group 1 (n = 10) recevied full-thickness resection of the left colon and
      end-to-end anastomosis. In Groups 2 (n = 10) and 3 (n = 10), vessels of 2-3 cm
      segment of the left colon were ligated, indications of necrosis of that segment
      were expected, followed by resection and end-to-end anastomosis. Two milliliter
      of saline and 5 mg/kg Bosentan was given intraperitoneally in Group 2 and 3,
      respectively. On postoperativ day 6, intra-abdominal adhesions were scored.
      Healing of anastomosis, anastomotic bursting pressures, tissue hydroxyproline
      levels and histopatologically healing scores were assessed. RESULTS: Macroscopic
      adhesion score in Group 3 was lower than the remained groups (p < 0.05). Tissue
      hydroxyproline levels were significantly higher in Group 3 compared to the Groups
      1 and 2 (p < 0.001). Mean anastomotic bursting pressures were 200 mmHg, 164 mmHg
      and 240 mmHg in Groups 1, 2 an 3, respectively (p < 0.05 between Groups 1 and 3;
      p < 0.001 between Groups 2 and 3). Histopathologically, healing scores of Group 1
      were significantly higher than the other groups (p < 0.05 group 1-3, group 2-3).
      CONCLUSION: Bosentan increases anastomotic healing of ischemic colonic
      anastomosis and decreases intra-abdominal adhesion formation.

PMID- 17173708
TI  - Longitudinal patterns of behaviour problems in children with specific speech and
      language difficulties: child and contextual factors.
AB  - BACKGROUND: The purpose of this study was to examine the stability of
      behavioural, emotional and social difficulties (BESD) in children with specific
      speech and language difficulties (SSLD), and the relationship between BESD and
      the language ability. METHODS: A sample of children with SSLD were assessed for
      BESD at ages 8, 10 and 12 years by both teachers and parents. Language abilities
      were assessed at 8 and 10 years. RESULTS: High levels of BESD were found at all
      three ages but with different patterns of trajectories for parents' and teachers'
      ratings. Language ability predicted teacher- but not parent-rated BESD.
      CONCLUSIONS: The study confirms the persistence of high levels of BESD over the
      period 8-12 years and the continuing comorbidity of BESD and language
      difficulties but also indicates a complex interaction of within-child and
      contextual factors over time.

PMID- 17173709
TI  - Grandmother spider: connecting all things.

PMID- 17173710
TI  - Wellness in every stage of life: a new paradigm for public health programs.

PMID- 17173711
TI  - Reducing information pollution in the Internet age.

PMID- 17173712
TI  - Association between physical activity and proximity to physical activity
      resources among low-income, midlife women.
AB  - INTRODUCTION: The association between levels of physical activity and perceived
      and objectively measured proximity to physical activity resources is unclear.
      Clarification is important so that future programs can intervene upon the measure
      with the greatest association. We examined correlations between perceived and
      objectively measured proximity to physical activity resources and then examined
      associations between both measures of proximity and objectively measured physical
      activity. METHODS: Participants (n = 199) were underinsured women from three
      counties in southeastern North Carolina. Perceived proximity to physical activity
      resources (e.g., parks, gyms, schools) was measured using surveys. Objectively
      measured proximity included geographic information systems road network distance
      to the closest resource and existence of resources within 1- and 2-mile buffers
      surrounding participants' homes. To examine the association between proximity to
      resources and activity, the dependent variable in multiple linear regression
      models was the natural logarithm of accelerometer-measured moderate to vigorous
      physical activity in minutes per day. RESULTS: Pearson correlation coefficients
      for perceptions of distance and objectively measured distance to physical
      activity resources ranged from 0.40 (gyms, schools) to 0.54 (parks). Perceived
      distance to gyms and objective number of schools within 1-mile buffers were
      negatively associated with activity. No statistically significant relationships
      were found between activity and perceived or objectively measured proximity to
      parks. CONCLUSION: Results indicate the need for both individual and
      environmental intervention strategies to increase levels of physical activity
      among underinsured, midlife women. More work is needed to determine the most
      effective strategies.

PMID- 17173713
TI  - Case management protocol and declining blood lead concentrations among children.
AB  - INTRODUCTION: Blood lead concentrations among children aged 6 years and younger
      become a concern at 10 microg/dL (0.48 micromol/L) or higher. The authors'
      objective was to determine whether initial blood lead concentrations of 10-19
      microg/dL (0.48-0.96 micromol/L) declined among children aged 3 years and younger
      and whether the magnitude of decline was associated with the case management
      protocol of the state or local childhood lead poisoning prevention program.
      METHODS: The authors analyzed childhood blood lead surveillance data from 1994
      through 1995 and case management protocols from six states that reported the
      results of all blood lead tests. The study included 2109 children aged 2 years or
      younger who had a venous blood lead concentration of 10-19 microg/dL (0.48-0.96
      micromol/L) and a follow-up venous blood lead test within 3 to 12 months.
      RESULTS: Overall, blood lead concentrations increased by 0.25 microg/dL (0.01
      micromol/L) between the time of the initial elevated blood lead test and the
      follow-up test, but concentrations declined by 1.96 microg/dL (0.09 micromol/L)
      among children covered by a case management protocol that included a home visit
      and by 0.92 microg/dL (0.04 micromol/L) among those covered by a protocol that
      included a lead source investigation. The decline remained significant after we
      adjusted for the child's age. CONCLUSION: These findings suggest that childhood
      lead prevention programs should consider focusing their efforts on home visits
      and lead source investigations.

PMID- 17173714
TI  - The epidemic of extreme obesity among American Indian and Alaska Native adults
      with diabetes.
AB  - INTRODUCTION: The purpose of this study was to describe the prevalence of obesity
      among American Indian and Alaska Native (AI/AN) adults with diabetes and to
      examine the temporal trends for class I, II, and III obesity in this high-risk
      group during a 10-year period. METHODS: We used data on body mass index (BMI)
      from the annual Diabetes Care and Outcomes Audit to estimate the prevalence of
      class I, II, and III obesity (class I = 30.0-34.9 kg/m2, class II = 35.0-39.9
      kg/m2, and class III > or = 40.0 kg/m2) in each year from 1995 through 2004. We
      also investigated trends in mean BMI during the 10-year period and the role of
      treatment in these trends using multivariable linear regression models. RESULTS:
      Obesity was highly prevalent in this population in 2004 (class I, 28.9%; class
      II, 20.4%; class III, 20.3%). From 1995 through 2004, the percentage of obese
      adults increased from 16.7% to 20.4% in class II and 11.5% to 20.3% in class III
      (P < .001), and the mean BMI increased from 32.1 kg/m2 to 34.4 kg/m2. The
      increase in BMI was greater in the younger age groups. Adjusted mean BMI
      increased significantly over 10 years for each of three treatment categories.
      CONCLUSION: Extreme degrees of obesity are a common and increasing problem among
      AI/AN adults with diabetes. We did not find an association between the type of
      diabetes treatment and the trend toward extreme degrees of obesity. The increase
      in extreme obesity could potentially affect the burden of morbidity and mortality
      among AI/AN adults with diabetes. Effective and culturally appropriate weight
      management interventions are needed.

PMID- 17173715
TI  - Modifiable risk factors for developing diabetes among women with previous
      gestational diabetes.
AB  - INTRODUCTION: Gestational diabetes mellitus (GDM) affects approximately 2% to 4%
      of all pregnant women in the United States each year. Women who have had GDM are
      at high risk for developing nongestational diabetes. The objective of this study
      was to assess the prevalence of modifiable risk factors for developing diabetes
      among women with previous GDM only. METHODS: Cross-sectional data for nonpregnant
      women from the 2003 Behavioral Risk Factor Surveillance System were used to
      estimate and compare the prevalence of modifiable risk factors among three
      groups: nonpregnant women with previous GDM only, nonpregnant women with current
      diabetes, and nonpregnant women without diabetes. RESULTS: In 2003, 7.6% of
      nonpregnant women aged 18 years and older in the United States had current self
      reported physician-diagnosed diabetes, and 1.5% had previous GDM only. Compared
      with women without diabetes, women with previous GDM only had higher prevalence
      of no leisure-time physical activity (32.0% vs 25.7%), overweight (62.2% vs
      49.0%), and obesity (29.4% vs 20.0%). After adjusting for sociodemographic
      variables, women with previous GDM only were more likely to have no leisure-time
      physical activity (prevalence odds ratio [POR], 1.4; 95% confidence interval
      [CI], 1.2-1.7) and more likely to be overweight (POR, 1.8; 95% CI, 1.6-2.2) or
      obese (POR, 1.7; 95% CI, 1.4-2.1), compared with women with no diabetes.
      CONCLUSION: Women with previous GDM are more likely to have modifiable risk
      factors for developing diabetes than women without diabetes. More attention to
      this issue is needed from health care providers and public health officials to
      encourage the promotion of healthy lifestyles during and after pregnancy.

PMID- 17173716
TI  - Efficacy of an emergency department-based motivational teenage smoking
      intervention.
AB  - INTRODUCTION: Motivational interviewing techniques have been minimally researched
      as a function of a teenage smoking intervention. The present study examined the
      efficacy of a theory-based motivational tobacco intervention (MTI). METHODS: A
      randomized two-group design was used to compare 6-month post-baseline quit and
      reduction rates among teenagers who received the MTI with those who received
      brief advice or care as usual. Participants were smokers aged 14 to 19 years (N =
      75) who presented for treatment in a university-affiliated hospital emergency
      department (ED). Motivational interviewing techniques were used by trained
      providers to facilitate individual change; stage-based take-home materials also
      were provided. RESULTS: Similar to past clinic-based studies of motivational
      interviewing with teenage smokers, our study found negative results in terms of
      intervention efficacy for cessation. Six-month follow-up cessation rates were
      nonsignificant--two teenagers quit smoking. Among teenagers who were available at
      follow-up, a medium effect size (Cohen's h = .38) was found for reduction and a
      large effect size (Cohen's h = .69) was found for percentage reduction, although
      these results also were not statistically significant. CONCLUSION: Although the
      major findings of this study were not significant, the reductions in tobacco use
      suggest that motivational interviewing may be a clinically relevant counseling
      model for use in teenage smoking interventions. However, many questions remain,
      and the current literature lacks studies on trials with significant outcomes
      using motivational interviewing in smoking cessation. Additionally, more research
      is needed to examine the suitability of the ED for MTI-type interventions.

PMID- 17173717
TI  - Healthy lifestyle behaviors among older U.S. adults with and without
      disabilities, Behavioral Risk Factor Surveillance System, 2003.
AB  - INTRODUCTION: Little is known about the relationship between healthy behaviors
      and the prevalence of chronic diseases in older adults with disabilities. This
      study examines the prevalence of selected healthy lifestyle behaviors related to
      chronic diseases among adults aged 65 years and older with and without
      disabilities. METHODS: Data from the 2003 Behavioral Risk Factor Surveillance
      System (BRFSS) were used to assess having a healthy weight and six behaviors:
      current cigarette smoking status, consumption of at least one alcoholic beverage
      daily, consumption of at least five fruits or vegetables daily, physical activity
      during the average week, influenza immunization in the past year, and lifetime
      pneumococcal immunization. RESULTS: People with a disability were less likely
      than people without a disability to have a healthy weight (28.5% vs 37.2%) and to
      engage in the recommended level of weekly physical activity (14.7% vs 26.2%).
      However, people with a disability were more likely than those without a
      disability to be nonsmokers (91.8% vs 89.9%), to consume up to one alcoholic
      beverage daily (95.1% vs 91.5%), to have received their influenza immunization in
      the past year (72.7% vs 69.0%), and to have received a lifetime pneumococcal
      immunization (72.1% vs 63.0%). There was no difference between people with and
      without a disability in the prevalence rates of consuming at least five fruits or
      vegetables daily. CONCLUSION: The prevalence of having a healthy weight and six
      chronic-disease related behaviors among adults aged 65 years and older varies by
      disability status and by specific modifiable lifestyle behavior. Screening older
      adults with and without disabilities and counseling them about health behaviors
      should be integrated into every interaction between older adults and their health
      care providers to potentially lower the rates of morbidity and mortality related
      to chronic diseases in the later years.

PMID- 17173719
TI  - The costs of an outreach intervention for low-income women with abnormal Pap
      smears.
AB  - INTRODUCTION: Follow-up among women who have had an abnormal Papanicolaou (Pap)
      smear is often poor in public hospitals that serve women at increased risk for
      cervical cancer. This randomized controlled trial evaluated and compared the
      total cost and cost per follow-up of a tailored outreach intervention plus usual
      care with the total cost and cost per follow-up of usual care alone. METHODS:
      Women with an abnormal Pap smear (n = 348) receiving care at Alameda County
      Medical Center (Alameda County, California) were randomized to intervention or
      usual care. The intervention used trained community health advisors to complement
      the clinic's protocol for usual care. We assessed the costs of the intervention
      and the cost per follow-up within 6 months of the abnormal Pap smear test result.
      RESULTS: The intervention increased the rate of 6-month follow-up by 29
      percentage points, and the incremental cost per follow-up was 959 dollars (2005
      dollars). The cost per follow-up varied by the severity of the abnormality. The
      cost per follow-up for the most severe abnormality (high-grade squamous
      intraepithelial lesion) was 681 dollars, while the cost per follow-up for less
      severe abnormalities was higher. CONCLUSION: In a health care system in which
      many women fail to get follow-up care for an abnormal Pap smear, outreach workers
      were more effective than usual care (mail or telephone reminders) at increasing
      follow-up rates. The results suggest that outreach workers should manage their
      effort based on the degree of abnormality; most effort should be placed on women
      with the most severe abnormality (high-grade squamous intraepithelial lesion).

PMID- 17173718
TI  - Factors associated with overweight and obesity among Mexican Americans and
      Central Americans: results from the 2001 California Health Interview Survey.
AB  - INTRODUCTION: Hispanics are the fastest growing demographic group in the United
      States; however, "Hispanic" is a broad term that describes people who are from or
      whose ancestors are from multiple countries of origin. This study examines,
      separately, the social, cultural, and behavioral factors associated with
      overweight and obesity among Mexican American adults and among Central American
      adults. METHODS: To estimate the prevalence of overweight and obesity among
      Mexican and Central Americans living in California, we conducted a cross
      sectional analysis of data from the 2001 California Health Interview Survey using
      SUDAAN software to account for the survey's multistage sampling design. RESULTS:
      Of the 8304 Mexican Americans participating in the survey, 36.8% were overweight
      and 26.2% were obese. Of the 1019 Central Americans, 39.2% were overweight and
      22.2% were obese. Among Mexican American men, age and marital status were
      associated with overweight and obesity; and education, acculturation, health
      insurance status, health status, and use of vitamins were associated with obesity
      only. Among Mexican American women, age, education, number of children, health
      status, and health behavior were associated with overweight and obesity. Among
      Central American men, age, education, and access to health care were associated
      with overweight, whereas marital status, acculturation, health care, and binge
      drinking were associated with obesity. Among Central American women, number of
      children was associated with overweight and obesity; and age and education were
      associated with obesity only. CONCLUSION: Our findings of high rates of
      overweight and obesity among Mexican and Central Americans in California indicate
      the need for a wide variety of effective weight-loss interventions targeting
      these populations, and the differences we found in the factors associated with
      overweight and obesity may suggest the need for unique intervention strategies
      for different Hispanic subgroups.

PMID- 17173721
TI  - State diabetes prevention and control program participation in the Health
      Disparities Collaborative: evaluating the first 5 years.
AB  - BACKGROUND: Approximately 20.8 million people in the United States, or 7% of the
      population, have diabetes mellitus. Treatment for this disease costs Americans
      more than 130 billion dollars yearly, and it is the sixth leading cause of death.
      The prevalence of diabetes has grown substantially in recent decades and is
      expected to continue to rise. CONTEXT: The medically underserved and poor are at
      greater risk of developing diabetes and its complications than are other members
      of the U.S. population. The Health Resources and Services Administration makes
      health care resources and services available to economically disadvantaged
      populations through the Health Disparities Collaborative (HDC), a consortium
      formed to pool resources and services from state- and community-level donors.
      Since 1999, many of the Centers for Disease Control and Prevention's Division of
      Diabetes Translation State Diabetes Prevention and Control Programs (DPCPs) have
      joined the HDC to leverage resources and services. METHODS: The purpose of a 2004
      evaluation was to examine the impact that DPCP involvement with the Collaborative
      had on aspects of diabetes care at Federally Qualified Health Centers (FQHCs). An
      electronic survey was administered to DPCP coordinators. They were asked about 1)
      their roles and experience as participants in the Collaborative; 2) the skills
      and expertise most useful in developing and maintaining an effective
      collaboration for improved health care for diabetes; 3) which DPCP contributions
      were viewed as being routine and which were perceived to be essential; 4) the
      effects of DPCP contributions on the use of the chronic care model under which
      FQHCs operate; and 5) which health systems improvements played the greatest role
      in enhancing components of the chronic care model. CONSEQUENCES: Most respondents
      identified themselves as DPCP coordinators with 3 years of experience in that
      position. Organizational skills, such as communication, leadership, conflict
      resolution, negotiation, and meeting management, were cited as necessary to
      develop and maintain collaborative partnerships. DPCP contributions to FQHCs were
      perceived to be training, technical assistance with clinical care and patient
      education, financial resources, linkages to other diabetes partners, educational
      materials, and improved linkages with community resources. INTERPRETATION: DPCPs
      contribute resources, skills, knowledge, and varied perspectives to the
      Collaborative that FQHCs may not have otherwise.

PMID- 17173720
TI  - The healthy diabetes plate.
AB  - BACKGROUND: Diabetes education presents two major challenges to the U.S.
      Cooperative Extension System. The first is that the majority of diabetes
      education services are provided in more populated areas, resulting in large
      nonurban areas being underserved. The second is that many individuals with
      diabetes find the meal-planning component of diabetes education confusing.
      CONTEXT: The University of Idaho, a land-grant institution, includes teaching,
      research, and extension as part of its mission. Extension means "reaching out,"
      and in Idaho, the Extension Service provides research-based programs on
      agricultural, natural resources, youth, family, community, and environmental
      issues in 42 of Idaho's 44 counties, making it accessible to most Idahoans.
      METHODS: The University of Idaho Extension Service collaborated with dietitians
      and certified diabetes educators to develop and test materials that simplify the
      meal-planning component of diabetes education. The result was a four-lesson
      curriculum, The Healthy Diabetes Plate, which used the plate format to teach
      individuals about the type and amount of foods they should consume at each meal.
      In 2004, the four-lesson curriculum was taught in three urban and five rural
      counties. Surveys, hands-on activities, and note-taking of participants' comments
      were used to collect data on participants' characteristics, their ability to plan
      meals, and changes in eating habits. CONSEQUENCES: Participants were able to
      correctly plan breakfast, lunch, and dinner meals and improved their intake of
      fruit and vegetables. INTERPRETATION: Quantitative and qualitative evaluation
      information gathered from class participants helped identify which components of
      The Healthy Diabetes Plate curriculum were effective.

PMID- 17173722
TI  - What does the population attributable fraction mean?
AB  - Recent controversy over the disagreement of population attributable fraction
      estimates for the obesity-total mortality relation has made the concept of
      attributable fraction visible in both scientific and popular news. Most of the
      attention in writings on the attributable fraction has focused on technical
      matters of estimation and on ensuring a causal relationship between exposure and
      outcome. Yet some of the most illuminating questions about the attributable
      fraction have to do with another causal question and how the measure is to be
      interpreted in light of the answer to this question: What interventions are
      available to cause the assumed reduction in risk among the exposed and the
      consequent estimated reduction in disease burden? In this paper, I discuss the
      limitations to the common interpretations of the attributable fraction and argue
      that these limitations cannot be overcome merely by better statistical modeling
      or by use of better data sets. They must be addressed through discussion of
      specific interventions and the hypothesized causal consequences of such specified
      interventions.

PMID- 17173723
TI  - Local health departments and the challenge of chronic disease: lessons from
      California.
AB  - The essential role local health departments have played in the control of
      infectious diseases has not been matched with an equivalent contribution in
      prevention of chronic diseases. Local health departments have attempted to define
      and build that capacity, but they have been confronted with budget cuts and
      competing public health priorities, most notably bioterrorism preparedness. This
      article is based on interviews with local health officials and describes some of
      the common ways local health departments in California have forged ahead to
      develop the capacity to engage in comprehensive approaches to chronic disease
      prevention in spite of the challenges. Additionally, the article highlights
      future considerations that need to be addressed if these promising trends in
      chronic disease prevention are to become more widespread.

PMID- 17173724
TI  - Building community capacity for health promotion in a Hispanic community.

PMID- 17173726
TI  - Public health attention for physical activity.

PMID- 17173727
TI  - Paradigms lost?
AB  - Thomas Kuhn (1957, 1962) explored the issues of paradigm shifts, scientific
      revolutions, and the relationship between them. Written before the techniques and
      practices of the complexity sciences were developed, Kuhn described what he
      termed the Copernican Revolution as the last scientific revolution signifying a
      paradigmatic shift in society. We will explore whether New Science approaches in
      nonlinear dynamics and complexity research signify postmodern science
      perspectives, and examine the role of New Science in what may be the on-going
      evolution of the next paradigm shift.

PMID- 17173728
TI  - Complexity: the co-evolution of epistemology, axiology and ontology.
AB  - If epistemology is about what we know and how we know what we know (what is
      inside) and ontology is about what there is to know (what is outside) then the
      most fundamental challenge that complexity makes is that these can no longer be
      considered as separable. Traditional science was based on the idea that there was
      an objective reality outside, and that we could study it and do experiments on it
      that allowed us to build, cumulatively, an increasingly accurate picture of that
      reality. Whilst for simple physical problems, and for planetary motion, this was
      a reasonable working hypothesis, for biological and social systems this has
      always been a problem. Experiments are not repeatable or transferable, and
      situations are historically evolved involving local, co-evolving contexts, and
      therefore can potentially all be unique and lacking in any generic behaviours or
      laws. Complexity science brings us face to face with this elusive reality, and
      tells us that we must accept uncertainty, and admit that our cognition, our
      descriptions and our models are necessarily incomplete and temporary props to our
      current functioning. They help us make some sense of the past and the present,
      and are all we have to help us in taking steps into the future. Examples of these
      ideas will be given for ecological, social and economic systems, showing that
      models, despite their necessary incompleteness, can still be useful in clarifying
      and living with some of the real uncertainties we have, and in this way can help
      us explore possible futures. However, complexity also tells us that we need not
      limit our explorations to those suggested by our models, since they are
      necessarily incomplete, and that we should also indulge in "creative actions" in
      order to find out more about what might happen, and in this way both increase our
      possible choices of action, and also improve the scope of our models.

PMID- 17173729
TI  - Complexity and cognition: a meta-theoretical analysis of the mind and brain as a
      topological dynamical system.
AB  - The application of theories of complexity to the study of cognition has only
      recently started but it has already caused high expectations and controversies.
      Currently an extensive evaluation of the theoretical status of these theories
      does not exist. In an attempt to fill in that gap, this text develops a meta
      theoretical analysis that presents a reconstruction of the theories of complexity
      applied to cognition, establishing their theoretical status, conceptual cores,
      basic assumptions and explanation strategies. Freeman's theory of cerebral chaos
      will be analyzed first. Then a meta-theory generalization to neuro-cognitive
      theories will be presented. It will be sustained that the central theoretical
      core of cognitive complexity theories are based on the metaphor of the mind, the
      brain or cognition as a dynamic system, founded a time-space topology. The
      framework of this study is based on ontology of processes and an ontological
      pluralism. The explicative strategies are supported by emergentistic approaches
      and nomological derivation based on mathematical laws. The prototypes of the
      theory are strongly backed up by computer simulations. This paper concludes by
      suggesting the existence of two antagonical perspectives (universalistic and
      pluralistic) in the core of these theories.

PMID- 17173730
TI  - The emergence of leadership in coordination-intensive groups.
AB  - Although group coordination was introduced to psychology in the early 1990s, it
      was not until the advent of nonlinear dynamical systems (NDS) that it was
      possible to gain an understanding of how the process of implicit learning and
      self-organization take place in conditions where no hierarchical (management)
      influences are involved. This experimental study examined how leaders might
      emerge from coordination-intensive task groups where verbal interaction is not
      possible. NDS and game-theoretical research indicate that the presence of leaders
      is not required to produce coordination. Thus the question remains as to whether
      leaders would emerge from coordination-intensive task groups in the similar
      manner to how they emerge from other types of groups. In the experiment, 13 4
      person groups were allowed to discuss the coordination (card game) task while
      performing it; 13 other groups worked nonverbally. Split-plot ANOVA showed that
      verbalizing groups performed better than nonverbalizing groups overall and showed
      more acute coordination learning curves. Nonlinear regression for temporal
      dynamics within verbalizing and nonverbalizing groups showed asymptotic stability
      for initial coordination learning and transfer to a coordination rule of equal
      difficulty, but a chaotic function was observed when the teams switched to a more
      difficult coordination rule. A questionnaire measured leadership emergence at the
      end of the game along with other social contributions to the groups' efforts. The
      average level of leadership emergence for individuals did not differ between
      verbal and nonverbal conditions, although differences in other social
      contributions were observed. This experiment illustrates, furthermore, how the
      nonlinear science paradigm produces new hypotheses concerning verbalization that
      would not have been formulated otherwise. New avenues of study concerning
      coordination, leadership, and hierarchies are also discussed.

PMID- 17173731
TI  - Do nonlinear dynamics in economics amount to a Kuhnian paradigm shift?
AB  - Much empirical analysis and econometric work recognizes that there are
      nonlinearities, regime shifts or structural breaks, asymmetric adjustment costs,
      irreversibilities and lagged dependencies. Hence, empirical work has already
      transcended neoclassical economics. Some progress has also been made in modeling
      endogenously generated cyclical growth and fluctuations. All this is inconsistent
      with neoclassical general equilibrium. Hence there is growing evidence of Kuhnian
      anomalies. It therefore follows that there is a Kuhnian crisis in economics and
      further research in nonlinear dynamics and complexity can only increase the
      Kuhnian anomalies. This crisis can only deepen. However, there is an ideological
      commitment to general equilibrium that justifies "free enterprise" with only
      minimal state intervention that may still sustain neoclassical economics despite
      the growing evidence of Kuhnian anomalies. Thus, orthodox textbook theory
      continues to ignore this fact and static neoclassical theory remains a dogma with
      no apparent reformulation to replace it.

PMID- 17173733
TI  - Commentary on paradigms and key word index for NDPLS articles 1997-2006.
AB  - Although a paradigm shift in the sense of a postmodern worldview might be taking
      shape in society at large, the core concepts of nonlinear science date back a
      century, and are only tangentially influenced by other intellectual developments.
      Relative to contemporary science it offers new concepts concerning events that
      transpire over time, new hypotheses, new methods for answering new questions,
      some efficient answers, and a new perspective for understanding what we do not
      know in addition to knowing how we know what we know. Paradoxically, nonlinear
      science can be viewed as a narrow specialty within a specific discipline and as a
      general systems theory that identifies common themes that underlie phenomena
      found in a wide range of disciplines and specialties. The key word index
      illustrates the breadth of concepts and applications found in NDPLS, and some
      pathways for continued growth of the field.

PMID- 17173732
TI  - Process and meaning: nonlinear dynamics and psychology in visual art.
AB  - Creating and viewing visual art are both nonlinear experiences. Creating a work
      of art is an irreversible process involving increasing levels of complexity and
      unpredictable events. Viewing art is also creative with collective responses
      forming autopoietic structures that shape cultural history. Artists work largely
      from the chaos of the unconscious and visual art contains elements of chaos.
      Works of art by the author are discussed in reference to nonlinear dynamics.
      "Travelogues" demonstrates continued emerging interpretations and a deterministic
      chaos. "Advice to the Imperfect" signifies the resolution of paradox in the
      nonlinear tension of opposites. "Quanah" shows the nonlinear tension of opposites
      as an ongoing personal evolution. "The Mother of All Things" depicts seemingly
      separate phenomena arising from undifferentiated chaos. "Memories" refers to
      emotional fixations as limit cycles. "Compassionate Heart," "Wind on the Lake,"
      and "Le Mal du Pays" are a series of works in fractal format focusing on the
      archetype of the mother and child. "Sameness, Depth of Mystery" addresses the
      illusion of hierarchy and the dynamics of symbols. In "Chasadim" the origin of
      worlds and the regeneration of individuals emerge through chaos. References to
      chaos in visual art mirror the nonlinear complexity of life.

PMID- 17173734
TI  - [Vision quality of intraocular refraction surgery].
AB  - Intraocular refractive surgery is one of challenges since it is undertaken mostly
      for high myopia patient with healthy transparent crystalline lens. The improved
      vision quality is the premise for conducting this kind of surgery. Vision quality
      is one of comprehensive factors which are connected to the surgery techniques,
      ocular optics, ocular physical biometry, intraocular lens power calculation and
      psycho-physical perception of patient.

PMID- 17173735
TI  - [Influence of diameter of optical zone ablation on LASIK-induced higher order
      optical aberrations in myopia].
AB  - OBJECTIVE: To analyze the effects of optical zone ablation diameter on LASIK
      induced higher order optical aberrations in myopia. METHODS: Four hundred and
      sixty-one eyes of 236 patients treated with LASIK for myopia were divided into
      high, moderate and low myopia group according to preoperative spherical
      equivalent diopter. In each group, eyes were divided into four subgroups
      according to optic zone ablation diameter. Before and after surgery 6 months,
      monochromatic wavefront aberrations of each eye were objectively measured using
      WASCA Analyzer Aberrometer. F test and q test were used to analyze the difference
      of total high order, horizontal coma, vertical coma, and spherical aberrations
      among four subgroups in each group at 4, 5, and 6 mm pupil size. RESULTS: Before
      surgery no significant difference of higher order aberrations among four
      subgroups was found. After surgery, there was significant difference of total
      high order, and spherical aberrations among four subgroups. Total high order, and
      spherical aberrations in larger optical zone ablation diameter subgroup were
      significantly lower than that in smaller one. The difference was significant at
      4, 5, and 6 mm pupil size in high myopia group, and 6 mm pupil size in low myopia
      group. At 6 mm pupil size, the difference was significant between each subgroup
      in high myopia group and subgroup I and subgroup IV in low myopia group. There
      was no significant difference of horizontal coma, and vertical coma aberrations
      among four subgroups. CONCLUSIONS: Optical zone ablation diameter has influence
      on LASIK-induced higher order optical aberrations. Larger optical zone can
      decrease total higher order and spherical aberrations after LASIK. The effects
      are more significant in high myopia group than in low myopia group.

PMID- 17173736
TI  - [Analysis of the dynamic changes of cornea after myopic excimer laser in situ
      keratomileusis using an Orbscan II topography system].
AB  - OBJECTIVE: To study the changes and influence factors of an Orbscan II topography
      system in myopia after excimer laser in situ keratomileusis (LASIK). METHODS: Two
      hundred and sixteen myopia patients (230 eyes) were treated by LASIK, their
      corneal thickness and curve of corneal posterior surface was measured with an
      Orbscan II topography system before and after surgery. The results of measurement
      in different time points were compared. RESULTS: The thinnest point of cornea,
      the mean keratometry of the posterior best fit surface (BFS) and the distance
      from the apex to the BFS were significant difference before and after operation
      (P < 0.05). There were significant difference among those groups in different
      degree of myopia in the same time point (P < 0.05) after surgery, but there were
      no significant difference in the same group in difference time (P > 0.05). A
      significant difference in the area of the thinnest cornea before surgery and
      after surgery was detected among those groups (P < 0.01). The regression equation
      for preoperative Diff value was established as Y = 0.0941 - 0.000,53X(1) -
      0.000,471X(2) - 0.0063X(3) + 0.001,22X(4) (P < 0.01), X(1) = corneal thickness of
      the thinnest point (microm), X(2) = central corneal thickness (microm), X(3) =
      corneal diameter (mm), X(4) = length of ocular axis (mm). The regression equation
      for postoperative decrease Diff value between the third month and the first month
      was produced as Y = - 0.027 - 0.000,78X(1) + 0.002,01X(2) - 0.0055X(3) (P <
      0.01). X(1) = decrease in corneal thickness of the thinnest point (microm), X(2)
      = intraocular pressure pre-surgery (mmHg), X(3) = decrease in curvature of
      posterior corneal surface (D). CONCLUSIONS: The application of Orbscan II has an
      important clinical significance before and after LASIK. The Diff value measured
      before LASIK for myopia is influenced by the corneal thickness, corneal diameter
      and ocular axis. The postoperative decrease in Diff value between the third and
      first month is influenced by the postoperative decrease of corneal thinnest point
      and curvature of posterior corneal surface, and preoperative intraocular
      pressure.

PMID- 17173737
TI  - [The relationship between corneal astigmatism with a vector-based method and
      whole eye second order wavefront aberrations].
AB  - OBJECTIVE: To investigate the relationship between corneal astigmatism and second
      order wavefront aberration in myopic eyes. METHODS: The corneal astigmatism and
      the whole eye wavefront aberrations of both eyes of 246 subjects were measured
      using the Humphrey corneal topography and the WASCA wavefront analyzer. According
      to axial of the corneal astigmatism, the subjects were divided into five groups
      (WR(0), WR(180), AR, OA(45) and OA(135)). The corneal astigmatism was decomposed
      into J(45) and J(0) with a Vector-based method, and correlated with the 2nd order
      Zernike aberrations (C(3) and C(5)). RESULTS: The mean corneal astigmatisms for
      the five groups were -1.34 D x 6.87 degrees, -1.03 D x 23.15 degrees, -0.48 D x
      89.55 degrees, -0.91 D x 156.87 degrees and -1.02 D x 176.74 degrees
      respectively. Most of the corneal J(45) and J(0) components were correlated
      significantly with the C(3) and the C(5) aberrations in the whole eye. While the
      correlation coefficients (R(2)) between the J(45) and the C(3) were 0.138, 0.119,
      0.090, 0.526 and 0.501, the R(2) between the J(0) and the C(5) were 0.711, 0.736,
      0.864, 0.866 and 0.785 for the five groups respectively. CONCLUSIONS: The corneal
      astigmatism plays an important role in determining the 2nd order wavefront
      aberration in the whole eye, and the combination processes between the corneal
      and internal astigmatism (compensation and/or addition) change with the axial of
      the corneal astigmatism.

PMID- 17173738
TI  - [The grating acuity of children in preschool age].
AB  - OBJECTIVE: To study the developmental trend of the binocular grating acuity of
      preschool children. METHODS: Binocular grating acuities in 599 children from 2
      months to 72 months old (18 groups) were measured using the closed-circuit
      operant preferential looking system (COPLs). The children included in the
      investigation were required to be a normal term birth, development and normal
      eyes, and cycloplegic refraction error within specific limits. The system's
      reliabilities and measurable rates were also evaluated. RESULTS: The difference
      of the vision acuities obtained by the same tester on different days has no
      statistic significance. The measurable rates reached 90% in most age groups. The
      grating acuity of the children included in the study developed rapidly during
      first year, and then it reached to a slower development period from 30 to 36
      months, the grating acuity stabilized after 3 years old. CONCLUSION: The COPL
      system is a practical devise to assess the grating visual acuity of infants and
      preschool children and it can be used to investigate the vision developmental
      trend including speed, age of its maturation and the top-acuity of the
      development.

PMID- 17173739
TI  - [The roles of AC/A ratio and other ocular motor parameters in the induction of
      late-onset myopia].
AB  - OBJECTIVE: This study was to explore ocular motor parameters (accommodation and
      convergence) in late myopia onset and development. METHODS: Eleven Emm
      (emmetrope), 14 S.M. (stable late-onset myopia), and 9 P.M. (progressing late
      onset myopia) were include in this study. Phoria at distance and near, positive
      and negative relative accommodation (NRA/PRA), accommodative convergence and
      accommodation response were measured. RESULTS: Response AC/A ratio of P.M. was
      higher than that of Emm or S.M. (P < 0.05); But statistically AC/A ratio was not
      significant difference (P > 0.05). Accommodation response (3.00 D) of Emm was
      higher than P.M and S.M (P < 0.05). There was significant difference in phoria in
      near between LOM and Emm, but none in that of distance. There was no significant
      difference in NRA. However, PRA of LOM was lower than that of the Emm (P < 0.05).
      CONCLUSIONS: Ocular motor parameters are important in LOM onset and development.
      Response AC/A ratio (not calculated AC/A ratio) is one of key parameters among
      them, Response AC/A ratio is the highest in P.M, which indicates out of focus of
      retinal image in the developing LOM.

PMID- 17173740
TI  - [Stromal cells change after epipolis laser in situ keratomileusis and laser
      assisted subepithelial keratectomy in rabbits].
AB  - OBJECTIVE: To compare the effects of epipolis laser in situ keratomileusis (Epi
      LASIK) and laser-assisted subepithelial keratectomy (LASEK) on the corneal
      stromal cells, and to evaluate their effects on corneal haze histopathologically.
      METHODS: Forty-eight New Zealand white rabbits (96 eyes) were randomly treated
      with Epi-LASIK in one eye and LASEK in the other, and 2 rabbits (4 eyes) without
      any treatment were used as control. Cornea stromal cell apoptosis was evaluated
      by terminal deoxyribonucleotidyl transferase-mediated deoxynuridine triphosphate
      nick end labeling (TUNEL) assay. Stromal cells proliferation and myofibroblasts
      generation were evaluated by immunocytochemical analyses the expression of Ki-67
      and alpha-smooth muscle actin (alpha-SMA) respectively. Myofibroblast generation
      was further testified by Western blot analysis of alpha-SMA. Both number of
      TUNEL, Ki-67 and alpha-SMA positive cells and expression of alpha-SMA were semi
      quantitatively analyzed to explore their effects on corneal haze. RESULTS: Many
      TUNEL-positive cells appeared in the central anterior stromal in early stages
      after both LASEK and Epi-LASIK, and the number of TUNEL-positive cells reached a
      peak 24 hours after either LASEK or Epi-LASIK. There were more TUNEL positive
      cells found in LASEK group than that in Epi-LASIK group in 1 week postoperatively
      (t = 3.63, 7.80, 4.34, 2.95, all P < 0.01). There were a lot of Ki-67-positive
      cells in anterior corneal stroma after both LASEK and Epi-LASIK, but the peak
      appeared at 72 hours after the treatments. The significant difference was also
      found in the number of Ki-67-positive cell between the two treatments in 1 week
      postoperatively (t = 3.81, 5.85, 5.09, 5.59, all P < 0.01). alpha-SMA-positive
      cells started to appear apparently at 1 week after both LASEK and Epi-LASIK, and
      both the peaks appeared at 1 month after the treatments, and there were still a
      lot of alpha-SMA-positive cells in corneal stroma at 3 months after LASEK. There
      were more alpha-SMA-positive cells found after 1 week in LASEK group than that in
      Epi-LASIK group (t = 2.97, 7.19, 6.73, all P < 0.01). CONCLUSION: There are less
      stromal cell apoptosis, proliferation and myofibroblast generation in Epi-LASIK
      than that in LASEK. Therefore, comparing with LASEK, Epi-LASIK induces less
      corneal haze response in correcting myopia.

PMID- 17173741
TI  - [A cross-sectional survey of blindness and low vision among adults aged 60 years
      and above in Xinchengqiao Blocks, Nantong].
AB  - OBJECTIVE: To investigate the prevalence and causes of blindness and low vision
      among adults aged > or = 60 years in the urban population of Nantong. METHODS:
      Cluster sampling was used to select 8 from 14 communities in Xinchengqiao Blocks,
      in which all individuals aged > or = 60 years were visited. The visual acuity
      without correction and the presenting acuity with the participants' habitual
      distance correction were measured separately for each eye. In individuals with
      visual acuity less than 0.6, pinhole visual acuity was tested with pinhole
      spectacle. External eye, anterior segment and ocular fundus were examined by the
      ophthalmologist using a slit lamp-microscope and direct ophthalmoscopy. The
      survey was preceded by a pilot study. RESULTS: Of 3352 enumerated subjects, 3040
      individuals participated in this survey (90.69% response rate). According to
      pinhole visual acuity and World Health Organization (WHO) visual impairment
      criterion (blindness: less than 0.05 in the better eye; low vision: less than 0.3
      to 0.05 in the better eye), the prevalence of blindness and low vision was 1.35%
      and 1.84% respectively. The prevalence of blindness and low vision for females
      were 1.92% and 2.33%, respectively, which were differenced from that in males
      (0.66% and 1.24%, respectively). The prevalence of blindness and low vision
      increased with age. The survey showed that the most important cause leading to
      blindness and low vision was cataract. According to the presenting visual acuity
      and visual impairment criterion (blindness: less than 0.1 in both eyes), the
      prevalence of blindness and visual impairment was 1.58% and 13.59%, respectively,
      2.10% and 15.98% in females and 0.95% and 10.66% in males, respectively. The
      prevalence of blindness and visual impairment was raised with increasing age.
      Cataract was also the leading cause for blindness. CONCLUSIONS: The prevalence of
      blindness in the Nantong area was lower than that in northern, southern and
      western China. Females and illiteracy were more likely to have blindness and low
      vision than that of males and literate. The leading causes of blindness in
      Nantong are, in descending sequence, cataract, ocular fundus diseases, ametropia
      and corneal scar/opacity.

PMID- 17173742
TI  - [Experimental study on corneal organ culture preservation and its application].
AB  - OBJECTIVE: To develop a optimal method of corneal organ culture preservation, to
      evaluate the characteristics of organ cultured cornea and to examine the
      feasibility of application of organ cultured corneas. METHODS: Thirty-six adult
      New Zealand rabbit corneas were stored in the closed storage system consisting of
      fetal calf serum and were transferred to a hyperosmosis dextran-containing medium
      for 48 hours' deswelling for further experiment after storage for 1, 2, 3 and 4
      weeks. The measurement of corneal endothelium density and central thickness was
      performed prior to and after the storage. The morphology and the contamination of
      preserved cornea, as well as allogenic grafts' conditions within 7 days after
      corneal transplantation were also observed. The class II MHC antigen
      immunofluorescence marker was performed for the examination of corneal dendritic
      cells by confocal microscopy. RESULTS: The corneal organ culture preservation was
      successfully established. The contamination rate was approximately 8.3%. All of
      the rabbit corneas stored within 4 weeks remained transparent. There were little
      folds in peripheral descemet's membrane when the storage time was up to 3 weeks
      and the whole descemet's membrane folds was seen when the corneas had been
      preserved for 4 weeks. The density of corneal endothelium decreased when the
      preservation time was extended. The loss of corneal endothelium preserved up to 4
      weeks was 15.7%. Correlation existed between the thickness of center cornea and
      the preservation time. The average central thickness of the cornea was 0.7 mm
      after 4 weeks. The light micrographs showed that the endothelium layer still
      covered the descemet's membrane completely after 4 weeks. The dendritic cells
      resided in the limbus epithelium and they were lost after stored for 3 weeks.
      After allogenic corneal transplantation, the grafts retained transparency within
      7 days postoperatively, which indicated that there was no primary failure of
      grafts. CONCLUSION: Corneal organ culture preservation can ensure the normal
      function of cultured cornea within a certain preservation time and offer some
      advantages, e.g. the decrease of corneal immunogenicity.

PMID- 17173743
TI  - [The dynamic study of retinoic acid and its alginate sodium microspheres in
      rabbit eye].
AB  - OBJECTIVE: To obtain a intravitreous delay release system by injection of
      biodegradable polymers (alginate sodium-retinoic acid microspheres, AGS-RA
      microspheres) to the rabbit vitreous and study the release character of RA
      delivery system in vitro. METHODS: RA was mixed with 1.5% alginate sodium and
      microspheres was made by a special electrostatic generator after dissolved in
      organic solvent; The content of AGS-RA in the microspheres and its release from
      the microspheres were measured by spectrophotometer. The characteristic of the
      metabolic dynamics of AGS-RA in the microspheres was analyzed by HPLC. RESULTS:
      The size of microspheres we manufacture is (95.2443 +/- 8.6265) microm; Medicine
      contain quantity of RA is (1.7644 +/- 0.0453) microg/mg; Vitro test show that RA
      in the microspheres is release evenly in the 28 days of observation; Inject
      medicine to vitreous cavity show no poisonous side effect; The medicine dynamics
      research of microspheres showed that medicine is being even in 6 weeks releasing
      [the aqueous RA density of 1, 3 d, 1, 2, 3, 4, 5, 6 weeks is (23.79 +/- 0.15),
      (33.45 +/- 0.48), (19.95 +/- 0.79), (21.12 +/- 0.47), (19.65 +/- 0.35), (20.01 +/
      0.25), (18.24 +/- 0.27), (18.5 +/- 0.68) ng/ml, respectively]. Just in the 3rd
      day there is a release summit. CONCLUSION: In vivo and in vitro tests show that
      AGS-RA microspheres can delay RA release uniformity.

PMID- 17173744
TI  - [The effects of hematopoietic stem cells on mice vascular endothelial cells of
      diabetic retinopathy].
AB  - OBJECTIVE: The purpose of the study was to determine whether hematopoietic stem
      cell (HSCs) mobilization can regulate early diabetic retinopathy in mice.
      METHODS: Mice were divided into four groups: control group, normal mice HSC
      mobilized group, diabetic mice control group and diabetic mice HSC-mobilized
      group. Murine stem cell growth factor (SCF) and recombined human granulocyte
      colony stimulating factor (rhG-csf) were administered to the mice with diabetes
      and without diabetes for continuous 5 days to induce autologous HSCs
      mobilization, and subcutaneous injection of physiological saline was used as
      control. The changes associated with autologous HSCs mobilization were
      characterized using flow cytometry, Immunohistochemistry and semiquantitative RT
      PCR. Evans blue quantitative test was used to measure the breakdown level of
      blood-retina barrier. RESULTS: HSCs were marked by CD34-/low and Sca1+ in this
      study. The acceleration of endothelial cell regeneration was observed. A decrease
      of VEGF expression due to autologous stem cell mobilization was found. HSCs could
      increase the content of VEGFR-2 in mouse retina and significantly downregulated
      the expression of VEGF and ang-2 in diabetic mice. CONCLUSIONS: The experiment
      suggest that autologous HSCs mobilization can be approach of therapeutic vascular
      reconstruction and functional restoration of blood-retina barrier in mice.

PMID- 17173745
TI  - [Inhibitory effect of RGDS peptide on experimental choroidal neovascularization
      in a rat model].
AB  - OBJECTIVE: To investigate the efficacy and feasibility of RGDS (Arg-Gly-Asp-Ser)
      peptide (an alpha(nu)-integrin antagonist) in a rat model of laser-induced
      choroidal neovascularization (CNV). METHODS: Experimental CNV was induced by
      laser photocoagulation in Brown Norway rats (50 microm diameter, 0.05 second
      duration and 525 mw intensity). Phosphate buffered saline (PBS) or 100, 300
      microg of RGDS peptide in PBS were being injected intravitreally after laser
      surgery for 7 days. On the 14th day after photocoagulation, CNV was observed by
      fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA).
      The area of CNV by high molecular weight FITC-dextran (MW 2 x 10(6)) for high
      resolution angiography in RPE-choroid-sclera flat mounts and the thickness
      microscopically on histologic sections were evaluated. New vessels were detected
      and quantified by an-antibody against factor VIII. Two eyes from each group were
      examined by transmission electron microscopy. RESULTS: In eyes with injections of
      300 or 100 microg of RGDS peptide on the 14th day after laser photocoagulation,
      the development of CNV was significantly (P < 0.01) inhibited showing by RPE
      choroid-sclera flat mounts. Histologically, the thickness of the CNV lesions was
      significantly (P < 0.01) reduced in eyes that received 300 or 100 microg of RGDS
      peptide injection. Immunoreactivity of factor VIII in CNV showed significant
      difference (P < 0.01) in eyes injected with RGDS peptide compared with control
      eyes. The reduction of the area and the thickness of CNV by RGDS peptide were in
      a dose-dependent manner. No evidence of toxicity was found in retina by
      transmission electron microscopy in every group. CONCLUSIONS: RGDS peptide
      effectively inhibits CNV progression in a rat model of laser-induced CNV,
      suggesting that this alpha(nu)-integrin antagonist may be beneficial in the
      treatment of CNV.

PMID- 17173756
TI  - [Progress in the study of ophthalmic molecular biology].
AB  - Abundant progress has been made in the study of molecular biology in the last
      decade, which included the practical application of RNA interference, proteomic,
      molecular image and nano technology. The communication between bioscience with
      other branches (including ophthalmology) enhanced the further development of
      bioscience. This review briefly summarizes these new cutting age information in
      the field of molecular biology related with eye research to help us to acquire a
      deeper understanding of the pathogenesis and mechanism of treatment for systemic
      and eye diseases.

PMID- 17173755
TI  - [Myelin associated inhibitors and regeneration of optic nerve].
AB  - The failure of axonal regeneration after optic nerve injury in mammals is closely
      related to nonpermissive microenvironment in central nervous system as well as to
      the low regenerative ability of retinal ganglion cells. Myelin associated
      inhibitors produced by oligodendrocytes are major elements of this nonpermissive
      microenvironment. Three major inhibitors, Nogo, myelin-associated glycoprotein
      and oligodendrocyte myelin glycoprotein, have been identified, which lead to
      signal inhibition through the same receptor complex. Blocking the inhibitors and
      their receptors or changing the intrinsic state of the neuron to overcome the
      inhibition may promote retinal ganglion cell axonal regeneration after optic
      nerve injury, which bring a hope to solve the problem of repair of injured optic
      nerve.

PMID- 17173757
TI  - [Application of femtosecond laser in corneal refractive surgery].
AB  - The function of photo-decomposing of femtosecond laser makes it useful in
      creating precise "cuts" at arbitrary locations within the corneal of almost any
      conceivable geometry. The applications of femtosecond laser include intrastromal
      photorefractive keratectomy, creating the pre-cut channels for intra-corneal ring
      segment, creating lamellar flaps for laser in situ keratomileusis, performing
      femtosecond lamellar keratoplasty, which represent an entirely new approach for
      the correction of refractive errors.

PMID- 17173758
TI  - [Vitamin C].
AB  - Vitamin C or ascorbic acid is a hydrosoluble vitamin derived from glucose
      metabolism. It acts as a reductor agent required for synthesis of collagen fibers
      through hydroxylation of proline and lysine. It also protects the body against
      damage caused by the free radicals. Humans cannot synthesize ascorbic acid as
      they lack an enzyme called gulonolactone oxidase. Concentrations in plasma and
      leukocytes reflect the levels of the diet and body deposits respectively of this
      vitamin. Among foods with high vitamin C levels are tomatoes, potatoes, and
      citrus fruits such as limes, oranges and lemons. The current recommendation of
      daily intake of vitamin C is 90 mg/d for men and 75 mg/d for women. Patients with
      chronic diseases such as cancer or diabetes or those who smoke need higher doses
      in their usual diet. Ascorbic acid deficiency gives rise to the appearance of
      scurvy. This disease is rarely seen in developed countries. The symptoms develop
      with plasma levels below 0.15 mg/dL. Scurvy is characterized by the presence of
      weakness, joint pain or skin lesions in form of petechias, gum bleeding, ease of
      developing bruises or delay in wound healing. The most characteristic skin
      manifestations are purpuric perifollicular hyperkeratotic papules and the
      presence of kinky hair.

PMID- 17173759
TI  - [Analysis of the reasons for consultation and dermatology care cost in a primary
      care site].
AB  - INTRODUCTION: The objective of the study was to the visits for esthetic reasons
      in an out-patient dermatology consultation and their cost and calculate the
      invoicing of these visits for a site other than the medical specialist consulted.
      METHOD: Prospective study in an out-patient dermatology clinic for 12 random days
      in February 2005. Endpoints of age, gender, diagnosis, cost per visit,
      cryotherapy and electrocoagulation were collected. Patients were divided into 3
      groups: request for esthetic treatment (A), request for dermatology visit (B) and
      did not come (C). RESULTS: Group B was the largest, with 205 users (46 %),
      followed by C with 134/455 (29 %) and by A with 116/455 (25 %). In the latter
      group, the diagnoses were: seborrheic keratosis 39/455 (9 %), acrocordons 21/455
      (5 %), remaining diagnoses (intradermal melanocytic nevi, cherry angioma, solar
      lentigos): 56/116 (11 %). The cost of these visits was 2,528. 8 euros in the 12
      days analyzed and treatment of a subgroup of 85 patients (18.75 %) with
      cryotherapy or electrocoagulation increased it up to 5,043.80 euros. Estimated
      cost for one year would be 82,950 euros. Calculation of the invoicing for a non
      public supplier site to the National Health Service would be: 8769.60 euros/month
      and 97,875 euros/year. If we add the treatments described, we go from 28,403.40
      euros/month to 317,113.80 euros/year. CONCLUSIONS: These data and daily
      experience should make us think about the ethical consequences (do all the
      patients have to wait the same time?) as well as legal and collective ones (what
      type of dermatology do we want to specialize in?).

PMID- 17173760
TI  - [Chondroid syringoma: a clinical and histological review of eight cases].
AB  - INTRODUCTION: Chondroid syringoma is a rare skin tumor that presents as a slow
      growing, indolent lesion, that is more frequent in male adults and is usually
      benign. It is treated surgically and its diagnosis is histological. It can be
      classified as eccrine and apocrine according to its pathological characteristics.
      MATERIAL AND METHODS: Eight cases diagnosed of chondroid syringoma in our
      Department in the last eight years were reevaluated clinically and histologically
      and the epiluminiscence microscopy was used in one of them. RESULTS: Most of the
      cases occurred as well-defined nodular lesions, whose presumptive clinical
      diagnosis was adnexal or cystic pathology. All were treated surgically. The
      epiluminiscence microscopy showed a pattern of homogenous whitish-blue coloring.
      All the cases had a myxoid matrix and most also had a chondroid one. Five of the
      eight cases were apocrine, one of them with follicular and sebaceous
      differentiation. DISCUSSION: The chondroid syringoma is usually a small-sized
      skin tumor, frequently on the head and neck. The dermatoscopy does not seem to
      supply any specific trait to this lesion. The microscopic examination of these
      lesions reveals tubuloalveolar and glandular type structures positioned as islets
      within a fibroadipose, chondroid, myxoid or hyaline stroma. The final treatment
      of these tumors is surgical. As a general rule, it is a benign tumor. Some
      authors have proposed the term of atypical mixed tumor of the skin for those
      chondroid syringomas with histological traits of malignancy but without evidence
      of metastasis.

PMID- 17173761
TI  - [Adenoid cystic carcinoma].
AB  - Adenoid cystic carcinoma is an uncommon tumor of the head and neck. Although it
      is mainly located in the salivary gland, a skin location has also been described.
      Metastases are rare, but 50 % of the cases relapse. A 65-year-old male patient
      had a lesion in the upper lip. After resection, the histological diagnosis was
      adenoid cystic carcinoma. Treatment was completed with radiotherapy. Ten years
      later, a nodule was detected in the neck. Its histological diagnosis was
      lymphatic metastasis due to adenoid cystic carcinoma. Primary cutaneous adenoid
      cystic carcinoma is a very uncommon tumor in which treatment consists in
      extensive local excision with free margins. Radiotherapy is not curative and
      should be reserved for palliative treatments. Multicenter, prospective studies
      are necessary to determine the best treatment and especially the adjuvant
      treatment for adenoid cystic carcinoma.

PMID- 17173762
TI  - [Myxoid pleomorphic fibroma of the skin].
AB  - Pleomorphic fibroma of the skin was described by Kamino et al 1 in 1989. It is a
      benign fibroblastic proliferation with cytologic atypia. This article describes a
      case of a myxoid variant of pleomorphic fibroma of the skin.

PMID- 17173763
TI  - [Erythrodermic lichen planus pemphigoides].
AB  - Lichen planus pemphigoides is a clinico-histological subtype of lichen planus in
      which there are bullous lesions similar to those of bullous pemphigoid. Lichen
      planus is included among the rare causes of erythroderma. We present a case of
      erythrodermic lichen planus pemphigoides in a 49-year-old female patient who
      satisfactorily responded to treatment with cyclosporine. A detailed physical
      examination and immunofluorescence study are key to the diagnosis of lichen
      planus pemphigoides.

PMID- 17173764
TI  - [Scurvy and acquired ichthyosis associated to Whipple's disease].
AB  - The skin manifestations, except for hyperpigmentation, are uncommon in Whipple's
      disease (WD). We present the case of a 48-year-old male with chronic diarrhea and
      long course general syndrome associated to neurological manifestations. Skin
      examination revealed lesions in the lower limbs and gums that were clinically
      consistent with scurvy and were confirmed by histological study and measurement
      of blood vitamin C levels. Furthermore, he had lesions that were clinically and
      histologically consistent with acquired ichthyosis. The digestive tract biopsy
      study showed non-necrotizing epithelioid granulomas without the presence of PAS
      positive macrophages. The patient was diagnosed of Whipple's disease through the
      identification of genomic fragments of Tropheryma Whippelii by PCR in duodenal
      samples. He was treated with antibiotics for two years with resolution of the
      cutaneous and digestive picture but with partial improvement of the neurological
      symptoms. In the literature reviewed, we did not find any case of acquired
      ichthyosis associated to WD and only one of scurvy secondary to this rare
      disease.

PMID- 17173765
TI  - [Adult Still's disease with atypical skin manifestations].
AB  - Adult Still's disease (ASD) is an uncommon inflammatory disease of unknown
      etiology. It is characterized by the triad of intermittent high fever, evanescent
      rash and polyarthralgia or polyarthritis. We present the case of a 29-year-old
      woman with ASD and persistent erythematous papule on neck and upper part of the
      trunk. The presence of fixed lesions is not characteristic of ASD, but its
      appearance during development of the disease suggests that they are a
      manifestation of it. Recently, other skin manifestations of ASD have been
      published, but they are not well-known.

PMID- 17173766
TI  - [Juvenile multiple xanthogranuloma in a patient with Langerhans cell
      histiocytosis].
AB  - We present the case of a 10-week-old girl who had erythematous papules with a
      yellowish hue from birth with diagnosis of Langerhans cell histiocytosis, that
      was accompanied by a lytic lesion in the skull and hepatic involvement. After
      several months of treatment with prednisone and vinblastine with skin and
      systemic improvement, several rounded erythematous papules with a yellowish hue
      appeared in the right cheek. The biopsy showed a histiocytic infiltrate with
      positivity for CD68 and negative staining for S100 and CD1a, with a final
      diagnosis of juvenile xanthogranuloma. This association has been previously
      described in the literature in few cases. Although several hypotheses have been
      suggested, the causal relationship between both entities has still not been
      demonstrated.

PMID- 17173767
TI  - [Follicular keratosis and multiple myeloma].
AB  - Follicular keratosis may be a rare paraneoplastic disease having unknown
      etiopathogeny that is sometimes associated to myeloma whose diagnosis and
      evolution follow a parallel course. We describe the case of a 57-year-old female
      patient diagnosed of multiple myeloma 8 years ago. She developed generalized
      follicular hyperkeratotic spicules coinciding with leukemization of the myeloma.

PMID- 17173768
TI  - [Necrobiotic xanthogranuloma with scleroatrophic lichen associated with
      paraproteinemia].
AB  - Necrobiotic xanthogranuloma (Xn) with paraproteinemia is a
      histiocytoxanthomatosis (non-X histiocytosis) that affects the dermis and
      subcutaneous tissue of the face and less frequently the trunk and limbs. We
      present the case of a 58-year-old woman with a previous background of IgG
      (lambda) paraproteinemia and multiple autoimmune diseases, that associate
      clinically and histologically typical lesions of Xn on face, neck and limbs and
      of lichen sclerosus et atrophius (LEA) on skin and mucosae. The treatments
      performed were ineffective, the Xn lesions followed a chronic and progressive
      course with increased number, size and ulceration of them. The paraproteinemia
      has remained stable since it was diagnosed eight years ago. We have not found the
      association of Xn with paraproteinemia and SAL described in the literature. We
      review the characteristics of this rare disease and its possible pathogenic
      mechanisms.

PMID- 17173769
TI  - [Umbilicated papules on genitals in two siblings].

PMID- 17173770
TI  - [Brown erythematous papules on trunk and limbs].

PMID- 17173771
TI  - [Mondor's disease].

PMID- 17173772
TI  - [Friction blisters after resuscitation maneuvers].

PMID- 17173773
TI  - [Indicators of dermatology out-patient clinic visit].

PMID- 17173774
TI  - [Usefulness of 111In-oxine labelled platelets in the management of febrile
      syndrome in dialysis patients with non-functional renal allografts].
AB  - AIM: To evaluate the usefulness of 111In-oxine-labelled platelet scan in the
      therapeutic management of prolonged febrile syndrome in dialysis patients with a
      non-functional renal allograft. MATERIAL AND METHODS: One hundred and fifty-eight
      patients (94 men, 64 women; mean age 44 +/- 9 years) were studied. Duration of
      fever was 42 days (range 7-112). A total of 68 % of the patients (107/158) were
      on low doses of corticosteroids (<10 mg/day). Platelet scans were performed 48
      hours after reinjection of 111In-ixone-labelled platelets. A platelet uptake
      index (PUI) was calculated by dividing the cpm/pixel in the allograft by the
      cpm/pixel in a mirror background. A PUI > or = 1.5 was considered as threshold
      for immunological fever. The final diagnosis of immunological fever was
      established when it disappeared after transplantectomy, embolization or high
      doses of corticosteroid therapy. Fever of non-immunological origin was
      established when it disappeared after antibiotic therapy. RESULTS: In 102/158
      patients the fever was considered of immunological origin. In 56/158 patients the
      fever was considered of non immunological origin. Sensitivity and the specificity
      of the platelet scan was 80 % and 100 %, respectively. All those patients
      considered as having fever of immunological origin who had PUI <1.5 had been
      using corticosteroids during platelet scan. CONCLUSION: 111In-labelled platelet
      scintigraphy is a useful technique in the therapeutic management of prolonged
      febrile syndrome in dialysis patients with non-functional renal allograft. The
      use of corticosteroids can reduce the sensitivity of 111In- labelled platelet
      scan.

PMID- 17173775
TI  - [Impact of FDG-PET in therapeutic management of patients with suspected
      recurrence of head and neck cancer].
AB  - OBJECTIVE: This study aims to evaluate the impact of Positron Emission Tomography
      on therapeutic decisions in patients with suspicion of recurrence of head and
      neck cancers. MATERIAL AND METHODS: The diagnostic and therapeutic impact of FDG
      PET was evaluated in 59 of 60 studies performed in a sample of 54 patients. The
      impact was graded on five levels (high, moderate, low, no impact and negative
      impact) following the Hicks et al. classification modified by us. RESULTS: The
      FDG-PET impact was high in 28 studies (47.46 %), moderate in 7 (11.86 %), low in
      20 (33.90 %), no impact in 3 (5.09 %) and finally negative impact in 1 study
      (1.69 %). CONCLUSIONS: FDG-PET is useful in the management of patients in 59.32 %
      of the studies with indeterminate physical examination and conventional imaging
      tests. This paper supplies new data since we did not find any studies showing
      statistical results on therapeutic impact of FDG-PET in head and neck cancers in
      a systematic review of the literature made by our group.

PMID- 17173776
TI  - [Evaluation of efficacy and clinical impact of FDG-PET on patients with suspicion
      of recurrent cutaneous melanoma].
AB  - AIMS: To evaluate the efficacy and clinical impact of positron emission
      tomography with 18F-FDG (FDG-PET) in patients with suspected recurrent melanoma.
      MATERIALS AND METHODS: We studied 105 patients with melanoma and suspicion of
      recurrent melanoma by clinical symptoms in 38 cases or equivocal/positives
      morphological tests (TC, MR, US) in 77 cases. In all patients a whole body scan
      was performed with FDG-PET (ECAT HR +) after an intravenous injection of 444-518
      MBq of 18F-FDG, in normoglucemia conditions, and previous administration of
      muscular relaxant, hydration and diuretic. Images were evaluated by 2 dxpert
      nuclear physicians and were analysed qualitatively and semiquantitatively. In 48
      cases the results were confirmed by histology and clinical evolution (follow-up
      period >12 months) and imaging tests in 57 cases. RESULTS: Prevalence of
      recurrent melanoma was 63.8 %. Sensitivity, specificity, PPV, NPV and accuracy of
      FDG-PET was 97 %, 97.2 %, 98.5 %, 82 % y 94.7 % respectively. FDG-PET had led to
      a management change in 48 cases (38 %). CONCLUSIONS: FDG-PET has high clinical
      impact in patients with suspicion of recurrent melanoma, and should be
      incorporated in the diagnosis protocols, before making therapeutic decision.

PMID- 17173777
TI  - [Iatrogenic lung microembolism detected by 18FDG PET/CT].
AB  - We present the cases of two oncology patients: a male with Hodgkin's disease
      after completion of chemotherapy, and a woman recently diagnosed of melanoma, who
      underwent positron emission tomography/computed tomography (PET/CT) with 18F-FDG
      for therapeutic monitoring and initial staging, respectively. In both cases,
      hypermetabolic foci of 18F-FDG in lung parenchyma were found, without morphologic
      abnormalities in CT. These findings would have been consistent with lung
      pathology in the absence of any anatomic correlation. Combined PET/CT
      interpretation was of lung microembolisms probably originated at the injection
      site.

PMID- 17173779
TI  - [SAPHO syndrome].
AB  - We report two cases, one 23 and one 27 year old man, with several years
      background of sternal and sternoclavicular joints pain, respectively. The
      laboratory tests were normal. Based on the clinical, radiologic and scintigraphic
      findings, SAPHO syndrome was diagnosed. Bone scintigraphy makes it possible to
      obtain a whole body scan in a single whole body scan, and can be used for
      differential diagnosis of other osteoarticular diseases and for evolutive control
      and therapeutic response.

PMID- 17173778
TI  - 111In-Pentetreotide uptake in a follicular adenoma of the thyroid gland: a
      pitfall for 111In-Pentetreotide scintigraphy.
AB  - A patient with suspicion of a neuroendocrine tumor of the pancreas underwent a
      somatostatin receptor scintigraphy using 111In-Pentetreotide. 111In-pentetreotide
      scintigraphy showed discrete uptake of the radiotracer in the head of the
      pancreas and focal uptake in the right upper thyroid lobe. Tracer uptake in the
      24h planar image was higher compared to the 4h image, and decreased after 48
      hours. Normal thyroid tissue and thyroid disorders, such as cancers, Hashimoto's
      thyroiditis, and adenomas often show increased uptake of 111In-pentetreotide
      resulting in a possible false positive interpretation in patients with
      neuroendocrine tumor. Adding a 48h planar image might contribute to the
      differential diagnosis between benign or malignant lesions, as in the present
      case where the uptake decreased in an adenoma after 48 hours.

PMID- 17173780
TI  - [Unexpected renal uptake in a 123I-MIBG study].

PMID- 17173781
TI  - Fecal impaction detection on a bone scan.

PMID- 17173782
TI  - [Atlas of isotopic renography images in the renal transplant complications].

PMID- 17173783
TI  - [The central clinical services of a transplanting hospital and cadaveric organ
      donation].

PMID- 17173784
TI  - [Positron emission tomography with fluordesoxyglucose-F18 in follow-up of
      endometrial cancer].
AB  - OBJECTIVE: To assess the utility of FDG-PET in the follow-up of patients treated
      for endometrial cancer and with suspicion of recurrence according to conventional
      imaging methods (CT, MRI) and/or elevation of serum tumour markers. MATERIALS AND
      METHODS: Between April 2002 and December 2005, eleven patients underwent 17 FDG
      PET studies (six with 2 studies); mean age was 63.4 yrs (range, 52-69 yrs) and
      time since diagnosis ranged from 11 months to 12 yrs (mean of 56 months).
      Initially, seven patients were in stage I, three in stage III and one in stage IV
      (FIGO classification). Histologically, they corresponded to 8 endometrioid
      carcinomas and 3 non endometrioid carcinomas. RESULTS: FDG-PET showed
      infradiaphragmatic uptake in 3 patients and disseminated disease in 7 cases. FDG
      PET showed no uptake in one patient. CT (n = 7) or MRI (n = 7) detected
      infradiaphragmatic lesions in 5 patients and visceral lesions in 2. In 11
      patients, tumour markers were elevated (CA125, n = 9; CA19.9, n = 2; CA15.3, n =
      2). In 7 patients, FDG-PET modified the information yielded by conventional
      imaging techniques and in 4 patients, the FDG-PET contributed no additional
      information. In 2 patients, histologic confirmation of the lesions was obtained
      and in 9 patients, there were clinical follow-up (from 3 to 20 months, mean of
      8.7 months) and imaging studies. CONCLUSIONS: FDG-PET is superior to CT and MRI
      for detecting recurrences in the follow-up of patients with endometrial cancer.

PMID- 17173785
TI  - [Hyperemic reactivity scintigraphy in endothelial function].
AB  - OBJECTIVE: The aim of this study was to compare a recently described method to
      evaluate endothelial function; the hyperemic reactivity scintigraphy (HRS) with
      the ultrasonographic flow-mediated dilatation (FMD) in brachial artery and its
      relationship with myocardial SPECT. METHODS: 42 consecutive patients that
      underwent myocardial scintigraphy were included. Thirty-six patients had
      simultaneous measurement of FMD. Both studies were obtained after 5 minutes
      occlusion of the upper arm with a blood pressure cuff inflated at 250 mmHg. HRS
      was performed dynamically at rate 1 frame/sec during 3 minutes after intravenous
      injection of 740 MBq of Tc-99 sestamibi. Time-activity curves allowed obtaining
      the following indexes: medium hyperemic activity/medium contrallateral activity
      (MHA/MCA) and maximum hyperemic activity/maximum contrallateral activity
      (MxHA/CxHA). RESULTS: In 13 patients SPECT was normal. Twenty-nine patients had
      perfusion defects in scintigraphy. There was relationship between the FMD and the
      MHA/MCA (r = 0.23; p = 0.018) and the FMD and the MxHA/CxHA (r = 0.18; p = 0.05).
      Patients with alterations in the SPECT had an index MxHA/CxHA lower than patients
      with normal SPECT (1.8 +/- 0.2 vs 1.5 +/- 0.4; p = 0.04). We did not find
      relationship between FMD and alterations in SPECT. CONCLUSIONS: There is
      relationship between FMD and HRS. HRS is lower in patients with perfusion defects
      in the SPECT. HRS could provide additional value to myocardial scintigraphy.

PMID- 17173786
TI  - [Evaluation of renal lesions using 99mTc-DMSA in children with urinary tract
      infection and the relation with vesicoureteral reflux].
AB  - OBJECTIVE: Paediatric patients with urinary tract infection (UTI) have risk of
      developing renal scarrings. Although it is known that vesicoureteral reflux (VUR)
      predisposes to UTIs and it seems to have an important role in the development of
      renal lesions, some recent published studies question that relation. The aim of
      the study was to evaluate renal scarring by using renal scintigraphy 99mTc-DMSA
      and see the relation with or without the presence of VUR. MATERIAL AND METHODS:
      We evaluated retrospectively a total of 230 patients (460 renal units), mean age:
      11 months (range: 12d-5y), with UTI probed by urinoculture. All were studied with
      voiding cistourethrography (MCU) to evaluate the presence or absence of VUR.
      Patients were evaluated with 99mTc-DMSA scan 6 months after UTI to determine if
      UTI caused renal scarring. RESULTS: Renal scans with 99mTc-DMSA 6 months post
      infection were abnormal in 62 renal units, affecting 54 patients (23 %). From all
      patients studied, 110 were diagnosis of VUR being affected 161 renal units, 43 of
      them (27 %) presented renal scarrings. From the remaining 120 patients without
      VUR that is 240 renal units, 19 of them (8 %) presented parenchymatous damage.
      CONCLUSION: Renal scarring resulting from UTI are in some cases related to VUR,
      but sometimes are caused by the infection itself. Not all patients with VUR
      develop renal lesions, and neither the presence of VUR always predispose children
      to renal lesions. MCU and direct isotopic cystography are useful for diagnosis of
      VUR but we shouldn't avoid 99mTc-DMSA scan in the management of children with
      UTI.

PMID- 17173787
TI  - [Prognostic utility of scintigraphy with 99mTc-HMPAO labelled leukocytes in
      inflammatory bowel disease].
AB  - OBJECTIVE: The inflammatory bowel disease (EII) has a chronic evolution with a
      frequent relapses. There is no specific diagnosis method to detect the patients
      with a high risk to relapse. The aim of the work was to analyse the prognostic
      value of 99mTc-HMPAO leukocyte scintigraphy (LS) performed during an acute attack
      of EII. MATERIAL AND METHODS: 18 patients (mean age 32 +/- 10 years) admitted for
      an acute attack of EII has been prospectively studied (5 ulcerative colitis [UC]
      and 13 Cronh's disease [CD]), excluding patient with prior steroids or
      immunosuppressive therapy during the last year. LS were obtained in basal
      conditions and following 3 weeks of steroid treatment and the scintigraphic
      activity index (SAI) has been calculated. Colonoscopy has been done in all
      patients, and CDAI in CD and Truelove index in UC have been calculated. Patients
      were followed up for 1 year. In the evolution the therapy requirements as well as
      the good response to initial treatment have been evaluated. RESULTS: All patients
      with UC and 4 patients with CD showed a SAI decrease > 50 % and all had a good
      clinical evolution. Only 2 out of the 9 patients with CD showing a IAG decrease <
      50 % and had a good clinical evolution, the 7 remaining required additional
      medical treatment (immunosuppressors or surgery). CONCLUSION: LS may be of
      prognostic value in the management of EII. A SAI decrease > 50 % at 3 weeks of
      steroid treatment indicates a good clinical evolution.

PMID- 17173788
TI  - [Value of radioguided surgery with dobutamine 99mTc-MIBI in persistent secondary
      hyperparathyroidism].
AB  - 99mTc-MIBI is a radiopharmaceutical that has been successfully used for the
      detection of hyperfunctioning parathyroid glands and for radioguided surgery
      techniques. We report on the case of a 55 year old woman in hemodialysis, with
      secondary persistent hyperparathyroidism after total parathyroidectomy. The
      conventional double-phase 99mTc-MIBI parathyroid scintigraphy was negative. The
      study was repeated after sensibilization with intravenous low-dose dobutamine
      showing an area of increased focal uptake in the lower cervical region. With this
      finding, radioguided 99mTc-MIBI surgery was performed after dobutamine
      administration, using a hand held gamma probe. The technique was considered
      successful with the resection of parathyroid cervical tissue which was further
      confirmed as nodular hyperplasia. We conclude that this methodology has the
      potential of being a an useful tool for the intraoperative localization of
      remanent tissue in patients with secondary persistent/recurrent
      hyperparathyroidism.

PMID- 17173789
TI  - [Finding with scintigraphy with 67-gallium citrate of Paget's disease in a woman
      with gastric lymphoma].

PMID- 17173790
TI  - [Rhabdomyolysis after treatment with atorvastatin detected by bone scintigraphy].

PMID- 17173791
TI  - [Introduction to the molecular imaging].

PMID- 17173792
TI  - [Metabolic therapy].

PMID- 17173793
TI  - [Alcohol: third risk factor in the developed countries].

PMID- 17173795
TI  - [Commentary. Should palliative treatment programs be supported by primary care
      teams?].

PMID- 17173794
TI  - [Palliative care support teams and the commitment of primary care teams to
      terminally ill patients in their homes].
AB  - OBJECTIVE: To find out if the activity of palliative care support teams (PCST)
      does not negatively influences the performance of the primary care "care of
      terminally ill patients" service. PARTICIPANTS: Terminally ill patients cared for
      at home. DESIGN: Multicentre observational study. MAIN MEASUREMENTS: The observed
      variable is the increase in the number of registered patients in primary care,
      and the number of patients covered between the years 2002 and 2003 and the 4
      intervention variables are: total visits, joint visits, assessments, and teaching
      sessions. RESULTS: The number of patients covered in 2002 was 41.19%, increasing
      to 45.44% in 2003. The activity rate of the PCST for each 100 000 inhabitants was
      526 home visits in 2003, 86.15 joint visits, 313.68 professional assessments, and
      23.14 teaching sessions. The joint visits and the teaching sessions were strongly
      associated with an improvement in the coverage of primary care (Pearson
      correlation of 0.784 and 0.759, respectively). The total visits were moderately
      associated (0.525) and the assessments were weakly associated (0.245).
      CONCLUSIONS: Joint visits and teaching sessions of a PCST are associated to an
      increase in the activity of primary care teams. Assessments and total visits did
      not have a negative influence.

PMID- 17173796
TI  - [Analysis of studies published on hypertension treatment non-compliance in Spain
      between 1984 and 2005].
AB  - OBJECTIVE: To analyse therapy non-compliance in hypertension treatment in Spain,
      after a review of studies published between 1984 and 2005. DESIGN: Systematic
      review. DATA SOURCES: Data searches used Internet (Medline and Spanish index on
      doctoral these), a manual search of several Spanish journals, and bibliographic
      references to compliance from detected articles and through personal contact with
      experts. Descriptors used were: hypertension and patient compliance, compliance,
      adherence, patient drop-outs, treatment refusal, and their combinations.
      SELECTION OF STUDIES: Studies conducted in Spain and published between 1984 and
      2005 were included, along with original articles, congress abstracts or doctoral
      theses, which used as a method of measurement pill count or counting of spaces in
      electronic monitoring systems, and which defined as non-compliers patients with a
      compliance percentage <80% and >110%. DATA EXTRACTION: The percentage of non
      compliers was calculated, with 95% confidence intervals and weighted average of
      the percentage of non-compliers in each study. RESULTS: Twenty-six research
      studies published in Spain, excluding 2 analytical studies, were found. A total
      of 3553 patients with hypertension were included, of which 32.53% were non
      compliers (n= 1156; 95 CI, 29.83-35.23) and 67.47% were compliers (n=2397; 95%
      CI, 65.67-69.27). The weighted average of non-compliance was at 32.78%.
      CONCLUSIONS: The percentage of therapy non-compliance in the treatment of
      hypertension in Spain has fallen in recent years, although it continues to be
      high.

PMID- 17173797
TI  - [Heterozygous family hypercholesterolemia: study of use of statins under clinical
      practice conditions].
AB  - OBJECTIVES: To compare the use profile of statins in patients with clinical
      diagnosis of heterozygous family hypercholesterolaemia (HFH) and the use profile
      of the general population treated with statins. DESIGN. Retrospective,
      observational study. SETTING: Galician Health Service, Spain. PARTICIPANTS:
      Patients under 65 years old treated with statins. MAIN MEASUREMENTS: In patients
      with HFH: number of patients, age, gender, statins used and defined daily dose
      per patient and day (DDD/patient/day). Variables in the rest of the population
      treated with statins: number of patients, statins used and DDD/patient/day.
      RESULTS: In a sample of 331 under-65 patients with HFH, 185 were men (55.86%) and
      146 women (44.14%). Their average age was 44.56 years old (95% CI, 43.33-45.80),
      without statistically significant differences between men and women. Relevant
      differences in the daily mean consumption (DDD/patient/day) of statins between
      the studied sample and the rest of the under-65 population treated with statins
      were found (3.03 DDD/patient/day [95% CI, 2.70-3.36] vs 1.33 DDD/patient/day [95%
      CI, 1.16-1.40]; P< .001). These differences were caused by atorvastatin: 70% of
      HFH patients were being treated with atorvastatin (versus 37.6% of the rest of
      the population treated with statins). Differences in daily mean consumption of
      atorvastatin between HFH and the rest of the statin-treated population were also
      found (3.58 DDD/patient/day [95% CI, 3.15-4.02] vs 1.64 DDD/patient/day [95% CI,
      1.37-1.90]; P< .001). CONCLUSIONS: The DDD/patient/day of statins in HFH patients
      is double that of the rest of the population treated with statins. The different
      pattern of use of atorvastatin in HFH is the main reason for these results.

PMID- 17173798
TI  - [Female sexual function and related factors].
AB  - OBJECTIVES: To appraise female sexual function and to describe the factors that
      most commonly accompany dysfunction. DESIGN: Transversal, descriptive study.
      SETTING: Primary care. PARTICIPANTS: Two-hundred and twenty-three women from 18
      to 76 seen at an urban health centre between November 2004 and February 2005 and
      who wanted to take part in the study. MAIN MEASUREMENTS: These were collected in
      an anonymous questionnaire structured in 5 sections with 53 items. The
      questionnaire comprised social and economic, cultural and life-style variables;
      female sexual function (FSF); and perception of own state of health (SF-12). A
      binary logistical regression analysis was run. RESULTS: Female sexuality reaches
      its maximum expression at 30-35 years (FSF=30.0, 95% CI, 28.3-31.6). Risk factors
      for sexual dysfunction were: age over 44 and religion (OR, 6.5; 95% CI, 2.8-15);
      physical component on the SF-12 below 37 (OR, 3; 95% CI, 1.3-7.2); mental
      component on the SF-12 below 31 (OR, 3.1; 95% CI, 1.2-7.8). Not having a stable
      partner was a risk factor for arousal (OR, 9.6; 95% CI, 2.8-24.0); for
      lubrication (OR, 9.3; 95% CI, 4.0-21.5); for orgasm (OR, 8.8; 95% CI, 3.1-24.8);
      and for dyspareunia (OR, 8.9; 95% CI, 3.9-20.5). It was not a risk factor for
      desire or satisfaction with sexual life. CONCLUSIONS: The profile of sexual
      dysfunction consisted of a woman aged over 44 without a stable partner, who
      practised religion, was unemployed and had perception of low quality of life.

PMID- 17173799
TI  - [Need for primary care training in rare diseases].
AB  - OBJECTIVES: The problem of the need for primary care (PC) training in rare
      diseases (RD) is approached through a qualitative research study that tries to
      define its relevance and to identify the need for RD training in PC. METHODS: By
      means of naturalistic research methods (in-depth interviews and group dynamics),
      we tried to discover the personal and professional connotations of PC training in
      RD in the rural and urban areas of the Community of Madrid, Spain. The areas
      explored by means of structured interview were: challenges and RD definition;
      professional experience with RD; relevance of PC for RD; training and information
      in RD; needs and demands for RD in PC. RESULTS: We found no differences between
      the rural and urban groups nor between different professional categories. The RD
      concept was relatively unknown and difficulties arose in understanding the
      magnitude and overall importance of these diseases. Nor did the RD concept
      express the severity or the repercussions of these diseases. RDs awoke little
      professional interest, in contrast with the human interest aroused. CONCLUSIONS:
      The professionals interviewed thought that undergraduate training was sufficient,
      and rejected postgraduate training as unnecessary and unfeasible. The search for
      active information through Internet was the best way to obtain data to optimize
      criteria for patient referral. As such, the Information System for Rare Diseases
      in Spanish (Sistema de Informacion de Enfermedades Raras en Espanol, SIERE)
      (http://iier.isciii.es/er) meets the demands for information.

PMID- 17173800
TI  - [The specific framework of clinical practice in family medicine: implications for
      practice and training].

PMID- 17173801
TI  - [Screening for factors relating to the development of mental disorders in the
      geriatric population (PSICOTARD)].
AB  - OBJECTIVES: To detect the physical, psychological, social-demographic, and
      functional factors that may involve risk of developing mental disorder in the
      elderly, to determine the magnitude of each factor and to do the groundwork for a
      future longitudinal study that will enable us to define the elderly with
      psychological fragility in the autonomous region and to design predictive models
      for mental deterioration in the elderly. DESIGN: Descriptive study based on
      personal interviews by professionals using a standardised method. SETTING: Twenty
      eight primary care health centres in the province of Huesca, Spain, with an
      ageing rate over 24.6%. PARTICIPANTS: Three-hundred and twenty-six patients over
      64 years and resident in the province of Huesca, Spain. INTERVENTION: Personal
      interview conducted by health professionals (30 family doctors and a trainee
      psychologist). The following will be appraised: the presence of cognitive
      impairment (Mini-Mental State Examination), depression (Yesavage Geriatric
      Depression Scale), anxiety (Goldberg Scale of Anxiety), and presence of
      delusions, hallucinations, obsessions and hypochondria (Geriatric Mental State
      GMS). MAIN MEASUREMENTS: The prevalence of the risk factors will be calculated:
      social and demographic variables (age, sex, marital status, education, living
      alone), functional status (Barthel index), the severity of physical disability
      (Cumulative Illness Rating Scale), pathological records (somatic and
      psychological), and stressful life events in the preceding year. A logistical
      regression model will be calculated to determine the weight of the effect of each
      factor adjusted for all the rest. Individual risk will be calculated for the
      development of each mental disorder (depression, anxiety, cognitive
      deterioration/dementia, psychotic symptoms, obsessions). DISCUSSION: The
      reliability of the questionnaire is ensured by use of diagnostic tests of proven
      validity and reliability, prior training of researchers and use of a data
      gathering pilot study.

PMID- 17173802
TI  - [Can we benefit from determination of the ankle-arm index in primary care
      consultations?].

PMID- 17173803
TI  - [Ten years of early breast cancer detection programme in the Almeria district].

PMID- 17173804
TI  - ["News alert": a Google search engine service. Its utility in geriatrics and
      gerontology].

PMID- 17173805
TI  - [Metabolic syndrome at an urban primary care centre. Comparative analysis with
      the ATP III and IDF criteria].

PMID- 17173806
TI  - [Influence of age and sex on information for terminal-stage patients].

PMID- 17173807
TI  - [Usefulness of the Department of Pathological Anatomy in a programme caring for
      HIV/AIDS patients].

PMID- 17173808
TI  - [Adolescents and alcohol. Primary prevention].

PMID- 17173809
TI  - [X conference of semFYC residents].

PMID- 17173810
TI  - [Organisational issues in implementing clinical trials in primary care].
AB  - OBJECTIVE: To identify health professionals concerns on the organisational issues
      of a randomised clinical trial. DESIGN: A qualitative cross-sectional,
      descriptive study. SETTING: Primary Care Area 11, Madrid, Spain. PARTICIPANTS:
      Twenty-four doctors and nurses from 4 primary care teams. METHOD: Three planning
      meetings with researchers. Design of an anonymous self-administered questionnaire
      to collect researchers' perceptions on design, method, and organisation during
      the implementation of a clinical trial. RESULTS: The prestige of being involved
      in a multi-centre nationwide project, the training sessions offered, a primary
      care research topic, a working team model of doctor and nurse, and the support
      provided by team from the 11th Area, were the main organisational incentives.
      Lack of time, increased clinic workload, and methodological difficulties are
      discouraging issues. 79.2% (19/24) of the researchers returned the questionnaire.
      94.7% (18/19) considered themselves highly motivated. 84.2% (16/19) of
      researchers, the time required to complete recruitment was reasonable. The 57.9%
      (13/19) spent 20-25 minutes collecting data at the interview. Cooperation between
      doctors and nurses had been effective for 68.4% (13/19) of researchers. 89.4%
      (17/18) considered that support from the Area 11 organisers was useful.
      CONCLUSIONS: Organisational barriers for implementation are: complexity of data
      collection at the recruitment interview, design and methodological issues too
      unrealistic for a primary care setting, and lack of time and extra workload at
      consultations. The factors that make organisation easier are: having a high level
      of motivation, sharing workload with other professionals, and support provided by
      organisers of the trial.

PMID- 17173811
TI  - [Clinical trials in primary care].

PMID- 17173812
TI  - [Study of primary care health needs through family health diagnosis].
AB  - OBJECTIVE: To assess the health needs of the eligible public population of the
      Mexican Institute of Social Security (IMSS). DESIGN: Observational, descriptive,
      transversal study. SETTING: Family Medicine Unit number 8 of the IMSS, in the
      city of Tlaxcala, Mexico. PARTICIPANTS: A sample of 1200 families using multi
      stage sampling, between October 1999 and March 2000. MAIN MEASUREMENTS: The
      designed and validated questionnaire on "Family health diagnosis" was used.
      RESULTS: A 19.2% of the families had a very low socio-economic level, and 14.9%
      of subjects were not entitled to Social Security. Functional illiteracy in at
      least one member was found in 12.6% of the families. According to the family
      Apgar, 93% of families were functional and two-thirds of the families were
      classified as nuclear. About 51.1% and 36.9% of women used programs for detection
      of cervical/uterine and breast cancer, respectively. Only 25% of the adult
      population underwent the detection tests for diabetes mellitus and hypertension
      and 10.9% had a chronic disease. 56.4% of families considered the quality of
      health care good, and only 18.13% were satisfied with the care received.
      CONCLUSIONS: Identification of health needs through diagnosis of family health is
      useful as a basis for establishing a hierarchy of problems as well as for
      developing health programs that may facilitate greater equity in attention.

PMID- 17173813
TI  - [Benign prostate hyperplasia. Need to evaluate quality of life in the therapeutic
      process].
AB  - OBJECTIVE: To relate the symptoms of benign prostate hyperplasia (BPH) to their
      repercussions on quality of life. DESIGN: Multi-centred, observational,
      prospective study. SETTING: Primary care. PARTICIPANTS: Men with BPH in 2000
      2003. Inclusion criteria were: agreeing to take part, being aged 50-79, and
      having moderate symptoms evaluated by means of the IPSS questionnaire. EXCLUSION
      CRITERIA: Previous treatment for BPH and having a chronic or disabling illness
      that might affect perception of quality of life. The presence of irritative and
      obstructive symptoms was appraised. MAIN MEASUREMENTS: The IPSS questionnaire
      appraising predominant symptoms and, through the last question, quality of life
      was self-administered. Descriptive statistics were worked out and differences in
      proportions of the different groups were analysed by the chi2 test, with
      differences taken as significant at P < .05. RESULTS: We got 536 replies, with
      average age 66.2. Nycturia was the most common symptom, suffered by 88.1% of
      patients. A total of 256 patients (47.8%) had irritation as main clinical
      symptom, and 280 (52.2%), obstruction. On analysing repercussions on quality of
      life, it was found that obstructive symptoms were worse tolerated: 65.7% versus
      9.4% of the group with irritation. CONCLUSIONS: In treating BPH, we must bear in
      mind preferences of patients. They tolerate obstructive symptoms worse, and these
      are a criterion for referral to specialists and even surgery.

PMID- 17173814
TI  - [Prevalence of white-coat hypertension and masked hypertension in the general
      population, through home blood pressure measurement].
AB  - OBJECTIVE: To determine the prevalence of white-coat hypertension (WCH) and
      masked hypertension (MH) in the general population, by means of home blood
      pressure measurement (HBPM). DESIGN: Cross-sectional, descriptive study. SETTING:
      Four primary care centres. PARTICIPANTS: A sample of 1400 individuals over 18
      years old, selected from the Municipal Register of Inhabitants (Huelva, Spain)
      and randomised and stratified by age and gender. MAIN MEASUREMENTS: Two blood
      pressure (BP) measurements in clinic (CBP) and 12 measurements in a week of BP by
      HBPM were performed (OMRON 705-CP). Pressure was seen as normal when CBP means
      were <140/90 mm Hg and HBPM was <135/85 mm Hg. WCH was defined as when CBP was
      >140/90 mm Hg and HBPM <135/85 mm Hg, and hypertension when CBP was >140 mm Hg
      and HBPM >135/85 mm Hg or patients were in treatment for hypertension. MH was
      when CBP was <140/90 mm Hg and at home was >135 mm Hg and/or 85 mm Hg. RESULTS: A
      total of 1153 individuals (82.35% of the sample) with mean age of 45.4 (SD, 16.1)
      were included: 560 men and 593 women. The prevalence of MH was 8.9% (CI+/-1.6) in
      the general population and 9.8% (CI+/-3.2) in individuals with hypertension. WCH
      prevalence was 3.6% (CI+/-1.05) overall and 12.8% (CI+/-3.6) in hypertense
      patients, with its prevalence increasing steadily as age groups rose (P = .001).
      CONCLUSIONS: The prevalence of WCH in the general population is low, whereas the
      prevalence of MH is high.

PMID- 17173815
TI  - [Different uses of home blood pressure measurement in the diagnosis and
      monitoring of hypertension].
AB  - OBJECTIVE: To find differences between measurements of clinical blood pressure
      and self-monitored home blood pressure measurement (HBPM). DESIGN: Descriptive
      study developed in a general population census. SETTING: Primary care. SUBJECTS:
      A total of 1411 subjects > or =18 years old were selected by stratified
      randomized sampling. METHODS: A skilled nurse made 3 clinical blood pressure
      (CBP) measurements, and trained patients or their relatives in HBPM, doing 12 in
      one day. CBP and HBPM employed an electronic device (OMRON 705CP). RESULTS: A
      total of 12 HBPM from 1184 subjects (52% women) were completed, with a mean age
      of 47.6 (SD, 17.2); 195 subjects were known to have hypertension. White-coat
      effect was diagnosed in 14.9% of subjects with normal pressure, 22.3% of
      hypertense patients treated and 57.6% of subjects with suspicion of isolated
      clinical hypertension. Possible isolated clinical hypertension was diagnosed in
      10% of subjects without hypertension. White Coat normal pressure was found in
      2.3% of untreated subjects and 4.7% of subjects with treated hypertension. 20.7%
      of subjects with hypertension poorly controlled in the clinic were considered
      pseudo-refractory (11.4% at the end of dosage interval). 77% of subjects
      conducted HBPM on their own and 89% thought it easy to do so. CONCLUSION:
      Incorporation of HBPM into daily medical practice could avoid 20%-30% of possible
      mistakes in diagnosis and monitoring of hypertense patients.

PMID- 17173816
TI  - [Professional courses: something more than recognition?].

PMID- 17173817
TI  - [Complementary and alternative medicine and its contribution to the social and
      health system. What, why, and how].

PMID- 17173818
TI  - [Is fragility a fact in the over-80s? Prevalence study].

PMID- 17173819
TI  - [Finding the right platelet anti-aggregant prescription for type-2 diabetes
      patients, according to the ADA 2003 criteria].

PMID- 17173820
TI  - [MAPA and stratification of cardiovascular risk in hypertense patients in primary
      care].

PMID- 17173822
TI  - [Reducing cardiovascular risk in a table is not equivalent to reducing
      cardiovascular events].

PMID- 17173821
TI  - [Repercussions on caregivers of the chronically ill at home].

PMID- 17173823
TI  - [Pharmacogenetics I. Concept, history, objectives and areas of study].
AB  - There is great interindividual variability in the response to drugs, both in
      effectiveness and toxicity. Different patients respond differently to the same
      medication as a consequence of genetic and non-genetic factors. Pharmacogenetics
      represents the study of the individual pharmacological response based on the
      genotype. Its objective is to optimize treatment in an individual basis, thereby
      creating an individualized therapy, more safe and efficient, that will allow the
      clinician to select the correct drug, at the adequate dose, for the right
      patient. In the first part of this review we discuss several aspects of the
      relationship between genetics and therapeutic response, as well as the concept,
      history, objectives and different areas of study of pharmacogenetics.

PMID- 17173824
TI  - [Preliminary results of DERMATEL: prospective randomized study comparing
      synchronous and asynchronous modalities of teledermatology].
AB  - INTRODUCTION: There is considerable variability in the results of studies that
      evaluate diagnostic reliability in teledermatology. There are only two studies
      that compare the synchronous and asynchronous modalities of teleconsult in the
      same sample. We present the results of the pilot project DERMATEL, a study of
      diagnostic concordance that aims to increase the evidence of these aspects.
      MATERIAL AND METHODS: One-hundred-fifty.nine patients referred by the general
      practitioner in the first consult were randomized (algorithm 3:2:1) in three
      arms: asyncronous teledermatology (store-and-forward or SAF), synchronous
      teldermatology (real-time or VTC), and conventional consult (CC). We used high
      quality, fixed digital images in all cases. The patients on the VTC
      teledermatology arm were also evaluated by videoconference. Finally all patients
      attended a face-to-face consult, considered the gold standard of patient care. A
      second dermatologist evaluated the diagnostic and management concordance between
      the teleconsults and the face-to-face consults. RESULTS: One-hundred.forty-seven
      patients completed the study as follows: 74 in the SAF teledermatology arm, 47 in
      the VTC teledermatology arm and 26 in the conventional consult (control group).
      The teledermatological (SAF and VTC) and face-to-face evaluations were identical
      in 100 of 121 patients (82.6%). The errors were mild in 14 cases (11.6%) and
      severe in 7 (5.8%). The diagnostic concordance was very high (kappa=0,813). The
      errors grouped by diseases were as follows: 6/54 (11%) for tumors, 10/30 (33.3%)
      for inflammatory conditions, 1/20 (5%) for infectious diseases, 3/12 (25%) for
      alopecia/acne and 1/5 (20%) for others. There were 15 errors in the SAF
      teledermatology arm (20.3%) and 6 in the VTC teledermatology arm (12.8%); these
      differences were not statistically significant (chi2 1.12; p=0.288). CONCLUSION:
      The reliability of dermatological teleconsult is very high, especially for
      tumoral or infectious diseases. The synchronous interaction with audio requires
      more resources, is difficult to coordinate and its diagnostic efficacy is not
      superior to SAF teledermatology.

PMID- 17173825
TI  - [Influence of anxiety in diverse cutaneous diseases].
AB  - INTRODUCTION: The objective of the current study is to determine the levels of
      anxiety in patients with dermatological diseases compared to healthy subjects and
      the degree of anxiety in the different cutaneous diseases. MATERIAL AND METHODS:
      It is a descriptive study of a case series where 152 patients are selected, 20 of
      whom are healthy controls and the other 132 are patients that attend a
      Dermatology clinic. The patients are divided into 5 groups based on the cutaneous
      disorder for which they attend the clinic: chronic urticaria, acute urticaria,
      plaque psoriasis, atopic dermatitis, and a miscellaneous group (includes several
      diagnoses such as seborrheic keratosis, follow-up of multiple nevi,
      carcinomas...) where, a priori, anxiety does not influence these disorders.
      Spielberger State-Trait Anxiety Inventory (STAI) is administered to the
      participating subjects and the differences in State Anxiety Inventory (SAI) and
      Trait Anxiety Inventory (TAI) for the different groups are analyzed. Patients
      were asked to report any stressful event in the six months prior to the
      appearance of the disease that might have been a trigger, and they were also
      asked about history of psychiatric disorders or atopy. RESULTS: We observed
      significant differences in the means obtained in SAI and TAI in healthy subjects
      compared to patients. We obtained higher mean scores in SAI in patients diagnosed
      of atopic dermatitis, that were significant when compared with patients with
      chronic urticaria or other diseases. Forty-eight percent of patients with
      psoriasis and 38.89 % of patients with atopic dermatitis report a stressful event
      in the past six months compared to 11.54% of patients from the group with
      miscellaneous diseases and, additionally, patients with psoriasis and atopic
      dermatitis have the highest mean scores in the anxiety tests. Twenty-one percent
      of the 132 patients with cutaneous diseases report a history of psychiatric
      disorders, showing statistically significant higher mean scores in STAI.
      CONCLUSION: The findings show the comorbidity of psychiatric disorders in
      patients with chronic cutaneous diseases and the high levels of state and trait
      anxiety, mainly in patients with psoriasis and atopic dermatitis.

PMID- 17173826
TI  - [Necrotizing subcutaneous infection by Streptococcus agalactiae].
AB  - Necrotizing soft tissue infections constitute some of the most potentially
      threatening infections that may be acquired in the community or in the hospital
      milieu as they are associated with a high mortality rate. In most cases they are
      produced by Streptococcus pyogenes. We report a case of a necrotizing soft tissue
      infection caused by Streptococcus agalactiae (group B beta hemolytic
      streptococcus) that involved the leg of an elderly man with chronic lymphatic
      leukemia and diabetes mellitus. The lesions notably improved after initiating
      intravenous antibiotic treatment with amoxicillin-clavunate and clindamycin.

PMID- 17173828
TI  - [Porokeratosis in a patient with dermatomyositis].
AB  - There are several reports of porokeratosis in the context of immmunosuppressive
      diseases. These mainly include organ transplant, HIV infection, lymphomas and
      some inflammatory and autoimmune diseases commonly treated with immunosuppresive
      drugs or chemotherapy. Disseminated superficial actinic porokeratosis is the
      clinical variant of porokeratosis that most frequently develops in
      immunosuppressive states. We report a case of porokeratosis in a woman with
      dermatomyositis.

PMID- 17173827
TI  - [Atypical presentation of syringocystoadenoma papilliferum].
AB  - Syringocystoadenoma papilliferum is benign adnexal tumor derived from the sweat
      glands that is located in the head and neck in 70-80% of patients, and commonly
      presents as a papule or a solitary nodule. We report a case of
      syringocystoadenoma papilliferum with an atypical presentation given its location
      in the thigh and the peculiar histologic features, unrepresentative of this
      entity.

PMID- 17173829
TI  - [Mycobacterium marinum infection. Case report and review of the literature].
AB  - Atypical mycobacterial infections are increasingly important in immunosuppressed
      patients as well as in healthy hosts. The atypical mycobacterium that most
      commonly affects the skin is Mycobacterium marinum. The infection should be
      suspected upon the presence of ulcers, nodules or chronic plaques and a history
      of contact with fresh or salt water. Optimal therapy is yet to be established. We
      report a case of Mycobacterium marinum infection in a patient receiving
      immunosuppressive therapy that responded favourably to treatment with
      doxicycline. We review the different antibiotic regimens prescribed in the past
      years for the treatment of Mycobacterium marinum infection.

PMID- 17173831
TI  - [Cutaneous metastases from adenocarcinoma of unknown primary site].
AB  - Metastatic cancer of unknown primary site appears in 5-10% of oncologic patients.
      The primary tumor is usually discovered at autopsy and only in 27% of patients
      alive. Metastases from cancer of unknown primary site may be located in the skin
      and subcutaneous tissue and it is the dermatologist the first in evaluating these
      patients. We present a case of cutanoeus metastases from moderately
      differentiated adenocarcinoma of unknown primary site. The immunohistochemical
      study revealed positive staining for CEA and negative staining for PSA. The
      primary tumor could not be identified in spite of the imaging and endoscopic
      studies performed. Based on these studies we excluded a colorectal or prostatic
      origin and considered a pancreatic adencarcinoma as the possible primary tumor.
      Even though a minority of these patients will have a curable disease, the
      appropriate use of pathological diagnosis and selected imaging studies for an
      optimal management of patients with a tumor of unknown primary site should not be
      ignored.

PMID- 17173830
TI  - [Bart syndrome associated to lethal junctional epidermolysis bullosa (Herlitz
      form)].
AB  - We present the case of a newborn with congenital absence of skin in the anterior
      part of the left leg that shortly after developed bulla and erosions in hands,
      feet, ears, buttocks and mouth. The cutaneous biopsy and ultrastructural and
      immunohistochemical studies showed a subepidermal bulla in the lamina lucida,
      absence of hemidesmosomes and marked decrease of laminin 5, thus establishing the
      diagnosis of Bart syndrome associated to the Herlitz form of lethal junctional
      epidermolysis bullosa. Bart syndrome consists of congenital and localized absence
      of skin, nail abnormalities and mucoc-cutaneous bullae. It is usually associated
      to dystrophic epidermolysis bullosa. The Herlitz form of junctional epidermolysis
      bullosa is a rare variant, usually lethal that is produced by mutations in the
      genes coding for the anchor protein laminin 5. To our knowledge this is the
      second case that reports an association between Bart syndrome and lethal
      junctional epidermolysis bullosa and the first in which the results of
      immunofluorescence mapping are published.

PMID- 17173832
TI  - [Spontaneous cutaneous umbilical endometriosis].
AB  - Endometriosis consists of extrauterine endometrial growths. Although it is
      usually located in the pelvis it can also be found in other sites. Endometriosis
      of the skin is rare and the most frequent form develops over gynecologic or
      obstetric scars, although it may also appear spontaneously in the umbilical area.
      We present a 39-years-old woman with an umbilical nodule as a clinically
      characteristic form of spontaneous cutaneous endometriosis. The histopathological
      examination confirmed the clinical diagnosis.

PMID- 17173833
TI  - [Brooke-Spiegler syndrome: an heterogeneous entity].
AB  - The Brooke-Spiegler syndrome is a rare, autosomally dominant disease with a
      predisposition to develop different adnexal tumors. Clinically it is
      characterized by the presence of multiple cylindromas, trichoepitheliomas, and
      occasionally, spiradenomas. Although Brooke-Spiegler syndrome, familial
      cylindromatosis and multiple familial trichoepithelioma were initially described
      as separate entities, the recently identified identical mutations in the gene of
      cylindromatosis suggest that they represent fenotypic variations of the same
      entity. In this article we present the case of a woman and her daughter, both
      affected by this rare genodermatosis.

PMID- 17173834
TI  - [Annular red scaly plaque in the thigh].

PMID- 17173835
TI  - [Pink yellowish papules in neck and thorax].

PMID- 17173836
TI  - [Therapy with voriconazol for a case of chronic mucocutaneous candidiasis].

PMID- 17173837
TI  - [Ondansetron. A satisfactory treatment for refractory palmo-plantar pruritus].

PMID- 17173838
TI  - Asthma: objective assessment.

PMID- 17173839
TI  - Functional and phenotypic characterization of CD8+CD28+ and CD28- T cells in
      atopic individuals sensitized to Dermatophagoides pteronyssinus.
AB  - BACKGROUND: CD8+ T suppressor cells may play a role in immunoregulation. Recent
      studies have characterized this population by the lack of the CD28 molecule.
      These CD8+CD28 T cells differ phenotypically and functionally from CD8 + CD28 + T
      cells. Little is known about CD8 + CD28 cells in atopy. Our aim was to analyze
      the phenotype and functional properties of CD8 + CD28T cells in atopic and non
      atopic individuals. METHODS: Peripheral blood mononuclear cells (PBMC) were
      obtained after density gradient centrifugation. CD8 + CD28 and CD8 + CD28 + T
      cells were isolated using immunomagnetic beads. Relative percentages of these
      cells and expression of several phenotypic markers were analyzed by flow
      cytometry. Proliferation was assessed by thymidine incorporation in isolated
      populations and in co-cultures with PBMC using Dermatophagoides pteronyssinus as
      stimulus. Cytokine synthesis was evaluated in culture supernatants by cytometric
      bead array. RESULTS: The relative percentages of CD8+CD28 T cells and their
      phenotypic expression in atopic and non-atopic volunteers were not significantly
      different. However, CD8 + CD28 T cells showed greater proliferation than did
      CD8+CD28+ T cells when stimulated with D. pteronyssinus, although cytokine
      synthesis patterns were similar. CD8+CD28 co-cultures with PBMC showed greater
      proliferation than CD8+CD28+ T cell co-cultures, but cytokine synthesis patterns
      were not different. CONCLUSIONS: Our data confirm phenotypic and functional
      differences between CD28+ and CD28 T cells, irrespective of atopic status.
      Purified human CD8+CD28 T cells, freshly isolated from peripheral blood, do not
      have suppressor properties on allergen-specific proliferation or on cytokine
      synthesis in PBMC.

PMID- 17173840
TI  - Pharmacovigilance study of a regional intravenous immunoglobulin (II): evaluation
      and comparison of an improved pharmaceutical form.
AB  - INTRODUCTION: Intravenous immunoglobulin (IVIG) therapy is an effective treatment
      in patients with different diseases. This product must comply with all the
      regulatory requirements established by the World Health Organization and the
      European Pharmacopoeia for clinical tolerance, therapeutic efficacy, and viral
      safety. Although IVIG are effective and safe products, in some patients they may
      cause adverse reactions. OBJECTIVES: The aim of this study was to assess the
      clinical tolerance of two pharmaceutical forms (lyophilized and liquid) of
      Imunoglobulina G Endovenosa UNC (IVIG UNC), a regional IVIG preparation, and to
      compare the reported data. PATIENTS AND METHODS: The pharmacovigilance reports of
      149 infusions in 51 patients treated with lyophilized IVIG UNC and of 157
      infusions in 53 patients treated with liquid IVIG UNC were statistically
      evaluated. Clinical tolerance was evaluated through the adverse reactions
      reported. RESULTS: Lyophilized IVIG UNC: adverse reactions were reported in 6.7 %
      of the total number of infusions. Of these reactions, 4.0 % were mild, 2.0 % were
      moderate, and 0.7 % severe. Liquid IVIG UNC: adverse reactions were reported in
      3.2 % of the total number of infusions; of these, 1.3 % were mild, 1.9 % were
      moderate, and 0.0 % were severe. Statistical analysis showed no association
      between tolerance and the pharmaceutical form used (p > 0.05) and indicated
      similar tolerance for both preparations. CONCLUSIONS: Based on the results
      obtained, the excellent clinical tolerance of both pharmaceutical forms of IVIG
      UNC can be confirmed.

PMID- 17173841
TI  - Medical audit on asthma in an emergency department.
AB  - BACKGROUND: To determine the management of acute bronchial asthma in an adult
      emergency department. METHODS: A retrospective medical audit of 46 consecutive
      adult patients with acute asthma exacerbations was performed. We collected
      information from 48 episodes of acute asthma over a 5-month period. Using
      classical audit methodology, four indicators were examined: severity evaluation,
      diagnostic tests, specific treatment, and discharge treatment plans. RESULTS: The
      least recorded severity indicators were respiratory rate (27 %), heart rate (50
      %) and peak expiratory flow (20 %). Heart and respiratory auscultation were
      recorded in all patients and oxygen saturation was recorded in 93 %. Laboratory
      blood test and chest radiograph were performed in all patients. Arterial blood
      gas was tested in 57 %, electrocardiography in 17 %, and coagulation in 39 %. No
      treatment was provided in 12 % of patients. Bronchodilator medications were
      administered in all treated patients and oxygen was prescribed in 60 %. Systemic
      corticosteroids (methylprednisolone or hydrocortisone) were administered in 80 %
      of treated patients. Seventeen percent of patients were discharged from hospital
      with no change to their usual treatment. CONCLUSIONS: The following weak points
      were identified: 1) Severity assessment is inadequate, 2) use of diagnostic tests
      is excessive, 3) patients discharged to home with no treatment plan.
      Opportunities for improvement consisted of: 1) greater availability of peak
      expiratory flow meters, 2) individualized use of diagnostic tests, and 3)
      management protocols.

PMID- 17173842
TI  - Proposal for relative units of value (RUV) for use in allergy examinations.
AB  - Health resources are limited and consequently real cost generators must be
      identified to optimize resources. In the present article, we describe the
      structure of the Homogeneous Functional Groups (HFG) for Diagnostic Techniques in
      the Allergy Department of the Virgen de la Arrixaca University Hospital in Murcia
      (Spain) and the healthcare products generated. Based on the 2005 budget, variable
      costing was used to calculate the costs of the healthcare products generated
      (skin tests, investigation of drug allergies, etc.) by one of the three HFG (the
      HFG for complementary investigations). On the basis of these costs, and taking as
      the unit the cost of one skin prick test, we assigned relative units of value
      (RUV) to each of the products in our services portfolio. The following
      conclusions can be drawn: 1) the current system of variable costing provides
      information, which should be useful to health professionals; 2) the real cost
      generators in the microcosm of daily clinical practice should be identified to
      allow resource reallocation; 3) the costing system used enables modifications to
      be made that allow decision making on optimal use of the budget; 4) to take the
      decisions required to optimize resources, clinical management and complementary
      tests should go hand-in-hand.

PMID- 17173843
TI  - The natural course of atopy determined by skin prick tests in patients with
      bronchial asthma and/or rhinitis.
AB  - BACKGROUND: The skin prick test (SPT) is the cheapest, most widely used and
      practical method for the diagnosis of allergic diseases. The results of repeat
      test might show variations due to aging. OBJECTIVE: To perform repeat SPTs to
      determine possible changes in the atopy rate in general as well as changes in the
      allergen spectrum of atopic patients occurring over time and to identify the
      factors that could affect this change. METHODS: A total of 222 patients who
      received a diagnosis of bronchial asthma and/or persistent rhinitis in our Adult
      Allergy Unit and who attended follow-up visits in the outpatient unit over a 2
      year period were enrolled. SPT with 10 visit common aeroallergens were performed
      at the first and the second test was performed after an interval of at least 2
      years. RESULTS: The mean age was 36.4 +/- 11.4 years and 77.5 % of the patients
      were women. The mean interval between the two tests was 43.4 +/- 20.0 (minimum =
      24-maximum = 105) months. Repeat tests showed that the atopy rate decreased from
      58.6 % to 47.7 %; sensitivity rates to 10 allergens also decreased. These
      differences were statistically significant (p <0.05). CONCLUSION: The atopy rate
      determined by SPTs tends to decrease over time. The most important factor
      affecting this decrease is time itself.

PMID- 17173844
TI  - Common variable immunodeficiency. Old questions are getting clearer.
AB  - Common variable immunodeficiency (CVID) is a heterogeneous entity characterized
      by an impaired ability to produce antibodies. The failure is localized in
      partially mature B lymphocytes, though T lymphocyte abnormalities are
      occasionally present. This deficiency affects antibody synthesis and class switch
      from IgD and IgM, to IgG and IgA. CVID is related to selective IgA deficiency,
      and both abnormalities may coincide in one same family, and evolve from one to
      another in the same patient. The symptoms generally manifest in adults, but can
      occur at any age, even in infancy. Recurrent bacterial infections or pneumonias
      are frequent, and may be complicated by gastrointestinal problems, granulomas,
      autoimmune disorders or malignancies. A defect in memory B cells seems to
      condition the clinical severity. Recently, several mutations in genes encoding
      for molecules (CD19, TACI, ICOS) involved in B cell survival and isotype switch
      have been identified in patients with CVID. Nevertheless, genetic abnormalities
      have been found in less than 25 % of cases with CVID; the underlying mechanism
      thus remains unknown in the majority of CVID patients, and research in this field
      must continue.

PMID- 17173845
TI  - Childhood tuberculosis diagnosed and managed as asthma: case report.
AB  - The worldwide incidence of tuberculosis (TB) has been increasing. Although its
      diagnosis is well established in adults, in children it is difficult due to its
      particular aspects. We report a 3 years and 8 month-old infant who experienced
      chronic wheezing, classified as moderate-to-severe asthma, had recurrent
      pneumonia, and was not responsive to management with beta adrenergic agents.
      Chest X-rays (CXR) showed heterogeneous condensation in medium lobe and the chest
      computerized-tomography scan (CCT) a heterogeneous increase in pulmonary
      transparency, like condensation in the same lobe. After four months of treatment
      with anti tuberculosis agents, a significant improvement in symptoms, normal CXR,
      absence of pulmonary medium lobe condensation, and persistence fibro-atelectatic
      band in lingula were observed.

PMID- 17173847
TI  - Continued efficacy of sulfadoxine-pyrimethamine as second line treatment for
      malaria in children in Guinea-Bissau.
AB  - BACKGROUND: Sulfadoxine-pyrimethamine (S/P) is widely used for treatment of
      failures following the first line treatment for malaria in Africa. In Guinea
      Bissau, it has been recommended as second line therapy by the National Malaria
      Programme since 1996. In order to monitor any change of the in vivo sensitivity,
      the efficacy of S/P was studied immediately before the introduction of the drug
      and 6-9 years later. METHODS: Children participating in clinical in vivo studies
      were given S/P if having late clinical treatment failure following the treatment
      with quinine, chloroquine, or amodiaquine. Parasitological and clinical failures
      were evaluated during a 35-day follow-up. During the first study period whole
      blood sulfadoxine concentrations were measured on day 7. RESULTS: Altogether, 56
      children failed the initial treatment and were included in 1995/1996 as well as
      55 children in 2002/2004. The PCR-uncorrected adequate clinical and
      parasitological response rates on day 28 were 94% and 91%, and on day 35 they
      were 89% and 91%, respectively, in the two periods. No difference between median
      blood drug concentration in children with and without treatment failure was
      observed. INTERPRETATION: The efficacy of S/P as second line treatment for
      uncomplicated malaria has remained unchanged in spite of a relatively high level
      of genetic markers associated with Plasmodium falciparum resistance to S/P
      previously found in the area.

PMID- 17173848
TI  - High-resolution magnetic resonance imaging of the extraocular muscles and nerves
      demonstrates various etiologies of third nerve palsy.
AB  - PURPOSE: The etiology of third nerve palsy is usually diagnosed by history,
      motility examination, and presence of lid and pupil involvement, as well as
      cranial and vascular imaging. We used high-resolution magnetic resonance imaging
      (hrMRI) of the oculomotor nerve and affected extraocular muscles (EOMs) to
      investigate oculomotor palsy. DESIGN: Prospective, noncomparative, observational
      case series in an academic referral setting. METHODS: Twelve patients with
      nonaneurysmal oculomotor palsy of 0.75 to 252 months' duration were studied. In
      the orbit and along the intracranial oculomotor nerve, hrMRI at 1- to 2-mm
      thickness was performed. Coronal plane images of each orbit were obtained in
      multiple, controlled gaze positions. Structural abnormalities of the oculomotor
      nerve and associated changes in EOM volume and contractility were evaluated.
      RESULTS: Cases were categorized as tumor related, congenital, diabetic,
      traumatic, and idiopathic according to clinical characteristics and hrMRI
      findings. Reduction of volume and contractility of affected EOMs were noted in
      six patients; however, there was no marked EOMs atrophy in two cases of diabetic
      oculomotor palsy, and there were four cases of aberrant regeneration. hrMRI
      demonstrated the oculomotor nerve at the midbrain and at EOMs in all cases, and
      in two cases with previous normal neuroimaging elsewhere that demonstrated
      contrast-enhancing tumors on the oculomotor nerve. One patient with apparently
      unilateral congenital inferior division oculomotor palsy had no detectable
      ipsilateral and a hypoplastic contralateral oculomotor nerve exiting the
      midbrain. CONCLUSIONS: hrMRI provides valuable information in patients with
      oculomotor palsy, such as structural abnormalities of the orbit and oculomotor
      nerve, and atrophy and diminished contractility of innervated EOMs. This
      information could be helpful in diagnosis and management of oculomotor palsy.

PMID- 17173849
TI  - Vascularization is more delayed in amniotic membrane graft than conjunctival
      autograft after pterygium excision.
AB  - PURPOSE: To monitor the development of graft vascularization by indocyanine green
      angiography (ICGA) after pterygium excision with limbal-conjunctival autograft
      transplantation (LCAT) and amniotic membrane transplantation (AMT). DESIGN:
      Randomized prospective interventional case series. METHODS: Anterior segment ICGA
      findings at one, seven, and 30 days after surgery were evaluated in eyes with
      primary pterygium treated by excision and LCAT (14 eyes of 14 patients) or AMT
      (13 eyes of 13 patients), and the results for graft vascularization were
      compared. RESULTS: All conjunctival autografts showed early vascularization from
      underlying episcleral vascular bed as multiple hyperfluorescent foci at the graft
      margin on postoperative day 7; graft vascularization was complete on
      postoperative day 30. In contrast, all grafts in AMT group showed no graft
      vascularization at any stage after pterygium surgery. This delay of
      vascularization with AMT persisted until one month after surgery. CONCLUSIONS:
      Anterior segment ICGA is useful to monitor graft vascularization after pterygium
      surgery. Graft health after LCAT may be demonstrated by early graft
      vascularization and perfusion; however, there is a delay in graft vascularization
      after AMT that may be related to the antiangiogenic effects of the membrane.
      Further study is needed to demonstrate the relationship between this delay of
      graft perfusion and early postoperative pterygium recurrence.

PMID- 17173850
TI  - PACAP induces neurite outgrowth in cultured trigeminal ganglion cells and
      recovery of corneal sensitivity after flap surgery in rabbits.
AB  - PURPOSE: To evaluate the ability of pituitary adenylate cyclase-activating
      polypeptide (PACAP) to induce growth of neuronal processes in cultured trigeminal
      ganglion cells, and to accelerate neurite outgrowth and recovery of corneal
      sensitivity after creation of a corneal flap in a rabbit model of laser-assisted
      in situ keratomileusis (LASIK) surgery. DESIGN: Animal study. METHODS: The cDNA
      of rabbit PACAP was sequenced, and the expression of PACAP receptors in the
      trigeminal ganglia from rabbits was quantified by quantitative real-time
      polymerase chain reaction. Trigeminal ganglion cells were isolated from rabbits
      and cultured for 48 hours with or without PACAP27 (bioactive N-terminal peptide
      from PACAP). Cells were stained with antibody against neurofilaments, and neurite
      outgrowth was quantified by cell counting. In the rabbit LASIK model, a corneal
      flap with a planned thickness of 130 microm and 8.5 mm diameter was created with
      a microkeratome. The rabbits then received eyedrops containing PACAP27 four times
      a day for eight weeks, and corneal sensitivity was measured. Neurite outgrowth
      was assessed by staining histologic sections of the flap area for cholinesterase.
      RESULTS: The deduced amino acid sequence of PACAP in rabbit was identical to that
      of human. PACAP receptor, PAC1, was highly expressed in trigeminal ganglia from
      newborn and adult rabbits. PACAP27 at 1 microM induced growth of neuronal
      processes in cultured primary trigeminal ganglion cells. In the LASIK model,
      extensions of neuronal processes from amputated nerve trunks in cornea were
      observed after administration of eyedrops containing 1 or 10 microM PACAP27. The
      10 microM PACAP27 treatment also greatly accelerated recovery of corneal
      sensitivity. CONCLUSIONS: PACAP may be a candidate drug for ameliorating dry eye
      after LASIK surgery.

PMID- 17173851
TI  - Inexpensive chemifluorescent detection of antibody-alkaline phosphatase
      conjugates on Western blots using 4-methylumbelliferyl phosphate.

PMID- 17173852
TI  - SmaI cloning with regeneration of the SmaI site for sequential PCR product
      cloning.

PMID- 17173854
TI  - The properties of Bacillus cereus hemolysin II pores depend on environmental
      conditions.
AB  - Hemolysin II (HlyII), one of several cytolytic proteins encoded by the
      opportunistic human pathogen Bacillus cereus, is a member of the family of
      oligomeric beta-barrel pore-forming toxins. This work has studied the pore
      forming properties of HlyII using a number of biochemical and biophysical
      approaches. According to electron microscopy, HlyII protein interacts with
      liposomes to form ordered heptamer-like macromolecular assemblies with an inner
      pore diameter of 1.5-2 nm and an outer diameter of 6-8 nm. This is consistent
      with inner pore diameter obtained from osmotic protection assay. According to the
      3D model obtained, seven HlyII monomers might form a pore, the outer size of
      which has been estimated to be slightly larger than by the other method, with an
      inner diameter changing from 1 to 4 nm along the channel length. The hemolysis
      rate has been found to be temperature-dependent, with an explicit lag at lower
      temperatures. Temperature jump experiments have indicated the pore structures
      formed at 37 degrees C and 4 degrees C to be different. The channels formed by
      HlyII are anion-selective in lipid bilayers and show a rising conductance as the
      salt concentration increases. The results presented show for the first time that
      at high salt concentration HlyII pores demonstrate voltage-induced gating
      observed at low negative potentials. Taken together we have found that the
      membrane-binding properties of hemolysin II as well as the properties of its
      pores strongly depend on environmental conditions. The study of the properties
      together with structural modeling allows a better understanding of channel
      functioning.

PMID- 17173856
TI  - Molecular studies of the gel to liquid-crystalline phase transition for fully
      hydrated DPPC and DPPE bilayers.
AB  - Molecular dynamics simulations were used for a comprehensive study of the
      structural properties of saturated lipid bilayers, DPPC and DPPE, near the main
      phase transition. Though the chemical structure of DPPC and DPPE are largely
      similar (they only differ in the choline and ethanolamine groups), their
      transformation process from a gel to a liquid-crystalline state is contrasting.
      For DPPC, three distinct structures can be identified relative to the melting
      temperature (Tm): below Tm with "mixed" domains consisting of lipids that are
      tilted with partial overlap of the lipid tails between leaflet; near Tm with a
      slight increase in the average area per lipid, resulting in a rearrangement of
      the lipid tails and an increase in the bilayer thickness; and above Tm with
      unhindered lipid tails in random motion resulting in an increase in %gauche
      formed and increase in the level of interdigitation between lipid leaflets. For
      DPPE, the structures identified were below Tm with "ordered" domains consisting
      of slightly tilted lipid tails and non-overlapping lipid tails between leaflets,
      near Tm with minimal rearrangement of the lipids as the bilayer thickness reduces
      slightly with increasing temperature, and above Tm with unhindered lipid tails as
      that for DPPC. For DPPE, most of the lipid tails do not overlap as observed to
      DPPC, which is due to the tight packing of the DPPE molecules. The non
      overlapping behavior of DPPE above Tm is confirmed from the density profile of
      the terminal carbon atoms in each leaflet, which shows a narrow distribution near
      the center of the bilayer core. This study also demonstrates that atomistic
      simulations are capable of capturing the phase transition behavior of lipid
      bilayers, providing a rich set of molecular and structural information at and
      near the transition state.

PMID- 17173855
TI  - Seven transmembrane receptors: a brief personal retrospective.
AB  - Receptors have fascinated biologists for more than a century and they have
      fascinated me for the entirety of my own research career. The seven transmembrane
      receptors, also known as G protein coupled receptors, represent the largest of
      the several families of plasma membrane receptors, comprising more than a
      thousand genes and regulating virtually all known physiological processes in
      mammals. Moreover, they represent one of the commonest targets of currently used
      drugs. I have spent the entirety of my research career working on these
      receptors. Here I set down some personal reflections on the evolution of the
      field during the past 35 years, hanging the thread of the story on some of the
      work from my own laboratory.

PMID- 17173853
TI  - Quantitative continuous assay for hyaluronan synthase.
AB  - A rapid, continuous, and convenient three-enzyme coupled UV absorption assay was
      developed to quantitate the glucuronic acid and N-acetylglucosamine transferase
      activities of hyaluronan synthase from Pasteurella multocida (PmHAS). Activity
      was measured by coupling the UDP produced from the PmHAS-catalyzed transfer of
      UDP-GlcNAc and UDP-GlcUA to a hyaluronic acid tetrasaccharide primer with the
      oxidation of NADH. Using a fluorescently labeled primer, the products were
      characterized by gel electrophoresis. Our results show that a truncated soluble
      form of recombinant PmHAS (residues 1-703) can catalyze the glycosyl transfers in
      a time- and concentration-dependent manner. The assay can be used to determine
      kinetic parameters, inhibition constants, and mechanistic aspects of this enzyme.
      In addition, it can be used to quantify PmHAS during purification of the enzyme
      from culture media.

PMID- 17173857
TI  - STAT3 activation inhibits human bronchial epithelial cell apoptosis in response
      to cigarette smoke exposure.
AB  - We have previously reported that cigarette smoke can induce DNA damage in human
      lung cells without leading to apoptosis or necrosis. In this study, we report
      that STAT3 is required for the survival of human bronchial epithelial cells
      (HBECs) following cigarette smoke-induced DNA damage. Cigarette smoke extract
      (CSE) exposure increases STAT3 phosphorylation (Tyr 705) and DNA binding activity
      in HBECs. CSE also stimulates IL-6 release and mRNA expression. Anti-IL-6
      neutralizing antibody partially blocks STAT3 activation and renders the cells
      sensitive to CSE-induced DNA damage. Suppression of STAT3 by siRNA results in
      severe DNA damage and cell death in response to CSE exposure. These findings
      suggest that STAT3 mediates HBEC survival in response to CSE-induced DNA damage,
      at least in part, through the IL-6/STAT3 signaling pathway.

PMID- 17173858
TI  - Structural analysis of the 26S proteasome by cryoelectron tomography.
AB  - The 26S proteasome is the key enzyme of intracellular protein degradation in
      eukaryotic cells. It is a multisubunit complex of 2.5 MDa confining the
      proteolytic action to an inner compartment with tightly controlled access.
      Structural studies of this intriguing molecular machine have been hampered by its
      intrinsic instability and its dynamics. Here we have used an unconventional
      approach to obtain a three-dimensional structure of the holocomplex uncompromised
      by preparation-induced alterations and unbiased by any starting model. We have
      performed a tomographic reconstruction, followed by averaging over approx. 150
      individual reconstructions, of Drosophila 26S proteasomes suspended in a thin
      layer of amorphous ice.

PMID- 17173859
TI  - Interaction of HIPPI with putative promoter sequence of caspase-1 in vitro and in
      vivo.
AB  - To investigate the mechanism of increased expression of caspase-1 in Hippi
      expressing HeLa and Neuro 2A cells, reported earlier, we report here that HIPPI
      directly interacted with upstream sequence of caspase-1 gene (-700 to +17, 717
      bp). Deletion of this 717 bp sequence and further analysis by electrophoretic
      mobility shift assay and fluorescence quenching revealed that HIPPI interacted
      with 60 bp (-151 to -92) upstream sequence of caspase-1. We also observed by
      chromatin immunoprecipitation assay that HIPPI interacted with the 717 bp
      sequence in vivo. In luciferase assay, when expression of the reporter gene was
      driven by either 717 bp or 60 bp caspase-1 upstream sequences, luciferase
      activity was increased in GFP-Hippi expressing HeLa cells in comparison to that
      obtained with parental HeLa cells with the same constructs. Similar result was
      obtained in Neuro2A cells with 717 bp caspase-1 upstream sequence. In summary, we
      showed that HIPPI could interact with the putative promoter sequence of caspase-1
      and increased the expression of the downstream gene suggesting that HIPPI could
      act as transcription regulator.

PMID- 17173860
TI  - In vitro transformation of mesenchymal stem cells by oncogenic H-rasVal12.
AB  - Tissue stem cells may serve as progenitors for malignant tumors derived from the
      same tissue. Here, we report the establishment of immortalized human mesenchymal
      stem cells (ihMSC) and tested the feasibility of using ihMSC as presarcomatous
      cells. Immortalization was achieved by introducing the genes for human telomerase
      reverse transcriptase and Bmi1. ihMSC retained the potential for multi
      directional differentiation of the original MSC. To transform ihMSC, we
      introduced an oncogenic H-ras(Val12) gene, and established the cell line ihMSC
      ras. ihMSC-ras had the phenotype of fully transformed cells and retained
      adipogenic and chondrogenic, but not osteogenic, potential. Interestingly, ihMSC
      ras demonstrated morphological features of autophagy, and inhibition of the ERK
      pathway suppressed the production of autophagosomes, indicating that ras/ERK
      signaling is responsible for the induction of autophagy. Thus ihMSC will serve as
      a material with which to analyze the tumorigenic and differentiation-modifying
      effects of candidate oncogenes involved in the development of sarcomas.

PMID- 17173861
TI  - Fasciculation and elongation protein zeta-1 (FEZ1) participates in the
      polarization of hippocampal neuron by controlling the mitochondrial motility.
AB  - The fasciculation and elongation protein zeta-1 (FEZ1), a mammalian orthologue of
      Caenorhabditis elegans UNC-76 protein, is a 45-kDa protein with four coiled
      coiled domains and efficiently promotes the neurite elongation in the rat
      phaeochromocytoma PC12 cells. UNC-76 proteins of C. elegans and Drosophila have
      been genetically demonstrated to be involved in the axonal guidance. We here show
      that FEZ1 RNA interference (RNAi) represses the formation of axon in rat embryo
      hippocampal neurons. An anterograde mitochondrial movement is also retarded in
      neurites of the RNAi-treated hippocampal neurons. Moreover, the size of
      mitochondria is considerably elongated by the RNAi treatment. The transport of
      mitochondria from soma to axon or dendrites is essential for the neuronal
      differentiation. Therefore, our results strongly suggest that FEZ1 participates
      in the establishment of neuronal polarity by controlling the mitochondrial
      motility along axon.

PMID- 17173862
TI  - Concerning the dynamic instability of actin homolog ParM.
AB  - Using in vitro TIRF- and electron-microscopy, we reinvestigated the dynamics of
      native ParM, a prokaryotic DNA segregation protein and actin homolog. In contrast
      to a previous study, which used a cysteine ParM mutant, we find that the
      polymerization process of wild type ATP-ParM filaments consists of a
      polymerization phase and a subsequent steady state phase, which is dynamically
      unstable, like that of microtubules. We find that the apparent bidirectional
      polymerization of ParM, is not due to the intrinsic nature of this filament, but
      results from ParM forming randomly oriented bundles in the presence of crowding
      agents. Our results imply, that in the bacterium, ParM filaments spontaneously
      form bipolar bundles. Due to their intrinsic dynamic instability, ParM bundles
      can efficiently "search" the cytoplasmic lumen for DNA, bind it equally well at
      the bipolar ends and segregate it approximately symmetrically, by the insertion
      of ParM subunits at either end.

PMID- 17173863
TI  - GC content and genome length in Chargaff compliant genomes.
AB  - Musto et al. [H. Musto, H. Naya, A. Zavala, H. Romero, F. Alvarez-Valin, G.
      Bernardi, Genomic GC level, optimal growth temperature, and genome size in
      prokaryotes, Biochem. Biophys. Res. Commun. 347 (2006) 1-3] recently reported a
      linear correlation between GC content and genome length. The regression model was
      heteroscedactic which suggested that the relationship might be more clearly
      defined. Alternative regression models (R(2)>0.95) were fitted to a set of over
      900 sequences compliant with Chargaff's second parity rule. The new models
      suggest that the relationship between GC content and genome length is more
      complex than was originally suggested. While similar models can be derived for
      non-Chargaff compliant genomes, their interpretation is likely to be more
      difficult.

PMID- 17173864
TI  - Crystal structure of the Nod1 caspase activation and recruitment domain.
AB  - Nod-like receptors (NLRs), Nod1 and Nod2 are cytosolic detectors of pathogen
      associated molecular patterns (PAMPs). Nod1 is a three-domain protein, consisting
      of a caspase activation and recruitment domain (CARD), a nucleotide-binding
      oligomerization domain (NOD), and a leucine-rich repeat domain (LRR). The binding
      of PAMPs to the LRR results in the activation of signaling through homophilic
      CARD-CARD interactions. Several CARD structures have been determined, including a
      recent NMR structure of Nod1 CARD. In contrast to the reported NMR structure, the
      crystal structure reported here is a dimer, where the sixth helix is swapped
      between two monomers. While the overall structure is very similar to the known
      CARD structures, this is the first report of a homodimeric CARD structure. The
      ability of the CARD to exist in monomeric and dimeric forms suggests another
      level of regulation in the activation of NLR proteins.

PMID- 17173865
TI  - c-Jun induces apoptosis of starved BM2 monoblasts by activating cyclin A-CDK2.
AB  - c-Jun is one of the major components of the activating protein-1 (AP-1), the
      transcription factor that participates in regulation of proliferation,
      differentiation, and apoptosis. In this study, we explored functional
      interactions of the c-Jun protein with several regulators of the G1/S transition
      in serum-deprived v-myb-transformed chicken monoblasts BM2. We show that the c
      Jun protein induces expression of cyclin A, thus up-regulating activity of cyclin
      A-associated cyclin-dependent kinase 2 (CDK2), and causing massive programmed
      cell death of starved BM2cJUN cells. Specific inhibition of CDK2 suppresses
      frequency of apoptosis of BM2cJUN cells. We conclude that up-regulation of cyclin
      A expression and CDK2 activity can represent important link between the c-Jun
      protein, cell cycle machinery, and programmed cell death pathway in leukemic
      cells.

PMID- 17173866
TI  - NRSF regulates the developmental and hypertrophic changes of HCN4 transcription
      in rat cardiac myocytes.
AB  - The HCN4 channel shows differential expression patterns during the embryonic
      development and hypertrophy of hearts. Briefly, HCN4 expression is maximally
      activated in embryonic hearts and quickly diminishes after birth. However, it is
      reactivated during cardiac hypertrophy. The sequence analysis of HCN4 gene
      revealed the presence of a conserved NRSE motif, which is known to bind the
      transcriptional factor neuron-restrictive silencing factor (NRSF). A promoter
      analysis of HCN4 with rat cardiac myocytes identified the region inducing a basal
      transcriptional activity. This region drove a high activity in embryonic
      myocytes, but not in neonatal myocytes treated with hypertrophic agents. After
      confirming that NRSF protein binds to the NRSE, HCN4 promoter activities modified
      by NRSE were evaluated. With wild-type NRSE, the promoter activity correlated
      well with the developmental and hypertrophic changes of HCN4 expression, whereas
      mutant NRSE constructs failed. We conclude that the NRSE-NRSF system was
      implicated in HCN4 expression in cardiac myocytes.

PMID- 17173868
TI  - Neural correlates of semantic priming for ambiguous words: an event-related fMRI
      study.
AB  - We investigated the neural correlates of semantic priming by using event-related
      fMRI to record blood oxygen level dependent (BOLD) responses while participants
      performed speeded lexical decisions (word/nonword) on visually presented related
      versus unrelated prime-target pairs. A long stimulus onset asynchrony of 1000 ms
      was employed, which allowed for increased controlled processing and selective
      frequency-based ambiguity priming. Conditions included an ambiguous word prime
      (e.g. bank) and a target related to its dominant (e.g. money) or subordinate
      meaning (e.g. river). Compared to an unrelated condition, primed dominant targets
      were associated with increased activity in the LIFG, the right anterior cingulate
      and superior temporal gyrus, suggesting postlexical semantic integrative
      mechanisms, while increased right supramarginal activity for the unrelated
      condition was consistent with expectancy based priming. Subordinate targets were
      not primed and were associated with reduced activity primarily in
      occipitotemporal regions associated with word recognition, which may be
      consistent with frequency-based meaning suppression. These findings provide new
      insights into the neural substrates of semantic priming and the functional
      anatomic correlates of lexical ambiguity suppression mechanisms.

PMID- 17173867
TI  - An ERP study of syntactic processing in English and nonsense sentences.
AB  - The timecourse of the interaction between syntactic and semantic information
      during sentence processing in monolingual native English speakers was
      investigated using event-related potentials (ERPs). To examine the effects of
      semantic information on syntactic processing, the results for normal English
      sentences were compared to those for semantically impoverished nonsense
      (Jabberwocky) sentences. Within each sentence type condition, half of the
      sentences contained a syntactic violation. Violations elicited a larger amplitude
      N1 and more negative ERPs around 200 ms after the onset of the critical word
      relative to the grammatical condition. Although these effects were observed in
      both sentence types, they were anteriorly distributed for English sentences only.
      Moreover, the P600 elicited by the syntactic violation was attenuated in
      processing Jabberwocky as compared to English sentences. These results suggest
      that semantic and syntactic information are integrated during the earlier stages
      of syntactic processing indexed by the anterior negativities, and that these
      interactions continue in the later stages of processing indexed by the P600.

PMID- 17173869
TI  - Medial versus lateral prefrontal dissociation in movement selection and
      inhibitory control.
AB  - We aimed to test the hypothesis that the cerebral selection of movement includes
      active suppression of unwanted movements. To that end, a cerebral activation
      paradigm was used in which index finger flexion was compared with similar
      movement, made together with fingers 3, 4, 5. Cerebral activations were assessed
      by positron emission tomography (PET) measurements of cerebral perfusion in 10
      healthy subjects, during the two motor tasks and rest. Statistical parametric
      mapping (SPM) revealed significant increase of (antero)medial prefrontal activity
      and subtle changes in pallidum and thalamus in the condition of less movement,
      i.e. isolated index finger flexion contrasted to full-hand flexion. These
      increases indicated a mechanism of selection mediated by active suppression of
      unwanted movements. Suppression of all motor responses was inferred from
      anterolateral prefrontal activation related to rest (with only auditory cues),
      contrasted to both motor conditions. This segregation of inhibitory functions
      specifies the complementary character of response selection and inhibitory
      control, in such a way, that towards the medial prefrontal surface, a transition
      from general to increasingly selective inhibition allows the internal ordering of
      action.

PMID- 17173870
TI  - Acupuncture inhibits microglial activation and inflammatory events in the MPTP
      induced mouse model.
AB  - Using a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced Parkinson's disease (PD), this study investigated on the neuroprotective
      effects of acupuncture by examining whether acupuncture contributed to inhibiting
      microglial activation and inflammatory events. C57BL/6 mice were treated with
      MPTP (30 mg/kg, i.p.) for 5 consecutive days. Acupuncture was then applied to
      acupoints Yanglingquan (GB34) and Taichong (LR3) starting 2 h after the first
      MPTP administration and then at 48 h intervals until the mice were sacrificed for
      analyses at 1, 3, and 7 days after the last MPTP injection. These experiments
      demonstrated that acupuncture inhibited the decreased of the tyrosine hydroxylase
      (TH) immunoreactivity (IR) and generated a neuroprotective effects in the
      striatum (ST) and the substantia nigra (SN) on days 1, 3, and 7 post-MPTP
      injections. Acupuncture attenuated the increase of macrophage antigen complex-1
      (MAC-1), a marker of microglial activation, at 1 and 3 days and reduced the
      increases in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS)
      expression on days 1, 3, and 7. In MPTP group, striatal dopamine (DA) was
      measured by 46% at 7 days, whereas DA in the acupuncture group was 78%. On the
      basis of these results, we suggest that acupuncture could be used as a
      neuroprotective intervention for the purpose of inhibiting microglial activation
      and inflammatory events in PD.

PMID- 17173871
TI  - Inhibitory effect of taurine on veratridine-evoked D-[3H]aspartate release from
      murine corticostriatal slices: involvement of chloride channels and mitochondria.
AB  - We have previously shown that the inhibitory neuromodulator taurine attenuates
      the release of preloaded D-[3H]aspartate from murine corticostriatal slices
      evoked by ischemic conditions or by application of the sodium channel agonist
      veratridine. The release of D-[3H]aspartate (a non-metabolized analog of
      glutamate) was used as an index of glutamate release. The aim of the present
      study was to reveal the molecular mechanisms responsible for this inhibitory
      effect of taurine. It was shown that 10 mM taurine suppresses D-[3H]aspartate
      release evoked by 0.1 mM veratridine, but does not affect the high-K+ -(50 mM) or
      ouabain- (0.1 mM) evoked release. Taurine had no effect in Ca2+ -free medium when
      the synaptic exocytosis of D-[3H]aspartate was inhibited. Nor did it suppress the
      release from slices preloaded with the competitive glutamate uptake blocker DL
      threo-beta-hydroxyaspartate (THBA), which inhibits D-[3H]aspartate release
      mediated by the reverse action of glutamate transporters. Omission of Cl- from
      the incubation medium reduced the effect of taurine, signifying the involvement
      of a Cl- channel. The glycine receptor antagonist strychnine and the GABA(A)
      receptor antagonist bicuculline did not block the taurine effect, although
      picrotoxin, a less specific blocker of agonist-gated chloride channels,
      completely prevented the effect of taurine on veratridine-induced D-[3H]aspartate
      release. The respiratory chain blocker rotenone or mitochondrial protonophore
      carbonyl cyanide 3-chlorophenylhydrazone (CCCP) in combination with the
      mitochondrial ATPase inhibitor oligomycin, which inhibits the mitochondrial Ca2+
      uniporter, also reduced the effect of taurine. The results obtained in the
      present study show that taurine acts specifically on the release of preloaded D
      [3H]aspartate evoked by veratridine, but not on that evoked by other depolarizing
      agents, and affects the release mediated both by synaptic exocytosis and the
      reverse action of glutamate transporter. Taurine may attenuate D-[3H]aspartate
      release by regulation of mitochondrial Ca2+ sequestration and by activation of a
      chloride channel, but not that governed by GABA(A) or strychnine-sensitive
      glycine receptors.

PMID- 17173872
TI  - Altered tactile spatial attention in the early blind.
AB  - To investigate whether superior tactile acuity in the blind is due to alterations
      of attentional selection mechanisms, event-related brain potentials (ERPs) were
      measured in a group of early blind and a group of sighted individuals who
      performed a difficult tactile spatial selection task. We found systematic
      differences in the attentional processing of tactile events between early blind
      and sighted individuals. The blind not only responded faster to tactile targets,
      but also showed attentional modulations of early somatosensory ERP components
      (P100 and N140). In contrast, ERP effects of spatial attention in the sighted
      only emerged at longer-latencies (about 200 ms post-stimulus). Our findings
      suggest that increased use of one sense due to sensory deprivation, such as touch
      in blind people, leads to alterations of attentional selection mechanism within
      modality-specific cortex.

PMID- 17173873
TI  - The temporal profile of genomic responses and protein synthesis in ischemic
      tolerance of the rat brain induced by repeated hyperbaric oxygen.
AB  - Repeated hyperbaric oxygen (HBO) exposure prior to ischemia has been reported to
      provide neuroprotection against ischemic brain injury. The present study examined
      the time course of neuroprotection of HBO (3.5 atmosphere absolute, 100% oxygen,
      1 h for 5 consecutive days) and the changes of gene/protein expression in rats.
      First, at 6 h, 12 h, 24 h, and 72 h after HBO sessions, rats were subjected to
      forebrain ischemia (8 min). Histopathological examination of hippocampal CA1
      neurons was done 7 days after ischemia. Second, temporal genomic responses and
      protein expression were examined at the same time points after HBO sessions
      without subjecting animals to ischemia. HBO significantly reduced loss of
      hippocampal CA1 neurons that normally follows transient forebrain ischemia when
      the last HBO session was 6 h, 12 h, or 24 h before ischemia (survived neurons
      55%, 75%, and 53%, respectively), whereas if there was a 72-h delay before the
      ischemic insult, HBO was not protective (survived neurons only 6%). Statistical
      analysis on microarray data showed significant upregulation in 60 probe sets
      including 7 annotated genes (p75NTR, C/EBPdelta, CD74, Edg2, Trip10, Nrp1, and
      Igf2), whose time course expressions corresponded to HBO-induced neuroprotection.
      The protein levels of p75NTR, C/EBPdelta, and CD74 were significantly increased
      (maximum fold changes 2.9, 2.0, and 7.9, respectively). The results suggest that
      HBO-induced neuroprotection against ischemic injury has time window, protective
      at 6 h, 12 h and 24 h but not protective at 72 h. Although the precise
      interaction is to be determined, the genes/proteins relevant to neurotrophin and
      inflammatory-immune system may be involved in HBO-induced neuroprotection.

PMID- 17173874
TI  - Impact of an intense stress on ethanol consumption in female rats characterized
      by their pre-stress preference: modulation by prenatal stress.
AB  - We examined the influence of prenatal stress on alcohol preference in adult
      female rats exposed to an intense stress. To take into account interindividual
      variability, the study was conducted in animals categorized as low or high
      alcohol preferring. After footshock, control high-preferring rats strongly
      reduced their alcohol consumption; in contrast, alcohol consumption was not
      changed in high-preferring rats that were prenatally stressed.

PMID- 17173875
TI  - Quantitative measurement of neurological deficit after mild (30 min) transient
      middle cerebral artery occlusion in rats.
AB  - Although 30-min transient middle cerebral artery occlusion (30-min tMCAo) causes
      reproducible subcortical infarction in rats, it is difficult to evaluate the
      resulting neurological deficit using common behavioral tests such as the rota-rod
      test, adhesive-removal test, or narrow beam test. Establishment of a method of
      quantitative evaluation would help to develop a novel therapeutic approach to
      treat cerebral infarction. To solve this problem, we examined whether the
      neurological deficit could be detected by the Montoya staircase test or
      methamphetamine-induced rotation, which are commonly used in a Parkinson disease
      model induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). From 10
      to 14 days after tMCAo, the Montoya staircase test showed significant clumsiness
      in forelimb tasks contralateral to the lesion side, whereas sham-operated rats
      showed no significant clumsiness in both forelimbs. The number of ipsilateral
      rotations induced by methamphetamine was also increased in tMCAo-rats at 21 days
      after tMCAo. Although Pearson's correlations coefficient showed that the results
      of these tests were correlated with the infarction volume, there was no
      significant correlation between the results of these two tests. These findings
      imply that the neurological deficit detected by both tests might reflect the
      severity of ischemic injury, but each test might evaluate different aspects of
      neurological deficit. Thus, the Montoya staircase test and methamphetamine
      induced rotation are useful to evaluate neurological deficit in the chronic stage
      of subcortical infarction induced by 30-min tMCAo.

PMID- 17173876
TI  - The neural correlates of attention orienting in visuospatial working memory for
      detecting feature and conjunction changes.
AB  - The neural mechanisms of attentional orienting in visuospatial working memory for
      change detection were investigated. A spatial cue was provided with the onset
      time manipulated to allow more effective top-down control with an early cue than
      with a late cue. The change type was also manipulated so that accurate detection
      depended on color or the binding of color and location. The results showed that
      both the frontal and parietal regions subserved the change detection task without
      cueing. When data were collapsed over the two change types, early cueing
      increased activation in the right inferior frontal gyrus (IFG) and middle frontal
      gyrus (MFG) while late cueing increased activation in the right inferior parietal
      lobule (IPL) and temporoparietal junction (TPJ) as compared with the no-cue
      condition. The cue onset time led to different levels of enhancement in the
      frontal and posterior cortices related to top-down control and stimulus-driven
      orienting. For feature detection, early cueing increased activation in the right
      MFG and late cueing increased activation in the bilateral precuneus (PCu), right
      TPJ, and right cuneus. The neural correlates of conjunction detection involved
      the right PCu and cerebellum without cueing, were associated with the anterior
      MFG, left IFG, and the left STG with early cueing, and involved the right MFG,
      left IFG, and right IPL with late cueing. The left IFG was correlated with memory
      retrieval of the cued representation for conjunction detection, and the right
      posterior PCu was associated with maintenance and memory retrieval among
      competing stimuli.

PMID- 17173877
TI  - The superficial layers of the superior colliculus are cytoarchitectually and
      myeloarchitectually disorganized in the reelin-deficient mouse, reeler.
AB  - The causative gene for the reeler mouse is reelin which encodes Reelin protein,
      an extracellular molecule. In the present study, we have examined the
      cytoarchitecture, myeloarchitecture, and afferent/efferent systems of the
      superior colliculus (SC) of the reeler mouse. In the reeler, the laminar
      structures of the superficial three layers of the SC were disorganized and
      intermingled into a single layer, i.e., the superficial fused layer (SuF), as
      previously reported in the reelin-deficient SRK rat (Sakakibara et al., Develop.
      Brain Res. 141:1-13). Next, we have investigated the course and terminals of
      visual corticotectal and retinotectal projections with an injection of biocytin
      into the visual cortex or an injection of cholera toxin subunit B into the
      retina, respectively. In the reeler, anterogradely labeled visual corticotectal
      and retinotectal fibers took an aberrant course within the SuF, resulting in
      abnormal myeloarchitecture of the superficial SC of the reeler. Retrograde
      labeling of tectospinal tract neurons could not show any differences between the
      normal and reeler mice, suggesting that the deep layers of the reeler SC are
      cytoarchitectually normal. In situ hybridization and immunohistochemical studies
      have shown that reelin mRNA and Reelin protein were both recognized in the normal
      SC. These results suggest that Reelin protein plays some roles in histogenesis of
      the superficial layers of the SC.

PMID- 17173878
TI  - Simulated actions in the first and in the third person perspectives share common
      representations.
AB  - Normal subjects simulated a grasping action with two levels of difficulty of the
      grasp. In one condition, they simulated the movement from their own, first person
      perspective (1P). In the other condition, they simulated the same movement made
      by a person facing them (third person perspective 3P). The time to complete the
      movement was found to be closely similar in the two conditions. Furthermore, the
      same difference in simulation time between easy and difficult grasps was retained
      in the two conditions. These results show that a self-generated and an observed
      action share the same representation. This representation can be used from
      different perspectives.

PMID- 17173879
TI  - Synthesis of 3'-C-substituted thymidine derivatives by free-radical techniques:
      scope and limitations.
AB  - The scope and limitations of radical-mediated 3'-C-substitution of pyrimidine
      nucleosides was evaluated with 5'-O-(tert-butyldimethylsilyl)thymidine or its
      tert-butyldiphenylsilyl analogue having thionoester or thionoamide groups at O
      3', including (methylthio)thiocarbonyl, (phenoxy)thiocarbonyl,
      (pentafluorophenoxy)thiocarbonyl, and (1-imidazolyl)thiocarbonyl. Their reaction
      with acrylonitrile, methyl acrylate, and allyltributyltin under radical
      generating conditions affords corresponding 3'-C-alkylated products, together
      with the product of simple deoxygenation at C-3'. The conditions for optimizing
      the yield of 3'-C-substituted product are presented.

PMID- 17173880
TI  - Glycosylation in room temperature ionic liquid using unprotected and unactivated
      donors.
AB  - Glycosylation in room temperature ionic liquid is demonstrated using unprotected
      and unactivated donors. Modest yields of simple benzyl glycosides and
      disaccharides of glucose, mannose and N-acetylgalactosamine were obtained in 1
      ethyl-3-methylimidazolium benzoate with Amberlite IR-120 (H(+)) resin or p
      toluenesulfonic acid as promoters.

PMID- 17173881
TI  - Preparation of multifunctional glyconanoparticles as a platform for potential
      carbohydrate-based anticancer vaccines.
AB  - A novel platform for anticancer vaccines has been prepared using
      glyconanotechnology recently developed in our laboratory. Ten different
      multifunctional gold glyconanoparticles incorporating sialylTn and Lewis(y)
      antigens, T-cell helper peptides (TT) and glucose in well defined average
      proportions and with differing density have been synthesised in one step and
      characterised using NMR and TEM. Size and nature of the linker were crucial to
      control kinetics of S-Au bond formation and to achieve the desired ligand ratio
      on the gold clusters. The technology presented here opens the way for tailoring
      polyvalent anticancer vaccines candidates and drug delivery carriers with defined
      average chemical composition.

PMID- 17173882
TI  - Crystal structure and NMR spectroscopy of aldonamides derived from D-glycero-D
      gulo-heptono-1,4-lactone.
AB  - We report the preparation of 12 aldonamides derived from D-glycero-D-gulo-heptono
      1,4-lactone, their NMR characterization and study (13C, 1H, 15N NMR) in Me2SO-d6
      solution. The evaluation of the coupling constants 3JH,H has shown that the sugar
      chain conformation in solution is all-trans for the studied amides. Because some
      amides crystallized, we discussed the crystal packing and found motifs. The
      conformation of the amides in the crystal structures displays two sickles at C2
      and C3, with the exception of one that is all-trans. The bends cause the
      formation of the mean planes C1-C2-C3 and C3-C4-C5-C6-C7 with an average
      interplanar angle of 88 degrees. We found three main kinds of crystal packing
      depending on the N-substituent; head-to-tail, bilayer and pseudo-hexagonal mode,
      all the three show hydrogen-bonding networks that stabilize the crystal lattice.

PMID- 17173883
TI  - Tea polyphenols in preventing cardiovascular diseases.

PMID- 17173884
TI  - Palmitic acid in HDL is associated to low apo A-I fractional catabolic rates in
      vivo.
AB  - BACKGROUND: HDL becomes enriched with non-esterified fatty acids (NEFAs) in some
      pathologies, such as nephrotic syndrome, as well as after aerobic exercise.
      However, little is known about the impact of NEFAs on HDL metabolism. We
      investigated the effects of one NEFA, the palmitic acid, on HDL structure and
      catabolism. METHODS: HDL enrichment with palmitic acid (HDLPal) was performed by
      fusing phosphatidyl choline small unilamellar vesicles containing the NEFA with
      human HDL isolated from a pool of 5 normolipidemic plasma. HDL enriched only with
      phosphatidyl choline (HDLPhl) and native HDL (HDLCtrl) were included as controls.
      RESULTS: As expected, HDLPal surface charge density was higher than HDLPhl and
      HDLCtrl (2014.4+/-164.8 vs. 1682.7+/-149.5 and 1758.2+/-124.3-esu/cm2,
      respectively, p<0.05). Both, HDLPal and HDLPhl were better substrates for
      cholesteryl esters transfer protein (CETP) than HDLCtrl (% of transfer, 13.02+/
      3.8 and 12.7+/-4.5 vs. 7.8+/-2.7% in 16 h, respectively, p<0.05). HDLPal apo A-I
      catabolism in vivo, as performed in New Zealand white rabbits by exogenous
      radiolabeling, was markedly lower than that of HDLPhl and HDLCtrl (fractional
      catabolic rate, 0.019+/-0.008 vs. 0.030+/-0.005 and 0.047+/-0.003 h-1,
      respectively, p<0.001), suggesting that negative charge is inversely related to
      HDL-apo A-I catabolism. CONCLUSIONS: Enrichment with palmitic acid increases the
      negative electric charge of HDL at physiological pH, contributes to decrease
      their catabolism, and is associated to an enhanced lipid transfer by CETP that
      has been related to the atherogenic process.

PMID- 17173885
TI  - Prognostic significance of plasma resistin levels in patients with
      atherothrombotic ischemic stroke.
AB  - BACKGROUND: Resistin (RSN) is an adipocytokine involved in insulin resistance,
      obesity and atherosclerosis. This study aimed to investigate the association
      between plasma RSN and outcome after ischemic stroke. METHODS: RSN measured
      within 24 h after the event was related to functional outcome and 5-year survival
      in 211 subjects with first-ever atherothrombotic ischemic stroke. Prognosis was
      assessed by the Kaplan Meier and the Cox techniques. RESULTS: The probabilities
      of death were 80.4%, 46.2% and 15.7% (p<0.001) for patients stratified according
      to tertiles of RSN (>30 ng/mL, 20-30 ng/mL and<20 ng/mL, respectively). The
      proportion of dependency (modified Rankin Scale score>or=3) was greater in 5-year
      survivors with RSN in the upper tertile (6/11 [54.5%]) compared to the middle
      (20/56 [35.7%]) and the lowest tertile (8/43 [18.6%]; p<0.01). C-reactive protein
      levels (hazard ratio [HR] 3.96 [95% CI 2.06, 8.91]; p<0.001), coronary heart
      disease (2.69 [1.62, 6.23]; p<0.001), RSN levels (2.12 [1.31, 5.08] p<0.001),
      National Institute of Health Stroke Scale score (2.02 [1.23, 4.49]; p<0.01) and
      age (1.84 [1.19, 3.93]; p<0.01) were independent predictors of death.
      CONCLUSIONS: High plasma RSN appears to be associated with increased risk of 5
      year mortality or disability after atherothrombotic ischemic stroke,
      independently of other adverse predictors.

PMID- 17173886
TI  - Immunoglobulin glycation with fructose: a comparative study.
AB  - BACKGROUND: Immunoglobulins undergo non-enzymatic glycation reaction with sugars
      both in vivo and in vitro. Effects of glycation on the ability of the antibodies
      to bind antigens are contradictory. Antibodies raised in various animals may also
      be exposed to high concentration of sugars that are added during freeze
      drying/pasteurization for preservation. METHODS: IgG isolated from the sera of
      goat, human, rabbit, mouse, buffalo as well as IgY from hen egg yolk was
      subjected to in vitro glycation with fructose. The behavior of glycated IgG was
      investigated by SDS-PAGE, hyperchromicity at 280 nm, tryptophan fluorescence and
      new fluorescence. RESULTS: Marked variations were observed in the response of the
      immunoglobulins derived from various animals to incubation with fructose. Also,
      incubation of anti-glucoseoxidase (GOD) antibodies with fructose resulted in a
      rapid loss of their ability to bind the enzyme antigen as revealed by
      immunodiffusion and ELISA. DETAPAC and EDTA were quite protective but were unable
      to completely prevent the fructose-induced alterations. CONCLUSIONS:
      Immunoglobulins derived from goat, human, rabbit, mouse, buffalo and hen egg yolk
      undergo remarkable structural alterations on incubation with fructose. The
      susceptibility of the immunoglobulins to the modification however differed
      remarkably. The goat IgG was most recalcitrant while hen egg yolk IgY was most
      susceptible to the alterations. DETAPAC or EDTA restricted the fructose-induced
      alterations remarkably.

PMID- 17173887
TI  - It's the way that you, er, say it: hesitations in speech affect language
      comprehension.
AB  - Everyday speech is littered with disfluency, often correlated with the production
      of less predictable words (e.g., Beattie & Butterworth [Beattie, G., &
      Butterworth, B. (1979). Contextual probability and word frequency as determinants
      of pauses in spontaneous speech. Language and Speech, 22, 201-211.]). But what
      are the effects of disfluency on listeners? In an ERP experiment which compared
      fluent to disfluent utterances, we established an N400 effect for unpredictable
      compared to predictable words. This effect, reflecting the difference in ease of
      integrating words into their contexts, was reduced in cases where the target
      words were preceded by a hesitation marked by the word er. Moreover, a subsequent
      recognition memory test showed that words preceded by disfluency were more likely
      to be remembered. The study demonstrates that hesitation affects the way in which
      listeners process spoken language, and that these changes are associated with
      longer-term consequences for the representation of the message.

PMID- 17173888
TI  - Fast simulation of solid tumors thermal ablation treatments with a 3D reaction
      diffusion model.
AB  - An efficient computational method for near real-time simulation of thermal
      ablation of tumors via radio frequencies is proposed. Model simulations of the
      temperature field in a 3D portion of tissue containing the tumoral mass for
      different patterns of source heating can be used to design the ablation
      procedure. The availability of a very efficient computational scheme makes it
      possible to update the predicted outcome of the procedure in real time. In the
      algorithms proposed here a discretization in space of the governing equations is
      followed by an adaptive time integration based on implicit multistep formulas. A
      modification of the ode15s MATLAB function which uses Krylov space iterative
      methods for the solution of the linear systems arising at each integration step
      makes it possible to perform the simulations on standard desktop for much finer
      grids than using the built-in ode15s. The proposed algorithm can be applied to a
      wide class of nonlinear parabolic differential equations.

PMID- 17173889
TI  - Pax2 regulates neuronal-glial cell fate choice in the embryonic optic nerve.
AB  - During development, neural cell fate in the vertebrate optic nerve is restricted
      to the astroglial lineage. However, when isolated from the embryo and explanted
      in vitro, optic nerve progenitors generate neurons instead of astrocytes,
      suggesting that neuronal potentialities exist and are repressed in progenitors in
      vivo. Here we have investigated the mechanisms controlling cell fate in the optic
      nerve. The optic nerve is characterized by expression of the homeodomain
      transcription factor Pax2 which is maintained in differentiated astrocytes. We
      have observed that Pax2 is rapidly down-regulated in explanted optic nerves that
      generate neurons, and that its overexpression by electroporation in the optic
      nerve, or ectopically in the neural tube, is sufficient to block neuronal
      differentiation and allow glial development, showing that Pax2 plays a major role
      in controlling cell fate in the optic nerve. In vitro and ex vivo experiments
      further show that a signaling cascade that involves successively Sonic hedgehog
      and FGF is required to maintain Pax2 expression in optic nerve precursors whereby
      inhibiting the neuronal fate and promoting astroglial differentiation.

PMID- 17173890
TI  - Polycyclic aromatic hydrocarbon (PAH) contamination in San Francisco Bay: a 10
      year retrospective of monitoring in an urbanized estuary.
AB  - Polycyclic aromatic hydrocarbons (PAH) are widespread contaminants in the San
      Francisco Bay. Several exceedances of water quality criteria raise the
      possibility that PAH may be impacting aquatic biota. The Regional Monitoring
      Program for Water Quality in the San Francisco Estuary (RMP) has collected annual
      monitoring data on PAH in the Bay since 1993. Analysis of Bay water, sediment,
      and mussel SigmaPAH concentration data showed that there were very few
      significant (P < 0.05) increasing or decreasing temporal trends in SigmaPAH
      concentrations in the Bay during the period of 1993-2001. Wet and dry season
      input of PAH did not show any major influence on water SigmaPAH concentrations
      over the same period. Based on their relative contribution to the estimated total
      maximum PAH loading (10,700 kg/yr) into the Bay, the PAH loading pathways are
      ranked as storm water runoff ( approximately 51%) >tributary inflow (
      approximately 28%) >wastewater treatment plant effluent ( approximately 10%)
      >atmospheric deposition ( approximately 8%) >dredged material disposal (
      approximately 2%). The PAH sediment quality threshold of 1000 ng/g, which has
      been previously suggested by NOAA to protect estuarine fish such as English sole
      against adverse health effects, was frequently exceeded at individual monitoring
      stations (11 of the 26 stations exceeded the threshold over 50% of the time).
      Modeling results have shown that the predominant loss pathway for PAH is
      degradation in sediments, and unless external loading levels of PAH are
      controlled, the Bay is not expected to recover rapidly.

PMID- 17173892
TI  - Oxidative renal damage in pyelonephritic rats is ameliorated by montelukast, a
      selective leukotriene CysLT1 receptor antagonist.
AB  - Urinary tract infections may induce severe inflammation, transient impairment in
      renal function and scar formation, ranging in severity from acute symptomatic
      pyelonephritis to chronic pyelonephritis, which have a potential to lead to renal
      failure and death. The present study aimed to investigate the possible protective
      effect of montelukast, a selective antagonist of cysteinyl leukotriene receptor 1
      (leukotriene CysLT1), against Escherichia coli-induced oxidative injury and
      scarring in renal tissue. Wistar rats were injected 0.1 ml of E. coli (ATCC 25922
      10(10) cfu/ml) or saline into left renal medullae. Six rats were assigned as the
      sham group and were given 0.1 ml 0.9% NaCl. Pyelonephritic rats were treated with
      either saline or montelukast immediately after surgery and at daily intervals.
      Twenty-four hours or one week after E. coli injection, rats were decapitated and
      the kidney samples were taken for histological examination or determination of
      renal malondialdehyde, glutathione (GSH) levels, myeloperoxidase (MPO) activity,
      and collagen contents. Formation of reactive oxygen species in renal tissue
      samples was monitored by using chemiluminescence technique with luminol and
      lucigenin probes. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH)
      activity were measured in the serum samples. E. coli inoculation caused
      significant increases in malondialdehyde level, MPO activity, chemiluminescence
      levels and collagen content, while GSH level was decreased in the renal tissues
      (p<0.05-0.001). On the other hand, serum TNF-alpha, LDH, blood urea nitrogen and
      serum creatinine levels were elevated in the pyelonephritic rats as compared to
      control group. Leukotriene CysLT1 receptor antagonist montelukast reversed all
      these biochemical indices, as well as histopathological alterations, that were
      induced by acute pyelonephritis. It seems likely that montelukast protects kidney
      tissue by inhibiting neutrophil infiltration, balancing oxidant-antioxidant
      status, and regulating the generation of inflammatory mediators suggesting a
      future role for leukotriene CysLT1 receptor antagonists in the treatment of
      pyelonephritis.

PMID- 17173891
TI  - Nociceptin/orphanin FQ blocks the antinociception induced by mu, kappa and delta
      opioid agonists on the cold water tail-flick test.
AB  - Nociceptin/orphanin FQ (N/OFQ), a 17-amino-acid peptide, is an endogenous agonist
      whose receptor is similar in sequence to mu, delta and kappa opioid receptors. It
      has been reported that N/OFQ can block antinociceptive effects induced by opioid
      receptor agonists in the radiant heat tail-flick test and warm water tail
      withdrawal test. The present study was designed to see the effect of N/OFQ on
      antinociception induced by opioid receptor agonists in the cold water tail-flick
      (CWT) test, which measures a different type of pain. In adult male Sprague-Dawley
      (S-D) rats given subcutaneous (s.c.) injections of saline or morphine (8 mg/kg),
      intracerebroventricular (i.c.v.) injection of N/OFQ (18 microg) 15 min later
      produced a significant reversal of morphine antinociception (P<0.01, ANOVA
      followed by Duncan's test), compared to the corresponding saline control group.
      Saline (t=+15 min, i.c.v.) had no effect on s.c. morphine antinociception
      (P>0.01), compared to the corresponding saline control group. When the kappa
      opioid receptor agonist spiradoline (80 mg/kg, s.c.) was used instead of
      morphine, similar results were observed. In another series of experiments, it was
      found that i.c.v. injection of N/OFQ (18 microg) reversed the antinociception
      induced by i.c.v. injection of the selective mu opioid agonist PL017 (2 microg),
      delta opioid agonist DPDPE (50 ng) and kappa opioid agonist dynorphin (21.5
      microg), respectively. These results indicate that N/OFQ may be an endogenous
      anti-opioid peptide in the brain of rats in the CWT test.

PMID- 17173893
TI  - Ischemic preconditioning modulates ischemia-reperfusion injury in the rat lung:
      role of adenosine receptors.
AB  - Recent studies have been focused on the protective role of ischemic
      preconditioning against ischemia-reperfusion injury of the lung occurring
      following cardiopulmonary by-pass surgery and lung or heart transplantation. The
      present study was undertaken to investigate the role of adenosine in ischemic
      preconditioning in the isolated buffer-perfused rat lung. Since the pulmonary
      perfusion flow rate and left atrial pressure were constant, changes in pulmonary
      arterial pressure directly reflect changes in pulmonary vascular resistance. When
      compared to control values, ischemia-reperfusion injury in the form of 2 h of
      normothermic ischemia significantly reduced the pulmonary vasoconstrictor
      response to phenylephrine and KCl, increased wet-to-dry lung weight ratios and
      increased malondialdehyde content of rat lungs. Ischemic preconditioning in the
      form of one cycle of 5 min of ischemia and reperfusion applied prior to ischemia
      reperfusion, as well as, adenosine preconditioning in the form of adenosine
      infusion prior to ischemia-reperfusion independently prevented the reduction in
      pulmonary vasoconstrictor responses and the increases in pulmonary edema and
      malondialdehyde formation in response to ischemia-reperfusion injury.
      Pretreatment with adenosine receptor antagonists, theophylline or 8-cyclopentyl
      1,3-dipropyl xanthine (DPCPX) prior to ischemic preconditioning or adenosine
      preconditioning abolished the protective effects of preconditioning by ischemic
      preconditioning and adenosine preconditioning. The present data demonstrate that
      ischemic preconditioning and adenosine preconditioning prevent the vascular and
      biochemical alterations studied in response to ischemia-reperfusion injury in the
      pulmonary vascular bed of the rat. Results of the present study suggest
      activation of adenosine A(1) receptors mediates the protective properties of
      ischemic preconditioning and adenosine preconditioning on ischemia-reperfusion
      injury in the lung. Moreover, the present data further suggest selective
      adenosine receptor agonists may be useful as pharmacologic preconditioning agents
      in preventing ischemia-reperfusion injury in lung transplantation and other forms
      of pulmonary vascular ischemia.

PMID- 17173896
TI  - AnCrpA, a cAMP receptor protein, regulates nif-related gene expression in the
      cyanobacterium Anabaena sp. strain PCC 7120 grown with nitrate.
AB  - Target genes for a cAMP receptor protein, AnCrpA, were screened using an Anabaena
      oligonucleotide microarray and real-time quantitative reverse transcription
      polymerase chain reaction (RT-PCR) analysis. Several gene expressions, including
      some involved in nitrogen fixation, were downregulated in the ancrpA disruptant
      when cells were grown with nitrate. Electrophoretic mobility shift assays (EMSAs)
      revealed that AnCrpA bound to the 5' upstream region of nifB, all1439, hesA,
      all5347, hglE and coxBII in the presence of cAMP, and all of them are related
      with nitrogen fixation. A possible AnCrpA-binding site in the 5' upstream region
      of nifB was predicted using hidden Markov model (HMM) software based on the
      result of in vitro selection of AnCrpA-binding sequences, and the binding was
      confirmed by EMSA. Thus, AnCrpA regulates the expressions of gene clusters
      related to nitrogen fixation in the presence of nitrate.

PMID- 17173895
TI  - 4-Hydroxynonenal, a product of oxidative stress, leads to an antioxidant response
      in optic nerve head astrocytes.
AB  - Oxidative stress has been implicated in the pathogenesis of several
      neurodegenerative disorders including primary open-angle glaucoma (POAG) an optic
      neuropathy characterized by loss of retinal ganglion cell (RGC) axons and
      remodeling of the optic nerve head (ONH). Previous findings in glaucomatous
      astrocytes suggested increased oxidative stress and lipid peroxidation in human
      optic nerves. We studied the dose and time dependent effects of 4-hydroxynonenal
      (HNE), a by-product of lipid peroxidation, on the viability of primary cultures
      of human ONH astrocyte. A significant depletion of glutathione (GSH) level was
      observed in normal astrocytes after exposure to HNE for 1 h and 3 h. Untreated
      glaucomatous astrocytes exhibited depleted levels of GSH which increased slightly
      after exposure to HNE. Both normal and glaucomatous astrocytes recovered GSH
      levels after 24 h of removal of HNE. HNE caused significant increases in
      expression of antioxidant enzymes, glutamate cysteine ligase catalytic subunit
      (GCLC), aldo-keto reductase 1C family member 1 (AKR1C1) and glutathione S
      transferase-alpha4 (GSTA4). HNE induced expression of the transcription factor
      Nrf2, which coordinates the upregulation of detoxification enzymes. In addition,
      ONH astrocytes responded to HNE by activation and transcription of cFOS and NFkB,
      which regulate physiological protective responses against oxidative stress. Our
      results indicate that ONH astrocytes exhibit a strong antioxidant response to HNE
      treatment by inducing the transcription factors cFOS, NFkB, and Nrf2, which
      upregulate the expression of GCLC, to produce more GSH in the cell. AKR1C1 was
      also upregulated after HNE treatment to inactivate HNE, independent of GSH
      availability in the cells. Collectively these data indicate that ONH astrocytes
      can efficiently counteract the neurotoxic effects of HNE offering protection in
      the optic nerve by releasing GSH and antioxidant enzymes to eliminate the
      products of chronic oxidative stress.

PMID- 17173894
TI  - Comparative studies between species that do and do not exhibit the washout
      effect.
AB  - Ocular perfusion studies from all non-human species performed to date
      consistently demonstrate a perfusion-volume-dependent increase in aqueous outflow
      facility known as the "washout" effect. However, this "washout" effect does not
      occur in human eyes. We have recently documented that, in bovine eyes, the
      washout associated increase in facility correlates with the extent of physical
      separation between the juxtacanalicular connective tissue (JCT) and the inner
      wall endothelium lining the aqueous plexus (the bovine equivalent of Schlemm's
      canal). We hypothesize that if washout truly correlates with inner wall/JCT
      separation then this separation should not occur in human eyes that do not
      exhibit the washout effect, even after prolonged perfusion. Eight enucleated
      human and eight bovine eyes were used in this study. Aqueous humor outflow
      facility was measured at 15 mmHg for long-duration (3 h) or short-duration (30
      min to 1 h) perfusion (n=4 for each group). All eyes were perfusion-fixed at 15
      mmHg, and examined morphologically with both light and electron microscopy. In
      bovine eyes, outflow facility increased 81% (p=0.049) from 1.06 +/- 0.06
      microl/min per mmHg (mean+/-SEM) at baseline to 1.92 +/- 0.30 microl/min per mmHg
      after 3 h due to washout. The pre-fixation outflow facility in long-duration eyes
      (1.92 +/- 0.30 microl/min per mmHg) was 2-fold greater than pre-fixation facility
      in short-duration eyes (0.92 +/- 0.11 microl/min per mmHg; p=0.0387). In human
      eyes, washout was not observed; baseline outflow facility was similar between
      both groups (0.18 +/- 0.02 vs. 0.25 +/- 0.08 microl/min per mmHg; p=0.518);
      however, pre-fixation outflow facility in long-duration eyes showed a 40%
      decrease compared to baseline outflow facility in those same eyes (p=0.017,
      paired Student's t-test). In bovine eyes, significant expansion and rarefaction
      of the JCT and inner wall/JCT separation was much more prevalent in long-duration
      eyes, and data from all bovine eyes revealed a correlation between the extent of
      inner wall/JCT separation and the absolute value of outflow facility measured
      immediately prior to fixation (p=0.0024) as well as the washout-induced increase
      in outflow facility (p=0.0006). In human eyes, no significant morphologic
      differences were observed between long- and short-duration perfusion, with no
      observed change in inner wall/JCT separation or expansion between the two groups.
      Morphologic analysis revealed that the previously described "cribriform plexus"
      of elastic-like fibers was far more extensive in the JCT of human eyes, appearing
      to form numerous connections to the inner wall endothelium. The cribriform plexus
      appears to function as a mechanical tether that maintains inner wall/JCT
      connectivity in human eyes by opposing hydrodynamic forces generated during
      perfusion, potentially explaining the lack of washout in humans.

PMID- 17173897
TI  - Proliferation and apoptosis in PhIP-induced rat mammary gland carcinomas with
      elevated phosphotyrosine-STAT5a.
AB  - In the present study we addressed whether proliferation and apoptosis in 2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary gland carcinomas were
      different between carcinomas with high and low expression of phosphotyrosine (pY)
      STAT5a. We determined that carcinomas with high pY-STAT5a were more proliferative
      (MIB5 immunostaining) and had a higher expression of cyclin D1 and estrogen
      receptor alpha. Furthermore, carcinomas with elevated pY-STAT5a demonstrated
      lower apoptosis as measured by the TUNEL assay and the Bcl-2 to Bax ratio, and
      showed increased expression of the long and short isoforms of the prolactin
      receptor. The results of this study are consistent with the notion that activated
      STAT5a may provide a growth advantage in some types of mammary gland cancers.

PMID- 17173898
TI  - Tissue perfusion-controlled guided biopsies are essential for the outcome of
      testicular sperm extraction.
AB  - OBJECTIVE: To determine if there are areas of major and minor perfusion in a
      single testicle, and if the quality and quantity of sperm are correlated with the
      level of perfusion, we collected testicular tissue from areas with different
      levels of perfusion. DESIGN: Controlled clinical study. SETTING: Consecutive
      patients with azoospermia. PATIENT(S): Patients with azoospermia undergoing
      testicular sperm extraction (TESE) biopsy for the retrieval of sperm to be used
      in an assisted reproduction program. INTERVENTION(S): Perfusion mapping was
      performed with the use of color Doppler ultrasound. Areas with different levels
      of perfusion were marked with needles. After incision with radiofrequency
      cutting, the exposed tissue was examined with a laser Doppler flowmeter, and
      biopsies were taken for TESE and histology. Sperm were analyzed using World
      Health Organization criteria, and prepared for intracytoplasmic sperm injection
      (ICSI). MAIN OUTCOME MEASURE(S): Correlation of sperm quality and quantity in
      testicular-tissue biopsies, with tissue-perfusion units (TPU) measured by laser
      Doppler flowmeter. RESULT(S): From 40 biopsies taken from 20 testicles of 12
      patients, tissue was analyzed for sperm quality and quantity. Sperm quality was
      highest in areas of high tissue perfusion. In areas of 70 TPU, 72.3% progressive
      sperm were detected, whereas in areas of 10 TPU, only 13.3% progressive sperm and
      elevated numbers of precursor cells could be observed. The number of motile sperm
      isolated from tissue samples correlated well with the intensity of tissue
      perfusion. CONCLUSION(S): We have shown for the first time that in patients
      suffering from azoospermia, sperm quality and quantity depend on tissue perfusion
      within the testicle.

PMID- 17173899
TI  - Salpingectomy increases peri-implantation endometrial HOXA10 expression in women
      with hydrosalpinx.
AB  - OBJECTIVE: To determine whether women with hydrosalpinx would have diminished
      endometrial HOXA10 expression and whether salpingectomy would reverse HOXA10
      suppression. The homeobox gene HOXA10 is a transcription factor that is necessary
      for embryo implantation; its expression in human endometrium correlates with
      receptivity and implantation. Increased endometrial HOXA10 expression may be one
      mechanism by which salpingectomy results in increased implantation rates in IVF.
      DESIGN: Prospective clinical trial. SETTING: Academic medical center. PATIENT(S):
      Women with unilateral or bilateral hydrosalpinx. INTERVENTION(S): Expression of
      HOXA10 was examined prospectively during the midluteal phase in endometrium
      obtained from infertile women (n = 9) with hydrosalpinges before and after
      salpingectomy, as well as from fertile controls (n = 6). Quantitative HOXA10 mRNA
      expression was determined by real-time reverse-transcription polymerase chain
      reaction, and HOXA10 protein expression was determined by immunohistochemistry.
      MAIN OUTCOME MEASURE(S): Expression of HOXA10 mRNA and protein. RESULT(S):
      Expression of HOXA10 mRNA was significantly lower in infertile women with
      hydrosalpinges, compared with the case of fertile controls. Salpingectomy
      resulted in a statistically significant, 15-fold increase in endometrial HOXA10
      expression. Immunohistochemical analysis confirmed the quantitative real-time
      reverse-transcription polymerase chain reaction findings. Increased HOXA10
      expression was evident in both glandular epithelial cells and endometrial stroma.
      CONCLUSION(S): HOXA10 is necessary for implantation. Here, we demonstrate
      decreased HOXA10 expression in response to hydrosalpinx fluid as a potential
      molecular mechanism for diminished implantation rates. Salpingectomy restores
      endometrial HOXA10 expression. This may be one mechanism by which salpingectomy
      results in augmented implantation rates in IVF.

PMID- 17173900
TI  - Use of gonadotropin-releasing hormone agonists in patients with Hodgkin's disease
      for preservation of ovarian function and reduction of gonadotoxicity related to
      chemotherapy.
AB  - In young women receiving chemotherapy for Hodgkin's disease, the combined use of
      triptorelin and tibolone cotreatment may be a useful tool for preserving ovarian
      function because all but three (10%) of the women in this treatment group
      returned to spontaneous ovulation and menses, in contrast to 23% of subjects in
      the control group (P<.05). No significant differences were observed in bone
      mineral density between groups.

PMID- 17173901
TI  - Spontaneous viable pregnancies in cervical and rectal endometriosis: a report of
      two cases.
AB  - OBJECTIVE: To report two cases of advanced pelvic endometriosis, both with deep
      rectal involvement and one with extensive cervical involvement appearing like a
      carcinoma, where both patients achieved spontaneous pregnancy and delivered
      viable babies. DESIGN: Case report. SETTING: Institute of Reproductive Medicine.
      PATIENT(S): Two nulliparous patients, one with extensive cervical and rectal and
      other with deep rectal endometriosis and primary infertility. INTERVENTION(S):
      Medical management. MAIN OUTCOME MEASURE(S): Description and treatment of two
      patients with advanced pelvic endometriosis and pregnancy. RESULT(S): Delivery of
      viable babies in both cases. CONCLUSION: Prolonged medical treatment may have
      helped to arrest the progression of the disease by restoring anatomic proximity
      leading to spontaneous pregnancy in both cases.

PMID- 17173902
TI  - Impact of aromatase inhibitors on adhesion formation in a rat model.
AB  - OBJECTIVE: To investigate the antiadhesion potential of tamoxifen and anastrozole
      in a rat uterine horn model. DESIGN: Experimental animal study. SETTING:
      University animal laboratory. ANIMAL(S): Forty-five female Wistar albino rats.
      INTERVENTION(S): We examined the effects of tamoxifen and anastrozole to reduce
      the extent and severity of postoperative adhesions in a rat uterine horn model:
      the control group received no therapy while the second and third groups received
      500 mug/day tamoxifen and 0.2 mg/kg/day anastrazole, respectively, through an
      enteric tube, starting 5 days before surgery. These protocols were continued for
      14 days after the surgery until the rats were killed. MAIN OUTCOME MEASURE(S):
      Adhesions were scored according to their extent and severity, and specimens were
      also evaluated and scored histologically according to the following features:
      inflammation, fibroblastic activities, foreign body reaction, collagen formation,
      and vascular proliferation. RESULT(S): Anastrozole had the lowest mean adhesion
      scores, and these scores were significantly different from those of the controls.
      However, there were no statistically significant differences between control and
      tamoxifen groups and between tamoxifen and anastrozole groups. Histologic scores
      were lowest in the anastrozole group, which were statistically different from
      those of the tamoxifen and anastrozole groups, whereas scores of the control
      group were not statistically different from those of the tamoxifen group.
      CONCLUSION(S): Anastrazole decreased postsurgical adhesion scores by both visual
      scores and histologic analyses in a rat model. Further experimental and clinical
      trials are required to confirm these results.

PMID- 17173903
TI  - Expression profile of several genes in human myometrium and uterine leiomyoma.
AB  - OBJECTIVE: To screen several genes that are differentially expressed in uterine
      leiomyoma and matched unaffected myometrium by using microarray-based
      hybridization and real-time polymerase chain reaction analyses. DESIGN: Screen by
      arrays for < or =2,400 known genes in leiomyoma and control myometrium. SETTING:
      University clinical research laboratory. PATIENT(S): Four patients with leiomyoma
      scheduled for surgery during the proliferative phase. INTERVENTION(S): Four
      paired samples of leiomyoma and adjacent myometrium were obtained from patients
      undergoing hysterectomy. MAIN OUTCOME MEASURE(S): Fold-changes in expression of
      leiomyoma and matched myometrium (L/M). RESULT(S): A comparison of expression
      patterns revealed 73 genes significantly up- or down-regulated in each paired
      tissue sample, of which 30 genes showed increased expression (mean L/M of >2) and
      43 showed decreased expression (mean L/M of <0.5) in leiomyoma compared with
      normal myometrium. When considering only growth factors, pleiotropin (PTN) was
      expressed 3.5-fold more in leiomyomas compared with in myometrium. No other
      growth factors were similarly affected. In addition, real-time polymerase chain
      reaction analysis correlated well with microarray data. CONCLUSION(S): Data
      obtained from the present study suggest that several genes are selectively
      overexpressed in leiomyomas compared with in myometrium. Increased expression of
      growth factor PTN may represent a promising target for therapy.

PMID- 17173904
TI  - Laparoscopic ovariectomy for whole human ovary cryopreservation: technical
      aspects.
AB  - OBJECTIVE: To describe the technique of laparoscopic ovariectomy with a view to
      cryopreservation of a whole ovary with its vascular pedicle. DESIGN: Descriptive
      study. SETTING: Gynecology research unit in a department of gynecology in a
      university hospital. PATIENT(S): Women with indications for chemotherapy or
      radiotherapy who are at high risk of premature ovarian failure. INTERVENTION(S):
      Laparoscopic ovariectomy for whole ovary cryopreservation in nine patients. MAIN
      OUTCOME MEASURE(S): Feasibility of laparoscopic ovariectomy for whole ovary
      cryopreservation and later autotransplantation without delaying chemotherapy.
      RESULT(S): The whole ovary was successfully removed by laparoscopy and
      cryopreserved by arterial catheterization in all nine patients. CONCLUSION(S):
      Ovariectomy with a view to whole ovary cryopreservation for future
      transplantation may be performed by laparoscopy. Great care must be taken to
      remove the ovary, together with a large part (> or =5 cm) of the
      infundibulopelvic ligament, allowing dissection of the ovarian vessels, perfusion
      with a cryoprotective medium, and cryopreservation for subsequent autografting of
      the whole ovary. The period of ischemia between ligation of the ovarian pedicle
      and ovarian cryopreservation must be as short as possible.

PMID- 17173905
TI  - Establishing a human chorionic gonadotropin cutoff to guide methotrexate
      treatment of ectopic pregnancy: a systematic review.
AB  - OBJECTIVE: Successful medical management of an ectopic pregnancy is inversely
      associated with initial hCG level. The purpose of this publication is to assess
      whether there is a level of hCG above which failure rate substantially increases.
      DESIGN: A systematic review and summary analysis was performed, including studies
      reporting methotrexate treatment outcomes as stratified by various hCG ranges.
      SETTING: Academic medical center. PATIENT(S): Review of published information
      regarding patients treated with methotrexate. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Success and failure rate of medical management. RESULT(S): Five
      observational studies, including 503 women, were found that reported successes in
      using single-dose methotrexate stratified by initial hCG concentration. Failure
      rates increase with increasing hCG levels. A substantial and statistically
      significant increase in failure rates is seen when comparing patients who have
      initial hCG levels of >5,000 mIU/mL with those who have initial levels of <5,000
      mIU/mL (odds ratio: 5.45; 95% confidence interval: 3.04, 9.78). The failure rate
      for women who had an initial concentration between 5,000 and 9,999 mIU/mL was
      significantly higher than that for those who had initial levels between 2,000 and
      4,999 mIU/mL (odds ratio: 3.76; 95% confidence interval: 1.16, 12.33).
      CONCLUSION(S): Results support a substantial increase in failure of medical
      management with single-dose methotrexate when the initial hCG is above 5,000
      mIU/mL. Methotrexate should be used with caution in patients with ectopic
      pregnancy who present with hCG levels above this level.

PMID- 17173906
TI  - Utilization of high-security straws for embryo freezing in an in vitro
      fertilization program: a prospective, randomized study.
AB  - OBJECTIVE: To compare the outcome of frozen-thawed ET cycles where embryos had
      been stored in conventional versus ionomeric resin-based, high-security straws
      (HSSs). DESIGN: Prospective, randomized study. SETTING: Private assisted
      reproduction unit. PATIENT(S): Three hundred and six freeze cycles, and 197 thaw
      cycles. INTERVENTION(S): Day 3 embryos (n = 1,268) were frozen, and 517 were
      thawed using HSSs. Alternately, day 3 embryos (n = 1,228) were frozen, and 505
      were thawed using conventional straws. MAIN OUTCOME MEASURE(S): Cryosurvival,
      cleavage and morulae formation rates, and clinical pregnancy, implantation, and
      multiple pregnancy rates. RESULT(S): Although cycle characteristics did not show
      any differences, the cryosurvival rate was higher in the HSS group (94.7%) than
      in the conventional straw group (86%), as was the morulae formation rate (58.7%
      versus 42.7%). Despite a similar number of embryos being transferred, the
      clinical pregnancy rate (PR) was higher in the HSS group, but the difference
      lacked statistical significance (42.5% versus 31.2). Implantation rates (19.4%
      versus 11.4%) and multiple PRs (41.8% versus 16.6%) were significantly higher in
      the HSS group than in the conventional straw group. CONCLUSION(S): High-security
      straws are high effective in human embryo cryopreservation, because they provide
      higher cryosurvival and implantation rates, as well as a lower risk of cross
      contamination compared to conventional straws.

PMID- 17173907
TI  - Human chorionic gonadotropin administration vs. luteinizing monitoring for
      intrauterine insemination timing, after administration of clomiphene citrate: a
      meta-analysis.
AB  - OBJECTIVE: To systematically compare hCG administration as a method for
      intrauterine insemination (IUI) timing with conservative urinary LH surge
      detection in infertility treatment. DESIGN: Meta-analysis of prospective and
      retrospective trials. SETTING: Tertiary fertility and IVF center. PATIENT(S): One
      thousand four hundred sixty-one patients who received hCG after a clomiphene
      citrate regimen, compared with 1,162 patients who had an LH surge detection for
      IUI timing. INTERVENTION(S): Both MEDLINE and Cochrane Collaboration were
      searched. References of retrieved articles were included in the search. The meta
      analysis included all controlled trials examining the effectiveness of hCG
      administration before IUI on clinical-pregnancy rates in comparison with LH
      detection. Two independent reviewers performed data extraction. MAIN OUTCOME
      MEASURE(S): Pregnancy rates. RESULT(S): Seven studies with 2,623 patients were
      included in the meta-analysis (1,461 patients received hCG, and 1,162 had LH
      surge detection). When all studies were combined, patients who received hCG
      before IUI demonstrated lower clinical-pregnancy rates than did women who had IUI
      after spontaneous ovulation (odds ratio, 0.74; 95% confidence interval, 0.57
      0.961). In subgroup analysis of studies that considered ovulatory dysfunction to
      be the infertility reason, the results favored women who received hCG. In
      contrast, across studies that reported male factor as the infertility reason, as
      well as across studies including women with unexplained infertility, results
      appeared to favor the LH surge detection approach. However, none of those
      subgroup analyses reached statistical significance. CONCLUSION(S): Available data
      do not demonstrate a consistent, clinically important benefit of hCG-induced
      ovulation compared with spontaneous ovulation for IUI timing.

PMID- 17173908
TI  - Papillary type of early common bile duct cancer.

PMID- 17173909
TI  - EUS-guided injection of paclitaxel (OncoGel) provides therapeutic drug
      concentrations in the porcine pancreas (with video).
AB  - BACKGROUND: OncoGel (ReGel/paclitaxel) is an intralesional injectable formulation
      of the chemotherapeutic drug, paclitaxel, for local tumor management. OBJECTIVE:
      The aim of this study was to determine if a minimally invasive EUS-guided
      injection of paclitaxel, bound to a thermosensitive gel carrier, would lead to
      therapeutic tissue concentrations of the chemotherapeutic agent in the porcine
      pancreas. DESIGN: Eight Yorkshire breed pigs were sedated by general anesthesia
      and OncoGel was injected, under EUS-guidance, with a 22-gauge needle into the
      tail of the pancreas. MAIN OUTCOME MEASUREMENTS: During the 7-day (n = 4) or 14
      day (n = 4) observational period, the animals were monitored by serum levels of
      amylase and lipase, and by a CT on day 4. The outcome was determined by gross and
      microscopic evidence of inflammation of the pancreas, clinical tolerance, and
      quantitation of tissue paclitaxel concentrations. RESULTS: Eight pigs underwent
      injection of 1, 2, 3, or 4 mL OncoGel (6 mg paclitaxel per 1 mL OncoGel) (n = 2
      per group). An intrapancreatic hyperechoic focus, with an average diameter of 2.1
      +/- 0.8 cm, was visible by EUS, and a hypodense area in the tail of the pancreas
      was visible by contrast CT. Clinically, the animals appeared to tolerate the
      procedure without sequelae. Blood levels of amylase and lipase were normal. At
      euthanasia, a depot of OncoGel, with an average diameter of 14.7 +/- 5.0 mm), was
      located both grossly and histologically in the pancreatic tail. After 14 days,
      clinically significant tissue concentrations of paclitaxel were detected at a
      distance of 30 to 50 mm from the depot in the animals that underwent an injection
      of 3 and 4 mL of the agent (n = 2). CONCLUSIONS: The EUS-guided injection of
      OncoGel into the pancreas of the pig provided high and sustained localized
      concentrations of paclitaxel. This technique is a potential minimally invasive
      local treatment option for unresectable pancreatic tumors.

PMID- 17173910
TI  - Diffuse luminal ulceration resulting from duodenal plasmacytoma.

PMID- 17173911
TI  - Minor complications in colonoscopy: Mars versus Venus, and preps matter too.

PMID- 17173912
TI  - Residue-free sodium phosphate tablets (OsmoPrep) versus Visicol for colon
      cleansing: a randomized, investigator-blinded trial.
AB  - BACKGROUND: The bowel purgative Visicol contains microcrystalline cellulose (MCC)
      residue, which may impair full visibility during a colonoscopy. An MCC residue
      free sodium phosphate (RF-NaP; OsmoPrep) tablet was developed. OBJECTIVE: To
      investigate appropriate RF-NaP dosing. DESIGN: Phase 2, randomized, investigator
      blinded study. SETTING: Six research centers in the United States. PATIENTS AND
      INTERVENTIONS: Patients undergoing a colonoscopy received Visicol (n = 34) or 1
      of 6 RF-NaP regimens administered as either split (S) dosing (the evening before
      and the day of colonoscopy) or evening-only (E) dosing. Dosing regimens for RF
      NaP were 40 tablets S, 3 every 15 minutes (n = 33); 40 tablets S, 4 every 15
      minutes (n = 34); 32 tablets E, 4 every 15 minutes (n = 34); 32 tablets S, 4
      every 15 minutes (n = 36); 28 tablets E, 4 every 15 minutes (n = 34); 28 tablets
      S, 4 every 15 minutes (n = 34). Visicol was administered as 40 tablets S, 3 every
      15 minutes. MAIN OUTCOME MEASURE: Overall colon cleansing (OCC) was assessed by a
      physician questionnaire (4-point scale, based on colonic contents). An OCC rating
      of "excellent" or "good" was considered a response. Safety measures were also
      monitored. RESULTS: Split dosing with RF-NaP was associated with high OCC and
      achieved response rates of 90%, 97%, and 100% for 28, 32, and 40 tablets,
      respectively, compared with 86% for Visicol. In addition, RF-NaP evening-only
      regimen response rates were 90% (32 tablets) and 72% (28 tablets). Transient
      shifts in electrolyte levels were reduced, and GI adverse events were less common
      with lower RF-NaP dose regimens. CONCLUSIONS: Administration of RF-NaP retains
      the benefits of a tablet purgative but eliminates MCC issues. Split dosing and 32
      tablet evening-only dosing of RF-NaP tablets were efficacious and well tolerated,
      and split dosing of RF-NaP tablets is recommended.

PMID- 17173913
TI  - Colorectal cancer screening with nurse-performed flexible sigmoidoscopy: results
      from a Canadian community-based program.
AB  - BACKGROUND: Despite highest-quality evidence that early detection of colorectal
      cancer (CRC) can lead to reduced mortality, no organized CRC screening programs
      exist in Canada. OBJECTIVE: To report the safety, the feasibility, and the
      detection rate for the first Canadian community-based nurse-performed flexible
      sigmoidoscopy (FS) screening program for CRC, established in 1999. DESIGN: Cross
      sectional analysis of data collected from a prospective study of FS done by
      nurses from March 1999 to November 2002. Estimate of differences between men and
      women in FS findings, with relative risks. Logistic regression used to calculate
      odds ratios for advanced neoplasia. SETTING: Endoscopy suite of a community
      hospital. PATIENTS: Asymptomatic men and women > or =50 years, with no previous
      history of CRC. INTERVENTION: FS done by a nurses, and colonoscopy for persons
      with abnormalities done by an experienced gastroenterologist. MAIN OUTCOME
      MEASUREMENTS: Mean depth of insertion of endoscope; duration of FS procedure;
      number and location of polyps found during FS; number, location, and type of
      polyps found during colonoscopy. RESULTS: A total of 1818 individuals (mean age,
      62 years) underwent nurse-performed FS (mean duration, 7.3 minutes; mean depth of
      insertion of the endoscope, 53.5 cm), without complications. Results of the FS
      were abnormal for 240 (13.2%) of the 1818 participants; 231 (12.7%) underwent
      colonoscopy. Distal neoplasms (adenomas or cancer) were detected in 8.7%
      (158/1818). After adjustment for age and family history of CRC, the risk of
      advanced neoplasm in the distal colon for men was about twice that for women
      (odds ratio 1.95, 95% confidence interval 1.21-3.14). Cancer was detected in 5 of
      the 1818 participants screened (0.28%), and high-grade dysplasia was detected in
      an additional 5 (0.28%). One of the cancers and all the lesions with high-grade
      dysplasia were treated endoscopically. CONCLUSIONS: Our community-based nurse
      performed FS screening program was feasible and safe. The referral rate for
      colonoscopy was 13%, and the cancer detection rate was 2.8 per 1000 persons
      screened.

PMID- 17173915
TI  - Intussusception and bleeding of a Meckel's diverticulum diagnosed by colonoscopy.

PMID- 17173914
TI  - Incidence of minor complications and time lost from normal activities after
      screening or surveillance colonoscopy.
AB  - BACKGROUND: Few studies address the development of minor complications after
      screening or surveillance colonoscopy. OBJECTIVES: Our purpose was to examine in
      previously asymptomatic people the incidence of new symptoms after colonoscopy,
      risk factors for symptoms, and patients' perceptions of this examination. DESIGN:
      Prospective cohort study. Patients completed a standardized interview at 7 and 30
      days after colonoscopy. PATIENTS: A total of 502 patients aged 40 years and older
      undergoing colonoscopy for colorectal cancer screening, surveillance, or follow
      up of another abnormal screening test result. Patients were excluded if they had
      a history of inflammatory bowel disease, visible GI bleeding, or anemia. MAIN
      OUTCOME MEASURES: Incidence of minor complications and patient perceptions about
      colonoscopy. RESULTS: Minor complications occurred in 162 subjects (34%) before
      day 7 and in 29 subjects (6%) between day 7 and day 30, most commonly bloating
      (25%) and abdominal pain (11%). Six subjects had unexpected emergency department
      visits or hospitalizations within 30 days, including 2 with postpolypectomy
      bleeding. On multivariate analysis, minor complications were more common in women
      (odds ratio 1.78, 95% CI 1.21-2.62) and when the procedure lasted 20 minutes or
      longer. Bowel preparation was rated the most difficult part of the examination
      for 77%. Most subjects (94%) lost 2 or fewer days from normal activities for the
      colonoscopy itself, preparation, or recovery. CONCLUSIONS: Minor complications
      were common after screening and surveillance colonoscopy. The bowel preparation
      was the most difficult part of the examination for most patients. Most subjects
      lost 2 or fewer days from normal activities because of colonoscopy.

PMID- 17173916
TI  - Transcolonic endoscopic abdominal exploration: a NOTES survival study in a
      porcine model.
AB  - BACKGROUND: Published reports on NOTES (natural orifice transluminal endoscopic
      surgery) have thus far been limited to the transgastric method. OBJECTIVE: The
      aim of this study was to assess the transcolonic approach as a means of accessing
      and systematically exploring the abdominal cavity in a survival study design.
      DESIGN: Six pigs were placed under general anesthesia and were prepped with
      multiple tap-water enemas, followed by instillation of a cefazolin suspension and
      a povidone-iodine lavage. Equipment was prepared with a high-level chemical
      disinfection, and an aseptic technique was used. An incision was made in the
      anterior colonic wall, and abdominal exploration was performed by using a double
      channel endoscope. The incision was subsequently closed with endoscopic clips,
      endoloops, or a prototype closure device. PATIENTS: Six female Yorkshire pigs
      that weighed 25 to 30 kg. RESULTS: Stomach, liver, gallbladder, spleen, small
      bowel, colon, and peritoneal surfaces were identified in all animals in less than
      3 minutes. The lower pelvic organs were not consistently visualized. All animals
      were alive for 14 days without apparent complications. At necropsy, the colonic
      incision sites were completely closed and appeared well healed. Microscopic
      inflammatory changes were seen at the closure site in all animals, including
      microabscesses. Incision-related adhesions were identified in 4 of 6 animals.
      CONCLUSIONS: This study demonstrated the use of a novel transcolonic approach to
      successfully access and explore the abdominal cavity. In contrast to the
      transgastric method, a transcolonic approach provides more consistent
      identification of structures in the upper abdomen and provides better en face
      orientation and scope stability. Therapeutic interventions in the upper abdomen,
      including organ resection, may be more tenable by using a transcolonic method;
      however, further studies are needed to address issues of sterility and colonic
      closure.

PMID- 17173917
TI  - Endoscopic transgastric drainage of a subphrenic abscess.

PMID- 17173918
TI  - Local EUS-guided injection of chemotherapeutic agents as adjuvant to systemic
      treatment: the first steps are made.

PMID- 17173919
TI  - The bottom line: offer the colorectal cancer screening test that you can deliver.

PMID- 17173920
TI  - Estrogen therapy and brain muscarinic receptor density in healthy females: a SPET
      study.
AB  - Estrogen Therapy (ET) may protect against age-related cognitive decline and
      neuropsychiatric disorders (e.g. Alzheimer's disease). The biological basis for
      this putative neuroprotective effect is not fully understood, but may include
      modulation of cholinergic systems. Cholinergic dysfunction has been implicated in
      age-related memory impairment and Alzheimer's disease. However, to date no one
      has investigated the effect of long-term ET on brain cholinergic muscarinic
      receptor aging, and related this to cognitive function. We used Single Photon
      Emission Tomography (SPET) and (R,R)[(123)I]-I-QNB, a novel ligand with high
      affinity for m(1)/m(4) muscarinic receptors, to examine the effect of long-term
      ET and age on brain m(1)/m(4) receptors in healthy females. We included 10
      younger premenopausal subjects and 22 postmenopausal women; 11 long-term ET users
      (all treated following surgical menopause) and 11 ET never-users (surgical
      menopause, n=2). Also, verbal memory and executive function was assessed in all
      postmenopausal subjects. Compared to young women, postmenopausal women (ET users
      and never-users combined) had significantly lower muscarinic receptor density in
      all brain regions examined. ET users also had higher muscarinic receptor density
      than ET never-users in all the brain regions, and this reached statistical
      significance in left striatum and hippocampus, lateral frontal cortex and
      thalamus. Moreover, in ET users, (R,R)[(123)I]-I-QNB binding in left hippocampus
      and temporal cortex was significantly positively correlated with plasma estradiol
      levels. We also found evidence for improved executive function in ET users as
      compared to ET never-users. However, there was no significant relationship
      between receptor binding and cognitive function within any of the groups. In
      healthy postmenopausal women use of long-term ET is associated with reduced age
      related differences in muscarinic receptor binding, and this may be related to
      serum estradiol levels.

PMID- 17173921
TI  - Relationship between catheter care and catheter-associated urinary tract
      infection at Japanese general hospitals: a prospective observational study.
AB  - BACKGROUND: The risk factors for catheter-associated urinary tract infections
      (CAUTIs) that are associated with catheter care have not been examined in detail
      by prospective studies or randomised clinical trials. OBJECTIVES: To examine the
      patterns of catheter care and to identify the CAUTI risk factors associated with
      catheter care. DESIGN: Prospective observational study. METHODS: Between January
      and December 2004, 555 adult patients who were catheterised for 3 days in five
      general hospitals in Japan were surveyed. One researcher collected the following
      data twice a week: catheter insertion method, catheter management, and signs and
      symptoms of urinary tract infections. The relative risk exceeding 1 by the
      Poisson regression were selected for Cox proportional hazard analysis in order to
      calculate adjusted risks. In addition, expected reductions in the incidence of
      CAUTIs by elimination of the risk factors were estimated using the population
      attributable risk percent. RESULTS: The mean duration of catheterisation was 25
      days. The overall incidence of CAUTIs was 3.9 cases per 1000-device days; the
      incidence of CAUTIs ranged from 0.6 to 7.2 cases per 1000-device days among the
      five hospitals. Only fecal incontinent patients were analysed since they
      accounted for 94% of the CAUTI cases. In the univariate analysis, the silver
      alloy catheter, which contains antimicrobial property, emerged as a potential
      risk. Since silver-alloy catheters were used in only one hospital, silver-alloy
      catheter care was compared with that of the other types of catheter, and a
      significantly higher percentage of inappropriate care was observed. In the final
      Cox model, two variables remained: 'non-pre-connected closed system (standard
      system)' (RR 2.35, 95%CI 1.20-4.60, p = 0.013) and 'no daily cleansing of the
      perineal area' (RR 2.49, 95%CI 1.32-4.69, p = 0.005). The population attributable
      risk percent suggested that the use of a 'pre-connected closed system' and 'daily
      cleansing of the perineal area' could reduce the incidence of CAUTIs by nearly
      50%. CONCLUSIONS: Our investigation identified fecal incontinence as the major
      risk factor for CAUTIs in the study population. However, attributable risk
      percent indicates that the implementation of two basic elements of catheter care
      could reduce CAUTIs by nearly 50%. The hospital using silver-alloy catheters had
      the highest CAUTI rates, strongly suggesting the hazards of relying on the
      antimicrobial property of silver and the resultant laxity in care.

PMID- 17173922
TI  - The knowledgeable practice of critical care nurses: a poststructural inquiry.
AB  - BACKGROUND: Contemporary nursing literature emphasises the desirability of
      clinical nurses being "knowledgeable". However, the need for nurses constantly to
      acquire more knowledge is reiterated. Lack of knowledge is seen to underlie an
      array of professional problems. Little is known of how nurses themselves
      understand what it means to practise knowledgeably. OBJECTIVE: To explore
      critical care nurses' understandings of knowledgeable practice and its
      relationship to being a "good nurse". METHODOLOGY: A poststructuralist framework
      informed the study. The study participants were 12 critical care nurses. Data
      were generated through three individual focused interviews with each participant.
      Data analysis involved deconstruction of the interview texts to reveal
      participants' discourses of knowledgeable practice and the implications of these
      discourses for their subjectivity and for their work. FINDINGS: A discourse of
      knowledgeable practice was revealed as central to participants' sense of identity
      as "good nurses". Participants believed their knowledge resided in their heads
      ("knowing why") and in their hands ("knowing how"). Fluency of action, which was
      achieved and maintained by frequent repetition of activities, contributed to
      their sense of being knowledgeable. Participants described being excluded from
      knowledge in some instances. In general, however, "actual" knowledge was of less
      importance than was being positioned, by themselves and others, as knowledgeable.
      This positioning was frequently undermined by other staff, both medical and
      nursing. Analysis revealed that the discourse of knowledgeable practice was
      underpinned by a dichotomy of ignorant/knowledgeable, in which "ignorant" was the
      dominant category; hence, nurses were assumed to be ignorant until they could
      "prove" otherwise. CONCLUSIONS: The findings contest the notion, espoused in
      nursing literature, that acquisition of knowledge can "empower" nurses, thus
      providing the solution to problems they may experience. Rather, strategies are
      required that challenge and disrupt relations of power that construct nurses as
      "ignorant".

PMID- 17173923
TI  - Differential role and tissue specificity of interleukin-1alpha gene expression in
      atherogenesis and lipid metabolism.
AB  - OBJECTIVE: We examined the role of IL-1alpha and IL-1beta expressed by bone
      marrow-derived cells in atherogenesis and lipid metabolism. METHODS AND RESULTS:
      We first studied the effect of atherogenic diet on wild-type C57BL/6 IL-1alpha or
      IL-1beta deficient mice. IL-1alpha KO resulted in a comparatively higher total
      cholesterol levels, compared to WT and IL-1beta KO mice (398+/-10; 266+/-19;
      223+/-13 mg/dl, respectively, p<0.001), due to higher non-HDL cholesterol.
      Nevertheless, aortic sinus lesion area was 56% lower in IL-1alpha KO (p<0.05) and
      50% lower in IL-1beta KO (p=0.08), compared to WT mice. Likewise, SAA levels in
      IL-1alpha KO mice were markedly lower compared to WT and IL-1beta KO mice (31+/
      14; 220+/-33 and 106+/-39 microg/ml, respectively, p<0.001). To study the
      specific role of bone marrow-derived IL-1, irradiated C57BL/6 mice were
      transplanted with either IL-1+/+, IL-1alpha-/- or IL-1beta-/- bone marrow cells.
      Despite similar lipoprotein levels, aortic sinus lesion area was 59% lower in IL
      1alpha-/- transplanted (p<0.05) compared to IL-1+/+ transplanted mice. Lesion
      area in IL-1beta-/- was 33% lower than in IL-1+/+ recipient mice, but it was not
      statistically significant. CONCLUSION: We demonstrated that early lesion
      formation is accelerated specifically by bone marrow-derived IL-1alpha.
      Furthermore, we showed that the expression of IL-1alpha in cells other than the
      bone marrow plays a significant role in non-HDL cholesterol metabolism.

PMID- 17173924
TI  - Predictive value of white blood cell subtypes for long-term outcome following
      myocardial infarction.
AB  - INTRODUCTION: Elevation of total white blood cells (WBC) count is associated with
      higher mortality in patients with acute coronary syndromes. However, it is
      unknown which specific subset of leukocytes best correlates with increased risk
      of adverse outcome. METHODS AND RESULTS: We prospectively studied the predictive
      value of WBC subtypes for long-term outcome in 1037 patients with acute
      myocardial infarction (AMI). Total WBC, neutrophil, monocyte and lymphocyte
      counts, and high-sensitivity C-reactive protein (CRP) were obtained in each
      patient. The median duration of follow up was 23 months (range, 6-42 months).
      Analyzed separately, baseline total WBC (HR 2.2, 95% CI 1.5-3.3; P<0.0001),
      neutrophil (HR 2.7, 95% CI 1.8-4.1; P<0.0001) and monocyte (HR 1.9, 95% CI 1.3
      2.8; P=0.001) counts in the upper quartile, and lymphocyte count in the lower
      quartile (HR 1.5, 95% CI 1.1-2.3; P=0.03), were all independent predictors of
      mortality. Comparing nested models, adding other WBC data failed to improve model
      based on neutrophil count. In contrast, adding neutrophil count to the models
      based on total WBC (P=0.01), on monocyte count (P<0.0001) or on lymphocyte count
      (P<0.0001) improved the prediction of the models. Neutrophil count in the upper
      quartile (>or=9800 microL(-1)) remained a strong independent predictor of
      mortality after adjustment for left ventricular systolic function and for CRP (HR
      2.2, 95% CI 1.6-3.0; P<0.0001). CONCLUSION: Of all WBC subtypes, elevated
      neutrophil count best correlates with mortality in patients with AMI. Neutrophil
      count provides additive prognostic information when combined with CRP.

PMID- 17173925
TI  - Random-walk models of cell dispersal included in mechanobiological simulations of
      tissue differentiation.
AB  - Computational models have shown that biophysical stimuli can be correlated with
      observed patterns of tissue differentiation, and simulations have been performed
      that predict the time course of tissue differentiation in, for example, long bone
      fracture healing. Some simulations have used a diffusion model to simulate the
      migration and proliferation of cells with the differentiating tissue. However,
      despite the convenience of the diffusion model, diffusion is not the mechanism of
      cell dispersal: cells disperse by crawling or proliferation, or are transported
      in a moving fluid. In this paper, a random-walk model (i.e., a stochastic model),
      with and without a preferred direction, is studied as an approach to simulate
      cell proliferation/migration in differentiating tissues and it is compared with
      the diffusion model. A simulation of tissue differentiation of gap tissue in a
      two-dimensional model of a bone/implant interface was performed to demonstrate
      the differences between diffusion vs. random walk with a preferred direction.
      Results of diffusion and random-walk models are similar with respect to the
      change in the stiffness of the gap tissue but rather different results are
      obtained regarding tissue patterning in the differentiating tissues; the
      diffusion approach predicted continuous patterns of tissue differentiation
      whereas the random-walk model showed a more discontinuous pattern-histological
      results are not available that can unequivocally establish which is most similar
      to experimental observation. Comparing isotropic to anisotropic random walk
      (preferred direction of proliferation and cell migration), a more rapid reduction
      of the relative displacement between implant and bone is predicted. In
      conclusion, we have shown how random-walk models of cell dispersal and
      proliferation can be implemented, and shown where differences between them exist.
      Further study of the random-walk model is warranted, given the importance of cell
      seeding and cell dispersal/proliferation in many mechanobiological problems.

PMID- 17173926
TI  - Detecting naphthenic acids in waters by gas chromatography-mass spectrometry.
AB  - Naphthenic acids (general formula C(n)H(2n+Z)O(2)) are water-soluble, toxic
      compounds found in petroleum and bitumen. Some of the current methods for
      detecting these acids in waters depend on measuring the presence of the
      carboxylic acid functional group, and therefore many of these methods also detect
      naturally occurring carboxylic acids that are not naphthenic acids. We report a
      procedure that includes liquid-liquid extraction, cleanup, and derivatization to
      form t-butyldimethylsilyl esters prior to gas chromatography-mass spectrometry
      (GC-MS) analysis. Using low- and high-resolution MS to detect the ion
      C(15)H(27)O(2)Si(+) (nominal m/z=267) is an excellent indicator of the presence
      of naphthenic acids at concentrations > or =10microgL(-1).

PMID- 17173927
TI  - Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha
      chain (CD127), allowing consistent identification and sorting of live cells.
AB  - Although quantitative identification and viable enrichment of natural regulatory
      T cells (T-regs) in humans are problematic, such steps would greatly facilitate
      the analysis of these cells in disease states. In an attempt to identify markers
      that are sensitive and specific for human T-regs, we analyzed the expression of
      fourteen intracellular and cell surface markers on human CD4(+) cells. Many
      markers were partially selective for CD25(hi) T-regs, but consistent and specific
      discrimination of functional T-regs was only made possible by focus on CD127, the
      alpha chain of the IL-7 receptor. Although most CD4(+) human T cells express
      CD127, T-regs exhibiting suppressive activity in vitro display distinctly lower
      surface expression of this marker, irrespective of their level of CD25
      expression. Sorted cells with the surface phenotype CD4(+)CD25(+)CD127(low) had
      higher levels of intracellular FOXP3 and CTLA-4 and, as determined by functional
      assays, were suppressive, hypoproliferative, and poorly responsive to TCR
      signaling. The CD4(+)CD25(+)CD127(low) phenotype was also found to be
      characteristic of T-regs found in mice and in rhesus macaques. This surface
      phenotype should allow for quantitative studies of regulatory T cells in disease
      states as well as for enrichment of live regulatory T cells for functional
      analyses and/or expansion in vitro.

PMID- 17173930
TI  - Dimerization of the erythropoietin receptor transmembrane domain in micelles.
AB  - Erythropoietin receptor (EpoR) homodimerization is an initial regulatory step in
      erythrocyte formation. Receptor dimers form before ligand binding, suggesting
      that association between receptor proteins is dependent on the receptor itself.
      EpoR dimerization is an essential step in erythropoiesis, and misregulation of
      this dimerization has been implicated in several disease states, including multi
      lineage leukemias; nevertheless, how EpoR regulates its own dimerization is
      unclear. In vivo experiments suggest the single-pass transmembrane helix is the
      strongest candidate for driving ligand-independent association. To address the
      self-association potential of this transmembrane segment, we studied its
      interaction energetics in micelles by utilizing a previously successful
      Staphylococcal nuclease (SN-EpoR TM) fusion protein. This fusion protein strategy
      allows expression of the EpoR transmembrane domain in Escherichia coli
      independent of the other EpoR domains. Sedimentation equilibrium analytical
      ultracentrifugation of the detergent-solubilized SN-EpoR TM demonstrated that the
      murine EpoR transmembrane domain self-associates to form dimers. Although this
      interaction is not as stable as the dimerization of the well-studied glycophorin
      A transmembrane dimer, the murine EpoR transmembrane domain dimer is more stable
      than the interactions of the colon carcinoma kinase 4 transmembrane domain. The
      same experiments with the human EpoR transmembrane domain, which differs from the
      mouse sequence by only three residues, revealed a less favorable interaction than
      that of the murine sequence and is only slightly more favorable than that
      expected for non-preferential binding. These results suggest that the mouse and
      human receptor proteins may differ in the roles they play in signaling.

PMID- 17173928
TI  - Crystal structure of lactaldehyde dehydrogenase from Escherichia coli and
      inferences regarding substrate and cofactor specificity.
AB  - Aldehyde dehydrogenases catalyze the oxidation of aldehyde substrates to the
      corresponding carboxylic acids. Lactaldehyde dehydrogenase from Escherichia coli
      (aldA gene product, P25553) is an NAD(+)-dependent enzyme implicated in the
      metabolism of l-fucose and l-rhamnose. During the heterologous expression and
      purification of taxadiene synthase from the Pacific yew, lactaldehyde
      dehydrogenase from E. coli was identified as a minor (</=5%) side-product
      subsequent to its unexpected crystallization. Accordingly, we now report the
      serendipitous crystal structure determination of unliganded lactaldehyde
      dehydrogenase from E. coli determined by the technique of multiple isomorphous
      replacement using anomalous scattering at 2.2 A resolution. Additionally, we
      report the crystal structure of the ternary enzyme complex with products lactate
      and NADH at 2.1 A resolution, and the crystal structure of the enzyme complex
      with NADPH at 2.7 A resolution. The structure of the ternary complex reveals that
      the nicotinamide ring of the cofactor is disordered between two conformations:
      one with the ring positioned in the active site in the so-called hydrolysis
      conformation, and another with the ring extended out of the active site into the
      solvent region, designated the out conformation. This represents the first
      crystal structure of an aldehyde dehydrogenase-product complex. The active site
      pocket in which lactate binds is more constricted than that of medium-chain
      dehydrogenases such as the YdcW gene product of E. coli. The structure of the
      binary complex with NADPH reveals the first view of the structural basis of
      specificity for NADH: the negatively charged carboxylate group of E179
      destabilizes the binding of the 2'-phosphate group of NADPH sterically and
      electrostatically, thereby accounting for the lack of enzyme activity with this
      cofactor.

PMID- 17173931
TI  - Intermolecular interactions and characterization of the novel factor Xa exosite
      involved in macromolecular recognition and inhibition: crystal structure of human
      Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the
      hematophagous nematode Ancylostoma caninum.
AB  - NAPc2, an anticoagulant protein from the hematophagous nematode Ancylostoma
      caninum evaluated in phase-II/IIa clinical trials, inhibits the extrinsic blood
      coagulation pathway by a two step mechanism, initially interacting with the
      hitherto uncharacterized factor Xa exosite involved in macromolecular recognition
      and subsequently inhibiting factor VIIa (K(i)=8.4 pM) of the factor VIIa/tissue
      factor complex. NAPc2 is highly flexible, becoming partially ordered and
      undergoing significant structural changes in the C terminus upon binding to the
      factor Xa exosite. In the crystal structure of the ternary factor
      Xa/NAPc2/selectide complex, the binding interface consists of an intermolecular
      antiparallel beta-sheet formed by the segment of the polypeptide chain consisting
      of residues 74-80 of NAPc2 with the residues 86-93 of factor Xa that is
      additional maintained by contacts between the short helical segment (residues 67
      73) and a turn (residues 26-29) of NAPc2 with the short C-terminal helix of
      factor Xa (residues 233-243). This exosite is physiologically highly relevant for
      the recognition and inhibition of factor X/Xa by macromolecular substrates and
      provides a structural motif for the development of a new class of inhibitors for
      the treatment of deep vein thrombosis and angioplasty.

PMID- 17173932
TI  - In vitro manipulation of cleft palate connective tissue: setting the bases of a
      proposed new treatment.
AB  - BACKGROUND: Palatoplasty has the undesired side effect of impaired mid-facial
      growth. To avoid this problem, we propose an alternative to palatoplasty. We
      hypothesize that if BMP-2 is injected together with a carrier into the periosteum
      of the cleft palate borders, border volume will increase and connective tissue
      cells will be activated to produce extra bone. Once these borders supported by
      bone reach the midline, extraction of their covering epithelia with trypsin will
      permit adhesion of the underlying tissues. We investigated in vitro the ability
      of cleft palate connective tissue cells to produce extra bone in the presence of
      BMP-2 and the possibility of using trypsin to remove the epithelium covering the
      cleft palate borders without impairing the underlying tissues' ability to adhere.
      MATERIALS AND METHODS: We used the cleft palate presented by tgf-beta(3) null
      mice and small fragments of human cleft palate mucoperiosteum as models.
      Immunolabeling BMP-2-treated or untreated cultures with TUNEL and anti
      osteocalcin or PCNA antibodies was performed. The epithelium of the cleft palate
      borders was removed with a trypsin solution, and the de-epithelialized tissues
      were cultured in apposition. RESULTS: BMP-2 induces differentiation toward bone
      on cleft palate connective tissue cells without producing cell death or
      proliferation. Trypsin removal of the cleft palate margins' epithelium does not
      impair the underlying tissues' adhesion. CONCLUSION: It is possible to generate
      extra bone at the cleft palate margins and to chemically eliminate their covering
      epithelia without damaging the underlying tissues, which allows further
      investigation in vivo of this new approach for cleft palate closure.

PMID- 17173929
TI  - How regulators of G protein signaling achieve selective regulation.
AB  - The regulators of G protein signaling (RGS) are a family of cellular proteins
      that play an essential regulatory role in G protein-mediated signal transduction.
      There are multiple RGS subfamilies consisting of over 20 different RGS proteins.
      They are basically the guanosine triphosphatase (GTPase)-accelerating proteins
      that specifically interact with G protein alpha subunits. RGS proteins display
      remarkable selectivity and specificity in their regulation of receptors, ion
      channels, and other G protein-mediated physiological events. The molecular and
      cellular mechanisms underlying such selectivity are complex and cooperate at many
      different levels. Recent research data have provided strong evidence that the
      spatiotemporal-specific expression of RGS proteins and their target components,
      as well as the specific protein-protein recognition and interaction through their
      characteristic structural domains and functional motifs, are determinants for RGS
      selectivity and specificity. Other molecular mechanisms, such as alternative
      splicing and scaffold proteins, also significantly contribute to RGS selectivity.
      To pursue a thorough understanding of the mechanisms of RGS selective regulation
      will be of great significance for the advancement of our knowledge of molecular
      and cellular signal transduction.

PMID- 17173933
TI  - Perflubron emulsion prevents PMN activation and improves myocardial functional
      recovery after cold ischemia and reperfusion.
AB  - BACKGROUND: In cardiopulmonary bypass, extracorporeal circulation activates
      neutrophils, which contribute to ischemia reperfusion injury and postoperative
      myocardial dysfunction. Perfluorocarbons (PFCs) are compounds that dissolve
      oxygen and have anti-inflammatory and neutrophil-stabilizing properties. We
      hypothesized that perflubron emulsion (PFE), a PFC, would attenuate neutrophil
      activation during simulated extracorporeal circulation (SECC) and would preserve
      myocardial functional recovery during reperfusion after cold ischemia. METHODS:
      In a SECC, diluted blood was circulated for 120 min and subsequently used to
      reperfuse isolated rat hearts after 2 h of cold (12 degrees C) ischemia. Three
      groups were studied: noncirculated control; SECC/no additive; and SECC/PFE added.
      In control and SECC/no additive groups, whole blood was diluted 1:1 with
      plasmalyte. SECC/PFE blood was diluted 1:1 with plasmalyte and PFE (0.075 mL/mL
      diluted whole blood). Blood counts and neutrophil activation experiments were
      performed before and after 120 min of SECC. Reperfusion was accomplished using a
      modified Langendorff preparation. Left ventricular developed pressure, dP/dt, and
      coronary flow were measured at 10, 15, and 20 min of reperfusion. RESULTS: After
      120 min SECC, neutrophil activation was significantly reduced in the SECC/PFE
      group compared to the SECC/no additive group (38.1 +/- 2.3% versus 51.7 +/- 1.0%,
      P < 0.05). Compared to cold ischemic hearts reperfused with fresh, non
      recirculated blood, left ventricular developed pressure and dP/dt were
      significantly impaired in the cold ischemic hearts reperfused with SECC/no
      additive blood (P < 0.05). In contrast, myocardial functional recovery was not
      impaired in the hearts reperfused with SECC/PFE blood. CONCLUSIONS: SECC-induced
      neutrophil activation was attenuated with Perflubron treatment. In addition, the
      progressive impairment in myocardial functional recovery after cold ischemia was
      significantly improved with treatment. PFE has clinical potential to limit
      neutrophil-mediated reperfusion injury following cold ischemia.

PMID- 17173934
TI  - Cardiovascular and cerebrovascular responses to lower body negative pressure in
      type 2 diabetic patients.
AB  - In diabetic patients, vascular disease and autonomic dysfunction might compromise
      cerebral autoregulation and contribute to orthostatic intolerance. The aim of our
      study was to determine whether impaired cerebral autoregulation contributes to
      orthostatic intolerance during lower body negative pressure in diabetic patients.
      Thirteen patients with early-stage type 2 diabetes were studied. We continuously
      recorded RR-interval, mean blood pressure and mean middle cerebral artery blood
      flow velocity at rest and during lower body negative pressure applied at -20 and 
      40 mm Hg. Spectral powers of RR-interval, blood pressure and cerebral blood flow
      velocity were analyzed in the sympathetically mediated low (LF: 0.04-0.15 Hz) and
      the high (HF: 0.15-0.5 Hz) frequency ranges. Cerebral autoregulation was assessed
      from the transfer function gain and phase shift between LF oscillations of blood
      pressure and cerebral blood flow velocity. In the diabetic patients, lower body
      negative pressure decreased the RR-interval, i.e. increased heart rate, while
      blood pressure and cerebral blood flow velocity decreased. Transfer function gain
      and phase shift remained stable. Lower body negative pressure did not induce the
      normal increase in sympathetically mediated LF-powers of blood pressure and
      cerebral blood flow velocity in our patients indicating sympathetic dysfunction.
      The stable phase shift, however, suggests intact cerebral autoregulation. The
      dying back pathology in diabetic neuropathy may explain an earlier and greater
      impairment of peripheral vasomotor than cerebrovascular control, thus maintaining
      cerebral blood flow constant and protecting patients from symptoms of presyncope.

PMID- 17173935
TI  - Sustained oscillations via coherence resonance in SIR.
AB  - Sustained oscillations in a stochastic SIR model are studied using a new multiple
      scale analysis. It captures the interaction of the deterministic and stochastic
      elements together with the separation of time scales inherent in the appearance
      of these dynamics. The nearly regular fluctuations in the infected and
      susceptible populations are described via an explicit construction of a
      stochastic amplitude equation. The agreement between the power spectral densities
      of the full model and the approximation verifies that coherence resonance is
      driving the behavior. The validity criteria for this asymptotic approximation
      give explicit expressions for the parameter ranges in which one expects to
      observe this phenomenon.

PMID- 17173936
TI  - Sex difference in norepinephrine surge in response to psychological stress
      through nitric oxide in rats.
AB  - Psychological stress elevates blood pressure through sympathetic nerve
      activation. This pressor response is supposedly associated with cardiovascular
      events. We investigated a sex difference in the pressor response and
      norepinephrine surge to cage-switch stress in rats. Wistar male and female rats
      were catheterized for blood pressure monitoring and blood sampling. Six days post
      surgery, the rats were exposed to the cage-switch stress and blood samples were
      collected at rest and 30 min after the start of the stress. The stress-induced
      pressor response was greater in the male than in the female rats. The stress
      significantly increased the norepinephrine level in the male, but not in the
      female rats. Pre-treatment with N(G)-nitro-l-arginine methyl ester (L-NAME), a
      nitric oxide (NO) synthase inhibitor, attenuated the norepinephrine response
      significantly in the male rats. There was no sex difference in the endothelial NO
      synthase expression in the gastrocnemius muscle. However the phosphorylation at
      serine 1177, a marker for eNOS activation, was higher in the male than in the
      female rats. These results suggest that NO is involved in the norepinephrine
      surge to psychological stress in the male rats, but not in the female rats. This
      is the first report on a sex difference in the norepinephrine surge in response
      to psychological stress through NO, in association with pressor response.

PMID- 17173937
TI  - Neurochemical effects of the endocannabinoid uptake inhibitor UCM707 in various
      rat brain regions.
AB  - To date, UCM707, (5Z,8Z,11Z,14Z)-N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide,
      has the highest potency and selectivity in vitro and in vivo as inhibitor of the
      endocannabinoid uptake. Its biochemical, pharmacological and therapeutic
      properties have been intensely studied recently, but the information on its
      capability to modify neurotransmitter activity, which obviously underlies the
      above properties, is still limited. In the present study, we conducted a time
      course experiment in rats aimed at examining the neurochemical effects of UCM707
      in several brain regions following a subchronic administration (5 injections
      during 2.5 days) of this inhibitor in a dose of 5 mg/kg weight. In the
      hypothalamus, the administration of UCM707 did not modify GABA contents but
      reduced norepinephrine levels at 5 h after administration, followed by an
      increase at 12 h. Similar trends were observed for dopamine, whereas serotonin
      content remained elevated at 1 and, in particular, 5 and 12 h after
      administration. In the case of the basal ganglia, UCM707 reduced GABA content in
      the substantia nigra but only at longer (5 or 12 h) times after administration.
      There were no changes in serotonin content, but a marked reduction in its
      metabolite 5HIAA was recorded in the substantia nigra. The same pattern was found
      for dopamine, contents of which were not altered by UCM707 in the caudate
      putamen, but its major metabolite DOPAC exhibited a marked decrease at 5 h. In
      the cerebellum, UCM707 reduced GABA, serotonin and norepinephrine content, but
      only the reduction found for norepinephrine at 5 h reached statistical
      significance. The administration of UCM707 did not modify the contents of these
      neurotransmitters in the hippocampus and the frontal cortex. Lastly, in the case
      of limbic structures, the administration of UCM707 markedly reduced dopamine
      content in the nucleus accumbens at 5 h, whereas GABA content remained unchanged
      in this structure and also in the ventral-tegmental area and the amygdala. By
      contrast, norepinephrine and serotonin content increased at 5 h in the nucleus
      accumbens, but not in the other two limbic structures. In summary, UCM707
      administered subchronically modified the contents of serotonin, GABA, dopamine
      and/or norepinephrine with a pattern strongly different in each brain region. So,
      changes in GABA transmission (decrease) were restricted to the substantia nigra,
      but did not appear in other regions, whereas dopamine transmission was also
      altered in the caudate-putamen and the nucleus accumbens. By contrast,
      norepinephrine and serotonin were altered by UCM707 in the hypothalamus,
      cerebellum (only norepinephrine), and nucleus accumbens, exhibiting biphasic
      effects in some cases.

PMID- 17173938
TI  - Impacts of gold mine waste disposal on deepwater fish in a pristine tropical
      marine system.
AB  - Little is known about the impacts of mine waste disposal, including deep-sea
      tailings, on tropical marine environments and this study presents the first
      account of this impact on deepwater fish communities. The Lihir gold mine in
      Papua New Guinea has deposited both excavated overburden and processed tailings
      slurry into the coastal environment since 1997. The abundances of fish species
      and trace metal concentrations in their tissues were compared between sites
      adjacent to and away from the mine. In this study (1999-2002), 975 fish of 98
      species were caught. Significantly fewer fish were caught close to the mine than
      in neighbouring regions; the highest numbers were in regions distant from the
      mine. The catch rates of nine of the 17 most abundant species were lowest, and in
      three species were highest, close to the mine. There appears to be limited
      contamination in fish tissues caused by trace metals disposed as mine waste.
      Although arsenic (several species) and mercury (one species) were found in
      concentrations above Australian food standards. However, as in the baseline (pre
      mine) sampling, it appears they are accumulating these metals mostly from
      naturally-occurring sources rather than the mine waste.

PMID- 17173939
TI  - Some properties of a simple stochastic epidemic model of SIR type.
AB  - We investigate the properties of a simple discrete time stochastic epidemic
      model. The model is Markovian of the SIR type in which the total population is
      constant and individuals meet a random number of other individuals at each time
      step. Individuals remain infectious for R time units, after which they become
      removed or immune. Individual transition probabilities from susceptible to
      diseased states are given in terms of the binomial distribution. An expression is
      given for the probability that any individuals beyond those initially infected
      become diseased. In the model with a finite recovery time R, simulations reveal
      large variability in both the total number of infected individuals and in the
      total duration of the epidemic, even when the variability in number of contacts
      per day is small. In the case of no recovery, R=infinity, a formal diffusion
      approximation is obtained for the number infected. The mean for the diffusion
      process can be approximated by a logistic which is more accurate for larger
      contact rates or faster developing epidemics. For finite R we then proceed mainly
      by simulation and investigate in the mean the effects of varying the parameters p
      (the probability of transmission), R, and the number of contacts per day per
      individual. A scale invariant property is noted for the size of an outbreak in
      relation to the total population size. Most notable are the existence of maxima
      in the duration of an epidemic as a function of R and the extremely large
      differences in the sizes of outbreaks which can occur for small changes in R.
      These findings have practical applications in controlling the size and duration
      of epidemics and hence reducing their human and economic costs.

PMID- 17173940
TI  - ent-Abietane diterpenoids from Isodon rubescens var. rubescens.
AB  - ent-Abietane diterpenoids, hebeiabinins A-F (1-5), together with seven known
      diterpenoids were isolated from leaves of Isodon rubescens var. rubescens. The
      structures of 1-5 were established on the basis of spectroscopic analyses,
      including application of 2D NMR spectroscopic techniques. The diterpenoids
      isolated were evaluated for the cytotoxicity against A549, HT-29, and K562 tumor
      cells. Compound 5 was the most active with IC(50) value of 0.91 microM against
      A549 cells.

PMID- 17173941
TI  - Linkage of progestin and epidermal growth factor signaling: phosphorylation of
      progesterone receptors mediates transcriptional hypersensitivity and increased
      ligand-independent breast cancer cell growth.
AB  - Progesterone receptor (PR) action is linked to epidermal growth factor (EGF)
      initiated signaling pathways at multiple levels; mitogen-activated protein
      kinases (MAPKs) are key mediators of this important cross-talk. Herein, we probed
      the effects of EGF on PR function and regulation of breast cancer cell growth.
      EGF stimulated rapid and transient phosphorylation of PR-B Ser294 relative to
      persistent phosphorylation of this site induced by the synthetic progestin,
      R5020. EGF induced nuclear translocation and DNA binding of unliganded wild-type,
      but not mutant PRs containing an Ala at position 294 (S294A). However, EGF alone
      induced little to no PR-B transcriptional activity; S294A PR-B was
      transcriptionally impaired. In contrast, pretreatment of cells with EGF (30min)
      significantly increased the potency and efficacy of wild-type, but not S294A PR
      transcriptional activity in response to progestin, and enhanced ligand-dependent
      downregulation of wild-type but not S294A PR. Replacement of Ser294 with aspartic
      acid (S294D) to mimic phosphorylation at this site decreased receptor stability
      and, as predicted, heightened progestin-induced transcription relative to wild
      type PR-B. RT-PCR demonstrated the Ser294 phosphorylation-dependence of selected
      PR target genes (TGFalpha and HB-EGF). Surprisingly, PR-B expressing cells
      growing in soft agar were highly responsive to EGF or progestin, and this was
      further stimulated by the combination of both hormones. Cells expressing S294A PR
      exhibited reduced soft agar growth, and were also sensitive to R5020 alone, but
      failed to respond to EGF. These results suggest that PR Ser294 is an important
      "sensor" for growth factor inputs that affects PR function and breast cancer cell
      growth in the absence of progestin or in the presence of low or "sub-threshold"
      progestin concentrations. PR function likely contributes to breast cancer
      progression when EGFR family members or their ligands are overexpressed, a
      condition that predicts low abundance, but highly active and nuclear PR.

PMID- 17173943
TI  - Phosphate uptake in chick kidney cells: effects of 1,25(OH)2D3 and 24,25(OH)2D3.
AB  - Phosphate homeostasis is controlled in part by absorption from the intestine, and
      reabsorption in the kidney. While the effect of Vitamin D metabolites on
      enterocytes is well documented, in the current study we assess selected responses
      in primary cultures of kidney cells. Time course studies revealed a rapid
      stimulation of phosphate uptake in cells treated with 1,25(OH)(2)D(3), relative
      to controls. Dose-response studies indicated a biphasic curve with optimal
      stimulation at 300 pM 1,25(OH)(2)D(3) and inhibition at 600 pM seco-steroid.
      Antibody 099--against the 1,25D(3)-MARRS receptor - abolished stimulation by the
      steroid hormone. Moreover, phosphate uptake was mediated by the protein kinase C
      pathway. The metabolite 24,25(OH)(2)D(3), which was found to inhibit the rapid
      stimulation of phosphate uptake in intestinal cells, had a parallel effect in
      cultured kidney cells. Finally, the 24,25(OH)(2)D(3) binding protein, catalase,
      was assessed for longer term down regulation. In both intestinal epithelial cells
      and kidney cells incubated with 24,25(OH)(2)D(3) for 5-24h, both the specific
      activity of the enzyme and protein levels were decreased relative to controls,
      while 1,25(OH)(2)D(3) increased both parameters over the same time periods. We
      conclude that the Vitamin D metabolites have similar effects in both kidney and
      intestine, and that 24,25(OH)(2)D(3) may have effects at the level of gene
      expression.

PMID- 17173942
TI  - Transit of hormonal and EGF receptor-dependent signals through cholesterol-rich
      membranes.
AB  - The functional consequences of changes in membrane lipid composition that
      coincide with malignant growth are poorly understood. Sufficient data have been
      acquired from studies of lipid binding proteins, post-translational modifications
      of signaling proteins, and biochemical inhibition of lipidogenic pathways to
      indicate that growth and survival pathways might be substantially re-directed by
      alterations in the lipid content of membranes. Cholesterol and glycosphingolipids
      segregate into membrane patches that exhibit a liquid-ordered state in comparison
      to membrane domains containing relatively lower amounts of these classes of
      lipids. These "lipid raft" structures, which may vary in size and stability in
      different cell types, both accumulate and exclude signaling proteins and have
      been implicated in signal transduction through a number of cancer-relevant
      pathways. In prostate cancer cells, signaling from epidermal growth factor
      receptor (EGFR) to the serine-threonine kinase Akt1, as well as from IL-6 to
      STAT3, have been demonstrated to be influenced by experimental interventions that
      target cholesterol homeostasis. The recent finding that classical steroid hormone
      receptors also reside in these microdomains, and thus may function within these
      structures in a signaling capacity independent of their role as nuclear factors,
      suggests a novel means of cross-talk between receptor tyrosine kinase-derived and
      steroidogenic signals. Potential points of intersection between components of the
      EGFR family of receptor tyrosine kinases and androgen receptor signaling
      pathways, which may be sensitive to disruptions in cholesterol metabolism, are
      discussed. Understanding the manner in which these pathways converge within
      cholesterol-rich membranes may present new avenues for therapeutic intervention
      in hormone-dependent cancers.

PMID- 17173944
TI  - The influence of water mixtures on the dermal absorption of glycol ethers.
AB  - Glycol ethers are solvents widely used alone and as mixtures in industrial and
      household products. Some glycol ethers have been shown to have a range of toxic
      effects in humans following absorption and metabolism to their aldehyde and acid
      metabolites. This study assessed the influence of water mixtures on the dermal
      absorption of butoxyethanol and ethoxyethanol in vitro through human skin.
      Butoxyethanol penetrated human skin up to sixfold more rapidly from aqueous
      solution (50%, 450 mg/ml) than from the neat solvent. Similarly penetration of
      ethoxyethanol was increased threefold in the presence of water (50%, 697 mg/ml).
      There was a corresponding increase in apparent permeability coefficient as the
      glycol ether concentration in water decreased. The maximum penetration rate of
      water also increased in the presence of both glycol ethers. Absorption through a
      synthetic membrane obeyed Fick's Law and absorption through rat skin showed a
      similar profile to human skin but with a lesser effect. The mechanisms for this
      phenomenon involves disruption of the stratum corneum lipid bilayer by
      desiccation by neat glycol ether micelles, hydration with water mixtures and the
      physicochemical properties of the glycol ether-water mixtures. Full elucidation
      of the profile of absorption of glycol ethers from mixtures is required for risk
      assessment of dermal exposure. This work supports the view that risk assessments
      for dermal contact scenarios should ideally be based on absorption data obtained
      for the relevant formulation or mixture and exposure scenario and that absorption
      derived from permeability coefficients may be inappropriate for water-miscible
      solvents.

PMID- 17173945
TI  - Arsenic methylation capability and hypertension risk in subjects living in
      arseniasis-hyperendemic areas in southwestern Taiwan.
AB  - BACKGROUND: Cumulative arsenic exposure (CAE) from drinking water has been shown
      to be associated with hypertension in a dose-response pattern. This study further
      explored the association between arsenic methylation capability and hypertension
      risk among residents of arseniasis-hyperendemic areas in Taiwan considering the
      effect of CAE and other potential confounders. METHOD: There were 871 subjects
      (488 women and 383 men) and among them 372 were diagnosed as having hypertension
      based on a positive history or measured systolic blood pressure >or=140 mm Hg
      and/or diastolic blood pressure >or=90 mm Hg. Urinary arsenic species were
      determined by high-performance liquid chromatography-hydride generator and atomic
      absorption spectrometry. Primary arsenic methylation index [PMI, defined as
      monomethylarsonic acid (MMA(V)) divided by (As(III)+As(V))] and secondary arsenic
      methylation index (SMI, defined as dimethylarsinic acid divided by MMA(V)) were
      used as indicators for arsenic methylation capability. RESULTS: The level of
      urinary arsenic was still significantly correlated with cumulative arsenic
      exposure (CAE) calculated from a questionnaire interview (p=0.02) even after the
      residents stopped drinking the artesian well water for 2-3 decades. Hypertensive
      subjects had higher percentages of MMA(V) and lower SMI than subjects without
      hypertension. However, subjects having CAE >0 mg/L-year had higher hypertension
      risk than those who had CAE=0 mg/L-year disregard a high or low methylation
      index. CONCLUSION: Inefficient arsenic methylation ability may be related with
      hypertension risk.

PMID- 17173946
TI  - The effect of ultrasonic irradiation on doxorubicin-induced cytotoxicity in three
      human bladder cancer cell lines.
AB  - Although ultrasonic irradiation has been proven to increase membrane permeability
      and enhance chemotherapeutic cytotoxicity in a number of cell lines, this effect
      has never been demonstrated in bladder cancer cells. Bladder cancer may offer a
      unique setting for ultrasound enhancement of chemotherapy, since intravesicular
      rather than intravenous administration of chemotherapy is used in superficial
      cases. The aim of this study was to investigate whether a non-toxic dose of
      ultrasound could increase membrane permeability, and potentiate the cytotoxicity
      of doxorubicin to three human bladder carcinoma cell lines (TCC-SUP, T24, and
      RT4) in vitro. An EuTDA-Efflux assay, which measures the amount of a chemical
      that is allowed to seep out of labeled cells, was used to analyze membrane
      permeability, and an MTS assay, which directly measures cell viability, was used
      to determine the effect of chemotherapy on cells after they were treated with a
      variety of doxorubicin concentrations and ultrasonic exposures. Ultrasound
      treatment for 5min and 10min at an intensity of approximately 0.3W/cm(2) resulted
      in a significant increase in EuTDA efflux in all three cell lines. However, no
      ultrasonic enhancement of doxorubicin growth inhibition in these human bladder
      carcinoma cells was observed. This suggests that either ultrasound does not
      increase doxorubicin uptake by the cell or that doxorubicin uptake is increased
      but in insufficient amounts to affect growth inhibition. Further investigation
      should focus on explaining these results.

PMID- 17173947
TI  - The spatial coding of the inhibition evoked by distractors.
AB  - It is generally agreed that saccade deviations away from a distractor location
      represent inhibition in the oculomotor system. By systematically manipulating the
      location of a distractor we tested whether the inhibition of the distractor is
      coded coarsely or fine-grained. Results showed that the location of a distractor
      had an effect on the saccade trajectories, suggesting that the amount of
      inhibition observed depends on the location of the distractor. More specifically,
      the vertical distance of the distractor from fixation seems to be a determining
      factor. These findings have important implications for models that account for
      inhibition in the target selection process and the areas that could underlie
      inhibitory influences on the superior colliculus (SC), like the frontal eye
      fields (FEF) and the dorsolateral prefrontal cortex (dlPFC). Finally, the initial
      direction and the endpoint of a saccade were found to be strongly correlated,
      which contradicts recent models proposing that the initial saccade direction and
      saccade endpoint are unrelated.

PMID- 17173948
TI  - Dividing attention in the flash-lag illusion.
AB  - A dual-task paradigm was used to examine the effect of withdrawing attentional
      and/or cognitive resources from the flash-lag judgment. The flash-lag illusion
      was larger, and performance in a detection task was generally poorer, under dual
      task conditions than in single-task control conditions. These effects were
      particularly pronounced when decisions in the two tasks were required
      simultaneously, as compared to when they could be made sequentially. The results
      suggest that a time-consuming process is involved in the flash-lag decision, of
      such a nature that prolonging the process increases the magnitude of the
      illusion.

PMID- 17173949
TI  - The role of luminance contrast in the detection of global structure in static and
      dynamic, same- and opposite-polarity, Glass patterns.
AB  - Perception of global structure conveyed in static Glass patterns is difficult,
      though not impossible, when the constituent dipoles are formed by partnering
      opposite polarity dots. We investigate whether the addition of motion signals to
      opposite-polarity Glass patterns can act to restore the perception of global
      structure. The stimuli were concentric Glass patterns consisting of 200 dipoles
      concentrically orientated, or oriented at random orientations, placed on a grey
      background. For each dipole, one luminance-increment dot (Weber contrast of 1)
      was paired with another dot set to a contrast ranging between luminance increment
      and luminance decrement (i.e., a Weber contrast range of approximately -1 to 1).
      Dipoles were either stationary (Experiment 1), or randomly re-positioned at 17Hz
      (Experiment 2), on each frame transition. A two-interval forced-choice paradigm,
      in conjunction with an adaptive staircase, was used to obtain Glass-pattern
      detection thresholds. The task required observers to identify the interval that
      contained concentric Glass structure; the other interval contained randomly
      orientated dipoles. Generally, lower global form thresholds were observed for
      dynamic and same-polarity Glass patterns than for static and opposite-polarity
      Glass patterns. In particular, for dynamic presentations improvement in
      sensitivity was more evident for opposite-polarity than for same-polarity Glass
      patterns. These findings suggest that motion plays an important role in the
      detection of global structure in dynamic Glass patterns.

PMID- 17173950
TI  - Aqueous chlorination of the antibacterial agent trimethoprim: reaction kinetics
      and pathways.
AB  - Trimethoprim (TMP), one of the antibacterials most frequently detected in
      municipal wastewaters and surface waters, reacts readily with free available
      chlorine (i.e., HOCl) at pH values between 3 and 9 (e.g., the pH-dependent
      apparent second-order rate constant, k''(app)=5.6 x 10(1)M(-1)s(-1), at pH 7).
      Solution pH significantly affects the rate of TMP reaction with HOCl. The
      reaction kinetics in reagent water systems can be well described by a second
      order kinetic model incorporating speciation of both reactants and accounting for
      acid-mediated halogenation of TMP's 3,4,5-trimethoxybenzyl moiety. Studies with
      the substructure model compounds 2,4-diamino-5-methylpyrimidine and 3,4,5
      trimethoxytoluene show that TMP reacts with HOCl primarily via its 3,4,5
      trimethoxybenzyl moiety at acidic pH, and with its 2,4-diaminopyrimidinyl moiety
      at circumneutral and alkaline pH. LC/MS product analyses indicate that the TMP
      structure is not substantially degraded upon reactions with HOCl. Instead, a wide
      variety of (multi)chlorinated and hydroxylated products are formed. Experiments
      with real drinking water and wastewater matrixes confirmed that substantial TMP
      transformation can be expected for conditions typical of wastewater and drinking
      water chlorination.

PMID- 17173951
TI  - Simultaneous removal of As, Cd, Cr, Cu, Ni and Zn from stormwater: experimental
      comparison of 11 different sorbents.
AB  - The potential of using alumina, activated bauxsol-coated sand (ABCS), bark,
      bauxsol-coated sand (BCS), fly ash (FA), granulated activated carbon (GAC),
      granulated ferric hydroxide (GFH), iron oxide-coated sand (IOCS), natural zeolite
      (NZ), sand, and spinel (MgAl(2)O(4)) as sorbents for removing heavy metals from
      stormwater are investigated in the present study. The ability of the sorbents to
      remove a mixture of As, Cd, Cr, Cu, Ni and Zn from synthetic stormwater samples
      were evaluated in batch tests at a starting pH of 6.5. The metal speciation and
      saturation data is obtained using the PHREEQ-C geochemical model and used to
      elucidate the sorption data. It is found that BCS, FA, and spinel have
      significantly higher affinity towards heavy metals mainly present as cationic or
      non-charged species (i.e. Cd, Cu, Ni and Zn) compared to those present as anionic
      species (i.e. As and Cr). However, IOCS, NZ and sand have higher affinity towards
      As and Cr, while alumina has equally high affinity to all tested heavy metals.
      The Freundlich isotherm model is found to fit the data in many cases, but ill
      fitted results are also observed, especially for FA, BCS and GAC, possibly due to
      leaching of some metals from the sorbents (i.e. for FA) and oversaturated
      conditions making precipitation the dominant removal mechanism over sorption in
      batches with high heavy metal concentrations and pH. Calculated sorption
      constants (i.e. K(d)) are used to compare the overall heavy metal removal
      efficiency of the sorbents, which in a decreasing order are found to be: alumina,
      BCS, GFH, FA, GAC, spinel, ABCS, IOCS, NZ, bark, and sand. These findings are
      significant for future development of secondary filters for removal of dissolved
      heavy metals from stormwater runoff under realistic competitive conditions in
      terms of initial heavy metal concentrations, pH and ionic strength.

PMID- 17173952
TI  - Biodegradation of poly(propylene glycol)s under the conditions of the OECD
      screening test.
AB  - Two poly(propylene glycol)s (PPGs): PPG 425 and PPG 725 were tested under the
      conditions of the OECD Screening Test with activated sludge as inoculum. Tested
      PPG were the sole source of organic carbon in the test. Quantitative
      determination of the biodegradation progress was performed by the HPLC with
      fluorescence detection after derivatisation of PPG with naphthyl isocyanate. The
      liquid chromatography-mass spectrometry technique was used for identification and
      semiquantitative determination of metabolites. Separation of PPG and metabolites
      from the water matrix was performed by liquid-liquid extraction with chloroform.
      It was found that the shorter PPG 425 is biodegraded significantly worse than the
      longer PPG 725 and that biodegradation occurs without shortening of the PPG chain
      for both PPG. PPG molecules are oxidised to ketones and/or aldehydes during the
      aerobic biodegradation process.

PMID- 17173953
TI  - Susceptibility constants of Escherichia coli and Bacillus subtilis to silver and
      copper nanoparticles.
AB  - Nanoparticle susceptibility constants were defined and used to evaluate the
      antimicrobial characteristics of silver and copper nanoparticles against
      Escherichia coli and Bacillus subtilis. Reaction of copper nanoparticles of 100
      nm with B. subtilis showed the highest susceptibility (Z=0.0734 mL/microg)
      whereas the reaction of silver nanoparticles of 40 nm with E. coli showed the
      lowest one (Z=0.0236 mL/microg).

PMID- 17173954
TI  - Modeling and prediction of photolysis half-lives of polycyclic aromatic
      hydrocarbons in aerosols by quantum chemical descriptors.
AB  - Quantitative structure-property relationship (QSPR) modeling is a powerful
      approach for predicting environmental fate parameters of organic pollutants with
      their structure descriptors. This study reports QSPR models for photolysis half
      lives of polycyclic aromatic hydrocarbons (PAHs) in aerosols. Quantum chemical
      descriptors computed with density functional theory at B3LYP/6-31G(d) level and
      partial least squares (PLS) analysis with optimizing procedure were used for
      generating QSPR models. The correlation coefficient of the optimal model was
      0.993, and the fitting results showed this optimal model had high fitting
      precision and good predictability. The predicted photolysis half-lives by the
      optimal model are very close to those observed. The PLS assistant analysis
      indicated that PAHs with large electronic spatial extent tend to be photolyzed
      faster, while PAHs with high molecular total energy and small Mulliken atomic
      charges on the most negative carbon atom tend to be photolyzed slower in
      aerosols.

PMID- 17173955
TI  - Attenuation of mining-derived pollutants in the hyporheic zone: a review.
AB  - Mine water pollution is a major cause of surface- and groundwater pollution in
      former mining districts throughout Europe. It is a potential barrier to achieving
      good status water bodies, which is a requirement of the EU Water Framework
      Directive. In the UK, a concerted effort has been made over the last decade or so
      to address the scientific and practical challenges relating to the remediation of
      mine water pollution. However, most of this work has focused on remediation of
      point sources of pollution (typically arising from abandoned mines and shafts),
      while the behaviour of mine water at the groundwater-surface water interface (the
      "hyporheic zone") has received far less attention in relevant scientific and
      engineering literature. The extent of mine water pollution and capacity for its
      attenuation at the hyporheic zone has not been well quantified while,
      furthermore, the complex chemical and microbial processes occurring there
      (specifically with reference to mining-derived pollutants) have not been
      investigated in any depth. The absence of such data may relate, in a large part,
      to the difficulty in physically measuring volumes and concentrations associated
      with these river inputs/exports. A far greater body of literature addresses
      biogeochemical processes at the hyporheic zone (especially relating to
      manganese), albeit many such articles relate to aqueous metal dynamics in
      general, rather than mine water specifically. This paper presents a review of the
      natural attenuation processes that may limit the movement and availability of
      mining-derived pollutants at the groundwater-surface water (GW-SW) interface, and
      specifically within the hyporheic zone. A substantial part focuses on
      precipitation and adsorption processes at the hyporheic zone, as well as
      discussing the role of microbial processes in governing metal ion mobility.

PMID- 17173956
TI  - Gene tracking in a family of novel identical twins affected by severe type-III
      von Willebrand Disease (vWD).

PMID- 17173957
TI  - Hyperthermic intraperitoneal chemotherapy in conjunction with surgery for the
      treatment of recurrent ovarian carcinoma.
AB  - OBJECTIVES: To review experience of secondary surgical cytoreduction (SSC) with
      hyperthermic intraperitoneal chemotherapy (IPHC). METHODS: Eligible patients with
      ovarian cancer in whom pre-operative evaluation indicated that there was a good
      possibility that disease could be resected to < or = 5 mm underwent surgery
      followed by intraperitoneal perfusion of cisplatin (100 mg/m2) or mitomycin C (30
      40 mg total dose) heated to 41-43 degrees C (105.8-109.4 degrees F) for 90 min.
      Data for analysis were extracted from retrospective chart review. RESULTS:
      Eighteen patients underwent surgery and IPHC between 9/02 and 3/05.
      Characteristics were median age 64 (37-77) years, mean prior laparotomies 1.4 (0
      3), mean chemotherapy regimens 3.2 (0-7), mean time from initial therapy to IPHC
      30.6 (1-88) months. Original histology: papillary serous 12, poorly
      differentiated adenocarcinoma 1, serous low malignant potential 2, mucinous 1 and
      mixed subtypes 2. 13 had recurrent disease and 5 had persistent disease following
      front-line therapy. 15 received cisplatin and 3 mitomycin C. The mean duration of
      surgery was 9.8 (5-16) h. The maximum dimension of residual lesions at the end of
      surgery prior to IPHC was nil (n=11), < or = 2 mm (n=4), < or = 5 mm (n=2) and <
      or = 10 mm (n=1). Mean time to return of bowel function was 7 (5-20) days and
      mean time to hospital discharge 11.5 (5-49) days. All patients developed CTEP
      grade 1 or 2 metabolic or hematologic toxicities. CTEP grade 3 or 4 metabolic
      toxicity occurred in 72% and a hematologic toxicity in 28%. There was one peri
      operative death due to pulmonary embolus. Median progression-free interval was 10
      months and median overall survival was 31 months. Improved outcome was
      significantly related to the size of residual disease prior to IPHC and
      postoperative chemotherapy. CONCLUSIONS: IPHC is a relatively well-tolerated
      procedure with the majority of the morbidity being related to associated surgery.
      When combined with SSC it has the potential to extend quality life in some
      patients with recurrent ovarian cancer and warrants continued research.
      Randomized studies are needed earlier in the course of the disease.

PMID- 17173958
TI  - Treatment of ovarian cancer with a novel dual targeted conditionally replicative
      adenovirus (CRAd).
AB  - OBJECTIVES: Current virotherapy strategies for ovarian cancer have been hampered
      by limitations in target cell infectivity and nonspecific tissue replication. In
      an effort to circumvent these limitations, we evaluated various CRAds modified to
      incorporate novel capsid targeting motifs (RGD and chimeric Ad5/3) with a novel
      tissue-specific promoter (CXCR4). METHODS: Two novel CRAds (Ad5-CXCR4-F5/3 and
      Ad5-CXCR4-RGD) were constructed via homologous recombination and verified by PCR
      and DNA sequencing. The infectivity and viral replication rates of these two
      CRAds were analyzed via quantitative real-time PCR (QRT-PCR) in cell line
      experiments using three ovarian cancer cell lines (SKOV3.ip1, Hey, and OV4) and
      compared to that achieved with a clinical grade CRAd (delta24-RGD) to be
      evaluated in a Phase I trial. Cytocidal effects were determined by crystal violet
      staining in these same cell lines infected with different concentrations of viral
      particles per cell (0, 0.1, 1, 10, 100, and 500). Additionally, viral replication
      was evaluated by QRT-PCR in primary ovarian cancer tissue slices from multiple
      patients with ovarian cancer as well as in primary human normal liver tissue
      slices in order to establish CRAd selectivity. All experiments incorporated
      appropriate controls and repeated in triplicate. RESULTS: Compared to RGD-capsid
      CRAds (delta24-RGD and CXCR4-RGD), the F5/3-capsid CRAd (CXCR4-F5/3) demonstrated
      significant improvements in infection rates (p=0.025, 0.006, and 0.006) in all
      ovarian cancer cell lines tested (SKOV3.ip1, Hey, and OV4, respectively). In
      addition to improved transduction of virus into the cells, the TSP CXCR4-based
      CRAds demonstrated improved viral replication. Specifically, CXCR4-F5/3 further
      enhanced viral replication 89-fold (p=0.009, 0.010, 0.003) in the same cancer
      cell lines. Furthermore, CXCR4-F5/3 showed a 4-log improvement in oncolytic
      potential over delta24-RGD. In the ex vivo primary ovarian tissue slices, CXCR4
      F5/3 showed a 58-fold improvement in viral replication (p=0.005) compared to the
      clinical grade delta24-RGD. Both CXCR4-F5/3 and CXCR4-RGD demonstrated
      significant reduction of viral replication in normal liver slices (p=0.001).
      CONCLUSIONS: These data suggest that a dual targeted approach is feasible for the
      combined enhancement of infectivity and replication in ovarian cancer with a
      specificity that was attenuated in normal liver tissues. In fact, CXCR4-F5/3
      outperformed our best CRAd agent to date nearly 60-fold in our most stringent ex
      vivo model of primary ovarian cancer tissue slices and suggests that this novel
      agent could be useful for the treatment of ovarian cancer.

PMID- 17173959
TI  - Effective cervical neoplasia detection with a novel optical detection system: a
      randomized trial.
AB  - OBJECTIVE: To assess whether the use of a novel optical detection system (ODS) as
      an adjunct to colposcopy increases the detection of biopsy-confirmed CIN 2,3.
      METHODS: This is a multicenter two-arm randomized trial comparing colposcopy
      alone with colposcopy plus a pre-commercial ODS system that utilizes
      fluorescence, white light tissue reflectance, and cervical video imaging.
      Patients were recruited from 13 colposcopy clinics in a variety of practice
      settings. 2299 women referred for the evaluation of an abnormal cervical cytology
      were randomized with stratification by cytology; subsequently 113 women were
      excluded for a variety of reasons. The main study outcomes were differences in
      true-positive rates (CIN 2,3 and cancer identified) and false-positive rates
      between the study arms. RESULTS: The true-positive (TP) rates were 14.4% vs.
      11.4% (p=0.035, one-sided) for the combined colposcopy and ODS arm compared to
      colposcopy-only arm, respectively, in women with either an atypical squamous cell
      (ASC) or low-grade squamous intraepithelial lesion (LSIL) cytology result. TP
      rates were similar between the two arms among women referred for the evaluation
      of HSIL. The 26.5% gain in true-positives observed with the use of ODS and
      colposcopy among women referred for an ASC or LSIL cytology was achieved with
      only a fractional increase in number of biopsies obtained per patient (0.30) and
      a modest increase in false-positive rate (4%). In the combined colposcopy and ODS
      arm among women with ASC or LSIL, the PPV of biopsies indicated by ODS was 15.0%
      and the PPV of biopsies indicated by colposcopy was 15.2%. Joint hypothesis
      testing indicates that ODS and colposcopy provides benefit compared to colposcopy
      alone among women with ASC or LSIL. CONCLUSIONS: Combining ODS with colposcopy
      provides a clinically meaningful increase in the detection of CIN 2,3 in women
      referred for the evaluation of mildly abnormal cytology results.

PMID- 17173960
TI  - Radical vaginal trachelectomy and laparoscopic pelvic lymphadenectomy for early
      stage cervical cancer in patients who desire to preserve fertility.

PMID- 17173962
TI  - Anticonflict effects of lavender oil and identification of its active
      constituents.
AB  - The pharmacological effects of lavender oil were investigated using two conflict
      tests in ICR mice, and then the active constituents were identified. Lavender oil
      produced significant anticonflict effects at 800 and 1600 mg/kg in the Geller
      conflict test and at 800 mg/kg in the Vogel conflict test, suggesting that the
      oil has an anti-anxiety effect. Analysis using GC/MS revealed that lavender oil
      contains 26 constituents, among which alpha-pinene (ratio, 0.22%), camphene
      (0.06%), beta-myrcene (5.33%), p-cymene (0.3%), limonene (1.06%), cineol (0.51%),
      linalool (26.12%), borneol (1.21%), terpinene-4-ol (4.64%), linalyl acetate
      (26.32%), geranyl acetate (2.14%) and caryophyllene (7.55%) were identified. We
      examined the effects of linalool, linalyl acetate, borneol, camphene, cineol,
      terpinen-4-ol, alpha-pinene and beta-myrcene using the Geller and Vogel conflict
      tests in ICR mice. Cineol, terpinen-4-ol, alpha-pinene and beta-myrcene did not
      produce any significant anticonflict effects in the Geller test. Linalyl acetate
      did not produce any significant anticonflict effects in either test. Both borneol
      and camphene at 800 mg/kg produced significant anticonflict effects in the
      Geller, but not in the Vogel conflict test. Linalool, a major constituent of
      lavender oil, produced significant anticonflict effects at 600 and 400 mg/kg in
      the Geller and Vogel tests, respectively, findings that were similar to those of
      lavender oil. Thus, we concluded that linalool is the major pharmacologically
      active constituent involved in the anti-anxiety effect of lavender oil.

PMID- 17173961
TI  - Withdrawal from chronic nicotine in adolescent and adult rats.
AB  - The purpose of the present experiment is to assess potential differences in
      nicotine withdrawal in both adolescent and adult rats. Nicotine dependence was
      induced via osmotic minipump in adolescent rats (releasing 22.2 mg/kg/day on
      Postnatal Day 28) and adults (release rate of 18.4 mg/kg/day on Postnatal Day
      60); differential initial release rates were used across age to compensate for
      the more rapid weight gain of adolescents. On Day 7 of nicotine exposure,
      withdrawal was induced via the administration of a nicotinic antagonist,
      mecamylamine (1.0 mg/kg i.p.), and withdrawal-induced anxiogenesis assessed on
      the elevated plus maze. On Days 1 and 4 after pump removal, animals were examined
      for startle responses and prepulse inhibition in an acoustic startle chamber.
      Adult animals exhibited a nicotine withdrawal-induced increase in anxiety, while
      adolescents did not. One day following the removal of minipumps, only nicotine
      dependent adolescent animals exhibited a disruption in prepulse inhibition.
      Nicotine withdrawal failed to produce an alteration in acoustic startle response
      in either group. Together these data suggest that ontogenic differences in
      nicotine withdrawal are dependent on the withdrawal measure examined, with
      adolescents being less sensitive than adults to anxiety-like symptoms, while
      being more sensitive to withdrawal-induced cognitive disruption.

PMID- 17173963
TI  - Prevalence of cigarette and bidi smoking among rickshaw pullers in Dhaka city.
AB  - OBJECTIVE: Rickshaw pullers in Dhaka city, Bangladesh are exposed to severe air
      pollution due to their long stay on city roads. In addition, smoking could
      further jeopardize their health status. The objective of this study is to
      estimate the prevalence of cigarette and bidi smoking among the rickshaw pullers
      in Dhaka city. METHODS: One thousand rickshaw pullers (100 from each of the 10
      blocs of Dhaka city) were randomly chosen and underwent interviewer administered
      questionnaire survey during August-October 2003. Data on demographics, education,
      rickshaw-pulling, smoking status, duration, and daily consumption were collected
      by 4 trained interviewers using pre-tested questionnaire. Prevalence of cigarette
      and bidi smoking, and their sociodemographic correlates were examined using
      bivariate and multivariate analyses. RESULTS: The overall prevalence of current
      smoking was 75.9%, while the prevalence of cigarette, bidi and both smoking were
      39.2%, 15.7% and 20.9%, respectively. Multinomial logistic regression analysis
      showed that those who were older, had lower mean schooling years and smoked more
      sticks per day are more likely to be bidi or both smokers. CONCLUSION: The
      prevalence of smoking among rickshaw pullers is very high compared to that in
      general population. Immediate intervention programs are warranted to reduce the
      future burden of smoking related morbidity among them who are already exposed to
      tremendous pollution on city roads.

PMID- 17173964
TI  - The representation of discourse in the two hemispheres: an individual differences
      investigation.
AB  - Two experiments were conducted to investigate discourse representation in the two
      cerebral hemispheres as a function of reading skill. We used a lateralized visual
      field procedure to compare left hemisphere (LH) and right hemisphere (RH)
      sensitivity to different discourse relations in readers with varying skill
      levels. In Experiment 1, we investigated two levels of discourse representation
      in memory: (a) the propositional representation and (b) the discourse model. We
      found that all readers were sensitive to propositional relations in the LH. In
      contrast, sensitivity to propositional relations in the RH increased as a
      function of reading skill. In addition, reading skill was positively related to
      topic relations in the LH, whereas it was negatively in the RH. In Experiment 2,
      we investigated propositional relations of different distances and again found
      that all readers were sensitive to propositional relations in the LH, whereas
      sensitivity to propositional relations in the RH was negatively related to
      reading skill. In general, reading skill appears to be associated with left
      lateralized discourse representations.

PMID- 17173965
TI  - Individuation and parents as people: measurement concerns regarding two aspects
      of autonomy.
AB  - The focus of this study was on examining two assumed components of adolescent
      autonomy-individuation and perceiving parents as people and the validity of their
      measurement. Participating in the study were 67 students in grades 9 and 11 (ages
      14-17 years) and 118 college students (ages 18-27 years). Each student completed
      two measures of individuation and two measures of parents as people. The sample
      was divided into four data sets for analyses based on gender and age grouping.
      Neither the two measures of individuation nor the two measures of parents as
      people correlated with each other indicating a problem with concurrent validity.
      The problems with adequate grounding in theory and validity for the measures are
      discussed.

PMID- 17173967
TI  - Structure and properties of regenerated Antheraea pernyi silk fibroin in aqueous
      solution.
AB  - Antheraea pernyi silk fibroin fibers were dissolved by aqueous lithium
      thiocyanate to obtain regenerated A. pernyi silk fibroin solution. By means of
      circular dichroism, (13)C NMR and Raman spectroscopy, the molecular conformation
      of regenerated A. pernyi silk fibroin in aqueous solution was investigated. The
      relationship of environmental factors and sol-gel transformation behavior of
      regenerated A. pernyi silk fibroin was also studied. The molecular conformations
      of regenerated A. pernyi silk fibroin mainly were alpha-helix and random coil in
      solution. There also existed a little beta-sheet conformation. It was obviously
      different with Bombyx mori silk fibroin, whose molecular conformation in solution
      was only random coil but no alpha-helix existence. With the increase of
      temperature and solution concentration and with the decrease of solution pH
      value, the gelation velocity of regenerated A. pernyi silk fibroin solution
      increased. Especially, it showed that A. pernyi silk fibroin was more sensitive
      to temperature than B. mori silk fibroin during the sol-gel transformation. The
      velocity increased obviously when the temperature was above 30 degrees C. During
      the sol-gel transformation, the molecular conformation of regenerated A. pernyi
      silk fibroin changed from random coil to beta-sheet structure. The results of
      these studies provided important insight into the preparation of new biomaterials
      by silk fibroin protein.

PMID- 17173966
TI  - The protective effects of osmolytes on arginine kinase unfolding and aggregation.
AB  - Osmolytes are a series of different kinds of small molecules that can maintain
      the correct conformation of protein by acting as molecular chaperons. In this
      study, the protective effects of four compatible osmolytes, i.e., proline,
      sucrose, DMSO and glycerol, were studied during arginine kinase (EC 2.7.3.3)
      unfolding and aggregation. The results showed that all the osmolytes applied in
      this study obviously prevented AK unfolding and inactivation that was due to a
      GdnHCl denaturant by reducing the inactivation rate constants (k(i)), increasing
      the transition free energy changes (DeltaDeltaG(i)) and increasing the value for
      the midpoint of denaturation (C(m)). Furthermore, the osmolytes remarkably
      prevented AK aggregation in a concentration-dependent manner during AK refolding.
      Our results strongly indicated that osmolytes were not only metabolism
      substrates, but they were also important compounds with significant physiological
      protective functions for proteins, especially in some extremely harsh
      environments.

PMID- 17173968
TI  - Molecular requirements for L-type Ca2+ channel blockade by testosterone.
AB  - Despite being generally perceived as detrimental to the cardiovascular system,
      testosterone has marked beneficial vascular effects; most notably it acutely and
      directly causes vasodilatation. Indeed, men with hypotestosteronaemia can present
      with myocardial ischemia and angina which can be rapidly alleviated by infusion
      of testosterone. To date, however, in vitro studies have failed to provide a
      convincing mechanism to account for this clinically important effect. Here, using
      whole-cell patch-clamp recordings to measure current flow through recombinant
      human L-type Ca2+ channel alpha(1C) subunits (Ca(v)1.2), we demonstrate that
      testosterone inhibits such currents in a concentration-dependent manner.
      Importantly, this occurs over the physiological range of testosterone
      concentrations (IC50 34 nM), and is not mimicked by the metabolite 5alpha
      androstan-17beta-ol-3-one (DHT), nor by progesterone or estradiol, even at high
      (10 microM) concentration. L-type Ca2+ channels in the vasculature are also
      important clinical targets for vasodilatory dihydropyridines. A single point
      mutation (T1007Y) almost completely abolishes nifedipine sensitivity in our
      recombinant expression system. Crucially, the same mutation renders the channels
      insensitive to testosterone. Our data strongly suggest, for the first time, the
      molecular requirements for testosterone binding to L-type Ca2+ channels, thereby
      supporting its beneficial role as an endogenous Ca2+ channel antagonist in the
      treatment of cardiovascular disease.

PMID- 17173969
TI  - Targeting the Na(+)/H(+) exchanger: an old concept with new perspectives in the
      treatment of hematological malignancies.

PMID- 17173970
TI  - The determination of earthworm species sensitivity differences to cadmium
      genotoxicity using the comet assay.
AB  - The concept of species sensitivity differences is important in ecotoxicology and
      environmental risk assessment, but testing usually focuses on lethality of
      toxicants. The effects on the suborganismal level are mostly ignored; therefore,
      the present study assessed a biomarker of genotoxicity (the alkaline comet assay)
      to compare species sensitivities. Five earthworm species (Amynthas diffringens,
      Aporrectodea caliginosa, Dendrodrilus rubidus, Eisenia fetida and Microchaetus
      benhami) were exposed for 48 h to sublethal concentrations of cadmium sulphate in
      reconstituted soil water and DNA integrity was evaluated with the parameter Tail
      DNA %. Significant amounts of DNA damage were detected in three (A. caliginosa,
      D. rubidus and E. fetida) species. E. fetida exhibited the highest level of DNA
      damage, although D. rubidus showed the highest increase (3-fold) in DNA damage
      from the control. All exposed earthworms accumulated Cd, although body loads did
      not correspond with DNA damage levels; most of the Cd was probably sequestrated
      and rendered harmless.

PMID- 17173971
TI  - Oleandrin induces apoptosis in human, but not in murine cells: dephosphorylation
      of Akt, expression of FasL, and alteration of membrane fluidity.
AB  - Common practice to evaluate the efficacy of any compound as drug is done in cell
      based in vitro system followed by in vivo murine model prior to clinical trial in
      human. Cardiac glycosides are very effective to kill human cells, but not murine
      cells. In this report, we describe the comparative molecular mechanism of
      oleandrin, a cardiac glycoside action in human and murine cells. Treatment with
      oleandrin facilitated nuclear translocation of FKHR in human, but not murine
      cells by dephosphorylating Akt. It activated MAPK and JNK in human, but not in
      murine cells and also induced expression of FasL leads to apoptosis in human
      cells as detected by assaying caspases activation, PARP cleavage, nuclear
      fragmentation, and annexin staining. Oleandrin interacted with human plasma
      membrane as evaluated by HPLC, altered its fluidity as detected by DPH binding,
      inhibited Na+/K+-ATPase activity, and increased intracellular free Ca2+ level
      followed by calcineurin activity only in human, but not in murine cells. Results
      suggest that human plasma membrane might be different than murine, which interact
      with oleandrin that disturb Na+/K+-ATPase pump resulting in the calcification
      followed by induction of Ca2+-dependent cellular responses such as apoptosis.

PMID- 17173973
TI  - TLR2 and TLR4 agonists synergistically up-regulate SR-A in RAW264.7 through p38.
AB  - It is known that macrophage scavenger receptor A (SR-A) can protect mice from
      endotoxemia. In addition, Escherichia coli O111:B4 LPS from Sigma (sLPS), which
      contains both TLR4 and TLR2 agonists, was previously reported to be able to
      induce SR-A expression on murine macrophage cell line RAW264.7. However, the
      relative role of both TLR4 and TLR2 agonists from Sigma (sLPS) in the up
      regulation of SR-A on RAW264.7 is still undefined. Here, we found that sLPS could
      only slightly up-regulate SR-A on RAW264.7 following removing its TLR4 and TLR2
      agonists, respectively. In contrast, the combination of TLR4 agonist uLPS (re
      extracted sLPS) and TLR2 agonist Pam3CSK4 dramatically induced SR-A expression,
      and synergistically promoted RAW264.7 to bind and internalize FITC-LPS
      specifically through SR-A. The combination had no such effect either on TLR2 or
      TLR4 expression, and incubation with IL-6, IL-10, IL-12 or TNF-alpha alone could
      not induce SR-A expression on RAW264.7. In addition, treatment with a NF-kappaB
      inhibitor pyrrolidine dithiocarbamate (PDTC) could only weakly suppress the up
      regulation of SR-A by the combination. However, the combination synergistically
      promoted MAPK p38 phosphorylation, and p38 specific inhibitor SB203580 completely
      suppressed its inducible effect on SR-A expression. Hence, we demonstrated that
      up-regulation of SR-A by sLPS was resulted from the cooperation of its TLR4 and
      TLR2 agonists through p38, and we also presented a novel synergy effect of TLR2
      and TLR4 agonists.

PMID- 17173972
TI  - Classical pathway complement activation on human endothelial cells.
AB  - Endothelial cells regulate vascular integrity and express complement binding
      proteins including gC1qR/p33 (gC1qR), which recognize C1q, a subunit of the first
      component of the classical complement pathway. Experiments were performed to
      investigate classical complement pathway activation on resting endothelial cells
      and endothelial cells exposed to shear stress. C1q deposition and C4 activation
      (C4d) were demonstrated by solid phase ELISA and flow cytometry on human
      microvascular and umbilical vein endothelial cells after exposure to serum or
      plasma. C4d deposition was accompanied by downstream complement activation
      including C3b and C5b-9 deposition. C4 activation failed to occur in C1q depleted
      serum, but was not affected by Factor B depleted serum, confirming classical
      complement pathway activation. Moreover, C4 activation occurred following
      exposure of endothelial cells to purified C1 and C4, in the absence of other
      plasma proteins, and in the absence of detectable cell surface IgG and IgM. Shear
      stress (18 dynes/cm2) increased C1q (n=9, p<0.05) and C4d (n=9, p<0.05)
      deposition approximately two-fold, and enhanced endothelial cell gC1qR expression
      (n=7, p<0.05). Treatment of endothelial cells with anti gC1qR monoclonal antibody
      F(ab')2 fragments reduced C4d deposition by approximately 20% (n=5, p<0.05).
      These data demonstrate direct classical complement pathway activation on
      endothelial cells. gC1qR appears to play a minor but definable role, whereas cell
      surface IgG or IgM are not required.

PMID- 17173974
TI  - Alcohol consumption and risk of cataract extraction: a prospective cohort study
      of women.
AB  - PURPOSE: To investigate the association between alcohol consumption and the risk
      of cataract extraction. DESIGN: Population-based prospective cohort study.
      PARTICIPANTS: A total of 34,713 women participating in the Swedish Mammography
      Cohort, age 49 to 83 years, completed in 1997 a self-administered questionnaire
      about alcohol, smoking, and other lifestyle factors. METHODS: The women were
      followed from September 1997 through September 2004. The cohort was matched with
      registers of cataract extraction from the study area. MAIN OUTCOME MEASURES:
      Incident surgical extraction of age-related cataract. RESULTS: During 84 months
      of follow-up, we found 3587 incident cases of age-related cataract extraction.
      Compared with never drinkers, the relative risk of cataract extraction among
      current drinkers was 1.11 (95% confidence interval [CI] 1.02-1.21) after
      adjustment for age and other potential risk factors. In multivariate analysis, an
      increment of 13 g alcohol intake per day (corresponding to 1 drink = 330 ml of
      beer, 150 ml of wine, or 45 ml of liquor) was associated with a 7% increased risk
      of cataract extraction (relative risk, 1.07; 95% CI 1.02-1.12). Mean age at
      cataract extraction among nonsmoking women who used alcohol was 75 years,
      compared with 77.6 years among never drinkers. CONCLUSIONS: These prospective
      data suggest that daily use of >/=1 alcoholic drinks was associated with a modest
      increase of risk for cataract extraction. The risk increased with increasing
      alcohol consumption.

PMID- 17173975
TI  - Effects of N-alkyl and ammonium groups on the hydrolytic cleavage of DNA with a
      Cu(II)TACH (1,3,5-triaminocyclohexane) complex. Speciation, kinetic, and DNA
      binding studies for reaction mechanism.
AB  - cis,cis-1,3,5-Triaminocyclohexane (c-TACH), its N-alkyl-derivatives (alkyl =
      methyl, ethyl), and trans,cis-1,3,5-triaminocyclohexane (t-TACH) were prepared,
      and speciation and DNA cleaving property of Cu(II) complexes of these ligands
      were investigated. All of the complexes efficiently promote the hydrolytic
      cleavage of supercoiled plasmid DNA under physiological conditions without
      further additives. The DNA cleavage rate (V(obs)) trend at pH values between 8
      and 9 is N-Me(3) = N-Et(1) < t-TACH < c-TACH < N-Et(2) < N-Et(3). At pH 7, the
      trend is c-TACH < N-Et(3) = N-Et(2) < N-Et(1) < N-Me(3) << t-TACH. The cleavage
      rate constants at 35 degrees C, for the c-TACH complex are 3 x 10(-1) h(-1) at pH
      8.1 and 2 x 10(-1) h(-1) at pH 7.0 ([DNA] = 7 microM, [Cu(II)-complex] = 105
      microM). The hydrolytically active species at pH > 8 is CuL(H(2)O)(OH)(+) in
      which L coordinates to Cu(II) as a tridentate ligand for all complexes except for
      t-TACH. The hydrolytically active species at pH 7 is CuLH(H(2)O)(3)(3+) or
      CuLH(H(2)O)(4)(3+) in which LH coordinates as bidentate ligand. DNA-binding
      constants of c-TACH and t-TACH complexes are presented and the effects of N-alkyl
      and ammonium groups are discussed in light of the proposed reaction mechanism.

PMID- 17173976
TI  - Phosphene induction by microstimulation of macaque V1.
AB  - Non-human primates are being used to develop a cortical visual prosthesis for the
      blind. We use the properties of electrical microstimulation of striate cortex
      (area V1) of macaque monkeys to make inferences about phosphene induction. Our
      analysis is based on well-established properties of V1: retino-cortical
      magnification factor, receptive-field size, and the characteristics of
      hypercolumns. We argue that phosphene size is dependent on the amount of current
      delivered to V1 and on the retino-cortical magnification factor. We suggest that
      to improve the correspondence between the site of stimulation within V1 and the
      visual field location of an elicited phosphene both eyes must be put under
      experimental control given that phosphene location is retinocentric and given
      that the vergence angle between the eyes might affect the position of a phosphene
      in depth. Knowing how electrical microstimulation interacts with cortical tissue
      to evoke percepts in behaving macaque monkeys is fundamental to the establishment
      of an effective cortical visual prosthesis for the blind.

PMID- 17173978
TI  - Decreased plasma BDNF level in depressive patients.
AB  - BACKGROUND: Recent reports have suggested a pathophysiological role for brain
      derived neurotrophic factor (BDNF) in major depressive disorder (MDD). We
      evaluated plasma levels of BDNF in patients with MDD. METHODS: Plasma BDNF levels
      were measured in 77 MDD patients and 95 normal controls. The severity of
      psychiatric symptoms was measured with the Hamilton Depression Rating Scale and
      the Brief Psychiatric Rating Scale. RESULTS: Plasma BDNF levels were
      significantly lower in MDD patients than in normal control subjects (p<0.001).
      Plasma BDNF levels were significantly lower in MDD patients with recurrent
      episodes than in MDD patients with the first episode or normal controls
      (p<0.001). Plasma BDNF levels were significantly lower in non-psychotic MDD
      patients than in psychotic MDD patients or normal controls (p<0.001). Plasma BDNF
      in suicidal MDD patients were significantly lower than those in non-suicidal MDD
      patients (p<0.001). LIMITATIONS: We measured only plasma levels of BDNF. However,
      the cellular sources of BDNF in human plasma are not yet clearly defined.
      CONCLUSIONS: Our study suggests that there is a decrease in plasma BDNF levels in
      untreated MDD patients. However, relapsed or recurrent episodes, suicidal
      behavior, and psychotic features could also affect the plasma levels of BDNF.
      Further studies are required to understand the source and role of the circulating
      BDNF in depression.

PMID- 17173977
TI  - Systematic review of the effect of psychological interventions on family
      caregivers of people with dementia.
AB  - BACKGROUND: Caregivers of people with dementia are at high risk of psychological
      morbidity and associated breakdown in care. Many psychologically based
      interventions have been designed to help caregivers of people with dementia. More
      work is needed to identify which, if any, are helpful for such caregivers.
      METHOD: We conducted a systematic review of the immediate and long term efficacy
      of different types of psychological interventions for the psychological health of
      caregivers of people with dementia, using standardized criteria, to assist
      clinicians in implementing rational, evidence-based management recommendations.
      We reviewed studies examining the effects of any therapy derived from a
      psychological approach that satisfied pre-specified criteria. Using the Oxford
      Centre for Evidence-Based Medicine criteria we rated the quality of each study,
      extracted data and gave overall ratings to different types of intervention.
      RESULTS: We identified 244 references in our search of which 62 met our inclusion
      criteria. LIMITATIONS: Our findings are limited by lack of good quality evidence,
      with only ten level 1 studies identified. CONCLUSIONS: We found excellent
      evidence for the efficacy of six or more sessions of individual behavioral
      management therapy centered on the care recipient's behavior in alleviating
      caregiver symptoms both immediately and for up to 32 months. Teaching caregivers
      coping strategies either individually or in a group also appeared effective in
      improving caregiver psychological health both immediately and for some months
      afterwards. Group interventions were less effective than individual
      interventions. Education about dementia by itself, group behavioral therapy and
      supportive therapy were not effective caregiver interventions.

PMID- 17173979
TI  - Adhesion molecule expression in the bovine mammary gland.
AB  - The bovine mammary gland requires lymphocytes for immune protection of the gland
      from foreign pathogens and, in addition, to transfer immune protection to the
      neonate via colostrum and milk. The process of homing primed lymphocytes to
      tissues is mediated by the interaction of cell-adhesion molecules displayed on
      the surface of lymphocytes and counter receptors displayed on the vascular
      endothelium. This study was conducted to identify the cell-adhesion molecules
      involved in homing lymphocytes to the bovine mammary gland at four different
      physiological stages; pregnant, colostral, lactation and involution. The
      expression and distribution of adhesion molecules in alveolar tissues and
      supramammary lymph nodes from the mammary glands of healthy cows was determined
      in situ by immunohistochemical analysis and compared with bovine Peyer's patch,
      used as a typical mucosal-associated lymphoid tissue and positive control. The
      mucosal addressin molecule, MAdCAM-1, was not detected in bovine mammary tissues
      at any of the four different physiological stages. Absence of MAdCAM-1 expression
      was verified by quantitative real-time RT-PCR analysis. Transcription levels of
      MAdCAM-1 mRNA were found to be more then 5 x 10(3)-fold lower in mammary alveolar
      tissues compared with bovine Peyer's patch tissues. In contrast to MAdCAM-1,
      phase-dependent protein expression of VCAM-1 was detected in both mammary
      alveolar tissues and the supramammary lymph nodes, with the highest expression
      observed in colostral phase cows. The protein expression in mammary alveolar
      tissues was limited to larger venules, although in colostral phase cows, VCAM-1
      was also detected around the alveoli perimeter. In the supramammary lymph node,
      VCAM-1 protein was observed on both small and large venules. PNAd was detected in
      supramammary lymph nodes at all physiological stages of the mammary gland;
      however, it was not found in mammary alveolar tissues. Lymphocytes expressing
      beta7 were not detected in mammary tissues and lymphocytes expressing CD62L were
      only observed in the supramammary lymph nodes. Overall the data suggest that
      MAdCAM-1 and VCAM-1 are not involved in homing lymphocytes to the bovine mammary
      gland; whereas, VCAM-1 and PNAd may have this role in the supramammary lymph
      node.

PMID- 17173980
TI  - Participation of iNOS-derived NO in hypothalamic activation and vasopressin
      release during polymicrobial sepsis.
AB  - Clinical and experimental studies with LPS injection have shown an increase in
      vasopressin (AVP) secretion in the early phase of severe sepsis, which is
      subsequently reduced despite persistent hypotension. The aim of this study was to
      evaluate the role of inducible nitric oxide synthase (iNOS)-derived NO in
      hypothalamic activation and in AVP release during severe sepsis induced by cecal
      ligation and puncture (CLP). Male Wistar rats received i.p. injections of
      aminoguanidine, an iNOS inhibitor, or saline 30 min before CLP or sham surgeries
      (controls). CLP led to increased plasma nitrate levels, protein leakage and
      hypotension and caused mortality of 80% by 24 h. Expression of c-fos in
      paraventricular (PVN), supraoptic (SON) and organum vasculosum of lamina
      terminalis (OVLT) nuclei, as well as plasma AVP concentration were increased at 6
      h but reduced to basal levels 24 h after CLP. Aminoguanidine pre-treatment
      prevented the increase in plasma nitrate levels and hypotension in the first 6 h.
      It also reduced AVP secretion and hypothalamic c-fos expression. After 24 h, the
      pre-treatment reduced plasma nitrate levels, protein leakage and caused a partial
      recovery of c-fos expression in SON and OVLT but did not affect AVP release.
      Furthermore, mortality was reduced to 43%. We conclude that during the early
      phase of severe sepsis hypotension caused by the iNOS-derived NO is partially
      responsible for the hypothalamic activation and AVP release. In the late phase,
      however, the iNOS-derived NO prevents brain activation blunting AVP secretion
      contributing to hypotension, irreversible shock and animal death.

PMID- 17173981
TI  - Space, time and dopamine.
AB  - In recent years, dopamine has emerged as a key neurotransmitter that is crucially
      involved in incentive motivation and reinforcement learning. Dopamine release is
      evoked by rewards. The extensive divergence of outputs from a small number of
      dopaminergic neurons suggests a spatially nonselective action of dopamine, but it
      reinforces the specific actions that led to reward. How is this achieved? We
      propose that the selectivity of dopamine effects is achieved by the timing of
      dopamine release in relation to the activity of glutamatergic synapses, rather
      than by spatial localization of the dopamine signal to specific synaptic
      contacts. The synaptic mechanisms of these actions are unknown but reduced levels
      of dopamine, for example in Parkinson's disease, leads to a paucity of
      behavioural output, whereas its excess production has been associated with
      psychiatric problems. Clearly, there are therapeutic imperatives that require a
      better understanding of how dopamine functions at a synaptic level.

PMID- 17173982
TI  - Simultaneously inhibition of HIV and HBV replication through a dual small
      interfering RNA expression system.
AB  - Human immunodeficiency virus (HIV) is often acquired in individuals already
      infected with hepatitis B virus (HBV) as a result of shared routes of
      transmission. Since current options for the treatment of HIV and HBV infections
      are limited, there is an essential need for the development of effective
      therapies against HIV/HBV co-infections. RNA interference (RNAi) has been used as
      a powerful tool to silence genes in cells and animals. In this study, we
      developed a small interfering RNA generation system that expressed two different
      siRNAs to target the HBs gene of HBV and the gp120 gene of HIV in Bel-7402 and
      HEK293T cells, respectively. Our results demonstrated that the two siRNA
      molecules could simultaneously inhibit the expression of HBs and gp120 by 81% and
      89%, respectively. In addition, dual siRNA molecules significantly decreased the
      production of HBs, and simultaneously inhibited the replication of HBV and HIV.
      This dual siRNA generation system not only proved to be a novel approach for
      studying functions of multiple genes simultaneously, but also provides a
      potential approach for the treatment and prevention of HIV and HBV co-infection.

PMID- 17173983
TI  - On the role of the reticular formation in vocal pattern generation.
AB  - This review is an attempt to localize the brain region responsible for pattern
      generation of species-specific vocalizations. A catalogue is set up, listing the
      criteria considered to be essential for a vocal pattern generator. According to
      this catalogue, a vocal pattern generator should show vocalization-correlated
      activity, starting before vocal onset and reflecting specific acoustic features
      of the vocalization. Artificial activation by electrical or glutamatergic
      stimulation should produce artificially sounding vocalization. Lesioning is
      expected to have an inhibitory or deteriorating effect on vocalization.
      Anatomically, a vocal pattern generator can be assumed to have direct or, at
      least, oligosynaptic connections with all the motoneuron pools involved in
      phonation. A survey of the literature reveals that the only area meeting all
      these criteria is a region, reaching from the parvocellular pontine reticular
      formation just above the superior olive through the lateral reticular formation
      around the facial nucleus and nucleus ambiguus down to the caudalmost medulla,
      including the dorsal and ventral reticular nuclei and nucleus retroambiguus. It
      is proposed that vocal pattern generation takes place within this whole region.

PMID- 17173984
TI  - Rat 22kHz ultrasonic vocalizations as alarm cries.
AB  - Rats incorporate circa 22kHz ultrasonic alarm cries into their defense pattern in
      response to a predator threat. These calls are dependent on conspecific presence,
      show gender differences, and tend to be emitted from a place of relative safety.
      Rats emit sonic defensive threat vocalizations when approached by a potential
      threat. These are emitted regardless of conspecific presence, and increase as a
      function of threat proximity, eventually culminating in defensive attack at close
      distances. Ample data from field studies suggest a similar division of
      vocalizations into alarm or warning cries, and defensive threat vocalizations,
      although both are often subsumed under the rubric of "alarm cries". A clear
      distinction between these types of calls is necessary for proper analysis of the
      evolutionary mechanisms responsible for the development and maintenance of each
      of them. Furthermore, the integration of data from field studies and laboratory
      experiments may prove useful in evaluation of the relationship between each type
      of cry and emotional (fear or anxiety-like) states in mammals.

PMID- 17173985
TI  - Abnormalities in skilled reaching movements are improved by peripheral
      anesthetization of the less-affected forelimb after sensorimotor cortical
      infarcts in rats.
AB  - Unilateral damage to sensorimotor cortical (SMC) regions can profoundly impair
      skilled reaching function in the contralesional forelimb. Such damage also
      results in impairments and compensatory changes in the less-affected/ipsilesional
      forelimb, but these effects remain poorly understood. Furthermore,
      anesthetization of the ipsilesional hand in humans with cerebral infarcts has
      been reported to produce transient functional improvements in the paretic hand
      [Floel A, Nagorsen U, Werhahn KJ, Ravindran S, Birbaumer N, Knecht S, et al.
      Influence of somatosensory input on motor function in patients with chronic
      stroke. Ann Neurol 2004;56:206-12; Voller B, Floel A, Werhahn KJ, Ravindran S, Wu
      CW, Cohen LG. Contralateral hand anesthesia transiently improves poststroke
      sensory deficits. Ann Neurol 2006;59:385-8]. One aim of this study was to
      sensitively assay the bilateral effects of unilateral ischemic SMC damage on
      performance of a unimanual skilled reaching task (the single pellet retrieval
      task) that rats had acquired pre-operatively with each forelimb. The second aim
      was to determine whether partially recovered contralesional reaching function is
      influenced by anesthetization of the ipsilesional forelimb. Unilateral SMC
      lesions were found to result in transient ipsilesional impairments in reaching
      success and significant ipsilesional abnormalities in reaching movements compared
      with sham-operates. There were major contralesional reaching impairments which
      improved during a 4 week training period, but movements remained significantly
      abnormal. Anesthetization of the ipsilesional forelimb with lidocaine at this
      time attenuated the contralesional movement abnormalities. These findings
      indicate that unilateral ischemic SMC lesions impair skilled reaching behavior in
      both forelimbs. Furthermore, after partial recovery in the contralesional
      forelimb, additional improvements can be induced by transient anesthetization of
      the ipsilesional forelimb. This is consistent with the effects of unilateral
      anesthetization in humans which have been attributed to the modulation of
      competitive interhemispheric interactions. The present findings suggest that such
      interactions are also likely to influence skilled reaching function in rats.

PMID- 17173987
TI  - Kinetic characterization of inosine monophosphate dehydrogenase of Leishmania
      donovani.
AB  - Trypanosomatid protozoan pathogens are purine auxotrophs that are highly
      dependent on the enzyme inosine monophosphate dehydrogenase (IMPDH) for the
      synthesis of guanylate nucleotides. Enzymatic characterization of the Leishmania
      donovani IMPDH (LdIMPDH) overexpressed in E. coli revealed that this enzyme was
      highly specific for the substrates IMP and NAD(+) with K(m)(app) values of 33 and
      390 microM, respectively. In contrast to other IMPDHs, LdIMPDH exhibits no
      substrate inhibition in high concentrations of NAD(+). Kinetic studies revealed
      that XMP and GMP were inhibitors with K(i) values of approximately 26 and 210
      microM, respectively, suggesting that these nucleotides may regulate LdIMPDH
      activity. Mycophenolic acid was also a potent inhibitor of L. donovani IMPDH with
      a K(i) value of approximately 25 nM. Confocal immunofluorescence microscopy and
      subcellular fractionation localized LdIMPDH to the glycosome. Protein-protein
      interaction assays revealed that LdIMPDH associated tightly with glycosomal
      protein sorting receptor LdPEX5.

PMID- 17173986
TI  - Dynamic multipathway modeling of Cd bioaccumulation in Daphnia magna using
      waterborne and dietborne exposures.
AB  - We tested the predictive ability of the dynamic multipathway bioaccumulation
      model (DYMBAM) to characterize Cd accumulation in Daphnia magna, a species
      commonly used in toxicity tests and because of its sensitivity, particularly to
      metals, a species that is relied upon in ecological risk assessments. We
      conducted chronic exposure experiments in which D. magna were exposed to either
      dietborne Cd alone or to both dietborne and waterborne Cd. In the food-only
      treatments, the algae Chlamydomonas reinhardtii or Pseudokirchneriella
      subcapitata were pre-exposed to free Cd ion concentrations, [Cd(2+)], from 0.001
      to 100nM (0.001-11microgL(-1)) then, on a daily feeding renewal basis, fed to D.
      magna over 21 days. In the water plus food treatment, D. magna were exposed for
      21 days to the same range of [Cd(2+)] and fed with the same algal species that
      had been exposed to Cd at various concentrations. In the algal exposure media, Cd
      concentrations in algae were directly related to those in water and were
      characterized by a linear regression model using the log transformed
      concentration of the WHAM predicted Cd(2+) concentration. The DYMBAM was used
      with estimated values of the model constants for ingestion rate (0.08-0.34gg(
      1)day(-1)) and growth rate (0.085-0.131day(-1)) based on our experimental data
      and with literature values for rate constants of Cd influx and efflux as well as
      Cd assimilation efficiency. Measured Cd concentrations in D. magna agreed with
      model predictions within a factor of 3. Using the model, we predict that food is
      an important contributor of Cd burden to D. magna, particularly at lower Cd
      exposure concentrations over an environmentally realistic gradient of free Cd in
      water. However, this cladoceran also takes up Cd from water and this exposure
      route becomes increasingly important at very high concentrations of free Cd
      (>10nM or 1.1microgL(-1)). Nevertheless, Cd produced lethal effects in D. magna
      that were exposed to this metal in water and diet, but exposure to Cd in food
      only did not result in toxic effects (as measured by survival and reproduction).

PMID- 17173988
TI  - Coronary artery anatomy in children with congenital heart disease by computed
      tomography.
AB  - AIMS: To evaluate electron beam computed tomography (EBCT) for recognition of
      coronary artery patterns in children with congenital heart diseases. METHODS:
      Institutional review board approval was obtained; informed consents were not
      required. A total of 226 children diagnosed with Tetralogy of Fallot (n=122),
      double outlet right ventricle (n=52), transposition of the great arteries (n=34),
      and congenitally corrected transposition (n=18) who had undergone cardiac EBCT at
      our institution between 1995 and 2002 were identified. Iodinated contrast medium
      was injected with arterial phase acquisition. The two radiologists and one
      pediatric cardiologist that interpreted the EBCT images and cardiac angiograms,
      respectively, were blinded to each other's results. Surgical and cardiac
      angiogram findings were compared to the EBCT results. Descriptive statistics were
      used to compare efficacy. RESULTS: Numerous aberrant patterns were clearly
      identified on the EBCT images. Pattern IX occurred in most patients with
      Tetralogy of Fallot or double outlet right ventricle. Patterns I and 0 are the
      most common coronary artery types in transposition of the great arteries and
      congenitally corrected transposition, respectively. Overall diagnostic accuracy
      for all disease groups was 82.7%. The diagnostic accuracy of the coronary
      arterial anatomy by EBCT increased with older age, and was more than 90% in
      individuals aged over 3 months. CONCLUSION: EBCT is effective for identification
      of the coronary anatomy of children with specific congenital heart diseases,
      except for neonates and small infants less than 3 months of age.

PMID- 17173989
TI  - Phage cocktail to control the exponential growth of normal flora in processed
      sputum specimens grown overnight in liquid medium for rapid TB diagnosis.
AB  - The mechanical pressure exerted during centrifugation and the chemical pressure
      experienced when sputum specimens are processed, leave the tubercle bacilli in
      the sputum unsuitable for rapid detection especially in phage based assays. Thus,
      growing Mycobacterium tuberculosis in broth, at least overnight, is mandatory for
      allowing the tubercle bacilli to recoup. During this time the surviving
      colonizing flora grow faster and overgrow tubercle bacilli interfering with TB
      diagnosis. In the present study normal flora surviving the action of 4% NaOH was
      isolated and characterized. Phages capable of killing 14 different species
      representing this normal flora were isolated from soil and sewage samples and
      characterized. A novel and bio-friendly approach to treat sputum samples with a
      cocktail of three phages capable of killing most of the 14 representative
      organisms and not infecting mycobacteria is explored to control the overgrowth of
      colonizing bacteria in broth culture. While 26 of the 100 sputum samples
      processed by modified Petroff's procedure showed growth of colonizing flora on
      blood agar, all of them when grown in broth overnight showed mixed, confluent
      growth. The addition of phagebiotics controlled them all, showing a significant
      reduction in colony forming units but resulting in few discrete colonies in 54
      samples. Isolation of phages capable of controlling these surviving organisms and
      including them in the phagebiotics mixture should lead to the control of
      colonizing bacteria effectively.

PMID- 17173990
TI  - Universal external RNA controls for microbial gene expression analysis using
      microarray and qRT-PCR.
AB  - Gene expression analysis provides significant insight to understand regulatory
      mechanisms of biology, yet acquisition and reproduction of quality data, as well
      as data confirmation and verification remain challenging due to a lack of proper
      quality controls across different assay platforms. We present a set of six
      universal external RNA quality controls for microbial mRNA expression analysis
      that can be applied to both DNA oligo microarray and real-time qRT-PCR including
      using SYBR Green and TaqMan probe-based chemistry. This set of controls was
      applied for Saccharomyces cerevisiae and Pseudomonas fluorescens Pf-5 microarray
      assays and qRT-PCR for yeast gene expression analysis. Highly fitted linear
      relationships between detected signal intensity and mRNA input were described.
      Valid mRNA detection range, from 10 to 7000 pg and from 100 fg to 1000 pg were
      defined for microarray and qRT-PCR assay, respectively. Quantitative estimation
      of mRNA abundance was tested using randomly selected yeast ORF including function
      unknown genes using the same source of samples by the two assay platforms.
      Estimates of mRNA abundance by the two methods were similar and highly correlated
      in an overlapping detection range from 10 to 1000 pg. The universal external RNA
      controls provide a means to compare microbial gene expression data derived from
      different experiments and different platforms for verification and confirmation.
      Such quality controls ensure reliability and reproducibility of gene expression
      data, and provide unbiased normalization reference for validation,
      quantification, and estimate of variation of gene expression experiments.
      Application of these controls also improves efficiency and facilitates high
      throughput applications of gene expression analysis using the qRT-PCR assay.

PMID- 17173991
TI  - A simple nucleic acid hybridization/latex agglutination assay for the rapid
      detection of polymerase chain reaction amplicons.
AB  - We have developed a new method for the detection of nucleic acid hybridization,
      based on a simple latex agglutination test that can be evaluated by the unaided
      eye. Nucleic acid, e.g., a polymerase chain reaction (PCR) product, is denatured
      and incubated with polystyrene beads carrying covalently bound complementary
      oligonucleotide sequences. Hybridization of the nucleic acids leads to
      aggregation of the latex particles, thereby verifying the presence of target
      sequence. The test is performed at room temperature, and results are available
      within 10 min. As a proof of principle, the hybridization/latex agglutination
      assay was applied to the detection of purified PCR fragments either specific for
      Salmonella spp. or a synthetic sequence, and to the detection of Salmonella
      enterica in artificially contaminated chicken samples. A few nanograms of
      purified PCR fragments were detectable. In artificially contaminated chicken
      samples, 3 colony-forming units (cfu)/25 g were detected in one of three
      replicates, and 30 cfu/25 g were detected in both of two replicates when samples
      for PCR were taken directly from primary enrichment, demonstrating the practical
      applicability of this test system. Even multiplex detection might be achievable.
      This novel kind of assay could be useful for a range of applications where
      hybridization of nucleic acids, e.g., PCR fragments, is to be detected.

PMID- 17173992
TI  - Aquatic zooremediation: deploying animals to remediate contaminated aquatic
      environments.
AB  - The ability of animals to act in a bioremediative capacity is not widely known.
      Animals are rarely considered for bioremediation initiatives owing to ethical or
      human health concerns. Nonetheless, specific examples in the literature reveal
      that some animal species are effective remediators of heavy metals, microbial
      contaminants, hydrocarbons, nutrients and persistent organic pollutants,
      particularly in an aquatic environment. Recent examples include deploying pearl
      oysters to remove metals and nutrients from aquatic ecosystems and the harvest of
      fish to remove polychlorinated biphenyls (PCBs) from the Baltic. It is probable
      that many animal taxa will possess attributes amenable to bioremediation. We
      introduce zoological equivalents of the definitions used in phytoremediation
      literature (zooextraction, zootransformation, zoostabilization and animal
      hyperaccumulation), to serve as useful benchmarks in the evaluation of candidate
      animal species for zooremediation initiatives, and propose that recognition of
      the concept of zooremediation would act to stimulate discussion and future
      research in this area.

PMID- 17173993
TI  - Biotech's defining moments.
AB  - Confusion about terms related to biotechnology--genetic modification, GMOs,
      genetic engineering, transgenic, and all the rest--has been around for decades.
      This definitional dysfunction has created myriad opportunities for mischief and
      given rise to widespread over-regulation, diminished agricultural R&D, ill
      advised conferences and risk assessment studies, flawed analyses (including a
      recent tome from the OECD), fear-mongering by NGOs, and a perplexed public.
      Greater precision in terminology would improve the lot of scientists, the quality
      of public policy and, eventually, human and environmental health.

PMID- 17173994
TI  - Immobilisation of proteins by atomic clusters on surfaces.
AB  - In this Opinion article, we describe a nanotechnology-based approach to
      immobilize and orient proteins onto surfaces using atomic clusters prepared by
      physical methods. This is relevant to future protein biochips where dilute arrays
      of protein binding sites, each designed to immobilize no more than one protein
      molecule, would be ideal. In the case of a surface consisting of size-selected
      atomic gold clusters, proteins containing free cysteine residues can chemisorb
      directly to the bare cluster surface, thus effecting oriented immobilisation. The
      selection of atomic gold clusters in the size range 1-100 atoms (<3nm in
      diameter) is intended to ensure that, typically, only one protein can bind
      directly to the cluster surface. These nanoclusters of a smaller size scale than
      that of the protein present minimal contact between the gold and the protein, and
      hence imply a reduced risk of protein denaturing compared with gold films or
      extended surfaces.

PMID- 17173995
TI  - Finger flexor motor control patterns during active flexion: an in vivo tendon
      force study.
AB  - An in vivo tendon force measurement system was used to evaluate index finger
      flexor motor control patterns during active finger flexion. During open carpal
      tunnel release surgery (N=12) the flexor digitorum profundus (FDP) and flexor
      digitorum superficilias (FDS) tendons were instrumented with buckle force
      transducers and participants performed finger flexion at two different wrist
      angles (0 degrees or 30 degrees ). During finger flexion, there was concurrent
      change of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joint
      angles, but the FDP and FDS tendon force changes were not concurrent. For the FDS
      tendon, no consistent changes in force were observed across participants at
      either wrist angle. For the FDP tendon, there were two force patterns. With the
      wrist in a neutral posture, the movement was initiated without force from the
      finger flexors, and further flexion (after the first 0.5s) was carried out with
      force from the FDP. With the wrist in a flexed posture, the motion was generally
      both initiated and continued using FDP force. At some wrist postures, finger
      flexion was initiated by passive forces which were replaced by FDP force to
      complete the motion.

PMID- 17173996
TI  - Overexpression of human CD38/ADP-ribosyl cyclase enhances acetylcholine-induced
      Ca2+ signalling in rodent NG108-15 neuroblastoma cells.
AB  - The role of cyclic ADP-ribose (cADPR) and its synthetic enzyme, CD38, as a
      downstream signal of muscarinic acetylcholine receptors (mAChRs) was examined in
      neuroblastoma cells expressing M1 mAChRs (NGM1). NGM1 cells were further
      transformed with both wild-type and mutant (C119K/C201E) human CD38. The dual
      transformed cells exhibited higher cADPR formation than ADPR production and
      elevated intracellular free Ca(2+) concentrations ([Ca(2+)](i)) in response to
      ACh. These phenotypes were analyzed in detail in a representative CD38 clone. The
      intracellular cADPR concentration by ACh application was significantly increased
      by CD38 overexpression. Digital image analysis by a confocal microscopy revealed
      that topographical distribution of the sites of Ca(2+) release was unchanged
      between control and overexpressed cells. These results indicate that cADPR is an
      intracellular messenger of Ca(2+) signalling, suggesting that CD38 can contribute
      to mAChR-cADPR signalling.

PMID- 17173997
TI  - Sensitive Listeria spp. immunoassay based on europium(III) nanoparticulate labels
      using time-resolved fluorescence.
AB  - Listeria spp. are Gram-positive rod shaped bacteria found universally in the
      environment. Pathogenic Listeria monocytogenes is seldom harmful to healthy
      adults, but can cause serious disease, listeriosis, especially to pregnant women,
      neonates, and elderly or immunocompromised people. Conventional methods for
      screening Listeria in food samples are time consuming and laborious, involving
      the use of a range of liquid media and plate cultures. In the current study, the
      total analysis time was shortened by employing a sensitive Listeria assay, which
      was able to detect the bacteria in low concentrations. Sensitivity of the
      sandwich immunoassay was substantially improved by utilizing europium(III)
      chelate containing latex nanoparticles as tracers. Each 107 nm nanoparticle
      contained approximately 31000 europium(III)-chelates which enhanced the specific
      activity of the label. The sensitive nanoparticulate immunoassay developed for
      Listeria spp. was performed in one-step and two-step formats. One-step assay was
      notably faster, 15 min, and simpler to execute having analytical sensitivity of
      300 CFU/ml and a dynamic range of three orders of magnitude. The sensitivity, 20
      CFU/ml, of the 4 h two-step assay clearly exceeded that of the one-step assay,
      and the dynamic range was nearly five orders of magnitude. Food and environmental
      samples were measured against a commercial L. monocytogenes immunoassay with good
      correlation. The developed sensitive assay enabled shorter sample enrichment
      times and, therefore, faster analysis of Listeria spp. Obviously the detection of
      several other bacteria can also be enhanced by applying the nanoparticle assay
      technology.

PMID- 17173998
TI  - Characterization of integrons and tetracycline resistance determinants in
      Aeromonas spp. isolated from South African aquaculture systems.
AB  - An increasing incidence of multidrug resistance amongst Aeromonas spp. isolates,
      which are both fish pathogens and emerging opportunistic human pathogens, has
      been observed worldwide. This can be attributed to the horizontal transfer of
      mobile genetic elements, viz.: plasmids and class 1 integrons. The antimicrobial
      susceptibilities of 37 Aeromonas spp. isolates, from tilapia, trout and koi
      aquaculture systems, were determined by disc-diffusion testing. The plasmid
      content of each isolate was examined using the alkaline lysis protocol. Tet
      determinant type was determined by amplification using two degenerate primer sets
      and subsequent HaeIII restriction. The presence of integrons was determined by
      PCR amplification of three integrase genes, as well as gene cassettes, and the
      qacEDelta1-sulI region. Thirty-seven Aeromonas spp. isolates were differentiated
      into six species by aroA PCR-RFLP, i.e., A. veronii biovar sobria, A. hydrophila,
      A. encheleia, A. ichtiosoma, A. salmonicida, and A. media. High levels of
      resistance to tetracycline (78.3%), amoxicillin (89.2%), and augmentin (86.5%)
      were observed. Decreased susceptibility to erythromycin was observed for 67.6% of
      isolates. Although 45.9% of isolates displayed nalidixic acid resistance,
      majority of isolates were susceptible to the fluoroquinolones. The MAR index
      ranged from 0.12 to 0.59, with majority of isolates indicating high-risk
      contamination originating from humans or animals where antibiotics are often
      used. Plasmids were detected in 21 isolates, with 14 of the isolates displaying
      multiple plasmid profiles. Single and multiple class A family Tet determinants
      were observed in 27% and 48.7% of isolates, respectively, with Tet A being the
      most prevalent Tet determinant type. Class 1 integron and related structures were
      amplified and carried different combinations of the antibiotic resistance gene
      cassettes ant(3'')Ia, aac(6')Ia, dhfr1, oxa2a and/or pse1. Class 2 integrons were
      also amplified, but the associated resistance cassettes could not be identified.
      Integrons and Tet determinants were carried by 68.4% of isolates bearing
      plasmids, although it was not a strict association. These plasmids could
      potentially mobilize the integrons and Tet determinants, thus transferring
      antimicrobial resistance to other water-borne bacteria or possible human
      pathogens. The identification of a diversity of resistance genes in the absence
      of antibiotic selective pressure in Aeromonas spp. from aquaculture systems
      highlights the risk of these bacteria serving as a reservoir of resistance genes,
      which may be transferred to other bacteria in the aquaculture environment.

PMID- 17173999
TI  - The effects of growth temperature and growth phase on the inactivation of
      Listeria monocytogenes in whole milk subject to high pressure processing.
AB  - The aim of this study was to explore the effect of a wide range of growth
      temperatures, growth phases and plating media on the inactivation of Listeria
      monocytogenes by high pressure processing (HPP). In part one, L. monocytogenes
      was grown to mid-stationary phase at 4, 15, 25, 35 or 43 degrees C, inoculated
      into whole UHT milk at approximately 10(7) CFU/ml and high pressure processed at
      400 MPa at room temperature (20-25 degrees C). Afterward, the HPP milk was plated
      on Tryptic Soy Yeast Extract Agar (TSYEA) and Modified Oxford Agar (MOX) to
      determine the degree of injury. For part two, cells were grown to mid
      exponential, late-exponential or mid-stationary phase at 15 or 43 degrees C and
      processed in the same way. Time to reach a 5-log reduction was determined and
      data were analysed by ANOVA. The results from part one showed that both growth
      temperature and plating medium had a significant effect (P < 0.001) on the
      inactivation of stationary phase L. monocytogenes by HPP. Tukey's pairwise
      comparisons revealed that the effects of all temperatures, except 35 and 43
      degrees C, were significantly different (P < 0.05). Cells grown at 15 degrees C
      were most sensitive to HPP, followed by cells grown at 4, 25 or 35 degrees C,
      with cells grown at 43 degrees C appearing to be the most resistant. Inactivation
      of cells grown at 4, 15 or 25 degrees C followed first order kinetics, whereas
      cells grown at 35 or 43 degrees C displayed non-linear inactivation kinetics due
      to tailing. In part two, both growth phase and plating medium had significant
      effects on the inactivation (P < or = 0.001) of L. monocytogenes by HPP. Cells
      grown at 15 degrees C to mid-stationary phase were the most pressure-resistant
      when tested on both media, and were significantly more resistant (P < 0.05) than
      cells grown at the same temperature to the other two phases of growth. There was
      no significant difference between mid- and late-exponential phase cells grown at
      15 degrees C. When cells were grown at 43 degrees C, mid-exponential phase cells
      were significantly more sensitive (P < 0.05) than either late-exponential or mid
      stationary phase cells, with no difference between late-exponential or mid
      stationary phase cells. It was postulated that membrane composition, stationary
      phase proteins and/or stress proteins may affect pressure resistance.

PMID- 17174000
TI  - Evaluation of Chenopodium ambrosioides oil as a potential source of antifungal,
      antiaflatoxigenic and antioxidant activity.
AB  - Essential oil extracted from the leaves of Chenopodium ambrosioides Linn.
      (Chenopodiaceae) was tested against the aflatoxigenic strain of test fungus
      Aspergillus flavus Link. The oil completely inhibited the mycelial growth at 100
      microg/ml. The oil exhibited broad fungitoxic spectrum against Aspergillus niger,
      Aspergillus fumigatus, Botryodiplodia theobromae, Fusarium oxysporum, Sclerotium
      rolfsii, Macrophomina phaseolina, Cladosporium cladosporioides, Helminthosporium
      oryzae and Pythium debaryanum at 100 microg/ml. The oil showed significant
      efficacy in inhibiting the aflatoxin B1 production by the aflatoxigenic strain of
      A. flavus. During in vivo investigation it protected stored wheat from different
      storage fungi for one year. Chenopodium oil also exhibited potent antioxidant
      activity when tested by ABTS method. All these observations suggest the possible
      exploitation of the Chenopodium oil as potential botanical fungitoxicant in
      ecofriendly control of post harvest biodeterioration of food commodities from
      storage fungi.

PMID- 17174001
TI  - Efficacy of recA gene sequence analysis in the identification and discrimination
      of Lactobacillus hilgardii strains isolated from stuck wine fermentations.
AB  - Conventional phenotypic methods sometimes lead to misidentification of some
      heterofermentative wine lactobacilli such as Lactobacillus hilgardii,
      Lactobacillus buchneri, and Lactobacillus brevis. We establish the specificity of
      16S rDNA sequencing in the differentiation of these species and in the rejection
      of the Lactobacillus vermiforme species name. Moreover, we succeeded in
      differentiating these heterofermentative species by means of recA gene sequence
      comparison. Short homologous regions were amplified by PCR with degenerate
      consensus primers, sequenced, and 280 bp were analysed and considered for the
      inference of phylogenetic trees. The phylogram obtained was coherent and clearly
      separated the three species. The recA gene sequence was a reliable and useful
      method that allowed a good discrimination among closely related species. The
      validity of the recA gene sequence, restriction fragment length polymorphism
      (RFLP) analysis of the PCR-amplified 16S-23S rDNA intergenic spacer region (ISR),
      and random amplified polymorphic DNA (RAPD) to study the L. hilgardii
      intraspecies heterogeneity was tested in five strains isolated from stuck wine
      fermentations at the same winery in the same vintage. The results indicated that
      L. hilgardii is a heterogeneous species. Since L. hilgardii is a malolactic
      species that can influence the final quality of the wine, the presence of
      oenological relevant genes, such as those involved in ethyl carbamate or biogenic
      amine production, was investigated.

PMID- 17174002
TI  - Micro-colony array based high throughput platform for enzyme library screening.
AB  - Enzymes are becoming increasingly important tools for synthesizing and modifying
      fine and bulk chemicals. The availability of biocatalysts which fulfil the
      requirements of industrial processes is often limited. Recruiting suited enzymes
      from natural (e.g. metagenomes) and artificial (e.g. directed evolution)
      biodiversity is based on screening libraries of microbial clones expressing
      enzyme variants. However, exploring the complex diversity of such libraries needs
      efficient screening methods. Overcoming the "screening bottleneck" requires rapid
      high throughput technology allowing the analysis of a large diversity of
      different enzymes and applying different screening conditions. Facing these facts
      an efficient and cost effective method for high throughput screening of large
      enzyme libraries at the colony level was developed. Therefore, ordered high
      density micro-colony arrays were combined with optical sensor technology and
      automated image analysis. The system generally allows the simultaneous monitoring
      of enzyme activities reflected by up to 7000 micro-colonies spotted on a filter
      in the size of a micro-titer plate. A developed replica option also allows the
      analysis of clones under varying external conditions. The method was verified by
      a model screening using esterases and was proved to provide reliable enzyme
      activity measurements within single micro-colonies allowing the discrimination of
      activity differences in the range of 10-20%.

PMID- 17174003
TI  - Java-based framework for processing and displaying short-echo-time magnetic
      resonance spectroscopy signals.
AB  - Magnetic resonance spectroscopy (MRS) can be used to determine in a non-invasive
      way the concentrations of certain chemical substances, also called metabolites.
      The spectra of MRS signals contain peaks that correspond to the metabolites of
      interest. Short-echo-time signals are characterized by heavily overlapping
      metabolite peaks and require sophisticated processing methods. To be useful in a
      clinical environment tools are needed that can process those signals in an
      accurate and fast way. Therefore, we developed novel processing methods and we
      designed a freely available and open-source framework
      (http://www.esat.kuleuven.ac.be/sista/members/biomed) in which the processing
      methods can be integrated. The framework has a set of abstract classes, called
      hot spots, and its goal is to provide a general structure and determine the
      control flow of the program. It provides building blocks or components in order
      to help developers with integrating their methods in the framework via a plug-in
      system. The framework is designed with the unified modeling language (UML) and
      implemented in Java. When a developer implements the framework he gets an
      application that acts like a simple and user-friendly graphical user interface
      (GUI) for processing MRS data. This article describes in detail the structure and
      implementation of the framework and the integration of our processing methods in
      it.

PMID- 17174004
TI  - Why evolutionary biologists should be demographers.
AB  - Evolution is driven by the propagation of genes, traits and individuals within
      and between populations. This propagation depends on the survival, fertility and
      dispersal of individuals at each age or stage during their life history, as well
      as on population growth and (st)age structure. Demography is therefore central to
      understanding evolution. Recent demographic research provides new perspectives on
      fitness, the spread of mutations within populations and the establishment of life
      histories in a phylogenetic context. New challenges resulting from individual
      heterogeneity, and instances where survival and reproduction are linked across
      generations are being recognized. Evolutionary demography is a field of exciting
      developments through both methodological and empirical advances. Here, we review
      these developments and outline two emergent research questions.

PMID- 17174005
TI  - Inference in ecology and evolution.
AB  - Most ecologists and evolutionary biologists continue to rely heavily on null
      hypothesis significance testing, rather than on recently advocated alternatives,
      for inference. Here, we briefly review null hypothesis significance testing and
      its major alternatives. We identify major objectives of statistical analysis and
      suggest which analytical approaches are appropriate for each. Any well designed
      study can improve our understanding of biological systems, regardless of the
      inferential approach used. Nevertheless, an awareness of available techniques and
      their pitfalls could guide better approaches to data collection and broaden the
      range of questions that can be addressed. Although we should reduce our reliance
      on significance testing, it retains an important role in statistical education
      and is likely to remain fundamental to the falsification of scientific
      hypotheses.

PMID- 17174006
TI  - Storm water runoff concentration matrix for urban areas.
AB  - The infrastructure (roads, sidewalk, commercial and residential structures) added
      during the land development and urbanisation process is designed to collect
      precipitation and convey it out of the watershed, typically in existing surface
      water channels, such as streams and rivers. The quality of surface water, seepage
      water and ground water is influenced by pollutants that collect on impervious
      surfaces and that are carried by urban storm water runoff. Heavy metals, e.g.
      lead (Pb), zinc (Zn), copper (Cu), cadmium (Cd), polycyclic aromatic hydrocarbons
      (PAH), mineral oil hydrocarbons (MOH) and readily soluble salts in runoff,
      contribute to the degradation of water. An intensive literature search on the
      distribution and concentration of the surface-dependent runoff water has been
      compiled. Concentration variations of several pollutants derived from different
      surfaces have been averaged. More than 300 references providing about 1300 data
      for different pollutants culminate in a representative concentration matrix
      consisting of medians and extreme values. This matrix can be applied to long-term
      valuations and numerical modelling of storm water treatment facilities.

PMID- 17174007
TI  - How many infection control staff do we need in hospitals?
AB  - During a one-day workshop experienced infection control practitioners (ICPs) and
      medical microbiologists debated how much time was needed for the delivery of
      infection control activities in a model hospital. They agreed a standard of one
      full-time equivalent (FTE) ICP per 178 hospital beds and one FTE medical
      microbiologist per 806 hospital beds. This is 40% and 24% more than the usual
      standard, respectively. Now that official numbers of hospital beds have become an
      inadequate parameter for work delivered by hospitals, a new standard is proposed,
      with the number of admissions as the denominator. This is one FTE ICP per 5000
      admissions and one medical microbiologist or epidemiologist per 25000 admissions.

PMID- 17174008
TI  - Candida albicans outbreak in a neurosurgical intensive care unit.

PMID- 17174010
TI  - High glucose promotes the release and expression of novel vasoactive peptide,
      coupling factor 6, in human umbilical vein endothelial cells.
AB  - As a novel vasoactive peptide, plasma coupling factor 6 (CF6) was shown to be
      elevated in patients with diabetes mellitus, yet the mechanism involved is
      unknown. We studied CF6 protein release and its potential mechanism in human
      umbilical vein endothelial cells (HUVECs) incubated with high glucose levels.
      High glucose level enhanced CF6 expression and peptide secretion in HUVECs in a
      time- and concentration-dependent manner, which was independent of increased
      osmolarity. PKC or p38 MAPK inhibition significantly suppressed high glucose
      mediated CF6 release in HUVECs, and the inhibition rate was -45% and -30%,
      respectively. Also, high glucose-induced CF6 production was antagonized by
      insulin treatment. Hence, high glucose increases the expression and secretion of
      CF6 in endothelial cells and appears to be mediated by PKC and p38 MAPK activity.

PMID- 17174009
TI  - Expression of genes encoding antimicrobial and bradykinin-related peptides in
      skin of the stream brown frog Rana sakuraii.
AB  - Peptidomic analysis of an extract of the skin of the stream brown frog Rana
      sakuraii Matsui and Matsui, 1990 led to the isolation of a C-terminally alpha
      amidated peptide (VR-23; VIGSILGALASGLPTLISWIKNR x NH2) with broad-spectrum
      antimicrobial activity that shows structural similarity to the bee venom peptide,
      melittin together with two peptides belonging to the temporin family (temporin
      1SKa; FLPVILPVIGKLLNGIL x NH2 and temporin-1SKb; FLPVILPVIGKLLSGIL x NH2), and
      peptides whose primary structures identified them as belonging to the brevinin-2
      (2 peptides) and ranatuerin-2 (1 peptide) families. Using a forward primer that
      was designed from a conserved region of the 5'-untranslated regions of Rana
      temporaria preprotemporins in a 3'-RACE procedure, a cDNA clone encoding
      preprotemporin-1SKa was prepared from R. sakuraii skin total RNA. Further
      preprotemporin cDNAs encoding temporin-1SKc (AVDLAKIANIAN KVLSSL F x NH2) and
      temporin-1SKd (FLPMLAKLLSGFL x NH2) were obtained by RT-PCR. Unexpectedly, the 3'
      RACE procedure using the same primer led to amplification of a cDNA encoding a
      preprobradykinin whose signal peptide region was identical to that of
      preprotemporin-1SKa except for the substitution Ser18-->Asn. R. sakuraii
      bradykinin ([Arg0,Leu1,Thr6,Trp8] BK) was 28-fold less potent than mammalian BK
      in effecting B2 receptor-mediated relaxation of mouse trachea and the des[Arg0]
      derivative was only a weak partial agonist. The evolutionary history of the
      Japanese brown frogs is incompletely understood but a comparison of the primary
      structures of the R. sakuraii dermal peptides with those of Tago's brown frog
      Rana tagoi provides evidence for a close phylogenetic relationship between these
      species.

PMID- 17174011
TI  - Platelet beta-secretase activity is increased in Alzheimer's disease.
AB  - beta-Secretase activity is the rate-limiting step in Abeta peptide production
      from amyloid precursor protein. Abeta is a major component of Alzheimer's disease
      (AD) cortical amyloid plaques. beta-Secretase activity is elevated in post mortem
      brain tissue in AD. The current study investigated whether beta-secretase
      activity was also elevated in peripheral blood platelets. We developed a novel
      fluorimetric beta-secretase activity assay to investigate platelets isolated from
      individuals with AD (n=86), and age-matched controls (n=115). Platelet membrane
      beta-secretase activity (expressed as initial rate) varied over fourfold between
      individuals, raising important questions about in vivo regulation of this
      proteolytic activity. Nonetheless, we identified a significant 17% increase in
      platelet membrane beta-secretase activity in individuals with AD compared to
      controls (p=0.0003, unpaired t-test). Platelet membrane beta-secretase activity
      did not correlate with mini-mental state examination (MMSE) score in the AD group
      (mean MMSE=17.7, range 1-23), indicating that the increase did not occur as a
      secondary result of the disease process, and may even have preceded symptom
      onset.

PMID- 17174014
TI  - An exploratory study identifying the programme related stressors amongst
      qualified nurses completing part-time degree courses.
AB  - The aim of this paper is to explore the leading programmatic stressors and
      associated age related stressors experienced by two cohorts of students (n=132)
      completing part time degree programmes in nursing in two third level institutions
      in the Republic of Ireland. To date the literature has exclusively focused on the
      day to day stressors that undergraduate nursing student's experience. The design
      chosen was descriptive utilising a questionnaire as the mode of data collection.
      'Preparing assignments for submission', 'trying to balance work commitments and
      the required study', 'doing the course assignments', 'the demands of writing an
      assignment to the necessary level', the prospect of the final examination' and
      'preparing for the course examination' were all ranked as the leading stressors.
      The younger participants in this study were more likely to register higher
      degrees of stress as a result of the process stressors of their studies owing to
      the negative correlation with age. Process stressors were associated with the
      academic workload and time management difficulties. The findings have wider
      implications for educationalists in relation to course development and ongoing
      student support. Educationalists need to be cognizant in particular of the age
      related stressors associated with completing part time degree programmes.

PMID- 17174012
TI  - Detection of prodromal Alzheimer's disease via pattern classification of magnetic
      resonance imaging.
AB  - We report evidence that computer-based high-dimensional pattern classification of
      magnetic resonance imaging (MRI) detects patterns of brain structure
      characterizing mild cognitive impairment (MCI), often a prodromal phase of
      Alzheimer's disease (AD). Ninety percent diagnostic accuracy was achieved, using
      cross-validation, for 30 participants in the Baltimore Longitudinal Study of
      Aging. Retrospective evaluation of serial scans obtained during prior years
      revealed gradual increases in structural abnormality for the MCI group, often
      before clinical symptoms, but slower increase for individuals remaining
      cognitively normal. Detecting complex patterns of brain abnormality in very early
      stages of cognitive impairment has pivotal importance for the detection and
      management of AD.

PMID- 17174013
TI  - Selective loss of nigral dopamine neurons induced by overexpression of truncated
      human alpha-synuclein in mice.
AB  - Parkinson's disease is characterized by loss of nigral dopaminergic neurons and
      presence of Lewy bodies, whose major component is alpha-synuclein. In the present
      study, we generated transgenic mice termed Syn130m that express truncated human
      alpha-synuclein (amino acid residue number: 1-130) in dopaminergic neurons.
      Notably, dopaminergic neurons were selectively diminished in the substantia nigra
      pars compacta of Syn130m, while transgenic mice that expressed comparable amount
      of full-length human alpha-synuclein did not develop such pathology. Therefore,
      the truncation of human alpha-synuclein seems to be primarily responsible for the
      loss of nigral dopaminergic neurons. The nigral pathology resulted in impairment
      of axon terminals in the striatum and concomitant decrease in striatal dopamine
      content. Behaviorally, spontaneous locomotor activities of Syn130m were reduced,
      but the abnormality was ameliorated by treatment with L-DOPA. The loss of nigral
      dopaminergic neurons was not progressive and seemed to occur during embryogenesis
      along with the onset of expression of the transgene. Our results indicate that
      truncated human alpha-synuclein is deleterious to the development and/or survival
      of nigral dopaminergic neurons.

PMID- 17174015
TI  - Effect of selenium supplementation on biochemical markers and outcome in
      critically ill patients.
AB  - BACKGROUND & AIMS: This study aimed to assess the effect of high dose selenium
      (Se) supplementation on Se status in blood, oxidative stress, thyroid function
      and possible effects on requirement for renal replacement therapy (RRT) in
      severely septic patients admitted to the intensive care unit (ICU). METHODS: This
      prospective single-centre study was carried out in 40 septic ICU patients who
      were randomized to high dose Se (Se+ group, N=18 (474, 316, 158 microg/day), each
      for 3 consecutive days followed by a standard dose of 31.6 microg/day of Se given
      as sodium selenite whereas the control group (Se-, N=22) received only the
      standard dose of Se. Plasma Se, glutathione peroxidase (GSH-Px), F2 isoprostanes,
      thyroid function tests (total T4 and total T3), C-reactive protein (CRP) and red
      blood cell (RBC) GSH-Px were estimated on day 0, 3, 7, 14. RESULTS: In the Se+
      group, plasma Se increased by day 3 and 7 (P<0.0001) and day 14 (P=0.02), plasma
      GSH-Px increased by day 3 and 7 (P=0.01) as compared to Se- group. There was a
      significant negative correlation between plasma Se and SOFA (sepsis related organ
      failure assessment) (r=-0.36, P=0.03) along with low plasma Se and high CRP at
      the time of admission. Requirement for renal replacement therapy was not
      significantly different between the groups. CONCLUSION: Although high dose Se
      supplementation increased plasma Se and GSH-Px activity, it did not reduce
      oxidative damage or the requirement for RRT. Se levels in blood are influenced by
      redistribution and severity of illness and therefore should be interpreted with
      caution.

PMID- 17174016
TI  - The meaning of patient involvement and participation in health care
      consultations: a taxonomy.
AB  - A number of trends, pressures and policy shifts can be identified that are
      promoting greater patient involvement in health care delivery through
      consultations, treatments and continuing care. However, while the literature is
      growing fast on different methods of involvement, little attention has been given
      so far to the role which patients themselves wish to play, nor even of the
      conceptual meanings behind involvement or participation. This article reviews the
      current models of involvement in health care delivery as derived from studies of
      professional views of current and potential practice, prior to examining the
      empirical evidence from a large-scale qualitative study of the views and
      preferences of citizens, as patients, members of voluntary groups, or neither.
      Individual domiciliary interviews were carried out with 44 people recruited from
      GP practices in northern England. These respondents were then included in a
      second phase of 34 focus groups in 6 different localities in northern and
      southern England, of which 22 were with individuals unaffiliated to any
      voluntary/community groups, 6 related to local voluntary/community groups with
      specific interests in health or health care, and 6 related to groups without such
      specific interests. A final set of 12 workshops with the same samples helped to
      confirm emergent themes. The qualitative data enabled a taxonomy of patient
      desired involvement to be derived, which is contrasted with professional
      determined levels of involvement identified from the literature. Participation is
      seen as being co-determined by patients and professionals, and occurring only
      through the reciprocal relationships of dialogue and shared decision-making. Not
      everyone wanted to be involved and the extent to which involvement was desired
      depended on the contexts of type and seriousness of illness, various personal
      characteristics and patients' relationships with professionals. These levels are
      seen to provide basic building blocks for a more sophisticated understanding of
      involvement within and between these contexts for use by professionals, managers,
      policy-makers and researchers.

PMID- 17174017
TI  - A comparative analysis of the use of maternal health services between teenagers
      and older mothers in sub-Saharan Africa: evidence from Demographic and Health
      Surveys (DHS).
AB  - This paper uses Demographic and Health Surveys data from 21 countries in sub
      Saharan Africa to examine the use of maternal health services by teenagers. A
      comparison of maternal health care between teenagers and older women, based on
      bivariate analysis shows little variation in maternal health care by age.
      However, after controlling for the effect of background factors such as parity,
      premarital births, educational attainment and urban/rural residence in a
      multivariate analysis, there is evidence that teenagers have poorer maternal
      health care than older women with similar background characteristics. The results
      from multilevel logistic models applied to pooled data across countries show that
      teenagers are generally more likely to receive inadequate antenatal care and have
      non-professional deliveries. An examination of country-level variations shows
      significant differences in the levels of maternal health care across countries.
      However, there is no evidence of significant variations across countries in the
      observed patterns of maternal health care by maternal age. This suggests that the
      observed patterns by maternal age are generalizable across the sub-Saharan Africa
      region.

PMID- 17174018
TI  - Association between obsessive-compulsive disorder and a variable number of tandem
      repeats polymorphism in intron 2 of the serotonin transporter gene.
AB  - BACKGROUND: Pharmacological studies indicate a dysregulation of the serotonergic
      system in obsessive-compulsive disorder (OCD). A variable number tandem repeats
      (VNTR) polymorphism with three alleles (Stin2.9, Stin2.10, Stin2.12) has been
      described in intron 2 of the serotonin transporter (5-HTT) gene. This
      polymorphism has been associated with unipolar depression, bipolar disorder,
      schizophrenia, and anxiety disorders including OCD. METHODS: The association
      between OCD and the polymorphism is examined in 97 OCD patients, 578 psychiatric
      controls and 406 healthy controls, all Spanish Caucasians. RESULTS: Genotype
      frequencies for the polymorphism were significantly different in OCD patients,
      psychiatric patients and controls. There was a significant excess of 12/12 and
      12/10 genotypes in OCD patients compared to psychiatric patients and controls.
      CONCLUSIONS: Our results indicate a possible association between the Stin2.12
      allele of the VNTR polymorphism and OCD.

PMID- 17174019
TI  - Apoptotic related biochemical changes in human amnion cells induced by
      tributyltin.
AB  - Tributyltin (TBT) is one of the environmental pollutants, which is mostly
      accumulated in marine animals. The toxic effects of TBT have been extensively
      documented in several types of cells, but the molecular mechanisms responsible
      for TBT-induced cell damage are still not fully elucidated. The present study was
      undertaken to evaluate the apoptotic related biochemical changes in human amnion
      cells induced by TBT. After cells were exposed to TBT at the concentrations of 1
      4 microM for 2h, the results suggested that TBT could induce an early and typical
      apoptosis, moreover caspase-3, the modifications of cytoskeletal structure and
      the Bcl-2 family were involved in this process. The results will deepen our
      understanding about the toxic mechanism of TBT on human amnion cells.

PMID- 17174020
TI  - Evaluation of the enamel etching capacity of six contemporary self-etching
      adhesives.
AB  - OBJECTIVES: The purpose of this study was to evaluate the capacity of six
      contemporary self-etch primers/adhesives to demineralize ground enamel by means
      of ultrastructural analysis of the etching surface under SEM and by spectroscopic
      measurement of the percentage of calcium and phosphate ions dissolved. METHODS:
      Seventy non-carious extracted human third molars were sub-divided into 2 groups
      of 35 teeth each. The teeth of the first group were ground to expose flat,
      polished enamel surfaces 3-4mm thick. The samples thus obtained were treated with
      six self-etch bonding systems and a phosphoric acid gel (control group). The self
      etch priming agent was then eliminated and the etched enamel surface observed by
      SEM. From the teeth of the second group, disc-shaped specimens were made from
      ground enamel and subjected to application of each of the six self-etchants. Once
      the etching product had been rinsed off, the rinse solution was analyzed by
      atomic flame spectroscopy to evaluate the percentage of calcium and phosphate
      ions dissolved. RESULTS: SEM images show that AdheSE, Adper Prompt L-Pop and Xeno
      III, despite having a less intensive etching efficacy than phosphoric acid, gave
      a regular pattern over a considerable surface area and depth. iBond and One-Up
      Bond F gave less regular demineralization. For Clearfil SE Bond, the
      demineralization was ineffective. Results of the percentage of mineral loss show
      that Adper Prompt L-Pop and Xeno III were the most efficient self-etch products.
      AdheSE, iBond and One-Up Bond F, respectively exhibited decreasing demineralizing
      capacity. Clearfil SE Bond, however, gave low proportions of calcium and
      phosphate ions loss and was considered unsatisfactory. CONCLUSION: The action on
      enamel was not the same for all self-etch systems tested. The etching potential
      of the self-etch adhesives was lower than that of phosphoric acid but some self
      etch systems, particularly those with monomers containing phosphate derivatives,
      gave results close to those obtained with phosphoric acid.

PMID- 17174021
TI  - Epidemiology and outcomes of out-of-hospital cardiac arrest in Rochester, New
      York.
AB  - OBJECTIVE: To characterize out-of-hospital cardiac arrest (OHCA) and factors that
      affect survival in a medium sized city that uses system status management for
      dispatch. METHODS: A retrospective cohort study of all adult OHCA patients
      treated by EMS between 1998 and 2001 was conducted using Utstein definitions. The
      primary endpoint was 1-year survival. RESULTS: Of the 1177 patients who
      experienced OHCA during the study period, 539 (46%) met inclusion criteria. Age
      ranged from 18 to 98 years (median 67). The median call-response interval was 5
      min (range 0-21), and 93% were 9 min or less. There was no significant difference
      in the median call-response intervals between call location zip (Post) codes
      (p=0.07). Twenty percent of experienced ROSC (95% CI 17-23), 7% survived more
      than 30 days (95% CI 5-9%), and 5% survived to 1 year (95% CI 3-7%). In bivariate
      analysis, first rhythm and bystander CPR affected survival to 1 year. There was
      no significant difference in survival between male (4%) and female (7%), black
      (4%) and white (6%), or witnessed (7%) and unwitnessed arrest (4%). Logistic
      regression identified younger age, CPR initiated by bystander (19%) or first
      responder (41%), and presenting rhythm of VF/VT (32%) as factors associated with
      survival to 1 year. CONCLUSIONS: This study finds a 5% survival to 1 year among
      OHCA patients in Rochester, NY. A presenting rhythm of VF/VT and bystander CPR
      were associated with increased survival.

PMID- 17174022
TI  - Prognostic markers for bladder cancer--are we there yet?

PMID- 17174023
TI  - Relationship between age at diagnosis and clinicopathologic features of renal
      cell carcinoma.
AB  - OBJECTIVES: To analyse the influence of age at diagnosis on tumour
      characteristics and cancer-specific survival in renal cell carcinoma (RCC).
      METHODS: Data on age, tumour characteristics, and survival for 4774 patients from
      12 European RCC databases were recorded. Patients were divided into four groups
      according to age at diagnosis: < or =40, >40 and <60, > or =60 and <80, and > or
      =80 yr. The following variables were analysed: TNM stage, Fuhrman grade, tumour
      size, symptoms at diagnosis, ECOG performance status (PS), and cancer-specific
      survival. The groups were compared for usual clinical and pathologic variables,
      and cancer-specific survival. RESULTS: The four groups accounted for 288 (6%),
      1839 (38.5%), 2499 (52.3%), and 148 cases (3.2%), respectively. Differences were
      found among groups for tumour stage, symptoms at diagnosis, ECOG PS, Fuhrman
      grade (p<0.001), tumour size, M stage, and histologic subtype (p: 0.02). Patients
      < or =40 yr were more likely to have papillary or chromophobe RCCs and less
      likely to have clear-cell RCCs. No significant difference was found among groups
      for N stage (p: 0.15). The 5-yr cancer-specific survival rates for the four age
      categories were 85%, 74%, 70%, and 69%, respectively. In multivariate analysis
      age category remained an independent prognostic parameter (p<0.001). CONCLUSIONS:
      Renal tumours diagnosed in younger age are characterized by lower tumour stages
      and grades as well as favourable histologic patterns compared with tumours in
      older patients. Basic research is required for explaining such a relationship
      between age, tumour aggressiveness, and therefore tumour biology.

PMID- 17174024
TI  - New method for calculating densities of nitroaromatic explosive compounds.
AB  - A new model has been introduced for simple calculation of crystal density of an
      important class of organic explosives, namely nitroaromatic energetic compounds.
      This model is based on the fundamental correlation. The introduced procedure has
      been applied to 60 well-known and new synthesized organic nitroaromatic
      explosives. The results show that the present method gives comparable prediction
      respect to well-developed group additivity method for estimation of crystal
      density of organic explosives. The introduced simple method can be applied to any
      complex nitroaromatic explosive that contains the elements of carbon, hydrogen,
      nitrogen and oxygen with no difficulties.

PMID- 17174025
TI  - Effects of pH and temperature on isotherm parameters of chlorophenols biosorption
      to anaerobic granular sludge.
AB  - As the most important parameters affecting the biosorption, pH and temperature
      were studied in this paper in order to more completely understand their effects
      on chlorophenols' biosorption onto anaerobic granular sludge. Sorption isotherms
      of 4-chlorophenol (4-CP) and 2,4-dichlorophenol (2,4-DCP) at various temperatures
      were determined; the data of 4-CP could be simulated by Langmuir model, while the
      data of 2,4-DCP could only be reproduced by Freudlich equation. The uptake
      capacity of 4-CP and 2,4-DCP could reach 1.5mgg(-1) and 5.04mgg(-1) when 2,4-DCP
      concentration was 90mgL(-1) and 4-CP concentration was 107mgL(-1), respectively.
      2,4-DCP was more strongly adsorbed onto the anaerobic granular sludge than 4-CP,
      which might be correlated with the numbers of chlorine substitute. The
      Experiments studying pH effects showed that the adsorption capacity of 4-CP and
      2,4-DCP was quite pH dependent and increased with decrease in pH.

PMID- 17174026
TI  - Organochlorine and organophosphoric insecticides, herbicides and heavy metals
      residue in industrial wastewaters in Cyprus.
AB  - Most industries in Cyprus possess permits either for disposal at central
      wastewater treatment plants (the treated effluent of which is reused or disposed
      into the sea), or discharge on soil, or reuse either for irrigation or
      groundwater recharge or discharge into the sea. A preliminary investigation
      undertaken by the University of Cyprus in regards to dangerous substances was the
      first step towards establishing a new licensing and monitoring system. Liquid
      liquid extraction was used for the extraction of the selected pesticides from
      wastewaters. Gas chromatography with two different detection methods (ECD and
      FTD) was applied for the determination of 17 pesticides (12 organochlorine
      insecticides, 3 organophosphoric insecticides and 2 herbicides). In addition ICP
      and a mercury evaporation unit were used to determine the concentrations of heavy
      metals in the samples. The results revealed the presence of several priority
      substances in wastewaters, in most cases at concentrations well below the
      regulatory limits. Non-compliance was observed for a limited number of metals.
      Sixteen out of 17 organic substances that were monitored for 1-year period time
      were traced in different wastewater streams. What was found out is that there is
      a need to expand the analytical determinations and the monitoring to more
      wastewater streams and more priority substances, in order to safeguard the water
      resources in Cyprus.

PMID- 17174028
TI  - Assessing the effect of verbal working memory load on visuo-spatial exogenous
      orienting.
AB  - The aim of this study was to assess whether or not loading verbal working memory
      (WM) affects the exogenous orienting of visuo-spatial attention. Visuo-spatial
      exogenous orienting was measured under low/high WM load conditions by means of an
      orthogonal spatial cuing paradigm. Participants had to discriminate the elevation
      (up versus down) of a visual target preceded by a peripheral spatially
      nonpredictive visual cue presented on either the left or right. This elevation
      discrimination task was carried out in-between a verbal WM test, in which a
      sequence of six digits (to be remembered for report at the end of the trial) was
      presented either in numerically ascending or random order (i.e., low and high
      load conditions, respectively). Participants made significantly more recall
      errors in the high load than in the low load condition, demonstrating that the
      verbal WM load manipulation had been effective. However, WM load did not interact
      with visuo-spatial exogenous orienting (i.e., comparable cuing effects were
      reported in both load conditions). These results are consistent with the view
      that peripheral visual onsets automatically capture spatial attention, regardless
      any concurrent increase of verbal WM load.

PMID- 17174027
TI  - Mesopontine cholinergic projections to the hypoglossal motor nucleus.
AB  - Mesopontine cholinergic (ACh) neurons have increased discharge during
      wakefulness, rapid eye movement (REM) sleep, or both. Hypoglossal (12)
      motoneurons, which play an important role in the control of upper airway patency,
      are postsynaptically excited by stimulation of nicotinic receptors, whereas
      muscarinic receptors presynaptically inhibit inputs to 12 motoneurons. These data
      suggest that ACh contributes to sleep/wake-related changes in the activity of 12
      motoneurons by acting within the hypoglossal motor nucleus (Mo12), but the
      origins of ACh projections to Mo12 are not well established. We used retrograde
      tracers to assess the projections of ACh neurons of the mesopontine
      pedinculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei to the
      Mo12. In six Sprague-Dawley rats, Fluorogold or B subunit of cholera toxin, were
      pressure injected (5-20nl) into the Mo12. Retrogradely labeled neurons,
      identified as ACh using nitric oxide synthase (NOS) immunohistochemistry, were
      found bilaterally in discrete subregions of both PPT and LDT nuclei. Most
      retrogradely labeled PPT cells (96%) were located in the PPT pars compacta region
      adjacent to the ventrolateral tip of the superior cerebellar peduncle. In the
      LDT, retrogradely labeled neurons were located exclusively in its pars alpha
      region. Over twice as many ACh neurons projecting to the Mo12 were located in the
      PPT than LDT. The results demonstrate direct mesopontine ACh projections to the
      Mo12. These projections may contribute to the characteristic of wakefulness and
      REM sleep increases, as well as REM sleep-related decrements, of 12 motoneuronal
      activity.

PMID- 17174029
TI  - Pyruvate slows disease progression in a G93A SOD1 mutant transgenic mouse model.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      caused by selective motor neuron death, and currently no effective treatment is
      available for ALS. In this study, we investigated the neuroprotective effects of
      pyruvate, which acts as an anti-oxidant and as an energy source. We treated G93A
      SOD1 transgenic mice with pyruvate (from 70 days of age, i.p., at 1000
      mg/kg/week), and found that it prolonged average lifespan by 12.3 days (10.5%),
      slowed disease progression, and improved motor performance, but did not delay
      disease onset. Pyruvate treatment was also associated with reduced nitrotyrosine
      immunoreactivity, gliosis, and increased Bcl-2 expression in the spinal cords of
      G93A SOD1 transgenic mice. These results suggest that pyruvate treatment may be a
      potential therapeutic strategy in ALS.

PMID- 17174030
TI  - Efficient in vitro amplification of a mouse-adapted scrapie prion protein.
AB  - Protein misfolding cyclic amplification (PMCA) is a highly sensitive technique
      used to detect minute amounts of scrapie prion protein (PrP(Sc)), a major protein
      component of the infectious agents associated with prion diseases. Although
      exponential in vitro amplification of hamster scrapie PrP(Sc) has been
      established, the PMCA used was unsuccessful in achieving good amplification of
      PrP(Sc) from other animals. Here, we have investigated the cause of the
      insufficient PrP(Sc) amplification in mice and have developed an improved method
      suitable for amplification of the PrP(Sc) of the mouse-adapted scrapie prion
      strain Chandler. Mouse PrP(C), the cellular form of the prion protein, tends to
      become resistant to proteases during incubation independent of sonication. By
      adding digitonin to the reaction buffer as a lipid detergent, accumulation of the
      protease-resistant PrP(C) was inhibited; hence, mouse PrP(Sc) could be amplified
      to infinite levels. The present study is the first report describing effective
      amplification of PrP(Sc) of the mouse-adapted scrapie prion and this improved
      PMCA technique will contribute to prion research that uses mice as experimental
      animals.

PMID- 17174031
TI  - Perception of longitudinal body axis in microgravity during parabolic flight.
AB  - It has been proposed that an internal representation of body vertical has a
      prominent role in spatial orientation. This investigation investigated the
      ability of human subjects to accurately locate their longitudinal body axis (an
      imaginary straight body midline running from head to toes) while free-floating in
      microgravity. Subjects were tested in-flight, as well as on ground in normal
      gravity in both the upright and supine orientations to provide baseline
      measurements. The subjects wore a goggle device and were in total darkness. They
      used knobs to rotate two luminous lines until they were parallel to the
      subjective direction of their longitudinal body axis, in the roll (right/left)
      and the pitch (forward/backward) planes. Results showed that the error between
      the perceived and the objective direction of the longitudinal body axis was
      significantly larger in microgravity than in normal gravity. This error in this
      egocentric frame of reference is presumably due to the absence of somatosensory
      cues when free-floating. Mechanical pressure on the chest using an airbag reduced
      the error in perception of the longitudinal body axis in microgravity, thus
      improving spatial orientation.

PMID- 17174032
TI  - First detection of olfactory marker protein (OMP) immunoreactivity in the
      olfactory epithelium of a cartilaginous fish.
AB  - Olfactory marker protein (OMP) is a protein expressed in the mature olfactory and
      vomeronasal neurons of many vertebrates, such as mammals, amphibians and bony
      fishes. Aim of this work was to investigate the OMP expression in the olfactory
      epithelium of the shark Scyliorhinus canicula (Linnaeus, 1758), by
      immunohistochemistry (IHC). Immunoreactivity was detected in the olfactory
      receptor neurons, in the crypt neurons and in the nerve fibers below the
      epithelium. Although very little is known about the OMP's function, its
      involvement in synaptogenesis, transduction cascade, neurogenesis and development
      of olfactory system has been suggested. The present work shows for the first time
      OMP's presence in a cartilaginous fish.

PMID- 17174033
TI  - A complete analysis of the laser beam deflection systems used in cantilever-based
      systems.
AB  - A working model has been developed which can be used to significantly increase
      the accuracy of cantilever deflection measurements using optical beam techniques
      (used in cantilever-based sensors and atomic force microscopes), while
      simultaneously simplifying their use. By using elementary geometric optics and
      standard vector analysis it is possible, without any fitted or adjustable
      parameters, to completely and accurately describe the relationship between the
      cantilever deflection and the signal measured by a position sensitive photo
      detector. By arranging the geometry of the cantilever/optical beam, it is
      possible to tailor the detection system to make it more sensitive at different
      stages of the cantilever deflection or to simply linearize the relationship
      between the cantilever deflection and the measured detector signal. Supporting
      material and software has been made available for download at
      http://www.physics.mun.ca/beauliu_lab/papers/cantilever_analysis.htm so that the
      reader may take full advantage of the model presented herein with minimal effort.

PMID- 17174034
TI  - Comparative serological diagnosis of toxoplasmosis in horses using locally
      isolated Toxoplasma gondii.
AB  - A total of 420 serum samples collected from horses of different ages, sexes and
      breeds, located at some horse farms in Egypt, were used for serological studies.
      A crude antigen of the locally isolated Toxoplasma gondii tachyzoites from horse
      tissues (LA) was used for the detection of T. gondii antibodies in horses. It
      showed good diagnostic efficiency (38.1%) by Enzyme Linked Immunosorbent Assay
      (ELISA). To increase this efficiency, an affinity purification process was
      performed. Two fractions were obtained from LA by CNBr-Sepharose 4B affinity
      column chromatography named; unbound (LAunb) and bound (LAb). LAb showed the
      highest diagnostic potency (51.7%), while LAunb showed the lowest value (31.7%)
      using ELISA. The electrophoretic profile of LA (12 bands), LAb (6 bands) and
      LAunb (6 bands) showed molecular weights ranged from 25.1 to 184.3kDa. The
      immunoreactive bands of each of the three antigens were identified with infected
      horse sera by immunoblot assay. Four immunogenic bands of 155.8, 115.1, 83.2 and
      66.2kDa were identified in LAb and probably were responsible for the highest
      diagnostic potency. Examination of horse sera by Indirect Fluorescence Antibody
      Test (IFAT) at a dilution of 1: 64 and Modified Agglutination Test (MAT) at a
      dilution of 1: 25 revealed that 170 (40.5%) and 202 (48.1%) had antibodies
      against T. gondii, respectively. The current research introduces crude and
      purified fractions (bound and unbound) obtained from the locally isolated
      tachyzoites (equine origin), which are utilized globally for the first time in
      detection of T. gondii antibodies in horses. Furthermore, this study recommended
      utilization of the bound fraction in diagnosis of toxoplasmosis using indirect
      ELISA which proved better diagnostic potency compared with IFAT and MAT.

PMID- 17174035
TI  - Infection of sandflies by a cat naturally infected with Leishmania infantum.
AB  - Despite the recent reports of feline leishmaniosis from Southern Europe, cats are
      still regarded as unusual Leishmania hosts. A cat found chronically infected with
      Leishmania was submitted to xenodiagnosis. After being sedated, the animal was
      exposed to the bite of 100 laboratory-reared Phlebotomus perniciosus in a fine
      net cage for 90 min. Four out of 19 blood-fed sandflies (21%) showed motile
      promastigotes at the dissection. Parasites cultured from cat's lymph node and an
      infected fly were identical at PCR-RFLP genotyping and identified as Leishmania
      infantum MON-1, the main zymodeme responsible for human and canine leishmaniosis
      in Southern Europe. This is the first evidence of transmissibility of feline
      parasites to a proven vector, suggesting that cats may represent an additional
      domestic reservoir for L. infantum.

PMID- 17174036
TI  - Pathways between ecstasy initiation and other drug use.
AB  - This study aims to shed light on drug use pathways associated with ecstasy use
      initiation. Data from 54,573 respondents aged 12-21 years old from the 2002-2003
      National Survey on Drug Use and Health (NSDUH) public use data files were
      analyzed via Cox proportional hazards models with time-dependent covariates. Our
      findings showed that marijuana, cocaine, and heroin were significant independent
      predictors of subsequent ecstasy use. Earlier ecstasy initiation was
      significantly associated with subsequent other illegal drug initiation
      (marijuana, cocaine and heroin). The strength of the association was greater for
      the pathway from earlier marijuana initiation to subsequent ecstasy initiation as
      compared to the pathway in the opposite direction. The pathway from earlier
      ecstasy initiation to subsequent cocaine and heroin initiation was also stronger
      as compared to pathways in the opposite directions. Pathways between ecstasy
      initiation and marijuana, cocaine and heroin initiation seem to be independent of
      the association between drug use and psychiatric symptoms/deviant behaviors.
      Ecstasy initiation seems to play a role in the subsequent initiation of cocaine
      and heroin.

PMID- 17174037
TI  - Antiproliferative effect of polyphenols and sterols of virgin argan oil on human
      prostate cancer cell lines.
AB  - BACKGROUND: The aim of our study has to evaluate the antiproliferative effect of
      polyphenols and sterols extracted from the virgin argan oil on three human
      prostatic cell lines (DU145, LNCaP, and PC3). METHODS: Cytotoxicity, anti
      proliferative effects and nuclear morphological changes of cells were analyzed
      after treatment with sterols and polyphenols. The results were compared to 2
      methoxyestradiol (2ME(2)) as positive control. RESULTS: Polyphenols and sterols
      of virgin argan oil and 2ME(2) exhibited a dose-response cytotoxic effect and
      antiproliferative action on the three tested cell lines. The antiproliferative
      effect of polyphenols was similar for the DU145 and LNCaP cell lines; the GI(50)
      (defined as the concentration inhibiting growth by 50% in comparison with the
      control) was respectively 73 and 70microg/ml. The antiproliferative effect of
      sterols was 46 and 60microg/ml as GI(50) for the DU145 and LNCaP cell lines. For
      the PC3 cell line, the best antiproliferative effect was obtained by argan
      sterols with GI(50)=43microg/ml. On the other hand, the nuclear morphology
      analyses have shown an increased proportion of pro-apoptotic of nuclei in LNCaP
      cell treated with IC(50) of polyphenols or sterols compared to control cells. Our
      results show for the first time the antiproliferative and pro-apoptotic effects
      of polyphenols and sterols extracted from virgin argan oil and confirm the
      antiproliferative and pro-apoptotic effects of 2ME(2) on prostate cancer cell
      lines. CONCLUSION: These data suggest that argan oil may be interesting in the
      development of new strategies for prostate cancer prevention.

PMID- 17174038
TI  - Antispasmodic effects of Persea cordata bark fractions on guinea pig ileum.
AB  - The present study describes the antispasmodic activity of some fractions from the
      bark of Persea cordata, against guinea pig ileum contracted by acetylcholine and
      histamine. Hexane and dichloromethane fractions demonstrated the most promising
      biological effects, having similar potency to that of papaverine, a well-known
      antispasmodic agent.

PMID- 17174040
TI  - Progression from marijuana use to daily smoking and nicotine dependence in a
      national sample of U.S. adolescents.
AB  - BACKGROUND: While it has been demonstrated that smoking cigarettes in adolescence
      increases the likelihood of progressing to marijuana use, few studies have
      considered the reverse scenario in which early use of cannabis leads to greater
      tobacco smoking. METHODS: Participants (n=5963), who had never smoked cigarettes
      daily by wave I of the National Longitudinal Study of Adolescent Health, were
      followed 6 years (waves I-III) from adolescence into young adulthood. Measures of
      marijuana use (lifetime use, monthly use, age at first use), as assessed at wave
      I within 12-16 (n=3712) and 17-21 (n=2251) year-olds, were separately modeled as
      predictors of three tobacco-related outcomes: (1) age at onset of daily cigarette
      smoking, (2) lifetime nicotine dependence, (3) current nicotine dependence.
      RESULTS: In the older cohort (17-21-year-olds at wave I), lifetime (>10 times)
      and past-month marijuana use at wave I were predictive of an earlier initiation
      into daily cigarette smoking and a greater likelihood of developing nicotine
      dependence by wave III. Furthermore, age at first use of cannabis was negatively
      associated with risk of nicotine dependence in the older, but not younger cohort.
      CONCLUSION: After controlling for baseline measures of tobacco smoking and other
      demographic risk factors, the use of marijuana in adolescence was modestly
      associated with daily cigarette smoking and nicotine dependence in young
      adulthood.

PMID- 17174039
TI  - The Nicotine Dependence Syndrome Scale in Finnish smokers.
AB  - The Nicotine Dependence Syndrome Scale (NDSS) is a new multidimensional measure
      of nicotine dependence. The study aim was to examine the structure and
      heritability of the NDSS and its associations with nicotine dependence defined by
      FTND and DSM-IV criteria among Finnish smokers participating in an ongoing twin
      family study. Adult twin pairs concordant for smoking from the Finnish Twin
      Cohort Study, and their siblings and parents were interviewed. Among 1370
      smokers, the sum score of the NDSS (a summary measure of dependence) correlated
      moderately highly with FTND score (r=0.62). Subjects in the highest NDSS sum
      score groups were more likely to be nicotine dependent according to DSM-IV
      criteria compared with those in the lowest quintile (odds ratio=36.7, 95%
      confidence interval 13.0-103). In exploratory factor analysis, we derived three
      factors, named drive/priority, stereotypy/continuity and tolerance. The
      drive/priority factor correlated best with FTND (r=0.54). Genetic modeling showed
      no differences in the genetic architecture of NDSS or FTND by gender; the overall
      heritability estimate for NDSS was 0.30 (95% CI 0.06-0.47), and for FTND 0.40
      (95% CI 0.23-0.55). The sum score of the NDSS is moderately highly associated
      with DSM-IV nicotine dependence as well as FTND. These analyses indicate that the
      NDSS functions well in a Finnish family-based sample and provide additional
      validation of a new scale developed to capture complex behavioural features of
      nicotine dependence.

PMID- 17174041
TI  - Gender and the assessment of at-risk drinking: evidence from the GENACIS Canada
      (2004-2005) telephone survey version of the AUDIT.
AB  - The alcohol use disorders identification test (AUDIT) is widely used in general
      population surveys as a method of determining prevalence of hazardous drinking.
      However, its interpretation has been questioned particularly regarding the
      unequal contribution of the items to the total score, specifically, that the
      drinking frequency item contributes disproportionately to the score and may lead
      to inappropriate identification of some drinkers as hazardous drinkers. To
      explore these issues further as well as possible gender differences in the
      applicability of the AUDIT, we conducted analyses using a modified version of the
      AUDIT (AUDIT(M)) as part of a general population survey that used random digit
      dialing and computer-assisted telephone interviewing. Item and factor analyses
      were performed separately for men and women, and the impacts of excluding the
      frequency of drinking item in the measurement of mean scores, percentages and
      types of problems for men and women were examined. We found that the AUDIT(M)
      items loaded onto three distinct dimensions for both men and women: frequency of
      drinking; usual quantity and frequency of heavy-episodic drinking; problem
      consequences from drinking. In addition, we found that excluding the frequency
      question may give a more meaningful estimate of the percent of drinkers actually
      at risk of experiencing problems from drinking for both men and women. Finally,
      although our analyses identified only minor gender differences in the structure
      of the AUDIT and good sensitivity for identifying problem drinkers among both men
      and women, significant gender differences in the types of problems experienced
      suggest that use and interpretation of the AUDIT should routinely take gender
      into consideration.

PMID- 17174043
TI  - Effect of long-term exposure to low-level toluene on airway inflammatory response
      in mice.
AB  - Volatile organic compounds are the main substances causing multiple chemical
      sensitivity reactions in human. Our laboratory has previously showed that the
      exposure of low-level formaldehyde causes immunogenic and neurogenic inflammatory
      responses in mice. The aim of the present study was to investigate the effect of
      long-term, low-level toluene exposure on airway inflammatory responses in mice
      lung. We exposed female C3H mice to filtered air (0ppm) or 50ppm of toluene for
      6h/day on 5days/week for 6 or 12 weeks in the whole body exposure chamber. One
      day following the last toluene exposure, we collected bronchoalveolar lavage
      fluid from each mouse and examined cellular infiltration and production of
      cytokines, chemokines, neurotrophins and substance P by using ELISA method. We
      found that the number of total cells and macrophages increased significantly in
      both 6 and 12-week-exposed mice. In addition, the production of interferon-gamma
      and substance P were decreased significantly and nerve growth factor was not
      affected in both 6 and 12-week-exposed mice. In contrast, neurotrophin-3
      production in bronchoalveolar lavage fluid was significantly increased only in 12
      week-exposed mice. Our findings suggest that long-term (12-week) exposure of mice
      to low-level toluene modulates airway inflammatory response via neurological
      signaling.

PMID- 17174044
TI  - Factors governing susceptibility to chemical allergy.
AB  - Chemical allergy describes adverse health effects that result from the
      stimulation of specific immune responses by chemicals. Hypersensitivity reactions
      are the result of normally beneficial immune responses acting inappropriately
      against benign antigens, causing inflammatory reactions and tissue damage. The
      two most frequent manifestations of chemical-induced allergy are contact
      hypersensitivity and respiratory sensitization, both of which can have serious
      impact on quality of life, and represent a common occupational health problems.
      Chemical agents cause approximately 30% of cases of occupational asthma and
      roughly 90% of these cases involve immunological mechanisms (allergy). Over the
      past few decades industrialized countries have witnessed a significant increase
      (although the rate of increase has recently slowed) in the prevalence of atopic
      diseases including atopic rhinitis, bronchial asthma and urticaria. Many factors,
      both intrinsic and extrinsic, can contribute to the development of chemical
      allergy. In particular, the immune response can be affected by the genetic
      background, pathological conditions, hormonal and central nervous system status,
      etc. and by chemical related factors, e.g. dose level, frequency, route and
      duration of exposure, biotransformation, pharmacokinetics, chemical reactivity,
      etc. Furthermore, chemical pollution, indoor environment, diet, vaccination
      programs and the "hygiene hypothesis" have also been implicated in the increased
      prevalence of asthma and atopic diseases. Following the influence of condition of
      exposure, heritable and acquired factors, such as age, genetic background, gender
      etc. on chemical allergy is discussed.

PMID- 17174042
TI  - Phenotypic and genotypic characteristics of methicillin/oxacillin-resistant
      Staphylococcus intermedius isolated from clinical specimens during routine
      veterinary microbiological examinations.
AB  - Methicillin/oxacillin resistance of 10 S. intermedius strains was investigated by
      conventional and molecular methods. The strains tested had been isolated in
      Germany during routine veterinary microbiological examinations of specimens from
      a small animal clinic between May and September 2005. Epidemiological
      relationships of the strains were studied by macrorestriction analysis of their
      chromosomal DNA using pulsed field gel electrophoresis (PFGE). Species identity
      of the 10 S. intermedius strains was confirmed by conventional methods and by PCR
      mediated amplification of S. intermedius specific segments of thermonuclease
      encoding gene nuc. As controls, four methicillin/oxacillin resistant S.
      intermedius (MRSI) strains obtained from specimens sent by four veterinarians and
      three selected methicillin/oxacillin sensitive S. intermedius (MSSI), also
      obtained from the small animal clinic, were tested. The 10 strains, representing
      approximately 6% of all S. intermedius isolated from the clinic throughout the
      time period mentioned above, and the four MRSI obtained from veterinarians, were
      methicillin/oxacillin and penicillin resistant using disk diffusion tests and
      could be cultivated on oxacillin resistant screening agar base (ORSAB). Both
      resistances could be confirmed by multiplex PCR detecting the resistance genes
      mecA and blaZ. The three MSSI were methicillin/oxacillin sensitive in all tests.
      Epidemiological investigation by macrorestriction analysis of the chromosomal DNA
      of the strains by pulsed field gel electrophoresis revealed that all 10 MRSI
      strains obtained from the clinic and the four MRSI strains obtained from
      veterinarians, in contrast to the three MSSI strains, represent identical or
      closely related bacterial clones possibly indicating a cross-infection of the
      animals in the clinic and the distribution of a single MRSI clone in the pet
      population.

PMID- 17174045
TI  - Spanish post-menopausal women's viewpoints on hormone therapy.
AB  - OBJECTIVE: The purpose of this study was to identify women's socio-demographic
      and climacteric factors, as well as other variables related to health care,
      associated with the prescription of the treatment during menopause and to
      investigate the prevalence of certain conditioning factors in early
      discontinuation in women aged 40-65 years in a population of post-menopausal
      women in Spain. STUDY DESIGN: Cross-sectional survey. SETTING: Four of the most
      inhabited cities in Spain (Madrid, Barcelona, Seville and Valencia). POPULATION:
      A total of 270 symptomatic post-menopausal women. METHODS: A personal interview
      with a semi-structured questionnaire specifically designed to collect information
      on treatments for climacteric-related complaints. MAIN OUTCOME MEASURES: The
      reasons for HRT, the evaluation of alternative therapies, the reasons for
      choosing one therapy or another and reasons for discontinuation. RESULTS: Of all
      the subjects included, 180 were still taking any type of treatment and 90 were
      former HRT users or had never used HRT. Among the latter, 43% of women expressed
      fear of the side effects and 38% gave the risk of breast cancer as the main
      reason for not using HRT. Of them, 58% receive phytoestrogens. Media and negative
      data from medical journals influenced this attitude in 67% of the women. On the
      other hand, only 9.4% of HRT users were reluctant to receive the therapy and the
      main reasons for maintaining HRT were its efficacy against climacteric symptoms,
      medical prescription and life quality. CONCLUSIONS: Side effects and fear of
      cancer were the most common reasons for not using HRT; and medical prescription,
      symptomatic improvement and quality of life were the main reasons for using it.
      Negative data from journals have an important effect on women's attitudes to HRT.

PMID- 17174046
TI  - Bismuth-norfloxacin complex: synthesis, physicochemical and antimicrobial
      evaluation.
AB  - Norfloxacin is a fluoroquinolone antibacterial agent which is active against
      various Gram-positive as well as Gram-negative microorganisms. Presence of metal
      ions considerably alters the activity of fluoroquinolones against potentially
      susceptible bacteria. As bismuth is known to possess a good antibacterial
      activity, bismuth complex of norfloxacin was prepared by reacting bismuth citrate
      with aqueous solution of norfloxacin. The structure of the bismuth-norfloxacin
      complex (BNC) was confirmed by spectral, chemical and elemental analysis.
      Antimicrobial studies were carried out using agar diffusion method against
      Escherichia coli (ATCC 25922), Klebsiella pneumoniae (NTCC 10320), Staphylococcus
      aureus (ATCC 29213), Bacillus pumilis (NTCC 8241) and Staphylococcus epidermidis
      (ATCC 12228). The results showed significant increase (p<0.05, Tukeys test) in
      antibacterial activity of BNC as compared with norfloxacin and physical mixture
      of norfloxacin and bismuth citrate. This increase in activity is being considered
      due to increased bioavailability of the metal drug complex. Thus, the use of the
      BNC may be preferable over norfloxacin alone.

PMID- 17174047
TI  - A novel method for assessing inhibition of ibuprofen chiral inversion and its
      application in drug discovery.
AB  - An inhibition assay to assess the potential for chiral inversion of compounds was
      developed using R(-)-ibuprofen as the probe substrate. Inhibition of the chiral
      inversion of R(-)-ibuprofen by structurally similar compounds in cyropreserved
      rat hepatocytes was studied using chiral HPLC and LC/MS methods for the
      chromatographic separation and detection of enantiomers. Concept validation of
      this assay was performed with three commercially available compounds and four
      Pfizer compounds. The results of these studies demonstrated that compounds that
      are structurally similar to ibuprofen inhibited the formation of S(+)-ibuprofen,
      suggesting that they may undergo similar enzymatic chiral inversion pathways or
      compete for the same enzyme active sites. Additionally, an application of this
      assay in early drug discovery for a specific class of compounds was demonstrated.
      Thirty-three in-house compounds were screened for their chiral inversion
      potential utilizing this assay to investigate the structure activity relationship
      (SAR) for this class of compounds.

PMID- 17174048
TI  - In vitro formulation optimization of intranasal galantamine leading to enhanced
      bioavailability and reduced emetic response in vivo.
AB  - The purpose of the current investigation was to optimize an intranasal (IN)
      galantamine (an acetylcholinesterase inhibitor used for treatment of Alzheimer's
      disease) formulation using an in vitro tissue model, to correlate those results
      to in vivo bioavailability, and to compare emetic response to oral dosing. A
      design-of-experiments (DOE) based formulation screening employing an in vitro
      tissue model of human nasal epithelium was used to assess drug permeability,
      tight junction modulation, and cellular toxicity. In vivo studies in rats
      compared pharmacokinetic (PK) profiles of different formulations dosed
      intranasally. Finally, studies in ferrets evaluated PK and gastrointestinal (GI)
      related side effects of oral compared to nasal dosage forms. Galantamine
      permeation was enhanced without increasing cytotoxicity. Pharmacokinetic testing
      in rats confirmed the improved drug bioavailability and demonstrated an in vitro
      in vivo correlation. Compared to oral dosing, IN galantamine resulted in a
      dramatically lowered incidence of GI-related side effects, e.g., retching and
      emesis. These findings illustrate that IN delivery represents an attractive
      alternative to oral dosing for this important Alzheimer's disease therapeutic. To
      our knowledge, the data herein represent the first direct confirmation of
      reducing GI-related side effects for IN galantamine compared to oral dosing.

PMID- 17174049
TI  - The effect of terpene concentrations on the skin penetration of diclofenac
      sodium.
AB  - Terpenes and sesquiterpenes have been suggested as promising non-toxic, non
      irritating transdermal penetration enhancers. This investigation aimed to study
      the effect of terpene concentration on the transdermal absorption of diclofenac
      sodium from ethanol:glycerin:phosphate buffer solution (60:10:30). Therefore,
      enhancing effects of various terpenes (menthone, limonenoxide, carvone, nerolidol
      and farnsol) with different concentrations (0.25, 0.5, 1, 1.5 and 2.5%, v/v) on
      the permeation of diclofenac sodium were evaluated using Franz diffusion cells
      fitted with rat skin. Furthermore, solubility of diclofenac sodium in the vehicle
      in presence of different concentrations of terpenes was determined. The results
      showed that despite the negligible effect of terpenes on the drug solubility,
      there was a profound skin penetration enhancement effect, although the terpene
      enhancers varied in their ability to enhance the flux of diclofenac sodium. The
      results showed that at the highest concentration of terpene (2.5%, v/v) the rank
      order of enhancement effect for diclofenac sodium was
      nerolidol>farnesol>carvone>methone>limonenoxide, whereas at the low concentration
      of 0.25% the rank order was farnesol>carvone>nerolidol>menthone>limonenoxide. No
      direct relationship existed between terpene concentration and the permeation
      rate. The most outstanding penetration enhancer was nerolidol, providing an
      almost 198-fold increase in permeability coefficient of diclofenac sodium,
      followed by farnesol with a 78-fold increase.

PMID- 17174050
TI  - Accuracy of developing tooth length as an estimate of age in human skeletal
      remains: the deciduous dentition.
AB  - Dental age assessments are widely used to estimate age of immature skeletal
      remains. Most methods have relied on fractional stages of tooth emergence and
      formation, particularly of the permanent dentition, for predicting the age of
      infants and very young children. In this study, the accuracy of regression
      equations of developing deciduous tooth length for age estimation (Liversidge et
      al.) is tested on a sample of 30 Portuguese subadult skeletons of known age at
      death. Overall the method shows high accuracy and the average difference between
      estimated and chronological age is between 0.20 and -0.14 years when using single
      teeth, and 0.06 years, when using all available teeth. However, there is a
      tendency for the deciduous molars to provide overestimates of chronological age.
      Results show that age estimates can be obtained within +/-0.10 years with a 95%
      confidence interval when several teeth are used. Overall between-tooth agreement
      in age estimates decreases with increasing age but there is less variability of
      estimates with more teeth contributing to overall mean age. One seemingly
      limitation of this method may be the fact that it was developed by combining the
      maxillary and mandibular teeth. The other is related to the accuracy with which
      radiographic tooth length can be used as a valid surrogate for actual tooth
      length. Nevertheless, the advantages of this metric method surpass the
      limitations of chronologies based on stages of dental development.

PMID- 17174051
TI  - Kabuki syndrome with trichrome vitiligo, ectodermal defect and
      hypogammaglobulinemia A and G.
AB  - We report a unique combination of symptoms in a case of Kabuki syndrome (KS), a
      multiple malformation/mental retardation syndrome that has a prevalence of
      1:32,000 to 1:86,000. The patient was a mentally delayed 12-year-old male with
      trichrome vitiligo, ectodermal defect, and hypogammaglobulinemia A and G. This
      unique combination of signs, described here for the first time, indicates that KS
      comprises multiple deficits that affect not only the brain, but ectoderm-derived
      structures and the immune system as well. Our report may provide important clues
      for understanding the pathogenesis of the KS.

PMID- 17174052
TI  - Ribosomal proteins Rpl10 and Rps6 are potent regulators of yeast replicative life
      span.
AB  - The yeast ribosome is composed of two subunits, the large 60S subunit (LSU) and
      the small 40S subunit (SSU) and harbors 78 ribosomal proteins (RPs), 59 of which
      are encoded by duplicate genes. Recently, deletions of the LSU paralogs RPL31A
      and RPL6B were found to increase significantly yeast replicative life span (RLS).
      RPs Rpl10 and Rps6 are known translational regulators. Here, we report that
      heterozygosity for rpl10Delta but not for rpl25Delta, both LSU single copy RP
      genes, increased RLS by 24%. Deletion of the SSU RPS6B paralog, but not of the
      RPS6A paralog increased replicative life span robustly by 45%, while deletion of
      both the SSU RPS18A, and RPS18B paralogs increased RLS moderately, but
      significantly by 15%. Altering the gene dosage of RPL10 reduced the translating
      ribosome population, whereas deletion of the RPS6A, RPS6B, RPS18A, and RPS18B
      paralogs produced a large shift in free ribosomal subunit stoichiometry. We
      observed a reduction in growth rate in all deletion strains and reduced cell size
      in the SSU RPS6B, RPS6A, and RPS18B deletion strains. Thus, reduction of gene
      dosage of RP genes belonging to both the 60S and the 40S subunit affect lifespan,
      possibly altering the aging process by modulation of translation.

PMID- 17174054
TI  - Acute colonic disease: how to image in emergency.
AB  - The diseases affecting the large intestine represent a diagnostic problem in
      adult patients with acute abdomen, especially when clinical symptoms are not
      specific. The role of the diagnostic imaging is to help clinicians and surgeons
      in differential diagnosis for an efficient early and prompt therapy to perform.
      This review article summarizes the imaging spectrum of findings of colonic acute
      disease, from mechanical obstruction to inflammatory diseases and perforation,
      offering keys to problem solving in doubtful cases as well as discussing
      regarding the more indicated imaging method to use in emergency, particularly
      MDCT.

PMID- 17174055
TI  - CT colonography: results and limitations.
AB  - Meta-analysis of data from studies of CT colonography suggests that it has
      excellent per-patient average sensitivity and average specificity for detection
      of adenomatous polyps and cancer. However, while its potential as a screening
      test is undoubted, there are several current limitations that will need to be
      overcome before it can be considered seriously by health policy makers. These
      revolve around issues of generalisability, which is inhibited most by a lack of
      trained observers and access to CT scanners, and a paucity of data relating to
      cost-effectiveness. Whether offering CT colonography as an alternative to
      competing strategies will genuinely enhance compliance also needs further and
      more detailed attention.

PMID- 17174056
TI  - Validation of an in vitro method for the determination of cyanide release from
      ferric-hexacyanoferrate: Prussian blue.
AB  - Prussian blue (PB), ferric hexacyanoferrate, Fe(4)[Fe(CN)(6)](3) is indicated for
      the treatment of known or suspected internal contamination with radioactive
      cesium, radioactive thallium, or non-radioactive thallium. Owing to the molecular
      properties, cyanide is likely dissociated from PB under physiologically relevant
      pH conditions, thus raising a concern for the safety of the product. The
      objective of this study was to calibrate and validate a cyanide assay over a wide
      pH range (from 0.5 to 12) on the basis of Spectroquant cyanide test method
      (Merck). Merck's photometric method requires that the measurement solution be
      within pH 5.5-6.0, hence samples and standards need to be adjusted to this pH
      range. Since the process of pH adjustment may have significant impact on the
      determination of cyanide, the analysis method needs to be optimized, calibrated
      and validated under each pH condition in the study. The validation
      characteristics included accuracy, precision, quantification limit, linearity,
      and stability. The intra-day accuracy ranged from 90% to 109% for the deionized
      water and solutions of pH 0.5-12. The intra-day precision (R.S.D.) ranged from
      2.4% to 8.1% for the deionized water and solutions of pH 0.5-12. The analytical
      range was linear from 0.05 to 0.5 ppm (mg/L). The R(2) ranged from 0.9925 to
      0.9998. This validated method was successfully implemented to determine cyanide
      release from PB under various pH conditions (from 1.0 to 12) at different time
      points (from 1 to 24 h).

PMID- 17174053
TI  - Motor neuron targeting of IGF-1 attenuates age-related external Ca2+-dependent
      skeletal muscle contraction in senescent mice.
AB  - A population of fast muscle fibers from aging mice is dependent on external
      Ca(2+) to maintain tetanic force during repeated contractions. We hypothesized
      that age-related denervation in muscle fibers plays a role in initiating this
      contractile deficit, and that prevention of denervation by IGF-1 overexpression
      would prevent external Ca(2+)-dependent contraction in aging mice. IGF-1
      overexpression in skeletal muscle prevents age-related denervation, and prevented
      external Ca(2+)-dependent contraction in this work. To determine if the effects
      of IGF-1 overexpression are on muscle or nerve, aging mice were injected with a
      tetanus toxin fragment-C (TTC) fusion protein that targets IGF-1 to spinal cord
      motor neurons. This treatment prevented external Ca(2+)-dependent contraction. We
      also show evidence that injections of the IGF-1-TTC fusion protein prevent age
      related alterations to the nerve terminals at the neuromuscular junctions. We
      conclude that the slow age-related denervation of fast muscle fibers underlies
      dependence on external Ca(2+) to maintain tetanic force in a population of muscle
      fibers from senescent mice.

PMID- 17174057
TI  - A highly sensitive resonance Rayleigh scattering method for the determination of
      bleomycinA5 and bleomycinA2 with some halofluorescein dyes.
AB  - In a weak acidic medium, bleomycinA(5) (BLMA(5)) and bleomycinA(2) (BLMA(2)) can
      react with halofluorescein dyes such as erythrosine (Ery), eosin Y (EY), eosin B
      (EB) and Rose Bengal (RB) by virtue of electrostatic attraction and hydrophobic
      force to form ion-association complexes, which can result in the large-scale
      enhancement of resonance Rayleigh scattering (RRS) and the appearance of new RRS
      spectra. The increments of scattering intensity (Delta I) were directly
      proportional to the concentrations of bleomycin (BLM) in certain ranges. The
      detection limits for BLMA(5) and BLMA(2) ranged from 0.017 to 0.062 microg ml(
      1). The Ery system had the highest sensitivity and its detection limit (3sigma)
      was 0.017 microg ml(-1) for BLMA(5) and 0.018 microg ml(-1) for BLMA(2),
      respectively. Using Ery as a RRS probe, a new highly sensitive method for the
      determination of BLM anticancer drugs has been developed. It was applied in the
      determination of BLMA(5) and BLMA(2) in serum and urine samples. The recovery was
      from 99.0% to 103.0%. In this work, the RRS spectral characteristics of the
      binding products and the optimum conditions of the reaction were investigated.
      The mechanism of ion-association reaction and the reasons of enhancement of
      resonance light scattering were discussed.

PMID- 17174058
TI  - Determination and pharmacokinetic study of amlodipine in human plasma by ultra
      performance liquid chromatography-electrospray ionization mass spectrometry.
AB  - A novel, specific and sensitive ultra performance liquid chromatography tandem
      mass spectrometry (UPLC-MS/MS) method was developed for the determination and
      pharmacokinetic study of amlodipine in human plasma. The analysis was carried out
      on an ACQUITY UPLC BEH C(18) column (50 mm x 2.1 mm, i.d., 1.7 microm) with
      gradient elution at a flow-rate of 0.35 ml/min. The mobile phase was water and
      acetonitrile under gradient conditions (both containing 0.3% formic acid) and
      nimodipine was used as the internal standard. Detection was performed on a triple
      quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode
      via Turbo ion spray ionization (ESI). Linear calibration curves were obtained
      over the concentration range 0.15-16.0 ng/ml, with a lower limit of
      quantification of 0.15 ng/ml. The intra- and inter-day precision (R.S.D.) values
      were below 15% and the accuracy (R.E.) was -2.3% to 6.9% at all three QC levels.
      The method was used to support clinical pharmacokinetic studies of amlodipine in
      healthy volunteers following oral administration.

PMID- 17174059
TI  - Radiofrequency ablation permits an effective treatment for colorectal liver
      metastasis.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has become an important adjunct to
      modern liver surgery. However, scant knowledge on long-term outcome of RFA for
      colorectal liver metastasis is available, nowadays. METHODS: This is a
      prospective clinical study of patients with liver metastasis of colorectal cancer
      who were treated by RFA between April 1, 1998, and November 30, 2004. Forty-seven
      patients with 147 liver metastases were treated with RFA in a total of 70
      interventions. A metastasis resection was not feasible in 80% of the
      interventions. All the patients were followed up at regular intervals with
      contrast-enhanced computed tomography (CT) and laboratory tests including
      carcinoembryonic antigen (CEA). RESULTS: No RFA-related mortality occurred. The
      median follow-up time after the diagnosis of liver metastasis was 33 months. The
      RFA-related morbidity was 7%. After the RFA, the expected median overall survival
      rate is, to date, 39 months. Overall survival rates at 1, 2 and 3 years were 88%,
      80% and 57%, respectively. Local recurrence rates reached 8.8% overall and 1.6%
      for metastasis smaller than 3cm in diameter. No local recurrence occurred for
      metastasis smaller than 3cm in diameter if treated with the newest RFA device.
      CONCLUSIONS: Excellent local tumour control was achieved with radiofrequency
      ablation of small liver metastasis. The expected overall survival rate of
      patients with RFA for unresectable or non-resected colorectal liver metastasis
      improved in comparison with the survival rate reported following the natural
      course (best supportive care) or chemotherapy. The low local recurrence rate of
      metastases of less than 3cm challenges the results obtained by the more invasive
      treatment of conventional liver surgery.

PMID- 17174060
TI  - Laparoscopic wedge resection for gastric GIST: long-term follow-up results.
AB  - AIM: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal
      neoplasm of the gastrointestinal tract. Recently, many investigations have been
      conducted on various aspects of laparoscopic surgery for gastric GIST. However,
      no study has provided long-term follow up results of laparoscopic surgery for
      gastric GIST. The aims of this study were to assess the feasibility and safety of
      laparoscopic surgery for gastric GIST and to evaluate the oncologic validity of
      the procedure. MATERIALS AND METHODS: Between January 1998 and August 2005, 51
      patients with submucosal tumor of the stomach were treated by laparoscopic
      surgery at our institution. Of 51 patients, 23 patients were confirmed as gastric
      GIST by immunohistochemistry (CD 117, c-kit gene product). Patients'
      clinicopathologic characteristics, operative outcomes, postoperative
      complications, and follow-up findings were analyzed retrospectively. RESULTS: The
      mean age of patients was 59.7 years, and 12 patients were women. Twelve patients
      (47%) presented with epigastric pain. The mean tumor size was 4.2+/-2.1 cm, and
      most tumors were located in the upper stomach (52.2%). The mean operative time
      was 104.3 min. No case of open conversion, reoperation and operative mortality
      occurred in the present study. Most patients had very low and low risk (60.6%),
      while only two patients had high risk malignancy. During a median follow-up
      period of 61 months (range, 7-98 months), there have been no recurrences or
      metastases. CONCLUSION: Laparoscopic wedge resection for gastric GIST is safe,
      and oncologically and technically feasible in the hands of an experienced
      laparoscopic gastric surgeon.

PMID- 17174061
TI  - The interleukin-8 (-251A/T) polymorphism is associated with increased risk for
      oral squamous cell carcinoma.
AB  - AIMS: In light of recently found contribution of angiogenic and inflammation
      related factors to malignancies, this study investigated the possible association
      of interleukin-8 gene (IL-8) to increased risk of oral cancer. METHODS: The IL-8
      (-251 A/T) polymorphism, which influences IL-8 gene expression, was evaluated by
      restriction fragment length polymorphism analysis in DNA samples of 158 German
      and Greek patients with oral squamous cell carcinoma and 156 healthy controls of
      equivalent sex, ethnicity and age. RESULTS: Significant increase of mutant (A
      251) allele, which results in higher IL-8 gene expression, was observed in all
      patients in comparison to normal controls (P<0.001). The A/T heterozygotes had a
      two-fold greater risk (odds ratio 1.76, CI 1.11-2.79) for developing oral cancer
      compared to normal TT homozygotes. Furthermore, significantly increased values of
      mutant allele frequencies compared to controls were observed in all patients as
      well as in subgroups of patients with or without positive history of cancer
      (P<0.05 and P<0.001, respectively) and with or without positive history of
      thrombophilia (P<0.05 and P<0.001, respectively). CONCLUSIONS: In light to known
      observations of elevated plasma levels of IL-8 in several types of cancer
      including oral squamous cell carcinoma, the findings of this study suggest that
      the mutant allele of the (-251 A/T) polymorphism may be a major contributing
      genetic factor to risk for oral cancer.

PMID- 17174063
TI  - [Initial management of severe sepsis in adults and children].

PMID- 17174062
TI  - [Prehospital cricothyrotomy: a case report].
AB  - Case report of a patient with tonsillitis treated with anti-inflammatory. The
      patient presented a dyspnoea and finally a cardiac arrest. The oral intubation
      was impossible and cricothyrotomy had to be performed with a catheter over needle
      technique. We found a total airway obstruction due to an epiglottis abscess. The
      patient died few days later of sepsis. We recommend having wire-guided
      cricothyrotomy technique or catheter-over-needle technique in all prehospital
      emergency unit and having emergency physician trained to the cricothyrotomy
      technique.

PMID- 17174064
TI  - [Standard perioperative management of patients treated with lithium can lead to
      hyperosmolar coma].
AB  - A 55-year-old woman with bipolar disorder who had been taking lithium for several
      years developed hyperosmolar coma following osteosynthesis of a hip fracture. The
      coma was attributed to decompensation of undiagnosed nephrogenic diabetes
      insipidus due to chronic lithium intake. The lengthy perioperative fasting and
      large fluid loading (necessitated by the anesthetic technique) led to acute
      hypernatremia. Closer monitoring and a different anesthetic strategy might have
      avoided this classical complication of chronic lithium therapy. The patient
      recovered after symptomatic treatment. We discuss the perioperative management of
      patients taking (or having taken) lithium, based on a review of the literature.

PMID- 17174065
TI  - A BAC-based contig map of the cynomolgus macaque (Macaca fascicularis) major
      histocompatibility complex genomic region.
AB  - The construction of a cynomolgus macaque (Macaca fascicularis, Mafa) BAC library
      for genomic comparison between rhesus and cynomolgus macaques is necessary to
      promote the cynomolgus macaque as one of the important experimental animals for
      future medical and biological research. In this paper, we constructed a
      cynomolgus macaque BAC library and a map of the MHC (Mafa) genomic region for
      comparison of the genomic organization and nucleotide similarities between the
      human, the chimpanzee, and the rhesus macaque. The BAC library consists of
      221,184 clones with an average insert size of 83 kb, providing a sixfold coverage
      of the haploid genome. A total of 114 BAC clones and 54 PCR primer sets were used
      to construct a 4.3-Mb contig of the MHC region. Diversity analysis of genomic
      sequence from selected subregions of the MHC revealed that the cynomolgus
      sequence varied compared to rhesus macaque, human, and chimpanzee sequences by
      0.48, 4.15, and 4.10%, respectively. From these findings, we conclude that the
      BAC library and Mafa genomic map are useful tools for genome analysis and will
      have important applications for comparative genomics and identifying regions of
      consequence in medical research.

PMID- 17174066
TI  - Identification of corticosteroid-regulated genes in cardiomyocytes by serial
      analysis of gene expression.
AB  - Corticosteroids (aldosterone, cortisol/corticosterone) exert direct functional
      effects on cardiomyocytes. However, gene networks activated by corticosteroids in
      cardiomyocytes, as well as the involvement of the mineralocorticoid receptor (MR)
      vs the glucocorticoid receptor (GR) in these effects, remain largely unknown.
      Here we characterized the corticosteroid-dependent transcriptome in primary
      culture of neonatal mouse cardiomyocytes treated with 10(-6) M aldosterone, a
      concentration predicted to occupy both MR and GR. Serial analysis of gene
      expression revealed 101 aldosterone-regulated genes. The MR/GR specificity was
      characterized for one regulated transcript, namely ecto-ADP-ribosyltransferase-3
      (Art3). Using cardiomyocytes from GR(null/null) or MR(null/null) mice we
      demonstrate that in GR(null/null) cardiomyocytes the response is abrogated, but
      it is fully maintained in MR(null/null) cardiomyocytes. We conclude that Art3
      expression is regulated exclusively via the GR. Our study identifies a new set of
      corticosteroid-regulated genes in cardiomyocytes and demonstrates a new approach
      to studying the selectivity of MR- vs GR-dependent effects.

PMID- 17174067
TI  - Low dose nicotine treatment during early adolescence increases subsequent cocaine
      reward.
AB  - Adolescence is a critical period for the initiation of drug use, starting with
      tobacco and alcohol and progressing to marijuana and other illicit drugs. These
      findings have led to the suggestion that tobacco and alcohol are 'gateway' drugs
      that sensitize maturing reward pathways to the effects of illicit substances such
      as cocaine. To test this hypothesis, we have examined whether low-dose nicotine
      pretreatment alters acquisition of cocaine self-administration in adolescents
      more than in adults. Male and female Sprague-Dawley rats, aged postnatal day (P)
      28 or P86, were given two daily intravenous injections of nicotine (0.03
      mg/kg/0.1 ml) or saline for 4 days. At P32 and P90, rats were placed in self
      administration chambers and tested for acquisition of cocaine (0.2 or 0.5
      mg/kg/inj) for 5 days. Data were collapsed across cocaine dose and sex since
      there was no significant effect of these variables. Adolescent rats pretreated
      with nicotine exhibited significantly greater cocaine-reinforced responding as
      compared to saline controls or adults (p<0.01). This drug pretreatment effect did
      not generalize to all rewards, since nicotine did not increase responding for
      sucrose pellets in adolescents. These findings provide evidence that the
      adolescent brain is uniquely vulnerable to the effects of nicotine on subsequent
      drug reward.

PMID- 17174069
TI  - CT findings of a unicameral calcaneal bone cyst containing a fluid-fluid level.
AB  - Calcaneal unicameral bone cysts often contain fluid, but rarely contain fluid
      fluid levels. We present a case focusing on the CT findings of a large calcaneal
      bone cyst with a fluid-fluid level and a review of the literature.

PMID- 17174070
TI  - Structural determinants of LL5beta subcellular localisation and association with
      filamin C.
AB  - PI3K signalling pathways link cell surface receptors to the control of several
      intracellular functions including cell growth, survival and movement. Filamins
      are important regulators of cortical actin structure and function. LL5beta is a
      filamin binding protein that is an effector of the PI3K signalling pathway. We
      define an N-terminal region of LL5beta that is responsible for binding to the C
      terminus of filamins. Under conditions of very low PI3K activity, we show that
      this region, together with an additional domain of the protein, is responsible
      for localising the complex to punctate structures that are also decorated by L
      FILIP (a protein previously characterised to bind filamin and accelerate its
      destruction). Under conditions of significant PI3K activity, PtdIns(3,4,5)P(3)
      binding to the C-terminal PH domain in LL5beta prevents localisation to these
      structures. These observations start to define the basis for PI3K regulation of
      filamin through LL5beta.

PMID- 17174071
TI  - Repeated intracerebroventricular infusion of nicotine prevents kainate-induced
      neurotoxicity by activating the alpha7 nicotinic acetylcholine receptor.
AB  - We examined whether (-)-nicotine infusion can affect kainic acid (KA)-induced
      neurotoxicity in rats. Although treatment with a single nicotine infusion (0.5 or
      1.0 microg/side, i.c.v.) failed to attenuate KA-induced neurotoxicity, repeated
      nicotine infusions (1.0 microg/side/day for 10 days) attenuated the seizures, the
      severe loss of cells in hippocampal regions CA1 and CA3, the increase in
      activator protein (AP)-1 DNA binding activity, and mortality after KA
      administration. alpha-Bungarotoxin and mecamylamine blocked the neuroprotective
      effects of nicotine. These results suggest that repeated nicotine treatment
      provides alpha7 nicotinic acetylcholine receptor-mediated neuroprotection against
      KA toxicity.

PMID- 17174068
TI  - A developmental comparison of the neurobehavioral effects of ecstasy (MDMA).
AB  - The entactogen +/-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a
      popular recreational drug among college, high school, and, occasionally, middle
      school students. Preclinical research examining the acute and long-term effects
      of MDMA has predominately been conducted in reproductively mature subjects but
      there has been increasing interest in adolescent and in utero exposure. This
      review examines the acute and long-term responses to MDMA during perinatal,
      adolescent, and adult periods. The ability of MDMA to alter core body temperature
      emerges gradually during ontogeny while a reduction in body weight is evident at
      all ages. Learning and working-memory are also altered independent of the
      developmental stage of exposure. Current evidence suggests adults are more
      sensitive to the long-term serotonin depletions following MDMA but younger ages
      also exhibit substantial and rapid neuroplasticity. Sexually dimorphic MDMA
      responses have been identified for the acute hyperthermic and motoric effects of
      MDMA with pubescent males being especially susceptible. Several physiological,
      behavioral, and neurochemical MDMA issues requiring further study are also
      outlined.

PMID- 17174072
TI  - Asymmetric accumulation of hippocampal 7S SNARE complexes occurs regardless of
      kindling paradigm.
AB  - Modifications of neurotransmission may contribute to the synchronization of
      neuronal networks that are a hallmark of epileptic seizures. In this study we
      examine the synaptosomal proteins involved in neurotransmitter release to
      determine if alterations in their interactions correlate with the chronic
      epileptic state. Using quantitative western blotting, we measured the levels of
      7S SNARE complexes and SNARE effectors in the effected hippocampi from animals
      that were electrically kindled through stimulation from one of three different
      foci. All three kindling paradigms, amygdalar, entorhinal, and septal, were
      associated with an accumulation of 7S SNARE complexes in the ipsilateral
      hippocampus, measured 1 month after completion of kindling. Of the eight SNARE
      effectors examined (alpha-SNAP, NSF, SV2A/B, Munc18a/nSec1, Munc13-1, Complexins
      1 and 2, and synaptotagmin I), there was a statistically significant
      bihemispheric increase of hippocampal SV2 and decrease of NSF upon kindling;
      neither by itself would be expected to account for the asymmetry of SNARE complex
      distribution. These data suggest that an ipsilateral hippocampal accumulation of
      SNARE complexes is a permanent alteration of kindling-induced epilepsy,
      regardless of stimulation pathway. The significance of these findings toward a
      molecular understanding of epilepsy will be discussed.

PMID- 17174073
TI  - Significant decrease of decorin expression in human skin following short-term
      ultraviolet exposures.

PMID- 17174074
TI  - In vitro activity of tigecycline against quinolone-resistant Streptococcus
      pneumoniae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant
      enterococci.
AB  - Tigecycline is a glycylcycline with promising broad-spectrum activity, including
      resistant Gram-positive organisms. This study characterizes in vitro activity of
      tigecycline against quinolone-resistant Streptococcus pneumoniae (QRSP),
      methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
      Enterococcus faecalis (VRE). An in vitro pharmacodynamic model generated specific
      bacterial kill profiles for tigecycline against clinical isolates of QRSP, MRSA
      and VRE. Tigecycline produced a 6.6 log total reduction and cleared QRSP from the
      pharmacodynamic model by 18 h. Tigecycline and vancomycin were unable to achieve
      3-log reductions in the MRSA and VRE isolates; log reductions in MRSA and VRE
      were 1.5 and 1.2 logs for tigecycline and 2.8 and zero for vancomycin,
      respectively. Area under the concentration time curve to minimum inhibitory
      concentration (AUC/MIC) values for tigecycline ranged from 79 to 158 microg h/mL
      and tigecycline concentrations remained above the MIC (T>MIC) throughout the
      simulated dosing interval. Tigecycline showed in vitro activity against the QRSP,
      MRSA and VRE isolates studied. Low MIC values, prolonged elimination half-life
      and the associated post-antibiotic effect (PAE) observed with tigecycline are
      desirable attributes that make it a potentially attractive option for treating
      resistant Gram-positive organisms.

PMID- 17174075
TI  - Carcinogen-induced early molecular events and its implication in the initiation
      of chemical hepatocarcinogenesis in rats: chemopreventive role of vanadium on
      this process.
AB  - Carcinogen-induced formation of DNA adducts and other types of DNA lesions are
      the critical molecular events in the initiation of chemical carcinogenesis and
      modulation of such events by chemopreventive agents could be an important step in
      limiting neoplastic transformation in vivo. Vanadium, a dietary micronutrient has
      been found to be effective in several types of cancers both in vivo and in vitro
      and also possesses profound anticarcinogenicity against rat models of mammary,
      colon and hepatocarcinogenesis. Presently, we report the chemopreventive
      potential of vanadium on diethylnitrosamine (DEN)-induced early DNA damages in
      rat liver. Hepatocarcinogenesis was induced in male Sprague-Dawley rats with a
      single, necrogenic, intraperitoneal (i.p.) injection of DEN (200 mg/kg body
      weight) at week 4. There was a significant induction of tissue-specific
      ethylguanines, steady elevation of modified DNA bases 8-hydroxy-2'
      deoxyguanosines (8-OHdGs) (P<0.0001; 89.93%) along with substantial increment of
      the extent of single-strand breaks (SSBs) (P<0.0001) following DEN exposure.
      Supplementation of 0.5 ppm of vanadium throughout the experiment abated the
      formations of O(6)-ethylguanines and 7-ethylguanines (P<0.0001; 48.71% and 67.54%
      respectively), 8-OHdGs (P<0.0001; 81.37%), length:width (L:W) of DNA mass
      (P<0.01; 62.12%) and the mean frequency of tailed DNA (P<0.001; 53.58%), and
      hepatic nodulogenesis in preneoplastic rat liver. The study indicates that 0.5
      ppm vanadium is potentially and optimally effective, as derived from dose
      response studies, in limiting early molecular events and preneoplastic lesions,
      thereby modulating the initiation stage of hepatocarcinogenesis. Vanadium is
      chemopreventive against DEN-induced genotoxicity and resulting hepatocellular
      transformation in rats.

PMID- 17174076
TI  - Film/tablet adhesion, film thickness, internal stresses and bridging of the
      intagliations--a unified model with practical implications.
AB  - Building on previous work carried out over the past two decades, a unified and
      integrated model relating film/tablet adhesion, film thickness, internal stresses
      and the defect bridging of the intagliations has been developed. The model can
      explain the apparently anomalous results seen when measuring the adhesion of film
      coatings to tablet substrates as well as providing an insight into possible ways
      of preventing or minimising the incidence of bridging.

PMID- 17174077
TI  - Evidence of Oatp and Mdr1 in cryopreserved rat hepatocytes.
AB  - Transport proteins control uptake of drugs into the liver (e.g., organic anion
      transporting polypeptide (Oatp)) and excretion of drugs from the liver (e.g.,
      multidrug resistance protein 1 (Mdr1)). In this study, cryopreserved rat
      hepatocytes were used to investigate the effect of different culture conditions
      (suspension, conventional culture and sandwich culture) on the uptake of [(3)H]
      taurocholate+/-probenecid and the efflux of [(3)H]-vinblastine+/-ketoconazole;
      mRNA levels of Oatp1a1, Oatp1a4, Mdr1a and Mdr1b were determined using real-time
      reverse transcription polymerase chain reaction (RT-PCR) and protein expression
      of Mdr was assessed by immunocytochemistry. The uptake of [(3)H]-taurocholate was
      higher in cryopreserved rat hepatocytes maintained in suspension as compared to
      hepatocytes in culture. A significant time dependent decline in the uptake of
      [(3)H]-taurocholate was noticed from day 2 to day 4 in conventional and sandwich
      cultures. [(3)H]-taurocholate uptake was significantly reduced using the
      inhibitor probenecid. Oatp mRNA expression in hepatocytes in suspension was
      similar to that of liver, whereas much lower levels were detected in the
      cultures; this was in accordance with [(3)H]-taurocholate uptake results. Mdr1
      activity was assessed by accumulation of the Mdr1 selective substrate, [(3)H]
      vinblastine, in hepatocytes using ketoconazole as an inhibitor. The results
      showed Mdr1 activity in cryopreserved rat hepatocytes in conventional and
      sandwich cultures. A time dependent increase in Mdr1 activity was noticed from
      day 2 to day 4. Mdr1 activity was not found using hepatocytes in suspension. Mdr1
      mRNA expression was high in cryopreserved hepatocytes from both culture systems.
      Immunocytochemistry showed the Mdr protein in membranes of hepatocytes in culture
      as well as in that of hepatocytes in liver sections. In conclusion, the present
      study showed that cryopreserved rat hepatocytes maintained canalicular transport
      activity (Mdr1) and basolateral transport activity. Hepatocytes in suspension had
      a higher uptake of taurocholate with a high Oatp (1a1 and 1a4) mRNA expression as
      compared to hepatocytes in culture. The presence of Mdr1 in both conventional and
      sandwich culture was confirmed at mRNA level, by protein expression as well as
      transport activity.

PMID- 17174078
TI  - [Early neonatal presentation to the pediatric emergency department, Brazzaville
      (Congo)].
AB  - OBJECTIVES: To identify and analyze factors influencing the readmission of
      newborns to the paediatric emergency unit of university hospital of Brazzaville
      after their stay in maternity. MATERIAL AND METHODS: A prospective survey was
      conducted in newborns discharged from maternity for household, excluding infants
      delivered by caesarean section. RESULTS: A total of 458 (6.3%) newborns were
      recruited among 7233 children admitted in the paediatric emergency unit. The
      visits took place between 8 am-1 pm (51.7%), 14 pm-19 pm (31.7%) and 20 pm-7 am
      (16.4%). Visit motives were cough, fever, digestive signs, and malformations.
      Main causes of hospitalization were severe sepsis (21.8%), bronchopulmonary
      infections (23.0%), isolated fever (12.6%), malformations (5.3%). Low bith weight
      newborns and newborns with shorter length of stay at maternity (less than 24 h)
      were most often hospitalized than infants with normal weight (P < 0.01).
      CONCLUSION: Increased length of hospitalization in maternity, systematic medical
      examination of newborn in maternity, better information of mothers on
      breastfeeding, and improved health care should contribute to decrease the
      rehospitalization rate during the first month of life.

PMID- 17174079
TI  - Formation of filopodia in earthworm (Lumbricus terrestris) coelomocytes in
      response to osmotic stress.
AB  - Coelomocytes, the immunodefense cells of the earthworm Lumbricus terrestris, are
      exposed to changing osmotic pressures as the worm's coelomic fluid responds to
      fluctuating wet-dry conditions of the surrounding soil. Using light and
      fluorescence microscopy combined with actin and tubulin disrupting drugs, we
      determined the effects of changing osmotic pressure on coelomocyte morphology.
      The coelomocytes from L. terrestris respond to an increase in environmental
      osmotic pressure from isotonic conditions (170 mOsm) to hypertonic conditions
      (715 mOsm) by changing from a round/petalloid morphology to a filopodial
      morphology. Cytoskeletal fluorescent staining studies indicate that for filopodia
      to form, the actin cortical ring, present in most coelomocytes in isotonic
      conditions, must be disrupted. Breakdown of the actin ring by exposure to a
      hypertonic environment or actin disrupting drugs allows the formation of actin or
      tubulin-based filopodia. The filopodia, or podial-like extensions formed by
      earthworm coelomocytes, may enable the cells to better explore their environment.

PMID- 17174081
TI  - Gene expression profiling of differentiating embryonic stem cells expressing
      dominant negative fibroblast growth factor receptor 2.
AB  - Embryonic stem (ES) cells are derived from the inner cell mass of the blastocyst
      and can be cultured as three-dimensional embryoid bodies (EBs) in which embryonic
      pregastrulation stages are faithfully mimicked. Fibroblast growth factor
      receptors (mainly FGFR2) are involved in the first differentiation events during
      early mammalian embryogenesis. It has been demonstrated that the presence of
      FGFR2 is a prerequisite for laminin-111 and collagen type IV synthesis and
      subsequently basement membrane formation in EBs. To identify genes that are
      influenced by FGFR signalling, we performed global gene expression profiling of
      differentiating EBs expressing dominant negative FGFR2 (dnFGFR2), acquiring an
      extensive catalogue of down- and up-regulated genes. We show a strong down
      regulation of endodermal and basement membrane related genes, which strengthen
      the view that the FGFR signalling pathway is a main stimulator of basement
      membrane synthesis in EBs. We further present down-regulation of genes previously
      not linked to FGFR signalling, and in addition an active transcription of some
      mesodermal related genes in differentiating dnFGFR2 EBs.

PMID- 17174082
TI  - Skeletal muscle structure and function in response to electrical stimulation in
      moderately impaired COPD patients.
AB  - STUDY OBJECTIVE: To determine the structural and functional consequences of high
      frequency neuromuscular electrical stimulation (hf-NMES) in a group of moderately
      impaired outpatients with chronic obstructive pulmonary disease (COPD). DESIGN: A
      prospective, cross-over randomized trial. SETTING: An university-based, tertiary
      center. PATIENTS AND MATERIALS: Seventeen patients (FEV(1)=49.6+/-13.4%
      predicted, Medical Research Council dyspnoea grades II-III) underwent 6-weeks hf
      NMES (50Hz) and sham stimulation of the quadriceps femoris in a randomized, cross
      over design. Knee strength was measured by isokinetic dynamometry (peak torque)
      and leg muscle mass (LMM) by DEXA; in addition, median cross-sectional area (CSA)
      of type I and II fibres and capillary-fibre ratio were evaluated in the vastus
      lateralis. The 6-min walking distance (6MWD) was also determined. RESULTS: At
      baseline, patients presented with well-preserved functional capacity, muscle
      strength and mass: there was a significant relationship between strength and type
      II CSA (P<0.05). NMES was not associated with significant changes in peak torque,
      LMM or 6MWD as compared to sham (P>0.05). At micro-structural level, however,
      electrical stimulation increased type II, but decreased type I, CSA; no change,
      however, was found in the relative fibre distribution or capillary:fibre ratio
      (P<0.05). There was no significant association between individual changes in
      structure and function with training (P>0.05). Post-NMES increase in type II CSA
      was inversely related to baseline mass and strength (P<0.05). CONCLUSION: NMES
      may promote a modest degree of type II muscle fibre hypertrophy in COPD patients
      with well-preserved functional status. These micro-structural changes, however,
      were not translated into increased volitional strength in this sub-population.

PMID- 17174084
TI  - Swine manure composting by means of experimental turning equipment.
AB  - The purpose of research was to test the effectiveness of a prototype of a turning
      machine and to evaluate the feasability of a farm-scale composting process of the
      solid fraction of swine manure. A qualitative evaluation of the process and final
      product was made by monitoring the following parameters: process temperature,
      oxygen concentration inside the biomass, gaseous emissions (CH4, CO2, NH3, N2O),
      respiration index, humification index, total and volatile solids, carbon and
      nitrogen, pH and microbial load. The prototype proved to be very effective from a
      technical-operational point of view. The composting process exhibited a typical
      time-history, characterised by a thermophilic phase followed by a curing phase
      [Chiumenti, A., Chiumenti, R., Diaz, L.F., Savage, G.M., Eggerth, L.L.,
      Goldstein, N., 2005. Modern Composting Technologies. BioCycle-JG Press, Emmaus,
      PA, USA]. Gas emissions from compost the windrow were more intense during the
      active phase of the process and showed a decreasing trend from the thermophilic
      to the curing phase. The final compost was characterized by good qualitative
      characteristics, a significant level of humification [Rossi, L., Piccinini, S.,
      1999. La qualita agronomica dei compost derivanti da liquami suinicoli.
      (Agronomic quality of swine manure compost). L'informatore Agrario 38, 29-31] and
      no odor emissions. This method of managing manure represents an effective, low
      cost approach that could be an interesting opportunity for swine farms.

PMID- 17174083
TI  - Rehabilitation and the single cell.
AB  - Cellular damage triggers rapid resealing of the plasma membrane and repair of the
      cortical cytoskeleton. Plasma membrane resealing results from calcium-dependent
      fusion of membranous organelles and the plasma membrane at the site of the
      damage. Cortical cytoskeletal repair results from local assembly of actin
      filaments (F-actin), myosin-2 and microtubules into an array that closes around
      the original wound site. Control of the cytoskeletal response is exerted by local
      activation of the small GTPases, Rho and Cdc42. Recent work has given insight
      into both the membrane fusion and cytoskeletal responses to plasma membrane
      damage and we propose that Rho GTPase activation results at least in part from
      the events that drive membrane repair.

PMID- 17174085
TI  - Analysis of cholinesterase binding to a carnitine-modified EQCM sensor.
AB  - A sensor for cholinesterases (ChEs) has been developed by binding carnitine via
      1,6-diaminohexane to a mixed monolayer of 11-mercaptoundecanoic acid/11-mercapto
      1-undecanol on the surface of a gold-coated quartz crystal. Catalytically active
      and organophosphate-inhibited acetyl- and butyryl-cholinesterases of different
      origins were tested for their binding ability to D- and L-carnitine,
      respectively. The binding constants were calculated by using a one-to-one binding
      model. Additionally, the activity of the immobilized ChE was monitored and the
      operational stability was investigated amperometrically.

PMID- 17174086
TI  - A coulometric biosensor to determine hydrogen peroxide using a monomolecular
      layer of horseradish peroxidase immobilized on a glass surface.
AB  - A biosensor to detect hydrogen peroxide, by coulometry, down to submicromolar
      concentration using a monomolecular layer of horseradish peroxidase was
      developed. In this device 0.3 pmol of the enzyme were covalently immobilized on
      the glass surface of the biosensor and the enzyme layer was characterized by
      atomic force microscopy and activity measurements. The glass surface bearing the
      peroxidase was faced to a carbon electrode in a cell of 1 microl of active
      volume. The polarization of the working electrode at -100 mV versus Ag/AgCl, in
      the presence of 1,4-hydroquinone as mediator, allowed the fast reduction of the
      injected hydrogen peroxide via the hydroquinone-peroxidase system. This device
      permitted to measure the total number of H(2)O(2) molecules present in the cell
      in the concentration range of 0.3-100 microM H(2)O(2), with a sensitivity of 196
      nC/microM H(2)O(2), which is close to the theoretical value (193 nC/microM).

PMID- 17174087
TI  - Novel genomic rearrangements in the BRCA1 gene detected in Greek breast/ovarian
      cancer patients.
AB  - The identification of genomic rearrangements in breast/ovarian cancer families
      has widened the mutational spectrum of the BRCA1 gene, increasing the number of
      patients who can benefit from molecular screening. More than 60 different BRCA1
      genomic rearrangements with mapped breakpoints have been reported up to date, in
      all exons of the gene. The proportion of BRCA1 mutations due to genomic
      rearrangements varies from 8 to 27% in different populations, probably due to
      both ethnic diversity and the technical approach employed. In order to estimate
      the contribution of BRCA1 genomic rearrangements to hereditary breast/ovarian
      cancer (HBOC) predisposition in Greek families, probands from 95 families with
      breast/ovarian history but negative for point mutations or small
      insertions/deletions in BRCA1 and BRCA2 genes, were screened using Quantitative
      Multiplex PCR of Short Fluorescent Fragments (QMPSF). Two large deletions of 4.2
      and 4.4 kb were identified in exons 20 and 24 respectively. Additional screening,
      using diagnostic primers for the above deletions in exons 20 and 24, performed on
      another 86 probands from families with breast/ovarian cancer history and 210
      cases of sporadic breast/ovarian cancer resulted in the identification of two
      more large genomic rearrangements. One, identified in a familial case, identical
      to the previous exon 24 deletion and a second, identified in a case reported as
      sporadic, 3.2 kb deletion involving exon 20 and reported elsewhere in another
      Greek patient. Three out of four genomic rearrangements described in this study
      were detected in patients who had developed both breast and ovarian cancer; thus
      suggesting a correlation between the specific phenotype and the high probability
      of detecting inherited rearrangements in BRCA1.

PMID- 17174088
TI  - Lead removal through biological sulfate reduction process.
AB  - The feasibility of lead removal through biological sulfate reduction process with
      ethanol as electron donor was investigated. Sulfide-rich effluent from biological
      process was used to remove lead as lead sulfide precipitate. The experiments were
      divided into two stages; Stage I startup and operation of sulfidogenic process in
      a UASB reactor and Stage II lead sulfide precipitation. In Stage I, the COD:S
      ratio was gradually reduced from 15:1 to 2:1. At the COD:S ratio of 2:1,
      sulfidogenic condition was achieved as identified by 80-85% of electron flow by
      sulfate reducing bacteria (SRB). COD and sulfate removal efficiency were
      approximately 78% and 50%, respectively. In Stage II, the effluent from UASB
      reactor containing sulfide in the range of 30-50 mg/L and lead-containing
      solution of 45-50 mg/L were fed continuously into the precipitation chamber in
      which the optimum pH for lead sulfide precipitation of 7.5-8.5 was maintained. It
      was found that lead removal of 85-95% was attained.

PMID- 17174089
TI  - Synthesis and activity of Combretastatin A-4 analogues: 1,2,3-thiadiazoles as
      potent antitumor agents.
AB  - A series of 4,5-disubstitute-1,2,3-thiadiazole compounds were designed and
      synthesized as potent anticancer agents, some of them exhibited excellent in
      vitro and in vivo inhibitory activity.

PMID- 17174090
TI  - Synthesis and structure-activity relationship of N-acyl-Gly-, N-acyl-Sar- and N
      blocked-boroPro inhibitors of FAP, DPP4, and POP.
AB  - The structure-activity relationship of various N-acyl-Gly-, N-acyl-Sar-, and N
      blocked-boroPro derivatives against three prolyl peptidases was explored. Several
      N-acyl-Gly- and N-blocked-boroPro compounds showed low nanomolar inhibitory
      activity against fibroblast activation protein (FAP) and prolyl oligopeptidase
      (POP) and selectivity against dipeptidyl peptidase-4 (DPP4). N-Acyl-Sar-boroPro
      analogs retained selectivity against DPP4 and potent POP inhibitory activity but
      displayed decreased FAP inhibitory activity.

PMID- 17174091
TI  - Novel pyrazolopiperazinone- and pyrrolopiperazinone-based MCH-R1 antagonists.
AB  - The synthesis and biological testing of novel classes of potent melanin
      concentrating hormone (MCH-R1) antagonists based on pyrazolopiperazinone and
      pyrrolopiperazinone scaffolds are described.

PMID- 17174092
TI  - Carbonic anhydrase activators: an activation study of the human mitochondrial
      isoforms VA and VB with amino acids and amines.
AB  - The mitochondrial isozymes of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VA
      and hCA VB, were investigated for activation with a series of amino acids and
      amines. D-His, L-DOPA, histamine, dopamine, and 4-(2-aminoethyl)morpholine were
      excellent hCA VA activators, with KAs in the range of 10-130 nM. Good hCA VB
      activating effects were identified for L-His, D-Phe, D-DOPA, L-Trp, L-Tyr,
      serotonin, and 2-(2-aminoethyl)-pyridine, with KAs in the range of 44-110 nM. All
      these activators enhanced kcat, having no effect on KM, favoring thus the rate
      determining step in the catalytic cycle, the proton transfer reactions between
      the active site and environment. The activation pattern of the two mitochondrial
      isoforms is very different from each other and as compared to those of the
      cytosolic isoforms hCA I and II.

PMID- 17174093
TI  - IART: intraoperative avidination for radionuclide treatment. A new way of partial
      breast irradiation.
AB  - A new procedure, known as Intraoperative Avidination for Radionuclide Therapy
      (IART), is described in breast cancer patients. In this paper, we provide proof
      of the principle that intraoperative injection of avidin in the tumour bed after
      quadrantectomy allows homing in of intravenously (IV) administered radioactive
      biotin to the target site. This approach of targeted therapy consists of two
      steps: (i) "avidination" of the anatomical area of the tumour with avidin
      injected by the surgeon, into and around the tumour bed; (ii) targeting the
      anatomical area of the tumour by IV injection of radiolabelled biotin. The
      scintigraphic images demonstrated fast and stable uptake of labelled biotin at
      the site of operated breast. The radiation dose released to the index quadrant
      was more than 5 Gy/GBq, consistent with a boost of 20 Gy for an activity of 3.7
      GBq 90Y-biotin (100mCi). A further large clinical trial facing IART in
      combination with reduced external-beam radiotherapy is, in our opinion, fully
      justified.

PMID- 17174094
TI  - The PHD finger protein VRN5 functions in the epigenetic silencing of Arabidopsis
      FLC.
AB  - Vernalization, the acceleration of flowering by the prolonged cold of winter,
      ensures that plants flower in favorable spring conditions. During vernalization
      in Arabidopsis, cold temperatures repress FLOWERING LOCUS C (FLC) expression in a
      mechanism involving VERNALIZATION INSENSITIVE 3 (VIN3), and this repression is
      epigenetically maintained by a Polycomb-like chromatin regulation involving
      VERNALIZATION 2 (VRN2), a Su(z)12 homolog, VERNALIZATION 1 (VRN1), and LIKE
      HETEROCHROMATIN PROTEIN 1. In order to further elaborate how cold repression
      triggers epigenetic silencing, we have targeted mutations that result in FLC
      misexpression both at the end of the prolonged cold and after subsequent
      development. This identified VERNALIZATION 5 (VRN5), a PHD finger protein and
      homolog of VIN3. Our results suggest that during the prolonged cold, VRN5 and
      VIN3 form a heterodimer necessary for establishing the vernalization-induced
      chromatin modifications, histone deacetylation, and H3 lysine 27 trimethylation
      required for the epigenetic silencing of FLC. Double mutant and FLC misexpression
      analyses reveal additional VRN5 functions, both FLC-dependent and -independent,
      and indicate a spatial complexity to FLC epigenetic silencing with VRN5 acting as
      a common component in multiple pathways.

PMID- 17174096
TI  - Integration of nutritional and stress signaling pathways by Maf1.
AB  - Repression of RNA polymerase III transcription under many conditions requires
      Maf1, a yeast protein with close sequence homologs in all eukaryotes. Three
      recent studies have identified key aspects of Maf1 regulation, which suggest that
      Maf1 integrates the responses from convergent nutritional and stress signaling
      pathways. These new findings indicate that the opposing actions of protein kinase
      A and protein phosphatase 2A alter the phosphorylation state of Maf1 and thereby
      regulate its localization and repressing activity.

PMID- 17174095
TI  - CK2 Is a component of the KSR1 scaffold complex that contributes to Raf kinase
      activation.
AB  - Kinase Suppressor of Ras (KSR) is a molecular scaffold that interacts with the
      core kinase components of the ERK cascade, Raf, MEK, and ERK and provides spatial
      and temporal regulation of Ras-dependent ERK cascade signaling. In this report,
      we identify the heterotetrameric protein kinase, casein kinase 2 (CK2), as a new
      KSR1-binding partner. Moreover, we find that the KSR1/CK2 interaction is required
      for KSR1 to maximally facilitate ERK cascade signaling and contributes to the
      regulation of Raf kinase activity. Binding of the CK2 holoenzyme is constitutive
      and requires the basic surface region of the KSR1 atypical C1 domain. Loss of CK2
      binding does not alter the membrane translocation of KSR1 or its interaction with
      ERK cascade components; however, disruption of the KSR1/CK2 interaction or
      inhibition of CK2 activity significantly reduces the growth-factor-induced
      phosphorylation of C-Raf and B-Raf on the activating serine site in the negative
      charge regulatory region (N-region). This decrease in Raf N-region
      phosphorylation further correlates with impaired Raf, MEK, and ERK activation.
      These findings identify CK2 as a novel component of the KSR1 scaffolding complex
      that facilitates ERK cascade signaling by functioning as a Raf family N-Region
      kinase.

PMID- 17174097
TI  - Strategies and results of field emission scanning electron microscopy (FE-SEM) in
      the study of parasitic protozoa.
AB  - Field emission scanning electron microscopy (FE-SEM) provides a range of
      strategies for investigating the structural organization of biological systems,
      varying from isolated macromolecules to tissue organization and whole organisms.
      This review covers some of the results so far obtained using FE-SEM observation
      and various protocols of sample fixation to analyze the structural organization
      of parasitic protozoa and their interaction with host cells. The employment of FE
      SEM can be broadened through the use of gold-labeled molecules or tracers,
      gradual extraction by detergents, and cleavage techniques. These analyses provide
      significant contributions to the characterization of these organisms concerning
      ultrastructure, cytoskeleton, motility and intracellular behavior.

PMID- 17174098
TI  - A new binary compound for the production of 124I via the 124Te(p,n)124I reaction.
AB  - The binary compound, aluminum telluride (Al(2)Te(3)), was investigated as a
      target material for the production of (124)I by way of the (124)Te(p,n)(124)I
      reaction on a low-energy cyclotron. The high melting point and formation of a
      glassy matrix upon heating provided a stable target material at irradiations up
      to 20 microA of 11 MeV protons. The 87% tellurium mass fraction and 95% iodine
      separation yield led to significantly higher quantities of iodine compared to
      traditional TeO(2)/6%Al(2)O(3) admixtures. Radiochemical analysis of distilled
      samples using ion chromatography showed that the product remained in the iodide
      form while supported in weak buffer solutions. Stable Te impurities in the
      radioiodine product were less than 0.5 microg following purification by ion
      exchange chromatography. Average thick target yields of 229+/-18 microCi/microAh
      were achieved, and typical production runs at 18 microA for three hours yielded
      12 mCi at the end-of-bombardment. Total losses of the target material after each
      irradiation and distillation cycle were approximately 2%.

PMID- 17174100
TI  - Fractional flow reserve of pedicled internal thoracic artery and saphenous vein
      grafts 6 months after bypass surgery.
AB  - BACKGROUND: Although the internal thoracic artery was proven superior to
      saphenous vein graft in long-term patency, it is thought to be a more resistive
      conduit than the vein graft. Moreover, patency studies comparing both left and
      right internal thoracic arteries have provided results favoring the former.
      Fractional flow reserve is an established functional index of coronary blood
      flow. METHODS: To compare the fractional flow reserve between both internal
      thoracic arteries and saphenous vein grafts, 43 bypass grafts were studied 6
      months after revascularization. Intra-graft pressures were measured during
      cardiac catheterization using a pressure-wire advanced to the first distal
      anastomosis of 12 left internal thoracic arteries (ITAs), 10 right ITAs and of 21
      vein grafts. Pressure gradients between the aorta and the graft were measured at
      baseline and during a maximal hyperemia. RESULTS: At baseline, pressure gradient
      was recorded in the left ITA (2.9+/-2.2 mmHg), in the right ITA (1.2+/-1.2 mmHg)
      and in the vein graft (0.4+/-0.7 mmHg). During maximal hyperemia, pressure
      gradient increased to 9.6+/-3.2 mmHg in left ITA, to 4.5+/-2.0 mmHg in the right
      ITA (p<0.001 vs left ITA) and to 3.3+/-2.7 mmHg in vein (p<0.001 vs left ITA; NS
      vs right ITA). Fractional flow reserve was 0.90+/-0.04 in left ITA, 0.95+/-0.03
      in right ITA (p<0.01 vs left ITA) and 0.96+/-0.03 in vein (p<0.001 vs left ITA).
      CONCLUSION: Internal thoracic arteries and saphenous vein grafts allow myocardial
      revascularization with minimal resistance to maximal blood flow. The resistance
      appears significantly higher in left ITA compared to both the right ITA and
      venous grafts.

PMID- 17174101
TI  - Estrogen receptors in neuropeptide Y neurons: at the crossroads of feeding and
      reproduction.
AB  - Hypothalamic neuropeptide Y (NPY) neurons function as physiological integrators
      in at least two different neuroendocrine systems - one governing feeding and the
      other controlling reproduction. Estrogen might modulate both systems by
      regulating NPY gene expression; it might reduce food intake by suppressing NPY
      expression, and evoke reproductive hormone surges by stimulating it. How can
      estrogen exert opposing effects in an ostensibly homogeneous NPY neuronal
      population? Recent work with immortalized NPY-producing cells suggests that the
      ratio of estrogen receptor alpha:estrogen receptor beta can determine the
      direction and temporal pattern of transcriptional responses to estrogen. Because
      this ratio might itself be physiologically regulated, these findings provide one
      explanation for multiple neuropeptidergic responses to a single steroid hormone.

PMID- 17174099
TI  - The formation of peripheral myelin protein 22 aggregates is hindered by the
      enhancement of autophagy and expression of cytoplasmic chaperones.
AB  - The accumulation of misfolded proteins is associated with various
      neurodegenerative conditions. Peripheral myelin protein 22 (PMP22) is a
      hereditary neuropathy-linked, short-lived molecule that forms aggresomes when the
      proteasome is inhibited or the protein is mutated. We previously showed that the
      removal of pre-existing PMP22 aggregates is assisted by autophagy. Here we
      examined whether the accumulation of such aggregates could be suppressed by
      experimental induction of autophagy and/or chaperones. Enhancement of autophagy
      during proteasome inhibition hinders protein aggregate formation and correlates
      with a reduction in accumulated proteasome substrates. Conversely, simultaneous
      inhibition of autophagy and the proteasome augments the formation of aggregates.
      An increase of heat shock protein levels by geldanamycin treatment or heat shock
      preconditioning similarly hampers aggresome formation. The beneficial effects of
      autophagy and chaperones in preventing the accumulation of misfolded PMP22 are
      additive and provide a potential avenue for therapeutic approaches in hereditary
      neuropathies linked to PMP22 mutations.

PMID- 17174102
TI  - Short-term efficacy of Disulfiram or Naltrexone in reducing positive urinalysis
      for both cocaine and cocaethylene in cocaine abusers: a pilot study.
AB  - Cocaine abusers frequently report taking the drug in association with alcohol.
      This combined intake leads to the synthesis of cocaethylene, an active metabolite
      with effects similar to those of cocaine, but more prolonged. Since
      pharmacological effects of cocaethylene may partially account for the habit of
      cocaine abusers to take the drug in combination with ethanol, a main therapeutic
      goal in these patients should be making body fluids negative for cocaethylene.
      This randomized controlled open study conducted on 12 subjects co-abusers of
      cocaine and alcohol, evaluates the efficacy of a 12-week pharmacological
      treatment with Disulfiram (DIS) 400mg daily or Naltrexone (NTX) 50mg daily
      associated with Cognitive Behaviour Therapy (CBT), as compared to CBT alone, in
      terms of: (i) stay in treatment; (ii) drug-free urinalyses for cocaine and
      cocaethylene; (iii) reduction of alcohol and cocaine craving. Data presented in
      this study are restricted to the first 4 weeks of treatment when all the enrolled
      subjects were still available for examination. In fact, of the 12 subjects
      enrolled in the study only 4 (33%) completed the 12-week treatment. Of these,
      three were in the CBT group and one in the NTX/CBT group. Results show that CBT
      treated subjects remained in treatment longer than those assigned to either
      DIS/CBT or NTX/CBT therapies. However, during the first 4 weeks of treatment, CBT
      group urine tested positive almost always for both cocaine and cocaethylene. In
      contrast, both DIS/CBT and NTX/CBT treatments were associated to a statistically
      significant reduction, of positive urinalysis for both cocaine and cocaethylene,
      with respect to CBT alone. Moreover, across the first 4 weeks of treatment
      DIS/CBT and NTX/CBT treated subjects maintained lower scores at Visual Analogue
      Scales (VAS) for both cocaine and alcohol craving than subjects receiving CBT
      alone. This pilot study suggests that the transient efficacy of pharmacological
      treatments in maintaining subjects drug free, does not add to the capability of
      CBT to retain them in treatment.

PMID- 17174103
TI  - Observation of zwitterion formation in the gas-phase H/D-exchange with CH(3)OD:
      solution-phase structures in the gas phase.
AB  - Infrared spectroscopy of gas-phase singly deuterated [Trp + K](+) (formed by H/D
      exchange with CH(3)OD) shows that some (approximately 20%) kinetically stable
      zwitterionic (ZW) conformer is formed, based on the diagnostic antisymmetric CO
      stretch of the deprotonated carboxylate moiety, upsilon(as)(CO(2)(-)), at 1680
      cm(-1). A majority of the deuterated [Trp + K](+) is found to be in the charge
      solvation (CS) conformation, with deuterium exchange occurring on both the acid
      and amino groups, which is consistent with H/D scrambling. Interestingly, H/D
      exchange with the more basic ND(3) reagent did not result in the stabilization of
      a kinetically stable zwitterion, although it is not clear yet what causes this
      observation. The result for CH(3)OD shows that H/D exchange can in fact alter the
      structure of the analyte and, hence, care needs to be taken when interpreting gas
      phase H/D exchange studies. Moreover, this result shows the possibility of
      forming solution-phase structures that are thermodynamically disfavored in the
      gas phase, thus opening a new area of study.

PMID- 17174104
TI  - Modeling non-random deletions in cancer.
AB  - Chromosome deletions do abound in cancer and are detected in certain regions in a
      non-random manner. Although their relevance remains elusive, it is a general
      agreement that segmental losses provide the cell with selective growth advantage.
      Consequently these may contain genes and/or regulatory sequences that control
      normal growth and inhibit malignancy. We have developed a monochromosomal hybrid
      based experimental model for the generation and functional analysis of deletions,
      that is called "elimination test" (Et). Focused on human chromosome 3 - that was
      known to carry multiple 3p deletions - the Et was expected to restrict a 3p tumor
      suppressor region to a sufficiently small segment that permits the selection of a
      critically important candidate gene. Surprisingly, we detected three regions that
      were lost in all or majority of tumors: CER1 (3p21.3, Mb: 43.32-45.74), CER2
      (3p22, Mb: 37.83-39.06) and FER (3p14.3-p21.2, Mb: 50.12-58.03). In contrast a
      3q26-qter region (CRR) was regularly retained. CER1 - our main focus - contains
      multiple genes that may inhibit tumor growth, but 3 genes, RIS1, LF (LTF) and
      LIMD1 have already the necessary experimental support to be considered bona fide
      tumor suppressors. Tumor suppressor region borders display instability features
      including: (1) they break in evolution and in tumors, (2) they evolve
      horizontally, and (3) they are enriched with pseudogene insertions. The most
      remarkable features at the breakpoint cluster regions were segmental duplications
      that drive horizontal evolution and contribute to cancer associated instability.

PMID- 17174105
TI  - Generation and characterization of proteolytically active and highly stable
      truncated and full-length recombinant West Nile virus NS3.
AB  - West Nile virus is a medically significant emerging pathogen for which there is
      no effective antiviral therapy. The viral protease encoded by NS2B and NS3 is an
      attractive target for development of an inhibitor and has been the focus of
      numerous studies. Most have employed recombinant proteases based on an expression
      strategy we developed which links the essential hydrophilic cofactor domain
      within NS2B to the NS3 protease domain by a flexible glycine linker. However,
      autoproteolysis has been a significant problem associated with this construct.
      The recently resolved crystal structure of the cofactor bound WNV NS3 protease
      for example, was found to be truncated by 18 residues at its N-terminus. In this
      study, the autocatalytic cleavage site was identified and removed along with
      nonessential regions of the glycine linker and cofactor domain. In addition, the
      optimal size of the NS3 protease was defined. Based on this optimized construct,
      a recombinant protease incorporating the full length of NS3 was also successfully
      expressed and purified. Somewhat surprisingly, comparative analysis of the
      proteolytic activity of this recombinant with that of the protease domain alone
      revealed little influence of the C-terminal two thirds of NS3 on substrate
      binding. These modifications have yielded highly stable and constrained
      recombinant proteases, which are more suitable than existing constructs for both
      activity and structural studies.

PMID- 17174106
TI  - Low-energy-loss electron microscopy of doxorubicin in human breast cancer MCF-7
      cells: localization by color.
AB  - The distribution of the anti-cancer drug doxorubicin (DOX) in human breast cancer
      MCF-7 cells was imaged directly by low-energy-loss electron microscopy (EM)
      without specific antibodies or heavy metal stains, using only the electron
      induced molecular orbital excitation of the drug. Cells treated with DOX were
      examined live by confocal fluorescence microscopy and as very thin sections in an
      electron microscope equipped with an electron energy filter having an energy
      resolution of 1 eV. The distribution of DOX obtained by EM from pairs of images
      at energy losses of 3+/-1 eV and 10+/-1 eV agreed with fluorescence microscope
      observations, but provided much more detail, easily distinguishing localization
      between nuclear membrane and perimembrane compartments and between vacuolated
      nucleoli and perinucleolar chromatin. Treatment times up to 1h and DOX
      concentrations up to 30 microM indicated a progression of DOX ingress from higher
      concentrations in the nuclear membrane to labeling of the nucleolus. Subsequently
      DOX moved into perinucleolar chromatin and concentrated in perimembrane chromatin
      aggregations. Quantification of the DOX signal indicated a decay half-life of 320
      e/A2 under electron irradiation, whereas each image at 3000 x required 10 e/A2.
      The results point to a new field of high resolution microanalysis: color electron
      microscopy.

PMID- 17174107
TI  - The effects of electrode placement and innervation zone location on the
      electromyographic amplitude and mean power frequency versus isometric torque
      relationships for the vastus lateralis muscle.
AB  - The purposes of this investigation were to examine the effects of electrode
      placement and innervation zone (IZ) location on: (a) the torque-related patterns
      of responses for absolute and normalized electromyographic (EMG) amplitude and
      mean power frequency (MPF) and (b) the mean absolute and normalized EMG amplitude
      and MPF values. In addition, the present study examined the variability between
      subjects for the location of the IZ for the vastus lateralis (VL). Eight men
      (mean+/-SD age=23.0+/-4.3yr) performed submaximal to maximal isometric muscle
      actions of the dominant leg extensors. During each muscle action, fifteen
      channels of bipolar surface EMG signals were detected from the vastus lateralis
      using a linear electrode array aligned with the long axis of the muscle fibers.
      The results indicated that there were differences among channels 1-15 for the
      patterns of responses and mean values for absolute and normalized EMG amplitude
      and MPF versus isometric torque. Thus, normalized EMG amplitude and MPF values
      from different individuals cannot be compared if the EMG signals were detected
      from different locations over the muscle. In addition, absolute and relative (to
      femur length) estimates of IZ location for the VL resulted in similar inter
      subject variability.

PMID- 17174108
TI  - Molecular phylogenetics in Hydra, a classical model in evolutionary developmental
      biology.
AB  - Among the earliest diverging animal phyla are the Cnidaria. Freshwater polyps of
      the genus Hydra (Cnidaria, Hydrozoa) have long been of general interest because
      different species of Hydra reveal fundamental principles that underlie
      development, differentiation, regeneration and also symbiosis. The phylogenetic
      relationships among the Hydra species most commonly used in current research are
      not resolved yet. Here we estimate the phylogenetic relations among eight
      scientifically important members of the genus Hydra with molecular data from two
      nuclear (18S rDNA, 28S rDNA) and two mitochondrial (16S rRNA, cytochrome oxidase
      subunit I (COI)) genes. The phylogenetic trees obtained by maximum parsimony
      (MP), maximum likelihood (ML) and Bayesian inference (BI) methods were generally
      compatible with present morphological classification patterns. However, the
      present analysis also bears on several long-standing questions about Hydra
      systematics and reveals some characteristics of the phylogenetic relationships of
      this genus that were unknown so far. It indicates that Hydra viridissima, the
      only species in Hydra, which contains symbiotic algae, might be considered as the
      sister group to all other species within this genus. Analyses of both nuclear and
      mitochondrial sequences support the view that Hydra oligactis and Hydra
      circumcincta are sisters to all other Hydra species. Unexpectedly, we also find
      that in contrast to its initial description, the strain used for making
      transgenic Hydra, Hydra vulgaris (strain AEP) is more closely related to Hydra
      carnea than to other species of Hydra.

PMID- 17174109
TI  - Phylogeny of the Procyonidae (Mammalia: Carnivora): molecules, morphology and the
      Great American Interchange.
AB  - The Procyonidae (Mammalia: Carnivora) have played a central role in resolving the
      controversial systematics of the giant and red pandas, but phylogenetic
      relationships of species within the family itself have received much less
      attention. Cladistic analyses of morphological characters conducted during the
      last two decades have resulted in topologies that group ecologically and
      morphologically similar taxa together. Specifically, the highly arboreal and
      frugivorous kinkajou (Potos flavus) and olingos (Bassaricyon) define one clade,
      whereas the more terrestrial and omnivorous coatis (Nasua), raccoons (Procyon),
      and ringtails (Bassariscus) define another clade, with the similar-sized Nasua
      and Procyon joined as sister taxa in this latter group. These relationships,
      however, have not been tested with molecular sequence data. We examined procyonid
      phylogenetics based on combined data from nine nuclear and two mitochondrial gene
      segments totaling 6534bp. We were able to fully resolve relationships within the
      family with strongly supported and congruent results from maximum parsimony,
      maximum likelihood, minimum evolution, and Bayesian analyses. We identified three
      distinct lineages within the family: a (Nasua, Bassaricyon) clade, a
      (Bassariscus, Procyon) clade, and a Potos lineage, the last of which is sister to
      the other two clades. These findings, which are in strong disagreement with prior
      fossil and morphology-based assessments of procyonid relationships, reemphasize
      the morphological and ecological flexibility of these taxa. In particular,
      morphological similarities between unrelated genera possibly reflect convergence
      associated with similar lifestyles and diets rather than ancestry. Furthermore,
      incongruence between the molecular supermatrix and a morphological character
      matrix comprised mostly of dental characters [Baskin, J.A., 2004. Bassariscus and
      Probassariscus (Mammalia, Carnivora, Procyonidae) from the early Barstovian
      (Middle Miocene). J. Vert. Paleo. 24, 709-720] may be due to non-independence
      among atomized dental characters that does not take into account the high
      developmental genetic correlation of these characters. Finally, molecular
      divergence dating analyses using a relaxed molecular clock approach suggest that
      intergeneric and intrageneric splits in the Procyonidae mostly occurred in the
      Miocene. The inferred divergence times for intrageneric splits for several genera
      whose ranges are bisected by the Panamanian Isthmus is significant because they
      suggest diversification well precedes the Great American Interchange, which has
      long been considered a primary underlying mechanism for procyonid evolution.

PMID- 17174110
TI  - Phylogenetic diversity of the intracellular symbiont Wolbachia in termites.

PMID- 17174111
TI  - Post-glacial recolonization of the Great Lakes region by the common gartersnake
      (Thamnophis sirtalis) inferred from mtDNA sequences.
AB  - Pleistocene events played an important role in the differentiation of North
      American vertebrate populations. Michigan, in particular, and the Great Lakes
      region, in general, were greatly influenced by the last glaciation. While several
      hypotheses regarding the recolonization of this region have been advanced, none
      have been strongly supported. We generated 148 complete ND2 mitochondrial DNA
      (mtDNA) sequences from common gartersnake (Thamnophis sirtalis) populations
      throughout the Great Lakes region to evaluate phylogeographic patterns and
      population structure and to determine whether the distribution of haplotypic
      variants is related to the post-Pleistocene retreat of the Wisconsinan glacier.
      The common gartersnake was utilized, as it is believed to have been one of the
      primary vertebrate invaders of the Great Lakes region following the most recent
      period of glacial retreat and because it has been a model species for a variety
      of evolutionary, ecological, behavioral, and physiological studies. Several
      genetically distinct evolutionary lineages were supported by both genealogical
      and molecular population genetic analyses, although to different degrees. The
      geographic distribution of the majority of these lineages is interpreted as
      reflecting post-glacial recolonization dynamics during the late Pleistocene.
      These findings generally support previous hypotheses of range expansion in this
      region.

PMID- 17174112
TI  - Specific chicken repeat 1 (CR1) retrotransposon insertion suggests phylogenetic
      affinity of rockfowls (genus Picathartes) to crows and ravens (Corvidae).
AB  - While the monophyly of the order Passeriformes as well as its suborders
      suboscines (Tyranni) and oscines (Passeri) is well established, both on
      morphological and molecular grounds, lower phylogenetic relationships have been a
      continuous matter of debate, especially within oscines. This is particularly true
      for the rockfowls (genus Picathartes), which phylogenetic classification has been
      an ongoing puzzle. Sequence-based molecular studies failed in deriving
      unambiguously resolved and supported hypotheses. We present here a novel
      approach: use of retrotransposon insertions as phylogenetic markers in passerine
      birds. Chicken repeat 1 (CR1) is the most important non-LTR retrotransposon in
      birds. We present two truncated CR1 loci in passerine birds, not only found in
      representatives of Corvinae (jays, crows and allies), but also in the West
      African Picathartes species which provide new evidence for a closer relationship
      of these species to Corvidae than has previously been thought. Additionally, we
      show that not only the absence/presence pattern of a CR1 insertion, but also the
      CR1 sequences themselves contain phylogenetic information.

PMID- 17174113
TI  - Early versus late mobilization after hemiarthroplasty for proximal humeral
      fractures.
AB  - This randomized controlled trial compares 2 mobilization regimens after shoulder
      hemiarthroplasty for acute 3- and 4-part fractures. The aim was to establish
      whether the length of immobilization plays a role in the functional outcome,
      tuberosity healing, and subsequent range of motion. The same prosthesis and
      surgical technique were used. We recruited 59 patients into the study; 31 were
      randomized to early (2 weeks) mobilization and 28 to late (6 weeks) mobilization.
      Greater tuberosity migration was assessed with a series of radiographs, and the
      functional outcome was assessed with the Constant Shoulder Assessment and Oxford
      shoulder scores. Of the patients, 49 (mean age, 70 years) met the inclusion
      criteria and were followed up for 12 months. Greater tuberosity migration
      occurred in 3 cases in the early mobilization group and once in the late
      mobilization group (P > .10). There was no significant difference in the Constant
      Shoulder Assessment and Oxford scores between the 2 groups. Although there was a
      decreased incidence of tuberosity migration in the group undergoing late
      mobilization, this was not statistically significant.

PMID- 17174114
TI  - The effect of glenoid component size on the stability of total shoulder
      arthroplasty.
AB  - Frequently, during the course of total shoulder arthroplasty, the measurement of
      the patient's native glenoid is between the available prosthetic glenoid sizes.
      Technically, it may be easier for the surgeon to implant a smaller glenoid
      component. Currently, there is no information regarding the difference in joint
      stability by use of glenoid components of different sizes. Stability ratio
      measurements were performed by use of a multiaxis testing machine with 3
      different glenoid sizes (small, medium, and large) and compared by use of
      analysis of variance and the Tukey HSD test. Changes in the size of the glenoid
      component were found to have a significant effect on the stability ratio. At a
      load of 50 N, the stability ratio increased by 18% from the small to the medium
      glenoid component and by 15% from the medium to the large glenoid in the
      superoinferior axis. In the anteroposterior axis, the stability ratio increased
      by 17% from small to medium and by 10% from medium to large. The results from
      this study indicate a modest increase in stability when one chooses the larger of
      the 2 glenoid components.

PMID- 17174115
TI  - Adult-onset autosomal dominant myoclonic epilepsy: report of a family with an
      overlooked epileptic syndrome.
AB  - OBJECTIVE: Myoclonic epilepsy is a common epileptic syndrome with high genetic
      contribution. We described a pedigree in which 10 individuals presented with a
      non-progressive, adult-onset myoclonic epilepsy. MATERIALS AND METHODS: The
      pedigree was constructed and analyzed. Six affected members were studied with
      clinical grounds, mental status, neurophysiology, video-electroencephalographic
      (EEG), brain magnetic resonance imaging (MRI) and mutational analysis of GABRA1
      (GABRA1A, which endoces the alpha1 subunit of the gamma-aminobutyric acid
      receptor subtype A). Clinical and EEG data were collected from six unaffected
      members. RESULTS: Autosomal dominant hereditary was shown. The age of seizure
      onset was approximately 40. All the individuals had myoclonic seizures and a
      normal cognitive level. Bilateral symmetric jerks of the shoulders, arms or legs
      featured the myoclonic seizure. Ictally, the consciousness was not affected. The
      ictal EEG demonstrated bilateral spikes-and-waves. The occurrence of myoclonic
      seizures was not associated with sleepiness. Rare generalized tonic-clonic
      seizures occurred in two individuals. No absence or accompanying involuntary
      movements were observed. A lower dose of valproic acid (200-500 mg/D) (clonazepam
      0.5 mg/D in a patient) was required to stop the myoclonic seizures. CONCLUSIONS:
      The clinical features of late adult-onset autosomal dominant myoclonic epilepsy
      are similar to juvenile myoclonic epilepsy (JME), which is a common generalized
      epileptic syndrome with a significant hereditary component. But the age of onset,
      rare association of other seizure patterns, and non-relation of seizure onset to
      sleepiness suggest that this may be a distinct familial epileptic syndrome
      different from recognized familial myoclonic epilepsies.

PMID- 17174116
TI  - Different effects of high molecular weight sodium hyaluronate and NSAID on the
      progression of the cartilage degeneration in rabbit OA model.
AB  - OBJECTIVE: We examined the effects of nonsteroidal anti-inflammatory drug (NSAID)
      and intra-articular injections of sodium hyaluronate (HA) on cartilage
      degeneration in rabbit knee osteoarthritis (OA) model induced by partial
      meniscectomy. METHODS: Loxoprofen sodium (LOX) was used as the NSAID,
      administered p.o. once daily for 14 days at a dose of 4 mg/kg, starting from the
      day of meniscectomy. Suvenyl(SVE) was used as the high molecular weight HA,
      injected intra-articularly into injured knee every 3 days from the day of
      surgery. The effect on pain was assessed by an Incapacitance Tester, and the
      damage of cartilage was evaluated by visual assessment and histopathology at 14
      days after the surgery. RESULTS: Hind paw weight bearing on the injured paw
      decreased time-dependently in the control group. In other three groups, the
      decrease of hind paw weight distribution was suppressed, demonstrating an
      analgesic effect. Visible damage and histopathological findings of cartilage
      degeneration were evident in the cartilages of the control group at day 14. In
      the SVE group, the damaged cartilage area decreased and cartilage degeneration
      was ameliorated. In contrast, in the LOX group, the cartilage degeneration was
      augmented compared with the control group. And, this exacerbated cartilage
      degeneration induced by LOX was reversed by the concomitant use of SVE.
      CONCLUSION: Our data show that the treatment with high molecular weight HA from
      earlier stage is strongly recommended to preserve the structure of cartilage.

PMID- 17174117
TI  - Cartilage thickness in the hip joint measured by MRI and stereology--a
      methodological study.
AB  - OBJECTIVE: The purpose of this study was to develop a precise and efficient
      method for estimating the thickness of the articular cartilage in the hip joint
      and hence three different stereologic methods were tested based on Magnetic
      Resonance Imaging. DESIGN: Twenty two females and four males with hip dysplasia
      underwent MRI. The thickness of the femoral and acetabular cartilage was
      estimated. RESULTS: The results for all three methods showed that the observed
      total variance on cartilage thickness is small. The mean thickness of the
      acetabular cartilage measured by the three different methods ranged between 1.15
      mm and 1.46 mm. The mean thickness for the femoral cartilage measured by the
      three different methods ranged between 1.18 mm and 1.78 mm. The measurements took
      15-20 min per hip to carry out. CONCLUSION: Methods 1 and 3 are as precise but we
      favour method 3 because the measurements are done on images obtained through the
      center of the femoral head which means that the cartilage surface is intersected
      perpendicular and partial volume effect avoided. We suggest that this method can
      be advantageous for assessing the progression of osteoarthritis in dysplastic
      hips after periacetabular osteotomy.

PMID- 17174118
TI  - Physiological death of hypertrophic chondrocytes.
AB  - OBJECTIVE: Post-proliferative chondrocytes in growth cartilage are present in two
      forms, light and dark cells. These cells undergo hypertrophy and die by a
      mechanism that is morphologically distinct from apoptosis, but has not been
      characterized. The aims of the current study were to document the ultrastructural
      appearance of dying hypertrophic chondrocytes, and to establish a culture system
      in which the mechanism of their death can be examined. DESIGN: Growth cartilage
      from fetal and growing postnatal horses was examined by electron microscopy.
      Chondrocytes were isolated from epiphyseal cartilage from fetal horses and grown
      in pellet culture, then examined by light and electron microscopy, and
      quantitative polymerase chain reaction. RESULTS: In tissue specimens, it was
      observed that dying dark chondrocytes underwent progressive extrusion of
      cytoplasm into the extracellular space, whereas light chondrocytes appeared to
      disintegrate within the cellular membrane. Pellets cultured in 0.1% fetal calf
      serum (FCS) contained dying light and dark chondrocytes similar to those seen in
      vivo. Transforming growth factor-beta1 or 10% FCS increased the proportion of
      dark cells and induced cell death. Triiodothyronine increased the differentiation
      of dark and light cells and induced their death. Dark cells were associated with
      higher levels of matrix metalloproteinase-13 expression than light cells, and
      light cells were associated with higher levels of type II collagen expression.
      CONCLUSIONS: Light and dark hypertrophic chondrocytes each undergo a distinctive
      series of non-apoptotic morphological changes as they die. Pellet culture can be
      used as a model of the two forms of physiological death of hypertrophic
      chondrocytes.

PMID- 17174119
TI  - Ultrastructural plasticity associated with hippocampal-dependent learning: a meta
      analysis.
AB  - In order to develop a profile of how individual synapses in the hippocampal
      formation alter their structure following learning experience, a meta-analysis
      synthesized the available literature on morphological change following
      hippocampal-dependent learning. Analysis of the 132 calculated effect sizes
      suggest a consistent profile of morphological change in the hippocampus following
      learning experience. Across the hippocampal formation, dendritic complexity,
      spine density, and the size of perforated postsynaptic densities showed
      consistent increases following training. Both the density of synapses in general
      and perforated synapses in particular showed unique responses to training,
      depending on the duration of training and/or different cell layers of the
      hippocampal formation. Most importantly, it seems that this profile, while
      consistent, is small and specific--only a select few of the morphological
      parameters typically measured in anatomical studies of plasticity showed
      significant change following training. Collectively, these data suggest that the
      distinct electrophysiological properties of neocortical versus hippocampal
      synapses may be at least partially mediated by distinct morphological cascades.
      That is, on the basis of theory, and with the support of the current data, it
      seems that synaptogenesis correlates with enduring neocortical plasticity, while
      structural changes correlate with more transient hippocampal plasticity. To be
      able to state these conclusions with conviction, however, more data are needed in
      several key areas for continued pursuit of the morphological correlates of
      hippocampal-dependent learning.

PMID- 17174120
TI  - Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine
      signaling in bone marrow stromal cell niches.
AB  - In the bone marrow, the special microenvironment niches nurture a pool of
      hematopoietic stem cells (HSCs). Many HSCs reside near the vasculature, but the
      molecular regulatory mechanism of niches for HSC maintenance remains unclear.
      Here we showed that the induced deletion of CXCR4, a receptor for CXC chemokine
      ligand (CXCL) 12 in adult mice, resulted in severe reduction of HSC numbers and
      increased sensitivity to myelotoxic injury, although it did not impair expansion
      of the more mature progenitors. Most HSCs were found in contact with the cells
      expressing high amounts of CXCL12, which we have called CXCL12-abundant reticular
      (CAR) cells. CAR cells surrounded sinusoidal endothelial cells or were located
      near the endosteum. CXCL12-CXCR4 signaling plays an essential role in maintaining
      the quiescent HSC pool, and CAR cells appear to be a key component of HSC niches,
      including both vascular and endosteal niches in adult bone marrow.

PMID- 17174121
TI  - Identification of anergic B cells within a wild-type repertoire.
AB  - The contribution of anergy to silencing of autoreactive B cells in physiologic
      settings is unknown. By comparing anergic and nonanergic immunoglobulin
      transgenic mouse strains, we defined a set of surface markers that were used for
      presumptive identification of an anergic B cell cohort within a normal
      repertoire. Like anergic transgenic B cells, these physiologic anergic cells
      exhibited high basal intracellular free calcium and did not mobilize calcium,
      initiate tyrosine phosphorylation, proliferate, upregulate activation markers, or
      mount an immune response upon antigen-receptor stimulation. Autoreactive B cells
      were overrepresented in this cohort. On the basis of the frequency and lifespan
      of these cells, it appears that as many as 50% of newly produced B cells are
      destined to become anergic. In conclusion, our findings indicate that anergy is
      probably the primary mechanism by which autoreactive B cells are silenced. Thus
      maintenance of the unresponsiveness of anergic cells is critical for prevention
      of autoimmunity.

PMID- 17174122
TI  - The hematopoietic isoform of Cas-Hef1-associated signal transducer regulates
      chemokine-induced inside-out signaling and T cell trafficking.
AB  - Leukocyte migration and trafficking is dynamically regulated by various chemokine
      and adhesion molecules and is vital to the proper function of the immune system.
      We describe a role for the Cas and Hef-1-associated signal transducer in
      hematopoietic cells (Chat-H) as a critical regulator of T lymphocyte migration,
      by using lentivirus-mediated RNA interference (RNAi). Impaired migration of Chat
      H-depleted cells coincided with defective inside-out signaling shown by
      diminished chemokine-induced activation of the Rap-1 GTPase and integrin-mediated
      adhesion. Localization of Chat-H to the plasma membrane, association with its
      binding partner Crk-associated substrate in lymphocytes (CasL), and Chat-H
      mediated CasL serine-threonine phosphorylation were required for T cell
      migration. These results identify Chat-H as a critical signaling intermediate
      acting upstream of Rap1 to regulate chemokine-induced adhesion and migration.

PMID- 17174123
TI  - Dendritic cells regulate exposure of MHC class II at their plasma membrane by
      oligoubiquitination.
AB  - Dendritic cells (DCs) initiate adaptive immune responses by activating T cells
      via cognate interactions between MHC-peptide complexes and T cell receptors. In
      immature DCs, MHC class II is predominantly stored in late endocytic
      compartments, where it has a short half-life because of degradation. In contrast,
      mature DCs recruit MHC class II to the plasma membrane. We here demonstrate that
      in immature DCs, the beta-chain of MHC class II was oligoubiquitinated after
      proteolytic processing of the associated invariant chain in endosomes and that
      this modification was required for efficient endocytosis and sorting into luminal
      vesicles of multivesicular bodies. Ubiquitination of MHC class II was suppressed
      in lipopolysaccharide-activated DCs. Mutated MHC class II lacking its
      ubiquitination site was expressed at the plasma membrane, irrespective of DC
      maturation. Together, these data provide a molecular basis for the regulation of
      MHC class II-mediated antigen presentation by DCs.

PMID- 17174124
TI  - Perioperative management of a patient with Bernard-Soulier syndrome for third
      molar surgery.
AB  - Bernard-Soulier Syndrome (BSS) is a disease characterized by prolonged bleeding
      time, thrombocytopenia, and extremely large platelets and has a prevalence of
      less than 1 in 1,000,000. Patients with disorders of coagulation and bleeding can
      be among the most difficult surgical patients to manage. Perioperative hemorrhage
      can contribute to life-threatening complications in even the most routine
      surgical procedures. Because of the rarity of BSS, there are no well-defined
      protocols for the management of perioperative bleeding associated with this
      condition. Treatment with preoperative and intraoperative systemic aminocaproic
      acid, HLA-matched platelets, and topical gelfoam and thrombin resulted in
      sustained hemostasis and a durable healing response. For those rare few afflicted
      with this disease, we present a combined systemic and topical approach that may
      be helpful in the control and prevention of perioperative hemorrhage in this and
      other similar platelet disorders.

PMID- 17174126
TI  - Novel findings regarding Glut-4 expression in adipose tissue and muscle in horses
      -a preliminary report.
AB  - One of the hallmarks of insulin resistance is a reduction in glucose transporter
      4 (Glut-4) expression in adipose tissue but not in skeletal muscle. However,
      while Glut-4 has been demonstrated in skeletal and cardiac muscles in horses it
      has not been demonstrated in adipose tissue. The initial objectives of the
      present study were: (1) to test the hypothesis that Glut-4 expression would vary
      between selected key skeletal muscles; (2) to test the hypothesis that it would
      also vary between representative adipose tissue depots, and (3) to see whether
      expression would be greater in adipose tissue compared to muscle. Glut-4
      expression was determined by Western blot using samples obtained from post mortem
      biopsies obtained from four muscles (gluteus medius, semitendinosus, heart, and
      diaphragm), and four adipose tissues (subcutaneous, retroperitoneal, mesenteric,
      and omental) in three horses. There were no differences (P>0.05) in Glut-4
      protein expression between the muscles sampled. Likewise there were no
      differences (P>0.05) in Glut-4 protein expression between fat depots. There was a
      significant difference (P=0.03) when pooled means for Glut-4 expression in muscle
      (58.8+/-2.5 densitometry units) were compared with adipose tissue (115.8+/-15.7).
      This difference in Glut-4 expression in these two tissues with distinctly
      different metabolic reasons for taking up glucose may warrant further
      investigation to see if there are more pronounced differences in Glut-4
      expression in muscle and adipose tissue in various populations of horses.

PMID- 17174125
TI  - A review of TRP channels splicing.
AB  - Ion channel functional diversity can be achieved at the structural level by means
      of three main mechanisms: (1) transcriptional regulation and processing of mRNA,
      (2) heteromerization of different pore-forming channel subunits and (3)
      incorporation of regulatory subunits to the functional channel complex. In this
      review article we will focus on one of these mechanisms, alternative pre-mRNA
      splicing, in the context of the TRP superfamily of cation channels. For this
      purpose, the basic principles governing pre-mRNA splicing will be introduced and
      comprehensive tables classifying only published spliced-variants of TRP channels
      will be presented.

PMID- 17174127
TI  - Behavioral and sensory changes after direct ischemia-reperfusion injury in rats.
AB  - Complex regional pain syndromes (CRPS) are disabling pain syndromes that can
      develop after trauma or minor tissue injury affecting a limb. Characteristics of
      CRPS are sensory signs and symptoms, autonomic abnormalities, trophic changes and
      an impaired motor function. Pathophysiological mechanisms for the development of
      CRPS are still a matter of investigation. Based on clinical data and
      investigations of CRPS patients it is hypothesized that tissue hypoxia and
      inflammation are important for the development of CRPS. The aim of the current
      study was therefore to examine if direct ischemia-reperfusion injury can induce
      behavior in rats with symptoms present in patients with CRPS. After baseline
      behavior measurements the femoral artery of Wistar rats was ligated for 3h with
      consecutive reperfusion. Sham-operated rats underwent the same preparation except
      ligation of the artery. Subsequent behavioral testing (observations of
      spontaneous pain behavior, paw withdrawal to mechanical, noxious mechanical, cold
      and heat stimuli) was performed up to two months after surgery. Both in rats that
      underwent ischemia and in sham-operated rats no obvious changes of hindpaw tissue
      were observed after ischemia-reperfusion injury (trophic changes, edema,
      differences in skin color or temperature). In behavioral tests only minor changes
      were observed, these being not different between postischemic rats and sham
      operated rats. Using Wistar rats, our data do not support the idea that an
      ischemia-reperfusion injury can play a major role in the development of CRPS.

PMID- 17174128
TI  - The spinal cord connections of the myofascial trigger spots.
AB  - BACKGROUND: Recent electrophysiological studies revealed that endplate noise
      (EPN) could be specifically recorded from a myofascial trigger point (MTrP)
      region. EPN has been considered as the focal graded potentials due to excessive
      acetylcholine release in neuromuscular junction. A recent histological study has
      demonstrated a free nerve ending at the vicinity of the site, from where EPN
      could be recorded in an MTrP region. However, the sensory (afferent) and the
      motor (efferent) connections between an MTrP and the spinal cord still has never
      been fully studied. AIMS: The aim of this study was to delineate both motor and
      sensory connections between an MTrP and the spinal cord by applying the stain
      with horseradish peroxidase (HRP). METHODS: Nine Wistar rats were studied. When
      the rat was anesthetized, its biceps femoris muscles were exposed for localizing
      the myofascial trigger spot (MTrS, equivalent to MTrP in human). In one side, a
      monopolar Teflon-coated, hollow-needle electrode was used for searching EPN in an
      MTrS region, and then HRP was injected via this hollow-needle electrode into the
      site where EPN was recorded. HRP was also injected into a normal (non-taut band,
      non-MTrS) site in the contralateral side to obtain the control data. Two days
      after HRP injection, the rats were sacrificed and their spinal cords and dorsal
      root ganglia (DRG) were sectioned for the identification of the sites where
      neurons were labeled with HRP. RESULTS: The HRP-labeled neurons were found in the
      ventral horn of the spinal cord and in the DRG over L3, L4, and L5, while most
      were found in the L5 level. The mean numbers of HRP-labeled neurons in the EPN
      side looked smaller than that in the control side, but the difference did not
      reach statistically significant level (P>0.05). The mean values of the diameters
      of the HRP-labeled neurons in the DRG were not significantly different between
      the EPN side and the control side (P>0.05). However, HRP-neurons in the ventral
      horn of the spinal cord in the EPN side showed mild tendency to be smaller than
      that in the control side. CONCLUSIONS: The spinal cord connections of an MTrS are
      basically similar to that for a normal tissue region. The motor neurons related
      to MTrS tended to be smaller in their diameters. The findings in this study
      further supported the previously proposed hypotheses for the pathogenesis of an
      MTrP.

PMID- 17174129
TI  - Analytical derivation of multiple spin echo amplitudes with arbitrary refocusing
      angle.
AB  - Explicit non-recursive expressions for spin echo amplitudes have been derived for
      CPMG sequences with arbitrary refocusing flip angle.

PMID- 17174131
TI  - Quantum chemical studies on protonation of some substituted thiazole derivatives.
AB  - The acidity constants, pK(a) values for protonation of some substituted thiazole
      derivatives were calculated by using AM1 and PM3 basis sets of semi-empirical
      methods and B3LYP/6-31G(d) basis sets of density functional theory (DFT)
      calculated physical and thermodynamic parameters. Correlation search among the
      experimental and calculated acidity constants, pK(a) values, revealed that the
      best correlation exist between the experimental and ab initio calculated pK(a)
      values with a regression of R(2)=0.98.

PMID- 17174130
TI  - Using low-E resonators to reduce RF heating in biological samples for static
      solid-state NMR up to 900 MHz.
AB  - RF heating of solid-state biological samples is known to be a destabilizing
      factor in high-field NMR experiments that shortens the sample lifetime by
      continuous dehydration during the high-power cross-polarization and decoupling
      pulses. In this work, we describe specially designed, large volume, low-E 15N-1H
      solid-state NMR probes developed for 600 and 900 MHz PISEMA studies of dilute
      membrane proteins oriented in hydrated and dielectrically lossy lipid bilayers.
      The probes use an orthogonal coil design in which separate resonators pursue
      their own aims at the respective frequencies, resulting in a simplified and more
      efficient matching network. Sample heating at the 1H frequency is minimized by a
      loop-gap resonator which produces a homogeneous magnetic field B1 with low
      electric field E. Within the loop-gap resonator, a multi-turn solenoid closely
      matching the shape of the sample serves as an efficient observe coil. We compare
      power dissipation in a typical lossy bilayer sample in the new low-E probe and in
      a previously reported 15N-1H probe which uses a double-tuned 4-turn solenoid. RF
      loss in the sample is measured in each probe by observing changes in the 1H 360
      degrees pulse lengths. For the same values of 1H B1 field, sample heating in the
      new probe was found to be smaller by an order of magnitude. Applications of the
      low-E design to the PISEMA study of membrane proteins in their native hydrated
      bilayer environment are demonstrated at 600 and 900 MHz.

PMID- 17174132
TI  - Air pollutants and cough.
AB  - Epidemiological studies have shown that exposure to air pollution is associated
      with respiratory symptoms and decreases in lung function. This paper reviews
      recent literature showing that exposure to particulate matter, irritant gases,
      environmental tobacco smoke (ETS), mixed pollutants, and molds is associated with
      an increase in cough and wheeze. Some pollutants, like particulate matter and
      mixed pollutants, appear to increase cough at least as much as wheeze. Others,
      like irritant gases, appear to increase wheeze more than cough. For ETS, exposure
      during childhood is associated with cough and wheeze in adulthood, suggesting
      that the pollutant permanently alters some important aspect of the lungs, immune
      system or nervous system. We have shown in animal studies that pollutants change
      the neural control of airways and cough. Second hand smoke (SHS) exposure
      lengthened stimulated apnoea, increased the number of stimulated coughs, and
      augmented the degree of stimulated bronchoconstriction. The mechanisms included
      enhanced reactivity of the peripheral sensory neurones and second-order neurones
      in the nucleus tractus solitarius (NTS). NTS effects were due to a substance P
      mechanism at least in part. Ozone and allergen increased the intrinsic
      excitability of second-order neurones in the NTS. The animal studies suggest that
      the cough and wheeze experienced by humans exposed to pollutants may involve
      plasticity in the nervous system.

PMID- 17174133
TI  - Glycogen storage disease type Ib without hypoglycemia.

PMID- 17174134
TI  - Retinol binding protein 4 as a candidate gene for type 2 diabetes and prediabetic
      intermediate traits.
AB  - Serum retinol binding protein 4 (RBP4) was recently described as a new adipokine
      that reduced peripheral and hepatic insulin sensitivity and increased hepatic
      gluconeogenesis. The RBP4 gene maps to 10q23-24, near a region linked to T2DM in
      Caucasian and Mexican American populations. Hence, sequence variants that alter
      RBP4 expression or function could increase T2DM susceptibility and reduce insulin
      sensitivity. We screened the 6 exons, flanking intronic sequence, and 5' and 3'
      flanking sequences in 48 Caucasian and 48 African American subjects. We
      identified 21 SNPs, of which 8 were unique to the African American population.
      Additional public database SNPs were chosen for regions not screened. We selected
      SNPs for typing based on frequency, linkage disequilibrium, and location in a
      putative functional or conserved region. We typed 10 SNPs in 191 Caucasians with
      T2DM and a family history of T2DM, and 188 euglycemic controls with no family
      history of diabetes. We similarly typed 14 variants in 182 controls and 353
      diabetic individuals of African American ancestry. No single variant was
      associated with type 2 diabetes in either population (p>0.15 in African
      Americans, p>0.09 in Caucasians), but a haplotype of 8 common SNPs in Caucasians
      was significantly increased in type 2 diabetics compared with controls (0.137 vs.
      0.076, p=0.008). Furthermore, SNPs -804 and +9476 were associated with reduced
      insulin secretion, (p=0.01 and 0.001, respectively), and SNP +390 with reduced
      insulin sensitivity (p=0.0005) in Caucasians. Our data suggest that noncoding
      SNPs may increase diabetes susceptibility in Caucasians and may contribute to
      insulin resistance and reduced insulin secretion.

PMID- 17174135
TI  - Pneumoproteins as markers of paraquat lung injury: a clinical case.
AB  - OBJECTIVE: To describe the changes in lung-specific secretory proteins in
      biological fluids in a fatal case of paraquat ingestion and to present
      immunostaining data obtained on postmortem lung tissue specimens. METHODS: A 20
      year-old man committed suicide by ingesting 100ml of a 20% paraquat solution.
      Surfactant associated proteins A (SP-A), B (SP-B) and Clara cell 16kDa protein
      (CC16) were determined in the serum and on broncho-alveloar lavage performed 18h
      after admission. Renal failure progressed rapidly and the patient died from
      refractory hypoxia. Immunostaining studies using antibodies directed against
      CC16, SP-A and SP-B were performed on postmortem lung tissue specimens. RESULTS:
      Serum CC16 seemed to increase gradually with the progression of renal impairment.
      Serum SP-A and SP-B levels increased before any significant changes in pulmonary
      gas exchanges. The immunostaining study showed that the labeling for SP-A and SP
      B was reduced or absent following paraquat toxicity, while Clara cells were
      relatively preserved. CONCLUSIONS: The elevation of serum CC16 with paraquat
      toxicity is probably mainly related to a reduced renal clearance. The increase of
      serum SP-A and SP-B could reflect an increased lung to blood leakage,
      independently of the alteration of the renal function.

PMID- 17174136
TI  - RANK ligand.
AB  - RANK ligand (RANKL), a key mediator of bone resorption in normal and pathological
      states, is expressed as membrane-bound or soluble forms by tissues as diverse as
      lymph nodes, spleen, thymus and bone-forming cells. In normal bone turnover and
      in bone metastasis, RANKL stimulates the formation and activity of bone-removing
      cells, osteoclasts, by binding to its cognate receptor, RANK, on osteoclasts and
      their progenitors; these processes are disrupted by binding of RANKL to
      osteoprotegerin (OPG), a soluble decoy receptor. Whilst no mutations in the RANKL
      gene have yet been identified in human disease, mutations that result in enhanced
      RANK signalling through inactivation of OPG or activation of RANK are associated
      with Juvenile Paget's disease and familial expansile osteolysis, respectively.
      This review focuses on the central role of RANKL in bone resorption and on the
      therapeutic targeting of RANKL in osteoporosis, humoral hypercalcaemia of
      malignancy and bone metastasis.

PMID- 17174137
TI  - A model of hippocampal neurogenesis in memory and mood disorders.
AB  - The mounting evidence for neurogenesis in the adult hippocampus has fundamentally
      challenged the traditional view of brain development. The intense search for
      clues as to the functional significance of the new neurons has uncovered a
      surprising connection between neurogenesis and depression. In animal models of
      depression, neurogenesis is reduced, whereas many treatments for depression
      promote neurogenesis. We speculate on why the hippocampus, traditionally viewed
      as a memory structure, might be involved in mood disorders, and what specific
      role the new neurons might have in the pathogenesis of and recovery from
      depression. The proposed role of neurogenesis in contextual-memory formation
      predicts a specific pattern of cognitive deficits in depression and has important
      implications for treatment of this highly prevalent and debilitating disorder.

PMID- 17174138
TI  - Tagging and detection strategies for activity-based proteomics.
AB  - The field of activity-based proteomics is a relatively new discipline that makes
      use of small molecules, termed activity-based probes (ABPs), to tag and monitor
      distinct sets of proteins within a complex proteome. These activity-dependant
      labels facilitate analysis of systems-wide changes at the level of enzyme
      activity rather than simple protein abundance. While the use of small molecule
      inhibitors to label enzyme targets is not a new concept, the past ten years have
      seen a rapid expansion in the diversity of probe families that have been
      developed. In addition to increasing the number and types of enzymes that can be
      targeted by this method, there has also been an increase in the number of methods
      used to visualize probes once they are bound to target enzymes. In particular,
      the use of small organic fluorophores has created a wealth of applications for
      ABPs that range from biochemical profiling of diverse proteomes to direct imaging
      of active enzymes in live cells and even whole animals. In addition, the advent
      of new bioorthogonal coupling chemistries now enables a diverse array of tags to
      be added after targets are labeled with an ABP. This strategy has opened the door
      to new in vivo applications for activity-based proteomic methods.

PMID- 17174140
TI  - A comparison of outcomes for patients with oral squamous cell carcinoma at
      intermediate risk of recurrence treated by surgery alone or with post-operative
      radiotherapy.
AB  - Controversy remains about which patients at intermediate risk of recurrence of
      oral squamous cell carcinoma would benefit from radiotherapy. A retrospective
      review of computerised database and medical records for 462 consecutive patients
      at the Regional Maxillofacial Unit in Liverpool who were treated with primary
      surgery with or without post-operative radiotherapy was carried out. We
      classified 29% (134) of patients as being at 'low' risk of disease recurrence
      (pT1-2, N0 with clear margins), 29% (135) at 'high' risk (involved margins or
      lymph node extracapsular spread) and the remaining 42% (193) at 'intermediate'
      risk. Of those at intermediate risk, 41% (80/193) received adjuvant radiotherapy
      and their 5 year survival (SE) was 54% (6%) compared to 71% (5%) for those with
      primary surgery alone (P=0.002). A higher proportion of patients having
      radiotherapy had loco-regional recurrence (19/80 24%) compared to those treated
      by surgery alone (17/113 15%). The improved salvage rate for recurrent disease in
      the surgery alone group (8/17 53%), compared to those receiving radiotherapy
      (2/19 13%, P=0.05), indicates an advantage in withholding radiotherapy for
      patients at intermediate risk of recurrence. This study indicates a potential
      disadvantage associated with the use of postoperative radiotherapy for patients
      at intermediate risk of recurrence. A randomised trial comparing a watch and wait
      policy to postoperative radiotherapy in patients with an intermediate risk of
      recurrence is required to confirm the trend indicated in this retrospective data.

PMID- 17174139
TI  - Chemical methods for glycoprotein discovery.
AB  - An important frontier in glycoproteomics is the discovery of proteins with post
      translational glycan modifications. The first step in glycoprotein identification
      is the isolation of glycosylated proteins from the remainder of the proteome. New
      enzymatic and metabolic methods are being used to chemically tag proteins to
      enable their isolation. Once isolated, glycoproteins can be identified by mass
      spectrometry. Additional information can be obtained by using either enzymatic or
      chemoselective reactions to incorporate isotope labels at specific sites of
      glycosylation. Isotopic labeling facilitates mass spectrometry-based confirmation
      of glycoprotein identity, identification of glycosylation sites, and
      quantification of the extent of modification. By combining chemical tagging for
      isolation and isotope labeling for mass spectrometry analysis, researchers are
      developing highly effective strategies for glycoproteomics. These techniques are
      enabling cancer biologists to identify biomarkers whose glycosylation state
      correlates with disease states, and developmental biologists to characterize
      stage-specific changes in glycoprotein expression. Next-generation methods will
      make functional analyses of the glycoproteome possible, including the discovery
      of glycoprotein interaction partners and the identification of enzymes
      responsible for synthesis of particular glycan structures.

PMID- 17174141
TI  - Maspin expression in early oral tongue cancer and its relation to expression of
      mutant-type p53 and vascular endothelial growth factor (VEGF).
AB  - Even though oral tongue cancer is generally diagnosed at an early stage, the
      prognosis is poor due to frequent recurrence. Therefore, it is important to
      identify factors predictive of recurrence and to treat aggressively those
      patients with a high probability of recurrence. The relationship between
      angiogenesis and recurrence in tongue cancer has been widely investigated but no
      consensus has been reached. Mutant-type p53 and VEGF are known to be related to
      angiogenesis, and maspin is a potent angiogenic inhibitor but its role in tongue
      cancer has scarcely been examined. We observed the expression of maspin, mutant
      type p53 and VEGF by immunohistochemistry in 33 patients with stages I and II
      oral tongue cancer. And the relationships between maspin, mutant-type p53, VEGF
      expression and recurrence were analyzed. Maspin and VEGF displayed a cytoplasmic
      staining pattern and mutant-type p53 a nuclear pattern. None of expression of
      maspin, mutant-type p53, and VEGF was significantly correlated with tumor
      recurrence (p=0.34, 0.56, and 0.33, respectively) and survival. Maspin expression
      was negatively correlated with both mutant-type p53 expression (p=0.02), and VEGF
      expression (p=0.01). There was no correlation between age, sex, clinical staging,
      and recurrence. In conclusion, the expression of maspin is not related to
      recurrence of early stage oral tongue cancer. It is inversely correlated with
      that of mutant-type p53 and of VEGF, suggesting that the maspin gene is a mutant
      type p53 target in vivo and may contribute to regulate VEGF expression.

PMID- 17174142
TI  - Odontogenic keratocyst: a benign cystic neoplasm?

PMID- 17174143
TI  - Survival of second and multiple primary tumors in patients with oral cavity
      squamous cell carcinoma in the betel quid chewing area.
AB  - We report the incidence, risk factor(s), and overall survival (OS) of
      second/multiple primary tumors (SPTs/MPTs) in oral cavity squamous cell carcinoma
      (OSCC) patients in betel quid chewing areas. Of 816 untreated OSCC patients who
      had radical surgery, 15.7% had either synchronous or metachronous SPTs. The SPTs
      (70.3%) were at the oral cavity. SPTs (18.8%) developed third primary tumors,
      with a significantly higher incidence in synchromous than metachronous SPTs
      (p=0.001). An optimal, but significantly lower, 5-year OS was observed in
      patients with SPTs/MPTs than without (54.0% vs. 67.2%, p=0.0195). By multivariate
      analyses, OSCC sub-sites (p=0.006) and lymphatic permeation (p=0.040) were
      independent risk factors for SPT rate. A significantly higher 5-year OS was
      observed in SPT patients receiving a second radical surgery at the oral
      cavity/soft palate than patients that did not (p=0.0001). A good survival rate
      can be obtained for OSCC patients with resectable SPTs/MPTs.

PMID- 17174144
TI  - Expression of heat shock protein 47 in the fibrous tissue adjacent to mouse
      tumour subjected to photodynamic therapy.
AB  - The reaction of normal fibrous tissue adjacent to tumours subjected to
      photodynamic therapy (PDT) was investigated by assessment of the
      immunohistochemical expression of heat shock protein 47 (HSP47) and proliferating
      cell nuclear antigen (PCNA), as well as by immunoblot analysis of procollagen
      type I. PDT was administered to NR-S1 mouse squamous cell carcinoma or normal
      mouse skin. Each of four mice was investigated at several time points after
      receiving PDT. The levels of HSP47 expression were determined by computer
      assisted image analysis. The expression of procollagen type I in the fibrous
      tissue adjacent to the tumours was examined by immunoblot analysis at intervals
      of 24 and 48h after PDT. The expression of HSP47 was first detected 6h post-PDT
      in the tumour-bearing mice, but no such expression was observed in the normal
      mice. It was also revealed that, after PDT, the fibroblast PCNA labeling indices
      at 24, 48, and 72h were significantly higher in both the tumour-bearing and the
      normal mice than in the control animals that did not receive PDT. Furthermore,
      procollagen type I was detected in the fibrous tissue adjacent to the tumours at
      24 and 48h after PDT, but was not detected in the fibrous tissue adjacent to
      tumours of mice that did not receive PDT. Therefore, the present results suggest
      that PDT enhances the synthesis of collagen type I in the fibrous tissue adjacent
      to NR-S1 squamous cell carcinoma in mice, which contributes to the resultant
      encapsulation of such tumours.

PMID- 17174145
TI  - The clinical significance of the positive surgical margin in oral cancer.
AB  - The objective of surgical management of squamous cell carcinoma of the oral
      cavity is adequate resection with a clear margin. This study examines the
      significance of the positive surgical margin. An historical cohort of 425
      patients from the cancer registry of the Province of Manitoba with squamous cell
      carcinoma of the oral cavity treated with surgery +/-radiotherapy was examined. A
      Cox's proportional hazard model was used to examine the independent effect of
      surgical margins on five-year survival. Seventy-two percent of tumors involved
      the tongue and floor of mouth, and 43% of patients presented with Stage III and
      IV disease. The 5-year absolute and disease specific survivals were 62% and 74.5%
      respectively. Survival was related to age >65 years (P=0.0177), T-Stage
      (P=0.0002), and N-Stage (P=0.0465). Patients with clear margins had a survival
      rate of 69% at 5 yrs (median survival >60 mos) compared to 58% with close (median
      survival >60 mos) and 38% with involved margins (median survival 31 mos,
      P=.0000). After controlling for significant prognostic factors, involved surgical
      margins increased the risk of death at 5 years by 90% (HR 1.9, 95% CI 1.2,2.9,
      P=0.0026). The status of the surgical margin is an important predictor of
      outcome. The surgical margin, in contrast to the other prognostic indicators, is
      under the direct control of the surgeon.

PMID- 17174146
TI  - Phosphorus-nitrogen compounds: synthesis and spectral investigations on new spiro
      cyclic phosphazene derivatives.
AB  - The condensation reaction of {N-[(2-hydroxyphenylmethyl)amino]-4,6
      dimethylpyridine} (2), which is a reduction product of 1, with trimer
      N(3)P(3)Cl(6) affords partially a substituted spiro-cyclic phosphazene derivative
      (3). The fully substituted phosphazenes (4 and 5) have also been obtained from
      the reactions of 3 with the excess of pyrrolidine and morpholine. The
      characterizations and spectral investigations of these compounds have been made
      by elemental analyses, FTIR, 1H-, 13C-, 31P NMR, correlation spectroscopy (COSY),
      heteronuclear chemical shift correlation (HETCOR), heteronuclear multiple-bond
      correlation (HMBC) and mass spectroscopy (MS). The salient features of spectral
      data of these compounds have been discussed.

PMID- 17174147
TI  - A participatory assessment of IS integration needs in maternity clinics using
      activity theory.
AB  - The design and development of information systems should focus on a wider context
      than merely one user group or organization. This is particularly the case with
      systems integration. A tentative description of the activity network, information
      needs, and user requirements should be acquired before any major changes are
      planned. Relatively rapid yet participatory methods are needed at this
      preliminary stage. In this article, we claim that activity theory offers a
      suitable framework for this. Subsequently, we present a qualitative study in
      which this approach was used, with focus on the practices of the information
      management within a maternity care activity network. The first aim was to elicit
      the most important integration needs in the existing information systems of
      Finnish maternity clinics. Secondly, we wanted to introduce a participatory
      approach to be utilized by the service-providing organizations themselves, rather
      than software companies or quality consultants. Data were collected in multi
      professional group interviews. The results include information needs and
      communication problems as well as outlines for solutions in the systems
      integration of maternity clinics. Various tools of information management do not
      meet the concrete needs of health care work. Integration is needed on many
      levels, and it has to be adapted to the needs of numerous stakeholders. The
      applied activity-theoretical framework proved useful in describing such a multi
      faceted system of information and its users. More research is needed on its wider
      applicability, particularly in situations where researchers are not active
      participants.

PMID- 17174148
TI  - Small-world network organization of functional connectivity of EEG slow-wave
      activity during sleep.
AB  - OBJECTIVE: To analyze the functional connectivity patterns of the EEG slow-wave
      activity during the different sleep stages and Cyclic Alternating Pattern (CAP)
      conditions, using concepts derived from Graph Theory. METHODS: We evaluated
      spatial patterns of EEG slow-wave synchronization between all possible pairs of
      electrodes (19) placed over the scalp of 10 sleeping healthy young normal
      subjects using two graph theoretical measures: the clustering coefficient (Cp)
      and the characteristic path length (Lp). The measures were obtained during the
      different sleep stages and CAP conditions from the real EEG connectivity networks
      and randomized control (surrogate) networks (Cp-s and Lp-s). RESULTS: Cp and
      Cp/Cp-s increased significantly from wakefulness to sleep while Lp and Lp/Lp-s
      did not show changes. Cp/Cp-s was higher for A1 phases, compared to B phases of
      CAP. CONCLUSIONS: The network organization of the EEG slow-wave synchronization
      during sleep shows features characteristic of small-world networks (high Cp
      combined with low Lp); this type of organization is slightly but significantly
      more evident during the CAP A1 subtypes. SIGNIFICANCE: Our results show
      feasibility of using graph theoretical measures to characterize the complexity of
      brain networks during sleep and might indicate sleep, and the A1 phases of CAP in
      particular, as a period during which slow-wave synchronization shows optimal
      network organization for information processing.

PMID- 17174149
TI  - EEG correlates of subcortical optokinetic nystagmus.
AB  - OBJECTIVE: Our aim was to reveal the changes of concomitant scalp EEG activity
      during subcortical (stare-) optokinetic nystagmus (OKN). METHODS: Stare-OKN of 10
      subjects was evoked and recorded simultaneously with the EEG. Frequency
      distribution of OKN-beats was determined in each subject. Power changes of alpha
      and beta frequency bands of the EEG during OKN stimulation were statistically
      analysed. RESULTS: During continuous subcortical OKN-the EEG alpha power
      decreased significantly while beta power increase was not significant. A
      significant transient alpha power enhancement around the onset of subcortical OKN
      clusters was detected. CONCLUSIONS: We found significant changes in the parieto
      occipital alpha EEG activity during subcortical OKN. The transient alpha
      synchronisation at the beginning of each OKN-cluster is a paradox phenomenon
      which might indicate increased visual attention. SIGNIFICANCE: The present study
      is the first report investigating EEG changes related to subcortical OKN. Our
      findings suggest the involvement of cortical mechanisms in the generation of
      stare-OKN. The results might help in the elucidation of cortico-genicular
      mechanisms of ocular movements under physiological and pathological conditions.

PMID- 17174150
TI  - Effects of GABA(A) and GABA(B) agonists on interhemispheric inhibition in man.
AB  - OBJECTIVE: Animal studies on neurotransmitter systems that mediate
      interhemispheric inhibition (IHI) suggest that, (i) callosal transmission is
      regulated by presynaptic GABA(B) receptors, and (ii) GABA(A)-ergic neurones
      mediate early IHI, whereas GABA(B)-ergic neurones mediate later IHI. In humans
      the mechanism is unclear. Interactions between cortical inhibitory circuits
      suggest a postsynaptic GABA(B)-ergic mechanism. We will here test this
      hypothesis. METHODS: Short-latency IHI (s-IHI) and long-latency IHI (l-IHI) were
      evaluated using the paired pulse paradigm before and under medication with (i) a
      GABA(B)-agonist (baclofen) in 17 subjects, and (ii) a GABA(A)-agonist (midazolam)
      in 10 subjects participating twice. RESULTS: Baclofen did not significantly
      enhance s-IHI. L-IHI between 20 and 50ms was significantly strengthened, and
      obtained also at ISIs between 100 and 200ms. Midazolam had no effect on s-IHI,
      whereas l-IHI was attenuated. CONCLUSIONS: Our results support the hypothesis,
      that l-IHI in humans is mediated by postsynaptic GABA(B) receptors. GABA(A)-ergic
      medication resulted in attenuation of l-IHI. Regarding s-IHI, our results are
      inconclusive and require further investigation. SIGNIFICANCE: This is the first
      human study evaluating the effect of baclofen on IHI, indicating that l-IHI is
      mediated by GABA(B)-ergic neurones. Because interhemispheric interaction is now
      also been used as a therapeutic approach, understanding the underlying
      neurotransmitter systems will be increasingly relevant.

PMID- 17174151
TI  - Clinical syndrome suggestive of heart failure is frequently attributable to non
      cardiac disorders--population-based study.
AB  - AIM: To assess how often the clinical syndrome (CS) of heart failure is
      attributable to alternative, including non-cardiac, explanations. METHODS AND
      RESULTS: Cross-sectional evaluation of 739 community participants aged>or=45
      years. Subjects with >or=2 symptoms or signs (dyspnoea or fatigue, orthopnoea,
      nocturnal paroxysmal dyspnoea, third heart sound, jugular venous distension,
      rales and lower limb oedema) or who were receiving loop diuretics were considered
      to have the clinical syndrome of heart failure. Attributable fractions were
      derived based on adjusted odds ratios and the prevalence of underlying disorders
      among cases. CS was present in 28.0% of women and in 15.2% of men, p<0.001. The
      multivariate-adjusted fraction of CS attributable to female gender was 40.6%, to
      age>or=65 years 28.5%, left ventricular systolic dysfunction, left ventricular
      dilatation or moderate-severe valvular disease 4.9%, diastolic dysfunction or
      atrial fibrillation 13.0%, obesity 22.6%, coronary heart disease 7.2% and chronic
      lung disease 6.9%. When additionally adjusting for depressive symptoms, the
      association with gender and age became much weaker, and 32% of cases were
      attributable to depressive symptoms. Forty-two percent of subjects with CS had
      cardiac abnormalities. CONCLUSION: In less than half of subjects with CS was
      systolic or diastolic heart failure confirmed. Female gender, older age, obesity
      and depressive symptoms accounted for the largest fraction of CS.

PMID- 17174152
TI  - Cognitive impairment in heart failure: a systematic review of the literature.
AB  - BACKGROUND: Heart failure (HF) and cognitive impairment are common medical
      conditions that are becoming increasingly prevalent in the aging Western
      population. They are associated with frequent hospitalisation and increased
      mortality, particularly when they occur simultaneously. Evidence from a number of
      studies suggests that HF is independently associated with impairment in various
      cognitive domains. AIMS: This systematic literature review evaluates the relation
      between cognitive deterioration and heart failure. METHODS: We searched
      electronic databases from 1966 to May 2006 for studies that investigated
      cognitive function in HF patients. Twenty-two controlled studies that met the
      inclusion criteria were selected for analysis. Study characteristics and data on
      global cognitive performance, memory scores, psychomotor speed and depression
      scores were extracted and analysed using the Cochrane Review Manager software.
      RESULTS: Pooled analysis shows diminished neuropsychological performance in HF
      patients, as compared to control subjects. In a pooled sample of 2937 heart
      failure patients and 14,848 control subjects, the odds ratio for cognitive
      impairment was 1.62 (95% confidence interval:1.48-1.79, p<0.0001) among subjects
      with HF. CONCLUSION: This review confirms the relationship between HF and
      cognitive impairment, but it also stresses the need for additional systematic
      neuropsychological data and adequate neuro-imaging from representative
      populations of HF patients.

PMID- 17174153
TI  - No significant difference in cytokine levels in patients with restless legs
      syndrome versus controls - preliminary data.

PMID- 17174154
TI  - Usefulness of biomarkers in population studies: from exposure to susceptibility
      and to prediction of cancer.
AB  - From a review of decades of intensive biomarker research and prospective
      validation studies, it becomes clear that only a limited number of biomarkers can
      be used to provide reliable documentation of excessive exposure to environmental
      mutagenic agents, expression of detrimental biological effects from the exposure
      and increased risk for cancer. These studies also demonstrate that expression of
      each biomarker represents an integrated response to the exposure that is
      influenced by susceptibility factors, and an integral component of the complex
      carcinogenic pathway. A current interest is in the use of phenotypic functional
      assays to improve and complement the assessment of cancer risk. A recommended
      approach includes assays that indicate DNA repair deficiency, i.e. host-cell
      mediated reporter gene and challenge (mutagen-sensitivity) assays. The usefulness
      and limitations in biomarker investigations will be discussed. The review
      emphasizes the need for carefully designed investigations that involve adequate
      sample sizes and a combination of appropriate biomarkers to generate reproducible
      results that can be translated into more reliable cancer risk assessment. The
      assessment can be used to drive the implementation of disease prevention and
      intervention activities. Such an approach is consistent with the current priority
      in translating basic science knowledge into health applications.

PMID- 17174155
TI  - Modification of the Cox-Maze III procedure using bipolar radiofrequency ablation.
AB  - The Cox-Maze III procedure remains the yardstick by which all treatments for
      atrial fibrillation are measured. This procedure is not widely adopted because of
      its perceived technical complexity, invasiveness and longer procedural time.
      Efforts have been made by various investigators to reproduce Dr Cox's results
      using alternative lesion sets and energy sources. Bipolar radiofrequency (BPRF)
      ablation avoids the morbidity of cut-and-sew lesions, reduces procedural time and
      increases the likelihood of transmurality and continuity of lesions created
      compared to unipolar devices. Initial results are encouraging. We present our
      surgical technique and early experience using BPRF modification of the Cox-Maze
      III procedure using the Medtronic Cardioblate BP system.

PMID- 17174156
TI  - Dopamine D3 receptor agonists for protection and repair in Parkinson's disease.
AB  - Parkinson's disease is a severe, age-related neurodegenerative disorder in which
      a loss of substantia nigra-derived dopaminergic pathways to the striatum triggers
      profound motor perturbation, as well as cognitive, sensory and mood deficits.
      Although the dopamine precursor, L-dopa, is effective in the short-term in
      relieving motor dysfunction, it does not stop the progressive disappearance of
      dopaminergic neurons, encouraging interest in alternative therapeutic strategies.
      Dopaminergic agonists, such as pramipexole, appear to have neuroprotective and
      neurorestorative actions based on clinical and, most convincingly, experimental
      work. The role of specific dopaminergic receptor subtypes is an important issue,
      especially with respect to new drug development. Of particular interest, dopamine
      D3 receptors contribute to the beneficial influence of dopaminergic agonists for
      the protection and restoration of dopaminergic pathways in Parkinson's disease.

PMID- 17174157
TI  - Trypanosomes and mammalian sperm: one of a kind?
AB  - Flagellar-mediated motility is an indispensable function for cell types as
      evolutionarily distant as mammalian sperm and kinetoplastid parasites, a large
      group of flagellated protozoa that includes several important human pathogens.
      Despite the obvious importance of flagellar motility, little is known about the
      signalling processes that direct the frequency and wave shape of the flagellar
      beat, or those that provide the motile cell with the necessary environmental cues
      that enable it to aim its movement. Similarly, the energetics of the flagellar
      beat and the problem of a sufficient ATP supply along the entire length of the
      beating flagellum remain to be explored. Recent proteome projects studying the
      flagella of mammalian sperm and kinetoplastid parasites have provided important
      information and have indicated a surprising degree of similarities between the
      flagella of these two cell types.

PMID- 17174158
TI  - Effects of antiepileptic drugs on learning as assessed by a repeated acquisition
      of response sequences task in rats.
AB  - Patients with epilepsy can have impaired cognitive abilities. Antiepileptic drugs
      (AEDs) may contribute to the cognitive deficits observed in patients with
      epilepsy, and have been shown to induce cognitive impairments in healthy
      individuals. However, there are few systematic data on the effects of AEDs on
      specific cognitive domains. We have previously demonstrated that a number of AEDs
      can impair working memory and attention. The purpose of the present study was to
      evaluate the effects of AEDs on learning as measured by a repeated acquisition of
      response sequences task in nonepileptic rats. The GABA-related AEDs phenobarbital
      and chlordiazepoxide significantly disrupted performance by shifting the learning
      curve to the right and increasing errors, whereas tiagabine and valproate did
      not. The sodium channel blockers carbamazepine and phenytoin suppressed
      responding at higher doses, whereas lamotrigine shifted the learning curve to the
      right and increased errors, and topiramate was without significant effect.
      Levetiracetam also shifted the learning curve to the right and increased errors.
      The disruptions produced by triazolam, chlordiazepoxide, lamotrigine, and
      levetiracetam were qualitatively similar to the effects of the muscarinic
      cholinergic receptor antagonist scopolamine. The present results indicate that
      AEDs can impair learning, but there are differences among AEDs in the magnitude
      of the disruption in nonepileptic rats, with drugs that enhance GABA receptor
      function and some that block sodium channels producing the most consistent
      impairment of learning.

PMID- 17174159
TI  - Small airway changes in healthy and ovalbumin-treated mice during quasi-static
      lung inflation.
AB  - Previously, we developed a synchrotron radiation CT system to evaluate the
      morphometric changes (length and diameter, D) and small airway compliance
      (sC(aw)) of euthanized mice under quasi-static inflation [Sera, T., Uesugi, K.,
      Yagi, N., 2005. Localized morphometric deformations of small airways and alveoli
      in intact mouse lungs under quasi-static inflation. Respir. Physiol. Neurobiol.
      147, 51-63). Using this system, this study compared normal and asthmatic small
      airways. Ovalbumin-treated mice were used as an asthma model. Compared with the
      values at functional residual capacity, D of normal and asthmatic small airways
      (D<200microm) increased by 48% and 36% at the end of tidal inspiration. For
      larger airways (D>500microm), the increases were 23% and 20%, respectively. The
      ratio of the sC(aw) of asthmatic small airways to that of healthy small airways
      was 0.57, and the ratio was 0.70 for larger airways. The morphometric changes and
      sC(aw) in asthma model mice were significantly lower than those of healthy mice.
      The differences in sC(aw) between healthy and asthma model mice were greater for
      smaller airways.

PMID- 17174160
TI  - Targeted quantitative analysis of fatty acids in atherosclerotic plaques by high
      sensitivity liquid chromatography/tandem mass spectrometry.
AB  - The quantitative analysis of fatty acid composition in atherosclerotic plaques
      provides a way to monitor the underlying etiology of atherosclerosis. Previously,
      the method of choice for analyzing fatty acids in biological samples was gas
      chromatography/mass spectrometry (GC/MS); however, recent developments in
      electrospray ionization (ESI)/liquid chromatography (LC)/tandem mass spectrometry
      have made it a superior alternative. Previous research has largely focused on
      global analyses of intact lipids rather than more targeted analysis of the fatty
      acids themselves. We have now developed a targeted, stable isotope dilution LC
      electrospray ionization/multiple reaction monitoring/MS method for the
      quantitative analysis of 10 fatty acids (myristic, palmitic, stearic, oleic,
      linoleic, alpha-linolenic, gamma-linolenic, arachidonic, eicosapentaenoic, and
      docosahexaenoic acids) using their trimethylaminoethyl ester (TMAE) derivatives
      to improve sensitivity. The method was validated, had a detection limit in the
      fmol range, and was used in the analysis of fatty acids in atherosclerotic
      plaques from carotid arteries.

PMID- 17174161
TI  - Prion infection-impaired functional blocks identified by proteomics enlighten the
      targets and the curing pathways of an anti-prion drug.
AB  - Prion-induced neurodegeneration results from multiple cellular alterations among
      which the accumulation of a modified form of the host protein PrP is but a
      hallmark. Drug treatments need understanding of underlying mechanisms. Proteomics
      allows getting a comprehensive view of perturbations leading to neuronal death.
      Heparan sulfate mimetics has proved to be efficient to clear scrapie protein in
      cultured cells and in animals. To investigate the mechanisms of drug attack,
      protein profiles of the neuronal cell line GT1 and its chronically Chandler
      strain infected counterpart were compared, either in steady state cultures or
      after a 4-day drug treatment. Differentially expressed proteins were associated
      into functional blocks relevant to neurodegenerative diseases. Protein structure
      repair and modification, proteolysis, cell shape and energy/oxidation players
      were affected by infection, in agreement with prion biology. Unexpectedly, novel
      affected blocks related to translation, nucleus structure and DNA replication
      were unravelled displaying commonalities with proliferative processes. The drug
      had a double action in infected cells by reversing protein levels back to normal
      in some blocks and by heightening survival functions in others. This study
      emphasizes the interest of a proteomic approach to unravel novel networks
      involved in prion infection and curing.

PMID- 17174162
TI  - The presence of a common channel and associated pancreaticobiliary diseases: a
      prospective ERCP study.
AB  - BACKGROUND: There are few endoscopic retrograde cholangiographic studies dealing
      with the relationship between the presence of a common channel and associated
      pancreaticobiliary diseases. AIMS: To endoscopically determine the incidence of
      common channels and assess whether the anatomy of the pancreaticobiliary ductal
      drainage into the duodenum has any bearing on pancreaticobiliary diseases.
      PATIENTS AND METHODS: We prospectively examined a common channel formation in 354
      endoscopic retrograde cholangiographic cases. Cases with a common channel were
      divided into three groups: pancreaticobiliary maljunction, high confluence of
      pancreaticobiliary ducts with a common channel > or =6 mm in which the
      communication was occluded with the sphincter contraction, and common channel <
      or =5 mm in length. RESULTS: A common channel was observed in 131 cases (37.0%)
      including 11 with pancreaticobiliary maljunction and 13 with high confluence of
      pancreaticobiliary ducts. In cases with a common channel, the incidences of
      associated gallbladder carcinoma and acute pancreatitis were both 11.5%, which
      were significantly higher than 1.8% and 4.9% seen in cases without a common
      channel. In pancreaticobiliary maljunction cases, incidence of associated
      gallbladder carcinoma was 72.7%. CONCLUSION: The presence of an obvious common
      channel was observed in 37.0%. A close relationship is suggested between the
      presence of a common channel and development of gallbladder carcinoma and acute
      pancreatitis.

PMID- 17174163
TI  - Diagnosing coeliac disease: is the videocapsule a suitable tool?

PMID- 17174164
TI  - An exceptional complex chromosomal rearrangement (CCR) with eight breakpoints
      involving four chromosomes (1;3;9;14) in an azoospermic male with normal
      phenotype.
AB  - A 27-year-old man was referred for chromosome analysis due to infertility caused
      by azoospermia. Chromosome analysis by conventional karyotyping, multicolour FISH
      (M-FISH) and multicolour banding (MCB) analysis revealed an apparently balanced
      translocation between chromosomes 1, 3, 9 and 14 as well as an additional
      inverted insertion of 3q material with a total of eight breakpoints. Due to the
      diversity of theoretically unbalanced products of meiotic recombination in this
      exceptional complex chromosomal rearrangement a successful result of assisted
      reproduction seems unlikely.

PMID- 17174165
TI  - It's beyond water: stories of women's experience of using water for labour and
      birth.
AB  - PURPOSE: This study aimed to give 'voice' to women's experiences of using water
      for labour and birth. PARTICIPANTS: Five women from a large urban region in New
      Zealand, who used water for labour and birth, at home and in hospital. METHODS:
      The study employed an interpretive design using audio-taped conversations as the
      method of data collection and a thematic analysis of the women's stories.
      FINDINGS: Data analysis produced two core categories; 'Getting to the water'
      which revealed the impact of preparing for and anticipating the water; and
      'Getting into the water' which provided a sanctuary and a release from pain.
      CONCLUSION: The all-encompassing warmth associated with being enveloped in warm
      water cradled, supported, relaxed, comforted, soothed, sheltered and protected
      the women; it created a barrier and offered a sense of privacy. Water can be used
      in any form, even the act of thinking about, preparing for and anticipating the
      water opened possibilities for these women. The women used water to reduce their
      fear of pain and of childbirth itself; to cope with pain, not necessarily to
      remove or diminish pain; and to maintain control over the process of birth. The
      women indicated that it was not necessary to actually give birth in the water to
      achieve these benefits. Listening to the stories of women provides us with
      insights into what is important to them. Women's knowledge contributes an
      important part of the evidence on which we base our practice.

PMID- 17174166
TI  - The antioxidant effect of estrogen and Selective Estrogen Receptor Modulators in
      the inhibition of osteocyte apoptosis in vitro.
AB  - Withdrawal of estrogen represents the primary factor determining post menopausal
      bone loss and has been associated with negative indicators of bone quality
      including the apoptotic death of osteocytes in vivo. While hormone replacement
      therapy in the form of Estrogen or Selective Estrogen Receptor Modulators (SERMs)
      demonstrates clear estrogen receptor (ER)-mediated benefits to bone mass, less is
      known regarding the mechanism of action of these compounds in the maintenance of
      bone cell populations. We have investigated the potential antioxidant effects of
      estrogen, estrogen derivatives and the SERMs Raloxifene and LY117018 in the
      prevention of oxidative stress induced apoptosis in the osteocyte like cell line
      MLO-Y4. Treatment of MLO-Y4 with 0.3 mM H(2)O(2) induced apoptosis that was
      significantly inhibited (p< or =0.002) when the cells were pre-treated for 1 h
      with either 17beta-estradiol, Raloxifene or LY117018 (10 nM). The stereoisomer
      17alpha-estradiol also prevented H(2)O(2) induced apoptosis in MLO-Y4.
      Importantly, pre-treatment of ER-negative HEK293 cells with either 1 microM, 100
      nM or 10 nM 17beta-estradiol, Raloxifene or LY117018 significantly inhibited
      H(2)O(2) induced apoptosis in these cells (p< or =4.2x10(-5)) indicating an
      estrogen receptor-independent effect of these compounds. Comparisons of 17beta
      estradiol and similar molecules containing the putative free radical scavenger C3
      OH moiety on the steroid A-ring (17alpha-estradiol, 17alpha-ethinylestradiol; 10
      nM) with structurally related molecules lacking the C3-OH grouping (Mestranol and
      Quinestrol; 10 nM) demonstrated that only compounds containing the C3-OH moiety
      showed anti-apoptotic behavior in these studies (p< or =0.0033). Similarly the
      identification of the presence of reactive oxygen species (ROS) in cells as
      evidenced by the free radical indicator 2'7'-dichlorodihydrofluorescein diacetate
      demonstrated that 17beta-estradiol, SERMs and related molecules with C3-OH moiety
      were capable of blocking ROS generated in cells by H(2)O(2) (p< or =0.002) while
      Mestranol and Quinestrol showed no such blockade. It is possible that the loss of
      osteocytes during estrogen insufficiency may occur through a failure to suppress
      the activity of naturally occurring or disease associated oxidant molecules.
      These data suggest that the osteocyte protective effects of estrogen and SERMs
      may operate through a common receptor-independent mechanism which may be related
      to the antioxidant activity of these molecules.

PMID- 17174167
TI  - Letter from the editor: fighting germs in the workplace.

PMID- 17174169
TI  - Case of the season: disseminated nocardiosis.

PMID- 17174170
TI  - Infection in the intensive care unit: a clinician's view of the role of imaging.

PMID- 17174171
TI  - Infectious complications of solid organ transplantation.

PMID- 17174172
TI  - Thoracic infections in human immunodeficiency virus/acquired immune deficiency
      syndrome.

PMID- 17174173
TI  - Imaging manifestations of tropical parasitic infections.

PMID- 17174174
TI  - Radiology of biological weapons--old and the new?

PMID- 17174176
TI  - Emerging therapies for the management of decompensated heart failure: from bench
      to bedside.
AB  - While pharmaceutical innovation has been highly successful in reducing mortality
      in chronic heart failure, this has not been matched by similar success in
      decompensated heart failure syndromes. Despite outstanding issues over
      definitions and end points, we argue in this paper that an unprecedented wealth
      of pharmacologic innovation may soon transform the management of these
      challenging patients. Agents that target contractility, such as cardiac myosin
      activators and novel adenosine triphosphate-dependent transmembrane sodium
      potassium pump inhibitors, provide inotropic support without arrhythmogenic
      increases in cytosolic calcium or side effects of more traditional agents.
      Adenosine receptor blockade may improve glomerular filtration and diuresis by
      exerting a direct beneficial effect on glomerular blood flow while vasopressin
      antagonists promote free water excretion without compromising renal function and
      may simultaneously inhibit myocardial remodeling. Urodilatin, the renally
      synthesized isoform of atrial natriuretic peptide, may improve pulmonary
      congestion via vasodilation and enhanced diuresis. Finally, metabolic modulators
      such as perhexiline may optimize myocardial energy utilization by shifting
      adenosine triphosphate production from free fatty acids to glucose, a unique and
      conceptually appealing approach to the management of heart failure. These
      advances allow optimism not only for the advancement of our understanding and
      management of decompensated heart failure syndromes but for the translational
      research effort in heart failure biology in general.

PMID- 17174177
TI  - Noninvasive cardiac imaging in patients with hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and
      the most common cause of cardiac death in young athletes in the U.S. Noninvasive
      imaging plays an important role in detecting the disease, understanding its
      pathophysiology, and selecting as well as guiding appropriate therapy. In this
      review, we discuss the existing methodology with emphasis on current and emerging
      clinical applications in patients with HCM.

PMID- 17174178
TI  - Randomized double-blind comparison of sirolimus-eluting stent versus bare-metal
      stent implantation in diseased saphenous vein grafts: six-month angiographic,
      intravascular ultrasound, and clinical follow-up of the RRISC Trial.
AB  - OBJECTIVES: We sought to compare, in a randomized fashion, sirolimus-eluting
      stents (SES) versus bare-metal stents (BMS) in saphenous vein grafts (SVGs).
      BACKGROUND: Sirolimus-eluting stents reduce restenosis and repeated
      revascularization in native coronary arteries compared with BMS. However,
      randomized data in SVG are absent. METHODS: Patients with SVG lesions were
      randomized to SES or BMS. All were scheduled to undergo 6-month coronary
      angiography. The primary end point was 6-month angiographic in-stent late lumen
      loss. Secondary end points included binary angiographic restenosis, neointimal
      volume by intravascular ultrasound and major adverse clinical events (death,
      myocardial infarction, target lesion, and vessel revascularization). RESULTS: A
      total of 75 patients with 96 lesions localized in 80 diseased SVGs were included:
      38 patients received 60 SES for 47 lesions, whereas 37 patients received 54 BMS
      for 49 lesions. In-stent late loss was significantly reduced in SES (0.38 +/-
      0.51 mm vs. 0.79 +/- 0.66 mm in BMS, p = 0.001). Binary in-stent and in-segment
      restenosis were reduced, 11.3% versus 30.6% (relative risk [RR] 0.37; 95%
      confidence interval [CI] 0.15 to 0.97, p = 0.024) and 13.6% versus 32.6% (RR
      0.42; 95% CI 0.18 to 0.97, p = 0.031), respectively. Median neointimal volume was
      1 mm(3) (interquartile range 0 to 13) in SES versus 24 (interquartile range 8 to
      34) in BMS (p < 0.001). Target lesion and vessel revascularization rates were
      significantly reduced, 5.3% versus 21.6% (RR 0.24; 95% CI 0.05 to 1.0, p = 0.047)
      and 5.3% versus 27% (RR 0.19; 95% CI 0.05 to 0.83, p = 0.012), respectively.
      Death and myocardial infarction rates were not different. CONCLUSIONS: Sirolimus
      eluting stents significantly reduce late loss in SVG as opposed to BMS. This is
      associated with a reduction in restenosis rate and repeated target lesion and
      vessel revascularization procedures. (The RRISC Study;
      http://clinicaltrials.gov/ct/show; NCT00263263).

PMID- 17174179
TI  - Two-year follow-up of the quantitative angiographic and volumetric intravascular
      ultrasound analysis after nonpolymeric paclitaxel-eluting stent implantation:
      late "catch-up" phenomenon from ASPECT Study.
AB  - OBJECTIVES: This study used serial angiographic and intravascular ultrasound
      (IVUS) analysis to evaluate the long-term efficacy of a nonpolymeric, paclitaxel
      eluting stent coating on intimal hyperplasia (IH) 2 years after implantation.
      BACKGROUND: Long-term efficacy of patients treated with nonpolymeric paclitaxel
      eluting stents beyond 1 year has not been well determined. METHODS: Patients were
      randomized to placebo or 1 of 2 doses of paclitaxel (low dose, 1.28 microg/mm2;
      high dose, 3.10 microg/mm2). Complete after-procedure, 6-month, and 2-year
      angiographic and IVUS data were available in 53 patients (17, 17, and 19
      patients, respectively). RESULTS: Baseline characteristics were similar among the
      3 groups. Although 6-month minimal luminal diameter (MLD) was significantly
      smaller in placebo compared with paclitaxel-eluting stent patients (1.9 +/- 0.6
      mm in placebo, 2.5 +/- 0.6 mm in low-dose, and 2.6 +/- 0.5 mm in high-dose
      patients, p = 0.004), the MLDs at 2 years were similar (2.3 +/- 0.6 mm, 2.3 +/-
      0.7 mm, and 2.0 +/- 0.8 mm, respectively, p = 0.4). Despite a stepwise reduction
      in IH accumulation at 6 months (23 +/- 18 mm3 in placebo, 14 +/- 11 mm3 in low
      dose, and 10 +/- 12 mm3 in high-dose, p = 0.017), the increase of IH volume from
      6 months to 2 years was significantly greater in the high-dose patients (13 +/-
      14 mm3 in high-dose vs. 4 +/- 7 mm3 in low-dose patients, p = 0.074; and vs. 1 +/
      13 mm3 in placebo, p = 0.019). Late target lesion revascularization (beyond 1
      year) was performed in 2 high-dose patients. CONCLUSIONS: Despite the suppression
      of IH after non-polymeric paclitaxel-eluting stents compared with bare-metal
      stents at 6 months, a "late catch-up" IH growth was found in the high-dose
      patients at 2-year follow-up.

PMID- 17174180
TI  - Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with
      native coronary artery disease: a randomized controlled trial.
AB  - OBJECTIVES: This trial examined the relative clinical efficacy, angiographic
      outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a
      phosphorylcholine polymer versus sirolimus-eluting stents (SES). BACKGROUND:
      Whether a cobalt-based alloy stent coated with the novel antiproliferative agent,
      zotarolimus, and a phosphorylcholine polymer may provide similar angiographic and
      clinical benefit compared with SES is undetermined. METHODS: A prospective,
      multicenter, 3:1 randomized trial was conducted to evaluate the safety and
      efficacy of ZES (n = 323) relative to SES (n = 113) in 436 patients undergoing
      elective percutaneous revascularization of de novo native coronary lesions with
      reference vessel diameters between 2.5 mm and 3.5 mm and lesion length > or =14
      mm and < or =27 mm. The primary end point was 8-month angiographic in-segment
      late lumen loss. RESULTS: Angiographic in-segment late lumen loss was
      significantly higher among patients treated with ZES compared with SES (0.34 +/-
      0.44 mm vs. 0.13 +/- 0.32 mm, respectively; p < 0.001). In-hospital major adverse
      cardiac events were significantly lower among patients treated with ZES (0.6% vs.
      3.5%, p = 0.04). In-segment binary angiographic restenosis was also higher in the
      ZES cohort (11.7% vs. 4.3%, p = 0.04). Total (clinically and non-clinically
      driven) target lesion revascularization rates at 9 months were 9.8% and 3.5% for
      the ZES and SES groups, respectively (p = 0.04). However, neither clinically
      driven target lesion revascularization (6.3% zotarolimus vs. 3.5% sirolimus, p =
      0.34) nor target vessel failure (12.0% zotarolimus vs. 11.5% sirolimus, p = 1.0)
      differed significantly. CONCLUSIONS: Compared with SES, treatment with a
      phosphorylcholine polymer-based ZES is associated with significantly higher late
      lumen loss and binary restenosis at 8-month angiographic follow-up. (The Endeavor
      III CR; http://clinicaltrials.gov/ct/show/NCT00265668?order=1?).

PMID- 17174181
TI  - A multinational study to establish the value of early adenosine technetium-99m
      sestamibi myocardial perfusion imaging in identifying a low-risk group for early
      hospital discharge after acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to determine whether gated adenosine Tc
      99m sestamibi single-photon emission computed tomography (ADSPECT) could
      accurately define risk and thereby guide therapeutic decision making in stable
      survivors of acute myocardial infarction (AMI). BACKGROUND: Controversy continues
      as to the role of noninvasive stress imaging in stratifying risk early after AMI.
      METHODS: The INSPIRE (Adenosine Sestamibi Post-Infarction Evaluation) trial is a
      prospective multicenter trial which enrolled 728 clinically stable survivors of
      AMI who had gated ADSPECT within 10 days of hospital admission and subsequent 1
      year follow-up. Event rates were assessed within prospectively defined INSPIRE
      risk groups based on the adenosine-induced left ventricular perfusion defect
      size, extent of ischemia, and ejection fraction. RESULTS: Total cardiac
      events/death and reinfarction significantly increased within each INSPIRE risk
      group from low (5.4%, 1.8%), to intermediate (14%, 9.2%), to high (18.6%, 11.6%)
      (p < 0.01). Event rates at 1 year were lowest in patients with the smallest
      perfusion defects but progressively increased when defect size exceeded 20% (p <
      0.0001). The perfusion results significantly improved risk stratification beyond
      that provided by clinical and ejection fraction variables. The low-risk INSPIRE
      group, comprising one-third of all enrolled patients, had a shorter hospital stay
      with lower associated costs compared with the higher-risk groups (p < 0.001).
      CONCLUSIONS: Gated ADSPECT performed early after AMI can accurately identify a
      sizeable low-risk group who have a <2% death and reinfarction rate at 1 year.
      Identifying these low-risk patients for early hospital discharge may improve
      utilization of health care resources at considerable cost savings.

PMID- 17174183
TI  - Noninvasive risk stratification after myocardial infarction: new evidence, new
      questions.

PMID- 17174182
TI  - An initial strategy of intensive medical therapy is comparable to that of
      coronary revascularization for suppression of scintigraphic ischemia in high-risk
      but stable survivors of acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to determine the relative benefit of
      intensive medical therapy compared with coronary revascularization for
      suppressing scintigraphic ischemia. BACKGROUND: Although medical therapies can
      reduce myocardial ischemia and improve patient survival after acute myocardial
      infarction, the relative benefit of medical therapy versus coronary
      revascularization for reducing ischemia is unknown. METHODS: A prospective
      randomized trial in 205 stable survivors of acute myocardial infarction was made
      to define the relative efficacy of an intensive medical therapy strategy versus
      coronary revascularization for suppressing scintigraphic ischemia as assessed by
      serial gated adenosine Tc-99m sestamibi myocardial perfusion tomography. All
      patients at baseline had large total (> or =20%) and ischemic (> or =10%)
      adenosine-induced left ventricular perfusion defects and an ejection fraction >
      or =35%. Imaging was performed during 1 to 10 days of hospital admission and
      repeated in an identical fashion after optimization of therapy. Patients
      randomized to either strategy had similar baseline demographic and scintigraphic
      characteristics. RESULTS: Both intensive medical therapy and coronary
      revascularization induced significant but comparable reductions in total (-16.2
      +/- 10% vs. -17.8 +/- 12%; p = NS) and ischemic (-15 +/- 9% vs. -16.2 +/- 9%; p =
      NS) perfusion defect sizes. Likewise, a similar percentage of patients randomized
      to medical therapy versus coronary revascularization had suppression of adenosine
      induced ischemia (80% vs. 81%; p = NS). CONCLUSIONS: Sequential adenosine
      sestamibi myocardial perfusion tomography can effectively monitor changes in
      scintigraphic ischemia after anti-ischemic medical or coronary revascularization
      therapy. A strategy of intensive medical therapy is comparable to coronary
      revascularization for suppressing ischemia in stable patients after acute
      infarction who have preserved LV function.

PMID- 17174184
TI  - Apolipoprotein E genotype and circulating interleukin-10 levels in patients with
      stable and unstable coronary artery disease.
AB  - OBJECTIVES: This study was designed to assess the relation between apolipoprotein
      E (apoE) genotype and serum interleukin (IL)-10 levels in patients with acute
      coronary syndrome (ACS) and chronic stable angina (CSA). BACKGROUND: Genetic
      variations in the apoE gene affect the risk for coronary artery disease (i.e.,
      carriers of the e4 allele have an increased risk). Increased levels of C-reactive
      protein (CRP), an inflammatory marker, correlate with an increased risk of acute
      coronary events, whereas increased IL-10 concentrations have an atheroprotective
      role. Studies have reported a negative association between the apoE e4 allele and
      CRP levels. METHODS: Apolipoprotein E genotypes were assessed in 166 consecutive
      ACS patients (119 men, mean age 68 years, interquartile range [IQR] 60 to 74
      years) and 70 CSA patients (54 men, mean age 65 years, IQR 62 to 68 years). Serum
      IL-10 and CRP were assessed at study entry. RESULTS: Analysis of covariance
      showed that genetic variation in the apoE gene locus significantly influences
      serum IL-10 levels in both ACS (p = 0.009) and CSA patients (p = 0.013). Among
      ACS patients, IL-10 levels were lower in E3/E4 carriers compared with E3/E3
      carriers (p = 0.01) and marginally lower compared with E2/E3 carriers (p =
      0.065). Among CSA patients, IL-10 levels were lower in E3/E4 carriers compared
      with E2/E3 carriers (p = 0.004) and marginally lower compared with E3/E3 carriers
      (p = 0.086). CONCLUSIONS: The IL-10 concentrations differ in ACS and in CSA
      patients with different apoE genotypes. The e4 allele was associated with a trend
      toward lower IL-10 serum levels. Our results may provide an explanation of
      findings in previous studies that cardiovascular risk is higher in e4 carriers
      despite the presence of low CRP levels.

PMID- 17174185
TI  - Ischemia-modified albumin in relation to exercise stress testing.
AB  - OBJECTIVES: We examined whether ischemia-modified albumin (IMA) plasma levels
      change during exercise stress testing (EST) in patients with known coronary
      artery disease and whether the induced changes differ between positive and
      negative exercise tests. BACKGROUND: Ischemia modified albumin is considered a
      marker of myocardial ischemia and increases after coronary angioplasty and in
      acute coronary syndromes. METHODS: We studied 40 consecutive patients with
      established coronary artery disease who underwent EST. Venous samples, for IMA
      measurement, were collected before the stress test (baseline), at peak exercise,
      and 60 min after the completion of the exercise test. RESULTS: There was
      significant difference in the IMA values at the 3 prespecified time points (p =
      0.012), whereas there was no interaction between the IMA changes and the result
      of the stress test, whether positive or negative (p for the interaction term =
      0.94). Baseline, peak EST, and post-EST IMA levels were similar in patients with
      positive and negative exercise tests (p = 0.61). The IMA significantly decreased
      at peak exercise compared with baseline values in positive (p < 0.0001) and in
      negative EST (p = 0.012). Moreover, IMA concentration increased 60 min after EST
      compared with peak-EST values in positive (p < 0.0001) and in negative tests (p =
      0.003), returning to pre-EST levels in both groups. CONCLUSIONS: The IMA plasma
      levels change significantly during exercise testing in patients with coronary
      artery disease, but there is no difference between positive and negative stress
      tests; this possibly implies that the observed changes do not reflect myocardial
      ischemia.

PMID- 17174187
TI  - Anemia in heart failure time to rethink its etiology and treatment?

PMID- 17174186
TI  - Etiology of anemia in patients with advanced heart failure.
AB  - OBJECTIVES: We prospectively investigated the causes of anemia in patients with
      advanced congestive heart failure (CHF). BACKGROUND: Anemia is common in patients
      with advanced CHF, and its etiology is generally considered to be multifactorial.
      However, despite its importance, precise information is lacking regarding the
      prevalence of putative etiologic factors. METHODS: Patients who were hospitalized
      for decompensated advanced CHF and who were stabilized after their initial
      treatment underwent evaluation of "clinically significant" anemia, defined as a
      hemoglobin content <12 g/dl for men and <11.5 g/dl for women. Patients with a
      serum creatinine concentration >3 mg/dl or patients with concurrent diseases that
      are known to cause anemia were not included. The initial evaluation included
      measurements of vitamin B(12), folic acid, thyroid-stimulating hormone,
      erythropoietin, lactate dehydrogenase, Coombs test, multiple fecal occult tests,
      and bone marrow aspiration. Patients without diagnosis by these methods underwent
      red cell mass measurement with (51)Cr assay. RESULTS: The mean age of the 37
      patients was 57.9 +/- 10.9 years and mean left ventricular ejection fraction 22.5
      +/- 5.9%. Iron deficiency anemia was confirmed by bone marrow aspiration in 27
      patients (73%), 2 patients (5.4%) had dilutional anemia, and 1 patient (2.7%) had
      drug-induced anemia. No specific cause was identified in 7 patients (18.9%) who
      were considered to have "anemia of chronic disease." Serum ferritin for the iron
      deficient patients was not a reliable marker of iron deficiency in this
      population. CONCLUSIONS: In this group of patients, iron deficiency was the most
      common cause of anemia. The iron status of patients with end-stage chronic CHF
      should be thoroughly evaluated and corrected before considering other therapeutic
      interventions.

PMID- 17174188
TI  - Pulmonary vein total occlusion following catheter ablation for atrial
      fibrillation: clinical implications after long-term follow-up.
AB  - OBJECTIVES: We present the clinical course and management outcomes of patients
      with total pulmonary vein occlusion (PVO). BACKGROUND: Pulmonary vein occlusion
      is a rare complication that can develop after radiofrequency catheter ablation
      (RFA) of atrial fibrillation (AF). The long term follow-up data of patients
      diagnosed with PVO are minimal. METHODS: Data from 18 patients with complete
      occlusion of at least one pulmonary vein (PV) were prospectively collected. All
      patients underwent RFA for AF using different strategies between September 1999
      and May 2004. Pulmonary vein occlusion was diagnosed using computed tomography
      (CT) and later confirmed by angiography when intervention was warranted. Lung
      perfusion scans were performed on all patients before and after intervention. The
      percent stenoses of the veins draining each independent lung were added together
      to yield an average cumulative stenosis of the vascular cross-sectional area
      draining the affected lung (cumulative stenosis index [CSI]). RESULTS: The
      patients' symptoms had a positive correlation with the CSI (r = 0.843, p < 0.05)
      and a negative one with the lung perfusion (r = -0.667, p < 0.05). A CSI > or
      =75% correlated well with low lung perfusion (<25%; r = -0.854, p < 0.01).
      Patients with a CSI > or =75% appeared to improve mostly when early (r = -0.497)
      and repeat dilation/stenting (r = 0.0765) were performed. CONCLUSIONS: Patients
      with single PVO are mostly asymptomatic and should undergo routine imaging. On
      the other hand, patients with concomitant ipsilateral PV stenosis/PVO and a CSI >
      or =75% require early and, when necessary, repeated pulmonary interventions for
      restoration of pulmonary flow and prevention of associated lung disease.

PMID- 17174190
TI  - Relationship between noninvasive coronary angiography with multi-slice computed
      tomography and myocardial perfusion imaging.
AB  - OBJECTIVES: The aim of this study was to perform a head-to-head comparison
      between multi-slice computed tomography (MSCT) and myocardial perfusion imaging
      (MPI) in patients with an intermediate likelihood of coronary artery disease
      (CAD) and to compare non-invasive findings to invasive coronary angiography.
      BACKGROUND: Multi-slice computed tomography detects atherosclerosis, whereas MPI
      detects ischemia; how these 2 techniques compare in patients with an intermediate
      likelihood of CAD is unknown. METHODS: A total of 114 patients, mainly with
      intermediate likelihood of CAD, underwent both MSCT and MPI. The MSCT studies
      were classified as having no CAD, nonobstructive (<50% luminal narrowing) CAD, or
      obstructive CAD. Myocardial perfusion imaging examinations were classified as
      showing normal or abnormal (reversible and/or fixed defects). In a subset of 58
      patients, invasive coronary angiography was performed. RESULTS: On the basis of
      the MSCT data, 41 patients (36%) were classified as having no CAD, of whom 90%
      had normal MPI. A total of 33 patients (29%) showed non-obstructive CAD, whereas
      at least 1 significant (> or =50% luminal narrowing) lesion was observed in the
      remaining 40 patients (35%). Only 45% of patients with an abnormal MSCT had
      abnormal MPI; even in patients with obstructive CAD on MSCT, 50% still had a
      normal MPI. In the subset of patients undergoing invasive angiography, the
      agreement with MSCT was excellent (90%). CONCLUSIONS: Myocardial perfusion
      imaging and MSCT provide different and complementary information on CAD, namely,
      detection of atherosclerosis versus detection of ischemia. As compared to
      invasive angiography, MSCT has a high accuracy for detecting CAD in patients with
      an intermediate likelihood of CAD.

PMID- 17174189
TI  - Role of Purkinje fibers in post-infarction ventricular tachycardia.
AB  - OBJECTIVES: The objective of this study was to assess the role of Purkinje fibers
      in monomorphic, post-infarction ventricular tachycardia (VT). BACKGROUND:
      Ventricular fibrillation and polymorphic VT in the setting of acute myocardial
      infarction (MI) may be triggered by ectopy arising from Purkinje fibers. METHODS:
      From among a group of 81 consecutive patients with post-infarction monomorphic VT
      referred for catheter ablation, 9 patients were identified in whom the clinical
      VT had a QRS duration < or =145 ms. Mapping was performed focusing on areas with
      Purkinje potentials. RESULTS: A total of 11 VTs with a QRS duration < or =145 ms
      were induced and mapped in the 9 patients; 9 of the 11 VTs had a right bundle
      branch block/left-axis morphology that mimicked left posterior fascicular VT. The
      mean VT cycle length was 402 +/- 82 ms. Eight of 9 patients had a history of
      inferior MI involving the left ventricular septum. One patient had an anterior
      wall MI with septal involvement. Mapping during VT demonstrated re-entry
      involving the inferior left ventricular wall. In each of the VTs, a Purkinje
      potential was present at the exit site of the VT re-entry circuit. Single
      radiofrequency catheter ablation lesions were successful in eliminating these VTs
      in all patients. CONCLUSIONS: The Purkinje system may be part of the re-entry
      circuit in patients with post-infarction monomorphic VT, resulting in a type of
      VT with a relatively narrow QRS complex that mimics fascicular VT.

PMID- 17174191
TI  - Myocardial perfusion imaging and multidetector computed tomographic coronary
      angiography: appropriate for all patients with suspected coronary artery disease?

PMID- 17174192
TI  - Structural abnormalities of the inferoseptal left ventricular wall detected by
      cardiac magnetic resonance imaging in carriers of hypertrophic cardiomyopathy
      mutations.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether structural left
      ventricular (LV) abnormalities can be observed in hypertrophic cardiomyopathy
      (HCM) mutation carriers who have not yet developed echocardiographic signs of
      hypertrophy by using cardiac magnetic resonance imaging (CMR). BACKGROUND:
      Hypertrophic cardiomyopathy is caused by mutations of genes encoding for
      sarcomeric proteins. Myocyte disarray and interstitial fibrosis precede the
      development of regional hypertrophy in HCM mutation carriers (carriers). No
      macroscopic LV structural abnormalities have been observed in carriers without LV
      hypertrophy. METHODS: A CMR, echocardiogram, and electrocardiogram (ECG) were
      performed in 16 carriers. Delayed contrast enhancement imaging was used with CMR
      to detect fibrosis. In 16 age- and gender-matched control subjects, CMR and ECG
      were performed and an echocardiogram was made when structural abnormalities were
      detected with CMR. All carriers had an LV wall thickness <13 mm in the year
      before the study, measured by echocardiography. RESULTS: In 13 carriers (81%),
      crypts were discerned with CMR in the basal and mid inferoseptal LV wall, not
      detected by routine echocardiography and not observed in healthy volunteers. In 4
      of the crypt-positive carriers, both the echocardiogram and ECG were normal. Two
      HCM carriers revealed regional hypertrophy of the inferoseptum not detected by
      echocardiography, and in both carriers, focal fibrosis was present. CONCLUSIONS:
      In carriers who have not yet developed frank hypertrophy, crypts can be detected
      with CMR in the inferoseptal LV wall, even when echocardiography and ECG are
      normal. The crypts might represent one of the early pathological alterations of
      myocardium in carriers that ultimately progress into manifest HCM.

PMID- 17174193
TI  - Head-to-head comparison of two- and three-dimensional transthoracic and
      transesophageal echocardiography in the localization of mitral valve prolapse.
AB  - OBJECTIVES: The aim of this study, undertaken in patients who underwent mitral
      valve (MV) repair surgery, was to evaluate the feasibility and accuracy of 3
      dimensional (3D) transthoracic (TTE) and transesophageal (TEE) echocardiography
      in the evaluation of MV pathology. BACKGROUND: A pre-operative assessment of MV
      anatomy is essential to surgical design in patients undergoing MV repair.
      Although 2-dimensional (2D) echocardiography provides precise information
      regarding MV anatomy, 3D TTE and 3D TEE could increase the understanding of MV
      apparatus and individual scallop identification. METHODS: One-hundred-twelve
      consecutive patients with severe mitral regurgitation due to MV prolapse
      underwent a complete 2D and 3D TTE the day before surgery and a complete 2D and
      3D TEE in the operating room. Echocardiographic data obtained by the different
      techniques were compared with surgical inspection. RESULTS: Three-dimensional
      techniques were feasible in a relatively short time (3D TTE: 7 +/- 4 min; 3D TEE:
      8 +/- 3 min), with good (3D TTE 55%; 3D TEE 35%) and optimal (3D TTE 21%; 3D TEE
      45%) imaging quality in the majority of cases. Three-dimensional TEE allowed more
      accurate identification (95.6% accuracy) of all MV lesions in comparison with
      other techniques. Three-dimensional TTE and 2D TEE had similar accuracies (90%
      and 87%, respectively), whereas the accuracy of 2D TTE (77%) was significantly
      lower. CONCLUSIONS: Three-dimensional TTE and TEE are feasible and useful methods
      in identifying the location of MV prolapse. They were superior in the description
      of pathology in comparison with the corresponding 2D techniques and should be
      regarded as an important adjunct to standard 2D examinations in decisions
      regarding MV repair.

PMID- 17174194
TI  - Insulin resistance as a determinant of platelet activation in obese women.
AB  - OBJECTIVES: We tested the hypothesis that insulin resistance, per se, contributes
      to increased platelet activation in obesity, independently of underlying
      inflammation. BACKGROUND: Obesity, insulin resistance, and atherosclerosis are
      closely linked phenomena associated with low-grade inflammation. Obesity is
      associated with persistent platelet activation in otherwise healthy women.
      METHODS: We performed a cross-sectional study in 40 obese and 20 non-obese
      healthy women using urinary thromboxane metabolite excretion as a non-invasive
      index of platelet activation. An index of insulin sensitivity, S(I), and plasma
      adiponectin, C-reactive protein (CRP), and CD40 ligand (CD40L) levels were
      measured. RESULTS: Obese women had significantly (p < 0.0001) higher 11-dehydro
      thromboxane B2 (11-dehydro-TXB2) excretion (median 718 vs. 211 pg/mg creatinine),
      CRP (1.13 vs. 0.48 mg/l), and CD40L levels (4.45 vs. 0.90 ng/ml) than controls.
      Obese women had lower S(I) (median 2.51 vs. 5.0 10(4) min(-1)/[microU/ml], p <
      0.002) and adiponectin (6.3 vs. 10 microg/ml, p < 0.01) than control subjects. On
      multiple regression analysis, waist-to-hip ratio (beta = 0.27, p < 0.05) and S(I)
      (beta = -0.72, p < 0.04) predicted 11-dehydro-TXB2 excretion rate, independently
      of adiponectin, CRP, CD40L, and lipid patterns. In order to investigate the cause
      effect relationship of these associations, we examined the effects of a 12-week
      weight loss program or a 3-week pioglitazone treatment on urinary 11-dehydro-TXB2
      in 10 women with impaired S(I) and visceral obesity. Successful weight loss (0.6
      kg loss/week) achieved in 5 subjects was associated with increased S(I) (+92%)
      and decreased CD40L (-27%), CRP (-37%), and 11-dehydro-TXB2 (-53%) (p < 0.05).
      Consistently, improvement of insulin sensitivity achieved with pioglitazone
      significantly decreased urinary 11-dehydro-TXB2 excretion (-43%, p < 0.05)
      without changes in body weight. CONCLUSIONS: Insulin resistance is a major
      determinant of platelet activation in female obesity.

PMID- 17174195
TI  - The novel phosphodiesterase inhibitor NM-702 improves claudication-limited
      exercise performance in patients with peripheral arterial disease.
AB  - OBJECTIVES: The current study tested the hypothesis that NM-702 improves
      treadmill exercise performance in peripheral arterial disease patients with
      claudication-limited exercise performance. BACKGROUND: Patients with claudication
      experience significant disability, owing to their exercise limitation.
      Therapeutic options to improve exercise performance in these patients are
      limited. NM-702 is a novel drug that inhibits phosphodiesterase as well as
      thromboxane A2 synthase. METHODS: This study was a randomized, multi-center,
      placebo-controlled, double-blind trial. Patients were randomized to receive 24
      weeks of twice-daily treatment with either placebo (intent to treat population, n
      = 130), 4 mg NM-702 (n = 126), or 8 mg NM-702 (n = 130). RESULTS: After 24 weeks
      of treatment, 8 mg NM-702 was associated with a statistically significant
      increased peak walking time on a graded treadmill as compared with placebo (p =
      0.004). Peak walking time after 24 weeks was increased by 17.1 +/- 49.0% in the
      placebo arm, 22.1 +/- 60.1% in the 4-mg NM-702 arm, and 28.1 +/- 50.5% in the 8
      mg NM-702 arm. NM-702 at the 8-mg dose for 24 weeks was associated with
      statistically significant improvements in the treadmill claudication onset time
      as compared with placebo. In addition, as compared with placebo, NM-702 improved
      the physical component and physical functioning scores of the Medical Outcomes
      Study 36-Item Short Form and the walking distance and stair climbing domains of
      the Walking Impairment Questionnaire. NM-702 was generally well tolerated, but
      adverse events typical of vasodilators were common. CONCLUSIONS: NM-702 used for
      24 weeks by patients with claudication was associated with improvements in
      laboratory- and ambulatory-based exercise performance.

PMID- 17174196
TI  - Complications of right heart catheterization procedures in patients with
      pulmonary hypertension in experienced centers.
AB  - OBJECTIVES: This study sought to assess the risks associated with right heart
      catheter procedures in patients with pulmonary hypertension. BACKGROUND: Right
      heart catheterization, pulmonary vasoreactivity testing, and pulmonary
      angiography are established diagnostic tools in patients with pulmonary
      hypertension, but the risks associated with these procedures have not been
      systematically evaluated in a multicenter study. METHODS: We performed a
      multicenter 5-year retrospective and 6-month prospective evaluation of serious
      adverse events related to right heart catheter procedures in patients with
      pulmonary hypertension, as defined by a mean pulmonary artery pressure >25 mm Hg
      at rest, undergoing right heart catheterization with or without pulmonary
      vasoreactivity testing or pulmonary angiography. RESULTS: During the
      retrospective period, 5,727 right heart catheter procedures were reported, and
      1,491 were reported from the prospective period, for a total of 7,218 right heart
      catheter procedures performed. The results from the retrospective and the
      prospective analyses were almost identical. The overall number of serious adverse
      events was 76 (1.1%, 95% confidence interval 0.8% to 1.3%). The most frequent
      complications were related to venous access (e.g., hematoma, pneumothorax),
      followed by arrhythmias and hypotensive episodes related to vagal reactions or
      pulmonary vasoreactivity testing. The vast majority of these complications were
      mild to moderate in intensity and resolved either spontaneously or after
      appropriate intervention. Four fatal events were recorded in association with any
      of the catheter procedures, resulting in an overall procedure-related mortality
      of 0.055% (95% confidence interval 0.01% to 0.099%). CONCLUSIONS: When performed
      in experienced centers, right heart catheter procedures in patients with
      pulmonary hypertension are associated with low morbidity and mortality rates.

PMID- 17174197
TI  - Endothelial progenitor cells participate in nicotine-mediated angiogenesis.
AB  - OBJECTIVES: We aimed to determine the role of endothelial progenitor cells (EPCs)
      in cholinergic angiogenesis. BACKGROUND: Recently, we provided evidence for a new
      angiogenic pathway mediated by endothelial nicotinic acetylcholine receptors
      (nAChR). Increasing evidence suggests that circulating EPCs also contribute to
      postnatal neovascularization by homing to sites of neovascularization, a process
      termed postnatal vasculogenesis. Therefore, we investigated whether nAChR
      activation increases mobilization and/or recruitment of EPCs to a site of
      angiogenesis. METHODS: To identify EPCs from reservoirs both inside and outside
      of the bone marrow and to avoid the adverse effects of total body irradiation, we
      employed a murine parabiosis model with tie-2-LacZ FvB/N mice connected to wild
      type FvB/N mice and induced unilateral hind limb ischemia in the wild-type
      animal. RESULTS: Administration of nicotine increased capillary density in the
      ischemic hind limb, and increased soluble Kit ligand plasma levels. The effect of
      systemic administration was greater than that of local delivery of nicotine (45%
      vs. 76% increase in capillary density by comparison to vehicle control,
      intramuscular vs. oral administration of nicotine; p < 0.05). Ischemia-induced
      incorporation of EPC in the control group was rare, but was increased 5-fold by
      systemic administration of nicotine. Exposure to nicotine in vitro increased EPC
      count and EPC transmigration. Finally, systemic administration of nicotine
      increased EPC number in the bone marrow and spleen during hind limb ischemia.
      CONCLUSIONS: Nicotine treatment increased the number of EPCs in the bone marrow
      and spleen, and increased their incorporation into the vasculature of ischemic
      tissue. Administration of nicotine increased markers of EPC mobilization. This
      study indicates that the known angiogenic effect of nicotine may be mediated in
      part by mobilization of precursor cells.

PMID- 17174198
TI  - The Janus face of nicotinic angiogenesis.

PMID- 17174199
TI  - Highlights of the 2006 scientific sessions of the European Society of Cardiology:
      Barcelona, Spain, September 2-5, 2006.

PMID- 17174200
TI  - The year in heart failure.

PMID- 17174201
TI  - Late clinical events after clopidogrel discontinuation may limit the benefit of
      drug-eluting stents: an observational study of drug-eluting versus bare-metal
      stents.
AB  - OBJECTIVES: We sought to define the incidence of late clinical events and late
      stent thrombosis in patients treated with drug-eluting (DES) versus bare-metal
      stents (BMS) after the discontinuation of clopidogrel as well as their timing and
      outcome. BACKGROUND: There is growing concern that delayed endothelialization
      after DES implantation may lead to late stent thrombosis and related myocardial
      infarction (MI) or death. However, event rates and outcomes after clopidogrel
      discontinuation versus BMS are unknown. METHODS: A consecutive series of 746
      nonselected patients with 1,133 stented lesions surviving 6 months without major
      events were followed for 1 year after the discontinuation of clopidogrel.
      Patients were assigned randomly 2:1 to DES versus BMS in BASKET (Basel Stent
      Kosten Effektivitats Trial). The primary focus of this observation was cardiac
      death/MI. RESULTS: Rates of 18-month cardiac death/MI were not different between
      DES and BMS patients. However, after the discontinuation of clopidogrel (between
      months 7 and 18), these events occurred in 4.9% after DES versus 1.3% after BMS
      implantation. Target vessel revascularization remained lower after DES, resulting
      in similar rates of all clinical events for this time period (DES 9.3%, BMS
      7.9%). Documented late stent thrombosis and related death/target vessel MI were
      twice as frequent after DES versus BMS (2.6% vs. 1.3%). Thrombosis-related events
      occurred between 15 and 362 days after the discontinuation of clopidogrel,
      presenting as MI or death in 88%. CONCLUSIONS: After the discontinuation of
      clopidogrel, the benefit of DES in reducing target vessel revascularization is
      maintained but has to be balanced against an increase in late cardiac death or
      nonfatal MI, possibly related to late stent thrombosis.

PMID- 17174202
TI  - Late ischemic events after clopidogrel cessation following drug-eluting stenting:
      should we be worried?

PMID- 17174203
TI  - Wilbur is back.

PMID- 17174204
TI  - The ACCF/AHA scientific statement on syncope needs rethinking.

PMID- 17174206
TI  - Examining the concept of preserved systolic function.

PMID- 17174209
TI  - Degenerative valve disease.

PMID- 17174207
TI  - Effect of door-to-balloon time on patient mortality.

PMID- 17174211
TI  - American College of Cardiology 2006 principles to guide physician pay-for
      performance programs: a report of the American College of Cardiology Work Group
      on Pay for Performance (A Joint Working Group of the ACC Quality Strategic
      Direction Committee and the ACC Advocacy Committee).

PMID- 17174212
TI  - [Treatment by lepirudin and acenocoumarol of heparin induced thrombocytopenia
      after valvular surgery: a word of caution].
AB  - The diagnosis and treatment of type II heparin-induced thrombocytopenia (HIT)
      after valvular surgery raise difficult issues due to the substitution of heparin
      by other anticoagulants. A 50-year-old man with hepatic cirrhosis and acute
      infective endocarditis underwent aortic valve replacement. On the 4th
      postoperative day platelet count decreased to 50 g/l. Platelet aggregation was
      demonstrated in vitro with unfractioned and low molecular weigh heparins and
      danaparoid sodium. As serum creatinine was 94 micromol/l, lepirudine (r-hirudin)
      was administered at recommended doses. However, six hours later hirudinaemia
      estimated by ecarin-clotting time was 3 mg/l and lepirudine dose had to be
      divided by 15 in order to reach therapeutic levels. Similarly, INR increased up
      to 6,7 on the 11th postoperative day after acenocoumarol 1 mg daily was
      administered. Despite the presence of oesophageal, gastric and duodenal lesions
      at risk of haemorrhage no bleeding was detected. The reasons for overdosage are
      discussed. The necessity of measurement or calculation of creatinine clearance
      before lepirudine prescription and frequent hirudinaemia during treatment is
      emphasized.

PMID- 17174213
TI  - [Thrombosis of a cardiopulmonary bypass circuit despite recommended
      hypocoagulation with danaparoid during the acute phase of type II heparin-induced
      thrombocytopenia].
AB  - A 36-year-old patient was admitted to our hospital with ischaemic stroke. The
      initial assessment allowed the diagnosis of an antiphospholipid syndrome (APS)
      and an intracardiac mass suggestive of a heart tumour. The patient was treated
      with unfractionated heparin. Type II heparin-induced thrombopenia (HIT) was
      diagnosed on the 18th day of therapy. Given the risk of stroke recurrence it was
      decided to remove the cardiac tumour surgically. Cardiopulmonary bypass (CPB) was
      performed using danaparoid in a state of deep hypothermia, in accordance with the
      well-established protocol in use in our department. As the CPB and surgical
      procedure came to an end a massive thrombus began forming in the circuit,
      requiring immediate displacement of the CPB cannulae. The anti-Xa activity level
      obtained had been considered effective at an estimated 1.20 IU/ml, although, the
      level recommended by Magnani is between 1.50 and 2.0 IU/ml. There was no clinical
      consequence and postoperative recovery was uneventful. The discrepancy between
      the satisfactory level of anti-Xa activity and the thrombus formation in the CPB
      circuit raises the issue of the diversity of published anticoagulation protocols,
      the difficulty to extrapolate within a surgical team, the need for intensive
      laboratory monitoring within a narrow therapeutic range, as well as the patient
      profiles variability with concurrent disorders complicating their clinical
      management.

PMID- 17174214
TI  - [Intra-aortic balloon pumping and heparin-induced thrombocytopenia].
AB  - Thrombocytopenia is frequently reported in the presence of intra-aortic balloon
      pumping (IABP) after cardiac surgery and in cardiology, but heparin-induced
      thrombocytopenia (HIT) is rarely responsible of it in this circumstance. A case
      report if HIT in a patient with IABP is presented. This case emphasised the
      difficulty in diagnosis of HIT in this situation. An acute decrease in platelet
      count lasting after removal of IABP could suggest the diagnosis of HIT when other
      origins for thrombocytopenia are excluded.

PMID- 17174215
TI  - [Use of heparin and platelet GPIIbIIIa inhibitor tirofiban for cardiac surgery in
      patients for suspicion of heparin-induced thrombocytopenia].
AB  - In a patient with heparin-induced thrombocytopenia few antithrombotic alternate
      treatments are proposed for cardiac surgery with or without cardiopulmonary
      bypass: danaparoid, lepirudine or powerful antiplatelet agent. Recently, the
      platelet GPIIbIIIa antagonist tirofiban (Aggrastat) was tested in humans. We
      reported two cases of patients operated upon for cardiac surgery with
      unfractionnated heparin (UFH) and tirofiban. The first patient underwent an off
      pump coronary artery bypass graft and the second one a mitral valvular
      replacement under cardiopulmonary bypass. Tirofiban was associated with UFH and
      aprotinine. Postoperative bleeding was in the normal range for the two types of
      surgeries and haemodynamic tolerance was good. These two case reports support the
      possibility of secure cardiac surgery under efficient platelet inhibition with
      tirofiban. The management of cardiac surgery with tirofiban without monitoring of
      platelet aggregation appeared to be more simple than with the other alternate
      antithrombotic agents.

PMID- 17174217
TI  - Computer-based blood donor screening: a status report.
AB  - There is a substantial literature suggesting that computer-assisted interviewing
      has advantages over face-to-face and written self-administration of interviews in
      venues eliciting sensitive information similar to that sought in blood donor
      history screening. We review some of the recent developments in blood donor
      history screening, the evidence suggesting that automated interviews should be
      useful, and the experience to date using computer interviews for blood donation.
      These data suggest that automated computer-assisted interviewing increases the
      elicitation of behaviors associated with the risk of transfusion-transmissible
      infection in donors, improves donor and staff satisfaction, and reduces errors
      and omissions that frequently accompany traditional interviewing methods. Food
      and Drug Administration-cleared systems for computer-assisted self-interview of
      blood donors are briefly described.

PMID- 17174216
TI  - Acetaminophen and diphenhydramine premedication for allergic and febrile
      nonhemolytic transfusion reactions: good prophylaxis or bad practice?
AB  - Febrile nonhemolytic and allergic reactions are the most common transfusion
      reactions, but usually do not cause significant morbidity. In an attempt to
      prevent these reactions, US physicians prescribe acetaminophen or diphenhydramine
      premedication before more than 50% of blood component transfusions. Acetaminophen
      and diphenhydramine are effective therapies for fever and allergy, respectively,
      so their use in transfusion has some biologic rationale. However, these
      medications also have potential toxicity, particularly in ill patients, and in
      the studies performed to date, they have failed to prevent transfusion reactions.
      Whether the benefits of routine prophylaxis with acetaminophen and
      diphenhydramine outweigh their risks and cost requires reexamination,
      particularly in light of the low reaction rates reported at many institutions
      even when premedication is not prescribed.

PMID- 17174218
TI  - Transfusion-transmitted cytomegalovirus: lessons from a murine model.
AB  - Transfusion-transmitted cytomegalovirus (CMV) infection (TT-CMV) continues to
      complicate blood transfusion therapy, which can lead to severe morbidity or
      mortality in immunocompromised or immuno-immature recipients. The biological
      mechanisms that underlie TT-CMV (eg, viral latency in donor monocytes or
      stimulatory signals in the transfusion recipient leading to cytomegalovirus
      reactivation) are difficult to study in humans, but can be addressed in animal
      models. In this review, we discuss a mouse blood transfusion model, which can be
      used to investigate these issues as well as to validate methods to prevent TT-CMV
      in at-risk patients.

PMID- 17174219
TI  - Anticoagulants and their reversal.
AB  - In an exciting era with many alternatives to the old anticoagulants heparin and
      warfarin emerging on the scene, awareness of the possibility to reverse their
      effect is mandatory. In this review, the traditional antidotes for warfarin
      (vitamin K, plasma, and prothrombin complex concentrate) and for heparin
      (protamine) are described together with the newer alternatives (recombinant
      activated factor VII, concatameric peptides, and recombinant platelet factor 4).
      For some of the newer anticoagulants, possible antidotes have been identified,
      whereas other alternatives have been discarded. There is a very limited
      experience of deamino-d-arginine vasopressin or a von Willebrand factor VIII
      concentrate to counteract hirudin. The small direct thrombin inhibitors may be
      reversed with activated prothrombin complex concentrate but not with recombinant
      activated factor VII, whereas the latter agent appears to be effective against
      the pentasaccharides and the recombinant nematode anticoagulant protein C2.
      Additional options that may become available in the future are also discussed
      briefly.

PMID- 17174220
TI  - Increasing patient safety and efficiency in transfusion therapy using formal
      process definitions.
AB  - The administration of blood products is a common, resource-intensive, and
      potentially problem-prone area that may place patients at elevated risk in the
      clinical setting. Much of the emphasis in transfusion safety has been targeted
      toward quality control measures in laboratory settings where blood products are
      prepared for administration as well as in automation of certain laboratory
      processes. In contrast, the process of transfusing blood in the clinical setting
      (ie, at the point of care) has essentially remained unchanged over the past
      several decades. Many of the currently available methods for improving the
      quality and safety of blood transfusions in the clinical setting rely on informal
      process descriptions, such as flow charts and medical algorithms, to describe
      medical processes. These informal descriptions, although useful in presenting an
      overview of standard processes, can be ambiguous or incomplete. For example, they
      often describe only the standard process and leave out how to handle possible
      failures or exceptions. One alternative to these informal descriptions is to use
      formal process definitions, which can serve as the basis for a variety of
      analyses because these formal definitions offer precision in the representation
      of all possible ways that a process can be carried out in both standard and
      exceptional situations. Formal process definitions have not previously been used
      to describe and improve medical processes. The use of such formal definitions to
      prospectively identify potential error and improve the transfusion process has
      not previously been reported. The purpose of this article is to introduce the
      concept of formally defining processes and to describe how formal definitions of
      blood transfusion processes can be used to detect and correct transfusion process
      errors in ways not currently possible using existing quality improvement methods.

PMID- 17174221
TI  - Blood group antibodies and their significance in transfusion medicine.
AB  - The discovery of almost universally present naturally occurring antibodies in
      blood plasma led to the discovery of the ABO blood group system which remains,
      more than 100 years later, the most important and clinically significant of all
      blood groups. Blood group antibodies play an important role in transfusion
      medicine, both in relation to the practice of blood transfusion and in pregnancy,
      but not all are clinically significant. Clinically significant antibodies are
      capable of causing adverse events following transfusion, ranging from mild to
      severe, and of causing hemolytic disease of the fetus and newborn following
      placental transfer from mother to fetus. Assessing the clinical significance of
      antibodies relies heavily on mode of reactivity and historical data relating to
      specificity; functional assays are sometimes employed. The principals of
      methodology for blood typing and antibody identification have changed little over
      the years, relying mainly on serological methods involving red cell
      agglutination. The recent advent of blood typing using DNA technology, although
      still in relative infancy, will surely eventually supersede serology. However,
      deciding on the clinical significance of an antibody when compatible blood is not
      immediately available is likely to remain as one of the most common dilemmas
      facing transfusion practitioners.

PMID- 17174223
TI  - Lipoprotein-associated phospholipase A2 A379V variant is associated with body
      composition changes in response to exercise training.
AB  - Lipoprotein-associated PLA2 (Lp-PLA2) hydrolyses the sn-2 position of
      glycerophospholipids, in particular platelet activating factor (PAF), generating
      significant amounts of Lyso-PAF which in turn, via a remodelling pathway, can
      generate arachidonic acid (AA) from alkyl-acyl-glycerophosphorylcholine. AA is a
      precursor for prostaglandin synthesis, which regulates adipogenesis through the
      peroxisome proliferator-activated receptor subfamily. AA may also modulate
      skeletal muscle growth. We investigated the association of the PLA2G7 A379V
      variant with changes in body composition in a longitudinal study of 123 male
      Caucasian army recruits over 10 weeks of intensive physical training. There was
      no effect of genotype on baseline measures. However, after exercise training,
      homozygosity for the 379V allele was associated with a decrease in percentage
      adipose tissue mass (-3.61+/-1.14%), compared to AV (-1.67+/-0.38%) and AA (
      1.09+/-0.24%) genotypes (p=0.01), and a significant mean increase (3.51+/-1.17%)
      in percentage lean mass, compared to AV (1.64+/-0.38%) and AA (1.10+/-0.24%)
      recruits (p=0.02). The association of this genotype with changes in body
      composition after training suggests a novel role for Lp-PLA2.

PMID- 17174222
TI  - A one-year study comparing the efficacy and safety of rosiglitazone and
      glibenclamide in the treatment of type 2 diabetes.
AB  - BACKGROUND AND AIM: This study was designed to compare the efficacy of
      rosiglitazone and glibenclamide in individuals with type 2 diabetes over a 12
      month period. METHODS AND RESULTS: A total of 598 patients were randomized to
      double-blind treatment for 52 weeks with rosiglitazone 4 mg/d (n=200),
      rosiglitazone 8 mg/d (n=191) or glibenclamide (n=207; dose adjusted up to 15 mg/d
      over the first 12 weeks according to clinical response). Changes in fasting
      plasma glucose (FPG), haemoglobin A1c (HbA1c), fasting insulin and its precursor
      peptides, and lipids were measured and safety was evaluated. Significant
      reductions in HbA1c levels at 52 weeks compared with baseline were seen in all
      treatment groups (rosiglitazone 4 mg/d=-0.3%, P=0.0003; rosiglitazone 8 mg/d=
      0.5%, P<0.0001; glibenclamide=-0.7%, P<0.0001). Mean FPG levels were also
      significantly reduced in all treatment groups (rosiglitazone 4 mg/d=-1.4 mmol/l;
      rosiglitazone 8 mg/d=-2.3 mmol/l; glibenclamide=-1.7 mmol/l; P<0.0001 vs.
      baseline for all treatments). Rosiglitazone therapy reduced plasma insulin,
      proinsulin, split proinsulin and free fatty acid levels compared with
      glibenclamide. Rosiglitazone improved insulin resistance while a worsening was
      seen with glibenclamide. Total:high-density lipoprotein cholesterol ratios were
      reduced with glibenclamide and unchanged with rosiglitazone. All treatments were
      generally well tolerated. CONCLUSIONS: The efficacy of rosiglitazone 8 mg/d in
      improving glycaemic control in patients with type 2 diabetes is comparable to
      that of glibenclamide. However, rosiglitazone reduced insulin resistance and
      proinsulin levels whereas glibenclamide use was associated with an increase in
      fasting insulin and proinsulin. This suggests that in the long term,
      rosiglitazone may protect the beta-cell whereas glibenclamide is likely to
      increase the burden.

PMID- 17174224
TI  - The under-use of statin in type 2 diabetic patients attending diabetic clinics in
      Italy.
AB  - BACKGROUND AND AIMS: The greatest decrease in mortality from cardiovascular
      disease (CAD) that can be achieved with 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitors (statins) is seen in patients with the highest risk for CAD,
      such as diabetics. Yet, there is evidence for inadequate use of drug therapies to
      achieve lipid goals. Our aims were to: (1) assess the prevalence of statin use in
      patients attending diabetic clinics and (2) correlate the use of statins with
      their risk and clinical status. METHODS AND RESULTS: Of 9921 patients included,
      only 20.4% of them were receiving statin therapy. Statins were more progressively
      prescribed in those with risk factors additional to that of diabetes. Patients
      under statin treatment were older, mostly type 2 diabetics, more hypertensive and
      hyperlipidemic, had a higher prevalence of both macro- and microvascular disease.
      Among those with a total cholesterol concentration above 252 mg/dl, statin
      treatment was given only to 60% of diabetic patients with prior myocardial
      infarction, 56% of those with angina, 66% of those having had prior
      revascularization procedure, 54% of those with cerebrovascular disease and 51% of
      those with peripheral artery disease. CONCLUSIONS: At least in Italy, statins are
      not prescribed to the majority of diabetic patients, and a substantial proportion
      of patients not treated with statins present significant macro- and microvascular
      complications.

PMID- 17174225
TI  - Using ankle-brachial index to detect peripheral arterial disease: prevalence and
      associated risk factors in a random population sample.
AB  - BACKGROUND AND AIM: The ankle-brachial index (ABI) is being used increasingly to
      diagnose peripheral arterial disease (PAD) that predicts cardiovascular morbidity
      and mortality. The aim of this study is to determine the prevalence of PAD and
      associated risk factors in a Spanish random population sample of age > or =40.
      METHODS AND RESULTS: PAD is defined as an ABI<0.9 in either leg. 784 participants
      of age > or =40 were randomly selected in a Spanish province. 55.4% of them were
      female. The prevalence of PAD in this sample was 10.5% (95% confidence interval
      (CI) 8.4-12.8); 9.7% in females and 11.4% in males. In logistic regression
      analyses, adjusted for age and gender, smoking per 10 pack-years (odds ratio (OR)
      1.40, 95% CI 1.23-1.58), hypertension (OR 1.85, 95% CI 1.05-3.28),
      hypercholesterolemia (OR 1.76, 95% CI 1.04-2.98), and diabetes (OR 1.80, 95% CI
      1.04-3.11) were positively associated with prevalent PAD. More than 91% of
      persons with PAD had one or more cardiovascular disease risk factors.
      CONCLUSIONS: We conclude that in our study hypertension, hypercholesterolemia,
      diabetes mellitus and smoking are associated with PAD. The majority of
      individuals with PAD had at least one important cardiovascular risk factor
      advanced enough to be considered eligible for an aggressive treatment.

PMID- 17174227
TI  - Quality of life in patients with signs and symptoms of heart failure--does
      systolic function matter?
AB  - BACKGROUND: The impaired quality of life in patients with systolic heart failure
      is well described. Less is known about patients with preserved systolic function
      (PSF) heart failure. METHODS AND RESULTS: We aimed to compare the quality of life
      in patients with PSF heart failure with that of those with left ventricular
      systolic dysfunction (LVSD) using generic and disease-specific quality-of-life
      questionnaires. Four hundred patients with signs and symptoms of heart failure
      referred for an echocardiogram to assess left ventricular function were invited
      to complete quality-of-life questionnaires. A total of 278 of 400 (69.5%)
      responses were adequate for analysis. The mean age of respondents was 72.5 (10)
      years; 132 (47%) were male. A total of 189 of 278 (68%) had PSF, and 89 of 278
      (32%) had left ventricular systolic dysfunction (LVSD). Both groups were well
      matched for age, but there were more women in the PSF group (58% vs. 40%). No
      significant differences were found in the quality of life between PSF and LVSD
      patients. Women had significantly worse quality of life compared with men in both
      groups. CONCLUSION: Patients with PSF are an important subgroup of heart failure
      patients whose quality of life is as impaired as those with systolic dysfunction.
      These data suggest these patients warrant more care, perhaps in specialist
      clinics.

PMID- 17174226
TI  - Olive, soybean and palm oils intake have a similar acute detrimental effect over
      the endothelial function in healthy young subjects.
AB  - BACKGROUND AND AIM: Currently, more than 30% of the caloric intake in the
      Colombian population comes from vegetable oil consumption mainly by the ingestion
      of deep-fried foods. Recently, it has been reported that unsaturated fatty acid
      rich oils have a beneficial effect on the endothelial function. Nevertheless, it
      is well know that the deep-frying process alters the chemical composition of
      vegetable oils and can produce adverse effects in the endothelial function.
      OBJECTIVE: To evaluate the acute effect of the ingestion of large amounts of
      olive, soybean and palm oils, fresh and at two different deep-fry levels, on the
      glucose and lipid profiles and the endothelial function. METHODS AND RESULTS: Ten
      healthy young volunteers were included in the study. After performing a baseline
      evaluation of cardiovascular risk factors and drawing a fasting blood sample,
      subjects were exposed to a randomly assigned potato soup meal containing 60 mL of
      one of three different vegetable oils (olive, soybean and palm), either fresh or
      at one of two different deep-fry levels (10 and 20 fries, respectively). Flow
      mediated vasodilation (FMD) was performed in fasting conditions and 3h after the
      intake of the oil rich meal. Furthermore, blood samples were taken at these
      stages for the lipid profiles and plasma glucose determinations. All the meals
      resulted in a similar acute endothelial impairment (FMD decrease of 32.1%,
      confidence interval [CI] 95%, 28.0-36.2) and postprandial increase in
      triglycerides (27.03%, CI 95%, 20.5-33.3), independently of the type of oil
      ingested (p=0.44) and regardless of its deep-fry level (p=0.62). No correlation
      was found between endothelial impairment and postprandial triglyceride increment
      (r=-0.22, p=0.09). CONCLUSIONS: No difference was found in the acute adverse
      effect of the ingestion of different vegetable oils on the endothelial function.
      All the vegetable oils, fresh and deep-fried, produced an increase in the
      triglyceride plasma levels in healthy subjects.

PMID- 17174228
TI  - Racial differences in the characteristics of patients admitted for acute
      decompensated heart failure and their relation to outcomes: results from the
      OPTIME-CHF trial.
AB  - BACKGROUND: Recent data suggest that differences in response to therapy and
      survival exist between African Americans and Caucasians with heart failure.
      Whether these differences exist in acute decompensated heart failure (ADHF) is
      uncertain. METHODS AND RESULTS: We analyzed data from the OPTIME-CHF (Outcomes of
      a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart
      Failure) study, a randomized trial of intravenous milrinone versus placebo in 949
      patients hospitalized with ADHF. We evaluated differences in clinical
      characteristics, outcomes, and response to milrinone therapy in African American
      patients compared with Caucasians. The primary end point of OPTIME-CHF was days
      hospitalized for cardiovascular causes or death within 60 days of randomization.
      Thirty-three percent (n = 310) of patients were African American. African
      American patients were younger (57 vs. 70 years, P < .0001) and more likely to
      have non-ischemic cardiomyopathy (74% vs. 36%, P < .0001). In unadjusted
      analysis, African American patients had a lower 60-day mortality (5% vs. 12%, P =
      .0004) and tended to have better overall clinical outcomes. After adjustment for
      baseline differences, however, these differences were no longer significant. We
      found no differential effect of milrinone therapy by race. CONCLUSION: African
      American patients with acute decompensated heart failure present with a different
      clinical profile than Caucasian patients. Although unadjusted clinical outcomes
      are better for African Americans presenting with ADHF, these differences
      diminished after adjustment for baseline characteristics.

PMID- 17174229
TI  - Expansion of heart failure device therapy into a rural indigent population in
      Louisiana: potential economic and health policy implications.
AB  - BACKGROUND: Research regarding the use of implantable devices in patients with
      congestive heart failure (CHF) has shown mortality benefits. The Center for
      Medicare and Medicaid Services (CMS) approved new criteria for expanding coverage
      for such therapies. The purpose of this study was to determine the percentages of
      CHF patients in a rural, indigent heart failure population that would be eligible
      for implantable defibrillators (ICD) and cardiac resynchronization therapy (CRT)
      based on the new CMS criteria. METHODS AND RESULTS: The new CMS guidelines were
      applied to information compiled in a database for 451 CHF disease management
      patients, at Leonard J. Chabert Medical Center. Results show that, annually, 32%
      of the newly identified CHF patient population would be eligible for ICD therapy
      and 7.3% would be eligible for CRT therapy. CONCLUSIONS: Providers of health care
      to the indigent may lack sufficient resources for the devices and the
      infrastructure for device implantation and follow-up.

PMID- 17174230
TI  - Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and
      functional status in patients with chronic heart failure.
AB  - BACKGROUND: Insulin resistance is present in the setting of congestive heart
      failure. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with
      both insulinotropic and insulinomimetic properties. METHODS AND RESULTS: We
      investigated the safety and efficacy of a 5-week infusion of GLP-1 (2.5
      pmol/kg/min) added to standard therapy in 12 patients with New York Heart
      Association class III/IV heart failure and compared the results with those of 9
      patients with heart failure on standard therapy alone. Echocardiograms, maximum
      myocardial ventilation oxygen consumption (VO2 max), 6-minute walk test, and
      Minnesota Living with Heart Failure quality of life score (MNQOL) were assessed.
      Baseline demographics, background therapy, and the degree of left ventricular
      dysfunction were similar between groups. GLP-1 significantly improved left
      ventricular ejection fraction (21 +/- 3% to 27 +/- 3% P < .01), VO2 max (10.8 +/-
      .9 ml/O2/min/kg to 13.9 +/- .6 ml/O2/min/kg; P < .001), 6-minute walk distance
      (232 +/- 15 m to 286 +/- 12 m; P < .001) and MNQOL score (64 +/- 4 to 44 +/- 5; P
      < .01). Benefits were seen in both diabetic and non-diabetic patients. There were
      no significant changes in any of the parameters in the control patients on
      standard therapy. GLP-1 was well tolerated with minimal episodes of hypoglycemia
      and gastrointestinal side effects. CONCLUSION: Chronic infusion of GLP-1
      significantly improves left ventricular function, functional status, and quality
      of life in patients with severe heart failure.

PMID- 17174231
TI  - Impact of obesity on the health status of heart failure patients.
AB  - BACKGROUND: Obesity is a recognized, preventable risk factor for the development
      of heart failure (HF); however, little is understood about its effects on
      patients with established HF. Furthermore, few researchers have assessed
      obesity's effect on the health status of established HF patients. This study
      evaluated the influence of obesity on the health status, at baseline and 1 year
      later, on patients with established HF. METHODS AND RESULTS: Comprehensive
      clinical data, health status, and obesity classification of 543 HF outpatients
      from 13 centers was assessed at baseline and 1 year later. Health status was
      quantified with the generic Short Form-12 and disease-specific Kansas City
      Cardiomyopathy Questionnaire Overall Summary score. Cross-sectional and
      longitudinal risk-adjusted general linear models were computed comparing the
      health status of patients who were classified as either underweight, normal
      weight, overweight, or obese. Obesity classification was not significantly
      associated with patients' baseline health status and did not predict 1-year
      health status. CONCLUSIONS: Although obesity has been reported to confer a
      survival advantage to patients with HF, it was not associated with better health
      status at baseline, or after 1 year, in our cohort. Better understanding of the
      relationship among HF, body weight, and health status is needed before evidence
      based recommendations can be made regarding weight management for HF patients.

PMID- 17174233
TI  - Temporal variation in optimal atrioventricular and interventricular delay during
      cardiac resynchronization therapy.
AB  - BACKGROUND: Tailored atrioventricular delay (AVd) and interventricular delay
      (VVd) combination improves hemodynamics in patients treated with cardiac
      resynchronization therapy (CRT). Whether tailored AVd-VVd combination changes
      over time is not known. METHODS AND RESULTS: Twenty-two patients (18 M, aged 69.9
      +/- 12.5 years, New York Heart Association class III, QRS > or = 130 ms, ejection
      fraction 29.6 +/- 8.8%) were implanted with a biventricular device with
      programmable VVd. Myocardial performance index (MPI) was evaluated during pacing
      at different VVds and AVds at baseline and after 6 and 12 months. The optimal AVd
      VVd combination was identified by the minimum MPI. After optimization, the
      appropriate AVd-VVd combination was programmed in each patient. MPI at 6-month
      follow-up after optimization was significantly higher compared with baseline (.79
      +/- .21 vs. .59 +/- .15, P < .05). Re-optimization of AVd-VVd combination was
      required after 6 months in 21 of 22 (95%) patients. Re-optimization significantly
      reduced MPI compared with the value prior to re-optimization (.56 +/- .15 vs. .79
      +/- .21, P < .05). The MPI remained unchanged at 12-month compared with 6-month
      follow-up (.59 +/- .19 vs. .56 +/-.15, P = NS). Clinical symptoms and reverse
      left ventricular remodeling were sustained at 6-month and 12-month follow-up.
      CONCLUSION: Optimal AVd and VVd combination changes over time in patients with
      heart failure. Sustained improvement in clinical symptoms and reverse left
      ventricular remodeling after CRT are not temporally associated with improvement
      in MPI.

PMID- 17174232
TI  - Use of a novel ultrafiltration device as a treatment strategy for diuretic
      resistant, refractory heart failure: initial clinical experience in a single
      center.
AB  - BACKGROUND: The System 100 UF device allows ultrafiltration (UF) via peripheral
      access and is approved for use in heart failure (HF), although clinical trials
      defining optimal target population and clinical utility are lacking. We report
      our initial experience with clinical use of this system in very advanced,
      diuretic resistant HF patients. METHODS AND RESULTS: Eleven HF patients (mean age
      70 years) underwent 1 to 5 UF treatments each (total 32 UF). The goal was to
      remove 4 liters of fluid per 8-hour UF. Baseline creatinine averaged 2.2 mg/dL
      (range .9-3.2) while estimated glomerular filtration rates (GFRs) averaged 38
      mL/min (range 20-87). Nine patients (82%) had moderate (GFR 30-59; n = 3) or
      severe (GFR <30; n = 6) renal dysfunction. Nine patients (82%) had documented
      right ventricular dysfunction, 6 with severe tricuspid regurgitation. Average
      daily intravenous furosemide dose prior to UF was 258 mg (range 80-480). Patients
      had received nesiritide (n = 4), dopamine (n = 4), and zaroxylyn (n = 7) prior to
      UF. Of the 32 UF treatments, 13 (41%) removed >3500 mL, 11 (34%) removed 2500
      3500 mL, and 8 (25%) removed <2500 mL. Only one UF treatment (3%) was aborted due
      to hypotension. There were no significant complications related to UF. Five
      patients (45%) experienced an increase in creatinine of >.3 mg/dl. Five patients
      required dialysis for persistent diuretic resistant volume overload or uremic
      symptoms. Six-month mortality was 55%. CONCLUSIONS: Peripheral UF safely but
      variably removed fluid. In this very high-risk, advanced HF population, 45% of
      patients developed worsening renal function during UF therapy. Controlled studies
      are needed to determine the impact of UF on renal function and outcomes in high
      risk populations such as this.

PMID- 17174234
TI  - Catabolism of adenine nucleotides favors adenosine production following exercise
      in patients with chronic heart failure.
AB  - BACKGROUND: Adenosine 5'-triphosphate is catabolized to adenosine 5'
      monophosphate (AMP), which is further degraded by 2 pathways: deamination to
      inosine 5'-monophosphate and ammonia by AMP deaminase, or dephosphorylation to
      adenosine and inorganic phosphate by 5'-nucleotidase. Because adenosine is
      believed to be cardioprotective and we have reported that ammonia production
      decreased after exercise in patients with chronic heart failure (CHF), we
      determined if plasma adenosine levels after exercise increases in patients with
      CHF. METHODS AND RESULTS: Maximal ergometer exercise tests with expired gas
      analysis were performed in 51 patients with CHF (age = 61 +/- 2 years, New York
      Heart Association [NYHA] class I/II/III = 19/18/14) and 20 age-matched normal
      controls. Serial changes in both plasma ammonia and adenosine levels were
      determined. The ratio for delta ammonia to peak work rate became smaller
      (control, NYHA I/II/III: 0.59 +/- 0.13/0.41 +/- 0.06/0.37 +/- 0.10/0.22 +/- 0.11
      microg/dL x watts, respectively) and the ratio for delta adenosine to peak work
      rate was significantly higher in class III CHF (control, NYHA I/II/III: 0.93 +/-
      0.21/0.86 +/- 0.14/1.11 +/- 0.27/2.92 +/- 0.67 nmol/L x watts, respectively).
      CONCLUSION: In patients with CHF after exercise, the plasma levels of adenosine
      increased along with the decrease in the plasma levels of ammonia. Considering
      the physiologic cardioprotective actions of adenosine, the enhanced adenosine
      production after exercise may be an important adaptive response in patients with
      CHF.

PMID- 17174235
TI  - Clinical features of isolated ventricular noncompaction in adults long-term
      clinical course, echocardiographic properties, and predictors of left ventricular
      failure.
AB  - BACKGROUND: Isolated ventricular non-compaction (IVNC) is a rare disorder
      characterized by prominent trabecular meshwork and deep recesses. We
      retrospectively assessed the clinical characteristics and natural course of IVNC
      in adults diagnosed at our hospital. METHODS AND RESULTS: Sixty-seven adult
      patients (44 male, mean age 41 +/- 18 years) with the diagnosis of IVNC were
      evaluated in this retrospective cohort. Its prevalence was found to be .14%.
      Forty-seven patients (70%) had class I/II functional capacity. Fifty-seven
      patients (85%) had electrocardiographic abnormalities, and the most common one
      was left ventricular (LV) hypertrophy (25%). LV systolic function was depressed
      in 44 patients (66%), with a median ejection fraction (EF) of 35% (range: 20%
      48%) at diagnosis. Multiple regression analysis revealed that age at initial
      presentation, the total number of affected segments, and the ratio of non
      compaction/compaction (NC/C) were the independent predictors of LV systolic
      dysfunction. Familial occurrence of IVNC was 33%. During a mean follow-up of 30
      months (range: 9-50 months), major complications including ventricular
      tachycardia, heart failure requiring hospitalization, and cerebrovascular events
      were observed in 36%, 34%, and 9% of the patients, respectively. Ten patients
      (15%) with IVNC died in this study. LVEF at initial presentation and functional
      capacity at last visit were found to be independent predictors of mortality.
      CONCLUSION: This study suggests that IVNC is a form of cardiomyopathy with higher
      prevalence and relatively better prognosis than previously reported. Age at
      initial presentation, ratio of NC/C, and number of affected segments seem to be
      major determinants of LV systolic dysfunction, while initial LVEF and last
      functional capacity predict mortality in this cohort.

PMID- 17174236
TI  - Reducing the risk of sudden death in heart failure with beta-blockers.
AB  - BACKGROUND: Heart failure (HF) is a serious cardiovascular syndrome that affects
      nearly 5 million people in the United States. A review of clinical data
      demonstrates that sudden cardiac death (SCD) accounts for approximately one-third
      of all HF deaths. This fatal outcome typically involves an unexpected electrical
      event leading to sustained cardiac arrhythmias resulting in cardiovascular
      collapse. METHODS AND RESULTS: A systematic review of the literature was
      performed to serve as the basis for this review. Factors contributing directly to
      incidence of SCD in the HF population may include significant remodeling of the
      left ventricle (hypertrophy, dilation, and fibrosis) in addition to increased
      sympathetic activation. Using specific therapies to limit these mechanisms are
      beneficial in the HF patient by preventing SCD. Beta-blockers play a key role in
      the prevention of SCD for patients with HF by limiting the effects of circulating
      norepinephrine and by reducing left ventricular remodeling. CONCLUSIONS: This
      review outlines the potential mechanisms and contributing factors of SCD in
      patients with HF and the impact of beta-blocker usage in the prevention of this
      fatal outcome for this growing patient population.

PMID- 17174237
TI  - Hemodynamic and neurohormonal predictors and consequences of the development of
      atrial fibrillation in dogs with chronic heart failure.
AB  - BACKGROUND: Heart failure increases the risk of atrial fibrillation (AF), which
      frequently results in heart failure progression. This prospective study examined
      the contribution of hemodynamic and neurohormonal activation to the spontaneous
      occurrence of AF in heart failure, and assessed the effects of AF on left
      ventricular (LV) function and neurohormonal activation. METHODS AND RESULTS:
      Heart failure (LV ejection fraction [LVEF] 25%-30%) was induced in 27 dogs via
      sequential coronary microembolizations. Hemodynamic and neurohormonal
      measurements were performed at 1 month (prior to development of AF) and 4 months
      post-embolization. During the time between measurements, 10 dogs developed
      spontaneous AF. Plasma norepinephrine concentration (PNE) at 1 month was higher
      in animals that subsequently developed AF (576 + 101 vs. 425 + 197 pg/mL, P =
      .03). There were no significant differences between the groups in 1-month LV end
      diastolic pressure (LVEDP), pulmonary artery wedge pressure (PAWP), cardiac
      output, end-diastolic volume (EDV), LVEF, or plasma renin activity (PRA). At 4
      months, cardiac output was lower (2.1 + .4 vs. 2.6 + .6 L/h, P = .02) and PNE was
      higher (1036 + 857 vs. 508 + 288 pg/mL, P = .03) in dogs with AF versus those in
      sinus rhythm. There were no significant differences between groups in 4-month
      LVEDP, PAWP, EDV, LVEF, or PRA. CONCLUSION: Spontaneous AF in heart failure was
      preceded by a significant increase in PNE. In animals that developed AF, there
      was a further decline in cardiac output and increase in PNE.

PMID- 17174239
TI  - Some methodologic issues in validation of prognostic models.

PMID- 17174238
TI  - Direct effects of 3 combinations of enalapril, metoprolol, and spironolactone on
      cardiac remodeling in dilated cardiomyopathic hamsters.
AB  - BACKGROUND: In congestive heart failure, enalapril (E), metoprolol (M), and
      spironolactone (S) improve survival. Their direct effects on cardiac remodeling,
      when administered in combination, remain to be assessed. METHODS AND RESULTS: One
      hundred and five cardiomyopathic hamsters were divided into 5 groups (control, E,
      E-M, E-S, E-M-S) and treated from 150 to 240 days of age (E: 3 mg/kg, M: 1 mg/kg,
      S: 20 mg/kg). Cardiac and systemic hemodynamics, and cardiac remodeling were
      investigated. There was no difference between groups on blood pressure. Compared
      with C, both S-treated groups significantly increased cardiac index (E-S: +49%; E
      M-S: +46%). Compared with C, E significantly decreased left ventricular (LV)
      cavity area (-10%). Compared with E, all combinations significantly decreased LV
      cavity area (E-M: -13%, E-S: -22%, E-M-S: -19%) and right ventricular (RV)
      collagen density (E-M: -18%, E-S: -30%, E-M-S: -34%), and the tri-therapy
      significantly decreased LV collagen density (-18%). Compared with bi-therapies,
      the tri-therapy significantly decreased LV (-19% vs. E-M, -16% vs. E-S) and RV (
      20% vs. E-M) collagen densities. CONCLUSION: At subdepressor doses, both bi
      therapies induced similar effects on myocardial remodeling, enhancing the effects
      of E on LV cavity area and reducing RV collagen density. Compared with bi
      therapies, the tri-therapy induced additional effects on LV and RV collagen
      densities.

PMID- 17174240
TI  - Statins and sympathetic nerve activity in heart failure.

PMID- 17174242
TI  - Implementing evidence-based decision making in the private practice setting: the
      4-step process.
AB  - An important goal of EBDM is to improve outcomes where it matters the most: at
      the point of care. All dental clinicians need practical tools that facilitate
      access to the clinical information needed to enable our patients to make better
      informed choices. This article provides a 4-step guide for practical
      implementation of EBDM in the private practice setting. Step 1 is defining your
      practice purpose. Step 2 describes the use of Ethical Practice Parameters to
      guide clinical decision-making. Step 3 illustrates how to implement Ethical
      Practice Parameters. Step 4 describes a simple process for searching for
      scientific evidence. Online resources are provided and the benefits of the 4-step
      process are elucidated.

PMID- 17174243
TI  - Complete caries removal may not be indicated in symptomless deep lesions.

PMID- 17174245
TI  - Compliance with periodontal maintenance may be associated with increased tooth
      loss.

PMID- 17174246
TI  - Success of Osseotite dental implants loaded at 2 months compares favorably with
      conventional protocols.

PMID- 17174247
TI  - Computerized anesthesia delivery provides some benefit to less anxious children.

PMID- 17174248
TI  - Rofecoxib provides relief of pain following third molar extractions.

PMID- 17174249
TI  - Unclear prognosis for the autogenous tooth transplant.

PMID- 17174250
TI  - Measurement of oral health-related quality of life in children--a step forward.

PMID- 17174251
TI  - CT scans may not be indicated to analyze the distribution of the arteries in the
      lateral wall of the maxillary sinus.

PMID- 17174252
TI  - Three-dimensional ultrasonography is superior to 2-dimensional ultrasonography in
      the detection of orofacial clefts during the second trimester of pregnancy.

PMID- 17174253
TI  - The safety of amalgam compared with resin composite restorations in children
      older than 8 years showed no significant differences on neurobehavioral or nerve
      conduction studies during a 7-year follow-up.

PMID- 17174254
TI  - Bisphosphonates are associated with the development of exposed bone
      (osteonecrosis/osteopetrosis) in the oral cavity.

PMID- 17174255
TI  - Higher serum magnesium:calcium ratio may lower periodontitis risk.

PMID- 17174256
TI  - Harmful social and biological risk factors accumulated early in life influences
      the oral health of 6-year-old children.

PMID- 17174257
TI  - Female osteoporosis may be associated with composite endpoint of periodontal
      disease.

PMID- 17174259
TI  - An examination of the environmental attributes associated with pedestrian
      vehicular crashes near public schools.
AB  - This paper examines pedestrian-vehicular crashes in the vicinity of public
      schools, the severity of injuries sustained, and their relationship to the
      physical and social attributes near the schools. Multivariate models of crash
      severity and crash risk exposure were estimated as a function of social and
      physical characteristics of the area immediately surrounding schools in Baltimore
      City, Maryland. Results show that the presence of a driveway or turning bay on
      the school entrance decreases both crash occurrence and injury severity.
      Conversely, the presence of recreational facilities on the school site is
      positively associated with crash occurrence and injury severity of crashes.
      Findings related to neighborhood characteristics were mixed but the significant
      variables - transit access, commercial access, and population density - are
      generally associated with increased pedestrian demand and should be interpreted
      with care. The results of this study are relevant for Safe Routes to School
      projects and point to areas meriting further study.

PMID- 17174260
TI  - The use of hazard road signs to improve the perception of severe bends.
AB  - Collision analysis indicates that many car accidents occur when negotiating a
      bend. Excessive speed and steering wheel errors are often given by way of
      explanation. Nevertheless, the underlying origin of these dramatic errors could
      be, at least in part, a poor estimation of bend curvature. The aim of this study
      was to investigate both the assessment of bend curvature by drivers and the
      impact of symbolic road signs that indicate a hazardous bend on this assessment.
      Thus, participants first viewed a video recording showing approaching bends of
      different curvature before being asked to assess the curvature of these bends.
      This assessment could either be a verbal (symbolic control) estimation of the
      bend's curvature and risk, or a sensorimotor (subsymbolic control) estimation of
      the bend's curvature (participants were asked to turn a steering wheel to mimic
      the position that would be necessary to accurately negotiate the bend). Results
      show that very severe bends (with a radius of less than 80 m) were actually
      underestimated. This was associated with an underestimation of risk corresponding
      to these bends and a poor sensorimotor anticipation of bend curvature. Road
      signs, which indicate risk significantly improve bend assessment, but this was of
      no use for sensorimotor anticipation. Thus, other indicators need to be envisaged
      in order to also improve this level of control.

PMID- 17174261
TI  - Determination of the genetic, molecular, and biochemical basis of the Arabidopsis
      thaliana thiamin auxotroph th1.
AB  - 2-methyl-4-amino-5-hydroxymethylpyrimidine phosphate kinase/thiamin monophosphate
      pyrophosphorylase (HMPPK/TMPPase) is a key enzyme involved in thiamin
      biosynthesis. A candidate HMPPK/TMPPase gene identified in the Arabidopsis genome
      complemented the thiamin auxotrophy of the th1 mutant, thus proving that the th1
      locus corresponds to the structural gene for the HMPPK/TMPPase. Sequence
      comparisons between the wild-type HMPPK/TMPPase gene and the th1-201 mutant
      allele identified a single point mutation that caused the substitution of a
      phenylalanine for a conserved serine residue in the HMPPK domain. Functional
      analyses of the mutant HMPPK/TMPPase in Escherichia coli revealed that the amino
      acid substitution in the HMPPK domain of mutant enzyme resulted in a
      conformational change that severely compromised both activities of the
      bifunctional enzyme. Studies were also performed to identify the chloroplast as
      the specific subcellular locale of the Arabidopsis HMPPK/TMPPase.

PMID- 17174262
TI  - HD-PTP and Alix share some membrane-traffic related proteins that interact with
      their Bro1 domains or proline-rich regions.
AB  - Mammalian Alix is a multifunctional adaptor protein involved in cell death,
      receptor endocytosis, endosomal protein sorting and cell adhesion by associating
      with various proteins such as ALG-2, CIN85/Rukl/SETA, endophilins, CHMP4s and
      TSG101. HD-PTP is a paralog of Alix and a putative protein tyrosine phosphatase
      (PTP) that contains a Bro1 domain, coiled-coils, a proline-rich region (PRR) in
      addition to a PTP domain. We investigated interactions between HD-PTP and Alix
      binding proteins. In the yeast two-hybrid assay, HD-PTP showed positive
      interactions with CHMP4b/Shax1, TSG101, endophilin A1 and ALG-2 but not with
      either RabGAPLP or CIN85. We confirmed the interactions in a mammalian system by
      Strep-pulldown assays in which pulldown products from the lysates of HEK293T
      cells expressing either Strep-tagged HD-PTP alone or co-expressing with epitope
      tagged proteins were analyzed by Western blotting using specific antibodies.
      While Alix associated with both ALG-2 and TSG101 in a Ca2+-dependent manner, HD
      PTP interacted with ALG-2 Ca2+-dependently but with TSG101 Ca2+-independently.

PMID- 17174263
TI  - Effect of fibroblast activation protein and alpha2-antiplasmin cleaving enzyme on
      collagen types I, III, and IV.
AB  - The circulating enzyme, alpha2-antiplasmin cleaving enzyme (APCE), has very
      similar sequence homology and proteolytic specificity as fibroblast activation
      protein (FAP), a membrane-bound proteinase. FAP is expressed on activated
      fibroblasts associated with rapid tissue growth as in embryogenesis, wound
      healing, and epithelial-derived malignancies, but not in normal tissues. Its
      presence on stroma suggests that FAP functions to remodel extracellular matrix
      (ECM) during neoplastic growth. Precise biologic substrates have not been defined
      for FAP, although like APCE, it cleaves alpha2-antiplasmin to a derivative more
      easily cross-linked to fibrin. While FAP has been shown to cleave gelatin,
      evidence for cleavage of native collagen, the major ECM component, remains
      indistinct. We examined the potential proteolytic effects of FAP or APCE alone
      and in concert with selected matrix metalloproteinases (MMPs) on collagens I,
      III, and IV. SDS-PAGE analyses demonstrated that neither FAP nor APCE cleaves
      collagen I. Following collagen I cleavage by MMP-1, however, FAP or APCE digested
      collagen I into smaller peptides. These peptides were analogous to, yet different
      from, those produced by MMP-9 following MMP-1 cleavage. Amino-terminal sequencing
      and mass spectrometry analyses of digestion mixtures identified several peptide
      fragments within the sequences of the two collagen chains. The proteolytic
      synergy of APCE in the cleavage of collagen I and III was not observed with
      collagen IV. We conclude that FAP works in synchrony with other proteinases to
      cleave partially degraded or denatured collagen I and III as ECM is excavated,
      and that derivative peptides might function to regulate malignant cell growth and
      motility.

PMID- 17174264
TI  - Spatial distribution patterns of excitatory and inhibitory synapses in the
      dendritic tree differ between jaw-closing and -opening motoneurons.
AB  - This paper reviews recent data on the spatial distribution of inhibitory and
      excitatory synapses on the dendritic tree of jaw-closing (JC) and -opening (JO)
      motoneurons in the cat, in which a combination of techniques employing
      intracellular injections of horseradish peroxidase and postembedding immunogold
      labelling was used. The dendritic tree is divided into three segments: primary
      and distal dendrites and intermediate dendrites between the two segments. The
      proportion of inhibitory boutons (immunoreactive for GABA and/or glycine) is
      slightly higher than proportion of excitatory boutons (immunoreactive for
      glutamate) in JC motoneurons, but this trend is reversed in JO motoneurons. In
      the two kinds of motoneuron, boutons immunoreactive to glycine alone are more
      numerous than boutons double-labelled to GABA and glycine, which, in turn, occur
      more frequently than boutons immunoreactive to GABA alone. In JC motoneurons, the
      packing density (number of boutons per 100 microm(2)) of the inhibitory boutons
      decreases somatofugally, but this trend is not applicable to the excitatory
      boutons. In contrast, the packing density of the inhibitory and excitatory
      boutons in JO motoneurons does not significantly differ among the three dendritic
      compartments, though it is slightly higher for the excitatory than the inhibitory
      ones on each dendritic segment. These differences have important implications for
      synaptic integration in JC and JO motoneurons.

PMID- 17174265
TI  - CMT-3 inhibits orthodontic tooth displacement in the rat.
AB  - OBJECTIVE: Orthodontic tooth movement requires extensive remodeling of the
      periodontal ligament (PDL) and the alveolar bone. Osteoclasts resorb bone,
      allowing teeth to migrate in the direction of the force. Matrix
      metalloproteinases (MMPs) are able to degrade the extracellular matrix of the
      periodontal tissues. Chemically modified tetracyclines (CMTs) can inhibit MMPs,
      but lack antimicrobial activity. We hypothesize that CMT-3 will decrease the rate
      of orthodontic tooth movement in the rat. DESIGN: Eighteen Wistar rats received a
      standardized orthodontic appliance at one side of the maxilla. During 14 days,
      three groups of six rats received a daily dose of 0, 6 or 30mg/kg CMT-3, and
      tooth displacement was measured. Thereafter, osteoclasts were counted on
      histological sections using an ED-1 staining. Multi- and mononuclear ED-1
      positive cells in the PDL were also counted. In addition, sections were stained
      for MMP-9. RESULTS: CMT-3 significantly inhibited tooth movement (p=0.03) and
      also decreased the number of osteoclasts at the compression sides in the 30mg/kg
      group (p<0.05). Significantly more mono- than multinuclear ED-1-positive cells
      were present in the PDL, but no significant differences were found between the
      dosage groups. Osteoclasts in the 30mg/kg group seemed to contain less MMP-9 than
      in the control. CONCLUSIONS: CMT-3 inhibits tooth movement in the rat, probably
      by reducing the number of osteoclasts at the compression side. This might be due
      to induction of apoptosis in activated osteoclasts or reduced osteoclast
      migration. Reduced MMP activity by CMT-3 might also directly inhibit degradation
      of the organic bone matrix.

PMID- 17174267
TI  - Neuroplasticity of face primary motor cortex control of orofacial movements.
AB  - We have carried out a series of studies to address the role of the face primary
      motor area (MI) in the cerebral cortex in trained or semi-automatic orofacial
      motor behaviours and in behavioural adaptations to an altered oral environment.
      These studies have utilized intracortical microstimulation (ICMS), reversible
      cold block or single neurone recordings in face MI. Our studies in monkeys have
      revealed that face MI plays a strategic role in elemental and learned motor
      behaviours and in certain aspects of chewing and swallowing. Furthermore,
      successful training of awake monkeys in a novel tongue-protrusion task is
      associated with significant neuroplastic changes in face MI. These findings in
      monkeys are supported by correlated findings in humans which have revealed
      significantly enhanced corticomotoneuronal excitability when humans learn the
      novel tongue-protrusion task. Our related ICMS studies in rats reveal that
      trimming or extraction of the rat's lower incisors or damage to the rat's lingual
      nerve can result in significant changes in the MI representations of the tongue
      or jaw muscles. These various findings suggest that the face MI is important in
      orofacial motor skill acquisition and adaptation to an altered occlusion or loss
      of teeth or lingual sensory function, and that it reflects dynamic and modifiable
      constructs that are modelled by behaviourally significant experiences and that
      are critical to learning and adaptive processes.

PMID- 17174266
TI  - A novel mouse protein differentially regulated by androgens in the submandibular
      and lacrimal glands.
AB  - We characterized a cDNA clone derived from the female mouse submandibular gland
      (SMG). The transcript of this cDNA was approximately 1.2kb in size and predicted
      to code a 165-amino acid protein with a putative signal peptide for a secretory
      pathway. This protein, named submandibular androgen-repressed protein (SMARP),
      had homology in the N-terminal region with members of the glutamine/glutamic acid
      rich protein (GRP) family from rats. Northern blot analysis revealed that SMARP
      mRNA is expressed, out of the major mouse organs, only in the SMG and exorbital
      lacrimal gland (LG), with much more abundance in the former. For the SMG, the
      level of SMARP mRNA was 36 times higher in females than males, whereas for the LG
      it was 28 times higher in males than females. Furthermore, the level of SMARP
      mRNA was increased in the SMG but reduced in the LG with castration in males,
      whereas it was reduced in SMG but increased in LG after administration of
      testosterone in females or castrated males. In situ hybridization detected the
      signal for SMARP mRNA in the female SMG, and immunohistochemistry detected the
      signal for SMARP protein in the female SMG and male LG. In the female SMG, SMARP
      mRNA, and protein were localized intensively in a subpopulation of acinar cells,
      whereas in the male LG, SMARP protein was distributed diffusely in all acinar
      cells. These results suggested that SMARP is a secretory protein whose expression
      is regulated by androgens negatively in the SMG and positively in the LG.

PMID- 17174268
TI  - The variation in Fas localization and the changes in Fas expression level upon
      stimulation with growth factors.
AB  - Although Fas (APO-1/CD95) is well known as a death receptor, its stimulation
      occasionally fails to induce apoptosis in malignant cells. On the contrary, Fas
      is reported to advance the cell cycle in cancer cells. Therefore, we investigated
      roles of Fas in cell growth and apoptosis using human lung cancer cell lines. Fas
      was localized in the cytoplasm in exponentially growing cells, whereas only
      confluent cells expressed Fas on the cell membrane. A stimulation of confluent
      cells by either of EGF, IGF-I or VEGF induced once a decrease in Fas expression
      level and its sequential recovery. Fas expression levels in confluent cells were
      negatively correlated with cell doubling times (r=0.757, p=0.0088). Fas remained
      on the cell membrane of IgM-treated cells even after the growth factor
      stimulation, leading to apoptosis with abnormal mitosis, whereas the same
      stimulation induced Fas internalization in IgG(1)-treated cells. From these
      results, we suggest that Fas remaining on the cell membrane amplifies to induce
      apoptosis. Conversely, Fas internalization may enable cancer cells to escape from
      apoptosis. Our results suggest that growth factor may contribute to the
      resistance of cancer cells to Fas-mediated apoptosis in an autocrine or paracrine
      fashion.

PMID- 17174269
TI  - Emodin with PPARgamma ligand-binding activity promotes adipocyte differentiation
      and increases glucose uptake in 3T3-Ll cells.
AB  - Emodin, one of the main active components in the root and rhizome of Rheum
      palmatum L, promoted the conversion of 3T3-L1 fibroblasts to adipocytes, as
      evidenced by increased glycerol-3-phosphate dehydrogenase (GPDH) activity and the
      expression of adipocyte aP2 mRNA, as well as accelerated triacylglycerol (TG)
      accumulation, which was associated with increased mRNA expression levels of both
      C/EBPalpha and PPARgamma2. By using surface plasmon resonance (SPR) experiment,
      it was showed that emodin exhibited a very high binding affinity to PPARgamma. In
      differentiated 3T3-L1 adipocytes, emodin induced a time- and dose-dependent
      increase in glucose uptake as well as GLUT1 and GLUT4 mRNA expression, and the
      rate of uptake was partly abrogated by wortmannin (phosphoinositide 3-kinase
      inhibitor). Meanwhile, insulin-stimulated glucose uptake was increased
      significantly after treatment with low doses of emodin, and the degree of
      potentiation was decreased thereafter in response to increasing concentrations.
      Furthermore, 50 microM emodin profoundly inhibited insulin-stimulated glucose
      uptake by 25%. These data suggest a new role for emodin as a PPARgamma agonist in
      3T3-L1 cells. Besides, it is possible that emodin may also possess other
      properties contribute to glucose utilization in the adipocytes.

PMID- 17174270
TI  - Cellular prion protein in ovine milk.
AB  - Cellular prion protein, PrP(C), is essential for the development of prion
      diseases where it is considered to be a substrate for the formation of the
      disease-associated conformer, PrP(Sc). In sheep, PrP(C) is abundant in neuronal
      tissue and is also found at lower concentrations in a range of non-neuronal
      tissues, including mammary gland. Here, we demonstrate the presence of soluble
      PrP(C) in the non-cellular, non-lipid fraction of clarified ovine milk. Compared
      with brain-derived PrP(C), ovine milk PrP(C) displays an increased
      electrophoretic mobility. Ovine milk PrP(C) is mainly present as three species
      that differ in the extent of their N-linked glycosylation, with glycoform
      profiles varying among animals. Similar PrP(C) species are also present in fresh
      and commercial homogenised/pasteurised bovine milk, with additional N-terminal
      PrP(C) fragments detectable in ruminant milk and commercial milk products.

PMID- 17174271
TI  - Antimalarial properties of green tea.
AB  - We show here that a crude extract of green tea as well as two of its main
      constituents, epigallocatechin-3-gallate (EGCG) and epicatechin gallate (ECG),
      strongly inhibit Plasmodium falciparum growth in vitro. Both these catechins are
      found to potentiate the antimalarial effects of artemisinin without interfering
      with the folate pathway. The importance of these findings and their mechanistic
      implications are discussed in view of future therapeutic strategies.

PMID- 17174272
TI  - Circulating peripheral blood fibrocytes in human fibrotic interstitial lung
      disease.
AB  - Fibrotic interstitial lung diseases are illnesses of unknown cause characterized
      by progressive decline in lung function. Fibrocytes are bone marrow-derived,
      circulating progenitor cells capable of differentiating into diverse mesenchymal
      cell types. Prior work has shown fibrocytes to traffic to the lung via the CXCL12
      CXCR4 chemokine axis in an animal model of pulmonary fibrosis. We therefore
      assessed the relevance of fibrocytes in patients with fibrotic interstitial lung
      disease. We found enhanced expression of CXCL12 in both the lungs and plasma of
      patients with lung fibrosis. CXCL12 levels were associated with an order of
      magnitude higher number of circulating fibrocytes in the peripheral blood of
      these patients. Most of the circulating fibrocytes in patients with interstitial
      lung diseases were negative for the myofibroblast marker alpha-smooth muscle
      actin, suggesting a relatively undifferentiated phenotype. Taken together, these
      data suggest that fibrocytes are involved in the pathogenesis of human lung
      fibrosis.

PMID- 17174273
TI  - Antibodies to T-cell Ig and mucin domain-containing proteins (Tim)-1 and -3
      suppress the induction and progression of murine allergic conjunctivitis.
AB  - The T cell Ig and mucin domain-containing proteins (Tim) regulate Th1- and Th2
      mediated immune responses. We investigated the ability of Abs blocking Tim-1 or
      Tim-3 ligand-binding activity to prevent and treat murine experimental allergic
      conjunctivitis (EC), a Th2-mediated disease. Treatment with either Ab during the
      induction phase of EC in actively immunized wild-type mice suppressed EC and
      upregulated Th1 and Th2 immune responses. In contrast, both Abs exacerbated EC in
      actively immunized IFN-gamma-knockout mice. Thus, both anti-Tim Abs suppress the
      pathogenic immune responses generated in the induction phase by upregulating
      systemic IFN-gamma production. Treatment of actively immunized mice and passively
      immunized mice with either anti-Tim Ab just prior to RW challenge also suppressed
      EC. Thus, treatment with anti-Tim-1 or anti-Tim-3 Ab can suppress both the
      induction and progression of EC, which could indicate potential preventive and/or
      therapeutic approaches for allergic diseases such as allergic conjunctivitis.

PMID- 17174275
TI  - Involvement of integrins, MAPK, and NF-kappaB in regulation of the shear stress
      induced MMP-9 expression in endothelial cells.
AB  - Variations in the matrix metalloproteinase (MMP)-9 gene are related to the
      presence and severity of atherosclerosis. The aim of this study was to determine
      the signaling pathways of MMP-9 in endothelial cells subjected to low fluid shear
      stress. We found that low fluid shear stress significantly increased MMP-9
      expression, IkappaBalpha degradation, NF-kappaB DNA-binding activity and
      phosphorylation of MAPK in cultured human umbilical vein endothelial cells
      (HUVECs). Inhibition of NF-kappaB resulted in remarkable downregulation of stress
      induced MMP-9 expression. Pretreatment of HUVECs with inhibitors of p38 mitogen
      activating protein kinase (MAPK) and extracellular signal-regulated kinase1/2
      (ERK1/2) also led to significant suppression of stress-induced MMP-9 expression
      and NF-kappaB DNA-binding activity. Similarly, addition of integrins inhibitor to
      HUVECs suppressed the stress-induced MMP-9 expression, IkappaBalpha degradation,
      NF-kappaB DNA-binding activity and the phosphorylation of p38 MAPK, ERK1/2. Our
      findings demonstrated that the shear stress-induced MMP-9 expression involved
      integrins-p38 MAPK or ERK1/2-NF-kappaB signaling pathways.

PMID- 17174274
TI  - CD312, the human adhesion-GPCR EMR2, is differentially expressed during
      differentiation, maturation, and activation of myeloid cells.
AB  - EMR2/CD312 is a member of the adhesion-GPCR family that contains extracellular
      EGF-like domains. Previously it has been shown to interact with chondroitin
      sulphate glycosaminoglycans in an isoform-specific manner. Although EMR2
      expression has been found to be restricted to human myeloid cells, its expression
      profile has not yet been systemically characterized. In this report, we show that
      EMR2 receptor expression is up-regulated during differentiation and maturation of
      macrophages, and is conversely down-regulated during dendritic cell maturation.
      We also demonstrate that EMR2 receptor alternative splicing and glycosylation is
      regulated during myeloid differentiation. In monocytes and macrophages, EMR2 can
      be specifically up-regulated by LPS and IL-10 via an IL-10-mediated pathway. In
      inflamed tissues, EMR2 is detected in subpopulations of myeloid cells including
      macrophages and neutrophils. The results presented here further support the idea
      that EMR2 plays a role in the migration and adhesion of myeloid cells during cell
      differentiation, maturation, and activation.

PMID- 17174276
TI  - Proteomic expression analysis of cardiomyocytes subjected to proteasome
      inhibition.
AB  - We hypothesized that impaired proteasomal function affects gene expression in
      cardiomyocytes. To identify those genes, a proteomics-based analysis of neonatal
      rat cardiac myocytes treated with the proteasome inhibitor MG132 in comparison to
      vehicle treated control cells was performed. MG132 treatment induced reproducible
      changes in the protein expression profile, which was analyzed by two-dimensional
      difference gel electrophoresis followed by tryptic peptide mass fingerprinting
      for spot identification by MALDI-TOF mass spectrometry. The identified protein
      alterations could be grouped into three major categories: (1) induction of small
      heat shock proteins (HSPs) with chaperonic function, such as HSP27, alphaB
      crystallin, and cardiovascular HSP, (2) altered expression of actin associated
      proteins, such as cofilin-1 and transgelin, and (3) induction of antioxidant
      proteins, such as peroxiredoxin-1, superoxide dismutase-1, and hemeoxygenase-1.
      Northern blotting revealed that expression was regulated at the mRNA level. Given
      that proteasomal activity is decreased in cardiovascular diseases, alterations in
      proteasome-dependent control of mRNA expression could provide a novel mechanism
      by which disease progression is modulated.

PMID- 17174277
TI  - A novel approach for myocardial regeneration with educated cord blood cells
      cocultured with cells from brown adipose tissue.
AB  - Umbilical cord blood (CB) is a promising source for regeneration therapy in
      humans. Recently, it was shown that CB was a source of mesenchymal stem cells as
      well as hematopoietic stem cells, and further that the mesenchymal stem cells
      could differentiate into a number of cells types of mesenchymal lineage, such as
      cardiomyocytes (CMs), osteocytes, chondrocytes, and fat cells. Previously, we
      reported that brown adipose tissue derived cells (BATDCs) differentiated into CMs
      and these CMs could adapt functionally to repair regions of myocardial
      infarction. In this study, we examined whether CB mononuclear cells (CBMNCs)
      could effectively differentiate into CMs by coculturing them with BATDCs and
      determined which population among CBMNCs differentiated into CMs. The results
      show that BATDCs effectively induced CBMNCs that were non-hematopoietic stem
      cells (HSCs) (educated CB cells: e-CBCs) into CMs in vitro. E-CBCs reconstituted
      infarcted myocardium more effectively than non-educated CBMNCs or CD34-positive
      HSCs. Moreover, we found that e-CBCs after 3 days coculturing with BATDCs induced
      the most effective regeneration for impaired CMs. This suggests that e-CBCs have
      a high potential to differentiate into CMs and that adequate timing of
      transplantation supports a high efficiency for CM regeneration. This strategy
      might be a promising therapy for human cardiac disease.

PMID- 17174278
TI  - Sentence comprehension and action: effector specific modulation of the motor
      system.
AB  - The purpose of the paper is to study whether sentence comprehension modulates the
      motor system. Participants were presented with 24 pairs of nouns and verbs that
      could be referred to hand and mouth actions (e.g., to unwrap vs. to suck the
      sweet), in the first block, or, in the second block, to 24 hand and foot actions
      (e.g., to throw vs. kick the ball). An equal number of non-sensible pairs were
      presented. Participants' task consisted of deciding whether the combination made
      sense or not: 20 participants responded by saying yes loudly into a microphone,
      20 by pressing a pedal. Results support embodied theories of language
      comprehension, as they suggest that sentence processing activates an action
      simulation. This simulation is quite detailed, as it is sensitive to the effector
      involved. Namely, it leads to a facilitation in responses to 'mouth sentences'
      and 'foot sentences' compared to 'hand sentences' in case of congruency between
      the effectors - mouth and foot - involved in the motor response and in the
      sentence.

PMID- 17174279
TI  - Differential regulation of the tyrosine hydroxylase and enkephalin neuropeptide
      transmitter genes in rat PC12 cells by short chain fatty acids: concentration
      dependent effects on transcription and RNA stability.
AB  - At physiologic concentrations, butyrate regulates the expression of individual
      genes involving at least three mechanisms: (i) through induction of cis- and
      trans-acting butyrate-dependent transcription factors for selected genes, (ii) by
      inhibition of histone deacetylation and attendant chromatin remodeling and (iii)
      by affecting turnover of mRNAs. Our previous work illustrated gradual
      accumulation of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in
      catecholamine biosynthesis and the neuropeptide transmitter proenkephalin (ppEnk)
      in butyrate-differentiated PC12 cells (Nankova, B.B., Chua, J., Mishra, R.,
      Kobasiuk, C.D., La Gamma, E.F. 2003. Nicotinic induction of preproenkephalin and
      tyrosine hydroxylase gene expression in butyrate-differentiated rat PC12 cells: a
      model for adaptation to gut-derived environmental signals. Pediatr. Res. 53, 113
      118.). However, at higher physiological concentrations (6 mM), TH mRNA levels are
      significantly reduced while ppEnk mRNA transcripts remained elevated. These
      differential effects suggest suppression of endogenous TH gene transcription,
      targeted degradation of TH mRNA or both. By using nuclear run-on assays, we found
      that transcription increased for both endogenous TH and ppEnk genes, even at time
      points and concentrations when reduced steady-state levels of TH mRNA were
      observed. The reduction in TH mRNA was blocked by cycloheximide consistent with a
      protein-dependent mechanism. We also observed a dose-dependent accumulation of
      luciferase reporter molecules driven by TH promoter in transient transfection
      experiments, data that provide additional support for separate regulatory
      pathways. Significantly, butyrate-dependent decreases in TH mRNA were also
      reflected in a reduction in TH protein. Our results suggest a novel mode of
      regulation for TH by butyrate operating via both transcriptional and post
      transcriptional mechanisms. We speculate that, depending on plasma concentrations
      of butyrate, this naturally occurring signaling molecule can function as an in
      vivo molecular switch to alter levels of TH mRNA, its protein and thus the
      biosynthesis of endogenous catecholamines.

PMID- 17174280
TI  - Apoptotic changes in the cortex and hippocampus following minimal brain trauma in
      mice.
AB  - Interpretation of the cellular and molecular pathogenic basis of post-minimal
      traumatic brain injury is a significant clinical and scientific problem,
      especially due to the high prevalence of motor vehicle--and other accidents.
      Pathogenetic brain mechanisms following traumatic impact are usually investigated
      by using models of severe or moderate trauma. Apoptotic neuronal degeneration
      after notable brain trauma is a well-known phenomenon, but the source of its
      activation is not clear, especially after mild, subclinical brain trauma. In the
      present study, we used a closed head weight-drop model to induce minimal brain
      injury in mice. Pellets of 5, 10, 15, 20, 25 and 30 g were dropped on the right
      side of mice's head kept under light ether anesthesia. No abnormal behavioral or
      neurophysiological changes were seen following the head trauma. Morphological
      assessment was done 72 h after the traumatic impact using TUNEL assay and silver
      staining. We found gradual increase of TUNEL-positive and silver-impregnated
      cells number in different cortical and hippocampal regions of both injured and
      contralateral hemispheres. The threshold of traumatic impact that caused a
      significant activation was 10-15 g pellets (evident by silver staining), and 15
      20 g for apoptosis. The most sensitive zones for trauma were anterior cingulate
      cortex and CA3 area of hippocampus. No bilateral hemispheric differences were
      found. Our results demonstrate that even closed head minimal traumatic brain
      injury can cause diffused neuronal damage and apoptosis. This results correlate
      well with cognitive and behavioral deficits described for mice suffering similar
      mTBI and can also explain the wide variety of mental disturbances described for
      post-concussion syndrome in patients who suffered mild head injury.

PMID- 17174282
TI  - Prenatal carbocyanine dye tracing of septo-hypothalamic connections.
AB  - This is the first study of the prenatal development of septal projections to the
      hypothalamus in rats, using carbocyanine dyes (DiI and DiA) as retrograde
      tracers. First septal neurons send axons to the preoptic area and anterior
      hypothalamus on embryonic day 14,5 (E14,5) and on E15 numerous labeled neurons
      are visualized in the septum after DiI insertion into the preoptic region. On E18
      and E20 these neurons develop numerous spiny dendrites that occupy all
      rostrocaudal extension of the septum with concentration in the ventral part of
      the septum. Only a few septal neurons send their axons to the mediobasal
      hypothalamus at E15 confirmed by double-labeling (DiI+DiA) experiments on E20
      E21. All septo-hypothalamic connections are unilateral and the number of the
      neurons revealed in the septum correlates with the place and size of the DiI
      insertion in the hypothalamus: more lateral and anterior hypothalamic marker
      insertions always resulted in significant neuronal labeling in the septum. No
      septal connections with the posterior hypothalamus specifically, the mammillary
      bodies are formed prenatally. We have demonstrated that the development of septal
      projections to various rostrocaudal regions of the hypothalamus take place during
      different stages of development. Prominent parts of the septal projections are to
      the preoptic area and anterior hypothalamus while few connections with the
      mediobasal hypothalamus are formed prenatally. These data provide basic knowledge
      of early steps of the development of the septo-hypothalamic connections.

PMID- 17174281
TI  - Lipopolysaccharide impairs long-term potentiation and recognition memory and
      increases p75NTR expression in the rat dentate gyrus.
AB  - The role of the neurotrophins, including nerve growth factor, in synaptic
      plasticity is well established. These proteins exert their effects via activation
      of Trk receptor tyrosine kinases and the p75 neurotrophin receptor (p75NTR).
      While Trk receptor activation is associated with functions such as cell survival,
      learning and enhancement of synaptic transmission, p75NTR can modulate long-term
      depression and has been reported to be a regulator of apoptosis. Peripheral
      administration of lipopolysaccharide (LPS) has been shown to exert a number of
      effects centrally, including inhibition of hippocampal synaptic plasticity. Here
      we report that LPS induces a blockade of long-term potentiation and recognition
      memory that is concomitant with increased expression of the p75NTR in dentate
      gyrus. In addition, LPS blocks plasticity-associated changes in nerve growth
      factor expression, TrkA activation and extracellular signal-regulated kinase
      activation. These data are consistent with the hypothesis that synaptic
      plasticity in the dentate gyrus is associated with changes in neurotrophin
      signaling and that the inhibition of these plastic changes by LPS may be due in
      part to its ability to impact on these signaling cascades.

PMID- 17174283
TI  - Cocaine- and amphetamine-regulated transcript (CART) expression is differentially
      regulated in the hypothalamic paraventricular nucleus of lactating rats exposed
      to suckling or cold stimulation.
AB  - Neural stimuli, such as suckling or cold exposure, increase TRH mRNA in the
      paraventricular nucleus (PVN) of the rat hypothalamus, yet only suckling induces
      prolactin secretion. As TRH co-localizes with cocaine- and amphetamine-regulated
      transcript (CART) in hypophysiotropic neurons of the PVN, and CART inhibits TRH
      induced prolactin release but not TRH-induced TSH release in adenohypophyseal
      cell cultures, we raised the possibility that differential regulation of CART
      gene expression in the PVN may explain the differences in prolactin secretion
      following each of the two stimuli. Primiparous female rats were mated and handled
      daily during the pre- and postpartum periods. After delivery, the litter was
      adjusted to 8 pups and at mid-lactation, dams were separated from their pups for
      8 h and exposed to either 1 h of cold or 30 min of suckling. Long-term effects of
      suckling were studied by separating pups from their mothers for 24 h, followed by
      a 12 h period of continuous suckling. Serum TSH levels increased in response to
      cold exposure, while prolactin levels were increased by suckling and diminished
      by cold exposure. CART mRNA levels increased in rostral and mid parts of the
      medial parvocellular PVN following cold exposure but not after suckling
      stimulation. These data demonstrate a differential regulation of CART gene
      expression in hypophysiotropic neurons in response to stimuli that increase TRH
      mRNA levels, and suggest that CART activation in the PVN may contribute to the
      decrease in PRL release when the thyroid axis is activated by cold exposure.

PMID- 17174284
TI  - What determines sustained visual attention? The impact of distracter positions,
      task difficulty and visual fields compared.
AB  - We quantified the interference of distracter stimuli on sustained visuo-spatial
      attention as a function of the distribution of attended positions in the visual
      fields (bilateral/unilateral, left/right, upper/lower), distracter positions
      (peripheral, between attended positions, between fixation and attended positions)
      and task difficulty. Compared to distinct distracter positions, bilateral field
      and lower field presentation had much stronger influence on the performance.
      Additionally, interactive effects between task difficulty and distracter position
      were found. This result was at variance with the previous models of visuo-spatial
      attention, which attached much more importance to the role of distracter
      positions compared to visual field effects. In directly comparing the impact of
      the abovementioned factors, the converse finding is evident-visual field effects,
      in particular bilateral presentations have a much stronger importance. Moreover,
      metaphoric concepts of attention like the "zoom lens" are not compatible with
      these results. The findings are discussed in the light of alternative models of
      sustained visuo-spatial attention. The visual system architecture and top-down
      mechanisms are considered.

PMID- 17174286
TI  - Effects of (-)-epigallocatechin-3-gallate on the activity of substantia nigra
      dopaminergic neurons.
AB  - Despite many studies on the biological and pharmacological properties of (-)
      epigallocatechin-3-gallate (EGCG), an active component of green tea, information
      on neuronal modulation by EGCG is limited. This study was designed to investigate
      the effects of EGCG on the electrical activity of rat substantia nigra
      dopaminergic neurons using whole-cell patch clamp recordings. The spike frequency
      was increased to 6.33+/-0.23 (p<0.05) and 7.15+/-0.29 (p<0.05) by 5 and 10 microM
      EGCG, respectively, from the control level of 5.49+/-0.19 spikes/second,
      respectively (n=18). The resting membrane potential of the cells was decreased to
      -45.66+/-0.45 and -43.99+/-0.87 (p<0.05), by 5 and 10 microM EGCG, respectively,
      from -47.82+/-0.57 mV. The amplitude of afterhyperpolarization was decreased to
      12.73+/-0.45 (p<0.05) and 11.60+/-0.57 (p<0.05) by 5 and 10 microM EGCG,
      respectively, from 13.80+/-0.31 mV. The neuronal activity of dopaminergic neurons
      is closely linked to dopamine release. When neurons switch from a single-spike
      firing to bursts of action potentials, the release of dopamine increases. The
      above experimental results suggest that EGCG increases the neuronal activity via
      inhibition of calcium-dependent potassium currents underlying the
      afterhyperpolarization, and it could act as a facilitating factor that elicits
      NMDA-dependent bursts of action potentials like apamin or bicuculline methiodide.

PMID- 17174285
TI  - Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N
      SH cells.
AB  - Oxidative stress is implicated in neurodegenerative diseases including stroke,
      Alzheimer's disease and Parkinson's disease, and has been extensively studied as
      a potential target for therapeutic intervention. Pyruvate, a natural metabolic
      intermediate and energy substrate, exerts antioxidant effects in brain and other
      tissues susceptible to oxidative stress. We tested the protective effects of
      pyruvate on hydrogen peroxide (H(2)O(2)) toxicity in human neuroblastoma SK-N-SH
      cells and the mechanisms underlying its protection. Hydrogen peroxide insult
      resulted in 85% cell death, but co-treatment with pyruvate dose-dependently
      attenuated cell death. At concentrations of >or=1 mM, pyruvate totally blocked
      the cytotoxic effects of H(2)O(2). Pyruvate exerted its protective effects even
      when its administration was delayed up to 2 h after H(2)O(2) insult. As a
      scavenger of reactive oxygen species (ROS), pyruvate dose-dependently attenuated
      H(2)O(2)-induced ROS formation, assessed from 2,7-dichlorofluorescein diacetate
      fluorescence. Furthermore, pyruvate suppressed superoxide production by
      submitochondrial particles, and attenuated oxidative stress-induced collapse of
      the mitochondrial membrane potential. Collectively, these results suggest that
      pyruvate protects neuronal cells through its antioxidant actions on mitochondria.

PMID- 17174287
TI  - Impulsivity-anxiety-related behavior and profiles of morphine-induced analgesia
      in heterozygous reeler mice.
AB  - Reelin is an extracellular matrix protein, secreted by GABAergic interneurons,
      that provides a signal for neural plasticity. A downregulation of reelin may be a
      factor to be considered in the study of major psychiatric disorders. The
      heterozygous reeler mouse model, thus, may be important to reveal those
      alterations in behavioral phenotype produced by reduced neural plasticity.
      Heterozygous (HZ) and wild-type (WT) mice were tested for anxiety-related
      behavior, motor impulsivity, and morphine-induced analgesia. Heterozygous mice
      showed significantly lower levels of anxiety- and risk-assessment-related
      behaviors in the elevated plus-maze during adolescence, in the absence of basal
      changes in general locomotion. Adult mice were assessed for profiles of impulsive
      behavior in operant chambers, and HZ mice exhibited elevated levels of motor
      impulsivity. When mice were assessed in nociception tests, a genotype difference
      in morphine-induced analgesia was found, and these results were confirmed by
      measurement of mu-receptors in the midbrain. The basal behavioral profile of the
      HZ genotype reveals important differences, consistent with decreased behavioral
      inhibition and emotionality, which can be revealed as early as in adolescence,
      together with slight increment of impulsive behavior and altered pain threshold
      and at the adult age. The HZ genotype can thus represent a useful animal model
      for the study of behavioral disorders consequent to reduced neural plasticity.

PMID- 17174288
TI  - The role of angiotensin receptor-1 blockade on electromechanical changes induced
      by left ventricular hypertrophy and its regression.
AB  - OBJECTIVE: The aims of this study were to: i) investigate the role of angiotensin
      in mediating changes to myocardial electromechanical properties during the
      development and regression of left ventricular hypertrophy (LVH) generated by
      constriction of the thoracic aorta; ii) identify any role of angiotensin-1
      receptor blockade on ameliorating changes to these electromechanical properties.
      METHODS: LVH was induced in guinea-pigs by constricting the ascending aorta (AC
      groups). After 42+/-3 days, the constriction was either removed or left in place.
      Following the second operation animals were fed losartan (10 mg x kg(-1) x day(
      1)) or saline for 42+/-3 days. Sham-operated animals served as controls. In other
      groups, LVH was generated by subcutaneous angiotensin II (200 ng x kg(-1) x min(
      1)) infusion for 42+/-3 days with or without losartan administration (AT groups),
      and compared to animals undergoing aortic constriction for a similar period.
      Electromechanical changes were recorded in isolated left ventricular myocardial
      preparations. RESULTS: Wet and dry heart-to-body weight ratios (HBR) increased
      significantly in the AC and AT models compared to control. Losartan prevented the
      increase of HBR in the AT group. Removal of the constriction allowed LVH to
      regress to control. The force-frequency relationship was reduced in both models
      and recovered fully on regression. However, the two models generated different
      electrophysiological changes: in the AC group, longitudinal conduction velocity
      was reduced and transverse conduction increased, with a consequent reduction of
      the anisotropic conduction ratio. On regression recovery was only partial; action
      potential duration was prolonged and did not recover. In the AT group,
      electrophysiological changes were limited: only an increase of transverse
      conduction and a reduction of the anisotropic conduction ratio were observed.
      Losartan had no effect on HBR or electromechanical variables in the aortic
      constricted animals, nor did it affect the extent of recovery in animals with
      regression of LVH. CONCLUSIONS: The electromechanical changes to hypertrophied
      myocardium are different in these two models of LVH. Moreover, losartan was
      ineffective in modulating the consequences of hypertrophy induced by constriction
      of the thoracic aorta.

PMID- 17174289
TI  - Glyco- and sphingophosphonolipids from the medusa Phyllorhiza punctata: NMR and
      ESI-MS/MS fingerprints.
AB  - The medusa Phyllorhiza punctata has been found in Brazilian waters where it is an
      exotic species, having arrived in ballasts from the Indo-Pacific Ocean in the
      general region of North Australia and Indonesia. Fatty acids of the intact animal
      and its component umbrella, oral arms, and mucus were identified. Two different
      groups of glycolipids and a sphingolipid were isolated by silica-gel column
      chromatography and characterized using GC-MS, ESI-MS, 1D, 2D (13)C, (1)H and
      (31)P NMR spectroscopy. They were sulfoquinovosyldiacylglycerol (SQDG),
      monogalactosyldiacylglycerol (MGDG), and ceramide aminoethylphosphonate (CAEP).
      The CAEP long chain base (LCB) and its polar head group (PHG) formed by partial
      hydrolysis, were analyzed by ESI-MS/MS. The probable origin of MGDG and SQDG in
      the jellyfish is the result of an endosymbiotic association with a microalga of
      the Dinoflagellate group, since these lipids are commonly found in photosynthetic
      membranes.

PMID- 17174290
TI  - Specificity assessment of immunoassay kits for determination of urinary free
      cortisol concentrations.
AB  - BACKGROUND: In immunoassay kits for determination of urinary free cortisol (UFC)
      concentrations, the results vary markedly from kit to kit, so we compared in this
      study the reaction specificity among 4 commercially available immunoassay kits to
      determine the applicability of these assays in routine determination of UFC
      concentrations. METHOD: Using 4 commercially available kits, cross-reaction was
      investigated. In addition, urine samples were fractionated by HPLC to investigate
      endogenous immunoreactive cortisol responses. HPLC fractions were subjected to
      gas chromatography-mass spectrometry (GCMS) to identify substances causing inter
      kit assay discrepancies. RESULTS: Among the 4 kits, cortisol Kit "TFB"
      (Immunotech; IOT-RIA method) showed the lowest cross-reaction (2.5%) for
      prednisolone. Furthermore, on HPLC, 87.8% of the reaction of the entire fraction
      was seen in the fractions corresponding to the elution position of standard
      cortisol with the IOT-RIA method; this was the highest percentage among the 4
      kits. GCMS revealed that the substance that showed a cross-reaction with the
      other 3 kits was 5alpha-tetrahydrocortisol (5alpha-THF) glucuronide. CONCLUSIONS:
      The IOT-RIA method was found to be the most specific for UFC. The other 3
      commercially available kits showed cross-reaction with a conjugate of 5alpha-THF,
      found to be one of the causes of inter-kit assay discrepancies.

PMID- 17174292
TI  - Attentional modulation of masked repetition and categorical priming in young and
      older adults.
AB  - Three experiments examined the effects of temporal attention and aging on masked
      repetition and categorical priming for numbers and words. Participants' temporal
      attention was manipulated by varying the stimulus onset asynchrony (i.e.,
      constant or variable SOA). In Experiment 1, participants performed a parity
      judgment task and a lexical decision task in which categorical priming and
      repetition priming were, respectively, tested. Experiment 2 used a semantic
      categorization task testing categorical priming. In Experiment 3, repetition and
      categorical priming were tested in the same semantic categorization task with the
      same stimuli. The results of the three experiments showed that masked repetition
      priming is insensitive to manipulations of temporal attention whereas categorical
      priming is. Furthermore, no differences were found between young and older adults
      in repetition priming effects, again contrasting with the categorical priming
      results for which older adults were more sensitive to attentional manipulations
      than young adults.

PMID- 17174291
TI  - Establishment and evaluation of 2 monoclonal antibodies against oxidized
      apolipoprotein A-I (apoA-I) and its application to determine blood oxidized apoA
      I levels.
AB  - BACKGROUND: Apolipoprotein A-I (apoA-I) is the major lipoprotein component of
      high-density lipoprotein(HDL), and plays an important role in reverse cholesterol
      transport. Its function is known to be influenced by oxidation. METHODS: Using
      H2O2-or chloramine T-oxidized apoA-I as antigen, we prepared 2 kinds of
      monoclonal antibodies, and established an ELISA system for the measurement of
      oxidized apoA-I. RESULTS: The 2 monoclonal antibodies obtained, 7D3 and 98A7,
      exhibited different reactivity characteristics. The serum level of oxidized apoA
      I was higher in patients with either inflammatory disease or diabetes than in
      healthy individuals, and suggested a diversity of oxidized apoA-I. CONCLUSION:
      The 2 monoclonal antibodies are useful for the determination of oxidized apoA-I
      and study of diverse oxidized HDLs.

PMID- 17174293
TI  - Effects of cryopreservation methods on post-thaw motility of spermatozoa from the
      Japanese pearl oyster, Pinctada fucata martensii.
AB  - In order to develop cryopreservation techniques for Japanese pearl oyster
      spermatozoa, the effects of various cryopreservation conditions on post-thaw
      motility were examined. Spermatozoa cryopreserved with 10% methanol (MET),
      dimethylformamide or dimethylacetamide plus 90% diluent comprising 80% seawater
      and 20% fetal bovine serum (FBS) showed higher percentages of post-thaw motility
      than those cryopreserved with 10% dimethylsulfoxide or glycerol. When spermatozoa
      were cryopreserved with various concentrations (0-20%) of MET and 100-80%
      diluent, 10% MET showed the highest percentages of post-thaw motility. When
      spermatozoa were cryopreserved with 10% MET and 90% diluent comprising various
      concentrations (0-100%) of FBS or Ringer solution mixed with seawater, the
      percentages of post-thaw motility peaked at 20% FBS or Ringer solution, and were
      significantly higher for 20% FBS than for 20% Ringer solution. The percentages of
      post-thaw motility increased with increasing dilution ratios from 2.5- to 50
      fold. Spermatozoa cooled to -50 degrees C and then immersed in liquid nitrogen
      (LN) showed higher post-thaw motility than those cooled to -30 degrees C or -40
      degrees C. When spermatozoa were cryopreserved to -50 degrees C at various
      cooling rates by changing the sample height above the LN surface, the post-thaw
      motilities of spermatozoa cooled at 10 cm (cooling rate: -21.3 degrees C/min) and
      12.5 cm (-15.6 degrees C/min) from the LN surface were higher than those at 5,
      7.5 or 15 cm. These results indicate that 10% MET plus 90% diluent comprising 80%
      seawater and 20% FBS is a suitable extender for cryopreservation of Japanese
      pearl oyster spermatozoa and that samples should be cooled to -50 degrees C at a
      cooling rate between -15 and -20 degrees C/min for efficient storage.

PMID- 17174294
TI  - Apoptosis in early development of the sea urchin, Strongylocentrotus purpuratus.
AB  - Apoptosis provides metazoans remarkable developmental flexibility by (1)
      eliminating damaged undifferentiated cells early in development and then (2)
      sculpting, patterning, and restructuring tissues during successive stages
      thereafter. We show here that apoptotic programmed cell death is infrequent and
      not obligatory during early embryogenesis of the purple sea urchin,
      Strongylocentrotus purpuratus. During the first 30 h of urchin development, fewer
      than 20% of embryos exhibit any cell death. Cell death during the cleavage stages
      consists of necrotic or pathological cell death, while cell death during the
      blastula and gastrula stages is random and predominantly caspase-mediated
      apoptosis. Apoptosis remains infrequent during the late blastula stage followed
      by a gradual increase in frequency during gastrulation. Even after prolonged
      exposure during the cleavage period to chemical stress, apoptosis occurs in less
      than 50% of embryos and always around the pre-hatching stage. Embryonic
      suppression of apoptosis through caspase inhibition leads to functionally normal
      larvae that can survive to metamorphosis, but in the presence of inducers of
      apoptosis, caspase inhibition leads to deformed larvae and reduced survival.
      Remarkably, however, pharmacological induction of apoptosis, while reducing
      overall survival, also significantly accelerates development of the survivors
      such that metamorphosis occurs up to a week before controls.

PMID- 17174295
TI  - A novel gene, BENI is required for the convergent extension during Xenopus laevis
      gastrulation.
AB  - Activin-like signaling plays an important role in early embryogenesis. Activin A,
      a TGF-beta family protein, induces mesodermal/endodermal tissues in animal cap
      assays. In a screen for genes expressed early after treatment with activin A, we
      isolated a novel gene, denoted as BENI (Brachyury Expression Nuclear Inhibitor).
      The BENI protein has a conserved domain at the N-terminus that contains a nuclear
      localization signal (NLS), and two other NLSs in the C-terminal domain. BENI mRNA
      was localized to the animal hemisphere at the gastrula stages and to ectoderm
      except for neural regions at stage 17; expression persisted until the tadpole
      stage. The overexpression of BENI caused gastrulation defects and inhibition of
      elongation of activin-treated animal caps with reduction of Xbra expression.
      Moreover, whole-mount in situ hybridization revealed reduced expression of Xbra
      in BENI mRNA-injected regions of gastrula embryos. Functional knockdown of BENI
      using an antisense morpholino oligonucleotide also resulted in an abnormal
      phenotype of embryos curling to the dorsal side, and excessive elongation of
      activin-treated animal caps without altered expression of mesodermal markers.
      These results suggested that BENI expression is regulated by activin-like
      signaling, and that this regulation is crucial for Xbra expression.

PMID- 17174296
TI  - Contributions of extracellular and intracellular Ca2+ to regulation of sperm
      motility: Release of intracellular stores can hyperactivate CatSper1 and CatSper2
      null sperm.
AB  - In order to fertilize, mammalian sperm must hyperactivate. Hyperactivation is
      triggered by increased flagellar Ca(2+), which switches flagellar beating from a
      symmetrical to an asymmetrical pattern by increasing bending to one side.
      Thimerosal, which releases Ca(2+) from internal stores, induced hyperactivation
      in mouse sperm within seconds, even when extracellular Ca(2+) was buffered with
      BAPTA to approximately 30 nM. In sperm from CatSper1 or CatSper2 null mice, which
      lack functional flagellar alkaline-activated calcium currents, 50 microM
      thimerosal raised the flagellar bend amplitudes from abnormally low levels to
      normal pre-hyperactivated levels and, in 20-40% of sperm, induced
      hyperactivation. Addition of 1 mM Ni(2+) diminished the response. This suggests
      that intracellular Ca(2+) is abnormally low in the null sperm flagella. When
      intracellular Ca(2+) was reduced by BAPTA-AM in wild-type sperm, they exhibited
      flagellar beat patterns more closely resembling those of null sperm. Altogether,
      these results indicate that extracellular Ca(2+) is required to supplement store
      released Ca(2+) to produce maximal and sustained hyperactivation and that
      CatSper1 and CatSper2 are key elements of the major Ca(2+) entry pathways that
      support not only hyperactivated motility but possibly also normal pre
      hyperactivated motility.

PMID- 17174298
TI  - Ticlopidine attenuates progression of atherosclerosis in apolipoprotein E and low
      density lipoprotein receptor double knockout mice.
AB  - Platelets are involved in the development of atherothrombosis. However, the anti
      atherosclerotic effects of thienopiridines have not been, as yet, proven. We
      analyzed the effects of ticlopidine on atherogenesis in apolipoprotein E/low
      density lipoprotein receptor double knockout (apoE/LDLR(-/-)) mice. 2-month-old
      apoE/LDLR(-/-) mice fed a Western diet (21% fat, 0.15% cholesterol) were treated
      with ticlopidine (90 mg/kg/day) for a period of 4 months. In 6-month-old
      apoE/LDLR(-/-) mice treated with ticlopidine and in their non-treated
      counterparts we analyzed: cholesterol and triglyceride levels, the size of
      atherosclerotic plaques in aortic roots (oil red-O staining, cross-section
      method), and in the whole aorta (Sudan IV staining, en face method), the number
      of macrophages in atherosclerotic plaque (CD68 staining), as well as the
      endothelial function in the isolated thoracic aorta. Concentrations of total
      cholesterol and triglycerides in plasma were not altered by treatment with
      ticlopidine. However, the size of atherosclerotic plaques measured in aortic
      roots by the cross-section method and the number of macrophages estimated by anti
      CD68 staining were significantly reduced by ticlopidine treatment. In contrast,
      the effect of ticlopidine on the area covered by plaques in the whole aorta (en
      face analysis) was not statistically significant. Importantly, acetylcholine
      induced vasodilation in isolated aorta was improved in ticlopidine-treated
      apoE/LDLR(-/-) mice as compared to their non-treated counterparts. In conclusion,
      ticlopidine attenuates the progression of atherosclerosis and improves the
      endothelial function in apoE/LDLR(-/-) mice.

PMID- 17174297
TI  - The UBX-regulated network in the haltere imaginal disc of D. melanogaster.
AB  - Hox proteins have been proposed to act at multiple levels within regulatory
      hierarchies and to directly control the expression of a plethora of target genes.
      However, for any specific Hox protein or tissue, very few direct in vivo
      regulated target genes have been identified. Here, we have identified target
      genes of the Hox protein Ultrabithorax (UBX), which modifies the genetic
      regulatory network of the wing to generate the haltere, a modified hindwing. We
      used whole-genome microarrays and custom arrays including all predicted
      transcription factors and signaling molecules in the Drosophila melanogaster
      genome to identify differentially expressed genes in wing and haltere imaginal
      discs. To elucidate the regulation of selected genes in more detail, we isolated
      cis-regulatory elements (CREs) for genes that were specifically expressed in
      either the wing disc or haltere disc. We demonstrate that UBX binds directly to
      sites in one element, and these sites are critical for activation in the haltere
      disc. These results indicate that haltere and metathoracic segment morphology is
      not achieved merely by turning off the wing and mesothoracic development
      programs, but rather specific genes must also be activated to form these
      structures. The evolution of haltere morphology involved changes in UBX-regulated
      target genes, both positive and negative, throughout the wing genetic regulatory
      network.

PMID- 17174299
TI  - Decreased [3H] YM-09151-2 binding to dopamine D2 receptors in the hypothalamus,
      brainstem and pancreatic islets of streptozotocin-induced diabetic rats.
AB  - In the present study dopamine was measured in the hypothalamus, brainstem,
      pancreatic islets and plasma, using HPLC. Dopamine D2 receptor changes in the
      hypothalamus, brainstem and pancreatic islets were studied using [3H] YM-09151-2
      in streptozotocin-induced diabetic and insulin-treated diabetic rats. There was a
      significant decrease in dopamine content in the hypothalamus (P<0.001), brainstem
      (P<0.001), pancreatic islets (P<0.001) and plasma (P<0.001) in diabetic rats when
      compared to control. Scatchard analysis of [3H] YM-09151-2 in the hypothalamus of
      diabetic rats showed a significant decrease in Bmax (P<0.001) and Kd, showing an
      increased affinity of D2 receptors when compared to control. Insulin treatment
      did not completely reverse the changes that occurred during diabetes. There was a
      significant decrease in Bmax (P<0.01) with decreased affinity in the brainstem of
      diabetic rats. The islet membrane preparation of diabetic rats showed a
      significant decrease (P<0.001) in the binding of [3H] YM-09151-2 with decreased
      Kd (P<0.001) compared to control. The increase in affinity of D2 receptors in
      hypothalamus and pancreatic islets and the decreased affinity in brainstem were
      confirmed by competition analysis. Thus our results suggest that the decreased
      dopamine D2 receptor function in the hypothalamus, brainstem and pancreas affects
      insulin secretion in diabetic rats, which has immense clinical relevance to the
      management of diabetes.

PMID- 17174300
TI  - Subchronic nicotine exposure in adolescence induces long-term effects on
      hippocampal and striatal cannabinoid-CB1 and mu-opioid receptors in rats.
AB  - There is evidence for the existence of functional interactions between nicotine
      and cannabinoids and opioid compounds in adult experimental animals. However,
      there is scarce information about these relationships in young animals. In the
      present study we evaluated short and long-term effects of a subchronic nicotine
      treatment [0.4 mg/kg daily i.p. injections from postnatal day (PND) 34 to PND
      43], upon hippocampal and striatal cannabinoid-CB(1) and mu-opioid receptors in
      Wistar rats of both genders. Rats were sacrificed 2 h after the last nicotine
      injection (short-term effects, PND 43) or one month later (long-term effects, PND
      75). Hippocampal and striatal cannabinoid CB(1) and mu-opioid receptors were
      quantified by Western blotting. The subchronic nicotine treatment induced a
      region-dependent long-lasting effect in cannabinoid CB(1) receptor: a significant
      increase in hippocampal cannabinoid CB(1) receptors and a significant decrease in
      striatal cannabinoid CB(1) receptors, with these effects being similar in males
      and females. With respect to mu-opioid receptors, subchronic nicotine induced a
      significant down-regulation in hippocampal and striatal mu-opioid receptors in
      the long-term, and within the striatum the effects were more marked in adult
      males than in females. The present results indicate that juvenile nicotine taking
      may have implications for the endocannabinoid and endogenous opioid function and
      for the behaviors served by those systems, this includes possible modification of
      the response of adults to different psychotropic drugs, i.e. cannabis and
      morphine/heroin when taken later in life.

PMID- 17174301
TI  - Muscarinic M2 receptor is active on pancreatic islets from hypothalamic obese
      rat.
AB  - Hypothalamic obese rats, obtained by neonatal treatment with monosodium L
      glutamate (MSG), are hyperinsulinemic, and secrete more insulin than lean ones do
      when stimulated by glucose, while acetylcholine insulinotropic effect decreases.
      The effect of acetylcholine on glucose-induced insulin secretion is attributed to
      muscarinic receptors of pancreatic beta cells, mainly to M(3) subtype. However,
      it has been observed that activation of M(2) or M(4) subtypes causes inhibition
      of glucose-induced insulin secretion in insulin secreting cell line. Insulin
      secretion was measured, stimulated by glucose in the presence of acetylcholine
      plus methoctramine, a muscarinic M(2) antagonist, on pancreatic islets isolated
      from MSG-obese and lean rats to investigate whether impairment of acetylcholine
      insulinotropic effect on pancreatic islets from MSG-obese rats has any
      relationship with muscarinic M(2) receptor function in beta cells. Insulin
      secretion stimulated by 8.3 mM glucose was higher in islets from obese rats than
      from lean ones. Insulinotropic effect of acetylcholine was reported in islets of
      both animals, albeit less than in obese ones. Blockage of muscarinic M(2)
      receptor, using methoctramine at 1; 5 and 10 microM, increased acetylcholine
      secretory response in islets of obese rats, while no effect has been observed in
      lean ones. Results demonstrate that muscarinic M(2) receptors are functioning in
      pancreatic islets of MSG-obese rats. The inhibitory action of muscarinic M(2)
      receptor may be a mechanism by which acetylcholine discloses weak insulinotropic
      effect in MSG-obese rats.

PMID- 17174302
TI  - Zinc-desferrioxamine reduces damage to lenses exposed to hyperbaric oxygen and
      has an ameliorative effect on catalase and Na, K-ATPase activities.
AB  - Our purpose was to investigate the effects of exposure to high partial pressure
      of oxygen on lens optical quality and on the activities of lenticular catalase
      and Na, K-ATPase in culture and to examine the effect of zinc-desferrioxamine (Zn
      DFO) addition to cultured lenses exposed to high oxygen partial pressure on these
      parameters. Bovine lenses, kept in organ culture, were exposed to different
      combinations of partial pressure of oxygen with and without addition of Zn-DFO
      complex (20 microM) and examined during a 14-day period. Lens optical quality,
      catalase, and Na, K-ATPase activity were compared between study and control
      groups. Two hundred lenses were included in the present study. Decreased
      lenticular optical quality and decreased catalase and Na, K-ATPase activities
      were observed in lenses exposed to hyperbaric oxygen. Lenses exposed to
      normobaric oxygen showed a reduction in these parameters to a lesser degree. The
      damaging optical and enzymatic effects of oxygen on lenses in culture increased
      in magnitude along the culture period. Addition of Zn-DFO to the culture just
      before the exposure to hyperbaric oxygen eliminated most of the optical and
      enzymatic oxygen-induced damage. Addition of Zn-DFO after the first exposure
      demonstrated reduction in the oxidative damage induced reduction of optical
      quality in a time-dependent manner - the later the addition of Zn-DFO took place
      the smaller the protective effect observed. High oxygen load has toxic effects on
      bovine lenses in organ culture conditions as determined by optical parameters as
      well as reduction of catalase and Na, K-ATPase activities. These toxic effects
      can be attenuated by introducing Zn-DFO just before lenses are exposed to oxygen.
      The beneficial effect of Zn-DFO, applied after lenses have been exposed to
      hyperbaric oxygen, on the oxidative damage was time-dependent - the earlier the
      application the more significant the observed protective effect. The present
      results may indicate a possible future role for Zn-DFO as a protective agent
      against oxygen-induced human cataract formation.

PMID- 17174303
TI  - Melatonin in the eye: implications for glaucoma.
AB  - Melatonin synthesis occurs in the retina of most animals as well as in humans.
      Circadian oscillators that control retinal melatonin synthesis have been
      identified in the eyes of different animal species. The presence of melatonin
      receptors is demonstrable by immunocytochemical studies of ocular tissues. These
      receptors may have different functional roles in different parts of the eye. In
      view that melatonin is a potent antioxidant molecule, it can be effective in
      scavenging free radicals that are generated in ocular tissues. By this mechanism
      melatonin could protect the ocular tissues against disorders like glaucoma, age
      related macular degeneration, retinopathy of prematurity, photo-keratitis and
      cataracts. Although an increased intraocular pressure is an important risk factor
      in glaucoma, other concomitant phenomena like increased glutamate levels, altered
      nitric oxide metabolism and increased free radical generation seem to play a
      significant role in its pathogenesis. Data are discussed indicating that
      melatonin, being an efficient antioxidant with antinitridergic properties, has a
      promising role in the treatment and management of glaucoma.

PMID- 17174305
TI  - Erythropoietin delays disease onset in an amyotrophic lateral sclerosis model.
AB  - Erythropoietin (Epo) has been shown in the recent years to have neuroprotective
      activity in a variety of settings. In this study, we investigated its impact on
      the progression of paralysis in a mouse model simulating the human disorder
      amyotrophic lateral sclerosis (ALS). We found that Epo can delay the onset of
      motor deterioration in transgenic SOD G93A mice without prolonging their
      survival. Notably this effect was selective for the females only. These initial
      findings encourage further investigation of this biological avenue in the search
      for improved remedies for this fatal disease.

PMID- 17174304
TI  - Neurobehavioral functional deficits following closed head injury in the neonatal
      pig.
AB  - Neurobehavioral deficits in higher cortical systems have not been described
      previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day
      old piglets were subjected to either mild (142 rad/s) or moderate (188 rad/s)
      rapid non-impact axial rotations of the head. Multiple domains of cortical
      function were evaluated 5 times during the 12 day post-injury period using tests
      of neurobehavioral function devised for piglets. There were no observed
      differences in neurobehavioral outcomes between mild injury pigs (N=8) and
      instrumented shams (N=4). Moderately injured piglets (N=7) had significantly
      lower interest in exploring their environment and had higher failure rates in
      visual-based problem solving compared to instrumented shams (N=5) on days 1 and 4
      after injury. Neurobehavioral functional deficits correlated with neuropathologic
      damage in the neonatal pigs after inertial head injury. Injured axons detected by
      immunohistochemistry (beta-APP) were absent in mild injury and sham piglets, but
      were observed in moderately injured piglet brains. In summary, we have developed
      a quantitative battery of neurobehavioral functional assessments for large
      animals that correlate with neuropathologic axonal damage and may have wide
      applications in the fields of cardiac resuscitation, stroke, and hypoxic-ischemic
      brain injury.

PMID- 17174306
TI  - hnRNP-U enhances the expression of specific genes by stabilizing mRNA.
AB  - Heterogeneous nuclear ribonucleoproteins (hnRNPs) are thought to be involved in
      pre-mRNA processing. hnRNP-U, also termed scaffold attachment factor A (SAF-A),
      binds to pre-mRNA and nuclear matrix/scaffold attachment region DNA elements.
      However, its role in the regulation of gene expression is as yet poorly
      understood. In the present study, we show that hnRNP-U specifically enhances the
      expression of tumor necrosis factor alpha mRNA by increasing its stability,
      possibly through binding to the 3' untranslated region. We also show that hnRNP-U
      enhances the expression of several other genes as well, including GADD45A,
      HEXIM1, HOXA2, IER3, NHLH2, and ZFY, by binding to and stabilizing these mRNAs.
      These results suggest that hnRNP-U enhances the expression of specific genes by
      regulating mRNA stability.

PMID- 17174307
TI  - MARCH-IX mediates ubiquitination and downregulation of ICAM-1.
AB  - The membrane associated RING-CH (MARCH) family of genes encode a novel group of
      RING-type ubiquitin E3 ligases. Overexpression of one of these family members,
      MARCH-IX, leads to a downregulation of cell surface major histocompatibility
      complex (MHC) class I and CD4. Here, we identify MARCH-IX as the first ubiquitin
      E3 ligase to control expression of the critical cell adhesion molecule ICAM-1.
      MARCH-IX expression causes ubiquitination and downregulation of ICAM-1 and a
      short alternative transcript of MARCH-IX lacking the RING-CH domain, termed MARCH
      IX RINGless, is shown to act as a positive regulator of MARCH-IX activity.

PMID- 17174308
TI  - D-pinitol regulates Th1/Th2 balance via suppressing Th2 immune response in
      ovalbumin-induced asthma.
AB  - D-pinitol has been demonstrated to exert insulin-like and anti-inflammatory
      activities. However, its anti-allergic effect in the Th1/Th2 immune response is
      poorly understood. Recently, it was shown that T-bet and GATA-3 are master Th1
      and Th2 regulatory transcription factors. In this study, we have attempted to
      determine whether D-pinitol regulates Th1/Th2 cytokine production, T-bet and GATA
      3 gene expression in OVA-induced asthma model mice. We also examined to ascertain
      whether D-pinitol could influence eosinophil peroxidase (EPO) activity. After
      being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic
      reactions. These reactions included an increase in the number of eosinophils in
      bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration
      into the lung tissue around blood vessels and airways, airway luminal narrowing,
      and the development of airway hyper-responsiveness (AHR). The administration of D
      pinitol before the last airway OVA challenge resulted in a significant inhibition
      of all asthmatic reactions. Accordingly, this study may provide evidence that D
      pinitol plays a critical role in the amelioration of the pathogenetic process of
      asthma in mice. These findings provide new insight into the immunopharmacological
      role of D-pinitol in terms of its effects in a murine model of asthma, and also
      broaden current perspectives in our understanding of the immunopharmacological
      functions of D-pinitol.

PMID- 17174309
TI  - Identification of the WW domain-interaction sites in the unstructured N-terminal
      domain of EBV LMP 2A.
AB  - Epstein-Barr virus latency is maintained by the latent membrane protein (LMP) 2A,
      which mimics the B-cell receptor (BCR) and perturbs BCR signaling. The
      cytoplasmic N-terminal domain of LMP2A is composed of 119 amino acids. The N
      terminal domain of LMP2A (LMP2A NTD) contains two PY motifs (PPPPY) that interact
      with the WW domains of Nedd4 family ubiquitin-protein ligases. Based on our
      analysis of NMR data, we found that the LMP2A NTD adopts an overall random-coil
      structure in its native state. However, the region between residues 60 and 90 was
      relatively ordered, and seemed to form the hydrophobic core of the LMP2A NTD.
      This region resides between two PY motifs and is important for WW domain binding.
      Mapping of the residues involved in the interaction between the LMP2A NTD and WW
      domains was achieved by chemical shift perturbation, by the addition of WW2 and
      WW3 peptides. Interestingly, the binding of the WW domains mainly occurred in the
      hydrophobic core of the LMP2A NTD. In addition, we detected a difference in the
      binding modes of the two PY motifs against the two WW peptides. The binding of
      the WW3 peptide caused the resonances of five residues (Tyr(60), Glu(61),
      Asp(62), Trp(65), and Gly(66)) just behind the N-terminal PY motif of the LMP2A
      NTD to disappear. A similar result was obtained with WW2 binding. However, near
      the C-terminal PY motif, the chemical shift perturbation caused by WW2 binding
      was different from that due to WW3 binding, indicating that the residues near the
      PY motifs are involved in selective binding of WW domains. The present work
      represents the first structural study of the LMP2A NTD and provides fundamental
      structural information about its interaction with ubiquitin-protein ligase.

PMID- 17174310
TI  - Single and cell population respiratory oscillations in yeast: a 2-photon scanning
      laser microscopy study.
AB  - Two-photon scanning laser and confocal microscopies were used to image metabolic
      dynamics of single or cell populations of Saccharomyces cerevisiae strain 28033.
      Autofluorescence of reduced nicotinamide nucleotides, and mitochondrial membrane
      potential (DeltaPsim), were simultaneously monitored. Spontaneous, large-scale
      synchronized oscillations of NAD(P)H and DeltaPsim throughout the entire
      population of yeasts occurred under perfusion with aerated buffer in a continuous
      single-layered film of organisms. These oscillations stopped in the absence of
      perfusion and the intracellular NAD(P)H pool became reduced. Individual
      mitochondria within a single yeast also showed in-phase synchronous responses
      with the cell population, in both tetramethylrhodamine ethyl ester (or
      tetramethylrhodamine methyl ester) and autofluorescence. A single, localized,
      laser flash also triggered mitochondrial oscillations in single cells suggesting
      that the mitochondrion may behave as an autonomous oscillator. We conclude that
      spontaneous oscillations of S. cerevisiae mitochondrial redox states and
      DeltaPsim occur within individual yeasts, and synchrony of populations of
      organisms indicates the operation of an efficient system of cell-cell interaction
      to produce concerted metabolic multicellular behaviour on the minute time scale
      in both cases.

PMID- 17174311
TI  - Determination of the Plk4/Sak consensus phosphorylation motif using peptide spots
      arrays.
AB  - The family of polo like kinases (Plks) regulate cell cycle progression through
      key functional roles in mitosis. While the four mammalian family members, Plk1-4,
      share overlapping functions, each member possesses unique functions that may be
      dictated in part by their ability to phosphorylate different substrates. Numerous
      cellular substrates for Plk1, 2, and 3 have been characterized, but the protein
      targets for Plk4/Sak remain unknown. We have purified the kinase domain of Sak
      and demonstrated that it has robust kinase activity in vitro. Using in vitro
      kinase assays on peptide spots arrays, we determined the consensus
      phosphorylation motif for Sak to be yen-[Ile/Leu/Val]-Ser/Thr-phi-phi-X- yen/Pro
      (where phi denotes a large hydrophobic residue, yen is a charged residue
      dependent on the context of the surrounding sequence, and residues in brackets
      are unfavoured). This consensus phosphorylation motif differs from that of Plk1,
      and provides a basis for future studies to identify in vivo substrates of Sak.

PMID- 17174312
TI  - Epac- and Rap- independent ERK1/2 phosphorylation induced by Gs-coupled receptor
      stimulation in HEK293 cells.
AB  - Serotonin activates Ras and Ras-dependent ERK1/2 phosphorylation in HEK293 cells
      expressing G(s)-coupled 5-HT(4) or 5-HT(7) serotonin receptors through unknown
      mechanisms. Both Epac/Rap-dependent and -independent pathways for Ras-dependent
      ERK1/2 activation have been suggested. Epac overexpression or Epac-specific 8-CPT
      2'-O-Me-cAMP did not cause ERK1/2 phosphorylation, despite Rap activation. The
      data did not support a role for PLCepsilon or DAG-dependent Ras GEFs of the Ras
      GRP family in Ras-dependent ERK1/2 phosphorylation. However, serotonin stimulated
      phosphorylation of endogenous and recombinant Ras-GRF1, increased [Ca(2+)](i) and
      caused Ca(2+)- and calmodulin-dependent ERK1/2 phosphorylation. Different
      signalling pathways seem to be utilised by G(s)-coupled receptors in various
      isolates of HEK293 cells.

PMID- 17174313
TI  - Overrepresentation of interactions between homologous proteins in interactomes.
AB  - It is well proved that the probability that a protein interacts with itself is
      higher than that it interacts with another protein. It has been recently shown
      that the probability of interaction is also higher for proteins with significant
      sequence similarity. In this paper we show that proteins sharing identical PFAM
      domains interact more often than expected by chance in Saccharomyces cerevisiae
      and Escherichia coli. We also analyze the variety of domain interfaces used by
      homologous proteins to interact and show that the overrepresentation of
      interactions between homological proteins is not caused by small number of pairs
      of identical "sticky domains" shared between interacting proteins.

PMID- 17174315
TI  - Evaluation of a gas chromatography/mass spectrometry method for the
      quantification of carboxymethyllysine in food samples.
AB  - An accurate method for the quantification of carboxymethyllysine (CML) in food
      samples is evaluated. CML, a stable advanced Maillard compound, is considered as
      an useful marker of protein damage in severely heated foods. The proposed GC-MS
      method stipulates double derivatisation of amino acids and quantification by
      selected ion monitoring. Relative error of repeatability was further improved
      from 5 to 1% by replacing internal standard by isotope dilution. Comparison with
      enzyme linked immunosorbent assay (ELISA) was performed on infant formulas, with
      satisfactory results in powdered but not in liquid formulas. Quantification of
      CML in several food matrices allowed evidencing CML formation in food products
      containing reducing sugar only.

PMID- 17174316
TI  - Enantiomeric monoterpene emissions from natural and damaged Scots pine in a
      boreal coniferous forest measured using solid-phase microextraction and gas
      chromatography/mass spectrometry.
AB  - In order to develop a valuable method for accurate screening of biogenic
      emissions from undisturbed living plants or for plant-insect interactions, solid
      phase microextraction (SPME) has been combined with dynamic branch enclosure
      cuvettes and enantioselective GC/MS. The study was conducted at Hyytiala forest
      station, Finland within a boreal coniferous forest dominated by Scots pine (Pinus
      sylvestris). The SPME method was optimized for monoterpenes by testing three
      fibre coatings: polydimethylsiloxane (PDMS), polydimethylsiloxane/divinylbenzene
      (PDMS/DVB) and carbowax/divinylbenzene (CW/DVB) and determining the optimum
      exposure time. The PDMS/DVB fibre was found to be most suitable and was used to
      characterize emissions of P. sylvestris enclosed in dynamic branch enclosure
      cuvettes by exposure for 1 min followed by desorption and separation on a beta
      cyclodextrin column installed in the GC/MS oven. Dynamic cuvette measurements
      have been compared to static headspace SPME samples of the emission of detached
      needles from the same tree species and a portable dynamic air sampler (PDAS)-SPME
      for sampling the ambient air around the same trees. The method developed has
      allowed an accurate characterization of the gaseous emission of P. sylvestris and
      the identification of 17 isoprenoids comprising chiral and achiral monoterpenes.
      Two chemotypes of Scots pine can be differentiated through their emission of (+)
      delta-3-carene. While SPME-dynamic cuvette, portable dynamic sampler and
      absorbent results agreed well, significant differences in enantiomeric ratios
      were observed in natural emissions and those of damaged leaves. Therefore, in
      enantioselective studies of plant-insect and/or plant-plant interactions, the two
      enantiomers of a given monoterpene should be treated as two separate substances.

PMID- 17174318
TI  - Isolation and purification of flavonoid and isoflavonoid compounds from the
      pericarp of Sophora japonica L. by adsorption chromatography on 12% cross-linked
      agarose gel media.
AB  - A method for isolation and purification of flavonoid and isoflavonoid compounds
      in extracts of the pericarp of Sophora japonica L. was established by adsorption
      chromatography on the 12% cross-linked agarose gel Superose 12. The crude
      extracts were pre-separated to two parts, sample A and sample B, on a D-101
      macroporous resin column by elution with 20% ethanol and 40% ethanol,
      respectively. Samples A and B were then separated by adsorption chromatography on
      Superose 12 with 40% methanol as the mobile phase. Eight compounds including four
      kinds of flavonoids and four kinds of isoflavonoids were obtained by the proposed
      method. The adsorption mechanisms of flavonoids and isoflavonoids on Superose 12
      were also discussed.

PMID- 17174314
TI  - Sirolimus blocks the accumulation of hyaluronan (HA) by arterial smooth muscle
      cells and reduces monocyte adhesion to the ECM.
AB  - Sirolimus (SRL), an inhibitor of human arterial smooth muscle cell (ASMC)
      proliferation and migration, prevents in-stent restenosis (ISR). Little is known
      about the effect of SRL on the extracellular matrix (ECM) component, hyaluronan,
      a key macromolecule in neointimal hyperplasia and inflammation. In this study, we
      investigated SRL regulation of the synthesis of hyaluronan by cultured human ASMC
      and the effect of SRL on hyaluronan mediated monocyte adhesion to the ECM.
      Hyaluronan production on a per cell basis was significantly inhibited by SRL at 4
      days and remained so through 10 days. This reduction was correlated with reduced
      levels of hyaluronan synthase mRNAs while hyaluronan degradation rates were
      unchanged. Poly I:C, a viral mimetic, caused increased hyaluronan accumulation by
      ASMC cell layers and this increase was inhibited by SRL. The inhibition was
      paralleled by a reduction in hyaluronan-dependent monocyte adhesion to the ECM.
      This study demonstrates that SRL not only regulates the proliferation of ASMC but
      reduces the production of hyaluronan by these cells. This alteration in ECM
      composition results in reduced monocyte adhesion to the ECM in cultures of ASMC.
      Alterations in hyaluronan accumulation may contribute to the inhibition of ISR
      that is achieved by SRL.

PMID- 17174319
TI  - In situ derivatization hollow fiber mediated liquid phase microextraction of
      alkylphosphonic acids from water.
AB  - Alkylphosphonic acids (APAs), particularly the methyl-, ethyl-, isopropyl- and n
      propyl-phosphonic acids are important markers of extremely toxic nerve agents.
      Hence, their detection and identification is of vital importance to verification
      of chemical weapons convention (CWC). Verification analysis of CWC requires
      development of fast, reliable, simple and reproducible sample preparation methods
      of water and soil samples. Present investigation is focused on the optimization
      of alkylation of APAs in water with subsequent extraction of alkylated acids by
      hollow fiber liquid phase microextraction (HF-LPME). This simple and sensitive
      sample preparation of APAs from water offered better recoveries in comparison to
      conventionally used extraction technique. Under optimized conditions, the APAs
      were detected at the concentration of 0.5-0.75 microg/mL with S/N ratio > or = 5,
      whereas the LODs for alkyl APAs (monobasic APAs) were achieved up to 0.1
      microg/mL. The developed method was finally tested with water samples supplied in
      19th official proficiency test conducted by the OPCW.

PMID- 17174320
TI  - Use of monolithic supports in proteomics technology.
AB  - An overview on the utilization of monoliths in proteomics technology will be
      given. Both silica- and polymer-based monoliths have broad use for
      microseparation of tryptic peptides in reversed-phase (RP) mode before
      identification by mass spectrometry (MS) or by MS/MS. For two-dimensional (2D) LC
      separation of peptides before MS or MS/MS analysis, a combination of ion
      exchange, usually cation-exchange (CEX) chromatography with RP chromatography on
      monolithic supports can be employed. Immobilized metal ion affinity
      chromatography monoliths with immobilized Fe3+-ions are used for the isolation of
      phosphopeptides. Monoliths with immobilized affinity ligands are usually applied
      to the rapid separation of proteins and peptides. Miniaturized reactors with
      immobilized proteolytic enzymes are utilized for rapid on- or offline digestion
      of isolated proteins or protein mixtures prior to identification by LC-MS/MS.
      Monoliths also have broad potential for application in sample preparation, prior
      to further proteomic analyses. Monolithic supports with large pore sizes can be
      exploited for the isolation of nanoparticles, such as cells, organelles, viruses
      and protein aggregates. The potential for further adoption of monolithic supports
      in protein separation and enrichment of low abundance proteins prior to
      proteolytic digestion and final LC-MS/MS protein identification will be
      discussed.

PMID- 17174321
TI  - Surface properties of kaolin and illite suspensions in concentrated calcium
      hydroxide medium.
AB  - The adsorption behaviour of calcium hydroxide onto illite and kaolin clay
      minerals was investigated by monitoring with atomic emission spectroscopy and pH
      measurements the amounts of ions left in solution after exposing clay minerals to
      calcium hydroxide solutions of various concentrations. Both clay minerals can
      adsorb calcium and hydroxyl ions. Rather than just considering proton exchanges
      at the clay mineral surfaces, the adsorption is explained by an approach based on
      Lewis description of molecules. With this approach, a mechanism for calcium
      hydroxide adsorption not only at the edges of the clay particles but also onto
      the faces is proposed. In order to gain a better insight onto the active groups
      at the surface of the studied clay minerals, adsorption of pyridine and ammonia
      on illite and kaolin was followed by FTIR spectroscopy. These measurements gave
      the signature of edges, which are marginally involved in interactions with
      calcium ions.

PMID- 17174322
TI  - Long-term stable expression of human growth hormone by rAAV promotes myocardial
      protection post-myocardial infarction.
AB  - Recombinant adeno-associated virus (rAAV)-based gene therapy represents a
      promising approach for the treatment of heart diseases. It has been shown that
      growth hormone (GH) exerts a favorable effect on cardiovascular function in
      clinical and animal studies. This study explores a chronic stage after myocardial
      infarction and the potential therapeutic effects of delivering a human GH gene by
      rAAV following coronary artery ligation in Sprague-Dawley rats. rAAV vectors
      stably transduced heart muscle for up to 22 weeks after myocardial infarction
      (MI). Overexpression of GH via rAAV vectors significantly improved not only
      cardiac function but also LV pathologic remodeling was attenuated post-MI
      compared to the control rAAV-lacZ injected group. rAAV-mediated expression of GH
      also resulted in a significant induction of several angiogenic genes such as
      eNOS, VEGF and bFGF in rat hearts. Immunohistochemistry revealed an increase in
      capillary density and proliferation of cells and a decrease in the number of
      TUNEL-positive cardiomyocytes in the rAAV-GH group. Based on these data, we
      conclude that rAAV-mediated GH delivery can render a long-term transduction in
      the infarcted heart and improve cardiac function through promoting angiogenesis
      and proliferation of cells and protecting cardiomyocytes from ischemia-induced
      apoptosis.

PMID- 17174323
TI  - Upregulation of TRPC1 in the development of cardiac hypertrophy.
AB  - The importance of Ca(2+) entry in the cardiac hypertrophic response is well
      documented, but the actual Ca(2+) entry channels remain unknown. Transient
      receptor potential (TRP) proteins are thought to form either homo- or heteromeric
      Ca(2+) entry channels that are involved in the proliferation and differentiation
      of various cells. The purpose of this study was to explore the potential
      involvement of TRP channels in the development of cardiac hypertrophy. The mRNA
      and protein expression of several TRP channel subunits were evaluated using
      hearts from abdominal aortic-banded (AAB) rats. Although TRPs C1, C3, C5, and C6
      were constitutively expressed, only TRPC1 expression was significantly increased
      in the hearts of AAB rats compared to sham-operated rats. Using primary cultures
      of neonatal rat cardiomyocytes, we detected increases in the expression of TRPC1,
      brain natriuretic peptide (BNP), and atrial natriuretic factor (ANF), as well as
      increases in store-operated Ca(2+) entry (SOCE) and cell surface area, following
      endothelin-1 (ET-1) treatment. Silencing of the TRPC1 gene via small interfering
      RNA (siRNA) attenuated SOCE and prevented ET-1-, angiotensin-II (AT II)-, and
      phenylephrine (PE)-induced cardiac hypertrophy. In HEK 293T cells, overexpression
      of TRPC1 augmented SOCE, leading to an increase in nuclear factor of activated T
      cells (NFAT) promoter activity, while co-transfection with dominant-negative
      forms of TRPC1 suppressed it. In conclusion, TRPC1 functions in Ca(2+) influx,
      and its upregulation is involved in the development of cardiac hypertrophy;
      moreover, it plays an important role in the regulation of the signaling pathways
      that govern cardiac hypertrophy. These findings establish TRPC1 as a functionally
      important regulator of cardiac hypertrophy.

PMID- 17174324
TI  - E(z), a depth-dependent potential for assessing the energies of insertion of
      amino acid side-chains into membranes: derivation and applications to determining
      the orientation of transmembrane and interfacial helices.
AB  - We have developed an empirical residue-based potential (E(z) potential) for
      protein insertion in lipid membranes. Propensities for occurrence as a function
      of depth in the bilayer were calculated for the individual amino acid types from
      their distribution in known structures of helical membrane proteins. The
      propensities were then fit to continuous curves and converted to a potential
      using a reverse-Boltzman relationship. The E(z) potential demonstrated a good
      correlation with experimental data such as amino acid transfer free energy scales
      (water to membrane center and water to interface), and it incorporates
      transmembrane helices of varying composition in the membrane with trends similar
      to those obtained with translocon-mediated insertion experiments. The potential
      has a variety of applications in the analysis of natural membrane proteins as
      well as in the design of new ones. It can help in calculating the propensity of
      single helices to insert in the bilayer and estimate their tilt angle with
      respect to the bilayer normal. It can be utilized to discriminate amphiphilic
      helices that assume a parallel orientation at the membrane interface, such as
      those of membrane-active peptides. In membrane protein design applications, the
      potential allows an environment-dependent selection of amino acid identities.

PMID- 17174325
TI  - Coliphage N4 N-acetylmuramidase defines a new family of murein hydrolases.
AB  - Escherichia coli phage N4 infection leads to delayed host cell lysis, 3000
      particles per infected bacterium and a small plaque phenotype. We show that
      bacteriophage N4 encodes a murein hydrolase (gp61) that is essential for N4
      plaque-forming ability. gp61 has a high level of sequence similarity to
      hypothetical proteobacterial proteins, and Vibrio harveyi phage VHML ORF 19. Nano
      electrospray ionization (nESI) quadrupole ion trap (QIT) mass spectrometry (MS)
      analysis of muropeptides from purified gp61 digestion of E. coli peptidoglycan
      indicates that gp61 is an N-acetylmuramidase. The EGGY motif present near the N
      terminus of gp61 and its homologs contains the glutamic acid residue essential
      for enzymatic activity. These results provide evidence that N4 gp61 and its
      homologs define a new family of N-acetylmuramidases (pfam05838.4, DUF847,
      COG3926). In contrast to its homologs, gp61 contains an N-terminal signal
      sequence. When expressed at levels present during phage infection, gp61 localizes
      primarily to the cell inner membrane; in contrast, over-expression of recombinant
      N4 gp61 is sufficient for rapid cell lysis. Overproduction of the recombinant
      Salmonella typhimurium (STM0016) homolog is sufficient for cell lysis only when
      fused to the gp61 N-terminal signal sequence. The results of subcellular
      localization and of mutagenesis of the gp61 N-terminal signal sequence indicate
      that gp61 must be released from the inner membrane to be catalytically active.

PMID- 17174326
TI  - Magnesium-cationic dummy atom molecules enhance representation of DNA polymerase
      beta in molecular dynamics simulations: improved accuracy in studies of
      structural features and mutational effects.
AB  - Human DNA polymerase beta (pol beta) fills gaps in DNA as part of base excision
      DNA repair. Due to its small size it is a convenient model enzyme for other DNA
      polymerases. Its active site contains two Mg(2+) ions, of which one binds an
      incoming dNTP and one catalyzes its condensation with the DNA primer strand.
      Simulating such binuclear metalloenzymes accurately but computationally
      efficiently is a challenging task. Here, we present a magnesium-cationic dummy
      atom approach that can easily be implemented in molecular mechanical force fields
      such as the ENZYMIX or the AMBER force fields. All properties investigated here,
      namely, structure and energetics of both Michaelis complexes and transition state
      (TS) complexes were represented more accurately using the magnesium-cationic
      dummy atom model than using the traditional one-atom representation for Mg(2+)
      ions. The improved agreement between calculated free energies of binding of TS
      models to different pol beta variants and the experimentally determined
      activation free energies indicates that this model will be useful in studying
      mutational effects on catalytic efficiency and fidelity of DNA polymerases. The
      model should also have broad applicability to the modeling of other magnesium
      containing proteins.

PMID- 17174329
TI  - The solution structure of antigen MPT64 from Mycobacterium tuberculosis defines a
      new family of beta-grasp proteins.
AB  - The MPT64 protein and its homologs form a highly conserved family of secreted
      proteins with unknown function that are found within the pathogenic Mycobacteria
      genus. The founding member of this family from Mycobacterium tuberculosis (MPT64
      or protein Rv1980c) is expressed only when Mycobacteria cells are actively
      dividing. By virtue of this relatively unique expression profile, Rv1980c is
      currently under phase III clinical trials to evaluate its potential to replace
      tuberculin, or purified protein derivative, as the rapid diagnostic of choice for
      detection of active tuberculosis infection. We describe here the NMR solution
      structure of Rv1980c. This structure reveals a previously undescribed fold that
      is based upon a variation of a beta-grasp motif most commonly found in protein
      protein interaction domains. Examination of this structure in conjunction with
      multiple sequence alignments of MPT64 homologs identifies a candidate ligand
      binding site, which may help guide future studies of Rv1980c function. The work
      presented here also suggests structure-based approaches for increasing the
      antigenic potency of a Rv1980c-based diagnostic.

PMID- 17174330
TI  - Serpin acceleration of amyloid fibril formation: a role for accessory proteins.
AB  - Protein aggregation underlies an increasing number of human diseases. Recent
      experiments have shown that the aggregation reaction is exquisitely specific
      involving particular interactions between non-native proteins. However,
      aggregation of certain proteins, for example beta-amyloid, in vivo leads to the
      recruitment of other proteins into the aggregate. Antichymotrypsin, a non-fibril
      forming protein, is always observed to be associated with beta-amyloid plaques in
      Alzheimer's sufferers. The role of antichymotrypsin is controversial with studies
      showing it can either accelerate or inhibit the aggregation reaction. To
      investigate the role of antichymotrypsin in fibrillogenesis we have studied its
      interaction with apolipoprotein C-II, a well characterized model system for the
      study of fibrillogenesis. Our data demonstrate that sub-stoichiometric amounts of
      antichymotrypsin and its alternate structural forms can dramatically accelerate
      the aggregation of apolipoprotein C-II, whereas the presence of alpha(1)
      antitrypsin, a structural homologue of antichymotrypsin, cannot. Sedimentation
      velocity experiments show more apolipoprotein C-II fibrils were formed in the
      presence of antichymotrypsin. Using pull-down assays and immuno-gold labeling we
      demonstrate an interaction between antichymotrypsin and apolipoprotein C-II
      fibrils that specifically occurs during fibrillogenesis. Taken together these
      data demonstrate an interaction between antichymotrypsin and apolipoprotein C-II
      that accelerates fibrillogenesis and indicates a specific role for accessory
      proteins in protein aggregation.

PMID- 17174328
TI  - Amino acid contribution to protein solubility: Asp, Glu, and Ser contribute more
      favorably than the other hydrophilic amino acids in RNase Sa.
AB  - Poor protein solubility is a common problem in high-resolution structural
      studies, formulation of protein pharmaceuticals, and biochemical characterization
      of proteins. One popular strategy to improve protein solubility is to use site
      directed mutagenesis to make hydrophobic to hydrophilic mutations on the protein
      surface. However, a systematic investigation of the relative contributions of all
      20 amino acids to protein solubility has not been done. Here, 20 variants at the
      completely solvent-exposed position 76 of ribonuclease (RNase) Sa are made to
      compare the contributions of each amino acid. Stability measurements were also
      made for these variants, which occur at the i+1 position of a type II beta-turn.
      Solubility measurements in ammonium sulfate solutions were made at high positive
      net charge, low net charge, and high negative net charge. Surprisingly, there was
      a wide range of contributions to protein solubility even among the hydrophilic
      amino acids. The results suggest that aspartic acid, glutamic acid, and serine
      contribute significantly more favorably than the other hydrophilic amino acids
      especially at high net charge. Therefore, to increase protein solubility,
      asparagine, glutamine, or threonine should be replaced with aspartic acid,
      glutamic acid or serine.

PMID- 17174327
TI  - X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl acyl carrier
      protein synthase II (mtKasB).
AB  - Mycolic acids are long chain alpha-alkyl branched, beta-hydroxy fatty acids that
      represent a characteristic component of the Mycobacterium tuberculosis cell wall.
      Through their covalent attachment to peptidoglycan via an arabinogalactan
      polysaccharide, they provide the basis for an essential outer envelope membrane.
      Mycobacteria possess two fatty acid synthases (FAS); FAS-I carries out de novo
      synthesis of fatty acids while FAS-II is considered to elongate medium chain
      length fatty acyl primers to provide long chain (C(56)) precursors of mycolic
      acids. Here we report the crystal structure of Mycobacterium tuberculosis beta
      ketoacyl acyl carrier protein synthase (ACP) II mtKasB, a mycobacterial
      elongation condensing enzyme involved in FAS-II. This enzyme, along with the M.
      tuberculosis beta-ketoacyl ACP synthase I mtKasA, catalyzes the Claisen-type
      condensation reaction responsible for fatty acyl elongation in FAS-II and are
      potential targets for development of novel anti-tubercular drugs. The crystal
      structure refined to 2.4 A resolution revealed that, like other KAS-II enzymes,
      mtKasB adopts a thiolase fold but contains unique structural features in the
      capping region that may be crucial to its preference for longer fatty acyl chains
      than its counterparts from other bacteria. Modeling of mtKasA using the mtKasB
      structure as a template predicts the overall structures to be almost identical,
      but a larger entrance to the active site tunnel is envisaged that might
      contribute to the greater sensitivity of mtKasA to the inhibitor thiolactomycin
      (TLM). Modeling of TLM binding in mtKasB shows that the drug fits the active site
      poorly and results of enzyme inhibition assays using TLM analogues are wholly
      consistent with our structural observations. Consequently, the structure
      described here further highlights the potential of TLM as an anti-tubercular lead
      compound and will aid further exploration of the TLM scaffold towards the design
      of novel compounds, which inhibit mycobacterial KAS enzymes more effectively.

PMID- 17174331
TI  - Direct observation of microscopic reversibility in single-molecule protein
      folding.
AB  - Both folded and unfolded conformations should be observed for a protein at its
      melting temperature (T(m)), where DeltaG between these states is zero. In an all
      atom molecular dynamics simulation of chymotrypsin inhibitor 2 (CI2) at its
      experimental T(m), the protein rapidly loses its low-temperature native
      structure; it then unfolds before refolding to a stable, native-like
      conformation. The initial unfolding follows the unfolding pathway described
      previously for higher-temperature simulations: the hydrophobic core is disrupted,
      the beta-sheet pulls apart and the alpha-helix unravels. The unfolded state
      reached under these conditions maintains a kernel of structure in the form of a
      non-native hydrophobic cluster. Refolding simply reverses this path, the side
      chain interactions shift, the helix refolds, and the native packing and hydrogen
      bonds are recovered. The end result of this refolding is not the initial crystal
      structure; it contains the proper topology and the majority of the native
      contacts, but the structure is expanded and the contacts are long. We believe
      this to be the native state at elevated temperature, and the change in volume and
      contact lengths is consistent with experimental studies of other native proteins
      at elevated temperature and the chemical denaturant equivalent of T(m).

PMID- 17174333
TI  - Lipid chain selectivity by outer membrane phospholipase A.
AB  - Outer membrane phospholipase A (OMPLA) is a unique, integral membrane enzyme
      found in Gram-negative bacteria and is an important virulence factor for
      pathogens such as Helicobacter pylori. This broad-specificity lipase degrades a
      variety of lipid substrates, and it plays a direct role in adjusting the
      composition and permeability of bacterial membranes under conditions of stress.
      Interestingly, OMPLA shows little preference for the lipid headgroup and,
      instead, the length of the hydrophobic acyl chain is the strongest determinant
      for substrate selection by OMPLA, with the enzyme strongly preferring substrates
      with chains equal to or longer than 14 carbon atoms. The question remains as to
      how a hydrophobic protein like OMPLA can achieve this specificity, particularly
      when the shorter chains can be accommodated in the binding pocket. Using a series
      of sulfonyl fluoride inhibitors with various lengths of acyl chain, we show here
      that the thermodynamics of substrate-induced OMPLA dimerization are guided by the
      acyl chain length, demonstrating that OMPLA uses a unique biophysical mechanism
      to select its phospholipid substrate.

PMID- 17174332
TI  - Structure and function of a mycobacterial NHEJ DNA repair polymerase.
AB  - Non homologous end-joining (NHEJ)-mediated repair of DNA double-strand breaks in
      prokaryotes requires Ku and a specific multidomain DNA ligase (LigD). We present
      crystal structures of the primase/polymerisation domain (PolDom) of Mycobacterium
      tuberculosis LigD, alone and complexed with nucleotides. The PolDom structure
      combines the general fold of the archaeo-eukaryotic primase (AEP) superfamily
      with additional loops and domains that together form a deep cleft on the surface,
      likely used for DNA binding. Enzymatic analysis indicates that the PolDom of
      LigD, even in the absence of accessory domains and Ku proteins, has the potential
      to recognise DNA end-joining intermediates. Strikingly, one of the main signals
      for the specific and efficient binding of PolDom to DNA is the presence of a 5'
      phosphate group, located at the single/double-stranded junction at both gapped
      and 3'-protruding DNA molecules. Although structurally unrelated, Pol lambda and
      Pol mu, the two eukaryotic DNA polymerases involved in NHEJ, are endowed with a
      similar capacity to bind a 5'-phosphate group. Other properties that are
      beneficial for NHEJ, such as the ability to generate template distortions and
      realignments of the primer, displayed by Pol lambda and Pol mu, are shared by the
      PolDom of bacterial LigD. In addition, PolDom can perform non-mutagenic
      translesion synthesis on termini containing modified bases. Significantly,
      ribonucleotide insertion appears to be a recurrent theme associated with NHEJ,
      maximised in this case by the deployment of a dedicated primase, although its in
      vivo relevance is unknown.

PMID- 17174334
TI  - Two structures of alliinase from Alliium sativum L.: apo form and ternary complex
      with aminoacrylate reaction intermediate covalently bound to the PLP cofactor.
AB  - Alliinase (alliin lyase EC 4.4.1.4), a PLP-dependent alpha, beta-eliminating
      lyase, constitutes one of the major protein components of garlic (Alliium sativum
      L.) bulbs. The enzyme is a homodimeric glycoprotein and catalyzes the conversion
      of a specific non-protein sulfur-containing amino acid alliin ((+S)-allyl-L
      cysteine sulfoxide) to allicin (diallyl thiosulfinate, the well known
      biologically active component of freshly crushed garlic), pyruvate and ammonia.
      The enzyme was crystallized in the presence of (+S)-allyl-L-cysteine, forming
      dendrite-like monoclinic crystals. In addition, intentionally produced apo-enzyme
      was crystallized in tetragonal form. These structures of alliinase with
      associated glycans were resolved to 1.4 A and 1.61 A by molecular replacement.
      Branched hexasaccharide chains N-linked to Asn146 and trisaccharide chains N
      linked to Asn328 are seen. The structure of hexasaccharide was found similar to
      "short chain complex vacuole type" oligosaccharide most commonly seen in plant
      glycoproteins. An unexpected state of the enzyme active site has been observed in
      the present structure. The electron density in the region of the cofactor made it
      possible to identify the cofactor moiety as aminoacrylate intermediate covalently
      bound to the PLP cofactor. It was found in the present structure to be stabilized
      by large number of interactions with surrounding protein residues. Moreover, the
      existence of the expected internal aldimine bond between the epsilon-amino group
      of Lys251 and the aldehyde of the PLP is ruled out on the basis of a distinct
      separation of electron density of Lys251. The structure of the active site cavity
      in the apo-form is nearly identical to that seen in the holo-form, with two
      sulfate ions, an acetate and several water molecules from crystallization
      conditions that replace and mimic the PLP cofactor.

PMID- 17174335
TI  - Stabilizing IkappaBalpha by "consensus" design.
AB  - IkappaBalpha is the major regulator of transcription factor NF-kappaB function.
      The ankyrin repeat region of IkappaBalpha mediates specific interactions with NF
      kappaB dimers, but ankyrin repeats 1, 5 and 6 display a highly dynamic character
      when not in complex with NF-kappaB. Using chemical denaturation, we show here
      that IkappaBalpha displays two folding transitions: a non-cooperative conversion
      under weak perturbation, and a major cooperative folding phase upon stronger
      insult. Taking advantage of a native Trp residue in ankyrin repeat (AR) 6 and
      engineered Trp residues in AR2, AR4 and AR5, we show that the cooperative
      transition involves AR2 and AR3, while the non-cooperative transition involves
      AR5 and AR6. The major structural transition can be affected by single amino acid
      substitutions converging to the "consensus" ankyrin repeat sequence, increasing
      the native state stability significantly. We further characterized the structural
      and dynamic properties of the native state ensemble of IkappaBalpha and the
      stabilized mutants by H/(2)H exchange mass spectrometry and NMR. The solution
      experiments were complemented with molecular dynamics simulations to elucidate
      the microscopic origins of the stabilizing effect of the consensus substitutions,
      which can be traced to the fast conformational dynamics of the folded ensemble.

PMID- 17174336
TI  - Immunological aspects in the neurobiology of suicide: elevated microglial density
      in schizophrenia and depression is associated with suicide.
AB  - OBJECTIVES: Suicide has a high prevalence in patients with schizophrenia and
      affective disorder. Our recent postmortem study [Steiner J, Mawrin C, Ziegeler A,
      Bielau H, Ullrich O, Bernstein HG, Bogerts B. Distribution of HLA-DR-positive
      microglia in schizophrenia reflects impaired cerebral lateralization. Acta
      Neuropathologica (Berl) 2006;112:305-16.] revealed increased microglial densities
      in two schizophrenic patients who had committed suicide. Therefore, the
      hypothesis of microglial activation during acute psychosis was proposed.
      Alternatively, "suicide" could be a diagnosis-independent factor leading to
      microgliosis. METHODS: To clarify this question, microglial HLA-DR expression was
      analyzed by immunohistochemistry in the dorsolateral prefrontal cortex (DLPFC),
      anterior cingulate cortex (ACC), mediodorsal thalamus (MD) and hippocampus of 16
      schizophrenics, 14 depressed patients with affective disorder and 10 matched
      controls. A subgroup of six schizophrenics and seven patients with affective
      disorder who committed suicide was included. RESULTS: ANOVA revealed no effect of
      diagnosis on microglial density (DLPFC: P=0.469; ACC: P=0.349; MD: P=0.569;
      hippocampus: P=0.497). However, significant microgliosis was observed in the
      DLPFC (P=0.004), ACC (P=0.012) and MD (P=0.004) of suicide patients. A similar
      trend was seen in the hippocampus (P=0.057). CONCLUSION: In conclusion,
      immunological factors may play a hitherto underestimated role in suicide. First,
      microglial activation might be interpreted as a consequence of presuicidal
      stress. Second, one might speculate a causal link between microglial activation
      and suicidal behaviour, such as neuroendocrine factors, cytokines, and nitric
      oxide, which are released from microglial cells and are known to modulate
      noradrenergic or serotonergic neurotransmission and thus may trigger suicidality.

PMID- 17174337
TI  - Glycochenodeoxycholate (GCDC) inhibits cytokine induced iNOS expression in rat
      hepatocytes.
AB  - BACKGROUND: Although the accumulation of hydrophobic bile acid (e.g., glycine
      conjugated chenodeoxycholic acid, GCDC) is considered to be an important factor
      contributing to cholestatic liver dysfunction, its pathogenesis is poorly
      understood. The purpose of this study was to examine the effect of the bile salt
      GCDC on the regulation of iNOS expression, a key immune modulator during liver
      inflammation. MATERIALS AND METHODS: GCDC significantly decreased cytokine
      stimulated iNOS promoter activity, and both iNOS mRNA and protein expression.
      GCDC decreased iNOS promoter activity by preventing IkappaB degradation and
      inhibiting NF-kappaB DNA-binding activity. To explore the role of iNOS in bile
      salt induced apoptosis, we also examined the effect of NO on caspase-3 activity.
      RESULTS: GCDC strongly induced caspase-3 activity, and this increase was
      abrogated by both exogenous NO exposure and endogenous NO synthesis. Furthermore,
      adenoviral iNOS (AdiNOS) pre-treatment decreased acute cholestatic-induced liver
      injury in a rat bile duct ligation model. CONCLUSIONS: These findings indicate a
      novel signaling pathway where potentially toxic bile salts down-regulate hepatic
      iNOS expression. This blockade of the iNOS mediated antiapoptotic phenotype may
      have important implications in certain liver disorders.

PMID- 17174338
TI  - The effect of intraportal prostaglandin E1 on adhesion molecule expression,
      inflammatory modulator function, and histology in canine hepatic
      ischemia/reperfusion injury.
AB  - BACKGROUND: Prostaglandin E1 (PGE1) is known to protect the liver from I/R,
      however, the mechanism of cytoprotection is not well understood. This study
      investigates the effect of intraportal infusion of PGE1 in a warm liver
      ischemia/reperfusion (I/R) model on cytokines, adhesion molecules and liver
      structure. MATERIALS AND METHODS: Twenty dogs underwent laparotomy under general
      anesthesia. PGE1 (0.02 microg?kg?min) was perfused through the portal vein in the
      PGE1 group (n = 10), or a similar volume of Ringer's solution in the control
      group (n = 10) for 15 min. Liver ischemia was induced by hepatic artery and
      portal vein occlusion and PGE1 was infused via the portal vein for 60 min. The
      occlusion was released and PGE1 infusion recommenced for 30 min. Blood and liver
      biopsies were sampled at baseline, 60 min ischemia, and 30 min reperfusion and
      assessed for transaminases, cytokines, adhesion molecules, and electron
      microscopy. RESULTS: PGE1 infusion significantly reduced transaminases TNF-alpha,
      sICAM-1, sP-selectin, and sE-selectin on ischemia and reperfusion. PGE1 reduced
      hepatocytic degeneration, portal and central ICAM-1 expression, central and
      sinusoidal VCAM-1 expression, portal and central P-selectin expression, and
      portal and sinusoidal E-selectin expression on reperfusion. CONCLUSION:
      Intraportal PGE1 infusion reduced I/R injury and was associated with down
      regulation of ICAM-1, VCAM-1, P-selectin, and E-selectin on reperfusion.

PMID- 17174339
TI  - Prognostic scoring in patients with melanoma after adjuvant isolated limb
      perfusion.
AB  - BACKGROUND: The clinical course in melanoma is variable. The aim of the present
      study was to assess adjuvant isolated limb perfusion (ILP) efficacy using a
      surrogate comparison of observed survival versus Cochran-predicted survival.
      MATERIALS AND METHODS: All patients in a single university hospital with primary,
      non-ulcerated limb melanoma who had undergone adjuvant ILP over 10 years (1986
      1995) were studied. Clinical and pathological details including follow-up and
      survival were prospectively recorded in a national database. All patients were
      risk scored, as described by Cochran et al., to yield individual survival
      probability at the end of 3, 5 and 10 years and this was compared with observed
      survival at corresponding intervals. RESULTS: There were 85 patients who had
      adjuvant ILP for primary non-ulcerated limb melanoma. Of these, 14 deaths were
      observed (O) within the 10-year follow-up period. The Cochran score predicted (E)
      20 deaths within 10 years (O/E ratio 0.7). The O/E ratios for deaths in the 0 to
      3, 3 to 5, and 5 to 10 year intervals were 8/7.4, 5/6.0, and 1/6.5, respectively;
      prediction of late deaths tended to be overestimated. When patients were grouped
      by predicted 10-year mortality (<20%, 20-40%, >40%) the overestimation was found
      to occur mainly in the highest risk group: O/E ratios were 6/5.9, 6/8.4, and
      2/5.6, respectively (P = 0.10, Hosmer-Lemeshow test). CONCLUSION: The observed
      and expected survival in patients receiving adjuvant ILP at the end of 3 and 5
      years are comparable. The Cochran scoring system overestimated deaths during the
      5 to 10 year interval. It is not clear whether this observation is a consequence
      of ILP efficacy or inaccuracy of the Cochran score.

PMID- 17174340
TI  - Comparing knowledge and attitudes towards genetic testing in Parkinson's disease
      in an American and Asian population.
AB  - INTRODUCTION: Recent discoveries of disease-causing genes in Parkinson's disease
      (PD) have generated considerable interest regarding genetic testing in PD. The
      attitudes toward genetic testing are largely influenced by knowledge and
      preconceived notions. OBJECTIVE: We investigated the relationship between
      knowledge of and attitude towards predictive genetic testing of PD in two
      independent centers in America and Asia involving PD patients and caregivers.
      METHODS: In a prospective study involving 515 subjects comprising of PD patients
      and their caregivers in two independent centers in America and Asia, the level of
      knowledge about genetic testing and patients' attitudes towards such testing were
      evaluated using a standardized questionnaire. RESULTS: American PD patients had a
      higher level of knowledge of PD genetics than Asian PD (31.1% vs. 12.3%,
      p=0.0002). A greater number of American PD patients and caregivers reported a
      positive attitude towards the potential medical benefits of genetic testing
      compared to their Asian counterparts (85.4% vs. 42.2%, 92.2% vs. 32.1%,
      p<0.00005), but a more negative attitude towards potential compromise in getting
      health and life insurance (43.7% vs. 25.8%, p=0.0002). However, in the Asian
      cohort, multivariate analysis revealed that a high level of genetics knowledge
      was associated with a positive attitude response regarding the potential medical
      benefits of testing (p<0.0005), but a negative attitude towards compromises in
      healthcare and life insurance, getting a job and starting a family (p<0.0005).
      These associations were not observed amongst American subjects. CONCLUSIONS: The
      relationship between level of genetic knowledge and attitude towards potential
      risks and benefits of predictive genetic testing in PD was distinctly different
      in two independent, racially and culturally different PD populations and
      caregivers. These observations have clinical implications in the development of
      PD genetic counseling programs.

PMID- 17174341
TI  - Mechanisms by which acyclovir reduces the oxidative neurotoxicity and
      biosynthesis of quinolinic acid.
AB  - The concentration of the endogenous neurotoxin quinolinic acid (QA) is increased
      in the central nervous system of mice with herpes simplex encephalitis. We have
      previously shown that the antiherpetic agent acyclovir (AC) has the ability to
      reduce QA-induced neuronal damage in rat brain, by attenuating lipid
      peroxidation. The mechanism by which QA induces lipid peroxidation includes the
      enhancement of the iron (Fe)-mediated Fenton reaction and the generation of free
      radicals, such as the superoxide anion (O(2)(-)). Thus, the present study
      determined whether AC has the ability to reduce Fe(2+)-induced lipid
      peroxidation, O(2)(-) generation and QA-induced superoxide anion generation, and
      to bind free Fe. O(2)(-) and Fe(2+) are also cofactors of the enzymes,
      indoleamine-2,3-dioxygenase (IDO) and 3-hydroxyanthranilate-3,4-dioxygenase (3
      HAO) respectively. These enzymes catalyse steps in the biosynthesis of QA; thus,
      the effect of AC on their activity was also investigated. AC significantly
      attenuates Fe(2+)-induced lipid peroxidation and O(2)(-) generation. AC reduces
      O(2)(-) generation in the presence of QA and strongly binds Fe(2+) and Fe(3+). It
      also reduces the activity of both IDO and 3-HAO, which could be attributed to the
      superoxide anion scavenging and iron binding properties, respectively, of this
      drug.

PMID- 17174342
TI  - Development and sexual dimorphism of the pituitary gland.
AB  - The pituitary gland plays a central role in sexual development and brain
      function. Therefore, we examined the effect of age and gender on pituitary volume
      in a large sample of healthy children and adults. Volumetric magnetic resonance
      imaging (MRI) was conducted in one hundred and fifty four (77 males and 77
      females) healthy participants. Males were between the ages of 7 to 35 years
      (16.91+/-5.89 years) and females were 7 to 35 years of age (16.75+/-5.75 years).
      Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to
      21, 22 and older) and sex (male/female). Pituitary gland volume differed between
      sexes when comparing the age groups (F=3.55, df=2, 143, p=0.03). Females
      demonstrated larger pituitary glands than males in the age 14 to 17 year old
      groups (p=0.04). Young (19 years and under) and old (20 years and older) females
      demonstrated a correlation between pituitary volume and age. Males did not show
      this relationship. These findings provide additional evidence for gender
      differences in the normative anatomy of the pituitary and may have relevance for
      the study of various childhood onset neuropsychiatric disorders in which
      pituitary dysfunction has been implicated.

PMID- 17174343
TI  - Low-intensity pulsed ultrasound stimulates osteogenic differentiation in ROS
      17/2.8 cells.
AB  - There have been no studies investigating the effects of the mechanical
      stimulation provided by Low-intensity pulsed ultrasound (LIPUS) treatment on
      periodontal disease accompanying bone loss. LIPUS is known to accelerate
      mineralization and bone regeneration, but the precise cellular mechanism is
      unclear. Here, we investigated the effect of LIPUS on osteogenesis by examining
      the effect of LIPUS stimulation on cell proliferation, alkaline phosphatase
      (ALPase) activity, osteogenesis-related gene expression, and mineralized nodule
      formation in a rat osteosarcoma cell line. The cells were cultured in medium with
      or without the addition of LIPUS stimulation. The ultrasound signal consisted of
      1.5 MHz at an intensity of 30 mW/cm(2) for 20 min for all cultures. LIPUS
      stimulation did not affect the rate of cell proliferation. ALPase activity was
      increased at day 7 of culture after LIPUS stimulation. Real-time PCR analysis
      indicated that LIPUS significantly increased the expression of mRNA for the
      transcription factors Runx2, Msx2, Dlx5, and Osterix and for bone sialoprotein,
      whereas the mRNA expression of AJ18 was significantly reduced. The mineralized
      nodule formation and the calcium content in mineralized nodules were markedly
      increased on day 14 of culture after LIPUS stimulation. Our study demonstrates
      that LIPUS stimulation directly affects osteogenic cells, leading to mineralized
      nodule formation. In view of the widespread use of LIPUS for the clinical therapy
      of periodontal disease, it is likely that LIPUS has an important influence on key
      functional activities of osteoblasts in alveolar bone.

PMID- 17174344
TI  - Advanced glycation endproduct induces ROS accumulation, apoptosis, MAP kinase
      activation and nuclear O-GlcNAcylation in human cardiac myocytes.
AB  - Accumulation of advanced glycation endproduct (AGE) has been implicated in the
      pathogenesis of diabetic complications. However, the precise role and mechanism
      behind AGE-associated diabetic heart injury are not fully clear. This study was
      designed to evaluate the effect of AGE on accumulation of reactive oxygen species
      (ROS), apoptosis, mitogen-activated protein kinase (MAPK) activation and nuclear
      O-GlcNAcylation in fetal human cardiac myocytes. Myocytes were maintained for 24
      72 h in a defined culture medium containing high glucose, the AGE carbon
      precursor methylglyoxal (MG), and MG-AGE derived from MG and bovine serum albumin
      (BSA). Generation of ROS was detected by 5-(6)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate. Apoptosis was evaluated by caspase-3
      activity and quantitative DNA fragmentation. Both high glucose (25.5 mM) and MG
      (200 microM) significantly enhanced ROS and AGE formation with greater effects
      elicited by MG. Both high glucose and MG-AGE significantly facilitated apoptosis
      with a more predominant effect from MG-AGE. In addition, phosphorylation of MAPK
      cascade [extracellular signal-regulated kinase-1/2 (ERK1/2) and p38] and nuclear
      O-GlcNAcylation were enhanced in MG-AGE-treated myocytes, similar to those
      elicited by high glucose. MG-AGE-induced phosphorylation of ERK1/2 and p38 was
      nullified by neutralizing AGE with specific anti-AGE antibody but not nonspecific
      antiserum. Collectively, these results indicated that AGE or its precursor MG may
      trigger ROS generation, apoptosis, MAPK activation and nuclear O-GlcNAcylation in
      human cardiac myocytes, in a manner reminiscent of high extracellular glucose.

PMID- 17174345
TI  - Protective effects of EGCg or GCg, a green tea catechin epimer, against
      postischemic myocardial dysfunction in guinea-pig hearts.
AB  - The protective effects of (-)-epigallocatechin-3-gallate (EGCg) or the C-2
      epimer, (-)-gallocatechin-3-gallate (GCg), afforded by their antioxidative
      activity among green tea catechins were investigated in perfused guinea-pig
      Langendorff hearts subjected to ischemia and reperfusion. The recovery (%) of the
      left ventricular developed pressure from ischemia by reperfusion was 34.4% in the
      control, while in the presence of EGCg (3x10(-5) M) or GCg (3x10(-6) M, a more
      diluted concentration than that of EGCg), it led to a maximal increase of 78.4%
      or 76.2%, consistent with a significant preservative effect on the tissue level
      of ATP at the end of ischemia or reperfusion. In the perfused preparation of
      mitochondria, EGCg (10(-5) M) inhibited mitochondrial Ca(2+) elevation by changes
      in the Ca(2+) content or the acidification of perfusate, similarly to findings
      with cyclosporin A, a well known inhibitor of the mitochondrial permeability
      transition pore. By in vitro electron paramagnetic resonance (EPR), EGCg or GCg
      was found to directly quench the activity of active oxygen radicals, with the
      strongest activity in tea catechins. EGCg or GCg decreased the caspase-3 activity
      induced apoptosis. Therefore, it is concluded that the beneficial effects of EGCg
      or GCg play an important role in ischemia-reperfusion hearts in close relation
      with nitric oxide (NO), active oxygen radicals and biological redox systems in
      mitochondria.

PMID- 17174346
TI  - Heroin epidemics, treatment and ODE modelling.
AB  - The UN [United Nations Office on Drugs and Crime (UNODC): World Drug Report,
      2005, vol. 1: Analysis. UNODC, 2005.], EU [European Monitoring Centre for Drugs
      and Drug Addiction (EMCDDA): Annual Report,
      2005.http://annualreport.emcdda.eu.int/en/home-en.html.] and WHO [World Health
      Organisation (WHO): Biregional Strategy for Harm Reduction, 2005-2009. HIV and
      Injecting Drug Use. WHO, 2005.] have consistently highlighted in recent years the
      ongoing and persistent nature of opiate and particularly heroin use on a global
      scale. While this is a global phenomenon, authors have emphasised the significant
      impact such an epidemic has on individual lives and on society. National
      prevalence studies have indicated the scale of the problem, but the drug-using
      career, typically consisting of initiation, habitual use, a treatment-relapse
      cycle and eventual recovery, is not well understood. This paper presents one of
      the first ODE models of opiate addiction, based on the principles of mathematical
      epidemiology. The aim of this model is to identify parameters of interest for
      further study, with a view to informing and assisting policy-makers in targeting
      prevention and treatment resources for maximum effectiveness. An epidemic
      threshold value, R(0), is proposed for the drug-using career. Sensitivity
      analysis is performed on R(0) and it is then used to examine the stability of the
      system. A condition under which a backward bifurcation may exist is found, as are
      conditions that permit the existence of one or more endemic equilibria. A key
      result arising from this model is that prevention is indeed better than cure.

PMID- 17174347
TI  - Population models with singular equilibrium.
AB  - A class of models of biological population and communities with a singular
      equilibrium at the origin is analyzed; it is shown that these models can possess
      a dynamical regime of deterministic extinction, which is crucially important from
      the biological standpoint. This regime corresponds to the presence of a family of
      homoclinics to the origin, so-called elliptic sector. The complete analysis of
      possible topological structures in a neighborhood of the origin, as well as
      asymptotics to orbits tending to this point, is given. An algorithmic approach to
      analyze system behavior with parameter changes is presented. The developed
      methods and algorithm are applied to existing mathematical models of biological
      systems. In particular, we analyze a model of anticancer treatment with oncolytic
      viruses, a parasite-host interaction model, and a model of Chagas' disease.

PMID- 17174349
TI  - Oxygen delivery through capillaries.
AB  - During physical exertion the consumption rate increases and some cells suffer
      from the lack of oxygen. The time-wise evolution of hypoxia is analyzed
      mathematically under the condition the perfusion of each capillary is constant.
      The domain used contains multiple non-homogeneous capillaries of different solute
      out. Cells surrounding capillaries may consume or preserve more oxygen than are
      necessary at the beginning of new environment.

PMID- 17174348
TI  - Voltage noise influences action potential duration in cardiac myocytes.
AB  - Stochastic gating of ion channels introduces noise to membrane currents in
      cardiac muscle cells (myocytes). Since membrane currents drive membrane
      potential, noise thereby influences action potential duration (APD) in myocytes.
      To assess the influence of noise on APD, membrane potential is in this study
      formulated as a stochastic process known as a diffusion process, which describes
      both the current-voltage relationship and voltage noise. In this framework, the
      response of APD voltage noise and the dependence of response on the shape of the
      current-voltage relationship can be characterized analytically. We find that in
      response to an increase in noise level, action potential in a canine ventricular
      myocytes is typically prolonged and that distribution of APDs becomes more skewed
      towards long APDs, which may lead to an increased frequency of early after
      depolarization formation. This is a novel mechanism by which voltage noise may
      influence APD. The results are in good agreement with those obtained from more
      biophysically-detailed mathematical models, and increased voltage noise (due to
      gating noise) may partially underlie an increased incidence of early after
      depolarizations in heart failure.

PMID- 17174350
TI  - Stochastic models for the spread of HIV in a mobile heterosexual population.
AB  - An important factor in the dynamic transmission of HIV is the mobility of the
      population. We formulate various stochastic models for the spread of HIV in a
      heterosexual mobile population, under the assumptions of constant and varying
      population sizes. We also derive deterministic and diffusion analogues for these
      models, using a convenient rescaling technique, and analyze their stability
      conditions and equilibrium behavior. We illustrate the dynamic behavior of the
      models and their approximations via a range of numerical experiments.

PMID- 17174351
TI  - Steady-state solutions in mathematical models of atrial cell electrophysiology
      and their stability.
AB  - The steady states of the Fenton-Karma, the Courtemanche and the Nygren cell
      models were studied by determining the fixed points of the dynamical system
      describing their cell kinetics. The linear stability of the fixed points was
      investigated, as well as their response to external stimuli. Symbolic
      calculations were carried out as far as possible in order to prove the existence
      of these fixed points. In the Fenton-Karma model, a unique stable fixed point was
      found, namely the resting state. In contrast, the Courtemanche model had an
      infinite number of fixed points. A bifurcation diagram was constructed by
      classifying these fixed points according to a conservation law. Initial
      conditions were identified, for which the dynamical behavior of the cell was auto
      oscillatory. In its original formulation, the Nygren model had no fixed point.
      After having restored charge conservation, the system was found to have an
      infinite number of fixed points, resulting in a bifurcation diagram similar to
      that of the Courtemanche model. The approach proposed in this paper assists in
      the exploration of the high-dimensional parameter space of the cell models and
      the identification of the conditions leading to spontaneous pacemaker activity.

PMID- 17174352
TI  - A note on generation times in epidemic models.
AB  - The time between the infection of a primary case and one of its secondary cases
      is called a generation time. The distribution (and mean) of the generation times
      is derived for a rather general class of epidemic models. The relation to
      assumptions on distributions of latency times and infectious times or more
      generally on random time varying infectiousness, is investigated. Serial times,
      defined as the times between occurrence of observable events in the progress of
      an infectious disease (e.g., the onset of clinical symptoms), are also
      considered.

PMID- 17174353
TI  - Continuum description of a contact infection spread in a SIR model.
AB  - We consider the process of an epidemic spread in a population of individuals with
      low mobility within the SIR scheme. In a continuum limit such propagation
      mechanism is described by a non-linear reaction-diffusion equation with a
      diffusion coefficient being the function of the densities of susceptible. The
      traveling wave solution of the corresponding system of partial differential
      equations is obtained and analyzed. We show that the model allows for description
      of Kendall epidemic waves, and give the dependence of the infection wave's shape
      on the parameters of the system. An explicit calculation is done for realistic
      values of parameters obtained from field epidemiological data for a phocine
      distemper virus infection among harbor seals in 1988.

PMID- 17174354
TI  - New approaches to assessing the effects of mutagenic agents on the integrity of
      the human genome.
AB  - Heritable genetic alterations, although individually rare, have a substantial
      collective health impact. Approximately 20% of these are new mutations of unknown
      cause. Assessment of the effect of exposures to DNA damaging agents, i.e.
      mutagenic chemicals and radiations, on the integrity of the human genome and on
      the occurrence of genetic disease remains a daunting challenge. Recent insights
      may explain why previous examination of human exposures to ionizing radiation, as
      in Hiroshima and Nagasaki, failed to reveal heritable genetic effects. New
      opportunities to assess the heritable genetic damaging effects of environmental
      mutagens are afforded by: (1) integration of knowledge on the molecular nature of
      genetic disorders and the molecular effects of mutagens; (2) the development of
      more practical assays for germline mutagenesis; (3) the likely use of population
      based genetic screening in personalized medicine.

PMID- 17174355
TI  - Chromosome aberrations in Chinese hamster and human cells: a comparison using
      compounds with various genotoxicity profiles.
AB  - Chromosome aberrations (Cabs) can be induced in vitro by non-DNA damaging
      compounds, often associated with cytotoxicity and DNA synthesis inhibition, and
      under conditions that would not be relevant in vivo. Such misleading positive
      results are reported both in Chinese hamster cell lines and in human peripheral
      blood lymphocytes (HL). We assessed the response of HL to compounds with varied
      genetic toxicity profiles, all of which induced Cabs in CHO cells Seven of 10
      compounds were negative or equivocal in HL. Results in purified lymphocytes for
      four verified that the difference was not due to the presence of blood in
      cultures. Two compounds that were weakly positive in the Ames test and one that
      induced DNA adducts were negative or equivocal in the HL assay; their overall
      mutagenic potential in vivo is not clear. Of four Ames-negative compounds, three
      of which inhibited DNA synthesis in CHO cells, three were negative and one was
      equivocal in the HL assay. A potent Cab inducer, which also induced micronuclei
      in vivo (but was negative in the Ames test) was clearly positive in the HL assay.
      Two compounds were clearly positive in HL only when the mitotic indices (MI) were
      below 50% of control. These are genotoxic in other assays but our evidence
      suggests that Cab induction is related more to toxicity than to primary DNA
      damage. For this limited set of 10 compounds, HL were more likely than CHO cells
      to give negative or equivocal results. It is likely that more stringent
      checkpoint controls in human cells prevent damaged cells reaching mitosis, and
      may also influence the reported greater sensitivity to induction of aneuploidy
      and polyploidy of normal rodent compared with human cells. In the studies
      reported here, two strong inducers of polyploidy in CHO cells gave weaker
      increases in HL. Human lymphocytes have disadvantages as a routine screening
      assay (finding donors, known individual variability, increased time required and
      the inadequacy of the MI as a toxicity measure), but may be useful in follow-up
      testing to assess weight of evidence about genotoxic risk to humans, for
      compounds that are positive in the Chinese hamster cell Cabs assays.

PMID- 17174356
TI  - Differential cell cycle-specificity for chromosomal damage induced by merbarone
      and etoposide in V79 cells.
AB  - Merbarone, a topoisomerase II (topo II) inhibitor which, in contrast to
      etoposide, does not stabilize topo II-DNA cleavable complexes, was previously
      shown to be a potent clastogen in vitro and in vivo. To investigate the possible
      mechanisms, we compared the cell cycle-specificity of the clastogenic effects of
      merbarone and etoposide in V79 cells. Using flow cytometry and BrdU labeling
      techniques, etoposide was shown to cause a rapid and persistent G2 delay while
      merbarone was shown to cause a prolonged S-phase followed by a G2 delay. To
      identify the stages which are susceptible to DNA damage, we performed the
      micronucleus (MN) assay with synchronized cells or utilized a combination of BrdU
      pulse labeling and the cytokinesis-blocked MN assay with non-synchronized cells.
      Treatment of M phase cells with either agent did not result in increased MN
      formation. Etoposide but not merbarone caused a significant increase in MN when
      cells were treated during G2 phase. When treated during S-phase, both chemicals
      induced highly significant increases in MN. However, the relative proportion of
      MN induced by merbarone was substantially higher than that induced by etoposide.
      Both chemicals also caused significant increases in MN in cells that were treated
      during G1 phase. To confirm the observations in the MN assay, first division
      metaphases were evaluated in the chromosome aberration assay. The chromosomes of
      cells treated with merbarone and etoposide showed increased frequencies of both
      chromatid- and chromosome-type of aberrations. Our findings indicate that while
      etoposide causes DNA damage more evenly throughout the G1, S and G2 phases of the
      cell cycle, an outcome which may be closely associated with topo II-mediated DNA
      strand cleavage, merbarone induces DNA breakage primarily during S-phase, an
      effect which is likely due to the stalling of replication forks by inhibition of
      topo II activity.

PMID- 17174357
TI  - Ush1c216A knock-in mouse survives Katrina.
AB  - Usher syndrome is the most common cause of inherited deafness found in
      combination with blindness. All Usher patients suffer progressive retinitis
      pigmentosa, with the degree of hearing impairment and the presence or absence of
      vestibular function differing among subtypes. A cryptic splice site mutation
      (216G-->A) in exon 3 of the USH1C gene on chromosome 11p, which encodes a PDZ
      domain protein, harmonin, was found in Acadian Usher type IC patients in south
      Louisiana. In vitro analysis using constructs containing the mutant 216A and
      subsequent analysis of patient cell lines revealed a deletion of 35 bases in the
      transcript. In order to analyze the impact of this frame-shift mutation, we
      created a knock-in mouse model containing the human 216G-->A mutation. A
      targeting construct was made containing 5' and 3' homology arms, each 4kb in
      length, and a 650 base pair fragment containing exons 3 and 4 of human USH1C
      cloned from an Acadian patient homozygous for the 216A mutation. W4/129S6
      embryonic stem (ES) cells were electroporated with the targeting construct, and
      after 10 days of neomycin selection, clones were picked and screened by
      polymerase chain reaction (PCR) and Southern blot analysis for homologous
      recombination. Two positive clones for targeted insertion were microinjected into
      C57BL/6 blastocysts which were then transplanted into pseudo-pregnant females.
      Chimeras were bred with Cre recombinase-expressing mice for simultaneous deletion
      of the neomycin gene and germline transmission of the 216A allele. Homozygous
      Ush1c216A (216AA) mice are hyperactive, display circling and head tossing
      behavior, and do not have a Preyer reflex at 21-25 days old. RT-PCR analysis of
      the cochlea and retina from 216AA mice shows the same 35 base deletion
      characteristic of Usher IC patients.

PMID- 17174359
TI  - Chronic exposure to sublethal doses of radiation mimetic Zeocin selects for
      clones deficient in homologous recombination.
AB  - DNA double-strand breaks (DSBs) are highly toxic lesions leading to genome
      variability/instability. The balance between homologous recombination (HR) and
      non-homologous end-joining (NHEJ), two alternative DSB repair systems, is
      essential to ensure genome maintenance in mammalian cells. Here, we transfected
      CHO hamster cells with the pcDNA3.1/Zeo plasmid, and selected transfectants with
      Zeocin, a bleomycin analog which produces DSBs. Despite the presence of a Zeocin
      resistance gene in pcDNA3.1/Zeo, Zeocin induced 8-10 gamma-H2AX foci per cell.
      This shows that the Zeocin resistance gene failed to fully detoxify cells treated
      with Zeocin, and that during selection cells were submitted to a chronic
      sublethal DSB stress. Selected clones show decreases in both spontaneous and
      induced intrachromosomal HR. In contrast, in an in vitro assay, these clones show
      an increase in NHEJ products specific to the KU86 pathway. We selected cells, in
      the absence of pcDNA3.1/Zeo, with low and sublethal doses of Zeocin, producing a
      mean 8-10 gamma-H2AX foci per cell. Newly selected clones exhibited similar
      phenotypes: HR decrease accompanied by an increase in KU86-dependent NHEJ
      efficiency. Thus chronic exposure to sublethal numbers of DSBs selects cells
      whose HR versus NHEJ balance is altered. This may well have implications for
      radio- and chemotherapy, and for management of environmental hazards.

PMID- 17174358
TI  - Comparison of the genetic effects of equimolar doses of ENU and MNU: while the
      chemicals differ dramatically in their mutagenicity in stem-cell spermatogonia,
      both elicit very high mutation rates in differentiating spermatogonia.
AB  - Mutagenic, reproductive, and toxicity effects of two closely related chemicals,
      ethylnitrosourea (ENU) and methylnitrosourea (MNU), were compared at equimolar
      and near-equimolar doses in the mouse specific-locus test in a screen of all
      stages of spermatogenesis and spermiogenesis. In stem-cell spermatogonia (SG),
      ENU is more than an order of magnitude more mutagenic than MNU. During post-SG
      stages, both chemicals exhibit high peaks in mutation yield when differentiating
      spermatogonia (DG) and preleptotene spermatocytes are exposed. The mutation
      frequency induced by 75mgMNU/kg during this peak interval is, to date, the
      highest induced by any single-exposure mutagenic treatment - chemical or
      radiation - that allows survival of the exposed animal and its germ cells,
      producing an estimated 10 new mutations per genome. There is thus a vast
      difference between stem cell and differentiating spermatogonia in their
      sensitivity to MNU, but little difference between these stages in their
      sensitivity to ENU. During stages following meiotic metaphase, the highest
      mutation yield is obtained from exposed spermatids, but for both chemicals, that
      yield is less than one-quarter that obtained from the peak interval. Large-lesion
      (LL) mutations were induced only in spermatids. Although only a few of the
      remaining mutations were analyzed molecularly, there is considerable evidence
      from recent molecular characterizations of the marker genes and their flanking
      chromosomal regions that most, if not all, mutations induced during the peak
      sensitive period did not involve lesions outside the marked loci. Both ENU and
      MNU treatments of post-SG stages yielded significant numbers of mutants that were
      recovered as mosaics, with the proportion being higher for ENU than for MNU.
      Comparing the chemicals for the endpoints studied and additional ones (e.g.,
      chromosome aberrations, toxicity to germ cells and to animals, teratogenicity)
      revealed that while MNU is generally more effective, the opposite is true when
      the target cells are SG.

PMID- 17174361
TI  - A new animal welfare concept based on allostasis.
AB  - Animal welfare is an increasing issue of public concern and debate. As a result,
      many countries are reconsidering the way animal welfare is embedded in the
      legislation and rules for housing and care of animals. This requires general
      agreement of what animal welfare is. Unfortunately, the current science of animal
      welfare is less scientific than what has been claimed. In our view, it is overly
      guided by anthropocentric thinking about how animals ought to be handled and
      neglects the latest concept of physiology: 'The Allostasis Concept'. Allostasis,
      which means stability through change, has the potential to replace homeostasis as
      the core model of physiological regulation. Not constancy or freedoms, but
      capacity to change is crucial to good physical and mental health and good animal
      welfare. Therefore, not homeostasis but allostasis is at the basis of our new
      animal welfare concept. This paper is aimed at a broader scientific discussion of
      animal welfare that includes knowledge from the latest scientific developments in
      neurobiology and behavioral physiology, and generates views that are extremely
      relevant for the animal welfare discussion.

PMID- 17174360
TI  - A pharmacophore derived phenytoin analogue with increased affinity for slow
      inactivated sodium channels exhibits a desired anticonvulsant profile.
AB  - Phenytoin (DPH) is a clinically useful sodium (Na) channel blocker with efficacy
      against partial and generalized seizures. We have developed a novel hydantoin
      compound (HA) using comparative molecular field analysis (CoMFA) and evaluated
      its effects on hNa(v)1.2 channels. Both DPH and HA demonstrated affinity for
      resting (K(r)=13.9microM for HA, K(r)=464microM for DPH) and slow inactivated
      channels (K(I)=975nM for HA, K(I)=20.6microM for DPH). However, HA also exhibited
      an affinity for fast inactivated channels (K(I)=2.5microM) and shifted the V(1/2)
      for activation in the depolarizing direction. Furthermore, HA exhibited profound
      use dependent block at both 5 and 10Hz stimulation frequencies. In the 6Hz
      seizure model (32mA) HA had an ED(50) of 47.1mg/kg and a TD(50) of 131mg/kg
      (protective index (PI)=2.8). In comparison, the ED(50) for DPH was approximately
      27.5mg/kg with a TD(50) of 35.6mg/kg (PI approximately 1.3). These findings
      provide evidence for the utility of CoMFA in the design of novel anticonvulsants
      and support the hypothesis that states selectivity plays an important role in
      achieving optimal protection with minimal side effects.

PMID- 17174362
TI  - The relationship between basal level of anxiety and the affective response to
      inflammation.
AB  - Pain is a multidimensional experience and is modulated by a number of factors.
      One such factor that plays a critical role in pain modulation is anxiety.
      However, the influence of individual differences in anxiety on higher order pain
      processing in rodents remains unclear. Therefore, the purpose of this study was
      to identify animals that have baseline levels of high and low anxiety using the
      elevated plus maze and then measure pain threshold and place escape/avoidance
      responding (a measure of pain affect) in the animals. As expected, there was a
      range of baseline behavior in the elevated plus maze that was used to separate
      animals into high and low anxiety groups. Following carrageenan injection, both
      groups of animals developed a similar degree of mechanical hypersensitivity and
      both groups showed similar place escape/avoidance behavior. These findings
      suggest that individual differences in baseline anxiety levels do not
      significantly contribute to the development of mechanical sensitivity and do not
      modulate higher order pain processing related to pain affect and motivation.

PMID- 17174363
TI  - Cloning and characterization of a Nicotiana tabacum methylputrescine oxidase
      transcript.
AB  - The oxidative deamination of N-methylputrescine is an essential step in both
      pyridine and tropane alkaloid biosynthesis. Reverse genetic approaches have not
      resulted in the cloning of a methylputrescine oxidase gene (MPO). However, we
      have used a homology-based approach to clone a full-length tobacco MPO1 cDNA. The
      MPO1 gene is part of a small multigene family comprised of approximately six
      members. MPO1-like transcript levels increased in roots that were either deprived
      of auxin or treated with methyl jasmonic acid. Similar to other known nicotine
      biosynthetic genes in domesticated tobacco, MPO1-like mRNA levels were lower in
      roots with the mutant a and b alleles. The MPO1 protein was expressed in bacteria
      as a recombinant Thioredoxin-His(6)-MPO1 fusion protein. The recombinant MPO1
      protein utilized N-methylputrescine more efficiently than other diamines.
      Therefore, the kinetic properties of the MPO1 enzyme may play an important role
      in determining the pyridine alkaloid profiles observed in tobacco roots.

PMID- 17174364
TI  - Acridone and furoquinoline alkaloids from Teclea gerrardii (Rutaceae:
      Toddalioideae) of southern Africa.
AB  - The combined hexane/CH(2)Cl(2) extract of the stem bark of Teclea gerrardii
      (Rutaceae: Toddalioideae) has yielded two acridone alkaloids, 3-hydroxy-1-methoxy
      N-methylacridone (tegerrardin A) (1) and 3-hydroxy-N-methyl-1-(gamma,gamma
      dimethylallyloxy)acridone (tegerrardin B) (2), three known acridones (3-5), two
      known furoquinolines (6,7), and the acridone precursor tecleanone (8). Arborinine
      (3) and evoxine (6) displayed moderate antiplasmodial activity against the CQS
      D10 strain of Plasmodium falciparum, with IC(50) values of 12.3 and 24.5 microM,
      respectively.

PMID- 17174365
TI  - Clinical, histopathological and immunophenotypical findings in five horses with
      cutaneous malignant lymphoma.
AB  - This study documents the clinical, histopathological, immunohistochemical and
      flow-cytometric findings in five horses with cutaneous non-epidermotropic
      malignant lymphoma (ML). The median survival time after discovery of the first
      subcutaneous nodules was 3.8 years (range 2-5 years: n=4). Histologically, the
      cutaneous ML had a pleiomorphic structure and contained a mixture of large
      reticulo-endothelial cells, medium-large sized lymphoid cells with a rounded
      nucleus and small nucleoli, many medium sized lymphoid cells with irregular
      nuclei, and some small lymphoid cells. Immunohistochemically (IHC) the lymphoid
      cells were positive for the pan-T-lymphocyte marker CD3 but negative for the B
      lymphocyte markers CD21 and kappa and lambda immunoglobulin light chains.
      Although routine haematological examination revealed no abnormalities in the
      horses with cutaneous ML, changes in the peripheral blood lymphocyte population
      were apparent flow-cytometrically. Compared to clinically healthy horses, a
      decreased total percentage of cells was recorded in the lymphocyte gate. In three
      horses with cutaneous ML, an increase in CD4 positive cells was noticed in the
      monocyte gate. Flow-cytometric analysis of tumour cells collected by fine needle
      aspiration (FNA) suggested that the cutaneous MLs consisted primarily of CD4 and
      CD8 positive T-lymphocytes. The results were compared to those of a monomorphic
      multicentric T- and a monomorphic multicentric B-cell lymphoma. The results of
      immunohistochemistry and flow-cytometry were largely but not completely in
      accordance. In conclusion, the results of this study suggest that cutaneous non
      epitheliotropic malignant lymphomas in the horse are of T-cell origin and that,
      after improvement of its accuracy, flow cytometric analysis of FNAs might become
      a useful aid to rapid tumour identification.

PMID- 17174367
TI  - 4,5-Epoxycholestane-3,6-diols: templates for generating the full set of eight
      cholestane-3,5,6-triol stereoisomers in multigram scales, but not for a
      cholestane-3,4,6-triol.
AB  - Cholestane-3beta,5alpha,6beta-triol is an extensively studied biologically
      important oxysterol. The full set of eight cholestane-3,5,6-triol stereoisomers
      was synthesised in diastereomerically pure forms by the stereoselective cleavage
      of eight diastereomerically pure 4,5-epoxycholestane-3,6-diols with LiAlH4, in
      high yields on multigram scales and without chromatography for most of them.
      However, applying various reportedly successful combinations of a hydride donor
      and a Lewis acid to the same substrates under a variety of conditions failed to
      generate a single unsubstituted cholestane-3,4,6-triol. The products of the eight
      cholestane-3,5,6-triol stereoisomers will serve as a good probe in the study of
      biological functions of oxysterols in a biological process.

PMID- 17174366
TI  - Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is
      anti-apoptotic.
AB  - Thyroid hormone (l-thyroxine, T(4), or 3,5,3'-triiodo-l-thyronine, T(3))
      treatment of human papillary and follicular thyroid cancer cell lines resulted in
      enhanced cell proliferation, measured by proliferating cell nuclear antigen
      (PCNA). Thyroid hormone also induced activation of the Ras/MAPK (ERK1/2) signal
      transduction pathway. ERK1/2 activation and cell proliferation caused by thyroid
      hormone were blocked by an iodothyronine analogue, tetraiodothyroacetic acid
      (tetrac), that inhibits binding of iodothyronines to the cell surface receptor
      for thyroid hormone on integrin alphaVbeta3. A MAPK cascade inhibitor at MEK, PD
      98059, also blocked hormone-induced cell proliferation. We then assessed the
      possibility that thyroid hormone is anti-apoptotic. We first established that
      resveratrol (10 microM), a pro-apoptotic agent in other cancer cells, induced p53
      dependent apoptosis and c-fos, c-jun and p21 gene expression in both papillary
      and follicular thyroid cancer cells. Induction of apoptosis by the stilbene
      required Ser-15 phosphorylation of p53. Resveratrol-induced gene expression and
      apoptosis were inhibited more than 50% by physiological concentrations of T(4).
      T(4) activated MAPK in the absence of resveratrol, caused minimal Ser-15
      phosphorylation of p53 and did not affect c-fos, c-jun and p21 mRNA abundance.
      Thus, plasma membrane-initiated activation of the MAPK cascade by thyroid hormone
      promotes papillary and follicular thyroid cancer cell proliferation in vitro.

PMID- 17174368
TI  - Drug resistance in tuberculosis--a reinfection model.
AB  - There is increasing recognition that reinfection is an important component of TB
      transmission. Moreover, it has been shown that partial immunity has significant
      epidemiological consequences, particularly in what concerns disease prevalence
      and effectiveness of control measures. We address the problem of drug resistance
      as a competition between two types of strains of Mycobacterium tuberculosis:
      those that are sensitive to anti-tuberculosis drugs and those that are resistant.
      Our objective is to characterise the role of reinfection in the transmission of
      drug-resistant tuberculosis. The long-term behaviour of our model reflects how
      reinfection modifies the conditions for coexistence of sensitive and resistant
      strains. This sets the scene for discussing how strain prevalence is affected by
      different control strategies. It is shown that intervention effectiveness is
      highly sensitive to the baseline epidemiological setting.

PMID- 17174369
TI  - Metabolic differences between two dimethylthioarsenicals in rats.
AB  - Thioarsenicals are newly found arsenic metabolites in man and animals, and also
      in marine organisms. Dimethylmonothioarsinic acid (DMMTA(V)) and
      dimethyldithioarsinic acid (DMDTA(V)) are the only two thioarsenic metabolites
      detected in man and/or animals. However, their toxicological and biological
      significance is not known yet. The present study was performed to gain an insight
      into the significance of DMMTA(V) and DMDTA(V) in the metabolism of arsenic. The
      two thioarsenicals were synthesized chemically and injected intravenously into
      rats at the dose of 0.5 mg As/kg body weight. The distributions of arsenic in
      organs/tissues and body fluids were determined at 10 min and 12 h after the
      injection, and arsenic in liver and kidney supernatants, urine, plasma and red
      blood cell (RBC) lysates was subjected to speciation analysis by HPLC-ICP MS on a
      gel filtration GS 220 HQ column. Although both thioarsenicals are pentavalent
      arsenicals, they were distributed in organs/tissues and body fluids differently
      from the corresponding non-thiolated pentavalent arsenicals, and also from each
      other. Namely, DMMTA(V) was first found in organs/tissues at 10 min, and then
      redistributed and retained mostly in RBCs at 12 h, as in the case of trivalent
      dimethylarsinous acid (DMA(III)). On the other hand, although DMDTA(V) was also
      found in organs/tissues at 10 min, it had been efficiently excreted in urine in
      its intact form at 12 h. Thus, DMMTA(V) was unexpectedly distributed in and taken
      up by organs/tissues in a manner similar to DMA(III) rather than DMA(V), whereas
      DMDTA(V) was distributed similarly to DMA(V) as expected, but was much more
      efficiently excreted in urine.

PMID- 17174371
TI  - Effects of brefeldin A on the localization of Tobamovirus movement protein and
      cell-to-cell movement of the virus.
AB  - It has been demonstrated that the subcellular location of Tobamovirus movement
      protein (MP) which was fused with green fluorescent protein (MP:GFP) changed
      during the infection process. However, the intracellular route through which MP
      is transported and its biological meaning are still obscure. Treatment with
      brefeldin A (BFA), which disrupts ER-to-Golgi transport, inhibited the formation
      of irregularly shaped and filamentous structures of MP. In this condition, MP was
      still targeted to plasmodesmata in leaf cells. Furthermore, the viral cell-to
      cell movement was not inhibited by BFA treatment. These data indicated that the
      targeting of viral replication complexes (VRCs) to plasmodesmata is mediated by a
      BFA-insensitive pathway and that the ER-to-Golgi transport pathway is not
      involved in viral intercellular movement.

PMID- 17174372
TI  - A reduction in selective immune pressure during the course of chronic hepatitis C
      correlates with diminished biochemical evidence of hepatic inflammation.
AB  - It is considered that selection pressure exerted by the host immune response
      during early HCV infection might influence the outcome of that infection
      particularly as it relates to persistence or clearance of the agent. However, it
      is unclear whether positive selection pressure plays a role in determining the
      severity of hepatitis C during the course of persistent HCV infection. To address
      the evolutionary mechanism by which HCV escapes from the host immune response and
      to assess the relationship between viral evolution and hepatic inflammation, we
      determined 57 sequences (3-5 serial samples per patient) from 5 individuals with
      persistent HCV infection of genotype 1a who were under long-term follow-up
      ranging from 15.6 to 21.6 years. We applied a novel method to estimate serial
      alternations of selective pressure against the HCV enveloped region and compared
      this to fluctuation in transaminase level over time. Positive selection pressure
      was reduced over time postinfection, as evidenced by a reduction in nonsynonymous
      substitutions in the later phase of infection. Furthermore, serum transaminase,
      as a measure of inflammatory necrosis of hepatocytes, was reduced in parallel
      with decreased positive selection pressure. These results suggest that during
      persistent HCV infection, the virus faces diminished immune pressure over time,
      either from mutation to an immune resistant sequence or from immunologic
      exhaustion, and that this diminished immune attack is reflected in diminished
      inflammatory activity. This observation may be applicable to other viruses
      characterized by a slow rate of disease progression.

PMID- 17174373
TI  - AcMNPV ORF38 protein has the activity of ADP-ribose pyrophosphatase and is
      important for virus replication.
AB  - The ORF38 of Autographa californica multiple nucleopolyhedrovirus (AcMNPV), or
      AcORF38, contains a conserved motif of Nudix (nucleotide diphosphate X)
      superfamily. It has the highest homology with ADP-ribose pyrophosphatase
      (ADPRase), a subfamily of Nudix pyrophosphatase. In the current study,
      recombinant AcORF38 protein was prepared and shown to have ADPRase activity, with
      a Km of 204 microM, and K(cat) of 6.96 s(-1) at pH 8.0 and 5 mM MgCl2. The
      transcription of AcORF38 was detected 2 h postinfection, and lasted until the
      late stage. An orf38 gene-deleted mutant virus, vAcGFP-Delta38, was constructed.
      Although it produced progeny virus, the yield of extracellular virus was less
      than 1% of the wild-type virus. The activity of viral very late gene promoter was
      also greatly reduced in vAcGFP-Delta38-infected cells as indicated by the
      expression of green fluorescence protein gene driven by polyhedrin promoter. The
      mutant phenotype was rescued by co-transfection with an AcORF38-expressing
      plasmid. These results suggest that AcORF38 plays an important role in virus
      replication, although the detail is to be elucidated.

PMID- 17174370
TI  - Pancreatic cancer: pathogenesis, prevention and treatment.
AB  - Pancreatic cancer is the fourth leading cause of cancer death in the United
      States with a very low survival rate of 5 years. To better design new preventive
      and/or therapeutic strategies for the fight against pancreatic cancer, the
      knowledge of the pathogenesis of pancreatic cancer at the molecular level is very
      important. It has been known that the development and the progression of
      pancreatic cancer are caused by the activation of oncogenes, the inactivation of
      tumor suppressor genes, and the deregulation of many signaling pathways among
      which the EGFR, Akt, and NF-kappaB pathways appear to be most relevant.
      Therefore, the strategies targeting EGFR, Akt, NF-kappaB, and their downstream
      signaling could be promising for the prevention and/or treatment of pancreatic
      cancer. In this brief review, we will summarize the current knowledge regarding
      the pathogenesis, prevention, and treatment of pancreatic cancer.

PMID- 17174374
TI  - Ventral extra-striate cortical areas are required for optimal orientation
      averaging.
AB  - We examined the ability of a previously well-studied patient with visual agnosia
      to compute the average orientation of elements in visual displays. In a
      structural MRI study, we show that the lesion is likely to involve a variety of
      ventral extra-striate areas, including V2, V3 and V4; however, the lesion does
      not extend dorsally. Subsequently we show that some ability to compute average
      orientation is spared, though there are limitations on the ability to scale the
      averaging process as a function of the numbers of elements. The results suggest
      that some aspects of orientation averaging can be accomplished in spared regions
      of V1 but flexible averaging requires ventral extra-striate cortex.

PMID- 17174375
TI  - The utility of surface reflectance for the recognition of upright and inverted
      faces.
AB  - The variation among faces can be partitioned into two sources: (a) shape and (b)
      surface reflectance. To compare the utility of shape and reflectance for face
      recognition, we created two sets of faces, with individual exemplars differing
      only by shape in one set and only by reflectance in the other set. Grayscale and
      full color versions of the stimuli were used in separate experiments; the
      physical variation between exemplars was equated across the two sets with the
      grayscale but not the full color stimuli. Subjects performed a matching task in
      which both the target and distractor were drawn from the same set, so that only
      shape or only reflectance information could be used to perform the task. With the
      grayscale stimuli, performance was better in the shape condition, but with the
      color stimuli, performance was better in the reflectance condition. Inversion of
      the faces disrupted performance with the shape and reflectance sets about
      equally, suggesting that the inversion effect is not caused specifically by the
      spacing of facial features, or even by shape information more generally. These
      results provide evidence that facial identity is a function of reflectance as
      well as shape, and place important constraints on explanations of why inversion
      impairs face recognition.

PMID- 17174376
TI  - Application of video-based technology for the simultaneous measurement of
      accommodation and vergence.
AB  - Accommodation and vergence are two ocular motor systems that interact during
      binocular vision. Independent measurement of the response dynamics of each system
      has been achieved by the application of optometers and eye trackers. However,
      relatively few devices, typically earlier model optometers, allow the
      simultaneous assessment of accommodation and vergence. In this study we describe
      the development and application of a custom designed high-speed digital
      photorefractor that allows for rapid measures of accommodation (up to 75Hz). In
      addition the photorefractor was also synchronized with a video-based stereo eye
      tracker to allow a simultaneous measurement of accommodation and vergence.
      Analysis of accommodation and vergence could then be conducted offline. The new
      instrumentation is suitable for investigation of young children and could be
      potentially used for clinical populations.

PMID- 17174377
TI  - Discolouration in potable water distribution systems: a review.
AB  - A large proportion of the customer contacts that drinking water supply companies
      receive stem from the occurrence of discoloured water. Currently, such complaints
      are dealt with in a reactive manner. However, water companies are being driven to
      implement planned activities to control discolouration prior to contacts
      occurring. Hence improved understanding of the dominant processes and predictive
      and management tools are needed. The material responsible for discolouration has
      a variety of origins and a range of processes and mechanisms may be associated
      with its accumulation within distribution systems. Irrespective of material
      origins, accumulation processes and mechanisms, discolouration events occur as a
      result of systems changes leading to mobilisation of the accumulations from
      within the network. Despite this conceptual understanding, there are very few
      published practicable tools and techniques available to aid water companies in
      the planned management and control of discolouration problems. Two recently
      developed and published, but different approaches to address this are reviewed
      here: the PODDS model which was developed to predict levels of turbidity as a
      result of change in hydraulic conditions, but which is semi-empirical and
      requires calibration; and the resuspension potential method which was developed
      to directly measure discolouration resulting from a controlled change in
      hydraulic conditions, providing a direct assessment of discolouration risk,
      although intrinsically requiring the limited generation of discoloured water
      within a live network. Both these methods support decision making on the need for
      maintenance operations. While risk evaluation and implementation of appropriate
      maintenance can be implemented to control discolouration risk, new material will
      continue to accumulate and hence an ongoing programme of maintenance is required.
      One sustainable measure to prevent such re-accumulation of material is the
      adoption of a self-cleaning threshold, an hydraulic force which a pipe
      experiences on a regular basis that effectively prevents the accumulation of
      material. This concept has been effectively employed for the design of new
      networks in the Netherlands. Alternatively, measures could be implemented to
      limit or prevent particles from entering or being generated within the network,
      such as by improving treatment or preventing the formation of corrosion by
      products through lining or replacing ferrous pipes. The cost benefit of such
      capex investment or ongoing opex is uncertain as the quantification and relative
      significance of factors possibly leading to material accumulation are poorly
      understood. Hence, this is an area in need of significant further practical
      research and development.

PMID- 17174378
TI  - Novel amidino-substituted benzimidazoles: synthesis of compounds and inhibition
      of dipeptidyl peptidase III.
AB  - Dipeptidyl peptidase III (DPP III), also known as enkephalinase B, is a zinc
      hydrolase with an indicated role in the mammalian pain modulatory system. In
      order to find a potent antagonist of this enzyme, we synthesized and screened the
      effect of a small set of benzimidazole derivatives on its activity. To improve
      the inhibitory potential, a cyclobutane ring was introduced as rigid conformation
      support to the diamidino substituted dibenzimidazoles. Two such compounds (1' and
      4') from the group of cyclobutane derivatives containing amidino-substituted
      benzimidazole moieties, obtained by photochemical cyclization in water and by
      respecting rules of the "green chemistry" approach, were found to be strong DPP
      III inhibitors, with IC(50) value below 5 microM. Compound 1' displayed time
      dependent inhibition towards human DPP III, characterized by the second-order
      rate constant of 6924+/-549 M(-1)min(-1) (K(i)=0.20 microM). The peptide
      substrate valorphin protected the enzyme from inactivation by 1'.

PMID- 17174379
TI  - Dechlorination after thermal treatment of a TCE-contaminated aquifer: laboratory
      experiments.
AB  - A microcosm study was conducted to evaluate dechlorination of trichloroethene
      (TCE) to ethene and survival of dechlorinating bacteria after a thermal treatment
      in order to explore the potential for post-thermal bioremediation. Unamended
      microcosms containing groundwater and aquifer material from a contaminated site
      dechlorinated TCE to cis-1,2-dichloroethene (cDCE), while lactate-amended
      microcosms dechlorinated TCE to cDCE or ethene. A thermal treatment was simulated
      by heating a sub-set of microcosms to 100 degrees C for 10d followed by cooling
      to 10 degrees C over 150 d. The heated microcosms demonstrated no dechlorination
      when unamended. However, when amended with lactate, cDCE was produced in 2 out of
      6 microcosms within 300 d after heating. Dechlorination of TCE to cDCE thus
      occurred in fewer heated (2 out of 12) than unheated (10 out of 12) microcosms.
      In unheated microcosms, the presence of dechlorinating microorganisms, including
      Dehalococcoides, was confirmed using nested PCR of 16S rRNA genes. Dechlorinating
      microorganisms were detected in fewer microcosms after heating, and
      Dehalococcoides were not detected in any microcosms after heating. Dechlorination
      may therefore be limited after a thermal treatment in areas that have been heated
      to 100 degrees C. Thus, inflow of groundwater containing dechlorinating
      microorganisms and/or bioaugmention may be needed for anaerobic dechlorination to
      occur after a thermal treatment.

PMID- 17174380
TI  - Anthropogenic nutrient sources and loads from a Mediterranean catchment into a
      coastal lagoon: Mar Menor, Spain.
AB  - The Mar Menor is a coastal lagoon increasingly threatened by urban and
      agricultural pressures. The main watercourse draining into the lagoon is the
      Rambla del Albujon. A fortnightly campaign carried out over one annual cycle
      enabled us to characterize the treated urban sewage effluents and agricultural
      sources which contribute to the nutrient fluxes in the watercourse. Multivariate
      analysis provided information for establishing chemical signatures and for
      assessing the relative influence of the various sources on the water quality at
      the outlet. Mass balances were used to examine net gains and losses, and cross
      correlations with rainfall to analyze climatic influence and control factors in
      the trends of the nutrient flux. The rainfall pattern was significantly cross
      correlated with nitrate and phosphorus fluxes from agricultural sources, while
      fluctuations in the resident population explained the phosphorus flux trend in
      urban sources. 50% of dissolved inorganic nitrogen was from agricultural sources,
      while 70% of total phosphate and 91% of total organic carbon were from urban
      point sources. The net amounts of all the nutrients fell as a result of plant
      uptake and/or denitrification in the channel. The control of urban point sources
      (phosphorus-enriched) is suggested as a promptly action for improving the health
      of the coastal lagoon.

PMID- 17174381
TI  - Haplotype analysis can provide improved clinical information than single genotype
      analysis.

PMID- 17174382
TI  - Superior pubic rami resection for isolated recurrent uterine cancer.

PMID- 17174383
TI  - Prognostic significance of iNOS in epithelial ovarian cancer.
AB  - OBJECTIVE: To study the association of inducible nitric oxide synthase (iNOS)
      expression with clinicopathological factors and prognosis in epithelial ovarian
      cancer. METHODS: The study included 301 patients with primary epithelial ovarian
      cancer. iNOS expression was evaluated by immunohistochemistry using a mouse
      monoclonal antibody. RESULTS: iNOS positivity was observed as granular deposits
      in the cancer cell cytoplasm. The mean percentage of iNOS-positive cells was 50%
      in primary tumors (n=301), and 62% in metastatic lesions (n=43). iNOS expression
      correlated significantly with histological subtype of the tumor, as high (> 70%)
      iNOS expression was observed in mucinous tumors (p=0.009). Poorly differentiated
      tumors showed a tendency to low (< or = 70%) iNOS expression but without
      statistical significance. Low iNOS expression associated also significantly with
      large primary residual tumor (p=0.007) and tumor recurrence (p=0.04). The 10-year
      prognosis of the patients with high iNOS expression was better in disease-related
      survival (DRS) (p=0.009). However, in multivariate analysis only FIGO stage,
      primary residual tumor, and grade of the tumor were independent prognostic
      factors for DRS, but not the iNOS expression. CONCLUSIONS: A major proportion of
      human epithelial ovarian cancers expressed iNOS. The positive expression was an
      indicator of better disease-related survival. However, iNOS positivity could not
      overcome the importance of clinicopathological factors in prediction of
      prognosis.

PMID- 17174384
TI  - Curcumin enhances Apo2L/TRAIL-induced apoptosis in chemoresistant ovarian cancer
      cells.
AB  - OBJECTIVE: Curcumin, the active component of turmeric (Curcuma longa), exhibits
      growth inhibitory activity against prostate, colon, and breast cancer; however,
      the effect of curcumin on ovarian cancer cells is not known. We hypothesized that
      curcumin could induce cell death in ovarian cancer cells, and enhance apoptosis
      induced by tumor necrosis factor-related apoptosis inducing Apo2 ligand/TRAIL.
      METHODS: Chemoresistant ovarian cancer cell lines SKOV3 and ES-2 were used. The
      cytotoxic effect of curcumin, Apo2L/TRAIL, and curcumin+Apo2L/TRAIL in
      combination was determined by sulforhodamine assay. Apoptotic fraction was
      determined by staining cells with propidium iodide followed by analysis of the
      sub-G0 DNA content of cells by flow cytometry. Caspase activation was determined
      by immunoblotting. RESULTS: Curcumin alone had a cytotoxic effect in cisplatin
      resistant cells at 25 microM. Curcumin at low doses (5-15 microM) or Apo2L/TRAIL
      alone was not significantly cytotoxic to the cell lines tested. Preincubating
      cells with curcumin at low doses prior to treating with Apo2L/TRAIL resulted in
      markedly enhanced cell death. The combined treatment of curcumin and Apo2L/TRAIL
      resulted in activation of both the extrinsic, receptor-mediated apoptotic pathway
      (cleavage of caspase-8) and the intrinsic, mitochondria-mediated apoptotic
      pathway (cleavage of caspase-9). CONCLUSIONS: Combined curcumin and Apo2L/TRAIL
      treatment results in enhanced induction of apoptotic cell death. Because curcumin
      and Apo2L/TRAIL together can activate both the extrinsic and intrinsic pathways
      of apoptosis, they may circumvent chemoresistance to conventional
      chemotherapeutic agents.

PMID- 17174385
TI  - Effect of the flavonoid, oroxylin A, on transient cerebral hypoperfusion-induced
      memory impairment in mice.
AB  - Oroxylin A is a flavonoid compound that is found in the root of Scutellaria
      baicalensis Georgi. The aim of this study was to determine the effects of
      oroxylin A on memory impairment induced by transient bilateral common carotid
      artery occlusion (2VO) in mice. The ameliorating effect of oroxylin A on memory
      impairment was investigated using a passive avoidance task, the Y-maze task, and
      the Morris water maze task in mice. Oroxylin A was found to significantly reverse
      2VO-induced cognitive impairments in the passive avoidance and Y-maze tasks in a
      dose dependant manner (P<0.05). Moreover, oroxylin A (5 mg/kg, p.o.) shortened
      the escape-latency and prolonged swimming times in the target quadrant during the
      probe trial in the Morris water maze task (P<0.05). Histochemical and
      immunohistochemical studies showed that the number of Nissl bodies and OX-42
      positive cells in the hippocampal CA1 and dentate gyrus regions were attenuated
      by oroxylin A. Moreover, phosphorylated cAMP response element-binding protein
      (CREB) and brain derived neurotrophic factor (BDNF) positive cell numbers were
      markedly increased in animals treated with oroxylin A than in untreated 2VO
      controls. These results suggest that oroxylin A dramatically attenuates the
      memory impairment induced by 2VO, and that this effect may be mediated by the
      neuroprotective effects of oroxylin A as supported oroxylin A induced reductions
      in activated microglia and increases in BDNF expression and CREB phosphorylation.

PMID- 17174386
TI  - Intra-hippocampal inhibition of protein kinase AII attenuates morphine-induced
      conditioned place preference.
AB  - Morphine and other drugs of abuse modulate protein kinase A (PKA) signaling
      within the mesolimbic reward pathway. Using a balanced conditioned place
      preference (CPP) paradigm, we studied the possible involvement of protein kinase
      AII (PKA II) on the acquisition, expression and consolidation of morphine place
      conditioning in male Wistar rats. Subcutaneous administration of various doses of
      morphine sulfate (1-9 mg/kg) induced CPP in a dose-dependent manner. H-89, a
      selective PKA II inhibitor, was administered into CA1 region of the hippocampus
      at 1, 2.5 and 5 microM/rat. Using a 3-day schedule of conditioning, it was found
      that the H-89 did not produce a significant place preference or place aversion. H
      89 (1, 2.5 and 5 microM/rat) significantly reduced the time spent by rats in the
      morphine compartment when given immediately after each conditioning session
      (consolidation), whereas it had no effect when administered before morphine
      during the conditioning phase (acquisition) or before testing for place
      preference in the absence of morphine (expression). It is concluded that the PKA
      II may play an active role in the consolidation of reward-related memory of
      morphine in CA1 region of the hippocampus.

PMID- 17174387
TI  - Pragmatic exercise-oriented prevention of falls among the elderly: a population
      based, randomized, controlled trial.
AB  - OBJECTIVES: To assess the effectiveness of an intervention planned and
      implemented by regional geriatric care teams in order to prevent falls in an
      elderly population. METHODS: The study was conducted among 555 (67%) home
      dwelling Finnish persons aged 85 years or older of a representative population
      sample (N=827) in 2000-2003. Altogether 486 subjects (88%) had a history of
      recurrent falls or at least one risk factor for disability in the activities of
      daily living or mobility and were randomly assigned to receive suggestions for a
      programme consisting of home exercise, walking exercise, group activities or self
      care exercise or alternatively routine care. Falls were monitored for a median of
      16 months during the intervention. RESULTS: The time to first four falls and all
      falls did not significantly differ in the targeted intervention group (N=217);
      compared to controls (N=220), hazard ratio 0.88 (95% CI 0.74 to 1.04) and 0.93
      (0.80-1.09), respectively. Among those able to move outdoors, the corresponding
      hazard ratios in the intervention group (N=168) compared to the controls (N=178)
      were 0.78 (0.64-0.94) and 0.88 (0.74-1.05). After the intervention period,
      impaired balance was less common in the intervention than in the control
      subjects; 64 (45%) and 89 (59%) (p<0.05). CONCLUSIONS: A pragmatic intervention
      was not effective in reducing the falling risk at the population level, but
      slowed down the reduction of balance performance. Among those able to move
      outdoors, the intervention was also effective in reducing the risk of first four
      falls.

PMID- 17174388
TI  - Effect of surface conditioning methods on the microtensile bond strength of resin
      composite to composite after aging conditions.
AB  - OBJECTIVES: This study evaluated the effect of two different surface conditioning
      methods on the repair bond strength of a bis-GMA-adduct/bis-EMA/TEGDMA based
      resin composite after three aging conditions. METHODS: Thirty-six composite resin
      blocks (Esthet X, Dentsply) were prepared (5 mm x 6 mm x 6 mm) and randomly
      assigned into three groups for aging process: (a) immersion in citric acid (pH
      3.0 at 37 degrees C, 1 week) (CA); (b) boiling in water for 8h (BW) and (c)
      thermocycling (x5000, 5-55 degrees C, dwell time: 30s) (TC). After aging, the
      blocks were assigned to one of the following surface conditioning methods: (1)
      silica coating (30 microm SiO(x)) (CoJet, 3M ESPE)+silane (ESPE-Sil) (CJ), (2)
      phosphoric acid+adhesive resin (Single Bond, 3M ESPE) (PA). Resin composite
      (Esthet.X) was bonded to the conditioned substrates incrementally and light
      polymerized. The experimental groups formed were as follows: Gr1:CA+PA;
      Gr2:CA+CJ; Gr3:BW+PA; Gr4: BW+CJ; Gr5:TC+PA; Gr6: TC+CJ. The specimens were
      sectioned in two axes (x and y) with a diamond disc under coolant irrigation in
      order to obtain non-trimmed bar specimens (sticks, 10 mm x 1 mm x 1 mm) with 1
      mm(2) of bonding area. The microtensile test was accomplished in a universal
      testing machine (crosshead speed: 0.5 mm min(-1)). RESULTS: The means and
      standard deviations of bond strength (MPa+/-S.D.) per group were as follows: Gr1:
      25.5+/-10.3; Gr2: 46.3+/-10.1; Gr3: 21.7+/-7.1; Gr4: 52.3+/-15.1; Gr5: 16.1+/
      5.1; Gr6, 49.6+/-13.5. The silica coated groups showed significantly higher mean
      bond values after all three aging conditions (p<0.0001) (two-way ANOVA and Tukey
      tests, alpha=0.05). The interaction effect revealed significant influence of TC
      aging on both silica coated and acid etched groups compared to the other aging
      methods (p<0.032). Citric acid was the least aggressive aging medium.
      SIGNIFICANCE: Chairside silica coating and silanization provided higher resin
      resin bond strength values compared to acid etching with phosphoric acid followed
      by adhesive resin applications. Thermocycling the composite substrates resulted
      in the lowest repair bond strength compared to citric acid challenge or boiling
      in water.

PMID- 17174389
TI  - Effect of different photoinitiator systems on conversion profiles of a model
      unfilled light-cured resin.
AB  - OBJECTIVE: The aim of this study was to compare the efficiency of different
      camphorquinone (CQ)/amine photo-initiating systems for the photopolymerization of
      a model dental resin based in Bis-GMA/TEGDMA. METHODS: The monomer conversion
      versus exposure time was measured in resins containing different types and
      concentrations of photoinitiators and subjected to different irradiation
      procedures. The conversion profiles during photopolymerization were investigated
      using near-infrared spectroscopy (NIR). CQ was used in combination with
      dimethylaminoethylmethacrylate (DMAEMA), ethyl-4-dimethylaminobenzoate (EDMAB), 4
      (N,N-dimethylamino)phenethyl alcohol (DMPOH), and N,N-3,5-tetramethylaniline
      (TMA) at different concentrations. RESULTS: From the conversion profiles, the
      approximate order of the accelerating ability of the respective amines were EDMAB
      approximately DMPOH>TMA>DMAEMA. The conversion profiles of all resins were
      sensitive to the illumination period. For a given exposure time, samples cured by
      sequential illumination resulted in lower conversion than samples cured by
      continuous irradiation. These results were attributed to a combination of both
      photo and thermal effects. NIR demonstrated to be a convenient method to follow
      the evolution of the monomer conversion during the photopolymerization of dental
      resins and, consequently, it is of great utility as a method for determining the
      relative efficacy of different photoinitiator. SIGNIFICANCE: The DMPOH/benzoyl
      peroxide redox system, has been recently proposed as a more biocompatible
      accelerator for the polymerization of acrylic resins. The results obtained in the
      present study reveal the potential usefulness of the DMPOH amine in light-cured
      dental composites.

PMID- 17174390
TI  - Functional diversity of nematode communities in the southwestern North Sea.
AB  - A range of biological traits of nematode species were combined to identify
      patterns in the functional composition of their assemblages collected at 19 soft
      bottom stations in the southwestern North Sea with the primary aim to determine
      which environmental variables control communities. We used 19 categories of five
      biological traits thought or known to represent an important ecological function.
      These were related to buccal morphology, tail shape, body size, body shape and
      life history strategy. Data on trait membership was provided by biological
      information on species and genera. A total of 79 different trait combinations
      were recorded. Results from correlation analyses revealed several significant
      relationships between traits. Some trait combinations were shared by different
      species and genera, and the ratio of realised versus total number of possible
      trait combinations of < 1 suggested that some trait combinations were not
      represented by the nematode fauna from this region. The functional composition of
      nematodes was strongly linked to median particle diameter and silt content of the
      sediment and water depth. The approach adopted and our attempts at defining and
      analysing functional attributes of nematode communities raised a number of
      conceptual and methodological issues which are discussed.

PMID- 17174391
TI  - The effect of cholecyst-derived extracellular matrix on the phenotypic behaviour
      of valvular endothelial and valvular interstitial cells.
AB  - Cholecyst-derived extracellular matrix (CEM) is a novel, proteinaceous
      biomaterial, derived from the porcine cholecyst, which may have potential
      applications as a scaffold in the area of heart valve tissue engineering. In this
      study the potential of CEM to support the proliferation of valvular endothelial
      cells (VECs) and valvular interstitial cells (VICs), while maintaining their
      phenotypic mRNA synthesis, protein expression and morphology was assessed by
      biochemical assays, electron microscopy, immunostaining and reverse-transcriptase
      polymerase chain reaction. VICs and VECs were isolated from the porcine aortic
      valve and techniques were developed for the isolation of CEM for cell culture.
      VECs and VICs cultured on CEM adhered and proliferated, maintaining their
      phenotypic morphology. VECs synthesised von Willebrand factor mRNA and
      endothelial nitric oxide synthase (eNOS) mRNA and expressed eNOS and VICs
      synthesised alpha-smooth muscle actin (alphaSMA) mRNA and expressed alphaSMA.
      Cellular area fraction of VICs expressing alphaSMA was 87.7+/-6.8% and cellular
      area fraction of VECs expressing eNOS was 93.8+/-9.3%. Findings of this study
      support the hypothesis that CEM is a potential biomaterial for tissue engineered
      heart valve scaffold design.

PMID- 17174392
TI  - Cell interaction with three-dimensional sharp-tip nanotopography.
AB  - Cells in their native microenvironment interact with three-dimensional (3D)
      nanofeatures. Despite many reports on the effects of substrate nanotopography on
      cells, the independent effect of 3D parameters has not been investigated. Recent
      advances in nanofabrication for precise control of nanostructure pattern,
      periodicity, shape, and height enabled this systematic study of cell interactions
      with 3D nanotopographies. Two distinct nanopatterns (posts and grates) with
      varying three-dimensionalities (50-600 nm in nanostructure height) were created,
      while maintaining the pattern periodicity (230 nm in pitch) and tip shape (needle
      or blade-like sharp tips). Human foreskin fibroblasts exhibited significantly
      smaller cell size and lower proliferation on needle-like nanoposts, and enhanced
      elongation with alignment on blade-like nanogrates. These phenomena became more
      pronounced as the nanotopographical three-dimensionality (structural height)
      increased. The nanopost and nanograte architectures provided the distinct contact
      guidance for both filopodia extension and the formation of adhesion molecules
      complex, which was believed to lead to the unique cell behaviors observed.

PMID- 17174393
TI  - The peripheral-type benzodiazepine receptor is involved in control of Ca2+
      induced permeability transition pore opening in rat brain mitochondria.
AB  - The peripheral-type benzodiazepine receptor (PBR) is an 18 kDa mitochondrial
      membrane protein with still elusive function in cell death. Here, we studied
      whether PBR is involved in Ca2+-induced permeability transition pore (PTP)
      opening in isolated rat brain mitochondria (RBM). PTP opening is important in
      mitochondrial events leading to programmed cell death. Immunoblots revealed a
      single 18 kDa anti-PBR antibody-immunoreactive band in purified RBM. Adenine
      nucleotide transporter, a key PTP component, was found in the PBR
      immunoprecipitate. In isolated intact RBM, addition of a specific anti-PBR
      antibody [H. Li, Z. Yao, B. Degenhardt, G. Teper, V. Papadopoulos, Cholesterol
      binding at the cholesterol recognition/interaction amino acid consensus (CRAC) of
      the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by
      an HIV TAT-CRAC peptide, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 1267-1272]
      delayed Ca2+-induced dissipation of membrane potential (psi(m)) and diminished
      cyclosporine A-sensitive Ca2+ efflux, which are both indicative for the
      suppression of PTP opening. Moreover, anti-PBR antibody caused partial retention
      of Ca2+ in the mitochondrial matrix in spite of psi(m) dissipation, and reduced
      activation of respiratory rate at Ca2+-induced PTP opening. A release of pro
      apoptotic factors, AIF and cytochrome c, from RBM was shown at threshold Ca2+
      load. Anti-PBR antibody blocked the release of AIF but did not affect the
      cytochrome c release. Addition of ATP was able to initiate PTP closing,
      associated with psi(m) restoration and Ca2+ re-accumulation. At the same time
      mitochondrial protein phosphorylation (incorporation of 32P from [gamma-32P]ATP)
      occurred and anti-PBR antibody was able to inhibit phosphorylation of these
      proteins. The endogenous PBR ligand, protoporphyrin IX, facilitated PTP opening
      and phosphorylation of the mitochondrial proteins, thus, inducing effects
      opposite to anti-PBR antibody. This study provides evidence for PBR involvement
      in PTP opening, controlling the Ca2+-induced Ca2+ efflux, and AIF release from
      mitochondria, important stages of initiation of programmed cell death.

PMID- 17174394
TI  - A bioavailability model predicting the toxicity of nickel to rainbow trout
      (Oncorhynchus mykiss) and fathead minnow (Pimephales promelas) in synthetic and
      natural waters.
AB  - The effects of Ca, Mg and pH on the toxicity of Ni to juvenile rainbow trout
      (Oncorhynchus mykiss) were examined during 17-26-day exposures to Ni in 15
      synthetic test solutions. Higher chemical activities of Ca2+, Mg2+ and H+ reduced
      Ni toxicity, as demonstrated by increased 17-day median lethal concentrations
      expressed as Ni2+ activity (17-d LC50(Ni2+)). A non-linear increase of the 17-d
      LC50(Ni2+) with increasing H+ suggested that the effect of pH could not be
      appropriately described by single-site competition between Ni(2+) and H+ for
      sensitive sites on the fish gill. Instead, a linear increase of pNi2+ (=-log 17-d
      LC50(Ni2+)) with increasing pH was observed with a slope of 0.32. This slope was
      used as the basis for modelling the effect of pH. The effects of Ca and Mg were
      modelled according to single-site competition with logK(CaBL)=logK(MgBL)=3.6,
      both assumed to be independent of pH. The effect of pH was superimposed on this
      competition effect and was also assumed to be independent of Ca and Mg
      concentrations. The model was able to predict 17-d LC50s (expressed as dissolved
      Ni) in most synthetic test waters within a factor 2 deviation from observed
      toxicity. The model's predictive capacity was also evaluated using results of
      similar laboratory toxicity tests with juvenile rainbow trout in Ni-spiked
      European natural surface waters. For most of these waters, predicted 17-d LC50s
      did not deviate more than a factor 2 from observed toxicity. The same model,
      calibrated to account for sensitivity differences between species, life stages
      and/or exposure durations, was able to accurately predict 96-h LC50s for larval
      and juvenile fathead minnow (Pimephales promelas) and juvenile rainbow trout,
      based on data taken from literature. Although the developed model seems very
      promising, the uncertainty around the role of alkalinity and the exact mechanisms
      by which Ca, Mg and pH modify Ni toxicity need to be further explored.

PMID- 17174395
TI  - Determining sediment quality for regulatory proposes using fish chronic
      bioassays.
AB  - Sediment quality assessments for regulatory purposes (i.e. dredged material
      disposal) are characterized by linking chemical and acute ecotoxicological data.
      The design of chronic bioassays that incorporate more sensible endpoints than
      acute tests is discussed to address sediment quality for environmental quality
      assessment and regulatory proposes. The chronic tests use juveniles of commercial
      species of fish Sparus aurata and Solea senegalensis, to assess sediment toxicity
      in samples collected along different littoral areas in the North and the South of
      Spain. The organisms were exposed during 60 days and sublethal endpoints were
      selected including biomarkers of exposure to metals (metallothioneins - MTs) and
      to organic contaminants (ethoxyresorufin-O-deethylase activity - EROD activity)
      and biomarkers of effect (histopathology in different tissues, gill and liver). A
      Multivariate Analysis Approach was conducted in order to associate these
      biological responses with sediment metal concentration from the ports and with
      chemical residues in biological tissues exposed to sediments under laboratory
      conditions.

PMID- 17174396
TI  - Liquid versus solid phase bioassays for dredged material toxicity assessment.
AB  - Since 1994 the results of the analyses of key chemical compounds (trace metals,
      polychlorinated biphenyls and polycyclic aromatic hydrocarbons) and the
      comparison with the corresponding sediment quality guidelines (SQGs) are used in
      decision-making for dredged material management in Spain. Nonetheless in the last
      decades a tiered testing approach is promoted for assessing the physical and
      chemical characteristics of dredged sediments and their potential biological
      effects in the environment. Bioassays have been used for sediment toxicity
      assessment in Spain but few or no experiences are reported on harbour sediments.
      We studied the incidence of toxicity in the 7 d bioassay using rotifers
      (Brachionus plicatilis) and the 48 h bioassay using sea urchin (Paracentrotus
      lividus) embryos over a series of experiments employing 22 different elutriates.
      The relative performance of this exposure phase was not comparable to data on the
      10-d acute toxicity test using the burrowing amphipod Corophium volutator and the
      polychaete Arenicola marina, carried out on the whole sediments. These results
      evidence the importance of the exposure route and the test selected in decision
      making, as the toxicity registered for the undiluted elutriates was largely due
      to the different solubility of sediment-bound contaminants. This work and other
      studies indicate that for many sediments, a complete battery of test is
      recommended together with physico-chemical analyses to decide whether dredged
      sediments are suitable for open water disposal or not.

PMID- 17174397
TI  - Nuclear receptors and susceptibility to chemical exposure in aquatic organisms.
AB  - Nuclear receptors (NRs) constitute a superfamily of transcriptional factors that
      participate in homeostasis and development through the binding of endogenous
      compounds. Despite this constitutive activity, some xenobiotics can also bind to
      NRs and disturb some signaling pathways, giving rise to the concept that NR
      activity can be modulated by antagonists or competitive agonists. Some NRs, such
      as the Pregnane X receptor (PXR), Peroxisome Proliferator Activated Receptors
      (PPARs) and Constitutive Androstane Receptor (CAR) have received particular
      attention because after binding to xenobiotics, they activate the expression of
      genes involved in Phases I, II and III of biotransformation pathways. Another
      important protein involved in the signaling of toxic compounds is the aromatic
      hydrocarbon receptor (AhR), a member of the basic helix loop-helix (bHLH) PER
      ARNT-SIM (PAS) family of nuclear transcription factors. AhR modulates an
      important panel of cognate genes and is remarkably prone to protein-protein
      interactions interfering with transcription factors and NRs. Several observations
      have been made associating the exposure to chemicals with adverse effects on
      reproduction of aquatic organisms, termed endocrine disrupting compounds (EDC).
      NRs are believed to play an essential role in the adverse effects elicited by EDC
      and some mechanisms are addressed in this review.

PMID- 17174398
TI  - Expression and secretion of immunoglobulin alpha heavy chain with diverse VDJ
      recombinations by human epithelial cancer cells.
AB  - Generally, only B lymphocytes express immunoglobulin. Recently, we found the
      expression of Ig alpha heavy chain in human epithelial cancer cells unexpectedly.
      We first detected Ig VDJ-Calpha and Ialpha-Calpha transcripts in multiple cancer
      cell lines. Further, the configuration of the Ig heavy chain genomic locus was
      analyzed in human cancer cells. We found that cancer cells have the recombination
      VDJ region, but bear Ig Salpha region in germline configuration, which is
      different from Ig expression pattern in B cells. And human epithelial cancers
      possess the essential effectors including RAG-1 and RAG-2, but not activation
      induced cytidine deaminase (AID) protein. These provide further proofs for Ig
      alpha expression. In addition, we found that human cancer cells not only express
      the protein of Ig alpha chain, but also secrete the protein in secretory IgA
      (SIgA) pattern. Importantly, diverse CDR3 recombinations were found in human
      cancer cells of different epithelial origin. Since IgA is the key immunoglobulin
      which contributes to local immunity of mucous membrane, the aberrant expression
      of Ig alpha heavy chain might increase our further comprehension to development
      and immunity of cancers.

PMID- 17174399
TI  - Surgeon volumes and selected patient outcomes in cataract surgery: a population
      based analysis.
AB  - OBJECTIVE: To study the association of annual surgeon volume of cataract
      procedures with the risk of postoperative adverse events. DESIGN: We used
      population-based administrative health records to conduct a retrospective cohort
      study from 2001 through 2003. PARTICIPANTS: The number of surgeons who performed
      more than 50 cataract surgeries annually ranged from 231 to 243 over the 3 years.
      There were 284 797 cataract surgeries in patients older than 20 years performed
      at 70 hospitals or eye surgery centers in the province of Ontario, Canada.
      METHODS: We calculated cataract surgery volume for each surgeon and tested for
      the presence of a volume-outcome association. We used generalized estimating
      equations to account for the effect of clustering of patients according to
      individual surgeons and to adjust estimates for the potential confounding effects
      of patient age and gender. MAIN OUTCOME MEASURES: We used a composite outcome of
      postoperative adverse events from cataract surgery that included billing claims
      for vitrectomy, vitreous aspiration or injection of medication, vitreous air or
      fluid exchange, and dislocated lens extraction performed by any ophthalmologist
      between 1 and 14 days after cataract surgery. These procedures are surrogate
      markers for the outcomes of retinal detachment, lost lens or lens fragment, and
      suspected endophthalmitis. RESULTS: In each year, fewer than 1 in 200 patients
      experienced an adverse event (range, 0.33%-0.41%). Surgeons performing 50 to 250
      cataract surgeries per year had an adverse event rate of 0.8%. Surgeons
      performing 251 to 500 cataract surgeries per year had an adverse event rate of
      0.4% and an adjusted odds ratio of postoperative adverse events of 0.52 (95%
      confidence interval [CI], 0.39-0.69) compared with surgeons performing 50 to 250
      procedures per year. Surgeons performing 501 to 1000 cataract surgeries per year
      had an adverse event rate of 0.2% and an adjusted odds ratio of 0.31 (95% CI,
      0.22-0.43), and surgeons performing more than 1000 cataract surgeries per year
      had an adverse event rate of 0.1% and an adjusted odds ratio of 0.14 (95% CI,
      0.09-0.23). CONCLUSIONS: Selected adverse event rates for surgeons performing
      more than 50 cataract surgeries per year are low. There is a volume-outcomes
      relationship for cataract surgery, and this relationship persists even for very
      high-volume surgeons.

PMID- 17174400
TI  - Role of antiretroviral treatment in prolonging QTc interval in HIV-positive
      patients.
AB  - OBJECTIVES: The aims of our study were to assess the prevalence of QTc
      prolongation in a group of HIV-infected individuals and to evaluate the
      associated risk factors. METHODS: All the 650 HIV-infected patients followed up
      at our outpatient clinic underwent ECG recording. A "nested" case-control study
      was performed using as cases 64 HIV-infected patients with QTc > 0.44 s and as
      controls (1:4) 256 HIV-positive subjects matched by gender and age with QTc
      interval < or = 0.44 s. RESULTS: A prolonged QTc interval was found in 9.8% of
      HIV-positive individuals (64/650). In the nested case-control study, an increased
      risk of having a prolonged QTc interval was observed among patients taking
      nelfinavir, efavirenz, methadone, cotrimoxazole or an excessive amount of
      alcohol. When a zidovudine (AZT)-containing backbone was associated with
      nelfinavir-based or efavirenz-based antiretroviral therapy, the risk of having a
      prolonged QTc interval was about three times higher than in patients taking
      nelfinavir or efavirenz without AZT. CONCLUSIONS: Several drugs administered to
      HIV-infected patients may cause a QTc interval prolongation increasing the risk
      of serious arrhythmias. An ECG follow-up for the assessment of QTc seems to be
      advisable for HIV-infected patients receiving drugs with a QTc prolonging
      potential.

PMID- 17174401
TI  - Community-acquired pneumonia due to Bordetella holmesii in a patient with
      frequently relapsing nephrotic syndrome.
AB  - Bordetella holmesii is a rare cause of human infection, mainly in the
      immunocompromised host, and is associated with bacteremia, respiratory tract
      infection and endocarditis. Herein, we describe a patient with severe relapse of
      nephrotic syndrome associated with bacteremic B. holmesii pneumonia.

PMID- 17174402
TI  - High-field diffusion tensor imaging of mouse brain in vivo using single-shot
      STEAM MRI.
AB  - Information about the microstructural organization of cerebral white matter that
      is accessible by magnetic resonance diffusion tensor imaging (DTI) gains
      increasing importance for studies of animal brain. Particular challenges occur
      for in vivo conditions as well as at high magnetic fields. Here, we have employed
      a diffusion-weighted (DW) single-shot STEAM MRI sequence for DTI of mouse brain
      in vivo at 7 T. The approach exploits the increased longitudinal magnetization
      and prolonged T1 relaxation times of water protons at higher magnetic field
      strengths without suffering from susceptibility-induced artifacts. When compared
      to studies at 2.35 T, half Fourier DW STEAM MRI at 7 T yielded a substantial gain
      in signal-to-noise ratio (SNR) that could be invested either in a reduction of
      the measurement time or an increase of the spatial resolution. Thus, for a
      measurement time of 3h, DTI with a voxel size of 117 microm x 117 microm x 720
      microm not only resulted in high-quality maps of the fractional anisotropy and
      main diffusion direction (MDD), but also allowed for fiber tracking of major
      mouse brain structures in vivo.

PMID- 17174403
TI  - Dynamic programming algorithms for comparing multineuronal spike trains via cost
      based metrics and alignments.
AB  - Cost-based metrics formalize notions of distance, or dissimilarity, between two
      spike trains, and are applicable to single- and multineuronal responses. As such,
      these metrics have been used to characterize neural variability and neural
      coding. By examining the structure of an efficient algorithm [Aronov D, 2003.
      Fast algorithm for the metric-space analysis of simultaneous responses of
      multiple single neurons. J Neurosci Methods 124(2), 175-79] implementing a metric
      for multineuronal responses, we determine criteria for its generalization, and
      identify additional efficiencies that are applicable when related dissimilarity
      measures are computed in parallel. The generalized algorithm provides the means
      to test a wide range of coding hypotheses.

PMID- 17174404
TI  - Improvement in mood and ideation associated with increase in right caudate
      volume.
AB  - BACKGROUND: The basal ganglia, particularly caudate, are hypothesized to play a
      role in affective and obsessive-compulsive disorders. The depressive syndrome is
      a feature of untreated Cushing's disease. The objective of this study was to test
      the hypothesis that after treatment of Cushing's disease reduces elevated
      cortisol, improvement in mood and related ideations are associated with increase
      in caudate volume. METHODS: In this longitudinal, interventional study of 23
      patients with Cushing's disease, 24-hour urinary free cortisol, structural
      magnetic resonance imaging and behavioral measures were obtained prior to
      treatment and approximately one year after pituitary microadenomectomy. Five SCL
      90-R subscales measuring change in mood, related ideations and physical symptoms
      were utilized. RESULTS: Partial correlations (adjusted for age and time since
      surgery) showed change in caudate, but not hippocampal, volume was significantly
      associated with change in behavioral SCL-90-R subscales, indicating selectivity
      for structure. Right but not left caudate showed associations, suggesting
      selectivity for lateralization. Right caudate volume increase was significantly
      associated with decreases in Depression, Anxiety, Obsessive-Compulsive, and
      Paranoid scores, but not with Somatization (physical symptoms), indicating
      specificity for behavioral but not physical variables. LIMITATIONS: A limitation
      is that relatively low-resolution scans were utilized. Although most likely not
      diminishing the significant findings, less sensitive methodology could lead to an
      increased probability of a type 2 error. CONCLUSIONS: These findings support the
      concept that caudate, and likely right caudate, participates in human brain
      circuitry regulating mood.

PMID- 17174405
TI  - Prefrontal cortical functional abnormality in major depressive disorder: a
      stereotactic meta-analysis.
AB  - OBJECTIVE: First, the objective was to test the hypothesis that prefrontal
      cortical regions most often reported to be maximally abnormal in studies of major
      depressive disorder, correspond to those regions reported maximally active when
      healthy subjects engage in diverse emotional tasks. Second, the objective was to
      determine whether such regions are reported typically to be either over or under
      active. METHOD: Medline and Embase were used to search for neuroimaging studies
      of major depressive disorder from 1990 to 2005. Forty-two original studies using
      voxel based techniques were included, and compared with data from our previous
      meta-analysis on healthy subjects which included one hundred and eighty-one
      original studies [Steele, J.D., Lawrie, S.M., 2004b. Segregation of cognitive and
      emotional function in the prefrontal cortex: a stereotactic meta-analysis.
      Neuroimage 21, 868-875]. RESULTS: The medial prefrontal cortex is the region
      reported maximally abnormal most often when healthy subjects experience emotion.
      The region is centred on Broadmans Area (BA) 32 but extends into BA 25. Two
      further clusters of reported loci were identified in the lateral prefrontal
      cortex: one in the lateral orbitofrontal region reported active when healthy
      subjects experience emotion (BA 47); the other centred on a dorsolateral region
      (BA 46 and 9) associated with cognitive tasks. No reporting bias for overactivity
      or underactivity was identified. LIMITATIONS: This study pooled data from diverse
      studies deliberately. There were insufficient numbers of original studies to
      support sub-group analyses. CONCLUSIONS: Despite the variability of reports in
      the literature, activity reported to be abnormal in depressive disorder is
      particularly localised to those brain regions that represent the substrate for
      normal emotional experience in healthy subjects.

PMID- 17174406
TI  - Patients' perceptions of information received about medication prescribed for
      bipolar disorder: implications for informed choice.
AB  - BACKGROUND: Previous research suggests that patients are dissatisfied with
      information provided about medication prescribed for mental illness, but has not
      identified which aspects of information provision are unsatisfactory. METHODS:
      223 members of the Manic Depression Fellowship (MDF) completed the Satisfaction
      with Information about Medicines Scale (SIMS), a validated measure of patients'
      satisfaction with various aspects of information provision. RESULTS: Patients
      reported highest dissatisfaction with information about potential problems
      associated with medication; over 60% of participants reported dissatisfaction
      with information about the risks of side effects and whether the medication would
      affect their sex lives. Participants were significantly less satisfied with
      information about potential problems associated with their medication than people
      prescribed medication for HIV in a previously reported study (p<.01). Those
      reporting low adherence to medication had significantly lower satisfaction with
      information scores than those reporting high adherence (p<.05). LIMITATIONS: The
      sample could be prone to selection bias; participants were members of an
      organisation for people affected by bipolar disorder, whilst the comparator group
      was a NHS HIV clinic sample. Furthermore, the objective amount and type of
      information provided was not assessed, therefore the cause of patients'
      dissatisfaction is not known. CONCLUSIONS: Perceived satisfaction with
      information is low, particularly in relation to possible drug side-effects.
      Health practitioners need to elicit individuals' information requirements and
      tailor information to meet their needs, in order to facilitate informed choice
      and adherence to treatment. Moreover, they need to provide information in a
      manner appropriate for a patient's cognitive functioning at different illness
      phases.

PMID- 17174407
TI  - Effects of chronic stress on the immune response to oral human serum albumin
      conjugated starch microparticles in rats.
AB  - Uptake of antigens and bacteria over the follicle-associated epithelium (FAE) is
      increased after chronic psychological stress. We investigated whether stress
      affects the immune response to particle-conjugated antigens taken up via the FAE.
      Rats were submitted to two 10-day periods of water avoidance stress and orally
      immunized during these periods. Stressed immunized rats displayed altered cell
      populations and a Th1-skewed immune response within the lymphoid follicles,
      together with enhanced delayed-type hypersensitivity. We conclude that chronic
      stress affects the cell-mediated immune response after oral immunization, which
      may have implications for the understanding of allergic and autoimmune diseases
      and development of oral vaccines.

PMID- 17174408
TI  - The mastoid as a functional rate-limiter of middle ear pressure change.
AB  - INTRODUCTION: The physiological function of the mastoid air cell system (MACS)
      with respect to middle ear (ME) pressure-regulation remains controversial because
      predictive mathematical models and experimental data to formulate and test
      hypotheses are lacking. OBJECTIVE: A mathematical description of MACS volume
      effects on the rate of ME pressure change is presented; the agreement between
      published data and model prediction is examined for consistency with the
      hypothesis that the MACS acts as a functional rate-limiter of ME pressure change,
      and an explanation for the relationship between MACS volume and otitis media is
      discussed. METHODS: The mathematical description shows that the value of a
      single, free parameter, termed the "MACS buffering efficiency" (M) determines if
      MACS volume affects the rate of ME pressure change caused by diffusive gas
      exchange. The MACS serves no rate-limiting function for M=0, acts as a gas sink
      for M>1 and acts as a gas reserve (rate-limiter) for M<1. RESULTS: Fitting the
      model equation to published adult human data yielded an estimate for M of 0.2.
      This implies that larger MACS volumes are associated with lesser rates of change
      in ME pressure caused by diffusive gas exchange and lesser required frequencies
      of effective Eustachian tube openings to maintain near ambient ME pressures.
      CONCLUSION: If well-controlled studies confirm M<1 for children and adults,
      larger MACS volumes will increase the time required to develop sufficient ME
      underpressures to cause otitis media by hydrops ex vacuo during transient or
      prolonged periods of Eustachian tube dysfunction.

PMID- 17174409
TI  - Successful application of FTA Classic Card technology and use of bacteriophage
      phi29 DNA polymerase for large-scale field sampling and cloning of complete maize
      streak virus genomes.
AB  - Leaf samples from 155 maize streak virus (MSV)-infected maize plants were
      collected from 155 farmers' fields in 23 districts in Uganda in May/June 2005 by
      leaf-pressing infected samples onto FTA Classic Cards. Viral DNA was successfully
      extracted from cards stored at room temperature for 9 months. The diversity of
      127 MSV isolates was analysed by PCR-generated RFLPs. Six representative isolates
      having different RFLP patterns and causing either severe, moderate or mild
      disease symptoms, were chosen for amplification from FTA cards by bacteriophage
      phi29 DNA polymerase using the TempliPhi system. Full-length genomes were
      inserted into a cloning vector using a unique restriction enzyme site, and
      sequenced. The 1.3-kb PCR product amplified directly from FTA-eluted DNA and used
      for RFLP analysis was also cloned and sequenced. Comparison of cloned whole
      genome sequences with those of the original PCR products indicated that the
      correct virus genome had been cloned and that no errors were introduced by the
      phi29 polymerase. This is the first successful large-scale application of FTA
      card technology to the field, and illustrates the ease with which large numbers
      of infected samples can be collected and stored for downstream molecular
      applications such as diversity analysis and cloning of potentially new virus
      genomes.

PMID- 17174411
TI  - Detection and quantitation of Solenopsis invicta virus in fire ants by real-time
      PCR.
AB  - A quantitative real-time PCR (QPCR) method was developed to detect and quantify
      the amount of Solenopsis invicta virus (SINV) infecting individual ants of S.
      invicta. The two-step method utilized a gene-specific oligonucleotide primer
      targeting the SINV RNA-dependent RNA polymerase (RdRp) for cDNA synthesis.
      Dithiothreitol used in the cDNA synthesis step was found to significantly
      decrease the detection sensitivity for SINV RdRp and was therefore omitted. SINV
      RdRp cDNA was then quantified by QPCR using SYBR Green dye and a standard curve
      generated from SINV RdRp plasmid clones. A standard curve was successfully
      constructed from clones of the SINV RdRp region. A strong linear relationship
      [r2=0.998; y=(-3.63+/-0.37)x+(39.19+/-1.33)] between C(T) and starting SINV RdRp
      copy number was observed within a dynamic range of 5-5 x 10(6) copies. SINV RdRp
      copy number was determined with the optimized QPCR method in individual S.
      invicta ants taken from an infected field colony. Worker ants exhibited the
      highest RdRp copy number (2.1 x 10(9) copies/worker ant) and pupae exhibited the
      lowest (4.2 x 10(2) copies/pupa). Mean RdRp copy number was lowest in early
      larvae and pupae. Overall, SINV RdRp copy number increased through larval
      development, sharply declined during pupation, then sharply increased in adults.

PMID- 17174410
TI  - Preparation and evaluation of a recombinant Rift Valley fever virus N protein for
      the detection of IgG and IgM antibodies in humans and animals by indirect ELISA.
AB  - This paper describes the cloning, sequencing and bacterial expression of the N
      protein of the Rift Valley fever virus (RVFV) ZIM688/78 isolate and its
      evaluation in indirect ELISAs (I-ELISA) for the detection of IgM and IgG
      antibodies in human and sheep sera. Sera used for the evaluation were from 106
      laboratory workers immunised with an inactivated RVF vaccine, 16 RVF patients,
      168 serial bleeds from 8 sheep experimentally infected with wild type RVFV and
      210 serial bleeds from 10 sheep vaccinated with the live attenuated Smithburn
      RVFV strain. All human and animal sera that tested positive in the virus
      neutralisation test were also positive in the IgG I-ELISA. There was a high
      correlation (R2=0.8571) between virus neutralising titres and IgG I-ELISA
      readings in human vaccinees. In experimentally infected sheep IgG antibodies were
      detected from day 4 to 5 post-infection onwards and IgM antibodies from day 3 to
      4. The IgG I-ELISA was more sensitive than virus neutralisation and
      haemagglutination-inhibition tests in detecting the early immune response in
      experimentally infected sheep. The I-ELISAs demonstrated that the IgG and IgM
      response to the Smithburn vaccine strain was slower and the levels of antibodies
      induced markedly lower than to wild type RVFV infection.

PMID- 17174412
TI  - Chicks discriminate human gaze with their right hemisphere.
AB  - Domestic chicks were tested for eye use while feeding on the floor in the
      presence of a dummy mask which could either look at the location where the chicks
      were feeding or in the opposite direction. Animals completely naive of visual
      experience of human eyes and gaze showed a more intense fear response when
      directly looked at (as shown by higher latency to approach the food) and a
      preferential use of the left eye (mainly feeding structures in their right
      hemisphere) to monitor the dummy mask. This response, seemingly predisposed,
      could be reversed in chicks with experience of human eyes and gaze directed
      toward them, which showed higher latency to approach the food and preferential
      left eye use when the dummy mask looked away from them. The results are discussed
      in relation to evidence for a right hemisphere involvement in fear responses and
      detection of predators in the vertebrate brain.

PMID- 17174413
TI  - Effects of genetic background and environmental novelty on wheel running as a
      rewarding behaviour in mice.
AB  - Recent studies suggest running wheel activity to be naturally rewarding and
      reinforcing; considering the shared neuro-behavioural characteristics with drug
      induced reward situations, wheel running behaviour gains interest as a tool to
      study mechanisms underlying reward-sensitivity. Previously, we showed that wheel
      running has the potential to disrupt the daily organization of home cage
      behaviour in female C57BL/6 [de Visser L, van den Bos R, Spruijt BM. Automated
      home cage observations as a tool to measure the effects of wheel running on cage
      floor locomotion. Behav Brain Res 2005;160:382-8]. In the present study, we
      investigated the effects of novelty-induced stress on wheel running and its
      impact on home cage behaviour in male C57BL/6 and DBA/2 mice. Our aim was to
      determine whether wheel running may be used as a tool to study both genetic and
      environmentally induced differences in sensitivity to rewarding behaviour in
      mice. One group of male mice was placed in an automated home cage observation
      system for 2 weeks with a wheel integrated in the cage. A second group of mice
      was allowed to habituate to this cage for 1 week before a running wheel was
      introduced. Results showed a pronounced sensitising effect of novelty on the
      level of wheel running in C57Bl/6 mice but not in DBA mice. Overall levels of
      wheel running were higher in DBA/2 mice. Furthermore, wheel running affected
      circadian rhythmicity in DBA/2 mice but not in C57BL/6 mice. From these findings
      we tentatively suggest that wheel running behaviour could serve as a tool to
      study the interaction between genetic and environmental factors in sensitivity to
      rewarding behaviour in mice. As it is displayed spontaneously and easy to
      monitor, wheel running may be well suitable to be included in high-throughput
      phenotyping assays.

PMID- 17174415
TI  - Effects of a pyrethroid pesticide on endocrine responses to female odours and
      reproductive behaviour in male parr of brown trout (Salmo trutta L.).
AB  - Reproductive behaviour of brown trout (Salmo trutta L.) from an anadromous stock
      was studied in a large stream water aquarium. Four adult males and two ovulated
      females were placed in the aquarium together with eight mature male parr. Four of
      the parr were exposed during the previous 4 days to two concentrations (0.1 or
      1.0 microgl(-1)) of the pyrethroid pesticide cypermethrin (a disrupter of
      olfactory receptor function) and four of the parr to the solvent ethanol. The
      behaviour of all fish was followed for 24h and then blood and milt was collected.
      Exposure to the higher concentration of cypermethrin disturbed the reproductive
      behaviour of the parr. They displayed fewer courting events, spent less time near
      the nesting females and had lower volumes of strippable milt. They also had
      significantly lower amounts of 11-ketotestosterone (11-KT) in the blood plasma
      than the control group. The higher cypermethrin group also had significantly
      lower levels of all these variables than the lower cypermethrin group, apart from
      strippable milt that showed no significant differences between two groups. No
      significant differences in non-reproductive behaviours were observed between any
      of the groups. In the control fish, there were significant positive correlations
      between (a) the number of courting events and the amount of time spent near the
      female, (b) blood plasma levels of 17alpha,20beta-dihydroxy-4-pregnen-3-one
      (17,20beta-P) and time spent near the female and (c) plasma levels of 17,20beta-P
      and the number of courting events. Further, in control fish, higher plasma levels
      of 17,20beta-P were observed in parr interacting with a female compared to those
      with no female contacts. A priming experiment confirmed a previous study that
      cypermethrin damages olfactory reception. Parr exposed to cypermethrin had
      significantly lower blood plasma levels of 17,20beta-P and 11-KT than control
      males after exposure to ovarian fluid and urine (known to contain reproductive
      priming pheromones). When ethanol-exposed males were exposed to ovarian fluid and
      urine they had significantly higher plasma levels of 17,20beta-P compared to
      those exposed to water only.

PMID- 17174416
TI  - Involvement of endothelial NO in the dilator effect of VIP on rat isolated
      pulmonary artery.
AB  - The endothelium and its interaction with smooth muscle play a central role in the
      local control of the pulmonary vasculature, and endothelial dysfunction is
      thought to contribute to pulmonary hypertension and chronic obstructive pulmonary
      disease. Vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide,
      relaxes the rat pulmonary artery, but there is controversy as to whether or not
      this action of VIP depends on the endothelium. The aim of this study, therefore,
      was to investigate the role of the endothelium and nitric oxide (NO), the major
      endothelium-derived relaxing factor, in the dilator action of VIP on the rat
      isolated pulmonary artery. Pulmonary artery preparations pre-contracted by the
      alpha(1)-adrenoceptor agonist L-phenylephrine were relaxed by VIP (0.003-1
      microM) and acetylcholine (0.003-10 microM) in a concentration-dependent manner.
      Mechanical removal of the endothelium reduced the maximal response to VIP by
      about 50% and practically abolished the response to acetylcholine. Inhibition of
      NO synthesis by N(omega)-nitro-L-arginine methyl ester (0.5 mM) had a similar
      effect, abolishing the vasorelaxation caused by acetylcholine and attenuating the
      vasorelaxation caused by VIP by about 50%. From these data it is concluded that
      the relaxant action of VIP on the rat isolated pulmonary artery depends in part
      on the presence of the endothelium and that this part is mediated by endothelial
      NO.

PMID- 17174414
TI  - Courtship and copulation in the adult male green anole: effects of season,
      hormone and female contact on reproductive behavior and morphology.
AB  - Interactions among reproductive season, testosterone (T) and female presence were
      investigated on the structure and function of forebrain and neuromuscular systems
      controlling courtship and copulation in the green anole lizard. Under breeding
      (BS) or non-breeding (NBS) environmental conditions, male green anoles were
      implanted with either T or blank capsules and exposed to one of three female
      stimulus conditions: physical, visual or no female contact. T and at least visual
      exposure to females increased courtship displays (extension of a throat fan, or
      dewlap), and these effects were greater during the BS than NBS. T also
      facilitated copulation, and did so to a greater extent in the BS. The hormone
      increased soma size in the preoptic area (POA) and amygdala (AMY), and in the AMY
      the effects were greater in the BS than NBS. Cross-sectional areas of copulatory
      organs and associated muscle fibers were enhanced by T, and more so in the BS
      than NBS. However, no effects on morphology of dewlap motoneurons or muscles or
      copulatory motoneurons were detected. Thus, (1) changes in behavior and neural
      and/or muscular morphology are not always parallel and (2) differences in
      responsiveness to T exist across seasons and among tissues.

PMID- 17174417
TI  - Role of oral sildenafil in severe pulmonary arterial hypertension: clinical
      efficacy and dose response relationship.
AB  - BACKGROUND: Sildenafil (phosphodiesterase type 5 inhibitor) has been shown to be
      effective in pulmonary arterial hypertension (PAH). We evaluated the efficacy and
      safety of oral sildenafil in patients of severe PAH with special emphasis on dose
      response relationship, time of onset of clinical response and its effects on
      different haemodynamic parameters. METHODS: Forty-four patients of severe PAH of
      either idiopathic pulmonary arterial hypertension [23 (51.7%)] or Eisenmenger
      syndrome [21 (48.3%)] were studied. All patients underwent six-minute walk test
      (SMWT) and echocardiography, while some also underwent cardiac catheterization.
      Sildenafil was started after a test dose and was gradually increased up to a
      target dose of 300 mg/day. Patients were followed-up 2 weekly for 10 weeks and
      monthly thereafter for functional class assessment and SMWT. Echocardiography and
      cardiac catheterization were repeated after at least 1 month of achieving maximal
      sildenafil dose (target dose or maximally tolerated dose). Drug safety and
      tolerability were assessed by monitoring patients for adverse effects including
      fundus examination. RESULTS: Mean follow-up duration was 18.7+/-8.8 months (range
      7-30 months). Mean maximum dose achieved was 276.1+/-62.2 mg/day (range 75-300
      mg/day). A significant improvement in NYHA class (2.54+/-0.5 vs. 1.31+/-0.4,
      p=0.0001) and in SMWT distance (247.4+/-74.7 vs. 366.3+/-93.8 m, p=0.0001) was
      noted. All patients reported "feeling better" within 2 weeks of starting 12.5 mg
      thrice a day sildenafil. Marked improvement was noticed at 150 mg/day dose. Some
      minor additional benefit was noticed with further increase in the dose up to 225
      mg/day. No further benefit was noted in improvement of NYHA class and SMWT
      distance by further increasing the dose of sildenafil. Haemoptysis as well as
      chest pain, if present, were also improved. On follow-up cardiac catheterization,
      a significant reduction in mean pulmonary arterial pressure (from 67.0+/-10.2 to
      56.9+/-9.5 mm Hg, p=0.001), PVRI (from 19.5+/-7.0 to 11.1+/-6.9 WU m2, p=0.0001)
      and PVR/SVR ratio (0.6+/-0.3 vs. 0.4+/-0.2, p=0.013) with increase in cardiac
      index (2.9+/-1.1 l/min vs. 3.7+/-1.1 l/min, p=0.008) was noted. Systemic as well
      as pulmonary arterial oxygen saturations also improved significantly. Sildenafil
      was generally well tolerated, except for rhinorrhoea in 2, bodyache in 1 and
      headache in 1 patient. No visual symptom or change in fundus examination was
      noted. CONCLUSIONS: Oral sildenafil improves functional capacity, haemodynamic
      parameters and is safe in patients with severe PAH. Benefits start as early as 2
      weeks. The effects are dose related. A target dose of 150 mg/day appears to be
      optimal. Being very effective, widely available, relatively inexpensive, and very
      easy to use and very well tolerated without any major side effect, sildenafil may
      qualify as a first line medication for these patients.

PMID- 17174418
TI  - Effects of chronic sildenafil in patients with Eisenmenger syndrome versus
      idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: To test the hypothesis that chronic sildenafil treatment has similar
      functional and hemodynamic effects in patients with severe pulmonary arterial
      hypertension due to Eisenmenger syndrome as those due to idiopathic pulmonary
      arterial hypertension without intracardiac shunts. METHODS: A prospective open
      label study was carried out to compare the effects of sildenafil on the pulmonary
      hemodynamics between two groups of patients with severe pulmonary hypertension
      and similar baseline functional capacity--Eisenmenger syndrome (ES group) (n=7)
      versus idiopathic pulmonary arterial hypertension (IPAH group) (n=6). RESULTS:
      After 6 months of sildenafil, there was a significant improvement in the
      functional capacity, the arterial saturation and the pulmonary hemodynamics in
      the ES group, as shown by significant reduction in the systolic and mean
      pulmonary artery pressures and the pulmonary vascular resistance. CONCLUSION:
      Sildenafil increases pulmonary blood flow and improves cyanosis in patients with
      Eisenmenger syndrome. Efficacy of sildenafil as treatment for idiopathic
      pulmonary arterial hypertension may be extended to patients with Eisenmenger
      syndrome.

PMID- 17174419
TI  - Prognostic value of renal function in patients with cardiac resynchronization
      therapy.
AB  - BACKGROUND: Renal insufficiency is prevalent in patients with heart failure and
      indicates poor prognosis. We examine (i) the relationship between left
      ventricular (LV) reverse remodeling (RR) and renal function and (ii) the
      prognostic value of renal function in patients receiving cardiac
      resynchronization therapy (CRT). METHODS: The relationship between LV-RR, defined
      as a 10% reduction in LV end-systolic volume, and renal function was examined in
      85 consecutive patients receiving CRT. Echocardiographic assessment and renal
      function tests were performed before and 3 months after CRT. All-cause mortality
      and the composite of mortality or heart failure hospitalization between those
      with preserved or deteriorated renal function at 3 months were assessed by Kaplan
      Meier analysis. RESULTS: There was a slight improvement in glomerular filtration
      rate (GFR) in those with LV-RR (n=44; 51.7+/-20.4 vs. 54.2+/-19.1 ml/min/1.73 m2;
      p=0.024) while a significant deterioration (n=41; 61.9+/-17 vs. 48.8+/-13.0
      ml/min/1.73 m2; p<0.001) was observed in those without LV-RR. The change (Delta)
      in GFR was significantly correlated with DeltaLV end-systolic/diastolic volumes
      and DeltaLV ejection fraction. After follow up of 856.4+/-576.8 days, patients
      with preserved renal function had significant lower all-cause mortality (log rank
      chi2=4.82, p=0.029) and the composite endpoints (log rank chi2=5.04, p=0.025).
      CONCLUSION: Preservation of renal function was observed in patients with systolic
      heart failure and renal insufficiency responding to CRT and provided prognostic
      information. A rapid decline in renal function after CRT was associated with
      worse clinical outcomes.

PMID- 17174420
TI  - Prevalance of anemia and its association with cardio-renal syndrome.
AB  - BACKGROUND: Anemia is common in cardio-renal syndrome and may contribute to
      increase mortality. OBJECTIVE: To examine the prevalence of anemia and its
      relationship with cardio-renal syndrome, and to evaluate the risk factors for
      death. METHODS: Retrospective study with all patients admitted with congestive
      heart failure (CHF). The parameters as age, gender, hemoglobin (Hb), estimated
      glomerular filtration rate (eGFR), New York Heart Association (NYHA) functional
      class, ejection fraction (EF%), hospital stay, hypertension, diabetes, smoking
      and CHF etiology were analyzed. Anemia was defined as Hb<12 g/dL, systolic
      dysfunction EF<55% and renal failure was stratified according to K-DOQI
      classification. Statistical analysis was done by the programs EpiInfo and SPSS
      for windows. RESULTS: A total of 174 patients were studied. The average age was
      63+/-16 years, 65.5% were males, and 18 of them (11%) were non-survivors. Anemia
      was observed in 45% of patients, and 82% presented some degree of renal failure.
      The majority of patients (87%) were classified as NYHA functional class III or
      IV. The average ejection fraction was 43.9+/-16.6%, and there was no difference
      between survivors and non-survivors (p>0.05). Mortality was not significantly
      higher among patients with anemia (12.4%) when comparing to those without anemia
      (8.3%, p=0.31). There was a progressive decrease in the level of hemoglobin as
      renal function decreased (p<0.05). Increased serum creatinine was a significant
      risk factor for death (OR=1.59, 95% CI=1.074-2.363, p=0.021), and increased EF%
      was a protection factor against development of death (OR=0.904, 95% CI=0.845
      0.973, p=0.007). CONCLUSIONS: The prevalence of anemia is high among patients
      with cardio-renal syndrome but was not associated with increased mortality.
      Increased serum creatinine and low EF% were variables associated with death.

PMID- 17174421
TI  - Impaired nitrate-mediated dilatation could reflect nitrate tolerance in patients
      with coronary artery disease.
AB  - AIM: To investigate whether nitrate-mediated dilatation (NMD) of the brachial
      artery could be impaired by the use of nitrates and reflect nitrate tolerance in
      coronary artery disease (CAD) patients. METHODS: A total of 243 patients (mean
      age 61+/-12 years, 146 male) were recruited before coronary angiography. Gensini
      score was calculated to assess the severity of CAD. Flow-mediated dilatation
      (FMD) and NMD of the brachial artery were measured. RESULTS: NMD progressively
      decreased from subjects without CAD (control group, n=71) to non-nitrate users
      (n=64) and nitrate users (n=108) with CAD (16.2+/-6.01% versus 13.4+/-5.57%
      versus 9.57+/-4.52%, P<0.001 for all). Multiple linear regression analysis showed
      that age, FMD, diameter of the brachial artery, hypertension, and nitrate use
      were independent determinants of NMD. In subgroup analysis of patients with high
      Gensini score (>10), nitrate users (n=56, 9.00+/-4.00%) had a significant lower
      NMD than non-users (n=28, 12.4+/-5.45%, P<0.001), but no difference in other
      parameters including age, prevalence of hypertension, FMD, Gensini score and use
      of other medications. CONCLUSIONS: The use of nitrates independently impaired NMD
      in CAD patients. An impaired NMD could be a comprehensive index of nitrate
      tolerance in patients with CAD.

PMID- 17174422
TI  - Chinese authors' names should include their names in Chinese.

PMID- 17174424
TI  - Rationality and drug use: an experimental approach.
AB  - In rational addiction theory, higher discount rates encourage drug use. We test
      this hypothesis in the general framework of rationality and behaviour under risk.
      We do so using an experimental design with real monetary incentives. The
      decisions of 34 drug addicts are compared with those of a control group. The
      decisions of drug users (DU) are not any less consistent with standard theories
      of behaviour over time and under risk. Further, there is no difference in the
      estimated discount rate between drug users and the control group, but the former
      do appear to be more risk-seeking.

PMID- 17174423
TI  - Serial NT-proBNP monitoring and outcomes in outpatients with decompensation of
      heart failure.
AB  - BACKGROUND: NT-proBNP is useful for heart failure (HF) diagnosis and prognosis.
      We examined the value of serial NT-proBNP monitoring to predict outcomes in
      decompensated HF patients attending a structured HF clinic. METHODS: Patients
      with decompensation of established optimally treated HF, not requiring emergency
      hospital admission, were enrolled in the study. Patients received intensive
      follow-up weekly during 4 weeks and at 3 months in specialist HF clinics. Serial
      NT-proBNP concentrations were measured at each visit. Primary endpoint was
      cardiovascular death and hospital admission for HF at 3 months. RESULTS: Fifty
      nine patients were enrolled (60+/-14 years, LVEF 27+/-9%) and 39% had a primary
      endpoint during follow-up. Baseline NT-proBNP concentration (in ng/L) was 7050+/
      6620, and did not differ significantly in patients with and without events
      (p=0.22). Patients without events showed marked NT-proBNP reduction at week-1
      (30% reduction), week-2 (36% reduction), week-3 (34% reduction) and week-4 (37%
      reduction). By contrast, patients with events showed no significant NT-proBNP
      reduction during follow-up. Using a general linear model, the relative NT-proBNP
      reductions (%) at weeks 1-4 were predictors of adverse events (p=0.004, p<0.001,
      p=0.001 and p=0.03, respectively). In a stepwise multiple Cox regression
      analysis, NT-proBNP relative reduction (in %) at week 2 was a strong predictor of
      no events during follow-up (OR 0.79, 95% CI 0.70-0.88, p<0.001). CONCLUSIONS:
      Serial NT-proBNP monitoring in decompensated HF patients seen in a structured in
      hospital HF clinic predicts cardiovascular events during follow-up. NT-proBNP may
      be useful in an outpatient basis to identify patients at high risk needing more
      aggressive therapy.

PMID- 17174425
TI  - Molecular farming on the rise--GMO regulators still walking a tightrope.
AB  - Recent increases in EU commercial and academic activities in molecular farming,
      and the proximity to market-stage of the first plant-made pharmaceuticals,
      represent a call to action for EU regulators. Drawing on the North American
      debate on molecular farming, it will be argued that both the rationale and the
      risks of molecular farming will differ significantly from those of first
      generation GM crops. Based on these differences, the suitability of the existing
      regulatory frameworks, which were developed in response to the arrival of earlier
      products, is discussed, and specific options for adapting the already complex EU
      regulatory system to cater for molecular farming are examined.

PMID- 17174426
TI  - CARD15 variants in patients with sporadic Parkinson's disease.
AB  - Recent reports have proven the importance of genetic factors and inflammation in
      the pathogenesis of sporadic Parkinson's disease (PD). In the current study, the
      frequency of CARD15/NOD2 gene variants (R702W, G908R, L1007fs), previously
      associated with Crohn's disease--a common inflammatory bowel disease, have been
      examined in a group of 308 sporadic PD patients and 220 healthy controls.
      Significantly higher frequency of total CARD15 variant alleles in PD patients
      (13.0%) compared to the controls (8.0%, p<0.02) was observed. 24.0% of PD
      patients carried at least one CARD15 variant allele compared to 15.5% of healthy
      controls (p<0.02, OR=1.73). The results of the study suggest, that the
      polymorphism in CARD15/NOD2 gene may be a risk factor for sporadic PD
      development, and support the concept of inflammatory pathogenesis of PD.

PMID- 17174427
TI  - Treatment of green table olive solutions with ozone. Effect on their polyphenol
      content and on Lactobacillus pentosus and Saccharomyces cerevisiae growth.
AB  - Disposition of green table olives alkaline solutions (GTOS) remains a major task
      for the industry with serious environmental implications. The presence of high
      concentrations of polyphenols in olives also presents a problem for direct
      brining and successful fermentation step. In this study we evaluated the effect
      of ozone treated GTOS on the growth of Saccharomyces cerevisiae and Lactobacillus
      pentosus. GTOS were treated with ozone for 24 and 72 h. The treatment caused a
      rapid destruction of polyphenols but did not affect sugar concentration. S.
      cerevisiae grew in the original and treated liquids, although its maximum
      specific growth rate (mu(m)) and its population size increased as the ozone
      treatment was longer. L. pentosus was completely inhibited in the original and 24
      h ozone treated GTOS, but grew in 72 h treated solutions. Co-culture with S.
      cerevisiae improved L. pentosus performance. Diluting the original GTOS with
      distilled water in several ratios, and adding MRS medium (50 g/L) to ensure
      nutrient availability, showed that a complete inhibition on L. pentosus did never
      occur; however, its mu(m) progressively increased, and the lag phase period
      (lambda) decreased linearly, with increasing dilutions levels. The inhibition
      effect was lower in 24 h ozone treated GTOS and disappeared completely in those
      treated for 72 h. Furthermore, treatment of GTOS with ozone always improved
      microbial growth.

PMID- 17174428
TI  - Computer aided boar semen motility analysis for cereulide detection in different
      food matrices.
AB  - Computer Aided Semen Analysis (CASA) study of the boar semen motility has been
      demonstrated to be an appropriate assay for detection of cereulide (Bacillus
      cereus emetic toxin). Application of the boar semen bio-assay to detect cereulide
      directly in foods requires investigation of potential interference of food
      components, preservatives and other microbial and chemical food contaminants with
      the bio-assay. Current study provides evidence that none of included
      Staphylococcus aureus enterotoxins A, B, C and D nor B. cereus Hemolysin BL (HBL)
      and non-hemolytic enterotoxin (NHE) and three mycotoxins (Sterigmatocystin,
      Fumonisin B1 and Patulin) exhibited a toxic impact on semen progressive motility.
      Aflatoxin M1, M3 and zearalenone impaired semen motility only at concentrations
      (0.004 mg ml(-1), 0.1 mg ml(-1) and 10 mg ml(-1), respectively) much higher than
      those found in foods and those permitted by legislation, in comparison to
      cereulide which induces motility cease at concentrations lower than 20 ng ml(-1).
      Ten commonly used preservatives, namely potassium sorbate, sodium benzoate, (DL)
      malic acid, citric acid, (L+) tartaric acid, acetic acid, (DL) lactic acid, (L+)
      ascorbic acid, sodium chloride and sucrose induced no cease in spermatozoa
      motility even at preservative concentrations higher than permitted by
      legislation. Dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and acrylamide
      had no acute effect on spermatozoa motility at concentrations of 500 and 10,000
      mg ml(-1), respectively. Robustness of computer aided boar semen motility
      analysis, tested with 14 different foods inoculated with cereulide producing B.
      cereus, showed distinct cereulide production in seven samples (although B. cereus
      growth to counts higher than 8 log CFU g(-1) was noted in 11 samples), in amounts
      close to those reported in foodborne outbreaks. Test evaluation in 33 samples
      suspected to hold cereulide showed actual cereulide presence in ten samples and
      no interference of food matrix with the assay.

PMID- 17174429
TI  - Enzymatic activities of lactic acid bacteria isolated from Cornetto di Matera
      sourdoughs.
AB  - Forty-one strains of lactic acid bacteria (LAB) isolated from Cornetto di Matera
      sourdoughs were screened for their enzymatic activities, to elucidate their
      possible roles during the fermentation process. Urease, peptidase, phytase,
      phosphatase and beta-glucosidase activities were measured spectrophotometrically
      using synthetic substrates. Proteolytic activities were examined in model doughs,
      using neutral and acidified sterile doughs as controls. All strains had low
      urease, glutamyl aminopeptidase and iminopeptidase activities, whereas
      differences within species were observed for the other enzymatic activities.
      Leuconostoc mesenteroides and Lactobacillus curvatus strains generally showed
      high aminopeptidase, X-prolyl dipeptidyl aminopeptidase, beta-glucosidase and
      phytase activities, while the enzymatic activities of Lactobacillus plantarum,
      Lactobacillus pentosus and Weissella cibaria varied between strains. In order to
      classify the strains on the basis of similar enzymatic profiles, a hierarchical
      cluster analysis was carried out. Several strains of L. plantarum, L. curvatus
      and Leuc. mesenteroides showed an interesting combination of proteolytic,
      peptidase, beta-glucosidase and phytase activities, suggesting their possible
      usefulness as a mixed starter culture in bread-making processes.

PMID- 17174430
TI  - Development and application of Multiple-Locus Variable number of tandem repeat
      Analysis (MLVA) to subtype a collection of Listeria monocytogenes.
AB  - In this study we report the development and application of a Multiple-Locus
      Variable number of tandem repeat Analysis (MLVA) strategy for subtyping Listeria
      monocytogenes. Genome profiles of a collection of forty-five food-borne L.
      monocytogenes isolates were compared using MLVA. These isolates were obtained as
      part of an active surveillance programme of foods in the south-east region of
      Ireland. MLVA successfully discriminated amongst the isolates. The method was
      easy to perform, relatively fast and could be deployed in any molecular
      laboratory with basic laboratory equipment. This approach is a valuable tool,
      which has the capability to provide comparable results when compared with other
      more established typing methods, including pulsed-field gel electrophoresis
      (PFGE).

PMID- 17174431
TI  - Isoflavone phytoestrogen degradation in fermented soymilk with selected beta
      glucosidase producing L. acidophilus strains during storage at different
      temperatures.
AB  - Soymilk fermented with 3 selected Lactobacillus acidophilus strains were stored
      at various temperatures (-80 degrees C, 4 degrees C, 25 degrees C and 37 degrees
      C) for 8 weeks and the concentration of isoflavones determined weekly using RP
      HPLC. The decreasing concentration of isoflavones in soymilk during storage due
      to degradation was found to fit the first order kinetics model. Isoflavone
      aglycones as well as isoflavone glucosides largely appeared to be stable during
      storage (P<0.01). Interestingly, the aglycone forms showed much smaller
      degradation as compared to glucoside forms at all the storage temperatures
      studied. Of the isoflavone aglycones, daidzein was found to be the most stable
      followed by genistein, while glycitein was least stable. Isoflavone aglycones
      such as glycitein, daidzein and genistein showed smaller degradation constants in
      fermented soymilk at lower storage temperatures (-80 degrees C and 4 degrees C)
      and higher degradation constants at higher storage temperatures (25 degrees C and
      37 degrees C) with each strain. In contrast, glucosides glycitin and daidzin
      showed higher degradation at lower storage temperatures (-80 degrees C and 4
      degrees C) and lower degradation at higher storage temperatures (25 degrees C and
      37 degrees C). Storage temperature was therefore found to be very important in
      regulating the rate of degradation soy isoflavones in fermented soymilk.

PMID- 17174432
TI  - Factors associated with Listeria monocytogenes contamination of cold-smoked pork
      products produced in Latvia and Lithuania.
AB  - A total of 312 samples of sliced, vacuum packaged, cold-smoked pork from 15 meat
      processing plants in Latvia and Lithuania, obtained over a 15-month period from
      2003 until 2004, were analyzed for the presence of Listeria monocytogenes at the
      end of their shelf-life. Overall, 120 samples (38%) tested positive for L.
      monocytogenes. Despite the long storing period, the levels of L. monocytogenes in
      cold-smoked pork products were low. Manufacturing processes were studied at seven
      meat processing plants. A new approach with a logistic multivariable regression
      model was applied to identify the main factors associated with L. monocytogenes
      contamination during the manufacturing of cold-smoked pork products. Brining by
      injection was a significant factor (odds ratio 10.66; P<0.05) for contamination
      of product with L. monocytogenes. Moreover, long cold-smoking times (> or = 12 h)
      had a significant predictive value (odds ratio 24.38; P<0.014) for a sample to
      test positive for L. monocytogenes. Pulsed-field gel electrophoresis results
      indicated that various sources of L. monocytogenes contamination existed over
      periods of time in several meat processing plants. In two meat processing plants,
      persistent L. monocytogenes strains belonging to serotypes 1/2a and 1/2c were
      found.

PMID- 17174433
TI  - Isolation and phylogenetic analysis of H1N1 swine influenza virus isolated in
      Korea.
AB  - A swine influenza H1N1 virus was isolated from a pig during a severe outbreak of
      respiratory disease in Korea. All genes of the H1N1 isolate, including
      hemagglutinin (HA), neuraminidase (NA), matrix (M), nucleoprotein (NP), non
      structural (NS), PA, PB1 and PB2, were of swine origin. Also, all these genes
      showed a close phylogenic relationship with those of H1N1 viruses previously
      isolated from pigs in the United States. These results suggest that North
      American swine influenza virus has actually been transmitted to pigs in Korea.

PMID- 17174434
TI  - [Evaluation of the Cheneau brace in adolescent idiopathic scoliosis].
AB  - OBJECTIVE: We aimed to evaluate the Cheneau brace in the orthopedic treatment of
      adolescent idiopathic scoliosis to better determine the indications under which
      it could be prescribed. MATERIALS AND METHODS: This was a retrospective study
      including 63 patients treated by Cheneau brace for adolescent idiopathic
      scoliosis between 1997 and 2006. The Cobb angles of the curves in the frontal and
      sagittal planes as well as rotations and rib hump were measured at the beginning
      of treatment, with the brace, at the end of treatment and 2 years after
      discontinuing the brace. A variation of+/-10 degrees in angle was selected to
      judge the results. RESULTS: At the end of the treatment, 25.4% of the curves were
      improved and 60.3% stabilized, with 14.3% aggravated; 5 patients (7.9%) required
      surgery. At 2 years, the reduction in angle was 1.8 degrees, on average. The best
      results were obtained for the lumbar and dorsolumbar curves. A significant
      improvement was noted for the dorsal curves; the major double curves are not as
      accessible to the treatment. For curves whose initial angle was less than 30
      degrees , an initial reduction of higher than 50% with the brace presented the
      best improvement at the end of the follow-up. We note a significant reduction of
      the rib hump but not accompanied by a reduction of rotation. Finally, we note a
      deleterious effect in the sagittal curves, with a slight flatness of the spinal
      profile. CONCLUSION: The continuous wearing of the Cheneau brace can stabilize
      the evolution of adolescent idiopathic scoliosis, apart from the forms with major
      double curves, which are not as accessible to the treatment. However, the
      improvement comes at the price of a slight flatness of the curves of the spine in
      the sagittal plane. The loss of the correction after discontinuing the brace is
      minor. We emphasize, therefore, the necessity to monitor the sagittal aspect of
      the spine as well as the possibility of early treatment, strict surveillance and
      prolonged follow-up.

PMID- 17174435
TI  - Measles supplemental immunization activities improve measles vaccine coverage and
      equity: Evidence from Kenya, 2002.
AB  - OBJECTIVES: To compare the measles vaccine coverage achieved through the routine
      vaccination program with that achieved during the 2002 supplemental immunization
      activity (SIA) at the national and provincial level, the percentage of previously
      unvaccinated children (zero-dose children) reached during the SIA, and the equity
      of measles vaccine coverage among children aged 9-23 months in Kenya. METHODS:
      Using data from a post-SIA coverage survey conducted in Kenya, we compute routine
      and SIA measles vaccine coverage and the percent of zero-dose children vaccinated
      during the SIA at the national and provincial level. Nationwide and for each
      province, we use the concentration index (CI) to measure equity of measles
      vaccine coverage. RESULTS: The SIA improved both coverage and equity, achieving
      significantly higher coverage in all provinces with routine measles vaccination
      coverage less than 80%, reached a large percentage of zero-dose children in these
      provinces, and reached more children belonging to the poorest households.
      CONCLUSION: Overall, by improving both measles vaccine coverage and equity in
      Kenya, the 2002 SIA reduced the gap in immunity between rich and poor households.
      Measles SIAs provide an ideal platform for delivering other life-saving child
      health interventions.

PMID- 17174436
TI  - A retrospective analysis of malignant pleural mesothelioma patients treated
      either with chemotherapy or best supportive care between 1990 and 2005 A single
      institution experience.
AB  - The aim of this study was to investigate the efficacy and safety profile of
      chemotherapy (CT) compared to best supportive care (BSC) in patients with
      histopathologically confirmed diffuse malignant pleural mesothelioma (DMPM). A
      total of 161 patients between 1990 and 2004 treated either with CT (109 patients)
      or BSC (52 patients) depending on patients choice were evaluated in this
      analyses. Chemotherapy protocols included a combination of cisplatin, mitomycin C
      and recombinant interferon alpha 2a (CM-In), or cisplatin, mitomycin C and
      ifosfamide (CMI), or cisplatin and gemcitabine (CG). We found a significant
      difference in the median survivals of the patients with CT compared to BSC, 11.3
      months versus 8.0. Objective response rate was 28/109 (25.7%) with 3.7% of
      complete response rate. Stable disease rate was 39/109 (35.8%). There was a
      significant difference between median survivals of patients with objective
      response (17 months) and median survivals of patients with progressive diseases
      (6 months) and also with stable diseases (16 months). There was a significant
      difference between the stable disease and the progressive disease. Stages 3 and 4
      patients of epithelial cell type having received chemotherapy live longer than
      those not having received chemotherapy (12 months versus 4). There was no
      significant difference between the survivals of the different chemotherapy
      regimens. The toxicity with CT regimens were mild and well-tolerated. We conclude
      that CT prolongs survival compared to BSC in patients with DMPM. Survivals of
      patients with objective response prolong considerably with CT compared BSC. We
      observed that stages 3 and 4 patients with epithelial cell type got benefit from
      CT. Especially, of epithelial cell type stages 1 and 2 should receive multimodal
      treatment.

PMID- 17174437
TI  - Aryl hydrocarbon receptor gene polymorphisms affect lung cancer risk.
AB  - To evaluate the role of genetic polymorphisms of AhR related to the carcinogen
      metabolism and cell proliferation, genotypes of three AhR polymorphisms
      Ex1+185A>G, IVS7+33T>G and Ex10+501G>A were determined in 616 lung cancer cases
      and 616 lung cancer-free controls. When the effect of each AhR allele on lung
      cancer risk was evaluated, any AhR genotype did not show the association with
      lung cancer risk. However, when haplotypes were composed of three AhR SNP sites,
      non-smokers with GGG haplotype (adjusted OR=1.7, 95% CI, 1.06-2.71) and smokers
      without GGG haplotype (adjusted OR=2.5, 95% CI, 1.64-3.74) showed significantly
      increased risk of lung cancer compared to non-smokers without GGG haplotype.
      Moreover, smokers with GGG haplotype showed the highest risk (adjusted OR=3.2,
      95% CI, 2.10-4.74). Particularly, the synergistic effect between AhR haplotype
      and smoking was more apparent in squamous cell carcinoma (adjusted OR=6.1, 95%
      CI, 2.53-14.68). This result suggests that haplotypes of AhR gene play an
      important role in the development of lung cancer and there is a synergistic
      interaction between AhR gene and smoking for lung cancer risk.

PMID- 17174439
TI  - Evaluation of air permeability in layered unsaturated materials.
AB  - Field estimation of air permeability is important in the design and operation of
      soil-vapor extraction systems. Previous models have examined airflow in
      homogenous soils, incorporating leakage through a low-permeability cap either as
      a correction to the airflow equation or as a boundary condition. The dual leakage
      model solution developed here improves upon the previous efforts by adding a
      leaky lower boundary condition, allowing for the examination of airflow in
      heterogeneous layered soils. The dual leakage model is applied to the evaluation
      of pump tests at a pilot soil-vapor extraction system at the Savannah River Site
      in South Carolina. A thick, low-permeability, stiff clay layer divides the
      stratigraphy at the site into two units for evaluation. A modified version of the
      previous model, using the water table as the impermeable lower boundary, is used
      to evaluate the permeability of the low-permeability stiff clay layer (3.2 x 10(
      10) cm(2)) and permeable sand (7.2 x 10(-7) cm(2)) beneath it. The stiff clay
      permeability estimate is used in the evaluation of the shallow unit. Permeability
      estimates of the shallow sand (3.8 x 10(-7) cm(2)) and kaolin cap (1.5 x 10(
      9)cm(2)) were obtained with the dual leakage model. The shallow unit was
      evaluated using the previous model for comparison. The effects of anisotropy were
      investigated with a series of model simulations based on the shallow unit
      solution. The anisotropy sensitivity analysis suggests that increased anisotropy
      ratio or decreased axial permeability has a significant impact on the velocity
      profile at the lower boundary, especially at high values of the anisotropy ratio.
      This result may increase estimates of SVE removal rates for contaminants located
      at the interface of the lower boundary, typical of chlorinated solvent
      contamination.

PMID- 17174438
TI  - Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in
      Caucasians and African Americans: a population-based study.
AB  - Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction
      of enzymatic activity towards several substrates, including those found in
      tobacco smoke. To investigate the potential role these polymorphisms have as
      modulators of early-onset lung cancer risk, a population-based case-control study
      involving early-onset lung cancer cases was performed. Biological samples were
      available for 383 individuals diagnosed prior to 50 years of age identified from
      the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER)
      program and 449 age, race and sex-matched controls ascertained through random
      digit dialing. Genotype frequencies varied significantly by race for CYP1A1
      Ile(462)Val and CYP1B1 Leu(432)Val genotypes, so all analyses were stratified by
      race. No association was seen between lung cancer risk and polymorphisms in
      CYP1A1 Msp1 or CYP1B1 Leu(432)Val for Caucasians or African Americans, after
      adjusting for age at diagnosis, sex, pack years of smoking and family history of
      lung cancer. In Caucasians, those with the IIe/Val genotype at CYP1A1 Ile(462)Val
      locus were at decreased risk of having lung cancer compared to those with the
      lle/lle genotype, after adjusting for age at diagnosis, sex, pack years of
      smoking and family history of cancer (OR=0.41 95% Cl 0.19-0.90). These results
      were not replicated among the African American population, nor were they modified
      by amount of smoking.

PMID- 17174440
TI  - Prevalence of non-tuberculous mycobacteria in a hospital environment.
AB  - In recent years, non-tuberculous mycobacteria (NTM) have emerged as an important
      cause of opportunistic nosocomial infections but there is little known about the
      isolation and identification of NTM in Korea. The aim of this study was to assess
      the prevalence of NTM in the hospital environment and identify the species. A
      total of 150 samples were collected from different parts of the hospital. NTM
      were isolated and identified by restriction fragment length polymorphism analysis
      of the gene encoding rpoB and partial sequencing analysis of hsp65 and rpoB. In
      this study, 60 strains of NTM were isolated from 50 of the 150 samples. Half of
      the tap water samples (50 of 100) were positive for mycobacteria. An estimated
      73.3% of the isolates were saprophytic, 21.7% were potentially pathogenic and 5%
      were unidentified. The presence of NTM in hospital tap water is not uncommon.
      Such water isolates might cause true nosocomial infection in immunocompromised
      patients, in addition to the risk of false-positive culture results.

PMID- 17174441
TI  - Phlebotomy tourniquets and MRSA.

PMID- 17174442
TI  - Relationship between hand rub consumption and nosocomial infection rates in
      intensive care units.

PMID- 17174443
TI  - Interactions between Mycobacterium xenopi, amoeba and human cells.
AB  - Outbreaks due to Mycobacterium xenopi have been linked with contaminated water.
      M. xenopi has been shown to interact with the biofilm formed in water
      distribution systems and to be hosted by free-living Acanthamoeba. The present
      study investigated the interaction between M. xenopi and A. polyphaga amoeba, and
      between M. xenopi and human fibroblast HEL cells. Examination using the light
      microscopy together with electronic and confocal microscopy demonstrated that M.
      xenopi was located within the amoeba and in HEL cells. The Light Cycler
      measurement of the M. xenopi:A. polyphaga DNA ratio and the M. xenopi:HEL cell
      DNA ratio demonstrated intra-amoebal and intracellular growth of M. xenopi with
      doubling-times of five-days and 10 days, respectively. Intra-amoebal M. xenopi
      survived protozoan encystment and germination. These data demonstrate that M.
      xenopi is a facultative intra-amoebal and intracellular pathogen. Testing intra
      amoebal M. xenopi might be necessary to properly evaluate decontamination
      procedures for hospital water supply systems in order to achieve eradication.

PMID- 17174444
TI  - A statistical method for estimating the proportion of cases resulting from cross
      transmission of multi-resistant pathogens in an intensive care unit.
AB  - Multi-resistant bacteria are an increasing challenge for infection control in
      hospitals and the proportion of patients newly colonized with multi-resistant
      bacteria during their hospital stay can be used to assess the effectiveness of
      infection control measures. Current laboratory methods for estimating this
      require expensive additional tests. We propose an alternative statistical method
      to estimate the proportion of cases resulting from transmission in a hospital
      from the distribution of time intervals between subsequent cases. A prerequisite
      for the application of this method is the existence of records from regular
      screening of the patients during their hospital stay, usually performed in
      intensive care units (ICUs). We describe the method and present an example of its
      application using records of two multi-resistant pathogens collected in an ICU
      over a three-year period. The estimated proportion of cases resulting from
      transmission was 0.73 (95% CI: 0.56-0.90) for meticillin-resistant Staphylococcus
      aureus and 0.45 (95% CI 0.15-0.75) for imipenem-resistant Pseudomonas aeruginosa.
      The method proposed here can be used for retrospective evaluation of clinical
      records in order to evaluate the effectiveness of infection control measures in
      low endemicity settings.

PMID- 17174445
TI  - Needlestick injuries and other occupational exposures to body fluids amongst
      employees and medical students of a German university: incidence and follow-up.
AB  - The aim of this study was to obtain data concerning the incidence, reporting and
      follow-up of occupational exposure to blood or other body fluids (OEB). A
      questionnaire was distributed to employees and medical students (N=787) and
      official reports of OEB during the year 2003 (N=203) and their consequent follow
      up (N=100) were evaluated. The percentages of needlestick injuries were 29.5% for
      students and 22.5% for employees. Incidence rates per 1000 employee days were
      0.61 for needlestick injuries or sharp object injuries and 0.27 for mucocutaneous
      exposure to body fluids. The mean rate of underreporting was approximately 45%.
      Contrary to expectations, only 4.3% of nurses and 3.9% of doctors officially
      reported an OEB in 2003. The number of persons who did not attend for a
      serological test increased during the follow-up period. Considering all
      documented test results, 35 out of 100 affected persons were lost to follow-up
      due to default of appearance. As a consequence, the employer should provide
      safety devices and enforce didactical interventions with practical training and
      incident reporting. Periodical occupational health medicals, including
      serological testing, should be mandatory for all employees, including medical
      students and student nurses. To increase compliance after OEB, a short follow-up
      period using improved laboratory tests requires further discussion.

PMID- 17174446
TI  - Physician handwashing: what do parents want?
AB  - Transmission of micro-organisms from the hands of healthcare workers to patients
      is a major cause of healthcare-acquired infections. In 2002, the US Centers for
      Disease Control and Prevention (CDC) published guidelines for healthcare workers
      that included the recommendation for alcohol-based hand rub for hand hygiene
      during patient visits. In this prospective study we surveyed parental and
      healthcare workers' preferences for the hand hygiene practices of emergency
      physicians. The study comprised 99 parents of ill or injured children presenting
      to our emergency department and 100 healthcare providers (64 nurses, 29
      physicians and seven nurse practitioners) within the department. There was a
      clear and similar preference by parents and healthcare workers for hand hygiene
      using soap and water over alcohol cleansing rubs. Furthermore, both groups
      preferred hand hygiene before and after the examination and wanted to observe the
      physician perform this procedure. In conclusion, families and healthcare worker
      preferences for hand hygiene are not in keeping with recommendations published by
      the CDC. Educational interventions are needed to disseminate the CDC's guidelines
      and to promote compliance with evidence-based recommendations for hand hygiene.

PMID- 17174447
TI  - The CleanYourHandsCampaign: critiquing policy and evidence base.
AB  - Handwashing is considered to be the most effective way of reducing cross
      infection. Rates of healthcare-associated infection and the incidence of
      meticillin-resistant Staphylococcus aureus are higher in the UK than in many
      other European countries. The government has responded by introducing the
      'CleanYourHandsCampaign' throughout England and Wales, based on the success of
      the approach employed in Geneva. Alcohol hand rub is placed at every bedside in
      acute hospitals, ward housekeepers should replenish supplies and feedback on
      compliance is provided to health workers. Posters and other promotional materials
      are used to remind health workers and visitors to use the hand rub. Patients are
      encouraged to ask health workers if they have cleaned their hands before contact.
      In this paper we argue that the evidence base underpinning the
      CleanYourHandsCampaign is incomplete. Alcohol hand rub is acknowledged as a
      useful adjunct to hand hygiene but it is not effective in all circumstances.
      There is some evidence to support the use of feedback on performance to encourage
      compliance but no evidence that promotional materials such as posters or patient
      reminders are effective. The ethics of encouraging hospital patients to take
      responsibility for their own safety is questioned. Much of the success in Geneva
      must be attributed to the attention given to contextual factors within the
      organization that encouraged hand rub use, especially hospital-wide 'ownership'
      of the initiative by managers and senior health professionals. A customized
      intervention from another country that fails to consider local organizational
      factors likely to influence the implementation of the campaign is unlikely to be
      effective. It is concluded that although hand hygiene is of undoubted importance,
      undue emphasis should not be placed on it as a 'quick fix' to solve the
      unacceptably high rates of healthcare-associated infection in National Health
      Service hospitals.

PMID- 17174448
TI  - Evaluation of a new disinfection procedure for ultrasound probes using
      ultraviolet light.
AB  - Following 183 ultrasound examinations, a randomized trial was conducted to
      compare three procedures for disinfection of probes under routine conditions: dry
      wiping with a soft, dry, non-sterile paper towel, antiseptic wiping with a towel
      impregnated with disinfectant spray and dry wiping followed by a 10 min
      ultraviolet C (UVC) cycle in a disinfection chamber. After ultrasonography, swabs
      were taken from transducer heads before and after cleaning and streaked onto
      plates that were then cultured. The number of colonies per plate was counted and
      organisms identified. The median microbial reduction was 100% for UVC, 98.4% for
      antiseptic wiping and 87.5% for dry wiping (P<0.001). The percentage of negative
      specimens was 88% for UVC, 16% for antiseptic wiping and 4% for dry wiping
      (P<0.0001). Microbial flora was isolated from 12 probes (6.6%) before cleaning,
      whereas specimens obtained after cleaning contained no pathogens except in one
      case after antiseptic wiping. UVC disinfection of ultrasound probe may provide a
      useful method for reducing the bacterial load under routine conditions.

PMID- 17174449
TI  - Aging sensitizes mice to behavioral deficits induced by central HIV-1 gp120.
AB  - The number of older adults with HIV-1 disease is increasing but little is known
      about how age influences behavioral deficits associated with HIV-1 infection. The
      purpose of this study was to determine in a murine model if aging influenced
      sickness behavior following central injection of HIV-1 gp120. In initial studies,
      behavioral deficits induced by acute and repeated intracerebroventricular (ICV)
      injection of gp120 were greater in aged mice than in adults. Furthermore,
      repeated ICV injection of gp120 increased hippocampal levels of IL-1 beta and IL
      6 mRNA in aged mice but not in adults. To determine if IL-6, which is elevated in
      aged brain, affects expression of the gp120-binding target, CCR5, microglia (BV-2
      cell line) were incubated with increasing concentrations of IL-6. Cell surface
      expression of CCR5 was increased by IL-6 in a dose-dependent manner.
      Additionally, IL-6 increased gp120-dependent chemotaxis. These results suggest
      that aging increases the sensitivity of mice to behavioral deficits caused by ICV
      gp120, perhaps by increasing expression of CCR5 and augmenting production of
      cytokines.

PMID- 17174452
TI  - Interesting Case: an unusual 'blast' injury.

PMID- 17174451
TI  - [A vertebroplasty with dyspnea].

PMID- 17174453
TI  - Categorization of jaw ameloblastoma based on clinical presentation.

PMID- 17174454
TI  - Incidence of sarcoidosis in head and neck cancer.
AB  - Sarcoidosis and sarcoid-like reactions have been reported to be associated with
      malignancies, particularly testicular cancer and lymphoma. They occur either
      synchronously or metachronously, and may also occur after chemotherapy. We know
      of only two other case reports of granulomatous reactions in head and neck
      cancer. The present case highlights the association of sarcoidosis with head and
      neck cancer, and the importance of considering the diagnosis in patients who may
      have metastatic disease.

PMID- 17174450
TI  - Translational gene mapping of cognitive decline.
AB  - The ability to maintain cognitive function during aging is a complex process
      subject to genetic and environmental influences. Alzheimer's disease (AD) is the
      most common disorder causing cognitive decline among the elderly. Among those
      with AD, there is broad variation in the relationship between AD neuropathology
      and clinical manifestations of dementia. Differences in expression of genes
      involved in neural processing pathways may contribute to individual differences
      in maintenance of cognitive function. We performed whole genome expression
      profiling of RNA obtained from frontal cortex of clinically non-demented and AD
      subjects to identify genes associated with brain aging and cognitive decline.
      Genetic mapping information and biological function annotation were incorporated
      to highlight genes of particular interest. The candidate genes identified in this
      study were compared with those from two other studies in different tissues to
      identify common underlying transcriptional profiles. In addition to confirming
      sweeping transcriptomal differences documented in previous studies of cognitive
      decline, we present new evidence for up-regulation of actin-related processes and
      down-regulation of translation, RNA processing and localization, and vesicle
      mediated transport in individuals with cognitive decline.

PMID- 17174455
TI  - Workload of primary-care midwives.
AB  - OBJECTIVE: to assess the actual workload of primary-care midwives in the
      Netherlands. BACKGROUND: In 2000, a strike and large demonstration before
      parliament convinced everyone of the shortage of midwives and their excessive
      workload. The government reacted by increasing the capacity of the midwifery
      schools and lowering the 'standard caseload' for a full-time working midwife. To
      assess whether this would lead to sufficient improvement of the situation, more
      insight was needed of the actual workload of midwives in primary care. METHOD: a
      4-year prospective survey of the work of primary-care midwives, during 3 weeks
      each year, including all midwives working in a representative sample of midwifery
      practices. On average, 224 midwives participated each year. During 3 weeks in the
      summer and autumn, midwives kept a diary of their work, with an accurate
      timetable, covering 24 hours a day. They also filled out questionnaires about
      practice organisation, work schedules and experiences of workload. FINDINGS:
      primary-care midwives worked an average of 29 hours a week, and about 74% of
      their time (22 hours a week) was spent on client-related activities. On average,
      a midwife was on call during 53 hours a week, and 17 of the 29 hours of work took
      place during on-call-hours. This meant that an average midwife was involved in
      her work 65 hours a week. The time spent on direct client care increased by
      nearly 20%. In particular, the average time spent with a woman during labour and
      birth increased by almost one-third. CONCLUSION: primary-care midwives spend an
      average of 29 hours per week working, and this has remained constant between 2001
      and 2004. In client-related care, there has been a shift towards fewer clients
      per midwife but more time per client.

PMID- 17174457
TI  - Benefits of interhemispheric collaboration can be eliminated by mixing stimulus
      formats that involve different cortical access routes.
AB  - Previous studies indicate that the benefits of dividing an information processing
      load across both cerebral hemispheres outweigh the costs of interhemispheric
      transfer as tasks become more difficult or cognitively complex. This is
      demonstrated as better performance when two stimuli to be compared are presented
      one to each visual field and hemisphere than when both stimuli are presented to
      the same single hemisphere (an across-hemisphere advantage). Two experiments
      indicate that this finding does not generalize to complex tasks that require
      matching numeric quantities represented by two very different visual formats
      whose processing involves somewhat different cortical areas: digits and dice-like
      dot patterns. In fact, mixing these stimulus formats consistently produces a
      within-hemisphere advantage. We propose that, when two simultaneously presented
      stimuli are presented in sufficiently different visual formats, identification of
      the two stimuli may take place in parallel, via different cortical access routes
      and with little or no interference, even when they are presented to the same
      cerebral hemisphere.

PMID- 17174456
TI  - John Henryism, self-reported physical health indicators, and the mediating role
      of perceived stress among high socio-economic status Asian immigrants.
AB  - This study examined the relationship between John Henryism (a strong behavioral
      predisposition to engage in high effort coping with difficult barriers to
      success) and self-reported physical health among high socio-economic (SES) status
      Asian immigrants to the USA. Cross-sectional data were collected from a community
      sample of 318 self-identified Chinese and Indian immigrants aged 18-73, averaging
      10.2 yr lived in the US. In addition to the John Henryism Active Coping Scale,
      health status was measured using ordinal ratings of global self-rated health,
      somatic symptoms and physical health functioning. We also evaluated whether
      perceived stress would explain the relationship between John Henryism and health.
      Controlling for demographic factors, regression analyses showed that higher John
      Henryism significantly predicted better self-rated health and physical
      functioning, and fewer somatic symptoms. These relationships were significantly
      and fully mediated (for physical functioning and somatic symptoms) or partially
      mediated (for self-rated health) by lower perceived stress. Results suggest that
      John Henryism relates to better health among high SES Asian immigrants in part by
      reducing perceived stress. To better understand and improve health in all
      racial/ethnic groups, especially racial minorities and immigrants, more research
      is needed on John Henryism and perceived stress as important psychosocial
      mechanisms intervening between environmental exposures and health outcomes.

PMID- 17174458
TI  - The neural regions sustaining episodic encoding and recognition of objects.
AB  - In this functional MRI experiment, encoding of objects was associated with
      activation in left ventrolateral prefrontal/insular and right dorsolateral
      prefrontal and fusiform regions as well as in the left putamen. By contrast,
      correct recognition of previously learned objects (R judgments) produced
      activation in left superior frontal, bilateral inferior frontal, and right
      cerebellar regions, whereas correct rejection of distractor objects (N judgments)
      was associated with activation in bilateral prefrontal and anterior cingulate
      cortices, in right parietal and cerebellar regions, in the left putamen, and in
      the right caudate nucleus. The R minus N comparison showed activation in the left
      lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while
      the N minus R comparison did not reveal any positive signal change. These results
      support the view that similar regions of the frontal lobe are involved in
      episodic encoding and retrieval processes, and that the successful episodic
      retrieval of newly learned objects is mainly based on a frontoparietal network.

PMID- 17174460
TI  - Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of
      depressed outpatients: a pilot double-blind randomized trial.
AB  - Depression is one of the most common neuropsychiatric conditions, with a lifetime
      prevalence approaching 17%. Although a variety of pharmaceutical agents is
      available for the treatment of depression, psychiatrists find that many patients
      cannot tolerate the side effects, do not respond adequately, or finally lose
      their response. On the other hand, many herbs with psychotropic effects have far
      fewer side effects. They can provide an alternative treatment or be used to
      enhance the effect of conventional antidepressants. A number of recent
      preclinical and clinical studies indicate that stigma and petal of Crocus sativus
      have antidepressant effect. Our objective was to compare the efficacy of petal of
      C. sativus with fluoxetine in the treatment of depressed outpatients in an 8-week
      pilot double-blind randomized trial. Forty adult outpatients who met the DSM- IV
      criteria for major depression based on the structured clinical interview for DSM-
      IV participated in the trial. Patients have a baseline Hamilton Rating Scale for
      Depression score of at least 18. In this double-blind and randomized trial,
      patients were randomly assigned to receive capsule of petal of C. sativus 15 mg
      bid (morning and evening) (Group 1) and fluoxetine 10 mg bid (morning and
      evening) (Group 2) for a 8-week study. At the end of trial, petal of C. sativus
      was found to be effective similar to fluoxetine in the treatment of mild to
      moderate depression (F=0.03, d.f.=1, P=0.84). In addition, in the both
      treatments, the remission rate was 25%. There were no significant differences in
      the two groups in terms of observed side effects. The present study is supportive
      of other studies which show antidepressant effect of C. sativus.

PMID- 17174459
TI  - Right hemispatial neglect: frequency and characterization following acute left
      hemisphere stroke.
AB  - The frequency of various types of unilateral spatial neglect and associated areas
      of neural dysfunction after left hemisphere stroke are not well characterized.
      Unilateral spatial neglect (USN) in distinct spatial reference frames have been
      identified after acute right, but not left hemisphere stroke. We studied 47
      consecutive right handed patients within 48h of left hemisphere stroke to
      determine the frequency and distribution of types of right USN using cognitive
      testing and MRI imaging. The distribution of USN types was different from the
      previously reported distribution following acute right hemisphere stroke. In this
      left hemisphere stroke population, allocentric neglect was more frequent than
      egocentric neglect.

PMID- 17174462
TI  - Comments on "Darwinian models of depression: a review of evolutionary accounts of
      mood and mood disorders" by Nicholas B. Allen, Paul B.T. Badcock. In: progress in
      Neuro-Psychopharmacology and Biological Psychiatry 30 (5) (2006) 815-826.

PMID- 17174461
TI  - Possible levomepromazine-clozapine interaction: two case reports.
AB  - OBJECTIVE: To report and comment upon two cases of suspected pharmacological
      interaction between the "classical" neuroleptic levomepromazine (LMP) and the
      "atypical" antipsychotic clozapine (CLZ). CASE SUMMARY: The patients who
      simultaneously took the two drugs had unusually low plasma levels of CLZ and its
      metabolites, even though they took high doses of CLZ. The patients were
      considered "non-responders" to the treatment by the psychiatrist. When LMP was
      withdrawn from the therapy, plasma concentrations of CLZ returned to therapeutic
      levels and one of the two patients experienced the anticipated therapeutic
      response. DISCUSSION: No information can be found in the literature regarding
      possible interactions between LMP and CLZ. However, the results of the two cases
      reported herein point out to a possible lack of therapeutic efficacy of CLZ
      therapy during this kind of polypharmacy. CONCLUSION: While two cases are too few
      to draw any conclusion, it would be prudent on the part of psychiatrists to
      consider a possible drug interaction in patients receiving both CLZ and LMP who
      fail to respond to the therapy.

PMID- 17174463
TI  - Incipient caries lesions on cementum by mono- and co-culture oral bacteria.
AB  - OBJECTIVES: There is increasing prevalence of root caries. We hypothesized
      different biofilms will cause varying demineralization in cementum. This study
      investigated the extent of demineralization of cementum by oral biofilm formed
      from three major cariogenic microorganisms: Streptococcus mutans, Lactobacillus
      acidophilus, and Actinomyces israelii. Sound cementum tooth blocks were incubated
      with mono-, bi-, and tri-species combinations of the bacteria under
      investigation. MATERIALS AND METHODS: The matrix (amide I) and phosphate content
      of the lesions was analyzed by Fourier-transform infrared spectroscopy (FTIR),
      and calcium and phosphorus levels were analyzed by scanning electron microscopy
      and energy-dispersive spectroscopy (SEM-EDX). RESULTS: The log[amide I:HPO(4)(2-)
      absorbance] values showed that A. israelii mono-culture caused significantly more
      demineralization than the other bacterial cultures. log[Ca:P] showed that all
      carious lesions were confined to the cementum. CONCLUSIONS: Oral biofilm arising
      from bacterial species A. israelii alone was the most cariogenic of those tested
      and produced the most demineralization in incipient carious lesions in cementum.

PMID- 17174464
TI  - Binding of intrinsically disordered proteins is not necessarily accompanied by a
      structural transition to a folded form.
AB  - There are a large number of protein domains and even entire proteins, lacking
      ordered structure under physiological conditions. Intriguingly, a highly
      flexible, random coil-like conformation is the native and functional state for
      many proteins known to be involved in cell signaling. An example is a key
      component of immune signaling, the cytoplasmic region of the T cell receptor zeta
      subunit. This domain exhibits specific dimerization that is distinct from non
      specific aggregation behavior seen in many systems. In this work, we use
      diffusion and chemical shift mapping NMR data to show that the protein does not
      undergo a transition between disordered and ordered states upon dimerization.
      This finding opposes the generally accepted view on the behavior of intrinsically
      disordered proteins, provides evidence for the existence of specific dimerization
      interactions for intrinsically disordered protein species and opens a new line of
      research in this new and quickly developing field.

PMID- 17174465
TI  - Temperature dependence of binding and catalysis for the Cdc25B phosphatase.
AB  - Using a combination of steady-state and single-turnover kinetics, we probe the
      temperature dependence of substrate association and chemistry for the reaction of
      Cdc25B phosphatase with its Cdk2-pTpY/CycA protein substrate. The transition
      state for substrate association is dominated by an enthalpic barrier (DeltaH(++)
      of 13 kcal/mol) and has a favorable entropic contribution of 4 kcal/mol at 298 K.
      Phosphate transfer from Cdk2-pTpY/CycA to enzyme (DeltaH(++) of 12 kcal/mol) is
      enthalpically more favorable than for the small molecule substrate p-nitrophenyl
      phosphate (DeltaH(++) of 18 kcal/mol), yet entropically less favorable
      (TDeltaS(++) of 2 vs. -6 kcal/mol at 298 K, respectively). By measuring the
      temperature dependence of binding and catalysis for several hotspot mutants
      involved in binding of protein substrate, we determine the enthalpy-entropy
      compensations for changes in rates of association and phosphate transfer compared
      to the wild type system. We conclude that the transition state for enzyme
      substrate association involves tight and specific contacts at the remote docking
      site and that phospho-transfer from Cdk2-pTpY/CycA to the pre-organized active
      site of the enzyme is accompanied by unfavorable entropic rearrangements that
      promote rapid product dissociation.

PMID- 17174466
TI  - Prediction of pathological stage is inaccurate in men with PSA values above 20
      ng/mL.
AB  - INTRODUCTION: We hypothesized that either very low (0-2.5 ng/mL) or very high
      (>20 ng/mL) PSA values may limit the accuracy of pathological stage predictions.
      To test this hypothesis, we examined 5193 consecutive patients subjected to
      radical prostatectomy (RP) for localized prostate cancer (PCa). MATERIAL AND
      METHODS: Patients were divided into three cohorts according to their pre
      treatment PSA value: </=2.5 (n=331), 2.51-20 (n=4545) and >20 ng/mL (n=317).
      Subsequently in each cohort, the ability of PSA, clinical stage and biopsy
      Gleason sum was tested in multivariable logistic regression models predicting
      three separate endpoints: extracapsular extension (ECE), seminal vesicle invasion
      (SVI) and lymph node invasion (LNI). Predictive accuracy represented the
      performance benchmark. All models were adjusted for year of surgery and subjected
      to 200 bootstrap resamples to reduce overfit bias. RESULTS: For PSA </=2.5 ng/mL,
      predictive accuracy was 76.7%, 72.3% and 82.8% for respectively ECE, SVI and LNI.
      For PSA 2.51-20 ng/mL, the predictive accuracy for the same endpoints was 67.8%,
      77.4% and 81.6%. Finally, for PSA >20 ng/mL, predictive accuracy was 63.6%, 63.7%
      and 70.6%. CONCLUSIONS: The ability to predict pathological stage in patients
      with PSA values in excess of 20 ng/mL significantly decreased, compared to
      patients with lower PSA values. Therefore, accurate staging of these patients may
      require alternative markers or staging schemes.

PMID- 17174467
TI  - Seasonality of serum prostate-specific antigen levels: a population-based study.
AB  - OBJECTIVE: The measurement of PSA serum levels is central to all early detection
      programs for prostate cancer. Although individual PSA values were known to
      fluctuate in the short and long term, the influence of insolation and seasons on
      PSA had not been addressed to date. To assert the relationship between total and
      free PSA and meteorological data in 8644 participants (55-70 years) in the French
      arm of the ERSPC study. METHODS: Blood sample was taken at the local laboratory
      after informed consent and frozen sera were sent for central testing of total and
      free PSA. PSA measurement was performed within 7 days on the Access 1.0 automat
      with Hybritech reagents. Monthly meteorological data -- insolation, daily
      temperatures and rain precipitations -- were obtained from the local branches of
      the National Meteorology Agency. RESULTS: Total PSA -- but not free PSA -- was
      correlated with insolation, that is the monthly accrual in hours of sunshine
      during which the intensity was higher than 120 Watt x m(-2) (r = 0.05 (95%CI:
      0.03-0.07; p < 0.0001)) while no relationships were shown between insolation and
      percent-free PSA (free PSA divided by the total PSA). Interdependence between
      total PSA and insolation was also apparent with respect to the 3 ng/mL ERSPC
      cutoff for recommending biopsies (213.1 vs. 206.2 hours, p = 0.004). Such
      relationship was even more evident in summer when the tested participants more
      often had a PSA > 3 ng/mL (17.1% vs. 14.3%, p = 0.0006) than in the rest of the
      year, resulting in 23% more chances of being referred for biopsies (Odds ratio
      1.23, 95%CI: 1.10-1.40). CONCLUSIONS: Total PSA was shown to be strongly
      associated with insolation and seasons while the percent-free PSA was not
      influenced.

PMID- 17174468
TI  - A patient with neuro-Behcet's disease is successfully treated with etanercept:
      further evidence for the value of TNFalpha blockade.
AB  - Behcet's disease is a chronic relapsing multisystem vasculitis with 49% of cases
      involving the CNS. Recently there have been two reports of neuro-Behcet's disease
      (NB) successfully treated with the tumour necrosis factor alpha (TNFalpha)
      monoclonal antibody infliximab. We describe a patient with longstanding NB who
      was poorly responsive to azathioprine, cyclosporin, thalidomide and methotrexate.
      She showed a remarkable response when treated with the recombinant human TNFalpha
      receptor protein, etanercept. To the best of our knowledge this is the first
      report of NB successfully treated with etanercept.

PMID- 17174469
TI  - Preparation of xylenol orange functionalized silica gel as a selective solid
      phase extractor and its application for preconcentration--separation of mercury
      from waters.
AB  - A new selective solid phase extractor was prepared from silica gel modified with
      xylenol orange (SGMXO). The solid phase extractor is stable in 6molL(-1) HCl,
      common organic solvents, and pH 1.0-9.0 buffer solutions. In the batch
      experiments, Hg(II) can be adsorbed on SGMXO at pH 1.0 with 90.0% retention,
      whereas the retention of other common coexisting metal ions such as Cd(II),
      Pb(II), Cu(II), Ni(II), Co(II), Mn(II), Zn(II), and Fe(III) is less than 4.1%..
      The adsorption equilibration for Hg(II) was achieved within 3min. At optimum
      conditions, the adsorption capacity of the extractor is 18.26micromolg(-1) of dry
      modified silica gel, and the preconcentration factor is as high as 333. The
      recovery is still higher than 95% for the preconcentration of 10ngmL(-1) Hg(II).
      The new solid phase extractor has been used for the preconcentration of low level
      of Hg(II) in surface water, tap water in chemistry laboratory and student's
      dormitory and a simulated sea water samples, recoveries of 98.2-100.6% were
      obtained. It is showed that low level of Hg(II) can be effectively
      preconcentrated by this new selective solid phase extractor.

PMID- 17174470
TI  - Inhibition by bis(7)-tacrine of native delayed rectifier and KV1.2 encoded
      potassium channels.
AB  - Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] acts as an AChE inhibitor and also
      exerts modulatory effects on many ligand-gated ion channels and voltage-gated
      Ca(2+) and K(+) channels. It has been reported previously that tacrine and some
      other AChE inhibitors suppressed I(K(A)) in central and peripheral neurons. The
      present study aimed to explore whether bis(7)-tacrine could modulate the function
      of native delayed rectifier potassium channels in DRG neurons and K(V)1.2 encoded
      potassium channels expressed in oocytes. We found that both delayed rectifier
      potassium currents (I(K(DR))) in rat DRG neurons and the currents recorded from
      oocytes expressing K(V)1.2 (I(K(K(V)1.2))) were suppressed by bis(7)-tacrine, the
      potency of which was two orders greater than that of tacrine. The IC(50) values
      for bis(7)-tacrine and tacrine inhibition of I(K(KD)) in DRG neurons were 0.72+/
      0.05 and 58.3+/-3.7 microM, respectively; while the two agents inhibited
      I(K(K(V)1.2)) in oocytes with an IC(50) of 0.24+/-0.06 and 102.1+/-21.5 microM,
      respectively. The possible mechanism for bis(7)-tacrine inhibition of I(K(A)) and
      I(K(K(V)1.2)) was identified as the suppression of their activation,
      inactivation.

PMID- 17174471
TI  - Upregulation of the chemokine monocyte chemoattractant protein-1 following
      unilateral nerve injury in the peripheral taste system.
AB  - Macrophages are recruited to both sides of the tongue following unilateral chorda
      tympani (CT) nerve injury. The mechanisms responsible for recruiting these
      macrophages to the peripheral taste system are unknown. Neural degeneration in
      other systems leads to the upregulation of small molecules that function as
      chemoattractant cytokines, or chemokines. The chemokines monocyte chemoattractant
      protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha are important
      regulators of macrophage recruitment to sites of infection and injury. We
      hypothesized that CT nerve sectioning leads to a bilateral upregulation of MCP-1
      and MIP-1alpha. We examined lingual protein levels of MCP-1 and MIP-1alpha by
      enzyme-linked immunosorbent assays (ELISA)s at several time points after
      unilateral CT section in rats. MCP-1 was significantly upregulated on the intact
      side of the tongue at 12 h after sectioning, and on the injured side at 24-48 h
      post-injury. However, MIP-1alpha expression did not significantly change
      following CT nerve sectioning. These data indicate that chemokines are
      differentially regulated following neural injury, and that MCP-1 may contribute
      to the bilateral macrophage response to neural injury. Furthermore, the increase
      in MCP-1 occurs even in uninjured, distant sites, and may be upstream from the
      deficits in neural responses from the contralateral CT after sectioning.

PMID- 17174472
TI  - Effect of 2,4-dinitrophenol under non-oxygenated condition in pons-medulla-spinal
      cord preparations in newborn rats: comparison with medulla-spinal cord
      preparations.
AB  - We tested whether depression of respiratory frequency (fR) under non-oxygenated
      artificial cerebrospinal fluid (aCSF) in pons-medulla-spinal cord (PMS) and
      medulla-spinal cord (MS) preparations is significantly influenced by the
      mitochondrial uncoupler 2,4-dinitrophenol (2,4-DNP) in newborn rats. Preparations
      were obtained from 0- to 4-day-old rats, and fR was monitored at the C4 ventral
      root in environmental temperature (24 degrees C). 2,4-DNP was dissolved in aCSF
      (1, 10 or 30 microM; pH 7.4), and we measured fR in PMS (n=19) and MS (n=16),
      both of which were superfused with aCSF equilibrated with oxygenated (95% O2-5%
      CO2) or non-oxygenated (10% O2-5% CO2, balanced with pure N2) gas. Our results
      showed that: (1) fR was significantly lower in PMS than MS, (2) fR was
      significantly decreased under non-oxygenated aCSF in both PMS and MS and (3) fR
      under non-oxygenated aCSF was significantly increased by 2,4-DNP applications at
      10 and 30 microM in PMS but not in MS. Our results suggest that depression in fR
      under non-oxygenated aCSF in PMS and MS may not be due simply to O2 limitation,
      and 2,4-DNP has a stimulant effect on the medullary respiratory rhythm generator
      (RRG) through pontine RRG regulatory mechanisms under non-oxygenated aCSF.

PMID- 17174473
TI  - Effect of post-hypoxic reoxygenation on DNA fragmentation in cortical neuronal
      nuclei of newborn piglets.
AB  - Previous studies have shown an increased fragmentation of genomic DNA following
      hypoxia in cortical neuronal nuclei of newborn piglets. The present study tests
      the hypothesis that DNA fragmentation following hypoxia persists during
      reoxygenation in cortical neuronal nuclei of newborn piglets. To test this
      hypothesis, DNA fragmentation was assessed in 36 newborn piglets divided into six
      groups: normoxic (Nx), hypoxic (Hx) and hypoxic/reoxygenated for 6, 12, 24h and 7
      days. The Hx groups were exposed to 7% oxygen for 1h followed by reoxygenation to
      room air for 6, 12, 24h and 7 days. Cerebral tissue hypoxia was confirmed
      biochemically by ATP and phosphocreatine (PCr) levels. Nuclei were isolated and
      purified using discontinuous sucrose gradient. DNA was isolated by
      phenol/chloroform/isoamyl-alcohol extraction method. ATP/PCr (micromol/g brain)
      were 4.11+/-0.15/3.67+/-0.30 for Nx, 1.31+/-0.68/0.74+/-0.30 for Hx, 3.81+/
      0.11/3.24+/-0.14 for 6h reoxygenation, 4.21+/-0.12/3.27+/-0.09 for 12h
      reoxygenation and 4.63+/-0.09/3.75+/-0.27 for 24h reoxygenation and 4.31+/
      0.12/3.70+/-0.21 for 7 days reoxygenation. There was a significant difference in
      the ATP and PCr values between Nx and Hx groups (p<0.05) and between Hx and
      hypoxic reoxygenated groups (p<0.05). DNA fragments (OD/mm(2)) increased from
      1776+/-267 in the Nx group to 3211+/-285 in the Hx group (p<0.05). In the
      reoxygenation groups, DNA fragments (OD/mm(2)) decreased to 2018+/-249 after 6h
      (p<0.05 versus Hx) but increased to 3408+/-206, 2782+/-406 and 3256+/-302 after
      12, 24h and 7 days, respectively. The data show a decrease in DNA fragmentation
      in the early phase (6h) of reoxygenation but is comparable to acute hypoxia
      during the later phases (12, 24h and 7 days) of reoxygenation. We propose that
      the biphasic pattern of DNA fragmentation during reoxygenation occurs by an
      initial oxidative DNA injury followed by an enzymatic cleavage of DNA by
      endonucleases activation.

PMID- 17174475
TI  - No association between Parkinson's disease and three polymorphisms in the eNOS,
      nNOS, and iNOS genes.
AB  - Nitric oxide synthases (NOS) and mitochondrial DNA-polymorphisms have been
      associated with the risk of developing Parkinson's disease (PD). In this report,
      we genotyped 450 PD-patients and 200 controls for three polymorphisms in the
      endothelial, inducible and neuronal NOS-genes, and for the T4336C and A10398G
      mitochondrial DNA-polymorphisms. None of the eNOS (intron 4 VNTR), iNOS (exon 22
      A/G), or nNOS (exon 29T/C) were significantly associated with PD. Mitochondrial
      4336C increased the PD-risk among women (OR=6.13), while the 10398G had a
      protective effect (OR=0.52). We did not find significantly interactions between
      the NOS and mitochondrial polymorphisms in the risk for PD in our population.

PMID- 17174474
TI  - Effects of carbonic anhydrase VIII deficiency on cerebellar gene expression
      profiles in the wdl mouse.
AB  - Recently, the waddles (wdl) mouse was identified as a carbonic anhydrase VIII
      (Car8) mutant. The mutation is associated with marked deficiency of Car8, an
      inositol triphosphate receptor 1-binding protein expressed at high levels in
      cerebellar Purkinje cells. To help unravel the molecular aberrations contributing
      to motor dysfunction in wdl mice, cerebellar gene expression profiles were
      examined in the mutants and their wild-type littermates. Genes involved in
      signaling, cell division, zinc ion-binding, synapse integrity and plasticity were
      downregulated in wdl mice. Several of the upregulated genes encode proteins that
      function in the Golgi apparatus which suggests that Car8 deficiency has important
      effects on synaptic vesicle formation and transport.

PMID- 17174476
TI  - Risperidone reduces mRNA expression levels of Sulfonylurea Receptor 1 and TASK1
      in PC12 cells.
AB  - Electrophysiological and immunohistochemical studies have demonstrated that
      glucose-sensing neurons in the hypothalamus contain both ATP-sensitive K(+)
      (K(ATP)) and tandem-pore K(+) (TASK1 and TASK3) channels and that glucose-induced
      depolarization or hyperpolarization of these neurons function as an important
      link between glucose-excited or glucose-inhibited neurons and feeding behavior.
      Medication with atypical antipsychotics increases the appetite of schizophrenic
      patients and thus causes increases in body weight. Therefore, the present study
      investigates mRNA expression levels of the genes encoding the components of these
      K(+) channel subsets in PC12 cells cultured with risperidone (an atypical
      antipsychotic) and in the hypothalami of rats subcutaneously injected for 21
      consecutive days with 0.1 or 0.01 mg/kg/day of risperidone. The mRNA expression
      levels of various genes were not obviously altered in rat hypothalami. However,
      the mRNA expression levels for sulfonylurea receptor 1, a component affording
      nucleotide-binding folds to K(ATP) channels, and TASK1 were down-regulated in
      PC12 cells cultured with 50 microM risperidone for 24h, but the amount of
      intracellular ATP in these cells was not affected by the drug. Collectively,
      these results indicate that the amplitude of the current through these K(+)
      channels in PC12 cells might be modulated as a pharmacological effect of
      risperidone.

PMID- 17174477
TI  - Neurological soft signs and cerebral measurements investigated by means of MRI in
      schizophrenic patients.
AB  - Neurophysiologic research has shown a Neurological Soft Sign (NSS) characteristic
      prevalence in schizophrenic patients, and correlations between NSS and the most
      frequently cerebral alterations. The aim of this study was to investigate, by
      means of MRI, the quantitative alterations of cortical and subcortical structures
      and their correlation with NSS in a sample of schizophrenic patients. Linear
      measures of lateral ventricular (Evans ratio), third ventricular (Third
      Ventricular Width), hippocampal (Interuncal Index) and cerebellar (Verm
      Cerebellar Atrophy) atrophy were made on magnified MR images of 33 patients with
      a DSM IV diagnoses of chronic schizophrenia. NSS were evaluated with the Buchanan
      and Heinrichs's Neurological Evaluation Scale (NES). Lateral ventricular
      enlargement showed to be correlated with right stereoagnosia item (p=0.001).
      Hippocampal atrophy, with right stereoagnosia item (p=0.023), with forefinger
      right thumb opposition (p=0.004), forefinger-left thumb opposition (p=0.029 and
      face-hand extinction (0.26). Third ventricle enlargement showed to be correlated
      with forefinger-right thumb opposition (p=0.001), forefinger-left thumb
      opposition(p=0.021) and total sensorial integration (p=0.012). Cerebellar atrophy
      showed to be correlated with rhythmic drumming item (p=0.042), forefinger-right
      thumb opposition (p=0.007), forefinger-left thumb opposition (p=0.026), left
      specular movements (p=0.049), face-hand extinction (p=0.001), right-left
      confusion (p=0.005) and with left forefinger-nose index (p=0.032). Results
      obtained confirm the correlation between NSS and neuroanatomical alterations in
      schizophrenia.

PMID- 17174479
TI  - Regulation of neurite growth in immortalized mouse hypothalamic neurons and rat
      hippocampal primary cultures by teneurin C-terminal-associated peptide-1.
AB  - Teneurins are a highly conserved family of four type II transmembrane proteins
      that are expressed in the CNS. The protein possesses several functional domains
      including a unique bioactive 40-41 amino acid sequence at the extracellular
      terminus. Synthetic versions of this teneurin C-terminal-associated peptide
      (TCAP) can modulate cyclic AMP accumulation, cell proliferation and teneurin mRNA
      levels in vitro. Furthermore, i.c.v. injections of TCAP-1 into rat brain induce
      major changes in acoustic startle response behavior 3 weeks after administration,
      suggesting that the peptide may act to alter interneuron communication via
      changes in neurite and axon outgrowth. Synthetic mouse/rat TCAP-1 was used to
      treat cultured immortalized mouse hypothalamic cells, to determine if TCAP-1
      could directly regulate neurite and axon growth. TCAP-1-treated cells showed a
      significant increase in the length of neurites accompanied by a marked increase
      in beta-tubulin transcription and translation as determined by real-time PCR and
      Western blot analysis, respectively. Changes in alpha-actinin-4 transcription and
      beta-actin protein expression were also noted. Immunofluorescence confocal
      microscopy using beta-tubulin antiserum showed enhanced resolution of beta
      tubulin cytoskeletal elements throughout the cell. In order to determine if the
      effects of TCAP-1 could be reproduced in primary neuronal cultures, primary
      cultures of E18 rat hippocampal cells were treated with 100 nM TCAP-1. The TCAP-1
      treated hippocampal cultures showed a significant increase in both the number of
      cells, dendritic branching and the presence of large and fasciculated beta
      tubulin immunoreactive axons. These data suggest that TCAP acts, in part, as a
      functional region of the teneurins to regulate neurite and axonal growth of
      neurons.

PMID- 17174480
TI  - A comparison of craving and emotional states between pathological gamblers and
      alcoholics.
AB  - Fifty pathological gamblers and 42 alcohol dependent subjects were compared
      regarding craving, emotional states and social functioning. Subjects self-rated
      their cravings using the Weiss Craving Scale (WCS) and the Pennsylvania Craving
      Scale (PCS). Subjects answered a semi-structured interview, the Positive and
      Negative Affect Scale Extended Form (PANAS-X), and the Social Adjustment Scale
      (SAS-SR). Gamblers had higher scores on craving measures. Regression models
      showed that craving for gambling and alcohol have a significant correlation with
      emotional states. Craving for gambling was inversely correlated with positive
      affect and craving for alcohol was directly correlated with negative affect.
      Gambling craving was more dependent upon external factors and related to an
      unpleasant dearousing state, while alcohol craving was associated with an
      unpleasant arousing state. These findings point to the key role of emotional
      deregulation on gambling and alcohol cravings following early abstinence.

PMID- 17174482
TI  - Modification of Lactobacillus beta-glucuronidase activity by random mutagenesis.
AB  - The Lactobacillus gasseri ADH beta-glucuronidase gene, gusA, was cloned
      previously and found to exhibit excellent activity in acidic pH ranges, with
      maximal activity at pH 5.0. In contrast, activity was limited in neutral pH
      ranges of 6-7. In an effort to improve the activity of the reporter enzyme in
      neutral pH ranges, the gusA gene was cloned into the broad host range vector,
      pGK12, and subjected to random mutagenesis by passage through Epicurian coli
      mutator strain XL1-Red. Two mutant alleles, gusA2 and gusA3, were recovered that
      produced beta-glucuronidase with increased activity in neutral pH ranges. One of
      these, gusA3, was significantly more active in the pH range of 4-8 in both
      Escherichia coli and L. gasseri. Sequence analysis of gusA2 and gusA3 revealed
      single base pair changes that resulted in D524G and D573A substitutions,
      respectively. The modified GusA3 enzyme has expanded potential for use as a
      reporter enzyme in expression hosts that are not acidophilic, as well as lactic
      acid bacteria and other microorganisms that grow in acidifying environments.

PMID- 17174481
TI  - Non-injection drug use and Hepatitis C Virus: a systematic review.
AB  - This systematic review examined the evidence on the prevalence of the Hepatitis C
      Virus (HCV) in non-injecting drug users (NIDUs) who sniff, smoke or snort drugs
      such as heroin, cocaine, crack or methamphetamine. The search included studies
      published from January 1989 to January 2006. Twenty-eight eligible studies were
      identified and the prevalence of HCV in these NIDU populations ranged from 2.3 to
      35.3%. There was substantial variation in study focus and in the quality of the
      NIDU data presented in the studies. The results of our systematic review
      suggested that there are important gaps in the research of HCV in NIDUs. We
      identified a problem of study focus; much of the research did not aim to study
      HCV in users of non-injection drugs. Instead, NIDUs were typically included as a
      secondary research concern, with a principal focus on the problem of transmission
      of HCV in IDU populations. Despite methodological issues, HCV prevalence in this
      population is much higher than in a non-drug using population, even though some
      IDUs might have inadvertently been included in the NIDU samples. These studies
      point to a real problem of HCV in NIDU populations, but the causal pathway to
      infection remains unclear.

PMID- 17174478
TI  - Developing master keys to brain pathology, cancer and aging from the structural
      biology of proteins controlling reactive oxygen species and DNA repair.
AB  - This review is focused on proteins with key roles in pathways controlling either
      reactive oxygen species or DNA damage responses, both of which are essential for
      preserving the nervous system. An imbalance of reactive oxygen species or
      inappropriate DNA damage response likely causes mutational or cytotoxic outcomes,
      which may lead to cancer and/or aging phenotypes. Moreover, individuals with
      hereditary disorders in proteins of these cellular pathways have significant
      neurological abnormalities. Mutations in a superoxide dismutase, which removes
      oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral
      sclerosis. Additionally, DNA repair disorders that affect the brain to various
      extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner
      syndrome. Here, we highlight recent advances gained through structural
      biochemistry studies on enzymes linked to these disorders and other related
      enzymes acting within the same cellular pathways. We describe the current
      understanding of how these vital proteins coordinate chemical steps and integrate
      cellular signaling and response events. Significantly, these structural studies
      may provide a set of master keys to developing a unified understanding of the
      survival mechanisms utilized after insults by reactive oxygen species and
      genotoxic agents, and also provide a basis for developing an informed
      intervention in brain tumor and neurodegenerative disease progression.

PMID- 17174483
TI  - Functional splice sites in a zebrafish LINE and their influence on zebrafish gene
      expression.
AB  - Long interspersed elements (LINEs) are transposable elements that exist in many
      kinds of eukaryotic genomes, where they have a large effect on genome evolution.
      There are several thousands to hundreds of thousands of LINE copies in each
      eukaryotic genome. LINE elements are amplified by a mechanism called
      retrotransposition, in which a LINE-encoded protein reverse transcribes (copies)
      its own RNA. We previously isolated two retrotransposition-competent LINEs, ZfL2
      1 and ZfL2-2, from zebrafish. Although it has generally been thought that LINEs
      do not have 'introns' (because the LINE RNA is used as the template during
      retrotransposition), we now show that these two LINEs contain multiple putative
      functional splice sites. We further show that at least one pair of these splice
      sites is actually functional in zebrafish cells. Moreover, some of these splice
      sites are coupled with the splicing signal of a host endogenous gene, thereby
      generating a new chimeric spliced mRNA variant for this gene. Our results suggest
      the possible role of these LINE splice sites in modulating retrotransposition and
      host gene expression.

PMID- 17174484
TI  - Genome-wide analysis of factors regulating gene expression in liver.
AB  - In recent decades, multiple individual genes have been studied with respect to
      their level of expression in liver tissue and in many cases substantial progress
      has been made in identifying individual factors promoting gene expression in
      liver. However, the overall picture is still undefined and general rules or
      factors regulating gene expression in liver have not yet been established. Thus,
      a genome-wide screen for factors regulating gene expression in liver is of high
      interest, as it may reveal common regulatory mechanisms for most genes highly
      expressed in liver. These factors represent potential new targets in liver
      disease associated with differential gene expression. Using a novel
      bioinformatics approach, we have performed a genome-wide, bioinformatic screen to
      identify genetic factors regulating gene expression in liver. As the expression
      of an individual gene is generally driven by its promoter activity, we compared
      the level of expression to individual promoter sequences. Expression data of
      15,704 individual genes in 12 tissues were obtained from a normal tissue
      microarray dataset. The genes were subsequently divided into two groups,
      according to whether or not their highest expression level was found in liver
      tissue. Scanning 1000 bp upstream of the transcription start of each individual
      gene and using the PromoterScan algorithm, we were able to identify a total of
      7042 promoters containing a total of 241,984 transcription factors. To eliminate
      the possibility that currently unknown transcription factors may be crucial to
      liver expression regulation, we investigated all possible nucleotide combinations
      of 8 bp and 10 bp which we reasoned may serve as novel binding sites for
      transcription factors. In both screens we did not detect any significant,
      biologically relevant differences in numbers of transcription factors and binding
      sites between the two groups. Furthermore, we excluded possible differences in
      distribution of TATA-boxes or CpG islands as well as differences in nucleotide
      composition of RNA sequences or amino acid composition of transcribed protein
      sequences. We conclude that the existence of central, superordinated regulatory
      factors in liver gene expression is unlikely and that expression of individual
      genes in liver is more likely to be dependent on individual combinations of
      regulating factors for each gene.

PMID- 17174485
TI  - Genetic characterisation of African swine fever viruses from outbreaks in
      southern Africa (1973-1999).
AB  - African swine fever (ASF) is a highly lethal and economically significant disease
      of domestic pigs in the southern African sub-region, where outbreaks regularly
      occur. There is anecdotal evidence suggesting that trans-boundary movement of
      infected animals may have played a role in precipitating widespread outbreaks in
      the past, however, since the 1970s outbreaks have generally been more localised,
      particularly in those countries where control of animal movement is strictly
      regulated. The origin and relatedness of regional ASF outbreaks was investigated
      here by means of a two-step genetic characterisation approach whereby p72 gene
      sequencing was used to delineate genotypes, prior to intra-genotypic resolution
      of viral relationships by central variable region (CVR) characterisation of the
      9RL ORF. In this manner, regional virus heterogeneity and epidemiological links
      between outbreaks could be assessed for the first time through phylogenetic
      analysis of the C-terminal end of the p72 gene of viruses recovered from domestic
      pig outbreaks in southern Africa between 1973 and 1999. The phylogeny revealed
      the presence of 14 distinct p72 genotypes of which 6 (genotypes XVII-XXII) were
      considered novel. Eight of these were country-specific with the remaining six
      having a trans-boundary distribution. CVR products were heterogeneous in size
      ranging from 377bp to 533bp across the 14 southern African genotypes. Within
      genotype CVR comparisons revealed the presence of a genotype XIX virus with an
      extended field presence in South Africa (1985-1996) and permitted discrimination
      between three genotype VII viruses that were identical across the p72 gene.

PMID- 17174486
TI  - Formation and biochemistry of carcinogenic heterocyclic aromatic amines in cooked
      meats.
AB  - Heteroyclic aromatic amines (HAAs) are a class of hazardous chemicals that are
      receiving heightened attention as a risk factor for human cancer. HAAs arise
      during the cooking of meats, fish, and poultry, and several HAAs also occur in
      tobacco smoke condensate and diesel exhaust. Many HAAs are carcinogenic and
      induce tumors at multiple sites in rodents. A number of epidemiologic studies
      have reported that frequent consumption of well-done cooked meats containing HAAs
      can result in elevated risks for colon, prostate, and mammary cancers. Moreover,
      DNA adducts of HAAs have been detected in human tissues, demonstrating that HAAs
      induce genetic damage even though the concentrations of these compounds in cooked
      meats are generally in the low parts-per-billion (ppb) range. With recent
      improvements in sensitivity of mass spectrometry instrumentation, HAAs, their
      metabolites, and DNA adducts can be detected at trace amounts in biological
      fluids and tissues of humans. The incorporation of HAA biomarkers in epidemologic
      studies will help to clarify the role of these dietary genotoxicants in the
      etiology of human cancer.

PMID- 17174487
TI  - Plasma phenylacetate and 1-naphthyl acetate hydrolyzing activities of wild birds
      as possible non-invasive biomarkers of exposure to organophosphorus and carbamate
      insecticides.
AB  - Organophosphorus and carbamate insecticides inhibit the carboxylesterases found
      in plasma. Therefore, these carboxylesterases might be used as biomarkers of
      exposure to these insecticides. This work initiates the characterization of the
      phenylacetate (PA) and 1-nafthylacetate (NA) hydrolyzing activities (PAase and
      NAase) in the plasma of 11 different wild bird species and aims to determine
      their suitability as biomarkers of exposure. PAase activity values, expressed as
      mumol product/30min/mL plasma, ranged between 38+/-2.3 (black vulture) and 27+/
      0.85 (barn owl), while NAase values ranged between 6.0+/-5.2 (griffon vulture)
      and 38+/-0.85 (barn owl). In all assayed species, NAase was between 1.1 and 2.8
      times higher than the corresponding PAase. PAase and NAase of chicken white stork
      were 1.6 and 1.7 times higher, respectively, than the corresponding activities of
      adult individuals. Nocturnal raptors, eagle owl and barn owl, exhibited PAase and
      NAase between 1.3 and 8.0 times higher than activities exhibited by diurnal
      raptors (Montagu's harrier, common buzzard, booted eagle, Spanish imperial eagle,
      black kite, griffon vulture and black vulture). Data presented in this work
      suggest that plasma PAase and NAase of the studied birds might be used as
      biomarkers of exposure to organophosphorus and carbamate insecticides, although
      further studies of inhibition of these activities are still needed.

PMID- 17174488
TI  - Evaluation of the three most commonly used analytical methods for determination
      of inorganic arsenic and its metabolites in urine.
AB  - This work compares the three most common analytical methods for determination of
      inorganic arsenic and its metabolites in urine: high performance liquid
      chromatography coupled to either inductively coupled plasma mass spectrometry or
      atomic fluorescence spectrometry via hydride generation (high performance liquid
      chromatography-hydride generation-inductively coupled plasma mass spectrometry
      (HPLC-HG-ICPMS) and HPLC-HG-atomic fluorescence spectrometry (AFS), respectively)
      and atomic absorption spectrometry coupled to HG (HG-atomic absorption
      spectrometry (AAS)). This was done with the focus to find alternatives to ICPMS,
      the investment and running costs of which are rather high. Between-laboratory
      comparison of HPLC-HG-ICPMS and HPLC-HG-AFS showed good agreement for inorganic
      arsenic, methylarsonate (MA) and dimethylarsinate (DMA) (R(2)=0.91, R(2)=0.92 and
      R(2)=0.90, respectively, N=86). Within-laboratory comparisons of HPLC-HG-AFS,
      HPLC-HG-ICPMS and HG-AAS showed good agreement for all arsenic species and the
      sum of inorganic arsenic and its metabolites in urine (HPLC-HG-ICPMS versus HPLC
      HG-AFS: R(2)=0.95; HG-AAS versus HPLC-HG-AFS: R(2)=0.95 and HPLC-HG-ICPMS versus
      HG-AAS: R(2)=0.97; N=89). HPLC-HG-AFS was found to be a simple, but high quality
      alternative to HPLC-HG-ICPMS for the speciation and quantification of inorganic
      arsenic and its metabolites in urine at arsenic concentrations above 10microgL(
      1). Because of its considerably lower costs compared to HPLC-HG-ICPMS, it may be
      a good alternative in laboratories where the high cost of ICPMS is not justified
      in relation to the intended use of the instrument.

PMID- 17174490
TI  - Recovery of large preantral follicles from buffalo ovary: effect of season and
      corpus luteum.
AB  - Preantral follicle can be considered as an alternative source of oocyte for in
      vitro production of embryos. The objective of the present study was to
      standardize a procedure for the isolation of large preantral follicles (>150-500
      microm) from buffalo ovaries and to determine the effect of season and the
      presence of corpus luteum on the recovery rate of the large preantral follicles.
      A combined enzymatic cum mechanical approach was adopted to recover the large
      preantral follicles. In the first experiment, the ovarian cortical pieces were
      suspended in trypsin (1000-1500 BAEE units for milligrams of solid) and incubated
      at various temperatures for different periods, i.e. (1) trypsin (1%), 37 degrees
      C for 10 min; (2) trypsin (1%), 37 degrees C for 10 min + 4 degrees C for 3 h;
      (3) trypsin (0.5%), 37 degrees C for 20 min; (4) trypsin (0.25%), 37 degrees C
      for 20 min. Although there was no significant difference (P>0.05) among the
      different protocols, the first protocol yielded more follicles (3.2, 2.6, 1.8 and
      1.5 per ovary, respectively). Hence, the first protocol was selected and used in
      the second and third experiments. In the second experiment, the effect of season,
      i.e. peak breeding season (October-March) versus low breeding season (April
      September) was evaluated on the recovery rate of the large preantral follicles.
      The recovery rate of large preantral follicles from the ovaries during the peak
      breeding season was significantly (P<0.05) greater (9.92+/-0.85 per ovary) than
      that of the low breeding season (4.95+/-0.27 per ovary). In the third experiment,
      effect of the presence of corpus luteum on the recovery rate of large preantral
      follicles was studied. There was a significantly (P<0.05) higher yield of large
      preantral follicles from the ovaries with corpus luteum (8.05+/-0.88 per ovary)
      than for the ovaries without corpus luteum (4.57+/-0.43 per ovary). This study
      confirms that the large preantral follicles can be isolated from buffalo ovaries
      using a combination of enzymatic cum mechanical methods and that more large
      preantral follicles can be recovered during the peak breeding season and from the
      ovaries having corpus luteum.

PMID- 17174489
TI  - The effects of GnRH analogue (buserelin) or hCG (Chorulon) on Day 12 of pregnancy
      on ovarian function, plasma hormone concentrations, conceptus growth and
      placentation in ewes and ewe lambs.
AB  - The objectives of this study were to determine the effect of GnRH analogue
      (buserelin) or human chorionic gonadotrophin (hCG, Chorulon) treatment on Day 12
      of pregnancy on ovarian function, plasma hormone concentrations, conceptus growth
      and placentation in ewes and ewe lambs. After oestrus synchronization with
      progestagen sponges and eCG, all the animals were mated with fertile rams. Both
      ewes and ewe lambs (20 per treatment group) were given either normal saline or 4
      microg GnRH or 200 IU hCG on Day 12 post-mating. Pre- and post-treatment plasma
      hormone concentrations were determined in seven pregnant animals per treatment
      group in samples collected 1h before and 0, 2, 4, 6, 8, 24, 48 and 72 h after
      treatment. Overall mean progesterone concentrations were higher (P<0.001) in ewes
      as compared with ewe lambs in saline-treated controls. GnRH or hCG treatment
      increased (P<0.001) mean plasma progesterone concentrations in both age groups,
      however, post-treatment concentrations were significantly (P<0.05) higher in ewes
      than in ewe lambs. Oestradiol concentrations were similar in the two control
      groups. In ewes, but not in ewe lambs, both GnRH and hCG treatments significantly
      (P<0.05) increased the mean oestradiol concentrations above pre-treatment levels.
      Moreover, post-treatment oestradiol concentrations in GnRH- and hCG-treated
      animals were significantly (P<0.05) higher than those in the saline-treated
      controls. LH release in response to GnRH treatment was greater (P<0.05) in ewes
      than in ewe lambs, whereas FSH release in ewes was less (P<0.05) than that of ewe
      lambs. The effects of GnRH or hCG on conceptus growth and placentation was
      determined at slaughter on Day 25. In ewes, GnRH treatment increased (P<0.05)
      luteal weight, amniotic sac width and length, and crown-rump length compared with
      controls, but had no effect on these parameters in ewe lambs. In ewes, hCG
      treatment also enhanced (P<0.05) luteal weight, amniotic sac width and length,
      crown-rump length, embryo weight and number of placentomes as compared with
      controls. In ewe lambs, there was no difference (P<0.05) between hCG and control
      groups in luteal weight, embryo weight and amniotic sac width but crown-rump
      length, amniotic sac length and the number of placentomes forming the placenta
      were greater (P<0.05). In conclusion, GnRH or hCG treatment on Day 12 of
      pregnancy can increase ovarian function, conceptus growth and placental
      attachment in ewes. However, these treatments were less effective in ewe lambs.

PMID- 17174491
TI  - Sperm DNA fragmentation in a random sample of the Spanish boar livestock.
AB  - A collection of 180 chilled boar semen samples, randomly chosen from stocks
      currently used for routine characterization of standard seminal quality, were
      studied for DNA fragmentation status using the sperm chromatin dispersion test
      and the DNA fragmentation index (DFI: percent of abnormal cell versus normal
      cells for DNA fragmentation) was determined. Values for sperm motility, acrosome
      status, coiled tails and abnormal head morphology, including presence and
      position of cytoplasmic droplets were also obtained. The DFI in the whole sample
      presented a wide range of variation with values oscillating between practically
      0% and 47.95% and do not fit to a normal distribution. The most frequent classes
      (83.3%) presented a DFI lower than a 5%. Significant correlations between sperm
      DNA fragmentation and sperm motility, acrosome status, frequency of distal
      droplets, coiled tails and abnormal head morphology, were not observed. However,
      the presence of proximal cytoplasmic droplets showed a significant correlation
      with the level of DNA fragmentation observed in the ejaculated spermatozoa.

PMID- 17174492
TI  - Characterization of physiochemical and biological properties of an insulin/lauryl
      sulfate complex formed by hydrophobic ion pairing.
AB  - An insulin/lauryl sulfate complex was prepared by hydrophobic ion pairing (HIP).
      The physiochemical and biological properties of the HIP complex were
      characterized using octanol/water partition measurement, isothermal titration
      calorimetry (ITC), ultraviolet-circular dichroism (UV-CD) and Fourier transform
      infrared spectroscopy (FTIR). Sodium dodecyl sulfate (SDS) bound to the insulin
      in a stoichiometric manner. The formed complex exhibited lipophilicity, and its
      insulin retained its native structure integrity. The in vivo bioactivity of the
      complex insulin was evaluated in rats by monitoring the plasma glucose level
      after intravenous (i.v.) injection, and the glucose level was compared with that
      for free insulin. The pharmacodynamic study result in rats showed that the
      complex insulin had in vivo bioactivity comparable to free insulin.

PMID- 17174493
TI  - Preparation of glass solutions of three poorly water soluble drugs by spray
      drying, melt extrusion and ball milling.
AB  - The aim of this study was to investigate the influence of the manufacturing
      process on the physicochemical properties of three poorly water soluble compounds
      (carbamazepine, dipyridamole, and indomethacin) when processed with a polymer
      (polyvinylpyrrolidone K30 (PVP)) at a 1:2 drug to polymer ratio. Melt extrusion,
      spray drying, and ball milling techniques were used to prepare glass solutions.
      Product homogeneity, dissolution, physical stability, and drug/polymer
      interactions were investigated. Particular attention was paid to solid phase
      analysis using XRPD, modulated temperature DSC, optical microscopy, and Raman
      microscopy and the importance of using a combination of techniques was
      demonstrated. The latter technique when applied to freshly ball milled samples
      exhibited the presence of drug and polymer rich areas, indicating that complete
      glass solution formation had not occurred. The three compounds produced products
      with differing physical stability with indomethacin proving the most physically
      stable. These differences in physical stability were attributed to hydrogen
      bonding of drug and polymer. The manufacturing technique did not influence
      physical stability, but it did affect dissolution. The dissolution of the spray
      dried material was generally poor, compared to melt extruded and ball milled
      products. This was probably due to rapid dissolution of PVP from the small
      particles of the spray-dried products.

PMID- 17174494
TI  - The effect of monomers on the formulation of polymeric nanocapsules based on
      polyureas and polyamides.
AB  - Formulation of nanocapsules based on polyureas and polyamides have been tested
      using a patented process. This method based on polycondensation reaction of two
      complementary monomers and spontaneous formation of oil in water emulsion, is an
      alternative concept to the known technique based on the same type of reaction
      used for the formulation of microcapsules, and in which the lipophilic monomer
      was emulsified in the organic phase before the formation of the polymeric
      membrane. Nanocapsules can be prepared from different monomers. Wall based on
      cross-linked polymer contributes to the stability of nanocapsules during and
      after formulation. The permeability of the polymeric wall is related to its
      crystallinity and contributes to the growth of nanocapsule membrane by the
      diffusion of the hydrophilic monomers to get stable colloidal suspensions.

PMID- 17174496
TI  - A purified extract from Clematis mandshurica prevents staurosporin-induced
      downregulation of 14-3-3 and subsequent apoptosis on rat chondrocytes.
AB  - OBJECTIVE: To dissect the mechanism of the protection of staurosporin-induced
      apoptosis on rat chondrocytes by a purified extract from Clematis mandshurica.
      DESIGN: Primary cultured rat articular chondrocytes as well as RCJ3.1C.18 cells
      were incubated with 1 microM staurosporin and 300 microg/ml purified extract from
      Clematis mandshurica. Western blot assay, silencing 14-3-3 gene and
      immunoprecipitation were conducted. RESULTS: Clematis mandshurica prevented
      staurosporin-induced downregulation of several antiapoptotic bcl-2 family
      proteins Bcl-xL and Bcl-2, and staurosporin-induced upregulation of an apoptotic
      bcl-2 family protein Bax. Clematis mandshurica also prevented staurosporin
      induced downregulation of a premitochondrial antiapoptotic protein 14-3-3. It is
      noticeable that siRNA to 14-3-3 abolished the prevention of caspase-3 activation
      by Clematis mandshurica. Furthermore viability assay corroborated that silencing
      of 14-3-3 gene abolished this apoptosis protection efficacy by Clematis
      mandshurica. Immunoprecipitation assay elucidated that Clematis mandshurica
      prevented the staurosporin-induced reduction of the interactions between 14-3-3
      with phospho-ser112-Bad and Bcl-xL to phospho-ser155-Bad. CONCLUSIONS: Clematis
      mandshurica prevents staurosporin-induced apoptosis of rat chondrocytes via 14-3
      3.

PMID- 17174495
TI  - Polymer: bioceramic composites optimization by tetracycline addition.
AB  - The aim of this study was to evaluate the biocompatibility of composites of poly
      lactic acid polymer (PLA) and copolymer of lactic and glycolic acid (PLGA),
      dispersed in a bioceramic matrix, Osteosynt (BC), to which tetracycline (TC) was
      added. The in vitro test used direct contact test (ASTM F-813) and elution test
      (USP-XXIII, ISO 10993-5), and in vivo evaluation was performed after subcutaneous
      implantation in outbread Swiss mice. The 0.01% (w/w) TC addition did not affect
      composite cytotoxicity in vitro. The macroscopic and histologic evaluation in
      vivo after 1, 7, 13, 21, 28 and 56 days showed an initial intense infiltrate of
      inflammatory cells for most of the groups. The tissue showed normal pattern after
      21 days for all the groups. TC addition exhibited significantly larger reduction
      of inflammation signs (Mann-Whitney test, p<0.05) in the critical period of the
      resolution of the inflammatory process. Angiogenesis, cellular adsorption and
      fibrous deposit were observed on SEM evaluation. In conclusion, TC addition
      optimized composites polymer/bioceramic biocompatibility, contributing to anti
      inflammatory response during the early phases of the wound healing process.

PMID- 17174497
TI  - Development of a harmonised method for the profiling of amphetamines: III.
      Development of the gas chromatographic method.
AB  - This study focused on gas chromatographic analysis of target compounds found in
      illicit amphetamine synthesised by the Leuckart reaction, reductive amination of
      benzyl methyl ketone, and the nitrostyrene route. The analytical method was
      investigated and optimised with respect to introduction of amphetamine samples
      into the gas chromatograph and separation and detection of the target substances.
      Sample introduction using split and splitless injection was tested at different
      injector temperatures, and their ability to transfer the target compounds to the
      GC column was evaluated using cold on column injection as a reference. Taking the
      results from both techniques into consideration a temperature of 250 degrees C
      was considered to be the best compromise. The most efficient separation was
      achieved with a DB-35MS capillary column (35% diphenyl 65% dimethyl silicone; 30
      m x 0.25 mm, d(f) 0.25 microm) and an oven temperature program that started at 90
      degrees C (1 min) and was increased by 8 degrees C/min to 300 degrees C (10 min).
      Reproducibility, repeatability, linearity, and limits of determination for the
      flame ionisation detector (FID), nitrogen phosphorous detector (NPD), and mass
      spectrometry (MS) in scan mode and selected ion monitoring (SIM) mode were
      evaluated. In addition, selectivity was studied applying FID and MS in both scan
      and SIM mode. It was found that reproducibility, repeatability, and limits of
      determination were similar for FID, NPD, and MS in scan mode. Moreover, the
      linearity was better when applying FID or NPD whereas the selectivity was better
      when utilising the MS. Finally, the introduction of target compounds to the GC
      column when applying injection volumes of 0.2 microl, 1 microl, 2 microl, and 4
      microl with splitless injection respectively 1 microl with split injection (split
      ratio, 1:40) were compared. It was demonstrated that splitless injections of 1
      microl, 2 microl, and 4 microl could be employed in the developed method, while
      split injection and splitless injections of 0.2 microl should be avoided.

PMID- 17174498
TI  - A case of Kabuki syndrome presenting West syndrome.
AB  - A 6-month-old girl visited our hospital because of mental retardation,
      regression, and tonic spasms in cluster. We diagnosed her as West syndrome
      because of hypsarrhythmia on electroencephalogram (EEG) and tonic spasms in
      cluster. We also diagnosed her as Kabuki syndrome because of multiple
      malformations, especially a characteristic peculiar face (resembling a Kabuki
      actor). She was first administered clonazepam, but this was not effective. Later,
      she was administered vitamin B6, valproic acid, and zonisamide. Zonisamide was
      effective, and her tonic spasms were suppressed. Her EEG at 9 months of age
      showed the disappearance of hypsarrhythmia and sporadic spike and wave complexes
      on P3, P4, O1, and O2. At 2 years of age, she still showed mental retardation,
      despite the good control of West syndrome. To the best of our knowledge, Kabuki
      syndrome presenting West syndrome has been reported in only one previous case. We
      must pay attention to the occurrence of West syndrome in Kabuki syndrome.

PMID- 17174499
TI  - Quantitative proton MRS of cerebral metabolites in laminin alpha2 chain
      deficiency.
AB  - Congenital muscular dystrophy (CMD) due to merosin (laminin alpha2 chain)
      deficiency is an autosomal recessively inherited disorder characterized by severe
      muscular weakness and hypotonia from birth on. Brain involvement is the rule and
      characterized by variable T2 hyperintensities of white matter which appears
      swollen on cranial MRI. The pathophysiology of these white matter changes is not
      clear. In five patients with laminin alpha2 deficient CMD we performed short-echo
      time localized proton MRS with determination of absolute metabolite
      concentrations in grey and white matter. In affected white matter, a consistent
      pattern of metabolites was detected comprising reduced concentrations of N
      acetylaspartate and N-acetylaspartylglutamate, creatine, and phosphocreatine, and
      to a milder degree of choline-containing compounds. In contrast, concentrations
      of myo-inositol were in the normal range. Spectra of cortical and subcortical
      grey matter were normal. The observed metabolite profile is consistent with white
      matter edema, that is reduced cellular density, and relative astrocytosis. This
      interpretation is in line with the hypothesis that laminin alpha2 deficiency
      results in leakage of fluids across the blood-brain barrier and a
      histopathological report of astrocytic proliferation in CMD.

PMID- 17174500
TI  - Effect of high-dose methyl-prednisolone on brainstem encephalopathy and basal
      ganglia impairment complicating cat scratch disease.
AB  - Cat scratch disease (CSD) is a zoonotic illness caused by the Gram negative
      bacillus Bartonella henselae characterized by a small skin lesion at the site of
      a bite, lick or scratch by a cat, commonly followed by regional lymphadenopathy 1
      or 2 weeks later. We report herein on severe neurological complications of CSD
      combining brainstem encephalopathy and basal ganglia impairment. This 12-year-old
      female acutely presented to a local hospital with profound coma and a prolonged
      tonic posturing of extremities. On the neurological examination she was deeply
      comatose with pin-point pupils and lack of vestibulo-ocular responses, suggestive
      of brainstem encephalopathy, along with marked rigid hypertonicity suggestive
      also of basal ganglia impairment. Initially suspecting Herpes simplex
      encephalitis or acute disseminated encephalomyelitis she was promptly started
      with high-dose methyl-prednisolone and acyclovir. Her parents apparently reported
      that she was scratched by a kitten some 4 weeks prior to her present admission
      and as such, suspecting CSD, she was begun with doxycycline and rifampicin. Her
      serology had proven positive for IgM antibodies to Bartonella henselae
      establishing the diagnosis. She regained consciousness after 4 days and the signs
      of brainstem and extra-pyramidal impairment also gradually abated and disappeared
      after 10 days. A follow-up exam after a month disclosed mild extra-pyramidal
      abnormalities which disappeared after 3 months. Although extremely rare, CSD
      should be also considered in a patient presenting with a severe encephalopathy
      and associated basal ganglia impairment. The prompt administration of high-dose
      methyl-prednisolone upon admission may have contributed to the favorable outcome
      in our patient and therefore should be advocated in any patient presenting with
      profound encephalopathy regardless the underlying etiology recovered later.

PMID- 17174501
TI  - Cerebral involvement in respiratory syncytial virus disease.

PMID- 17174502
TI  - Accelerating the transit time of barium sulphate suspensions in small bowel
      examinations.
AB  - PURPOSE: To determine whether hyperosmolar and effervescent agents proven
      individually to accelerate transit time in the barium small bowel examination
      have an additive effect when combined, surpassing that of either agent alone.
      MATERIALS AND METHODS: One hundred and forty-nine patients were randomised to
      four groups. Three hundred milliliters of barium sulphate alone was given to the
      first group. Fifteen milliliters of iodinated hyperosmolar contrast agent
      (Gastrografin, meglumine/sodium diatrizoate, Schering) was given in addition to
      barium sulphate to the second group while six packets of effervescent granules
      (Carbex, Ferring) were added for the third group. The final group was given a
      combination of both additives and barium sulphate. The time taken following
      ingestion for the contrast column to reach the caecum, as assessed by frequent
      interval fluoroscopy, was recorded. A subgroup of 32 patients were selected
      randomly from the four groups, 8 from each and assessed for quality of
      examination. Statistical assessments were made using Kruskal-Wallis and Mann
      Whitney tests. RESULTS: One hundred and nineteen patients were analysed after
      exclusions. The addition of accelerant to barium sulphate, both individually and
      in combination significantly reduced the small bowel transit time (p<0.001). No
      significant difference existed between the additives when used with barium alone.
      The combined group had significantly faster transit times compared to the
      hyperosmolar group (p=0.02). Differences between combined and effervescent groups
      tended towards significance (p=0.09). No significant difference existed between
      groups when examination quality was assessed. CONCLUSION: These results suggest
      that the addition of combined effervescent and hyperosmolar agents to the barium
      suspension may significantly shorten the small bowel transit time without
      adversely affecting examination quality. This has implications for patient
      acceptability of the examination as well as potentially reducing screening time
      and therefore radiation dose.

PMID- 17174503
TI  - Liver manifestations of cystic fibrosis.
AB  - Chronic liver disease is one of the major complications of cystic fibrosis (CF).
      Significant liver disease is seen in 13-25% of children with CF. Improved life
      expectancy and prolonged follow-up have favored better characterization of the
      hepatic manifestations of CF and allowed direct observation of an increasing
      number of liver-related events. Liver disease typically develops in the first
      decade of life, with the incidence dropping rapidly after the age of 10 years.
      The wide spectrum of liver disease ranging from asymptomatic gallbladder
      abnormalities to biliary cirrhosis will be reviewed in this article.

PMID- 17174505
TI  - Identification and biodegradation potential of a novel strain of Dietzia cinnamea
      isolated from a petroleum-contaminated tropical soil.
AB  - A bacterial strain, named P4, isolated previously from microcosms containing oil
      contaminated soil collected from an environmentally protected area of a tropical
      Atlantic forest (Biological Reserve of Poco das Antas) located in Brazil was
      identified as Dietzia cinnamea by morphological, biochemical and genotypic tests.
      Arabian Light and Marlin oils were both degraded when strain P4 was tested for
      oil degradation ability in microplates. Total Petroleum Hydrocarbons (TPH)
      analysis, determined by gas chromatography, showed that strain P4 degraded a wide
      range of n-alkanes, and also pristane and phytane. Furthermore, this strain was
      also able to grow in mineral liquid media amended with carbazole, quinoline,
      naphthalene, toluene, gasoline and diesel as the sole carbon sources. The species
      D. cinnamea has been previously described with only one representative strain
      isolated from a perianal swab of a patient with a bone marrow transplant. With
      the results presented here this species is implicated not only as a human
      pathogen but also as a potential strain for further studies concerning its role
      for bioremediation of oil contaminated soil.

PMID- 17174506
TI  - Determination of five components in Ixeris sonchifolia by high performance liquid
      chromatography.
AB  - A high performance liquid chromatography (HPLC) method was developed for the
      simultaneous quantification of five major active ingredients (markers) in Ixeris
      sonchifolia (Bge.) Hance, namely chlorogenic acid, caffeic acid, luteolin-7-O
      beta-D-glucuronide, luteolin-7-O-beta-D-glucoside and luteolin. Samples were
      extracted with 70% methanol. The chromatographic separation was performed on a
      Hypersil ODS(2) column (250 mm x 4.6 mm i.d.; 5 microm) with a gradient of
      acetonitrile and 0.5% (v/v) aqueous acetic acid, at a flow rate of 1.0 ml/min,
      detected at 335 nm. Five regression equations showed good linear relationships
      (r(2)>0.999) between the peak area of each marker and concentration. The assay
      was reproducible with overall intra- and inter-day variation of less than 3.2%.
      The recoveries, measured at three concentration levels, varied from 94.1% to
      100.7%. This assay was successfully applied to the determination of the 5
      bioactive compounds in 18 samples. The results indicated that the developed assay
      method was rapid, accurate, reliable and could be readily utilized as a quality
      control method for I. sonchifolia (Bge.) Hance.

PMID- 17174507
TI  - Isolation, structural elucidation and characterization of impurities in Cefdinir.
AB  - Three unknown impurities in Cefdinir bulk drug at levels below 0.2% (ranging from
      0.05 to 0.2%) have been detected by high performance liquid chromatography
      (HPLC). These impurities were isolated from crude sample of Cefdinir using
      preparative HPLC. Based on the spectral data (NMR, IR and MS) the structures of
      these impurities were characterized as (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2
      hydroxyiminoacetamido]-8-oxo-3-vinyl-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2
      carboxylic acid-5-oxide (I). (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2
      hydroxyiminoacetamido]-8-oxo-3-vinyl-5-thia-1-azabi-cyclo [4.2.0] oct-3-ene-2
      carboxylic acid (II). (6R, 7R)-7-[(z)-2-(2-aminothiazol-4-yl)-2
      hydroxyiminoacetamido]-8-oxo-3-methyl-5-thia-1-azabicyclo-[4.2.0]oct-2-ene-2
      carboxylic acid (III), respectively. The origin and structural elucidation of all
      impurities have been discussed.

PMID- 17174508
TI  - Determination of clarithromycin in human plasma by liquid chromatography
      electrospray ionization tandem mass spectrometry.
AB  - A rapid and sensitive method has been developed for the determination of
      clarithromycin in human plasma with liquid chromatography-tandem mass
      spectrometry. Clarithromycin and the internal standard, telmisartan were
      precipitated from the matrix (50 microl) with 200 microl acetonitrile and
      separated by HPLC using formic acid:10 mM ammonium acetate:methanol (1:99:400,
      v/v/v) as the mobile phase. The assay based on detection by electrospray positive
      ionization mass spectrometry in the multiple-reaction monitoring mode was
      finished within 2.4 min. Linearity was over the concentration range 10-5000 ng/ml
      with a limit of detection of 0.50 ng/ml. Intra- and inter-day precision measured
      as relative standard deviation were <3.73% and <9.93%, respectively. The method
      was applied in a bioequivalence study of two tablet formulations of
      clarithromycin.

PMID- 17174509
TI  - Identification of tanshinones and their metabolites in rat bile after oral
      administration of TTE-50, a standardized extract of Salvia miltiorrhiza by HPLC
      ESI-DAD-MSn.
AB  - TTE-50 is a standardized extract of Salvia miltiorrhiza which mainly consisted of
      tanshinones. A sensitive and specific method using liquid chromatography-diode
      array detection-electrospray ionization (ESI) ion trap mass spectrometry was
      established for the study of the constituents and metabolites of TTE-50 in rat
      bile sample after oral administration. The bile samples were extracted with ethyl
      acetate (EtOAc) of three-fold volume for three times. The chromatographic
      separation was carried out on a Zorbax Extend-C18 column with a gradient elution
      program whereas acetonitrile-water was used as mobile phase. Mass spectra were
      acquired in positive ionization mode and data-dependant scan was used for the
      identification of the tanshinones and metabolites in the bile samples.
      Identification and structural elucidation of the tanshinones and their
      metabolites in bile samples were performed by comparing their retention-times and
      full scan MS(n) spectra with those of reference compounds and data in the
      literatures. Sixteen tanshinones in TTE-50 along with seventeen phase I
      metabolites were identified simultaneously. The metabolic modification could take
      place in the C-4 side chain of tanshinone IIA, from methyl to primary alcohol,
      then to aldehyde group was proposed for the first time. The established method
      was valuable for the study of the metabolism of complex system such as herbal
      extracts or traditional Chinese medicine (TCM) formula.

PMID- 17174511
TI  - Factors influencing operation time of laparoscopy-assisted distal subtotal
      gastrectomy: analysis of consecutive 100 initial cases.
AB  - AIMS: There is little information on patient selection criteria for laparoscopy
      assisted distal gastrectomy (LADG) that would facilitate a successful initial
      experience for a surgeon new to the procedure. This study aimed to establish
      patient selection criteria that will allow increased proficiency and shorter
      operation times for the LADG procedure. METHOD: One hundred LADG with
      lymphadenectomy and no other combined procedures were consecutively performed by
      one surgeon. These 100 consecutive LADG procedures were analyzed retrospectively
      from a prospectively designed computer database. Uni- and multivariate analyses
      were performed to identify factors influencing operation time. RESULTS: According
      to univariate analysis, operation time was influenced by sex, BMI, surgical
      experience, and tumor location, whereas multivariate analysis indicated that
      operation time was significantly influenced only by BMI and surgical experience.
      The same analyses of only the first 50 cases showed that sex, BMI, surgical
      experience, and tumor location were independently associated with operation time.
      As BMI increased, so did operation time, whereas operation time decreased with
      increasing surgical experience. CONCLUSION: This study suggests that surgeons who
      have limited experience with this advanced procedure may shorten operation time
      by considering patient and tumor characteristics in their early attempts at LADG.
      With a shortened operation time, surgeon with limited experience may become
      proficient to LADG rapidly.

PMID- 17174510
TI  - Use of boronic acid disk methods to detect the combined expression of plasmid
      mediated AmpC beta-lactamases and extended-spectrum beta-lactamases in clinical
      isolates of Klebsiella spp., Salmonella spp., and Proteus mirabilis.
AB  - A study using boronic acid (BA), an AmpC enzyme inhibitor, was designed to detect
      the combined expression of plasmid-mediated AmpC beta-lactamases (pAmpCs) and
      extended-spectrum beta-lactamases (ESBLs) in bacterial isolates naturally lacking
      chromosomal ampC genes. A total of 122 Klebsiella spp., Salmonella spp., and
      Proteus mirabilis isolates producing or nonproducing pAmpCs and/or ESBLs were
      analyzed. Detection of genes encoding ESBLs and AmpCs was confirmed by polymerase
      chain reaction (PCR) followed by sequencing of PCR products. A > or = 5-mm
      increase in zone diameter for i) cefoxitin (FOX) and/or cefotetan (CTT)
      containing BA versus FOX and/or CTT alone was considered positive for AmpC; ii)
      ceftazidime (CAZ)-clavulanate (CA) and/or cefotaxime (CTX)-CA tested in
      combination with BA versus CAZ and/or CTX containing BA was considered positive
      for ESBL. The disk tests of FOX and/or CTT alone and with BA detected 98.4% of
      organisms producing pAmpCs. All of the 21 pAmpC and ESBL coproducers were
      accurately detected ESBL by the disk tests of CTX-CA and/or CAZ-CA containing BA
      and CTX and/or CAZ containing BA. In conclusion, The BA disk test using Clinical
      and Laboratory Standards Institute methodology is simple and very efficient
      method to detect pAmpC and ESBL in organisms naturally lacking chromosomal AmpC
      enzymes. In particular, the method accurately detects the isolates that harbor
      both AmpCs and ESBLs.

PMID- 17174512
TI  - Intrapericardial isolation of the inferior vena cava through a transdiaphragmatic
      pericardial window for tumor resection without sternotomy or thoracotomy.
AB  - AIMS: The prognosis for patients with advanced tumors invading the inferior vena
      cava (IVC) is dismal and surgical treatments for these tumors are challenging. A
      surgical approach that avoids sternotomy and thoracotomy for tumors invading the
      IVC even to the level of the hepatocaval junction would be extremely helpful.
      METHODS: The intrapericardial IVC was isolated via a transdiaphragmatic
      pericardial window using a transabdominal approach. Hepatectomy was then applied
      via an anterior approach until the IVC was seen. Total hepatic vascular exclusion
      was achieved by clamping the portal triad, intrapericardial IVC and infrahepatic
      IVC. We removed the primary tumor, the liver portion involved and the tumor
      thrombi, with segmental resection of the IVC. Vascular continuity was
      reestablished using a 20-mm-diameter polytetrafluoroethylene graft. RESULTS: Four
      patients with tumors invading the IVC were treated with this method. All
      underwent gross en-bloc tumor resections and all survived. CONCLUSION: This
      method for the resection of IVC tumors could avoid emboli dislodging from the
      tumor thrombi, prevent the complications of sternotomy, cardiopulmonary bypass
      and shorten operative times.

PMID- 17174513
TI  - Determination of sentinel lymph node (SLN) status in primary breast cancer by
      prospective use of immunohistochemistry increases the rate of micrometastases and
      isolated tumour cells: analysis of 174 patients after SLN biopsy.
AB  - AIM: The objective of the present study was to evaluate the prospective use of
      immunohistochemistry (IHC) for histopathological diagnosis of sentinel lymph
      node(s) (SLN) in primary breast cancer using stage migration and non-SLN
      metastases as endpoints in relation to metastatic involvement. METHOD: Serial
      sectioning and prospective use of IHC were applied to SLN examination in addition
      to routine haematoxylin-eosin staining in 174 consecutive patients with unifocal
      T1-T2 breast cancer included in a National Sentinel Node Study. Axillary lymph
      node dissection (ALND) was performed in all cases with macrometastases,
      micrometastases and isolated tumour cells (ITC). RESULTS: The SLN was found in
      173/174 patients and a metastatic foci was found in 50 patients including 28/50
      with macrometastases, 16/50 with micrometastases and 6/50 with ITC. IHC detected
      3/16 of the micrometastases and 4/6 of ITC. Stage migration from N0 to N1mi was
      encountered in 3/132 patients by use of IHC. Non-SLN metastases were noted in
      15/28 of patients with macrometastases and in 3/16 of patients with
      micrometastases, whereas no patient with ITC had additional metastases (p=0.007).
      CONCLUSION: The prospective use of IHC and serial sectioning for
      histopathological diagnosis of SLNs increased the detection rate of N1mi and ITC,
      but only 3/132 patients were stage-migrated by use of IHC. Patients with ITC did
      not have any risk of non-SLN metastases, supporting that ALND can safely be
      omitted in this group of patients.

PMID- 17174514
TI  - Doxorubicin levels in the serum and ascites of patients with ovarian cancer.
AB  - AIMS: To investigate the diffusion and accumulation of doxorubicin metabolites in
      the ascites of patients with ovarian cancer following intravenous injection, as a
      model for intraperitoneal accumulation of drugs. METHODS: The concentrations of
      doxorubicin and its metabolites [Doxorubicinol (Dox-ol), 7-deoxydoxorubicinolone
      (7d-Dox-ol-on) and 7-deoxydoxorubicinone (7d-Dox-on)] were measured using high
      performance liquid chromatography in the serum and in the ascites of seven
      patients with recurrent ovarian carcinoma suffering from symptomatic ascites and
      treated with intravenous doxorubicin. RESULTS: Doxorubicin metabolites
      accumulated in the peritoneal cavity. The concentrations of the doxorubicin
      metabolites were initially higher in the serum compared to the ascitic fluid, but
      following several hours the doxorubicin metabolites became higher in the ascites,
      and remained detectable in the ascites for up to 168h, long after disappearance
      from the serum. CONCLUSIONS: Doxorubicin metabolites accumulate in the ascites
      and are cleared more slowly from the peritoneal compartment than from the serum.
      Accumulation in the peritoneal cavity with prolonged half-life should be
      considered when administering medication in patients with ascites.

PMID- 17174515
TI  - Soft tissue sarcomas of the popliteal fossa: outcome and risk factors.
AB  - BACKGROUND: Limb salvage surgery of popliteal soft tissue sarcomas may be
      hampered due to the incomplete anatomical containment of this region and the
      vicinity of neurovascular structures. The scope of this study was to determine
      outcome and to define risk factors. PATIENTS AND METHODS: 27 patients (53.3+/
      15.8 y; 16/27 male) with popliteal soft tissue sarcomas were assessed. Mean
      follow-up was 40.9+/-33.8 months (48.5+/-36.7 months in surviving patients). 9/27
      patients were included after prior treatment elsewhere (5 after intralesional
      resections and 4 local recurrences). The lesions were staged IB in 8/27 patients,
      IIB in 17/27 and III in 2/27. Immediate amputations were performed in 7/27
      patients. 15/27 patients were subjected to radiation therapy (preoperative in
      6/15 cases), 8/27 patients received chemotherapy (5/8 preoperatively). RESULTS:
      Overall survival and disease-free survival at 5 y was 63.0% and 59.5%. Local
      recurrence occurred in 2 patients. 8/27 patients developed metastatic disease
      after 28.9+/-9.8 months. Survival (p=0.397) and disease-free survival (p=0.113)
      did not differ in patients after amputations vs limb salvage. Application of
      radiation therapy was associated with a better survival (p=0.003). Complications
      related to the surgical intervention were recorded in 2/27 patients,
      complications related to radiation therapy occurred in 6/15 patients. DISCUSSION:
      Despite being extra-compartmental, popliteal sarcomas can be treated with a high
      rate of limb salvage while equal safety compared to amputations is maintained.
      Irradiation improved survival in our patient population. In cases with
      involvement of neurovascular structures, preoperative down-staging with radio or
      chemo-therapy may prevent amputation.

PMID- 17174516
TI  - Carcinoembryonic antigen (CEA) measurement during follow-up for rectal carcinoma
      is useful even if normal levels exist before surgery. A retrospective study of
      CEA values in the TME trial.
AB  - BACKGROUND: Carcinoembryonic antigen (CEA) as a marker in the follow-up after
      curative resection of colorectal carcinoma (CRC) is often omitted from follow-up
      despite guideline recommendations. One reason is the assumption that when a
      normal CEA value exists before curative resection of CRC, it will neither rise
      during follow-up. This study investigates this relationship. METHOD: Data were
      derived from a study initiated to evaluate treatment regimes for rectal carcinoma
      (Dutch TME trial, n=1861) from which 954 were eligible for analysis. Recurrent
      disease occurred in 272 of these patients (29.5%). The pre-operative CEA value
      was compared to CEA values during follow-up, using threshold values of 2.5 and
      5.0 ng/ml. RESULTS: Normal pre-operative CEA values were present in 63% (CEA<5.0)
      and 39% (CEA<2.5) of patients with recurrent disease. Patients with a normal pre
      operative CEA and recurrent disease had elevated CEA values during follow-up in
      41% (CEA<5.0), 50% (CEA<2.5) and in 60% with both threshold values when the last
      measurement was done within 3 months before recurrent disease was diagnosed.
      CONCLUSION: A normal pre-operative CEA is common in patients with rectal
      carcinoma. CEA does rise due to recurrent disease in at least 50% of patients
      with normal pre-operative values. Serial post-operative CEA testing cannot be
      discarded based on a normal pre-operative serum CEA.

PMID- 17174517
TI  - Prognostic factors and outcome in women with uterine sarcoma.
AB  - OBJECTIVES: A retrospective analysis of patients with uterine sarcoma was
      undertaken to assess prognostic factors and treatment related outcomes. PATIENTS
      AND METHODS: Ninety-four patients (median age: 60years, range: 20-93years) with a
      histologically verified uterine sarcoma treated at the McGill University Health
      Centre (MUHC) between 1989 and 2004 were identified from the tumor registry and
      pathology database. RESULTS: Twenty-eight patients had an endometrial stromal
      sarcoma (ESS), 30 had a leiomyosarcoma (LMS), and 36 had mixed muellerian tumors
      (MMT). According to FIGO classification, Stage I, II, III, and IV tumors were
      identified in 49, 7, 20, and 18 patients, respectively. At the time of analysis,
      55.5% of patients (52/94) were dead due to progressive sarcoma disease; 8.5% of
      the patients (8/94) were alive with disease recurrence, and 36.2% (34/94) were
      alive without disease recurrence, with a median survival of 35months. Univariate
      analysis demonstrated a statistically significant association between overall
      survival and histology in favor of patients with ESS (p<0.001). Analyzing each of
      the histological subtypes separately, adjuvant treatment with chemotherapy and/or
      hormonal treatment had no demonstrable impact on overall survival. In
      multivariate analysis age and advanced stage, remained a significant predictor
      for overall survival in patients with LMS and MMT, but not in patients with ESS.
      Regarding adjuvant treatment, radiotherapy had a significant impact on overall
      survival only in patients with MMT (p=0.002). CONCLUSIONS: In patients with
      uterine sarcoma, in comparison to LMS and MMT, ESS tends to present as a less
      aggressive disease with a favorable outcome. Furthermore, reflected by an
      improved overall survival after radiotherapy only in patients with MMT, it seems
      to be mandatory to differentiate between these histological subtypes.

PMID- 17174519
TI  - Sudden deflation of a tourniquet caused by lowering of the operating table.

PMID- 17174518
TI  - [Perioperative analgesia with continuous peripheral nerve blocks in children].
AB  - Recently, regional anaesthesia in children has generated increasing interest. But
      single injection techniques have a limited duration of postoperative analgesia.
      Then, continuous peripheral nerve blocks have taken an important position in the
      anaesthetic arsenal, allowing an effective, safe and prolonged postoperative pain
      management. As adults, indications for continuous peripheral nerve blocks depend
      on the analysis of individual benefits/risks ratio. Main indications are intense
      postoperative pain surgical procedures, with or without postoperative
      rehabilitation, and complex regional pain syndrome. Contraindications to these
      procedures are rather similar to those in adults, plus parental and/or children
      refusal. Continuous peripheral nerve blocks are usually performed under general
      anaesthesia or sedation in children, and require appropriate equipment in order
      to decrease the risk of nerve injury. New techniques, such as transcutaneous
      nerve stimulation or ultrasound guidance, appeared to facilitate nerve and plexus
      approach identification in paediatric patients. Nevertheless, continuous
      peripheral nerve block may theoretically mask a compartment syndrome after trauma
      surgical procedures. Finally, ropivacaine appears to be the most appropriate drug
      for continuous peripheral nerve blocks in children, requiring low flow rates and
      concentrations of local anaesthetic. These techniques may facilitate early
      ambulation by an improved pain management or even postoperative analgesia at home
      with disposable pumps. One might infer from the current review that excellent
      pain relief coupled with a reduction of side effects would contribute to improve
      the quality of life and to decrease the frequency of disabling behavioural
      modifications in children, sometimes psychologically injured by hospital stay and
      postoperative pain.

PMID- 17174520
TI  - [Colonic necrosis following a pancreatic pseudocyst embolization].
AB  - A 43-year-old man with chronic alcohol pancreatitis was admitted in our intensive
      care unit for an haemorrhagic shock. An abdominal CT-scan performed on admission
      showed bleeding from a vessel in a pancreatic pseudocyst. Initial treatment
      included intravenous fluids, transfusion, mechanical ventilation and vasopressive
      support. Percutaneous arterial embolization (PAE) of a bleeding right superior
      colon artery was performed with an initial good result. Nevertheless after
      initial clinical improvement, hypotension refractory to fluid management
      occurred. An abdominal CT-scan disclosed pneumatosis in right colon. A right
      hemicolectomy was performed. Histologic analysis confirmed ischemic colitis. The
      patient recovered and was discharged from the intensive care unit. Colitis
      necrosis after PAE for pancreatic pseudoaneurysm had never been described before.
      It should be suspected when haemodynamic instability occurs following PAE.

PMID- 17174521
TI  - Multiple seropathotypes of verotoxin-producing Escherichia coli (VTEC) disrupt
      interferon-gamma-induced tyrosine phosphorylation of signal transducer and
      activator of transcription (Stat)-1.
AB  - Verotoxin-producing Escherichia coli (VTEC) O157:H7 inhibits interferon-gamma
      stimulated tyrosine phosphorylation of signal transducer and activator of
      transcription (Stat)-1 in epithelial cells, independent of Verotoxins and the
      locus of enterocyte effacement pathogenicity island. Although E. coli O157:H7 is
      the major cause of disease in humans, non-O157:H7 VTEC also cause human disease.
      However, the virulence properties of non-O157:H7 VTEC are less well
      characterized. The aims of this study were to define the ability of VTEC strains
      of differing seropathotypes (classified as A-E) to inhibit interferon-gamma
      stimulated Stat1-phosphorylation and to further characterize the bacterial
      derived inhibitory factor. Confluent T84 and HEp-2 cells were infected with VTEC
      strains (MOI 100:1, 6h, 37 degrees C), and then stimulated with interferon-gamma
      (50 ng/mL) for 0.5h at 37 degrees C. Whole-cell protein extracts of infected
      cells were collected and prepared for immunoblotting to detect tyrosine
      phosphorylation of Stat1. The effects of E. coli O55 strains, the evolutionary
      precursors of VTEC, on Stat1-tyrosine phosphorylation were also determined. The
      effects of isogenic mutants of O-islands 47 and 122 were tested to determine the
      role of genes encoded on these putative pathogenicity islands in mediating VTEC
      inhibition of the interferon-gamma-Stat1 signaling cascade. To evaluate potential
      mechanism(s) of inhibition, VTEC O157:H7-infected cells were treated with
      pharmacological inhibitors, including, wortmannin and LY294002. Relative to
      uninfected cells, Stat1-tyrosine phosphorylation was significantly reduced after
      6h infection of both T84 and HEp-2 cells by VTEC strains of all five
      seropathotypes. E. coli O55 strains, but not enteropathogenic E. coli (EPEC),
      also caused inhibition of Stat1-tyrosine phosphorylation, suggesting that this
      effect was acquired early in the evolution of VTEC. Stat1-activation did not
      recover in epithelial cells infected with isogenic mutants of O-islands 47 and
      122, indicating that the inhibitory factor was not contained in these genomic
      regions. Stat1-phosphorylation remained intact when VTEC-infected cells were
      treated with wortmannin (0-100 nM), but not by treatment with the more specific
      PI3-kinase inhibitor, LY294002. Inhibition of interferon-gamma stimulated Stat1
      tyrosine phosphorylation by VTEC of multiple seropathotypes indicates the
      presence of a common inhibitory factor that is independent of bacterial virulence
      in humans. The results of treatment with wortmannin suggest that the bacterial
      derived inhibitory factor employs host cell signal transduction to mediate
      inhibition of Stat1-activation.

PMID- 17174522
TI  - Baseline cognitive function predicts rate of decline in basic-care abilities of
      individuals with dementia of the Alzheimer's type.
AB  - Decline in basic self-care abilities is an important risk factor for
      institutionalization in individuals with dementia. The ability to predict such
      decline would be of clinical importance in working with families of dementia
      patients. Research has suggested that cognitive decline may precede loss of
      functional capacity. This paper utilized a large sample of probable Alzheimer's
      disease patients (N=150) who were evaluated longitudinally to assess the pattern
      of neuropsychological functioning predictive of rapid decline in self-care. The
      findings indicated that despite initial equality of Lawton Physical Self
      Maintenance (PSM) scores, patients showing rapid decline of PSM function
      displayed significantly more impaired performance on neuropsychological measures
      at diagnosis. They also exhibited a statistically significant difference in the
      pattern of scores from patients who remained stable. The pattern of the rapid
      declining group included more severe impairment in visual spatial skills,
      processing speed, and concept formation. Difficulties in using individual
      patients' cognitive profiles to make predictions about future rate of PSM decline
      are discussed.

PMID- 17174523
TI  - The frataxin-encoding operon of Caenorhabditis elegans shows complex structure
      and regulation.
AB  - The genome of the nematode Caenorhabditis elegans is unusual among eukaryotes, in
      that it contains operons. Approximately 15% of genes in the worm are clustered
      into groups of between two and eight genes, which are under the control of shared
      regulatory sequences. Polycistronic transcripts from such operons are trans
      spliced, during transcription, to produce mature monocistronic messengers. The C.
      elegans frataxin gene, frh-1, is encoded in the operon CEOP2232. This is one of
      the largest operons identified thus far in the C. elegans genome. Here we
      describe in detail the structure of all of the coding units within this operon.
      The operon is composed of eight genes of a diverse nature, organized in a complex
      structure. We have produced transgenic strains carrying fusions between gfp and a
      number of genes from the operon. These constructs show complex differential
      expression patterns that suggest the presence of internal promoters and
      regulatory sequences in the operon. This organization would permit both
      coordinated expression and differential expression of the components of the
      CEOP2232 operon. The heterogeneity of the genes, and their complex expression
      patterns, suggests that the clustering of CEOP2232 is not due to a need for
      synchronized expression of genes involved in the same physiological pathway.

PMID- 17174524
TI  - Endocrinology: the active partner in PNI research.
AB  - For the past two decades, research appearing in the pages of Brain, Behavior, and
      Immunity (BBI), as well as other journals, has significantly deepened our
      understanding of the complexities of endocrine regulation of immunity in states
      of health and disease. This mini-review discusses contributions that
      endocrinology has made to the field of psycho-neuroimmunology (PNI), as well as
      discoveries that PNI researchers have made of the pervasive interactions between
      the endocrine and immune systems. We highlight the endocrine-immune interface,
      emphasizing similarities between the immune and endocrine systems as well as
      hormone/cytokine interactions. Differing endocrine-immune responses to acute and
      chronic psychosocial stress have been clarified during this time frame with the
      use of novel stress and endocrine sampling paradigms. Furthermore, investigations
      examining the role of cytokine involvement in acquired glucocorticoid resistance
      in illnesses like depression have expanded our understanding of the complexity of
      the endocrine-immune response to psychosocial stress. We have selected
      literature, with a focus on human studies, to illustrate these principals. We
      conclude with a discussion of the clinical relevance of endocrine-immune
      investigations and thoughts about the next decade of endocrine research in PNI.

PMID- 17174525
TI  - Role of the CX3CR1/p38 MAPK pathway in spinal microglia for the development of
      neuropathic pain following nerve injury-induced cleavage of fractalkine.
AB  - Accumulating evidence suggests that microglial cells in the spinal cord play an
      important role in the development of neuropathic pain. However, it remains
      largely unknown how glia interact with neurons in the spinal cord after
      peripheral nerve injury. Recent studies suggest that the chemokine fractalkine
      may mediate neural/microglial interaction via its sole receptor CX3CR1. We have
      examined how fractalkine activates microglia in a neuropathic pain condition
      produced by spinal nerve ligation (SNL). SNL induced an upregulation of CX3CR1 in
      spinal microglia that began on day 1, peaked on day 3, and maintained on day 10.
      Intrathecal injection of a neutralizing antibody against CX3CR1 suppressed not
      only mechanical allodynia but also the activation of p38 MAPK in spinal microglia
      following SNL. Conversely, intrathecal infusion of fractalkine produced a marked
      p38 activation and mechanical allodynia. SNL also induced a dramatic reduction of
      the membrane-bound fractalkine in the dorsal root ganglion, suggesting a cleavage
      and release of this chemokine after nerve injury. Finally, application of
      fractalkine to spinal slices did not produce acute facilitation of excitatory
      synaptic transmission in lamina II dorsal horn neurons, arguing against a direct
      action of fractalkine on spinal neurons. Collectively, our data suggest that (a)
      fractalkine cleavage (release) after nerve injury may play an important role in
      neural-glial interaction, and (b) microglial CX3CR1/p38 MAPK pathway is critical
      for the development of neuropathic pain.

PMID- 17174527
TI  - Influence of pain treatment by epidural fentanyl and bupivacaine on homing of
      opioid-containing leukocytes to surgical wounds.
AB  - Endogenous opioids released from leukocytes extravasating into injured tissue can
      interact with peripheral opioid receptors to inhibit nociception. Animal studies
      have shown that the homing of opioid-producing leukocytes to the injured site is
      modulated by spinal blockade of noxious input. This study investigated whether
      epidural analgesia (EDA) influences the migration of beta-endorphin (END) and/or
      met-enkephalin (ENK)-containing leukocytes into the subcutaneous wound tissue of
      patients undergoing abdominal surgery. In part I patients received general
      anesthesia combined either with intra- and postoperative EDA (with bupivacaine
      and fentanyl) or with postoperative patient controlled intravenous analgesia
      (PCIA; with the opioid piritramide). In part II patients received general
      anesthesia combined with either epidural fentanyl or bupivacaine which was
      continued postoperatively. Samples of cutanous and subcutanous tissue were taken
      from the wound site at the beginning, at the end and at various times after
      surgery, and were examined by immunohistochemistry for the presence of END and
      ENK. We found that (i) epidural bupivacaine, fentanyl and PCIA provided similar
      and clinically acceptable postoperative pain relief; (ii) compared to PCIA,
      epidural bupivacaine or fentanyl did not change the gross inflammatory reaction
      within the surgical wound; (iii) opioid-containing leukocytes were almost absent
      in normal subcutaneous tissue but migrated to the inflamed wound tissue in
      ascending numbers within a few hours, reaching a peak at about 24 h after
      surgery; (iv) compared to PCIA, EDA resulted in significantly decreased homing of
      END-containing leukocytes to the injured site at 24 h after surgery; and (v) the
      magnitude of this decrease was similar regardless of the epidural medication.
      These findings suggest that nociceptive but not sympathetic neurons are primarily
      involved in the attraction of opioid-containing leukocytes during early stages of
      inflammation.

PMID- 17174528
TI  - Acute systemic inflammation transiently synchronizes clock gene expression in
      equine peripheral blood.
AB  - Peripheral clocks receive timing signals from the master mammalian pacemaker in
      the suprachiasmatic nucleus (SCN) and function to adaptively anticipate daily
      changes that influence local physiology. Evidence suggests that peripheral immune
      activation may act as a resetting signal for circadian clocks in peripheral
      tissues. We wished to investigate whether acute systemic inflammation could
      synchronize clock gene expression in equine peripheral blood, a tissue that does
      not normally oscillate in this species. We report that in vivo administration of
      lipopolysaccharide (LPS) results in significant upregulation of the core clock
      genes Per2 and Bmal1 in equine blood, in association with an acute rise in tumor
      necrosis factor (TNF) alpha and core body temperature compared to vehicle-treated
      control animals. Furthermore, co-administration of LPS and phenylbutazone, a non
      steroidal anti-inflammatory drug (NSAID) known to inhibit prostaglandin (PG) E(2)
      synthesis in the horse, prevents both the febrile response and the synchronized
      increase in clock gene expression. However, the rise in Per2 and Bmal1 expression
      cannot be replicated in equine peripheral blood mononuclear cells (PBMCs) ex vivo
      by treatment with PGE(2), LPS or a heat shock mimicking the in vivo febrile
      response. These results may suggest an indirect communication pathway between
      immune modulators and the molecular machinery of cell clocks in peripheral blood.
      This potential immune feedback regulation of an equine peripheral clock implies a
      role for the circadian system in contributing to innate immune reactions and
      maintaining homeostasis in a tissue that acts as the first line of defense during
      an infectious challenge.

PMID- 17174526
TI  - Intrathecal interleukin-10 gene therapy attenuates paclitaxel-induced mechanical
      allodynia and proinflammatory cytokine expression in dorsal root ganglia in rats.
AB  - Paclitaxel is a commonly used cancer chemotherapy drug that frequently causes
      painful peripheral neuropathies. The mechanisms underlying this dose-limiting
      side effect are poorly understood. Growing evidence supports that proinflammatory
      cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), released
      by activated spinal glial cells and within the dorsal root ganglia (DRG) are
      critical in enhancing pain in various animal models of neuropathic pain. Whether
      these cytokines are involved in paclitaxel-induced neuropathy is unknown. Here,
      using a rat neuropathic pain model induced by repeated systemic paclitaxel
      injections, we examined whether paclitaxel upregulates proinflammatory cytokine
      gene expression, and whether these changes and paclitaxel-induced mechanical
      allodynia can be attenuated by intrathecal IL-1 receptor antagonist (IL-1ra) or
      intrathecal delivery of plasmid DNA encoding the anti-inflammatory cytokine,
      interleukin-10 (IL-10). The data show that paclitaxel treatment induces mRNA
      expression of IL-1, TNF, and immune cell markers in lumbar DRG. Intrathecal IL
      1ra reversed paclitaxel-induced allodynia and intrathecal IL-10 gene therapy both
      prevented, and progressively reversed, this allodynic state. Moreover, IL-10 gene
      therapy resulted in increased IL-10 mRNA levels in lumbar DRG and meninges,
      measured 2 weeks after initiation of therapy, whereas paclitaxel-induced
      expression of IL-1, TNF, and CD11b mRNA in lumbar DRG was markedly decreased.
      Taken together, these data support that paclitaxel-induced neuropathic pain is
      mediated by proinflammatory cytokines, possibly released by activated immune
      cells in the DRG. We propose that targeting the production of proinflammatory
      cytokines by intrathecal IL-10 gene therapy may be a promising therapeutic
      strategy for the relief of paclitaxel-induced neuropathic pain.

PMID- 17174529
TI  - Enabling two persons with multiple disabilities to access environmental stimuli
      and ask for social contact through microswitches and a VOCA.
AB  - This study assessed the combination of two microswitches with a voice output
      communication aid (VOCA) with two persons (an adolescent and a young adult) with
      multiple disabilities. The microswitches allowed the participants to obtain
      direct access to preferred environmental stimuli; the VOCA enabled them to ask
      for caregiver's attention. Initially, the participants were taught to use each of
      the two microswitches individually and then together. Next, they were taught to
      use the VOCA and, eventually, this was available together with the microswitches.
      Results showed that the participants learned to operate the microswitches and the
      VOCA and used all three of them consistently when they were simultaneously
      available. Implications of these findings and the potential role of a VOCA
      combined with conventional microswitches were discussed.

PMID- 17174531
TI  - Puberty, hormones, and sex differences in alcohol abuse and dependence.
AB  - Sex differences in patterns of drinking and rates of alcohol abuse and dependence
      begin to emerge during the transition from late puberty to young adulthood.
      Increases in pubertal hormones, including gonadal and stress hormones, are a
      prominent developmental feature of adolescence and could contribute to the
      progression of sex differences in alcohol drinking patterns during puberty. This
      paper reviews experimental and correlational studies of gonadal and stress
      related hormone changes and their effects on alcohol drinking and other
      associated actions of alcohol. Mechanisms are suggested by which reproductive
      hormones and stress-related hormones may modulate neural circuits within the
      brain reward system to produce sex differences in alcohol drinking patterns and
      vulnerability to alcohol abuse and dependence which become apparent during the
      late pubertal period.

PMID- 17174532
TI  - Altered expression of FHL1, CARP, TSC-22 and P311 provide insights into complex
      transcriptional regulation in pacing-induced atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common progressive disease in patients with
      cardiac arrhythmia. AF is accompanied by complex atrial remodeling and changes in
      gene expression, but only a limited number of transcriptional regulators have
      been identified. Using a low-density cDNA array, we identified 31 genes involved
      in transcriptional regulation, signal transduction or structural components,
      which were either significantly upregulated or downregulated in porcine atria
      with fibrillation (induced by rapid atrial pacing at a rate of 400-600 bpm for 4
      weeks that was then maintained without pacing for 2 weeks). The genes for four
      and a half LIM domains protein-1 (FHL1), transforming growth factor-beta (TGF
      beta)-stimulated clone 22 (TSC-22), and cardiac ankyrin repeat protein (CARP)
      were significantly upregulated, and chromosome 5 open reading frame gene 13
      (P311) was downregulated in the fibrillating atria. FHL1 and CARP play important
      regulatory roles in cardiac remodeling by transcriptional regulation and
      myofilament assembly. Induced mRNA expression of both FHL1 and CARP was also
      observed when cardiac H9c2 cells were treated with an adrenergic agonist.
      Increasing TSC-22 and marked P311 deficiency could enhance the activity of TGF
      beta signaling and the upregulated TGF-beta1 and -beta2 expressions were
      identified in the fibrillating atria. These results implicate that observed
      alterations of underlying molecular events were involved in the rapid-pacing
      induced AF, possibly via activation of the beta-adrenergic and TGF-beta
      signaling.

PMID- 17174534
TI  - Numerical methods for inverse problems in electrooptics of polydisperse colloids.
AB  - In this paper we propose a new method for the determination of the distribution
      of electrical and geometrical particle parameters based on electrooptical
      experimental data. The electrooptical method leads to the solution of inverse ill
      posed problems. The main equations for the determination of the distribution of
      particles on these parameters are presented. To find out the distribution
      functions from the electrooptical experimental data one has to solve the first
      kind Fredholm integral equation corresponding to the problem under study. The
      proposed method of its solution is based on the penalty functions method. The
      results of modelling that let us compare the various numerical methods are
      presented.

PMID- 17174530
TI  - Reduced auditory acuity in rat pups from excess and deficient omega-3 fatty acid
      consumption by the mother.
AB  - Consumption of the nutrients omega-3 fatty acids (omega-3 FA) during pregnancy
      and lactation is considered beneficial to fetal and infant development. It may
      also reduce the incidence and severity of preterm births by prolonging
      gestational length. However several recent human and animal studies have reported
      that over-supplementation with omega-3 FA, especially in the form of fish oil,
      can have adverse effects on fetal and infant development and the auditory
      brainstem response (ABR). Our goal was to assess further the effects of omega-3
      FA excess and deficiency during pregnancy and lactation on the offspring's
      auditory acuity as evidenced by their ABR thresholds. Female Wistar rats were
      given diets that were either deficient, adequate (control) or excess in omega-3
      FA from day 1 of pregnancy through lactation. The offspring were ABR-tested at
      the postnatal age of 24 days. The rat pups in the Excess treatment condition had
      significantly elevated (worse) ABR thresholds, postnatal growth restriction, and
      a trend for increased postnatal mortality in comparison to the Control group. The
      Deficient group was intermediate. In conclusion, excess or deficient amounts of
      omega-3 FA during pregnancy and lactation in the laboratory rat adversely
      affected the offspring's auditory acuity. Postnatal thriving was also adversely
      affected. Consuming or administering large or inadequate amounts of omega-3 FA
      during pregnancy and lactation seems inadvisable because of the potential for
      adverse effects on infant development.

PMID- 17174533
TI  - Volumetric reduction of the corpus callosum in Alzheimer's disease in vivo as
      assessed with voxel-based morphometry.
AB  - Several recent magnetic resonance imaging studies have employed voxel-based
      morphometry (VBM) to detect regional gray matter volume abnormalities in
      Alzheimer's disease (AD). However, investigations of corpus callosum (CC)
      abnormalities in AD using this automated methodology have been scarce, and no VBM
      study investigated correlations between regional CC atrophy and cognitive
      measurements in AD subjects at mild disease stages. We used VBM to compare the
      topography of CC volume differences between 14 AD subjects (MMSE 14-25) and 14
      healthy volunteers. Images were acquired using a 1.5-Telsa scanner, and were
      spatially normalized and segmented using optimized VBM. Statistical comparisons
      were performed using the general linear model. Significant CC atrophy was
      detected in the antero-superior portion of the splenium, the isthmus, the
      anterior and posterior portions of the CC body, and the rostral portion of the
      genu. Voxels showing peak statistical difference were all left-sided (P<0.001,
      uncorrected for multiple comparisons). A cluster of significant positive
      correlation with MMSE scores was seen on the left anterior CC body. Our results
      confirm previous findings of diffuse volumetric CC reductions early in the course
      of AD, and warrant further evaluation of the relevance of atrophic changes in
      anterior CC portions to the cognitive impairments that characterize the disorder.

PMID- 17174535
TI  - Surface modification of poly(tetramethylene adipate-co-terephthalate) membrane
      via layer-by-layer assembly of chitosan and dextran sulfate polyelectrolyte
      multiplayer.
AB  - The improvement of hydrophilicity and hemocompatibility of poly(tetramethylene
      adipate-co-terephthalate) (PTAT) membrane was developed via polyelectrolyte
      multilayers (PEMs) immobilization. The polysaccharide PEMs included chitosan (CS,
      as a positive-charged and antibacterial agent) and dextran sulfate (DS, as a
      negative-charged and anti-adhesive agent) were successfully prepared using the
      aminolyzed PTAT membrane in a layer-by-layer (LBL) self-assembly manner. The
      obtained results showed that the contact angle of as-modified PTAT membranes
      reached to the steady value after four bilayers of coating, hence suggesting that
      the full coverage was achieved. It could be found that the PTAT-PEMs membranes
      with DS as the outmost layer could resist the platelet adhesion and human plasma
      fibrinogen (HPF) adsorption, thereby prolonging effectively the blood coagulation
      times. According to L929 fibroblast cell growth inhibition index, the as-prepared
      PTAT membranes exhibited non-cytotoxic. Overall results demonstrated that such an
      easy, valid and shape-independent processing should be potential for surface
      modification of PTAT membrane in the application of hemodialysis devices.

PMID- 17174536
TI  - [Acute encephalitis in VIH-negative patients: proposals for a national study in
      mainland France].

PMID- 17174538
TI  - Isolation of pure compound R/J/3 from Pluchea indica (L.) Less. and its anti
      amoebic activities against Entamoeba histolytica.
AB  - The plant Pluchea indica is known for its anti-inflammatory, anti-ulcer, anti
      pyretic, hypoglycemic, diuretic and anti-microbial activities besides many other
      pharmacological activities. We have isolated and purified seven compounds from
      the methanolic root extract of this plant by column chromatography. The compounds
      were identified by spectroscopic analyses. The anti-amoebic activities of the
      pure compound R/J/3 was investigated against the HM1 strain of Entamoeba
      histolytica. The compound, R/J/3 showed the most pronounced anti-proliferative
      activity at a dose of 50 microg/ml. It also showed a marked activity on cell
      lysis of trophozoites, 4h after administration. The cell lytic activity was
      compared with metronidazole (5 microg/ml) as positive control.

PMID- 17174539
TI  - Endothelium-dependent vasodilation induced by Hancornia speciosa in rat superior
      mesenteric artery.
AB  - The vasodilator effect of the ethanolic extract of leaves from Hancornia speciosa
      Gomes (HSE) was evaluated in superior mesenteric artery rings. HSE produced a
      concentration-dependent vasodilation (IC50 = 10.8 +/- 4.0 microg/mL) in arterial
      rings pre-contracted with phenylephrine, which was completely abolished in
      endothelium-denuded vessels. Endothelium-dependent vasodilation induced by HSE
      was strongly reduced by L-NAME (100 microM), a nitric oxide (NO) synthase
      inhibitor, but neither by atropine, a muscarinic receptor antagonist (1 microM),
      nor by indomethacin (10 microM), a cyclooxygenase inhibitor. In rings pre
      contracted with 80 mM KCl, the vasodilator effect of HSE was shifted to the right
      and was completely abolished in the presence of L-NAME (100 microM). Similar
      effects were obtained in mesenteric rings pre-contracted with phenylephrine in
      the presence of KCl 25 mM alone or in addition to 100 microM L-NAME. In addition,
      BaCl2 (1 mM) dramatically reduced the vasodilation induced by HSE. Together,
      these findings led us to conclude that HSE induces an endothelium-dependent
      vasodilation in rat mesenteric artery, by a mechanism dependent on NO, on the
      activation of potassium channels and endothelium-derived hyperpolarizing factor
      release. Rutin, identified as a major peak in the HPLC fingerprint obtained for
      HSE, might contribute for the observed vasodilator effect, since it was able to
      induce an endothelium-dependent vasodilation in rat superior mesenteric arteries.

PMID- 17174541
TI  - Microtubule flux: drivers wanted.
AB  - While the metaphase spindle maintains a constant shape and size during cell
      division, its major component microtubules are continuously being polymerized,
      depolymerized and transported towards the two spindle poles in a process called
      microtubule poleward flux. This process has been observed in all metazoan cells.
      Recent studies have indicated that Kinesin-5s, which can drive the relative
      sliding of microtubules, and kinesin-13s, which regulate microtubule
      polymerization, are directly involved in microtubule poleward flux. The
      availability of molecular and chemical tools to perturb protein functions
      together with improvements in imaging and analytical methods have allowed the
      examination of these two kinesins' roles in poleward flux at high temporal and
      spatial resolution. These advances have shed some light on the molecular
      mechanisms that drive microtubule poleward flux.

PMID- 17174540
TI  - Selective and non-selective metalloproteinase inhibitors reduce IL-1-induced
      cartilage degradation and loss of mechanical properties.
AB  - Articular cartilage undergoes matrix degradation and loss of mechanical
      properties when stimulated with proinflammatory cytokines such as interleukin-1
      (IL-1). Aggrecanases and matrix metalloproteinases (MMPs) are thought to be
      principal downstream effectors of cytokine-induced matrix catabolism, and
      aggrecanase- or MMP-selective inhibitors reduce or block matrix destruction in
      several model systems. The objective of this study was to use metalloproteinase
      inhibitors to perturb IL-1-induced matrix catabolism in bovine cartilage explants
      and examine their effects on changes in tissue compression and shear properties.
      Explanted tissue was stimulated with IL-1 for up to 24 days in the absence or
      presence of inhibitors that were aggrecanase-selective, MMP-selective, or non
      selective. Analysis of conditioned media and explant digests revealed that
      aggrecanase-mediated aggrecanolysis was delayed to varying extents with all
      inhibitor treatments, but that aggrecan release persisted. Collagen degradation
      was abrogated by MMP- and non-selective inhibitors and reduced by the aggrecanase
      inhibitor. The inhibitors delayed but did not reduce loss of the equilibrium
      compression modulus, whereas the losses of dynamic compression and shear moduli
      were delayed and reduced. The data suggest that non-metalloproteinase mechanisms
      participate in IL-1-induced matrix degradation and loss of tissue material
      properties.

PMID- 17174542
TI  - Left-right asymmetry: class I myosins show the direction.
AB  - Myosins are actin-based molecular motors that are found in almost all eukaryotes.
      Phylogenetic analysis allows the discrimination of 37 different types of myosins,
      most with unknown functions. Recent work in Drosophila has revealed a crucial
      role for type ID unconventional myosin in left-right asymmetry. Mutations in
      Myosin ID completely reverse the left-right axis (situs inversus), a phenotype
      that is dependent on an intact actin cytoskeleton. How this myosin might orient
      the left-right axis has began to be elucidated by showing that it interacts
      directly with beta-catenin, suggesting that myosin ID interacts with the adherens
      junction to control the direction of organ looping. This is the first
      demonstration of a role of a myosin in body patterning.

PMID- 17174543
TI  - The cell as a material.
AB  - To elucidate the dynamic and functional role of a cell within the tissue it
      belongs to, it is essential to understand its material properties. The cell is a
      viscoelastic material with highly unusual properties. Measurements of the
      mechanical behavior of cells are beginning to probe the contribution of
      constituent components to cell mechanics. Reconstituted cytoskeletal protein
      networks have been shown to mimic many aspects of the mechanical properties of
      cells, providing new insight into the origin of cellular behavior. These networks
      are highly nonlinear, with an elastic modulus that depends sensitively on applied
      stress. Theories can account for some of the measured properties, but a complete
      model remains elusive.

PMID- 17174544
TI  - Evaluation of commercial landscaping mulch for possible contamination from CCA.
AB  - Wood treated with chromated copper arsenate (CCA) is found in construction and
      demolition (C&D) debris, and a common use for wood recycled from C&D debris is
      the production of mulch. Given the high metals concentrations in CCA-treated
      wood, a small fraction of CCA-treated wood can increase the metal concentrations
      in the mulch above regulatory thresholds. The objective of this study was to
      determine the extent of contamination of CCA-treated wood in consumer landscaping
      mulch and to determine whether visual methods or rapid X-ray fluorescence (XRF)
      technology can be used to identify suspect mulch. Samples were collected
      throughout the State of Florida (USA) and evaluated both visually and chemically.
      Visual analysis focused on documenting wood-chip size distribution, whether the
      samples were artificially colored, and whether they contained plywood chips which
      is an indication that the sample was, in part, made from recycled C&D wood.
      Chemical analysis included measurements of total recoverable metals, leachable
      metals as per the standardized synthetic precipitation leaching procedure (SPLP),
      and XRF analysis. Visual identification methods, such as colorant addition or
      presence of plywood, were found effective to preliminarily screen suspect mulch.
      XRF analysis was found to be effective for identifying mulch containing higher
      than 75 mg/kg arsenic. For mulch samples that were not colored and did not
      contain evidence of C&D wood, none exceeded leachable metal concentrations of 50
      microg/L and only 3% exceeded 10 mg/kg for recoverable metals. The majority of
      the colored mulch made from recycled C&D wood contained from 1% to 5% CCA-treated
      wood (15% maximum fraction) resulting in leachable metals in excess of 50
      microg/L and total recoverable metals in excess of 10 mg/kg. The maximum arsenic
      concentration measured in the mulch samples evaluated was 230 mg/kg, which was
      above the Florida residential direct exposure regulatory guideline of 2.1 mg/kg.

PMID- 17174545
TI  - Evaluation of a novel chemical sensor system to detect clinical mastitis in
      bovine milk.
AB  - Automatic detection of clinical mastitis is an essential part of high performance
      and robotic milking. Currently available technology (conductivity monitoring) is
      unable to achieve acceptable specificity or sensitivity of detection of clinical
      mastitis or other clinical diseases. Arrays of sensors with high cross
      sensitivity have been successfully applied for recognition and quantitative
      analysis of other multicomponent liquids. An experiment was conducted to
      determine whether a multisensor system ("electronic tongue") based on an array of
      chemical sensors and suitable data processing could be used to discriminate
      between milk secretions from infected and healthy glands. Measurements were made
      with a multisensor system of milk samples from two different farms in two
      experiments. A total of 67 samples of milk from both mastitic and healthy glands
      were in two sets. It was demonstrated that the multisensor system could
      distinguish between control and clinically mastitic milk samples (p=0.05). The
      sensitivity and specificity of the sensor system (93 and 96% correspondingly)
      showed an improvement over conductivity (56 and 82% correspondingly). The
      multisensor system offers a novel method of improving mastitis detection.

PMID- 17174546
TI  - Evolution and development of neural circuits in invertebrates.
AB  - Developmental mechanisms can shed light on how evolutionary diversity has arisen.
      Invertebrate nervous systems offer a wealth of diverse structures and functions
      from which to relate development to evolution. Individual homologous neurons have
      been shown to have distinct roles in species with different behaviors. In
      addition, specific neurons have been lost or gained in some phylogenetic
      lineages. The ability to address the neural basis of behavior at the cellular
      level in invertebrates has facilitated discoveries showing that species-specific
      behavior can arise from differences in synaptic strength, in neuronal structure
      and in neuromodulation. The mechanisms involved in the development of neural
      circuits lead to these differences across species.

PMID- 17174547
TI  - New optical tools for controlling neuronal activity.
AB  - A major challenge in understanding the relationship between neural activity and
      development, and ultimately behavior, is to control simultaneously the activity
      of either many neurons belonging to specific subsets or specific regions within
      individual neurons. Optimally, such a technique should be capable of both
      switching nerve cells on and off within milliseconds in a non-invasive manner,
      and inducing depolarizations or hyperpolarizations for periods lasting from
      milliseconds to many seconds. Specific ion conductances in subcellular
      compartments must also be controlled to bypass signaling cascades in order to
      regulate precisely cellular events such as synaptic transmission. Light-activated
      G-protein-coupled receptors and ion channels, which can be genetically
      manipulated and targeted to neuronal circuits, have the greatest potential to
      fulfill these requirements.

PMID- 17174548
TI  - Pharmacokinetics in cancer chemotherapy.

PMID- 17174549
TI  - Cyclodextrin production by cyclodextrin glycosyltransferase from Bacillus
      circulans DF 9R.
AB  - Cyclodextrins (CD) are cyclic oligosaccharides with multiple applications in the
      food, pharmaceutical, cosmetic, agricultural and chemical industries. In this
      work, the conditions used to produce CD with cyclodextrin glycosyltransferase
      from Bacillus circulans DF 9R were optimized using experimental designs. The
      developed method allowed the partial purification and concentration of the enzyme
      from the cultural broth and, subsequently, the CD production, using the same
      cassava starch as enzyme adsorbent and as substrate. Heat-treatment of raw starch
      at 70 degrees C for 15 min in the presence of adsorbed cyclodextrin
      glycosyltransferase allowed the starch liquefaction without enzyme inactivation.
      The optimum conditions for CD production were: 5% (w/v) cassava starch, 15 U of
      enzyme per gram of substrate, reaction temperature of 56 degrees C and pH 6.4.
      After 4h, the proportion of starch converted to CD reached 66% (w/w) and the
      weight ratio of alpha-CD:beta-CD:gamma-CD was 1.00:0.70:0.16.

PMID- 17174550
TI  - Pyrazole-based factor Xa inhibitors containing N-arylpiperidinyl P4 residues.
AB  - The synthesis, SAR, pharmacokinetic profile, and modeling studies of both
      monocyclic and fused pyrazoles containing substituted N-arylpiperidinyl P4
      moieties that are potent and selective factor Xa inhibitors will be discussed.
      Fused pyrazole analog 16a, with a 2'-methylsulfonylphenyl piperidine P4 group,
      was shown to be the best compound in this series (FXa Ki = 0.35 nM) based on
      potency, selectivity, and pharmacokinetic profile.

PMID- 17174551
TI  - Analogues of 2-crotonyloxymethyl-(4R,5R,6R)-4,5,6-trihydroxycyclohex-2-enone
      (COTC) with anti-tumor properties.
AB  - The syntheses of three novel analogues of the naturally occurring cytotoxic agent
      COTC are described and the results of bioassays of the target compounds against
      two lung cancer cell lines are presented.

PMID- 17174552
TI  - Signal integration and diversification through the p62 scaffold protein.
AB  - Signal specificity of multifunctional enzymes is achieved through protein-protein
      interactions involving specific domains on scaffold proteins. p62 (also known as
      sequestosome 1) is such a scaffold protein that possesses PB1 and UBA domains,
      and the TRAF6 binding sequence. Proteins recruited to these domains enable p62 to
      integrate kinase-activated and ubiquitin-mediated signaling pathways. The
      biological function of p62 has been studied in diverse systems and processes such
      as osteoclastogenesis, inflammation, differentiation, neurotrophin biology and
      obesity. The availability of mice in which p62 has been genetically inactivated
      is providing new insight into the mechanism and function of p62 at a whole
      organism level.

PMID- 17174553
TI  - Preventing chondrocyte programmed cell death caused by iatrogenic injury.
AB  - Cartilage repair technology is advancing at a rapid pace. However, all techniques
      share a common weakness-unintentional chondrocyte cell death resulting from
      cartilage injury that occurs during preparation of the defect site. The loss of
      chondrocytes at the edge of host cartilage is likely to contribute to failed
      integration of regenerated tissue or grafts to the surrounding cartilage. Recent
      studies have demonstrated that "apoptosis", or programmed cell death (PCD), may
      be responsible for much of the cell death caused by cartilage injury.
      Theoretically, inhibitors of key pathways responsible for PCD could rescue
      chondrocytes and improve the results of cartilage repair surgery. The purpose of
      this study was to test the hypothesis that short-term, intra-articular PCD
      inhibitor treatment can limit chondrocyte death in vivo following simulated
      preparation of host cartilage for a repair procedure. A microcurette was used to
      create full-thickness articular cartilage injuries to the femoral condyles of
      adult New Zealand White rabbits. Animals received daily intra-articular
      injections either with a potent PCD inhibitor or with vehicle alone. Treatment
      with the inhibitor resulted in a significant reduction in the percentage of
      chondrocytes undergoing PCD compared to controls [treated=10.1+/-2.4%;
      controls=26.5+/-3.6%; (p=0.0013)]. These results provide proof of concept for the
      use of PCD inhibitors to enhance the results of cartilage repair surgeries.

PMID- 17174554
TI  - Synthesis and biological evaluation of 4-aryl-5-cyano-2H-1,2,3-triazoles as
      inhibitor of HER2 tyrosine kinase.
AB  - 4-Aryl-5-cyano-2H-1,2,3-triazoles bearing a variety of substituting groups on 4
      phenyl were synthesized. The chemicals, designed as HER2 tyrosine kinase
      inhibitors, were screened for bioactivity of inhibiting growth of breast cancer
      MDA-MB-453 cells. The lowest IC(50) value of inhibiting HER2 tyrosine kinase
      phosphorylation in breast cancer cells is 6.6microM and the IC(50) value of cell
      growth inhibition is correspondingly 30.9microM. The lipophilicity of
      substituting groups on triazoles is the main factor to influence their
      bioactivities.

PMID- 17174555
TI  - The urokinase-type plasminogen activator polymorphism PLAU_1 is a risk factor for
      APOE-epsilon4 non-carriers in the Italian Alzheimer's disease population and does
      not affect the plasma Abeta(1-42) level.
AB  - Sporadic Alzheimer's disease (AD) is the most frequent form of dementia in the
      elderly. A non-conservative polymorphism in the urokinase-type plasminogen
      activator gene (PLAU_1=RS2227564) has been analyzed, but data are conflicting on
      whether it is a risk factor for AD. To clarify whether this genetic variant
      modifies AD risk in the Italian population, we ran a case-control association
      study on 192 AD and 126 age-matched controls. We did not find any association
      between PLAU_1 genotype and AD in the whole AD population, but when we stratified
      our sample by APOE-epsilon4 status, we found a significant association between
      PLAU_1 genotype (C/T+T/T) and APOE-epsilon4 negative AD subjects (p=0.02, chi(2)
      test). The PLAU_1 genotype did not appear to affect the plasma Abeta42
      concentration. Our data support a role for PLAU_1 as an independent genetic risk
      factor for AD in the Italian population for those subjects who do not have the
      APOE-epsilon4 allele.

PMID- 17174558
TI  - What will the 'creatinine kinase' be in 2016?

PMID- 17174556
TI  - The MAPT H1c risk haplotype is associated with increased expression of tau and
      especially of 4 repeat containing transcripts.
AB  - Previously we have shown that the H1c haplotype on the background of the H1 clade
      of haplotypes at the MAPT locus is associated with increased risk for progressive
      supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease
      (AD). Here we replicated the association with AD in an additional autopsy
      confirmed series. We show that this haplotype increases both the expression of
      total MAPT transcript as well as specifically increasing the proportion of 4
      microtubule binding repeat containing transcripts. We discuss these findings both
      in terms of the problems facing the dissection of the etiologies of complex
      traits and the pathogenesis of the tauopathies.

PMID- 17174559
TI  - The effect of sodium nitroprusside infusion on renal function during reperfusion
      period in patients undergoing coronary artery bypass grafting: a prospective
      randomized clinical trial.
AB  - OBJECTIVE: Acute renal failure remains a common and serious complication of
      cardiac surgery. In this randomized trial, we aimed to assess whether sodium
      nitroprusside (SNP) infusion during cardiopulmonary bypass (CPB) could prevent
      renal dysfunction after coronary artery bypass grafting (CABG) surgery. METHODS:
      Between October 2004 and May 2006, 240 consecutive patients with stable angina
      undergoing elective CABG for multi-vessel coronary artery disease were
      prospectively randomized into control (n=116, 72 men, mean age 61.3+/-9.7 years)
      or SNP groups (n=124, 81 men, 60.8+/-10.8 years). SNP group received SNP after
      initiation of rewarming period during CPB at a dose of 0.1mg/kg/h and the
      infusion was concluded by weaning from CPB. The anesthetic and CPB regimes were
      standardized. Blood urea nitrogen (BUN), serum creatinine (SCr), estimated
      glomerular filtration rate (eGFR), creatinine clearance (C(Cr)), urine output,
      serum cardiac specific troponin I (cTnI), creatine kinase cardiac isoenzyme
      (CKMB), and CPK were measured preoperatively and daily until day 5 after surgery.
      RESULTS: There were no differences in baseline levels of BUN, SCr, eGFR, C(Cr),
      cTnI, CKMB, CPK levels and EuroSCORES between the groups. Although the durations
      of cross clamp, CPB times, and postoperative cardiac enzymes were similar in both
      groups; in the control group, there was a significantly lower urine excretion
      during CPB (p=0.002) and the operation (p=0.041). Peak postoperative SCr levels
      were significantly (p=0.001) lower in the SNP group than in the control group
      (1.29+/-0.28 vs 1.42+/-0.34mg/dl). The incidence of >or=50%DeltaSCr was
      significantly higher in the control group when compared with the SNP group (35.3
      vs 13.7%, p<0.001). Development of new C(Cr) less than 50ml/min postoperatively
      was significantly higher in the control group compared with the SNP group (14 vs
      38%, p<0.001). CONCLUSION: SNP administration during rewarming period of non
      pulsatile CPB in patients undergoing CABG surgery is associated with improved
      renal function compared with conventional medical treatment providing adequate
      preload and mean arterial pressures.

PMID- 17174560
TI  - Blunt traumatic injury of the azygous vein diagnosed by computed tomography.

PMID- 17174561
TI  - Mediation of aldose reductase in lipopolysaccharide-induced inflammatory signals
      in mouse peritoneal macrophages.
AB  - Aldose reductase (AR; AKR1B1) a member of aldo-keto reductase super family, that
      we had shown earlier mediates cytotoxic signals induced by high glucose,
      cytokines and growth factors, also mediates the inflammatory signals induced by
      Gram-negative bacterial endotoxin, lipopolysaccharide (LPS). Inhibition of AR by
      three distinct AR inhibitors sorbinil, tolrestat or zopolrestat suppressed the
      LPS-induced production of inflammatory cytokines such as TNF-alpha, IL-6, IL
      1beta, IFN-gamma, and chemokine MCP-1 in murine peritoneal macrophages.
      Inhibition of AR also prevented the production of nitric oxide, and prostaglandin
      E2 and expression of iNOS and Cox-2 proteins. The LPS-induced DNA binding
      activity of NF-kappaB and AP1 were significantly inhibited by AR inhibitors, and
      this effect was mediated through the inhibition of phosphorylation of IkappaB
      alpha, IKK alpha/beta and PKC. These results suggest the therapeutic use of AR
      inhibitors as anti-inflammatory drugs.

PMID- 17174562
TI  - Vasoactive intestinal peptide (VIP) prevents killing of virulent and phoP mutant
      Salmonella typhimurium by inhibiting IFN-gamma stimulated NADPH oxidative
      pathways in murine macrophages.
AB  - Vasoactive intestinal peptide is an immunomodulator with great potential in the
      treatment of inflammatory pathology. In this study, we have examined the effect
      of VIP on the growth dynamics of virulent Salmonella enterica. Serovar
      typhimurium (S. typhimurium) 14028 and 4/74 and an avirulent mutant (14028 phoP)
      in a murine, macrophage cell line (J774.2). In contrast to standard growth
      dynamics, in which phoP mutants do not survive in macrophages, we show that VIP
      (10(-10) M) significantly enhances phoP growth over a 24 h post-infection period
      even when the cells are co-cultured with IFN-gamma. We examined the effect of VIP
      on the generation of NADPH-induced reactive oxygen species (ROS) in Salmonella
      infected/IFN-gamma cultured J774 cells. VIP inhibited gp91 mRNA levels, gp91
      protein and subsequent ROS. The importance of ROS in killing of Salmonella by
      J774 cells was highlighted by experiments in which ROS production by J774 cells
      was inhibited using a conventional inhibitor, N-acetyl-L-cysteine captopril (ACC)
      and in which Salmonella growth significantly increased. Our findings suggest that
      although VIP inhibits inflammatory pathways in myeloid cells it also promotes the
      growth of avirulent (phoP) mutants.

PMID- 17174563
TI  - Interleukin-1 (IL-1) receptor antagonist gene polymorphism in normal weight obese
      syndrome: relationship to body composition and IL-1 alpha and beta plasma levels.
AB  - Interleukin-1 receptor antagonist concentration is upregulated in the plasma of
      patients with obese related disease, and its synthesis is under genetic control.
      We tested the hypothesis that the polymorphism in the interleukin-1 receptor
      antagonist gene second intron might be associated with normal weight obese
      syndrome. The polymorphism of intron 2 in the interleukin-1 receptor antagonist
      gene, containing a variable numbers of a tandem repeat (VNTR), and interleukin
      1alpha and beta plasma levels were evaluated in 110 Caucasian Italian women,
      divided in three groups: non-obese, normal weight obese and preobese-obese. The
      allele 1 frequency was not significantly different in the three groups. The
      alleles 3 and 4 were not observed in any group. The allele 2 frequency in normal
      weight obese woman (12.5%) and preobese-obese (17.5%) groups were significantly
      different in comparison with the non-obese group (6.7%). The allele 5 was
      observed exclusively in non-obese and normal weight obese subjects (13.3 and
      7.5%, respectively). In normal weight obese women, plasma concentrations of
      interleukin-1 alpha and interleukin-1 beta were significantly higher than in non
      obese. The allele 2 was observed in normal weight obese as well as a significant
      association between the increase of interleukin-1 beta plasma amount and the
      allele 2 carrier. Our findings suggest that the allele 2 might be an important
      high-risk genetic marker for normal weight obese syndrome and obesity related
      diseases.

PMID- 17174565
TI  - Characterization of the receptors for axon guidance factor netrin-4 and
      identification of the binding domains.
AB  - Netrins are a family of secreted protein related to laminin and act as tropic
      cues directing axon growth and cell migration during neural development. Netrin-4
      is a novel member of netrin family recently identified in the vertebrate with
      neuritis elongation promoting activity; however, the receptors for netrin-4 are
      still unknown. To better understand the function and signal transduction pathway
      of netrin-4, the potential receptors for netrin-4 were studied in this paper. The
      netrin-4 protein was prepared by introducing a eukaryotic expression vector with
      a secretable alkaline phosphatase tag (AP4) into COS7 cells to allow the
      expression of AP4-netrin4 fusion protein. Axon guidance activity of netrin-4 was
      confirmed by using the cortical explants. After incubation with cultured primary
      cortical neurons, the neurons were distinctly labeled by the AP4-coupled netrin-4
      ligands. In contrast, the binding activity of AP4-netrin4 to neurons could be
      completely competed by the exogenously expressed netrin-4 protein without AP4
      tag, indicating specificity of netrin-4 binding to the potential receptors.
      Moreover, netrin-4 could also bind to CHO cells transfected with the plasmids
      expressing two known receptors for netrin-1, Deleted in Colorectal Cancer (DCC)
      and UNC5 homolog 1 (UNC5H1) respectively. As there are three domains in netrin-4,
      we further tried to narrow down the region containing binding sites with the
      receptors. Interestingly, only the N-terminal domain (LNT) could bind to DCC and
      UNC5H1. A further ligand-receptor binding analysis showed that both the N- and
      the C-terminal domain (NCT) but not the EGF-like (EGFL) domain of netrin-4 could
      bind to the surface of cultured primary neurons, indicating the existence of
      novel receptors for netrin-4. After competed by netrin-4, we confirmed that the
      binding of AP tagged netrin-4 domains to neurons were also netrin-4 dependent.
      The binding activity of the N-terminal domain of netrin-4 is about 3-fold higher
      than that for the C-terminal domain. In summary, our data here indicated that the
      two known receptors for netrin-1, DCC and UNC5H1, are also receptors for netrin
      4, while only LNT but not EGFL and NCT is the key domain for specific binding. In
      addition, there are novel receptors for netrin-4, where both LNT and NCT but not
      EGFL are key domains for binding.

PMID- 17174566
TI  - Disparities in psychological distress across education and sex: a longitudinal
      analysis of their persistence within a cohort over 19 years.
AB  - PURPOSE: Disparities in psychological distress across socioeconomic status and
      sex persist throughout adulthood as cohorts age. In this study, we investigate
      the extent to which this persistence represents either (i) a single set of
      individuals who at the start of adulthood show distress that is chronic and long
      lasting or (ii) different sets of individuals that have a staggered onset of
      short-term distress throughout adulthood. METHODS: We use path analysis on data
      from the National Child Development Study, a longitudinal cohort study that
      assessed psychological distress at ages 23, 33, and 42 years. RESULTS: About 80%
      of distress disparities at age 42 result from chronic distress that was present
      in a single set of individuals at least 19 years earlier at the beginning of
      adulthood. CONCLUSIONS: These results support a targeted approach to the
      reduction of distress disparities that focuses on young adults with high levels
      of distress and seeks to improve their long-term mental health.

PMID- 17174564
TI  - Localization of glutamate receptors to distal dendrites depends on subunit
      composition and the kinesin motor protein KIF17.
AB  - Correct glutamate receptor localization in neurons is crucial for
      neurotransmission in the brain. Here we investigated the mechanisms underlying
      localization of kainate GluR5 receptors to dendrites in cultured hippocampal
      neurons. We find that the GluR5 distribution depends on association with GluR6
      and KA2 subunits. The GluR5 subunit was expressed in distal dendrites only when
      GluR6 and KA2 subunits were present, whereas it was restricted to proximal
      dendrites in the absence of these subunits. The overlap between GluR5
      distribution and the organization of microtubules in dendrites led us to examine
      whether KIF17, a microtubule motor protein expressed in distal dendrites, is
      involved in GluR5 localization to distal dendrites. We show here, for the first
      time that the microtubule motor protein KIF17 interacts with GluR6 and KA2
      subunits and is required for GluR5 localization to distal dendrites, defining a
      novel mechanism that controls receptor localization in neurons.

PMID- 17174567
TI  - Lack of autodisable syringe use and health care indicators are associated with
      high HIV prevalence: an international ecologic analysis.
AB  - PURPOSE: A growing body of evidence strongly suggests that unsafe health care is
      an important factor driving the human immunodeficiency virus (HIV) epidemic in
      sub-Saharan Africa. We investigate whether nonuse of autodisable syringes and
      other health care indicators predict national HIV prevalence. METHODS: These
      ecologic analyses use countries as study units in descriptive analyses and
      regression analyses. Two sets of observations are used: (i) all low- and lower
      middle-income countries, and (ii) all sub-Saharan African countries with
      available data. RESULTS: In the descriptive analysis, health care indicators
      (health expenditures, vaccination coverage, and use of autodisable syringes) have
      a U-shaped relationship with HIV prevalence in the larger sample. Greater density
      of physicians is associated with lower HIV prevalence. In sub-Saharan Africa,
      antenatal care coverage is associated with increasing HIV prevalence. In
      regression analyses, nonuse of autodisable syringes is associated robustly with
      greater HIV prevalence in all models. For the larger sample, greater HIV
      prevalence also is associated with higher Gini Index, less female economic
      activity, less urbanization, and less percentage of Muslims. In sub-Saharan
      Africa, tetanus vaccination coverage has a U-shaped association with HIV
      prevalence. Low physician density and percentage of Muslims are associated with
      HIV prevalence. Other economic and health care indicators and epidemic age are
      not significant correlates of HIV prevalence. CONCLUSIONS: This analysis adds to
      the other sources of evidence for health care transmission of HIV (in sub-Saharan
      Africa and regions with similar epidemiologic characteristics) by showing that
      health care indicators (failure to use autodisable syringes and greater tetanus
      coverage) are associated robustly with greater HIV prevalence. We recommend that
      resources be reallocated to address health care transmission of HIV/acquired
      immunodeficiency syndrome.

PMID- 17174568
TI  - Body size and risk for breast cancer in relation to estrogen and progesterone
      receptor status in Japan.
AB  - PURPOSE: The aim of this study is to examine the association of height, weight,
      and body mass index (BMI) with breast cancer and its hormone receptor-defined
      subtype in a low-risk population. METHODS: We identified 441 newly diagnosed
      cases of breast cancer during a 9.9-year follow-up of a population-based cohort
      consisting of 55,537 women aged 40 to 69 years. Body size was assessed by using a
      self-administered questionnaire. RESULTS: We found a significant positive
      association of height and marginally significant positive associations of weight
      and BMI with breast cancer in postmenopausal women. Weight and BMI were
      associated more strongly with estrogen receptor-positive (ER+) than ER-negative
      (ER-) breast cancer in postmenopausal women. BMI was related significantly to
      increased risk for ER+ (hazard ratio [HR] per BMI increment of 1 kg/m2, 1.08; 95%
      confidence interval [CI], 1.01-1.15), but not ER- breast cancer (HR per BMI
      increment of 1 kg/m2, 0.95; 95% CI, 0.84-1.06; p for difference of HRs=0.048).
      CONCLUSIONS: The present study suggests that height, weight, and BMI are
      associated with increased risk for breast cancer among postmenopausal women in
      Japan. The positive association of weight and BMI might be limited to ER+ breast
      cancer.

PMID- 17174569
TI  - RE: Hirsch C, Anderson ML, Newman A, Kop W, Jackson S, Gottdiener J, et al, for
      the Cardiovascular Health Study Research Group. The association of race with
      frailty: The Cardiovascular Health Study. Ann Epidemiol. 2006;16:545-553.

PMID- 17174570
TI  - Premorbid (early life) IQ and later mortality risk: systematic review.
AB  - PURPOSE: Studies of middle-aged and particularly older-aged adults found that
      those with higher scores on tests of IQ (cognitive function) had lower rates of
      later mortality. Interpretation of such findings potentially is hampered by the
      problem of reverse causality: such somatic diseases as diabetes or hypertension,
      common in older adults, can decrease cognitive function. Studies that provide
      extended follow-up of the health experience of individuals who had their
      (premorbid) IQ assessed in childhood and/or early adulthood minimize this
      concern. The purpose of the present report is to systematically locate, evaluate,
      and interpret the findings of all such studies. METHODS: We systematically
      identified individual-level studies linking premorbid IQ with later mortality by
      using four approaches: search of electronic databases (MEDLINE, EMBASE, and
      PSYCHINFO); scrutiny of the reference sections of identified reports; search of
      our own files; and contact with researchers in the field. Study quality was
      assessed by using predefined criteria. RESULTS: Nine cohort studies met the
      inclusion criteria. Overall, study quality was moderate. All reports showed an
      inverse IQ-mortality relation; i.e., higher IQ scores were associated with
      decreased mortality risk. The nature of this relation (i.e., dose-response or
      threshold) and whether it differs by sex was unclear. The IQ-mortality
      association did not appear to be explained by reverse causality or selection
      bias. Confounding by other early-life factors also did not seem to explain the
      association, although some studies were not well characterized in this regard.
      Adult socioeconomic position appeared to mediate the IQ-mortality association in
      some studies, but this was not a universal finding. CONCLUSIONS: In all studies,
      higher IQ in the first two decades of life was related to lower rates of total
      mortality in middle to late adulthood. Some plausible mechanistic pathways exist,
      but further examination is required. The precise nature of the IQ-mortality
      relation (particularly in ethnic minorities and women) and the link between IQ
      and disease-specific outcomes also warrants further research.

PMID- 17174571
TI  - Molecular cloning, characterization and expression of a masquerade-like serine
      proteinase homologue from black tiger shrimp Penaeus monodon.
AB  - A full-length cDNA of a masquerade-like serine proteinase homologue (PmMasSPH) of
      Penaeus monodon was cloned and characterized by rapid amplification cDNA end
      (RACE) method. The complete cDNA sequence of 1958bp contains an open reading
      frame (ORF) of 1572bp, encoding a 523 amino acid protein including a 19 amino
      acid signal peptide. The calculated molecular mass of the mature protein (504
      amino acids) is 51.58kDa with an estimated pI of 4.86. PmMasSPH has most of the
      structural characteristics of insect prophenoloxidase activating factors (PPAFs)
      (the N-terminal clip domain and the C-terminal serine proteinase-like domain) but
      in the N-terminal region there are extensive glycine-rich repeats (LGGQGGG).
      Sequence comparison showed that the deduced amino acid of PmMasSPH has an overall
      similarity of 69%, 68% and 61% to those of Apis mellifera PPAF, Callinectes
      sapidus PPAF and Tenebrio molitor PPAF, respectively. A neighbour-joining tree
      revealed a clear differentiation of each species and also indicated that PmMasSPH
      and C. sapidus PPAF are closely related phylogenetically. In situ hybridisation
      and real-time RT-PCR analyses showed that PmMasSPH transcript in haemocytes of P.
      monodon increased within 24h after Vibrio harveyi injection.

PMID- 17174572
TI  - Improved reliability of hippocampal atrophy rate measurement in mild cognitive
      impairment using fluid registration.
AB  - MRI-derived rates of hippocampal atrophy may serve as surrogate markers of
      disease progression in mild cognitive impairment (MCI). Manual delineation is the
      gold standard in hippocampal volumetry; however, this technique is time-consuming
      and subject to errors. We aimed to compare regional non-linear (fluid)
      registration measurement of hippocampal atrophy rates against manual delineation
      in MCI. Hippocampi of 18 subjects were manually outlined twice on MRI scan-pairs
      (interval+/-SD: 2.01+/-0.11 years), and volumes were subtracted to calculate
      change over time. Following global affine and local rigid registration, regional
      fluid registration was performed from which atrophy rates were derived from the
      Jacobian determinants over the hippocampal region. Atrophy rates as derived by
      fluid registration were computed using both forward (repeat onto baseline) and
      backward (baseline onto repeat) registration. Reliability for both methods and
      agreement between methods was assessed. Mean+/-SD hippocampal atrophy rates
      (%/year) derived by manual delineation were: left: 2.13+/-1.62; right: 2.36+/
      1.78 and for regional fluid registration: forward: left: 2.39+/-1.68; right:
      2.49+/-1.52 and backward: left: 2.21+/-1.51; right: 2.42+/-1.49. Mean hippocampal
      atrophy rates did not differ between both methods. Reliability for manual
      hippocampal volume measurements (cross-sectional) was high (intraclass
      correlation coefficient (ICC): baseline and follow-up, left and right, >0.99).
      However, the resulting ICC for manual measurements of hippocampal volume change
      (longitudinal) was considerably lower (left: 0.798; right: 0.850) compared with
      regional fluid registration (forward: left: 0.985; right: 0.988 and backward:
      left: 0.975; right: 0.989). We conclude that regional fluid registration is more
      reliable than manual delineation in assessing hippocampal atrophy rates, without
      sacrificing sensitivity to change. This method may be useful to quantify
      hippocampal volume change, given the reduction in operator time and improved
      precision.

PMID- 17174573
TI  - Memory and frontal lobe functions; possible relations with dopamine D2 receptors
      in the hippocampus.
AB  - Cerebral cortical regions are thought to be important for cognitive functions
      such as memory and executive function. Although the functional associations
      between dopamine D2 receptors and motor and cognitive functions have been
      extensively examined in the striatum using positron emission tomography (PET),
      the role of dopamine D2 receptors in extrastriatal regions has been unexplored.
      We aimed to investigate the relationship between dopamine D2 receptors in
      extrastriatal regions and the performance of a broad spectrum of cognitive
      functions including memory, language, attention, and executive function in
      healthy subjects. Extrastriatal dopamine D2 receptors were measured in 25 male
      subjects using PET with [(11)C]FLB457. After the PET scans, a battery of
      neuropsychological tests was administered to all subjects. We found that the
      binding potential (BP) of [(11)C]FLB457 in the hippocampus was positively
      correlated with memory function. Furthermore, BP of [(11)C]FLB457 in the
      hippocampus, but not in the prefrontal cortex, was associated with frontal lobe
      functions such as executive function and verbal fluency. Our findings suggest
      that dopamine D2 receptors in the hippocampus might affect the local hippocampal
      function, but also brain functions outside the hippocampus such as the prefrontal
      cortex.

PMID- 17174574
TI  - Asymmetry in dopamine D(2/3) receptors of caudate nucleus is lost with age.
AB  - Molecular and functional imaging techniques reveal evidence for lateralization of
      human cerebral function. Based on animal data, we hypothesized that asymmetry in
      dopamine neurotransmission declines during normal aging. In order to test this
      hypothesis, we measured dopamine D2/3 receptor availability with
      [18F]desmethoxyfallypride-PET (DMFP) in putamen and caudate nucleus (NC) of 21
      healthy, right-handed males (24-60 years; 35+/-10). For volumetric analysis, high
      resolution T1-weighted MR-images were obtained in 18 of the PET-subjects in order
      to assess possible age-related decreases in NC and putamen volume. The calculated
      DMFP binding potentials (BP) showed a right-ward asymmetry in NC of young
      subjects that decreased with age (r = 0.577, p = 0.006; Pearson correlation; two
      tailed). An age-independent analysis showed a right-ward asymmetry in NC of the
      whole subject group (left: 1.49+/-0.35; right: 1.65+/-0.43 [mean+/-S.D.]; p =
      0.020). No such side lateralization or age-effects could be found in the putamen.
      Volumes tended to be asymmetric in the putamen (right: 4.85+/-0.56 cm3; left:
      4.64+/-0.86 cm3 [mean+/-S.D.]; p = 0.063), but not in NC. The decline of putamen
      volume during aging was significant in the right putamen (r = -0.613; p = 0.007;
      Pearson correlation; two-tailed). There were no other significant correlations
      between striatal volumes and age or BP. Because ventral striatal dopamine
      neurotransmission is involved in cognitive processes, this loss of physiological
      asymmetry in NC dopamine transmission during aging might be involved in age
      related declines of cognitive performance.

PMID- 17174575
TI  - Thalamo-cortical connectivity in children born preterm mapped using probabilistic
      magnetic resonance tractography.
AB  - Our aim was to investigate the feasibility of studying white matter tracts and
      connections between the thalamus and the cortex in 2-year-old infants who were
      born preterm by probabilistic magnetic resonance (MR) tractography. Using this
      approach, we were able to visualize and quantify connectivity distributions in a
      number of white matter tracts, including the corticospinal tracts, optic
      radiations, fibers of the genu and splenium of the corpus callosum, superior
      longitudinal fasciculus and inferior fronto-occipital fasciculus, and to map the
      distribution within thalamus of fibers connecting to specific cortical regions.
      In eleven infants with no MR evidence of focal cerebral lesions and appropriate
      neurodevelopment as shown by general quotient (GQ) scores above 100, we mapped
      cortical connections to the thalamus that appeared similar to those reported in
      adults. However, in a proof-of-principle experiment, we examined one further
      child with marked white matter abnormalities and found that the volume and
      pattern of thalamo-cortical connections were severely disrupted. This technique
      promises to be a useful tool for assessing connectivity in the developing brain
      and in infants with lesions.

PMID- 17174576
TI  - Global eukaryote phylogeny: Combined small- and large-subunit ribosomal DNA trees
      support monophyly of Rhizaria, Retaria and Excavata.
AB  - Resolution of the phylogenetic relationships among the major eukaryotic groups is
      one of the most important problems in evolutionary biology that is still only
      partially solved. This task was initially addressed using a single marker, the
      small-subunit ribosomal DNA (SSU rDNA), although in recent years it has been
      shown that it does not contain enough phylogenetic information to robustly
      resolve global eukaryotic phylogeny. This has prompted the use of multi-gene
      analyses, especially in the form of long concatenations of numerous conserved
      protein sequences. However, this approach is severely limited by the small number
      of taxa for which such a large number of protein sequences is available today. We
      have explored the alternative approach of using only two markers but a large
      taxonomic sampling, by analysing a combination of SSU and large-subunit (LSU)
      rDNA sequences. This strategy allows also the incorporation of sequences from non
      cultivated protists, e.g., Radiozoa (=radiolaria minus Phaeodarea). We provide
      the first LSU rRNA sequences for Heliozoa, Apusozoa (both Apusomonadida and
      Ancyromonadida), Cercozoa and Radiozoa. Our Bayesian and maximum likelihood
      analyses for 91 eukaryotic combined SSU+LSU sequences yielded much stronger
      support than hitherto for the supergroup Rhizaria (Cercozoa plus Radiozoa plus
      Foraminifera) and several well-recognised groups and also for other problematic
      clades, such as the Retaria (Radiozoa plus Foraminifera) and, with more moderate
      support, the Excavata. Within opisthokonts, the combined tree strongly confirms
      that the filose amoebae Nuclearia are sisters to Fungi whereas other Choanozoa
      are sisters to animals. The position of some bikont taxa, notably Heliozoa and
      Apusozoa, remains unresolved. However, our combined trees suggest a more deeply
      diverging position for Ancyromonas, and perhaps also Apusomonas, than for other
      bikonts, suggesting that apusozoan zooflagellates may be central for
      understanding the early evolution of this huge eukaryotic group. Multiple protein
      sequences will be needed fully to resolve basal bikont phylogeny. Nonetheless,
      our results suggest that combined SSU+LSU rDNA phylogenies can help to resolve
      several ambiguous regions of the eukaryotic tree and identify key taxa for
      subsequent multi-gene analyses.

PMID- 17174577
TI  - Tracking problems and possible solutions in the quantitative determination of
      small molecule drugs and metabolites in biological fluids using liquid
      chromatography-mass spectrometry.
AB  - During the last decade, quantification of low molecular weight molecules using
      liquid chromatography-tandem mass spectrometry in biological fluids has become a
      common procedure in many preclinical and clinical laboratories. This overview
      highlights a number of issues involving "small molecule drugs", bioanalytical
      liquid chromatography-tandem mass spectrometry, which are frequently encountered
      during assay development. In addition, possible solutions to these issues are
      proposed with examples in some of the case studies. Topics such as
      chromatographic peak shape, carry-over, cross-talk, standard curve non-linearity,
      internal standard selection, matrix effect, and metabolite interference are
      presented. Since plasma is one of the most widely adopted biological fluid in
      drug discovery and development, the focus of this discussion will be limited to
      plasma analysis. This article is not intended to be a comprehensive overview and
      readers are encouraged to refer to the citations herein.

PMID- 17174578
TI  - Antioxidant N-acetyl-L-cysteine inhibits erythropoietin-induced differentiation
      of erythroid progenitors derived from mouse fetal liver.
AB  - To determine the role of reactive oxygen species in erythroid differentiation, we
      investigated the effects of an antioxidant, N-acetyl-L-cysteine (NAC), on the
      differentiation of erythroid progenitors derived from mouse fetal liver. In
      response to erythropoietin (Epo), erythroid progenitors undergo differentiation
      in vitro and express erythroid-specific genes such as betamajor-globin, Alas2,
      MafK, p45, Eklf, and Gata1. Expression of these genes was decreased in the
      presence of NAC, whereas the expression of c-myb, which is downregulated during
      erythroid differentiation, remained constant. Moreover, NAC treatment inhibited
      an increase in the number of cells expressing high levels of erythroid-specific
      antigen TER119. Treatment with another antioxidant, pyrrolidine dithiocarbamate,
      also caused the attenuation of TER119 expression. These results suggest that
      reactive oxygen species are involved in Epo-mediated erythroid differentiation.

PMID- 17174579
TI  - Nuclear scintigraphy: uses and limitations.

PMID- 17174580
TI  - Theileriosis and the tick control conundrum: a better way forward?

PMID- 17174581
TI  - Radiation-damping effects in a birdcage resonator with hyperpolarised 3He gas NMR
      at 1.5 T.
AB  - The presence and diagnosis of radiation damping could have major implications in
      NMR experiments with hyperpolarised gases, where accurate knowledge of the flip
      angle is imperative. In this work radiation damping was observed and investigated
      in a low-pass birdcage resonator (Q=250) with samples of hyperpolarised 3He at
      1.5 T. With an initially highly polarised (P=38%) sample of 3He in a spherical
      cell, the observed FID had a distorted line shape with a spectral line width that
      was three times that of the same sample in a virtually depolarised state (1 Hz
      line width for P<1%). Moreover a linear relation between the sample's
      magnetisation (M0) and the line width of the spectrum was observed which is
      indicative of radiation damping. With highly polarised samples, significant
      radiation damping was observed and the effect was a lower than expected rate of
      depletion of M0 in RF flip angle calibration experiments, which led to
      significant underestimate of the RF flip angle. To our knowledge this is the
      first report of radiation damping in a birdcage resonator with samples
      hyperpolarised or otherwise. Experimental observation of radiation damping could
      be used as means of measuring coil efficiency as an alternative to the
      geometrical filling factor (eta) the definition of which is open to question for
      a birdcage resonator. Estimates of the birdcage filling factor from the measured
      damping time constants (eta(RD)=0.4%) are compared to those derived from
      electromagnetic energy ratios (eta(E)=1.6%) and metallic sphere frequency shift
      methods (eta(fs)=1.4%). These figures are much lower than the simple volume
      geometrical upper limit of eta(v)=3.7% derived from the ratio of cell volume to
      total coil volume (shield included). The physical explanation for this shortfall
      is that the bulk of the magnetic energy stored in the birdcage is spatially
      distributed predominantly between the rungs and the shield, and not in the coil
      centre where the sample is placed and where the B1+ field has its highest spatial
      homogeneity.

PMID- 17174582
TI  - Modelling and study of cyclosporin A and related compounds in complexes with a
      Trypanosoma cruzi cyclophilin.
AB  - Cyclophilins (CyPs) are enzymes involved in protein folding, catalyzing the
      isomerisation of peptidyl prolyl bonds in proteins and peptides between the cis-
      and trans-conformations. They are also the major cellular target for the
      immunosuppressive drug Cyclosporin A (CsA). In Trypanosoma cruzi, the most
      abundantly expressed CyP is an isoform of 19 kDa, TcCyP19, in which the enzymatic
      activity is inhibited by CsA. Among a reported set of CsA analogues, two non
      immunosuppressive compounds, H-7-94 and F-7-62, proved to be the best inhibitors
      of TcCyP19 enzymatic activity as well as the most efficient trypanocidal drugs.
      With the objective of analysing, at the molecular level, how the structural
      differences between the three above-mentioned inhibitors justify their different
      inhibitory activity on TcCyP19, three-dimensional molecular modelling structures
      were generated to computationally simulate behaviours and interactions. An energy
      minimized model of each binary complex in water with ions was obtained. These
      models were then used as starting point for molecular dynamic simulations,
      performed with GROMOS96 program. With the resulting set of co-ordinates and
      energies, a comparison of the interaction between CsA and both CsA analogues in
      T. cruzi and human cyclophilins were performed. Within the different magnitudes
      analysed, the total potential complex energy exhibited the best correlation with
      the experimental data. The results obtained in this study support the use of this
      methodology when designing new lead inhibitor compounds.

PMID- 17174584
TI  - Spinal muscle evaluation in healthy individuals and low-back-pain patients: a
      literature review.
AB  - This article reviews available techniques for spinal muscle investigation, as
      well as data on spinal muscles in healthy individuals and in patients with low
      back pain. In patients with chronic low back pain, medical imaging studies show
      paraspinal muscle wasting with reductions in cross-sectional surface area and
      fiber density. In healthy individuals, the paraspinal muscles contain a high
      proportion of slow-twitch fibers (Type I), reflecting their role in maintaining
      posture. The proportion of Type I fibers is higher in females, leading to better
      adaptation to aerobic exertion compared to males. Abnormalities seen in
      paraspinal muscles from patients with chronic low back pain include marked Type
      II fiber atrophy, conversion of Type I to Type II fibers, and an increased number
      of nonspecific abnormalities. Limited data are available from magnetic resonance
      spectroscopy used to investigate muscle metabolism and from near infrared
      spectroscopy used to measure oxygen uptake by the paraspinal muscles. Surface
      electromyography in patients with chronic low back pain shows increased
      paraspinal muscle fatigability, often with abolition of the flexion-relaxation
      phenomenon.

PMID- 17174585
TI  - When should we use TNF antagonists in children with rheumatic disease?

PMID- 17174586
TI  - Cardiovascular disease in rheumatoid arthritis: single-center hospital-based
      cohort study in France.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) was independently associated with
      cardiovascular events in several studies, most of which were conducted in the US.
      OBJECTIVES: To estimate the risk of cardiovascular events in a cohort of RA
      patients recruited at a hospital in France, to identify cardiovascular risk
      factors, and to measure the severity of cardiovascular events. METHODS: Two
      hundred and thirty-nine patients admitted between January 1, 1998, and March 31,
      1999, for RA meeting American College of Rheumatology criteria, with a negative
      history for cardiovascular events, were sent a questionnaire in 2004 to evaluate
      the occurrence of myocardial infarction, stroke, or cardiovascular death.
      RESULTS: During the mean follow-up of 5.4+/-1.8 years, there were 10 cases of
      myocardial infarction (0.8%/year), 3 cases of stroke (0.2%/year), and 9
      cardiovascular deaths (0.7%/year). Of the 10 patients who experienced myocardial
      infarction, 5 had clinical symptoms of heart failure and 4 died from
      cardiovascular causes. Independent risk factors for cardiovascular events were
      older age (relative risk [RR], 2.5/10 years; 95% confidence interval [95%CI], 1.4
      4.2), male gender (RR, 5.1; 95%CI, 1.8-14.6), treated hypertension (RR, 4.3;
      95%CI, 1.4-13.2), and treated hypercholesterolemia (RR, 6.0; 95%CI, 1.8-20.7).
      CONCLUSION: Our data suggest a higher risk of cardiovascular events in patients
      with RA compared to the general population in France (0.1-0.5%/year for
      myocardial infarction and 0.07%/year for stroke in the age group covered by our
      cohort). Cardiovascular events in the patients with RA seemed unusually severe.
      Patients with RA should be carefully screened for conventional cardiovascular
      risk factors.

PMID- 17174587
TI  - A forgotten challenge when treating osteoporosis: getting patients to take their
      meds.

PMID- 17174588
TI  - Objective response detection technique in frequency-domain for reflecting changes
      in MLAEP.
AB  - The mid-latency auditory evoked potential (MLAEP) occurs within the interval 10
      100ms post-stimulus and exhibits morphological changes due to coma, general
      anaesthesia and neurological and psychiatric diseases. This work evaluates an
      objective response detection technique in the frequency domain, the magnitude
      squared coherence (kappa(2)(f)), in reflecting MLAEPs changes in amplitude and
      latencies. Both simulation and EEG data were used in this investigation. The EEG
      during auditory stimulation in 10 volunteers under propofol-induced anaesthesia
      was acquired. Based on the null hypothesis of non-existing response, critical
      values have been derived in order to detect the auditory response. The
      alternative hypothesis was used to infer about maximal-response frequencies as
      well as to derive confidence intervals for the estimated values of kappa(2)(f)
      during anaesthesia. Changes in both simulated and real MLAEPs could be tracked by
      kappa(2)(f), even for low SNR. High degree of cortical activation occurred
      predominantly between 30 and 90Hz. This finding could be related to the sensory
      originated phase-locked oscillation in the gamma band (30-70Hz). Hence, for
      applications where changes on MLAEPs should be assessed, the use of kappa(2)(f)
      as an objective statistical response detection technique is worth to be applied.

PMID- 17174589
TI  - A two phase harmonic model for left ventricular function.
AB  - A minimal model for mechanical motion of the left ventricle is proposed. The
      model assumes the left ventricle to be a harmonic oscillator with two distinct
      phases, simulating the systolic and diastolic phases, at which both the amplitude
      and the elastic constant of the oscillator are different. Taking into account the
      pressure within the left ventricle, the model shows qualitative agreement with
      functional parameters of the left ventricle. The model allows for a natural
      explanation of heart failure with preserved systolic left ventricular function,
      also termed diastolic heart failure. Specifically, the rise in left ventricular
      filling pressures following increased left-ventricular wall stiffness is
      attributed to a mechanism aimed at preserving heart rate and cardiac output.

PMID- 17174590
TI  - Immigration, ethnicity, and accessibility to culturally diverse family
      physicians.
AB  - The study concerns ethnicity, spatial equity, and healthcare access in the
      context of diversity and integration. The paper first explores how Chinese
      immigrants in the Toronto Census Metropolitan Area choose between ethnic Chinese
      family physicians and other family physicians, based on a probability survey. It
      then applies and modifies gravity-type accessibility measures, of which a special
      type is the so-called floating catchment area (FCA) method, to evaluate three
      types of geographical accessibility in family physician utilization. The study
      suggests a certain degree of spatial inequality among Chinese immigrants in
      accessing culturally sensitive care. The paper yields important methodological
      and policy implications.

PMID- 17174591
TI  - Chemical genetic approaches to probing cell death.
AB  - Chemical genetics has arisen as a tool for the discovery of pathways and proteins
      in mammalian systems. This approach, comprising small-molecule screening combined
      with biochemical and genomic target identification methods, enables one to assess
      which proteins are involved in regulating a particular phenotype. Applied to cell
      death, this strategy can reveal novel targets and pathways regulating the demise
      of mammalian cells. Numerous diseases have been linked to the loss of regulation
      of cell death. Defining the mechanisms governing cell death in these diseases
      might lead to the discovery of therapeutic agents and targets and provide a
      richer understanding of the mortality of living systems. Recent advances include
      the discovery of novel small molecules regulating cell death pathways --
      necrostatin and erastin -- as well as the elucidation of the mechanism of death
      induced in cancer cells by the cytotoxic agent Apratoxin A.

PMID- 17174593
TI  - Assessment of local genotoxic effects of formaldehyde in humans measured by the
      micronucleus test with exfoliated buccal mucosa cells.
AB  - Volunteers (10 women, 11 men) were exposed to formaldehyde (FA) vapors for 4h per
      day over a period of 10 working days under strictly controlled conditions.
      Exposure varied randomly each day from constant 0.15 ppm up to 0.5 ppm with four
      peaks of 1.0 ppm for 15 min each (13.5 ppm h cumulative exposure over 10 working
      days). FA was masked on four days by co-exposure to ethyl acetate. During
      exposure, subjects had to perform bicycle exercises (about 80 W) three times for
      15 min. Buccal smears were prepared 1 week before the start of the study (control
      1), at the start of the study before the first exposure (control 2), at the end
      of the exposure period of 10 days and 7, 14 and 21 days thereafter. Two thousand
      cells per data point were analyzed for the presence of micronuclei (MN) and the
      frequency of MN per 1000 cells was determined on slides coded by an independent
      quality-assurance unit. No significant increase in the frequency of MN was
      measured at any time point after the end of the exposure. Twenty-one days after
      the end of the exposure MN frequencies were significantly lower in comparison
      with control 1. This study, which was performed under GLP-like conditions,
      clearly indicates that FA does not induce MN in buccal mucosa cells after peak
      exposures up to 1 ppm and a cumulative exposure of 13.5 ppm h over 2 weeks.

PMID- 17174592
TI  - Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in
      rat bone-marrow after sub-chronic oral dosing.
AB  - Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant
      synergist in a number of household products, as a fining agent in glass
      manufacture, and as a catalyst in the manufacture of various types of polyester
      plastics. It does not induce point mutations in bacteria or mammalian cells, but
      is able to induce chromosomal aberrations (CA) in cultured cells in vitro.
      Although no CA or micronuclei (MN) have been induced after acute oral dosing of
      mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one
      report, but did not result in increased MN in another. In order to further
      investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats
      for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of
      toxicity in the Sb2O3-exposed animals except for some reductions in body-weight
      gain in the top dose group. Toxicokinetic measurements in a separate study
      confirmed bone-marrow exposure, and at higher levels than would have been
      achieved by single oral dosing. Large numbers of cells were scored for CA (600
      metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN
      in Sb2O3-treated rats were very similar to controls, and not biologically or
      statistically different, at all doses. These results provide further indication
      that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral
      administration at high doses close to the maximum tolerated dose.

PMID- 17174594
TI  - Cruciferous vegetables and lung cancer.

PMID- 17174595
TI  - World Wide Web hepatitis B virus resources.
AB  - BACKGROUND: Hepatitis B virus infection is a global public health issue, often
      under-discussed due to social prejudices related to its mode of transmission. The
      World Wide Web, an increasingly popular means of dissemination of health-related
      information, can serve continuing medical practitioner awareness and enhance
      public health literacy. OBJECTIVE: The authors sought to investigate the
      existence of, and evaluate the content of websites offering information on
      hepatitis B. STUDY DESIGN: Sites were selected by certain criteria (sponsor,
      language options, free access, validation of content by independent medical and
      non-medical personnel), which unavoidably rendered the lists subjective. RESULTS:
      At least three medical personnel-oriented websites (American Association for the
      Study of Liver Diseases, Clinical Care Options and The Hepatitis B Foundation
      sites) offer significant, up to date information on hepatitis B for clinicians.
      Sites offering information for the public used simple patterns as fact sheets and
      question-answer sets. The majority of the sites were based in the US.
      CONCLUSIONS: Hepatitis B virus infection is adequately represented in the web,
      regarding the needs of medical practitioners. Dissemination of information for
      the public appears in various modes, and at least at present, can only safely be
      achieved through simplified reports on the disease.

PMID- 17174596
TI  - A possible parvovirus B19 encephalitis in an immunocompetent adult patient.

PMID- 17174597
TI  - Phosphatidylcholine transfer activity of yeast Sec14p is not essential for its
      function in vivo.
AB  - Yeast phosphatidylinositol (PI)/phosphatidylcholine (PC) transfer protein,
      Sec14p, is essential for protein transport from the Golgi apparatus and for the
      cell viability. It is instrumental in maintaining the lipid composition of the
      Golgi membranes to be compatible with vesicle biogenesis and the secretory
      process by coordination of PC and PI metabolism. To address the question to which
      extent PC transfer ability of Sec14p is required for its essential in vivo
      function we generated a Sec14p mutant unable to transfer PC between membranes in
      the in vitro assay. Yeast cells with this modified Sec14p(D115G) as a sole Sec14p
      were viable with improved secretory activity compared to sec14 deficient strain.
      Thus, in vitro PC transfer ability of Sec14p is not required for its essential
      function(s) in living cells, however, yeast cells having PC transfer deficient
      Sec14p(D115G) as a sole Sec14p display regulatory abnormalities, including
      increased phospholipase D mediated PC turnover.

PMID- 17174598
TI  - The recruitment order of electrically activated motor neurons investigated with a
      novel collision technique.
AB  - OBJECTIVE: The development of a novel collision technique for assessment of the
      activation order of electrically activated nerve fibers, which is an important
      question in functional electrical therapy or for interpretation of results of
      motor unit number estimates. METHODS: Compound muscle action potentials were
      recorded with the belly-tendon configuration from the abductor digiti minimi. A
      novel modified Hopf's collision technique was applied on ten healthy male
      subjects to determine the distributions of conduction velocities (DCV) of all
      ulnar nerve fibers and of the fibers activated by electrical stimuli eliciting
      20%, 50%, and 80% of the maximal muscle response. RESULTS: The maximum nerve
      conduction velocity was (means+/-SE) 64.1+/-0.85m/s. The median conduction
      velocity of estimated DCV was 58.9+/-0.97m/s (stimulus at 20%), 58.0+/-0.98m/s
      (50%), 57.2+/-0.91m/s (80%), and 56.5+/-0.84m/s (whole nerve) (all different
      between each other, P<0.001). CONCLUSIONS: The proposed collision technique
      allows the assessment of nerve conduction velocity distributions at maximal and
      sub-maximal stimulation levels and provided evidence for an inverse activation
      order of nerve fibers with electrical stimulation. SIGNIFICANCE: The excessive
      fatigue seen with nerve electrical stimulation can be explained by a preferential
      activation of large diameter nerve fibers. The motor units first activated with
      electrical stimulation are likely not representative of the motor unit pool in
      the muscle, which poses limitations in the reliability of some of the proposed
      methods for motor unit counting.

PMID- 17174599
TI  - Atrial fibrillation in heart failure patients: prevalence in daily practice and
      effect on the severity of symptoms. Data from the ALPHA study registry.
AB  - BACKGROUND: Estimates of the prevalence of atrial fibrillation (AF) in heart
      failure (HF) originate from patients enrolled in clinical trials. AIMS: To assess
      the prevalence and clinical correlates of AF among HF patients in everyday
      clinical practice from HF patients screened for the T-wave ALternans in Patients
      with Heart fAilure (ALPHA) study; to investigate the correlation between AF and
      functional status. METHODS AND RESULTS: Consecutive patients (N=3513) seen at
      nine Heart Failure Clinics were studied; 21.4% were in AF. AF prevalence was
      greater with increasing age (OR 1.04/year, p<0.001) in non-ischaemic
      cardiomyopathy (OR 2.34, p<0.001) and with increasing NYHA class (p<0.0001).
      Multiple logistic regression predictors of AF were age >70 years (OR 2.35), NYHA
      class II III or IV vs class I (OR 1.8, 4.4 and 3.1) and non-ischaemic
      cardiomyopathy (OR 3.2). A logistic model indicated that AF was associated with a
      2.5 OR of being in NYHA class III-IV vs I-II while accounting for age, gender,
      left ventricular ejection fraction (LVEF), and aetiology of HF. CONCLUSIONS: The
      prevalence of AF in HF patients exceeds 20%, and increases with age and
      functional class. The presence of AF leads to a more severe NYHA class,
      indicating that AF contributes to the severity of heart failure.

PMID- 17174600
TI  - Effects of applying a standardised management algorithm for moderate to severe
      renal dysfunction in patients with chronic stable heart failure.
AB  - BACKGROUND: No specific guidelines exist on how to manage renal dysfunction (RD)
      in patients with chronic heart failure (CHF). AIMS: To identify the proportion of
      patients with moderate to severe RD and CHF who showed an improvement in their
      renal function in response to a systematic management algorithm. METHODS: Stable
      patients with CHF and RD (defined by a serum creatinine (SCr) of >130 micromol/l
      (>1.5 mg/dl)) were enrolled into a systematic management algorithm. The following
      changes were implemented: switching aspirin to clopidogrel, halving the dose of
      both diuretics and angiotensin converting enzyme (ACE) inhibitors and switching
      between bisoprolol and carvedilol. RESULTS: Two thirds of patients in whom
      diuretics were reduced, and one fifth of patients in whom ACE inhibitors were
      reduced, improved their SCr by >25.5 micromol/l (0.3 mg/dl). All these changes
      were more marked in the presence of bilateral renal artery stenosis. Compared to
      a reference group, in whom no changes were implemented, the treatment group
      showed an improvement in their mean SCr by 35 micromol/l (0.4 mg/dl), p<0.001.
      CONCLUSION: Manipulation of pharmacological therapy for patients with CHF and RD
      results in a substantial recovery of renal function in a minority of patients.

PMID- 17174602
TI  - Reward system and addiction: what dopamine does and doesn't do.
AB  - Addictive drugs share with palatable food the property of increasing
      extracellular dopamine (DA), preferentially in the nucleus accumbens shell rather
      than in the core. However, by acting directly on the brain, drugs bypass the
      adaptive mechanisms (habituation) that constrain the responsiveness of accumbens
      shell DA to food reward, abnormally facilitating Pavlovian incentive learning and
      promoting the acquisition of abnormal DA-releasing properties by drug conditioned
      stimuli. Thus, whereas Pavlovian food conditioned stimuli release core but not
      shell DA, drug conditioned stimuli do the opposite, releasing shell but not core
      DA. This process, which results in the acquisition of excessive incentive
      motivational properties by drug conditioned stimuli, initiates the drug addiction
      process. Neuroadaptive processes related to the chronic influence of drugs on
      subcortical DA might secondarily impair the function of prefronto-striatal loops,
      resulting in impairments in impulse control and decision making that form the
      basis for the compulsive feature of drug seeking and its relapsing character.

PMID- 17174601
TI  - Urban background particulate matter and allergic sensitization in adults of ECRHS
      II.
AB  - BACKGROUND: Epidemiological studies have shown weak or inconsistent associations
      between ambient air pollutants and allergic sensitization. The aim of this study
      was to evaluate whether regional urban air pollution may partly explain the large
      variation in the prevalence of allergic sensitization across cities of the
      European Community Respiratory Health Survey (ECRHS) II. METHODS: ECRHS is a
      cross-sectional survey initiated in 29 countries across Europe in the 1990s
      (ECRHS I) with a follow-up conducted 10 years later (ECRHS II). Subject
      characteristics were measured by questionnaires and blood tests conducted for the
      measurement of specific immunoglobulin E. Fine particle mass (PM(2.5), <2.5
      microm) and sulphur on PM(2.5) were measured in 21 centres and annual averages of
      urban regional background air pollution were calculated. Results were scaled by
      an interquartile range increase in ambient PM(2.5) (6.03 microg/m(3)) and sulphur
      (1336 ng/m(3)). Generalized estimating equations were applied to compute
      population average effect estimates with adjustment for age, gender, smoking
      habit, education and number of siblings. RESULTS: A notable variation in
      pollution level and prevalence of allergic sensitization was observed. Moreover,
      exposure to urban regional background air pollution was not associated with
      allergic sensitization; adjusted odds ratios and 95% confidence interval were
      1.02 (0.95-1.09) for PM(2.5) and 1.08 (0.86-1.31) for sulphur. These
      statistically non-significant associations were sensitive to model specification.
      CONCLUSIONS: The study suggests that regional air pollution measured at fixed
      sites is not associated with allergic sensitization among adults in ECRHS II.

PMID- 17174603
TI  - In vivo neurochemical effects induced by changes in endocannabinoid
      neurotransmission.
AB  - Neurotropic effects of endo- and exo-cannabinoids are largely caused by their
      effects on classical neurotransmitter signaling. Pharmacological and molecular
      tools have been used to selectively target the endocannabinoid system.
      Endocannabinoids mostly act as retrograde messengers and, upon release from
      postsynaptic neurons, they modulate neurotransmitter release by activating
      presynaptic cannabinoid receptors. Generally, increased and decreased
      endocannabinoid neurotransmission results in decreases and increases in
      neurotransmitter release, respectively. However, net effects are often
      pleiotropic, probably owing to the level of regional endogenous tone,
      transsynaptic mechanisms and cumulative actions. Changes in classical
      neurotransmitter function can, in turn, modulate endocannabinoid signaling.
      Importantly, the endocannabinoid system can be altered in response to
      physiological and pathogenic events and targeted for therapeutic intervention.

PMID- 17174604
TI  - Diagnostic tools for filariasis elimination programs.
AB  - The ambitious and exciting Global Programme to Eliminate Lymphatic Filariasis
      (GPELF) is largely based on a strategy of mass drug administration (MDA) of
      repeated rounds of antifilarial medications to endemic populations around the
      world. Diagnostic tools are important to GPELF because they affect decisions
      regarding where to distribute MDA, how to measure its effects, how to define
      targets and endpoints for stopping MDA, and how to monitor populations for
      possible resurgence of filariasis transmission following suspension of MDA. This
      article reviews available diagnostic tests for filariasis and their potential use
      as tools for different phases of filariasis elimination programs.

PMID- 17174605
TI  - Dominant CTL-inducing epitopes on GAD65 are adjacent to or overlap with dominant
      Th-inducing epitopes.
AB  - Immune responses to GAD65 are associated with progression to T1D in NOD mice and
      humans. Our previous data suggested that dominant CTL-inducing and Th-inducing
      determinants might preferentially occur in proximal GAD65 sequences. Using a
      panel of 192 GAD65 peptides we discovered that four of the eight CTL-inducing
      peptides, including those most biologically relevant, were proximal to previously
      described I-A(g7)-restricted determinants that characterize natural islet
      autoimmunity in NOD mice. The CTL determinants 546-554 and 88-98 were presented
      by GAD65-expressing cells and were displayed on pancreatic LNC, along with 268
      278, following beta cell damage. p546-554-specific CTL were detectable in young
      naive mice and transferred significant islet inflammation into NOD.scid mice.
      These findings demonstrate that unique regions of GAD65 may be favored during
      antigen processing, such that diverse dominant epitopes are produced from
      overlapping sequences, which can engage distinct T cell subsets. Additionally,
      cross-presentation may enhance GAD65-specific CTL responses in T1D.

PMID- 17174606
TI  - Teachers' perceptions in central Turkey concerning epilepsy and asthma and the
      short-term effect of a brief education on the perception of epilepsy.
AB  - This study was aimed at assessing and comparing schoolteachers' perceptions of
      epilepsy and asthma in central Turkey. Two-hundred seventy-five schoolteachers
      completed a questionnaire on their knowledge, attitudes, and practice. There were
      18 pairs of questions on the questionnaire (one question in each pair pertained
      to epilepsy, and the other to asthma). One month later, following a brief
      education program on epilepsy, participants completed the epilepsy section of the
      questionnaire a second time. Among the teachers, initial rates of acceptance of
      children with epilepsy were significantly lower than the rates for asthma.
      Children with epilepsy were less encouraged by teachers to play with others and
      were perceived as more aggressive. More teachers were worried about other parents
      objecting to having a child with epilepsy in the class. Following the brief
      education program, there was a significant positive change in the teachers'
      perception of epilepsy.

PMID- 17174607
TI  - The seizures of Peter Alexeevich = Peter the Great, father of modern Russia.
AB  - This article deals with the seizures of Tsar Peter the Great, Father of Modern
      Russia. At the age of 10 in 1682, he witnessed the very brutal deaths of two men
      who were close to his family and the hacking of these men to pieces, directly in
      front of him. This savagery could have left scars, explaining possible
      psychogenic seizures. Also, such great quantities of alcohol were consistently
      consumed by this giant of a man at 6 ft 8 in. that alcohol withdrawal seizures
      would also seem possible. However, evidence of the latter two types of seizures
      is lacking. At the age of 21, he likely had severe encephalitis and, within that
      year, developed simple partial seizures with jerking movements of his left face
      that spread to his arm, and occasionally to his leg, finally evolving into a
      complex partial attack with loss of consciousness later. It is entirely possible
      that the seizures of Peter the Great are an example of a new entity called acute
      encephalitis with refractory, repetitive partial seizures, associated at times
      with epilepsia partialis continua and periodic lateralized epileptiform
      discharges.

PMID- 17174608
TI  - Factors associated with depressed mood in chronic pain patients: the role of
      intrapersonal coping resources.
AB  - The purpose of this study was to examine processes through which chronic pain can
      result in depressed mood and to determine whether intrapersonal coping resources,
      namely high self-esteem and optimism, affect these processes. We hypothesized
      that pain severity contributes to depressed mood largely because pain interferes
      with involvement in important pursuits. We then examined whether intrapersonal
      resources are directly associated with pain severity, interference, and depressed
      mood and whether resources moderate associations between pain and interference or
      between interference and depressed mood. Structured interviews containing
      psychometrically robust measures were conducted with 141 outpatients of a
      university hospital-affiliated chronic pain center. As predicted, interference
      mediated much of the association between pain severity and depressed mood, and
      high resources were associated with less severe pain, less interference, and
      lower depressed mood. The association between pain severity and interference was
      stronger for people with high than people with low intrapersonal resources. The
      pattern of results that emerged from this study illustrates that intrapersonal
      coping resources may affect chronic pain patients through a variety of
      differentiated mechanisms. Pain severity appears to have greater adverse impact
      on the activity of people who possess highly positive self-views and outlook, but
      these resources are also associated with better emotional status. PERSPECTIVE:
      Pain had greater adverse impact on the activity of people with highly positive
      self-views and outlook, but these coping resources were also associated with
      better emotional status. Chronic pain sufferers with few resources may require
      different interventions than those with more positive views of themselves and the
      world around them.

PMID- 17174609
TI  - Vasorelaxation induced by vascular endothelial growth factor in the human
      internal mammary artery and radial artery.
AB  - OBJECTIVES: Due to potential therapeutic value of vascular endothelial growth
      factor (VEGF) in coronary artery disease, the effect and mechanism of VEGF in
      human arteries used as coronary bypass grafts become important but not fully
      understood. VEGF-mediated endothelial regulation in vasorelaxation was studied in
      internal mammary artery (IMA) and radial artery (RA), compared with that of the
      classical agent-acetylcholine (ACh). The role of nitric oxide (NO), prostacyclin
      (PGI2), and endothelium-derived hyperpolarizing factor (EDHF) was investigated.
      METHODS: VEGF- and ACh-induced responses were measured in RA and IMA with or
      without endothelium and in the absence or presence of inhibitors of nitric oxide
      synthase or prostacyclin. In addition, the VEGF-induced PGI2 was measured by
      enzyme immunoassay. RESULTS: VEGF induced similar relaxation in RA (59.2+/-9.3%)
      and IMA (56.1+/-6.4%) that was significantly inhibited by N(omega)-nitro-L
      arginine (L-NNA) plus oxyhemoglobin (HbO) (IMA: 24.9+/-4.3%, P=0.03 vs. RA:
      25.0+/-8.6%, P=0.01) or by indomethacin (INDO) (IMA: 21.8+/-2.5%, P=0.000 vs. RA:
      30.0+/-6.6%, P=0.04) with more inhibition in IMA than RA (P<0.05). In addition,
      the VEGF-induced PGI2 was significantly higher in IMA than RA (11.5+/-2.1 vs.
      4.9+/-1.1 pg/ml/mg, P=0.002). INDO+L-NNA+HbO reduced the VEGF-induced relaxation
      to 20.8+/-4.6% in RA vs. 4.8+/-1.6% in IMA (P=0.01). In contrast, the maximal
      relaxation induced by ACh in RA (55.9+/-6.0%) and IMA (48.5+/-5.3%) was largely
      inhibited by L-NNA in IMA and RA (14.7+/-3.0%, P=0.000 vs. 15.2+/-3.2%, P=0.004)
      but little affected by INDO. CONCLUSIONS: VEGF induces similar relaxation in IMA
      and RA with significantly more PGI2-mediated relaxation and higher stimulated
      PGI2 level in IMA but more EDHF-mediated relaxation in RA. In comparison, ACh
      induced relaxation mainly depends on NO. Thus, our study reveals a significant
      difference in the mechanism of the endothelium-dependent relaxation induced by
      VEGF and ACh.

PMID- 17174610
TI  - Clinical predictors for hepatocellular carcinoma in patients with primary biliary
      cirrhosis.
AB  - BACKGROUND & AIMS: Although hepatocellular carcinoma (HCC) occurs with increased
      frequency in patients with primary biliary cirrhosis (PBC), the exact frequency
      is relatively low. Optimal selection of PBC patients for HCC screening needs to
      be determined for effective screening. In this study, we aimed to explore
      clinical predictors of HCC in PBC patients. METHODS: We performed a case-control
      study using 17 PBC patients with HCC identified from 1976 to 2002 at the Mayo
      Clinic. Control PBC patients who had no evidence of HCC were selected for each
      case by matching the first year of their visit to the Mayo Clinic. All medical
      information was collected within 2 years from when the cases were diagnosed with
      HCC. Logistic regression models were used for the analyses. RESULTS: Age, sex,
      history of blood transfusion, current smoking, histologic stage at PBC diagnosis,
      any signs of portal hypertension, Mayo score, hemoglobin level, platelet count,
      aspartate aminotransferase level, and albumin level were associated with the
      presence of HCC (P < .05 for each). In multivariable analysis, older age (OR,
      1.7; 95% confidence interval [CI], 1.1-2.5 for 5 years), male sex (OR, 9.7; 95%
      CI, 1.4-68.3), history of blood transfusion (OR, 5.0; 95% CI, 1.0-24.3), and any
      signs of portal hypertension (OR, 22.9; 95% CI, 3.4-155.3) were associated
      significantly with increased odds of HCC and yielded an excellent diagnostic
      performance (area under the receiver operating characteristics curve rate, 0.91).
      CONCLUSIONS: Older age, male sex, history of blood transfusion, and any signs of
      portal hypertension or cirrhosis indicate higher likelihood of HCC and should be
      considered for HCC screening. Further studies in larger patient cohorts are
      required to verify the diagnostic model.

PMID- 17174611
TI  - Lipid-induced colonic hypersensitivity in the irritable bowel syndrome: the role
      of bowel habit, sex, and psychologic factors.
AB  - BACKGROUND & AIMS: Duodenal lipid infusion increases colonic hypersensitivity in
      irritable bowel syndrome (IBS). Whether this is affected by bowel habit,
      psychologic factors, or sex is unknown. METHODS: We included 61 patients with IBS
      (50 women, 11 men), 25 with diarrhea-predominant IBS, 17 with constipation
      predominant IBS, 19 with alternating-type IBS, and 20 healthy controls (15 women,
      5 men). A colonic distension trial was performed with a barostat before and after
      a 1-hour duodenal lipid infusion (3 kcal/min). Colonic thresholds, colonic tone,
      and the viscerosomatic referral pattern were assessed and compared between
      groups. Patients also completed the Hospital Anxiety and Depression scale.
      RESULTS: The reduction in colonic pressure thresholds after vs before duodenal
      lipids was greater in patients than in controls for discomfort (P = .006) and
      pain (P < .0001). An increased viscerosomatic referral area for pain and
      discomfort during colonic distensions after vs before duodenal lipids was
      observed in patients but not in controls. The response was similar in IBS
      subgroups based on the predominant bowel habit, in patients with vs without
      anxiety and/or depression, and in women and men with IBS. The colonic tone
      response during lipid infusion was similar in IBS patients and controls, and in
      the different IBS subgroups. CONCLUSIONS: IBS patients show increased colonic
      sensitivity and altered viscerosomatic referral pattern after duodenal lipids.
      This response is largely unaffected by the predominant bowel habit, psychologic
      factors, or sex, but seems to be related to IBS per se.

PMID- 17174612
TI  - Effects of proton-pump inhibitors on functional dyspepsia: a meta-analysis of
      randomized placebo-controlled trials.
AB  - BACKGROUND & AIMS: The aim of this study was to assess systematically the
      efficacy of proton pump inhibitors (PPIs) in the treatment of functional
      dyspepsia compared with placebo and to determine if any difference in the
      response exists between symptom subgroups of functional dyspepsia. METHODS: A
      literature search was performed through September 2005 in PubMed, Medline,
      Embase, CINAHL, and Cochrane databases to include randomized, double-blind,
      placebo-controlled trials evaluating the efficacy of PPIs for the treatment of
      functional dyspepsia. Relative risk (RR) and relative risk reduction (RRR) and
      95% confidence intervals (CI) were calculated under a random-effects model.
      RESULTS: Seven studies with a total of 3725 patients were identified. PPIs were
      found to be more effective than placebo for reducing symptoms in patients with
      functional dyspepsia (RRR, 10.3%; 95% CI, 2.7%-17.3%). The estimated number
      needed to treat is 14.6 (95% CI, 8.7-57.1). When stratified analyses were
      performed, a significant difference in the efficacy was observed only in patients
      with ulcer-like (RRR, 12.8%; 95% CI, 7.2%-18.1%) and reflux-like dyspepsia (RRR,
      19.7%; 95% CI, 1.8%-34.3%), but not in those with dysmotility-like (RRR, 5.1%;
      95% CI, -10.9% to 18.7%) and unspecified dyspepsia (RRR, -8.0%; 95% CI, -23.7% to
      5.6%). The effect of H pylori on the efficacy of PPIs remains unclear.
      Significant heterogeneity among studies was found for the overall analysis,
      dysmotility-like dyspepsia, H pylori-negative subgroup, and different dose
      subgroups. CONCLUSIONS: PPIs are more effective than placebo for the management
      of patients with ulcer-like and reflux-like functional dyspepsia.

PMID- 17174613
TI  - Human blood plasma preparation for two-dimensional gel electrophoresis.
AB  - Human plasma consists of mainly large proteins, which vary in terms of both
      composition and concentration with the physiological state of the individual.
      Alterations in protein concentrations reflect the current state of the
      individual's health and thus may be utilized as valuable biomarkers for a
      specific biological process or disease. Two-dimensional gel electrophoresis (2
      DE) has proven to be a valuable method for the separation and comparison of
      complex protein mixtures, for example, from disease and healthy states, as this
      method provides information regarding the variation, relative quantities, and
      structures of the intact proteins. The procedures utilized for the preparation of
      samples for 2-DE are critical to the acquisition of high-quality results for the
      discovery of biomarkers. The objective of this study was to review the
      preparation methods of plasma for 2-DE, particularly those designed to improve
      the detection of proteins in low abundance in plasma on 2-DE. The use of
      anticoagulants and protease inhibitors during the collection of blood, the
      removal of abundant proteins using multicomponent immunodepletion system, and
      desalting procedure allow us to compile profiles of proteins occurring in low
      concentrations in the plasma and to improve the pattern generated during 2-DE.

PMID- 17174614
TI  - Does body weight affect wages? Evidence from Europe.
AB  - We use data from the European Community Household Panel to investigate the impact
      of body weight on wages in nine European countries. When we pool the available
      data across countries and years, we find that a 10% increase in the average body
      mass index reduces the real earnings of males and females by 3.27% and 1.86%,
      respectively. Since European culture, society and labour market are
      heterogeneous, we estimate separate regressions for Northern and Southern Europe
      and find that the negative impact of the body mass index on earnings is larger-
      and statistically significant--in the latter area.

PMID- 17174615
TI  - Interaction of rhein with human serum albumin investigation by optical
      spectroscopic technique and modeling studies.
AB  - The binding of rhein with human serum albumin (HSA) has been studied in detail by
      spectroscopic method including circular dichroism (CD), Fourier transformation
      infrared spectra (FT-IR), fluorescence spectra. The binding parameters for the
      reaction have been calculated according to Scatchard equation at different
      temperatures. The plots indicated that the binding of HSA to rhein at 303, 310
      and 318 K is characterized by one binding site with the affinity constant K at
      (4.93+/-0.16)x10(5), (4.02+/-0.16)x10(5) and (2.69+/-0.16)x10(5) M-1,
      respectively. The secondary structure compositions of free HSA and its rhein
      complexes were estimated by the FT-IR spectra. FT-IR and curve-fitted results of
      amide I band are in good agreement with the analyses of CD spectra. Molecular
      Modeling method was used to calculate the interaction modes between the drug and
      HSA.

PMID- 17174616
TI  - Evaluation of body composition in neonates and infants.
AB  - A better understanding of the nutritional needs of both healthy and sick infants
      is important. Not only does too much or too little nutrition during early life
      have long-term effects on health, but periods of rapid growth during the first
      year of life also have long-term consequences. Knowledge of the changes in body
      composition in early life can help to better define nutritional needs at these
      ages. Several methods are available for measuring body composition of neonates
      and infants. Most focus on an assessment of either body fatness or bone
      mineralization; only a few can monitor the quality of the non-fat lean tissues.
      This paper provides an evaluation of the different approaches currently available
      to monitor infant body composition, identifying both their strengths and
      limitations.

PMID- 17174617
TI  - Duplication of (12)(pter-q13.3) combined with deletion of (22)(pter-q11.2) in a
      patient with features of both chromosome aberrations.
AB  - We report a patient with multiple dysmorphic signs and congenital malformations,
      representing a combination of clinical features of duplication (12p) and deletion
      (22)(q11.2) syndromes. The girl had overgrowth at birth, showed abnormal cranio
      facial findings, cleft uvula, a complex conotruncal heart defect, a polycystic
      right kidney, and an umbilical hernia. She died at the age of 6 months of cardio
      respiratory failure. Cytogenetic examination demonstrated a derivative chromosome
      12 replacing one of the two chromosomes 22. The paternal karyotype was normal
      46,XY while the mother's karyotype was 46,XX,rcp(12;22)(q13.2;q11.2). According
      to the published data, all patients with deletion 22q11.2 combined with other
      unbalanced chromosomal aberration have a more severe clinical expression than
      those with interstitial deletions.

PMID- 17174618
TI  - Quantifying anisotropy of trabecular bone from gray-level images.
AB  - In this study, a gray-level image-based approach to quantifying structural
      anisotropy is described. The secant modulus was estimated for thirty L(3)
      vertebral bodies using nondestructive testing. The vertebral bodies were imaged
      with a clinical CT scanner. QCT measurements of BMD were also performed for
      trabecular regions. Structural anisotropy in trabecular regions was quantified
      from binarized images using the mean intercept length (MIL) method and from gray
      level images using the gray-level structure tensor (GST) method. BMD alone
      explained 28% of the variation of the secant modulus. Multivariable regression
      models combining BMD and measures of anisotropy, as proposed by the relations
      formulated by Cowin, revealed significant improvement in the prediction of the
      secant modulus. Combining a principal value of the fabric tensor, as computed by
      either MIL or GST methods, with BMD resulted in increased correlation with the
      secant modulus. The highest correlation (R(2)=0.81) was achieved with a
      combination of BMD and the third principal value of the GST. Adding a term
      proportional to the minimal cross-sectional area of the vertebral body explained
      86% of the variation of the secant modulus.

PMID- 17174619
TI  - Comparison of quantitative computed tomography-based measures in predicting
      vertebral compressive strength.
AB  - Patient-specific measures derived from quantitative computed tomography (QCT)
      scans are currently being developed as a clinical tool for vertebral strength
      prediction. QCT-based measurement techniques vary greatly in structural
      complexity and generally fall into one of three categories: (1) bone mineral
      density (BMD), (2) "mechanics of solids" (MOS) models, such as minimum axial
      rigidity (the product of axial stiffness and vertebral height), or (3) three
      dimensional finite element (FE) models. There is no clear consensus as to the
      relative performance of these measures due to differences in experimental
      protocols, sample sizes and demographics, and outcome metrics. The goal of this
      study was to directly compare the performance of QCT-based assessment techniques
      of varying degrees of structural sophistication in predicting experimental
      vertebral compressive strength. Eighty-one human thoracic vertebrae (T6-T10) from
      44 donors cadavers (F=32, M=12; 85+/-8 years old, max=97 years old, min=54 years
      old) were QCT scanned and destructively tested in uniaxial compression. The QCT
      scans were processed to generate FE models and various BMD and MOS measures,
      including trabecular bone mineral density (tBMD), integral bone mineral density
      (iBMD), and axial rigidity. Bone mineral density was weakly to moderately
      predictive of compressive strength (R(2)=0.16 and 0.62 for tBMD and iBMD,
      respectively). In vitro vertebral strength was strongly correlated with both
      axial rigidity (R(2)=0.81) and FE strength measurements (R(2)=0.80), and the
      predictive capabilities of these two metrics were statistically equivalent
      (p>0.05 for differences between FE and axial rigidity). The results of this study
      indicate that non-invasive predictive measures of vertebral strength should
      include some level of structural sophistication, specifically, gross geometric
      and material property distribution information. For uniaxial compression of
      isolated vertebrae, which is the current biomechanical testing paradigm for new
      non-invasive strength assessment techniques, QCT-based FE and axial rigidity
      measures are equivalent predictors of experimental strength. However, before
      abandoning the FE method in favor of more simplistic techniques, future work
      should investigate the performance of the FE method versus MOS measures for more
      physiologically representative loading conditions, e.g., anterior bending or in
      situ loading with intervertebral discs intact.

PMID- 17174620
TI  - Evaluation of bioreactor-cultivated bone by magnetic resonance microscopy and
      FTIR microspectroscopy.
AB  - We present a three-dimensional mineralizing model based on a hollow fiber
      bioreactor (HFBR) inoculated with primary osteoblasts isolated from embryonic
      chick calvaria. Using non-invasive magnetic resonance microscopy (MRM), the
      growth and development of the mineralized tissue around the individual fibers
      were monitored over a period of 9 weeks. Spatial maps of the water proton MRM
      properties of the intact tissue, with 78 microm resolution, were used to
      determine changes in tissue composition with development. Unique changes in the
      mineral and collagen content of the tissue were detected with high specificity by
      proton density (PD) and magnetization transfer ratio (MTR) maps, respectively. At
      the end of the growth period, the presence of a bone-like tissue was verified by
      histology and the formation of poorly crystalline apatite was verified by
      selected area electron diffraction and electron probe X-ray microanalysis. FTIR
      microspectroscopy confirmed the heterogeneous nature of the bone-like tissue
      formed. FTIR-derived phosphate maps confirmed that those locations with the
      lowest PD values contained the most mineral, and FTIR-derived collagen maps
      confirmed that bright pixels on MTR maps corresponded to regions of high collagen
      content. In conclusion, the spatial mapping of tissue constituents by FTIR
      microspectroscopy corroborated the findings of non-invasive MRM measurements and
      supported the role of MRM in monitoring the bone formation process in vitro.

PMID- 17174621
TI  - Ibandronate treatment reverses glucocorticoid-induced loss of bone mineral
      density and strength in minipigs.
AB  - The Gottingen minipig is one of the few large animal models that show
      glucocorticoid (GC)-induced bone loss. We investigated whether GC-induced loss of
      bone mineral density (BMD) and bone strength in minipigs can be recovered by
      treatment with the bisphosphonate ibandronate (IBN). 40 primiparous sows were
      allocated to 4 groups when they were 30 months old: GC treatment for 8 months
      (GC8), for 15 months (GC15), GC treatment for 15 months plus IBN treatment for
      months 8-15 (GC&IBN), and a control group without GC treatment. Prednisolone was
      given at a daily oral dose of 1 mg/kg body weight for 8 weeks and thereafter 0.5
      mg/kg body weight. IBN was administered intramuscularly and intermittently with
      an integral dose of 2.0 mg/kg body weight. BMD of the lumbar spine (L1-3) was
      assessed in vivo by Quantitative Computed Tomography (QCT) at months 0, 8, and
      15. Blood and urine samples were obtained every 2-3 months. After sacrificing the
      animals lumbar vertebrae L4 were tested mechanically (Young's modulus and
      ultimate stress). Histomorphometry was performed on L2 and mineral content
      determined in ashed specimens of T12 and L4. In the GC&IBN group, the GC
      associated losses in BMD of -10.5%+/-1.9% (mean+/-standard error of the mean,
      p<0.001) during the first 8 months were more than recovered during the following
      7 months of IBN treatment (+14.8%+/-1.2%, p<0.0001). This increase was
      significantly larger (p<0.0001) than the insignificant +2.1%+/-1.2% change in
      group GC15. At month 15, the difference between groups GC&IBN and GC15 was 22%
      (p<0.01) for BMD, 48% (p<0.05) for Young's modulus, and 31% (p<0.14) for ultimate
      stress; bone-specific alkaline phosphatase showed trends to lower values (p<0.2)
      while deoxypyridinoline was comparable. This minipig study demonstrates that GC
      induced impairment of bone strength can be effectively and consistently treated
      by IBN. GC&IBN associated alterations in BMD and bone turnover markers can be
      monitored in vivo using QCT of the spine and by biochemical analyses, reflecting
      the changes in bone strength.

PMID- 17174623
TI  - Meta-analysis of diagnostic tests should include estimates for both sensitivity
      and specificity.

PMID- 17174622
TI  - Association of the methylenetetrahydrofolate reductase C677T polymorphism and
      fracture risk in Chinese postmenopausal women.
AB  - Osteoporotic fractures are a leading cause of disability and, indirectly, of
      death in the elderly population. Previous studies have shown that homocysteine
      level and the C677T polymorphism in the gene encoding methylenetetrahydrofolate
      reductase (MTHFR) may be involved in the development of osteoporosis and its
      related fracture in European populations. The aim of this study was to verify the
      association of this polymorphism with bone mineral density (BMD) and fractures in
      our 1899 Chinese postmenopausal women. The C677T T allele frequency in this
      population was 39.2%. The distribution of the MTHFR genotypes followed the Hardy
      Weinberg equilibrium. BMD at total body, total hip or femoral neck did not
      significantly vary with MTHFR C677T genotype. The T allele carrier tended to have
      higher risk of having osteoporosis or osteopenia, but the difference was
      statistically insignificant. However, Poisson regression analysis revealed that
      the T allele carriers had an increased risk of fractures (RR=1.7, 95% CI=1.1-2.7,
      p=0.01) which occurred before or after menopause. As far as fracture incidence
      after menopause was concerned, the CT or TT genotype had more than twice the risk
      of the CC genotype (RR=2.5, 95% CI=1.2-4.9, p=0.009). This association was
      independent of age, physical activity, occupation, passive smoking, height,
      weight, years since menopause, and total hip BMD. Our data show that the MTHFR
      C677T polymorphism is an independent predictor of fracture risk, although it only
      had a weak effect on BMD. Further study on the mechanistic role that this
      polymorphism plays in the development of fractures may lead to better
      understanding of the etiology of osteoporotic fracture.

PMID- 17174625
TI  - Improving outpatient care in chronic cardiac diseases: no easy solutions.

PMID- 17174626
TI  - Complementarity and competitiveness of the intrinsic and extrinsic components of
      the total ventricular load: demonstration after valve replacement in aortic
      stenosis.

PMID- 17174627
TI  - Pacing Evaluation-Atrial SUpport Study in Cardiac Resynchronization Therapy
      (PEGASUS CRT): design and rationale.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been demonstrated to be
      an effective heart failure (HF) therapy. All pivotal trials of CRT to date have
      used atrial-synchronous biventricular pacing wherein there is no or minimal
      atrial pacing. In clinical practice, however, physicians often program CRT
      devices to have atrial rate support pacing, either by increasing the lower rate
      limit or by activating the rate sensor. OBJECTIVE: The purpose of this study is
      to evaluate the effect of empiric atrial support pacing in patients with HF who
      have received a CRT defibrillator (CRT-D) device. METHODS: PEGASUS CRT is a
      multicenter, 3-arm, randomized clinical trial of approximately 1200 patients
      receiving a CRT-D device. For the first 6 weeks after implant, devices are
      programmed to DDD with a lower rate limit of 40 beats/min. At 6 weeks, patients
      are randomized to DDD-40, DDD-70, or DDDR-40. All randomized patients are
      followed for 1 year, and at each visit, mortality, HF events, quality of life,
      New York Heart Association class, and atrial and ventricular arrhythmic episodes
      are evaluated. An exercise substudy will also be conducted, enrolling a minimum
      of 375 patients. Patients in this substudy will complete 2 cardiopulmonary
      exercise tests to evaluate the effect pacing mode has on exercise capacity. This
      randomized controlled trial will address whether empiric atrial support pacing is
      of clinical benefit to patients with HF who receive a CRT-D device.

PMID- 17174628
TI  - MISSION!: optimization of acute and chronic care for patients with acute
      myocardial infarction.
AB  - BACKGROUND: Guideline implementation programs for patients with acute myocardial
      infarction (AMI) enhance adherence to evidence-based medicine (EBM) and improve
      clinical outcome. Although undertreatment of patients with AMI is well recognized
      in both acute and chronic phases of care, most implementation programs focus on
      acute and secondary prevention strategies during the index hospitalization phase
      only. HYPOTHESIS: Implementation of an all-phase integrated AMI care program
      maximizes EBM in daily practice and improves the care for patients with AMI. AIM:
      The objective of this study is to assess the effects of the MISSION! program on
      adherence to EBM for patients with AMI by the use of performance indicators.
      DESIGN: The MISSION! protocol is based on the most recent American College of
      Cardiology/American Heart Association and European Society of Cardiology
      guidelines for patients with AMI. It contains a prehospital, inhospital, and
      outpatient clinical framework for decision making and treatment, up to 1 year
      after the index event. MISSION! concentrates on rapid AMI diagnosis and early
      reperfusion, followed by active lifestyle improvement and structured medical
      therapy. Because MISSION! covers both acute and chronic AMI phase, this design
      implies an intensive multidisciplinary collaboration among all regional health
      care providers. CONCLUSION: Continuum of care for patients with AMI is warranted
      to take full advantage of EBM in day-to-day practice. This manuscript describes
      the rationale, design, and preliminary results of MISSION!, an all-phase
      integrated AMI care program.

PMID- 17174629
TI  - Incidence, predictors, and outcomes of device failure of X-sizer thrombectomy:
      real-world experience of 200 cases in 5 years.
AB  - BACKGROUND: Clinical studies have evaluated the safety and efficacy of adjunctive
      X-sizer (EndiCOR Inc, San Clemente, CA) in percutaneous coronary intervention
      (PCI). However, patient and lesion subsets were highly selected, and
      extrapolation of the results to daily practice is problematic. METHODS: X-sizer
      thrombectomy was performed in 200 procedures from August 2000 to July 2005. The
      indications for the procedures were primary PCI in 71%. Device failure was
      defined as the occurrence of 1 or more of the following conditions: (a) failure
      of the X-sizer to reach the target segment, (b) failure to achieve final
      thrombolysis in myocardial infarction 3 flow, (c) slow flow or no-reflow, (d)
      distal embolization, and (e) coronary perforation. RESULTS: Device failure
      occurred in 48 procedures, giving a device failure rate of 24%. Logistic
      regression analysis showed that ostial lesion was the only independent predictor
      of device failure (OR 4.89, 95% CI 1.23-19.51, P = .024). A total of 19 patients
      had developed 22 adverse events, giving a 30-day adverse event rate of 9.5%.
      Among these, there were 13 deaths, 4 strokes, 2 reinfarctions, 2 repeat PCIs, and
      1 coronary artery bypass grafting. Logistic regression analysis showed that X
      sizer device failure was independently associated with 30-day adverse events (OR
      3.42, 95% CI 1.04-11.25, P = .043). CONCLUSIONS: The incidence of device failure
      of X-sizer thrombectomy was 24%. Ostial lesion was an independent predictor of
      device failure. Notably, X-sizer device failure was independently associated with
      30-day adverse event. These highlight the importance of case selection and the
      problem with its use in ostial lesions.

PMID- 17174630
TI  - Drug-eluting stents for the treatment of bifurcation lesions: a randomized
      comparison between paclitaxel and sirolimus stents.
AB  - BACKGROUND: Drug-eluting stents have been shown to reduce restenosis in many
      types of lesions. The purpose of this article is to assess the efficacy of
      sirolimus- and paclitaxel-eluting stents in patients with bifurcation lesions.
      METHODS: Between June 2003 and October 2004, 205 patients were enrolled in a
      prospective randomized trial; 103 patients were assigned to sirolimus stents and
      102 patients to paclitaxel stents. All patients were treated by provisional T
      stenting. RESULTS: There were no differences between groups in terms of age, risk
      factors, clinical condition, location of the bifurcation lesion, or other
      technical factors. Angiographic data and immediate results were also similar in
      both groups. Three patients developed inhospital non-Q-wave acute myocardial
      infarction (2 from the sirolimus group and 1 from the paclitaxel group). Follow
      up angiography was obtained in 109 patients (53%). In the sirolimus group, 5
      patients developed restenosis (9%): 1 at the main vessel, 2 at the side branch,
      and 2 in both branches. In contrast, 16 patients from the paclitaxel group had
      restenosis (29%): 6 at the main vessel, 5 at the side branch, and 5 in both
      branches. Target lesion revascularization at 24 +/- 5 months post stenting
      occurred in 4 patients from the sirolimus group (4%) and in 13 from the
      paclitaxel group (13%) (P < .05). Late loss at the main vessel in the sirolimus
      group patients was 0.31 +/- 0.59 versus 0.60 +/- 0.77 mm in patients from the
      paclitaxel group (P < .05). CONCLUSIONS: Patients with bifurcation lesions
      treated by sirolimus showed significantly lower rates of late loss, restenosis
      and target lesion revascularization than patients treated with paclitaxel-eluting
      stents.

PMID- 17174631
TI  - A quality guarantee in acute coronary syndromes: the American College of
      Cardiology's Guidelines Applied in Practice program taken real-time.
AB  - BACKGROUND: Wide variation exists in the management of acute coronary syndromes
      (ACSs), which includes an apparent underutilization of evidence-based therapies.
      We have previously demonstrated that application of the American College of
      Cardiology Guidelines Applied in Practice (GAP) tools can improve quality
      indicator rates and outcomes of patients hospitalized with ACS. OBJECTIVE: To
      determine whether a real-time system for monitoring key quality-of-care
      indicators using GAP would improve both process indicators and outcomes beyond
      those of the initial implementation of GAP. DESIGN: Prospective patient
      identification, prospective chart coding, retrospective data abstraction.
      PATIENTS: All patients with ACS admitted (N = 3189) to our institution between
      January 1, 1999, and December 2004; 2019 studied before real-time implementation
      from January 1, 1999, to June 30, 2002, and 1170 studied during real-time
      implementation from July 1, 2002, to December 31, 2004. MAIN OUTCOME MEASURE: The
      effect of real-time monitoring of key quality indicators on inhospital therapy
      and outcomes, and 6-month outcomes in patients admitted with ACS. RESULTS: The
      real-time GAP implementation correlated with more frequent use of inhospital
      angiotensin-converting enzyme inhibitors (72.7% vs 63.7%, P < .0001), beta
      blockers (93.0% vs 89.7%, P = .0016), statins (81.2% vs 65.9%, P < .0001),
      antiplatelet agents (69.2% vs 22.5%, P < .0001), and glycoprotein IIb/IIIa
      inhibitors (35.5% vs 26.7%, P < .0001). There were fewer episodes of inhospital
      congestive heart failure (3.85% vs 8.77%, P < .0001) and major bleeding events
      (3.2% vs 7.9%, P < .0001) after the real-time system was adopted. Real-time GAP
      also resulted in higher discharge rates of aspirin (92.1% vs 86.5%, P < .0001),
      beta blockers (86.8% vs 79.1%, P < .0001), statins (81.2% vs 64.7%, P < .0001),
      and angiotensin-converting enzyme inhibitors (67.1% vs 55.5%, P < .0001). Real
      time GAP implementation was associated with fewer rehospitalizations for heart
      disease (19.8% vs 25.2%, P = .0014), myocardial infarction (3.5% vs 5.4%, P =
      .0243), and combined death/cerebrovascular accident/myocardial infarction (9.5%
      vs 13.9%, P = .0009) during the first 6 months after discharge. CONCLUSION: The
      institution of a formal system to review and "guarantee" key quality-of-care
      indicators real time in the hospital is associated with improved outcomes in
      patients admitted with ACS. The combination of American College of Cardiology's
      GAP program and its real-time implementation leads to higher use of evidence
      based therapies and correspondingly better outcomes than those associated with
      the initial GAP implementation.

PMID- 17174632
TI  - Impact of opinion leader-endorsed evidence summaries on the quality of
      prescribing for patients with cardiovascular disease: a randomized controlled
      trial.
AB  - BACKGROUND: Local opinion leaders are educationally and socially influential
      physicians. Although they can accelerate the adoption of new evidence in
      hospitals, their impact on the quality of prescribing for outpatients has only
      been examined by a few studies. We hypothesized that an intervention consisting
      of patient-specific one-page evidence summaries, generated and endorsed by local
      opinion leaders, would improve prescribing of angiotensin-converting enzyme (ACE)
      inhibitors or angiotensin receptor blockers (ARBs) in heart failure (HF) and that
      of statins in ischemic heart disease (IHD). METHODS: We conducted a community
      based randomized controlled trial in patients with HF (not receiving ACE
      inhibitors or ARBs) and those with IHD (not receiving statins) who were recruited
      from 40 pharmacies and allocated either to the opinion leader intervention or to
      usual care based on randomization of their primary care physician. The primary
      outcome was an increase in the use of efficacious therapies (ACE inhibitors or
      ARBs in HF and statins in IHD) within 6 months; the secondary outcomes were
      prescribing changes for HF or IHD. RESULTS: A total of 171 patients participated
      in the study; 87 were allocated to the intervention, whereas 84 were assigned to
      the control group. The median age of the participants was 75 years; 103 (60%)
      were female, 54 (32%) had HF, and 117 (68%) had IHD. Overall, 21 (24%)
      intervention patients started receiving an efficacious medication within 6
      months, as compared with 15 (18%) control subjects (relative risk of improvement
      1.32, 95% CI 0.73-2.40, P = .31). In the HF subgroup, 38% of the intervention
      patients started receiving an ACE inhibitor or ARB therapy, as compared with 20%
      of control subjects (relative risk of improvement 1.90, 95% CI 0.76-4.72, P =
      .15). In the IHD subgroup, 17% of the intervention patients and 17% of the
      control subjects started receiving statin therapy (P = .97). CONCLUSIONS: The
      influence of local opinion leaders may be useful for improving the quality of
      cardiovascular prescribing in the community, but the benefits are likely modest
      and may be disease specific. Further studies on this method are warranted.

PMID- 17174633
TI  - Global Registry of Acute Coronary Events (GRACE) hospital discharge risk score
      accurately predicts long-term mortality post acute coronary syndrome.
AB  - BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) hospital
      discharge risk score (GRACE score) developed from a multinational registry
      involving all subsets of acute coronary syndrome (ACS) predicted 6-month
      survival. There is currently no validated risk model to predict mortality beyond
      6 months. METHODS AND RESULTS: Of the 1143 consecutive patients with ACS admitted
      to coronary care unit in 2000 to 2002 (mean age, 64.9 +/- 12.6 years), 39% had ST
      elevation myocardial infarction, 39% had non-ST-elevation infarction, and 22% had
      unstable angina. The mortality was 7.5% during index admission, 12.1% at 6
      months, 14.8% at 1 year, 18.7% at 2 years, 25.0% at 3 years, and 39.2% at 4
      years. The GRACE hospital discharge risk score calculated for 1057 hospital
      survivors discriminated survival from death at 6 months (C index, 0.81), 1 year
      (C index, 0.82), 2 years (C index, 0.81), 3 years (C index, 0.81), and 4 years (C
      index, 0.80). The risk score worked for all 3 subsets of ACS at all time points,
      with C index >0.75 in all analyses. A separate multivariable mortality model for
      these 1057 patients over the 4-years follow-up period identified 10 independent
      predictors of mortality. Seven were in the GRACE risk model (age, history of
      ischemic heart disease, heart failure, increased heart rate on admission, serum
      creatinine level, evidence of myonecrosis, not receiving in-hospital percutaneous
      coronary intervention). CONCLUSIONS: The GRACE postdischarge risk score contains
      relevant prognostic factors and accurately discriminate survivors from
      nonsurvivors over the longer term (up to 4 years) in all subsets of ACS patients.

PMID- 17174634
TI  - Risk stratification for patients undergoing nonurgent percutaneous coronary
      intervention using N-terminal pro-B-type natriuretic peptide: a Clopidogrel for
      the Reduction of Events During Observation (CREDO) substudy.
AB  - BACKGROUND: The utility of N-terminal pro-BNP (NT-proBNP) measurement as a
      prognostic marker during nonurgent percutaneous coronary intervention (PCI) has
      been suggested in several studies. The comparative prognostic values between NT
      proBNP levels and left ventricular ejection fraction (LVEF) in the nonurgent PCI
      setting are unclear. METHODS: CREDO was a double blind, placebo-controlled,
      randomized trial comparing 2 clopidogrel regimens before and after nonurgent PCI.
      Baseline NT-proBNP levels and LVEF were measured in 1468 subjects using the Roche
      Elecsys proBNP assay (Roche Diagnostics, Indianapolis, IN), and the 1-year
      combined end point of death/myocardial infarction (MI)/stroke was analyzed
      according to NT-proBNP quartiles in impaired and preserved LVEF. RESULTS: In this
      patient cohort (mean age 61.6 +/- 10 years, 22% with LVEF < 50%), the median NT
      proBNP level was 131 pg/mL. Increasing quartiles of NT-proBNP were associated
      with a higher rate of death, MI, and the combined end point (but not stroke) at 1
      year, including those with LVEF > or = 50% (P < .001 for trend). This prognostic
      power for death and MI remained robust even when adjusted for other clinical or
      biochemical markers including cardiac troponin, creatinine clearance, and high
      sensitive C-reactive protein (hazard ratio 1.249, P = .006). Despite its robust
      prognostic value, baseline NT-proBNP levels did not identify patients with
      enhanced benefit from pre-procedural and prolonged clopidogrel therapy.
      CONCLUSIONS: In patients undergoing a nonurgent PCI, NT-proBNP levels may provide
      important prognostic value for death and MI, even in patients with preserved
      cardiac function, However, NT-proBNP levels were unable to identify patients with
      enhanced benefit from pre-procedural and prolonged clopidogrel therapy.

PMID- 17174635
TI  - Platelet reactivity in patients with subacute stent thrombosis compared with non
      stent-related acute myocardial infarction.
AB  - BACKGROUND: Recent case control studies suggest that patients with subacute stent
      thrombosis (SAT) have increased platelet reactivity. However, SAT often presents
      as acute myocardial infarction (AMI), which is also associated with augmented
      platelet activation. We therefore compared platelet reactivity in patients with
      SAT and patients with AMI unrelated to stenting. METHODS: We identified 20
      patients with SAT, 20 patients with ST-elevation AMI who underwent primary
      percutaneous coronary intervention (PCI), and 20 patients who underwent stenting
      without SAT occurrence (stable control group). Platelet function was measured >
      or = 3 days after PCI in the SAT (repeat procedure) and AMI groups and > or = 3
      months after stenting in the stable group. All patients received aspirin and
      clopidogrel. Platelet reactivity was evaluated by aggregation in response to 5
      and 20 micromol/L of adenosine diphosphate and 1.5 mmol/L arachidonic acid, and
      by flow cytometric determination of P-selectin and glycoprotein IIb/IIIa
      activation. RESULTS: Clinical characteristics were similar among the groups.
      Platelet testing was performed 4.9 +/- 1.7, 3.1 +/- 0.3, and 108 +/- 22 days
      after PCI in the SAT, AMI, and stable groups, respectively. The SAT group had
      higher platelet aggregation and activation markers than the stable group.
      However, platelet aggregation and activation was very similar in the SAT and AMI
      groups. CONCLUSIONS: Patients with SAT have increased platelet reactivity,
      compared with patients who do not develop SAT following stenting. However, the
      augmented platelet reactivity does not appear to differ from patients with AMI
      unrelated to stenting. This study highlights the need for large prospective
      studies to determine whether platelet hyperreactivity increases the risk of SAT.

PMID- 17174636
TI  - The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT) Heart Failure Validation Study: diagnosis and prognosis.
AB  - BACKGROUND: ALLHAT, a randomized, double-blind, active-controlled hypertension
      treatment trial in 42,418 patients, reported that a thiazide-type diuretic
      (chlorthalidone) was superior to a calcium channel blocker (amlodipine), an
      angiotensin-converting enzyme inhibitor (lisinopril), and an alpha1-blocker
      (doxazosin) in preventing the new onset of heart failure (HF). However, questions
      have been raised regarding the validity of the HF diagnosis. METHODS: The ALLHAT
      HF Validation Study was designed to validate and elucidate the significance of HF
      events in ALLHAT. Records for 2778 HF hospitalizations in 1935 patients were
      centrally reviewed using several prespecified algorithms (based on ALLHAT and
      Framingham criteria) and reviewers' global clinical judgment. Percent agreement
      with diagnoses assigned by ALLHAT site physicians, relative risks across
      randomized comparisons, incidence rates, and mortality after HF hospitalization
      were evaluated for first events validated by each of the criteria sets. RESULTS:
      Percent agreements with site physician diagnoses were 71%, 80%, and 84% for
      ALLHAT, Framingham, and reviewers' judgment, respectively. Using these 3
      criteria, relative risks (95% CI) for new-onset HF compared with chlorthalidone
      were, respectively, 1.46 (1.27-1.68), 1.42 (1.25-1.62), and 1.45 (1.28-1.64) for
      amlodipine; 1.18 (1.02-1.28), 1.13 (0.99-1.30), and 1.15 (1.01-1.32) for
      lisinopril; and 1.79 (1.51-2.11), 1.71 (1.46-2.00), and 1.80 (1.55-2.10) for
      doxazosin. CONCLUSIONS: An independent review of source documentation showed a
      high degree of agreement with the HF diagnoses assigned by site physicians and
      confirmed the higher risk of HF associated with first-step therapy using
      amlodipine, lisinopril, or doxazosin compared with chlorthalidone. Thiazide-type
      diuretics should be the preferred first-step therapy for prevention of HF in high
      risk patients with hypertension.

PMID- 17174637
TI  - Absence of an interaction between the angiotensin-converting enzyme insertion
      deletion polymorphism and pravastatin on cardiovascular disease in high-risk
      hypertensive patients: the Genetics of Hypertension-Associated Treatment (GenHAT)
      study.
AB  - BACKGROUND: The aim of this study was to determine whether the angiotensin
      converting enzyme (ACE) insertion-deletion (ID) polymorphism interacts with
      pravastatin to modify the risk of coronary heart disease (CHD) and other
      cardiovascular end points in a large clinical trial. METHODS: GenHAT is an
      ancillary study of the ALLHAT. The ACE ID genotyped population in the lipid
      lowering arm of ALLHAT included 9467 participants randomly assigned to
      pravastatin (n = 4741) or to usual care (n = 4726). The efficacy of pravastatin
      in reducing the risk of primary outcome (all-cause mortality) and secondary
      outcomes (fatal CHD and nonfatal myocardial infarction, cardiovascular disease
      [CVD] mortality, CHD, stroke, other CVD, non-CVD mortality, stroke, and heart
      failure) was compared between the genotype strata (dominant model ID + II vs DD,
      additive model II vs ID vs DD), by examining an interaction term in a Cox
      proportional hazards model. RESULTS: The relative risk of fatal CHD and nonfatal
      myocardial infarction among subjects randomized to pravastatin compared with
      subjects randomized to usual care was similar in subjects with the II genotype
      (hazard ratio [HR] 0.84, 95% CI 0.59-1.18), the ID genotype (HR 0.84, 95% CI 0.68
      1.03), and the DD genotype (HR 0.99, 95% CI 0.77-1.27). CONCLUSIONS: We found no
      evidence that the ACE ID genotype was a major modifier of the efficacy of
      pravastatin in reducing the risk of cardiovascular events.

PMID- 17174638
TI  - Comparison of measures of medication persistency using a prescription drug
      database.
AB  - PURPOSE: Studies of medication persistency using drug databases use different
      definitions of persistency, making it difficult to compare the results from
      separate studies. We undertook a study of persistency to statins using various
      definitions to compare the results obtained with the different definitions.
      METHODS: All patients with an acute myocardial infarction in the province of
      Quebec between April 1999 and March 2004 who filled a prescription for a statin
      within 30 days of discharge were identified. The main outcomes were the 1-year
      rates of persistency defined as (1) the proportion of individuals with a
      medication possession ratio > or = 80%, (2) the proportion of individuals having
      filled a prescription in the last 60 days of the year, and (3) the proportion of
      individuals with continuous exposure after the initial prescription, using a
      grace period of 7 days or 25% of the duration of the previous prescription
      between successive prescriptions. Kaplan-Meier analysis was also performed to
      assess continuous persistency over time using a 7-day grace period. RESULTS: Of
      the 20,239 patients identified, 1 year persistency to statins ranged from 41% to
      90%, depending on the definition used: 85% had a medication possession ratio for
      statins > or = 80%, 90% filled a prescription in the last 60 days of the year,
      41% to 44% had continuous persistency, and, in survival analysis, the probability
      of continuous persistency was 41%. CONCLUSIONS: Measures of medication
      persistency yield different results, depending on the definition used to define
      persistency. Results of studies of persistency should thus be interpreted with
      caution.

PMID- 17174639
TI  - Antiplatelet therapy and progression of coronary artery disease: a placebo
      controlled trial with angiographic and clinical follow-up after myocardial
      infarction.
AB  - INTRODUCTION: In patients after ST-elevation myocardial infarction (STEMI),
      antiplatelet therapy reduces subsequent cardiac events, which are often
      attributed to recurrent thrombosis with (sub)total occlusion in the infarct
      related artery. Whether antiplatelet therapy influences the often subclinical
      process of coronary disease progression in noninfarct arteries has not been
      reported. METHODS: Quantitative coronary angiography of noninfarct arteries was
      performed on paired cine-angiograms of 149 patients from fibrinolytic trials who
      had a patent infarct-related artery 3 to 4 weeks following STEMI and who were
      randomized to either continue the daily combination of 50-mg aspirin and 400-mg
      dipyridamole or to matching placebo. Follow-up angiography was scheduled at 1
      year. RESULTS: On a per-patient basis, the change in minimal luminal diameter
      (MLD) was 0.00 mm in the aspirin/dipyridamole group (n = 76) and was 0.01 mm in
      the placebo group (n = 73). There was no difference between these groups in the
      changes in MLD (-0.02 mm; 95% CI -0.09 to 0.05), neither were there significant
      differences in mean luminal diameter and diameter stenosis. Progression (1
      segment/patient with > or = 0.40 mm decrease in MLD) was seen in two thirds of
      patients and did not independently predict long-term death and/or reinfarction.
      CONCLUSION: In this placebo-controlled trial after STEMI, the combination of
      aspirin and dipyridamole did not affect noninfarct artery disease progression.
      Progression did not predict long-term clinical outcome.

PMID- 17174640
TI  - A comparison of prasugrel and clopidogrel loading doses on platelet function:
      magnitude of platelet inhibition is related to active metabolite formation.
AB  - BACKGROUND: The aim of this study was to compare rate of onset, magnitude, and
      consistency of platelet inhibition after administration of prasugrel or
      clopidogrel and to relate platelet inhibition to systemic exposure to each active
      metabolite. Thienopyridines are prodrugs, metabolized in vivo to active
      metabolites that inhibit the platelet P2Y12 adenosine diphosphate (ADP) receptor.
      METHODS: This was an open-label, 2-way, crossover study that randomized healthy
      subjects (n = 68) to an oral loading dose (LD) of prasugrel 60 mg or clopidogrel
      300 mg. Platelet aggregation response to 5 and 20 micromol/L of ADP was measured
      by turbidometric aggregometry. Plasma concentrations of the active metabolites of
      prasugrel and clopidogrel were quantified by liquid chromatography with tandem
      mass spectrometry detection methods. RESULTS: Inhibition of platelet aggregation
      (IPA) after prasugrel was significantly higher (P < .01) than that after
      clopidogrel from 15 minutes through 24 hours (5 micromol/L ADP) and from 30
      minutes through 24 hours (20 micromol/L ADP). For 20 micromol/L ADP, the median
      time to reach > or = 20% IPA was 30 minutes for prasugrel and 1.5 hours for
      clopidogrel (P < .001). The maximum IPA was 84.1% +/- 9.5% with prasugrel versus
      48.9% +/- 27.0% with clopidogrel for 5 micromol/L ADP and 78.8% +/- 9.2% versus
      35.0% +/- 24.5%, respectively, for 20 micromol/L ADP (P < .001). Response to
      prasugrel was more consistent compared to clopidogrel (P < .01). The lower IPA
      response to clopidogrel was associated with lower plasma concentrations of its
      active metabolite (P < .001). CONCLUSIONS: Prasugrel 60 mg LD results in more
      rapid, potent, and consistent inhibition of platelet function than clopidogrel
      300 mg LD. Lower IPA responses to clopidogrel were associated with lower
      concentrations of its active metabolite.

PMID- 17174641
TI  - Asymmetric dimethylarginine, cortisol/cortisone ratio, and C-peptide: markers for
      diabetes and cardiovascular risk?
AB  - BACKGROUND: Diabetes and prediabetic conditions are growing cardiovascular risk
      factors. Better understanding and earlier recognition and treatment of
      dysglycemia-related risk are health priorities. We assessed the predictive value
      of 3 proposed new markers for diabetes and cardiovascular risk. We tested whether
      the plasma levels of (1) asymmetric dimethylarginine (ADMA), (2)
      cortisol/cortisone (Cl/Cn) ratio, and (3) C-peptide predicted glycemic status,
      coronary artery disease, and death or myocardial infarction (MI) in a nested case
      control cohort (N = 850) with normal fasting glucose (< 110 mg/dL), impaired
      fasting glucose (110-125), or diabetic (> or = 126) status. METHODS: High
      sensitivity C-reactive protein (hsCRP) served as a control risk marker. Follow-up
      averaged 2.6 +/- 1.4 years. High-pressure liquid chromatography with pre-column
      derivitization and fluorescence was used to assay ADMA, liquid
      chromatography/tandem mass spectrometry for Cl and Cn, and chemiluminescent
      immunoassay for C-peptide. RESULTS: Asymmetric dimethylarginine levels were
      positively associated with glycemic category (P < .001). Quartiles 2 to 4 ADMA
      also conferred increased risk of death/MI independent of hsCRP and other risk
      factors (adjusted hazard ratio, 2.1; P = .002). Cortisol/Cortisone ratios (P =
      .013) and C-peptide (P = .047) were associated with glycemic categories but less
      strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident
      death/MI (adjusted hazard ratio, 0.48; P < .001), whereas C-peptide did not
      predict outcomes. CONCLUSIONS: Among a high coronary risk case-control cohort,
      ADMA (strongly), Cl/Cn (moderately), and C-peptide (weakly) predicted glycemic
      categories. Asymmetric dimethylarginine and Cl/Cn also predicted clinical outcome
      independent of and more strongly than hsCRP. Asymmetric dimethylarginine and
      Cl/Cn represent promising new candidate markers of dysglycemia and associated
      cardiovascular risk.

PMID- 17174643
TI  - Carvedilol use at discharge in patients hospitalized for heart failure is
      associated with improved survival: an analysis from Organized Program to Initiate
      Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF).
AB  - BACKGROUND: The IMPACT-HF trial demonstrated that carvedilol use at the time of
      heart failure (HF) hospital discharge significantly increased 90-day
      postdischarge treatment rates. Whether there is an early survival benefit
      associated with this therapeutic approach in patients hospitalized for HF is
      unknown. We examined the early effects on mortality and rehospitalization of
      carvedilol use at discharge in patients hospitalized for HF and left ventricular
      systolic dysfunction (LVSD) compared with outcomes in patients who are eligible
      for, but do not receive, beta blockers before discharge. METHODS: The OPTIMIZE-HF
      program enrolled 5791 patients admitted with HF in a web-based registry at 91
      hospitals participating with prespecified 60- to 90-day follow-up from March 2003
      to December 2004. Outcomes data were prospectively collected on patients eligible
      for beta-blocker therapy and analyzed according to predischarge beta-blocker use.
      RESULTS: The mean age was 69.7 years; 63% were male, etiology was ischemic in
      52%, and mean left ventricular ejection fraction was 24.3%. A total of 2720
      patients had LVSD, among whom 2373 (87.2%) were eligible to receive a beta
      blocker at discharge and carvedilol was prescribed in 1162 (49.0%). Discharge use
      of carvedilol was associated with a significant reduction in mortality risk at 60
      to 90 days (hazard ratio 0.46, P = .0006) and mortality or rehospitalization
      (odds ratio 0.71, P = .0175) compared to no predischarge beta blocker.
      Predischarge use of carvedilol was well tolerated with high rates of continued
      therapy at 60 to 90 days follow-up. Similar findings were observed for other
      evidence-based beta blockers. CONCLUSIONS: Carvedilol use at the time of HF
      hospital discharge is well tolerated, improves treatment rates, and is associated
      with an early survival benefit. These findings provide further support for
      guideline recommendations that carvedilol or other evidence-based beta blocker
      should be initiated before hospital discharge in stable patients with HF and
      LVSD.

PMID- 17174642
TI  - An obesity paradox in acute heart failure: analysis of body mass index and
      inhospital mortality for 108,927 patients in the Acute Decompensated Heart
      Failure National Registry.
AB  - BACKGROUND: Prior studies on chronic systolic heart failure (HF) have
      demonstrated that body mass index (BMI) is inversely associated with mortality,
      the so-called obesity paradox. The aim of this study was to determine whether BMI
      influences the mortality risk in acute decompensated HF, a subject not previously
      studied. METHODS: The Acute Decompensated Heart Failure National Registry was
      analyzed for acute HF hospitalizations in 263 hospitals in the United States from
      October 2001 through December 2004. Patients with documented height and weight
      were divided into BMI (measured in kilograms per square meter) quartiles.
      Inhospital mortality by BMI quartile for all the patients and for those with
      reduced (n = 43,255) and preserved (n = 37,901) systolic function was assessed.
      RESULTS: Body mass index quartiles in the 108,927 hospitalizations were QI (16.0
      23.6 kg/m2), QII (23.7-27.7 kg/m2), QIII (27.8-33.3 kg/m2), and QIV (33.4-60.0
      kg/m2). Patients in the higher BMI quartiles were younger, had more diabetes, and
      had a higher left ventricular ejection fraction. Inhospital mortality rates
      decreased in a near-linear fashion across successively higher BMI quartiles.
      After adjustments for age, sex, blood urea nitrogen, blood pressure, creatinine,
      sodium, heart rate, and dyspnea at rest, BMI quartile still predicted mortality
      risk. For every 5-U increase in BMI, the odds of risk-adjusted mortality was 10%
      lower (95% CI 0.88-0.93, P < .0001). CONCLUSIONS: In this cohort of hospitalized
      patients with HF, higher BMI was associated with lower inhospital mortality risk.
      The relationship between BMI and adverse outcomes in HF appears to be complex and
      deserving of further study.

PMID- 17174644
TI  - Association of atrial fibrillation and amino-terminal pro-brain natriuretic
      peptide concentrations in dyspneic subjects with and without acute heart failure:
      results from the ProBNP Investigation of Dyspnea in the Emergency Department
      (PRIDE) study.
AB  - BACKGROUND: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) testing is
      useful for diagnosis or exclusion of heart failure (HF) in dyspneic patients.
      Atrial fibrillation (AF) may cause dyspnea in the absence of acute HF and may
      also affect plasma levels of NT-proBNP. METHODS: We prospectively enrolled 599
      patients presenting with dyspnea to the emergency department and obtained a blood
      sample for NT-proBNP measurement. The diagnosis of AF was identified via
      presentation electrocardiogram. A final diagnosis of HF was determined by blinded
      study physicians using all available hospital records for each subject through 60
      days of follow-up. We assessed the association between the presence of AF and
      level of NT-proBNP in subsets of patients with and without HF. RESULTS: Of 599
      dyspneic patients, 75 (13%) were in AF at presentation; these patients had
      significantly higher median NT-proBNP levels when compared with those without AF
      (2934 vs 294 pg/mL, P < .0001). Among patients with acute HF, AF was present in
      28%; NT-proBNP levels were lower in those with AF versus those without (3488 vs
      4492 pg/mL, P < .001), but AF was not independently associated with NT-proBNP
      after multivariable adjustment. In patients without acute HF, median NT-proBNP
      concentrations were significantly higher in those with AF than in those without
      (932 vs 121 pg/mL, P = .02); in these subjects, AF was the strongest predictor of
      an NT-proBNP concentration in a range consistent with acute HF (odds ratio 9.94,
      95% CI 2.97-33.3, P < .001). CONCLUSION: Atrial fibrillation is associated with
      higher NT-proBNP concentrations in dyspneic patients, particularly in those
      without acute HF.

PMID- 17174645
TI  - Use and impact of inotropes and vasodilator therapy in hospitalized patients with
      severe heart failure.
AB  - BACKGROUND: Treatment of decompensated heart failure often includes the use of
      intravenous vasoactive medications, but the effect on outcome has not been
      clearly defined. METHODS: Data from 433 patients enrolled in the ESCAPE trial
      were analyzed to determine 6-month risks of all-cause mortality and all-cause
      mortality plus rehospitalization associated with the use of vasodilators,
      inotropes, and their combination. Patients had a mean left ventricular ejection
      fraction of 19%, 6-minute walk distance of 414 ft, and systolic blood pressure of
      106 mm Hg. The main outcome measure was multivariable risk-adjusted 6-month
      hazard ratios (HRs). RESULTS: Overall 6-month mortality was 19%. Risk-adjusted
      HRs were not statistically significant for vasodilators (1.39, 95% CI 0.64-3.00),
      but were significant for inotropes (2.14, 95% CI 1.10-4.15) and the combination
      (4.81, 95% CI 2.34-9.90). Risk-adjusted 6-month mortality plus rehospitalization
      HRs were not significant for vasodilators (1.20, 95% CI 0.81-1.78, P = .37), but
      were significant for inotropes (1.96, 95% CI 1.37-2.82, P < .001) and their
      combination (2.90, 95% CI 1.88-4.48, P = .001). The decision to use vasodilators
      or inotropes was determined by hemodynamic parameters and renal function, but the
      main factor was treatment site. CONCLUSIONS: In ESCAPE, the choice of medications
      was mainly determined by the treatment site. Use of inotropic agents was
      associated with adverse outcomes, whereas the use of vasodilators was not.
      Inotropes in combination with vasodilators identified a group with the highest
      mortality. Prospective studies are needed to establish the appropriate use of
      vasoactive medications in this population.

PMID- 17174647
TI  - Scar burden by myocardial perfusion imaging predicts echocardiographic response
      to cardiac resynchronization therapy in ischemic cardiomyopathy.
AB  - BACKGROUND: About 30% of patients with heart failure do not respond to cardiac
      resynchronization therapy (CRT). We hypothesized that scar burden can predict
      poor response to CRT in patients with ischemic cardiomyopathy (ICM). METHODS:
      Fifty patients (age, 68.5 +/- 9.2 years; 84% men; mean left ventricular ejection
      fraction (LVEF), 19.7% +/- 5.2%) with ICM who underwent CRT-defibrillator
      implantation and 201Tl single photon emission computed tomography myocardial
      perfusion imaging were included. Myocardial perfusion imaging studies were read
      quantitatively, generating a summed perfusion score (SPS). Left ventricular (LV)
      lead position was determined by chest radiography. Echocardiograms were performed
      before and after (median, 11.0 months) CRT. RESULTS: Echocardiographic response,
      defined as > or = 15% relative increase in LVEF, was documented in 28 (56%)
      patients. The mean SPS (18.8 +/- 11.3 vs 33.7 +/- 11.1; P = .000025) and the
      average scar density in the segments immediately adjacent to the LV lead (0.70 +/
      0.91 vs 1.64 +/- 0.82; P = .0004) were significantly lower in responders versus
      nonresponders. Global scar burden (r = -0.53; P = .00007), scar burden near the
      LV lead (r = -0.49; P = .0003), and the number of segments with a score of 4 (r =
      -0.53; P = .0007) inversely correlated with increase in LVEF after CRT. The
      hazard ratio for nonresponse increased with increasing tertiles of global SPS,
      scar density in the vicinity of the LV lead, and number of segments with
      transmural scar (ie, perfusion score = 4). CONCLUSIONS: Higher overall scar
      burden, a larger number of severely scarred segments, and greater scar density
      near the LV lead tip portend an unfavorable response to CRT in ICM patients.
      Prospective confirmation of these findings is warranted.

PMID- 17174646
TI  - Effects of acute changes in pulmonary wedge pressure on periodic breathing at
      rest in heart failure patients.
AB  - BACKGROUND: Patients with heart failure (HF) display a number of breathing
      abnormalities including periodic breathing (PB) at rest. Although the
      mechanism(s) contributing to PB remain unclear, we examined whether changes in
      pulmonary wedge pressure (PWP) and pulmonary vascular resistance (PVR) alter PB
      in patients with established HF. METHODS: We studied 12 male patients with HF
      (age, 50 +/- 11 years; ejection fraction, 18.3 +/- 3.8 %; New York Heart
      Association class, 3.2 +/- 0.4), with PB at rest, who are undergoing right heart
      catheterization with infusion of nitroprusside. RESULTS: At baseline, patients
      with HF displayed minute ventilation (V(E)) oscillations with amplitude of 5.5 +/
      2.7 L/min (57 +/- 34% of the average V(E)) and cycle length of 61 +/- 18
      seconds. Cardiac index (CI), PVR, and mean PWP averaged 2.0 +/- 0.4 L min(-1) m(
      2), 281.9 +/- 214.9 dyne/s per cm(-5), and 28.3 +/- 5.4 mm Hg, respectively.
      During nitroprusside infusion, CI increased to 3.1 +/- 0.6 L min(-1) m(-2), PVR
      decreased to 163.9 +/- 85.2 dyne/s per cm(-5), and PWP fell to 10.0 +/- 4.2 mm
      Hg. Nitroprusside reduced the amplitude (2.6 +/- 2.4 L/min, 23 +/- 21% of average
      V(E); P < .01) and cycle length (41.4 +/- 28.8 seconds; P < .01) of V(E)
      oscillations while abolishing oscillations in 3 patients. Although average V(E)
      and PaCO2 remained unchanged, there was a significant increase in the ratio of
      tidal volume to inspiratory time (V(T)/T(I); P < .01), suggesting an increase in
      ventilatory drive. The change in the amplitude of V(E) oscillations was
      positively correlated with the change in PWP (r = 0.75; P < .01), negatively
      correlated with the change in PVR (r = 0.63; P < .05), and not correlated with
      the change in CI. CONCLUSIONS: These data suggest that PWP (left atrial pressure)
      may play a direct role in the PB observed in HF at rest.

PMID- 17174648
TI  - Therapy with angiotensin-converting enzyme inhibitors, angiotensin II receptor
      blockers, and statins: no effect on ablation outcome after ablation of atrial
      fibrillation.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system and inflammation are
      supposed to play a key role in the pathogenesis of atrial fibrillation (AF). This
      retrospective clinical study was intended to assess the influence of drugs with
      antiinflammatory and/or renin-angiotensin-aldosterone system-modulating
      properties, namely angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin
      II receptor blockers (ARBs), and statins, on AF-free survival after AF ablation.
      METHODS: The study included 234 patients (23-80 years; 71.8% men) with drug
      resistant paroxysmal (n = 165) or persistent AF (n = 69) who either underwent a
      Lasso-guided segmental pulmonary vein isolation (n = 83) or a CARTO-guided left
      atrial circumferential ablation (n = 151). Treatment with statins (n = 113), ACE
      Is, or ARBs (n = 124), or a combination of a statin and an ACE-I or ARB (n = 75)
      was started >3 months before ablation and was continued during follow-up.
      RESULTS: After a median follow-up of 12.7 months, 64% of patients with paroxysmal
      and 45% of patients with persistent AF were free of AF. Statin use (hazard ratio
      [HR], 1.06; P = .79), ACE-I or ARB use (HR, 1.12; P = .59), and their combined
      use (statin + ACE-I/ARB; HR, 1.17; P = .54) did not significantly influence
      ablation outcome as assessed by Cox regression analysis. In addition, after
      multivariate adjustment for potential confounders, the examined drugs did not
      significantly affect ablation outcome. Ablation induced an acute up-regulation of
      C-reactive protein levels (preablation vs 48 hours postablation, 5.9 +/- 8.1 vs
      33.7 +/- 30 mg/L; P < .001) and other inflammatory markers. The examined drugs
      did not significantly alter baseline levels or ablation-induced up-regulation of
      inflammatory markers. CONCLUSIONS: The routine use of statins, ACE-Is, or ARBs
      did not result in an improved outcome of AF ablation.

PMID- 17174649
TI  - Persistent atrial fibrillation is associated with appropriate shocks and heart
      failure in patients with left ventricular dysfunction treated with an implantable
      cardioverter defibrillator.
AB  - AIM: The objective of this study was to investigate whether persistent atrial
      fibrillation (AF) and new-onset AF are associated with appropriate shocks,
      cardiovascular mortality, chronic heart failure (CHF), and inappropriate shocks
      in implantable cardioverter defibrillator (ICD) patients with left ventricular
      dysfunction. METHODS: We included 290 consecutive ICD patients with a documented
      left ventricular ejection fraction < or = 0.35 and compared outcomes between
      patients without AF (n = 207), those with persistent AF (n = 64), and those with
      new-onset AF (n = 19). RESULTS: The patients with persistent AF were older, more
      frequently had valve disease and cardiac surgery, and less frequently had
      coronary artery disease as compared with the patients without AF. Patients with
      persistent AF had a higher New York Heart Association class, however, left
      ventricular ejection fraction rates between these 2 groups were comparable (0.28
      +/- 0.07 vs 0.29 +/- 0.08, P = not significant). No difference was found between
      patients with new-onset AF and those without AF. During follow-up (2.6 +/- 1.9
      years), more patients with persistent AF received appropriate ICD shocks as
      compared with those without AF (24 [38%] vs 49 [24%], P = .04). Deterioration of
      CHF occurred more often in patients with persistent AF (19 [30%], P = .001) and
      those with new-onset AF (9 [47%], P < .001) as compared with patients without AF
      (31 [14%]). Multivariate analysis revealed that patients with persistent AF had
      an increased risk for appropriate ICD shocks (adjusted hazard ratio [HR] 1.9, 95%
      CI 1.2-3.2, P = .009). Persistent AF (adjusted HR 2.1, 95% CI 1.1-3.9, P = .03)
      and new-onset AF (adjusted HR 2.5, 95% CI 1.1-5.7, P = .02) were found to be
      independent risk indicators of CHF deterioration. CONCLUSIONS: In ICD patients
      with left ventricular dysfunction, persistent AF is associated with appropriate
      ICD shocks and deterioration of CHF. New-onset AF is related to deterioration of
      CHF.

PMID- 17174650
TI  - Incidence and clinical relevance of supraventricular tachyarrhythmias in
      pulmonary hypertension.
AB  - BACKGROUND: In patients with severe pulmonary hypertension (PH), right
      ventricular function is a main determinant of clinical stability and outcome.
      Supraventricular tachyarrhythmias (SVTs) may compromise cardiac function and
      threaten prognosis in patients with PH, but the incidence and clinical relevance
      of SVTs in PH and chronic right ventricular failure have not been evaluated.
      METHODS: In a 6-year retrospective single-center analysis, 231 consecutive
      patients followed for pulmonary arterial hypertension, or inoperable chronic
      thromboembolic PH were studied for SVTs. Analysis included incidence, clinical
      consequences, treatment, and outcome. RESULTS: Thirty-one episodes of SVT were
      observed in 27 of 231 patients (cumulative incidence 11.7%, annual risk 2.8% per
      patient), including atrial flutter (n = 15), atrial fibrillation (n = 13), and AV
      nodal reentry tachycardia (n = 3). Supraventricular tachyarrhythmia onset was
      almost invariably associated with marked clinical deterioration and right
      ventricular failure (84% of SVT episodes). Outcome was strongly associated with
      the type of SVT and restoration of sinus rhythm. During follow-up, cumulative
      mortality was low (6.3%, follow-up 26 +/- 23 months) when sinus rhythm was
      restored (all cases of AV nodal reentry tachycardia and atrial flutter). In
      contrast, 9 of 11 patients with sustained atrial fibrillation died from right
      ventricular failure (cumulative mortality 82%, follow-up 11 +/- 8 months).
      CONCLUSIONS: In patients with PH, SVTs constitute a relevant problem, often
      resulting in clinical deterioration. Sustained atrial fibrillation may be
      associated with a high risk of death from right ventricular failure.

PMID- 17174653
TI  - Aortic valve replacement for aortic stenosis is associated with improved aortic
      distensibility at long-term follow-up.
AB  - BACKGROUND: Aortic valve stenosis (AS) is the most frequent form of valvular
      heart disease. The number of studies evaluating the effect of aortic valve
      replacement (AVR) for AS on aortic vascular function is limited. The aim of the
      present study was to examine alterations in aortic distensibility in patients
      with AS during a 1-year follow-up after AVR. METHODS: Twelve patients with severe
      AS who underwent AVR were prospectively examined (mean age 65 +/- 11 years, 7
      men). Systolic and diastolic ascending aortic diameters (SD and DD, respectively)
      were recorded in M mode 3 cm above the aortic valve from a parasternal long-axis
      view. The SD and DD were measured at the time of maximum anterior motion of the
      aorta and at the start of the QRS complex, respectively. Aortic stiffness index
      (beta) was defined as [ln(SBP/DBP)] x DD/deltaD, where ln is the natural
      logarithm, SBP and DBP are the systolic and diastolic blood pressure values,
      respectively, and deltaD = SD - DD. RESULTS: As expected, aortic stenosis
      severity and left ventricular mass decreased significantly after AVR. Aortic
      diameter changes (systolic minus diastolic dimensions) progressively increased
      and the aortic stiffness index progressively improved to levels comparable with
      those of age-, sex-, and risk factor-matched controls at the 1-year assessment.
      CONCLUSIONS: Aortic valve replacement in patients with AS is associated with a
      progressive improvement in aortic distensibility to 1-year values similar to
      those of controls.

PMID- 17174652
TI  - Treatment practices and outcomes of patients with established peripheral arterial
      disease hospitalized with acute myocardial infarction in a community setting.
AB  - BACKGROUND: There are little contemporary data available describing the hospital
      and long-term outcomes of patients with peripheral arterial disease (PAD) who are
      hospitalized with acute myocardial infarction (AMI). The objectives of our
      population-based study were to examine the hospital and long-term outcomes, as
      well as the use of different treatment practices, among patients with established
      PAD who were hospitalized with AMI. METHODS: The study sample consisted of 4480
      patients hospitalized with AMI at all Worcester, Mass, medical centers in 4
      alternate years between 1997 and 2003. RESULTS: Among the metropolitan Worcester
      residents hospitalized with AMI, 13.5% had a history of PAD. Prior use of proven
      cardiac therapies in patients with, and without, PAD was less than optimal though
      more often used in patients with prior PAD. Patients with PAD were significantly
      less likely to be treated with thrombolytic therapy during hospitalization than
      patients without PAD. Patients with PAD were not at significantly increased risk
      of dying during hospitalization (adjusted OR 1.29, 0.95% CI 0.97-1.71), though
      they were at a significantly increased risk of dying at 1 year after hospital
      discharge (adjusted OR 2.00, 95% CI 1.58-2.52) in comparison with patients
      without prior PAD. CONCLUSIONS: Approximately 1 in 8 patients presenting with AMI
      in this community-wide study had a history of clinically recognized PAD. These
      patients are at increased risk of dying during the first year after hospital
      discharge. Our data indicate that there is a room for improvement for the
      enhanced use of effective treatment modalities and implementation of secondary
      prevention strategies in these high-risk patients.

PMID- 17174651
TI  - Ventricular ectopy: impact of self-reported stress after myocardial infarction.
AB  - BACKGROUND: Although psychologic stress has been implicated in the pathogenesis
      of ventricular arrhythmias, the relationship between self-reported stress and
      ventricular ectopy has not been evaluated under naturalistic conditions in acute
      post-myocardial infarction (MI) patients, a group at elevated risk for
      arrhythmias. MATERIALS AND METHODS: Diary-reported stress was measured during 24
      hour Holter monitoring in 80 patients (52 men and 28 women) approximately 12
      weeks after their MI. In addition, state and trait anxiety were measured using
      the Spielberger State and Trait Anxiety Inventory, which was administered at the
      beginning of the 24-hour Holter monitoring session. The relationships between
      diary-reported stress, anxiety, and ventricular ectopy were evaluated. RESULTS:
      Mean diary-reported stress was associated with total ventricular ectopy (beta =
      .29, P = .01). State anxiety was also associated with 24-hour ectopy (beta = .24,
      P = .04); however, trait anxiety was not significantly associated with ectopy.
      Temporal analyses of the relationship between stress and ectopy showed that diary
      reported stress was associated with an increase in the number of ventricular
      premature beats occurring in the following hour (beta = .74, P < .0001).
      CONCLUSIONS: These findings extend existing evidence linking psychologic factors
      to ventricular arrhythmias by demonstrating that psychologic stress predicts
      increased arrhythmic activity during routine daily activities in post-MI
      patients.

PMID- 17174654
TI  - Impression procedures and construction of a sectional denture for a patient with
      microstomia: a clinical report.
AB  - This article describes a modified impression procedure and a method of
      fabricating a 2-piece collapsible denture for a patient with limited oral opening
      as a result of the resection of a precancerous lesion on the maxillary lip.
      Fabricating the denture in 2 pieces (a smaller anterior piece and a larger,
      hinged, collapsible posterior piece) enabled the patient to place and remove the
      denture.

PMID- 17174655
TI  - Comparison of the shade matching ability of dental students using two light
      sources.
AB  - STATEMENT OF PROBLEM: Shade selection is affected by a host of variables,
      including lighting. PURPOSE: The purpose of this study was to assess the ability
      of dental students to match shades under natural lighting and using a light
      correcting device, specifically to determine whether there are differences based
      on: (1) year in school, (2) gender of student, and (3) light source. MATERIAL AND
      METHODS: A 14-item shade matching quiz (SMQ) and a questionnaire were field
      tested. No major modifications were made to SMQ or questionnaire. Demographic
      information included year in school, age, gender, previous experience, and
      Ishihara's Tests for Color-Blindness. The SMQ was administered on separate
      occasions during the spring and summer, under natural light (SMQ-NL) and using
      the light-correcting device (SMQ-CL). For each of the 14 items, students (n=216)
      were to select the matching shade tab from 5 preselected tabs. Statistical
      analyses included ANOVAs, paired t tests, and independent t tests (alpha=.05).
      RESULTS: A total of 165 male and 51 female students participated, with an average
      age of 26 years. SMQ scores of 10 color-deficient students were excluded. There
      were no significant differences in SMQ-NL and SMQ-CL among the first through
      fourth year students (ANOVA), nor between men and women (t tests). The SMQ scores
      were significantly higher with the light-correcting device than with natural
      light: 11.4 +/- 1.9 and 10.4 +/- 2.0, respectively (paired t test, P<.001). With
      and without the light-correcting device, the Vita C shades were less likely to be
      matched than the Vita A or B shades (paired t tests, P<.001). CONCLUSIONS: Dental
      students' shade matching abilities were better with a light-correcting source
      than under natural light. Gender and experience were not found to be factors in
      matching shades. The Vita C shades were least likely to be matched.

PMID- 17174656
TI  - Effect of esthetic core shades on the final color of IPS Empress all-ceramic
      crowns.
AB  - STATEMENT OF PROBLEM: Clinically relevant assessment of all-ceramic crowns
      supported by esthetic composite resin foundations has not been evaluated with
      regard to color reproducibility. PURPOSE: This in vitro study quantitatively
      evaluated the influence of different shades of composite resin foundations and
      resin cement on the final color of a leucite-reinforced all-ceramic material.
      MATERIAL AND METHODS: A total of 128 disks were fabricated; 64 (20 x 1 mm) were
      made of all-ceramic material (IPS Empress) and 64 (20 x 4 mm) of 4 different
      shades composite resin (Tetric Ceram). The ceramic and composite resin disks were
      luted using 2 shades (A3 and Transparent) of resin cement (Variolink II). Color
      was measured using a colorimeter configured with a diffuse illumination/0-degree
      viewing geometry, and Commission Internationale de l'Eclairage (CIE) L( *)a( *)b(
      *) values were directly calculated. Descriptive statistical analysis was
      performed, and color differences (DeltaE) for the average L( *), a( *) and b( *)
      color parameters were calculated. Repeated measures analysis of variance (ANOVA)
      was used to compare mean values and SDs between the different color combinations
      (alpha=.05). RESULTS: The CIE L( *)a( *)b( *) color coordinate values showed no
      significant differences for variation in color parameters due to the effect of
      the different composite resin shades (P=.24) or cement shades (P=.12). The mean
      color difference (DeltaE) value between the groups was 0.8. CONCLUSION: Within
      the limitations of this study, the use of different shades for composite resin
      cores and resin cements presented no statistically significant effect on the
      final color of IPS Empress all-ceramic material.

PMID- 17174657
TI  - Influence of illuminants on the color distribution of shade guides.
AB  - STATEMENT OF PROBLEM: Although a shade tab in a shade guide is matched to a
      natural tooth in the order of value, hue, and chroma, there are limited data on
      the color distribution of currently available shade guides sorted by these 3
      parameters. Furthermore, spectrophotometric color measurements of shade tabs
      differ depending on the standard illuminant employed. PURPOSE: The purpose of
      this study was to determine the color distributions of 2 shade guides in value
      (CIE L( *)), chroma (C( *)(ab)) and hue angle (h(o)) scale relative to the
      standard illuminants D(65), A, and F2. MATERIAL AND METHODS: Color of shade tabs
      (n=36) from 2 shade guides (Vita Lumin and Chromascop) were measured, and the
      distributions for CIE L( *), C( *)(ab) and h(o) values were compared. Color
      differences of shade tabs depending on the illuminant were calculated. The
      distributions of the ratios of CIE L( *) and C( *)(ab) values of each shade tab
      compared with the lowest value tab or the lowest chroma tab were determined. The
      data for the value, chroma, and hue angle within each shade guide were analyzed
      with a 2-way ANOVA with the factors of shade designation and type of illuminant
      (alpha=.05). Color difference caused by change of illuminant was analyzed with a
      2-way ANOVA with the factors of shade designation and pair of illuminants
      compared (alpha=.05). The Scheffe multiple comparison test was performed as a
      post hoc test. RESULTS: CIE L( *), C( *)(ab) and h(o) values were influenced by
      shade designation and type of illuminant in both shade guides. Color difference
      caused by change of the illuminant was influenced by the shade designation and
      pair of illuminants compared. The order of mean color differences of 16 Vita
      Lumin shade tabs by pairs of illuminants compared was as follows: DeltaE( *)(ab)
      (D(65)/F2) = 1.63 <DeltaE( *)(ab) (D(65)/A) = 2.22 <DeltaE( *)(ab) (A/F2) = 2.46
      (P<.05). The order of mean color differences of 20 Chromascop shade tabs was as
      follows: DeltaE( *)(ab) (D(65)/F2) = 2.45 <DeltaE( *)(ab) (D(65)/A) = 2.71
      <DeltaE( *)(ab) (A/F2) = 3.14 (P<.05). The distributions of value and chroma in
      both shade guides were arbitrary. CONCLUSION: Color distribution of 2 shade
      guides varied by the illuminant, and the range of color difference for shade tabs
      by the illuminant was 0.80 to 4.82, which may be clinically unacceptable (DeltaE(
      *)(ab) > 3.7). Color distribution of 2 shade guides by the value and chroma was
      not logical.

PMID- 17174659
TI  - Comparison of temperature increase in the pulp chamber during the polymerization
      of materials used for the direct fabrication of provisional restorations.
AB  - STATEMENT OF PROBLEM: Polymerization of resin materials used for the fabrication
      of provisional restorations is associated with an exothermic reaction. This
      temperature rise may present a serious biological problem, since it can cause
      iatrogenic thermal trauma to the pulp. PURPOSE: This in vitro study compared the
      temperature increase in the pulp chamber of a molar placed in contact with
      different resins used for the direct fabrication of provisional restorations.
      MATERIAL AND METHODS: Polymethyl methacrylate (Jet), polyethyl methacrylate
      (Snap), polyvinylethyl methacrylate (Trim), Bis-acrylic composite (Protemp II),
      and a VLP urethane dimethacrylate (Revotec LC) were compared with respect to
      their exothermic reaction properties during polymerization. A mandibular molar
      prepared for a complete coverage restoration was placed in an acrylic resin
      block. A thermal probe connected to a digital thermometer was placed into the
      pulp chamber. Specimens were submerged in a water bath to simulate intraoral
      conditions. The provisional resin materials tested were measured and mixed
      according to manufacturer's instructions. The resin mixture was placed into a
      vacuum-formed acetate template and was then positioned on the prepared molar
      tooth. The temperature was recorded during polymerization at 30-second intervals
      until it was evident that the peak temperature had been reached. Temperature
      increase was measured ( degrees C) for both the initial crown fabrication and the
      reline procedures. Data were analyzed with descriptive statistics, 1-way analysis
      of variance, and Tukey Honestly Significant Difference tests (alpha=.05).
      RESULTS: One-way ANOVA revealed significant differences (F=57.010, P<.0001) in
      temperature rise for different provisional resin materials. Mean temperature
      increase for the provisional crown fabrication ranged from 37.76 degrees C for
      the polyvinylethyl methacrylate to 39.40 degrees C for the polymethyl
      methacrylate. Mean temperature rise for the reline procedures ranged from 36.80
      degrees C for the polyvinylethyl methacrylate to 37.69 degrees C for the
      polymethyl methacrylate. All of the tested materials produced an exothermic
      chemical reaction. CONCLUSIONS: Polymethyl methacrylate produced the higher
      exothermic reaction in both initial crown fabrication and reline procedures.
      Polyethyl methacrylate, polyvinylethyl methacrylate, and Bis-acrylic resins
      tested were not significantly different from each other.

PMID- 17174658
TI  - Influence of ceramic surface conditioning and resin cements on microtensile bond
      strength to a glass ceramic.
AB  - STATEMENT OF PROBLEM: It is not clear how different glass ceramic surface
      pretreatments influence the bonding capacity of various luting agents to these
      surfaces. PURPOSE: The purpose of this study was to evaluate the microtensile
      bond strength (microTBS) of 3 resin cements to a lithia disilicate-based ceramic
      submitted to 2 surface conditioning treatments. MATERIAL AND METHODS: Eighteen 5
      x 6 x 8-mm ceramic (IPS Empress 2) blocks were fabricated according to
      manufacturer's instructions and duplicated in composite resin (Tetric Ceram).
      Ceramic blocks were polished and divided into 2 groups (n=9/treatment): no
      conditioning (no-conditioning/control), or 5% hydrofluoric acid etching for 20
      seconds and silanization for 1 minute (HF + SIL). Ceramic blocks were cemented to
      the composite resin blocks with 1 self-adhesive universal resin cement (RelyX
      Unicem) or 1 of 2 resin-based luting agents (Multilink or Panavia F), according
      to the manufacturer's instructions. The composite resin-ceramic blocks were
      stored in humidity at 37 degrees C for 7 days and serially sectioned to produce
      25 beam specimens per group with a 1.0-mm(2) cross-sectional area. Specimens were
      thermal cycled (5000 cycles, 5 degrees C-55 degrees C) and tested in tension at 1
      mm/min. Microtensile bond strength data (MPa) were analyzed by 2-way analysis of
      variance and Tukey multiple comparisons tests (alpha=.05). Fractured specimens
      were examined with a stereomicroscope (x40) and classified as adhesive, mixed, or
      cohesive. RESULTS: The surface conditioning factor was significant (HF+SIL > no
      conditioning) (P<.0001). Considering the unconditioned groups, the microTBS of
      RelyX Unicem was significantly higher (9.6 +/- 1.9) than that of Multilink (6.2
      +/- 1.2) and Panavia F (7.4 +/- 1.9). Previous etching and silanization yielded
      statistically higher microTBS values for RelyX Unicem (18.8 +/- 3.5) and
      Multilink (17.4 +/- 3.0) when compared to Panavia F (15.7 +/- 3.8). Spontaneous
      debonding after thermal cycling was detected when luting agents were applied to
      untreated ceramic surfaces. CONCLUSION: Etching and silanization treatments
      appear to be crucial for resin bonding to a lithia disilicate-based ceramic,
      regardless of the resin cement used.

PMID- 17174660
TI  - Effect of temperature on unpolymerized composite resin film thickness.
AB  - STATEMENT OF PROBLEM: Room temperature (RT) composite resins are viscous, and
      this condition may affect the ability of the material to flow and adapt to
      preparation walls. PURPOSE: The purpose of this study was to compare the film
      thickness of a variety of commercial composite resins heated prior to light
      polymerization. The film thickness of these heated materials was also compared to
      those of flowable products at RT. MATERIAL AND METHODS: Five flowable and 7
      conventional composite resins were used: 2 microfills, a nanofill hybrid, 2
      submicron hybrids, a trimodal hybrid, and a packable. Composite resin (0.05 mL)
      was pressed between 2 Mylar-covered glass plates (15 kg) for 180 seconds, light
      polymerized, and the thickness measured using a micrometer. When comparing
      conventional composite resin heated to 54 degrees C or 60 degrees C, the RT value
      was control, while the RT flowable values were control when compared to heated
      composite resin. (n=5/group). Data were analyzed using 1- and 2-way analysis of
      variance and the Tukey-Kramer post hoc test (alpha=.05). Correlation of filler
      content to flow potential was evaluated. Scanning electron microscopic analysis
      of polymerized specimens was characterized by filler size and shape. RESULTS:
      Room temperature conventional composite resin values varied in film thickness.
      Not all preheated products reduced in thickness. Thickness of the nanofill did
      not reduce, and one of the submicron hybrids reduced the greatest. No correlation
      existed between composite resin classification, filler content or shape, and film
      thickness. No difference in thickness existed between composite resins preheated
      to 54 degrees C and 60 degrees C. Room temperature and preheated conventional
      composite resin provided film thickness greater than that of flowable materials.
      CONCLUSIONS: Preheating conventional composite resin yields lower film thickness
      for some products, but flow cannot be attributed to composite resin
      classification, filler content, or shape. Preheated composite resin thickness was
      greater than that of all flowables.

PMID- 17174661
TI  - An overview of treatment considerations for esthetic restorations: a review of
      the literature.
AB  - Controversy persists regarding the treatment planning criteria for esthetic
      restorations. This article reviews the literature regarding the biocompatibility,
      marginal adaptation, color matching, patient selection, technique sensitivity,
      and mode and rate of failure of tooth-colored restorations. A Medline search was
      completed for the period from 1986 to 2006, along with a manual search, to
      identify pertinent English peer-reviewed articles and textbooks. The key words
      used were amalgam, posterior composite resin, ceramic inlays/onlays, CEREC,
      porcelain laminate veneers, all-ceramic crowns, and all-ceramic fixed partial
      dentures.

PMID- 17174662
TI  - Impact of water quality on setting of irreversible hydrocolloid impression
      materials.
AB  - STATEMENT OF PROBLEM: Setting of irreversible hydrocolloid impression materials
      is based on the ionic reaction between carboxylic groups and calcium ions and
      may, therefore, be affected by ionic species present in the mixing water. The
      impact of this phenomenon on the clinical performance of these materials has not
      been well documented. PURPOSE: The purpose of this study was to compare the
      setting behavior of irreversible hydrocolloid impression materials when mixed
      with tap and distilled water, and to determine the impact of typical cations
      present in tap water and their concentrations on the setting process. MATERIAL
      AND METHODS: Six brands of irreversible hydrocolloid impression materials
      (Kromopan 100, Xantalgin Select FS, Alginoplast, Elastic Plus, Ypeen, and Ypeen
      Premium) were mixed with tap and distilled water (control) according to
      manufacturers' recommendations. Elastic Plus was also mixed with aqueous
      solutions containing various concentrations of NaCl, CaCl(2), and AlCl(3) to
      determine the role of typical cations on setting. Using a controlled shear stress
      oscillatory rheometer, time changes of storage (G') and loss (G'') moduli during
      setting were measured at 23 degrees C and used to determine the working and
      setting times and rigidity of set impression materials. The sample size (n=3) for
      each material/mixing system was increased to 8 to increase reliability of
      measurements in systems where the effect of mixing water was low or variance of
      results was high. The data were analyzed (alpha=.05) using a t test (tap water),
      a 1-way ANOVA, a Tukey post hoc test (shear stress), and a nested ANOVA and
      Fisher Least Significant Difference post hoc analysis (cation and cation
      concentration). RESULTS: Statistical analysis showed significant (P<.001)
      acceleration in the setting rate for Kromopan 100, the working time of which was
      shorter with tap water by 23.4 seconds and the setting time, by 32.8 seconds.
      Similar significant reductions (in seconds) in both working and setting times,
      respectively, were found with Xantalgin Select FS (12.0, P<.001 and 23.6,
      P<.002), Alginoplast (24.3, P<.001 and 44.7, P<.005), and Elastic Plus (23.0,
      P<.001 and 22.0, P<.002), when compared with the same materials mixed with
      distilled water. At the same time, the rigidity of the set impression materials
      mixed with tap water increased by approximately 10%. With Ypeen Premium, the
      setting time decreased significantly by 20.0 seconds (P<.001) with tap water,
      while the working time and rigidity did not change. The setting behavior of Ypeen
      was not significantly affected by water quality. Acceleration of the setting
      reactions and increase in impression rigidity depended (P<.001) primarily on
      concentration and valency of cations present in mixing water. CONCLUSION: Setting
      of irreversible hydrocolloid impression materials can be significantly
      accelerated when tap water with high water hardness is used for mixing or when
      the mixing water contains higher concentrations of cations such as Na(+), Ca(2+),
      and Al(3+).

PMID- 17174663
TI  - The evaluation of the use of a delayed surgical obturator in dentate maxillectomy
      patients by considering days elapsed prior to commencement of postoperative oral
      feeding.
AB  - STATEMENT OF PROBLEM: As a prosthodontic treatment for a maxillectomy patient in
      the initial postoperative period, immediate surgical obturators during surgery
      have been advocated to restore and maintain the patient's oral function to a
      reasonable level. However, these may fit poorly because they are fabricated using
      preoperative casts. PURPOSE: The purpose of this study was to determine the
      comparative usefulness of a delayed surgical obturator. MATERIAL AND METHODS:
      During the period from 2000 to 2004, 29 patients underwent prosthodontic
      treatment after maxillectomy. Twenty-three patients who were dentate
      postoperatively and were treated with polyvinyl acetal (Merocel) packing and a
      delayed surgical obturator were included in this study. Patients who were
      edentulous postoperatively, who were treated with an immediate surgical obturator
      or whose data were incomplete were excluded. The records of 23 patients were
      reviewed to determine the usefulness of using a delayed surgical obturator by
      counting days required to start postoperative oral feeding. The median of days
      elapsed prior to commencement of postoperative oral feeding was compared with
      data from a study by Lapointe et al (1996). In the Lapointe et al study, the
      median days elapsed prior to beginning a clear fluid diet was 2 in the group
      using immediate surgical obturators. The data were analyzed using the 1-sample
      Wilcoxon signed rank test (alpha=.05). RESULTS: Days elapsed prior to
      commencement of postoperative oral feeding were less than those reported
      previously. Patients with Merocel packing began oral feeding, on average, 1.48
      days after the maxillectomy. The median number of days elapsed prior to
      commencement of postoperative oral feeding was 1. This time was earlier than the
      2 days for the Lapointe et al study (P=.0074). No major postoperative care
      complications occurred among the maxillectomy patients treated with a delayed
      surgical obturator. CONCLUSION: Delayed surgical obturators were successful in
      terms of the postoperative care of dentate maxillectomy patients and did not
      increase patient discomfort during early rehabilitative management.

PMID- 17174664
TI  - Accurate location of postpalatal seal area on the maxillary complete denture
      cast.

PMID- 17174665
TI  - A technique to fabricate metal occlusal surfaces for the overlay removable
      partial denture.

PMID- 17174666
TI  - Adhesive dentistry and endodontics. Part 2: bonding in the root canal system-the
      promise and the problems: a review.
AB  - One of the recent trends in endodontics has been the development of bonded
      obturating materials, in an effort to provide a more effective seal coronally and
      apically. Materials utilizing dentin adhesive technology have been borrowed from
      restorative dentistry and adapted to obturating materials. This review discusses
      the obstacles to effective bonding in the root canal system, the progress that
      has been made, and possible strategies for improved materials in the future. Much
      of the literature reviewed and many of the principles discussed are taken from
      the restorative dentistry literature and applied to the unique environment of the
      root canal system.

PMID- 17174667
TI  - Prevalence of selected bacterial named species and uncultivated phylotypes in
      endodontic abscesses from two geographic locations.
AB  - Evidence is mounting that the prevalence of some putative endodontic pathogens
      can significantly vary according to the geographic location in which samples were
      taken. This study aimed to provide additional knowledge on this subject by
      comparing the frequencies of 10 selected candidate endodontic pathogens in
      samples of acute apical abscesses obtained from two distinct geographic
      locations; Portland, OR, and Rio de Janeiro, Brazil. DNA was extracted from
      aspirates and used as template in nested PCR assays using 16S rRNA gene taxon
      specific oligonucleotide primers. Of the target species/phylotypes, Treponema
      denticola (73% of the cases), Porphyromonas endodontalis (70%), and Tannerella
      forsythia (57%) were the most prevalent taxa found in Brazilian samples.
      Dialister invisus (70% of the cases), P. endodontalis (63%) and Dialister
      pneumosintes (55%) were the most frequent taxa in the Portland, OR samples. Data
      analysis revealed that T. denticola and T. forsythia were significantly more
      detected in Brazilian samples than in the Portland, OR samples. Although D.
      invisus, Filifactor alocis, and Synergistes oral clone W090 were detected in many
      more samples from the Portland, OR patients, differences were not found to be
      statistically significant. These findings confirmed that some bacterial taxa can
      markedly differ in the frequencies they occur in samples from different
      locations. It remains to be clarified whether this observation translates into
      relevant therapeutic implications.

PMID- 17174668
TI  - Separation incidence of protaper rotary instruments: a large cohort clinical
      evaluation.
AB  - Separation is a potential risk when using any instrument in the root canal
      system. Presently, there are no large clinical studies investigating the
      separation incidence of the ProTaper rotary file system or the number of times a
      ProTaper rotary file can be safely used. The purpose of this study was to
      determine if the number of uses affects the separation incidence of ProTaper
      rotary instruments. 4652 consecutively treated root canals were performed in an
      endodontic group practice over a 17-month period. Both the separation incidence
      and the number of uses were tracked for each file. The overall rate of instrument
      fracture in this study was 2.4% with no significant differences over the first
      four uses. The results of this study indicate that ProTaper rotary files may be
      safely reused at least four times. The size of the rotary file, among other
      factors, will determine how many times a particular file should be used.

PMID- 17174669
TI  - Effect of calcium hydroxide-treated Prevotella nigrescens on the gene expression
      of matrix metalloproteinase and its inhibitor in MG63 cells.
AB  - The purpose of this study was to monitor the expression of matrix
      metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      produced by an osteoblastic cell line MG63 stimulated with Prevotella nigrescens
      lipopolysaccharides (LPS), and to compare the level of secretion before and after
      the P. nigrescens LPS was treated with calcium hydroxide [Ca(OH)2]. The
      underlying hypothesis is that the balance between MMP and TIMP secretion is the
      key to an understanding of the host degradative pathways involved in the
      pathogenesis of bacterial derived pulpal and periapical diseases. Confluent
      monolayers of MG63 human osteosarcoma cells were exposed to varying
      concentrations of P. nigrescens or Escherichia coli LPS. Alternately, confluent
      cultures were exposed to 10 microg/ml of bacterial LPS pretreated with Ca(OH)2
      (12.5 mg/ml) for 72 hours. At the end of the experimental period, total RNA was
      extracted and real-time quantitative polymerase chain reaction (PCR) was
      performed for MMP-1, TIMP-1, and glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH). The results showed that the expression of MMP-1 mRNA was low and
      invariant for the experimental period in the negative controls. However, exposure
      to P. nigrescens LPS increased expression after 48 hours. Expression of TIMP-1
      mRNA was highly increased at 24 and 48 hours with lower concentrations of LPS in
      contrast to a suppression with a concentration of 10 microg/ml. Treatment of P.
      nigrescens LPS with Ca(OH)2 resulted in a down-regulation of MMP-1, whereas
      pretreated E. coli LPS demonstrated no stimulatory activity for MMP-1 gene
      expression. Both types of LPS when pretreated with Ca(OH)2 induced slightly up
      regulated expression of TIMP-1.

PMID- 17174670
TI  - An analysis of current analgesic preferences for endodontic pain management.
AB  - A descriptive, cross sectional survey was developed to determine the preferences
      of endodontists when prescribing analgesics. Eleven clinical scenarios describing
      common endodontic diagnoses or procedures with specified severity of pain were
      provided. A survey was sent to 310 AAE members and 63 responded, providing a 20%
      response rate. Respondents were given various choices for analgesic prescription
      including various dosages of ibuprofen or acetaminophen (APAP), or combination
      narcotic medications. Data were analyzed by chi2 tests. Non-narcotics were
      preferred over narcotics for all clinical situations. Significantly more
      respondents selected ibuprofen 600 mg (4x a day) regardless of the severity of
      preoperative or postoperative pain (p<0.001). Educators and board-certified AAE
      members were less likely than nonboard certified AAE members to manage their
      patient's perceived severe pain with narcotic analgesics.

PMID- 17174671
TI  - C-shaped canal system in mandibular second molars Part III: The morphology of the
      pulp chamber floor.
AB  - The purpose of this study was to investigate the morphology of pulp chamber
      floors in mandibular second molars with a C-shaped canal system. Forty-four
      extracted mandibular second molars with C-shaped roots were collected from a
      native Chinese population. After the teeth were scanned by the micro-computed
      tomography (microCT), the pulp chamber floors were reconstructed three
      dimensionally using three-dimensional software. The reconstructed images were
      classified into four types based on the shape of the pulp chamber floor and the
      location of the dentin fusion between the peninsular-like floor and the pulp
      chamber wall. Of the 44 reconstructed pulpal floors, 38 (86.37%) were C-shaped
      (peninsula-like floor) in which 8 (18.18%) had a continuous C-shaped orifice
      (type I); 16 (36.37%) had a dentin fusion between the peninsula-like floor and
      buccal pulp chamber wall, forming one or two mesial orifice(s) and a distal
      orifice (type II); and 14 (31.82%) had a dentin fusion between the peninsula-like
      floor and the mesial pulp chamber wall, forming a large mesiobuccal-distal (MB-D)
      orifice and a small mesiolingual orifice (type III). Six (13.63%) teeth did not
      have a C-shaped floor configuration (type IV). The number and configuration of
      the canals at different levels below the orifices were analyzed. The results
      suggested that most teeth in this study with C-shaped roots also have a C-shaped
      pulpal floor and that a new classification of pulpal floor anatomy would be
      helpful in locating the C-shaped canals.

PMID- 17174672
TI  - A demographic analysis of vertical root fractures.
AB  - Teeth with vertical root fractures (VRFs) have complete or incomplete fractures
      that extends through the enamel, dentin and pulp, down the long axis of the
      tooth. Several different variables were investigated and statistically evaluated
      as to their correlation with the presence of VRFs. Specifically analyzed were
      gender, tooth location, age, radiographic and clinical findings, bruxism, and
      pulpal status. The data were collected from three different endodontists, from
      three different geographic locations, comprising a total of 227 teeth. Although
      VRFs may occur in conjunction with any of the parameters investigated, only
      certain factors were found to occur in a significant number of cases. The results
      indicate that VRFs are statistically more prevalent in mandibular molars and
      maxillary premolars. They are associated with periradicular bone loss, pain to
      percussion, extensive restorations, and seem to occur more often in females and
      older patients. However, VRFs are not necessarily related to periapical bone
      loss, a widening of the periodontal ligament space, associated periodontal
      pockets, a sinus tract, particular pulpal status, or bruxism.

PMID- 17174673
TI  - Immunoelectron microscopic analysis of CD11c-positive dendritic cells in the
      periapical region of the periodontal ligament of rat molars.
AB  - To increase understanding of structural and phenotypic characteristics of
      dendritic cells (DCs) in the periapical region of the periodontal ligament (PDL)
      of rat molars, we performed immunoelectron microscopy for CD11c, a previously
      untested DC marker. Results demonstrated that CD11c clearly recognized DCs,
      although it also labeled certain macrophage subpopulation(s). In the normal PDL,
      resident DCs that extended several long cytoplasmic processes from their oval to
      slender cell body were identified. When the PDL was bacterially challenged by
      three days of unsealed pulp exposure, relatively small, irregularly shaped DCs
      with many thin and short cytoplasmic processes, most likely representing newly
      recruited DCs, were detected. The ratio of DCs in CD11c+ cells was significantly
      higher than that in ED1 (anti-macrophages and DCs)-positive and OX6 (anti-major
      histocompatibility complex class II molecules)-positive cells in normal and
      challenged PDL.

PMID- 17174674
TI  - Evaluation of microleakage of roots filled with different techniques with a
      computerized fluid filtration technique.
AB  - The aim of this study was to compare the apical leakage of roots filled with
      different materials using a computerized fluid filtration technique. There were
      36 freshly extracted human maxillary central incisors selected. After preparation
      and irrigation, 3 experimental groups of 10 roots were constituted. Ten roots
      were filled with AH Plus and gutta-percha, 10 roots were filled with Sealapex and
      gutta-percha, and 10 roots were filled with Epiphany sealer and Resilon cone
      using a single cone technique. Three roots were used as a positive control and
      three roots were used as a negative control group. Evaluation of the apical
      leakages was performed with a computerized fluid filtration technique. According
      to the results, the difference between group 3 and 1 and group 3 and 2 was
      statistically significant (p<0.05). Although group 2 leaked the most, there was
      no significant difference between group 1 and 2.

PMID- 17174675
TI  - Variability of the diameter and taper of size #30, 0.04 nickel-titanium rotary
      files.
AB  - This investigation examined the variability of tip diameter (D0) and taper
      measurements among four different brands of #30, 0.04 nickel-titanium (NiTi)
      rotary files (n=15/brand). With all brands, the mean percent D0 difference from
      the manufacturer's reported (nominal) diameter (Profile GT, 1.73+/-2.03%; Endo
      Sequence, 3.38+/-3.91%; K3, 4.56+/-2.36%; Profile, 6.13+/-4.07%) indicated that
      files tended to be larger than the nominal diameter. A 1-factor ANOVA and Tukey's
      post hoc test revealed a statistically significant difference (p<or=0.05) between
      Profile GT (smallest difference from nominal) and Profile (largest difference).
      The ANOVA also indicated no significant effect (p>0.05) of brand on the mean
      percent difference of the measured taper compared to the nominal taper with the
      majority of measurements at either 0.039 or 0.040 taper.

PMID- 17174676
TI  - Immediate and 24-hour evaluation of the interfacial strengths of fiber posts.
AB  - This study examined the contribution of testing time on the interfacial strengths
      of fiber posts to radicular dentin. Twenty-five fiber posts were luted to root
      segments with resin cements and a zinc phosphate cement. Immediately upon setting
      of the materials, the roots were sectioned into slices and randomly divided into
      two subgroups, depending on testing time (immediate vs. 24-hours), for push-out
      test. The results showed an improvement on the interfacial strength after 24
      hours of storage. When data were pooled for each cement, the interfacial
      strengths (MPa) were: Optibond Solo Plus/Nexus: 10.3+/-3.8a; zinc phosphate
      cement: 10.1+/-2.7a; Multilink: 9.6+/-3.8ab; RelyX Unicem: 7.1+/-4.9bc; AllBond
      2/Duolink: 6.7+/-3.5c (groups with same superscript letter were not statistically
      significant). It is concluded that bond strength can increase during the first 24
      hours and that the interfacial strength is predominantly contributed by
      frictional retention.

PMID- 17174677
TI  - Electric pulp tester conductance through various interface media.
AB  - A conducting media is necessary when using an electric pulp tester (EPT). The
      objective of this study was to observe differences in conductance through various
      media. We hypothesized that variations in current conductance through different
      media exist. The pulp chamber of a freshly extracted premolar was exposed, and
      the cathode of a voltmeter was inserted into the pulpal tissue. The anode was
      coupled to the EPT handpiece. The measurement taken during dry (no interface
      media) EPT tip-to-tooth contact was 0 V, which served as negative control. EPT
      tip directly touching the cathode measured 3.9V and served as positive control. A
      number of media readily available in the dental office were tested. Data was
      analyzed using single factor ANOVA. Listerine (3.3) conducted the most voltage
      (p<0.5). Of nonliquids, K-Y Brand UltraGel and Crest Baking Soda & Peroxide
      Whitening Tartar Control toothpaste recorded significantly (p<0.05) higher
      voltage readings (1.4 V).

PMID- 17174678
TI  - Efficacy of a new brush-covered irrigation needle in removing root canal debris:
      a scanning electron microscopic study.
AB  - The usefulness of NaviTip FX, a brush-covered irrigation needle, in endodontic
      therapy has never been reported. Therefore, the purpose of this investigation was
      to evaluate the cleaning efficacy of this new brush-covered irrigation needle,
      the NaviTip FX. Thirty single-rooted teeth were randomly divided into two equal
      groups and instrumented using the crown-down technique with 0.04 taper ProFile.
      Following each file use, the canals were irrigated with 1 ml of 5.25% NaOCl using
      the NaviTip FX needle for group 1 or using the same needle without the brush for
      group 2. At the end of instrumentation, the roots were cut longitudinally and
      each half was divided into three equal parts. The specimens were then routinely
      prepared for scanning electron microscopic evaluation. The results showed that
      using the NaviTip FX produced cleaner coronal thirds of instrumented root canals
      compared to the control group. On the other hand, the middle and apical thirds
      were not statistically significantly different between the two groups. Further
      development of this irrigation technique to improve cleanliness of the apical and
      middle thirds is required before the NaviTip FX can be recommended for routine
      use during root canal therapy.

PMID- 17174679
TI  - The antimicrobial effect of chloroform on Enterococcus faecalis after gutta
      percha removal.
AB  - The purpose of this in vitro study was to evaluate the antimicrobial
      effectiveness of chloroform on Enterococcus faecalis when used as a gutta-percha
      solvent during endodontic retreatment. Bilaterally matched human teeth were
      instrumented, infected with E. faecalis, and obturated. The gutta-percha was then
      removed using either chloroform or saline. Bacterial samples were collected after
      gutta-percha removal and following additional apical enlargement. A significant
      difference was seen (p<0.05) between the number of colony forming units (CFU) of
      E. faecalis for teeth retreated using chloroform (mean 21+56 CFU/ml) versus
      saline (mean 280+480 CFU/ml). Negative cultures were obtained in 11 of 17
      chloroform samples and none of the saline samples. Samples taken after apical
      enlargement two sizes larger than the original master apical file showed a
      significant difference (p<0.05) between teeth retreated using chloroform versus
      saline. Negative cultures were seen in 9 of 17 chloroform samples and 1 of 17
      saline samples. This study demonstrated that the use of chloroform during
      endodontic retreatment significantly reduced intracanal levels of cultivatable E.
      faecalis.

PMID- 17174680
TI  - Comparison of seal after obturation techniques using a polydimethylsiloxane-based
      root canal sealer.
AB  - A polydimethylsiloxane-based sealer (GuttaFlow) was used for filling single
      rooted teeth with four obturation techniques. Prefitted gutta-percha master-cones
      were employed in groups 1 to 3 with backfilling of the sealer. Apical third of
      the roots were first filled with GuttaFlow, and sealer-coated master cones were
      seated with up-and-down motion (group 1) or rotated to place (group 2). Master
      cones were used as carriers for introducing GuttaFlow into the canals (group 3).
      Canals were filled with GuttaFlow without master-cones (group 4). Canals were
      filled with AH Plus/gutta-percha using warm vertical compaction (control group
      5). All obturated canals were tested for leakage after 1, 6, and 12 weeks using
      the fluid filtration technique. All groups exhibited equivalent seal regardless
      of time except for more extensive leakage in group 3. The use of GuttaFlow with a
      single gutta-percha master cone creates an apical seal that is equivalent to that
      produced with gutta-percha/AH Plus sealer using warm vertical compaction.

PMID- 17174681
TI  - Vickers hardness investigation of work-hardening in used NiTi rotary instruments.
AB  - A contributing mechanism for clinical failure of NiTi rotary instruments might be
      excessive work hardening. Vickers hardness was measured with 300 gm load near the
      flutes in three regions (D2-D4, D6-D10, and D14 towards the shank) for nine
      representative clinically used ProFile GT instruments that had been axially
      sectioned (10 measurements in each region). Consistent values could not be
      obtained at D1. Minimum hardness occurred at D2 to D4, with means from 313 to 324
      (SD from 7 to 16). Maximum hardness with means ranging widely from 330 to 481 was
      found beyond D14. Mean hardness at D2 to D4 was 320 for an as-received ProFile
      instrument. Because a mean Vickers hardness of 326 has been reported for a shape
      memory NiTi orthodontic wire product, it can be concluded that the NiTi
      instruments did not experience substantial work hardening at D2 to D4 during
      clinical use, in agreement with previous differential scanning calorimetric
      analyses.

PMID- 17174682
TI  - The use of a setting accelerator and its effect on pH and calcium ion release of
      mineral trioxide aggregate and white Portland cement.
AB  - The aim of this study was to evaluate the influence of adding 10% calcium
      chloride (CaCl2) indicated as setting accelerator on pH and release of calcium
      ions of commercially available materials: ProRoot MTA (tooth-colored formula),
      MTA Branco, and White Portland cement. The products were mixed for 30 seconds in
      previously established ratios. To estimate the values of pH and release of
      calcium ion, polyethylene tubes were filled with the materials and immersed in
      containers with 10 ml of deionized water. The analyses were performed baseline,
      30 minutes, 60 minutes, and 24 hours after the mixing process. A pHmeter
      (MicroNal B 371, Sao Paulo, SP, Brazil) and an atomic absorption
      spectrophotometer (Model GBC 904; CG Corp, Melbourne, Australia) equipped with a
      hollow cathode lamp were used to determine the data. According to the Student's t
      test, the comparison between the pure and the CaCl2-added products indicated that
      the presence of this substance increased immediately the pH, although the results
      were very similar when they were analyzed in the other intervals. In addition,
      products with CaCl2 released more calcium ions than pure materials in the 24-hour
      period (p<0.05). The results revealed that the addition of CaCl2 to MTA enhanced
      the physicochemical properties of this product. Thus, materials mixed with CaCl2
      became easier to handle and needed lower amounts of water in the mixing process.

PMID- 17174683
TI  - A comparison of the canal centering ability of ProFile, K3, and RaCe Nickel
      Titanium rotary systems.
AB  - The purpose of this investigation was to compare the ability of three Nickel
      Titanium (NiTi) rotary systems (ProFile, K3, and RaCe) to centralize
      instrumentation relative to the original canal location and to determine the
      distance of transportation of these canals. Sixty mesial root canals mandibular
      molars with curvature ranging from 15 to 40 degrees were selected. The canals
      were divided randomly into three groups of 20 canals each. The roots were
      sectioned horizontally at 3 mm, 5 mm, and 8 mm from the root apex. Teeth were
      reassembled and instrumented according to the manufacturer's guidelines, with all
      groups being prepared to size 30 (0.06) taper master apical file. The cross
      sections were digitally scanned before and after preparation, and image analysis
      software was used to assess the centering ability and the extent and direction of
      transportation. The three groups were statistically compared with analysis of
      variance and Tukey's HSD test. The results indicated that all three rotary NiTi
      systems used in this study were able to preserve dentin structure. The RaCe
      system significantly showed most transportation (p<0.05). The ProFile system was
      found to be the best for all variables measured in this study.

PMID- 17174684
TI  - The rapid sterilization of gutta-percha cones with sodium hypochlorite and
      glutaraldehyde.
AB  - The purpose of this in vitro study was to evaluate the effectiveness of sodium
      hypochlorite and glutaraldehyde for rapid sterilization of gutta-percha cones
      contaminated with Bacillus subtilis ATCC 6633. Cones were treated with either 2%
      glutaraldehyde or 2.5% sodium hypochlorite. The gutta-percha cones were
      sterilized with a 2.5% sodium hypochlorite solution throughout the test.
      Glutaraldehyde did not decontaminate the gutta-percha cones even after 15 minutes
      of contact. All positive controls showed positive results during the first 24
      hours. Negative controls were followed up for 24 and 48 hours and demonstrated
      the efficiency of previous sterilization. No microbial growth was observed in the
      groups tested. Even though gutta-percha cones are usually sterile during storage,
      they can be easily contaminated if incorrectly manipulated. NaOCl at 2.5%
      concentration is an effective agent for decontamination of gutta-percha cones at
      no additional cost.

PMID- 17174685
TI  - Immature teeth with periradicular periodontitis or abscess undergoing
      apexogenesis: a paradigm shift.
AB  - Four clinical cases of immature teeth that developed periradicular periodontitis
      or abscess underwent a conservative treatment approach, i.e. without canal
      instrumentation. Instead, only copious 2.5% NaOCl irrigation was performed. All
      cases presented herein developed mature apices after 7 months to 5 years after
      the initial treatment without complications, although narrowing canal space was
      observed. Our clinical observations support a shifting paradigm toward a
      conservative approach by providing a favorable environment for tissue
      regeneration. The mechanism of this continued development and formation of the
      root end is discussed.

PMID- 17174686
TI  - Nonsurgical endodontic retreatment of geminated teeth: a case report.
AB  - The purpose of this case presentation is to describe nonsurgical retreatment of
      anterior teeth with gemination. A 21-year-old male patient was referred for
      endodontic treatment of his maxillary left lateral incisor. In the clinical
      examination, a large crown was observed in the left maxillary incisor region when
      compared with the right maxillary lateral incisor. In the present case, a tooth
      gemination of a maxillary lateral incisor has been described. A periapical
      radiograph showed that the tooth had partially separated two crowns having a
      single root and one root canal, but the access cavity of the distal crown had not
      been opened, and the root canal had been obturated with single cone technique.
      Nonsurgical endodontic retreatment was decided for geminated lateral incisor. At
      the 6-month follow-up, the tooth was asymptomatic and there was no radiolucency
      around the apical region.

PMID- 17174688
TI  - Reorganising research in the UK.

PMID- 17174687
TI  - Endodontic management of a fused maxillary lateral incisor with a supernumerary
      tooth: a case report.
AB  - Fusion is a rare occurrence and its definitive diagnosis is of prime importance
      for successful root canal treatment. This case report discusses the endodontic
      and esthetic management of fused maxillary lateral incisor with a supernumerary
      tooth that presented with spacing between the fused tooth and the adjacent
      central incisor. Nonsurgical endodontic treatment was performed on the fused
      teeth followed by postendodontic esthetic restoration. The patient remained
      symptom-free and there was a reduction in the size of periapical radiolucency
      after 1 year.

PMID- 17174689
TI  - Strategies for stroke management.

PMID- 17174690
TI  - Out of the frying pan...

PMID- 17174691
TI  - Initial strategy for antiretroviral-naive patients.

PMID- 17174693
TI  - DDT: a polluted debate in malaria control.

PMID- 17174692
TI  - Pralidoxime for organophosphate poisoning.

PMID- 17174694
TI  - Art for women's health.

PMID- 17174697
TI  - Strategies for reducing maternal mortality.

PMID- 17174698
TI  - Measuring maternal mortality.

PMID- 17174699
TI  - Reducing maternal mortality where rates are greatest.

PMID- 17174700
TI  - Strategies for reducing maternal mortality.

PMID- 17174701
TI  - Maternal survival: more research is needed.

PMID- 17174702
TI  - Oral misoprostol for postpartum haemorrhage.

PMID- 17174703
TI  - New guidance on doctors' behaviour from the UK Prime Minister.

PMID- 17174704
TI  - A comparison of three highly active antiretroviral treatment strategies
      consisting of non-nucleoside reverse transcriptase inhibitors, protease
      inhibitors, or both in the presence of nucleoside reverse transcriptase
      inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised
      trial.
AB  - BACKGROUND: Long-term data from randomised trials on the consequences of
      treatment with a protease inhibitor (PI), non-nucleoside reverse transcriptase
      inhibitor (NNRTI), or both are lacking. Here, we report results from the FIRST
      trial, which compared initial treatment strategies for clinical, immunological,
      and virological outcomes. METHODS: Between 1999 and 2002, 1397 antiretroviral
      treatment-naive patients, presenting at 18 clinical trial units with 80 research
      sites in the USA, were randomly assigned in a ratio of 1:1:1 to a protease
      inhibitor (PI) strategy (PI plus nucleoside reverse transcriptase inhibitor
      [NRTI]; n=470), a non-nucleoside reverse transcriptase inhibitor (NNRTI) strategy
      (NNRTI plus NRTI; n=463), or a three-class strategy (PI plus NNRTI plus NRTI;
      n=464). Primary endpoints were a composite of an AIDS-defining event, death, or
      CD4 cell count decline to less than 200 cells per mm3 for the PI versus NNRTI
      comparison, and average change in CD4 cell count at or after 32 months for the
      three-class versus combined two-class comparison. Analyses were by intention-to
      treat. This study is registered ClinicalTrials.gov, number NCT00000922. FINDINGS:
      1397 patients were assessed for the composite endpoint. A total of 388
      participants developed the composite endpoint, 302 developed AIDS or died, and
      188 died. NNRTI versus PI hazard ratios (HRs) for the composite endpoint, for
      AIDS or death, for death, and for virological failure were 1.02 (95% CI 0.79
      1.31), 1.07 (0.80-1.41), 0.95 (0.66-1.37), and 0.66 (0.56-0.78), respectively.
      1196 patients were assessed for the three-class versus combined two-class primary
      endpoint. Mean change in CD4 cell count at or after 32 months was +234 cells per
      mm3 and +227 cells per mm3 for the three-class and the combined two-class
      strategies (p=0.62), respectively. HRs (three-class vs combined two-class) for
      AIDS or death and virological failure were 1.15 (0.91-1.45) and 0.87 (0.75-1.00),
      respectively. HRs (three-class vs combined two-class) for AIDS or death were
      similar for participants with baseline CD4 cell counts of 200 cells per mm3 or
      less and of more than 200 cells per mm3 (p=0.38 for interaction), and for
      participants with baseline HIV RNA concentrations less than 100 000 copies per mL
      and 100,000 copies per mL or more (p=0.26 for interaction). Participants assigned
      the three-class strategy were significantly more likely to discontinue treatment
      because of toxic effects than were those assigned to the two-class strategies (HR
      1.58; p<0.0001). INTERPRETATION: Initial treatment with either an NNRTI-based
      regimen or a PI-based regimen, but not both together, is a good strategy for long
      term antiretroviral management in treatment-naive patients with HIV.

PMID- 17174706
TI  - Epidemiology of antituberculosis drug resistance (the Global Project on Anti
      tuberculosis Drug Resistance Surveillance): an updated analysis.
AB  - BACKGROUND: The burden of tuberculosis is compounded by drug-resistant forms of
      the disease. This study aimed to analyse data on antituberculosis drug resistance
      gathered by the WHO and International Union Against Tuberculosis and Lung Disease
      Global Project on Anti-tuberculosis Drug Resistance Surveillance. METHODS: Data
      on drug susceptibility testing for four antituberculosis drugs--isoniazid,
      rifampicin, ethambutol, and streptomycin--were gathered in the third round of the
      Global Project (1999-2002) from surveys or ongoing surveillance in 79 countries
      or geographical settings. These data were combined with those from the first two
      rounds of the project and analyses were done. Countries that participated
      followed a standardised set of guidelines to ensure comparability both between
      and within countries. FINDINGS: The median prevalence of resistance to any of the
      four antituberculosis drugs in new cases of tuberculosis identified in 76
      countries or geographical settings was 10.2% (range 0.0-57.1). The median
      prevalence of multidrug resistance in new cases was 1.0% (range 0.0-14.2).
      Kazakhstan, Tomsk Oblast (Russia), Karakalpakstan (Uzbekistan), Estonia, Israel,
      the Chinese provinces Liaoning and Henan, Lithuania, and Latvia reported
      prevalence of multidrug resistance above 6.5%. Trend analysis showed a
      significant increase in the prevalence of multidrug resistance in new cases in
      Tomsk Oblast (p<0.0001). Hong Kong (p=0.01) and the USA (p=0.0002) reported
      significant decreasing trends in multidrug resistance in new cases of
      tuberculosis. INTERPRETATION: Multidrug resistance represents a serious challenge
      for tuberculosis control in countries of the former Soviet Union and in some
      provinces of China. Gaps in coverage of the Global Project are substantial, and
      baseline information is urgently required from several countries with high
      tuberculosis burden to develop appropriate control interventions.

PMID- 17174705
TI  - Continuous pralidoxime infusion versus repeated bolus injection to treat
      organophosphorus pesticide poisoning: a randomised controlled trial.
AB  - BACKGROUND: The role of oximes for the treatment of organophosphorus pesticide
      poisoning has not been conclusively established. We aimed to assess the
      effectiveness of a constant pralidoxime infusion compared with repeated bolus
      doses to treat patients with moderately severe poisoning from organophosphorus
      pesticides. METHODS: 200 patients were recruited to our single-centre, open
      randomised controlled trial after moderately severe poisoning by
      anticholinesterase pesticide. All were given a 2 g loading dose of pralidoxime
      over 30 min. Patients were then randomly assigned to control and study groups.
      Controls were given a bolus dose of 1 g pralidoxime over 1 h every 4 h for 48 h.
      The study group had a constant infusion of 1 g over an hour every hour for 48 h.
      Thereafter, all patients were given 1 g every 4 h until they could be weaned from
      ventilators. Analysis was by intention to treat. Primary outcome measures were
      median atropine dose needed within 24 h, proportion of patients who needed
      intubation, and number of days on ventilation. The study is registered at
      http://www.clinicaltrials.gov with the identifier NCT00333944. FINDINGS: 100
      patients were assigned the high-dose regimen, and 100 the control regimen. There
      were no drop-outs. Patients receiving the high-dose pralidoxime regimen required
      less atropine during the first 24 h than controls (median 6 mg vs 30 mg;
      difference 24 mg [95% CI 24-26, p<0.0001]). 88 (88%) and 64 (64%) of controls and
      high-dose patients, respectively, needed intubation during admission to hospital
      (relative risk=0.72, 0.62-0.86, p=0.0001). Control patients required ventilatory
      support for longer (median 10 days vs 5 days; difference 5 days [5-6, p<0.0001]).
      INTERPRETATION: A high-dose regimen of pralidoxime, consisting of a constant
      infusion of 1 g/h for 48 h after a 2 g loading dose, reduces morbidity and
      mortality in moderately severe cases of acute organophosphorus-pesticide
      poisoning.

PMID- 17174707
TI  - Dietary folate deficiency and bilateral retinal haemorrhages.

PMID- 17174708
TI  - Generalised anxiety disorder.
AB  - Generalised anxiety disorder is a persistent and common disorder, in which the
      patient has unfocused worry and anxiety that is not connected to recent stressful
      events, although it can be aggravated by certain situations. This disorder is
      twice as common in women than it is in men. Generalised anxiety disorder is
      characterised by feelings of threat, restlessness, irritability, sleep
      disturbance, and tension, and symptoms such as palpitations, dry mouth, and
      sweating. These symptoms are recognised as part of the anxiety syndrome rather
      than independent complaints. The symptoms overlap greatly with those of other
      common mental disorders and we could regard the disorder as part of a spectrum of
      mood and related disorders rather than an independent disorder. Generalised
      anxiety disorder has a relapsing course, and intervention rarely results in
      complete resolution of symptoms, but in the short term and medium term, effective
      treatments include psychological therapies, such as cognitive behavioural
      therapy; self-help approaches based on cognitive behavioural therapy principles;
      and pharmacological treatments, mainly selective serotonin reuptake inhibitors.

PMID- 17174709
TI  - Developmental neurotoxicity of industrial chemicals.
AB  - Neurodevelopmental disorders such as autism, attention deficit disorder, mental
      retardation, and cerebral palsy are common, costly, and can cause lifelong
      disability. Their causes are mostly unknown. A few industrial chemicals (eg,
      lead, methylmercury, polychlorinated biphenyls [PCBs], arsenic, and toluene) are
      recognised causes of neurodevelopmental disorders and subclinical brain
      dysfunction. Exposure to these chemicals during early fetal development can cause
      brain injury at doses much lower than those affecting adult brain function.
      Recognition of these risks has led to evidence-based programmes of prevention,
      such as elimination of lead additives in petrol. Although these prevention
      campaigns are highly successful, most were initiated only after substantial
      delays. Another 200 chemicals are known to cause clinical neurotoxic effects in
      adults. Despite an absence of systematic testing, many additional chemicals have
      been shown to be neurotoxic in laboratory models. The toxic effects of such
      chemicals in the developing human brain are not known and they are not regulated
      to protect children. The two main impediments to prevention of neurodevelopmental
      deficits of chemical origin are the great gaps in testing chemicals for
      developmental neurotoxicity and the high level of proof required for regulation.
      New, precautionary approaches that recognise the unique vulnerability of the
      developing brain are needed for testing and control of chemicals.

PMID- 17174710
TI  - A new Director General for WHO--an opportunity for bold and inspirational
      leadership.

PMID- 17174711
TI  - A cool case: hypothermia and adrenal failure.

PMID- 17174713
TI  - Assessing dose of the representative person for the purpose of radiation
      protection of the public. ICRP publication 101. Approved by the Commission in
      September 2005.
AB  - The Commission intended that its revised recommendations should be based on a
      simple, but widely applicable, system of protection that would clarify its
      objectives and provide a basis for the more formal systems needed by operating
      managers and regulators. The recommendations would establish quantified
      constraints, or limits, on individual dose from specified sources. These dose
      constraints apply to actual or representative people who encounter occupational,
      medical, and public exposures. This report updates the previous guidance for
      estimating dose to the public. Dose to the public cannot be measured directly
      and, in some cases, it cannot be measured at all. Therefore, for the purpose of
      protection of the public, it is necessary to characterise an individual, either
      hypothetical or specific, whose dose can be used for determining compliance with
      the relevant dose constraint. This individual is defined as the 'representative
      person'. The Commission's goal of protection of the public is achieved if the
      relevant dose constraint for this individual for a single source is met and
      radiological protection is optimised. This report explains the process of
      estimating annual dose and recognises that a number of different methods are
      available for this purpose. These methods range from deterministic calculations
      to more complex probabilistic techniques. In addition, a mixture of these
      techniques may be applied. In selecting characteristics of the representative
      person, three important concepts should be borne in mind: reasonableness,
      sustainability, and homogeneity. Each concept is explained and examples are
      provided to illustrate their roles. Doses to the public are prospective (may
      occur in the future) or retrospective (occurred in the past). Prospective doses
      are for hypothetical individuals who may or may not exist in the future, while
      retrospective doses are generally calculated for specific individuals. The
      Commission recognises that the level of detail afforded by its provision of dose
      coefficients for six age categories is not necessary in making prospective
      assessments of dose, given the inherent uncertainties usually associated with
      estimating dose to the public and with identification of the representative
      person. It now recommends the use of three age categories for estimating annual
      dose to the representative person for prospective assessments. These categories
      are 0-5 years (infant), 6-15 years (child), and 16-70 years (adult). For
      practical implementation of this recommendation, dose coefficients and habit data
      for a 1-year-old infant, a 10-year-old child, and an adult should be used to
      represent the three age categories. In a probabilistic assessment of dose,
      whether from a planned facility or an existing situation, the Commission
      recommends that the representative person should be defined such that the
      probability is less than about 5% that a person drawn at random from the
      population will receive a greater dose. If such an assessment indicates that a
      few tens of people or more could receive doses above the relevant constraint, the
      characteristics of these people need to be explored. If, following further
      analysis, it is shown that doses to a few tens of people are indeed likely to
      exceed the relevant dose constraint, actions to modify the exposure should be
      considered. The Commission recognises the role that stakeholders can play in
      identifying characteristics of the representative person. Involvement of
      stakeholders can significantly improve the quality, understanding, and
      acceptability of the characteristics of the representative person and the
      resulting estimated dose.

PMID- 17174715
TI  - The optimisation of radiological protection: broadening the process. ICRP
      publication 101. Approved by the Commission in September 2005.
AB  - The principle of optimisation of radiation protection is defined by the
      Commission as the source-related process to keep the magnitude of individual
      doses, the number of people exposed, and the likelihood of potential exposure as
      low as reasonably achievable below the appropriate dose constraints, with
      economic and social factors being taken into account. According to the revised
      recommendations of ICRP, this process of optimisation below constraint should be
      applied whatever the exposure situation; i.e. planned, emergency, and existing.
      The previous recommendations for the practical implementation of the optimisation
      process are still valid. It must be implemented through an ongoing, cyclical
      process that involves the evaluation of the exposure situation to identify the
      need for action, the identification of the possible protective options to keep
      the exposure as low as reasonably achievable, the selection of the best option
      under the prevailing circumstances, the implementation of the selected option
      through an effective optimisation programme, and regular review of the exposure
      situation to evaluate if the prevailing circumstances call for the implementation
      of corrective protective actions. However, the way in which the optimisation
      process should be implemented is now viewed more broadly to reflect the
      increasing role of individual equity, safety culture, and stakeholder involvement
      in our modern societies. This report is a consolidation and an evolution of the
      Commission's recommendations concerning the optimisation principle. After some
      background information on the foundation and evolution of the principle, this
      report describes the main characteristics of the process, addresses the issue of
      exposure distribution in that process, and provides the basic requirements for
      its application in operation and regulation. A description of decision-aiding
      techniques commonly used for practical implementation of the optimisation process
      is provided in Annex A.

PMID- 17174717
TI  - Goiter and other iodine deficiency disorders: A systematic review of
      epidemiological studies to deconstruct the complex web.
AB  - A systematic review of the available literature on goiter and other iodine
      deficiency disorders (IDDs) was carried out with the aim of analyzing available
      evidence and providing inputs to the policy makers and program formulators
      regarding the entire issue. The findings point to major issues such as the
      following: methodological issues in epidemiology of goiter and other iodine
      deficiency disorders (IDDs); lacunae in causal linkages; inadequate attention to
      multicausality; flawed assessment of the impact of intervention, i.e., iodized
      salt; and harmful effects of iodine not given due cognizance. Most of the
      research to date has been unidirectional and does not provide comprehensive data
      on all aspects of IDDs. To further compound the issue, many independent
      researchers, on finding something different from the existing dominant paradigm
      (iodized salt as panacea for goiter) have tended to ignore these in their final
      conclusions and recommendations. Thus, evidence from this systematic review
      demonstrates enough basis to start a debate on the entire issue, recognizing
      opposing research findings while continuing with the present strategy. This
      imposes specific problems and necessitates area-specific solutions instead of a
      universal solution, which apart from being less effective may be harmful in the
      long run.

PMID- 17174718
TI  - Reversal effect of thalidomide on established hepatic cirrhosis in rats via
      inhibition of nuclear factor-kappaB/inhibitor of nuclear factor-kappaB pathway.
AB  - BACKGROUND: Suppression of nuclear factor-kappaB (NF-kappaB)/inhibitor of nuclear
      factor-kappaB (IkappaB) signaling pathway is a potential property of thalidomide.
      This study was designed to investigate the effects of thalidomide on expressions
      of NF-kappaB, IkappaB and intercellular adhesion molecule-1 (ICAM-1), and
      vascular cell adhesion molecule (VCAM-1) in established rat liver cirrhosis.
      METHODS: Rat liver cirrhosis was achieved by IP injection of carbon tetrachloride
      (CCl4) three times weekly for 8 weeks. CCl4 was then discontinued and thalidomide
      (100 mg/kg) or its vehicle was administered daily by gavage for 6 weeks.
      Hydroxyproline (HYP) content in liver was detected by biochemical assay. NF
      kappaBp65, ICAM-1, VCAM-1 and alpha-smooth muscle actin (alpha-SMA) protein in
      the liver, IkappaBalpha protein in cytoplasm and NF-kappaBp65 protein in nucleus
      and ICAM-1, VCAM-1 mRNA levels in the liver were studied using
      immunohistochemistry, Western blot, and reverse transcriptase polymerase chain
      reaction, respectively. RESULTS: Compared with the spontaneous recovery of
      cirrhosis, the histopathology of liver of rats given thalidomide was
      significantly improved. HYP content in liver, the expressions of ICAM-1, VCAM-1
      mRNA and protein, NF-kappaBp65 and alpha-SMA protein were decreased significantly
      and IkappaBalpha protein in liver was elevated significantly in this group.
      CONCLUSIONS: Thalidomide may exert its effect on downregulation of NF-kappaB
      induced adhesion molecules and activation of hepatic stellate cell via inhibition
      of degradation of IkappaB to reverse established rat hepatic cirrhosis.

PMID- 17174720
TI  - Inflammation and oxidative stress markers by pentoxifylline treatment in rats
      with chronic renal failure and high sodium intake.
AB  - BACKGROUND: Inflammation is a risk factor for mortality in patients with chronic
      renal failure (CRF). Prevention of extracellular fluid volume expansion and the
      use of certain drugs such as pentoxifylline (PF) may reduce inflammation and
      oxidative stress. The aim of this study is to analyze the effect of dietary
      sodium and PF treatment on the levels of inflammation and oxidative stress
      markers in rats with CRF. METHODS: CRF was induced in rats by 5/6 nephrectomy.
      Different groups of rats with CRF received low sodium (LNa, 0.01% sodium chloride
      [NaCl] in the diet), normal sodium (NNa, 0.05% NaCl in the diet), or high sodium
      diet (HNa, as in NNa plus 0.015% NaCl in the drinking water). An additional group
      received HNa plus PF treatment (25 mg/kg in the drinking water) for 60 days.
      Circulating creatinine, tumor necrosis factor alpha (TNF-alpha), nitrites,
      thiols, malondialdehyde (MDA), and advanced oxidation protein products (AOPP)
      were measured. RESULTS: Higher sodium intake was associated with higher serum
      creatinine levels (median; interquartile range), LNa, 1.255; 0.715, NNa, 1.305;
      0.495, HNa, 2.015; 1.115 mg/dL (p < 0.05), TNF-alpha levels, LNa, 2.7; 23.6, NNa,
      36.7; 47.7, HNa, 263.7; 126.5 pg/mL, and AOPP, LNa, 31.72; 7.55, NNa, 45.89;
      9.38, HNa, 60.41; 37.42 microg/mL. MDA was not modified by sodium intake. PF
      treatment decreased serum TNF-alpha (151.7 pg/mL, p < 0.5) and AOPP (49.83
      micromol/L, p < 0.03), and increased nitrites and thiols levels when compared
      with HNa rats. CONCLUSIONS: High sodium intake increases the serum concentration
      of inflammation and oxidative stress markers; these changes are prevented by PF
      treatment.

PMID- 17174719
TI  - Nitrotyrosine formation and heme oxygenase-1 expression in endotoxemic cirrhotic
      rats.
AB  - BACKGROUND: Endotoxemia increases hepatic toxicity and mortality in cirrhosis.
      Because the mechanism of augmented hepatotoxicity in endotoxemic cirrhotic rats
      is still unclear, we wanted to investigate whether oxidative and nitrosative
      stress play a causative role in lipopolysaccharide (LPS)-treated cirrhotic rats.
      METHODS: Liver cirrhosis was produced by the administration of thioacetamide (0.3
      g/L of tap water) for a period of 3 months in rats. At the end of this period,
      cirrhotic rats were sacrificed 6 h after LPS injection (5 mg/kg,
      intraperitoneally). Serum transaminase activities, plasma total nitrite and
      nitrotyrosine (NT) levels as well as hepatic lipid peroxides, NT formation and
      heme oxygenase 1 (HO-1) expression were determined. RESULTS: LPS administration
      to cirrhotic rats caused further increases in serum transaminase activities, and
      plasma total nitrite and NT levels as well as hepatic lipid peroxide levels as
      compared to cirrhotic rats. Hepatic NT formation and HO-1 expression were also
      found to be increased in LPS-injected cirrhotic rats. CONCLUSIONS: Our results
      indicate that increased oxidative and nitrosative stress may have a synergistic
      effect in LPS-augmented hepatotoxicity in cirrhotic rats.

PMID- 17174721
TI  - IL-1beta induces alkaline phosphatase in human phagocytes.
AB  - BACKGROUND: Alkaline phosphatase (ALPase) is found in blood plasma or serum and
      leukocytes and regulates intercellular processes, maintaining phosphoryl
      metabolites in a steady state, as well as synthesizing and hydrolyzing phosphate
      esters on membranes. ALPase supervises the active transport of inorganic
      phosphates, fats, proteins, carbohydrates and the sodium/potassium pump
      mechanisms. The formed elements of blood such as polymorphonuclear (PMNs)
      leucocytes, macrophages (MP) and some lymphocytes are high in ALPase
      concentrations. METHODS: In this study we have tested whether the interleukin-1
      receptor antagonist (IL-lra) could influence ALPase generation in IL-1beta or
      lipopolysaccharide (LPS)-stimulated neutrophils and MP. Human neutrophils were
      isolated from heparin-anticoagulated blood drawn from healthy individuals by
      centrifugation in a two-step gradient, Ficoll-Hypaque. ALPase activity was
      assessed spectrophotometrically in test tubes containing isolated neutrophils and
      adherence PBMCs treated with LPS, IL-1beta and IL-1ra, alone or in combination.
      RESULTS: IL-lbeta or LPS enhanced ALPase in both PMNs and MP, whereas IL-1ra
      could not inhibit ALPase activity. We performed time course experiments at 0 min,
      5 min, 1 h, 24 h, and 43 h (LPS 20 microg/mL, IL-1beta 10 ng/mL). No significant
      increase in ALPase activity was seen until 1 h; however, there was a rapid rise
      over the next few hours. In another set of experiments using IL-1ra (500 ng/mL),
      there was no difference between treated cells and control cells. The combination
      of IL-1beta plus IL-1ra did not reduce the ability of IL-1beta to induce ALPase
      activity. CONCLUSIONS: These data suggest that IL-1beta stimulates ALPase through
      other mechanisms than the release of arachidonic acid products, which are
      inhibited by IL-lra.

PMID- 17174722
TI  - Tgf-beta antisense therapy increases angiogenic potential in human keratinocytes
      in vitro.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) has been identified as an
      important component of wound healing. Recent developments in molecular therapy
      offer exciting prospects for the modulation of wound healing, specifically those
      targeting TGF-beta. The purpose of this study was to analyze the effect of TGF
      beta targeting on the expression of angiogenic vascular endothelial growth factor
      (VEGF), a key regulator of angiogenesis, and in vitro angiogenic activity.
      METHODS: Expression of angiogenic VEGF in tissue samples from chronic dermal
      wounds was investigated by immunohistochemistry. The effect of TGF-beta targeting
      using antisense oligonucleotides on the expression of VEGF was analyzed by ELISA
      and RT-PCR in cultured human keratinocytes. Human endothelial cells (EC) were
      grown in conditioned medium produced from the treated keratinocytes. EC migration
      was measured using a modified Boyden chamber, EC tube formation was analyzed
      under the light microscope. RESULTS: Immunohistochemical investigation
      demonstrated a decreased expression of VEGF protein in tissue samples from
      chronic dermal wounds compared to normal human skin. Antisense TGF-beta
      oligonucleotide treatment upregulated VEGF secretion in vitro. Addition of
      conditioned medium from TGF-beta antisense-treated keratinocytes resulted in an
      increase of endothelial cell migration and tube formation. CONCLUSIONS: Our
      results demonstrate that TGF-beta antisense oligonucleotide technology may be a
      potential therapeutic option for stimulation of angiogenesis in chronic wounds.

PMID- 17174723
TI  - Changes in extracellular glutamate levels in rat orbitofrontal cortex during
      sleep and wakefulness.
AB  - BACKGROUND: Functional neuroimaging studies have shown that limbic and paralimbic
      areas display increased activity during REM sleep when compared to wakefulness.
      This increase in limbic activity is specific to the REM period of sleep. PET
      scanners do not provide a neurochemical explanation for this increased activity
      during REM sleep. In order to better understand the neurochemical basis of this
      increase, extracellular glutamate levels were measured in the rat orbitofrontal
      cortex during the stages of sleep and wakefulness. METHODS: EEG and EMG activity
      were registered to score the behavioral state in epochs of 15 sec into three
      stages: wakefulness, non-REM sleep and rapid eye movement (REM) sleep. To
      correlate the glutamate concentration of the orbitofrontal cortex with sleep-wake
      states, 1-min dialysate samples were taken and classified as wakefulness, non-REM
      or REM sleep if all four of the 15-sec epochs occurring during the collection of
      that sample and after correction for dead time corresponded to the respective
      state. High-performance liquid chromatography (HPLC) with electrochemical
      detection was used to measure glutamate levels. RESULTS: Glutamate levels of the
      orbitofrontal cortex were increased during REM sleep, diminished during
      wakefulness, and the lowest levels were found during non-REM sleep. CONCLUSIONS:
      These findings demonstrate an increase in the concentration of the excitatory
      neurotransmitter glutamate in the orbitofrontal cortex during REM sleep, which
      could be related to the increased activity in paralimbic structures observed in
      humans using functional neuroimaging, as well as to the proposed role of REM
      sleep on retention of emotional memories.

PMID- 17174724
TI  - IGF-I polymorphism is associated with lean mass, exercise economy, and exercise
      performance among premenopausal women.
AB  - BACKGROUND: We undertook this study to investigate the association of a genetic
      polymorphism of the insulin-like growth factor, IGF-I(189), on body composition,
      exercise performance and exercise economy, after controlling for the independent
      effect of race as assessed by African genetic admixture (AFADM). METHODS: A total
      of 114 premenopausal sedentary women were genotyped for IGF-I189, obtaining
      measures of fat mass, lean body mass, VO2 during cycling and stairclimbing, time
      on treadmill and leg strength. A quantitative value for AFADM was derived from
      genotypic information of approximately 40 ancestry informative markers and used
      as covariate in statistical models. RESULTS: After adjusting for AFADM, IGF-I189
      was negatively associated with lean body mass (p = 0.029) and lean leg mass (p =
      0.050). Leg strength was not associated with the presence/absence of IGF-I189 (p
      = 0.380), but carriers of the allele demonstrated a longer time on the treadmill
      (p = 0.015) after adjusting for AFADM. There was also a negative relationship
      between oxygen uptake during cycling and presence of the IGF-I189 independent of
      AFADM (p = 0.010). CONCLUSIONS: Independent of AFADM, individuals with IGF-I189
      are more likely to have low leg lean mass and to perform better in activities
      requiring exercise economy and endurance performance.

PMID- 17174725
TI  - Heart rate and arrhythmia in patients with psoriasis vulgaris.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory disease involving 1-3% of the
      human population worldwide. Many systemic diseases including cardiovascular
      disturbances have been described in psoriatic patients. However, there is a
      scarcity of data on heart rate, heart rate variability, arrhythmia and conduction
      abnormalities in this group of patients. METHODS: The study comprised 32 patients
      with chronic psoriasis vulgaris and negative personal history of heart problems.
      Severity of the disease was evaluated by Psoriasis Area and Severity Index
      (PASI). Twenty-four-h continuous electrocardiographic monitoring (24-h Holter
      ECG) was performed in all patients. RESULTS: Heart rate was significantly higher
      both during the day and at night in patients with psoriasis vulgaris than in the
      control group (p < 0.0001). There was a positive correlation between the
      increased heat rate, both during the day and at night, in psoriatic patients and
      severity of the disease expressed as PASI. Single supraventricular beats were
      significantly more frequently observed in psoriatic patients vs. the control
      group (p < 0.0001). CONCLUSIONS: An active inflammatory process observed in
      psoriasis seems to exert its influence on increased heart rate and
      supraventricular beats development. However, to confirm the above findings,
      further studies on larger groups of psoriatic patients, presenting different
      types of the disease are mandatory.

PMID- 17174726
TI  - Reduced plasma apelin levels in patients with autistic spectrum disorder.
AB  - BACKGROUND: Dysregulation of the vasopressin (AVP) system has been implicated in
      the pathogenesis of autistic spectrum disorder (ASD). Apelin is a recently
      discovered neuropeptide that could counteract AVP actions and whose receptors are
      colocalized with vasopressin in hypothalamic magnocellular neurons. Aims of the
      present study were to investigate circulating levels of apelin in patients with
      ASD and to assess their correlation with plasma AVP concentrations. METHODS:
      Plasma levels of apelin and AVP were measured in a total of 18 patients with ASD
      and 21 age- and gender-matched healthy comparison subjects. The Childhood Autism
      Rating Scale (CARS) was used to assess the severity of autistic symptoms.
      RESULTS: Significantly reduced levels of apelin (p < 0.001) and elevated
      concentrations of AVP (p = 0.02) were found in ASD patients as compared to
      controls. Additionally, a significant inverse correlation between apelin and AVP
      levels was found within the ASD group (r = -0.61; p = 0.007), but not in healthy
      participants (r = -0.26; p = 0.25). Multivariate linear regression analysis
      showed that only AVP concentrations independently predicted apelin values in ASD
      individuals (beta = -0.42, t = 2.63, p = 0.014). No correlation was seen between
      apelin levels and CARS scores (r = -0.10; p = 0.68). CONCLUSIONS: Our findings of
      a significantly reduced peripheral level of apelin coupled with elevated AVP
      point to a subtle but definite vasopressinergic dysfunction in autism that could
      play a role in the etiopathophysiology of this disorder in humans.

PMID- 17174727
TI  - Severe neurological events following liver transplantation.
AB  - BACKGROUND: Problems related to the central nervous system may have major impact
      on morbidity and mortality. The aim of this retrospective study was to evaluate
      the nature and incidence of serious neurologic events in patients following liver
      transplantation. METHODS: Between January 2001 and May 2004, 168 patients (105
      female, 63 male) requiring transplantation for alcoholic cirrhosis, hepatitis B
      and C, and acute liver failure were admitted to the Intensive Care Unit (ICU) of
      University Hospital Essen after liver transplantation. We identified the reason
      for the neurologic events, the underlying disease, type of immunosuppression, and
      the survival rate. RESULTS: Severe neurologic events occurred in 46 (27.3%) of
      the patients. The length of stay of these patients in the ICU (18.4 +/- 19.7
      days) was longer in comparison to the total patients (8.3 +/- 9.5 days, p <
      0.05). The most common neurological complications were encephalopathy (18.5%) and
      seizures (5.4%). The survival rate after liver transplantation with neurological
      events was lower compared to patients without, but not significantly different
      (73.9 vs. 79.5%). The calcineurin inhibitor used had no impact on neurological
      events [cyclosporine (25.5%); tacrolimus (32.5%)]. CONCLUSIONS: There was a high
      incidence of serious neurologic events after liver transplantation. The major
      neurologic manifestation in our patients was encephalopathy followed by seizures.

PMID- 17174728
TI  - Cardioprotective effect by tumor necrosis factor-alpha and interleukin-6 through
      late preconditioning in unstable angina patients.
AB  - BACKGROUND: It has recently been demonstrated that upregulation of
      proinflammatory cytokines plays an important role in induction of the late
      preconditioning in rodent models. The aim of this study was to determine if there
      was a late preconditioning effect caused by higher proinflammatory cytokines in
      unstable angina patients. METHODS: TNFalpha and IL-6 levels in plasma before
      surgery were determined by an enzyme-linked immunosorbent assay. Biopsies of
      right atrial tissue were obtained from patients with unstable and stable coronary
      artery disease in conjunction with coronary artery bypass surgery. The two main
      transcription factors involved in the late preconditioning nuclear factor kappaB
      (NFkappaB), signal transducer and activator of transcription 3 (STAT3) were
      investigated by electromobility shift assay. The effector proteins in late
      preconditioning including inducible nitric oxide synthase (iNOS), cyclooxygenase
      2 (COX-2) were evaluated by immunoblotting as candidates for possible endogenous
      cardioprotective agents. Cardioprotective effects were assessed by creatine
      kinase MB (CK-MB) and cTnT leakage postoperatively. RESULTS: We found parallel
      relationships between plasma cytokine levels, activated extent of transcription
      factors, expression quantities of effector proteins, and cardioprotective effects
      assessed by CK-MB and cTnT. CONCLUSIONS: Upregulation of the proinflammatory
      cytokines in plasma by unstable angina induces late preconditioning effects and
      shifts the myocardium to a preconditioned phenotype upon exposure to impending
      stress.

PMID- 17174729
TI  - Effect of balneotherapy on the antioxidant system--a controlled pilot study.
AB  - BACKGROUND: Balneotherapy is among the most widely used modalities of physical
      therapy in countries rich in mineral waters. This trial was intended to ascertain
      whether balneotherapy (i.e., therapeutic bath in mineral water) has any influence
      on the antioxidant system and whether there are any differences compared to
      bathing in tap water. METHODS: The ten subjects in Group I bathed in alkaline
      thermal water, Group II used alkaline, chlorine-containing mineral water, whereas
      Group III bathed in tap water. Catalase, superoxide dismutase, malondialdehyde
      protein and glutathione peroxidase levels were measured at baseline and after
      concluding the course of balneotherapy. RESULTS: Balneotherapy with either of the
      two mineral waters reduced the activity of all four enzymes studied. Using tap
      water, however, had no influence on either catalase or superoxide dismutase
      activity after one session or glutathione peroxidase levels after a course of ten
      balneotherapy treatments. CONCLUSIONS: Thermal water may have a beneficial effect
      on the formation of free radicals. The therapeutic efficacy of mineral vs. tap
      water is different, although bathing in hot water itself reduces enzyme activity.

PMID- 17174730
TI  - Contemporary treatment and outcomes of zygomycosis in a non-oncologic tertiary
      care center.
AB  - BACKGROUND: Zygomycosis is an emerging mycosis of increasing relevance. Limited
      data exist for outcomes with contemporary therapies. METHODS: A 6-year
      retrospective chart review was performed in a non-oncological tertiary care
      center for patients with zygomycosis. RESULTS: Sixteen episodes of proven
      (EORTC/MSG criteria) zygomycosis were identified. The average age was 49.2 years.
      Sites of infection were surgical/traumatic wound [5], rhinocerebral [4],
      disseminated [2], pulmonary [2], peritoneal [2], and localized skin [1].
      Associated conditions included diabetes [7], ketoacidosis [2], end-stage renal
      disease [4], surgery/trauma [4], steroids [3], solid organ transplant [2],
      neutropenia [1], and intravenous drug use [1]. Twelve patients had surgical
      debridement. Medical therapy included liposomal amphotericin B, conventional
      amphotericin B (CAB), and amphotericin B lipid complex. Overall mortality was
      4/16 (25%), occurring in a patient each with rhinocerebral, pulmonary, surgical
      wound infection, and disseminated disease. Mortality with surgical treatment was
      2/12 (17%) vs. 2/4 (50%) without surgery. Mortality for patients treated with CAB
      was 1/3 vs. 3/12 for those treated with any lipid preparation. Serious morbidity
      occurred in 7/12 survivors. CONCLUSIONS: In this limited study of contemporary
      therapies, patients with zygomycosis from a non-oncological tertiary care center
      have lower mortality than classically described. This disease and its treatments
      are still associated with severe morbidity, disfigurement, and disability.

PMID- 17174731
TI  - Erythrocyte oxidative damage in chronic fatigue syndrome.
AB  - BACKGROUND: It has been hypothesized that a link exists between erythrocyte
      metabolism (particularly redox metabolism) and erythrocyte shape and that both
      are related to erythrocyte deformability. The aim of this research is to confirm
      the results of earlier studies and to investigate a correlation between
      erythrocyte morphology and erythrocyte oxidative damage in chronic fatigue
      syndrome (CFS). METHODS: Reduced glutathione (GSH), malondialdehyde (MDA),
      methemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) were measured in
      31 patients suffering from CFS and 41 healthy control subjects. Scanning electron
      microscopic studies of the erythrocytes from both groups were also carried out.
      RESULTS: There was evidence of oxidative damage in CFS with statistically
      significant increases in 2,3-DPG (p < 0.05), metHb (p < 0.005) and MDA (p <
      0.01). The CFS patients in this study also had significantly more stomatocytes in
      their blood than the normal subjects (p < 0.005). CONCLUSIONS: There is a strong
      likelihood that the increase in erythrocyte antioxidant activity is associated
      with the presence of stomatocytes. The results of this study provide further
      evidence for the role of free radicals in the pathogenesis of CFS and a link
      between erythrocyte metabolism and erythrocyte shape.

PMID- 17174732
TI  - Correlation between asthma severity and serum IgE in asthmatic children
      sensitized to Dermatophagoides pteronyssinus.
AB  - BACKGROUND: We undertook this study to test the possible correlation between
      serum concentration of total and specific IgE antibodies and asthma severity in
      asthmatic children sensitized to the house dust mite Dermatophagoides
      pteronyssinus. METHODS: The study included 157 asthmatic children aged 5-15 years
      (8 +/- 3 years). Clinical diagnosis was based on personal and family history,
      physical examination, pulmonary function testing and skin tests. Asthma severity
      was determined according to GINA guidelines. In vitro tests included serum
      concentration of total and specific IgE. RESULTS: All asthmatic children had
      elevated serum concentration of total IgE. The children with elevated serum
      concentration of total IgE also showed an increased serum concentration of
      specific IgE. Asthma of higher higher severity was present in patients with total
      IgE concentration >288.0 kIU/L (AUC = 0.736) and specific IgE to Dermatophagoides
      pteronyssinus >44.1 kIUA/L (AUC = 0.843). Intermittent asthma was present in
      76.9% of children with specific IgE concentration <44.1 kIUA/L. The positive
      predictive value suggested with 79.2% probability that a child with a
      concentration of specific IgE to Dermatophagoides pteronyssinus >44.1 kIUA/L
      would have a more severe form of asthma. CONCLUSIONS: Asthmatic children with
      higher asthma severity have a higher serum concentration of both total IgE
      (>288.0 kIU/L) and specific IgE to Dermatophagoides pteronyssinus (>44.1 kIUA/L),
      respectively.

PMID- 17174733
TI  - Quantitative analysis of lymphangiogenic markers in human gastroenteric tumor.
AB  - BACKGROUND: Lymphatic spread of gastroenteric tumor cells to regional lymph nodes
      is one of the early events in metastatic cancers and is often associated with
      distant metastatic spread and poor prognosis. Expression levels of newly
      described lymphatic endothelial markers, LYVE-1, VEGF-C, VEGF-D and the VEGF
      receptors VEGFR-3 were assessed in our study. METHODS: Paired (tumor and
      corresponding normal tissue) samples were obtained. The expression level of each
      factor was determined using RT-PCR and quantified by using a real-time
      quantitative PCR (RT-QPCR) technique, with respective cloned cDNA plasmids as
      internal standards. RESULTS: The expression of VEGF-C and lymphatic endothelial
      marker VEGFR-3 was significantly greater in patients with lymph node metastasis
      than in those without metastasis, but no different expression level of VEGF-D and
      LYVE-1 was detected in both groups of patients. Lymphatic vessel density (LVD),
      which was assessed by immunohistochemistry for LYVE-1, was correlated with
      lymphangiogenesis factors and lymph node metastasis. Expression of VEGF-C and
      VEGFR-3 was significantly associated with higher peritumoral LVD than normal
      group, and LVD was found greater in the node-positive group than in the node
      negative group. CONCLUSIONS: These results indicate that quantitative analysis of
      lymphangiogenic marker VEGF-C and VEGFR-3 in gastroenteric specimens may be
      useful in predicting metastasis of gastroenteric cancer to regional lymph nodes,
      but the role of LYVE-1 in predicting metastasis of gastroenteric cancer requires
      further analysis.

PMID- 17174734
TI  - Test-retest reliability of heart rate variability and respiration rate at rest
      and during light physical activity in normal subjects.
AB  - BACKGROUND: A variable that remains stable over repeated measurements (in stable
      conditions) is ideal for tracking modifications of the clinical state. The aim of
      the present study is to examine test-retest reliability of time-domain heart rate
      variability and respiration rate measurements using a portable device on normal
      subjects during rest and light physical activity. METHODS: Twenty-six normal
      subjects [18 females and 8 males aged 28 +/- 6 years and 34 +/- 12 years (mean +/
      SD), respectively] underwent two measurements for time-domain heart rate
      variability (SDNN and RMSSD) and respiration rate, with 7 days in between.
      Measurements took place under three conditions: lying down in a laboratory,
      cycling in a laboratory and sleeping in an ambulatory surrounding. Reliability
      was assessed statistically by calculating intra-class correlation coefficients
      (ICC). RESULTS: Reliability was found to be good to excellent for both time
      domain heart rate variability (SDNN: ICC values between 0.74 and 0.85, RMSSD: ICC
      values between 0.75 and 0.98) and for respiration rate (ICC values between 0.77
      and 0.96). CONCLUSIONS: Both time-domain heart rate variability and respiration
      rate can be reliably assessed. However, we advise reliability research in a
      clinical setting before using the device for tracking modifications in a clinical
      state.

PMID- 17174735
TI  - Relationship of cardiovascular risk factors and serum ferritin with C-reactive
      protein.
AB  - BACKGROUND: Serum iron plays an important role in the oxidation of low-density
      lipoprotein (LDL) cholesterol, it induces inflammatory reactions and it is
      positively related to coronary heart disease. An increase of the inflammatory
      marker, C-reactive protein (CRP), is a risk factor for future cardiac events.
      Hence, we examined the association of the cardiovascular disease risk factors and
      serum ferritin with CRP. METHODS: This study was performed on 808 subjects (465
      males and 343 females). CRP levels >3.0 mg/L, serum ferritin levels >200 ng/mL,
      total cholesterol levels >200 mg/dL and LDL-cholesterol levels >160 mg/dL were
      all considered as elevated. High-density lipoprotein cholesterol levels <40 mg/dL
      were considered as low. RESULTS: In the group with low LDL-cholesterol, no
      correlation was detected between serum ferritin and hsCRP [odds ratio (OR) =
      1.68, 95% confidence interval (CI) = 0.81-3.48, p = 0.144]. However, a
      correlation was detected in the group with elevated LDL-cholesterol (OR = 11.21,
      95% CI = 1.14-110.27, p = 0.032). In addition, when the interaction term was
      added to the assessment of the correlation between the elevated hsCRP and LDL
      cholesterol, the strong correlation of hsCRP and serum ferritin was confirmed (p
      = 0.002). CONCLUSIONS: Oxidation of LDL-cholesterol by serum ferritin may play a
      role in the inflammatory reaction and for the increased hsCRP. Future prospective
      studies may be required to assess whether reducing the serum ferritin and CRP
      levels via medical intervention and life style modification would be helpful for
      preventing cardiovascular disease.

PMID- 17174736
TI  - Multislice CT-angiography in percutaneous postinterventional hematuria and kidney
      bleeding: Influence of diagnostic outcome on therapeutic patient management.
      Preliminary results.
AB  - BACKGROUND: The aims of this study were to assess the value of multislice CT
      angiography (MS-CT-A) in percutaneous postinterventional kidney bleeding and to
      determine the influence of diagnostic outcome on therapeutic patient management.
      A recommendation for the interdisciplinary patient work-up for the emergency room
      was offered. METHODS: Between April 2003 and January 2006, 12 patients with
      hematuria and clinically suspected renal bleeding underwent MS-CT-A for emergency
      diagnostic assessment. The spectrum of kidney injuries on CT was analyzed
      according to an organ-scaling scheme. The efficacy of MS-CT-A with regard to
      confirmation of active arterial bleeding was evaluated as well as the therapeutic
      consequences for patient management. RESULTS: In seven patients (59%) staged
      grade V renal injury, active renal arterial bleeding was detected on CT-A.
      Patients immediately underwent therapeutic angiography with confirmation of
      arterial bleeding and successful embolization. Four patients (33%) were staged
      grade I renal injury with subcapsular kidney hematoma but no active hemorrhage.
      Therefore, these patients were not exposed to further therapeutic intervention.
      One patient (8%) was diagnosed grade II renal injury with superficial cortical
      renal parenchyma tear and no active bleeding on CT-A. CONCLUSIONS: MS-CT-A is a
      valuable, fast and objective emergency tool for assessment of postinterventional
      renal hemorrhage. Detection of contrast material extravasation to affirm ongoing
      arterial bleeding and to localize bleeding site at the level of segmental or
      interlobar renal artery is a predictor for the need for further treatment and
      justifies therapeutic radiological or surgical management.

PMID- 17174737
TI  - Take on the "welcome to Medicare" exam challenge and create the sequel.

PMID- 17174738
TI  - Oral solid potassium chloride and anticholinergic medications: a new drug
      interaction for an old drug?

PMID- 17174739
TI  - "You need how many months of bank statements?!" Medicaid long-term care
      eligibility changes after the DRA.

PMID- 17174740
TI  - Linking theory and gerontological nursing practice in senior housing.
AB  - This article illustrates the use of 2 theoretical models in planning and
      implementing health programs in senior housing. The Person-Environment Fit Model,
      developed by Lawton, and the Transitions Theory, developed by Meleis and
      colleagues, form the basis for understanding the interaction between people and
      their environments through transitions common in late life. The models and their
      application to practice are described, with examples at the individual, group,
      and community levels. Implications and future directions are identified for the
      use of such models in gerontological nursing practice.

PMID- 17174741
TI  - Optimizing undergraduate nursing education: demystifying care of older adults in
      the home setting.
AB  - It is a challenge to provide experiences for nursing students that allow them to
      experience a professional relationship with older adults in the home setting.
      Home health agencies are under pressure related to productivity demands and may
      not provide preceptored experiences for students. Nursing students may not know
      any older adults outside of the institutional setting and consequently may have
      many misconceptions about what is and is not normal aging. This article describes
      an undergraduate nursing class and the out-of-classroom assignments that
      increased student understanding of nursing practice in the home, the effects of
      the home environment on the care of older adults, and the experiences of older
      adults living in the community. This article has relevance to nurses because it
      is important that we participate in creative methods of teaching students to
      value older adults and how to care for them in the community.

PMID- 17174742
TI  - Dropping the bomb: the experience of being diagnosed with Parkinson's disease.
AB  - This qualitative descriptive study examined the advice people with Parkinson's
      disease have for someone newly diagnosed. Qualitative content analysis of
      interview data from 11 persons with Parkinson's resulted in 1 major theme:
      "Dropping the Bomb." This theme signified sorting through the rubble and picking
      up the pieces of lives shattered by the diagnosis. Four subthemes emerged:
      Guarded Anticipation, Becoming Informed, Disease Dynamics, and Negotiating with
      Mr. Parkinson. In planning and implementing interventions, nurses might ease the
      impact of the diagnosis and the context of the disease if they contextualize
      their interventions within the preferences of the persons living with it.

PMID- 17174743
TI  - The empowerment of older mothers and daughters: rehabilitation strategies
      following a hip fracture.
AB  - Empowerment was a major concept that emerged from a grounded theory study of 6
      older mother-daughter dyads when the mother experienced a hip fracture. Modeling
      courage and sharing ideas were key components of empowerment. Modeling courage
      enabled mothers and daughters to retain strength in the face of pain and
      difficulties. Sharing ideas involved suggestions about physical rehabilitation,
      ways to access medical and legal information, as well as life philosophies. In
      this article, the process of empowerment is described. Recommendations are made
      to improve the lives of older women and their daughters during and after a hip
      fracture.

PMID- 17174744
TI  - T-cell receptor triggering differentially regulates bim expression in human
      lymphocytes from healthy individuals and patients with infectious mononucleosis.
AB  - Bim, a proapoptotic member of the Bcl-2 protein family, is a major regulator of
      central and peripheral T-cell deletion. Regulation of Bim activity by T-cell
      receptor (TCR) triggering is not well understood. We investigated expression of
      Bim in different subpopulations of ex vivo isolated human T cells from healthy
      donors and patients with infectious mononucleosis (IM). Upregulation of Bim
      expression in response to TCR-triggering was observed only in a small proportion
      of analyzed samples of peripheral blood lymphocytes (PBLs) from healthy donors
      and only occasionally upon longitudinal analysis of cells isolated from the same
      individuals. Populations of naive or memory T cells enriched on the basis of
      CD45RO or CD45RA expression showed only slight and comparable Bim upregulation.
      In contrast, ex vivo isolated PBLs from IM patients in the acute stage of the
      disease with significant expansions of CD8+ cells expressed increased levels of
      Bim, and lymphocytes from the majority of analyzed IM patients exhibited
      significant upregulation of all major Bim isoforms in response to TCR triggering.
      These results demonstrate that at least some antigen-induced expansions of human
      CD8+ T cells are associated with increased levels of Bim, and TCR triggering in
      effector T lymphocytes may increase Bim activity by upregulation of its
      expression.

PMID- 17174745
TI  - Role of tonsillar IgD+CD27+ memory B cells in humoral immunity against
      pneumococcal infection.
AB  - IgD+CD27+ memory B cells are a major compartment of circulating memory B cells.
      However, the characteristics of these cells in the tonsils have been unclear. In
      this study, IgD+CD27+ memory B cells residing in the tonsillar marginal zone were
      found to exhibit similar characteristics as IgD+CD27+ memory B cells in the
      periphery, namely large morphology, expression of surface molecules, and
      hypermutated Ig variable region genes. Furthermore, these IgD+CD27+ memory B
      cells predominantly produced IgM, including IgM specific against pneumococcal
      polysaccharides. Taken together, these results provide convincing evidence that
      tonsillar IgD+CD27+ memory B cells impart protective humoral immunity against
      pneumococcal infection by producing high-affinity IgM.

PMID- 17174746
TI  - Human bone marrow stromal cells hamper specific interactions of CD4 and CD8 T
      lymphocytes with antigen-presenting cells.
AB  - Bone marrow stromal cells (BMSCs) may inhibit T-cell functions in vitro and thus
      have been proposed as immunoregulators to control in vivo graft-versus-host
      disease (GVHD) in haploidentical hemopoietic stem cell transplants. To better
      investigate this phenomenon, we used a defined experimental system in which
      responding T cells are antigen-specific and devoid of alloreactivity against BMSC
      from a different subject. Thus, we established antigen-specific human CD4 and CD8
      T-cell lines as the readout system. Antigen-dependent proliferation was reduced
      with both T-cell subsets cultured on confluent BMSCs, and also on confluent human
      skin fibroblasts (HSF) inhibited T-cell proliferation with similar efficiency.
      Morphological observations of the cocultures showed impairment of physical
      interactions between T-cell and antigen-presenting cells in the presence of BMSC,
      with lack of formation of antigen-dependent clusters of T cells and antigen
      presenting cells (APCs). In contrast, no effects were seen with BMSC-conditioned
      medium. Since suppression was seen only with confluent mesenchymal cells, this
      phenomenon may not be relevant in vivo, where BMSCs are at low frequency. In
      addition, if the reported suppressive effect of BMSCs on GVHD in vivo is
      confirmed, a different in vitro system should be envisaged to better understand
      and exploit the underlying mechanism.

PMID- 17174747
TI  - Investigation of KIR gene frequencies in type 1 diabetes mellitus.
AB  - The frequency of killer immunoglobulinlike receptors (KIR) genes was examined in
      type 1 diabetes mellitus patients and controls from Finland. The KIR gene 2DS5
      was significantly decreased in patients versus controls, but this was no longer
      significant after correction for the number of comparisons made.

PMID- 17174748
TI  - The association between mannose-binding lectin gene polymorphism and rheumatic
      heart disease.
AB  - Mannan-binding lectin (MBL) is an innate pattern recognition molecule known to
      play a key role in pathogen clearance. As MBL2 gene polymorphism is associated to
      an increased susceptibility to infection, we aimed to determine genetic
      variations in the MBL2 gene in rheumatic heart disease (RHD). Genetic variations
      in the promoter and exon 1 region of the MBL2 gene were analyzed in 107 patients
      with RHD and 105 controls by real-time polymerase chain reaction. The frequency
      of MBL2* A/A genotype was significantly higher in RHD patients (71/107, 66.36% vs
      52/105, 49.52%, p<or=0.02, OR=1.99, 95% CI, 1.15-3.50). A/A genotypes were
      associated with higher levels of MBL in RHD compared with controls with the same
      genotype (p<or=0.004). The frequency of HYPA/HYPA, HYPA/LYQA, and LYQA/LYQA
      haplotypes was also increased in RHD (p<or=0.03, OR=1.98, 95% CI, 1.05-3.73).
      However, the frequency of MBL2 variant alleles (termed "O") was lower among
      patients (39/214, 18.2% vs 63/210, 30.0%, p<or=0.006, OR=0.52, 95% CI, 0.33
      0.82), which was also seen for O/O genotypes (3/107, 2.8% vs 10/105, 9.5%,
      p<or=0.05, OR=0.27, 95% CI, 0.07-1.03). This data suggests a role for MBL
      genotypes in the susceptibility to RHD. However, it still remains unclear whether
      A/A homozygosity is a risk factor for RHD or rheumatic fever itself.

PMID- 17174750
TI  - MICA A8: a new allele within MHC class I chain-related A transmembrane region
      with eight GCT repeats.
AB  - Analysis of the MICA gene revealed a trinucleotide repeat (GCT) microsatellite
      polymorphism within the transmembrane region. So far, seven alleles of the exon 5
      of the MICA gene, which consist of 4, 5, 6, 7, 9, and 10 repetitions of GCT or
      five repetitions of GCT with an additional nucleotide insertion (GGCT), have been
      identified. These alleles have been accordingly named A4, A5, A6, A7, A9, A10,
      and A5.1, and the sizes are, respectively, 179 bp, 182 bp, 186 bp, 189 bp, 194
      bp, 197 bp, and 185 bp. We analyzed 1100 Italian subjects for MICA exon 5
      microsatellite polymorphism. A new peak corresponding to 191-bp size was observed
      in one individual, and we confirmed the presence of new polymorphism in exon 5 by
      sequencing, which consisted of eight GCT repeats. We named this allele, as a
      current nomenclature, MICA8.

PMID- 17174749
TI  - Linkage disequilibrium with predisposing DR3 haplotypes accounts for apparent
      effects of tumor necrosis factor and lymphotoxin-alpha polymorphisms on type 1
      diabetes susceptibility.
AB  - Tumor necrosis factor (TNF) and lymphotoxin alpha (LT-alpha) are immunomodulators
      that have been hypothesized to contribute to susceptibility to type 1 diabetes
      (T1D). Several polymorphisms in the TNF and LT-alpha loci have been extensively
      studied for T1D association, with conflicting reports. In this study, we examined
      two TNF variants and one LT-alpha variant for T1D association in 283 Caucasian,
      multiplex T1D families for which complete human leukocyte antigen (HLA)
      genotyping data are available. Initially, association with T1D was seen for LT
      alpha A1069G (intron A, p=0.011, rs909253) and TNF G(-308)A (p<1x10(-5),
      rs1800629), but no association was observed for TNF G(-238)A (rs361525). After
      adjusting the data for linkage disequilibrium (LD) with DRB1-DQB1 haplotypes,
      however, only one polymorphism, TNF G(-238)A showed significant association with
      T1D (p<0.006). When HLA-DR3 haplotypes were examined, the A allele of TNF G(
      238)A was significantly overtransmitted to affected offspring (p<0.009).
      Including HLA-B data in the analysis revealed that TNF (-238)A is present
      exclusively on DR3 haplotypes that also carry HLA-B18. Transmission proportion of
      B18-DR3 haplotypes did not differ between those with TNF (-238)A and those with
      TNF (-238)G. Thus, variation at TNF does not affect the T1D risk for B18-DR3
      haplotypes, and the apparent association of TNF(-238)A with T1D may simply
      reflect its presence on a high-risk haplotype.

PMID- 17174755
TI  - The need for national patient safety goals for ambulatory oral and maxillofacial
      surgery.

PMID- 17174758
TI  - Upregulation of serum and tissue vascular endothelial growth factor correlates
      with angiogenesis and prognosis of oral squamous cell carcinoma.
AB  - PURPOSE: To investigate both serum vascular endothelial growth factor (VEGF)
      concentrations and VEGF expression in patients with oral squamous cell carcinoma
      (OSCC), and to clarify whether upregulation of VEGF in OSCC patients is
      associated with increased microvessel density and various clinicopathologic
      features of patients with OSCC. PATIENTS AND METHODS: The study population
      included 31 patients with OSCC and 10 normal individuals. Concentration of serum
      VEGF was determined by using an ELISA kit. Immunohistochemistry was used to
      evaluate VEGF expression and microvessel density in OSCC. RESULTS: Our results
      showed that both serum VEGF levels and VEGF positivity were closely associated
      with both regional lymph node status and clinical stage of patients with OSCC.
      Increased microvessel density in oral cancer tissues was significantly higher in
      VEGF-positive tumors than VEGF-negative tumors. CONCLUSION: Our present study
      indicated that upregulation of VEGF in oral cancer was correlated with both tumor
      angiogenesis and disease severity.

PMID- 17174759
TI  - Anatomical study of accessory nerve innervation relating to functional neck
      dissection.
AB  - PURPOSE: The present study sought to clarify correlations of accessory nerve
      innervation in the neck region and innervation of the sternocleidomastoid and
      trapezius muscles with postoperative dysfunction after functional neck dissection
      by macroscopic observation. MATERIALS AND METHODS: The materials used in this
      study were 35 cadavers provided for anatomical practice to the Department of
      Anatomy, Tokyo Dental College. The accessory nerve was identified at the anterior
      margin of the trapezius muscle, and its innervation in the posterior triangle of
      the neck was examined in detail. RESULTS: The superficial cervical vein
      vascularizes the anterior margin of the trapezius muscle near an area where the
      main trunk of the accessory nerve innervates the trapezius muscle. The results
      showed 3 types of accessory nerve innervation of the sternocleidomastoid muscle:
      Type A, the not penetrating type; Type B, the partially penetrating type; and
      Type C, the completely penetrating type. In addition, 5 types of innervation of
      the trapezius muscle by the main trunk and branches of the accessory nerve were
      apparent, with the number of branches innervating the muscle ranging from 0 to 4.
      CONCLUSIONS: Dysfunction after functional neck dissection can thus be avoided by
      paying attention to not only the main trunk of the accessory nerve, but also the
      branches. Moreover, when identifying accessory nerve innervation of the trapezius
      muscle, the superficial cervical vein may offer a useful surgical landmark.

PMID- 17174751
TI  - Group-specific amplification of cDNA from DRB1 genes. Complete coding sequences
      of partially defined alleles and identification of the new alleles DRB1*040602,
      DRB1*111102, DRB1*080103, and DRB1*0113.
AB  - We present here the complete coding sequences, previously unavailable, of the
      DRB1 alleles DRB1*030102, *0306, *040701, *0408, *1327, *1356, *1411, *1446,
      *1503, *1504, *0806, *0813, and *0818. For cDNA isolation, new group-specific
      primers located at the 5'UT and 3'UT regions were used to carry out allele
      specific amplification and a convenient method for determining full-length
      sequences for DRB1 alleles. Complete coding sequencing of samples previously
      typed as DRB1*0406, DRB1*080101, and DRB1*1111 revealed new alleles with
      noncoding nucleotide changes at exons 1 and 3. In addition, we found a novel
      allele, DRB1*0113, whose second exon carries a sequence motif characteristic of
      DRB1*07 alleles. The predicted class II haplotypic associations of all alleles
      are reported and discussed.

PMID- 17174757
TI  - Hemodynamic stability in medically treated hypothyroid patients undergoing
      intravenous sedation.
AB  - PURPOSE: To evaluate the hemodynamic stability of medically treated hypothyroid
      patients undergoing intravenous sedation for dentoalveolar surgery. PATIENTS AND
      METHODS: A retrospective chart analysis of 20 consecutive white male patients
      actively being treated for hypothyroidism undergoing intravenous sedation for
      dentoalveolar surgery. Twenty consecutive normothyroid white male patients
      undergoing intravenous sedation for dentoalveolar surgery were used as controls.
      Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
      blood pressure (MAP), pulse pressure (PP), peripheral oxygen saturation
      (S(p)O(2)) and pulse were recorded at 5-minute intervals during intravenous
      sedation. RESULTS: Statistically significant lower average hemodynamic values
      were seen in hypothyroid patients compared to normothyroid patients in SBP (P =
      .05) and PP (P = .003). There were highly significant baseline changes for
      hypothyroid patients in DBP (P < .001) and MAP (P < .001) and significant
      baseline changes for normothyroid patients in DBP (P = .03), PP (P = .02) and
      pulse (P = .03). All changes were maintained within +/- 10% of baseline (range, 
      8.9% to +9.6%). CONCLUSIONS: Intravenous sedation for dentoalveolar surgery in
      medically treated hypothyroid patients maintains hemodynamic stability.

PMID- 17174760
TI  - The posterior segment of the temporomandibular joint capsule and its anatomic
      relationship.
AB  - PURPOSE: The aim of this work was to clarify the arrangement of the posterior
      segment of the temporomandibular joint capsule and its pertinent relationships.
      MATERIALS AND METHODS: The temporomandibular region was dissected bilaterally in
      20 adult cadavers. Natural stained latex was injected into 16 cadavers through
      the external carotid artery to facilitate the dissection of the arterial vessels.
      RESULTS: The posterior segment of the joint capsule is made up of the so-called
      "bilaminar zone" of the articular disc. The upper internal portion of the
      posterior segment of the capsule was reinforced by the discomalleolar ligament.
      The retroarticular space was filled with loose connective tissue and the anterior
      branches of the anterior tympanic artery were distributed throughout the
      posterior segment of the joint capsule. CONCLUSION: The posterior segment of the
      temporomandibular joint capsule corresponds to the bilaminar zone of the
      articular disc. The structures of the retroarticular space are extracapsular.

PMID- 17174756
TI  - Three-dimensional changes in upper airways of patients with obstructive sleep
      apnea following maxillomandibular advancement.
AB  - PURPOSE: The purpose of this study was to analyze the morphologic changes of the
      airway in obstructive sleep apnea (OSA) patients by helical computed tomography
      (CT) scanning following maxillomandibular advancement (MMA) surgery. MATERIALS
      AND METHODS: Twenty consecutive OSA patients treated with MMA from 2000 to 2003
      at the University of Alabama at Birmingham Hospital and diagnosed by
      polysomnography (PSG) were included in this study. The criteria for this study
      were MMA surgery, pre- and postoperative helical CT scan, and PSG. Lateral (LAT)
      and anterioposterior (AP) airway dimensions were measured from the level of the
      hard palate to the hyoid using helical CT scans. RESULTS: There was enlargement
      of LAT and AP diameters for all patients at all levels. LAT dimensions were
      enhanced greater than AP in the retroglossal region. CONCLUSION: MMA results in
      significant increase in both AP and LAT airway dimensions.

PMID- 17174763
TI  - Lack of association between proliferative verrucous leukoplakia and human
      papillomavirus infection.
AB  - PURPOSE: To analyze proliferative verrucous leukoplakia (PVL) for the presence of
      human papillomavirus (HPV) in different stages of the disease. MATERIALS AND
      METHODS: We studied 13 patients with PVL. In 10 patients (76.9%), a lesional
      biopsy was taken and frozen at -40 degrees C. Four patients were instructed to
      mouth rinse with sterile sera. The biopsy and rinse samples were analyzed for HPV
      by PCR. RESULTS: We did not detect HPV infection in the PVL tissue or in the oral
      rinse of any of the 13 patients in any stage of the disease analyzed, neither in
      oral squamous cell carcinoma nor in the simple hyperkeratosis. CONCLUSION: There
      was no association between PVL and HPV infection in our patients.

PMID- 17174762
TI  - Drug treatment of trigeminal neuralgia: a systematic review of the literature.
AB  - PURPOSE: This study undertook a systematic review of the literature on drug
      treatment of trigeminal neuralgia. METHODS: An electronic search was carried out
      for articles published between January 1960 to February 2005. Studies with high
      level of evidence were included. The levels of evidence of the articles were
      classified after the guidelines of the Oxford Centre for Evidence-Based Medicine.
      RESULTS: Of 770 publications, only 21 publications showed a high level of
      evidence (6 randomized controlled trials and 15 clinical trials/controlled
      clinical trials), with a total of 348 patients. A total of 749 publications were
      not included in the review as they showed a low level of evidence. CONCLUSIONS:
      Anticonvulsants are effective in treating trigeminal neuralgia; however, few
      studies with high levels of evidence were found. It is quite difficult to compare
      or even combine their outcomes in a scientifically meaningful manner. Due to
      insufficient research data, there is a need for high-quality randomized
      controlled trials in this area of medicine.

PMID- 17174766
TI  - Temporomandibular joint internal derangement and osteoarthrosis: are effusion and
      bone marrow edema prognostic indicators for arthrocentesis and hydraulic
      distention?
AB  - PURPOSE: Arthrocentesis and hydraulic distention of the temporomandibular joint
      (TMJ) has proven to be an effective modality in treating patients exhibiting
      clinical findings consistent with the diagnosis of disc displacement without
      reduction. The purpose of this study was to investigate whether the magnetic
      resonance imaging (MRI) variables of effusion and/or bone marrow edema may
      predict treatment outcomes of arthrocentesis and hydraulic distention of the TMJ.
      PATIENTS AND METHODS: The study group comprised 37 consecutive patients with TMJ
      pain, who were assigned a unilateral clinical TMJ disorder of TMJ pain associated
      with an internal derangement (ID) type III (disc displacement without reduction)
      and a TMJ pain side-related MRI diagnosis of disc displacement without reduction
      associated with osteoarthrosis (OA). Bilateral sagittal and coronal MRI images
      were obtained immediately before the operation to establish the presence or
      absence of ID, OA, TMJ effusion, and bone marrow edema. Pain level and mandibular
      range of motion (ROM) were assessed preoperatively and compared with the
      respective 2-month follow-up findings. Outcome criteria for success were a ROM
      >or=35 mm and pain reduction >50%. A logistic regression analysis was used to
      compute the odds ratio for TMJ effusion and bone marrow edema for successful
      outcomes (n = 21) versus unsuccessful (n = 16) outcomes. RESULTS: At the 2-month
      follow-up, clinical evaluation showed a significant reduction in TMJ pain during
      function (P = .000), a significant reduction in clinical diagnoses of TMJ
      disorders (P = .016), and a significant increase in ROM (P = .000). A significant
      increase in the risk of an unsuccessful outcome of ROM <35 mm and/or pain
      reduction >or=50% occurred with MRI findings of effusion (odds ratio 1:10.8 =
      0.09; P = .007). CONCLUSIONS: TMJ effusion may prove to be an important
      prognostic determinant of successful arthrocentesis. However, the data re
      emphasize the concept that the prediction of a specific outcome is not a matter
      of simple linearity, in which the presence of 1 factor may equate with predictive
      ability, but rather is a function of a complex interaction among different
      biological variables.

PMID- 17174764
TI  - Transverse displacement of the proximal segment after bilateral sagittal split
      osteotomy advancement and its effect on relapse.
AB  - PURPOSE: To evaluate the transverse displacement of the proximal segment and its
      association with horizontal relapse post-treatment. METHODS: Retrospective study
      of 25 patients (10 males, 15 females) who underwent bilateral sagittal split
      osteotomy (BSSO) advancement and Le Fort I osteotomy with rigid internal fixation
      (RIF) using bicortical lag screws. Posteroanterior and lateral cephalograms
      obtained preoperatively (T1), early postoperatively (T2), and after orthodontic
      treatment completion (T3) were used to assess: the angulation of each proximal
      segment relative to the upper orbital margin line and obtain the sum of both
      angles (total angle), mandibular intergonial width (IGW), mandibular length (Ar
      B), B point position, and condylion position. Paired t tests were used to
      determine statistically significant (P < .05) changes within the variables
      between various time points (T2-T1; T3-T2; T3-T1). Correlations between variables
      were estimated by calculating Pearson's correlation coefficients. RESULTS: T2-T1
      findings: all 25 patients showed an increase in IGW with a mean of 6.5 +/- 2.5 mm
      and the angulations of the proximal segments increased 3.2 +/- 2.6 degrees (total
      angle change). Ar-B increased 3.8 +/- 3.4 mm. B point moved anteriorly 4.8 +/-
      2.9 mm. T3-T2 findings: IGW decreased 1.8 +/- 1.5 mm; angulation of the right and
      left proximal segments decreased 1.2 +/- 2.8 degrees (total angle change).
      Condylion moved superiorly 1.5 +/- 2.0. CONCLUSIONS: Statistically significant
      changes occurred in transverse width and angulation of proximal segments of
      patients who underwent BSSO advancement with Le Fort I osteotomy. No clinically
      significant associations were found between transverse displacement of the
      proximal segments and horizontal relapse.

PMID- 17174767
TI  - Thermographic assessment of inferior alveolar nerve injury in patients with
      dentofacial deformity.
AB  - PURPOSE: The purpose of this study was to evaluate the injury and recovery of the
      inferior alveolar nerve in orthognathic patients at 1 and 4 weeks after surgery
      using electronic thermography. MATERIALS AND METHODS: Twenty subjects with Class
      III dentofacial deformity were studied. All patients underwent bilateral sagittal
      split ramus osteotomy. To image the temperature of the face, 1 anteroposterior
      view and 1 lateral view were taken from both the right and left sides. Similar
      images were taken at 1 and 4 weeks after surgery. The control was the presurgical
      temperature of the 20 patients who showed unilateral or bilateral nerve damage
      after surgery. RESULTS: In the patients with unilateral nerve damage (n = 14), on
      the anteroposterior views, the temperatures of the mentum on the 2 sides differed
      by 0.64 degrees C at 1 week after surgery, and the difference decreased to 0.23
      degrees C at 4 weeks after surgery. On the lateral images, the differences in
      temperature between the mentum areas were 0.10 degrees C at 1 week and 0.27
      degrees C at 4 weeks after surgery. In the patients with bilateral nerve injury
      (n = 6), on the anteroposterior views, the temperatures of the mentum on the 2
      sides differed by 0.20 degrees C at 1 week after surgery and 0.13 degrees C after
      4 weeks. On the lateral views, the differences were 0.18 degrees C at 1 week and
      0.34 degrees C at 4 weeks after surgery. Using the repeated measurement analysis
      method, the anteroposterior view showed statistically significant results in the
      patients with unilateral nerve damage. CONCLUSION: The infrared body temperature
      method is an objective method that can be applied as a supplemental diagnostic
      method for inferior alveolar nerve injury.

PMID- 17174765
TI  - Functional sensory recovery after trigeminal nerve repair.
AB  - PURPOSE: The aim of this study was to estimate the proportion of subjects who
      achieved functional sensory recovery (FSR) 1 year after inferior alveolar or
      lingual nerve repair and to identify risk factors associated with failure to
      achieve FSR. METHODS: Using a retrospective cohort study design, we developed a
      sample composed of subjects who underwent lingual or inferior alveolar nerve
      repair. Eligible subjects had at least 1 postoperative visit. For subjects having
      bilateral nerve repair, 1 side was selected randomly for analysis. Predictor
      variables were categorized as demographic, anatomic, and operative. The outcome
      variable was the time to FSR, measured in days. Kaplan-Meier survival methods
      were used to estimate the proportion of subjects with FSR at 1 year. Uni- and
      multivariate Cox proportional hazard models were used to identify risk factors
      for the failure to reach FSR at 1 year. RESULTS: The study sample was composed of
      60 subjects with a mean age of 28.7 +/- 8.3 years; 68.3% were female. The
      majority (86.7%) of subjects presented with a preoperative chief complaint of
      altered sensation and had lingual nerve damage (93.3%) that was repaired by
      direct suturing (75%). The mean interval between injury and repair was 145.9 +/-
      200.0 days. At 1 year postoperatively, 75% of the subjects had achieved FSR (95%
      confidence interval [CI]: 64% to 86%). CONCLUSIONS: The majority of subjects
      undergoing trigeminal (V(3)) nerve repair achieved functional sensory recovery
      within 1 year of surgical repair. Patients with evidence of neuroma formation
      were less likely to achieve FSR at 1 year in a multivariate model.

PMID- 17174761
TI  - Bite force and maxillofacial morphology in patients with Duchenne-type muscular
      dystrophy.
AB  - PURPOSE: The purpose of this study is to evaluate maxillofacial morphology and
      bite force in patients with severe Duchenne-type myodystrophy. PATIENTS AND
      METHODS: The subjects included 24 men (average age, 21.5 years; range, 17 to 30
      years) with Duchenne-type muscular dystrophy receiving treatment in National Ioh
      Hospital. Lateral and axial cephalograms were used to assess the morphology in
      this study. The maximum bite force on the first molar and the maximum mouth
      opening distance were measured. RESULTS: The anterior open bite was visualized in
      most patients on the lateral cephalogram. The upper and lower arch lengths in the
      patients were significantly smaller than those in the controls (P < .05). In
      contrast, the upper and lower arch widths in the patients were significantly
      larger than those in the controls (P < .05). The maximum bite force and maximum
      mouth opening distance in the patients were significantly lower than those in the
      controls (P < .05). CONCLUSION: These results appear to be very useful for
      improving the care and treatment of patients with Duchenne-type muscular
      dystrophy.

PMID- 17174768
TI  - Ranula: experience with 83 cases in Zimbabwe.
AB  - PURPOSE: To document the clinical features, management, and outcome of ranulas in
      Zimbabwe. METHODS: A retrospective review of clinical and pathologic records of
      83 patients with ranulas who presented during the period of January 1981 to
      September 2003 was undertaken. RESULTS: Thirty-six (43.4%) of the ranulas were in
      males and 47 (56.6%) in females. Sixty-one (73.5%) were in the 0 to 10-year-old
      age group. Oral ranulas (92.8%) were equally distributed on the right and left
      sublingual region. Six (7.2%) were plunging ranulas. In a study group of 38
      patients, 88.5% of ranula patients were HIV-positive with 95% of them in the 0 to
      10-year-old age groups. Excision of ranula with sublingual gland removal was done
      in 80.7% of the cases with 0% recurrence; marsupialization (cavity left open and
      cavity packed) was done in 12% (n = 10) of the patients with 20% (n = 2)
      recurrence. CONCLUSIONS: Female predominance with no right or left sublingual
      region predilection was noted. Ranula was most common in the 0 to 10-year-old age
      group; 95% of this group were HIV positive. HIV salivary gland disease could be
      an etiologic factor. No recurrence was observed when the ranula was excised along
      with removal of the sublingual gland. Plunging ranula is uncommon.

PMID- 17174771
TI  - Delayed-onset infections after lower third molar extraction: a case-control
      study.
AB  - PURPOSE: To identify possible risk factors for delayed-onset infections and to
      develop a model for explaining the effects of these risk factors on the
      occurrence of delayed-onset infections in an outpatient clinic. MATERIALS AND
      METHODS: A retrospective case-control study comprising a total of 178 lower third
      molar extractions performed between 2001 and 2004 in the Oral Surgery and
      Orofacial Implantology Department of the School of Dentistry of the University of
      Barcelona, Spain. RESULTS: Bivariate analysis showed tooth sectioning, soft
      tissue and bone retention, and the position of the lower third molar (according
      to the classifications of Pell and Gregory, and of Winter) to be significantly
      associated with the development of delayed-onset infections. A logistic
      regression model included the following independent variables: position of the
      lower third molar according to Winter, and Pell and Gregory Classes I, II, and
      III, and degree of soft tissue retention. CONCLUSIONS: Lower third molars with
      total soft tissue retention, a lack of distal space and with a vertical or
      mesioangular tilt are more likely to develop delayed-onset infections. Tooth
      sectioning, bone retention, and depth of inclusion could also be risk factors for
      such infections. Heavy smokers seem to be more prone to this complication.

PMID- 17174770
TI  - Resorbable plates for the fixation of mandibular fractures: a prospective study.
AB  - PURPOSE: The hypothesis for this prospective evaluation is that resorbable plates
      are equal to the performance of titanium 2-mm plates, regarding healing of the
      fracture with bone union and restoration of function. To prove this hypothesis,
      specific end points will be compared with literature norms for titanium 2-mm
      miniplate rigid fixation. The primary end point variable for this analysis is the
      union of the fracture and return to normal function. Secondary end point
      variables included the incidence of complications such as infection, malunion
      with malocclusion, soft tissue dehiscence, the need for revision surgery,
      specific technical challenges, operative time, and the learning curve for the
      surgeon. PATIENTS AND METHODS: This prospective study consisted of a sequential
      enrollment of 50 fractures that met the inclusion criteria of having a fracture
      of the mandibular body, symphysis, angle, or ramus, and required an open
      reduction and internal fixation for stabilization and repair. The resorbable
      plates and screws used consisted of an amorphous injection molded copolymer of L
      lactide/D-lactide/trimethylene carbonate (Inion CPS system, Tampere, Finland).
      Data were collated and compared with literature norms for titanium plates and
      also compared with nonrigid fixation data from a prospective study performed on a
      similar population in the same institution. RESULTS: Clinical and radiographic
      evaluation indicated union of all fractures at the eighth follow-up visit. Three
      sites (6%) noted to have clinical signs of infection were treated immediately
      upon presentation, with fracture union by 8 weeks. There was no need for revision
      surgery in this series of patients; 12 screw heads fractured during screw
      placement and were immediately replaced without significant fracture sequelae.
      CONCLUSION: Based on this limited series of patients, the hypothesis formulated
      for this study was validated.

PMID- 17174769
TI  - Preoperative computed tomography imaging in the management of impacted mandibular
      third molars.
AB  - PURPOSE: The purpose of this study was to examine the role of preoperative
      computed tomography (CT) imaging of the inferior alveolar nerve (IAN) for
      patients at increased risk for nerve injury during mandibular third molar (M3)
      extraction. MATERIALS AND METHODS: To address the research purpose, the
      investigators enrolled a sample composed of subjects who presented for mandibular
      M3 extraction and had panoramic radiographic signs interpreted as being
      associated with an increased risk for inferior alveolar nerve injury. All
      subjects had preoperative CT imaging studies done to ascertain the position of
      the IAN with respect to M3. The predictor variable was the preoperative
      assessment of risk for IAN injury based on panoramic imaging. The outcome
      variable was the preoperative assessment of IAN injury risk after reviewing the
      CT studies. We documented the number of IAN injuries. Descriptive statistics were
      computed as indicated. RESULTS: The sample consisted of 23 patients who had
      bilaterally impacted wisdom teeth. The sample's mean age was 26 +/- 6 years
      (range: 18-48 years); 69.6% of the patients were female. After reviewing the
      panoramic radiographic, 80.4% of M3s were classified as having an increased risk
      for IAN injury. Upon examining the CT imaging, 32.6% were classified as high risk
      for IAN injury. After reviewing all imaging studies, 71.7% of the teeth in the
      sample were extracted. Intraoperative IAN visualization occurred in 21.2% of the
      cases. At 1 week postoperative, 3 patients had dysesthesia (9.1%); none had a
      permanent nerve injury. CONCLUSION: In this small series of patients, the
      additional information provided by 3-dimensional imaging changed the majority of
      patients from increased risk for nerve injury to low risk for nerve injury.

PMID- 17174772
TI  - Third molar periodontal pathology and caries in senior adults.
AB  - PURPOSE: This study was designed to assess the prevalence at enrollment and
      incidence over 36 months of periodontal pathology and caries affecting third
      molars in a community-based study of people over the age of 65 years in North
      Carolina. SUBJECTS AND METHODS: A sub-sample of 818 subjects with dental
      examinations taken from the Piedmont 65+ Study was available for analysis. All
      visible teeth were examined. Periodontal probing (PD) measures were taken at 2
      sites, mesiobuccal and buccal/facial. Clinical data on caries experience were
      collected by visual-tactile examination. At enrollment, 342 subjects had at least
      1 visible third molar that could be examined. PD measures were available for 276
      of these same subjects. The significance of comparisons between third molars and
      nonthird molars were determined by chi(2) tests and the statistical significance
      was set at .05. RESULTS: Most of the 342 subjects with at least 1 visible third
      molar were female (57%) or African American (63%). Mean age was 73 years (SD 5.5
      years). Of the 197 subjects with caries experience, third molars were affected in
      49% of subjects, less than the 87% in nonthird molars. Third molar caries
      experience was associated with caries experience on nonthird molar teeth (P <
      .01). Clinical attachment level (CAL) greater than 3 mm was detected at
      enrollment in third molars in 68% of subjects, and in nonthird molars in 96%.
      With one exception, CAL greater than 3 mm in third molars was associated with CAL
      greater than 3 mm elsewhere in the mouth. Few subjects (17%) had clinical
      evidence of both caries and periodontal pathology affecting third molars. In this
      older population of individuals with third molars, 21% were free of periodontal
      pathology or caries experience. CONCLUSIONS: Data on the prevalence of third
      molar periodontal pathology and third molar caries experience in an elderly
      population should be useful to both clinicians and their younger patients when
      considering the merits of retaining or removing third molars with no evidence of
      pathology.

PMID- 17174773
TI  - Intraoperative awakening of the patient during orthognathic surgery: a method to
      prevent the condylar sag.
AB  - PURPOSE: The intraoperative diagnosis, during orthognathic procedures, of an
      unfavorable condylar position is highly desirable. A simple technique that can
      reliably identify a malpositioned condyle intraoperatively has obvious
      advantages. The manual positioning of the condyle is easier, but it requires the
      utmost care and an experienced operator. Muscle tone is described as maintaining
      contact across the temporomandibular joint. The anesthetized and curarized
      patient has a condylar position posterior to that in the same patient when he is
      awake, with the same seating force applied. Under general anesthesia, the condyle
      may be inferior and might not feel stable until it moves posteriorly and has
      adequate compression of the retrodiscal tissues on the posterior wall. Relapse of
      the occlusion as a result of changes in the condylar position may occur
      immediately after the removal of the temporary intermaxillary fixation (IMF). The
      surgeon needs to understand the mechanism of condylar sag and the specific
      patterns of malocclusion that it may produce. This will enable him to make a
      diagnosis and to implement the appropriate corrective measures, providing the
      opportunity for immediate correction of condylar position, thereby obviating the
      need for a second operation or orthodontic compromise. MATERIALS AND METHODS: A
      study group (group A, 76 patients) and a control group (group B, 73 patients)
      were randomly formed from the dysgnathic patients scheduled for bimaxillary
      orthognathic surgery (Le Fort I osteotomy and bilateral sagittal split
      osteotomy). The free mandibular proximal segment was gently and manually
      positioned in the glenoid fossa. All the mandibles were fixed with bicortical
      screws. In group A, immediately after the fixation, IMFs were removed and the
      occlusions were checked with light digital pressure on the chin, then the
      patients were rapidly awakened (maintaining the intubation) in a state of
      conscious analgo-sedation and asked to open and close, and to laterally move the
      mandible. If clinical examination of the passive and active movements of the
      mandible was suitable, the anesthesia was reinforced and the operation was
      concluded. RESULTS: In 11 of the 76 patients of group A, malocclusion was noted,
      after the rigid fixation, with the method of digital pressure on the chin; the
      intraoperative awakening of the patients confirmed the clinical appearance and it
      provided further clinical signs to identify the offending condyle and to favor
      appropriate corrections. In 8 of the group A patients, malocclusions were not
      noted with manipulation of the mandible, but they were pointed out during the
      intraoperative awakening, and then they were appropriately corrected. In 2 of the
      group B patients, malocclusion was noted, after the rigid fixation, with the
      method of digital pressure on the chin, and it was immediately corrected. In 7 of
      the group B patients, malocclusion was not noted during the operation with the
      method of digital pressure on the chin, but it was noted at the end of the
      surgical procedure (12-24 hours after). CONCLUSION: Muscle tone, muscular
      activity, and proprioception appear to have important roles in the clinical
      evidence of a postoperative malocclusion during the intraoperative awakening;
      they can reliably implement the accuracy of the diagnosis of condylar sag, and
      they can favor its correction.

PMID- 17174774
TI  - Management of the ranula.

PMID- 17174775
TI  - A case against sublingual gland removal as primary treatment of ranulas.

PMID- 17174777
TI  - Giant sialolith: case report and review of the literature.

PMID- 17174776
TI  - The perioperative management of metformin for the oral and maxillofacial surgery
      patient: risks and recommendations.

PMID- 17174778
TI  - Mandibular asymmetry after lesion of the trigeminal motor nucleus: a case report.

PMID- 17174780
TI  - Sialectasis of Stensen's duct with an extraoral swelling: a case report with
      surgical management.

PMID- 17174779
TI  - Kimura's disease of the parotid region: report of 2 cases and review of the
      literature.

PMID- 17174781
TI  - Osteomyelitis of the maxilla secondary to osteopetrosis: a report of 2 cases in
      sisters.

PMID- 17174782
TI  - Undifferentiated cardiac sarcoma metastatic to the maxilla: report of a case.

PMID- 17174784
TI  - The medical degree: impact on the clinical scope of practice.

PMID- 17174783
TI  - A modified approach toward management of complete cleft of lip and palate in
      slightly older children-the complete palate repair first.

PMID- 17174785
TI  - Tooth extraction: Is it inciting event or sequela of osteonecrosis of the jaws
      associated with intravenous bisphosphonates?

PMID- 17174786
TI  - Work hour regulations and training of residents.

PMID- 17174787
TI  - Introspection in science.

PMID- 17174788
TI  - 'Introspectionism' and the mythical origins of scientific psychology.
AB  - According to the majority of the textbooks, the history of modern, scientific
      psychology can be tidily encapsulated in the following three stages. Scientific
      psychology began with a commitment to the study of mind, but based on the method
      of introspection. Watson rejected introspectionism as both unreliable and effete,
      and redefined psychology, instead, as the science of behaviour. The cognitive
      revolution, in turn, replaced the mind as the subject of study, and rejected both
      behaviourism and a reliance on introspection. This paper argues that all three
      stages of this history are largely mythical. Introspectionism was never a
      dominant movement within modern psychology, and the method of introspection never
      went away. Furthermore, this version of psychology's history obscures some deep
      conceptual problems, not least surrounding the modern conception of "behaviour,"
      that continues to make the scientific study of consciousness seem so weird.

PMID- 17174790
TI  - Reversible ischemia in Wellens' syndrome.

PMID- 17174789
TI  - Positron emission tomography myocardial perfusion and glucose metabolism imaging.

PMID- 17174791
TI  - American Society of Nuclear Cardiology consensus statement: Reporting of
      radionuclide myocardial perfusion imaging studies.

PMID- 17174793
TI  - American Society of Nuclear Cardiology information statement: Standardized
      reporting matrix for radionuclide myocardial perfusion imaging.

PMID- 17174794
TI  - Abnormal focal pulmonary tracer uptake on myocardial perfusion imaging studies.

PMID- 17174795
TI  - Instrumentation quality assurance and performance.

PMID- 17174796
TI  - First-pass radionuclide angiography.

PMID- 17174797
TI  - Equilibrium radionuclide angiocardiography.

PMID- 17174798
TI  - Stress protocols and tracers.

PMID- 17174799
TI  - Myocardial perfusion planar imaging.

PMID- 17174801
TI  - Two alarming recent statistics: the increase in the uninsured and the increased
      prediction of the number of persons living with diabetes.

PMID- 17174802
TI  - Fluorodeoxyglucose and calcium uptake in the vascular wall: clinically relevant
      or sugar-coated pill?

PMID- 17174804
TI  - The Achilles heel of SPECT imaging: the false-positive scans--or are they?

PMID- 17174800
TI  - Myocardial perfusion and function single photon emission computed tomography.

PMID- 17174803
TI  - Revascularize only for ischemia, especially if left ventricular function is poor.

PMID- 17174805
TI  - Cardiac imaging in the evaluation of patients presenting to the emergency
      department with chest pain.

PMID- 17174806
TI  - Vascular endothelial dysfunction is associated with reversible myocardial
      perfusion defects in the absence of obstructive coronary artery disease.
AB  - BACKGROUND: The purpose of this study was to investigate whether endothelial
      dysfunction contributes to abnormal myocardial perfusion imaging (MPI) observed
      in patients without obstructive coronary artery disease (CAD). It is unclear
      whether reversible MPI defects detected in the absence of obstructive CAD
      represent underlying vascular pathology or are false-positive MPI results. Recent
      evidence suggests that coronary endothelial dysfunction might play a role in the
      pathogenesis of these defects. METHODS AND RESULTS: We prospectively recruited 36
      patients with chest discomfort, reversible abnormalities on MPI, and
      nonobstructive or absent CAD (stenosis <50% on coronary angiography). The control
      group (n = 55) consisted of patients with chest discomfort and similar cardiac
      risk factors but with normal MPI findings. Vascular endothelial function was
      assessed in the brachial artery by ultrasound as the response to hyperemia and
      reported as percent flow-mediated dilation (FMD). Response to sublingual
      nitroglycerin was used as an indicator of endothelium-independent vasodilation.
      The patients with abnormal MPI findings and nonobstructive CAD had a
      significantly lower FMD (9.0% +/- 7.2%), indicating endothelial dysfunction,
      compared with those with similar risk factors and normal MPI findings (12% +/-
      5.2%) (P = .03). Baseline brachial artery size and endothelium-independent
      dilation were similar between groups. On multivariate analysis, only endothelial
      dysfunction was predictive of reversible MPI defects. CONCLUSIONS: Patients with
      chest pain and reversible MPI defects but without obstructive CAD have lower FMD
      indicative of endothelial dysfunction, as compared with similar patients with
      normal MPI findings. The possibility of a causal link between reversible MPI
      defects and endothelial dysfunction needs further exploration.

PMID- 17174807
TI  - Coronary vasodilator reserve and Framingham risk scores in subjects at risk for
      coronary artery disease.
AB  - BACKGROUND: The relationship between coronary vasodilator reserve and risk of
      coronary heart disease (CHD) in subjects without coronary artery disease (CAD) is
      not well known. METHODS AND RESULTS: We studied 289 subjects (mean age, 58 +/- 10
      years) without overt CAD and at low (< 10%) to intermediate risk (10%-20%) for
      CHD based on Framingham risk scores (RAMPART [Relative and Absolute Myocardial
      Perfusion changes as measured by Positron Emission Tomography to Assess the
      Effects of ACAT Inhibition: A Double-Blind, Randomized, Controlled, Multicenter
      Trial]). Coronary flow reserve (CFR) and coronary vascular resistance (CVR) were
      calculated from rest and adenosine nitrogen 13 ammonia positron emission
      tomography studies. Framingham-estimated CHD risk was used to as a surrogate for
      outcomes. Compared with subjects with low-risk scores (n = 150), those with
      intermediate-risk scores (n = 139) had a higher minimal CVR (49.3 +/- 17.41 mm Hg
      x mL(-1) x min(-1) x g(-1) vs 52.4 +/- 16.4 mm Hg x mL(-1) x min(-1) x g(-1), P =
      .05) and lower CFR (2.8 +/- 1.0 vs 2.5 +/- 0.8, P = .02). CFR was inversely
      related to CHD risk (R = -0.2, P = .006), and CVR was directly related to CHD
      risk (R = 0.2, P < .001). The mean CFR was significantly lower in patients in the
      first quartile of CHD risk compared with those in the fourth quartile (2.3 +/-
      0.7 vs 2.8 +/- 1.0, P = .02), and the minimal CVR was significantly higher (44 +/
      15 mm Hg x mL(-1) x min(-1) x g(-1) vs 53 +/- 14 mm Hg x mL(-1) x min(-1) x g(
      1), P < or = .05). CONCLUSIONS: In subjects without clinical CAD and at low to
      intermediate risk, CFR assessed by positron emission tomography is inversely
      related to estimated 10-year CHD risk.

PMID- 17174809
TI  - Organ biodistribution and myocardial uptake, washout, and redistribution kinetics
      of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of
      coronary stenoses.
AB  - BACKGROUND: Technetium 99m N-DBODC5 is a new myocardial perfusion tracer shown to
      exhibit high heart uptake and rapid liver clearance in normal rats. The
      objectives of this canine study were (1) to compare the organ biodistribution and
      myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 with
      Tc-99m sestamibi over a period of 3 hours in a more clinically relevant large
      animal species and (2) to compare the myocardial uptake of Tc-99m N-DBODC5 with
      thallium 201 when co-injected during vasodilator stress in dogs with coronary
      stenoses. METHODS AND RESULTS: At peak adenosine-induced hyperemia, 10 dogs with
      critical left anterior descending artery stenoses received either Tc-99m N-DBODC5
      (n = 6) or Tc-99m sestamibi (n = 4) and microspheres, followed by serial imaging
      and blood sampling over a period of 3 hours. Another 14 dogs with either critical
      (n = 7) or mild (n = 7) left anterior descending artery stenoses underwent
      simultaneous injection of Tc-99m N-DBODC5, Tl-201, and microspheres during peak
      vasodilator stress. Like sestamibi, Tc-99m N-DBODC5 showed good myocardial uptake
      with slow washout and minimal redistribution over a period of 3 hours (P = not
      significant); however, Tc-99m N-DBODC5 cleared more rapidly from the liver (heart
      lung ratio at 30 minutes, 0.92+/-0.11 versus 0.51 +/- 0.05; P < .05). When
      injected during hyperemic flow, the myocardial extraction plateau for Tc-99m N
      DBODC5 was lower than that for Tl-201 and was intermediate between Tc-99m
      sestamibi and Tc-99m tetrofosmin. CONCLUSIONS: Excellent organ biodistribution
      and myocardial uptake and clearance kinetic properties, combined with rapid liver
      clearance and a favorable flow-extraction relationship, make Tc-99m N-DBODC5 a
      very promising new myocardial perfusion imaging agent.

PMID- 17174808
TI  - Predicting therapeutic benefit from myocardial revascularization procedures: are
      measurements of both resting left ventricular ejection fraction and stress
      induced myocardial ischemia necessary?
AB  - BACKGROUND: We hypothesized that ejection fraction (EF) best predicts
      cardiovascular death but only measures of ischemia predict relative survival
      benefit from revascularization compared with medical therapy. METHODS AND
      RESULTS: We followed up 5366 consecutive patients without prior revascularization
      who underwent stress electrocardiography-gated myocardial perfusion single photon
      emission computed tomography (MPS) for 2.8 +/- 1.2 years, during which 146
      cardiac deaths occurred (2.7%, 1.0%/y). The treatment received within 60 days
      after MPS was used to define the subgroups (revascularization in 402 patients,
      with cardiac death occurring in 6.2%, vs medical therapy in 4964 patients, with
      cardiac death occurring in 2.4%; P < .0001, chi2 = 18.7). Adjustment for
      nonrandomized treatment assignment used a propensity score based on logistic
      regression modeling of referral to revascularization. The percent of myocardium
      that was ischemic was the most important predictor of revascularization. The
      overall model (multivariate chi2 = 728, c index = 0.89, P < 10(-5)) was used as a
      propensity score. Cox proportional hazards analysis, assessing the relationship
      between MPS results, non-MPS covariates, and cardiac death, revealed that EF was
      superior to percent ischemic myocardium in the prediction of cardiac death after
      adjustment for pre-MPS data and the propensity score. However, an interaction
      between percent ischemic myocardium and revascularization was present such that,
      irrespective of EF, patients with little or no ischemia had an improved survival
      rate with medical therapy, whereas with increasing ischemia, progressive
      improvements in survival rate were noted with revascularization. CONCLUSIONS:
      Although EF predicts cardiac death, only inducible ischemia identifies which
      patients have a short-term benefit from revascularization.

PMID- 17174811
TI  - Multicenter intercomparison assessment of consistency of left ventricular
      function from a gated cardiac SPECT phantom.
AB  - BACKGROUND: A multicenter intercomparison assessment was made of the variation in
      left ventricular (LV) volumes and ejection fractions (EFs) obtained from gated
      myocardial perfusion single photon emission computed tomography (SPECT) of the 3
      dimensional AGATE (Amsterdam gated) cardiac phantom. METHODS AND RESULTS: The
      phantom was configured to produce 3 different standard end-systolic volume and
      end-diastolic volume combinations (50 mL and 120 mL, 90 mL and 160 mL, and 120 mL
      and 190 mL) with corresponding EF (58%, 44%, and 37%). Quantitative gated
      myocardial perfusion SPECT was performed with 39 SPECT systems in 35 departments.
      In the multicenter study, for all 3 filling conditions, a wide range of results
      was obtained. The EF was overestimated (by 1% to 15%), and both the end-systolic
      volume and end-diastolic volume were underestimated (by 1 to 65 mL). The extent
      of overestimation of EF was related to the extent of underestimation of the
      volumes and was independent of filling condition. The trend in error per center
      was comparable for all 3 filling conditions. Acquisition time per projection was
      the only independent predictor of the difference between measured and expected EF
      (P = .0001). CONCLUSIONS: Care should be taken before extrapolation of published
      and accepted cutoff values for LV EF and volumes in clinical decision making.
      Results should be validated in each center and monitored for accuracy and
      consistency over time.

PMID- 17174810
TI  - Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on
      follow-up PET/CT studies.
AB  - BACKGROUND: Fluorine 18 fluorodeoxyglucose (FDG) uptake may be increased in
      atherosclerotic plaques in asymptomatic patients. Repeat positron emission
      tomography (PET)/computed tomography (CT) studies were assessed for changes in
      patterns of FDG uptake and CT calcifications. METHODS AND RESULTS: Fifty
      consecutive cancer patients (mean age, 68 +/- 8 years) had repeat PET/CT studies
      8 to 26 months apart. PET, CT, and PET/CT images were retrospectively evaluated
      for vascular wall abnormalities and for interval changes in the thoracic and
      abdominal aortas, as well as in carotid and iliac arteries, classified as
      PET+/CT+, PET+/CT-, and PET-/CT+. There were 485 abnormal sites in the first
      study and 495 in the second. CT calcifications were found in 46 patients (92%) in
      the first study and in 47 (94%) in the second. Vascular wall FDG uptake was found
      in both studies in 37 patients (74%). The pattern changed in 57 of 119 PET+ sites
      (48%) in the second study compared with 15 of 366 PET- sites (4%) (P < .0001). In
      the second study new PET+ sites were observed in 36 of 111 sites (32%) versus new
      PET-/CT+ sites in 19 of 384 sites (5%) (P < .0001). CONCLUSIONS: Changes in
      vascular FDG activity and CT calcifications can be assessed by repeat PET/CT. FDG
      avid foci may represent a dynamic process, transient inflammation, whereas CT
      calcifications may indicate stable atherosclerosis. These preliminary results
      support the need for further research.

PMID- 17174812
TI  - Gated blood pool tomoscintigraphy with 4-dimensional optical flow motion analysis
      quantifies left ventricular mechanical activation and synchronization.
AB  - BACKGROUND: Gated blood pool tomoscintigraphy has the unique capacity to
      accurately assess myocardial motion in paced patients. Our goal was to develop a
      precise radionuclide angiography analysis of cardiac dynamics to evaluate
      ventricular synchronization in patients undergoing biventricular pacing. METHODS
      AND RESULTS: On the basis of a 4-dimensional deformable motion estimation
      algorithm, we developed a protocol allowing estimation of motion fields after
      gated blood pool tomoscintigraphy. We measured the mechanical activation times
      for 17 left ventricular (LV) segments and determined the main types of
      contraction pattern in 10 normal subjects, 17 patients with dilated
      cardiomyopathy, and 12 resynchronized patients. We analyzed intra-LV
      dyssynchrony: apex to base, septum to lateral wall, and anterior wall to inferior
      wall. Three-dimensional measurements of intra-LV activation time (r > .80, P <
      .001) and LV ejection fraction (r > 0.90, P < .0001) are linearly correlated to 2
      dimensional values. LV contraction follows the electrical activation pattern. In
      normal subjects the anteroseptal and anterior segments are first activated,
      followed by the apex and inferolateral segments. In resynchronized patients
      contraction begins with the lateral and apicoseptal segments in correspondence to
      the LV and right ventricular lead implantation. CONCLUSIONS: By measuring
      mechanical activation times, this technique allows for the analysis of the
      regional synchronous contraction. This may help to assess the variation of the
      activation pattern according to the cardiomyopathy type and the role of septal
      resynchronization in ventricular functional recovery.

PMID- 17174813
TI  - PET/CT imaging: effect of respiratory motion on apparent myocardial uptake.
AB  - BACKGROUND: Positron emission tomography (PET) attenuation correction (AC) using
      computed tomography (CT) can be affected by respiratory motion: hi-speed CT
      captures 1 point of the respiratory cycle while PET emission data averages many
      cycles. We quantified the changes in apparent myocardial uptake due to this
      respiratory-induced CT attenuation mismatch. METHODS: Twenty-two patients
      undergoing fluorine-18 fluorodeoxyglucose (FDG) PET/CT received 3 sequential CT
      scans at normal resting end-inspiration (CT(INSPIR)), ending expiration
      (CT(EXPIR)), and at midvolume between end-expiration and end-inspiration
      (CT(MIDVOL)). A pneumotachometer measured absolute changes in lung volume. Seven
      subjects also underwent a 3-minute transmission scan with a 68Ge rotating rod
      source (RRS). The PET emission data set was reconstructed up to 4 times using
      CT(EXPIR), CT(INSPIR), CT(MIDVOL), and RRS AC maps. Relative heart position and
      cardiac uptake was measured for each CT attenuation correction. RESULTS:
      Respiratory motion produced marked changes in global and regional myocardial
      uptake. Changes were large in the lateral and anterior regions at the lung-soft
      tissue interface (up to 30% using CT(INSPIR) compared to CT(EXPIR) for AC) and
      smaller in the septal region (10% or less). Data corrected with CT(EXPIR) agreed
      best with the RRS. CONCLUSION: Respiratory effects can introduce large
      inhomogeneities in apparent myocardial uptake when CT is used for attenuation
      correction.

PMID- 17174814
TI  - Imaging of atherosclerotic plaque using radiofrequency ultrasound signal
      processing.

PMID- 17174815
TI  - Myocardial perfusion imaging by cardiac magnetic resonance.
AB  - Cardiovascular magnetic resonance (CMR) has been shown to provide high quality
      data on cardiac and valvular function, perfusion, viability, blood flow, and
      potentially, on cardiac metabolism as well. Several of these CMR applications
      (eg, function and viability assessment) matured during the past years and are now
      established components of a cardiac workup. Perfusion-CMR is close to this status
      and is already a major contributor to cardiac examinations in a growing number of
      expert centers. Large multicenter perfusion-CMR trials comparing the diagnostic
      performance of CMR with other techniques were recently reported yielding areas
      under the receiver-operator-characteristics curve as a high as 0.85 for coronary
      artery disease detection (MR-IMPACT). Anticipating a growing role for perfusion
      CMR in cardiology in the near future, this article discusses the principles of
      perfusion-CMR and its integration into the workup of patient with coronary artery
      disease (CAD). In addition to a functional study, this integration is mainly
      composed of a perfusion-CMR part, followed by a viability assessment by late
      enhancement CMR techniques. The principal characteristics of these CMR techniques
      are compared with those of single photon emission computed tomography (SPECT) and
      positron emission tomography (PET). After introduction into principles and
      techniques of perfusion-CMR, some open questions in perfusion-CMR and challenges
      for the future are addressed. Finally, newer CMR applications are shortly
      mentioned utilizing hyperpolarized carbon-13 compounds in experimental models for
      quantification of myocardial perfusion and for real-time assessment of metabolic
      pathways in postischemic myocardium.

PMID- 17174816
TI  - Optimal SPECT processing and display: making bad studies look good to get the
      right answer.

PMID- 17174817
TI  - Dramatic change of Ga-67 citrate uptake before and after corticosteroid therapy
      in a case of cardiac histiocytosis (Erdheim-Chester disease).

PMID- 17174818
TI  - Radionuclide imaging in Takayasu's arteritis: two case presentations.

PMID- 17174819
TI  - Inflammatory F-18 fluorodeoxyglucose uptake over arterial bypass prosthesis seen
      on positron emission tomography can predict acute vascular events.

PMID- 17174820
TI  - Gender-specific normal values for transient ischemic dilation.

PMID- 17174824
TI  - Dysmenorrhea in adolescents and young adults: etiology and management.
AB  - Dysmenorrhea is the most common gynecologic complaint among adolescent and young
      adult females. Dysmenorrhea in adolescents and young adults is usually primary
      (functional), and is associated with normal ovulatory cycles and with no pelvic
      pathology. In approximately 10% of adolescents and young adults with severe
      dysmenorrhea symptoms, pelvic abnormalities such as endometriosis or uterine
      anomalies may be found. Potent prostaglandins and potent leukotrienes play an
      important role in generating dysmenorrhea symptoms. Nonsteroidal anti
      inflammatory drugs (NSAID) are the most common pharmacologic treatment for
      dysmenorrhea. Adolescents and young adults with symptoms that do not respond to
      treatment with NSAIDs for 3 menstrual periods should be offered combined
      estrogen/progestin oral contraceptive pills for 3 menstrual cycles. Adolescents
      and young adults with dysmenorrhea who do not respond to this treatment should be
      evaluated for secondary causes of dysmenorrhea. The care provider's role is to
      explain about pathophysiology of dysmenorrhea to every adolescent and young adult
      female, address any concern that the patient has about her menstrual period, and
      review effective treatment options for dysmenorrhea with the patient.

PMID- 17174822
TI  - Collimator integrity.

PMID- 17174826
TI  - Estrogen treatment success in recurrent and persistent labial agglutination.
AB  - STUDY OBJECTIVE: To estimate the success rate of conservative medical management
      and indications for surgery in cases of recurrent and/or persistent labial
      agglutination. DESIGN: A retrospective chart review was performed of girls
      treated for labial agglutination between 1996 and 2004. Records were reviewed for
      age, length of time of symptoms, previous treatments, results of topical estrogen
      therapy, and indications for surgery. SETTING: The study was performed in a
      tertiary care teaching university hospital. PARTICIPANTS: Charts of 67 girls with
      labial agglutination who were treated at the pediatric and adolescent gynecology
      clinic between 1996 and 2004 were reviewed. The average age was 4.1 years (range
      0.6-14 years). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Improvement of
      persistent or recurrent agglutination labial agglutination with estrogen.
      RESULTS: Out of the 67 charts reviewed, 48 had recurrent or persistent disease.
      Within those 48 girls, initial treatments included: topical estrogen in 40 (83%),
      oral and topical estrogen in 1 (2%), topical estrogen in addition to manual
      separation in 5 (10%), and treated with manual separation alone in 2 (4%). Five
      girls were immediately treated surgically due to urinary problems or parents
      declining further topical treatment. Forty-three were treated with topical
      estrogen therapy with the following results: 15 opened either partially or
      completely, 9 required surgery, and 19 did not follow up. In the subset of girls
      with prior manual separation, 2 had resolution of adhesions with estrogen, 3
      required surgery, and 2 had no follow-up. CONCLUSION: This study suggests that re
      treatment of persistent or recurrent labial agglutination with topical estrogen
      therapy following detailed application instruction leads to avoidance of surgical
      intervention in at least 35% of cases. Even in cases which previously required
      manual separation, an attempt at conservative medical management may be
      considered.

PMID- 17174825
TI  - Adolescent girls' communication with "mothers" about topical microbicides.
AB  - STUDY OBJECTIVE: Topical microbicides, a female-initiated method to protect
      against sexually transmitted infections (STI) and pregnancy, will only be
      effective if found acceptable. Mothers may have an influence on acceptability and
      use among adolescent girls. The current study examined the communication between
      girls and mothers to understand the potential predictors and nature of
      conversations regarding surrogate microbicide products. DESIGN: Sexually
      experienced girls, 14 to 21 years, were recruited for a 6-month study examining
      microbicide acceptability. During face-to-face interviews, qualitative data were
      collected regarding communication between girls and mothers. Two independent
      raters coded the responses, which were organized into themes. Themes were
      interpreted according to the conceptual understanding of mother-daughter
      communication. RESULTS: Fifty percent of the 171 girls with codable responses had
      a conversation with their mother. Higher levels of indirect parental monitoring
      were related to being more likely to have a conversation. Concrete events related
      to the study (i.e. receiving phone call from the researcher, having an
      appointment, or seeing the product) or inquiries by mothers appeared to promote
      conversation. Barriers to conversation included the private nature of the
      information and relationship issues between the mother and daughter.
      Conversations often addressed issues related to girls' participation in the
      study, although some conversations included global issues related to sexuality.
      CONCLUSIONS: Girls may talk to their mothers about new products for STI
      prevention, and such conversations may provide opportunities to promote use.

PMID- 17174827
TI  - Maternal age and the size of White, Black, Hispanic, and mixed infants.
AB  - OBJECTIVE: To clarify the interaction between maternal age and race in the
      prediction of infant size at birth. METHODS: Birth certificate data was used to
      study the relationship between maternal age, race/ethnicity, and the size of
      term, singleton infants born to 91,061 healthy, non-smoking, non-substance using,
      primigravidas. RESULTS: Maternal race/ethnicity (Black race: OR: 1.95, 95% CI:
      1.49-2.56; Hispanic ethnicity: OR: 1.38, 95% CI: 1.19-1.61) and the interaction
      term, maternal age x race/ethnicity (OR: 1.06, 95% CI: 1.01-1.11) predicted small
      for-gestational age (SGA) birth. The strength of the association between Black
      race and SGA delivery increased and the strength of the association between
      Hispanic ethnicity and SGA delivery decreased with age (P < 0.001 for trend).
      Thus, Black and Hispanic teenagers were more likely to have SGA babies than White
      teenagers (1.7% and 1.6%, respectively compared to 1.2%; P = 0.003). However,
      Black women who postponed childbearing until their mid-twenties were more likely
      to have SGA babies than their Hispanic and White counterparts (2.6% compared to
      1.2%, and 1.0%, respectively; P < 0.0001). CONCLUSION: The findings suggest that
      acquired maternal characteristic(s) cause the reproductive health of Black
      primigravidas to deteriorate and Hispanic primigravidas to improve with age.

PMID- 17174828
TI  - Turkish adolescents' knowledge on and attitude toward emergency contraception.
AB  - OBJECTIVE: Adolescents tend to be at risk for unwanted pregnancies, so detecting
      their level of knowledge on emergency contraception and providing them
      information is important to prevent such pregnancies. Hence, in two faculties at
      Gazi University, this study aimed to detect freshman students' level and need of
      knowledge on emergency contraception and to evaluate their attitude towards
      emergency contraception. MATERIALS AND METHODS: The study was performed with
      freshman students of the Occupational Education Faculty and the Technical
      Education Faculty. A questionnaire including questions about demographic
      properties, obstetrical history, status of contraceptive use, level of knowledge
      and opinions on emergency contraception was administered to the students. Data
      was analyzed statistically with the computer program EPI Info 6.0. RESULTS: A
      total number of 385 adolescents were included in the studys; 157 of whom were
      males (40.8%) and 228 of whom were females (59.2%). To the question "is there any
      way to prevent a possible pregnancy after an unprotected sexual intercourse?",
      166 students replied "yes" (50.5%), 39 "no" (11.9%) and 124 "I do not know"
      (37.7%). Of 166 students replying "yes," 114 (68.7%) listed a possible
      contraceptive method. The mostly cited method was "morning after pills" (n = 62;
      54.4%), followed by curettage (n = 15; 13.2%). Among all students, 158 (49.8%)
      informed us that they were aware of the presence of "morning after pills" whereas
      159 (50.2%) claimed they were not. Eighty-six male students (70.5%) and 115
      female students (72%) emphasized that they would use emergency contraception upon
      necessity. CONCLUSION: Half of the participants were familiar with various
      options to prevent pregnancy after an unprotected sexual intercourse episode, but
      they lacked specific knowledge about possible methods and ways to use them. Thus,
      it is essential that information about emergency contraception be included in
      adolescents' educational programs and that adolescents be provided with easily
      accessible medical services.

PMID- 17174829
TI  - Premenstrual syndrome (PMS) in adolescents: severity and impairment.
AB  - OBJECTIVES: Identify the presence of patients with premenstrual syndrome (PMS) in
      an adolescent gynecology practice, and evaluate the reported severity, impairment
      and timing of the symptoms in the menstrual cycle. METHODS: Adolescents ages 13
      18 years completed a symptom questionnaire, functional impairment ratings, and a
      brief medical history questionnaire during an office visit. Teens who responded
      that they had PMS and reported a premenstrual symptom score at least 50% greater
      than the postmenstrual score and rated moderate to severe impairment in one or
      more domains comprised the "PMS" group. Teens who responded that they had PMS but
      did not meet the symptom and impairment criteria were termed "PMS not supported."
      Teens who responded that they did not have PMS and did not meet the PMS symptom
      and impairment criteria were termed "No PMS." RESULTS: Study participants (n =
      94) had a mean age of 16.5 years (+/-1.3 SD); 31% met the criteria for the PMS
      group, 54% said they had PMS but did not meet criteria, and 15% clearly had no
      PMS. In the PMS group, the most severe symptoms were mood swings, anxiety, and
      irritability, with the greatest impairment in the home/family domain.
      Dysmenorrhea and the duration of PMS were significantly associated (P < 0.01)
      with PMS in univariate and multivariate analyses. CONCLUSIONS: The reports of
      premenstrual symptoms, their severity, timing and impairment suggest that PMS is
      common in adolescents. Further study is warranted to confirm these results with
      prospective assessment of PMS and to evaluate treatments for adolescents who have
      clinically significant PMS.

PMID- 17174830
TI  - Laparoscopic management of mature cystic teratoma of bilateral ovaries with
      adnexal torsion occurring in a 9-year-old premenarchal girl.
AB  - BACKGROUND: Laparoscopic surgery is a minimal-access procedure with many
      advantages. However, reports of young girls with adnexal disease treated by
      laparoscopic surgery are limited in the literature. CASE: A 9-yr-old premenarchal
      girl presenting with acute abdomen was treated by emergency laparoscopic surgery.
      Bilateral adnexal torsion was noted. After detorsion, bilateral cystectomy was
      successfully performed and ovarian tissues were preserved. Pathological diagnosis
      was mature cystic teratoma of bilateral ovaries. CONCLUSION: Although adnexal
      torsion occurring in a premenarchal girl is an extremely rare disorder and
      bilateral adnexal torsion is even more rare, gynecologists should possess
      sufficient knowledge about the manifestations of such disorder for immediate
      diagnosis and treatment to preserve future fertility and, if available,
      laparoscopic approach should be chosen for a young girl.

PMID- 17174831
TI  - Betamethasone cream for the treatment of pre-pubertal labial adhesions.
AB  - PURPOSE: We evaluated the efficacy of 0.05% betamethasone cream for the treatment
      of pre-pubertal labial adhesions. METHODS: We retrospectively reviewed the
      records of 19 children with labial adhesions who were treated with betamethasone
      cream from 6/2001 to 3/2003. Children were treated with 1 to 3 courses of twice
      daily 0.05% betamethasone cream for 4 to 6 weeks. Successful lysis of adhesions
      was assessed by clinical exam or parental phone contact and outcomes were defined
      as: (1) success--complete separation of labia, (2) partial success--greater than
      75% separation, (3) progression to surgical lysis, and (4) lost to follow-up.
      RESULTS: Nineteen patients with an average age of 58 months (range 12 to 132
      months) were treated. Four of the 19 patients had never been treated previously
      and 1 had been treated previously with surgical lysis of adhesions only. Fourteen
      of the 19 patients had been previously treated with conjugated estrogen
      (Premarin) cream. Two of these fourteen patients had also undergone surgical
      lysis of adhesions. Severity of adhesions ranged from 33% to 99% labial closure.
      Betamethasone cream was successful in treating 13/19 (68%) pre-pubertal labial
      adhesions. Eleven (85%) of these 13 patients had complete resolution of labial
      adhesions with 1 course of treatment, 1 (7.5%) had resolution with 2 courses of
      treatment and 1 (7.5%) had resolution with 3 courses of treatment. One patient
      had a partial success with 3 courses of betamethasone cream. Two (11%) patients
      underwent surgical lysis of adhesion after 1 and 2 courses of betamethasone cream
      respectively. Three (16%) patients were lost to follow-up. Average follow-up was
      7 months (range 1-24 months). No adverse outcomes or untoward effects were noted
      in any of the patients treated. CONCLUSIONS: Betamethasone 0.05% cream appears to
      be a safe and effective treatment of pre-pubertal labial adhesions as primary
      therapy or in patients that have failed previous therapies and it may avoid the
      undesirable side effects of breast budding and hyperpigmentation that can be
      associated with Estrogen creams.

PMID- 17174832
TI  - Mothers and daughters: the challenge of communicating.

PMID- 17174833
TI  - Disorders of the breast in children and adolescents, Part 2: breast masses.

PMID- 17174835
TI  - Cervical cancer vaccine.

PMID- 17174834
TI  - Management Quandary. Management of an adolescent mother and breastfeeding.

PMID- 17174837
TI  - Update on syndromes with cutaneous manifestations and new diagnoses in
      dermatology.
AB  - Systemic syndromes with cutaneous manifestations represent a continually evolving
      entity. New syndromes are described, while improved understanding of others, with
      new features of disease or enhanced genetic understanding of the disease are
      discovered. This review highlights the latest information on syndromes with
      cutaneous manifestations and presents several newly described dermatologic
      diagnoses.

PMID- 17174838
TI  - Emerging dermatologic issues in the oncology patient.
AB  - The spectrum of skin diseases that occurs in the oncology patient differs
      somewhat from that seen in other immunosuppressed populations. We review the
      cutaneous manifestations of invasive mold infections in the leukemia/lymphoma
      population. Aspergillus mold infections are now the leading infectious cause of
      death in this population. We also review the pustular eruption caused by a new
      class of chemotherapy for solid malignancies. An update on cutaneous graft-versus
      host disease appears elsewhere in this journal. Cutaneous squamous cell
      carcinomas and basal cell carcinomas occur more frequently in the chronic
      lymphocytic leukemia and non-Hodgkin's lymphoma population; this is discussed, as
      is the more aggressive clinical course of these tumors.

PMID- 17174839
TI  - The changing face of graft-versus-host disease.
AB  - Despite advances in the procedure and posttransplantation immunosuppressive
      therapy, more than half of allogeneic hematopoietic stem cell transplant (HSCT)
      recipients develop graft-versus-host disease (GVHD), which remains a major cause
      of morbidity and mortality. Modern HSCT protocols have resulted in substantial
      alterations in the timing and relative incidences of acute and chronic GVHD,
      making traditional classification schemes obsolete. This article reviews major
      changes in HSCT during the past decade, evolving concepts of acute and chronic
      GVHD (including new diagnostic criteria) and the expanding spectrum of cutaneous
      GVHD. It focuses on observations that have led to a better delineation of the
      full constellation of skin findings in chronic cutaneous GVHD, including lichen
      sclerosus, morpheaform lesions, and eosinophilic fasciitis. Recent insights into
      pathogenesis of GVHD, lessons from GVHD arising in settings outside HSCT, and
      therapeutic advances also are highlighted.

PMID- 17174840
TI  - Emerging infections in dermatology.
AB  - Cutaneous infections are common in dermatology. They occur in all populations and
      all ages. This review will focus on 3 emerging infections encountered by
      dermatologists; community-acquired methicillin-resistant Staphylococcus aureus,
      Epstein-Barr virus infections, and the atypical mycobacterial infections. The
      background, clinical presentation, diagnosis, and treatment of each of the 3
      infections will be discussed.

PMID- 17174841
TI  - Update on connective tissue diseases in dermatology.
AB  - Recent advances in understanding the pathogenesis of autoimmune diseases,
      including lupus erythematosus, dermatomyositis, and scleroderma, have allowed for
      reorganization of the classification of these disorders. With these novel
      stratifications, early identification of rheumatic skin diseases with systemic
      implications and consistency in designing and executing therapeutic trials will
      be enhanced. This review will provide a compilation of updates on epidemiology,
      pathology, evaluation, and classification with a predominant focus on
      therapeutics, reflecting the growth is this area.

PMID- 17174842
TI  - Update on cutaneous vasculitis.
AB  - Vasculitis presents with a range of clinical manifestations, many of which affect
      the skin. Diagnosing and classifying vasculitis can prove challenging.
      Particularly given the lack of unified criteria that are both useful as a
      research tool and clinically relevant. Also, vasculitis may be secondary to a
      wide range of conditions, making the prompt recognition and treatment of
      associated disorders essential for appropriate patient management. This article
      will highlight the classification, pathogenesis, clinical presentation,
      diagnosis, evaluation, and treatment of the cutaneous vasculitides.

PMID- 17174843
TI  - Off-label uses of biologic agents in dermatology: a 2006 update.
AB  - The introduction of a number of biologic therapies into the market has
      revolutionized the practice of dermatology. These therapies include adalimumab,
      alefacept, efalizumab, etanercept, infliximab, IVIg, omalizumab, and rituximab.
      Most dermatologists are familiar with the indications of these medications that
      have been approved by the Food and Drug Administration; however, numerous off
      label uses have evolved. To update the reader on more recent uses of the
      biologics for off-label dermatologic use, this article will emphasize more recent
      published data from 2005 through the date of submission in May 2006.

PMID- 17174845
TI  - Psychosocial risk factors for eating disorders in Hispanic females of diverse
      ethnic background and non-Hispanic females.
AB  - This study investigated differences in psychosocial risk factors for eating
      disorders among university females (n=406) of diverse Hispanic background (Puerto
      Rican, Cuban, Central American/Mexican, Dominican, Venezuelan) and among White
      non-Hispanic (n=102) female students. Risk factors were assessed using the
      Psychosocial Risk Factor Questionnaire (PRFQ) which includes four subscales:
      Social Pressure for Thinness, Media Pressure for Thinness, Concern for Physical
      Appearance, and Perception of Physical Appearance. There were significant
      differences among the groups in total PRFQ score, F(7,499)=2.76, P<.008, and the
      subscale score for Concern, F(7,499)=2.99, P<.004, with Dominicans, Venezuelans
      and Columbians having higher scores than White non-Hispanics and Central
      Americans/Mexicans. In addition, there was a significant difference in BMI,
      F(7,499)=2.70, P<.009. Both Puerto Ricans (24.27+0.81) and Venezuelans
      (24.66+1.00) had higher BMIs than White non-Hispanics (21.87+0.37), Cubans
      (21.99+0.24) and Brazilians (21.46+0.96). There was also a significant,
      F(7,498)=2.70, P<.009, difference among the groups in Ideal Body Image score.
      Puerto Ricans had the highest score and Brazilians the lowest. Acknowledging that
      differences in psychosocial risk factors exist among Hispanic females of diverse
      background can assist us in creating more targeted approaches for the prevention
      of potential eating disorders in this population.

PMID- 17174846
TI  - Readiness to change sugar sweetened beverage intake among college students.
AB  - The prevalence of obesity is a topic of concern in the United States, especially
      among children and young adults, and there is also a growing concern that sugared
      beverage consumption may contribute to increasing obesity rates. However, few
      studies to date have examined sugar sweetened beverage consumption trends in
      college students. This study investigated self-reported sugared beverage
      consumption, nutritional knowledge, and readiness to change sugar sweetened
      beverage intake in college students (N=201; 33% minority). On average, non
      overweight students reported significantly greater intake of sugared beverages
      than overweight students, and minority students reported greater consumption than
      Caucasians. A substantial majority of the sample (69%) reported that they had
      recently reduced their intake or were maintaining a reduction in intake. However,
      even those students indicating reduction in consumption reported intake of at
      least one sugar sweetened beverage daily. This suggests that high calorie
      beverage intake is a significant concern among young adult college-aged
      populations and that interventions targeting excess sugar sweetened beverage
      intake may have a role in obesity prevention efforts for this population.

PMID- 17174847
TI  - First-degree relative history of alcoholism in eating disorder inpatients:
      relationship to eating and substance use psychopathology.
AB  - OBJECTIVE: We examined the influence of family history of alcoholism on the
      presentation and course of inpatients with eating disorders (ED) by comparing ED
      behaviors, substance abuse behaviors, and psychopathology of patients with
      alcoholic first-degree relatives (AFDR+) to those without alcoholic first-degree
      relatives (AFDR-). METHOD: Female inpatients admitted to a specialty eating
      disorders service completed demographic, family history, behavioral, and
      psychological questionnaires (N=217). Body mass index (BMI) at admission and
      discharge, length of stay, and rates of weight gain were calculated. RESULTS:
      AFDR+ participants did not differ from AFDR- participants diagnostically, but
      AFDR+ participants did report higher lifetime frequencies of several ED and
      substance abuse behaviors. Measures of ED psychopathology and personality
      vulnerability were also elevated in the AFDR+ group. DISCUSSION: ED inpatients
      with a first-degree family history of alcoholism demonstrate increased
      psychopathology in eating behavior, substance use, and personality vulnerability
      domains. While the genetic diathesis for alcoholism is likely distinct from that
      for eating disorders, these findings suggest that first-degree relative history
      of alcoholism may nevertheless exert a negative influence on eating disorder
      behaviors.

PMID- 17174848
TI  - Trauma and multi-impulsivity in the eating disorders.
AB  - BACKGROUND: Multiple impulsive behaviours are common in the eating disorders, and
      multi-impulsive patients appear to do more poorly in treatment. However,
      comparatively little is known about the origins of multi-impulsivity in such
      cases. This study addresses the links between reported childhood trauma and multi
      impulsivity in the eating disorders, examining whether specific types of trauma
      are predictive of specific impulsive behaviours in this population. METHOD: The
      sample consisted of 102 individuals who met strict criteria for an eating
      disorder, and who were interviewed regarding trauma history and comorbid
      impulsive behaviours. RESULTS: Any reported history of childhood trauma was
      associated with a higher number of impulsive behaviours and with the presence of
      multi-impulsivity. Childhood sexual abuse was particularly important, and was
      associated with self-cutting, alcohol abuse, and substance abuse (amphetamines,
      cocaine, cannabis and 'other substances', including ketamine and
      benzodiazepines). DISCUSSION: These findings indicate the importance of
      considering the psychological consequences of trauma during both assessment and
      treatment of the eating disorders. In particular, eating-disordered women who
      report a history of childhood sexual abuse should be examined for a pattern of
      comorbid impulsive behaviours.

PMID- 17174849
TI  - Anatomy of a binge: food environment and characteristics of nonpurge binge
      episodes.
AB  - This secondary analysis prospectively examined nonpurge binge eating patterns in
      a naturalistic setting in 48 nonpurge binge eating women. Binge eating episodes
      were analyzed from 14-day food diaries to describe the binge and to determine how
      types of foods consumed and setting variables affected nonpurge binge eating
      women. Findings indicated that binge episodes occurred mostly during the lunch
      (27.1%) and dinner hours (45.8%) and on weekends (62.5%). Half of the binge
      episodes occurred in restaurants. The most common items consumed during binges
      were breads/pasta (64.6%), sweets (56.2%), high fat meat items (45.3%), and salty
      snacks (39.6%) while the predominant foods consumed during these binges were high
      fat meat items (29.2%), sweets (21.0%), and salty snacks (18.8%). Those who
      predominantly binged on sweets had significantly more binge days [t(46)=-2.8,
      p<.01]. Women who predominantly binged on fried meat had significantly higher
      body mass index (BMI) [t(46)=-2.8, p<.01]. A higher BMI was also associated with
      binging during meals rather than binging during snacks [t(46)=2.4, p<.05]. The
      results suggest that nonpurge binge eating patterns are more problematic during
      meal times.

PMID- 17174850
TI  - The development and validation of the weight management support inventory.
AB  - The purpose of this investigation was to develop and validate the Weight
      Management Support Inventory (WMSI). The WMSI assesses social support
      specifically for weight management. It quantifies the frequency and subjective
      helpfulness of supportive behaviors as well as examining four specific subtypes
      of support (emotional, instrumental, informational, and appraisal). The first
      stage of development (n=348) established the internal consistency (alpha) of the
      WMSI and also established the factor structure of the WMSI using confirmatory
      factor analysis. The second stage of development (n=237) demonstrated the
      construct, convergent, and discriminant validity of the WMSI. The WMSI provides a
      tool to allow future investigations to examine baseline levels of support for
      weight management and to verify changes in support via intervention.
      Additionally, the WMSI provides information that allows clinicians to tailor the
      social support component of weight management treatments to clients' individual
      needs.

PMID- 17174851
TI  - Development of a measure to assess invalidating childhood environments in the
      eating disorders.
AB  - OBJECTIVE: The role of childhood abuse is well recognised within the eating
      disorders. However, the impact of parental invalidation of the child's emotional
      needs has not been investigated. Such invalidation is potentially important
      because it appears to be associated with the difficulties in tolerating distress
      that are often seen in adults with eating disorders. This study aims to develop a
      measure of childhood invalidating environments (Invalidating Childhood
      Environments Scale; ICES). It also investigated the relationship between
      childhood experiences, levels of distress tolerance and eating pathology. METHOD:
      Seventy-three eating-disordered women and 62 non-eating-disordered women
      completed a newly developed measure of invalidating environments (ICES), the
      Eating Disorders Inventory, and a Distress Tolerance Scale. RESULTS: The ICES had
      acceptable psychometric and clinical validity. Women who scored highly on the
      ICES had greater levels of eating disturbance. Within the clinical sample, the
      data were compatible with a model where difficulties in tolerating distress
      partially mediate the relationship between perceived invalidation by the father
      and eating pathology. CONCLUSIONS: Parental invalidation is a potentially
      important construct in the eating disorders. This paper demonstrates that the
      ICES is a valid measure of that construct. This study suggests a clear framework
      for working with patients, where evidence of an invalidating childhood
      environment indicates a need to work with patients on their capacity to tolerate
      distress.

PMID- 17174852
TI  - Does binge eating disorder alter cortisol secretion in obese women?
AB  - It is still poorly determined whether the presence of Binge Eating Disorder (BED)
      would alter cortisol secretion in obese patients. We aimed at investigating
      levels of salivary cortisol (SC) in patients with and without BED. Forty seven
      (47) obese women between 30 and 65 years old were sequentially selected to
      participate in the study. The diagnosis of BED was assessed according to the
      Structured Clinical Interview for DSM-IV. Binge Eating Scale (BES) was used to
      assess binge severity. A trend toward a negative correlation was observed between
      SC and body mass index in the whole sample (p=0.06). The presence of BED was not
      associated with increased levels of SC. In women without BED, SC levels
      correlated inversely with BMI (p=0.01). On the other hand, in women with BED, SC
      levels correlated significantly with BES (p=0.01). Although obesity is associated
      with decreased levels of cortisol, this relationship may be lost in patients with
      BED. In patients with BED, binge eating severity may be a more relevant regulator
      of cortisol secretion than obesity itself.

PMID- 17174853
TI  - Core beliefs in dieters and eating disordered women.
AB  - OBJECTIVE: The current study aimed to investigate the difference in the levels of
      core beliefs between eating disordered women and those who showed milder forms of
      symptomatology. METHODS: Thirty-five eating disordered women, 16 symptomatic
      dieters, 39 normal dieters and 34 non-clinical comparison women completed
      questionnaires measuring eating symptomatology (Eating Disorders Inventory
      [EDI]), core beliefs (Young Schema Questionnaire [YSQ]), depression (The Beck
      Depression Inventory-II [BDI-II]) and self-esteem (Rosenberg Self-Esteem
      Inventory [RSE]). RESULTS: With the exception of Entitlement beliefs, there were
      significant differences in the levels of core beliefs across all four groups. In
      particular, symptomatic dieters and eating disordered women differed on 8 YSQ
      subscales despite showing very similar level of eating symptomatology.
      DISCUSSION: The current findings lend support to the discontinuity model that
      suggests that there are fundamental differences between women with a clinical
      eating disorder and those with milder eating psychopathology. The clinical and
      research implications of the present results were discussed.

PMID- 17174854
TI  - The method of delivery of nutrition and physical activity information may play a
      role in eliciting behavior changes in adolescents.
AB  - OBJECTIVES: Motivating adolescents to adopt proper nutrition and physical
      activity behaviors is important in this nation's fight to prevent obesity and
      chronic diseases. This study was conducted to determine which health education
      delivery method would elicit a greater behavior change. METHOD: The intervention
      was conducted in three schools (control, computer-based, and traditional
      education). RESULTS: Students who received the computer-based intervention showed
      increased knowledge (p<0.001), physical activity (p=0.001), self-efficacy
      (p<0.001), and social support (p<0.001), and decreased meals skipped (p<0.001).
      CONCLUSION: The computer-based group showed more positive behavior changes.
      However, future programs may be enhanced by including group discussion and
      individual feedback.

PMID- 17174855
TI  - Social and family correlates of eating problems and muscle preoccupation in young
      adolescents.
AB  - This study examined the unique contribution of a number of social and familial
      factors to body change strategies and eating problems in youths. A sample of non
      clinical adolescents aged 10 to 16 years (N=405) completed a modified version of
      the Children's Eating Attitudes Test (ChEAT) and questionnaires for measuring
      various social and familial factors that may play a role in the etiology of
      eating problems and muscle preoccupation. Regression analyses indicated that
      specific eating disorder-related factors (such as the encouragement of peers and
      parents to lose weight or to become more muscular) and more general factors (such
      as negative parental rearing behaviors and insecure attachment) made independent
      contributions to problem eating and muscle preoccupation in youths.

PMID- 17174856
TI  - Distress tolerance in the eating disorders.
AB  - OBJECTIVE: It is commonly noted that patients with eating disorders have
      difficulties in regulating emotional states. This construct is similar to the
      concept of distress tolerance, which has been identified as a problem in patients
      with impulsive disorders. However, the elements that make up distress tolerance
      are not clearly delineated, making it difficult to target treatment in relevant
      cases. This study aimed to develop a measure of distress tolerance, and to
      validate it clinically with the eating disorders. METHOD: The sample consisted of
      72 women with DSM-IV eating disorder diagnoses, and 62 women with no history of
      eating disorders. Each completed a newly developed measure of distress tolerance
      (the Distress Tolerance Scale; DTS) and the Eating Disorders Inventory. RESULTS:
      The DTS was made up of three scales, each with acceptable psychometric
      properties. Two of those scales differentiated the groups--the clinical women
      showed higher levels of 'Avoidance of affect', while the non-clinical women had
      higher scores in the 'Accept and manage' scale. Avoidance of affect was
      positively associated with unhealthy eating attitudes. CONCLUSIONS: It is
      important to examine both maladaptive and adaptive means of coping with affect in
      the eating disorders. Treatment strategies for modification of distress tolerance
      should address both the reduction of avoidance and the development of emotional
      management skills. Further research is needed to determine whether these findings
      are relevant to the presence of other impulsive behaviours in the eating
      disorders.

PMID- 17174857
TI  - Self-presentational motives in eating disordered behavior: a known groups
      difference approach.
AB  - OBJECTIVE: This study investigated the role of self-presentation motivation
      across three groups with known differences in disordered eating behavior.
      METHODS: Female participants (N=131) were currently in-treatment for an eating
      disorder (n=39), deemed at-risk (n=46), or not-at-risk for an eating disorder
      (n=46). All participants completed general and physique-specific measures of self
      presentation motivation. RESULTS: Results revealed significant moderate
      differences between groups. Those not-at-risk reported lower levels of self
      presentation motivation across all measures compared to those in the other
      groups. Those at-risk reported significantly lower scores across global measures
      of self-presentation motivation, but not physique-specific motives, than those in
      treatment. A discriminant function analysis demonstrated that self-presentation
      motivation correctly classified 63.4% of cases. DISCUSSION: Results suggest that
      self-presentation motives may be particularly salient for individuals at-risk or
      in-treatment for eating disordered behavior.

PMID- 17174858
TI  - Body image and eating disordered behavior in a community sample of Black and
      Hispanic women.
AB  - OBJECTIVE: The current study examined body image concerns and eating disordered
      behaviors in a community sample of Black and Hispanic women. In addition, this
      study explored whether there are ethnic differences in the correlates or in the
      prediction of body image concerns. METHOD: Participants were 120 (67 Black and 53
      Hispanic) women who responded to advertisements to participate in a study of
      women and health. Participants completed a battery of established self-report
      measures to assess body image, eating disordered behaviors, and associated
      psychological domains. RESULTS: Black and Hispanic women did not differ
      significantly in their self-reports of body image, eating disordered behaviors,
      or associated psychological measures. Comparisons performed separately within
      both ethnic groups revealed significant differences by weight status, with a
      general graded patterning of greater concerns in obese than overweight than
      average weight groups. In terms of predicting body image, multiple regression
      analyses testing a number of variables, including BMI, performed separately for
      Black and Hispanic women revealed that eating concern and depressive affect were
      significant predictors of body image concern for both groups. DISCUSSION:
      Overall, Black and Hispanic women differed little in their self-reports of body
      image, eating-disordered features, and depressive affect. Higher weight was
      associated with a general pattern of increased body image concerns and features
      of eating disorders in both groups and with binge eating in Black women. Eating
      concerns and depressive affect emerged as significant independent predictors of
      body image for both ethnic groups.

PMID- 17174859
TI  - Weight concerns in individuals with body dysmorphic disorder.
AB  - OBJECTIVE: To determine the prevalence of weight concerns in individuals with
      BDD, and to examine similarities and differences between those with and those
      without weight concerns. METHOD: We assessed 200 participants with BDD for
      clinically significant weight concerns and compared those with weight concerns
      (in addition to other body area concerns) to those without weight concerns on
      measures of BDD symptoms, other symptom severity, comorbidity, suicidality,
      functioning, and quality of life. RESULTS: 58 (29.0%) participants had weight
      concerns. Participants with weight concerns were younger, more likely to be
      female, and had more body areas of concern; a higher frequency of certain BDD
      behaviors, suicide attempts, and comorbidity; greater body image disturbance and
      depression; and poorer social functioning. The two groups were similar on other
      measures. DISCUSSION: Weight concerns in BDD deserve further study, as they
      appear relatively common and are associated with greater symptom severity and
      psychopathology in several domains.

PMID- 17174860
TI  - Religion, weight perception, and weight control behavior.
AB  - Religion's relationships with weight perception and weight control behavior were
      examined using data (3032 adults aged 25-74) from the National Survey of Midlife
      Development in the United States. Religion was conceptualized as denomination,
      religious attendance/practice, religious social support, religious commitment,
      religious application, and religious identity. Weight perception was
      conceptualized as underestimating body weight, overestimating body weight, and
      accurately assessing body weight. Respondents also reported whether they had
      engaged in any intentional weight loss (yes/no) in the last 12 months. Logistic
      regression was used, with significant results being set at a p-values of <.01 and
      <.05. Accurately assessing body weight was the reference category for all weight
      perception analyses. Women with greater religious commitment and men with greater
      religious application had greater odds of underestimating their body weight. This
      relationship remained significant, controlling for age, race/ethnicity,
      education, and income. Jewish women had greater odds of overestimating their body
      weight. There were no relationships between religion and weight control behavior.
      Relationships between religion, weight perception, and weight control behavior
      illustrate religion's multidimensionality.

PMID- 17174861
TI  - Reasons for wanting to lose weight: different strokes for different folks.
AB  - We assessed whether treatment seeking overweight and obese people citing
      differing reasons for wanting to lose weight also differed in psychosocial
      characteristics thought to impact on weight loss. Dieting motives, self-esteem,
      body image, number of dieting attempts in the past two years, and the primary
      reason for wanting to lose weight were assessed in 106 treatment seeking
      overweight and obese volunteers (mean (SD) body mass index 35.5 (5.7)kg/m2; age
      41.9 (10.8)y). Reasons for wanting to lose weight fell into three broad
      categories, with 35%, 50%, and 15% of the participants citing appearance, health,
      and mood, respectively. Participants citing health reasons were happier with
      their appearance than people citing mood or appearance reasons. Participants
      citing mood reasons had poorer self-image and self-esteem, a greater
      preoccupation with being overweight, and had attempted to diet more often than
      people citing appearance or health. The primary reason for overweight people
      seeking weight loss may reflect psychosocial differences that impact on
      successful weight loss. Identifying a person's reasons and motives for weight
      loss may help in tailoring dietary and psychological components of a weight loss
      program to the individual.

PMID- 17174862
TI  - Analysis of bulimic symptomatology across age and geographic locations.
AB  - The purpose of this study was two-fold: a) to investigate the relationship
      between age and bulimic symptoms among a sample of women with a broad age range;
      and b) to investigate the relationship between geographic location within the
      United States and bulimic symptoms. The sample consisted of 1807 female health
      professionals from six different states (NC, VA, OH, LA, TN, and MO). Analyses
      revealed that there were no differences between the age groups on bulimic
      symptoms. There were differences across geographic locations on bulimic symptoms,
      such that the South Atlantic (NC, VA) states reported the most bulimic symptoms.
      Findings suggest that age may not serve as a protective factor against bulimic
      symptoms as some previous studies have suggested. These findings also provide
      further evidence on the influence of environment on bulimic symptoms among a
      sample of women.

PMID- 17174864
TI  - Acute lumen overdilation improves outcome after brachytherapy of in-stent
      restenosis.
AB  - BACKGROUND: The aim of our study was to test the impact of acute lumen
      overdilation on neointimal hyperplasia and late lumen size after vascular
      brachytherapy for in-stent restenosis (ISR). METHODS: Forty-seven ISR lesions
      located in 47 coronary arteries in 44 consecutive patients underwent beta
      brachytherapy with serial intravascular ultrasound studies. Vessel, lumen, and
      stent cross-sectional area were measured at 1-mm steps. Based on an interpolated
      reference cross-sectional area, each cross section was assessed as overdilated
      (lumen cross-sectional area>interpolated reference cross-sectional area) or not
      overdilated (lumen cross-sectional area <interpolated reference cross-sectional
      area). RESULTS: Overall, 502 sections were overdilated and 673 sections were not.
      Overdilated sections had a larger final lumen cross-sectional area (8.02+/-1.98
      vs. 6.90+/-2.23 mm2, P<.001) and more recurrent neointimal hyperplasia (1.59+/
      2.17 vs. 0.31+/-1.79 mm2, P<.001), but a smaller follow-up area stenosis (-1.03+/
      32.99% vs. 22.15+/-20.75%, P<.001). This was especially true in smaller arteries
      (angiographic reference<3.0 mm) where larger follow-up lumen cross-sectional area
      and a corresponding smaller area stenosis were present (5.38+/-1.98 vs. 4.84+/
      1.88 mm2 and 6.90+/-31.57% vs. 28.61+/-21.86%, P<.01 and P<.001, respectively).
      CONCLUSIONS: Especially in small arteries, the strategy of acute lumen
      overdilation during balloon angioplasty prior to beta vascular brachytherapy
      treatment of ISR lesions has a favorable long-term result.

PMID- 17174865
TI  - Comparison of paclitaxel-eluting stent and sirolimus-eluting stent expansion at
      incremental delivery pressures.
AB  - OBJECTIVES: We sought to compare the adequacy of paclitaxel-eluting stent (PES)
      and sirolimus-eluting stent (SES) expansion based on intravascular ultrasound
      (IVUS) imaging criteria at conventional delivery pressures. METHODS: Forty-six
      patients underwent SES implantation and 42 patients underwent PES implantation
      for de novo native coronary lesions<33 mm in length with reference lumen
      diameters of 2.5-3.5 mm. Stents were serially expanded with gradual balloon
      inflations at 14 and 20 atm. IVUS imaging was performed prior to intervention and
      after each balloon inflation. Stent expansion (minimal stent cross-sectional
      area/reference lumen cross-sectional area) was measured. Inadequate stent
      expansion was defined using the MUSIC criteria (all struts apposed, no tissue
      protrusion, and final lumen cross-sectional area>80% of the reference or >90% if
      minimal lumen cross-sectional area was <9 mm2). RESULTS: The baseline
      characteristics of the two groups were similar except for shorter lesion length,
      larger mean lumen cross-sectional area, larger lumen diameter, and lower plaque
      burden in the PES group. Stent expansion was inadequate in 80% of patients with
      SES versus 63% of patients with PES at 14 atm, although this was not
      statistically significant. After 20 atm, 48% of patients with SES remained
      underexpanded as compared with 35% of patients with PES. CONCLUSION: Drug-eluting
      stents showed significant underexpansion by MUSIC criteria at conventionally used
      inflation pressures. Higher balloon inflations are required especially during
      deployment of a SES. IVUS guidance is recommended to ensure optimal results and
      outcomes with both stents.

PMID- 17174866
TI  - The effect of calcium dobesilate on venous function following saphenectomy in
      coronary artery bypass grafting.
AB  - BACKGROUND: The aim of this study was to determine whether prophylactic use of
      calcium dobesilate (CD) can improve venous function after saphenous vein harvest
      in coronary artery bypass graft (CABG). MATERIALS AND METHODS: A total of 100
      patients who underwent elective CABG were divided into four equal groups. In
      Group A, the greater saphenous vein (GSV) was harvested below the knee and, in
      Group B, through the knee till the groin. These patients remained untreated.
      Group C received CD in a dosage of 1500 mg po daily after the GSV was harvested
      below the knee. Group D received same dosage of CD after the GSV was harvested
      through the knee till the groin. Venous function of ipsilateral leg was evaluated
      clinically and by Doppler ultrasonography in the postoperative first week and
      second month. RESULTS: Clinical findings of venous insufficiency were observed
      with a similar rate between groups at both early and late periods. In Groups A
      and B, after 2 months, flow velocities decreased and reflux periods increased
      significantly. In groups C and D, treatment with CD for 2 months after
      saphenectomy resulted in a significant increase in flow velocities and a
      significant decrease in reflux periods. Patients in Groups B and D have
      significantly more impaired venous functions. CONCLUSION: Saphenectomy results in
      ipsilateral leg venous dysfunction, which seems to be unrelated to leg swelling
      and to be more prominent in patients with high-level saphenectomy. In addition,
      to be careful about the restriction of the saphenectomy procedure into the most
      appropriate level, prophylactic use of CD can prevent this deterioration when it
      was added to varice socks.

PMID- 17174867
TI  - Autologous bone marrow-derived progenitor cell myocardial delivery for recent
      myocardial infarction patients following early angioplasty: results from a pilot
      study.
AB  - PURPOSE: Cellular cardiomyoplasty is a potential therapeutic approach to
      preventing left ventricular remodeling after myocardial infarction and has shown
      encouraging results such as induction of neoangiogenesis and functional
      improvement of diseased hearts. We report the results of a pilot study on
      progenitor cells in five patients with acute myocardial infarction (AMI).
      MATERIALS AND METHODS: Patients with single-vessel disease who had their first
      episode of myocardial infarction and underwent angioplasty after 48 h (an average
      of 17 days following myocardial infarction) were included in the study.
      Mononuclear cells (MNCs) (1x10(7)) were isolated by Ficoll Hypaque method from 60
      ml of bone marrow (BM) obtained from the iliac crest of 5 patients (aspiration
      was performed under local anesthesia). The mean CD34 count was 1-4%. After
      confirming the patency of the affected vessel postangioplasty, cellular
      concentrate was injected into the affected artery in 3-ml boluses (three to four
      injections), with intermittent occlusion. RESULTS: The mean age of all five male
      patients was 48.6+13.7 years. At 1 year, five patients were asymptomatic, and one
      had Class II dyspnea on exertion. The results of an echocardiogram performed at 6
      months showed an improvement in ejection fraction (EF) from 35.3% to 43.13% and
      in fractional shortening from 24.75% to 28.33%. End-systolic volume decreased
      from 115.5 to 92.3 ml, end-diastolic volume decreased from 177.5 to 170 ml, and
      end-systolic dimensions also decreased from 4.26 to 4 mm, demonstrating positive
      left ventricular remodeling. Repeat echocardiogram at 1 year showed persistent
      improvement in EF. No adverse events were noted either before or after the
      procedure. CONCLUSION: The injection of autologous BM MNCs is a safe and
      efficacious therapy following early revascularization in AMI patients.

PMID- 17174868
TI  - Bone marrow-derived stem cell interactions with adult cardiomyocytes and skeletal
      myoblasts in vitro.
AB  - BACKGROUND AND OBJECTIVES: Secreted growth factors and cell-to-cell contact are
      both required to elicit cellular functions. We tested the hypothesis that bone
      marrow-derived growth factors, together with cell-to-cell contact between bone
      marrow-derived stem cells and cardiomyocytes or myoblasts, promote the
      proliferation of cardiomyocytes and myoblasts. METHODS: Human cardiomyocytes or
      skeletal myoblasts were cultured for 4 days in the presence of low and high
      concentrations of bone-marrow-derived mononuclear cell conditioned medium (MNC
      CM) or marrow stromal cell conditioned medium (MSC-CM). The concentrations of
      vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1
      (MCP-1), hepatocyte growth factor (HGF), and insulin-like growth factor-1 in
      their respective conditioned media were assayed by enzyme-linked immunosorbent
      assay. Stem cells were mixed with cardiomyocytes or skeletal myoblasts at a 1:1
      ratio and cultured for 7 days to assess the proliferation of these cells. In
      parallel experiments, equal numbers of various cell types were cultured alone.
      RESULTS: The concentrations of VEGF, MCP-1, and HGF increased in MNC-CM and MSC
      CM. MNC-CM showed no effect on cardiomyocyte proliferation. A low concentration
      of MSC-CM increased cardiomyocyte proliferation by 60% (P<.05). Low
      concentrations of MNC-CM or MSC-CM showed a trend toward an increased
      proliferation of myoblasts. A high concentration of either conditioned medium
      showed a toxic effect. In contact coculture, the proliferation of cardiomyocytes
      and MNC showed no synergistic effect; instead, there was some evidence of
      inhibition. The proliferation of cardiomyocytes and stromal cells showed an
      additive effect. Myoblasts in contact coculture with MNC or MSC showed no
      synergistic effect. CONCLUSION: These in vitro results suggest that paracrine
      effects may be the mechanism by which stromal cells become beneficial in cardiac
      therapy. MNC do not induce the proliferation of cardiomyocytes. Stem-cell
      secreted growth factors induce the proliferation of myoblasts, which is not
      influenced by cell-to-cell contact.

PMID- 17174869
TI  - Literature review: spontaneous coronary artery dissections.

PMID- 17174871
TI  - An audit of the use and complications of glycoprotein IIb/IIIa inhibitors in
      percutaneous coronary intervention against national UK standards.
AB  - Coronary thrombosis is a pivotal event in the pathogenesis of acute coronary
      syndromes and ischemic complications resulting from coronary intervention.
      Activation of the platelet glycoprotein (GP) IIb/IIIa receptor is the final
      common pathway leading to platelet aggregation, coronary thrombus formation, and
      myocardial ischemia. Inhibitors of platelet GP IIb/IIIa are potent agents to
      prevent progression to myocardial infarction and death. We prospectively surveyed
      the indications, frequency, and complications associated with the use of GP
      IIb/IIIa inhibitors in percutaneous coronary intervention in a tertiary center
      setting. A total of 170 patients underwent screening over a period of 6 weeks.
      One hundred four (61%) had coronary intervention, out of which eight (8%) had
      failed intervention. Glycoprotein IIb/IIIa inhibitors were used in 57 (55%)
      patients; 47 (45%) did not have any agent periprocedure. Eptifibatide was the
      most commonly used agent in 35 (33%), followed by abciximab in 19 (18%) and
      tirofiban in 3 (3%). Out of 57 patients in whom GP IIb/IIIa agents were used, 22
      (38%) had visible intracoronary thrombus, 22 (38%) had diffuse disease, 8 (14%)
      had complex intervention, and 5 (9%) had diabetes. The overall incidence of
      complications was not increased by the use of GP IIb/IIIa inhibitors; serious
      complications were rare with the use of GP IIb/IIIa agents; no stroke,
      thrombocytopenia, gastrointestinal bleed, or death was recorded. The overall use
      in emergency settings was not associated with increased complications.
      Bradycardia and vomiting were more common with abciximab group, whereas puncture
      site pain was commoner in eptifibatide group.

PMID- 17174870
TI  - Aldosterone antagonists: a new treatment option for patients with post-myocardial
      infarction heart failure.
AB  - Heart failure (HF) in association with acute myocardial infarction is an emerging
      clinical problem. The benefits of aldosterone blockade have now been extended,
      with the selective aldosterone antagonist eplerenone demonstrating reduced
      mortality compared to placebo, in patients with post-myocardial infarction HF.
      The evidence supporting this agent will be briefly reviewed, followed by a
      discussion on the clinical implications of aldosterone antagonists in this
      clinical setting.

PMID- 17174872
TI  - Case report: a very large dissection in the left anterior descending coronary
      artery of a 56-year-old man.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare condition that usually
      occurs in relatively young patients who are predominantly female. Seldom it could
      be a cause of acute myocardial ischemia leading to a sudden cardiac death. SCAD
      consists of intramural hematoma formation or, rarely, intimal tears that initiate
      and propagate the dissection in the vessel wall. In rare cases, the SCAD occurs
      in male patients. We report the case of a 56-year-old man with acute myocardial
      infarction who was successfully treated via systemic thrombolysis in a peripheral
      hospital. Associated conditions were thrombosis of right femoral artery in the
      past and high platelet count (800,000/mm3). After 1 month, elective coronary
      angiography revealed a very diffuse spiral dissection of the left anterior
      descending artery; hence, our choice of medical treatment consisted of double
      oral antiplatelet therapy (clopidogrel 75 mg plus aspirin 325 mg once daily).
      After a 2-year follow-up, there was absence of both angina and myocardial
      ischemia and there was a decrease in platelet count. Many strategies could be
      considered in patients with SCAD, such as PCI, bypass surgery, or conservative
      medical management. In general, the long-term prognosis of patients with SCAD is
      considered favorable if they survive the acute phase.

PMID- 17174873
TI  - Multidetector-row computed tomography diagnosis of coronary artery aneurysms and
      collateral vessel after Kawasaki disease in an adult.

PMID- 17174874
TI  - Effective prevention of massive periprocedural embolism during renal artery
      stenting.
AB  - We report the case of a massive embolism of atheromatous material during stenting
      of a tight renal artery stenosis, which was prevented by using a distal embolic
      protection device and aggressive aspiration of the blood through a guiding
      catheter. A 72-year-old man who was referred to our institution for coronary
      artery disease treated with coronary angioplasty underwent renal angiography
      which revealed a tight stenosis (99%) located at the ostium of the right renal
      artery extending for 15 mm into the main tract. The diameter of the artery was
      estimated to be 5.5 cm in the main tract, and the plaque had a soft appearance
      complicated by the presence of a thrombus (persistence of contrast agent in the
      plaque on selective renal angiography). Renal artery Doppler ultrasound and renal
      scintigraphy confirmed the need for renal revascularization. An embolus
      protection device (FilterWire EZ, Boston Scientific, Natick, MA, USA) was
      successfully opened distally to the stenosis after gentle predilation. After
      stent deployment (Genesis 5.5x18 mm, Cordis, J&J Medical, Miami Lakes, FL, USA),
      aggressive aspiration of the blood through the guiding catheter was performed. A
      large amount of embolic material with macroscopic particles was retrieved into
      the basket of the embolic protection device and in the blood aspirated with the
      guiding catheter. Good functional results were obtained on Doppler analysis of
      intrarenal blood flow, with a resistive index of 70. Despite the fact that the
      extensive use of embolic protection devices in renal artery stenting is still
      under discussion, this technique may be advisable in selected cases with
      favorable anatomy and high embolic risk, especially in patients with complex and
      hazy lesions.

PMID- 17174875
TI  - Failure of gated SPECT and echocardiography to detect large apical aneurysm
      secondary to hyperdynamic left ventricular wall at the aneurysm neck.
AB  - We present a patient with a history of coronary artery disease and exertional
      angina after an acute anterior myocardial infarction. Angiography and
      ventriculography revealed multivessel coronary artery disease and a large apical
      aneurysm. Echocardiography and gated SPECT studies were performed for further
      evaluation of ischemia and assessment of left ventricular function. Gated SPECT
      and echocardiography failed to detect a large apical aneurysm due to a
      hyperdynamic left ventricular wall at the neck of the aneurysm. This case
      demonstrates the importance of using multiple imaging modalities in the
      evaluation of ventricular function in the setting of coronary artery disease.

PMID- 17174876
TI  - Primary malignant lymphoma of the right atrium resulting in superior vena caval
      syndrome in an HIV-positive patient: depiction at multislice computed tomography
      and magnetic resonance imaging.
AB  - An HIV-positive 32-year-old male presenting with superior vena cava syndrome
      underwent multislice computed tomography (MSCT) and magnetic resonance imaging
      (MRI), which showed a large tumor in the right atrium, which extended to the
      superior vena cava. Pathologic examination revealed that the mass was consistent
      with B cell-type malignant lymphoma. The tumor size markedly decreased after the
      initiation of chemotherapy and patient recovery has been uneventful for 1 year.

PMID- 17174877
TI  - Simultaneous double-culprit in-stent thrombosis. Who is the guilty prisoner
      behind bars: drug-eluting stent, bare-metal stent, or indication for treatment?
AB  - BACKGROUND: The intrinsic thrombogeneity of stents was the historic limitation to
      their usage during the early phases of stenting. The risk of stent thrombosis has
      been minimized by the widespread use of platelet antiaggregation. Nowadays, the
      risk of subacute stent thrombosis is around 1%. Thrombotic risk depends on
      several factors, such as type of stent, complexity of lesion, and clinical
      picture. CASE REPORT: We present a case of recurrent acute in-stent thrombosis in
      a patient with mild antithrombin III (AT) deficiency despite the combined
      administration of clopidogrel and aspirin. CONCLUSION: In our patient, several
      factors, such as diabetes, AT deficiency, and the use of a paclitaxel-eluting
      stent, have contributed to the development of recurrent acute stent thrombosis.
      Although we were not able to identify the culprit factor, we should keep in mind
      that the deployment of a drug-eluting stent could be unsafe if it is not
      supported by a clear clinically oriented pathway that considers the overall
      condition of the patient since, in some cases, neither coronary lesions nor
      coronary stents are responsible for the negative outcome of patient therapy,
      which may be caused instead by incomplete or inadequate patient assessment.

PMID- 17174878
TI  - Endovascular filter-assisted treatment of atheroembolization from subclavian
      plaque.

PMID- 17174880
TI  - From glycomics to functional glycomics of sugar chains: Identification of target
      proteins with functional changes using gene targeting mice and knock down cells
      of FUT8 as examples.
AB  - Comprehensive analyses of proteins from cells and tissues are the most effective
      means of elucidating the expression patterns of individual disease-related
      proteins. On the other hand, the simultaneous separation and characterization of
      proteins by 1-DE or 2-DE followed by MS analysis are one of the fundamental
      approaches to proteomic analysis. However, these analyses do not permit the
      complete structural identification of glycans in glycoproteins or their
      structural characterization. Over half of all known proteins are glycosylated and
      glycan analyses of glycoproteins are requisite for fundamental proteomics
      studies. The analysis of glycan structural alterations in glycoproteins is
      becoming increasingly important in terms of biomarkers, quality control of
      glycoprotein drugs, and the development of new drugs. However, usual approach
      such as proteoglycomics, glycoproteomics and glycomics which characterizes and/or
      identifies sugar chains, provides some structural information, but it does not
      provide any information of functionality of sugar chains. Therefore, in order to
      elucidate the function of glycans, functional glycomics which identifies the
      target glycoproteins and characterizes functional roles of sugar chains
      represents a promising approach. In this review, we show examples of functional
      glycomics technique using alpha 1,6 fucosyltransferase gene (Fut8) in order to
      identify the target glycoprotein(s). This approach is based on glycan profiling
      by CE/MS and LC/MS followed by proteomic approaches, including 2-DE/1-DE and
      lectin blot techniques and identification of functional changes of sugar chains.

PMID- 17174881
TI  - Sex steroids, not FSH, influence bone mass.

PMID- 17174883
TI  - RNA interference: big applause for silencing in Stockholm.
AB  - Eight years ago, Craig Mello, Andrew Fire, and their coworkers provided the first
      demonstration that double-stranded RNA (dsRNA) triggers the gene-silencing
      technique that we now call RNA interference (RNAi). For this landmark discovery,
      Mello and Fire are honored with this year's Nobel Prize in Physiology or
      Medicine.

PMID- 17174884
TI  - A long time in the making--the Nobel Prize for RNA polymerase.
AB  - The 2006 Nobel Prize in Chemistry has been awarded to Roger Kornberg for
      elucidating the molecular basis of eukaryotic transcription. The prize caps a
      decades-long quest to unlock one of the central mysteries of molecular biology
      how RNA transcripts are assembled.

PMID- 17174885
TI  - In vino veritas: a tale of two sirt1s?
AB  - Resveratrol increases life span in lower organisms by activating the NAD(+)
      dependent histone deacetylase Sirt1. Studies by and now show that resveratrol
      promotes longevity and improves glucose homeostasis in mice by stimulating the
      Sirt1-mediated deacetylation of the transcriptional coactivator PGC-1alpha.

PMID- 17174886
TI  - A view to a kill: structure of the RNA exosome.
AB  - The exosome is a 3' to 5' exoribonuclease central to many cellular processes,
      including mRNA decay. now present the biochemical reconstitution and crystal
      structure of the eukaryotic exosome. This remarkable achievement provides key
      insights into the composition and assembly of the human and yeast exosomes,
      revealing functions of individual subunits.

PMID- 17174887
TI  - Multiple mechanisms of meiotic recombination.
AB  - In this issue, reveal that different meiotic recombination mechanisms predominate
      in fission yeast and budding yeast. Budding yeast usually form crossover
      recombinants through double Holliday junctions, whereas fission yeast
      unexpectedly appear to form crossover recombinants through single junctions.

PMID- 17174888
TI  - Sensory neurons link the nervous system and autoimmune diabetes.
AB  - The initial factors that trigger the autoimmune response against pancreatic
      islets in the nonobese diabetic (NOD) mouse are still unknown. In this issue of
      Cell, propose that a defect in a subset of sensory neurons innervating the
      pancreas plays a major role in initiating the chain of events that will lead to
      local inflammation, islet destruction, and autoimmune diabetes.

PMID- 17174889
TI  - A common progenitor at the heart of development.
AB  - Formation of the heart requires the coordinated functions of cardiac myocytes,
      smooth muscle cells, endothelial cells, and connective tissue elements. Several
      recent studies now reveal that these different cell types arise from a common
      progenitor (). These findings raise interesting questions about the lineage
      relationships of cardiovascular progenitor cell populations and suggest
      possibilities for cardiac repair in both congenital and acquired heart disease.

PMID- 17174890
TI  - Microtubule capture: a concerted effort.
AB  - Kinetochores direct attachment of chromosomes to microtubules of the mitotic
      spindle during cell division. Three recent studies in Cell, including one in this
      issue, reveal important new roles for two kinetochore protein complexes-Ndc80 and
      INCENP-Survivin-in establishing the correct attachment of chromosomes to spindle
      microtubules (Cheeseman et al., 2006, DeLuca et al., 2006 and Sandall et al.,
      2006).

PMID- 17174891
TI  - TRPV1+ sensory neurons control beta cell stress and islet inflammation in
      autoimmune diabetes.
AB  - In type 1 diabetes, T cell-mediated death of pancreatic beta cells produces
      insulin deficiency. However, what attracts or restricts broadly autoreactive
      lymphocyte pools to the pancreas remains unclear. We report that TRPV1(+)
      pancreatic sensory neurons control islet inflammation and insulin resistance.
      Eliminating these neurons in diabetes-prone NOD mice prevents insulitis and
      diabetes, despite systemic persistence of pathogenic T cell pools. Insulin
      resistance and beta cell stress of prediabetic NOD mice are prevented when
      TRPV1(+) neurons are eliminated. TRPV1(NOD), localized to the Idd4.1 diabetes
      risk locus, is a hypofunctional mutant, mediating depressed neurogenic
      inflammation. Delivering the neuropeptide substance P by intra-arterial injection
      into the NOD pancreas reverses abnormal insulin resistance, insulitis, and
      diabetes for weeks. Concordantly, insulin sensitivity is enhanced in trpv1(-/-)
      mice, whereas insulitis/diabetes-resistant NODxB6Idd4-congenic mice, carrying
      wild-type TRPV1, show restored TRPV1 function and insulin sensitivity. Our data
      uncover a fundamental role for insulin-responsive TRPV1(+) sensory neurons in
      beta cell function and diabetes pathoetiology.

PMID- 17174892
TI  - Single Holliday junctions are intermediates of meiotic recombination.
AB  - Crossing-over between homologous chromosomes facilitates their accurate
      segregation at the first division of meiosis. Current models for crossing-over
      invoke an intermediate in which homologs are connected by two crossed-strand
      structures called Holliday junctions. Such double Holliday junctions are a
      prominent intermediate in Saccharomyces cerevisiae meiosis, where they form
      preferentially between homologs rather than between sister chromatids. In sharp
      contrast, we find that single Holliday junctions are the predominant intermediate
      in Schizosaccharomyces pombe meiosis. Furthermore, these single Holliday
      junctions arise preferentially between sister chromatids rather than between
      homologs. We show that Mus81 is required for Holliday junction resolution,
      providing further in vivo evidence that the structure-specific endonuclease Mus81
      Eme1 is a Holliday junction resolvase. To reconcile these observations, we
      present a unifying recombination model applicable for both meiosis and mitosis in
      which single Holliday junctions arise from single- or double-strand breaks,
      lesions postulated by previous models to initiate recombination.

PMID- 17174894
TI  - Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous
      siRNAs in C. elegans.
AB  - We sequenced approximately 400,000 small RNAs from Caenorhabditis elegans.
      Another 18 microRNA (miRNA) genes were identified, thereby extending to 112 our
      tally of confidently identified miRNA genes in C. elegans. Also observed were
      thousands of endogenous siRNAs generated by RNA-directed RNA polymerases acting
      preferentially on transcripts associated with spermatogenesis and transposons. In
      addition, a third class of nematode small RNAs, called 21U-RNAs, was discovered.
      21U-RNAs are precisely 21 nucleotides long, begin with a uridine 5'-monophosphate
      but are diverse in their remaining 20 nucleotides, and appear modified at their
      3'-terminal ribose. 21U-RNAs originate from more than 5700 genomic loci dispersed
      in two broad regions of chromosome IV-primarily between protein-coding genes or
      within their introns. These loci share a large upstream motif that enables
      accurate prediction of additional 21U-RNAs. The motif is conserved in other
      nematodes, presumably because of its importance for producing these diverse,
      autonomously expressed, small RNAs (dasRNAs).

PMID- 17174893
TI  - A Bir1-Sli15 complex connects centromeres to microtubules and is required to
      sense kinetochore tension.
AB  - Proper connections between centromeres and spindle microtubules are of critical
      importance in ensuring accurate segregation of the genome during cell division.
      Using an in vitro approach based on the sequence-specific budding yeast
      centromere, we identified a complex of the chromosomal passenger proteins Bir1
      and Sli15 (Survivin and INCENP) that links centromeres to microtubules. This
      linkage does not require Ipl1/Aurora B kinase, whose targeting and activation are
      controlled by Bir1 and Sli15. Ipl1 is the tension-dependent regulator of
      centromere-microtubule interactions that ensures chromosome biorientation on the
      spindle. Elimination of the linkage between centromeres and microtubules mediated
      by Bir1-Sli15 phenocopies mutations that selectively cripple Ipl1 kinase
      activation. These findings lead us to propose that the Bir1-Sli15-mediated
      linkage, which bridges centromeres and microtubules and includes the Aurora
      kinase-activating domain of INCENP family proteins, is the tension sensor that
      relays the mechanical state of centromere-microtubule attachments into local
      control of Ipl1 kinase activity.

PMID- 17174895
TI  - Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by
      transcriptional interference.
AB  - Much of the genome is transcribed into long noncoding RNAs (ncRNAs). Previous
      data suggested that bithoraxoid (bxd) ncRNAs of the Drosophila bithorax complex
      (BX-C) prevent silencing of Ultrabithorax (Ubx) and recruit activating proteins
      of the trithorax group (trxG) to their maintenance elements (MEs). We found that,
      surprisingly, Ubx and several bxd ncRNAs are expressed in nonoverlapping patterns
      in both embryos and imaginal discs, suggesting that transcription of these ncRNAs
      is associated with repression, not activation, of Ubx. Our data rule out siRNA or
      miRNA-based mechanisms for repression by bxd ncRNAs. Rather, ncRNA transcription
      itself, acting in cis, represses Ubx. The Trithorax complex TAC1 binds the Ubx
      coding region in nuclei expressing Ubx, and the bxd region in nuclei not
      expressing Ubx. We propose that TAC1 promotes the mosaic pattern of Ubx
      expression by facilitating transcriptional elongation of bxd ncRNAs, which
      represses Ubx transcription.

PMID- 17174896
TI  - Reconstitution, activities, and structure of the eukaryotic RNA exosome.
AB  - The RNA exosome is a multisubunit 3' to 5' exoribonuclease complex that
      participates in degradation and processing of cellular RNA. To determine the
      activities and structure of the eukaryotic exosome, we report the reconstitution
      of 9-subunit exosomes from yeast and human and reconstitution of 10- and 11
      subunit exosomes from yeast. Comparative biochemical analysis between purified
      subunits and reconstituted exosomes using AU-rich, polyadenylated (poly[A]),
      generic, and structured RNA substrates reveals processive phosphorolytic
      activities for human Rrp41/Rrp45 and the 9-subunit human exosome, processive
      hydrolytic activities for yeast Rrp44 and the yeast 10-subunit exosome,
      distributive hydrolytic activities for Rrp6, and processive and distributive
      hydrolytic activities for the yeast 11-subunit exosome. To elucidate the
      architecture of a eukaryotic exosome, its conserved surfaces, and the structural
      basis for RNA decay, we report the X-ray structure determination for the 286 kDa
      nine-subunit human exosome at 3.35 A.

PMID- 17174897
TI  - Structure of the protein phosphatase 2A holoenzyme.
AB  - Protein Phosphatase 2A (PP2A) plays an essential role in many aspects of cellular
      physiology. The PP2A holoenzyme consists of a heterodimeric core enzyme, which
      comprises a scaffolding subunit and a catalytic subunit, and a variable
      regulatory subunit. Here we report the crystal structure of the heterotrimeric
      PP2A holoenzyme involving the regulatory subunit B'/B56/PR61. Surprisingly, the
      B'/PR61 subunit has a HEAT-like (huntingtin-elongation-A subunit-TOR-like) repeat
      structure, similar to that of the scaffolding subunit. The regulatory B'/B56/PR61
      subunit simultaneously interacts with the catalytic subunit as well as the
      conserved ridge of the scaffolding subunit. The carboxyterminus of the catalytic
      subunit recognizes a surface groove at the interface between the B'/B56/PR61
      subunit and the scaffolding subunit. Compared to the scaffolding subunit in the
      PP2A core enzyme, formation of the holoenzyme forces the scaffolding subunit to
      undergo pronounced conformational rearrangements. This structure reveals
      significant ramifications for understanding the function and regulation of PP2A.

PMID- 17174899
TI  - Quantitative proteomics analysis of the secretory pathway.
AB  - We report more than 1400 proteins of the secretory-pathway proteome and provide
      spatial information on the relative presence of each protein in the rough and
      smooth ER Golgi cisternae and Golgi-derived COPI vesicles. The data support a
      role for COPI vesicles in recycling and cisternal maturation, showing that Golgi
      resident proteins are present at a higher concentration than secretory cargo. Of
      the 1400 proteins, 345 were identified as previously uncharacterized. Of these,
      230 had their subcellular location deduced by proteomics. This study provides a
      comprehensive catalog of the ER and Golgi proteomes with insight into their
      identity and function.

PMID- 17174900
TI  - SnapShot: NF-kappaB signaling pathways.

PMID- 17174898
TI  - Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the
      subventricular neurogenic niche.
AB  - Neural stem cells are retained in the postnatal subventricular zone (SVZ), a
      specialized neurogenic niche with unique cytoarchitecture and cell-cell contacts.
      Although the SVZ stem cells continuously regenerate, how they and the niche
      respond to local changes is unclear. Here we generated nestin-creER(tm)
      transgenic mice with inducible Cre recombinase in the SVZ and removed
      Numb/Numblike, key regulators of embryonic neurogenesis from postnatal SVZ
      progenitors and ependymal cells. This resulted in severe damage to brain lateral
      ventricle integrity and identified roles for Numb/Numblike in regulating
      ependymal wall integrity and SVZ neuroblast survival. Surprisingly, the
      ventricular damage was eventually repaired: SVZ reconstitution and ventricular
      wall remodeling were mediated by progenitors that escaped Numb deletion. Our
      results show a self-repair mechanism in the mammalian brain and may have
      implications for both niche plasticity in other areas of stem cell biology and
      the therapeutic use of neural stem cells in neurodegenerative diseases.

PMID- 17174901
TI  - Social-insect fungus farming.

PMID- 17174902
TI  - The difference between organelles and endosymbionts.

PMID- 17174904
TI  - Males evolved from the dominant isogametic mating type.

PMID- 17174905
TI  - Asymmetric division: motor persistence pays off.
AB  - A new study shows that an antagonistic force model can explain a number of
      complex mitotic spindle movements in the first mitosis of the Caenorhabditis
      elegans embryo by simply assuming that cortical force generators become
      increasingly persistent in their interaction with microtubules during mitosis.

PMID- 17174907
TI  - Cellular biophysics: bacterial endospore, membranes and random fluctuation.
AB  - Purposeful motion of biological processes can be driven by Brownian motion of
      macromolecular complexes with one-sided binding biasing movement in one
      direction: a Brownian ratchet, now proposed to explain membrane motion during a
      phagocytosis-like process in bacteria.

PMID- 17174906
TI  - Social evolution: early production of deadly males by competing queens.
AB  - Males usually have little involvement in the dramas of social insect societies,
      but a newly identified Cardiocondyla ant species has been found to produce long
      lived, murderous males, even before the first workers, in a new form of queen
      queen competition.

PMID- 17174908
TI  - Oogamy: inventing the sexes.
AB  - The male-female dichotomy has evolved independently in nearly all lineages of
      multicellular organisms. Why this should be the case is still uncertain, but
      recent studies of mating-type genes in green algae open a promising new way to
      explore molecular-genetic aspects of the evolution of dichotomous sexes.

PMID- 17174909
TI  - Chemotaxis: Cofilin in the driver's seat.
AB  - A cell responds to a chemotactic signal by activating actin polymerization and
      forming a protrusion oriented towards the source. Recent work shows that the
      activity of cofilin, a protein that creates new barbed ends for actin filament
      elongation, amplifies and specifies the direction of the response in carcinoma
      cells.

PMID- 17174910
TI  - Algal genomics: exploring the imprint of endosymbiosis.
AB  - The nuclear genomes of photosynthetic eukaryotes are littered with genes derived
      from the cyanobacterial progenitor of modern-day plastids. A genomic analysis of
      Cyanophora paradoxa - a deeply diverged unicellular alga - suggests that the
      abundance and functional diversity of nucleus-encoded genes of cyanobacterial
      origin differs in plants and algae.

PMID- 17174911
TI  - Quality control: linking retrotranslocation and degradation.
AB  - Misfolded proteins in the ER require the p97 AAA ATPase for dislocation across
      the membrane prior to degradation by the cytosolic proteasome. The mechanism by
      which dislocated proteins are delivered to the proteasome from p97 is unclear,
      but recent studies suggest an important regulatory role for the protein ataxin-3.

PMID- 17174912
TI  - Growth regulation: a beginning for the hippo pathway.
AB  - A signaling pathway involving two protein kinases, Hippo and Warts, restricts the
      growth of imaginal discs in Drosophila. Four recent studies taken together show
      that the protocadherin Fat can regulate Warts in two different ways.

PMID- 17174913
TI  - Left-right asymmetry: making the right decision early.
AB  - A left-right asymmetry in neuronal function is specified surprisingly early
      during embryogenesis in Caenorhabditis elegans. Do early cues influence left
      right asymmetries in other animals? How are early cues remembered until late in
      development?

PMID- 17174914
TI  - Divergent roles for RalA and RalB in malignant growth of human pancreatic
      carcinoma cells.
AB  - BACKGROUND: The Ral guanine nucleotide-exchange factors (RalGEFs) serve as key
      effectors for Ras oncogene transformation of immortalized human cells. RalGEFs
      are activators of the highly related RalA and RalB small GTPases, although only
      the former has been found to promote Ras-mediated growth transformation of human
      cells. In the present study, we determined whether RalA and RalB also had
      divergent roles in promoting the aberrant growth of pancreatic cancers, which are
      characterized by the highest occurrence of Ras mutations. RESULTS: We now show
      that inhibition of RalA but not RalB expression universally reduced the
      transformed and tumorigenic growth in a panel of ten genetically diverse human
      pancreatic cancer cell lines. Despite the apparent unimportant role of RalB in
      tumorigenic growth, it was nevertheless critical for invasion in seven of nine
      pancreatic cancer cell lines and for metastasis as assessed by tail-vein
      injection of three different tumorigenic cell lines tested. Moreover, both RalA
      and RalB were more commonly activated in pancreatic tumor tissue than other Ras
      effector pathways. CONCLUSIONS: RalA function is critical to tumor initiation,
      whereas RalB function is more important for tumor metastasis in the tested cell
      lines and thus argues for critical, but distinct, roles of Ral proteins during
      the dynamic progression of Ras-driven pancreatic cancers.

PMID- 17174915
TI  - Keeping up with bats: dynamic auditory tuning in a moth.
AB  - Many night-flying insects evolved ultrasound sensitive ears in response to
      acoustic predation by echolocating bats . Noctuid moths are most sensitive to
      frequencies at 20-40 kHz , the lower range of bat ultrasound . This may
      disadvantage the moth because noctuid-hunting bats in particular echolocate at
      higher frequencies shortly before prey capture and thus improve their
      echolocation and reduce their acoustic conspicuousness . Yet, moth hearing is not
      simple; the ear's nonlinear dynamic response shifts its mechanical sensitivity up
      to high frequencies. Dependent on incident sound intensity, the moth's ear
      mechanically tunes up and anticipates the high frequencies used by hunting bats.
      Surprisingly, this tuning is hysteretic, keeping the ear tuned up for the bat's
      possible return. A mathematical model is constructed for predicting a linear
      relationship between the ear's mechanical stiffness and sound intensity. This
      nonlinear mechanical response is a parametric amplitude dependence that may
      constitute a feature common to other sensory systems. Adding another twist to the
      coevolutionary arms race between moths and bats, these results reveal unexpected
      sophistication in one of the simplest ears known and a novel perspective for
      interpreting bat echolocation calls.

PMID- 17174916
TI  - Queen-queen competition by precocious male production in multiqueen ant colonies.
AB  - Arriving earlier in the breeding area than his rivals may be beneficial for a
      male when females mate only once or during a short time span. The timing of a
      male's entrance is usually determined by the male himself, e.g., through
      returning early from his winter quarters or through accelerated larval
      development . Here, we document a surprisingly simple way of "first come, first
      served" in a species with local mate competition. In multiqueen colonies of a
      Cardiocondyla ant, mother queens make sure that their own sons are the first to
      monopolize mating with a large harem of female sexuals by producing extremely
      long-lived males early in colony life. Whereas queens in newly founded single
      queen colonies started to produce male and female sexuals only several weeks
      after the eclosion of their first worker offspring, queens in multiqueen colonies
      precociously reared sons long before the first female sexuals and even before the
      emergence of their first workers. These early males killed all later emerging
      males in the nest and mated with all female sexuals subsequently produced. Our
      data document that the patterns of growth and productivity of insect colonies are
      surprisingly flexible and can be turned upside down under appropriate selection
      pressures.

PMID- 17174917
TI  - Dual time scales for categorical decision making in auditory cortex.
AB  - Category formation allows us to group perceptual objects into meaningful classes
      and is fundamental to cognition. Categories can be derived from similarity
      relationships of object features by using prototypes or multiple exemplars, or
      from abstract relationships of features and rules . A variety of brain areas have
      been implicated in categorization processes, but mechanistic insights on the
      single-cell and local-network level are still rare and limited to the matching of
      individual objects to categories . For directional categorization of tone steps,
      as in melody recognition , abstract relationships between sequential events
      (higher or lower in frequency) have to be formed. To explore the neuronal
      mechanisms of this categorical identification of step direction, we trained
      monkeys for more than two years on a contour-discrimination task with multiple
      tone sequences. In the auditory cortex of these highly trained monkeys, we
      identified two interrelated types of neuronal firing: Increased phasic responses
      to tones categorically represented the reward-predicting downward frequency steps
      and not upward steps; subsequently, slow modulations of tonic firing predicted
      the behavioral decisions of the monkeys, including errors. Our results on
      neuronal mechanisms of categorical stimulus identification and of decision making
      attribute a cognitive role to auditory cortex, in addition to its role in signal
      processing.

PMID- 17174918
TI  - Sleeping functional group drives coral-reef recovery.
AB  - The world's coral reefs are in decline, with many exhibiting a phase shift from
      coral to macroalgal dominance . This change is often associated with habitat loss
      and overharvesting of herbivorous fishes, particularly parrotfishes and
      surgeonfishes . The challenge is to reverse this decline and enhance the
      resilience of coral-reef ecosystems . We demonstrate, by using a large-scale
      experimentally induced phase shift, that the rapid reversal from a macroalgal
      dominated to a coral- and epilithic algal-dominated state was not a result of
      herbivory by parrotfishes or surgeonfishes. Surprisingly, phase-shift reversal
      was primarily driven by a single batfish species (Platax pinnatus), a fish
      previously regarded as an invertebrate feeder. The 43 herbivorous fishes in the
      local fauna played only a minor role, suggesting that biodiversity may not offer
      the protection we hoped for in complex ecosystems. Our findings highlight the
      dangers faced by coral reefs and other threatened complex ecosystems: Species or
      functional groups that prevent phase shifts may not be able to reverse phase
      shifts once they occur. Nevertheless, reversal is possible. The critical issue is
      to identify and protect those groups that underpin the resilience and
      regeneration of complex ecosystems.

PMID- 17174919
TI  - Neural correlates of internal-model loading.
AB  - Skilled object manipulation requires knowledge, or internal models, of object
      dynamics relating applied force to motion , and our ability to handle myriad
      objects indicates that the brain maintains multiple models . Recent behavioral
      studies have shown that once learned, an internal model of an object with novel
      dynamics can be rapidly recruited and derecruited as the object is grasped and
      released . We used event-related fMRI to investigate neural activity linked to
      grasping an object with recently learned dynamics in preparation for moving it
      after a delay. Subjects also performed two control tasks in which they either
      moved without the object in hand or applied isometric forces to the object. In
      all trials, subjects received a cue indicating which task to perform in response
      to a go signal delivered 5-10 s later. We examined BOLD responses during the
      interval between the cue and go and assessed the conjunction of the two contrasts
      formed by comparing the primary task to each control. The analysis revealed
      significant activity in the ipsilateral cerebellum and the contralateral and
      supplementary motor areas. We propose that these regions are involved in internal
      model recruitment in preparation for movement execution.

PMID- 17174920
TI  - ApoE receptor 2 controls neuronal survival in the adult brain.
AB  - A central pathogenic feature of neurodegenerative diseases and neurotrauma is the
      death of neurons. A mechanistic understanding of the factors and conditions that
      induce the dysfunction and death of neurons is essential for devising effective
      treatment strategies against neuronal loss after trauma or during aging. Because
      Apolipoprotein E (ApoE) is a major risk factor for several neurodegenerative
      diseases, including Alzheimer's disease , a direct or indirect role of ApoE
      receptors in the disease process is likely. Here we have used gene targeting in
      mice to investigate possible roles of ApoE receptors in the regulation of
      neuronal survival. We demonstrate that a differentially spliced isoform of an
      ApoE receptor, ApoE receptor 2 (Apoer2), is essential for protection against
      neuronal cell loss during normal aging. Furthermore, the same splice form
      selectively promotes neuronal cell death after injury through mechanisms that may
      involve serine/threonine kinases of the Jun N-terminal kinase (JNK) family. These
      findings raise the possibility that ApoE and its receptors cooperatively regulate
      common mechanisms that are essential to neuronal survival in the adult brain.

PMID- 17174921
TI  - Competing selfish genetic elements in the butterfly Hypolimnas bolina.
AB  - Maternally inherited selfish genetic elements are common in animals . Whereas
      host genetics and ecology are recognized as factors that may limit the incidence
      of these parasites , theory suggests one further factor-interference with other
      selfish elements-that could affect their prevalence . In this paper, we show that
      spatial heterogeneity in the occurrence of the male-killing Wolbachia wBol1 in
      the tropical butterfly Hypolimnas bolina is caused by a second infection that can
      exclude the male-killer. We first provide evidence of a second Wolbachia strain,
      wBol2, present in most populations that do not carry the male-killer but rare or
      absent when the male-killer is present. Crossing data indicate that wBol2 in
      males induces cytoplasmic incompatibility to both uninfected and wBol1-infected
      females. The wBol2 infection can therefore not only spread through uninfected
      populations but also resist invasion by wBol1. Thus, we provide empirical support
      for the hypothesis that the incidence of particular selfish genetic elements can
      limit the presence of competing types.

PMID- 17174922
TI  - The Drosophila RASSF homolog antagonizes the hippo pathway.
AB  - Correct organ size is determined by the balance between cell death and
      proliferation. Perturbation of this delicate balance leads to cancer formation .
      Hippo (Hpo), the Drosophila ortholog of MST1 and MST2 (Mammalian Sterile 20-like
      1 and 2) is a key regulator of a signaling pathway that controls both cell death
      and proliferation . This pathway is so far composed of two Band 4.1 proteins,
      Expanded (Ex) and Merlin (Mer), two serine/threonine kinases, Hpo and Warts
      (Wts), the scaffold proteins Salvador (Sav) and Mats, and the transcriptional
      coactivator Yorkie (Yki). It has been proposed that Ex and Mer act upstream of
      Hpo, which in turn phosphorylates and activates Wts. Wts phosphorylates Yki and
      thus inhibits its activity and reduces expression of Yki target genes such as the
      caspase inhibitor DIAP1 and the micro RNA bantam. However, the mechanisms leading
      to Hpo activation are still poorly understood. In mammalian cells, members of the
      Ras association family (RASSF) of tumor suppressors have been shown to bind to
      MST1 and modulate its activity . In this study, we show that the Drosophila RASSF
      ortholog (dRASSF) restricts Hpo activity by competing with Sav for binding to
      Hpo. In addition, we observe that dRASSF also possesses a tumor-suppressor
      function.

PMID- 17174925
TI  - The lymphopenic mouse in immunology: from patron to pariah.
AB  - A recent surge of interest in the behavior of T and B cells in lymphopenic model
      systems has resurrected a certain cynicism about the validity of using such
      models to answer important immunological questions. Here we discuss this
      skepticism in a broader historical context.

PMID- 17174924
TI  - Two distinct surveillance mechanisms monitor meiotic chromosome metabolism in
      budding yeast.
AB  - Meiotic recombination is initiated by Spo11-generated DNA double-strand breaks
      (DSBs) . A fraction of total DSBs is processed into crossovers (CRs) between
      homologous chromosomes, which promote their accurate segregation at meiosis I
      (MI) . The coordination of recombination-associated events and MI progression is
      governed by the "pachytene checkpoint", which in budding yeast requires Rad17, a
      component of a PCNA clamp-like complex, and Pch2, a putative AAA-ATPase . We show
      that two genetically separable pathways monitor the presence of distinct meiotic
      recombination-associated lesions: First, delayed MI progression in the presence
      of DNA repair intermediates is suppressed when RAD17 or SAE2, encoding a DSB-end
      processing factor , is deleted. Second, delayed MI progression in the presence of
      aberrant synaptonemal complex (SC) is suppressed when PCH2 is deleted.
      Importantly, ZIP1, encoding the central element of the SC , is required for PCH2
      dependent checkpoint activation. Analysis of the rad17Deltapch2Delta double
      mutant revealed a redundant function regulating interhomolog CR formation. These
      findings suggest a link between the surveillance of distinct recombination
      associated lesions, control of CR formation kinetics, and regulation of MI
      timing. A PCH2-ZIP1-dependent checkpoint in meiosis is likely conserved among
      synaptic organisms from yeast to human .

PMID- 17174923
TI  - RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in
      response to genotoxic stress.
AB  - The Rho family of GTPases regulates many aspects of cellular behavior through
      alterations to the actin cytoskeleton . The majority of the Rho family proteins
      function as molecular switches cycling between the active, GTP-bound and the
      inactive, GDP-bound conformations . Unlike typical Rho-family proteins, the Rnd
      subfamily members, including Rnd1, Rnd2, RhoE (also known as Rnd3), and RhoH, are
      GTPase deficient and are thus expected to be constitutively active . Here, we
      identify an unexpected role for RhoE/Rnd3 in the regulation of the p53-mediated
      stress response. We show that RhoE is a transcriptional p53 target gene and that
      genotoxic stress triggers actin depolymerization, resulting in actin-stress-fiber
      disassembly through p53-dependent RhoE induction. Silencing of RhoE induction in
      response to genotoxic stress maintains stress fiber formation and strikingly
      increases apoptosis, implying an antagonistic role for RhoE in p53-dependent
      apoptosis. We found that RhoE inhibits ROCK I (Rho-associated kinase I) activity
      during genotoxic stress and thereby suppresses apoptosis. We demonstrate that the
      p53-mediated induction of RhoE in response to DNA damage favors cell survival
      partly through inhibition of ROCK I-mediated apoptosis. Thus, RhoE is anticipated
      to function by regulating ROCK I signaling to control the balance between cell
      survival and cell death in response to genotoxic stress.

PMID- 17174926
TI  - The ins and outs of MHC class II proteins in dendritic cells.
AB  - One more mechanism for regulating surface expression of MHC class II proteins in
      dendritic cells (an important process that regulates both tolerance and immunity)
      has been uncovered, polyubiquitination of Lys225 in the intracytoplasmic region
      and subsequent endocytosis and proteolysis (Omura-Hoshino et al., 2006; van Neil
      et al., 2006; Shin et al., 2006).

PMID- 17174927
TI  - Homing sweet homing: odyssey of hematopoietic stem cells.
AB  - The lineage relationship between the blood cells found in the developmentally
      successive hematopoietic organs has remained elusive. In this issue of Immunity,
      Murayama et al. (2006) track the migration of nascent hematopoietic stem cells in
      zebrafish from their site of origin to a newly described intermediate location.

PMID- 17174928
TI  - Maintaining hematopoietic stem cells in the vascular niche.
AB  - In this issue of Immunity, Sugiyama et al. (2006) provide evidence that most bone
      marrow hematopoietic stem cells (HSCs) reside in vascular niches containing
      reticular cells that secrete CXCL12, a chemokine that promotes HSC maintenance.

PMID- 17174929
TI  - Anergic B cells caught in the act.
AB  - Tolerance of B-lymphocytes to autoantigens is established by clonal deletion,
      receptor editing, and anergy. In this issue of Immunity, Merrell et al. (2006)
      have now identified that T3 "transitional" B cells in the spleen are not
      developmental intermediates but rather a major population of anergic B cells.

PMID- 17174930
TI  - Rulers over randomness: stroma cells guide lymphocyte migration in lymph nodes.
AB  - How is the amoeboid movement of lymphocytes in secondary lymphoid organs
      orchestrated? In this issue of Immunity, Bajenoff et al. (2006) demonstrate that
      stromal cell networks serve as guidance structures that direct and limit the
      migration of B and T cells in lymph nodes.

PMID- 17174931
TI  - Control of B lymphocyte apoptosis by the transcription factor NF-kappaB.
AB  - B cells maintain homeostasis by balancing cell viability and cell death. B
      lymphocytes are susceptible to mitochondria- and receptor-initiated cell death at
      various stages of peripheral differentiation and during immune responses. The
      inducible transcription factor NF-kappaB enhances cell viability by activating
      genes that counteract both cell-death pathways. This review uses characteristic
      features of NF-kappaB activation and downregulation to provide insight into the
      regulation of B cell apoptosis in the periphery. In particular, the temporal
      patterns of NF-kappaB induction, differences between Rel family members, and the
      intersection between canonical and noncanonical signaling pathways in keeping B
      cells alive are discussed.

PMID- 17174932
TI  - Molecular phylogeny of the filaria genus Onchocerca with special emphasis on
      Afrotropical human and bovine parasites.
AB  - Filarial parasites of the genus Onchocerca are found in a broad spectrum of
      ungulate hosts. One species, O. volvulus, is a human parasite that can cause
      severe disease (onchocerciasis or 'river blindness'). The phylogenetic
      relationships and the bionomics of many of the nearly 30 known species remain
      dubious. Here, the phylogeny of 11 species representing most major lineages of
      the genus is investigated by analysing DNA sequences from three mitochondrial
      genes (ND5, 12S and 16S rRNA) and portions of the intergenic spacer of the
      nuclear 5s rRNA. Special emphasis is given to a clade containing a yet unassigned
      specimen from Uganda (O. sp. 'Siisa'), which appears to be intermediate between
      O. volvulus and O. ochengi. While the latter can be differentiated by the O-150
      tandem repeat commonly used for molecular diagnostics, O. volvulus and O.
      sp.'Siisa' cannot be differentiated by this marker. In addition, a worm specimen
      from an African bushbuck appears to be closely related to the bovine O. dukei and
      represents the basal taxon of the human/bovine clade. At the base of the genus,
      our data suggest O. flexuosa (red deer), O. ramachandrini (warthog) and O.
      armillata (cow) to be the representatives of ancient lineages. The results
      provide better insight into the evolution and zoogeography of Onchocerca. They
      also have epidemiological and taxonomic implications by providing a framework for
      more accurate molecular diagnosis of filarial larvae in vectors.

PMID- 17174933
TI  - Human jaw and muscle modelling.
AB  - Dynamic mathematical modelling is an invaluable method to help understand the
      biomechanics of the anatomically and functionally complex masticatory system. It
      provides insight into variables which are impossible to measure directly such as
      joint loads and individual muscle tensions, and into physical relationships
      between jaw structure and function. Individual parameters can be modified easily
      to understand their influence on function. Our models are constructed with best
      available structural and functional data, and evaluated against human jaw
      behaviour. Image data provide hard and soft tissue morphology and the jaw's
      inertial properties. The drive to the system is provided by actuators which
      simulate active and passive jaw muscle properties. In whole-jaw modelling, muscle
      models which behave plausibly rather than mimic the ultra-structural cross-bridge
      interactions are common since they are computationally feasible. Whole-jaw models
      have recently incorporated flexible finite-elements to explore tissue distortion
      in the temporomandibular joint and tongue movements. Furthermore, the jaw has
      been integrated with laryngeal models to explore complex tasks such as
      swallowing. These dynamic models have helped better understand joint loading,
      movement constraints and muscle activation strategies. Future directions will
      include further incorporation of rigid and flexible model dynamics and the
      creation of subject-specific models to better understand the functional
      implications of pathology.

PMID- 17174934
TI  - Association of chlorophyll a/b-binding Pcb proteins with photosystems I and II in
      Prochlorothrix hollandica.
AB  - Action spectra for photosystem II (PSII)-driven oxygen evolution and of
      photosystem I (PSI)-mediated H(2) photoproduction and photoinhibition of
      respiration were used to determine the participation of chlorophyll (Chl) a/b
      binding Pcb proteins in the functions of pigment apparatus of Prochlorothrix
      hollandica. Comparison of the in situ action spectra with absorption spectra of
      PSII and PSI complexes isolated from the cyanobacterium Synechocystis 6803
      revealed a shoulder at 650 nm that indicated presence of Chl b in the both
      photosystems of P. hollandica. Fitting of two action spectra to absorption
      spectrum of the cells showed a chlorophyll ratio of 4:1 in favor of PSI.
      Effective antenna sizes estimated from photochemical cross-sections of the
      relevant photoreactions were found to be 192+/-28 and 139+/-15 chlorophyll
      molecules for the competent PSI and PSII reaction centers, respectively. The
      value for PSI is in a quite good agreement with previous electron microscopy data
      for isolated Pcb-PSI supercomplexes from P. hollandica that show a trimeric PSI
      core surrounded by a ring of 18 Pcb subunits. The antenna size of PSII implies
      that the PSII core dimers are associated with approximately 14 Pcb light
      harvesting proteins, and form the largest known Pcb-PSII supercomplexes.

PMID- 17174935
TI  - GAS6 is an estrogen-inducible gene in mammary epithelial cells.
AB  - To identify estrogen-responsive genes in mammary glands, microarray assays were
      performed. Twenty genes were found to be up-regulated while 16 genes were
      repressed in the 9h estrogen treated glands. The induction of GAS6, one of the
      genes up-regulated by estrogen, was confirmed by RNase protection assay.
      Furthermore, GAS6 was also demonstrated to be induced by estrogen in ER positive
      breast cancer cells. Analysis of GAS6 promoter revealed that GAS6 promoter was
      regulated by estrogen. An estrogen response element (ERE) was identified in the
      GAS6 promoter. Electrophoretic mobility shift assay revealed that ERalpha
      interacted with the ERE in the GAS6 promoter. Chromatin immunoprecipitation
      demonstrated that ERalpha was recruited to the GAS6 promoter upon estrogen
      stimulation. These results suggested that GAS6 is an estrogen target gene in
      mammary epithelial cells.

PMID- 17174936
TI  - Mibefradil-sensitive component involved in the plateau potential in submucosal
      interstitial cells of the murine proximal colon.
AB  - Submucosal interstitial cells of Cajal (ICC(SM)) produce plateau potentials
      comprised of initial fast and subsequent plateau components. The possible
      involvement of voltage-dependent Ca(2+) channels in plateau potentials was
      examined in ICC(SM) of the murine proximal colon. Increases in external K(+)
      concentration ([K(+)](o)) changed the rise rate of the initial component in a
      biphasic way, an increase in 10.6 or 15.3mM [K(+)](o) and a decrease in 20.0mM
      [K(+)](o). The rise rate of plateau potentials was significantly reduced by the
      application of 3 microM mibefradil or 100 microM Ni(2+) but not by 0.3 microM
      nifedipine. The inhibitory effect of mibefradil on the rise rate of plateau
      potentials was concentration-dependent with an IC(50) value of 1.0 microM. In
      conclusion, the initial phase of plateau potentials is partly due to the
      activation of T-type Ca(2+) channel in ICC(SM) from the murine proximal colon.

PMID- 17174937
TI  - Active transcription promotes single-stranded oligonucleotide mediated gene
      repair.
AB  - The lambda-Red-mediated recombination has been exploited as an efficient means
      for DNA manipulation. We previously reported that replication plays a pivotal
      role during this process. Replication direction dictates strand bias, such that
      single stranded oligonucleotide (SSO) with sequence corresponding to the nascent
      lagging strand directs higher levels of recombinant formation compared to its
      complementary SSO. In addition, the Escherichia coli methyl-directed mismatch
      repair system impedes efficient SSO-mediated site-specific gene repair. However,
      the role of transcription in determining strand bias and recombination efficiency
      is unclear. To address the potential role of transcriptional processes, we
      constructed plasmid substrates that harbor a mutant antibiotic reporter under the
      control of an inducible promoter. We found that transcription activation can
      promote recombinant formation to more than 10-folds whilst it has negligible
      effect on strand bias. Our findings provide evidence for a role of transcription
      in SSO-mediated gene repair process.

PMID- 17174938
TI  - Using amino acid and peptide composition to predict membrane protein types.
AB  - Membrane proteins play an important role in many biological processes and are
      attractive drug targets. Determination of membrane protein structures or
      topologies by experimental methods is expensive and time consuming. Effective
      computational method in predicting the membrane protein types can provide useful
      information for large amount of protein sequences emerging in the post-genomic
      era. Although numerous algorithms have addressed this issue, the methods of
      extracting efficient protein sequence information are very limit. In this study,
      we provide a method of extracting high order sequence information with the
      stepwise discriminant analysis. Some important amino acids and peptides that are
      distinct for different types of the membrane proteins have been identified and
      their occurrence frequencies in membrane proteins can be used to predict the
      types of the membrane proteins. Consequently, an accuracy of 86.5% in the cross
      validation test, and 99.8% in the resubstitution test has been achieved for a non
      redundant dataset, which includes type-I, type-II, multipass transmembrane
      proteins, lipid chain-anchored and GPI-anchored membrane proteins. The
      fingerprint features of the identified peptides in each membrane protein type are
      also discussed.

PMID- 17174939
TI  - FGF23 induces expression of two isoforms of NAB2, which are corepressors of Egr
      1.
AB  - Fibroblast growth factor 23 (FGF23) is a key humoral factor in phosphate
      homeostasis and skeletogenesis, though the nature of its intracellular signaling
      is still unclear. Recently, Egr-1, a zinc-finger transcription factor, was
      identified as an immediate early response gene of FGF23 in the kidney. We report
      here, that FGF23 induces not only Egr-1 but also two isoforms of NAB2, which are
      specific co-repressors of Egr-1. Both isoforms of NAB2 induced by FGF23 were
      localized in the nucleus and suppressed the transcriptional activity of Egr-1. A
      negative feedback loop established by Egr-1 and NAB2 may thus be involved in
      mediating the physiological effects of FGF23.

PMID- 17174940
TI  - Low-affinity uptake of the fluorescent organic cation 4-(4-(dimethylamino)styryl)
      N-methylpyridinium iodide (4-Di-1-ASP) in BeWo cells.
AB  - Understanding the mechanisms of transport processes in the placenta can improve
      the safety and efficacy of drug delivery during pregnancy. Functional studies of
      organic cation transporters (OCTs) are usually carried out using radioactivity,
      and a fluorescent marker would add flexibility to experimental methods. As a
      published substrate for OCT1 and OCT2, the fluorescent compound 4-(4
      (dimethylamino)styryl)-N-methylpyridinium iodide (4-Di-1-ASP) was chosen as a
      candidate for studying placental OCT function in BeWo cells. The expression of
      OCT1 and OCT2 was also investigated in BeWo cells, an established human
      choriocarcinoma trophoblastic cell line frequently used as an in vitro model of
      the rate-limiting barrier for maternal-fetal exchange of drugs and nutrients
      within the placenta. 4-Di-1-ASP was taken up into BeWo cells by a low-affinity,
      carrier-mediated process exhibiting a Km of 580+/-110 microM and Vmax of 97+/-9
      nmol/mg protein/30 min, and asymmetric transport was observed, with greater
      permeability in the apical to basolateral (maternal-to-fetal) direction. However,
      RT-PCR revealed no expression of OCT1 or OCT2 in either BeWo cells or primary
      cultured human cytotrophoblast cells, and OCT substrates such as TEA and choline
      did not inhibit the uptake of 4-Di-1-ASP. Although the uptake of this fluorescent
      compound in BeWo cells is not mediated by an OCT, the colocalization experiments
      with fluorescence microscopy and inhibition studies confirmed significant
      mitochondrial uptake of 4-Di-1-ASP. Transport of 4-Di-1-ASP into the nuclear
      region of BeWo cells was also observed, which is likely mediated by a nucleoside
      transporter.

PMID- 17174941
TI  - The changes of intracellular H2O2 are an important factor maintaining
      mitochondria membrane potential of antimycin A-treated As4.1 juxtaglomerular
      cells.
AB  - We investigated an involvement of ROS, such as H2O2 and O2- and GSH in the As4.1
      cell death by antimycin A and examined whether ROS scavengers rescue antimycin A
      induced As4.1 cell death and its mechanism. Levels of intracellular H2O2 and O2-
      were markedly increased in antimycin A-treated cells. Antimycin A reduced the
      intracellular GSH content. A ROS scavenger, Tiron down-regulated the production
      of intracellular H2O2. However, the reduction of intracellular H2O2 level did not
      change the apoptosis parameters, such as sub-G1 DNA content and annexin V
      binding. Interestingly, treatment of Tiron could partially prevent the loss of
      mitochondrial transmembrane potential (DeltaPsi(m)). Treatment of SOD and
      catalase also reduced the intracellular H2O2 and loss of mitochondrial
      transmembrane potential (DeltaPsi(m)) without reducing O2- level and apoptosis in
      antimycin A-treated As4.1 cells. All the ROS scavengers, SOD and catalase did not
      inhibit GSH depletion induced by antimycin A, resulting in failure of preventing
      the apoptosis. In addition, all the reagents including antimycin A did not induce
      any specific phase arrest of cell cycle in As4.1 cells. In summary, these results
      demonstrate that antimycin A generates potently ROS, H2O2 and O2- and induces the
      depletion of GSH content in As4.1 JG cells, and that Tiron, SOD and catalase
      inhibited partially the loss of mitochondrial transmembrane potential
      (DeltaPsi(m)) via the reduction of intracellular H2O2 level.

PMID- 17174942
TI  - Wnt7a overexpression delays beta-tubulin III expression in transgenic mouse
      embryos.
AB  - Wnt7a and HA-tagged Wnt7a have previously been shown to promote or delay neuronal
      differentiation respectively. In this study, we show that embryonic days 9.5 and
      10.5 transgenic mouse embryos overexpressing Wnt7a specifically in nestin
      positive neural stem/progenitor cells displayed a delay in neuronal
      differentiation, assayed by beta-tubulin III expression. Our results corroborate
      previous studies using HA-Wnt7a, and suggest a critical role for Wnt7a in control
      of neuronal progenitor maturation.

PMID- 17174943
TI  - The commissural pathway and cochlear nucleus bushy neurons: an in vivo
      intracellular investigation.
AB  - A direct commissural connection formed between cochlear nuclei allows information
      from the contralateral ear to rapidly influence the processing of the ascending
      auditory signal. Among the neuronal groups proposed to both receive, and
      contribute to, commissural input is the bushy cell population in the ventral
      cochlear nucleus (VCN). In this in vivo electrophysiological study we examine the
      intracellular recordings of bushy neurons during electrical stimulation of the
      contralateral cochlear nucleus (CN) for evidence of both their contribution to,
      and input from commissural projections. Activation of the commissural pathway
      revealed short-latency fast hyperpolarisation in 19.5% of the 41 bushy neurons
      examined. The hyperpolarising potentials were small in amplitude, displayed a
      highly variable time course between neurons, and in some cases were eliminated
      with injection of depolarising current. There was no indication of antidromic
      activity, or short-latency excitatory potentials. These results suggest that i)
      bushy neurons do not contribute projections to the commissural connection, and
      ii) a small portion of bushy neurons are hyperpolarised following commissural
      stimulation.

PMID- 17174944
TI  - Undersulfation of glycosaminoglycans induced by sodium chlorate treatment affects
      the progression of C6 rat glioma, in-vivo.
AB  - The stimulatory input of extracellular matrix (ECM) components has been
      implicated in the invasive properties of glioma cells. It has been demonstrated
      that undersulfation of glycosaminoglycans (GAGs) promoted by sodium chlorate (SC)
      treatment reduces C6 glioma cell proliferation and adhesion to ECM molecules, in
      vitro. In the present study, the authors investigated the involvement of GAG
      undersulfation in glioma cell growth in the brain parenchyma. The in-vitro
      treatment of C6 cells with SC and subsequent intracerebral inoculation in vehicle
      containing SC resulted in a reduced proportion of animals bearing glioma and a
      reduced tumor mass diameter. It also promoted longer animal survival.
      Intracerebral inoculation of SC-treated C6 cells in vehicle without SC or the SC
      treatment after intracerebral implantation of untreated C6 cells did not result
      in any reduction of tumor growth. Alterations in clinical, hematological and
      behavioral parameters in the open field were observed near the point of death
      when tumors presented a greater size. The results suggest an important role of
      GAGs in glioma growth which possibly affects cell proliferation and/or
      interactions with the normal tissue environment.

PMID- 17174945
TI  - Cryopreservation of porcine articular cartilage: MRI and biochemical results
      after different freezing protocols.
AB  - The objective of this study was to investigate the effects of cryopreservation on
      the components of articular cartilage (AC) matrix by utilizing magnetic resonance
      imaging (MRI) and biochemical assessments. Porcine AC (10mm osteochondral dowels)
      was collected into four groups - (1) phosphate buffered saline (PBS) control, (2)
      PBS snap frozen in liquid nitrogen, (3) slow-cooled in dimethyl sulfoxide (DMSO),
      and (4) slow cooled in PBS (in absence of DMSO). MRI results demonstrated three
      distinct zones in the cartilage. After exposure to ice formation during
      cryopreservation procedures, alterations in MRI determined matrix fixed charged
      density and magnetization transfer rate were noted. In addition, biochemical
      assays demonstrated significant alterations in chondroitin sulfate and
      hydroxyproline content over time without differences in hydration or DNA content.
      In conclusion, MRI was able to detect some changes in the intact cartilage matrix
      structure consistent with biochemical assessments after ice formation during
      cryopreservation of intact porcine AC. Furthermore, biochemical assessments
      supported some of these findings and changed significantly after incubating the
      cartilage matrix for 36-72 h in PBS in terms of chondroitin sulfate and
      hydroxyproline content.

PMID- 17174946
TI  - Hepatocyte growth factor activator inhibitor-1 (HAI-1) is essential for the
      integrity of basement membranes in the developing placental labyrinth.
AB  - Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a membrane-associated
      Kunitz-type serine protease inhibitor that regulates cell surface and
      extracellular serine proteases involved in tissue remodeling and tumorigenesis,
      such as HGFA, matriptase, prostasin and hepsin. We generated HAI-1 deficient
      mice, which died in utero due to placental defects. The HAI-1(-/-) placental
      labyrinth exhibited a complete failure of vascularization and a compact
      morphology of the trophoblast layer. Immunofluorescent staining of collagen IV
      and laminin and electron microscopy analysis revealed that this aberrant
      labyrinth architecture was associated with disrupted basement membranes located
      at the interface of chorionic trophoblasts and allantoic mesoderm. Unlike the
      placental labyrinth, basement membranes and vasculogenesis were normal in embryo
      and yolk sac. Therefore, basement membrane defects appear to be the underlying
      cause for the greatly impaired vascularization and trophoblast branching in HAI
      1(-/-) placentas. In wild-type placentas, the expression of matriptase and
      prostasin co-localized with their physiological inhibitor HAI-1 to the
      labyrinthine trophoblast cells in proximity to basement membranes. In HAI-1(-/-)
      placentas, both the localization and expression of the two proteases remained
      unchanged, implying uncontrolled proteolytic activities of the two enzymes. Our
      study demonstrates the important role of HAI-1 in maintaining the integrity of
      basement membrane most likely by regulating extracellular proteolytic activities
      during placental development.

PMID- 17174947
TI  - even-skipped has gap-like, pair-rule-like, and segmental functions in the cricket
      Gryllus bimaculatus, a basal, intermediate germ insect (Orthoptera).
AB  - Developmental mechanisms of segmentation appear to be varied among insects in
      spite of their conserved body plan. Although the expression patterns of the
      segment polarity genes in all insects examined imply well conserved function of
      this class of genes, expression patterns and function of the pair-rule genes tend
      to exhibit diversity. To gain further insights into the evolution of the
      segmentation process and the role of pair-rule genes, we have examined expression
      and function of an ortholog of the Drosophila pair-rule gene even-skipped (eve)
      in a phylogenetically basal insect, Gryllus bimaculatus (Orthoptera, intermediate
      germ cricket). We find that Gryllus eve (Gb'eve) is expressed as stripes in each
      of the prospective gnathal, thoracic, and abdominal segments and as a broad
      domain in the posterior growth zone. Dynamics of stripe formation vary among
      Gb'eve stripes, representing one of the three modes, the segmental, incomplete
      pair-rule, and complete pair-rule mode. Furthermore, we find that RNAi
      suppression of Gb'eve results in segmentation defects in both anterior and
      posterior regions of the embryo. Mild depletion of Gb'eve shows a pair-rule-like
      defect in anterior segments, while stronger depletion causes a gap-like defect
      showing deletion of anterior and posterior segments. These results suggest that
      Gb'eve acts as a pair-rule gene at least during anterior segmentation and also
      has segmental and gap-like functions. Additionally, Gb'eve may be involved in the
      regulation of hunchback and Kruppel expression. Comparisons with eve functions in
      other species suggest that the Gb'eve function may represent an intermediate
      state of the evolution of pair-rule patterning by eve in insects.

PMID- 17174948
TI  - Lipopolysaccharide-induced lung inflammation is inhibited by neutralization of GM
      CSF.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role
      in the pathogenesis of acute and chronic lung disease as a major regulator
      governing the functions of granulocyte and macrophage lineage populations.
      Chronic obstructive pulmonary disease (COPD) is a disease characterized by lung
      inflammation with accumulation of neutrophils and increased levels of pro
      inflammatory cytokines including GM-CSF in the patient's lungs. We used
      intranasal administration of lipopolysaccharide (LPS) to mice to induce a disease
      that resembles COPD with pulmonary inflammation, neutrophil recruitment and
      release of pro-inflammatory mediators in the bronchoalveolar lavage fluid of the
      diseased mice. 2 h prior to LPS administration, mice were systemically treated
      with the murine GM-CSF neutralizing antibody mAb 22E9 per intraperitoneal
      injection. Intranasal challenge with LPS-induced an increase of total cell number
      and of neutrophils in the bronchoalveolar lavage fluid. Elevated levels of tumor
      necrosis factor alpha (TNF-alpha), keratinocyte cytokine and macrophage
      inflammatory protein-2 (MIP-2) were also observed at this time point. GM-CSF was
      no longer detectable in bronchoalveolar lavage fluid at 24 h due to its early
      expression with a peak reached 6 h after LPS challenge. Pretreatment of mice with
      GM-CSF neutralizing antibody dose-dependently inhibited the accumulation of
      neutrophils and reduced TNF-alpha and MIP-2 protein levels in bronchoalveolar
      lavage fluid. These data suggest that neutralization of GM-CSF may represent a
      novel treatment modality for lung inflammation and in particular for COPD.

PMID- 17174950
TI  - A time course study demonstrating RNA stability in postmortem skin.
AB  - Knowledge of the factors regulating the rate of mRNA degradation, including
      postmortem delay, is important in determining the reliability of gene expression
      patterns in dermal tissue. Since RNA stability can be tissue dependent, this
      study evaluates the effect of postmortem interval on the integrity of total RNA
      or the levels of representative mRNA species in murine cutaneous tissue. Pieces
      of fresh skin tissue were excised for periods of 0-60 min from SKH-1 female
      hairless mice that were maintained at room temperature post-sacrifice. Total RNA
      was subsequently isolated and RNA integrity from each specimen was evaluated.
      Bioanalyzer profiles showed no apparent change in 28S/18S rRNA ratio or RNA
      integrity number at time points up to 60 min. Changes in mRNA expression levels
      of five selected genes were determined by real-time quantitative PCR. There were
      no statistical differences in the relative gene expressions of Ccnd1, Hif1alpha,
      cMyc and Cyr61 as a function of postmortem interval. Our data suggest that the
      molecular quality of cutaneous tissue is well preserved for at least 60 min after
      death, which can be regarded as important information for consideration of the
      order for tissue procurement in in vivo studies and acute ex vivo dermal studies.

PMID- 17174951
TI  - Cytotoxic granule disruption is a late event in chemotherapy-induced apoptosis in
      natural killer YT cells.
AB  - Cytotoxic lymphocytes such as Natural Killer (NK) cells can result in leukemias
      and lymphomas with aggressive clinical course. The cytoplasmic granules of NK
      cells contain molecules that cause apoptosis of their target cells. In this
      study, we examined changes of the cytotoxic granules of the Natural Killer cell
      line YT during Etoposide-induced apoptosis. Etoposide treatment resulted in an
      early upregulation of Fas and cytoplasmic release of mitochondrial cytochrome c.
      The cytotoxic granules remain intact in the early stages of apoptosis induction
      with no significant cytoplasmic release of granzyme B, which is one of the
      components of the cytotoxic granules. These results suggest that disruption of
      the cytotoxic granules is not involved in the induction stage of Etoposide
      induced apoptosis in the NK cell line YT.

PMID- 17174949
TI  - Endocannabinoids block status epilepticus in cultured hippocampal neurons.
AB  - Status epilepticus is a serious neurological disorder associated with a
      significant morbidity and mortality. Antiepileptic drugs such as diazepam,
      phenobarbital and phenytoin are the mainstay of status epilepticus treatment.
      However, over 20% of status epilepticus cases are refractory to the initial
      treatment with two or more antiepileptic drugs. Endocannabinoids have been
      implicated as playing an important role in regulating seizure activity and
      seizure termination. This study evaluated the effects of the major
      endocannabinoids methanandamide and 2-arachidonylglycerol (2-AG) on status
      epilepticus in the low-Mg(2+) hippocampal neuronal culture model. Status
      epilepticus in this model was resistant to treatment with phenobarbital and
      phenytoin. Methanandamide and 2-AG inhibited status epilepticus in a dose
      dependent manner with an EC(50) of 145+/-4.15 nM and 1.68+/-0.19 microM,
      respectively. In addition, the anti-status epilepticus effects of methanandamide
      and 2-AG were mediated by activation of the cannabinoid CB(1) receptor since they
      were blocked by the cannabinoid CB(1) receptor antagonist AM251. These results
      provide the first evidence that the endocannabinoids, methanandamide and 2-AG,
      are effective inhibitors of refractory status epilepticus in the hippocampal
      neuronal culture model and indicate that regulating the endocannabinoid system
      may provide a novel therapeutic approach for treating refractory status
      epilepticus.

PMID- 17174952
TI  - Altered distribution of heat shock protein 60 (Hsp60) with dysregulated
      expression of DHX32.
AB  - DHX32 has an overall similarity to the DHX family of RNA helicases but with a
      novel helicase domain and nuclear and mitochondrial localizations. The expression
      of DHX32 is highly regulated during lymphocyte activation and is dysregulated in
      lymphoid malignancies. In this study, we report our finding of an altered
      subcellular localization of heat shock protein 60 (Hsp60) in Jurkat-DHX32 cell
      line in which DHX32 is constitutively expressed. Two-dimensional gel
      electrophoresis followed by mass spectrometry, electron microscopic
      immunocytochemistry, and immunoblot analysis showed mainly cytoplasmic
      localization of Hsp60 in Jurkat-DHX32 cells instead of its mainly mitochondrial
      localization in control cells. No significant changes were detected in the
      mitochondrial ultra-structure and the mitochondrial membrane potential activity
      as a result of dysregulated DHX32 expression. The subcellular distribution of
      several mitochondrial proteins including cytochrome c, peroxiredoxin 3, manganese
      superoxide dismutase, Leucine-Rich PentatricoPeptide Repeat Cassette and the 49
      kDa subunit of the mitochondrial respiratory Complex I were similar in control
      and Jurkat-DHX32 cells ruling out non-specific cytoplasmic leakage of
      mitochondrial proteins. No significant changes in the expression of Hsp60
      transcript or total cellular protein were detected. These findings suggest that
      dysregulated expression of DHX32 might lead to as of yet unknown changes in
      mitochondrial homeostasis manifested by cytoplasmic redistribution of the
      molecular chaperon Hsp60.

PMID- 17174954
TI  - Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration.
AB  - The effect of tyrosine nitration on mammalian GS activity and stability was
      studied in vitro. Peroxynitrite at a concentration of 5 micro mol/l produced
      tyrosine nitration and inactivation of GS, whereas 50 micro mol/l peroxynitrite
      additionally increased S-nitrosylation and carbonylation and degradation of GS by
      the 20S proteasome. (-)Epicatechin completely prevented both, tyrosine nitration
      and inactivation of GS by peroxynitrite (5 micro mol/l). Further, a putative
      "denitrase" activity restored the activity of peroxynitrite (5 micro mol/l)
      treated GS. The data point to a potential regulation of GS activity by a
      reversible tyrosine nitration. High levels of oxidative stress may irreversibly
      damage and predispose the enzyme to proteasomal degradation.

PMID- 17174955
TI  - Characterisation of lipofuscin-like lysosomal inclusion bodies from human
      placenta.
AB  - A structural hallmark of lysosomes is heterogeneity of their contents. We
      describe a method for isolation of particulate materials from human placental
      lysosomes. After a methionine methyl ester-induced disruption of lysosomes and
      two density gradient centrifugations we obtained a homogeneous membrane fraction
      and another one enriched in particulate inclusions. The latter exhibited a yellow
      brown coloration and contained bodies lacking a delimiting membrane, which were
      characterised by a granular pattern and high electron density. The lipofuscin
      like inclusion materials were rich in tripeptidyl peptidase I, beta
      glucuronidase, acid ceramidase and apolipoprotein D and contained proteins
      originating from diverse subcellular localisations. Here we show that human term
      placenta contains lipofuscin-like lysosomal inclusions, a phenomenon usually
      associated with senescence in postmitotic cells. These findings imply that a
      simple pelleting of a lysosomal lysate is not appropriate for the isolation of
      lysosomal membranes, as the inclusions tend to be sedimented with the membranes.

PMID- 17174953
TI  - Targeted inactivation of synaptic HRG4 (UNC119) causes dysfunction in the distal
      photoreceptor and slow retinal degeneration, revealing a new function.
AB  - HRG4 (UNC119) is a photoreceptor protein predominantly localized to the
      photoreceptor synapses and to the inner segments to a lesser degree. A
      heterozygous truncation mutation in HRG4 was found in a patient with late onset
      cone-rod dystrophy, and a transgenic (TG) mouse expressing the identical mutant
      protein developed late onset retinal degeneration, confirming the pathogenic
      potential of HRG4. Recently, the dominant negative pathogenic mechanism in the TG
      model was shown to involve increased affinity of the truncated mutant HRG4 for
      its target, ARL2, which leads to a delayed decrease in its downstream target,
      mitochondrial ANT1, mitochondrial stress, synaptic degeneration, trans-synaptic
      degeneration, and whole photoreceptor degeneration by apoptosis. In this study,
      the mouse HRG4 (MRG4) gene was cloned and targeted to construct a knock-out (KO)
      mouse model of HRG4 in order to study the effects of completely inactivating this
      protein. The KO model was examined by genomic Southern blotting, Western
      blotting, immunofluorescence, funduscopy, LM and EM histopathology, ERG, and
      TUNEL analyses. The KO model developed a slowly progressive retinal degeneration,
      characterized by mottling in the fundus, mild thinning of the photoreceptor
      layer, and increase in apoptosis as early as 6 months, dramatic acceleration at
      approximately 17 months, and virtual obliteration of the photoreceptors by 20
      months. When compared to retinal degeneration in the TG model, significant
      differences existed in the KO consisting of more severe and early photoreceptor
      death without evidence of early synaptic and trans-synaptic degeneration as seen
      in the TG, confirmed by LM and EM histopathology, ERG, and Western blotting of
      synaptic proteins. The results indicated a dysfunction in the KO outside the
      synapses in the distal end of photoreceptors where MRG4 is also localized.
      Differences in the phenotypes of retinal degeneration in the KO and TG models
      reflect a dysfunction in the two opposite ends of photoreceptors, i.e., the
      distal inner/outer segments and proximal synapses, respectively, indicating a
      second function of MRG4 in the distal photoreceptor and dual functionality of
      MRG4. Thus, inactivation of MRG4 by gene targeting resulted in a retinal
      degeneration phenotype quite different from that previously seen in the TG,
      attesting to the multiplicity of MRG4 function, in addition to the importance of
      this protein for normal retinal function. These models will be useful in
      elucidating the functions of HRG4/MRG4 and the mechanism of slow retinal
      degeneration.

PMID- 17174956
TI  - Interaction of rice dwarf virus outer capsid P8 protein with rice glycolate
      oxidase mediates relocalization of P8.
AB  - Yeast two-hybrid and coimmunoprecipitation assays indicated that P8, an outer
      capsid protein of Rice dwarf phytoreovirus (RDV), interacts with rice glycolate
      oxidase (GOX), a typical enzyme of peroxisomes. Confocal immunofluorescence
      microscopy revealed that P8 was colocalized with GOX in peroxisomes. Time course
      analysis demonstrated that the localization of P8 in Spodoptera frugiperda cells
      changed from diffuse to discrete, punctuate inclusions during expression from 24
      to 48 h post inoculation. Coexpression of GOX with P8 may target P8 into
      peroxisomes, which serve as replication sites for a number of viruses. Therefore,
      we conclude that the interaction of P8 with the GOX of host cells leads to
      translocation of P8 into peroxisomes and we further propose that the interaction
      between P8 and GOX may play important roles in RDV targeting into the replication
      site of host cells. Our findings have broad significance in studying the
      mechanisms whereby viruses target appropriate replication sites and begin their
      replication.

PMID- 17174957
TI  - Role of pregnancy and parturition in induction of maternal behavior in prairie
      voles (Microtus ochrogaster).
AB  - In prairie voles (Microtus ochrogaster), most virgin females are infanticidal. To
      determine the onset of maternal responsiveness, female prairie voles were tested
      for maternal behavior as virgins and at different times throughout pregnancy.
      Female voles that were infanticidal as virgins by and large remained infanticidal
      throughout pregnancy. In contrast, about 30% of voles that were maternal as
      virgins became infanticidal during pregnancy. To test whether events associated
      with parturition facilitate the onset of maternal behavior, females had their
      litters delivered by Caesarean section within a day of expected delivery or were
      allowed to give birth naturally with sham surgery occurring shortly before or
      after birth. Females that gave birth naturally were fully maternal and did not
      attack unrelated pups, but females subjected to artificial delivery remained
      infanticidal. This suggests that events closely related to parturition are
      crucial for full development of maternal behavior in female prairie voles.

PMID- 17174958
TI  - In vivo measurement of translational stiffness of rabbit knees.
AB  - This paper describes the design, evaluation, and preliminary results of a
      specialized testing device and surgical protocol to determine translational
      stiffness of a rabbit knee, replicating the clinical anterior drawer test.
      Coronal-plane transverse pins are inserted through the rabbit leg, two in the
      tibia and one in the distal femur, to hold and reproducibly position the leg in
      the device for tests at multiple time points. A linear stepper motor draws the
      tibia upward then returns to the home position, and a load cell measures the
      resisting force; force-displacement knee stiffness is then calculated. Initial
      evaluation of this testing device determined the effects of preconditioning,
      intra-operator repeatability, rabbit-to-rabbit variability, knee flexion angle
      (90 degrees vs. 135 degrees ), and anterior cruciate ligament (ACL) sectioning
      (0%, 25%, 50%, 75%, 100%). Knee stiffness generally decreased as ACL sectioning
      increased. This testing device and surgical protocol provide an objective and
      efficient method of determining translational rabbit knee stiffness in vivo, and
      are being used in an ongoing study to evaluate the effect of knee instability
      (via partial to complete ACL sectioning) on the development of post-traumatic
      osteoarthritis.

PMID- 17174959
TI  - Mechanical properties of elastin along the thoracic aorta in the pig.
AB  - Understanding the mechanical environment of each component within the arterial
      wall is fundamental for understanding vascular growth and remodelling and for
      engineering artificial vascular conduits. We have investigated the mechanical
      status of arterial elastin by measuring the circumferential mechanical properties
      of purified elastin as function of position along the descending thoracic aorta
      of the pig. The tensile circumferential secant modulus, E(sec), measured in
      uniaxial mechanical tests, increased 30% (P<0.001), from a value of 0.88 MPa in
      the proximal tissue near the aortic arch to 1.14 MPa in the distal tissue near
      the diaphragm, indicating the stiffness of the elastin sample increased with
      position. Breaking stress was 54% higher in the distal tissue compared to the
      proximal (P<0.001), but the breaking stretch ratio did not change. E(sec)
      correlated with the ratio of radius to wall thickness measured in the no load
      state, r(nl)/h(nl), suggesting that the rise in stiffness was linked to ring
      morphology. The higher stiffness and strength of the distal tissue might be
      explained by a higher proportion of circumferentially oriented fibres in the
      distal tissue, which would indicate that the elastin meshwork in the thoracic
      aorta may become progressively anisotropic with distance from the heart. The
      ratio r(nl)/(h(nl)E (sec))rose only 7%, which suggests that the in vivo
      circumferential strain on the elastin may be constant along the pig thoracic
      aorta. The positional variation in elastin's properties should be taken into
      account in mechanical studies on purified elastin and in mathematical models of
      aorta mechanics.

PMID- 17174960
TI  - Unsupervised parameter optimization for automated retention time alignment of
      severely shifted gas chromatographic data using the piecewise alignment
      algorithm.
AB  - Simulated chromatographic separations were used to study the performance of
      piecewise retention time alignment and to demonstrate automated unsupervised
      (without a training set) parameter optimization. The average correlation
      coefficient between the target chromatogram and all remaining chromatograms in
      the data set was used to optimize the alignment parameters. This approach frees
      the user from providing class information and makes the alignment algorithm
      applicable to classifying completely unknown data sets. The average peak in the
      raw simulated data set was shifted up to two peak-widths-at-base (average
      relative shift=2.0) and after alignment the average relative shift was improved
      to 0.3. Piecewise alignment was applied to severely shifted GC separations of
      gasolines and reformate distillation fraction samples. The average relative
      shifts in the raw gasolines and reformates data were 4.7 and 1.5, respectively,
      but after alignment improved to 0.5 and 0.4, respectively. The effect of
      piecewise alignment on peak heights and peak areas is also reported. The average
      relative difference in peak height was -0.20%. The average absolute relative
      difference in area was 0.15%.

PMID- 17174961
TI  - 224 nm Deep-UV laser for native fluorescence, a new opportunity for biomolecules
      detection.
AB  - A new highly sensitive and compact 224 nm laser-induced native fluorescence
      (LINF) detector was developed using a new generation of deep-UV laser and an
      innovating elliptical flow cell. The use of deep-UV excitation at 224 nm allows
      to achieve fluorescence detection of an important range of molecules containing a
      single aromatic ring. The LINF detector was first evaluated in liquid
      chromatography. An improvement of a factor 500 over a conventional fluorimeter is
      reached with a limit of detection (LOD) of 1.5 pmole for ibuprofen. LODs were in
      the nanomole range for phenylalanine and in the picomole range for tyrosine and
      tryptophan. The LINF detector is able to detect the same levels of peptides
      concentrations as an ESI-ion trap spectrometer used in scan mode. In this
      application, LINF outperforms the UV detection at 214 or 254 nm and could be used
      with different additives with no noticeable effect on the detection.

PMID- 17174962
TI  - Lowering the concentration limits of detection by on-line solid-phase extraction
      capillary electrophoresis-electrospray mass spectrometry.
AB  - The use of solid-phase extraction coupled on-line to capillary electrophoresis
      using electrospray mass spectrometry detection (SPE-CE-ESI-MS) is described for
      the analysis of peptides in dilute solutions. A SPE microcartridge or analyte
      concentrator containing C(18) derivatized silica particles as the extraction
      sorbent was easily constructed near the inlet of the separation capillary using
      commercially available materials. The reversed-phase sorbent selectively retained
      the target peptides, enabling large volumes of the sample to be introduced
      (>100muL). The captured analytes were eluted in a small volume of an appropriate
      solution (20-50nL). This resulted in sample clean-up and concentration
      enhancement, with minimum sample handling. As the SPE-CE conditions were
      compatible with on-line ESI-MS detection, the potential for identifying and
      characterizing the preconcentrated analytes by SPE-CE-ESI-MS using a sheath-flow
      CE-ESI-MS interface is also shown. Using separation electrolytes containing N
      [carbamoylmethyl]-2-aminoethanesulfonic acid (ACES) at pH 7.4, an elution plug of
      80:20 (v/v) (25mM of formic acid in MeCN):H(2)O and a sheath liquid of 20mM of
      acetic acid in 50:50 (v/v) methanol:H(2)O the concentration limits of detection
      for the analyzed peptides in the positive ion mode were lowered to nanogram per
      milliliter levels. The systematic optimization of the operational parameters
      involved in the development of the SPE-CE method is described in detail, in order
      to promote robust and quantitative SPE-CE-ESI-MS analysis and facilitate the
      widespread use of the technique.

PMID- 17174963
TI  - Miniaturised selective pressurised liquid extraction of polychlorinated biphenyls
      from foodstuffs.
AB  - The feasibility of miniaturised pressurised liquid extraction (PLE) with in-cell
      purification and subsequent gas chromatography with micro-electron capture
      detection (GC-micro-ECD) for the determination of prioritary and toxic
      polychlorinated biphenyls (PCBs) in a variety of foodstuffs (fat contents in the
      range 22-49%, w/w, on a freeze-dried basis) has been investigated. After
      optimisation of the several experimental parameters affecting the efficiency of
      the selective PLE process, the developed method provided quantitative recoveries
      of the endogenous PCBs studied and complete fat elimination in a single step
      using n-hexane as extraction solvent. A total solvent volume of 3.5 mL was used
      for the two consecutive 7 min static PLEs of 100-mg samples. Detection limits
      using GC-micro-ECD were below 0.2 ng/g freeze dried sample for all 22 PCBs
      investigated in real-life foodstuffs, and the repeatability of the complete PLE
      plus GC-micro-ECD method as calculated for the analysis of the endogenous PCBs in
      general was better than 14%. Comparison of the miniaturised PLE method developed
      with either conventional Soxhlet extraction or matrix solid phase dispersion with
      subsequent (off-line) clean-up for the analysis of non-spiked samples showed that
      the efficiency of PLE was similar to or better (recoveries in the range 83-133%,
      as calculated for the endogenous analytes) than for the other two extraction
      methods assayed.

PMID- 17174964
TI  - Removal of basic dyes from aqueous solutions with a treated spent bleaching
      earth.
AB  - A spent bleaching earth from an edible oil refinery was treated by impregnation
      with a normal sodium hydroxide solution followed by mild thermal treatment (100
      degrees C). The obtained material (TSBE) was washed, dried, and characterized by
      X-ray diffraction, FTIR, SEM, BET, and thermal analysis. The clay structure was
      not apparently affected by the treatment and the impregnated organic matter was
      quantitatively removed. We have investigated the comparative sorption of
      safranine and methylene blue on this material, the spent bleaching earth (SBE),
      and the virgin bleaching earth (VBE). The kinetic results fit the pseudo-second
      order kinetic model and the Weber and Morris intraparticle diffusion model. The
      pH had no effect on the sorption efficiency. The sorption isotherms followed the
      Langmuir model for various sorbent concentrations with good values of the
      determination coefficient. A linear relationship was found between the calculated
      maximum removal capacity and the solid/solution ratio. A comparison between the
      results obtained with this material and those of the literature highlighted the
      low cost and the good removal capacity of treated spent bleaching earth.

PMID- 17174965
TI  - Relocation of active acetylcholinesterase to liposome-gel conjugate.
AB  - Relocation of a glycosylphosphatidylinositol (GPI)-anchored protein
      acetylcholinesterase (AChE) in its enzymatically active form from proteovesicles
      containing human erythrocyte ghost membrane proteins onto a liposome-gel
      conjugate was examined. Liposomes of 1,2-dimyristoylphosphatidylcholine (DMPC)
      were immobilized on Sephacryl S-1000 gel that was chemically modified to bear
      hydrophobic octyl moieties. Upon coincubation of the liposome-gel conjugate with
      freely suspended proteovesicles prepared from erythrocyte ghosts, 50% of the AChE
      left the proteovesicles and immobilized onto the liposome-gel conjugate in 18 h.
      When the proteovesicles were immobilized and interacted with freely suspended
      plain liposomes, approximately 2% of the AChE appeared in the liposome fraction.
      The relocation of AChE apparently possesses strong preference for the liposome
      gel conjugate, suggesting that the hydrophobic moieties on the gel could assist
      the relocation.

PMID- 17174966
TI  - Probing particle structure in waterborne pressure-sensitive adhesives with atomic
      force microscopy.
AB  - There is a need to know the nanostructure of pressure-sensitive adhesive (PSA)
      films obtained from waterborne polymer colloids so that it can be correlated with
      properties. Intermittent-contact atomic force microscopy (AFM) of an acrylic
      waterborne PSA film identifies two components, which can be attributed to the
      polymer and the solids in the serum (mainly surfactant). It is found that when
      the average AFM tapping force, F(av), is relatively low, the polymer particles
      appear to be concave. But when F(av) is higher, the particles appear to have a
      convex shape. This observation is explained by a height artefact caused by
      differences in the indentation depths into the two components that vary with the
      tapping amplitude and F(av). To achieve the maximum contrast between the polymer
      and serum components, F(av) should be set such that the indentation depths are as
      different as possible. Unlike what is found for the height images, the phase
      contrast images of the PSA do not show a reversal in contrast over the range of
      tapping conditions applied. The phase images are thus reliable in distinguishing
      the two components of the PSA according to their viscoelastic properties. At the
      surface of films dried at room temperature, the serum component is found in
      localized regions within permanent depression into the film.

PMID- 17174967
TI  - Monte Carlo simulations of surface energy of the open tetrahedral surface of 2:1
      type phyllosilicate.
AB  - Monte Carlo simulations were employed to investigate the surface energy of the
      open tetrahedral surface of 2:1-type phyllosilicate. Argon was selected as the
      probe molecule. The adsorption isotherm was simulated and the adsorption
      potential map was calculated. Both the density and energy distributions of
      adsorbed atoms were derived at different pressures to explore the adsorption
      mechanism. It is found that there exist two kinds of energetic sites: minima (
      15.5 kJ/mol) corresponding to the centers of six-membered rings and platform
      points (-8.0 kJ/mol) corresponding to the edges and vertexes of hexagons. They
      are primary and secondary adsorption sites, respectively. The implications for
      experiments and future studies are discussed. Current results are applicable for
      understanding surface energy properties of other clay minerals, since they have
      very similar basal surfaces.

PMID- 17174968
TI  - Thermodynamic aspects of sorption of Fe2+ onto unbleached Kraft fibres.
AB  - The sorption of Fe(2+) onto unbleached kraft fibre was investigated at different
      conditions such as pH, temperature, and concentrations. The sorption, which
      increased with concentration and temperature, followed the Langmuir isotherm.
      Thermodynamically, the process was spontaneous and endothermic. It was found that
      the precipitation of Fe(2+) was highly dependent on pH and reached 100% when pH
      exceeded approximately 8.

PMID- 17174969
TI  - Polymer-mediated chain-like self-assembly of functionalized gold nanoparticles.
AB  - We report an easy solution phase template-based method to assemble
      mercaptoundecanoic acid-functionalized gold nanoparticles (MUA-GNPs) along
      poly(ethylene oxide) (PEO) chains. Transmission electron microscopy (TEM) images
      show one-dimensional and two-dimensional chain-like sequences of GNPs resembling
      PEO chains. The progress of the assembly was monitored by the evaluation of
      surface plasmon resonance band of MUA-GNPs with time by UV-vis spectroscopy. The
      assembly process is a result of hydrogen bonding interaction between the ethereal
      oxygen of PEO and carboxylic acid group of MUA attached to GNPs surface, which
      was confirmed through FTIR spectroscopy. The interaction between PEO and MUA-GNPs
      was further confirmed by thermal analysis using differential scanning
      calorimetry.

PMID- 17174970
TI  - The adsorption-desorption process of bovine serum albumin on carbon nanotubes.
AB  - The aim of this work is to study the adsorption-desorption process of bovine
      serum albumin (BSA) on carbon nanotubes (CNT) by reflectometry. The effect of the
      surface properties was analyzed by comparing the behavior of BSA on silica. The
      experiments were performed by reflectometry at different BSA concentrations, at
      pH 3.0, 4.8, and 7.0 and at two ionic strengths. Protein desorption was induced
      by either dilution with buffer or the addition of SDS. The initial adsorption
      rate is controlled by the attachment of BSA molecules to the surface, and
      strongly diminishes at pH 7. Adsorption isotherms reflect the high affinity of
      BSA for both sorbent surfaces and reach well-defined plateau values that depend
      on the pH, being the highest at pH 4.8 on CNT. Experiments performed at different
      ionic strengths (NaCl added) showed a less pronounced effect. Dilution does not
      induce desorption on either surface however, the addition of SDS removes protein
      only from the silica surface.

PMID- 17174971
TI  - Egon Matijevic--"Mister Colloids".

PMID- 17174972
TI  - CD molecules 2006--human cell differentiation molecules.
AB  - The Human Leucocyte Differentiation Antigens Workshops (HLDA) have since 1984
      provided a forum for the characterization and study of leucocyte surface
      molecules and antibodies against them. HLDA devised the CD nomenclature, which is
      sanctioned by IUIS. The HLDA Council reviewed and modified the objectives of HLDA
      in 2004, and changed the name of the organization to Human Cell Differentiation
      Molecules (HCDM) to reflect the broader objectives. Workshop studies under the
      HCDM banner proceeded during 2005 and early 2006, culminating in a meeting in May
      2006. At that meeting the Council, acting as Nomenclature Committee, approved a
      number of new CD designations and changes to some pre-existing CD designations,
      which are summarized in this report.

PMID- 17174973
TI  - A small-scale serum-free liquid cell culture model of erythropoiesis to assess
      the effects of exogenous factors.
AB  - Anaemia is an important global health problem. Therefore, it is crucial to
      understand its pathophysiology in various genetic or infectious diseases where
      dyserythropoiesis is a key pathological feature. To this effect, reproducible and
      reliable models of erythropoiesis in vitro are much needed as investigative
      tools. We have developed a serum-free liquid culture model of erythropoiesis
      using human umbilical cord blood CD34(+) cells cultured in the cytokine
      combination, interleukin-3 (IL-3), IL-6, stem cell factor (SCF) and
      erythropoietin (Epo), over 14 days. We found that these culture conditions
      favored erythroid differentiation over the expansion of the more primitive
      erythroid precursors. With an initiating culture density of 5x10(4) cells per ml,
      the nucleated cell fold expansion increased from 7.9+/-3.9 (range 4.5 to 11.1)
      after 4 days to 2990.2+/-1936.1 (range 626.6 to 6912.0) after 14 days in culture.
      Day-14 burst-forming unit-erythroid (BFU-E) frequencies peaked at day 4 (24.0+/
      8.9%), with a marked decrease in BFU-E burst size as the cultures progressed.
      Time-course immunophenotypical profiles were characteristically erythroid with a
      decrease in CD34 expression (from 96.8+/-3.0% at day 0 to 0.8+/-0.8% at day 14),
      and a concomitant increase in the expression of erythroid-specific markers, CD36,
      glycophorin A (GpA) and CD71 (from 14.8+/-5.0%, 1.7+/-1.0% and 37.9+/-18.0% to
      93.0+/-7.0%, 82.1+/-14.0% and 95.7+/-3.0%, respectively). Morphological studies
      revealed the presence of normoblasts with the complete absence of reticulocytes
      and mature erythrocytes after 14 days in culture. Once the culture conditions
      were optimized, we scaled down our culture model from 24-well plate (large-scale)
      to 96-well plate cultures (small-scale). We found that the small-scale cultures
      compared favorably with their large-scale counterpart in terms of erythroid
      progenitor cell proliferation and differentiation, particularly at low CD34(+)
      initiating cell doses. By using tumor necrosis factor-alpha (TNF-alpha), a known
      inhibitor of erythropoiesis, we validated our model system and showed a dose
      dependent inhibition of erythroid differentiation with TNF-alpha in our cultures.
      Therefore, our results demonstrate a small-scale serum-free liquid culture model
      of erythropoiesis that is comparable with and complements our well-defined large
      scale model. Our system would prove useful for screening the effects of exogenous
      factors on erythropoiesis in vitro.

PMID- 17174974
TI  - Optimizing adult mesenchymal stem cells for heart repair.

PMID- 17174976
TI  - Tea catechins attenuate chronic ventricular remodeling after myocardial ischemia
      in rats.
AB  - Tea catechins have many biological functions; these effects are induced by the
      suppression of several inflammatory factors. However, the effects of catechins on
      ventricular remodeling after myocardial ischemia have not been well investigated.
      To test the hypothesis that catechins can attenuate chronic ventricular
      remodeling after myocardial ischemia, we performed oral administration of
      catechins into rat myocardial ischemia models. We analyzed the mechanisms using
      physiological, pathological and molecular examinations. Although severe
      myocardial fibrosis with enhancement of inflammatory factors were observed in the
      non-treated ischemia group on day 28, catechins attenuated these changes with
      suppressed NF-kappaB and matrix metalloproteinases without systemic adverse
      effects. Catechins are potent for the suppression of chronic ventricular
      remodeling after myocardial ischemia because they are critically involved in the
      suppression of several inflammatory genes.

PMID- 17174975
TI  - eNOS phosphorylation: a pivotal molecular switch in vasodilation and
      cardioprotection?

PMID- 17174977
TI  - Achieving specific RNA cleavage activity by an inactive splicing endonuclease
      subunit through engineered oligomerization.
AB  - Protein-protein interaction is a common strategy exploited by enzymes to control
      substrate specificity and catalytic activities. RNA endonucleases, which are
      involved in many RNA processing and regulation processes, are prime examples of
      this. How the activities of RNA endonucleases are tightly controlled such that
      they act on specific RNA is of general interest. We demonstrate here that an
      inactive RNA splicing endonuclease subunit can be switched "on" solely by
      oligomerization. Furthermore, we show that the mode of assembly correlates with
      different RNA specificities. The recently identified splicing endonuclease
      homolog from Sulfolobus solfataricus, despite possessing all of the putatively
      catalytic residues, has no detectable RNA cleavage activity on its own but is
      active upon mixing with its structural subunit. Guided by the previously
      determined three-dimensional structure of the catalytic subunit, we altered its
      sequence such that it could potentially self-assemble thereby enabling its
      catalytic activity. We present the evidence for the specific RNA cleavage
      activity of the engineered catalytic subunit and for its formation of a
      functional tetramer. We also identify a higher order oligomer species that
      possesses distinct RNA cleavage specificity from that of previously characterized
      RNA splicing endonucleases.

PMID- 17174978
TI  - Solution structure of the THAP domain from Caenorhabditis elegans C-terminal
      binding protein (CtBP).
AB  - The THAP (Thanatos-associated protein) domain is a recently discovered zinc
      binding domain found in proteins involved in transcriptional regulation, cell
      cycle control, apoptosis and chromatin modification. It contains a single zinc
      atom ligated by cysteine and histidine residues within a Cys-X(2-4)-Cys-X(35-53)
      Cys-X(2)-His consensus. We have determined the NMR solution structure of the THAP
      domain from Caenorhabditis elegans C-terminal binding protein (CtBP) and show
      that it adopts a fold containing a treble clef motif, bearing similarity to the
      zinc finger-associated domain (ZAD) from Drosophila Grauzone. The CtBP THAP
      domain contains a large, positively charged surface patch and we demonstrate that
      this domain can bind to double-stranded DNA in an electrophoretic mobility-shift
      assay. These data, together with existing reports, indicate that THAP domains
      might exhibit a functional diversity similar to that observed for classical and
      GATA-type zinc fingers.

PMID- 17174979
TI  - Differential receptor subunit affinities of type I interferons govern
      differential signal activation.
AB  - Type I interferons (IFNs) elicit antiviral, antiproliferative and immunmodulatory
      responses by binding to a shared cell surface receptor comprising the
      transmembrane proteins ifnar1 and ifnar2. Activation of differential response
      patterns by IFNs has been observed, suggesting that members of the family play
      different roles in innate immunity. The molecular basis for differential
      signaling has not been identified yet. Here, we have investigated the recognition
      of various IFNs including several human IFNalpha species, human IFNomega and
      human IFNbeta as well as ovine IFNtau2 by the receptor subunits in detail.
      Binding to the extracellular domains of ifnar1 (ifnar1-EC) and ifnar2 (ifnar2-EC)
      was monitored in real time by reflectance interference and total internal
      reflection fluorescence spectroscopy. For all IFNs investigated, competitive 1:1
      interaction not only with ifnar2-EC but also with ifnar1-EC was shown.
      Furthermore, ternary complex formation was studied with ifnar1-EC and ifnar2-EC
      tethered onto solid-supported membranes. These analyses confirmed that the
      signaling complexes recruited by IFNs have very similar architectures. However,
      differences in rate and affinity constants over several orders of magnitude were
      observed for both the interactions with ifnar1-EC and ifnar2-EC. These data were
      correlated with the potencies of ISGF3 activation, antiviral and anti
      proliferative activity on 2fTGH cells. The ISGF3 formation and antiviral activity
      correlated very well with the binding affinity towards ifnar2. In contrast, the
      affinity towards ifnar1 played a key role for antiproliferative activity. A
      striking correlation was observed for relative binding affinities towards ifnar1
      and ifnar2 with the differential antiproliferative potency. This correlation was
      confirmed by systematically engineering IFNalpha2 mutants with very high
      differential antiproliferative potency.

PMID- 17174980
TI  - Colour preference as evidence for the theories on the evolution of autumn
      colours.

PMID- 17174981
TI  - How does intraspecific density regulation influence metapopulation synchrony and
      persistence?
AB  - Intraspecific density regulation influences the synchronization of local
      population dynamics through dispersal. Spatial synchrony in turn may jeopardize
      metapopulation persistence. Joining results from previous studies suggests that
      spatial synchrony is highest at moderate over-compensation and is low at
      compensating and at very strong over-compensating density regulation. We
      scrutinize this supposition of a unimodal relationship using a process-based
      metapopulation model with explicit local population dynamics. We extend the
      usually studied range of density regulation to under-compensation and analyse
      resulting metapopulation persistence. We find peaks of spatial synchrony not only
      at over-compensatory but also under-compensatory density regulation and show that
      effects of local density compensation on synchrony follow a bimodal rather than
      unimodal relationship. Persistence of metapopulations however, shows a unimodal
      relationship with a broad plateau of high persistence from compensatory to over
      compensatory density regulation. This range of high persistence comprises both
      levels of low and high spatial synchrony. Thus, not synchrony alone jeopardizes
      metapopulation persistence, but only in interplay with high local extinction
      risk. The functional forms of the relations of density compensation with spatial
      synchrony and persistence are robust to increases in dispersal mortality,
      landscape dynamics, or density dependence of dispersal. However, with each of
      these increases the maxima of spatial synchrony and persistence shift to higher
      over-compensation and levels of synchrony are reduced. Overall, for over
      compensation high landscape connectivity has negative effects while for under
      compensation connectivity affects persistence positively. This emphasizes the
      importance of species life-history traits for management decisions with regard to
      landscape connectivity: while dispersal corridors are essential for species with
      under-compensatory density regulation, they may have detrimental effects for
      endangered species with over-compensation.

PMID- 17174982
TI  - Noise analysis of an ion channel in the cardiac myocyte--study based on a Markov
      model.
AB  - Mechanical contraction of a cardiac muscle cell is related to the electric
      activation of the plasma membrane. As in the neuron cell, inflow of the Na(+)
      ions across the cell membrane causes electric activation with amplitude of about
      100 mV. However, differently from the nerve cell, the action potential lasts a
      few hundred milliseconds before repolarization. Moreover, several types of K(+)
      channel such as the classical inward rectifier K(+) channel, the voltage
      dependent channel and others are responsible for the formation of the action
      potential. The mechanism of opening and closing the K(+) channels is not
      thoroughly elucidated. In the present paper, a four state Markov model with one
      open and three closed states is studied to obtain open and close probabilities of
      the gates constituting a specific ionic channel. The probability density
      functions of durations of opening and closing of the channel are also discussed.

PMID- 17174983
TI  - Structure of large arteries: orientation of elastin in rabbit aortic internal
      elastic lamina and in the elastic lamellae of aortic media.
AB  - This study was designed to further our understanding of the elastic
      ultrastructure of vessels. Scanning electron microscopy and transmission electron
      microscopy were used to study the histomorphologic properties of the elastic
      fibers of rabbit aorta after purification of the elastin by means of hot alkaline
      treatments. The elastic fibers of whole rabbit aorta samples were also studied
      using confocal microscopy. Morphological assessment revealed that the elastin
      fibers contained in the elastic lamellae of media are perpendicular to the blood
      flow, and that the elastic fibers of the internal elastic lamina are parallel to
      the luminal flow. In conclusion, the structure of the elastin making up the
      elastic lamellae of the media is oriented in such a way as to sustain the
      circumferential mechanical stress of pulsation. By contrast, the structure of the
      elastin fibers that make up the internal elastic lamina provides little
      mechanical support for the circumferential tension, but can support longitudinal
      loading and act as a fenestrated membrane.

PMID- 17174984
TI  - The breast cancer susceptibility allele CHEK2*1100delC promotes genomic
      instability in a knock-in mouse model.
AB  - Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer
      and possibly other cancer types. In particular, the CHEK2*1100delC polymorphic
      variant has been identified as a low-penetrance breast cancer susceptibility
      allele in breast cancer families with wild type BRCA1 and BRCA2. To better
      understand the molecular basis by which this allele increases risk for disease,
      we have generated a mouse in which the wild type CHEK2 (Chk2 in mouse) allele has
      been replaced with the 1100delC variant. Mouse embryo fibroblasts (MEFs) derived
      from these mice have an altered cell cycle profile in which a far greater
      proportion of cells are in S-phase and in G2 (4N) compared with wild type cells.
      The mutant cells show signs of spontaneous genomic instability as indicated by
      polyploidy and an increase in DNA double strand breaks.

PMID- 17174985
TI  - Transcriptional profiling for understanding the basis of mitochondrial
      involvement in disease and toxicity using the mitochondria-specific MitoChip.
AB  - It is well documented that mitochondrial dysfunction significantly contributes to
      a number of degenerative diseases, metabolic disorders, and drug- and chemical
      induced toxicities. Thus far, information gained by several molecular and
      biochemical techniques used to delineate the mechanism of impaired mitochondrial
      activity underlying different diseases and various toxicities is still limited
      due to their low throughput potential. Here, we describe the development of
      mitochondria-specific mouse oligonucleotide microarray and its potential to
      define mechanisms of disease progression and drug toxicities associated with
      mitochondrial dysfunction at both nuclear and mitochondrial genome level.

PMID- 17174986
TI  - Group I metabotropic glutamate receptor-induced Ca(2+)-gradients in rat
      superficial spinal dorsal horn neurons.
AB  - Here, we investigated changes in the free cytosolic Ca(2+) concentration
      ([Ca(2+)](i)), induced by the pharmacological activation of metabotropic
      glutamate receptors (mGluRs), in nociceptive neurons of the superficial spinal
      dorsal horn. Microfluorometric Ca(2+) measurements with fura-2 in a lumbar spinal
      cord slice preparation from young rats were used. Bath application of the
      specific group I mGluR agonist (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG)
      resulted in a distinct increase of [Ca(2+)](i) in most of the neurons in
      superficial dorsal horn. In contrast, activation of groups II or III mGluRs by
      DCG-IV or l-AP4, respectively, failed to evoke any significant change in
      [Ca(2+)](i). The effect of (S)-3,5-DHPG was mediated by both group I subtypes
      mGluR1 and mGluR5, since combined pre-treatment with the subtype antagonists (S)
      4-CPG and MPEP was necessary to abolish the [Ca(2+)](i) increase. Depleting
      intracellular Ca(2+) stores with CPA or inhibiting IP(3)-receptors with 2-APB,
      respectively, reduced the (S)-3,5-DHPG-evoked [Ca(2+)](i) increase significantly.
      Inhibition of voltage-dependent L-type Ca(2+) channels (VDCCs) by verapamil or
      nicardipine reduced the (S)-3,5-DHPG-induced [Ca(2+)](i) rise likewise. Thus, in
      rat spinal cord, (S)-3,5-DHPG enhances Ca(2+) signalling in superficial dorsal
      horn neurons, mediated by the release of Ca(2+) from IP(3)-sensitive
      intracellular stores and by an influx through L-type VDCCs. This may be relevant
      to the processing of nociceptive information in the spinal cord.

PMID- 17174987
TI  - The neural processing of moral sensitivity to issues of justice and care.
AB  - The empirical and theoretical consideration of ethical decision making has
      focused on the process of moral judgment; however, a precondition to judgment is
      moral sensitivity, the ability to detect and evaluate moral issues [Rest, J. R.
      (1984). The major components of morality. In W. Kurtines & J. Gewirtz (Eds.),
      Morality, moral behaviour, and moral development (pp. 24-38). New York, NY:
      Wiley]. Using functional magnetic resonance imaging (fMRI) and contextually
      standardized, real life moral issues, we demonstrate that sensitivity to moral
      issues is associated with activation of the polar medial prefrontal cortex,
      dorsal posterior cingulate cortex, and posterior superior temporal sulcus (STS).
      These activations suggest that moral sensitivity is related to access to
      knowledge unique to one's self, supported by autobiographical memory retrieval
      and social perspective taking. We also assessed whether sensitivity to rule-based
      or "justice" moral issues versus social situational or "care" moral issues is
      associated with dissociable neural processing events. Sensitivity to justice
      issues was associated with greater activation of the left intraparietal sulcus,
      whereas sensitivity to care issues was associated with greater activation of the
      ventral posterior cingulate cortex, ventromedial and dorsolateral prefrontal
      cortex, and thalamus. These results suggest a role for access to self histories
      and identities and social perspectives in sensitivity to moral issues, provide
      neural representations of the subcomponent process of moral sensitivity
      originally proposed by Rest, and support differing neural information processing
      for the interpretive recognition of justice and care moral issues.

PMID- 17174988
TI  - Visual attention capacity after right hemisphere lesions.
AB  - Recently there has been a growing interest in visual short-term memory (VSTM)
      including the neural basis of the function. Processing speed, another main aspect
      of visual attention capacity, has received less investigation. For both cognitive
      functions human lesion studies are sparse. We used a whole report experiment for
      estimation of these two parameters in 22 patients with right side stroke.
      Psychophysical performance was analyzed using Bundesen's [Bundesen, C. (1990). A
      theory of visual attention. Psychological Review, 97, 523-547] Theory of Visual
      Attention (TVA) and compared statistically to lesion location and size measured
      by MRI. Visual processing speed was impaired in the contralesional hemifield for
      most patients, but typically preserved ipsilesionally, even after large cortico
      subcortical lesions. When bilateral deficits in processing speed occurred, they
      were related to damage in the right middle frontal gyrus or leukoaraiosis. The
      storage capacity of VSTM was also normal for most patients, but deficits were
      found after severe leukoaraiosis or large strokes extending deep into white
      matter. Thus, the study demonstrated the importance of white-matter connectivity
      for both VSTM capacity and ipsilesional processing speed. The study also showed
      that lesions in a large region of the right hemisphere, including the putamen,
      insula, and inferior frontal cortex, do not lead to general deficits in the
      capacity of visual attention.

PMID- 17174989
TI  - Basal testosterone moderates responses to anger faces in humans.
AB  - Prior research [van Honk J, Tuiten A, Verbaten R, van den Hout M, Koppeschaar H,
      Thijssen J, de Haan E. Correlations among salivary testosterone, mood, and
      selective attention to threat in humans. Horm Behav 1999;36(1):17-24; van Honk J,
      Tuiten A, Hermans E, Putman P, Koppeschaar H, Thijssen J, Verbaten R, van Doornen
      L. A single administration of testosterone induces cardiac accelerative responses
      to angry faces in healthy young women. Behav Neurosci 2001;115(1):238-42.] showed
      relationships in humans between testosterone (T) and vigilance to facial
      expressions of anger, which are considered signals of an impending dominance
      challenge. In Study 1, we used a differential implicit learning task (DILT) (see
      [Schultheiss OC, Pang JS, Torges CM, Wirth MM, Treynor W. Perceived facial
      expressions of emotion as motivational incentives: evidence from a differential
      implicit learning paradigm. Emotion 2005;5(1):41-54.]) to investigate the degree
      to which subjects find anger faces reinforcing. In the DILT, separate sequences
      of actions were paired with presentations of anger faces, neutral faces or a
      blank screen. After training, performance on the three sequences was measured in
      the absence of face stimuli. Saliva was collected for T measurement. Higher T
      predicted better learning on sequences paired with sub-threshold (i.e., presented
      too fast for conscious awareness) anger faces, suggesting that T is related to
      reinforcing qualities of these faces. In Study 2, we examined whether morning or
      afternoon T better predicted attention and vigilance to anger faces. Participants
      were tested at 9:00 and 15:00. At each session, saliva was collected for T
      measurement, and participants completed a Stroop task and a dot-probe task [Mogg
      K, Bradley BP, Hallowell N. Attentional bias to threat: roles of trait anxiety,
      stressful events, and awareness. Q J Exp Psychol A 1994;47(4):841-64.] with
      facial expression stimuli. Morning (peak) T was a better predictor of responses
      to anger faces than afternoon T. Morning T predicted greater Stroop-like
      interference to sub-threshold anger faces, as well as attentional orienting away
      from sub-threshold anger faces. These effects were not present for joy faces or
      for supraliminal anger faces. T may generally decrease aversion to threatening
      stimuli, and/or may specifically facilitate approach towards signals of dominance
      challenge.

PMID- 17174990
TI  - Glutathione reductase activity and isoforms in leaves and roots of wheat plants
      subjected to cadmium stress.
AB  - The behavior of glutathione reductase (GR, EC 1.6.4.2) activity and isoforms were
      analyzed in wheat (Triticum aestivum L.) leaves and roots exposed to a chronic
      treatment with a toxic cadmium (Cd) concentration. A significant growth
      inhibition (up to 55%) was found in leaves at 7, 14 and 21 days, whereas roots
      were affected (51%) only after three weeks. Wheat plants grown in the presence of
      100microM Cd showed a time-dependent accumulation of this metal, with Cd
      concentration being 10-fold higher in roots than in leaves. Nevertheless, lipid
      peroxidation was augmented in leaves in all experiments, but not in roots until
      21 days. Cadmium treatment altered neither the GR activity nor the isoform
      pattern in the leaves. However, GR activity increased 111% and 200% in roots at 7
      and 14 days, respectively, returning to control levels after 21 days. Three GR
      isoforms were found in roots of control and treated plants, two of which were
      enhanced by Cd treatment at 7 and 14 days, as assessed by activity staining on
      native gels. The changes in the isoform pattern modified the global kinetic
      properties of GR, thereby decreasing significantly (2.5-fold) the Michaelis
      constant (K(m)) value for oxidized glutathione. Isozyme induction was not
      associated with an enhancement of GR mRNA and protein expression, indicating that
      post-translational modification could occur. Our data demonstrated that up
      regulation of GR activity by the induction of distinctive isoforms occurs as a
      defense mechanism against Cd-generated oxidative stress in roots.

PMID- 17174991
TI  - 7-Polyacylated delphinidin 3,7-diglucosides from the blue flowers of
      Leschenaultia cv. Violet Lena.
AB  - The triacyl anthocyanins, Leschenaultia blue anthocyanins 1 and 2 (LBAs 1 and 2)
      were isolated from the blue flowers of Leschenaultia R. Br. cv. Violet Lena
      (Goodeniaceae), in which LBA 1 was present as a dominant pigment. The structure
      of LBA 1 was elucidated to be delphinidin 3-O-[6-O-(malonyl)-beta-D
      glucopyranoside]-7-O-[6-O-(4-O-(6-O-(4-O-(beta-D-glucopyranosyl)-trans-caffeoyl)
      beta-D-glucopyranosyl)-trans-caffeoyl)-beta-D-glucopyranoside] by application of
      chemical and spectroscopic methods. Since LAB 2 was isolated in small amount, its
      structure was tentatively assigned as either delphinidin 3-(malonylglucoside)-7
      [(glucosyl-p-coumaroyl)-(glucosylcaffeoyl)-glucoside] or delphinidin 3-(malonyl
      glucoside)-7-[(glucosyl-caffeoyl)(glucosyl-p-coumaroyl)-glucoside]. This is the
      first report of the occurrence of 7-polyacylated anthocyanins in the family of
      Goodeniaceae, although others have been found in the families of the
      Ranunculaceae, Campanulaceae, and Compositae. Moreover, delphinidin 3-glycoside-7
      di-(glucosylcaffeoyl)-glucoside has been reported only in the flowers of
      Platycodon grandiflorum (Campanulaceae). From a chemotaxonomical viewpoint, the
      Goodeniaceae may be closely related to the Campanulaceae.

PMID- 17174992
TI  - Cytotoxic farnesyl glycosides from Pittosporum pancheri.
AB  - Bioassay guided purification of the ethanolic extract of the bark of New
      Caledonian Pittosporum pancheri Brongn. and Gris (Pittosporaceae) led to the
      isolation and characterization of two new farnesyl monoglycosides, pancherins A
      and B. The structure of these compounds were determined on the basis of
      spectroscopic studies. The new compounds displayed a significant activity in the
      in vitro cytotoxic assay against KB cancer cell line, and pancherin A inhibits
      weakly farnesyl protein transferase.

PMID- 17174993
TI  - Domestic violence: the Lebanese experience.
AB  - OBJECTIVES: To estimate the prevalence of domestic violence among women
      presenting to primary health care facilities in Lebanon; to identify presenting
      symptoms and responses to varied forms of violence; and to examine variables
      associated with domestic violence. STUDY DESIGN/METHODS: A cross-sectional survey
      of all women presenting to four primary health care centres in different
      geographic areas of Lebanon from September 2002 to October 2002. A questionnaire
      was administered in interview format. The following information was collected
      from participants: demographic characteristics, perceived health status, prior
      exposure and responses to domestic violence, and characteristics of the
      perpetrators. RESULTS: Of the 1418 participants, 494 (35%) reported experiencing
      domestic violence and 307 (22%) had family members who had been exposed to
      domestic violence. Among the women exposed to violence, verbal abuse or insult
      was most common (88%) followed by physical violence (66%); 57% reported their
      experiences to family, friends or authorities, whereas the remainder kept silent.
      Women who were exposed to domestic violence had higher frequencies of reported
      physical symptoms than those who were not exposed. Generally, the perpetrators
      were spouses who had demographic backgrounds comparable to their wives. Multiple
      regression analyses showed that women's education levels, work status, health
      status, and familial violence predicted domestic violence. CONCLUSIONS: Women
      readily talk about their abuse when asked. The rate of domestic violence is high
      among Lebanese women and is a significant health issue. Additional research is
      needed to better understand the extent of the problem and to develop more
      effective reporting methods.

PMID- 17174995
TI  - Xenoestrogens are potent activators of nongenomic estrogenic responses.
AB  - Studies of the nuclear transcriptional regulatory activities of non-physiological
      estrogens have not explained their actions in mediating endocrine disruption in
      animals and humans at the low concentrations widespread in the environment.
      However, xenoestrogens have rarely been tested for their ability to participate
      in the plethora of nongenomic steroid signaling pathways elucidated over the last
      several years. Here we review what is known about such responses in comparison to
      our recent evidence that xenoestrogens can rapidly and potently elicit signaling
      through nongenomic pathways culminating in functional endpoints. Both estradiol
      (E(2)) and compounds representing various classes of xenoestrogens
      (diethylstilbestrol, coumestrol, bisphenol A, DDE, nonylphenol, endosulfan, and
      dieldrin) act via a membrane version of the estrogen receptor-alpha on pituitary
      cells, and can provoke Ca(2+) influx via L-type channels, leading to prolactin
      (PRL) secretion. These hormones and mimetics can also cause the oscillating
      activation of extracellular regulated kinases (ERKs). However, individual
      estrogen mimetics differ in their potency and temporal phasing of these
      activations compared to each other and to E(2). It is perhaps in these ways that
      they disrupt some endocrine functions when acting in combination with
      physiological estrogens. Our quantitative assays allow comparison of these
      outcomes for each mimetic, and let us build a detailed picture of alternative
      signaling pathway usage. Such an understanding should allow us to determine the
      estrogenic or antiestrogenic potential of different types of xenoestrogens, and
      help us to develop strategies for preventing xenoestrogenic disruption of
      estrogen action in many tissues.

PMID- 17174996
TI  - Phenylalanine(90) and phenylalanine(93) are crucial amino acids within the
      estrogen binding site of the human UDP-glucuronosyltransferase 1A10.
AB  - Human UDP-glucuronosyltransferase 1A10 has been identified as the major isoform
      involved in the biotransformation of a wide range of phenolic substrates,
      including native estrogens and their oxidized metabolites. Our recent studies
      point to the F(90)-M(91)-V(92)-F(93) amino acid motif of UGT1A10, which was
      identified using photoaffinity labeling followed by LC-MS/MS analysis, as a key
      determinant of the binding of phenolic substrates. In this report, we have
      evaluated the role of F(90), V(92), and F(93) in the recognition of estrogens by
      UGT1A10 using site-directed mutagenesis. Kinetic studies using five mutants
      revealed that F(90) and F(93) are critical residues for the recognition of all
      estrogen substrates. The substitution of F(90) with alanine totally abolished the
      activity of this enzyme toward all the estrogens investigated. Overall,
      sequential removal for the aromatic ring (F to L) and of the hydrophobic chain (F
      to A and V to A) from amino acids 90, 92, and 93 effectively alters estrogen
      recognition. This demonstrates that individual features of the native and
      hydroxylated estrogens determine the specific binding properties of the compound
      within the binding site of the human UGT1A10 and the mutants. The resulting
      activities are completely abolished, unchanged, increased, or decreased depending
      on the structures of both the mutant and the substrate. The novel identification
      of UGT1A10 as the major isoform involved in the glucuronidation of all estrogens
      and the discovery of the importance of the FMVF motif in the binding of steroids
      will help to elucidate the molecular mechanism of glucuronidation, resulting in
      the design of more effective estrogen-based therapies.

PMID- 17174998
TI  - Paroxetine-induced apoptosis in human osteosarcoma cells: activation of p38 MAP
      kinase and caspase-3 pathways without involvement of [Ca2+]i elevation.
AB  - Selective serotonin reuptake inhibitors (SSRIs), a group of antidepressants, are
      generally used for treatment of various mood and anxiety disorders. There has
      been much research showing the anti-tumor and cytotoxic activities of some
      antidepressants; but the detailed mechanisms were unclear. In cultured human
      osteosarcoma cells (MG63), paroxetine reduced cell viability in a concentration-
      and time-dependent manner. Paroxetine caused apoptosis as assessed by propidium
      iodide-stained cells and increased caspase-3 activation. Although immunoblotting
      data revealed that paroxetine could activate the phosphorylation of extracellular
      signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen
      activated protein kinase (p38 MAPK), only SB203580 (a p38 MAPK inhibitor)
      partially prevented cells from apoptosis. Paroxetine also induced [Ca(2+)](i)
      increases which involved the mobilization of intracellular Ca(2+) stored in the
      endoplasmic reticulum and Ca(2+) influx from extracellular medium. However,
      pretreatment with BAPTA/AM, a Ca(2+) chelator, to prevent paroxetine-induced
      [Ca(2+)](i) increases did not protect cells from death. The results suggest that
      in MG63 cells, paroxetine caused Ca(2+)-independent apoptosis via inducing p38
      MAPK-associated caspase-3 activation.

PMID- 17174999
TI  - Study of the efficacy of the black stone on envenomation by snake bite in the
      murine model.
AB  - The black stone (BS) has been used since antiquity to treat envenomations. Since
      no actual clinical trial has ever been performed we used an experimental approach
      to evaluate its efficacy against the venoms of Bitis arietans, Echis ocellatus
      and Naja nigricollis. Local application of BS after intramuscular venom injection
      had no demonstrable effect on the outcome of envenomationa and it did not change
      the LD(50) of B. arietans venom. Our results show that, contrary to widespread
      belief, no efficacy to treat envenomation may be expected of the BS.

PMID- 17174997
TI  - p53-Dependent but ATM-independent inhibition of DNA synthesis and G2 arrest in
      cadmium-treated human fibroblasts.
AB  - This study focused on the activation of cell cycle checkpoint responses in
      diploid human fibroblasts that were treated with cadmium chloride and the
      potential roles of ATM and p53 signaling pathways in cadmium-induced responses.
      The alkaline comet assay indicated that cadmium caused a dose-dependent increase
      in DNA damage. Cells that were rendered p53-defective by expression of a dominant
      negative p53 allele or knockdown of p53 mRNA were more resistant to cadmium
      induced inactivation of colony formation than normal and ataxia telangiectasia
      (AT) cells. Synchronized fibroblasts in S were more sensitive to cadmium toxicity
      than cells in G1, suggesting that cadmium may target some element of DNA
      replication. Cadmium produced a dose- and time-dependent inhibition of DNA
      synthesis. An immediate inhibition was associated with severe delay in
      progression through S phase and a delayed inhibition seen 24 h after treatment
      was associated with accumulation of cells in G2. AT and normal cells displayed
      similar patterns of inhibition of DNA synthesis and G2 delay after treatment with
      cadmium, while p53-defective cells displayed significantly less of the delayed
      inhibition of DNA synthesis and accumulation in G2 post-treatment. Total p53
      protein and ser15-phosphorylated p53 were induced by cadmium in normal and AT
      cells. The p53 transactivation target Gadd45alpha was induced in both p53
      effective and p53-defective cells after 4 h cadmium treatment, and this was
      associated with an acute inhibition of mitosis. Cadmium produced a very unusual
      pattern of toxicity in human fibroblasts, inhibiting DNA replication and inducing
      p53-dependent growth arrest but without induction of p21(Cip1/Waf1) or activation
      of Chk1.

PMID- 17175000
TI  - Absence of biological damage from prolonged exposure to intravascular ultrasound:
      a swine model.
AB  - Ultrasound (US) has been used in IMS II (intravascular US) and CLOTBUST
      (transcranial US) clinical trials for thrombolysis. During the treatment, in
      addition to the targeted thrombus, other biological components, such as blood and
      vessel walls are subjected to long durations of US exposure. In this study we
      explored evidence of biological damage due to mechanical forces or thermal
      effects of US exposure at the frequency, intensity and duration employed for
      thrombolysis treatment. Biological effects were investigated by exposing swine
      ilio-femoral arteries bilaterally to an intravascular US generating catheter and
      a conventional catheter. A total of 12 animals each underwent 8h of exposure to
      intravascular pulsed US with a frequency of 2.2MHz and spatial peak time average
      intensity (I(SPTA)) of 6W/cm(2) per transducer (a total of six transducers per
      catheter) while the ultrasonic device surface temperature was maintained at 43
      degrees C. The animals were euthanized either 24+/-3h or 28+/-3 days post
      treatment. A range of physiological and hematological parameters were evaluated
      pre-, post-, and during US exposure. The vascular diameter was determined pre-
      and post-US exposure using angiograms. Following euthanasia, each animal
      underwent a gross pathological examination, and the treated vessels and an
      unexposed vessel were excised for comparative histopathological evaluation. No
      evidence of biological damage was found at the end of 8h exposure to
      intravascular US.

PMID- 17175001
TI  - Hepatitis C virus infects T cells and affects interferon-gamma signaling in T
      cell lines.
AB  - It has been reported that hepatitis C virus (HCV) may infect and replicate in
      human T cells, particularly in perihepatic lymph nodes, but the extent and
      consequence of T-cell infection in patients is unclear. This study is conducted
      to characterize the parameters and functional consequences of HCV infection in T
      lymphocytes. By using a lymphotropic HCV strain, we showed that HCV could infect
      T cell lines (Molt-4 and Jurkat cells) in vitro. Both positive- and negative
      strand HCV RNA were detected for several weeks after infection. Viral proteins
      could also be detected by immunofluorescence studies. Moreover, infectious HCV
      particles were produced from Molt-4 cell cultures, and could be used to infect
      naive T cell lines. HCV could also infect human primary CD4+ T cells,
      particularly naive (CD45RA+CD45RO-) CD4+ cells, in culture. The amounts of STAT-1
      and phosphorylated STAT-1 proteins in the infected Molt-4 cells were
      significantly less than those in uninfected cultures, suggesting the possibility
      of defect in interferon-gamma signaling. Indeed, T-bet and STAT-1 mRNA levels
      after interferon-gamma stimulation in infected Molt-4 were suppressed. In
      conclusion, HCV could infect and transiently replicate in T cells and that HCV
      replication suppressed the IFN-gamma/STAT-1/T-bet signaling due to the reduction
      of STAT-1 and inhibition of its activation (phosphorylation).

PMID- 17175002
TI  - Exploring the contribution of distal P4 promoter elements to the oncoselectivity
      of Minute Virus of Mice.
AB  - Minute Virus of Mice (MVM) shares inherent oncotropic properties with other
      members of the genus Parvovirus. Two elements responsible, at least in part, for
      this oncoselectivity have been mapped to an Ets1 binding site adjacent to the P4
      TATA box of the initiating promoter, P4, and to a more distal cyclic AMP
      responsive element (CRE), located within the telomeric hairpin stem. Here the CRE
      overlaps one half-site for the binding of parvoviral initiation factor (PIF),
      which is essential for viral DNA replication. We used a degenerate
      oligonucleotide selection approach to show that CRE binding protein (CREB)
      selects the sequence ACGTCAC within this context, rather than its more generally
      accepted palindromic TGACGTCA recognition site. We have developed strategies for
      manipulating these sequences directly within the left-end palindrome of the MVM
      infectious clone and used them to clone mutants whose CRE either matches the
      symmetric consensus sequence or is scrambled, or in which the PIF binding site is
      incrementally weakened with respect to the CRE. The panel of mutants were tested
      for fitness relative to wildtype in normal murine fibroblasts A9 or transformed
      human fibroblasts 324 K, through multiple rounds of growth in co-infected
      cultures, using a differential real-time quantitative PCR assay. We confirmed
      that inactivating the CRE substantially abrogates oncoselectivity, but found that
      improving its fit to the palindromic consensus is somewhat debilitating in either
      cell type. We also confirmed that reducing the PIF half-site spacing by one
      basepair enhances oncoselectivity, but found that a further basepair deletion
      significantly reduces this effect.

PMID- 17175004
TI  - The SSV1 viral integrase is not essential.
AB  - Viral integration is a widely conserved characteristic in viruses in all domains
      of life; however, its necessity is not well understood in many cases. Integration
      using tyrosine recombinases is one of the most widespread and best characterized
      mechanisms of integration. We completely removed the tyrosine recombinase
      integrase from the hyperthermophilic and acidophilic archaeal virus SSV1 using a
      novel LIPCR technique and found that the virus still replicated and spread in its
      host Sulfolobus solfataricus without integration. The mutant virus maintained a
      persistent infection but the integrase-lacking virus was less competitive than
      the wild-type virus when co-cultured. Based on these results, we discuss the
      necessity of integration and the possible advantages of this type of replication
      strategy.

PMID- 17175005
TI  - Distribution of PAHs and PCBs to dissolved organic matter: high distribution
      coefficients with consequences for environmental fate modeling.
AB  - Dissolved organic carbon/water distribution coefficients (K(DOC)) were measured
      for a selection of PCBs with octanol/water partition coefficients (K(OW)) ranging
      from 10(5.6) to 10(7.5). A solid phase dosing and sampling technique was applied
      to determine K(DOC) to Aldrich humic acid. This technique is in particular
      suitable for determining the distribution of very hydrophobic chemicals to
      complex matrices like humic acids. The K(DOC) values were calculated from the
      experimental data using a linear model. Determined K(DOC)'s were evaluated in
      relation to octanol/water partition coefficients of the test compounds, and
      compared to literature data. Measured K(DOC) values were somewhat higher than
      literature data, which can probably be attributed to the overestimation of freely
      dissolved aqueous concentration as a result of incomplete phase separation in
      other studies, and to the unique character of Aldrich humic acid as a "sorbent"
      or co-solute or to the fact that Aldrich humic acid is not a typical DOC, and
      other (adsorption) processes can occur. This study reports DOC distribution
      coefficients that belong to the highest ones ever measured. In addition, the DOC
      distribution was discussed in relation to current risk assessment modeling.

PMID- 17175003
TI  - High-throughput detection of human papillomavirus-18 L1 gene methylation, a
      candidate biomarker for the progression of cervical neoplasia.
AB  - The L1 gene of human papillomavirus-18 (HPV-18) is consistently hypermethylated
      in cervical carcinomas, but frequently hypo- or unmethylated in exfoliated cells
      from asymptomatic patients. In precancerous lesions, L1 is sporadically
      hypermethylated, correlating with the severity of the neoplasia. In order to
      explore the potential of using L1 methylation as a workable biomarker for
      carcinogenic progression of HPV-18 infections in routinely taken samples, our aim
      was to develop methylation-detection techniques that were sensitive and rapid
      without being overly complex technically. Therein, we developed a methylation
      specific PCR (MSP) through the design of primer sets that specifically amplify
      either methylated or unmethylated HPV-18 L1 DNA within bisulfite-modified sample
      DNA. Amplification of unmethylated and in vitro methylated HPV-18 DNA by MSP
      resulted in 2500 copies of either of the two L1 DNA species being detected, a
      satisfactory sensitivity considering that bisulfite treatment leads to the
      fragmentation of about 99% of sample DNA. The primers proved specific and did not
      generate false positive results at concentrations exceeding the lowest limit of
      detection by a factor of 400. DNA from carcinomas yielded PCR signals only with
      the methylation-specific primers, and not with primers specific for unmethylated
      L1 genes. The inverse result was obtained with DNA from precursor lesions that
      contained only hypomethylated DNA. High-grade precursor lesions and carcinomas
      that contained hyper- as well as hypomethylated L1 DNA yielded PCR signals with
      both primers. By developing a fluorescence based real-time PCR, we quantitatively
      analyzed samples with in vitro methylated and unmethylated L1 DNA, and could
      distinguish clinical samples with hyper- and hypomethylated DNA or mixtures of
      both DNAs. The methylation-specific and real-time PCR techniques permitted
      efficient HPV-18 L1 methylation analyses and open the door for larger-scale
      clinical studies where the utility of methylation status to predict the
      progression of HPV-18 infection and HPV-18 associated lesions is assessed.

PMID- 17175006
TI  - Diel mercury-concentration variations in streams affected by mining and
      geothermal discharge.
AB  - Diel variations of concentrations of unfiltered and filtered total Hg and
      filtered methyl Hg were documented during 24-h sampling episodes in water from
      Silver Creek, which drains a historical gold-mining district near Helena,
      Montana, and the Madison River, which drains the geothermal system of Yellowstone
      National Park. The concentrations of filtered methyl Hg had relatively large diel
      variations (increases of 68 and 93% from morning minima) in both streams.
      Unfiltered and filtered (0.1-microm filtration) total Hg in Silver Creek had diel
      concentration increases of 24% and 7%, respectively. In the Madison River,
      concentrations of unfiltered and filtered total Hg did not change during the
      sampling period. The concentration variation of unfiltered total Hg in Silver
      Creek followed the diel variation in suspended-particle concentration. The
      concentration variation of filtered total and methyl Hg followed the solar
      photocycle, with highest concentrations during the early afternoon and evening
      and lowest concentrations during the morning. None of the diel Hg variations
      correlated with diel variation in streamflow or major ion concentrations. The
      diel variation in filtered total Hg could have been produced by adsorption
      desorption of Hg2+ or by reduction of Hg(II) to Hg0 and subsequent evasion of
      Hg0. The diel variation in filtered methyl Hg could have been produced by
      sunlight- and temperature-dependent methylation. This study is the first to
      examine diel Hg cycling in streams, and its results reinforce previous
      conclusions that diel trace-element cycling in streams is widespread but often
      not recognized and that parts of the biogeochemical Hg cycle respond quickly to
      the daily photocycle.

PMID- 17175007
TI  - Spatiotemporal relationship between particle air pollution and respiratory
      emergency hospital admissions in Brisbane, Australia.
AB  - The nature of spatial variation in the relationship between air pollution and
      health outcomes within a city remains an open and important question. This study
      investigated the spatial variability of particle matter air pollution and its
      association with respiratory emergency hospital admissions across six geographic
      areas in Brisbane, Australia. Data on particles of 10 microm or less in
      aerodynamic diameter per cubic metre (PM10), meteorological conditions, and daily
      respiratory emergency hospital admissions were obtained for the period of 1
      January 1998 to 31 December 2001. A Poisson generalised linear model was used to
      estimate the specific effects of PM10 on respiratory emergency hospital
      admissions for each geographic area. A pooled effect of PM10 was then estimated
      using a meta-analysis approach for the whole city. The results of this study
      indicate that the magnitude of the association between particulate matter and
      respiratory emergency hospital admissions varied across different geographic
      areas in Brisbane. This relationship appeared to be stronger in areas with heavy
      traffic. We found an overall increase of 4.0% (95% confidence interval [CI]: 1.1
      6.9%) in respiratory emergency hospital admissions associated with an increase of
      10 microg /m3 in PM10 in the single pollutant model. The association was weaker
      but still statistically significant (an increase of 2.6%; 95% CI: 1.0-5.5%) after
      adjusting for O3, but did not appear to be affected by NO2. The effect estimates
      of PM10 were generally consistent for three spatial methods used in this study,
      but appeared to be underestimated if the spatial nature of the data was ignored.
      Therefore, the spatial variation in the relationship between PM10 and health
      outcomes needs to be considered when the health impact of air pollution is
      assessed, particularly for big cities.

PMID- 17175008
TI  - REE characteristics and Pb, Sr and Nd isotopic compositions of steel plant
      emissions.
AB  - A comprehensive Pb-Sr-Nd isotope and REE tracer study of atmospheric trace metal
      pollution by a steel plant situated to the north of the urban communities of
      Strasbourg (France) and Kehl (Germany) has been performed using tree barks as
      biomonitors. The 206Pb/207Pb and 208Pb/207Pb isotopic ratios of the steel plant's
      filter dust are similar to values found in dust of waste incinerators. The
      87Sr/86Sr ratio is similar to present-day ratios of Phanerozoic or Precambrian
      granitic rocks. The 143Nd/144Nd isotopic composition is very low and corresponds
      to an (Nd) value of -17.5. Such a low value is characteristic of old Precambrian
      granitic rocks and banded iron formations. Thus, this low (Nd) value might point
      to the origin of the iron necessary for the steel production. The fact, that this
      isotopic composition does not occur in crustal rocks of Western Central Europe
      makes the Nd isotope ratio a powerful tool to trace steel plants atmospheric
      emissions. The rare earth element (REE) distribution pattern of the steel plant's
      filter dust shows very specific fractionations like La and Nd enrichments which
      are traceable in tree barks over a distance of 4 km. The Pb, Sr and Nd isotope
      ratios not only enable the steel plant's emissions to be traced in a north
      easterly direction, along the principal wind pathway but also enables the
      interference of this emission at 4 km NE from the steel plant with another
      atmospheric component originating from the Strasbourg Rhine harbour to be
      identified.

PMID- 17175009
TI  - Case-control study of toenail cadmium and prostate cancer risk in Italy.
AB  - A role of cadmium exposure in prostate cancer etiology has been suggested by
      epidemiologic and laboratory studies, but conclusive evidence on this topic is
      still lacking. We investigated the relation between cadmium exposure, estimated
      by determining toenails cadmium levels, and prostate cancer risk in forty
      patients newly diagnosed with prostate cancer and fifty-eight hospital controls
      recruited in two provinces from southern and northern Italy. We found an excess
      cancer risk in subjects in the third and fourth (highest) quartiles of toenail
      cadmium concentration (odds ratio 1.3 and 4.7, respectively) compared with
      subjects in the bottom quartile. Results were basically unchanged when limiting
      the analysis to each province or entering toenail cadmium concentrations as
      continuous values in the regression model (P=0.004). Despite the limited
      statistical stability of the point estimates, these findings appear to support
      the hypothesis that cadmium exposure increases prostate cancer risk.

PMID- 17175010
TI  - Performance evaluation of a new rapid quantitative assay system for measurement
      of D-dimer in plasma and whole blood: PATHFAST D-dimer.
AB  - D-dimer is an indicator for in vivo fibrin formation, reflecting the formation of
      fibrin crosslinked by factor XIIIa. D-dimer assays are frequently used in
      emergency situations, such as diagnosis of venous thrombosis and pulmonary
      embolism, or disseminated intravascular coagulation. In these conditions, short
      sample turnaround times are essential. The PATHFAST D-dimer assay allows rapid
      quantitative measurement of D-dimer in plasma and whole blood. The study shows an
      excellent correlation between whole blood and plasma measurement of D-dimer both
      in the high range, as well as in the normal range. Intra-assay and inter-assay
      coefficients of variation (CV) were below 10%. The upper limit of normal (ULN =
      mean value measured in 100 samples from healthy blood donors + 2 x S.D.) was
      approximately 1 microg/ml FEU, using the assay-specific calibration. The maximal
      value measured in 20 replicates of calibrator 1 containing no D-dimer antigen was
      0.00052 microg/ml FEU, and this 10-fold lower than the declared detection limit
      of 0.005 microg/ml FEU. In conclusion, the PATHFAST D-dimer assay is the first
      automated fully quantitative D-dimer assay, which can use plasma and whole blood
      as sample materials in parallel.

PMID- 17175011
TI  - Non-NMDA receptors in frog retina: an immunocytochemical study.
AB  - Glutamate is one of the main neurotransmitters in the retina. Its effects are
      mediated by a large number of ionotropic and metabotropic membrane receptors. The
      distribution of ionotropic AMPA receptor subunits GluR1-4, kainate receptor
      subunits GluR5-7 and KA2, delta receptors 1-2, as well as the metabotropic
      receptor mGluR6 were studied in the frog retina. Indirect immunofluorescence was
      used to localize the different receptor subunits. Results showed that all
      subunits, with the exception of GluR1 and GluR5, are widely distributed in the
      retina. They are mainly located in both plexiform layers: the outer (OPL) and the
      inner one (IPL), where punctate labelling, a sign of synaptic localization, is
      observed. The metabotropic receptor mGluR6 is localised only in the OPL. The AMPA
      receptor subunit GluR4 is localised on the glial Muller cells of the retina. The
      vast majority of the subunits possess specific patterns of labelling that
      indicate that they are involved with different retinal functions. The
      significance of the AMPA receptors and involvement of glia in modulation of
      synaptic transmission are discussed.

PMID- 17175012
TI  - Uterine carcinosarcoma: immunohistochemical studies on tissue microarrays with
      focus on potential therapeutic targets.
AB  - OBJECTIVE: Carcinosarcoma of the uterus is a highly aggressive tumor containing
      both malignant epithelial and spindle (mesenchymal) components. Because of their
      rarity and poor clinical outcome, investigations into the expression of potential
      therapeutic targets are limited. The aim of this study was to determine the
      expression of therapeutic targets in both the epithelial and spindle
      (mesenchymal) components in 30 carcinosarcomas using tissue microarrays, for
      potential treatment strategy. METHODS: We collected formalin-fixed, paraffin
      embedded tissue blocks of carcinosarcoma of the uterine corpus resected from 30
      patients who had undergone total abdominal hysterectomies at our institution
      between 1985 and 2005 (ages 38-83 years, mean 65.9 years). All hematoxylin-eosin
      stained sections from each tumor were reviewed to confirm the pathologic
      diagnosis. Two tissue cores from the paraffin-embedded tissue blocks were
      constructed into a tissue microarray. Sections were stained with monoclonal
      antibodies against HER-2, VEGF, c-KIT, COX-2, and EGFR. Unequivocal staining of
      at least 5% tumor cells was considered positive. HER-2 amplification was also
      examined by fluorescence in situ hybridization (FISH) in 2 cases. RESULTS: In the
      epithelial component, expression of HER-2, VEGF, c-KIT, COX-2, and EGFR were
      detected in 2 (6%), 30 (100%), 0 (0%), 21 (70%), and 9 (30%) cases, respectively,
      whereas these expressions in the spindle (mesenchymal) component were detected in
      0 (0%), 28 (93%), 0 (0%), 5 (16%), and 20 (67%) cases, respectively. By FISH, one
      of the two cases with HER-2 expression showed gene amplification (2.62).
      CONCLUSIONS: VEGF is strongly expressed in both the epithelial and spindle
      (mesenchymal) components of uterine carcinosarcoma. This result warrants further
      study to evaluate the possible role of anti-angiogenic agents in cancer therapy
      for patients with uterine carcinosarcomas. The expression patterns of COX-2 and
      EGFR differed between the epithelial and spindle (mesenchymal) components. HER-2
      and c-KIT are poor therapeutic targets for uterine carcinosarcomas.

PMID- 17175013
TI  - Splenectomy in patients with advanced or recurrent ovarian cancer: open and
      laparoscopic surgical techniques and clinical outcomes.

PMID- 17175014
TI  - Beta-adrenergic-mediated inhibition of feeding by mercaptoacetate in food
      deprived rats.
AB  - This study investigated the effect of intraperitoneal (IP) injections of the
      fatty acid oxidation (FAO) inhibitor mercaptoacetate (MA, 45.6 mg/kg) on feeding
      in food-deprived rats. As previously, MA significantly stimulated feeding in ad
      libitum-fed rats. MA, however, reduced feeding in 18 and 36 h-fasted rats despite
      apparently antagonizing the fasting-induced increase in hepatic FAO. To test
      whether this anorectic effect involves beta-adrenergic stimulation, 36 h-fasted
      rats were IP injected with the nonspecific beta-adrenergic receptor antagonist
      propranolol (PROP, 0.5 mg/kg) just before MA injection. PROP attenuated MA's
      feeding-inhibitory effect, suggesting that MA anorexia is at least partially
      mediated by beta-adrenergic stimulation. Finally, we evaluated the role of
      subdiaphragmatic vagal afferent fibers in MA's feeding-inhibitory effect by
      testing the ability of MA to inhibit food intake in fasted rats after
      subdiaphragmatic vagal deafferentation (SDA). MA inhibited feeding similarly in
      SDA rats and sham-operated rats. These data demonstrate that subdiaphragmatic
      vagal afferents are not necessary for the feeding-inhibitory effect of peripheral
      MA. These results suggest that the FAO inhibitor MA elicits a feeding-inhibitory
      effect in fasted rats that is mediated by a different mechanism than its feeding
      stimulatory effect.

PMID- 17175016
TI  - Views on smoking cessation methods in ethnic minority communities: a qualitative
      investigation.
AB  - OBJECTIVE: The purpose of this qualitative analysis is to increase our
      understanding of minority smokers' experiences and beliefs about guideline
      recommended smoking cessation treatments. METHODS: We conducted sixteen focus
      groups (N=95) among current and former smokers from four ethnic minority
      communities in Minneapolis/St. Paul in 2005. Focus groups were conducted
      separately for American Indians, Vietnamese, Hmong and African Americans.
      RESULTS: Participants reported little experience with counseling and views on
      seeking help from physicians were mixed. African American and American Indian
      participants expressed feelings of mistrust and negative experiences with
      doctors. Hmong and Vietnamese smokers viewed doctors positively but did not
      regard them as an important resource to help with quitting, and especially for
      Vietnamese, the cultural value of mental control and self-determination was seen
      as most important to quit smoking. Across all the groups, pharmacotherapy was
      rarely utilized and participants had low knowledge and poor understanding of the
      benefits of pharmacotherapy. CONCLUSIONS: Personal beliefs, views toward doctors,
      and lack of knowledge are important determinants of the use of tobacco treatments
      among ethnic minority smokers. In order to increase minority smokers' utilization
      of evidence-based tobacco cessation treatments, effective strategies are needed
      to deliver accurate information about treatment from trusted sources.

PMID- 17175015
TI  - Associations of the dopamine D4 receptor gene VNTR polymorphism with drug use in
      adolescent psychiatric inpatients.
AB  - BACKGROUND: The VNTR polymorphism in the Dopamine D4 receptor gene (DRD4) has
      been associated with differential urge for substances across multiple
      methodologies ranging from neuroimaging to assessment in the natural environment.
      It is unclear whether the DRD4 gene is a marker for an underlying propensity for
      greater urge or whether the DRD4 gene differentially moderates the neuroadaptive
      effects of extended substance use on urge. Examination of the DRD4 in an
      adolescent sample may provide evidence of a mechanism of this putative
      relationship. METHOD: Data from a subset of 77 participants in a larger
      assessment study characterized adolescents for substance-related behaviors by
      DRD4 genotype. The psychiatrically admitted adolescents were genotyped for the
      variable number of tandem repeats polymorphism in the DRD4 gene (L>or=7 [n=25],
      S=or<7 [n=52]). Associations of the DRD4 with scores on the SASSI, and ADI were
      examined as well as selected individual items thought to be most related to the
      intermediate phenotype of urge. RESULTS: The DRD4 gene was not associated with
      any DSM-IV substance misuse diagnostic classification. Individual items related
      to urge were also nonsignificantly related to DRD4 status. Carriers of the long
      variant of the DRD4 polymorphism were more likely to have used hard drugs within
      the previous 6 months and scored higher on the self-medication subscale of the
      ADI compared to short variant homozygotes. DISCUSSION: Preliminary results
      provide little evidence for the DRD4 VNTR polymorphism to be related to urge
      related phenomena in hospitalized adolescents on a psychiatric inpatient unit.
      The association of the DRD4 gene with hard drug use may support literature
      linking this gene to impulsivity. Subscale findings may suggest a role of
      negative affect in previous DRD4 urge findings.

PMID- 17175017
TI  - Effect of macromolecules in solutions for vitrification of mature bovine oocytes.
AB  - This study was designed to evaluate vitrification procedures for in vitro matured
      bovine oocytes for efficient blastocyst production after warming, IVF and
      culture. A second goal was to replace serum as the macromolecular component of
      the vitrification solution, without compromising efficacy. The first experiment
      compared two containers, open pulled straws (OPS) versus cryoloops, and two
      vitrification protocols: short equilibration (H-TCM-199+10% EG+10% DMSO+20% FCS
      for 30s, followed by H-TCM-199+20% EG+20% DMSO+20% FCS+0.48M galactose for 20s)
      versus long equilibration (H-TCM-199+3% EG+20% FCS for 10min, followed by H-TCM
      199+31% EG+20% FCS+1M galactose for 20s). Subsequent experiments used only
      cryoloops and the short equilibration protocol to evaluate the effect of
      replacing FCS with defined macromolecules (BSA, Ficoll, PVP, and PVA) in
      vitrification solutions. Cryoloops were superior to OPS for vitrification of
      oocytes as determined by blastocyst production (P<0.05). The short and long
      vitrification protocols gave similar results. The presence of macromolecules in
      vitrification solutions for bovine oocytes was necessary for acceptable post
      warming developmental capacity; 20% FCS, 1% and 2% BSA, 6% and 18% Ficoll, 6% and
      20% PVP, 1% PVA, and the combinations of 18% Ficoll+1% BSA, and 6% PVP+1% BSA
      provided similar protection during vitrification of oocytes; development ranged
      from 14.8% to 23.0% blastocysts/oocyte, which was not different (P>0.05) from non
      vitrified controls (26.9-34.0% blastocysts/oocyte). Too much (6%) and too little
      (0.3%) BSA, and 0.3% PVA for vitrification resulted in lower blastocyst
      production (P<0.05) relative to unvitrified oocytes.

PMID- 17175018
TI  - Nutrient dynamics at the sediment-water interface in a Mediterranean lagoon
      (Thau, France): influence of biodeposition by shellfish farming activities.
AB  - The Thau Lagoon, a French Mediterranean shallow lagoon, is a site where extensive
      shellfish farming occurs. The aim of the present work is to evaluate the role of
      this activity on nutrient exchange at the sediment-water interface in relation to
      organic matter (OM) sedimentation and degradation. Two stations inside (C5) and
      outside (C4) of the shellfish farming areas were sampled at three seasons.
      Porewater chemistry surveys and calculated diffusive fluxes were used to evaluate
      the trophic status of the Thau lagoon. Quantitative (Particulate Organic Carbon)
      as well as qualitative OM (Hydrogen Index, Carbohydrates) analyses were performed
      on sediments to assess OM characteristics. Results emphasized that surficial
      sediments at C5 are always more enriched in OM. Porewater nutrient concentrations
      are 10-20 times higher at C5 than at C4. In June 2003, the porewater profiles
      exhibit a sharp gradient at the bottom waters, indicating a hypereutrophic
      status, leading to an anoxic crisis.

PMID- 17175019
TI  - Short-term response of the slow growing seagrass Posidonia oceanica to simulated
      anchor impact.
AB  - Experimental evaluations about the impact of anchors of small vessels have
      previously shown that each anchoring can on average damage up to six shoots of
      Posidonia oceanica, removing small amount of biomass and, at the same time,
      interrupting continuity among shoots. The aim of the paper was to investigate the
      response of P. oceanica to different damage intensity at two levels of substrata
      compactness. Three treatments were considered: control (no damage); low damage
      (simulated anchor damage by three strokes of a hoe); and high damage (six
      strokes). Disturbance was higher where the substratum was highly penetrable and
      after one year significant variation was observed among treatments for both the
      number of leaves per shoot and shoot density. Conversely, the number of leaves
      per shoot by the end of the study was similar among all treatment combinations,
      suggesting that this was the only phenological feature that recovered, and
      probably the only result that through clonal integration could be achieved. These
      data strongly highlighted the role that anchoring might have on the slow growing
      seagrass P. oceanica meadow.

PMID- 17175020
TI  - Effects of growth condition on the structure of glycogen produced in
      cyanobacterium Synechocystis sp. PCC6803.
AB  - Growth and glycogen production were characterized for Synechocystis sp. strain
      PCC6803 grown under continuous fluorescent light in four variations of BG-11
      medium: either with (G+) or without (G-) 5mM glucose, and with a normal (N+, 1.5
      g sodium nitrate/L) or a reduced (N-, 0.084 g sodium nitrate/L) nitrogen
      concentration. Glucose-supplemented BG-11 with a normal nitrogen concentration
      (N+G+) produced the highest growth rate and the greatest cell density. Although
      the maximum cell mass production was observed in the N+G+ medium, the highest
      glycogen yield (19.0mg/g wet cell mass) was achieved under the glucose
      supplemented, nitrogen-limiting condition (N-G+). The addition of glucose
      enhanced cell growth, while nitrogen limitation apparently directed carbon flux
      into glycogen accumulation rather than cell growth. Transmission electron
      microscopic analysis showed that, under nitrogen-limiting conditions (N-G+),
      glycogen particles accumulated in large amounts and filled the cytosol of the
      cells. Analysis by high-performance size-exclusion chromatography further
      revealed that the glycogen produced in N-G+ medium had the longest average branch
      chain-length (DP10.4) among the conditions tested. When the yield and structure
      of glycogen were examined in different growth phases, the greatest yield (36.6
      mg/g wet cell mass) and the longest branch chain-length (DP10.7) were observed 2
      days after the fully grown cells in the N+G+ medium were transferred to the
      growth restricting (N-G+) medium.

PMID- 17175022
TI  - Extracellular matrix formation and mineralization on a phosphate-free porous
      bioactive glass scaffold using primary human osteoblast (HOB) cells.
AB  - Sol-gel derived bioactive glasses of the 70S30C (70mol% SiO2, 30mol% CaO)
      composition have been foamed to produce 3D bioactive scaffolds with hierarchical
      interconnected pore morphologies similar to trabecular bone. The aim of this
      study was to investigate primary human osteoblast response to porous bioactive
      glass scaffolds. The scaffolds supported osteoblast growth and induced
      differentiation, within the 3-week culture period, as depicted by enhanced ALPase
      enzymatic activity, without the addition of supplementary factors such as
      ascorbic acid, beta-glycerophosphate and dexamethasone. This is the first time
      this has been observed on a bioactive glass that does not contain phosphate.
      Deposition of extracellular matrix was also confirmed by enhanced production of
      the extracellular matrix protein collagen type I. SEM showed indications of
      mineralized bone nodule formation without the addition of growth factors. The
      70S30C bioactive glass scaffolds therefore fulfil many of the criteria for an
      ideal scaffold for bone tissue engineering applications.

PMID- 17175023
TI  - Subtypes of female juvenile offenders: a cluster analysis of the Millon
      Adolescent Clinical Inventory.
AB  - The current study sought to explore subtypes of adolescents within a sample of
      female juvenile offenders. Using the Millon Adolescent Clinical Inventory with
      101 female juvenile offenders, a two-step cluster analysis was performed
      beginning with a Ward's method hierarchical cluster analysis followed by a K
      Means iterative partitioning cluster analysis. The results suggest an optimal
      three-cluster solution, with cluster profiles leading to the following group
      labels: Externalizing Problems, Depressed/Interpersonally Ambivalent, and Anxious
      Prosocial. Analysis along the factors of age, race, offense typology and offense
      chronicity were conducted to further understand the nature of found clusters.
      Only the effect for race was significant with the Anxious Prosocial and Depressed
      Intepersonally Ambivalent clusters appearing disproportionately comprised of
      African American girls. To establish external validity, clusters were compared
      across scales of the Behavioral Assessment System for Children - Self Report of
      Personality, and corroborative distinctions between clusters were found here.

PMID- 17175021
TI  - FT-IR imaging of native and tissue-engineered bone and cartilage.
AB  - Fourier transform infrared (FT-IR) imaging and microspectroscopy have been
      extensively applied to the analyses of tissues in health and disease. Spatially
      resolved mid-IR data has provided insights into molecular changes that occur in
      diseases of connective or collagen-based tissues, including, osteoporosis,
      osteogenesis imperfecta, osteopetrosis and pathologic calcifications. These
      techniques have also been used to probe chemical changes associated with load,
      disuse, and micro-damage in bone, and with degradation and repair in cartilage.
      This review summarizes the applications of FT-IR microscopy and imaging for
      analyses of bone and cartilage in healthy and diseased tissues, and illustrates
      the application of these techniques for the characterization of tissue-engineered
      bone and cartilage.

PMID- 17175025
TI  - Comparative sediment quality assessment in different littoral ecosystems from
      Spain (Gulf of Cadiz) and Brazil (Santos and Sao Vicente estuarine system).
AB  - The goal of this work was to establish comparisons among environmental
      degradation in different areas from Southern Spain (Gulf of Cadiz) and Brazil
      (Santos and Sao Vicente estuary), by using principal component analyses (PCA) to
      integrate sediment toxicity (amphipods mortality) and chemical-physical data (Zn,
      Cd, Pb, Cu, Ni, Co, V, PCBs, PAHs concentrations, OC and fines contents). The
      results of PCA extraction of Spanish data showed that Bay of Cadiz, CA-1 did not
      present contamination or degradation; CA-2 exhibited contamination by PCBs,
      however it was not related to the amphipods mortality. Ria of Huelva was the most
      impacted site, showing contamination caused principally by hydrocarbons, in HV-1
      and HV-2, but heavy metals were also important contaminants at HV-1, HV-2 and HV
      3. Algeciras Bay was considered as not degraded in GR-3 and -4, but in GR-3' high
      contamination by PAHs was found. In the Brazilian area, the most degraded
      sediments were found in the stations situated at the inner parts of the estuary
      (SSV-2, SSV-3, and SSV-4), followed by SSV-6, which is close to the Submarine
      Sewage Outfall of Santos - SSOS. Sediments from SSV-1 and SSV-5 did not present
      chemical contamination, organic contamination or significant amphipod mortality.
      The results of this investigation showed that both countries present
      environmental degradation related to PAHs: in Spain, at Ria of Huelva and
      Gudarranque river's estuary areas; and in Brasil, in the internal portion of the
      Santos and Sao Vicente estuary. The same situation is found for heavy metals,
      since all of the identified metals are related to toxicity in the studied areas,
      with few exceptions (V for both Brazil and Spain, and Cd and Co for Brazilian
      areas). The contamination by PCBs is more serious for Santos and Sao Vicente
      estuary than for the investigated areas in Gulf of Cadiz, where such compound did
      not relate to the toxicity.

PMID- 17175024
TI  - Glutathione S-tranferases and cytochrome P450 activities in Mytilus
      galloprovincialis from the South coast of Portugal: effect of abiotic factors.
AB  - To assess the health of aquatic organisms, biomarkers that measure changes at the
      biochemical level have been used as effective early warning tools in ecological
      risk assessment. In order to develop an integrated risk assessment strategy for
      the south coast of Portugal, mussels Mytilus galloprovincialis were collected
      from six sites along the coast with different organic contaminant
      characteristics. Additionally, an active biomonitoring approach was followed by
      transplanting indigenous mussels from site 4 to 6 and vice versa (from site 6 to
      4) for 28 days. PAHs and PCBs contents were measured and the associated responses
      of phase I and phase II detoxification mechanisms evaluated by measuring
      cytochrome P450 and GST activities. GST activity was also determined on different
      tissues (gills, digestive gland, foot, mantle and gonads) of M. galloprovincialis
      and the impact of abiotic parameters (temperature, salinity, pH, conductivity and
      dissolved oxygen) on the GST activity assessed. Results indicate that CYP 450
      follow the same pattern of PAHs and a direct relationship exist between CYP 450
      and PAH levels from the different sites. Although there is a decrease between GST
      and PAHs concentrations it was not significant. The majority of the GST activity
      was in the gills and the digestive gland (around of 75% of the activity measured
      in all tissues) followed in decreasing order by the mantle, gonads. An inverse
      relationship between GST activity and salinity was detected along with
      temperature although not significant. These two biomarkers respond to changes of
      these two groups of compounds and to salinity especially for GST. In conclusion
      CYP 450 in mussels gives a reliable response as biomarker for organic
      contaminants in risk assessment in the South Coast of Portugal.

PMID- 17175026
TI  - Binding of the adhesion and pathogen receptor DC-SIGN by monocytes is regulated
      by the density of Lewis X molecules.
AB  - Soluble DC-SIGN (CD209) bind unsialylated Lewis X epitopes that are abundantly
      expressed on neutrophils. Due to the low expression of unsialylated Lewis X
      epitopes on monocytes, no binding of soluble DC-SIGN molecules was seen. In
      contrast, beads coated with multiple DC-SIGN molecules show a high percentage of
      binding to monocytes. The increased number of DC-SIGN molecules present on the
      beads enable multivalent interactions between the DC-SIGN molecules and the
      scarce Lewis X epitopes present on monocytes. Increased expression of
      unsialylated Lewis X epitopes on monocytes after neuraminidase treatment
      coincided with enhanced binding to soluble DC-SIGN. Multiple unsialylated Lewis X
      epitopes in close proximity of each other are now able to interact multivalently
      to soluble DC-SIGN. From these findings, we conclude that firm interactions
      between DC-SIGN and monocytes can be established by either increasing the density
      of DC-SIGN molecules at the cell surface or by increasing the number of Lewis X
      epitopes. Regulating the number of ligands endows monocytes with the capacity to
      modulate binding to DC-SIGN. This may result in a bi-directional cross-talk
      between DC and monocytes, to modulate innate and/or adaptive immune responses.

PMID- 17175028
TI  - Emerging invasive liver abscess caused by K1 serotype Klebsiella pneumoniae in
      Korea.
AB  - OBJECTIVES: The high incidence of invasive liver abscess caused by Klebsiella
      pneumoniae in Taiwan, contrasted with the rareness of this disease in Western
      countries, has aroused special interest. There have been few detailed reports
      from other Asian countries. To investigate a current epidemiology of K.
      pneumoniae liver abscess in Korea and to determine K serotype distribution in K.
      pneumoniae strains causing liver abscess, we performed a nationwide prospective
      study. METHODS: Community-acquired, culture-proven liver abscess cases were
      enrolled between 2004 and 2005. Etiologies and clinical features were analyzed.
      K. pneumoniae isolates were serotyped according to K antigen. Meta-analysis was
      done to determine the time trend of the etiologies of liver abscess in Korea.
      RESULTS: Out of 371 cases collected prospectively, 290 (78.2%) were caused by K.
      pneumoniae. Most K. pneumoniae liver abscesses were monomicrobial. Diabetes
      mellitus was the most common underlying disease (39.9%). Distant metastatic
      infections were frequently observed (8.7%). magA PCR revealed that 95 (59.4%) out
      of 160 K. pneumoniae isolates belonged to the K1 serotype. CONCLUSIONS: Our study
      indicates that K. pneumoniae has emerged as a major etiologic agent of liver
      abscess in Korea, and these emerging infections seem to be attributable to
      invasive K. pneumoniae strains with capsular K1 serotype.

PMID- 17175029
TI  - Current trends in solid-phase-based extraction techniques for the determination
      of pesticides in food and environment.
AB  - Solid-phase extraction (SPE) procedures for pesticide residues in food and
      environment are reviewed and discussed. The use of these procedures, which
      include several approaches such as: matrix solid-phase dispersion (MSPD), solid
      phase micro-extraction (SPME) and stir-bar sorptive extraction (SBSE), represents
      an opportunity to reduce analysis time, solvent consumption, and overall cost.
      SPE techniques differ from solvent extraction depending on the interactions
      between a sorbent and the pesticide. This interaction may be specific for a
      particular pesticide, as in the interaction with an immunosorbent, or non
      specific, as in the way a number of different pesticides are adsorbed on apolar
      or polar materials. A variety of applications were classified according to the
      method applied: conventional SPE, SPME, hollow-fiber micro-extraction (HFME),
      MSPD and SBSE. Emphasis is placed on the multiresidue analysis of liquid and
      solid samples.

PMID- 17175027
TI  - Gene expression profiling of human primary astrocytes exposed to manganese
      chloride indicates selective effects on several functions of the cells.
AB  - Exposure of adult humans to manganese (Mn) has long been known to cause
      neurotoxicity. Recent evidence also suggests that exposure of children to Mn is
      associated with developmental neurotoxicity. Astrocytes are critical for the
      proper functioning of the nervous system, and they play active roles in
      neurogenesis, synaptogenesis and synaptic neurotransmission. In this report, to
      help elucidate the molecular events underlying Mn neurotoxicity, we
      systematically identified the molecular targets of Mn in primary human astrocytes
      at a genome-wide level, by using microarray gene expression profiling and
      computational data analysis algorithms. We found that Mn altered the expression
      of diverse genes ranging from those encoding cytokines and transporters to signal
      transducers and transcriptional regulators. Particularly, 28 genes encoding
      proinflammatory chemokines, cytokines and related functions were up-regulated,
      whereas 15 genes encoding functions involved in DNA replication and repair and
      cell cycle checkpoint control were down-regulated. Consistent with the increased
      expression of proinflammatory factors, analysis of common regulators revealed
      that 16 targets known to be positively affected by the interferon-gamma signaling
      pathway were up-regulated by Mn(2+). In addition, 68 genes were found to be
      similarly up- or down-regulated by both Mn(2+) and hypoxia. These results from
      genomic analysis are further supported by data from real-time RT-PCR, Western
      blotting, flow cytometric and toxicological analyses. Together, these analyses
      show that Mn(2+) selectively affects cell cycle progression, the expression of
      hypoxia-responsive genes, and the expression of proinflammatory factors in
      primary human astrocytes. These results provide important insights into the
      molecular mechanisms underlying Mn neurotoxicity.

PMID- 17175030
TI  - Porcine circovirus type 2 (PCV2) distribution and replication in tissues and
      immune cells in early infected pigs.
AB  - Replication of porcine circovirus type 2 (PCV2) in pigs, as measured by spliced
      capsid mRNA (Cap mRNA) and viral DNA, was investigated following experimental
      infection. Peripheral blood mononuclear cells (PBMCs), and tissue from bronchial
      lymph nodes (BLN), inguinal lymph nodes (ILN), tonsils, lungs, liver, kidneys,
      spleen and thymus from infected pigs on different days post-infection (DPI) were
      assessed. PCV2 replication differed dramatically between tissues from the same
      infected pig. The virus actively replicated in most tested tissues at 14DPI in
      association with increased PCV2 associated lesions and PCV2 antigen levels,
      although no clinical signs correlated with PCV2 associated disease were observed
      in infected pigs during the course of the study. The PCV2 Cap mRNA was detected
      only at 13DPI in PBMCs from infected pigs, suggesting replication of the virus in
      circulating blood is transient and not a major site for PCV2 replication in vivo.
      Evaluation of the Cap mRNA and viral DNA synthesis in T and B lymphocyte and
      monocyte populations from PBMCs and BLN at various intervals post-inoculation
      revealed replication of PCV2 in all cell subpopulations; however, viral
      replication in B lymphocytes was greater than observed in mononuclear cells
      isolated from BLN at 14DPI indicating that B lymphocytes may be an important cell
      population for PCV2 replication. These findings further our understanding of the
      cell types permissive for PCV2 replication and the pathogenesis of PCV2 infection
      in vivo.

PMID- 17175032
TI  - The neuropeptide genes TAC1, TAC3, TAC4, VIP and PACAP(ADCYAP1), and
      susceptibility to multiple sclerosis.
AB  - The related immunomodulatory neuropeptides vasoactive intestinal peptide (VIP)
      and pituitary adenylyl cyclase activating peptide (PACAP; gene symbol ADCYAP1)
      have recently been proposed as novel therapeutics for the treatment of multiple
      sclerosis (MS). These neuropeptides, as well as those belonging to the tachykinin
      family exert pleiotropic effects, many of which are of relevance to central
      nervous system inflammation. In the present study, we have analysed 14 single
      nucleotide polymorphisms (SNPs) and 4 microsatellite markers in the VIP, ADCYAP1,
      TAC3 and TAC4 genes for susceptibility to MS in a case-control collection from
      Northern Ireland. Following correction for multiple comparisons, we did not find
      any significant associations between single polymorphic markers or multiple
      marker haplotypes and susceptibility to MS. Furthermore, we analysed 2 SNPs in
      the TAC1 gene in a set of Sardinian trio MS families, based on our previous
      observation of association of these SNPs with MS in the Northern Irish (Genes
      Immun. 2005, 6, 265-270). Analysis of these SNPs in the Sardinians was not
      significant though a similar trend to that originally observed in the Northern
      Irish was present. Meta-analysis of the Sardinian and Northern Irish TAC1 SNP
      genotype data revealed a Mantel-Haenszel Common OR Estimate for the TAC1 intron 1
      SNP rs2072100 of 0.76 (95% CI 0.63-0.92; P=0.005; A allele) and for the TAC1
      promoter SNP rs7793277 of 0.76 (95% CI 0.615-0.95; P=0.014; C allele). Our data
      advocate a need for further exploration of the TAC1 gene region in MS.

PMID- 17175033
TI  - Parental awareness of hearing impairment in their school-going children and
      healthcare seeking behaviour in Kisumu district, Kenya.
AB  - BACKGROUND: Hearing-impaired children who are identified early and appropriately
      managed have improved outcomes in speech, language, cognitive and social
      development. Enhanced parental awareness of their child's hearing disability,
      behavioral, developmental and psychosocial limitations is essential to sustaining
      timely detection and appropriate intervention. Additionally, availability of
      services for diagnosis, treatment and habilitation would improve the demand for
      pedaudiological care in this community. OBJECTIVE: To describe level of parental
      awareness of childhood HI and the pattern of access to and utilization of
      ambulatory care services. SUBJECTS: Thirty-three parents of lower primary school
      going children who failed audiometric screening from sampled schools in Kisumu
      district, western Kenya. MAIN OUTCOME MEASURES: First person to detect HI, age of
      child at first suspicion of HI, source of ambulatory health care and use of the
      health care facilities. RESULTS: The prevalence of HI was 2.48%. Most
      parents/guardians (69.7%) were aware of their child's hearing impairment. Of
      these, 63.6% were first to detect HI in the pupils, while 30.3% were detected by
      screen. Most children (57.2%) were first recognized with (HI) after age 2 years.
      The mean age at identification was 5.5 years. The median travel distance to the
      preferred health care facility was 2 km (IQR 1-2.5). Parents seldom sought or
      lacked help for their hearing-impaired children. Of 27.3% who asked for hearing
      assessment, 9.1% received some counsel on HI and 12.1% received medication, one
      (3%) was referred for audiological assessment and none used a hearing aid. Use of
      health facilities for maternal care was (65.7%) and immunization (62.9%).
      CONCLUSIONS: Despite adequate parental awareness of chronic childhood disability,
      health facilities were underutilized. This indicates the need to further
      stimulate and maintain a desirable level of uptake of services for diagnosis,
      treatment and habilitation of childhood HI, while sustaining delivery of
      effective and acceptable high quality paediatric care.

PMID- 17175031
TI  - Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses
      of microglia and astrocytes.
AB  - Liver X receptors (LXRs) are nuclear receptors previously identified to be
      important in lipid metabolism. Recent reports suggest that LXR agonists also
      exhibit anti-inflammatory properties in mouse models of atherosclerosis and
      contact dermatitis. In the present study, we investigated the effects of LXR
      agonists on mouse microglia and astrocytes. When chronically activated, these
      resident-CNS glia have been implicated in the pathology of neuroinflammatory
      disorders including multiple sclerosis (MS). Our studies demonstrated for the
      first time that LXR agonists inhibited the production of nitric oxide, the pro
      inflammatory cytokines IL-1beta and IL-6 and the chemokine MCP-1 from LPS
      stimulated microglia and astrocytes. Furthermore, LXR agonists inhibited LPS
      induction of nuclear factor-kappa B (NF-kappaB) DNA-binding activity. These
      agonists also blocked LPS-induction of IkappaB-alpha protein degradation in
      microglia, suggesting a mechanism by which these agonists modulate NF-kappaB DNA
      binding activity. These studies suggest that LXR agonists suppress the production
      of pro-inflammatory molecules by CNS glia, at least in part, by modulating NF
      kappaB-signaling pathways. Retinoid X receptors (RXRs) physically interact with
      LXR receptors, and the resulting obligate heterodimer regulates the expression of
      LXR-responsive genes. Interestingly, a combination of LXR and RXR agonists
      additively suppressed the production of NO by microglia and astrocytes.
      Collectively, these studies suggest that LXR agonists may be effective in the
      treatment of neuroinflammatory diseases including MS.

PMID- 17175034
TI  - Monitoring HCV RNA viral load by locked nucleic acid molecular beacons real time
      PCR.
AB  - Locked nucleic acids (LNA) based real time PCR was used in particular situations
      where there are difficulties in primer design due to sequence complexity. In this
      study a new real time RT-PCR assay was developed using LNA modified primers and
      LNA molecular beacon probes to monitor hepatitis C virus (HCV) viral load in
      plasma and serum samples. The technique did not suffer from an heterogeneity of
      the HCV genome and, in addition, an internal RNA control was amplified in the
      same reaction tube with different short primers and beacon probe. Due to the
      short consensus LNA primers length, the PCR efficiency was close to 100% with no
      formation of hairpin loop structures. In summary a new LNA molecular beacon based
      real time RT-PCR assay was used successfully to measure quantitatively the total
      level of HCV RNA in both experimental and clinical specimens. The high
      sensitivity (50 IU/ml), the wide range of genotype detection, increased
      specificity and robustness obtained with this test are particularly useful for
      screening large number of specimens and measuring viral loads to monitor the
      progress of the disease.

PMID- 17175035
TI  - The helicase primase inhibitor, BAY 57-1293 shows potent therapeutic antiviral
      activity superior to famciclovir in BALB/c mice infected with herpes simplex
      virus type 1.
AB  - BAY 57-1293 represents a new class of potent inhibitors of herpes simplex virus
      (HSV) that target the virus helicase primase complex. The present study was
      conducted using the zosteriform infection model in BALB/c mice. The helicase
      primase inhibitor, BAY 57-1293 was shown to be highly efficacious in this model.
      The beneficial effects of therapy were obtained rapidly (within 2 days) although
      the onset of treatment was delayed for 1 day after virus inoculation. The
      compound given orally, or intraperitoneally once per day at a dose of 15 mg/kg
      for 4 successive days was equally effective or superior to a much higher dose of
      famciclovir (1mg/ml, i.e. approximately 140-200mg/kg/day) given in the drinking
      water for 7 consecutive days, which, in our hands, is the most effective method
      for administering famciclovir to mice. In contrast to the vehicle-treated
      infected mice, all mice that received antiviral therapy looked normal and active
      with no mortality, no detectable loss of weight and no marked change in ear
      thickness. BAY 57-1293 and famciclovir reduced the virus titers in the skin to
      below the level of detection by days 3 and 7 post infection, respectively. In
      both BAY 57-1293 and famciclovir-treated mice, infectious virus titers in the ear
      pinna and brainstem remained below the level of detection. Consistent with these
      findings, BAY 57-1293 also showed a potent antiviral effect in an experiment
      involving a small number of severely immunocompromised athymic-nude BALB/c mice.

PMID- 17175036
TI  - Anxiolytic-like effect of 5-HT(2) ligands and benzodiazepines co-administration:
      comparison of two animal models of anxiety (the four-plate test and the elevated
      plus maze).
AB  - Animal models of anxiety remain a useful tool for evaluating the anxiolytic-like
      effect of new treatments. Even though many tests are similarly based on
      exploration tasks, using more than one animal model is all the more recommended
      since there are qualitative differences between such tests. Furthermore, although
      many tests are excellent tool for detecting benzodiazepines/GABA compounds,
      inconsistent results have been reported for 5-HT ligands. Here, two animal models
      have been chosen, the elevated plus maze (EPM) based on the natural aversion of
      rodents for open spaces and the four-plates test (FPT) a models involving the
      animal's conditioned response to stressful events. In a recent study, we have
      demonstrated that the 5-HT(2A/2C) agonist DOI and the 5-HT(2B) agonist BW 723C86
      were shown to produce an anxiolytic-like effect in both tests. This study aimed
      to evaluate a putative interaction between benzodiazepine and 5-HT(2) ligands in
      the FPT and the EPM. Indeed, close distribution of GABA(A) and 5-HT(2) receptors
      was found in brain structures leading to functional interrelation. In the FPT,
      sub-active doses of alprazolam and diazepam were strongly potentiated by DOI. BW
      723C86, also potentiated the anxiolytic-like effect of the two benzodiazepines
      with a weaker effect. In the same way, DOI and benzodiazepines administration
      induced an increase in the anxiolytic-like parameters in the EPM with a strongest
      effect observed with alprazolam. Regardless of anxiety models used in this study,
      5-HT(2A) ligands exerted facilitatory influence upon GABAergic system. Therefore,
      the FPT and the EPM might implicate the same kind of anxiety.

PMID- 17175037
TI  - Orlistat reduces gallbladder emptying by inhibition of CCK release in response to
      a test meal.
AB  - BACKGROUND AND AIMS: Orlistat is a covalent inhibitor of digestive lipase derived
      from lipstatin, the natural product of Streptomyces toxytricini. By blocking the
      active site of intestinal lipase, orlistat inhibits hydrolysis of dietary
      triglycerides and thus reduces the intestinal lipid absorption. It is uncertain
      whether intestinal inhibition of lipase by orlistat also interferes with nutrient
      induced CCK release from intestinal I-cells. The aim of the present study was
      therefore to assess whether oral administration of orlistat inhibits CCK release
      in response to a test meal and thus causes impaired gallbladder emptying.
      METHODS: 22 healthy volunteers were given a test meal consisting of 200 ml dairy
      cream and two teaspoons of chocolate powder (552 kcal=2328 kJ; 56.0 g fat; 5.2 g
      proteins, 6.6 g carbohydrates), with and without oral application of 120 mg
      orlistat. Gallbladder volume was determined by ultrasound before and 5, 10, 20,
      30 and 40 min after meal ingestion. In parallel, a venous blood sample was
      collected for the measurement of bioactive CCK. CCK activity was assessed using a
      bioassay with isolated rat pancreatic acini cells. RESULTS: Oral administration
      of orlistat significantly impairs gallbladder emptying. After ingestion of the
      test meal the gallbladder contracted by 78.5% in the control group, whereas the
      test group with orlistat only showed a contraction of 45.7% (p<0.01). Maximal
      contraction was reached after 35 to 40 min, the maximal gallbladder emptying was
      delayed up to 10 min by orlistat. Orlistat induced a significant reduction of
      bioactive CCK levels in response to a test meal (CCK(max) with orlistat=4.1
      pmol/l; CCK(max) without orlistat=7.8 pmol/l). CCK levels were reduced by 47% and
      the onset of maximal CCK secretion was delayed up to 10 min. CONCLUSION: The
      inhibition of intestinal lipolytic activity by orlistat results in reduced
      gallbladder emptying through inhibition of meal-mediated CCK release. We
      therefore hypothesize that impaired gallbladder motility may represent a risk
      factor in chronic treatment of severe obesity using orlistat.

PMID- 17175038
TI  - Parallel inactivation of Y2 receptor and G-proteins in CHO cells by pertussis
      toxin.
AB  - The Y(2) receptor for neuropeptide Y (NPY) interacts with pertussis toxin (PTX)
      sensitive G-proteins, but little is known about interdependence of their levels
      and functions. We found that PTX reduces Y(2) receptors expressed in CHO cells in
      parallel to inactivation of Gi G-proteins, to loss of inhibition by Y(2) agonists
      of forskolin-stimulated adenylyl cyclase, and to decrease in the binding of GTP
      gamma-S. These losses were attenuated by the endosome alkalinizer ammonium
      chloride. Affinity of the Y(2) receptor was not changed by PTX treatment.
      Prolonged treatment induced a large decrease of Y(2) receptor immunoreactivity
      (more than 70% in 48 h). The Gi(3) alpha-subunit immunoreactivity decreased
      slowly (about 46% in 48 h). There was a significant increase in Gq alpha
      immunoreactivity and in fraction of Y(2) binding sensitive to a Gq-selective
      antagonist. Possibly linked to that, the surface Y(2) sites and the
      internalization of the Y(2) receptor were less than 40% reduced. However, the
      abundant masked Y(2) sites were eliminated by the toxin, and could be mainly
      coupled to PTX-sensitive G-proteins.

PMID- 17175039
TI  - Pharmacokinetics of 125I-GST-TatdMt, a recombinant fusion protein possessing
      potent anti-obesity activity, after intravenous, nasal, oral, and subcutaneous
      administration.
AB  - This study first reports the absorption kinetics of GST-TatdMt, a recombinant Tat
      protein possessing potent anti-obesity activity, in rats after nasal, s.c., and
      p.o. administration. GST-TatdMt was over-expressed in E. coli, purified, and
      radioiodinated using the IODO-GEN method. The radioiodinated 125I-GST-TatdMt was
      administered to rats by nasal, s.c., and oral routes at doses of 7.3 microg
      (420.7 nCi), 146.5 microg (8413.8 nCi), and 146.5 microg (8413.8 nCi),
      respectively. For the determination of absolute bioavailability, 125I-GST-TatdMt
      was also given to rats by i.v. injection (73.2 microg, 4206.9 nCi). Following
      administration by extravascular routes, the systemic absorption of radioactivity
      was prolonged, with Cmax being attained within 4.2-8.0 h. The absolute
      bioavailability calculated as dose-normalized AUC(extravascular)/AUC(i.v.) was
      98.0, 75.8, and 87.1% after nasal, s.c., and oral administration, respectively.
      The majority of administered radioactivity was excreted in urine (57.5-64.7%),
      with fecal excretion being less (2.5-12.7%). The distribution of 125I-GST-TatdMt
      to various tissues was also determined at 4 and 72 h after s.c. injection. The
      findings of this study suggest that this protein may be absorbed into the
      systemic circulation when given by extravascular administration.

PMID- 17175040
TI  - Statins in heart failure. Beyond the lipid lowering effect.
AB  - Statins, the most widely prescribed medications in patients with hyperlipidemia
      and coronary heart disease, have a number of pleiotropic actions beyond
      cholesterol lowering. They improve endothelial function, they have antioxidant
      and anti-inflammatory effects, they regulate neovascularization and have
      immunomodulatory activities. Experimental evidence suggests that statins may be
      beneficial in heart failure as they can inhibit myocardial hypertrophy, reduce
      cardiomyocyte loss by apoptosis, reduce oxidative stress and restore
      neurohormonal imbalance. Furthermore small randomised clinical trials showed that
      short term statin administration may improve key pathophysiological aspects of
      this syndrome. Finally retrospective analyses of large statin trials imply a long
      term profit on clinical outcome in this group of patients. These results however
      need to be reviewed with caution as certain studies have demonstrated that low
      serum cholesterol is associated with worse prognosis in HF and that ubiquinone
      levels, a micronutrient with antioxidant actions, reduces significantly following
      statin administration. Large prospective randomised controlled trials are needed
      to confirm the beneficial effect of statins on cardiovascular outcome in HF
      patients and further elucidate the contributing mechanisms. Finally the statin
      dose and the interaction with co-administered drugs need to be studied.

PMID- 17175042
TI  - Aortic dissection complicating pregnancy following prophylactic aortic root
      replacement in a woman with Marfan syndrome.
AB  - Prophylactic aortic root replacement is the main factor explaining the increase
      in median probability of survival in Marfan syndrome (MFS) patients. In women
      with MFS, earlier root replacement has been suggested as a strategy to facilitate
      safe pregnancy. However, in this case report a pregnant patient with MFS who
      sustained a Type B aortic dissection in her second trimester, with fatal outcome,
      despite having had a prophylactic aortic root replacement five months prior to
      conception is described.

PMID- 17175041
TI  - Impaired vascular function in patients with Fontan circulation.
AB  - BACKGROUND: This study was performed to evaluate the endothelial function in
      Fontan patients, and to investigate the associated factors which influence the
      endothelial function in these patients. METHODS: Flow mediated dilatation (FMD)
      and nitroglycerin induced dilatation (NG) of the brachial artery, and intima
      media thickness (IMT) of common carotid artery (CCA) were measured in nonselected
      Fontan patients (n=44, age 5 to 29 years, median 14 years, 18 females) by means
      of high-resolution ultrasound according to the standard protocols. The results
      were compared to age and sex matched controls (n=25, age 5 to 27 years, median 13
      years, 10 females). RESULTS: Fontan patients presented significantly reduced FMD
      and NG compared with controls (FMD; 6.5+/-2.4 vs. 11.1+/-1.4%, p<0.001, NG;
      13.3+/-5.2 vs. 19.4+/-6.2%; p=0.035). Twenty two percent of Fontan patients
      presented pure endothelial dysfunction, and 34% of patients presented combined
      endothelial and smooth muscle dysfunction. Although there was no correlation
      between FMD and IMT, Fontan patients presented increased carotid IMT (0.44+/-0.07
      vs. 0.38+/-0.06 mm, p=0.008). In multivariate analysis, duration of exposure to
      chronic hypoxia was inversely correlated with FMD (p=0.117, hazards ratio=1.294,
      95% confidence interval=0.938-1.786). There was higher FMD in patients receiving
      angiotensin-converting enzyme inhibitors (ACEi) compared with those not receiving
      ACEi (7.0+/-2.5 vs. 5.5+/-2.2%, p=0.069). CONCLUSIONS: Endothelial dysfunction is
      more prevalent in Fontan patients compared with healthy controls, and the
      previous hypoxia is an independent factor. Although it is not statistically
      significant, those patients on treatment with ACEi seem to have better
      endothelial function.

PMID- 17175043
TI  - Hospitalization due to acute heart failure. Role of the precipitating factors.
AB  - BACKGROUND AND AIMS: Many precipitating factors for decompensation of a chronic,
      stable heart failure (HF) have been described. OBJECTIVES: To evaluate the
      precipitating factors associated with HF decompensation among 293 patients
      admitted to a teaching hospital because of acute HF. RESULTS: 173 women and 120
      men were included, and mean age was 76.7 years. In 221 patients (75%) there was
      some evidence of a factor that was potentially accountable for the decompensation
      of HF; a combination of two or more factors could be elicited in 100 patients.
      Except for a worse prior functional status, no differences were found between
      patients with and without identified precipitating factors. CONCLUSIONS:
      Precipitating factors may be identified in most patients suffering an acute
      episode of decompensation of HF. The majority of these factors appear to be
      preventable, and should thus be avoidable with a better, more comprehensive
      control of the HF patient.

PMID- 17175044
TI  - Effects of verapamil on superior vena cava electrical remodeling induced by short
      term pacing from right atrium and superior vena cava in human.
AB  - BACKGROUND: Although the superior vena cava (SVC) may be involved in the
      triggering or maintenance of atrial fibrillation (AF), the electrophysiological
      properties of SVC in human are ill-defined. METHODS: The baseline effective
      refractory periods (ERPs) of high right atrium (HRA), SVC and the conduction time
      (CT) between HRA and SVC were measured at pacing cycle lengths (PCL) of 600 and
      400 ms respectively in 20 patients (12 females, age 46+/-13 years) with
      paroxysmal supraventricular tachycardia. Immediately after acute electrical
      remodeling (ER) induced by constant HRA or SVC pacing at PCL of 400 ms for 5 min,
      ERPs of HRA, SVC and the CT between HRA and SVC were determined. After verapamil
      was administered, the same protocols for determining ERPs of HRA, SVC and the CT
      between HRA and SVC were repeated. RESULTS: The baseline ERP of SVC was
      significantly longer than that of HRA. The CT from SVC to HRA was significantly
      longer than that from HRA to SVC. After acute ER, both the ERPs of HRA and SVC
      were significantly shortened. However, no significant changes of the CT between
      HRA and SVC could be demonstrated. After verapamil infusion, significant
      shortening of the ERP of HRA and SVC still occurred following acute ER and the
      ERP of SVC was still longer than that of HRA. CONCLUSIONS: In human, ER can occur
      both in HRA and SVC after a short and moderately rapid heart rate pacing either
      from HRA or SVC. Verapamil cannot prevent such ER from occurring.

PMID- 17175045
TI  - Cardiovascular magnetic resonance findings in typical versus atypical forms of
      the acute apical ballooning syndrome (Takotsubo cardiomyopathy).
AB  - To assess cardiovascular magnetic resonance (CMR) findings in Takotsubo
      cardiomyopathy (TTC), 17 consecutive patients (15 women) with TTC who underwent
      left heart catheterization and gadolinium-enhanced CMR were evaluated. All
      patients had an abnormal electrocardiogram consisting of ST-segment elevation
      (n=8) and/or ST-segment depression (n=4) and/or T-wave inversion (n=14). One
      patient presented with left-bundle branch block. Left ventricular apical segments
      were involved in 10 patients (classical TTC), while they were not affected in 7
      (variant form). Mean time delay between presentation and CMR was 9+/-7 days
      (range 3-24 days). CMR demonstrated complete resolution (n=4) or significant
      improvement of initial WMA in all cases. WMA were confined to basal and mid
      ventricular segments (segments 1-12 in the 17-segment model) in the variant form,
      while they were virtually confined to the mid and apical left ventricle (segments
      7-17) in classical TTC. Upon presentation ejection fraction by ventriculography
      was lower in classical TTC (36+/-7% vs. 58 +/-8%, p=0.0001). However, upon follow
      up ejection fraction by CMR was not different between classical and variant TTC
      (49+/-9% vs. 56+/-11%, p=0.23). Delayed hyperenhancement was absent in all but
      one patient. This finding may help differentiate TTC from entities with similar
      clinical presentations such as myocarditis and myocardial infarction, as the
      latter typically exhibits a subendocardial pattern of delayed hyperenhancement
      while the former usually displays a patchy subepicardial pattern.

PMID- 17175047
TI  - Quality control using a multilevel logistic model for the Danish pig Salmonella
      surveillance antibody-ELISA programme.
AB  - In Denmark, the level of Salmonella infection in pig herds is monitored with a
      surveillance programme using an indirect antibody ELISA. Our purpose with the
      present study was to determine whether sample results from the programme were
      useful in the quality control of this ELISA. Test results from the year 2003, in
      which the laboratory experienced a technical problem with an automatic microtitre
      plate washing machine, were examined statistically. We chose 3 months for the
      analysis: January, where the problem was moderate, June with the problem more
      serious, and November, where the problem had been solved. A logistic analysis was
      carried out with outcome 0 for a negative test result and 1 for a positive test
      result. Row and column on the microtitre plates, multiprobe robot, and their
      interactions were included as fixed effects, and date, plate, and slaughterhouse
      were included as random effects. Backward elimination was carried out using
      alpha=0.05 to achieve a final model for each month. The row and the column were
      significant in January and June, and a robot effect was also included in the
      model for January. In June, an interaction between row and column was identified.
      In November, none of the fixed effects was significant. Breaking the months
      January and June into shorter time intervals showed that the row and column
      effects were significant also when data were from only 1 week, whereas the robot
      main effect was not significant in most periods and the interaction effects were
      not significant throughout. Analysis of the test results from the wells with test
      samples gave good information on systematic errors across the microtitre plates,
      and severe errors appeared significant even when data from short time periods
      were used.

PMID- 17175046
TI  - Acute and mid-term local vascular effects of compliant balloon inflation
      (GuardWire system) on saphenous vein bypass grafts: an angiographic analysis.
AB  - BACKGROUND: The GuardWire distal protection device reduces the incidence of
      periprocedural complications during percutaneous stenting of diseased saphenous
      vein grafts. Its mechanism of action is based on the occlusion of the vessel
      distal to the lesion with an inflated compliant balloon before the intervention,
      and the aspiration of embolized material after stent implantation. Although no
      safety issues related to the compliant balloon have been reported in vein graft
      treatment, concerns related to the potential injury of the balloon on the vessel
      wall have been raised. We thus evaluated the angiographic outcome of the vein
      graft segment where the compliant balloon of the GuardWire distal protection
      device was inflated during percutaneous interventions of diseased vein grafts.
      METHODS: Forty consecutive patients undergoing vein graft stenting, all with
      successful delivery of the GuardWire system, were enrolled. All patients
      underwent 6-months follow-up angiography. Quantitative coronary angiographic
      analysis of the vein graft segment where the balloon was inflated was performed
      before and after the procedure, as well as at 6-month follow-up. RESULTS: No
      differences in reference vessel diameter, minimal luminal diameter and diameter
      stenosis were evident between the three measurements. In particular, the
      difference between post-procedural and follow-up minimal luminal diameter (namely
      late loss) was 0.003+/-0.19 mm (95% confidence interval: -0.06-0.06).
      CONCLUSIONS: This prospective study supports for the first time the "angiographic
      safety" of low pressure inflations of a compliant balloon in saphenous vein
      grafts, suggesting the absence of acute and mid-term effects on the vein graft
      vessel wall.

PMID- 17175048
TI  - Remote sensing based identification of environmental risk factors associated with
      West Nile disease in horses in Camargue, France.
AB  - Geographic information system and remote sensing technologies were used to
      identify landscape features associated with risk of West Nile virus transmission
      as defined by the presence of confirmed horse cases. SPOT-4 images of Camargue
      area were used to generate a map of landscape categories of epidemic foci and the
      geographic information system was employed to determine the proportion of
      landscape components surrounding 10 horse case sites and 17 control sites. The
      spatio-temporal analysis of the cases outbreak gave the best results for a
      spatial window of 9 km and a temporal window of 18 days. Two clusters were
      identified (relative risk=3.35), both in the wet area of Camargue, near the town
      "Les Saintes Maries de la Mer". The first one was 4 km radius, the second 9 km.
      The relationships between the presence of cases and proportions of landscape
      categories were analyzed using generalized linear model. The best model indicated
      that rice fields and dry bushes, wet "sansouire" and open water were the major
      components of the landscape that were associated with the presence of West Nile
      virus cases.

PMID- 17175049
TI  - Space-time interaction as an indicator of local spread during the 2001 FMD
      outbreak in the UK.
AB  - During the 2001 FMD outbreak in the UK, decisions on the level of implementation
      of control measures were supported by predictive models. Models were mainly used
      as macro-level tools to predict the behaviour of the disease in the whole country
      rather than at the local level. Here we explore the use of the magnitude and
      characteristics of the space-time interaction as an indicator of local spread
      and, indirectly, of the effectiveness of control measures aimed at reducing short
      range transmission during the course of a major livestock disease epidemic. The
      spatiotemporal evolution patterns are described in the four main clusters that
      were observed during the outbreak by means of the hazard rate and space-time K
      function (K(s,t)). For each local outbreak, the relative measure D(0)(s,t),
      derived from K(s,t), which represents the excess risk attributable to the space
      time interaction was calculated for consecutive 20-day temporal windows to
      represent the dynamics of the space-time interaction. The dynamics of the
      spatiotemporal interaction were very different among the four local clusters,
      suggesting that the intensity of local spread, and therefore the effectiveness of
      control measures, markedly differed between local outbreaks. The large
      heterogeneity observed in the relative impact of being close in time and space to
      an infected premises suggests that the decision making in relation to control of
      the outbreak would have benefited from indicators of local spread which could be
      used to complement global predictive modelling results. Despite its limitations,
      our results suggest that the real-time analysis of the space-time interaction can
      be a valuable decision support tool during the course of a livestock disease
      epidemic.

PMID- 17175050
TI  - Salmonella Dublin infection in young dairy calves: transmission parameters
      estimated from field data and an SIR-model.
AB  - In this study we used field data collected from October 2001 to January 2002 to
      estimate number of days of faecal excretion of Salmonella Dublin bacteria and
      time to seroconversion in infected calves below the age of 180 days. Based on
      these estimates all calves in four endemically infected dairy herds were grouped
      into the following infection states: susceptible (S), infectious (I) and
      resistant/recovered (R). Resistant calves had either acquired maternal antibodies
      through colostrum or they have recovered from previous infection and had a high
      level of antibodies directed against Salmonella Dublin possibly protecting them
      from becoming infected again until the level of antibodies had decreased to
      sufficiently low levels. Using the antibody measurements and faecal excretion
      periods, it was possible to assign the most likely infection state to each calf
      per week of the study period. Estimates of transmission parameter, beta, were
      obtained from a generalised linear model relating the number of new infections to
      the proportion of susceptible and infectious calves per week. From beta, the
      reproduction ratio R at steady state and the basic reproduction ratio R(0) were
      estimated for each herd and across herds. The R(0) denotes the average number of
      new infections caused by one infectious individual that is introduced to a fully
      susceptible population. The point estimates for R(0) ranged from 1.1 to 2.7 in
      the study herds. However, the confidence intervals were wide. Data were too
      limited to show possible significant differences in the parameters between the
      study herds. However, the tendency in the data suggested that there may be
      important differences. Across herds the R(0) was close to two suggesting that on
      average one infectious calf will produce two new infectious calves when
      introduced into a fully susceptible population under typical Danish dairy
      production systems. Further, the analyses indicated that environmental
      contamination from infectious calves plays an important role in transmitting
      Salmonella Dublin between calves.

PMID- 17175051
TI  - A new antimicrobial susceptibility testing method of Escherichia coli against
      ampicillin by MSPQC.
AB  - A new antimicrobial susceptibility testing method by multi-channel series
      piezoelectric quartz crystal (MSPQC) was proposed. This method was used to test
      susceptibility of clinical Escherichia coli isolates against ampicillin. Both the
      minimum inhibitory concentrations (MICs) and interpretive categorization of
      clinical E. coli isolates were determined by proposed method. Comparing tests
      were run at the same time by the agar dilution method and the disk diffusion
      method. The experimental results showed that MSPQC method had a good agreement
      with the reference methods. Compared with those methods, the MSPQC method is
      simple, rapid, and convenient to perform. It can offer both a minimum inhibitory
      concentration (MIC) and an interpretive category result.

PMID- 17175052
TI  - Meta-analysis for microarray studies of the genetics of complex traits.
AB  - In comparison to other complex disease traits, alcoholism and alcohol abuse are
      influenced by the combined effects of many genes that alter susceptibility,
      phenotypic expression and associated morbidity, respectively. Many genetic
      studies, in both animal models and humans, have identified genetic intervals
      containing genes that influence alcoholism or behavioral responses to ethanol.
      Concurrently, a growing number of microarray studies have identified gene
      expression differences related to ethanol drinking or other ethanol behaviors.
      However, concerns about the statistical power of these experiments, combined with
      the complexity of the underlying phenotypes, have greatly hampered the
      identification of candidate genes underlying ethanol behaviors. Meta-analysis
      approaches using recent compilations of large datasets of microarray, behavioral
      and genetic data promise improved statistical power for detecting the genes or
      gene networks affecting ethanol behaviors and other complex traits.

PMID- 17175053
TI  - Study of a room temperature phosphorescence phenomenon to allow the detection of
      aflatoxigenic strains in culture media.
AB  - A novel screening method based on room temperature phosphorescence (RTP) for the
      visual detection of aflatoxigenic strains from Aspergillus genus is described.
      Strains were cultured on media widely used in food mycology to which methyl-beta
      cyclodextrin plus bile salts (0.6% sodium deoxycholate) were added. Aflatoxin
      production was readily detectable after 3 days of incubation at 28 degrees C by
      RTP emission from the mycelium of aflatoxigenic strains observed after exposure
      to UV light. The method was tested on thirty-two Aspergillus sp. strains. The
      phosphorescence phenomenon was reproduced in vitro by immobilizing aflatoxin B1
      on ion exchange resin beads.

PMID- 17175054
TI  - Predictive modelling of temperature and water activity (solutes) on the in vitro
      radial growth of Botrytis cinerea Pers.
AB  - The objective of this work was to develop validated models predicting the 'in
      vitro' effect of a(w) and temperature on the radial growth of Botrytis cinerea.
      The growth rate (g, mm d(-1)) of B. cinerea was calculated at three incubation
      temperatures (25 degrees C, 15 degrees C, 5 degrees C) and six water activities
      (ranging from 0.995 to 0.890). The water activity was adjusted with glucose,
      NaCl, glycerol, or sorbitol. Statistical analysis showed a significant effect of
      temperature, solute, a(w), and their two- and three-way interactions on the
      growth rate. No growth was observed at a(w)=0.93 in the presence of NaCl or at
      0.89 in the presence of a non-ionic solute. The maximum colony growth rate
      decreased when the incubation temperature and water activity was lowered.
      Secondary models, relating the colony growth rate with a(w) or a(w) and
      temperature were developed. Optimum a(w) values for growth ranged from 0.981 to
      0.987 in glycerol-, sorbitol-, or glucose-modified medium and were close to 1 in
      NaCl-modified medium. A quadratic polynomial equation was used to describe the
      combined effects of temperature and a(w) on g (mm d(-1)) in the presence of each
      solute. The highest and lowest radial growth rates were observed in models based
      on glucose and NaCl respectively, whatever the incubation temperature. All models
      prove to be good predictors of the growth rates of B. cinerea within the limits
      of experiments. The quadratic polynomial equation has bias factors of 0.957,
      1.036, 0.950, and 0.860 and accuracy factors of 1.089, 1.070, 1.120 and 1.260 in
      media supplemented with glucose, NaCl, glycerol and sorbitol respectively. The
      results from modelling confirm the general finding that a(w) has a greater
      influence on fungal growth than temperature.

PMID- 17175055
TI  - Presence of aflatoxin M1 in pasteurized milk from Morocco.
AB  - Fifty four samples of pasteurized milk produced by five different dairies from
      Morocco were surveyed for the presence of aflatoxin M1 (AFM1) using
      immunoaffinity columns and liquid chromatography coupled to fluorescence
      detection. Confirmation of AFM1 identity in positive samples was based on the
      formation of AFM1 hemi-acetal derivative (AFM2a) after derivatization with
      trifluoracetic acid. Analytical results showed that 88.8% of the samples were
      contaminated with AFM1; 7.4% being above the maximum level of 0.05 microg/L set
      by the Moroccan and European regulations for AFM1 in liquid milk. The incidence
      of AFM1 in milk from these dairies was 100, 92.3, 90, 83.3 and 77.7%
      respectively, with AFM1 levels ranging from 0.001 to 0.117 microg/L and a mean
      value of 0.0186 microg/L. Based on the results presented in this study, the
      estimated daily intake of AFM1 was 3.26 ng/person/day. In this work, data on the
      natural occurrence of AFM1 in pasteurized milk produced in Morocco is presented
      for the first time.

PMID- 17175056
TI  - Stabilization of alpha-chymotrypsin by covalent immobilization on amine
      functionalized superparamagnetic nanogel.
AB  - Stabilization of alpha-chymotrypsin (CT) by covalent immobilization on the amine
      functionalized magnetic nanogel was studied. The amino groups containing
      superparamagnetic nanogel was obtained by Hoffman degradation of the
      polyacrylamide (PAM)-coated Fe(3)O(4) nanoparticles prepared by facile
      photochemical in situ polymerization. CT was then covalently bound to the
      magnetic nanogel with reactive amino groups by using 1-ethyl-3-(3
      dimethylaminepropyl) carbodiimide as coupling reagent. The binding capacity was
      determined to be 61mg enzyme/g nanogel by BCA protein assay. Specific activity of
      the immobilized CT was measured to be 0.93U/(mgmin), 59.3% as that of free CT.
      The obtained immobilized enzyme had better resistance to temperature and pH
      inactivation in comparison to free enzyme and thus widened the ranges of reaction
      pH and temperature. The immobilized enzyme exhibited good thermostability,
      storage stability and reusability. Kinetic parameters were determined for both
      the immobilized and free enzyme. The value of K(m) of the immobilized enzyme was
      larger than did the free form, whereas the V(max) was smaller for the immobilized
      enzyme.

PMID- 17175057
TI  - Random strand transfer recombination (RSTR) for homology-independent nucleic acid
      recombination.
AB  - Random strand transfer recombination (RSTR) relies on the ability of viral
      reverse transcriptases to undergo homology-independent template switches during
      DNA synthesis. To facilitate strand transfer events single stranded template DNA
      was hybridized via noncoding complementary sequence stretches which flank the
      genes. The resulting bulb shaped heteroduplex was used as template for the
      reverse transcriptase driven DNA polymerization in which template switch events
      occur spontaneously. Switches were promoted by induced pausing of the viral
      polymerase at digoxygenin labeled nucleotides. RSTR of homologous genes was
      demonstrated by the recombination of two genes encoding (R)-hydroxynitrilase
      isoenzymes from Prunus amygdolus. For non-homologous RSTR we recombined the genes
      of the Havea brasiliensis (S)-hydroxynitrilase and the estC gene from
      Burkholderia gladioli. Base-pairing dependent recombination took place
      spontaneously and at high frequency between genes with low and high sequence
      homology.

PMID- 17175058
TI  - Polymorphisms of dopamine receptor/transporter genes and risk of non-small cell
      lung cancer.
AB  - BACKGROUND: The dopaminergic pathway may be of interest in assessing risk of non
      small cell lung cancer (NSCLC). Dopamine receptors are expressed in alveolar
      epithelial cells and human lung tumours, and dopamine inhibits both cell
      proliferation in vitro and growth of lung tumour xenografts in nude mice.
      Moreover, dopamine selectively inhibits the vascular permeability and angiogenic
      activity of vascular endothelial growth factor (VPF/VEGF). The bioavailability of
      dopamine is regulated by dopamine receptors D2 (DRD2), D4 (DRD4) and dopamine
      transporter 1 (DAT1/SLC6A3) genes. METHODS: We have analysed 10 single nucleotide
      polymorphisms in DRD2, DRD4 and DAT1/SLC6A3 genes in relation to lung cancer risk
      in a case-control study of smoking subjects. The study subjects were 413 healthy
      individuals from general population and 335 NSCLC cases. Both cases and controls
      were Caucasians of Norwegian origin. RESULTS: We demonstrate that DRD2
      polymorphisms -141Cdel, 3208G>T, TaqIB; DRD4 -521C>T and DAT1/SLC6A3 -1476T>G are
      associated with a two- to five-fold increased NSCLC risk. The variant alleles of
      DRD2 1412A>G and 960C>G had protective effects. CONCLUSION: The dopamine
      receptor/transport gene polymorphisms are associated with the risk of NSCLC among
      smokers. The data show that the polymorphisms resulting in lower dopamine
      bioavailability were associated with increased risk of NSCLC.

PMID- 17175059
TI  - Interleukin-8 stimulates cell proliferation in non-small cell lung cancer through
      epidermal growth factor receptor transactivation.
AB  - Interleukin-8 (IL-8; CXCL8) is a cytokine of the CXC chemokine family that is
      involved in neutrophil recruitment and activation. In addition, IL-8 has been
      implicated in a wide variety of other processes, including angiogenesis and
      metastasis in lung cancer. Lung adenocarcinoma and muco-epidermoid carcinoma
      cells produce substantial amounts of IL-8, and express both CXCR1 and CXCR2 IL-8
      receptors. We hypothesized that IL-8 stimulates proliferation of non-small cell
      lung cancer cells, involving transactivation of the epidermal growth factor
      receptor (EGFR). The EGFR plays a central role in regulating cell proliferation
      and it has been therefore implicated in lung cancer. Both EGFR ligands and
      transactivation of the receptor may lead to downstream signalling events,
      including mitogen-activated protein kinase (MAPK) activation. Transactivation of
      the EGFR has been shown to occur in response to ligands of various G-protein
      coupled receptors (GPCRs) and involves metalloproteinase-mediated release of
      membrane bound EGFR ligands. The aim of the present study was to investigate the
      effect of IL-8 on proliferation of lung adenocarcinoma and muco-epidermoid
      carcinoma cells, and to explore the mechanisms leading to this proliferation in
      two different non-small cell lung cancer cell lines (A549 and NCI-H292). In both
      NSCLC cell lines, we observed that IL-8 stimulates epithelial cell proliferation
      in a dose-dependent manner. The ability of IL-8 to increase cell proliferation
      was blocked both by an inhibitor of EGFR tyrosine kinase, by a specific anti-EGFR
      blocking antibody and by a panmetalloproteinase inhibitor. Similar results were
      obtained using the GPCR inhibitor pertussis toxin. Inhibition of the MAPK p42/44
      (ERK1/2) also blocked the mitogenic effect of IL-8, while a p38 MAPK inhibitor
      did not affect IL-8-induced cell proliferation. These results suggest that IL-8
      increases cell proliferation in NSCLC cell lines via transactivation of the EGFR
      and that this mechanism involves metalloproteinase activity.

PMID- 17175060
TI  - Multiple Allee effects and population management.
AB  - Allee effects, strongly related to the extinction vulnerability of populations
      and gradually becoming acknowledged by both theoretically oriented and applied
      ecologists, have already been shown to have important roles in the dynamics of
      many populations. Although not yet widely recognized, two or more Allee effects
      can occur simultaneously in the same population. Here, we review the evidence for
      multiple Allee effects and show that their interactions can take several forms,
      many of which are far from inconsequential. We suggest that more research is
      needed to assess the prevalence and interactions of multiple Allee effects, as
      failing to take them into account could have adverse consequences for the
      management of threatened or exploited populations.

PMID- 17175061
TI  - Fractional calculus applied to the analysis of spectral electrical conductivity
      of clay-water system.
AB  - The analysis of the low-frequency conductivity spectra of the clay-water mixtures
      is presented. The frequency dependence of the conductivity is shown to follow the
      power-law with the exponent n=0.67 before reaching the frequency-independent
      part. When scaled with the value of the frequency-independent part of the
      spectrum the conductivity spectra for samples at different water content values
      are shown to fit to a single master curve. It is argued that the observed
      conductivity dispersion is a consequence of the anomalously diffusing ions in the
      clay-water system. The fractional Langevin equation is then used to describe the
      stochastic dynamics of the single ion. The results indicate that the
      experimentally observed dielectric properties originate in anomalous ion
      transport in clay-water system characterized with time-dependent diffusion
      coefficient.

PMID- 17175062
TI  - Changes in the antioxidant status in leaves of Solanum species in response to
      elicitor from Phytophthora infestans.
AB  - Three Solanum genotypes with various polygenic resistance levels to the oomycete
      pathogen Phytophthora infestans (Mont.) De Bary were studied for their
      antioxidant response to the pathogen culture filtrate (CF). Detached plant leaves
      were treated with CF for 6, 18 and 30 h, and assayed for changes in hydrogen
      peroxide content, total ascorbate and glutathione pools and redox ratios (reduced
      form to total pool), as well as for changes in activities of ascorbate
      peroxidase, glutathione reductase and glutathione-S-transferase. In CF treated
      leaves of non-host resistant S. nigrum var. gigantea and field resistant S.
      tuberosum cv Bzura, the H(2)O(2) content did not change in comparison to water
      treated control leaves, whereas in the susceptible S. tuberosum clone H-8105 it
      decreased below the control level. In CF treated leaves of all genotypes, the
      total ascorbate pools were relatively unaltered and their redox ratio changed
      only transiently. In Bzura leaves the total glutathione content increased earlier
      than in the two other genotypes. The glutathione redox ratio remained rather
      stable, except for the susceptible clone H-8105, where it decreased transiently
      by about 42%. The relative increases in activity of all the studied enzymes were
      the highest in the susceptible clone H-8105. The results are discussed in the
      light of oxidative processes occurring in CF treated leaves. We conclude that
      stringent control of pro- and anti-oxidant reactions bringing the H(2)O(2) and/or
      cellular redox state to the threshold level is decisive for deployment of an
      effective defense strategy.

PMID- 17175063
TI  - Response of sugarcane to increasing concentrations of copper and cadmium and
      expression of metallothionein genes.
AB  - Sugarcane (Saccharum spp.) offers the potential to be a phytoremediator species
      due to its outstanding biomass production, but its prospective metal accumulation
      and tolerance have not been fully characterized. Sugarcane plantlets were able to
      tolerate up to 100microM of copper in nutrient solution for 33 days, with no
      significant reduction in fresh weight, while accumulating 45mgCukg(-1) shoot dry
      weight. Higher levels of copper in solution (250 and 500microM) were lethal.
      Sugarcane displayed tolerance to 500microM Cd without symptoms of toxicity,
      accumulating 451mgCdkg(-1) shoot dry weight after 33 days, indicating its
      potential as Cd phytoremediator. DNA gel blot analyses detected 8 fragments using
      a metallothionein (MT) Type I probe, while 10 were revealed for the MT Type II
      and 8 for MT Type III. The number of genes for each type of MT in sugarcane might
      be similar to the ones identified in rice considering the interspecific origin of
      sugarcane cultivars. MT Type I gene appeared to present the highest level of
      constitutive expression, mainly in roots, followed by MT Type II, corroborating
      the expression pattern described based on large-scale expressed sequence tags
      sequencing. MT Type II and III genes were more expressed in shoots, where MT I
      was also importantly expressed. Increasing Cu concentration had little or no
      effect in modulating MT genes expression, while an apparent minor modulation of
      some of the MT genes could be detected in Cd treatments. However, the level of
      response was too small to explain the tolerance and/or accumulation of Cd in
      sugarcane tissues. Thus, cadmium tolerance and accumulation in sugarcane might
      derive from other mechanisms, although MT may be involved in oxidative responses
      to high levels of Cd. Sugarcane can be considered a potential candidate to be
      tested in Cd phytoremediation.

PMID- 17175064
TI  - Expression of three expansin genes during development and maturation of Kyoho
      grape berries.
AB  - Expansins are cell-wall-localized proteins that induce loosening of isolated
      plant cell walls in vitro in a pH-dependent manner, but exhibit no detectable
      hydrolase or transglycosylase activity. Three putative expansin cDNAs, Vlexp1,
      Vlexp2, and Vlexp3 were isolated from a cDNA library made from mature berries of
      the Kyoho grape. Expression profiles of the 3 genes were analyzed throughout
      berry development. Accumulation of the Vlexp3 transcript was closely correlated
      with berry softening, and expression of this gene was detected before veraison
      and markedly increased at veraison (onset of berry softening). Expression of
      Vlexp3 was berry-specific. Vlexp1 and Vlexp2 mRNA accumulation began during the
      expansion stage of berry development and expression increased for both genes
      during ripening. Vlexp1 and Vlexp2 mRNA was detected in leaf, tendril and flower
      tissues and Vlexp2 mRNA was additionally detected in root and seed tissues. These
      findings suggest that the three expansin genes are associated with cell division
      or expansion and berry ripening. Vlexp3, in particular, is most likely to play a
      role in grape berry softening at veraison.

PMID- 17175065
TI  - New techniques for the evaluation and therapeutic planning of patients with
      Klippel-Trenaunay syndrome.
AB  - BACKGROUND: Klippel-Trenaunay syndrome (KTS) is a well-known eponym for a
      capillary-lymphatic-venous malformation which is associated with soft tissue and
      skeletal hypertrophy, usually of one or more limbs. Plain films, sonograms,
      conventional venograms, and arteriograms have been employed for the evaluation of
      the disease. OBJECTIVE: To demonstrate the usefulness of multidetector computed
      tomography (MDCT) and fast 3-dimensional magnetic resonance imaging (3D-MR)
      venography for the assessment and therapeutic planning of patients with KTS.
      METHODS: A prospective study in 16 consecutive patients with KTS using MDCT and
      3D-MR venography, performed between January 2004 and January 2006 in a university
      hospital in Pamplona, Spain. RESULTS: In nearly all patients, persistent
      embryologic veins were observed, and in one subject aplasia/atresia of the whole
      deep venous system of the affected extremity was seen. In four individuals
      hypoplasia of the femoral vein was observed; one subject had duplication of the
      femoral vein, and in three patients aplasia/atresia of this vein was found. Only
      half of the patients had normal popliteal veins. In one patient, aneurysmal
      dilatation of the popliteal vein was detected, and in six subjects, aplasia of
      this vein was observed. The presence of geographic stains was suggestive of
      hypoplasia and/or aplasia of femoral and popliteal veins. LIMITATIONS: The small
      size of the group of patients with KTS, which is related to low incidence of the
      disease. CONCLUSIONS: MDCT and 3D-MR venography are extremely helpful for the
      global evaluation of patients with KTS. Information regarding soft tissue and
      bony anatomy as well as information about superficial and deep venous systems may
      be obtained with a single exam.

PMID- 17175067
TI  - Outbreak of burn wound infections by Salmonella enterica serovar Menston and the
      role of disinfectant testing in finding the cause of spread.

PMID- 17175066
TI  - A case of Churg-Strauss syndrome associated with antiphospholipid antibodies.
AB  - Churg-Strauss syndrome (CSS) is a systemic vasculitis affecting both small- and
      medium-sized blood vessels, almost invariably affecting the lung, and frequently
      associated with cutaneous involvement. Microvascular vaso-occlusion leading to
      digital gangrene is not a feature of CSS. We report an unusual case of a patient
      with CSS with antiphospholipid antibodies who developed severe digital gangrene
      in addition to cutaneous vasculitis. The presence of antiphospholipid antibodies
      is not a feature usually seen in association with CSS. While the full clinical
      spectrum of CSS is still being defined, the identification of additional features
      associated with this syndrome might help to better understand the pathogenesis of
      the disease and to have an impact on both management and prognosis.

PMID- 17175069
TI  - Comparative genomic analysis of allatostatin-encoding (Ast) genes in Drosophila
      species and prediction of regulatory elements by phylogenetic footprinting.
AB  - The role of the YXFGLa family of allatostatin (AST) peptides in dipterans is not
      well-established. The recent completion of sequencing of genomes for multiple
      Drosophila species provides an opportunity to study the evolutionary variation of
      the allatostatins and to examine regulatory elements that control gene
      expression. We performed comparative analyses of Ast genes from seven Drosophila
      species (Drosophila melanogaster, Drosophila simulans, Drosophila ananassae,
      Drosophila yakuba, Drosophila pseudoobscura, Drosophila mojavensis, and
      Drosophila grimshawi) and used phylogenetic footprinting methods to identify
      conserved noncoding motifs, which are candidates for regulatory regions. The
      peptides encoded by the Ast precursor are nearly identical across species with
      the exception of AST-1, in which the leading residue may be either methionine or
      valine. Phylogenetic footprinting predicts as few as 3, to as many as 17
      potential regulatory sites depending on the parameters used during analysis.
      These include a Hunchback motif approximately 1.2 kb upstream of the open reading
      frame (ORF), overlapping motifs for two Broad-complex isoforms in the first
      intron, and a CF2-II motif located in the 3'-UTR. Understanding the regulatory
      elements involved in Ast expression may provide insight into the function of this
      neuropeptide family.

PMID- 17175068
TI  - Enterostatin (APGPR) enhances memory consolidation in mice.
AB  - Enterostatin (APGPR) is a pentapeptide released from its precursor protein,
      procolipase. We found for the first time that enterostatin has memory-enhancing
      activity. Enterostatin enhanced memory consolidation after central or oral
      administration at a dose of 10 nmol/mouse or 300 mg/kg, respectively, in a step
      through type passive avoidance test in mice. The memory-enhancing activity of
      enterostatin was inhibited by pretreatment with lorglumide, an antagonist for
      cholecystokinin 1 (CCK1) receptor. However, enterostatin had no affinity for CCK
      receptors. These results suggest that enterostatin improves memory retention
      through CCK release.

PMID- 17175070
TI  - Lack of association of hepatic lipase polymorphisms with late-onset Alzheimer's
      disease.
AB  - Several polymorphisms in hepatic lipase (LIPC) are similar to apoE4 because they
      associate with cholesterol concentrations and, for rs6084, coronary artery
      disease (CAD). Since apoE4 is also a primary genetic risk factor for late-onset
      Alzheimer's disease (LOAD), LIPC single nucleotide polymorphisms (SNP)s represent
      excellent candidates for LOAD association studies. Because this issue has not
      been addressed previously, we evaluated LIPC SNP association with LOAD. In a
      population from the Religious Orders Study (ROS), rs6084 was nominally associated
      with LOAD odds (p=0.015 by chi(2) test). However, this association was not
      confirmed in two subsequent series based at the University of Kentucky (UKY,
      p=0.15) or the Mayo Clinic in Jacksonville (MCJ, p=0.97). Hence, rs6084 is not
      consistently associated with LOAD.

PMID- 17175071
TI  - Synthesis and antitumour evaluation of peptidyl-like derivatives containing the
      1,3-benzodioxole system.
AB  - In the scope of a research program aiming at the synthesis and pharmacological
      evaluation of novel possible antitumour prototype compounds, we described in this
      paper the synthesis of peptidyl-like derivatives containing the 1,3-benzodioxole
      system. The proliferation inhibitors tested against tumour cell lines identified
      the derivatives tyrosine (4f) and lysine (4 g) as the most active among them,
      presenting IC(50) values in micromolar range and are more active than Safrole.
      For the study on the embryonic development, Safrole did not show any selectivity
      in this latter assay, which indicates that Safrole acts as a 'cell cycle
      nonspecific' inhibitory agent. However, compound 4f presented a fair antimitotic
      effect, mainly on third cleavage and blastulae stages (38% and 1.7% of normal
      development, at 10 microg/mL), suggesting a time-dependent activity and a 'cell
      cycle-specific' agent action. Neither derivatives revealed hemolytic action in
      assay with mouse erythrocytes.

PMID- 17175072
TI  - [Endovascular repair of a tuberculous aortic false aneurysm].
AB  - INTRODUCTION: Aortic aneurysms are a well known but rare complication of
      tuberculosis. Their major complication is aneurysmal rupture, unforeseeable and
      lethal. EXEGESIS: Chest pain and hemoptoic expectoration revealed a false
      aneurysm of the aortic isthmus in a 48-year-old man. Endovascular repair with a
      stent graft was urgently undertaken. Tuberculosis was diagnosed 6 weeks
      thereafter by the growth of gastric juice cultures and medically treated. Most
      tuberculous aortic aneurysms are false aneurysms, caused by an adjacent
      tuberculous focus eroding the aortic wall. They present with pain, bleeding or as
      para-aortic masses. CONCLUSION: Tuberculous false aneurysms of the aorta
      necessitate an early intervention before they rupture. Surgical treatment remains
      the preferred option but endovascular repair with a stent graft is a therapeutic
      alternative, to be considered in high-risk surgical patients.

PMID- 17175073
TI  - [Pseudoachalasia due to amyloidosis treated by botulinum toxin].
AB  - INTRODUCTION: Pseudoachalasia mimics primary achalasia and can provoke serious
      complications in the elderly. CASE RECORD: A 84 years-old woman had dysphagia
      with recurrent pneumonia. Pseudoachalasia related to a multifocal primitive
      amyloidosis was diagnosed. Treatment with botulinum toxin injection during a
      gastric fibroscopy resulted in clinical improvement, still notable 15 months
      later. DISCUSSION: Botulinum toxin injection may be a useful tool in treatment of
      pseudoachalasia due to amyloidosis.

PMID- 17175074
TI  - A feasibility study on the adoption of e-learning for public health nurse
      continuing education in Taiwan.
AB  - The purpose of this study is to investigate the feasibility of developing e
      learning and to examine reasons for adopting or rejecting e-learning as an
      alternative way to conduct continuing education (CE) for public health nurses
      (PHNs). A nationwide-based cross-sectional study was conducted with a randomly
      selected sample of 233 PHNs in Taiwan. A structured questionnaire was used to
      collect data by mailing methods. The majority of PHNs (88.84%, n=207) showed an
      affirmative intention towards adopting e-learning as their one way of CE. Reasons
      for adopting e-learning included achieving life learning, fulfilling personal
      interests, time-saving, based on job needs, information diversity, flexible in
      time and space, self-regulatory learning, cost-effectiveness, less impact on
      family duties and life. Twenty-six PHNs (11.16%) who rejected e-learning as their
      way of CE indicated main reasons including poor computer competence, lack of
      personal computer and without internet access, heavy work load, heavy family
      duties, conflict with personal preference, heavy economic burden, lack of
      motivation, and low self-control. This study reveals a high feasibility of
      developing e-learning that coexists with other CE models (e.g. traditional
      instruction). Reasons analyses provide directions for decreasing barriers for
      developing a learning model of this new medium for nurses' CE.

PMID- 17175075
TI  - Effect of occlusion status on the time required for initiation of recovery in
      response to external disturbances in the standing position.
AB  - BACKGROUND: To examine whether occlusion status contributes to improvement of
      postural balance. METHODS: Thirty healthy adolescents (15 males and 15 females;
      mean age, 20.3; standard deviation (SD) 1.6 years) with no equilibrium or
      stomatognathic function abnormalities were examined. Occlusion is a term meaning
      "jaw clenching." Occlusion status was evaluated by measuring masseter activity
      using the EMG system. Balancing ability was evaluated using the EquiTest system,
      which measures sway of the center of gravity produced by rapid movement of force
      plates as an external disturbance (three intensity levels). The time required for
      initiation of recovery after application of the disturbance was calculated by
      measuring displacement of the center of foot pressure. Data were compared
      according to occlusion status. FINDINGS: Little difference in latency was
      observed following a small disturbances; however, the greater the disturbance the
      shorter the latency with occlusion, while without occlusion, latency increased
      with increasing disturbance. A statistically significant interaction (P<0.001)
      between occlusion and external disturbance was also found. INTERPRETATION: This
      study suggested that occlusion contributes to maintenance of postural balance and
      improvement of stability when unexpected sway occurs in the standing position.

PMID- 17175076
TI  - DNA damage and repair process in earthworm after in-vivo and in vitro exposure to
      soils irrigated by wastewaters.
AB  - In this study, DNA damage to earthworms (Eisenia fetida) after in vivo exposure
      to contaminated soils was measured by detecting DNA strand breakages (DSBs) and
      causality was analyzed through fractionation based bioassays. A non-linear dose
      response relationship existed between DNA damage and total soil PAHs levels. DNA
      damage, measured with the comet assay, and its repair process, were observed. To
      identify the chemical causality, an in vitro comet assay using coelomocytes was
      subsequently performed on the fractionated organic extracts from soils. The
      results showed that the PAHs in the soils were responsible for the exerting
      genotoxic effects on earthworms. When normalized to benzo(a)pyrene toxic
      equivalent (TEQ(BaP)), the saturation dose in the dose-response curve was about
      10ng TEQ(BaP) g(-1) soil (dw).

PMID- 17175077
TI  - Physiological responses of Alternanthera philoxeroides (Mart.) Griseb leaves to
      cadmium stress.
AB  - Aquatic macrophytes were found to be the potential scavengers of heavy metals
      from aquatic environment. In this study, several physiological responses of
      Alternanthera philoxeroides (Mart.) Griseb leaves to elevated concentrations of
      cadmium (up to 10mM) were investigated. It was found that A. philoxeroides was
      able to accumulate cadmium in its leaves. The pigment contents decreased with the
      increase of the Cd concentrations. The Cd could induce rise of the activity of
      peroxidase (POD) at lower concentration (<5mM), however, when the concentration
      of Cd rose up to 10mM, the POD activity declined. The changes of superoxide
      dismutase (SOD) and Catalase (CAT) activities were exactly opposite to that of
      POD. In the leaves of Cd-treated fronds, the amounts of three polypeptides with
      apparent molecular weights 80, 39 and 28kDa, respectively, were became visible in
      SDS-PAGE. The nature of these polypeptides remains to be determined.

PMID- 17175078
TI  - Is the effect of silicon on rice uptake of arsenate (AsV) related to internal
      silicon concentrations, iron plaque and phosphate nutrition?
AB  - Solution culture experiments were conducted to investigate the effects of silicon
      (Si) on arsenate (As(V)) uptake by rice. The addition of Si to the pretreatment
      or uptake solution significantly decreased shoot and root As concentrations
      (P<0.001 and P<0.05). The presence of Si in the pretreatment or uptake solution
      also significantly decreased shoot P concentrations (P<0.001). The data
      demonstrated that both internal and external Si inhibited the uptake of As and P.
      Results of As uptake kinetics showed that the mechanism of the effect of Si on
      arsenate uptake is not caused by direct competition for active sites of
      transporters with As. The effect of Si on As uptake was not entirely mediated
      through the effect of Si on P uptake. Although the addition of Si to pretreatment
      solutions still significantly decreased shoot and root As concentrations, the
      extent of reduction became smaller when rice roots were coated with iron plaque.

PMID- 17175079
TI  - Budburst phenology of white birch in industrially polluted areas.
AB  - Effects of environmental contamination on plant seasonal development have only
      rarely been properly documented. Monitoring of leaf growth in mountain birch,
      Betula pubescens subsp. czerepanovii, around a nickel-copper smelter at
      Monchegorsk hinted advanced budburst phenology in most polluted sites. However,
      under laboratory conditions budburst of birch twigs cut in late winter from trees
      naturally growing around three point polluters (nickel-copper smelter at
      Monchegorsk, aluminium factory at Kandalaksha, and iron pellet plant at
      Kostomuksha) showed no relationship with distance from the emission source. In a
      greenhouse experiment, budburst phenology of mountain birch seedlings grown in
      unpolluted soil did not depend on seedling origin (from heavily polluted vs.
      clean sites), whereas seedlings in metal-contaminated soil demonstrated delayed
      budburst. These results allow to attribute advanced budburst phenology of white
      birch in severely polluted sites to modified microclimate, rather than to
      pollution impact on plant physiology or genetics.

PMID- 17175080
TI  - Characterization of gas/particle concentrations and partitioning of
      polychlorinated biphenyls (PCBs) measured in an urban site of Turkey.
AB  - Air concentrations of polychlorinated biphenyls (PCBs) in both gas and particle
      phases were measured in an urban site (BUTAL-Merinos) of the city of Bursa,
      Turkey between August 2004 and May 2005. The mean of total (particle+gas) PCB
      concentrations was about 491.8+/-189.4pg/m(3). The main contributors for PCBs in
      the sampling site were the local sources and long-range atmospheric transport
      supported by back trajectory analysis. Lower molecular weight PCB congeners
      generally dominated in the samples. The particle phase of the measured PCBs
      accounted for 15% of the total PCB concentrations. Gas/particle distribution was
      investigated using different approaches such as log K(P)-log P(L)(o), log K(P)
      log K(OA) and the Junge-Pankow model. Regression analysis among log K(P), log
      P(L)(o) and log K(OA) exhibited significant correlation at p<0.05. Correlation
      between PCB homologs and meteorological parameters was formed to investigate the
      possible relationships.

PMID- 17175081
TI  - Where do Chinese scientists publish their research in environmental science and
      technology?

PMID- 17175082
TI  - A comprehensive model for reproductive and developmental toxicity hazard
      identification: II. Construction of QSAR models to predict activities of untested
      chemicals.
AB  - This report describes the construction, optimization and validation of a battery
      of quantitative structure-activity relationship (QSAR) models to predict
      reproductive and developmental (reprotox) hazards of untested chemicals. These
      models run with MC4PC software to predict seven general reprotox classes: male
      and female reproductive toxicity, fetal dysmorphogenesis, functional toxicity,
      mortality, growth, and newborn behavioral toxicity. The reprotox QSARs
      incorporate a weight of evidence paradigm using rats, mice, and rabbit reprotox
      study data and are designed to identify trans-species reprotoxicants. The
      majority of the reprotox QSARs exhibit good predictive performance properties:
      high specificity (>80%), low false positives (<20%), significant receiver
      operating characteristic (ROC) values (>2.00), and high coverage (>80%) in 10%
      leave-many-out validation experiments. The QSARs are based on 627-2023 chemicals
      and exhibited a wide applicability domain for FDA regulated organic chemicals for
      which they were designed. Experiments were also performed using the MC4PC
      multiple module prediction technology, and ROC statistics, and adjustments to the
      ratio of active to inactive (A/I ratio) chemicals in training data sets were made
      to optimize the predictive performance of QSAR models. Results revealed that an
      A/I ratio of approximately 40% was optimal for MC4PC. We discuss specific
      recommendations for the application of the reprotox QSAR battery.

PMID- 17175083
TI  - Neural mechanisms underlying trait impulsivity in non-clinical adults: stop
      signal performance and event-related potentials.
AB  - Impaired inhibitory processing has been implicated in clinical expressions of
      impulsivity, but it is unknown whether the same deficit underlies the personality
      trait in healthy, non-clinical populations. The present study examined
      performance and event-related potentials (ERPs) during a stop-signal task in non
      clinical adults who scored in the top ("Low" n=20) and bottom 15% ("High" n=20)
      on Eysenck's Impulsiveness Questionnaire from a sample of 200 subjects. The stop
      signal task consisted of a visual choice-RT task and auditory stop-signals
      presented on 30% of trials. While performance findings revealed no differences
      between groups, underlying ERPs revealed a number of quantitative differences.
      Lateralised readiness potential (LRP) amplitude on stop-signal trials was larger
      in the High than Low group, indicating greater response side-specific motor
      preparation in the primary motor cortex (PMC), while an N1/P3 complex was evoked
      on successful stop-signal trials and was also enhanced in the High than Low
      group. The centrally-maximal successful-stop P3 has previously been implicated as
      an index of inhibition in the PMC, suggesting enhanced inhibitory processing in
      the High group. Together these findings indicate that the High impulsivity group
      was able to counteract an impulsive response style on stop-signal trials with
      enhanced inhibitory activation, resulting in comparable overt performance to the
      Low group. These results provide a unique insight into the neural mechanisms
      underlying trait impulsivity in non-clinical adults.

PMID- 17175084
TI  - Evaluation of cardiovascular effects of caffeine using telemetric monitoring in
      the conscious rat.
AB  - Caffeine (1,3,7 trimethylxanthine) affects the cardiovascular system, with
      potential toxic effects ranging from a moderate increase in heart rate to more
      severe cardiac arrhythmias. Telemetry transmitters were implanted in Wistar rats
      in the peritoneal cavity with a pressure catheter in the aorta and electrodes for
      electrocardiogram (ECG) recording subcutaneously. After a single oral
      administration of saline, each rat was administered single oral doses of 5, 15
      and 45 mg/kg b.w. of caffeine. Caffeine was found to induce, to various degrees,
      a dose-dependent early increase in spontaneous physical activity, heart rate,
      dp/dt and systolic-diastolic blood pressure. No arrhythmias or visual changes
      were observed in the ECG complex. High doses induced more strong responses and of
      longer duration. The increase in systolic blood pressure at the median dose
      remained in the rats until 20 h after administration. However, the highest dose
      of caffeine (45 mg/kg b.w.) induced a biphasic response, with an early and
      pronounced increase in body temperature, spontaneous physical activity, systolic
      and diastolic blood pressure that later decreased, except for the systolic blood
      pressure. The results show that the dose level for long-lasting signs of
      intoxication to develop in the rat, in terms of effects on spontaneous physical
      activity, body temperature and cardiovascular function, was reached after a
      single oral dose of caffeine at 45 mg/kg b.w.

PMID- 17175085
TI  - Protein isolate from the herb, Phyllanthus niruri L. (Euphorbiaceae), plays
      hepatoprotective role against carbon tetrachloride induced liver damage via its
      antioxidant properties.
AB  - Phyllanthus niruri L. (Euphorbiaceae) (P. niruri) is a well-known
      hepatoprotective herbal plant. In the present study, hepatoprotective potential
      of the protein isolate of P. niruri was investigated against carbon tetrachloride
      (CCl(4)) induced liver damage in vivo. Protein isolate of P. niruri was
      intraperitoneally injected in mice either prior to (preventive) or after the
      induction of toxicity (curative). Levels of different liver marker enzymes in
      serum and different anti-oxidant enzymes, as well as lipid peroxidation products
      and glutathione (GSH) in liver homogenates were measured in normal, control
      (toxicity induced) and protein isolate treated mice. Administration of CCl(4)
      increased the serum glutamate pyruvate transaminase (GPT) and alkaline
      phosphatase (ALP) levels of mice sera along with increased lipid peroxidation and
      reduced levels of antioxidant enzymes superoxide dismutase (SOD) and catalase
      (CAT) in the liver. Treatment with the protein isolate of P. niruri significantly
      altered these changes to almost normal. The protein isolate also showed
      protective properties as was evidenced in histopathological studies. Results
      suggest that the protein isolate of P. niruri protects liver tissues against
      oxidative damage and somehow helps stimulating repair mechanism present in liver.
      It could be used as an effective hepatoprotector against CCl(4) induced liver
      damage.

PMID- 17175086
TI  - Cancer preventive properties of ginger: a brief review.
AB  - Ginger, the rhizome of Zingiber officinalis, one of the most widely used species
      of the ginger family, is a common condiment for various foods and beverages.
      Ginger has a long history of medicinal use dating back 2500 years. Ginger has
      been traditionally used from time immemorial for varied human ailments in
      different parts of the globe, to aid digestion and treat stomach upset,
      diarrhoea, and nausea. Some pungent constituents present in ginger and other
      zingiberaceous plants have potent antioxidant and anti-inflammatory activities,
      and some of them exhibit cancer preventive activity in experimental
      carcinogenesis. The anticancer properties of ginger are attributed to the
      presence of certain pungent vallinoids, viz. [6]-gingerol and [6]-paradol, as
      well as some other constituents like shogaols, zingerone etc. A number of
      mechanisms that may be involved in the chemopreventive effects of ginger and its
      components have been reported from the laboratory studies in a wide range of
      experimental models.

PMID- 17175087
TI  - ROS scavenging effects of organic extract of diesel exhaust particles on human
      neutrophil granulocytes and rat alveolar macrophages.
AB  - Diesel exhaust particles are major constituents of ambient air pollution, and are
      associated with respiratory and cardiovascular diseases and lung cancer. The
      organic part of the particles is heterogenic and complex, and seems to be
      responsible for many of the adverse effects. Increased formation of ROS is often
      connected to the adverse effects. We have therefore investigated the effect of an
      organic extract of diesel exhaust particles on the reactive oxygen species (ROS)
      status in human neutrophil granulocytes and rat alveolar macrophages in vitro.
      ROS formation were studied by three different assays namely the use of DCFH-DA,
      lucigenin and luminol. The organic extract increased ROS assayed with DCFH-DA,
      but it decreased the amount of ROS in cells stimulated by PMA in all three
      assays. The identities of the ROS affected were further studied in cell free
      systems. The cell free studies confirmed that the extract had scavenging effects
      against superoxide, hypochlorite and to a smaller extent against peroxynitrite,
      but not against the hydroxyl radical and nitric oxide. ROS take part in the
      intracellular signalling pathways as well as in the defence against invading
      microorganisms, and the possible effects of interference of the redox status in
      the cells are discussed.

PMID- 17175088
TI  - Inactivation and modification of superoxide dismutase by glyoxal: prevention by
      antibodies.
AB  - Glyoxal is an endogenous compound, the levels of which are increased in various
      pathologies associated with hyperglycaemia and other related disorders. It has
      been reported to inactivate critical cellular enzymes by promoting their cross
      linking and perpetuates advanced glycation end-product (AGE) formation. In this
      study, we used superoxide dismutase (SOD) as a model to investigate the ability
      of specific anti-enzyme antibodies and monomer Fab fragments to protect against
      glyoxal-induced deactivation and aggregate formation. We found that glyoxal
      deactivated SOD, in a concentration and time-dependent fashion. The enzymatic
      activity was monitored spectrophotometrically and it was found that enzyme lost
      approximately 95% of its original activity, when exposed to 10 mM glyoxal for 120
      h. SDS-polyacrylamide gel electrophoresis demonstrated the formation of high
      molecular weight aggregates in SOD samples exposed to glyoxal. Surface-enhanced
      laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS)
      showed increase in relative molecular mass (M(r)), upon exposure to glyoxal.
      Specific anti-enzyme antibodies and monomer Fab fragments markedly inhibited SOD
      deactivation caused by glyoxal and decreased the extent of cross-linking or
      formation of aggregates. This protection by the antibodies or Fab fragments was
      specific since, other non-specific antibodies were not able to protect SOD.
      Previously, antibodies have been used to prevent aggregation of beta-amyloid
      peptides in Alzheimer and prion-protein disease. Our findings provide a new
      perspective, for use of antibodies to prevent the biomolecules against glycation
      induced deactivation and alteration.

PMID- 17175090
TI  - Comparison of ventilation and chest compression performance by bystanders using
      the Impact Model 730 ventilator and a conventional bag valve with mask in a model
      of adult cardiopulmonary arrest.
AB  - "Bystanders" or lay persons are typically the first caregivers to attend to a
      victim of out-of-hospital cardiopulmonary arrest. Astronaut crew medical officers
      (CMO) play a similar role to bystanders aboard the International Space Station
      (ISS). Studies have demonstrated the importance of bystander cardiopulmonary
      resuscitation (BCPR) for patient survival before the arrival of emergency medical
      care. Recent apprehension from bystanders about the threat of contracting
      communicable diseases during BCPR, however, has led to the consideration of other
      ventilation systems such as the bag-valve mask (BVM) and automatic transport
      ventilators (ATV). BVM use is called for during CPR aboard the ISS. This study
      evaluated the ventilation and compression performance of 40 basic CPR-trained
      bystanders using either a BVM (adult-sized self-inflating bag with face mask) or
      an ATV (Model 730 ventilator (M730), Impact Instrumentation, Inc., West Caldwell,
      NJ). Each two-bystander team gave BCPR to a simulated cardiopulmonary arrest
      victim using the 2-breath/15-compression cycle for 4 min and then switched roles
      for another 4-min interval. Compared to BVM use, the M730 led to significantly
      (p<0.05) lower number of breaths, smaller tidal volumes, airway flows, airway
      pressures, volume of gas entering the stomach per breath and chest compressions
      for the 4-min period. The M730 also enabled a bystander to meet the
      recommendation of 4-breath and compression cycles per minute as per Guidelines
      2000. Lastly, ease-of-use scores were significantly higher for the M730 compared
      to the BVM. Overall, the data suggest that the M730 improves the quality of
      performance for a bystander performing BCPR.

PMID- 17175089
TI  - Identification of 3-deoxyglucosone dehydrogenase as aldehyde dehydrogenase 1A1
      (retinaldehyde dehydrogenase 1).
AB  - One of the metabolic fates of 3-deoxyglucosone, a product of protein deglycation
      and a potent glycating agent, is to be oxidized to 2-keto-3-deoxygluconate, but
      the enzyme that catalyzes this reaction is presently unknown. Starting from human
      erythrocytes, which are known to convert 3-deoxyglucosone to 2-keto-3
      deoxygluconate, we have purified to near homogeneity a NAD-dependent
      dehydrogenase that catalyzes this last reaction at neutral pH. Sequencing of a 55
      kDa band co-eluting with the enzymatic activity in the last step indicated that
      it corresponded to aldehyde dehydrogenase 1A1 (ALDH1A1), an enzyme known to
      catalyze the oxidation of retinaldehyde to retinoic acid. Overexpression of human
      ALDH1A1 in HEK cells led to a more than 20-fold increase in 3-deoxyglucosone
      dehydrogenase activity. In mouse tissues 3-deoxyglucosone dehydrogenase activity
      was highest in liver, intermediate in lung and testis, and negligible or
      undetectable in other tissues, in agreement with the tissue distribution of
      ALDH1A1 mRNA. 3-deoxyglucosone dehydrogenase activity was undetectable in tissues
      from ALDH1A1(-/-) mice. ALDH1A1 appears therefore to be the major if not the only
      enzyme responsible for the oxidation of 3-deoxyglucosone to 2-keto-3
      deoxygluconate. The urinary excretion of 2-keto-3-deoxygluconate amounted to 16.7
      micromol/g creatinine in humans, indicating that 3-deoxyglucosone may be
      quantitatively a more important substrate than retinaldehyde for ALDH1A1.

PMID- 17175091
TI  - Arsenite interactions with phospholipid bilayers as molecular models for the
      human erythrocyte membrane.
AB  - There are scanty reports concerning the effects of arsenic compounds on the
      structure and functions of cell membranes. With the aim to better understand the
      molecular mechanisms of the interaction of arsenite with cell membranes we have
      utilized bilayers of dimyristoylphosphatidylcholine (DMPC) and
      dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid
      classes located in the outer and inner monolayers of the human erythrocyte
      membrane, respectively. The capacity of arsenite to perturb the bilayer
      structures was determined by X-ray diffraction and fluorescence spectroscopy,
      whilst the modification of their thermotropic behaviour was followed by
      differential scanning calorimetry (DSC). The experiments carried out by X-ray
      diffraction and calorimetry clearly indicated that NaAsO(2) interacted with DMPE
      and modified its thermotropic behaviour. No such information has been so far
      reported in the literature.

PMID- 17175092
TI  - Investigation of C-H...O=C and N-H...OC hydrogen-bonding interactions in
      crystalline thymine by DFT calculations of O-17, N-14 and H-2 NQR parameters.
AB  - A computational study at the level of density functional theory (DFT) was carried
      out to investigate C-H...O=C and N-H...O=C hydrogen-bonding interactions (HBs) in
      the real crystalline cluster of thymine by O-17, N-14 and H-2 calculated nuclear
      quadrupole resonance (NQR) parameters. To perform the calculations, a hydrogen
      bonded pentameric cluster of thymine was created using X-ray coordinates where
      the hydrogen atoms positions are optimized and the electric field gradient (EFG)
      tensors were calculated for the target molecule. Additional EFG calculations were
      also performed for crystalline monomer and an optimized isolated gas-phase
      thymine. The calculated EFG tensors at the level of B3LYP and B3PW91 DFT methods
      and 6-311++G**and CC-pVTZ basis sets were converted to those experimentally
      measurable NQR parameters, quadrupole coupling constants and asymmetry
      parameters. The results reveal that because of strong contribution to N-H...O=C
      HBs, NQR parameters of O2, N1 and N3 undergo significant changes from monomer to
      the target molecule in cluster. Furthermore, the NQR parameters of O2 also
      undergo some changes because of non-classical C-H...O=C HBs.

PMID- 17175093
TI  - Indigenous community-based fisheries in Australia.
AB  - The commercial sea cucumber species known as Sandfish (Holothuria scabra) occurs
      intertidally and subtidally in the Northern Territory of Australia, on or
      adjacent to Aboriginal land. A 4-yr program of community-based fisheries research
      with Aboriginal Australians was implemented to assess the viability of indigenous
      Australians' involvement in the wild-stock fishery. The research involved
      extensive and intensive indigenous participation, unusual in Australian
      biophysical sciences research, during field survey and habitat mapping,
      complemented by commercial catch data modelling and discussion of its
      implications. Field surveys produced Sandfish distribution and site-specific
      density, and revealed some areas that were not commercially fished. Catch data
      modelling results suggested that no additional effort could be sustained, however
      commercial fishers increased their effort, expanding their operations into the
      newly mapped areas. These actions effectively precluded indigenous peoples'
      aspirations of entry into the commercial fishery. The efficacy and outcomes of
      participatory program design with indigenous Australians need critique in the
      absence of the political will and statutory backing to provide equitable access
      to resources.

PMID- 17175094
TI  - Scientific research, stakeholders, and policy: continuing dialogue during
      research on radionuclides on Amchitka Island, Alaska.
AB  - It is increasingly clear that a wide range of stakeholders should be included in
      the problem formulation phase of research aimed at solving environmental
      problems; indeed the inclusion of stakeholders at this stage has been formalized
      as an integral part of ecological risk assessment. In this paper, we advocate the
      additional inclusion of stakeholders in the refinement of research methods and
      protocols and in the execution of the research, rather than just at the final
      communication and reporting phase. We use a large study of potential radionuclide
      levels in marine biota around Amchitka Island as a case study. Amchitka Island,
      in the Aleutian Island Chain of Alaska, was the site of three underground nuclear
      tests (1965-1971). The overall objective of the biological component of the study
      was to collect a range of marine biota for radionuclide analysis that could
      provide data for assessing current food safety and provide a baseline for
      developing a plan to monitor human and ecosystem health in perpetuity.
      Stakeholders, including regulators (State of Alaska), resource trustees (US Fish
      and Wildlife Service, State of Alaska), representatives of the Aleut and Pribilof
      Island communities, the Department of Energy (DOE), and others, were essential
      for plan development. While these stakeholders were included in the initial
      problem formulation and approved science plan, we also included them in the
      refinement of protocols, selection of bioindicators, selection of a reference
      site, choice of methods of collection, and in the execution of the study itself.
      Meetings with stakeholders resulted in adding (or deleting) bioindicator species
      and tissues, prioritizing target species, refining sampling methods, and
      recruiting collection personnel. Some species were added because they were
      important subsistence foods for the Aleuts, and others were added because they
      were ecological equivalents to replace species deleted because of low population
      numbers. Two major refinements that changed the research thrust were (1) the
      inclusion of Aleut hunters and fishers on the biological expedition itself to
      ensure that subsistence foods and methods were represented, and (2) the addition
      of a fisheries biologist on a NOAA research trawler to allow sampling of
      commercial fishes. Although the original research design called for the
      collection of biota by Aleut subsistence fishermen, and by a commercial fishing
      boat, the research was modified with continued stakeholder input to actually
      include Aleuts and a fisheries biologist on the expeditions to ensure their
      representation. The inclusion of stakeholders during the development of protocols
      and the research itself improved the overall quality of the investigation, while
      making it more relevant to the interested and affected parties. Final
      responsibility for the design and execution of the research and radionuclide
      analysis rested with the researchers, but the process of stakeholder inclusion
      made the research more valuable as a source of credible information and for
      public policy decisions.

PMID- 17175095
TI  - Surgical management of renal cell carcinoma with tumor thrombus in the renal and
      inferior vena cava: the University of Miami experience in using liver
      transplantation techniques.
AB  - OBJECTIVES: Renal cell carcinoma (RCC) with tumor thrombus in the inferior vena
      cava (IVC) poses a challenge to the surgeon due to the potential for massive
      hemorrhage and tumor thromboemboli. We developed a technique for safe resection
      of these tumors through a transabdominal approach, without recourse to
      cardiopulmonary bypass (CPB). MATERIALS AND METHODS: From August 1997 to February
      2005, 66 patients underwent resection of a RCC with tumor thrombus in the IVC.
      The extent of the tumor thrombus was renal in 13, infrahepatic in 7; retrohepatic
      in 38; and intra-atrial in 8 patients. RESULTS: Mean operative time was 6.16+/
      0.32 hours. The estimated blood loss ranged from 200 cc to 16,000 cc, with a mean
      of transfusions being 3.56+/-0.94 U. CBP was required in only 3 patients. Three
      patients (4.5%) died in the immediate postoperative period. Median follow-up
      among the 56 survivors was 7.1 months. Six patients died due to metastasis and 1
      died of a cause unrelated to the cancer. The estimated actuarial survival at 36
      months was 66%. CONCLUSIONS: An aggressive surgical approach is the only hope for
      curing patients having RCC with a tumor thrombus in the IVC. The extent of
      dissection is predicated on the extent and level of tumor thrombus. Our surgical
      approach uses liver transplant techniques to mobilize the liver off the IVC and
      to separate the IVC from the posterior abdominal wall. This maneuver provides
      excellent exposure and enables safe vascular control of the IVC.

PMID- 17175096
TI  - Long-term results after primary microsurgical repair of ulnar and median nerve
      injuries. A comparison of common score systems.
AB  - OBJECTIVE: The aim of this retrospective study was to analyze the long-term
      results of primary repair of median and ulnar nerve lesions. Clinical influence
      factors for nerve reconstruction were investigated. Furthermore, current score
      systems were inquired and evaluated on their effectiveness to illustrate the
      success of repair. PATIENTS AND METHOD: Sixty-five patients with 71 lesions of
      the median and ulnar nerve were assessed on average 8.2 years after
      reconstruction. The results were classified according to the DASH (disability of
      arm, shoulder, and hand) Score, the Rosen's hand protocol and the Highet Scale.
      RESULTS: On average the patients regained 70% of their original hand function
      (evaluated by Rosen Score: median nerve 2.2/for ulnar nerve 1.92 out of 3.0).
      Although we noticed inferior motor recovery in ulnar nerve lesions, no
      significant differences between the overall results of both nerves were observed.
      Neither accompanying artery and flexor tendon injuries nor the suture technique
      influenced the recovery. The age of the patient was confirmed as an important
      influence factor. The results of the DASH Score, Rosen Score and Highet Score
      correlated significantly. CONCLUSION: For a sufficient outcome measurement we
      underline the importance of evaluation of patient's estimation of their impact on
      their activities of daily living. For this a combination of the functional Rosen
      Score and the DASH Score is suggested.

PMID- 17175097
TI  - Phosphorylation of ribosomal p70 S6 kinase and rapamycin sensitivity in human
      colorectal cancer.
AB  - We investigated the Akt-mTOR pathway and effects of rapamycin using human
      colorectal cancer cell lines. LoVo and CaRI reduced proliferative activity in
      response to rapamycin in a dose-dependent manner. The phosphorylation of Akt and
      p70 S6K was prominent in these cells. Rapamycin quickly downregulated phospho-S6K
      but not phospho-Akt. Therefore, phospho-S6K is considered a good indicator of the
      activated Akt-mTOR pathway as well as rapamycin sensitivity in colorectal cancer
      cells. By immunohistochemical study, nearly 40% of adenomas and carcinomas of the
      colorectum exhibited either partial or whole positive staining for phospho-S6K,
      suggestive of rapamycin-sensitive lesions.

PMID- 17175098
TI  - Adsorption of chromium(VI) on low cost adsorbents derived from agricultural waste
      material: a comparative study.
AB  - Two low cost adsorbents were prepared by using groundnut husk and were tested for
      the removal of chromium. All the experiments were carried out in batch process
      with chromium spiked samples of drinking water. Silver impregnated groundnut husk
      carbon and groundnut husk carbon were tested for the removal of chromium(VI).
      Effects of adsorbent quantity, pH, contact time and agitation rate were
      investigated on removal of chromium. The adsorption data were fitted well by
      Freundlich adsorption isotherm. Approximately, 97% of hexavalent chromium was
      removed at pH 3 within 5h. It was found that adsorbents chemically modified with
      an oxidizing agent demonstrated better chromium removal capabilities as compared
      to pure adsorbents in terms of their adsorption rate. On the basis of present
      studies, it can be concluded that groundnut husk carbon oxidized with silver
      treatment, has a higher chromium adsorption capacities.

PMID- 17175099
TI  - Quantitative estimation of uncertainty in human risk analysis.
AB  - This paper is aimed to candidate the use of an ISO standard procedure (Guide to
      the Expression of Uncertainty in Measurement, GUM) for quantitative evaluation of
      uncertainty in Human Risk estimation under chronic exposure to a hazardous
      chemical compound. Risk was evaluated by using the usual methodologies: the
      deterministic reasonable maximum exposure (RME) and the statistical Monte Carlo
      method; in both cases the procedures to evaluate the uncertainty on risk values
      are detailed. The paper put in evidence that the procedure is able to single out
      the variables that contribute mostly to the uncertainty. The obtained results
      show that the application of GUM procedure is easy and straightforward to
      estimate the uncertainty value on the results of risk estimation. The procedure
      is applied to a real case concerning the ingestion of milk contaminated by
      dioxins in a northern part of Italy; the risk value resulted to be over the
      minimal threshold of 10(-6) with 20-80% confidence.

PMID- 17175100
TI  - Preconcentration of Pb(II), Cr(III), Cu(II), Ni(II) and Cd(II) ions in
      environmental samples by membrane filtration prior to their flame atomic
      absorption spectrometric determinations.
AB  - A method for separation-preconcentration of Pb(II), Cr(III), Cu(II), Ni(II) and
      Cd(II) ions by membrane filtration has been described. The method based on the
      collection of analyte metal ions on a cellulose nitrate membrane filter and
      determination of analytes by flame atomic absorption spectrometry (FAAS). The
      method was optimized for several parameters including of pH, matrix effects and
      sample volume. The recoveries of analytes were generally in the range of 93-100%.
      The detection limits by 3 sigma for analyte ions were 0.02microgL(-1) for Pb(II),
      0.3microgL(-1) for Cr(III), 3.1microgL(-1) for Cu(II), 7.8microgL(-1) for Ni(II)
      and 0.9microgL(-1) for Cd(II). The proposed method was applied to the
      determination of lead, chromium, copper, nickel and cadmium in tap waters and RM
      8704 Buffalo River Sediment standard reference material with satisfactory
      results. The relative standard deviations of the determinations were below 10%.

PMID- 17175101
TI  - Acceleration after-effects on learning and memory in rats: +10 Gz or +6 Gz for 3
      min.
AB  - High sustained positive Gz (+Gz) exposures have been shown to have a
      pathophysiological impact on the brain in rats. However, the consequence for
      brain function such as learning and memory remains elusive. In the present study,
      we investigated locomotor activity, learning ability and memory in rats over 6
      days (d) following +6 Gz/3 min and +10 Gz/3 min exposures. In an open field test,
      rats treated with +10 Gz showed a significant increase in the time spent in the
      center square immediately and 2d after exposure compared with control rats. In
      contrast, the number of grid crosses and number of rears of rats decreased
      significantly immediately after +6 Gz and +10 Gz exposures. In addition, a Y-maze
      test revealed that +Gz exposures reduced the number of correct responses and
      increased total reaction time in rats, and the number of correct responses was
      negatively correlated with the total reaction time in all groups throughout the
      period of study. Moreover, the passive avoidance test exhibited that the latency
      increased significantly on 0 d and decreased significantly on 6 d after +Gz
      exposures compared with control. Thus, +6 Gz/3 min and +10 Gz/3 min exposures may
      transiently decrease locomotor activity, impair learning, and induce a deficit in
      memory retention in rats.

PMID- 17175104
TI  - Acetaminophen selectively suppresses peripheral prostaglandin E2 release and
      increases COX-2 gene expression in a clinical model of acute inflammation.
AB  - Acetaminophen is widely used for pain management as an alternative to NSAIDs and
      selective COX-2 inhibitors, but its action at a molecular level is still unclear.
      We evaluated acetaminophen's effect on PG release and the expression patterns of
      genes related to PG production in a clinical model of tissue injury and acute
      inflammation. Subjects (119 outpatients) received either 1000 mg acetaminophen,
      50 mg rofecoxib (a selective COX-2 inhibitor), 30 mg ketorolac (a dual COX-1/COX
      2 inhibitor), or placebo before the surgical removal of two impacted mandibular
      third molars. Microdialysis was used to collect inflammatory transudate from the
      surgical site for measurement of PGE2 and TXB2 levels at the site of injury.
      Biopsies were collected to investigate the expression patterns of genes related
      to PG production at baseline prior to surgery and at 3 or 24 h following surgery.
      PGE2 release was suppressed by ketorolac, rofecoxib and acetaminophen compared to
      placebo at 3 h coincident with increased COX-2 gene expression in biopsies
      collected from the surgical site. TXB2 release was suppressed only by ketorolac.
      COX-2 gene expression remained elevated at 24 h with continued ketorolac and
      acetaminophen treatment. COX-1 gene expression was significantly down-regulated
      at 24 h by ketorolac, rofecoxib and acetaminophen. Acetaminophen suppression of
      PGE2 without inhibiting TXB2 release, when COX-2 gene expression is up-regulated,
      suggests that acetaminophen is a selective COX-2 inhibitor in vivo. The up
      regulation of COX-2 gene and down-regulation of COX-1 gene expression suggests
      that acetaminophen may result in changes in COX-derived prostanoids with repeated
      doses.

PMID- 17175102
TI  - Autonomic and cardiovascular responses to scent stimulation are altered in cry KO
      mice.
AB  - Previously, we observed that in rats, olfactory stimulation with scent of
      grapefruit oil (SGFO) elevates the activities of sympathetic nerves. SGFO also
      suppresses gastric vagal (parasympathetic) nerve activity (GVNA), increases the
      plasma glycerol concentration, blood pressure (BP) and body temperature, and
      reduces appetite. In contrast, olfactory stimulation with scent of lavender oil
      (SLVO) has opposite effects in rats. Here, we show that in mice, olfactory
      stimulation with SGFO elevated activities of sympathetic nerves innervating the
      kidney, adrenal gland and brown adipose tissue as well as increasing BP and
      suppressing GVNA, whereas olfactory stimulation with SLVO decreased these
      sympathetic nerve activities and BP, and elevated GVNA. Electrolytic lesions of
      the mouse hypothalamic suprachiasmatic nucleus (SCN) eliminated changes in renal
      sympathetic nerve activity (RSNA), BP and GVNA induced by either SGFO or SLVO.
      Furthermore, SGFO-induced elevations in RSNA and BP and the SLVO-induced GVNA
      increase were not observed in Cryptochrome (Cry)-deficient mice, which harbor
      mutations in both cry1 and cry2 and lack normal circadian rhythms. These findings
      suggest that SGFO and SLVO affect autonomic neurotransmission and BP via the SCN
      in mice. Moreover, the molecular clock mechanism in the SCN, which involves the
      cry1 and cry2 genes, is partially involved in mediating these autonomic and
      cardiovascular actions of SGFO and SLVO.

PMID- 17175105
TI  - Diversity in the degree of sulfation and chain length of the glycosaminoglycan
      moiety of urinary trypsin inhibitor isomers.
AB  - Five isomers with different electric charge were fractionated from human urinary
      trypsin inhibitor (UTI) by anion exchange HPLC. Intact low-sulfated chondroitin 4
      sulfate chains from the isomers were analyzed by HPLC and mass spectrometry.
      Unsaturated disaccharide composition analysis of the chondroitin sulfate chain
      revealed that the five isomers differ in the numbers of 4-sulfated disaccharide
      units. Intriguingly, we detected the presence of multiple novel isomers with
      different numbers of non-sulfated disaccharide units even in the same charge
      isomer fraction. Our results demonstrate that UTI can vary in terms of both the
      degree of sulfation and the length of the low-sulfated chondroitin 4-sulfate
      chain.

PMID- 17175106
TI  - A randomized comparative trial between Acticoat and SD-Ag in the treatment of
      residual burn wounds, including safety analysis.
AB  - OBJECTIVE: To investigate and evaluate the clinical efficacy and safety of
      Acticoat with nanocrystalline silver for external use on the management of the
      residual wounds post-burn. METHODS: One hundred and sixty-six wounds of 98 burn
      patients were enrolled and divided into Acticoat group and silver sulfadiazine
      group in the multi-center randomized clinical trial. Acticoat was used as the
      treated group for those who have redness, swelling, and excessive secretion
      ("heavy" exudates) in the wound, Acticoat was changed once a day. When there is
      not much secretion in the wound, or redness and swelling were not obvious, the
      dressings were changed once every 3 days. Silver sulfadiazine (SD-Ag) was used as
      control group, which was treated under the usual clinical routine. Healing time
      was observed up to 20 days. Healing percentage on the 15th day after treatment
      was determined. RESULTS: Healing time was 12.42+/-5.40 days after the application
      of Acticoat. This was significantly shorter than that of control wounds. The
      wounds of the trial group healed nearly 3.35 days earlier than the control ones.
      Healing percentage at 15 days in the trial wounds was 97.37%, which was higher
      than the control, but there was no significant difference between them. The
      bacterial clearance rate of the Acticoat group on the 6th and 12th day post
      treatment was 16.67 and 26.67%, respectively, which was significantly higher than
      the control. CONCLUSIONS: Acticoat with nanocrystalline silver promotes the
      healing process of residual wounds post-burn effectively. No adverse reaction of
      Acticoat was found during the study.

PMID- 17175107
TI  - Chronic inhibition of cyclooxygenase-2 induces dendritic hypertrophy and limited
      functional improvement following motor cortex stroke.
AB  - The cyclooxygenase-2 (COX-2) enzyme is part of the inflammatory pathway and is
      induced within the brain by a variety of pathological events, including ischemia.
      Pharmacological agents that inhibit COX-2 have been found to be neuroprotective
      in a number of injury models, and long-term administration of these drugs has
      been shown to induce plastic changes in the brain. In the current experiment, we
      investigated the effectiveness of stimulating cortical plasticity following
      stroke injury through the administration of the COX-2 inhibitor drug NS398.
      Furthermore, we determined whether the induced plastic changes improved
      functional outcome following motor cortex stroke. Chronic drug administration was
      found to induce dendritic hypertrophy in cells in the parietal cortex, and this
      anatomical change was associated with the animals making significantly more reach
      attempts, as well as successful reaches during a skilled reaching task.
      Additional motor tests however revealed that the treatment did not affect the
      level of motor recovery, as the animals showed chronic impairments in the
      Schallert cylinder, and the forepaw inhibition tasks. Short-term administration
      of the drug, immediately following the stroke did not induce any dendritic
      changes, nor was it found to improve behavioral performance on any of the motor
      tasks. Based on these results we conclude that the plastic changes that are
      induced by long-term COX-2 inhibitor administration provide some benefit to
      functional outcome following ischemic cortical injury.

PMID- 17175108
TI  - Repair of methyl lesions in DNA and RNA by oxidative demethylation.
AB  - It was established several decades ago that it is crucial for all organisms to
      repair their DNA to maintain genome integrity and numerous proteins are dedicated
      to this purpose. However, it is becoming increasingly clear that it is also
      important to prevent and repair lesions in the macromolecules encoded by the DNA,
      i.e. RNA and protein. Many neurological disorders such as Alzheimer's disease and
      Parkinson's disease are associated with the aggregation of defective, misfolded
      proteins, and several mechanisms exist to prevent such aggregation, both through
      direct protein repair and through the elimination and repair of faulty or damaged
      RNAs. A few years ago, it was discovered that the E. coli AlkB protein
      represented an iron and 2-oxoglutarate dependent oxygenase capable of repairing
      methyl lesions in DNA by a novel mechanism, termed oxidative demethylation.
      Furthermore, it was found that both human and bacterial AlkB proteins were able
      to demethylate lesions also in RNA, thus representing the first example of RNA
      repair. In the present review, recent findings on the AlkB mechanism, as well as
      on RNA damage in general, will be discussed.

PMID- 17175109
TI  - Diabetic Goto-Kakizaki rats display pronounced hyperglycemia and longer-lasting
      cognitive impairments following ischemia induced by cortical compression.
AB  - Hyperglycemia has been shown to worsen the outcome of brain ischemia in several
      animal models but few experimental studies have investigated impairments in
      cognition induced by ischemic brain lesions in hyperglycemic animals. The Goto
      Kakizaki (GK) rat naturally develops type 2 diabetes characterized by mild
      hyperglycemia and insulin resistance. We hypothesized that GK rats would display
      more severe cerebral damage due to hyperglycemia-aggravated brain injury and,
      accordingly, more severe cognitive impairments. In this study, recovery of motor
      and cognitive functions of GK and healthy Wistar rats was examined following
      extradural compression (EC) of the sensorimotor cortex. For this purpose, tests
      of vestibulomotor function (beam-walking) and combined tests of motor function
      and learning (locomotor activity from day (D) 1 to D5, operant lever-pressing
      from D14 to D25) were used. EC consistently reduced cerebral blood flow in both
      strains. Anesthesia-challenge and EC resulted in pronounced hyperglycemia in GK
      but not in Wistar rats. Lower beam-walking scores, increased locomotor activity,
      impairments in long-term habituation and learning of operant lever-pressing were
      more pronounced and observed at later time-points in GK rats. Fluoro-Jade, a
      marker of irreversible neuronal degeneration, revealed consistent degeneration in
      the ipsilateral cortex, hippocampus and thalamus at 2, 7 and 14 days post
      compression. The amount of degeneration in these structures was considerably
      higher in GK rats. Thus, GK rats exhibited marked hyperglycemia during EC, as
      well as longer-lasting behavioral deficits and increased neurodegeneration during
      recovery. The GK rat is thus an attractive model for neuropathologic and
      cognitive studies after ischemic brain injury in hyperglycemic rats.

PMID- 17175110
TI  - beta(2)-Adrenoceptor-mediated facilitation of glutamatergic transmission in rat
      ventromedial hypothalamic neurons.
AB  - Adrenergic modulation of glutamatergic spontaneous miniature excitatory
      postsynaptic currents (mEPSCs) was investigated in mechanically dissociated rat
      ventromedial hypothalamic (VMH) neurons using a conventional whole-cell patch
      clamp technique. Noradrenaline (NA) reversibly increased mEPSC frequency without
      affecting the current amplitude in a concentration-dependent manner, indicating
      that NA acts presynaptically to facilitate the probability of spontaneous
      glutamate release. NA (10 microM) action on glutamatergic mEPSC frequency was
      completely blocked by 1 microM ICI-188551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H
      inden-4-yl)oxy]-3-[(1-methyl-ethyl)amino]-2-butanol], a selective beta(2)
      adrenoceptor antagonist, and mimicked by 1 microM formoterol, a selective beta(2)
      adrenoceptor agonist. Neither alpha-adrenoceptor nor beta(1)-adrenoceptor
      blockers affected the NA-induced increase in mEPSC frequency. NA action on
      glutamatergic mEPSC frequency was completely occluded in the presence of either
      10 microM forskolin, an adenylyl cyclase (AC) activator, or blocked by 1 microM
      SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine], a selective AC inhibitor.
      Furthermore, the NA-induced increase in mEPSC frequency was completely attenuated
      by either 1 muM KT5720 or 1 microM H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5
      isoquinolinesulfonamide), specific PKA inhibitors. However, NA still could
      increase mEPSC frequency either in the Ca(2+)-free external solution or in the
      presence of 1 microM thapsigargin. The results suggest that activation of
      presynaptic beta(2)-adrenoceptors facilitates spontaneous glutamate release to
      VMH neurons via cAMP/PKA signal transduction pathway. beta(2)-Adrenoceptor
      mediated presynaptic modulation of excitatory glutamatergic transmission would
      therefore be expected to play a pivotal role in the regulation of a variety of
      behavioral functions, which are mediated by the VMH.

PMID- 17175111
TI  - Glutamatergic innervation of the hypothalamic median eminence and posterior
      pituitary of the rat.
AB  - Recent studies have localized the glutamatergic cell marker type-2 vesicular
      glutamate transporter (VGLUT2) to distinct peptidergic neurosecretory systems
      that regulate hypophysial functions in rats. The present studies were aimed to
      map the neuronal sources of VGLUT2 in the median eminence and the posterior
      pituitary, the main terminal fields of hypothalamic neurosecretory neurons.
      Neurons innervating these regions were identified by the uptake of the retrograde
      tract-tracer Fluoro-Gold (FG) from the systemic circulation, whereas
      glutamatergic perikarya of the hypothalamus were visualized via the radioisotopic
      in situ hybridization detection of VGLUT2 mRNA. The results of dual-labeling
      studies established that the majority of neurons accumulating FG and also
      expressing VGLUT2 mRNA were located within the paraventricular, periventricular
      and supraoptic nuclei and around the organum vasculosum of the lamina terminalis
      and the preoptic area. In contrast, only few FG-accumulating cells exhibited
      VGLUT2 mRNA signal in the arcuate nucleus. Dual-label immunofluorescent studies
      of the median eminence and posterior pituitary to determine the subcellular
      location of VGLUT2, revealed the association of VGLUT2 immunoreactivity with SV2
      protein, a marker for small clear vesicles in neurosecretory endings. Electron
      microscopic studies using pre-embedding colloidal gold labeling confirmed the
      localization of VGLUT2 in small clear synaptic vesicles. These data suggest that
      neurosecretory neurons located mainly within the paraventricular, anterior
      periventricular and supraoptic nuclei and around the organum vasculosum of the
      lamina terminalis and the preoptic area secrete glutamate into the fenestrated
      vessels of the median eminence and posterior pituitary. The functional aspects of
      the putative neuropeptide/glutamate co-release from neuroendocrine terminals
      remain to be elucidated.

PMID- 17175112
TI  - Kir6.2-containing ATP-sensitive potassium channels protect cortical neurons from
      ischemic/anoxic injury in vitro and in vivo.
AB  - ATP-sensitive potassium (K(ATP)) channels are weak inward rectifiers that appear
      to play an important role in protecting neurons against ischemic damage. Cerebral
      stroke is a major health issue, and vulnerability to stroke damage is regional
      within the brain. Thus, we set out to determine whether K(ATP) channels protect
      cortical neurons against ischemic insults. Experiments were performed using
      Kir6.2(-/-) K(ATP) channel knockout and Kir6.2(+/+) wildtype mice. We compared
      results obtained in Kir6.2(-/-) and wildtype mice to evaluate the protective role
      of K(ATP) channels against focal ischemia in vivo, and, using cortical slices,
      against anoxic stress in vitro. Immunohistochemistry confirmed the presence of
      K(ATP) channels in the cortex of wildtype, but not Kir6.2(-/-), mice. Results
      from in vivo and in vitro experimental models indicate that Kir6.2-containing
      K(ATP) channels in the cortex provide protection from neuronal death. Briefly, in
      vivo focal ischemia (15 min) induced severe neurological deficits and large
      cortical infarcts in Kir6.2(-/-) mice, but not in wildtype mice. Imaging analyses
      of cortical slices exposed briefly to oxygen and glucose deprivation (OGD)
      revealed a substantial number of damaged cells (propidium iodide-labeled) in the
      Kir6.2(-/-) OGD group, but few degenerating neurons in the wildtype OGD group, or
      in the wildtype and Kir6.2(-/-) control groups. Slices from the three control
      groups had far more surviving cells (anti-NeuN antibody-labeled) than slices from
      the Kir6.2(-/-) OGD group. These findings suggest that stimulation of endogenous
      cortical K(ATP) channels may provide a useful strategy for limiting the damage
      that results from cerebral ischemic stroke.

PMID- 17175113
TI  - The association of behavioural and emotional problems with tobacco use in
      adolescence.
AB  - Smoking is a highly addictive behaviour, often initiated during adolescence. It
      is suggested that smoking is associated with behavioural and emotional problems.
      This study aims to assess the impact of psychosocial problems on smoking
      initiation and vice versa. METHOD: We obtained data on self-reported psychosocial
      problems and smoking of adolescents at the age of 13 years and 2 years later. The
      baseline questionnaire was completed by 1789 students. 68% of the baseline
      questionnaire could be linked to a questionnaire of the second measurement.
      RESULTS: 15% smoked at baseline and 29% two years later. Respectively 8% and 9%
      had a clinical Externalizing problem score or a clinical Internalizing problem
      score at baseline, 14% had these problems two years later. Externalizing problems
      at baseline predicted the onset of smoking two years later. Internalizing
      problems only predicted smoking among girls. This association between
      psychosocial problems and smoking is most obvious for the onset of regularly
      smoking and less for the onset of experimenting. Reversibly smoking at baseline
      is only associated with the onset of externalizing problems two years later.
      CONCLUSION: Clinical Externalizing and Internalizing problems make the initiation
      of regular smoking more likely. The effects on experimental smoking are less
      obvious.

PMID- 17175114
TI  - Validation of the Dimensions of Tobacco Dependence Scale for adolescents.
AB  - The purpose of this study was to refine the Dimensions of Tobacco Dependence
      Scale (DTDS) - a measure of tobacco dependence for adolescents - by removing
      poorly discriminating items, testing the measurement structure of the remaining
      items and examining the predictive utility of the resulting scale in terms of its
      ability to explain the average number of cigarettes smoked per day (CPD). A total
      of 1425 current smokers (mean age 16 years) completed the questionnaire.
      Confirmatory factor analyses of the DTDS items supported a 4-factor model
      composed of social, emotional, nicotine and sensory related dimensions of tobacco
      dependence. Predictive utility and incremental validity of the DTDS was evident
      in the many sizable correlations between the DTDS and CPD as well as measures of
      self-rated addiction after controlling for scores on several other commonly used
      measures of nicotine dependence. The results indicate that the DTDS is a reliable
      and valid measure of tobacco dependence for adolescents that has the potential to
      enhance our understanding of the complex processes driving the emergence of
      tobacco dependence and cigarette smoking.

PMID- 17175116
TI  - External beam radiotherapy as postoperative treatment of diffuse pigmented
      villonodular synovitis.
AB  - PURPOSE: Diffuse pigmented villonodular synovitis is a rare proliferative
      disorder of synovial membranes with invasive and expansive growth patterns.
      Radical synovectomy is regarded as the treatment of choice. However, because of
      the high recurrence rates, additive treatment might be useful. Radiotherapy (RT)
      has been evaluated with positive results, but the optimal treatment schedules are
      vague. We have reviewed our experience with postoperative RT in cases of
      suspected or proven residual disease. METHODS AND MATERIALS: Between December
      1996 and January 2006, 7 diffuse pigmented villonodular synovitis patients
      underwent RT at our institution. The most common location was the knee joint (5
      patients). All patients underwent radical surgery and were treated subsequently
      with 6-MV photon RT. The total doses applied were 30-50 Gy, depending on the
      resection status and estimated risk of relapse. For analysis, we retrospectively
      reviewed all patients in April 2006. RESULTS: The mean follow-up time was 29
      months (range, 3-112 months). RT had no acute adverse effects. At the assessment,
      no evidence was found of recurrent or persisting disease in any patient. Of the 7
      patients, 6 reported asymptomatic limb function and excellent quality of life; 1
      patient had persistent restriction of joint movement after repeated surgery. No
      radiotherapeutic late effects were seen. CONCLUSION: The results of our series
      have confirmed the efficacy and safety of postoperative RT for diffuse pigmented
      villonodular synovitis. Hence, this treatment should be considered for patients
      with suspected or proven residual disease.

PMID- 17175115
TI  - Efficacy of complete decongestive therapy and manual lymphatic drainage on
      treatment-related lymphedema in breast cancer.
AB  - OBJECTIVE: To evaluate the results of combined decongestive therapy and manual
      lymphatic drainage in patients with breast cancer-related lymphedema. METHODS AND
      MATERIALS: The data from 250 patients were reviewed. The pre- and posttreatment
      volumetric measurements were compared, and the correlation with age, body mass
      index, and type of surgery, chemotherapy, and radiotherapy was determined. The
      Spearman correlation coefficients and Wilcoxon two-sample test were used for
      statistical analysis. RESULTS: Of the 250 patients, 138 were included in the
      final analysis. The mean age at presentation was 54.3 years. Patients were
      stratified on the basis of the treatment modality used for breast cancer
      management. Lymphedema was managed with combined decongestive therapy in 55%,
      manual lymphatic drainage alone in 32%, and the home program in 13%. The mean
      pretreatment volume of the affected and normal arms was 2929 and 2531 mL. At the
      end of 1 year, the posttreatment volume of the affected arm was 2741 mL. The
      absolute volume of the affected arm was reduced by a mean of 188 mL (p < 0.0001).
      The type of surgery (p = 0.0142), age (p = 0.0354), and body mass index (p <
      0.0001) were related to the severity of lymphedema. CONCLUSION: Combined
      decongestive therapy and manual lymphatic drainage with exercises were associated
      with a significant reduction in the lymphedema volume.

PMID- 17175117
TI  - Specific telomere dysfunction induced by GRN163L increases radiation sensitivity
      in breast cancer cells.
AB  - PURPOSE: Telomerase is expressed in 80-90% of tumor cells, but is absent in most
      somatic cells. The absence of telomerase activity results in progressive telomere
      shortening, leading to cellular senescence or death through deoxyribonucleic acid
      (DNA) damage signals. In addition, a role for telomerase in DNA damage repair has
      also been suggested. A specific telomerase inhibitor, GRN163L that is
      complementary to the template region of the telomerase ribonucleic acid component
      (hTR). We hypothesized that exposure to GRN163L, either through immediate
      inhibition of telomerase activity or through eventual telomere shortening and
      dysfunction, may enhance radiation sensitivity. Our goal was to test whether the
      treatment with GRN163L enhances sensitivity to irradiation (IR) in MDA-MB-231
      breast cancer cells. METHODS AND MATERIALS: The MDA-MB-231 breast cancer cells
      were treated with or without GRN163L for 2-42 days. Inhibition of telomerase
      activity and shortening of telomeres were confirmed. Cells were then irradiated
      and clonogenic assays were performed to show cell survival differences. In vivo
      studies using MDA-MB-231 xenografts were performed to corroborate the in vitro
      results. RESULTS: We show that cells with shortened telomeres due to GRN163L
      enhance the effect on IR reducing survival by an additional 30% (p < 0.01). These
      results are confirmed in vivo, with a significant decrease in tumor growth in
      mice exposed to GRN163L. CONCLUSIONS: We found that GRN163L is a promising
      adjuvant treatment in combination with radiation therapy that may improve the
      therapeutic index by enhancing the radiation sensitivity. These studies prompt
      further investigation as to whether this combination can be applied to other
      cancers and the clinic.

PMID- 17175118
TI  - Changes in salivary gland function after radiotherapy of head and neck tumors
      measured by quantitative pertechnetate scintigraphy: comparison of intensity
      modulated radiotherapy and conventional radiation therapy with and without
      Amifostine.
AB  - PURPOSE: The aim of this study was to compare changes in salivary gland function
      after intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (RT),
      with or without Amifostine, for tumors of the head-and-neck region using
      quantitative salivary gland scintigraphy (QSGS). METHODS AND MATERIALS: A total
      of 75 patients received pre- and post-therapeutic QSGS to quantify the salivary
      gland function. In all, 251 salivary glands were independently evaluated. Changes
      in the maximum uptake (DeltaU) and relative excretion rate (DeltaF) both pre- and
      post-RT were determined to characterize radiation-induced changes in the salivary
      gland function. In addition, dose-response curves were calculated. RESULTS: In
      all groups, maximum uptake and relative excretion rate were reduced after RT
      (DeltaU <or=0 and DeltaF <or=0). The reduction was significantly lower for IMRT
      than for conventional RT. For the parotid glands, the reduction was smaller for
      the IMRT-low than for the IMRT-high group. For the Amifostine-high and the
      conventional group the difference was significant only for one parameter (DeltaU,
      parotid and submandibular glands, p < 0.05). In contrast to this, the difference
      between the Amifostine-low and the conventional group was always significant or
      at least showed a clear trend for both changes in U and F. In regard to the
      endpoint "reduction of the salivary gland excretion rate of more than 50%," the
      dose-response curves yielded D50-values of 34.2 +/- 12.2 Gy for the
      conventionally treated group and 36.8 +/- 2.9 Gy for the IMRT group. For the
      Amifostine group, an increased D50-values of 46.3 +/- 2.3 Gy was obtained.
      CONCLUSION: Intensity-modulated RT can significantly reduce the loss of parotid
      gland function when respecting a certain dose threshold. Conventional RT plus
      Amifostine prevents reduced salivary gland function only in the patient group
      treated with <40.6 Gy.

PMID- 17175119
TI  - Measuring the stability of illicit drug markets: why does it matter?
AB  - Contemporary drug policy in the United States favors a balanced approach
      including a supply side dimension. The supply side dimension is grounded in the
      assumption that the disruption of illicit drug markets will result in diminished
      capacity of the markets to provide for consumer demand and thereby a reduction in
      the use of illicit drugs and a related increase in demand for treatment. In this
      paper we consider the disruption of methamphetamine markets in 10 cities in terms
      of the relative stability of those markets. We use data from the Arrestee Drug
      Abuse Monitoring (ADAM) program for the years 2000-2003. We conduct a comparative
      analysis of those markets and look at patterns of methamphetamine use and
      participation in treatment in those cities. Our findings demonstrate how it is
      possible to construct measures of market stability, and how to use those measures
      to assess the stability of illicit drug markets in terms of both relative value
      and in fluctuation over time. We also demonstrate that markets with different
      patterns of stability will exhibit different patterns of drug using and treatment
      participation. We conclude that understanding patterns of market stability will
      help us to understand and respond to patterns of drug using and treatment
      participation.

PMID- 17175120
TI  - Comparative and phylogenetic analysis of alpha-L-fucosidase genes.
AB  - Fucosylated glycoconjugates play a role in a wide variety of biological
      processes, including immune responses, signal transduction, ontogenic events and
      pathogenesis of several human diseases. Alpha-L-fucosidases, which are
      responsible for their processing, have been demonstrated to be involved in
      lysosomal storage disease, inflammation, cystic fibrosis, cancer development and
      in the interactions between gametes in vertebrates as well as invertebrates. The
      sequence and comparative genomic analysis of these glycosyl hydrolases and the
      study of their evolutionary relationships appear therefore to be of considerable
      interest. In this work we carried out extensive similarity searches and
      comparative analyses to identify sequences encoding alpha-L-fucosidases. We have
      identified novel alpha-L-fucosidase coding sequences in worms, insects, sea
      urchin, ascidians, fish, chicken, amphibians, mammals and various bacteria
      resulting in a total of 39 alpha-L-fucosidase sequences. Two alpha-L-fucosidases
      that are present in all vertebrates likely reflect a distinct biological role for
      paralogous genes. Comparative sequence analysis of all metazoan alpha-L
      fucosidases reveals a broad conservation of features, including the aspartate
      residue that constitutes the catalytic nucleophile. However, a cysteine which is
      thought to be part of the active site is also conserved in metazoa but not in
      arthropods, where it is replaced by an alanine. Phylogenetic analysis suggests a
      gene duplication event very early in metazoan evolution with the subsequent
      differential loss of isoforms in various metazoan lineages.

PMID- 17175122
TI  - Cell-surface streptavidin fusion protein for rapid selection of transfected
      mammalian cells.
AB  - We developed a series of eight mammalian cell surface marker fusion genes by
      using the streptavidin gene from Streptomyces avidinii. These fusion genes are
      useful and non-growth-toxic selection markers for rapid-harvest transfected
      mammalian cells. Two streptavidin constructs were used; the longer fragment
      contains the native bacterial signal sequence, which the shorter fragment lacks.
      For expression of the streptavidin antigen on the surface of mammalian cells,
      streptavidin was flanked by a mammalian signal sequence and a transmembrane
      domain (from mouse H2-K or Kit); some constructs also contained the gene for
      enhanced green fluorescent protein (EGFP). We transfected a series of plasmids
      encoding the fusion proteins into HeLa cells and determined that the transfected
      cells produced the fusion protein on their cell surfaces. To separate transfected
      cells from nontransfected cells, we incubated cells with a polyclonal antibody
      against streptavidin, and antibody-bound cells were harvested by the use of
      paramagnetic beads coupled with the corresponding secondary antibody. We obtained
      highly pure populations of transfected cells; this result also confirmed the
      production of the fusion protein on the cell surface. Cell growth assays revealed
      that none of the transfected fusion genes or their products adversely affected
      the proliferation of HeLa cells. Our results indicate that the fusion constructs
      we developed and the immunomagnetic separation protocol we used are valuable
      tools for various transfection applications. In particular, the constructs
      containing EGFP are advantageous because transfection efficiency can be assessed
      without additional treatment of cells.

PMID- 17175121
TI  - Molecular cloning and initial characterization of African green monkey
      (Cercopithecus aethiops) corticotropin releasing factor receptor type 1 (CRF1)
      from COS-7 cells.
AB  - We report the expression of endogenous CRF1 in COS-7 cells (African green monkey
      origin). Cloning of the coding region of CRF1 gene identified three alternatively
      spliced isoforms with nucleotide and predicted amino acid sequences corresponding
      to the membrane bound alpha and c and soluble e isoforms. DNA sequencing of the
      main isoform CRF1alpha showed homologies of 99%, 97% and 91% with the rhesus
      monkey, human and rodent genes, respectively; the deduced protein sequence
      differed in only one amino acid with rhesus monkey and human. Western blot
      analysis with antibodies against human CRF1 demonstrated immunoreactive proteins
      with MW of 37, 52, 70 and 80-85 in crude membrane or cytoplasm preparation; two
      additional species of 40 and 60 kDa were detected only in the cytoplasmic
      fraction. On immunocytochemistry CRF1 was localized to both the cell surface and
      intracellularly. The receptor was functional, e.g., addition of CRF to COS-7
      cells inhibited cell proliferation and stimulated release of arachidonic acid;
      nevertheless, it was poorly coupled to cAMP production (its stimulation was
      minimal in native cells). In conclusion, COS cells that are routinely used for
      the study of transfected CRF receptors do express endogenous CRF1 mRNA with
      splicing behavior similar to that reported in human and rodent cells, and
      translated into functional CRF1 receptors.

PMID- 17175123
TI  - The usefulness of the bioconcentration factor as a tool for priority setting in
      chemicals control.
AB  - The implementation of the REACH system will lead to the creation of a single,
      uniform legislation for industrial chemicals in Europe. An important aim of this
      legislation is to generate toxicity data for previously untested chemicals.
      Testing tens of thousands of chemicals can however not be done in one step, and
      criteria for priority setting is therefore an essential part of the proposed
      REACH system. In this study we investigate potential consequences of using
      bioaccumulation (B) data as a tool for priority setting in chemicals control. The
      results of this investigation suggests that the use of data for the
      bioconcentration factor (BCF, as an estimation of B) at first tier will not
      introduce bias towards a particular type of toxicity (i.e. carcinogenicity,
      reproductive toxicity or mutagenicity) in the priority setting process.

PMID- 17175125
TI  - Factors influencing the contamination of UK banknotes with drugs of abuse.
AB  - Bank of England banknotes sampled from different locations in the UK have been
      analysed for the presence of cocaine, diamorphine (DAM), Delta(9)
      tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA). A
      database of the contamination detected is routinely used as a benchmark against
      which the contamination detected on seized banknotes can be compared. Evidence
      presented at court details how banknotes seized from a suspect may differ from
      banknotes in general circulation in terms of their contamination with controlled
      drugs. A question arising from such evidence is whether seized banknotes could
      have become contaminated through being in circulation in drug "hot spots". In
      order to address this issue, a Plackett-Burman experimental design was used to
      investigate the influence of source location and other factors on banknote
      contamination with drugs of abuse. Banknotes were drawn from banks in eight
      regions throughout the UK. Each location could be described by a unique
      combination of the factors under investigation, namely whether the location was
      rural or urban, in the North or South of the UK, and whether it was a port of
      entry. The socio-economic class and the proportion of drug offenders in the area
      and the denomination of the banknotes were also considered as potentially
      influential factors. Indices were calculated to describe the degree to which
      samples were contaminated with different drugs, and normal probability plots were
      used to identify the factors that could account for the contamination observed.
      Whilst some factors were more influential than others, it was shown that, at the
      95% confidence level, none of the proposed factors were significant influences on
      the contamination. Cocaine contamination on banknotes has been shown to follow a
      log-normal distribution. It was, therefore, possible to calculate F- and t
      statistics to compare the cocaine contamination on the entire sample set with
      that detected on a second sample set consisting of banknotes all drawn from a
      single bank branch. It was shown that both inter-bank samples and intra-bank
      samples had similar variance and similar contamination levels at the 95%
      confidence level. This suggests that there are no significant regional trends in
      the contamination of banknotes with drugs of abuse across the UK.

PMID- 17175126
TI  - Appropriate use of polymerase chain reaction for detection of herpes simplex
      virus 2 in cerebrospinal fluid of patients at an inner-city hospital.
AB  - Polymerase chain reaction (PCR) tests that detect herpes simplex virus (HSV) DNA
      in cerebrospinal fluid (CSF) are increasingly used to diagnose central nervous
      system (CNS) infections caused by HSV. To determine proper utilization of this
      test at an inner-city hospital, we performed a case-control study of adult
      patients, with HSV detected in CSF by PCR. Retrospective review of
      characteristics of adult patients hospitalized between 1997 and 2000 with CSF
      positive for HSV was done and compared to control patients with suspected CNS
      infection and negative CSF PCR. CSF from 1174 patients was tested; 20 (1.7%) had
      HSV DNA detected, 19/20 were HSV-2 and 1 was HSV-1. The HSV-2 cases were females
      (74%), with a median age of 41 years, of African-American ethnicity (100%). Of
      the cases, 90% had acute aseptic meningitis versus 13% controls (P < .001).
      Recurrent meningitis occurred in 42% cases and 3% controls (P < .001). CSF
      parameters significantly associated with HSV-2 positivity was lymphocytic
      pleocytosis (median leukocyte, 475 cell/mm3, 90% lymphocytes) (P < .001). In
      conclusion, HSV-1 was rarely detected in CSF of patients with suspected CNS
      infection. HSV-2 is more frequent, predominantly in young African-American women
      with lymphocytic aseptic meningitis, and is often recurrent. PCR testing for HSV
      2 in CSF at inner-city hospitals can be greatly reduced by the application of
      these parameters.

PMID- 17175124
TI  - Genetic dependence of cochlear cells and structures injured by noise.
AB  - The acute and permanent effects of a single damaging noise exposure were compared
      in CBA/J, C57BL/6 (B6), and closely related strains of mice. Two hours of
      broadband noise (4-45 kHz) at 110 dB SPL led to temporary reduction in the
      endocochlear potential (EP) of CBA/J and CBA/CaJ (CBA) mice and acute cellular
      changes in cochlear stria vascularis and spiral ligament. For the same exposure,
      B6 mice showed no EP reduction and little of the pathology seen in CBA. Eight
      weeks after exposure, all mice showed a normal EP, but only CBA mice showed
      injury and cell loss in cochlear lateral wall, despite the fact that B6 sustained
      larger permanent threshold shifts. Examination of noise injury in B6 congenics
      carrying alternate alleles of genes encoding otocadherin (Cdh23), agouti protein,
      and tyrosinase (albinism) indicated that none of these loci can account for the
      strain differences observed. Examination of CBA x B6 F1 mice and N2 backcross
      mice to B6 further indicated that susceptibility to noise-related EP reduction
      and associated cell pathology are inherited in an autosomal dominant manner, and
      are established by one or a few large effect quantitative trait loci. Findings
      support a common genetic basis for an entire constellation of noise-related
      cochlear pathologies in cochlear lateral wall and spiral limbus. Even within
      species, cellular targets of acute and permanent cochlear noise injury may vary
      with genetic makeup.

PMID- 17175127
TI  - Palliation for suspected unresectable hilar cholangiocarcinoma.
AB  - AIM: The aim of this study was to evaluate the outcome of different techniques of
      palliation for patients with hilar cholangiocarcinoma. METHOD: All patients
      treated with palliative intent between 1988 and 2004 at the Royal Infirmary of
      Edinburgh were reviewed. Patients were analysed on an intention to treat basis.
      Demographics, procedure and outcome (including re-admissions) were recorded.
      RESULTS: Two hundred and thirty-three patients underwent palliative treatment for
      suspected hilar cholangiocarcinoma. The diagnosis was confirmed histologically in
      109 patients. The procedure related morbidity and mortality was 54/225 and 18/207
      respectively. Seventy-one patients required re-admission. Twenty patients
      underwent surgical biliary bypass for jaundice. Those undergoing surgical
      palliation had a longer median (95% CI) time to re-admission (16 (0-36) vs.7 (2
      12) weeks, p=0.001). Endoscopic retrograde cholangio-pancreatography (ERCP) and
      stenting was only successful in 28 patients and was associated with a
      significantly higher re-admission rate compared to patients in whom ERCP was not
      performed (60/179 vs. 4/27, p=0.050). The overall median (95% CI) survival was
      145 (124-185) days. CONCLUSION: Current options for palliation of hilar
      cholangiocarcinoma provide good short term success but are all associated with
      significant early and late morbidity. Due to its low success and association with
      an increased re-admission rate, ERCP for definitive palliation should not be used
      in the first line staging and management of these patients.

PMID- 17175128
TI  - Prevention of intrahepatic recurrence by adjuvant (131)iodine-labeled lipiodol
      after resection for hepatocellular carcinoma in HCV-related cirrhosis.
AB  - AIM: To evaluate the impact of postoperative injection into the hepatic artery of
      131-iodine-labeled lipiodol on disease-free and overall survival rates in
      patients who underwent liver surgical resection for hepatocellular carcinoma.
      METHODS: Ten consecutive patients with HCV (hepatitis C virus)-related cirrhosis
      who underwent liver surgical resection for hepatocellular carcinoma were treated
      with adjuvant injection of 131-iodine-labeled lipiodol. They were matched with 20
      HCV-positive cirrhotic controls who underwent liver resection alone; patients
      were paired in terms of age, Child-Pugh class, tumor size, microscopic vascular
      invasion, tumor histological pattern, presence of satellite nodules and type of
      surgical resection. Recurrence was defined as the development of a new
      hypervascularizated nodule in the liver. RESULTS: No significant differences were
      found between the two groups in clinical, biologic and histologic
      characteristics, except a lower platelet count in the control group. None of the
      treated patients developed an intrahepatic recurrence until the 15th month from
      liver resection, whereas recurrences occurred in nine of the 20 patients in the
      control group (p=0.01). From 18 months onwards, recurrences appeared also in the
      treated patients, and after 36 months of follow-up both recurrence rate and
      overall survival were not significantly different between the two groups.
      CONCLUSIONS: Intrahepatic injection of 131-iodine-labeled lipiodol improves the
      disease-free survival rate following liver resection of hepatocellular carcinoma
      in the short term up to 15 months; this advantage fades, however, away after 36
      months.

PMID- 17175129
TI  - Implementation of a map in radical prostatectomy specimen allows visual
      estimation of tumor volume.
AB  - INTRODUCTION: Tumor volume is one of the best documented prognostic factors for
      prostate cancer. There are several methods to gain this important parameter but
      unfortunately most of the clinicians in the world do not get this information in
      their routine practice from the pathologist. We developed a standardized method
      to handle radical prostatectomy specimens including a special form of mapping in
      order to document relevant morphological data. The aim of this study was to
      investigate if our model of mapping prostate cancer, which we use in routine
      practice, may serve for visual estimation of tumor volume. METHODS: We estimated
      the tumor volume of prostate cancer by visual estimation of 350 maps of radical
      prostatectomy specimens and correlated these data with established prognostic
      parameters and clinical outcome. RESULTS: Significant correlations between tumor
      volumes, as obtained from our mapping, and known prognostic parameters such as
      preoperative serum levels of prostatic specific antigen, loss of differentiation,
      histological grade, lymph node metastasis, and margins were found. In a
      multivariate analysis, only Gleason score and tumor stage were shown to be
      independent prognostic parameters. DISCUSSION: We demonstrate that mapping of
      prostate cancer is more than a simple method of documentation but may serve as a
      method for visual estimation of tumor volume of prostate cancer after radical
      prostatectomy. This method can further be used for a visual documentation of the
      tumor stage independent of changes in the TNM classification. The method is
      inexpensive and practicable and can therefore be applied in routine surgical
      pathology.

PMID- 17175130
TI  - A systematic review on the significance of extracapsular lymph node involvement
      in gastrointestinal malignancies.
AB  - AIMS: The impact of extracapsular lymph node involvement (LNI) has been studied
      for several malignancies, including gastrointestinal malignancies. Aim of this
      study was to assess the current evidence on extracapsular LNI as a prognostic
      factor for recurrence in gastrointestinal malignancies. METHODS: The Cochrane
      Database of systematic reviews, the Cochrane central register of controlled
      trials, and MEDLINE databases were searched using a combination of keywords
      relating to extracapsular LNI in gastrointestinal malignancies. Primary outcome
      parameters were incidence of extracapsular LNI and overall five-year survival
      rates. FINDINGS: Fourteen manuscripts were included, concerning seven
      oesophageal, three gastric, one colorectal, and three rectal cancer series with a
      total of 1528 node positive patients. The pooled incidence of extracapsular LNI
      was 57% (95% CI: 53-61%) for oesophageal cancer, 41% (95% CI: 36-47%) for gastric
      cancer, and 35% (95% CI: 31-40%) for rectal cancer. In nine of the 14 studies a
      multivariate analysis was performed. In eight of these nine studies extracapsular
      LNI was identified as an independent risk factor for recurrence. CONCLUSION:
      Extracapsular LNI is a common phenomenon in patients with gastrointestinal
      malignancies. It identifies a subgroup of patients with a significantly worse
      long-term survival. This systematic review highlights the importance of assessing
      extracapsular LNI as a valuable prognostic factor. Pathologists and clinicians
      should be aware of this important feature.

PMID- 17175131
TI  - Synthesis of 3-(2-pyridyl)-2-substituted-quinazolin-4(3H)-ones as new analgesic
      and anti-inflammatory agents.
AB  - A new series of 3-(2-pyridyl)-2-substituted-quinazolin-4(3H)-ones were
      synthesized by reacting the amino group of 2-hydrazino-3-(2-pyridyl)-quinazolin
      4(3H)-one with a variety of aldehydes and ketones. The starting material 2
      hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one was synthesized from 2
      aminopyridine. The title compounds were investigated for analgesic, anti
      inflammatory and ulcerogenic index activities. While the test compounds exhibited
      significant activity, compound 2-(1-ethylpropylidene)-hydrazino-3-(2-pyridyl)
      quinazolin-4(3H)-one (AS2) showed moderate analgesic activity and compound 2-(1
      methylbutylidene)-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one (AS3) showed
      realistic anti-inflammatory activity when compared to the reference standard
      diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic
      side effect when compared to aspirin.

PMID- 17175132
TI  - Evaluation of the barrier properties of a commercially available renal epithelial
      cell system.

PMID- 17175133
TI  - Should the retention trial of the Test of Memory Malingering be optional? A
      reply.

PMID- 17175135
TI  - A two-generation reproductive toxicity study of decamethylcyclopentasiloxane (D5)
      in rats exposed by whole-body vapor inhalation.
AB  - This two-generation reproduction study assessed the reproductive hazard potential
      of decamethylcyclopentasiloxane (D(5)). Sprague-Dawley rats (30/sex/group) were
      exposed by whole-body vapor inhalation to a target concentration of 30, 70, or
      160 ppm D(5) or filtered air for 6h/day. Exposures for the F(0) and F(1)
      generations started at least 70 days prior to mating and lasted through weaning
      of the respective pups on postnatal day (PND) 21. Female exposures were
      interrupted from gestation day (GD) 21 through PND 4 to allow for parturition and
      to permit continuous maternal care for the early neonates. F(2) pups were not
      directly exposed to D(5). There were no exposure-related mortalities, clinical
      signs of toxicity, or effects on body weight or food consumption. There were no
      treatment-related gross findings or organ weight effects at the F(0) and F(1)
      necropsies. Other than minimal alveolar histiocytosis in all exposed groups,
      there were no noteworthy microscopic findings. Reproductive parameters (number of
      days between pairing and mating, mating and fertility indices, gestation length,
      and parturition), spermatogenic parameters and ovarian primordial follicle counts
      and numbers of corpora lutea in the F(0) and F(1) parental animals were not
      significantly changed between treated and control groups. Mean live litter sizes,
      number of pups born, sex ratios, pup body weights, postnatal pup survival and
      general physical condition of offspring in each generation were not affected. The
      slight, but statistically significant, increase in the mean F(1) male pup AGD in
      the 160 ppm group was not considered to be related to treatment. Vaginal patency
      and balanopreputial separation were unchanged compared to controls. Thus, the No
      Observed-Adverse-Effect-Level (NOAEL) for parental and reproductive toxicity was
      determined to be 160 ppm D(5).

PMID- 17175136
TI  - Repeated inhalation of toluene by rats performing a signal detection task leads
      to behavioral tolerance on some performance measures.
AB  - Previous work showed that trichloroethylene (TCE) impairs sustained attention as
      evidenced by a reduction in accuracy and elevation of response latencies in rats
      trained to perform a visual signal detection task (SDT). This work also showed
      that these effects abate during repeated exposures if rats inhale TCE while
      performing the SDT. The present experiment sought to determine whether toluene,
      another commonly-used solvent, would induce tolerance similarly if inhaled
      repeatedly during SDT testing. Sixteen male, Long-Evans rats were trained to
      perform the SDT. Upon completion of training, rats were divided into 2 groups. In
      Phase I, concentration-effect functions were determined for toluene (0, 1200,
      1600, 2000, 2400 ppm) in both groups. Toluene reduced the proportion of correct
      responses [P(correct)], and increased response time (RT) and response failures.
      In Phase II, Group-Tol inhaled 1600 ppm toluene while Group-Air inhaled clean air
      during 11 daily SDT sessions. In Group-Tol the effect of toluene on P(correct)
      abated after 3 days, while RT remained elevated for the duration of the repeated
      exposures. In Phase III, toluene concentration-effect functions were re
      determined for both groups. Group-Air remained impaired on all test measures,
      whereas for Group-Tol, toluene did not reduce P(correct), but continued to
      increase RT. These data confirm our previous hypothesis that animals can develop
      tolerance to chemical exposures that impair appetitively-motivated behaviors if
      that impairment leads to loss of reinforcement.

PMID- 17175137
TI  - Murine macrophage P2X7 receptors support rapid prothrombotic responses.
AB  - Non-apoptotic externalization of phosphatidylserine (PS) can act as a reactive
      surface for the efficient assembly of the prothrombinase complex leading to
      thrombin generation and coagulation. Here we show that extracellular ATP, acting
      at the macrophage P2X(7) receptor, drives the rapid Ca(2+)-dependent formation
      and release of PS-rich microvesicles that enhance the assembly of the
      prothrombinase complex and subsequent formation of thrombin. Incubation with
      P2X(7) receptor antagonists (KN-62 and Brilliant Blue G) attenuates ATP induced
      prothrombotic responses. Consistent with the hypothesis that exposed PS enhances
      prothrombinase activity; pre-incubation with annexin V blocks the increase in
      thrombin formation. The rapid translocation of PS and formation of pro-thrombotic
      microvesicles occurs in the absence of cell lysis. These data demonstrate that
      the pro-inflammatory P2X(7) receptor can also support and propagate rapid
      increases in thrombin formation.

PMID- 17175134
TI  - Norman Cousins Lecture. Glia as the "bad guys": implications for improving
      clinical pain control and the clinical utility of opioids.
AB  - Within the past decade, there has been increasing recognition that glia are far
      more than simply "housekeepers" for neurons. This review explores two recently
      recognized roles of glia (microglia and astrocytes) in: (a) creating and
      maintaining enhanced pain states such as neuropathic pain, and (b) compromising
      the efficacy of morphine and other opioids for pain control. While glia have
      little-to-no role in pain under basal conditions, pain is amplified when glia
      become activated, inducing the release of proinflammatory products, especially
      proinflammatory cytokines. How glia are triggered to become activated is a key
      issue, and appears to involve a number of neuron-to-glia signals including
      neuronal chemokines, neurotransmitters, and substances released by damaged, dying
      and dead neurons. In addition, glia become increasingly activated in response to
      repeated administration of opioids. Products of activated glia increase neuronal
      excitability via numerous mechanisms, including direct receptor-mediated actions,
      upregulation of excitatory amino acid receptor function, downregulation of GABA
      receptor function, and so on. These downstream effects of glial activation
      amplify pain, suppress acute opioid analgesia, contribute to the apparent loss of
      opioid analgesia upon repeated opioid administration (tolerance), and contribute
      to the development of opioid dependence. The potential implications of such glial
      regulation of pain and opioid actions are vast, suggestive that targeting glia
      and their proinflammatory products may provide a novel and effective therapy for
      controlling clinical pain syndromes and increasing the clinical utility of
      analgesic drugs.

PMID- 17175138
TI  - Deficits in cue detection and intention retrieval underlie prospective memory
      impairment in schizophrenia.
AB  - Emerging evidence indicates that individuals with schizophrenia (SCZ) may exhibit
      deficits in prospective memory (ProM), a dissociable and ecologically important
      aspect of episodic memory entailing the formation, maintenance, and execution of
      future intentions. The present study aimed to elucidate the component processes
      of ProM impairment in 41 individuals with SCZ relative to 41 demographically
      similar healthy comparison (HC) participants. Results revealed that the SCZ group
      performed worse than HCs on overall ProM, with comparable deficits on time- and
      event-based ProM trials. In the SCZ cohort, better ProM performance was
      associated with younger age and less severe negative symptoms. Although a
      significantly greater number of Task Substitution and Loss of Time errors were
      evident in the SCZ group as compared to HCs, the most prevalent error type in SCZ
      was characterized by a complete failure to respond to the ProM cue. Importantly,
      the SCZ and HC groups did not differ on a post-test multiple-choice recognition
      trial, suggesting adequate formation and maintenance (i.e., retention) of the
      ProM cue-intention pairing when self-directed monitoring and retrieval demands
      were minimized. Findings indicate that SCZ is associated with impairment in the
      cue detection and self-initiated retrieval components of executing future
      intentions, which is consistent with a possible prefrontostriatal loop
      neuropathogenesis. Further studies are needed to explore the neurobiological
      mechanisms of SCZ-associated ProM impairment and the impact of such deficits on
      daily functioning (e.g., medication compliance).

PMID- 17175139
TI  - Junctional basement membrane anomalies of skin and mucosa in lipoid proteinosis
      (hyalinosis cutis et mucosae).
AB  - BACKGROUND: Excessive basement membrane (BM) deposition in skin and mucosa is
      characteristic for lipoid proteinosis (LP; hyalinosis cutis et mucosae), an
      inherited disease caused by extracellular matrix protein 1 (ECM1) mutations.
      According to ultrastructure there are striking differences between junctional and
      microvascular BM. OBJECTIVE: Distinct analysis of the junctional zone in
      epidermis and oral mucosa, contrasting concentric BM arrays in the
      microvasculature; evaluation of impact on epithelial histogenesis and
      differentiation, and specifically on adhesion structures to BM (hemidesmosomes).
      METHODS: LP-epithelia were analyzed for alterations in differentiation, BM
      composition and texture, and hemidesmosomal components by indirect
      immunofluorescence (IIF), electron microscopy (EM), and immunoelectron microscopy
      (ImEM). RESULTS: Most striking was the irregular deposition of collagen IV and
      VII, BM-laminin, and laminin-5 at the junctional zone, accompanied by lamellate
      or punctuated structures below BM (IIF), whereas integrin alpha6beta4 and bullous
      pemphigoid antigen-1 and -2 (BPAG-1/-2) were regularly aligned. Also integrins
      alpha2beta1 and alpha3beta1 remained restricted to the epidermal basal layer,
      while the tissue-specific differentiation markers keratin K1/10 (mucosa,
      additionally K4/13) appeared delayed indicating mild hyperplasia, further
      confirmed by focal K6/16 expression. Ultrastructure (EM) disclosed abundance of
      extended basal cell protrusions and junctional aberrations like exfoliating
      excessive BM material. Hemidesmosomes were complete, but ImEM indicated weakened
      interactions between their components (BPAG-1, -2, and HD1). Confirming IIF,
      collagen IV and VII, and laminin-5 appeared extensively scattered, the latter two
      probably remaining associated. CONCLUSIONS: Subtle defects in anchorage assembly,
      spanning the entire BM zone, apparently compromise epithelial-matrix adhesion,
      which may provoke (mechanical stress-induced) erroneous BM repair.

PMID- 17175140
TI  - Antifungal resistance in Candida spp. isolated in Italy between 2002 and 2005
      from children and adults.
AB  - The activity of amphotericin B, fluconazole, flucytosine, itraconazole and
      voriconazole was tested in vitro against 618 clinical Candida spp. isolates,
      using the broth microdilution or the disk diffusion method (voriconazole).
      Amphotericin B and voriconazole were the most potent antifungal agents assayed
      (100% of susceptible strains). Resistance to fluconazole and itraconazole was
      detected in three (0.7%) and 11 (2.7%) isolates of Candida albicans and in four
      (3.7%) isolates of Candida glabrata. Flucytosine intermediate, resistant strains,
      or both, were observed in C. albicans (0.3% and 0.7%), C. glabrata (2.8%
      intermediate) and C. tropicalis (15.2% and 15.2%). C. krusei was the least
      susceptible species to azoles. No statistically significant differences in the
      rates of resistant isolates depending on site of infection and age of the patient
      were observed, with the exception of C. albicans and itraconazole (higher
      percentage of resistance in children). At present, acquired antifungal resistance
      represents an uncommon finding in most Candida spp. circulating in Northern
      Italy.

PMID- 17175141
TI  - Activity of cefditoren against clinical isolates of Streptococcus pneumoniae
      showing non-susceptibility to penicillins, cephalosporins, macrolides, ketolides
      or quinolones.

PMID- 17175143
TI  - [Determinants of diphemanil methylsulfate (Prantal) utilization: a survey of
      practice in the French neonatal and intensive care units].
AB  - Diphemanil methylsulfate (Prantal) is a quaternary ammonium with
      parasympathicolytic properties. It is used in premature and term neonates with
      bradycardias related to vagal hyper reflectivity (HRV). OBJECTIVES: To assess the
      use of Prantal in the French neonatal and intensive care units: its indications,
      its modalities of use, its side effects and the number of patients treated during
      1 year (2004) in France. METHODS: A questionnaire was electronically sent to all
      neonatology units and all neonatal intensive care units in France. RESULTS: Among
      202 units, 121 (60%) answered the questionnaire. Prantal was reported to be used
      in 51 (42.1%) units. Among them, 38 (31.4%) actually treated 169 patients in 2004
      with a mean number of patients treated by unit of 4. The diagnostic of HRV was
      supported by: a history of malaise (84.3%), bradycardia (94.1%), oculocardiac
      reflex (74.5%), cardiac Holter (76.4%), cardiorespirographic recording (19.6%),
      esophageal pHmetry (35.2%) and esophageal fibroscopy (21.5%). The mean starting
      dosing was 4.7 mg/kg/d, the mean maximal dosing was 9 mg/kg/d and the mean daily
      intakes were initially 2.3 and secondary 2.9. Prantal dosing was adjusted to
      weight in 54.9%, every month in 85.7%. Treatment was stopped at the mean post
      natal age of 6 months, mostly in a progressive manner and without monitoring
      help. CONCLUSION: Prantal was seldom used in 2004 in France for different
      reasons: HRV is an uncertain entity, the efficacy of Prantal has not been
      validated and atropinic side effects can be encountered.

PMID- 17175145
TI  - [Premedication before tracheal intubation in French neonatal intensive care units
      and delivery rooms].
AB  - Tracheal intubation is a painful procedure commonly used in the neonatal
      intensive care units and in the delivery rooms. It can be complicated by changes
      in vital signs. OBJECTIVE: To ascertain the use of sedatives and/or analgesics
      before tracheal intubation in French neonatal intensive care units and delivery
      rooms. METHODS: A survey by questionnaire sent to 58 neonatal intensive care
      units and 58 maternities. RESULTS: We obtained 46 responses (79,3%) from the
      neonatal intensive care units and 38 (65,5%) from the delivery rooms. In neonatal
      intensive care units, 74% of the newborns received a sedative and/or an analgesic
      before being intubated, and 60% of the units had specific written guidelines.
      Opioids and benzodiazepines were the main drugs used. In the delivery rooms,
      sedatives or analgesics were only used in 21% of the centres. CONCLUSION: The use
      of sedation-analgesia seems to improve in neonatology but is still insufficient
      in the delivery rooms. The development of specific guidelines and a best learning
      about the different drugs are necessary.

PMID- 17175142
TI  - Effects of risperidone on dopamine receptor subtypes in developing rat brain.
AB  - The atypical antipsychotic risperidone is often prescribed to pediatric patients
      with neuropsychiatric disorders, though its effects on the developing brain
      remain unclear. Accordingly, we studied the effects of repeated treatment of
      risperidone on dopamine receptors in brain regions of juvenile rat. Levels of
      dopamine receptors (D(1), D(2), D(3), D(4)) in forebrain regions of juvenile rats
      were quantified after 3 weeks of treatment with three different doses of
      risperidone (0.3, 1.0 and 3.0 mg/kg) and compared findings to those in adult rats
      treated with risperidone (3.0 mg/kg/day) previously. Risperidone (at 1.0 and 3.0
      mg/kg/day) increased levels of D(1) receptors in nucleus accumbens and caudate
      putamen of juvenile, but not adult rats. Conversely, all three doses of
      risperidone dose-dependently increased D(2) labeling in medial prefrontal cortex
      and hippocampus, and D(4) receptor in nucleus accumbens, caudate-putamen and
      hippocampus of juvenile animals as well as in adults. Only the high dose of
      risperidone (3.0 mg/kg) increased D(2) receptors in caudate-putamen in both
      juvenile and adult brain. D(3) receptors were not altered by risperidone in any
      brain region at any dose or age. The findings indicate dose-dependent effects of
      risperidone on dopamine receptors in developing animals, and that juvenile
      animals are more sensitive than adults to the cerebral effects of risperidone.

PMID- 17175144
TI  - [Low level educated community health workers training: a strategy to improve
      children access to acute respiratory treatment in Senegal].
AB  - BACKGROUND: Acute respiratory infections (ARI) are the leading cause of death in
      childhood. Most of children's deaths happen at home without health level first
      cares. However in Senegal only health workers are allowed to prescribe
      antibiotics. A competency-based training was developed to improve and assess the
      management of acute respiratory infections in young children aged 2 to 59 months
      by low level educated community health workers (CHWs) in 4 districts of Senegal.
      The first findings showed the CHWs capable of acquiring the skills needed to
      effectively manage ARI cases in accordance with the World Health Organization's
      ARI case management strategy. The aim of this study was to assess the quality of
      their management after a 1 year follow-up. METHODS: We provided to CHWs 3 days
      course in ARI management. After the 3-day course, a 4-month follow-up was
      performed. We organized a 1-day refresher course every month and in every
      district. In order to assess the quality of management of CHWs we analyzed the
      management process and compared the CHWs classification to the classification of
      the first level health facilities. RESULTS: Twenty-three percent (3727/15,965) of
      IRA cases of district were managed by CHWs. Ninety percent (2738/3042) among them
      were well classified, well managed and well followed-up. But 28% of severe
      pneumonia cases were misclassified as pneumonia. About treatment, 22.5% of 'cough
      or cold' got wrong treatment with cotrimoxazole and 10.3% of severe pneumonia got
      cotrimoxazole without referral. Less than half of severe pneumonia benefited of
      the first follow-up and only 18% of the second. CONCLUSIONS: The results
      highlight that a CHWs low-level educated in French, trained and followed-up could
      apply the WHO algorithm of IRA management. They could help to give proximal care
      related to children ARI, to the community. But it seems useful of emphasizing the
      recognition of danger signs and the follow-up of severe cases.

PMID- 17175146
TI  - [Adoption in China].

PMID- 17175147
TI  - [Different diagnosis of children with viral or bacterial bronchopneumonia
      infection].
AB  - Community-acquired bronchopneumonia is very common in children and responsible
      for a great morbidity. It can be revealed by bronchiolitis, due to viral
      infection, bronchitis (80% due to viruses), and pneumonia potentially much more
      severe due to bacteria (60%), viruses (40%) or both causes (20%). Being unable to
      exclude a bacterial origin in pneumonia leads physicians to prescribe
      systematically antibiotics.

PMID- 17175148
TI  - Dimethylthetin treatment causes diffuse alveolar lung damage: a pilot study in a
      sheep model of Continuous Ambulatory Peritoneal Dialysis (CAPD).
AB  - Total plasma homocysteine (Hcy) concentration correlates with risk of vascular
      disease. Over 80% of chronic renal failure patients have elevated plasma Hcy and
      a 10-20 times higher incidence of vascular disease. Glycine betaine lowers plasma
      Hcy through methylation catalysed by betaine-homocysteine methyltransferase
      (BHMT). Dimethylthetin (DMT), a synthetic glycine betaine analogue, is a more
      effective BHMT substrate. DMT is therefore a potential therapeutic agent for
      reducing plasma Hcy in humans and may be particularly useful in renal failure
      patients receiving dialysis because of chronic betaine depletion as a result of
      treatment. We aimed to determine whether the addition of DMT to dialysis fluid
      lowered plasma Hcy concentrations in a Continuous Ambulatory Peritoneal Dialysis
      sheep model using animals that were either in acute renal failure (n=3) or had
      normal renal function (n=1). Sub-acute exposure to DMT was toxic to all four
      animals, which died with total lung consolidation and collapse and Diffuse
      Alveolar Damage within 48 h of beginning treatment. Adverse side effects were
      observed after 4-8 doses. DMT was not detected in pre-dialysis plasma samples and
      the final concentration at death was 0.5-7.8 mmol/L, depending on the number of
      doses each animal was exposed to. Abnormalities were not observed in animals
      supplied standard dialysis fluid, or fluid with added glycine betaine. Toxicity
      associated with DMT treatment raises concerns for its use in further studies.
      However, sub-acute administration of DMT to sheep may provide a useful model of
      acute alveolar damage.

PMID- 17175150
TI  - Protection of PC12 cells from hydrogen peroxide-induced cytotoxicity by
      salvianolic acid B, a new compound isolated from Radix Salviae miltiorrhizae.
AB  - A number of studies indicate that reactive oxygen species (ROS) are involved in
      neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's
      disease (PD). The neuroprotective effects of salvianolic acid B (SalB) from Radix
      Salviae miltiorrhizae (RSM) against hydrogen peroxide (H2O2)-induced rat
      pheochromocytoma line PC12 injury were evaluated in the present study. Vitamin E,
      a potent antioxidant, was employed as a positive control agent. Following
      exposure of cells to H2O2 (150 microM), a marked decrease in cell survival and
      activities of superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GSH-Px), as well as increased levels of malondialdehyde (MDA)
      production and lactate dehydrogenase (LDH) release were observed. In parallel,
      H2O2 caused significant elevation in intracellular Ca2+ level and caspase-3
      activity, and induced apoptotic death as determined by flow cytometric assay.
      However, pretreatment of the cells with SalB (0.1-10 microM) prior to H2O2
      exposure blocked these H2O2-induced cellular events noticeably. Moreover, SalB
      exhibited significantly higher potency as compared to Vitamin E. The present
      findings indicated that SalB exerts neuroprotective effects against H2O2
      toxicity, which might be of importance and contribute to its clinical efficacy
      for the treatment of neurodegenerative diseases.

PMID- 17175151
TI  - The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed
      by alphaVbeta3 integrin in human breast cancer cells.
AB  - The influence of alphaVbeta3 integrin on MT1-MMP functionality was studied in
      human breast cancer cells of differing beta3 integrin status. Overexpression of
      beta3 integrin caused increased cell surface expression of alphaV integrin and
      increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549,
      MDA-MB-231 and MCF-7 cells. beta3 integrin expression also enhanced the migration
      of breast cancer cells on ECM substrates and enhanced collagen gel contraction.
      In vivo, alphaVbeta3 cooperated with MT1-MMP to increase the growth of MCF-7
      cells after orthotopic inoculation in immunocompromised mice, but had no
      influence on in vitro proliferation. Despite these stimulatory effects,
      overexpression of beta3 integrin suppressed the type I collagen (Col I) induced
      MMP-2 activation in all breast cancer cell lines analyzed. This was also evident
      in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated
      by MT1-MMP transfection, but attenuated with beta3 integrin expression. Although
      our studies confirm important biological effects of alphaVbeta3 integrin on
      enhancing cell adhesion and migration, ECM remodeling and tumor growth, beta3
      integrin caused reduced MMP-2 activation in response to Col I in vitro, which
      appears to be physiologically relevant, as it was also seen in tumor xenografts
      in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by
      alphaVbeta3 in response to Col I may be important in scenarios where cells which
      are activated for matrix degradation need to preserve some pericellular collagen,
      perhaps as a substrate for cell adhesion and migration, thus maintaining a
      balanced level of proteolysis required for efficient tumor growth.

PMID- 17175152
TI  - Understanding ERM proteins--the awesome power of genetics finally brought to
      bear.
AB  - In epithelial cells, the Ezrin, Radixin and Moesin (ERM) proteins are involved in
      many cellular functions, including regulation of actin cytoskeleton, control of
      cell shape, adhesion and motility, and modulation of signaling pathways. However,
      discerning the specific cellular roles of ERMs has been complicated by redundancy
      between these proteins. Recent genetic studies in model organisms have identified
      unique roles for ERM proteins. These include the regulation of morphogenesis and
      maintenance of integrity of epithelial cells, stabilization of intercellular
      junctions, and regulation of the Rho small GTPase. These studies also suggest
      that ERMs have roles in actomyosin contractility and vesicular trafficking in the
      apical domain of epithelial cells. Thus, genetic analysis has enhanced our
      understanding of these widely expressed membrane-associated proteins.

PMID- 17175154
TI  - Fly ash scrubbing in a novel dual flow scrubber.
AB  - Scrubbers are used as particulate emission control devices with the increase in
      stringency of old regulations or promulgation of new regulations. Scrubbing of
      fly ash in a novel dual flow scrubber, i.e., one water filled bubble section and
      one section with water-spray, is reported in this article. The presented system
      included a tapered section in order to achieve the bubble regime. On the other
      hand, a two-phase critical flow atomizer was used for the generation of spray
      regime with high degree of spray uniformity. Experiments were carried out for
      studying the behavior of the system in terms of various pertinent variables. The
      fly ash removal mechanism was explained in terms of various physical
      interactions. Electrostatic effect was found to have an insignificant influence
      on the collection efficiency of fly ash. The removal efficiency was found to
      decrease with the increase in inlet fly ash loading in the bubble section while
      it was increased in the spray section. A compromise must, therefore, be struck
      while operating the scrubber for achieving the desired performance. The effects
      of other operating variables studied on the removal efficiency remained similar
      in the regimes under investigation. The combined effect was, however, that the
      spray regime was dominating. Experimentation also revealed that the bubble
      section collected particles down to 20 microm size. Detailed experimentation
      revealed that almost 100% removal efficiency (zero penetration) of fly ash could
      be achieved in the dual flow scrubber at a QL/QG ratio of 3.0 m3/1000 ACM (actual
      cubic meter). Almost zero penetration of fly ash particles, clearly demonstrated
      that the dual flow scrubber with its staging operations met with the stricter
      emission regulations for particulate matter. Selection of any particulate control
      device is intrinsically related to the performance as a function of various
      pertinent variables of the system. Correlations were, therefore, put forward for
      the prediction of the performances of the bubble and the spray sections in terms
      of various pertinent variables of the system. The overall removal efficiency
      achievable in the dual flow scrubber was predicted with the help of these
      correlations. The predicted values were in excellent agreement with the
      experimental values (well within +/-5.0% deviation). Comparison of the
      performance of the present system with the existing systems indicated that the
      bubble and spray sections either alone or in combination (as in a dual flow
      scrubber), was energy and efficiency-wise much better than the existing systems.
      The novelty of the system is also described.

PMID- 17175153
TI  - What can myosin VI do in cells?
AB  - The recently solved structure of the myosin VI motor demonstrates that the unique
      insert at the end of the motor is responsible for the reversal of the normal
      myosin directionality. A second class-specific insert near the nucleotide-binding
      pocket contributes to myosin VI's unique kinetic tuning, allowing it to function
      either as an actin-based transporter or as an anchoring protein. Recent
      biochemical and biophysical studies have shown that the native molecule can form
      dimers upon clustering, and cell biological studies have demonstrated that it
      clearly does play both transport and anchoring roles in cells. These mechanistic
      insights allow us to speculate on how unusual aspects of myosin VI structure and
      function allow it to fill unique niches in cells.

PMID- 17175155
TI  - Development of amperometric horseradish peroxidase based biosensors for clozapine
      and for the screening of thiol compounds.
AB  - Two amperometric biosensors with immobilized horseradish peroxidase (HRP) were
      developed for the investigation of the clozapine drug oxidation and for thiols
      screening based on biosensor signal inhibition. The HRP was retained either in
      magnetized nanoporous silica microparticles (MMPs) or in a carbon paste (CP). The
      latter served for the carbon paste electrode while the MMPs were attracted in
      close proximity of a magnetized carbon electrode. The potential use of these
      configurations for drug oxidation and inhibition studies was illustrated by the
      enzymatic oxidation of clozapine (CLZ) in the presence of hydrogen peroxide. The
      biosensor signal corresponded to the electro-reduction of CLZ oxidation products
      namely a nitrenium ion (CLZox) generated by the enzyme HRP. Several thiols
      reactive towards CLZox were investigated and the biosensor signal inhibition
      (IC(50)) was comparatively determined. A protective effect of the nanoporous
      silica and carbon paste matrices towards HRP inactivation was inferred by
      comparing the biosensor inhibition results with those obtained with the free
      enzyme in solution.

PMID- 17175156
TI  - Development of a carbon nanotube paste electrode osmium polymer-mediated
      biosensor for determination of glucose in alcoholic beverages.
AB  - This paper describes a new amperometric biosensor for glucose monitoring. The
      biosensor is based on the activity of glucose dehydrogenase (GDH) and diaphorase
      (DI) co-immobilized with NAD(+) into a carbon nanotube paste (CNTP) electrode
      modified with an osmium functionalized polymer. This mediator was demonstrated to
      shuttle the electron transfer between the immobilized diaphorase and the CNTP
      electrode, thus, showing a good electrocatalytic activity towards NADH oxidation
      at potentials around +0.2V versus Ag|AgCl, where interfering reactions are less
      prone to occur. The biosensor exhibits a detection limit of 10 micromol L(-1),
      linearity up to 8 x 10(-4) mol L(-1), a sensitivity of 13.4 microA cm(-2)mmol(
      1)L(-1), a good reproducibility (R.S.D. 2.1%, n=6) and a stability of about 1
      week when stored dry at 4 degrees C. Finally, the proposed biosensor was applied
      for the determination of glucose in different samples of sweet wine and validated
      with a commercial spectrophotometric enzymatic kit.

PMID- 17175157
TI  - Real time monitoring of the effects of Heparan Sulfate Proteoglycan (HSPG) and
      surface charge on the cell adhesion process using thickness shear mode (TSM)
      sensor.
AB  - The effects of Heparan Sulfate Proteoglycan (HSPG) and surface charge on the
      cellular interactions of the cell membrane with different substrates to determine
      the kinetics of cell adhesion was studied using thickness shear mode (TSM)
      sensor. The TSM sensor was operated at its first, third, fifth and seventh
      harmonics. Since the penetration depth of the shear wave decreases with increases
      in frequency, the multi-resonance operation of the TSM sensor was used to monitor
      the changes in the kinetics of the cell-substrate interaction at different
      distances from the sensor surface. During the sedimentation and the initial
      attachment of the cells on the sensor surface, the changes in the sensor resonant
      frequency and the magnitude response were monitored. First, HSPGs were partially
      digested with the enzyme Heparinase III to evaluate the effect of HSPG on the
      cell adhesion process. The results indicated that HSPG did not have any effect on
      the kinetics of the initial attachment, but it did reduce the strength of steady
      state cell adhesion. Next, we investigated the effect of the electrostatic
      interactions of the cell membrane with the substrate on the cell adhesion. In
      this case, the sensor surface was coated with positively charged Poly-D-Lysine
      (PDL). It was observed that electrostatic interaction of the negatively charged
      cell membrane with the PDL surface promoted the initial cell adhesion but did not
      support long-term cell adhesion. The multi-resonant TSM technique was shown to be
      a very promising method for monitoring specific interfacial effects involving in
      cell adhesion process in real-time.

PMID- 17175158
TI  - Demonstration of anaerobic stabilization of black water in accumulation systems
      under tropical conditions.
AB  - The anaerobic digestion of "human waste" was studied at Mlalakuwa residential
      settlement in Dar-es-Salaam, Tanzania at ambient tropical temperatures (24-31
      degrees C). This settlement experiences a high water table with flooding during
      the rainy season, resulting in a very costly emptying of the latrines once per
      month. To improve the situation, two plastic tanks (while one is in use, the
      other one is on stand-by) of 3000 l capacity each, named as Improved Pit-Latrines
      Without Urine Separation (IMPLWUS), were used as latrine pits. They received
      faeces+urine+wash water; basically, an accumulation system. Septic tank seed
      sludge was used. The dissolved chemical oxygen demand (COD(dis)) remaining when
      the reactor was closed after 380 days was about 8 g COD/l, volatile fatty acids
      were 100 mg COD/l and total ammonium nitrogen was about 2.8 g N/l, implying the
      possibility of methanogenesis inhibition. Stability results indicated a need for
      more degradation time after reactor closure. Estimated biogas production from
      wastewater generated by 10 people was 544 g COD-CH(4)/day, not enough for cooking
      purposes.

PMID- 17175159
TI  - A new approach of pellet formation of a filamentous fungus -Rhizopus oryzae.
AB  - The effects of inoculum and medium composition (i.e. potato dextrose broth as
      carbon source, soybean peptone, calcium carbonate, and metal ions) on pellet
      formation of Rhizopus oryzae ATCC 20344 have been studied. Metal ions were found
      to have a significant negative effect on pellet formation while soybean peptone
      had a positive effect. In addition, potato dextrose broth and calcium carbonate
      were beneficial to R. oryzae for growing small, smooth pellets during the
      culture. The study also demonstrated that an inoculum size of less than
      1.5x10(9)spores/L had no significant influence on pellet formation although it
      had large impacts on pellet growth. Thus, a new approach to form pellets has been
      developed using only potato dextrose broth, soybean peptone, and calcium
      carbonate allowing for pellet size to be controlled by adjusting inoculum size
      and the concentrations of potato dextrose broth, soybean peptone, and calcium
      carbonate in the medium.

PMID- 17175160
TI  - 1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists. Structure-activity
      relationships of 6-substituted and 5,6-disubstituted benzoic acid derivatives.
AB  - Herein we describe the SAR of 1,5-biaryl pyrrole derivatives, with substituents
      in the 6-position of the benzoic acid moiety, as EP(1) receptor antagonists.
      Substitution at this position was well tolerated and led to the identification of
      several analogues with high affinity for the EP(1) receptor that displayed good
      efficacy in the established FCA model of inflammatory pain. Furthermore, several
      analogues were prepared which combined substitution at the 5- and 6-positions as
      well as derivatives with an aromatic ring fused to the 5- and 6-positions.

PMID- 17175161
TI  - Meta-analysis of clinical outcomes following surgical mitral valve repair or
      replacement.
AB  - Although the use of mitral valve surgery has been successful at alleviating
      mitral valve disease, published studies on either replacement or repair have
      yielded mixed clinical outcomes regarding differences between repair and
      replacement. Meta-analysis of various outcomes from 29 published studies was
      conducted. Studies were separated into four groups by etiology of disease:
      ischemic; degenerative/myxomatous; rheumatic and mixed. The summary odds ratio
      for early mortality, comparing replacement to repair, was 2.24 (1.78-2.80), while
      the summary total survival hazard ratio was 1.58 (1.41-1.78), replacement
      compared to repair, indicating worse outcomes among those undergoing mitral valve
      replacement. The risk of thromboembolism was lower in the repair group (summary
      hazard ratio=1.86, replacement vs. repair), while there was no statistical
      difference in time to re-operation between the two treatment groups (hazard
      ratio=0.88 [95% confidence interval: 0.48, 1.62]). Analysis stratified by
      etiologic classification was able to detect strong evidence of differences in 30
      day and total survival outcomes favoring repair for three disease groups
      (rheumatic, mixed and degenerative). Surgery for ischemic mitral valve had lower
      30-day mortality for repair than replacement, but no statistically significant
      difference in the overall survival was detected. The reported information in the
      published studies used in the current work lacks sufficient detail to allow
      summary determination of outcomes by mitral valve repair techniques and by type
      of mitral valve replacement.

PMID- 17175162
TI  - Unveiling gender differences in demand ischemia: a study in a rat model of
      genetic hypertension.
AB  - OBJECTIVE: Female gender is associated with reduced tolerance against acute
      ischemic events and a higher degree of left ventricular hypertrophy under chronic
      pressure overload. We tested whether female and male rats with left ventricular
      hypertrophy present the same susceptibility to demand ischemia. METHODS: Hearts
      from hypertrophied female and male salt-resistant and salt-sensitive Dahl rats
      (n=8 per group) underwent 30min of demand ischemia induced by rapid pacing (7Hz)
      and an 85% reduction of basal coronary blood flow, followed by 30min of
      reperfusion on an isovolumic red cell perfused Langendorff model. RESULTS: In
      female hearts, high-salt diet induced a pronounced hypertrophy of the septum
      (2.38+/-0.09 vs 2.17+/-0.08mm; p<0.01), whereas male hearts showed the greatest
      increase in the anterior/posterior wall of the left ventricle (LV) (3.19+/-0.22
      vs 2.01+/-0.16mm; p<0.05) compared with salt-resistant controls. At baseline, LV
      developed pressure/g LV was significantly higher in female than male hearts
      (200+/-13 and 196+/-14 vs 161+/-10 and 152+/-15mmHgg(-1); p<0.01), independent of
      hypertrophy, indicating greater contractility in females. During ischemia, LV
      developed pressure decreased in all groups; at the end of reperfusion,
      hypertrophied female and male hearts showed higher developed pressures
      independent of gender (148+/-3 and 130+/-8 vs 100+/-7 and 85+/-6mmHg; p<0.01). In
      contrast, diastolic pressure was more pronounced in female than in male
      hypertrophied hearts during ischemia and reperfusion (24+/-3 vs 12+/-2mmHg;
      p<0.01). CONCLUSIONS: In the pressure overload model of the Dahl salt-sensitive
      rat, female gender is associated with a more pronounced concentric hypertrophy,
      whereas male hearts develop a more eccentric type of remodeling. Although present
      at baseline, after ischemia/reperfusion systolic function is gender-independent
      but more determined by hypertrophy. In contrast, diastolic function is gender
      dependent and aggravated by hypertrophy, leading to pronounced diastolic
      dysfunction. We can conclude that in the malignant setting of demand
      ischemia/reperfusion gender differences in hypertrophied hearts are unmasked:
      female hypertrophied hearts are more susceptible to ischemia/reperfusion than
      males. To determine whether in female hypertensive patients with acute coronary
      syndromes, diastolic dysfunction could contribute to the worse clinical course,
      further experimental and clinical studies are needed.

PMID- 17175163
TI  - The approach of fused fissures with fissureless technique decreases the incidence
      of persistent air leak after lobectomy.
AB  - OBJECTIVE: To evaluate two different approaches used to perform fused fissures in
      lobectomies in terms of persistent air leak (PAL) and their impact on length of
      hospital stay. METHODS: One hundred and nineteen patients underwent lobectomy or
      bilobectomy in our unit. We focused on patients with fused fissures (63
      patients), all of whom were selected intraoperatively based on predefined
      criteria. These patients with incomplete fissures were randomly assigned to two
      groups: Group A patients who underwent a 'traditional technique' to approach
      fused fissures and Group B patients who underwent a 'fissureless technique'. The
      latter technique avoids dissecting the lung parenchyma over the pulmonary artery,
      reducing the chances of air leak. Patients in both groups had shown no
      significant difference in preoperative variables (p>0.05). RESULTS: The incidence
      of PAL was significantly higher among patients with incomplete or fused fissures
      (0 case vs 8 cases (Groups A and B), p<0.005). Furthermore, the incidence of PAL
      was significantly higher in the Group A (traditional technique) (7 vs 1) (p<0.05,
      OR=3.1, CI 0.22-0.51). The probability for air leak cessation was significantly
      higher in patients of Group B (fissureless technique) (log rank p<0.0001). The
      length of hospital stay was higher in Group A (5.76+/-3.1) compared with Group B
      (4.9+/-1.7) (p<0.05). No other variables were identified as risk factors for PAL
      in this series. CONCLUSIONS: The fissureless technique appears to be a superior
      approach for fused fissures in terms of both preventing persistent air leak and
      reducing the length of hospitalisation. This technique can be performed safely at
      no additional cost and without adverse consequences.

PMID- 17175164
TI  - Pharmacokinetics of tramadol enantiomers and their respective phase I metabolites
      in relation to CYP2D6 phenotype.
AB  - OBJECTIVE: Our objective was to evaluate the effect of CYP2D6 phenotype in the
      enantioselective metabolism of tramadol in Spanish healthy human volunteers.
      METHODS: A single oral 100mg dose of racemic tramadol was administered to five
      subjects who were poor metabolizers (PMs) and 19 subjects who were extensive
      metabolizers (EMs), whose phenotypes were determined by the use of the racemic
      tramadol metabolic rate. The pharmacokinetic parameters were estimated from
      plasma concentrations of the enantiomers of tramadol and their main phase I
      metabolites, O-desmethyltramadol (M1) and N-desmethyltramadol (M2). Epinephrine
      plasma concentrations were also determinated. RESULTS: The plasma concentrations
      of both tramadol enantiomers were consistently higher in PMs than in EMs of
      CYP2D6, with 1.98- and 1.74-fold differences in the mean area under the plasma
      concentration-time curves (AUC), respectively. The values for oral clearance of
      (+)- and (--)-tramadol were 1.91- and 1.71-fold greater in PMs, which were
      related to differences in both O-desmethylation and N-desmethylation in the two
      CYP2D6 metabolizer phenotypes. The mean AUC values of (+)-M1 and (--)-M1 were
      4.33- and 0.89-fold greater in EMs, and it was related to similar differences in
      the formation rate constant. On the other hand, the differences were 7.40- and
      8.69-fold greater in PMs for M2 enantiomers due to the involvement of CYP2D6 in
      their subsequent biotransformation. The time course of epinephrine systemic
      concentrations was completely different between both groups of metabolizers. In
      EMs plasma concentrations of epinephrine increased after tramadol administration
      whereas in PMs no effect was observed. CONCLUSIONS: The polymorphic CYP2D6
      appears to be a major enzyme involved in the metabolism of tramadol enantiomers.
      The N-desmethylation pathway was indirectly affected by CYP2D6 phenotypic
      differences. Epinephrine showed a good correlation with the pharmacokinetics of
      the opioid component of tramadol, (+)-M1 and was found to be useful for its
      pharmacodynamic profiling.

PMID- 17175165
TI  - Phosphorylation of the NF2 tumor suppressor in Schwann cells is mediated by Cdc42
      Pak and requires paxillin binding.
AB  - Mutations in the Neurofibromatosis type 2 tumor suppressor gene that encodes
      Schwannomin causes formation of benign schwannomas. Schwannoma cells lose their
      characteristic bipolar shape and become rounded with excessive ruffling
      membranes. Schwannomin is phosphorylated at serine 518 (S518) by p21 activated
      kinase (Pak). Unphosphorylated schwannomin is associated with growth inhibition
      but little is known about the function of the phosphorylated form, or the
      molecular events leading to its phosphorylation. Here, we report in SCs that
      schwannomin S518 phosphorylation requires binding to paxillin and targeting to
      the plasma membrane. Phospho-S518-schwannomin is enriched in the peripheral-most
      aspects of membrane specializations where paxillin, activated Pak, Cdc42 but not
      Rac are highly expressed. Schwannomin and Pak phosphorylation levels are not
      reduced in response to lowering Rac-GTP levels with NSC23766. Expression of
      schwannomin S518A/D-GFP variants each distinctively altered Schwann cell shape
      and polarity. These results are consistent with tight spatial regulation of S518
      phosphorylation at the plasma membrane in a paxillin and Cdc42-Pak dependent
      manner that leads to local reorganization of the SC cytoskeleton.

PMID- 17175167
TI  - Identification, cloning, expression, and characterization of a highly
      thermostable single-stranded-DNA-binding protein (SSB) from Deinococcus murrayi.
AB  - We report identification and characterization of SSB-like protein from
      Deinococcus murrayi (DmuSSB). PCR-derived DNA fragment containing the complete
      structural gene for DmuSSB was cloned and expressed in Escherichia coli. The gene
      consisted of an open reading frame of 826 nucleotides encoding a protein of 276
      amino acid residues with a calculated molecular weight of 30.14 kDa. DmuSSB
      includes two OB folds per monomer and functions as a homodimer. In fluorescence
      titrations with poly(dT) DmuSSB bound 27-32 nt depending on the salt
      concentration, and fluorescence was quenched by about 62%. In a complementation
      assay in E. coli, DmuSSB took over the in vivo function of EcoSSB. DmuSSB
      maintained 100% activity after 120 min incubation at 80 degrees C, with half
      lives of 50 min at 95 degrees C, 40 min at 100 degrees C and 35 min at 105
      degrees C. DmuSSB is the most thermostable SSB-like protein identified to date,
      offering an attractive alternative for TaqSSB and TthSSB in their applications
      for molecular biology methods and for analytical purposes.

PMID- 17175166
TI  - Expression and purification of phosphorylated and non-phosphorylated human MEK1.
AB  - Kinases exist in either a high or low activity form depending on the
      phosphorylation state of the activating lip. These two different forms of the
      same kinase may adopt different conformations that affect not only activity but
      also inhibitor binding and the ability to crystallize the protein. Therefore,
      isolation of homogenous preparations of the phosphorylated and non-phosphorylated
      versions of a kinase is critical for accurate biophysical measurements of
      activity, stability and ligand binding as well as for protein crystallization.
      The aim of the present study is the expression, purification and characterization
      of recombinant human MEK1 protein in both the activated and low-activity states.
      A baculovirus co-expression system was developed for obtaining high levels of
      activated, phosphorylated human MEK1 kinase. High-Five cells were co-infected
      with human MEK1 virus and Raf-BXB, an untagged constitutively active version of
      Raf which is the activating kinase for MEK1. Unphosphorylated MEK1 was generated
      by treating MEK1 isolated from High-Five baculovirus expression with lambda
      phosphatase. The proteins were characterized by SDS-PAGE, LC-MS, Western
      blotting, enzymatic activity, and circular dichroism. Previous reports of MEK1
      expression and purification yielded lower levels of protein and purity. The yield
      using High-Five cells was 5mg/L for phosphorylated MEK1 and 10mg/L for
      unphosphorylated MEK1. For phosphorylated MEK1, the specific activity was
      3530U/mg, the IC(50) values for the non-specific kinase inhibitors K252a and
      K252b were 8 and 47nM, respectively, and the IC(50) for the MEK1 non-ATP
      competitive inhibitor, PD0325901, was 43nM.

PMID- 17175168
TI  - Contributions of molecular epidemiology to the understanding of infectious
      disease transmission, pathogenesis, and evolution.
AB  - PURPOSE: Describe the contributions of molecular genetics to our understanding of
      the molecular epidemiology of infectious diseases caused by bacteria. METHODS:
      Synthesize the literature, highlighting work on Escherichia coli and Group B
      streptococcus. RESULTS: 1) Commensal bacteria are genetically and phenotypically
      diverse. 2) Disease-causing strains of commensal bacteria often have special
      characteristics than allow them to be distinguished from common inhabitants. 3)
      Colonization by commensal bacteria is dynamic. 4) Commensal bacteria are
      transmitted between individuals. CONCLUSIONS: Applications of epidemiologic
      principles to bacterial populations gives insight into the natural history of
      colonization and transmission in the human host.

PMID- 17175170
TI  - Defining and solving the essential protein-protein interactions in HIV infection.
AB  - The structure determination of macromolecular complexes is entering a new era.
      The methods of optical microscopy, electron microscopy, X-ray crystallography,
      and nuclear magnetic resonance increasingly are being combined in hybrid method
      approaches to achieve an integrated view of macromolecular complexes that span
      from cellular context to atomic detail. A particularly important application of
      these hybrid method approaches is the structural analysis of the Human
      Immunodeficiency Virus (HIV) proteins with their cellular binding partners. High
      resolution structure determination of essential HIV - host cell protein complexes
      and correlative analysis of these complexes in the live cell can serve as
      critical guides in the design of a broad, new class of therapeutics that function
      by disrupting such complexes. Here, with the hope of stimulating some discussion,
      we will briefly review some of the literature in the context of what could be
      done to further apply structural methods to HIV research. We have chosen to focus
      our attention on certain aspects of the HIV replication cycle where we think that
      structural information would contribute substantially to the development of new
      therapeutic and vaccine targets for HIV.

PMID- 17175169
TI  - Hierarchical assembly of the siliceous skeletal lattice of the hexactinellid
      sponge Euplectella aspergillum.
AB  - Despite its inherent mechanical fragility, silica is widely used as a skeletal
      material in a great diversity of organisms ranging from diatoms and radiolaria to
      sponges and higher plants. In addition to their micro- and nanoscale structural
      regularity, many of these hard tissues form complex hierarchically ordered
      composites. One such example is found in the siliceous skeletal system of the
      Western Pacific hexactinellid sponge, Euplectella aspergillum. In this species,
      the skeleton comprises an elaborate cylindrical lattice-like structure with at
      least six hierarchical levels spanning the length scale from nanometers to
      centimeters. The basic building blocks are laminated skeletal elements (spicules)
      that consist of a central proteinaceous axial filament surrounded by alternating
      concentric domains of consolidated silica nanoparticles and organic interlayers.
      Two intersecting grids of non-planar cruciform spicules define a locally
      quadrate, globally cylindrical skeletal lattice that provides the framework onto
      which other skeletal constituents are deposited. The grids are supported by
      bundles of spicules that form vertical, horizontal and diagonally ordered struts.
      The overall cylindrical lattice is capped at its upper end by a terminal sieve
      plate and rooted into the sea floor at its base by a flexible cluster of barbed
      fibrillar anchor spicules. External diagonally oriented spiral ridges that extend
      perpendicular to the surface further strengthen the lattice. A secondarily
      deposited laminated silica matrix that cements the structure together
      additionally reinforces the resulting skeletal mass. The mechanical consequences
      of each of these various levels of structural complexity are discussed.

PMID- 17175171
TI  - Repeated sampling of individual bivalve mollusks I: intraindividual variability
      and consequences for haemolymph constituents of the Manila clam, Ruditapes
      philippinarum.
AB  - Components of the haemolymph are understood to constitute the internal defense
      system of bivalve mollusks and their levels are often considered to be indicators
      of "health"; however, relatively little proof exists of the role that these
      elements play in the success or failure of defense against a pathogen. A change
      associated with infection may be the consequence of disease rather than a measure
      of the capacity to respond effectively to a pathogen. One way to assess whether
      haemocyte or serum-component concentrations are related to resistance to
      microbial infection is to sample individuals over time, both before and after
      they are experimentally or naturally infected. But sampling itself may alter the
      parameter being assessed. In addition, interindividual variation is large and the
      degree of intraindividual variation over time is largely unknown. To evaluate
      intra- vs interindividual variability measured over time and to assess the
      effects of repeated sampling, we subjected Manila clams, Ruditapes philippinarum,
      to multiple haemolymph samplings during both field and laboratory experiments,
      and measured four parameters: haemocyte density, protein concentration, and the
      activities of leucine amino peptidase and DOPA-oxidase. A repeated-measures ANOVA
      indicated that individuals with high or low levels at one sampling, tended to
      have high or low levels, respectively, at the other sampling times. Furthermore,
      the index of individuality, which is the ratio of intra- to interindividual
      variability, for these four parameters was comparable to that for human serum
      components. Repeated sampling had no measured effect on field-deployed clams,
      which were sampled at intervals of 1-3 months, but significantly depressed values
      in laboratory-held clams sampled at 1-month intervals. Results demonstrated
      relative intraindividual constancy in the measured variables and suggested that
      minimizing sample frequency and volume, and maintaining animals in a
      comparatively natural environment should all facilitate repeated sampling with
      minimum injury to experimental mollusks.

PMID- 17175173
TI  - Empathy for positive and negative emotions in the gustatory cortex.
AB  - Anterior insula and adjacent frontal operculum (hereafter referred to as IFO) are
      active during exposure to tastants/odorants (particularly disgusting ones), and
      during the viewing of disgusted facial expressions. Together with lesion data,
      the IFO has thus been proposed to be crucial in processing disgust-related
      stimuli. Here, we examined IFO involvement in the processing of other people's
      gustatory emotions more generally by exposing participants to food-related
      disgusted, pleased and neutral facial expressions during functional magnetic
      resonance imaging (fMRI). We then exposed participants to pleasant, unpleasant
      and neutral tastants for the purpose of mapping their gustatory IFO. Finally, we
      associated participants' self reported empathy (measured using the Interpersonal
      Reactivity Index, IRI) with their IFO activation during the witnessing of others'
      gustatory emotions. We show that participants' empathy scores were predictive of
      their gustatory IFO activation while witnessing both the pleased and disgusted
      facial expression of others. While the IFO has been implicated in the processing
      of negative emotions of others and empathy for negative experiences like pain,
      our finding extends this concept to empathy for intense positive feelings, and
      provides empirical support for the view that the IFO contributes to empathy by
      mapping the bodily feelings of others onto the internal bodily states of the
      observer, in agreement with the putative interoceptive function of the IFO.

PMID- 17175174
TI  - Magnetoencephalographic analysis of cortical oscillatory activity in patients
      with brain tumors: Synthetic aperture magnetometry (SAM) functional imaging of
      delta band activity.
AB  - Abnormal focal slow wave activity on electroencephalography and
      magnetoencephalography (MEG) is often seen in patients with various brain
      pathologies and MEG is capable of localizing cortical oscillatory activity with
      enhanced accuracy. In addition, MEG with synthetic aperture magnetometry (SAM)
      can depict changes in cortical oscillatory activity tomographically. Using SAM,
      we recorded cortical rhythms in patients with a brain tumor and evaluated the
      tomographic appearance of focal slow wave activity in relation to clinical signs
      and symptoms. Spontaneous MEG recordings were obtained in 15 patients with brain
      tumors. Statistically-determined power distributions in the delta-, theta-, and
      alpha-frequency bands were displayed tomographically and overlaid on individual
      magnetic resonance images. The location, strength and volume of enhanced activity
      were analyzed. Delta and theta band activities were significantly more intense in
      the cortex adjacent to tumors and in the surrounding edematous cortical areas
      than in other portions of the cortex. In 13 of the 15 patients, spatial
      distribution of enhanced focal delta activity coincided with the area responsible
      for the presenting signs and symptoms. Volumetric analysis revealed that
      emergence of tumor-related focal delta band activity in the cortex adjacent to a
      tumor, or with peritumoral edema, was greater for intra-axial tumors involving
      subcortical fibers than for extra-axial tumors. Patients with an increased volume
      of enhanced delta activity exhibited poor recovery of function in the early
      postoperative period. It is concluded that SAM imaging of focal delta activity
      can reveal functional alterations in cortical activity in patients with brain
      tumors and is useful for assessing cortical states associated with the existing
      pathology.

PMID- 17175172
TI  - Protection of shrimp (Penaeus chinensis) against white spot syndrome virus (WSSV)
      challenge by double-stranded RNA.
AB  - To determine whether Penaeus chinensis can be protected against white spot
      syndrome virus (WSSV) infection by intramuscular injection with long double
      stranded RNAs (dsRNAs) as in other shrimp species and whether the protection
      degree by WSSV-specific dsRNAs is correlated with the roles of viral genes, P.
      chinensis juveniles were intramuscularly injected with long dsRNAs corresponding
      to VP28, VP281, protein kinase genes of WSSV, and an unrelated long dsRNA
      corresponding to a green fluorescence protein (GFP) gene. All shrimp injected
      with long dsRNAs including GFP dsRNA showed higher survival rates against WSSV
      infection than shrimp injected with PBS alone. Furthermore, shrimp injected with
      dsRNAs corresponding to VP28 and protein kinase showed higher survival rates than
      those injected with dsRNAs corresponding to VP281 and GFP. These results indicate
      that the introduction of long dsRNAs corresponding to viral proteins, which are
      essential for WSSV infection, is quite effective in blocking WSSV infection in P.
      chinensis, and suggest that dsRNA-mediated protection is a common feature across
      shrimp species.

PMID- 17175175
TI  - Changes in neuronal connectivity after stroke in rats as studied by serial
      manganese-enhanced MRI.
AB  - Loss of function and subsequent spontaneous recovery after stroke have been
      associated with physiological and anatomical alterations in neuronal networks in
      the brain. However, the spatiotemporal pattern of such changes has been
      incompletely characterized. Manganese-enhanced MRI (MEMRI) provides a unique tool
      for in vivo investigation of neuronal connectivity. In this study, we measured
      manganese-induced changes in longitudinal relaxation rate, R(1), to assess the
      spatiotemporal pattern of manganese distribution after focal injection into the
      intact sensorimotor cortex in control rats (n=10), and in rats at 2 weeks after
      90-min unilateral occlusion of the middle cerebral artery (n=10). MEMRI data were
      compared with results from conventional tract tracing with wheat-germ agglutinin
      horseradish peroxidase (WGA-HRP). Distinct areas of the sensorimotor pathway were
      clearly visualized with MEMRI. At 2 weeks after stroke, manganese-induced changes
      in R(1) were significantly delayed and diminished in the ipsilateral caudate
      putamen, thalamus and substantia nigra. Loss of connectivity between areas of the
      sensorimotor network was also identified from reduced WGA-HRP staining in these
      areas on post-mortem brain sections. This study demonstrates that MEMRI enables
      in vivo assessment of spatiotemporal alterations in neuronal connectivity after
      stroke, which may lead to improved insights in mechanisms underlying functional
      loss and recovery after stroke.

PMID- 17175176
TI  - Dissociated lateralization of transient and sustained blood oxygen level
      dependent signal components in human primary auditory cortex.
AB  - Among other auditory operations, the analysis of different sound levels received
      at both ears is fundamental for the localization of a sound source. These so
      called interaural level differences, in animals, are coded by excitatory
      inhibitory neurons yielding asymmetric hemispheric activity patterns with
      acoustic stimuli having maximal interaural level differences. In human auditory
      cortex, the temporal blood oxygen level-dependent (BOLD) response to auditory
      inputs, as measured by functional magnetic resonance imaging (fMRI), consists of
      at least two independent components: an initial transient and a subsequent
      sustained signal, which, on a different time scale, are consistent with
      electrophysiological human and animal response patterns. However, their specific
      functional role remains unclear. Animal studies suggest these temporal components
      being based on different neural networks and having specific roles in
      representing the external acoustic environment. Here we hypothesized that the
      transient and sustained response constituents are differentially involved in
      coding interaural level differences and therefore play different roles in spatial
      information processing. Healthy subjects underwent monaural and binaural acoustic
      stimulation and BOLD responses were measured using high signal-to-noise-ratio
      fMRI. In the anatomically segmented Heschl's gyrus the transient response was
      bilaterally balanced, independent of the side of stimulation, while in opposite
      the sustained response was contralateralized. This dissociation suggests a
      differential role at these two independent temporal response components, with an
      initial bilateral transient signal subserving rapid sound detection and a
      subsequent lateralized sustained signal subserving detailed sound
      characterization.

PMID- 17175178
TI  - Spatial intralobar correlation of spike and slow wave activity localisations in
      focal epilepsies: a MEG analysis.
AB  - 12 patients with focal epilepsy were examined by magnetoencephalography (MEG).
      Source localisations of interictal epileptiform activity (spikes) yielded clear
      results. Slow wave dipole density in the frequency range from 2 to 6 Hz, using
      time selections from an automatic principal component analysis (PCA), was
      calculated. Results of spike and slow wave dipole density localisations were
      superimposed on MR-images of each patient. Slow wave dipole densities were
      increased close to spike localisations. Distances between spike center of mass
      and slow wave maxima were calculated, average mean distance was 2.0 cm.
      Independant of the localisation in either TLE or ETLE a concordance of slow wave
      and spike localisations were found. Slow wave localisations were found in
      patients with lesions in MRI and patients with no abnormalities on the MRI. In
      comparison to healthy subjects, slow wave dipole density in patients with
      epilepsy was clearly increased. The localisation of slow wave dipole density
      yielded additional important information and may contribute to defining the
      irritative zone.

PMID- 17175179
TI  - Temporal dynamics of basal ganglia response and connectivity during verbal
      working memory.
AB  - Research on the neural basis of working memory (WM) has generally focused on
      neocortical regions; comparatively little is known about the role of subcortical
      structures. There is growing evidence that the basal ganglia are involved in WM,
      but their contribution to different component processes of WM is poorly
      understood. We examined the temporal dynamics of basal ganglia response and
      connectivity during the encoding, maintenance and response phases of a Sternberg
      WM task. During the encoding and maintenance phases, WM-load-dependent activation
      was observed in the left anterior caudate, anterior putamen and globus pallidus;
      activation in the right anterior caudate was observed only during the maintenance
      phase. During the response phase, the basal ganglia were equally active in both
      the high-load and low-load WM conditions. Caudate and putamen activations were
      primarily localized to the (rostral) associative parts of the basal ganglia,
      consistent with the putative role of these regions in cognitive processing.
      Effective connectivity analyses revealed increased WM-load-dependent interaction
      of the left anterior caudate with the left posterior parietal cortex during all
      three phases of the task; with the visual association cortex, including the
      fusiform gyrus and inferior temporal gyrus, only during the encoding phase; with
      the ventrolateral prefrontal cortex during the encoding and maintenance phases;
      with the pre-supplementary motor area during the maintenance and response phases;
      and with the dorsolateral prefrontal and anterior cingulate cortices only during
      the response phase. Taken together with known neuroanatomy of the basal ganglia,
      these results suggest that the anterior caudate helps to link signals in distinct
      functional networks during different phases of the WM task. Our study offers new
      insight into the integrative and adaptive role of the basal ganglia in higher
      cognitive function.

PMID- 17175177
TI  - [123I]epidepride binding to cerebellar dopamine D2/D3 receptors is displaceable:
      implications for the use of cerebellum as a reference region.
AB  - The low density of cerebellar dopamine D(2)/D(3) receptors provides the basis for
      using the cerebellum as a representation of free- and non-specifically bound
      radioligand in positron emission tomography (PET) and single photon emission
      computed tomography (SPECT) studies. With the development of ultra high-affinity
      dopamine D(2)/D(3) ligands like [(123)I]epidepride, [(18)F]fallypride, and
      [(11)C]FLB-457, quantification of extrastriatal low density receptor populations
      including the cerebellum is possible with important implications for calculation
      of binding parameters. [(123)I]epidepride-SPECT was performed in 23 patients with
      schizophrenia before and after 3 months of antipsychotic treatment with either
      risperidone (n=14) or zuclopenthixol (n=9). In the unblocked situation and
      partially blocked situation, the average distribution volumes were 5.2+/-1.3
      mL/mL and 4.0+/-0.8 mL/mL, respectively. The paired distribution volumes were
      reduced by 22+/-15% (mean+/-SD) after antipsychotic treatment (p<0.0001, paired
      Student's t-test). From the paired distribution volumes in cerebellum and
      extrastriatal regions, the average distribution volume representing free and non
      specifically bound [(123)I]epidepride was calculated to be 3.3+/-0.8 mL/mL. Both
      the % [(123)I]epidepride fraction of plasma radioactivity (p>0.76) and the plasma
      [(123)I]epidepride concentration (p>0.45) were unchanged after antipsychotic
      treatment (paired Student's t-test). These results strongly suggest the presence
      of "non-negligible" specific [(123)I]epidepride binding to dopamine D(2)/D(3)
      receptors in the cerebellum. Using the cerebellum as a representation of free and
      non-specifically bound radioligand and neglecting the specifically bound
      component may lead to results that erroneously imply that antipsychotic drugs
      bind to extrastriatal dopamine D(2)/D(3) receptors with a higher affinity than to
      striatal dopamine D(2)/D(3) receptors.

PMID- 17175180
TI  - Expression and function of TbetaRII-B, a variant of the type II TGF-beta
      receptor, in human chondrocytes.
AB  - OBJECTIVE: Transforming growth factor-beta (TGF-beta) has profound effects on
      chondrocyte proliferation and matrix production, and dysregulation of TGF-beta
      action has been implicated in osteoarthritis. The mechanisms by which the diverse
      actions of TGF-beta are regulated in chondrocytes are unclear. Although it is
      well documented that TGF-beta signaling is transduced by types I and II
      receptors, other TGF-beta receptors may play critical roles by regulating
      signaling receptor activity. Our objective was to examine the expression of
      TbetaRII-B, a splice variant of the type II TGF-beta receptor, and to analyze its
      role in regulating TGF-beta signaling in human chondrocytes. METHODS: TbetaRII-B
      expression was examined in human cartilage tissue specimens, human chondrocyte
      cell lines C28/I2 and tsT/AC62, and human primary chondrocytes by Western blot
      and reverse-transcriptase-polymerase chain reaction. Ligand binding and
      heteromerization of TbetaRII-B with other TGF-beta receptors on the cell surface
      were analyzed by affinity labeling, immunoprecipitation, and two-dimensional SDS
      PAGE. Regulation of TGF-beta responses by TbetaRII-B was determined by examining
      Smad2 phosphorylation, Smad3-specific signaling, transcriptional activity, and
      type II collagen levels. RESULTS: TbetaRII-B is expressed in normal and
      osteoarthritic human cartilage. Furthermore, it is a dynamic component of the TGF
      beta receptor system in human chondrocytes, forming heteromeric complexes with
      the types I and II TGF-beta receptors, betaglycan and endoglin. Importantly,
      overexpression of TbetaRII-B leads to enhanced TGF-beta signaling and responses
      in chondrocytes. CONCLUSIONS: These results suggest that TbetaRII-B may play a
      key role in the regulation of TGF-beta action in human chondrocytes.

PMID- 17175181
TI  - Apoptosis in raloxifene-treated postmenopausal women.
AB  - As raloxifene is a mixed estrogen receptor agonist and antagonist, it exerts
      different effects on apoptosis in different tissues. In this study, we aimed to
      evaluate apoptosis in the peripheral lymphocytes of postmenopausal women treated
      with raloxifene and compare it with untreated control subjects. In this way, we
      expected to deduce some results about the effect of raloxifene on the immune
      system and to serve as a guide for future studies on this newly proposed effect
      of a well-known agent. Twenty osteoporotic postmenopausal women treated with
      raloxifene for 12 months were included in this study. Another 20 osteoporotic
      postmenopausal women matched for age and postmenopausal years, but without any
      medication, were chosen as the control group. Apoptosis was evaluated using a
      morphological and DNA fragmentation assay, in the peripheral lymphocytes of these
      women. Our results revealed a decrease in the apoptosis percentages of the
      patients treated with raloxifene (14.6%) with respect to the control subjects
      (15.8%), but the difference was not statistically significant (p=0.467). This
      study indicated that raloxifene treatment had no apoptotic effect on peripheral
      human lymphocytes compared to controls.

PMID- 17175182
TI  - Proliferation of activated CD1d-restricted NKT cells is down-modulated by
      lymphocyte activation gene-3 signaling via cell cycle arrest in S phase.
AB  - Upon antigenic stimulation, CD1d-restricted NKT cells quickly secrete large
      amounts of cytokines. This prompt response demonstrates that CD1d-restricted NKT
      cells may potentially prove to be useful therapeutic agents for the treatment of
      many diseases. Despite the clinical importance of CD1d-restricted NKT cells, the
      regulating mechanisms of this unique T cell population remain to be defined. We
      found murine LAG-3 is inducible on CD1d-restricted NKT cells as the result of a
      variety of stimulants such as concanavalin A (con A) and anti-CD3. Also, antigen
      specific CD1d stimulation can elicit LAG-3 in CD1d-restricted NKT cells.
      Moreover, ectopic LAG-3 expression on CD1d-restricted NKT cells results in cell
      cycle arrest in the S phase. These results show that LAG-3 signaling on activated
      CD1d-restricted NKT cells may down-modulate NKT cell proliferation.

PMID- 17175183
TI  - Descriptive study comparing routine hospital administrative data with the
      Vascular Society of Great Britain and Ireland's National Vascular Database.
AB  - OBJECTIVE: To compare patient volume and outcomes in vascular surgery between an
      administrative data set (Hospital Episode Statistics) and a clinical database
      (National Vascular Database). DESIGN: Descriptive study. METHODS: Volume of cases
      determined by age, sex, year and procedure and in-hospital mortality by procedure
      for both datasets for patients undergoing either repair of abdominal aortic
      aneurysm, carotid endarterectomy or infrainguinal bypass over a three year period
      between 1st April 2001 and 31st March 2004. RESULTS: There were 32,242 admissions
      with a mention of the three selected vascular procedures within the
      administrative data set compared to 8462 within the clinical database. For NHS
      trusts common to both datasets, there were twice as many procedures (16,923)
      recorded within the administrative dataset compared to the clinical database.
      Patient characteristics were similar across both databases. Further analysis
      limiting the administrative data to records attributed to consultants known to
      contribute to the clinical database showed much closer agreement with only 11%
      more repairs of abdominal aortic aneurysm recorded within the administrative
      dataset compared to the National Vascular Database. CONCLUSIONS: There are
      significant differences in total numbers between HES and the NVD. If the National
      Vascular Database is to become a credible source of information on activity and
      outcomes for vascular surgery, there is a clear need to increase the number of
      contributing surgeons and to increase the completeness of data submitted. Further
      analysis at individual record level is needed to identify other reasons for
      discrepancies which could help to enhance data quality, both within Hospital
      Episode Statistics and within the National Vascular Database.

PMID- 17175184
TI  - Insomnia: pathophysiology and implications for treatment.
AB  - Interest in developing a greater understanding of the pathophysiogical mechanisms
      underlying primary insomnia has increased. Recent evidence indicates that there
      may be some neuroendocrine and clinical similarities between primary insomnia and
      major depressive disorder, that abnormal corticotropin releasing factor (CRF)
      activity occurs in major depression, and that CRF hyperactivity appears to
      mediate the hyperarousal seen in primary insomnia. These findings all point to
      the possibility of hypothalamic-pituitary-adrenal (HPA) axis and CRF overactivity
      in both disorders. More recent findings have strengthened the evidence that
      primary insomnia may be linked with mood disorders and is associated with HPA
      axis overactivity and excess secretion of CRF, adrenocorticotropin releasing
      hormone, and cortisol. These insights have implications for managing chronic
      primary insomnia, such as use of antiglucocorticoid agents.

PMID- 17175185
TI  - A novel gene cluster in Fusarium graminearum contains a gene that contributes to
      butenolide synthesis.
AB  - The development of expressed sequence tag (EST) databases, directed
      transformation and a sequenced genome has facilitated the functional analysis of
      Fusarium graminearum genes. Extensive analysis of 10,397 ESTs, derived from
      thirteen cDNA libraries of F. graminearum grown under diverse conditions,
      identified a novel cluster of eight genes (gene loci fg08077-fg08084) located
      within a 17kb region of genomic sequence contig 1.324. The expression of these
      genes is concomitantly up-regulated under growth conditions that promote
      mycotoxin production. Gene disruption and add-back experiments followed by
      metabolite analysis of the transformants indicated that one of the genes,
      fg08079, is involved in butenolide synthesis. The mycotoxin butenolide is
      produced by several Fusarium species and has been suggested, but not proven, to
      be associated with tall fescue toxicoses in grazing cattle. This is the first
      report of the identification of a gene involved in the biosynthetic pathway of
      butenolide.

PMID- 17175186
TI  - Update on the diagnosis of Haemophilus parasuis infection in pigs and novel
      genotyping methods.
AB  - Haemophilus parasuis causes Glasser's disease as well as a number of other
      diseases in pigs. The diagnosis of H. parasuis-associated disease is usually
      established by clinical signs, pathological findings and bacterial isolation but
      diagnosis is complicated by the existence of non-virulent strains and the early
      colonisation of the upper respiratory tract of healthy piglets. Moreover, several
      strains can be found on a farm and even within a single animal so it is important
      to determine the specific strain that is causing the clinical outbreak. Recently,
      genotyping methods have been developed with the goal of correlating genotype with
      the degree of virulence of H. parasuis strains. The association between genotype
      and virulence in H. parasuis is challenging due to the lack of knowledge of the
      complete genomic sequence and virulence factors of this bacterium.

PMID- 17175187
TI  - Spinal administration of a delta opioid receptor agonist attenuates hyperalgesia
      and allodynia in a rat model of neuropathic pain.
AB  - Neuropathic (NP) pain is a debilitating chronic pain disorder considered by some
      to be inherently resistant to therapy with traditional analgesics. Indeed, micro
      opioid receptor (OR) agonists show reduced therapeutic benefit and their long
      term use is hindered by the high incidence of adverse effects. However,
      pharmacological and physiological evidence increasingly suggests a role for
      deltaOR agonists in modulating NP pain symptoms. In this study, we examined the
      antihyperalgesic and antiallodynic effects of the spinally administered deltaOR
      agonist, d-[Ala(2), Glu(4)]deltorphin II (deltorphin II), as well as the changes
      in deltaOR expression, in rats following chronic constriction injury (CCI) of the
      sciatic nerve. Rats with CCI exhibited cold hyperalgesia and mechanical allodynia
      over a 14-day testing period. Intrathecal administration of deltorphin II
      reversed cold hyperalgesia on day 14 and dose-dependently attenuated mechanical
      allodynia. The effects of deltorphin II were mediated via activation of the
      deltaOR as the effect was antagonized by co-treatment with the delta-selective
      antagonist, naltrindole. Western blotting experiments revealed no changes in
      deltaOR protein in the dorsal spinal cord following CCI. Taken together, these
      data demonstrate the antihyperalgesic and antiallodynic effectiveness of a
      spinally administered deltaOR agonist following peripheral nerve injury and
      support further investigation of deltaORs as potential therapeutic targets in the
      treatment of NP pain.

PMID- 17175189
TI  - Erosive polyarthritis associated with Mycoplasma gateae in a cat.
AB  - Erosive polyarthritis was diagnosed in an 11-month-old neutered male Egyptian Mau
      cross cat with concurrent glucocorticoid-responsive dermatitis. Clinical signs,
      synovial fluid analysis, serological tests and radiographic appearance could not
      differentiate between immune-mediated and infective arthritis. Mycoplasma gateae
      was isolated by strictly anaerobic culture of the synovial fluid. Treatment with
      Enrofloxacin led to a rapid improvement of the cat's condition. Two months later
      the cat was euthanased because of severe glomerulonephritis and direct Coombs'
      test positive anaemia, possibly caused by mycoplasma infection. M gateae could
      not be isolated at post-mortem examination.

PMID- 17175188
TI  - Nonlinear magnetic field gradients can reduce SAR in flow-driven arterial spin
      labeling measurements.
AB  - This work describes how custom-built gradient coils, designed to generate
      magnetic fields with amplitudes that vary nonlinearly with position, can be used
      to reduce the potential for unsafe tissue heating during flow-driven arterial
      spin labeling processes. A model was developed to allow detailed analysis of the
      adiabatic excitation process used for flow-driven arterial water stimulation with
      elimination of tissue signal (FAWSETS) an arterial spin labeling method developed
      specifically for use in skeletal muscle. The model predicted that, by adjusting
      the amplitude of the gradient field, the specific absorption rate could be
      reduced by more than a factor of 6 while still achieving effective labeling. Flow
      phantom measurements and in vivo measurements from exercising rat hind limb
      confirmed the accuracy of the model's predictions. The modeling tools were also
      applied to the more widely used continuous arterial spin labeling (CASL) method
      and predicted that specially shaped gradients could allow similar reductions in
      SAR.

PMID- 17175190
TI  - Pansteatitis and severe hypocalcaemia in a cat.
AB  - A 13-year-old Siamese cat was presented for investigation of lethargy and
      progressive abdominal enlargement. Serum chemistry revealed severe reduction of
      total and ionised serum calcium. The omentum appeared hyperechoic with scattered
      hypoechoic foci on abdominal ultrasound examination. Elevated serum parathormone
      and low fractional excretion of calcium excluded a parathyroid disorder and renal
      loss of the electrolyte. During laparotomy the omentum appeared opaque, white and
      firm. Post-mortem examination revealed that the thoracic and subcutaneous fat was
      also affected. Histopathology confirmed the diagnosis of pansteatitis with
      diffuse calcium soaps formation. While, severe hypocalcaemia is occasionally seen
      in cats, the association with pansteatitis has not been reported previously. In
      man, a cause-and-effect relationship between calcium soaps and hypocalcaemia is
      recognised, though the association is rare.

PMID- 17175191
TI  - Effects of ultrasound on the reaction step of boric acid production process from
      colemanite.
AB  - Colemanite is one of the most important boron minerals used for production of
      boric acid. Boric acid (H(3)BO(3)) is produced by the reaction of colemanite
      (2CaO.3B(2)O(3).5H(2)O) with sulfuric acid in a heterogeneous solid-liquid
      reaction leading to crystallization of gypsum as a byproduct. The influence of
      ultrasound on the dissolution of colemanite in H(2)SO(4) solution and on the
      precipitation of the gypsum during the reaction was investigated. Experiments
      have been carried out in a batch stirred vessel at 85 degrees C in the absence
      and presence of ultrasound. The stirring rates were chosen as 600 rpm (for 500
      600 microm) and 800 rpm (for 1000-1180 microm) to provide a homogeneous
      suspension during the reaction. The boric acid and calcium ion concentrations in
      the solution were determined as a function of time. The results showed that
      ultrasound enhances the dissolution of colemanite and precipitation rate of the
      gypsum in the solution after 1h. It has been shown that the use of ultrasound
      decreases the size of gypsum crystals.

PMID- 17175193
TI  - The Plasmodium falciparum RhopH2 promoter and first 24 amino acids are sufficient
      to target proteins to the rhoptries.
AB  - The rhoptry secretory organelles of the malaria parasite, Plasmodium falciparum,
      contain a RhopH complex, which is composed of the proteins RhopH1, RhopH2, and
      RhopH3. RhopH1 is encoded by the rhoph1/clag multi-gene family, whereas RhopH2
      and RhopH3 are encoded by single-copy genes. The precise function of the RhopH
      complex has not been identified, but it has been shown that the component
      proteins are involved in erythrocyte binding and perhaps participate in the
      formation of the parasitophorous vacuolar membrane. In this study, we have
      isolated pfrhoph2 promoter plus the signal peptide encoding sequence and
      generated transgene expression constructs to evaluate a trafficking and the RhopH
      complex formation in transgenic P. falciparum parasite lines. Interestingly, we
      found that the N-terminal 24 amino acids of RhopH2, including signal peptide
      sequence, were sufficient to target GFP to the rhoptries under the rhoph2
      promoter. Because it was previously shown that the timing of the expression alone
      could not target proteins to the apical organelles, this targeting is likely
      mediated via a unique mechanism that is dependent on N-terminal 24 amino acids of
      RhopH2 early in the secretory pathway. The N-terminal one third of Clag3.1, which
      contains a distinct conserved domain with Toxoplasma gondii RON2, can not
      associate the RhopH complex as a GFP chimera, but a c-Myc-Clag3.1 chimera lacking
      the C-terminus successfully associates the RhopH complex indicating that
      cooperation of middle region is likely required but the C-terminus is not
      necessary.

PMID- 17175196
TI  - Easier, more effective, evidence-based guidelines for resuscitation:
      understanding the changes to the Australian Resuscitation Guidelines 2006.

PMID- 17175194
TI  - Heat shock protein 70 is translocated to lipid droplets in rat adipocytes upon
      heat stimulation.
AB  - In mammalian cells, lipid storage droplets contain a triacylglycerol and
      cholesterol ester core surrounded by a phospholipid monolayer into which a number
      of proteins are imbedded. These proteins are thought to be involved in modulating
      the formation and metabolic functions of the lipid droplet. In this study, we
      show that heat stress upregulates several heat shock proteins (Hsps), including
      Hsp27, Hsp60, Hsp70, Hsp90, and Grp78, in primary and differentiated adipocytes.
      Immunostaining and immunoblotting data indicate that among the Hsps examined,
      only Hsp70 is induced to redirect to the lipid droplet surface in heat-stressed
      adipocytes. The thermal induction of Hsp70 translocation to lipid droplet does
      not typically happen in a temperature- or time-dependent manner and occurs
      abruptly at 30-40 min and rapidly achieves a steady state within 60 min after 40
      degrees C stress of adipocytes. Though Hsp70 is co-localized with perilipin on
      the lipid droplets in stressed adipocytes, immunoprecipitation experiments
      suggest that Hsp70 does not directly interact with perilipin. Alkaline treatments
      indicate that Hsp70 associates with the droplet surface through non-hydrophobic
      interactions. We speculate that Hsp70 might noncovalently associate with
      monolayer microdomains of the lipid droplet in a manner similar to its
      interaction with lipid bilayer moieties composed of specific fatty acids. As an
      acute and specific cellular response to the heat stimulation, accumulation of
      Hsp70 on adipocytes lipid droplets might be involved in stabilizing the droplet
      monolayer, transferring nascent proteins to the lipid droplets, or chaperoning
      denatured proteins on the droplet for subsequent refolding.

PMID- 17175198
TI  - National program for depression associated with childbirth: the Australian
      experience.
AB  - Routine screening was introduced as a joint research/public-health initiative
      across 43 health services in Australia, funded by beyondblue, the National
      Australian Depression Initiative. This program included assessing risk factors
      and prevalence of depression in perinatal women. Other objectives included
      increasing awareness of the condition, training of relevant staff, and assessing
      the feasibility of a screening program. Women were screened antenatally and
      postnatally with a demographic questionnaire and the Edinburgh Postnatal
      Depression Scale. A subgroup of women and health professionals was surveyed. Over
      40,000 women participated directly in the program. Data and issues for specific
      groups are presented. There was a high level of acceptability to women and health
      professionals involved. Screening is acceptable and feasible as part of the
      mental-health management of perinatal women. It needs to be supplemented with
      information for women and education and support for staff.

PMID- 17175197
TI  - Lung carcinomas decrease the number of monocytes/macrophages (CD14+ cells) that
      produce TNF-alpha.
AB  - The role that inflammation plays in cancer is puzzling. In peripheral blood, TNF
      alpha-producing monocytes (CD14+ cells) were compared among patients with lung
      cancer, patients with tuberculosis and healthy donors; also, in pleural effusion
      TNF-alpha-producing CD14+ cells were compared between tuberculous patients and
      lung cancer patients. To analyze the level of the cellular alteration in TNF
      alpha production, an experimental model was set up. TNF-alpha-producing CD14+
      cells in peripheral blood from lung cancer patients were significantly lower than
      those from healthy donors. In pleural effusion, TNF-alpha-producing CD14+ cells
      were significantly lower in lung cancer patients than in tuberculous patients.
      Based on the results obtained from an experimental model, we suggest that this
      phenomenon was attributed to a reduced expression of TNF-alpha transcript. These
      findings provide evidence that lung carcinomas reduce TNF-alpha production by
      macrophages, possibly by inducing in these cells an M2 phenotype, which favor
      tumor progression.

PMID- 17175199
TI  - Psychological aspects of premenstrual syndrome.
AB  - Premenstrual syndrome (PMS) is a group of psychological and physical symptoms
      which regularly occur during the luteal phase of the menstrual cycle and resolve
      by the end of menstruation. The severe and predominantly psychological form of
      PMS is called premenstrual dysphoric disorder (PMDD). The exact aetiology of PMS
      is not known. PMS results from ovulation and appears to be caused by the
      progesterone produced following ovulation in women who have enhanced sensitivity
      to this progesterone. The increased sensitivity may be due to neurotransmitter
      (mainly serotonin) dysfunction. The key diagnostic feature is that the symptoms
      must be absent in the time between the end of menstruation and ovulation.
      Prospective symptom rating charts are used for this purpose. Treatment is
      achieved by suppression of ovulation or reducing progesterone sensitivity with
      selective serotonin re-uptake inhibitors. In this chapter, the authors describe
      the aetiology, symptoms, diagnosis and evidence-based management of premenstrual
      syndrome.

PMID- 17175200
TI  - Severe anaphylaxis to Gelofusine during a transthoracic echo bubble study.
AB  - We describe a severe anaphylactic reaction to Gelofusin, used as part of a
      transthoracic echo study on a middle-aged woman who had suffered a prior cerebral
      event.

PMID- 17175201
TI  - Report on the European Association of Echocardiography accreditations in
      echocardiography: December 2003-September 2006.
AB  - AIMS: The European Association of Echocardiography (EAE) launched its
      Accreditation scheme in echocardiography in December 2003. Currently there are
      accreditations in Adult Transthoracic Echocardiography and Transesophageal
      Echocardiography and an Accreditation in Echocardiography for Congenital Disease
      will be launched in December 2006. METHODS AND RESULTS: Over the past 3years 350
      applicants have undertaken the written exams and 157 applicants have completed
      the process and achieved accreditation. This report summarises the accreditation
      process, the details of the numbers of applicants and their progress through the
      Accreditation scheme. This report also provides data about the performance of the
      written exam, its reliability and the effectiveness of the questions and data
      about the reproducibility of the log book marking system. CONCLUSION: Taken
      together this report provides evidence that the EAE Accreditation schemes have
      been effective in establishing a standard for echocardiographic practice and an
      accreditation that is effectively organised, reliable, robust and successful.

PMID- 17175203
TI  - Sodium channel blockade may contribute to the analgesic efficacy of
      antidepressants.
AB  - Sodium channel blockers such as lidocaine, lamotrigine, and carbamazepine can be
      effective in the treatment of neuropathic pain. Though not approved for
      neuropathic pain indications, tricyclic antidepressants are often considered
      first-line treatment for conditions such as post-herpetic neuralgia and diabetic
      neuropathy. Several tricyclic antidepressants have been shown to block peripheral
      nerve sodium channels, which may contribute to their antihyperalgesic efficacy.
      In this study, we compared the sodium channel-blocking potency of a number of
      antidepressants, including tricyclic antidepressants and selective serotonin
      reuptake inhibitors. All compounds tested inhibited Na(V)1.7 in a state- and use
      dependent manner, with affinities for the inactivated state ranging from 0.24
      micromol/L for amitriptyline to 11.6 micromol/L for zimelidine. The tricyclic
      antidepressants were more potent blockers of Na(V)1.7. Moreover, IC(50)s for
      block of the inactivated state for amitriptyline, nortriptyline, imipramine,
      desipramine, and maprotiline were in the range of therapeutic plasma
      concentrations for both the treatment of depression as well as neuropathic pain.
      By contrast, fluoxetine, paroxetine, mianserine, and zimelidine had IC(50)s for
      Na(V)1.7 outside their therapeutic concentration ranges and generally were not
      efficacious against post-herpetic neuralgia or diabetic neuropathy. These results
      suggest that block of peripheral nerve sodium channels may contribute to the
      antihyperalgesic efficacy of certain antidepressants. PERSPECTIVE: Tricyclic
      antidepressants are often considered first-line treatment for neuropathic pain.
      Some tricyclic antidepressants block sodium channels, which may contribute to
      their antihyperalgesic efficacy. In the current study, we compared the potency of
      peripheral sodium channel blockade for several tricyclic antidepressants and
      selective serotonin reuptake inhibitors with their therapeutic efficacy.

PMID- 17175202
TI  - Quantitative sensory findings in patients with bortezomib-induced pain.
AB  - Bortezomib (PS-341) is a newly developed proteosome inhibitor that shows
      extremely promising antineoplastic effects against a variety of neoplasias.
      Neuropathic pain is emerging as a major complication of bortezomib. Although
      clinical reports have appeared in the literature describing the general symptoms
      of bortezomib chemoneuropathy, specific quantitative sensory data that detail the
      sensory deficits that might yield insight to the primary afferent dysfunction
      contributing to this pain is lacking. In this report, it is shown that patients
      with bortezomib-induced neuropathic pain have significantly elevated touch
      detection threshold and slotted peg board time, impaired sharpness detection, and
      elevated thresholds for the detection of skin warming and heat pain. Patients
      also had increased reports of cold pain. These data indicate that bortezomib
      induced neuropathy is associated with deficits in Abeta, Adelta, and C caliber
      primary afferent fibers. PERSPECTIVE: This work demonstrates that pain induced by
      the chemotherapy drug bortezomib is accompanied by dysfunction in all fiber types
      in sensory nerves. Impaired Abeta and C sensory function also extends into areas
      of skin that are not perceived as affected by pain.

PMID- 17175205
TI  - Characterization of the agr2 gene, a homologue of X. laevis anterior gradient 2,
      from the zebrafish, Danio rerio.
AB  - We characterized a zebrafish (Danio rerio) anterior gradient 2 homologue (agr2)
      gene. agr2 contains an open reading frame of 513bp encoding 171 amino acids.
      Deduced amino acid sequence comparison showed that the zebrafish agr2 protein
      shares high (80-89%) amino acid sequence similarity with those homologues of
      anterior gradient 2 (HAGR2, MAgr2, Tagr2, and Sagr2) from the human, mouse,
      pufferfish, and Atlantic salmon, while sharing less (67-71%) sequence similarity
      with those anterior gradient 2 genes (XAG-2, XAG-1, XAgr2, MAgr3, and HAGR3) from
      Xenopus laevis, mouse, and human. Both phylogenetic and syntenic analyses
      indicate that zebrafish agr2 is the orthologue of human AGR2 and mouse Agr2
      genes. Whole-mount in situ hybridization indicated that zebrafish agr2 is
      expressed in most organs, such as epidermis, olfactory bulbs, otic vesicles,
      pharynx, esophagus, pneumatic duct, swim bladder, and intestine, which contain
      mucus-secreting cells. Moreover, semi-quantitative RT-PCR demonstrated agr2 is
      expressed in the gill, pharynx/esophagus, swim bladder/pneumatic duct, and
      intestine in the adult fish. In contrast, Xenopus anterior gradient 2 homologues
      are mainly expressed in ectoderm-derived organs including the cement gland and
      otic vesicles, while human and mouse anterior gradient 2 orthologues are mainly
      distributed in endoderm-derived organs including the trachea, lungs, stomach,
      intestines, and colon.

PMID- 17175204
TI  - Expression profiles of Insulin-like growth factor binding protein-like 1 in the
      developing mouse forebrain.
AB  - Insulin-like growth factor binding protein-like 1 (IGFBPL-1) has a domain
      structure that resembles one in the insulin-like growth factor binding proteins
      (IGFBPs), which is a domain known to be bound by insulin-like growth factors
      (IGFs) with high affinity and to thereby affect cell growth and metabolism.
      However, the distribution and functions of IGFBPL-1 in the brain are not known.
      Thus, to clarify IGFBPL-1 expression profiles during development, we have
      investigated the expression patterns of IGFBPL-1 mRNA in developing mouse brains
      using in situ hybridization, focusing especially on the forebrain. On embryonic
      day (E)12, IGFBPL-1mRNA expressions were localized in the preplate of the
      neopallium, dorsal thalamus, the differentiating field of the epithalamus, and
      the hippocampus. On E14, strong expression was recognized in the subventricular
      zone (SVZ) and intermediate zone (IMZ) in the neopallium, hippocampus, the
      differentiating field of the epithalamus, and the dorsal thalamus. E14
      expressions were generally the strongest among all the stages examined and
      signals decreased thereafter. At E16 and E18, IGFBPL-1mRNA was strongly detected
      in the hippocampus and the SVZ of the neopallium. In postnatal stages, mRNA was
      found only in the granule cell layer of the dentate gyrus (DG). Notably, at P20,
      expression was restricted to the deep fraction of the granule cell layer, the
      location of late-born DG neurons.

PMID- 17175206
TI  - Simultaneous determination of 6 beta-blockers, 3 calcium-channel antagonists, 4
      angiotensin-II antagonists and 1 antiarrhythmic drug in post-mortem whole blood
      by automated solid phase extraction and liquid chromatography mass spectrometry.
      Method development and robustness testing by experimental design.
AB  - A method for the simultaneous determination of the beta-blockers atenolol,
      sotalol, metoprolol, bisoprolol, propranolol and carvedilol, the calcium-channel
      antagonists diltiazem, amlodipine and verapamil, the angiotensin-II antagonists
      losartan, irbesartan, valsartan and telmisartan, and the antiarrhythmic drug
      flecainide, in whole blood samples from forensic autopsies was developed. Sample
      clean-up was achieved by precipitation and solid phase extraction (SPE) with a
      mixed-mode column. Quantification was performed by reversed phase high
      performance liquid chromatography with positive electrospray ionization mass
      spectrometric detection (HPLC-MS). The method has been developed and robustness
      tested by systematically searching for satisfactory conditions using experimental
      designs including factorial and response surface designs. With the exception of
      amlodipine, the concentration limit of quantification (cLOQ) covered low
      therapeutic concentration levels for all the compounds. Within assay precisions
      and accuracies (bias) were 3.4-21% RSD and from -24 to 21% for the concentration
      range 1.00-5.00 microM, respectively. Between assay precisions were 4.4-28% RSD
      for the concentration range from 0.1 to 5 microM and recoveries varied from 9 to
      103%. The method is used for determination of cardiovascular drugs in post-mortem
      whole blood samples from forensic autopsy cases.

PMID- 17175207
TI  - Determination of the DNA methylation level of the marbled crayfish: an increase
      in sample throughput by an optimised sample preparation.
AB  - Using a previously described capillary electrophoretic method with laser-induced
      fluorescence detection the genomic methylation level can be determined exactly.
      We present a sample preparation that eliminates the surplus of fluorescence
      marker used for coupling resulting in an increase of sample throughput from 75 to
      250 analyses per week. The sensitivity of the method was also increased, which
      allows the determination of methylation levels under 1%. With these changes in
      sample preparation a methylation level of 1.64+/-0.03% in hepatopancreas DNA of
      the recently discovered marbled crayfish could be determined.

PMID- 17175208
TI  - Structural basis for the protective role of sulfite against transthyretin amyloid
      formation.
AB  - Transthyretin (TTR) is a plasma protein, which under conditions not yet
      completely understood, aggregates forming amyloid deposits that occur
      extracellularly. It is a protein composed of four identical subunits. Each
      monomer has a single cysteine residue (Cys10), which in the plasma is reduced
      (Cys-SH), oxidized (Cys-SO3-), sulfonated (Cys-S-SO3-) or bound to various
      sulfhydryls. There is evidence that these chemical modifications of the SH group
      alter the stability and the amyloidogenic potential of the protein. The
      sulfonated form was found to enhance the stability of the native conformation of
      TTR, avoiding misassembly of the protein leading to amyloid. Consequently, the
      potential treatment of TTR-type amyloidosis by sulfite has been suggested. The
      structure of TTR pre-incubated with sulfite at physiological pH, was determined
      by X-ray crystallography to provide structural insight for the stabilizing effect
      of sulfite. Each subunit has a beta-sandwich conformation, with two four stranded
      beta-pleated sheets (DAGH and CBEF) and a small alpha-helix between strands. The
      sulfonated cysteines have two sulfite oxygens involved in intramonomer hydrogen
      bonds that bridge Cys10, the amino acid immediately before beta-strand A, to the
      amino acids immediately after the edge beta-strand D. Implications of the newly
      observed interactions in the inhibition of fibril formation are discussed in
      light of the recent structural models of TTR amyloid fibrils.

PMID- 17175209
TI  - Geographic and other determinants of BMD change in European men and women at the
      hip and spine. a population-based study from the Network in Europe for Male
      Osteoporosis (NEMO).
AB  - INTRODUCTION: While the determinants of BMD change have been studied in women,
      there have been few longitudinal studies in men. As part of the Network in Europe
      for Male Osteoporosis (NEMO) study, data were analysed from 1337 men and 1722
      women aged 50-86y (mean=67 years) from 13 centres across Europe to assess
      determinants of BMD change and between-gender contrasts. METHODS: BMD was
      measured at the femoral neck, trochanter and/or L2-L4 spine on 2 occasions 0.8-8
      years apart (mean=3.5 years) using DXA densitometers manufactured by Hologic
      (n=6), Lunar (n=5) and Norland (n=2). Each was cross-calibrated using the
      European Spine Phantom and annual rates of BMD change (g/cm(2)/year) were
      calculated from the standardised paired BMD values. The EPOS risk factor
      questionnaire was administered at baseline. RESULTS: In multivariate linear
      regression models, there were large between centre differences in the mean rates
      of BMD change in all 3 sites for both genders (P<0.0001) with the standard
      deviation of the between centre heterogeneity in the adjusted means being 0.005
      g/cm(2)/year at the femoral neck. The overall adjusted mean annual rates of BMD
      change in g/cm(2)/year (95% CI) pooled across centres by random effects meta
      analysis in men were: femoral neck -0.005 (-0.009, -0.001); trochanter -0.003 (
      0.006, -0.001); and spine 0.000 (-0.004, 0.004). In women the respective
      estimates were: -0.007 (-0.009, -0.005); -0.004 (-0.006, -0.003); and -0.005 (
      0.008, -0.001). The I(2) statistic for heterogeneity was between 81% and 94%,
      indicating strong evidence of between centre heterogeneity. Higher baseline BMD
      value was associated with subsequent greater decline in BMD (P<0.001). Preserved
      BMD was associated with higher baseline body weight in all 3 sites in men
      (P<0.012) but not in women. Weight gain preserved BMD (P<0.039) in all 3 sites
      for both genders, except the male spine. Increasing age was associated with
      faster BMD decline at the trochanter in both genders (P<0.026) and with a slower
      rate of decline at the female spine (P=0.002). Effects of lifestyle, physical
      activity, medications, and reproductive factors were not consistent across sites
      or between genders. CONCLUSION: These results show major geographic variations in
      rates of BMD change in men and women over 50 years of age across diverse European
      populations and demonstrate that body weight and weight gain are key determinants
      of BMD change in men.

PMID- 17175210
TI  - Age-related changes in trabecular bone microdamage initiation.
AB  - With age, alterations occurring in bone quality, quantity, and microarchitecture
      affect the resistance of trabecular bone to local failure. The clinical
      implications of these changes are evident by the observed exponential increase in
      fracture incidence with age. Although age-related development of skeletal
      fragility is well established, it is unclear how the local failure properties of
      bone change with age. We previously reported a specimen-specific technique to
      assess microstructural stresses and strains associated with microdamage
      initiation but did not assess age-related changes. In this study, we compared
      younger (average age 2 years) and older (average age 10 years) bovine trabecular
      bone to evaluate how alterations in bovine bone quantity and quality with age
      affect the local mechanical environment associated with microdamage formation.
      The results show strong positive correlations between microdamage and local
      stresses and strains for both younger and older bovine trabecular bone.
      Correlation strength was slightly improved (<8%) for some parameters by
      incorporating heterogeneous local material properties based on mineral density
      into the finite element models. Within individual trabeculae, average stresses
      and strains were significantly higher in microdamaged trabeculae compared to
      randomly selected undamaged trabeculae, regardless of age. However, damaged
      trabeculae in older bone were found to have higher stresses and lower strains
      than those from younger bone. Corresponding differences in mineral density,
      microarchitecture, and FEM-determined local material properties were also
      observed between the two groups. Taken together, these data suggest marked age
      related changes in the mechanics of microdamage initiation at the trabecular
      level. The combined experimental, computational, and histochemical approaches
      used in this study provide an improved understanding of microdamage initiation
      and bone quality.

PMID- 17175212
TI  - Healing of an ulnar defect using a proprietary TCP bone graft substitute, JAX, in
      association with autologous osteogenic cells and growth factors.
AB  - Currently, available synthetic bone substitutes have adequate osteoconductive
      properties but have little or no osteoinductivity. Recent research has focused on
      using osteogenic growth factors or cells to provide this. JAX is a beta
      tricalcium phosphate bone graft substitute that has a novel shape and
      interlocking design. This study investigated delivery methods and the use of
      autologous cell therapy to enhance healing of a bone defect using JAX as a
      scaffold. Bone marrow was harvested from 24 New Zealand White rabbits. The
      mononuclear cell fraction was isolated and culture expanded. Bilateral 1.5 cm
      defects in the ulna were filled with: Group 1: JAX alone, Group 2: JAX plus
      1x10(7) autologous BMSCs injected at the time of surgery, Group 3: JAX plus
      8x10(6) autologous BMSCs cultured on granules for 14 days prior to surgery, Group
      4: JAX plus fresh bone marrow (BMA), Group 5: cortical autograft, Group 6: JAX
      plus 2.5 microg VEGF. Radiographs demonstrated that there was more new bone in
      the BMA and VEGF groups compared to JAX alone. Groups containing autologous BMSCs
      were only slightly better than JAX alone in the amount of bone in the defect but
      did improve bridging of the osteotomy. Histomorphometry identified a significant
      increase in bone volume in the BMA group compared to JAX alone. BMA and VEGF
      enhanced healing of bone defects whereas expanded BMSCs provided little advantage
      over scaffold alone. There was no difference between delivery methods of
      autologous BMSCs. These observations suggest that the provision of osteogenic
      cells alone is insufficient to enhance bone healing and that additional factors
      are required to initiate this process in vivo.

PMID- 17175211
TI  - Effect of mechanical stimuli on skeletal regeneration around implants.
AB  - Due to the aging population and the increasing need for total joint replacements,
      osseointegration is of a great interest for various clinical disciplines. Our
      objective was to investigate the molecular and cellular foundation that underlies
      this process. Here, we used an in vivo mouse model to study the cellular and
      molecular response in three distinct areas of unloaded implants: the periosteum,
      the gap between implant and cortical bone, and the marrow space. Our analyses
      began with the early phases of healing, and continued until the implants were
      completely osseointegrated. We investigated aspects of osseointegration ranging
      from vascularization, cell proliferation, differentiation, and bone remodeling.
      In doing so, we gained an understanding of the healing mechanisms of different
      skeletal tissues during unloaded implant osseointegration. To continue our
      analysis, we used a micromotion device to apply a defined physical stimulus to
      the implants, and in doing so, we dramatically enhanced bone formation in the
      peri-implant tissue. By comparing strain measurements with cellular and molecular
      analyses, we developed an understanding of the correlation between strain
      magnitudes and fate decisions of cells shaping the skeletal regenerate.

PMID- 17175215
TI  - Expression changes in tolerant murine cardiac allografts after gene therapy with
      a lentiviral vector expressing alpha1,3 galactosyltransferase.
AB  - Comparison of intragraft gene expression changes in tolerant cardiac allograft
      models may provide the basis for identifying pathways involved in graft survival.
      Our laboratory has previously demonstrated that tolerance to the gal alpha1,3 gal
      epitope, the major target of rejection of wild-type pig hearts in human cardiac
      transplantation, can be achieved after transplantation with bone marrow
      transduced with a lentiviral vector expressing alpha1,3 galactosyltransferase. We
      now present intracardiac gene expression changes associated with long-term
      tolerance in this model. Biotin-labeled cRNA was hybridized to Affymetrix
      GeneChip 430 2.0 Mouse Genome Arrays. Data were subjected to functional
      annotation analysis to identify genes of known function in which expression was
      increased or decreased by at least 2-fold (t-test, P < .05) in tolerant gal+/+
      wild-type hearts as compared to transplanted syngeneic controls. Tolerant hearts
      demonstrated increased expression of genes associated with the stress response,
      modulation of immune function and cell survival (HSPa9a, CD56, and Akt1s1), and
      decreased expression of several immunoregulatory genes (CD209, CD26, and PDE4b).
      These data suggest that tolerance may be associated with activation of
      immunomodulatory and survival pathways.

PMID- 17175214
TI  - T-cell depletion eliminates the development of cardiac allograft vasculopathy in
      mice rendered tolerant by the induction of mixed chimerism.
AB  - We previously demonstrated that cardiac allografts to fully tolerant chimeric
      mice developed cardiac allograft vasculopathy (CAV). Here we begin to examine
      which components of the immune system are responsible for the pathogenesis of CAV
      in such tolerant recipients. B10.A/B6 mixed chimeric mice were created by
      receiving injections of bone marrow cells from B10.A (H-2k) mice given to C57BL/6
      (B6; H-2b) mice with some preparations. B10.A skin grafts were first placed onto
      B10.A/B6 mixed chimeric recipients. When the donor strain skin grafts had
      survived perfectly for at least 56 days, B10.A hearts were transplanted
      heterotopically into B10.A/B6 mixed chimeric recipients. Hearts were examined for
      the presence of CAV 56 days later. To determine the effector cells that
      contribute to the development of CAV, they were treated weekly with a combination
      of anti-CD4/CD8 monoclonal antibodies (mAbs) or anti-NK1.1 mAb continuing until
      56 days. 14 B10.A cardiac transplants of 18 otherwise untreated B10.A/B6 chimeric
      recipients developed CAV; concurrent B6 isografts were unaffected (0/7). In
      chimeric recipients treated with anti-CD4/8 mAbs, the prevalence of CAV was
      greatly reduced (0/6, P < .01 compared to the untreated group). Anti-NK1.1 mAb
      was not effective in the prevention of CAV (4/5). These data suggest that T cells
      may contribute in some way to the development of CAV that occurs in those fully
      tolerant recipients. Host T cells that may still be responsive to non-major
      histocompatability complex antigens, including tissue-specific antigens presented
      not on skin but on heart, may also be responsible for the development of CAV in
      tolerant animals.

PMID- 17175216
TI  - Regulation of donor T cells in the tolerant rats to graft-versus-host disease by
      FTY720 following small bowel transplantation.
AB  - AIMS: The potency of immunosuppression is a critical factor in small bowel
      transplantation (SBTx). FTY720 altered lymphocyte trafficking and prevented the
      donor T cells from migrating into target organs, resulting in the prolongation of
      recipient survival in acute graft-versus-host disease (GVHD) of SBTx. However,
      the effect of FTY720 on donor T cells in the chronic phase of GVHD following SBTx
      remains unclear. METHODS: Heterotopic SBTx was performed in a WF-to-F1 (WF x ACI)
      rat combination. Recipients were given FTY720 for 14 days after SBTx. The
      subpopulations of donor-derived T cells and the cytokine production in the target
      tissues were evaluated on postoperative day 150. RESULTS: FTY720 treatment
      significantly prolonged recipient survival over 150 days without any clinical
      signs of GVHD. The numbers of donor-derived CD4+ and CD8+ T cells in the
      peripheral blood, mesenteric lymph nodes, and Peyer's patches of recipients were
      maintained at low levels on postoperative 150, which were almost similar to the
      levels on postoperative day 14. In the host lamina propria, however, a
      significant higher number of donor T cells (CD4+, 18.4 +/- 4.3 x 10(4); CD8+,
      13.9 +/- 3.6 x 10(4)) were still observed on postoperative day 150. Production of
      interferon-gamma was significantly reduced in target tissues by FTY720 treatment
      both in the acute and chronic phase. However, interleukin-4 and interleukin-10
      production, which was significantly higher on day 14, returned to the level of
      naive rats in the chronic phase. CONCLUSIONS: A 14-day treatment of FTY720
      induced tolerance in our SBTx model. Down-regulation of both Th1 and Th2 immune
      response was observed in the chronic phase.

PMID- 17175217
TI  - Permanent, lowered HLA class I expression using lentivirus vectors with shRNA
      constructs: Averting cytotoxicity by alloreactive T lymphocytes.
AB  - Transplantation of many tissues requires histocompatibility matching of human
      leukocyte antigens (HLA) to prevent graft rejection, to reduce the level of
      immunosuppression needed to maintain graft survival, and to minimize the risk of
      graft-versus-host disease, particularly in the case of bone marrow
      transplantation. However, recent advances in fields of gene delivery and genetic
      regulation technologies have opened the possibility of engineering grafts that
      display reduced levels of HLA expression. Suppression of HLA expression could
      help to overcome the limitations imposed by extensive HLA polymorphisms that
      restrict the availability of suitable donors, necessitate the maintenance of
      large donor registries, and complicate the logistics of procuring and delivering
      matched tissues and organs to the recipient. Accordingly, we investigated whether
      knockdown of HLA by RNA interference (RNAi), a ubiquitous regulatory system that
      can efficiently and selectively inhibit the expression of specific gene products,
      would enable allogeneic cells to evade immune recognition. For efficient and
      stable delivery of short hairpin-type RNAi constructs (shRNA), we employed
      lentivirus-based gene transfer vectors, which provide a delivery system that can
      achieve integration into genomic DNA, thereby permanently modifying transduced
      graft cells. Our results show that lentivirus-mediated delivery of shRNA
      targeting pan-Class I and allele-specific HLA can achieve efficient and dose
      dependent reduction in surface expression of HLA in human cells, associated with
      enhanced resistance to alloreactive T lymphocyte-mediated cytotoxicity, while
      avoiding MHC-non-restricted killing. We hypothesize that RNAi-induced silencing
      of HLA expression has the potential to create histocompatibility-enhanced, and,
      eventually, perhaps "universally" compatible cellular grafts.

PMID- 17175218
TI  - Effect of immature dendritic cell injection before heterotropic cardiac
      allograft.
AB  - Although dendritic cells (DCs) are unrivaled for initiation of immune responses,
      the immunomodulatory capacity of chemically fixed DC has not been thoroughly
      evaluated. We monitored the tolerogenic capacity of chemically fixed DCs using
      allogeneic heart transplantations. Bone marrow progenitors were differentiated
      into immature DCs which were then chemically fixed and injected intravenously
      into recipient mice at 14 days before allogeneic heart transplantation.
      Chemically fixed DCs markedly prolonged graft survival in the major
      histocompatibility complex (MHC) I/II mismatch cardiac transplantation (B6 -->
      B10.A; median survival time [MST] 12.5 days vs >70 days). T cells that
      encountered chemically fixed DCs showed attenuated apoptotic cell death and
      inactivated phenotypes after allogeneic heterotropic heart transplantation.
      Furthermore, when DCs from interleukin (IL)-10-/- mice were treated, the in vitro
      T-cell response was greater than that from IL-12-/- mice. We have suggested that
      the chemically fixed DCs may mediate peripheral T-cell tolerance, with
      therapeutic potential for allogeneic transplantation.

PMID- 17175219
TI  - Induction of accommodation model by combined RNA interference targeting 1,3
      galactosyltransferase gene and low-dose GS-IB4 lectin in vitro.
AB  - OBJECTIVE: This study sought to mimic the interaction of xenograft endothelial
      cells and human serum in vitro after successfully silencing the expression of
      porcine alpha1,3-galactosyltransferase (alpha1,3GT) gene by RNA interference
      (RNAi), and to investigate the possibility of inducing accommodation in vitro by
      stimulation of alpha-Gal-specific binding lectin, Griffonia simplicifolia
      isolectin B4 (GS-IB4) and RNAi. MATERIALS AND METHODS: Various alpha-Gal
      expression patterns on a pig endothelial cell immortalized line (PED) was
      achieved by serial doses of small interfering RNA (siRNA) targeting porcinc
      alpha1,3GT gene. alpha1,3GT-siRNA transfected PEDs were exposed to increasing
      doses of GS-IB4 lectin (0.5, 2, and 8 microg/mL) for 4 hours before incubation
      with normal human serum (NHS). Accommodation phenomenon of PEDs in NHS was
      observed by 51Cr release and antibody/complement binding assays. RESULTS: With
      combined RNAi and low-dose GS-IB4 stimulation, PEDs remarkably inhibited
      complement-mediated cytotoxicity, which showed a better protective effect than
      using RNAi alone. At a concentration of 2 mug/mL, GS-IB4 exhibited the maximum
      protective effect. The expression of E-selectin on alpha1,3GT-siRNA transfected
      PEDs did not differ from that on parental PEDs with heat-inactivated NHS (HINHS)
      stimulation. Combined with GS-IB4 stimulation, however, it inhibited expression
      of E-selectin, which was GS-IB4 dose dependent, resulting in mean fluorescence
      intensity values of 98.5, 42.0, and 36.3 at 0.5, 2, and 8 microg/mL. The mRNA
      expression of the protective gene HO-1 was significantly up-regulated after
      treatment with RNAi and low-dose of GS-IB4. CONCLUSIONS: Combined RNAi and low
      dose GS-IB4 induced pig endothelial cell accommodation in vitro. The level of
      alpha-Gal expression played an important role in the induction of accommodation.

PMID- 17175220
TI  - Effects of tolerance induction on the actions of interferon-gamma on porcine
      cardiac allografts.
AB  - It is well known that interferon-gamma (IFN-gamma) not only plays a critical role
      in antigen-dependent but also in antigen-independent tissue injury; however, it
      is not clear how tolerance induction affects the actions of IFN-gamma in the
      transplant setting. To address this question, we compared the effects of IFN
      gamma on porcine recipients of near-syngeneic, rejecting, and tolerant heart
      transplants. IFN-gamma was infused continuously into the left anterior descending
      artery of hearts transplanted into 3 groups of major histocompatibility complex
      (MHC) inbred miniature swine, each treated with a 12-day course of cyclosporine A
      (CyA). Group 1 recipients received a MHC class I disparate heart, group 2
      recipients received a near-syngeneic heart, and group 3 recipients were
      cotransplanted with a MHC class I disparate heart and kidney, which uniformly
      induces tolerance to both grafts. An additional group of animals was not
      transplanted but received intracoronary IFN-gamma infusion into their native
      hearts. IFN-gamma perfusion not only accelerated the acute rejection of MHC class
      I disparate hearts (mean survival time = 19 +/- 7.21 vs 38 +/- 8.19 days, P =
      .025), but caused near-syngeneic heart transplants, which otherwise survive
      indefinitely, to reject within 35 days (n = 3). In contrast, IFN-gamma perfusion
      had no demonstrable effects on interstitial rejection, the development of
      vascular lesions, or graft survival in tolerant heart plus kidney allograft
      recipients (n = 4) or in autologous hearts (n = 2). These results suggest that
      tolerance induction mitigates the damaging effects of IFN-gamma itself and that
      the beneficial effects of tolerance induction on acute and chronic rejection may
      extend to antigen-independent factors like ischemia/reperfusion injury.

PMID- 17175221
TI  - Adoptive cell therapy using in vitro generated human CD4+ CD25+ regulatory t
      cells with indirect allospecificity to promote donor-specific transplantation
      tolerance.
AB  - The holy grail in clinical transplantation is the establishment of long-term
      donor-specific transplantation tolerance with the minimum use of
      immunosuppressive agents. CD4+ CD25+ regulatory T cells (Tregs) play a crucial
      role in the prevention of autoimmunity, and appear to mediate transplantation
      tolerance. Harnessing Tregs for potential adoptive cell therapy to promote donor
      specific transplantation tolerance is promising. Here we show that human CD4+
      CD25+ Tregs with indirect allospecificity for an HLA-A2 (103-120) peptide can be
      generated from purified peripheral blood CD4+ CD25+ by priming with HLA-DR0101+
      A2- autologous dendritic cells (DCs) pulsed with the A2 peptide in vitro. The
      antigen specificity for the A2 peptide was demonstrated in functional assays and
      flow cytometric analysis using a fluorescent tetramer composed of HLA-DR0101 and
      the A2 peptide. The CD4+ CD25+ Tregs with indirect allospecificity for the A2
      peptide showed potent suppression of an indirect alloresponse by effector CD4+
      CD25- T-helper cells. Importantly, the selected CD4+ CD25+ Tregs can be expanded
      substantially to meet a therapeutic end after T-cell receptor (TCR) stimulation
      by CD3/CD28 antibody-coated beads in the presence of high doses of interleukin-2
      (IL-2). The expanded CD4+ CD25+ Tregs highly expressed Foxp3, and retained their
      suppressive properties and maintained expression of lymphoid homing receptor
      CD62L. Taken together, these data pave the way for clinical studies using in
      vitro generated and expanded human CD4+ CD25+ Tregs with indirect allospecificity
      as therapeutic reagents to promote donor-specific transplantation tolerance.

PMID- 17175222
TI  - FOXP3-positive regulatory cells inside the allograft and the correlation with
      rejection.
AB  - BACKGROUND: Foxp3 is a transcription factor associated with regulatory T cells.
      Little is known about the role of Foxp3+ regulatory T cells in relation to graft
      rejection in humans. METHODS: By using a quantitative polymerase chain reaction
      assay, we measured the levels of messenger RNA (mRNA) for Foxp3 in 27 samples
      obtained at allograft nephrectomy for acute nonvascular rejection (ANVR; n = 7),
      or acute vascular rejection (AVR; n = 15), or loss due to a nonimmune cause
      (LNIC; n = 5, as control). Granzyme B was also analyzed as a positive control for
      the host-driven immune response. RESULTS: Median Foxp3 mRNA levels correlated
      with the severity of rejection: LNIC 1.000, ANVR 1.429, and AVR 3.904 (P = .022
      for LNIC and AVR by the Kruskal-Wallis test). The receiver operating
      characteristic curve for AVR demonstrated an area under the curve of 0.733 (P =
      .04; 95% CI, 0.528-0.939). The levels of granzyme B mRNA also showed the same
      profile but did not reach statistical significance. CONCLUSIONS: The presence of
      mRNA for Foxp3 inside the graft suggested specific homing during severe episodes
      of acute rejection. Its presence may indicate the development of host
      immunoregulatory responses during the ongoing cytolytic activity. In addition,
      assessment of Foxp3 mRNA inside the graft may distinguish vascular from
      nonvascular rejection.

PMID- 17175223
TI  - The role of Foxp3+ regulatory T cells in liver transplant tolerance.
AB  - The liver has long been considered a tolerogenic organ that favors the induction
      of peripheral tolerance. The mechanisms underlying liver tolerogenicity remain
      largely undefined. In this study, we characterized Foxp3-expressing CD4+ CD25+
      regulatory T cells (Treg) in liver allograft recipients and examined the role of
      Treg in inherent liver tolerogenicity by employing the mouse spontaneous liver
      transplant tolerance model. Orthotopic liver transplantation was performed from
      C57BL/10 (H2b) to C3H/HeJ (H2k) mice. The percentage of CD4+ CD25+ Treg was
      expanded in the liver grafts and recipient spleens from day 5 up to day 100
      posttransplantation, associated with high intracellular Foxp3 and CTLA4
      expression. Immunohistochemistry further demonstrated significant numbers of
      Foxp3+ cells in the liver grafts and recipient spleens and increased transforming
      growth factor beta expression in the recipient spleens throughout the time
      courses. Adoptive transfer of spleen cells from the long-term liver allograft
      survivors significantly prolonged donor heart graft survival. Depletion of
      recipient CD4+ CD25+ Treg using anti-CD25 monoclonal antibody (250 microg/d)
      induced acute liver allograft rejection, associated with elevated anti-donor T
      cell proliferative responses, CTL and natural killer activities, enhanced
      interleukin (IL)-2, interferon-gamma, IL-10, and decreased IL-4 production, and
      decreased T-cell apoptotic activity in anti-CD25-treated recipients. Moreover,
      CTLA4 blockade by anti-CTLA4 monoclonal antibody administration exacerbated liver
      graft rejection when combined with anti-CD25 monoclonal antibody. Thus, Foxp3+
      CD4+ CD25+ Treg appear to underpin spontaneous acceptance of major
      histocompatability complex- mismatched liver allografts in mice. CTLA4, IL-4, and
      apoptosis of alloreactive T cells appear to contribute to the function of Treg
      and regulation of graft outcome.

PMID- 17175224
TI  - Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance.
AB  - Liver allografts are accepted spontaneously in all mouse strain combinations
      without immunosuppressive therapy. The mechanisms underlying this phenomenon
      remain largely undefined. In this study, we examined the effect of CD4+ CD25+ T
      regulatory cells (Treg) on the induction of mouse liver transplant tolerance.
      Orthotopic liver transplantation was performed from B10 (H2b) to C3H (H2k) mice.
      Depleting rat anti-mouse CD25 mAb (PC61) was given to the donors or recipients
      (250 microg/d IP) pretransplant or to the recipients postoperatively. At day 5
      posttransplantation, both effector T cells (mainly CD8) and CD4+ CD25+ Treg were
      increased in the liver allografts and host spleens compared to naive mice. Anti
      CD25 mAb administration, either pretransplantation or posttransplantation,
      reduced the ratio of CD4+ CD25+ Treg to the CD3 T cells of liver grafts and
      recipient spleens and induced liver allograft acute rejection compared to IgG
      treatment. Anti-CD25 mAb administration elevated anti-donor T-cell proliferative
      responses and CTL and NK activities of graft infiltrates and host splenocytes;
      reduced CTLA4, Foxp3, and IDO mRNA levels; increased IL-10 and IFN-gamma; and
      decreased IL-4 mRNA levels in the livers or host spleens. The number of apoptotic
      T cells was reduced significantly in the liver grafts and treated host spleens.
      Therefore, anti-CD25 mAb administration changed the balance of CD4+ CD25+ Treg to
      activated T cells of liver graft recipients, preventing liver transplant
      tolerance. This was associated with enhanced anti-donor immune reactivity,
      downregulated Treg gene expression, and reduced T cell apoptosis in the grafts
      and host spleens.

PMID- 17175225
TI  - Protective effect of prostaglandin E2 receptors EP2 and EP4 in alloimmune
      response in vivo.
AB  - Prostaglandin E2 (PGE2) is produced during inflammatory responses mediating a
      variety of both innate and adaptive immune responses through 4 distinct
      receptors: EP1 to EP4. The use of gene-targeted mice and selective
      agonists/antagonists responsible for each receptor has gradually revealed that
      each receptor plays a unique and important role in various disease conditions. In
      addition, PGE2 is known to have some immunosuppressive properties. In this study,
      we investigated the role of PGE2 receptors by examining the therapeutic efficacy
      of highly selective receptor agonists on the alloimmune response in vivo. We used
      a fully major histocompatibility complex (MHC)-mismatched murine cardiac
      transplantation model. C57BL/6 cardiac allografts were heterotopically
      transplanted into BALB/c recipients. We treated mice with a highly selective
      agonist for each EP receptor. EP2 and EP4 agonists significantly prolonged
      allograft survival compared with controls. In particular, the EP4 agonist was
      more effective than the EP2 agonist in the inhibition of acute allograft
      rejection. In conclusion, PGE2 receptors merit further study as novel
      therapeutics for clinical transplantation.

PMID- 17175226
TI  - Immunoregulation and apoptosis induction of nitric oxide in the human mixed
      lymphocytes culture.
AB  - Nitric oxide (NO) is a multifunctional molecule in a variety of physiologic and
      pathologic processes. Its precise effect on human T lymphocyte responses against
      alloantigens are not yet fully known, although it has been reported that NO is
      antiproliferative and can cause apoptosis in several cell types. To address these
      issues, we analyzed the effects of an NO donor on mixed lymphocyte cultures (MLC)
      and on apoptosis induction in T lymphocytes activated with alloantigens. NOC 18
      was used as an NO donor. The MLC was performed with human peripheral blood
      mononuclear cells isolated from healthy volunteers. Cell division and interleukin
      (IL)-2 production were measured with CFSE labeling and an EIA kit, respectively.
      After cells were incubated with NOC 18 for 24 hours, DNA fragmentation was
      assessed using the diphenylamine assay. Pre-culture of cells with NOC 18 for 24
      hours resulted in significant inhibition of cell proliferation and IL-2
      production in MLC. NOC 18 induced DNA fragmentation of cells harvested from an
      MLC following 7 days of the culture, in a dose-dependent manner, whereas it never
      exerted any influence on DNA fragmentation of freshly isolated cells. A chemical
      NO donor, NOC-18, may have immunosuppressive ability when treatment of responder
      cells occurs before the beginning of the MLC and may induce apoptosis of
      alloantigen-activated T lymphocytes.

PMID- 17175227
TI  - Cytomegalovirus accelerates chronic allograft nephropathy in a rat renal
      transplant model with associated provocative chemokine profiles.
AB  - BACKGROUND: Studies have shown that rat cytomegalovirus (RCMV) infection
      accelerates transplant vascular sclerosis (TVS) in rat heart and small bowel
      allotransplants. In these models, RCMV-accelerated TVS results from increased
      graft infiltration of inflammatory cells through up-regulation of chemokine
      expression. The aim of this study was to determine if RCMV infection accelerates
      renal transplant chronic allograft nephropathy (CAN), and the role of chemokines
      in this process. METHODS: F344 kidneys were transplanted into Lewis recipients
      with and without RCMV infection. To monitor CAN, serum creatinine (Cr) levels
      were measured starting at 4 weeks posttransplantation. At 7 and 21 days, and at
      terminal rejection, grafts were examined for histologic changes, inflammatory
      cell infiltrates, viral load, and chemokine expression profiles. RESULTS: By week
      8, serum Cr showed significant elevation (P < .01) in the RCMV-infected group vs
      uninfected group, and remained significantly elevated through the end of the
      study. RCMV+ renal allografts had significant inflammatory cell infiltration and
      increased CAN at postoperative day (POD) 28. The CC chemokines RANTES, MCP-1, and
      MIP-1alpha, and the CXC chemokine IP-10 were up-regulated in RCMV-infected vs
      uninfected allografts. IP-10 was significantly up-regulated early in the process,
      whereas RANTES and MCP-1 were induced at a later time. CONCLUSIONS: RCMV
      infection accelerates CAN, with associated graft inflammatory infiltrates, which
      is paralleled by an increase in expression of CC and CXC chemokines. Our findings
      suggest that the early induction of IP-10 in the infected allografts promotes
      alterations in T-cell and monocyte migration to the graft, which initiates
      accelerated inflammatory and fibrotic changes associated with CAN.

PMID- 17175228
TI  - Role of CXCR3 and CCR5 in allograft rejection.
AB  - Chemokines are known to participate in allograft rejection by mediating leukocyte
      trafficking. Despite redundancy in chemokine family, several chemokine-chemokine
      receptor interactions have proven critical in alloimmune responses. We sought to
      determine the effect of combined blockade of CXCR3 and CCR5, two critical
      chemokine receptors, in acute rejection. METHODS: Heterotopic heart
      transplantation was performed using BALB/c to B6/129 mice deficient in CCR5.
      Following transplantation these mice were treated with goat anti-CXCR3 serum
      every other day. In the control group, BALB/c hearts were transplanted in wild
      type B6/129 recipients and treated with goat serum alone. No immunosuppression
      was given to either group. Recipient mice were then assessed daily for allograft
      function by abdominal palpation, and graft survival was confirmed by laparotomy.
      RESULTS: The donor hearts in the control group were rejected at 6 +/- 1 days
      posttransplantation. Combined blockade of CXCR3 and CCR5 prolonged allograft
      survival versus control; all allografts survived to 24 days. In addition, there
      was a decrease in graft infiltrating CD4 and CD8 lymphocytes in the experimental
      group at 24 days. CONCLUSION: Combined CXCR3 and CCR5 blockade is effective in
      prolonging allograft survival in a fully MHC mismatched murine model. Combined
      chemokine blockade holds promise in control of acute rejection in organ
      transplantation.

PMID- 17175230
TI  - Adenovirus-mediated antisense-ERK2 gene therapy attenuates chronic allograft
      nephropathy.
AB  - BACKGROUND: The aim of this study was to investigate the effects of adenovirus
      mediated antisense ERK2 (Adanti-ERK2) gene therapy on chronic allograft
      nephropathy. METHODS: We employed a rat kidney transplantation mode (F344-
      >Lewis) and studied four groups: (1) controls (n = 6); (2) vector controls (n =
      6); (3) an Adanti-ERK2 group (n = 10); and (4) an isograft group (n = 4). The
      animals were monitored for proteinuria, graft histology, infiltrating cells, and
      immune-related gene (interleukin-2 [IL-2] and intracellular adhesion molecule-1
      [ICAM-1]) expression for 20 weeks after transplantation. RESULTS: The control
      group had increasing proteinuria during the 20-week follow-up. All rats showed
      advanced chronic renal failure associated with strong immune cell infiltration
      and immune gene expression. Chronic graft injury was accelerated in the vector
      control group, but no significant difference was observed compared with the
      control group. In contrast, the Adanti-ERK2 group showed less inflammation and
      improved graft histology/function compared with controls. Moreover, ERK2 protein
      expression in the Adanti-ERK2 group was lower than in the control group (P < .05)
      and vector-control group (P < .05). Furthermore, serial estimates of genes (IL-2,
      ICAM-1) related to chronic rejection showed significant downregulation in the
      Adanti-ERK2 group (P < .01). CONCLUSIONS: Adenovirus-mediated antisense ERK2 gene
      therapy attenuated chronic allograft nephropathy. The protective effects of
      antisense ERK2 gene therapy may have derived from a blocked ERK signal
      transduction pathway, which reduced ERK expression as well as those of immune
      related genes.

PMID- 17175229
TI  - The universal NF-kappaB inhibitor a20 protects from transplant vasculopathy by
      differentially affecting apoptosis in endothelial and smooth muscle cells.
AB  - Transplant vasculopathy (TV) is an accelerated form of atherosclerosis resulting
      in chronic rejection of vascularized allografts. The causes of TV are
      multifactorial and integrate at the level of the vascular wall, leading to a
      phenotypic switch of endothelial cells (ECs) and smooth muscle cells (SMCs). A20
      is a NF-kappaB-dependent stress response gene in ECs and SMCs with potent anti
      inflammatory effect in both cell types through blockade of NF-kappaB. A20
      expression in ECs and SMCs correlates with the absence of TV in rat kidney
      allografts and long-term functioning human kidney allografts. We demonstrate that
      A20 protects ECs from tumor necrosis factor, Fas, and natural killer cell
      mediated apoptosis by inhibiting proteolytic cleavage of caspase 8. A20 also
      safeguards ECs from complement-mediated necrosis. Hence, effectively shutting
      down cell death pathways initiated by inflammatory and immune offenders
      associated with TV. In contrast, A20 sensitizes SMCs to cytokine and Fas-mediated
      apoptosis through a novel nitric oxide (NO)-dependent mechanism. The unexpected
      proapoptotic effect of A20 in SMCs translates in vivo by the regression of
      established neointimal carotid lesions following balloon angioplasty in rats.
      Antedating apoptosis of SMCs, expression of the inducible NO synthase increases
      in A20-expressing neointimal SMCs, corroborating the involvement of NO in causing
      the proapoptotic effect of A20 in SMCs. Combined anti-inflammatory and anti- or
      proapoptotic functions of A20 in ECs and SMCs respectively qualify the positive
      effect of A20 upon vascular remodeling and healing. We propose that A20-based
      therapies may be effective in prevention and treatment of TV.

PMID- 17175231
TI  - Early short-term platelet-derived growth factor inhibition prevents the
      development of chronic allograft nephropathy in experimental rat kidney
      transplantation.
AB  - Chronic allograft nephropathy (CAN) remains the primary reason for late allograft
      loss in kidney transplantation. Platelet-derived growth factor (PDGF) is a major
      mitogen mediating mesenchymal cell proliferation in CAN. When administered
      continuously the PDGF receptor tyrosine kinase inhibitor imatinib prevents the
      development of CAN and restores kidney function in experimental kidney
      transplantation. Herein we investigated whether early short-term imatinib
      treatment prevented CAN. Kidney transplantations were performed from DA to WF
      rats and syngenic controls were done between DA rats. Allograft recipients were
      immunosuppressed with cyclosporine (CsA; 1.5 mg/kg/d sc). One group of allografts
      was also treated with imatinib (10 mg/kg/d po). Serum creatinine levels were
      measured once a week. Grafts were harvested 90 days after transplantation for
      histology and immunohistochemistry (PDGF-AA, -BB, PDGFR-alpha, -beta).
      Histological changes were scored according to the Chronic Allograft Damage Index
      (CADI). Among syngenic grafts, no signs of CAN were observed, namely, CADI 0.3 +/
      0.2 (mean +/- SEM). Control allografts showed moderate to intense chronic
      changes, CADI 6.5 +/- 1.3. Early short-term imatinib treatment significantly
      prevented the development of CAN compared with control allografts. Only a few
      histological changes were seen, namely, CADI 3.3 +/- 1.4. Compared with control
      allografts PDGF ligand and receptor induction was significantly inhibited by
      imatinib to nearly the same level as in syngenic grafts. Creatinine values of
      imatinib-treated allografts were also lower than control allografts. Our results
      demonstrated that early short-term imatinib treatment significantly prevented
      CAN. This indicated that early PDGF induction has an important role in the
      pathogenesis of CAN.

PMID- 17175232
TI  - FoxP3+ T cells can be expanded from rejecting cardiac allografts.
AB  - A specific subset of T cells, the FoxP3+ regulatory T cells, control effector T
      cell responses to self and foreign antigens. In transplant patients, we and
      others have shown that high intragraft FOXP3 mRNA levels are associated with
      acute rejection, suggesting that immune regulation is dependent on immune
      activation. To study whether transplanted grafts harbor FoxP3+ T cells and to
      functionally analyze them, graft infiltrating lymphocytes (GILs) must be
      propagated from the transplanted tissue. In the present study, we analyzed
      whether FoxP3+ T cells can be grown from endomyocardial biopsies (EMBs; n = 5)
      from patients after heart transplantation during acute cellular rejection. After
      18 to 21 days of culture, 0.5 to 1.0 x 10(6) GILs were cultured from the EMBs. Of
      these GILs, 10.6% (median; range, 1.6%-17.1%) stained positive for FoxP3. Thus
      Foxp3+ T cells can be grown from EMBs, providing the tools to functionally
      characterize these cells in depth in forthcoming studies.

PMID- 17175233
TI  - Vascular endothelial growth factor (VEGF) ligand and receptor induction in rat
      renal allograft rejection.
AB  - BACKGROUND: Acute rejection is the single most important risk factor for the
      subsequent development of chronic allograft nephropathy (CAN), which is still the
      primary reason for late allograft loss in kidney transplantation. Vascular
      endothelial growth factor (VEGF) is a proangiogenic factor that has an important
      role in the development and maintenance of physiological endothelium. While its
      role has been characterized in the pathology of diabetic nephropathy and
      preeclampsia, its role in the development of acute and chronic allograft
      rejection remains unclear. METHODS: Kidney transplantations were performed from
      DA to WF rats and syngeneic control transplantations were performed between DA
      rats. Normal kidneys were used as controls to evaluate physiological VEGF and
      VEGFR-1 expression. Allografted rats were immunosuppressed with cyclosporine
      (CsA) (1.5 mg/kg/d subcutaneously); and no immunosuppression was given to
      syngeneic grafts. Grafts were harvested at 5 and 90 days after transplantation
      for histology and immunohistochemistry (VEGF, VEGFR-1). RESULTS: In normal
      kidneys VEGF ligand and receptor expression was almost nonexistent. Only mild
      glomerular, arterial, and tubular VEGF expression was seen. In syngeneic grafts,
      no histological signs of acute or chronic rejection were seen, whereas
      characteristics of both acute and chronic rejection were seen in CsA-treated
      allografts. Altough VEGF expression was increased in syngenic grafts when
      compared to controls it still remained mild in both the early and the late
      posttransplant period. In CsA-treated allografts moderate VEGF expression was
      seen already 5 days after transplantation; the expression increased at 90 days
      after transplantation. The same pattern was also discovered for VEGFR-1
      expression although the difference was not as remarkable after 5 days.
      CONCLUSIONS: Our results demonstrated that VEGF ligand and receptor expression
      was increased in both acute and chronic rejection. Our data suggested that VEGF
      may have an important role in the pathology of chronic rejection. Based on our
      findings VEGF inhibition could be a potential intervention to prevent CAN in
      clinical kidney transplantation.

PMID- 17175234
TI  - The effect of leflunomide analogue FK778 on development of chronic rat renal
      allograft rejection and transforming growth factor-BETA expression.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) remains the primary reason for
      late allograft loss in kidney transplantation. Transforming growth factor beta
      (TGF-beta) is a major mitogen mediating mesenchymal cell proliferation and
      epithelial to mesenchymal cell transition in CAN. FK778, an analogue of an active
      metabolite of leflunomide, is a promising immunosuppressive drug that inhibits de
      novo pyrimidine biosynthesis. Herein we investigated the effect of FK778 on
      development of chronic rejection and TGF-beta expression in combination with
      calcineurin inhibitors cyclosporine (CsA) and tacrolimus (Tac). METHODS: Kidney
      transplantations were performed from DA to WF rats and syngeneic control
      transplantations between DA rats. Allografts were immunosupressed alone with CsA
      (1.5 mg/kg/d subcutaneously) or Tac (1.5 mg/kg/d orally) or with combinations of
      FK778 (10 mg/kg/d orally) and CsA or Tac. No immunosuppression was given to
      syngeneic grafts. Grafts were harvested 90 days after transplantation for
      histology and immunohistochemistry (TGF-beta, TGF-betaR1). The chronic changes in
      allografts were scored according to the Chronic Allograft Damage Index (CADI).
      RESULTS: No histological signs of chronic rejection were seen in syngeneic
      grafts. According to CADI, moderate chronic changes were seen in grafts treated
      only with CsA or Tac. In both groups the changes typically associated with CAN
      were significantly ameliorated with FK778. CsA-treated grafts showed intense
      posttransplant expression of TGF-beta and TGF-betaR1 after 90 days. In grafts
      treated with Tac monotherapy this expression was substantially lower. FK778
      markedly reduced the expression of TGF-beta and TGF-betaR1 when combined with
      calcineurin inhibitors and lesser expression was demonstrated with the
      combination of FK778 and Tac. CONCLUSIONS: Our results demonstrated that FK778 is
      a potent immunosuppressive drug having synergistic effects with calcineurin
      inhibitors. When combined with CsA or Tac, it decreased posttransplant TGF-beta
      ligand and receptor expression. Our data also showed that FK778 prevented chronic
      changes typically associated with CAN. Taken together our results suggested that
      FK778 could be a promising therapy for CAN in clinical kidney transplantation.

PMID- 17175235
TI  - Cytotoxic T-cell response following mouse liver transplantation is independent of
      the initial site of T-cell priming.
AB  - BACKGROUND: Liver transplantation in the mouse results in systemic induction of
      tolerance. The underlying mechanisms may also account for the persistence of
      chronic liver infections. It has therefore been hypothesized that antigen (Ag)
      presentation within the liver by nonprofessional antigen-presenting cells (APC)
      leads to incomplete T-cell activation, ultimately resulting in tolerance
      induction. We tested this hypothesis in an orthotopic mouse liver transplantation
      model. METHODS: Mouse liver transplantation was used to manipulate antigen
      presentation in major histocompatibility complex (MHC)-disparate donor and
      recipient strains. The effect of restricted Ag presentation was studied using
      CD8+ T-cell receptor transgenic OT-I cells. Transgenic OT-I cells were activated
      by injection of their cognate peptide antigen SIINFEKL, which could be presented
      by the MHC class I of only one of the mouse strains. Depending on the strain
      combination, Ag presentation was restricted to either the transplanted liver
      itself, the recipient (excluding the transplanted liver), or systemically
      throughout the recipient. Extrahepatic Ag presentation by passenger leukocytes
      was eliminated by using donors of chimeric bone marrow. RESULTS: OT-I cells
      encountering antigen only in the transplanted liver were activated, underwent
      extensive proliferation, and developed effector functions, based on IFN-gamma
      production and in vivo cytotoxicity assays. This T-cell activation and
      differentiation within the liver was comparable to animals with systemic Ag
      presentation and to animals with absent hepatic-parenchymal Ag presentation.
      CONCLUSIONS: The restricted presentation of antigen in the liver showed no
      immunosuppressive effect on activation of CD8+ T cells. In contrast, the liver
      may be an excellent priming site for naive CD8+ T cells.

PMID- 17175236
TI  - Combination of donor-specific blood transfusion with anti-CD28 antibody
      synergizes to prolong graft survival in rat liver transplantation.
AB  - Donor-specific blood transfusion (DST) has been shown to effectively induce
      tolerance to certain allografts. In addition, it is well known that blockade of
      costimulatory signals reduces the ability of T cells to respond to alloantigens,
      prolonging allograft survival in some transplant models. We assessed the effects
      of single or multiple DSTs in the absence or presence of anti-CD28 monoclonal
      antibodies (mAbs) on graft function and host survival in rat liver
      transplantation (LTx). Fully MHC-mismatched adult male Dark Agouti (DA) and Lewis
      (LEW) rats were used as donors and recipients, respectively. Heparinized DA blood
      was administered to naive LEW rats 7 days before LTx [DST(-7d)], 14 and 7 days
      before LTx [DST(1 x 2)], twice a week for 2 weeks prior to LTx [DST(2 x 2)] and
      once a week for 4 weeks prior to LTx [DST(1 x 4)]. For some experiments, two
      different monoclonal antibodies (mAb) to rat CD28 (JJ316 and JJ319) were
      administered in combination with some DST treatments. We found that DST
      administration induced a time- and dose-dependent increase in host survival.
      Treatment of LEW rats with JJ316 or JJ319 mAb alone failed to prolong graft
      survival over untreated rats; however, the combination of DST(1 x 2) with JJ316
      or JJ319 mAb induced indefinite survival at 100 days following surgery. We found
      that this protective effect was associated with increased numbers of splenic CD4+
      CD45RC- but not CD4+ CD25+ foxp3+ T-cells in long-term survivors. Our data
      suggest that the combination of suboptimal DST with CD28 mAb induces donor
      specific tolerance that correlates with enhanced numbers of regulatory T-cells.

PMID- 17175237
TI  - Histone H1 vaccine therapy for overcoming acute rejection in experimental organ
      transplantation.
AB  - OBJECTIVE: In a rat tolerogenic orthotopic liver transplantation (OLT) model, the
      recipient serum (post-OLT serum) shows strong immunosuppressive activity. In our
      previous reports, we suggested that autoreactive antibody (Ab) against histone H1
      is a major immunosuppressive factor in this serum. The present study sought to
      determine whether up-regulation of anti-histone H1 Ab by histone H1 vaccination
      led to tolerance. MATERIALS AND METHODS: Using mixed lymphocyte reactions (MLR)
      and heterotopic heart transplantations (HHT), the alloreactive T-cell responses
      and allograft survivals of histone H1-immunized rats were compared with those of
      control rats. Cytokine and cellular profiles were determined by enzyme-linked
      immunosorbent assay (ELISA) and flow cytometry. RESULTS: The alloreactive T-cell
      response of histone H1-immunized rats was significantly lower than that of
      control rats, although there was no difference in nonspecific T-cell activation
      between the 2 groups. The allograft survival of histone H1-immunized rats was
      significantly prolonged after HHT. The major histocompatibility complex (MHC)
      class II and CD25 molecules of histone H1-immunized rats were significantly down
      regulated compared with those of control rats. Moreover, the serum cytokine
      profile was modified by the immunization with histone H1. CONCLUSIONS: These
      results suggest that histone H1 vaccination of transplant recipients leads to the
      production of immunosuppressive factors and the modification of cytokine/cellular
      profiles.

PMID- 17175238
TI  - Protective effect of portal vein arterialization in acute liver failure induced
      by hepatectomy in normal and fatty liver rat.
AB  - AIM: We sought to determine whether an additional supply of oxygenated blood
      achieved by partial portal vein arterialization (PPVA) was protective on normal
      or fatty liver (FL) in rats with acute liver failure (ALF) induced by
      hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated
      either to receive or not to undergo PPVA after hepatectomy. FL was induced by
      feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the
      left renal artery to the splenic vein with a stent following a left nephrectomy
      and splenectomy; the control rats underwent left nephrectomy and splenectomy
      only. Liver injury was evaluated by the serum alanine aminotransferase (ALT)
      level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect
      blood and liver tissue samples for biochemical analysis. The 7-day survival was
      assessed in separate experimental groups. RESULTS: PPVA significantly increased
      Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA
      significantly improved the 7-day survival compared with controls in both groups:
      hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%).
      Serum ALT levels were slightly lower in the PPVA groups compared with the non
      PPVA groups without a significant difference. Prothrombin activity decreased soon
      after hepatectomy in the normal and the FL liver groups but recovered rapidly
      thereafter without differences between the PPVA and non-PPVA treated animals.
      CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA
      promotes rapid resolution of ALF after partial hepatectomy in rats with normal or
      fatty livers, significantly improving 7-day survivals compared to hepatectomy
      controls.

PMID- 17175239
TI  - Immunological advantage on small bowel graft induced by simultaneously
      transplanted liver in porcine auxiliary liver/small bowel transplantation.
AB  - BACKGROUND: We developed a new porcine model for auxiliary liver/small bowel
      transplantation (LSBT). The possible immunological advantage on small bowel graft
      induced by simultaneously transplanted liver in the large animal was assessed.
      METHODS: Thirty outbreed long-white pigs were randomized into two groups. Group A
      animals received LSBT without immunosuppressive treatment (n = 10). Group B
      animals had segmental small bowel allotransplantation without immunosuppressive
      treatment (n = 10). The postoperative survival time, initial acute rejection
      time, and pathological rejection scores were analyzed. RESULTS: There was no
      remarkable difference in survival time between groups A and B (10.33 days vs
      12.89 days, P > .05), but the initial time of acute rejection in intestinal
      grafts in group A was obviously delayed when compared to group B (8.22 days vs
      4.33 days, P < .05), and the rejection scores in group A were remarkably lower
      than those of group B (0 vs 0.44 on postoperative day (POD) 3, P < .05; 0.22 vs
      1.78 on POD 5, P < .05; 1.11 vs 2.56 on POD 7, P < .05). CONCLUSIONS: An
      immunological advantage on intestinal graft can be induced by simultaneously
      transplanted liver in auxiliary LSBT. Compared to isolated segmental small bowel
      allotransplantation, the intestinal graft in LSBT has a delayed initial time of
      acute rejection and lower acute rejection scores. The liver graft may reduce the
      risk of intestinal rejection and thus protect the bowel graft.

PMID- 17175240
TI  - Thymectomy does not abrogate long-term acceptance of MHC class I-disparate lung
      allografts in miniature Swine.
AB  - We have previously reported that tolerance to class I disparate lung allografts
      in miniature swine could be induced using an intensive 12-day course of
      tacrolimus and that pretransplant sensitization with immunogenic MHC class I
      allopeptides failed to block the induction of tolerance. We also have previously
      reported the importance of the presence of the thymus in the induction of
      tolerance to isolated heart, kidney, and combined heart-kidney transplants. In
      this study, we examined the impact of thymectomy on tolerance induction in lung
      transplantation. METHODS: Orthotopic left lung transplantation was performed
      using MHC class I-disparate donors. The recipients received a 12-day course of
      high-dose tacrolimus (n = 6). Total thymectomies were performed in three of the
      swine 21 days prior to transplantation. Lung grafts were monitored by chest
      radiography and serial open lung biopsy. RESULTS: All euthymic recipients
      maintained their grafts for over 1 year. None of the thymectomized recipients has
      experienced graft loss in the 6 to 10 months following transplantation. Although
      isolated lesions of obliterative bronchiolitis were occasionally seen in one
      thymectomized animal on biopsy, donor-specific unresponsiveness has been observed
      on assays of cell-mediated lymphocytotoxicity in all recipients. Moreover, co
      culture assays have shown that recipient lymphocytes can strongly inhibit the
      normally robust response of naive recipient-matched lymphocytes to donor antigen.
      This inhibition was not seen when using stimulators primed with third-party
      antigens against appropriate targets. CONCLUSIONS: These data suggest that thymus
      independent peripheral regulatory mechanisms may be sufficient to induce and
      maintain long-term acceptance of the lung allografts.

PMID- 17175241
TI  - The role of indirect recognition of MHC class I and II allopeptides in a fully
      mismatched miniature swine model of lung transplantation.
AB  - Considerable evidence suggests that indirect recognition of MHC allopeptides
      plays an important role in solid-organ rejection. Here, we examine whether
      immunization with class I or class II allopeptides accelerates rejection in a
      fully MHC-mismatched lung transplant model in miniature swine. METHODS:
      Recipients were immunized with either donor-derived class I or class II peptides.
      Sensitization to the peptides was confirmed by DTH testing and in vitro
      proliferation assays. Nonimmunized control (n = 6), class I peptide-immunized (n
      = 3), and class II peptide-immunized (n = 3) swine were transplanted with fully
      mismatched lungs using only a 12-day course of tacrolimus. RESULTS: One control
      animal rejected its graft on postoperative day 103, while the others maintained
      their grafts for over 1 year. In the class I peptide-immunized group, two
      recipients rejected their grafts (days 14 and 52). The third animal has not
      rejected the graft (day 120, experiment is ongoing). In contrast, in the class II
      peptide immunized group, only one animal rejected its graft on day 52, while the
      others maintained their grafts over 1 year. Both anti-donor IgM and IgG
      antibodies were detectable in all acute rejectors, although no alloantibody was
      detectable in long-term acceptors. Regardless of the fate of the graft, all
      animals have maintained their proliferative responses to the peptides. However,
      only acceptors maintained donor-specific hyporesponsiveness in cell-mediated
      lymphocytotoxity and mixed lymphocyte reaction assays. CONCLUSIONS: Pretransplant
      sensitization of lung allograft recipients to donor allopeptides accelerates
      graft rejection. This appears particularly true for class I-derived allopeptides,
      suggesting that class II molecules may be less antigenic when presented
      indirectly.

PMID- 17175242
TI  - Cytoprotective gene HO-1 and chronic rejection in heart transplantation.
AB  - Chronic rejection in transplanted hearts or cardiac allograft vasculopathy (CAV)
      is the leading cause of late death among heart transplant recipients. We
      hypothesized that induction of HO-1 by D4-F, an apoA-I mimetic peptide with
      potent antiinflammatory/antioxidant properties, attenuated CAV. We utilized a
      previously characterized murine model of CAV. B6.C-H2(bml2) hearts were
      heterotopically transplanted into C57BL/6 mice. In the control group, recipient
      mice were treated with 20 microg of saline daily. In experimental group I, mice
      were treated daily with 20 microg of D4-F. In experimental group II, mice were
      treated daily with 20 microg of D4-F daily, plus CuPP, which does not have any
      effect on HO-1 activity. In experimental group III, recipient mice were treated
      with 20 mug of D4-F daily, plus SnPP, which is a competitive inhibitor of HO-1.
      Donor hearts were harvested on day 24 after transplantation. The donor hearts in
      the control group developed severe intimal lesions. In experimental group I,
      treatment with D4-F was associated with upregulation of HO-1 and a marked
      reduction in intimal lesions, which was consistent in experimental group II. In
      experimental group III, inhibition of HO-1 was associated with partial
      restoration of intimal lesions. Induction of HO-1 by an apoA-1 mimetic peptide
      was effective to control CAV. This class of antiinflammatory peptides, which show
      an ability to induce HO-1, provides a novel strategy for the treatment of CAV.

PMID- 17175243
TI  - Prolonged cardiac allograft survival in presensitized rats after a high activity
      Yunnan-cobra venom factor therapy.
AB  - Complement-dependent antibody-mediated acute humoral rejection is the major
      obstacle of clinical transplantation across ABO incompatibility and human
      leukocyte antigen presensitization. We previously demonstrated that Yunnan-cobra
      venom factor (Y-CVF) could almost completely abrogate complement activity and
      successfully prevent hyperacute rejection in some xenotransplant models without
      any obvious toxicity. In this study we investigated whether depletion of
      complement by Y-CVF prevented acute humoral allograft rejection in presensitized
      rats thereby prolonging graft survival. METHODS: Presensitization was achieved in
      Lewis rats by sequential grafting of three full-thickness skin pieces from Brown
      Norway rats. Serum cytotoxic alloantibody titers were determined by a modified in
      vitro complement-dependent microcytotoxicity assay. After presensitization, each
      Lewis rat received a heterotopic Brown Norway cardiac allograft. Fifteen
      recipients were divided into two groups: (1) no treatment control (n = 7); (2) Y
      CVF therapy group (86 u/kg, IV, day -1) (n = 8). After cessation of the heart
      beat, allograft rejection was confirmed by pathologic as well as IgG and C3
      immunohistochemical examinations. RESULTS: The mean graft survival time was
      significantly prolonged to 99.50 +/- 38.72 hours among rats that received Y-CVF
      vs 12.71 +/- 13.94 hours in nontreated controls (P < .001). Upon pathological and
      immunohistochemical examination, acute humoral rejection was mainly exhibited in
      the control group, whereas acute cellular rejection was mainly displayed in the Y
      CVF therapy group. CONCLUSIONS: Our study demonstrated that complement depletion
      by Y-CVF significantly inhibited acute humoral allograft rejection in
      presensitized rats. As a therapeutic immunointervention tool for complement, Y
      CVF has shown potential efficacy across ABO incompatible and positive cross-match
      barriers.

PMID- 17175244
TI  - Vascular endothelial growth factor plays a major role in development of
      experimental obliterative bronchiolitis.
AB  - Obliterative bronchiolitis (OB) is the major limitation for long-term survival of
      lung allograft recipients. The exact molecular and cellular mechanisms
      contributing to obliterative lesion formation are unknown. Pathological
      characteristics of OB are epithelial damage, peribronchial inflammation, and
      increasing obliteration of bronchioli. Vascular endothelial growth factor (VEGF)
      is an angiogenic growth factor that exerts proinflammatory effects by increasing
      endothelial permeability and inducing expression of endothelial adhesion
      molecules. We investigated the role of VEGF in the development of OB in rat
      tracheal allografts and the role of VEGF receptors (VEGFR)-1 and -2 in the
      development of OB in mouse tracheal allografts. In nontreated allografts, with
      increasing loss of epithelium and airway occlusion, VEGF messenger RNA (mRNA) and
      protein expression vanished in the epithelium and increased in smooth muscle
      cells and mononuclear inflammatory cells compared with syngeneic grafts.
      Intragraft VEGF overexpression by adenoviral transfer of a mouse VEGF164 gene led
      to a decrease in epithelial necrosis but increased luminal occlusion by >50%
      compared with AdLacZ-treated rat tracheal allografts. When compared with the
      control immunoglobulin (Ig)G group, simultaneous treatment with antibodies
      against VEGFR-1 and -2 significantly lowered the degree of luminal occlusion of
      mouse tracheal allografts.

PMID- 17175245
TI  - An MHC class II disparity raises the threshold for tolerance induction in
      pulmonary allografts in miniature swine.
AB  - OBJECTIVES: The mechanisms and treatment of chronic rejection in pulmonary
      allotransplantation remain elusive. We have induced robust tolerance to class I
      disparate lung allografts in miniature swine using an intensive 12-day course of
      tacrolimus. Here, we tested whether a tolerant state can be induced in swine
      receiving fully mismatched lung allografts. METHODS: Orthotopic left lung
      allografts were performed using MHC class I-disparate (group 1: n = 3) or fully
      disparate (group 2: n = 6) donors. The recipients received a 12-day postoperative
      course of tacrolimus (continuous intravenous infusion; target level = 35-50
      ng/mL) as their only immunosuppression. RESULTS: All swine in group 1 maintained
      their grafts long term without developing any lesions of chronic rejection (>497,
      >432, >451 days). These recipients exhibited donor-specific hyporesponsiveness in
      cell-mediated lymphocytotoxity (CML) and mixed lymphocyte reaction (MLR) assays.
      In group 2, five of the six recipients maintained their grafts long term
      (sacrificed on postoperative days 515, 389, 429, 481, and 438 with viable
      grafts). Isolated lesions of obliterative bronchiolitis were occasionally seen on
      biopsy, and donor-specific hyporesponsiveness on assays was consistently
      observed. The remaining recipient rejected its graft on day 103 with histologic
      findings of obliterative bronchiolitis. CONCLUSIONS: We report long-term graft
      acceptance without chronic immunosuppression in five of six recipients across a
      full MHC disparity, albeit with some evidence of obliterative bronchiolitis.
      These data suggest that the class II disparity inherent in a fully mismatched
      transplant increases the requirement for tolerance induction.

PMID- 17175246
TI  - The effect of platelet-derived growth factor ligands in rat cardiac allograft
      vasculopathy and fibrosis.
AB  - BACKGROUND: In chronic rejection, parenchymal fibrosis and cardiac allograft
      vasculopathy (CAV) characterized by neointimal growth are the leading causes of
      graft loss for heart transplant recipients. During alloimmune responses a variety
      of cytokines, adhesion proteins, and growth factors, such as platelet-derived
      growth factor (PDGF), are up-regulated. The PDGF family (AA, AB, BB, CC, DD),
      which acts mainly on connective tissue cells, is considered to be a potent
      mitogenic and chemotactic factor for fibroblasts and vascular smooth muscle
      cells. In this study, we evaluated the effects of PDGF ligands in chronic
      rejection. METHODS: Heterotopic heart transplantations were performed between
      fully major histocompatability complex-mismatched Dark Agouti to Wistar Furth
      rats receiving cyclosporine immunosuppression. Allograft coronary arteries were
      perfused with a recombinant adeno-associated virus (AAV) encoding enhanced green
      fluorescence protein (EGFP) as a control gene or PDGF-A, -B, -C, -D. Allografts
      were harvested at 100 days for morphometric analysis of CAV and fibrosis.
      RESULTS: AAV-mediated transgene expression was detected by EGFP immunoreactivity
      across the graft section (at 100 days) in AAV EGFP-perfused allografts. AAV PDGF
      A, -C, and -D perfusion resulted in accelerated CAV and fibrosis. In contrast,
      AAV PDGF-B perfusion did not induce arteriosclerotic changes or fibrosis in
      cardiac allografts. CONCLUSIONS: AAV PDGF-A, -C, and -D overexpression
      accelerated the development of chronic rejection, whereas PDGF-B did not. Our
      results suggested that more targeted therapy with monoclonal antibodies blocking
      the active sites of PDGF-A, -C, and -D may produce beneficial effects on heart
      transplant survival.

PMID- 17175248
TI  - Mycophenolic acid induces islet apoptosis by regulating mitogen-activated protein
      kinase activation.
AB  - Mycophenolic acid (MPA), an inosine monophosphate dehydrogenase inhibitor, is
      widely used as an immunosuppressive drug after transplantations including those
      of pancreas islet cells. However, recent reports have indicated that MPA has
      apoptotic effects on islet cells in vitro. To study the effect of MPA on islet
      cells and determine its mechanism, we used an insulin secreting cell-line, HIT
      T15. We examined mitogen-activated protein kinase (MAPK) activation after MPA
      treatment, and determining cell death levels using methylthiazdetetrazolium
      assays. The activations of extracellular signal-regulated protein kinase (ERK), c
      jun N-terminal kinase (JNK), and p38 MAPK and caspase-3 cleavage were measured by
      Western blotting. MPA (1, 10, 30 micromol/L) increased cell death and caspase-3
      cleavage within 24 hours. Exogenous 500 micromol/L guanosine reversed the MPA
      induced islet cell death, but exogenous adenosine did not. MPA 10 micromol/L
      induced cell apoptosis and increased the activations of JNK, ERK, and p38 MAPK.
      Furthermore, exogenous guanosine, but not exogenous adenosine, reversed these
      effects induced by MPA. This study demonstrated that MPA may induce islet
      apoptosis in HIT-T15 cells by increasing activations of JNK, ERK, and p38 MAPK in
      a guanosine-dependent manner.

PMID- 17175249
TI  - Organogenesis of pancreatic anlagen allografted in rats.
AB  - AIMS: To study the possibility of revascularization, growth, and differentiation
      of embryonic pancreatic anlagen transplanted to adult hosts. While
      transplantations of pancreas and islets are the main methods to cure diabetes
      mellitus, the donor source is in shortage. So it's necessary to find a new source
      for transplantation. METHODS: The pancreas from embryonic day 14.5 (E14.5) and
      15.5 (E15.5) Lewis rat embryos were implanted into either intraperitoneal or
      subrenal capsular site of healthy Lewis rats. at 3 weeks or 6 weeks after
      implantation, the pancreatic anlagen in the host rats were resected for size
      measurements, as well as histopathologic and immunohistochemical examinations.
      RESULTS: Three weeks after implantation into the renal-capsular site, the size of
      both E14.5 and E15.5 pancreatic anlagen had enlarged 10- to 15-fold with
      differentiation of acinar components upon histological examination. Moreover,
      increasing numbers of beta cells and islets stained positive for insulin, and
      newly generated vessels were observed around the tissues. Continued proliferation
      of the endocrine islets in E14.5 pancreatic anlagen grafts was observed after
      another 3 weeks, whereas further proliferation in the E15.5 pancreatic anlagen
      graft was not seen. Additionally fibrosis appeared in the exocrine component of
      both E14.5 and E15.5 pancreatic anlagen at this time point. When implanted into
      intraperitoneal site, enlarged E15.5 pancreatic anlagen with proliferatels beta
      cells were also observed after 3 weeks. However, both the size of the pancreatic
      anlagen and the proliferation of the beta cells were much less than that in the
      subrenal capsular site. CONCLUSIONS: The allografted E14.5 and E15.5 pancreatic
      anlagen revascularised and grew into tissues that were structurally similar to
      normal mature rats pancreatic tissue. Adequate embryonic age for the
      transplantation of pancreatic anlagen is 14.5 and 15.5 days old. Subrenal capsula
      is a more suitable site than the peritoneal cavity for implantation of pancreatic
      anlagen.

PMID- 17175247
TI  - Continuous glucose monitoring system for early detection of graft dysfunction in
      allogenic islet transplant recipients.
AB  - BACKGROUND: There are no effective indicators of graft dysfunction in islet
      transplantation. This study evaluated the role of the Continuous Glucose
      Monitoring System (CGMS) as an early indicator of graft dysfunction in islet
      transplant recipients. METHODS: In 5 islet allograft recipients, we
      retrospectively determined the date of graft dysfunction: 3 fasting blood glucose
      levels >7.8 mmol/L (140 mg/dL) and/or 3 postprandial blood glucose levels >10
      mmol/L (180 mg/dL) in 1 week. We then determined 2 time points in respect to
      graft dysfunction, 5 to 9 months before (time point A) and 2 to 3 months before
      (time point B). For these 2 time points, we assessed the following: HbA1c, C
      peptide (CP), C-peptide glucose ratio (CPGR), 90-minute glucose from mixed meal
      tolerance test, and percentage of capillary blood glucose levels >7.8 mmol/L
      (%CBG >7.8) in a 15-day interval (1 week before and after CGMS placement). From
      the CGMS recordings, we calculated the glucose variability and the percentage of
      time spent in hyperglycemia >7.8 mmol/L (%HGT >7.8) and >10 mmol/L (%HGT >10).
      RESULTS: No difference was found between time points A and B for the following
      parameters: HbA1c, CP, CPGR, 90-minute glucose, %CBG >7.8, and %HGT >10. We
      observed a statistically significant increase from time point A to time point B
      in glucose variability (1.1 +/- 0.5 mmol/L to 1.6 +/- 0.6 mmol/L; P = .004), and
      in the %HGT >7.8 (11 +/- 12% to 22 +/- 18%; P = .036). CONCLUSION: Glucose
      variability and %HGT >7.8 determined using CGMS are useful as early indicators of
      graft dysfunction in islet transplant recipients. Further studies with larger
      sample sizes will help validate these observations.

PMID- 17175250
TI  - Enhancing engraftment of neonatal porcine xenoislet with CTLA4Ig and
      nordihydroguaiaretic acid.
AB  - This study examined the combinatory effect on graft survival of neonatal pig
      pancreatic cell clusters (NPCC) with nordihydroguaiaretic acid (NDGA), a 5
      lipoxygenase inhibitor, with systemic CTLA4Ig expression, with local CTLA4Ig and
      with interleukin-1 (IL-1) receptor antagonist (IL-1ra) expression using a pig to
      mouse model. About 2000 NPCCs, which were infected with both adenoviruses
      carrying CTLA4Ig and IL1-1ra genes (each 500 pfu/NPCC), were transplanted beneath
      the kidney capsule of diabetic BALB/c mice. Two days before transplantation, the
      recipient mice were either injected with (group C, n = 4; group D, n = 6) or
      without (group A, n = 7; group B, n = 9) 1 x 10(13) pfu/kg body weight of
      adenovirus carrying the CTLA4Ig gene. Mice in groups B and D received daily
      injections of NDGA (20 mg/kg body weight) subcutaneously for 4 weeks. Blood
      glucose levels less than 200 mg/dL were defined to be normoglycemic and the
      transplant termed as a functioning graft for the purpose of calculating mean
      graft function time (MFT). Four weeks posttransplantation, an intraperitoneal
      glucose tolerance test (IPGTT) was performed to calculate the area under the
      curve (AUC). Blood glucose levels in groups C and D were significantly lower than
      groups A and B at 1, 2, and 3 weeks after transplantation. Graft MFT and AUC of
      IPGTT in group D were significantly different from those in groups A and B. Our
      data suggested that a high dosage of systemic expression of CTLA4Ig was effective
      to enhance xenograft survival and that in it was reinforced by a combination with
      the macrophage inhibitor NDGA.

PMID- 17175251
TI  - Adenoviral-mediated overexpression of membrane-bound human FasL and human decoy
      Fas protect pig islets against human CD8+ CTL-mediated cytotoxicity.
AB  - Pig islets are considered to be most suitable source of islets for
      xenotransplantation into patients with type 1 diabetes mellitus. However,
      cellular rejection, especially CD8+ CTL-mediated cytotoxicity, remains a
      formidable barrier preventing long-term xenograft survival. Our previous study
      demonstrated that human CD8+ CTLs were highly detrimental to xenograft cells and
      that this strong cytotoxicity of human CTLs was mediated mainly by the Fas/FasL
      apoptotic pathway. Furthermore, we exploited novel methods for inhibiting human
      CD8+ CTL-mediated xenocytotoxicity with overexpression of membrane-bound human
      FasL and human decoy Fas antigen in xenografted cells. In the present study, we
      assessed the cytoprotective effects of these novel inhibitory molecules
      overexpressed by an adenoviral-mediated system in pig islets. Isolated pig islets
      were transfected with adenovirus vector encoding either human decoy Fas or
      membrane-bound human FasL genes. Thirty percent to 60% of transfected pig islets
      expressed these molecules producing 60% to 88% suppression of CTL killing
      compared with parental pig islets. These data indicated that pig islet grafts
      isolated from transgenic pigs with either membrane-bound human FasL or human
      decoy Fas antigen genes may control the innate cellular response to xenografts,
      and creating a window of opportunity to facilitate xenograft survival.

PMID- 17175252
TI  - Intraperitoneal injection of oxygenated perfluorochemical improves the outcome of
      intraportal islet transplantation in a rat model.
AB  - A 50% to 75% early graft loss upon engraftment has been suggested to in
      intraportal islet transplantation (IPIT). Hypoxia in the portal vein contributes
      to graft loss in immediately posttransplantation. Herein we examined the effect
      on the outcome of IPIT of intraperitoneal oxygenated perfluorochemical (PFC) as
      an oxygen carrier. Isolated Lewis rat islets were transplanted into the portal
      vein of a chemically induced diabetic syngeneic rat. First, 1500 IEQ was
      determined to be the optimal dose in this study. When oxygenated PFC (group 1)
      was intraperitoneally injected following IPIT of 1500 IEQ, the success rate of
      transplantation was 5/6, in contrast to 1/6 when PFC with no oxygen was injected
      (group 2) and 1/6 in IPIT without PFC, respectively. The area under the glucose
      profile curve on intraperitoneal glucose tolerance tests on posttransplant day 28
      in group 1 was significantly smaller than that for group 2. In conclusion,
      intraperitoneal oxygenated PFC improved the outcome of IPIT.

PMID- 17175253
TI  - Tissue engineering of endothelial cells and the immune response.
AB  - BACKGROUND: While tissue engineering offers promise for organ and tissue
      transplantation, it can also be used to examine transplant and immune biology.
      Endothelial cells engrafted within 3-dimensional matrices create stable units
      that produce all of the factors of a functional quiescent endothelium.
      Perivascular implantation of tissue engineered endothelial cell constructs
      provides long-term control of vascular repair after injury. This control is
      established without restoration of the natural luminal:mural endothelium, and
      most intriguingly, without engendering host allo- and xenogeneic immune
      responses. We examined how endothelial immunogenicity is controlled by
      interaction with 3-dimensional matrices. MATERIALS AND METHODS: Human aortic
      endothelial cells (HAE) were either grown to confluence on polystyrene tissue
      culture plates or within 3-dimensional collagen-based matrices. Major
      histocompatibility complex (MHC) class II, integrin, interferon (IFN)-gamma
      receptor expression, and signaling were analyzed via confocal microscopy, flow
      cytometry, reverse transcription polymerase chain reaction (RT-PCR), and
      microarray. Splenocyte proliferation was assayed by thymidine incorporation.
      RESULTS: Despite similar expression levels of IFN-gamma receptors, matrix
      embedded HAE elicited far less STAT-1 phosphorylation upon IFN-gamma stimulation,
      and expressed 2-fold less MHC II than HAE grown to confluence on culture plates
      (P < .001). This effect correlated with reduced expression of integrin alpha(v)
      and beta(3) (P < .002), and muted proliferation of porcine splenocytes (P <
      .001). CONCLUSIONS: Matrix architecture is critical for modulation of endothelial
      immunogenicity. Embedding HAE within a physiologic 3-dimensional environment
      affects activity of intracellular signaling pathways, MHC II expression, and
      subsequent activation of immune cells. These findings might offer novel insights
      into our understanding of endothelial-mediated diseases and might enhance our
      ability to leverage the potential for cell-based therapies.

PMID- 17175254
TI  - A pathological analysis of lymphatic vessels in early renal allograft.
AB  - Lymphatic vessels are an essential part of the immunological response.
      Nevertheless, little is known about the pathology of renal transplant rejection.
      In part the reason may be not distinguishing peritubular capillaries from
      lymphatic vessels by periodic acid-Schiff (PAS) staining. This study examined the
      morphology of lymphatic vessels in early renal allografts using double staining
      with PAS and podoplanin. The 41 cases were divided into four categories: (I)
      acute antibody-mediated rejection, (II) acute cellular rejection, (III)
      peritubular capillaritis only, and (IV) controls. I through III had the evidence
      of peritubular capillaritis exceeding grade 1 on a biopsy obtained an average of
      17.3 +/- 5.5 days after kidney transplantation. In addition, each lymphatic
      vessel density (LVD) and nodular lesion of lymphocytes (NL) were quantified as
      the number of each podoplanin-positive vascular profiles and NL per unit area of
      cortex measured Lumina Vision (Mitani). The average of the LVD was 73.0, 35.1,
      37.1, and 8.1 per 10 mm2 for groups I to IV and the average of NL was 2.8, 5.5,
      1.3, 0.9, respectively. There was a significant correlation between LVD and NL.
      NL showed a strong relation to the accumulation of lymphocytes in lymphatic
      vessels (AL); 22% of the AL scores were greater than the peritubular capillaritis
      grade. We found lymphatic vessels to be strongly associated with any kind of
      inflammatory process that occurred unexpectedly soon after kidney
      transplantation. In addition, to avoid misdiagnosis of peritubular capillaritis,
      NL in early renal allograft must especially be excluded.

PMID- 17175255
TI  - Antisense ERK1/2 oligodeoxynucleotide gene therapy attenuates graft
      arteriosclerosis of aortic transplant in a rat model.
AB  - Chronic rejection is a major cause of transplant loss that is effected by the
      extracellular signal-regulated kinases (ERK) pathway. This study investigated the
      effects of antisense ERK1/2 oligodeoxynucleotide(ODN) gene therapy on chronic
      rejection. METHODS: Lewis (RT1(1)) rats served as recipients of Brown-Norway (BN,
      RT1n) grafts. The BN rat abdominal aortas were harvested and orthotopically
      grafted into Lewis rats. The recipients were divided into three groups: (1)
      control group (n = 9), (2) random ODN transfer group (n = 10), and (3) antisense
      ODN transfer group (n = 10). At day 60 after transplantation, the recipients were
      sacrificed; the grafted aortas were evaluated histologically and
      immunohistochemically. ERK1/2 protein expression in the grafts was determined
      using Western Blot assays. Serum levels of slCAM-1 were detected by ELISA.
      RESULTS: In the control group and random ODN transfer group, we observed a
      remarkable degree of intimal hyperplasia and inflammatory cell infiltration,
      including macrophages and T cells. Compared with the control group, antisense
      ERK1/2 ODN gene therapy resulted in a significant reduction in neointimal
      proliferation (P < .01), inhibition of ERK1/2 protein expression (P < .01),
      decreased graft infiltration with CD4+ T lymphocytes (P < .01), CD8+ T
      lymphocytes(P < .05), and ED-1 macrophages (P < .01) with decreased serum levels
      of sICAM-1 (P < .05). We obtained a negative correlation between ERK1/2
      expression and immune cell infiltration or ICAM-1 level. CONCLUSIONS: Antisense
      ERK1/2 gene therapy can attenuate graft arteriosclerosis so as to protect aortic
      allografts. The protection seemed to correlate with inhibition of inflammatory
      infiltration, implying that the ERK1/2 signal transduction pathway plays an
      important role in the process of chronic vascular rejection.

PMID- 17175256
TI  - Experimental study on genistein prevention and treatment of transplant
      arteriosclerosis in aortic transplants of rat.
AB  - OBJECTIVE: Our objective was to study the effects of genistein, a soy isoflavone,
      on transplant arteriosclerosis, in addition to its immunosuppressive and
      antioxidant properties. MATERIALS AND METHODS: We performed male Brown-Norway to
      male Lewis aortic transplantation. The recipients were randomly assigned to 3
      groups: no treatment controls, dimethyl sulfoxide (DMSO; 5 mL/kg) solvent
      controls, and experimental group that received genistein (20 mg/kg/d) by daily
      intraperitoneal injection. On postoperative day 60, the graft was harvested and
      blood obtained. The transplanted aorta was analyzed by histology and
      immunohistochemistry. The serum was analyzed by an enzyme-linked immunosorbent
      assay (ELISA). RESULTS: Compared with the 2 controls, leukocyte recruitment to
      the graft was significantly inhibited by genistein, with a profound reduction in
      the number of CD69 macrophages infiltrating the adventitia of the transplanted
      aortas. Moreover, genistein significantly inhibited the expression of VEGF and
      IFN-gamma production (P < .01). CONCLUSION: These results suggested that the
      protein tyrosine kinase inhibitor genistein inhibited graft arteriosclerosis.

PMID- 17175257
TI  - Sertoli cells induce xenolymphocyte apoptosis in vitro.
AB  - BACKGROUND: Testicular Sertoli cells can protect pancreatic islet grafts from
      allo- and autoimmune destruction; however, the mechanisms underlying immune
      privilege of the testicle are not well understood, especially in
      xenotransplantation. The purpose of this study was to investigate whether rat
      Sertoli cells could induce mouse lymphocyte apoptosis in vitro. METHODS: Testis
      was isolated from 2- to 4-week-old Sprague Dawley (SD) rats. Sertoli cells were
      successfully prepared by digestion with collagenase type V, trypsin, and DNase I,
      and then identified by electron microscope. Viability and apoptosis of cultured
      cells were measured by flow cytometry. We examined the apoptosis rates of Balb/c
      mouse lymphocytes, which were cocultured with SD rat Sertoli cells by FACS. The
      expression of Fas ligand (Fasl), transforming growth factor (TGF)-beta1 and
      clusterin on Sertoli cells were detected by immunocytochemistry. RESULTS: In the
      cocultured system, Sertoli cells accounted for more than 93%. With our isolation
      method, the viability of Sertoli cells was more than 95% and the apoptosis rate
      was 10.87% +/- 3.87%. The lymphocyte apoptosis ratio was 15.52 +/- 0.17 (P < .01,
      compared with the control groups). SABC immunochemistry staining showed that the
      sertoli cells could express FasL, TGF-beta, and clusterin. CONCLUSIONS: In our
      coculture in vitro, rat Sertoli cells expressed FasL and TGF-beta1 as well as
      induced the apoptosis of mouse lymphocytes. These results indicated that the
      expression of FasL and TGF-beta1 on Sertoli cells might relate to immune
      privilege in xenotransplantation.

PMID- 17175258
TI  - A study of soluble HLA-G1 protecting porcine endothelial cells against human
      natural killer cell-mediated cytotoxicity.
AB  - Human natural killer (NK) cells, which can mediate direct lysis of porcine
      endothelial cells, play an important role in xenograft rejection. HLA-G, which is
      a critical molecule in maintaining maternal immune tolerance of semi-allogenic
      fetus, is able to protect susceptible target cells from lysis induced by NK
      cells. In this study, we investigated whether soluble HLA-G1 (sHLA-G1) protected
      porcine xenogeneic cells against human NK cell-mediated lysis. METHODS: The human
      sHLA-G1 genomic DNA (pcDNA3-sHLA-G1) was transfected into a B lymphoblastoid cell
      line 721.221 (LCL721.221) by nucleofector. The sHLA-G1 expression of the
      transfected LCL721.221 cells was identified by RT-PCR and Dot-ELISA. The sHLA-G1
      protein was purified by affinity chromatography on anti-HLA-ImAb W6/32 coupled to
      cyanogen-bromide-activated Sepharose 4B from culture supernates of transfectants.
      Various concentrations of sHLA-G(1) protein (0, 2, 4, 6, or 8 microg/mL) were
      added to a NK cell-mediated xenogenic cell lysis system with either NK92 cells or
      fresh human peripheral blood mononuclear cells (PBMCs) cocultured with the
      porcine endothelial cells line. A LDH release assay was used to evaluate NK cell
      mediated cytotoxicity. RESULTS: sHLA-G1 provided significant protection of
      porcine endothelial cells against human NK-mediated cytotoxicity in a dose
      dependent manner. The rates of NK92 cell-mediated cytotoxicity were reduced to
      83.4 +/- 5.7% (2 microg/mL), 56.6 +/- 9.3% (4 microg/mL), 39.3 +/- 10.2% (6
      microg/mL), and 31.2 +/- 4.9% (8 microg/mL) versus 96.9 +/- 3.0% in the control
      group (P < .01). Similarly, adding 6 microg/mL sHLA-G1 reduced the mean rate of
      PBMC-mediated cytotoxicity (n = 4) to 5.8 +/- 1.6% from 23.9 +/- 1.3% in the
      control group (P < .01). CONCLUSIONS: These results indicated that sHLA-G1
      protected xenogeneic porcine endothelial cells against attack by human NK cells,
      thus providing a new approach to overcome NK-mediated immunity to xenografts.

PMID- 17175259
TI  - A novel strategy for preventing human CD8+ cytotoxic T lymphocyte-mediated
      cytotoxicity against pig endothelial cells by overexpression of pig cellular
      FLICE-like inhibitory protein (c-FLIP) gene.
AB  - Human CD8+ cytotoxic T lymphocyte (CTL)-mediated cytotoxicity in xenograft
      recipients is an important obstacle for successful xenotransplantation of pig
      organs into humans. In our previous study, we demonstrated that xenocytotoxicity
      of human CD8+ CTL detrimental to pig endothelial cells (PEC) is mediated mainly
      by the Fas/FasL apoptotic pathway. Furthermore, we developed new methods to
      prevent this CTL killing by extracellular remodeling using overexpression of
      human decoy Fas antigen and membrane-bound human FasL on pig xenograft cells. The
      cellular FLICE-inhibitory protein (c-FLIP), a caspase-8 inhibitor that lacks the
      cysteine domain, is a negative regulator of death receptor-mediated apoptosis. c
      FLIP proteins exist as long (c-FLIP(L)) and short (c-FLIPs) splice variants, both
      capable of protecting cells from death receptor-mediated apoptosis. In this
      report, we have demonstrated that both pig c-FLIPs and pig c-FLIP(L)
      significantly inhibit human CD8+ CTL-mediated xenocytotoxicity toward stably
      transfected PEC, although the expression level of pig Fas antigen on cell surface
      was not changed. These data suggested that intracellular remodeling with
      overexpression of pig c-FLIP in xenograft cells may decrease the innate cellular
      responses against xenografts, facilitating long-term xenograft survival.

PMID- 17175260
TI  - Altered expression of hepatocyte growth factor in cardiac allografts of nonhuman
      primates.
AB  - Hepatocyte growth factor (HGF) plays a critical role in transplant rejection.
      Herein we addressed whether HGF expression could be used for accurate and early
      diagnosis of acute and chronic rejection in cardiac transplantation. We used a
      heterotopic cardiac transplantation model using nonhuman primates (Macaca
      fuscata, n = 7). The grafts were harvested on days 1, 7, 22, 28, 40, 41, and 95
      for histology and immunohistochemistry. Histopathologically, HGF was expressed in
      the spindle-shaped cells of the acutely rejecting myocardium. The expression of
      HGF was enhanced in both thickened intima and media of the coronary arteries.
      Altered HGF expression is a sensitive indicator for acute and chronic cardiac
      rejection.

PMID- 17175261
TI  - Cross-species function of the pig C1 esterase inhibitor.
AB  - BACKGROUND: The use of a bioartificial liver with pig cells for the treatment of
      fulminant hepatic failure will require research on the plasma complement
      regulatory proteins of the pig, because the liver produces most of the complement
      components and plasma complement regulatory proteins. In our previous study, the
      pig C1 esterase inhibitor (C1-INH), which functions as an inhibitor of the
      complement reaction in the first step of the classical pathway in the fluid
      phase, was cloned and some relevant features of the molecule were characterized,
      especially its cross-species regulation, in comparison with human C1-INH. In a
      further analysis, the species specificity of C1-INH was examined, using pig
      endothelial cells (PEC) and several types of sera. MATERIALS AND METHODS: The
      cDNA of pig C1-INH was used to produce the membrane type pC1-INH, pC1-INH-PI, and
      inserted into the cloning site of pCXN2 (chicken beta actin promoter). The
      pCX/pCl-INH-PI plasmid was then transfected into PEC to establish stable PEC with
      pCl-INH-PI. The expression of the pCl-INH-PI was evaluated by a FACS analysis,
      and complement-dependent cell lysis with human, dog, rabbit, and mouse sera was
      then assessed. RESULTS: The transfectant with pig Cl-INH-PI showed a high level
      of expression on PEC. The PEC transfectants showed an inhibitory effect on
      complement-dependent PEC lysis. Pig Cl-INH did not show the same suppressive
      effect for each serum. However, considering the alternative pathway activation of
      each serum on the pig cell membrane, it can be concluded that pCl-INH has a
      relatively small species restriction. CONCLUSION: Pig Cl-INH, having a similar
      structure to human Cl-INH, shows a strong complement regulatory function on other
      species sera.

PMID- 17175262
TI  - Establishment of an animal model with side effects induced by mycophenolate
      mofetil and pharmacohistological analysis of them.
AB  - Mycophenolate mofetil (MMF) is used for immunosuppression after organ
      transplantation, but gastrointestinal side effects including diarrhea are
      sometimes observed with this drug. We sought to construct on animal model of
      diarrhea with MMF in rodents. MATERIALS AND METHODS: BALB/Cj mice, weighing 25 g
      received 500 mg /kg of MMF, 60 mg/kg of levofloxacin (LVFX), 1000 mg/kg of
      Hangeshashin-to (HST), which is traditional Kampo medicine. This cocktail was
      administered orally to MMF, LVFX, HST, MMF+LVFX, and MMF+LVFX+HST groups for 21
      days. We measured the water content fecal collected on days 1, 4, 8, 11, 14, 18,
      and 21. Feces on day 21 were cultured for identification of fecal flora. Mice
      were sacrificed on day 21, with blood samples collected to measure mycophenolic
      acid (MPA) concentrations by HPLC. Jejunum, cecum, and colon were taken for
      histological evaluation. RESULTS: Significant weight loss of mice and increased
      fecal water content of were observed in MMF and MMF+LVFX but not in MMF+LVFX+HST
      groups. Serum MPA levels didn't differ in MMF-administered groups. Inflammatory
      changes in intestinal villi were observed in the cecum in MMF and MMF+LVFX
      groups. A change in fecal flora was observed in LVFX-administered groups.
      CONCLUSION: Diarrhea induced by MMF in a rodent model produced inflammatory
      changes in the cecum. LVFX seemed to change the activity of beta-glucuronidase in
      the fecal flora. HST suppressed fecal softening induced by MMF in this animal
      model.

PMID- 17175263
TI  - Paradoxical response to tacrolimus assessed by interleukin-2 gene expression.
AB  - BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are potent
      immunosuppressive drugs, used mainly after organ transplantation. Methods to
      monitor their pharmacodynamic effects are not well established. METHODS: Whole
      blood samples from healthy volunteers (n = 16) were incubated for 24 hours in
      culture medium; each sample was preincubated for 2 hours with or without
      tacrolimus. An identical procedure was performed for 7 samples using blood from
      renal transplant patients before transplantation. Following the culture period,
      total RNA was isolated and quantitative reverse transcriptase polymerase chain
      reaction, using TaqMan probes, was employed to quantify interleukin-2 (IL-2) mRNA
      expression, and IL-2 mRNA copy number was reported by reference to a standard
      curve. RESULTS: IL-2 mRNA synthesis was suppressed by the presence of tacrolimus
      in most cases, compared with a control sample. However, some samples demonstrated
      up-regulation of mRNA expression. In the patient samples, there was up-regulation
      of IL-2 mRNA in two samples and, after transplantation, these patients developed
      acute rejection. CONCLUSION: Quantitative measurement of cytokine IL-2 regulated
      gene expression may represent a method to assess the efficacy of calcineurin
      inhibitor drugs.

PMID- 17175264
TI  - Changes in abdominal wounds following treatment with sirolimus and steroids in a
      rat model.
AB  - Wound healing complications have been observed in patients receiving sirolimus
      (SLR). This study examined the degree and duration of delayed healing in various
      protocols using SLR. Sprague-Dawley rats underwent a standard midline abdominal
      incision and wound closure. Groups of 6 rats each were randomized to receive
      different doses of SLR (2 and 5 mg/kg) with or without loading dose (10 mg/kg x3
      days), and with or without steroids (20 mg/kg x3 days followed by 5 mg/kg for 2
      weeks). Rats were humanely killed on postoperative days 5, 10, or 15. Wound
      breaking force was measured using the EHMI BIAX-II instrument and tensile
      strength was calculated. Wounds in control animals had gradual increase in
      tensile strength during the 15-day observation. In contrast, high and loading
      doses of SLR caused reduction in wound strength until day 10, but the wounds'
      tensile strength became equivalent to control by day 15. The addition of steroids
      prolonged wound recovery with low doses of SLR until day 15 and had very profound
      effects on healing in high-dose SLR-treated animals (>50% reduction) that
      continued beyond the 2 weeks of observation. Low doses of SLR in non-steroid
      treated animals had a short-term (5-day) impact on wound healing; high dose and
      loading doses delayed healing for 10 to 15 days. The addition of steroids had a
      synergistic effect on delayed wound healing, particularly in animals receiving
      high-dose SLR, which demonstrated prolonged wound weakness. These results may
      provide practical guidelines for postoperative introduction of SLR in the context
      of various clinical protocols.

PMID- 17175265
TI  - Genomic profiling of kidney ischemia-reperfusion reveals expression of specific
      alloimmunity-associated genes: Linking "immune" and "nonimmune" injury events.
AB  - Increased organ ischemia time leads to delayed graft function (DGF), increased
      acute rejection (AR), enhanced chronic allograft nephropathy (CAN), and reduced
      long-term allograft survival. The mechanisms by which IRI predisposes to AR and
      CAN are unknown. We hypothesized that gene expression profiling of ischemia
      reperfusion injury (IRI)-affected kidney would identify how IRI predisposes to AR
      and CAN. Furthermore, we examined how current immunosuppressive drug molecular
      targets are altered by IRI. C57BL/6J mice were exposed to 30 (n = 3) or 60 (n =
      3) minutes of bilateral kidney ischemia or sham surgery (n = 5). At 36 hour
      kidney tissue was collected and analyzed using Affymetrix 430MOEA (22626 genes)
      array and GC-RMA-SAM pipeline. Genes with the false discovery rate (q < 1%) and
      +/-50% fold change (FC) were considered affected by IRI. Genes coding for
      histocompatibility and antigen-presenting factors, calcineurin, and mammalian
      target of rapamycin (mTOR) pathway-associated proteins were selected using Gene
      Ontology (GO) analysis. GO analysis identified 10 and 17 alloimmunity-related
      genes affected by IRI induced by 30 and 60 minutes of ischemia, respectively,
      including Traf6 (FC = 2.99) and H2-D1 (FC = 2.58). We also detected significant
      IRI genomic responses in calcineurin and mTOR pathways represented by Fkbp5 (FC =
      4.18) and Fkbp1a (FC = 2.0), and Eif4ebp1 (FC = 16.8) and Akt1 (FC = 3.64),
      respectively. These data demonstrated that IRI up-regulates expression of several
      alloimmunity-associated genes, which can in turn enhance alloimune responses. Our
      discovery of IRI-induced up-regulation of genes associated with calcineurin and
      mTOR pathways are consistent with clinical observations that FK506 and Rapamycin
      can alter the course of DGF. Further validation and dissection of these pathways
      can lead to novel approaches by which improved management of early "nonimmune"
      transplant events can decrease susceptibility to more classic "immune" changes
      and CAN.

PMID- 17175266
TI  - Hyperbaric oxygenation attenuates renal ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Oxygen-derived free radicals play an important role in ischemia
      reperfusion injury (IR). Hyperbaric oxygenation (HO) decreases free radical
      production. The aim of this study was to determine the effect of HO treatment on
      renal ischemia-reperfusion injury in rats. METHODS: Rats were divided into four
      groups. All groups underwent right nephrectomy. Group I served as the control
      group; group II had left renal ischemia-reperfusion; group III was pretreated
      with HO; and group IV, ischemia-reperfusion and HO pretreatment. Tissue
      malondialdehyde (MDA) and glutathione (GSH) levels were measured, and
      histopathologic damage scored. RESULTS: HO pretreatment significantly decreased
      tissue MDA levels and histopathologic scores among rats with IR. There was an
      increased GSH in HO-pretreated rats with IR; however, the difference was not
      significant. CONCLUSION: HO prior to ischemia displayed a beneficial effect on
      renal IR by reducing oxygen radical peroxidation of lipid membranes.

PMID- 17175267
TI  - Dual response of animals with chronic cyclosporine nephrotoxicity to an acute
      ischemic injury.
AB  - Normal kidneys regenerate after acute injury with little development of chronic
      fibrosis. However, the long-term effects of an acute injury in kidneys with
      established chronic toxicity induced by cyclosporine (CsA) are not entirely
      clear. To study the consequences of an ischemia and reperfusion (IR) injury in
      long-term CsA-treated rats, male Wistar rats (250-300 g) were treated daily with
      CsA (10 mg/kg) or vehicle (olive oil 1 mL/kg) for 28 days. On day 21, ischemia
      was performed by clamping the renal vessel for 1 hour. Blood samples were
      collected on days 0 and 21 (before IR) as well as days 22 and 28. On day 28, the
      kidneys were collected to examine the mRNA expression of MCP-1 by real-time PCR.
      For renal function, serum creatinine levels were measured. Twenty-four hours
      after reperfusion, long-term CsA-treated animals showed better renal function
      compared with the control group, as demonstrated by serum creatinine levels: 2.2
      +/- 0.13 mg/dL vs 2.9 +/- 0.18 mg/dL, respectively (P < .05). However, 1 week
      after IR, the renal function was worse among the long-term CsA-treated group than
      the controls: 1.16 +/- 0.08 mg/dL vs 0.8 +/- 0.09 mg/dL, respectively (P < .05).
      Interestingly, CsA treatment was associated with lower MCP-1 mRNA expression than
      that in the control group: mean MCP-1 mRNA expression 0.58 +/- 0.13 vs 1.02 +/-
      0.12, respectively (P < .05). In conclusion, animals with chronic CsA
      nephrotoxicity were protected from an acute renal injury, possibly through
      decreased chemokine production, although at later time points, renal function was
      clearly impaired, probably by the acceleration of vasculopathy caused by
      nephrotoxicity.

PMID- 17175268
TI  - Ischemic epigenetics and the transplanted kidney.
AB  - The primary purpose of this investigation was to study oxidative demethylation of
      DNA following ischemia/reperfusion injury (I/RI) that putatively influences
      posttransplant gene expression in transplanted kidneys. Our hypothesis was that
      as a result of I/RI, oxidative damage, which is inherent in solid organ
      transplantation, may lead to aberrant demethylation of cytosine-guanine (CpG)
      sites within gene promoter regions of DNA. The methylated CpG sites normally
      contribute to the binding of proteins that render DNA inaccessible to
      transcription factors. Therefore, conversion of methylated cytosines to
      nonmethylated cytosines by oxidative damage in postischemic organs might
      facilitate enhanced gene expression in donor organs by exposing the demethylated
      CpG site in a gene promoter to DNA-binding proteins that enhance gene
      transcription. In this study, we investigated the demethylation of a specific CpG
      within the IFNgamma response element resident in the promoter region of the C3
      gene in the rat kidney. In response to 24 hours of cold ischemia and a subsequent
      2 hours of reperfusion in an isolated ex-vivo circuit, we observed a significant
      change in the ratio of methylated to unmethylated cytosines at this site.
      Epigenetic modifications to donor DNA have not been previously investigated, but
      our own data suggests that they have the potential to modify gene expression
      posttransplantation. Since epigenetic modification may become stable and
      heritable upon mitosis, such changes to the donor organ DNA may persist with
      enormous implications for transplant outcomes.

PMID- 17175269
TI  - Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock
      proteins in 1-hour biopsy from cardiac death donor kidneys.
AB  - AIMS: Since April 1979, 471 kidneys were retrieved from donors after cardiac
      death (DCD) using an in situ regional cooling technique, with excellent renal
      function and good long-term graft survival. However, the precise cascade of
      events following transplantation of DCD kidneys and the influence of ischemia
      reperfusion injury remain unclear. In this study, we performed gene expression
      profiling using 1-hour biopsy samples from DCD kidneys versus those from living
      sources. METHODS: All kidney grafts were procured at our center using an in situ
      regional cooling technique from DCD. Living donor kidneys (LD) were harvested by
      open nephrectomy. All graft biopsies were performed 1 hour after reperfusion (DCD
      n = 8, LD n = 9). We analyzed the expression profile of 20,173 genes. RESULTS:
      One hundred seventy eight genes were up-regulated (>2-fold difference and DCD/LD
      > 1.5) and 120 down-regulated (<1/2-fold and LD/DCD > 1.5) in DCD kidneys.
      Expression of osteopontin (22.5 +/- 2.6-fold DCD vs 7.7 +/- 1.7 LD; P < .001),
      chemokines (CCL4 4.4 +/- 0.7 vs 2.5 +/- 0.3; P < .01), (CCL2 6.0 +/- 1.3 vs 2.8
      +/- 0.5), CXCL1 (9.5 +/- 0.4 vs 2.0 +/- 0.2), and CXCL2 (16.7 +/- 5.3 vs 4.8 +/-
      1.3; P < .05), adhesion molecule (ICAM-1 4.7 +/- 0.7 vs 2.5 +/- 0.4; P < .05),
      and heat shock proteins (HSPA1L 6.7 +/- 0.7 vs 1.6 +/- 0.3, HSPA1A 17.7 +/- 2.6
      vs 2.4 +/- 0.5, HSPA1B 13.3 +/- 0.2 vs 3.0 +/- 0.7, HSPA5 6.7 +/- 0.8 vs 3.2 +/-
      0.3, HSPB1 2.9 +/- 0.2 vs 1.0 +/- 0.1, and HSPH1 19.4 +/- 3.0 vs 5.9 +/- 1.1; P <
      .001) were up-regulated in the kidneys from DCD. CONCLUSION: This report analyzed
      global gene expression using 1-hour biopsy samples from DCD kidneys. These
      results may provide new insight into the identification of novel target genes for
      the development of therapeutic approaches and for determining graft viability of
      kidneys from DCD.

PMID- 17175270
TI  - Endothelial nitric oxide synthase protects transplanted mouse livers against
      storage/reperfusion injury: Role of vasodilatory and innate immunity pathways.
AB  - Endothelial nitric oxide synthase (eNOS) plays a role in microcirculatory and
      immunomodulatory responses after warm ischemia/reperfusion. We hypothesized that
      eNOS is essential to maintain microcirculation, attenuate macrophage infiltration
      and decrease graft injury after liver transplantation. Liver transplantation was
      performed after 18 hours of cold storage in University of Wisconsin (UW) solution
      from wildtype and eNOS-deficient (B6.129P2-Nos3(tm/Unc)/J) donor mice into
      wildtype mice. Serum ALT, necrosis by histology, apoptosis by TUNEL, and
      macrophage infiltration by immunostaining against F4/80 antigen were determined 2
      to 8 hours after implantation. Hepatic microcirculation was investigated after 4
      hours by intravital confocal microscopy following injection of fluorescein
      labeled erythrocytes. After sham operation, livers of wildtype and eNOS-deficient
      mice were not different in ALT, necrosis, apoptosis, macrophage infiltration, and
      microcirculation. After transplantation, ALT increased >3 times more after
      transplantation of eNOS-deficient livers than wildtype livers. Necrosis was >4
      times greater, and TUNEL and F4/80 immunostaining in nonnecrotic areas were 2 and
      1.5 times greater in eNOS-deficient donor livers, respectively. Compared with
      wildtype and eNOS sham-operated mice, sinusoidal blood flow velocity increased
      1.6-fold after wildtype transplantation, but sinusoidal diameter was not changed.
      After transplantation of eNOS-deficient livers, blood flow velocity and
      sinusoidal diameter decreased compared with transplanted wildtype livers. These
      results indicate that donor eNOS attenuates storage/reperfusion injury after
      mouse liver transplantation. Protection is associated with improved
      microcirculation and decreased macrophage infiltration. Thus, eNOS-dependent
      graft protection may involve both vasodilatory and innate immunity pathways.

PMID- 17175271
TI  - The effect of perfusion prior to cold preservation and addition of biliverdin on
      the liver graft from non-heart-beating donors.
AB  - AIM: Our aim was to improve the energy status and viability of a liver graft from
      a non-heart-beating donor (NHBD), we investigated the effects of perfusion prior
      to cold preservation and the addition of an antioxidant, biliverdin. METHODS:
      Rats were divided into five groups: group 1: without 30 minutes warm ischemia
      (WI) and cold preservation (control group); group 2 without WI and with 6 hours
      of cold preservation in UW solution (HBD group); group 3 with WI and cold
      preservation (NHBD group); group 4 with 30 minutes perfusion prior to cold
      preservation (PRE group); and group 5 with addition of biliverdin to precold
      preservation perfusion (BV group). Oxygenated Klebs-Henseleit solution was used
      as the perfusate prior to and after preservation. Portal flow and bile production
      during reperfusion, energy charge (EC), ATP level, GOT, and TNF-alpha were
      measured as well as a histological evaluation. RESULTS: Portal flow of the PRE
      and BV groups during 1 hour of reperfusion was higher than of that the NHBD
      group. Bile production of the PRE group was also higher than that of the NHBD
      group, but bile production in the BV group was comparable to the NHBD group. EC
      of the PRE group was higher than that of the NHBD group prior to and after
      reperfusion. The EC and ATP levels of the BV group after reperfusion were higher
      than those of the NHBD and PRE groups. The GOT and TNF-alpha were reduced in the
      BV group. CONCLUSIONS: Precold preservation perfusion improves the viability of
      grafts from NHBDs. Furthermore, biliverdin exerted an additive effect to
      ameliorate energy status.

PMID- 17175272
TI  - Alterations in protein tyrosine kinase pathways in rat liver following
      normothermic ischemia-reperfusion.
AB  - The phosphoregulation of signal transduction pathways is a complex series of
      reactions that modulate the cellular response to ischemia-reperfusion (I-R). The
      aim of this study was to evaluate the effect of normothermic liver I-R on protein
      tyrosine phosphorylation, production of angiogenic growth factors, and activation
      of signal proteins in tyrosine kinase pathways. A segmental normothermic ischemia
      of the liver was induced in rats by occluding the blood vessels (including the
      bile duct) to the median and left lateral lobes for 120 minutes. Liver extracts
      from either ischemic or nonischemic lobes were prepared at 0, 1, 3, and 6 hours
      after reperfusion. Liver tyrosine phosphorylation of proteins was examined by
      Western blot analysis, whereas vascular endothelial growth factor (VEGF) mRNA was
      analyzed by Northern blot. In ischemic liver lobes, VEGF mRNA and total protein
      levels increased at 1 and 3 hours after reperfusion. Tyrosine phosphorylation of
      the VEGF receptor Flk-1 and the platelet-derived growth factor receptor (PDGF-R)
      was increased only at 1 hour after reperfusion, while c-Src tyrosine
      phosphorylation remained increased at 3 hours and remained up to 6 hours after
      reperfusion. In conclusion, 1-R led to alterations in protein tyrosine
      phosphorylation and increased expression of VEGF in rat liver.

PMID- 17175273
TI  - A novel CCR5/CXCR3 antagonist protects intestinal ischemia/reperfusion injury.
AB  - Chemokines and chemokine receptors have been demonstrated to be critical
      regulators in a variety of physiologic and pathologic immune responses. In
      particular, CCR5 and CXCR3 have been reported to play important roles in the
      alloimmune response. In this study, we investigated the therapeutic efficacy of a
      novel small-molecule compound, TAK779, an antagonist targeting both CCR5 and
      CXCR3 in intestinal ischemia/reperfusion (I/R) injury. We utilized an established
      murine intestinal I/R injury model. TAK779 treatment significantly improved mouse
      survival after 60 minutes of intestinal ischemia. We then examined the local
      intestinal expression of several cytokines and chemokines at 2 hours after
      reperfusion using real-time PCR. TAK779 treatment downregulated the expression of
      several cytokines, including TNF-alpha, IFN-gamma, and IL-4, suggesting that the
      beneficial effect of TAK779 was associated with inhibition of local immune
      activation. We further examined the systemic response after TAK779 treatment.
      Lung tissue damage was significantly prevented by the treatment, as determined by
      lung wet-to-dry weight ratios at 4 hours after intestinal I/R injury. In
      addition, we observed that CCR5 expression in the lung was significantly
      downregulated by the treatment, suggesting that TAK779 inhibited the infiltration
      of CCR5-positive cells into the remote organ. Our data suggest the critical role
      of CCR5 and CXCR3 in intestinal I/R injury and therapeutic efficacy of a novel
      small compound, TAK779, for protection against the intestinal I/R injury.

PMID- 17175274
TI  - Ischemia/reperfusion injury: The role of CD26/dipeptidyl-peptidase-IV-inhibition
      in lung transplantation.
AB  - CD26/Dipeptidyl peptidase (DPP) IV is an integral membrane protein of lymphocytes
      that modulates the activities of chemokines, interleukins, and neuropeptides. We
      investigated the effect of enzymatic DPP IV inhibition on ischemia/reperfusion
      injury after extended ischemia prior to transplantation. MATERIALS AND METHODS:
      We used a syngeneic rat (Lewis) orthotopic left lung transplantation model. In
      the control group (group I), donor lungs were flushed and preserved in Perfadex
      for 18 hours at 4 degrees C, then transplanted and reperfused for 2 hours. Group
      II donor lungs were perfused with and stored in Perfadex +25mol/L AB192 (bis(4
      acetamidophenyl) 1-(S)-prolylpyrrolidine-2(R,S)-phosphonate), a small molecular
      weight DPP IV inhibitor. After 2-hour reperfusion, we measured blood gas, peak
      airway pressure, and thiobarbituric acid reactive substances. RESULTS: Grafts
      from group II versus group I showed a significantly increased oxygenation
      capacity (II: 298.4 +/- 87.6 mm Hg vs 120.9 +/- 48.0, P < .01), lower peak airway
      pressure (11.8 +/- 0.9 mm Hg vs 16.0 +/- 1.4, P < .01), and less lipid
      peroxidation (9.3 +/- 2.0 micromol/L vs 13.8 +/- 1.8, P < .01). CONCLUSION:
      Inhibition of intragraft DPP IV enzymatic activity significantly reduced
      ischemia/reperfusion-associated pulmonary injury, allowing for successful
      transplantation after 18 hours of ischemia.

PMID- 17175275
TI  - Effect of graft preservation and acute rejection on hypoxia-inducible factor-1 in
      rat cardiac allografts.
AB  - Hypoxia plays an integral part in cardiac transplantation as prolonged graft
      preservation is an individual risk factor for the development of cardiac
      allograft vasculopathy (CAV). In this study we characterized the role of hypoxia
      inducible factor-1 (HIF-1) during prolonged graft preservation, ischemia
      reperfusion (I/R), acute rejection, and chronic rejection. Heart transplantations
      were performed from Dark Agouti (DA) to Wister-Furth (allo) or DA to DA (syn)
      rats, without immunosuppression (acute rejection model, harvested at day 5) or
      with cyclosporine (chronic rejection model, harvested at day 60). To study the
      effect of preservation on HIF-1 regulation, normal DA hearts were subjected to
      different cold ischemia times with or without 45 minutes of additional warm
      ischemia. The role of I/R was studied by harvesting syngrafts at different time
      points after reperfusion. Real-time reverse-transcriptase polymerase chain
      reaction quantified total HIF-1 mRNA, while enzyme-linked immunosorbent assay and
      immunohistochemistry quantified and localized HIF-1 protein. Our results show
      that HIF-1 nuclear immunoreactivity is increased during graft preservation and
      I/R leads to loss of nuclear HIF-1 immunoreactivity. Acute rejection induced HIF
      1 in mRNA level. Our findings thus indicated that HIF-1 is activated during
      transplantation and suggested that manipulation of the HIF-1 pathway might reveal
      new therapeutic options to manage CAV.

PMID- 17175276
TI  - Immediate graft function positively affects long-term outcome of renal allografts
      from older but not from younger donors.
AB  - There is disagreement about the impact of delayed graft function (DGF) on renal
      allograft outcome. This may depend on several variables including the age of the
      donor. We evaluated whether DGF could have different effects in recipients of
      kidneys from donors aged more than 60 years versus well-matched recipients of
      younger kidney donors. Patients were retrospectively subdivided into 3 groups.
      Immediate graft function (IGF), DGF without dialysis (DGF-ND), DGF requiring
      dialysis (DGF-D). DGF-ND and DGF-D occurred more frequently among 198 older than
      198 younger donors (P = .016 and P = .044, respectively). The 5-year patient (96%
      vs 93%) and pure graft (96% vs 89%) survivals were significantly better in
      younger recipients, while the incidence of acute rejection was similar. After a
      mean follow-up of 66 +/- 44 months in older donor recipients, the graft survival
      was significantly better among IGF than patients in the DGF-ND (P = .046) or DGF
      D (P = .003) groups. Instead, in younger recipients there was no difference in
      graft survival between IGD and DGF-ND. Only patients with DGF-D showed a
      significantly worse outcome. Upon multivariate analysis of older donors, their
      recipients, showed the pattern of graft function recovery to be the only variable
      associated with allograft outcome. Instead in younger donor recipients, acute
      rejection and time on dialysis were the main variables associated with a poor
      outcome. In older donor recipients, DGF was an independent variable associated
      with a poor graft outcome. In younger donor recipients, duration of dialysis and
      rejection were the most important predictors of poor graft outcomes.

PMID- 17175277
TI  - Should we discard the renal allografts from cardiac death donors that have total
      ischemic time longer than 24 hours?
AB  - PURPOSE: The objective of this study was to investigate the outcome of
      transplantation using kidney grafts donated after cardiac death (DCD) with a
      total ischemic time (TIT) longer than 24 hours. PATIENTS AND METHODS: We followed
      373 kidneys recovered from DCD donors and transplanted at 41 centers. All kidneys
      were procured from uncontrolled DCD donors. Grafts were classified into two
      groups according to TIT. We recorded renal function and duration of the survival
      period for each graft. RESULTS: Fifty-three grafts had a TIT longer than 24 hours
      (group 1). The other 320 grafts had a TIT less than 24 hours (group 2). The
      number of never functioning grafts were three in group 1 (5.7%) and 17 in group 2
      (5.3%). Delayed graft function (DGF) occurred in 44 group 1 (83.0%) and 254 group
      2 kidneys (79.4%) for intervals of 13.5 +/- 12.6 versus 10.9 +/- 12.6 days,
      respectively. Graft survival rates at 3, 5, and 10 years posttransplant were
      84.9%, 73.0%, 64.1% for group 1, and 76.3%, 69.9%, 57.1% for group 2. In a Cox
      proportional hazards model, TIT longer than 24 hours was not a significant
      independent risk factor. CONCLUSION: Our results showed that even kidneys with
      TITs of over 24 hours yielded comparable results despite a higher incidence of
      DGF.

PMID- 17175278
TI  - Microscopic intrarenal particles after pulsatile machine preservation do not
      adversely affect outcomes after renal transplantation.
AB  - INTRODUCTION: Our center has recently observed foreign carbohydrate-appearing
      particles (FP) on transplant postreperfusion biopsy specimens: (PRBx). METHODS:
      To further characterize FPs, we reviewed all renal transplant RBx (30-45 minutes)
      performed between September 1, 2004 and December 3, 2005. Donor, preservation,
      and outcome variables were collected among patients with FP. RESULTS: A total of
      135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]).
      Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine
      perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United
      States) with Belzer MP solution (Trans Med, Elk River, Minn, United States).
      Donor age was 39.8 +/- 15.7 years. Terminal creatinine level was 1.45 +/- 0.8
      mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold
      ischemia time was 28.8 +/- 9.1 hours with 14.3 +/- 5.1 hours of MP. In 13 of 15
      patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35).
      CHARACTERISTICS OF FP: Particles were 10-30 mu and globular in shape. FP were not
      visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff
      (PAS) positive and were refractile under polarized light. FP were seen
      segmentally within glomerular capillaries in all cases and in peritubular
      capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi
      or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had
      a biopsy within the first week with no identifiable FP. OUTCOMES: Recipient age
      was 45.3 +/- 11.6 years. Eight patients (53.3%) had delayed graft function.
      Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine
      level was 1.59 +/- 0.35 mg/dL. One graft was lost to early thrombosis in a
      patient with a hypercoagulable state and 1 patient died of sepsis at 2 months.
      All remaining 13 patients are alive with excellent graft function at a median
      follow-up of 6.7 months (range, 3-17 months). CONCLUSIONS: Microscopic intrarenal
      particles may be seen on DD kidney PRBx after MP. These FPs likely originate from
      surgical gloves. FPs are too small to be captured by standard filters but clear
      spontaneously and do not have deleterious effects on renal function or outcomes.

PMID- 17175280
TI  - Selective use of expanded criteria donors for renal transplantation with good
      results.
AB  - Increasing demand for renal transplants has stimulated expanded criteria for the
      use of deceased donors. Recently an official category of "Expanded Criteria
      Donors" (ECD) was designated by UNOS. This category included any deceased donor
      (1) greater than age 60 years or (2) age 50 to 59 years with any two of: (a)
      creatinine greater than 1.5 mg/dL (b) cerebrovascular accident cause of death, or
      (c) hypertension history. It has been anticipated that at 3 years, 70% of ECD
      kidneys with serum creatinine greater than 1.5 would be lost. We reviewed our
      experience with the use of this type of kidney prior to the era of officially
      designated ECD. Survival rates and serum creatinines were compared to standard
      criteria donor recipients for the same time period whose donor was greater than
      50 years of age and correlated with biopsies. From 1996 to 2003, 341 deceased
      donor kidneys were transplanted at our center. Of these, 37 were ECD kidneys and
      46 were standard criteria donors kidneys. Four pretransplant biopsies had greater
      than 20% sclerosed glomeruli. Four donors had 0% to 25% arteriosclerosis
      pretransplant; on postperfusion biopsy, eight had 0% to 25% arteriosclerosis,
      while three had 25% to 50%. The mean donor age was 61 years; mean recipient age
      was 54 years; recipient sex was 57% male, and 54% of the recipients were African
      American. At 1, 2, and 3 years posttransplant, there was no significant
      difference between the two groups in serum creatinine, graft survival, or patient
      survival. Despite using ECD donors, good long-term function can be obtained,
      particularly if selectivity is exercised.

PMID- 17175279
TI  - Is pulsatile perfusion necessary for renal transplantation engrafting kidneys
      from cardiac death donors?
AB  - BACKGROUND: There has been a considerable literature describing the use of
      pulsatile perfusion (PP) to evaluate the efficacy of organs from deceased donors.
      Since 1979, we recovered 469 kidneys from deceased donors after cardiac death
      (DCDs), using an in situ regional cooling technique and preservation by simple
      cold storage. In this study, the posttransplantation outcomes as well as long
      term survivals of renal grafts from DCDs were compared with PP data in the recent
      literature. MATERIALS AND METHODS: We compared our recent data with 176 kidneys
      recovered between 1993-2002 using an in situ regional cooling technique. Patient
      and graft survivals were compared with those from the Scientific Registry of
      Transplant Recipients (SRTR) database. RESULTS: Following transplantation, 4.5%
      of the grafts never recovered; 10.3% of the grafts showed immediate renal
      function; 85.2% of the grafts had delayed graft function (DGF) with an average
      acute tubular necrosis (ATN) period of 13.1 days compared with 54.3% DGF from DCD
      using PP. Graft survival rates at 1, 3, 5, and 10 years were 90.8%, 86.5%, 77.8%,
      and 69.0%, respectively, compared with 89% at 1 year and 80% at 3 years reported
      for DCD by the SRTR in which almost 30% of the grafts underwent PP. CONCLUSIONS:
      Although PP seemed to have some advantage to decrease the DGF ratio, an in situ
      regional cooling technique with simple cold storage may provide excellent graft
      function and long-term graft survival as well as having benefits in cost and
      transportation.

PMID- 17175281
TI  - Multi-array antibody screening in detecting antibodies to mismatched HLA in
      patients awaiting a second transplant.
AB  - Effective identification of HLA specificities to which a prospective transplant
      recipient has antibodies depends on how effective the most sensitive assay is in
      detecting these antibodies. To ascertain the assay's efficacy, the results of
      antibody screening of patients on the waiting list for a second transplant were
      studied. A commercially available panel of fluoro-coded microbeads coated with
      multiple and single purified class I or II HLA antigens was used with flow
      cytometry to detect antibodies in human serum (LABScreen, One Lambda, Canoga
      Park, Calif, USA). A total of 112 HLA-A, B, and DR mismatches between donors and
      recipients were present among 34 patients. Antibodies to 56% of the mismatches
      were detected with 67% of the HLA-A, 38% of the HLA-B, and 63% of the HLA-DR
      mismatches detected, respectively. Thirty percent of the patients had antibodies
      to all of the mismatched HLA, 43% had antibodies to some, and 27% did not develop
      antibodies to any of the mismatched antigens. Among patients who developed
      antibodies to all of the mismatched HLA, 60% had had a transplant nephrectomy.
      Only 11% of patients who had no antibodies detected to mismatched HLA had had a
      transplant nephrectomy and 44% of them were still on immunosuppression. Using the
      Matchmaker program developed by Duquesnoy, the latter group of patients had a
      sufficient number of triplet mismatches that could have resulted in an antibody
      response. All of the undetected antibodies had been identified in other patients
      in this group. The assay used in this study to detect antibodies is considered
      the most sensitive one available. Nonetheless, antibodies to slightly less than
      half of the mismatched HLA antigens were not detected. It appears that the assay
      system is capable of detecting the antibodies, since in other patients with the
      same mismatched HLA, antibodies were detected. It is likely that the recipients
      could develop antibodies since there was a sufficient degree of disparity in the
      HLA of donors and recipients. Antibodies were more likely to be detected when
      there had been a transplant nephrectomy and the absence of immunosuppression.
      There was no way of knowing whether we were missing detecting antibodies or if
      they were not present. The results of this study have important implications with
      respect to utilizing "unacceptable antigens" in an allocation system for patients
      awaiting a second transplant.

PMID- 17175282
TI  - Non-heart-beating kidney transplantation: 6-year outcomes.
AB  - Non-heart-beating donor kidneys (NHBD) are being used to increase the donor pool
      due to the scarcity of cadaveric heart beating donors (HBD). We evaluated the
      long-term outcomes of renal transplantation using NHBD kidneys, comparing the
      first 100 NHBD kidneys transplanted at our facility to the next consecutive
      cadaveric HBD kidneys for graft survival, recipient survival, and quality of
      graft function. Recipient survival (P = .22) and graft survival (P = .19) at 6
      years did not differ between recipients of NHBD (83%, 80%) and HBD (89%, 87%)
      kidneys. Quality of graft function using the mean glomular filtration rates were
      significantly lower in the NHBD group up to 3 months following discharge (41 +/-
      2 vs 47 +/- 2, P = .007) but were then comparable up to 6 years following
      transplantation (43 +/- 5 vs 46 +/- 4, P = .55).

PMID- 17175283
TI  - Long-term outcome of renal transplantation from marginal donors.
AB  - Long-term survival of kidneys from suboptimal donors is known to be not as good
      as that from optimal ones. However, the shortage of donors has led many
      transplant centers to consider accepting older donors with comorbidities. We
      analyzed 238 patients who received deceased donor renal transplants in the period
      2000-2005. The recipients were matched to be no more than 15 years older or
      younger than the corresponding donors. Among them 125 received a single and 18 a
      double transplantation from donors considered marginal, according to UNOS
      criteria for expanded criteria donor (ECD). Most kidneys were evaluated with a
      pretransplant biopsy, using the scoring system introduced by Karpinski in 1999.
      The analysis indicated clearly better results in the non-ECD group: both patients
      and graft survival rates were 10% higher at 1, 2, and 3 years. However, the ECD
      group showed satisfactory outcomes, confirming the utility of this procedure. The
      long-term survival rates of single or double grafts from marginal donors are
      satisfactory, confirming the practice of allocating kidneys after a
      preimplantation histological evaluation, allowing expansion of the donor pool and
      providing older patients access to the waiting lists.

PMID- 17175284
TI  - Renal graft function after prolonged agonal time in non-heart-beating donors.
AB  - To deal with the increasing gap between organ demand and supply for kidney
      transplantation, many centers have started to use non-heart-beating (NHB) donors.
      When we initiated our program to utilize kidneys from such donors in 1998, we had
      no protocol for the maximal agonal period. This however was audited in
      retrospect. Our current wait time is now a maximum of 5 hours. Concern has been
      expressed in the past about possible deterioration in the quality of the organs
      with a protracted agonal time. We aimed in this study to examine the effect of
      prolonging agonal period on the quality of kidneys retrieved from Maastricht
      category III donors: A total of 40 kidneys were transplanted from 29 category III
      donors between 1998 and 2004. Eleven kidneys had donor agonal times of >5 hours;
      the remainder, agonal times <5 hours. Both groups were matched for donor and
      recipient factors. The mean glomerular filtration rates at 12 months for <5 hours
      versus >5 hours agonal time were 43.8 +/- 4.4 versus 49.8 +/- 5.8, respectively
      (P = .24) and at 24 months, 46.83 +/- 8.99 versus 37.67 +/- 3.85, respectively (P
      = .24). In conclusion, intermediate graft function is comparable to ones with
      shorter agonal time, although we await long-term results.

PMID- 17175285
TI  - Diabetic donors as a source of non-heart-beating renal transplants.
AB  - Due to the organ shortage, many renal transplantation centers attempt to increase
      the donor pool by using non-heart-beating donors (NHBDs). These kidneys are
      generally regarded as "marginal" grafts. Many centers do not consider
      transplantation from an NHBD with a history of diabetes as it is a more
      suboptimal donor. We began our NHBD program in 1998 and have performed 5 renal
      transplants from diabetic NHBDs. Viability testing identified kidneys suitable
      for single or dual transplantation. Although kidneys from brain stem dead donors
      with diabetes have been used successfully, our data suggested that kidneys from
      diabetic NHBDs can also be used although we still need long-term results.

PMID- 17175286
TI  - Evaluation of Epstein-Barr virus (EBV) antibody screening of organ donors for
      allocation of organs to EBV serostatus matched recipients.
AB  - OBJECTIVE: Posttransplant lymphoproliferative disorder (PTLD) is a life
      threatening complication following organ transplantation. The greatest risk is
      seen in Epstein-Barr virus (EBV)-seronegative patients receiving allografts from
      EBV-seropositive donors. The severity and frequency of PTLD are particular
      concerns for pediatric patients, who frequently are EBV negative and hence more
      likely to be EBV infected from an EBV-positive organ donor. The aim of this study
      was to analyze the EBV serostatus of deceased organ donors and to assess the
      likelihood of recipient/donor matching for EBV serostatus. MATERIALS AND METHODS:
      Sera obtained from local deceased organ donors for the period 2004-2005 were
      retrospectively tested for EBV viral capsid antigen (VCA) IgG and IgM antibodies
      by an enzyme-linked immunosorbent assay (ELISA). The analysis included only data
      from those donors who were tested using a pretransfusion specimen (n = 459). The
      influence of various factors on the EBV serostatus of the donor was assessed,
      including age, gender, ethnicity, and cytomegalovirus (CMV) serostatus of the
      donor. RESULTS: Overall, only 27 (6%) of the 459 donors were EBV seronegative,
      with 94% being positive for IgG antibodies to EBV. A higher percentage of the EBV
      seronegative donors were younger donors (age < or =35 years), compared with EBV
      seropositive donors, 74% (n = 27) vs 31% (n = 432), P < .0001. A higher
      percentage (85%) of the younger (age < or =35 years) EBV-seronegative donors (n =
      20) were also CMV seronegative. There was also a greater likelihood for the
      younger (age < or =35 years) CMV-seronegative donors to be EBV seronegative,
      compared with the older (age >35 years) CMV-seronegative donors, 20% (n = 83) vs
      1% (n = 93), P < .0001. There was no influence of other factors examined on EBV
      serostatus. CONCLUSIONS: EBV-seronegative organ donors are infrequent and
      therefore provide only a limited supply of organs for patients in need of them.
      The higher frequency of EBV-seronegative donors being the younger donors will
      benefit the pediatric patients who have the greatest need for an EBV serostatus
      matched organ from a younger donor. Recent policy changes at the United Network
      for Organ Sharing (UNOS) giving priority to pediatric patients for kidneys from
      younger donors (age < or =35 years) and prospective EBV testing of donors will be
      helpful in the appropriate allocation of these organs.

PMID- 17175287
TI  - Comparison of techniques of vascular control in laparoscopic donor nephrectomy:
      The leicester experience.
AB  - BACKGROUND: The objective of this study was to compare the safety and efficacy of
      three different methods to secure the renal vessels during laparoscopic donor
      nephrectomy (LDN). METHODS: Vessel lengths and intraoperative vascular
      complications were compared in a prospective series of 106 LDNs in which the
      vessels had been secured using a stapling device, metal clips, or polymer clips.
      RESULTS: One hundred six patients underwent LDN (right = 25, left = 81). Renal
      vein lengths were not significantly different after stapling or using polymer
      clips (36 +/- 10 vs 37 +/- 9 mm; P = .463). Renal arterial length was shorter
      after stapling (30 +/- 7 mm) compared with both endoclips (34 +/- 10 mm; P =
      .030) and polymer clips (34 +/- 8 mm; P = .030). There was one major arterial
      bleed in the endoclip group, one episode of stapler malfunction, but no adverse
      events with polymer clips. CONCLUSION: Polymer clips are safe and yield greater
      vessel lengths during LDN.

PMID- 17175288
TI  - Outcome of laparoscopic live donor nephrectomy in 2005: National survey of
      Japanese transplantation centers.
AB  - The increased acceptance of laparoscopic nephrectomy (LN) has been a driving
      force for live donor kidney transplantation. However, the outcomes of LN in live
      donors has not yet been clarified in Japan. In this study, we surveyed 125
      Japanese kidney transplantation centers to investigate the current status of live
      donor LN. Of 125 centers, the 98 that responded had performed 695 live donor
      nephrectomies. Among these centers, 43 had performed LN. Among the 695
      nephrectomies, 441 donors had undergone LN and 254, open nephrectomies. In 43
      centers, 16 were performed as hand-assisted (HA) LN; 20, non-HA; 3, both HA and
      non-HA; and 5 laparoscope-assisted. Ten centers used a peritoneal approach; 30, a
      retroperitoneal; and 3, both. In 441 LN donors, 1 had a life-threatening
      complication of deep venous thrombosis and survived. Blood transfusions were
      performed in 7 donors. Open conversions from LN were necessary in 24. Minor
      complications not requiring prolonged hospital stay were reported in 52. The
      mortality of LN was zero. In contrast, among the 441 recipients, 1 case was
      reported as primary nonfunction after venous misadventure in the operation and 30
      recipients needed hemodialysis after transplantation because of delayed graft
      function. Urinary tract complications were noted in 11 recipients. This survey
      presented the current status of the procedure, providing a base for informed
      consent from potential donors.

PMID- 17175289
TI  - Renal autotransplantation for the treatment of complex renovascular hypertension.
AB  - OBJECTIVE: In individuals with complicated renal vascular disease, renal
      autotransplantation has been used as an alternative to percutaneous transluminal
      angioplasty, which may be unsuccessful or hazardous in these situations. We
      evaluated the outcomes of renal autotransplantation. PATIENTS AND METHODS:
      Between February 1989 and December 2005, we performed 5 renal autotransplantation
      procedures. The surgical strategy included renal explantation, ex vivo renal
      preservation, ex vivo reconstruction of the renal artery if necessary, and renal
      heterotopic autotransplantation. RESULTS: The study subjects (3 men and 2 women)
      exhibited one of the following indications for surgery: fibromuscular dysplasia
      (2 patients), Takayasu's arteritis (1), or atherosclerosis (2). All patients
      exhibited uncontrolled hypertension before renal autotransplantation. Renal
      arteries of patients were anastomosed either to the external or internal iliac
      arteries or to both when there were multiple renal arteries. The renal vein was
      anastomosed end-to-side to the external iliac vein, and ureteral reimplantation
      was not performed. Mean posttransplantation follow-up was 9.8 +/- 5.7 years
      (range, 1-16 years). Mortality and morbidity were not observed during the follow
      up, and hypertension and renal function normalized or improved in all 5 patients.
      CONCLUSIONS: Renal autotransplantation is a highly effective procedure to treat
      complex renovascular lesions; ex vivo renal repair is a safe and effective
      surgical procedure in the clinical setting.

PMID- 17175290
TI  - Desensitized renal transplant recipients show reduced cellular responses to in
      vitro challenge.
AB  - Intravenous immunoglobulin (IVIG) desensitization protocols permit
      transplantation of sensitized renal recipients against alloantibody
      incompatibility barriers. It appears that IVIG induces a sustained down
      regulation of alloantibody that facilitates crossmatch compatibility. However,
      the consequence of desensitization upon cellular immunity has not been addressed.
      We compared in vitro proliferative responses and cytokine expression between
      desensitized transplant recipients (IVIG) and non-IVIG-treated patients
      (controls). Eleven patients who were crossmatch-incompatible with living donors
      underwent treatment with IVIG and plasmapheresis. Nine patients converted to
      negative crossmatches and were transplanted. With a mean follow-up time of 17.6
      +/- 6.7 months, graft survival is 100%. Peripheral mononuclear cells were
      collected 12.5 +/- 9 months after transplantation and tested for proliferative
      response and cytokine elaboration following challenge with staphylococcal
      enterotoxin b (SEB) and donor-specific mixed lymphocyte reaction (dMLR).
      Proliferative reactions were 90% lower (P < .05) among IVIG versus controls in
      response to SEB and dMLR challenge. Cytokine response to SEB challenge was
      equivalent (P = NS) between IVIG and controls. In contrast, cytokine elaboration
      was 60% lower (P < .05) for IVIG versus controls in response to dMLR. One year
      after renal transplantation, desensitized patients showed in vitro
      hyporesponsiveness to superantigen and donor-specific challenge. This suggests
      that IVIG promotes a down-regulation in cellular immunity that may facilitate
      good graft outcome.

PMID- 17175291
TI  - Varicella zoster virus serostatus before and after kidney transplantation, and
      vaccination of adult kidney transplant candidates.
AB  - In recent years we observed 3 lethal primary varicella infections in adult kidney
      transplant recipients. Therefore, we wondered how many of our adult renal
      transplant patients were not protected against varicella zoster virus (VZV), and
      therefore were at risk for such a primary infection. We also studied the
      prevalence of VZV seronegativity in the adult patients on our waitlist for kidney
      transplantation. Finally, we vaccinated these seronegative patients with an
      attenuated live vaccine. Sera were obtained from 854 transplanted patients, and
      from 286 candidates on the waitlist for kidney transplantation. We observed that
      2.1% of our renal transplant recipients and 3.2% of the patients on the waitlist
      were seronegative for VZV. We vaccinated 11 seronegative patients on the waitlist
      twice without side effects. In 7 of 11 patients this resulted in a positive
      serologic response. In conclusion, the prevalence of VZV seronegativity was low
      both in renal transplant recipients (2%) and in patients on the waitlist (3%).
      Vaccination of transplant candidates resulted in a moderate efficiency of 64%.

PMID- 17175293
TI  - Putative antibody-mediated rejection with C4d deposition in HLA-identical, ABO
      compatible renal allografts.
AB  - We sought evidence for non-MHC antibody-mediated rejection in renal allografts by
      a systematic study of rejected HLA-identical sibling renal allografts. Among 162
      recipients of HLA-identical, ABO-compatible sibling donor kidneys transplanted at
      the Massachusetts General Hospital from 1964 to 2005, we identified 15 grafts
      that were lost from rejection and two additional grafts with reversible acute
      rejection, which provided 30 samples for study. All samples were stained for C4d
      by immunofluorescence in frozen tissue (n = 7) or by immunohistochemistry in
      paraffin embedded tissues (n = 10). We found that two of 17 grafts had positive
      C4d staining of peritubular capillaries. Histology revealed acute antibody
      mediated rejection in one and acute cellular rejection type 1 in the other. Both
      grafts were matched at HLA-A, B, and C loci and had a nonreactive mixed
      lymphocyte response. Genotyping and serological analysis were not available.
      Compared with a published series, C4d+ irreversible rejection was more common in
      HLA nonidentical than HLA-identical grafts (75% vs 6.7%, respectively, P < .002).
      We conclude that antibody-mediated rejection, presumably due to non-MHC antigens
      other than ABO-blood groups does occur, but infrequently. This may account for
      some of the HLA antibody negative cases that develop antibody-mediated rejection.

PMID- 17175292
TI  - Quantitative detection of promoter hypermethylation as a biomarker of acute
      kidney injury during transplantation.
AB  - Aberrant promoter hypermethylation, also known as epigenetics, is thought to be a
      promising biomarker approach to diagnose malignancies. Kidney repair after injury
      is a recapitulation of normal morphogenesis, with similarities to malignant
      transformation. We hypothesized that changes in urine epigenetics could be a
      biomarker approach during early kidney transplant injury and repair. We examined
      urine DNA for aberrant methylation of two gene promoters (DAPK and CALCA) by
      quantitative methylation-specific polymerase chain reaction from 13 deceased and
      10 living donor kidney transplant recipients on postoperative day 2 and 65
      healthy controls. Results were compared with clinical outcomes and to results of
      the kidney biopsy. Transplant recipients were significantly more likely to have
      aberrant hypermethylation of the CALCA gene promoter in urine than healthy
      controls (100% vs 31%; P < .0001). There was increased CALCA hypermethylation in
      the urine of deceased versus living donor transplants (21.60 +/- 12.5 vs 12.19 +/
      4.7; P = .04). Furthermore, there was a trend toward increased aberrant
      hypermethylation of urine CALCA in patients with biopsy-proven acute tubular
      necrosis versus acute rejection and slow or prompt graft function (mean: 20.40 +/
      6.9, 13.87 +/- 6.49, 17.17 +/- 13.4; P = .67). However, there was no difference
      of CALCA hypermethylation in urine of patients with delayed graft function versus
      those with slow or prompt graft function (16.9 +/- 6.2 vs 18.5 +/- 13.7,
      respectively; P = .5). There was no aberrant hypermethylation of DAPK in the
      urine of transplant patients. Urine epigenetics is a promising biomarker approach
      for acute ischemic injury in transplantation that merits future study.

PMID- 17175294
TI  - Does endothelial chimerism correlate with renal allograft rejection?
AB  - BACKGROUND: The blood vessels of a transplanted organ are an interface between
      the donor and the recipient. The endothelium is believed to be a major target for
      graft rejection. After transplantation endothelial cells of a transplanted organ
      may be of recipient origin. OBJECTIVES: In this study we sought to determine
      whether endothelial chimerism correlates with graft rejection. METHODS: Biopsy
      samples from 34 renal transplants of female recipients who received kidneys from
      male donors were studied for the presence of endothelial cells of recipient
      origin. Formalin-fixed, paraffin-embedded tissue sections of renal biopsy samples
      were examined by fluorescence in situ hybridization (FISH) for the presence of
      endothelial cells containing two X chromosomes, using a biotinylated Y-chromosome
      probe and digoxigenin-labeled X-chromosome probe. RESULTS: The FISH methods
      identified endothelial cells of recipient origin. Endothelial chimerism was
      common, irrespective of rejection. Its presence was focal with these elements,
      coexisting in the biopsy. CONCLUSIONS: We observed no correlation between the
      percentage of recipient endothelial cells among vascular elements and the type of
      graft rejection (P > .05).

PMID- 17175295
TI  - Resistin, a new adipokine, is related to inflammation and renal function in
      kidney allograft recipients.
AB  - BACKGROUND: Among patients without chronic kidney disease, resistin, an
      adipocytokine, has been related to inflammatory markers, coronary artery disease,
      and cardiovascular disease in the metabolic syndrome. Moreover, resistin up
      regulates adhesion molecules. Since inflammation and endothelial cell damage or
      injury are invariably associated with thrombosis, atherosclerosis, and their
      major clinical consequences, resistin may play a role to link inflammation and
      CVD. The aim of this study was to correlate resistin with markers of inflammation
      and endothelial cell injury in 96 kidney allograft recipients. METHODS: We
      measured resistin and the following markers of endothelial function/injury: vWF,
      thrombomodulin, VCAM, hsCRP, tumor necrosis factor alpha (TNFalpha), and
      interleukin-6 (IL-6). RESULTS: Triglycerides, CRP (assessed by high-sensitivity
      method), phosphate, creatinine, IL-6, TNFalpha, vWF, prothrombin fragments 1 + 2,
      and resistin were elevated among kidney transplant recipients compared with the
      control group. Kidney allograft recipients with coronary artery disease displayed
      significantly higher resistin levels than those in patients without this
      complication. Upon univariate analysis resistin levels in kidney allograft
      recipients were related to hsCRP, IL-6, thrombomodulin, red blood cell count,
      white blood cell count, platelet count, creatinine, urea, VCAM, CSA, dose and
      eGFR. Upon multiple regression analysis, resistin was independently related only
      to creatinine, hsCRP, and white blood cell count in kidney allograft recipients.
      CONCLUSIONS: The relation of elevated resistin levels to markers of inflammation
      may represent a novel link between these conditions and adipocytokines. Renal
      function was a major determinant of elevated resistin in kidney allograft
      recipients.

PMID- 17175296
TI  - Clonal T-large granular lymphocyte proliferation in solid organ transplant
      recipients.
AB  - Large granular lymphocytic (LGL) leukemia is a rare disorder, usually caused by
      clonal proliferation of CD3+ CD57+ T-LGL cells. T-cell clonality is confirmed by
      rearrangements of the T-cell receptor (TCR) gene. Characteristic features of T
      LGL leukemia include neutropenia, anemia, and constitutional symptoms such as
      fatigue. Many solid organ transplant recipients experience similar symptoms and
      have neutropenia and anemia often attributed to immunosuppressive therapy. The
      purpose of this study was to determine the prevalence of T-LGL proliferation in
      solid organ transplant recipients and demonstrate its association with leukopenia
      and anemia. Twenty-three cardiac and renal transplant patients were evaluated by
      peripheral smear examination, flow cytometry, and TCR gene rearrangement study by
      polymerase chain reaction. Ten of 14 (71%) cardiac transplant patients and 4 of 9
      (44%) renal transplant patients, without evidence of either allograft rejection
      or a viral syndrome, were found to have clonal expansion of T-LGL cells.
      Constitutional symptoms were present in 30% of these patients. Anemia of <10 g/dL
      was seen in 75% of renal transplant and 10% of cardiac transplant patients. None
      of these patients had significant neutropenia defined as absolute neutrophil
      count of 1500 mu/L. Most of the patients did not require any specific therapeutic
      intervention. Although TCR gene rearrangement is considered a hallmark of T-LGL
      leukemia, we believe that this monoclonality is not a true form of posttransplant
      lymphoproliferative disorder. Constant antigenic stimulus from the allograft may
      be the underlying etiology of clonal expansion and may contribute to cytopenias
      and fatigue seen in transplant patients.

PMID- 17175297
TI  - The presence of B-cell nodules does not necessarily portend a less favorable
      outcome to therapy in patients with acute cellular rejection of a renal
      allograft.
AB  - The presence of B-cell nodules in kidney biopsies of patients undergoing acute
      renal allograft rejection has been reported to be associated with glucocorticoid
      resistance and a high risk of graft failure. In an attempt to corroborate this
      observation, biopsies of renal transplants that evidenced Banff grade I A acute
      rejection were examined for the presence of B- or T-cell nodules, the detection
      of which was correlated with the therapeutic response. Biopsies from 14
      consecutive renal transplant recipients with a diagnosis of acute cellular
      rejection were examined for the presence of T (CD3-positive) or B (CD20-positive)
      cells by immunohistochemistry. All patients were biopsied because of a rise in
      serum creatinine. No biopsy showed evidence of acute humoral rejection.
      Immunofluorescence microscopy was negative for C4d deposition in peritubular
      capillaries. There were no neutrophils in the peritubular or glomerular
      capillaries. Five patients had T-cell nodules; four had B-cell nodules; three had
      both T- and B-cell nodules; two had no nodules. All biopsies contained CD3
      positive cells in the tubules and in the interstitium. In all but one of the
      patients, episodes of acute rejection were treated with steroids (one received
      thymoglobulin). Furthermore two patients received mycophenolate mofetil and one,
      sirolimus. There were no significant differences among the groups in either the
      initial creatinine or the creatinine after therapy. The presence of B-cell
      nodules in renal allograft biopsies of patients experiencing acute cellular
      rejection did not portend a less favorable outcome.

PMID- 17175298
TI  - Kidney transplantation in patients receiving dialysis treatment for more than 10
      years.
AB  - In the present single center study, we analyzed 277 kidney transplant patients
      (procedures performed between February 1984 and February 2006) to determine the
      impact of long-term dialysis on kidney transplant outcomes. Forty-four had been
      treated prior to renal transplantation with dialysis for more than 10 years
      (range, 10.0-32.5 years, average, 16.6 years; Group I), while the remaining 233
      recipients showed an average end-stage renal disease period of 2.8 years (range,
      0-9.8 years; Group II). There were no significant differences in patient
      survivals between the 2 groups: 97.3% vs 97.4% at 1 year; 85.7% vs 92.4% at 5
      years; 85.7% vs 90.7% at 10 years (P = .2347). Five Group I patients died: 2 from
      infections, 2 from liver dysfunction, and 1 from cerebral bleeding. These causes
      of death were similar to those among Group II patients. Graft survival was not
      significantly different between the 2 groups: 95% vs 88.8% at 1 year; 75.5% vs
      76.5% at 5 years; 75.5% vs 65.5% at 10 years (P = .6264). Our results suggested
      that dialysis treatment for more than 10 years did not have negative effects on
      posttransplantation patient and graft survival.

PMID- 17175299
TI  - Outcome of renal allograft in Turkish patients with pretransplantation hepatitis
      C virus infection.
AB  - BACKGROUND: The aim of the present study was to investigate the impact of
      hepatitis C virus (HCV) infection on the long-term survival of renal transplant
      recipients. METHODS: Outcomes and survivals among 325 patients who received renal
      allografts from July 1991 to September 2005 were compared between those known to
      have pretransplantation HCV infection (Group I, HCV+ group, n = 33) versus a
      matched cohort of those without this infection (Group II, HCV- control group, n =
      33). Allograft performance, liver function, cholesterol, and glucose levels were
      determined both at transplantation and at a mean of postgrafting year 8. A one
      way analysis of variance (ANOVA) statistical method was used for multivariate
      analysis. RESULTS: Thirty-three patients (10.15%, 19 women and 14 men) were
      positive for HCV antibody. The mean follow-up period was 8 years (range, 0.5-14
      years). The mean survival rates were similar in Groups I and II (96.6% and, 100%,
      respectively). Although the allograft survival rate was lower in Group I (84.8%
      vs 90.9%), the rejection rate among the HCV- group was 6%; only 1 patient died of
      hepatic failure. In spite of a significant rise in both total and direct
      bilirubin values (P < .01) in both groups, we failed to observe an adverse effect
      on graft survival. A significant rise in the fasting glucose level was seen in
      both HCV+ and HCV- patients. CONCLUSIONS: Chronic HCV infection before
      transplantation did not have a significant impact on graft survival or mortality
      compared with noninfected patients.

PMID- 17175300
TI  - Retrospective study of the effects of cyclosporine in comparison with
      azathioprine on renal transplant recipients infected with hepatitis C virus.
AB  - A recent report noted that cyclosporine (CsA) inhibits replication of the
      hepatitis C virus (HCV) in vitro. Thus, CsA may be a superior immunosuppressant
      for renal transplant recipients infected with HCV. In the present retrospective
      study, we assessed whether CsA reduced the clinical impact of HCV infection among
      those patients. A total of 405 renal transplants were performed between 1973 and
      2005, of whom we studied 189 who received CsA-based immunosuppression (CsA group)
      vs 108 who received an azathioprine-based regimen (AZA group). There were 44
      HCVAb carriers and 145 noncarriers in the CsA group, and 41 carriers and 67
      noncarriers in the AZA group. Our results showed that patient survival rate was
      significantly worse among HCVAb carriers than among noncarriers, as the overall
      survival rates were 82.9% and 90.9%, respectively, after 10 years and 71.5% and
      85.7%, respectively, after 20 years (P = .0003). Patient survival rates were also
      significantly worse in HCVAb carriers than in noncarriers in both groups, which
      were 83.2% and 95.0%, respectively, after 10 years, and 74.7% and 88.8%,
      respectively, after 20 years (P = .0147) in the CsA group, and 82.9% and 83.6%,
      respectively, after 10 years and 70.7% and 80.6%, respectively, after 20 years (P
      = .0171) in the AZA group. Conversely, no significant difference was seen in
      patient survival rate for HCVAb carriers between the two groups (83.2% vs 82.9%
      at 10 years, and 74.7% vs 70.7% at 20 years, P = .8195). Our results confirmed
      that HCV infection has a negative impact on the long-term survival of renal
      transplant patients who receive either a CsA-based or an AZA-based regimen,
      suggesting that CsA does not have a positive impact on HCV carriers.

PMID- 17175301
TI  - 300 pediatric renal transplantations: A single-center experience.
AB  - Our objective was to relate the results of 300 consecutive kidney transplants
      performed in children at a single center. PATIENTS AND METHODS: An analysis of
      kidney transplants was performed on patients less than 18 years old engrafted
      from May 1977 to August 2005. RESULTS: Among 300 kidney transplants, 48% of the
      patients were female, 87% were Caucasian, and 13% were African-Brazilian. The
      mean age at transplant was 11.5 +/- 4.5 years with 39 (13%) less than 6 years of
      age. The most frequent etiology of renal failure was vesicoureteral
      reflux/obstructive uropathy (36%) followed by glomerulopathy (27%). The donor was
      deceased in 32.3% and living related in 77.7% (parents 82%). The mean
      posttransplant follow-up was 4.8 +/- 4.3 years. The initial immunosuppression was
      CyA + AZA + PRED in 45%; CyA + MMF + PRED in 9.6%; TAC + AZA + PRED in 7.3%; TAC
      + MF + PRED in 9.7%; or TAC + MF without PRED in 10%. Sirolimus was employed
      initially in three cases. Induction with OKT3/ATG occurred in three patients and
      112 received an anti-IL2 receptor antibody. The 103 graft losses during 28 years
      of follow-up were secondary to chronic allograft nephropathy in 51 (49.5%),
      vascular thrombosis in 5 (4.8%), acute rejection in 12 (11.6%), and recurrence of
      original disease in 13 (12.6%). Sixteen (15.5%) died with functioning grafts.
      Graft survival in the first, fifth, and tenth year were 90%, 72%, and 59%,
      respectively. Patient survival in the first, fifth, and tenth years were 95%,
      93%, and 85%, respectively, with infection as the main cause of death.

PMID- 17175302
TI  - Differential pharmacokinetic interaction of tacrolimus and cyclosporine on
      everolimus.
AB  - OBJECTIVE: We characterized the pharmacokinetics of tacrolimus and everolimus in
      a combined immunosuppressive regimen. METHODS: This was an open-label exploratory
      trial in eight maintenance renal transplant patients with calcineurin inhibitor
      intolerance initially receiving mycophenolate mofetil (MMF) and tacrolimus. At
      enrollment, MMF was discontinued and replaced with everolimus 1.5 mg twice a day
      in study period 1 (days 1 to 10). In period 2 (day 11 to month 3), tacrolimus
      dose was reduced by half. RESULTS: At study entry tacrolimus trough level (C0)
      was 7.9 +/- 3.9 ng/mL and area under the curve over a dosing interval (AUC) was
      132 +/- 56 ng x h/mL. The addition of everolimus in period 1 did not change
      tacrolimus exposure: C0 8.4 +/- 4.0 ng/mL, AUC 134 +/- 70 ng x h/mL. Everolimus
      pharmacokinetics in the presence of tacrolimus in period 1 were: C0 3.3 +/- 1.2
      ng/mL, Cmax 10.4 +/- 5.1 ng/mL, AUC 58 +/- 20 ng x h/mL. When compared to
      pharmacokinetic data from a previous study in 47 renal transplant patients
      receiving everolimus at the same fixed dose (1.5 mg twice a day) with
      cyclosporine, everolimus exposure was 2.5-fold higher with cyclosporine relative
      to the data in this study with tacrolimus. After tacrolimus dose reduction in
      period 2, there was no clinically relevant change in everolimus exposure: C0 3.0
      +/- 1.1 ng/mL, Cmax 8.2 +/- 1.3 ng/mL, AUC 49 +/- 10 ng x h/mL. CONCLUSIONS:
      Tacrolimus appears to have a minimal effect on everolimus blood levels compared
      with the influence of cyclosporine. The dose of everolimus when combined with
      tacrolimus needs to be higher than when combined with cyclosporine in order to
      reach a given everolimus blood level.

PMID- 17175303
TI  - Rescue therapy by immunoadsorption in combination with tacrolimus and
      mycophenolate mofetil for C4d-positive acute humoral renal allograft rejection.
AB  - The aim of this study was to investigate the efficacy of immunoadsorption (IA) in
      combination with tacrolimus (TAC; 0.14 to 0.16 mg/kg/d) and mycophenolate mofetil
      (MMF; 1.5 to 2.0 g/d) rescue therapy for C4d-positive acute humoral rejection in
      nine cadaveric renal allograft recipients. Initial Panel reactive antibody (PRA-I
      and PRA-II levels were as high as 28.8% +/- 16.2% and 15.3% +/- 8.9%, IA therapy
      significantly decreased PRA-I and PRA-II levels to 5.9% +/- 2.9% and 2.2% +/-
      0.6%, respectively. Total serum immunoglobulin levels were markedly decreased.
      Repeated allograft renal biopsy in nine patients revealed remission of acute
      humoral rejection (AHR), and the deposition of C4d disappeared and reduced. With
      a mean follow-up of 29.4 +/- 5.4 months, patient and allograft survivals were
      100%, and renal function remained stable with a mean serum creatinine of 1.1 +/-
      0.3 mg/dL. Our findings suggested that a therapeutic approach combining IA and
      TAC and MMF rescue improved the outcomes of AHR.

PMID- 17175304
TI  - Calcineurin inhibitor avoidance versus steroid avoidance following kidney
      transplantation: Postoperative complications.
AB  - This study compared early postoperative complications in kidney transplant
      recipients treated with either a sirolimus-based calcineurin inhibitor (CNI)-free
      regimen or a tacrolimus-based steroid-free regimen. We used a single-center,
      prospective, sequential but nonrandomized study design. Consecutive recipients of
      primary cadaveric or non-HLA identical kidney transplant recipients received
      either a CNI-free regimen, consisting of sirolimus 5 mg daily beginning
      postoperative day 3, mycophenolate mofetil 1 gm twice a day, and
      methylprednisolone 500 mg intraoperatively, then prednisone 30 mg daily tapered
      to 10 mg daily at 3 months, or a prednisone-free regimen, consisting of
      methylprednisolone 500 mg, 250 mg, and 125 mg from days 0 to 2, then no further
      steroids, tacrolimus 0.075 mg/kg twice a day, and mycophenolate mofetil 1 g twice
      a day. All patients received thymoglobulin induction 6 mg/kg total dose. Outcome
      measures were patient and graft survival, BPAR, surgical and wound complications,
      viral infections and posttransplant diabetes mellitus (PTDM). Both groups had
      excellent early outcomes with no significant difference in patient or graft
      survival, early renal function, BPAR, surgical or wound complications, or viral
      infections between the two groups. Patients in the sirolimus-based CNI-free group
      had a significantly higher incidence of PTDM and a trend toward more
      discontinuation due to drug toxicity. Whether either regimen improves long-term
      outcomes awaits longer follow-up.

PMID- 17175305
TI  - Short-term results under three different immunosuppressive regimens at one
      center.
AB  - We examined short-term outcomes and posttransplant medical complications under
      three different immunosuppressive regimens at a single center. The study design
      was a randomized, prospective, open-label trial comparing a calcineurin inhibitor
      free (CNI) protocol to standard triple therapy with tacrolimus, prednisone, and
      mycophenolate mofetil. They were also compared to a concurrent but nonrandomized
      third cohort treated with a prednisone-free protocol. All three groups had
      excellent early outcomes with no significant difference in patient or graft
      survival or biopsy-proven acute rejection. Serum creatinine was significantly
      lower in the CNI-free recipients. Lipid panels and posttransplant diabetes
      mellitus were significantly lower in the prednisone-free patients. Prednisone
      free kidney transplant recipients have improved early glucose metabolism and
      hyperlipidemia compared to CNI-free or standard triple therapy recipients with
      comparable rejection and graft survival rates.

PMID- 17175307
TI  - Sirolimus attenuates the rate of progression of early chronic allograft
      nephropathy.
AB  - Optimal treatment for patients with chronic allograft nephropathy (CAN) is not
      known. Early intervention is preferred. We examined the benefit of adding
      sirolimus (SRL; C(0) 5-12 ng/mL: HPLC) on the rate of progression of early CAN.
      We identified patients with biopsy-confirmed Banff grade 1 CAN. After biopsy,
      patients were switched to SRL + CsA + prednisolone (SRL), MMF + CsA +
      prednisolone (MMF), or CsA + AZA + prednisolone (AZA). GFR was estimated by
      Cockcroft-Gault and MDRD formulae. The rate of GFR decline (delta GFR) was
      determined by calculating the slope of the regression line of estimated GFR (MDRD
      and Cockcroft-Gault method) at different times. Statistical analysis was
      performed by the Wilcoxon test. The 41 patients with CAN grade 1 were assigned to
      SRL: MMF: AZA = 12: 20: 9. Before biopsy; the graft age for SRL: MMF: AZA were 56
      +/- 27: 70 +/- 48: 51 +/- 36 months; and the GFR (MDRD method), 38 +/- 8: 42 +/-
      15: 36 +/- 14 mL/min; GFR (C-G method) 45 +/- 13, 42 +/- 12, 41 +/- 15 mL/min;
      trough CsA levels 152 +/- 36: 145 +/- 46: 177 +/- 61 ng/dL; delta GFR (MDRD
      method) -0.18 +/- 0.20: -0.15 +/- 0.59: -0.20 +/- 1.08; delta GFR (C-G method) 
      0.13 +/- 0.37: -0.19 +/- 0.24: -0.65 +/- 0.99. Follow-up time for SRL: MMF: AZA
      was 19 +/- 4: 35 +/- 32: 59 +/- 54 months. At last follow-up; GFR (MDRD method)
      for SRL: MMF: AZA were 39 +/- 13: 35 +/- 21: 40 +/- 24 mL/min; GFR (C-G method)
      46 +/- 17, 37 +/- 18, 46 +/- 25 mL/min; BP 128 +/- 11/79 +/- 7: 131 +/- 22/80 +/-
      14: 132 +/- 20/82 +/- 11 mm Hg; and CsA level 52 +/- 25: 122 +/- 41: 155 +/- 49.
      After biopsy, statin was prescribed in nine SRL, 10 MMF, and three AZA. ACEI was
      prescribed in two SRL, three MMF, and two AZA. Compared with the prebiopsy
      values, the delta GFR (MDRD method) changed to -0.04 +/- 0.31 (SRL; P = .04), 
      0.17 +/- 0.40 (MMF; P = .60), and -0.97 +/- 1.52 (AZA: P = .16). Delta GFR (C-G
      method) was also significantly improved in the SRL group (-0.02 +/- 0.47; P =
      .05) but not in the MMF (-0.13 +/- 0.51; P = .53) or AZA (-0.54 +/- 1.78; P =
      .44). We concluded that patients with early CAN who are switched to SRL and low
      dose CsA have a significant attenuation of the rate of GFR declination when
      compared with patients who receive MMF or AZA addition.

PMID- 17175306
TI  - Results of a calcineurin-inhibitor-free immunosuppressive protocol in renal
      transplant recipients of expanded criteria deceased donors.
AB  - The increasing number of patients on waiting lists and the relatively stable
      organ procurement rate provide the groundwork for the use of expanded criteria
      deceased donors. While calcineurin-inhibitors (CNI) are excellent
      immunosuppressive drugs, their nephrotoxicity is largely responsible for the lack
      of improvement in long-term graft survival. The objective of this study was to
      analyze the results obtained with the use of a calcineurin inhibitor-free
      immunosuppressive protocol (polyclonal antibody induction, plus sirolimus,
      mycophenolate mofetil, and low doses of steroids) in terms of graft and patient
      survival as well as posttransplant clinical complications over 2 years. Under
      this immunosuppressive protocol, 78.04% of the patients completed the follow-up.
      A protocol biopsy was performed on 17 patients (53.1%) within 2 years
      posttransplant of which 82.31% were diagnosed as chronic allograph nephropathy
      grade I. The incidence of clinical complications was low and not significantly
      different from that reported with other immunosuppressive schemes. Death-censored
      graft survival was 95.12%. In conclusion, the use of a calcineurin inhibitor-free
      protocol in renal-transplant recipients of expanded criteria deceased donors was
      associated with excellent graft and patient survival rates and a low incidence of
      adverse events.

PMID- 17175308
TI  - Proteinuria after conversion to sirolimus in renal transplant recipients.
AB  - Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently,
      proteinuria has been reported as a consequence of sirolimus therapy, although the
      mechanism has remained unclear. We retrospectively examined the records of 25
      renal transplant patients, who developed or displayed increased proteinuria after
      SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as
      conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia
      (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal
      cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78
      +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy
      was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d
      before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before
      conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients
      had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it
      increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight
      percent of patients showed increased proteinuria to the nephrotic range. Biopsies
      performed in five patients revealed new pathological changes: One
      membranoproliferative glomerulopathy and interstitial nephritis. These patients
      showed persistently good graft function. Serum creatinine values did not change
      significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at
      last follow-up (P = .14). Five grafts were lost and the patients returned to
      dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein
      of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3
      to 12) g/d after conversion (P = .01). Mean serum creatinine level before
      conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria
      was common after the use of SRL as rescue therapy for renal transplantation.
      Therefore, conversion should be considered for patients who have not developed
      advanced CAN and proteinuria. The possibility of de novo glomerular pathology
      under SRL treatment requires further investigation by renal biopsy.

PMID- 17175309
TI  - Post-rapamycin proteinuria: incidence, evolution, and therapeutic handling at a
      single center.
AB  - We performed a retrospective study to evaluate the safety, incidence, and
      management of proteinuria in 31 renal transplant recipients converted to
      Rapamycin (RAPA). All patients received RAPA immediately after the cessation of
      the calcineurin inhibitor or the antiproliferative drug. No acute rejection
      episodes were seen after this regimen. Chronic allograft nephropathy (58.1%) and
      calcineurin inhibitor toxicity (51.6%), both biopsy-proven, were the major
      reasons to introduce RAPA. Post-RAPA proteinuria was defined as the appearance of
      urine protein excretion >300 mg/d or any further increase in protein among those
      who showed previously elevated levels. We observed an elevated incidence of
      proteinuria of 48.4%. It started at 5.3 +/- 2.5 months after the conversion and
      60% occurred within 6 months. The proteinuria increased from a median of 200 mg/d
      to 1466 mg/d (P < .001). Age, gender, race, HLA mismatches, time to onset of
      RAPA, level of previous proteinuria, glomerular filtration rate, use of renin
      angiotensin blockers, and etiology of chronic kidney disease were similar between
      the groups with or without proteinuria. Once it appeared, we suspended the drug
      in only 4 patients (26.7%), initiated or augmented the dosage of renin
      angiotensin blockers in 26.7%, adjusted the RAPA dose in 20.1%, and did not
      perform a specific measure in 40% (6 of 15). At 15.6 +/- 12.7 months, 91% showed
      no further increase or reduction in proteinuria. We observed a high prevalence of
      proteinuria among renal transplant recipients converted to RAPA (48.4%). In
      addition, RAPA was suspended in only 4 patients and the proteinuria showed a
      tendency to stabilize or reduce over time.

PMID- 17175310
TI  - Exposure-efficacy relationships of a fingolimod-everolimus regimen in kidney
      transplant patients at risk for delayed graft function.
AB  - OBJECTIVE: We explored relationships between blood levels of fingolimod (FTY720)
      and everolimus versus treated biopsy-proven acute rejection (BPAR) in an open
      label trial in de novo kidney transplant recipients. METHODS: Patients (n = 52)
      who fulfilled predefined criteria placing them at increased risk of delayed graft
      function received fingolimod 2.5 mg/d, everolimus 2 mg twice daily with trough
      blood levels (C0) adjusted to 4 to 8 ng/mL, and corticosteroids. Everolimus and
      fingolimod C0 were collected over 1 year; efficacy readout was at 3 months.
      RESULTS: Fingolimod C0 accumulated over the first 3 months with a time-averaged
      level (C0avg) of 5.7 +/- 3.5 ng/mL. At steady state in months 3 to 12, C0 was 7.0
      +/- 4.4 ng/mL. Overall, 30 patients (58%) were free from BPAR to month 3.
      Patients were divided into four groups based on whether their fingolimod C0avg
      and everolimus C0avg were above or below the population medians. Freedom from
      BPAR was 53% and 57% for low fingolimod combined with low and high everolimus,
      whereas the percentages were improved to 83% and 85% for high fingolimod combined
      with low and high everolimus. CONCLUSIONS: This pilot study with an everolimus
      fingolimod regimen demonstrated trends in freedom from rejection that were drug
      concentration-related and that underscored, in particular, a strong contribution
      to efficacy from fingolimod.

PMID- 17175311
TI  - Immunoglobulin induction therapy in renal transplant recipients: Effects on
      immunoglobulin and regulatory antibody levels.
AB  - We have previously shown that high pretransplant regulatory autoantibodies are
      associated with better kidney graft outcome. To analyze the effect of intravenous
      immunoglobulin (IVIG) induction therapy on these regulatory antibodies, we
      performed a prospective randomized study in 50 renal transplant recipients who
      were randomly assigned to receive 7 x 10 g IVIG or 7 x 10 g IV albumin infusions.
      Basic immunosuppressive therapy consisted of tacrolimus/azathioprine (n = 24) and
      tacrolimus/mycophenolate mofetil (n = 26), respectively. ELISA was used to assess
      IgG-/IgA-anti-Fab, -anti-F(ab)2 and -anti-hinge regulatory antibodies. IVIG
      induction therapy resulted in upregulation of serum IgG and IgA levels within the
      first 20 days posttransplant (P = .001, IgG; P = .04, IgA), so that a significant
      IgG deficiency was found only in non-IVIG patients (day 10: IgG <6 g/L: 7/25
      (28%) non-IVIG versus 0/25 IVIG patients; P = .005). As the IVIG charges
      contained all of the regulatory antibodies tested, intravenous administration of
      these antibodies explain the elevated IgG- and IgA-anti-F(ab)2 antibody levels
      found in IVIG compared to non-IVIG patients on day 10 (P = .005 and P = .04,
      respectively). Our data indicated that IVIG induction prevented severe IgG
      deficiency in the early posttransplant period but had no impact on severe
      infectious complications. IVIG induction enhanced immunoregulatory antibody
      levels early posttransplant, which might provide graft protective effects.

PMID- 17175312
TI  - Podocin-related mechanisms in posttransplant [corrected] recurrence of focal
      segmental glomerulosclerosis [corrected].
AB  - Posttransplantation recurrence of focal segmental glomerulosclerosis (FSGS) is
      one of the most disarming events in human pathology with important social and
      psychological consequences. It usually occurs in 30% to 50% of patients affected
      by the primary form of the disease with an abrupt onset in the majority of cases
      occurring within 1 month of the transplantation. Prediction of recurrent cases
      and early therapy with plasmapheresis are the main goals of the therapy. Although
      the mechanism of posttransplantation recurrence is still obscure, it has been
      proposed to be of a multifactorial origin, in which plasma factors determine the
      shedding of proteins of the slit-diaphragm, such as nephrin and podocin, with
      structural alterations of the ultra-filtering unit of the glomerulus. Low
      resynthesis of podocin and/or haplo-insufficiency due to heterozygous mutations
      should represent significant predisposing factors to proteinuria. In this review,
      the role of podocin in posttransplantation recurrence will be evaluated focusing
      on the possibility that resynthesis of the protein could represent a key step
      also for stable normalization of the renal filter. The recent characterization of
      the podocin promoter cis- and trans- acting elements and the possibility to
      characterize low- and high-podocin producer haplotypes offer opportunities to
      evaluate the capacity for podocin resynthesis in the donor kidney. A review of
      the literature on posttransplantation recurrence of FSGS in patients originally
      carrying homozygous and/or heterozygous NPHS2 mutations supports the general idea
      of a multifactorial origin of the primary disease that can be extended to the
      pathogenesis of posttransplantation recurrence.

PMID- 17175313
TI  - Initial response to immunosuppressive and renoprotective treatment in
      posttransplant glomerulonephritis.
AB  - The current studies on posttransplant glomerulonephritis (PTxGN) do not establish
      when, how, or how long we must treat these patients. This study sought to compare
      the initial response to immunosuppressive treatment and renoprotection in PTxGN.
      PATIENTS AND METHODS: This prospective study was performed in 23 patients with a
      histological diagnosis of PTxGN. RESULTS: Mean follow-up was 12 months (3-18);
      91% received immunosuppressants, and 56.5% just renoprotective drugs. The best
      results (reduction of serum creatinine [SCr] and proteinuria) with
      immunosuppression were observed in patients with recurrent membranous PTxGN using
      the scheme of Ponticelli (IV + PO corticosteroid [CS] + PO cyclophosphamide
      [CPP]). A similar response was also seen in subjects with recurrent or de novo
      focal glomerulosclerosis treated with PO CS or CPP, except when the initial SCr >
      2.5 mg/dL. In de novo IgA nephropathy, reduction of proteinuria occurred with use
      of PO CS, with or without CPP, but without improvement in SCr. Patients with
      recurrent or de novo crescentic PTxGN used renoprotective drugs and always
      immunosuppressants. In this group, good results were seen with IV + PO CS, with
      or without CPP, when there was less than 50% of glomeruli with crescents, or more
      than 50% with crescents but an initial SCr < 2.5 mg/dL. CONCLUSION:
      Immunosuppression seemed to give a better initial response than renoprotection in
      cases of membranous, IgA, and focal segmental glomulerulosclerosis PTxGN.
      Patients with an initial SCr > or = 2.5 mg/dL displayed worse outcomes.

PMID- 17175314
TI  - Prevention of interstitial fibrosis of renal allograft by angiotensin II
      blockade.
AB  - We previously confirmed that losartan (LOS), an angiotensin-II (A-II) receptor
      blocker, diminished plasminogen activator inhibitor-1 (PAI-1) in cyclosporine
      (CsA)-treated renal graft recipients. Because PAI-1 is known to correlate with
      tissue fibrosis, we speculated that LOS would have the potential to prevent renal
      graft interstitial fibrosis. In this study, we focused our attention on the LOS
      induced histopathologic changes in renal grafts. Out of 24 CsA-treated
      normotensive kidney transplanted patients, 8 began to take 25 to 50 mg/day of LOS
      soon after kidney transplantation (group 1). Eight did so 2 years after kidney
      transplantation (group 2). Eight received no ARBs as a control group (group 3).
      PAI-1 levels were monitored every 3 months for 2 years. Renal graft biopsy was
      performed on all participants, with informed consent, before and 2 years after
      the onset of this study. The biopsy specimens were stained with periodic acid
      methenamine-silver (PAM)-Masson stain for light-microscopic examination. Fibrotic
      areas in each biopsy specimen were measured using the LUZEX-III image analyzing
      system. Statistical analysis was performed using Student's t-test. When we
      considered the pre-value of PAI-1 in each patient as 100%, the mean percent value
      of PAI-1 at 2 years after the onset of this study of groups 1, 2, and 3 were 81.5
      +/- 10.3%, 90.1 +/- 12.5%, and 116.8 +/- 11.9%, respectively (P < .01 groups 1
      and 2 vs group 3). Light-microscopic examination revealed less remarkable renal
      interstitial fibrosis among LOS administered groups. A-II blockade may be a key
      to prevent renal graft interstitial fibrosis.

PMID- 17175315
TI  - Utilization of vero cells for primary and chronic BK virus infection.
AB  - BK virus (BKV) nephropathy has a poor prognosis for renal allograft survival with
      30% to 60% risk of allograft loss over 1 year. In the past decade, BKV
      nephropathy has occurred in 1% to 10% of renal transplant patients, with higher
      rates observed in patients with increased immunosuppression exposure and renal
      allograft injury. Vero cells (Green monkey kidney cell origin) were optimized for
      BKV primary and chronic infection inclusive of culture requirements for 60-day
      growth and monolayer confluence. Quantification of BKV replication in the culture
      supernatant (SN) and cells was by real-time polymerase-chain reaction (PCR) using
      the Roche Lightcycler 2.0. Primary BKV infection of Vero cells is achieved by 2
      hour incubation with 6.5 x 10(5) BKV copies with subsequent washing of cells
      leading to steady-state cellular infection of 10(2) to 10(3) BKV copies. Primary
      infection is demonstrated within 7 to 10 days by a >10-fold increase of BKV
      copies in SN. Thereafter, a BKV viral load reduction in SN to a chronic/latent
      level (<10(2) BKV copies in SN) is observed by 14 days. Vero cells with chronic
      low-level BKV infection (10(2)-10(3) BKV copies in cells) exhibited reactivation
      (>10(5) BKV copies in SN) in >72% of late culture wells after 40 days. Vero cells
      can accommodate primary and chronic BKV infection followed by viral reactivation
      in late culture. The performance characteristics of 3 different pathogenic BKV
      strains obtained from patients with BKV nephropathy had infectivity profiles that
      correlated well the relative clinical profile in this Vero cell culture system.

PMID- 17175316
TI  - Cytomegalovirus infection in kidney transplant recipients: Evolution of approach
      through three eras.
AB  - Cytomegalovirus (CMV) prophylaxis is recommended for high-risk patients, while
      preemptive therapy is considered acceptable for patients at moderate/low risk.
      After reviewing kidney transplant patients from 1992-1995 and 1996-1999, we
      decided to replace prophylaxis by preemptive therapy. Herein we have presented
      our data. From 1996-1999 we treated 129 patients with ganciclovir prophylaxis for
      3 months if D+/R- or if they received depleting antibodies. The incidence of CMV
      was 13.2% versus 3.7% in the 1992-1995 cohort. The increase was associated with
      mycophenolate mofetil (MMF) use (P = .002). Forty-two percent of the D+/R-
      developed an infection with 89% of bouts occurring in the first month after
      cessation of prophylaxis. From 2002-2004, we never gave prophylaxis to 129
      patients except when they received thymoglobulin. High-risk D+/R- patients were
      monitored by polymerase chain reaction (PCR) CMV for 3 months. The incidence of
      CMV was 17.1% with 54% of the D+/R- developing CMV. CMV infection occurred mostly
      during the first trimester posttransplantation. Creatinine at 1 year
      posttransplantation was worse in the presence of CMV infection (154.3 mumol/L
      1.75 mg % versus 130.2 mumol/L-1.47 mg %, P = .03). Time to cure CMV infection
      was longer when MMF was discontinued: 36.7 days versus 69.9 days (P = .026). Our
      results indicated that CMV incidence is increasing: 3.7% (1992-1995) --> 13.2%
      (1996-1999) -->17.1% (2002-2004) and that it impairs 1 year graft function.
      Recovery was faster among patients still receiving MMF compared with those
      discontinuing MMF. Although MMF inhibits synthesis of anti-CMV IgM, it increases
      the anti-herpes virus effect of ganciclovir and may protect against chronic
      allograft nephropathy. Based on our experience, we plan to reintroduce
      prophylaxis in high-risk patients and to continue MMF when treating CMV
      infection.

PMID- 17175317
TI  - Possible relations between thyroid function, endothelium, and kidney and liver
      function in kidney allograft recipients.
AB  - BACKGROUND: Renal function affects the thyroid gland in many ways. Disturbances
      in hemostasis and endothelial damage are common complications of kidney disease.
      Endothelial dysfunction may link these two processes. AIM AND METHODS: This cross
      sectional study examined thyroid hormones in relation to markers of endothelial
      damage and inflammation among 80 kidney allograft recipients and 29 healthy
      volunteers. Thyroid hormones, markers of endothelial damage (vWF, thrombomodulin,
      intracellular adhesion molecule [ICAM] vascular adhesion molecule [VCAM], CD146),
      markers of inflammation (hsCRP), other hemostatic parameters (thrombin
      antithrombin complexes [TAT], prothrombin fragments 1 + 2 [F1 + 2], plasmin
      antiplasmin complexes, tissue plasminogen activator and its inhibitor, platelet
      glycoprotein [V-GPV]) as well as P-selectin were measured using commercially
      available kits. RESULTS: Total T3 was significantly lower among kidney allograft
      recipients, whereas markers of endothelial dysfunction and inflammation were
      significantly elevated over controls. In kidney allograft recipients total T3 was
      independently related to PAI-1, ICAM, and eGFR, whereas free T3 was independently
      related to thrombomodulin, aspartate, and alanine aminotransferases, hemoglobin,
      urea, eGFR, dose of cyclosporine and treatment with mycophenolate
      mofetil/azathioprine. Total T4 was related to aspartate and alanine
      aminotransferases, dose of cyclosporine, PAI-1, and ICAM. In multiple regression
      analysis the only correlates of T3 were PAI-1 and ICAM, whereas the only
      correlates of free T3 were thrombomodulin, aspartate aminotransferase, eGFR, and
      cyclosporine dose. In healthy volunteers GPV was related only to TSH.
      CONCLUSIONS: We described novel relations between thyroid hormones and markers of
      endothelial dysfunction in kidney transplant recipients. In kidney transplant
      recipients thyroid function metrics were associated with endothelial damage,
      immunosuppressive treatment, liver and kidney function. Therefore, the relations
      between thyroid axis and endothelium in kidney allograft recipients merit
      additional studies.

PMID- 17175318
TI  - Hypercalcemia due to resistant hyperparathyroidism in renal transplant patients
      treated with the calcimimetic agent cinacalcet.
AB  - INTRODUCTION AND AIMS: Calcimimetic agents increase the sensitivity of calcium
      sensing receptors of parathyroid glands and suppress both serum calcium levels
      and parathyroid hormone (PTH). The use of these drugs in patients with a
      functioning graft suffering from resistant hyperparathyroidism and hypercalcemia
      is still under investigation. We report seven patients who were treated with the
      calcimimetic agent cinacalcet. METHODS: The four male and three female patients
      of 38 to 72 years of age received a renal transplant from 4 to 35 months before
      cinacalcet treatment. Serum creatinine was 1.2 to 1.8 mg/dL (estimated glomerular
      filtration rate between 40 and 75 mL/min). Immunosuppressive treatment consisted
      of interleukin-2 antibody induction therapy, calcineurin inhibitors (cyclosporine
      or tacrolimus), prednisolone, and mycophenolate mofetil. Mild to severe
      hyperparathyroidism resistant to vitamin D analog treatment (intact parathyroid
      hormone molecule [iPTH] 174 to 519 pg/mL) was accompanied by severe hypercalcemia
      (Ca >11 mg%). To date the patients have completed 3 to 18 months of therapy.
      Cinacalcet 30 mg/d was initially administered. RESULTS: This treatment resulted
      in a rapid decrease in total serum calcium (8.6 to 9.2 mg/dL) while PTH showed a
      milder, progressive decrease. Having controlled calcium levels, 1alpha OH vitamin
      D (0.25 microg/d per os) was added to the treatment, which resulted in a further
      decline of iPTH without producing an increase in serum calcium concentrations
      (median initial iPTH value 401 pg/mL, median value after treatment 176 pg/mL).
      Therapy was well tolerated without hypocalcemic events. CONCLUSION: Cinacalcet
      offered a better holistic treatment approach to such patients.

PMID- 17175319
TI  - The evolution of weight and body composition in renal transplant recipients: Two
      year longitudinal study.
AB  - Previous series have reported weight gain after kidney transplantation. However
      few studies have investigated the body composition after kidney transplantation,
      particularly during longitudinal follow-up. In this prospective study, we
      assessed the changes in body composition after kidney transplantation. We also
      analyzed the effect of steroid withdrawal from the immunosuppressive regimen on
      weight gain and body composition. METHODS: Thirty-eight cadaveric kidney
      transplant recipients were followed for 2 years posttransplant. Total and
      segmental body composition were measured by dual energy X-ray absorptiometry
      (DEXA) at the time of transplantation as well as 3, 6, 12, and 24 months later.
      RESULTS: In 28 patients (group A), prednisone was stopped by month 6, whereas, in
      10 patients (group B), it was continued throughout the study. In the overall
      patient group, there were no significant changes in body weight. However, a trend
      to increased weight was observed in group B. In this group, patients showed an
      early increase in total body fat with a central accumulation of fat mass that was
      maintained during the follow-up period. On the other hand, total lean mass
      increased significantly in group A but did not change significantly in group B.
      CONCLUSION: In summary, overall the group showed no major changes in body weight
      during the 2 years after transplantation. Steroid withdrawal in kidney transplant
      recipients may have a significant positive effect on body composition.

PMID- 17175320
TI  - Risk factors for wound healing complications in sirolimus-treated renal
      transplant recipients.
AB  - Impaired surgical site healing occurs in 20% to 50% of sirolimus (SRL)-treated
      renal transplant (RT) recipients, with most patients having received concomitant
      corticosteroids. We determined the incidence of surgical site complications among
      RT recipients receiving SRL with mycophenolate mofetil (MMF), with most patients
      on a steroid-avoidance protocol. SRL/MMF patients with complications within 3
      months of transplantation were compared with 1) SRL/MMF patients without them and
      2) matched RT recipients receiving tacrolimus (FK)/MMF. Between January 2002 and
      March 2005, 44 of 300 (15%) RT recipients received SRL within 6 weeks of
      transplantation. Fourteen (31.8%) developed lymphocele, bladder leak, wound
      dehiscence, cellulitis, or an abscess. Obesity (BMI > or =30 kg/m2) was
      significantly associated with problems: the mean BMI of SRL cases with
      complications was 29.9 kg/m2 vs 25.4 kg/m2 for SRL patients without them (P =
      .047). Seventy-one percent of obese SRL patients experienced complications
      compared with 24.3% (P = .025) of non-obese SRL patients. Surgical treatment was
      required in 29% of patients. Rates of maintenance steroid use were similar in SRL
      complicated cases compared with SRL patients without them. The FK control group
      showed a lower rate of complications (14.3%; P = .163) despite similar BMI,
      rejection rates, and chronic steroid use as the SRL group. Obesity and graft
      rejection were independent predictors of complications. Thus, among a group of
      predominantly steroid-free recipients on SRL, the rates of wound complications
      were similar to those seen previously, but the highest risk for them was observed
      in obese recipients and in those with acute rejection episodes. Wound
      complications were associated with significant morbidity.

PMID- 17175321
TI  - Does opening the peritoneum at the time of renal transplanation prevent
      lymphocele formation?
AB  - BACKGROUND: The occurrence of lymphocele formation following renal
      transplantation is variable, and the optimal approach to treatment remains
      undefined. Opening the peritoneum at the time of transplantation is one method of
      decreasing the incidence of lymphocele formation. The purpose of this study was
      to determine whether creating a peritoneal window at the time of transplantation
      decreases the incidence of lymphocele formation. METHODS: We performed a
      retrospective review of renal transplants conducted at our institution between
      2002 and 2004. Records were reviewed to obtain details regarding opening of the
      peritoneum at the time of transplant and occurrence of lymphocele. Every patient
      underwent routine ultrasound imaging in the peri-operative period. Graft
      dysfunction secondary to the lymphocele was the primary indication for
      intervention. Data were analyzed by chi-square. RESULTS: During the initial
      transplant the peritoneum was opened in 35% of patients. The overall incidence of
      fluid collections, identified by ultrasound, was 24%. Opening the peritoneum did
      not decrease the incidence of lymphocele. However, more patients with a closed
      peritoneum required an intervention for a symptomatic lymphocele. In the 11
      patients with an open peritoneum and a fluid collection, only one required an
      intervention. In patients whose peritoneum was left intact, 24% of fluid
      collections required intervention. Graft survival was equivalent. CONCLUSION:
      Creating a peritoneal window at the time of transplantation did not decrease the
      overall incidence of postoperative fluid collections. However, forming a
      peritoneal window at the time of transplantation did decrease the incidence of
      symptomatic lymphocele.

PMID- 17175322
TI  - Cardiac functional and morphologic changes of renal allograft recipients in the
      early posttransplant period.
AB  - After renal transplantation there is a substantial alteration in cardiac
      morphology and functions. This prospective study was undertaken to observe
      changes in different cardiac parameters in early months after transplantation.
      PATIENTS AND METHODS: Twenty-two allograft recipients (primary disease
      glomerulonephritis) were evaluated in the immediate pretransplant period (0
      month) and 1 and 3 months after transplantation by clinical and echocardiographic
      (M mode, 2D) evaluations. RESULTS: Pretransplant echocardiogram showed left
      ventricular hypertrophy (LVH) in 100% subjects, LV dilation in 52%, and systolic
      dysfunction in 18%. By the third month, significant differences in systolic blood
      pressure (SBP-161 +/- 16 to 133 +/- 26 mm Hg, P < .002); diastolic BP (DBP-101 +/
      9 to 86 +/- 11 mm Hg, P < .006), and hemoglobin level (Hgb-7.3 +/- 1.6 to 11.2
      +/- 3.9 g/dL, P < .006) were evident. Echocardiography showed decreased left
      atrial diameter (LADd-41 +/- 5 to 35 +/- 3 mm, P < .001); left ventricular
      internal diameter (LVIDd-54 +/- 6 to 47 +/- 6 mm, P < .02); left ventricular
      muscle mass index (LVMI-379 +/- 114 to 248 +/- 58 g/m(2), P < .001); and left
      ventricular end diastolic volume index (LVEDVI-96 +/- 28 to 64 +/- 17 ml/m2, P <
      .002). Bivariate correlations showed positive associations of mean blood pressure
      (MBP) and serum creatinine with LVMI, LVEDVI, and negative association of
      hemoglobin with MBP, serum creatinine, LVMI, and LVEDVI. CONCLUSION: From these
      observations, we concluded that cardiac morphological parameters start improving
      in the early posttransplant period. Improvements in renal function, anemia
      status, and lower blood pressure showed strong associations with these changes.

PMID- 17175323
TI  - Posttransplant diabetes mellitus in renal allograft recipients: A prospective
      multicenter study at 2 years.
AB  - The purpose of this study was to investigate the incidence and risk factors for
      the development of diabetes mellitus after kidney transplantation (PTDM). A total
      of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to
      December 2002 were included. Diabetes was diagnosed following American Diabetes
      Association criteria. While 1276 patients were treated with tacrolimus (Tac),
      mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME
      (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%,
      12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was
      21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at
      24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months
      (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was
      similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac
      MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%)
      and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P < .05). By
      Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P <
      .001), body mass index (BMI) > 30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27
      2.16; P < .001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P =
      .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24
      months in immunosuppressive protocols including MMF is about 22%, and it is
      associated with older age, increased BMI, and immnunosuppression with Tac.

PMID- 17175324
TI  - Immunosuppression and cancer: A comparison of risks in recipients of organ
      transplants and in HIV-positive individuals.
AB  - The comparison of cancers occurring excessively among HIV-infected and
      transplanted individuals may help to elucidate the relationship between immune
      surveillance, viral infections, and cancer. A longitudinal study was conducted on
      2002 HIV-infected Italian subjects, 6072 HIV-infected French individuals, and
      2878 Italian recipients of solid organ transplants. Standardized incidence ratios
      (SIR) and 95% confidence intervals (CI) were computed to quantify the risk for
      cancer, compared with the French and Italian general populations. The SIRs for
      all cancers were 9.8 (95% CI: 9.0-10.6) for HIV-infected individuals versus 2.2
      (95% CI: 1.9-2.5) for transplant recipients. In both groups, most of the excess
      risk was attributable to virus-related cancers, such as Kaposi's sarcoma (KS; SIR
      = 451 in HIV-positive individuals, 125 in transplant recipients), non-Hodgkin's
      lymphoma (NHL; SIR = 62.1 and 11.1, respectively), and liver cancer (SIR = 9.4
      and 4.1, respectively). Significantly increased SIRs for anal cancer and
      Hodgkin's lymphoma were found only among HIV-positive individuals. Among women
      younger than 40 years of age, a more than 10-fold increase in cervical cancer
      risk was found in both groups. Among HIV-infected individuals treatment with
      highly active antiretroviral therapies drastically reduced SIRs for KS and NHL
      only. These results show that HIV-infected individuals and transplant recipients
      share a similar pattern of cancer risk, largely due to virus-related cancers.

PMID- 17175325
TI  - Characteristics of neoplasm occurrence and the therapeutic effect of sirolimus in
      South Chinese kidney transplant recipients.
AB  - Kidney transplantation (KTx) recipients are at a higher risk of oncogenesis when
      compared to the general population. Sirolimus (SRL), a potent immunosuppressant,
      has shown promising antineoplastic effects in vitro and in vivo. This study
      retrospectively analyzed the neoplasm occurrence and the efficiency of SRL on
      unresectable malignancies in South Chinese KTx recipients. Thirty-three (1.64%)
      of 2017 patients who received KTx from January 1984 to December 2004 developed
      neoplasms at 4 to 117 months posttransplant, mostly in digestive organs (33.3%),
      the hematologic system (15.2%), or the skin (12.1%). The most common type was
      liver cancer (24.2%), followed by skin cancer, lymphoma, and thyroid cancer
      (9.1%). The median survival times were 41.5 and 6.0 months for those who did (n =
      10) receive radical surgery or did not (n = 23), respectively. The 20-month
      survival rates were 70.0% versus 13.0% (P < .01). For unresectable patients, the
      median survival time of those treated with SRL (n = 8) was 14.5 months compared
      to 3.0 months for those who did not (n = 15). The survival rates at 12(th) and
      20(th) months were 75.0% and 37.5% in the SRL group and 6.7% and 0% in the non
      SRL group (P < .05). In conclusion, when compared with Western studies, a lower
      incidence and unique location pattern (liver cancer-dominant) are characteristics
      of de novo posttransplant neoplasms in South Chinese KTx recipients. Early
      diagnosis and feasible radical surgery are favorable for prognosis, and SRL is a
      treatment of choice for KTx recipients with neoplasms.

PMID- 17175326
TI  - Albumin dialysis has no clear effect on cytokine levels in patients with life
      threatening liver insufficiency.
AB  - Cytokines play a important role in life-threatening liver insufficiency. They are
      released within the liver in response to hepatic injury and inflammation. To
      study cytokine clearance during albumin dialysis treatment (Molecular Adsorbent
      Recirculating System [MARS]), we monitored proinflammatory (tumor necrosis factor
      alpha [TNF-alpha] and interleukin-8 [IL-8]) and anti-inflammatory (IL-10 and IL
      6) cytokines and the lymphocyte activation marker IL-2sRalpha in 81 consecutive
      ICU patients displaying serious hepatic decompensation. Cytokine levels were
      measured before treatment and after the last MARS treatment in 49 acute liver
      failure (ALF) and 32 acute decompensation of chronic liver disease (AcOChr)
      patients who were mainly considered for liver transplantation. No significant
      change in cytokines was observed before versus after the last MARS treatment in
      the AcOChr group, and only IL-10 decreased significantly in the ALF group.
      Baseline levels of IL-8 and IL-6 were significantly lower and IL-10 was higher in
      the ALF group compared with those in the AcOChr group. TNF-alpha and IL-2sRalpha
      levels did not differ between the groups. After treatment, IL-8 was also
      significantly lower in ALF patients compared with the levels in AcOChr patients.
      In this study, MARS therapy did not show a clearly identifiable efficacy at
      removing circulating cytokines. However, the results revealed that ALF and AcOChr
      patients displayed different profiles of circulating cytokines.

PMID- 17175327
TI  - Molecular adsorbent recirculating system in liver transplantation: Safety and
      efficacy.
AB  - We assessed the safety and clinical efficacy of the Molecular Adsorbent
      Recirculating System (MARS) in liver failure patients admitted to our intensive
      care unit (ICU) from May 2000 to February 2006. Of 28 adult patients with
      bilirubin >15 mg/dL and hepatic encephalopathy (HE) grade > or =2 or hepato-renal
      syndrome, 22 patients were included in the study, because 6 patients were older
      than 65 years of age or showed recent alcohol abuse or extrahepatic malignancy.
      Patients were assigned to 2 groups according to whether MARS therapy was
      associated with a transplantation procedure: 11 patients received MARS therapy
      and liver transplantation (OLT group) and 11 patients received MARS therapy alone
      (non-OLT group). Five of 11 patients in the OLT group were listed for
      transplantation and 6 patients with graft failure for retransplantation. The
      patients in the OLT and non-OLT groups were similar in MELD, SOFA, and SAPS
      scores. All patients were stable and free from complications. MARS significantly
      reduced bilirubin, bile acids, and blood urea nitrogen (BUN) levels in both
      groups (P < .05), whereas a significant decrease in ammonia level was observed in
      the OLT group. Patient survival rates at 3 and 6 months in the OLT group were 91%
      and 73%, respectively, and in the non-OLT group, 9% and 9%, respectively (P <
      .001). MARS was safe and well tolerated, improving biochemical parameters,
      neurological function, and pruritus. In terms of survival, the use of MARS alone
      was not effective due to the high rate of multiple organ failure. Nevertheless,
      the association of MARS with a transplant/retransplantation procedure was highly
      effective.

PMID- 17175328
TI  - Analysis of hospitalizations comparing rifaximin versus lactulose in the
      management of hepatic encephalopathy.
AB  - INTRODUCTION: Patients with end-stage liver disease often develop hepatic
      encephalopathy. The loss in cognitive abilities results in marked economic loss
      to the patient and health care community. We report hospital admission rates and
      economic impact of patients with end-stage liver disease suffering from hepatic
      encephalopathy. METHODS: The medical records were reviewed involving liver
      transplant patients started on lactulose or rifaximin therapy after presenting
      with stage 2 hepatic encephalopathy from January 2004 to November 2005.
      Information collected included demographics, hospitalizations required for
      hepatic encephalopathy, economic data, and Model for End-stage Liver Disease
      (MELD) score. RESULTS: Thirty-nine patients met study criteria: 24 patients
      treated with lactulose (group one) and 15 with rifaximin (group two). Group one
      included 18 men and six women of mean age 48 (range 39 to 58), average MELD 14
      (range 10 to 19). Group two included 10 men and five women of mean age 47 (range
      42 to 58), average MELD 15 (range 10 to 19). Group one patients required 19
      hospitalizations overall: three patients with three hospitalizations, four
      patients with two hospitalizations, and two patients required one
      hospitalization. Total drug cost per month was 50 dollars(group one) and 620
      dollars(group two). The average annual cost of hospitalization, emergency room
      visit, and drug per patient treated was 13,284.96 dollars for a total of 318,839
      dollars (range 5005 dollars to 26,255 dollars, including drug cost and hospital
      care). Group two required three hospitalizations, all three with one visit. The
      average annual cost of hospitalization, emergency room visit, and drug per
      patient treated was 7958.13 dollars for a total of 119,372 dollars (range 6005
      dollars to 19,255 dollars, including drug cost and hospital care). The total cost
      of therapy per patient per year was 13,285 dollars (group one) versus 7958
      dollars (group two). The average length of stay was shorter in group two [3.5
      days (range 3 to 4)] versus group 1 [5.0 days (range 3 to 10); P < .0001].
      CONCLUSION: These pilot data demonstrate the marked difference in economic costs
      for the treatment of hepatic encephalopathy. The results also show that in
      comparative groups, the economic gains are quickly lost when using lactulose.

PMID- 17175329
TI  - Stem cell factor levels do increase in patients subsequent to hepatectomy with
      the extent of parenchymal loss.

PMID- 17175330
TI  - Neuropsychological changes in a large sample of liver transplant candidates.
AB  - One-hundred forty-eight pre-liver transplant candidates completed a psychological
      interview and brief neuropsychological testing. Assessment measures included the
      Repeatable Battery of Neuropsychological Status, Shipley Institute of Living
      Scale, Trail Making Test Parts A and B (TMT-A and TMT-B), and the Folstein Mini
      Mental State Exam. Participants in our sample scored in the Below Average range
      of functioning (mean score = 100; SD = 10) on measures of memory (mean = 89.51,
      SD = 17.43), attention (mean = 87.62, SD = 17.23), and spatial perception (mean =
      88.69, SD = 20.39). Scores reflected moderate to severe impairment in
      organization and processing speed (TMT-B completion time in seconds: mean =
      137.22, SD = 88.64). Controlling for the effects of prior education, MELD scores
      were strongly correlated with poorer performance on immediate and delayed memory
      subtests (both P < .01), as well as with diminished attentional capacity (P =
      .03). MELD scores also were significantly related to slower completion times on
      the TMT-A and TMT-B (both P < .05). Furthermore, independent sample t tests
      indicated that patients with higher MELD scores (>10) experienced significantly
      greater difficulty with executive functioning (P < .05) and delayed memory (P <
      .05) than those with lower MELD scores. Thorough evaluations of cognitive
      functioning are needed pretransplant to identify and treat cases of subclinical
      hepatic encephalopathy before daily functioning becomes significantly impaired.

PMID- 17175331
TI  - Cost analysis of tumor downsizing for hepatocellular carcinoma liver transplant
      candidates.
AB  - We report the results of a prospective, intent-to-treat (ITT) trial on the costs
      of selective tumor downsizing (DS) before liver transplantation (LT) for patients
      affected with hepatocellular carcinoma (HCC). The trial started in January 1997
      including adult patients with nodular-type HCC within and beyond the Milan
      criteria. Patients were downsized with transarterial chemoembolization (TACE),
      percutaneous ethanol injection (PEI) and/or radiofrequency ablation (RFA)
      according to clinical predictors. TACE and RFA were performed as inpatient
      procedures, while PEI was performed on an outpatient basis. Costs of DS were
      obtained according to the Tuscany Health Reimbursement Fee Catalog adjusted to
      yearly inflation rates from 1997 through 2005. Data analysis was performed at 1
      year after the last enrollment of 198 patients, including 161 (81.3%) who were
      transplanted: 34 (17.2%) dropped out and 3 (1.5%) were still on the waiting list.
      One hundred and fifty-two patients (76.7%) underwent DS for a total of 201
      procedures: 159 TACE, 39 PEI, and 3 RFA. Overall costs in Euros (euro) of
      waitlisting were 861,801.24 euro: 548,460 euro (63.7%) for pretransplantation
      evaluation; 197,994.84 euro (22.9%) for control visits and hospitalizations; and
      115.346.4 euro (13.4%) for DS. Mean costs of DS were 758.58 euro +/- 270 euro per
      downstaged patient (747.53 euro +/- 257.1 euro Milan; 774.01 euro +/- 287.71 euro
      non-Milan); 582.85 euro +/- 398.87 euro per waitlisted patient (520.28 euro +/-
      406.23 euro Milan; 520.28 +/- 364.48 euro non-Milan); and 716.4 euro per
      transplanted patient (580.67 euro Milan; 1026.76 euro non-Milan; +76.8%). A
      selective policy of tumor DS increased the costs of LT waitlisting by 13.4%, but
      due to higher dropout rates among non-Milan patients, the cost utility of DS was
      76.8% higher in the Milan group.

PMID- 17175332
TI  - Outcome of imported liver allografts and impact on patient access to liver
      transplantation.
AB  - Liver allografts declined by local transplant centers are then offered regionally
      or nationally as imported grafts. Most of these grafts are declined because of
      poor donor quality. We retrospectively reviewed the medical records of patients
      who underwent liver transplantation between January 2004 and December 2005. There
      were 102 liver transplants in 98 recipients. They were divided into two groups:
      imported graft recipients (n = 37) and locally procured grafts recipients (n =
      61). Eighty-six percent (32 of 37) of imported grafts were obtained from extended
      criteria donors defined as subjects treated with high doses of ionotropes with
      elevated liver enzymes, donor age over 70 years, macrosteatosis above 25%,
      positive hepatitis C or hepatitis B core antibody serology, systemic disease,
      history of cancer, hypernatremia, or with infection. The remaining grafts were
      declined due to unavailability of suitable recipients or social history.
      Recipient age and etiology of liver disease were similar for both groups. The
      mean MELD score was 22.1 +/- .9 among the imported graft recipients and 26.1 +/-
      1 for the locally procured graft recipients (P < .01). There was no difference in
      blood loss or postoperative complications. Postoperative mean peak total
      bilirubin was similar in both groups. However, imported graft recipients had
      significantly higher mean peak AST (2436 +/- 282 vs 1380 +/- 165 U/L, P < .001)
      and ALT (1098 +/- 114 vs 803 +/- 87 U/L, P < .05). Primary graft nonfunction as
      well as 30 day and 1-year patient and graft survivals were similar for both
      groups. In conclusion, imported grafts can be transplanted in selected patients
      with outcomes comparable to locally procured grafts.

PMID- 17175333
TI  - Allocation of nonstandard livers to transplant candidates with high MELD scores:
      Should this practice be continued?
AB  - MELD and PELD scores of 255 consecutive grafts were calculated (236 adult cases
      and 19 pediatric cases). No correction for the etiology of liver disease was
      performed. Retransplants were excluded. Three categories of patients were
      identified: low MELD (scores <12, n = 61); intermediate MELD (scores between 12
      24, n = 159); high MELD (scores > or =25, n = 35). Grafts were categorized
      according to donor quality: standard livers (n = 199), vs nonstandard livers (n =
      56). Nonstandard livers were identified by age > or =60, or at least by two of
      the following conditions: severe hemodynamic instability, ultrasound evidence of
      steatosis, natriemia > or =155 mEq/L, ICU stay >7 days, liver trauma, protracted
      anoxia as cause of brain death, transaminases levels x 4. In standard livers, the
      12-month graft survival (GS) for low, intermediate, and high MELD classes were
      88%, 74%, and 77%, respectively. In nonstandard livers, the 12-month GS for the
      low, intermediate, and high MELD classes were 84%, 55%, and 44%, respectively;
      differences between low MELD class and both intermediate and high MELD classes
      were significant (P < .05). Cox regression analysis of all cases identified the
      following parameters as independent predictors of GS: donor status; donor age;
      and recipient creatinine. The highest correlation with GS was found using donor
      age and recipient creatinine as covariates. In standard livers no variable was
      able to predict GS. In nonstandard livers the MELD-PELD score was the unique
      variable able to predict GS. We suggest avoiding the use of nonstandard livers
      for patients with high MELD scores.

PMID- 17175334
TI  - Comparison of histidine-tryptophan-ketoglutarate and University of Wisconsin in
      living-donor liver transplantation.
AB  - For cadaveric transplantations, histidine-tryptophan-ketoglutarate (HTK) and
      University of Wisconsin (UW) solutions have been shown to engender similar
      outcomes. In September 2004, our institution changed from UW to HTK as the
      primary preservation solution for liver and kidney transplantations. We reviewed
      records of living-donor liver transplant recipients from September 2001 to
      December 2005. This study compared early postoperative outcomes of liver
      transplantation using the 2 solutions. Perfusion was performed first via the
      portal vein and then via the hepatic artery until the outflow became clear.
      Patients were compared based on the organ preservation solution. The analysis
      included patient demographics, early postoperative complication rates, mortality
      rates, number of acute rejection episodes, costs for preservation solutions, and
      results of 1-, 7-, 14-, and 30- day liver function tests. Patients in both groups
      were managed with similar operative techniques, immunosuppressive regimens, and
      donor liver criteria. Statistical analyses were performed with chi- square and
      Mann-Whitney U tests. Donor and patient demographics were similar. No
      statistically significant differences were observed between the groups with
      regard to posttransplantation liver biochemistry, complication rates, number of
      acute rejection episodes, and mortality rates. The mean infused volume of
      preservation solution was 1000 +/- 400 mL (range, 500-2000 mL) for all patients.
      These volumes corresponded to a cost savings of US 148 dollars/L when using HTK
      solution. In conclusion, UW and HTK were equally effective and safe for perfusion
      of living-donor liver grafts; however, the use of HTK solution provided
      significant cost savings.

PMID- 17175335
TI  - Safety of multidetector computed tomography in calculating liver volume for
      living-donor liver transplantation.
AB  - Living-related liver transplantation was developed to overcome the organ shortage
      for both children and adults with end-stage liver disease. Because impaired liver
      function after resection and transplantation is caused by insufficient liver
      volume, the reliable volumetric assessment of the hepatic segments of potential
      living donors is a critical element in preoperative evaluation. In this study, we
      compared the results of multidetector computed tomographic (CT) volumetry with
      the intraoperative findings from 80 liver transplantations performed at our
      center. Resection borders were determined preoperatively with the aid of CT by
      manual delineation in which the hepatic vessels were used as guides. Resected
      liver grafts were weighed intraoperatively, and the calculation of their volume
      was based on the specific weight of 1 g/mL. Statistical analyses were performed
      with Pearson's correlation test; P < .05 was considered significant. The study
      subjects consisted of 48 women and 32 men (mean age, 35.6 +/- 9.7 years; range,
      23-56 years). Forty-one donors underwent right lobectomy, 22 underwent left
      lobectomy, and 17 underwent left lateral segmentectomy. Manual volumetric
      measurement was completed within 15 minutes. No significant differences were
      found between the results of preoperative volumetry and the intraoperative
      measurement. We therefore concluded that manual CT volumetric calculation is a
      reliable method of calculating liver volume for living-donor liver
      transplantation.

PMID- 17175336
TI  - Hypercoagulability risks among adult living liver donors.
AB  - BACKGROUND: Review of the literature is limited with respect to thrombotic risk
      in the living liver donor. This study examines inherent coagulable changes that
      occur as a result of the surgery. MATERIALS AND METHODS: At our center, we have
      performed 353 orthotopic adult liver transplants in the past 4 years. Of these,
      20 were adult-adult right lobe living donor transplants. All living donors are
      alive and doing well. Of these, eight living donors were followed preoperatively
      and postoperatively monitoring protein C, protein S, antithrombin III, and factor
      VIII levels. Levels were checked at 48 hours postoperatively, as well as at 2, 4,
      and 6 weeks. RESULTS: All eight patients had normal levels preoperatively,
      although significantly low levels were identified postoperatively of these
      coagulation markers: protein C decreased to as low as 0%, (range 0-29; normal 50
      150) within 48 hours postoperatively; protein S decreased to 3% to 40% during the
      same time frame (normal 50-150), and antithrombin III levels decreased to 47% to
      55% (normal range 50-150%). Factor VIII levels significantly increased to >200%
      (normal 50- 150). All coagulation levels returned to the normal range within 4 to
      6 weeks. None of the patients developed a thromboembolic event. CONCLUSIONS: We
      observed an imbalance of low protein C, S, and antithrombin III and elevated
      factor VIII levels, which have been documented as thrombotic risks in adults. Our
      findings suggest that the imbalance in the coagulation profile after surgery may
      be an independent risk factor for thrombosis beyond the surgical event, a
      phenomenon that requires further exploration.

PMID- 17175337
TI  - Efficacy of right anterior sector drainage reconstruction in right-lobe live
      donor transplantation.
AB  - BACKGROUND: Without including the middle hepatic vein (MHV) into right-lobe
      grafts, venous drainage of the anterior segment (AS) has always been a concern.
      The efficacy and the necessity of additional venous reconstruction in the AS for
      graft viability and function are still controversial. METHODS: Since February
      2002, 57 right-lobe grafts were implanted into adult recipients. The mean graft
      to ideal recipient weight ratio (GRWR) was 1.3% (minimum: 0.8%, maximum 2.1%).
      All minor venous tributaries to the MHV less than 5 mm in diameter were ligated.
      The management of MHV tributaries was categorized into three groups: (A) no major
      tributaries (n = 33); (B) major tributaries ligated (n = 11); and (C) major
      tributaries reconstructed (n = 13). Reconstructions were established using
      vascular grafts (PTF, n = 8; cadaveric, n = 2) or joining with right hepatic vein
      orifice (n = 6). The groups were homogenous in age, gender, MELD (17 +/- 6, 16 +/
      4, 18 +/- 7), graft weight (817 +/- 181, 838 +/- 152, and 855 +/- 159 g), and
      graft/ideal liver weight ratio (0.54 +/- 0.12, 0.57 +/- 0.13, and 0.57 +/- 0.1,
      respectively). We investigated the volume of ascites, serum bilirubin, albumin,
      and liver enzyme levels and INR on postoperative day 4 (POD4) and POD21. RESULTS:
      Two patients died of MRSA sepsis on POD18 and POD23 (MELD: 24 and 28) after
      initial graft function. Their graft weights were 800 g and 980 g, and their
      volumes were 47% (group B) and 62% (group A) of the ideal liver mass of the
      recipients, respectively. One PTF and another cadaveric vascular graft were found
      occluded 4 and 7 days after implantation without any negative consequence. At 6
      month follow-up, the remaining 55 patients were alive with primary liver grafts.
      Vascular reconstructions were patent except for 2 early occlusions. Among the 3
      groups, no significant difference was found on POD4. Three weeks after
      transplantation, the mean AST level in the major ligation group (46.7 +/- 8.14)
      was significantly higher than in the minor ligatation group (29.6 +/- 8.6) but
      not in the major reconstruction group (33.7 +/- 3.7; P = .03 and P = .29). The
      mean albumin level was highest after minor ligation (3.2 +/- 0.18), which was
      significantly better than the major reconstruction (2.7 +/- 0.1) but not the
      major ligation (3.1 +/- 0.14) cohorts (P = .02 and P = .13). CONCLUSIONS: In this
      study of a limited number of cases, right-lobe liver grafts with GRWR of > or
      =1.1% displayed optimal graft function without additional venous reconstruction
      to the AS.

PMID- 17175338
TI  - Liver transplantation in children weighing less than 10 kilograms.
AB  - Orthotopic liver transplantation (OLT) remains a major medical and surgical
      challenge in small pediatric patients. From April 2003 through October 2005, 17
      infants (each of whom weighed less than 10 kg) underwent the procedure. Four were
      girls and 13 were boys (mean age, 15.7 +/- 9.3 months [range, 2-36 months]; mean
      weight at the time of transplantation, 7.4 +/- 2.6 kg [range, 6-10 kg]). All
      transplants were obtained from living-related donors. Sixteen left lateral
      segments and 1 left lobe were transplanted. The median graft-to-recipient weight
      ratio was 3.5% +/- 1.2% (range, 1.5%-6.1%). During the early postoperative
      period, hepatic arterial thrombosis was identified in 2 infants, and a biliary
      leak in 1. Hepatic arterial thrombosis was treated by reanastomosis with
      polytetrafluoroethylene grafting in the first patient and by surgical embolectomy
      in the second. The biliary leak was treated with percutaneous drainage. In 1
      infant, portal vein stenosis, which was identified during the late postoperative
      period, was treated by percutaneous balloon dilatation. At this time, 14 (82.3%)
      infants were alive, exhibiting good graft function at a median follow-up of 11
      months (range, 2-36 months). Three infants died: 1 on postoperative day 47 from
      adult respiratory distress syndrome, 1 on postoperative day 12 from sepsis, and 1
      on postoperative day 65 from sepsis associated with EBV infection. Episodes of
      acute rejection, which occurred in 5 patients, were treated with pulse steroid
      therapy. On follow-up, histologic examination revealed hepatocellular carcinoma
      in 2 infants and Burkitt's lymphoma in 1 infant. Our data confirm that extensive
      use of living-related donors in liver transplantation can result in an excellent
      outcome for small pediatric patients.

PMID- 17175339
TI  - Sonographic differences in venous return between piggyback versus caval
      interposition in adult liver transplantations.
AB  - The piggyback technique (PT) is being used more frequently than caval
      interposition (CI) in adult orthotopic liver transplants (OLT). It is unclear
      whether PT alters venous return compared with CI, therefore leading to
      postoperative complications. The aim of our study was to analyze our experience
      with PT and CI by comparing ultrasound results of hepatic vein flow on the first
      postoperative day. PATIENTS AND METHODS: This retrospective analysis of
      consecutive OLTs performed between 2002 and 2005 included data from a single
      blinded radiologist who reviewed all postoperative day 1 ultrasound examinations.
      The hepatic vein waveforms were scored as all phasic, all flat, or partially
      phasic/flat. RESULTS: During the study period, we performed, 465 OLT among which
      270 had available ultrasound examinations. The etiologies of liver disease were
      similar between the PT and CI cohorts, hepatitis C and alcoholic liver disease
      accounted for more than 60%. Two hundred eight (77%) had undergone PT and 62
      (23%) CI. Among the PT, 60% were phasic, 31.1% were partially phasic/flat, and 8%
      were flat. When a CI was performed, 56.5% were phasic, 35.5% were partially
      phasic/flat, and 8% were flat. CONCLUSIONS: There was no significant difference
      between PT and CI with regard to an effect on hepatic vein waveforms on the first
      operative day. Therefore, there do not appear to be early hemodynamic benefits of
      performing CI versus PT anastamoses of OLTs. Further studies may be needed to
      determine whether long-term sequelae follow the piggyback technique.

PMID- 17175340
TI  - Continuous low-dose human atrial natriuretic peptide promotes diuresis in
      oliguric patients after living donor liver transplantation.
AB  - Human atrial natriuretic peptide (ANP) is beneficial for the prophylaxis of acute
      renal failure (ARF) after liver transplantation (OLT). We evaluated renal
      function in OLT patients with or without ARF, describing cases unresponsive to
      loop diuretics successfully treated with continuous low-dose ANP infusion without
      hemodialysis. Twenty-seven consecutive adult-to-adult living donor liver
      transplantations (LDLTs) were performed in 26 patients. One case was excluded due
      to the need for continuous hemodialysis (HD) during the operation. Of the 26
      cases, 6 (23%, group 2) developed ARF in the first 30 days after LDLT; the other
      20 were ARF-free (group 1). The median follow-up was 24 months. No patient
      required either continuous or intermittent HD. Only one patient died due to
      multiple liver abscesses. Mean preoperative serum creatinine (sCr) value and
      intraoperative blood loss in group 2 were significantly higher than those in
      group 1. Three cases in group 2 failed to improve on high-dose loop diuretics
      with low-dose dopamine, exhibiting fluid overload. The remaining three cases in
      group 2 responded to conventional diuretic treatments. Continuous low-dose ANP
      was started 2, 4, or 5 days after LDLT, and urine output significantly increased
      after ANP administration. The serum creatinine values were 1.1, 1.2, and 1.1 at 1
      month and 1.0, 0.9, and 0.6 mg/dL at 6 months after LDLT. Massive blood loss
      during the operation caused ARF, but did not affect renal function after LDLT.
      Continuous low-dose ANP improved renal function and diuresis for oliguric ARF
      patients, preventing the need for HD or continuous venovenous hemodialysis.

PMID- 17175341
TI  - Acute rejection after liver transplantation: Is there a specific immunological
      pattern?
AB  - The aim of the study was to assess various T-cell subsets and cytokine secretion
      patterns both in liver tissue and in the peripheral blood of 24 liver transplant
      patients to assess possible specific immunological involvement in early acute
      rejection episodes after liver transplantation. Particularly, we studied CD4+
      CD7+, CD8+ CD38+, and CD4+ CD25+ T cells by flow cytometry, as well as
      contemporaneously, interleukin (IL)-2 and IL-10 secretion by ELISpot to determine
      possible Th1-like immune responses and the immunomodulation expressed by Treg
      cells in acute liver rejection, respectively. As a control group we included
      patients transplanted without acute rejection. Early acute rejection within the
      first 4 weeks was proven histologically in 42% of patients. It was associated
      with a greater expression of CD4+ CD7+ and CD8+ CD38+ T cells in the liver than
      in the blood (P < .001). A contemporaneous reduced expansion of liver Treg cells
      was evident in patients with acute rejection (P < .001). Our data suggested that
      a preferential Th1-like immune mechanism operated in local fashion as
      characterized by a decreased presence in the liver and blood of Treg cells.

PMID- 17175342
TI  - c-Kit-positive mast cells in portal tracts cannot be used to distinguish acute
      cellular rejection from recurrent hepatitis C infection in liver allografts.
AB  - Cirrhosis secondary to chronic hepatitis C virus (HCV) is the most common
      indication for liver transplantation. Recurrence of HCV infection in the liver
      allograft occurs at a high rate. The differentiation of recurrent HCV infection
      from acute cellular rejection (ACR) represents a difficult challenge in
      transplantation pathology. The c-Kit receptor is a tyrosine kinase membrane
      protein encoded by the c-Kit proto-oncogene, which is expressed on mast cells and
      on hematopoietic stem and progenitor cells. Mast cells are important effector
      cells of a broad range of immune responses. Recently, c-Kit+ mast cells were
      shown to form part of the inflammatory infiltrate in acute liver allograft
      rejection. A strong relationship was found between c-Kit+ cell densities and
      increasingly severe rejection. The present study sought to determine whether the
      presence of c-Kit+ cells could be used to distinguish between ACR and recurrent
      HCV in liver allografts. Immunohistochemical staining for c-Kit was performed on
      20 transplant biopsy specimens from 10 patients with mild to moderate ACR and 10
      other patients with recurrent hepatitis C. The number of c-Kit+ cells per portal
      tract varied with the density of the overall inflammatory infiltrate. There was
      no significant difference between the number of c-Kit+ cells in the biopsy
      specimens that carried a diagnosis of ACR and those from patients who had been
      diagnosed as having recurrent HCV. It was concluded that immunohistochemical
      staining for the presence of c-Kit+ mast cells cannot be used to differentiate
      between ACR and recurrent HCV infection in liver allograft biopsy specimens.

PMID- 17175343
TI  - High serum soluble CD30 does not predict acute rejection in liver transplant
      patients.
AB  - Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been
      shown to be associated with acute kidney transplant rejection. We sought to study
      whether high sCD30 could predict rejection early after liver transplantation. The
      study population included 54 consecutive liver transplant patients, whose samples
      were collected before liver transplantation and at discharge, which was at a mean
      time of 3 weeks after transplantation. During the first 6 months
      posttransplantation, 22 patients experienced an acute rejection episode. Serum
      sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in
      serum sCD30 levels posttransplantation were also expressed as relative values
      compared with pretransplantation results. Liver patients before transplantation
      displayed higher serum sCD30 values compared with healthy controls: mean values
      +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after
      transplantation the mean sCD30 concentration in liver transplant patients
      decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30
      value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43
      IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups
      decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs
      69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3
      weeks posttransplantation decreased slightly more among patients with vs without
      rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti
      HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor
      posttransplantation sCD30 levels were associated with acute rejection in liver
      transplant patients.

PMID- 17175344
TI  - Role of antinuclear antibodies in experimental and clinical liver
      transplantation.
AB  - OBJECTIVE: We recently reported that autoreactive antibodies (Abs) against
      nuclear histone H1 was transiently induced at an early phase after orthotopic
      liver transplantation (OLT) in a tolerogenic rat OLT model and possessed
      immunosuppressive activity. It was also reported that nuclear antigen, high
      mobility group box 1 (HMGB1) protein was one of the initiators of the immune
      reaction. The present study sought to evaluate the role of antinuclear Abs in
      experimental and clinical liver transplantation. MATERIALS AND METHODS: We
      prepared 3 animal models: natural tolerance model (DA liver into PVG); acute
      rejection model (DA liver into LEW); and drug-induced tolerance model (acute
      rejection model + cyclosporine [CsA]). In addition, we examined clinical samples,
      including 1 drug-free patient, to measure the antihistone H1/HMGB1 titers at
      various times after OLT. RESULTS: In a natural tolerance model, antihistone H1
      and HMGB1 Ab was induced during the rejection and the tolerance induction phases,
      respectively. Those Ab responses were also confirmed in a drug-induced tolerance
      model, whereas no such responses were shown in an acute rejection model. In our
      clinical drug-free patient, antihistone H1/HMGB1 titer was significantly higher
      after cessation of CsA than that in healthy volunteers. CONCLUSIONS: Antinuclear
      Ab is actively expressed in accordance with overcoming rejection episodes with
      subsequent tolerance induction in both a natural tolerance model and a drug
      induced tolerance model. We also observed a similar tendency in our clinical drug
      free patient. These results suggested that antinuclear Abs may be useful markers
      to determine the timing to withdraw immunosuppressants.

PMID- 17175345
TI  - Routine use of auxiliary partial orthotopic liver transplantation for children
      with fulminant hepatic failure: Preliminary report.
AB  - Auxiliary partial orthotopic liver transplantation (APOLT) has been performed for
      both metabolic disorders and fulminant liver failure (FHF). When the native liver
      regenerates, the patients with FHF who undergo APOLT have a chance to withdraw
      immunosuppression. It may be most beneficial for children. This preliminary
      report describes our start to routinely offer APOLT as an option to standard OLT
      for children with FHF in 2005. Six children (ages 8 months to 8 years) received
      APOLT: 1 in 1996 and the others in 2005 and 2006. The donor ages ranged from 4 to
      40 years. We used either a left lateral segment or a left lobe graft. The
      recipient left lobe, which was removed, showed submassive to massive necrosis at
      the time of transplantation. All children are alive and well. The first patient
      who received APOLT in 1996 is currently off immunosuppression with a fully
      recovered native liver; the grafted liver underwent complete atrophy. The 5
      remaining subjects are receiving reduced levels of immunosuppression with close
      monitoring. Their serial liver biopsy specimens show slight to significant
      recovery. One developed hepatic artery thrombosis, requiring retransplantation.
      The native liver was retained at the time of retransplantation (redo APOLT).
      Other postoperative complications included a bile leak (n = 1), invasive
      mucomycosis of the arm (preexisting condition; n = 1), biliary stricture (n = 1),
      and acute cellular rejection (n = 3). Posttransplantation length of stay was 6 to
      60 days (median, 15 days). In conclusion, APOLT can be safely performed in
      children with FHF displaying short-term outcomes comparable to standard
      transplantations.

PMID- 17175346
TI  - Pediatric liver transplant with Campath 1H induction--Preliminary report.
AB  - Since Campath 1H (C1H) has been successfully used in adult liver transplant
      recipients since 2001 in our program, we started to use it in children. PATIENTS
      AND METHODS: C1H induction was employed in 10 children with autoimmune hepatitis
      (AIH) (n = 6), primary sclerosing cholangitis (PSC) (n = 1), biliary atresia (n =
      1), glycogen storage disease (n = 1), and Wilson's disease. Eight were primary
      transplants, and two retransplants. Patients ages ranged from 5 to 17 years. C1H
      was administered at a dose of 0.3 mg/kg on days 0, 4, and 7. Tacrolimus level was
      maintained at 5 to 10 ng/mL. No patient received maintenance steroids
      posttransplantation except two who were on steroid therapy at the time
      transplant. They were prescribed small doses of maintenance steroids. Median
      follow-up of C1H recipients was 679 days (range 115-1143). RESULTS: Postoperative
      courses were mostly uneventful except for one retransplant recipient who required
      prolonged hospitalization (40 days) for rehabilitation. Median hospital stay was
      12 days (range 7-40 days). All 10 patients in the C1H group are currently alive
      and well with stable graft function. No opportunistic infection was observed in
      these patients to date. We compared six patients with AIH who received C1H to the
      historic control of 10 recipients with AIH who received conventional
      immunosuppression (tacrolimus + steroid). The patients treated with C1H showed
      significantly prolonged rejection-free survival. CONCLUSION: In our preliminary
      experience, C1H induction was well tolerated in pediatric liver recipients.
      Rejections-free survival was prolonged among recipients with AIH despite a low
      level of maintenance immunosuppression.

PMID- 17175347
TI  - Clinical and financial impact of obesity on the outcome of liver transplantation.
AB  - The purpose of this study was to determine whether body mass index (BMI)
      influences the clinical outcomes and overall cost of transplantation in adult
      liver transplantation (OLT) using records of 700 adult OLT recipients. Patients
      were divided into BMI range groups over the range of 15 to 42 (mean = 26.7),
      namely: <25, n = 288 (41%); 25 to 30, n = 245 (35%); > or =30, n = 167 (24%).
      Only a small subset of this last group was morbidly obese (BMI > or = 35, n = 37,
      5% of total). We did not detect an effect of BMI on patient or graft survival,
      the incidence of acute graft rejection, or major surgical complications. BMI was
      not related to length of hospital stay. There were no statistical differences
      between the three groups with respect to the ratio of overall hospital cost in a
      general linear model, corrected for age, gender, calculated Model for End-Stage
      Liver Disease score, retransplant status, or return to the operating room. In
      conclusion, obesity did not influence either the costs or the clinical outcomes
      following OLT. Further analysis of the morbidly obese population with respect to
      cost and outcome is warranted.

PMID- 17175348
TI  - Successful staged kidney and liver transplantation for glycogen storage disease
      type Ib: A case report.
AB  - Glycogen storage disease type Ib is a rare metabolic disease caused by a defect
      of the G6P transporter. Patients suffer from hypoglycemic episodes; growth and
      developmental delay; osteoporosis; neutropenia; and tendency to infections,
      ovarian cysts, and liver adenomas. Terminal kidney disease is a rare
      complication. Liver transplantation has been performed to prevent malignant
      transformation of hepatic adenomas. We present the case of a female patient with
      glycogenosis type Ib who had severe hypoglycemic episodes and recurrent
      infections since early childhood. She became dialysis dependent at the age of 24
      years. Kidney transplantation was performed at age 30, and liver transplantation
      2 years later. The main indication for liver transplantation were the persistent,
      therapy-refractory hypoglycemic episodes. The transplanted kidney function is
      stable. The liver transplantation resulted in the disappearance of hypoglycemic
      episodes, with the patient leading a normal life and eating a normal diet. The
      neutropenia did not recover, but there were no more significant infectious
      episodes after liver transplantation. This is, to the best of our knowledge, the
      first communication of a dual kidney and liver transplant performed in a patient
      with glycogenosis type Ib. It confirmed the beneficial effect of liver
      transplantation on the quality of life of patients with severe hypoglycemia. The
      transplantation should be attempted earlier in the course of the disease to
      reduce complications and allow catch-up growth. Hepatocyte transplantation may be
      considered; however, long-term results seem to be rather poor in the few
      documented cases.

PMID- 17175349
TI  - Recovery from liver dysfunction after adult isolated intestinal transplantation
      without liver grafting.
AB  - PURPOSE: We sought to evaluate liver function recovery after isolated intestinal
      transplantation in adults with irreversible intestinal failure. PATIENTS AND
      METHODS: Over a 5-year period, we transplanted 34 adult patients, 25 of whom
      received an isolated intestinal graft, 4 a multivisceral graft without a liver,
      and 5, a multivisceral graft with a liver. Among the group of patients
      transplanted with the isolated graft we selected 14 recipients with pretransplant
      liver dysfunction, namely, a serum bilirubin >2 mg/dL (normal value: 1.2) and/or
      transaminases >100 IU/mL (NV, 37/40). Other inclusion criteria were total
      parenteral nutrition, period > 3 months, no diagnosis of portal hypertension or
      cirrhosis. Two patients had biopsy-proven liver fibrosis. RESULTS: At discharge,
      all patients recovered liver function to normal values: mean bilirubin blood
      level was 0.9 +/- 0.96 mg/dL (range: 0.3-1.6) and mean transaminases were 26 +/-
      9 and 31 +/- 18 IU/mL (range: 10-44/27-65). After a mean follow-up of 2 years,
      only one patient has an elevated alanine aminotransferase level without clinical
      signs of liver disease. Type of pretransplant liver disease did not impact on
      survival rates. CONCLUSION: In selected cases, an isolated intestinal or a
      multivisceral graft without a liver can represent a "liver salvage therapy" for
      an early failing liver in patients with irreversible intestinal failure.
      Pretransplant liver disease is not a negative prognostic factor.

PMID- 17175350
TI  - A cyclosporine-based immunosuppressive regimen may be better than tacrolimus for
      long-term liver allograft survival in recipients transplanted for hepatitis C.
AB  - Rapid recurrence of severe hepatitis C (HCV) after liver transplantation is a
      major barrier to survival of the transplanted liver. While cyclosporine (CsA) in
      vitro has been shown to suppress HCV replication, an effect is not seen with
      tacrolimus (Tac). Evidence is inconsistent whether or how this translates to
      clinical practice. To expand the evidence on this issue, we analyzed graft
      survival and histological outcomes after liver transplantation for HCV hepatitis.
      METHODS: Using our longitudinal database (1991 onward) graft outcomes for all
      liver transplant recipients with HCV were evaluated (105 grafts in 97 patients).
      Severe activity, severe fibrosis, and graft survival were analyzed. All liver
      biopsies were scored (blinded) according to the Ludwig scale. Immunosuppression
      was based on prednisone and a calcineurin inhibitor (Tac n = 89, 85%; CsA n = 15,
      14%). Comparisons of outcomes using CsA versus Tac therapy were done using
      survival analysis via the log-rank test. RESULTS: Graft survival was
      significantly better in the CsA group. Although there was no apparent difference
      in severe activity (grade 2), there was a statistically significant difference in
      graft survival without fibrosing cholestatic hepatitis (P = .01) and a trend
      toward a difference in fibrosis-free survival (P = 0.1). The rate of sustained
      response to antiviral therapy was twice as high in the CsA group, 50% versus 22%
      (P = 0.16; NS). CONCLUSIONS: Graft survival in liver transplant recipients with
      HCV may be greater with CsA-based immunosuppression. There may also be a lower
      rate of fibrosing cholestatic hepatitis in this group.

PMID- 17175351
TI  - The role of plasmapheresis therapy for perioperative management in ABO
      incompatible adult living donor liver transplantation.
AB  - BACKGROUND: Although living donor liver transplantation (LDLT) was established as
      a treatment for end-stage liver disease in Japan, the indication for LDLT across
      an ABO-incompatible barrier remains controversial. The purpose of this study was
      to elucidate the role of plasmapheresis in incompatible LDLT. METHODS: Eleven
      adult patients (seven men and four women) who underwent incompatible LDLT were
      enrolled in this study. Of these three patients had hepatocellular carcinoma,
      three chronic hepatitis C, one Wilson's disease, one autoimmune hepatitis, one
      chronic hepatitis B, one hemochromatosis, and one fulminant hepatic failure. The
      immunosuppressive regimen consisted of tacrolimus, prednisolone, mycophenolate
      mofetil (or cyclophosphamide), and prostaglandin E1 in all patients. Multiple
      plasmapheresis was performed perioperatively to reduce the recipient's antibody
      titers against the donor's blood type. RESULTS: Plasmapheresis was useful for the
      reduction of the recipient's antibody titers to x 16 or lower before and after
      transplantation. There was no difference in transplant outcome between the 11
      patients with incompatible blood group and 30 patients with identical or
      compatible blood groups. DISCUSSION: Major postoperative complications such as
      intrahepatic biliary complications and hepatic necrosis may occur in incompatible
      transplantation. Several investigators suggested that anti-immunoglobulin (Ig) M
      and anti-IgG antibody titers sustained these complications. The antibody titers
      must be decreased sufficiently with plasmapheresis. An elevation of anti-ABO
      titers after transplantation may be a predictive risk factor for increased
      mortality and morbidity. In order to perform LDLT in a safer manner,
      plasmapheresis is an indispensable treatment to improve the outcome of ABO
      incompatible cases.

PMID- 17175352
TI  - Basiliximab induction in adult liver transplant recipients with 93% rejection
      free patient and graft survival at 24 months.
AB  - Induction with the use of interleukin-2 receptor monoclonal antibodies may avoid
      many of the adverse events associated with polyclonal antibodies and
      significantly impact on rejection-free long-term survival in orthotopic liver
      transplantation (OLTx). We describe our experience with the use of basiliximab
      induction therapy in adult OLTx recipients on tacrolimus-based immunosuppression.
      Forty-six consecutive deceased donor primary OLTx were analyzed. All patients
      received standard doses of basiliximab, tacrolimus, and steroids. Mycophenolate
      mofetil was also used as indicated. The mean follow-up period was 17.9 months.
      Forty-three patients remained rejection-free during follow-up. The actuarial
      patient and graft survival rate at 2 years was 93%. The rate of histology-proven
      hepatitis C virus (HCV) recurrence was 24%, with two progressing to severe
      cholestatic recurrent HCV. None of the study patients developed (cytomegalovirus
      (CMV) infection or posttransplant lymphoproliferative disease (PTLD). Results
      were compared to a historical group of 46 OLTx recipients on tacrolimus-based
      immunosuppression without basiliximab induction. The historical group had a
      rejection rate of 34% with lower patient and graft survival rates of 71.74% and
      69.5%, respectively, at 24 months as well as a higher histological HCV recurrence
      rate of 77% (17/22), with three patients progressing to graft failure within 2
      years. CMV infection and disease developed in 4.5% of the patients. Although PTLD
      was not observed, three recipients with hepatocellular carcinoma (HCC) developed
      and died of metastatic HCC. Induction with basiliximab in combination with
      tacrolimus-based immunosuppressive regimen reduces the incidence of rejection and
      improves rejection-free survival rate after OLTx without increasing the incidence
      of CMV, PTLD, or HCV recurrence.

PMID- 17175353
TI  - Comparison between human-telomerase reverse transcriptase mRNA and alpha
      fetoprotein mRNA as a predictive value for recurrence of hepatocellular carcinoma
      in living donor liver transplantation.
AB  - OBJECTIVE: In this study we compared the potential roles of preoperative human
      telomerase reverse transcriptase (h-TERT) mRNA versus alpha-fetoprotein (AFP)
      mRNA expression in the peripheral blood as a tool to predict prognosis and tumor
      recurrence after living donor liver transplantation (LDLT) in hepatocellular
      carcinoma (HCC) patients. PATIENTS AND METHODS: We examined 14 patients with
      unresectable HCC who underwent LDLT. Six patients displayed stage IVA HCC that
      deviated from the Milan criteria, while the rest of the patients fell within the
      limitations of the Milan criteria. We analyzed the relationship between
      preoperative h-TERT mRNA or AFP mRNA expression in the peripheral blood and
      survival without recurrence. RESULTS: There was no significant difference between
      the survival curves without recurrence of those patients who did versus did not
      meet the Milan criteria. There was also no significant difference between the
      survival curves without recurrence among patients with positive versus negative
      AFP mRNA expression. However, there was a significant difference (P = .005)
      between the survival curves without recurrence of those patients with positive
      preoperative h-TERT mRNA expression versus those who either had an initially
      negative preoperative h-TERT mRNA or who converted from positive to negative
      after neoadjuvant immunochemotherapy. CONCLUSIONS: h-TERT mRNA seemed to prove
      more valuable than AFP mRNA not only to assess preoperative treatment modalities
      and postoperative patient surveillance, but also to evaluate prospective LDLT
      patients with HCC. Moreover, use of h-TERT mRNA could potentially expand the
      indications for transplantation to patients outside the Milan criteria.

PMID- 17175354
TI  - Alpha-fetoprotein mRNA detection in peripheral blood for prediction of
      hepatocellular carcinoma recurrence after liver transplantation.
AB  - The aim of this study was to assess the value of alphafeto protein (AFP) mRNA
      expressing cells detected in peripheral blood for predicting tumor recurrence
      after living donor liver transplantation (LDLT) in patients with hepatocellular
      carcinoma (HCC). The test group consisted of 25 patients who underwent LDLT for
      end-stage liver disease with HCC while the control group consisted of 37 living
      donors. Quantitative real-time reverse-transcriptase polymerase chain reaction
      was used for detection of AFP mRNA-expressing cells in peripheral blood. Nine
      (36%) of 25 patients developed tumor recurrences (four lung; one liver; one
      peritoneum; two bone; one adrenal gland) during the follow-up period.
      Perioperatively, AFP mRNA was positive in peripheral blood of eight patients
      (32.0%) but only in 1 (2.7%) of the control. Preoperative AFP mRNA was positive
      in three cases. Univariate analyses revealed that preoperative and perioperative
      AFP mRNA and microscopical vascular invasion were the significant predictors for
      HCC recurrence (P = .007, .037, and .005, respectively). In the patients with HCC
      exceeding Milan criteria (n = 15), the presence of AFP mRNA-positive cells in the
      peripheral blood correlated significantly with HCC recurrence (P = .033). We
      concluded that the presence of AFP mRNA-expressing cells could be a useful
      predictor of HCC recurrence in liver transplant patients.

PMID- 17175355
TI  - Influence of hepatitis C on renal function after liver transplantation.
AB  - Liver transplantation (OLT) is often complicated by renal failure. Hepatitis C
      (HCV) is said to be a risk factor for renal failure after OLT, but few studies
      have analyzed this directly. We evaluated all patients who received a liver
      transplant from 1995 through 2003. There were 147 patients infected with HCV and
      202 not infected. Patients with HCV were further divided into 114 patients with
      benign HCV and 33 patients with severe HCV defined by bridging fibrosis or
      cirrhosis. The groups were evaluated for the development of renal insufficiency
      defined as a creatinine above 1.8 mg/dL on three consecutive occasions or renal
      failure as defined by the need for dialysis or renal transplant. The incidence of
      renal failure in patients with HCV was 10.2% and in patients without HCV was 3.5%
      (P = .004). Patients with severe HCV had an incidence of 12.1% vs 9.7% for
      patients with mild HCV. The linear trend in renal failure from non-HCV to mild
      HCV to severe HCV was significant (P = .012). The incidence of renal
      insufficiency was 23.4% in patients with HCV and 14.9% in patients without HCV (P
      = .080). The incidence was 32.3% in patients with severe HCV and 20.6% in
      patients with mild HCV. The trend in renal insufficiency across the three groups
      was mildly significant (P = .042). On multivariate analysis, HCV was a risk
      factor for renal failure with a relative risk of 2.58 (P = .045). The study
      suggests that HCV and the severity of recurrent HCV are risk factors for renal
      dysfunction after liver transplantation.

PMID- 17175356
TI  - Blood gene expression profiling in liver transplant recipients with hepatitis C
      virus and posttransplantation diabetes mellitus.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a risk factor for developing
      posttransplantation diabetes mellitus (PTDM) after liver transplantation; little
      is known about the biological mechanisms involved with this risk. This study
      investigated gene expression differences to provide insight into potential
      mechanisms. PATIENTS AND METHODS: Gene expression profiles of blood samples
      obtained from 6 HCV+ liver transplant recipients were determined using Affymetrix
      U133 Plus 2.0 microarrays. Differential gene expression was assessed between HCV+
      recipients with PTDM (n = 3) and without PTDM (n = 3) using the GeneSpring 7.3
      software package. The Welch t test was used to identify significant differences
      (P < .05) between groups. Gene expression profiles for 6 HCV- liver transplant
      recipients (with PTDM = 3, without PTDM = 3) were used as a blind test set to
      evaluate a subset of genes to predict PTDM. RESULTS: Expression levels of 347
      genes were significantly different between recipients with PTDM and those without
      PTDM. Seventy-four genes were up-regulated and 270 were down-regulated in PTDM.
      Genes were categorized into functional classes: apoptosis (n = 69 genes); immune
      function (n = 110); diabetes (n = 17); hepatitis C (n = 12); liver transplant (n
      = 69). The expression profile of a subset of genes was evaluated for predicting
      PTDM in 6 HCV- transplant recipients. We accurately predicted the presence or
      absence of PTDM in 5/6 recipients. CONCLUSIONS: PTDM in HCV+ liver transplant
      recipients was associated with down-regulated expression of a large number of
      genes. A subset of these genes was useful to predict PTDM in HCV- recipients.
      Most genes were associated with apoptosis and immune function. HCV may act as a
      primer by affecting a group of genes involved in developing diabetes.

PMID- 17175357
TI  - Effects of hepatic CYP3A4 activity on disposition of micafungin in liver
      transplant recipients with markedly small-for-size grafts.
AB  - Micafungin, the first candin antifungal drug developed in Japan, has a
      significant therapeutic effect against deep-seated mycoses caused by Candida or
      Aspergillus. Little is known, however, about the optimal dosage or disposition of
      micafungin in patients with severe hepatic impairment. Nine liver transplant
      recipients (5 males and 4 females) were enrolled in this study. In 1 recipient
      with a markedly small-for-size graft (ratio of graft volume to standard liver
      volume at the time of transplantation: 25.9%), the areas under the plasma
      concentration-time curves up to 12 hours postdose (AUC(0-12 h)) at doses of 50
      and 100 mg/d were 79.38 and 601.17 mug.h/mL, respectively. The corresponding
      elimination half-life (T(1/2)) values were 16.01 and 75.75 hours, and saturated
      elimination was observed only at the dose of 100 mg/d. The mean urinary ratio of
      6beta-hydroxycortisol to cortisol (6beta-OHF/F) in the small-for-size graft
      recipient was significantly (P < .05) lower than that in the other recipients. In
      conclusion, graft size was an important factor affecting disposition of
      micafungin. For liver transplant recipients with markedly small-for-size grafts,
      the optimal dosage of micafungin to reach and maintain therapeutic plasma levels
      is estimated to be 50 mg/d.

PMID- 17175358
TI  - Arterial steal syndrome after orthotopic liver transplantation.
AB  - Arterial steal syndrome after orthotopic liver transplantation (OLT) is
      characterized by arterial hypoperfusion of the graft, which is caused by a shift
      in blood flow into the splenic or gastroduodenal arteries. In this report, we
      present mechanisms by which this syndrome caused ischemia in our patients. Steal
      was suspected by elevated levels of liver enzymes and the results of Doppler
      ultrasonography and computed tomographic angiography; it was confirmed by celiac
      angiography. Patients with established hepatic arterial thrombosis before
      angiography were excluded from this study. Steal was treated by embolization with
      a coil or by placement of an endoluminal narrowing stent. Ten patients at our
      institution (seven men and three women; mean age, 24.7 +/- 11 years; range, 6 to
      40 years) exhibited biochemical evidence of liver ischemia and graft failure at 1
      to 170 days after having undergone orthotopic liver transplantation. Nine of
      those patients had splenic steal, and one had both splenic and left gastric
      artery steal syndrome. None of the patients had gastroduodenal artery steal
      syndrome. The eight patients with splenic steal syndrome and the patient with
      both splenic and left gastric steal syndrome were treated by transcatheter
      occlusion with a coil. The remaining patient with splenic steal syndrome was
      treated with an endoluminal narrowing stent placement. All patients improved
      clinically within 24 hours after treatment, exhibiting significant changes in
      their biochemical and radiological parameters. Follow-up ranged from 1 to 22
      months (mean, 6.7 +/- 6.6 months). One patient died from sepsis 1 month after
      having undergone coil embolization. He had no vascular anomalies at the time of
      death. We conclude that steal is a significant problem after OLT. Embolization
      and stenting are minimally invasive and successful treatments for steal, usually
      resulting early clinical improvement.

PMID- 17175359
TI  - Stent placement in pediatric patients with hepatic artery stenosis or thrombosis
      after liver transplantation.
AB  - Hepatic artery stenosis (HAS) and thrombosis (HAT) after orthotopic liver
      transplantation remain significant causes of graft loss. Postoperative HAT
      follows approximately 5% to 19% of orthotopic liver transplantation. It is seen
      more frequently in pediatric patients. In the past, repeat transplantation was
      considered the first choice for therapy. Recently, interventional radiological
      techniques, such as thrombolysis, percutaneous transluminal angioplasty, or stent
      placement in the hepatic artery, have been suggested, but little data exist
      related to stent placement in the thrombosed hepatic artery during the early
      postoperative period in pediatric patients. Between March 2000 and March 2005,
      percutaneous endoluminal stent placement was performed in seven pediatric liver
      transplant patients. HAT or HAS initially diagnosed in all cases by Doppler
      ultrasound then confirmed angiographically. We intervened in four cases of
      hepatic artery stenosis and three cases of hepatic artery occlusion. Stents were
      placed in all patients. Three ruptures were seen during percutaneous transluminal
      angioplasty of the hepatic artery using a covered coronary stents on the first,
      fifth day, or 17th postoperative day. In one patient, dissection of the origin of
      the common hepatic artery developed owing to a guiding sheath, and a second stent
      was placed to cover the dissected segment. The other two hepatic artery stents
      remained patent. In one stent became occluded at 3 months after the intervention
      with no clinical problems. Follow-up ranged from 9 to 40 months. In conclusion,
      early and late postoperative stent placement in the graft hepatic artery was
      technically feasible.

PMID- 17175360
TI  - Effect of early recurrence of hepatitis C on late biliary anastomotic stricture
      after liver transplantation.
AB  - The aim of the current study was to clarify whether recurrence of hepatitis C
      (HCV) infection affects biliary complications after liver transplantation (OLT),
      with special reference to late biliary anastomotic strictures (LBAS). We reviewed
      665 consecutive adult OLT recipients with a choledochocholedochostomy without T
      tube placement between 1990 and 2005. Biliary anastomotic stricture was confirmed
      by ERCP. The LBAS was defined as stricture that occurred 30 days or more after
      OLT. Recurrence of HCV was diagnosed by histological examination using liver
      biopsy specimen and confirmed by the presence of HCV-RNA. Early HCV recurrence
      was defined as recurrence that occurred within 6 months after OLT; LBAS occurred
      in 54 patients (8% of total). Mean duration from OLT to occurrence of LBAS was
      6.9 months (1-44 months). Patients with HCV infection had higher occurrence of
      LBAS than did non-HCV patients (11% vs 5%, P = .0093). Among HCV patients, those
      with early HCV recurrence had exclusively high rate of LBAS (16%). In
      multivariate analyses, early recurrence of HCV (P < .001, relative risk [RR]
      6.4), as well as occurrence of HAT (P = .0018, RR 8.0), and prolonged CIT (P =
      .034, RR 3.3) were independent risk factors affecting LBAS. In conclusion,
      patients with HCV infection have increased occurrence of LBAS after OLT.
      Additionally, early recurrence of HCV contributes to a higher rate of LBAS.

PMID- 17175361
TI  - Renal disease burden following liver transplantation.
AB  - Significant chronic kidney disease (CKD) occurs following orthotopic liver
      transplant (OLT). Since CKD is associated with increased cardiovascular events,
      mortality, and hepatic allograft dysfunction, early recognition of CKD and
      implementation of changes may improve the long-term outcome. The purpose of this
      study was to determine the burden of renal disease following OLT. PATIENTS AND
      METHODS: We retrospectively reviewed our OLT recipients from 1997 until 2004. We
      calculated glomerular filtration rates (GFR) using the Modification of Diet in
      Renal Disease study (MDRD) method. The GFRs were further subdivided into pre-MELD
      and post-MELD eras. RESULTS: During the study period, we performed 407 OLTs. We
      censored data from living donor liver transplants (n = 14), combined liver-kidney
      transplants (n = 12), and from patients whom we did not have complete data for 6
      months after transplant (n = 40). Mean MELD score at the time of transplant was
      18 +/- 7 (mean +/- standard deviation). The mean GFR at 6 months following OLT
      was 63.7 +/- 30.2 mL/min per 1.73 m(2). Only 14% (n = 47) of our patients had
      normal renal function at 6 months, while 78% (n = 266) of our patients had mild
      to moderate risk for renal failure. Eight percent (n = 28) had stage 4 or 5 CKD.
      There were no differences between the pre-MELD and post-MELD GFRs. CONCLUSIONS:
      The burden of renal disease is significant in our patient population at 6 months
      posttransplantation. It may be important to introduce CKD management as early as
      6 months after transplant to impact the outcomes of OLT recipients.

PMID- 17175362
TI  - Prevalence and clinical course of BK virus nephropathy in pancreas after kidney
      transplant patients.
AB  - The influence of BK virus nephropathy (BKVN) in pancreas after kidney (PAK)
      transplantation is unclear. A retrospective analysis of PAK transplants performed
      at our center was conducted to determine the impact of BKVN. Among 40 PAK
      transplants performed using sequential immunosuppression, four patients developed
      BKVN, as defined by a >20% rise in serum creatinine and BK viremia (BK plasma
      load >4 log copies/mL), at a median of 19 months following PAK. In all four
      patients, treatment of BKVN consisted of reduction in tacrolimus, cessation of
      mycophenolate mofetil, and introduction of leflunomide. With this approach, two
      patients experienced improvement or stabilization of renal function. The
      remaining two patients progressed to dialysis dependence despite treatment.
      Plasma BK load < or =5 log copies/mL was associated with graft preservation.
      Gender, age, delay between transplants, cumulative Thymoglobulin dose, and type
      of kidney donor were not associated with BK virus infection. Pancreas graft
      rejection or dysfunction was not observed with the above immunosuppression
      modification. Mean amylase and lipase > or =6 months following BKVN treatment
      remained normal. BKVN is an important cause of kidney allograft loss in PAK
      patients. Screening and early treatment of BKVN may enable preservation of kidney
      and pancreas grafts.

PMID- 17175363
TI  - Efficacy of valganciclovir in the treatment of cytomegalovirus disease in kidney
      and pancreas transplant recipients.
AB  - Cytomegalovirus (CMV) disease is relatively common following solid organ
      transplant, particularly if a serologically negative recipient receives an organ
      from a serologically positive donor (D+/R-). Although valganciclovir is approved
      for the treatment of CMV retinitis in AIDS patients and is used for the
      prophylaxis against CMV infection in solid organ transplant patients, the current
      standard treatment for CMV disease in solid organ transplant recipients remains
      intravenous ganciclovir. We retrospectively reviewed our experience using
      valganciclovir as treatment for CMV disease in CMV D+/R- kidney and/or pancreas
      transplant recipients from March 2002 to June 2005. A total of 37 cases with
      primary CMV disease were diagnosed and treated with either intravenous
      ganciclovir as induction followed with valganciclovir or valganciclovir from the
      beginning. We compared clinical outcomes and viremia between the two groups. Our
      data suggest that valganciclovir is an effective treatment modality for primary
      CMV disease in kidney and/or pancreas transplant recipients. It led to the
      resolution of disease and undetectable viremia. Valganciclovir allowed for early
      initiation of treatment and for treatment to be given as an outpatient. These
      advantages of valganciclovir have both health and economic impact for patients
      with CMV disease.

PMID- 17175364
TI  - Serial peripheral blood cytotoxic lymphocyte gene expression measurements for
      prediction of pancreas transplant rejection.
AB  - Acute rejection after pancreas transplantation remains a significant problem and
      contributes to immunological graft loss. No clinical markers of pancreas
      rejection have been universally accepted. The purpose of this study was to
      investigate the use of genetic markers; granzyme B, perforin, and HLA-DRA in the
      peripheral blood of pancreas transplant recipients. These genes have been
      identified in renal and islet cell transplant recipients as noninvasive tools to
      predict acute rejection. Blood samples were collected weekly for up to 1 year
      posttransplant. Surveillance biopsies of the pancreas were scheduled at weeks 2,
      4, 8, and 12 as part of the typical posttransplant protocol for patients with
      pancreas alone or pancreas after kidney transplantation. Exclusion criteria
      included a diagnosis of biopsy-proven chronic rejection alone, pancreatitis, or
      kidney rejection within 2 months after pancreas biopsy. Gene expression levels of
      granzyme B, perforin, and HLA-DRA were compared in patients with (n = 7) and
      without biopsy proven acute rejection (n = 7). Recipients with acute rejection
      showed increased expression of granzyme B, HLA-DRA, as well as perforin genes
      compared to patients without biopsy-proven rejection. In addition, we observed
      that elevation of these genes occurred as early as 4 weeks before the traditional
      biopsy diagnosis, while the recipients with no rejection showed no change in gene
      expression. Our data indicated that serial measurements of peripheral blood
      granzyme B, perforin, and HLA-DRA gene expression can be a useful tool to predict
      pancreas rejection in its earliest stage.

PMID- 17175365
TI  - Examination of gene expression profile of functional human pancreatic islets
      after 2-week culture.
AB  - Islet transplant faces significant challenges, mainly because of the high
      incidence of primary nonfunction of transplanted islets. Protocol modifications
      to improve the rate of islet function have included changes in pancreatic
      preservation and the introduction of short-term culture. Islet culture for 48 to
      72 hours has become a standard part of most successful protocols for clinical
      islet transplantation. We have previously reported gene expression profiles
      associated with human pancreatic islet function. The aim of this study was to
      determine the change in gene expression profiles of functional islets after 2
      weeks of culture in Memphis-serum free media. Human islets from four isolations
      were maintained in culture for 14 days in Memphis-serum free media. RNA was
      extracted from 10000 IEQ for analysis of the gene expression profiles using high
      density Affymetrix U133A GeneChips and Genespring software. Islet function was
      assessed by measurements of human C-peptide at days 7 and 14 posttransplant into
      NOD-SCID mice. Human C-peptide levels were determined by radioimmunoassay. Our
      preliminary data showed that genes related to functionality, such as those
      directed toward insulin processing and secretion, did not vary over 14 days of
      culture, while genes related to exocrine pancreas and organ architecture and
      immune-associated genes decreased over time. The ability to maintain islets in
      culture is an important step toward the development of islet tissue repositories,
      as well as toward screening human islet preparations for additional pathogens.

PMID- 17175367
TI  - Impact of donor and recipient factors on allograft survival in lung
      transplantation: A single-center analysis.
AB  - BACKGROUND: It remains unclear which donor and recipient factors influence long
      term allograft function in lung transplantation (LTx). METHODS: From October 1988
      to February 2005, a total of 280 recipients underwent LTx at our center. Donor
      data and cause of death (CoD) were analyzed. The CoD was categorized according to
      rate of increase in intracranial pressure at the time of death. Each donor and
      recipient factor was correlated with long-term graft function. Recipient details,
      type of transplant, indication for transplant, and time on waiting list were
      analyzed. Recipients were stratified based on allograft ischemia time (AIT): 0 to
      6, 6 to 8, 8 to 10, and >10 hours. RESULTS: Mean donor age was 30.9 years (36.7%
      male); 49.8% were cytomegalovirus (CMV) positive. Donor CoD was characterized by
      a slow rise in intracranial pressure (ICP) in 34.4%, rapid ICP in 18.7%, an
      intermediate ICP in 44.3%, and with no rise in 2.6%. A graft survival benefit was
      seen with female donors (P = .048); 34.4% of recipients ultimately developed
      graft failure at long term follow-up. Mean recipient age was 48 years; 63% were
      male and mean body-mass index (BMI) was 23.6; 60.2% had single lung
      transplantation, and mean wait list time was 323 days. Mean AIT totaled 421
      minutes. Graft survival was longer with AIT of 8 to 10 hours compared to 6 to 8
      hours (P = .03). CONCLUSIONS: Donor factor analysis implied only female donor
      status conferred a long-term graft survival advantage. Intracranial pressure rise
      differences appear clinically unimportant. Prolonged cold ischemic time (>10
      hours) or low recipient BMI did not adversely affect allograft function in our
      review.

PMID- 17175366
TI  - Potential renal protective benefits of intra-operative BNP infusion during
      cardiac transplantation.
AB  - BACKGROUND: Recombinant BNP (nesiritide) is known to reduce endothelin levels,
      cause afferent arteriole vasodilation, and increase natriuresis and diuresis. We
      hypothesized that intraoperative infusion of BNP may benefit renal function in
      cardiac transplant patients. METHODS: From June 2003 to September 2005, 22
      consecutive heart transplant patients received BNP at a dose of 0.01
      microg/kg/min before initiation of cardiopulmonary bypass (group A). BNP infusion
      was continued for a mean of 3.3 +/- 1.9 days. Hemodynamics, urine output, and
      serum creatinine levels were prospectively collected and compared with 22
      consecutive patients who underwent heart transplantation between May 2002 and
      June 2003 following the identical transplant protocol, but without BNP infusion
      (group B). RESULTS: At 24 hours postoperatively, mean blood pressure was
      comparable between groups (87 +/- 11 mm Hg vs 89 +/- 17 mm Hg, P = .7), but
      pulmonary artery pressure (18 +/- 5 mm Hg vs 24 +/- 5 mm Hg, P = .001) and
      central venous pressure (12 +/- 5 mm Hg vs 16 +/- 4 mm Hg, P = .01) were lower
      with BNP infusion, whereas cardiac index was augmented (2.8 +/- 0.5 vs 2.4 +/-
      0.6, P = .03). Requirement of low-dose inotropic and vasopressor support was
      equally distributed between groups (P > or = .72). Postoperative urine output for
      the initial 24 hours was higher in group A (84 +/- 15 vs 55 +/- 36 mL/h, P =
      .01). None of the patients with BNP infusion required additional diuretics or
      renal replacement therapy during the first week after transplantation. Mean
      postoperative serum creatinine levels as compared with preoperative values
      remained unchanged within group A (P = .12), but increased significantly in group
      B (P < .001). CONCLUSIONS: Intraoperative BNP infusion in heart transplant
      recipients was associated with favorable postoperative hemodynamics,
      significantly improved urine output, and stable serum creatinine levels. A
      prospective, randomized, multicenter trial is warranted to evaluate the potential
      renal protective benefits of intraoperative BNP infusion in this patient
      population.

PMID- 17175368
TI  - Evaluation of soluble CD30 as an immunologic marker in heart transplant
      recipients.
AB  - CD30 is an immunologic molecule that belongs to the TNF-R superfamily. CD30
      serves as a T-cell signal transducing molecule that is expressed by a subset of
      activated T lymphocytes, CD45RO+ memory T cells. Augmentation of soluble CD30
      during kidney transplant rejection has been reported. Our study sought to
      determine whether the level of sCD30 prior to heart transplant could categorize
      patients into high versus low immunologic risk for a poor outcome. A significant
      correlation was observed between high levels of soluble CD30 and a reduced
      incidence of infection. None of the 35 patients with high pretransplant levels of
      sCD30 level (>90 U/mL) developed infections posttransplantation. However, 9 of 65
      patients who had low levels of sCD30 (<90 U/mL) developed infections
      posttransplantation (P < .02). No remarkable differences were noted among the
      other clinical parameters. The results also showed that the high-definition flow
      bead (HDB) assay detected both weak and strong class I and class II HLA
      antibodies, some of which (weak class II HLA Abs) were undetectable by the anti
      human globulin cytotoxicity method. In addition, more antibody specificities were
      detected by HDB. In conclusion, we have observed that high levels of sCD30 prior
      to heart transplant may be associated with greater immunologic ability and
      therefore produce a protective effect on the development of infection post heart
      transplant. We have also shown that the HDB assay is superior to the visual
      cytotoxicity method to detect HLA antibodies, especially those to class II HLA
      antigens.

PMID- 17175369
TI  - Effect of plasmapheresis for acute humoral rejection after heart transplantation.
AB  - OBJECTIVE: The objective of this study was to report our experience of treating
      acute humoral rejection with plasmapheresis in heart transplant (HT) recipients.
      PATIENTS AND METHODS: From May 1996 to December 2005, 238 HTs were performed
      using therapy with cyclosporine or tacrolimus, azathioprine or mycophenolate
      mofetil, and prednisolone as well as induction treatment with rabbit anti-human
      thymocyte globulin. Endomyocardial biopsy for rejection surveillance was
      performed weekly for the first month, monthly for 3 months, yearly after the
      first year, and whenever rejection was suspected. Immunofluorescence studies with
      IgG, IgM, C3, C4, C1q, and HLA-DR were performed routinely on the first month
      biopsy. After a 2-year trial, immunofluorescence studies were not performed
      routinely, because no significant findings were observed; thus they were
      performed only when clinical deterioration, unstable hemodynamic status, or
      suspicion of rejection occurred on routine echocardiographic examinations.
      Plasmapheresis with fresh frozen plasma exchanging twice the blood volume of the
      patients was performed for 5 days. Rescue immunosuppression with
      methylprednisolone (1 g/d) was delivered for 3 days and the immunosuppressants
      changed, but no intravenous immunoglobulin was prescribed. RESULTS: Twelve
      patients suffered biopsy-proven acute humoral rejection at 3 days to 32 months
      after HT (mean, 9.4 months). Immunofluorescence studies showed positive HLA-DR in
      7 patients; IgG in 4 patients; IgM in 1 patient; C3 in 4 patients; C4 in 1
      patient; and C1q in 1 patient. One patient who was 3 months after HT showed only
      C1q positive but was treated with extracorporeal membrane oxygenation and intra
      aortic balloon pumping support and died 1-month after plasmapheresis. Another
      patient who deteriorated on the 3rd postoperative day and died 3 days after
      plasmapheresis was considered to have vascular rejection by interstitial edema,
      vacuolated endothelial cells and no pathognomonic clinical features, although
      there was no positive immunofluorescence result. All other subjects were
      discharged from the hospital, although 3 required mechanical support during
      plasmapheresis. Hypotension with hypocalcemia was frequently noted during
      plasmapheresis. The 1-year survival rate was 75% +/- 11%, and 5-year survival
      rate, 51% +/- 15%. CONCLUSION: Plasmapheresis with concurrent rescue
      immunosuppression was an effective treatment for acute humoral rejection in HT
      even with unstable hemodynamics.

PMID- 17175370
TI  - T-cell response to staphylococcal enterotoxin B is reduced among heart failure
      patients on ventricular device support.
AB  - Infections are the major complication among patients on left ventricular device
      (LVAD) support. One mechanism that may explain the elevated incidence of
      infection is a deficiency in cellular immunity after LVAD placement. To test this
      hypothesis, we evaluated the in vitro T-cell-proliferative and cytokine response
      following challenge with staphylococcal enterotoxin B in 14 LVAD and 6 non-LVAD
      stable outpatients awaiting heart transplantation. Clinical outcome was followed
      for 12 months. Clinical outcome was poorer (P < .05) for LVAD vs non-LVAD
      patients. T-cell-proliferative response was lower (P = .002) for LVAD vs non-LVAD
      patients. Th1 cytokine expression was lower (P < .05) and Th2 cytokine expression
      was higher (P < .05) for LVAD vs non-LVAD patients. We conclude that LVAD
      recipients are hyporesponsive to superantigen challenge, indicating a depressed
      cellular immunity that may contribute to their increased susceptibility to
      infections.

PMID- 17175371
TI  - Glasgow coma scale 7 or less surveillance program for brain death identification
      in Argentina: Epidemiology and outcome.
AB  - BACKGROUND: In Argentina, the rate of cadaveric organ donation per million
      inhabitants has recently increased to 10.5 (it was previously <7). PURPOSE: To
      overcome this challenge, the National Institute for Organ Donation and
      Transplantation (INCUCAI) created a proactive donor detection plan performed by
      intensive care unit (ICU) physicians (hospital transplantation coordinators) from
      90 selected hospitals across the country. METHODS: A prospective, observational
      study of patients in severe coma status was conducted from September 2003 to
      December 2005. We enrolled hospitalized patients who displayed a Glasgow Coma
      Scale (GCS) of 7 or less and who were admitted to ICUs. Data included
      demographics, etiology of coma, cardiac arrest, brain death, discharge or
      derivation, and positive/negative donation. RESULTS: Among 9841 enrolled
      patients, we excluded 498 who were discharged to another hospital or had unknown
      outcomes, leaving 9343 for analysis including 64% males and 36% females of
      overall mean age 50 +/- 19 years (adults) and 5 +/- 4 years (children). Herein,
      we have highlighted the high risk of death during the first 2 days in the ICU of
      patients with GCS 7 or less. Gunshot to the head-injured patients and those with
      hemorrhagic strokes were less likely to survive. In this study, cardiac arrest
      events and organ donors (OD) GCS 7 or less ratios emerged as quality control
      markers of ICU care, unraveling problems of potential donor maintenance or
      inadequate policies. CONCLUSIONS: The GCS 7 or less surveillance program seemed
      to be a valuable tool for identifying organ donors and potentially treatable
      events, such as the high rate of cardiac arrest observed in this study.

PMID- 17175372
TI  - Transorbital sonographic monitoring of optic nerve diameter in patients with
      severe brain injury.
AB  - OBJECTIVE: We investigated whether alterations in the optic nerve diameter (OND)
      correlated with brain computed tomography (CT) imaging results among patients
      with brain injury and whether monitoring of OND could predict brain death.
      PATIENTS AND METHODS: We enrolled 54 patients with brain injury (Glasgow Coma
      Scale < 8) and 53 controls. OND measurements were performed 3 mm posterior to the
      papillae by means of transorbital sonography. The severity of the injury was
      classified according to a semiquantitative CT neuroimaging scale (1 to 4). All
      patients underwent 3 repeated evaluations of OND combined with synchronous CT
      scans. RESULTS: Twenty-two patients progressed to brain death, while 32 patients
      showed gradual clinical improvement. Upon admission, the patients showed
      significantly increased OND (4.84 +/- 1.2 mm) compared with the controls (3.49 +/
      1.1 mm; P < .001). The median intraobserver variation of OND was 0.2 mm (95%
      confidence intervals [CI]: 0.1-0.7). The median interobserver variation of OND
      was 0.3 mm (95% CI: 0.1-0.9). Alterations in the OND were significantly
      correlated with the neuroimaging scale on 3 repeated evaluations: r = .65, r =
      .70, and r = .73 (all P < .001). An OND greater than 5.9 mm (specificity = 65%
      and sensitivity = 74%; P < .01) and a 2.5 mm increased OND between repeated
      measurements (specificity = 70% and sensitivity = 81%; P < .01) were associated
      with a poor prognosis. CONCLUSIONS: Alterations in OND strongly correlated with
      neuroimaging results among patients with brain injury. However, monitoring of OND
      exhibited a low predictive value for brain death.

PMID- 17175373
TI  - Chromosome abnormalities in advanced stage lymphoblastic lymphoma of children and
      adolescents: a report from CCG-E08.
AB  - Among pediatric non-Hodgkin lymphomas, one of the most frequent types is
      lymphoblastic lymphoma (LBL). Specific chromosome abnormalities are associated
      with prognosis in childhood acute lymphoblastic leukemia, but have not been
      evaluated for prognostic value in pediatric LBL. For the Children's Cancer Group
      protocol CCG-E-08 Etiologic Study of Non-Hodgkin Lymphoma in Childhood, 13
      patients were enrolled with cytogenetic analysis of LBL and on treatment protocol
      CCG-502. Pathology material and karyotypes at initial diagnosis were given
      central review. The patients were aged 6-13 years (median 9 years), with a male
      to-female ratio of 12:1. All patients had advanced disease. Disease relapsed in
      six patients (event-free survival 54% +/- 14%, median 10.8 years). Chromosome
      abnormalities were identified in 11 (85%), and translocations at 14q11.2 likely
      involving the T-cell receptor alpha/delta locus (TCR A/D) occurred in 4 (31%).
      For patients with relapse, four had translocations t(1;14)(p32;q11.2),
      t(8;14)(q24.1;q11.2), t(11;14)(p13;q11.2), or t(9;17)(q34;q23), involving
      breakpoints in the regions of TAL1, MYC, LMO2, and NOTCH1, respectively.
      Pediatric advanced LBLs have a high frequency of chromosome abnormalities; in
      this limited study, these often involved translocations at 14q11.2, the site of
      TCR A/D. Translocations possibly involving TAL1, MYC, LMO2, or NOTCH1 may have
      contributed to poor outcome. Further studies are warranted in larger cohorts of
      children and adolescents with LBL to evaluate the prognostic significance.

PMID- 17175374
TI  - Detection and molecular cytogenetic characterization of a novel ring chromosome
      in a histological variant of Ewing sarcoma.
AB  - Ewing sarcoma/peripheral primitive neuro-ectodermal tumor (PNET) is a round-cell
      sarcoma that may show varying degrees of neuro-ectodermal differentiation. These
      tumors are identified by a characteristic round-cell morphology and
      immunohistochemical profile, as well as by specific translocations involving the
      EWS gene on chromosome 22 and the 3' portion of the E26 transformation-specific
      family of transcription factors. These translocations result in fusion proteins
      that act as aberrant transcription factors. The majority of Ewing sarcoma cases
      are characterized by a balanced t(11;22). Specific chromosomal abnormalities
      often correlate with distinct morphologic or phenotypic subtypes of tumors and
      play an important role in prognosis. Here we describe the molecular cytogenetic
      investigation of a case of Ewing sarcoma in the proximal humerus of a 39-year-old
      male using COBRA (combined binary ratio labelling) fluorescent in situ
      hybridization karyotyping, array comparative genomic hybridization, and EWS-gene
      specific fluorescence in situ hybridization. Multiple chromosomal aberrations
      were identified, including a der(22)r(20;22), resulting in an amplification of
      the proximal region of the EWS gene. This is the first time that both
      translocation and amplification involving the EWS gene and an unidentified gene
      are described. This case adds to the spectrum of both morphology and genetic
      rearrangements in Ewing sarcoma, and shows the importance of combined molecular
      cytogenetic approaches in identifying uncommon rearrangements in sarcomas.

PMID- 17175375
TI  - Evaluation of genetic stability of the SYT gene rearrangement by break-apart FISH
      in primary and xenotransplanted synovial sarcomas.
AB  - Synovial sarcomas (SS) are infrequent and morphologically heterogeneous soft
      tissue sarcomas. The t(X;18)(p11.2;q11.2), which results in fusion of the SYT
      gene at 18q11 with the SSX1, SSX2, or (rarely) SSX4 gene is a primary genetic
      event in 90% of SS. To determine whether the t(X;18) present in the original
      tumor is maintained in its passages, a dual-color break-apart FISH assay for SYT
      gene disruption was performed in two tissue microarrays (TMA) comprising eight
      molecularly confirmed primary SSs and their xenografts, which were followed for
      several generations. A simplified scoring system was applied to the FISH results
      of the primary and xenotransplanted SS to classify the FISH data into distinct
      groups. SYT disruption was identified in all eight primary SS and in all their
      passages without any significant differences among them, despite wide variations
      in xenotransplantation time between the primary tumors and their xenografts. The
      TMA-based FISH assay demonstrated genetic stability related to SYT gene
      rearrangement in primary and xenografted SS.

PMID- 17175376
TI  - No association between dinucleotide repeat polymorphism in intron 1 of the
      epidermal growth factor receptor gene EGFR and risk of lung cancer.
AB  - The tyrosine kinase receptor EGFR pathway is one of the oncogenic signaling
      cascades involved in lung cancer, mediating the epidermal growth factor receptor
      gene EGFR. First-intron polymorphisms with greater numbers of CA dinucleotide
      repeats tend to downregulate EGFR expression, which suggests that this
      polymorphism may modulate susceptibility to lung cancer. The present hospital
      based case-control study evaluated the possible association of CA repeat
      polymorphism in the EGFR gene with risk of lung cancer in a Korean population. A
      bimodal pattern appeared, with a frequency of 57.1% for 20 CA repeats and 18.6%
      for 16 CA repeats. There was, however, no significant difference in distribution
      of allele genotypes between all lung cancer cases and the controls, nor among
      histological types for the cases.

PMID- 17175377
TI  - The 61 A/G EGF polymorphism is functional but is neither a prognostic marker nor
      a risk factor for glioblastoma.
AB  - The A/G61 polymorphism located in the 5'UTR of the EGF gene has been found to be
      both a risk factor and a prognostic factor in glioblastoma (GBM), but the
      functional consequences have not been investigated. Here we show, in vitro, that
      this polymorphism is functional, in that the G allele promoter is 40% more active
      than the A variant (P < 0.001). However, analysis of a large series of 209 GBM
      patients and 214 control subjects did not confirm that A/G61 polymorphism is a
      significant risk factor for GBM, despite a trend for higher GG frequency in these
      patients. Furthermore, A/G61 polymorphism was not a prognostic factor for
      survival in GBM patients, although it does appear to affect progression-free
      survival.

PMID- 17175378
TI  - TSP1 and MMP9 genetic variants in sporadic prostate cancer.
AB  - Angiogenesis plays an important role in the initiation and progression of many
      malignancies including prostate cancer (PCa). Therefore, genes implicated in
      angiogenic pathways could be susceptibility candidate genes for this malignancy.
      In this respect, we investigated the impact of functional genetic variants of
      TSP1 (N700S) and MMP9 (-1562 C/T) genes on the development and progression of
      PCa. This case-control study included 101 PCa patients and 106 healthy controls
      analyzed by polymerase chain reaction -restriction fragment length polymorphism
      assay. No association was observed between any of the TSP1 genotypes and PCa risk
      or severity; however, subjects carrying one copy of the MMP9 T allele exhibited
      threefold higher risk of developing PCa (OR = 2.86; P = 0.004). Regarding
      prognostic value, a significant association was found between the occurrence of
      the MMP9 T allele and the high-grade tumor (OR = 3.21; P = 0.004) and the
      advanced disease (OR = 2.47; P = 0.026). We also analyzed the effect of the
      combined genotypes on PCa risk. The patients with two high-risk genotypes
      exhibited 2.8-fold higher risk of developing PCa than those with only low-risk
      genotypes, but the association was not statistically significant. These findings
      suggest that MMP9 polymorphism is an independent risk factor of PCa development
      and aggressiveness.

PMID- 17175379
TI  - A novel t(3;8)(q27;q24.1) simultaneously involving both the BCL6 and MYC genes in
      a diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphomas (DLBCLs) are a clinically and biologically
      heterogeneous group of hematologic malignancies. Specific genetic aberrations
      underlie some of this heterogeneity. These genetic events include distinct and
      separate translocations resulting in the dysregulated expression of either BCL6
      protein with the t(3;14)(q27;q32) or c-MYC protein with the t(8;14)(q24;q32), as
      a consequence of the juxtaposition of these oncogenes with heterologous promoters
      or enhancers, such as those of the immunoglobulin heavy chain gene. Here, we
      report the case of a patient with DLBCL with a unique t(3;8)(q27;q24.1) that
      involves the BCL6 and MYC genes. We know of no previous report of this
      translocation in DLBCL, which simultaneously affects two key genes implicated in
      lymphomagenesis and may reflect a novel genetic mechanism in neoplastic
      transformation.

PMID- 17175380
TI  - Multipoint interphase FISH in childhood T-acute lymphoblastic leukemia detects
      subpopulations that carry different chromosome 3 aberrations.
AB  - We examined chromosome 3 in 32 childhood acute lymphoblastic leukemia (ALL) bone
      marrow samples. Using interphase multipoint FISH (mp-FISH), which was developed
      by our group, with 42 chromosome 3-specific probes, we detected clonal chromosome
      3 aberrations in 4 T-cell ALL (T-ALL) cases. Four out of seven T-ALL cases
      carried 3q trisomies. One T-ALL case carried either trisomy 3 (in 15% of the
      cells) or a 23-megabase (Mb) 3p13 approximately p12 deletion in a different
      subpopulation of cells of 32%. Another T-ALL case had either 3q trisomy in 11% or
      a 12-Mb 3p12 approximately p13 deletion in 19% of the cells. The deletions were
      overlapping. In both cases, the majority of the bone marrow cells (47 and 70%,
      respectively) were normal chromosome 3 disomics. The interstitial deletions
      detected harbor a known homozygous deletion region between 72.6 and 78.8 Mb,
      which has been described in lung and breast tumors and contains the DUTT1/ROBO1
      tumor suppressor gene. These deletions detected by mp-FISH would have remained
      unnoticed by conventional cytogenetics and multiplex FISH, as well as by current
      methods based on total tumor DNA analysis such as comparative genomic
      hybridization (CGH), array CGH, and loss of heterozygosity (LOH).

PMID- 17175382
TI  - Trisomy 8 as sole cytogenetic abnormality in a case of chronic lymphocytic
      leukemia.
AB  - A 49-year-old man, who had been diagnosed with chronic lymphocytic leukemia (CLL)
      in 2002, had a normal karyotype in his bone marrow. Trisomy 8 was demonstrated in
      his peripheral blood in 2005. Fluorescence in situ hybridization using an LSI CEP
      8 probe performed on the archival bone marrow specimen showed three hybridization
      signals in 40% of 200 interphase cells scored. This confirmed that the trisomy 8
      abnormality was present in both the blood and bone marrow samples. Trisomy 8 as
      the sole chromosomal abnormality in CLL is a very rare finding. The prognostic
      significance of trisomy 8 in CLL remains to be seen.

PMID- 17175381
TI  - Array comparative genomic hybridization reveals unbalanced gain of the MYCN
      region in Wilms tumors.
AB  - Wilms tumor (WT) is one of the most common solid tumors in childhood. It is
      characterized by a nonrandom pattern of chromosomal aberrations whose clinical
      significance is still uncertain. To gain further insight into different genetic
      events and their corresponding biological role, conventional cytogenetics and
      array comparative genomic hybridization (array CGH) were performed on 13 tumor
      samples. In two of these, array CGH revealed, together with other aberrations, a
      low-level amplification and an unbalanced gain in the region of chromosome bands
      2p23 approximately p24 that encompass the MYCN gene. Both events were confirmed
      with a MYCN-specific fluorescence in situ hybridization probe, which showed a
      signal pattern consistent with a small homogenous staining region in one case. In
      addition, mRNA expression levels for MYCN were determined by quantitative reverse
      transcriptase polymerase chain reaction and revealed that gain of chromosomal
      material was reflected in enhanced levels of MYCN mRNA in both tumors, whereby
      also additional tumors showed increased MYCN expression. Therefore, our findings
      suggest that WT is an additional childhood tumor where MYCN gain might play an
      important role in tumor development.

PMID- 17175383
TI  - A novel t(2;3)(p11;q27) in a case of follicular lymphoma.
AB  - Rearrangement of the BCL6 gene is found in follicular lymphomas and in diffuse
      large B cell lymphomas of follicular center cell origin. The breakpoints cluster
      mainly in a region spanning the first noncoding exon of the gene (the major
      breakpoint region). A second breakpoint cluster has also been identified upstream
      of the first BCL6 noncoding exon (the alternative breakpoint region [ABR]). To
      date, eight different rearrangements involving the ABR have been reported. Here,
      we describe a novel rearrangement involving a t(2;3)(p11;q27) translocation that
      affects the ABR in an unusual combination with the IGK locus.

PMID- 17175384
TI  - Translocation (10;17)(p15;q21) is a recurrent anomaly in acute myeloblastic
      leukemia.
AB  - We report here two cases of patients with acute myeloblastic leukemia, type M1
      (FAB classification), associated with a t(10;17)(p15;q21). Fluorescence in situ
      hybridization with the LSI PML/RARA dual-color probe showed the breakpoint to be
      distal to the RARA locus. Four other patients with this translocation have been
      reported, three of them having acute undifferentiated or poorly differentiated
      leukemia.

PMID- 17175385
TI  - A clonal t(8;12)(p11.2;q24.3) as the sole abnormality in a solitary fibrous tumor
      of the pleura.
AB  - A case of solitary fibrous tumor of the pleura with the karyotype
      46,XY,t(8;12)(p11.2;q24.3) is reported. Although rearrangement of 12q15
      approximately 24 is a recurring abnormality in solitary fibrous tumors,
      rearrangement of chromosome 8 was previously unreported in these tumors.

PMID- 17175386
TI  - Tiling resolution array comparative genomic hybridization analysis of a
      fibrosarcoma of bone.
AB  - Fibrosarcoma of bone is a rare malignant tumor accounting for less than 5% of all
      primary malignant bone neoplasms. There is very limited knowledge regarding the
      molecular genetics of this tumor, and there are no cytogenetic data available. In
      the present study, a fibrosarcoma deriving from the left iliac bone of a 10-year
      old girl was characterized using cytogenetics, fluorescence in situ hybridization
      (FISH), and whole genome tiling resolution array comparative genomic
      hybridization (CGH). Cytogenetic and FISH analyses revealed a ring chromosome 6
      as the sole acquired aberration, a finding corroborated by array CGH. The ring
      formation, however, did not result in any gain of genetic material. Nor did the
      breakpoints in 6p25 and 6q14 seem to affect any known gene loci in such a way
      that the ring formation could have resulted in the creation of a fusion gene or
      in the exchange of regulatory sequences. Thus, a reasonable interpretation of the
      pathogenetic significance of the ring formation would be that it resulted in the
      loss of one or more putative tumor suppressor gene loci distal to the two
      breakpoints.

PMID- 17175387
TI  - DNA methylation pattern in 16 tumor-related genes in schwannomas.

PMID- 17175388
TI  - Genetic alterations in a basal cell adenocarcinoma of the glandula
      submandibularis.

PMID- 17175389
TI  - Jumping translocation of 1q in BCR/ABL-positive acute lymphoblastic leukemia.

PMID- 17175390
TI  - Deletion of 3'CBFbeta in an inv(16)(p13.lq22) ascertained by fluorescence in situ
      hybridization and reverse-transcriptase polymerase chain reaction.

PMID- 17175391
TI  - p120-catenin: Past and present.
AB  - p120-catenin was first described in 1989 as a Src substrate whose phosphorylation
      correlated with transformation. It was identified by cDNA cloning in 1992, and
      shown to interact with cadherins in 1994. Though enigmatic for some time, p120
      has emerged as a master regulator of cadherin stability, and an important
      modulator of RhoGTPase activities. With the discovery of p120 family members and
      evidence for fundamental roles in cell biology and cancer, the field has expanded
      dramatically in recent years. As an introduction to this collection of reviews on
      p120 and its relatives, the editors have requested a personal commentary and
      historical perspective on the discovery of p120. The anecdotal parts have no
      particular purpose, but are mostly unpublished and perhaps of interest to some.

PMID- 17175393
TI  - Parental control, parental warmth, and psychosocial adjustment in a sample of
      substance-abusing mothers and their school-aged and adolescent children.
AB  - Parenting interventions for substance-abusing adults have been broadly based on
      two approaches, one emphasizing parental control as a means to managing
      children's behavior and the second emphasizing parental warmth and sensitivity as
      means to fostering children's psychological development. In this investigation,
      we examined associations of parental control and parental warmth, respectively,
      with children's behavioral and psychological adjustment in a sample of 98 women
      enrolled in methadone maintenance and their school-aged and adolescent children.
      Using collateral data collected during the baseline phase of a randomized
      clinical trial (Luthar, S. S., Suchman, N. E., & Altomare, M. [in press].
      Relational Psychotherapy Mothers Group: A randomized clinical trial for substance
      abusing mothers [in preparation]), we tested predictions that (a) parental
      control would be more strongly associated with children's behavioral adjustment
      and (b) parental warmth would be more strongly associated with children's
      psychological adjustment. Both predictions were generally confirmed, although
      some crossover among parenting and child dimensions was also evident. Results
      support the theoretical stance that parental limit setting and autonomy support,
      as well as nurturance and involvement, are important factors, respectively, in
      children's behavioral and psychological adjustment.

PMID- 17175394
TI  - An examination of the Motivational Interviewing Treatment Integrity code.
AB  - This study examines the reliability of the Motivational Interviewing Treatment
      Integrity (MITI) code, a brief scale designed to evaluate the integrity of the
      use of motivational interviewing (MI). Interactions between substance abuse
      counselors with one person role-playing a client were audiotaped and scored by
      trained teams of graduate and undergraduate students. Segments of 10 minutes and
      20 minutes were compared and found to yield the same reliability and integrity
      results. Interrater reliability showed good-to-excellent results for each MITI
      item even with undergraduate raters. Correlations between items showed a coherent
      pattern of interitem correlations. The MITI is a good measure of treatment
      integrity for MI and seems superior to existing measures when indicators of
      client behavior are not needed.

PMID- 17175395
TI  - Mood disorders affect drug treatment success of drug-dependent pregnant women.
AB  - This study examined the impact of co-occurring Axis I disorders on drug treatment
      outcomes of drug-dependent pregnant women. Participants (N = 106) were women who
      met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM
      IV) criteria for opioid dependence and were receiving methadone. Based on DSM-IV
      Axis I criteria, participants were categorized into three groups: (1) absence of
      mood/anxiety disorder (ND, n = 29), (2) primary mood disorder (MD, n = 39), or
      (3) primary anxiety disorder (AD, n = 38). Demographically, the groups were
      similar. The MD group was significantly more likely to be positive for drugs
      while in treatment compared with both the ND and AD groups. The MD and AD groups
      had more psychosocial impairment and higher incidence of suicidal ideation
      compared with the ND group. Interestingly, the AD group spent more days in
      treatment compared with the ND or MD group. These findings highlight the need to
      treat co-occurring Axis I disorders, particularly given the higher relapse risk
      for those with mood disorders.

PMID- 17175396
TI  - Does gender-specific substance abuse treatment for women promote continuity of
      care?
AB  - Research has stressed the value of providing specialized services to women and
      suggests the importance of treatment duration. This quasi-experimental
      retrospective study reports on the continuity of care for women with children who
      were admitted to long-term residential substance abuse treatment. Women were
      admitted to 7 agencies offering specialized, women's only treatment (SP, n = 747)
      or to 9 agencies that provided standard mixed-gender treatment (ST, n = 823).
      Client and treatment data were gathered from administrative sources. We
      hypothesized that women in specialized treatment would demonstrate higher
      continuing care rates after controlling for treatment completion and length of
      stay. Women in SP programs (37%) were more likely than those in ST programs (14%)
      to continue care. Multivariate analyses revealed that SP clients who completed
      treatment with longer stays were most likely to continue care. The findings show
      that specialized treatment for women promotes continuing care and demonstrate the
      importance of treatment completion.

PMID- 17175397
TI  - Psychosocial approaches to psychostimulant dependence: a systematic review.
AB  - This review examines the nature and evidence for the effectiveness of
      psychosocial interventions for psychostimulant dependence. Psychostimulant
      dependence and related harms continue to increase in many parts of the world,
      while treatment responses are predominantly limited to psychosocial
      interventions. The effectiveness of psychosocial interventions is compromised by
      poor rates of treatment induction and retention. As with other substance use
      disorders, increasing the diversity of treatment options is likely to improve
      treatment coverage and outcomes across a broader range of users. Identifying
      medications that might enhance treatment induction and retention would also
      enhance the effectiveness of psychosocial programs. It is concluded that
      psychosocial interventions are moderately effective in reducing psychostimulant
      use and related harms among psychostimulant-dependent persons.

PMID- 17175399
TI  - Risk factors for alcohol and marijuana use among adolescents in foster care.
AB  - This study examined the influences of individual and social risk factors on
      alcohol and marijuana use among a sample of foster care adolescents. Data were
      collected through baseline structured interviews with 320 adolescents (aged 15-18
      years) who resided in foster care placements and participated in a larger
      evaluation study of an independent living program. Approximately 40% of the
      adolescents reported alcohol use, 36% reported marijuana use, and 25% reported
      both alcohol and marijuana use during the 6 months prior to the interview. Final
      logistic regression models indicated that having friends who used marijuana and
      other substances and having skipped school remained most predictive of using
      alcohol, marijuana, or both alcohol and marijuana. Recommendations for substance
      abuse prevention and treatment for these vulnerable adolescents are proposed.

PMID- 17175398
TI  - Attitudes toward the integration of smoking cessation treatment into drug abuse
      clinics.
AB  - This article examines the variables associated with the presence of smoking
      cessation interventions in drug abuse treatment units, as well as staff attitudes
      toward the integration of smoking cessation services as a component of care.
      Surveys were administered to 106 organizations, 348 treatment clinics, and 3,786
      employees in agencies that participated in the National Drug Abuse Treatment
      Clinical Trials Network. Organizational factors, attributes of the treatment
      setting, and staff attitudes toward smoking cessation treatment were assessed.
      Use of smoking cessation interventions was associated with the number of
      additional services offered at clinics, residential detoxification services, and
      attitudes of the staff toward smoking cessation treatment. Staff attitudes toward
      integrating smoking cessation services in drug treatment were influenced by the
      number of pregnant women admitted, the number of ancillary services provided, the
      attitudes of staff toward evidence-based practices, and whether smoking cessation
      treatment was offered as a component of care.

PMID- 17175400
TI  - A pilot study of an interactive web site in the workplace for reducing alcohol
      consumption.
AB  - An interactive web-site-based intervention for reducing alcohol consumption was
      pilot tested. Participants were 145 employees of a work site in the Silicon
      Valley region of California, categorized as low or moderate risk for alcohol
      problems. All participants were given access to a web site that provided feedback
      on their levels of stress and use of coping strategies. Participants randomized
      to the full individualized feedback condition also received individualized
      feedback about their risk for alcohol-related problems. Some evidence was found
      for greater alcohol reduction among participants who received full individualized
      feedback, although due to difficulties in recruiting participants, the sample
      size was inadequate for evaluating treatment effects on drinking. The results
      provide preliminary support for using an interactive web site to provide
      individualized feedback for persons at risk for alcohol problems. However, the
      low participation rate (2.7%) suggests that such an intervention must address the
      challenges of recruiting employees through their work site.

PMID- 17175401
TI  - Children's roles in the social networks of women in substance abuse treatment.
AB  - This study examined the status of children and the types of support available
      from children as reported by women in substance abuse treatment. Findings
      indicate that children are viewed as sources of social support to women on
      treatment. Children were viewed as providing as much sobriety support to
      respondents as that provided by adult network members. In addition, both children
      living with the respondent and children in the care of others were viewed as
      providers of specific types of social support. Implications are drawn for
      practice and research.

PMID- 17175402
TI  - Treatment response by primary drug of abuse: does methamphetamine make a
      difference?
AB  - The purposes of this study were to examine the outcomes of a sample of patients
      receiving publicly funded substance abuse treatment in Washington State and to
      compare the outcomes of those using methamphetamine (MA) with patients using
      other drugs of abuse. All data for this study came from administrative systems in
      Washington State, and the outcomes included completion of and readmission to
      treatment, employment, and various forms of criminal justice involvement.
      Treatment records were linked to outcome data using both deterministic and
      probabilistic matching techniques. Patients were tracked for 1 year following
      their discharge, and analyses were performed separately on a study population of
      adults and a study population of youth. For both adults and youth, the results
      showed that across outcomes, there were few differences between MA users and
      users of other hard drugs, whereas there were consistent differences between MA
      users and users of alcohol and marijuana. Alcohol and marijuana users tended to
      have more positive outcomes than the other groups. Future research should focus
      on more detailed analyses of the type of treatment received by patients,
      particularly for MA users.

PMID- 17175403
TI  - Access to treatment-related and support services in methadone treatment programs.
AB  - This study examines whether the mechanism through which a methadone maintenance
      treatment site offers seven treatment-related and support services is related to
      whether a patient receives such services. Mechanisms include the provision of
      services on-site, at another program site, or through formal or informal linkage
      arrangements. Analysis was conducted on a nationally representative sample of
      methadone treatment sites. Providing services on-site was found to be positively
      related to patient access to a majority of services, whereas, in general,
      offering services at another program site or through formal or informal linkages
      was not found to be effective. Not-for-profit or public ownership of treatment
      sites was also found to be positively related to patient access.

PMID- 17175404
TI  - Stages of change and prenatal alcohol use.
AB  - This study evaluated stage of change as a predictor of alcohol use in a sample of
      301 pregnant women who were either in the precontemplation (62%) or in the action
      (38%) stage of change in their first trimester. Stage of change distinguished
      between different patterns of alcohol consumption before and after pregnancy.
      Those in the precontemplation stage drank more per episode and more often before
      pregnancy than those in the action stage. The precontemplation group also had a
      significantly greater quantity of alcohol after pregnancy. However, stage of
      change did not directly predict subsequent prenatal alcohol use. Previous alcohol
      use, age, and education were the most significant predictors of prenatal drinks
      per drinking day. Temptation to drink alcohol was the best predictor of prenatal
      drinking frequency after study enrollment. Women in both stages of change reduced
      the quantity and the frequency of their alcohol consumption while pregnant and
      achieved comparable rates of abstinence.

PMID- 17175405
TI  - Prevention of depression in children and adolescents.

PMID- 17175406
TI  - Depression in children and adolescents: linking risk research and prevention.
AB  - The National Institute of Mental Health has called for translational research
      linking basic knowledge about vulnerabilities that underlie mood disorders to the
      development of effective preventive interventions. This paper highlights research
      about risk factors for depression in children and adolescents and links it to
      current knowledge about interventions aimed at preventing depression in youth.
      Basic epidemiologic and clinical research indicates that increased risk for
      depression is associated with being female; a family history of depression,
      particularly in a parent; subclinical depressive symptoms; anxiety; stressful
      life events; neurobiological dysregulation; temperament/personality (e.g.,
      neuroticism); negative cognitions; problems in self-regulation and coping; and
      interpersonal dysfunction. These vulnerabilities both increase individuals'
      chances of encountering stress and decrease their ability to deal with the stress
      once it occurs. Although several existing depression-prevention studies have
      targeted one or more of these risk factors, the efficacy of these various
      prevention programs for youth with different combinations of these risk factors
      needs to be investigated further. Most existing depression-prevention programs in
      youth have used cognitive-behavioral techniques, with some success. Other
      depression-prevention strategies have included training in coping, social problem
      solving, social skills, communication skills, and parenting. A comprehensive
      prevention program is recommended that includes multiple intervention components,
      each of which addresses risk and protective factors across different domains and
      levels of analysis.

PMID- 17175407
TI  - Implications of high-risk family studies for prevention of depression.
AB  - The high-risk family study is a powerful design that facilitates identification
      of early forms of expression of depression and premorbid vulnerability, risk, and
      protective factors that are important for defining prevention targets and program
      foci. This paper (1) highlights the strengths of high-risk studies for informing
      early intervention efforts; (2) summarizes findings of familial aggregation from
      controlled high-risk studies of depression; and (3) briefly reviews evidence for
      potential mediators (i.e., early forms of expression, vulnerability factors) that
      explain familial risk and for moderators (i.e., interactive risk and protective
      factors) that enhance or minimize familial risk. New data from the Yale High-Risk
      Study of Comorbidity of Substance Use and Affective Disorders are presented to
      exemplify strategies for identifying specific familial pathways to depression
      among offspring of parents with substance and anxiety disorders. Likewise,
      parental depression is associated with a range of emotional and behavioral
      problems, including anxiety and conduct disorder, in their offspring. These
      nonspecific effects, together with emerging findings on mechanisms of risk,
      support early intervention efforts that target a range of youth at risk for
      depression through multipronged approaches that attend to the individual
      characteristics of the child and parent, clinical comorbidity, and the broader
      family and social context.

PMID- 17175408
TI  - Reducing anxiety to prevent depression.
AB  - Depression is one of the most prevalent mental disorders. Accordingly, treatment
      research has flourished; however, prevention efforts have lagged behind. The
      extant literature is reviewed on the relationship between anxiety and depression
      and the potential for childhood anxiety interventions to reduce the risks of
      secondary depression. Additionally, methodologic issues and recommendations in
      the design of depression prevention programs are presented. Research appears to
      support the view that anxiety plays a role in the development of depression; yet,
      the nature of that role remains unclear.

PMID- 17175409
TI  - Estimating the economic burden of depression in children and adolescents.
AB  - BACKGROUND: Depression in childhood and adolescence creates significant burden to
      individuals, families, and societies by increasing morbidity, increasing
      mortality, and negatively affecting quality of life during times of significantly
      depressed mood. Several studies have estimated the cost of depression in the
      United States and elsewhere, but none have included the costs associated with
      depression in children or younger adolescents. This paper reviews data currently
      available on the cost of depression in childhood and the cost effectiveness of
      interventions to treat and prevent depression in this population. METHODS: A
      systematic review was conducted of published literature related to the cost of
      depression in children and adolescents and of economic evaluations of
      interventions to treat or prevent depression in this population. RESULTS: Five
      articles were identified that included any type of data related to the cost of
      depression in childhood; four articles were identified that conducted economic
      evaluations of interventions to treat or prevent depression in children or
      adolescents. CONCLUSIONS: Little information on the economic burden of depression
      in childhood is currently available. Future research in this area needs to
      include a broad range of costs; long-term outcomes; and costs relevant to
      decision makers in public and private agencies, such as implementation costs and
      costs of sustaining intervention fidelity over time.

PMID- 17175410
TI  - Symptoms of internalizing and externalizing problems: modeling recovery curves
      after the death of a parent.
AB  - BACKGROUND: The death of a parent is a major family disruption that can place
      children at risk for later depression and other mental health problems. DESIGN:
      Theoretically based randomized controlled trial for parentally bereaved children.
      SETTING/PARTICIPANTS: Two-hundred and forty-four children and adolescents and
      their caregivers from 156 families were randomly assigned to the Family
      Bereavement Program (FBP) intervention condition (90 families; 135 children) or
      to a control condition (66 families; 109 children). Data collection occurred from
      1996 to 1998. INTERVENTION: Children and caregivers in the intervention condition
      met separately for 12 two-hour weekly sessions. Skills targeted by the program
      for children included positive coping, stress appraisals, control beliefs, and
      self-esteem. The caregiver program targeted caregiver mental health, life
      stressors, and improved discipline in the home. Both child and caregiver programs
      focused on improved quality of the caregiver-child relationship. MAIN OUTCOME
      MEASURES: Child and caregiver reports of internalizing and externalizing
      symptoms. RESULTS: Longitudinal growth curve modeling was performed to model
      symptoms over time from the point of parental death. The rate of recovery for
      girls in the program condition was significantly different from that of girls in
      the control condition across all outcomes. Boys in both conditions showed reduced
      symptoms over time. CONCLUSIONS: The methodology offers a conceptually unique way
      of assessing recovery in terms of reduced mental health problems over time after
      an event and has contributed to further understanding of FBP intervention
      effects. The intervention program facilitated recovery among girls, who did not
      show reduction in behavior problems without the program, while boys demonstrated
      decreased symptoms even without intervention.

PMID- 17175411
TI  - Links between depression and substance abuse in adolescents: neurobiological
      mechanisms.
AB  - Adolescence is a high-risk period for development of both depressive and
      substance use disorders. These two disorders frequently co-occur in adolescents
      and are associated with significant morbidity and mortality. Given the added
      economic and psychosocial burden associated with the comorbid condition,
      identification of risk factors associated with their co-occurrence is of great
      public health importance. Research with adult animals and humans has indicated
      several common neurobiological systems that link depressive and addictive
      disorders. Given the ongoing maturation of these systems throughout adolescence
      and early adult life, it is not clear how these neurobiological processes
      influence development and progression of both disorders. A better understanding
      of the pathophysiological mechanisms leading to the onset and course of these
      disorders during adolescence will be helpful in developing more effective
      preventive and treatment strategies, and thereby allow these youth to reach their
      full potential as adults.

PMID- 17175412
TI  - Translating research findings on early experience to prevention: animal and human
      evidence on early attachment relationships.
AB  - Recent studies provide a wealth of findings on the mechanisms by which early
      stress exposure, particularly within the early child-parent attachment
      relationship, may influence long-term adaptation. Translating these findings to
      clinical practice and social policy is now underway. In this review, some key
      considerations in this translational task are examined, specifically, the
      conceptual bases underlying the research designs, the putative mechanisms
      involved, and the degree to which currently available findings might shape
      interventions. Although the primary focus is on depression, a broader range of
      phenotypes associated with poor early caregiving environments is also considered.

PMID- 17175413
TI  - Next steps for research on child and adolescent depression prevention.

PMID- 17175414
TI  - Directions for expanding the prevention of depression in children and
      adolescents.

PMID- 17175415
TI  - Contradictions and communication strategies during end-of-life decision making in
      the intensive care unit.
AB  - PURPOSE: The aim of this study was to identify inherent tensions that arose
      during family conferences in the intensive care unit, and the communication
      strategies clinicians used in response. MATERIALS AND METHODS: We identified 51
      clinician-family conferences in the intensive care unit from 4 hospitals in which
      the attending physician believed discussion of withdrawing life-sustaining
      treatments or delivery of bad news would occur. The communication between
      clinicians and family members was analyzed using a dialectic perspective.
      RESULTS: The tension of choosing whether to "let the patient die now" versus to
      "not let the patient die now" was the central contradiction within the
      conferences. Under this overriding theme were 5 categories: killing or allowing
      to die; death as a benefit or a burden; honoring the patient's wishes or
      following the family's wishes; weighing contradictory versions of the patient's
      wishes; and choosing an individual family member as decision maker or the family
      as a unit as decision maker. In response to these contradictions, clinicians used
      2 clusters of communication strategies: decision-centered strategies and
      information-seeking strategies. CONCLUSIONS: This study offered insights into end
      of-life decision making, prompting clinicians to be conscious of the
      contradictions that arise and to use specific strategies to address these
      contradictions in their communication with families.

PMID- 17175416
TI  - Toward learning from patient safety reporting systems.
AB  - PURPOSE: To evaluate the frequency and type of factors involved in incidents
      reported to a patient safety reporting system and answer specific questions to
      enhance the value of PSRS data to improve patient safety. MATERIALS AND METHODS:
      Prospective cohort study of incidents reported from adult and pediatric intensive
      care units (ICUs) in the United States to the web-based, voluntary, and anonymous
      Intensive Care Unit Safety Reporting System. Results from July 1, 2002, to June
      30, 2004. Main outcome variables were incidents that could or did lead to patient
      harm. RESULTS: Analysis includes 2075 incidents from 23 ICUs. Median number of
      reports/ICU/month was 3; 5 hospitals submitted 58% of reports. Harm was reported
      in 42% of incidents with 18 deaths. Common event types: medication/therapeutics
      (42%) and incorrect/incomplete care delivery (20%); 48% of line/tube/drain
      incidents led to physical harm. Deficiencies in training/education contributed to
      49% of incidents and teamwork issues 32%; 42% of incidents had 2 or more
      contributing factors. As the number of contributing factors per incident
      increased, so did risk of harm. CONCLUSIONS: The Intensive Care Unit Safety
      Reporting System provides a mechanism for multiple ICUs to identify hazards. Data
      trends show a correlation between multiple contributing factors and higher rates
      of harm. Further research is needed to help determine how to use PSRS data to
      improve patient safety.

PMID- 17175417
TI  - Management of severe hyperkalemia without hemodialysis: case report and
      literature review.
AB  - PURPOSE: To report a case of severe hyperkalemia successfully managed without the
      use of hemodialysis and to provide a review of the literature regarding the
      management of severe hyperkalemia. METHODS: A clinical case report from the
      medical-surgical intensive care unit of a teaching hospital and a literature
      review are presented. The case involves a 59-year old man with diabetes mellitus,
      essential hypertension, and gout, who presented to hospital with severe
      hyperkalemia (K(+) = 10.4 mEq/L) and normal renal function. He was treated with
      intravenous fluids, sodium bicarbonate, calcium chloride, insulin, calcium
      resonium, and furosemide. RESULTS: The hyperkalemia resolved with conservative
      treatment within 8 hours, and dialytic therapy was not required. The literature
      review supported an initial conservative management approach in stable patients
      with intact renal function. CONCLUSIONS: Hemodialysis is not necessary for all
      cases of severe hyperkalemia and should be reserved for patients with acute or
      chronic renal failure or those with life-threatening hyperkalemia unresponsive to
      more conservative measures.

PMID- 17175418
TI  - Isolation of Aspergillus in critically ill patients: a potential marker of poor
      outcome.
AB  - OBJECTIVE: Recent reports have suggested a rising incidence of pulmonary
      aspergillosis in intensive care unit (ICU) patients. The aim of this study was to
      determine the clinical significance of isolating Aspergillus from respiratory
      samples of critically ill patients. DESIGN: Retrospective review of medical
      records. SETTING: Tertiary medical center that has a large cancer center.
      PATIENTS: All patients admitted to the ICU between January 1998 and August 2004,
      in whom Aspergillus was isolated from respiratory samples or lung tissue.
      INTERVENTION: None. RESULTS: The charts of 104 patients were reviewed.
      Aspergillus was isolated for a mean of 6.6 days after ICU admission. Thirty-three
      percent of patients had hematological malignancy, 10% had absolute neutropenia,
      14% had bone marrow transplant, 11% had HIV infection, and 22% had chronic
      obstructive pulmonary disease. Upon admission to ICU, 79%, 43%, and 19% were on
      antibiotics, corticosteroids, or immunosuppressive therapy, respectively. Ninety
      percent of patients required mechanical ventilation. The mean Acute Physiologic
      and Chronic Health Evaluation II score on ICU admission was 20.6, with predicted
      mortality of 35.5%. However, the actual ICU mortality rate for the cohort was
      50%. Twenty-eight percent of patients were diagnosed with probable or definite
      invasive pulmonary aspergillosis, and 72% had Aspergillus colonization. On
      univariate analysis, the significant clinical differences between the 2 groups
      were the presence of neutropenia (P < .05), immunosuppressants (P < .05),
      antibiotics (P < .05), or bone marrow transplant (P < .05). The differences in
      Acute Physiologic and Chronic Health Evaluation II score, the need for mechanical
      ventilation, ICU length of stay, and ICU mortality were not statistically
      significant. On multivariate analysis, the following factors were independently
      associated with invasive diseases, bone marrow transplantation (P < .01),
      hematological malignancy (P = .02), and broad-spectrum antibiotics (P = .02).
      CONCLUSION: Isolation of Aspergillus in critically ill patients is a poor
      prognostic marker and is associated with high mortality irrespective of invasion
      or colonization. Those who are neutropenic, on immunosuppressive therapy, on
      broad-spectrum antibiotics, or had bone marrow transplantation are more likely to
      have invasive pulmonary aspergillosis.

PMID- 17175419
TI  - Efficacy and safety of intrapulmonary percussive ventilation superimposed on
      conventional ventilation in obese patients with compression atelectasis.
AB  - PURPOSE: To investigate the efficacy and safety of intrapulmonary percussive
      ventilation (IPV) in obese patients, we assessed their respiratory and
      hemodynamic functions during IPV superimposed on conventional ventilation.
      MATERIALS AND METHODS: Ten obese patients with acute respiratory failure due to
      compression atelectasis who had not improved by conventional ventilation were
      treated with IPV. Hemodynamic parameters, ventilator settings, and intracranial
      pressure (n = 1) were recorded every hour. Arterial blood gas was analyzed every
      3 hours. The efficacy and safety of IPV was assessed at the start of weaning.
      RESULTS: Before IPV, Pao(2)/Fio(2) ratio remained low (189 +/- 63 mm Hg), which
      significantly increased to 243 +/- 67 mm Hg at 3 hours from the initiation of IPV
      (P < .01). Furthermore, it continuously increased to 280 +/- 50 mm Hg at 24 hours
      (P < .01). Intrapulmonary percussive ventilation induced significant increase in
      dynamic compliance from control value of 30 +/- 8 mL/cm H(2)O at 0 hours to 35 +/
      9 mL/cm H(2)O at 12 hours (P < .05) and to 38 +/- 8 mL/cm H(2)O at 24 hours (P <
      .01). Heart rate and mean arterial pressure were not significantly changed during
      IPV. Improvement of compression atelectasis was confirmed by their chest computed
      tomographic scans. Adverse effects such as pneumothorax and intracranial
      hypertension were not seen. CONCLUSIONS: These results demonstrated that IPV was
      effective and safe in improving compression atelectasis without adverse effects
      in obese patients.

PMID- 17175420
TI  - Impact of chloride balance in acidosis control: the Stewart approach in
      hemodialysis critically ill patients.
AB  - BACKGROUND: Metabolic acidosis is highly prevalent in critically ill patients
      with acute renal failure. Little is known about the mechanisms by which renal
      replacement therapy intervenes in such cases. The objective of this study is to
      analyze the role of hemodialysis in acidosis correction in intensive care unit
      patients, with an emphasis on chloride levels in plasma and dialysate. METHODS:
      We studied 19 intermittent hemodialysis procedures in 17 acidotic patients. The
      patients were grouped by procedure type (conventional or sustained low-efficiency
      dialysis) and by predialysis plasma chloride level (higher or lower than the
      dialysate chloride concentration). Immediately before and after each procedure,
      blood samples were collected for biochemical analysis. The Stewart method was
      used to calculate the strong ion difference and strong ion gap. RESULTS: The
      patients presented acidosis related to hyperchloremia, hyperphosphatemia, and
      high unmeasured anions. Hypoalbuminemia had an alkalinizing effect. Hemodialysis
      corrected acidosis mainly by reducing phosphate and unmeasured anions. In the
      group as a whole, chloride levels did not change after dialysis. However, when
      analyzed according to predialysis plasma chloride, the high-chloride group
      presented a reduction in plasma chloride, resulting in better base excess
      improvement (Delta standard base excess) than in the low-chloride group. Among
      the determinants of acid-base status, the only factors correlating with Delta SBE
      were Delta strong ion gap and Delta chloride. CONCLUSION: The serum
      chloride/dialysate chloride relationship during hemodialysis has an important
      impact on acidosis control.

PMID- 17175421
TI  - Troponin and septic shock: a reminder.

PMID- 17175422
TI  - Preoperative smoking intervention.

PMID- 17175423
TI  - Improved postoperative analgesia with coadministration of preoperative epidural
      ketamine and midazolam.
AB  - STUDY OBJECTIVE: To assess postoperative pain regulation and pharmacokinetic
      effects of preoperative administration of ketamine and midazolam. DESIGN: Double
      blind, randomized clinical study. SETTING: University hospital. PATIENTS: 46 ASA
      physical status I and II patients (age, 26-58 yrs), scheduled for gastrectomy.
      INTERVENTIONS: Patients were randomly assigned to three treatment groups: a
      preoperative epidural injection of 10 mL (1) ketamine (0.5 mg/kg) solution (Ket
      group); (2) ketamine (0.5 mg/kg) plus midazolam (0.05 mg/kg) solution (KM group);
      or (3) normal saline solution (Ctr group). MEASUREMENTS: Analgesic effects were
      evaluated by Visual Analog Scale (VAS) pain scores at rest, time to first request
      for analgesic (TFA), and morphine consumption during the initial postoperative
      time of 48 hours. Plasma concentration of ketamine in the Ket group and the KM
      group was measured by high-performance liquid chromatography, and the elimination
      half-life of ketamine was calculated. MAIN RESULTS: Compared with the Ctr group,
      the Ket and KM groups had lower VAS pain scores, longer TFA, and lower morphine
      consumption. The KM group had the longest TFA and the lowest morphine consumption
      of the three groups. The KM group also had higher plasma concentrations of
      ketamine 90 to 240 minutes after injection, and a longer elimination half-life of
      ketamine, than did the Ket group. CONCLUSIONS: Preoperative epidural
      coadministration of a low dose of ketamine with midazolam is more effective in
      relieving postoperative pain than using ketamine alone. In addition, epidural
      midazolam prolongs the elimination of ketamine.

PMID- 17175424
TI  - Effects of mannitol in the prevention of lipid peroxidation during liver
      resection with hepatic vascular exclusion.
AB  - STUDY OBJECTIVE: To examine the efficacy of mannitol in the prevention of lipid
      peroxidation during major liver resections performed during hepatic inflow
      occlusion. DESIGN: Prospective, randomized, open-label study. SETTING: Aretaieion
      Hospital, a university-affiliated hospital. PATIENTS: 30 ASA physical status II
      and III patients, less than 75 years of age, scheduled for elective liver
      resection. INTERVENTIONS: All patients received combined general and epidural
      anesthesia. Laparotomy was performed through a bilateral subcostal incision, and
      hepatectomy was performed by inflow vascular exclusion (Pringle's maneuver).
      Before this maneuver, and if the patients were hemodynamically stable, they were
      randomized to receive either mannitol 20% 1.5 mL kg(-1) (group M) or normal
      saline 1.5 mL kg(-1) (group S) intravenously for 30 minutes. MEASUREMENTS: Venous
      blood malondialdehyde (MDA) concentration, as an index of lipid peroxidation, was
      measured spectrophotometrically at selected time points. MAIN RESULTS: Patients
      in both groups presented with raised MDA values (P < 0.05) for the period
      starting before the release of vascular occlusion until 6 days postoperatively.
      In patients receiving mannitol, lower MDA values were observed (P < 0.05)
      compared with group S at the end of operation. CONCLUSION: Mannitol has an
      antioxidant activity, but we were unable to confirm a positive impact on the
      postoperative clinical course.

PMID- 17175425
TI  - The effect of injection of two vs 10 mL saline on the subsequent spread and
      quality of epidural analgesia in parturients.
AB  - OBJECTIVE: To determine whether two vs 10 mL of saline injected into the epidural
      space affects the subsequent spread and quality of epidural analgesia in
      parturients. DESIGN: Randomized, double-blinded, placebo-controlled study.
      SETTING: Delivery room. PATIENTS: 105 ASA physical status I and II parturients
      requesting epidural analgesia. INTERVENTIONS: After identification of the
      epidural space by the loss-of-resistance technique using normal saline, two mL of
      saline was then injected into the epidural space in the 2-mL group (n = 53) and
      10 mL in the 10-mL group (n = 52). Five minutes after the test dose, patients
      received 10 mL of bupivacaine (0.1%) with fentanyl two microg mL(-1).
      MEASUREMENTS: 25 minutes after the initial bolus of bupivacaine and fentanyl,
      spread of block, subsequent pain relief, and influence of the volume of the
      injected saline on the ease of epidural catheter insertion and on the incidence
      of blood vessel trauma and paresthesia were evaluated. RESULTS: The total number
      of dermatomes blocked for cold and pinprick sensation in the 10-mL group was
      significantly more than in the 2-mL group (19 [6-29] vs 15 [4-27] for cold
      sensation, P = 0.000; and 15 [3-29] vs 11.5 [3-26] for pinprick sensation, P =
      0.001). However, the visual analog pain scale and need for supplemental analgesia
      were similar between the two groups. The epidural catheter was easily inserted in
      94.2% of the 2-mL group and 100% of the 10-mL group. The incidence of blood
      vessel trauma was low and the incidence of paresthesia was high without any
      significant difference between the two groups. CONCLUSIONS: 10 mL saline was
      associated with a higher total number of dermatomes blocked for both cold and
      pinprick sensation than the two mL saline. However, the pain relief was adequate
      in both groups, and two mL saline was as effective as the 10 mL in the ease of
      catheter insertion and prevention of intravascular cannulation.

PMID- 17175426
TI  - Use of a nerve stimulator does not improve the efficacy of ultrasound-guided
      supraclavicular nerve blocks.
AB  - OBJECTIVE: To evaluate the efficacy of nerve stimulation as an adjunct to
      ultrasound-guided supraclavicular nerve blocks. DESIGN: Prospective database
      review. SETTING: Tertiary-care medical center. MEASUREMENTS: The records of 94
      consecutive adult patients requiring surgery below the elbow and consenting to
      receive regional anesthesia were studied. The focus of this study was on
      supraclavicular nerve block using ultrasound guidance for nerve identification
      and needle localization. A nerve stimulator with a motor response lower than 0.5
      mA was used for confirmation of findings. An ultrasound image was considered
      adequate if two trunks of the brachial plexus were visualized and if the needle
      was completely seen on the long axis. A successful block was defined as one that
      sufficed as the sole anesthetic without conversion to general anesthesia. Motor
      and sensory examination findings on the upper extremity were also evaluated.
      RESULTS: 74 patients had an adequate ultrasound image. Of the 64 patients with a
      positive motor response, 88% had a successful block, as compared with 90% of the
      10 patients without a motor response (relative risk, 1.09; 95% confidence
      interval, 0.79-1.51; P = 0.52). Neither multivariate correction for baseline
      characteristics nor inclusion of the 20 patients with inadequate ultrasound
      images changed the results. CONCLUSION: For adequately imaged ultrasound-guided
      supraclavicular nerve blocks, a positive motor response to nerve stimulation does
      not increase the success rate of the block. In addition, the high false-negative
      rate suggests that these blocks are usually effective, even in the absence of a
      motor response. Nerve stimulation as an adjunct to ultrasound guidance may have a
      limited role.

PMID- 17175428
TI  - Comparison of buccal and intramuscular dexmedetomidine premedication for
      arthroscopic knee surgery.
AB  - STUDY OBJECTIVE: To compare the sedative, anxiolytic, analgesic, hemodynamic, and
      respiratory effects of buccal dexmedetomidine with intramuscular (IM)
      dexmedetomidine for premedication in patients undergoing arthroscopic knee
      surgery during spinal anesthesia. DESIGN: Randomized, placebo-controlled trial.
      SETTING: University medical center. PATIENTS: 75 ASA physical status I and II
      patients undergoing arthroscopic knee surgery with spinal anesthesia.
      INTERVENTIONS: Patients were randomized to one of three groups for premedication:
      group B, buccal dexmedetomidine 2.5 microg kg(-1); group IM, IM dexmedetomidine
      2.5 microg kg(-1); and group P, buccal 0.9% and NaCl 2 mL. MEASUREMENTS:
      Noninvasive blood pressure, heart rate, respiratory rate, and peripheral oxygen
      saturation were recorded. Sedation and anxiety levels were consecutively assessed
      with Ramsay sedation scores and Visual Analog Scale (VAS) scores of anxiety
      before premedication, before spinal anesthesia, during surgery, and at the end of
      surgery. Two, 4, and 8 hours after surgery, sedation levels, postoperative VAS
      pain scores, and consumption of analgesics (diclofenac sodium) were recorded.
      MAIN RESULTS: Before spinal anesthesia, during surgery, and at the end of
      surgery, sedation and anxiety scores of the patients receiving buccal or IM
      dexmedetomidine were, respectively, higher and lower than in group P. Patients
      receiving buccal dexmedetomidine (group B) had lower requirement of diclofenac
      sodium than group P and lower pain scores than groups P and IM. Mild hypotension
      and bradycardia were observed in the buccal and IM dexmedetomidine patients.
      CONCLUSIONS: Buccal dexmedetomidine for premedication in arthroscopic knee
      surgery provided equal levels of sedation and anxiolysis, and more evident
      analgesia compared with IM dexmedetomidine.

PMID- 17175427
TI  - Does clonidine 50 microg improve cervical plexus block obtained with ropivacaine
      150 mg for carotid endarterectomy? A randomized, double-blinded study.
AB  - STUDY OBJECTIVE: To evaluate the effects of adding 50 microg clonidine to 150 mg
      ropivacaine for superficial cervical plexus block in patients undergoing elective
      carotid endarterectomy (TEA). DESIGN: Randomized, double-blind study. SETTING:
      Departments of Anesthesia and Vascular Surgery of a university hospital.
      PATIENTS: 40 ASA physical status II and III patients undergoing elective TEA
      during superficial cervical plexus block. INTERVENTIONS: Superficial cervical
      plexus block was placed using 20 mL of 0.75% ropivacaine alone (Ropi group, n =
      20) or with the addition of 50 microg clonidine (Ropi-Clonidine group, n = 20).
      If required, analgesic supplementation was given with local infiltration with 1%
      lidocaine and intravenous fentanyl (50-microg boluses). Nerve block profile, need
      for intraoperative analgesic supplementation, and time to first analgesic request
      were recorded. MEASUREMENTS AND MAIN RESULTS: Median (range) onset time was 10
      minutes (5-25 min) in the Ropi group and 5 minutes (5-20 min) in the Ropi
      Clonidine group (P < 0.05). Intraoperative consumption of both 1% lidocaine and
      fentanyl was higher in patients of the Ropi group (15 mL [0-25 mL] and 250 microg
      [50-300 microg]) than in patients of the Ropi-Clonidine group (8 mL [0-20 mL] and
      0 microg [0-150 microg]; P < 0.05 and P < 0.05, respectively). First
      postoperative analgesic request occurred after 17 hours (10-24 hrs) in the Ropi
      group and 20 hours (10-24 hrs) in the Ropi-Clonidine group (P > 0.05).
      CONCLUSIONS: Adding 50 microg clonidine to 150 mg ropivacaine for superficial
      cervical plexus block shortened the onset time and improved the quality of
      surgical anesthesia in patients undergoing elective TEA.

PMID- 17175429
TI  - Correlation of postoperative epidural analgesia on morbidity and mortality after
      colectomy in Medicare patients.
AB  - STUDY OBJECTIVE: To examine, with a large database, the effect of postoperative
      epidural analgesia (vs systemic analgesia) on mortality after colectomy is
      unclear. DESIGN: Retrospective cohort (database) design. SETTING: Medicare
      beneficiaries undergoing elective colectomy. PATIENTS: We examined a cohort of
      12817 patients obtained from a 5% nationally random sample of Medicare
      beneficiaries from 1997 to 2001 who underwent elective partial excision of the
      large intestine. INTERVENTIONS: Patients were divided into two groups depending
      on the presence or absence of billing for postoperative epidural analgesia
      (Current Procedural Terminology code 01996). MEASUREMENTS: The primary outcomes
      assessed were death at 7 and 30 days after the procedure. The rates of major
      morbidity were also compared. Multivariate regression analysis incorporating
      race, gender, age, comorbidities, hospital size, hospital teaching status, and
      hospital technology status was performed to determine whether the presence of
      postoperative epidural analgesia had an independent effect on mortality or major
      morbidity. MAIN RESULTS: Multivariate regression analysis revealed that there was
      no difference between the groups with regard to overall major morbidity; however,
      the presence of epidural analgesia was associated with a significantly lower odds
      of death at 7 days (odds ratio, 0.35; 95% confidence interval, 0.21-0.59; P <
      0.0001) and 30 days (odds ratio, 0.54; 95% confidence interval, 0.42-0.70; P <
      0.0001) after surgery. CONCLUSIONS: The presence of postoperative epidural
      analgesia may decrease the odds of death after elective colectomy; however, the
      mechanism of such a benefit is not clear from our analysis.

PMID- 17175430
TI  - Effects of anesthesia on pain after lower-limb amputation.
AB  - OBJECTIVE: To evaluate the effects of epidural, spinal, and general anesthesia on
      pain after lower-limb amputation. DESIGN: Cross-sectional survey. SETTING:
      Postamputation clinic. PATIENTS: 150 patients who were evaluated one to 24 months
      after their lower-limb amputation. INTERVENTIONS: Patients received epidural,
      spinal, or general anesthesia for their amputation. MEASUREMENTS: Standardized
      questions were used to assess stump pain, phantom sensation, or phantom limb pain
      preoperatively and postoperatively. Pain intensity was assessed on a verbal
      rating scale of 0 to 10. After the interview, each patient's medical history and
      anesthetic record were assessed. RESULTS: Patients who had received epidural
      anesthesia and those who had received spinal anesthesia recalled significantly
      less pain in the week after their surgery (P < 0.05). After an average of 14
      months, there was no difference in stump pain, phantom limb sensation, or phantom
      limb pain between patients who received epidural anesthesia, those who received
      spinal anesthesia, and those who received general anesthesia for their
      amputation. Phantom limb pain continued to be frequent and severe despite
      patients' use of opioid analgesics, amitriptyline, and gabapentin. CONCLUSIONS:
      Patients who received epidural anesthesia and those who received spinal
      anesthesia recalled better analgesia in the first week after their amputation
      than did patients who received general anesthesia. Anesthetic technique had no
      effect on stump pain, phantom limb sensation, or phantom limb pain at 14 months
      after lower-limb amputation.

PMID- 17175431
TI  - Extubation time, hemodynamic stability, and postoperative pain control in
      patients undergoing coronary artery bypass surgery: an evaluation of fentanyl,
      remifentanil, and nonsteroidal antiinflammatory drugs with propofol for
      perioperative and postoperative management.
AB  - STUDY OBJECTIVE: To compare three anesthetic strategies with respect to the time
      of extubation after coronary artery bypass graft (CABG) surgery and to assess
      patient satisfaction with the procedure. DESIGN: Prospective, randomized,
      clinical study. SETTING: Tertiary-care referral center. PARTICIPANTS: 180 cardiac
      surgical patients undergoing primary CABG from January through June 2004.
      INTERVENTIONS: After induction of general anesthesia, patients were allocated to
      one of three groups. All three groups received a continuous infusion of
      intravenous (IV) propofol perioperatively and postoperatively. Group 1 (fentanyl
      infusion group, n = 60) received continuous IV fentanyl infusion perioperatively
      and postoperatively for analgesia. Group 2 (diclofenac group, n = 60) received
      fentanyl bolus doses intraoperatively and diclofenac suppository postoperatively.
      Group 3 (remifentanil group, n = 60) received continuous infusion of IV
      remifentanil perioperatively and IV fentanyl as an immediate postoperative bolus
      followed by continuous fentanyl infusion. Duration of postoperative ventilation
      up to the time of extubation, inotrope requirement, time at which analgesic
      infusion was discontinued, postextubation arterial blood gas analysis, pain
      evaluation via visual analog scale, need for rescue analgesia, awareness during
      surgery, and length of postcardiac surgical unit stay, were evaluated in each
      patient. MAIN RESULTS: The diclofenac group exhibited the shortest time to
      extubation, the least inotrope use, and the fewest rescue doses of analgesic than
      did patients of the other two groups. CONCLUSION: Intravenous propofol with bolus
      doses of IV fentanyl intraoperatively in combination with postoperative
      nonsteroidal antiinflammatory drugs had the best recovery profile in patients
      undergoing primary CABG than did the other two regimens studied.

PMID- 17175433
TI  - Use of lighted stylets to facilitate insertion of double-lumen endobronchial
      tubes in patients with difficult airway anatomy.
AB  - Placement of double-lumen endobronchial tubes (DLTs) into the trachea can be
      difficult because of their size and configuration. For patients with abnormal
      airway anatomy and anticipated difficult tracheal intubation, DLT placement can
      be extremely challenging. We present our experience using lighted stylets to
      facilitate insertion of DLTs in a series of patients with difficult airway
      anatomy.

PMID- 17175434
TI  - Sequential lobar-lung-lobar isolation using a deflecting tip bronchial blocker.
AB  - This case report describes the use of a bronchial blocker (BB) with a wheel
      controlled tip (Cohen flexitip endobronchial blocker) to provide initially middle
      and lower right lobe isolation and then right lung isolation (RLI) during right
      lower lobectomy in a patient with compromised pulmonary function preoperatively.
      As predicted, RLI and one-lung ventilation were associated with worsening
      oxygenation. Toward the end of the surgery, RLI was converted back to middle and
      lower right lobe isolation and oxygenation returned to normal levels. The BB
      design made lobar isolation easier and enabled repositioning of the BB during
      surgery. The techniques used for BB insertion as well as lobar and lung
      separation are described.

PMID- 17175432
TI  - A clinical assessment of the Glidescope videolaryngoscope in nasotracheal
      intubation with general anesthesia.
AB  - STUDY OBJECTIVES: To evaluate the efficacy and safety of the Glidescope
      videolaryngoscope as a device to aid nasotracheal intubation, and to determine
      whether the GSVL provides a better laryngeal view in patients with difficult
      laryngoscopy compared with the Macintosh laryngoscope. DESIGN: Prospective,
      clinical study. SETTING: Two university hospitals. PATIENTS: 156 healthy adult
      ASA physical status I and II undergoing elective plastic and intraoral surgery
      with general anesthesia. INTERVENTIONS: After anesthesia induction with
      intravenous injection of fentanyl 2 microg/kg, propofol 2 mg/kg, and vecuronium
      0.1 mg/kg, nasotracheal intubation was performed using GSVL. MEASUREMENTS:
      Preoperative airway measurements were taken to predict potential difficult
      airways. During nasotracheal intubation using GSVL, laryngeal views, times
      required for full visualization of glottis and successful intubation, difficulty
      encountered and auxiliary maneuvers adopted, and upper airway trauma were
      recorded. The laryngeal views obtained by GSVL and by Macintosh laryngoscope were
      compared. MAIN RESULTS: The laryngeal views obtained by GSVL in all patients were
      Cormack and Lehane (C&L) grades I and II, and the success rate of intubation
      using GSVL at one attempt was 98.1%. The times required for visualization of the
      glottis and successful intubation were 40.2 +/- 11.5 s and 52.7 +/- 12.3 seconds,
      respectively. Patients with C&L grade II needed more auxiliary maneuvers to
      achieve successful intubation than did those with C&L grade I (P < 0.001). In 36
      patients with potential difficult airways, the frequency of difficult
      laryngoscopy (C&L grades III and IV) with the Macintosh laryngoscope (58.3%) was
      significantly higher than with the GSVL (0%, P < 0.05). The frequency of minor
      upper airway trauma was 4.5%. CONCLUSIONS: The GSVL is an effective device for
      nasotracheal intubation and may be incorporated easily into routine clinical
      practice. Compared with the Macintosh laryngoscope, the GSVL can provide an
      improved laryngeal view in the patient with difficult airway.

PMID- 17175435
TI  - Lower limb neuropathy after spinal anesthesia in a patient with latent thiamine
      deficiency.
AB  - We present the case of a 65-year-old man with latent thiamine deficiency who
      manifested lower limb neuropathy after receiving spinal anesthesia. We discuss
      our care of this patient and include a discussion of thiamine deficiency
      generally, its possible origins, symptoms, and recommended techniques for
      treatment of these patients.

PMID- 17175436
TI  - Unusual finding on bronchoscopy: trauma patient identified as a body stuffer.
AB  - We present the case of a trauma patient whose persistently abnormal chest
      radiography led to exploratory bronchoscopy. After the discovery of a foreign
      body in the right lower lobe bronchus, an attempted retrieval resulted in
      accidental perforation of a cocaine bag and release of the drug, which may have
      been the cause of the patient's subsequent pneumonitis.

PMID- 17175437
TI  - Emergency cesarean section in a patient with Fontan circulation using an
      indwelling epidural catheter.
AB  - Management of parturients with a history of Fontan procedure requires careful
      monitoring of cardiovascular parameters and anticipation of potential
      complications. We describe potential pitfalls in a parturient with atriopulmonary
      Fontan circulation, who received epidural analgesia for labor and who later
      required emergency cesarean section. Low-dose local anesthetic in combination
      with meperidine provided excellent perioperative epidural analgesia and
      cardiovascular stability. Epidural analgesia during labor offered optimal pain
      relief and facilitated conversion to surgical anesthesia for an emergency
      cesarean section.

PMID- 17175438
TI  - The anesthesia preoperative assessment: an opportunity for smoking cessation
      intervention.
AB  - Smoking is the single most cause of preventable disease and premature death in
      the United States. We discuss potential hazards that the anesthesiologist should
      be aware of when caring for patients who abuse tobacco. A review of recent
      preoperative smoking cessation initiatives is also provided in addition to
      recommendations on how anesthesiologists may use the preoperative visit as an
      opportunity to play a more active role in reducing the burden of tobacco-related
      disease.

PMID- 17175439
TI  - Takotsubo vs myocardial infarction--a new anesthetic dilemma?

PMID- 17175441
TI  - Insect microRNAs: Structure, function and evolution.
AB  - The small regulatory non-coding RNA molecules, known as microRNAs, have been
      recognized as potential regulator(s) of gene expression at the post
      transcriptional level. In Drosophila melanogaster, microRNAs have been identified
      that control important developmental processes such as apoptosis, cell division,
      Notch signaling, neural development and oogenesis, among others. Once activated
      through a step-wise maturation process, a microRNA can potentially regulate more
      than 50 target genes temporally and spatially in Drosophila. Thus, it is of
      tremendous importance to understand how these small RNA molecules have evolved
      and how they are expressed and regulated to impact cellular function and the
      associated evolutionary fitness. Studies of microRNAs in diverse insect species
      using the genome sequences (at least 49 insect genome sequences are in progress)
      may provide important clues to better understand the natural selection of
      microRNA genes in particular and their impact on biological functions in insects
      in general.

PMID- 17175442
TI  - The cyanogenic glucoside composition of Zygaena filipendulae (Lepidoptera:
      Zygaenidae) as effected by feeding on wild-type and transgenic lotus populations
      with variable cyanogenic glucoside profiles.
AB  - Zygaena larvae sequester the cyanogenic glucosides linamarin and lotaustralin
      from their food plants (Fabaceae) as well as carry out de novo biosynthesis of
      these compounds. In this study, Zygaena filipendulae were reared on wild-type
      Lotus corniculatus and wild-type and transgenic L. japonicus plants with
      differing content and ratios of the cyanogenic glucosides linamarin and
      lotaustralin and of the cyanoalkenyl glucosides rhodiocyanoside A and D. LC-MS
      analyses, free choice feeding experiments and developmental studies were used to
      examine the effect of varying content and ratios of these secondary metabolites
      on the feeding preferences, growth and development of Z. filipendulae. Larvae
      reared on cyanogenic L. corniculatus developed faster compared to larvae reared
      on L. japonicus although free choice feeding trials demonstrated that the latter
      plant source was the preferred food plant. Larvae reared on acyanogenic L.
      corniculatus showed decelerated development. Analysis of different life stages
      and tissues demonstrate that Z. filipendulae strive to maintain certain threshold
      content and ratios of cyanogenic glucosides regardless of the composition of the
      food plants. Despite this, the ratios of cyanogenic glucosides in Z. filipendulae
      remain partly affected by the ratio of the food plant due to the high proportion
      of sequestering that takes place.

PMID- 17175443
TI  - Chemosensory proteins in the honey bee: Insights from the annotated genome,
      comparative analyses and expressional profiling.
AB  - Small chemosensory proteins (CSPs) belong to a conserved, but poorly understood
      protein family that has been implicated in transporting chemical stimuli within
      insect sensilla. However, their expression patterns suggest that these molecules
      are also critical for other functions including early development. Here we used
      both bioinformatics and experimental approaches to characterize the CSP gene
      family in a social insect, the Western honey bee Apis mellifera, and then
      compared its members to CSPs in other arthropods. The number of CSPs in the honey
      bee genome (six) is similar to that found in the sequenced dipteran species (four
      seven), but is much lower than the number of CSPs in the moth or in the beetle
      (around 20 each). These differences seem to be the result of lineage specific
      expansions. Our analysis of CSPs in a number of arthropods reveals a conserved
      gene family found in both Mandibulates and Chelicerates. Expressional profiling
      in diverse tissues and throughout development reveals broader than expected
      patterns of expression with none of the CSPs restricted to the antennae and one
      found only in the queen ovaries and in embryos. We conclude that CSPs are
      multifunctional context-dependent proteins involved in diverse cellular processes
      ranging from embryonic development to chemosensory signal transduction. Some CSPs
      may function in cuticle synthesis, consistent with their evolutionary origins in
      the arthropods.

PMID- 17175444
TI  - Prenyltransferase of larval and adult M. sexta corpora allata.
AB  - Prenyltransferase activity derived from the corpora allata (CA) of the
      lepidopteran insect, Manduca sexta, has been characterized. The coupling of
      allylic substrates DMAPP and GPP with the non-allylic substrate IPP was evaluated
      using CA homogenates of both the larval and adult stages of development. The
      effect of additives and inhibitors, assay conditions, and metal preference were
      examined. The cellular location of prenyltransferase activity was also
      investigated. We found subtle differences between larval and adult preparations,
      including metal and detergent preference, and while larval prenyltransferase
      activity was strictly cytosolic, prenyltransferase derived from adult CA was
      found in both the cytosolic and pellet fractions. Differences in kinetics as a
      function of development were also noted. When GPP was utilized as allylic
      substrate, adult prenyltransferase displayed cooperative behavior; while with
      DMAPP, biphasic kinetics were observed. In fifth instar larvae, prenyltransferase
      activity was highest on days 1-2 and reaction end products changed as a result of
      insect age. Taken together, these results suggest that larval and adult
      prenyltransferase of M. sexta have distinct enzymological properties and that the
      adult CA possess more than one prenyltransferase.

PMID- 17175445
TI  - A new amino-acid substitution in acetylcholinesterase 1 confers insecticide
      resistance to Culex pipiens mosquitoes from Cyprus.
AB  - In insects, selection of insecticide-insensitive acetylcholinesterase (AChE) is a
      very common resistance mechanism. Mosquitoes possess both AChE1 and AChE2 enzymes
      and insensitivity is conferred by single amino-acid changes located near the
      active site of the synaptic AChE1. Only two positions have been reported so far
      to be involved in resistance, suggesting a very high structural constraint of the
      AChE1 enzyme. In particular, the G119S substitution was selected in several
      mosquitoes' species and is now largely spread worldwide. Yet, a different type of
      AChE1 insensitivity was described 10 years ago in a Culex pipiens population
      collected in Cyprus in 1987 and fixed thereafter as the ACE-R strain. We report
      here the complete amino-acid sequence of the ACE-R AChE1 and show that resistance
      is associated with a single Phe-to-Val substitution of residue 290, which also
      lines the active site. Comparison of AChE1 activities of the recombinant F290V
      protein and ACE-R mosquito extracts confirmed the causal role of the substitution
      in insensitivity. Biochemical characteristics of the mutated protein indicated
      that the resistance level varies with the insecticide used. A molecular diagnosis
      test was designed to detect this mutation and was used to show that it is still
      present in Cyprus Island.

PMID- 17175446
TI  - Transcriptome analysis of the salivary glands of Dermacentor andersoni Stiles
      (Acari: Ixodidae).
AB  - Amongst blood-feeding arthropods, ticks of the family Ixodidae (hard ticks) are
      vectors and reservoirs of a greater variety of infectious agents than any other
      ectoparasite. Salivary glands of ixodid ticks secrete a large number of
      pharmacologically active molecules that not only facilitate feeding but also
      promote establishment of infectious agents. Genomic, proteomic and immunologic
      characterization of bioactive salivary gland molecules are, therefore, important
      as they offer new insights into molecular events occurring at the tick-host
      interface and they have implications for development of novel control strategies.
      The present work uses complementary DNA (cDNA) sequence analysis to identify
      salivary gland transcripts expressed by the Rocky Mountain wood tick, Dermacentor
      andersoni, a vector of the human pathogens causing Rocky Mountain spotted fever,
      Colorado tick fever, tularemia, and Powassan encephalitis as well as the
      veterinary pathogen Anaplasma marginale. Dermacentor andersoni is also capable of
      inducing tick paralysis. Automated single-pass DNA sequencing was conducted on
      1440 randomly selected cDNA clones from the salivary glands of adult female D.
      andersoni collected during the early stages of feeding (18-24h). Analysis of the
      expressed sequence tags (ESTs) resulted in 544 singletons and 218 clusters with
      more than one quality read and attempts were made to assign putative functions to
      tick genes based on amino acid identity to published protein databases.
      Approximately 25.6% (195) of the sequences showed limited or no homology to
      previously identified gene products. A number of novel sequences were identified
      which presented significant sequence similarity to mammalian genes normally
      associated with extracellular matrix (ECM), regulation of immune responses, tumor
      suppression, and wound healing. Several coding sequences possessed various
      degrees of homology to previously described proteins from other tick species.
      Preliminary nucleotide variation analysis of these and other tick sequences
      suggests extensive nucleotide diversity, which has implications for evolution of
      tick feeding. Intra-species diversity studies can be a promising tool for
      identifying sequence variations potentially associated with phenotypic traits
      affecting vector-host-pathogen interactions.

PMID- 17175447
TI  - A soluble beta-cyanoalanine synthase from the gut of the variegated grasshopper
      Zonocerus variegatus (L.).
AB  - Beta-cyanoalanine synthase (beta-cyano-l-alanine synthase; l-cysteine: hydrogen
      sulphide lyase (adding hydrogen cyanide (HCN)); EC 4. 4.1.9) was purified from
      the cytosolic fraction of the gut of grasshopper Zonocerus variegatus (L.) by ion
      exchange chromatography on DEAE-Cellulose and gel filtration on Sephadex G-100
      columns. The crude enzyme had a specific activity of 2.16nmol H2S/min/mg. A
      purified enzyme with a specific activity, which was seventeen times higher than
      that of the crude extract, was obtained. A molecular weight of about 55.23+/
      1.00Kd was estimated from its elution volume on Sephadex G-100. The fraction when
      subjected to sodium dodecyl sulphate-polyacrylamide elel electrophoresis revealed
      the presence of a protein band with Mr of 23.25+/-0.25Kd. The enzyme exhibited
      Michaelis-Menten kinetics having Km of 0.38mM for l-cysteine and Km of 6.25mM for
      cyanide. The optimum temperature and pH for activity were determined to be at 30
      degrees C and pH 9.0, respectively. This enzyme might be responsible for the
      ability to detoxify cyanide in this insect pest and hence its tolerance of the
      cyanogenic cassava plant. Biophysical, biochemical and kinetic properties of this
      enzyme, which will reveal how this ability can possibly be compromised by enzyme
      inhibition, may lead, in the long term, to the potential use of this enzyme as
      drug target for pest control.

PMID- 17175448
TI  - Absolute configuration of the creatonotines and callimorphines, two classes of
      arctiid-specific pyrrolizidine alkaloids.
AB  - Arctiids which as larvae sequester pyrrolizidine alkaloids (PAs) from their food
      plants are known to synthesize insect-specific PAs by esterifying necine bases
      derived from plant PAs with necic acids of insect origin. There are two classes
      of insect PAs, the creatonotines and the callimorphines. The creatonotines
      contain as necic acids either 2-hydroxy-3-methylbutyric acid (creatonotine A) or
      2-hydroxy-3-methylpentanoic acid (creatonotine B). The three known callimorphines
      contain 2-hydroxy-2-methylbutanoic acid whose hydroxyl group can be either free
      (deacetylcallimorphine) or acetylated (callimorphine) or propionylated
      (homocallimorphine). Insect PAs are assumed to play an important role in the
      recycling of plant derived necine bases and the processing by trans
      esterification of PA monoesters that cannot be directly transmitted to the
      insect's pupal and adult life-stages. The absolute configuration of the insect
      specific necic acids was elucidated in the context of the suggested role of the
      insect PAs as insect-made mimics of plant monoester PAs of the lycopsamine type.
      For this purpose all needed stereoisomers were synthesized and a gas
      chromatography-mass spectrometry (GC-MS) method was established that allows the
      enantioselective separation and assignment of the stereochemistry of all insect
      specific necic acids as their methyl esters. The method could also be applied to
      the GC-MS analysis of the intact alkaloids which were hydrolyzed during injection
      and converted into their methyl esters. Analysis of the creatonotines and
      callimorphines isolated from the polyphagous arctiids Estigmene acrea and Grammia
      geneura that were fed with pure PAs and defined PA mixtures revealed the
      following absolute configuration: the callimorphines and creatonotine A were
      present in 2'R configuration, whereas creatonotine B was found as mixture of
      (2'R, 3'S)- and (2'S, 3'S)-stereoisomers. The ratio of 2'S to 2'R was extremely
      variable ranging from 98% S to 94% R. The cause of the lack of stereospecificity
      is discussed particularly in respect of a possible epimerization of the hydroxyl
      group at C-2' in analogy to the known epimerization at C-3' of plant acquired PAs
      of the lycopsamine type.

PMID- 17175449
TI  - Biochemical and molecular characterization of allatotropin and allatostatin from
      the Eri silkworm, Samia cynthia ricini.
AB  - In a previous study, allatotropic and allatostatic activities were observed in
      brain extract from the Eri silkworm, Samia cynthia ricini (Samcri) [Li, S.,
      Jiang, R.-J., Cao, M.-X., 2002b. Allatotropic and allatostatic activities in
      brain extracts of the Eri silkworm, S. cynthia ricini, and the effects of Manduca
      sexta allatotropin and M. sexta allatostatin on juvenile hormone in vitro.
      Physiol. Entomol. 27, 322-329]. In the present study, the HPLC purified Samcri
      allatotropin (AT) and -allatostatin (AST) factors were shown to have the same
      retention time as those of M. sexta (Manse)-AT and -AST, respectively. Moreover,
      the amino acid sequences of mature Samcri-AT and -AST deduced from their encoding
      cDNAs are identical to the Manse-AT and -AST amino acid sequences. Both Samcri-AT
      and -AST genes were expressed in brain, nerve cord, and midgut, with Samcri-AT
      also detected in gonads and epidermis, suggesting their pleiotropic physiological
      functions. The expression levels of Samcri-AT and -AST genes correlated well with
      the allatoregulatory activities during the period of adult emergence indicating
      the two peptides tightly control JH synthesis, in a contradictive and cooperative
      manner. Our biochemical and molecular data of Samcri-AT and -AST and other
      studies demonstrate that these two peptides regulate JH synthesis by corpora
      allata in Lepidoptera and have pleiotropic physiological effects.

PMID- 17175450
TI  - Patterns of failure and survival for nonoperative treatment of stage c0 distal
      rectal cancer following neoadjuvant chemoradiation therapy.
AB  - Neoadjuvant chemoradiation therapy (CRT) is the preferred treatment option for
      distal rectal cancer. Complete pathological response after CRT has led to the
      proposal of nonoperative approach as an alternative treatment for highly selected
      patients with complete clinical response. However, patterns of failure following
      this strategy remains undetermined. Three hundred sixty-one patients with distal
      rectal cancer were managed by neoadjuvant CRT including 5-FU, leucovorin, and
      5040 cGy. Tumor response assessment was performed at 8 weeks following CRT.
      Patients with complete clinical response were not immediately operated on and
      were closely followed. One hundred twenty-two patients were considered to have
      complete clinical response after the first tumor response assessment. Of these,
      only 99 patients sustained complete clinical response for at least 12 months and
      were considered stage c0 (27.4%) and managed nonoperatively. Mean follow-up was
      59.9 months. There were 13 (13.1%) recurrences: 5 (5%) endorectal, 7 (7.1%)
      systemic, and 1 (1%) combined recurrence. All 5 isolated endorectal recurrences
      were salvaged. Mean recurrence interval was 52 months for local failure and 29.5
      months for systemic failure. There were five cancer-related deaths after systemic
      recurrences. Overall and disease-free 5-year survivals were 93% and 85%. Even
      though surgery remains the standard treatment for rectal cancer, nonoperative
      treatment after complete clinical response following neoadjuvant CRT may be safe
      and associated with good survival rates in a highly selected group of patients.
      Survival in these patients is significantly affected by systemic failure.
      Exclusive local failure occurs late after CRT completion and is frequently
      amenable to salvage therapy.

PMID- 17175451
TI  - Ileorectal anastomosis for slow transit constipation: long-term functional and
      quality of life results.
AB  - The results of colectomy and ileorectal anastomosis (IRA) in patients diagnosed
      by physiologic testing as having slow transit constipation (STC) have been
      reported. The durability of functional results and long-term quality of life
      (QoL) in these patients, however, has not been established. Between 1987 and
      2002, 3670 patients were evaluated for constipation at our institution; 110 (3%)
      fulfilled the criteria for STC and underwent an IRA. Patients were prospectively
      followed and functional outcomes assessed annually by standardized
      questionnaires. After a median follow-up of 11 years, 104 eligible patients were
      mailed validated questionnaires to assess functional outcomes and QoL (Knowles
      Eccersley-Scott Symptom [KESS] score, the Irritable Bowel Syndrome Quality of
      Life [IBS-QOL], and the SF-12 health survey). Prospectively assessed functional
      data was available on 85 of 104 (82%) eligible patients. At last follow-up,
      improvement of constipation and satisfaction with bowel function was reported by
      98% and 85% of patients, respectively. Performance measures including social
      activity, household work, sexual life, and family relationships were reported to
      have improved or were not affected as a result of surgery by 75%, 86%, 81%, and
      86% of the patients respectively. Fifty-nine patients (57%) responded to the
      study questionnaires. All 59 patients reported their constipation to be better
      since IRA, 83% did not require any medication, and 85% reported being satisfied
      with bowel function. The KESS scores of patients undergoing IRA for STC (median
      6, range 0-35) were lower than reported scores of STC patients not operated upon
      (median 21, range 11-35, P<0.001) indicating symptomatic improvement after
      surgery. Mean IBS-QOL scores were similar to reported scores of patients
      undergoing IRA for other conditions [80 (23) versus 84 (16)], P=0.7). Mean SF-12
      physical and mental summary scores were similar to reported SF-12 scores of the
      normal population (49.5 versus 50 and P=0.70, 48.7 versus 50, P=0.42,
      respectively). Ileorectal anastomosis in appropriately selected patients with
      slow transit constipation results in durable symptomatic relief and a long-term
      quality of life indistinguishable from the general population.

PMID- 17175452
TI  - A margin-negative R0 resection accomplished with minimal postoperative
      complications is the surgeon's contribution to long-term survival in pancreatic
      cancer.
AB  - Pancreatic cancer has a poor prognosis with complete surgical resection being the
      only therapy to offer a realistic chance for long-term survival. The aim of this
      study is to identify surgery-related variables that influence long-term survival.
      Between 1990 and 2002, 226 consecutive patients (mean age of 64+/-11 years) had
      resection for pancreatic adenocarcinoma. Prognostic variables in these patients
      were analyzed using univariate and multivariate analysis. Two hundred four
      patients (90%) had pancreaticoduodenectomy, 13 patients (6%) had distal
      pancreatectomy, and 9 patients (4%) had a TP. Stage I disease was present in 50
      (22%), stage II disease in 170 (75%), and stage III disease in 6 (3%). R0
      resections were achieved in 70%. Operative morbidity was 36% and 30-day mortality
      was 6%. Actual 1-year, 3-year, and 5-year survival rates were 49% (n=111), 14%
      (n=31), and 4% (n=9). Using multivariate analysis: tumor size, tumor
      differentiation, obtaining an R0 resection, and lack of postoperative
      complications were variables associated with long-term survival. Long-term
      survival in patients with pancreatic cancer after resection remains poor.
      Achieving a margin negative resection (R0) with no postoperative complications
      are prognostic variables that can be affected by the surgeon.

PMID- 17175453
TI  - The influence of positive peritoneal cytology on survival in patients with
      pancreatic adenocarcinoma.
AB  - The American Joint Committee on Cancer (AJCC) staging system for pancreatic
      adenocarcinoma classifies positive peritoneal cytology as stage IV disease. Data
      are limited with respect to the prevalence of positive peritoneal cytology and
      its influence on survival in patients with resectable, locally advanced, and
      metastatic disease. Four hundred sixty-two patients underwent staging laparoscopy
      for pancreatic adenocarcinoma between January 1995 and December 2005. Kaplan
      Meier survival comparisons were performed to evaluate the significance of
      positive peritoneal cytology on overall survival (OS) in resected patients and
      patients with locally advanced and metastatic disease. Of the 462 patients, 47%
      (217/462) underwent a pancreatic resection. The 21% (95/462) with locally
      advanced disease and 32% (150/462) with metastatic disease did not undergo
      resection. Peritoneal cytology was positive in 17% (77/462), and was associated
      with stage of disease (metastatic, 37%; locally advanced, 11%; resected, 5%;
      P=0.01). Positive cytology was not associated with OS in patients with metastatic
      disease or locally advanced disease, but was in resected patients (median, 16
      months vs. 8 months; P<0.001). Node-positive disease was present in 8 of 10
      patients resected with positive cytology (2 years OS, 12% positive cytology vs.
      23% negative; P=0.006). In this study, patients who underwent resection in the
      presence of positive peritoneal cytology and absence of other identifiable
      metastatic disease had a similar survival as other patients with stage IV
      disease.

PMID- 17175454
TI  - The utility of F-18 fluorodeoxyglucose whole body PET imaging for determining
      malignancy in cystic lesions of the pancreas.
AB  - Previous studies have suggested that whole body positron-emission tomography
      (PET) can distinguish between benign and malignant cysts of the pancreas.
      Patients were identified (n = 68) who had undergone whole body PET imaging for a
      cystic lesion of the pancreas between Jan. 1997 and May 2005. Cross-sectional
      imaging studies were reviewed by a single blinded radiologist, and positive PET
      studies were reviewed by a blinded nuclear medicine physician. Operative
      resection was performed in 21 patients (31%), and 47 patients were managed with
      radiographic follow-up. F-18 Fluorodeoxyglucose (FDG)-avid lesions were
      identified in eight of the 68 patients (12%). Within the resected group of
      patients (n=21), four of the seven patients (57%) with either in situ or invasive
      malignancy (adenocarcinoma: 3 of 5, papillary mucinous carcinoma: 1 of 2) had
      positive PET imaging (mean SUV, 5.9; range 2.5-8.0), and 2 of the 14 patients
      (14%) with benign lesions had positive PET imaging (serous cystadenoma, n=1,
      SUV=3.3; pseudocyst n=1, SUV=2.7). All lesions proven to be malignant with
      increased FDG uptake had highly suspicious findings on cross-sectional imaging.
      Within the group of resected patients, the sensitivity of PET for identifying
      malignant pathology was 57%, and the specificity was 85%. The sensitivity and
      specificity of PET for malignancy in this study was lower than previously
      reported, and PET findings did not identify otherwise occult malignant cysts. We
      do not believe whole body FDG-PET to be essential in the evaluation of cystic
      lesions of the pancreas.

PMID- 17175455
TI  - Cytoreduction results in high perioperative mortality and decreased survival in
      patients undergoing pancreatectomy for neuroendocrine tumors of the pancreas.
AB  - We reviewed our experience with pancreatectomy for neuroendocrine tumors (NE) to
      determine outcomes after R0/R1 or R2 resection and compare them to patients in
      whom resection was not attempted. Data were reviewed for all patients presenting
      with NE tumors of the pancreas between 1990 and 2005. Kaplan-Meier survival
      curves were compared by log-rank analysis. Multivariate analysis was completed
      using Cox proportional hazards to identify risk factors for poor survival after
      resection. Of 120 patients, 65 (54%) had functional tumors. Resection was
      undertaken in 83: distal pancreatectomy in 41, pancreaticoduodenectomy in 27,
      enucleation in 14, and central pancreatectomy in 1. Survival was significantly
      longer after resection (91 months versus 24, P<0.001). R0/R1 resection was
      accomplished in 64 (77%) and resulted in lower perioperative mortality (2% versus
      21%, P<0.01) and longer survival (112 months versus 24, P<0.001) compared to R2
      resection. Survival after R2 resection was no better than after no resection.
      Factors predictive of decreased survival were moderate/poor differentiation, R2
      resection, and high-risk features. Long-term survival is possible following
      complete resection for NE tumors of the pancreas. However, cytoreduction
      resulting in incomplete tumor removal carries significant perioperative mortality
      without long-term survival benefit and should be discouraged.

PMID- 17175456
TI  - Durability of portal venous reconstruction following resection during
      pancreaticoduodenectomy.
AB  - Venous resection and reconstruction is becoming more common during
      pancreaticoduodenectomy (PD). There are multiple options for reconstruction of
      the mesenteric venous system ranging from primary repair to grafting with
      autologous or synthetic material. Few studies report on the patency rates and
      long-term morbidity of these repairs. We sought to describe our experience with
      venous reconstruction during PD with specific attention to patency and long-term
      morbidity and mortality. Thrombosis rates of mesenteric venous reconstruction
      during PD are low, with low associated morbidity. In this retrospective cohort,
      clinical, operative, and pathologic data were collected from consecutive patients
      for 1988 through 2003. Graft patency on follow-up imaging studies was determined,
      and short- as well as long-term morbidity and mortality were recorded. Sixty-four
      patients underwent PD with venous resection/reconstruction from 1988 through
      2003. Mean patient age was 63 years, with pancreatic ductal adenocarcinoma as the
      pathology in 88%. Reconstruction consisted of primary lateral venorrhaphy in 29
      (45%), PTFE graft in 18 (28%), primary end-to-end repair in 13 (20%), and
      autologous vein graft in 4 (6%). There was one perioperative death (2%). Follow
      up imaging to assess patency was available for a mean of 12.2 months
      postoperatively. Eleven thromboses were diagnosed at a mean of 11.9 months. Three
      thromboses (5%) were noted within 30 days and full anticoagulation was chosen.
      Fifty-three percent of patients received anticoagulation with aspirin, warfarin,
      or clopidogrel based upon surgeon preference. There was no difference in
      thrombosis rates between those receiving anticoagulation and those who did not
      (P=0.65). In those patients with thrombosis outside the acute time period,
      morbidity was limited to ascites in three patients and splenic vein thrombosis
      with uncomplicated esophageal varices in another patient. Mesenteric venous
      resection and reconstruction during PD has a high patency rate, and those
      reconstructions that do thrombose are associated with a low morbidity. The
      majority of reconstruction thromboses that occurred late were associated with
      recurrence.

PMID- 17175457
TI  - In vitro evidence for role of ERK, p38, and JNK in exocrine pancreatic cytokine
      production.
AB  - Elucidation of mechanisms of acinar cell cytokine production is essential for a
      better understanding of acute pancreatitis pathogenesis. We hypothesize that the
      stress kinases ERK, p38, and JNK play an important role in acinar cell cytokine
      production. Rat pancreatic fragments were incubated with 100 nM concentration of
      the cholecystokinin analog caerulein or 100 nM caerulein and specific ERK
      inhibitor (100 microM PD98059), specific p38 inhibitor (10 microM SB203580), or
      specific JNK inhibitor (20 microM SP600125). After 3 hours of caerulein
      treatment, pancreatic fragments were homogenized and assayed for total and
      phosphorylated ERK, p38, and JNK, and for tumor necrosis factor-alpha or
      interleukin-1beta concentrations (ELISA). Pancreatic fragments stimulated with
      caerulein showed activation of ERK, p38, and JNK and increased cytokine
      concentrations (ANOVA, P<0.05). Specific stress kinase inhibitors significantly
      attenuated caerulein-induced activation of the corresponding stress kinase and
      cytokine production; however, the effect of the JNK inhibitor was comparatively
      less convincing. Increased activation of ERK, p38, and JNK in pancreatic
      fragments was not associated with significant increases in total ERK, total p38,
      or total JNK concentrations. The stress kinases ERK and p38 play an important
      role in caerulein-stimulated exocrine pancreatic overproduction of cytokines. The
      role of JNK needs further evaluation in this experimental model.

PMID- 17175458
TI  - Mechanism of gastric bypass-induced body weight loss: one-year follow-up after
      micro-gastric bypass in rats.
AB  - Bariatric surgery (Roux-en-Y or mini-gastric bypass) is designed to limit food
      intake by creating a small gastric pouch and to reduce nutrient absorption by
      bypassing the long limb of the intestine. We report 1-year follow-up results
      after micro-gastric bypass in rats. Micro-gastric bypass was performed by
      anastomosis of the esophagus and the proximal jejunum. Body weight, body
      composition, bone mineral density, food intake, and serum levels of ghrelin and
      obestatin were measured. Growing rats had a 40% weight reduction 2 months after
      micro-gastric bypass surgery compared to 20% after gastrectomy and 30% after
      stomach bypass (anastomosis of the esophagus and duodenal bulb). Six months after
      micro-gastric bypass surgery, the rats stopped growing compared to controls that
      gained continuously due to expansion of the fat compartment. Adult rats (600 g)
      lost 30% of their body weight 5 months after the micro-gastric bypass, while food
      intake was not reduced. Serum levels of obestatin (but not ghrelin) were reduced
      in rats with micro-gastric bypass. The results suggest that micro-gastric bypass
      efficiently reduced body weight, particularly fat mass; loss of the weight after
      micro-gastric bypass was not due to reduced food intake; and lean tissue and bone
      development were impaired in growing subjects after gastric bypass.

PMID- 17175459
TI  - Bariatric surgery at the extremes of age.
AB  - The safety and efficacy of bariatric surgery in adolescents and especially in
      Medicare population have been challenged. Our aim was to determine short-term (30
      day) and long-term outcomes of bariatric surgery in patients>or=60 years and
      <or=18 years old. Query of our 20-year bariatric surgery database identified 155
      patients>or=60 years and 12 patients<or=18 years. We determined morbidity and
      mortality rates and sent a questionnaire to all surviving patients; 127 of 139
      survivors>or=60 years and all 12 adolescents returned the questionnaire (92%) at
      a mean of 5 years (range 1-19 years). For patients>or=60 years, 30-day mortality
      was 0.7%, serious morbidity delaying discharge was 14%, and 5-year mortality was
      5%. At a mean of 5 years, body mass index (BMI in kg/m2) decreased from a mean
      (+/-SEM) of 46+/-1 to 33+/-1 with a 51% resolution of weight-related
      comorbidities and an 89% subjective overall satisfaction rate. In patients<or=18
      years, all with serious comorbidities, there were no deaths and no serious
      complications. BMI decreased from 55 (range 39-74) to 36 (range 27-53) at 4 years
      (range 1-8 years). Resolution of weight-related comorbidities was 82%, and
      satisfaction with outcome was 83%. Thirty-day hospital mortality (<1%) and 5-year
      mortality (5%) were much lower than reported previously in the senior population,
      with acceptable morbidity and importantly, with satisfactory outcomes. Bariatric
      surgery is safe and effective at high volume centers for patients with morbid
      obesity at both extremes of age.

PMID- 17175460
TI  - Does the position of the alimentary limb in Roux-en-Y gastric bypass surgery make
      a difference?
AB  - Intestinal obstruction and other complications have been reported following Roux
      en-Y gastric bypass (RYGB) surgery. There is controversy of whether the
      alimentary limb should be placed in the retrocolic or antecolic position. A
      retrospective analysis was performed on 444 patients undergoing RYGB surgery for
      morbid obesity during a six year period. During operation, the surgeon chose the
      positioning of the 75-cm alimentary limb based upon technical consideration (the
      presence of adhesions from prior surgical procedures, thickness of the transverse
      mesocolon and mobility of the small bowel mesentery). Group A (216) patients had
      placement of the Roux limb anterior to the transverse colon, and group B (228)
      patients had placement of the limb through an opening created in the transverse
      mesocolon. The average age was 40 years (range 19-64) and the body mass index
      ranged from 40 to 75 kg/m2. Patients were followed for 24-86 months (mean 36
      months). Any patients lost to follow-up were excluded. The average age of
      patients in the study was 40 years (range 19-64 years). Patients in both groups
      were similar in their body mass index and demographic characteristics. Group A
      had 16 patients (7.4%) that had early intolerance to enteral intake, compared to
      13 patients in group B (5.7%, P>0.05). Thirteen patients required reoperation for
      intestinal obstruction (seven patients in group A and six patients in group B
      (P>0.05). Development of anastomotic stricture occurred in one patient (0.5%) in
      group A and three patients (1%, P>0.05) in group B. There were no differences in
      mean operating room times, hospital length of stay, and excess weight lost. No
      other complications during the follow-up period were attributed to the position
      of the alimentary limb. Placement of the Roux limb in the antecolic position is
      may be technically more feasible in some patients and does not appear to be
      associated with more complications. It avoids the risk of an internal hernia
      through the transverse and does not appear to be associated with feeding
      difficulties in the early or late postoperative period.

PMID- 17175461
TI  - Long-term results of conventional myotomy in patients with achalasia: a
      prospective 20-year analysis.
AB  - Myotomy has proved to be an efficient primary therapy in patients with achalasia,
      especially in younger patients (<40 years of age). The results of laparoscopic
      myotomy cannot be finally assessed, on account of the shorter postoperative
      follow-up. Thus, there are considerable data regarding intermediate-term outcomes
      after laparoscopic myotomy. The aim of our study was a 20-year analysis of the
      conventional cardiomyotomy as the underlying basis assessing the results of
      minimal-invasive surgery. Within 20 years (September 1985 through September
      2005), 161 operations for achalasia were performed in our clinic. Enrolled in
      this study were 108 patients with a conventional, transabdominal myotomy in
      combination with an anterior semifundoplication (Dor procedure) and a minimal
      follow-up of 6 months. All patients were prospectively followed and, in addition
      to radiologic and manometric examinations of the esophagus, the patients were
      asked for their clinical symptoms by structured interviews in 2-year intervals.
      The median age at the time of surgery was 44.5 (range, 14-78) years, and 72.2% of
      the patients were males. The median length of the preoperative symptoms was 3
      years (3 months to 50 years), and the postoperative follow-up was 55 (range, 6
      206) months. In 70 (64.8%) patients, a pneumatic dilation had been performed. The
      preoperative Eckardt score of 6 (range, 2-12) could be reduced to 1 (range, 0-4)
      after myotomy (P<0.0001). Consequently, with 97.2% of all patients, a good-to
      excellent result was achieved in the long-term follow-up, corresponding to a
      clinical stage I-II. Postoperatively, 69 patients (63.9%) gained weight. The
      radiologically measured maximum diameter of the esophagus decreased from
      preoperatively 45 (range, 20-75) mm to postoperatively 30 (range, 20-60) mm,
      while the minimum diameter of the cardia increased from 3.4 (range, 1-10) mm to
      10 (range, 5-15) mm. The resting pressure of the lower esophageal sphincter could
      be reduced from 28.4 (range, 9.4-56.0) mm Hg to 8.6 (range, 3.0-22.5) mm Hg.
      Conventional myotomy leads in the long run with high efficiency to an improvement
      of the symptoms evident in achalasia. These results may be regarded as the basis
      for assessment of the minimal-invasive procedure.

PMID- 17175462
TI  - Gender disparities in colorectal cancer screening: true or false?
AB  - To date, nearly all studies examining gender disparities in colorectal cancer
      screening report a lower endoscopic screening rate in women. Using a statewide
      claims database, gender differences in screening rates were analyzed in an
      attempt to validate gender disparities reported in prior survey-based studies.
      Procedural-level dataset containing all patient encounters for 2003 in which a
      colonoscopy or flexible sigmoidoscopy were performed was created. Procedures were
      selected using CPT codes and univariate analysis was performed using SAS v 8.0.
      Statewide for average-risk individuals 50 years or older, 65,232 endoscopic
      procedures were performed in 2003. The majority (83%) of endoscopic screening
      procedures were colonoscopies. Overall, the rate of screening in average-risk
      women 50 years or older (38 procedures/1000 people) was slightly lower than in
      men (42/1000) but not statistically significant. The rates of screening were
      higher in women before the age of 60 years and lower after the age of 60 years.
      No clinically significant difference was found in the type of screening procedure
      performed. Gender disparities in rates and types of colorectal cancer screening
      reported in prior survey studies are not validated in this patient encounter data
      study.

PMID- 17175463
TI  - Hypoxia and reoxygenation: a possible mechanism for placental oxidative stress in
      preeclampsia.
AB  - Preeclampsia is a human pregnancy-specific disorder that is diagnosed by the new
      appearance of hypertension and proteinuria after 20 weeks' gestation. It is a
      leading cause of perinatal morbidity and mortality, and the only intervention
      that effectively reverses the syndrome is delivery. Oxidative stress of the
      placenta is considered to be a key intermediary step in the pathogenesis of
      preeclampsia, but the cause for the stress remains unknown. Hypoxia-reoxygenation
      (H/R) injury, as a result of intermittent placental perfusion secondary to
      deficient trophoblast invasion of the endometrial arteries, is a possible
      mechanism. In this review, we present evidence to show that there is a plausible
      basis from which to assume that blood flow in the intervillous space will be
      intermittent in all normal pregnancies. The intermittency will be exacerbated by
      impaired conversion of the spiral arteries, or by the presence of atherotic
      changes that reduce their caliber as seen in preeclampsia. Placental oxidative
      stress can be the consequences of fluctuations in oxygen concentrations after H/R
      through the actions of reactive oxygen species. On this basis, there will be a
      complete spectrum of placental changes among the normal, the late onset and the
      early onset preeclamptic states. Viewing the syndrome as a continuum of H/R
      insults provides new insight into the pathophysiology of pregnancy that will hope
      fully lead to improved clinical interventions.

PMID- 17175464
TI  - Genotype-phenotype correlation of maternally inherited disorders due to mutations
      in mitochondrial DNA.
AB  - Mitochondrial disorders are heterogeneous systemic ailments that are most often
      caused by maternal inheritance of a variety of mutations of the mitochondrial
      (mt) DNA. Paternal inheritance and somatic mutation are rare. The disorders are
      well recognized not only for the genotypic heterogeneity, but also the phenotypic
      variation among the affected members of a single family. The genotype-phenotype
      correlation of the diversity of the syndromic and non-syndromic features of
      mitochondrial disorders are discussed. Some aspects of the molecular mechanisms
      of this heterogeneity, and the histopathologic findings are highlighted.

PMID- 17175465
TI  - Perioperative vasovagal syncope with focus on obstetric anesthesia.
AB  - Vasovagal syncope refers to a reflex cardiovascular depression that gives rise to
      loss of consciousness with bradycardia and profound vasodilatation. This response
      commonly occurs during regional anesthesia, hemorrhage or supine inferior vena
      cava compression in pregnancy. The changes in circulatory response from the
      normal maintenance of arterial pressure to parasympathetic activation and
      sympathetic inhibition may cause severe hypotension. This change is triggered by
      reduced cardiac venous return as well as episodes of emotional stress, excitement
      or pain. Occasionally, these vasovagal responses may be unpredictable and may
      dramatically proceed to asystole with circulatory collapse, and may even result
      in death. In these circumstances, hypotension may be more severe than that caused
      by bradycardia alone, because of unappreciated vasodilatation. Regional
      anesthesia, decreased venous return, hemorrhage and abnormal fetal presentation
      cumulatively increase the risk of vasovagal syncope in cesarean section patients.
      When a vasovagal response occurs, ephedrine is the drug of first choice because
      of its combined action on the heart and peripheral blood vessels. Epinephrine
      must be used early in established cardiac arrest, especially after high regional
      anesthesia.

PMID- 17175466
TI  - Hip circumference is an important predictor of plasma C-reactive protein levels
      in overweight and obese Taiwanese women.
AB  - OBJECTIVE: To investigate the relationship between serum levels of C-reactive
      protein (CRP) with obesity, insulin resistance and metabolic syndrome in
      overweight or obese Taiwanese women. MATERIALS AND METHODS: Analysis was
      performed on data from 59 overweight or obese women enrolled in a cross-sectional
      study. Pearson's correlation coefficients were determined between CRP and simple
      anthropometric indices, fasting insulin, homeostasis model assessment (HOMA) and
      serum lipid levels. Forward step-wise regression procedure was used to find a
      "best" subset of predictor variables for CRP. RESULTS: CRP was found to have
      significantly positive correlation with body weight, waist circumference, hip
      circumference, body mass index, log of fasting glucose levels, fasting insulin
      levels and HOMA. Forward stepwise regression procedure showed that the best
      predictor for CRP was hip circumference. CONCLUSION: The correlation between CRP
      and insulin resistance or abnormal lipid levels is attributed to their strong
      correlations with obesity.

PMID- 17175467
TI  - Surgical termination of pregnancy: evaluation of 14,903 cases.
AB  - OBJECTIVE: To evaluate the demographic and clinical characteristics of patients
      who underwent surgical termination of pregnancy and to assess the efficacy of the
      termination methods. MATERIALS AND METHODS: This retrospective study was carried
      out on 14,903 healthy women who had intrauterine pregnancy of <or= 10 weeks of
      gestation as determined by transvaginal ultrasonography. All patients underwent
      either suction curettage (SC) with dilatation or SC only. Family planning
      counseling was given to all patients before the procedure and subjects were
      evaluated for any complications after the procedure. RESULTS: SC with dilatation
      was performed in 43.2% of patients and SC only was performed in 56.8%. Mean age
      was 31 +/- 4.3 years. Only 5% of cases were primigravidas and 87% had formal
      education; 91% had one or more surgical abortions for previous pregnancies.
      Before the procedure, 67% were using coitus interruptus, 10% condom, 6%
      intrauterine device, 5% vaginal lavage, and 3% oral contraceptives as the
      contraceptive method, and 9% did not use any contraception. Infection, excessive
      bleeding, retention of fetoplacental material and uterine perforation were
      reported as complications of the procedure. After the procedure and following
      family planning counseling, 92% began to use an efficient, modern contraceptive
      method. CONCLUSION: This study points out that surgical abortion is not a
      contraceptive method. Most surgical abortions can be prevented by effective usage
      of modern contraceptive methods. The importance of well-planned contraceptive
      counseling and education is emphasized. Better family planning counseling and
      education, and the availability of modern contraceptive methods can easily
      decrease the incidence of surgical abortions.

PMID- 17175468
TI  - Pilot study of labor induction with titrated oral misoprostol.
AB  - OBJECTIVE: To evaluate the safety and efficacy of titrated oral misoprostol for
      labor induction at term. MATERIALS AND METHODS: Seventy-seven pregnant women (37
      nullipara and 40 multipara), with medical or obstetric indications for labor
      induction after 37 weeks of gestation and unfavorable cervices (Bishop's score <
      7), were induced according to the principles of titrated oral doses of
      misoprostol against uterine response. Our primary outcome measurements were the
      percentage of patients who had a vaginal delivery within 24 hours of induction
      and the interval from induction to vaginal delivery. Secondary measurements
      included oxytocin requirement, total misoprostol dosage, number of cesarean
      deliveries, induction failure, uterine hyperstimulation rates and neonatal
      outcomes. RESULTS: Seventy-five women (97.4%) experienced active labor within 24
      hours, with 72 (93.5%) completing vaginal delivery within 24 hours. The mean
      interval from induction to vaginal delivery for all the women was 9.7 hours, with
      a 2.3-hour active phase. The mean misoprostol dosage was 206 microg, with eight
      women (10.4%) requiring oxytocin augmentation. There was no uterine
      hyperstimulation or induction failure, except for seven cases of uterine
      tachysystole (9.1%). CONCLUSION: Titrated oral misoprostol is a safe and
      effective method of labor induction because the dosage can be adjusted according
      to individual response.

PMID- 17175469
TI  - Comparison of day 2 tubal embryo transfer with day 3 embryo transfer into the
      uterus of intracytoplasmic sperm injection derived human embryos.
AB  - OBJECTIVE: To compare the results of embryo transfer into the uterus (ET)
      performed on day 3 vs. tubal embryo transfer (TET) on day 2 in couples diagnosed
      with male factor infertility. MATERIALS AND METHODS: We collected data from 34
      and 110 patients who underwent intracytoplasmic sperm injection (ICSI) followed
      by either TET on day 2 or ET on day 3 (January 2001-June 2005), respectively. All
      couples were diagnosed with male factor infertility; there were no tubal or
      uterine factors, diminished ovarian reserve, pelvic adhesions, history of
      polycystic ovary syndrome or previous ovarian surgery. RESULTS: The clinical
      pregnancy rates of day 2 TET and day 3 ET following ICSI were 64.71% and 57.27%
      (p > 0.05), respectively. The corresponding implantation rates were 35.47% and
      29.58% (p > 0.05), respectively. CONCLUSION: The implantation and clinical
      pregnancy rates of ET on the 3rd day following ICSI were similar to the rates
      obtained with TET 2 days after ICSI. Therefore, ET performed 3 days after ICSI
      should be the first choice for couples with male factor infertility, while day 2
      TET remains a good alternative, especially for women with normal tubal function
      and known difficulties of transcervical ET.

PMID- 17175470
TI  - Tuboovarian abscesses in postmenopausal women.
AB  - OBJECTIVE: To compare the clinical features of tuboovarian abscess (TOA) in pre-
      and postmenopausal women. MATERIALS AND METHODS: Between January 1992 and
      December 2000, all patients with surgically documented TOA at National Taiwan
      University Hospital were enrolled into this retrospective study. Salient
      information with respect to the history, current illnesses, risk factors,
      physical findings, laboratory data, surgeries and postoperative complications was
      obtained from medical records. RESULTS: Of 74 patients with TOA, nine were
      postmenopausal women. Compared with the premenopausal group, postmenopausal
      patients were significantly more likely to have contributing medical disorders (p
      < 0.001) and concomitant pelvic malignant tumors (p = 0.037). CONCLUSION:
      Thorough investigation for concomitant pelvic malignant tumors and meticulous
      medical care should be provided for postmenopausal women with TOA.

PMID- 17175471
TI  - Efficacy of treating abdominal wall pain by local injection.
AB  - OBJECTIVE: When a patient's chief complaint is lower abdominal pain, but physical
      and ultrasonic examinations and laboratory tests show no evidence of any
      noticeable disease, physicians may make a wrong diagnosis, such as abdominal
      adhesion, chronic pelvic inflammatory disease, pelvic congestion and even
      psychosomatic disorders. In actuality, the pain may originate from the abdominal
      wall instead of the viscera. Local anesthetics coupled with steroid injections
      not only effectively alleviate the pain but also means that laparoscopy and
      medication can be avoided and is thereby worthy of wide use. Here, we present the
      results for the treatment of abdominal wall pain by local injection. MATERIALS
      AND METHODS: Between January 1994 and December 2005, we treated 211 abdominal
      wall pain patients. Diagnoses were based on the pressure of the abdominal wall
      tender point, which elicited sharp shooting pain during compression, and presence
      of positive Carnett's sign. After confirmation of the trigger point, a fine
      needle was used to inject a mixture of 0.5% bupivacaine 2 mL, 2% lidocaine 3 mL
      and 4 mg betamethasone 1 mL. The patients were examined on a weekly basis and
      underwent reinjection if symptoms recurred. RESULTS: There were 71 patients who
      were lost to or refused treatment or follow-up; the 140 remaining patients were
      evaluated. After trigger point injection in these patients, 95 (67.9%) reported
      no pain at all after treatment. Forty-five (32.1%) patients still had abdominal
      pain and required a second injection. A total of 133 (95%) patients showed
      complete pain resolution. After 3 months of follow-up, 115 (86.5%) patients
      remained free of abdominal pain. CONCLUSION: Local injection for selective
      abdominal wall pain patients produces significant pain relief. The diagnosis of
      abdominal wall pain is an important component in avoiding unnecessary operations
      in patients with abdominal pain.

PMID- 17175472
TI  - Prevalence of urinary frequency in Taiwanese women aged 20-59 years.
AB  - OBJECTIVE: To evaluate the prevalence of daytime urinary frequency among
      Taiwanese women aged 20-59 years. MATERIALS AND METHODS: In 1998, there were an
      estimated 5.9 million female residents aged 20-59 years in Taiwan. A random
      sample of 4,549 women was chosen by multistage sampling. Face-to-face visits with
      3,537 women were completed by trained professional interviewers within 3 months
      of the subjects' selection. Questions about lower urinary tract symptoms,
      sociodemographics, reproduction, and medical and surgical histories were
      recorded. The factors were assessed by frequency and logistic regression analyses
      using a significance level of less than 0.05. RESULTS: The prevalence of urinary
      frequency in Taiwanese women aged 20-59 years was 5.2% (182/3,519); 18
      interviewees did not answer the question about frequency and were excluded. For
      those who complained of frequency, 47.2% voided 8-15 times a day, 37.4% voided 16
      23 times a day, 1.1% voided 24-31 times a day and 14.3% voided more than 31 times
      a day. The prevalence of urinary frequency was not linked to age (p = 0.326).
      CONCLUSION: Urinary frequency is a common symptom in women of all ages and is not
      significantly related to age. More than half of the women interviewed admitted
      that less than an hour occurred between visits to the restroom during the
      daytime.

PMID- 17175473
TI  - Scar endometriosis at the site of cesarean section.
AB  - OBJECTIVE: Scar endometriosis is a rare condition. We report a case of scar
      endometriosis occurring at the site of an old cesarean section scar. CASE REPORT:
      A 29-year-old multiparous woman complained of painful sensation during
      menstruation for 2 years that occurred at the site of her cesarean section
      surgical scar. On examination, there was a firm nodule measuring 2 x 1.5 cm in
      size at the mid-point of the scar. In view of the possibility of scar
      endometriosis, the mass was completely excised. Pathologic findings were
      compatible with scar endometriosis. Postoperatively, danazol was prescribed to
      prevent recurrence. CONCLUSION: A surgical scar becoming painful and swollen
      during menstruation is the classic symptom of scar endometriosis. Causes include
      iatrogenic transplantation of endometrium to the surgical wound. Surgical
      excision is the main treatment. Postoperative GnRH-agonist or danazol may be
      prescribed to patients with scar endometriosis.

PMID- 17175474
TI  - Silent uterine rupture in an unscarred uterus.
AB  - OBJECTIVE: Uterine rupture is one of the most serious obstetric complications,
      with an increased risk of maternal and perinatal morbidity, and even mortality.
      CASE REPORT: A multiparous woman came to our labor room at 41 weeks of gestation
      for induction of labor due to being post-term and having a nonreactive nonstress
      test. She had no history of abdominal or gynecologic surgery. Emergent cesarean
      section was performed due to prolonged decelerations shown on the fetal monitor.
      A 12 cm uterine laceration was identified after opening the abdominal cavity.
      Fortunately, her uterus was preserved and her postoperative condition was stable.
      CONCLUSION: To avoid maternal and fetal morbidity, or even mortality,
      obstetricians should be aware of the possible existence of uterine rupture in an
      unscarred uterus.

PMID- 17175476
TI  - Postcesarean splenic torsion.
AB  - OBJECTIVE: Splenic torsion is an exceedingly rare complication in pregnancy. We
      present a case of acute splenic torsion that manifested after cesarean section
      and which was successfully treated with laparotomy with splenectomy and partial
      pancreatectomy. CASE REPORT: A 35-year-old, gravida 7, para 1, aborta 5, woman
      presented at our hospital for planned cesarean section at 38 weeks of gestation.
      Thrombocytopenia was noted antenatally and enlarged spleen with smooth surface
      and contour was observed at the conclusion of cesarean section. One day after
      delivery, dyspnea and left upper abdominal pain developed. Abdominal computed
      tomography showed a huge abscess in the left anterolateral abdomen and bilateral
      pleural effusion. Acute splenic torsion was highly suspected, but the patient
      refused surgical intervention until the condition exacerbated 21 days after
      delivery. Splenic pedicle strangulation with thrombosis, a severely ischemic
      spleen with rupture and distal pancreatic necrosis were noted during emergent
      laparotomy. She had an uneventful recovery and was discharged 5 days after left
      splenectomy and partial pancreatectomy. CONCLUSION: Splenic torsion is a rare
      cause of acute abdominal pain during pregnancy or postpartum, and the symptoms
      vary depending on the degree of torsion. Early involvement of many complementary
      specialty services enabled early recognition of this rare entity and timely
      definitive treatment.

PMID- 17175475
TI  - Poor prognosis of intraoperative rupture of mature cystic teratoma with malignant
      transformation.
AB  - OBJECTIVE: To present the phenomenon of the postoperative rapid progression of
      mature cystic teratoma (MCT) with malignant transformation (MT) when
      intraoperative spillage occurs during operation. CASE REPORTS: Two patients with
      MCT were treated, one with total hysterectomy plus bilateral salpingo
      oophorectomy in an exploratory laparotomy, and the other with cystectomy with
      laparoscopy, respectively. Tumor spillage occurred during both operations. The
      postoperative pathology showed MCT with MT (squamous cell carcinoma type). Both
      patients were referred to our hospital and underwent treatment (3 months and 8
      days, respectively, after the initial operation). At the secondary laparotomy for
      staging surgery, tumor dissemination was observed in both patients. CONCLUSION:
      Whether or not tumor dissemination is correlated with tumor rupture during
      operation, we emphasize that any patient with a preoperative diagnosis of MCT
      should have it removed intact to avoid the possibly catastrophic event of tumor
      dissemination.

PMID- 17175477
TI  - Fetal ascites and second trimester maternal hepatitis C virus infection.
AB  - OBJECTIVE: To present the first reported case of early second trimester maternal
      hepatitis C virus (HCV) associated with fetal ascites, which was treated with
      fetal paracentesis, and resulted in a successful outcome of a term liveborn
      infant with anti-HCV seropositivity. CASE REPORT: A 26-year-old primigravida
      woman was diagnosed with acute HCV infection at 17 weeks of gestation. Ultrasound
      (US) at 23 weeks showed significant fetal as cites and echogenic bowel, and fetal
      viral infection was suspected. Maternal serum was positive for high HCV-RNA
      titers and cytomegalovirus (CMV) IgG. Amniocentesis, cordocentesis and
      therapeutic fetal paracentesis were performed at 23 weeks. Fetal karyotype was
      46, XX. Cord blood showed anti-HCV positivity and HCV-RNA titer < 10. Amniotic
      fluid was anti-HCV and CMV IgG positive. US at 27 weeks showed complete
      resolution of fetal ascites. A healthy 2,976 g female baby was delivered at 37
      weeks, with anti-HCV seropositivity, high HCV-RNA titers, CMV IgG positive, IgM
      negative and normal liver function tests at the 1-month follow-up. CONCLUSION:
      Second trimester perinatal HCV infection with possible CMV coinfection associated
      with fetal ascites is a rare event. Fetal therapy resulting in a successful
      outcome has not been reported. Prompt fetal therapy with paracentesis in this
      case led to the delivery of a healthy term liveborn baby with anti-HCV
      seropositivity.

PMID- 17175478
TI  - Synchronous ovarian endometrioid adenocarcinoma and endocervical mucinous
      adenocarcinoma.
AB  - OBJECTIVE: We report a rare case of synchronous cancer consisting of ovarian
      endometrioid adenocarcinoma and endocervical mucinous adenocarcinoma. Related
      literature was reviewed and it appeared that no similar case had been reported
      previously. CASE REPORT: A 30-year-old (gravida 1, para 1, abortus 0) woman
      complained of abdominal fullness, chest tightness and dyspnea on exertion of
      several days' duration. Gynecologic sonography showed a right complex adnexal
      cyst, 16 x 14 cm in size. Computed tomography showed an 18 x 16 cm right pelvic
      tumor, with both cystic and solid components, ascites and bilateral massive
      pleural effusion. Cytology of the pleural effusion showed no malignant cells. The
      patient underwent staging surgery. Histology showed moderately to poorly
      differentiated endometrioid adenocarcinoma of the right ovary with extensive
      lymphovascular permeation, as well as paraaortic and bilateral pelvic lymph node
      metastases. Extensive tumor thrombi were observed in the lymphovascular channels
      of the left ovary, bilateral tubes and uterus. Endocervical adenocarcinoma, < 3
      mm in depth, was also identified on the cervix. The final surgical-pathologic
      stage of ovarian endometrioid adenocarcinoma was stage IIIc and of endocervical
      mucinous adenocarcinoma was stage IA1. Adjuvant chemotherapy with carboplatin and
      paclitaxel was prescribed postoperatively, but the malignancy was not controlled
      due to lung, brain and vulva metastases. The patient died of respiratory failure.
      CONCLUSION: The coexistence of primary neoplasms in the ovary and cervix is rare.
      Diagnosis should be based on histologic examination and requires appropriate
      treatment for both tumors.

PMID- 17175479
TI  - Transitional cell carcinoma of the ovary.
AB  - OBJECTIVE: Transitional cell carcinoma (TCC) of the ovary is a rare, recently
      recognized, subtype of ovarian surface epithelial cancer. We present a case of
      TCC of the ovary, managed by staging operation and followed by postoperative
      chemotherapy with carboplatin and cyclophosphamide. CASE REPORT: A 67-year-old
      postmenopausal woman presented with a 2-year history of progressive enlargement
      of an abdominal mass. Pelvic sonography and abdominal computed tomography showed
      a pelvic mass measuring 210 x 165 x 203 mm. The serum CA-125 titer was also
      elevated (65.01 U/mL). A staging operation with total abdominal hysterectomy,
      bilateral salpingo-oophorectomy, infracolic omentectomy and pelvic lymph node
      dissection was performed. After surgery, the pathologic report of the left
      ovarian tumor was TCC, grade 2-3, stage IA. The patient then underwent four
      cycles of postoperative chemotherapy with carboplatin and cyclophosphamide. CA
      125 levels declined to within the normal range after the first cycle of
      chemotherapy. CONCLUSION: TCC of the ovary is a rare subtype of epithelial
      ovarian cancer. It differs from malignant Brenner tumor by the absence of a
      benign or borderline Brenner component. Surgical resection is the primary
      therapeutic approach, and patient outcomes after chemotherapy are better than for
      other types of common epithelial ovarian cancers.

PMID- 17175480
TI  - Spontaneous ovarian hyperstimulation syndrome in a normal singleton pregnancy.
AB  - OBJECTIVE: It is known that most cases of ovarian hyperstimulation syndrome
      (OHSS) are associated with the therapies for ovulation induction. However, OHSS
      may rarely be associated with a spontaneous ovulatory cycle, usually in the case
      of multiple gestations, hypothyroidism or polycystic ovary syndrome. CASE REPORT:
      A case of OHSS in a woman who became pregnant naturally and who had no underlying
      disease is presented here. The patient was managed expectantly with no
      complications. CONCLUSION: Although spontaneous ovarian hyperstimulation is a
      rare entity, it is important to differentiate it from other causes of ovarian
      enlargement. Occasionally, life-threatening situations may occur, but it is
      usually a self-limiting process.

PMID- 17175481
TI  - Paroxysmal nocturnal hemoglobinuria superimposed with preeclampsia.
AB  - OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic
      disorder characterized by complement-mediated intravascular hemolysis. As
      maternal complication of PNH is already severe, it becomes much more complex when
      preeclampsia is superimposed. We present a case of PNH superimposed with severe
      preeclampsia in the third trimester. CASE REPORT: A 30-year-old, gravida 1, para
      0, woman had PNH, diagnosed at the age of 17. Her PNH was stable under
      medication. In 2004, she conceived and had prenatal care at our hospital. At 35
      weeks of gestation, preeclampsia with elevated blood pressure and proteinuria
      were superimposed and managed with close surveillance. A live male baby was
      delivered vaginally at 38 weeks of gestation. During parturition, her blood
      pressure increased to 180/100 mmHg. Thrombocytopenia, hyponatremia, hyperkalemia,
      hypoalbuminemia, elevated liver enzymes and lactate dehydrogenase were also
      noted. Preeclampsia continued to postpartum and eventually disappeared.
      CONCLUSION: The most frequent causes of PNH-related fetomaternal morbidity and
      mortality are hemolysis and thrombosis. The situation becomes even more
      complicated when PNH is superimposed with preeclampsia. Appropriate clinical
      surveillance, awareness of the potential risks of hemolysis and thrombosis, as
      well as evaluation of fetal wellbeing are essential.

PMID- 17175482
TI  - Cardiotocographic and Doppler ultrasonographic findings in a fetus with brain
      death syndrome.
AB  - OBJECTIVE: The diagnosis of brain death syndrome by cardiotocography (CTG) and
      Doppler ultrasonography (US) is reported in a fetus at 35 weeks of gestation.
      CASE REPORT: A 23-year-old, gravida 2, para 0, woman was referred to our hospital
      because of the absence of fetal movements. CTG showed fixed fetal heart rate
      (FHR) pattern. A detailed Doppler US examination of the fetus showed extensive
      cystic lesions of both cerebral hemispheres, polyhydramnios, total absence of
      neuromuscular parameters of biophysical profile (BPP) and the cessation of
      cerebral blood flow. Umbilical cord artery blood gas analysis showed pH 7.3, PaO2
      30 mmHg and PaCO2 35 mmHg. A floppy male infant weighing 2,450 g was delivered
      vaginally at 36 weeks of gestation and the Apgar scores were 1 and 1 at 5 and 10
      minutes, respectively. The neonate died 2 days after delivery. Postmortem
      examination of the brain showed diffuse, anoxic changes with multicystic
      encephalomalacia in both hemispheres and the brain stem. No other maternal or
      placental abnormalities were seen. CONCLUSION: The possibility of intrauterine
      brain death should be considered in all cases of prolonged fixed FHR pattern,
      accompanied by absence of neuromuscular parameters of BPP, polyhydramnios and
      demonstrated cessation of cerebral blood flow by Doppler US. Increased awareness
      of this event may prevent unnecessary emergency cesarean section.

PMID- 17175483
TI  - Prenatal diagnosis and antenatal history of total anomalous pulmonary venous
      return.
AB  - OBJECTIVE: Total anomalous pulmonary venous return (TAPVR) is traditionally
      diagnosed by echocardiography or cardiac catheterization postnatally after the
      appearance of clinical signs. We report a case of TAPVR diagnosed prenatally by
      targeted echocardiography. CASE REPORT: A 17-year-old woman was referred at 34
      weeks of gestation because of persistent bradycardia. Echocardiography showed
      atrial disproportion and no direct pulmonary venous return to the left atrium. A
      female infant was delivered by cesarean section at 38 weeks of gestation.
      Echocardiography and cardiac catheterization were arranged soon after delivery
      and TAPVR was confirmed. The infant underwent surgical repair of TAPVR by
      anastomosis between the left atrium and pulmonary venous confluence as well as
      surgical ligation of the patent ductus arteriosus at the age of 2 days. The
      infant died on the 28th postoperative day due to obstruction of pulmonary venous
      return and respiratory failure. CONCLUSION: With advances in sonographic
      equipment and careful evaluation of cardiac structures, it is possible to
      diagnose TAPVR prenatally. Pulmonary venous anatomy should be checked during
      prenatal examination.

PMID- 17175484
TI  - Hormone therapy and cardiovascular disease.
AB  - As in other Western countries, cardiovascular disease (CVD) is the leading cause
      of death among women in Taiwan, exceeding the mortality from cervical or breast
      cancer. Women generally present with CVD after menopause and later than men,
      since menopause-related estrogen deficiency has been considered to be associated
      with an increased risk for CVD. Thus, coronary artery diseases and stroke are the
      two main contributors of mortality among postmenopausal women. Observational
      studies have reported a reduction in coronary artery disease risk after hormone
      therapy (HT) ranging from 31-44%. However, recent randomized controlled trials
      that evaluated the effect of HT on primary and secondary CVD prevention have
      questioned the efficacy of HT, despite confirming the lipid-lowering effect of
      estrogen. However, a cluster of factors are responsible for the genesis and
      progression of CVD. Until we further evaluate their specific actions and how
      these different factors interact, the issue related to HT and cardiovascular risk
      will remain unsettled. Since these studies have contributed to our understanding
      of the benefits and risks associated with HT, HT use should be individualized
      after consideration of the condition of each postmenopausal patient. Ideally, the
      efficacy of different preparations and dosages of HT in postmenopausal women who
      are at risk of CVD, before atheromatous lesions have developed, should be
      investigated.

PMID- 17175485
TI  - Fetoscopic laser therapy for twin-twin transfusion syndrome.
AB  - Twin-twin transfusion syndrome (TTTS) complicates approximately 1 in 5 of all
      monochorionic, diamniotic twin pregnancies. If of early onset and untreated,
      severe TTTS is associated with a dismal prognosis, with perinatal mortality rates
      exceeding 90%. The most controversial issue regarding the optimal treatment of
      TTTS has centered on the use of amniocentesis or laser until the first and only
      randomized trial on interventions for TTTS was published a couple of years ago,
      comparing laser to amnioreduction. That report confirmed that the laser group had
      a higher likelihood of the survival of at least one twin to 28 days of age and to
      6 months of age. Infants in the laser group also had a lower incidence of cystic
      periventricular leukomalacia and were more likely to be free of neurologic
      complications at 6 months of age (52% vs. 31%, p = 0.003). Although not every
      case of TTTS is an eligible candidate for fetoscopic-guided laser therapy, it is
      recommended that obstetricians who have the chance to manage TTTS in their daily
      practice be familiar with the rationale behind this laser treatment for TTTS.

PMID- 17175486
TI  - Are routine interventions necessary in normal birth?
AB  - Routine interventions during labor and birth, such as perineal shaving and enemas
      before vaginal delivery, continuous intrapartum electronic fetal monitoring
      (EFM), and episiotomy are prevalent in Taiwan, but they may not always be
      necessary. Numerous studies investigating these interventions have failed to find
      absolute benefits for women with uncomplicated and low-risk pregnancies. No
      evidence-based benefits support routine perineal shaving or enemas during labor
      for reducing the risk of perineal wound infection or neonatal infection. The use
      of EFM is associated with an increased rate of operative interventions (vacuum,
      forceps, cesarean delivery) but does not result in a significant decrease in the
      incidence of perinatal death or cerebral palsy. Routine episiotomy does not have
      demonstrable advantages over restrictive episiotomy in the frequency or severity
      of perineal damage or pelvic relaxation.

PMID- 17175487
TI  - Expression of estrogen receptors alfa and beta mRNA and alkaline phosphatase in
      the differentiation of osteoblasts from elderly postmenopausal women: comparison
      with osteoblasts from osteosarcoma cell lines.
AB  - OBJECTIVE: To evaluate the expression of estrogen receptors (ER) alpha and beta,
      and activity of alkaline phosphatase during differentiation of primary osteoblast
      cells (hOB) from aged postmenopausal women and human osteosarcoma cell lines
      (HOS, MG63). MATERIALS AND METHODS: Osteoblast cultures were prepared from the
      upper femur of postmenopausal patients (age, 60-74 years) and HOS. At the
      indicated times (days 5, 10, 15, 20, and 25), alkaline phosphatase activity and
      expression of ERalpha and ERbeta mRNA were evaluated. RESULTS: In both cultures
      of primary hOB and HOS, alkaline phosphatase activity decreased at the osteoblast
      proliferation stage, whereas it subsequently increased at the matrix maturation
      stage. ER beta mRNA was strongly expressed in HOS on day 15 and remained at high
      levels of transcription through to day 25 (matrix maturation phase), whereas
      ERalpha mRNA was barely detectable during osteoblast differentiation. In hOB,
      transcription of ERalpha mRNA was much stronger than that of ERbeta mRNA.
      CONCLUSION: The presence of ERalpha and ERbeta mRNA in osteoblasts supports the
      involvement of estrogen in human bone formation. The developmental expression of
      alkaline phosphatase was not correlated to ER mRNA expression during osteoblast
      differentiation. ER isoforms may have different functions or interact with each
      other during osteoblast differentiation. Since the expression of ER isoforms is
      different between postmenopausal women and osteosarcoma cell lines,
      characteristics of osteosarcoma cell lines may not be suitable as a model for the
      evaluation of estrogen effects on postmenopausal osteoporosis.

PMID- 17175488
TI  - Distinction between paternal and maternal contributions to the tripronucleus in
      human zygotes obtained after in vitro fertilization.
AB  - OBJECTIVE: The aim of this study was to determine the genetic composition of
      tripronuclear (3PN) zygotes. Fluorescence in situ hybridization (FISH) was used
      to quantify the sperm tails in human 3PN zygotes. MATERIALS AND METHODS: Ovarian
      hyperstimulation was performed using a standard long protocol consisting of
      gonadotropin-releasing hormone agonist (GnRHa) with human menopausal
      gonadotropins (HMG) and/or recombinant follicle stimulating hormone (rFSH). Human
      chorionic gonadotropin (hCG) was administered when at least two leading follicles
      reached 18 mm in mean diameter. Oocytes were retrieved from the follicles
      transvaginally under ultrasound guidance 34-36 hours after administration of hCG.
      The oocytes were examined 16-18 hours after fertilization for the presence and
      number of pronuclei. The 3PN zygotes were then fixed and extracted in buffer at
      37 degrees C for 60 minutes. After washing in a blocking solution, the 3PN
      zygotes were prepared for indirect immunofluorescence using monoclonal antibody
      and Hoechst dye 33342 to visualize the number of pronuclei. RESULTS: Twenty-one
      3PN zygotes were randomly collected for evaluation. The number of 3PN zygotes
      containing one, two or four sperm tails were two (10%), 18 (85%) and one (5%),
      respectively. CONCLUSION: Based on our observations, additional pronuclei are
      mainly of paternal origin.

PMID- 17175489
TI  - Preliminary report on the effect of a lower dose of gonadotropin-releasing
      hormone antagonist (cetrorelix) on ovarian hyperstimulation in lower-weight Asian
      women.
AB  - OBJECTIVE: To determine the minimal effective daily dose of gonadotropin
      releasing hormone (GnRH) antagonist in lower-weight Asian women undergoing
      controlled ovarian hyperstimulation (COH). MATERIALS AND METHODS: A prospective
      randomized controlled trial of GnRH antagonist was performed. A total of 58 women
      with body weight of 40-50 kg accepted COH and transvaginal embryo transfer.
      Patients were divided into two groups: Group 1 patients (n = 28) were given a
      fixed cetrorelix dose of 0.2 mg/day; Group 2 patients (n = 30) were given a fixed
      cetrorelix dose of 0.15 mg/day. Cetrorelix was administered from menstrual day 8
      until the day of human chorionic gonadotropin (hCG) administration. Serum
      luteinizing hormone (LH) and estradiol (E2) concentration were measured on the
      day of hCG administration. Gonadotropin dosages, LH and E2 concentrations,
      retrieved oocyte and embryo numbers, ovarian hyperstimulation syndrome (OHSS),
      embryo quality, and the rates of fertilization, implantation and pregnancy in
      both groups were compared. RESULTS: The clinical pregnancy/implantation rates in
      Group 1 were higher than those in Group 2 (28.6%/10.4% vs. 20%/4.1%). The numbers
      of oocytes retrieved/Grade I-II embryos were higher in Group 1 than Group 2
      (10.5/7.8 vs. 8.3/3.9). A lower percentage of LH surge and higher E2 levels on
      the day of hCG administration were observed in Group 1 compared to Group 2
      (5.9%/1,610.8 pg/mL vs. 26.7%/1,023.6 pg/mL). There were no statistical
      differences between the two groups when comparing gonadotropin dosage and OHSS.
      CONCLUSION: The lowest effective dosage of cetrorelix is 0.2 mg in COH and
      pituitary downregulation for lower-weight Asian women.

PMID- 17175490
TI  - Use of mifepristone and sublingual misoprostol for early medical abortion.
AB  - OBJECTIVE: Existing drug-induced abortion techniques involve oral administration
      of 200 mg of mifepristone, followed by oral administration of 600 microg of
      misoprostol 48 hours later, but the effects are variable. As revealed by recent
      research, sublingual and oral administrations of misoprostol are equally
      efficacious in terms of rapid absorption, but the former lasts longer in serum.
      Hence, in the near future, sublingual administration of misoprostol may become
      the most effective way to induce abortion. MATERIALS AND METHODS: Women with
      intrauterine pregnancy up to 49 gestational days received vaginal
      ultrasonography, followed by oral administration of mifepristone 200 mg and
      sublingual administration of misoprostol 600 microg 48 hours later. They returned
      for follow-up consultations 3 and 14 days after. The definition of a successfully
      induced complete medical abortion was that the abortion occurred without surgery
      or evacuating the uterus. RESULTS: A total of 356 women underwent medical
      abortion; the complete abortion rate was 98.3% (350 women). Medical abortion was
      unsuccessful in five (1.7%) women, who eventually had to undergo dilation and
      curettage. Patients found the side effects to be bearable; the reported
      satisfaction rate was 89.9% (325 women). CONCLUSION: Medical abortion for early
      termination of pregnancy should be achieved by oral administration of
      mifepristone, followed by sublingual administration of misoprostol.

PMID- 17175491
TI  - Concurrent use of mifepristone and misoprostol for early medical abortion.
AB  - OBJECTIVE: This study was designed to evaluate the efficacy of using mifepristone
      and misoprostol concurrently for early medical abortion. MATERIALS AND METHODS: A
      total of 90 women with undesired pregnancies <or= 49 days' gestation were
      enrolled. All women concurrently received oral mifepristone 200 mg and vaginal
      misoprostol 800 microg. Follow-up evaluation with transvaginal ultrasonography
      was performed 4 days and 2 weeks after treatment. RESULTS: The complete abortion
      rate was 97.8% (88/90 women). The mean induction to abortion interval was 5.5
      hours. The mean bleeding duration was 11.8 days. Patients found the side effects
      acceptable and reported a 91.1% (82 patients) satisfaction rate. CONCLUSION:
      Concurrent administration of oral mifepristone and vaginal misoprostol is an
      efficacious regimen for medical abortion of pregnancies <or= 49 days of
      gestation.

PMID- 17175492
TI  - Risk factors for urinary frequency in Taiwanese women aged 20-59 years.
AB  - OBJECTIVE: To evaluate the risk factors for daytime urinary frequency in
      Taiwanese women aged 20-59 years. MATERIALS AND METHODS: In 1998, there were
      about 5.9 million female residents aged 29-59 years in Taiwan. A random sample of
      4,549 women within this age group was chosen by multistage sampling. Face-to-face
      interviews with 3,537 women were completed by well-trained professional
      interviewers within 3 months of the subjects being selected. Answers to questions
      about lower urinary tract symptoms, sociodemography and past histories were
      recorded. The factors were assessed by frequency analysis and logistic regression
      analysis using a significance level of less than 0.05. RESULTS: The prevalence of
      daytime urinary frequency was significantly related to diabetes mellitus (p =
      0.038), hypertension (p = 0.016) and previous gynecologic surgery (p = 0.005).
      However, there was no relationship between urinary frequency and body mass index,
      drug allergy, smoking, alcohol consumption, marital status, childbirth, parity,
      hysterectomy, menopause, hormone replacement therapy or age. CONCLUSION: The
      results of this study show relatively high risk of urinary frequency development
      in patients with diabetes mellitus or hypertension. Better quality health
      education of these women, drawing their attention to the possibility of
      gynecologic surgery, is the most important factor in making current gynecologic
      surgery more effective. In addition, more attention given to associated factors
      that are preventable, modifiable or controllable, for example diabetes or
      hypertension, may have an impact on the prevalence of urinary frequency.

PMID- 17175493
TI  - Torsion of a uterine leiomyoma.
AB  - OBJECTIVE: To report a case of torsion of a pedunculated uterine leiomyoma. CASE
      REPORT: A 38-year-old female virgin presented at the emergency department with
      complaints of severe lower abdominal pain on November 30, 2005. A transabdominal
      sonogram revealed multiple uterine masses, including a pedunculated mass. With a
      preoperative diagnosis of torsion of a pedunculated subserosal leiomyoma, the
      patient underwent an abdominal myomectomy. On gross inspection, the resected
      myoma was ischemic, and both focal hemorrhage and necrosis were noted in the
      pathology report. CONCLUSION: Torsion of a pedunculated uterine myoma is rare but
      represents a surgical emergency to improve symptoms and avoid consumptive
      coagulopathy.

PMID- 17175494
TI  - Synchronous occurrence of primary neoplasms in the uterus with squamous cell
      carcinoma of the cervix and adenocarcinoma of the endometrium.
AB  - OBJECTIVE: Synchronous primary malignant neoplasms of the uterus are uncommon.
      Patients with synchronous cervical and endometrial cancers are even rarer. We
      describe a case of cervical squamous cell carcinoma and endometrial endometrioid
      adenocarcinoma occurring simultaneously in a 47-year-old woman presenting with
      massive menstrual bleeding. The concept of synchronous primary malignancies of
      the genital tract is also reviewed in this report. CASE REPORT: A 47-year-old
      overtly obese female presented with menometrorrhagia of over 6 months' duration.
      Pelvic examination detected a large cervix but apparently normal externals.
      Magnetic resonance imaging revealed a mass over the cervical region and
      endometrial lesions in the uterine cavity. Surgical exploration disclosed a
      cervical tumor and erosion of the endometrium. The pathologic findings were
      compatible with synchronous occurrence of primary neoplasms in the uterus with
      squamous cell carcinoma of the cervix and adenocarcinoma of the endometrium.
      CONCLUSION: Synchronous genital tract neoplasms are rare but cause more clinical
      problems than a single neoplasm. It is practical to pay more attention to the
      differential diagnosis of primary and metastatic tumors. The second primary
      cancer that occurs in an individual with endometrial cancer may offer an
      opportunity for early detection. The prognosis for a patient with synchronous
      gynecologic malignancies does not seem to be worse.

PMID- 17175496
TI  - Ectopic molar pregnancy in a cesarean scar.
AB  - OBJECTIVE: To report a case of cesarean scar molar pregnancy. CASE REPORT: A 31
      year-old, gravida 8, para 1, female patient underwent suction curettage for a
      diagnosis of molar pregnancy. However, she had persistent vaginal spotting and
      residual decidual tissue in a cesarean scar. She was successfully treated with
      repeat suction curettage. CONCLUSION: Cesarean scar pregnancy is difficult to
      diagnose and must be considered in the patient with a history of cesarean section
      who has persistent vaginal bleeding after suction curettage. To our knowledge,
      this is the first report of molar pregnancy in a cesarean scar.

PMID- 17175495
TI  - Painless ovarian torsion mimicking a uterine myoma.
AB  - OBJECTIVE: Uterine myoma is the most common benign solid pelvic tumor seen in
      women and is easily demonstrated by pelvic ultrasonography. However, a chronic
      ovarian torsion with entire necrosis may be an exceptional mimicker. We herein
      present an unusual case of painless ovarian torsion similar to a subserous
      uterine myoma. CASE REPORT: A 35-year-old female virgin presented with a palpable
      midline pelvic mass that had been present for 2 months. Ultrasound revealed a
      well-defined, heterogeneous solid mass with echogenic rim that resembled a
      uterine myoma, 10.9 x 9.9 x 7.3 cm in size, just upon the uterus. Surgical
      exploration disclosed an enlarged stony ovary and swollen tube that were both
      twisted. The ovary was clogged up with red meat-like necrotic tissue. The
      pathologic findings were compatible with ovarian torsion, and subsequent
      infarction and necrosis. CONCLUSION: Ovarian torsion is a significant cause of
      acute lower abdominal pain in women and is a gynecologic surgical emergency.
      Nevertheless, surgical strategies are usually impeded because of ambiguous
      warning signs. Clinicians may be misled by certain conditions such as silent
      ovarian torsion. Although there may be no specific indication, the diagnosis of
      ovarian torsion should be considered on finding a pelvic mass.

PMID- 17175497
TI  - Very early stage adenocarcinoma arising from adenomyosis in the uterus.
AB  - OBJECTIVE: Malignant transformations of adenomyosis in premenopausal women with
      normal endometrium are extremely rare. We report a case of adenocarcinoma arising
      from an adenomyotic focus in the uterus, which was found unexpectedly in a woman
      undergoing myomectomy for adenomyosis. CASE REPORT: A 47-year-old premenopausal
      woman presented with massive vaginal bleeding and anemia. She was admitted and
      underwent myomectomy under the initial diagnosis of uterine leiomyoma.
      Microscopic studies revealed endometrioid adenocarcinoma, which was a malignant
      transformation of a focus of adenomyosis in the surgical specimen. A total
      hysterectomy and bilateral salpingo-oophorectomy with pelvic and para-aortic
      lymphadenectomy was then performed. Pathologic studies showed no residual tumors
      in the entire resected specimen except for the previous lesion. The endometrium
      had normal thickness with mild proliferative activity throughout the cavity.
      There was no atrophic or hyperplastic change in the whole endometrium. The
      adenocarcinoma was present exclusively in the myometrium, and a transition
      between the carcinoma and the adenomyotic glands was observed. CONCLUSION: This
      case report presents evidence that adenocarcinoma may a rise de novo from an
      adenomyotic lesion in the uterus.

PMID- 17175498
TI  - Solitary fibrous tumor of the uterus.
AB  - OBJECTIVE: A solitary fibrous tumor is an uncommon soft-tissue tumor and rarely
      occurs in the uterus. We present such a case. CASE REPORT: A 78-year-old woman
      presented with low abdominal pain, and pelvic computed tomography showed a pelvic
      mass attached to the uterus. As malignancy could not be ruled out, exploratory
      laparotomy with complete surgical staging was performed. The results of frozen
      section showed benign mesothelioma-like tumor. Unexpectedly, further
      histopathologic results of the lesion revealed a solitary fibrous tumor, an
      outcome that was subsequently confirmed by means of CD34 immunohistochemical
      stain. CONCLUSION: The behavior of solitary fibrous tumors arising from the
      uterus is difficult to evaluate; therefore, complete surgical excision featuring
      clear margins and comprehensive follow-up is recommended.

PMID- 17175499
TI  - Irradiation-induced uterine malignant mixed mullerian tumor.
AB  - OBJECTIVE: To report a case of a patient with cervical squamous cell carcinoma
      stage IIIB who was diagnosed with malignant mixed mullerian tumor (MMMT) 5 years
      after radiotherapy. CASE REPORT: A 57-year-old female patient with cervical
      squamous cell carcinoma FIGO stage IIIB received pelvic irradiation for her
      disease. After radiotherapy, she was followed-up every 6 months. At 60 months,
      Papanicolaou smear revealed abnormal cancer cells and secondary MMMT was
      diagnosed. The patient underwent surgical treatment followed by chemotherapy.
      However, the cancer recurred 8 months after surgery and the patient died 1 month
      later. CONCLUSION: Patients with cervical cancer administered irradiation many
      years previously remain at high risk of secondary malignancies. In these cases,
      long-term follow-up with extreme caution is mandatory. For patients with any
      types of symptoms, aggressive and immediate investigation is suggested in order
      to detect possible occult malignancies.

PMID- 17175500
TI  - Recurrent breast cancer presents as a single solid ovarian mass and ascites.
AB  - OBJECTIVE: Ovarian malignancy is highly suspected when patients present with an
      ovarian cystic mass lesion accompanied with ascites. However, aside from the
      primary origin, a metastatic lesion should be considered, since the ovary is
      frequently metastasized from cancers of other organs, such as the genital tract,
      gastrointestinal tract, and breast. Herein, we report the case of a patient with
      a left adnexal mass and ascites to emphasize consideration of metastatic ovarian
      tumors from non-gynecologic organs. CASE REPORT: A 47-year-old woman with a
      history of right breast infiltrating lobular carcinoma, T3N0M0, grade 3, was
      treated with modified radical mastectomy and axillary lymph-node dissection in
      July 2001. Tumor recurrence was noted in December 2003. Therefore, she underwent
      palliative radiotherapy and various kinds of chemotherapy. In March 2006, she
      experienced poor appetite and abdominal fullness, and was found to have a 12-cm
      adnexal mass accompanied with ascites. Ovarian cancer was suspected, and
      exploratory laparotomy was performed. However, metastatic carcinoma of the ovary
      of breast origin was finally diagnosed. CONCLUSION: In cases of pelvic tumors in
      patients who have a history of other primary cancers, metastasis should be
      suspected initially. Although the prognoses of these patients seem to be worse,
      intensive cytoreductive surgery would improve quality of life and offer a chance
      of better survival in highly selected patients.

PMID- 17175501
TI  - Angiomyxoma of the umbilical cord.
AB  - OBJECTIVE: Angiomyxoma is a rare tumor of the umbilical cord and is associated
      with increased perinatal morbidity and mortality. However, the management of
      these pregnancies in the third trimester is not clearly defined. We present a
      case of an angiomyxoma of the umbilical cord diagnosed in the second trimester,
      and highlight the contribution of color Doppler imaging to the early diagnosis of
      cord anomalies. CASE REPORT: A 29-year-old, gravida 3, para 1, woman had elevated
      maternal serum alpha-fetoprotein at 17 weeks of gestation. Ultrasonography at 19
      weeks showed a placental mass measuring 2 x 1.5 cm over the insertion site of the
      umbilical cord. The mass slowly enlarged in size, from 2.72 x 1.09 cm at 21 weeks
      to 3.9 x 3.9 cm at 33 weeks. Beyond the cord lesion, the development of the fetus
      was unremarkable. At 38 weeks, a normal female infant was delivered by cesarean
      section due to previous history of cesarean section. A mass measuring 3.2 cm was
      found near the insertion site of the umbilical cord to the placenta. Pathologic
      examination showed proliferation of thin-walled vessels embedded in a myxoid
      stroma, and the endothelial cells were positive for factor VIII-related antigen.
      CONCLUSION: Angiomyxoma is a rare tumor of the umbilical cord and should be
      considered when using prenatal ultrasound for detection of cystic lesion. Color
      Doppler imaging can easily and instantly detect perfusion through the umbilical
      vessels and assess cardiac function. In our case, application of color Doppler
      imaging for monitoring the relationship between the tumor and the adjacent
      vessels allowed the fetus to be delivered at term with a favorable outcome.

PMID- 17175502
TI  - Isolated torsion of the fallopian tube in a 14-year-old adolescent.
AB  - OBJECTIVE: Torsion of adnexa is relatively common, but isolated torsion of the
      fallopian tube is rare. It should be considered in all adolescents who present
      with acute pelvic pain. Laparoscopy or laparotomy is often necessary to establish
      the diagnosis. This report focuses on a 14-year-old girl with isolated tubal
      torsion who presented with acute pelvic pain. CASE REPORT: A 14-year-old
      adolescent was admitted to our hospital because of acute right-sided abdominal
      pain without vomiting and diarrhea. Pelvic ultrasound showed an adnexal mass.
      Conservative treatment was given but did not improve her condition. Emergent
      laparoscopy was performed due to persistent symptoms, which later confirmed the
      diagnosis of isolated torsion of the fallopian tube. Pathology showed hemosalpinx
      with necrosis. CONCLUSION: Isolated torsion of the fallopian tube is an uncommon
      event, especially in adolescents. It must be kept in mind whenever a young girl
      presents with low abdominal pain and pelvic mass on ultrasound. Prompt
      laparoscopic intervention may allow for early diagnosis, treatment and
      preservation of the tube if possible.

PMID- 17175503
TI  - Term pregnancy at the site of atresia following vaginal canalization in a case of
      uterus didelphys with hemivaginal atresia and ipsilateral renal agenesis.
AB  - OBJECTIVE: Uterus didelphys with hemivaginal atresia and ipsilateral renal
      agenesis is a rare syndrome of mullerian anomalies. Term pregnancy at the site of
      atresia is even rarer. CASE REPORT: A 28-year-old married woman presented with
      menometrorrhagia and primary infertility. Pelvic examination led to the suspicion
      of a pelvic mass between the uterus and bladder, and protruding to the right site
      of the paracervix. Ultrasound and magnetic resonance imaging examination revealed
      a left ovarian teratoma, right hematocolpos, and uterus didelphys with atresia of
      the right vagina and ipsilateral renal agenesis. Enucleation of the left ovarian
      teratoma by laparoscopy and drainage of hematocolpos by 2-cm canalization as a
      marsupialization procedure at the right paracervical protruding part under
      sonographic guidance were performed. Thereafter, a term pregnancy in the affected
      side was achieved. The patient underwent cesarean section due to breech
      presentation. CONCLUSION: A greater awareness of the syndrome of uterus
      didelphys, hemivaginal atresia, and ipsilateral renal agenesis should lead to a
      correct diagnosis. We herein report our experience with the correct diagnosis and
      alternative management of this rare syndrome.

PMID- 17175504
TI  - Perinatal maternal undernutrition programs the offspring hypothalamo-pituitary
      adrenal (HPA) axis.
AB  - There is now compelling evidence, coming both from animal and human studies that
      an early exposure to undernutrition is frequently associated with low birth
      weight and programs HPA axis alterations throughout the lifespan. Although animal
      models have reported conflicting findings arising from differences in
      experimental paradigms and species, they have clearly demonstrated that such
      programming not only affects the brain but also the pituitary corticotrophs and
      the adrenal cortex. In fetuses, maternal undernutrition reduces HPA axis function
      and implicates a reduction of placental 11beta-HSD2 activity and a greater
      transplacental transfer of glucocorticoids (GRs). In young adults, usually only
      fine HPA axis alterations were observed, whereas in older ones, maternal
      undernutrition was frequently associated with chronic hyperactivity of this
      neuroendocrine axis. In humans, evidence of HPA axis dysregulation in people who
      were small at birth has recently emerged. Thus, we suggest that such alterations
      in adults may be implicated in the aetiology of several disorders related to the
      metabolic syndrome as well as to immune or inflammatory diseases. To reverse such
      programming, recent experimental reports have shown that postnatal environmental
      interventions, dietary modifications and the use of agents modulating the
      epigenomic state could partly restore physiological functions and thus open new
      therapeutic strategies.

PMID- 17175505
TI  - Examination stress as an ecological inducer of cortisol and psychological
      responses to stress in undergraduate students.
AB  - The purpose of the present study was to investigate basic methodological issues
      related to the usage of an examination stress protocol in studies of
      psychoneuroendocrinology. In the present study, 57 undergraduate students served
      as participants. All subjects provided salivary samples and completed
      psychological inventories during a low examination stress period and again during
      a high examination stress period. Salivary samples were analyzed for cortisol.
      Three major findings were observed. First, the examination stress protocol proved
      to be an effective trigger of elevations in both psychological measures of stress
      and in cortisol levels. Second, sex differences were observed in cortisol levels,
      such that males showed an elevation in cortisol during the high examination
      stress session whereas females did not. Finally, no significant correlations were
      observed between elevations in psychological measures of stress and elevations in
      cortisol levels. These findings suggest that the examination stress protocol used
      in the present study effectively elevated both psychological stress and cortisol
      levels. Furthermore, these findings suggest that there are biological differences
      in how males and females respond to stress. Finally, no evidence was found to
      suggest a relationship between psychological and hormonal levels of stress.
      Together, these findings suggest the need to better define and consider the
      implications of both the specific measures of stress being used and individual
      differences in the subject samples in psychoendocrine studies.

PMID- 17175506
TI  - Modulation by 6-hydroxydopamine of expression of the phenylethanolamine N
      methyltransferase (PNMT) gene in the rat heart during immobilization stress.
AB  - Phenylethanolamine N-methyltransferase (PNMT) is the final enzyme in the
      catecholamine synthesizing cascade that converts noradrenaline (NA) to adrenaline
      (Adr). Both of these catecholamines are physiologically important hormones and
      neurotransmitters in mammals with profound influence on the activity of the
      cardiovascular system. Although PNMT activity and gene expression have been
      reported in the neonatal and also adult rat heart, little is known about the
      identity of the cells expressing PNMT mRNA. In this study, we have shown that
      besides PNMT in neuronal and intrinsic cardiac cells, this enzyme is expressed
      also in rat cardiomyocytes, as shown by immunofluorescence in isolated
      cardiomyocytes. To determine which cells in the heart more sensitively show
      stress-induced changes in PNMT mRNA expression, we performed chemical
      sympathectomy by administration of 6-hydroxydopamine (6-OHDA), which destroys
      catecholaminergic terminals. We determined PNMT mRNA levels in the left atria and
      ventricles of control and stressed rats. In the rats treated with 6-OHDA, PNMT
      mRNA levels were not changed under normal, physiological conditions compared to
      vehicle treated rats. Similar results were observed on isolated cardiomyocytes
      from control and 6-OHDA treated rats. However, 6-OHDA treatment prevented
      immobilization-induced increase in PNMT mRNA expression. The results allow us to
      propose that in the heart, the immobilization-induced increase in PNMT gene
      expression is probably not in cardiomyocytes, but in neuronal cells.

PMID- 17175507
TI  - Corticotrophin-releasing factor type 2 receptor-mediated suppression of
      gonadotrophin-releasing hormone mRNA expression in GT1-7 cells.
AB  - Corticotrophin-releasing factor (CRF) released during stress has been implicated
      in the suppression of the hypothalamo-pituitary-gonadal (HPG) axis, especially
      the gonadotrophin-releasing hormone (GnRH) pulse generator, the central neural
      regulator of pituitary LH and FSH secretion, resulting in reproductive
      dysfunction. The gonadal steroid 17beta-oestradiol (E2) has been shown to enhance
      CRF- and stress-induced suppression of pulsatile LH secretion. In the present
      study, we investigated the potential direct action of CRF on GnRH neurones by
      using GT1-7 cells, an established GnRH cell line. Furthermore, we investigated
      the modulatory influence of E2 on the effects of CRF and expression of CRF type 2
      receptors (CRF-R2). Expression of CRF-R2 in the GT1-7 cells was detected by
      reverse transcription-polymerase chain reaction (RT-PCR). CRF produced a dose
      dependent suppression of GnRH mRNA expression, an effect reversed by the
      selective CRF-R2 antagonist, astressin2-B (Ast2-B). E2 combined with CRF resulted
      in a greater suppression of GnRH expression compared with either treatment alone.
      E2 also increased CRF-R2 expression. These results demonstrate for the first time
      expression of CRF-R2 in the GT1-7 cells and suggest that CRF may directly
      regulate GnRH gene expression, an effect mediated, at least in part, by CRF-R2.
      They also raise the possibility that up-regulation of CRF-R2 may contribute to
      the sensitising influence of E2 on CRF- and stress-induced suppression of the
      GnRH pulse generator.

PMID- 17175508
TI  - Acute restraint stress enhances calcium mobilization and proliferative response
      in splenic lymphocytes from mice.
AB  - Calcium (Ca2+ ) plays an essential role in lymphocyte activation and maturation.
      Acute and chronic stress has been shown to modulate the lymphocyte immune
      response; but the relationship between cytosolic free Ca2+ concentration ([Ca2+
      ]i) and the immune response in lymphocytes following exposure to stress has not
      been examined. In the present study, we investigated the effects of acute
      restraint stress on [Ca2+ ]i and the proliferation of splenic lymphocytes from
      mice. We observed that 2 h of restraint significantly increased plasma
      corticosterone levels in mice. On examining [Ca2+ ]i and the proliferation ex
      vivo of splenic lymphocytes isolated from restraint-stressed mice using fura-2
      and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide,
      respectively, we found that acute restraint stress caused a significant increase
      in resting [Ca2+ ]i and significantly enhanced the ability of concanavalin A (Con
      A; a T-cell-selective mitogen) to increase [Ca2+ ]i but not that of
      lipopolysaccharide (LPS; a B-cell-selective mitogen). In addition, acute
      restraint stress significantly enhanced Con A-stimulated but not LPS-stimulated
      lymphocyte proliferation. Overall, there was a positive correlation between [Ca2+
      ]i and T-cell proliferation following acute restraint stress. The enhancements of
      [Ca2+ ]i and T-cell proliferation were completely suppressed by verapamil (a Ca2+
      channel blocker). These results suggest that acute restraint stress enhances Con
      A-stimulated T-cell proliferation by increasing [Ca2+ ]i via stimulation of Ca2+
      entry.

PMID- 17175509
TI  - 2006 Henry f. Smyth jr. Award lecture historical review--employer responsibility
      for workplace health and safety.
AB  - The Academy of Industrial Hygiene established the Henry F. Smyth Jr. Award in
      1981. The Award is presented to that individual who has recognized the needs of
      the industrial hygiene profession and has made major contributions to fulfill
      those needs, thereby contributing to the improvement of the public welfare. This
      year's Award was presented to John L. Henshaw, CIH, at the 2006 Professional
      Conference on Industrial Hygiene (PCIH) in San Jose, California.

PMID- 17175511
TI  - Asbestos exposure during an abatement project.

PMID- 17175512
TI  - Task- and time-dependent weighting factors in a retrospective exposure assessment
      of chemical laboratory workers.
AB  - A chemical exposure assessment was conducted for a cohort mortality study of 6157
      chemical laboratory workers employed between 1943 and 1998 at four Department of
      Energy sites in Oak Ridge, Tennessee, and Aiken, South Carolina. Previous studies
      of chemical laboratory workers have included members within professional
      societies where exposure assessment was either limited or not feasible, or
      chemical processing employees where laboratory and production workers were
      combined. Because sufficient industrial hygiene records were unavailable for all
      four sites, weighted duration of employment was used as a surrogate for the
      magnitude of exposure. Potential exposure indices were calculated for each worker
      using number of days employed and weighting factors for frequency of contact and
      year of employment. A total of 591 unique laboratory job titles indicative of a
      chemical laboratory worker were collapsed into 18 general job title categories.
      Through discussions with current and retired workers, along with examination of
      historical organizational charts and job descriptions, the percentage of time
      with activities involving the direct handling of chemicals in the laboratory was
      estimated for each job title category. Scaled weighting factors of 1, 0.6, 0.3,
      and 0.05 were assigned to the job title categories representing 100%, 60%, 30%,
      and 5% of daily activities handling chemicals, respectively. Based on limited
      industrial hygiene monitoring data, personal radiation monitoring records, and
      professional judgment, weighting factors that declined 4% annually were applied
      to each year to account for improvements in laboratory technique, advancements in
      instrumentation, improvement in engineering controls, and increased safety
      awareness through time. The study cohort was separated into three categories of
      chemical exposures based on department level information: (1) inorganic, (2)
      mixed inorganic and organic, and (3) unknown. Potential exposure indices ranged
      from 0.15 to 6824.5 with a median value of 377.5 and a mean equal to 884.2. This
      exposure assessment method is useful for epidemiologic analyses when quantitative
      exposure data are absent or insufficient.

PMID- 17175513
TI  - Effect of aviation snip design and task height on upper extremity muscular
      activity and wrist posture.
AB  - Hand tools described as ergonomic in design are intended to reduce exposure to
      physical risk factors associated with work-related musculoskeletal disorders.
      Additionally, using the right tool for the job is believed to reduce exposure
      and, consequently, risk of disease. Sheet metal workers frequently use a cutting
      tool called aviation snips when fabricating and installing ductwork. The purpose
      of this laboratory simulation study was to determine the effect of (1) aviation
      snip design; and (2) work height on muscle activity, wrist posture, and user
      satisfaction among sheet metal workers. We hypothesized that specific aviation
      snips designs would be most appropriate for use at specific heights. Twenty-three
      sheet metal workers used three different designs of aviation snips to make curved
      cuts in sheet metal placed both at waist height and shoulder height. Conventional
      circular snips, straight snips, and an alternate design of offset snips were
      used. Upper extremity muscle activity was measured with surface electromyography,
      wrist posture was measured with electrogoniometry, and user satisfaction was
      rated by the participants on a survey. Statistically significant effects of snip
      design and task height on muscle activity, wrist posture, and user satisfaction
      were observed. However, no snip was preferable for all dependent variables. Work
      height had a greater effect on muscle activity and wrist posture than snip
      design. Field studies are indicated to determine the long-term effect of snip
      design on physical risk factors and risk of musculoskeletal disorders.

PMID- 17175514
TI  - Evaluation of noise attenuation and verbal communication capabilities using three
      ear insert hearing protection systems among airport maintenance personnel.
AB  - The goal of this project was to determine whether one type of earplug would allow
      a user to hear communication in a noisy environment better than two other types
      of earplugs. The three types of earplugs studied are newly available on the
      market. Sonomax SonoCustoms are custom fitted to the user. E-A-R Push-Ins are the
      newest form of foam earplugs, and Howard Leight SmartFits have an adaptable
      shape. One of the earplug manufacturers claimed to have improved verbal
      communications due to the design of the earplug. We hypothesized that the type of
      earplug providing better communication properties would have lower attenuation
      around the communication frequencies compared with the other types. To test this
      hypothesis, we used speech intelligibility and attenuation tests in the
      laboratory on 26 subjects, and real-time video exposure monitoring in the field
      (airport maintenance personnel) for visual communication cues. ANCOVA was used to
      analyze the data from the laboratory study. The type of earplug worn was not
      significant in the model (p-value 0.0849), nor was attenuation of the earplug (p
      value 0.2379). Further analysis showed that attenuation did not differ
      significantly among earplugs (p-value 0.5903). Logistic regression was used to
      analyze the data from the field study. Again, the type of earplug was not
      significant in the model (p-value 0.0965). A comfort questionnaire determined
      that Howard Leight SmartFits and the E-A-R Push-Ins were more comfortable and
      easier to use than the Sonomax HPDs (p-value <0.0001). We found a definite
      difference between manufacturers' attenuation data and our attenuation data,
      especially in the frequencies for 125-1000 Hz. Also, there was no difference in
      frequency and overall attenuation among the HPDs. This resulted in no difference
      in communication abilities among the types of HPDs.

PMID- 17175515
TI  - Performance of a full facepiece, air-purifying respirator against lead aerosols
      in a workplace environment.
AB  - This study evaluated workplace performance of a full facepiece, negative
      pressure, air-purifying respirator with P100 filters in a lead refining plant.
      Air samples for lead were collected inside and outside the respirators worn by
      workers who were properly trained and quantitatively fit tested. Trained
      observers assisted in the study to ensure sample validity. Three to four pairs of
      air samples per day were collected from each worker for a total of 52 valid
      sample sets. Lead was found on all the outside samples, and concentrations were
      below the detection limit for all but one of the inside samples. The single
      measurable inside sample yielded a workplace protection factor (WPF) of 297. WPFs
      for the rest of the samples were estimated using the assumption that lead was
      present at the detection limit for the in-facepiece samples. Calculated WPFs were
      rounded down to the nearest 100 then subjected to a rank and percentile function.
      The 5th percentile WPF was approximately 900 using this approach. These WPFs
      exceed the assigned protection factor (APF) of 50 for this respirator class
      recommended by the National Institute for Occupational Safety and Health and
      listed by the Occupational Safety and Health Administration. These results
      support the APF of 50 for this respirator and indicate the respirator provided
      adequate protection as used in this study.

PMID- 17175520
TI  - Clinical use of laboratory tests for the identification of secondary forms of
      arterial hypertension.
AB  - The prevalence of secondary hypertension can be underestimated if appropriate
      tests are not performed. The importance of selecting patients with a high pre
      test probability of secondary forms of hypertension is first discussed. The
      laboratory tests currently used for seeking a cause of hypertension are
      critically reviewed, with emphasis on their operative features and limitations.
      Strategies to identify primary aldosteronism, the most frequent form of secondary
      hypertension, and to determine its unilateral or bilateral causes are described.
      Treatment entails adrenalectomy in unilateral forms, and mineralocorticoid
      receptor blockade in bilateral forms. Renovascular hypertension is also a common,
      curable form of hypertension, that should be identified as early as possible to
      avoid the onset of cardiovascular target organ damage. The tests for its
      confirmation or exclusion are discussed. The various tests available for the
      diagnosis of pheochromocytoma, which is much rarer than the above but extremely
      important to identify, are also described, with emphasis on recent developments
      in genetic testing. Finally, the tests for diagnosing some rarer monogenic forms
      and other renal and endocrine causes of arterial hypertension are explored.

PMID- 17175521
TI  - Conventional and proteomic technologies for the detection of early stage
      malignancies: markers for ovarian cancer.
AB  - Our understanding of the tumor microenvironment continues to evolve and allows
      for the identification of biomarkers that should detect the presence of early
      stage malignancies. Recent advances in computational analysis and biomedical
      technologies have come together to elucidate signatures associated with cancer
      and that are capable of identifying unique tumor-specific proteins. Within the
      tumor microenvironment, we continue to characterize the proteophysiology of the
      different steps associated with tumor progression. The urgent need for biomarkers
      accurately detecting early-stage epithelial ovarian cancer has prompted us, and
      others, to engage in a search for specific peptide signatures that may
      discriminate transformed cells from those of the normal ovarian microenvironment.
      This endeavor also provides new insights into the biology of the disease, which
      may not only be applicable to detection but may also help to initiate new
      therapies and optimize patient care.

PMID- 17175522
TI  - A high-throughput cell-based assay to identify specific inhibitors of
      transcription factor AP-1.
AB  - The oncogenic transcription factor AP-1 (activator protein-1) is required for
      tumor promotion and progression. Identification of novel and specific AP-1
      inhibitors would be beneficial for cancer prevention and therapy. The authors
      have developed a high-throughput assay to screen synthetic and natural product
      libraries for noncytotoxic inhibitors of mitogen-activated AP-1 activity. The
      cell-based high-throughput screen is conducted in a 384-well format using a
      fluorescent resonance energy transfer (FRET) substrate to quantify the activity
      of a beta-lactamase reporter under the control of an AP-1-dependent promoter. The
      ratiometric FRET readout makes this assay extremely robust and reproducible,
      particularly for use with natural product extracts. To eliminate false positives
      due to cell killing, a cytotoxicity assay was incorporated. The AP-1 beta
      lactamase reporter was validated with inhibitors of kinases located upstream of
      AP-1 and with known natural product inhibitors of AP-1 (nordihydroguaiaretic acid
      and curcumin). The assay was able to identify other known AP-1 inhibitors and
      protein kinase C modulators, as well as a number of chemically diverse compounds
      with unknown mechanisms of action from natural products libraries. Application to
      natural product extracts identified hits from a range of taxonomic groups.
      Screening of synthetic compounds and natural products should identify novel AP-1
      inhibitors that may be useful in the prevention and treatment of cancers.

PMID- 17175523
TI  - Label-free high-throughput functional lytic assays.
AB  - Refractive index-sensitive resonant waveguide grating biosensors are used to
      assay the label-free enzymatic degradation of biomolecules. These assays provide
      a robust means of screening for functional lytic modulators. The biomolecular
      substrates in this study were covalently immobilized through amine groups. Using
      the Corning Epic System, the digestion signatures for multiple protein substrates
      on the biosensors are measured. Label-free digestion profiles for these proteins
      were substrate specific. Similarly, the authors find that the label-free
      digestion is protease specific. Enzyme-substrate pairs were used to evaluate high
      throughput biosensors as tools for screening functional modulators. The lytic
      inhibitor properties for several proteases and dextranase are determined. The
      authors find that the IC50 values for the protease inhibitors agree with the
      reported values for several known inhibitors. The Z' values, using biosensor
      based functional lytic screens, were routinely greater than 0.5, making this
      label-free application feasible for high-throughput screening.

PMID- 17175524
TI  - A novel inhibitor of Mycobacterium tuberculosis pantothenate synthetase.
AB  - Pantothenate synthetase (PS; EC 6.3.2.1), encoded by the panC gene, catalyzes the
      essential adenosine triphosphate (ATP)-dependent condensation of D-pantoate and
      beta-alanine to form pantothenate in bacteria, yeast, and plants; pantothenate is
      a key precursor for the biosynthesis of coenzyme A (CoA) and acyl carrier protein
      (ACP). Because the enzyme is absent in mammals and both CoA and ACP are essential
      cofactors for bacterial growth, PS is an attractive chemotherapeutic target. An
      automated high-throughput screen was developed to identify drugs that inhibit
      Mycobacterium tuberculosis PS. The activity of PS was measured
      spectrophotometrically through an enzymatic cascade involving myokinase, pyruvate
      kinase, and lactate dehydrogenase. The rate of PS ATP utilization was quantitated
      by the reduction of absorbance due to the oxidation of NADH to NAD+ by lactate
      dehydrogenase, which allowed for an internal control to detect interference from
      compounds that absorb at 340 nm. This coupled enzymatic reaction was used to
      screen 4080 compounds in a 96-well format. This discussion describes a novel
      inhibitor of PS that exhibits potential as an antimicrobial agent.

PMID- 17175525
TI  - High-throughput bioluminescence screening of ubiquitin-proteasome pathway
      inhibitors from chemical and natural sources.
AB  - To discover original inhibitors of the ubiquitin-proteasome pathway, the authors
      have developed a cell-based bioluminescent assay and used it to screen
      collections of plant extracts and chemical compounds. They first established a
      DLD-1 human colon cancer cell line that stably expresses a 4Ubiquitin-Luciferase
      (4Ub-Luc) reporter protein, efficiently targeted to the ubiquitin-proteasome
      degradation pathway. The assay was then adapted to 96- and 384-well plate formats
      and calibrated with reference proteasome inhibitors. Assay robustness was
      carefully assessed, particularly cell toxicity, and the statistical Z factor
      value was calculated to 0.83, demonstrating a good performance level of the
      assay. A total of 18,239 molecules and 15,744 plant extracts and fractions
      thereof were screened for their capacity to increase the luciferase activity in
      DLD-1 4Ub-Luc cells, and 21 molecules and 66 extracts inhibiting the ubiquitin
      proteasome pathway were identified. The fractionation of an active methanol
      extract of Physalis angulata L. aerial parts was performed to isolate 2
      secosteroids known as physalin B and C. In a cell-based Western blot assay, the
      ubiquitinated protein accumulation was confirmed after a physalin treatment
      confirming the accuracy of the screening process. The method reported here thus
      provides a robust approach to identify novel ubiquitin-proteasome pathway
      inhibitors in large collections of chemical compounds and natural products.

PMID- 17175526
TI  - Evidence of interaction network evolution by whole-genome duplications: a case
      study in MADS-box proteins.
AB  - Recent investigations on metazoan transcription factors (TFs) indicate that
      single-gene duplication events and the gain and loss of protein domains are 2
      crucial factors in shaping their protein-protein interaction networks. Plant
      genomes, on the other hand, have a history of polyploidy and whole-genome
      duplications (WGDs), and thus, their study helps to understand whether WGDs have
      also had a significant influence on protein network evolution. Here we
      investigate the evolution of the interaction network in the well-studied MADS
      domain MIKC-type proteins, a TF family which plays an important role in both the
      vegetative and the reproductive phases of plant life. We combine phylogenetic
      reconstruction, protein domain analysis, and interaction data from different
      species. We show that, unlike previously analyzed interaction networks, the MIKC
      type protein network displays a characteristic topology, with overall high inter
      subfamily connectivity, shared interactors between paralogs, and conservation of
      interaction patterns across species. The evaluation of the number of MIKC-type
      proteins at key time points throughout the evolution of land plants in the
      lineage leading to Arabidopsis suggested that most duplicates were retained after
      each round of WGD. We provide evidence that an initial network, formed by 9-11
      homodimerizing proteins interacting with each other, existed in the common
      ancestor of all seed plants. This basic structure has been conserved after each
      round of WGD, adding layers of paralogs with similar interaction patterns. We
      thus present the first model where we can show that a network of eukaryotic TFs
      has evolved via rounds of WGD. Furthermore, we found that in subfamilies in which
      the K domain is most diverged, the interactions with other subfamilies have been
      largely lost. We discuss the possibility that such a high proportion of genes
      were retained after each WGD because of their capacity to form higher order
      complexes involving proteins from different subfamilies. The simultaneous
      duplications allowed for the conservation of the quantitative balance between the
      constituents and facilitated sub- and neofunctionalization through differential
      expression of whole units.

PMID- 17175527
TI  - The mitochondrial genome of the moss Physcomitrella patens sheds new light on
      mitochondrial evolution in land plants.
AB  - The phylogenetic positions of bryophytes and charophytes, together with their
      genome features, are important for understanding early land plant evolution. Here
      we report the complete nucleotide sequence (105,340 bp) of the circular-mapping
      mitochondrial DNA of the moss Physcomitrella patens. Available evidence suggests
      that the multipartite structure of the mitochondrial genome in flowering plants
      does not occur in Physcomitrella. It contains genes for 3 rRNAs (rnl, rns, and
      rrn5), 24 tRNAs, and 42 conserved mitochondrial proteins (14 ribosomal proteins,
      4 ccm proteins, 9 nicotinamide adenine dinucleotide dehydrogenase subunits, 5
      ATPase subunits, 2 succinate dehydrogenase subunits, apocytochrome b, 3
      cytochrome oxidase subunits, and 4 other proteins). We estimate that 5 tRNA genes
      are missing that might be encoded by the nuclear genome. The overall
      mitochondrial genome structure is similar in Physcomitrella, Chara vulgaris,
      Chaetosphaeridium globosum, and Marchantia polymorpha, with easily identifiable
      inversions and translocations. Significant synteny with angiosperm and
      chlorophyte mitochondrial genomes was not detected. Phylogenetic analysis of 18
      conserved proteins suggests that the moss-liverwort clade is sister to
      angiosperms, which is consistent with a previous analysis of chloroplast genes
      but is not consistent with some analyses using mitochondrial sequences. In
      Physcomitrella, 27 introns are present within 16 genes. Nine of its intron
      positions are shared with angiosperms and 4 with Marchantia, which in turn shares
      only one intron position with angiosperms. The phylogenetic analysis as well as
      the syntenic structure suggest that the mitochondrial genomes of Physcomitrella
      and Marchantia retain prototype features among land plant mitochondrial genomes.

PMID- 17175528
TI  - Divergent haplotypes and human history as revealed in a worldwide survey of X
      linked DNA sequence variation.
AB  - The population genetic history of a 10.1-kbp noncoding region of the human X
      chromosome was studied using the males of the HGDP-CEPH Human Genome Diversity
      Panel (672 individuals from 52 populations). The geographic distribution of
      patterns of variation was roughly consistent with previous studies, with the
      major exception that 1 highly divergent haplotype (haplotype X, hX) was observed
      at low frequency in widely scattered non-African populations and not at all
      observed in sub-Saharan African populations. Microsatellite (short tandem repeat)
      variation within the sequenced region was low among copies of hX, even though the
      estimated time of ancestry of hX and other sequences was 1.44 Myr. The estimated
      age of the common ancestor of all hX copies was 5,230 years (95% consistency
      index: 2,000-75,480 years). To further address the presence of hX in Africa,
      additional samples from Chad and Tanzania were screened. Five additional copies
      of hX were observed, consistent with a history in which hX was present in Africa
      prior to the migration of modern humans out of Africa and with eastern Africa
      being the source of non-African modern human populations. Taken together, these
      features of hX-that it is much older than other haplotypes and uncommon and
      patchily distributed throughout Africa, Europe, and Asia-present a cautionary
      tale for interpretations of human history.

PMID- 17175529
TI  - VNTRDB: a bacterial variable number tandem repeat locus database.
AB  - Variable number tandem repeat-PCR (VNTR-PCR) is a novel method developed for
      molecular typing of microorganisms. This method has proven useful in
      epidemiological studies in medical microbiology. Although hundreds of bacterial
      genomes have been sequenced, variable number tandem repeats (TRs) derived from
      comparative genome analyses are scarce. This may hamper their application to the
      surveillance of bacteria in molecular epidemiology. Here, we present a freely
      accessible variable number tandem repeat database (VNTRDB) that is intended to be
      a resource for helping in the discovery of putatively polymorphic tandem repeat
      loci and to aid with assay design by providing the flanking sequences that can be
      used in subsequent PCR primer design. In order to reveal possible polymorphism,
      each TR locus was obtained by comparing the sequences between different sets of
      bacterial genera, species or strains. Through this comparison, TRs which are
      unique to a genus can also be identified. Moreover, a visualization tool is
      provided to ensure that the copy number and locus length of repeats are correct.
      The VNTRDB is available at http://vntr.csie.ntu.edu.tw/.

PMID- 17175530
TI  - REDIdb: the RNA editing database.
AB  - The RNA Editing Database (REDIdb) is an interactive, web-based database created
      and designed with the aim to allocate RNA editing events such as substitutions,
      insertions and deletions occurring in a wide range of organisms. The database
      contains both fully and partially sequenced DNA molecules for which editing
      information is available either by experimental inspection (in vitro) or by
      computational detection (in silico). Each record of REDIdb is organized in a
      specific flat-file containing a description of the main characteristics of the
      entry, a feature table with the editing events and related details and a sequence
      zone with both the genomic sequence and the corresponding edited transcript.
      REDIdb is a relational database in which the browsing and identification of
      editing sites has been simplified by means of two facilities to either
      graphically display genomic or cDNA sequences or to show the corresponding
      alignment. In both cases, all editing sites are highlighted in colour and their
      relative positions are detailed by mousing over. New editing positions can be
      directly submitted to REDIdb after a user-specific registration to obtain
      authorized secure access. This first version of REDIdb database stores 9964
      editing events and can be freely queried at
      http://biologia.unical.it/py_script/search.html.

PMID- 17175531
TI  - Interplay of 'induced fit' and preorganization in the ligand induced folding of
      the aptamer domain of the guanine binding riboswitch.
AB  - Riboswitches are highly structured elements in the 5'-untranslated regions (5'
      UTRs) of messenger RNA that control gene expression by specifically binding to
      small metabolite molecules. They consist of an aptamer domain responsible for
      ligand binding and an expression platform. Ligand binding in the aptamer domain
      leads to conformational changes in the expression platform that result in
      transcription termination or abolish ribosome binding. The guanine riboswitch
      binds with high-specificity to guanine and hypoxanthine and is among the smallest
      riboswitches described so far. The X-ray-structure of its aptamer domain in
      complex with guanine/hypoxanthine reveals an intricate RNA-fold consisting of a
      three-helix junction stabilized by long-range base pairing interactions. We
      analyzed the conformational transitions of the aptamer domain induced by binding
      of hypoxanthine using high-resolution NMR-spectroscopy in solution. We found that
      the long-range base pairing interactions are already present in the free RNA and
      preorganize its global fold. The ligand binding core region is lacking hydrogen
      bonding interactions and therefore likely to be unstructured in the absence of
      ligand. Mg2+-ions are not essential for ligand binding and do not change the
      structure of the RNA-ligand complex but stabilize the structure at elevated
      temperatures. We identified a mutant RNA where the long-range base pairing
      interactions are disrupted in the free form of the RNA but form upon ligand
      binding in an Mg2+-dependent fashion. The tertiary interaction motif is stable
      outside the riboswitch context.

PMID- 17175532
TI  - Accurate, high-throughput typing of copy number variation using paralogue ratios
      from dispersed repeats.
AB  - Recent work has demonstrated an unexpected prevalence of copy number variation in
      the human genome, and has highlighted the part this variation may play in
      predisposition to common phenotypes. Some important genes vary in number over a
      high range (e.g. DEFB4, which commonly varies between two and seven copies), and
      have posed formidable technical challenges for accurate copy number typing, so
      that there are no simple, cheap, high-throughput approaches suitable for large
      scale screening. We have developed a simple comparative PCR method based on
      dispersed repeat sequences, using a single pair of precisely designed primers to
      amplify products simultaneously from both test and reference loci, which are
      subsequently distinguished and quantified via internal sequence differences. We
      have validated the method for the measurement of copy number at DEFB4 by
      comparison of results from >800 DNA samples with copy number measurements by
      MAPH/REDVR, MLPA and array-CGH. The new Paralogue Ratio Test (PRT) method can
      require as little as 10 ng genomic DNA, appears to be comparable in accuracy to
      the other methods, and for the first time provides a rapid, simple and
      inexpensive method for copy number analysis, suitable for application to typing
      thousands of samples in large case-control association studies.

PMID- 17175534
TI  - GISMO--gene identification using a support vector machine for ORF classification.
AB  - We present the novel prokaryotic gene finder GISMO, which combines searches for
      protein family domains with composition-based classification based on a support
      vector machine. GISMO is highly accurate; exhibiting high sensitivity and
      specificity in gene identification. We found that it performs well for complete
      prokaryotic chromosomes, irrespective of their GC content, and also for plasmids
      as short as 10 kb, short genes and for genes with atypical sequence composition.
      Using GISMO, we found several thousand new predictions for the published genomes
      that are supported by extrinsic evidence, which strongly suggest that these are
      very likely biologically active genes. The source code for GISMO is freely
      available under the GPL license.

PMID- 17175533
TI  - Genome-wide analyses of retrogenes derived from the human box H/ACA snoRNAs.
AB  - The family of box H/ACA snoRNA is an abundant class of non-protein-coding RNAs,
      which play important roles in the post-transcriptional modification of rRNAs and
      snRNAs. Here we report the characterization in the human genome of 202 sequences
      derived from box H/ACA snoRNAs. Most of them were retrogenes formed using the L1
      integration machinery. About 96% of the box H/ACA RNA-related sequences are found
      in corresponding locations on the chimpanzee and human chromosomes, while the
      mouse shares approximately 50% of these human sequences, suggesting that some of
      the H/ACA RNA-related sequences in primate occurred after the rodent/primate
      divergence. Of the H/ACA RNA-related sequences, 49% are found in intronic regions
      of protein-coding genes and 64 H/ACA-related sequences can be folded to the
      typical secondary structure of the box H/ACA snoRNA family, while 30 of them were
      recognized as functional homologs of their corresponding box H/ACA snoRNAs
      previously reported. Of the 64 sequences with the typical secondary structure of
      the box H/ACA RNA family, 11 were found in EST databases and 5 among which were
      shown to be expressed in more than one human tissue. Notably, U107f is nested in
      an intron of a protein gene coding for nudix-type motif 13, but expressed from
      the opposite strand, and the searching of EST databases revealed it can be
      expressed in liver and spleen, even in melanotic melanoma.

PMID- 17175536
TI  - Nucleus-encoded plastid sigma factor SIG3 transcribes specifically the psbN gene
      in plastids.
AB  - We have investigated the function of one of the six plastid sigma-like
      transcription factors, sigma 3 (SIG3), by analysing two different Arabidopsis T
      DNA insertion lines having disrupted SIG3 genes. Hybridization of wild-type and
      sig3 plant RNA to a plastid specific microarray revealed a strong reduction of
      the plastid psbN mRNA. The microarray result has been confirmed by northern blot
      analysis. The SIG3-specific promoter region has been localized on the DNA by
      primer extension and mRNA capping experiments. Results suggest tight regulation
      of psbN gene expression by a SIG3-PEP holoenzyme. The psbN gene is localized on
      the opposite strand of the psbB operon, between the psbT and psbH genes, and the
      SIG3-dependent psbN transcription produces antisense RNA to the psbT-psbH
      intergenic region. We show that this antisense RNA is not limited to the
      intergenic region, i.e. it does not terminate at the end of the psbN gene but
      extends as antisense transcript to cover the whole psbT coding region. Thus, by
      specific transcription initiation at the psbN gene promoter, SIG3-PEP holoenzyme
      could also influence the expression of the psbB operon by producing psbT
      antisense RNA.

PMID- 17175535
TI  - Two primate-specific small non-protein-coding RNAs in transgenic mice: neuronal
      expression, subcellular localization and binding partners.
AB  - In a rare occasion a single chromosomal locus was targeted twice by independent
      Alu-related retroposon insertions, and in both cases supported neuronal
      expression of the respective inserted genes encoding small non-protein coding
      RNAs (npcRNAs): BC200 RNA in anthropoid primates and G22 RNA in the Lorisoidea
      branch of prosimians. To avoid primate experimentation, we generated transgenic
      mice to study neuronal expression and protein binding partners for BC200 and G22
      npcRNAs. The BC200 gene, with sufficient upstream flanking sequences, is
      expressed in transgenic mouse brain areas comparable to those in human brain, and
      G22 gene, with upstream flanks, has a similar expression pattern. However, when
      all upstream regions of the G22 gene were removed, expression was completely
      abolished, despite the presence of intact internal RNA polymerase III promoter
      elements. Transgenic BC200 RNA is transported into neuronal dendrites as it is in
      human brain. G22 RNA, almost twice as large as BC200 RNA, has a similar
      subcellular localization. Both transgenically expressed npcRNAs formed RNP
      complexes with poly(A) binding protein and the heterodimer SRP9/14, as does BC200
      RNA in human. These observations strongly support the possibility that the
      independently exapted npcRNAs have similar functions, perhaps in translational
      regulation of dendritic protein biosynthesis in neurons of the respective
      primates.

PMID- 17175537
TI  - Association of Dnmt3a and thymine DNA glycosylase links DNA methylation with base
      excision repair.
AB  - While methylcytosines serve as the fifth base encoding epigenetic information,
      they are also a dangerous endogenous mutagen due to their intrinsic instability.
      Methylcytosine undergoes spontaneous deamination, at a rate much higher than
      cytosine, to generate thymine. In mammals, two repair enzymes, thymine DNA
      glycosylase (TDG) and methyl-CpG binding domain 4 (MBD4), have evolved to
      counteract the mutagenic effect of methylcytosines. Both recognize G/T mismatches
      arising from methylcytosine deamination and initiate base-excision repair that
      corrects them to G/C pairs. However, the mechanism by which the methylation
      status of the repaired cytosines is restored has remained unknown. We show here
      that the DNA methyltransferase Dnmt3a interacts with TDG. Both the PWWP domain
      and the catalytic domain of Dnmt3a are able to mediate the interaction with TDG
      at its N-terminus. The interaction affects the enzymatic activity of both
      proteins: Dnmt3a positively regulates the glycosylase activity of TDG, while TDG
      inhibits the methylation activity of Dnmt3a in vitro. These data suggest a
      mechanistic link between DNA repair and remethylation at sites affected by
      methylcytosine deamination.

PMID- 17175539
TI  - Improved nuclear localization of DNA-binding polyamides.
AB  - Regulation of endogenous genes by DNA-binding polyamides requires effective
      nuclear localization. Previous work employing confocal microscopy to study uptake
      of fluorophore-labeled polyamides has demonstrated the difficulty of predicting a
      priori the nuclear uptake of a given polyamide. The data suggest that dye
      identity influences uptake sufficiently such that a dye-conjugate cannot be used
      as a proxy for unlabeled analogs. Polyamides capable of nuclear localization
      unaided by fluorescent dyes are desirable due to size and other limitations of
      fluorophores. Recently, a polyamide-fluorescein conjugate targeted to the hypoxia
      response element (HRE) was found to inhibit vascular endothelial growth factor
      (VEGF) expression in cultured HeLa cells. The current study uses inhibition of
      VEGF expression as a biological read-out for effective nuclear localization of
      HRE-targeted polyamides. We synthesized a focused library of non-fluorescent, HRE
      targeted polyamides in which the C-terminus 'tail' has been systematically
      varied. Members of this library bind the HRE with affinities comparable or
      superior to that of the fluorescein-labeled analog. Although most library members
      demonstrate modest or no biological activity, two non-fluorescent polyamides are
      reported with activity rivaling that of the previously reported fluorescein
      labeled polyamide. We also show evidence that promoter occupancy by HIF-1, the
      transcription factor that binds the HRE, is inhibited by HRE-targeted polyamides.

PMID- 17175538
TI  - Rapid DNA mapping by fluorescent single molecule detection.
AB  - DNA mapping is an important analytical tool in genomic sequencing, medical
      diagnostics and pathogen identification. Here we report an optical DNA mapping
      strategy based on direct imaging of individual DNA molecules and localization of
      multiple sequence motifs on the molecules. Individual genomic DNA molecules were
      labeled with fluorescent dyes at specific sequence motifs by the action of
      nicking endonuclease followed by the incorporation of dye terminators with DNA
      polymerase. The labeled DNA molecules were then stretched into linear form on a
      modified glass surface and imaged using total internal reflection fluorescence
      (TIRF) microscopy. By determining the positions of the fluorescent labels with
      respect to the DNA backbone, the distribution of the sequence motif recognized by
      the nicking endonuclease can be established with good accuracy, in a manner
      similar to reading a barcode. With this approach, we constructed a specific
      sequence motif map of lambda-DNA. We further demonstrated the capability of this
      approach to rapidly type a human adenovirus and several strains of human
      rhinovirus.

PMID- 17175540
TI  - TRDB--the Tandem Repeats Database.
AB  - Tandem repeats in DNA have been under intensive study for many years, first, as a
      consequence of their usefulness as genomic markers and DNA fingerprints and more
      recently as their role in human disease and regulatory processes has become
      apparent. The Tandem Repeats Database (TRDB) is a public repository of
      information on tandem repeats in genomic DNA. It contains a variety of tools for
      repeat analysis, including the Tandem Repeats Finder program, query and filtering
      capabilities, repeat clustering, polymorphism prediction, PCR primer selection,
      data visualization and data download in a variety of formats. In addition, TRDB
      serves as a centralized research workbench. It provides user storage space and
      permits collaborators to privately share their data and analysis. TRDB is
      available at https://tandem.bu.edu/cgi-bin/trdb/trdb.exe.

PMID- 17175541
TI  - Expression of RAB4B, a protein governing endocytic recycling, is co-regulated
      with MHC class II genes.
AB  - The small GTPase RAB4 regulates endocytic recycling, a process that contributes
      to Major Histocompatibility Complex (MHC)-mediated antigen presentation by
      specialized antigen presenting cells (APC) of the immune system. The gene
      encoding the RAB4B isoform of RAB4 was singled out by two complementary genome
      wide screens. One of these consisted of a computer scan to identify genes
      containing characteristic MHC class II-related regulatory sequences. The second
      was the use of chromatin immunoprecipitation coupled to microarrays (ChIP-on
      chip) to identify novel targets of a transcriptional co-activator called the MHC
      class II transactivator (CIITA). We show that the RAB4B gene is regulated by a
      typical MHC class II-like enhancer that is controlled directly by both CIITA and
      the multiprotein transcription factor complex known as the MHC class II
      enhanceosome. RAB4B expression is thus activated by the same regulatory machinery
      that is known to be essential for the expression of MHC class II genes. This
      molecular link between the transcriptional activation of RAB4B and MHC class II
      genes implies that APC boost their antigen presentation capacity by increasing
      RAB4-mediated endocytic recycling.

PMID- 17175542
TI  - Structural basis for sequence-dependent DNA cleavage by nonspecific
      endonucleases.
AB  - Nonspecific endonucleases hydrolyze DNA without sequence specificity but with
      sequence preference, however the structural basis for cleavage preference remains
      elusive. We show here that the nonspecific endonuclease ColE7 cleaves DNA with a
      preference for making nicks after (at 3'O-side) thymine bases but the periplasmic
      nuclease Vvn cleaves DNA more evenly with little sequence preference. The crystal
      structure of the 'preferred complex' of the nuclease domain of ColE7 bound to an
      18 bp DNA with a thymine before the scissile phosphate had a more distorted DNA
      phosphate backbone than the backbones in the non-preferred complexes, so that the
      scissile phosphate was compositionally closer to the endonuclease active site
      resulting in more efficient DNA cleavage. On the other hand, in the crystal
      structure of Vvn in complex with a 16 bp DNA, the DNA phosphate backbone was
      similar and not distorted in comparison with that of a previously reported
      complex of Vvn with a different DNA sequence. Taken together these results
      suggest a general structural basis for the sequence-dependent DNA cleavage
      catalyzed by nonspecific endonucleases, indicating that nonspecific nucleases
      could induce DNA to deform to distinctive levels depending on the local sequence
      leading to different cleavage rates along the DNA chain.

PMID- 17175543
TI  - Cognitive function in childhood and early adulthood and injuries later in life:
      the Metropolit 1953 male birth cohort.
AB  - BACKGROUND: It has been suggested that cognitive function in childhood is a
      modifiable risk factor for adult injury. This study examines the relationship
      between cognitive function measured at the age of 12 and 18 years and fatal and
      non-fatal injuries later in adult life. METHODS: A total of 11 532 males born in
      Copenhagen, Denmark in 1953 were followed from 1978 until 2001 with outcomes
      (death from and hospital admission for unintentional injury) obtained from
      national registers. At the age of 12 years, 7987 of these cohort members had
      completed a questionnaire, which included information on cognitive performance.
      In addition, cognitive test scores measured on most (90%) cohort members were
      retrieved from the conscription board records (18 years). RESULTS: During follow
      up, 100 of the men died as a result of and 2123 had been admitted to hospital at
      least once for injury. Cognitive function measured at both the age of 12 and 18
      years was inversely associated with any form of unintentional injury. Adjustment
      for educational attainment at the age of 18 years attenuated these associations
      but did not remove them completely. The association was most evident for falls
      and poisoning, while associations with other injury types were weaker and
      disappeared after adjustment for educational status. Cognitive function was
      associated with repeated hospital admissions for injuries as well as length of
      hospital stay. CONCLUSIONS: We found marked inverse associations between
      cognitive function measured in ages 12 and 18 years and adult risk of fatal or
      non-fatal unintentional injury. An overall increase in educational level may
      result in a reduction in adult injury risk.

PMID- 17175544
TI  - Short-run economic effects of the Scottish smoking ban.
AB  - BACKGROUND: We estimated the short-run economic impacts of the Scottish smoking
      ban on public houses. Previous findings on the effect of smoking bans on the
      hospitality sector have mainly focused on the United States. These studies have
      mostly found no negative economic effects of such legislation on the hospitality
      sector in the long run. However, differences in the social use of public houses
      in Great Britain in comparison with the United States may lead to different
      findings. METHODS: We used a quasi-experimental research design that compared the
      sales and number of customers in public houses located in Scotland before and
      after the Scottish smoking ban was introduced, relative to a control group of
      establishments across the English border where no ban was imposed. To perform
      this analysis, we collected data on 2724 pubs, 1590 in Scotland and 1134 in
      Northern England by phone interviews using quota sampling. RESULTS: We found that
      the Scottish ban led to a 10% decrease in sales [P = 0.02, 95% confidence
      interval (CI) -19% to -2%] and a 14% decrease in customers (P = 0.02, 95% CI -26%
      to -2%). CONCLUSION: Our study suggests that the Scottish smoking ban had a
      negative economic impact on public houses, at least in the short run, due in part
      to a drop in the number of customers.

PMID- 17175545
TI  - Using case vignettes to measure HIV-related stigma among health professionals in
      China.
AB  - BACKGROUND: We examined Chinese health professionals' attitudes towards patients
      with AIDS vs patients with hepatitis B. METHODS: A representative sample of 1101
      Chinese health professionals was used. Prejudicial attitudes and willingness to
      interact were measured based on two case vignettes. RESULTS: Statistical analyses
      revealed that health professionals had negative biases against acquired
      immunodeficiency syndrome (AIDS) patients and reported much less willingness to
      interact with AIDS patients than hepatitis B patients. Perceived risk of
      infection at work was also negatively associated with willingness to interact
      with patients with human immunodeficiency virus (HIV)/AIDS, but relationships
      varied by profession. CONCLUSIONS: This study underscores the importance of
      developing and implementing stigma reduction interventions in health care
      settings to address attitudinal biases and discrimination in clinical practice.

PMID- 17175546
TI  - The relationship between parity and overweight varies with household wealth and
      national development.
AB  - BACKGROUND: Recent studies support a positive relationship between parity and
      overweight among women of developing countries; however, it is unclear whether
      these effects vary by household wealth and national development. Our objective
      was to determine whether the association between parity and overweight [body mass
      index (BMI) > or =25 kg/m(2)] in women living in developing countries varies with
      levels of national human development and/or household wealth. METHODS: We used
      data from 28 nationally representative, cross-sectional surveys conducted between
      1996 and 2003 (n = 275 704 women, 15-49 years). The relationship between parity
      and overweight was modelled using logistic regression, controlling for several
      biological and sociodemographic factors and national development, as reflected by
      the United Nations' Human Development Index. We also modelled the interaction
      between parity and national development, and the three-way interaction between
      parity, household wealth and national development. RESULTS: Parity had a weak,
      positive association with overweight, which varied by household wealth and
      national development. Among the poorest women and women in the second tertile of
      household wealth, parity was positively related to overweight only in the most
      developed countries. Among the wealthiest women, parity was positively related to
      overweight regardless of the level of national development. CONCLUSIONS: As
      development increases, the burden of parity-related overweight shifts to include
      poor as well as wealthy women. In the least-developed countries, programmes to
      prevent parity-related overweight should target wealthy women, whereas such
      programmes should be provided to all women in more developed countries.

PMID- 17175547
TI  - Prospective study of hormonal contraception and women's risk of HIV infection in
      South Africa.
AB  - BACKGROUND: Many women using hormonal contraceptives are also at risk of sexually
      transmitted HIV infection, but data are mixed on whether hormonal contraception
      increases women's risk of HIV. We investigated associations between HIV incidence
      and use of combined oral contraceptives (COC), norethindrone enanthate (NET-EN)
      or depot medroxyprogesterone acetate (DMPA) in a cohort of South African women.
      METHODS: Participants were 4200 HIV-negative women aged 35-49 years enrolled into
      a cervical cancer screening trial. At enrollment, women were tested for sexually
      transmitted infections and reported on their sexual behaviour and contraceptive
      use. During the 24 months of follow-up, women reported on their sexual behaviours
      and contraceptive use and underwent repeat HIV testing. RESULTS: During the 5010
      person-years of follow-up, 111 incident HIV infections were observed (HIV
      incidence, 2.2 infections/100 person-years). At enrollment, 21% of women reported
      using hormonal contraception, primarily DMPA (14% of all women) or NET-EN (5%).
      After adjusting for sexual risk behaviours and sexually transmitted infections,
      the incidence of HIV was similar among women using COC, NET-EN or DMPA compared
      with women not using any hormonal method [incidence rate ratios and 95%
      confidence intervals, 0.65, 0.16-2.66; 0.79, 0.31-2.02 and 0.96, 0.58-1.59,
      respectively]. There was also no association between increased duration of DMPA
      use and HIV incidence (P-value for trend, 0.51). CONCLUSIONS: These findings
      contribute to the evidence from general population cohorts of women that hormonal
      contraceptive use is not associated with increased risk of HIV acquisition.
      Nonetheless, family planning services are an important venue for HIV prevention
      activities.

PMID- 17175548
TI  - Women in novel occupational roles: mental health trends in the UK Armed Forces.
AB  - BACKGROUND: There is uncertainty about whether women in the military have more
      psychological symptoms than men and whether psychological symptoms have increased
      over time. The aims of this study were to assess changes in psychological
      symptoms in military women over time, to compare them with men, and assess the
      effect of deployment. METHODS: Two cross-sectional studies based on random
      samples of the Armed Forces were used to assess the effects of deployment to the
      Gulf and Iraq Wars. We selected for the analyses all the women and a 20% random
      sample of men who completed a questionnaire stratified by rank. We assessed
      psychological distress, number of symptoms, post-traumatic stress reaction
      (PTSR), chronic fatigue and alcohol misuse. RESULTS: There has been an increase
      in psychological symptoms, including alcohol misuse, in those not deployed to the
      Gulf or Iraq Wars, especially in women. The odds ratios for PTSR [5.82 (95% CI:
      1.27-26.71)], multiple symptoms [8.49 (1.97-36.65)] and alcohol misuse [6.20
      (2.09-18.37)] were higher in women than in men in the non-deployed samples.
      Psychological distress and chronic fatigue was more common in women, and alcohol
      misuse, was more common in men. In women, psychological symptoms were positively
      associated with deployment in the Gulf War, but not the Iraq War. CONCLUSION:
      Psychological symptoms in the Armed Forces have increased over time regardless of
      gender, in those not deployed. The association between gender and psychological
      symptoms has not changed over time. The deployment effect in women is similar to
      that described in men.

PMID- 17175549
TI  - Nitrate supply affects ammonium transport in canola roots.
AB  - Plants may suffer from ammonium (NH4+) toxicity when NH4+ is the sole nitrogen
      source. Nitrate (NO3-) is known to alleviate NH4+ toxicity, but the mechanisms
      are unknown. This study has evaluated possible mechanisms of NO3- alleviation of
      NH4+ toxicity in canola (Brassica napus L.). Dynamics of net fluxes of NH4+, H+,
      K+ and Ca2+ were assessed, using a non-invasive microelectrode (MIFE) technique,
      in plants having different NO3- supplies, after single or several subsequent
      increases in external NH4Cl concentration. After an increase in external NH4Cl
      without NO3-, NH4+ net fluxes demonstrated three distinct stages: release (tau1),
      return to uptake (tau2), and a decrease in uptake rate (tau3). The presence of
      NO3- in the bathing medium prevented the tau1 release and also resulted in slower
      activation of the tau3 stage. Net fluxes of Ca2+ were in the opposite direction
      to NH4+ net fluxes, regardless of NO3- supply. In contrast, H+ and K+ net fluxes
      and change in external pH were not correlated with NH4+ net fluxes. It is
      concluded that (i) NO3- primarily affects the NH4+ low-affinity influx system;
      and (ii) NH4+ transport is inversely linked to Ca2+ net flux.

PMID- 17175550
TI  - Sorghum stay-green QTL individually reduce post-flowering drought-induced leaf
      senescence.
AB  - Sorghum is an important source of food, feed, and biofuel, especially in the semi
      arid tropics because this cereal is well adapted to harsh, drought-prone
      environments. Post-flowering drought adaptation in sorghum is associated with the
      stay-green phenotype. Alleles that contribute to this complex trait have been
      mapped to four major QTL, Stg1-Stg4, using a population derived from BTx642 and
      RTx7000. Near-isogenic RTx7000 lines containing BTx642 DNA spanning one or more
      of the four stay-green QTL were constructed. The size and location of BTx642 DNA
      regions in each RTx7000 NIL were analysed using 62 DNA markers spanning the four
      stay-green QTL. RTx7000 NILs were identified that contained BTx642 DNA completely
      or partially spanning Stg1, Stg2, Stg3, or Stg4. NILs were also identified that
      contained sub-portions of each QTL and various combinations of the four major
      stay-green QTL. Physiological analysis of four RTx7000 NILs containing only Stg1,
      Stg2, Stg3, or Stg4 showed that BTx642 alleles in each of these loci could
      contribute to the stay-green phenotype. RTx7000 NILs containing BTx642 DNA
      corresponding to Stg2 retained more green leaf area at maturity under terminal
      drought conditions than RTx7000 or the other RTx7000 NILs. Under post-anthesis
      water deficit, a trend for delayed onset of leaf senescence compared with RTx7000
      was also exhibited by the Stg2, Stg3, and Stg4 NILs, while significantly lower
      rates of leaf senescence in relation to RTx7000 were displayed by all of the Stg
      NILs to varying degrees, but particularly by the Stg2 NIL. Greener leaves at
      anthesis relative to RTx7000, indicated by higher SPAD values, were exhibited by
      the Stg1 and Stg4 NILs. The RTx7000 NILs created in this study provide the
      starting point for in-depth analysis of stay-green physiology, interaction among
      stay-green QTL and map-based cloning of the genes that underlie this trait.

PMID- 17175551
TI  - Identification of transcripts potentially involved in barley seed germination and
      dormancy using cDNA-AFLP.
AB  - Freshly harvested barley seeds are considered as dormant since they do not
      germinate at temperatures above 20 degrees C. This dormancy is broken during dry
      storage. Molecular regulation of dormancy was investigated using cDNA-AFLP to
      identify transcripts differentially expressed in dormant and non-dormant embryos.
      Transcript patterns in embryos from dry dormant and non-dormant seeds and from
      both seeds imbibed for 5 h at 30 degrees C, a temperature at which dormancy is
      expressed, were compared. Thirty-nine Transcript-Derived Fragments (TDF) that
      were reproducibly differentially expressed among treatments were identified, and
      25 of these were cloned and sequenced. Among these, eight transcripts were
      observed to be differentially expressed during after-ripening, seven of which
      decline, probably due to post-maturation degradation. HV13B, TDF identified as
      having homology to fructose-6-phosphate-2-kinase/fructose-2,6-biphosphatase, may
      have a role in the maintenance of dormancy in barley and probably in other
      cereals. During the first 5 h of imbibition, there was expression of 24 TDF which
      was apparently independent of dormancy, revealing putative epigenetic regulation.
      This was typified by HV44A, a SET domain protein. Seven TDF differentially
      expressed, and especially HV12D, HV42B, and HV32B, in dormant and non-dormant
      seeds were potential signalling elements. HV12D had homology with an ARIADNE gene
      which could be implicated in ABA signalling.

PMID- 17175552
TI  - Altered cytokinin metabolism affects cytokinin, auxin, and abscisic acid contents
      in leaves and chloroplasts, and chloroplast ultrastructure in transgenic tobacco.
AB  - Cytokinins (CKs) are involved in the regulation of plant development including
      plastid differentiation and function. Partial location of CK biosynthetic
      pathways in plastids suggests the importance of CKs for chloroplast development.
      The impact of genetically modified CK metabolism on endogenous CK, indole-3
      acetic acid, and abscisic acid contents in leaves and isolated intact
      chloroplasts of Nicotiana tabacum was determined by liquid chromatography/mass
      spectrometry and two-dimensional high-performance liquid chromatography, and
      alterations in chloroplast ultrastructure by electron microscopy. Ectopic
      expression of Sho, a gene encoding a Petunia hybrida isopentenyltransferase, was
      employed to raise CK levels. The increase in CK levels was lower in chloroplasts
      than in leaves. CK levels were reduced in leaves of tobacco harbouring a CK
      oxidase/dehydrogenase gene, AtCKX3. The total CK content also decreased in
      chloroplasts, but CK phosphate levels were higher than in the wild type. In a
      transformant overexpressing a maize beta-glucosidase gene, Zm-p60.1, naturally
      targeted to plastids, a decrease of CK-O-glucosides in chloroplasts was found. In
      leaves, the changes were not significant. CK-O-glucosides accumulated to very
      high levels in leaves, but not in chloroplasts, of plants overexpressing a ZOG1
      gene, encoding trans-zeatin-O-glucosyltransferase from Phaseolus lunatus.
      Manipulation of the CK content affected levels of indole-3-acetic and abscisic
      acid. Chloroplasts of plants constitutively overexpressing Sho displayed
      ultrastructural alterations including the occasional occurrence of crystalloids
      and an increased number of plastoglobuli. The other transformants did not exhibit
      any major differences in chloroplast ultrastructure. The results suggest that
      plant hormone compartmentation plays an important role in hormone homeostasis and
      that chloroplasts are rather independent organelles with respect to regulation of
      CK metabolism.

PMID- 17175553
TI  - The role of abscisic acid in disturbed stomatal response characteristics of
      Tradescantia virginiana during growth at high relative air humidity.
AB  - In this study, the role of abscisic acid (ABA) in altered stomatal responses of
      Tradescantia virginiana leaves grown at high relative air humidity (RH) was
      investigated. A lower ABA concentration was found in leaves grown at high RH
      compared with leaves grown at moderate RH. As a result of a daily application of
      20 microM ABA to leaves for 3 weeks during growth at high RH, the stomata of ABA
      treated leaves grown at high RH showed the same behaviour as did the stomata of
      leaves grown at moderate RH. For example, they closed rapidly when exposed to
      desiccation. Providing a high RH around a single leaf of a plant during growth at
      moderate RH changed the stomatal responses of this leaf. The stomata in this leaf
      grown at high RH did not close completely in response to desiccation in contrast
      to the stomata of the other leaves from the same plant. The ABA concentration on
      a fresh weight basis, though not on a dry weight basis, of this leaf was
      significantly lower than that of the others. Moreover, less closure of stomata
      was found in the older leaves of plants grown at high RH in response to
      desiccation compared with younger leaves. This was correlated with a lower ABA
      concentration in these leaves on a fresh weight basis, though not on a dry weight
      basis. Stomata of leaves grown at moderate RH closed in response to short-term
      application of ABA or sodium nitroprusside (SNP), while for leaves grown at high
      RH there was a clear difference in stomatal responses between the leaf margins
      and main-vein areas. The stomatal aperture in response to short-term application
      of ABA or SNP at the leaf margins of leaves grown at high RH remained
      significantly wider than in the main-vein areas. It was concluded that: (i) a
      long-term low ABA concentration in well-watered plants during growth at high RH
      could be a reason for less or no stomatal closure under conditions of drought
      stress; and (ii) the long-term ABA concentration on a fresh weight basis rather
      than on a dry weight basis is likely to be responsible for structural or
      physiological changes in stomata during leaf growth.

PMID- 17175554
TI  - Intact plant MRI for the study of cell water relations, membrane permeability,
      cell-to-cell and long distance water transport.
AB  - Water content and hydraulic conductivity, including transport within cells, over
      membranes, cell-to-cell, and long-distance xylem and phloem transport, are
      strongly affected by plant water stress. By being able to measure these transport
      processes non-invasely in the intact plant situation in relation to the plant
      (cell) water balance, it will be possible explicitly or implicitly to examine
      many aspects of plant function, plant performance, and stress responses. Nuclear
      magnetic resonance imaging (MRI) techniques are now available that allow studying
      plant hydraulics on different length scales within intact plants. The information
      within MRI images can be manipulated in such a way that cell compartment size,
      water membrane permeability, water cell-to-cell transport, and xylem and phloem
      flow hydraulics are obtained in addition to anatomical information. These
      techniques are non-destructive and non-invasive and can be used to study the
      dynamics of plant water relations and water transport, for example, as a function
      of environmental (stress) conditions. An overview of NMR and MRI methods to
      measure such information is presented and hardware solutions for minimal invasive
      intact plant MRI are discussed.

PMID- 17175555
TI  - Disruption of iron homeostasis increases phosphine toxicity in Caenorhabditis
      elegans.
AB  - The aim of this study is to identify the biochemical mechanism of phosphine
      toxicity and resistance, using Caenorhabditis elegans as a model organism. To
      date, the precise mode of phosphine action is unclear. In this report, we
      demonstrate the following dose-dependent actions of phosphine, in vitro: (1)
      reduction of ferric iron (Fe3+) to ferrous iron (Fe2+), (2) release of iron from
      horse ferritin, (3) and the peroxidation of lipid as a result of iron release
      from ferritin. Using in situ hybridization, we show that the ferritin genes of C.
      elegans, both ferritin-1 and ferritin-2, are expressed along the digestive tract
      with greatest expression at the proximal and distal ends. Basal expression of the
      ferritin-2 gene, as determined by quantitative PCR, is approximately 80 times
      that of ferritin-1. However, transcript levels of ferritin-1 are induced at least
      20-fold in response to phosphine, whereas there is no change in the level of
      ferritin-2. This resembles the reported pattern of ferritin gene regulation by
      iron, suggesting that phosphine toxicity may be related to an increase in the
      level of free iron. Indeed, iron overload increases phosphine toxicity in C.
      elegans at least threefold. Moreover, we demonstrate that suppression of ferritin
      2 gene expression by RNAi, significantly increases sensitivity to phosphine. This
      study identifies similarities between phosphine toxicity and iron overload and
      demonstrates that phosphine can trigger iron release from storage proteins,
      increasing lipid peroxidation, leading to cell injury and/or cell death.

PMID- 17175556
TI  - In vitro and in vivo evaluation of the estrogenic, androgenic, and progestagenic
      potential of two cyclic siloxanes.
AB  - The purpose of these experiments was to determine the potential estrogenic,
      androgenic, and progestagenic activity of two cyclic siloxanes,
      octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5). Receptor
      binding experiments and a luciferase reporter gene assay were used to determine
      if the materials were able to bind and activate either the estrogen receptors
      (ERs) or progesterone receptors (PRs)-alpha or beta. The rat uterotrophic assay
      (RUA) for estrogenic activity and the Hershberger assay for androgenic activity
      were utilized as the in vivo assays. For the ER-binding studies, D4 was shown to
      bind to ERalpha but not to ERbeta. D5 did not bind to either of the two
      receptors. D4 activated the reporter gene at 10 microM, while D5 was considered
      negative in the estrogen reporter gene assay. Neither material was a ligand for
      the PRs. Both the RUA and Hershberger assays were conducted using whole-body
      inhalation of the two materials for 16 h/day. D4 resulted in a small but
      significant increase in both wet and blotted uterine weight as well as increases
      in both luminal and glandular epithelial cell height in both Sprague Dawley and
      Fischer 344 rats. D5 was negative in both rat strains, indicating that D5 does
      not possess estrogenic activity. Neither material possessed any significant
      antiestrogenic activity. Both materials were negative in the Hershberger assay
      indicating that neither material possesses any significant androgenic activity.
      Our studies have shown that D4 exhibits a low affinity for ERalpha in vitro and a
      weakly estrogenic response in vivo.

PMID- 17175557
TI  - Determination of phospholipidosis potential based on gene expression analysis in
      HepG2 cells.
AB  - Phospholipidosis (PLD) is characterized by an intracellular accumulation of
      phospholipids in lysosomes and the concurrent development of concentric lamellar
      bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified
      17 genes as potential biomarkers of PLD in HepG2 cells. The present study was
      undertaken to determine if this set of genes measured by quantitative PCR could
      be validated in the same cell line. The objective was also to investigate the
      dose-response relationship to further validate the assay and to select the
      concentrations to use for screening activities. In a first experiment (one
      concentration tested), out of the 17 genes, the best gene biomarkers of PLD
      (i.e., 11 genes) were selected for practical screening reasons. Based on these
      genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were
      identified as positive and all the negative compounds (i.e., five of five) were
      also confirmed. When the data obtained in the first experiment were compared to
      the data by Sawada et al., (2005) the coefficient of correlation calculated was
      slightly higher than 75%. In the second experiment (26 compounds [all 17
      compounds from the first experiment plus 9 other compounds] tested at a minimum
      of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were
      identified as such and all the negative controls (six compounds) were also
      confirmed. Three compounds likely to induce PLD were identified as positive in
      our assay. Finally, two compounds for which no data are available were also
      tested. When both experiments 1 and 2 were compared, the coefficient of
      correlation for 16 compounds tested at the same concentrations reached 87.7%. In
      conclusion, the present study further confirms the utility of gene expression in
      HepG2 cells to identify a potential to induce PLD. Finally, based on the data
      presented, researchers are encouraged to use a range of minimum three
      concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human
      HepG2 cell line.

PMID- 17175558
TI  - Reboxetine treatment and pseudopheochromocytoma.

PMID- 17175559
TI  - Risk prediction in patients presenting with suspected cardiac pain: the GRACE and
      TIMI risk scores versus clinical evaluation.
AB  - BACKGROUND: Identifying which patients presenting with undifferentiated chest
      pain are at risk of major cardiac events is a major clinical challenge. Clinical
      evaluation may lack sufficient precision, leading to unnecessary admission or
      inappropriate discharge. It is uncertain whether risk scores derived from ACS
      populations apply to unselected patients with chest pain. AIM: To determine the
      predictive accuracies of the GRACE risk score, the TIMI risk score and clinical
      evaluation in unselected patients with suspected cardiac pain. DESIGN:
      Prospective observational study. METHODS: We recruited 347 sequential patients
      with suspected cardiac pain presenting to a large teaching hospital. The main
      outcome measures were death, non-fatal myocardial infarction and emergency
      revascularization, in hospital and at 3 months. Receiver operating characteristic
      (ROC) curves were plotted for TIMI and GRACE risk scores and clinical evaluation.
      RESULTS: Overall 54 patients (15.6%) experienced a major cardiac event (16
      deaths, seven myocardial infarctions (MIs), one emergency revascularization) or
      emergency re-admission (n=30) within 3 months. Both GRACE (p<0.001) and TIMI
      scores (p<0.001) predicted death/MI/revascularization (and the composite
      including re-admission), but the GRACE score was superior to the TIMI score for
      predicting major cardiac events (z=2.05), and both scores were superior to
      clinical evaluation (ROC areas 0.82, 0.74 and 0.55 respectively). The GRACE score
      predicted an ACS discharge diagnosis (p<0.001) and duration of hospital stay
      (p<0.001). DISCUSSION: In unselected patients presenting with suspected cardiac
      pain, the GRACE risk score is superior to the TIMI risk score in predicting major
      cardiac events, and both risk scores are superior to using ECG and troponin
      findings at presentation.

PMID- 17175560
TI  - The role of skin-homing T cells in extrinsic atopic dermatitis.
AB  - BACKGROUND: T cells that express Cutaneous Lymphocyte-Associated antigen (CLA)
      have the potential of migrating to the skin, and are hypothesized to play a role
      in cutaneous atopic disease. AIM: To investigate the immune phenotype and
      cytokine responses to Der p 1 stimulation of CLA+ T cells in extrinsic atopic
      dermatitis (EAD). DESIGN: In vitro testing, with controls. METHODS: Peripheral
      blood mononuclear cells (PBMC) were obtained from EAD patients (n=27) and non
      atopic healthy individuals (n=22). Phenotypic analysis of naive, CLA+ and non
      CLA+ memory/effector CD4+ and CD8+ T cells used markers of cell activation,
      differentiation, adhesion, apoptosis and chemokine receptor expression. Cytokine
      responses in these cells were studied following Der p 1 stimulation. RESULTS:
      CLA+ T cells from EAD patients expressed significantly higher levels of CD25, HLA
      DR, CD38, CD71, CXCR1, CXCR2 and lower levels of bcl2, CCR5, CCR7, CXCR3, and
      CD62L (p<0.05). DISCUSSION: In EAD patients, CLA+ T cells express increased
      levels of markers associated with activation, adhesion and apoptosis, show
      differences in the level of expression of differentiation markers and display a
      distinct chemokine receptor preference, compared with cells from healthy
      controls. These data suggest a significant role for CLA+ T cells in the
      pathogenesis of cutaneous atopic disease.

PMID- 17175561
TI  - The CareFile Project: a feasibility study to examine the effects of an
      individualised information booklet on patients after stroke.
AB  - INTRODUCTION: patients have reported a lack of knowledge and understanding of
      stroke and its risk factors. Uncertainty remains about the most appropriate and
      effective method of educating patients after stroke. OBJECTIVE: to assess the
      impact of the CareFile, an individualized information booklet, on patients'
      knowledge and satisfaction level after stroke. DESIGN: randomised pilot study for
      a controlled trial. SETTING: a large teaching hospital in Liverpool, UK. METHODS:
      consecutive stroke patients admitted over a 9-month period, who met the inclusion
      criteria and consented to participate, were randomised into this study. All
      patients received the usual stroke information leaflets provided by the stroke
      unit. In addition, the intervention group received the ;CareFile', a booklet
      containing general information and patient-specific information on stroke.
      Patients in both groups completed a stroke knowledge questionnaire at baseline,
      and at three and six months post-stroke. RESULTS: of the 259 admissions, 100 were
      eligible to participate, and 50 were randomised to each group. There was no
      significant difference in patient knowledge between the groups at baseline
      (P>0.05). However, at three (P<0.05) and six (P<0.005) months post-stroke, the
      intervention group had significantly better knowledge of stroke. There were no
      differences between the groups regarding satisfaction with the information
      received. CONCLUSIONS: a simple education package, in the form of an
      individualized information booklet, resulted in a significant improvement in
      knowledge and recognition of risk factors for stroke. The CareFile should make a
      valuable contribution in meeting the requirements of the National Sentinel Audit
      and National Service Framework regarding provision of information to patients
      after stroke.

PMID- 17175562
TI  - Ageing and central aortic pulse wave analysis. Commentary on "Is augmentation
      index a good measure of vascular stiffness in the elderly?" by Fantin et al.

PMID- 17175563
TI  - Influence of ageing on perioperative cardiac risk in non-cardiac surgery.
AB  - BACKGROUND: ageing is known to augment perioperative cardiac risk in non-cardiac
      surgery. However, it remains unclear whether the increased risk is attributable
      to ageing itself or to the associated cardiac risk factors and coronary artery
      disease. METHODS: this retrospective study enrolled 1,351 patients who underwent
      non-cardiac surgery after dipyridamole stress myocardial perfusion scintigraphy.
      These patients were divided into the following four groups: Group 1-E (aged 75 or
      more, normal single photon emission computed tomography (SPECT)), Group 1-Y (aged
      less than 75, normal SPECT), Group 2-E (aged 75 or more, abnormal SPECT) and
      Group 2-Y (aged less than 75, abnormal SPECT). Clinical risk factors,
      scintigraphic findings and occurrence of perioperative cardiac events were
      analysed. RESULTS: the older cohorts had a significantly higher number of risk
      factors than their younger counterparts. No significant difference was observed
      in the degree of perfusion abnormality between Groups 2-E and 2-Y. Although the
      event rates were comparable in Groups 1-E and 1-Y, Group 2-E yielded a
      significantly higher rate than Group 2-Y. Ageing was an independent predictor of
      cardiac events in Group 2 in multivariate analysis. CONCLUSIONS: ageing has no
      influence on perioperative cardiac risk in patients without overt myocardial
      infarction or ischaemia. The likelihood of cardiac events is increased by ageing,
      independently of other variables, in patients with perfusion abnormality.

PMID- 17175564
TI  - A randomised controlled trial of warfarin versus aspirin for stroke prevention in
      octogenarians with atrial fibrillation (WASPO).
AB  - BACKGROUND: atrial fibrillation (AF) is the commonest chronic arrhythmia with a
      prevalence of 9% in octogenarians and accounts for 24% of the stroke risk in this
      population. Although trials demonstrate reductions in stroke with warfarin, audit
      data show that it is still underused. However, anti-coagulation in the very
      elderly is not without risk. METHODS: randomised open labelled prospective study
      of primary thromboprophylaxis for AF. Patients aged >80 and <90 were randomised
      to receive dose-adjusted warfarin (INR 2.0-3.0) or aspirin 300 mg. All patients
      had permanent AF, were ambulant, had Folstein mini mental score >25 and had no
      contraindications to either treatment. Follow-up was for 1 year with 3 monthly
      visits. The primary outcome measure was a comparative frequency of combined
      endpoints comprising death, thromboembolism, serious bleeding and withdrawal from
      the study. RESULTS: seventy-five patients (aspirin 39; warfarin 36) were entered
      (mean age 83.9, 47% male). There were significantly more adverse events with
      aspirin (13/39; 33%) than warfarin (2/36; 6%), P = 0.002. 10/13 aspirin adverse
      events were caused by side effects and serious bleeding; there were three deaths
      (two aspirin, one warfarin). CONCLUSION: dose-adjusted warfarin was significantly
      better tolerated with fewer adverse events than aspirin 300 mg in this elderly
      population. Although aspirin 75 mg may have been better tolerated, there is no
      evidence for efficacy in AF at this dose.

PMID- 17175565
TI  - Long-term care and dementia services: an impending crisis.
AB  - BACKGROUND AND OBJECTIVES: since the transfer of long-stay care to the
      independent sector, provision of places in care homes in the United Kingdom has
      varied in response to market trends, and has shown a consistent fall in the past
      10 years. People with dementia constitute the largest diagnostic group affected
      by these changes, and are also likely to be the group that will determine future
      need. We therefore estimated the number and proportion of older residents in care
      homes who suffer from dementia relative to all those with dementia in the United
      Kingdom and projected future levels of demand on the basis of this data. DESIGN
      AND METHOD: the number of dementia cases in long-stay care was estimated from a
      random sample survey in south-east England and compared with data on age-specific
      prevalence. Projections of future demand were based on UK population projections
      for the next 40 years. MAIN RESULT: over half of all people with dementia in the
      United Kingdom are in care homes. The number of available long-stay places in
      care homes has fallen by one-sixth over the past decade. Projection of future
      demand suggests that well over double the present total places in care homes
      would be required by 2043 to maintain the present ratio of institutional to
      community services for dementia. CONCLUSION: this finding suggests an impending
      crisis of availability. A more realistic scenario calls for investment in
      affordable domiciliary care of good quality, but it will also depend on the
      acceptance of the fact that the main function of long-stay care for old people is
      now to provide for advanced cases of dementia, with consequent requirement for
      improvement in staff ratios and training.

PMID- 17175566
TI  - Sensitivity of routine system for reporting patient safety incidents in an NHS
      hospital: retrospective patient case note review.
AB  - OBJECTIVE: To evaluate the performance of a routine incident reporting system in
      identifying patient safety incidents. DESIGN: Two stage retrospective review of
      patients' case notes and analysis of data submitted to the routine incident
      reporting system on the same patients. SETTING: A large NHS hospital in England.
      POPULATION: 1006 hospital admissions between January and May 2004: surgery
      (n=311), general medicine (n=251), elderly care (n=184), orthopaedics (n=131),
      urology (n=61), and three other specialties (n=68). MAIN OUTCOME MEASURES:
      Proportion of admissions with at least one patient safety incident; proportion
      and type of patient safety incidents missed by routine incident reporting and
      case note review methods. RESULTS: 324 patient safety incidents were identified
      in 230/1006 admissions (22.9%; 95% confidence interval 20.3% to 25.5%). 270 (83%)
      patient safety incidents were identified by case note review only, 21 (7%) by the
      routine reporting system only, and 33 (10%) by both methods. 110 admissions
      (10.9%; 9.0% to 12.8%) had at least one patient safety incident resulting in
      patient harm, all of which were detected by the case note review and six (5%) by
      the reporting system. CONCLUSION: The routine incident reporting system may be
      poor at identifying patient safety incidents, particularly those resulting in
      harm. Structured case note review may have a useful role in surveillance of
      routine incident reporting and associated quality improvement programmes.

PMID- 17175567
TI  - IQ in childhood and vegetarianism in adulthood: 1970 British cohort study.
AB  - OBJECTIVE: To examine the relation between IQ in childhood and vegetarianism in
      adulthood. DESIGN: Prospective cohort study in which IQ was assessed by tests of
      mental ability at age 10 years and vegetarianism by self-report at age 30 years.
      SETTING: Great Britain. PARTICIPANTS: 8170 men and women aged 30 years
      participating in the 1970 British cohort study, a national birth cohort. MAIN
      OUTCOME MEASURES: Self-reported vegetarianism and type of diet followed. RESULTS:
      366 (4.5%) participants said they were vegetarian, although 123 (33.6%) admitted
      eating fish or chicken. Vegetarians were more likely to be female, to be of
      higher social class (both in childhood and currently), and to have attained
      higher academic or vocational qualifications, although these socioeconomic
      advantages were not reflected in their income. Higher IQ at age 10 years was
      associated with an increased likelihood of being vegetarian at age 30 (odds ratio
      for one standard deviation increase in childhood IQ score 1.38, 95% confidence
      interval 1.24 to 1.53). IQ remained a statistically significant predictor of
      being vegetarian as an adult after adjustment for social class (both in childhood
      and currently), academic or vocational qualifications, and sex (1.20, 1.06 to
      1.36). Exclusion of those who said they were vegetarian but ate fish or chicken
      had little effect on the strength of this association. CONCLUSION: Higher scores
      for IQ in childhood are associated with an increased likelihood of being a
      vegetarian as an adult.

PMID- 17175570
TI  - Referral trends in mental health services for adults with intellectual disability
      and autism spectrum disorders.
AB  - Researchers have paid increasing attention to mental health issues in adults with
      autism spectrum disorders (ASDs) over the last decades. However, little is known
      about how rates of clinical referrals, types of mental health diagnoses and
      treatment in adults with ASDs and intellectual disability have changed. We
      examined patterns of change in referral trends to specialist mental health
      services in south London from 1983 to 2000 (N = 137). The majority of the cases
      (58.4%) did not have a diagnosable psychiatric disorder. Schizophrenia was the
      most frequent psychiatric diagnosis followed by depression, adjustment reaction
      and anxiety. There was a significant change in the rate of referrals, an increase
      in the diagnosable psychiatric disorders over time and a significant reduction of
      medication at time of referral. There were no significant changes in the use of
      other therapeutic interventions. The proportion of participants living
      independently increased. Implications for services and future research are
      discussed.

PMID- 17175571
TI  - Tics and Tourette syndrome in autism spectrum disorders.
AB  - Autism spectrum disorders (ASDs) are more frequently associated with tic
      disorders than expected by chance. Variable rates of comorbidity have been
      reported and common genetic and neurobiological factors are probably involved.
      The aim of this study was to determine the rate of tic disorders in a clinical
      sample (n = 105) of children and adolescents with ASDs and to describe the
      clinical characteristics of a group with comorbid ASDs and tics (n = 24). The
      overlap between tics and other repetitive movements and behaviors in ASDs was
      carefully assessed. Among individuals with ASDs, 22 percent presented tic
      disorders: 11 percent with Tourette disorder (TD), and 11 percent with chronic
      motor tics. All had various degrees of cognitive impairment. An association
      between the level of mental retardation and tic severity was found. It is
      concluded that the occurrence of tics in ASDs should not be overlooked and should
      be carefully evaluated.

PMID- 17175568
TI  - Comparison of treatment effects between animal experiments and clinical trials:
      systematic review.
AB  - OBJECTIVE: To examine concordance between treatment effects in animal experiments
      and clinical trials. Study design Systematic review. DATA SOURCES: Medline,
      Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS. STUDY SELECTION: Animal
      studies for interventions with unambiguous evidence of a treatment effect
      (benefit or harm) in clinical trials: head injury, antifibrinolytics in
      haemorrhage, thrombolysis in acute ischaemic stroke, tirilazad in acute ischaemic
      stroke, antenatal corticosteroids to prevent neonatal respiratory distress
      syndrome, and bisphosphonates to treat osteoporosis. Review methods Data were
      extracted on study design, allocation concealment, number of randomised animals,
      type of model, intervention, and outcome. RESULTS: Corticosteroids did not show
      any benefit in clinical trials of treatment for head injury but did show a
      benefit in animal models (pooled odds ratio for adverse functional outcome 0.58,
      95% confidence interval 0.41 to 0.83). Antifibrinolytics reduced bleeding in
      clinical trials but the data were inconclusive in animal models. Thrombolysis
      improved outcome in patients with ischaemic stroke. In animal models, tissue
      plasminogen activator reduced infarct volume by 24% (95% confidence interval 20%
      to 28%) and improved neurobehavioural scores by 23% (17% to 29%). Tirilazad was
      associated with a worse outcome in patients with ischaemic stroke. In animal
      models, tirilazad reduced infarct volume by 29% (21% to 37%) and improved
      neurobehavioural scores by 48% (29% to 67%). Antenatal corticosteroids reduced
      respiratory distress and mortality in neonates whereas in animal models
      respiratory distress was reduced but the effect on mortality was inconclusive
      (odds ratio 4.2, 95% confidence interval 0.85 to 20.9). Bisphosphonates increased
      bone mineral density in patients with osteoporosis. In animal models the
      bisphosphonate alendronate increased bone mineral density compared with placebo
      by 11.0% (95% confidence interval 9.2% to 12.9%) in the combined results for the
      hip region. The corresponding treatment effect in the lumbar spine was 8.5% (5.8%
      to 11.2%) and in the combined results for the forearms (baboons only) was 1.7% (
      1.4% to 4.7%). CONCLUSIONS: Discordance between animal and human studies may be
      due to bias or to the failure of animal models to mimic clinical disease
      adequately.

PMID- 17175572
TI  - A placebo double-blind pilot study of dextromethorphan for problematic behaviors
      in children with autism.
AB  - We used a mixed group/single-case, double-blind, placebo-controlled, ABAB design
      to examine the safety and efficacy of the glutamate antagonist dextromethorphan
      for the treatment of problematic behaviors and core symptoms in eight children
      diagnosed with autism. All participants had increased levels of irritability at
      baseline as measured by the Aberrant Behavior Checklist, and demonstrated a wide
      variety of problematic behaviors. Group analyses revealed that dextromethorphan
      was equivalent to placebo in the treatment of problem behaviors and core
      symptoms. Analyses at the single-subject level demonstrated that three of the
      eight participants who had a behavioral profile consistent with attention-deficit
      hyperactivity disorder responded positively to dextromethorphan. Future research
      that employs a larger, more homogeneous sample is necessary to replicate the
      findings from this study.

PMID- 17175573
TI  - Social services support and expenditure for children with autism.
AB  - This article provides information about children with autism who are supported by
      English social services departments based on the Children in Need Survey 2001
      (CIN2001). In 119 authorities, 6310 children were recorded as having a diagnosis
      of autism or related conditions, probably about one-quarter of all children with
      such diagnoses and about half of those actually supported. Demographically, this
      group appears similar to children with autism generally: there are more boys than
      girls, and learning, communication and behaviour difficulties are common. CIN2001
      shows that mean social services support costs tend to be quite high, particularly
      compared with other disabled children. There are very considerable variations
      between social services departments in reported numbers and spending. It is
      unlikely that this variation can be attributed to the prevalence of autism, and
      more likely that it reflects the case recognition and service provision policies
      of local agencies.

PMID- 17175574
TI  - A pilot study of the effects of a social-pragmatic intervention on the
      communication and symbolic play of children with autism.
AB  - The acquisition of social communication skills is a major challenge faced by
      children with autism. This pilot study investigated the effects of the Stronger
      Families Project, a social-pragmatic intervention, on the communication and
      symbolic abilities of 16 children aged 2-4 years with autism. Standardized
      measures of the child's communication and symbolic behaviour were conducted by
      independent observers at a university clinic pre and post-intervention, and
      parents were interviewed to determine the impact of variables such as maternal
      stress and competence on the child's social communication. Changes in some
      communication and symbolic behaviours occurred following the Stronger Families
      Project intervention according to parent report. However, improvements based on
      ratings by independent observers were not significant. Results are discussed in
      relation to the assessment of changes in the social communication and symbolic
      play of children with autism following intervention using clinical observation
      and parent report.

PMID- 17175575
TI  - Evaluation of hearing in children with autism by using TEOAE and ABR.
AB  - Assessment of auditory abilities is important in the diagnosis and treatment of
      children with autism. The aim was to evaluate hearing objectively by using
      transient evoked otoacoustic emission (TEOAE) and auditory brainstem response
      (ABR). Tests were performed on 30 children with autism and 15 typically
      developing children, following otomicroscopy and tympanometry. The children with
      autism were sedated before the tests. Positive emissions and normal hearing level
      at ABR were obtained in both ears of all children in the control group and of 25
      children with autism. TEOAE and ABR results varied in the remaining five children
      with autism. The mean III-V interpeak latencies (IPLs) in both ears of children
      with autism were longer than those in the control group. Hearing loss may be more
      common in children with autism than in typically developing children.

PMID- 17175576
TI  - Disembedding performance in children and adolescents with Asperger syndrome or
      high-functioning autism.
AB  - The aim of the present study was to assess the findings, reported in earlier
      studies, that individuals with autism spectrum disorders process visuo-spatial
      tasks faster than typically developing control persons. The participants in the
      present study were children and adolescents with Asperger syndrome (AS) or high
      functioning autism (HFA) (N = 13), and a matched group of typically developing
      children and adolescents (N = 13). The results showed that the participants in
      the clinical group performed marginally less well than those in the control group
      on both the Block Design Test and the Embedded Figures Test, but the differences
      were not statistically significant. Thus, earlier findings suggesting that
      individuals with autism spectrum disorders solve non-social cognitive tasks
      faster than typically developing control persons were not replicated. The results
      are discussed with special reference to the hypothesis of weak central coherence.

PMID- 17175578
TI  - Separation-survivability-the elusive moral cut-off point?

PMID- 17175577
TI  - Fluid therapy for children: facts, fashions and questions.
AB  - Fluid therapy restores circulation by expanding extracellular fluid. However, a
      dispute has arisen regarding the nature of intravenous therapy for acutely ill
      children following the development of acute hyponatraemia from overuse of
      hypotonic saline. The foundation on which correct maintenance fluid therapy is
      built is examined and the difference between maintenance fluid therapy and
      restoration or replenishment fluid therapy for reduction in extracellular fluid
      volume is delineated. Changing practices and the basic physiology of
      extracellular fluid are discussed. Some propose changing the definition of
      "maintenance therapy" and recommend isotonic saline be used as maintenance and
      restoration therapy in undefined amounts leading to excess intravenous sodium
      chloride intake. Intravenous fluid therapy for children with volume depletion
      should first restore extracellular volume with measured infusions of isotonic
      saline followed by defined, appropriate maintenance therapy to replace
      physiological losses according to principles established 50 years ago.

PMID- 17175579
TI  - Converting inactive peptides into potent transcriptional activators.
AB  - Significant efforts have been devoted to the development of artificial
      transcriptional activators for use as mechanistic tools, as therapeutic agents,
      and for biomanufacturing applications. One of the primary challenges has been the
      development of artificial activators that exhibit potency in cells comparable to
      that of endogenous activators; the vast majority function only moderately in the
      cellular context. Here we demonstrate that the superimposition of two distinct
      binding modes, a masking interaction and an interaction with the transcriptional
      machinery, has a profoundly positive effect on the cellular activity of
      artificial activators, with up to 600-fold enhancement observed. Incorporation of
      this feature into future generations of small molecule transcriptional activators
      should increase their nuclear uptake and facilitate their accessibility to their
      target proteins, thus significantly augmenting both their activity and utility.

PMID- 17175580
TI  - A comparative study of bioorthogonal reactions with azides.
AB  - Detection of metabolites and post-translational modifications can be achieved
      using the azide as a bioorthogonal chemical reporter. Once introduced into target
      biomolecules, either metabolically or through chemical modification, the azide
      can be tagged with probes using one of three highly selective reactions: the
      Staudinger ligation, the Cu(I)-catalyzed azide-alkyne cycloaddition, or the
      strain-promoted [3 + 2] cycloaddition. Here, we compared these chemistries in the
      context of various biological applications, including labeling of biomolecules in
      complex lysates and on live cell surfaces. The Cu(I)-catalyzed reaction was found
      to be most efficient for detecting azides in protein samples but was not
      compatible with live cells due to the toxicity of the reagents. Both the
      Staudinger ligation and the strain-promoted [3 + 2] cycloaddition using optimized
      cyclooctynes were effective for tagging azides on live cells. The best reagent
      for this application was dependent upon the specific structure of the azide.
      These results provide a guide for biologists in choosing a suitable ligation
      chemistry.

PMID- 17175581
TI  - Current awareness in prenatal diagnosis.

PMID- 17175582
TI  - Compromised pulmonary artery catheter injection following sternal retraction.

PMID- 17175583
TI  - Absorption of lipopolysaccharide from the intestine during aortic cross-clamping
      in humans.

PMID- 17175584
TI  - [Case report of partial denture using Dimple-bar telescopic system].
AB  - PATIENT: A 49-year-old female patient presented to Prosthodontic Clinic at Nihon
      University School of Dentistry at Matsudo with the chief complaints of chewing
      difficulty and poor appearance. She was diagnosed moderate to severe
      periodontitis and partially edentulous dentition on both maxilla and mandible.
      Occlusal reconstruction was conducted with crown restorations and removable
      partial dentures (RPD). From the esthetic request of patient, Dimple-bar
      telescopic (DBT) system was applied to the mandible with bilateral distal coping
      abutments. DISCUSSION: DBT system has been functioning well for more than 5 years
      without abutment tooth loss. It was thought that bilateral distal coping
      abutments can help to resolve problem with bilateral distal extension RPD
      dilemma. CONCLUSION: It is suggested that DBT system has great potential to
      resolving weak points of clasps, such as low retentive forces and/or esthetic
      problem. Furthermore, author got a new understanding of the importance of
      maintenances.

PMID- 17175585
TI  - [Case report of prosthetic treatment for defected jaw with enucleation of the
      right maxillary sinus tumor].
AB  - PATIENT: The patient is a 71-year-old woman who had undergone a gingivectomy due
      to a gingival carcinoma of right maxillary sinus and a denture was made for the
      defected jaw. DISCUSSION: During three years and six months, |3 serves as the
      guidance tooth had suffered from various symptoms, from the detachment of the
      neighboring tooth to the use of an OP anchor followed by a partial fracture of
      the cuspid root. However, |3 has not been removed in accordance to the patient's
      request. In addition, a relining provided indirectly to the denture, it is still
      maintained and used for mastication, pronunciation and swallowing functions
      without difficulty. CONCLUSION: This is a case that a denture was made for the
      defected jaw. However, it is important ot take measures in the future, as the
      remaining tooth is not expected to be preserved for long.

PMID- 17175586
TI  - [Case of complete denture with improvement of facial aspect through the recovery
      of the mandibular position].
AB  - PATIENT: This is a clinical case report of esthetic and masticatory impairment
      due to a mandibular protrusion during occlusion. The patient was a complete
      edentulous subject who complained about esthetic and matiscatory disturbance.
      First of all, treatment dentures were done, in order to improve the mandible
      position and recover the facial aspect. Objective evaluations were carried out to
      compare the improvements achieved after the insertion of the new dentures.
      DISCUSSION: The treatment dentures were used to improve patient's mandible
      position as well as vertical dimension. Once the facial appearance was recovered
      as a result of an appropriate mandible position, a reduction of the angle formed
      between the FH plane and the A-B plane from 87 to 83 was recognized after the
      insertion of the new dentures through the analysis of lateral cephalograms. It
      indicates that the mandible's position changed to backward position resulting in
      an improvement of the facial aspect. CONCLUSION: In the present clinical case
      report, not only subjective evaluation for appropriate mandible position and
      vertical dimension, but also including objective evaluation methods allowed us to
      evaluate and compare objectively the patient's pre and post operative condition.

PMID- 17175587
TI  - [Case of oral lichen planus due to dental metal allergy].
AB  - PATIENT: This clinical report describes the treatment of a patient who
      experienced a hypersensitivity reaction associated with prosthetic restorations
      fabricated with a silver-palladium-copper-gold alloy. DISCUSSION: Patch testing
      revealed an allergy to the palladium substrate. Allergic symptoms disappeared
      from the patient's mucous membrane after all the prosthetic restorations in the
      patient were replaced with those fabricated using some alternative alloys. The
      case presented indicates that the release of palladium from prosthesis fabricated
      with dental metal alloys is able to induce hypersensitivity reactions resulting
      in soft-tissue changes in the buccal mucosa. CONCLUSION: Dental procedures as a
      multidisciplinary approach to the care taking of patient are presented.

PMID- 17175588
TI  - [A study on the effect of Oncomelania hupensis hupensiss killed with niclosamide
      in China].
AB  - OBJECTIVE: To study the effect of Oncomelania hupensis hupensis of niclosamide,
      and exploring the main influencing factors. METHODS: The samples of Oncomelania
      hupensis hupensis were collected from 37 sampling sites in 33 counties of 10
      provinces by means of stratified random sampling methods in accordance with the
      categories of Oncomelania hupensis hupensis habitats. Samples were randomly
      located into study group and control group. Oncomelania hupensis hupensis of the
      study group was marinated in different concentration liquor of niclosamide which
      was confected with water for 24 hours or 48 hours, then LC50 of niclosamide by
      which Oncomelania hupensis hupensis was killed and amount calculated. The
      influencing factors of the mortality of Oncomelania hupensis hupensis in the
      study group was statistically analyzed by 2 test and by multiple logistic
      regression using SPSS 13.0 statistical software. RESULTS: The mortality of
      Oncomelania hupensis hupensis of the two test groups which were marinated in 0.5
      mg/L liquor for 48 hours and 1.0 mg/L liquor for 24 hours was 100%. The effect of
      Oncomelania hupensis hupensis killed by niclosamide was markedly reduced along
      with the reduction of drug concentration. The average LC50 rates of niclosamide
      liquor by which Oncomelania hupensis hupensis killed for the 24 hours and 48
      hours in the study group, were 0.0939 mg/L and 0.0625 mg/L, respectively. There
      was significant difference between the two test groups (chi(2) = 5.001, P <0.01)
      . In determinate range of concentration, the mortality of Oncomelania hupensis
      hupensis showed significant difference among the geographic types of habitat (
      chi(2) = 4.264, P < 0.05). By means of multiple logistic regression using SPSS
      13.0 statistical software, the estimate value of coefficient of regression on the
      influence factors, drug concentration, test time and the geographic types of
      habitat were 2. 047 ( OR = 5. 573), 0.263 ( OR = 2.924) and 0. 187- 0.210 ( OR =
      1.969- 2. 560), respectively. CONCLUSION: Niclosamide could kill Oncomelania
      hupensis hupensis effectively. The main influencing factors on the efficacy of
      niclosamide by which Oncomelania hupensis hupensis was killed, appeared to be
      drug concentration, time of testing and the geographic types of habitat.

PMID- 17175589
TI  - The staging of lymphoedema and accompanying symptoms.
AB  - Community nurses are recognized as potentially having a much greater role to play
      in identifying, referring and helping in the long-term management of lymphoedema.
      This will require knowledge of all stages of the diagnostic and treatment
      process. In this article, the author discusses staging, or the assessment of the
      severity of the disease. Staging can be useful not only in deciding the best
      course of treatment for the individual, but also in measuring the progress of
      treatment.

PMID- 17175590
TI  - Assessment of lymphoedema of the lower limbs by the community nurse.
AB  - Community nurses are increasingly at the frontline in supporting patients in the
      management of long-term conditions. They are therefore likely to be involved in
      identifying and providing care for people who are affected by lymphoedema.
      Community practitioners will need to develop the skills to recognize patients who
      have, or are at risk for developing, lymphoedema. Aspects of the nursing
      assessment of lymphoedema include taking a detailed history and conducting a
      comprehensive physical and psychosocial assessment of the impact of this
      condition. The assessment is multifaceted and will often require intervention
      from other members of the multidisciplinary team.

PMID- 17175591
TI  - Living with lymphoedema in Essex. Interview by Tom Pollard.

PMID- 17175592
TI  - Mixed lymphovenous oedema with leg ulceration: a case study.
AB  - Necrotizing skin infections, although rare, have proven difficult to manage and
      treat in a wide range of patient groups. The risks of extensive tissue necrosis,
      systemic sepsis and potentially organ failure make this disease one which health
      care professionals must be aware of. Treatment involves rapid debridement and
      intensive therapy including broad-spectrum antibiotics. Appropriate wound care is
      essential as is a great deal of psychological support for the patient and
      relatives. This article also highlights some of the risk factors which may pre
      dispose a patient to infection.

PMID- 17175593
TI  - An update on the Lymphoedema Framework Project.

PMID- 17175594
TI  - Findings of research misconduct.

PMID- 17175595
TI  - Descriptive epidemiology of enteric illness for selected reportable diseases in
      Ontario, 2003.

PMID- 17175596
TI  - Medical morals: an exchange.

PMID- 17175597
TI  - Changes of opportunistic infection pattern in patients with AIDS in Jakarta.

PMID- 17175598
TI  - Descriptive analysis of endemic and travel hepatitis A cases in Ontario, 1998 to
      2004.

PMID- 17175599
TI  - Health hazard alerts. Suspected tampering associated with various ham and sliced
      meat products. Canadian Food Inspection Agency, Ottawa, Ontario.

PMID- 17175600
TI  - Opportunistic infection of HIV-infected/AIDS patients in Indonesia: problems and
      challenge.
AB  - Infectious diseases are one of the biggest health-problem in the world, while
      HIV/AIDS itself ranks second in mortality. The latest situation shows a
      remarkable increase of HIV/AIDS cases in Indonesia. About 90.000 to 130.000
      people in Indonesia are predicted of being infected with HIV nowadays. HIV may
      progress to AIDS as patient's immune status decreases. As well to the condition,
      opportunistic infections will occur and eventually it may lead to death. An
      efficient and effective approach in early detection and proper management of
      opportunistic infections, followed with sufficient anti retroviral
      administration, may reduce mortality. Other approaches in managing HIV/AIDS and
      opportunistic infections are needed to support a complete and holistic management
      for patients with HIV. Full participation from family, medical experts,
      government and public is strictly a must to overcome this problem.

PMID- 17175601
TI  - Clinical approach and management of food poisoning.
AB  - Food poisoning may occur in a group of people or a single person. The symptoms
      caused by food poisoning are varied from mild to severe or even fatal one such as
      death. Immunocompromised patients and others such as elderly and children are
      susceptible for food poisoning. Re-hydration is the main key in the management of
      food poisoning. Empirical therapy using antibiotics may be considered in high
      risk patients such as elderly, immunocompromised, diabetes, liver cirrhosis or
      intestinal hypomotility. Prevention is an important measure in management of food
      poisoning by keeping the food from contamination, always fresh and maintaining
      good hygiene.

PMID- 17175602
TI  - Global distribution of measles and rubella genotypes--update.

PMID- 17175604
TI  - 35 Years--a history of AJO:true to its core mission.

PMID- 17175603
TI  - Influenza.

PMID- 17175605
TI  - Personal narrative of prof. Reuben Eldar, Laureate of Croatian National
      Decoration for Humanitarian Work.

PMID- 17175606
TI  - Personal narrative of prof. Zeljko Bosnjak, Laureate of Croatian National
      Decoration for Humanitarian Work.

PMID- 17175607
TI  - Toward a life span developmental psychopathology perspective on bipolar disorder.

PMID- 17175608
TI  - Metabolic syndrome and cardiovascular disease.

PMID- 17175609
TI  - Just a minute.

PMID- 17175610
TI  - [Patient information. Toxic hepatitis].

PMID- 17175611
TI  - The relationship between shoulder alignment and elbow joint angle in cricket fast
      medium bowlers.
AB  - The aim of this study was to examine the relationship between shoulder alignment
      and elbow angle during the delivery action of fast-medium bowlers. The elbow and
      upper trunk alignment were recorded for 13 high-performance bowlers (mean age 20
      years) using a 12-camera Vicon motion analysis system operating at 250 Hz. The
      three highest velocity trials for "good" and "short" length deliveries were
      analysed. Results showed that bowlers with a more front-on shoulder alignment at
      back-foot impact and when the upper arm was horizontal to the ground experienced
      a significantly greater elbow flexion--extension range when compared with those
      who had a more side-on orientation at the same point in the delivery action.
      Bowlers with greater shoulder counter-rotation also recorded higher elbow flexion
      and subsequently extension during the period from upper arm horizontal to ball
      release. Shoulder alignment and elbow angles were similar for "short" and "good"
      length deliveries. It was concluded that bowlers with a more front-on shoulder
      orientation at back-foot impact demonstrated a higher elbow extension from upper
      arm horizontal to ball release and are therefore more likely to infringe
      International Cricket Council elbow tolerance levels, compared with those who
      adopt a more side-on shoulder orientation at back-foot impact.

PMID- 17175612
TI  - Low-dose exercise training does not influence cardiac autonomic control in
      healthy sedentary men aged 55-75 years.
AB  - The purpose of this study was to evaluate the effects of a realistic, feasible,
      and commonly used fitness training programme on cardiac autonomic control in 14
      sedentary men aged 62.0 +/- 6.1 years (mean +/- s). All participants performed a
      one-year fitness training programme in which training intensity and frequency
      were specifically chosen to be compliant for the majority of the participants (2
      3 sessions per week at moderate intensity). At the same time, a reference group
      consisting of 15 sedentary age-matched men (age 64.2 +/- 6.5 years) did not
      change their habitual physical activity. Measurements were performed before and
      after the training intervention. Cardiac autonomic control was inferred from
      resting values (supine and standing) of heart rate variability (HRV) computed in
      the frequency domain over 10-min intervals. Endurance capacity was evaluated
      during a maximal incremental bicycle ergometer test. In spite of an increase in
      peak oxygen consumption (VO2peak) by 6.4% after training, heart rate in the
      training group remained unchanged at rest and at the same metabolic demand. No
      changes in resting parameters of HRV were shown for either groups or positions.
      Results from this study provide no evidence of a clinically meaningful increase
      in the vagal modulation to the sinus node at rest after one year of low-volume
      and moderate-intensity fitness training in men aged 55-75 years.

PMID- 17175613
TI  - Success in elite cycling: A prospective and retrospective analysis of race
      results.
AB  - The development of peak performances is a main research focus in sports science.
      It is unclear how many former top junior athletes achieve success in the elite
      class later. The aim of the present study was to examine the careers of athletes
      who participated in major junior or adult/elite cycling events using prospective
      and retrospective analysis of competition results. The official results of major
      junior (age < or = 18 years) and elite (age > 18 years) cycling races from 1980
      to 2004 were analysed. Age-related aspects, career lengths, and success were
      compared between riders who presented results in both junior and elite races
      (JUNIOR ELITE) and riders who had no junior race results (ELITE ONLY).
      Altogether, 27,454 results of 8004 athletes from 108 countries were collected. We
      found that 29.4% of the elite athletes had participated in junior World
      Championships, and that 34% of the participants in junior World Championships
      later participated in major elite competitions. JUNIOR ELITE athletes are
      significantly more successful in several cycling disciplines and have their first
      and last elite result at a younger age than ELITE ONLY athletes. No difference
      was found in career lengths. The data presented here emphasize the importance of
      long-term training programmes in the development of peak performance in cycling.

PMID- 17175614
TI  - Exhaled nitric oxide in single and repetitive prolonged exercise.
AB  - This study was performed to determine the influence of single and repetitive
      exercise on nitric oxide (NO) concentration in the lung. Exhaled NO concentration
      (FE(NO)) was measured during a constant-flow exhalation manoeuvre (170 ml x s(
      1), against a 10 cmH2O resistance) in healthy individuals (a) during and after a
      100-min square-wave exercise of between 25 and 60% of maximal power output (n =
      18) and (b) before and after five successive prolonged exercises (90-120 min, 75
      85% of maximal heart rate) separated by 48 or 24 h (n = 8). The FE(NO0.170) was
      decreased during and after the 100-min exercise test (mean +/- s(x): 58.5 +/-
      3.7% and 76.7 +/- 5.2% of resting value at 90 min of exercise and 15 min post
      exercise, respectively; P < 0.05). The five successive exercise sessions induced
      a similar post-exercise FE(NO0.170) decrement (73.1 +/- 2.9% of resting value 15
      min post-exercise), while basal FE(NO0.170) values were not different between the
      five sessions (P > 0.05). These results suggest that prolonged exercise induces a
      reduction in NO concentration within the lung that lasts for several minutes
      after the end of exercise. However, repetitive exercises (at least every 24 h)
      allow complete NO recovery from one session to another. The implication of such a
      decrease in NO availability within the lung remains to be clarified.

PMID- 17175615
TI  - The influence of game duration and playing position on intensity of exercise
      during match-play in elite water polo players.
AB  - In this study, we assessed exercise intensity in 20 water polo games of different
      duration. The hypothesis that right wing players perform at a higher intensity
      than back and forward central players was also tested. Thirty water polo players,
      equally split between three field positions, participated in the study.
      Initially, their performance-related physiological capabilities were evaluated.
      Subsequently, during water polo games of short (4 x 7-min periods) or long
      duration (4 x 9-min periods), heart rate was monitored continuously and blood
      lactate concentration was measured at the end of each period. Activity patterns
      were also recorded using a video camera. Mean heart rate over the entire game was
      156 +/- 18 beats x min(-1). Overall exercise intensity fluctuated around a value
      corresponding to the lactate threshold (4.03 +/- 0.96 mmol x l(-1), 86 +/- 5% of
      peak heart rate) and decreased (P < 0.003) with game time (4.22 +/- 1.8 and 3.47
      +/- 1.9 mmol x l(-1) in the second and fourth quarter, respectively). During the
      last 6 min, heart rate was higher (P < 0.001) in games of short duration (156 +/-
      3 beats x min(-1)) than in games of long duration (152 +/- 8 beats x min(-1)).
      Video analysis showed that the percentage of time spent in low-intensity
      activities (i.e. "out of game") was lower (23 vs. 26%), whereas that in high
      intensity activities (i.e. "sprinting crawl") was higher (21 vs. 19%), in games
      of short compared with long duration. No difference was observed among players of
      various field positions in any of the variables examined. Thus during match-play,
      games of long duration produced significantly lower heart rate responses than
      games of short duration, and the physiological response exhibited by the players
      was not affected by field position. The water polo authorities should consider
      these results before changing game duration and coaches should prepare their
      athletes accordingly.

PMID- 17175616
TI  - Comparison of kinematics in skilled and unskilled arms of the same recreational
      baseball players.
AB  - We examined mechanisms of coordination that enable skilled recreational baseball
      players to make fast overarm throws with their skilled arm and which are absent
      or rudimentary in their unskilled arm. Arm segment angular kinematics in three
      dimensions at 1000 Hz were recorded with the search-coil technique from the arms
      of eight individuals who on one occasion threw with their skilled right arm and
      on another with their unskilled left arm. Compared with their unskilled arm, the
      skilled arm had: a larger angular deceleration of the upper arm in space in the
      forward horizontal direction; a larger shoulder internal rotation velocity at
      ball release (unskilled arms had a negative velocity); a period of elbow
      extension deceleration before ball release; and an increase in wrist velocity
      with an increase in ball speed. It is suggested that some of these differences in
      arm kinematics occur because of differences between the skilled and unskilled
      arms in their ability to control interaction torques (the passive torque at one
      joint due to motion at adjacent joints). It is proposed that one reason unskilled
      individuals cannot throw fast is that, unlike their skilled counterparts, they
      have not developed the coordination mechanisms to effectively exploit interaction
      torques.

PMID- 17175617
TI  - Muscle oxygenation and EMG activity during isometric exercise in children.
AB  - The aim of this study was to examine the time-course of and the relationships
      between muscle oxygenation, blood volume and myoelectrical manifestations during
      isometric exercise in children. Twelve healthy children aged 12.5 +/- 1.2 years
      (mean +/- s) performed an isometric knee extension at 50% of their maximal
      voluntary contraction (MVC) until exhaustion to assess endurance time (limit
      time, T(lim)). Changes in muscle oxygenation and blood volume were assessed by
      near infrared spectroscopy (NIRS). The root mean square (RMS) amplitude and the
      mean power frequency (MPF) from electromyogram (EMG) signals were obtained, as
      NIRS parameters, from the vastus lateralis. Mean T(lim) was 117 +/- 34 s. The
      muscle oxygenation and blood volume curves decreased immediately at the beginning
      of exercise. Maximal deoxygenation occurred at 50% T(lim), and fell by 76.9% from
      the resting value. Similarly, minimal blood volume was observed at 50% T(lim); it
      reached a plateau that lasted until the end of exercise. The kinetics of the MPF
      and RMS curves were inversely related to time. At the last set of exercises
      (after 75% T(lim)), a steeper RMS curve and an abrupt decrease in the MPF curve
      were observed. Significant correlations (r) between muscle oxygenation, blood
      volume, root mean square amplitude and mean power frequency were observed, which
      ranged from 0.72 to 0.99. These findings suggest that the fatigue resulting from
      sustained isometric exercise is related to a decrease in oxygenation and blood
      volume.

PMID- 17175618
TI  - Proud flesh: the cult of cosmetic surgery.

PMID- 17175619
TI  - The role of guidelines in managing diseases.

PMID- 17175620
TI  - Improving the treatment of rheumatoid arthritis.

PMID- 17175621
TI  - The burden of chronic insomnia on society.

PMID- 17175622
TI  - I am emergency medicine.

PMID- 17175623
TI  - Management and outcomes of pediatric patients transported by emergency medical
      services in a Canadian prehospital system.
AB  - OBJECTIVES: There is uncertainty around the types of interventions that are
      provided by emergency medical services (EMS) to children during prehospital
      transport. We describe the patient characteristics, events, interventions
      provided and outcomes of a cohort of children transported by EMS. METHODS: This
      prospective cohort study was conducted in a city of 750 000 people with a 2
      tiered EMS system. All children <16 years of age who were attended by EMS during
      a 6-month period were enrolled. Data were extracted from ambulance call reports
      and hospital charts, and analyzed using descriptive statistics. RESULTS: During
      the study period there were 1377 pediatric EMS calls. Mean age was 8.2 years
      (standard deviation 5.4), and the most Common diagnoses were trauma (44.9%),
      seizure (11.8%) and respiratory distress (8.8%). The ambulance return code was
      Urgent in 7%, Prompt in 57%, Deferrable in 8% and Not Transported in 28%. Fifty
      six percent received either an Advanced Life Support or Basic Life Support
      prehospital intervention. Common procedures included cardiac monitoring (20.0%),
      oxygen administration (19.8%), blood glucose monitoring (16.3%), spine board
      (12.2%), limb immobilization (11.1%) and cervical collar (10.0%). Uncommon
      procedures included administering medications intravenously (IV) (1.4%), bag
      valve-mask ventilation (0.3%) and endotracheal intubation (0.1%). Seventy-eight
      percent of attempted IV lines were successful. Only 9.0% of EMS-transported
      children were admitted to hospital, and 2.2% were admitted to the intensive care
      unit. CONCLUSIONS: This first study of Canadian pediatric prehospital
      interventions shows a high rate of non-transport, and a low rate of Urgent
      transports and hospital admissions for children. Very few children receive
      prehospital airway management, ventilation or IV medications; consequently EMS
      personnel have little opportunity to maintain these pediatric skills in the
      field.

PMID- 17175624
TI  - Ability of neuron-specific enolase to predict survival to hospital discharge
      after successful cardiopulmonary resuscitation.
AB  - BACKGROUND: Accurate prediction of survival to hospital discharge in patients who
      achieve return of spontaneous circulation after cardiopulmonary resuscitation
      (CPR) has significant ethical and socioeconomic implications. We investigated the
      prognostic performance of serum neuron-specific enolase (NSE), a biochemical
      marker of ischemic brain injury, after successful CPR. METHODS: In-hospital or
      out-of-hospital patients with nontraumatic normothermic cardiac arrest who
      achieved return of spontaneous circulation (ROSC) following at least 5 minutes of
      CPR were eligible. Neuron-specific enolase levels were assessed immediately, 6
      hours, 12 hours and 2 days after ROSC. Subjects were followed to death or
      hospital discharge. RESULTS: Seventeen patients (7 men, 10 women) were enrolled
      during a 1-year period. Median (range) NSE levels in survivors and non-survivors
      respectively were as follows: immediately after ROSC: 14.0 microg/L (9.1-51.4
      microg/L) versus 25.9 microg/L (10.2-57.5 microg/L); 6 hours after ROSC: 15.2
      microg/L (9.7-30.8 microg/L) versus 25.6 microg/L (12.7-38.2 microg/L); 12 hours
      after ROSC: 14.0 microg/L (8.6-32.4 microg/L) versus 28.5 microg/L (11.0-50.7
      microg/L); and 48 hours after ROSC: 13.1 microg/L (7.8-29.5 microg/L) versus 52.0
      microg/L (29.1-254.0 microg/L). Non-survivors had significantly higher NSE levels
      48 hours after ROSC than surivors (p = 0.04) and showed a trend toward higher
      values during the entire time course following ROSC. An NSE concentration of >30
      microg/L 48 hours after ROSC predicted death with a high specificity (100%: 95%
      confidence interval [CI] 85%-100%), and a level of 29 microg/L or less at 48
      hours predicted survival with a high specificity (100%: 95% CI 83%-100%).
      CONCLUSIONS: Serum NSE levels may have clinical utility for the prediction of
      survival to hospital discharge in patients after ROSC following CPR over 5
      minutes in duration. This study is small, and our results are limited by wide
      confidence intervals. Further research on ability of NSE to facilitate prediction
      and clinical decision-making after cardiac arrest is warranted.

PMID- 17175625
TI  - Understanding receiver operating characteristic (ROC) curves.

PMID- 17175626
TI  - Performance of emergency medicine residents on a novel practice examination using
      visual stimuli.
AB  - OBJECTIVES: In 2004, the format of the Royal College of Physicians and Surgeons
      of Canada certification exam in Emergency Medicine was modified to include an
      audiovisual session. Residents' performance on such stimuli is unknown. This
      study aims to determine the performance of Emergency Medicine postgraduate year 5
      (PGY-5) on a novel practice examination using visual stimuli, in an effort to
      guide residents' preparatory study, and to help educators focus the teaching
      related to visual stimuli. METHODS: In this prospective observational study, 30
      PGY-5 residents from 12 Emergency Medicine programs across Canada participated in
      a practice examination in which they had to answer 133 questions related to 80
      visual stimuli. The stimuli included electrocardiograms, medical imaging and
      clinical photographs. Three experienced faculty provided "reference standard"
      answers for the visual stimuli. For analysis purpose, stimuli were classified
      into 9 clinical domains, outlined in The Model of the Clinical Practice of
      Emergency Medicine. RESULTS: Insufficient question numbers in 3 domains prevented
      reliable inferences. Correct answers were given for 65% of remaining questions,
      with the following domain distribution: 69% respiratory, 64% trauma, 73%
      cardiovascular, 62% head-eyes-ears-nose-throat (HEENT), 63% musculoskeletal and
      69% cutaneous. Seventy-four percent of ECGs, 64% of imaging, and 62% of
      photograph-related questions were answered correctly. Incorrect answers were
      related to a lack of knowledge as well as imprecise or incomplete responses.
      CONCLUSIONS: PGY-5 subjects scored lowest in the HEENT and musculoskeletal
      domains. Medical educators should emphasize these domains in their teaching, and
      insist on precision and completeness of answers.

PMID- 17175627
TI  - Potential value for new diagnostic markers in the early recognition of acute
      coronary syndromes.
AB  - The diagnostic approach to acute coronary syndromes (ACS) remains one of the most
      difficult and controversial challenges facing emergency physicians. In recent
      years, cardiac troponins have emerged as the biochemical "gold standard" for
      diagnosis of patients with acute chest pain, enhancing our ability to recognize
      ACS. Early diagnosis and treatment of myocardial ischemia improve patient
      outcomes, but conventional markers are often nondiagnostic at the time of arrival
      at the emergency department. Promising new biomarkers, which appear earlier after
      the onset of ischemia, are being studied and integrated into clinical practice.
      Some are markers of myocyte necrosis, but others, including ischemia-modified
      albumin and natriuretic peptides, detect myocardial ischemia and myocardial
      dysfunction. The aim of the present article is to review the diagnostic approach
      to ACS, focusing on recent literature describing novel biochemical markers. If
      ongoing and future studies confirm their role in probability-based models risk
      assessment, a new era in the diagnostic approach to ACS may be dawning.

PMID- 17175628
TI  - Clinical utility of novel cardiac markers: let the buyer beware.

PMID- 17175629
TI  - 2005 emergency cardiovascular care guidelines.

PMID- 17175630
TI  - Should hyperbaric oxygen be used for carbon monoxide poisoning?

PMID- 17175631
TI  - Should emergency physicians be using a more extensive form of ultrasound to
      assess non-traumatic hypotensive patients?

PMID- 17175632
TI  - Atlanto-occipital dislocation: case report and discussion.
AB  - Atlanto-occipital dislocation (AOD) is a devastating condition that frequently
      results in prehospital cardiorespiratory arrest and accounts for 15% of fatal
      spinal trauma. Atlanto-occipital dislocation occurs 5 times more commonly in
      children than adults, and is believed to be caused by hyperextension. Because of
      improvements in prehospital resuscitation, more victims with AOD now survive to
      reach the emergency department. Neurologic injury is usually severe secondary to
      ligamentous disruption that allows the cranium to move with respect to the
      cervical spine, and associated facial and head injuries are common. There are,
      however, reports of survivors without neurologic deficits. We present the case of
      a 46-year-old woman who suffered an AOD after a motor vehicle crash and we
      discuss the diagnosis of this condition. The signs of AOD are often subtle, and
      the possibility of this diagnosis must be kept in mind in all patients with a
      neck injury, even in the absence of neurologic signs. A systematic approach to
      assessing the cranio-cervical relationship on the lateral cervical x-ray and the
      appropriate use of CT scanning is essential to identifying AOD. Through this case
      report we hope to familiarize clinicians with mechanisms of injury and
      appropriate imaging interpretation that will assist in the diagnosis of AOD.

PMID- 17175633
TI  - Turning a stroke into a TIA: curative thrombolysis with combined intravenous and
      intra-arterial tPA.
AB  - Intravenous tissue plasminogen activator (tPA) is standard treatment for eligible
      patients with acute ischemic stroke, but may be less effective for very severe
      strokes caused by proximal intracranial artery occlusions. We report the case of
      a woman with a devastating stroke who recovered completely following emergency
      revascularization of an occluded proximal middle cerebral artery using a novel
      treatment approach that combines both intravenous (i.v.) and intra-arterial (IA)
      tPA. This case illustrates the potential value of the combined i.v.-IA
      thrombolytic approach, which is an emerging investigational treatment strategy
      for selected patients with severe acute ischemic stroke.

PMID- 17175634
TI  - [Cross-talk between iNOS and COX-2 pathways in inflammatory response and anti
      inflammatory effect of insulin].

PMID- 17175635
TI  - [Analysis of the influence on the prognosis and safety of arginine in patients
      with severe trauma and burns--a multi-center randomized double blinded, placebo
      controlled, clinical trail in 86 patients].
AB  - OBJECTIVE: To observe the influence on prognosis and possible side-effects of
      arginine in METHODS: Multi-center clinical trial, randomized double blinded
      patients with severe trauma and burns. and placebo control methods were employed
      in the study. Eighty-six patients with severe trauma and burns were randomly
      divided into control (C, n = 45) and arginine treatment (Arg, n = 41) groups. The
      patients in Arg group received arginine in dose of 0. 4 g x kg(-1) x d(-1)
      orally, while those in C group received same dose of placebo (tyrosine) for 7
      days. All the patients in both groups were given diet with equal calories and
      equal nitrogen content. The changes in the wound healing time, hospital stay, and
      the incidence of side-effects of the medication in both groups of patients were
      observed and compared before and after the supplementation of arginine. RESULTS:
      The wound healing time and hospital stay days of severe trauma patient in Arg
      group (n = 29) were 11. 1+/-2. 8 d and 19+/-6 d, which were all obviously shorter
      than those in C group (13. 2+/-5. 5 d, 22 +/-6 d, n =33, P <0.05). On the other
      hand, in severe burn patients there were no significant difference of the wound
      healing time (20+/-5 d vs 22+/-8 d, n = 12, P > 0. 05) and hospital stay days
      (28+/-6 d vs 29+/-8 d, n = 12, P >0. 05) between the Arg and C groups. In
      addition, in C and Arg groups, the occurrence of the side-effects were seldom (2.
      44% vs 2. 22% , P = 1. 000) and it disappeared when the supplementation of drugs
      was stopped. CONCLUSION: Oral feeding of arginine is beneficial in enhancing
      wound healing, reduction of hospital stay days in severe trauma patients and with
      little side-effects, but it is not beneficial to improve the prognosis of severe
      burn patients. Maybe this is due to inadequate number of case involved in the
      study.

PMID- 17175636
TI  - [Influence of intravenous infusion of D-fructose on post-operative blood glucose
      level in burn patients].
AB  - OBJECTIVE: To investigate the influence of intravenous infusion of 50 g/L
      fructose on post-operative blood glucose level in burn patients, and to evaluate
      its therapeutic value and safety. METHODS: A prospective, randomized, double
      blinded clinical trial was conducted. Forty-one burn patients with burn area
      ranging between 10% -30% of total body surface (TBSA) and third degree burns
      ranging between 1% -10% TBSA were enrolled in the study and randomized into
      experiment group (E, n = 21, with intravenous infusion of 500 ml of 50 g/L
      fructose daily for 3 days after escharectomy) and control group ( C, n = 20, with
      intravenous infusion of glucose 1 day after escharectomy for 3 days). Intravenous
      infusion of other carbohydrate liquids or oral intake of sugar was withhold
      within 4 hours of fructose or glucose infusion. Physical signs and side effects
      were observed during the administration. The plasma glucose contents before
      operation and on 1, 2 and 3 post-operation day( POD) were measured. The serum
      content of lactic acid, uric acid, hepatic and renal function were determined
      before operation and on 4 POD. RESULTS: Physical signs before and after drug
      administration, and plasma glucose content before operation, as well as before
      and after fructose administration in 3 POD exhibited no obvious difference
      between the two groups ( P > 0. 05 ). The plasma glucose content was increased 3
      days after operation in the control group, and it reached the peak on 3 POD [ (8.
      4+/-3. 5) mmol/L] , which was markedly higher than that before glucose
      administration [ (6. 4+/-2.4) mmol/L, P <0. 01) ]. The plasma contents of lactic
      acid and uric acid showed no obvious difference ( P >0.05) between the two
      groups, and also no difference before and after operation ( P > 0. 05). No
      changes were observed in hepatic and renal functions. CONCLUSION: Intravenous
      infusion of 50 g/L D-fructose is safe because it exerts little influence on blood
      glucose level.

PMID- 17175637
TI  - [Changes in the expression of rat hepatic lipid metabolism related genes in
      response to burn wound sepsis as assessed by DNA arrays].
AB  - OBJECTIVE: To examine the expression profile of lipid metabolism-related genes in
      liver of scalded rats with wound sepsis, and to analyze its significance.
      METHODS: Sixty male Wistar rats with 30% TBSA full-thickness scald wound on the
      back were enrolled in the study and randomly divided into wound sepsis group (n =
      30) and control group (n = 30, with scald). Pseudomonas aeruginosa was inoculated
      to the wounds in sepsis group. Corresponding indices were determined to verify
      the diagnosis of wound sepsis. The rats were sacrificed and fresh liver tissues
      were obtained at 96 post-scald hours (PSH). Total RNA of liver was isolated with
      Trizol and the different expression of lipid metabolism related genes in response
      to burn wound sepsis was assessed by DNA microarray. RESULTS: By comparing
      expression profile of the two groups, totally 47 genes were observed to be
      differentially expressed in rat hepatic tissues, among them 9 genes were related
      to lipid metabolism. Among them, those which were upregulated were genes in
      relation with transportation and activation of fatty acid, and those
      downregulated were genes related in providing energy for fatty acid oxidation in
      mitochondria. CONCLUSION: The occurrence of wound sepsis in scalded rats can
      induce changes in the expression of hepatic lipid metabolism related genes in
      hepatic tissues, and aggravate

PMID- 17175638
TI  - [The influence of apoptosis of lymphocytes of Peyer's patches on the pathogenesis
      of gut barrier damage in severely scalded mice].
AB  - OBJECTIVE: To investigate the changes in cellular apoptosis of Peyer's patches in
      severely scalded mice, and to explore its role in the pathogenesis of gut barrier
      damage. METHODS: Forty BALB/c mice were randomly divided into normal control, 12
      post-scald hour (12PSH), 24PSH and 72PSH groups, with 10 in each group. The mice
      in all PSH groups were inflicted with 20% TBSA full-thickness scald on the back.
      The mice in all the groups were sacrificed at different time points, and Peyer's
      patches were harvested from all the mice for HE staining, DNA gel
      electrophoresis, and flow cytometry ( FCM) examination with FITC conjugated
      Annexin-v and propidium iodide( PI) staining of cells. RESULTS: HE staining
      revealed that there were relatively abundant apoptotic cells scattering in
      Peyer's patches of scalded mice . DNA electrophoresis of Peyer's patches revealed
      typical " ladder" pattern at all indicated time points in scalded mice. Apoptotic
      percentage of detached Peyer's patches cells in control and scalded group were
      (4. 9+/-2. 1)% , (26.7+/-3. 1)% , (21.6 +/-4.0)% ,(12. 8 +/-2.0)% , respectively,
      and the percentage reached the peak at 12 PSH. CONCLUSION: Apoptosis is a
      principle modality of cell death of small intestinal Peyer's patches lymphocytes
      in severely scalded mice, and it might contribute to immunity barrier failure of
      intestinal wall after severe thermal injury.

PMID- 17175639
TI  - [Transfection and identification of the cloned strain that stably expressing
      glucagon like peptide-2 receptor in CaCO2 cell lines].
AB  - OBJECTIVE: To establish Caco2 cell line with stable expression of glucagon like
      peptide-2 receptor( GLP-2R) , in order to establish an in vitro model for the
      study of protective mechanism of GLP-2 of the intestinal tract. METHODS: The GLP
      2R/pcDNA3. 1 ( + ) plasmid was verified by restriction endonuclease and
      sequencing , and then it was transfected into Caco2 cells with lipofectamine.
      After G418 selection, the clones with stable expression of GLP-2R were obtained
      by limited dilution cloning and expanding. The mRNA and protein expression of GLP
      2R in normal human intestine, Caco2 cells, HER293, VE cells, as well as in
      transfected Caco2 cells were determined with RT-PCR and Western blot. RESULTS:
      The sequence of GLP-2R/pcDNA 3. 1 plasmid was correct. No expression of GLP-2R
      mRNA and protein was found in HER293 and VE cells, but weak expression were found
      in Caco2 cells, and strong expression was found in normal human intestines. The
      expression of GLP-2R mRNA and protein expression in Caco2/GLP-2R ( + ) cells were
      obviously increased after transfection. CONCLUSION: GLP-2R has special
      distribution. The expression of GLP-2R is weak in normal Caco2 cells. The
      establishment of Caco2/GLP-2R ( + ) cellular model is beneficial for the further
      research of the mechanism of action of GLP-2.

PMID- 17175640
TI  - [Effects of insulin on proteolysis of cultured rabbit skeletal muscular myotubes
      in vitro].
AB  - OBJECTIVE: To study the effects of insulin on the proteolysis of cultured rabbit
      skeletal muscular myotubes in vitro, and their possible mechanisms. METHODS:
      Muscles of lower limbs of juvenile rabbits were isolated for tissue-block
      culture. After passage, myoblasts were formed and fused into myotubes. Then the
      protein in myotubes was radiolabelled with L-[ 3,5-3H] tyrosine. The myotubes
      were cultured in DMEM medium containing 100 nmol/L insulin (n = 24, group B) ,
      100 nmol/L dexamethasone (n = 24, group C) , 100 nmol/L insulin and 100 nmol/L
      dexamethasone (n = 24, group D) , no insulin or dexamethasone (n =24, group A),
      respectively. Twenty-four hours after culture, the L-[3,5-3H] tyrosine content in
      culture medium and cells were determined, and the degradation rates of protein
      were calculated. The mRNA expressions of ubiquitin and protease C2 subunit were
      determined by Northern blot. RESULTS: The degradation rates of myotube protein in
      group A(0. 38+/-0.04) was obviously lower than that in group C (0.50+/-0.03, P
      <0.01), but it was obviously higher than that in group B(0. 35+/-0.03, P <0.05).
      Though the degradation rates of myotube protein in group D (0.41+/-0. 03) was
      evidently lower than that in group C ( P < 0.01) , it was still higher than that
      in group A( P < 0.05 ). The mRNA expressions of ubiquitin and protease C2 subunit
      in group A ( the scale: 2. 4 kb ubiquitin was 0. 82+/-0. 15, 1. 2 kb ubiquitin
      was 0. 60+/-0. 10, C2 subunit was 0. 75+/-0. 16) was obviously lower than that in
      group C ( the scale: 2.4 kb ubiquitin was 2. 15+/-0. 23, 1.2 kb ubiquitin was
      1.50+/-0. 14,C2 subunit was 1.50+/-0. 13 , P <0. 01) , but it in group D was
      lower than that in group C (the scale: 2. 4 kb ubiquitin was 1. 25+/-0. 17, 1. 2
      kb ubiquitin was 0. 85+/-0. 09, C2 subunit was 0. 90+/-0. 15, P <0. 01) , and it
      was similar to that in group B (the scale: 2.4 kb ubiquitin was 0. 85+/-0.07, 1.2
      kb ubiquitin was 0. 65+/- 0. 12, C2 subunit was 0. 76 +/-0. 09, P > 0. 05).
      CONCLUSION: The effects of insulin on the activity of ubiquitin-proteasome
      pathway and the proteolytic rate in normal myotubes were relatively weak.
      However, insulin can significantly inhibit the effects of dexamethasone on the
      gene expressions of ubiquitin system and the proteolytic rate in myotubes, but
      the mechanism needs further research.

PMID- 17175641
TI  - [Clinical observation on the paraumbilical skin flaps application in the repair
      of the wounds of 39 patients with severe burns].
AB  - OBJECTIVE: To evaluate the effectiveness of paraumbilical skin flaps for the
      repair of the severe burn wounds. METHODS: Pedicled, island, or free
      paraumbilical skin flaps, as well as combined transplantation of several kinds of
      flaps were used to repair the wounds of 39 patients with severe burns. The
      largest paraumbilical skin flap was 55 x 27 cm(2) in area, with the end
      approaching the armpit midline of the axilla on the same side, and extending 10cm
      from the abdominal midline. The survival, color, elasticity of the flaps, degree
      of deformity resulted from scar contracture, and the condition of donor area were
      observed. RESULTS: All the paraumbilical skin flaps survived, without obvious
      infection subsequent to complete debridement of the wounds. The flaps exhibited
      good color and elasticity, without scar contracture after 1 to 46 months in 33
      patients. No obvious scar formation was observed in the donor area. CONCLUSION:
      Paraumbilical skin flap is an ideal one for the early repair of deep burn wounds,
      because it can cover a large area, and can be transferred in different ways
      according to the area and the position of the wounds.

PMID- 17175642
TI  - [Effects of citrus reticulata blanco extract on fibroblasts from human
      hypertrophic scar in vitro].
AB  - OBJECTIVE: To investigate the effects of citrus reticulata blanco extract on the
      proliferation and collagen metabolism of fibroblasts from human hypertrophic
      scar. METHODS: Human hypertrophic scar fibroblasts from two burn patients
      obtained from plastic surgery were cultured in vitro and divided into
      experimental group (n = 12, with basic culture medium and 2.5, 5.0, 10.0,25.0
      mg/L citrus reticulata blanco extract, respectively, 3 bottles for each
      concentration of citrus reticulata blanco extract ), control group 1 (n = 3, with
      basic culture medium) , and control group 2 ( n = 3, with basic culture medium
      and 5% ethyl alcohol). The cell proliferation in each group was observed with MTT
      method, then the inhibition rate was calculated. Apoptosis and its index ( AI) in
      each group were determined after TUNEL staining . The changes in the content of
      ICTP and PINP in each group were observed by radioimmunity. RESULTS: The
      inhibition rate in the experimental group with the citrus reticulata blanco
      extract in concentration of 2. 5, 5.0, 10.0, 25. 0 microg/ ml were (7. 100+/
      0.038)% , (8. 100+/- 0. 048)% , (10. 900+/-0. 055)%, (15.900+/-0. 097) %,
      respectively, which were significantly higher than those in other two groups ( P
      <0.05 ). The Al (69. 7% , 71.7%, 86.4% , 95.2% ), ICTP [(17.2+/-0.6), (18.3+/
      0.6), (19.8+/-0.5), (23.2+/-0.6) microg/L] and PINP [ (101.7+/-1.4) , (107. 8+/
      1. 1) , (111.6+/-1.2) , (124. 6+/-1.3) microg/L] in experimental group with the
      citrus reticulata blanco extract in concentration of 2.5, 5.0, 10.0 , 25.0 mg/L
      were also obviously higher than other two control groups( P <0.05) ,but these
      indices in control 1 group were similar to those in control 2 group( P >0. 05).
      CONCLUSION: The citrus reticulata blanco extract might be beneficial for the
      management of hypertrophic scar through inhibition of the proliferation of
      fibroblasts in hypertrophic scar, by promoting apoptosis and collagen
      degradation.

PMID- 17175643
TI  - [Influence of scald on the cytoskeleton of colonic smooth muscle cells of the
      rats].
AB  - OBJECTIVE: To investigate the changes in the morphology and cytoskeleton (CSL)
      content of the CSL in the colonic smooth muscle cells (SMCs) of rats in early
      postscald stage, so as to elucidate the mechanism of dysfunction of
      gastrointestinal motility. METHODS: Seventy Wistar rats were randomly divided
      into normal control (n = 10, without scald) , and scald ( n = 60, with 10 cm x 7
      cm wound inflicted on the back) groups. The colonic smooth muscle tissue of 10
      normal rats and scalded rats were harvested at 1, 3, 6, 12, 24 and 48 postscald
      hours( PSH) and divided into two parts: one for histologic examination, and the
      other for the detection of CSL changes in the colonic smooth muscle tissue by
      flowcytometry method. RESULTS: The electron microscope examination showed that
      the arrangement of cytoskeleton of SMC of the scalded rats during 1 to 3 PSH was
      disordered, and sparse, and the condensed area was uneven, with fragmentation.
      But the morphology and distribution of CSL gradually restored to normal state
      during 6 to 12 PSH, and it approached that of normal group at 48 PSH. The CSL
      content in the colonic smooth muscle tissue of scalded rats was obviously
      increased at 1 PSH (610+/-23) , decreased thereafter, evidently lower than that
      in control group at 3 PSH (92+/-17) , and then it started to increase at 12 PSH,
      exceeding the normal value at 24 PSH, and continued to rise until 48 PSH. There
      was significant difference in CSL content in the colonic smooth muscle tissue of
      the rats between scald and control group ( P < 0.05 or 0. 01). CONCLUSION:
      Changes in the morphology and CSL content in the colonic smooth muscle tissue can
      be observed at early stage after a scald, which imply the kinetic balance between
      damage and repair in the body. In addition, changes in CSL content in the colonic
      smooth muscle tissue may be important factors in producing colonic dysfunction,
      damage of intestinal wall structure, and dynamic abnormalities of the colonic
      smooth muscle.

PMID- 17175645
TI  - [Clinical research of the effect of shengmai injection on the management of
      "shock heart " after burns].
AB  - OBJECTIVE: To investigate the effect of Shengmai injection on the management of
      "shock heart" after burns. METHODS: Twenty patients with severe burns were
      enrolled in the study and randomly divided into two groups according to the
      clinical research method, i.e. treatment group (n= 10, with intravenous infusion
      of 40 ml Shengmai injection together with 250ml 50 g/L glucose solution for 3
      days, 1 time/ per day) and control group(n = 10, with intravenous infusion of 290
      ml 50 g/L glucose injection liquid for 3 days, 1 time/per day). Beside the venous
      line used for routine fluid resuscitation for burn shock, another venous line was
      set up after hospitalization for the administration of the drug. Blood samples
      were obtained from the femoral vein in both groups at 12 post-burn hour( PBH) ,
      and on 1, 2, 3, 4 and 5 post burn days (PBD) for the determination of serum
      contents of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and cardiac
      troponin I (cTnI). The changes in hepatic and renal function, as well as
      coagulability were determined before drug infusion and on 1 , 2, 3, 5 and 7 PSDs.
      RESULTS: The serum content of CK-MB, LDH and cTnI reached the peak at 12 PBH in
      both groups[ (52+/-20)U/L, (5.9+/-1.3) micromol x s(-1) L(-1), (0. 274+/-0. 231)
      microg/L in treatment group and [(9+/-31)U/L, (8.5+/-1l.8) micromol x s(-1) x L(
      1) , (0. 584+/-0. 192) microg/L in control group]. All of them decreased with the
      passage of time, but in the treatment group they decreased more markedly within 2
      or 3 PBD compared with those in control group ( P < 0.05). CONCLUSION: Early
      administration of Shengmai intravenously is beneficial to the protection of
      myocardial cells and in the management of the "shock heart" damage.

PMID- 17175644
TI  - [Influence of substance P on the proliferation and apoptosis of fibroblasts of
      pathological scars].
AB  - OBJECTIVE: To further explore the effects of substance P on the proliferation and
      apoptosis of fibroblasts obtained from pathological scars in vitro. METHODS:
      Fibroblasts from keloid (KSF) , hypertrophic scar (HSF) and normal dermis (NDF)
      of 12 burn patients were cultured in vitro and divided into control, SP (with 1 x
      10 (-6) mol/L SP added to the culture medium) , and SP + spantide( with 1 x 10 (
      6) mol/L SP and 3 x 10 (-5) mol/L spantide added to the culture medium) groups.
      MTT method or flow cytometry assay was used for the determination of the
      proliferative activities or apoptotic rate of fibroblasts obtained from KSF, HSF
      and NDF with SP or Spantide. And then the fibroblasts in SP group were subdivided
      into 1 x 10( -9) -1 x 10 (-5) mol/L groups to examine the time-or dose-effect of
      SP to fibroblasts from different sources. RESULTS: In control group, different
      types of fibroblasts exhibited similar proliferative activities and apoptotic
      rates. But there was significant difference in these indices between control and
      SP group (the proliferative activity of KSF, HSF, NDF was 0. 656+/-0. 071, 0. 525
      +/-0. 064, 0. 404+/-0. 063, respectively; and the apoptotic rate of KSF, HSF, NDF
      was [( 1.5+/-0.3) % , (4.0+/-0.5) % , (5.5+/-0.7) % , respectively],( P < 0. 05).
      SP had stronger effect on KSF than it did to HSF, as well as it had stronger
      effect on HSF than it did to NDF. In SP + spantide group, the effect of SP on KSF
      was partially inhibited, while it was completely inhibited in cultures of HSF and
      NDF. KSF was more sensitive to SP and the effect was longer when compared with
      HSF. CONCLUSION: SP may play an important role in the process of pathological
      scar formation due to its diverse effects on fibroblasts from different sources.

PMID- 17175646
TI  - [Analysis and evaluation of the articles concerning animal experiments published
      in Chinese Journal of Burns during 2000 to 2004].
AB  - OBJECTIVE: To investigate the current situation of animal experiments by analysis
      and evaluation of relevant articles published in the Chinese Journal of Burns
      during 2000 to 2004. METHODS: All articles concerning the results of animal
      experiments related to the treatment and medical studies in the past 5 years were
      analysed according to the international standard , especially in serval aspects,
      such as sample size, randomization method, sample choice, comparison measure,
      baseline comparability, estimate index, statistics method, and so oN. RESULTS:
      During 2000 to 2004, totally 1 116 papers were published in the journal, among
      them 81 papers were (accounted for 7.3% ) of all articles were reports of
      treatment related experiments. Out of 81 papers, in 69 experiments ( accounted
      for 85. 2% ) there was randomized control group, and the main problems lay in
      calculation of the number of samples, the application of randomization method,
      and analysis of statistics. CONCLUSION: Application of the randomized control
      modality in animal experiment is popular in our country, but the design of some
      studies is not so rigorous. Therefore, we should improve the design of every
      research project before the experiment is carried out.

PMID- 17175647
TI  - [Investigation and analysis of the self-esteem level and social adaptation
      ability of hospitalized burn patients].
AB  - OBJECTIVE: To investigate the self-esteem level and social adaptation ability of
      hospitalized burn patients in our burn ward. METHODS: One hundred and twenty
      hospitalized burn patients in our burn ward were enrolled in the study and
      evaluated according to their sex, severity of burn injury and education level.
      Their self-esteem level and social adaptation ability were scored with the
      Felling of Inadequacy Scale and Abbreviated Burn Specific Health Scale. RESULTS:
      The general score of self-esteem of the patients with mild burns( 183+/-23) was
      obviously lower than that with moderate and severe burns (167+/-21 and 154 +/-24)
      , ( P <0.01). The self-esteem level of burn patients was different in different
      sex and education level. Among the self-esteem scores, male burn patients
      presented evidently higher scores of self evaluation, social ability, appearance,
      as well as the general score than those in the female ( P < 0.05). Moreover, the
      self evaluation score and study ability was higher in those with higher education
      level than those with lower education. Furthermore, the score of social
      adaptation ability was higher in the patients with mild burns than that in
      patients with moderate and severe burns ( P < 0. 01). The social adaptation
      ability and psychological function were much higher in male patients than those
      in female patients, but the former were weaker than the latter in regard to the
      body function. The psychological function, social relationship and general
      condition of the patients with lower education were better than those with higher
      education ( P <0. 05 ). CONCLUSION: There existed difference in the self-esteem
      and social adaptation ability in different burn patients during different
      periods.

PMID- 17175648
TI  - [Study on the expression, purification and the anti-endotoxin activity of human
      endotoxin binding peptide and its mutant].
AB  - OBJECTIVE: To express endotoxin binding peptide and its mutant in E coli DH5alpha
      and detect the antiendotoxin activity of the purified peptides. METHODS: (1 ) E
      coli DH5at containing pinpointXa3-EBP and pinpointXa3-mEBP was activated by IPTG
      to express biotin fusion protein. The fusion proteins were purified, and then
      digested by factor Xa for isolation of EBP and mEBP. The target peptide was
      purified with affinity chromatography and reversed-phase HPLC. Sequences of 10
      amino acids at N-terminal were used for identification of mEBP. (2) PBMCs were
      isolated from blood of normal people, and they were stimulated with 5 mg/L FITC
      LPS plus 2.0,5. 0 and 12. 5 mg/L EBP or mEBP. Then the mean fluorescent intensity
      was detected. PBMC was also stimulated with 1 mg/L LPS plus 2.0, 5.0 and 12.5
      mg/L EBP or mEBP for 5 hours for the detection of the TNF-alpha and IL-6 level in
      the supernatant. (3) Thirty-five Kunming mice were randomized into normal control
      ( n = 5, with intraperitoneal injection of 0. 2 ml isotonic saline) , model
      group(n = 5, with intraperitoneal injection of LPS and 20% TBSA full-thickness
      burns), and treatment group (n = 15, with intraperitoneal injection of 5 mg/kg
      PMB or 10 mg/kg EBP or mEBP after burns). The serum contents of TNF-a and IL-6,
      and TNF-alpha mRNA level in hepatic tissue in each group were determined 6 hours
      after treatment. RESULTS: ( 1 ) EBP and mEBP were obtained after Xa digestion of
      biotin fusion protein, with purity reaching above 98% . The sequence of 10 amino
      acid at N-terminal was in accord with what expected. (2) The fluorescent
      intensity was decreased followed by an increase in mEBP or EBP concentration.
      Compared with normal PMBC, IL-6 and TNF-alpha level in the supernatant were
      obviously lowered in 1 mg/L LPS + 12.5 mg/L EBP group and I mg/L LPS +2. O0 , 5.
      0, 12. 5 mg/L mEBP groups ( P < 0.01). (3) The serum level of IL-6 and TNF-ca in
      the therapeutic groups were obviously lower than that in model group ( P < 0.01 )
      , and the levels of these cytokines were significantly lower in 10 mg/kg mEBP
      group than that in 10 mg/kg EBP group ( P <0. 01) , but they were similar to that
      in 5 mg/kg PMB treatment group ( P >0.05). (4) Relative optical density of TNF
      alpha. mRNA in control, model, 10 mg/kg mEBP, 10 mg/kg EBP and 5 mg/kg PMB groups
      was 0.25, 0.93, 0.51 , 0.77 and 0.43, respectively. CONCLUSION: Endotoxin binding
      peptides can be obtained by procaryon expression. Both EBP and mEBP have anti-LPS
      activity, but mEBP is more effective.

PMID- 17175649
TI  - [Experimental study on xenogenic acellular dermal matrix incorporated with
      silver].
AB  - OBJECTIVE: To investigate the biological characteristics of xenogenic acellular
      dermal matrix( Xeno-ADM) incorporated with silver, and to observe its effect in
      grafting. METHODS: Xeno-ADM was prepared with 0. 25% trypsin and 0. 5% triton X
      100 , and then it was immersed in 2 g/L silver nitrate solution to prepare xeno
      ADM incorporated with silver. The bacterial inhibitory effect of two kinds of
      xeno-ADM on burn wound was determined, and the histological characteristic of the
      wounds was observed with optical microscope, transmission electron microscope and
      scanning electron microscope. The Ag+ content in the xeno-ADM incorporated with
      silver was measured with atomic absorption spectrometer. Twenty-seven rabbits
      with full-thickness skin defects on the back were randomly divided into three
      groups, i. e. split-thickness skin autograft only( group A, n = 9) , xeno-ADM
      with overlying split-thickness skin autograft( group B, n = 9) , xeno-ADM
      incorporated with silver with overlying split-thickness skin autograft ( group C,
      n = 9). The skin specimens from grafted area in each group were harvested at 2,4
      and 6 post-operation weeks( POW) and examined under light microscope and
      transmission electron microscope. The condition of the graft, the contraction
      degree of the grafts and the historical changes in grafting area were observed at
      2,4,6 POW. The survival rate of the grafts was calculated and the proliferative
      activity of the lymphocyte in each group was determined at 2 POW. RESULTS: 1.
      Compared with xeno-ADM, the anti-bacterial effect of xeno-ADM incorporated with
      silver was much better ( P < 0. 05). No epidermis was seen in both types of
      xenografts ,and the collagen fibers were even in size and arranged regularly,
      with no obvious degeneration, and the dermis was also devoid of cells and
      cellular components. The Ag + content in xeno-ADM incorporated with silver
      measured (2. 7+/-0. 7) mg/g. 2. The grafts in B and C groups presented similar
      color to that of normal skin at 6 POW, and it was smooth, with fine texture and
      no scarring. The collagen fibers was arranged regularly, and conjunction between
      epidermis and dermis, the structure of basal cell desmosome and semi-desmosome
      were well reconstructed. The grafts in A group was in dark red color, with
      obvious contraction, and easily broken. The contraction rate in A group at 2,4
      and 6 POW were obviously higher than those in B and C groups( P < 0. 05), while
      no obvious difference was observed between B and C groups. ( P >0. 05). The
      overall survival rate of the grafts in C group at 2 POW was 91.7% , which was
      evidently higher than that in A (77.8%) and B (80. 6% ) groups. The lymphocyte
      proliferative activity exhibited no difference among A, B and C groups( P >0.05).
      CONCLUSION: The xeno-ADM incorporated with silver has good anti-bacterial effect.
      In addition, it preserves the basic tissue structure and integral collagen fiber
      scaffold, without cells to induce rejection, so that it can be used as an ideal
      dermal substitute.

PMID- 17175650
TI  - [Changes in the calcitonin content after inhalation injury in dogs].
AB  - OBJECTIVE: To investigate the changes in the serum content of immunoreactive
      calcitonin (iCT) after burns or inhalation injury, and to explore its diagnostic
      significance. METHODS: Twenty-four dogs were randomized into 4 groups, i. e. A (n
      = 6, with moderate degree inhalation injury) , B ( n = 6, with severe inhalation
      injury), C (n = 6, with most severe inhalation injury) and D (n = 6, with severe
      burns) groups. The serum content of iCT and blood gas analysis before and after
      injury were determined at different time points. The degree of inhalation injury
      was determined with fibrobronchoscopic examination at 6 post-inhalation injury
      hour (PIH). RESULTS: (1) Fiber bronchoscopic examination showed that the degree
      of inhalation injury in each group was coincident with the anticipation. (2) The
      serum content of iCT in each group at 1 PIH was obviously higher than that before
      injury, and it was evidently higher in A, B and C groups than that in D group at
      4 PIH. The peak value of iCT in group A at 24 PIH was (453+/-224) ng/L, and it
      increased gradually in B and C groups at 48 PIH. The serum content of iCT
      increased continually from 2 PIH on, and it reached (125+/-41) ng/L at 48 PIH.
      (3) Compared with PaO2 value before injury (109+/-8) mmHg, there was no obvious
      difference of the PaO, in A and D groups. PaO2 value in B and C group began to
      descend continually at 8 PIH (65+/-6) mmHg, and that in C group began to descend
      at 4 PIH (71+/-9) mmHg. PaCO2 value in C group began to increase at 24 PIH(52+/
      11) mmHg when compared with that before injury(38+/-5 ) mmHg. CONCLUSION: The
      changes in the serum level of iCT within 8 PIH occurred much earlier than PaO2
      and PaCO2, thus it has the same diagnostic significance as fibers bronchoscopic
      examination.

PMID- 17175651
TI  - The relative effect of self-management practices on glycaemic control in type 2
      diabetic patients in Mexico.
AB  - OBJECTIVE: In this study, we examined the relative impact of self-management
      activities on glycaemic control in a population at high risk for developing
      complications. METHODS: Patients diagnosed with diabetes mellitus of at least 1
      year in duration at 30 years of age or older were sampled from the Instituto de
      Mexico Seguro Social (IMSS) Family Medicine Clinics in Guadalajara, Mexico
      (n=800). Demographic, clinical and health behaviour variables were used to
      predict good/poor glycaemic control, as measured by haemoglobin Alc (A1C).
      RESULTS: Most (72.24%) patients had poor control (A1C > or = 7.0). Hyperglycaemia
      was significantly associated with factors not under patient control, such as
      having diabetes for a longer time [odds ratio (OR) = 2.40, 95% confidence
      interval (CI) 1.39, 4.14], having a first-degree relative with diabetes (OR=
      1.52; 95% CI 1.06, 2.19), and being prescribed anti-diabetic medications, e.g.
      insulin (OR = 7.88, 95% CI 2.42, 25.63). After controlling for these variables,
      the only self-management variable that reduced the likelihood of hyperglycaemia
      was following a special diet (OR=0.49; 95% CI 0.32, 0.76). Furthermore,
      depression had an important effect on self-management, as those with lower levels
      of depressive symptoms were more likely to follow a diet and exercise.
      DISCUSSION: While patients in this population have little control over many
      factors associated with glycaemic control, an important exception is diet.
      However, because of the adverse effect of depression on dieting, both depression
      management and dietary education are important for this population.

PMID- 17175652
TI  - Use of telephone care in a cardiovascular disease management programme for type 2
      diabetes patients in Santiago, Chile.
AB  - OBJECTIVES: In 2004, the Chilean National Ministry of Health instituted a
      cardiovascular disease (CVD) management programme aimed at improving diabetes
      care among patients treated in the public healthcare system. We sought to
      identify the characteristics of patients participating in the CVD programme and
      the feasibility of extending its reach through structured nurse telephone
      contacts between outpatient encounters. METHODS: We surveyed 569 low-income
      adults with type 2 diabetes treated in public clinics of Santiago, to assess
      patients' participation in the CVD programme and willingness to use telephone
      care services. Surveys were linked to information from medical records. RESULTS:
      One-third of patients met the target of two visits to the CVD programme in the
      previous 6 months, and an additional 32% made more than three visits. Use of the
      CVD programme was associated with greater patient satisfaction, even after
      controlling for potential confounders. However, 27% of patients had inadequate
      programme contact, and many of these patients were in poor health. Many CVD
      programme participants reported difficulties with lifestyle changes, and greater
      contact with the CVD programme was not associated with healthier behaviours. Most
      patients (95%) reported telephone access and 37% had used the telephone to
      contact their clinic. The majority of patients would be willing to use telephone
      care for additional behaviour change and emotional support. Patients with fewer
      CVD programme visits were particularly likely to report willingness to use
      telephone care. DISCUSSION: Clinic-based CVD disease management services reach a
      large number of socio-economically vulnerable Chileans with diabetes. However,
      barriers to access remain, and planned telephone care services may increase the
      reach of self-management support.

PMID- 17175653
TI  - Cost-effectiveness analyses and modelling the lifetime costs and benefits of
      health-behaviour interventions.
AB  - BACKGROUND: We describe an approach to estimating the cost-effectiveness of an
      intervention that changes health behaviour. The method captures the lifetime
      costs and benefits incurred by participants in an ongoing cluster-randomized
      controlled trial of an intervention that aims to change health behaviour. The
      existing literature only captures short-term economic and health outcomes.
      METHODS: We develop a state-transition Markov model of how individuals move
      between different health behaviour states over time. We simulate hypothetical
      data to describe the costs and health benefits of the intervention, illustrate
      how the data collected in the ongoing randomized controlled trial can be used and
      demonstrate how incremental cost-effectiveness ratios are estimated. RESULTS: On
      the basis of the simulated (i.e. hypothetical) data, we estimate the cost per
      quality-adjusted life year. The estimate reflects the lifetime health and
      economic consequences of the intervention. DISCUSSION: The method used for the
      cost-effectiveness analysis described in this paper is appropriate for
      investigating whether interventions that change health behaviour in relation to
      chronic diseases represent good value for money as compared to alternative uses
      of scarce healthcare resources.

PMID- 17175654
TI  - The personal impact of rheumatoid arthritis on patients' identity: a qualitative
      study.
AB  - OBJECTIVE: To provide a detailed understanding of the direct personal experiences
      of living with rheumatoid arthritis (RA) and the impact of the illness upon
      patients' lives, to inform the improvement of clinical care and training. METHOD:
      A qualitative study was performed using data from semi-structured interviews with
      26 patients who live with RA, recruited at two outpatient clinics in south-east
      England. RESULTS: In addition to the physical impact of RA on patients' lives,
      their accounts gave detailed descriptions of how their identity was affected in
      relation to: (1) their private lives (e.g., difficulties in their relationships,
      or caring for others); (2) their public roles and responsibilities (e.g., in
      their paid work and in experiences of stigmatization or discrimination); and (3)
      their private and public domains (e.g., perceived change of physical appearance,
      alteration of self-image, and change or loss of social roles). Young patients (25
      45 years) did report some differences in their chronic illness experiences, but
      patients from black and ethnic minorities did not. DISCUSSION: The study
      highlights new findings which can facilitate more open communication between
      staff and patients on the personal impact of RA, on patients' coping strategies,
      and on the effects on their identity both in private and in public. This will
      allow multidisciplinary outpatient services to provide care more closely matched
      to the difficulties that are directly experienced by patients.

PMID- 17175655
TI  - Living with chronic hepatitis C means 'you just haven't got a normal life any
      more'.
AB  - OBJECTIVE: To explore psychosocial factors that impact on quality of life for
      people living with self-reported chronic hepatitis C. METHODS: A purposeful
      sample of 70 people who were self-identified as being hepatitis C virus (HCV)
      positive was recruited through a variety of institutions and community agencies.
      Semi-structured interviews were held with 12 groups and 21 individuals. A
      qualitative grounded-theory methodology was used for data collection and
      analysis. Experiences of physical and psychological symptoms, stigma and
      discrimination, and living with an infectious disease, were explored using
      matrices. RESULTS: Phenomena emerging from the data included previously
      undocumented illness 'attacks' that were associated with depressive symptoms and
      a perception of hepatitis C as fatal. Uncertainty related to disease progression
      and transmission of the virus were common experiences among participants. A
      universal experience was fear and anxiety about stigma and discrimination.
      DISCUSSION: The findings of this study indicate that chronic hepatitis C has a
      pervasive impact on quality of life with a complexity that has not been explored
      with quantitative research approaches. Primary healthcare professionals need to
      be alert to the psychological and social impacts of chronic hepatitis C and to
      avoid behaviours that lead to perceptions of stigma and discrimination. The
      research indicates a need for further investigation into the relationship between
      psychosocial factors, disease management and disease progression.

PMID- 17175656
TI  - Better safe than sorry--why patients prefer to stop using selective serotonin
      reuptake inhibitor (SSRI) antidepressants but are afraid to do so: results of a
      qualitative study.
AB  - BACKGROUND: Patients need to be informed not only about the effects and side
      effects of their prescribed antidepressants such as selective serotonin reuptake
      inhibitors (SSRIs), but also about the consequences of stopping treatment with
      this medication. However, the professional guidelines on how to inform patients
      about stopping are not well developed and no consensus has yet been reached. This
      study focuses on the dilemmas involved in continuing or stopping the use of SSRIs
      from the perspective of the users and explores why these dilemmas tend to be
      solved by continuing rather than stopping. METHODS: A qualitative study of the
      views of 16 SSRI users in The Netherlands was performed. Most interviews were
      conducted at the subject's own home, and all were tape-recorded with permission,
      and transcribed verbatim. The analysis is based on grounded theory, aiming at the
      systematic development of theories and hypotheses through the inspection of
      interview responses. Emerging themes were discussed and refined using the
      constant comparative method. RESULTS: The SSRI users in this study had reached a
      certain balance after a period of trial and error. Feeling good could mean doing
      without these medicines, but could equally be because of the continuing use of
      these medicines. The SSRI users explained that it would be normal to stop at some
      time in the future. Some tried to stop but did not succeed, because they
      experienced serious drawbacks, so they continued, although they feared addiction
      and hoped that they would be able to stop at a later date. Others had never tried
      to stop, but said that they would like to because it is not normal to stay on
      this treatment forever. However, they were afraid that they would lose the
      balance that they had achieved in living a normal life. To support their choice
      of continuing SSRI use, they presented reasons why, in their case, this
      continuation was necessary. They all feared or had experiences with drawbacks,
      and were concerned and uncertain because of contradictory professional and lay
      messages about stopping the use of antidepressants, especially SSRIs. The fear
      and uncertainty about stopping without sufficient guidance were stronger than the
      fear and uncertainty about continuing. Users tended to stay on the safe side:
      better safe than sorry. DISCUSSION: The fact that users mentioned their arguments
      for continuing so explicitly implies that they regarded their SSRI use as
      problematic and ambivalent. They feared that there would be problems in stopping,
      and mentioned disagreements on this subject among professionals and in the media.
      Users saw doctors as important in tackling their fears. Doctors could play an
      active role in the process of discontinuation, but they have to be aware that as
      soon as users lose their balance and are unable to live a normal life they will
      probably decide to continue. Greater agreement on guidelines is needed to support
      doctors in this matter, when both the patient and the doctor have decided to stop
      treatment.

PMID- 17175657
TI  - Managing chronic fatigue syndrome in U.K. primary care: challenges and
      opportunities.
AB  - Calls for the treatment of chronic fatigue syndrome (CFS) in primary care have
      been based largely on considerations of the availability and accessibility of
      resources rather than with reference to a firm evidence base. Treatments such as
      cognitive-behavioural therapy and graded exercise therapy, which have proven
      effective for CFS in secondary and specialist care settings, have not been
      adequately tested in primary care. There are several factors that may affect the
      generalizability of such treatments. Patients seen in primary care may differ
      from those seen in secondary care, in terms of both illness beliefs and social
      characteristics, and these factors need to be taken into account when developing
      and adapting treatments for primary care. While some primary care physicians
      experience difficulties in the diagnosis of CFS, we argue that early and
      authoritative diagnosis and the provision of a tangible explanation for patients'
      symptoms are likely to be beneficial. Because of the scarcity of qualified
      specialist therapists, we need to train primary care practitioners to deliver
      treatments, and we need more research into the feasibility and effectiveness of
      doing this. Finally, the primary care setting offers opportunities for the guided
      development of patient self-help approaches.

PMID- 17175658
TI  - COPD therapeutics: picking the low-hanging fruit.

PMID- 17175659
TI  - Interaction between cigarette smoke and mycoplasma infection: a murine model.
AB  - Cigarette smoke has a major impact on health issues worldwide. Although genetics
      certainly is a factor in the sensitivity to cigarette smoke, other lung
      environmental factors, such as infection, potentially could interact with
      cigarette smoke to induce inflammatory changes associated with various diseases.
      Four groups of BALB/c mice (smoking only; smoking + M. pneumoniae infection;
      mycoplasma only; saline control) were studied for eight weeks to determine the
      interactive outcomes of inflammation and structural changes in the smoking plus
      mycoplasma group. This group did have significantly higher amounts of neutrophil
      degranulation in the outer airway wall area (smooth muscle to alveolar
      attachments) (p = 0.03) and mRNA expression of matrix metalloproteinase-9 (p=
      0.045). Although there was not a significant difference in alveolar tissue
      elastin between the groups, the smoking plus mycoplasma group had a level
      approximately 20% below the other groups. Even in this relatively short duration
      study, it appears that an infectious process can interact with cigarette smoke to
      produce a destructive type of inflammatory response (activated neutrophils and
      metalloproteinase-9) seen in the outer airway wall area.

PMID- 17175660
TI  - The effect of exercise on peripheral muscle in emphysema: a preliminary
      investigation.
AB  - Emphysema has been associated with loss of aerobic muscle fibers and decreased
      blood supply. However, when these changes begin and whether exercise can prevent
      these changes is unknown. The purpose of this study was to examine peripheral
      muscle at different time points during the development of emphysema and to
      determine the additional effects of muscle activity. In a series of 3
      experiments, emphysema was induced in hamsters. Exercise was simulated through
      surgical overload (OV) of the plantaris muscle of one leg. Animals were
      sacrificed at 1, 3, and 5 months following emphysema induction. Fiber type
      composition and capillary-to-fiber ratio (CFR) were determined. There were no
      significant changes in fiber type composition in the 1-month group. A significant
      increase in type IIA fiber composition (mean 72.0 vs. 54.5%) and decrease in type
      IIB fiber (mean 13.3 vs. 28.1%) was seen in the non-overloaded muscles following
      3 months. In the 5-month group, there was a significant decrease in percentage of
      type I fibers (mean 14.7 vs. 28.0%). There were no significant differences in
      fiber type composition in the OV limb, regardless of duration. The CFR was
      significantly lower in the OV limb after 5-months of emphysema (mean 0.92 vs.
      1.55 cap/fiber). Muscle overload prevented emphysema-associated changes in fiber
      type composition, but not in CFR. Peripheral muscle is affected early in the
      course of emphysema and chronic overload may play an important role in preserving
      normal muscle composition.

PMID- 17175662
TI  - Isolated bronchi of patients with COPD show decreased histamine responsiveness
      compared to smokers with normal lung function.
AB  - This study compared airway responsiveness in vitro, as measured in isolated
      bronchi, with responsiveness in vivo in patients with COPD and smokers with
      normal lung function. In 9 patients with COPD (mean (range) FEV, 55 (30-78)
      %predicted) and 8 smokers with normal lung function (FEV1 101 (89-117)
      %predicted), who underwent surgery for lung cancer, responses to inhaled
      histamine and salbutamol were assessed before surgery. Bronchial specimens of 1-4
      mm internal diameter were studied in the organ bath and histamine concentration
      response curves assessed. All patients with COPD and none of the control
      individuals were hyperresponsive to inhaled histamine. Five patients with COPD
      and no control patient showed a bronchodilator response to salbutamol. Opposite
      to these findings, bronchial rings in the organ bath demonstrated a rightward
      shift of histamine concentration-response curves in COPD compared to controls, (p
      < 0.005). Accordingly, pED50 but not Emax differed statistically (p = 0.0016)
      between groups, mean+/-SEM values of pED50 in COPD (controls) being 4.67+/-0.08
      (5.29+/-0.15) and of Emax 672+/-86 (772+/-120) mg. Patients with COPD showing
      hyperresponsiveness to inhaled histamine demonstrated lower responsiveness of
      their isolated bronchi compared to smokers with normal lung function. This
      suggests that in vivo hyperresponsiveness is based on other mechanisms than
      alterations in smooth muscle physiology.

PMID- 17175661
TI  - Multi-center study: the biochemical efficacy, safety and tolerability of a new
      alpha1-proteinase inhibitor, Zemaira.
AB  - Augmentation therapy with a plasma derived alpha l-Proteinase Inhibitor (alpha1 
      PI) has been demonstrated to be effective in restoring serum Alpha1 -antitrypsin
      (AAT)* levels in individuals with AAT Deficiency (note: alpha1 PI and AAT are
      synonymous). The objective of this study was to demonstrate that the steady-state
      trough serum alphal-PI levels, achieved by a new plasma derived alpha,-PI
      (Zemaira, study drug, ZLB Behring LLC, King of Prussia, Pennsylvania, USA), were
      bioequivalent to those achieved by the currently available alpha-PI therapy,
      Prolastin (control drug, Bayer Corporation, Berkeley, California, USA), and
      maintained weekly trough serum antigenic alpha1-PI levels above the protective
      threshold of 11 microM. This multi-center, controlled study randomized a total of
      44 subjects to receive either study or control drug for a 10-week double-blind
      phase. The control group was then crossed over to receive the study drug for the
      remainder of the study (14 weeks). The difference in mean trough serum antigenic
      alpha1-PI level between the treatment groups was 1.45 microM (90% CI-2.77, 
      0.13), signifying bioequivalence. The mean trough serum antigenic alpha1-PI level
      in the study drug group was greater than the therapeutic threshold of 11 microM,
      achieving a level of 17.7 microM during the steady-state period. Treatment
      related adverse events (AEs) were seen in 7% and 21% of study and control drug
      treated subjects, respectively. No documented viral transmission occurred. These
      results demonstrate that the new plasma derived alpha1-PI (Zemaira) is
      bioequivalent to the currently available product Prolastin, is well tolerated,
      and safe with respect to the risk of viral transmission.

PMID- 17175663
TI  - Relevant and redundant lung function parameters in discriminating asthma from
      COPD.
AB  - A relevant set of lung function parameters, derived from spirometry, flow-volume
      curves, diffusion capacity and bodyplethysmography, to discriminate asthma from
      COPD was established via logistic regression analysis. All new patients, referred
      to the outpatient clinic and later defined as asthma or COPD, underwent extensive
      lung function testing with reversibility testing. Logistic regression was used to
      calculate the probability to be a COPD or asthma patient. Selection of relevant
      parameters was done via 1] forward-, 2] backward-, 3] stepwise selection and 4]
      the best score method. All four methods were supplemented by bootstrapping to
      obtain a validated selection and estimation of the logistic regression
      parameters. The area under the ROC curve (mean+/-sd) for respectively the
      forward, backward, stepwise and best score selection method is 0.9348+/-0.0115,
      0.9346+/-0.0115, 0.9348+/-0.0115 and 0.9296+/-0.0121. The TLCO, VA and the
      postdilator MEF50, VC and PEF were selected as the most relevant parameters in
      discriminating asthma from COPD: they appeared most often as relevant
      discriminators in 500 bootstrapped samples: TLco was present in all bootstrapped
      samples and VA, postdilator MEF50, VC and PEF in resp. 70.8%, 46.2%, 42.8% and
      36.8%. Bodyplethysmography derived parameters turned out to be of limited value.
      Diffusion capacity testing and spirometry/flow-volume curve after administration
      of bronchodilators are the methods of choicewhen having to chose between asthma
      or COPD.

PMID- 17175664
TI  - Surface enhanced laser desorption/ionization (SELDI) time-of-flight mass
      spectrometry to identify patients with chronic obstructive pulmonary disease.
AB  - There are currently no blood tests to identify the majority of smokers at risk
      for chronic obstructive pulmonary disease (COPD). We used plasma protein profiles
      from surface enhanced laser desorption/ionization (SELDI) time-of-flight mass
      spectrometry to identify a panel of protein biomarkers that can distinguish
      patients with COPD from closely matched controls. Plasma was obtained from 30
      COPD subjects and 30 controls matched for age, sex, and smoking history. Plasma
      protein profiles were generated using Cu2+-immobilized metal affinity capture
      (IMAC) and strong anion exchanger (Q10) protein chips. Classification and
      regression tree (CART) analysis identified a panel of 5 biomarkers using the IMAC
      protein chip that could distinguish COPD patients from controls with sensitivity
      and specificity of 91.67% and 88.33%, respectively. The 10-fold cross-validation
      yielded 81.67% sensitivity and 81.67% specificity. This demonstrates the
      feasibility of using SELDI as a diagnostic test for COPD; however, larger cohorts
      will be needed to validate these biomarkers and determine their predictive value
      longitudinally.

PMID- 17175665
TI  - Systemic inflammation in COPD: is genetic susceptibility a key factor?
AB  - COPD is a multicomponent disease characterized by abnormal inflammatory response
      of the lungs to noxious particles that is accompanied by systemic effects like
      weight loss, muscle wasting, reduced functional capacity and impaired health
      status. A persistent low-grade systemic inflammatory response reflected by
      enhanced levels of acute phase proteins like C-reactive protein (CRP) and pro
      inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, is present in
      part of the COPD population. The production of inflammatory proteins is partly
      genetically determined. Several studies have shown that polymorphisms within
      genes coding for these inflammatory mediators may modulate systemic inflammatory
      responses. Among all of these genes, the TNF family (TNF-alpha, lymphotoxin (LT)
      alph and their receptors TNF-R55 and TNF-R75), interleukin (IL)-6 and CRP gene
      polymorphisms are the most prominent candidates. However, large carefully
      designed studies in well-characterized COPD cohorts are required to unravel the
      exact role of genetic background in the systemic component of this disease.

PMID- 17175666
TI  - A 26-year-old welder with severe non-reversible obstructive lung disease.
AB  - A 26-year-old white male, lifelong non-smoker presented with a history of
      increased shortness of breath, for approximately 1 year. He had a history of
      welding aluminum parts. He had evidence of partially reversible reactive airways
      disease with a non obstructive component as well. VATS biopsy revealed evidence
      of airway and parenchymal inflammation consistent with aluminum pneumoconiosis.
      Approximately 5-10% of COPD is attributable to non-smoking causes including
      occupational exposures. There are studies to suggest that the persistence of
      aluminum particulate may cause ongoing inflammation despite removal from
      exposure. It is possible that the persistence of particulate matter from tobacco
      smoke remaining in the lung may contribute to the persistent inflammatory
      response found in former smokers. Further study is required to examine the
      importance of this potential inflammatory mechanism both in occupationally
      exposed and in cigarette smokers. Reduction of certain particulate components of
      cigarette smoke may have implications for prevention of disease or at least
      disease progression in some COPD patients.

PMID- 17175667
TI  - Physical activity, spirometry and quality-of-life in chronic obstructive
      pulmonary disease.

PMID- 17175668
TI  - Sputum induction in COPD--it's safe, so now what do we do?

PMID- 17175669
TI  - Mortality after an emergency department visit for exacerbation of chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: To describe the mortality after emergency department (ED) visits for
      chronic obstructive pulmonary disease (COPD) exacerbation. DESIGN: Retrospective
      cohort study of ED patients with COPD exacerbation. Setting. Administrative data
      analysis. PARTICIPANTS: Patients age 55 and over who visited the ED during a 2
      year period with primary ICD-9 codes of 491, 492, or 496. MEASUREMENTS:
      Demographic characteristics, comorbid conditions, hospital utilization for COPD,
      and vital status. RESULTS: During the study period, there were 482 index visits
      with a median follow-up of 1,128 days (3.1 years). Demographic characteristics of
      the cohort were as follows: mean age 72 years, 56% female, 93% White, and 37%
      currently married. Mortality increased over time: 5% at 30 days, 9% at 60 days,
      11% at 90 days, 16% at 180 days, 23% at 1 year, 32% at 2 years, and 39% at 3
      years. At the end of follow-up, 220 (46%) patients had died. On multivariate
      analysis, independent predictors of mortality were increasing age (hazard ratio
      [HR] 1.3 per 5-year increase, 95% CI 1.2-1.4), having congestive heart failure
      (HR 1.6, 95% CI 1.2-2.1), having metastatic solid tumor (HR 3.3, 95% CI 2.0-5.5),
      and hospital utilization for COPD exacerbation during past year (HR 1.9, 95% CI
      1.4-2.6). CONCLUSION: The mortality rate after an ED visit for COPD exacerbation
      is quite high. Mortality is related to older age, specific comorbid conditions,
      and history of prior COPD exacerbations.

PMID- 17175670
TI  - Physical activity, spirometry and quality-of-life in chronic obstructive
      pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) has a high level of morbidity. There
      is limited information about levels of physical activity among community dwelling
      subjects with the disease and its association with lung function and quality of
      life. In this study, 176 subjects with COPD were recruited from general
      practices. Physical activity was measured over 7 days using pedometers, quality
      of-life using the St. George's Respiratory Questionnaire, and lung function using
      spirometry, 124 subjects, 60% male, aged 70 +/- 8 years were included in the
      analysis. Physical activity levels were low, median steps/day for males = 3621,
      IQR = 4247 and for females = 4287, IQR = 3063. Overall physical activity (median
      steps/day = 3716, IQR = 3682) was significantly associated with the forced
      expiratory volume in one second (r = 0.39, p < 0.001) and with St. George's
      Respiratory Questionnaire score (r = -0.28, p < 0.01). In conclusion, we have
      demonstrated that in a community-based sample of people with COPD, daily physical
      activity levels were low compared with usual levels reported for the general
      population. Physical activity was significantly associated with disease severity,
      measured by lung function, and quality-of-life.

PMID- 17175671
TI  - Safety of sputum induction in moderate-to-severe smoking-related chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Investigation of the safety of sputum induction in patients with
      moderate-to-severe chronic obstructive pulmonary disease (COPD) has been limited.
      OBJECTIVE: to evaluate this issue in 100 patients with a mean FEV1 of 1.2 (0.4)
      L. After 200 microg inhaled salbutamol, sputum induction was performed with
      inhaled saline in increasing and tailored concentrations (0.9% to 5%) until an
      adequate sample of sputum was obtained or the FEV1 fell by >20%. MAIN FINDINGS:
      Sputum induction was successful in 92% of occasions. The mean (SD) fall in FEV1
      was 13.5 (8.6)%. Five patients had a fall >20% but all recovered to 10% of
      baseline after inhaled salbutamol. The magnitude of fall in FEV1 correlated
      weakly with salbutamol reversibility (r = 0.37, p < 0.001), baseline FEV1/VC (r =
      -0.32, p = 0.001) and baseline FEV1% predicted (r = -0.36, p = 0.003) but not
      with age, smoking history or post-Salbutamol FEV1. Principle CONCLUSION: Sputum
      induction can be performed safely using a patient-tailored approach in patients
      with moderate-to-severe COPD, supporting its use in research and clinical
      practice.

PMID- 17175672
TI  - Case definitions for chronic obstructive pulmonary disease.
AB  - The objective of this study was to evaluate the definitions for classification of
      chronic obstructive pulmonary disease (COPD) recommended by the American Thoracic
      Society (ATS) and the Global Initiative for Chronic Obstructive Lung Disease
      (GOLD). Using data from the U.S. population-based third National Health and
      Nutrition Examination Survey (NHANES III), we compared the number of individuals
      in the U.S. population who met definitions of airflow obstruction based on the
      fixed ratio of FEV /FVC < 0.70 criterion and on the ATS lower 95% confidence
      limit (lower limits of normal LLN) criterion. Further, we evaluated the
      definitions in the context of physician-diagnosed obstructive airways diseases
      and respiratory symptoms. In comparison to the FEV1/FVC < LLN and FEV1 < 100%
      predicted definition, the fixed ratio-based definition for mild COPD
      underestimates airflow obstruction by 29% in 20-49-year-olds and overestimates it
      by 58% in 50-80-year-olds. In comparison to the FEV1/FVC < LLN and FEV1 < LLN
      definition, the fixed ratio-based definition for moderate COPD underestimates
      airflow obstruction by 31% in 20-49-year-olds and overestimates it by 37% in 50
      80 year olds. Based on our estimation, approximately 0.9 million (26%) of
      symptomatic individuals out of the 3.6 million U.S. adults aged 20-49 years who
      have airflow obstruction (FEV1/FVC < LLN and FEV1 < LLN definition) may have
      undiagnosed respiratory disease. In conclusion, using the FEV1/FVC < 0.70
      criterion will substantially under-diagnose airway obstruction in younger
      individuals and substantially over-diagnose COPD in older individuals.

PMID- 17175673
TI  - Inhaled recombinant alpha 1-antitrypsin ameliorates cigarette smoke-induced
      emphysema in the mouse.
AB  - In alpha 1-antitrypsin deficiency in humans, inadequately regulated activity of
      serine protease activity is responsible for the chronic lung tissue degeneration
      and irreversible loss of pulmonary function seen in those individuals with
      emphysema. Typically, disease symptoms in this patient population are exacerbated
      by cigarette smoke. Here we show that inhaled recombinant alpha 1-antitrypsin
      (rAAT) can provide significant protection against the development of emphysema in
      cigarette smoke-treated mice. As has been reported previously, cigarette smoke
      was seen to increase significantly the recruitment of neutrophils and macrophages
      into the lungs of these animals, leading to concomitant alveolar airspace
      enlargement and emphysema. In smoking animals treated for 6 months with inhaled
      rAAT, effects on lavage levels of neutrophils and macrophages were only moderate
      when compared with untreated animals. Furthermore, neutralizing antibodies to
      rAAT were generated in all rAAT-treated animals. Despite this, however,
      reductions in airspace enlargement of up to 73% were observed. These findings
      demonstrate that delivery of rAAT directly to the lungs of smoke-treated mice can
      inhibit lung tissue damage mediated by proteases, suggesting that rAAT inhalation
      therapy might represent a practical approach towards treating emphysema in
      humans, by modifying the course of the disease.

PMID- 17175674
TI  - Pathogenesis of bacterial exacerbations of COPD.
AB  - Acute exacerbations are significant events in the course of COPD. The
      pathogenesis of exacerbations was poorly understood, specifically, the role of
      bacteria was highly controversial. Recent observations have demonstrated that
      bacterial infection is involved in about half of the exacerbations. The
      predominant mechanism of bacterial exacerbation in COPD appears to be acquisition
      of new strains of bacterial pathogens from the environment that are able to
      establish infection in the tracheobronchial tree in COPD because of compromised
      innate lung defenses. These pathogens interact with airway cells, elicit an
      inflammatory response, which underlies the pathophysiology and symptoms
      characteristic of exacerbation. An immune response that can be mucosal, systemic
      or both develops to the infecting bacterial strain. This immune response contains
      the infectious process, could eradicate the infecting pathogen and prevent re
      infection with the same strain. However, because of antigenic diversity among
      bacterial strains, this immunity tends to be strain-specific rather than widely
      protective. Other mechanisms, including increase in bacterial load and
      interaction with other etiologies such as viruses, also could contribute to
      bacterial exacerbations. Improved understanding of the host-pathogen interaction
      in the airways in COPD will lead to novel approaches to prevention and treatment
      of exacerbations.

PMID- 17175675
TI  - Self-management of chronic conditions: the legacy of Sir William Osler.

PMID- 17175676
TI  - Self-management of chronic conditions: re-engineering patient-hood.

PMID- 17175677
TI  - Paternalism and the public's health.

PMID- 17175678
TI  - Self-management of chronic conditions: the long lead-up to the 'expert patient'.

PMID- 17175679
TI  - 'Walking like John Wayne': open-format diaries of people with knee pain and
      disability.
AB  - OBJECTIVE: To describe older people's everyday experience and context of living
      with knee pain and disability, and to explore the potential of open-format
      diaries in accessing these experiences. METHODS: This was a diary study, embedded
      in a larger mixed-method study. Ten people who participated in a qualitative
      interview study volunteered to keep an open-format diary over a period of 1 week.
      RESULTS: Diaries provided current and historical details about people's lives and
      their health. The diaries set these experiences within the context of daily life,
      and combined description with reflection. Themes covered included: causes of
      pain, symptoms and treatments, consultations, and co-morbidity. DISCUSSION: Open
      format diaries allow insights into the complex and contextual experience of pain
      and disability, and because of the contemporaneous detail, can be helpful to
      clinicians' holistic understanding of the impact of knee pain on people's quality
      of life. This method provides descriptive material that complements survey and
      qualitative interview data.

PMID- 17175680
TI  - Effects of a brief computer-assisted diabetes self-management intervention on
      dietary, biological and quality-of-life outcomes.
AB  - OBJECTIVE: There is a need for practical, efficient and broad-reaching diabetes
      self-management interventions that can produce changes in lifestyle behaviours
      such as healthy eating and weight loss. The objective of this study was to
      evaluate such a computer-assisted intervention. METHODS: Type 2 diabetes primary
      care patients (n=335) from fee-for-service and health maintenance organization
      settings were randomized to social cognitive theory-based tailored self
      management (TSM) or computer-aided enhanced usual care (UC). Intervention
      consisted of computer-assisted self-management assessment and feedback, tailored
      goal-setting, barrier identification, and problem-solving, followed by health
      counsellor interaction and follow-up calls. Outcomes were changes in dietary
      behaviours (fat and fruit/vegetable intake), haemoglobin Alc (HbA1c), lipids,
      weight, quality of life, and depression. RESULTS: TSM patients reduced dietary
      fat intake and weight significantly more than UC patients at the 2-month follow
      up. Among patients having elevated levels of HbA1c, lipids or depression at
      baseline, there were consistent directional trends favouring intervention, but
      these differences did not reach significance. The intervention proved feasible
      and was implemented successfully by a variety of staff. CONCLUSIONS: This
      relatively low-intensity intervention appealed to a large, generally
      representative sample of patients, was well implemented, and produced improvement
      in targeted behaviours. Implications of this practical clinical trial for
      dissemination are discussed.

PMID- 17175681
TI  - Pain management in sickle cell disease.
AB  - OBJECTIVES: Sickle cell disease (SCD) is an inherited blood disorder
      characterized by recurrent 'crisis' pain, which is the most common reason for
      repeated hospital admission. The nature of this pain, however, is poorly
      understood, and the pain is often sub-optimally managed. METHODS: A focus group
      format, interpreted using thematic analysis, was used to gain a greater
      understanding of the barriers that SCD patients face in managing their pain and
      their perceptions of the treatment that they receive from healthcare
      professionals. RESULTS: Key issues emerging from the focus groups that adversely
      affected participants' pain management included: feeling isolated by their
      experience of 'crisis' pain, not being listened to, and limitations to social
      support networks. Specific issues relating to seeking medical care included lack
      of understanding about SCD by nonspecialist clinicians, feelings of being low
      priority due to the 'invisible' nature of their pain, and feeling mistrusted by
      medical staff when seeking analgesia. DISCUSSION: Feelings of isolation may drive
      maladaptive coping strategies and manifest in anger, aggression and active
      avoidance of service use. Suggested service improvements include the active
      targeting of isolated individuals in the form of pain discussion groups or self
      help groups, and greater provision of specialised services.

PMID- 17175682
TI  - A naturalistic study of ambulatory asthma severity and reported avoidant coping
      styles.
AB  - OBJECTIVE: To examine how the use of dispositional avoidant coping traits
      prospectively predicts ambulatory asthma severity in daily life. METHODS: An
      ecological momentary assessment (EMA) design enabled examination of stable coping
      styles across dynamic daily changes of ambulatory peak expiratory flow rate
      (PEFR), asthma symptoms and stress in the natural environment of patients with
      asthma. A community sample of 61 adults with asthma reported their typical use of
      avoidant coping styles and carried palmtop computers that alerted them to record
      their stress and symptoms five times per day for 1 week. RESULTS: Some aspects of
      dispositional avoidant coping predicted more asthma symptoms and worse PEFR.
      Denial and behavioural disengagement as typical coping styles predicted more
      symptoms and worse PEFR. Mental disengagement was unrelated to symptoms and PEFR.
      DISCUSSION: These data suggest that individuals with asthma who report typically
      utilizing avoidant coping may have worse health parameters in momentary reports
      when examined in their natural environments. Differences between avoidant coping
      styles emerged, suggesting the existence of moderating factors of coping
      effectiveness.

PMID- 17175683
TI  - Bridging the knowledge-action gap in diabetes: information technologies,
      physician incentives and consumer incentives converge.
AB  - The gap between current medical knowledge and its application in chronic disease
      management is especially apparent in diabetes care. Although research over the
      last decade has shown that adherence to standards of care can prevent or delay
      the onset of devastating diabetic complications, little more than one-third of
      patients achieve adequate glycaemic control. Obstacles to better care include
      'system' factors such as inadequate record-keeping and reimbursement policies
      that reimburse amply for illness but poorly for diabetes education and
      interventions via telephone and computer. Disparities in healthcare compound the
      difficulty among vulnerable populations in urban and rural areas. Emerging
      healthcare delivery systems that encourage payers, providers and consumers to
      improve diabetes care with the use of information technology and financial
      incentives are described in different health management settings.

PMID- 17175684
TI  - Molecular analysis of the SMN1 and NAIP genes in 60 Tunisian spinal muscular
      atrophy patients.
AB  - In this study we examined the deletion of SMN and NAIP genes in 60 Tunisian
      families. There were 35 patients with type I SMA. 18 with type II SMA. 6 with
      type III SMA and I with type IV SMA. The age of onset was before 6 months for
      type I, between 6 months and 2 years for type II, between 2 years and 17 years
      for type III and 30 years for type IV. Exon 7 of SMNI gene was homozygously
      deleted in 95% (57/60) of SMA patients. There was a higher frequency of
      homozygous absence of SMN1 in type I and type II (100% and 94% respectively) than
      in type III (66,7%). SMN1 exon 8 was undetectable in 88% (53/60) of patients. The
      case type II patient with homozygous deletion of SMNI exon 7 and not exon 8 was
      tested for the presence of a hybrid SMN gene. This patient showed in the second
      PCR a SMN1 exon 8 product by restriction site assay indicating that a gene
      conversion event had occurred. All parents' individuals retained one copy of
      their SMN1 gene. Exon 5 of NAIP gene was homozygously deleted in 58% (35/60) of
      patients (77% in type I (27/35), 27,7% in type II (5/18), 50% (3/6) in type III.
      No patient had a deletion in NAIP gene without a deletion in the SMN1 gene.
      Homozygous deletion of NAIP exon 5 was detected in 1 parent. Our results show
      that the incidence of NAIP deletion is higher in the more severe SMA cases.

PMID- 17175685
TI  - [Sensitization to pollen in the asthmatic child. A study of 86 cases].
AB  - This retrospective study was designed to determine the place of pollen
      sensibilization in asthmatic child and to assess its epidemiological and clinical
      characteristics. 86 from 638 asthmatic child were allergic to pollen and included
      in the study. The mean age was 4 years (extremes : 1-12 years). The mean age of
      first respiratory manifestations was 1 and half years. The male/female ratio was
      1.46. Asthmatic attacks was noted in 77% of cases, chronic cough was the only
      allergic manifestation in 16% of cases. Associated rhinitis or conjunctivitis
      were found in 55% of cases, atopic dermatitis was found in 4 patients (4.6% of
      cases). Atopic asthma was per annual in 78% of cases. Pollinic asthma was
      diagnosed in 51 child. Other sensibilization were found in 60% of cases. 26 child
      (32%) were allergic to pollen only and 18 child to sample pollen. The gramineae
      pollen sensibilization is the most common allergy, followed by olive tree and
      cypress tree and herbaceous pollens.

PMID- 17175686
TI  - [Cryosurgery for nose basal cell carcinoma. Series of 17 tumors].
AB  - Basal cell carcinoma (BCC) is the most common malignant tumour of the skin
      frequently located on the head and chiefly on the nose. Cryosurgery is one of the
      methods to treat BCC. OBJECT: To determine the efficacy of cryosurgery of 17 BCC
      of the nose in terms of recurrence rates and cosmetic results. RESULTS: 15
      patients were included with a median age of 73 years and a photo type III or IV
      in 86% of cases. Mean size of tumours was 12 mm. Lesions were chiefly located on
      the alae nasi (70.5%). Complications were few and minor. After an average follow
      up of 13.5 months, recurrence rate was about 5.8% (one case). Cosmetic results
      were good or excellent in 14 cases/17; only one patient had developed a notch of
      the nose. CONCLUSION: Cryosurgery is a rapid, of a low cost technique and chiefly
      with good oncological and cosmetic results.

PMID- 17175687
TI  - [Consultation of congenital heart diseases in pediatric cardiology in
      Mauritania].
AB  - OBJECTIVES: The aim of this study is to describe the epidemiological profile of
      congenital heart diseases in Mauritanian children. MATERIAL AND METHODS: Our
      population was composed of children referred by the different cardiologists of
      the country on the occasion of two missions of pediatric cardiologists in
      December 2001 and November 2002. All patients had physical examination, chest
      radiogram, electrocardiogram, and echocardiogram. RESULTS: There were 84 patients
      aged between 2 months and 16 years. Mean age was 6.1 +/- 5.0 years. Forty eight
      children (57.1%) were males and 36 (43.9%) females (sex ratio was 1.3).
      Ventricular septal defect (17%), tetralogy of Fallot (13%) and pulmonary stenosis
      (12%) were the predominant pathologiese. Surgery was initially indicated for in
      61 infants (73%), realized in 22 of them (26%) and considered out of date in 10
      patients (12%). CONCLUSION: Congenital heart diseases pose a major problem of
      treatment in Mauritania. They are dominated by the left to right shunts. The age
      of diagnosis is relatively late (6 years) exposing to the risk of complications.
      Therefore, a team of paediatric cardiologists on the spot and the setting up of
      cardiovascular surgery facilities are necessary.

PMID- 17175688
TI  - [Predictive factors of failure of intravenous corticosteroid treatment in acute
      severe colitis of Crohn's disease and ulcerative colitis].
AB  - We conducted a retrospective study on 78 cases of acute severe colitis (Crohn's
      disease in 51 cases, ulcerative colitis in 27 cases). Diagnosis of acute severe
      colitis was based on presence of Truelove's criteria and/or endoscopical gravity
      lesions. Failure of corticoid treatment was observed in 35 patients (45%). In
      overall patients, predictive factors of failure of intravenous corticoid
      treatment in univariate analysis are diagnosis of ulcerative colitis, number of
      bloody stool higher than 6/day. level of C-reactive protein lower than 25 mg/l.
      visibility of muscular mucosa at colonoscopy, absence of decrease in erythrocyte
      sedimentation rate for more than 50% of initial value at day 3 of treatment,
      absence of decrease in C-reactive protein for more than 50% of initial value at
      day 3 of treatment, and a lower duration of corticoid treatment. In multivariate
      analysis, independent predictive factors of failure of corticoid treatment are a
      number of bloody stool higher than 6/day (p=0.01 adjusted OR [CI95%]: 10.2 [1.15 
      72.06]) and a value of initial C-reactive protein lower than 25 mg/l (p < 0.0001
      adjusted OR [CI95%] : 3.25 [2.95 - 4.31]). In Crohn's disease, the only
      independent predictive factor of failure of corticoid treatment is an absence of
      decrease of C-reactive protein level for more than 50% of initial value at day 3
      of treatment (p = 0.001 adjusted OR [CI95%] : 0.79 [0.45-0.95]). Existence of
      these predictive factors allows the early identification of patients who would be
      suitable for second-line therapy.

PMID- 17175689
TI  - [Risk factors of side effects of antituberculosis drugs].
AB  - The aim of this study was to determine the side effects of standard
      antituberculosis therapy with isoniazid, rifampicin, pyrazinamide and
      streptomycine in patients treated for tuberculosis. One hundred eighty nine
      patients with proven tuberculosis, who initially received standard
      antituberculosis therapy, were retrospectively studied. Begaud and coll's method
      of side effects drugs imputability elaborated in 1999 was used in our study. Side
      effects related to therapy were present in 31.7% of the studied population.
      Gastrointestinal side effect was the most common (13.2%), isoniazid, rifampicin
      and pyrazinamide were often incriminated. The significant risk factors of
      hepatotoxicity were female gender (OR : 10.59) and concomitant hepatotoxic drugs
      (OR 6). Chocleovestibular toxicity was associated significantly with female
      gender (OR : 8.03) and diabetes mellitus (OR : 6.13). Patients aged above 50,
      proved to be at risk for pyrazinomide intolerance and females for streptomycine.
      The study did not reveal any susceptibility to isoniazid and rifadine
      intolerance.

PMID- 17175690
TI  - [Association hyperlipidemia and retinal hard exudates in diabetic retinopathy].
AB  - Diabetes mellitus is usually accompagned with dyslipidemia, which can be
      correlated with diabetic retinopathy (DR). The aim of the study is to determine
      the relation between DR and hyperlipidemia. We studied prospectively 64 diabetic
      patients classified into 2 groups: the first associated diabetics having
      dyslipidemia (n=34) and the second without dyslipidemia (n=30). The mean follow
      up was 11 months. We observed a high frequency of retinal hard exudates in
      diabetics with dyslipidemia in comparison with the second group (32% versus 10%).
      The control of dyslipidemia is recommended in diabetic patients.

PMID- 17175691
TI  - [Colorectal polyps in children. A study of 34 patients].
AB  - AIM: To assess the frequency and the clinical features of polyps of the colon and
      rectum in children. METHODS: A total of 34 patients (20 boys and 14 girls, mean
      age: 5.4 years) were enrolled in this 14-years retrospective study. Diagnosis was
      done for almost all patients by colonoscopy (n=8) or recto-sigmoidoscopy (n= 19).
      After endoscopic polypectomy, polyp's type is determined by histological
      examination. RESULTS: Minimal and relapsing rectal bleeding was the most frequent
      finding of polyps of the colon and rectum (85.3%) followed by spontaneous
      emission of polyp (n=3), rectal prolapses (n=2), chronic constipation (n=1) and
      abdominal pain (n=1). The polyp was unique in all cases and with a mean size of
      12 mm. The majority of polyps were localized in the rectum or sigmoid (97%) and
      were pediculate (81.2%). Endoscopic polypectomies concerned 26 polyps while two
      small polyps were left. Most of the polyps corresponded histologically to
      juvenile polyps (96.2%). The immediate post-op course was uneventful for 26
      children. CONCLUSION: Our study suggests that rectal bleeding is the most
      frequent finding of polyps of the colon and rectum in childhood. Outcome after
      endoscopic polypectomy is good.

PMID- 17175692
TI  - [Juvenile idiopathic arthritis and Lyme disease: a case report].
AB  - Lyme disease is a systemic infection due to Borrelia burgdorferi. Joint
      involvement in children, when primary phase is unknown, can be confounded with
      juvenile idiopathic arthritis. We report a case of a 16 years old girl, who
      developed at the age of 14 a bilateral and symetrical polyarthritis of big and
      small joints with fever and cutaneous eruption of trunk. No clinical improvement
      was seen under disease modified treatment. More biological investigations were
      performed, leading to the diagnosis of Lyme disease. Clinical recovery was
      obtained under adapted antibiotherapy, Hence Lyme serology must be performed when
      atypical polyarthritis appears in a child especially in an endemic region of
      borrelia burdogferi.

PMID- 17175693
TI  - [An uncommon trichoepithelioma: the giant solitary trichoepithelioma].
AB  - A case of giant solitary trichoepithelioma of the perianal region is described so
      to draw attention to this rare benign neoplasme and to discuss its clinical and
      histopathological chracteristics.

PMID- 17175694
TI  - [Recurrent hydatidiform mole. Case report of 9 successive molar pregnancies].
AB  - The recurrent hydatiform mole is rare, its frequency is lower to 1%. We report
      the observation of a 28 years old women. without antecedents of molar pregnancy
      in the family and without considerable pathological antecedents. She had 9
      successive molar pregnancies, without inset normal pregnancies and without living
      children. The delay of at least 1 year between the gestations has been respected
      in 6 pregnancies. The etiologic balance in particular the caryotypes of parents
      is normal. The authors debate the etiopathogenic and prognostic factors of this
      pathology.

PMID- 17175695
TI  - [Hemangiopericytoma of the lumbar spine].
AB  - Hemangiocytoma are rare malignant vascular tumor. Vertebral location is uncommun.
      They occur preferentially at the lumbo-sacrul spine with paravertebral extension.
      The features include spinal pains, para vertebral tumefaction and paresthesia.
      The CT and MRI scans can help to diagnosis which is histological. The treatment
      is surgical combined or no with radiotherapy. The pronostic is marqued by the
      recidive risk and metastases. We report a new case of vertebral
      hemangiopericytoma of the thoraco-lumbar spine with litteratur review.

PMID- 17175696
TI  - [Case report of isolated Crohn's disease of the stomach presenting as plastica
      linitis].
AB  - INTRODUCTION: Crohn's disease of the stomach is rare. There is nearly always
      concomitant disease in the small bowel or colon. Gastric involvement occurs
      rarely as an isolated entity. Upper endoscopy is sensitive for detecting subtle
      disease but more extended lesions can mimic neoplasms such us linitis. Exegese: A
      74-year old female was admitted to hospital with abdominal pain, vomiting and
      weight loss. Upper endoscopy and radiology aspects was suspicious of gastric
      linitis. Multiple endoscopic biopsies of the stomach showed one granuloma,
      chronic inflammation and Helicobacter Pylori. Because of the importance of
      obstructive syndrome, the patient underwent surgery. The resected stomach
      concluded to a Crohn's disease. CONCLUSION: Through this observation, we review
      clinical characteristics, diagnostic difficulties and treatment options of
      Crohn's disease of the stomach.

PMID- 17175697
TI  - [Placenta praevia percreta with bladder invasion: a life-threatening pregnancy
      complication].
AB  - Placenta percreta is characterized by the penetration of trophoblast through the
      myometrium and peritoneum. This invasion may also involve adjacent structures.
      This condition is the most serious of placental implantation anomalies. It is a
      rare but life-threatening complication of pregnancy. We present a case of
      placenta praevia percreta with involvement of the bladder, discuss the
      particularities of the diagnosis and management, and review the literature.

PMID- 17175698
TI  - [Hysterosalpingography in the assessment of tubal patency].
AB  - A major cause of infertility in women is occlusion of fallopian tubes.
      Hysterosalpingography (HSG) and laparoscopic chemoperturbation are the two
      traditionnal diagnostic options for tubal assessment. Recently hysterosalpingo
      contrast sonography (HyCoSy), an ultrasound-based technique that uses as a
      contrast agent fluid injected into the fallopian tubes via the uterine cavity, is
      gaining importance as an alternative procedure. The aim of this study is the
      analysis of several technic and semiologic aspects of HyCoSy. RESULTS: advantges
      and limits are discussed throughout a review of literature. HyCoSy is a well
      tolerated outpatient technique. When performed by experienced operators, it servs
      as a valable first line screening test of tubal patency in low fertility women.
      It can confirme that tubes are patent and permits to select patients who need
      more invasive procedures.

PMID- 17175699
TI  - Emergence of chikungunya virus in Indian subcontinent after 32 years: A review.
AB  - An outbreak of chikungunya virus is currently ongoing in many countries in Indian
      Ocean since January 2005. The current outbreak appears to be the most severe and
      one of the biggest outbreaks caused by this virus. India, where this virus was
      last reported in 1973, is also amongst affected countries. Chikungunya virus has
      affected millions of the people in Africa and Southeast Asia, since it was first
      reported in 1952 in Tanzania. Even then, natural history of this disease is not
      fully understood. The intra-outbreak studies, point towards recent changes in the
      viral genome facilitating the rapid spread and enhanced pathogenecity. The
      available published scientific literature on chikungunya virus was searched to
      understand the natural history of this disease, reasons for the current outbreak
      and the causes behind re-emergence of the virus in India. The paucity of the
      scientific information on various epidemiological aspects of chikungunya virus
      threatens off an epidemic as control of spread of virus might be difficult in the
      absence of appropriate knowledge. There is an immediate need of the research on
      chikungunya virus, for an effective vaccine besides strengthening the existing
      diagnostic laboratory facilities. The current outbreak can also be taken as a
      lesson for establishment of a system for continuous surveillance of diseases,
      considered disappeared from the countries. The re-emergence and epidemics are
      unpredictable phenomena but the impact of such events can be ameliorated by
      appropriate knowledge and by being in the right state of preparedness.

PMID- 17175700
TI  - A double blind, randomised placebo controlled trial of rifampicin with omeprazole
      in the treatment of human cutaneous leishmaniasis.
AB  - BACKGROUND & OBJECTIVES: This study was conducted on 50 patients of Anthroponotic
      cutaneous leishmaniasis (oriental sore) to assess the efficacy of rifampicin and
      omeprazole through a double blind, randomised placebo control study. METHODS: The
      diagnosis of Anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania
      tropica was done by demonstration of Leishmania tropica (LT) bodies from the
      painless, dry ulcerative lesion. Each patient was assessed clinically in the
      beginning of the study, at the end of 2,4 and 6 weeks and all observations were
      compared in both the groups. Twenty-five patients received rifampicin with
      omeprazole (Group A) whereas other 25 patients received placebo (Group B) for a
      period of six weeks. RESULTS: Altogether 23 cases in group Aand 21 cases in group
      B completed the study. About 16 (69.7%) cases in group A and 3 (14.29%) cases in
      group B had complete healing, whereas 3 patients (13.04%) of group A and 4
      patients (19.05%) of group B had partial response and 4 patients (17.93%) of
      group A and 14 patients (66.67%) of group B had no response at the end of study.
      The difference of two groups was statistically highly significant (p < 0.00025).
      All patients tolerated the drug and placebo very well and no side effect was
      reported. INTERPRETATION & CONCLUSION: In our opinion rifampicin and omeprazole
      is a highly effective, less toxic and cheaper alternative for the management of
      cutaneous leishmaniasis.

PMID- 17175701
TI  - Estimating the relapse risk of Plasmodium vivax in Iran under national
      chemotherapy scheme using a novel method.
AB  - OBJECTIVES: This study aimed to estimate the relapse risk of Plasmodium vivax
      under national chemotherapy scheme using a novel method, and assessed its pattern
      in Kahnooj, a malaria endemic area in Iran. METHODS: The authors traced repeated
      episodes of malaria attack between 1994 and 2001 and then, estimated the risks of
      secondary attack of P. vivax, classified by the species in their primary attack.
      It is suggested that the difference between the secondary attack rate in those
      who were infected by P falciparum and P. vivax in their primary attack may
      estimate the P. vivax relapse rate indirectly. RESULTS: This method showed that
      the relapse risk of P. vivax with in one and two years after the primary attack
      were 16.8 and 24.5% respectively. The risks of relapse before three or after 18
      months were very low. INTERPRETATION & CONCLUSION: The relapse pattern of P.
      vivax was compatible with the dominant pattern in most of the temperate areas. In
      addition, the relapse risk was very close to the estimated relapse risks in
      clinical trials on anti-relapse drugs. Therefore, we concluded that the anti
      relapse therapy in the study area was effective; also, this method may estimate
      the relapse risk of P. vivax accurately.

PMID- 17175702
TI  - Impact of urbanisation on bionomics and distribution of malaria vectors in Lagos,
      southwestern Nigeria.
AB  - BACKGROUND & OBJECTIVES: The patterns of annual, rainfall as well as average
      daily temperature have not changed drastically in the study area since 1960 when
      detailed baseline entomological surveys were carried out. However, the increase
      in human population from 1.2 to 10 million has resulted in both expansion of land
      and tremendous ecological and environmental change. This has led to drastic
      changes in vectors' densities as well as species' composition while the preferred
      larval habitat of malaria vectors has shifted to water reservoirs. A longitudinal
      study was carried out to investigate the impact of urbanisation on bionomics and
      distribution of malaria vectors in Lagos, a mega city in Nigeria. METHODS:
      Mosquitoes were collected indoors and outdoors using WHO standard techniques in
      the selected areas between January and December 2000. Specimens were identified
      using the morphological keys and PCR assays. ELISA tests were used for Plasmodium
      falciparum sporozoite infection. RESULTS: The Anopheles gambiae species-specific
      PCR identified 56% (435/777) of the An. gambiae s.1. as An. gambiae s.s. and 44%
      (342/777) as An. arabiensis. The molecular M and S forms represented 35.3 and
      64.7% of the An. gambiae s.s. population, respectively. The An. funestus species
      specific PCR identified 60% (239/401) of the An. funestus group as An. funestus
      s.s. and 40% (162/401) as An. rivulorum. The biting activity of An. funestus s.s.
      both indoors and outdoors attained a peak at 0200 and 2200 hrs, respectively,
      with a significant increase in the "pre-bed time" collections indoors (Chi2 =
      6.15, df = 1, p < 0.05) and outdoors (Chi2 = 6.28, df = 1, p < 0.05). The overall
      outdoor collection was significantly higher (Chi2 = 28.23, df =3, p < 0.05) than
      that recorded indoors. The overall sporozoite rates for An. gambiae s.s., An.
      arabiensis and An. funestus were significantly different in both localities (Chi2
      = 0.58, df = 2, p < 0.01). Infection rates in both indoor and outdoor collections
      were also different statistically (Chi2 = 0.67, df = 2, p < 0.01). INTERPRETATION
      & CONCLUSION: Large number and species of anopheline mosquitoes collected in the
      study area may be associated with the availability of aquatic breeding sites. A
      phenomenon leading to an increase in man-vector contact and a high level of risk
      to the crowded urban population is observed.

PMID- 17175704
TI  - Comparison of different diagnostic techniques in Plasmodium falciparum cerebral
      malaria.
AB  - BACKGROUND & OBJECTIVES: Plasmodium falciparum cerebral malaria remains a major
      health problem in India. The efficacy of treatment of cerebral malaria lies in
      its early diagnosis through rapid diagnostic methods. ParaSights-F test detects
      HRP-2 antigen secreted by parasitised red blood cells and quantitative buffy coat
      assay (QBC) is examination of buffy coat for the presence of malarial parasite
      stained with acridine orange. This study was performed to evaluate the
      effectiveness of ParaSight-F test and QBC assay as diagnostic methods in the
      patients of cerebral malaria. METHODS: Fifty clinically diagnosed patients of
      cerebral malaria were included in the study. ParaSight-F test, QBC and
      conventional blood smear examination was done. Patients who were in coma and
      there were no obvious features of bacterial or viral etiology were investigated
      for cerebral malaria by these diagnostic methods. RESULTS: ParaSight-F test, QBC
      and peripheral blood smears were examined. Patients were followed-up for signs of
      clinical recovery. ParaSight-F test was positive in 47 patients, QBC in 46 while
      blood smear examination was positive in 28 cases. INTERPRETATION & CONCLUSION:
      Sensitivity and specificity of ParaSight-F test were found to be 96.6 and 94%
      while QBC showed 97.8 and 100% respectively. ParaSight-F test and QBC were found
      to be novel methods for diagnosis of cerebral malaria especially in the cases
      where diagnosis can not be made by conventional blood smear examination due to
      low parasitaemia. These rapid diagnostic methods help in early therapeutic
      intervention.

PMID- 17175703
TI  - Introduction, transmission and aggravation of malaria in desert ecosystem of
      Rajasthan, India.
AB  - BACKGROUND & OBJECTIVES: Malaria is an important public health problem in
      northwestern desert part of Rajasthan. Since desert malaria is seasonal or
      unstable, there is a need to study its epidemiology in the totality to address
      factors like how malaria is introduced into desert every year and what are desert
      specific transmission risk factors leading to epidemics? METHODS: Twenty-six
      villages in irrigated, semi-irrigated and non-irrigated settings of the desert
      have been selected. Periodic investigations were undertaken in all the seasons
      from 2001 through 2002 to determine causes of introduction of disease, the
      factors involved in its transmission and the epidemic risk factors. Standard
      methods/procedures for mosquito collection, preservation and identification and
      for parasitological studies were employed. Rainfall data were analysed and
      correlated. RESULTS: Importation of malaria infection through individuals was the
      major cause of introduction of disease in all the 12 villages showing some
      initial load of infection. Areas having higher population of cattle in relation
      to humans (human to cattle ratio of 1:25) had less transmission of disease (ratio
      of primary to secondary cases 1:3) as compared to relatively less cattle (human
      to cattle ratio 1:3) resulting into high transmission of disease with 1:47 ratio
      of primary to secondary cases. Introduced through migration, prospective
      transmission of malaria was observed as a resultant interaction of density of
      three components namely malaria cases, vector density and cattle to human ratio.
      Rainfall more than average when coupled with more cases of imported malaria leads
      to the eruption of malaria epidemics. INTERPRETATION & CONCLUSION: Importation of
      malaria cases was the major cause of seasonal introduction of malaria in the
      desert. This initial or primary parasitic load available in a village leads to a
      particular transmission quantum depending upon the density of vectors, human and
      cattle population at a particular time. Areas with more imported cases when
      coupled with profuse vector population lead to epidemic malaria situations in the
      desert.

PMID- 17175705
TI  - Detection of plasmodium falciparum infection in anopheles mosquitoes from
      Keonjhar district, Orissa, India.

PMID- 17175706
TI  - Co-infection between tuberculosis and malaria: A consideration on interaction of
      molecules and pathogenesis.

PMID- 17175707
TI  - A survey of anopheline mosquitoes and malarial parasite in commuters in a rural
      and an urban area in West Bengal, India.

PMID- 17175708
TI  - Dengue haemorrhagic fever in pregnancy: Appraisal on Thai cases.

PMID- 17175709
TI  - Plasmodium ovale--a case report from Gujarat.

PMID- 17175710
TI  - [The prevention and control of hospital infection: a case study with nurses].
AB  - A descriptive case study carried out with nurses. Its main purpose is getting to
      know the physical and administrative structure of the hospitals in this area, as
      well as their averal policy regarding the nurses'action in the prevention ans
      control of hospital infection. Twenty-eight nurses participated. Data was
      collected through the observation of the physical area of the hospitals, the
      reading of the evaluation and inspection documents from the Health Surveillance
      Department from the 12h CRS and through interviews conducted with the nurses.
      Final analysis showed the need of a deep reassessment of the daily actions for
      the prevention and control of hospital infections in these hospitals so as to
      promote health, reduce the hazards to inpatients and guarantee safety for both
      health professionals and patients.

PMID- 17175711
TI  - [The family living with Down syndrome patients in the perspective of Humanistic
      Theory].
AB  - The objective of this study was to socialize the process of coexistence of the
      family of the bearers of syndrome of Down based in the Humanistic Theory of
      Paterson and Zderad. The study was realized with a research of descriptive
      exploratory character, with a qualitative approach and participant observation.
      It was accomplished in APAE/ Sobral-CE, with the use of group dynamics and a
      guided interview for collection of data. The results showed us that the parents
      don't have difference between a normal son and a special one; the treatment is
      the same, with a lot of love, affection, understanding and respect, however a lot
      of times they find some difficulties in taking care, as the communication and the
      feeding. We also observed that the family is very important, necessary, so that
      the coexistence with the bearer becomes more and more natural in spite of a
      society that, a lot of times, still has prejudice.

PMID- 17175712
TI  - [Use of a tool for record of child and family health information and nurse's
      practice in basic health care].
AB  - Children's growth and development process is influenced by different factors and
      the family is considered as its primary context. This descriptive study aims at
      describing the elaboration and use of a tool in basic health care, aimed at
      observing, interviewing and registering data of children and families in nursing
      practice. Study participants were 10 families with children between 0 and 24
      months of age. Data were collected by consulting patient records, interviews and
      observation. Based on a previous bibliographic review, an instrument was
      constructed and applied, which revealed possibilities for the systematization of
      nursing care, information organization and better health interventions.

PMID- 17175713
TI  - [An educative practice of sensitization to ionizing radiation exposition with
      health professionals].
AB  - This study present a nursing care practice whose objective is to sensitize health
      professionals of neonatal intensive care unit about the risk of exposition to
      ionizing radiation, aiming to optimize the radiological protection. The Operative
      Italian Model (OIM) was the main theoretical and methodological reference which
      guided this practice, carried out with twelve participants in a public hospital
      in Floriandpolis-SC, Brazil. The results demonstrated that health professionals
      are exposed to ionizing radiation, especially for not being aware of the
      recommendations already included in the legislation.

PMID- 17175714
TI  - [Applying recommendations of the Braden's scale and preventing pressure ulcers-
      evidences for nursing care].
AB  - The occurence risk of pressure ulcer (PU) by the patient is questioned as well as
      the validity of nursing care applying the Braden's scale to verify the evidences
      of this care in the incidence of the PU. The method of biophysiologic measures in
      ICU patients was used. It was found 11 patients with PU, in a 26.83% incidence.
      The majority (57.1%) of ulcer was in stage I. Patients with PU have lower scores
      than the ones without PU, showing sensitivity to predict the PU risk. It was
      concluded that: the evidence of nursing care was demonstrated by the density of
      47.12% for the patients without PU, the incidence of PU was lower than rates of
      other UCUs; preventive nursing care reduces the PU.

PMID- 17175715
TI  - [Nursing diagnoses in patients after heart catheterization--contribution of
      Orem].
AB  - Sectional study of multiple cases involving 30 patients after heart
      catheterization aiming to establish the nursing diagnoges according to the North
      American Nursing Diagnoses Association (NANDA). The method of data collection was
      the Nursing Process based on the Self-care Deficit Theory. Twenty-five different
      nursing diagnoses had been established. All patients presented Impaired tissue
      integrity, Risk of infection, Pain incisive in the area inguinal, Injured
      physical mobility, Self-care deficit related to personal hygiene, and Risk of
      organic renal lesion. It has been concluded that the Self-care Deficit theory
      allowed the classification of all nursing diagnoses according to NANDA. It
      contributed to the nursing assistance individualization, humanization, and
      qualification. Beyond advance self-knowledge, self-control and patient
      participation on his/her self-car.

PMID- 17175716
TI  - [Hospital humanization: professional satisfaction in a pediatric hospital].
AB  - It was aimed at evaluating the professionals' satisfaction of a municipal
      pediatric hospital of Fortaleza with relationship to the humanization of the
      attendance in the hospital, as National Program of Humanization of the Hospital
      Assistance extolled by ministry of Health. The descriptive study had as sample 38
      professionals. The data collection was carried out by a questionnaire, being the
      data presented in tables. Interaction was detected between the administration of
      the hospital and the professionals by internal discussions to evaluate the
      service. They consider the work environment is confortable for their work
      practice, therefore some improvement was indicated. The support for the
      professionals was suggested as an improvement point. The professionals suggested
      trainings, improvement of the atmosphere of the hospital and quality of the
      attendance. It is expected that this study supplies subsidies for the planning of
      actions favorable for the humanization of hospital assistance.

PMID- 17175717
TI  - [People with diabetes mellitus: their care and treatment choices].
AB  - Study based on qualitative research, from an interpretative perspective. Its
      objective was to understand the therapeutic itinerary of people with Diabetes
      Mellitus who search for different care and treatments within the different
      subsystems of health care. The data was collected through in-depth interviews and
      focus groups. As a result of the data analysis therapeutic modalities were
      identified, the evaluation of the care process and health treatment and the
      therapeutic journey in the three subsystems. The person with Diabetes Mellitus
      needs to reevaluate their process of living. Thus, the person circulates through
      various therapeutic modalities until they perceive that (or those) which are most
      convenient for them. This also applies to how said care or treatment becomes
      integrated into their day-to-day.

PMID- 17175718
TI  - [Maternal mortality: socio-demographic and causal profile].
AB  - This study had as an objective to evaluate the maternal death in the city of
      Porto Alegre (RS) at the years of 1999, 2000 and 2001. Made part of the
      population all the women between 10 and 49 years old who died during the
      pregnancy, on birth or one year from these events. The data was collected from
      the Information Team about Mortality (Equipe de Informacao sobre Mortalidade) and
      from the Municipal Council of Studies and Prevention of the Maternal Deaths of
      Porto Alegre (Conselho Municipal de Estudos e Prevencao das Mortes Maternas de
      Porto Alegre). The most frequent causes of the maternal death were: infection
      post-birth (15%) and hypertensive trouble of the pregnancy (15%), followed by
      illness of the circulatory system/Heart Attack (13%), septicemy (10%) and the
      causes related to the Acquired Immune Deficiency Syndrome (AIDS) (8%).

PMID- 17175719
TI  - [Body techniques in a group of pregnant women: the experience of the subjects].
AB  - The objective this study was evaluate the effectiveness of the use of the body
      techniques in a group of pregnant women according to the experience of the
      subjects. They were all interviewed before the end of the group developed in a
      University Hospital. The descriptive categories of the experience were: the body
      techniques relieved the pregnancy discomforts, had encouraged the participation
      in the sessions and had been evaluated positively; the use of body techniques in
      a group of pregnant women promoted selfcare of the members; body techniques
      intensified the link among the couples and gave conditions for the integration of
      the members; there are limitations in use of the body techniques in a group of
      pregnant women and in its applicability at home. The positive evaluation of the
      use of body techniques in a group of pregnant women justifies its recommendation.

PMID- 17175720
TI  - [Elaboration and validation of the nursing interview].
AB  - The purpose of this research was to elaborate and validate the instrument Nursing
      Interview to collect data related to nursing care based on the Orem theory. The
      contents of this instrument and the supporting guidelines were referred to
      referees who analyzed the concordance among them by applying Cochran's Chi-Square
      test, which revealed a statistically significant difference regarding objectivity
      but the great number of positive answers indicated that the instrument also dealt
      with pertinent aspects. The descriptive analysis of concordance related to the
      supporting guidelines demonstrated that only objectivity obtained 50% of negative
      responses, suggesting that changes were required. Finally, we may conclude that
      this instrument collects data related to self-care in a systematic manner.

PMID- 17175721
TI  - [Nursing diagnoses in cardiac surgery patients].
AB  - Exploratory and transversal research accomplished with postoperative patients
      outgoing coronary bypass. It was aimed at identifying nursing diagnoses according
      to Taxonomy II of NANDA and nursing interventions according to Nursing
      Interventions Classification, associating with the results of Nursing Outcomes
      Classification. The data were collected fom 22 patients using formularies and
      physical examination. The information made possible the identification of fifteen
      nursing diagnosis, according to Taxonomy II of NANDA. Among them, stand out: risk
      of infection; Risk of constipation; Deficit in self-care intimate hygiene and
      integrity of harmed skin. The study revealed being fundamental to develop studies
      about nursing diagnoses to direct analyses of problems that concern to the
      demanding patients of specific nursing actions, that contribute to the devepoment
      of the profession.

PMID- 17175722
TI  - [Communication in care: a fundamental task in nursing].
AB  - The research debates the communication as basic instrument of the attention,
      articulated to the dynamic of the care and of the attention in the hospital.
      Interviews had been made, participant observation and consult to promptuaries. It
      was applied dense description and thematic analysis. It was identified diverse
      forms of communication: verbal and nonverbal. It was stood out the form as the
      professional approached and communicated with the customer, printing more or
      little attention and affection. The interaction in the attention emerged of the
      meeting and colloquies among the professionals and customers, integrating them to
      the attention. The act of talk is basic in the attention. Either of technician or
      ludic content, the colloquy implies in communication, that holds interaction,
      language, gestures and cognition. From there its importance for the nursing, art
      and science of the attention.

PMID- 17175723
TI  - [The care of homeless person: reviewing the meanings of health-disease process].
AB  - This qualitative research had the objective of knowing the significance of the
      health-sickness-care process to homeless person and workers of a community center
      to homeless people on Sio Paulo city. The dates were collected by the interview
      with four homeless person and four workers. The interviews were separated in
      three categories: (1) the apprehension of the health - sickness-care process, (2)
      the caring of health in the street, (3) advices to survive in the street. The
      results showed that even with the difference of the homeless person, the street
      have a specific culture relative of the health-sickness-care person that need to
      be comprehend by nurses.

PMID- 17175724
TI  - [The relation between time and violence in the nursing work at emergency and
      urgency].
AB  - Believing that the organization form of work and the quantity of time given to
      the assistance work in the hospital can become a cause of violence that affects
      workers'and usuaries'life, this article analyzed the workers'perception about the
      time they have for their activities and the violence demonstration in the context
      of emergency and urgency work of a public hospital of Mato Grosso. It's a
      qualitative research done close to the members of the nursing staff, with data
      collected through participative observation and interviews. The data thematically
      analyzed revealed that the insufficient time makes part of the violence genesis
      at the nursing work and it is characterized as: classical, structural, repressive
      and alienation violence.

PMID- 17175725
TI  - [Accidents in childhood and adolescence: a bibliographic review].
AB  - This study aims at reviewing the literature on accidents among young under the
      age of 15. Throughout Brazil, lesions and poisonings are responsible for 5 to 6
      percent of total internments by the National Health System (SUS), generating 8
      percent of the total hospital internment expenses. Sweden and Italy are the
      countries that have the lowest mortality rates related to external causes among
      youngsters under the age of 15. The rates of Denmark, Germany and Japan are
      regarded as intermediate. France, Belgium, Austria and Canada are regarded as
      countries with high mortality rates related to external causes among youngsters
      under the age of 15. Brazil together with the United States, Portugal, Mexico and
      Korea are considered countries with very high mortality rates related to
      childhood accidents, needing preventive actions. Furthermore, studies reinforce
      the importance of recognizing the nature and reality of childhood accidents in
      order to form a diagnosis that helps elaborate and accomplish specific prevention
      policies.

PMID- 17175727
TI  - [Current perspectives in nursing informatics].
AB  - Nursing Informatics is the area of knowledge that studies the application of
      technological resources in teaching, in practice, in care, and in the management
      of care. Resources such as voice recognition, knowledge base, genoma project and
      even Internet have offered to Nursing a gama of possibilities for a better
      professional performance and better nursing care to the patient/client. This text
      reports and exemplifies how these resources are impacting and presenting new
      oportunities for teaching, research and specially for nursing care, still warns
      for the importance of humanized care in a high-tech scenario.

PMID- 17175726
TI  - [Ethical and bioethical issues disturbing nursing: REBEn's publications from 1970
      to 2000].
AB  - It was studied the ethical and/or bioethical issues published in the Revista
      Brasileira de Enfermagem (Brazilian Nursing Journal-REBEn) that disturbed the
      nursing in the period between 1970 and 2000. Tha aim was to identify in articles
      published in the REBEn, during the mentioned period, subjects related to the
      ethics/bioethics. To discuss the theoretical perspectives in which the authors
      base their arguments. The study was quantitative and qualitative, documentary or
      bibliographical type. RESULTS: in the last 30 years it had gradual increase in
      the number of the articles that debates ethical questionings. After 1984 appear
      the first study, with bioethics connotation, in which the author discourses on
      the interventions of nursing before the patient in imminent death, with the
      purpose to verify the relations between the personal and professional values of
      the nurse. Was Valdria Lunardi who used the bioethics term for the first time in
      1998.

PMID- 17175728
TI  - [Historical perspectives of the Genome Project and the evolution of nursing].
AB  - This article aims to draw a historical view of the main transformations that are
      happening in nursing after the completion of the Genome Project. We present
      current information about genetics, the Human Genome Project, genomic research
      and their interface within nursing practice, as well as vanguard proposals in
      various important research areas for nurses. Furthermore, we describe the
      emergence of a new specialization area in nursing, nursing in genetics, and the
      International Society for Nurses in Genetics, which standardizes its professional
      exercise. Finally, we present some recent research data, aimed at integrating
      genetics and, consequently, genomics in nursing teaching, research and care.

PMID- 17175729
TI  - [Aged victim of burns: identification of diagnosis and proposal of nursing
      interventions].
AB  - This case study aimed at identifying the Nursing Diagnosis (ND) in agreement with
      the taxonomy II of the North-American Nursing Diagnosis Association (NANDA) of a
      patient victim of burning of 2nd e 3th degrees and to elaborate the nursing
      interventions. Eight ND were identified being five with the presence of defining
      characteristics and related factors (real), and three of risk. Intervention
      proposal was elaborated starting by the needs related to the vital and
      physiologic signs, the base of human basic needs hierarchy. Finally, it was
      observed the relevance of nursing process applicability in the implementation of
      care and its need in daily nursinga activitiies.

PMID- 17175730
TI  - [Editors' note].

PMID- 17175731
TI  - Intermunicipal health care consortia in Brazil: strategic behavior, incentives
      and sustainability.
AB  - This article studies strategic behavior in municipal health care consortia where
      neighboring municipalities form a partnership to supply high-complexity health
      care. Each municipality partially funds the organization. Depending on the
      partnership contract, a free rider problem may jeopardize the organization. A
      municipality will default its payments if it can still benefit from the services,
      especially when political pressures for competing expenditure arise. The main
      result is that the partnership sustainability depends on punishment mechanisms to
      a defaulting member, the gains from joint provision of services and the overall
      economic environment. Possible solutions to the incentive problem are discussed.

PMID- 17175732
TI  - The Georgian healthcare system: is it reaching the WHO health system goals?
AB  - After the break-up of the Soviet Union, the country of Georgia suffered from
      intense civil unrest and socio-economic deterioration, which particularly
      affected the health sector. To remedy the situation, the government initiated
      health sector reform, which introduced major changes in healthcare financing in
      Georgia: the previously free healthcare model was replaced by social insurance,
      and patients were required to pay out-of-pocket for services not covered by
      insurance. This paper is an attempt to determine if the health system of Georgia
      is reaching the WHO health system goals of improved health status, responsiveness
      to patients' needs (consumer satisfaction), and financial risk protection as a
      result of health reforms.

PMID- 17175733
TI  - Good governance and sustainability: a case study from Pakistan.
AB  - OBJECTIVE: On the basis of a case study in Pakistan, the paper argues that good
      governance, characterized by transparency, accountability and meaningful
      community participation, plays a critical role in the sustainability of donor
      funded health systems projects in the public health sector. METHODS: The Family
      Health Project (FHP) (1992-1999), funded by the World Bank, has been used as a
      case study. Critical analysis of secondary data mainly obtained from the
      Department of Health (DoH) in the province of Sindh in Pakistan is the major tool
      used for the study. Data from other sources including the World Bank have also
      been used. RESULTS: The analysis reveals that the existing health care system
      could not fully absorb and sustain major "sociopolitical" thrusts of the project,
      meaningful community participation and "democratic" decision-making processes
      being the most important ones. The hierarchical structure and management process
      made it difficult to produce a sense of ownership of the project among all
      managers and the rank and file staff. The Provincial Health Development Center
      (PHDC) and District Health Development Centers (DHDCs) established by the FHP did
      not receive adequate financial and political support from DoH and the Ministry of
      Health to have much control of the project at the local level. Consequently,
      these Centers largely failed to institutionalize a continuing training program
      for district level health officials/professionals. Due to lack of political
      support, the District Health Management Teams (DHMTs) could not be
      institutionalized. Community participation in the DHMTs was symbolic rather than
      forceful. Improved coordination among all stakeholders, more stable and competent
      leadership, more meaningful community participation, greater devolution of
      project management to the district level, and better management of resources
      would have resulted in more effective and efficient implementation of the
      project. Based on these findings, the paper introduces a Sustainable Management
      Approach (SMA) as a tool that can be used to ensure the sustainability of health
      systems projects, particularly those funded by international organizations in
      developing countries. CONCLUSIONS: Good governance and a conducive organizational
      culture are important prerequisites for incorporating any new project within an
      existing system. This includes prior consensus building among all stakeholders, a
      meaningful and inclusive participatory planning, implementation and evaluation
      process involving communities, political commitment, and the identification and
      use of appropriate leadership for project management.

PMID- 17175734
TI  - Whither managerialism in the Italian National Health Service?
AB  - In the last decade, the Italian National Health Service has been characterized by
      the introduction of managerial concepts and techniques, according to the New
      Public Management paradigm. Recently, these reforms have been increasingly
      criticized. This article examines the implementation of managerialism in an
      attempt to evaluate its overall achievements and shortcomings. Overall,
      managerialism seems to have made good progress: managerial skills are improving;
      several management tools have been adapted to health-care and public-sector
      peculiarities; health-care organizations have adopted a wide range of technical
      solutions to fit their specific needs. At the same time, managerial innovations
      have often focused on structures as opposed to processes, on the way the
      organization looks as opposed to the way it works, on the tools it has as opposed
      to those it actually needs and uses. We thus suggest that research, training and
      policy-making should stop focusing on the technical features and theoretical
      virtues of specific tools and should redirect their emphasis on change
      management.

PMID- 17175735
TI  - Regulating private health insurance to serve the public interest: policy issues
      for developing countries.
AB  - Private health insurance plays a large and increasing role around the world. This
      paper reviews international experiences and shows that private health insurance
      is significant in countries with widely different income levels and health system
      structures. It contrasts trends in private health insurance expansion across
      regions and highlights countries with particularly important experiences of
      private coverage. It then discusses the regulatory approaches and policies that
      can structure private health insurance markets in ways that mobilize resources
      for health care, promote financial risk protection, protect consumers and reduce
      inequities. The paper argues that policy makers need to confront the role that
      private health insurance will play in their health systems and regulate the
      sector appropriately so that it serves public goals of universal coverage and
      equity.

PMID- 17175736
TI  - A new level of understanding. Health insurers are developing health literacy
      initiatives and taking steps to help consumers get clear information.
AB  - Education experts are issuing an important warning to their health care
      colleagues: Few Americans understand their health care information. That's the
      conclusion drawn from a National Center for Education Statistics (NCES) survey
      that assessed the health literacy of 19,000 adults, only to conclude that the
      nation's health literacy is dangerously low and may even become a health risk for
      some. The data, which revealed that fewer than one in six adults and only one in
      three seniors has proficient health literacy--defined as an ability to
      understand, read, interpret, and then act on health care information--shed new
      light on health literacy as a significant operational issue for health care,
      business, and health plan executives.

PMID- 17175737
TI  - High standards. A decade after the law went into effect, there is still debate
      about the pros and cons of the HIPAA privacy and electronic transaction
      regulations.
AB  - When congress passed the Health Insurance Portability and Accountability act in
      1996, the goal was to create a simpler, more standardized system that would
      eventually lower health care costs; reduce errors through safe, universally
      accepted electronic communication of health care transactions; and eliminate
      paper claims. Ten years later, the jury is still out on whether HIPAA has been
      worth the time, energy, and financial investment for insurers. That's not to say,
      however, that HIPAA hasn't generated benefits while also creating new challenges.
      "Standards made sense," says Tom Fitzpatrick, Horizon Blue Cross Blue Shield of
      New Jersey's director of enterprise strategic planning, "but no one ever said it
      would be fast, cheap, or easy. It was challenging to integrate proprietary claims
      systems and legacy software with the new standards that took effect in October
      2003. But that wasn't the end of the story. HIPAA's privacy and security rules
      and the standard identifiers have meant even more upgrades and improvements and
      have required payers to spend millions of additional dollars over the past three
      years on HIPAA compliance." According to a set of quarterly surveys conducted by
      HIMSS/Phoenix Health Systems, progress has actually been fairly rapid. On the
      other hand, some things have remained much the same. In 2003, payers cited
      "understanding/interpreting the legal requirements" as the most difficult aspect
      of the HIPAA remediation process, followed by "achieving successful integration
      of new policies and procedures" and "resolving issues with third parties". In
      2006, the barriers are similar, with users citing the same top two struggles.

PMID- 17175738
TI  - The duck heard 'round the world.

PMID- 17175739
TI  - Reaching out to retirees.
AB  - The numbers pertaining to the approaching demographic boom in health-care-related
      expenditures are eye-popping: Health-related financial products to help retiring
      baby boomers deal with out-of-pocket costs alone will generate up to 80 billion
      dollars in revenues and 8-12 billion dollars in pre-tax profits by 2014. But
      health insurers will have to refocus their efforts if they want to take full
      advantage of this opportunity. (For more, see "Turning Subscribers Into
      Customers: The Future Is Now" in the July/August issue, the first in this two
      part series.) Two areas are critical: product innovation to provide comprehensive
      solutions that meet seniors' needs more effectively, and advice-based
      distribution that creates privileged customer relationships.

PMID- 17175741
TI  - Medical underwriting gets an electronic makeover.
AB  - Taditional new business underwriting, especially in small group and individual
      markets, is limited by the amount of information that carriers obtain. The
      current method of medical underwriting driven by questionnaire responses is labor
      intensive and time-consuming for the prospective insured, the broker, and the
      insurance carrier.

PMID- 17175740
TI  - Fed up with fraud.
AB  - The national cost of health care reached 1.9 trillion dollars in 2004, or 6280
      dollars for every man, woman, and child in the United States. And, although they
      are the exception rather than the norm, individuals intent on committing fraud
      and abuse are not far behind. According to the Centers for Medicare & Medicaid
      Services, the estimated annual loss to the government and health insurers from
      fraud continues to exceed 100 billion dollars. In a recent semiannual report to
      Congress, the Department of Health and Human Services (HHS) Office of Inspector
      General announced expected recoveries of 1.02 billion dollars for the first half
      of fiscal year 2006. At this rate, less than 5 percent of the losses from fraud
      and abuse are recovered annually.

PMID- 17175742
TI  - Service oriented architecture: adding value to legacy IT systems.

PMID- 17175743
TI  - Management of early-stage lung cancer: past, present, and future adjuvant trials.
AB  - The standard of care with regard to adjuvant chemotherapy of lung cancer has
      changed remarkably over the past 3 years. Until the initial report of the
      International Adjuvant Lung Trial in 2003, there was no real evidence from any
      individual randomized clinical trial (RCT) that adjuvant chemotherapy improves
      survival in resectable non-small-cell lung cancer. However, five RCTs that have
      now been reported indicate that adjuvant chemotherapy is effective, at least in
      certain subgroups of resectable patients. Moreover, numerous meta-analyses have
      also reported a positive effect from adjuvant treatment. Nonetheless, because of
      methodologic. issues and conflicting results, the question of who should be
      treated and what constitutes optimal adjuvant therapy remains controversial. This
      article reviews the recent randomized trials that have contributed to a change in
      the state of the art, as well as some of the methodologic problems that may have
      confounded their proper interpretation. It also considers newer approaches to
      adjuvant therapy, with a particular focus on strategies that incorporate our
      growing knowledge of molecular medicine and predictive factors to the field of
      adjuvant chemotherapy of lung cancer.

PMID- 17175744
TI  - Managing acute myeloid leukemia in the elderly.
AB  - Acute myeloid leukemia (AML) is a disease of the elderly, with the majority of
      patients diagnosed in their 6th and 7th decade of life. Older patients with AML
      are less likely to achieve complete remission after induction chemotherapy, and
      they suffer from higher rates of leukemia relapse compared to younger cohorts.
      Suboptimal outcomes are the result of adverse biologic characteristics of
      leukemia in the elderly, as well as the presence of medical comorbidities and
      patient or physician preferences as to initiating treatment. In addition, there
      is a distinct lack of randomized, prospective data to guide management decisions
      for the treatment of AML in the elderly. Patients who are over age 75, with poor
      performance status, multiple comorbidities, or poor prognostic features, should
      be considered for a clinical trial or palliative therapy. Elderly patients who
      are candidates for standard induction chemotherapy and achieve complete remission
      are unlikely to benefit from intensive postremission therapy and should be
      referred to a clinical trial when possible. Further prospective trials are needed
      to identify a tolerable, effective treatment regimen for older patients with AML.

PMID- 17175745
TI  - Progress with a purpose: eliminating suffering and death due to cancer.

PMID- 17175746
TI  - Does this woman have gestational trophoblastic disease?

PMID- 17175747
TI  - Prevention of colorectal cancer: an emerging role for high-dose vitamin D
      supplementation?

PMID- 17175748
TI  - Teleoncology extends access to quality cancer care.

PMID- 17175749
TI  - Making the case for NIH funding: how cures are built on decades of research.

PMID- 17175750
TI  - Schmidt-Nielsen Mentor Award. From mentee to mentor: lessons learned along the
      way.

PMID- 17175751
TI  - [Health services research: innovation transfer in clinical research].
AB  - Clinical research in Germany suffers from a structural crisis caused by
      inappropriate input, suboptimal output and low efficiency. The situation is
      aggravated by fixed DRG-based payments, fix charges for education and research
      and reductions in governmental funding. Both healthcare system and clinical
      research in Germany are characterized by a profound sectorization, followed by
      resource competition between basic science and patient-oriented research. Basic
      biomedical research in Germany is widely accepted in the international context,
      but there is a lack of research on the transfer of basic science to clinical
      trials and everyday healthcare. According to international examples, the 1999
      systematology of the Deutsche Forschungs-Gemeinschaft (DFG), a German research
      foundation, has to be expanded to the dimension of innovation transfer. Clinical
      translational research focuses on the transfer of basic science to clinical
      trials, and outcomes research, also known as health services research, describes
      the transfer of results from clinical trials (efficacy) to clinical application
      (effectiveness). Outcomes research is interdisciplinary, multiprofessional and
      patient-oriented. The so-called effectiveness gap between efficacy and
      effectiveness is determined by patient-sided, professional, organizational and
      system factors. Outcomes research provides university-based medical research
      centers with the opportunity to join other stakeholders of the healthcare system
      and to integrate the universities' scientific standard with its own further
      development. It is suggested that this widened perspective plays a key role in
      settling the crisis of clinical research in Germany.

PMID- 17175752
TI  - [Opinion: prevention and health services research from the point of view of the
      German Forum on Disease Prevention and Health Promotion].
AB  - The article presents the point of view of the German Forum on Disease Prevention
      and Health Promotion that health promotion and prevention and health care
      research are not only similar as to their self-concept, structure and future
      tasks, but that health promotion and prevention need the systematic support of
      health care research to improve its policy impact. Furthermore, the article
      informs about the latest developments and the current state of disease prevention
      in Germany, presents a survey of the structure and work of the German Forum on
      Disease Prevention and Health Promotion and lists desirable topics for future
      studies in the field of health services research.

PMID- 17175753
TI  - [How to change physicians' practice--health services research with the knowledge
      performance gap on focus].
AB  - How can the knowledge-performance gap be bridged? The discrepancy between our
      scientific knowledge on the one hand and its inadequate application in everyday
      practice on the other remains a major challenge for implementation research.
      Looking back on ten years of Health Services Research and acknowledging the
      achievements of educational research we have gained access to a variety of
      research findings and tools describing how physicians'--and other health
      professionals'--behavior and performance in medical care may be influenced. The
      time has come for testing and evaluating them.

PMID- 17175754
TI  - [Health services research--from the Health Research Council's perspective].
AB  - As early as 1994, the Health Research Council of the Federal Ministry of
      Education and Research started activities to outline a strategic concept for
      health services research in Germany. The Health Research Council set the stage
      for the initiation of a common funding program on health services research of the
      statutory health insurance funds, the Federal Ministry for Education and Research
      and the Federal Ministry of Health. This funding program has provided an
      important stimulus to health services research in Germany. Moreover, it has
      promoted the involvement and responsibility of the statutory health insurance
      funds in health services research. In future the funding program will be
      continued and additionally involve pension insurance funds as well as private
      health insurance funds. In addition to this special funding program there is a
      need for a coordinated approach to the further development of health services
      research in Germany--a common task for both research and funding organizations in
      health research.

PMID- 17175755
TI  - [Health services research and guidelines--from the Association of the Scientific
      Medical Societies' (AWMF) perspective].
AB  - The Association of the Scientific Medical Societies (AWMF, Arbeitsgemeinschaft
      der Wissenschaftlichen Medizinischen Fachgesellschaften) is an umbrella
      organization. It currently represents 151 scientific societies and thus the
      majority of medical researchers in Germany. Through the coordination and support
      of the scientific medical societies, the AWMF significantly contributes to health
      services research by establishing guidelines that ensure a high quality of
      healthcare. To this purpose, AWMF founded a guideline committee in 1995, whose
      objective is to assist AWMF member societies in the establishment of guidelines,
      the organization of training sessions for AWMF guideline representatives, the
      hosting of regular guideline conferences and the close cooperation with the
      German Medical Association (Bundesarztekammer, BAK) and the National Association
      of Statutory Health Insurance Physicians (Kassenarztliche Bundesvereinigung, KBV)
      in the development of national disease management guidelines (Nationale
      Versorgungs Leitlinien, NVL). Together with the Agency for Quality in Medicine
      [AQuMed; Arztliches Zentrum fur Qualitat in der Medizin (AZQ)], AWMF published a
      'German Instrument for Methodological Guideline Appraisal' ('Deutsches Instrument
      zur methodischen Leitlinien-Bewertung', DELBI) in order to assure the quality of
      the guideline development process. A close cooperation has also developed between
      AWMF and the German Medical Association within the scope of their program for
      promoting health services research and with the Board of the German Network for
      Health Services Research (Deutsches Netzwerk for Versorgungsforschung, DNVF).
      Furthermore, AMWF has acknowledged a special need for improving the financial and
      conceptual promotion of a systematic evaluation of guideline development and the
      implementation and application of guidelines in everyday clinical practice.

PMID- 17175756
TI  - [Strengthening health services research: the development of the "German Network
      for Health Services Research" (DNVF)].
AB  - One of the main challenges in health services research is to overcome the
      structural and professional boundaries restricting the opportunities for
      cooperation between researchers, clinicians, and practitioners in designing and
      conducting applied research. In our view, two steps are necessary to strengthen
      linkage and exchange between organizations and bodies interested in health
      services research. First, reconnecting the different scientific disciplines and
      researchers working in the field of health services research is essential.
      Second, it is necessary to bring both researchers and the users and funders of
      research together in order to ensure that the research agenda is pursuing the
      right questions and to foster the translation of the data generated into valuable
      information for practical decisions. The "German Network for Health Services
      Research" was launched on May 2, 2006, by 26 representatives of different
      national medical and public health associations. The aim of this network is to
      help bridge the gap between the scientific communities on the one hand and
      between researchers and practitioners on the other hand.

PMID- 17175757
TI  - [High utilization of health insurance services by the elderly--analysis of
      hospital and drug utilization data].
AB  - The present contribution discusses the utilization of the healthcare system by
      elderly patients in Germany. First, the paper focuses on the detailed
      characterization of a group of people aged 60 years or more (N = 73,454). Second,
      the objective is to analyze the data for high utilization of healthcare services
      by older men and women. The analysis is based on data regularly recorded by a
      German health insurance agency for the year 2000. High utilization is
      operationalized by a 10% cutoff for users with the highest number of treatments,
      highest costs and/or other criteria depending on the respective health service
      sector. The insured group investigated received approximately 1.4 million
      prescriptions, producing costs of 42 million E. High utilizers account for 32% of
      all prescriptions and 44% of the costs, respectively. At the same time, the age
      groups with the highest prescription rates do not cause the highest costs: So the
      relationship between age and prescription drug expenses as well as between age
      and prescription rates does not display an arithmetically increasing pattern.
      Within the timeframe investigated 26,000 hospital treatments were accounted for
      by 21.75% of the elderly under research. In total, they caused expenses of 88
      million E. High utilization in the hospital sector was operationalized by four
      criteria. Sex- and age-specific analysis of high utilization of hospital
      treatment revealed that the four different criteria apply to different insured
      groups. In summary, the high utilization of healthcare services appears to be a
      multidimensional phenomenon.

PMID- 17175758
TI  - [Multiplicity in randomized trials I: Endpoints and treatments].

PMID- 17175759
TI  - New push for PBC.

PMID- 17175760
TI  - "Sloppy short-term thinking is passing for strategy in the NHS".

PMID- 17175762
TI  - Dying for a nurse. Interview by Emma Vere-Jones.

PMID- 17175761
TI  - "We need to be savvy in computer literacy and in managing information".

PMID- 17175763
TI  - Innovation that is saving lives. Interview by Victoria Hoban.

PMID- 17175765
TI  - Muscle physiology. Part 3: Muscles--the working units.

PMID- 17175764
TI  - Risks posed by mystery illness.
AB  - Patients may present with unknown illness caused by accidental or deliberate
      release of biological, chemical or radioactive material or a new/emerging
      disease. Nurses must be aware of the protocols to follow to ensure their own
      safety and that of other patients. This article discusses the national advice in
      dealing with incidents or outbreaks of unusual illness.

PMID- 17175766
TI  - Nurses' role in nutritional assessment and screening: Part one of a two-part
      series.
AB  - This article (part one of two) explores the importance of nutritional assessment
      and the basic tools for identifying those at risk of malnutrition.

PMID- 17175767
TI  - "Nursing must have a voice in political debate".

PMID- 17175768
TI  - The organisation of the RAMC during the Great War.
AB  - INTRODUCTION: At the 90 year anniversary of the Battle of the Somme, it is
      important to remember the members of the RAMC who served in the Great War,
      especially the more than one thousand Medical Officers who gave their lives.
      LEADERSHIP: The RAMC during the First World War was a Corps led by some able
      officers such as Sir Arthur Sloggett in France and Sir Alfred Keogh in London.
      Sir Douglas Haig was in overall command, his leadership style impacting on the
      RAMC. RECRUITMENT OF MOS: There were problems in filling the ranks of the Corps,
      both before the conflict, as well as well as during the War, and a significant
      number of civilian medical practitioners were recruited to the RAMC. Shortages
      were only really addressed when the Americans joined the conflict. TRAINING OF
      CIVILIAN MOS: The great need for MOs meant that there was little time for formal
      training of civilian MOs and many felt unsuited for war work. This was recognised
      by the authorities, who gradually set up centres of instruction. WORK OF RMOS:
      The workhorse of the organisation was the Regimental Medical Officer, who had an
      important role in disease prevention and the conservation of manpower, in a type
      of conflict (trench) that required a ready supply of personnel. Although an
      important role, some doctors found the job frustrating. CASUALTY EVACUATION:
      During the War, the RAMC managed to improvise an efficient system for handling
      casualties, the aim to give speedy treatment and to return the men to the front
      in the shortest possible time. CONCLUSIONS: The RAMC during the GreatWar was a
      highly structured and efficient organisation, geared towards maximising its
      available manpower, important in trench warfare.

PMID- 17175769
TI  - The house advancement anoplasty for treatment of anal disorders.
AB  - OBJECTIVES: Anal advancement flaps treat a variety of anal disorders. In recent
      years the "House" advancement flap has been used with good success, the term
      referring to the shape of the flap used. It is simple with few shortcomings. We
      reviewed a single centre's experience of this procedure. METHODS: All patients
      who underwent a house advancement flap between 1996 and 2001 were identified. The
      case notes were examined and data collected on indication for surgery,
      complications, follow-up and outcome. RESULTS: Thirteen consecutive patients were
      identified, mean age of 44 years. Indications for surgery were chronic anal
      fissure, fistulous disease and post surgical deformity or stenosis of the anal
      canal. Median follow-up was 37 months (25-84). In 9 patients the flaps healed
      within 4 weeks. In the remaining 4 patients the flaps healed by secondary
      intention over a median of 14 weeks (8-20). Postoperative complications occurred
      in 5 patients (3 donor site separation and 2 flap retraction). Two patients
      developed recurrence of their original disorder. Eleven patients have relief of
      pre-operative symptoms with fully healed flaps. CONCLUSION: This procedure is
      simple, easy to construct and robust. It can be performed for a variety of anal
      disorders with satisfactory results and few complications and should be in every
      Coloproctologist's armamentarium.

PMID- 17175770
TI  - A fellowship in craniofacial surgery.

PMID- 17175771
TI  - Psychological morbidity during the 2002 deployment to Afghanistan.
AB  - Questionnaires were completed by military personnel on arrival (n=1,696) in
      Kabul, Afghanistan and then again on departure (n=1,134). Analysis of the 113
      personnel who completed both the arrivals and departures questionnaire revealed a
      lower alcohol use score after deployment (AUDIT mean difference (post-deployment 
      pre-deployment) = -0.39, 95% confidence interval (CI) = - 1.25 - +0.47) and no
      significant change to mental health (GHQ mean difference = 0.55, 95% CI = -0.07 -
      +1.17). An increase in psychosomatic symptoms (GHQ A mean difference = 0.22, 95%
      CI = -0.03 - +0.47) is considered to result from the adverse conditions, but it
      is not supported by other mental ill health markers. In conclusion, there
      appeared to be no negative effect on mental health from deployment to
      Afghanistan.

PMID- 17175772
TI  - The madness at Deolali.

PMID- 17175773
TI  - Ballistic fractures during the 2003 Gulf conflict--early prognosis and high
      complication rate.
AB  - BACKGROUND: Ballistic fractures are devastating injuries often necessitating
      extensive reconstructive surgery or amputation, particularly if associated with
      high-energy transfer wounds. Infective complications are common, particularly in
      the austere environment encountered in war. We present the management and early
      outcome of these injuries with reference to the mechanism of injury and bony
      injury. METHOD: Data on ballistic fractures was collected prospectively during
      the 'war-fighting' phase of the 2003 Gulf Conflict, between 19th March and 20th
      May. Fractures were scored using the Red Cross Fracture classification and early
      outcome analysed. RESULTS: Thirty-nine patients, with 50 ballistic fractures,
      were treated by British military surgeons. Patients were predominantly Iraqi
      (90%) and 50 per cent of ballistic fractures were caused by bullets. Seventeen
      upper limb fractures and 33 lower limb fractures were sustained. There were seven
      traumatic amputations, and a further 2 limbs were amputated primarily. Methods of
      primary stabilisation for the remaining 41 fractures were: external fixation
      (22%), POP (14.5%), K-wires (14.5%) traction (10%), and no stabilisation (39%).
      Seven individuals were evacuated early after primary surgery, hence 43 ballistic
      fractures were available for follow-up. 13/43 (30%) of wounds became infected,
      5/43 (11.5%) were deep infections necessitating surgical drainage. There were 4
      late amputations (9.5%), 3 of which had initially been managed by external
      fixation. Infection occurred significantly more often in gunshot fractures
      (10/21, 48%), wounds closed primarily against the principles of war surgery (415,
      80%) and intra-articular fractures (3/3, 100%) (p=0.022, 0.024 and 0.023
      respectively). Differing methods of stabilisation had no bearing on the rate of
      postoperative infection. CONCLUSION: Ballistic fractures remain a challenge for
      trauma surgeons in times of war and still have a poor prognosis. Further work is
      required to determine the optimal treatment of these injuries during conflicts.
      In addition, there still seems to be a continued need to re-learn the principles
      of war surgery in order to minimise complications and optimise functional
      recovery.

PMID- 17175774
TI  - An unusual case of talonavicular dislocation with associated ipsilateral foot
      fractures.
AB  - We describe a previously unreported form of a talonavicular dislocation
      complicated by navicular, talar neck and open calcaneal fractures. Prompt
      recognition and rapid reduction of fractures and dislocations gives the best
      possible outcome. The presence of serious distracting injuries can alter
      priorities, however the "lesser" injuries often lead to long term morbidity after
      recovery from the life-threatening injuries.

PMID- 17175775
TI  - Military psychiatry.

PMID- 17175776
TI  - Ernst Von Bergmann.

PMID- 17175778
TI  - Rethinking regulation: is one large body the answer?

PMID- 17175779
TI  - Proving the point. Interview by Adele Waters.
AB  - NHS cutbacks mean it is even more important to evaluate the relationship between
      staffing levels and patient outcomes.

PMID- 17175780
TI  - Tender, loving care.
AB  - Early diagnosis and treatment of retinopathy can save premature babies' sight. In
      one neonatal clinic, nurses are at the forefront of providing a service which
      reflects the unit's caring ethos.

PMID- 17175781
TI  - Retail therapy is a risky treatment.

PMID- 17175782
TI  - Providing patient-centred care in an intensive care unit.
AB  - This article examines the provision of patient-centred care in an intensive care
      unit where patients' autonomy may be compromised. It discusses the Synergy Model
      as a framework for encouraging nurses to transform a technical and potentially
      dehumanising environment into a humane and healing place.

PMID- 17175783
TI  - Violence, aggression and physical assault in healthcare settings.
AB  - All healthcare professionals are at risk from violent and aggressive patients,
      however, it has been found that nurses are at particular risk. The actual
      incidence is difficult to determine because the definition of what constitutes a
      physical assault or a violent event is vague. This article considers how the
      terms violence, aggression and physical assault are conceptualised in the
      healthcare setting and suggests that nursing staff need to identify and act on
      any incident that compromises their personal safety.

PMID- 17175784
TI  - Tissue viability: understanding the mechanisms of injury and repair.
AB  - This article provides an overview of the pathophysiological processes that relate
      to tissue viability. Processes such as cellular damage, oedema and the
      inflammatory response are also discussed. Nursing management and the role of
      tissue viability nurses are briefly examined.

PMID- 17175785
TI  - Tissue donation.

PMID- 17175786
TI  - It will go swimmingly.

PMID- 17175787
TI  - Model for delivery.

PMID- 17175788
TI  - First-hand knowledge.

PMID- 17175789
TI  - [Diagnostic utility of macrophages in interstitial lung disease].

PMID- 17175790
TI  - [Teratoma of umbilical cord: a case report and literature review].
AB  - Teratomas are tumors that arise from totipotent embryonic germ cells. The
      umbilical cord is an extremely rare site for this tumor, only 12 cases have been
      reported in the medical literature. Herein we describe an umbilical cord mass
      presenting necrosis with clinical and histopathological features that can be
      considered as another case of umbilical cord teratoma. We discuss the
      differential diagnosis and review the complete literature on this subject.

PMID- 17175791
TI  - Neurocysticercosis: surgical treatment of an autochthonous case in a non-endemic
      region.
AB  - OBJECTIVE AND IMPORTANCE: This study describes a case of autochthonous
      neurocysticercosis in a non endemic region where a differential diagnosis with
      more frequent single parenchymal lesions must be carried out. CLINICAL
      PRESENTATION: The patient presenting generalized seizures and coma status under
      the suspicion of cerebral neoplasia was admitted to the neurosurgery division.
      MRI showed the presence of an ovoidal cystic lesion in right-frontotemporal
      region. INTERVENTION: After right fronto-temporal osteoplastic bone flap
      elevation and usual dural tacking and opening, trans-scissural subaracnoid access
      was made possible by microsurgical strumentation in right Sylvian fissure. A
      cystic, translucid lesion was identified in the deep Sylvian fissure, involving
      the distal segment of the fissure and the frontal lobe, the cystic lesion was
      removed surgically. Pathological examination showed a typical picture of
      neurocysticercosis. CONCLUSIONS: After both surgical and chemotherapeutic
      treatment with albendazole the outcome was successful. The diagnosis of
      neurocysticercosis should be taken into account in the presence of generalized
      seizures possibly due to single parenchymal lesions, even in non-endemic regions
      for this parasitic infection.

PMID- 17175792
TI  - [Primary cardiac echinococcosis].
AB  - Cardiac echinococcosis is very rare, even in endemic regions. It has been
      reported that cardiac involvement is seen in about 0.5-3% of human echinococcosis
      cases. A case of cardiac isolated hydatid desease that caused sporadic syncopal
      episodes is illustrated.

PMID- 17175793
TI  - [Retroperitoneal extraskeletal myxoid chondrosarcoma].
AB  - INTRODUCTION: Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumor
      included by WHO in the group of tumors of uncertain differentiation because well
      formed cartilage is rarely seen in its setting; moreover some of the
      immunophenotype features of the tumor are still controversial. The reciprocal
      translocation t(9;22)(q22;q12) has recently been identified in many cases, and
      this chromosomal aberration is currently considered high specific of this tumor.
      CASE REPORT: We report the case of a 75-year-old female submitted to radical
      nephrectomy for a voluminous kidney tumor with radiological evidence of
      extrarenal extension. RESULTS: Grossly the lesion was set in the perirenal fat
      tissue. Histological examination revealed a malignant mesenchimal tumor with
      myxoid f eatures and areas of chondroid differentiation consistent with the
      diagnosis of extraskeletal myxoid chondrosarcoma. According with the diagnosis
      the tumor showed focal positivity to NSE by immunohistochemistry. DISCUSSION:
      Differentiated cartilage is seen in extraskeletal myxoid chondrosarcoma in about
      30% of the cases. Our case is then interesting not only for the rare site of
      tumor location but also for the extension of chondroid differentiation areas
      found on histologic examination in the tumor setting. Moreover
      immunohistochemistry showed focal positivity of the neoplastic cells for NSE,
      according with recent studies demonstrating expression of some
      neural/neuroendocrine markers in extrascheletal myxoid chondrosarcoma.

PMID- 17175794
TI  - Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic
      soft tissue: new entities and new variants of old entities recorded during the
      last 25 years. Part XII: appendix.
AB  - In an eleven part series published in Pathologica, we have presented various
      tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic
      soft tissue (ST), which emerged as new entities or as variants of established
      entities during the last quarter of a century. Detailed clinicomorphological and
      differential diagnostic features of approximately sixty entities were chosen on
      the basis of their clinical significance and morphologic distinctiveness. The
      series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor,
      high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory
      myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic
      neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory
      myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g.,
      chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma),
      epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid
      liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal
      chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors
      (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma
      group), extranodal dendritic or histiocytic proliferative processes (follicular
      dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform
      xanthomatous tumor), and tumors with myoepithelial differentiation. The section
      devoted to selected pseudotumoral entities considered representatives of the
      hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma,
      rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic
      fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative
      parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors
      of digits) and infections (bacillary angiomatosis), and normal organs (glomus
      coccygeum). To conclude the descriptive phase, supplementary material has now
      been collected and appended in an attempt to provide a quick digest of essential
      knowledge both for comparison and differential diagnosis. The data have been
      tailored to synthesize diverse sources, integrating clinical elements and
      references to articles that previously appeared in Part I ("Introduction"), Part
      II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At
      the very least we hope this final part ("Appendix") will provide the reader with
      a useful tabular organization of ST lesions and a reference resource.

PMID- 17175795
TI  - [Comparative anatomy of the hand].
AB  - The pentadactyl scheme is common to all tetrapods, even in case of adaptative
      phenomenon (five digits are observed during ontogenesis), or in case of
      functional convergence The carpal organization with two rows is common too, if we
      take into account the desappearing of the central bones in mature man. The sellar
      shape of the trapeziometacarpal joint of the thumb, to often attributed to Man
      and his only thumb, is in fact the regular shape of all carpometacarpal
      articulations and present in very ancient primitive primate fossils. Some
      discontinuous caracters in Man (entepicondylar tunnel) are present in all
      individuals of some species (carnivors). Rarely present in Man, it can
      exceptionally produce a real pathology.

PMID- 17175796
TI  - [Pain perioperative in surgery of the hand].
AB  - Pain has to be treated during the perioperative period. The recent improvement in
      pain treatment results from a better understanding of pain mechanisms, strict
      evaluations and appropriate protocols for pain management. Mainly nociceptive,
      postoperative pain looks more and more like neuropathic pain when it persists or
      increases. Therefore, analgesics are no more effective and antihyperalgesiant
      drugs must use. Preventive treatments have to be considered first as the best
      pain treatment. Basically, perioperative pain has to be understood as a standard
      quality management by the medical and surgical team.

PMID- 17175797
TI  - [The treatment of digital nerve defects by the technique of vein conduit with
      nerve segment. A randomized prospective study].
AB  - OBJECTIVE: This study aims to compare the results of treating digital nerve
      defects with autologous sural nerve grafts as compared to using a vein conduit
      with interposition of a posterior interosseous nerve segment. METHODS: This study
      is a clinical, prospective, randomized and blinded trial, comparing digital nerve
      defects treated by two different surgical techniques. It included a total of 50
      digital nerves (25 patients in each treatment group), with a mean follow up of
      10.2 (SD 1.4) months. In addition, the impact of five different factors (type of
      surgery, size of nerve defect, patient's age, type of lesion and lesion age) on
      the final outcome were evaluated. RESULTS: In respect of the sensory assessment,
      the static two point discrimination score was 6 mm for both groups . According to
      the Al-Ghazal Scoring Method, the autolougus sural nerve graft group scored a
      mean (sd) of 7.7 (1.9) points, while vein conduit with interposition of a
      posterior interosseous nerve segment group scored 6.9 (2.1). Under multivariate
      analysis, both patient's age and lesion age proved to be important independent
      factors, having influenced almost all results. The group treated with vein
      conduit with interposition of a posterior interosseous nerve segments showed
      fewer complications than the group treated using sural nerve. CONCLUSION: Based
      on the results obtained, we concluded that the sensory scores were equal in both
      groups. We also concluded that the vein conduit and posterior interosseous nerve
      graft procedure offered some advantages in terms of the complication rate.

PMID- 17175798
TI  - [Schwannomas of the peripheral nerve in the hand and the upper limb: Analysis of
      14 cases].
AB  - The Schwannomas are usually considered as enucleable lesions of which the
      excision under microscope doesn't entail a post-operative deficit. Having
      frequently observed the inclusion of fascicle in the tumor, we wanted to verify
      the absence of deficit in a retrospective survey. Our survey is composed of 14
      patients operated of schwannoma of the superior member and whose mean age is 53
      years old. All patients presented an average of nine months old palpable mass;
      the pain was present in four cases; paresthesiae in seven cases; irritatif
      syndrome in ten cases. A preoperative sensory deficit was present in two patients
      but without any case of preoperative motor deficit. The schwannoma was localized
      in eight cases in the hand, one case in the forearm, two cases in the elbow, two
      cases in the arm and one case in the armpit. The affected nerves were the digital
      ones in six cases, the main trunk of the median nerve in four cases, the trunk of
      the ulnaire nerve in three cases and the sensory branch of the radial nerve in
      one case. All tumors have been operated under a microscope. The enucleation was
      possible without fascicle lesion in six cases. In the eight other cases we have
      proceeded to a resection of indissociable fascicles. The diagnosis is confirmed
      by the histologycal examination in all cases. In postoperative, the two patients
      that presented a preoperative sensory deficit no longer presented it. On the
      contrary, three patients that didn't have any preoperative deficit presented each
      a post-operative sensory deficit with in addition a motor trouble in one of
      cases. We conclude from this survey that there is a risk of peroperative fascicle
      lesion even when using the microscope. This information is important to consider
      in the setting of deciding how to proceed before the excision of this benign
      lesion.

PMID- 17175799
TI  - [The step-cut shortening osteotomy of the shaft of the ulna, technique and
      results].
AB  - Step-cut shortening osteotomy of the ulna for impingment of the distal ulna
      relies on the principles enunciated by Desanfans 1953. We recommend the plate be
      placed on either the palmar or the dorsal aspect of the ulna. Used since 1990
      this technique has enabled primarily bony healing by 6 months in all the 18 cases
      operated upon. A significant clinical improvement as measured by the scoring
      system of Chun and Palmer was noted at a median follow-up of 95.7 months.
      Shortening did not unfortunately, appear to stabilize the distal ulna and those
      patients with residual clinical radioulnar instability had significantly worse
      results. We conclude that the technique presented gives reliable bone healing. It
      is a versatile and simple technique that requires no special instrumentation but
      does demand skill and precision.

PMID- 17175800
TI  - Conservative treatment versus scaphotrapeziotrapezoid arthrodesis for Kienbock's
      disease. A retrospective study.
AB  - Efficiency of surgical treatment in Kienbock's disease has never been proven in
      the long term. We retrospectively reviewed the charts of the 104 patients treated
      by various techniques for Kienbock's disease from 1981 to 1999 in our unit. A
      comparison was made between 19 cases treated conservatively (amongst 59) and 11
      cases (amongst 25) treated by scaphotrapeziotrapezoid (STT) arthrodesis with a
      mean follow-up of 13 years. The two groups were statistically comparable in
      stage, age, sex ratio, number of manual workers. STT arthrodesis was responsible
      for an increased loss of mobility, an increase of barometric pain, a longer
      rehabilitation time and more fractures of lunatum than conservative treatment.
      Those results question about indications for STT in Kienbock's disease.

PMID- 17175802
TI  - [Boxer's fracture: Cost evaluation orthopaedic or surgical treatment].
AB  - Many methods of treatment have been proposed for fractures of the neck of the
      fifth metacarpal ranging from early mobilization to various surgical techniques.
      The aim of this retrospective study was to evaluate the functional results and
      the costs of closed as opposed to open treatment (Foucher's K-Wire technique).
      MATERIALS AND METHODS: We conducted a retrospective study on all fractures
      without rotational deformity and with a palmar angulation less than 40 degrees C.
      Details of the patients, the fractures, functional results and the cost of
      management were analyzed. RESULTS: The functional results were similar between
      the two groups, but surgical treatment increased the cost of treatment to 1100
      euros. CONCLUSIONS: We advocate the use of closed treatment for these fractures.
      The functional results are the same as with surgical management, but the costs
      are much reduced.

PMID- 17175801
TI  - [Arthroscopic treatment of dorsal ganglion cyst at the wrist. About 54 cases].
AB  - INTRODUCTION: Ganglion cyst of the wrist can, some time, need surgery. Different
      arthroscopic technical procedures have been described. We report our experience
      in all articular resection of dorsal ganglion cyst of the wrist. OBJECTIVES:
      Evaluation of efficiency of resection of dorsal ganglion cyst of the wrist by of
      arthroscopic resection of the pedicle. METHODS: Fifty-four cysts of 52 patients
      have been evaluated retrospectively. Operative data, pain, strength, recurrence
      and complications have been collected. RESULTS: Average follow up was 28 months
      (6 to 78). Return to work was 8,8 days, operative time 41 minutes (25 to 90). In
      67% cases, the operation was judged easy. Three surgeries had to be performed
      open. Complications were one hematoma and one neurodystrophy. Pain decrease from
      3,37 to 1,76 on analogical pain scale. Flexion was 89% of opposite side,
      extension 88%. Sixteen recurrences (29.7%) were found. Sixty percent of those
      recurrences occurred during the first year experience. But independently of
      experience, the operative performance was foun difficult in 1 time on 3.
      CONCLUSION: Endoarticular arthroscopic resection of the pedicle of ganglion cyst
      is not so reproducible. In experimented hands, it remains a difficult procedure
      after a long learning curve with a recurrence rate 3 times higher from what is
      reported in literature for open surgery. For our discharge, our long follow-up
      can contain some cases of de novo cyst explaining this high rate, the learning
      curve is certainly the main reason for our high recurrence.

PMID- 17175804
TI  - [Bilateral capitulum humeri fracture, a case report and review of the
      literature].
AB  - Fracture of the capitellum is an intra-articular fracture of the distal humeral
      metaphysis and usually occurs in the frontal plane. It is a rare fracture and
      even more unusual when bilateral. The authors report a case of bilateral isolated
      fracture of the capitellum (Hahn-Steinthal type I) in a woman aged 28 years,
      treated surgically. A posterolateral approach was used for both elbows. Internal
      fixation was performed using two Herbert screws in the right elbow, and AO screws
      in the left elbow. Both elbows were immobilised for 3 weeks before commencing an
      intensive mobilization program guided by a physiotherapist. The end result was
      very satisfactory: both elbows were pain-free, with a complete range of movement
      on the right and a 10 degrees loss of extension on the left. Radiologically,
      consolidation was complete and there were no signs of avascular necrosis. Based
      on a review of the literature, the authors favour the use of Herbert screws in
      the treatment of capitellar fractures. They give good inter-fragmentary
      compression and reduce the risk of damaging the articular surface due to their
      subarticular position.

PMID- 17175803
TI  - [Thenar lipoma causing nervous compression. A case report].
AB  - The authors report the case of a thenar lipoma in a 40-year-old women, associated
      with altered sensation in the territory of the adjacent digital nerves of the
      thumb and index. Magnetic resonance imaging proved useful in the establishment of
      the diagnosis and for pre-operative planning. Treatment consisted of excision of
      the tumor. At twelve months postoperatively, the patient had complete return of
      sensation and no sign of tumour recurrence.

PMID- 17175805
TI  - [Insulated arm pilomatrixoma: A rare localization. A case report].
AB  - Pilomatrixoma also known as calcified epithelioma of Malherbe, is a rare benign
      cutaneous tumor. It is most commonly seen in the head and neck areas, during the
      first two decades of life. We report a 30-year-old female patient with a rare
      localisation of pilomatrixoma in the right arm. The pilomatrixoma was excised and
      at one year follow-up there has been no evidence of recurrence.

PMID- 17175806
TI  - [Hibernoma of the forearm].
AB  - Hibernomas are rare benign tumours originating from the brown fat found in the
      foetus and animals that hibernate. In most cases they present as a slowly growing
      painful mass situated in those regions where this type of fat persists in the
      adult. We report a case of hibernoma of the forearm, which is an unusual
      localization, and we review the diagnostic and therapeutic aspects of this of
      tumour whose main differential diagnosis is liposarcoma.

PMID- 17175807
TI  - [Aneurismal bone cyst of clavicle: A case report].
AB  - Aneurismal bone cyst is a rare tumour. The authors report an exceptional case in
      its clavicle localization. They review the diagnosis circumstances and treatment
      modalities of this pathology. The occurrence of the cyst is linked to vascular
      homodynamic disturbance and its discovery in a post-traumatic context has been
      assessed by the histology exam. Although numerous therapeutic trials, radical
      removal versus conservatory methods avoid relapse. Finally, resection of the
      clavicle leading to few functional consequences should be recommended for the
      cure of evoluted aneurismal bone cyst.

PMID- 17175808
TI  - The role of GABA in the mediation and perception of pain.
AB  - A great deal of effort has been expended in attempting to define the role of GABA
      in mediating the transmission and perception of pain. Pursuit of this question
      has been stimulated by the fact that GABAergic neurons are widely distributed
      throughout the central nervous system, including regions of the spinal cord
      dorsal horn known to be important for transmitting pain impulses to the brain. In
      addition, GABA neurons and receptors are found in supraspinal sites known to
      coordinate the perception and response to painful stimuli and this
      neurotransmitter system has been shown to regulate control of sensory information
      processing in the spinal cord. The discovery that GABA receptor agonists display
      antinociceptive properties in a variety of animal models of pain has provided an
      impetus for developing such agents for this purpose. It has been shown that GABA
      receptor agonists, as well as inhibitors of GABA uptake or metabolism, are
      clinically effective in treating this symptom. However, even with an enhanced
      understanding of the relationship between GABAergic transmission and pain, it has
      proven difficult to exploit these findings in designing novel analgesics that can
      be employed for the routine management of pain. Work in this area has revealed a
      host of reasons why GABAergic drugs have, to date, been of limited utility in the
      management of pain. Chief among these are the side effects associated with such
      agents, in particular sedation. These limitations are likely due to the
      simultaneous activation of GABA receptors throughout the neuraxis, most of which
      are not involved in the transmission or perception of pain. This makes it
      difficult to fully exploit the antinociceptive properties of GABAergic drugs
      before untoward effects intervene. The discovery of molecularly and
      pharmacologically distinct GABAA receptors may open the way to developing subtype
      selective agents that target those receptors most intimately involved in the
      transmission and perception of pain. The more limited repertoire of GABAB
      receptor subunits makes it more difficult to develop subtype selective agents for
      this site. Nonetheless, a GABAB agonist, CGP 35024, has been identified that
      induces antinociceptive responses at doses well below those that cause sedation
      (Patel et al., 2001). It has also been reported that, unlike baclofen, tolerance
      to antinociceptive responses is not observed with CGP 44532, a more potent GABAB
      receptor agonist (Enna et al., 1998). While the reasons for these differences in
      responses to members of the same class remain unknown, these findings suggest it
      may be possible to design a GABAB agonist with a superior clinical profile than
      existing agents. Besides the challenges associated with identifying subtype
      selective GABAA and GABAB receptor agonists, the development of GABA analgesics
      has been hindered by the fact that the responsiveness of these receptor systems
      appear to vary with the type and duration of pain being treated and the mode of
      drug administration. Further studies are necessary to more precisely define the
      types of pain most amenable to treatment with GABAergic drugs. Inasmuch as the
      antinociceptive responses to these agents in laboratory animals are mediated, at
      least in part, through activation or inhibition of other neurotransmitter and
      neuromodulator systems, it is conceivable that GABA agonists will be most
      efficacious as analgesics when administered in combination with other agents. The
      results of anatomical, biochemical, molecular, and pharmacological studies
      support the notion that generalized activation of GABA receptor systems dampens
      the response to painful stimuli. The data leave little doubt that, under certain
      circumstances, stimulation of neuroanatomically discreet GABA receptor sites
      could be of benefit in the management of pain. Continued research in this area is
      warranted given the limited choices, and clinical difficulties, associated with
      conventional analgesics.

PMID- 17175809
TI  - Distribution of GABA receptors in the thalamus and their involvement in
      nociception.

PMID- 17175810
TI  - GABA(A) agonists and partial agonists: THIP (Gaboxadol) as a non-opioid analgesic
      and a novel type of hypnotic.

PMID- 17175811
TI  - Rat modeling for GABA defects in schizophrenia.

PMID- 17175812
TI  - Epigenetic targets in GABAergic neurons to treat schizophrenia.

PMID- 17175813
TI  - GABAergic malfunction in the limbic system resulting from an aboriginal genetic
      defect in voltage-gated Na+-channel SCN5A is proposed to give rise to
      susceptibility to schizophrenia.

PMID- 17175814
TI  - GABA(A) receptor mutations associated with generalized epilepsies.

PMID- 17175815
TI  - From gene to behavior and back again: new perspectives on GABAA receptor subunit
      selectivity of alcohol actions.
AB  - gamma-Aminobutyric acid A (GABA(A)) receptors are believed to mediate a number of
      alcohol's behavioral actions. Because the subunit composition of GABA(A)
      receptors determines receptor pharmacology, behavioral sensitivity to alcohol
      (ethanol) may depend on which subunits are present (or absent). A number of
      knockout and/or transgenic mouse models have been developed (alpha1, alpha2,
      alpha5, alpha6, beta2, beta3, gamma2S, gamma2L, delta) and tested for behavioral
      sensitivity to ethanol. Here we review the current GABA(A) receptor subunit
      knockout and transgenic literature for ethanol sensitivity, and integrate these
      results into those obtained using quantitative trait loci (QTL) analysis and gene
      expression assays. Converging evidence from these three approaches support the
      notion that different behavioral actions of ethanol are mediated by specific
      subunits, and suggest that new drugs that target specific GABA(A subunits may
      selectively alter some behavioral actions of ethanol without altering others.
      Current data sets provide stronge)st evidence for a role of alpha1 subunits in
      ethanol-induced loss of righting reflex and alpha5 subunits in ethanol-stimulated
      locomotion. Nevertheless, three-way validation is hampered by the incomplete
      behavioral characterization of many of the mutant mice, and additional subunits
      are likely to be linked to alcohol actions as behavioral testing progresses.

PMID- 17175816
TI  - A role for GABA in alcohol dependence.

PMID- 17175817
TI  - Structure, pharmacology, and function of GABAA receptor subtypes.

PMID- 17175818
TI  - Structure-activity relationship and pharmacology of gamma-aminobutyric acid
      (GABA) transport inhibitors.

PMID- 17175819
TI  - Modulation of ionotropic GABA receptors by natural products of plant origin.

PMID- 17175820
TI  - Attenuation of C-reactive protein increases after exodontia by tramadol and
      ibuprofen.
AB  - The anti-inflammatory effects of ibuprofen and tramadol were investigated by
      measuring C-reactive protein concentrations after removal of an impacted lower
      third molar. Forty-five American Society of Anesthesiologists Class I patients
      were randomly categorized into 3 equal groups according to postoperative
      analgesic medication. The first group received tramadol (100 mg every 8 hours),
      the second group received ibuprofen (400 mg every 8 hours), and the last group
      received half doses of both drugs in combination (50 mg tramadol every 8 hours
      and 200 mg ibuprofen every 8 hours). C-reactive protein was measured before
      surgery to exclude the presence of any preexisting inflammatory condition that
      might interfere with the study. C-reactive protein was also determined
      immediately after surgery and 72 hours postoperatively. At 72 hours, C-reactive
      protein had increased over postsurgery baseline by 123% in the tramadol group (P
      < .001), 84% in the ibuprofen group (P < .001), and only 37% in the combined
      analgesic group (P = .078). These results suggest that tramadol may produce supra
      additive anti-inflammatory effects with ibuprofen after third-molar extractions.

PMID- 17175821
TI  - A prospective study of 2 sedation regimens in children: chloral hydrate,
      meperidine, and hydroxyzine versus midazolam, meperidine, and hydroxyzine.
AB  - The aim of this study was to compare both the behavioral and physiological
      effects of 2 drug regimens in children: chloral hydrate (CH), meperidine (M), and
      hydroxyzine (H) (regimen A) versus midazolam (MZ), M, and H (regimen B). Patients
      between 24 and 54 months of age were examined by crossover study design. Behavior
      was analyzed objectively by the North Carolina Behavior Rating System and
      subjectively through an operator and monitor success scale. Physiological data
      were recorded every 5 minutes and at critical points throughout the appointment.
      Sixteen patients completed this study. No significant differences in behavior
      were noted by the North Carolina Behavior Rating System or the operator and
      monitor success scale. A quiet or annoyed behavior was observed 93% and 90% of
      the time for regimen A and regimen B, respectively. Using the operator and
      monitor success scale, 63% of regimen A and 56% of regimen B sedations were
      successful. No statistically significant differences were noted in any of the
      physiological parameters between the 2 regimens. Ten episodes of hemoglobin
      desaturation were detected with regimen A sedations. There were no differences
      between the sedative drug regimens CH/M/H and MZ/M/H for behavioral outcomes or
      physiological parameters.

PMID- 17175822
TI  - The role of temperature in the action of mepivacaine.
AB  - The role of temperature in the action of local anesthetics was studied in 20
      healthy young volunteers with plain 3% mepivacaine injected periapically twice in
      their maxillary first premolar, the first time with the solution at a temperature
      of 20 degrees C and the second time at 4 degrees C. The pulpal response was
      measured with a pulp tester every minute. The onset of pulp anesthesia was found
      to be of no statistical difference between 20 degrees C and 4 degrees C. On the
      other hand, mepivacaine at a temperature of 4 degrees C was found to have a
      statistically significant longer duration of action. Our conclusion is that the
      drop in temperature of mepivacaine from 20 degrees C to 4 degrees C provides a
      longer duration of pulpal anesthesia.

PMID- 17175823
TI  - Delirium during intravenous sedation with midazolam alone and with propofol in
      dental treatment.
AB  - A 62-year-old man visited our clinic for dental implantation under intravenous
      sedation. He demonstrated increased psychomotor activity and incomprehensible
      verbal contact during intravenous sedation. Although delirium caused by midazolam
      or propofol in different patients has been reported, the present case represents
      a delirium that developed from both drugs in the same patient, possibly because
      of the patient's smaller tolerance to midazolam and propofol.

PMID- 17175824
TI  - Essentials of local anesthetic pharmacology.
AB  - It is impossible to provide effective dental care without the use of local
      anesthetics. This drug class has an impressive history of safety and efficacy,
      but all local anesthetics have the potential to produce significant toxicity if
      used carelessly. The purpose of this review is to update the practitioner on
      issues regarding the basic pharmacology and clinical use of local anesthetic
      formulations.

PMID- 17175826
TI  - Nurse-led community approach to asthma management for children.

PMID- 17175827
TI  - A world of difference: Australian nurse volunteers.

PMID- 17175829
TI  - Nurse-led cardiac clinics for adults with coronary heart disease.

PMID- 17175828
TI  - Best evidence to improve patient care.

PMID- 17175830
TI  - A nurse-initiated ED X-ray program.

PMID- 17175831
TI  - Improving emergency mental health triage.

PMID- 17175832
TI  - Paediatric fever education for emergency nurses.

PMID- 17175833
TI  - Classifications used by Australian forensic odontologists in identification
      reports.
AB  - Forensic odontologists are repeatedly called upon to assist in the identification
      of deceased persons. A great deal of information is available in the literature
      as to how and why comparative dental investigation of identification is performed
      but there is little information on the descriptive terms used in reporting these
      identifications. A forensic odontology report sets out the findings of a
      comparison between antemortem and postmortem evidence and indicates the
      odontologist's opinion on the identification. This opinion needs to be defendable
      in a court of law. This paper investigates the classifications utilised in the
      six states and two territories of Australia and reflects on the differences.
      Three states of Australia use American Board of Forensic Odontology
      classifications, whilst the remaining regions use a modified format. Since there
      are no significant legal, cultural or religious differences, and similar
      practitioners and clients, variation between regions within Australia would seem
      hard to justify. National standard terminology should be encouraged.

PMID- 17175834
TI  - Component analysis of dental porcelain for assisting dental identification.
AB  - The fluorescence of porcelain crowns recovered from the mouth of an unknown
      murder victim, and several control porcelain samples, were examined by
      fluorescent examination lamps. The fluorescence from two of the control samples
      was quite similar to that from the porcelain crowns recovered from the victim. To
      increase the objectivity of the results by quantitative analysis, the composition
      of each porcelain crown and control sample was also evaluated by wave dispersion
      X-ray microanalyser. The elements detected from the porcelain crowns of the
      victim matched those of two of the porcelain samples. Later, the antemortem
      dental records and radiographs of the victim were obtained through a dentist, who
      had recognized the name of the porcelain manufacturer in a postmortem dental
      information request placed on the Japanese Dental Association web page. Although
      component analysis of dental porcelain may be an effective means of assisting
      dental identification, a more rapid and non-destructive analysis for detecting
      the elements is required. The energy dispersive X-ray fluorescence (EDXRF)
      spectrometer was used for a pilot study of identification of porcelain
      composition.

PMID- 17175835
TI  - The use of dental radiographs for identification of children with unrestored
      dentitions.
AB  - The success of dental identification is often dependent on the extent of previous
      dental care and the location of detailed dental records. However, several factors
      limit available comparable data among children. There are often no clinical
      indications for dental radiography before the age of five and many children and
      adolescents have no restorative care. This reduces the amount of individualizing
      information suitable for comparative identification. The aim of this study was to
      investigate matching of dental x-rays from children without fillings at different
      ages, and to see if radiographic expertise facilitated radiographic comparison.
      Five general dental practitioners (GDP) and five oral and maxillofacial
      radiologists (OMR) attempted to match bitewing examinations from 30 children. The
      results showed that dentists are likely to match bitewing radiographs in these
      conditions. This likelihood is further enhanced when oral and maxillofacial
      radiologists compare images. This suggests that manual comparison of bitewings
      from children allow sufficient concordant visible points for identification to
      occur.

PMID- 17175836
TI  - Craniofacial identification by computer-mediated superimposition.
AB  - Mass disasters are associated with a large number of fatalities, with victims
      being visually unidentifiable in most cases. Dental identification, although
      being an important and valuable identification method, is subject to the
      availability and quality of antemortem and postmortem dental records. This paper
      presents a simple-to-use method of human identification using an antemortem
      photograph showing anterior teeth with superimposition onto a postmortem image
      using specific features of Adobe Photoshop. We present cases and discuss the
      benefits and difficulties of this method.

PMID- 17175837
TI  - Clinical and histopathological examination of experimental bite marks in-vivo.
AB  - Under rigorously controlled laboratory conditions, mechanically induced simulated
      human bite marks were made on pig skin to enable the clinical and
      histopatholgical study of experimental bite marks in-vivo. A series of bite marks
      were created on the abdomen and thorax of live anaesthetized juvenile pigs at
      specific times just prior to and after death. Following the release of the biting
      force clinical observations of antemortem wounds revealed slow diminishment of
      the bite indentations presumably due to dermal elastic recovery. Minutes after
      euthanasia of the animals, the indentations of the teeth from the postmortem bite
      marks faded rapidly. After the biting process the animals were placed on either
      the right or left side and this side was maintained until necropsy to examine for
      dependant and non-dependent side differences. All bite mark injuries located on
      the non-dependent side revealed specific pattern characteristics. However, on the
      dependent side whether the bite mark was antemortem or postmortem in areas of
      livor mortis, no clear pattern was visible. Histologically, the observations for
      each bite mark specimen were categorised by the presence or absence of
      extravasated red blood cells in the fatty or muscle layers. The histopathological
      findings correlate with the clinical observations of antemortem and postmortem
      bite marks located on the non-dependent side in regard to muscular erythema and
      extravasated red blood cells. It is clinically difficult to comment on temporal
      relationship of a bite mark in relation to time of death in areas affected by
      blood-pooling seen on the dependent side. In these situations, histopathological
      studies could be a reliable alternative to provide information regarding
      antemortem or postmortem injuries.

PMID- 17175838
TI  - A pilot study to determine the effects of skin contact on two commonly used
      dental impression materials.
AB  - Impression materials used in the analysis of bite marks are required to maintain
      their stability and integrity for extended periods. It has been observed that
      certain impressions taken of skin lose their properties with time, becoming
      sticky and unusable as evidence. The objective of this study was to investigate
      the onset of "stickiness" in two commonly used dental impression materials when
      brought into contact with skin. The two materials tested were Impregum and
      President. They were syringed into glass rings positioned on the upper arms of 28
      volunteers. Changes in stickiness were monitored over a four-month period using a
      tensile testing machine. A metal plunger was lowered onto the impression material
      and then retracted measuring the adhesive force of the material to the lower
      surface of the plunger. Over the research period 17 of the 28 rings of Impregum
      became sticky and changed colour from purple to turquoise. The remaining 11
      Impregum samples, all the President samples and all control samples remained
      unchanged over the 120 day period. The results of this study show that certain
      factors present in or on skin are responsible for the loss of surface integrity
      of Impregum. The factors responsible for these changes have not been established.

PMID- 17175839
TI  - Serious crisis in the practice of international health by the World Health
      Organization: the Commission on Social Determinants of Health.
AB  - The Commission on Social Determinants of Health (CSDH) is the latest effort by
      the World Health Organization to improve health and narrow health inequalities
      through action on social determinants. The CSDH does not note that much work has
      already been done in this direction, does not make a sufficient attempt to
      analyze why earlier efforts failed to yield the desired results, and does not
      seem to have devised approaches to ensure that it will be more successful this
      time. The CSDH intends to complement the work of the earlier WHO Commission on
      Macroeconomics and Health, which has not had the desired impact, and it is
      unclear how the CSDH can complement work that suffers from such serious
      infirmities. Inadequacies of both commissions reflect a crisis in the practice of
      international health at the WHO, stemming from a combination of unsatisfactory
      administrative practices and lack of technical competence to provide insights
      into the problems afflicting the most needy countries. Often the WHO has ended up
      distorting the rudimentary health systems of the poor countries, by pressuring
      them into accepting health policies, plans, and programs that lack sound
      scientific bases. The WHO no longer seems to take into account historical and
      political factors when it sets out to improve the health situation in low-income
      countries--which is supposed to be the focus of the CSDH. An alternative approach
      is suggested.

PMID- 17175840
TI  - Social determinants of health: present status, unanswered questions, and future
      directions.
AB  - This article reviews the current status of theory and research concerning the
      social determinants of health. It provides an overview of current
      conceptualizations and evidence on the impact of various social determinants of
      health. The contributions of different disciplines--epidemiology, sociology,
      political economy, and the human rights perspective--to the field are
      acknowledged, but profound gaps persist in our understanding of the forces that
      drive the quality of various social determinants of health and why research is
      too infrequently translated into action. Many of these gaps in knowledge concern
      the political, economic, and social forces that make implementation of public
      policy agendas focused on strengthening the social determinants of health
      problematic. The author identifies the areas of inquiry needed to help translate
      knowledge into action.

PMID- 17175841
TI  - "Social capital," GNP per capita, relative income, and health: an ecological
      study of 23 countries.
AB  - The effects of social capital, income inequality, and absolute per capita income
      were investigated in an ecological analysis of 23 rich and poor countries. Trust
      was chosen as an indicator of social capital, and GNP (gross national product)
      per capita and Gini index measured absolute and relative income, respectively.
      These independent variables were analyzed in a linear regression model with the
      dependent variables adult mortality rate (25-64 years), life expectancy, and
      infant mortality rate (IMR). Separate analyses were performed for poor and rich
      countries as well as all countries combined. Social capital (trust) showed no
      significant association with the three health outcomes. A particularly strong
      relationship was found between Gini index and IMR for rich countries, and GNP per
      capita and life expectancy for all countries. In the group of poor countries, GNP
      per capita and Gini index in the same model were associated with IMR. The results
      contradict the suggested impact of social capital on health, and instead support
      the notion that economic factors such as absolute income and relative income
      distribution are of importance.

PMID- 17175842
TI  - Health care access in three nations: Canada, insured America, and uninsured
      America.
AB  - This analysis provides new statistics for one of the oldest and fiercest debates
      in American health policy: whose residents have better access to health care, the
      United States' or Canada's? Data from the 2002-2003 Joint Canada U.S. Survey of
      Health show that, despite major differences in their health systems, most
      Canadians and Americans get the care they need. However, one group of Americans
      is much more likely to report serious access barriers--the uninsured. About one
      third of currently or recently uninsured Americans, aged 18 to 64, said they
      could not get needed health care (over three times the rate of insured Americans
      or Canadians). Compared with Canadians and insured Americans, the uninsured are
      less likely to use hospital or physician services, and those who do are less
      satisfied with the care they receive. They are also less likely to purchase
      prescribed medications, due to cost. From a consumer perspective, the most
      salient feature of the Canadian system is its universality. In contrast, insured
      Americans under age 65 are at risk of losing their insurance and facing
      substantial access barriers.

PMID- 17175843
TI  - The impact of aging on long-term care in Europe and some potential policy
      responses.
AB  - The article examines recent data on the impact of increasing numbers of elderly
      people in Europe on expenditures for long-term care services. After reviewing
      recent and projected future costs of long-term care, the authors examine current
      national strategies for long-term care as well as potential policy options that
      could reduce future expenditures due to aging. Although long-term care
      expenditures in Europe will rise over the next several decades, countries can
      adopt a variety of strategies--many of them in social sectors outside the health
      system--to reduce or mitigate the overall effects of likely long-term care needs.

PMID- 17175844
TI  - Identifying carcinogens: the tobacco industry and regulatory politics in the
      United States.
AB  - The process of identifying carcinogens for purposes of health and safety
      regulation has been contested internationally. The U.S. government produces a
      "Report on Carcinogens" every two years, which lists known and likely human
      carcinogenic substances. In the late 1990s the tobacco industry responded to the
      proposed listing of secondhand smoke with a multi-part strategy. Despite industry
      efforts to challenge both the substance of the report and the agency procedures,
      environmental tobacco smoke was declared by the agency in 2000 to be a known
      human carcinogen. A subsequent lawsuit, launched by chemical interests but linked
      to the tobacco industry, failed, but it produced a particular legal precedent of
      judicial review that is favorable to all regulated industries. The authors argue
      that, in this case, tobacco industry regulation contradicts academic expectations
      of business regulatory victories. However, the tobacco industry's participation
      in the regulatory process influenced the process in favor of all regulated
      industry.

PMID- 17175845
TI  - Is democracy good for health?
AB  - Studies of health have recognized the influence of socioeconomic position on
      health outcomes. People with higher socioeconomic ranking, in general, tend to be
      healthier than those with lower socioeconomic rankings. The effect of political
      environment on population health has not been adequately researched, however.
      This study investigates the effect of democracy (or lack thereof) along with
      socioeconomic factors on population health. It is maintained that democracy may
      have an impact on health independent of the effects of socioeconomic factors.
      Such impact is considered as the direct effect of democracy on health. Democracy
      may also affect population health indirectly by affecting socioeconomic position.
      To investigate these theoretical links, some broad measures of population health
      (e.g., mortality rates and life expectancies) are empirically examined across a
      spectrum of countries categorized as autocratic, incoherent, and democratic
      polities. The regression findings support the positive influence of democracy on
      population health. Incoherent polities, however, do not seem to have any
      significant health advantage over autocratic polities as the reference category.
      More rigorous tests of the links between democracy and health should await data
      from multi-country population health surveys that include specific measures of
      mental and physical morbidity.

PMID- 17175846
TI  - A review of data on the U.S. health sector spring 2006.
AB  - This report presents information on the state of the U.S. health system in the
      spring of 2006. It includes data on the uninsured and underinsured and their
      access to health care, on socioeconomic inequality in health care, and on the
      rising costs of the U.S. health system. It also presents information on the role
      of corporate money in health care, focusing on the pharmaceutical industry,
      Medicare HMOs, and corporate-government conflicts of interest. The author
      includes a survey of recent public opinion polls on health care and health system
      reform and an update on the U.S. national health insurance legislation. The
      article ends by reviewing recent data on international health systems and
      international system comparisons.

PMID- 17175847
TI  - Venezuela's Barrio Adentro: an alternative to neoliberalism in health care.
AB  - Throughout the 1990s, all Latin American countries but Cuba implemented health
      care sector reforms based on a neoliberal paradigm that redefined health care
      less as a social right and more as a market commodity. These reforms were couched
      in the broader structural adjustment of Latin American welfare states as
      prescribed by international financial institutions since the mid-1980s. However,
      since 2003, Venezuela has been developing an alternative to this neoliberal trend
      through its health care reform program, Mision Barrio Adentro (Inside the
      Neighborhood). In this article, the authors review the main features of the
      Venezuelan health care reform, analyzing, within their broader sociopolitical and
      economic contexts, previous neoliberal health care reforms that mainly benefited
      transnational capital and domestic Latin American elites. They explain the
      emergence of the new health care program, Mision Barrio Adentro, examining its
      historical, social, and political underpinnings and the central role played by
      popular resistance to neoliberalism. This program not only provides a compelling
      model of health care reform for other low- to middle-income countries but also
      offers policy lessons to wealthy countries.

PMID- 17175848
TI  - Poverty rates in Venezuela: getting the numbers right.
AB  - This article looks at household and individual poverty rates in Venezuela over
      the past seven years. For more than a year, the statement that poverty in
      Venezuela has increased under the government of President Hugo Chavez has
      appeared in scores of major newspapers, on major television and radio programs,
      and even in publications devoted to foreign policy. There are no data to support
      such statements, and in fact the available data show a decline in poverty for
      both individuals and households over the seven-year period: the percentage of
      people in poverty declined from 50 percent in the first quarter of 1999 to 43.7
      percent in 2005. Further, there is no evidence to suggest any change in the
      methodology for measuring poverty during this period, as has been alleged in a
      number of reports. The article also examines briefly the impact of significant
      changes in non-cash benefits such as free health care, which are not taken into
      account in the measured poverty rate, on poor people in Venezuela. Finally, the
      authors look at how the mistakes in reporting on Venezuela's poverty rate were
      made; an appendix gives examples of mistakes in major media and foreign policy
      publications.

PMID- 17175849
TI  - Cynical hostility and the metabolic syndrome: a case-control study.
AB  - BACKGROUND: Evidence suggests that metabolic syndrome and hostility are
      independent risk factors for the development of coronary heart disease. Recently,
      the combined effect of metabolic syndrome and hostility has shown to predict the
      incidence of myocardial infarction. This study tested whether cynical hostility
      was associated with the metabolic syndrome in a sample of Italian adults.
      METHODS: 992 subjects participated in the study. Among them, 546 participants
      were classified as having metabolic syndrome and 446 as controls, not having any
      of the risk factors that constitute the metabolic syndrome. Cynicism, the
      cognitive component of hostility, was measured with a self-report questionnaire
      derived from the Cook-Medley Hostility Scale. Metabolic syndrome was based on
      having the following risk factors: obesity, hyperinsulinemia, dyslipidemia, and
      elevated arterial blood pressure. RESULTS: The cross-sectional association of
      cynical hostility with metabolic syndrome was statistically significant (p <
      0.0001). Hostility was also associated with age (p < 0.0001) and educational
      level (p < 0.02). Predictors of having metabolic syndrome were higher cynicism
      (O.R. 1.12), older age (O.R. 1.39), and lower educational level (O.R. 1.05).
      CONCLUSIONS: The results highlight the potential importance of intervention on
      psychological factors (i.e. hostility) to prevent coronary heart disease.

PMID- 17175850
TI  - [Can it really be dangerous to be exposed suddenly to high altitude without
      acclimatization?].

PMID- 17175851
TI  - Kentucky's uninsured.

PMID- 17175852
TI  - New solutions for treating chronic insomnia: an introduction to behavioral sleep
      medicine.
AB  - Insomnia is one of the most frequent complaints brought to primary care
      physicians and research suggests insomnia's prevalence is on the rise. Insomnia
      evaluation and treatment can be a time-intensive process that puts significant
      demands on a busy medical practice. To date, hypnotic medications are the most
      frequently prescribed treatment for insomnia and have been demonstrated to be
      efficacious for the treatment of acute insomnia. Cognitive-behavioral treatment
      (CBT) has been found to be just as effective as hypnotics for the treatment of
      acute insomnia and more effective for the treatment of chronic insomnia. CBT is
      now recognized as a first-line intervention for chronic insomnia, yet is
      underutilized. Many patients and healthcare providers are unaware of the efficacy
      of CBT for insomnia and currently there are few qualified providers. To address
      this need, the American Academy of Sleep Medicine (AASM) has developed a new
      subspeciality to train providers in the provision of CBT for insomnia as well as
      other sleep disorders.

PMID- 17175853
TI  - Antibiotic therapy of hospitalized patients with community-acquired pneumonia: an
      international perspective from the CAPO Cohort Study.
AB  - The American Thoracic Society and the Infectious Diseases Society of America have
      developed evidence-based guidelines for the therapy of hospitalized patients with
      community-acquired pneumonia (CAP). In an attempt to evaluate if the care
      provided to hospitalized patients with CAP is in compliance with the care
      recommended by national guidelines, an international network of investigators has
      been collecting data from 40 hospitals in 13 countries. The care provided in the
      following areas of antibiotic therapy was analyzed: empiric antibiotic therapy,
      timing of initial antibiotic therapy, and switch from intravenous to oral
      antibiotic therapy. Lack of compliance with national guidelines was identified in
      all areas of antibiotic therapy. Compliance at the local level can be improved
      with the implementation of a hospital-based pneumonia quality improvement team.
      Improving compliance with national guidelines recommendations will produce a
      beneficial effect in CAP clinical and economic outcomes.

PMID- 17175854
TI  - Effect of a BMI chart on weight management discussions in a primary care setting.
AB  - OBJECTIVE: To measure whether the addition of a BMI chart to a patient's medical
      record at the time of the office visit would increase the likelihood of a
      physician discussing weight management with the patient. METHODS: Office staff
      were instructed to place a BMI chart on the front of medical charts of all
      patients aged 21 years to 65 years who were seen during a 2-month period in two
      urban university-affiliated clinics. The staff were to plot the BMI on the chart.
      The medical records were audited for the presence of the BMI chart and any
      documentation of a discussion of weight management. RESULTS: Of the 961 charts
      that were audited, 44% contained the BMI chart. A discussion of weight management
      issues was documented in 19% of those that contained a BMI chart and in 15% of
      those that did not contain a BMI chart. CONCLUSIONS: Data presented here suggest
      that adding a BMI chart to the patient medical record may increase the attention
      of a physician to weight management issues.

PMID- 17175855
TI  - Physician, educate thyself.

PMID- 17175856
TI  - Darwin, social Darwinism, and intelligent design.

PMID- 17175857
TI  - Intelligent design and the age of endarkenment.

PMID- 17175858
TI  - From amusement to anger: Samuel Clemens's shifting attitude toward patent
      medicines.

PMID- 17175859
TI  - Gloria in absentia: Walter Reed, James Carroll, and the ethics of authorship.

PMID- 17175860
TI  - Ramshackle lopsided research.

PMID- 17175861
TI  - Frankenstein, a story of scientific discovery turned to dread, with a lesson in
      ethics.

PMID- 17175862
TI  - The sorcerer's stone.

PMID- 17175863
TI  - Defining personhood.

PMID- 17175864
TI  - The role of subspecialization in emergency medicine: a rebuttal.

PMID- 17175865
TI  - Emergency medicine is a specialty. Let's make it that, and not dilute it in order
      to be PC.

PMID- 17175866
TI  - Nalidixic acid overdose and metabolic acidosis.

PMID- 17175867
TI  - Use of lidocaine and fentanyl premedication for neuroprotective rapid sequence
      intubation in the emergency department.
AB  - INTRODUCTION: Autoregulation is dysfunctional in the injured brain. Increases in
      intracranial and arterial pressure may therefore result in extension of the
      primary injury. Rapid sequence intubation (RSI) is a well-known cause of surges
      in both arterial pressure and intracranial pressure. Neuroprotective agents,
      namely lidocaine and fentanyl, have the potential to minimize the pressure surges
      implicated in secondary brain injury. The purpose of this study was to determine
      the frequency with which neuroprotective agents were used for neuroprotective RSI
      in the emergency department. METHODS: We conducted a retrospective chart review
      of all 139 patients intubated in the emergency department of Vancouver General
      Hospital between March and October 2003. Patients were eligible if there was an
      indication for neuroprotective agents defined as presumed intracranial pathology
      and a mean arterial pressure (MAP) > 85 mm Hg. Contraindications to fentanyl
      included MAP < 85 mm Hg or allergy to fentanyl. RESULTS: Seventy-seven patients
      were intubated for primary neurological indications. Indication for intubation
      included non-traumatic causes (n = 37) (including cerebrovascular accident or
      intracranial hemorrhage) and closed head injury (n = 40). The mean age (+/-
      standard deviation) was 52.3+/-20.4 years, and 31.4% were female. Fifty-seven
      (74.0%) patients had indications for neuroprotective agents, without
      contraindications. When neuroprotective agents were indicated, lidocaine was used
      in 84.2% (95% confidence interval [CI] 72.6%-91.5%) of patients while fentanyl
      was used in 33.3% (95%CI 22.4%-46.3%) of patients. Eleven percent of the
      intubations were performed with a fentanyl dose of delta 2 mcg/kg, which is the
      lower limit considered effective. CONCLUSIONS: Despite the potential benefit of
      using lidocaine and fentanyl in appropriate patients undergoing neuroprotective
      RSI in the emergency department, our study identified a significant
      underutilization of optimal premedication. The identification of barriers to use
      and the implementation of strategies to optimize use are necessary.

PMID- 17175868
TI  - Procedural sedation and analgesia in a Canadian adult tertiary care emergency
      department: a case series.
AB  - OBJECTIVES: To examine the safety of emergency department (ED) procedural
      sedation and analgesia (PSA) and the patterns of use of pharmacologic agents at a
      Canadian adult teaching hospital. METHODS: Retrospective analysis of the PSA
      records of 979 patients, treated between Aug. 1, 2004, and July 31, 2005, with
      descriptive statistical analysis. This represents an inclusive consecutive case
      series of all PSAs performed during the study period. RESULTS: Hypotension
      (systolic blood pressure < or = 85 mm Hg) was documented during PSA in 13 of 979
      patients (1.3%; 95% confidence interval [CI] 0.3%-2.3%), and desaturation (SaO2 <
      or = 90) in 14 of 979 (1.4%; Cl 0.1%-2.7%). No cases of aspiration, endotracheal
      intubation or death were recorded. The most common medication used was fentanyl
      (94.0% of cases), followed by propofol (61.2%), midazolam (42.5%) and then
      ketamine (2.7%). The most frequently used 2-medication combinations were propofol
      and fentanyl (P/F) followed by midazolam and fentanyl (M/F), used with similar
      frequencies 58.1% (569/979) and 41.0% (401/979) respectively. There was no
      significant difference in the incidence of hypotension or desaturation between
      the P/F and M/F treated groups. In these patients, 9.1% (90/979) of patients
      received more than 2 different drugs. CONCLUSIONS: Adverse events during ED PSA
      are rare and of doubtful clinical significance. Propofol/fentanyl and
      midazolam/fentanyl are used safely, and at similar frequencies for ED PSA in this
      tertiary hospital case series. The use of ketamine for adult PSA is unusual in
      our facility.

PMID- 17175869
TI  - Emergency department procedural sedation and analgesia: A Canadian Community
      Effectiveness and Safety Study (ACCESS).
AB  - OBJECTIVES: To determine the effectiveness and safety of procedural sedation and
      analgesia (PSA) in a Canadian community emergency department (ED) staffed
      primarily by family physicians and to assess the role of capnometry monitoring in
      PSA. METHODS: One hundred and sixty (160) consecutive procedural sedation cases
      were reviewed from the ED of a rural hospital in Huntsville, Ont. The ED is
      mainly staffed by family physicians who have received in-house training in PSA.
      Safety and effectiveness measures were extrapolated from a standardized PSA form
      by a blinded research assistant. RESULTS: The mean age of the patient population
      was 33.6 years (standard deviation = 23.6). Fifty-four percent of the patients
      were male, and 33% of the cases were pediatric. PSA medications included propofol
      (84%), fentanyl (51%) and midazolam (15%), and the procedural success rate was
      95.6%. The adverse event (AE) rate was 18% and included apnea (10%), inadequate
      sedation (3%), bradycardia (2%), desaturation (1%), hypotension (1%) and bag
      valve-mask use (1%). In those aged > or = 65 years there was a greater incidence
      of apnea. There were no episodes of emesis and there were no intubations. A
      modified jaw thrust manoeuvre was used in 23% of the cases. I the 64% of cases
      where capnometry was used, there was no association between its use and any AE
      measures. CONCLUSION: Procedural sedation was safe and effective in our
      environment. Capnometry recording did not appear to alter outcomes, although the
      data are incomplete.

PMID- 17175870
TI  - Health promotion and disease prevention in the emergency department: a
      feasibility study.
AB  - BACKGROUND: Health promotion and disease prevention have been increasingly
      recognized as activities that may be within the scope of emergency medicine. The
      purpose of this feasibility study was to identify health risks and offer
      immediate interventions to adult patients who have drug and/or alcohol problems,
      incomplete immunization, are overdue for a Pap (Papanicolaou) smear, and/or are
      smokers. METHODS: The study took place in a busy tertiary Emergency Department
      (ED) serving an inner-city population with a significant proportion of patients
      who are homeless, substance abusers, working poor, and/or recent immigrants. A
      convenience sample of patients completed a computer-based health-risk survey.
      Trained health promotion nurses offered appropriate interventions to patients
      following review and discussion of their self-reported data. Interventions
      included counseling for problem drinking, substance abuse, and smoking cessation,
      screening for cervical cancer, and immunization. RESULTS: From October 20, 2000
      to June 30, 2003, we enrolled 2366 patients. One thousand and eleven subjects
      (43%) reported substance abuse and 1095 (46%) were smokers. Of the 158 smokers
      contacted in follow-up, 19 (12%) had quit, 63 (40%) had reduced the number of
      cigarettes/day and 76 (48%) reported no change. Of 1248 women surveyed, 307 (25%)
      were overdue for a Pap smear and 54 (18%) received this intervention. Forty-four
      percent of subjects were overdue for at least one immunization and of those, 414
      (40%) were immunized in the ED. CONCLUSION: At-risk patients can be identified
      using a computer-based screening tool, and appropriate interventions can be given
      to a proportion of these patients in a busy inner city ED without increasing wait
      time.

PMID- 17175871
TI  - Guidelines for the use of hypothermia after cardiac arrest.

PMID- 17175872
TI  - Evidence for the use of hypothermia after cardiac arrest.

PMID- 17175873
TI  - Prehospital intubation for patients with severe head injury: more is not
      necessarily better.

PMID- 17175874
TI  - Myth: blood transfusion is effective for sickle cell anemia-associated priapism.
AB  - OBJECTIVE: Priapism is a recognized complication of sickle cell anemia (SCA).
      When initial conventional treatments fail, simple or exchange blood transfusion
      has been advocated as a secondary intervention. However, recent literature
      suggests this may not be an effective therapy and may have significant neurologic
      sequelae. This paper reviews and summarizes the effectiveness and risks of blood
      transfusion compared with conventional priapism therapy. METHODS: All relevant
      papers identified from a MEDLINE search were systematically examined for data
      related to the use of blood transfusion in the setting of priapism due to SCA.
      The effectiveness of conventional therapy was compared with transfusion therapy
      using the outcome of "time to detumescence" (TTD). In addition, papers
      documenting adverse neurologic sequela were reviewed and summarized. RESULTS:
      Forty-two case reports were identified containing complete information with
      regard to patient age and TTD. The mean TTD was 8.0 days with conventional
      therapy (n = 16) and 10.8 days with blood transfusion therapy (n = 26). Adverse
      neurologic sequelae from blood transfusion therapy was described in 9 cases, with
      long term outcomes ranging from complete resolution to severe residual deficits.
      CONCLUSION: The current literature does not support the contention that blood
      transfusion is an effective therapy in the treatment of priapism due to SCA, as
      defined by an acceleration of TTD. In fact, numerous reports suggest that serious
      neurologic sequelae may result from this treatment. We feel the routine use of
      this therapy cannot be recommended.

PMID- 17175875
TI  - Orbital pseudotumour presenting as orbital cellulitis.
AB  - A 33-year-old woman presented to a community emergency department with a 4-day
      history of monocular orbital pain, photophobia and pain on extraocular movement.
      Findings included chemosis, conjunctival injection and restricted extraocular
      movements causing strabismus. She was diagnosed with orbital cellulitis during
      her initial emergency department visit and treated with intravenous antibiotics.
      On her second ED visit later the same day, a diagnosis of orbital pseudotumour
      was made after computed tomography revealed inflammation of the sclera, optic
      nerve, muscle and adipose tissue within the orbit. Antibiotics were discontinued
      and tapering steroids were initiated, with prompt resolution of symptoms.

PMID- 17175877
TI  - [Trends in Physiology].

PMID- 17175876
TI  - Ovarian torsion in a 20-year-old patient.
AB  - Ovarian torsion is an uncommon gynecological emergency that requires prompt
      recognition and treatment. It may present with nonspecific signs and symptoms,
      and should be considered in any female with acute abdominal pain. The diagnosis
      is based on an awareness of the relevant risk factors, the clinical presentation,
      and a high index of suspicion. Timely investigation and management can make the
      difference between ovarian loss and salvage--an outcome of great importance in
      the population of reproductive age females.

PMID- 17175878
TI  - [New pathway for glutamate release from brain glial cells upon ischemic stress].

PMID- 17175882
TI  - [Is hibernation a possible phenomenon in humans?].

PMID- 17175880
TI  - [Model lectures in physiology education].

PMID- 17175886
TI  - [Standards for animal care, custody, and reducing pain in animal experiments].

PMID- 17175885
TI  - [New guidelines and standards in revised Animal Rights Act].

PMID- 17175887
TI  - Laboratory diagnosis of norovirus.
AB  - Noroviruses are considered the most common cause of outbreaks of non-bacterial
      gastroenteritis worldwide, as well as being an important cause of sporadic
      gastroenteritis. Noroviruses were discovered by electron microscopy and this
      method played an important role in the diagnosis of noroviruses until the
      introduction of the reverse transcription-polymerase chain reaction procedure in
      the 1990's. In recent years, real time reverse transcription-polymerase chain
      reaction methodology has emerged as a potentially important diagnostic procedure.
      The recent introduction of commercial enzyme immunoassay kits has further
      broadened the range of techniques available to the diagnostic laboratory for
      detection of noroviruses. In addition, the technique of nucleic acid sequence
      based amplification shows promise. This review examines the main features of
      current diagnostic methods for norovirus identification: electron microscopy,
      reverse transcription-polymerase chain reaction, real time reverse transcription
      polymerase chain reaction, nucleic acid sequence-based amplification and enzyme
      immunoassay detection using a commercial kit.

PMID- 17175888
TI  - Hypophosphatemia and hungry bone syndrome in a dialysis patient with secondary
      hyperparathyroidism treated with cinacalcet--proposal for an improved monitoring.
AB  - Rapid correction of severe and prolonged hyperparathyroidism (HPT) by surgical
      parathyroidectomy (PTX) occasionally causes a so-called "hungry bone syndrome".
      According to the reports available in the literature, this syndrome occurs after
      PTX in patients on dialysis with severe and long-lasting secondary or tertiary
      HPT with high bone turnover, e.g. markedly raised serum alkaline phosphatase. The
      syndrome is characterized by prolonged hypocalcemia with hypocalcemic symptoms,
      as well as a usually mild decrease of serum phosphate after PTX. The syndrome is
      also known from correction of primary HPT, or persistent HPT after renal
      transplantation, and after medical treatment of thyrotoxicosis. The hungry bone
      syndrome refers to the recalcification or remineralization that occurs in bone
      after correction of HPT. The calcimimetic drug cinacalcet is a new option for the
      treatment of secondary hyperparathyroidism in patients with renal failure. We
      present a cinacalcet-treated dialysis patient with severe secondary HPT and
      raised alkaline phosphatase who developed hypocalcemia and such pronounced
      hypophosphatemia and severe diffuse bone pain ("hungry bone syndrome") during
      treatment that the drug had to be discontinued. About two months later, a second
      exposure to a low dose of cinacalcet (30 mg/d) again led to hypophosphatemia
      (serum phosphate decreased from 2.5 to 0.7 mmol/1). We recommend that the
      laboratory monitoring of cinacalcet-treated patients should include phosphate
      levels and not only intact PTH and calcium, as currently suggested.

PMID- 17175889
TI  - Cerebellar ataxia, peripheral neuropathy, "gluten sensitivity" and anti-neuronal
      autoantibodies.
AB  - "Gluten sensitive" neurological syndromes (ataxia, peripheral neuropathy, and
      other conditions) have been hypothesised in patients with various idiopathic
      neuropathologies, detectable anti-gliadin antibodies and HLA-DQ2 or DQ7. Further
      investigation of these cases has suggested a high incidence of anti-neuronal
      antibodies (anti-Purkinje, anti- neuronal nuclear, anti-GAD). This study
      investigates this contentious area. Over a two-year period, from a local UK
      population base of two million, seeing over 5000 general neurology referrals per
      year, we collected 20 cases with idiopathic ataxia, and 32 with idiopathic
      peripheral neuropathy, and referred them all for blinded antibody testing. 30
      adult healthy blood donors, and 7 cases of hereditary ataxia were used as control
      subjects. Anti-gliadin antibodies (IgG and or IgA) were found in 40% of cases
      with idiopathic ataxia, 34% with idiopathic peripheral neuropathy, 17% healthy
      blood donors and 43% with hereditary ataxia. None was positive for antiPurkinje
      cell or anti-neuronal nuclear antibodies. Only two patients with idiopathic
      ataxia were positive for antiGAD antibodies (one also being anti-gliadin
      positive). We were unable to confirm the findings of other groups. First, cases
      of so-called "gluten sensitive" neurological syndromes were extremely rare in our
      centre. Second, our idiopathic cases, whether they be gliadin antibody
      seropositive or not (i.e. "gluten sensitive" or not) were rarely neuronal
      autoantibody positive.

PMID- 17175890
TI  - Maturity-onset diabetes of the young: an update.
AB  - Maturity-onset diabetes of the young (MODY) is a dominantly inherited form of non
      ketotic diabetes. It usually develops in childhood, adolescence or young
      adulthood. The disease is heterogenous regarding the genetic and clinical
      features. Until now, 6 causal genes have been identified. According to clinical
      evidence there is at least one further MODY gene. MODY2 is caused by mutations in
      the glucokinase gene, which encodes the signal protein for insulin secretion. The
      remaining MODY subtypes are the result of mutations in genes coding for
      transcription factors. MODY2 and MODY3 are by far the most frequent forms.
      Patients with MODY2 have mild, asymptomatic and stable hyperglycemia that is
      present from birth. They rarely develop microvascular disease, and seldom require
      pharmacologic treatment. MODY3 patients usually develop severe hyperglycemia
      after puberty, which often leads to the diagnosis of diabetes type 1. Despite the
      progression of hyperglycemia, sensitivity to sulfonylureas is retained in MODY3
      patients for many years. Diabetic retinopathy and nephropathy frequently occur in
      MODY3 patients. Other risk factors are not present. The frequency of
      cardiovascular disease is not increased. Due to the pleiotropic character of the
      transcription factors most MODY subtypes are diseases with multi-organ
      involvement in addition to diabetes. MODY5 appears to be much more frequent than
      originally assumed. This form is associated with pancreatic atrophy, renal
      morphologic and functional abnormalities, genital tract malformations and
      pathological liver test. Compared to MODY2, 3, and 5, the remaining subtypes of
      MODY have a much lower prevalence. Molecular diagnosis has important consequences
      for prognosis, family screening and therapy.

PMID- 17175891
TI  - A fast and reliable single-run method for genotyping of the human cytochrome P450
      2C8 gene for different ethnic groups.
AB  - Patients vary widely in their response to drug therapy according to their genetic
      background of drug metabolizing enzymes. The cytochrome P450 enzyme CYP2C8 is one
      of the major metabolizing enzymes involved in drug metabolism and thus a
      candidate for routine pharmacogenetic screening. The aim of this work was
      establishing a fast and reliable method to detect the three CYP2C8 genotypes
      CYP2C8*2, CYP2C8*3, CYP2C8*4, and the wildtype allele. An established real-time
      polymerase chain reaction (PCR) to detect two CYP2C8 genotypes was extended by
      introduction of a third hybridization probe. After optimization of running
      conditions, the new triplex method was evaluated using 200 DNAs of African origin
      as templates. Standard methods were performed as controls. The new triplex real
      time PCR was fast, reliable and reproducible. The obtained results showed no
      deviation from the results of the established technique. The polymorphism of the
      CYP2C8 gene among an African population showed the expected distribution (68%
      wildtype gene, 32% at least one CYP2C8*2 allele). Pharmacogenetics gain
      increasing interest in routine medical care to prevent severe adverse effects or
      the application of ineffective drugs. We here provide a fast, reliable and
      reproducible method in one single assay run to detect three relevant CYP2C8
      alleles independent of the patient's ethnic origin.

PMID- 17175892
TI  - Method comparison of cardiac marker assays on PATHFAST, StratusCS, AxSYM,
      Immulite 2000, triage, elecsys and cardiac reader.
AB  - The purpose of this evaluation was to perform a method comparison of the assays
      for cardiac troponin I (cTnl), CK-MB, myoglobin, and NT-proBNP on the automated
      PATHFAST Immuno-Assay Analyzer with respective immunoassays on other commercially
      available immunoanalyzers. The PATHFAST assays are immunochemiluminescent assays
      (in single reagent cartridges) employing two mono- or polyclonal antibodies in a
      sandwich test format. The calibration materials for cTnI and CK-MB are
      standardized to the reference materials NIST SRM 2921 (troponin CIT complex) and
      IRMM-IFCC 455 (CK-MB mass). The PATHFAST assays for cTnI, CK-MB, myoglobin, and
      NT-proBNP on the PATHFAST Analyzer were compared using 118 (NT-proBNP: 90) plasma
      samples from patients with different cardiovascular diseases with those on the
      Dade Behring StratusCS Analyzer, on the Abbott AxSYM System, on the DPC IMMMULITE
      2000 Analyzer, on the Biosite Triage Meter Plus System, on the Roche Elecsys
      Immuno Analyzer 2010 and Roche Cardiac Reader System, respectively. The
      correlation coefficients for the comparison of cTnI methods ranged from 0.953 to
      0.982, those for the comparison of myoglobin methods ranged from 0.776 to 0.992,
      and those for the comparison of CK-MB methods ranged from 0.835 to 0.999, with
      the Triage System giving in all comparisons the lowest correlation. Also the
      comparison of PATHFAST NTproBNP against the Roche Elecsys assay yielded a very
      good correlation (r = 0.992). The slopes of the regression line among methods
      showed considerable variation indicating that standardization efforts by
      international groups are indispensable to achieve harmonization of results. In
      summary, this evaluation study confirms the overall good correlation of the
      results obtained with assays for cardiac markers developed on the PATHFAST
      analyzer with those on other immunoassay platforms and thus the analytical
      reliability of the developed methods.

PMID- 17175893
TI  - Monitoring cardiac function by B-type natriuretic peptide (BNP) in patients with
      infantile Pompe's disease treated with recombinant alpha-glucosidase.
AB  - Infantile Pompe's disease is a glycogen storage disorder. Untreated it is lethal
      within the first year of life. Initial clinical trials with recombinant human
      acid alpha-glucosidase (rhGAA) have shown enzyme replacement therapy to improve
      cardiac and skeletal muscle function. B-type natriuretic peptide (BNP) is a
      neurohormone released by cardiac cells and increasingly used for monitoring heart
      failure in adults. We report on two infants affected by infantile Pompe's disease
      and treated with rhGAA, in whom cardiac function was supervised by BNP
      determination during the first 52 and 26 weeks of life, respectively. In the
      first patient, BNP (normal < 50 ng/l) increased from 475 (week 4) to 2417 ng/l
      (week 13) before, and declined continuously from 2696 (week 18) to 107 (week 52)
      after initiation of rhGAA-treatment. BNP-values reflected improvement of cardiac
      function earlier than echocardiography. In the second, earlier treated subject,
      BNP-values were only moderately elevated (86 ng/1) except two determinations
      timely linked to port implantation. In both patients, BNP levels correlated well
      with the severity of heart failure when using the NYHA classification modified
      for infants. These observations illustrate that BNP may be a valuable parameter
      for surveillance of cardiac function in Pompe's disease.

PMID- 17175894
TI  - Erythropoiesis activity, iron availability and reticulocyte hemoglobinization
      during treatment with hemodialysis and in subjects with uremia.
AB  - In hemodialysis subjects correction of anemia is facilitated by combined
      supplementation of intravenous iron and recombinant human erythropoietin.
      Reticulocyte hemoglobin content (RET-He) is considered to be an actual indicator
      reflecting functional iron availability for erythropoiesis. In the present study,
      interdependence between biochemical analytes reflecting iron status and
      hemocytometric parameters indicating the degree of hemoglobinization of
      reticulocytes and red blood cells, respectively, is established. Participants of
      the study were reference subjects (n=75), subjects with iron deficiency anemia
      (n=52), subjects with uremia (n=19) and subjects undergoing hemodialysis
      treatment (n=43). If compared with the reference subjects the results for RBC
      counts and MCHC are statistically significantly decreased in case of subjects
      with hemodialysis and uremia, whereas increased results are established with
      regard to RDW-sd values. Significantly increased results for absolute
      reticulocyte counts and immature reticulocyte fractions (IRF) are also observed
      in case of subjects with hemodialysis and uremia. Slightly increased values for
      the ZPP/heme ratio in combination with elevated reticulocyte count reflect
      increased activity of erythropoiesis. At a definite MCV value, decreased levels
      for the hemoglobin content of reticulocytes (RET-He) and hemoglobin content of
      red blood cells (RBC-He) are observed in case of subjects treated with
      hemodialysis and in subjects with uremia if compared with identical MCV values of
      the group of reference subjects. For the ratio of RET-He and RBC-He obviously
      decreased results are demonstrated in case of subjects with iron deficiency
      anemia (1.02 +/- 0.08, mean +/- SD), hemodialysis (1.05 +/- 0.05) and uremia
      (1.02 +/- 0.10) if compared with the group of reference subjects (1.11 +/- 0.02).
      From the combined interpretation of the MCV values within the reference range and
      decreased values for RET-He and RET-He/RBC-He ratios, respectively, a decreased
      degree of hemoglobinization is concluded in the case of subjects with
      hemodialysis or uremia. The conclusion implicating the presumption of reduced
      functional availability of iron for hemoglobin synthesis is supported by the
      detection of increased results for sTfR concentrations and ZPP/heme ratios.

PMID- 17175895
TI  - Novel anti-carbohydrate autoantibodies in patients with inflammatory bowel
      disease: are they useful for clinical practice?
AB  - The objective of this study was to test the diagnostic accuracy of novel anti
      carbohydrate assays in patients with inflammatory bowel disease, namely in
      Crohn's disease. These carbohydrate assays are based on oligosaccharide
      chitobioside carbohydrate - anti-chitobioside carbohydrate antibodies (ACCA),
      laminaribioside carbohydrate anti-laminaribioside carbohydrate antibodies (ALCA),
      and mannobioside carbohydrate - anti-mannobioside carbohydrate antibodies (AMCA).
      We compared these assays with the anti-Saccharomyces cerevisiae antibodies (ASCA)
      assay. The results of this study suggest that ASCA are still the best serological
      marker for Crohn's disease. Further studies are required to explore the clinical
      utility of ACCA, ALCA and AMCA.

PMID- 17175896
TI  - Multicentre evaluation of performance of C-reactive protein analysis over a one
      year period.
AB  - This communication deals with a longitudinal evaluation of C-reactive protein
      (CRP) analysis during a one-year period using a single lot of liquid control sera
      (3 levels) (BIOREF-CRP levels 1, 2 and 3) in different laboratories. A total of
      652 sets of data were returned from 20 participating laboratories using 13
      different reagent-measuring device combinations. The use of the control materials
      was defined in a standard operating procedure. Data was returned to the
      organizers on a monthly basis and questions could be asked or problems presented
      during the evaluation period. Although the performance of different reagents
      varied, the control materials were shown to be stable over the whole of the
      evaluation period when stored at 4-7 degrees C in a refrigerator/cold room.
      Typical problems were encountered, examples of which are presented here in
      graphical and tabular form.

PMID- 17175897
TI  - [RiliBAK--a new computation concept].

PMID- 17175898
TI  - Recommendations for institutional prematriculation immunizations.

PMID- 17175900
TI  - High-risk drinking among college fraternity members: a national perspective.
AB  - This survey, with its 85% response rate, provides an extensive profile of
      drinking behaviors and predictors of drinking among 3,406 members of one national
      college fraternity, distributed across 98 chapters in 32 states. Multiple indexes
      of alcohol consumption measured frequency, quantity, estimated blood alcohol
      concentration levels (BACs), and related problems. Among all members, 97% were
      drinkers, 86% binge drinkers, and 64% frequent binge drinkers. On the basis of
      self-reports concerning the 4 weeks preceding the time of survey, the authors
      found that members drank on an average of 10.5 days and consumed an average of 81
      drinks. Drinkers had an average BAC of 0.10, reaching at least 0.08 on an average
      of 6 days. These fraternity members appear to be heavier drinkers than previously
      studied fraternity samples, perhaps because they were more representative and
      forthright. All 6 preselected demographic attributes of members and 2 chapter
      characteristics were significantly related to the drinking behaviors and levels
      of risk, identifying possible targets for preventive interventions.

PMID- 17175899
TI  - Characteristics of social smoking among college students.
AB  - Social smoking is a newly identified phenomenon in the young adult population
      that is poorly understood. We investigated differences in social smoking (smoking
      most commonly while partying or socializing) and other smoking within a
      convenience sample of college smokers (n = 351) from a large midwestern
      university. Results revealed that 70% of 351 current (past 30-day) smokers
      reported social smoking. No significant difference was found in motivation to
      quit between smoking groups. However, a significant difference was found between
      groups in confidence to quit, the number of days smoked, and the number of
      cigarettes smoked on those days. More social smokers than expected did not
      perceive themselves as smokers. Logistic regression analysis revealed that lower
      physical and psychological dependence and higher social support scores predicted
      social smoking.

PMID- 17175901
TI  - Barriers to reporting sexual assault for women and men: perspectives of college
      students.
AB  - The authors asked college students to rate the importance of a list of barriers
      to reporting rape and sexual assault among male and female victims. The authors'
      findings indicate that barriers prevalent 30 years ago, prior to efforts by the
      rape reform movement, continue to be considered important among college men and
      women. The barriers rated as the most important were (1) shame, guilt,
      embarrassment, not wanting friends and family to know; (2) concerns about
      confidentiality; and (3) fear of not being believed. Both genders perceived a
      fear of being judged as gay as an important barrier for male victims of sexual
      assault or rape and fear of retaliation by the perpetrator to be an important
      barrier for female victims.

PMID- 17175902
TI  - Alternative medicine and herbal use among university students.
AB  - In this study, the authors investigated the predictors of complementary and
      alternative medicine (CAM) and herbal supplement use among university students.
      They investigated demographic factors, trait affectivity, symptom reports, and
      individuals' worries about modernity as potential contributors to use of CAM and
      herbals. The authors surveyed 506 undergraduates at a large southeastern state
      universityand administered the following questionnaires to participants in a
      group setting: a CAM survey, an herbal use survey, a negative affect (NA) and
      positive affect (PA) scale, Modern Health Worries scale, and the Subjective
      Health Complaint scale. Overall, 58 % of the participants had used at least one
      type of CAM, and 79 % of the students had used at least one herbal substance in
      the past 12 months. A hierarchical regression determined that increased age,
      female gender, flu-like symptoms, musculoskeletal symptoms, pseudoneurological
      symptoms, and modern health worries were significantly related to students' CAM
      use. Herbal use was related to increased age, musculoskeletal,
      pseudoneurological, and gastrointestinal symptoms.

PMID- 17175903
TI  - Predictors of meningococcal vaccination among university students.
AB  - Invasive disease secondary to Neisseria meningitidis is a rare but devastating
      illness among university students. The Advisory Committee on Immunization
      Practices recommends educating college freshmen about meningococcal disease and
      vaccinating all college freshmen who live in residence halls. We conducted this
      survey to gain a better understanding of current immunization rates and factors
      associated with vaccination.

PMID- 17175904
TI  - Leptin as a marker of body fat and hyperinsulinemia in college students.
AB  - Little is known about obesity and insulin resistance in college students. Leptin
      is a hormone secreted by fat cells and has been shown to strongly correlate with
      both obesity and insulin resistance in children and adults. We investigated
      associations of leptin with insulin secretion and action in 119 normal-weight
      students aged 18-24 years. Leptin was strongly correlated with total fat mass (r
      = .67, p <.001), percentage body fat (r= .81, p < .001), and to a lesser degree
      Body Mass Index, or BMI, (r = .23, p < .02). Leptin was associated with fasting
      insulin (beta+/-SE = 0.30+/-0.06, p < .001) and insulin resistance (beta+/-SE =
      0.41+/-0.20, p < .001) independent of total fat, gender, and age, suggesting
      other mechanisms of leptin and insulin regulation besides obesity. Leptin
      resistance is present even among young and normal-weight college students.
      Leptin, even more so than BMI, is an important marker of adiposity and
      hyperinsulinemia in normal-weight college students and may potentially be used to
      predict type 2 diabetes.

PMID- 17175905
TI  - Smallpox-related knowledge and beliefs among recent college graduates.
AB  - Recent world events have increased concern and preparations for possible
      bioterror events. Despite worldwide efforts to limit access to bio-weapons,
      smallpox is still considered a potential bioterror threat. Americans'
      understanding of smallpox could prevent panic and enhance the willingness of
      citizens to receive vaccinations. OBJECTIVE: The authors' purpose in this study
      was to describe graduating college students' levels of smallpox-related
      knowledge. METHOD SUMMARY: Participants at a graduation ceremony--mostly female,
      with a mean age of 28.4+/-8.1 years--were handed a 35-item questionnaire that
      assessed smallpox knowledge and whether respondents would submit to vaccination
      under hypothetical circumstances. RESULTS: The convenience sample was ignorant of
      numerous facts about smallpox and unaware of government efforts to prepare for an
      attack, answering an average of 3.8 out of 10 items correctly. CONCLUSION: These
      findings raise concern because, in a smallpox event, prompt responses to
      directives of public health officials will be necessary to maximize the
      effectiveness of response plans.

PMID- 17175906
TI  - [Autowave mode of functioning of the system nitric oxide + free iron + thiols may
      ensure the regulation of biological action of nitric oxide and its endogenic
      compounds].
AB  - It has been shown earlier that, in a system NO + Fe2+ + thiols in aqueous
      solution, an oscillatory mode of changes with time in the concentration of
      paramagnetic dinitrosyl iron complexes with thiol-containing legends and S
      nitrosothiols formed in this system and in the concentration of free iron (not
      included into dinitrosyl iron complexes) can be realized. It is assumed that, in
      this system, autowaves can arise, which ensure periodic changes with time and
      space in the concentration of the system constituents. These changes may underlie
      the regulation of the physiologic effect of nitric oxide, dinitrosyl iron
      complexes, and S-nitrosothiols as agents affecting various intracellular and
      tissue targets.

PMID- 17175907
TI  - [Protonation of nitrite is an obligatory stage in the generation of nitric oxide
      from nitrite in biological systems].
AB  - The yield of nitric oxide from 1 mM sodium nitrite differs 200 times when the
      process was initiated by 10 mM sodium dithionite in the solution of 5 or 150 mM
      HEPES-buffer (pH 7.4). Dithionite acted both as a strong reductant and an agent
      that induced a local acidification of solutions without notable change in pH
      value. The amount of nitric oxide was estimated by the EPR method by measuring
      the incorporation of nitric oxide to water-soluble complexes of Fe with N-methyl
      D-glucamine dithiocarbamate (MGD), which led to the formation of EPR-detectable
      mononitrosyl iron complexes with MGD (MNIC-MGD). Ten seconds after dithionite
      addition, the concentration of MNIC - MGD complexes reached 2 microM in 5 mM
      HEPES-buffer in contrast to 0.01 microM in 150 mM HEPES-buffer. The difference
      was suggested to be due to a higher life-time of zones with decreased pH values
      in a weaker weak buffer solution. The life-time was high enough to ensure the
      protonation of a part of nitrite. The resulting nitrous acid was decomposed to
      form nitric oxide. The difference in the formation of nitric oxide from nitrite
      was also observed in weak and strong buffer solutions in the presence of
      hemoglobin (0.3 mM) or serum albumin (0.5 mM). However, the ratios of nitric
      oxide yields in weak and strong buffer did not exceed 3-4 times. The increase in
      the formation of nitric oxide from nitrite was characteristic for the solutions
      containing both proteins. Large amounts of nitric oxide formed from nitrite was
      observed in mouse liver preparation subjected to freezing-thawing procedure
      followed by incubation in 150 mM HEPES-buffer (pH 7.4) and addition of
      dithionite. The proposition was made that the presence of zones with low pH value
      in cells and tissues can ensure the predominant operation of the acid mechanism
      formation of nitric oxide from nitrite. The contribution of the formation of
      nitric oxide from nitrite catalyzing with heme-containing proteins nitrite
      reductases can be minor one under these conditions.

PMID- 17175908
TI  - [The application of PS II model for the analysis of fluorescence yield transients
      induced by actinic single turnover flash in the time range from 100 ns to 10 s].
AB  - Changes in flash-induced fluorescence yield in preparations of thermophilic
      Chlorella pyrenoidosa Chick cells (native and in the presence of DCMU) were
      investigated in the time range from 100 ns to 10 s using a new measuring system.
      The results were analyzed by mathematical modeling of processes in photosystem
      II. It was shown that the detailed description of recombination (including
      nonradiative) processes in photosystem II is important to simulate the
      fluorescence yield transients induced by an actinic single turnover flash. The
      model photosystem II parameters were modified to describe the light-induced
      effects in the presence of DCMU. By comparing the theoretical fluorescence curves
      with experimental ones, we obtained the values of relative fluorescence yield and
      the FM/F0 ratio, which is typical for experimental data. As a result of
      simulation, the values of the model parameters (rate constants of electron
      transfers at the donor and acceptor sites of photosystem II, pH in stroma,
      initial redox state of the plastoquinone pool, the rate of plastoquinol
      oxidation, and the rate constants of nonradiative recombination processes) were
      determined.

PMID- 17175909
TI  - [Transient currents and Ca2+ gradient relaxation in characean algae cells: theory
      and experiment].
AB  - Transient Ca2+ and Ca2+-dependent Cl- currents of plasmatic membranes of voltage
      clamped Chara corallina freshwater alga cells were studied. Our earlier described
      method was used for rapid (approximately 10 ms) injection of Ca2+ ions into the
      cell during the deactivation period of calcium channels following their
      activation by a positive voltage pulse (injection by "tail" Ca2+ current). This
      procedure allowed one to determine the amplitude of the Ca2+ component, as well
      as the amplitude and kinetics of the submembrane Ca2+ concentration-dependent Cl-
      component for the transient current. Calculations based on the cell model
      allowing for Ca2+ diffusion, the Ca2+-buffering properties of the cytoplasm, and
      the nonlinear dependency of iCl on [Ca2+]cyt, as well as the presence of
      chloroplasts agreed well with the experimentally observed behavior of the
      transient current. The slow stage of the [Ca2+]cyt relaxation to the resting
      level (approximately 10(-7) M), related to the functioning of Ca2+-ATPases, was
      shown to take approximately 10(2) s. We assume this stage to determine the
      duration of the refractory period after the generation of action potential.

PMID- 17175910
TI  - [Detection of new two-membrane structures in native mitochondria by the method of
      small-angle scattering of neutrons].
AB  - The structure of mitochondrial cristas has been studied for the first time by the
      method of small-angle scattering of thermal neutrons. Experiments were performed
      on intact functioning rat liver mitochondria. Mitochondrial cristas are usually
      considered as folds of the internal membrane with arbitrary nonfixed
      intermembrane distances. It was shown that, under particular conditions, during
      low-amplitude swelling of mitochondria, cristas are transformed to bimembrane
      structures, with the distance between the central planes of membranes of 190 E.
      It was found that the formation of bimembrane structures and their structural
      parameters do not depend on the method of induction of swelling, by placing the
      mitochondria into a hypotonic medium or by the opening of nonspecific pores.

PMID- 17175911
TI  - [Soliton-like and non-soliton regimes of interaction of taxis waves (illustrated
      with an example of bacterial population waves)].
AB  - It has been shown in our previous studies that, during collision, bacterial
      population waves can penetrate each other or stop. In the present study, the
      mechanism of the two regimes of interaction is considered in detail. Based on the
      experimental and theoretical research, it has been shown that this interaction is
      a vivid example to confirm one of the characteristic properties of waves in cross
      diffusion systems.

PMID- 17175912
TI  - [Mechanosensitivity of gramicidin A channels in semispherical bilayer membranes
      at constant tension].
AB  - Mechanoelectrical transduction in gramicidin A channels was studied in
      macroscopic planar lipid bilayer membranes bulged at constant tension. We found a
      supralinear increase in the single channel activity, which was proportional to
      the square of membrane radius but could not be accounted for by the increase in
      membrane surface area or by recruitment of new channels. When being extrapolated
      to biological membranes, these observations may suggest that the activity of
      permeability of ion channels can be influenced simply by changing the shape of
      the membrane, with or without stretching.

PMID- 17175913
TI  - [Identification of nonlinear models of biological membranes by the method of
      fixed voltage].
AB  - A mathematical substantiation of the method suggested by Hodkin and Huxley in
      1952 for the identification of nonlinear systems is presented. A procedure for
      the application of this method was developed, which involves creating the
      structure of a mathematical model, carrying out a series of tests with specially
      chosen signals, and finding the unknown parameters. The basic requirements to
      admissible sets of entrance and target signals and the operator of the system
      were determined. It was shown that it should be quite continuous, the minimal
      number of unknown parameters and the minimal complexity of structure of the
      operator should provide the required quality of approximation. The merits and
      demerits of the mathematical models of Hodkin-Huxley and Noble, and the
      procedures used for their creation are discussed. The structure of the operator
      for the identification of mathematical models of excitable membranes when a large
      number of membrane currents is considered is offered. It was found that nonlinear
      electric properties of biological membranes can be identified using tests with
      other kinds of "fixed" parameters, for example, the method of "fixed" current,
      the fixed linearly increasing voltage, and others.

PMID- 17175914
TI  - [Magnetophoresis and magnetic susceptibility of HeLa tumor cells].
AB  - A method for measuring the magnetic susceptibility of separate cells has been
      theoretically developed and implemented in experiments. It is based on fitting
      the videocomputer and predicted data for the integral motion curve of cells that
      settle in a fluid along a thin ferromagnetic bar by the action of a uniform
      magnetic field. The magnetic susceptibility of HeLa tumor cells and culture
      medium 199 has been measured.

PMID- 17175915
TI  - [Population dynamics: limits of predictability].
AB  - Problems pertaining to the complex character of ecological system dynamics are
      discussed. Examples of the complex dynamics of plankton populations in a
      heterogeneous environment and agricultural ecosystems under invasion of pests
      resistant to Bt toxins produced by genetically modified insecticidal crops are
      given.

PMID- 17175916
TI  - [Modeling of mechanoelectric coupling in cardiomyocytes in norm and pathology].
AB  - We developed mathematical models of the electromechanical function of
      cardiomyocytes and the simplest mechanically heterogeneous myocardial systems,
      muscle duplexes. By means of these models we studied the contribution of
      mechanoelectric feedbacks to the contractile activity of the myocardium in norm
      and pathology. In particular, we simulated and clarified the effects of
      mechanical conditions on both the form and the duration of the action potential
      during contractions. From this standpoint different kinds of myocardium
      mechanical heterogeneity were analyzed. As we have established, the latter can
      play both a positive and a negative role, depending on the distribution of
      mechanical nonuniformity and the sequence of activation of heterogeneous
      myocardium system elements. By means of the same models, we studied the
      contribution of mechanical factors to the arrhythmogenicity in the case of the
      cardiomyocyte calcium overload caused by the attenuation of the sodium-potassium
      pump and outlined the ways for correcting the contractile function in these
      disturbances.

PMID- 17175917
TI  - [Pharmacological analysis of anti-inflammatory effects of low-intensity extremely
      high-frequency electromagnetic radiation].
AB  - The anti-inflammatory effect of low-intensity extremely high-frequency
      electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2) was compared with the
      action of the known anti-inflammatory drug sodium diclofenac and the
      antihistamine clemastine on acute inflammatory reaction in NMRI mice. The local
      inflammatory reaction was induced by intraplantar injection of zymosan into the
      left hind paw. Sodium diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg or
      clemastine in doses of 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg were injected
      intraperitoneally 30 min after the initiation of inflammation. The animals were
      whole-body exposed to EHF EMR for 20 min at 1 h after the initiation of
      inflammation. The inflammatory reaction was assessed over 3 - 8 h after the
      initiation by measuring the footpad edema and hyperthermia of the inflamed paw.
      Sodium diclofenac in doses of 5 - 20 mg/kg reduced the exudative edema on the
      average by 26% as compared to the control. Hyperthermia of the inflamed paw
      decreased to 60% as the dose of was increased diclofenac up to 20 mg/kg. EHF EMR
      reduced both the footpad edema and hyperthermia by about 20%, which was
      comparable with the effect of a single therapeutic dose of diclofenac (3 - 5
      mg/kg). The combined action of diclofenac and the exposure to the EHF EMR caused
      a partial additive effect. Clemastine in doses of 0.02-0.4 mg/kg it did not cause
      any significant effects on the exudative edema, but in a dose of 0.6 mg/kg it
      reduced edema by 14 - 22% by 5 - 8 h after zymosan injection. Clemastine caused a
      dose-dependent increase in hyperthermia of inflamed paw at doses of 0.02-0.2
      mg/kg and did not affect the hyperthermia at doses of 0.4 and 0.6 mg/kg. The
      combined action of clemastine and EHF EMR exposure caused a dose-dependent
      abolishment of the anti-inflammatory effect of EHF EMR. The results obtained
      suggest that both arachidonic acid metabolites and histamine are involved in the
      realization of anti-inflammatory effects of low-intensity

PMID- 17175918
TI  - [Biophysical models of the heart electrical activity].
AB  - Based on the fundamental knowledge of the space-temporal organization of
      extracellular electrical fields of the myocardium, a system for 3-D computer
      modeling of the cardiac electrical activity at different structural levels of the
      object is being developed at the Institute of Theoretical and Experimental
      Biophysics. The system is based on the earlier proposed and modified biophysical
      model of the electrocardiosignal genesis represented by a double electrical layer
      along the surface of the electrically active myocardium. The system combines the
      model for activation and repolarization of the heart ventricles; the advanced
      model for the evaluation of parameters of the cardiac electric field, which makes
      it possible to derive model electrocardiosignals both in the direct regime of
      calculation of the potentials and in the regime of calculation of
      electrocardiosignals from preliminarily determined components of the multipole
      equivalent electrical heart generator; a database for the model parameters and
      their combinations in the form of cards of simulated "patients", and a database
      of modeled electrocardiosignals. In the present paper (first from three within
      the framework of the problem), simulation methods in electrocardiology are
      briefly described and a biophysical model of the heart electrical activity is
      presented, which has made up the basis of the system for computer modeling of
      forward and inverse problems of the cardiac electric field. The parameters of the
      model are electrophysiological, anatomical, and biophysical characteristics of
      the heart.

PMID- 17175919
TI  - [The effect of fluctuations of the electric potential on the activity of SAN
      cells].
AB  - The effect of fluctuations of the transmembrane potential on the generation of
      the action potential has been studied using a computer model of a SAN cell. It
      was shown that the magnitude of the effect increases with increasing
      concentration of acetylcholine. The effect is well seen near and after the
      cessation of spontaneous oscillations. While applying and washing acetylcholine,
      a hysteresis loop has been observed.

PMID- 17175920
TI  - [Rhythmogenesis in the sinoatrial unit of the heart].
AB  - The most significant experimental data about the formation of a uniform rhythm of
      the sinoatrial unit of the heart for both the intact sinoatrial unit of the heart
      and cardiomyocytes in cellular structures are presented. The basic mathematical
      models for studying the processes of synchronization in the sinoatrial unit of
      the heart are described, including equations of Noble, Bonhoffer, and van der Pol
      and modified axiomatic models. The basic results obtained using the mathematical
      models are presented. The major reasons influencing the formation of a uniform
      rhythm were revealed: the form of a potential pacemaker in the phase of slow
      diastolic depolarization, its porosity, the force of connection between pacemaker
      and electric capacity of pacemakers. A study of rhythmogenisis on the basis of
      the modified axiomatic model was carrud out. The method allows one to calculate
      the uniform rhythm of the sinoatrial unit of the heart in view of the mutual
      influence of pacemaker cells, including the force of connection, electric
      capacity of cells, their possible clusterization. It was shown that generally the
      uniform rhythm of the sinoatrial unit of the heart is formed on an intermediate
      level of all pacemaker cells.

PMID- 17175921
TI  - [A study of synchronization of the sinus unit upon stimulation from auricles].
AB  - The excitation of the sinoatrial unit from heart auricles of the frog has been
      studied. Potentials were recorded by means of microelectrodes inserted to
      pacemaker of the sinoatrial unit. It has been established that auricles can
      impart the rhythm to the sinoatrial unit due to electric and electromechanical
      influence, and electromechanical influence is of greater significance. Specific
      transitions accompanying the establishment of the stationary rhythm have been
      studied. A mathematical model of transitions of the establishment of the rhythm
      of the sinoatrial unit, which is based on diophant methods is offered. The
      catculations performed by means of the mathematical model coincide well with
      results of experimental studies. The stabilizing role of auricles in the
      formation of the rhythm of the sinoatrial unit has been established.

PMID- 17175922
TI  - [Parallel structures in multidimensional networks].
AB  - What restrictions does the space dimension impose on a variety of
      multidimensional regular networks? The parallel representation method is used to
      answer this question. An analytical relation of regular network dimension with
      the connectivity of vertices and the perimeter of elementary contours has been
      established. It has also been shown that a infinite dimensional network is
      equivalent to an infinite tree. In addition, the problem of closed regular
      polytops inside networks is discussed.

PMID- 17175923
TI  - [Problems of structural and functional identification of biological tissues].
AB  - The theoretical methods of identification of topological and functional
      parameters for biological tissues, such as myocardium, are considered. Among the
      unknown topological parameters are the dimension and connectivity of a network,
      and the unknown functional parameters include the electrical resistance of the
      cellular membrane and cytoplasm. Experimentally known data are the sizes of cells
      (length and diameter), the input resistance of tissue, and also the field of
      electrical potential formed by a "dot" current source (by an intracellular
      microelectrode).

PMID- 17175924
TI  - [Use of antimuscarinics in patients with lower urinary tract symptoms for BPH and
      overactive bladder].

PMID- 17175925
TI  - [External beam radiotherapy on locally advanced prostate carcinoma following
      iliac staging lymphadenectomy].
AB  - INTRODUCTION AND OBJECTIVES: Locally advanced prostate cancer supposes a high
      risk condition of post-treatment progression due to the limit situation that
      represents. Our purpose was to analyze prognoses factors in function of
      progression probability after using a treatment with external source radiotherapy
      on patients with this kind of tumors. MATERIAL AND METHODS: We retrospectively
      reviewed a set of 128 patients submitted to pelvic staging limphadenectomy prior
      to accomplish an external radiotherapeutic treatment. We employed the Kaplan
      Meier curves to study the probability of progression, logarithmic ranks test were
      used for detection of possible statistically significant differences and
      proportional risks Cox model was employed to study possible risk factors of
      progression (employing astro criteria). RESULTS: 5 years freedom probability from
      progression was of 49,93%; in spite of appreciating important differences in the
      groups stratified by the predictive variables used (total PSA, gleason of
      pathological biopsy, clinical stage and % of cores affection on biopsy), none of
      them reached statistical meaning, being the level of total PSA the closest to it.
      CONCLUSIONS: The external radiotherapeuthic treatment represents a valid
      alternative in the treatment of locally advanced prostate cancer, with a
      tolerable index of secondaries. It must be used combined with hormonotherapy. It
      seems that the use of higher radiation doses, in a safer way thanks to 3D
      conformed radiotherapy, allows to improve the results. The most powerful clinical
      predictor of evolution must be the total PSA.

PMID- 17175926
TI  - [Comparative study between tobramicin and tobramicin plus ciprofloxacin in
      transrectal prostate biopsy prophylaxis].
AB  - INTRODUCTION AND OBJECTIVES: To compare the efficacy of tobramicin and tobramicin
      + ciprofloxacin for prevention of transrectal prostatic biopsy infectious
      complications. We revised our complications, microorganism most common in the
      infectious complications, and their sensibility. MATERIAL AND METHODS:
      Prospective and randomized study in 153 patients with 157 prostatic biopsies. The
      71 patients in group A were treated with intramuscular tobramicin 100 mg, one
      dose 30 minutes before biopsy and another one 8 hours afterwards. The 85 patients
      in group B were treated with the same tobramicin doses and oral ciprofloxacin 500
      mg, one dose 30 minutes before biopsy and afterwards they continue with the
      ciprofloxacin every 12 hours during 3 days. RESULTS: we did 71 biopsies in group
      A and 86 in group B. 50 (31,8%) patients had hematuria, 20 (12,7%) fever, 15
      (9,5%) hemospermia, 7 (4,4%) perineal pain, one (1,2%) orchiepididymitis and
      another one (1,2%) urinary retention. The patients who had fever were 15 of the
      group A and 5 of the group B (p=0,004). A total of 15 (21,1%) patients with fever
      of the group A needed to be treated in the hospital and 3 patients (3,5%) of the
      group B (p=0,0006). E. coli growthed in 67% of the blood cultures and amoxicillin
      clavulanic, tobramicin and third generation of cephalosporins were the
      antibiotics more eficacious. CONCLUSIONS: Prophylaxis scheme with tobramicin plus
      ciprofloxacin was more efficacy that tobramicina alone in transrectal prostatic
      biopsy. Hematuria was the most common complication. E. coli was the microorganism
      most frequent in infectious complications after prostatic biopsy and amoxicillin
      clavulanic, tobramicin and third generation of cephalosporins the most effective
      antibiotics in our hospital.

PMID- 17175927
TI  - [Prognostic value of E-cadherina, beta catenin, Ki-67 antigen and p53 protein in
      the superficial bladder tumors].
AB  - INTRODUCTION: The natural history of the superficial carcinoma of bladder is
      characterized by his high rate of recurrence and by the aptitude to progress to
      higher stages. We are going to investigate the capacity of prediction for tumor
      recurrence of protein p53, antigen Ki-67, E Cadherin and Beta Catenin MATERIAL
      AND METHOD: 88 T1 tumors with a median of free time of disease of 36 months. 58%
      of the serie has received prophylactic treatment with BCG 81 mg. weekly for six
      weeks. Cut-oof level for For P53 and Ki-67 is 10 % of stained cells. For E
      Cadherin and Beta Catenin we have established two groups: one with the values 0-4
      (negative), and other one with the values 5-8 (positive). RESULTS: Recurrence
      rate 31%, stage progression 3%. Ki-67 expression is correlated with grade (p
      .002) and lymphatic permeation (p .028). Multiplicity is correlated with lack( of
      Cadherin and Catenin's expression. Only Ki-67 expression (p .049) and lack of
      Beta Catenin expression (p .039) reach statistical significance. In multivariant
      study only lack of Beta Catenin's expression shows independent recurrence value
      (p .049; O.R: 2,4-6,9) CONCLUSIONS: The most useful prognmostic markers are Ki-67
      and Catenina Beta Only Beta Catenin Beta shows independent value for tumour
      recurrence. Tumors wich lack expression for Catenin B or Cadherin E have lower
      recurrence free time.

PMID- 17175928
TI  - [Lasers in urology].
AB  - The objective of this article is to quote under the form of a document the
      opinions expressed by the participants of the round table "Lasers in Urology
      Today" (january 2006). The material and method used is the compilation of
      critical and updated notions on the usefulness of lasers in urology, supplemented
      by bibliographic references, a limited iconography. The results achieved by
      lasers today enable us to state that: Holmium laser is the choice treatment for
      in situ lithotripsy; however, it has not significantly improved previous results
      when treating urologic tumours and stenoses. Nowadays we have two types of
      lasers: KTP and HoL, which obtain results similar to surgery regarding BPH, but
      with reduced morbidity. The usefulness of laser in laparoscopic surgery is still
      under development. CONCLUSION: Lasers in Urology Today play an active role in in
      situ lithotripsy (HoL), and a competitive one in BPH surgery (KTP and HoL).
      Regarding the rest of indications, i.e. tumours, stenoses, laparoscopic surgery,
      etc., further studies and enough follow-up times are still needed.

PMID- 17175929
TI  - [The low hydraulic pressure transurethral resection of the prostate results in
      340 patients with great adenomas].
AB  - INTRODUCTION: the transurethral resection of prostate TURP is the elective
      treatment for the small and medium adenomas. In this study they analyse the
      effectiveness, the results and the postoperative morbidity in the resection of
      the great adenomas. PATIENTS AND METHOD: We study 340 patients with great
      adenomas and symptomatic infravesical obstruction that were operated with the low
      hydraulic pressure RTUP between August of 1999 and June of 2006. RESULTS: Average
      Age of the patients 69 years (range 51-89). Prostate volume by TRUS, 107 ml (70
      204). PSA 7,94 ng/ml (0,71-26,4). Weight of the resected fragments: 74,5gr. (50
      160), time of the intervention 65 min. (35-155), postoperative urethral
      catheterisation 1.7 days (1-8), suprapubic derivation 6.5 days (5-15), the
      duration of hospital stay after surgery were 8 days (7-16), peak flow pre-op.
      11.2 ml/sec. (5-15,7), post-operative 19.7 ml/sec. (7-41,3). There were no cases
      of TURP syndrome in this group. Operative complications: Urinary infection
      without fever (bacteria >100.000) 95 patients (27.9%), bladder derivation by
      preoperative urinary retention 53 patients (15,6%). 18 patients (5,3%) with
      postoperative urinary retention. 11 patients (3,2%), with infection and fever >38
      degrees C. 7 patients (2%) with postoperative bladder bleeding, 2 patients (0,6%)
      with urethral lesion. 1 patient (0.3%), with massive scrotal hematoma (after
      vasectomy). Control of the pre and post operative hemoglobin: Hemoglobin pre-op
      15 g/dl (12-19,3), hemoglobin post-op 11,5 g/dl (7,6-16,4), difference of (-
      3,5g/dl) 23,3%. In only 29 patients (8.5%) it was necessary to carry out a
      sanguineous transfusions (heterolog) of 2 to 4 EC (500 ml), the TRUS was 125 ml,
      weight of the fragments 90 gr. (52-140), the hemoglobin pre-op was 14,72g/dl and
      post-op of 8,8g/dl with a difference of (- 5,92g/dl) 40.2%. CONCLUSIONS: The
      video assisted low hydraulic pressure TURP, is an effective method in the
      surgical treatment of great prostate adenomas. The severe postoperative
      complications are little, and in 311 patients (91.5%) it was not necessary
      sanguineous transfusion. The stationary treatment and the urethral
      catheterisation is smaller in comparison with the open adenomectomy.

PMID- 17175930
TI  - [Nosocomial infection and infection of the surgical site in a third level
      hospital (2002-2005)].
AB  - INTRODUCTION: Nosocomial infection rates constitute an indicator of welfare
      quality, permitting to adopt measures of prevention and control. It has been
      developed a surveillance plan of the nosocomial infection in hospitals, showing
      to be an efficient method to diminish its incident. OBJECTIVE: To know the
      indicators and characteristics of the nosocomial infection and of the infection
      of the site surgical particularly, in a urology service in a global form and by
      procedures. MATERIAL AND METHODS: Prospective study by means of the
      epidemiological surveillance system from 2002 to 2005 in 4.618 patients
      hospitalised at least 24 hours, with a total of 3.096 surgical. RESULTS: The
      overall incidence of nosocomial infection was 6,10%, 3.42% for urinary infection
      and 2,81% for the infection of the chirurgical site. For procedures, the
      incidence of the infection of the surgical site for cistectomy was 22,8%, 6,6%
      for surgery of kidney and ureter and 4,36% for open surgery of prostate.
      Eschericia Coli (43,6%) was the most frequently isolated organism, accounting for
      43,6% of the causative organisms in the infection of the surgical site and 43,6%
      in the urinary infection. Pseudomonas aeruginosa is the next organism in
      frequency with a 15% in both infections. CONCLUSION: Our nosocomial infection
      rates are lower than the published standard values. The main infection rate of
      the surgical sites present in the most complex surgical techniques, whereas
      Escherichia Coli is the most frecuently isolated ethiological agent. The
      surveillance of the infection of the surgical site and related factors permit to
      incorporate improvements in the clinical-surgical practice which will be an
      indicator of reference in subsequent analysis.

PMID- 17175931
TI  - [Genitourinary diseases mortality in mercury miners].
AB  - OBJECTIVES: To study the mortality due to genitourinary diseases in mercury
      miners. POPULATION AND METHODS: 3.998 workers exposed to mercury in Minas de
      Almaden y Arrayanes S.A. were studied. The follow-up period was a century, since
      1,895 to 1,994. It was completed assessing the vital status and the basic cause
      of death, in case of fatalities. Standardized Mortality Ratios by age, sex and
      calendar period were calculated. Expected deaths were obtained from age, sex and
      calendar period specific rates for the Spanish and Castilla-La Mancha
      populations. RESULTS: A significant increase in mortality due to genitourinary
      diseases was found (CIE-9 codes 580 to 629), being significant with respect to
      the total population for nephritis, nephrotic syndrome and nephrosis, with SMR of
      1.69 an 95% CI 1.18 to 2.34. Mortality excesses due to nephritis, nephrotic
      syndrome and nephrosis were higher in the metallurgy workers than in miners. A
      Poisson multivariate regression detected a positive trend in the mortality due to
      nephritis and nephrosis associated to the exposure length, with the risk
      increasing fivefold after 30 years of exposure to mercury. CONCLUSIONS: This
      paper shows an excess in the mortality due to genitourinary diseases, specially
      in nephritis, nephrotic syndrome and nephrosis, whose estimation and significance
      increases when compared to the population of Castilla-La Mancha.

PMID- 17175933
TI  - [Laparoscopic surgery in the treatment of adrenal pathology: experience with 200
      cases].
AB  - OBJECTIVE: We report our experience in laparoscopic adrenalectomy, after adopting
      the laparoscopic technique for 10 years as a primary option for suprarenal
      surgery. METHODS: We included 200 laparoscopic adrenal surgeries performed
      consecutively in 183 patients with surgical adrenal pathology between November
      1994 and November 2005. Sixty-seven (36.6%) patients were male and 116 (63.4%)
      were female, with an average age of 49.1 years (age range 8 months to 78 years).
      RESULTS: The most frequents clinical diagnosis were hyperaldosteronism (17.5%),
      metastatic cancer (15.8%), pheochromocytoma (15.3%), Cushing syndrome (7.1%),
      adrenal cyst (4.9%) and myelolipoma (2.7%). A total of 164 total adrenalectomies,
      29 partial adrenalectomies and 7 marsupializations of adrenal cysts were
      performed. Mean surgical time was 82.6 minutes (range 25 to 240 minutes) and mean
      hospitalization time was 2.5 days (range 1-10 days). The size of the suprarenal
      gland and/or tumor varied between 1 and 14 cm (average 5.6 cm). The rate of
      complication was 6%. In 8 of the patients, there was another laparoscopic
      procedure besides the adrenal surgery: cholecystectomies (2), marsupialization of
      a renal cyst (2), block nephrectomy (2), partial nephrectomy for a tumor (1) and
      pancreatic cystectomy (1). One patient underwent a right laparoscopic
      adrenalectomy and an ipsilateral percutaneous nephrolithotomy. CONCLUSION: The
      accumulated experience with 200 laparoscopic adrenal procedures has allowed the
      management of endocrine pathologies, such as, aldosteroma, pheochromocytoma,
      Cushing syndrome and rare entities, such as, cysts, myelolipomas in a suitable
      manner. Additionally, it has permitted us to extend the benefits of a minimally
      invasive procedure for large adrenal masses and selected oncology cases.

PMID- 17175932
TI  - [Opened vs. laparoscopic radical nephrectomy in renal adenocarcinoma cost
      comparison].
AB  - PURPOSE: To undertake a cost comparison (cost minimization) between
      transperitoneal laparoscopic and opened nephrectomy in renal adenocarcinoma
      treatment. METHOD: Retrospective study on the first 26 patients submitted to LN
      without intra or postoperative complications in the period 2002-2003, using as
      control 22 patients treated with ON with the same characteristics and in the same
      period. Demographic variables were evaluated (age, sex, tumor size, etc.),
      intraoperative (operative time and fungible material used) and postoperative
      (length of stay in Postanaesthesic Care Unit, Acute Pain Unit needs and hospital
      stay). Our Hospital costs plus those imputed during year 2003 to the Urology
      Service, as well as the cost of fungible material for the same year were applied,
      carrying out a comparison of costs between both groups. RESULTS: There were no
      differences between the demographic variables between both groups except in the
      tumor, bigger size in the opened nephrectomy (p=0,001). Transperitoneal
      laparoscopic was 29,4% globally more expensive than opened nephrectomy. The
      transperitoneal laparoscopic intraoperative cost (operating room, anesthesia and
      fungibles) the exceeded in 151,6% to that of the opened nephrectomy, whereas in
      the opened nephrectomy the postoperative cost was a 63 % higher than in the
      transperitoneal laparoscopic cases. CONCLUSIONS: Transperitoneal laparoscopic in
      our Center is more expensive than opened nephrectomy due to a major occupation of
      operating room and that the specific fungible material used at the surgical act
      has a very high cost. It would be necessary to drastically reduce surgical time
      and decrease fungible material expenses, thus transperitoneal laparoscopic
      procedure could be competitive in our Hospital.

PMID- 17175934
TI  - [Management endourologic of pyeloureteral junction stenosis].
AB  - OBJECTIVES: To report our experience with endourologic methods in the treatment
      of pyeloureteral stenosis in children. MATERIALS AND METHODS: From July 2004, 7
      patients from 9 months to 15 years old with pyeloureteral junction stenosis (PUJ)
      diagnosis underwent endourologic repair. An endourological dilatation was made
      under radioscopic control. The procedures consist of an initial cystoscopy with a
      retrograde placement of catheter (4 or 5 Fr) and the guide wire (0,014''-or
      0,035''). The high pressure balloon (3 to 5 Fr) was then railroad over the wire
      and positioned across the stenosis for dilatation. A double J stent (3 to 6 Fr)
      was then introduced, remaining it during 6 weeks. RESULTS: There was no
      intraoperative complications. Median inhospital stay was 2 days (range, 2 to 8).
      The double J stent was removed without complications. All patients are
      asymptomatic with improvement in excretion times (MAG3 renography) and antero
      posterior renal pelvis diameter (ultrasound measurement). CONCLUSIONS: Balloon
      dilatation is a viable option in the management of PUJ obstruction even in
      children under one year old, with minimal morbidity.

PMID- 17175935
TI  - [Urinary undiversion; Bricker to Studer. With regard of two cases].
AB  - We present two cases of urinary undiversion from an ileal loop (Bricker) to an
      orthotopic neobladder. Due to miss adaptation to the stoma, two patients demanded
      reconversion to a continent urinary diversion. We proceed to change their urinary
      diversion to an ileal neobladder (Studer), one by open surgery and the other by
      laparoscopic surgery. In both cases immediate postoperative went uneventful. Both
      patients are continent, satisfied with their new situation, and without metabolic
      complications. Urinary undiversion from an ileal conduit to an orthotopic
      neobladder is technically feasible by open or laparoscopic surgery. It is a valid
      alternative for patients with complications due to their urinary diversion or
      miss adaptation to the cutaneous stoma.

PMID- 17175936
TI  - [Primary psoas abscess due to Streptococcus pneumoniae].
AB  - INTRODUCTION AND OBJECTIVES: To report to the literature a new case of primary
      psoas abscess. METHODS: The patient is a 65 years old woman who suffered back and
      left hip pain for approximately 1 month. A CTA showed a retroperitoneal mass that
      involved the left Psoas. It was drained 1800 cc of purulent fluid infected by
      Streptococo pneumoniae. RESULTS: In a CTA made 21 days after drainage, showed a
      very small residual collection. CONCLUSIONS: Primary Psoas Abscess are a very
      rare entity, with a low rate of mortatility if well treated.

PMID- 17175937
TI  - [Gunshot bladder trauma: case report and literature review].
AB  - OBJECTIVE: To report one case of gunshot bladder trauma and to review its
      diagnosis and treatment in the related literature. METHODS: We report the case of
      a 43-year-old-male with an abdominal firearm wound and gross haematuria. Imaging
      diagnosis by abdominal and pelvic CT and CT-cystography. Surgical treatment.
      RESULTS: CT-cystography showed extraperitoneal bladder rupture. Exploratory
      laparotomy to evaluate for other associated injuries. Bladder wall surgical
      closure and ureteroneocystostomy with transvesical technique because of complete
      distal ureter tear. Broad spectrum antibiotherapy. Favourable progress. The
      patient was discharged at 14th day. CONCLUSIONS: Firearm bladder traumas are a
      rare entity. Surgical exploration and closure is mandatory. In haemodynamicaly
      stable patients, abdomen and pelvis CT and CT-cystography allow us to rule out
      associated injuries and to classify the bladder trauma type. Ureteral damage
      associated in 5-8,9%, diagnosed during surgical exploration. Broad-spectrum
      antibiotherapy in all patients.

PMID- 17175938
TI  - [Maxillary sinus metastasis of renal cell carcinoma].
AB  - Paranasal sinuses and nose metastasis are very uncommon tumors, about 50 have
      been reported. Renal cell carcinoma is the primary neoplasm which most frequently
      metastasizes in the nasosinusal region, followed by breast and lung. Symptoms are
      unspecific, but the epistaxis constitutes the most common sign due to the
      significant vascularizations of the tumor. Prognosis is poor. The survival rate
      fluctuates between 15-30% at 5 years. Surgery is the elective treatment.

PMID- 17175939
TI  - [Ureteral iatrogenic ligature. Endoscopic resolution].
AB  - The iatrogenic trauma of ureter is a complication that appears according to the
      different series between the 0.05-30% from the abdominal or pelvic surgeries. It
      the same affects to both ureters, being the rare bilateral ureteral trauma. The
      most frequent location is in the lower ureter. Maybe this fact must to that that
      is the patron of ureter more related by viacinity to the structures or organs in
      wich surgery is made. The most frequent causes are the gynecological ones,
      followed of the surgery of colon and vascular surgery. The reconstruction
      techniques depend on the level of the injury. The maneuvers of support and the
      endourology treatment can be useful for the resolution of these injuries.

PMID- 17175940
TI  - [Side-effects in metastasis of penis. Succinct revision of Spanish urologic
      literature (period: 1980-2005)].

PMID- 17175941
TI  - [Penis and testicular shotgun injuries].

PMID- 17175942
TI  - [Complications of the surgery in the reassignment of sex].

PMID- 17175943
TI  - [Renal hydatidic cyst].

PMID- 17175944
TI  - ["Back table" in descapsulated kidney for transplant].

PMID- 17175945
TI  - [Role of prostatic stents and transurethral microwave thermotherapy in the
      treatment of voiding disorders related to benign prostatic hyperplasia (CTMH-AFU
      forum 2005)].
AB  - Prostatic stents and microwave thermotherapy are minimally invasive techniques
      for the treatment of voiding disorders related to benign prostatic hyperplasia. A
      review of the literature evaluates the place of these treatments in 2006.
      Permanent prostatic stenting is rarely used, but remains a treatment option for
      patients with obstructive disorders and a formal anaesthetic contraindication.
      Temporary stenting can be used to predict the effect of resection in selected
      patients. Finally, microwave thermotherapy, not widely used in France, has a
      promising clinical efficacy and occupies a place between medical treatment and
      surgery.

PMID- 17175946
TI  - [Role of endoscopy in the management of upper urinary tract tumors].
AB  - Transitional cell carcinomas of the upper urinary tract are rare tumours that
      represent about 5% of all transitional cell carcinomas. The reference treatment
      is currently open nephroureterectomy. Low-grade or superficial urinary tract
      tumours have a good prognosis, similar to that of noninvasive bladder tumours
      (80% 5-year specific survival). The surgical management of upper urinary tract
      tumours is gradually evolving towards complete preservation of the upper urinary
      tract and renal parenchyma, when compatible with local conditions. Conservative
      endoscopic treatments (ureteroscopy, percutaneous treatment) provide good
      oncological results and constitute a possible alternative to nephroureterectomy
      for the systematic management of good prognosis tumours. The cost of endoscopy
      equipment and consumable items is currently a limiting factor to the widespread
      use of these techniques.

PMID- 17175947
TI  - [Identification of lithogenic risk factors by a simplified first-line laboratory
      assessment in urinary calculi patients].
AB  - INTRODUCTION: A simplified first-line laboratory assessment is recommended by the
      Stones Committee of the Association Francaise d'Urologie (CLAFU) right from the
      first episode of renal stones to detect any lithogenic risk factors. This study
      was designed to evaluate the feasibility of this assessment in urology, to
      specify the frequency of risk factors and to compare the results between first
      stone formers and recurrent stone formers. MATERIAL AND METHODS: This prospective
      study included patients with a first stone or recurrent stones with no previous
      laboratory assessment. Known cases of secondary stones were excluded. The stone
      or fragments had to be analysed by infrared spectrophotometry. In addition to the
      usual assessment, the first-line laboratory assessment was performed two to three
      months after the acute episode with a blood test (calcium, phosphorus, uric acid
      and creatinine), 24-hour urine collection (volume, calcium, uric acid, urea,
      creatinine, sodium) and first morning urine sample (pH, density, crystals).
      RESULTS: The results are based on 115 of the 204 patients included (69 first
      stones, 46 recurrent stones). The assessment was performed and interpreted
      easily, except for collection of stone fragments. Infrared spectrophotometry was
      performed in only 49 patients. Whewellite was the most frequent crystalline
      structure. No patients presented hyperparathyroidism or renal failure. In 69% of
      cases, the urinary assessment identified one or several risk factors, with
      insufficient diuresis (42%), hypercalciuria (29%), hypernatriuria (41%), high
      urinary urea (29%), and hyperuricuria (20%). 25% of patients had a single
      abnormality, 20% had two abnormalities, the most frequent combination being
      hypercalciuria-hypernatriuria, and 11% had 4 or more abnormalities. Comparison of
      first stone formers and recurrent stone formers did not reveal any difference in
      the frequency of lithogenic risk factors. CONCLUSION: This easy to perform
      assessment identified lithogenic risk factors in many cases, in both first stone
      formers and recurrent stone formers, that can guide the prevention of recurrent
      stones.

PMID- 17175949
TI  - [Should frozen section examination be performed systematically as part of
      conservative surgery for renal cell carcinoma?].
AB  - OBJECTIVE: To prospectively assess the value of frozen section examination during
      conservative surgery for renal cell carcinoma (RCC) in exclusively elective
      indications and to evaluate the reality of safety margins. MATERIAL AND METHODS:
      From 1997 to 2001, 220 conservative procedures for RCC were performed in our
      department, including 104 elective lumpectomies, 61 of which were studied
      prospectively. The mean age of these 61 patients was 59.4 years (range: 34.2 to
      78.5). The mean tumour diameter was 32 mm (range: 12 to 50). Tumours were
      peripheral in 51 cases and in a juxtahilar position in 10 cases. Resection
      margins were evaluated macroscopically by the surgeon, and the specimen was
      systematically sent for frozen section examination. Incomplete margins, i.e.
      negative but with no safety margin, were distinguished from positive margins on
      the final histological examination. The thickness of the safety margins was
      measured on the cortical and deep extremities of the operative specimen. The mean
      follow-up was 78.5 months (range: 52 to 101). RESULTS: Histological types of RCC
      comprised conventional clear cell (n = 42), tubulopapillary (n = 17) and
      chromophobe (n = 2), stage pT1 (n = 57) and pT2 (n = 4), and grade 1 (n = 16), 2
      (n = 35) and 3 (n = 10). No positive margins were detected. The mean thickness of
      the safety margin was 7 mm peripherally and 2 mm in depth with no correlation
      between these two values. Surgeons concluded on the presence of 51 complete
      margins and 10 incomplete margins versus 53 and 8 on histological examination,
      respectively. Frozen section examination never modified the course of the
      operation. All patients were alive and recurrence free at last follow-up.
      CONCLUSION: Macroscopic evaluation of resection margins by the surgeon is precise
      and usually avoids the need for frozen section. However when the margins are
      considered to be incomplete by the surgeon, frozen section examination is
      mandatory to avoid positive margins, which must remain the main objective of
      conservative surgery.

PMID- 17175948
TI  - [Laparoscopic partial nephrectomy: A series of 17 cases].
AB  - OBJECTIVE: The objective of this study was to evaluate the Feasibility, the
      morbidity and the carcinologic results of laparoscopic partial nephrectomy.
      MATERIAL AND METHODS: Between August 2001 and December 2005, 17 partial
      nephrectomies were performed by laparoscopy in patients with a mean age of 59.2
      years. Postoperative complications, the conversion rate, operating time, arterial
      clamping time, length of hospital stay and oncological results were studied for
      each patient. RESULTS: The mean operating time was 190 min, the mean arterial
      clamping time was 30 min and the mean hospital stay was 6.3 days. There were 2
      complications including one postoperative haematoma requiring surgical revision
      for drainage and repositioning of a stent for urine leak. Two conversions had to
      be performed early in our experience. A tumour recurrence 2 years after the
      initial operation was treated by total nephrectomy. CONCLUSION: Our results in
      terms of morbidity are similar to those reported for open surgery, but the
      recurrence rate appears to be slightly higher than that observed with open
      partial nephrectomy. Laparoscopic partial nephrectomy remains a difficult
      operation requiring a learning curve even for a department that regularly
      performs laparoscopic surgery.

PMID- 17175950
TI  - [Vascular prostheses and renal transplantation].
AB  - OBJECTIVE: To evaluate the complications, the morbidity and mortality of renal
      transplantation in patients with a vascular prosthesis inserted either prior to
      or at the same time as renal transplantation. PATIENTS AND METHOD: Between
      January 2001 and January 2006, six renal transplantations were performed in
      patients with arterial vascular prostheses or requiring concomitant insertion of
      a vascular prosthesis during renal transplantation. The mean age was 58 years
      [range: 47-69 years]. In each case, we evaluated operative difficulties,
      complications and postoperative course (morbidity, mortality) and the renal
      functional result. RESULTS: The mean operating time was 230 minutes [range: 130
      380 minutes] with a mean blood loss of 390 ml [175-750 ml]. Three patients
      required another surgical operation for femoral thrombosis, iliofemoral
      thrombosis and compressive haematoma. The median length of hospital stay was 21
      days [range: 9-78 days]. Graft function was restored immediately in all six
      patients, and one case of graft loss was observed. The morbidity was higher than
      that usually observed after renal transplantation. With a mean follow-up of 26
      months, the vascular and renal results are satisfactory. CONCLUSION: Renal
      transplantation in patients with a history of vascular prosthesis or requiring
      replacement of the vascular prosthesis at the same time as renal transplantation
      can be performed with satisfactory results but with an increased morbidity. The
      vascular treatment must be part of a multidisciplinary strategy in the context of
      transplantation.

PMID- 17175951
TI  - [Practice patterns of general practitioners in the Loire-Atlantique region and
      their patients' knowledge of prostate cancer screening].
AB  - OBJECTIVE: The objective of this study was to analyse the practices of general
      practitioners in the Loire-Atlantique region and their patients' knowledge about
      prostate cancer screening. MATERIAL AND METHODS: A "doctor" questionnaire
      focussing on prostate cancer screening practices was sent by mail to 1,086
      general practitioners of the Loire-Atlantique region. "Patient" questionnaires
      were enclosed to be completed by 5 consecutive male patients over the age of 50.
      RESULTS: The doctor participation rate was 4.7%. Prostate cancer screening was
      performed by 98% of doctors. However 63% of doctors performed digital rectal
      examination and PSA annually, but only 27% in the specific age-group from 50 to
      75 years. The "patient" questionnaire was completed in 233 cases. 88% of patients
      were informed about prostate cancer screening, essentially by their doctor or the
      media. 33% of patients indicated digital rectal examination and 23% indicated PSA
      as prostate cancer screening methods. Only 33% of patients declared to know one
      of the treatments for prostate cancer, reporting surgery in 78% of cases and
      radiotherapy in 32% of cases. CONCLUSION: General practitioners answering the
      questionnaire performed prostate cancer screening, but according to AFU
      guidelines only in 1/3 of cases. The majority of patients considered that they
      had been informed about prostate cancer screening, but with many imperfections.

PMID- 17175952
TI  - [Does transrectal MRI before radical prostatectomy modify the operative technique
      to decrease the positive margin rate?].
AB  - OBJECTIVE: To determine the value of magnetic resonance imaging (MRI) in the
      surgical management of prostate cancer patients. PATIENTS AND METHODS: 159
      patients with prostate cancer underwent transrectal MRI before retropubic radical
      prostatectomy (RP). Patients operated despite a suspicion of extraprostatic
      extension on MRI had a modified non-nerve-sparing surgical technique.
      Postoperative histological findings were compared to MRI data. RESULTS: 34/159
      patients (21.4%) had suspected extraprostatic extension in MRI. The pT3 rate on
      the RP specimen was significantly higher for patients with abnormal MRI than for
      patients with normal MRI (61% versus 39%, p = 0.02). Among pT3 patients, the
      positive surgical margin rate was significantly lower in the group with abnormal
      MRI than in the group with normal MRI (24% versus 51%, p = 0.035). CONCLUSIONS:
      Among patients with stage pT3 on the RP specimen, those in whom extraprostatic
      extension was suspected on MRI were treated by a modified surgical technique
      resulting in a lower positive surgical margin rate.

PMID- 17175953
TI  - [The role of the IPSS (International Prostate Symptoms Score) to evaluate the
      frequency of disability induced by each of the 7 symptoms. (CTMH-AFU study)].
AB  - INTRODUCTION: Evaluation of a patient with voiding disorders related to benign
      prostatic hyperplasia is theoretically performed by means of the IPSS score,
      which comprises only one global quality of life question. This study used a
      questionnaire to evaluate the frequency of disability induced by each of the
      symptoms of the IPSS in a representative sample of the French population and then
      proposed a weighting of the IPSS score by the statistical weight of disability of
      each symptom without having to increase the number of questions. METHODS: A
      survey on the voiding behaviour of French men was performed by TNS Sofres
      Healthcare by questionnaire between 18/4/03 and 27/5/03 in a panel of 3877 men
      aged 50 to 80 years representative of the French population. This survey
      comprised demographic and sociological questions as well as the IPSS score. A
      specific question concerning the disability induced by each of the 7 symptoms
      ("Does it bother you enormously, a lot, slightly, not at all? ") was added.
      RESULTS: Each symptom induced a different type of disability: the most marked
      disability was induced by urgent micturition and uri nary frequency, while
      interrupted stream only had a minor impact. Statistical modelling was performed
      to obtain a coefficient for each level of frequency of the symptom, directly
      integrating the theoretical statistical weight of the specific disability. With
      this statistical method, the frequency of each of the 7 symptoms was weighted by
      a coefficient from 0.00 to 1.54 according to the disorder and its frequency. A
      total of 35 coefficients were necessary to construct the score as a function of
      the frequencies of disability of the 7 symptoms. This method was used to classify
      disorders according to the degree of disability that they induced, the most
      disabling being urgency (from 0 to 1.54), followed by straining to urinate (0 to
      1.17), and then each of the other 5 symptoms. CONCLUSION: The original feature of
      this new score is that it directly integrates the frequency and theoretical
      specific disability of each of the 7 symptoms of the IPSS score. However, it
      needs to be validated by a prospective clinical trial.

PMID- 17175954
TI  - [Lower urinary tract symptoms are poorly correlated with erectile dysfunction].
AB  - OBJECTIVE: To estimate the correlation between the frequency of lower urinary
      tract symptoms (LUTS) associated with BPH and the quality of the patient's
      sexuality. METHODS: The IPSS IIEF BSIA and SPI questionnaires were proposed to
      930 patients with voiding disorders. Correlation coefficients between these
      scores were determined on inclusion and after 18 and 36 months of follow-up.
      RESULTS: Poor correlations were demonstrated between the IPSS and IIEF scores.
      Correlations of the variations of these scores confirmed the low degree of
      dependence between IPSS and IIEF Adjustment for age had little impact on this
      relationship. CONCLUSION: LUTS are not a major predictive factor of the patient's
      sexuality and prognosis. However in view of the frequency of sexual disorders in
      this age-group, it is to evaluate the impact of treatments of BPH on the
      patient's sexuality.

PMID- 17175955
TI  - [Mitrofanoff continent urinary diversions: The opinion of 57 patients].
AB  - OBJECTIVE: To evaluate the psychological repercussions and degree of adaptation
      in daily living of patients with a Mitrofanoff continent external urinary
      diversion. PATIENTS AND METHOD: Fifty seven patients were questioned about their
      Mitrofanoff continent urinary diversions, using a questionnaire translated into
      their spoken language (Arabic). RESULTS: The mean age was 29 years (range: 10 to
      72 years). The indication for the diversion was a neurological cause in 91% of
      cases. Continence was achieved in every case, but after surgical revision in 3
      cases. Self-catheterization was considered to be easy and not especially
      bothersome in 49 cases (86%). The diversion had occasional and moderate
      repercussions on activities of daily living, estimated between 3.5 and 17.5%.
      Sixteen patients (94%) returned to work and another fifteen (79%) successfully
      resumed their schooling. Nineteen patients (83%) who were sexually active
      preoperatively reported a satisfactory sex life after the operation. Finally,
      this operation was highly appreciated by the patients in 96.5% of cases for
      hygienic and psychological reasons. CONCLUSION: The Mitrofanoff urinary diversion
      allows satisfactory social, work and family rehabilitation provided the patient
      adapts to diversion management.

PMID- 17175956
TI  - [Chemical destruction of sacral nerve roots by alcohol injection for the
      treatment of overactive bladder].
AB  - INTRODUCTION: This study retrospectively reviewed the value of alcohol injection
      of sacral nerve roots after a lidocaine test in two indications: detrusor
      instability-detrusor hyperactivity syndrome and cystalgia. MATERIAL AND METHODS:
      Single-centre retrospective study from January 1992 to March 2003. Twenty-eight
      patients (1 man, 27 women) were admitted to the urology department for lidocaine
      test injection because of detrusor hyperactivity 24 cases (idiopathic = 13,
      neurological = 11), and cystalgia in another 4 cases. RESULTS: After the
      lidocaine test, infiltration of the sacral nerve roots (bilateral S3) by 70%
      alcohol was performed in 24/28 cases. The therapeutic effect was assessed at 1
      month: 14 out of 24 patients reported that they were globally improved by the
      alcohol injection. The mean duration of the therapeutic effect was 3.8 months. In
      the longer term, only one of the 14 patients initially improved did not
      subsequently experience deterioration of the clinical features (with a follow-up
      of 8 months). A second alcohol injection was performed in 5/28 patients, with a
      positive result in only one case (4%). COMPLICATIONS: 6/24 (25%) patients
      developed lower limb pain that resolved over 2 to 3 months; 3/24 (12%) presented
      immediate postoperative urinary retention (that persisted in the long term in 1
      case); 1/24 (4%) presented cicatricial anal incontinence. CONCLUSION: Alcohol
      injection of sacral nerve roots is a simple and inexpensive technique, but is
      associated with morbidity, and has inconstant and only transient effects. It can
      only be considered exceptionally in highly selected cases when no more effective
      treatments are available, such as botulinum toxin injection or sacral nerve root
      neuromodulation.

PMID- 17175957
TI  - [Ureteric and bladder involvement of deep pelvic endometriosis. Value of
      multidisciplinary surgical management].
AB  - OBJECTIVES: To evaluate the clinical features, staging by medical imaging,
      treatment strategy and results of surgical management of deep pelvic
      endometriosis with bladder and/or ureteric involvement. MATERIALS AND METHODS:
      Eighteen cases of ureteric and/or bladder deep pelvic endometriosis (DPE) were
      treated in our centre between 1996 and 2004. Preoperative data (clinical
      symptoms, MR imaging), intraoperative data (resection and urinary tract diversion
      procedures, associated procedures on the genital and gastrointestinal tracts),
      and postoperative data (histological results, complications, anatomical follow-up
      by imaging and functional assessment) were reviewed. RESULTS: Urinary symptoms
      were present in 55% of cases, genital symptoms were present in 83% of cases and
      gastrointestinal symptoms were present in 46% of cases. A combination of
      gynaecological and gastrointestinal lesions was demonstrated on imaging in 82% of
      cases. The mean postoperative follow-up was 16 months (range: 6-36 months). Six
      patients presented anterior vesical endometriosis. In these cases, the
      sensitivity and specificity of MRI were 100%. Six partial cystectomies were
      performed. All corresponded to endometriotic lesions on histological examination.
      No cases of recurrence of vesical endometriosis were observed. Posterior
      endometriosis with ureteric involvement was observed in 13 patients (including
      one with vesical endometriosis). The ureteric lesion was asymptomatic in 8 out of
      13 cases (61%). The diagnostic sensitivity of MRI was 92% for posterior nodules,
      identifying 4 lateral parametrial nodules and 8 median retrocervical nodules.
      Ureterohydronephrosis was observed in 3 patients with lateral parametrial nodules
      and 8 patients with median retrocervical nodules, and was bilateral for 3
      patients, i.e. 14 dilated renal units. Surgical management consisted of 2
      ureteric resections with end-to-end anastomosis, 3 psoas bladder reimplantations,
      and 9 ureterolyses (8 patients). Two out of 13 patients (15%) with ureteric
      lesions treated by ureterolysis developed recurrence of the ureteric stricture
      with upper tract dilatation related to recurrence of the lateral nodule. In 14
      patients, genital and/or gastrointestinal resections were associated with the
      urinary tract procedure. CONCLUSION: Preoperative evaluation of all DPE lesions
      is based on MRI with reconstruction images of the ureter in the presence of
      urinary tract lesions. Systematic ureteric stenting prior to surgical dissection
      of the pelvic wall is recommended in patients with posterior nodules and in the
      case of partial cystectomy for anterior nodules when the ureteric meati are
      adjacent to the lesion. Ureteric reimplantation onto a psoas hitch bladder must
      be performed when the DPE lesions are extensive and partly resected or invade the
      ureteric wall. The frequency of associated lesions (urinary, gynaecological
      gastrointestinal) justifies a multidisciplinary surgical approach.

PMID- 17175958
TI  - [Extracorporeal lithotripsy of upper urinary tract stones in children].
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy of
      extracorporeal lithotripsy for the treatment of urinary stones in children.
      MATERIAL AND METHODS: From November 2002 to November 2004, 34 children from the
      department of paediatric urology of Rabat children's hospital, aged 3 to 15 years
      (mean age: 6 years), including 15 children under the age of 6 years, were treated
      for symptomatic urinary stones in the extracorporeal lithotripsy centre with a
      Lithostar Multiline lithotriptor adapted to the treatment of adults as well as
      children, even very young children. At the time of treatment, all 34 children had
      normal blood pressure, normal blood urea and creatinine, normal clotting
      parameters, sterile urine and no urinary tract obstruction. All children under
      the age of 6 years were treated under ketamine sedation. RESULTS: Treatment
      required a variable number of sessions from 1 to 3 (mean: 1.5) and concerned 38
      stones: 30 renal stones including 6 staghorn and 8 ureteric stones. The number of
      impacts delivered per session ranged from 1,500 to 3,500 for renal stones (mean:
      2,500 impacts), with a maximum of 5,000 impacts for ureteric stones (mean: 3,250
      impacts). Three months after the last lithotripsy session, 30 patients presented
      no fragments. No lesion of the treated kidney or adjacent organs was demonstrated
      on follow-up ultrasound performed 3 to 6 months after treatment. CONCLUSION:
      Evaluation of the results confirms the efficacy of extracorporeal lithotripsy for
      the treatment of even very large urinary stones in children, even in very young
      children. Extracorporeal lithotripsy is now the first-line treatment for-urinary
      stones in children.

PMID- 17175959
TI  - [Uroflowmetry in children: Prospective study of normal parameters].
AB  - INTRODUCTION: Uroflowmetry is the simplest urodynamic test to study the lower
      urinary tract. Uroflowmetry parameters, especially maximum flow rate, are
      important, but are difficult to interpret due to the lack of normal uroflowmetry
      data in children. OBJECTIVE: The objective of this prospective clinical study was
      to evaluate normal uroflowmetry parameters in a prospective series of 202
      children between the ages of 5 and 15 years. MATERIALS AND METHODS: We
      prospectively studied uroflowmetry in a series of 202 children between the ages
      of 5 and 15 years. Children with voiding disorders, or a psychiatric or
      neurological illness were excluded. The following variables were determined: age,
      body surface area (BSA (m2)), maximum flow rate (Qmax (ml/s)), voided volume (V
      (ml)) and maximum flow time (TQmax (s)). RESULTS: Qmax increased with age, V and
      BSA in both sexes and was greater in girls. In girls between the ages of 5 and 6
      years, mean Qmax was 15.8 for a mean V of 173 and BSA less than 1.06 and, in
      girls between the ages of 13 and 15 years, mean Qmax was 26.2 for a mean V of 327
      and BSA greater than 1.06. TQmax also increased with age, V and BSA and was
      greater in boys. In boys between the ages of 5 and 6 years, mean TQmax was 6.5
      for a mean V of 174 and BSA less than 1.6 and, in boys between the ages of 13 and
      15 years, mean TQmax was 7.4 for a mean V of 332 and BSA greater than 1.6. A
      positive correlation was demonstrated between age and uroflowmetry parameters and
      the most significant correlation was observed between age and Qmax in both sexes.
      CONCLUSION: This study on normal uroflowmetry parameters in children not
      presenting any voiding disorders demonstrated a significant difference, in both
      sexes, between Qmax and TQmax in relation to age, V and BSA. Uroflowmetry could
      therefore be useful in the diagnosis of infravesical obstruction.

PMID- 17175960
TI  - [Biphosphonates and osteonecrosis].

PMID- 17175961
TI  - [Secondary appearance of a carcinoma in an excluded native bladder: Report of
      three cases].
AB  - INTRODUCTION: The management of congenital urological malformations is sometimes
      complex and may require urinary diversion. Cystectomy is usually performed, but
      sometimes the bladder is left in place due to the presence of a pelvic cloaca and
      the morbidity related to this type of surgery. MATERIAL: The authors report three
      cases of patients treated by urinary diversion for a congenital malformation
      without primary resection of the bladder RESULTS: In the absence of any
      infectious complications, bladder carcinoma on an excluded native bladder was
      diagnosed at the age of 3 years, 4 years and 38 years, respectively. Histological
      examination showed transitional cell carcinoma in two cases and gastrointestinal
      type adenocarcinoma of the bladder in 1 case. CONCLUSION: The risk of secondary
      development of carcinoma in an excluded bladder during management of (congenital
      urological malformations is not negligible. Primary cystectomy therefore appears
      to be preferable. In the presence of a pelvic cloaca making this surgical
      resection unreasonable, it appears important to exclude the formation of a
      pyocyst by annual abdominal ultrasound. The authors also recommend cystoscopy and
      urine cytology with lavage to detect degeneration of the bladder mucosa.

PMID- 17175962
TI  - [Micropapillary bladder carcinoma].
AB  - Micropapillary bladder carcinoma is a recently described, rare variant of
      urothelial carcinoma reputed for its poor prognosis. The authors report the case
      of a 59-year-old man with invasive bladder tumour presenting with haematuria.
      Histological examination of resection chips revealed the typical histological
      features of high nuclear grade micropapillary carcinoma with invasion of the
      musculosa and the presence of numerous endolymphatic emboli. The authors discuss
      the clinicopathological and pathogenic features, treatment and clinical course of
      this tumour.

PMID- 17175963
TI  - [Primary large-cell neuro-endocrine carcinoma of the bladder].
AB  - Primary large-cell neuro-endocrine carcinoma of the bladder is a rare aggressive
      tumour with a very poor prognosis. The authors report the case of 78-year-old
      male patient with primary large-cell neuro-endocrine carcinoma of the bladder and
      discuss the pathological and therapeutic aspects of this tumour in the light of a
      review of the literature.

PMID- 17175964
TI  - [Prostatic sarcoma: Report of two cases].
AB  - Prostatic sarcomas are very rare tumours with a very poor prognosis. They may
      coexist with prostatic adenocarcinoma, in which case they are only diagnosed on
      histological examination of the operative specimen with identification of sarcoma
      on immunohistochemical analysis. Due to their rapidly invasive potential, they
      must be detect early in the course, particularly in young subjects. Certain
      clinical signs, such as obstructive urinary symptoms in a young man or rectal
      symptoms in an elderly man are suggestive of sarcoma. In this article, the
      authors report two cases of prostatic sarcoma surgically treated and present a
      review of the literature on this disease.

PMID- 17175966
TI  - [Laparoscopic treatment of an isolated ureteropelvic junction disruption
      following blunt abdominal trauma].
AB  - Isolated disruption of the ureteropelvic junction following blunt abdominal
      trauma is rare, although not exceptional. The diagnosis may be delayed. CT-scan
      with excretory phase imaging is the usual mode of diagnosis. The urinary tract
      can be repaired by an ureteropyelic anastomosis over a stent. The authors report
      the first case of an isolated disruption of the ureteropelvic junction following
      blunt abdominal trauma repaired by retroperitoneal laparoscopy.

PMID- 17175965
TI  - [Role of deep seminal tract imaging in the diagnosis of unilateral agenesis of
      the vas deferens. Case report of a patient with CFTR gene mutation].
AB  - The authors report the cases of a 35-year-old man with a 4-year history of
      primary infertility with normal clinical examination and semen parameters. Deep
      genital tract imaging demonstrated isolated unilateral agenesis of the pelvic
      portion of the left vas deferens associated with abnormalities of the homolateral
      seminal vesicle. Molecular analysis of the CFTR gene demonstrated composite
      heterozygosity with the presence of DeltaF508 / V938G mutations. In the light of
      this case, the authors recommend urogenital imaging for all men consulting for
      infertility.

PMID- 17175967
TI  - [Treatment of incarceration of the penis and scrotum].
AB  - The authors report a case of incarceration of the external genital organs by a
      metal ring, treated by section of this ring.

PMID- 17175968
TI  - [Adenosine deaminase activity in tuberculous and malignant pleural effusions].
AB  - Measurement of pleural adenosine deaminase activity (ADA) is a useful diagnostic
      tool for tuberculous pleurisy, but false-positive findings from non-tuberculous
      effusions have been reported. In order to improve diagnostic value of ADA it is
      recommended to estimate activity of both ADA1 and ADA2 izoenzymes or 2'
      deoxyadenosine/adenosine activity ratio. In order to evaluate ADA as a diagnostic
      parameter total ADA, with adenosine as a substrate, and 2'
      deoxyadenosine/adenosine activity ratio were measured in tuberculous and
      malignant pleural effusions. Altogether, 26 pleural exudates (11 tuberculous and
      15 malignant) were selected. ADA either with adenosine or 2'-deoxyadenosine was
      determined by colorimetric method of Giusti. Each pleural fluid sample was
      diluted prior to the assay (1:8) to avoid enzyme inhibition which was observed in
      nondiluted pleural effusions. The ADA level reached the diagnostic cut-off set
      for tuberculous effusions (40 U/L) in every 11 tuberculous exudates with the mean
      value of 85,3+/-47,1 U/L; in 9 of these the 2'-deoxyadenosine/adenosine ratio was
      less than 0,45. In the malignant group of patients, no one ADA level exceed 40
      U/L, being estimated at 10,6+/-7,7 U/L (p<0,001). In 10 of these 15 exudates the
      2'-deoxyadenosine/adenosine ratio was undetectable, in four it was less than 0,45
      and only in one it was over 0,45. We concluded that ADA measured by the Giusti
      method proceeded by the dilution 1:8 of the pleural effusion samples very good
      differentiates tuberculous from malignant pleurisy, without the necessity to
      determine the 2'-deoxyadenosine/adenosine ratio. The investigation needs to be
      continued on the more numerous groups of patients.

PMID- 17175969
TI  - [Diagnostic utility of pleural fluid eosinophilia].
AB  - Diagnostic utility of eosinophilic pleural effusion (EPE) is still the matter of
      controversy. Some earlier studies have showed that pleural fluid eosinophilia
      considerably reduces the probability of malignancy, while some later analyses
      were not able to confirm such an observation. To evaluate the diagnostic
      significance of EPE the retrospective study of all patients with pleural effusion
      (PE) managed in our hospital between 1995 and 2001 has been undertaken. We
      analyzed 915 patients with PE and 1086 pleural effusions subjected to a
      biochemical, cytological and bacteriological examinations. We identified 72
      (7,9%) patients with EPE and 82 EPEs liquid (7,5%) among them. The group of
      patients with EPE consisted of 41 (57%) males and 31 (43%) females; average age
      62.2 year (range 21.0-94.0). Etiologic distribution showed the largest subgroup
      were patients with malignant EPE (n=28, 38.9%) followed by idiopathic EPE (n=12,
      16.7%) and parapneumonic EPE (n=11, 15.3%). Looking for predictors of malignancy
      in EPE we found some differences between malignant and nonmalignant EPE: patients
      with malignant EPE were older (67.9+/-13.6) then patients with nonmalignant EPE
      (58.7+/-15.6; p<0.015), and have higher percentage of lymphocytes in PE (47.9+/
      16.9 vs. 37.9+/-18.9; p<0.03). Similarly we noticed some differences between two
      largest groups (malignant and idiopathic PE). Patients with malignant PE were
      older (67.9+/-13.6 vs. 53.9+/-13.6 yrs; p=0.005), had lower pleural fluid
      eosinophilia (25.2+/-15.3% vs. 41.4+/-21.0%; p=0.01) and higher percentage of
      lymphocyte in PE (47.9+/-16.9 vs. 29.6+/-19.1%; p=0.004). We conclude that
      pleural fluid eosinophilia cannot be considered as predictor of nonmalignant
      etiology. The older age and the higher number of lymphocytes in EPE might suggest
      malignant etiology of pleural effusion.

PMID- 17175970
TI  - [The role of fiberoptic bronchoscopy in the diagnostic algorithm of solitary
      pulmonary nodule].
AB  - The role of fiberoptic bronchoscopy in the diagnosis of peripheral lung nodule is
      controversial. The aim of the study was to evaluate the results of routine
      bronchoscopy performed in patients with peripheral lung nodule of 5-40 mm in
      diameter. From 60 patients with peripheral lung nodule, who underwent routine
      diagnostic fiberoptic bronchoscopy between 2003 - 2005, we selected 36 patients
      in whom the final discrimination between malignant and benign tumor was achieved
      based on either pathological examination or radiological criteria (lack of growth
      within 2 years of radiological follow up). There were 22 (61%) patients with
      malignant tumor and 14 (39%) with benign nodule. All malignant tumors were lung
      carcinomas. In 10 of these patients we found macroscopic abnormalities during
      bronchoscopy and in 9 of them pathologic examination of specimens collected
      during the procedure could confirm malignant tissue. In two patients with benign
      lung nodule a second lung lesion (in different lung lobe) which proved to be lung
      cancer was identified during fiberoptic bronchoscopy. Sensitivity, specificity
      and diagnostic accuracy of fiberoptic bronchoscopy in the diagnosis of peripheral
      lung nodules were 41%, 100%, and 64% respectively. Abandoning fiberoptic
      bronchoscopy in the diagnostic algorithm in patients with peripheral lung nodules
      seems unjustified, although its limitations should be taken into account.

PMID- 17175971
TI  - [Exhaled nitric oxide in patients with obstructive sleep apnea syndrome].
AB  - Exhaled nitric oxide has been extensively investigated as a non-invasive marker
      of airway inflammation. Some authors have suggested that morning FE(NO) in
      obstructive sleep apnea syndrome (OSAS) patients is elevated due to inflammation
      of upper airways, while others have not found any differences between patients
      and healthy subjects. The purpose of this study was to analyze concentration of
      exhaled nitric oxide (FE(NO)) in OSAS patients. METHODS: 119 (99 M, 20 F)
      consecutive patients of sleep laboratory participated in this study. Standard
      overnight sleep studies with polysomnography or portable screening device were
      carried out in the whole group: OSAS was diagnosed in 66 patients and 53 no-OSAS
      served as controls. FE(NO) was measured on-line with a flow rate kept at 0.045 -
      0.055 l/s, according to the recommendations of ATS using a chemiluminescence
      analyzer twice: before the sleep study (8-10 p.m.) and after termination of data
      collection (6 - 8 a.m.). There were no differences in age between patients and
      controls. Respiratory disturbance index (RDI) was 40.3+/-24.9 in patients and
      3.7+/-2.8 in controls (p<0.001). In OSAS patients both evening and morning FE(NO)
      was significantly higher compared to controls (23.1+/-14.8 ppb vs. 16.8+/-9.8 ppb
      and 22.4+/-13.2 ppb vs. 15.3+/-8.1 ppb respectively, p<0.05). Weak but
      statistically significant correlations for the whole group between morning FE(NO)
      and mean and minimum arterial oxygen saturation (SaO2) during sleep and number of
      study minutes with SaO2<90% were observed. Lower evening FE(NO) in OSAS patients
      with coexisting arterial hypertension when compared to normotensive OSAS patients
      was also noticed (19.1+/-10.8 ppb vs. 27.1+/-19.1 ppb; p<0.05). CONCLUSIONS: The
      increase in FE(NO) in OSAS patents may be caused by repetitive apneas and
      hypoxemia during sleep.

PMID- 17175972
TI  - [Influence of bronchoscopy on nitric oxide in exhaled air].
AB  - Nitric oxide has been extensively studied as a noninvasive marker of airway
      inflammation, especially in asthma. Assuming, bronchoscopy can produced not only
      systemic but also local inflammatory response we hypothesized that
      bronchofiberoscopy can be responsible for an increase in nitric oxide synthesis
      with resulting increase in fractional concentration of exhaled nitric oxide
      (FE(NO)). Seventeen subjects (10 M, 7 F), at mean age of 53.8+/-14.1 yrs
      undergoing diagnostic bronchoscopy participated in the study. The indications for
      bronchoscopy were as follows: lung cancer (n=5; 29%), interstitial lung diseases
      (n=3; 18%), slowly resolving pneumonia (n=3; 18%), hemoptysis (n=3; 18%),
      differential diagnosis of asthma/ dyspnea (n=3; 18%). During bronchoscopy
      bronchial washing (n=7) and bronchoalveolar lavage (BAL) (n=10) has been
      performed. FE(NO) has been analyzed on-line with chemiluminescence analyzer
      (NIOX, Aerocrine, Sweden) according to American Thoracic Society guidelines,
      before and at 1, 2, 3 and 24 hours after bronchoscopy. Mean FE(NO) before
      bronchoscopy was 19.7+/-4.5 ppb (mean +/- SEM), post - bronchoscopy a decrease
      with a nadir at second hour (12.1+/-1.5 ppb, p<0.05) was observed, FE(NO) 24
      hours after bronchoscopy was not different than baseline (18.4+/-2.5 ppb). There
      were no differences in the FE(NO) profile in BAL patients when compared to those
      in whom only the bronchial washing has been performed. CONCLUSIONS: Bronchoscopy
      leads to a significant decrease in exhaled nitric oxide. The underlying
      mechanisms are unclear. Future studies including analysis of other inflammatory
      markers are needed to explain these changes.

PMID- 17175973
TI  - [Holter ECG monitoring during research bronchofiberoscopy in patients with
      asthma].
AB  - Bronchoscopy is a very useful tool in asthma research studies. The study was
      undertaken to evaluate the effect of bronchoscopy, BAL and bronchial biopsies on
      heart rate and arrhytmias in patients with asthma. Twenty patients (12 M, 8 F,
      mean age 39,6+/-16,3 yrs) with asthma (mean FEV, 81+/-19.5% pred.; mean FEV(1)%VC
      69+/-12.3%) participated in the study. Holter ECG monitoring was performed twice:
      before (1 or 2 days) and on the day of bronchoscopy. Heart rate and cardiac
      arrhythmias were compared to prebronchoscopy recording at four separate time
      intervals: during bronchoscopy, first postbronchoscopic hour, second
      postbronchoscopic hour and total 24 hours. There were no significant differences
      between mean heart rate at the time of bronchoscopy (88.5+/-14.1 min(-1) vs
      83.7+/-11.9 min(-1)), first and second postbronchoscopic hour (80.9+/-15.8 min(
      1) vs 85.7+/-13.7 min(-1) and 82.6+/-13.6 min(-1) vs 80.6+/-11.6 min(-1)) as well
      as total 24 hours (76.1+/-11.2 min(-1) vs 75.9+/-9.4 min(-1)) as compared to
      prebronchoscopic recordings. Max. heart rate during bronchoscopy was higher as
      compared to the corresponding time of prebronchoscopic recording (134.5+/-11.5
      min(-1) vs 122.5+/-19.6 min(-1), p<0,05). No differences in the number and type
      of ventricular (VA) and supraventricular arrhythmias (SVA) between the pre- and
      peribronchoscopic monitoring were observed. Positive correlation between the age
      and the number of VA during bronchoscopy has been found. CONCLUSION:
      Bronchoscopic procedures in asthma patients do not increase the risk of cardiac
      arrhythmias. Some factors influencing the heart rate and number of VA during
      bronchoscopy can be identified.

PMID- 17175974
TI  - [Influence of nasal continuous positive airway pressure on response to exercise
      in patients with obstructive sleep apnea syndrome].
AB  - Obstructive sleep apnea syndrome (OSAS) patients are at risk of cardiovascular
      complications. The aim of this study was to assess the effect of treatment with
      continuous positive airway pressure (CPAP) on the response to symptom limited
      exercise test. METHODS: twenty nine OSAS patients (1 F, 28 M), mean age 50.7+/
      9.7 yrs with body mass index of 32.6+/-4.5 kg/m2 participated in the study. OSAS
      was diagnosed by overnight polysomnography. Incremental cardiopulmonary exercise
      test (CPET) on a treadmill was performed twice: before and after 2-3 weeks of
      regular treatment with CPAP. RESULTS: mean apnea + hypopnea index (AHI) before
      therapy was 57.6+/-12 h(-1). CPAP treatment did not change peak oxygen
      consumption (VO2max) (38.3+/-9.0 vs. 38.9+/-6.9 mlO2/kg/min, p=ns) or peak heart
      rate (153.4+/-21 min- vs. 155.5+/-22 min(-1), p=ns). There were no significant
      changes in ventilation or gas exchange variables. However, a decrease in peak
      systolic blood pressure from 194.5+/-24 mmHg to 186.7+/-27.9 mmHg (p<0.05) with
      CPAP treatment was found. During recovery a decrease in heart rate (at 1st minute
      and minutes 3 - 6) and mean arterial pressure (MAP) (minutes 4-7) with CPAP
      treatment was observed. Significant correlations between VO2max and AHI (r=-0,38,
      p<0,05); MAP at peak exercise and: AHI, mean oxygen saturation (SaO2) during
      sleep, minutes of sleep with SaO2<90% (T90); MAP at recovery (minutes 3-8) and
      T90 before CPAP treatment were also noted. CONCLUSIONS: OSAS patients are not
      limited on exercise. Treatment with nasal CPAP attenuates circulatory response to
      incremental exercise on a treadmill.

PMID- 17175975
TI  - [Factors determining the decision to initiate nCPAP therapy in patients with
      obstructive sleep apnea (OSA)].
AB  - The aim of the study was to determine the factors which influence the decision to
      initiate nCPAP therapy in patients with OSA. 184 patients with OSA were enrolled
      to the study. They were divided into two groups: group "T" ("treated") which
      consisted of 112 patients who were being treated with nCPAP and group "R"
      (resigned") which consisted of 68 patients who refused nCPAP therapy. The main
      causes of their refusal were: the possibility of surgical treatment, nCPAP
      intolerance and high costs associated with the purchase of a nCPAP device. The
      mean age of the patients was comparable in both groups (49.2 +/- 8.7 vs 50.5 +/-
      10.6 yrs). Patients from group T had a significantly higher body weight and BMI
      than the patients from group R (106.6 +/- 2.1 kg vs 94.1 +/- 20.9 kg, p < 0.0001
      and 35.0 +/- 6.3 kg/m2 vs 31.1 +/- 6.3 kg/m2, p < 0.00005 respectively). The
      patient evaluation included physical examination, a questionnaire concerning
      symptoms related with OSA and OSA assessment by poly-MESAM, polysomnography (PSG)
      before and with nCPAP trial therapy. RESULTS: the following parameters obtained
      in the poly-MESAM recording differed significantly (p < 0.001) between group T
      and group R: RDI (54.6 vs 41.7), HRV index (24 vs 11), SaO2 min (67.0 vs 75% and
      SaO2 mean (84 vs 88%). Analysis of the baseline PSG did not reveal differences in
      sleep structure in both groups. We found a significantly higher AHI in group T
      (63.6 vs 44.9, p < 0.00005). PSG confirmed a significantly lower SaO2 min and
      SaO2 mean in group T (67.0 vs 75.0%, p < 0.001 and 89.0 vs 92%, p < 0.00002
      respectively) and also revealed a significantly longer total sleep time with SaO2
      < 90% in this group (183.0 vs 55.0 min, p < 0.0005). We did not find any
      differences between both study groups in the parameters obtained in PSG with
      nCPAP trial therapy. CONCLUSIONS: OSA patients who decide to be treated with
      nCPAP are more obese, have a higher BMI and demonstrate a more severe disease
      assessed by PSG.

PMID- 17175976
TI  - [Obstructive sleep apnea in shift workers].
AB  - The aim of the study was to compare intensity of sleep disordered breathing in
      standard nocturnal polisomnography (PSG) and diurnal PSG after night shift in
      shift workers with obstructive sleep apnea syndrome. METHODS: 25 shift workers
      (24 M, 1 F), aged 45,4 +/- 9,1 yrs, of mean BMI 31,9 +/- 4,02 kg/m2 were studied.
      Nocturnal PSG and diurnal PSG after night shift were performed in all
      participants. RESULTS: The mean apnea/hypopnea index (AHI) in diurnal PSG was
      higher than AHI in nocturnal PSG, 47,8+/- 27,4/h vs 38,0 +/-24,1/h respectively,
      (p<0,05). Not significant tendency towards higher oxygen desaturation index (ODI)
      in diurnal PSG was observed, 40,4 +/-25,5/h vs 31,9 +/-25,8/h respectively.
      CONCLUSION: The study demonstrated that there is a significant increase in AHI in
      diurnal PSG after night shift compared to standard night PSG in shift workers
      with OSAS. This may negatively influence diagnosis and treatment.

PMID- 17175977
TI  - [Obstructive sleep apnoea syndrome in younger and older age groups--differences
      and similarities].
AB  - The prevalence of OSA rises with age, however it is also diagnosed in patients
      below the age of 35 years. Aim of the paper was the camparison of the severity
      and clinical features of OSA in young and elderly subjects. The study was a
      retrospective analysis of 561 subjects aged > 65 yrs and 319 subjects aged < 35
      yrs who were investigated in our Sleep Laboratory between 1992-2005 due to
      snoring or daytime sleepiness. They all underwent full polisomnography or a
      limited recording. In patients with diagnosed OSA (AHI > 10) we initiated CPAP
      therapy. RESULTS: OSA was diagnosed in 383 (63,3%) older patients and in 144
      (45,1%) younger patients. BMI was significantly higher in younger subjects than
      in older (32,2+/-6,9 vs 28,9+/-5,1 kg/m2). The prevalence of OSA among women was
      significantly higher in older patients than in younger (26,4 vs 5,8%). Younger
      patients with OSA had a significantly higher AHI (42,7+/-32,1 vs 32,2+/-18,4) and
      a longer duration of apneas expressed as percentage of total sleep time spent in
      apnea (31,6+/-23,2 vs 26,5+/-17,7%). CPAP therapy was initiated in 185 older
      patients and 41% of them continue therapy. In younger group patients CPAP therapy
      was started in 51 patients and 47% of them continue therapy. The mean therapeutic
      pressure was significantly higher in younger patients with OSA (9,2+/-2,2 vs
      8,2+/-2,2 cmH2O). CONCLUSIONS: 1/ OSA is more frequent in elderly patients ; 2/
      in young patients OSA is more severe and requires higher pressures in CPAP
      therapy; 3/ OSA among women is four time more frequent in older patients than in
      younger.

PMID- 17175978
TI  - [Familial clustering of symptoms typical for OSAS].
AB  - The aim of the study was to compare the incidence of obstructive sleep apnoea
      syndrome (OSAS) symptoms in relatives of subjects with OSAS and in relatives
      without OSAS but with clinical symptoms of this disease. The study group
      consisted of 186 relatives of patients with OSAS and 117 relatives of patients
      with symptoms of OSAS in whom the disease was not confirmed by polysomnography.
      They were all mailed a questionnaire with questions concerning anthropometric
      data, the presence of symptoms typical for OSAS and the presence of concomitant
      diseases. Analysis of the obtained data revealed an increased frequency of
      snoring, sleep apnea and nycturia in the relatives of patients with OSAS when
      compared to relatives of patients without OSAS, but the difference was not
      statistically significant. The incidence of daytime OSAS symptoms was
      significantly higher in the group of relatives of patients with OSAS. No
      differences in the incidence of arterial hypertension, ischaemic heart disease
      and diabetes mellitus were found.

PMID- 17175979
TI  - [The influence of 3 weeks therapy with continuous positive airway pressure on
      serum leptin and homocysteine concentration in patients with obstructive sleep
      apnea syndrome].
AB  - Obstructive sleep apnea (OSA) is one of the most often sleep disturbance. Not
      treated patients have 2-3 times more risk for death because of the cardiovascular
      diseases. Leptin and homocysteine are the risk factors for cardiovascular
      diseases. Treatment by nCPAP has positive influence for health care and reduction
      of hypertension in this group. The aim of this study was to evaluate an effect of
      3 weeks nCPAP therapy on a serum leptin and homocysteine concentrations in
      patients with OSA. MATERIALS AND METHODS: The study group consisted of 48 male
      patients in the age x=51,2?7,5 years old, OSA was diagnosed by polisomnographic
      study The leptin concentration was evaluated by RIA methods (HUMAN LEPTIN RIA
      KIT), the homocysteine concentration was evaluated byAxis Homocysteine EIA test.
      Patients were treated by nCPAP during 3 weeks. Only 29 patients were effectively
      treated for this time. The compliance was: 5.07 +/-1.81 h RESULTS: In the group
      of 29 patients the serum leptin and homocysteine concentration before and after
      treatment were 11,05+/-5,59 ng/mL vs 11,07+/-7,16 ng/mL i 10,98+/-2,79 micromol/L
      vs 10,34+/-2,99 micromol/L. In the all study group the statistical important
      correlation between leptin and AHI, mean and minimal saturation overnight,
      fibrinogene concentration, BMI, WHR, waist circumference, heart rate and between
      homocysteine and heart rate were observed. CONCLUSIONS: 3 weeks therapy does not
      have any effect on leptin and homocysteine concentrations in the studied group of
      patients with OSA. Serum leptin concentration correlates with AHI, TMB90, as well
      as with mean and minimal saturation during a sleep. This indicates a potentially
      higher risk of cardiovascular diseases in the studied group.

PMID- 17175980
TI  - [Bronchial obstruction reversibility test in the assessment of COPD severity-
      controversies].
AB  - The GOLD and ERS/ATS guidelines recommend the post-bronchodilator FEV1 (%
      predicted) to define the severity of chronic obstructive pulmonary disease
      (COPD). Yet in various publications authors analyze the pre-bronchodilator value
      or do not clearly state which value was used when the bronchial reversibility
      test was performed. The guidelines established by the Polish Respiratory Society
      (PRS) do not specify if performing the reversibility test is necessary to
      estimate the COPD severity and suggest a reversibility test evaluation which
      differs from that in the ERS/ ATS and GOLD recommendations. AIM: to assess the
      changes in the degree of severity of COPD in the classification based upon the
      pre- and post-bronchodilator FEV1 and to compare the interpretation of the
      reversibility test as suggested by GOLD and ATS/ ERS and the PRS. METHODS: 145
      COPD patients (67F, 78M, mean age 67.5+/-8.9 yrs) with a negative bronchial
      obstruction reversibility test (salbutamol 400 microg) were enrolled to the
      study. For each patient the degree of COPD severity using the pre- and
      postbronchodilator FEV1 was established. The pre- and post-bronchodilator
      classifications were compared. Differences in the interpretation of the
      reversibility test according to the GOLD and ATS/ ERS and the Polish guidelines
      were analyzed. RESULTS: In 22 subjects (15.2%) the degree of disease severity
      changed after salbutamol. The changes were most frequent in the group of severe
      and very severe COPD (77.3% of changes). In 1 patient (0.7%) post-bronchodilator
      severity was greater than before salbutamol intake. In 7 patients (4.8%) the post
      bronchodilator FEV1/FVC exceeded 70%, thus excluding the diagnosis of COPD. Of
      all the 145 negative (according to the ATS/ ERS and GOLD criteria) reversibility
      tests in 24 cases (16.6%) the test was positive when the criteria recommended by
      PRS were applied. CONCLUSIONS: the bronchial obstruction reversibility test is
      essential in the diagnosis and assessment of severity of COPD. Despite poor
      obstruction reversibility in this disease the use of pre-bronchodilator FEV1 in
      the assessment of COPD severity may be misleading and is an obstacle in the
      comparative analysis of studies in the domain of this disease. Differences in the
      guidelines for the management of COPD may also hinder comparative studies and
      influence epidemiologic data.

PMID- 17175982
TI  - [Efficacy and safety of levofloxacin treatment of community--acquired pneumonia
      in hospitalized patients].
AB  - The aim of this prospective study was to determine the efficacy and safety of
      levofloxacin in the treatment of community-aquired pneumonia (CAP) in outpatient
      with ineffective antibiotic management, requiring hospitalization. The examined
      group included 25 patients (11 M, 14 F) of mean age 70+/-17,5 years with
      abnormalities in X-ray on admission to hospital. Risk factors for pneumonia and
      previous antibacterial therapy were analyzed. In the hospital they were treated
      for 7 days with levofloxacin 500 mg twice a day administred intravenously. Body
      temperature, blood cell count, ESR, CRP, AST, ALT, LDH, CPK, creatine, urea,
      potassium, sodium, ABG, and ECG were measured on admission and in the 3-rd and 7-
      th day of therapy. The chest X-rays were performed and analyzed on hospital
      discharge. 18 patients were aged > 65 yrs, cardiovascular diseases co-existed in
      14, COPD in 9, smoking habit in 12, renal failure in 3, diabetes in 3 and alkohol
      addiction in 1 cases. On admission 4 patients had respiratory failure, 10
      hypoxaemia. During therapy a decrease of body temperature (p<0,001),
      concentration of CRP (p<0,004) and LDH (p<0,03), CPK (p<0,04) and increase of
      PaO2 (p<0,012) were observed. The changes of other parameters were not
      statistically significant. We did not observe any changes in ECG. On discharge
      from the hospital in 16 patients complete regression and in 6 patients partial
      regression of lesions in chest X-ray examination were observed. In 3 patients
      levofloxacin therapy was noneffective: in 2 because of persistent high body
      temperature after 3 days of treatment and in 1 patients because of recurrent of
      fever. Adverse events were mild. Transient exacerbation of renal failure was
      observed in 3 patients. Our study demonstrates that levofloxacine ni dose 2x500
      mg given intravenously for 7 days is effective and safe in treatment of CAP in
      patients with previously ineffective antibacterial therapy.

PMID- 17175981
TI  - [Maximal respiratory pressures and exercise tolerance in patients with COPD].
AB  - Many authors reported respiratory muscle function impairment in patients with
      chronic obstructive pulmonary disease (COPD). Impaired respiratory muscle
      function may contribute exercise intolerance which is frequently observed in this
      disease. AIM OF THE STUDY: was to determine the influence of respiratory muscle
      function on exercise capacity in patients with COPD. METHODS: 23 patients with
      stable COPD aged 62.7 +/- 9.3 years (6F, 17M; mean post-bronchodilator FEV1 =
      47.9 +/-12.4% value predicted) participated in the study. Exercise capacity was
      assessed by the six-minute walk test and the incremental cardiopulmonary exercise
      test (CPET) on a treadmill. Maximal respiratory pressures (PImax, PEmax) were
      evaluated before and directly after CPET. RESULTS: The mean peak oxygen uptake
      (VO max) was 27.2 +/- 6.1 mlO2/min/kg and the mean distance walked during the
      6MWT was 569.4 +/- 101.7 m. Both PIMax and PE max decreased significantly after
      maximal exercise (71.4 +/-23.0 vs 63.6 +/- 22.2 cmH2O, p = 0.001 and 124.9 +/-
      46.5 vs 112.3 +/- 46.6 cm H2O, p = 0.02 respectively). No correlation between
      VO2max and the 6-minute walk distance and the maximal respiratory pressures was
      found. We observed a negative correlation between the 6-minute walk distance and
      the difference between the pre- and post CPET maximal inspiratory pressure.
      CONCLUSIONS: respiratory muscle function is impaired in patients with COPD but
      this does not affect exercise performance. Exercise causes a decrease of the
      respiratory muscle strength.

PMID- 17175983
TI  - [The influence of influenza vaccination on asthma and chronic obstructive
      pulmonary disease].
AB  - Respiratory infections are the most common causes of exacerbations of asthma and
      chronic obstructive pulmonary disease (COPD). The influenza vaccinations are
      recommended in prophylaxis of respiratory infections. The aim of our study was to
      evaluate the influence of influenza vaccinations on asthma or COPD. 178 patients
      (55.1% with asthma, 44.9% with COPD) of Out-patient Clinic of Department of
      Internal Diseases, Pulmonology and Allergology of Warsaw Medical University
      filled the questionnaires. In 2003/2004 season 43.3% (77) of all were vaccinated
      against influenza. The frequency of vaccinations was significantly higher in
      patients >65 years of age 58.4% (45) than in younger ones [41.6% (32)]. The
      number of exacerbations decreased more than twice comparing the time before and
      after immunization: 1.7+/-1.5 and 3.9+/-2.4 per year respectively (p<0.00001).
      CONCLUSIONS: The influenza vaccinations is a useful method of decreasing the
      number of exacerbations in patients with asthma and COPD. The elder patients are
      vacacinated more often than younger ones. The frequency of vaccinations among
      patients with asthma and COPD is still not satisfactory.

PMID- 17175984
TI  - [Pulmonary mycobacteriosis--the diagnostic challenge. The authors' experience].
AB  - The diagnosis of NTM-related pulmonary disease is based on clinical symptoms,
      radiological features and several positive cultures of one and the same NTM
      species from samples obtained from the respiratory tract. Short hospitalization
      usually does not enable sufficient diagnostic procedures to meet the diagnostic
      criteria, and this may lead to the reduction of diagnostic sensitivity. The aim
      of the study was to draw attention to NTM-related pulmonary disease, to share the
      authors' experience in the diagnosing of pulmonary mycobacteriosis and to
      indicate the possibilities of improving the diagnostic accuracy in this disease.
      A group of 31 patients with sputum, bronchial washing and/or bronchoalveolar
      lavage fluid (BALF) NTM-positive cultures was selected from a cohort of 245
      patients evaluated for tuberculous and nontuberculous mycobacterial diseases
      (total number of 1277 specimens were invastigated). In two of them NTM related
      pulmonary disease was diagnosed (caused by M. kansasii and M. avium) at the
      course of initial evaluation. In the remaining 29 patients the microbiological
      data did not allow to establish the diagnosis of mycobacterial lung disease
      mainly due to a small number of samples from the respiratory tract. From this
      group 13 patients were reevaluated within 3 - 6 months from the initial
      investigation. This allowed to identify two new cases of mycobacteriosis (M.
      kansasii and M. avium). Thus among 31 patients with NTM positive cultures from
      respiratory tract specimens 4 patients (4/31, 12,9%) met the diagnostic criteria
      for mycobacterial disaease. CONCLUSION: Microbiological analysis of an adequate
      number of samples in symptomatic patients with radiological features suggestive
      for NTM-related pulmonary disease increses the diagnostic sensitivity in
      pulmonary mycobacteriosis. Identification of the species in positive cultures is
      of great importance.

PMID- 17175985
TI  - [The mycolic acids analysis with HPLC technique in drug susceptibility testing of
      Mycobacterium tuberculosis strains].
AB  - The aim of this study was to evaluate the utility of the quantitative analysis of
      mycolic acids by HPLC technique in drug susceptibility testing of the M.
      tuberculosis isolates to the first-line antituberculous drugs: isoniazid and
      rifampicin. Drug susceptibility of the 30 clinical M.tbc isolates was examined by
      the mycolic acids analysis with HPLC technique and results were compared to the
      proportion method on solid L-J medium and liquid medium in MGIT system. In HPLC
      method drug susceptibility of M. tuberculosis strains was described by TAMA index
      defined as the ratio of the total area under mycolic acids peaks (TAMA) from
      cultures with drug to the TAMA of control. At critical concentrations of drugs,
      TAMA indexes of resistant strains were >0.5, and TAMA indexes of susceptible
      strains were <0.05. The average error of the TAMA analysis was +/- 9.5% The
      quantitative analysis of mycolic acids by HPLC gives results compatible with
      standard proportion method and is a reliable method for determination of drug
      susceptibility of M. tuberculosis.

PMID- 17175986
TI  - [Identification of Mycobacteriaceae species based on the hsp-65 gene polymorphism
      analysis by PCR - RFLP].
AB  - The polymorphism of the short fragment of the heat shock protein 65 encoding gene
      was evaluated by the PCR - RFLP technique described by Telenti and further
      developed by Devallois for identification of mycobacterial species in routine
      laboratory work. We analysed 58 strains representing 25 different mycobacterial
      species (24 reference strains and 34 clinical isolates). The results obtained by
      PCR-RFLP and HPLC identification techniques were highly concordant The results
      were compatible for 87,5% (21 / 24) reference strains and for 97,1% (33/34)
      clinical isolates. The PCR - RFLP method allowed for accurate identification
      mycobacterial species, especially pathogenic strains. Restriction patterns
      obtained for 25 species of Mycobacteriaceae genus could help in constructing the
      data base and algorithms used in routine laboratory practice.

PMID- 17175987
TI  - [Macrophage phenotype in induced sputum in asthma subjects].
AB  - Macrophages represent the most predominant immune effector cells in the alveolar
      spaces and conducting airways and are known to express activated phenotype. The
      study was aimed at assessing the differences in cellular profile and the
      expression of selected surface markers on sputum macrophages in asthma and
      healthy subjects. 17 healthy subjects (never smoked) and 10 mild asthma subjects
      treated with glucocorticosteroids were enrolled into the study. For macrophage
      phenotyping a immunocytochemistry method was used with commercially available
      antibodies anti: CD14, CD71, CD11b and CD54. The nonparametric Mann Whitney U
      test was applied for data comparison, p value <0.05 being regarded as
      significant. The total number of cells were increased in asthma patients 4.81+/
      5.27x 10(6) /ml vs healthy 2.8+/-2.15 x 10(6)/ml and it was statistically
      significant. Statistically significant increase in the percentage of eosinophils
      was observed in mild asthma subjects. No differences were found between the
      proportion in macrophages and lymphocytes. The macrophage phenothype in induced
      sputum differed in both groups. The expression of CD11b was higher in asthma
      group and the difference was statistically significant. The proportion of
      macrophages with the expression of CD 14, CD 71 and CD54 was comparable in both
      groups. Macrophage phenotyping during glucocorticosteroid therapy is useful in
      the assessment of inflammatory process in asthma subject.

PMID- 17175988
TI  - [Effect of phosphodiestrase 4 inhibitor (rolipram) on experimental allergic
      asthma-guinea pig model].
AB  - Selective phosphodiesterases (PDE) inhibitors are the new group of antiasthmatic
      drugs, which integrate antiinflammatory activity with bronchoconstriction
      counteraction. Selective inhibitors of phosphodiesterase type 4 are used as
      alternative or assist drugs in treatment of respiratory system diseases. So far
      glucocorticosteroids remain the most efficient and widely used medicine in the
      treatment of asthma. However application of glucocorticosteroid is greatly
      limited because of numerous side effects, what induce to permanent search for new
      antiasthmatic drugs. Examination new substances are executed on animal models.
      Guinea pig model is widely used to research course of asthmatic reaction. This
      model is especially convenient on the ground of that: lung is major shock organ,
      airway respond to histamine, animals demonstrated early asthmatic reaction (EAR)
      and late asthmatic reaction (LAR), eosinophils flow in bronchoalveolar space
      during LAR. In ovalbumin (OA) sensitized guinea pigs hypersensitivity reaction
      breaks out as a result of OA provocation. Aims of our experiments, execute on
      guinea pig model were to determine the influence of rolipram (PDE 4 inhibitor) on
      modulation experimental asthmatic reaction and comparison activity of rolipram
      versus dexamethasone in attribution to chosen parameters of allergic reaction
      such as: lung resistance, influx of protein and inflammatory cells in airways,
      and mastocytes degranulation. Experiments were made on guinea pigs sensitized and
      provoked with ovalbumin The obtain data indicate that rolipram was effective in
      reduction the rise of lung resistance during EAR, restricted influx of
      eosinophils to bronchoalveolar space between 1,5 and 24 hours after provocation,
      and reduced increase of histamine concentration in bronchoalveolar lavage fluid
      (BALf). Rolipram had no influence on number of neutrophils present in BALf.
      Dexamethasone in double dose of 1,2mg/kg effectively bordered the growth of lung
      resistance during EAR, and broke influx of eosinophils and neutrophils to
      bronchoalveolar space.

PMID- 17175989
TI  - [The interpretation of carbon monoxide diffusing capacity test depending of
      hemoglobin concentration].
AB  - The carbon monoxide diffusion capacity (DLCO) is among others dependent of the
      hemoglobin value. The result of DLCO test in patients with anemia change when we
      adjust DLCO for hemoglobin (Hb) concentration. The aim of the study was to
      estimate if the differences between result of DLCO and DLCO/VA before and after
      adjust the Hb value can change the interpretation of the test in the group with
      normal and low value of Hb. The study group consist of 25 patients with normal
      level of Hb (group A) and 21 ones with anemia (group B). All studied have been
      done spirometry, bodypletyzmografy and DLCO test. All tests were made on the
      SensorMedics. The DLCO test was made in the single breath diffusing capacity
      program Results. The values of the Hb in the group A were above 13 g/dl for
      female and 14 g/dl for man. In the group B the Hb value were less then 10 g/dl.
      In the group A the middle Hb concentration was 14,49 +/- 1,36g/dl. DLCO and
      DLCO/VA before and after Hb value adjusted were 91,4 +/-17,98 vs 90,7 +/- 17,58 %
      i 101,5 +/- 19,46 vs 100,7 +/- 18,65% (p>0,05). In the group B the middle Hb
      concentration was 8,77 +/- 0,97 g/dl. DLCO and DLCO/VA before and after Hb value
      adjusted were: 57,05+/-17,55 vs 72,19+/-25,27% i 67,57+/-11,18 vs 84,66+/-14,62%
      (p< 0,05). CONCLUSIONS: 1. The were non statistically important change in the
      DLCO test results after consideration on Hb level in the studied group without
      anemia, so in the patients with normal level of Hb the DLCO test result doesn't
      change the interpretation of the test after the consideration on Hb concentration
      2. In patients with anemia we shout adjust the Hb value to the DLCO test because
      the results with out this can completely change the interpretation of the test
      and clinical diagnosis

PMID- 17175990
TI  - [Serum concentration of homocysteine and the risk of atherosclerosis in patients
      with obstructive sleep apnea syndrome].
AB  - AIM: to evaluate usefulness of serum homocysteine concentration in assessing the
      risk of atherosclerosis in patients with OSAS. MATERIALS AND METHODS: 47 patients
      (mean age 50.6+/-10.3 years, mean BMI 31.52+/-6.04 kg/m2), with OSAS confirmed by
      polisomnography and 12 healthy snoring subjects (mean age 42.8 +/-16.8 years,
      mean BMI 26.9+/-2.95 kg/m2) were enrolled to the study. OSAS patients were
      divided into two groups - subjects with normal blood pressure (group A, n=32,
      mean age 51.3+/-10.3 years, mean BMI 30.6+/-4.4 kg/m2) and subjects with arterial
      hypertension (group B, n=15, mean age 52.7+/-9.8 years, mean BMI 31.4+/-5.0
      kg/m2). None of the study subjects was treated with statins or fibrates. Serum
      concentration ofhomocysteine, uric acid, glucose level and lipid profile was
      evaluated in all subjects. RESULTS: We found significant abnormalities in the
      lipid profile in all the study groups. The mean concentrations of cholesterol
      (mg/dL), triglycerides (mg/dL) and homocysteine (micromol/L) were as follows:
      215.0+/-34.2, 200.0+/-173.0, 8.2+/-2.9 in group A, 216.5+/-43.1, 189.3+/-138.8,
      8.40+/-1.67 in group B. 195.0+/-32.9, 154.3+/-133.0, 9.3+/-2.1 in the control
      group. No significant correlation between the homocysteine concentration and
      level of cholesterol or triglycerides was found. CONCLUSIONS: the serum
      concentration of homocysteine seems not to be a good marker in the evaluation of
      the risk of atherosclerosis in patients with OSAS.

PMID- 17175991
TI  - [Mediastinal lymphangioma].
AB  - 47-year-old women was admitted to the clinic for diagnosis of an incidentally X
      ray detected enlargement of the medistinum shadow. In the past, the patient had
      been operated for lymphangioma of the right forearm. Chest computer tomography
      (CT) showed an abnormal mass in the front mediastinum with spherical structures,
      which density could indicate high-protein contents. In the right mammarian gland
      an oval cyst (23-15 mm), similar in character to the lesion in the mediastinum
      was found. The lymphangiomatic character of the lesion with the extension up to
      the superior aperture of the thorax was confirmed with magnetic resonans imaging
      (MRI). Due to the extensive changes and lack of symptoms, the patient was
      disqualified for surgical treatment and remains under further observation.

PMID- 17175992
TI  - [Diagnosis of tuberculous lymphadenitis based on the fine needle aspiration
      samples analysis].
AB  - Tuberculous lymphadenitis is one of the most common extrapulmonary manifestations
      of tuberculosis. The most common lymph nodes involved are in the cervical region.
      Lymphadenitis due to M. tuberculosis generally presents with enlarging neck lymph
      nodes over weeks or months associated with fever, weight loss and fatigue. Fine
      needle aspiration (FNA) of affected lymph nodes has been shown to yield a high
      sensitivity and specificity in the diagnosis of tuberculous lymphadenitis.
      Specimens should be examined cytologically, as well as by AFB smear and cultures.
      The time between the onset of symptoms, clinical presentation and final diagnosis
      is often too long. We present a case of 60 years old man with tuberculous
      lymphadenitis, initially suspected of lymphoproliferative disease.

PMID- 17175993
TI  - [Breast carcinoma and anaplastic gastric carcinoma with pleural metastases in
      patient after mastectomy 30 years ago].
AB  - We describe a case of two simultaneous malignancies--anaplastic gastric carcinoma
      with pleural metastases and left breast carcinoma. These malignancies were
      recognized in 78-year old woman after right mastectomy performed 30 years ago.
      Additionaly, during diagnostic procedures rectal polypus found during colonoscopy
      occurred to be adenoma tubulovillosum. Her parents died from malignancies--mother
      from gastric cancer and father from pulmonary carcinoma. One should remember that
      there is always possibility of simultaneous development of more than one primary
      malignancies in one patient and neoplastic disease is an important cancer risk
      factor. This observation confirms the important role of genetic factors in the
      pathogenesis of malignant diseases.

PMID- 17175994
TI  - [Chronic obstructive pulmonary disease needs adjectives: "guiltless" COPD,
      "asthma like" and "emphysemal" COPD].
AB  - The author proposes an extension of terminology of COPD by introducing to certain
      situations the adjectives "guiltless" (for patient who never smoked) , "asthma
      like" (for patients with symptoms with reversible bronchoconstriction and
      eosinophilia) and emphysemal COPD. The aim of this proposal is better
      understanding of certain events in the disease and subsequently proper treatment.

PMID- 17175995
TI  - [Malaria control in the Colombian Pacific Coast].

PMID- 17175996
TI  - [Ticks of the Republic of Colombia. 1940].

PMID- 17175997
TI  - [First case report of Mammomonogamus (Syngamus) laryngeus human infection in
      Colombia].
AB  - First case report of Mammomonogamus (Syngamus) laryngeus human infection in
      Colombia Parasitic nematodes of the genus Mammomonogamus affect the respiratory
      tract of domestic mammals. The male and female of M. laryngeus remain in
      permanent copula so that the pair appears as a "Y'. To date, a few more than 100
      cases of human infections by this parasite have been reported in the biomedical
      literature. This report describes the first infected patient in Colombia. He had
      a persistent and productive cough and after an episode of coughing a pair of
      worms were expelled in sputum with total clinical recovery. Since there is scant
      clinical information about this parasite, this report includes a description of
      the adult worms, a summary of the epidemiology and the clinical manifestations in
      humans. Photographs are presented to facilitate future identification by
      morphological characteristics.

PMID- 17175998
TI  - [Evaluation of an educational strategy on malaria in rural areas of the Colombian
      Pacific Coast].
AB  - INTRODUCTION: Health education interventions have proved effective in improving
      knowledge, preventing practices and decreasing occurrence of malaria. OBJECTIVE:
      To evaluate the impact of the educational intervention "The World of Malaria:
      Let's Learn to Manage it in Community" developed in Colombian malarial areas, in
      terms of increasing knowledge, preventive practices, treatment-seeking, and
      decreasing malaria occurrence. MATERIALS AND METHODS: A quasi-experimental post
      test study with a non-equivalent control group was carried out. Four hundred and
      fifty people living in 20 rural villages were interviewed. These localities were
      randomly selected from 110 intervened localities. Paired "t" test was performed
      to evaluate the effect on malaria knowledge of the community health workers
      (n=243). The effect of the intervention on the effect variables was measured by
      using logistic regression and by comparing people who were exposed and non
      exposed to the educational strategy. RESULTS: Knowledge on malaria in community
      health workers increased after the intervention (p < 0.05). In the communities,
      170/447 (38%) interviewed individuals had contact with the intervention in the
      communities. Those exposed to the intervention showed improvements in knowledge
      about breeding sites (OR: 2.53, 95% IC:1.7-3.76), bed-nets use (OR:1.81, 95%
      IC:1.10-2.97) and a decrease in self-medication with antimalarial drugs (OR:1.97,
      95% IC: 1.04-3.73). Contact with the intervention reduced reported episodes of
      malaria (OR:0.58, 95% CI: 0.39-0.87). CONCLUSION: Significant improvements in
      preventive practices may be achieved with educational interventions, which in
      turn may reduce malaria ocurrence.

PMID- 17175999
TI  - [Plasmodium vivax malaria: treatment of primary attacks with primaquine, in three
      different doses, and a fixed dose of chloroquine, Antioquia, Colombia, 2003
      2004].
AB  - INTRODUCTION: Chloroquine (CQ) and primaquine (PQ) are used in Colombia for
      treatment of uncomplicated vivax malaria but there are few efficacy studies of
      this scheme. OBJECTIVES: (a) to investigate the clinical picture of vivax malaria
      in adult patients; (b) to evaluate the antimalarial treatment response to the
      standard scheme CQ-PQ; (c) to compare the efficacy of the standard scheme and two
      alternative schemes with equal dose of CQ and different PQ dose; (d) to identify
      the adverse effects of CQ-PQ treatment. MATERIALS AND METHODS: Randomized,
      nonblind design; three groups, defined according to total dose of PQ: 45, 105 and
      210 mg. All patients received CQ (1500 mg, in 48 hours), which was followed by
      PQ. Patients were recruited in Turbo and El Bagre. The follow-up period was 28
      days. Antimalarial treatment response was classified according to the WHO-2001
      protocol (early failure, late failure, adequate response). RESULTS: In total 228
      patients were recruited, 18 were lost between days 4 and 27; the antimalarial
      treatment response was evaluated in 210. The clinical findings were similar to
      those described by other authors. Parasitaemia clearance was confirmed during the
      first 24 hours of CQ treatment in 11% of patients. At 48 hours 66% and at 72
      hours 97% of patients were negative. All patients (210) displayed adequate
      treatment response to the CQ-PQ treatment. The different doses of PQ did not
      affect this response. CONCLUSIONS: CQ-PQ should be conserved as the first
      treatment choice and should be evaluated in other areas. Simultaneous
      administration of CQ and PQ is proposed.

PMID- 17176000
TI  - [Effects of an educational and participatory community intervention on malaria
      control in Buenaventura, Colombia].
AB  - INTRODUCTION: A four-component, non randomized, primary-care based intervention
      for malaria control was implemented in Buenaventura, Colombia. OBJECTIVE: To
      evaluate the effect of the applied intervention on knowledge about malaria,
      attention of febrile events and frequency of malaria occurrence in three
      communities of Buenaventura. MATERIALS AND METHODS: A post-intervention
      evaluation with a non-equivalent control group was performed. Two non-intervened
      groups (those residing more and less than six months, respectively, in the area)
      and one intervened group were identified. We interviewed 661 women household
      heads. Contact was defined as having been exposed to at least one of the four
      intervention components. RESULTS: Fourteen percent of the respondents had contact
      with the intervention. The attention of a febrile episode was better in those who
      had contact with the intervention than in the nonintervened ones who had resided
      in the area for more than six months. Those without contact and with less than
      six months stay in the area reported lower use of bed-nets (OR:0.46; 95% CI:0.23
      0.93) and less fumigation practices (OR:0.38; 95% CI:0.19-0.75). The analysis of
      the malaria case trend showed a reduction in the proportion of cases contributed
      by the intervened communities, from 25% to 17%, six years after the intervention.
      CONCLUSION: An educational strategy is effective to enhance knowledge and modify
      the practices of the urban population of Buenaventura with respect to malaria.

PMID- 17176001
TI  - [Cost-effectiveness analysis of two strategies for malaria control in the urban
      area of Buenaventura, Colombia].
AB  - INTRODUCTION: Costs and results of two alternatives for malaria control were
      compared. One constituted by the activities of the National Programme, the other
      by the integration of an educational strategy denominated "Integrated
      Alternative" (IA) into the national program in Buenaventura on the Pacific Coast
      of Colombia. Objective. To evaluate the cost-effectiveness of two alternatives
      for malaria control in the urban area of Buenaventura. MATERIALS AND METHODS. A
      cost-effectiveness analysis was carried out from an institutional and household
      perspective. Institutional costs were obtained by reviewing records of
      institutions that implemented each alternative; household costs were obtained
      from interviews. Effectiveness measurement was the number of averted cases per
      10,000 inhabitants. RESULTS: Institutional costs of National Programme and
      Integrated Alternative were U.S. dollars 3766 and U.S. dollars 24,932.8
      respectively. Average household cost in the zone where National Programme was
      implemented was U.S. dollars 36.2, while in the zone where IA was applied it was
      U.S. dollars 28.4. The number of averted cases per 10,000 inhabitants was 12.9
      (CI 95% -6.0; 31.8) for National Programme and 264.6 (CI 95% 254.1; 275.1) for
      Integrated Alternative. The institutional cost-effectiveness ratios of National
      Programme and Integrated Alternative were U.S. dollars 292.4 and U.S. dollars
      92.2, respectively. CONCLUSION: Integration of the educational strategy into the
      National Programme was the most cost-effective alternative. Our data suggest that
      the educational strategy should be added to the National Programme activities.

PMID- 17176002
TI  - [Outbreaks of human rabies transmitted by vampire bats in Alto Baudo and Bajo
      Baudo municipalities, department of choco, Colombia, 2004-2005].
AB  - INTRODUCTION: During months May to July 2004, a rabies outbreak in the Embera
      community of Birrinchao, in the Purricha river basin department of Choc6 was
      reported with 14 human deaths. Another rabies outbreak was reported in January
      2005 in the black communities of Pato and Nauca in the neighboring municipality
      of Alto Baudo with 3 human deaths. OBJECTIVES: To describe the largest outbreaks
      of human rabies transmitted by vampire bats reported in Colombia to date. To
      describe the diagnostic laboratory techniques used, and the activities undertaken
      for the control of rabies in the area. To discuss the epidemiologic significance
      and public health implications of these rabies outbreaks. MATERIALS AND METHODS:
      Rabies diagnosis was achieved by direct immunofluorescence, inoculation of mice
      and immunohistochemistry. Typing of the virus was achieved by indirect
      immunofluorescence using monoclonal antibodies. Rabies control activities were
      undertaken in Bajo Baudo consisting in a population census, human vaccination and
      application of antirabies sera, vaccination of dogs and cats, and application of
      anticoagulant to bats. RESULTS: Four human cases were confirmed as positive for
      rabies in both rabies outbreaks. Another 13 rabies cases in humans were inferred
      by strong epidemiological links. Rabies antigenic variant 3 was identified in the
      samples studied. Rabies control activities were conducted for a human rabies
      outbreak caused by vampire bats. CONCLUSIONS: The human rabies outbreak in Bajo
      Baudo has been the largest reported in Colombia. It was caused by vampire bats,
      showing that these animals are a threat for human health. The implementation of
      control strategies for this kind of epizootic outbreaks is needed in South
      America. It remains unknown whether there is a link between this outbreak and one
      reported 6 months later in the neighboring municipality of Alto Baudo.

PMID- 17176003
TI  - [Characterization by pulsed-field gel electrophoresis of Salmonella typhimurium
      isolates recovered in the acute diarrheal disease surveillance program in
      Colombia, 1997-2004].
AB  - INTRODUCTION: In Colombia Salmonella Typhimurium is the second most frequently
      isolated Salmonella serotype (after S. Enteritidis) from human clinical samples.
      This serotype represents 28.2% (n=468) of the 1659 Salmonella isolates recovered
      by the Instituto Nacional de Salud (INS) Acute Diarrheal Diseases Surveillance
      Program from 1997 to 2004. Previously, little was known about the molecular
      attributes of these strains and commonality of genetic subtypes among S.
      Typhimurium isolated from humans in Colombia. OBJECTIVE: The purpose of this
      study was to characterize S. Typhimurium isolates circulating in Colombia using
      pulsed-field gel electrophoresis in order to establish genetic profiles and
      determine their potential relatedness. MATERIALS AND METHODS: 468 S. Typhimurium
      isolates were submitted to INS by 14 Public Health Laboratories from January 1997
      to December 2004. The pulsed-field gel electrophoresis was performed using
      restriction enzyme Xbal according to the PulseNet standard protocol (CDC,
      Atlanta). Restriction pattern analysis and cluster definition were performed
      using Molecular Analyst Fingerprinting II software. RESULTS: 180 distinct
      electrophoretic patterns were obtained. Pattern COINJPX.X01.0062 was the most
      common (21.3% of the 473 isolates, n=101), followed by COINJPX.X01.0001 (8.4%,
      n=40), COINJPX.X01.0058 (3%, n=13), COINJPX.X01.0003 (2.5%, n=12),
      COINJPX.X01.0066 (2.3%, n=11), and COINJPX.X01.0108 (1.4%, n=6).
      COINJPX.X01.0001, was the most prevalent pattern among S. Typhimurium isolated in
      Bogota from 1997-2002, but appeared to be replaced both in Bogota and nationally
      by COINJPX.X01.0062 in 2003-2004. Cluster analysis demonstrated three distinct
      groups with 53% and 82% similarity indicating heterogeneity within the serotype.
      CONCLUSIONS: The study provides important electrophoretic pattern baseline data,
      which will be useful for prospective real-time comparison of profiles of future
      isolates. Cluster detection using this method will facilitate outbreak detection
      and will enhance our ability to find common sources for seemingly unrelated
      infections.

PMID- 17176005
TI  - [Validity of the brief Zung's scale for screening major depressive episode among
      the general population from Bucaramanga, Colombia].
AB  - INTRODUCTION: Brief scales for identiFying depressive disorder are as useful as
      long scales for screening. However, a validated scale with these characteristics
      is not avalaible in Colombia. OBJECTIVE: To design a brief Zung's self-rating
      depression scale in order to screen major depressive episodes among adults
      dwelling in the general community. MATERIALS AND METHODS: After filling-out the
      20-item Zung's self-rating depression scale, the ten items with the higher
      correlation with total score were selected. Construct and criterion validity were
      computed for these ten items. RESULTS: The ten chosen items showed an internal
      consistency of 0.803, one factor that accounted for 36.6% of the variance;
      sensitivity was 95.5%; specificity, 70.3%; Cohen's kappa, 0.415; and area under
      receptor-operator curve, 0.898. CONCLUSIONS: The brief Zung's self-rating
      depression scale exhibits psychometric properties similar to the long version.
      This brief scale can be used as a screening device in the general population.

PMID- 17176004
TI  - [Molecular characterization of an outbreak caused by CTX-M-12-producing
      Klebsiella pneumoniae in a Colombian hospital's neonatal intensive care unit].
AB  - INTRODUCTION: Molecular characterisation of Klebsiella pneumoniae strains is a
      tool that assits in the reduction of the disemination of drug resistance and the
      control of nosocomial infections that are caused by this pathogen. Objective.
      Molecular description of an outbreak of nosocomial infection caused by Klebsiella
      pneumoniae in a neonatal intensive care unit in a tertiary level hospital in
      Bogota. METHODS: Eleven Klebsiella pneumoniae isolates were analysed. Production
      of Extended Spectrum Beta-Lactamases was verified by agar diffusion tests.
      Isoelectric points of the enzymes were determined by isoelectric focusing. The
      bla(CTX-M-12) gene was detected by PCR and pulsed field gel electrophoresis
      genotyping was done. RESULTS: All the isolates were Extended Spectrum Beta
      Lactamase producers. Pulsed field gel electrophoresis and BOX-PCR genotyping
      grouped two isolates from hospital objects and eight infection-causing isolates
      into a single epidemic clone. The isolate from a thermometer was not grouped into
      the epidemic clone and showed a different resistance pattern. Isoelectric
      focusing revealed simultaneous beta-lactamase production having different
      isoelectric points. PCR amplification revealed the presence of the bla(CTX-M-12)
      gene in the 11 isolates studied. CONCLUSION: This is the first report of a
      molecularly characterised outbreak of CTX-M-12-producing Klebsiella pneumoniae
      from Colombia. The results of this study provide additional evidence of the
      global dissemination of CTX-M ESBL and the need for epidemiological follow-up in
      our hospitals.

PMID- 17176006
TI  - [Antimicrobial resistance in gram negative bacteria isolated from intensive care
      units of Colombian hospitals, WHONET 2003, 2004 and 2005].
AB  - INTRODUCTION: Surveillance systems play a key role in the detection and control
      of bacterial resistance. It is necessary to constantly collect information from
      all institutions because the mechanisms of bacterial resistance can operate in
      different ways between countries, cities and even in hospitals in the same area.
      Therefore local information is important in order to learn about bacterial
      behaviour and design appropriate interventions for each institution. Between
      January 2003 and December 2004, the Centro Internacional de Entrenamiento e
      Investigaciones Medicas (CIDEIM) developed a surveillance project in 10 tertiary
      hospitals in 6 cities of Colombia. OBJECTIVES: Describe the trends of antibiotic
      resistance among the isolates of Escherichia coli, Klebsiella pneumoniae,
      Pseudomona aeruginosa, Acinetobacter baumannii and Enterobacter cloacae, five of
      the most prevalent nosocomial Gram negative pathogens. MATERIALS AND METHODS: The
      susceptibility tests were performed by automated methods in 9 hospitals and by
      Kirby Bauer in 1 hospital. Antibiotics with known activity against Gram
      negatives, according to the Clinical Laboratory Standards Institute guidelines,
      were selected. The laboratories performed internal and external quality controls.
      During the study period, the information was downloaded monthly from the
      databases of each microbiology laboratory and sent to CIDEIM where it was
      centralized in a database using the system WHONET 5.3. RESULTS: The high
      resistance rates reported especially for A. baumannii, evidenced the presence of
      multidrug resistant bacteria in both ICUs and wards at every studied institution.
      CONCLUSIONS: The creation of a national surveillance network to improve our
      capabilities to detect, follow up, and control the antibiotic resistance in
      Colombia is urgently needed.

PMID- 17176008
TI  - [Molecular typing of Listeria monocytogenes isolated from clinical and food
      samples].
AB  - INTRODUCTION: Listeria monocytogenes is an emergent foodborne pathogen acquired
      by the ingestion of contaminated food. This bacterium causes a disease called
      listeriosis, whose mortality rate world wide is around 20% to 30%, reaching up to
      80% in cases of neonatal infections. The random amplified polymorphic DNA
      technique allows different isolates to be distinguished and characterized at the
      molecular level, which can provide useful information about the diversity of this
      pathogen in Colombia. OBJECTIVE: To molecularly characterize different L.
      monocytogenes isolates from food and clinical samples using this technique to
      determine possible relationships among these two origins. MATERIALS AND METHODS:
      Thirty eight L. monocytogenes isolates were analyzed; 22 from human clinical
      samples and 16 from food processing plants and food using two 10bp primers
      (HLW74, Arbitrary). The data were analyzed using Quantity One and SYN-TAX
      software. RESULTS: A high percentage of polymorphism was detected with both
      primers (HLWL-74, 81.81%; Arbitrary, 85.71%). Two major lineages were found,
      which were divided into four major clusters (A, B C and D) and great genetic
      diversity was observed. Most of the clinical isolates were grouped within the
      same cluster, and were more distantly related to the food isolates. CONCLUSION:
      The results of this study demonstrate a high degree of genetic diversity of DNA
      polymorphisms among the L. monocytogenes isolates circulating in Colombia, which
      could reflect phenotypic and pathogenic differences in these isolates.

PMID- 17176007
TI  - [Colombian haplotypes of the Gaucher disease-causing N370S mutation may originate
      from a possible common ancestral haplotype].
AB  - INTRODUCTION: Gaucher disease is a pan-ethnic condition characterised by
      glucosylceramide accumulation in macrophages due to glucocerebrosidase
      deficiency. Its gene, GBA, has been mapped to 1q21 and mutation N370S is the main
      cause of the disease in western populations, including Colombia. OBJECTIVE: To
      asses the degree of association between N370S mutation and the alleles of five
      microsatellites near the mutation site in the GBA locus in nine Colombian Gaucher
      patients, from the Cundinamarca-Boyaca region. MATERIALS AND METHODS: DNA from
      patients bearing the N370S mutation, their closest relatives, and 30 controls was
      taken to PCR-amplify the markers: D1S305, D1S2624, DIS2777, ITG6.6.2 and 5GC3.2.
      Allele frequencies were calculated, haplotypes inferred and linkage
      disequilibrium levels between marker alleles and N370S were also estimated.
      RESULTS: Eleven N370S chromosomes were obtained. A consensus N370S haplotype
      consisting of the alleles: 222-314-260-301-172 (base pairs) was identified. Each
      allele corresponding to markers 5GC3.2, ITG6.6.2, D1S277, D1S2624 and D1S305,
      respectively. There was statistically significant linkage disequilibrium between
      the alleles of 222, 314, 260, 301 base pairs and the N370S mutation. CONCLUSION:
      A conserved fraction of the haplotypes suggests that N370S may be present among
      patients and stem from a single ancestral chromosome for which the ethnic origin
      is still unclear.

PMID- 17176009
TI  - [Soluble factors with inhibitory activity against type 1 Human Immunodeficiency
      Virus].
AB  - Soluble factors with inhibitory activity against type 1 Human Immunodeficiency
      Virus The pathogenesis of HIV-1 infection is a complex process that depends on
      multiple factors, including viral and host immune and genetic characteristics.
      This leads to a variable pattern of disease progression among those HIV-1-exposed
      individuals who become infected, while there are a number of individuals who
      remain healthy and HIV-1 seronegative despite being serially exposed to HIV-1.
      These variable outcomes of HIV-1 exposure suggest that there are mechanisms of
      natural resistance to HIV-1 infection. Although several genetic and adaptive
      immune mechanisms of resistance have been reported in some exposed seronegative
      and long-term non-progressor individuals, the mechanisms involved in controlling
      the establishment and progression of HIV-1 infection are not fully understood.
      Several soluble factors, such as defensins, chemokines, interferons and
      ribonucleases, among others, produced by cells of the immune system and
      epithelial tissues, have a broad anti-viral activity that might play a role as
      protective mechanisms during HIV-1 exposure. A better understanding of the
      mechanisms and role of these soluble factors during the natural resistance to HIV
      1 infection may have important implications for the design of novel therapeutic
      strategies to combat the morbidity and mortality associated with the HIV-1
      pandemic.

PMID- 17176010
TI  - Postoperative factors affecting neurological recovery after surgery for cervical
      spondylotic myelopathy.
AB  - OBJECT: Many prognostic factors associated with surgery for cervical spondylotic
      myelopathy (CSM) have been detailed in the literature. All of these factors,
      however, are defined preoperatively. If it is possible to clarify factors
      influencing surgical results that can be modulated after surgery, then the
      overall results of surgery may improve. The purpose of this study was to
      elucidate such postoperative factors affecting neurological recovery. METHODS:
      The authors assessed the surgical outcomes obtained in 183 patients with CSM who
      underwent expansive open-door laminoplasty between 1993 and 2004 and who
      underwent follow up for a minimum of 1 year. They classified the cases into two
      groups according to the degree of neurological recovery: an excellent recovery
      group, comprising patients in whom the recovery rates were greater than 75%, and
      a poor recovery group, composed of patients in whom the recovery rates were lower
      than 30%. Comparisons of various clinical and imaging parameters revealed that
      the mean age at surgery was significantly lower in patients in the excellent
      recovery group than that in the poor recovery group. Therefore, the authors
      repeated the same analyses after adjustment for age. Postoperative cervical range
      of motion (ROM) was significantly more reduced in the excellent recovery group
      than in the poor recovery group. There was a significant positive correlation
      between reduced cervical ROM and recovery rate in the poor recovery group.
      CONCLUSIONS: Dynamic stress may ameliorate functional recovery of the degenerated
      spinal cord even after sufficient decompression. Postoperative preservation of
      cervical ROM may not always be beneficial for neurological recovery in patients
      with CSM.

PMID- 17176011
TI  - Cervical pedicle screw fixation in 100 cases of unstable cervical injuries:
      pedicle axis views obtained using fluoroscopy.
AB  - OBJECT: The authors conducted a study to introduce the imaging technique in which
      pedicle axis views are obtained using fluoroscopy to match the screw entry point
      with pedicle orientation and to report the clinical results and safety of
      cervical pedicle screw fixation (PSF) in patients treated for unstable cervical
      injuries. METHODS: One hundred consecutive patients with unstable cervical
      injuries underwent PSF in which the authors used fluoroscopic imaging to acquire
      pedicle axis views. There were 87 men and 13 women whose mean age was 42.5 years.
      The accuracy of PS placement was examined postoperatively using axial computed
      tomography (CT) and oblique radiography. Screw malpositioning was classified
      either as screw exposure (< 50% of the screw outside the pedicle) or pedicle
      perforation (> 50% of the screw outside the pedicle boundaries). The mean
      operative time was 97.6 minutes, and the mean estimated blood loss was 221 ml.
      Local vertebral alignment around the injured segment measured 6.0 degrees of
      kyphosis preoperatively and 6.7 degrees of lordosis postoperatively. Solid
      posterior bone fusion was achieved in all but three patients who died shortly
      after surgery. There was no secondary dislodgment of instrumentation in 95% of
      these 97 cases. Of the 419 cervical PSs, 43 (10.3%) were of the screw-exposure
      type and 17 (4.0%) of the pedicle-perforation type. There were two surgery
      related complications: one penetration of a probe into the vertebral artery and
      one radiculopathy. There were six postoperative complications: two cases of
      instrumentation failure associated with loss of correction, three cases of
      correction loss (> 10 degrees), and one case of deep wound infection.
      CONCLUSIONS: Solid posterior fusion without secondary dislodgment of hardware was
      demonstrated in 95% of the cases. The incidence of complications associated with
      cervical PSF was not high. Postoperative CT scanning showed that 17 (4.0%) of 419
      screws perforated the pedicle. It appears that fluoroscopy performed using
      pedicle axis views improves the accuracy and safety of cervical PS insertion.

PMID- 17176012
TI  - Microscopic bilateral decompression through unilateral laminotomy for lumbar
      canal stenosis in patients undergoing hemodialysis.
AB  - OBJECT: Microscopic bilateral decompression through a unilateral laminotomy
      (MBDUL) is a minimally invasive technique used to treat lumbar canal stenosis
      (LCS). In the present study, MBDUL was performed to treat LCS in eight patients
      undergoing hemodialysis. METHODS: Surgical outcomes were evaluated using the
      Japanese Orthopaedic Association (JOA) scale (highest possible score 29). The JOA
      scale was administered preoperatively, at 1 month and 3 months postoperatively,
      and at the final follow-up examination. One patient refused to undergo the
      postoperative assessment after the 1-month examination; the mean follow-up
      duration of the remaining seven patients was 24 months (range 18-31 months). The
      mean age at the time of surgery was 62 years (range 48-76 years), and the mean
      duration of hemodialysis therapy was 21.4 years (range 3-28 years). All patients
      could walk within 2 days of surgery. The mean angle of the straight leg-raising
      (SLR) test was 53.8 degrees preoperatively, and this increased to 69.4 degrees
      postoperatively. Six patients felt enhancement of sciatica or leg pain when
      performing the SLR test preoperatively, a finding that was absent postoperatively
      at least until the final follow-up examination. The mean preoperative JOA score
      was 11.6 (range 4-22), and the score markedly improved to 19.8 (range 15-23) at 1
      month and 20.6 (range 16-25) at 3 months. The mean JOA score decreased to 17.1
      (range 12-25) at the final follow-up examination, but this decrease was
      attributed to other physical disorders. CONCLUSIONS: The authors conclude that
      MBDUL is a safe and effective surgical treatment for patients undergoing
      hemodialysis who are suffering from LCS.

PMID- 17176013
TI  - Quality of life of lumbar stenosis-treated patients in whom the X STOP
      interspinous device was implanted.
AB  - OBJECT: This study was conducted to compare the quality of life (QOL) in patients
      with neurogenic intermittent claudication (NIC) secondary to lumbar spinal
      stenosis (LSS). Using the 36-Item Short Form (SF-36) questionnaire, the authors
      compared the results obtained in patients treated with the X STOP Interspinous
      Process Decompression (IPD) System with those obtained in patients who underwent
      nonoperative therapies. METHODS: Patients with LSS were enrolled in a prospective
      2-year multicenter study and randomized either to the X STOP or nonoperative
      group. The SF-36 survey was used to assess the QOL before treatment and at 6
      weeks, 6 months, 1 year, and 2 years posttreatment. An analysis of variance was
      used to compare individual pre- and posttreatment mean SF-36 domain scores
      between the two groups and within each treatment group. At all posttreatment time
      points, the authors observed the following: (1) mean domain scores in X STOP
      treated patients were significantly greater than those in patients treated
      nonoperatively, with the exception of the mean General Health (GH), Role
      Emotional, and Mental Component Summary scores at 2 years; and (2) mean
      posttreatment domain scores documented in X STOP-treated patients were
      significantly greater than mean pretreatment scores, with the exception of mean
      GH scores at 6, 12, and 24 months. CONCLUSIONS: The results of this study
      demonstrate that the X STOP device is significantly more effective than
      nonoperative therapy in improving the QOL in patients with LSS. The results are
      comparable with those reported in other studies involving traditional
      decompressive techniques for LSS and suggest that the X STOP implant can provide
      an effective treatment compared with nonoperative and conventional surgical
      therapies.

PMID- 17176014
TI  - An evaluation of vascular anatomy for minilaparotomic anterior L4-5 procedures.
AB  - OBJECT: The complexity of the vascular anatomy pertinent to the L4-5
      intervertebral disc space has led to difficulties when performing the anterior
      approach to the lumbar spine. The purpose of the present study was to evaluate
      the variations of the great vessels to match the imaging-documented axial anatomy
      with the surgical exposure. METHODS: The authors analyzed data obtained in 223
      patients who had undergone mini-open anterior lumbar surgery involving the L4-5
      disc. The preoperative magnetic resonance images or computed tomography scans
      were evaluated by examiners blinded to the surgical approach to determine the
      vascular configuration. All complications of the procedures were described. Two
      major variations of the vascular configuration were delineated according to the
      location of the bifurcation of the inferior vena cava. On images showing the
      lower margin of the L-4 vertebra, the anatomy in 182 patients (81%) was
      classified as Type A because the inferior vena cava (IVC) was not bifurcated; in
      38 patients (17%) it was classified as Type B because the IVC was bifurcated.
      Type A could be subdivided into Types A1 and A2 according to whether the aorta
      was bifurcated (A2) or not (A1) on the same image. The surgical exposure used was
      above the bifurcations (in Type A) and below the bifurcations (in Type B). The
      major complications were three venous injuries, and the leading complication was
      sympathetic dysfunction in 14 patients, which in most cases resolved
      spontaneously. CONCLUSIONS: Careful preoperative evaluation of the vascular
      anatomy is essential to conducting successful anterior lumbar surgery. The
      determination of an appropriate approach can contribute to a reduction of
      unnecessary vascular retraction and a consequent decrease in vascular
      complications.

PMID- 17176015
TI  - Thoracic myelopathy caused by ossification of the ligamentum flavum: clinical
      features and surgical results in the Japanese population.
AB  - OBJECT: Data obtained in patients with thoracic myelopathy caused by ossification
      of the ligamentum flavum (OLF) were retrospectively reviewed to clarify clinical
      features and surgical outcomes in the Japanese population. METHODS: Seventy-two
      patients who underwent surgery for OLF-induced myelopathy in the Miyagi
      Prefecture, Japan, between 1988 and 2002 were observed for at least 2 years.
      Clinical data were collected from medical and operative records. The patients
      were evaluated pre- and postoperatively using the modified Japanese Orthopaedic
      Association (JOA) scale (maximum score 11). The relationships among various
      factors (age, sex, and preoperative duration of symptoms) affecting the
      preoperative severity of myelopathy and postoperative improvement were also
      examined. CONCLUSIONS: In this series the surgical outcome was relatively good
      and depended on the severity of myelopathy; thus early and correct diagnosis is
      required to avoid poorer results. The male/female ratio was 3:2 and the mean
      patient age at surgery was 61 years for men and 68 for women. The patients
      commonly noticed numbness or pain in their lower legs or gait disturbances. In a
      total of 104 decompressed intervertebral disc levels, more than 80% of the
      ossified ligaments were at the T9-10 level or lower. The mean preoperative JOA
      score of 5.1 improved to 7.9 after an average of 46 months. The postoperative
      results statistically depended on the preoperative severity of myelopathy. Among
      studies of patients with OLF-related myelopathy, the present study had the
      largest sample size, which should help clarify the clinical features of OLF
      myelopathy.

PMID- 17176016
TI  - Accuracy and safety of pedicle screw fixation in thoracic spine trauma.
AB  - OBJECT: The authors evaluated the accuracy of placement and safety of pedicle
      screws in the treatment of unstable thoracic spine fractures. METHODS: Patients
      with unstable fractures between T-1 and T-10, which had been treated with pedicle
      screw (PS) placement by one of five spine surgeons at a referral center were
      included in a prospective cohort study. Postoperative computed tomography scans
      were obtained using 3-mm axial cuts with sagittal reconstructions. Three
      independent reviewers (C.B., V.S., and D.G.) assessed PS position using a
      validated grading scale. Comparison of failure rates among cases grouped by
      selected baseline variables were performed using Pearson chi-square tests.
      Independent peri- and postoperative surveillance for local and general
      complications was performed to assess safety. Twenty-three patients with unstable
      thoracic fractures treated with 201 thoracic PSs were analyzed. Only PSs located
      between T-1 and T-12 were studied, with the majority of screws placed between T-5
      and T-10. Of the 201 thoracic PSs, 133 (66.2%) were fully contained within the
      pedicle wall. The remaining 68 screws (33.8%) violated the pedicle wall. Of
      these, 36 (52.9%) were lateral, 27 (39.7%) were medial, and five (7.4%) were
      anterior perforations. No superior, inferior, anteromedial, or anterolateral
      perforations were found. When local anatomy and the clinical safety of screws
      were considered, 98.5% (198 of 201) of the screws were probably in an acceptable
      position. No baseline variables influenced the incidence of perforations. There
      were no adverse neurological, vascular, or visceral injuries detected
      intraoperatively or postoperatively. CONCLUSIONS: In the vast majority of cases,
      PSs can be placed in an acceptable and safe position by fellowship-trained spine
      surgeons when treating unstable thoracic spine fractures. However, an
      unacceptable screw position can occur.

PMID- 17176017
TI  - Translaminar screw fixation in the upper thoracic spine.
AB  - OBJECT: The use of pedicle screws (PSs) for instrument-assisted fusion in the
      cervical and thoracic spine has increased in recent years, allowing smaller
      constructs with improved biomechanical stability and repositioning possibilities.
      In the smaller pedicles of the upper thoracic spine, the placement of PSs can be
      challenging and may increase the risk of damage to neural structures. As an
      alternative to PSs, translaminar screws can provide spinal stability, and they
      may be used when pedicular anatomy precludes successful placement of PSs. The
      authors describe the technique of translaminar screw placement in the T-1 and T-2
      vertebrae. METHODS: Seven patients underwent cervicothoracic fusion to treat
      trauma, neoplasm, or degenerative disease. Nineteen translaminar screws were
      placed, 13 at T-1 and six at T-2. A single asymptomatic T-2 screw violated the
      ventral laminar cortex and was removed. The mean clinical and radiographic follow
      up exceeded 14 months, at which time there were no cases of screw pullout, screw
      fracture, or progressive kyphotic deformity. CONCLUSIONS: Rigid fixation with
      translaminar screws offers an attractive alternative to PS fixation, allowing the
      creation of sound spinal constructs and minimizing potential neurological
      morbidity. Their use requires intact posterior elements, and care should be taken
      to avoid violation of the ventral laminar wall.

PMID- 17176018
TI  - Comparison of polyetheretherketone cages with femoral cortical bone allograft as
      a single-piece interbody spacer in transforaminal lumbar interbody fusion.
AB  - OBJECT: Transforaminal lumbar interbody fusion (TLIF) is an accepted alternative
      to circumferential fusion of the lumbar spine in the treatment of degenerative
      disc disease, spondylolisthesis, and recurrent disc herniation. To maintain disc
      height while arthrodesis takes place, the technique requires the use of an
      interbody spacer. Although titanium cages are used in this capacity, the two most
      common spacers are polyetheretherketone (PEEK) cages and femoral cortical
      allografts (FCAs). The authors compared the clinical and radiographic outcomes of
      patients who underwent TLIF with pedicle screw fixation, in whom either a PEEK
      cage or an FCA was placed as an interbody spacer. METHODS: The charts and x-ray
      films obtained in 39 patients (age range 33-68 years, mean 44.7 years) who
      underwent single-level TLIF between October 2001 and April 2004 and in whom
      either a PEEK cage (18 patients) or FCA (21 patients) was placed as an interbody
      spacer were evaluated in a retrospective study. Radiological outcome was based on
      fusion rate and a comparison of the initial postoperative lordotic angle on
      standing lateral radiographs with that at long-term follow up (mean follow up
      15.1 months, minimum 12 months). To control for variations in radiographic
      magnification, the authors used lordotic angle as an indirect measure of disc
      space height. Clinical outcome was assessed using the Oswestry Disability Index
      (ODI). There were no major complications in either group. Radiographically
      documented fusion occurred in all patients in the PEEK group and 95.2% of those
      in the FCA group. Pseudarthrosis developed in one patient in the FCA group, and
      this patient underwent additional surgery. In both groups, the mean lordotic
      angle changed by less than 2.20 degrees during the postoperative period, and the
      mean postoperative ODI score was more than 40 points lower than the mean
      preoperative score. There was no significant difference between the two groups in
      mean change in lordotic angle (p = 0.415) and mean change in ODI score (p =
      0.491). CONCLUSIONS: Both PEEK cages and FCAs are highly effective in promoting
      interbody fusion, maintaining postoperative disc space height, and achieving
      desirable clinical outcomes in patients who undergo TLIF with pedicle screw
      fixation. The advantages of PEEK cages include a lower incidence of subsidence
      and their radiolucency, which permits easier visualization of bone growth.

PMID- 17176019
TI  - Approach to the cervical portion of the vagus nerve via the posterior cervical
      triangle: a cadaveric feasibility study with potential use in vagus nerve
      stimulation procedures.
AB  - OBJECT: The authors describe a technique in which the cervical portion of the
      vagus nerve is exposed during procedures such as neuroma resection or, more
      commonly, during the placement of a vagus nerve stimulator. METHODS: To test
      their hypothesis that a posterolateral approach to the vagus nerve may be
      feasible and efficacious, the authors performed dissection of the left-sided
      vagus nerve in 13 adult cadavers. The carotid sheath was exposed via the
      posterior cervical triangle, and the vagus nerve was identified posterolaterally.
      Measurements were made of the length of available nerve, and the anatomical
      approach was documented. As part of a comparison study regarding the available
      length of nerve, the authors exposed the left vagus nerve in five additional
      adult cadavers via a standard anterior approach to the carotid sheath, and
      compared the results obtained with each technique. A mean length of 12 cm of the
      vagus nerve was isolated when using the posterior approach to the carotid sheath,
      whereas a mean length of 11 cm of the nerve was documented when using the
      anterior approach. With the aforementioned posterior approach, no obvious injury
      occurred to the vagus nerve or other local neurovascular structures such as the
      spinal accessory nerve. CONCLUSIONS: Evaluation of the findings obtained in the
      present cadaveric study showed that a posterior approach to the vagus nerve is
      feasible. The technique for posterior exposure of the carotid sheath may prove
      useful in surgical exposures of the vagus nerve when a standard anterior method
      is not possible.

PMID- 17176020
TI  - Pseudoglandular schwannoma of the cauda equina. Case report.
AB  - The authors present a case of pseudoglandular schwannoma with immunohistochemical
      findings consistent with epithelial metaplasia. Pseudoglandular schwannoma is a
      rare morphological variant of benign schwannoma characterized by the presence of
      glandlike structures lined with Schwann cells. To the best of the authors'
      knowledge, this is only the fifth case of pseudoglandular schwannoma reported in
      the literature. Clinical, imaging, and pathological findings are described. The
      pathological findings were consistent with a pseudoglandular schwannoma composed
      of typical Schwann cells arranged in an Antoni B pattern, with numerous large
      pseudocystic spaces. Serial immunohistochemical studies of tissue sections
      revealed that the cells lining the pseudoglandular spaces were not only diffusely
      reactive for S100 protein, but also demonstrated focal positivity for epithelial
      membrane antigen and cytokeratins AE and AE3. The particular immunohistochemical
      features of incompletely differentiated Schwann cells in the present case give
      support to the metaplastic theory of the origin of glandlike structures in benign
      peripheral nerve sheath tumors.

PMID- 17176021
TI  - An unusual transverse sacral fracture treated with early decompression. Case
      report.
AB  - The authors describe the case of a patient who sustained a transverse sacral
      fracture (TSF) associated with a depressed laminar fracture in a personal
      watercraft accident. The patient underwent early surgery, which allowed a quick
      recovery. To the best of the authors' knowledge, the mechanism of injury and type
      of fracture have not been previously described or classified in cases of TSF.

PMID- 17176022
TI  - Trombone tongue: a new clinical sign for significant medullary compression at the
      craniovertebral junction. Case report.
AB  - The authors describe a previously unreported clinical sign that may indicate the
      onset of significant compression of the medulla oblongata in cases of
      craniovertebral junction abnormalities. This 17-year-old boy presented with mild
      bilateral leg weakness. Imaging studies revealed severe basilar invagination and
      a marked Chiari malformation. While awaiting surgery, his tongue developed an
      involuntary constant protrusion-intrusion repetitive motion. The onset of this so
      named "trombone tongue" sign was followed shortly afterward by rapidly
      progressive spastic tetraparesis. After the authors performed a transmaxillary
      clivectomy, foramen magnum decompression, and occipitocervical fusion, they noted
      that the abnormal tongue motion promptly resolved and the tetraparesis gradually
      improved. The authors discuss their current understanding of the central control
      of tongue movements and present a hypothesis on the pathogenesis of trombone
      tongue based on the neuroanatomical basis of another abnormal tongue movement
      sign, lingual myoclonus.

PMID- 17176023
TI  - Vertebral artery injury in C-1 lateral mass screw fixation. Case illustration.

PMID- 17176024
TI  - Dissecting aneurysm of the thoracic posterior spinal artery. Case illustration.

PMID- 17176025
TI  - Charite lumbar artificial disc retrieval: use of a lateral minimally invasive
      technique. Technical note.
AB  - Indications for total disc replacement (TDR) may include implant loosening,
      malposition, displacement, early wear, and infection. Each indication is likely
      to require different preoperative planning, testing, and strategies. Preoperative
      planning is the first and most important step in performing a TDR revision. An
      organized approach reduces operative time, minimizes risks, decreases stress, and
      increases the success rate. Primary revision of a failed total disc arthroplasty
      can be planned as a posterior fusion, leaving the TDR device in place, but an
      unstable anterior column may require retrieval and revision of the interbody
      device. An anterior revision approach is associated with significant risk due to
      scarring and adhesions resulting from the primary procedure, making mobilization
      of the vessels very difficult, especially at the L4-5 bifurcation. The authors
      describe a new alternative for retrieval and revision of a TDR device. They
      present the details of two cases of TDR device revision in which they performed a
      minimally invasive extreme-lateral interbody fusion to effect a safer access
      route that avoids vascular structures and the creation of scar tissue.

PMID- 17176026
TI  - Some novel polymeric nanocomposites.
AB  - The nanocomposites described here all involve polymers and were chosen because
      they are already of commercial importance, show some promise of becoming so, or
      simply seem interesting. The field is so broad that some topics are mentioned
      only very briefly, and there is considerable emphasis on the polysiloxane
      nanocomposites studied by the author's research group. Some are typically
      prepared using techniques very similar to those used in the new sol-gel approach
      to ceramics, with either the polymer or the ceramic being the continuous phase.
      Other dispersed phases include particles responsive to an applied magnetic field,
      intercalated or exfoliated platelets obtained from clays, mica, or graphite,
      silsesquioxane nanocages, nanotubes, dual fillers, porous particles, spherical
      and ellipsoidal polymeric particles, and nanocatalysts. Also described are some
      typical studies involving theory or simulations on such particle reinforcement.
      Experiments on ceramics modified by dispersed polymers are equally interesting,
      but there is less relevant theory. Many of the fields mentioned have become so
      vast that the approach taken here is simply to describe general approaches and
      characteristics of the composites, list some specific examples, and provide
      leading references (with some emphasis on studies that are relatively recent or
      in the nature of reviews).

PMID- 17176027
TI  - Fascination with the conformational analysis of succinic acid, as evaluated by
      NMR spectroscopy, and why.
AB  - A serendipitous effort to use NMR spectroscopy to determine the conformational
      preferences of succinate monoanion opened a Pandora's box of unexpected
      uncertainties as to what influences such preferences of succinic acid in its
      various ionization states, not only in water but also in other less polar protic
      solvents, as well as a range of aprotic solvents. The dianion in aprotic solvents
      shows substantial gauche preferences, which give the appearance of violating
      Coulomb's law.

PMID- 17176028
TI  - Ionic-liquid-supported synthesis: a novel liquid-phase strategy for organic
      synthesis.
AB  - Soluble ionic liquids have recently been used as supports for catalyst/reagent
      immobilization and synthesis in homogeneous solution phase. The wide range of
      ionic liquid supports available makes their use as supports compatible with most
      common chemistries. The solubility properties of these ionic liquid supports can
      be tuned by the variation of cations and anions to make them phase separate from
      less polar organic solvents and aqueous media. The ionic-liquid-supported species
      can therefore be purified from the reaction mixture by simple washings. Ionic
      liquid-supported catalysts and reagents have been prepared and used, and they are
      easily recovered and reused. Parallel and combinatorial libraries of small
      molecules have been synthesized. Ionic-liquid-supported synthesis (ILSS) has been
      applied to the preparation of oligopeptides and oligosaccharides. The comparison
      of ILSS with solid-phase synthesis, soluble-polymer-supported synthesis, and
      fluorous phase synthesis has been highlighted where applicable.

PMID- 17176029
TI  - "Four-dimensional" protein structures: examples from metalloproteins.
AB  - The fact that an object, for example, a protein, possesses a three-dimensional
      structure seems an obvious concept. However, when the object is flexible, the
      concept is less obvious. Growing experimental data over several decades show that
      proteins are not rigid objects, but they may sample more or less wide ranges of
      different conformations. To stress this concept, we propose to call the range of
      sampled conformations the "fourth dimension" of the protein structure. Nuclear
      magnetic resonance is a precious technique to define this fourth dimension.
      Examples of conformational heterogeneity taken from the realm of metalloproteins
      and their functional implications are discussed.

PMID- 17176030
TI  - Reversible binding of heme to proteins in cellular signal transduction.
AB  - Heme plays critical roles in numerous biological phenomena. Recent evidence has
      uncovered a new role of heme in cellular signal transduction, and its mechanism
      involves reversible binding of heme to proteins. This Account highlights the
      novel function of heme as an intracellular messenger in the regulation of gene
      expression and ion channel function.

PMID- 17176031
TI  - Peptide dendrimers as artificial enzymes, receptors, and drug-delivery agents.
AB  - The dendritic architecture applied to peptides provides a practical entry into
      globular macromolecules resembling proteins. A modular design was chosen using a
      divergent synthesis on solid support alternating proteinogenic alpha-amino acids
      with branching diamino acids, producing peptide dendrimers with a molecular
      weight of 3-5 kDa. Initial studies focused on models for hydrolases and produced
      esterase peptide dendrimers featuring histidine as the key catalytic residue.
      Variations of amino acid composition and the branching diamino acid led to
      enantioselective catalysts. Rate accelerations of k(cat)/k(uncat) = 90,000 were
      obtained when the design was changed to monomeric peptide dendrimers alternating
      two amino acids with the branching unit. A combinatorial approach was developed
      allowing for the preparation of large libraries (>60,000 members), which were
      screened for B12 binding and catalytic activity. The peptide dendrimers were also
      investigated for drug delivery. Glycopeptide dendrimers conjugated to colchicine
      selectively inhibited the proliferation of targeted cells, whereas colchicine
      alone displayed high toxicity.

PMID- 17176032
TI  - Synthesis and biological properties of sequence-specific DNA-alkylating pyrrole
      imidazole polyamides.
AB  - In recent years, many diseases including cancer and hereditary and viral diseases
      have been understood at the DNA sequence level. Direct control of the expression
      level of a specific gene would provide a promising approach for knowledge-based
      therapy. N-Methylpyrrole (Py) and N-methylimidazole (Im) polyamides are a new
      type of small compound that precisely bind to the minor groove of the DNA duplex
      in a sequence-specific fashion and recruit alkylating agents to the target
      sequence. We designed and synthesized a series of sequence-specific alkylating Py
      Im polyamide conjugates that selectively alkylate predetermined DNA sequences. We
      have demonstrated that sequence-specific alkylating agents possess gene-silencing
      activities and a promising potency against human cancer cell lines as well as
      against xenografts of human cancer cell lines. In this Account, we focus on
      recent progress in alkylating Py-Im polyamides with regard to sequence
      specificity and biological activities and the future direction of rational
      molecular design of genetic switches in the postgenome era is described.

PMID- 17176033
TI  - Ground- and excited-state tautomerism in porphycenes.
AB  - Owing to short distances between the inner nitrogen atoms and, therefore, strong
      intramolecular hydrogen bonds, porphycenes display completely different
      tautomeric properties than porphyrins, their constitutional isomers. Tunneling
      splitting caused by delocalization of two inner hydrogen atoms is observed for
      porphycenes isolated in supersonic jets. The barrier to tautomerization is higher
      in the lowest excited singlet state than in the ground state. Still, rapid
      exchange of inner hydrogen atoms is detected in S1. The mechanism of
      tautomerization involves synchronous double hydrogen tunneling, activated by
      excitation of a low-frequency mode, which modulates the NH...N separation. This
      separation can also be strongly altered by peripheral substitution. In
      porphycenes with alkyl substituents on the ethylene bridges, the NH...N distances
      become extremely small. For these derivatives, both trans and cis tautomeric
      forms are detected. Tautomerism in porphycenes was also monitored on a single
      molecule level.

PMID- 17176034
TI  - Polymer chain dynamics in solution probed with a fluorescence blob model.
AB  - This Account describes a new fluorescence tool that characterizes the chain
      dynamics of polymers in solution. This new tool, coined the fluorescence blob
      model (FBM), is employed to analyze the fluorescence decays of polymers randomly
      labeled with pyrene. The FBM yields the number of monomers making up a blob
      (Nblob) where a blob is the volume probed by an excited pyrene. By establishing a
      relationship between Nblob and the lifetime of pyrene used as an internal clock,
      the FBM provides previously unavailable information about polymer chain dynamics
      and opens new venues of research, which are described in this Account.

PMID- 17176035
TI  - Engineering light-gated ion channels.
AB  - Ion channels are gated by a variety of stimuli, including ligands, voltage,
      membrane tension, temperature, and even light. Natural gates can be altered and
      augmented using synthetic chemistry and molecular biology to develop channels
      with completely new functional properties. Light-sensitive channels are
      particularly attractive because optical manipulation offers a high degree of
      spatial and temporal control. Over the last few decades, several channels have
      been successfully rendered responsive to light, including the nicotinic
      acetylcholine receptor, gramicidin A, a voltage-gated potassium channel, an
      ionotropic glutamate receptor, alpha-hemolysin, and a mechanosensitive channel.
      Very recently, naturally occurring light-gated cation channels have been
      discovered. This review covers the molecular principles that guide the
      engineering of light-gated ion channels for applications in biology and medicine.

PMID- 17176037
TI  - Solution state characterization of amyloid beta-derived diffusible ligands.
AB  - A growing body of evidence suggests that soluble oligomeric forms of the amyloid
      beta peptide known as amyloid-derived diffusible ligands (ADDLs) are the toxic
      species responsible for neurodegeneration associated with Alzheimer's disease.
      Accurate biophysical characterization of ADDL preparations is hampered by the
      peptide's strong tendency to self-associate and the effect of factors such as
      ionic strength, temperature, and pH on its behavior. In addition, amyloid
      peptides are known to interact with common laboratory excipients, specifically
      detergents, further complicating the results from standard analytical methods
      such as denaturing polyacrylamide gel electrophoresis. We have studied the
      solution behavior of various amyloid peptide preparations using analytical
      ultracentrifugation and size exclusion chromatography coupled with multiangle
      laser light scattering. Our results indicate that ADDL preparations exist in
      solution primarily as a binary mixture of a monomeric peptide and high-molecular
      mass oligomers. We relate our findings to previously described characterizations
      utilizing atomic force microscopy and electrophoretic methods and demonstrate
      that low-molecular mass oligomers identified by gel electrophoresis likely
      represent artifacts induced by the peptide's interaction with detergent, while
      atomic force microscopy results are likely skewed by differential binding of
      monomeric and oligomeric peptide species. Finally, we confirm that only the high
      molecular mass oligomeric components of an ADDL preparation are capable of
      binding to subpopulations of primary hippocampal neurons in vitro.

PMID- 17176036
TI  - Regulation of DNA repair fidelity by molecular checkpoints: "gates" in DNA
      polymerase beta's substrate selection.
AB  - With an increasing number of structural, kinetic, and modeling studies of diverse
      DNA polymerases in various contexts, a complex dynamical view of how atomic
      motions might define molecular "gates" or checkpoints that contribute to
      polymerase specificity and efficiency is emerging. Such atomic-level information
      can offer insights into rate-limiting conformational and chemical steps to help
      piece together mechanistic views of polymerases in action. With recent advances,
      modeling and dynamics simulations, subject to the well-appreciated limitations,
      can access transition states and transient intermediates along a reaction
      pathway, both conformational and chemical, and such information can help bridge
      the gap between experimentally determined equilibrium structures and mechanistic
      enzymology data. Focusing on DNA polymerase beta (pol beta), we present an
      emerging view of the geometric, energetic, and dynamic selection criteria
      governing insertion rate and fidelity mechanisms of DNA polymerases, as gleaned
      from various computational studies and based on the large body of existing
      kinetic and structural data. The landscape of nucleotide insertion for pol beta
      includes conformational changes, prechemistry, and chemistry "avenues", each with
      a unique deterministic or stochastic pathway that includes checkpoints for
      selective control of nucleotide insertion efficiency. For both correct and
      incorrect incoming nucleotides, pol beta's conformational rearrangements before
      chemistry include a cascade of slow and subtle side chain rearrangements,
      followed by active site adjustments to overcome higher chemical barriers, which
      include critical ion-polymerase geometries; this latter notion of a prechemistry
      avenue fits well with recent structural and NMR data. The chemical step involves
      an associative mechanism with several possibilities for the initial proton
      transfer and for the interaction among the active site residues and bridging
      water molecules. The conformational and chemical events and associated barriers
      define checkpoints that control enzymatic efficiency and fidelity. Understanding
      the nature of such active site rearrangements can facilitate interpretation of
      existing data and stimulate new experiments that aim to probe enzyme features
      that contribute to fidelity discrimination across various polymerases via such
      geometric, dynamic, and energetic selection criteria.

PMID- 17176038
TI  - Ankyrin repeat: a unique motif mediating protein-protein interactions.
AB  - Ankyrin repeat, one of the most widely existing protein motifs in nature,
      consists of 30-34 amino acid residues and exclusively functions to mediate
      protein-protein interactions, some of which are directly involved in the
      development of human cancer and other diseases. Each ankyrin repeat exhibits a
      helix-turn-helix conformation, and strings of such tandem repeats are packed in a
      nearly linear array to form helix-turn-helix bundles with relatively flexible
      loops. The global structure of an ankyrin repeat protein is mainly stabilized by
      intra- and inter-repeat hydrophobic and hydrogen bonding interactions. The
      repetitive and elongated nature of ankyrin repeat proteins provides the molecular
      bases of the unique characteristics of ankyrin repeat proteins in protein
      stability, folding and unfolding, and binding specificity. Recent studies have
      demonstrated that ankyrin repeat proteins do not recognize specific sequences,
      and interacting residues are discontinuously dispersed into the whole molecules
      of both the ankyrin repeat protein and its partner. In addition, the availability
      of thousands of ankyrin repeat sequences has made it feasible to use rational
      design to modify the specificity and stability of physiologically important
      ankyrin repeat proteins and even to generate ankyrin repeat proteins with novel
      functions through combinatorial chemistry approaches.

PMID- 17176039
TI  - Microsomal triglyceride transfer protein is required for yolk lipid utilization
      and absorption of dietary lipids in zebrafish larvae.
AB  - Although the absorption, transport, and catabolism of dietary lipids have been
      studied extensively in great detail in mammals and other vertebrates, a tractable
      genetic system for identifying novel genes involved in these physiologic
      processes is not available. To establish such a model, we monitored neutral lipid
      by staining fixed zebrafish larvae with oil red o (ORO). The head structures,
      heart, vasculature, and swim bladder stained with ORO until the yolk was consumed
      6 days after fertilization (6 dpf). Thereafter, the heart and vasculature no
      longer had stainable neutral lipids. Following a high-fat meal, ORO stained the
      intestine and vasculature of 6 dpf larvae, and whole-larval triacylglycerol (TAG)
      and apolipoprotein B levels increased. Levels of microsomal triglyceride transfer
      protein (Mtp), the protein responsible for packaging TAG and betalipoproteins
      into lipoprotein particles, were unchanged by feeding. Since the developing
      zebrafish embryo expresses mtp in the yolk cell layer, liver, and intestine, we
      determined the effect of targeted knockdown of Mtp expression using an antisense
      morpholino oligonucleotide approach (Mtp MO) on the transport of yolk and dietary
      lipids. Mtp MO injection led to loss of Mtp expression and of lipid staining in
      the vasculature, heart, and head structures. Mtp MO-injected larvae were smaller
      than age-matched, uninjected larvae, consumed very little yolk, and did not
      absorb dietary neutral lipids; however, they absorbed a short chain fatty acid
      that does not require Mtp for transport. Importantly, the vasculature appeared
      unaffected in Mtp MO-injected larvae. These studies indicate that zebrafish
      larvae are suitable for genetic studies of lipid transport and metabolism.

PMID- 17176040
TI  - Structure of ATP-bound human ATP:cobalamin adenosyltransferase.
AB  - Mutations in the gene encoding human ATP:cobalamin adenosyltransferase (hATR) can
      result in the metabolic disorder known as methylmalonic aciduria (MMA). This
      enzyme catalyzes the final step in the conversion of cyanocobalamin (vitamin B12)
      to the essential human cofactor adenosylcobalamin. Here we present the 2.5 A
      crystal structure of ATP bound to hATR refined to an Rfree value of 25.2%. The
      enzyme forms a tightly associated trimer, where the monomer comprises a five
      helix bundle and the active sites lie on the subunit interfaces. Only two of the
      three active sites within the trimer contain the bound ATP substrate, thereby
      providing examples of apo- and substrate-bound-active sites within the same
      crystal structure. Comparison of the empty and occupied sites indicates that
      twenty residues at the enzyme's N-terminus become ordered upon binding of ATP to
      form a novel ATP-binding site and an extended cleft that likely binds cobalamin.
      The structure explains the role of 20 invariant residues; six are involved in ATP
      binding, including Arg190, which hydrogen bonds to ATP atoms on both sides of the
      scissile bond. Ten of the hydrogen bonds are required for structural stability,
      and four are in positions to interact with cobalamin. The structure also reveals
      how the point mutations that cause MMA are deficient in these functions.

PMID- 17176041
TI  - Structure and reaction geometry of geranylgeranyl diphosphate synthase from
      Sinapis alba.
AB  - The crystal structure of the geranylgeranyl diphosphate synthase from Sinapis
      alba (mustard) has been solved in two crystal forms at 1.8 and 2.0 A resolutions.
      In one of these forms, the dimeric enzyme binds one molecule of the final product
      geranylgeranyl diphosphate in one subunit. The chainfold of the enzyme
      corresponds to that of other members of the farnesyl diphosphate synthase family.
      Whereas the binding modes of the two substrates dimethylallyl diphosphate and
      isopentenyl diphosphate at the allyl and isopentenyl sites, respectively, have
      been established with other members of the family, the complex structure
      presented reveals for the first time the binding mode of a reaction product at
      the isopentenyl site. The binding geometry of substrates and product in
      conjunction with the protein environment and the established chemistry of the
      reaction provide a clear picture of the reaction steps and atom displacements.
      Moreover, a comparison with a ligated homologous structure outlined an
      appreciable induced fit: helix alpha8 and its environment undergo a large
      conformational change when either the substrate dimethylallyl diphosphate or an
      analogue is bound to the allyl site; only a minor conformational change occurs
      when the other substrate isopentenyl diphosphate or the product is bound to the
      isopentenyl site.

PMID- 17176042
TI  - Core structure of S2 from the human coronavirus NL63 spike glycoprotein.
AB  - Human coronavirus NL63 (HCoV-NL63) has recently been identified as a causative
      agent of acute respiratory tract illnesses in infants and young children. The
      HCoV-NL63 spike (S) protein mediates virion attachment to cells and subsequent
      fusion of the viral and cellular membranes. This viral entry process is a primary
      target for vaccine and drug development. HCoV-NL63 S is expressed as a single
      chain glycoprotein and consists of an N-terminal receptor-binding domain (S1) and
      a C-terminal transmembrane fusion domain (S2). The latter contains two highly
      conserved heptad-repeat (HR) sequences that are each extended by 14 amino acids
      relative to those of the SARS coronavirus or the prototypic murine coronavirus,
      mouse hepatitis virus. Limited proteolysis studies of the HCoV-NL63 S2 fusion
      core identify an alpha-helical domain composed of a trimer of the HR segments N57
      and C42. The crystal structure of this complex reveals three C42 helices entwined
      in an oblique and antiparallel manner around a central triple-stranded coiled
      coil formed by three N57 helices. The overall geometry comprises distinctive high
      affinity conformations of interacting cross-sectional layers of the six helices.
      As a result, this structure is unusually stable, with an apparent melting
      temperature of 78 degrees C in the presence of the denaturant guanidine
      hydrochloride at 5 M concentration. The extended HR regions may therefore be
      required to prime the group 1 S glycoproteins for their fusion-activating
      conformational changes during viral entry. Our results provide an initial basis
      for understanding an intriguing interplay between the presence or absence of
      proteolytic maturation among the coronavirus groups and the membrane fusion
      activity of their S glycoproteins. This study also suggests a potential strategy
      for the development of improved HCoV-NL63 fusion inhibitors.

PMID- 17176043
TI  - Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase
      LpxC and implications for substrate binding.
AB  - LpxC is a zinc metalloenzyme that catalyzes the first committed step in the
      biosynthesis of lipid A, a vital component of the outer membrane of Gram-negative
      bacteria. Accordingly, the inhibition of LpxC is an attractive strategy for the
      treatment of Gram-negative bacterial infections. Here, we report the 2.7 A
      resolution X-ray crystal structure of LpxC from Aquifex aeolicus complexed with
      uridine 5'-diphosphate (UDP), and the 3.1 A resolution structure of LpxC
      complexed with pyrophosphate. The X-ray crystal structure of the LpxC-UDP complex
      provides the first view of interactions likely to be exploited by the substrate
      UDP group in the "basic patch" of the active site. The diphosphate group of UDP
      makes hydrogen bond interactions with strictly conserved residue K239 as well as
      solvent molecules. The ribose moiety of UDP interacts with partially conserved
      residue E197. The UDP uracil group hydrogen bonds with both the backbone NH group
      and the backbone carbonyl group of E160, and with the backbone NH group of K162
      through an intervening water molecule. Finally, the alpha-phosphate and uracil
      groups of UDP interact with R143 and R262 through intervening water molecules.
      The structure of LpxC complexed with pyrophosphate reveals generally similar
      intermolecular interactions in the basic patch. Unexpectedly, diphosphate binding
      in both complexes is accompanied by coordination to an additional zinc ion,
      resulting in the identification of a new metal-binding site termed the E-site.
      The structures of the LpxC-UDP and LpxC-pyrophosphate complexes provide new
      insights with regard to substrate recognition in the basic patch and metal ion
      coordination in the active site of LpxC.

PMID- 17176044
TI  - A parallel coiled-coil tetramer with offset helices.
AB  - Specific helix-helix interactions are fundamental in assembling the native state
      of proteins and in protein-protein interfaces. Coiled coils afford a unique model
      system for elucidating principles of molecular recognition between alpha helices.
      The coiled-coil fold is specified by a characteristic seven amino acid repeat
      containing hydrophobic residues at the first (a) and fourth (d) positions.
      Nonpolar side chains spaced three and four residues apart are referred to as the
      3-4 hydrophobic repeat. The presence of apolar amino acids at the e or g
      positions (corresponding to a 3-3-1 hydrophobic repeat) can provide new
      possibilities for close-packing of alpha-helices that includes examples such as
      the lac repressor tetramerization domain. Here we demonstrate that an
      unprecedented coiled-coil interface results from replacement of three charged
      residues at the e positions in the dimeric GCN4 leucine zipper by nonpolar valine
      side chains. Equilibrium circular dichroism and analytical ultracentrifugation
      studies indicate that the valine-containing mutant forms a discrete alpha-helical
      tetramer with a significantly higher stability than the parent leucine-zipper
      molecule. The 1.35 A resolution crystal structure of the tetramer reveals a
      parallel four-stranded coiled coil with a three-residue interhelical offset. The
      local packing geometry of the three hydrophobic positions in the tetramer
      conformation is completely different from that seen in classical tetrameric
      structures yet bears resemblance to that in three-stranded coiled coils. These
      studies demonstrate that distinct van der Waals interactions beyond the a and d
      side chains can generate a diverse set of helix-helix interfaces and three
      dimensional supercoil structures.

PMID- 17176045
TI  - Mechanism of dihydroneopterin aldolase: functional roles of the conserved active
      site glutamate and lysine residues.
AB  - Dihydroneopterin aldolase (DHNA) catalyzes the conversion of 7,8-dihydroneopterin
      (DHNP) to 6-hydroxymethyl-7,8-dihydropterin (HP) in the folate biosynthetic
      pathway. There are four conserved active site residues at the active site, E22,
      Y54, E74, and K100 in Staphylococcus aureus DHNA (SaDHNA), corresponding to E21,
      Y53, E73, and K98, respectively, in Escherichia coli DHNA (EcDHNA). The
      functional roles of the conserved glutamate and lysine residues have been
      investigated by site-directed mutagenesis in this work. E22 and E74 of SaDHNA and
      E21, E73, and K98 of EcDHNA were replaced with alanine. K100 of SaDHNA was
      replaced with alanine and glutamine. The mutant proteins were characterized by
      equilibrium binding, stopped-flow binding, and steady-state kinetic analyses. For
      SaDHNA, none of the mutations except E74A caused dramatic changes in the
      affinities of the enzyme for the substrate or product analogues or the rate
      constants. The Kd values for SaE74A were estimated to be >3000 microM, suggesting
      that the Kd values of the mutant are at least 100 times those of the wild-type
      enzyme. For EcDHNA, the E73A mutation increased the Kd values for the substrate
      or product analogues neopterin (MP), monapterin (NP), and 6-hydroxypterin (HPO)
      by factors of 340, 160, and 5600, respectively, relative to those of the wild
      type enzyme. The K98A mutation increased the Kd values for NP, MP, and HPO by
      factors of 14, 3.6, and 230, respectively. The E21A mutation increased the Kd
      values for NP and HPO by factors of 2.2 and 42, respectively, but decreased the
      Kd value for MP by a factor of 3.3. The E22 (E21) and K100 (K98) mutations
      decreased the kcat values by factors of 1.3-2 x 10(4). The E74 (E73) mutation
      decreased in the kcat values by factors of approximately 10. The results
      suggested that E74 of SaDHNA and E73 of EcDHNA are important for substrate
      binding, but their roles in catalysis are minor. In contrast, E22 and K100 of
      SaDHNA are important for catalysis, but their roles in substrate binding are
      minor. On the other hand, E21 and K98 of EcDHNA are important for both substrate
      binding and catalysis.

PMID- 17176046
TI  - Catalytic mechanism and molecular recognition of E. coli UDP-3-O-(R-3
      hydroxymyristoyl)-N-acetylglucosamine deacetylase probed by mutagenesis.
AB  - UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a metal
      dependent deacetylase that catalyzes the hydrolysis of UDP-3-O-myristoyl-N-acetyl
      glucosamine to form UDP-3-O-myristoyl-glucosamine and acetate. This is the
      committed step in the biosynthesis of lipid A, and therefore, LpxC is a target
      for the development of antimicrobial agents in the treatment of Gram-negative
      infections. To facilitate the development of potent and specific inhibitors of
      LpxC, the molecular determinants of binding and specificity and the catalytic
      mechanism for this enzyme have been probed. The functions of active site residues
      have been classified on the basis of changes in steady-state turnover (kcat, KM,
      and kcat/KM) and product binding affinity (KDProduct). We have identified side
      chains that enhance product affinity and reactivity (F192, K239, D246, and H265),
      destabilize product affinity (E78 and D197), and preferentially enhance catalytic
      efficiency (H19, T19, K143, and N162). In addition, the affinity of LpxC for
      myrUDP-GlcNH2 is dependent on two ionizations, one deprotonation and one
      protonation, with apparent pKa values of 6.5 +/- 0.1 and 7.4 +/- 0.1,
      respectively. The UDP moiety of the product contributes significantly to
      recognition by LpxC, suggesting that this region can be targeted in drug
      development. These data provide a map of the active site features essential for
      catalysis and molecular recognition by LpxC that can be used for developing more
      potent LpxC inhibitors.

PMID- 17176047
TI  - Cancer-associated glycoforms of gelatinase B exhibit a decreased level of binding
      to galectin-3.
AB  - Gelatinase B (MMP-9) and galectin-3 are widely known to participate in tumor cell
      invasion and metastasis. Glycans derived from MMP-9 expressed in MCF-7 breast
      cancer and THP-1 myeloid leukemia cells were compared with those from MMP-9
      expressed in natural neutrophils. The many O-linked glycans of neutrophil
      gelatinase B presented a cluster of mainly galactosylated core II structures, 46%
      of which were ligands for galectin-3; 11% contained two to three N
      acetyllactosamine repeating units that are high-affinity ligands for the lectin.
      The glycan epitopes thus provide MMP-9 with both high-affinity and (presumably)
      high-avidity interactions with galectin-3. In contrast, the O-glycans released
      from MMP-9 expressed in MCF-7 and THP-1 cells were predominantly sialylated core
      I structures. Only 10% of MCF-7 and THP-1 gelatinase B O-glycans were ligands for
      galectin-3 and contained only a maximum single N-acetyllactosamine repeat.
      Consistent with the glycan analysis, surface plasmon resonance binding assays
      indicated that the cancer-associated glycoforms of MMP-9 bound galectin-3 with an
      affinity and avidity significantly reduced compared with those of the natural
      neutrophil MMP-9. Galectin-3 exists as a multimer that also binds laminin,
      providing a means of localizing neutrophil MMP-9 in the extracellular matrix
      (ECM). The analytical data presented here suggest that MMP-9 glycoforms secreted
      by tumor cells are unlikely to be tethered at the site of secretion, thus
      promoting more extensive cleavage of the ECM and providing a rationale for the
      contribution that gelatinase B makes to cancer cell metastasis.

PMID- 17176048
TI  - Assembly of bacteriophage lambda terminase into a viral DNA maturation and
      packaging machine.
AB  - Terminase enzymes are common to complex double-stranded DNA viruses and function
      to package viral DNA into the capsid. We recently demonstrated that the
      bacteriophage lambda terminase gpA and gpNu1 proteins assemble into a stable
      heterotrimer with a molar ratio gpA1/gpNu1(2). This terminase protomer possesses
      DNA maturation and packaging activities that are dependent on the E. coli
      integration host factor protein (IHF). Here, we show that the protomer further
      assembles into a homogeneous tetramer of protomers of composition
      (gpA1/gpNu1(2))4. Electron microscopy shows that the tetramer forms a ring
      structure large enough to encircle duplex DNA. In contrast to the heterotrimer,
      the ring tetramer can mature and package viral DNA in the absence of IHF. We
      propose that IHF induced bending of viral DNA facilitates the assembly of four
      terminase protomers into a ring tetramer that represents the catalytically
      competent DNA maturation and packaging complex in vivo. This work provides, for
      the first time, insight into the functional assembly state of a viral DNA
      packaging motor.

PMID- 17176049
TI  - Entropic folding pathway of human epidermal growth factor explored by disulfide
      scrambling and amplified collective motion simulations.
AB  - Epidermal growth factor (EGF) regulates cell proliferation and differentiation by
      binding to the EGF receptor (EGFR) extra-cellular domains. Human EGF is a small,
      single-chain protein comprising three distinct loops (A, B, and C), which are
      connected by three disulfide bridges (Cys6-Cys20, Cys14-Cys31, and Cys33-Cys42).
      These disulfide bridges are essential for structural stability and biological
      activity. EGF was extensively studied by disulfide scrambling, an experimental
      technique for the conformational entrapment of intermediate states, which allows
      us to study the folding pathway of proteins containing disulfide bonds. The
      experimental results showed that there is a major 2-disulfide intermediate
      (denoted EGF-II) and that the native disulfide bonding pattern is less prevalent
      in one of the mutants. In this article, we investigated for the first time the
      solution conformations of wild-type EGF, EGF-II, and the mutant S9C through
      extensive molecular dynamics (MD) simulations in water using both the standard MD
      technique and a recently developed amplified-collective-motion (ACM) sampling
      method. Compared to standard MD simulations, we achieved a much more enhanced
      sampling by the ACM simulations, and the structures were sufficiently relaxed to
      estimate configurational entropies. The simulation results suggest a
      predominantly entropic folding pathway governed by the disorder of three
      functional loop regions. Although EGF-II exhibits two native disulfide bonds
      (Cys14-Cys31 and Cys33- Cys42), its large configurational entropy inhibits a
      direct transition to the native structure in the folding process. When Ser9 is
      mutated into Cys, a non-native disulfide bridge Cys9- Cys20 is slightly more
      favorable than the native Cys6-Cys20 because a less constrained N-terminus
      affords larger entropy. Isomers that are functionally less active also exhibit a
      more localized dynamics of the functional loop regions, which may suggest a
      possible mechanism for the modulation of EGF activity.

PMID- 17176051
TI  - Conformational flexibility, hydration and state parameter fluctuations of
      fibroblast growth factor-10: effects of ligand binding.
AB  - Differential effects of ligand binding on local and global fibroblast growth
      factor-10 (FGF-10) flexibility and stability have been investigated utilizing a
      variety of experimental and computational techniques. Normal mode analysis was
      used to predict the low frequency motions and regional flexibility of FGF-10.
      Similarly, regional variations in local folding/unfolding equilibria were
      characterized with the COREX/BEST algorithm. Experimental adiabatic and
      isothermal compressibilities of FGF-10 alone and in the presence of polyanions
      are compared. Furthermore, the effect of polyanions on the coefficient of thermal
      expansion is compared. Measurements of density, heat capacity, compressibility,
      and expansibility were combined to calculate experimentally determined volume and
      enthalpy fluctuations. Global effects of polyanions on FGF-10 flexibility,
      thermodynamic fluctuations, and hydration vary depending on the size and charge
      density of the polyanion. Local effects of polyanions were investigated utilizing
      time-resolved fluorescence spectroscopy and red edge excitation spectroscopy
      (REES). Increased rigidity of the protein matrix or an increased solvent response
      surrounding the Trp residues is observed in the presence of polyanions.
      Similarly, time-resolved spectroscopy reveals increased ground state
      heterogeneity and increased dipole relaxation on the time scale of fluorescence
      for FGF-10 in the presence of polyanions. These polyanions increase
      heterogeneity, global flexibility, and fluctuations while increasing the melting
      temperature (Tm) of FGF-10.

PMID- 17176050
TI  - Direct sugar binding to LacY measured by resonance energy transfer.
AB  - Trp151 in the lactose permease of Escherichia coli (LacY) is an important
      component of the sugar-binding site and the only Trp residue out of six that is
      in close proximity to the galactopyranoside in the structure (1PV7). The short
      distance between Trp151 and the sugar is favorable for Forster resonance energy
      transfer (FRET) to nitrophenyl or dansyl derivatives with the fluorophore at the
      anomeric position of galactose. Modeling of 4-nitrophenyl-alpha-d
      galactopyranoside (alpha-NPG) in the binding-site of LacY places the nitrophenyl
      moiety about 12 A away from Trp151, a distance commensurate with the Forster
      distance for a Trp-nitrobenzoyl pair. We demonstrate here that alpha-NPG binding
      to LacY containing all six native Trp residues causes galactopyranoside-specific
      FRET from Trp151. Moreover, binding of alpha-NPG is sufficiently slow to resolve
      time-dependent fluorescence changes by stopped-flow. The rate of change in Trp -
      > alpha-NPG FRET is linearly dependent upon sugar concentration, which allows
      estimation of kinetic parameters for binding. Furthermore, 2-(4'
      maleimidylanilino)naphthalene-6-sulfonic acid (MIANS) covalently attached to the
      cytoplasmic end of helix X is sensitive to sugar binding, reflecting a ligand
      induced conformational change. Stopped-flow kinetics of Trp --> alpha-NPG FRET
      and sugar-induced changes in MIANS fluorescence in the same protein reveal a two
      step process: a relatively rapid binding step detected by Trp151 --> alpha-NPG
      FRET followed by a slower conformational change detected by a change in MIANS
      fluorescence.

PMID- 17176052
TI  - Mutagenesis and modeling of the peroxiredoxin (Prx) complex with the NMR
      structure of ATP-bound human sulfiredoxin implicate aspartate 187 of Prx I as the
      catalytic residue in ATP hydrolysis.
AB  - The catalytic cysteine of certain members of the peroxiredoxin (Prx) family can
      be hyperoxidized to cysteinesulfinic acid during reduction of peroxides.
      Sulfiredoxin is responsible for the ATP-dependent reduction of cysteinesulfinic
      acid (SO2H) of hyperoxidized Prx. Here we report the NMR solution structure of
      human sulfiredoxin (hSrx), both with and without bound ATP, and we model the
      complex of ATP-bound hSrx with Prx. Binding ATP causes only small changes in the
      NMR structure of hSrx, and the bound ATP conformation is quite similar to that
      seen for the previously reported X-ray structure of the ADP-hSrx complex.
      Although hSrx binds ATP, it does not catalyze hydrolysis by itself and has no
      catalytic acid residue typical of most ATPase and kinase family proteins. For
      modeling the complex, the ATP-bound hSrx was docked to hyperoxidized Prx II using
      EMAP of CHARMM. In the model complex, Asn186 of Prx II (Asp187 of Prx I) is in
      contact with the hSrx-bound ATP beta- and gamma-phosphate groups. Asp187 of Prx I
      was mutated to alanine and asparagine, and binding and activity of the mutants
      with hSrx were compared to those of the wild type. For the D187N mutant, both
      binding and hydrolysis and reduction activities were comparable to those of the
      wild type, whereas for D187A, binding was unimpaired but ATP hydrolysis and
      reduction did not occur. The modeling and mutagenesis analyses strongly implicate
      Asp187 of Prx I as the catalytic residue responsible for ATP hydrolysis in the
      cysteinesulfinic acid reduction of Prx by hSrx.

PMID- 17176053
TI  - Accessibility of cysteine residues substituted into the cytoplasmic regions of
      the alpha-factor receptor identifies the intracellular residues that are
      available for G protein interaction.
AB  - The yeast alpha-factor pheromone receptor (Ste2) belongs to the family of G
      protein-coupled receptors (GPCRs) that contain seven transmembrane domains. To
      define the residues that are accessible to the cytoplasmic G protein, Cys
      scanning mutagenesis was carried out in which each of the residues that span the
      intracellular loops and the cytoplasmic end of transmembrane domain 7 was
      substituted with Cys. The 90 different Cys-substituted residues were then assayed
      for reactivity with MTSEA-biotin [[2
      [(biotinoyl)amino]ethyl]methanethiosulfonate], which reacts with solvent
      accessible sulfhydryl groups. As part of these studies we show that adding free
      Cys to stop the MTSEA-biotin reactions has potential pitfalls in that Cys can
      rapidly undergo disulfide exchange with the biotinylated receptor proteins at pH
      >or=7. The central regions of the intracellular loops of Ste2 were all highly
      accessible to MTSEA-biotin. Residues near the ends of the loops typically
      exhibited a drop in the level of reactivity over a consecutive series of residues
      that was inferred to be the membrane boundary. Interestingly, these boundary
      residues were enriched in hydrophobic residues, suggesting that they may form a
      hydrophobic pocket for interaction with the G protein. Comparison with
      accessibility data from a previous study of the extracellular side of Ste2
      indicates that the transmembrane domains vary in length, consistent with some
      transmembrane domains being tilted relative to the plane of the membrane as they
      are in rhodopsin. Altogether, these results define the residues that are
      accessible to the G protein and provide an important structural framework for the
      interpretation of the role of Ste2 residues that function in G protein
      activation.

PMID- 17176055
TI  - Allosteric and orthosteric binding modes of two nonpeptide human gonadotropin
      releasing hormone receptor antagonists.
AB  - Nonpeptide antagonists of the human gonadotropin-releasing hormone receptor (GnRH
      R) have been the subject of considerable interest because of their potential as a
      new class of oral therapeutics for the treatment of sex hormone-dependent
      diseases and infertility. While many classes of competitive GnRH-R antagonists
      have been described, we present here the first characterization of an allosteric
      nonpeptide GnRH-R antagonist. Previously, 5-(3,5,5,8,8-pentamethyl-5,6,7,8
      tetrahydronaphthalen-2-ylmethyl)furan-2-carboxylic acid (2,4,6
      trimethoxyphenyl)amide (here called Furan-1) had been demonstrated to be a potent
      GnRH-R antagonist both in vitro and in vivo. Using mutagenesis, the binding sites
      for Furan-1 and another potent nonpeptide antagonist (NBI-42902) have been mapped
      and are shown to be adjacent but nonoverlapping. Furan-1 is shown to affect the
      binding kinetics of radiolabeled peptide agonists as well as radiolabeled NBI
      42902, and the kinetic data fit the allosteric ternary complex model. Furan-1 is
      considerably negatively cooperative with the nonpeptide antagonist and extremely
      negatively cooperative with the peptide agonist [125I-His5,d-Tyr6]GnRH so that it
      is nearly indistinguishable from an orthosteric competitive compound. Taken
      together, these data were used to develop a model of the nonpeptides bound to the
      GnRH-R binding site consistent with the current data.

PMID- 17176054
TI  - Dissecting the mechanism of Epac activation via hydrogen-deuterium exchange FT-IR
      and structural modeling.
AB  - Exchange proteins directly activated by cAMP (Epac) make up a family of cAMP
      binding domain-containing proteins that play important roles in mediating the
      effects of cAMP through the activation of downstream small GTPases, Ras-proximate
      proteins. To delineate the mechanism of Epac activation, we probed the
      conformation and structural dynamics of Epac using amide hydrogen-deuterium (H-D)
      exchange coupled with Fourier transform infrared spectroscopy (FT-IR) and
      structural modeling. Our studies show that unlike that of cAMP-dependent protein
      kinase (PKA), the classic intracellular cAMP receptor, binding of cAMP to Epac
      does not induce significant changes in overall secondary structure and structural
      dynamics, as measured by FT-IR and the rate of H-D exchange, respectively. These
      results suggest that Epac activation does not involve significant changes in the
      amount of exposed surface areas as in the case of PKA activation, and
      conformational changes induced by cAMP in Epac are most likely confined to small
      local regions. Homology modeling and comparative structural analyses of the CBDs
      of Epac and PKA lead us to propose a model of Epac activation. On the basis of
      our model, Epac activation by cAMP employs the same underlying structural
      principal utilized by PKA, although the detailed structural and conformational
      changes associated with Epac and PKA activation are significantly different. In
      addition, we predict that during Epac activation the first beta-strand of the
      switchboard switches its conformation to a alpha-helix, which folds back to the
      beta-barrel core of the CBD and interacts directly with cAMP to form the base of
      the cAMP-binding pocket.

PMID- 17176056
TI  - Structural requirements of FGF-1 for receptor binding and translocation into
      cells.
AB  - FGF-1 binds to and activates specific transmembrane receptors (FGFRs) and is
      subsequently internalized and translocated to the interior of the cell. To
      elucidate the role of the receptor in the translocation process, we studied the
      effects of the elimination of distinct sites of the ligand-receptor interaction.
      On the basis of the structure of the FGF-1-FGFR1 complex, we substituted four key
      amino acid residues of FGF-1 from the FGF-receptor binding site with alanines,
      constructing four point mutants and one double mutant. We determined by in vivo
      assays in NIH 3T3 cells the ability of the mutants to bind to specific FGF
      receptors, to stimulate DNA synthesis, and to activate downstream signaling
      pathways. We found that correct binding to the receptor is necessary for optimal
      stimulation of DNA synthesis. All four single mutants became phosphorylated to
      different extents, indicating that they were translocated to the cytosol/nucleus
      with varying efficiency. This indicates that despite a low affinity for FGFR,
      translocation to the cytosol/nucleus can still occur. However, simultaneous
      substitution in two of the positions led to a total loss of biological activity
      of the growth factor and prevented its internalization, implying that there is
      only one strongly receptor-dependent, productive way of translocating FGF-1. We
      also found that the process of translocation did not correlate with the thermal
      stability of the protein. Additionally, we observed a clear negative correlation
      between the stability of the FGF-1 mutants and the efficiency of their
      phosphorylation, which strongly suggests that protein kinases prefer the unfolded
      state of the protein substrate.

PMID- 17176057
TI  - Conformational coupling between the cytoplasmic carboxylic acid and the retinal
      in a fungal light-driven proton pump.
AB  - Many fungal rhodopsins, eukaryotic structural homologues of the archaeal light
      driven proton pump bacteriorhodopsin, have been discovered in the course of
      genome sequencing projects. Recently, two fungal rhodopsins were characterized in
      vitro and exhibited very different photochemical behavior. Neurospora rhodopsin
      possesses a slow photocycle and shows no ion transport, reminiscent of sensory
      rhodopsins, while Leptosphaeria rhodopsin has a fast bacteriorhodopsin-like
      photocycle and pumps protons light-dependently. Such a dramatic difference is
      surprising considering the very high degree of sequence homology of the two
      proteins. In this paper, we investigate whether the chemical structure of a
      cytoplasmic carboxylic acid, the homologue of Asp-96 of bacteriorhodopsin serving
      as a proton donor for the retinal Schiff base, can define the photochemical
      properties of fungal rhodopsins. We studied mutants of Leptosphaeria rhodopsin in
      which this aspartic acid was replaced with Glu or Asn using spectroscopy in the
      infrared and visible ranges. We show that Glu at this position is inefficient as
      a proton donor similar to a nonprotonatable Asn. Moreover, this replacement
      induces long-range structural perturbations of the retinal environment, as
      evidenced by changes in the vibrational bands of retinal (especially, hydrogen
      out-of-plane modes) and neighboring aspartic acids and water molecules. The
      conformational coupling of the mutation site to the retinal may be mediated by
      helical rearrangements as suggested by the changes in amide and proline
      vibrational bands. We conclude that the difference in the photochemical behavior
      of fungal rhodopsins from Leptosphaeria and Neurospora may be ascribed, to some
      extent, to the replacement of the cytoplasmic proton donor Asp with Glu.

PMID- 17176060
TI  - Identification of the C=O stretching vibrations of FMN and peptide backbone by
      13C-labeling of the LOV2 domain of Adiantum phytochrome3.
AB  - Phototropin, a blue-light photoreceptor in plants, has two FMN-binding domains
      named LOV1 and LOV2. We previously observed temperature-dependent FTIR spectral
      changes in the C=O stretching region (amide-I vibrational region of the peptide
      backbone) for the LOV2 domain of Adiantum phytochrome3 (phy3-LOV2), suggesting
      progressive structural changes in the protein moiety (Iwata, T., Nozaki, D.,
      Tokutomi, S., Kagawa, T., Wada, M., and Kandori, H. (2003) Biochemistry 42, 8183
      8191). Because FMN also possesses two C=O groups, in this article, we aimed at
      assigning C=O stretching vibrations of the FMN and protein by using 13C-labeling.
      We assigned the C(4)=O and C(2)=O stretching vibrations of FMN by using [4,10a
      13C2] and [2-13C] FMNs, respectively, whereas C=O stretching vibrations of amide
      I were assigned by using 13C-labeling of protein. We found that both C(4)=O and
      C(2)=O stretching vibrations shift to higher frequencies upon the formation of
      S390 at 77-295 K, suggesting that the hydrogen bonds of the C=O groups are
      weakened by adduct formation. Adduct formation presumably relocates the FMN
      chromophore apart from its hydrogen-bonding donors. Temperature-dependent amide-I
      bands are unequivocally assigned by separating the chromophore bands. The
      hydrogen bond of the peptide backbone in the loop region is weakened upon S390
      formation at low temperatures, while being strengthened at room temperature. The
      hydrogen bond of the peptide backbone in the alpha-helix is weakened regardless
      of temperature. On the other hand, structural perturbation of the beta-sheet is
      observed only at room temperature, where the hydrogen bond is strengthened. Light
      signal transduction by phy3-LOV2 must be achieved by the progressive protein
      structural changes initiated by the adduct formation of the FMN.

PMID- 17176059
TI  - Metal-binding and nuclease activity of an antimicrobial peptide analogue of the
      salivary histatin 5.
AB  - The salivary antimicrobial peptide histatin 5 is characterized by its cationic
      nature, structural flexibility, and the presence of two metal-binding sites (the
      ATCUN motif and a Zn-binding motif). These properties make this peptide a good
      model for the design of new drugs of low molecular weight. In this work, we have
      synthesized and studied a new peptide, an analogue of the histatin 5 named ATCUN
      C16, which contains both metal-binding centers. The results show that our 20
      residue-derived peptide preserves anticandidal activity and exhibits a higher
      propensity to assume a stable conformation in a hydrophobic environment than do
      histatin 5 and the C16 peptide that contains the 16 residues of the C-terminal
      part of histatin 5, although overall our peptide remains a flexible molecule.
      ACTUN-C16 was found to bind DNA in a gel retardation assay and to have a nuclease
      activity in the presence of copper and zinc ions and ascorbate. Its nuclease
      activity can be attributed to the synergistic action of oxidative and hydrolytic
      activities due to the Cu-ATCUN complex and to the zinc ion coordination,
      respectively. The results show a new property of this family of salivary peptides
      and suggest a novel use of this peptide as a small nuclease and biotechnological
      tool.

PMID- 17176058
TI  - Metal binding studies and EPR spectroscopy of the manganese transport regulator
      MntR.
AB  - Manganese transport regulator (MntR) is a member of the diphtheria toxin
      repressor (DtxR) family of transcription factors that is responsible for
      manganese homeostasis in Bacillus subtilis. Prior biophysical studies have
      focused on the metal-mediated DNA binding of MntR [Lieser, S. A., Davis, T. C.,
      Helmann, J. D., and Cohen, S. M. (2003) Biochemistry 42, 12634-12642], as well as
      metal stabilization of the MntR structure [Golynskiy, M. V., Davis, T. C.,
      Helmann, J. D., and Cohen, S. M. (2005) Biochemistry 44, 3380-3389], but only
      limited data on the metal-binding affinities for MntR are available. Herein, the
      metal-binding affinities of MntR were determined by using electron paramagnetic
      resonance (EPR) spectroscopy, as well as competition experiments with the
      fluorimetric dyes Fura-2 and Mag-fura-2. MntR was not capable of competing with
      Fura-2 for the binding of transition metal ions. Therefore, the metal-binding
      affinities and stoichiometries of Mag-fura-2 for Mn2+, Co2+, Ni2+, Zn2+, and Cd2+
      were determined and utilized in MntR/Mag-fura-2 competition experiments. The
      measured Kd values for MntR metal binding are comparable to those reported for
      DtxR metal binding [Kd from 10(-)7 to 10(-4) M; D'Aquino, J. A., et al. (2005)
      Proc. Natl. Acad. Sci. U.S.A. 102, 18408-18413], AntR [a homologue from Bacillus
      anthracis; Sen, K. I. et al. (2006) Biochemistry 45, 4295-4303], and generally
      follow the Irving-Williams series. Direct detection of the dinuclear Mn2+ site in
      MntR with EPR spectroscopy is presented, and the exchange interaction was
      determined, J = -0.2 cm-1. This value is lower in magnitude than most known
      dinuclear Mn2+ sites in proteins and synthetic complexes and is consistent with a
      dinuclear Mn2+ site with a longer Mn...Mn distance (4.4 A) observed in some of
      the available crystal structures. MntR is found to have a surprisingly low
      binding affinity (approximately 160 microM) for its cognate metal ion Mn2+.
      Moreover, the results of DNA binding studies in the presence of limiting metal
      ion concentrations were found to be consistent with the measured metal-binding
      constants. The metal-binding affinities of MntR reported here help to elucidate
      the regulatory mechanism of this metal-dependent transcription factor.

PMID- 17176061
TI  - X-ray structure of a hydroxylase-regulatory protein complex from a hydrocarbon
      oxidizing multicomponent monooxygenase, Pseudomonas sp. OX1 phenol hydroxylase.
AB  - Phenol hydroxylase (PH) belongs to a family of bacterial multicomponent
      monooxygenases (BMMs) with carboxylate-bridged diiron active sites. Included are
      toluene/o-xylene (ToMO) and soluble methane (sMMO) monooxygenase. PH hydroxylates
      aromatic compounds, but unlike sMMO, it cannot oxidize alkanes despite having a
      similar dinuclear iron active site. Important for activity is formation of a
      complex between the hydroxylase and a regulatory protein component. To address
      how structural features of BMM hydroxylases and their component complexes may
      facilitate the catalytic mechanism and choice of substrate, we determined X-ray
      structures of native and SeMet forms of the PH hydroxylase (PHH) in complex with
      its regulatory protein (PHM) to 2.3 A resolution. PHM binds in a canyon on one
      side of the (alphabetagamma)2 PHH dimer, contacting alpha-subunit helices A, E,
      and F approximately 12 A above the diiron core. The structure of the dinuclear
      iron center in PHH resembles that of mixed-valent MMOH, suggesting an
      Fe(II)Fe(III) oxidation state. Helix E, which comprises part of the iron
      coordinating four-helix bundle, has more pi-helical character than analogous E
      helices in MMOH and ToMOH lacking a bound regulatory protein. Consequently,
      conserved active site Thr and Asn residues translocate to the protein surface,
      and an approximately 6 A pore opens through the four-helix bundle. Of likely
      functional significance is a specific hydrogen bond formed between this Asn
      residue and a conserved Ser side chain on PHM. The PHM protein covers a putative
      docking site on PHH for the PH reductase, which transfers electrons to the PHH
      diiron center prior to O2 activation, suggesting that the regulatory component
      may function to block undesired reduction of oxygenated intermediates during the
      catalytic cycle. A series of hydrophobic cavities through the PHH alpha-subunit,
      analogous to those in MMOH, may facilitate movement of the substrate to and/or
      product from the active site pocket. Comparisons between the ToMOH and PHH
      structures provide insights into their substrate regiospecificities.

PMID- 17176063
TI  - Matrix metalloproteinase-1 takes advantage of the induced fit mechanism to cleave
      the triple-helical type I collagen molecule.
AB  - The collagenases are members of the matrix metalloproteinase family (MMP) that
      degrade native triple-helical type I collagen. To understand the mechanism by
      which these enzymes recognize and cleave this substrate, we studied the substrate
      specificity of a modified form of MMP-1 (FC) in which its active site region
      (amino acids 212-254) had been replaced with that of MMP-9 (amino acids 395-437).
      Although this substitution increased the activity of the enzyme toward gelatin
      and the peptide substrate Mca-PLGL(Dpa)AR-NH2 by approximately 3- and
      approximately 11-fold, respectively, it decreased the type I collagenolytic
      activity of the enzyme to 0.13%. The replacement of Gly233, the only amino acid
      in this region of FC that is conserved in all collagenase family members, with
      the corresponding Glu residue in MMP-9 resulted in a substantial decrease in the
      type I collagenolytic activity of the enzyme without affecting its general
      proteolytic activities. The kinetic parameters of the FC/G233E mutant for the
      collagen substrate were similar to those of the chimeric enzyme. In addition,
      substituting Gly233 for Glu in the chimera increased the collagenolytic activity
      of the enzyme by 12-fold. Interestingly, replacing Glu415 in MMP-9 with Gly, its
      corresponding residue in FC, endowed the enzyme with type I collagenolytic
      activity. The catalytic activity of the MMP-9 mutant toward triple-helical type I
      collagen was 2-fold higher than that of the collagenase chimera. These data in
      conjunction with the X-ray crystal structure of FC indicate that Gly233 provides
      the flexibility necessary for the enzyme active site to change conformation upon
      substrate binding. The flexibility provided by the Gly residue is essential for
      type I collagenolytic activity.

PMID- 17176062
TI  - Evolutionary migration of a post-translationally modified active-site residue in
      the proton-pumping heme-copper oxygen reductases.
AB  - In the respiratory chains of aerobic organisms, oxygen reductase members of the
      heme-copper superfamily couple the reduction of O2 to proton pumping, generating
      an electrochemical gradient. There are three distinct families of heme-copper
      oxygen reductases: A, B, and C types. The A- and B-type oxygen reductases have an
      active-site tyrosine that forms a unique cross-linked histidine-tyrosine
      cofactor. In the C-type oxygen reductases (also called cbb3 oxidases), an
      analogous active-site tyrosine has recently been predicted by molecular modeling
      to be located within a different transmembrane helix in comparison to the A- and
      B-type oxygen reductases. In this work, Fourier-transform mass spectrometry is
      used to show that the predicted tyrosine forms a histidine-tyrosine cross-linked
      cofactor in the active site of the C-type oxygen reductases. This is the first
      known example of the evolutionary migration of a post-translationally modified
      active-site residue. It also verifies the presence of a unique cofactor in all
      three families of proton-pumping respiratory oxidases, demonstrating that these
      enzymes likely share a common reaction mechanism and that the histidine-tyrosine
      cofactor may be a required component for proton pumping.

PMID- 17176065
TI  - Comparative oxidation studies of methionine residues reflect a structural effect
      on chemical kinetics in rhG-CSF.
AB  - The effect of protein conformation on the rate of chemical degradation is poorly
      understood. To address the role of structure on chemical degradation kinetics,
      comparative oxidation studies of methionine residues in recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) were performed. The kinetics of
      oxidation of methionine residues by hydrogen peroxide (H2O2) in rhG-CSF and
      corresponding chemically synthesized peptides thereof was measured at different
      temperatures. To assess structural effects, equilibrium denaturation experiments
      also were conducted on rhG-CSF, yielding the free energy of unfolding as a
      function of temperature. A comparison of the relative rates of oxidation of
      methionine residues in short peptides with those of corresponding methionine
      residues in rhG-CSF yields an understanding of how protein tertiary structure
      affects oxidation reactions. For the temperature range that was studied, 4-45
      degrees C, the oxidation rate constants followed an Arrhenius equation quite
      well, suggesting the lack of temperature-induced local structural perturbations
      that affect chemical degradation rates. One of the four methionine residues, Met
      122, exhibited an activation energy significantly different from that of the
      corresponding peptide. Extrapolation of kinetic data predicts non-Arrhenius
      behavior around the melting temperature. Three phenomenological models based on
      different mechanisms are discussed, and an application to shelf life prediction
      of pharmaceuticals is presented.

PMID- 17176064
TI  - The catalytic role of the copper ligand H172 of peptidylglycine alpha
      hydroxylating monooxygenase: a kinetic study of the H172A mutant.
AB  - An essential histidine ligand to the electron transfer copper (CuH) of
      peptidylglycine alpha-hydroxylating monooxygenase (PHMcc) was mutated to an
      alanine and found to retain copper binding and hydroxylase activity [Jaron, S.,
      et al. (2002) Biochemistry 41, 13274-13282]. An extensive kinetic and deuterium
      isotope effect study finds this mutant to maintain full coupling of O2 consumed
      to product formed despite a 3 order-of-magnitude decrease in kcat and a 300-fold
      decrease in kcat/Km(O2). Unexpectedly, electron transfer is not rate-limiting in
      H172A. Rather, the increased kinetic isotope effect (KIE) on kcat of 3.27 +/-
      0.39 suggests that C-H bond cleavage has become more rate-limiting, implicating a
      role for His172 that goes beyond that of a simple ligand to CuH. The mechanistic
      implications are discussed.

PMID- 17176066
TI  - In vitro biosynthesis of violacein from L-tryptophan by the enzymes VioA-E from
      Chromobacterium violaceum.
AB  - The purple chromobacterial pigment violacein arises by enzymatic oxidation and
      coupling of two molecules of l-tryptophan to give a rearranged pyrrolidone
      containing scaffold in the final pigment. We have purified five contiguously
      encoded proteins VioA-E after expression in Escherichia coli and demonstrate the
      full 14-electron oxidation pathway to yield the final chromophore. The
      flavoenzyme VioA and the heme protein VioB work in conjunction to oxidize and
      dimerize l-tryptophan to a nascent product that can default to the off pathway
      metabolite chromopyrrolic acid. In the presence of VioE, the intermediate instead
      undergoes on-pathway [1,2] indole rearrangement to prodeoxyviolacein. The last
      two enzymes in the pathway are flavin-dependent oxygenases, VioC and VioD, that
      act sequentially. VioD hydroxylates one indole ring at the 5-position to yield
      proviolacein, and VioC then acts on the other indole ring at the 2-position to
      create the oxindole and complete violacein formation.

PMID- 17176067
TI  - Mapping the dimer interface in the C-terminal domains of the yeast MLH1-PMS1
      heterodimer.
AB  - Yeast MutLalpha is a heterodimer of MLH1 and PMS1 that participates in a variety
      of DNA transactions, including DNA mismatch repair. Formation of the MutLalpha
      heterodimer requires that the C-terminal domains of MLH1 and PMS1 interact in a
      manner that is not yet fully understood. Here we investigate the interactions
      involved in heterodimerization. Using protein surface modification and mass
      spectrometry, we identify numerous lysine residues that are exposed to solvent in
      monomeric MLH1. A corresponding analysis of the MLH1-PMS1 heterodimer reveals
      that three of these exposed residues, K665, K675, and K704, are no longer solvent
      accessible in the heterodimer, suggesting that they are within the dimer
      interface. We refine secondary structure predictions and sequence alignments of C
      terminal residues of seven eukaryotic MutL homologues and then develop homology
      models for the N- and C-terminal domains of MLH1. On the basis of this
      information, we present a model for interaction of the C-terminal domains of MLH1
      and PMS1.

PMID- 17176068
TI  - Proline scanning mutagenesis reveals non-native fold in the molten globule state
      of equine beta-lactoglobulin.
AB  - The secondary structure in the molten globule state (an equilibrium analogue of a
      burst-phase folding intermediate) of equine beta-lactoglobulin was investigated
      by changes in the circular dichroic spectrum induced by a series of site-directed
      proline substitutions. The results challenge the structural picture obtained from
      previous hydrogen/deuterium exchange experiments. A stable non-native alpha-helix
      was found to exist in the region corresponding to the eighth strand (H strand) in
      the native structure, where the backbone amide protons are the most strongly
      protected from exchange. Therefore, the backbone topology in the folding core is
      significantly different from that in the native structure. This indicates that
      the burst-phase folding intermediate of beta-lactoglobulin is a trapped species
      because of misfolded backbone topology.

PMID- 17176069
TI  - Cathepsin D propeptide: mechanism and regulation of its interaction with the
      catalytic core.
AB  - Propeptide blocks the active site in the inactive zymogen of cathepsin D and is
      cleaved off during zymogen activation. We have designed a set of peptidic
      fragments derived from the propeptide structure and evaluated their inhibitory
      potency against mature cathepsin D using a kinetic assay. Our mapping of the
      cathepsin D propeptide indicated two domains in the propeptide involved in the
      inhibitory interaction with the enzyme core: the active site "anchor" domain and
      the N-terminus of the propeptide. The latter plays a dominant role in propeptide
      inhibition (nanomolar Ki), and its high-affinity binding was corroborated by
      fluorescence polarization measurements. In addition to the inhibitory domains of
      propeptide, a fragment derived from the N-terminus of mature cathepsin D
      displayed inhibition. This finding supports its proposed regulatory function. The
      interaction mechanisms of the identified inhibitory domains were characterized by
      determining their modes of inhibition as well as by spatial modeling of the
      propeptide in the zymogen molecule. The inhibitory interaction of the N-terminal
      propeptide domain was abolished in the presence of sulfated polysaccharides,
      which interact with basic propeptide residues. The inhibitory potency of the
      active site anchor domain was affected by the Ala38pVal substitution, a
      propeptide polymorphism reported to be associated with the pathology of
      Alzheimer's disease. We infer that propeptide is a sensitive tethered ligand that
      allows for complex modulation of cathepsin D zymogen activation.

PMID- 17176070
TI  - Functional role of the conserved active site proline of triosephosphate
      isomerase.
AB  - The importance of the fully conserved active site proline, Pro168, for the
      reaction mechanism of triosephosphate isomerase (TIM) has been investigated by
      studying the enzymatic and crystallographic properties of the P168A variant of
      trypanosomal TIM. In TIM, Pro168 follows the key catalytic residue Glu167,
      situated at the beginning of the flexible active site loop (loop 6). Turnover
      numbers of the P168A variant for its substrates are reduced approximately 50
      fold, whereas the Km values are approximately 2 times lower. The affinity of the
      P168A variant for the transition state analogue 2-phosphoglycolate (2PG) is
      reduced 5-fold. The crystal structures of unliganded and liganded (2PG) P168A
      show that the phosphate moiety of 2PG is bound similarly as in wild-type TIM,
      whereas the interactions of the carboxylic acid moiety with the side chain of the
      catalytic Glu167 differ. The unique properties of the proline side chain at
      position 168 are required to transmit ligand binding to the conformational change
      of Glu167: the side chain of Glu167 flips from the inactive swung-out to the
      active swung-in conformation on ligand binding in wild-type TIM, whereas in the
      mutant this conformational change does not occur. Further structural comparisons
      show that in the wild-type enzyme the concerted movement of loop 6 and loop 7
      from unliganded-open to liganded-closed appears to be facilitated by the
      interactions of the phosphate moiety with loop 7. Apparently, the rotation of 90
      degrees of the Gly211-Gly212 peptide plane of loop 7 plays a key role in this
      concerted movement.

PMID- 17176071
TI  - Redesigning the PheA domain of gramicidin synthetase leads to a new understanding
      of the enzyme's mechanism and selectivity.
AB  - The PheA domain of gramicidin synthetase A, a non-ribosomal peptide synthetase,
      selectively binds phenylalanine along with ATP and Mg2+ and catalyzes the
      formation of an aminoacyl adenylate. In this study, we have used a novel protein
      redesign algorithm, K*, to predict mutations in PheA that should exhibit improved
      binding for tyrosine. Interestingly, the introduction of two predicted mutations
      to PheA did not significantly improve KD, as measured by equilibrium fluorescence
      quenching. However, the mutations improved the specificity of the enzyme for
      tyrosine (as measured by kcat/KM), primarily driven by a 56-fold improvement in
      KM, although the improvement did not make tyrosine the preferred substrate over
      phenylalanine. Using stopped-flow fluorometry, we examined binding of different
      amino acid substrates to the wild-type and mutant enzymes in the pre-steady state
      in order to understand the improvement in KM. Through these investigations, it
      became evident that substrate binding to the wild-type enzyme is more complex
      than previously described. These experiments show that the wild-type enzyme binds
      phenylalanine in a kinetically selective manner; no other amino acids tested
      appeared to bind the enzyme in the early time frame examined (500 ms).
      Furthermore, experiments with PheA, phenylalanine, and ATP reveal a two-step
      binding process, suggesting that the PheA-ATP-phenylalanine complex may undergo a
      conformational change toward a catalytically relevant intermediate on the pathway
      to adenylation; experiments with PheA, phenylalanine, and other nucleotides
      exhibit only a one-step binding process. The improvement in KM for the mutant
      enzyme toward tyrosine, as predicted by K*, may indicate that redesigning the
      side-chain binding pocket allows the substrate backbone to adopt productive
      conformations for catalysis but that further improvements may be afforded by
      modeling an enzyme:ATP:substrate complex, which is capable of undergoing
      conformational change.

PMID- 17176072
TI  - P-Glycoprotein (P-gp) expressed in a confluent monolayer of hMDR1-MDCKII cells
      has more than one efflux pathway with cooperative binding sites.
AB  - The multidrug resistance transporter P-glycoprotein (P-gp) effluxes a wide range
      of substrates and can be affected by a wide range of inhibitors or modulators.
      Many studies have presented classifications for these binding interactions,
      within either the context of equilibrium binding or the Michaelis-Menten enzyme
      analysis of the ATPase activity of P-gp. Our approach is to study P-gp transport
      and its inhibition using a physiologically relevant confluent monolayer of hMDR1
      MDCKII cells. We measure the elementary rate constants for P-gp efflux of
      substrates and study inhibition using pairwise combinations with a different
      unlabeled substrate acting as the inhibitor. Our current kinetic model for P-gp
      has only a single binding site, because a previous study proved that the mass
      action kinetics of efflux of a single substrate were not sensitive to whether
      there are one or more substrate-binding and efflux sites. In this study, using
      this one-site model, we found that, with "high" concentrations of either a
      substrate or an inhibitor, the elementary rate constants fitted independently for
      each of the substrates alone quantitatively predicted the efflux curves, simply
      applying the assumption that binding at the "one site" was competitive. On the
      other hand, at "low" concentrations of both the substrate and inhibitor, we found
      no inhibition of the substrate efflux, despite the fact that both the substrate
      and inhibitor were being well-effluxed. This was not an effect of excess "empty"
      P-gp molecules, because the competitive efflux model takes site occupancy into
      account. Rather, it is quantitative evidence that the substrate and inhibitor are
      being effluxed by multiple pathways within P-gp. Remarkably, increasing the
      substrate concentration above the "low" concentration, caused the inhibition to
      become competitive; i.e., the inhibitor became effective. These data and their
      analysis show that the binding of these substrates must be cooperative, either
      positive or negative.

PMID- 17176073
TI  - Antibody recognition of a flexible epitope at the DNA binding site of the human
      papillomavirus transcriptional regulator E2.
AB  - We have obtained a monoclonal antibody (ED15) against the C-terminal DNA-binding
      domain of the high-risk human papillomavirus strain-16 E2 protein that strongly
      interferes with its DNA-binding activity. We here characterize the recognition
      mechanism of this antibody and find that the ED15-E2 interaction has a strong
      electrostatic component, which correlates with the high proportion of acidic
      residues found in the antibody combining site. Further circular dichroism
      experiments in the presence of phosphate show that, in addition to electrostatic
      screening of key potential interactions, ionic strength affects the conformation
      of the epitope. In addition, the interaction is strongly modulated by pH, which
      correlates with the local flexibility of the epitope rather than the presence of
      pH sensitive residues at the interface. Noticeably, this finding is well
      correlated with the strong entropic component of the interaction. Site directed
      mutagenesis indicates that the ED15 epitope involves at least part of the DNA
      binding helix of E2, explaining the mAb inhibitory activity. At physiological
      salt concentrations, the equilibrium dissociation constant of the E2-ED15
      interaction is 10(-7) M and the association rate is 10(4) M-1 s-1, at least 1
      order of magnitude slower than those generally reported in the most extensively
      described "nonflexible" antibody-protein interactions, indicating the presence of
      a slow conformational rearrangement on the antigen as the rate-limiting step. The
      crucial role of antigen flexibility in antibody-protein recognition is discussed.

PMID- 17176074
TI  - A phosphoproteomic analysis of the ErbB2 receptor tyrosine kinase signaling
      pathways.
AB  - Overexpression of the ErbB2 receptor tyrosine kinase is common in human cancers
      and is associated with an increased level of metastasis. To better understand the
      cellular signaling networks activated by ErbB2, a phosphoproteomic analysis of
      tyrosine-phosphorylated proteins was carried out in ErbB2-overexpressing breast
      and ovarian cancer cell lines. A total of 153 phosphorylation sites were assigned
      on 78 proteins. Treatment of cells with Herceptin, a monoclonal antibody that
      inhibits ErbB2 activity, significantly reduced the number of detectable protein
      phosphorylation sites, suggesting that many of these proteins participate in
      ErbB2-driven cell signaling. Of the 71 proteins that were differentially
      phosphorylated, only 13 were previously reported to directly associate with
      ErbB2. The differentially phosphorylated proteins included kinases,
      adaptor/docking proteins, proteins involved in cell proliferation and migration,
      and several uncharacterized RNA binding proteins. Selective depletion of some of
      these proteins, including RNA binding proteins SRRM2, SFRS1, SFRS9, and SFRS10,
      by siRNAs reduced the rate of migration of ErbB2-overexpressing ovarian cancer
      cells.

PMID- 17176075
TI  - Construction of modified ribosomes for incorporation of D-amino acids into
      proteins.
AB  - While numerous biologically active peptides contain D-amino acids, the
      elaboration of such species is not carried out by ribosomal synthesis. In fact,
      the bacterial ribosome discriminates strongly against the incorporation of D
      amino acids from D-aminoacyl-tRNAs. To permit the incorporation of D-amino acids
      into proteins using in vitro protein-synthesizing systems, a strategy has been
      developed to prepare modified ribosomes containing alterations within the
      peptidyltransferase center and helix 89 of 23S rRNA. S-30 preparations derived
      from colonies shown to contain ribosomes with altered 23S rRNAs were found to
      exhibit enhanced tolerance for D-amino acids and to permit the elaboration of
      proteins containing D-amino acids at predetermined sites. Five specific amino
      acids in Escherichia coli dihydrofolate reductase and Photinus pyralis luciferase
      were replaced with D-phenylalanine and D-methionine, and the specific activities
      of the resulting enzymes were determined.

PMID- 17176076
TI  - Mutation of Tn5 transposase beta-loop residues affects all steps of Tn5
      transposition: the role of conformational changes in Tn5 transposition.
AB  - X-ray cocrystal structures of Tn5 transposase (Tnp) bound to its 19 base pair
      (bp) recognition end sequence (ES) reveal contacts between a beta-loop (amino
      acids 240-260) and positions 3, 4, 5, and 6 of the ES. Here, we show that
      mutations of residues in this loop affect both in vivo and in vitro
      transposition. Most mutations are detrimental, whereas some mutations at position
      242 cause hyperactivity. More specifically, mutations to the beta-loop affect
      every individual step of transposition tested. Mutants performing in vivo and in
      vitro transposition less efficiently also form fewer synaptic complexes, whereas
      hyperactive Tnps form more synaptic complexes. Surprisingly, two hypoactive
      mutations, K244R and R253L, also affect the cleavage steps of transposition with
      a much more dramatic effect on the second double end break (DEB) complex
      formation step, indicating that the beta-loop likely plays an important roll in
      positioning the substrate DNA within the catalytic site. Finally, all mutants
      tested decrease efficiency of the final transposition step, strand transfer. A
      disparity in cleavage rate constants in vitro for mutants with changes to the
      proline at position 242 on transposons flanked by ESs differing in the
      orientation of the A-T base pair at position 4 allows us to postulate that P242
      contacts the position 4 nucleotide pair. On the basis of these data, we propose a
      sequential model for end cleavage in Tn5 transposition in which the uncleaved PEC
      is not symmetrical, and conformational changes are necessary between the first
      and second cleavage events and also for the final strand transfer step of
      transposition.

PMID- 17176077
TI  - Determinants of sequence-specific DNA methylation: target recognition and
      catalysis are coupled in M.HhaI.
AB  - Sequence specificity studies of the wild-type bacterial DNA cytosine C5
      methyltransferase HhaI were carried out with cognate (5'GCGC3') and noncognate
      DNA substrates containing single base pair changes at the first and the fourth
      position (underlined). Specificity for noncognate site methylation at the level
      of kcat/KDDNA is decreased 9000-80000-fold relative to the cognate site,
      manifested through changes in methylation, or a prior step, and changes in KDDNA.
      Analysis of a new high-resolution enzyme-DNA cocrystal structure provides a
      partial mechanistic understanding of this discrimination. To probe the
      significance of conformational transitions occurring prior to catalysis in
      determining specificity, we analyzed the double mutant (H127A/T132A). These amino
      acid substitutions disrupt the interface between the flexible loop (residues 80
      99), which interacts with the DNA minor groove, and the active site. The mutant's
      methylation of the cognate site is essentially unchanged, yet its methylation of
      noncognate sites is decreased up to 460-fold relative to the wild-type enzyme. We
      suggest that a significant contribution to M.HhaI's specificity involves the
      stabilization of reaction intermediates prior to methyl transfer, mediated by DNA
      minor groove-protein flexible loop interactions.

PMID- 17176078
TI  - Structural properties of prion protein protofibrils and fibrils: an experimental
      assessment of atomic models.
AB  - Decades after the prion protein was implicated in transmissible spongiform
      encephalopathies, the structure of its toxic isoform and its mechanism of
      toxicity remain unknown. By gathering available experimental data, albeit low
      resolution, a few pieces of the prion puzzle can be put in place. Currently,
      there are two fundamentally different models of a prion protofibril. One has its
      building blocks derived from a molecular dynamics simulation of the prion protein
      under amyloidogenic conditions, termed the spiral model. The other model was
      constructed by threading a portion of the prion sequence through a beta-helical
      structure from the Protein Data Bank. Here we compare and contrast these models
      with respect to all of the available experimental information, including electron
      micrographs, symmetries, secondary structure, oligomerization interfaces,
      enzymatic digestion, epitope exposure, and disaggregation profiles. Much of this
      information was not available when the two models were introduced. Overall, we
      find that the spiral model is consistent with all of the experimental results. In
      contrast, it is difficult to reconcile several of the experimental observables
      with the beta-helix model. While the experimental constraints are of low
      resolution, in bringing together the previously disconnected experiments, we have
      developed a clearer picture of prion aggregates. Both the improved
      characterization of prion aggregates and the existing atomic models can be used
      to devise further experiments to better elucidate the misfolding pathway and the
      structure of prion protofibrils.

PMID- 17176079
TI  - Functional reconstitution of rhodopsin into tubular lipid bilayers supported by
      nanoporous media.
AB  - We report on a novel reconstitution method for G-protein-coupled receptors
      (GPCRs) that yields detergent-free, single, tubular membranes in porous anodic
      aluminum oxide (AAO) filters at concentrations sufficient for structural studies
      by solid-state NMR. The tubular membranes line the inner surface of pores that
      traverse the filters, permitting easy removal of detergents during sample
      preparation as well as delivery of ligands for functional studies. Reconstitution
      of bovine rhodopsin into AAO filters did not interfere with rhodopsin function.
      Photoactivation of rhodopsin in AAO pores, monitored by UV-vis spectrophotometry,
      was indistinguishable from rhodopsin in unsupported unilamellar liposomes. The
      rhodopsin in AAO pores is G-protein binding competent as shown by a
      [35S]GTPgammaS binding assay. The lipid-rhodopsin interaction was investigated by
      2H NMR on sn-1- or sn-2-chain perdeuterated 1-stearoyl-2-docosahexaenoyl-sn
      glycero-3-phospholine as a matrix lipid. Rhodopsin incorporation increased mosaic
      spread of bilayer orientations and contributed to spectral density of motions
      with correlation times in the range of nano- to microseconds, detected as a
      significant reduction in spin-spin relaxation times. The change in lipid chain
      order parameters due to interaction with rhodopsin was insignificant.

PMID- 17176080
TI  - Solution structure and functional characterization of jingzhaotoxin-XI: a novel
      gating modifier of both potassium and sodium channels.
AB  - JZTX-XI is a peptide toxin isolated from the venom of the Chinese spider
      Chilobrachys jingzhao. It contains 34 residues including six cysteine residues
      with disulfide bridges linked in the pattern of I-IV, II-V, and III-VI. Using 3'-
      and 5'-RACE methods, the full-length cDNA was identified as encoding an 86
      residue precursor of JZTX-XI. In the electrophysiological assay, JZTX-XI shows
      activity toward the Kv2.1 channel in a way similar to hanatoxin1 and SGTx1 that
      both the activation and the deactivation processes are affected, which is in
      accordance with the high sequence homology among them (over 60% identity). On the
      other hand, JZTX-XI also exhibits specific interaction against the Nav channels
      of rat cardiac myocytes with a significant reduction in the peak current and
      slowing of channel inactivation. The solution structure of native JZTX-XI was
      determined by 1H NMR methods to identify the structural basis of these specific
      activities. Structural comparison of JZTX-XI with other gating modifier toxins
      shows that they all adopt a similar surface profile, a hydrophobic patch
      surrounded by charged residues such as Arg or Lys, which might be a common
      structural factor responsible for toxin-channel interaction. JZTX-XI might be an
      ideal tool to further investigate how spider toxins recognize various ion
      channels as their targets.

PMID- 17176081
TI  - Human opioid peptide Met-enkephalin binds to anionic phosphatidylserine in high
      preference to zwitterionic phosphatidylcholine: natural-abundance 13C NMR study
      on the binding state in large unilamellar vesicles.
AB  - A human opioid neuropeptide, Met-enkephalin (M-Enk: Tyr1-Gly2-Gly3-Phe4-Met5),
      having no net charge binds to anionic phosphatidylserine (PS) in high preference
      to zwitterionic phosphatidylcholine (PC). The binding mechanism in the PS and PC
      bilayers was studied on the basis of the inter- and intramolecular interaction
      data obtained by natural-abundance 13C nuclear magnetic resonance (NMR) of the
      peptide. Prominent upfield changes of the 13C resonance were observed in the C
      terminal residue upon binding to PS, whereas no such marked change was observed
      upon binding to PC. The upfield chemical shift changes with their characteristic
      carbon site dependence are ascribed to the electrostatic binding between the
      peptide C-terminal CO2- and the PS headgroup NH3+. Despite the net negative
      charge of the PS bilayer surface, M-Enk thus anchors the negatively charged C
      terminus. In the N-terminal residue, on the other hand, marked downfield chemical
      shift changes are observed upon binding to both the PS and PC bilayers, the
      magnitude of the changes being much larger in the PS system. The downfield
      changes with their characteristic carbon site dependence are ascribed to the
      electrostatic binding between the peptide N-terminal NH3+ and the lipid headgroup
      negative charge(s) (CO2- or PO4- in PS, PO4- in PC). Perturbation on the signal
      half-widths due to membrane binding also indicates the preferential and deeper
      binding of M-Enk on the PS membrane surface than on the PC membrane surface.
      Local charge cancellation takes place efficiently between M-Enk termini and the
      PS headgroups and compensates for the strong electrostatic hydration of the ionic
      groups. Distribution of the charged (positive and negative) and uncharged sites
      in the headgroups along the bilayer normal is responsible for the marked
      difference between PS and PC headgroups in controlling the binding state of the
      zwitterionic M-Enk.

PMID- 17176082
TI  - Alpha-synuclein adopts an alpha-helical conformation in the presence of
      polyunsaturated fatty acids to hinder micelle formation.
AB  - Alpha-synuclein is a small cytosolic protein involved in the pathogenesis of
      Parkinson's disease and other neurodegenerative disorders. Recent studies
      suggested a lipid-related function for this brain-enriched protein. Since the
      brain carries a high level of docosahexaenoic acid (DHA) and since the extent of
      alpha-synuclein gene expression increases in response to DHA intake, we have
      investigated the interaction of alpha-synuclein with this essential omega-3 fatty
      acid. We show that alpha-synuclein allows DHA to be present in a soluble rather
      than micellar form. Upon interaction with DHA, the normally unstructured alpha
      synuclein rapidly adopts an alpha-helical conformation. Prolonged exposure to
      DHA, however, gradually converts alpha-synuclein into amyloid-like fibrils. These
      results identify a potential biological function for alpha-synuclein and define
      an omega-3-linked pathway leading to alpha-synuclein aggregation.

PMID- 17176083
TI  - Rapid conformational dynamics of cytochrome P450 2E1 in a natural biological
      membrane environment.
AB  - Among the members of the cytochrome P450 superfamily, P450 2E1 is most often
      associated with the production of reactive oxygen species and subsequent cellular
      toxicity. We sought to identify a structural basis for this distinguishing
      feature of P450 2E1 by examining its carbon monoxide binding kinetics as a probe
      of conformation/dynamics. We employed liver microsomes from wild-type and P450
      2E1 knockout mice in order to characterize this P450 in a natural membrane
      environment. The CO binding kinetics of the P450s of wild-type microsomes had a
      rapid component that was absent in the knockout microsomes. Data analysis using
      the maximum entropy method (MEM) correspondingly identified two distinct kinetic
      components in the wild-type microsomes and only one component in the knockout
      microsomes. The rapid kinetic component in wild-type microsomes was attributed to
      endogenous P450 2E1, while the slower component was derived from the remaining
      P450s. In addition, rapid binding kinetics and a single component were also
      observed for human P450 2E1 in a baculovirus expression system, in the absence of
      other P450s. Binding kinetics of both mouse and human P450 2E1 were slowed in the
      presence of ethanol, a modulator of this P450. The unusually rapid CO binding
      kinetics of P450 2E1 indicate that it is more dynamically mobile than other P450s
      and thus able to more readily interconvert among alternate conformations. This
      suggests that conformational switching during the catalytic cycle may promote
      substrate release from a short-lived binding site, allowing activated oxygen to
      attack other targets with toxic consequences.

PMID- 17176084
TI  - The all-trans-15-syn-retinal chromophore of metarhodopsin III is a partial
      agonist and not an inverse agonist.
AB  - Meta III is formed during the decay of rhodopsin's active receptor state at
      neutral to alkaline pH by thermal isomerization of the retinal Schiff base C15=N
      bond, converting the ligand from all-trans 15-anti to all-trans 15-syn. The
      thereby induced change of ligand geometry switches the receptor to an inactive
      conformation, such that the decay pathway to Meta III contributes to the
      deactivation of the signaling state at higher pH values. We have examined the
      conformation of Meta III over a wider pH range and found that Meta III exists in
      a pH-dependent conformational equilibrium between this inactive conformation at
      neutral to alkaline pH and an active conformation similar to that of Meta II,
      which, however, is assumed at very acidic pH only. The apparent pKa of this
      transition is around 5.1 and thus several units lower than that of the Meta
      I/Meta II photoproduct equilibrium with its all-trans 15-anti ligand, but still
      about 1 unit higher than that of the opsin conformational equilibrium in the
      absence of ligand. The all-trans-15-syn-retinal chromophore is therefore not an
      inverse agonist like 11-cis- or 9-cis-retinal, which lock the receptor in an
      inactive conformation, but a classical partial agonist, which is capable of
      activating the receptor, yet with an efficiency considerably lower than the full
      agonist all-trans 15-anti. As the Meta III chromophore differs structurally from
      this full agonist only in the isomeric state of the C15=N bond, this ligand
      represents an excellent model system to study principal mechanisms of partial
      agonism which are helpful to understand the partial agonist behavior of other
      ligands.

PMID- 17176086
TI  - The marine natural product adociasulfate-2 as a tool to identify the MT-binding
      region of kinesins.
AB  - Kinesins are molecular motors that transport cargo along microtubules (MTs). To
      move forward the motor must attach to the MT in a defined orientation and detach
      from it in a process that is driven by ATP hydrolysis. The knowledge of the motor
      MT interface is essential for a detailed understanding of how kinesins move along
      MTs and how they are related to other molecular motors such as myosins or
      dyneins. We have used the marine natural product adociasulfate-2 (AS-2),
      previously identified as a MT-competitive inhibitor of conventional kinesin, to
      infer the secondary structure elements forming the MT interface of two human
      mitotic kinesins, namely, CENP-E and Eg5. AS-2 inhibits both basal and MT
      stimulated ATPase activities of CENP-E (IC50 of 8.6 and 1.3 microM, respectively)
      and Eg5 (IC50 of 3.5 and 5.3 microM, respectively) and is a MT-competitive
      inhibitor of CENP-E with a Ki of 0.35 microM. Binding of AS-2 to CENP-E also
      stimulates the ADP release from the nucleotide-binding pocket. AS-2 is a
      nonspecific kinesin inhibitor targeting several superfamily members including
      KHC, MPP1, MKLP1, RabK6, KIFC1, KIFC3, CENP-E, and Eg5. By measuring
      hydrogen/deuterium exchange with mass spectrometry we have shown that the
      formation of the CENP-E/AS-2 complex decreases the solvent accessibility of three
      neighboring peptides on the same face of CENP-E. We deduce that this is the site
      of MT attachment and conclude that loop L11, helix alpha4, loop L12, helix
      alpha5, loop L8, and strand beta5 constitute the main MT interface of the CENP-E
      motor domain. Similarly for Eg5/AS-2, a region of increased solvent accessibility
      locates the MT interface of Eg5.

PMID- 17176087
TI  - Site-selective modifications of arginine residues in human hemoglobin induced by
      methylglyoxal.
AB  - Methylglyoxal (MG) is an important glycating agent produced under physiological
      conditions. MG could react with DNA and proteins to generate advanced glycation
      end products. Human hemoglobin, the most abundant protein in blood cells, has not
      been systematically investigated as the target protein for methylglyoxal
      modification. Here we examined carefully, by using HPLC coupled with tandem mass
      spectrometry (LC-MS/MS), the covalent modifications of human hemoglobin induced
      by methylglyoxal. Our results revealed that hemoglobin could be modified by
      methylglyoxal, and the major form of modification was found to be the
      hydroimidazolone derivative of arginine residues. In addition, Arg-92 and Arg-141
      in the alpha chain as well as Arg-40 and Arg-104 in the beta chain were modified,
      whereas two other arginine residues, that is, Arg-31 in the alpha chain and Arg
      30 in the beta chain, were not modified. Semiquantitative measurement for adduct
      formation, together with the analysis of the X-ray structure of hemoglobin,
      showed that the extents of arginine modification were highly correlated with the
      solvent accessibilities of these residues. The facile formation of
      hydroimidazolone derivatives of arginine residues in hemoglobin by methylglyoxal
      at physiologically relevant concentrations suggested that this type of
      modification might occur in vivo. The unambiguous determination of the sites and
      extents of methylglyoxal modifications of arginines in hemoglobin provided a
      basis for understanding the implications of these modifications and for employing
      this type of hemoglobin modification as molecular biomarkers for clinical
      applications.

PMID- 17176085
TI  - Micelle-induced folding of spinach thylakoid soluble phosphoprotein of 9 kDa and
      its functional implications.
AB  - Thylakoid soluble phosphoprotein of 9 kDa (TSP9) has been identified as a plant
      specific protein in the photosynthetic thylakoid membrane (Carlberg et al. (2003)
      Proc. Natl. Acad. Sci. 100, 757-762). Nonphosphorylated TSP9 is associated with
      the membrane, whereas, after light-induced phosphorylation, a fraction of the
      phosphorylated TSP9 is released into the aqueous stroma. By NMR spectroscopy, we
      have determined the structural features of nonphosphorylated TSP9 both in aqueous
      solution and in membrane mimetic micelles. The results show that both wild type
      nonphosphorylated TSP9 and a triple-mutant (T46E + T53E + T60E) mimic of the
      triphosphorylated form of TSP9 are disordered under aqueous conditions, but adopt
      an ordered conformation in the presence of detergent micelles. The micelle
      induced structural features, which are similar in micelles either of SDS or
      dodecylphosphocholine (DPC), consist of an N-terminal alpha-helix, which may
      represent the primary site of interaction between TSP9 and binding partners, and
      a less structured helical turn near the C-terminus. These structured elements
      contain mainly hydrophobic residues. NMR relaxation data for nonphosphorylated
      TSP9 in SDS micelles indicated that the molecule is highly flexible with the
      highest order in the N-terminal alpha-helix. Intermolecular NOE signals, as well
      as spin probe-induced broadening of NMR signals, demonstrated that the SDS
      micelles contact both the structured and a portion of the unstructured regions of
      TSP9, in particular, those containing the three phosphorylation sites (T46, T53,
      and T60). This interaction may explain the selective dissociation of
      phosphorylated TSP9 from the membrane. Our study presents a structural model for
      the role played by the structured and unstructured regions of TSP9 in its
      membrane association and biological function.

PMID- 17176088
TI  - Glycine-rich transmembrane helix 10 in the staphylococcal tetracycline
      transporter TetA(K) lines a solvent-accessible channel.
AB  - The staphylococcal TetA(K) tetracycline exporter is classified within the major
      facilitator superfamily of transport proteins and contains 14 alpha-helical
      transmembrane segments (TMS). Using cysteine-scanning mutagenesis, 27 amino acid
      residues across and flanking putative TMS 10 of the TetA(K) transporter were
      individually replaced with cysteine. The level of solvent accessibility to each
      of the targeted amino acid positions was determined as a measure of fluorescein
      maleimide reactivity and demonstrated that TMS 10 of TetA(K) has a cytoplasmic
      boundary at G313 and is likely to extend from at least V298 on the periplasmic
      side. TMS 10 was found to be amphiphilic containing at least partially solvent
      accessible amino acid residues along the length of one helical face, suggesting
      that this helix may line a solvent-exposed channel. Functional analyses of these
      cysteine mutants demonstrated a significant role for a number of amino acid
      residues, including a predominance of glycine residues which were further
      analyzed by alanine substitution. These residues are postulated to allow
      interhelical interactions between TMS 10 and distal parts of TetA(K) that are
      likely to be required for the tetracycline transport mechanism in TetA(K) and may
      be a general feature required by bacterial tetracycline transporters for
      activity.

PMID- 17176090
TI  - Role of arginine-163 and the 163REEK166 motif in the oligomerization of truncated
      alpha A-crystallins.
AB  - To gain insight into the mechanism by which Arg-163 influences oligomerization of
      alphaA-crystallin, we prepared a series of truncated alphaA-crystallins with or
      without mutation of the Arg-163 residue. Expression of the proteins was achieved
      in Escherichia coli BL21 (DE3) pLysS cells, and alphaA-crystallin was purified by
      size-exclusion chromatography. Molecular mass was determined by molecular sieve
      HPLC, chaperone activity was assayed with alcohol dehydrogenase as the target
      protein, and structural changes were ascertained by circular dichroism (CD)
      measurements. With an increasing number of residues deleted, there was about a 3%
      decrease in oligomeric size per residue, until 10 residues were deleted. When 11
      residues, including Arg-163, were deleted, the oligomeric size decreased 85%.
      Mutation of Arg-163 to Gly (R163G) did not affect the molecular mass in the full
      length alphaA-crystallin. However, R163G mutants of all the truncated alphaA
      crystallins showed a decrease in oligomeric size, those lacking 8, 9, and 10
      residues showing 60-80% decrease and those lacking 5, 6, and 7 residues showing
      only a 7-14% decrease as compared to the corresponding truncated alphaA
      crystallin. These data suggest that R163, E164, E165, and K166 in the REEK motif
      are also relevant to alphaA-crystallin oligomerization. The molecular masses of
      alphaA1-163 and alphaA1-163 (R163K) were nearly the same, which suggests that the
      role of Arg-163 is to provide a positive charge for intersubunit electrostatic
      interactions in the C-terminal domain. In alphaA1-162 (S162R), recovery of the
      molecular mass to the level in alphaA1-163 has not occurred; this shows that the
      actual position of R163 is important.

PMID- 17176089
TI  - Cytoskeletal tension regulates both expression and degradation of h2-calponin in
      lung alveolar cells.
AB  - Calponin is an actin filament-associated regulatory protein, and its h2 isoform
      is expressed in lung alveolar epithelial cells under postnatal upregulation
      during lung development corresponding to the commencement of respiratory
      expansion. Consistent with this correlation to mechanical tension, the expression
      of h2-calponin in alveolar cells is dependent on substrate stiffness and
      cytoskeleton tension. The function of h2-calponin in the stability of actin
      cytoskeleton implicates a role in balancing the strength and compliance of
      alveoli. An interesting finding is a rapid degradation of h2-calponin in lung
      after prolonged deflation, which is prevented by inflation of the lung to the in
      situ expanded volume. Decreasing mechanical tension in cultured alveolar cells by
      reducing the dimension of culture matrix reproduced the degradation of h2
      calponin. Inhibition of myosin II ATPase also resulted in the degradation of h2
      calponin in alveolar cells, showing a determining role of the tension in the
      actin cytoskeleton. Alveolar cells statically cultured on silicon rubber membrane
      build high tension in the cytoskeleton corresponding to a high expression of h2
      calponin. Chronic cyclic stretching of cells on the membrane did not increase but
      decreased the expression of h2-calponin. This finding suggests that when cellular
      structure adapts to the stretched dimension, cyclic relaxations periodically
      release cytoskeleton tension and lower the total amount of tension that the cell
      senses over time. Therefore, the isometric tension, other than tension dynamics,
      determines the expression of h2-calponin. The tension regulation of h2-calponin
      synthesis and degradation demonstrates a novel mechanical regulation of cellular
      biochemistry.

PMID- 17176091
TI  - Characterization of two VQIXXK motifs for tau fibrillization in vitro.
AB  - Tau proteins are building blocks of the filaments that form neurofibrillary
      tangles of Alzheimer's disease (AD) and related neurodegenerative tauopathies. It
      was recently reported that two VQIXXK motifs in the microtubule (MT) binding
      region, named PHF6 and PHF6*, are responsible for tau fibrillization. However,
      the exact role each of these motifs plays in this process has not been analyzed
      in detail. Using a recombinant human tau fragment containing only the four MT
      binding repeats (K18), we show that deletion of either PHF6 or PHF6* affected tau
      assembly but only PHF6 is essential for filament formation, suggesting a critical
      role of this motif. To determine the amino acid residues within PHF6 that are
      required for tau fibrillization, a series of deletion and mutation constructs
      targeting this motif were generated. Deletion of VQI in either PHF6 or PHF6*
      lessened but did not eliminate K18 fibrillization. However, removal of the single
      K311 residue from PHF6 completely abrogated the fibril formation of K18. K311D
      mutation of K18 inhibited tau filament formation, while K311A and K311R mutations
      had no effect. These data imply that charge change at position 311 is important
      in tau fibril formation. A similar requirement of nonnegative charge at this
      position for fibrillization was observed with the full-length human tau isoform
      (T40), and data from these studies indicate that the formation of fibrils by
      T40K311D and T40K311P mutants is repressed at the nucleation phase. These
      findings provide important insights into the mechanisms of tau fibrillization and
      suggest targets for AD drug discovery to ameliorate neurodegeneration mediated by
      filamentous tau pathologies.

PMID- 17176092
TI  - Kinetics of inhibition of beta-amyloid aggregation by transthyretin.
AB  - Deposition of beta-amyloid (Abeta) fibrils is an early event in the
      neurodegenerative processes associated with Alzheimer's disease. According to the
      "amyloid cascade" hypothesis, Abeta aggregation, and its subsequent deposition as
      fibrils, is the underlying cause of disease. Abeta is a proteolytic product of
      amyloid precursor protein (APP); several mutations in APP have been identified
      that are associated with early onset of disease. Transgenic mice overexpressing
      APP with the Swedish mutation develop numerous plaques but, surprisingly, lack
      the neurofibrillary tangles and neuronal loss characteristic of Alzheimer's
      disease, in apparent contradiction of the amyloid cascade hypothesis. However,
      recent studies suggest that coproduction of sAPPalpha, an alternative proteolytic
      product of APP, increases synthesis of transthyretin that, in turn, interacts
      directly with Abeta to inhibit its toxicity. Here we report results from
      biophysical analysis of Abeta aggregation kinetics in the presence of
      transthryetin. At substoichiometric ratios, transthyretin drastically decreased
      the rate of aggregation without affecting the fraction of Abeta in the aggregate
      pool. Detailed analysis of the data using a mathematical model demonstrated that
      the decrease in aggregation rate was due to both a decrease in the rate of
      elongation relative to the rate of initiation of filaments and a decrease in
      lateral association of filaments to fibrils. Tryptophan quenching data indicated
      that transthyretin binds weakly to Abeta, with an estimated apparent KS of 2300 M
      1. Taken together, the data support a hypothesis wherein transthyretin
      preferentially binds to aggregated rather than monomeric Abeta and arrests
      further growth of the aggregates.

PMID- 17176093
TI  - Isolation and characterization of a proteinase K-sensitive PrPSc fraction.
AB  - Recent studies have shown that a sizable fraction of PrPSc present in prion
      infected tissues is, contrary to previous conceptions, sensitive to digestion by
      proteinase K (PK). This finding has important implications in the context of
      diagnosis of prion disease, as PK has been extensively used in attempts to
      distinguish between PrPSc and PrPC. Even more importantly, PK-sensitive PrPSc
      (sPrPSc) might be essential to understand the process of conversion and
      aggregation of PrPC leading to infectivity. We have isolated a fraction of
      sPrPSc. This material was obtained by differential centrifugation at an
      intermediate speed of Syrian hamster PrPSc obtained through a conventional
      procedure based on ultracentrifugation in the presence of detergents. PK
      sensitive PrPSc is completely degraded under standard conditions (50 mug/mL of
      proteinase K at 37 degrees C for 1 h) and can also be digested with trypsin.
      Centrifugation in a sucrose gradient showed sPrPSc to correspond to the lower
      molecular weight fractions of the continuous range of oligomers that constitute
      PrPSc. PK-sensitive PrPSc has the ability to convert PrPC into protease-resistant
      PrPSc, as assessed by the protein misfolding cyclic amplification assay (PMCA).
      Limited proteolysis of sPrPSc using trypsin allows for identification of regions
      that are particularly susceptible to digestion, i.e., are partially exposed and
      flexible; we have identified as such the regions around residues K110, R136,
      R151, K220, and R229. PK-sensitive PrPSc isolates should prove useful for
      structural studies to help understand fundamental issues of the molecular biology
      of PrPSc and in the quest to design tests to detect preclinical prion disease.

PMID- 17176094
TI  - Roles of salt and conformation in the biological and physicochemical behavior of
      protegrin-1 and designed analogues: correlation of antimicrobial, hemolytic, and
      lipid bilayer-perturbing activities.
AB  - Protegrins are short (16-18 residues) cationic peptides from porcine leukocytes
      that display potent, broad-spectrum antimicrobial activity. Protegrin-1 (PG-1),
      one of five natural homologues, adopts a rigid beta-hairpin structure that is
      stabilized by two disulfide bonds. We have previously employed the principles of
      beta-hairpin design to develop PG-1 variants that lack disulfide bonds but
      nevertheless display potent antimicrobial activity [Lai, J. R., Huck, B. R.,
      Weisblum, B., and Gellman, S. H. (2002) Biochemistry 41, 12835-12842.]. The
      activity of these disulfide-free variants, however, is attenuated in the presence
      of salt, and the activity of PG-1 itself is not. Salt-induced inactivation of
      host-defense peptides, such as human defensins, is thought to be important in
      some pathological situations (e.g., cystic fibrosis), and the variation in salt
      sensitivity among our PG-1 analogues offers a model system with which to explore
      the origins of these salt effects. We find that the variations in antimicrobial
      activity among our peptides are correlated with the folding propensities of these
      molecules and with the extent to which the peptides induce leakage of contents
      from synthetic liposomes. Comparable correlations were observed between folding
      and hemolytic activity. The extent to which added salt reduces antimicrobial
      activity parallels salt effects on vesicle perturbation, which suggests that the
      biological effects of high salt concentrations arise from modulation of peptide
      membrane interactions.

PMID- 17176096
TI  - Interaction of heparin with two synthetic peptides that neutralize the
      anticoagulant activity of heparin.
AB  - Two synthetic analogues of the heparin-binding domain of heparin/heparan sulfate
      interacting protein (Ac-SRGKAKVKAKVKDQTK-NH2) and the all-d-amino acid version of
      the same peptide (l-HIPAP and d-HIPAP, respectively) were synthesized, and their
      efficacy as agents for neutralization of the anticoagulant activity of heparin
      was assayed. The two analogue peptides were found to be equally effective for
      neutralization of the anticoagulant activity of heparin, as measured by
      restoration of the activity of serine protease factor Xa by the Coatest heparin
      method. The finding that l-HIPAP and d-HIPAP are equally effective suggests that
      d-amino acid peptides show promise as proteolytically stable therapeutic agents
      for neutralization of the anticoagulant activity of heparin. The interaction of l
      HIPAP and d-HIPAP with heparin was characterized by 1H NMR, isothermal titration
      calorimetry (ITC), and heparin affinity chromatography. The two peptides were
      found to interact identically with heparin. Analysis of the dependence of heparin
      peptide binding constants on Na+ concentration by counterion condensation theory
      indicates that, on average, 2.35 Na+ ions are displaced from heparin per peptide
      molecule bound and one peptide molecule binds per hexasaccharide segment of
      heparin. The analysis also indicates that both ionic and nonionic interactions
      contribute to the binding constant, with the ionic contribution decreasing as the
      Na+ concentration increases.

PMID- 17176095
TI  - Lipid-binding activity of intrinsically unstructured cytoplasmic domains of
      multichain immune recognition receptor signaling subunits.
AB  - Multichain immune recognition receptors (MIRRs) found on the surface of T cells,
      B cells, mast cells, natural killer cells, basophils, and other immune cells are
      formed by the association of several single-pass transmembrane proteins, with
      immunoglobulin-like ligand recognition domains and signal-transducing domains
      present on separate subunits. The MIRR signaling subunits all have cytoplasmic
      domains containing one or more copies of an immunoreceptor tyrosine-based
      activation motif (ITAM), tyrosine residues of which are phosphorylated upon
      receptor engagement in an early and obligatory event in the signaling cascade.
      Despite the proximity to the cell membrane and crucial role in transmembrane
      signal transduction, little is known about the structure and lipid-binding
      activity of the ITAM-containing cytoplasmic domains. Here we investigate the
      conformation and lipid-binding activity of several MIRR cytoplasmic domains,
      namely, T cell receptor zetacyt, CD3epsiloncyt, CD3deltacyt, and CD3gammacyt, B
      cell receptor Igalphacyt and Igbetacyt, and Fc receptor FcepsilonRIgammacyt,
      using purified recombinant proteins. Secondary structure prediction analysis and
      experimental circular dichroism spectra identify each of these cytoplasmic
      domains as natively unfolded proteins. We also report that zetacyt,
      CD3epsiloncyt, and FcepsilonRIgammacyt bind to acidic and mixed phospholipid
      vesicles and that the binding strength correlates with the protein net charge and
      the presence of clustered basic amino acid residues. Circular dichroism analysis
      reveals the lack of secondary structure for these domains in lipid-bound form.
      Phosphorylation of zetacyt and FcepsilonRIgammacyt does not alter their random
      coil conformation but weakens binding to membranes. The implications of these
      results for transmembrane signal transduction by immune receptors are discussed.

PMID- 17176097
TI  - An optical signal correlated with the allosteric transition in Scapharca
      inaequivalvis HbI.
AB  - The transient absorbance change within the first 2 mus of photolysis of COHbI
      (from Scapharca inaequivalvis) reported by Chiancone et al. [Chiancone, E.,
      Elber, R., Royer, W. E., Regan, R., and Gibson, Q. H. (1993) J. Biol. Chem. 268,
      5711-5718] has been studied in several mutants. Evidence is presented that this
      change (rts) is associated with the allosteric transition between R and T states.
      Two different rts spectra relate to Hb2 and Hb2CO. No rts has been observed for
      mutants at position 97 (normally Phe). Correlation of ligand binding and rts
      shows that protein function changes at or near the rates of rts, typically, 2 x
      10(6) s-1 (Hb2) and 5 x 10(5) s-1 (Hb2CO). Unique values of allosteric parameters
      for several mutants have been obtained by combining kinetic and equilibrium data.
      The effect of mutation on function thus may be assigned to allostery or to a
      change in intrinsic heme reactivity.

PMID- 17176099
TI  - Effect of cholesterol on the interaction of the HIV GP41 fusion peptide with
      model membranes. Importance of the membrane dipole potential.
AB  - Fusion of viral and cell membranes is a key event in the process by which the
      human immunodeficiency virus (HIV) enters the target cell. Membrane fusion is
      facilitated by the interaction of the viral gp41 fusion peptide with the cell
      membrane. Using synthetic peptides and model membrane systems, it has been
      established that the sequence of events implies the binding of the peptide to the
      membrane, followed by a conformational change (transformation of unordered and
      helical structures into beta-aggregates) which precedes lipid mixing. It is known
      that this process can be influenced by the membrane lipid composition. In the
      present work we have undertaken a systematic study in order to determine the
      influence of cholesterol (abundant in the viral membrane) in the sequence of
      events leading to lipid mixing. Besides its effect on membrane fluidity,
      cholesterol can affect a less known physical parameter, the membrane dipole
      potential. Using the dipole potential fluorescent sensor di-8-ANEPPS together
      with other biophysical techniques, we show that cholesterol increases the
      affinity of the fusion peptide for the model membranes, and although it lowers
      the extent of lipid mixing, it increases the mixing rate. The influence of
      cholesterol on the peptide affinity and the lipid mixing rate are shown to be
      mainly due to its influence of the membrane dipole potential, whereas the lipid
      mixing extent and peptide conformational changes seem to be more dependent on
      other membrane parameters such as membrane fluidity and hydration.

PMID- 17176100
TI  - Comparative analysis of calcineurin inhibition by complexes of immunosuppressive
      drugs with human FK506 binding proteins.
AB  - Multiple intracellular receptors of the FK506 binding protein (FKBP) family of
      peptidylprolyl cis/trans-isomerases are potential targets for the
      immunosuppressive drug FK506. Inhibition of the protein phosphatase calcineurin
      (CaN), which has been implicated in the FK506-mediated blockade of T cell
      proliferation, was shown to involve a gain of function in the FKBP12/FK506
      complex. We studied the potential of six human FKBPs to contribute to CaN
      inhibition by comparative examination of inhibition constants of the respective
      FK506/FKBP complexes. Interestingly, these FKBPs form tight complexes with FK506,
      exhibiting comparable dissociation constants, but the resulting FK506/FKBP
      complexes differ greatly in their affinity for CaN, with IC50 values in the range
      of 0.047-17 microM. The different capacities of FK506/FKBP complexes to affect
      CaN activity are partially caused by substitutions corresponding to the amino
      acid side chains K34 and I90 of FKBP12. Only the FK506 complexes of FKBP12,
      FKBP12.6, and FKBP51 showed high affinity to CaN; small interfering RNA against
      these FKBP allowed defining the contribution of individual FKBP in an NFAT
      reporter gene assay. Our results allow quantitative correlation between FK506
      mediated CaN effects and the abundance of the different FKBPs in the cell.

PMID- 17176101
TI  - Glutamates 99 and 107 in transmembrane helix III of subunit I of cytochrome bd
      are critical for binding of the heme b595-d binuclear center and enzyme activity.
AB  - Cytochrome bd is a quinol oxidase of Escherichia coli under microaerophilic
      growth conditions. Coupling of the release of protons to the periplasm by quinol
      oxidation to the uptake of protons from the cytoplasm for dioxygen reduction
      generates a proton motive force. On the basis of sequence analysis, glutamates 99
      and 107 conserved in transmembrane helix III of subunit I have been proposed to
      convey protons from the cytoplasm to heme d at the periplasmic side. To probe a
      putative proton channel present in subunit I of E. coli cytochrome bd, we
      substituted a total of 10 hydrophilic residues and two glycines conserved in
      helices I and III-V and examined effects of amino acid substitutions on the
      oxidase activity and bound hemes. We found that Ala or Leu mutants of Arg9 and
      Thr15 in helix I, Gly93 and Gly100 in helix III, and Ser190 and Thr194 in helix V
      exhibited the wild-type phenotypes, while Ala and Gln mutants of His126 in helix
      IV retained all hemes but partially lost the activity. In contrast, substitutions
      of Thr26 in helix I, Glu99 and Glu107 in helix III, Ser140 in helix IV, and
      Thr187 in helix V resulted in the concomitant loss of bound heme b558 (T187L) or
      b595-d (T26L, E99L/A/D, E107L/A/D, and S140A) and the activity. Glu99 and Glu107
      mutants except E107L completely lost the heme b595-d center, as reported for heme
      b595 ligand (His19) mutants. On the basis of this study and previous studies, we
      propose arrangement of transmembrane helices in subunit I, which may explain
      possible roles of conserved hydrophilic residues within the membrane.

PMID- 17176098
TI  - Pyridoxamine analogues scavenge lipid-derived gamma-ketoaldehydes and protect
      against H2O2-mediated cytotoxicity.
AB  - Isoketals and levuglandins are highly reactive gamma-ketoaldehydes formed by
      oxygenation of arachidonic acid in settings of oxidative injury and
      cyclooxygenase activation, respectively. These compounds rapidly adduct to
      proteins via lysyl residues, which can alter protein structure/function. We
      examined whether pyridoxamine, which has been shown to scavenge alpha
      ketoaldehydes formed by carbohydrate or lipid peroxidation, could also
      effectively protect proteins from the more reactive gamma-ketoaldehydes.
      Pyridoxamine prevented adduction of ovalbumin and also prevented inhibition of
      RNase A and glutathione reductase activity by the synthetic gamma-ketoaldehyde,
      15-E2-isoketal. We identified the major products of the reaction of pyridoxamine
      with the 15-E2-isoketal, including a stable lactam adduct. Two lipophilic
      analogues of pyridoxamine, salicylamine and 5'-O-pentylpyridoxamine, also formed
      lactam adducts when reacted with 15-E2-isoketal. When we oxidized arachidonic
      acid in the presence of pyridoxamine or its analogues, pyridoxamine-isoketal
      adducts were found in significantly greater abundance than the pyridoxamine-N
      acyl adducts formed by alpha-ketoaldehyde scavenging. Therefore, pyridoxamine and
      its analogues appear to preferentially scavenge gamma-ketoaldehydes. Both
      pyridoxamine and its lipophilic analogues inhibited the formation of lysyl
      levuglandin adducts in platelets activated ex vivo with arachidonic acid. The two
      lipophilic pyridoxamine analogues provided significant protection against H2O2
      mediated cytotoxicity in HepG2 cells. These results demonstrate the utility of
      pyridoxamine and lipophilic pyridoxamine analogues to assess the potential
      contributions of isoketals and levuglandins in oxidant injury and inflammation
      and suggest their potential utility as pharmaceutical agents in these conditions.

PMID- 17176102
TI  - Mechanism of O2 activation by cytochrome P450cam studied by isotope effects and
      transient state kinetics.
AB  - The early steps in dioxygen activation by the monooxygenase cytochrome P450cam
      (CYP101) include binding of O2 to ferrous P450cam to yield the ferric-superoxo
      form (oxyP450cam) followed by an irreversible, long-range electron transfer from
      putidaredoxin to reduce the oxyP450cam. The steady state kinetic parameter
      kcat/Km(O2) has been studied by a variety of probes that indicate a small D2O
      solvent isotope effect (1.21 +/- 0.08), a very small solvent viscosogen effect,
      and a 16O/18O isotope effect of 1.0147 +/- 0.0007. This latter value, which can
      be compared with the 16O/18O equilibrium isotope effect of 1.0048 +/- 0.0003
      measured for oxyP450cam formation, is attributed to a primarily rate-limiting
      outer-sphere electron transfer from the heme iron center as O2 that has prebound
      to protein approaches the active site cofactor. The electron transfer from
      putidaredoxin to oxyP450cam was investigated by rapid mixing at 25 degrees C to
      complement previous lower-temperature measurements. A rate of 390 +/- 23 s-1 (and
      a near-unity solvent isotope effect) supports the view that the long-range
      electron transfer from reduced putidaredoxin to oxyP450cam is rapid relative to
      dissociation of O2 from the enzyme. P450cam represents the first enzymatic
      reaction of O2 in which both equilibrium and kinetic 16O/18O isotope effects have
      been measured.

PMID- 17176103
TI  - Heteromeric complex formation between CYP2E1 and CYP1A2: evidence for the
      involvement of electrostatic interactions.
AB  - Mixed reconstituted systems containing CYP2B4, CYP1A2, and NADPH-cytochrome P450
      reductase were previously shown to exhibit a dramatic inhibition of 7
      pentoxyresorufin O-dealkylation (PROD) when compared to simple reconstituted
      systems containing reductase and a single P450 enzyme, results consistent with
      the formation of CYP1A2-CYP2B4 complexes where the reductase binds with high
      affinity to the CYP1A2 moiety of the complex. In this report, we provide evidence
      for an interaction between CYP1A2 and CYP2E1. Synergism of 7-ethoxyresorufin O
      deethylation (EROD) and PROD was observed when these P450s were combined in mixed
      reconstituted systems at subsaturating reductase concentrations. Higher ionic
      strength attenuated the synergistic stimulation of both PROD and EROD in mixed
      reconstituted systems, consistent with disruption of heteromeric CYP2E1-CYP1A2
      complexes. The effect of ionic strength was further examined as a function of
      reductase concentration. At lower ionic strength, there was a significant
      synergistic stimulation of EROD. This synergistic stimulation diminished with
      increasing reductase concentration, resulting in an additive response as
      reductase became saturating. Interestingly, at high ionic strength, the synergism
      of EROD in the mixed reconstituted system was not observed. In contrast, mixed
      reconstituted systems containing CYP2E1 and CYP2B4 did not provide evidence for
      the formation of these heteromeric P450-P450 complexes. The synergistic
      stimulation observed with the reductase-CYP1A2-CYP2E1 mixed reconstituted system
      is consistent with the formation of a CYP1A2-CYP2E1 complex. Taken together with
      the lack of a kinetically detectable interaction between CYP2B4 and CYP2E1, and
      the previously reported CYP1A2-CYP2B4 interaction, these results suggest that
      CYP1A2 may facilitate the formation of complexes with other P450 enzymes.

PMID- 17176105
TI  - Interaction of glutathione reductase with heavy metal: the binding of Hg(II) or
      Cd(II) to the reduced enzyme affects both the redox dithiol pair and the flavin.
AB  - To determine the inhibition mechanism of yeast glutathione reductase (GR) by
      heavy metal, we have compared the electronic absorption and resonance Raman (RR)
      spectra of the enzyme in its oxidized (Eox) and two-electron reduced (EH2) forms,
      in the absence and the presence of Hg(II) or Cd(II). The spectral data clearly
      show a redox dependence of the metal binding. The metal ions do not affect the
      absorption and RR spectra of Eox. On the contrary, the EH2 spectra, generated by
      addition of NADPH, are strongly modified by the presence of heavy metal. The
      absorption changes of EH2 are metal-dependent. On the one hand, the main flavin
      band observed at 450 nm for EH2 is red-shifted at 455 nm for the EH2-Hg(II)
      complex and at 451 nm for the EH2-Cd(II) complex. On the other hand, the
      characteristic charge-transfer (CT) band at 540 nm is quenched upon metal binding
      to EH2. In NADPH excess, a new CT band is observed at 610 nm for the EH2-Hg(II)
      NADPH complex and at 590 nm for EH2-Cd(II)-NADPH. The RR spectra of the EH2-metal
      complexes are not sensitive to the NADPH concentration. With reference to the RR
      spectra of EH2 in which the frequencies of bands II and III were observed at 1582
      and 1547 cm-1, respectively, those of the EH2-metal complexes are detected at
      1577 and 1542 cm-1, indicating an increased flavin bending upon metal
      coordination to EH2. From the frequency shifts of band III, a concomitant
      weakening of the H-bonding state of the N5 atom is also deduced. Taking into
      account the different chemical properties of Hg(II) and Cd(II), the coordination
      number of the bound metal ion was deduced to be different in GR. A mechanism of
      the GR inhibition is proposed. It proceeds primarily by a specific binding of the
      metal to the redox thiol/thiolate pair and the catalytic histidine of EH2. The
      bound metal ion then acts on the bending of the isoalloxazine ring of FAD as well
      as on the hydrophobicity of its microenvironment.

PMID- 17176104
TI  - Sequencing of oligoarabinosyl units released from mycobacterial arabinogalactan
      by endogenous arabinanase: identification of distinctive and novel structural
      motifs.
AB  - The mycobacterial D-arabinofuran is a common constituent of both cell wall
      mycolyl-arabinogalactan (AG) and the associated lipoarabinomannan (LAM), and is
      thus accorded critical structural and immunological roles. Despite a well
      recognized importance, progress in understanding its full structural
      characteristics beyond the nonreducing terminal motifs has hitherto been limited
      by available analytical tools. An endogenous arabinanase activity recently
      isolated from Mycobacterium smegmatis was previously shown to be capable of
      releasing large oligoarabinosyl units from AG. Advanced tandem mass spectrometry
      utilizing both low and high energy collision induced dissociation now afforded a
      facile way to map and directly sequence the digestion products which were
      dominated by distinctive Ara18 and Ara19 structural units, together with Ara7 and
      lesser amount of Ara11 and Ara12. Significantly, evidence was obtained for the
      first time which validated the linkages and branching pattern of the previously
      inferred Ara22 structural motif of AG, on which the preferred cleavage sites of
      the novel arabinanase could be localized. The established linkage-specific MS/MS
      fragmentation characteristics further led to identification of a galactosamine
      substituent on the C2 position of a portion of the internal 3,5-branched Ara
      residue of the AG of Mycobacterium tuberculosis, but not that of the
      nonpathogenic, fast growing M. smegmatis.

PMID- 17176106
TI  - Thermodynamics and kinetics of the glyoxylate cycle.
AB  - Because the standard Gibbs energies of formation of all the species of reactants
      in the glyoxylate cycle are known at 298.15 K, it is possible to calculate the
      apparent equilibrium constants of the five reactions in the cycle in the pH range
      5-9 and ionic strengths from 0 to approximately 0.35 M. In making calculations on
      such a system, it is convenient to specify concentrations of coenzymes like NADox
      and NADred because they are involved in many reactions and may be in steady
      states. Calculations are given for [NADox] = 1000[NADred] and [NADox] =
      10[NADred]. Equilibrium compositions are calculated using computer programs when
      all the reactants are present initially and when only glyoxylate and CoA are
      present initially. The kinetics of the reactions in the glyoxylate cycle at
      specified concentrations of NADox and NADred are calculated by numerical solution
      of the steady-state rate equations for the case where the reactant concentrations
      are below their Michaelis constants and only glyoxylate and CoA are present
      initially.

PMID- 17176108
TI  - Kinetic mechanism of glutaryl-CoA dehydrogenase.
AB  - Glutaryl-CoA dehydrogenase (GCD) is a homotetrameric enzyme containing one
      noncovalently bound FAD per monomer that oxidatively decarboxylates glutaryl-CoA
      to crotonyl-CoA and CO2. GCD belongs to the family of acyl-CoA dehydrogenases
      that are evolutionarily conserved in their sequence, structure, and function.
      However, there are differences in the kinetic mechanisms among the different acyl
      CoA dehydrogenases. One of the unanswered aspects is that of the rate-determining
      step in the steady-state turnover of GCD. In the present investigation, the major
      rate-determining step is identified to be the release of crotonyl-CoA product
      because the chemical steps and reoxidation of reduced FAD are much faster than
      the turnover of the wild-type GCD. Other steps are only partially rate
      determining. This conclusion is based on the transit times of the individual
      reactions occurring in the active site of GCD.

PMID- 17176107
TI  - Mechanistic studies of the flavoenzyme tryptophan 2-monooxygenase: deuterium and
      15N kinetic isotope effects on alanine oxidation by an L-amino acid oxidase.
AB  - Tryptophan 2-monooxygenase (TMO) from Pseudomonas savastanoi catalyzes the
      oxidative decarboxylation of l-tryptophan during the biosynthesis of indoleacetic
      acid. Structurally and mechanistically, the enzyme is a member of the family of l
      amino acid oxidases. Deuterium and 15N kinetic isotope effects were used to probe
      the chemical mechanism of l-alanine oxidation by TMO. The primary deuterium
      kinetic isotope effect was pH independent over the pH range 6.5-10, with an
      average value of 6.0 +/- 0.5, consistent with this being the intrinsic value. The
      deuterium isotope effect on the rate constant for flavin reduction by alanine was
      6.3 +/- 0.9; no intermediate flavin species were observed during flavin
      reduction. The kcat/Kala value was 1.0145 +/- 0.0007 at pH 8. NMR analyses gave
      an equilibrium 15N isotope effect for deprotonation of the alanine amino group of
      1.0233 +/- 0.0004, allowing calculation of the 15N isotope effect on the CH bond
      cleavage step of 0.9917 +/- 0.0006. The results are consistent with TMO oxidation
      of alanine occurring through a hydride transfer mechanism.

PMID- 17176110
TI  - Reactivity of penicillin-binding proteins with peptidoglycan-mimetic beta
      lactams: what's wrong with these enzymes?
AB  - Beta-lactams exert their antibiotic action through their inhibition of bacterial
      DD-peptidases (penicillin-binding proteins). Bacteria, in general, carry several
      such enzymes localized on the outside of their cell membrane to catalyze the
      final step in cell wall (peptidoglycan) synthesis. They have been classified into
      two major groups, one of high molecular weight, the other of low. Members of the
      former group act as transpeptidases in vivo, and their inhibition by beta-lactams
      leads to cessation of bacterial growth. The latter group consists of DD
      carboxypeptidases, and their inhibition by beta-lactams is generally not fatal to
      bacteria. We have previously shown that representatives of the former group are
      ineffective at catalyzing the hydrolysis/aminolysis of peptidoglycan-mimetic
      peptides in vitro [Anderson et al. (2003) Biochem. J. 373, 949-955]. The theme of
      these experiments is expanded in the present paper where we describe the
      synthesis of a series of beta-lactams (penicillins and cephalosporins) containing
      peptidoglycan-mimetic side chains and the kinetics of their inhibition of a panel
      of penicillin-binding proteins spanning the major classes (Escherichia coli PBP 2
      and PBP 5, Streptococcus pneumoniae PBP 1b, PBP 2x and PBP 3, the Actinomadura
      R39 DD-peptidase, and the Streptomyces R61 DD-peptidase). The results of these
      experiments mirror and expand the previous results with peptides. Neither
      peptides nor beta-lactams with appropriate peptidoglycan-mimetic side chains
      react with the solubilized constructs of membrane-bound penicillin binding
      proteins (the first five enzymes above) at rates exceeding those of generic
      analogues. Such peptides and beta-lactams do react at greatly enhanced rates with
      certain soluble low molecular weight enzymes (R61 and R39 DD-peptidases). The
      former result is unexpected and interesting. Why do the majority of penicillin
      binding proteins not recognize elements of local peptidoglycan structure?
      Possible answers are discussed. That this question needs to be asked casts
      fascinating shadows on current studies of penicillin-binding proteins for new
      drug design.

PMID- 17176109
TI  - Hydrophilic anilinogeranyl diphosphate prenyl analogues are Ras function
      inhibitors.
AB  - Sequential processing of H-Ras by protein farnesyl transferase (FTase), Ras
      converting enzyme (Rce1), and protein-S-isoprenylcysteine O-methyltransferase
      (Icmt) to give H-Ras C-terminal farnesyl-S-cysteine methyl ester is required for
      appropriate H-Ras membrane localization and function, including activation of the
      mitogen-activated protein kinase (MAPK) cascade. We employed a Xenopus laevis
      oocyte whole-cell model system to examine whether anilinogeranyl diphosphate
      analogues of similar shape and size, but with a hydrophobicity different from
      that of the FTase substrate farnesyl diphosphate (FPP), could ablate biological
      function of H-Ras. Analysis of oocyte maturation kinetics following
      microinjection of in vitro analogue-modified H-Ras into isoprenoid-depleted
      oocytes revealed that analogues with a hydrophobicity near that of FPP supported
      H-Ras biological function, while the analogues p-nitroanilinogeranyl diphosphate
      (p-NO2-AGPP), p-cyanoanilinogeranyl diphosphate (p-CN-AGPP), and
      isoxazolaminogeranyl diphosphate (Isox-GPP) with hydrophobicities 2-5 orders of
      magnitude lower than that of FPP did not. We found that although H-Ras modified
      with FPP analogues p-NO2-AGPP, p-CN-AGPP, and Isox-GPP was an efficient substrate
      for C-terminal postprenylation processing by Rce1 and Icmt, co-injection of H-Ras
      with analogues p-NO2-AGPP, p-CN-AGPP, or Isox-GPP could not activate MAPK. We
      propose that H-Ras biological function requires a minimum lipophilicity of the
      prenyl group to allow important interactions downstream of the C-terminal
      processed H-Ras protein. The hydrophilic FPP analogues p-NO2-AGPP, p-CN-AGPP, and
      Isox-GPP are H-Ras function inhibitors (RFIs) and serve as lead compounds for a
      unique class of potential anticancer therapeutics.

PMID- 17176111
TI  - Oxygenation of monounsaturated fatty acids by soybean lipoxygenase-1: evidence
      for transient hydroperoxide formation.
AB  - Soybean lipoxygenase-1 (SBLO-1) catalyzes the oxygenation of polyunsaturated
      fatty acids to produce conjugated diene hydroperoxides. Previous work from our
      laboratories has demonstrated that SBLO-1 will also catalyze the oxygenation of
      monounsaturated acids (Clapp, C. H., Senchak, S. E., Stover, T. J., Potter, T.
      C., Findeis, P. M., and Novak, M. J. (2001) Soybean Lipoxygenase-Mediated
      Oxygenation of Monounsaturated Fatty Acids to Enones, J. Am. Chem. Soc. 123, 747
      748). Interestingly, the products are alpha,beta-unsaturated ketones rather than
      the expected allylic hydroperoxides. In the present work, we provide evidence
      that the monoolefin substrates are initially converted to allylic hydroperoxides,
      which are subsequently converted to the enone products. The hydroperoxide
      intermediates can be trapped by reduction to the corresponding allylic alcohols
      with glutathione peroxidase plus glutathione or with SnCl2. Under some
      conditions, the hydroperoxide intermediates accumulate and can be detected by
      HPLC and peroxide assays. Kinetics measurements at low concentrations of [1-14C]
      9(Z)-octadecenoic acid indicate that oxygenation of this substrate at 25 degrees
      C, pH 9.0 occurs with kcat/Km = 1.6 (+/-0.1) x 10(2) M-1 s-1, which is about 105
      lower than kcat/Km for oxygenation of 9(Z),12(Z)-octadecadienoic acid (linoleic
      acid). Comparison of the activities of 9(Z)-octadecenoic acid and 12(Z)
      octadecenoic acid implies that the two double bonds of linoleic acid contribute
      almost equally to the C-H bond-breaking step in the normal lipoxygenase reaction.
      The results are consistent with the notion that SBLO-1 functionalizes substrates
      by a radical mechanism.

PMID- 17176112
TI  - Assembly of the stator in Escherichia coli ATP synthase. Complexation of alpha
      subunit with other F1 subunits is prerequisite for delta subunit binding to the N
      terminal region of alpha.
AB  - Alpha subunit of Escherichia coli ATP synthase was expressed with a C-terminal 6
      His tag and purified. Pure alpha was monomeric, was competent in nucleotide
      binding, and had normal N-terminal sequence. In F1 subunit
      dissociation/reassociation experiments it supported full reconstitution of
      ATPase, and reassociated complexes were able to bind to F1-depleted membranes
      with restoration of ATP-driven proton pumping. Therefore interaction between the
      stator delta subunit and the N-terminal residue 1-22 region of alpha occurred
      normally when pure alpha was complexed with other F1 subunits. On the other hand,
      three different types of experiments showed that no interaction occurred between
      pure delta and isolated alpha subunit. Unlike in F1, the N-terminal region of
      isolated alpha was not susceptible to trypsin cleavage. Therefore, during
      assembly of ATP synthase, complexation of alpha subunit with other F1 subunits is
      prerequisite for delta subunit binding to the N-terminal region of alpha. We
      suggest that the N-terminal 1-22 residues of alpha are sequestered in isolated
      alpha until released by binding of beta to alpha subunit. This prevents 1/1
      delta/alpha complexes from forming and provides a satisfactory explanation of the
      stoichiometry of one delta per three alpha seen in the F1 sector of ATP synthase,
      assuming that steric hindrance prevents binding of more than one delta to the
      alpha3/beta3 hexagon. The cytoplasmic fragment of the b subunit (bsol) did not
      bind to isolated alpha. It might also be that complexation of alpha with beta
      subunits is prerequisite for direct binding of stator b subunit to the F1-sector.

PMID- 17176113
TI  - Mechanism of adenomatous polyposis coli (APC)-mediated blockage of long-patch
      base excision repair.
AB  - Recently, we found an interaction between adenomatous polyposis coli (APC) and
      DNA polymerase beta (pol-beta) and showed that APC blocks strand-displacement
      synthesis of long-patch base excision repair (LP-BER) (Narayan, S., Jaiswal, A.
      S., and Balusu, R. (2005) J. Biol. Chem. 280, 6942-6949); however, the mechanism
      is not clear. Using an in vivo LP-BER assay system, we now show that the LP-BER
      is higher in APC-/- cells than in APC+/+ cells. In addition to pol-beta, the pull
      down experiments showed that the full-length APC also interacted with flap
      endonuclease 1 (Fen-1). To further characterize the interaction of APC with pol
      beta and Fen-1, we performed a domain-mapping of APC and found that both pol-beta
      and Fen-1 interact with a 138-amino acids peptide from the APC at the DRI-domain.
      Our functional assays showed that APC blocks pol-beta-mediated 1-nucleotide (1
      nt) as well as strand-displacement synthesis of reduced abasic, nicked-, or 1-nt
      gapped-DNA substrates. Further studies demonstrated that APC blocks 5'-flap
      endonuclease as well as the 5'-3' exonuclease activity of Fen-1 resulting in the
      blockage of LP-BER. From these results, we concluded that APC can have three
      different effects on the LP-BER pathway. First, APC can block pol-beta-mediated 1
      nt incorporation and strand-displacement synthesis. Second, APC can block LP-BER
      by blocking the coordinated formation and removal of the strand-displaced flap.
      Third, APC can block LP-BER by blocking hit-and-run synthesis. These studies will
      have important implications for APC in DNA damage-induced carcinogenesis and
      chemoprevention.

PMID- 17176114
TI  - The histone gene transcription factor HiNF-P stabilizes its cell cycle regulatory
      co-activator p220NPAT.
AB  - Orderly progression through the cell cycle requires the transcriptional
      activation of histone genes to support packaging of newly replicated DNA.
      Induction of human histone gene expression is mediated by a co-activation complex
      containing transcription factor HiNF-P and its cofactor p220NPAT. Here, using
      cells synchronized in S-phase and in mitosis, as well as serum-stimulated cells,
      we have investigated how HiNF-P is regulated during the cell cycle and examined
      its stability relative to p220NPAT. We find that while HiNF-P is maintained at
      steady-state levels throughout the cell cycle, both HiNF-P and p220NPAT are
      actively degraded by the proteasome pathway. Importantly, elevation of HiNF-P
      levels enhances the stability of its co-activator p220NPAT. The HiNF-P-dependent
      stabilization of p220NPAT may reinforce signaling through the cyclin
      E/CDK2/p220NPAT pathway and contribute to coordinate control of histone gene
      expression.

PMID- 17176116
TI  - Membrane interactions of dynorphins.
AB  - The dynorphins are primarily endogenous ligands to the kappa-opioid receptor, but
      a variety of non-opioid effects have also been observed, including direct effects
      on membranes. The peptides are rich in Arg residues, a characteristic feature of
      the cell-penetrating peptides. In this investigation, we have examined the
      interaction of the two peptides dynorphin A and dynorphin B with model membranes.
      A variety of NMR methods, as well as CD and fluorescence spectroscopy, have been
      used to characterize the structure of the two peptides and, more importantly, the
      position of the peptides in phospholipid bicelles. Both peptides interact to a
      large extent with both zwitterionic and partly negatively charged bicelles but
      are only marginally structured in either solvent. Dynorphin A was found to insert
      its N-terminus into the bilayer of the bicelle, while dynorphin B was found to
      reside on the surface of the bilayer. Despite the high degree of similarity in
      the sequence of the two peptides, it has previously been observed that dynorphin
      A has membrane perturbing effects and causes leakage of calcein from large
      unilamellar phospholipid vesicles while dynorphin B has no such effects. Our
      results provide a possible explanation for the difference in membrane
      perturbation.

PMID- 17176115
TI  - Specific and efficient binding of xeroderma pigmentosum complementation group A
      to double-strand/single-strand DNA junctions with 3'- and/or 5'-ssDNA branches.
AB  - Human XPA is an important DNA damage recognition protein in nucleotide excision
      repair (NER). We previously observed that XPA binds to the DNA lesion as a
      homodimer [Liu, Y., Liu, Y., Yang, Z., Utzat, C., Wang, G., Basu, A. K., and Zou,
      Y. (2005) Biochemistry 44, 7361-7368]. Herein we report that XPA recognized
      undamaged DNA double-strand/single-strand (ds-ssDNA) junctions containing ssDNA
      branches with binding affinity (Kd = 49.1 +/- 5.1 nM) much higher than its
      ability to bind to DNA damage. The recognized DNA junction structures include the
      Y-shape junction (with both 3'- and 5'-ssDNA branches), 3'-overhang junction
      (with a 3'-ssDNA branch), and 5'-overhang junction (with a 5'-ssDNA branch).
      Using gel filtration chromatography and gel mobility shift assays, we showed that
      the highly efficient binding appeared to be carried out by the XPA monomer and
      that the binding was largely independent of RPA. Furthermore, XPA efficiently
      bound to six-nucleotide mismatched DNA bubble substrates with or without DNA
      adducts including C8 guanine adducts of AF, AAF, and AP and the T[6,4]T
      photoproducts. Using a set of defined DNA substrates with varying degrees of DNA
      bending, we also found that the XPC-HR23B complex recognized DNA bending, whereas
      neither XPA nor the XPA-RPA complex could bind to bent DNA. We propose that,
      besides DNA damage recognition, XPA may also play a novel role in stabilizing,
      via its high affinity to ds-ssDNA junctions, the DNA strand opening surrounding
      the lesion for stable formation of preincision NER intermediates. Our results
      provide a plausible mechanistic interpretation for the indispensable requirement
      of XPA for both global genome and transcription-coupled repairs. Since ds-ssDNA
      junctions are common intermediates in many DNA metabolic pathways, the additional
      potential role of XPA in cellular processes is discussed.

PMID- 17176117
TI  - Domain organization and quaternary structure of the Saccharomyces cerevisiae
      silent information regulator 3 protein, Sir3p.
AB  - The silent information regulator protein 3 (Sir3p) functions in the initiation,
      propagation, and maintenance of transcriptionally silenced chromatin in
      Saccharomyces cerevisiae. To better understand the physicochemical basis for its
      effects on chromatin architecture, recombinant full-length S. cerevisiae Sir3p
      has been purified to near homogeneity on the large-scale and characterized by
      circular dichroism, limited protease digestion, and analytical
      ultracentrifugation. Results indicate that the Sir3p monomer has a unique
      tripartite domain organization, including a nearly 300-amino-acid residue stretch
      of intrinsically disordered residues that lies internal to its structured N- and
      C-terminal regions. Sir3p self-associates extensively in moderate salt and at
      micromolar protein concentrations producing a broad range of oligomers that
      sediment from 8 to in excess of 85 S. These results provide new insight into
      Sir3p domain organization and quaternary structure and support a nucleosome
      bridging model for Sir3p-dependent regulation of chromatin architecture.

PMID- 17176119
TI  - The therapeutic potential of intrabodies in neurologic disorders: focus on
      Huntington and Parkinson diseases.
AB  - Single-chain Fv and single-domain antibodies retain the binding specificity of
      full-length antibodies but they can be cloned, selected, engineered, and
      manipulated as genes. When expressed intracellularly in mammalian cells these
      intracellular antibodies, or intrabodies, have the potential to alter the
      folding, interactions, modifications, or subcellular localization of their
      targets. These reagents have previously been developed as therapeutics against
      cancer and HIV. Since misfolded and accumulated intracellular proteins
      characterize several major neurodegenerative disorders, including Huntington
      disease (HD) and Parkinson disease, these disorders are prime candidates for
      intrabody therapy. In this article we review the extension of intrabody
      technology to the nervous system. Studies of HD have been used to develop the
      approach and anti-synuclein strategies are in the early stages of development.
      Such neurodegenerative diseases are therefore poised for engineered antibody
      approaches, which can provide a pipeline of novel therapeutics and new drug
      discovery tools.

PMID- 17176120
TI  - Evolving strategies for the prevention of influenza infection: potential for
      multistrain targeting.
AB  - Approved influenza vaccines based on the induction of antibodies to hemagglutinin
      are strain specific and cumbersome to manufacture. Several alternative vaccine
      strategies based on the induction of humoral responses against the external
      domain of the M2 protein, as well as cellular responses against nucleoprotein,
      have the potential to target multiple strains of influenza. A universal vaccine
      would be a major advancement in the prevention of influenza infection as it would
      alleviate the need for tailored vaccines to control seasonal influenza epidemics
      while simultaneously providing a level of protection against potential pandemic
      strains.

PMID- 17176121
TI  - Progress in the development of immune-based therapies for type 1 diabetes
      mellitus.
AB  - Between ten and twenty million people worldwide have type 1 diabetes mellitus
      (T1DM), which has previously been called juvenile diabetes, childhood diabetes,
      and insulin-dependent diabetes mellitus. T1DM is undoubtedly a multifactorial
      disease affecting predisposed individuals with genetic susceptibilities; it is
      also associated with environmental factors leading to unbalanced immune
      responses. This chronic disorder is caused by auto-aggressive T lymphocytes
      entering the pancreatic islets of Langerhans where they destroy the insulin
      producing beta-cells. A wide variety of immuno-interventions cure T1DM
      effectively in different animal models when given early in disease development.
      However, few of these interventions are efficacious in humans at a later stage of
      the disease. Indeed, only three immunotherapeutic compounds have demonstrated
      both safety and efficacy in phase II/III clinical trials. Although much time and
      resources have been spent on generating potent immune therapies, none of the
      patients enrolled in these trials have achieved normoglycemia in the absence of
      insulin injections. Many reasons can account for such a disappointing conclusion.
      Firstly, the dynamics of disease pathogenesis differs significantly from patient
      to patient, which directly impacts the therapeutic efficacy. Also, at trial
      entry, the percentage of remaining pancreatic beta-cells in T1DM patients often
      reflects the odds of responding positively to treatment. Based on the knowledge
      we have gained from preclinical studies and clinical trials, several steps have
      been made in the development of safer and more efficient immune-based therapies.
      There are, however, a number of concerns that should be addressed in order to
      improve future therapeutic strategies.

PMID- 17176122
TI  - BioMEMS sensor systems for bacterial infection detection : progress and
      potential.
AB  - The spread of drug-resistant bacteria represents a growing worldwide health
      problem. The most efficient way to fight drug-resistant bacteria is to detect
      their colonies, identify their type, monitor their growth, and destroy them
      before they reach the human body. A gravimetric biomedical micro-electro
      mechanical sensor (BioMEMS) system operating in the pico-gram range (10(-)(12)
      g/cm(2)) has been proposed for detecting growth of drug-resistant bacterial
      colonies. The sensor is based on a MEMS metal-coated thin piezoelectric membrane
      resonator. A combination of shear horizontal surface acoustic (SHSAW), Bleustein
      Gulyaev, skimming and 'leaky' waves, generated in the resonator, are highly
      sensitive to mass, density, viscoelastic, and electrochemical changes at the
      resonator/bacteria interface. Measuring resonant frequency shifts of the
      composite resonator provides information about the mass and type of the bacterium
      colony growing on the resonator.

PMID- 17176123
TI  - Effects of site-specific polyethylene glycol modification of recombinant human
      granulocyte colony-stimulating factor on its biologic activities.
AB  - BACKGROUND: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is
      a long-chain cytokine that is administered to stimulate the production of white
      blood cells (WBCs) to reduce the risk of serious infection in immunocompromized
      patients. However, to achieve sustained stimulation of WBC production, rhG-CSF
      must be administered frequently, thus limiting its clinical use. METHODS: We
      conjugated rhG-CSF with linear monomethoxy-polyethylene glycol (PEG) maleimide at
      amino acid residue Cys(17) to test our hypothesis that this could extend the in
      vivo half-life of rhG-CSF in blood. RESULTS: The mono-PEG rhG-CSF became more
      stable to pH, temperature, and enzyme degradation in vitro, and had
      granulopoietic activity that was superior to the unmodified form in vivo. The
      granulopoietic activity of PEG-G-CSF was 2.82-fold greater than that of
      unmodified G-CSF. CONCLUSIONS: These results indicate that the thiol-specific
      PEGylation remarkably prolonged the half-life of rhG-CSF and represents a novel
      strategy to address the more clinically acceptable therapeutic application of
      hemopoietic growth factor.

PMID- 17176124
TI  - An experimental model for the study of lymphedema and its response to therapeutic
      lymphangiogenesis.
AB  - BACKGROUND: Evaluation of the efficacy of molecular treatment strategies for
      lymphatic vascular insufficiency requires a suitable preclinical animal model.
      Ideally, the model should closely replicate the untreated human disease in its
      pathogenesis and pathological expression. OBJECTIVE: We have undertaken a study
      of the time course of the development and resolution of acquired, experimental
      lymphedema and of its responses to vascular endothelial growth factor (VEGF)-C
      lymphangiogenesis in the mouse tail model. STUDY DESIGN: We provoked post
      surgical lymphedema in the mouse tail model and assessed the effects of
      exogenously administered human recombinant VEGF-C. Quantitative assessment of
      immune traffic function was performed through sequential in vivo bioluminescent
      imaging. RESULTS: In untreated lymphedema, tail edema was sustained until day 21.
      Exogenous administration of human recombinant VEGF-C produced a significant
      decrease in volume. Untreated lymphedema in the mouse tail model was
      characterized by the presence of dilated cutaneous lymphatics, marked acute
      inflammatory changes, and hypercellularity; VEGF-C produced a substantial
      reversion to the normal pattern, with notable regression in the size and number
      of cutaneous lymphatic vessels that express lymphatic vessel endothelial
      hyaluronan receptor-1 (LYVE-1). In vivo imaging confirmed the presence of an
      impairment of immune traffic in lymphedema that was ameliorated after VEGF-C
      administration. CONCLUSION: The post-surgical murine tail model of lymphedema
      closely simulates attributes of human lymphedema and provides the requisite
      sensitivity to detect therapeutically induced functional and structural
      alterations. It can, therefore, be used as an investigative platform to assess
      mechanisms of disease and its responses to candidate therapies, such as
      therapeutic lymphangiogenesis.

PMID- 17176125
TI  - Reduced-antigen, combined diphtheria, tetanus, and acellular pertussis vaccine
      (Boostrix): a review of its use as a single-dose booster immunization.
AB  - Reduced-antigen, combined diphtheria, tetanus, and acellular pertactin-containing
      pertussis vaccine (dTpa; Boostrix) contains reduced quantities of the same
      toxoids/antigens found in a diphtheria, tetanus, and acellular pertussis vaccine
      (DTPa; Infanrix) used for the primary immunization series in children. A single
      dose of dTpa (Boostrix) is indicated for booster vaccination against diphtheria,
      tetanus, and pertussis in individuals aged >or=4 years in Europe and Canada, in
      individuals aged >or=10 years in Australia, and in adolescents aged 10-18 years
      in the US.A single booster dose of dTpa (Boostrix) was safe and highly
      immunogenic for all its component toxoids/antigens when administered to adults,
      adolescents (including those previously unvaccinated), and children aged >or=4
      years in clinical trials conducted in various countries worldwide. It was also
      well tolerated, as was a second (repeat) dose administered to a small number of
      adolescents who had previously received the vaccine as a preschool booster.
      Vaccinees generally reported a low incidence of severe/grade 3, solicited, local
      and general adverse events during the 1-month postvaccination period.Current
      recommendations for dTpa usage vary from country to country; they include one
      dose only in adolescence or adulthood (e.g. Australia, Canada, France,
      Switzerland, and the US), one dose at preschool age and one in adolescence
      (Germany), and one dose in adolescence followed by regular (10-year) doses during
      adulthood (Austria). Available data support the use of dTpa (Boostrix) in place
      of the combined diphtheria, tetanus, whole-cell pertussis vaccine (DTwP) or DTPa
      booster dose in preschool children and/or the reduced-antigen, combined
      diphtheria, tetanus vaccine (Td) booster dose in adolescents, as well as in place
      of a regular Td booster dose in adults who have not previously received the
      vaccine.

PMID- 17176126
TI  - A full-configuration interaction "nuclear orbital" method to study doped 3HeN
      clusters (N< or =4).
AB  - An efficient full configuration interaction (FCI) treatment, based on the Jacobi
      Davidson algorithm, is developed in order to study small doped (3)He(N) clusters.
      The state of each He atom in a given cluster is described by a set of wave
      functions which by extention of the quantum-chemistry notation are caller here
      "nuclear orbitals". The FCI treatment is applied to the calculation of binding
      energies and helium natural orbitals of (3)He(N)...Br(2)(X) complexes. In
      agreement with our previous calculations using a Hartree-Fock approach [Phys.
      Rev. Lett. 93, 053401 (2004)], in which the He-He interaction is modified at
      small distances to account for short-range correlation effects, the lowest-energy
      states of each multiplet are found to be very close in energy. The natural
      orbital analysis, in turn, indicates the adequacy of the "nuclear orbital"
      approach in these systems.

PMID- 17176127
TI  - Experimental investigation of the Soret effect in acetone/water and
      dimethylsulfoxide/water mixtures.
AB  - The thermal diffusion behavior of acetone/water and dimethylsulfoxide(DMSO)/water
      mixtures has been experimentally investigated by a transient holographic grating
      technique named thermal diffusion forced Rayleigh scattering (TDFRS). For both
      systems a sign change of the Soret coefficient S(T) with varying water content
      has been predicted by simulations [C. Nieto Draghi et al., J. Chem. Phys. 122,
      114503 (2005)]. The sign change of S(T) is confirmed by the experiment. Except
      for equimolar concentrations of acetone/water the agreement between the
      experimental and simulation data is reasonable.

PMID- 17176129
TI  - Exploring the effect of anharmonicity of molecular vibrations on thermodynamic
      properties.
AB  - Thermodynamic properties of selected small and medium size molecules were
      calculated using harmonic and anharmonic vibrational frequencies. Harmonic
      vibrational frequencies were obtained by normal mode analysis, whereas anharmonic
      ones were calculated using the vibrational self-consistent field (VSCF) method.
      The calculated and available experimental thermodynamic data for zero point
      energy, enthalpy, entropy, and heat capacity are compared. It is found that the
      anharmonicity and coupling of molecular vibrations can play a significant role in
      predicting accurate thermodynamic quantities. Limitations of the current VSCF
      method for low frequency modes have been partially removed by following normal
      mode displacements in internal, rather than Cartesian, coordinates.

PMID- 17176128
TI  - Ab initio treatment of time-resolved x-ray scattering: application to the
      photoisomerization of stilbene.
AB  - In this work we present a general theoretical outline for calculating time
      dependent x-ray scattering signal changes from first principles. We derive a
      formalism for the description of atom-atom correlation functions as Fourier
      transforms of quantum-chemically calculated electron densities and show their
      proportionality to the molecular form factor. The formalism derived in this work
      is applied to the photoisomerization of stilbene. We can demonstrate that wide
      angle x-ray scattering offers a possibility to study the changes in electron
      densities in nonperiodic complex systems, which renders it a suitable technique
      for the investigation of (bio)organic systems.

PMID- 17176130
TI  - Calculation of nonadiabatic couplings with restricted open-shell Kohn-Sham
      density-functional theory.
AB  - This paper generalizes the recently proposed approaches for calculating the
      derivative couplings between adiabatic states in density-functional theory (DFT)
      based on a Slater transition-state density to transitions such as singlet-singlet
      excitations, where a single-determinant ansatz is insufficient. The proposed
      approach is based on restricted open-shell Frank et al. [J. Chem. Phys. 108, 4060
      (1998)] theory used to describe a spin-adapted Slater transition state. To treat
      the dependence of electron-electron interactions on the nuclear positions,
      variational linear-response density-functional perturbation theory is generalized
      to reference states with an orbital-dependent Kohn-Sham Hamiltonian and
      nontrivial occupation patterns. The methods proposed in this paper are not
      limited to the calculation of derivative coupling vectors, but can also be used
      for the calculation of other transition matrix elements. Moreover, they can be
      used to calculate the linear response of open-shell systems to arbitrary external
      perturbations in DFT.

PMID- 17176131
TI  - Using the thermal Gaussian approximation for the Boltzmann operator in
      semiclassical initial value time correlation functions.
AB  - The thermal Gaussian approximation (TGA) recently developed by Frantsuzov et al.
      [Chem. Phys. Lett. 381, 117 (2003)] has been demonstrated to be a practical way
      for approximating the Boltzmann operator exp(-betaH) for multidimensional
      systems. In this paper the TGA is combined with semiclassical (SC) initial value
      representations (IVRs) for thermal time correlation functions. Specifically, it
      is used with the linearized SC-IVR (LSC-IVR, equivalent to the classical Wigner
      model), and the "forward-backward semiclassical dynamics" approximation developed
      by Shao and Makri [J. Phys. Chem. A 103, 7753 (1999); 103, 9749 (1999)]. Use of
      the TGA with both of these approximate SC-IVRs allows the oscillatory part of the
      IVR to be integrated out explicitly, providing an extremely simple result that is
      readily applicable to large molecular systems. Calculation of the force-force
      autocorrelation for a strongly anharmonic oscillator demonstrates its accuracy,
      and calculation of the velocity autocorrelation function (and thus the diffusion
      coefficient) of liquid neon demonstrates its applicability.

PMID- 17176132
TI  - Linear-scaling calculation of static and dynamic polarizabilities in Hartree-Fock
      and density functional theory for periodic systems.
AB  - We present a linear-scaling method for analytically calculating static and
      dynamic polarizabilities with Hartree-Fock and density functional theory, using
      Gaussian orbitals and periodic boundary conditions. Our approach uses the direct
      space fast multipole method to evaluate the long-range Coulomb contributions. For
      exact exchange, we use efficient screening techniques developed for energy
      calculations. We then demonstrate the capabilities of our approach with benchmark
      calculations on one-, two-, and three-dimensional systems.

PMID- 17176133
TI  - Influence of the exchange screening parameter on the performance of screened
      hybrid functionals.
AB  - This work reexamines the effect of the exchange screening parameter omega on the
      performance of the Heyd-Scuseria-Ernzerhof (HSE) screened hybrid functional. We
      show that variation of the screening parameter influences solid band gaps the
      most. Other properties such as molecular thermochemistry or lattice constants of
      solids change little with omega. We recommend a new version of HSE with the
      screening parameter omega=0.11 bohr(-1) for further use. Compared to the original
      implementation, the new parametrization yields better thermochemical results and
      preserves the good accuracy for band gaps and lattice constants in solids.

PMID- 17176134
TI  - Electrostatic interactions in dissipative particle dynamics using the Ewald sums.
AB  - The electrostatic interactions in dissipative particle dynamics (DPD) simulations
      are calculated using the standard Ewald [Ann. Phys. 64, 253 (1921)] sum method.
      Charge distributions on DPD particles are included to prevent artificial ionic
      pair formation. This proposal is an alternative method to that introduced
      recently by Groot [J. Chem. Phys. 118, 11265 (2003)] where the electrostatic
      field was solved locally on a lattice. The Ewald method is applied to study a
      bulk electrolyte and polyelectrolyte-surfactant solutions. The structure of the
      fluid is analyzed through the radial distribution function between charged
      particles. The results are in good agreement with those reported by Groot for the
      same systems. We also calculated the radius of gyration of a polyelectrolyte in
      salt solution as a function of solution pH and degree of ionization of the chain.
      The radius of gyration increases with the net charge of the polymer in agreement
      with the trend found in static light scattering experiments of polystyrene
      sulfonate solutions.

PMID- 17176135
TI  - Significant change of alignment effect by dimer formation in the dissociative
      energy transfer reaction of Ar(3P2)+(N2O)n and (H2O)n.
AB  - An alignment effect in the dissociative energy transfer reaction of
      Ar((3)P(2))+(X(2)O)(n)(X=N,H) was directly measured using an oriented
      Ar((3)P(2),M(J)=2) beam. The chemiluminescence intensity of N(2)(B,(3)Pi(g)) for
      (N(2)O)(n) and OH(A,(2)Sigma(+)) for (H(2)O)(n) was measured as a function of the
      magnetic orientation field direction in the collision frame. The relative
      reaction cross section for each magnetic substate in the collision frame,
      sigma(M(J) (') ), was determined. In both the reaction systems, it is observed
      that the dimer formation significantly enhances the alignment effect and
      decreases the reactivity, especially for sigma|1| and sigma|2|. A significant
      contribution of rank 4 moment is recognized in the dimer reaction.

PMID- 17176136
TI  - Thermodynamics of water octamer in a uniform electric field.
AB  - We study the water octamer in a uniform electric field using the all-exchanges
      parallel tempering Monte Carlo method in the canonical ensemble. The heat
      capacity, quenched energy configurations, and the order parameter Q(4) are
      employed to understand the phase changes observed as a function of temperature
      and the strength of the applied electric field. At a low field strength of 0.1 V
      A(-1) a solidlike to liquidlike "melting" transition is detected. The
      corresponding heat capacity peak appears around 206 K, where Q(4) shows a
      significant change of slope. For E> or =0.5 V A(-1) such features are absent.
      However, at E=0.5 V A(-1) we find a solidlike to solidlike transition between
      cubic and extended structures around T approximately 25 K.

PMID- 17176137
TI  - The A 1Sigmau+ state of K2 up to the dissociation limit.
AB  - We report an experimental study of the K(2) A (1)Sigma(u) (+) state. Long-range
      levels up to the dissociation limit were observed in a two laser spectroscopic
      experiment using a highly collimated molecular beam. We derive an analytical
      potential energy curve for the complete A state including long-range dispersion
      terms. From these, we obtain radiative atomic lifetimes of 26.74(3) ns for the
      4p(1/2) state and 26.39(3) ns for the 4p(3/2) state of (39)K. The dissociation
      energy of the X (1)Sigma(g) (+) ground state with respect to v=0, J=0 is found to
      be D(0)=4404.808(4) cm(-1).

PMID- 17176138
TI  - Photodissociation dynamics of ClN3 at 193 nm.
AB  - Photofragment translational spectroscopy was used to identify the primary and
      secondary reaction pathways in 193 nm photodissociation of chlorine azide
      (ClN(3)) under collision-free conditions. Both the molecular elimination
      (NCl+N(2)) and the radical bond rupture channel (Cl+N(3)) were investigated and
      compared with earlier results at 248 nm. The radical channel strongly dominates,
      just as at 248 nm. At 193 nm, the ClN(3) (C (1)A(")) state is excited, rather
      than the B (1)A(') state that is accessed at 248 nm, resulting in different
      photofragment angular distributions. The chlorine translational energy
      distribution probing the dynamics of the radical bond rupture channel shows three
      distinct peaks, with the two fastest peaks occurring at the same translational
      energies as the two peaks seen at 248 nm that were previously assigned to linear
      and "high energy" N(3). Hence, nearly all the additional photon energy relative
      to 248 nm appears as N(3) internal excitation rather than as translational
      energy, resulting in considerably more spontaneous dissociation of N(3) to
      N(2)+N.

PMID- 17176139
TI  - Infrared photodissociation spectroscopy of protonated ammonia cluster ions,
      NH4+(NH3)n (n=5-8), by using infrared free electron laser.
AB  - Infrared photodissociation action spectra of protonated ammonia cluster ions,
      NH(4) (+)(NH(3))(n) (n=5-8), were measured in the range of 1020-1210 cm(-1) by
      using a tunable infrared free electron laser. Analyses by the density functional
      theory (DFT) show that the spectral features observed can be assigned to the
      nu(2) vibrational mode of the NH(3) molecules in NH(4) (+)(NH(3))(n). Size
      dependence of the spectra supports structural models obtained by the DFT
      calculations, in which the NH(4) (+) ion is solvated by the four nearest-neighbor
      NH(3) molecules. For NH(4) (+)(NH(3))(5), the spectrum between 1000 and 1700 cm(
      1) was measured. The nu(4) bands of the NH(3) molecules and the NH(4) (+) ion
      were found in the range of 1420-1700 cm(-1).

PMID- 17176140
TI  - Potential energy surface and MULTIMODE vibrational analysis of C2H3+.
AB  - A full dimensional, ab initio-based semiglobal potential energy surface for
      C(2)H(3) (+) is reported. The ab initio electronic energies for this molecule are
      calculated using the spin-restricted, coupled cluster method restricted to single
      and double excitations with triples corrections [RCCSD(T)]. The RCCSD(T) method
      is used with the correlation-consistent polarized valence triple-zeta basis
      augmented with diffuse functions (aug-cc-pVTZ). The ab initio potential energy
      surface is represented by a many-body (cluster) expansion, each term of which
      uses functions that are fully invariant under permutations of like nuclei. The
      fitted potential energy surface is validated by comparing normal mode frequencies
      at the global minimum and secondary minimum with previous and new direct ab
      initio frequencies. The potential surface is used in vibrational analysis using
      the "single-reference" and "reaction-path" versions of the code MULTIMODE.

PMID- 17176141
TI  - Experimental and ab initio study of a new D 1Deltag state of the C3 radical.
AB  - We report here the first observation of the D (1)Delta(g) state of the C(3)
      radical, which provides the first comprehensively analyzed example of the dynamic
      Renner-Teller splitting in Delta symmetry. Two color double resonance
      spectroscopy via the A (1)Pi(u) state was employed to experimentally probe an
      extensive range of vibronic levels in this D (1)Delta(g) state, covering all
      three modes of vibration of C(3). The analysis was supported by ab initio
      potential energy surface calculations on the C(3) radical to outline the lowest
      eight singlet electronic states. Two methods were used to analyze the Renner
      Teller effect. The first method is an empirical Hamiltonian based on normal
      modes, using harmonic oscillator functions as a basis, with Renner-Teller and
      other terms added as required, which allows conventional vibrational parameters
      to be determined. The second is a much larger program that uses the exact kinetic
      energy operator for a triatomic molecule to calculate vibronic energy levels
      directly from the Renner-Teller pair of potential energy surfaces. Both methods
      give a good fit to the experimental results, with only a small adjustment to the
      ab initio surfaces required for the latter. One of the overall conclusions is
      that the Renner-Teller effect is rather smaller in the D (1)Delta(g) state than
      in the A (1)Pi(u) state.

PMID- 17176142
TI  - Reaction of chlorine atom with trichlorosilane from 296 to 473 K.
AB  - The reaction of trichlorosilane (HSiCl(3)) with atomic chlorine (Cl) has been
      investigated by using infrared kinetic spectroscopy of the HCl product. The
      overall second order rate constant for the reaction has been determined as a
      function of temperature by using pseudo-first-order kinetic methods. Formation of
      HCl (nu=0) was monitored on the (nu=1<--0) R(2) line at 2944.914 cm(-1) and that
      of HCl (nu=1) on the (nu=2<--1) R(2) line at 2839.148 cm(-1). The overall second
      order rate constant was determined to be (2.8+/-0.1)x10(-11) cm(3) molecule(-1)
      s(-1) at 296 K. The rate constant shows no pressure dependence and decreases
      slightly with increased temperature [k=(2.3+/-0.2)x10(-11)e((66+/-3)/T) cm(3)
      molecule(-1) s(-1)]. Substantial vibrational excitation is measured in the HCl
      product, with the fraction of HCl (nu=1)/HCl (total)=0.41+/-0.08. These
      observations are consistent with the reaction being a barrierless hydrogen
      abstraction reaction. The experimental results are supported by ab initio quantum
      chemical calculations that show the transition state for abstraction to lie below
      the energy of the reactants, in disagreement with previously published
      calculations.

PMID- 17176143
TI  - Analysis of the transverse and the longitudinal pseudodiffusion of CO2 in sub-
      and supercritical states: a molecular-dynamics analysis.
AB  - We have performed molecular-dynamics simulations of CO(2) system along the gas
      liquid coexistence curve and on the isochore 94.22 cm(3) mol(-1) (which
      corresponds to the critical isochore). The calculation has been carried out in
      order to analyze the diffusion of CO(2) and particularly to figure out how the
      diffusion coefficient may be decomposed along the molecular axes. This makes it
      possible to analyze the anisotropy of the diffusion along these axes and to shed
      light on the microscopic changes which accompany such behavior. This anisotropy
      is traced back to the effect of the translation-rotation coupling (TRC) along the
      molecular axes. Along the liquid-gas coexistence curve, the pseudolongitudinal
      diffusion is found to be more rapid than the transverse one. The opposite trend
      is found along the isochore 94.22 cm(3) mol(-1). The role of the local structure
      was explored by calculating intermediate scattering function and the
      autocorrelation functions for the forces acting along the molecular axes. It is
      shown that the strength of the TRC effect is correlated to the difference between
      the relaxation times of the local structure, that of the reorientation along the
      molecular axes, and that of the translational motion. The analysis of the
      correlation time and the average mean square force along the longitudinal and
      transverse directions confirms the anisotropy of the local environment that
      determines the translational dynamics of a molecule.

PMID- 17176144
TI  - Angular momentum dependent friction slows down rotational relaxation under
      nonequilibrium conditions.
AB  - It has recently been shown that relaxation of the rotational energy of hot
      nonequilibrium photofragments (i) slows down significantly with the increase of
      their initial rotational temperature and (ii) differs dramatically from the
      relaxation of the equilibrium rotational energy correlation function, manifesting
      thereby the breakdown of the linear response description [A. C. Moskun et al.,
      Science 311, 1907 (2006)]. We demonstrate that this phenomenon may be caused by
      the angular momentum dependence of rotational friction. We have developed the
      generalized Fokker-Planck equation whose rotational friction depends upon angular
      momentum algebraically. The calculated rotational correlation functions
      correspond well to their counterparts obtained via molecular dynamics simulations
      in a broad range of initial nonequilibrium conditions. It is suggested that the
      angular momentum dependence of friction should be taken into account while
      describing rotational relaxation far from equilibrium.

PMID- 17176145
TI  - Calculation of the absolute thermodynamic properties of association of host-guest
      systems from the intermolecular potential of mean force.
AB  - The authors report calculations of the intermolecular potential of mean force
      (PMF) in the case of the host-guest interaction. The host-guest system is defined
      by a water soluble calixarene and a cation. With an organic cation such as the
      tetramethylammonium cation, the calixarene forms an insertion complex, whereas
      with the Lanthane cation, the supramolecular assembly is an outer-sphere complex.
      The authors apply a modified free energy perturbation method and the force
      constraint technique to establish the PMF profiles as a function of the
      separation distance between the host and guest. They use the PMF profile for the
      calculation of the absolute thermodynamic properties of association that they
      compare to the experimental values previously determined. They finish by giving
      some structural features of the insertion and outer-sphere complexes at the Gibbs
      free energy minimum.

PMID- 17176146
TI  - Coherent control of cross-peaks in chirality-induced two-dimensional optical
      signals of excitons.
AB  - Polarization tuning of the interference of chirality-induced tensor components is
      used to simulate the suppression of diagonal peaks and amplification of cross
      peaks in femtosecond two-dimensional photon echo signals of excitons in a chiral
      porphyrin dimer. Superpositions of various tensor components which generate the
      optimized signals are constructed using a genetic learning algorithm. Exciton
      couplings and bath correlations may be extracted from these highly resolved
      signals.

PMID- 17176147
TI  - Neutron diffraction and simulation studies of the exocyclic hydroxymethyl
      conformation of glucose.
AB  - The techniques of neutron diffraction with isotopic substitution (NDIS) and
      molecular dynamics (MD) simulations have been used to examine the rotational
      conformation of the exocyclic hydroxymethyl group of D-glucopyranose. First order
      H/D NDIS experiments were performed on the H6 position in 3m aqueous glucose
      solutions where the average coherent scattering length of the exchangeable
      hydrogen atoms was zero (i.e., all correlations between exchangeable hydrogen
      atoms and other atoms cancel and thus are not present in the scattering data).
      This H6 experimental result suggests that no single conformation for the C4-C5-C6
      O6 dihedral reproduces the observed scattering data well, but that a mixture of
      the gg and gt conformations, which has been suggested by NMR experiments, gives a
      reasonable agreement between the MD and experimental data.

PMID- 17176148
TI  - Shape and stability of two-dimensional lipid domains with dipole-dipole
      interactions.
AB  - We study the general energy and shape of the two-dimensional solid monolayer
      domains with the dipole-dipole interactions. Compared with the domain energy
      without tilted dipole moments [M. Iwamoto and Z. C. Ou-Yang, Phys. Rev. Lett. 93,
      206101 (2004)], the general dipolar energy is not only shape and size but also
      boundary orientation dependent. The general shape equation derived by this energy
      using variational approach predicts a circular solution and an equilibrium shape
      grown from this circle. In particular, the latter is composed of two branches: a
      translation-induced growth of all odd harmonic modes and a pressure-induced
      cooperative deformation by all even harmonic modes. The good qualitative
      agreement between our prediction and the experimental observations shows the
      validity of the present theory.

PMID- 17176149
TI  - Influence of submonolayer sodium adsorption on the photoemission of the
      Cu(111)/water ice surface.
AB  - Photoemission from an ice film deposited on Cu(111) as a function of thickness
      has been observed in the presence and absence of sodium atoms at the surface
      vacuum interface. For either adsorbate alone and photon energies below 4 eV, two
      photon photoemission from the Cu(111) substrate dominates. The Cu(111)
      photoelectron spectrum is perturbed by low coverages of Na, and its intensity is
      strongly attenuated by a few monolayers of ice. For a low density amorphous ice
      film, strong charging effects are observed. For ice films annealed to yield
      either the dense amorphous or crystalline phase, this effect is absent.
      Deposition of only 0.02 monolayer of Na leads to a dramatic decrease in the
      threshold for photoemission to 2.3+/-0.2 eV. Thus, photoelectrons are generated
      by visible radiation in a one-photon process with a cross section that exceeds
      10(-18) cm(2). The initial state for the photoemission is identified as a
      metastable surface trapped electron, which decays thermally with an activation
      energy of 10+/-2 kJ mol(-1). Quantum calculations are described which support
      this model and show that the Na atom is accommodated in the first layer of the
      ice surface.

PMID- 17176150
TI  - Reduced density matrix quantum approach for particle trapping and sticking on
      corrugated moving surfaces.
AB  - A short time propagation algorithm for the reduced density matrix is derived to
      model the interaction of a quantum particle with a moving corrugated surface. The
      algorithm includes dissipative terms, which can be derived directly from the full
      Hamiltonian. The scattering of He from a corrugated Cu surface is examined as a
      function of incident energy and angle and the temperature of the substrate, with
      a focus on the nature of trapping. It is found that corrugation can make a
      significant contribution to trapping, even on a metal surface. Energy exchange
      with the phonons is shown to significantly modify the nature of diffraction
      mediated selective adsorption.

PMID- 17176151
TI  - Mixed protonic-electronic conduction and dielectric response in layered vanadyl
      phosphate nanocomposites.
AB  - The layered vanadyl phosphate, VOPO(4)2H(2)O, is employed to prepare nanosized
      conducting polypyrrole by redox intercalation method. Transport and dielectric
      properties of various compositions have been investigated by impedance technique
      over a temperature range of 300-120 K. Grain boundary conductivity is larger than
      the bulk conductivity. The conductivity reveals a discontinuity at about 212-235
      K. The conductivity is predominantly ionic at high temperature and electronic at
      low temperature. The dielectric spectra reveal a peak in the frequency range up
      to 2 MHz for higher concentration of intercalated polypyrrole. The activation
      energy of conductivity relaxation is different from that of total conductivity
      derived from the impedance plot.

PMID- 17176152
TI  - Deuteration-induced scission of C58 oligomers.
AB  - The reaction of solid C(58) films with atomic deuterium to yield
      deuterofullerenes, C(58)D(x), has been investigated by thermal desorption
      spectroscopy coupled with mass spectrometric detection, ultraviolet
      photoionization spectroscopy (21.2 eV), and atomic force microscopy (AFM). The
      average composition of the deuterofullerenes created depends on deuterium dose,
      beam flux, and surface temperature. Low deuterium exposures at room temperature
      yield predominantly C(58)D(6-8) cages. Saturation exposures at room temperature
      yield mass spectra peaked at C(58)D(26). After saturation exposures at elevated
      surface temperatures (approximately 500 K), the (subsequently) desorbed material
      reveals a comparatively narrow mass spectral distribution centered at C(58)D(30).
      Deuteration is associated with cleavage of covalent cage-cage bonds in the
      starting C(58) oligomer material, as evidenced by a considerable lowering of the
      sublimation energies of C(58)D(x) compared to desorption of C(58) desorbed from
      pure oligomer films. Correspondingly, AFM images reveal a D-induced, thermally
      activated transition from dendritic C(58) oligomer islands into smooth-rimmed
      islands composed of deuterated cages. Deuterated films exhibit a significantly
      lower work function than bare C(58) films. Progressing deuteration also gradually
      raises the surface ionization potential.

PMID- 17176153
TI  - A time correlation function theory describing static field enhanced third order
      optical effects at interfaces.
AB  - Sum vibrational frequency spectroscopy, a second order optical process, is
      interface specific in the dipole approximation. At charged interfaces, there
      exists a static field, and as a direct consequence, the experimentally detected
      signal is a combination of enhanced second and static field induced third order
      contributions. There is significant evidence in the literature of the
      importance/relative magnitude of this third order contribution, but no previous
      molecularly detailed approach existed to separately calculate the second and
      third order contributions. Thus, for the first time, a molecularly detailed time
      correlation function theory is derived here that allows for the second and third
      order contributions to sum frequency vibrational spectra to be individually
      determined. Further, a practical, molecular dynamics based, implementation
      procedure for the derived correlation functions that describe the third order
      phenomenon is also presented. This approach includes a novel generalization of
      point atomic polarizability models to calculate the hyperpolarizability of a
      molecular system. The full system hyperpolarizability appears in the time
      correlation functions responsible for third order contributions in the presence
      of a static field.

PMID- 17176154
TI  - Photochemistry on ultrathin metal films: strongly enhanced cross sections for NO2
      on Ag/Si(100).
AB  - The surface photochemistry of NO(2) on ultrathin Ag(111) films (5-60 nm) on
      Si(100) substrates has been studied. NO(2), forming N(2)O(4) on the surface,
      dissociates to release NO and NO(2) into the gas phase with translational
      energies exceeding the equivalent of the sample temperature. An increase of the
      photodesorption cross section is observed for 266 nm light when the film
      thickness is decreased below 30 nm despite the fact that the optical absorptivity
      decreases. For 4.4 nm film thickness this increase is about threefold. The data
      are consistent with a similar effect for 355 nm light. The reduced film thickness
      has no significant influence on the average translation energy of the desorbing
      molecules or the branching into the different channels. The increased
      photodesorption cross section is interpreted to result from photon absorption in
      the Si substrate producing electrons with no or little momenta parallel to the
      surface at energies where this is not allowed in Ag. It is suggested that these
      electrons penetrate through the Ag film despite the gap in the surface projected
      band structure.

PMID- 17176155
TI  - Loss of coherence in a population of diffusively coupled oscillators.
AB  - The authors investigate the relationship between the natural frequency
      distribution of diffusively coupled chemical oscillators and their entrainment by
      pacemakers. The system consists of micrometer-sized catalyst beads which are
      coupled to their neighbors by diffusion of the activator/inhibitor species
      through the catalyst-free Belousov-Zhabotinsky (BZ) reaction solution. The
      frequency distribution is measured as a function of the beads' number of
      neighbors. With the maximum number of neighbors, either target waves or
      disordered patterns are observed in the reaction domain and there is a shift to
      higher frequencies than those observed in the natural frequency distribution. The
      loss of coherence between neighbor oscillators is quantified by a decrease in the
      phase synchronization index. The experimental results are reproduced in
      simulations which demonstrate that the decrease in the degree of synchronization
      is correlated with the appearance of a small fraction of permanently excited
      beads in BZ populations of high mean frequency and/or large width.

PMID- 17176156
TI  - Combining reactive and configurational-bias Monte Carlo: confinement influence on
      the propene metathesis reaction system in various zeolites.
AB  - In order to efficiently calculate chemical equilibria of large molecules in a
      confined environment the reactive Monte Carlo technique is combined with the
      configurational-bias Monte Carlo approach. To prove that detailed balance is
      fulfilled the acceptance rule for this combination of particular Monte Carlo
      techniques is derived in detail. Notably, by using this derivation all other
      acceptance rules of any Monte Carlo trial moves usually carried out in
      combination with the configurational-bias Monte Carlo approach can be deduced
      from it. As an application of the combination of reactive and configurational
      bias Monte Carlo the influence of different zeolitic confinements (MFI, TON, LTL,
      and FER) on the reaction equilibrium and the selectivity of the propene
      metathesis reaction system was investigated. Compared to the bulk phase the
      conversion is increased significantly. The authors study this reaction system in
      the temperature range between 300 and 600 K, and the pressure range from 1 to 7
      bars. In contrast to the bulk phase, pressure and temperature have a strong
      influence on the composition of the reaction mixture in confinement. At low
      pressures and temperatures both conversion and selectivity are highest.
      Furthermore, the equilibrium composition is strongly dependent on the type of
      zeolite. This demonstrates the important role of the host structure in catalytic
      systems.

PMID- 17176157
TI  - Ultrafast fluorescence resonance energy transfer in a reverse micelle: excitation
      wavelength dependence.
AB  - Fluorescence resonance energy transfer (FRET) from coumarin 480 (C480) to
      fluorescein 548 (F548) in a sodium dioctyl sulfosuccinate (AOT) reverse micelle
      is studied by picosecond and femtosecond emission spectroscopy. In bulk water, at
      the low concentration of the donor (C480) and the acceptor (F548), no FRET is
      observed. However, when the donor (C480) and the acceptor (F548) are confined in
      a AOT reverse micelle very fast FRET is observed. The time constants of FRET were
      obtained from the rise time of the emission of the acceptor (F548). In a AOT
      microemulsion, FRET is found to occur in multiple time scales--3, 200, and 2700
      ps. The 3 ps component is assigned to FRET in the water pool of the reverse
      micelle with a donor-acceptor distance, 16 A. The 200 ps component corresponds to
      a donor-acceptor distance of 30 A and is ascribed to the negatively charged
      acceptor inside the water pool and the neutral donor inside the alkyl chains of
      AOT. The very long 2700 ps component may arise due to FRET from a donor outside
      the micelle to an acceptor inside the water pool and also from diffusion of the
      donor from bulk heptane to the reverse micelle. With increase in the excitation
      wavelength from 375 to 405 nm the relative contribution of the FRET due to C480
      in the AOT reverse micelle (the 3 and 200 ps components) increases.

PMID- 17176158
TI  - Correction of apparent finite size effects in the area per lipid of lipid
      membranes simulations.
AB  - Molecular dynamics simulations of lipids bilayers have reported that the average
      area per lipid increases with the size of the simulated unit cell under constant
      temperature, pressure, and number of molecules. Here we show that the cause of
      this finite size effect are artifacts associated with the heat bath coupling.
      This can be corrected by coupling individually each degree of freedom to the heat
      bath, instead of coupling globally the system. We present the results of the
      investigation on three aspects of molecular dynamics simulations and their effect
      on the computed average area per lipid: (I) the accuracy in the computation of
      electrostatic interactions, the energy, and the virial, (II) long range Lennard
      Jones interactions for systems with symmetry in one plane, and (III)
      thermodynamic baths. We show that the average area per lipid remains constant for
      simulations of systems containing 32, 64, and 256 lipids.

PMID- 17176159
TI  - Modeling the release of nanoparticles from mobile microcapsules.
AB  - The authors present a novel computational approach to simulate both the release
      of nanoparticles from a microcapsule, which is moving through a microchannel, and
      the adsorption of the released particles onto the channel walls. By integrating
      the lattice spring model for the micromechanics of elastic solids and the lattice
      Boltzmann model for fluid dynamics, they simulate the relevant fluid-structure
      interactions in the system. In particular, they capture the dynamic interactions
      among the capsule's elastic shell, the encapsulated fluid, and the external, host
      solution. The nanoparticles are treated as "tracer particles" and their motion is
      modeled via a Brownian dynamics simulation. An imposed pressure gradient drives
      the capsule to move along an adhesive substrate and the particles are released
      from the surface of this mobile capsule. The authors determine how the elasticity
      of the capsule, the strength of the capsule-surface adhesion and the diffusion
      coefficient of the nanoparticles affect the relative amount of particles that are
      adsorbed onto the substrate. In addition to showing that the compliant nature of
      the capsule can significantly affect the nanoparticle deposition, they isolate a
      range of parameters for maximizing the adsorbed amount. The findings yield
      guidelines for optimizing the efficiency of microcapsule carriers in the targeted
      delivery of nanoparticles.

PMID- 17176160
TI  - Aggregation-governed oriented growth of inorganic crystals at an organic
      template.
AB  - X-ray studies performed during the growth of CdCO(3) and MnCO(3) crystals from
      supersaturated aqueous solutions, at fatty acid monolayer templates, reveal that
      the nucleates are nearly three-dimensional powders below a threshold
      supersaturation. However, at higher supersaturations, the crystals are
      preferentially oriented with the {0 1 2} direction vertical. Scanning electron
      microscope images of samples transferred to substrates show discrete crystals at
      low concentrations, while at higher concentrations the crystals self-aggregate to
      form linear chains and sheets. The authors speculate that preferential alignment
      at the organic-inorganic interface is enhanced as a consequence of oriented
      aggregation of crystals. The role of monolayer-ion interactions in governing the
      morphologies and the resulting orientation of the inorganic nucleate is
      discussed.

PMID- 17176161
TI  - Association-dissociation equilibrium of loop structures in single-chain folding
      into a toroidal condensate.
AB  - Recently, it has been revealed that a semiflexible polyelectrolyte chain can form
      a partially folded conformation stably as a result of an electrostatic
      interaction. Interestingly, there are cases where the appearance of this
      structure requires a high-salt condition of a solution. In order to solve this
      problem, we consider the double equilibrium of the formation of loops and their
      aggregation on a single-chain polymer. First, an aggregate with a typical surface
      energy is examined as a test case. The basic nature of the folding transition is
      discussed with regard to the chemical potential of loop structures. Next, we
      consider a charged aggregate for which the interior is completely neutralized by
      counter ions. In this model, a partially folded chain appears with a high-salt
      condition. Based on this model, screened interactions between surface charges and
      a toroidal shape of a folded structure are considered essential factors bihind
      this phenomenon.

PMID- 17176162
TI  - Self-trapping of the N-H vibrational mode in alpha-helical polypeptides.
AB  - Recent calculations on the formation of self-trapped amide group vibrational
      states in alpha-helical polypeptides [J. Chem. Phys. 124, 134907 (2006)] are
      extended to the amide N-H normal mode vibrations. First, the adiabatic N-H
      vibrational single- and two-exciton states are examined by treating the
      longitudinal chain coordinates as parameters. Then, in using the
      multiconfiguration time-dependent Hartree method coupled exciton-chain
      vibrational quantum dynamics are accounted for. Based on the respective exciton
      chain vibrational wave function propagation the infrared transient absorption
      related to a sequential pump-probe experiment is calculated. The modulation of
      local amide vibrational energies by the longitudinal chain coordinates is found
      to have a pronounced effect on the broadening of absorption lines. Moreover, the
      ultrafast exciton transfer in the system is studied in order to characterize the
      dynamics of the self-trapped single-exciton states on a time scale below 10 ps.

PMID- 17176164
TI  - Self-diffusion constants in silicon: ab initio calculations in combination with
      classical rate theory.

PMID- 17176163
TI  - Analytical model for studying how environmental factors influence protein
      conformational stability in solution.
AB  - We introduce an analytical modeling strategy for probing the conformational
      stability of globular proteins in aqueous solution. In this approach, the
      intrinsic (i.e., infinite dilution) thermodynamic stability and coarse structural
      properties of the proteins, as well as the effective protein-protein
      interactions, derive from a heteropolymer collapse theory that incorporates
      predicted temperature- and pressure-dependent hydrophobic interactions. Protein
      concentration effects are estimated by integrating this information into a
      molecular thermodynamic model, which is an ad hoc generalization of the exact
      equilibrium theory of a one-dimensional binary mixture of square-well particles
      that interconvert through an isomerization (i.e., folding) reaction. The end
      result is an analytical multiscale modeling approach which, although still
      schematic, can predict that folded proteins exhibit a closed-loop region of
      stability in the pressure-temperature plane and that protein concentration has a
      nonmonotonic effect on protein stability, results consistent with qualitative
      trends observed in both experiments of protein solutions and simulations of
      coarse-grained protein models.

PMID- 17176166
TI  - Ancient medicine, modern use: Withania somnifera and its potential role in
      integrative oncology.
AB  - Withania somnifera Dunal, commonly known as ashwagandha, has been used for
      centuries in Ayurvedic medicine to increase longevity and vitality. Western
      research supports its polypharmaceutical use, confirming antioxidant, anti
      inflammatory, immune-modulating, and antistress properties in the whole plant
      extract and several separate constituents. This article reviews the literature
      pertaining to Withania somnifera and its botanical constituents as antitumor
      agents and in conjunction with radiation and chemotherapy treatment. Following a
      search of MEDLINE and EBSCO databases, it can be concluded that Withania
      somnifera reduces tumor cell proliferation while increasing overall animal
      survival time. Furthermore, it has been shown to enhance the effectiveness of
      radiation therapy while potentially mitigating undesirable side effects. Withania
      somnifera also reduces the side effects of chemotherapeutic agents
      cyclophosphamide and paclitaxel without interfering with the tumor-reducing
      actions of the drugs. These effects have been demonstrated in vitro on human
      cancer cell lines, and in vivo on animal subjects, but there have been no human
      trials to date. Given its broad spectrum of cytotoxic and tumor-sensitizing
      actions, Withania somnifera presents itself as a novel complementary therapy for
      integrative oncology care.

PMID- 17176167
TI  - Body temperature variability (Part 1): a review of the history of body
      temperature and its variability due to site selection, biological rhythms,
      fitness, and aging.
AB  - Body temperature is a complex, non-linear data point, subject to many sources of
      internal and external variation. While these sources of variation significantly
      complicate interpretation of temperature data, disregarding knowledge in favor of
      oversimplifying complex issues would represent a significant departure from
      practicing evidence-based medicine. Part 1 of this review outlines the historical
      work of Wunderlich on temperature and the origins of the concept that a healthy
      normal temperature is 98.6 degrees F (37.0 degrees C). Wunderlich's findings and
      methodology are reviewed and his results are contrasted with findings from modern
      clinical thermometry. Endogenous sources of temperature variability, including
      variations caused by site of measurement, circadian, menstrual, and annual
      biological rhythms, fitness, and aging are discussed. Part 2 will review the
      effects of exogenous masking agents - external factors in the environment, diet,
      or lifestyle that can influence body temperature, as well as temperature findings
      in disease states.

PMID- 17176169
TI  - 5-methyltetrahydrofolate. Monograph.

PMID- 17176168
TI  - Peripheral neuropathy: pathogenic mechanisms and alternative therapies.
AB  - Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy,
      human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient
      deficiencies, heavy metal toxicity, and other etiologies, results in significant
      morbidity. Conventional pain medications primarily mask symptoms and have
      significant side effects and addiction profiles. However, a widening body of
      research indicates alternative medicine may offer significant benefit to this
      patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine,
      methylcobalamin, and topical capsaicin are among the most well-researched
      alternative options for the treatment of PN. Other potential nutrient or
      botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin,
      myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N
      acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of
      physical medicine, acupuncture, magnetic therapy, and yoga have been found to
      provide benefit. New cutting-edge conventional therapies, including dual-action
      peptides, may also hold promise.

PMID- 17176170
TI  - Chondroitin sulfates. Monograph.

PMID- 17176171
TI  - Does solitary substance use increase adolescents' risk for poor psychosocial and
      behavioral outcomes? A 9-year longitudinal study comparing solitary and social
      users.
AB  - This longitudinal study compared Grade 8 solitary cigarette smokers (n = 541),
      drinkers (n = 577), and marijuana users (n = 148) with adolescents who restricted
      their use of these substances to social settings (ns = 562, 1,426, and 388,
      respectively) on adolescent functioning and young adult outcomes. In Grade 8,
      solitary users held more positive beliefs about the consequences of substance
      use, earned poorer grades, engaged in more deviant behavior, and devoted less
      time to school and more time to social activities. By age 23, these solitary
      users had lower educational attainment, poorer self-rated health, and greater
      substance use problems. Results indicate the importance of better understanding
      and addressing the needs of this understudied group of high-risk youth.

PMID- 17176172
TI  - Comparison of longitudinal phenotypes based on number and timing of assessments:
      a systematic comparison of trajectory approaches II.
AB  - The popularity of trajectory-based research to characterize developmental courses
      of alcohol (and other drug) involvement is growing rapidly. Given the increasing
      use of these methods, there is a need to identify methodological factors that
      affect course shape and prevalence. Using growth mixture models, the authors
      characterized the developmental course of 2 indices of alcohol involvement,
      alcohol use disorder and frequency of heavy drinking, with a prospective sample
      of 489 young adults (Year 1 age = 18.52; 55% female; 51% with family history of
      alcoholism) assessed 6 times over 11 years. Then, the authors explored the extent
      to which trajectory models that eliminated an assessment (at the beginning,
      middle, or end of the study interval) were similar to the full 6-wave model.
      Although classifications showed relatively high concordance, trajectory shape and
      predicted prevalences varied. Misclassification was associated with
      methodological factors such as probability of class membership and missing data.
      Findings suggest that researchers thoughtfully consider the nature of the
      phenomena being studied and the developmental period of interest when designing
      prospective studies.

PMID- 17176173
TI  - Patterns and importance of self-other differences in college drinking norms.
AB  - College students overestimate other students' drinking behavior (descriptive
      norms) and attitudes (injunctive norms). This study explored the effects of
      demographics, norm type, and reference group on the magnitude of self- other
      differences (SODs). Participants (N = 1,611; 64% women) completed surveys
      assessing demographics, drinking patterns, and perceived norms. A subset of 122
      students provided consumption data 1 month later to test predictors of changes in
      drinking. Overall, women and non-Greeks (Greek = member of fraternity or
      sorority) reported larger SODs for both norm types compared with men and Greeks.
      Heavier drinkers reported smaller SODs. Gender x Reference Group interactions
      revealed that women had larger SODs for reference groups increasingly distal to
      them; for men, the largest SODs occur for close friends versus more distal
      groups. Larger SODs for descriptive norms predicted increases in drinking,
      consistent with social norms theory.

PMID- 17176174
TI  - Childhood victimization and illicit drug use in middle adulthood.
AB  - Using a prospective cohort design, the authors examined in this study whether
      childhood victimization increases the risk for illicit drug use and related
      problems in middle adulthood. Court-documented cases of childhood physical and
      sexual abuse and neglect and matched controls (N = 892) were first assessed as
      young adults (mean age = 29 years) during 1989-1995 and again in middle adulthood
      (mean age = 40 years) during 2000-2002. In middle adulthood, abused and neglected
      individuals were about 1.5 times more likely than controls to report using any
      illicit drug (in particular, marijuana) during the past year and reported use of
      a greater number of illicit drugs and more substance-use-related problems
      compared with controls. The current results reveal the long-term impact of
      childhood victimization on drug use in middle adulthood. These new results
      reinforce the need for targeted interventions with abused and neglected children,
      adolescents, and adults, and particularly for women.

PMID- 17176175
TI  - Pubertal maturation and early substance use risks among African American
      children.
AB  - Using 2 waves of longitudinal data collected from approximately 870 African
      American adolescents, this study examined (a) changes in early risk factors for
      substance use during transition to early adolescence, including perceived
      prototypes of substance-using peers, willingness and intention to use substances,
      number of substance-using peers, and youths' own actual substance use; (b) the
      relationship between pubertal timing and these substance use risks; and (c) the
      interaction between pubertal timing and peer substance use in predicting the
      risks. Results showed that, first, risks for substance use increased,
      particularly among girls, during the transition to early adolescence. Children's
      prototypic images of substance users became increasingly favorable during this
      transitional period; a greater number of them were willing and intended to use
      substances during the transition to early adolescence; and an increased number of
      early adolescents and their friends began to use substances. Second, these
      changes were significantly more likely to occur among early maturing girls.
      Third, early physical maturation interacted with peer substance use to affect
      these changes.

PMID- 17176176
TI  - Personality and substance dependence symptoms: modeling substance-specific
      traits.
AB  - Personality traits related to neuroticism and disinhibition have been
      consistently associated with substance use disorders (SUDs). It is unclear,
      however, whether different personality traits predict distinct forms of substance
      dependence. Additionally, it is unclear whether personality traits continue to
      predict alcohol, drug, and tobacco dependence after controlling for comorbid
      antisociality and other SUDs. The current study addresses these questions by
      characterizing relations between personality traits and substance dependence
      symptoms in a longitudinal sample of 3,720 college students. Results revealed
      that antisociality and certain core personality traits predicted multiple types
      of substance pathology. In addition, several personality traits were
      differentially associated with alcohol, drug, and tobacco symptomatology.

PMID- 17176177
TI  - Trauma-focused imaginal exposure for individuals with comorbid posttraumatic
      stress disorder and alcohol dependence: revealing mechanisms of alcohol craving
      in a cue reactivity paradigm.
AB  - With a sample (N = 43) of participants meeting current diagnostic criteria for
      both alcohol dependence and posttraumatic stress disorder (PTSD), the authors
      tested the hypothesis that alcohol craving elicited by a trauma cue might be
      attenuated if trauma-elicited negative emotion were reduced following trauma
      focused imaginal exposure. In a laboratory-based experiment, participants were
      randomly assigned to either trauma-focused imaginal exposure or imagery-based
      relaxation. A cue reactivity paradigm was used to assess alcohol craving prior
      to, and after completion of, the 6 clinical sessions. Attrition was high but did
      not differ between experimental conditions. For study completers, PTSD symptoms
      decreased in the exposure condition but not in the relaxation condition. Alcohol
      craving and distress elicited by trauma images decreased in the exposure
      condition but did not change in the relaxation condition. Results support the
      hypothesis that negative emotion is a mechanism of alcohol craving.

PMID- 17176178
TI  - Implicit and explicit measures of alcohol and smoking cognitions.
AB  - The present study tested convergent, discriminant, and incremental validity of
      implicit and explicit measures of alcohol and smoking cognitions. College-aged
      participants (n = 264) completed questionnaire measures of alcohol and smoking
      expectancies and behavior. Participants also completed the Implicit Association
      Test (IAT; Greenwald, McGhee, & Schwartz, 1998) for alcohol and smoking on two
      occasions, approximately 1 month apart. Psychometric qualities of these IATs were
      evaluated. Modest associations were found between implicit and explicit measures
      for the same substance. Both implicit and explicit measures had unique
      associations with use. Discriminant validity was stronger for alcohol measures
      than for smoking measures. These results support the utility of the IAT as a
      technique for assessing implicit associations about alcohol and smoking. They
      also provide some evidence that smoking motivations may make unique contributions
      to alcohol use.

PMID- 17176179
TI  - Use of a multiple-choice procedure with college student drinkers.
AB  - The Multiple-Choice Procedure (MCP) was developed to investigate the relationship
      between drug preferences and alternative reinforcers. The current studies were
      designed to validate survey and laboratory versions of the MCP with college
      student drinkers. In Study 1, 320 undergraduates with a recent history of alcohol
      consumption used a survey version of the MCP to make 120 discrete hypothetical
      choices between two amounts of alcohol and escalating amounts of money delivered
      immediately or after a 1-week delay. In Study 2, 21 undergraduates completed a
      laboratory version of the MCP to make 120 discrete choices involving real alcohol
      and monetary payments. Responses to both versions of the MCP were related to
      measures of alcohol use and varied as a function of delay associated with the
      money choice. Responses to the survey version of the MCP also varied as a
      function of the amount of alcohol hypothetically available. The results of the 2
      studies are consistent with a behavioral choice perspective of alcohol use, which
      focuses on preferences in the context of competing alternative reinforcers.

PMID- 17176180
TI  - The development and initial evaluation of the survey of readiness for alcoholics
      anonymous participation.
AB  - This article presents 5 studies related to the development and initial evaluation
      of the Survey of Readiness for Alcoholics Anonymous Participation (SYRAAP). The
      SYRAAP is a brief, multidimensional, self-administered instrument that assesses
      beliefs associated with Alcoholics Anonymous (AA) participation. Study 1
      generated 239 candidate items for potential inclusion in the instrument. Study 2
      assessed the content validity of these items according to 3 criteria and
      identified a subset of 60 with the highest values on the criteria for further
      consideration. Study 3 produced a shorter version of the SYRAAP and evaluated its
      structure, internal reliability, and validity. Study 4 reevaluated the structure
      and internal reliability of the SYRAAP and yielded findings that were generally
      consistent with those from Study 3. Study 5 established stability reliability for
      the instrument. The collective findings indicated the SYRAAP can reliably and
      validly assess individual-level beliefs associated with AA participation. The
      potential use of the SYRAAP for researchers and clinicians, along with
      limitations of the work presented here, are discussed.

PMID- 17176182
TI  - Family history of alcoholism and the stability of personality in young adulthood.
AB  - The authors examined the magnitude and durability of personality differences
      related to family history of alcoholism (FH) and the development of alcohol use
      disorders (AUDs) in late adolescence and early adulthood. Data were taken from a
      longitudinal sample (N = 487; approximately half FH-positive [+]) who completed
      the Eysenck Personality Questionnaire (H. J. Eysenck & S. B. G. Eysenck, 1975) at
      3 points spanning 11 years (participants were 18 years old at baseline).
      Hierarchical linear analyses showed that FH+ participants had higher levels of
      neuroticism and psychoticism over the study period, independent of AUD. Despite
      relatively large mean decreases in neuroticism (as well as extraversion), the
      magnitude of the between-groups differences found at age 18 were maintained over
      the next decade. These changes thus reflect stable underlying differences in
      personality and not artifacts of higher rates of AUDs in FH+ individuals,
      recently living in an alcoholic home, vulnerability to the developmental
      challenge of leaving home, and/or a developmental lag.

PMID- 17176181
TI  - Development and initial validation of an instrument to measure perceived coercion
      to enter treatment for substance abuse.
AB  - The present study involved 3 phases that led to the development and initial
      validation of the Perceived Coercion Questionnaire (PCQ), a scale that
      researchers use to measure perceptions of coercion of drug and alcohol users to
      enter drug and alcohol treatment. In Phase 1, the authors used focus groups to
      generate 48 pilot items. In Phase 2, the items were administered to a sample of
      158 drug and alcohol users who were in residential treatment within a therapeutic
      community setting. Item and exploratory factor analyses reduced the number of
      items to 32, which represented 6 homogeneous and internally reliable subscales.
      In Phase 3, the PCQ was administered to a second sample of 362 drug and alcohol
      users. Confirmatory factor analysis led to a final scale of 30 items across 6
      subscales that demonstrated sound consistency and validity. Implications for
      research and practice are highlighted.

PMID- 17176183
TI  - Psychostimulant users are sensitive to the stimulant properties of alcohol as
      indexed by alcohol-induced cardiac reactivity.
AB  - One indicator of increased sensitivity to alcohol-induced reward is a heightened
      heart rate (HR) increase following alcohol intoxication, a characteristic
      associated with increased alcohol-induced dopamine (DA) release. The goal of this
      study was to determine whether users of drugs known to induce DA release have
      higher HR increases after alcohol intoxication than never users have. Sixty-four
      men with known drug-use histories participated in an alcohol challenge in which
      HR was measured. Stimulant users had significantly higher ethanol-induced HR
      increases than never users had, although use of marijuana or hallucinogens was
      not associated with this marker. Stimulant users obtained superior Sensitivity to
      Reward scores (R. Torrubia, C. Avila, J. Molto, & X. Caseras, 2001) compared with
      never users. Stimulant drug users may be more sensitive to the stimulating
      properties of alcohol, and this appears to be mediated by superior activity in
      the Behavioral Approach System (J. A. Gray, 1991).

PMID- 17176184
TI  - Smoking cues in a virtual world provoke craving in cigarette smokers.
AB  - Twenty smoking-deprived cigarette smokers participated in a study to test the
      ability of smoking cues within a virtual world to provoke self-reported craving
      to smoke. Participants were exposed to 2 virtual-reality simulations displayed on
      a computer monitor: a control environment not containing any intentional smoking
      stimuli and a cue-exposure environment containing smoking stimuli. At various
      points, participants rated their urge to smoke on a scale of 0-100. Results
      indicated that baseline urge ratings were equivalent in both conditions, but the
      maximum increase in urge ratings was significantly higher in the cue-exposure
      environment than in the control environment. This is comparable to what in vivo
      studies have reported, but with the advantage of simulating more naturalistic and
      complex settings in a controlled environment.

PMID- 17176185
TI  - Attentional bias for smoking and affective stimuli: a Stroop task study.
AB  - Prior research has demonstrated attentional biases to smoking-related cues among
      smokers, and several lines of research suggest strong ties between smoking and
      negative affect. The authors tested attentional biases to both smoking and
      affective cues in 27 smokers using an emotional Stroop paradigm, and examined the
      relationship between these forms of attentional bias. Findings indicated
      significant attentional biases to smoking-related and negative-affect words, but
      not positive-affect words. In addition, there was a significant correlation
      between the degree of attentional bias to smoking and negative-affect words.
      These data provide evidence of a close association between smoking-related and
      affective cue processing from a cognitive perspective. Potential theoretical and
      clinical implications for these findings are discussed.

PMID- 17176186
TI  - Drug abuse risk and protective factors among black urban adolescent girls: a
      group-randomized trial of computer-delivered mother-daughter intervention.
AB  - A group-randomized design tested a mother-daughter intervention in which
      researchers aimed to increase protective factors in a community sample of Black
      urban adolescent girls. Girls and their mothers at 2 community agencies were
      pretested and, by agency, were randomized to either an intervention arm or a
      control arm. Intervention arm girls and their mothers received a program for
      improving mother- daughter rapport. Posttest data collected 3 weeks after program
      delivery revealed that intervention arm mothers and daughters improved more than
      did control arm mothers and daughters on measures of communication and closeness.
      At 3-month follow-up, intervention arm mothers, relative to control arm mothers,
      continued to report better communication with and closeness to their daughters.
      Girls and mothers in the intervention arm rated the computer program favorably on
      parameters of enjoyment, comfort, relevance, usefulness of information,
      improvements to their relationship with one another, and whether they would
      recommend the computer program to friends.

PMID- 17176187
TI  - Treatment techniques and outcomes in multidimensional family therapy for
      adolescent behavior problems.
AB  - The link between treatment techniques and long-term treatment outcome was
      examined in an empirically supported family-based treatment for adolescent drug
      abuse. Observational ratings of therapist interventions were used to predict
      outcomes at 6 and 12 months posttreatment for 63 families receiving
      multidimensional family therapy. Greater use of in-session family-focused
      techniques predicted reduction in internalizing symptoms and improvement in
      family cohesion. Greater use of family-focused techniques also predicted reduced
      externalizing symptoms and family conflict, but only when adolescent focus was
      also high. In addition, greater use of adolescent-focused techniques predicted
      improvement in family cohesion and family conflict. Results suggest that both
      individual and multiperson interventions can exert an influential role in family
      based therapy for clinically referred adolescents.

PMID- 17176188
TI  - Domestic violence, maternal parenting, maternal mental health, and infant
      externalizing behavior.
AB  - This study examined whether maternal functioning mediated the relationship
      between domestic violence (DV) and infant externalizing behavior. Participants
      were 203 mother-infant dyads. Support was found for a partially mediated model in
      which maternal functioning mediated the relationship between current DV and
      infant externalizing behaviors. Past DV was directly associated with infants'
      externalizing behavior. Results suggest the need for early intervention and
      prevention efforts for families living with DV.

PMID- 17176189
TI  - Pre-engagement cohabitation and gender asymmetry in marital commitment.
AB  - The authors longitudinally examined couples' (N = 197) dedication (interpersonal
      commitment) levels on the basis of their premarital cohabitation history.
      Findings suggested that men who cohabited with their spouse before engagement
      were less dedicated than men who cohabited only after engagement or not at all
      before marriage. Furthermore, these husbands were less dedicated to their wives
      than their wives were to them. Hierarchical linear modeling showed that such
      asymmetries were apparent before marriage and through the early years of
      marriage. Relationship adjustment and religiousness were related to dedication
      but did not account for the findings. The authors suggest that couples
      considering cohabitation before engagement could benefit from discussions about
      commitment and expectations about marriage.

PMID- 17176190
TI  - The marriage moments program for couples transitioning to parenthood: divergent
      conclusions from formative and outcome evaluation data.
AB  - This article presents the results of a pilot study of the Marriage Moments
      program, designed to prevent relationship deterioration during the 1st year of
      parenthood. The self-guided, low-intensity program emphasizes strengthening
      marital virtues and partnership during this time of significant personal and
      family transition. One hundred fifty-five married couples participated in a
      randomized clinical trial with 2 psychoeducational treatment groups (a self
      guided group and an instructor-encouraged group) and a comparable control group.
      Despite positive formative evaluation results from program participants,
      hierarchical linear modeling analyses failed to find significant Group x Time
      differences on spouses' reports of marital virtues and a set of relational
      outcome measures. This failure reinforces the need for psychoeducators to invest
      in outcome evaluation research before claiming program success.

PMID- 17176191
TI  - Cultural socialization in families with internationally adopted children.
AB  - Cultural socialization attitudes, beliefs, and parenting behaviors were examined
      in families with internationally adopted children. The authors hypothesized that
      parents with lower color-blind racial attitudes would be more likely to engage in
      enculturation and racialization parenting behaviors because they hold stronger
      beliefs in the value and importance of cultural socialization. Using data from
      the Minnesota International Adoption Project, the results support this mediation
      model of cultural socialization. Individual variations in cultural socialization
      also are discussed in terms of child development and shifting adoption attitudes
      and practices.

PMID- 17176192
TI  - Examining the correlates of psychological aggression among a community sample of
      couples.
AB  - In this study, the authors examined the correlates of psychological aggression
      victimization and perpetration among a community sample of 145 heterosexual
      couples. For both women and men, psychological aggression victimization was
      associated with greater psychological distress, anxiety, and physical health
      symptoms beyond the effects of physical aggression. Psychological aggression
      victimization was also uniquely associated with higher levels of depression for
      women. Trait anger and poor relationship adjustment were the strongest correlates
      of psychological aggression perpetration across genders. Childhood father-to
      child and father-to-mother aggressions were associated with psychological
      aggression perpetration for men only, suggesting possible distinct etiologies
      across genders. These data highlight the importance of the further development of
      models for psychological aggression in both women and men.

PMID- 17176193
TI  - Differential impact of fathers' authoritarian parenting on early adolescent
      adjustment in conservative protestant versus other families.
AB  - The purpose of the study was to determine whether well-established associations
      between authoritarian parenting and adolescent adjustment pertain to conservative
      Protestant (CP) families. Structural equation modeling was used to test paths
      from biological fathers' authoritarian parenting to adolescent adjustment in 65
      CP versus 170 comparison families in the Nonshared Environment and Adolescent
      Development Study (NEAD; D. Reiss et al., 1994). The hypothesis that adolescents
      in CP families would be less harmed by authoritarian parenting than would
      adolescents in control families was partially supported: Authoritarian parenting
      directly predicted greater externalizing and internalizing for adolescents in
      control families but not for adolescents in CP families. In contrast, parents'
      religious affiliation failed to moderate the negative associations between
      authoritarian parenting and positive adjustment. Understanding family processes
      specific to the CP subculture is important for helping these families raise
      competent children.

PMID- 17176194
TI  - Parenting and community background and variation in women's life-history
      development.
AB  - For a community sample of 623 low-income women (mean age = 26.9 years), the
      authors use life-history theory to explore relations between parenting and
      community background and timing of reproductive development and sexual behaviors.
      Among other patterns, reported levels of paternal involvement during childhood
      were related to delayed menarche and ages at 1st sexual intercourse and 1st
      childbirth. The relation between parental investment and women's reproductive
      delay varied with estimates of wealth in the community in which the participants
      grew up. The results suggest that parents increased their investment as the level
      of community wealth increased, and in ways that likely facilitated women's
      ability to compete for social status in adulthood. Implications for future
      research on the relation between parenting and child outcomes are discussed.

PMID- 17176195
TI  - Examining the origins of gender differences in marital quality: a behavior
      genetic analysis.
AB  - Numerous researchers have examined gender differences in marital quality, with
      mixed results. In this study, the authors further this investigation by looking
      for genetic and environmental sources of variation in marital quality. The 1st
      aim of the study was to replicate previous findings of genetic and nonshared
      environmental influences on marital quality. The 2nd was to explore the etiology
      of gender differences in marital quality. The Virginia Adult Twin Study of
      Psychiatric and Substance Use Disorders sample of twin men and twin women was
      used. Genetic and nonshared environmental factors were again found to influence
      marital quality. Findings also suggest small differences between men and women in
      the levels of genetic and environmental influence on variance in marital quality.
      The men's reports of marital warmth and conflict were influenced by the same
      genetic factors, but women's reports of marital warmth and conflict were
      influenced by different genetic factors. Results are discussed in the context of
      previous research on social support and implications for future studies of the
      etiology of marital quality.

PMID- 17176196
TI  - Microregulatory patterns of family interactions: cultural pathways to toddlers'
      self-regulation.
AB  - Pathways to children's self-regulation were examined in 2 cultures representing
      individualistic and collectivistic orientations. Family interactions were
      observed in 100 Israeli and 62 Palestinian couples and their firstborn child at 5
      months and in a problem-solving task at 33 months. Patterns of gaze, affect,
      proximity, touch, and parental teaching strategies were coded. Child self
      regulation was observed at child care locations. Among Israeli families,
      interactions involved face-to-face exchange, social gaze, object focus, and
      active touch in infancy and indirect parental assistance to toddlers. Among
      Palestinian families, interactions consisted of continuous contact, neutral
      affect, reduced negative emotionality, and concrete assistance. Levels of self
      regulation were comparable and were predicted by culture-specific patterns.
      Social gaze, touch, and indirect teaching were found to predict self-regulation
      among Israeli toddlers; contact and concrete assistance were predictors among
      Palestinians. Discussion considers the ways early relational patterns mirror
      cultural philosophies on the self and differentially support self-regulation at
      the transition from family to the larger social context.

PMID- 17176197
TI  - Relationship separation for young, at-risk couples: prediction from dyadic
      aggression.
AB  - Dyadic physical aggression in the relationships of 158 young, at-risk couples was
      examined as a predictor of relationship separation over the course of 6 years. A
      high prevalence of physical aggression and a high rate of separation were found,
      with 80% of couples engaging in physical aggression (as reported by either
      partner or as observed) and 62% separating over time. As predicted, physical
      aggression significantly increased the likelihood of relationship dissolution,
      even after accounting for psychological aggression, prior relationship
      satisfaction, and relationship contextual factors (length of relationship,
      relationship type, and children in the household). Of the contextual factors,
      relationship type was predictive of relationship dissolution: Married couples
      were least likely to dissolve their relationships compared with cohabiting and
      dating couples.

PMID- 17176198
TI  - Assessing adult adjustment to relationship separation: the Psychological
      Adjustment to Separation Test (PAST).
AB  - Relationship separation is associated with substantial adult adjustment problems.
      The Psychological Adjustment to Separation Test (PAST) was developed as a self
      report measure of 3 key dimensions of separation adjustment problems: lonely
      negativity, ex-partner attachment and coparenting conflict. Two independent
      samples (n = 219 and n = 169, respectively) of recently separated adults, 60% of
      whom had children, completed the PAST and other measures of general adjustment.
      Exploratory and confirmatory factor analyses demonstrated a replicable 3-factor
      structure, with each factor showing satisfactory test-retest and internal
      reliability and good convergent and discriminant validity. The PAST meets initial
      criteria for a potentially useful new measure of adult separation adjustment.

PMID- 17176199
TI  - Maternal variations in stress reactivity: implications for harsh parenting
      practices with very young children.
AB  - Although a wide array of variables has been found to predict harsh parenting,
      less is known about the linkages among these variables. It is suggested here that
      stress reactivity, as reflected in cortisol changes, is an important mediating
      variable. In a high-risk population, mothers (N = 60) with low perceived power
      (as measured by the Parent Attribution Test; D. B. Bugental, J. B. Blue, & M.
      Cruzcosa, 1989), were highly reactive to infants and toddlers with a difficult
      temperament pattern. In response to such children, they (a) manifested high
      cortisol reactivity and (b) reported greater use of harsh control practices
      (e.g., spanking). Cortisol reactivity was found to mediate the observed
      relationship between the predictor variable (the interaction between maternal
      "powerlessness" and the child's temperament) and parental harshness. These
      findings have clinical implications for the ways in which parental empowerment
      (via early interventions) can serve to reduce stress and thus the negative
      outcomes at-risk children may experience.

PMID- 17176200
TI  - Depressive vulnerability in parents and their 5-year-old child's temperament: a
      family system perspective.
AB  - The actor-partner interdependence model was used to test whether one parent's
      depressive vulnerability (self-criticism and dependency) was associated with the
      same parent's own (an intraparental association) and the other parent's (a cross
      parental association) ratings of their 5-year-old child's temperament (536
      parents, 268 dyads). The more vulnerable the parents were, the more the children
      showed negative affectivity and lack of effortful control. Significant
      interactions with the parent's gender and between the spouses' depressive
      vulnerabilities were found, highlighting the fact that child outcomes are
      dependent on family processes. All associations were independent of maternal and
      paternal depressive symptoms. The influence of personality-based depressive
      traits on child temperamental outcomes and effective parenting is discussed with
      reference to between-dyad family dynamics.

PMID- 17176201
TI  - Agreement about acts of aggression in marriage.
AB  - Psychological and Physical Aggression scales met internal consistency and
      agreement standards on the Revised Conflict Tactics Scales (CTS2) in a randomly
      recruited sample of 453 married community couples with children. Moreover,
      partners agreed on the extent of psychological and physical aggression as much or
      more than they did on CTS2 Negotiation scale and positive behaviors assessed on
      the Dyadic Adjustment Scale. On the other hand, the CTS2 Sexual Coercion and
      Injury scales had much lower internal consistencies as measured by Cronbach's
      alpha, and agreement was generally very low. Men and women reported less abusive
      behavior and consequent injury than partners reported about them. Correction
      factors were provided for prevalence estimates of abusive behavior and injury
      when only perpetrator reports were available.

PMID- 17176202
TI  - Associations between family cohesion and adolescent siblings' externalizing
      behavior.
AB  - This study asked whether family cohesion, a measure of whole family functioning,
      was associated with adolescent siblings' externalizing problems, controlling for
      the quality of each sibling's relationship with his or her parents. The sample
      included 93 families (mothers, fathers, and 2 adolescent siblings). Family
      cohesion was measured from videotaped observations of parents and 2 of their
      adolescent children discussing family conflict and limit setting. Adolescents
      reported on hostility in their relationships with mothers and fathers, and
      parents rated adolescents' externalizing problems. Results from multilevel
      modeling showed that family cohesion was negatively associated with adolescents'
      externalizing problems, independent of variance explained by hostility in dyadic
      parent-child relationships. Results support family systems theory, suggesting
      that whole family functioning has implications for adolescents' behavioral
      problems beyond those accounted for by dyadic family relationships.

PMID- 17176203
TI  - Ante- and perinatal factors and child characteristics predicting parenting
      experience among formerly infertile couples during the child's first year: a
      controlled study.
AB  - In this prospective controlled study, the authors examined (a) parenting
      experiences among couples with successful assisted reproduction treatment (ART; n
      = 367) and fertile spontaneously conceiving controls (n = 371) and (b) the impact
      of ante- and perinatal factors and child characteristics on parenting
      experiences. The results show that positive mothering experiences increased more
      during the 1st year of parenting and were generally higher among ART mothers than
      control mothers. No differences were found between ART fathers and controls in
      their fathering experience. Unpleasant birth experiences, low birth weight, and
      difficulty soothing the child were associated with high levels of parental stress
      in the control group, but this was not so among the ART parents. Psychosocial
      interventions in maternal care should take into account the various meanings that
      couples give to the history of infertility and conception and ante- and perinatal
      experiences.

PMID- 17176204
TI  - Using random telephone sampling to recruit generalizable samples for family
      violence studies.
AB  - Convenience sampling methods predominate in recruiting for laboratory-based
      studies within clinical and family psychology. The authors used random digit
      dialing (RDD) to determine whether they could feasibly recruit generalizable
      samples for 2 studies (a parenting study and an intimate partner violence study).
      RDD screen response rate was 42-45%; demographics matched those in the 2000 U.S.
      Census, with small- to medium-sized differences on race, age, and income
      variables. RDD respondents who qualified for, but did not participate in, the
      laboratory study of parents showed small differences on income, couple conflicts,
      and corporal punishment. Time and cost are detailed, suggesting that RDD may be a
      feasible, effective method by which to recruit more generalizable samples for in
      laboratory studies of family violence when those studies have sufficient
      resources.

PMID- 17176205
TI  - Daily occupational stressors and marital behavior.
AB  - This study examined daily fluctuations in marital behavior (anger and withdrawal)
      as a function of same-day job stressors, using hierarchical linear modeling
      (HLM). Forty-three couples provided daily diary reports of their workload and
      negative social interactions at work on 5 consecutive days. Within-subject
      analyses demonstrate that husbands and wives reported greater marital anger and
      withdrawal following negative social interactions at work, and wives reported
      greater marital anger and withdrawal following days of heavy workload. Mediation
      analyses provide support for the negative mood spillover hypothesis (e.g.,
      workload no longer predicted wives' marital anger when controlling for negative
      mood). Between-subjects analyses suggest that spouses in high-conflict families
      may be especially vulnerable to the effects of job stressors on marital
      interaction.

PMID- 17176206
TI  - Family functioning in bipolar I disorder.
AB  - In a sample of 62 patients with Bipolar I disorder, the authors used a repeated
      measures longitudinal design to examine whether global family functioning was
      associated with the presence of a concurrent bipolar episode as well as whether
      global family functioning was associated with the presence of manic and
      depressive episodes in the following 3 months. Participants were recruited for a
      randomized clinical trial examining the efficacy of family treatments combined
      with pharmacotherapy for bipolar disorder. Global family functioning was
      repeatedly measured with both clinician-rated and patient-rated assessment
      instruments over the 28-month study period. Results indicated that mood episodes
      were associated with concurrent global family functioning within individuals, but
      global family functioning was not associated with episode status in the
      subsequent 3 months. The repeated measures nature of these results suggests that
      global family functioning and bipolar episodes may fluctuate in concert with each
      other but that global family functioning is not associated with subsequent change
      in episode status.

PMID- 17176207
TI  - Multiple pathways to compliance: mothers' willingness to cooperate and knowledge
      of their children's reactions to discipline.
AB  - Mothers of 59 children with ages from 6 to 9 years were assessed for their
      general willingness to cooperate with their children's desires and their accurate
      predictions of their children's evaluations of different discipline strategies.
      Mothers asked their children to clean up a playroom in their absence, with some
      children protesting and others not protesting. Results showed that maternal
      willing cooperation predicted children's compliance in the absence but not in the
      presence of protest. Conversely, maternal accuracy concerning their children's
      evaluations of discipline facilitated children's compliance in dyads in which
      children expressed initial resistance but not if children indicated no
      opposition. Mothers' responsive reactions to protest mediated between maternal
      accuracy and children's ultimate compliance. Results indicate that specific
      features of parenting facilitate compliance in specific situations.

PMID- 17176208
TI  - Marital relations among former prisoners of war: contribution of posttraumatic
      stress disorder, aggression, and sexual satisfaction.
AB  - In this study, the authors examined the marital adjustment, spousal aggression,
      and sexual satisfaction of prisoners of war (POWs) 3 decades after their release.
      More specifically, the authors examined the extent to which impaired marital
      relations among former POWs are an outcome of their captivity or of the
      posttraumatic stress disorder (PTSD) that some of them developed. The authors
      compared 25 former POWs with PTSD, 85 former POWs without PTSD, and 104 control
      veterans. The findings reveal that the marital problems of former POWs are more
      related to PTSD than to their captivity. PTSD is related to decreased marital
      satisfaction, increased verbal aggression, and heightened sexual dissatisfaction
      among former POWs.

PMID- 17176209
TI  - Rural mental health units--is there a role for a GP?
AB  - INTRODUCTION: Mental illness is a common medical condition which is increasing in
      frequency. In Australia, almost one in five persons have experienced an anxiety,
      depressive or substance abuse disorder in the last 12 months, but less than half
      have sought professional assistance. In rural and remote areas, there is limited
      access to psychiatrists, and the majority of mental health care resides with the
      GP. This study aimed to ascertain the opinions of GPs in rural and remote areas
      of Queensland on the concept of locating a GP within in a mental health unit.
      METHODS: Participants were all general practitioners listed on the databases of
      the Rural Divisions of General Practice covering RRMA 5-7 in Queensland,
      Australia, excluding those who could potentially refer patients to the mental
      health unit where the principal investigator worked. A specially designed
      questionnaire was forwarded to eligible GPs in a series of three mailings.
      RESULTS: In total, 145 GPs returned the questionnaire, giving a 69% response
      rate. The majority of GP respondents believed that there was a significant number
      of patients with mental illness who would benefit from the contribution of a GP,
      and that locating a GP within a mental health unit was a viable option,
      especially for enhancing continuity of care and consequently overall health. The
      majority of respondents said they felt confident in treating mental illness,
      especially those with higher mental health caseloads and those with a
      professional college fellowship. However, there were varying inclinations towards
      working in such a unit, with no definite preferred method of remuneration
      identified. CONCLUSIONS: Rural and remote GPs in Queensland believe there is a
      case for placing a GP within established mental health units, subject to
      addressing logistic and remuneration issues, as they believe this would enhance
      continuity of care and improve overall health for those with mental health
      problems.

PMID- 17176211
TI  - Calcium, vitamin D, and risk reduction of colorectal cancer.

PMID- 17176210
TI  - Immunity to adeno-associated virus-mediated gene transfer in a random-bred canine
      model of Duchenne muscular dystrophy.
AB  - Recombinant adeno-associated virus (rAAV)-mediated gene transfer has shown
      promise for treating diseases in various animal models including the mdx mouse
      model of Duchenne muscular dystrophy (DMD). In many cases, however, preclinical
      studies in inbred mice have not successfully predicted human clinical responses.
      To assess the potential clinical utility of treating human DMD patients by AAV
      mediated gene delivery, we performed a series of direct intramuscular injections
      in random-bred wild-type dogs. AAV serotypes 2 and 6 carrying different promoter
      transgene cassettes were produced as previously described for murine studies and
      administered intramuscularly. The injection sites were biopsied at various time
      points and analyzed for transgene expression and immunohistochemical analysis. In
      contrast to the generally nonimmunogenic nature of these vectors in murine
      studies, both AAV2 and AAV6 vectors elicited robust cellular immune responses
      regardless of the transgene expressed, the cellular specificity of the promoter,
      and the muscle type injected. Viral purification by various methods did not
      diminish T cell-mediated infiltration. Our data indicate that AAV2 and AAV6
      capsid proteins can elicit primary cellular immune responses when injected into
      the skeletal muscle of random-bred dogs, and suggest the possibility of cellular
      immunity to AAV vectors in humans.

PMID- 17176212
TI  - Phytoestrogens and indicators of breast cancer prognosis.
AB  - Breast cancer incidence is lower and survival is longer in Asian women residing
      in Japan, China, or the Philippines than Caucasian women residing in the United
      States. Phytoestrogen intake has been examined as a possible reason for the
      disparity in breast cancer incidence and survival. This study examined the
      association between phytoestrogen intake prior to diagnosis of breast cancer and
      indicators of breast cancer prognosis (tumor size, estrogen and progesterone
      receptor status, histological grade, lymphovascular invasion, nodal spread, and
      stage) in 128 women, aged 40-79 yr, newly diagnosed with invasive breast cancer.
      After controlling for significant confounding factors, higher intakes of
      phytoestrogens were associated with favorable indicators of breast cancer. In
      women with higher intakes of phytoestrogens, there was a 32% reduction in the
      odds of being diagnosed with any stage of cancer other than stage 1 (95%
      confidence interval, CI = 0.49-0.93; P = 0.02), a 38% reduction in odds of being
      diagnosed with positive lymphovascular invasion (95% CI = 0.40-0.95; P = 0.03),
      and a 66% increase in the odds of being diagnosed with a positive progesterone
      receptor (95% CI = 1.06-2.58; P = 0.03). We conclude that phytoestrogen intake
      prior to diagnosis may improve prognosis of breast cancer.

PMID- 17176213
TI  - Colorectal cancer protective effects and the dietary micronutrients folate,
      methionine, vitamins B6, B12, C, E, selenium, and lycopene.
AB  - The data reported here were obtained from the case-control arm of a large,
      comprehensive, population-based investigation of colorectal cancer incidence,
      etiology, and survival, the Melbourne Colorectal Cancer Study, conducted in
      Melbourne, Australia. This part of the case-control study was designed to
      identify dietary factors associated with colorectal cancer risk in 715 incident
      cases compared with 727 age/sex frequency-matched randomly chosen community
      controls, in which a quantitative assessment of all foods eaten was made. New
      data are presented on the potential of two groups of micronutrients as protective
      agents, namely, those involved in DNA methylation, synthesis, and repair (folate,
      methionine, and vitamins B6 and B12) and those with antioxidant properties
      (selenium, vitamins E and C, and lycopene). The adjusted odds ratios showed that
      for folate there was significant protection for rectal cancer in second and third
      quintiles of consumption but not for colon cancer, and this was similar for
      methionine consumption. Vitamin B6 consumption was significantly protective for
      both colon and rectal cancer at the higher quintiles, and this was similar for
      vitamin B12. Dietary selenium was significantly protective at middle quintiles of
      consumption at both cancer sites. Dietary vitamins E and C were statistically
      significantly protective for both colon and rectal cancer at all levels of
      consumption, and for both vitamins there was a dose-response effect of increasing
      protection, particularly so for colon cancer. Lycopene was not associated with
      colorectal cancer risk. A combined model included vitamins E, C, and B12 and
      selenium as micronutrients protective for colorectal cancer and folate, which,
      however, showed an increased risk at the highest level of consumption. These data
      support the proposition that a diet containing the dietary micronutrients
      involved in DNA methylation (folate, methionine, and vitamins B6 and B12) and
      some of those with antioxidant properties (selenium and vitamins E and C) may
      have a role to play in lowering colorectal cancer risk and also that such
      protection can be achieved by dietary means alone.

PMID- 17176214
TI  - Relationship between calcium, lactose, vitamin D, and dairy products and ovarian
      cancer.
AB  - Few prospective studies of the relationship between intake of dairy foods,
      calcium, vitamin D, and lactose and ovarian cancer have been conducted, and
      results have been largely inconsistent. Two recent studies found significant
      increased risk with frequent dairy consumption and perhaps with high intakes of
      calcium or lactose. The authors investigated the association between these foods
      and nutrients and ovarian cancer risk among 31,925 subjects in the Breast Cancer
      Detection Demonstration Project follow-up cohort. Multivariable (MV) relative
      risks (RRs) adjusted for age, parity, and other factors were estimated using Cox
      proportional hazards models. Over an average follow-up of 8.3 yr, 146 incident
      ovarian cancer cases were confirmed. Higher intakes of total dairy food
      (comparing four or more servings per day vs. less than one serving per day) were
      associated with a statistically significant decreased risk of ovarian cancer,
      although the trend was not significant (MV RR = 0.42; 95% confidence interval
      (CI) = 0.20-0.89; P for trend = 0.07). Comparing extreme quartiles, we observed a
      statistically nonsignificant inverse association between high dietary calcium
      intake and ovarian cancer (RR = 0.67; 95% CI = 0.43, 1.04; P for trend = 0.08).
      No statistically significant relations were found for consumption of specific
      dairy foods, lactose, or vitamin D and ovarian cancer risk. The possibility of a
      decreased risk of ovarian cancer for dietary calcium merits further evaluation.

PMID- 17176215
TI  - Phytoestrogen exposure, polymorphisms in COMT, CYP19, ESR1, and SHBG genes, and
      their associations with prostate cancer risk.
AB  - Prospective phytoestrogen exposure was assessed using both biomarkers and
      estimates of intake in 89 British men recruited into the Norfolk arm of the
      European Prospective Investigation into Cancer and Nutrition study, men who
      subsequently developed prostate cancer. Results were compared with those from 178
      healthy men matched by age and date of recruitment. Levels of seven
      phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol,
      enterodiol, and enterolactone) were measured in spot urine and serum samples.
      Five single-nucleotide polymorphisms in COMT, CYP19, ESR1, and SHBG genes were
      genotyped. Urinary levels of all phytoestrogens correlated strongly with serum
      levels. Correlation coefficients ranged from 0.63 (glycitein) to 0.88 (daidzein)
      (P < 0.001). Urinary and serum levels correlated significantly with isoflavone
      intake assessed from food diaries (R = 0.15-0.20; P < 0.05) but not with that
      from a food-frequency questionnaire. Odds ratios for phytoestrogen exposure, as
      assessed using the four methods, were not significantly associated with prostate
      cancer risk (P = 0.15-0.94). Men with the CC genotype for the ESRI PvuII
      polymorphism had significantly higher risk for prostate cancer compared with men
      with the TT genotype [adjusted odds ratio = 4.65 (1.60-13.49); P = 0.005]. Our
      results utilizing a combined prospective exposure provide no evidence that
      phytoestrogens alter prostate cancer risk in British men, whereas the C allele
      for the PvuII polymorphism may be associated with increased risk.

PMID- 17176216
TI  - Dietary habits and pancreatic cancer risk in a cohort of middle-aged and elderly
      Japanese.
AB  - Few epidemiological studies have examined associations between diet and
      pancreatic cancer in Japan. In the Japan Collaborative Cohort Study for
      Evaluation of Cancer Risk, we evaluated the relationship between dietary factors,
      including meat, vegetable, and fruit intake, and the risk of pancreatic cancer
      deaths. Among the original cohort established between 1988 and 1990, 46,465 men
      and 64,327 women aged 40-79 yr were followed-up through December 31,1999. During
      1,042,608 person-years of follow-up, we documented 300 deaths from pancreatic
      cancer. A 33-item food-frequency questionnaire was used to assess dietary intake
      at the baseline survey. Cox proportional-hazards models were used to estimate the
      relative risks of pancreatic cancer death in relation to the intake frequency of
      food items. We did not observe an overall association between meat intake and
      pancreatic cancer risk. Except for a 50% decrease in risk associated with high
      fruit intake among men, we did not find other significant inverse relationships
      between vegetable and fruit intake and pancreatic cancer risk. Smoking did not
      modify the associations with dietary habits. Our study suggested that high
      consumption of pickles and wild edible plants, mainly bracken, might be related
      to increased pancreatic cancer risk; however, this finding should be confirmed in
      other epidemiological studies.

PMID- 17176217
TI  - Alcohol use and the risk of prostate cancer: results from the VITAL cohort study.
AB  - An association between alcohol consumption and prostate cancer risk remains
      uncertain. Although some studies have found that heavy alcohol consumption is
      associated with increased risk, a recent study reported that red wine consumption
      is associated with reduced risk. We examined the association between alcohol use
      and prostate cancer among 34,565 men, 50-76 yr old, in the Vitamins and Lifestyle
      (VITAL) cohort in Washington State. Alcohol consumption was ascertained by
      baseline questionnaire between October 2000 and December 2002. Incident prostate
      cancers (n = 816) as of December 31, 2004, were identified through the
      Surveillance, Epidemiology, and End Results cancer registry. Men who consumed
      more than one drink per month had a small increased risk of prostate cancer
      (hazard ratio, HR = 1.20; 95% confidence interval, CI = 1.02-1.40) compared with
      men who drank no alcohol or less than one drink per month. White wine consumption
      was associated with increased risk (HR for any vs. no white wine consumption =
      1.27; CI = 1.08-1.49). Red wine, liquor, and beer were not associated with
      prostate cancer nor was total alcohol consumed at ages 18, 30, and 45.
      Associations of alcohol use with prostate cancer are modest and complex. More
      detailed assessment of specific alcoholic beverages is warranted in future
      studies.

PMID- 17176218
TI  - Construction of a flavonoid database for assessing intake in a population-based
      sample of women on Long Island, New York.
AB  - Flavonoids have been hypothesized to reduce cancer risk. Previous epidemiological
      studies conducted to evaluate this hypothesis have not assessed all flavonoids,
      including classes that could contribute to intake among Americans, which would
      result in an underestimation of intake. This misclassification could mask
      variability among individuals, resulting in attenuated effect estimates for the
      association between flavonoids and cancer. To augment flavonoid and lignan intake
      estimates, we developed a database that can be used in conjunction with a food
      frequency questionnaire (FFQ). Coupling information derived from the available
      literature with the U.S. Department of Agriculture databases, we estimated
      content of 6 flavonoid classes and lignans for 50 food group items. We combined
      these estimates with responses from a modified Block FFQ that was self-completed
      in 1996-1997 by a population-based sample of women without breast cancer on Long
      Island, New York (n = 1,500). Total flavonoid and lignan content of food items
      ranged from 0 to 129 mg/100 g, and the richest sources were tea, cherries, and
      grapefruit. Individual intake estimates, from highest to lowest, were flavan-3
      ols, flavanones, flavonols, lignans, isoflavones, anthocyanidins, and flavones.
      Each class of flavonoids and lignans exhibited a wide range of intake levels.
      This database is useful to quantify flavonoid and lignan intake for other
      observational studies conducted in the United States that utilize the Block FFQ.

PMID- 17176219
TI  - Traditional home-brewed beer consumption and iron status in patients with
      esophageal cancer and healthy control subjects from Transkei, South Africa.
AB  - Consumption of home-brewed beer is associated with dietary iron excess and a high
      incidence of esophageal cancer in Transkei, South Africa. We examined the
      relationship between home-brewed beer consumption and body iron status in 234
      patients with esophageal squamous cell carcinoma and 595 control subjects
      residing in Transkei. Subjects were screened for iron overload using transferrin
      saturation >45%, and/or serum ferritin >200 microg/l for women and >300 microg/l
      for men. A questionnaire was administered to all subjects, and iron content of
      randomly selected home-brewed beer samples was determined. The iron content of
      home-brewed beer was 258-fold higher than the commercial Castle Lager beer
      produced by South African Breweries. The prevalence of home-brewed beer
      consumption was 30.1% in esophageal cancer patients and 15.5% in control subjects
      and was found not to be a risk factor for esophageal cancer after adjustment for
      age, sex, and tobacco consumption (male subjects, odds ratio= 1.6 (95% confidence
      interval [CI]: 0.7-4.5); female subjects, odds ratio=1.7 (95% CI: 0.7-4.5). Iron
      overload as determined by transferrin saturation and elevated serum ferritin was
      observed in 4.3% of patients with esophageal cancer and 0.7% of control subjects
      and was not associated with the consumption of home-brewed beer. Consumption of
      home-brewed beer is not a risk factor for esophageal cancer and is not linked
      with iron overload in either cancer patients or control subjects; however, iron
      overload is likely to result from a combination of dietary intake and a genetic
      component.

PMID- 17176221
TI  - Mixed tocopherols inhibit azoxymethane-induced aberrant crypt foci in rats.
AB  - Gamma (gamma) tocopherol, but not alpha (alpha) tocopherol (vitamin E), has
      previously been reported as an effective inhibitor of cyclooxygenase (COX) enzyme
      activity. In a pilot study of 17 rats, mixed tocopherols containing more than 50%
      gamma-tocopherol, added at 0.1% to an AIN-76A diet, produced a significant
      inhibition (about 55%) of azoxymethane-induced aberrant crypt foci in the colon
      of rats. Mixed tocopherols also reduced tetradecanoyl phorbol acetate-induced ear
      inflammation in mice when topically applied.

PMID- 17176220
TI  - Effects of soybean glyceollins and estradiol in postmenopausal female monkeys.
AB  - Glyceollins are a novel class of soybean phytoalexins with potential cancer
      protective antiestrogenic effects. The purpose of this study was to evaluate the
      estrogen-antagonist effects of glyceollin-enriched soy protein on biomarkers for
      breast cancer risk. Thirty female postmenopausal cynomolgus macaques were
      randomized to one of three dietary treatments for 3 wk: 1) estradiol (E2, 1
      mg/day) + casein/lactalbumin (control); 2) E2 + soy protein isolate (SPI)
      containing 194 mg/day isoflavonoids; and 3) E2 + glyceollin-enriched soy protein
      (GLY) containing 189 mg/day isoflavonoids + 134 mg/day glyceollins. Doses are
      expressed in calorically scaled human equivalents. Mean serum glyceollin
      concentrations at 4 h postfeeding were 134.2 +/- 34.6 nmol/L in the GLY group and
      negligible in the SPI group (P = 0.0007). Breast proliferation was significantly
      increased in the control group (+237%, P = 0.01) but not in the SPI group (+198%,
      P = 0.08) or GLY group (+36%, P = 0.18). Gene expression of trefoil factor 1 and
      progesterone receptor, two markers of estrogen receptor activity in breast
      epithelium, were also significantly higher in the control (P < 0.05 for both) but
      not in the GLY group. These preliminary findings suggest that soybean glyceollins
      are natural compounds with potential estrogen-modulating properties in the
      breast.

PMID- 17176223
TI  - Intestinal bifidobacteria that produce trans-9, trans-11 conjugated linoleic
      acid: a fatty acid with antiproliferative activity against human colon SW480 and
      HT-29 cancer cells.
AB  - Bifidobacterium breve species of human intestinal origin have the ability to
      synthesize cis-9, trans-11 (c9, t11) conjugated linoleic acid (CLA) from free
      linoleic acid. In this study, the ability of Bifidobacterium species to isomerize
      C(18) polyunsaturated fatty acids was investigated, and the antiproliferative
      activities of the two main microbially produced CLA isomers were assessed.
      Linoleic acid was converted principally to c9, t11 CLA and lesser amounts of t9,
      t11 CLA, whereas c9, t11 CLA was converted mainly to t9, t11 CLA. Likewise, t10,
      c12 CLA was converted principally to t9, t11 CLA, which was incorporated into the
      bacterial cell membranes. To examine the antiproliferative effect of the two main
      CLA isomers formed, SW480 and HT-29 human colon cancer cells were cultured in the
      presence of c9, t11 CLA and t9, t11 CLA. The t9, t11 CLA had a more potent
      antiproliferative effect than c9, t11 CLA. It is tempting to suggest that the
      ability of Bifidobacterium to produce such bioactive metabolites may be
      associated with the beneficial effects of bifidobacteria present in the human
      gastrointestinal tract.

PMID- 17176222
TI  - In vivo inhibition of growth of human tumor lines by flavonoid fractions from
      cranberry extract.
AB  - Edible fruits and berries may serve as sources for novel anticancer agents, given
      that extracts of these foods have demonstrated cytotoxic activity against tumor
      cell lines. Semipurified, flavonoid-rich extracts of cranberry (Vaccinia
      macrocarpa) were shown previously to arrest proliferation of tumor cells and
      induce apoptosis. However, the ability of cranberry flavonoids to inhibit tumor
      growth in vivo has not been reported other than in a preliminary report. As model
      systems for testing this activity, human tumor cell lines representative of three
      malignancies were chosen: glioblastoma multiforme (U87), colon carcinoma (HT-29),
      and androgen-independent prostate carcinoma (DU145). A flavonoid-rich fraction 6
      (Fr6) and a more purified proanthocyanidin (PAC)-rich fraction were isolated from
      cranberry presscake and whole cranberry, respectively, by column chromatography.
      Fr6 and PAC each significantly slowed the growth of explant tumors of U87 in
      vivo, and PAC inhibited growth of HT-29 and DU145 explants (P < 0.05), inducing
      complete regression of two DU145 tumor explants. Flow cytometric analyses of in
      vitro-treated U87 cells indicated that Fr6 and PAC could arrest cells in G1 phase
      of the cell cycle (P < 0.05) and also induce cell death within 24 to 48 h of
      exposure (P < 0.05). These results indicate the presence of a potential
      anticancer constituent in the flavonoid-containing fractions from cranberry
      extracts.

PMID- 17176224
TI  - Antiproliferative effects of citrus limonoids against human neuroblastoma and
      colonic adenocarcinoma cells.
AB  - Limonoids, a family of triterpenoids with putative anticancer properties, occur
      in fruits as glucosides and aglycones. Both highly purified forms were isolated
      from seeds and molasses of citrus fruits and tested for toxic effects against two
      human cancer cell lines, SH-SY5Y neuroblastoma and Caco-2 colonic adenocarcinoma,
      and a noncancerous mammalian epithelial Chinese hamster ovary (CHO) cells.
      Viability, as quantified by 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium
      reduction and light microscopy, was shortened significantly (P < 0.001) in cancer
      cells exposed to aglycones, viz., limonin, nomilin, obacunone, and
      deacetylnomilin. SH-SY5Y cells were more sensitive than Caco-2 cells to the
      limonoids, whereas noncancerous CHO cells showed hardly any change in cell
      numbers or cell morphology. Aglycone toxicity was dose dependent, but below the
      killing potential of glucosides. This observation correlated with a slower rate
      of induction of caspase 3/7 activity by aglycones. A flow cytometric analysis of
      SH-SY5Y cells treated with glucosides and aglycones showed an increased ploidy,
      which is consistent with enhancing chromosomal abnormalities. The results confirm
      that limonoids exert a strong multifaceted lethal action against cancer cells,
      but are relatively ineffective against CHO cells. Of the two, metabolites derived
      from glucosides are the more likely progenitors of an apoptosis response in situ.

PMID- 17176226
TI  - Equity and the social determinants of health.

PMID- 17176225
TI  - Effects of dietary intake of a fungal beta-D-glucan derivative on the level of
      DNA damage induced in primary rat hepatocytes by various carcinogens.
AB  - Water-soluble derivative of chitin-glucan complex used in our study,
      carboxymethyl chitin-glucan (CM-CG), enables oral administration without harmful
      side-effects, which can occur upon parenteral administration of the insoluble
      fungal beta-D-glucans. The aim of this study was to determine in ex vivo
      experiments the effects of dietary CM-CG on the level of DNA lesions in primary
      rat hepatocytes induced by various indirectly acting carcinogens. Multiorgan
      carcinogen benzo[a]pyrene (BaP); two hepatocarcinogens, dimethyldibenzocarbazole
      (diMeDBC) and N-nitrosomorpholine (NMOR); as well as a complex mixture of organic
      compounds adsorbed on ambient air particles (TP-S) were used for this purpose.
      The amount of DNA lesions was assessed using the comet assay and the micronucleus
      test. In addition, the mitotic indexes and the frequencies of necrotic and
      apoptotic cells were evaluated as well. Our results showed that the diet enriched
      with CM-CG (200 mg/kg of body weight) during 21 days did not induce any negative
      effect on DNA nor did the mitotic indexes and the frequencies of necrotic and
      apoptotic cells differ statistically from the controls. On the other hand, the
      hepatocytes isolated from CM-CG fed animals were more resistant to the action of
      all genotoxins used in our study [BaP (5-20 microM), diMeDBC (0.2-2 microM), NMOR
      (3.4-10.2 mM), TP-S (5-20 microM)]. We can conclude that in addition to the known
      immunopotentiating activity of beta-D-glucans, they can efficiently inhibit the
      genotoxicity of carcinogens requiring metabolic activation in rat heptocytes.

PMID- 17176227
TI  - A global perspective on health promotion and the social determinants of health.

PMID- 17176228
TI  - The social determinants of health: what are the three key roles for health
      promotion?

PMID- 17176229
TI  - Are social determinants of health the same as societal determinants of health?

PMID- 17176230
TI  - Building healthy and equitable societies: what Australia can contribute to and
      learn from the Commission on Social Determinants of Health.
AB  - The Commission on Social Determinants of Health (the Commission) was launched by
      the World Health Organization in 2005. It aims to support countries and global
      health partners to act on social factors leading to ill-health and health
      inequalities. Taking action on the social determinants of health is not new for
      Australia. This paper provides a description of the work of the first 18 months
      of the Commission and relevant Australian examples. Taking action on the social
      determinants of health is never simple or easy even in the most supportive of
      policy environments. The global focus of the Commission should ensure that
      knowledge and examples of successful action will be collected from a diverse
      range of country and policy environments, particularly low to middle-income
      countries. Given Australia's experience, we encourage practitioners to contribute
      to the deliberations of the Commission. It is also critical that Australian
      practitioners engage with the Commission's different actors and stakeholders,
      particularly knowledge networks, to derive important policy lessons from the
      knowledge generated by the Commission.

PMID- 17176231
TI  - Social determinants, political contexts and civil society action: a historical
      perspective on the Commission on Social Determinants of Health.
AB  - ISSUES ADDRESSED: To evaluate opportunities for action on social determinants of
      health (SDH) requires a historical perspective. Plans for addressing SDH should
      be developed with an awareness of past similar efforts and factors that
      contributed to their success or failure. METHODS: Review of published historical
      literature on analysis and action on SDH, in particular from the Latin American
      social medicine movement. RESULTS: In the period since World War II, global
      public health has oscillated between a social vision of health and a more
      individualistic, technological and medicalised model. Action on SDH was central
      to comprehensive primary health care as promulgated at the 1978 Alma-Ata
      conference and championed by the movement for 'Health for All by the Year 2000'.
      Subsequently, commitment to addressing SDH declined under the impact of
      restrictive interpretations of 'selective primary health care' and the pressure
      of neo-liberal economic and health policies. CONCLUSIONS: Through its critique of
      politically naive medical and public health approaches and of neo-liberal
      ideology, the Latin American social medicine tradition offers important lessons
      for today's efforts to advance action on SDH. Key lessons concern: (1) the model
      of praxis, consciously uniting reflection and action for political change; and
      (2) the importance of civil society and community participation in action on SDH.

PMID- 17176232
TI  - The role of the People's Health Movement in putting the social determinants of
      health on the global agenda.
AB  - The People's Health Movement (PHM) is a global network of people oriented health
      professionals and activists, academcis and researchers, campaigners and people
      organizations that have actively promoted the re-endorsement of the 'Health for
      All' principles of the Alma Ata Declaration and the importance of social
      determinants of health and health care. The paper outlines a series of ongoing
      advocacy initiatives through a PHM - WHO advocacy circle that has consistently
      since 2001 nudged WHO to reaffirm the Alma Ata principles and focus on the social
      determinants of health. This has led to an evolving dialogue with PHM and the
      setting up of the WHO commission on social determinants of health, in which the
      PHM, is actively engaged.

PMID- 17176233
TI  - The social determinants of health: is there a role for health promotion
      foundations?
AB  - ISSUE ADDRESSED: If they are to respond effectively to health inequities,
      organisations involved in health promotion need to refocus on the social
      determinants of health (SDH) and the distribution of resources for health.
      METHODS: This paper examines the potential of health promotion foundations
      (HPFs), a semi-autonomous arm of the state, to act at several policy and program
      intervention points to address the SDH and reduce health inequities. CONCLUSION:
      The public purpose, enterprise and innovation potential of health promotion
      foundations provides them with unique capacity to respond to SDH. In the complex
      and contested policy environment surrounding action on the determinants of
      health, the role that foundations can most usefully play is that of a change
      agent in a broader social movement seeking health equity.

PMID- 17176234
TI  - The role of health promotion: between global thinking and local action.
AB  - ISSUE ADDRESSED: The persistence of health inequities provides an ongoing
      challenge for health promotion. The dictum 'think globally, act locally' fails to
      recognise the significance of infrastructure and policy in linking global issues
      and local practices as a means of addressing health inequities. METHODS:
      Commentary and opinion. RESULTS: Through analytic tools and methods, health
      promotion has much to contribute to facilitating health-improving changes in
      social, economic and physical environments. Local actions provide excellent
      illustrations of organisational change and intersectoral action, and present the
      possibility that such actions could be widely implemented. While this has
      occurred on some issues, this is not usually the case. Political support, policy
      and infrastructure are required to link global ideas and local actions and
      overcome the impasse. Media advocacy is one example of an approach with potential
      to make these links and mobilise political support. CONCLUSIONS: Reframing media
      and political discussion, away from the dichotomy of individual responsibility
      and government intervention and towards acknowledging the social context of human
      behaviour, could contribute to policy and social environments with greater
      capacity to address inequities.

PMID- 17176235
TI  - The health system: what should our priorities be?
AB  - ISSUE ADDRESSED: The way the health system is organised is a critically important
      social determinant of health. Australia's current health system funding
      arrangements contain serious barriers to effective health promotion and chronic
      disease management. The consequences are most evident among disadvantaged people.
      Major health system reform is needed in Australia to rectify this problem.
      METHODS: This paper describes current mechanisms for funding health care in
      Australia and examines a recent reform experiment, the Co-ordinated Care Trials.
      It discusses why the trials were unsuccessful and identifies key criteria for
      future success. Three existing proposals for health system reform are assessed
      against these criteria - managed competition, a Commonwealth takeover of health
      and medical saving accounts. RESULTS: Successful reform of Australia's health
      system will need to ensure that more flexible services are delivered, changes are
      made on a large scale to affect demand and strong incentives to use cost
      effective services are put in place. Of the models considered, managed
      competition best meets these criteria and is most likely to reduce health
      disparities and improve health promotion and disease prevention. A Commonwealth
      takeover of health funding is a less ambitious alternative but because of this,
      it is also likely to have less impact. It is doubtful whether medical savings
      accounts meet any of the criteria for success and they would also require a
      fundamental change in the values that underpin the Austrlian health system.
      CONCLUSION: Recent reforms of Australia's health system have been too small and
      have had little impact. Although radical reform of the health system is
      politically unpalatable and extremely rare, it may be the only way Australia will
      be able to meet the health challenges of the 21st Century.

PMID- 17176236
TI  - Equity, by what measure?
AB  - Equity has in many instances been framed around the notion of fairness. But the
      metric used to determine what is fair leaves some people at a disadvantage
      because the things that they value are not always taken properly into account. If
      I value mangoes and you value oranges is a measure of fairness based on how many
      oranges I seek appropriate? If I am expected to give up my love of mangoes in
      order to get ahead is that fair? The debate about judging equity - about
      measuring fairness - needs to find the conceptual and methodological space to
      allow the voices and claims of the other to be heard.

PMID- 17176237
TI  - Sustainable communities: what should our priorities be?
AB  - ISSUE ADDRESSED: Reports of the degeneration of Earth's natural life-support
      systems have focused the minds of those in the scientific, political and general
      communities on how to avert a collapse. For many health promotion practitioners
      the effective unit of social change is the community, the interconnected web of
      people and place that makes up a human living system. The challenge lies in
      determining just what makes up a sustainable community under 21st Century
      conditions. METHOD: This paper reviews major national and international programs
      working towards sustainable communities, in order to arrive at strategies that
      establish the necessary interconnectedness and collective action within each
      individual community. RESULTS: Moving to a sustainable community under these
      conditions appears to meet the conditions of a 'wicked problem', that is, one
      that lies outside the present capacity of the society to resolve it. The move
      therefore calls for guided social change. CONCLUSION: The priorities for guiding
      the change to a sustainable community involve collective thinking and action as a
      mutual learning process among the affected individuals, communities, experts, and
      organisations, towards a holistic sustainability goal.

PMID- 17176238
TI  - Federal, State and Territory government responses to health inequities and the
      social determinants of health in Australia.
AB  - ISSUE ADDRESSED: Planned actions by governments can play an important part in
      addressing the social determinants of health and health inequities. We assess the
      extent to which Australian health departments are committed to health equity as a
      core value, and the extent to which strategic directions and policies show
      evidence of action and achievement in reducing health inequities and attention to
      the social determinants of health. METHODS: Key documents guiding each health
      department since 2000 were sought from a key informant in each jurisdiction
      (State/Territory/federal). An analysis was made of the content in terms of stated
      values, strategies, objectives, intended and current initiatives, collaborations,
      funding, and reporting of achievements in relation to the reduction of health
      inequities and the attention accorded to the social determinants of health.
      RESULTS: All jurisdictions are explicitly or implicitly committed to reducing
      health inequities and to addressing the social determinants of health to at least
      a limited extent. The extent of commitment varies from those who make a clear
      statement of the importance of achieving health equity at both whole-of
      government and health department level, to others who have extremely limited
      commitment. There is also variation in the extent to which directions are
      transformed into planned initiatives to improve health outcomes or access to
      health services for disadvantaged groups or areas, and variations in the degree
      of monitoring and evaluation. CONCLUSION: Although substantial health inequities
      exist in Australia there is explicit or implicit recognition of the underlying
      value of equity within all jurisdictions and some policies designed to increase
      health equity in all. However, in most jurisdictions health equity could be more
      explicitly incorporated into core government and health department strategies and
      initiatives, and there is room for the development of the capacity to monitor
      change over time in access to services, quality of care, and improved health
      outcomes.

PMID- 17176239
TI  - Smoking, not smoking: how important is where you live?
AB  - ISSUE ADDRESSED: To explore and describe the social-environmental influence upon
      the likelihood of smoking tobacco for the Australian experience, in particular,
      Victoria. METHODS: A multilevel (hierarchically structured regression) method was
      used. The micro-level units (characteristics of individuals) came from the annual
      surveys conducted by the Cancer Council of Victoria from 1990-97. The dependent
      variable was smoking status. The socio-demographic variables of age, marital
      status, education, employment status and ethnicity of individuals were used. The
      macro-level units (partitioned by postcode) came from the Australian Bureau of
      Statistics' Socioeconomic Index for Areas, split into quartiles. RESULTS:
      Residential neighbourhood had a unique but modest influence in the likelihood of
      smoking for both men and women. Also as the level of disadvantage increased
      within the residential area so did the odds of smoking for both men and women;
      however, the effect was not consistent. The odds of smoking were highest in the
      most disadvantaged areas for men, contrasting with women for whom the highest
      odds were in areas of more but not most disadvantage. CONCLUSIONS: The level of
      disadvantage of the residential neighbourhood has a unique, statistically
      significant influence, but not to the same degree as previously published
      Australian research. The effect is consistent across individual characteristics
      such as age and level of education for men. The effect is small and less
      consistent for women. Indeed, area of residence seems less important for women as
      a whole, suggesting differential influences according to gender.

PMID- 17176240
TI  - Evaluation of the Outreach School Garden Project: building the capacity of two
      Indigenous remote school communities to integrate nutrition into the core school
      curriculum.
AB  - ISSUE ADDRESSED: This paper describes the Outreach School Garden Project, which
      was conducted in two remote Indigenous school communities in north-west
      Queensland. This project integrated nutrition into the key learning areas of the
      core school curriculum by using a school-based garden as a nutritional education
      tool. METHODS: Evaluation was by a descriptive qualitative approach supplemented
      by some quantitative data consistent with Indigenous research methods. The
      objectives were linked to the Health Promoting Schools Framework, using concepts
      of community capacity building, action research, social capital and experiential
      learning. RESULTS: Nutrition was extensively integrated into the core school
      curriculum by the teaching staff, who required no specific nutrition knowledge or
      gardening skills prior to the implementation. Students' knowledge and skills in
      nutrition and gardening were increased over the six-month period and positive
      improvements in the physical and social environment at the school were observed.
      CONCLUSION: A school-based nutrition garden enables the teaching and learning of
      basic nutrition through the core school curriculum. This concept was an
      innovative, practical nutritional education tool to engage and build the capacity
      of Indigenous students, school staff and the broader community in nutrition.

PMID- 17176241
TI  - Scoping supermarket availability and accessibility by socio-economic status in
      Adelaide.
AB  - METHODS: We use a geographic information system to measure availability and
      accessibility of supermarkets in four case study local government areas (LGAs).
      The location of supermarkets is analysed in relation to residential dwellings,
      car ownership and in terms of travel distance along the road network. RESULTS:
      This methodology identifies differences in both availability and accessibility
      between and within LGAs. It shows that a local-level approach to the issue of
      food deserts is warranted and suggests that generalisations based on large
      geographic areas are unlikely to be meaningful. CONCLUSIONS: A significant number
      of households live in 'food deserts' in Adelaide and these can only be identified
      using a local-level approach.

PMID- 17176242
TI  - Food insecurity in three socially disadvantaged localities in Sydney, Australia.
AB  - ISSUE ADDRESSED: Food insecurity, now listed among the social determinants of
      health, compromises the health and well-being of affected Australians. The
      objective of this study was to determine the prevalence of food insecurity within
      an urban population of social disadvantage in readiness for a local health
      promotion response. METHODS: This was a cross-sectional survey conducted in three
      disadvantaged locations of south-western Sydney. Prevalence of food insecurity
      was assessed using both the 16-item US Household Food Security Survey Module and
      the single-item question previously used in national Australian health surveys.
      Bivariate and multiple logistic regression analyses were performed to determine
      associations between food insecurity and socio-demographic characteristics of the
      households. RESULTS: The 16-item US tool yielded a significantly higher food
      insecurity prevalence (21.9%, 95% CI 20.0-23.8) than the single-item Australian
      tool (15.8%, 95% CI 14.1-17.5). Compared with the former, the single-item
      Australian tool has high specificity (96%) yet low sensitivity (56.9%). In our
      three sites, food insecurity was strongly and independently associated with
      household capacity to save money (AOR=5.05). Local fruit and vegetable production
      (83.8%), nutrition education (83.9%), transport to food outlets (81.5%) and
      better public transport overall (76.3%) were most highly rated by 'food insecure'
      households as useful future strategies. CONCLUSION: The higher sensitivity of the
      US 16-item food security survey module relative to the single-item Australian
      tool indicates its potential for use in future Australian surveys of food
      insecurity.

PMID- 17176243
TI  - Utility stress as a social determinant of health: exploring the links in a remote
      Aboriginal community.
AB  - ISSUE ADDRESSED: The implications of the high cost of water on the poverty and
      subsequent health of Aboriginal residents in a remote community in Australia.
      METHODS: During 2003, a focus group session was held with adults at Umoona
      Aboriginal community in South Australia. Participants were asked to comment on
      key issues of concern in the provision of the domestic water supply. RESULTS: The
      Umoona community members in Coober Pedy identified the high cost of water and
      electricity as key hardship factors. CONCLUSIONS: Plans under the National Water
      Initiative to move to full cost recovery for water and the privatisation of
      public utilities may result in increased hardship for low-income groups such as
      Aboriginal people. Utility stress (difficulties paying water, electricity, gas or
      telephone accounts by the due date) increases poverty and relative deprivation,
      both key factors in the social determinants of health. Increased community
      service obligations (CSO) and rebates need to be made available to all low-income
      groups in order to reduce the negative impact of poverty.

PMID- 17176244
TI  - The war on obesity: a social determinant of health.
AB  - ISSUE ADDRESSED: The weight-centred health paradigm is an important contributor
      to the broader cultural paradigm in which corpulence is eschewed in favour of
      leanness. The desirability to reduce body fat or weight or to prevent gaining
      'excess' fat is driven by both aesthetic and health ideals. The 'war on obesity'
      is a broad health-based set of policies and programs designed to problematise
      'excess' body fat and create solutions to the 'problem'. There is a substantial
      body of literature that claims to demonstrate the harmful effects of 'excess'
      body fat. Recent critiques of 'obesity prevention' programs have highlighted the
      importance of focusing on environmental changes rather than individuals due in
      part to the risk of harmful consequences associated with individualistic, victim
      blaming approaches. Beyond this, there are suggestions that framing body weight
      as the source of health problems - known as the weight-centred health paradigm -
      is in itself a harmful approach. The range of harms includes body
      dissatisfaction, dieting, disordered eating, discrimination and death. Health
      promotion policies and programs that operate within the weight-centred paradigm
      have the potential to have a negative impact on the health and well-being of
      individuals and communities.

PMID- 17176245
TI  - Social determinants of health and health inequalities: what role for general
      practice?
AB  - This paper argues that general practice is potentially an important social
      determinant of health and health inequalities. The way it is influential is
      consistent with models of causal pathways in the way social and societal factors
      influence health. General practice clinical care can be thought of as a material
      resource. Evidence exists at many levels that this resource is inequitably
      distributed. But encounters in general practice are profoundly social processes,
      embedded in wider society. Debating and reflecting on the values underpinning
      relations between GP and patient may help challenge and illuminate wider
      inequitable processes in society that sustain inequalities in health.

PMID- 17176246
TI  - The NSW Social Determinants of Health Action Group: influencing the social
      determinants of health.

PMID- 17176247
TI  - Leukotriene B4 production in healthy subjects carrying variants of the
      arachidonate 5-lipoxygenase-activating protein gene associated with a risk of
      myocardial infarction.
AB  - Leukotrienes are implicated in the pathogenesis of coronary artery disease.
      Recently two haplotypes (HapA and HapB) in the gene encoding ALOX5AP
      (arachidonate 5-lipoxygenase-activating protein), the main regulator of 5
      lipoxygenase, have been associated with a doubling of the risk of myocardial
      infarction. Studies have also shown that treatment with a leukotriene inhibitor
      reduces biomarkers of coronary risk in patients carrying HapA, raising the
      possibility of developing genotype-specific therapy. In the present study, we
      examined whether carriage of HapA or HapB is associated with increased LTB(4)
      (leukotriene B(4)) production in healthy subjects. Age- and gender-matched
      healthy HapA carriers (n=21), HapB carriers (n=20) and non-A/non-B carriers
      (n=18), with no reported history of cardiovascular disease, were recruited
      following DNA screening of 1268 subjects from a population-based study. Blood
      neutrophils were isolated, and LTB(4) production was measured in response to
      stimulation with 1 mumol/l of the calcium ionophore A23187. There was no
      difference in the mean level for LTB(4) production in the three groups (non-A/non
      B, 24.9+/-8.3 ng/10(6) cells; HapA, 22.2+/-11.9 ng/10(6) cells; HapB, 19.8+/-4.8
      ng/10(6); P=0.14). The findings indicate that if either the HapA or the HapB
      haplotype of ALOX5AP indeed increases cardiovascular risk, then the mechanism is
      not simply due to a systematically observable effect of the haplotype on LTB(4)
      production in response to stimulation. The results suggest that knowledge of a
      patient's haplotype may not provide useful information on the probable clinical
      response to ALOX5AP inhibitors.

PMID- 17176248
TI  - Effect of chronic CB1 cannabinoid receptor antagonism on livers of rats with
      biliary cirrhosis.
AB  - Recent studies have shown that the activated endocannabinoid system participates
      in the increase in IHR (intrahepatic resistance) in cirrhosis. The increased
      hepatic production of vasoconstrictive eicosanoids is involved in the effect of
      endocannabinoids on the hepatic microcirculation in cirrhosis; however, the
      mechanisms of these effects are still unknown. The aim of the present study was
      to investigate the effects of chronic CB(1) (cannabinoid 1) receptor blockade in
      the hepatic microcirculation of CBL (common bile-duct-ligated) cirrhotic rats.
      After 1 week of treatment with AM251, a specific CB(1) receptor antagonist, IHR,
      SMA (superior mesenteric artery) blood flow and hepatic production of eicosanoids
      [TXB(2) (thromboxane B(2)), 6-keto PGF(1alpha) (prostaglandin F(1alpha)) and Cys
      LTs (cysteinyl leukotrienes)] were measured. Additionally, the protein levels of
      hepatic COX (cyclo-oxygenase) isoforms, 5-LOX (5-lipoxygenase), CB(1) receptor,
      TGF-beta(1) (transforming growth factor beta(1)), cPLA(2) [cytosolic PLA(2)
      (phospholipase A(2))], sPLA(2) (secreted PLA(2)) and collagen deposition were
      also measured. In AM251-treated cirrhotic rats, a decrease in portal venous
      pressure was associated with the decrease in IHR and SMA blood flow.
      Additionally, the protein levels of hepatic CB(1) receptor, TGF-beta(1), cPLA(2)
      and hepatic collagen deposition, and the hepatic levels of 5-LOX and COX-2 and
      the corresponding production of TXB(2) and Cys-LTs in perfusates, were
      significantly decreased after 1 week of AM251 treatment in cirrhotic rats.
      Furthermore, acute infusion of AM251 resulted in a decrease in SMA blood flow and
      an increase in SMA resistance in CBL rats. In conclusion, the chronic effects of
      AM251 treatment on the intrahepatic microcirculation were, at least partly,
      mediated by the inhibition of hepatic TGF-beta(1) activity, which was associated
      with decreased hepatic collagen deposition and the activated PLA(2)/eicosanoid
      cascade in cirrhotic livers.

PMID- 17176249
TI  - Oxygen-regulated protein 150 and prognosis following myocardial infarction.
AB  - ORP150 (oxygen-regulated protein 150) is a chaperonin expressed in tissues
      undergoing hypoxic or endoplasmic reticulum stress. In the present study, we
      investigated plasma levels of ORP150 in patients with AMI (acute myocardial
      infarction) and its relationship with prognosis, together with a known risk
      marker N-BNP (N-terminal pro-B-type natriuretic peptide). Plasma from 396
      consecutive patients with AMI was obtained for measurement of ORP150 and N-BNP.
      Mortality and cardiovascular morbidity (acute coronary syndromes/heart failure)
      was determined during follow-up. A specific ORP150 assay detected the 150 kDa
      protein in plasma extracts, including 3 and 7 kDa fragments. During follow-up
      (median, 455 days), 43 (10.9%) patients died. Both N-BNP and ORP150 levels were
      higher in those who died compared with the survivors [N-BNP, 724 (14.5-28840)
      compared with 6167 (154.9-33884) pmol/l (P<0.0005); ORP150, 257 (5.9-870.9)
      compared with 331 (93.3-831.8) pmol/l (P<0.001); values are medians (range)]. In
      a Cox regression model for mortality prediction, both N-BNP (odds ratio, 5.06;
      P<0.001) and ORP150 (odds ratio, 2.39; P<0.01) added prognostic information
      beyond creatinine and the use of thrombolytics. A Kaplan-Meier survival analysis
      revealed that ORP150 added prognostic information to N-BNP, especially in those
      with supra-median N-BNP levels. A simplified dual-marker approach with both
      markers below and either above or both above their respective medians effectively
      stratified mortality risk (log rank statistic for trend, 32.7; P<0.00005). ORP150
      levels were not predictive of other cardiovascular morbidity (acute coronary
      syndromes or heart failure). In conclusion, ORP150 and peptide fragments derived
      from it are secreted following AMI and provide independent prognostic information
      on mortality. High levels associated with endoplasmic reticulum/hypoxic stress
      predict a poor outcome.

PMID- 17176250
TI  - Biochemical and structural exploration of the catalytic capacity of Sulfolobus
      KDG aldolases.
AB  - Aldolases are enzymes with potential applications in biosynthesis, depending on
      their activity, specificity and stability. In the present study, the genomes of
      Sulfolobus species were screened for aldolases. Two new KDGA [2-keto-3
      deoxygluconate (2-oxo-3-deoxygluconate) aldolases] from Sulfolobus acidocaldarius
      and Sulfolobus tokodaii were identified, overexpressed in Escherichia coli and
      characterized. Both enzymes were found to have biochemical properties similar to
      the previously characterized S. solfataricus KDGA, including the condensation of
      pyruvate and either D,L-glyceraldehyde or D,L-glyceraldehyde 3-phosphate. The
      crystal structure of S. acidocaldarius KDGA revealed the presence of a novel
      phosphate-binding motif that allows the formation of multiple hydrogen-bonding
      interactions with the acceptor substrate, and enables high activity with
      glyceraldehyde 3-phosphate. Activity analyses with unnatural substrates revealed
      that these three KDGAs readily accept aldehydes with two to four carbon atoms,
      and that even aldoses with five carbon atoms are accepted to some extent. Water
      mediated interactions permit binding of substrates in multiple conformations in
      the spacious hydrophilic binding site, and correlate with the observed broad
      substrate specificity.

PMID- 17176251
TI  - Correlation between functional and binding activities of designer zinc-finger
      proteins.
AB  - Rapid progress in the ability to develop and utilize zinc-finger proteins with
      customized sequence specificity have led to their increasing use as tools for
      modulation of target gene transcription in the post-genomic era. In the present
      paper, a series of in vitro binding assays and in vivo reporter analyses were
      used to demonstrate that a zinc-finger protein can effectively specify a base at
      each position of the target site in vivo and that functional activity of the zinc
      finger protein as either a transcriptional repressor or activator is positively
      correlated with its binding affinity. In addition, this correlation can be
      extended to artificial engineered zinc-finger proteins. These data suggest that
      the binding affinity of designer zinc-finger proteins with novel specificity
      might be a determinant for their ability to regulate transcription of a gene of
      interest.

PMID- 17176252
TI  - Protein disulfide-isomerase mediates delivery of nitric oxide redox derivatives
      into platelets.
AB  - S-nitrosothiol compounds are important mediators of NO signalling and can give
      rise to various redox derivatives of NO: nitrosonium cation (NO+), nitroxyl anion
      (NO-) and NO* radical. Several enzymes and transporters have been implicated in
      the intracellular delivery of NO from S-nitrosothiols. In the present study we
      have investigated the role of GPx (glutathione peroxidase), the L-AT (L-amino
      acid transporter) system and PDI (protein disulfide-isomerase) in the delivery of
      NO redox derivatives into human platelets. Washed human platelets were treated
      with inhibitors of GPx, L-AT and PDI prior to exposure to donors of NO redox
      derivatives (S-nitrosoglutathione, Angeli's salt and diethylamine NONOate). Rapid
      delivery of NO-related signalling into platelets was monitored by cGMP
      accumulation and DAF-FM (4-amino-5-methylamino-2'7'-difluorofluorescein)
      fluorescence. All NO redox donors produced both a cGMP response and DAF-FM
      fluorescence in target platelets. NO delivery was blocked by inhibition of PDI in
      a dose-dependent manner. In contrast, inhibition of GPx and L-AT had only a
      minimal effect on NO-related signalling.PDI activity is therefore required for
      the rapid delivery into platelets of NO-related signals from donors of all NO
      redox derivatives. GPx and the L-AT system appeared to be unimportant in rapid NO
      signalling by the compounds used in the present study. This does not, however,
      exclude a possible role during exposure of cells to other S-nitrosothiol
      compounds, such as S-nitrosocysteine. These results further highlight the
      importance of PDI in mediating the action of a wide range of NO-related signals.

PMID- 17176253
TI  - Calcium regulates tertiary structure and enzymatic activity of human
      endometase/matrilysin-2 and its role in promoting human breast cancer cell
      invasion.
AB  - Human MMP-26 (matrix metalloproteinase-26) (also known as endometase or
      matrilysin-2) is a putative biomarker for human carcinomas of breast, prostate
      and other cancers of epithelial origin. Calcium modulates protein structure and
      function and may act as a molecular signal or switch in cells. The relationship
      between MMPs and calcium has barely been studied and is absent for MMP-26. We
      have investigated the calcium-binding sites and the role of calcium in MMP-26.
      MMP-26 has one high-affinity and one low-affinity calcium binding site. High
      affinity calcium binding was restored at physiologically low calcium conditions
      with a calcium-dissociation constant of 63 nM without inducing secondary and
      tertiary structural changes. High-affinity calcium binding protects MMP-26
      against thermal denaturation. Mutants of this site (D165A or E191A) lose
      enzymatic activity. Low-affinity calcium binding was restored at relatively high
      calcium concentrations and showed a K(d2) (low-affinity calcium-dissociation
      constant) value of 120 microM, which was accompanied with the recovery of
      enzymatic activity reversibly and tertiary structural changes, but without
      secondary structural rearrangements. Mutations at the low-affinity calcium
      binding site (C3 site), K189E or D114A, induced enhanced affinity for the Ca2+
      ion or an irreversible loss of enzymatic activity triggered by low-affinity
      calcium binding respectively. Mutation at non-calcium-binding site (V184D at C2
      site) showed that C2 is not a true calcium-binding site. Observations from
      homology-modelled mutant structures correlated with these experimental results. A
      human breast cancer cell line, MDA-MB-231, transfected with wild-type MMP-26 cDNA
      showed a calcium-dependent invasive potential when compared with controls that
      were transfected with an inactive form of MMP-26 (E209A). Calcium-independent
      high invasiveness was observed in the K189E mutant MDA-MB-231 cell line.

PMID- 17176254
TI  - Fluorinated and hemifluorinated surfactants as alternatives to detergents for
      membrane protein cell-free synthesis.
AB  - Hemifluorinated and fluorinated surfactants are lipophobic and, as such, non
      detergent. Although they do not solubilize biological membranes, they can, after
      conventional solubilization, substitute for detergents to keep membrane proteins
      soluble, which generally improves their stability [Breyton, Chabaud, Chaudier,
      Pucci and Popot (2004) FEBS Lett. 564, 312-318]. In the present study, we show
      that (hemi)fluorinated surfactants can be used for in vitro synthesis of membrane
      proteins: they do not interfere with protein synthesis, and they provide a
      suitable environment for MscL, a pentameric mechanosensitive channel, to fold and
      oligomerize to its native functional state. Following synthesis, both types of
      surfactants can be used to deliver MscL directly to pre-formed lipid vesicles.
      The electrophysiological activity of MscL synthesized in vitro in the presence of
      either hemi- or per-fluorinated surfactant is similar to that of the protein
      expressed in vivo.

PMID- 17176255
TI  - Dual role of the MgtC virulence factor in host and non-host environments.
AB  - MgtC is required for intramacrophage replication of intracellular pathogens and
      growth in low Mg(2+) medium. A link between these two phenotypes has been
      proposed due to putative Mg(2+) deprivation inside phagosome. MgtC is part of a
      family of proteins that share a conserved N-terminal transmembrane domain and a
      variable C-terminal domain. A combination of predictive and experimental
      approaches indicates that the Salmonella MgtC C-terminal domain is cytoplasmic,
      adopts a fold also found in metal transporters and RNA interacting domain, and
      does not bind Mg(2+). MgtC homologues from diverse gamma-proteobacteria,
      including the extracellular pathogens Yersinia pestis, Photorhabdus luminescens
      and Pseudomonas aeruginosa, have been expressed in a SalmonellaDeltamgtC strain.
      The Y. pestis MgtC fully replaced the Salmonella MgtC whereas P. luminescens or
      P. aeruginosa MgtC complemented only in low Mg(2+) medium, thus dissociating for
      the first time the two MgtC-related phenotypes. In addition, we identified single
      amino acids changes that prevent or promote MgtC role in macrophages without
      affecting MgtC role in low Mg(2+) culture. A SalmonellaDeltamgtC strain showed
      elongated and autoaggregated bacteria in low Mg(2+) medium but not in
      macrophages. Taken together our results suggest that MgtC has a dual role when
      bacteria localize in macrophages or low Mg(2+) environment.

PMID- 17176256
TI  - The human anionic antimicrobial peptide dermcidin induces proteolytic defence
      mechanisms in staphylococci.
AB  - Antimicrobial peptides (AMPs) represent a key component of innate host defence
      against bacterial pathogens. Bacterial resistance mechanisms usually depend on
      the characteristic positive charge of AMPs. However, several human cell types
      also produce anionic AMPs, mechanisms of resistance to which are poorly
      understood. Here we demonstrate that the skin commensal and leading nosocomial
      pathogen Staphylococcus epidermidis senses and efficiently inactivates the
      anionic AMP dermcidin. Dermcidin induced differential expression of global
      regulatory systems, leading to increased expression of proteases with the
      capacity to degrade dermcidin, particularly S. epidermidis SepA. A similar
      induction of extracellular proteolytic activity was found in Staphylococcus
      aureus, suggesting a common regulatory mechanism in staphylococci. Notably, human
      cationic AMPs also led to the activation of global regulators, but inactivation
      of dermcidin by SepA was much more effective than of the tested cationic
      peptides. The ability to react to the unusual, anionic dermcidin with effective
      countermeasures likely contributes to the extraordinary success of staphylococci
      as colonizers and infective agents on human epithelia. Our study indicates that
      staphylococci can react to human AMPs by specific mechanisms of resistance and
      establishes a crucial role for staphylococcal proteases in the interaction with
      human innate host defence.

PMID- 17176257
TI  - Gliding motility and polarized slime secretion.
AB  - Myxococcus leaves a trail of slime on agar as it moves. A filament of slime can
      be seen attached to the end of a cell, but it is seen only at one end at any
      particular moment. To identify genes essential for A motility, transposon
      insertion mutations with defective A motility were studied. Fifteen of the 33
      mutants had totally lost A motility. All these mutant cells had filaments of
      slime emerging from both ends, indicating that bipolar secretion prevents A
      motility. The remaining 18 A motility mutants, also produced by gene knockout,
      secreted slime only from one pole, but they swarmed at a lower rate than A(+) and
      are called 'partial' gliding mutants, or pgl. For each pgl mutant, the reduction
      in swarm expansion rate was directly proportional to the reduction in the
      coefficient of elasticotaxis. The pgl mutants have a normal reversal frequency
      and normal gliding speed when they move. But their probability of movement per
      unit time is lower than pgl(+) cells. Many of the pgl mutants are produced by
      transposon insertions in glycosyltransferase genes. It is proposed that these
      glycosyltransferases carry out the synthesis of a repeat unit polysaccharide that
      constitutes the slime.

PMID- 17176259
TI  - Phenotypic heterogeneity can enhance rare-cell survival in 'stress-sensitive'
      yeast populations.
AB  - Individual cells within isogenic microbial cultures exhibit phenotypic
      heterogeneity, an issue that is attracting intense interest. Heterogeneity could
      confer benefits, in generating variant subpopulations that may be better equipped
      to persist during perturbation. We tested this hypothesis by comparing the
      survival of wild-type Saccharomyces cerevisiae with that of mutants which are
      considered stress-sensitive but which, we demonstrate, also have increased
      heterogeneity. The mutants (e.g. vma3, ctr1, sod1) exhibited the anticipated
      sensitivities to intermediate doses of nickel, copper, alkaline pH, menadione or
      paraquat. However, enhanced heterogeneity meant that the resistances of
      individual mutant cells spanned a broad range, and at high stress occasional-cell
      survival in most of these populations overtook that of the wild type. Green
      fluorescent protein (GFP) reporter studies showed that this heterogeneity
      dependent advantage was not related to perturbation of buffered gene expression.
      Deletion strain screens combined with other approaches revealed that vacuolar
      alkalinization resulting from loss of Vma-dependent vacuolar H(+)-ATPase activity
      was not the cause of vma mutants' net stress sensitivities. An alternative Vma
      dependent resistance mechanism was found to suppress an influence of variable
      vacuolar pH on the metal resistances of individual wild-type cells. In addition
      to revealing new mechanisms of heterogeneity generation, the results demonstrate
      experimentally a benefit under adverse conditions that arises specifically from
      heterogeneity, and in populations conventionally considered to be disadvantaged.

PMID- 17176258
TI  - The Aspergillus fumigatus metacaspases CasA and CasB facilitate growth under
      conditions of endoplasmic reticulum stress.
AB  - We have examined the contribution of metacaspases to the growth and stress
      response of the opportunistic human mould pathogen, Aspergillus fumigatus, based
      on increasing evidence implicating the yeast metacaspase Yca1p in apoptotic-like
      programmed cell death. Single metacaspase-deficient mutants were constructed by
      targeted disruption of each of the two metacaspase genes in A. fumigatus, casA
      and casB, and a metacaspase-deficient mutant, DeltacasA/DeltacasB, was
      constructed by disrupting both genes. Stationary phase cultures of wild-type A.
      fumigatus were associated with the appearance of typical markers of apoptosis,
      including elevated proteolytic activity against caspase substrates,
      phosphatidylserine exposure on the outer leaflet of the membrane, and loss of
      viability. By contrast, phosphatidylserine exposure was not observed in
      stationary phase cultures of the DeltacasA/DeltacasB mutant, although caspase
      activity and viability was indistinguishable from wild type. The mutant retained
      wild-type virulence and showed no difference in sensitivity to a range of pro
      apoptotic stimuli that have been reported to initiate yeast apoptosis. However,
      the DeltacasA/DeltacasB mutant showed a growth detriment in the presence of
      agents that disrupt endoplasmic reticulum homeostasis. These findings demonstrate
      that metacaspase activity in A. fumigatus contributes to the apoptotic-like loss
      of membrane phospholipid asymmetry at stationary phase, and suggest that CasA and
      CasB have functions that support growth under conditions of endoplasmic reticulum
      stress.

PMID- 17176261
TI  - Recapitulation of cell signaling events associated with astrogliosis using the
      brain slice preparation.
AB  - Astroglial activation constitutes a dominant response to all types of injuries of
      the CNS. Despite the ubiquitous nature of this cellular reaction to neural
      injury, a little is known concerning the signaling mechanisms that initiate it.
      Recently, we demonstrated that astrocytic hypertrophy and enhanced expression of
      glial fibrillary acidic protein resulting from toxicant-induced neurodegeneration
      are linked to activation of the janus kinase (JAK)-signal transducer and
      activator of transcription-3 (STAT3) pathway. These observations implicate
      ligands at the gp130 receptor as potential upstream effectors of astrogliosis.
      Here we used the brain slice preparation to examine potential activators of the
      JAK-STAT3 pathway. Following incubation of freshly cut striatal slices in
      phosphate-free oxygenated buffer for up to 75 min, we found that slicing the
      striatum itself was a sufficient stimulus to initiate a rapid activation of the
      JAK-STAT3 pathway as assessed with immunoblots of pSTAT3((tyr705)) using phospho
      state specific antibodies. The mRNA for the gp130 cytokines, leukemia inhibitory
      factor, interleukin-6 and oncostatin M or the beta-chemokine, monocyte
      chemoattractive protein (CCl2) also were up-regulated in the slice. Moreover, we
      could enhance the activation of STAT3((tyr705)) by adding exogenous cytokines to
      the slice and we could inhibit phosphorylation of STAT3((tyr705)) by addition of
      tyrosine kinase inhibitors (Lav A and AG490) or neutralizing antibodies directed
      against leukemia inhibitory factor or oncostatin M. These data suggest that STAT3
      activation is an early event in slice-induced glial activation and establishes
      the brain slice preparation method as a reliable model to examine the signaling
      mechanisms that underlie glial activation.

PMID- 17176260
TI  - Human pregnancy-associated malaria-specific B cells target polymorphic,
      conformational epitopes in VAR2CSA.
AB  - Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected
      erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta by
      PAM-associated clonally variant surface antigens (VSA). Pregnancy-specific VSA
      (VSA(PAM)), which include the PfEMP1 variant VAR2CSA, are targets of IgG-mediated
      protective immunity to PAM. Here, we report an investigation of the specificity
      of naturally acquired immunity to PAM, using eight human monoclonal IgG1
      antibodies that react exclusively with intact CSA-adhering IEs expressing
      VSA(PAM). Four reacted in Western blotting with high-molecular-weight (> 200 kDa)
      proteins, while seven reacted with either the DBL3-X or the DBL5-epsilon domains
      of VAR2CSA expressed either as Baculovirus constructs or on the surface of
      transfected Jurkat cells. We used a panel of recombinant antigens representing
      DBL3-X domains from P. falciparum field isolates to evaluate B-cell epitope
      diversity among parasite isolates, and identified the binding site of one
      monoclonal antibody using a chimeric DBL3-X construct. Our findings show that
      there is a high-frequency memory response to VSA(PAM), indicating that VAR2CSA is
      a primary target of naturally acquired PAM-specific protective immunity, and
      demonstrate the value of human monoclonal antibodies and conformationally intact
      recombinant antigens in VSA characterization.

PMID- 17176262
TI  - Molecular cloning of prostaglandin EP3 receptors from canine sensory ganglia and
      their facilitatory action on bradykinin-induced mobilization of intracellular
      calcium.
AB  - We previously demonstrated that the activation of prostaglandin E-prostanoid-3
      (EP3) receptor sensitized the canine nociceptor response to bradykinin (BK). To
      elucidate the molecular mechanism for this sensitization, we cloned two cDNAs
      encoding EP3s with different C-terminals, from canine dorsal root ganglia, and
      established the transformed cell lines stably expressing them. In both
      transformants, EP3 agonist did not increase intracellular cAMP levels, but it
      attenuated forskolin-dependent cAMP accumulation in a pertussis toxin (PTX)
      sensitive manner and increased intracellular calcium levels in a PTX-resistant
      manner, indicating that both EP3s can couple with Gi and Gq, but not with Gs
      proteins. As the nociceptor response to BK is mediated by BK B2 receptor, it was
      transfected into the transformants and the effects of EP3 agonist on BK-dependent
      calcium mobilization were investigated. When BK was applied twice with a 6-min
      interval, the second response was markedly attenuated. Pre-treatment with EP3
      agonist had no effect on the initial response, but restored the second response
      in a PTX-sensitive manner. A protein kinase A inhibitor mimicked the effect of
      EP3 agonist. These results demonstrate that the activation of EP3 restores the
      response to BK by attenuating the desensitization of BK B2 receptor activity via
      Gi protein.

PMID- 17176263
TI  - Stimulation of group I mGlu receptors in the ventrotegmental area enhances
      extracellular dopamine in the rat medial prefrontal cortex.
AB  - Group I mGlu receptors have been implicated in the control of brain dopamine
      release. However, the receptor subtype involved and the precise site of action
      have not been determined. In this study we show that (R,S)3,5
      dihydroxyphenylglycine (DHPG; 6 and 60 nmol ICV), a selective group I mGlu
      receptor agonist, raised extracellular dopamine respectively by 176% and 243% of
      basal values in the medial prefrontal cortex as assessed by in vivo microdialysis
      in conscious rats. (R,S)2-chloro-5-hydroxyphenylglycine (60 nmol ICV), a
      selective mGlu5 receptor agonist, raised extracellular dopamine by 396% of basal
      values. Intra-VTA DHPG (0.6-6 nmol) mimicked ICV injection whereas intracortical
      infusion (1-1000 micromol/L) had no effect. DHPG-induced rise of extracellular
      dopamine was reversed by tetrodotoxin and by the selective mGlu1 and mGlu5
      receptor antagonists 7(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate (CPCCOEt)
      and 2-methyl-6-(phenylethynyl)pyridine (MPEP) either ICV or into the
      ventrotegmental area (VTA), suggesting that neuronal release and both mGlu1 and
      mGlu5 receptors were involved. These results support the existence of functional
      mGlu1 and mGlu5 receptors in the VTA regulating the release of dopamine in the
      medial prefrontal cortex.

PMID- 17176264
TI  - Post-ischaemic treatment with the cyclooxygenase-2 inhibitor nimesulide reduces
      blood-brain barrier disruption and leukocyte infiltration following transient
      focal cerebral ischaemia in rats.
AB  - Several studies suggest that cyclooxygenase (COX)-2 plays a pivotal role in the
      progression of ischaemic brain damage. In the present study, we investigated the
      effects of selective inhibition of COX-2 with nimesulide (12 mg/kg) and selective
      inhibition of COX-1 with valeryl salicylate (VAS, 12-120 mg/kg) on prostaglandin
      E(2) (PGE(2)) levels, myeloperoxidase (MPO) activity, Evans blue (EB)
      extravasation and infarct volume in a standardized model of transient focal
      cerebral ischaemia in the rat. Post-ischaemic treatment with nimesulide markedly
      reduced the increase in PGE(2) levels in the ischaemic cerebral cortex 24 h after
      stroke and diminished infarct size by 48% with respect to vehicle-treated animals
      after 3 days of reperfusion. Furthermore, nimesulide significantly attenuated the
      blood-brain barrier (BBB) damage and leukocyte infiltration (as measured by EB
      leakage and MPO activity, respectively) seen at 48 h after the initial ischaemic
      episode. These studies provide the first experimental evidence that COX-2
      inhibition with nimesulide is able to limit BBB disruption and leukocyte
      infiltration following transient focal cerebral ischaemia. Neuroprotection
      afforded by nimesulide is observed even when the treatment is delayed until 6 h
      after the onset of ischaemia, confirming a wide therapeutic window of COX-2
      inhibitors in experimental stroke. On the contrary, selective inhibition of COX-1
      with VAS had no significant effect on the evaluated parameters. These data
      suggest that COX-2 activity, but not COX-1 activity, contributes to the
      progression of focal ischaemic brain injury, and that the beneficial effects
      observed with non-selective COX inhibitors are probably associated to COX-2
      rather than to COX-1 inhibition.

PMID- 17176265
TI  - Induction of axonal differentiation by silencing plasma membrane-associated
      sialidase Neu3 in neuroblastoma cells.
AB  - A reduction of 70% of the plasma membrane-associated sialidase Neu3 activity, due
      to a corresponding reduction of the enzyme expression by transducing cells with a
      short hairpin RNA encoding a sequence target (complementary messenger of mouse
      Neu3), caused neurite elongation in Neuro2a murine neuroblastoma cells. The
      differentiation process was accompanied in parallel by an increase of the
      acetylcholinesterase activity, a moderate increase of the c-Src expression and by
      the presence of the axonal marker tau protein on the neurites. The sphingolipid
      pattern and turnover in transduced and control cells were characterized by thin
      layer chromatography, mass spectrometry and metabolic radiolabeling after feeding
      cells with tritiated sphingosine. Control cells contained about 2 nmol of
      gangliosides/mg cell protein. GM2 was the main compound, followed by GD1a, GM3
      and GM1. In Neu3 silenced cells, the total ganglioside content remained quite
      similar, but GM2 increased by 54%, GM3 remain constant, and GM1 and GD1a
      decreased by 66% and 50%, respectively. Within the organic phase sphingolipids,
      ceramide decreased by 50%, whereas the sphingomyelin content did not change in
      Neu3 silenced cells.

PMID- 17176267
TI  - The C-terminus of alpha2-antiplasmin interacts with endothelial cells.
AB  - The serpin, alpha(2)-antiplasmin (alpha(2)AP), has an extended C-terminus
      relative to other inhibitors. This 51-residue region contains an RGD sequence;
      such sequences constitute a key recognition sequence for cell adhesion, mediated
      through integrins. In the present study, this sequence was expressed in
      Escherichia coli and its binding to endothelial cells and whether binding depends
      on the RGD sequence was investigated. Binding to the surface of human umbilical
      vein endothelial cells (HUVEC-C) was observed by flow cytometry and
      immunohistochemistry. Binding studies on immobilised cells showed specific and
      RGD-dependent binding of the peptides to HUVEC-C. The binding of the wild-type
      peptide to the HUVEC-C was significantly higher than that of a mutant peptide, in
      which RGD was replaced by SAA (P < 0.05, n = 4). Similarly,
      ethylenediaminetetraacetic acid decreased the binding of the wild-type peptide (P
      < 0.05, n = 4). The binding was competed out by full-length alpha(2)AP,
      fibronectin and anti-alpha(5)beta(1). This is the first evidence of binding of
      the C-terminus of alpha(2)AP to endothelial cells via its RGD sequence, with most
      but not all of the binding being integrin-mediated. We speculate that this
      interaction with alpha(2)AP may potentially play a role in the control of
      cellular fibrinolysis by regulating local plasmin activity on cell surfaces.

PMID- 17176266
TI  - Novel methodology for assessment of prophylactic platelet transfusion therapy by
      measuring increased thrombus formation and thrombin generation.
AB  - Currently, patients developing severe thrombocytopenia during chemotherapy
      treatment are prophylactically transfused with platelets. We developed two
      platelet function tests to report the improved haemostasis in the transfused
      patients, which were capable of detecting aberrant responsiveness of the
      platelets after transfusion. First, in a whole-blood flow test, platelet adhesion
      and thrombus formation were determined under high-shear flow conditions. Second,
      the procoagulant function of platelets was assayed in platelet-rich plasma by
      measurement of thrombin generation. Experimental conditions were established,
      where flow-induced adhesion and thrombin generation test parameters increased
      semi-linearly with the platelet concentration, and informed on the activation
      properties of platelets. The transfusion effects were evaluated for 38
      thrombocytopenic patients, who were transfused with platelets stored in plasma or
      in synthetic medium (platelet additive solution II). In most but not all
      patients, transfusion resulted in increased adhesion and thrombus formation, as
      well as in improved platelet-dependent coagulation. Taken together, the increase
      in platelet count after transfusion explained 57% of the overall improvement in
      platelet function. In acute graft-versus-host disease, thrombus formation was
      normal, while platelet-dependent coagulation was higher than expected. We
      conclude that assessment of flow-induced adhesion and thrombin generation in
      acquired thrombocytopenia adequately determines the improved haemostatic activity
      by transfused platelets.

PMID- 17176268
TI  - An unusual cutaneous presentation of cat-scratch disease.

PMID- 17176269
TI  - Flare and change of psoriasis morphology during the course of treatment with
      tumour necrosis factor blockers.
AB  - Tumour necrosis factor (TNF) blockers represent an exciting advance in the
      management of psoriasis. However, the safety profile of these drugs is not
      completely established. We present a review of the literature, and report on
      eight patients: two with the unexpected appearance of psoriasis, and the
      remaining six with exacerbation and change in morphology of their existing
      psoriasis, all of which occurred during treatment with the TNF blockers
      adalimumab, etanercept and infliximab. The two new cases, neither of whom had any
      personal or family history of psoriasis, developed pustular psoriasis on the
      palms and/or soles. The other six patients, previously diagnosed with severe
      chronic plaque psoriasis (four patients), generalized pustular psoriasis (one)
      and erythrodermic psoriasis (one), developed eruptive guttate psoriasis between
      15 days and 18 months after the beginning of therapy. These patients had never
      before presented guttate-type psoriatic lesions, and the lesions appeared in
      areas of the body that were free of psoriatic plaques at baseline.

PMID- 17176270
TI  - Cutaneous necrosis in a young woman.

PMID- 17176277
TI  - Laparoscopic colposuspension and tension-free vaginal tape: a systematic review.
AB  - BACKGROUND: Advances in surgical techniques have led to the availability of a
      number of minimal-access procedures to treat urodynamic stress incontinence
      (USI). These procedures have been individually compared with the 'gold standard'
      open Burch colposuspension; however, it now seems appropriate to compare like
      with like and compare these minimal-access techniques with each other.
      OBJECTIVES: To determine the effectiveness of laparoscopic colposuspension with
      tension-free vaginal tape (TVT) for the treatment of USI. SEARCH STRATEGY:
      Randomised trials in woman with USI, which compared laparoscopic colposuspension
      with TVT in the arms of the trial, were identified from the Cochrane Incontinence
      Review Group's Specialised Register of Controlled Trials. SELECTION CRITERIA: The
      trials were evaluated for methodological quality and appropriateness for
      inclusion by the reviewers using the Incontinence Group's assessment criteria.
      DATA COLLECTION AND ANALYSIS: The data were extracted independently, and when
      appropriate, meta-analysis was undertaken to calculate pooled estimates and their
      confidence intervals (CI). The main outcomes measured were: subjective cure,
      objective cure, quality of life (QoL) measurements, surgical outcomes and health
      economic measures. MAIN RESULTS: Seven trials compare laparoscopic
      colposuspension (n= 264) with TVT (n= 290). There was no statistically
      significant difference in the reported subjective cure rate between laparoscopic
      colposuspension and TVT within 18 months (relative risk [RR] 1.12, 95% CI 0.98
      1.29). However, within the same time period, the overall objective cure rate was
      statistically significantly higher for TVT (RR 1.16, 95% CI 1.07-1.25). There
      were no significant differences between the two procedures with regards to
      perioperative complication, de novo detrusor overactivity, voiding dysfunction,
      procedural costs and QoL scores. However, TVT procedure is quicker to perform and
      has a shorter hospital stay. CONCLUSIONS The evidence so far appears to be in
      favour of the TVT as the minimal-access technique of choice for USI in comparison
      with laparosopic colposuspension; however, long-tem data are needed. Further well
      designed trials with standardized outcomes are required to draw accurate
      conclusions from this comparison.

PMID- 17176278
TI  - Three hundred and thirty cycles of preimplantation genetic diagnosis for serious
      genetic disease: clinical considerations affecting outcome.
AB  - OBJECTIVE: To report on our experience with preimplantation genetic diagnosis
      (PGD) cycles performed for serious genetic disease in relation to the clinical
      factors affecting outcome. DESIGN: Retrospective review of data from a single
      centre. SETTING: Tertiary referral PGD centre in a London teaching hospital.
      METHODS: The PGD cycles included 172 cycles for chromosome rearrangements, 96
      cycles for single-gene disorders and 62 cycles for X-linked disorders. In vitro
      fertilisation was the preferred method in chromosome rearrangement and X-linked
      cases, while intra cytoplasmic sperm injection was used in all single-gene
      disorders. Appropriate in situ hybridisation fluorescence probes were used in
      chromosome rearrangement and X-linked cases and polymerase chain reaction was
      used in single-gene disorders. All pregnancies were followed till delivery. MAIN
      OUTCOME MEASURE: Live birth rate per PGD cycle started. RESULTS: Eighty-six
      percent of cycles started (283) reached oocyte retrieval and 3743 eggs were
      collected, of which 2086 fertilised normally (55.7%). Two hundred and fifty
      cycles (76%) had embryos sutiable for biopsy on day 3 of in vitro culture, 1714
      embryos were biopsied, and in 205 cycles (62%), there was at least one unaffected
      embryo available for transfer, resulting in 90 pregnancies, 68 clinical
      pregnancies and 58 live birth. The live birth rate was 18% per cycle started, 21%
      per egg retrieval and 28% per embryo transfer which significantly affected the
      live birth outcome. Woman age, number of eggs collected and achieving
      cryopreservation of surplus embryos had no statistically significant effect on
      treatment outcome. CONCLUSIONS: The live birth outcome of PGD cycles for serious
      genetic disorder is modest and is affected by the number of embryos genetically
      suitable for transfer.

PMID- 17176279
TI  - A randomised trial of carbetocin versus syntometrine in the management of the
      third stage of labour.
AB  - OBJECTIVE: Syntometrine is an effective uterotonic agent used in preventing
      primary postpartum haemorrhage but has adverse effects including nausea,
      vomiting, hypertension and coronary artery spasm. Carbetocin is a newly developed
      long-acting oxytocin analogue that might be used as an uterotonic agent. We
      compare the efficacy and safety of intramuscular (IM) carbetocin with IM
      syntometrine in preventing primary postpartum haemorrhage. DESIGN: Prospective,
      double-blinded, randomised controlled trial. SETTING: Delivery suite of a
      university-based obstetrics unit. POPULATION: Women with singleton pregnancy
      achieving vaginal delivery after and throughout 34 weeks. METHODS: Three hundred
      and twenty-nine eligible women were randomised to receive either a single dose of
      100 microgram IM carbetocin or 1 ml IM syntometrine (a mixture of 5 iu oxytocin
      and 0.5 mg ergometrine) at the end of second stage of labour. MAIN OUTCOME
      MEASURES: Difference in haemoglobin drop measured 2 days after delivery between
      the two groups. RESULTS: There was no difference in the drop of haemoglobin
      concentration within the first 48 hours between the two groups. The incidence of
      additional oxytocic injections, postpartum haemorrhage (blood loss > or = 500 ml)
      and retained placenta were also similar. The use of carbetocin was associated
      with significant lower incidence of nausea (relative risk [RR] 0.18, 95%
      confidence interval [CI] 0.04-0.78), vomiting (RR 0.1, 95% CI 0.01-0.74),
      hypertension 30 minutes (0 versus 8 cases, P < 0.01) and 60 minutes (0 versus 6
      cases, P < 0.05) after delivery but a higher incidence of maternal tachycardia
      (RR 1.68, 95% CI 1.03-3.57). CONCLUSIONS: IM carbetocin is as effective as IM
      syntometrine in preventing primary postpartum haemorrhage after vaginal delivery.
      It is less likely to induce hypertension and has a low incidence of adverse
      effect. It should be considered as a good alternative to conventional uterotonic
      agents used in managing the third stage of labour.

PMID- 17176280
TI  - Ovarian reserve tests for predicting fertility outcomes for assisted reproductive
      technology: the International Systematic Collaboration of Ovarian Reserve
      Evaluation protocol for a systematic review of ovarian reserve test accuracy.
AB  - BACKGROUND: The presence of a wide range of tests of ovarian reserve suggests
      that no single test provides a sufficiently accurate result. Many tests are used
      without reference to an evidence base. So far, individual studies conducted on
      these tests are too small to give precise estimates of prognostic accuracy.
      OBJECTIVES: To systematically assess the accuracy of the available tests of
      ovarian reserve in terms of prediction of fertility outcomes. SEARCH STRATEGY:
      The search will be conducted using the name of the respective index test being
      studied (as listed on the MESH database), if more than 2000 citations are listed,
      'ovary' and or 'ovarian', 'fertility' and or 'reserve' will be combined with the
      original search term as required. Studies of the accuracy of tests of ovarian
      reserve will be obtained without language restrictions from 1980 to 2005 using
      the following electronic databases and Ovid software: MEDLINE, EMBASE, PUBmed,
      Biological extracts, Pascal, Cochrane Library (CDSR, DARE, CCTR, HTA), Best
      Evidence databases, SCISEARCH, Conference Proceedings (ISI Proceedings,
      Healthstar, Current Contents, Science Citation Index, Cancerlit and Econlit and
      NHS Economic Evaluation database. The National Research Register, the Medical
      Research Council's Clinical Trials Register, MEDION, DARE, and the US Clinical
      Trials register. SELECTION CRITERIA: Studies will be selected if accuracy of
      tests are compared with a reference standard and include data that can be
      abstracted into a two-by-two table to calculate sensitivity and specificity. The
      studies to be included in this review will examine one of the following index
      'tests' within a study population of women undergoing assisted reproductive
      technology: * Clinical variables--age, history of cancelled cycles. * Basal blood
      tests--follicle-stimulating hormone (FSH), lutenising hormone (LH), FSH:LH
      ratios, estradiol (E(2)), inhibin A and B, progesterone (P(4)), P(4):E(2) ratios,
      antimullerian hormone, testosterone, vascular endothelial growth factor, insulin
      like growth factor-1:insulin-like growth factor binding protein-1 ratios. *
      Dynamic tests--clomiphene citrate challenge test, gonadotropin analogue
      stimulating test, exogenous FSH ovarian reserve test. * Ultrasound tests-antral
      follicle count, ovarian volume, ovarian stromal peak systolic velocity, including
      waveform and pulsatility index, ovarian follicular vascularity. * Histology-
      ovarian biopsy. Data collection and analysis Two independent reviewers will
      perform quality assessment and data extraction. Prognostic accuracy will be
      determined by calculating positive and negative likelihood ratios for the
      following outcomes or reference standards: live birth, ongoing pregnancy,
      clinical pregnancy, biochemical pregnancy, embryos available for transfer, eggs
      obtained at oocyte retrieval, cycles cancelled prior to oocyte retrieval. Main
      results and conclusions N/A.

PMID- 17176282
TI  - Nonstandardised terminology in the BJOG.

PMID- 17176283
TI  - Acronyms.

PMID- 17176285
TI  - Topical tacrolimus in the management of lichen sclerosus.

PMID- 17176286
TI  - Late miscarriage and preterm birth after treatment with clindamycin: a randomised
      consent design study according to Zelen.

PMID- 17176295
TI  - Sildenafil inhibits the up-regulation of phosphodiesterase type 5 elicited with
      nicotine and tumour necrosis factor-alpha in cavernosal vascular smooth muscle
      cells: mediation by superoxide.
AB  - OBJECTIVES: To determine whether there is an association between vascular
      phosphodiesterase type 5 (PDE-5) and NADPH oxidase (NOX) in cavernosal vascular
      smooth muscle cells (CVSMCs), and to study the actions of the PDE-5 inhibitor
      sildenafil; the pro-erectile actions of nitric oxide (NO) are reduced by PDE-5
      which hydrolyses cGMP to inactive GMP, thus an up-regulation of PDE-5 and over
      production of O(2)(-) derived from NOX might promote erectile dysfunction (ED).
      MATERIALS AND METHODS: To study the effects of nicotine and tumour necrosis
      factor-alpha (TNF-alpha) on superoxide (O(2)(-)) production and PDE-5 expression,
      CVSMCs from rabbit penis were incubated with nicotine or TNF-alpha, and
      superoxide dismutase (SOD), catalase, sildenafil citrate, or apocynin (NADPH
      inhibitor) for 16 h. The expression of PDE-5 and of glyceraldehyde-3-phosphate
      dehydrogenase (internal standard) was assessed using Western blotting. O(2)(-)
      was measured spectrophotometrically. RESULTS: After a 16-h incubation, both
      nicotine (maximal at 10 microm) and TNF-alpha (10 ng/mL) significantly increased
      O(2)(-) formation in CVSMCs; this effect was blocked by co-incubating with SOD,
      catalase, and sildenafil (1 microm). Apocynin also inhibited O(2)(-) formation
      when added after 16-h incubation with nicotine (10 microm) or TNF-alpha. PDE-5
      expression was also significantly increased in CVSMCs incubated with nicotine and
      TNF-alpha. This effect was negated by 16-h co-incubation with SOD, catalase,
      apocynin, and sildenafil. CONCLUSIONS: Nicotine and TNF-alpha up-regulate PDE-5
      expression in CVSMCs through an a priori up-regulation of NOX and formation of
      O(2)(-). As PDE-5 hydrolyses cGMP, this effect might 'blunt' the pro-erectile
      actions of NO. Sildenafil inhibits O(2)(-) formation, and 'normalizes' PDE-5
      expression. This represents a novel pathogenic mechanism underlying ED, and a
      novel mechanism of action of sildenafil.

PMID- 17176296
TI  - Diabetes and the urologist: a growing problem.
AB  - The incidence of diabetes continues to increase dramatically; this incidence is
      predominantly of the type-2 form which clusters together with other comorbidities
      of hypertension and lipid abnormalities, to form the metabolic syndrome. These
      conditions will have an increasing impact on urological practice, with erectile
      dysfunction, hypogonadism, voiding difficulties and urinary tract infections all
      more common in these patients. These symptoms might be the initial presentation
      of previously undiagnosed diabetes and it is important to recognise this
      condition early to avoid later complications including end-stage renal failure.

PMID- 17176297
TI  - Increasing the knowledge in managing hyperpigmentary disorders: a report from the
      Pigmentary Disorders Academy.

PMID- 17176298
TI  - Confusions about colour: a classification of discolorations of the skin.

PMID- 17176299
TI  - Ethnic considerations in the treatment of Hispanic and Latin-American patients
      with hyperpigmentation.
AB  - Latin-Americans have a heterogeneous ancestry that is defined by their place of
      domicile, while Hispanics are defined as those persons of Spanish descent. These
      two groups have a diverse range of skin phototypes and pigmentation and are prone
      to an increased incidence of melasma and post-inflammatory hyperpigmentation.
      Little research has been conducted to evaluate the frequency, course, effects,
      tolerability and treatment response of skin diseases in Hispanic and Latin
      American populations. From the limited data that are available it is considered
      that the treatment of melasma in these two groups does not differ from the
      general population. First-line therapy of melasma should consist of effective
      topical therapies, mainly a fixed triple combination of hydroquinone, retinoic
      acid and fluocinolone acetonide. Where patients have either sensitivity or triple
      combination therapy is unavailable, other compounds with dual ingredients may be
      considered as an alternative. Options for second-line therapy include peels
      either alone or in combination with topical therapy. Lasers should rarely be used
      in the treatment of melasma and then only as third-line therapy in cases of
      melasma which is resistant to all other therapies. If applied, skin type must be
      taken into account. Irritation and sensitivity can be a concern in darker-skinned
      Hispanic patients and for this reason, the risk of post-inflammatory
      hyperpigmentation (PIH) following treatment should be considered.

PMID- 17176301
TI  - Guidelines for clinical trials in melasma. Pigmentation Disorders Academy.
AB  - There have been very few well-conducted trials in melasma and this makes the
      process of comparing treatment outcome between trials difficult. The Pigmentary
      Disorders Academy has examined the issues relating to clinical trials on melasma,
      and has proposed recommendations on how they should be conducted. This covers all
      aspects including correct diagnosis of the condition, evaluation of efficacy and
      safety outcome, and overall clinical trial design. It is anticipated that the
      establishment of accepted guidelines on the conduct of clinical trials in melasma
      will greatly assist the dermatological community.

PMID- 17176300
TI  - Validation of a melasma quality of life questionnaire for Brazilian Portuguese
      language: the MelasQoL-BP study and improvement of QoL of melasma patients after
      triple combination therapy.
AB  - BACKGROUND: Pigmentation disorders, such as melasma, greatly influence the
      quality of life (QoL) of affected individuals who usually consider the disorder
      to be more severe than the objective clinical scores. Several instruments have
      been successfully developed to evaluate QoL. However, they must be adapted to the
      target population in terms of language and cultural diversity. The first,
      specific QoL questionnaire for melasma (MelasQoL) was developed for English
      speaking patients. OBJECTIVES: To validate the Brazilian Portuguese version of
      the MelasQoL evaluation questionnaire for patients with melasma (MelasQoL-BP) and
      to assess the impact of treatment with a triple combination cream (hydroquinone,
      fluocinolone acetonide and tretinoin) on the QoL of patients with moderate-to
      severe melasma. METHODS AND RESULTS: Three hundred individuals from the five
      Brazilian geographic regions took part in this multicentre study. Their mean age
      was 42 years and skin phototype distribution was: type II 7.0% of patients, III
      23.7%, IV 42.7% and V 22.7%. Melasma Area and Severity Index (MASI), MelasQoL-BP
      and the short version of the QoL assessment instrument from the World Health
      Organization (WHOQOL-BREF) were used to assess melasma severity and QoL at
      baseline. MelasQoL-BP was previously translated and culturally adapted from the
      English version, with participation of the authors and according to the standards
      of the World Health Organization (WHO). From the original sample, we
      randomized150 volunteers to treat melasma and repeated the evaluation after 8
      weeks. The analysis of the MelasQoL-BP baseline answers demonstrated an important
      impact of the disease on skin appearance (65% of patients were bothered all the
      time or most of the time), frustration (55%), embarrassment (57%) and influence
      of the disease on interpersonal relationships (42%). Forty-three per cent of
      patients felt not attractive or even dirty due to their skin condition. MelasQoL
      BP results showed significant internal consistency (Cronbach's alpha coefficient
      0.919; P < 0.001) and good correlation with MASI scores. After treatment, the
      global assessment showed good or excellent results in 91.4% of the patients. The
      clinical outcome was not associated with the initial MASI score (P = 0.814; chi
      square), skin colour (P = 0.449; probability ratio) or skin pigmentation (P =
      0.814; chi-square). There was also a significant reduction on MelasQoL-BP scores
      (Wilcoxon test; P < 0.001) after treatment, with the mean +/- SD results shifting
      from 44.4 +/- 14.9 at baseline to 24.3 +/- 15.5 after treatment. The analysis of
      the MelasQoL-BP before and after treatment showed an important effect of the
      impact of treatment on a number of QoL measures. Of note, skin appearance (69.8
      vs. 10.1% of patients were bothered all the time or most of the time,
      respectively), frustration (59.7% vs. 12.2%, respectively), embarrassment (56%
      vs. 9.3%, respectively) and influence of the disease on interpersonal
      relationships (35.3% vs. 5.8%, respectively) were greatly improved. CONCLUSIONS:
      This study demonstrates that MelasQoL-BP is a valid instrument and can be used to
      evaluate the quality of life and response to melasma treatment in Brazilian
      patients. The triple combination treatment produced significant results,
      regarding both clinical severity and quality of life.

PMID- 17176303
TI  - Nursing and medical staff knowledge regarding the monitoring and management of
      accidental or exposure hypothermia in adult major trauma patients.
AB  - Recording a patient's vital signs is a basic requirement that in part informs
      clinical decision-making. Practice suggests that recording a trauma patient's
      temperature is occasionally overlooked in the emergency department. A staff
      survey was undertaken to gain an appreciation of knowledge and understanding of
      the issues that surround accidental or exposure hypothermia in trauma patients.
      Results demonstrate that nurses and doctors are unsure of how to define
      hypothermia and are not conversant with simple ways to prevent heat loss or
      rewarm patients. Complications from hypothermia such as coagulopathy and
      metabolic acidosis were seldom identified. Issues that limit staff recording
      temperature include patient access and acuity, lack of knowledge and confidence
      and access to temperature-measuring devices. These results emphasize the need for
      regular education. Implications for clinical practice were considered; an
      algorithm to guide staff on ways to improve the monitoring and management of
      temperature in trauma patients was developed. Opportunities for ongoing and
      further research were identified.

PMID- 17176304
TI  - Culturally diverse patient--nurse interactions on acute care wards.
AB  - The nurse-patient interaction is central to providing nursing care. This
      qualitative study explores nurses' and culturally diverse patients' experiences
      within nurse-patient relationships in acute care wards. Eight nurses and their
      respective patients volunteered to join the study and were interviewed. The three
      themes identified in relationships between nurses and culturally diverse patients
      were shared tension, perceived difference and held awareness. It is concluded
      from the study that relationships between nurses and culturally diverse patients
      in acute care wards during short episodes of hospitalization are not easy for
      nurses and need to receive deeper consideration as to how they can be developed
      more effectively. It is recommended that educational support be provided to
      develop more effective interactions between nurses and patients with research
      being carried out to investigate factors that can strengthen culturally diverse
      patient-nurse interactions in acute care settings.

PMID- 17176305
TI  - Searching for value: the influence of policy and reform on nurses' sense of value
      in long-term aged care in Australia.
AB  - Contemporary literature on long-term aged care focuses heavily on issues
      associated with the recruitment and retention of nursing staff, such as job
      satisfaction and attitudes towards caring for older people. This paper aims to
      highlight one aspect of a larger study of registered nurses' experiences in long
      term aged care in Australia and the influence that government policy and reform
      has in shaping that experience. This insight into aspects of nurses' everyday
      experience also contributes to a broader understanding of job satisfaction in
      long-term care. Findings from this study suggest that registered nurses
      experience tension in their search for value in their practice, which
      incorporates professional, political and social mediators of value and worth.
      These issues are discussed in relation to the impact of policy and reform on
      nurses' sense of value in long-term aged care and highlight the need for
      sensitive policy initiatives that support issues of value in nursing practice.

PMID- 17176306
TI  - Psychometric testing of a Norwegian version of the Premature Infant Pain Profile:
      an acute pain assessment tool. A clinical validation study.
AB  - As neonates are submitted to pain, assessing the pain is crucial in effective
      pain control. The Premature Infant Pain Profile, an acute measurement tool
      combining physiological, behavioural and contextual indicators, was translated
      into Norwegian and tested clinically. The purpose was to establish construct
      validity, interrater reliability and internal consistency. In addition, the
      effect of sucrose as pain analgesia was tested in neonates >or= 36 weeks of
      gestational age. In a known-groups comparisons design with repeated measures, 111
      consecutive neonates, preterm and term, were all observed at baseline, non-pain
      and pain event. Neonates in the neonatal unit received sucrose at pain event. A
      significant interaction effect of gestational age and events was found in the
      sucrose neonates. A significant interaction effect was detected from sucrose and
      event type for neonates from 36 weeks. The internal consistency of the six-item
      score was acceptable. A correlation coefficient of 0.89-0.97 was obtained for
      interrater reliability. The Norwegian version of the Premature Infant Pain
      Profile seems to be a reliable and valid instrument for pain assessment in
      neonates.

PMID- 17176307
TI  - Sexuality: the challenge to espoused holistic care.
AB  - Nurses, by virtue of the close relationship with patients, are in a unique
      position to promote sexual health and provide sexual health advice to people in
      their care. Although nurses espoused the ideals of person-centred and holistic
      care, evidence from research studies suggested that, for a number of reasons,
      nurses did not consciously and proactively engage with patients in relation to
      sexual concerns. In today health-care environment, where patients are seeking
      information about the impact of illness and treatments on their sexual function,
      nurses have a responsibility to proactively engage with patients' sexual health
      concerns in an informed and sensitive manner. The aim of this paper is to provide
      nurses with guidelines on how they might include this aspect of care within their
      everyday work.

PMID- 17176308
TI  - Opinions of ageing workers on relative importance of health promotion.
AB  - This study describes individual, workplace and occupational health-promoting
      factors, and their impacts for worker's health from the perspective of ageing
      Finnish workers. The pretested questionnaire was sent to 150 ageing workers, of
      whom 93 returned the form. Statistical analyses were performed using frequencies,
      means, Mann-Whitney U-test and Krushkal-Wallis test. Over 90% of respondents
      stated that health habits, individual arrangements in the workplace, good
      workplace atmosphere, access to health checks, counselling and nursing care all
      represented important factors for health promotion. Better health, work
      satisfaction and motivation of employees were the main factors impacting on
      health promotion. Ageing workers stated that health and safety organization and
      rehabilitation institutes were the most important copartners. Management must
      take a positive attitude towards ageing workers and make the necessary
      arrangements to support their well-being and this should be done in collaboration
      with occupational health professionals.

PMID- 17176309
TI  - Nurses' perceptions of multidisciplinary team work in acute health-care.
AB  - Multidisciplinary teamwork is viewed as one of the key processes through which
      care is managed in the British National Health Service, and yet is often viewed
      as one of the most problematic. Working in a multidisciplinary team requires many
      skills, which involves understanding not only one's own role but also the role of
      other professionals. The aim of this study was to explore nurses' perceptions of
      multidisciplinary teamwork in acute health-care. Nineteen nurses were interviewed
      using the critical incident approach to obtain their perceptions of
      multidisciplinary teamwork. Direct observation was conducted to record
      interactions between nurses and health-care professionals in multidisciplinary
      teams. In total, 14 meetings were attended in elder care and orthopaedics and
      seven in acute medicine. The findings of this study identified three barriers
      that hindered teamwork: (i) differing perceptions of teamwork; (ii) different
      levels of skills acquisitions to function as a team member; and (iii) the
      dominance of medical power that influenced interaction in teams. Thus, education
      establishments and nursing managers need to ensure that the acquisition of team
      playing skills is an integral part of continued professional development.

PMID- 17176310
TI  - The study of nursing documentation complexities.
AB  - This study aimed to explore complexities in nursing documentation and related
      factors. Nursing documentation has been one of the most important functions of
      nurses since the time of Florence Nightingale because it serves multiple and
      diverse purposes. Current health-care systems require that documentation ensures
      continuity of care, furnishes legal evidence of the process of care and supports
      evaluation of quality of patient care. However, nursing documentation has not
      served such objectives because of its complexities. This study explores nursing
      documentation complexities and related factors through both qualitative and
      quantitative methodologies. The study used multiple methods of inquiry: in-depth
      interviewing; participant observation; nominal group processing; focus group
      meetings; time and motion study of nursing activities; and auditing of
      completeness of nursing documentation. Complexities in nursing documentation
      include three aspects: disruption, incompleteness and inappropriate charting.
      Related factors that influenced documentation comprised: limited nurses'
      competence, motivation and confidence; ineffective nursing procedures; and
      inadequate nursing audit, supervision and staff development. These findings
      suggest that complexities in nursing documentation require extensive resolution
      and implicitly dictate strategies for nurse managers and nurses to take part in
      solving these complicated obstacles.

PMID- 17176311
TI  - Exploring the concept of 'information need'.
AB  - Identifying information needs is frequently espoused in textbooks, policy
      documents and reports of research studies; provision of health-care is also now
      described as 'needs-based', rather than 'service-based'. Yet, there is little
      understanding or clear definitions of this construct in the literature on the
      topic. The purpose of this paper is to explore the concept of information need,
      using concept analysis, with the aim of providing greater clarity. Rodgers'
      evolutionary approach to concept analysis was used to identify common attributes,
      antecedents and consequences, of the term information need. Information need
      emerged as a want or desire for information to be shared by professionals using
      appropriate communication skills. Information-seeking behaviour manifests in
      individuals as a response to a stimulus that is perceived as either a challenge
      or a threat. This attempt to provide a greater clarification of the term was
      prompted by the ubiquitous use of the term with little consistent definition. It
      is hoped that this conceptual clarification will guide further study in this
      area, particularly in relation to the subjective nature of contemporary
      information needs and its role in coping behaviours of individuals and groups.

PMID- 17176312
TI  - Transfusion medicine illustrated. Erythrophagocytosis in Epstein-Barr virus IgM
      mediated hemolytic anemia.

PMID- 17176313
TI  - Strategies for testing blood donors for West Nile virus.

PMID- 17176314
TI  - Transfusion-associated transmission of West Nile virus, United States 2003
      through 2005.
AB  - BACKGROUND: National blood donation screening for West Nile virus (WNV) started
      in June 2003, after the documentation of WNV transfusion-associated transmission
      (TAT) in 2002. STUDY DESIGN AND METHODS: Blood donations were screened with
      investigational nucleic acid amplification assays in minipool formats. Blood
      collection agencies (BCAs) reported screening results to state and local public
      health authorities. Donor test results and demographic information were forwarded
      to CDC via ArboNET, the national electronic arbovirus surveillance system. State
      health departments and BCAs also reported suspect WNV TATs to CDC, which
      investigated these reports to confirm WNV infection in blood transfusion
      recipients in the absence of likely mosquito exposure. RESULTS: During 2003 to
      2005, a total of 1,425 presumptive viremic donors were reported to CDC from 41
      states. Of 36 investigations of suspected WNV TAT in 2003, 6 cases were
      documented. Estimated viremia levels were available for donations implicated in
      four TAT cases; the median estimated viremia was 0.1 plaque-forming units (PFUs)
      per mL (range, 0.06-0.50 PFU/mL; 1 PFU equals approximately 400 copies/mL).
      CONCLUSIONS: National blood screening for WNV identified and removed more than
      1,400 potentially infectious blood donations in 2003 through 2005. Despite the
      success of screening in 2003, some residual WNV TAT risk remained due to
      donations containing very low levels of virus. Screening algorithms employing
      selected individual-donation testing were designed to address this residual risk
      and were fully implemented in 2004 and 2005. Continued vigilance for TAT will
      evaluate the effectiveness of these strategies.

PMID- 17176315
TI  - Sensitivity of hepatitis B virus DNA transcription-mediated amplification testing
      in hepatitis B surface antigen-positive blood donations.
AB  - BACKGROUND: The objective was to evaluate the performance of nucleic acid testing
      (NAT) in the detection of hepatitis B virus (HBV) infection in hepatitis B
      surface antigen (HBsAg)-positive blood donations. STUDY DESIGN AND METHODS: A
      total of 253 HBsAg- and anti-hepatitis B core antigen (HBc)-positive samples (50
      hepatitis B e antigen [HBeAg]-positive and 203 anti-HBe-positive) from blood
      donations collected in France were studied. The samples were investigated with a
      blood screening assay (Procleix Ultrio, Chiron/Gen-Probe) in minipool (MP; x8)
      and in individual-donation (ID) testing. All nonreactive samples were retested
      once, and nonreactive MP samples were assayed for viral load (VL). RESULTS: All
      50 HBeAg-positive samples were reactive in MP-NAT and ID-NAT. Of the 203 anti-HBe
      positive donations, 80.3 percent were MP- and ID-reactive, 17.2 percent were MP
      nonreactive and ID-reactive, and 2.5 percent were nonreactive in ID-NAT. Overall
      the sensitivity of ID-NAT was 98 percent versus 84 percent for MP-NAT. After
      retesting, 16 of the 35 MP-nonreactive and/or ID-reactive donations became MP
      reactive and 2 of the ID-nonreactive donations became NAT-reactive. The capacity
      of Procleix Ultrio to detect HBV DNA was not related to HBsAg subtype, but
      correlated with the VL: the mean VL in the group of MP-nonreactive samples was
      1,420 copies per mL vs. 17,000 copies per mL in the group of 40 MP-reactive
      samples. CONCLUSION: These results demonstrate that HBV-NAT in ID format is far
      more effective in detecting viremia in chronic HBsAg carriers than in MP-NAT. The
      sensitivity of the NAT assay needs to be improved to be considered for replacing
      the current HBsAg assays, especially when anti-HBc testing is not performed.

PMID- 17176316
TI  - A sealed and unbreached system for purification, stimulation, and expansion of
      cytomegalovirus-specific human CD4 and CD8 T lymphocytes.
AB  - BACKGROUND: Recent clinical trials have demonstrated the efficacy of adoptive
      cellular therapy with virus-specific lymphocytes in patients with defective
      cellular immune responses. Immunoreconstitution has become a challenge for
      cellular immunology and for transfusion medicine. In fact, both expertises are
      required to provide effective and safe cellular products. Because of in vitro
      manipulation, T-lymphocyte cultures are at risk of contamination even under good
      manufacturing procedure (GMP) conditions. STUDY DESIGN AND METHODS: To further
      improve the quality of these GMP cellular products, a procedure was designed for
      purification, stimulation, and expansion of antigen-specific CD4 and CD8 T
      lymphocytes in a sealed, unbreached system. Leukopacks from the blood bank that
      fulfill the requirements of a GMP product were the starting material. Gradient
      separation and washing were performed in bags with sterile connecting devices on
      the bench-top, as well as addition of ingredients (antigen, interleukin-2) or
      transfer to larger bags. RESULTS: The method is described in detail, and it is
      shown that increase in number of cytomegalovirus-specific CD4 or CD8 T
      lymphocytes was similar to procedures based on open culture systems. Cell
      expansion after 4 weeks ranged from 800- to 2400-fold for CD4 lymphocytes and 300
      to 900-fold for CD8 lymphocytes. Antigen specificity and loss of alloreactivity
      were demonstrated on the expanded cells with proliferation, intracytoplasmic
      interferon gamma-gamma staining, cytolytic activity, and pentamer binding.
      CONCLUSION: This procedure can be applied to improve sterility under GMP
      conditions when T-cell lines are generated for adoptive immunotherapy and may
      increase biosafety for the staff when cell lines are generated from subjects
      infected with dangerous pathogens.

PMID- 17176317
TI  - Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from
      a large cord blood bank.
AB  - BACKGROUND: Umbilical cord blood is a useful stem cell source for some patients.
      The American Red Cross Cord Blood Program was established as a national network
      of cord blood banks. Nine thousand cord blood units were cryopreserved for
      transplant use. STUDY DESIGN AND METHODS: This report summarizes the experience
      with the first 125 cord blood units that have been distributed for transplant for
      122 patients at 36 different transplant centers worldwide. Patients were treated
      with a variety of conditioning regimens. RESULTS: Most patients had acute
      myelogeneous leukemia (21%), genetic disorders (22%), or acute lymphoblastic
      leukemia (18%). The median age of the patients was 11 years with a range of 2
      months to 63 years. The patients ranged in size from 3 to 120 kg (median, 39 kg).
      The median number of days to neutrophil engraftment was 22, and the median number
      of days to platelet engraftment was 63. Thirty percent of patients experienced
      Grades III to IV acute graft-versus-host disease (GVHD). Survival at 1 year after
      transplant was 35 percent, with recurrent disease the major cause of death. In
      multivariate analysis, only age less than 18 years was a significant predictor
      for improved survival. Forty-two percent of patients were non-Caucasian.
      Engraftment, GVHD, survival, and disease-free survival were similar among
      Caucasian and non-Caucasian patients. CONCLUSION: Umbilical cord blood serves as
      a satisfactory stem cell source for a diverse group of pediatric and adult
      patients.

PMID- 17176318
TI  - Sterility testing of cell therapy products: parallel comparison of automated
      methods with a CFR-compliant method.
AB  - BACKGROUND: Automated blood culture systems are not FDA-approved for sterility
      testing of human cells, tissues, or cellular- or tissue-based products. It was
      previously demonstrated that BacT/ALERT (bioMerieux) and Bactec (Becton
      Dickinson) were superior to the manual CFR method described in the general
      biologics regulations, in rates of detection and time to detection of organisms
      seeded into mock mononuclear cell products with a variety of background media and
      antibiotics. In this study, the two automated systems were compared to the CFR
      method for sterility testing of actual cell therapy products manufactured in our
      facility. STUDY DESIGN AND METHODS: Over a 36-month period, in-process and final
      product samples from all cell therapy products manufactured in our facility were
      tested for sterility both by the CFR method and by either BacT/ALERT or Bactec.
      Products were categorized according to collection and processing variables for
      analysis of results. RESULTS: For 1617 samples of a broad range of cell therapy
      products, rates of true-positive tests were comparable for the automated and CFR
      methods (2.3% vs. 2.1%), but the CFR method had higher rates of false-positive
      results (7.3% vs. 0.2%). For automated systems, time to detection of organisms
      was equivalent to, or faster than, the CFR method. CONCLUSION: Compared to the
      CFR method, both BacT/ALERT and Bactec are more sensitive, faster in time to
      detection, less prone to false-positive results, and less labor-intensive. Both
      of these automated systems are suitable for sterility testing of cell therapy
      products after site-specific validation has been performed.

PMID- 17176319
TI  - A novel source of viable peripheral blood mononuclear cells from leukoreduction
      system chambers.
AB  - BACKGROUND: Buffy coats are becoming less available as a source of research-grade
      peripheral blood mononuclear cells (PBMNCs). Therefore, alternative sources of
      these cells were investigated. STUDY DESIGN AND METHODS: PBMNCs isolated from the
      cells retained in leukoreduction system chambers (LRSCs) and those eluted from
      white blood cell filters were compared. From LRSCs (1.88 +/- 0.40) x 10(9) PBMNCs
      (n = 13) versus (0.43 +/- 0.15) x 10(9) PBMNCs were isolated from leukofilter
      eluates (LFEs, n = 8; p < 0.0001). RESULTS: Cells from LRSCs and LFEs produced
      similar numbers of burst-forming unit-erythroid, colony-forming unit (CFU)
      granulocyte-macrophage, and CFU-granulocyte-erythrocyte-monocyte-macrophage
      megakaryocyte colonies. The percentages of cells positive for CD3, CD4, CD8,
      CD14, CD19, and CD56 in the PBMNCs isolated from LRSCs and LFEs were
      indistinguishable. Cells isolated from LRSCs expressed higher levels of CD69 and
      CD25 in reaction to staphylococcal enterotoxin B than the cells isolated from
      LFEs. The source of cells affected neither the yield and purity of
      immunomagnetically isolated CD3+ cells, CD14+ cells, and CD56+ cells nor the
      function of T cells, natural killer cells, and in vitro matured dendritic cells
      (DCs). DC yield from LRSC-derived CD14+ cells, however, was higher. CONCLUSION:
      LRSCs are a novel source of fully functional PBMNCs that can replace the more
      traditional sources of research-grade cellular products.

PMID- 17176320
TI  - Role of glycoprotein Ibalpha in phagocytosis of platelets by macrophages.
AB  - BACKGROUND: Platelet (PLT) storage at 0 to 4 degrees C suppresses bacterial
      multiplication, but induces clusters of glycoprotein (GP) Ibalpha that trigger
      their phagocytosis by macrophages and reduce their survival after transfusion. A
      method was sought that detects cold-induced changes in GPIbalpha involved in
      phagocytosis. STUDY DESIGN AND METHODS: Human PLTs were isolated and stored for
      up to 48 hours at 0 degrees C. Binding of a phycoerythrin (PE)-labeled antibody
      directed against amino acids (AA) 1-35 on GPIbalpha (AN51-PE) was compared with
      phagocytosis of PLTs by matured monocytic THP-1 cells, analyzed by fluorescence
      activated cell sorting. RESULTS: Freshly isolated PLTs were detected as a single
      population of AN51-PE-positive particles and showed less than 5 percent
      phagocytosis. Cold storage led to a decrease in AN51-PE binding and an increase
      in phagocytosis. N-Acetylglucosamine, known to interfere with macrophage
      recognition of GPIbalpha clusters, restored normal AN51-PE binding to cold-stored
      PLTs and suppressed phagocytosis. CONCLUSIONS: It is concluded that binding of an
      antibody against AA 1-35 on GPIbalpha reflects changes in GPIbalpha that make
      PLTs targets for phagocytosis by macrophages.

PMID- 17176321
TI  - A process for solvent/detergent treatment of plasma for transfusion at blood
      centers that use a disposable-bag system.
AB  - BACKGROUND: Solvent/detergent (S/D) inactivates enveloped viruses in plasma. The
      current technology requires a plasma fractionation facility and is applied to
      large plasma pools, which increases the cost and risks of exposure to S/D
      resistant pathogens and lowers the content of protein S and alpha2-antiplasmin.
      Two S/D treatment procedures for single donations or minipools of plasma have
      been developed with a single-use bag system. STUDY DESIGN AND METHODS: Frozen
      plasma samples were thawed and treated in disposable bags with either 2 percent
      tri(n-butyl)phosphate (TnBP) at 37 degrees C or 1 percent TnBP and 1 percent
      Triton X-45 at 31 degrees C for 4 hours. Plasma samples were extracted three
      times with 7.5 percent sterile castor oil to remove TnBP and Triton X-45. The
      TnBP-treated plasma samples were further subjected to a clarifying centrifugation
      (3800 x g, 30 min). Final plasma samples were dispensed into individual bags and
      frozen at -30 degrees C. Plasma quality was assessed at each step of the
      procedures. RESULTS: Both processes yielded greater than 90 percent mean recovery
      of coagulation factors (clottable fibrinogen, von Willebrand factor, and factors
      VIII, V, VII, IX, X, and XI), anticoagulants (protein C, protein S), protease
      inhibitors (antithrombin, alpha2-antiplasmin), total protein, albumin, and
      immunoglobulins. Global coagulation tests of the treated plasma samples were
      normal. Final TnBP and Triton X-45 content was less than 10 and 50 ppm,
      respectively. CONCLUSION: S/D treatment of plasma can be performed in a closed
      bag system under conditions that maintain plasma protein quality. The technology
      is simple, presents advantages over the industrial large-scale S/D plasma
      process, and could be performed in blood centers.

PMID- 17176322
TI  - International comparison of the technical efficiency of component preparation.
AB  - BACKGROUND: Under economical constraints, blood centers need to identify ways to
      improve their efficiency. Because there is little evidence regarding the
      technical efficiency of blood centers, international comparisons may be useful in
      identifying efficiency discrepancies and can reveal opportunities for enhancing
      efficiency, such as allocating resources more effectively. STUDY DESIGN AND
      METHODS: Data were collected for years 2000 through 2002 from 16 blood centers in
      10 European countries. Input variables included working hours, whole-blood (WB)
      collections, premises, and equipment, and the output variables were red blood
      cells and platelets (PLTs). A nonparametric method, data envelopment analysis
      (DEA), was used in the analyses of technical efficiency in blood component
      preparation departments. Efficiency scores were calculated with DEA linear
      programming techniques and evaluated for site characteristics that possibly
      affect efficiency, such as the production method of PLTs and the proportion of
      BCs (buffy coats) from WB and BC PLTs from all PLTs produced. RESULTS: With
      working hours and equipment as inputs, median technical efficiency was 60 percent
      (range, 41%-100%). Four departments were efficient (efficiency, > 90%), and 12
      were inefficient (range, 41-89). Efficiency remained roughly the same in 13
      departments through the 3-year study period and decreased in 3. Efficiency was
      mainly affected by staffing levels (working hours). Efficiency did not directly
      relate to production volume, method, or any other site characteristic.
      CONCLUSIONS: The major cause of inefficiency was excess staffing resulting from a
      suboptimal combination of manpower and production output levels. Further research
      is needed to manage factors affecting efficiency, such as the fluctuation of
      demand in production planning.

PMID- 17176323
TI  - Establishment of an immunoglobulin A-deficient blood donor registry with a simple
      in-house screening enzyme-linked immunosorbent assay.
AB  - BACKGROUND: Transfusion of blood products to immunoglobulin A (IgA)-deficient
      patients who have developed IgA antibodies can result in serious adverse
      reactions. To prepare compatible blood components for these patients, blood
      centers usually maintain a list of IgA-deficient blood donors. An in-house enzyme
      linked immunosorbent assay (ELISA) was used to identify new IgA-deficient blood
      donors. STUDY DESIGN AND METHODS: An in-house ELISA was used to screen blood
      samples. IgA-deficient samples, defined as an IgA level below 0.05 mg per dL,
      were sent to the American Red Cross for confirmatory testing. RESULTS: Seventy
      three confirmed IgA-deficient blood donors were identified among 38,759 screened
      blood donor samples (frequency, 1:531). IgA antibodies were found in 39 of these
      73 blood donors (53%), although only 9 donors had a history of adult IgA exposure
      (transfusion or pregnancy). CONCLUSIONS: With a simple in-house ELISA, 73 blood
      donors were identified as IgA-deficient. From this number, 34 donors, without
      detectable anti-IgA in their plasma, were added to our IgA-deficient blood donor
      panel to maximize the management of our inventory of IgA-deficient frozen blood
      components.

PMID- 17176324
TI  - Decreased immunorejection in unmatched blood transfusions by attachment of
      methoxypolyethylene glycol on human red blood cells and the effect on D antigen.
AB  - BACKGROUND: Pegylation of red blood cells (RBCs) has been the primary focus of
      research on the immunocamouflage of cell. The aim of this study was to
      demonstrate pegylation homogeneity, its shielding effect on D antigens, and its
      storage stability. In addition, methoxypolyethylene glycol (mPEG)-modified RBCs
      (mPEG-RBCs) were tested serologically against a panel of serum samples that was
      difficult to match to find a solution to the difficulty in matching. STUDY DESIGN
      AND METHODS: In this study, fluorescein-PEG and a confocal laser scanning
      microscope were used to monitor PEG attachment on RBC population and observe
      reaction homogeneity, the stability of mPEG combined with RBCs in vitro was
      evaluated by the RBC ghost agglutination test, the pegylation sites on membrane
      were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with
      two dye methods, and the effect of pegylation on D antigen was detected by
      immunoblotting techniques. Compatibility tests were carried out between 66 cases
      of serum with difficulty in blood matching and mPEG-camouflaged RBCs by use of
      four blood matching methods including direct agglutination, indirect antiglobulin
      test (IAT), microtyping gel cards (MTS), and the manual polybrene technique
      (MPT). RESULTS: The results indicated the homogeneity of pegylation, the absence
      of RhD protein in mPEG-modified D+ RBCs by Western blotting, and attachment of
      PEG to RBCs after 30 days of storage, while RBCs still remained antigenically
      silent. All pegylation RBCs showed a negative reaction with ABO-matched patients'
      serum samples by direct agglutination, IAT, and MTS, which indicated that
      pegylation RBCs and patients' serum samples were compatible. MPT was not suitable
      for detecting blood matching of mPEG-RBCs, because modification changed the RBCs'
      biophysical properties. CONCLUSION: In conclusion, mPEG-RBCs have acceptable in
      vitro properties and provide a useful solution to problems with clinical blood
      matching, although such masking leaves much to be desired.

PMID- 17176325
TI  - An easy RHD genotyping strategy for D- East Asian persons applied to Korean blood
      donors.
AB  - BACKGROUND: In East Asian populations RHD alleles are known to occur frequently
      among D- donors, requiring suitable genotyping strategies. The molecular basis of
      the "RHD(el)" allele previously reported in Taiwan to harbor a genomic 1013-bp
      deletion was questioned by several authors. STUDY DESIGN AND METHODS: The
      presence of the RHD gene was investigated in 126 random serologic D- blood donors
      from Gwangju, southwest Korea. Four donors who typed weakly positive for the D
      antigen were also analyzed. RH alleles were determined by polymerase chain
      reaction (PCR) with sequence-specific priming (PCR-SSP) or nucleotide sequencing.
      RESULTS: Seventy-five percent of the serologically D- samples lacked the RHD
      gene, 10 percent carried the hybrid RHD-CE(2-9)-D2 or RHD-CE(2-7)-D2 alleles, 13
      percent represented the RHD(K409K), and 2 percent were weak D type 15 and type
      17. Among the four donors typing weak D, two carried weak D type 15, one
      RHD(K409K), and one the novel weak D type 43. Critical molecular characteristics
      of RHD(K409K) and its population frequencies were indistinguishable to those
      reported for the RHDel allele. CONCLUSION: Korean RHD allele frequencies are
      comparable to Chinese and Japanese frequencies. It is concluded that the RHDel
      allele may actually not exist but is identical to RHD(K409K). A practical RHD
      genotyping strategy applicable to D- donors in all East Asian populations was
      devised. The strategy requires four PCR-SSP procedures only for RHD intron 4 and
      exon 7 as well as RHD(K409K) and non-RHD(K409K).

PMID- 17176327
TI  - Evaluation of prenatal RHD typing strategies on cell-free fetal DNA from maternal
      plasma.
AB  - BACKGROUND: The discovery of cell-free fetal DNA in maternal plasma led to the
      development of assays to predict the fetal D status with RHD-specific sequences.
      Few assays are designed in such a way that the fetus can be typed in RHDpsi
      mothers and that RHDpsi fetuses are correctly typed. Owing to the limited
      knowledge about the mechanism responsible for the presence of fetal DNA in
      maternal plasma, precautions in developing prenatal genotyping strategies must be
      made. STUDY DESIGN AND METHODS: Real-time quantitative (RQ)-polymerase chain
      reaction (PCR) assays were developed for prenatal diagnostic use with cell-free
      fetal DNA from maternal plasma. An RQ-PCR assay on RHD exon 5 (amplicon 361 bp),
      negative on RHDpsi, was developed with genomic DNA and evaluated with cell-free
      fetal DNA. A previously published RHD exon 5 RQ-PCR (amplicon 82 bp) was duplexed
      with an in-house developed RHD exon 7 RQ-PCR and evaluated with cell-free fetal
      DNA from pregnant D-RHDpsi+ women. RESULTS: The RHD exon 5 361 bp assay showed on
      cell-free plasma DNA from D- women carrying a D+ fetus, low amplification levels,
      resulting in high Ct values and false-negative results. Owing to fragmentation of
      cell-free plasma DNA, too few DNA stretches of sufficient length (> 360 bp) are
      present. The RHD exon 5 82 bp and exon 7 RQ-PCR duplex was evaluated with RHDpsi+
      cell-free plasma DNA and showed complete specificity and maximal sensitivity.
      CONCLUSION: Assays designed for prenatal genotyping should be developed and
      evaluated on cell-free plasma DNA. Prenatal RHD typing is accurate with the RHD
      exon 5 82 bp and exon 7 duplex strategy.

PMID- 17176326
TI  - New mutation in the platelet beta3-integrin gene: implication for the diagnosis
      of fetomaternal alloimmunization.
AB  - BACKGROUND: Fetal ventriculomegaly is a relatively common finding and
      fetomaternal alloimmune thrombocytopenia may be one of the causes. STUDY DESIGN
      AND METHODS: Such a case discovered at 21 weeks of gestation leading to platelet
      (PLT) immunologic testing is reported here. PLT genotyping was performed by
      polymerase chain reaction (PCR)-sequence-specific primers (SSPs) method and PCR
      restriction fragment length polymorphism (RFLP) analysis. Serologic investigation
      was done with the monoclonal antibody-specific immobilization of PLT antigens
      technique. RESULTS: The mother was found to be HPA-1b homozygous and the father
      HPA-1a homozygous with PCR-SSP, but the mother was found to be HPA-1 heterozygous
      by phenotyping. This result was confirmed by PCR-RFLP. Sequencing of the
      glycoprotein IIIa exon 3 revealed a heterozygous mutation 262T > C, which does
      not induce an amino acid change. It is localized in the sequence of the antisense
      primer of the HPA-1 PCR-SSP, inducing the sole amplification of the DNA copy
      bearing the HPA-1b allele. CONCLUSION: Even if such mutations are a rare event,
      PLT phenotyping is still of interest to avoid rare false PLT typing assignation,
      the unknown polymorphism being only discovered by such a combination of
      techniques.

PMID- 17176328
TI  - Identification of six new alleles at the FUT1 and FUT2 loci in ethnically diverse
      individuals with Bombay and Para-Bombay phenotypes.
AB  - BACKGROUND: The Bombay and para-Bombay phenotypes arise from mutations of the
      FUT1 gene that silence the gene or affect the efficiency of the encoded 2-alpha
      fucosyltransferase. Samples from seven individuals of different geographic
      backgrounds whose red blood cells had an apparent Bombay or para-Bombay phenotype
      were investigated. Among these, novel FUT1 and FUT2 alleles were identified.
      STUDY DESIGN AND METHODS: Standard serologic techniques were used. Genomic DNA
      was sequenced with primers that amplified the coding sequence of FUT1 and the
      related secretor gene, FUT2. Routine ABO genotyping analysis was performed.
      RESULTS: Five new FUT1 alleles were identified that silenced FUT1 or weakened
      alpha2FucT1 activity. These were 35C>T, 269G>T (Ala11Val, Gly89Val); 421A>G
      (Trp140Stop); 538C>T, 1089T>G (Gln180Stop, Ala363Ala); 689A>C (Gln230Pro); and
      917C>T (Thr305Ile). In addition, both homozygosity and heterozygosity for the
      previously reported mutation, 826C>T (Gln276Stop), were observed. Four of seven
      samples were homozygous for the silencing mutation 428A in FUT2. One new FUT2
      allele was identified: 278C>T, 357C>T (Ala93Val, Asn119Asn). CONCLUSIONS: These
      results add to the growing database of apparently sporadic and random mutations
      in the FUT1 gene and confirm previous reports regarding the lack of ethnic bias.
      In contrast, our data reinforce the apparent maintenance of the common
      nonsecretor FUT2 alleles in the population.

PMID- 17176329
TI  - In-frame triplet deletions in RHD alter the D antigen phenotype.
AB  - BACKGROUND: The deletion of three adjacent nucleotides in an exon may cause the
      lack of a single amino acid, while the protein sequence remains otherwise
      unchanged. Only one such in-frame deletion is known in the two RH genes,
      represented by the RHCE allele ceBP expressing a "very weak e antigen." STUDY
      DESIGN AND METHODS: Blood donor samples were recognized because of discrepant
      results of D phenotyping. Six samples came from Switzerland and one from Northern
      Germany. The molecular structures were determined by genomic DNA nucleotide
      sequencing of RHD. RESULTS: Two different variant D antigens were explained by
      RHD alleles harboring one in-frame triplet deletion each. Both single-amino-acid
      deletions led to partial D phenotypes with weak D antigen expression. Because of
      their D category V-like phenotypes, the RHD(Arg229del) allele was dubbed DVL-1
      and the RHD(Lys235del) allele DVL-2. These in-frame triplet deletions are located
      in GAGAA or GAAGA repeats of the RHD exon 5. CONCLUSION: Partial D may be caused
      by a single-amino-acid deletion in RhD. The altered RhD protein segments in DVL
      types are adjacent to the extracellular loop 4, which constitutes one of the most
      immunogenic parts of the D antigen. These RhD protein segments are also altered
      in all DV, which may explain the similarity in phenotype. At the nucleotide
      level, the triplet deletions may have resulted from replication slippage. A total
      of nine amino acid positions in an Rhesus protein may be affected by this
      mechanism.

PMID- 17176330
TI  - The restricted use of IGHV3 superspecies genes in anti-Rh is not limited to
      hyperimmunized anti-D donors.
AB  - BACKGROUND: Antibodies produced against the D antigen make use of IGHV genes
      restricted to the IGHV3 superfamily. These findings are based on the IGHV gene
      analysis in anti-D-producing B cells from hyperimmunized donors, however, and
      therefore the restriction might be due to the hyperimmunization. In this study
      the IGHV gene usage of anti-Rh-producing B cells in a woman who was immunized in
      the last trimester of her pregnancy was analyzed. STUDY DESIGN AND METHODS:
      Serologic analysis was performed by absorption and elution. Antibody-dependent
      cellular cytotoxicity (ADCC) of the different anti-Rh was determined. A phage
      display library was constructed from 2.2 x 10(6) isolated B cells and pannings
      were performed with red cells of the r'r, R1R1, and R2R2 phenotype. RESULTS: A
      plasma sample of the immunized person showed high levels of both anti-D and anti
      G and low levels of anti-C. Anti-D and anti-G contributed equally strong to the
      ADCC whereas anti-C did not. Eighteen anti-D-, 5 anti-G-, and 1 anti-C-specific
      phage clones were found, of which 16, 2, and 1 used the IGHV3s genes,
      respectively. CONCLUSION: For the first time a restriction to the IGHV3s genes in
      anti-D in a naturally immunized pregnant woman is shown. Moreover, the use of
      IGHV3s genes appears to be present in anti-C and anti-G as well. Therefore, it is
      concluded that restricted IGHV3s gene usage in anti-D is not due to
      hyperimmunization but due to characteristics of the Rh antigens and the intrinsic
      binding capacities of IGHV3s genes, supporting the common Rh footprint
      hypothesis.

PMID- 17176331
TI  - The Canadian donor health assessment questionnaire: can it be improved?
AB  - BACKGROUND: The donor health assessment questionnaire (DHAQ) plays an important
      role in ensuring blood safety. The Canadian DHAQ has been developed over many
      years on an ad hoc basis and has never been evaluated in light of cognitive
      science principles. In addition, donor attitudes about its mode of administration
      have not been assessed. STUDY DESIGN AND METHODS: Between May and August 2005, a
      total of 456 donors participated in the study by completing the DHAQ, followed by
      a short, scripted interview assessing recall (as an indicator of attention to the
      questions) of 17 specific items queried on the DHAQ and attitudes toward
      interviewer or self-administration of the DHAQ. RESULTS: Overall, 7.5 percent of
      donors were able to correctly identify all 17 items. Recall was best for
      questions asked as individual items (87%-99%) and decreased substantially for
      items that are part of a list (55%-91%). Position effects were demonstrated, with
      items at the end of a list being the most frequently forgotten. Twenty percent of
      repeat donors favored the current practice of interviewer administration of high
      risk questions, whereas 80 percent were neutral or favored self-administration.
      CONCLUSION: The current format of the Canadian DHAQ is not optimal for donor
      attention to specific questions asked as part of a list. The majority of repeat
      donors are ready for a change in the method of administration of the DHAQ.
      Studies on donor recall may help guide evidence-based changes to the DHAQ.

PMID- 17176332
TI  - Selection of whole-blood donors for hemoglobin testing by use of historical
      hemoglobin values.
AB  - BACKGROUND: Usually, a predonation hemoglobin (Hb) measurement must precede blood
      donation. Hb values of a donor's previous donation might be used for selecting a
      subgroup in which predonation Hb measurements are unnecessary. STUDY DESIGN AND
      METHODS: Only donors with historical Hb values below 129 or 139 g per L for
      female and male donors, respectively, underwent venous Hb measurement before
      phlebotomy with an automated hematology analyzer. All other donor phlebotomies
      were collected without initial Hb testing. Hb values from diversion samples from
      81,913 consecutive donors between May 2003 and November 2005 were subsequently
      analyzed as representing their present values. Donors were grouped according to
      interdonation intervals of less than 6, 6 to 11, 12 to 23, and 24 months or more.
      RESULTS: The arithmetic mean deviation between historical and present Hb values
      was between -0.3 and +1.8 g per L for each group (mean deviation, 5.2-6.7 g/L).
      Not testing selected donors spared 77.7 percent from a prephlebotomy Hb
      measurement and showed a specificity of 29 percent. Sensitivities for detection
      of donors below Hb limits (between 56% and 67% for the different subgroups) and
      donors with Hb values below 110 g per L (82%-88%) were at least comparable to
      capillary Hb screening. A total of 4.8 percent of donors were phlebotomized with
      values below 125 and 135 g per L, whereas only 0.016 percent of donors were bled
      despite Hb levels below 110 g per L. CONCLUSION: Selecting donors for a current
      Hb measurement based upon their last whole-blood predonation Hb value is a useful
      method, even after prolonged interdonation intervals.

PMID- 17176333
TI  - Hematomas in multicomponent apheresis: searching for related factors.
AB  - BACKGROUND: The objective of this study was to identify donation variables that
      could be related to the development of hematoma during multicomponent apheresis
      collections (MACs). STUDY DESIGN AND METHODS: This is an observational
      retrospective study where 1375 donors donated 5177 MACs during a 2-year period
      with two different machines (Amicus Crescendo [AC], Baxter Healthcare Corp.; and
      Trima Accel [TA], Gambro BCT). Variable data were recorded prospectively. In the
      multiple logistic regression analysis, generalized estimating equations were used
      with an exchangeable correlation matrix to take into account the nonindependence
      of several measurements from the same donor. RESULTS: During the study period,
      170 procedures failed due to hematoma (3.3%). Several variables were related to
      hematoma development in the adjusted model: operator experience (less than 500
      procedures supervised vs. more; odds ratio [OR], 1.66; 95% confidence interval
      [CI], 1.19-2.31), previous apheresis donations (first time vs. more than 16
      donations; OR, 2.87; 95% CI, 1.52-5.45), vein canalized (basilic vs. intermediate
      antebrachial or cephalic; OR, 1.42; 95% CI, 1.04-1.94), diastolic blood pressure
      (units divided by 10 mmHg; OR, 0.79; 95% CI, 0.66-0.94), and type of machine used
      (TA high return limit configuration [RLC] setting configuration vs. AC; OR, 1.94;
      95% CI, 1.27-2.96; TA low RLC setting configuration vs. AC; OR, 1.24; 95% CI,
      0.83-1.84). CONCLUSIONS: Our study suggests that hematoma in MAC is not a random
      event. Appropriate machine configuration in the TA could reduce the hematoma rate
      to a level comparable with that of the AC. Operator training and donor blood
      pressure are also interesting variables for study because these could be modified
      to reduce the hematoma rate.

PMID- 17176334
TI  - Transfusion trigger trial for functional outcomes in cardiovascular patients
      undergoing surgical hip fracture repair (FOCUS).

PMID- 17176335
TI  - Aprotinin and renal risk in cardiac surgery.

PMID- 17176336
TI  - Aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery.

PMID- 17176338
TI  - Red blood cell and platelet transfusions in the treatment of anemic
      thrombocytopenic patients.

PMID- 17176340
TI  - Editorial: A small step for WHO, a big step for cholera control.

PMID- 17176341
TI  - Comparative evaluation of freeze-dried and liquid antigens in the direct
      agglutination test for serodiagnosis of visceral leishmaniasis (ITMA-DAT/VL).
AB  - OBJECTIVE: The direct agglutination test (DAT) for visceral leishmaniasis (VL)
      with liquid (LQ) antigen is known to be only moderately reproducible because of
      inter-observer and batch-to-batch variability as well as its sensitivity to
      temperature and shaking during transport. We evaluated a DAT with freeze-dried
      (FD) antigen and compared it with the LQ antigen version. METHODS: Blood samples
      of clinical VL suspects and healthy endemic controls were collected in Sudan,
      Nepal and India. Both test versions were performed in duplicate in the respective
      countries and in the reference laboratory. Interbatch variability and stability
      tests were conducted and agreement was examined within and between centres on a
      dichotomic scale by Cohen's kappa as well as on a continuous scale through Bland
      Altman plots. RESULTS: The FD antigen remains fully active even after storage at
      45 degrees C for 24 months. Using a cut-off titre of 1:6400, the agreement
      between the FD and the LQ formats was excellent. CONCLUSION: The major advantages
      of FD antigen are its better stability at higher temperatures and its longer
      shelf life, which make it much more suitable than the LQ version for use in the
      field.

PMID- 17176342
TI  - Leishmania and sand flies: proximity to woodland as a risk factor for infection
      in a rural focus of visceral leishmaniasis in west central Venezuela.
AB  - OBJECTIVE: To relate entomological, epidemiological and geographical data to
      understand the transmission dynamics of visceral leishmaniasis (VL) in a closed
      focus in western Venezuela. METHODS: Spatial and temporal patterns of Lutzomyia
      pseudolongipalpis, the most prevalent phlebotomine sand fly species (99.7%), were
      studied in El Brasilar, Curarigua, Lara State, Venezuela, a small rural community
      of 20 dwellings and 118 inhabitants. The sand fly population was monitored using
      Centers for Disease Control light traps monthly throughout 1 year in the domestic
      and sylvatic habitats and for 3 months in all inhabited houses. RESULTS: Temporal
      variation followed the yearly bimodal pattern of precipitation with the highest
      population densities in April and December. Infection with flagellates suggestive
      of Leishmania spp. was detected in 0.01% of 10,026 dissected females of L.
      pseudolongipalpis, which proved to be highly endophilic. Prevalence of Leishmania
      infection in people, as measured by the leishmanin skin test, was correlated with
      distance of the houses from the woodland and with sand fly abundance. A logistic
      regression model showed that for people who live in the village, the proximity to
      the woodland (linear) should be considered a risk factor for Leishmania infection
      (binary) (z = -2.02, P = 0.04, OR = 0.98, 95% CI = 0.97-0.99). This was
      consistent with the association between the proportion of VL infection and the
      log of sand fly abundance, which was negatively correlated with distance from the
      woodland. CONCLUSION: We discuss strategies that might be useful in controlling
      VL transmission in this endemic focus.

PMID- 17176343
TI  - Visceral leishmaniasis in southeastern Nepal: a cross-sectional survey on
      Leishmania donovani infection and its risk factors.
AB  - OBJECTIVE: To document the frequency of Leishmania donovani infection at
      community level in a highly endemic region in southeastern Nepal, and to assess
      socioeconomic and environmental risk factors. METHODS: A random cross-sectional
      population survey was held in two visceral leishmaniasis (VL) foci in Morang
      District in April to May 2003, enrolling individuals 2 years or older and
      residing in the endemic area for at least 12 months. Leishmania infection was
      defined as a direct agglutination test (DAT) titre equal to or higher than
      1:3200. Risk factors were identified by logistic regression. RESULTS: The direct
      agglutination test was positive in 7.5% (95% CI: 5.1-10.8) and the leishmanin
      skin test (LST) in 13.2% (95% CI: 9.9-17.2) of the 373 study participants. No
      case of current kala-azar was found, but 5.1 % (95% CI: 3.1-7.8) reported having
      suffered from VL. Independent risk factors for Leishmania infection were
      proximity of the house to ponds [odds ratio (OR) 3.7, 95% CI: 1.6-8.5], family
      size (OR 4.4, 95% CI: 1.6-12.6), age > or =15 years (OR 5.5, 95% CI: 1.2-25.0)
      and house constructed in mud (OR 3.0, 95% CI: 1.1-7.6). Bednets, not impregnated
      and in poor condition, were used by 95.2% (95% CI: 92.3-97.0) of the population,
      but did not show any protective effect. CONCLUSION: This study shows that there
      is a serious problem of transmission of VL in this area of Nepal. The risk
      factors identified are linked with the socioeconomic level and the environment.
      The population would benefit from a community intervention to improve the
      environmental and housing conditions in the villages.

PMID- 17176344
TI  - Efficacy of artemether-lumefantrine for the treatment of uncomplicated falciparum
      malaria in northwest Cambodia.
AB  - OBJECTIVE: To determine the efficacy of artemether-lumefantrine malaria
      treatment, as an alternative to artesunate + mefloquine, which is becoming
      ineffective in some areas of the Thai-Cambodian border. METHODS: Two studies were
      conducted to monitor the efficacy of artemether-lumefantrine in Sampov Lun
      referral hospital, Battambang Province, in 2002 and 2003, and one study was
      conducted to assess the efficacy of mefloquine + artesunate in 2003 for
      comparison. The studies were performed according to the WHO standardized protocol
      with a follow-up of 28 days. The therapeutic efficacy tests were complemented
      with in vitro tests and in 2003, with the measurement of lumefantrine plasma
      concentration at day 7 for the patients treated with artemether-lumefantrine.
      RESULTS: A total of 190 patients were included: 55 were treated with artemether
      lumefantrine in 2002 (AL2002), 80 with artemether-lumefantrine and food
      supplementation in 2003 (AL2003) and 55 with artesunate + mefloquine in 2003
      (AM2003). With the per-protocol analysis, the cure rate was 71.1% in study
      AL2002, 86.5% in study AL2003 and 92.4% in study AM2003. All the data were PCR
      corrected. The artemether-lumefantrine cure rate was unexpectedly low in 2002,
      but it increased with food supplementation in 2003. There was a significant
      difference (P = 0.02) in lumefantrine plasma concentrations between adequate
      clinical and parasitological responses and treatment failure cases. In vitro
      susceptibility to lumefantrine was reduced for isolates sampled from patients
      presenting with treatment failure, but the difference was not statistically
      different from isolates sampled from patients who were successfully treated.
      CONCLUSION: Treatment failure cases of artemether-lumefantrine are most probably
      because of low levels of lumefantrine blood concentration. Further investigations
      are necessary to determine whether resistance of Plasmodium falciparum isolates
      to lumefantrine is present in the region.

PMID- 17176346
TI  - Prevalence and risk factors of intestinal parasites in Cuban children.
AB  - OBJECTIVES: To determine the prevalence of intestinal parasite infections and
      their risk factors in children in urban and rural settings in two Cuban
      municipalities. METHODS: A total of 1320 Cuban schoolchildren aged 4-14 were
      tested by stool examination for intestinal parasite infections and evaluated by
      parental questionnaire for a number of common environmental, sanitary,
      socioeconomic and behavioural risk factors. Multivariate regression was applied
      to examine the relationship between the respective parasite infections and the
      risk factors. RESULTS: Prevalences of intestinal parasite infections were 58% in
      Fomento and 45% in San Juan y Martinez; for helminth infections, these were 18%
      and 24% and for protozoa infections, 50% and 29%, respectively. Helminth
      infections were associated with high parental education (maternal: OR 0.68, CI
      0.50-0.93; paternal: OR 0.71, CI 0.52-0.96), absence of toilet (OR 1.57, CI 1.12
      2.19), consumption of water from a well or river (OR 0.56, CI 0.41-0.77) and
      eating unpeeled/unwashed fruit (OR 1.37, CI 1.01-1.87); protozoa infections were
      only associated with high maternal education (OR 0.72, CI 0.57-0.91).
      CONCLUSIONS: Paediatric intestinal parasite infections are still prevalent in
      certain areas in Cuba and associated with a number of common environmental,
      socioeconomic and sanitary risk factors.

PMID- 17176345
TI  - Amodiaquine resistance is not related to rare findings of pfmdr1 gene
      amplifications in Kenya.
AB  - OBJECTIVES: Many countries are now adopting artemisinin-based combination therapy
      (ACT) for treatment of Plasmodium falciparum malaria. In multi-drug resistant
      areas in South East Asia amplifications of the pfmdr1 gene are frequent and
      tentatively associated with reduced susceptibility to the common quinoline
      partner drugs mefloquine and lumefantrine. In Africa where amodiaquine is one of
      the favoured quinoline partner drugs in ACT, studies on multi-drug resistance
      associated pfmdr1 gene amplifications are urgent. Our aim was to determine the
      current prevalence of pfmdr1 gene amplifications and a possible association
      between pfmdr1 gene copy number and amodiaquine treatment outcome in Kenya.
      METHODS: Seventy-two children with Plasmodium falciparum infection in Kenya were
      treated with amodiaquine monotherapy and followed for 21 days. Possible
      amplification of the pfmdr1 gene was assessed from blood-spotted filterpaper by
      TaqMan probe based real-time polymerase chain reaction. RESULTS: The recrudescent
      rate was 14 of 72 (19%). All children had single pfmdr1 copy infections, with the
      exception of one child who had an infection with two pfmdr1 copies. This child
      had an adequate treatment response. CONCLUSION: Pfmdr1 amplifications do exist in
      Kenya but at a very low frequency. Yet, the substantial number of children with
      recrudescent infections implies that amodiaquine resistance is not related to
      pfmdr1 gene amplifications in Kenya.

PMID- 17176347
TI  - Association between intestinal parasitic infections and type of sanitation system
      in rural El Salvador.
AB  - OBJECTIVE: To identify demographic, behavioural and environmental determinants of
      intestinal parasitic infection, evaluate the impact of a variety of dry
      sanitation systems on intestinal parasitic infection, and evaluate the safety of
      using stored biosolids in agriculture in order to guide future sanitation
      interventions in rural areas of El Salvador. METHODS: Interviews were conducted
      with 109 households in eight communities where double-vaulted and solar urine
      diverting desiccating latrines, pit latrines or no latrines were used. Faecal
      samples from 499 individuals were tested for enteric helminths and protozoa.
      RESULTS: Users of solar desiccating latrines had the lowest prevalence of enteric
      parasite infection. Double-vault, urine-diverting desiccating latrines
      effectively reduced the transmission of some pathogens, but may not achieve the
      conditions sufficient for the complete destruction of the more environmentally
      persistent pathogens, Ascaris lumbricoides and Trichuris trichiura. Contact with
      inadequately treated latrine biosolids was associated with an increased risk of
      Ascaris infection. CONCLUSIONS: Solar latrines were associated with the overall
      lowest prevalence of enteric parasitic infections. Members of households where
      latrine biosolids were used in agriculture had a higher prevalence of infection
      than those where biosolids were buried. We therefore recommend the promotion of
      solar latrines in rural areas of El Salvador over other dry sanitation systems,
      and recommend that stored biosolids not be used in agriculture.

PMID- 17176348
TI  - Estimates of intraclass correlation coefficient and design effect for surveys and
      cluster randomized trials on injection use in Pakistan and developing countries.
AB  - BACKGROUND: To assess injection practices and to test interventions aimed at
      reducing unsafe injections in developing countries, cluster surveys and cluster
      randomized trials are needed. The design of cluster-based studies requires
      estimates of intraclass correlation coefficients that have to be obtained from
      previous studies. This study presents such estimates. METHODS: Data were derived
      from a cross-sectional study of injection use and health seeking in Pakistan that
      used 34 clusters to select 1150 study subjects aged > or =3 months. We analysed
      variance to separate its components. RESULTS: Most of intraclass correlation
      coefficients were in the range of 0.01-0.05. For proportion of injections
      received during last 3 months, mean number of injections received and health
      seeking during the past 3 months the intraclass correlation coefficients were
      0.02, 0.04 and 0.02, respectively. CONCLUSION: These estimates can be useful in
      designing cluster surveys and cluster randomized trials for injection safety in
      Pakistan and other developing countries.

PMID- 17176349
TI  - Rates and causes of child mortality in an area of high HIV prevalence in rural
      South Africa.
AB  - OBJECTIVE: To determine child mortality rates in a rural area of South Africa
      with high HIV prevalence. METHODS: A community-based survey was conducted between
      1 January 2000 and 31 December 2002 on deaths in children under the age of 15
      years. Children were followed up through four monthly home visits. Cause of death
      was ascertained by verbal autopsy. Rates were calculated using Poisson
      regression. RESULTS: Mortality ratios were 59.6 deaths per 1000 live births for
      infants and 97.1 for children under 5 years of age. Infant and under-5 mortality
      rates were, respectively, 67.5 and 21.1 deaths per 1000 person-years. HIV/AIDS
      was attributed to 41% of deaths in the under-5 age group, with a mortality rate
      of 8.6 per 1000 person-years. Lower respiratory infections caused an estimated
      24.9 deaths per 1000 person-years in children under 1 year of age. CONCLUSIONS:
      In rural South Africa, infant and child mortality levels are high, with HIV/AIDS
      estimated as the single largest cause of death. Interventions to reduce child
      mortality are required urgently.

PMID- 17176350
TI  - Micronutrient interventions and HIV infection: a review of current evidence.
AB  - OBJECTIVE: To review the current evidence on the role of micronutrient
      supplementation in HIV transmission and progression. METHOD: Literature review.
      RESULTS: The importance of micronutrients in the prevention and treatment of
      childhood infections is well known, and evidence is emerging that micronutrient
      interventions may also affect HIV transmission and progression. CONCLUSION:
      Interventions to improve micronutrient intake and status could contribute to a
      reduction in the magnitude and impact of the global HIV epidemic. However, more
      research is needed before specific recommendations can be made.

PMID- 17176351
TI  - Uncovering and responding to needs for sexual and reproductive health care among
      poor urban female adolescents in Nicaragua.
AB  - BACKGROUND: To meet the needs of female adolescents from low-income urban areas
      for sexual and reproductive health (SRH) care, vouchers providing free-of-charge
      access to SRH care at 19 primary care clinics were distributed in Managua,
      Nicaragua. These vouchers substantially increased the use of services,
      demonstrating that many adolescents are willing to use such services, if readily
      accessible. The voucher redemption made it possible to identify the nature of
      existing, but largely unmet, needs for SRH care. METHOD: The medical files from
      3301 consultations with female adolescents were analysed using descriptive
      statistical methods and multiple logistic regression. RESULTS: Female adolescents
      presented SRH problems that merited medical attention. The mean number of
      problems presented was 1.5 per consultation: 34% of the vouchers were used for
      contraceptives, 31% for complaints related to sexually transmitted infection
      (STI) or reproductive tract infection (RTI), 28% for advice/counselling, 28% for
      antenatal check-up and 18% for pregnancy testing. A new category of health care
      users emerged: sexually active girls who were neither pregnant nor mothers and
      who sought contraceptives or STI/RTI treatment. Contraceptive use doubled among
      the sexually active non-pregnant voucher redeemers. Consultation with a female
      doctor younger than 36 years was associated with a higher chance of having
      contraceptives prescribed. CONCLUSION: Accessible and appropriate SRH care has
      the potential to make an important contribution to the increased contraceptive
      use, decreased risk of unwanted teenage pregnancies and decreased prevalence of
      STIs/RTIs among underserved adolescents. Once adolescents access the services,
      providers have a crucial role in ensuring current and continuing needs are met.

PMID- 17176352
TI  - Knowing a medical doctor is associated with reduced mortality among sick children
      consulting a paediatric ward in Guinea-Bissau, West Africa.
AB  - BACKGROUND: To examine equity in access to public health services in Guinea
      Bissau. METHODS: The study was conducted in 2000-2001 at the emergency clinic of
      the only paediatric ward in Bissau. Mothers of all children from the study area
      were interviewed about previous care seeking and relations with anybody working
      in the health sector. All management actions in the emergency clinic were
      registered. In-hospital and subsequent community mortality was ascertained
      through community surveillance. The measured outcome was mortality risk within 30
      days of first consultation. RESULTS: We followed 1572 children with a first
      consultation. Of these, 8.2% died within 30 days. Acquaintance with a physician
      reduced 30-day mortality risk by 48% (95% CI: 18-66). The effect was strongest
      among post-neonatal children (54%; 95% CI: 18-74). Mortality within 30 days of
      consultation was also independently predicted by consultation after 7 PM, nurse
      team on duty, day of week and young mother. In a multivariate model,
      socioeconomic status and school education were not associated with 30-day
      mortality when acquaintance with a medical doctor was taken into account.
      CONCLUSION: Favouritism may be a significant factor for quality of care and child
      mortality in developing countries. Interventions to improve hospital and health
      worker performance should be given high priority.

PMID- 17176353
TI  - Rift Valley fever in West Africa: the role of space in endemicity.
AB  - Rift Valley fever is an endemic vector-borne disease in West Africa, which mainly
      affects domestic ruminants and occasionally humans. The aetiological mechanisms
      of its endemicity remain under debate. We used a simple spatially explicit model
      to assess the possibility of endemicity without wild animals providing a
      permanent virus reservoir. Our model takes into account the vertical transmission
      in some mosquito species, the rainfall-driven emergence of their eggs and local
      and distant contacts because of herd migration. Endemicity without such a
      permanent virus reservoir would be impossible in a single site except when there
      is a strictly periodic rainfall pattern; but it would be possible when there are
      herd movements and sufficient inter-site variability in rainfall, which drives
      mosquito emergence.

PMID- 17176354
TI  - Learning from health system reforms: lessons from Burkina Faso.
AB  - OBJECTIVES: Burkina Faso has implemented a macroeconomic adjustment programme
      (MAP) along with an ambitious reform of the health care system. Our aim was (1)
      to verify whether MAPs led to a reduction in health resources, and (2) to analyze
      the consequences of health policies implemented. METHOD: Cross-sectional and
      retrospective study, spanning the years 1983-2003. The macro aspect is based upon
      documents from national and international sources, a database of secondary
      socioeconomic data, and interviews of key informants working in upper management.
      Household and health facility surveys were conducted in three regions covering 53
      communities. RESULTS: Within the reforms, the health sector benefited from an
      important flow of resources. There were significant increases in public
      expenditures, health care staff, the number of primary care facilities and the
      availability of generic drugs. However, health facilities in the public sector
      remain underused and major inequities subsist. Access to health care is
      constrained by the population's ability to pay. Health expenditures impoverish
      households, creating new poor and impoverishing the already poor. CONCLUSIONS:
      The success of reforms depends largely on the extent to which they remove
      financial barriers to access to services. The experience of Burkina Faso also
      reveals the need for fundamental changes that will motivate staff, improve
      productivity, and ensure good quality services. Integrating health development
      policies with strategic plans for poverty reduction can provide new opportunities
      for African countries to redesign their health systems within this type of
      perspective.

PMID- 17176355
TI  - In vivo sensitivity monitoring of mefloquine monotherapy and artesunate
      mefloquine combinations for the treatment of uncomplicated falciparum malaria in
      Thailand in 2003.

PMID- 17176357
TI  - Using the Delphi technique in economic evaluation: time to revisit the oracle?
AB  - BACKGROUND AND OBJECTIVE: Although the Delphi technique has been commonly used as
      a data source in medical and health services research, its application in
      economic evaluation of medicines has been more limited. The aim of this study was
      to describe the methodology of the Delphi technique, to present a case for using
      the technique in economic evaluation, and to provide recommendations to improve
      such use. METHODS: The literature was accessed through MEDLINE focusing on
      studies discussing the methodology of the Delphi technique and economic
      evaluations of medicines using the Delphi technique. RESULTS AND DISCUSSION: The
      Delphi technique can be used to provide estimates of health care resources
      required and to modify such estimates when making inter-country comparisons. The
      Delphi technique can also contribute to mapping the treatment process under
      investigation, to identifying the appropriate comparator to be used, and to
      ensuring that the economic evaluation estimates cost-effectiveness rather than
      cost-efficacy. CONCLUSION: Ideally, economic evaluations of medicines should be
      based on real-patient data. In the absence of such data, evaluations need to
      incorporate the best evidence available by employing approaches such as the
      Delphi technique. Evaluations based on this approach should state the
      limitations, and explore the impact of the associated uncertainty in the results.

PMID- 17176358
TI  - Treatment of psychosis: 30 years of progress.
AB  - BACKGROUND: Thirty years ago, psychiatrists had only a few choices of old
      neuroleptics available to them, currently defined as conventional or typical
      antipsychotics, as a result schizophrenics had to suffer the severe extra
      pyramidal side effects. Nowadays, new treatments are more ambitious, aiming not
      only to improve psychotic symptoms, but also quality of life and social
      reinsertion. Our objective is to briefly but critically review the advances in
      the treatment of schizophrenia with antipsychotics in the past 30 years. We
      conclude that conventional antipsychotics still have a place when just the cost
      of treatment, a key factor in poor regions, is considered. The atypical
      antipsychotic drugs are a class of agents that have become the most widely used
      to treat a variety of psychoses because of their superiority with regard to extra
      pyramidal symptoms. We can envisage different therapeutic strategies in the
      future, each uniquely targeting a different dimension of schizophrenia, be it
      positive, negative, cognitive or affective symptoms.

PMID- 17176360
TI  - Systematic review of the use of patients' own medications in acute care
      institutions.
AB  - BACKGROUND: Patients' own medications (POM) are medications that patients have
      obtained in the community setting and bring to the hospital when admitted. The
      practice of using POMs has not been well studied. OBJECTIVE: To identify
      benefits, risks and other impacts on the use of POM in hospitals. METHODS: A
      systematic search of the literature and internet was conducted for articles in
      the English language dated from 1984 to 2004. PubMed, CINAHL, IPA, and Embase
      databases were searched with combinations of the following text words: patient,
      own, drug, medication, medicine. References of relevant articles and specific
      journals were hand-searched. RESULTS: Nineteen primary studies that provided
      information on the benefits and risks of POMs were identified. Benefits included
      decreased wastage of POMs, improving the accuracy of admission orders,
      opportunities for patient counselling and continuity of care between acute and
      primary care. Hospitals must address liability and workload concerns but may
      benefit from savings to their drug budget. DISCUSSION: Only a limited number of
      studies were found that addressed the benefits, risks and costs of using POMs in
      hospitals. These studies had small sample sizes with limitations in the quality
      of the study design. Nevertheless, the literature contained examples of benefits
      to the patient and hospital, as well as assistance with practical issues. Further
      research is needed to evaluate the benefits and risks of using POMs. Hospital
      policies should describe identification, storage and documentation procedures to
      address liability and risk concerns. Implementation of policies to use POMs
      should include an evaluation component, which could include a comprehensive
      economic analysis of drug costs and staff workload.

PMID- 17176359
TI  - Carvedilol accelerate elevation of serum potassium in chronic heart failure
      patients administered spironolactone plus furosemide and either enalapril maleate
      or candesartan cilexetil.
AB  - OBJECTIVE: To retrospectively investigate the effect of carvedilol and
      spironolactone plus furosemide, administered concomitantly with an angiotensin II
      converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB)
      to patients with chronic heart failure (CHF). METHODS: Patients with CHF, who
      visited Departments of Cardiovascular Internal Medicine at the National Hospital
      Organization Osaka Medical Center, were enrolled for this study. Serum potassium,
      blood urea nitrogen (BUN), serum creatinine (Scr) and serum sodium were measured
      in every patient at the time of start of treatment and after 3 and 12 months of
      treatment. Data from patients in groups A (20 mg/day carvedilol + 25 mg/day
      spironolactone + 40 mg/day furosemide + an ACE-I) and B (20 mg/day carvedilol +
      25 mg/day spironolactone + 40 mg/day furosemide + ARB) were compared. RESULTS:
      When 20 mg/day carvedilol plus 25 mg/day spironolactone plus 5 mg/day enalapril
      maleate (enalapril, group A) or 8 mg/day candesartan cilexetil (candesartan,
      group B) plus 40 mg/day furosemide were used concomitantly, the mean serum
      potassium increased significantly in both groups of patients. Seven of 59 (11.9%)
      patients had hyperkalemia (>5.5 mEq/L) during 12 months of treatment whereas 8.5%
      of patients (five of 59) had hypokalemia (< or =3.5 mEq/L). CONCLUSION: When
      carvedilol is used concomitantly with spironolactone, furosemide and enalapril or
      candesartan, it is necessary to monitor serum potassium concentration, even if
      spironolactone is administered at a low dose of 25 mg/day.

PMID- 17176361
TI  - Do selective COX-2 inhibitors increase the risk of cerebrovascular events? A meta
      analysis of randomized controlled trials.
AB  - OBJECTIVES: To evaluate the risk of cerebrovascular events (CVEs) associated with
      selective cyclooxygenase-2 inhibitors (coxibs). METHOD: Systematic review and
      meta-analysis of randomized controlled trials (RCTs). A fixed-effect model was
      used to estimate the odds ratios (ORs) for risk of CVE associated with coxibs
      compared against placebo, non-selective non-steroidal anti-inflammatory drugs
      (NSAIDs) and other coxibs. RESULTS: Forty trials (88 116 patients) were included
      in the meta-analysis. The overall pooled OR for CVE for any coxib against placebo
      was 1.03 (95% CI: 0.71, 1.50). Comparing individual coxibs against placebo, we
      found that celecoxib, rofecoxib, etoricoxib and lumiracoxib were associated with
      higher CVE risks and valdecoxib was associated with a lower CVE risk, although
      there were no significant differences detected. There was also no significant
      difference in risk of CVE when comparing coxibs against any non-selective NSAIDs;
      the corresponding pooled OR was 0.86 (95% CI: 0.64, 1.16). CONCLUSION: On the
      basis of a detailed analysis of available RCTs, there does not appear to be any
      significant difference in risk of CVEs associated with coxibs when compared
      against placebo or non-selective NSAIDs. It is likely that the increased risk of
      thrombotic vascular events associated with coxibs is largely attributable to an
      increased risk of myocardial infarction, rather than CVEs.

PMID- 17176362
TI  - Attitudes of Slovene general practitioners towards generic drug prescribing and
      comparison with international studies.
AB  - BACKGROUND: Over the recent years there has been a steady 7% yearly increase in
      prescribing costs, which accounts for 17% of the Slovene national health care
      budget. Substitution of branded products by generic equivalents can offer
      savings. General practitioners (GPs) are often concerned about the quality of
      generic products and possible legal liabilities associated with their use.
      OBJECTIVE: We wanted to examine the attitudes of GPs in Slovenia towards generic
      drug prescribing. METHODS: We conducted a postal survey of a random sample of 200
      out of 800 GPs in Slovenia from the National Health Insurance Institute database.
      GPs were asked 21 questions regarding their knowledge on generic drugs, awareness
      of prescribing costs, prices of generic drugs relative to brand name drugs and
      their attitude towards use of generic drugs. RESULTS: The 117 (58.5%) replies we
      received represent 15% of the GP population in Slovenia. 66.1% of GPs considered
      rising costs of medicines to be a serious problem for the health care budget.
      Each week, over 50% of GPs experienced demands from patients for specific drugs
      and the majority of GPs usually met their patients' demands or requests from
      hospital consultants for branded products. 38.3% of GPs did not take price into
      consideration when prescribing drugs. The majority of GPs (88.9%) perceived
      generics to have the same effectiveness as branded drugs. One quarter of GPs
      would prescribe more generics if additional clinical trials were presented. 37.3%
      would follow advice of academic detailers and 30.3% expected the generics to be
      even cheaper than they were. Independent detailing was welcomed by 63.8% of GPs
      because of the big influence of the pharmaceutical industry on the prescribing
      habits. 15.5% thought that the industry had a tremendous impact on their
      prescribing patterns. CONCLUSIONS: Slovene GPs are aware of the cost of
      prescribed drugs. They are willing to accept independent academic detailing to
      improve their prescribing and are willing to increase generic drugs under certain
      conditions.

PMID- 17176363
TI  - Role of follow-on drugs and indications on the WHO Essential Drug List.
AB  - INTRODUCTION: The World Health Organization's Essential Drug List (EDL) contains
      first-in-class drugs and subsequent class entrants (follow-on drugs) deemed
      necessary to combat diseases prevalent throughout the world, with a special
      emphasis on developing nations. The EDL also includes originally approved and
      follow-on indications. There are opposing views regarding the value of follow-on
      drugs and indications. Critics suggest many follow-on drugs and indications offer
      little or no benefit to patients. Advocates counter that follow-on drugs offer
      advantages in terms of improved effectiveness, compliance and patient
      satisfaction. OBJECTIVE: In order to inform this debate on the value of follow-on
      drugs and indications we examined the numbers of follow-on drugs on the EDL and
      the extent to which follow-on indications are recommended. METHODS: We identified
      all 312 drugs on the 14th edition of the EDL, omitting 72 non-pharmaceutical
      entities. For the 240 pharmaceutical entities we ascertained whether the Food and
      Drug Administration (FDA) had approved them, and, if so, when each was approved.
      We chose a validated therapeutic classification system - the United States
      Pharmacopeia's Model Guidelines for Medicare formulary management - in order to
      distinguish first-in-class and follow-on drugs on the EDL. Specifically, we
      selected the formulary key drug type as our benchmark therapeutic class. We
      assigned each EDL drug to a formulary key drug type. We defined first-in-class
      drugs as the first in each formulary key drug type, and follow-on drugs as all
      other drugs in each formulary key drug type. We identified follow-on indications
      by comparing WHO-listed indications with the original approved indication(s) by
      the FDA. Finally, we examined the therapeutic rating (priority vs. standard)
      given by the FDA to follow-on drugs on the EDL. RESULTS: Sixty-three per cent of
      the EDL drugs were follow-ons; 15% of the indications were follow-on indications.
      Fourteen drugs were listed in multiple WHO (sub) groupings; and 49% of follow-on
      drugs were given a priority rating by the FDA. CONCLUSIONS: In light of the fact
      that the EDL only includes drugs and indications deemed essential, the large
      number of follow-on drugs, follow-on indications, and priority-rated follow-on
      drugs on the EDL suggest their importance. From a public policy perspective, it
      may prove counterproductive to erect hurdles that impede follow-on research and
      development.

PMID- 17176364
TI  - Long-term effects of antidepressants on cognition in patients with Alzheimer's
      disease.
AB  - PURPOSE: Approximately 25-40% of patients with Alzheimer's disease (AD) may
      develop depression. Antidepressants are typically used to treat depression in
      this population. However, their effect on cognition has been rarely studied and
      the results are conflicting. In addition, the long-term effects of
      antidepressants on cognition have not been studied. Therefore, the objective of
      the study was to evaluate the effects on cognition in patients with AD treated
      with antidepressants for at least 9 months. METHODS: Data on antidepressant use
      over a minimum period of 9 months were retrospectively collected for patients
      with AD receiving cholinesterase inhibitors. Data on cognition were analyzed to
      compare those taking antidepressant therapy and those not receiving
      antidepressants. RESULTS: Ninety-nine of 210 patients met our inclusion criteria.
      Fifty-eight patients were prescribed an antidepressant (e.g. selective serotonin
      reuptake inhibitors (SSRIs), newer generation antidepressants). Sertraline (mean
      dose: 82 mg/day) and citalopram (mean dose: 35 mg/day) were the most commonly
      prescribed antidepressants. The baseline mean Mini Mental State Examination
      (MMSE) score was 16.32 with an average annual rate of cognitive decline of 2.55
      for patients receiving antidepressants compared with 16.59 (P = NS) and 2.27 (P =
      NS) for those not taking antidepressants. CONCLUSIONS: Our small sample data
      indicate no differences in baseline MMSE scores and cognitive decline between the
      two groups, suggesting antidepressants did not contribute significantly to
      cognitive decline over a utilization period of at least 9 months.

PMID- 17176365
TI  - Echinacea purpurea supplementation stimulates select groups of human
      gastrointestinal tract microbiota.
AB  - BACKGROUND AND OBJECTIVE: The objective of this research was to determine the
      effects of the dietary supplement Echinacea purpurea on aerobic and anaerobic
      bacteria common to the human gastrointestinal (GI) tract. Botanical extracts have
      shown in vitro antimicrobial effects against certain pathogenic bacteria. It is
      uncertain if medicinal herbs have any effect against pathogenic bacteria or on
      the native GI microbiota. METHODS: Fifteen human subjects consumed 1000 mg of
      standardized E. purpurea for 10 days. Faecal samples were collected at baseline,
      10 days and 17-18 days following supplementation. Samples were tested for select
      aerobic and anaerobic bacteria using plate culture microbiological methods.
      RESULTS AND DISCUSSION: Significant increases were found for total aerobic
      bacteria, Bacteroides group and Bacteroides fragilis after E. purpurea exposure.
      Supplementation did not significantly alter the number of enteric bacteria,
      enterococci, lactobacilli, bifidobacteria or total anaerobic bacteria.
      CONCLUSION: Echinacea supplementation has altered the GI microbiota. The health
      consequences associated with this change are unknown but previous research has
      shown increased Bacteroides concentrations associated with diarrhoea,
      inflammatory bowel disease and increased risk of colon cancer. Additional
      research should delineate the role of Echinacea in the stimulation of Bacteroides
      and describe the effects of other botanical supplements to the GI microbiota.

PMID- 17176366
TI  - Adherence to treatment in Swedish HIV-infected patients.
AB  - OBJECTIVES: The objectives were to assess the prevalence of adherence to
      antiretroviral treatment in Swedish human immunodeficiency virus (HIV)-infected
      patients and to evaluate factors associated with adherence. METHODS: All HIV
      treated patients, who attended one of 30 (of a total of 32) Swedish infectious
      diseases clinics, during 7 months, were asked to complete an anonymous
      questionnaire containing the 9-item Morisky Medication Adherence Scale (MMAS) and
      questions about other factors potentially affecting adherence. The summary score
      of MMAS ranges from 1 to 13, where 13 indicates perfect adherence; patients
      scoring 11 or above (corresponding to 95% adherence level) were classified as
      'adherent'. RESULTS AND DISCUSSION: In total 946 patients participated (response
      rate 97.5%). The proportion of patients who reported not missing a dose during
      the day prior to the completion of the questionnaire was 97% and the proportion
      classified as 'adherent' was 63%. 'Adherent' patients were more likely to have a
      good relationship with their health care professionals (P < 0.05) and not have
      problems with drugs or alcohol (P < 0.01). Being older (P < 0.01) and having a
      shorter time on current treatment (P < 0.01) and on treatment in total (P < 0.05)
      were factors also associated with good adherence. CONCLUSION: Factors modifiable
      for interventions by health care professionals are patient-provider relationship,
      drug or alcohol problems and patients with long treatment periods.

PMID- 17176367
TI  - Inappropriate prescribing in the elderly: a comparison of the Beers criteria and
      the improved prescribing in the elderly tool (IPET) in acutely ill elderly
      hospitalized patients.
AB  - BACKGROUND: In appropriate prescribing is a significant and persistent problem in
      elderly people, both in hospital and the community and has been described in
      several countries in Europe and also the USA. The problem of inappropriate
      prescribing has not been quantified in the Republic of Ireland. The most commonly
      used criteria for the identification of inappropriate prescribing are the Beers'
      criteria [both independent of diagnosis (ID) and considering diagnosis (CD) -
      2003 version]. The Beers' criteria ID includes 48 different categories of either
      single medications or multiple medications of a similar class identified as
      inappropriate prescriptions and the Beers' criteria CD contains 19 different
      categories containing possible drug-disease interactions. A second tool, the
      improved prescribing in the elderly tool (IPET) has also been validated and used
      in hospital and community studies and has 14 categories of either explicitly
      contraindicated medications or possible drug-disease interactions. OBJECTIVES:
      The primary aim of the study is to measure the incidence of inappropriate
      prescribing among older community-dwelling individuals presenting to an acute
      hospital in the Republic of Ireland. A secondary aim of this study was also
      therefore to compare the efficacy of the above two tools in identifying
      inappropriate prescribing. METHODS: A prospective, consecutive observational
      cohort study was carried out over a 4-month period. The setting was an urban
      based university hospital acute geriatric medicine assessment unit. Subjects in
      this study (n = 350) were consecutively screened on admission to hospital (mean
      age = 80.3 +/- 6.1 years) and all patients had both Beers' criteria ID and CD and
      IPET applied to their list of prescription drugs on admission, cross-referenced
      with their list of current active medical diagnosis. RESULTS: The results of the
      study identified a high rate of inappropriate prescribing among this population
      of community-dwelling subjects. The total number of inappropriate prescriptions
      identified using the Beers' criteria (ID) was 148 affecting 121 patients. The
      Beers' criteria (CD) identified 69 inappropriate prescriptions in 60 patients and
      the IPET identified 112 inappropriate prescriptions in 78 patients. The Beers
      criteria (ID and CD combined) identified at least one inappropriate prescription
      in 34% of subjects and the IPET identified one in at least 22% of subjects.
      CONCLUSIONS: This study identifies high rates of use of inappropriate medications
      in community-dwelling elderly presenting with acute illness to hospital. These
      are comparable with inappropriate prescribing rates identified in previous
      studies. The revised Beers' criteria (2003) identified more inappropriate
      prescriptions than the IPET in this population of elders.

PMID- 17176369
TI  - An improved rapid genotyping method for the study of beta-2 adrenergic receptor
      gene polymorphisms using single tube allele specific multiplex PCR.
AB  - BACKGROUND: Seventeen single nucleotide polymorphisms (SNPs) have been identified
      so far, within the beta-2 receptor (beta(2) AR) gene. The presence of so many
      SNPs within the beta(2) AR gene causes a problem, for those studying beta(2) AR
      pharmacogenetics, in relation to which SNPs to choose. Most of the work has
      focused on the three common SNPs within the coding block (alleles 16, 27 and 164)
      and the techniques developed have been for these three functionally important
      alleles. OBJECTIVE: We report an improved polymerase chain reaction (PCR)-based
      method for the simultaneous detection of five functionally important beta(2) AR
      alleles, namely beta 16A/G, beta utr-20C/T, beta 27C/G, beta utr-47C/T and beta
      164C/T. METHODS: Genomic DNA was used as a template for duplex and triplex PCR to
      detect the polymorphic sites of the five alleles. RESULT: DNA sequencing analysis
      confirmed the specificity of this PCR method. CONCLUSION: This simplified single
      tube multiplexed PCR assay provides an easier, faster and more cost-effective
      method than those available for studying the specified polymorphisms of the
      beta(2)AR gene.

PMID- 17176368
TI  - TPMT genotype and its clinical implication in renal transplant recipients with
      azathioprine treatment.
AB  - BACKGROUND: Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of
      thiopurine drugs. Patients with intermediate or deficient TPMT activity are at
      risk of toxicity after receiving standard doses of these drugs. OBJECTIVE: This
      study determined the frequencies of TPMT alleles (TPMT*2, *3A, *3B and *3C) and
      explored the association between TPMT genetic polymorphism and the development of
      adverse drug reactions in Chinese renal transplant patients receiving
      azathioprine (AZA). METHODS: TPMT genotypes were determined using polymerase
      chain reaction-based assays in 122 renal transplant patients and 210 healthy
      subjects. Biochemical and clinical data were retrospectively evaluated after
      renal transplantation. RESULTS: Of 122 patients, eight (allele frequency 3.28%)
      were heterozygous for TPMT*3C and no TPMT*2, *3A or *3B or homozygous TPMT*3C
      subjects were identified. The pattern and frequency of the main mutant TPMT
      alleles were similar in patients and healthy subjects. Four of five patients
      (80%) with haematopoietic toxicity were heterozygotes. TPMT heterozygosity was
      associated with significant reductions in haematological indices and a
      significant decrease in cyclosporine plasma concentrations in the first year
      after renal transplantation. No association between TPMT genotype and renal
      rejection was identified. CONCLUSION: Our results, together with those of others
      pointing in the same direction, suggest that genotyping the major TPMT variant
      alleles may be a valuable tool in preventing AZA toxicity and optimization of
      immunosuppressive therapy.

PMID- 17176370
TI  - Stability of moxifloxacin injection in peritoneal dialysis solution bags (Dianeal
      PD1 1.36% and Dianeal PD1 3.86%).
AB  - BACKGROUND AND OBJECTIVE: Moxifloxacin is a new fluorquinolone with broad
      spectrum activity. It is suitable for treating peritonitis in peritoneal dialysis
      (PD) patients. The objective of this study was to test stability of moxifloxacin
      in PD solutions stored at different temperatures. METHODS: Dialysis solution bags
      were used at two glucose concentrations; Dianeal PD1 1.36% and Dianeal PD1 3.86%.
      Moxifloxacin solution (2%) was injected into nine 2-L bags of Dianeal PD1 1.36%
      and nine bags of Dianeal PD1 3.86% under aseptic conditions to achieve a nominal
      concentration of 25 mg/L. Three bags of Dianeal PD1 1.36% and three bags of
      Dianeal PD1 3.86% were stored at each of three temperatures (4, 25 and 37 degrees
      C) and the same way for. Duplicate samples (2 mL) were taken at different times
      and precipitation, cloudiness, colour and pH was analysed. Moxifloxacin
      concentrations were measured using a modified HPLC method. RESULTS: The mean
      moxifloxacin concentration in the Dianeal PD1 1.36% solution remained > or =90%
      of the initial concentration for 14 days at 4 degrees C, 7 days at 25 degrees C
      and 3 days at 37 degrees C. For Dianeal PD1 3.86% moxifloxacin concentrations
      remained > or =90% for 14 days at 4 degrees C, 3 days at 25 degrees C and 12 h at
      37 degrees C. CONCLUSIONS: Moxifloxacin shows sufficient stability in both PD
      bags for use in PD patients.

PMID- 17176371
TI  - Adverse effect of TNF-alpha blocker? Demyelination in an ankylosing spondylitis
      patient: a case report.
AB  - Anti-tumour necrosis factor (TNF)-alpha agents promise better disease control for
      treatment of inflammatory arthritides which are resistant to classical disease
      modifying treatment and provide better functional outcome. But these agents are
      not free of adverse events. The exact relationship between use of anti-TNF drugs
      and development of demyelination cannot be established yet. Here we present a
      case of a 36-year-old man who developed demyelination in the cervical spinal cord
      while he was being treated with etanercept for ankylosing spondylitis.

PMID- 17176372
TI  - Are we aware of hospital patients' drug allergies?

PMID- 17176375
TI  - Practitioner review: assessment and treatment of refugee children and adolescents
      who have experienced war-related trauma.
AB  - BACKGROUND: Increasingly clinicians are being asked to assess and treat young
      refugees, who have experienced traumatic events due to war and organised
      violence. However, evidence-based guidance remains scarce. METHOD: Published
      studies on the mental health difficulties of refugee children and adolescents,
      associated risk and protective factors, as well as effective interventions,
      particularly those designed to reduce war-related post-traumatic stress disorder
      (PTSD) symptoms, were identified and reviewed. The findings are summarised.
      RESULTS: Young refugees are frequently subjected to multiple traumatic events and
      severe losses, as well as ongoing stressors within the host country. Although
      young refugees are often resilient, many experience mental health difficulties,
      including PTSD, depression, anxiety and grief. An awareness of relevant risk and
      protective factors is important. A phased model of intervention is often useful
      and the need for a holistic approach crucial. Promising treatments for
      alleviating symptoms of war-related PTSD include cognitive behavioural treatment
      (CBT), testimonial psychotherapy, narrative exposure therapy (NET) and eye
      movement desensitisation and reprocessing (EMDR). Knowledge of the particular
      needs of unaccompanied asylum-seeking children (UASC), working with interpreters,
      cross-cultural differences, medico-legal report writing and the importance of
      clinician self-care is also necessary. CONCLUSION: More research is required in
      order to expand our limited knowledge base.

PMID- 17176376
TI  - The impact of structured activities among Palestinian children in a time of
      conflict.
AB  - BACKGROUND: There is growing evidence of the impact on children's well-being of
      exposure to political conflict in such settings as the Palestinian territories.
      This study examined the impact of child-focused interventions involving
      structured activities, supported by provision of equipment and training of
      facilitators. The focus of interventions was participation in recreational,
      cultural and other non-formal activities supporting the development of
      resilience. Impacts were hypothesised on children's social and emotional well
      being, relationships with parents and degree of future orientation. METHODS: Two
      hundred and fifty children from the West Bank and 150 children from Gaza took
      part in the study. Of these 400 children, 300 comprised the intervention group.
      Fifty children from Gaza and 50 children from the West Bank comprised the
      comparison group. There were equal numbers of girls and boys in all groups, with
      similar proportions of children aged between 6 and 11 years, and between 12 and
      17 years. Measures used were the Child Behavior Checklist (CBCL), the Parental
      Support Scale and the Hopefulness Scale: Youth Version. Assessment was made as
      children enrolled on the structured activity programmes (T1) and again twelve
      months later (T2). RESULTS: There was no difference in the CBCL Total,
      Internalising or Externalising problem scores at baseline (Time 1) between the
      children who subsequently took the intervention and those who did not. Compared
      to children in the comparison group, children in the intervention group had lower
      CBCL total problem scores, externalising problem scores, and internalising
      problem scores at Time 2 compared to Time 1. Exposure to the intervention was not
      associated with changes in children's hopefulness, but those receiving the
      intervention in the West Bank did report improved parental support at Time 2.
      CONCLUSIONS: The intervention appeared successful in improving children's
      emotional and behavioural well-being but not hopefulness. It was also linked with
      increased parental support in some areas (those located in the West Bank).

PMID- 17176378
TI  - The Emanuel Miller Memorial Lecture 2006: adoption as intervention. Meta-analytic
      evidence for massive catch-up and plasticity in physical, socio-emotional, and
      cognitive development.
AB  - BACKGROUND: Adopted children have been said to be difficult children, scarred by
      their past experiences in maltreating families or neglecting orphanages, or by
      genetic or pre- and perinatal problems. Is (domestic or international) adoption
      an effective intervention in the developmental domains of physical growth,
      attachment security, cognitive development and school achievement, self-esteem,
      and behaviour problems? METHOD: Through a series of meta-analyses on more than
      270 studies that include more than 230,000 adopted and non-adopted children and
      their parents an adoption catch-up model was tested. RESULTS: Although catch-up
      with current peers was incomplete in some developmental domains (in particular,
      physical growth and attachment), adopted children largely outperformed their
      peers left behind. Adoptions before 12 months of age were associated with more
      complete catch-up than later adoptions for height, attachment, and school
      achievement. International adoptions did not lead to lower rates of catch-up than
      domestic adoptions in most developmental domains. CONCLUSIONS: It is concluded
      that adoption is an effective intervention leading to massive catch-up. Domestic
      and international adoptions can be justified on ethical grounds if no other
      solutions are available. Humans are adapted to adopt, and adoption demonstrates
      the plasticity of child development.

PMID- 17176377
TI  - Pre-attack stress-load, appraisals, and coping in children's responses to the
      9/11 terrorist attacks.
AB  - BACKGROUND: Appraisal and coping following a disaster are important factors in
      children's post-traumatic stress (PTS) symptoms. However, little is known about
      predictors of disaster coping responses. This study examined stress-load,
      appraisals and coping styles measured prior to the September 11 terrorist attacks
      as predictors of 9/11-specific appraisals, coping and PTS. METHODS: A community
      sample of children and parents (N = 143) participating in an ongoing study were
      interviewed by phone approximately 1 month following 9/11. RESULTS: Pre-attack
      stress-load, appraisal and coping styles predicted children's 9/11-specific
      appraisals, coping, and PTS. 9/11-specific threat appraisals and avoidant coping
      predicted higher PTS and mediated the effects of pre-attack stress-load and
      threat appraisal. CONCLUSIONS: Pre-disaster stress-load, appraisal and coping
      styles predict disaster-specific appraisal and coping, which in turn, contribute
      to PTS. Coping interventions might mitigate PTS symptoms following a disaster.

PMID- 17176379
TI  - The development of adopted children after institutional care: a follow-up study.
AB  - BACKGROUND: Research suggests that institutional care has long-lasting effects on
      children. However, no study has longitudinally studied infants in an institution
      and their subsequent development at age four. METHODS: Sixty-one adopted children
      aged four years who had spent their first two years of life in an institution
      were compared to 39 children reared in their own two-parent families. Cognitive
      development, security of attachment, shyness, children's emotional understanding
      and behavioural problems were examined in both groups. Parental health and stress
      were also assessed. RESULTS: At four years adopted children still had lower
      scores on cognitive development, were less secure, and less able to understand
      emotions than family-reared children. Children with a secure attachment type in
      infancy were found to be less secure at age four, compared with those who were
      classified in infancy as having an insecure attachment type. Their physical
      development had recovered, they were less shy, had no behavioural problems and no
      problems in the relationship with their teacher. CONCLUSIONS: Early residential
      group care has long-lasting effects on important socio-emotional and cognitive
      aspects of preschool children's development.

PMID- 17176380
TI  - Efficacy of Interpersonal Psychotherapy-Adolescent Skills Training: an indicated
      preventive intervention for depression.
AB  - BACKGROUND: Indicated interventions for adolescents with elevated depressive
      symptoms may help decrease rates of depression. The current study reports on the
      efficacy of Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST), a
      group indicated preventive intervention. METHODS: Forty-one adolescents with
      elevated depression symptoms were randomized to receive either IPT-AST or school
      counseling (SC) as delivered by guidance counselors and social workers.
      Adolescents in the two intervention conditions were compared on depression
      symptoms, overall functioning, and depression diagnoses post-intervention and at
      3-month and 6-month follow-up. RESULTS: Adolescents who received IPT-AST had
      significantly fewer depression symptoms and better overall functioning post
      intervention and at follow-up. Adolescents in IPT-AST also reported fewer
      depression diagnoses than adolescents in usual care. CONCLUSIONS: These results
      provide preliminary evidence of the efficacy of IPT-AST as an intervention for
      adolescents with subthreshold depression. Future research is needed to confirm
      the efficacy of IPT-AST in a larger and more diverse sample and to determine its
      long-term impact on depression symptoms and depression diagnoses.

PMID- 17176381
TI  - Is there an epidemic of child or adolescent depression?
AB  - BACKGROUND: Both the professional and the general media have recently published
      concerns about an 'epidemic' of child and adolescent depression. Reasons for this
      concern include (1) increases in antidepressant prescriptions, (2) retrospective
      recall by successive birth cohorts of adults, (3) rising adolescent suicide rates
      until 1990, and (4) evidence of an increase in emotional problems across three
      cohorts of British adolescents. METHODS: Epidemiologic studies of children born
      between 1965 and 1996 were reviewed and a meta-analysis conducted of all studies
      that used structured diagnostic interviews to make formal diagnoses of depression
      on representative population samples of participants up to age 18. The effect of
      year of birth on prevalence was estimated, controlling for age, sex, sample size,
      taxonomy (e.g., DSM vs. ICD), measurement instrument, and time-frame of the
      interview (current, 3 months, 6 months, 12 months). RESULTS: Twenty-six studies
      were identified, generating close to 60,000 observations on children born between
      1965 and 1996 who had received at least one structured psychiatric interview
      capable of making a formal diagnosis of depression. Rates of depression showed no
      effect of year of birth. There was little effect of taxonomy, measurement
      instrument, or time-frame of interview. The overall prevalence estimates were:
      under 13, 2.8% (standard error (SE) .5%); 13-18 5.6% (SE .3%); 13-18 girls: 5.9%
      (SE .3%); 13-18 boys: 4.6% (SE .3%). CONCLUSIONS: When concurrent assessment
      rather than retrospective recall is used, there is no evidence for an increased
      prevalence of child or adolescent depression over the past 30 years. Public
      perception of an 'epidemic' may arise from heightened awareness of a disorder
      that was long under-diagnosed by clinicians.

PMID- 17176382
TI  - Gender-specific development of nonverbal behaviours and mild depression in
      adolescence.
AB  - BACKGROUND: Individual differences in depressive symptoms have been linked with
      social skill deficits in adults and children, yet empirical studies on
      adolescents are lacking. The present research examines age and gender differences
      in nonverbal behaviour between mildly depressed and nondepressed (pre-)
      adolescents during conversations with an adult (study 1) and a same-aged peer
      (study 2). Both studies also examine whether conversation partners respond
      differently to mildly depressed versus nondepressed (pre)adolescents. METHODS:
      Study 1 reports on observations of conversations of 9-15-year-old children (n =
      122) with a female adult partner. Study 2 reports findings of observations of 12
      17-year-old adolescents (n = 154) in conversation with same-age, same-sex peers.
      RESULTS: Both studies show gender and/or age effects in gazing, smiling and
      backchannel behaviours that indicate that as adolescents mature they increasingly
      behave according to gender-specific display rules. While talking to an adult,
      depressed (pre-)adolescents and the adult partner differed in backchannel
      behaviours. While talking to peers, only depressed adolescent girls showed less
      gazing towards the partner during listening. Moreover, adolescents smiled less
      often towards depressed than nondepressed partners. CONCLUSIONS: Gender-specific
      development of nonverbal behaviour may help to understand the development of
      gender differences in depression in adolescence. Females who fail to exhibit
      other-oriented social skills may be particularly at risk for depressive symptoms.

PMID- 17176383
TI  - Attention difficulties and mood-related ruminative response style in adolescents
      with unipolar depression.
AB  - BACKGROUND: Depressed adults may show impairment in switching attention from one
      task to another. Rumination on negative thoughts is associated with the onset and
      persistence of depressive episodes. It is unclear if such mood-related
      ruminations are specifically associated with slowed ability in switching
      attention from one task to another. METHOD: Adolescents with current unipolar
      depression (n = 40) were compared with age and sex-matched controls (n = 38) on
      tests of attention and general cognitive abilities and completed the mood-related
      ruminative response style questionnaire. RESULTS: Compared to controls, depressed
      participants were significantly slower at switching attention. There was no
      association between attentional switching and mood-related ruminations and both
      processes contributed to the likelihood of being depressed. Findings were not
      accounted for by slowness in reading and speaking, the effects of antidepressants
      nor being more careful on tasks. CONCLUSIONS: Depressed adolescents demonstrate
      dual deficits in mood-related ruminative thinking and attention. Further studies
      are needed to investigate whether higher ruminations are associated with
      attention impairments in emotionally-valent attentional switching tasks, and
      whether both processes precede the emergence of clinical disorder.

PMID- 17176384
TI  - Risk factors for preschool depression: the mediating role of early stressful life
      events.
AB  - BACKGROUND: Family history of mood disorders and stressful life events are both
      established risk factors for childhood depression. However, the role of mediators
      in risk trajectories, which are potential targets for intervention, remains
      understudied. To date, there have been no investigations of mediating
      relationships between risk factors and very early onset depression, a
      developmental period during which intervention may be more effective. The current
      study used regression analyses to examine the relationships between family
      history of mood disorders and stressful life events as risk factors for
      depression in a preschool sample. METHOD: Preschoolers 3.0 to 5.6 years of age
      participated in a comprehensive mental health assessment. Caregivers were
      interviewed about their children using a structured diagnostic measure to derive
      DSM-IV major depressive disorder (MDD) diagnoses and dimensional depression
      severity scores. Family history of psychiatric disorders and preschoolers'
      stressful life events was obtained. RESULTS: Both family history and stressful
      life events predicted depression severity scores 6 months later. Analyses
      examining the influence of family history of mood disorders and stressful life
      events on preschoolers' depression severity demonstrated that stressful life
      events mediated the relationship between family history and preschoolers'
      depression. CONCLUSIONS: Findings outline the key role of exposure to early
      stressful life events as a mediator of familial mood disorder risk in preschool
      onset depression. This finding in a preschool sample provides support for the
      hypothesis that psychosocial factors may have increased importance as mediators
      of risk in younger age groups. Findings suggest that psychosocial factors should
      be considered key targets for early intervention in depression.

PMID- 17176385
TI  - The impact of alcohol-specific rules, parental norms about early drinking and
      parental alcohol use on adolescents' drinking behavior.
AB  - BACKGROUND: The present study explores the role of having rules about alcohol,
      parental norms about early alcohol use, and parental alcohol use in the
      development of adolescents' drinking behavior. It is assumed that parental norms
      and alcohol use affect the rules parents have about alcohol, which in turn
      prevents alcohol use by adolescent children. METHODS: Longitudinal data collected
      from 416 families consisting of both parents and two adolescents (aged 13 to 16
      years) were used for the analyses. RESULTS: Results of structural equation
      modeling show that having clear rules decreases the likelihood of drinking in
      adolescence. However, longitudinally alcohol-specific rules have only an indirect
      effect on adolescents' alcohol use, namely through earlier drinking. Analyses
      focusing on explaining the onset of drinking revealed that having strict rules
      was related to the postponement of drinking initiation of older and younger
      adolescents. Further, parental norms about adolescents' early drinking and
      parental alcohol use were associated with having alcohol-specific rules. Parental
      norms were also related to adolescents' alcohol use. CONCLUSIONS: The current
      study is one of the first using a full family design to provide insight into the
      role of alcohol-specific rules on adolescents' drinking. It was shown that having
      strict rules is related to postponement of drinking, and that having alcohol
      specific rules depends on other factors, thus underlining the complexity of the
      influence of parenting on the development of adolescents' alcohol use.

PMID- 17176387
TI  - Highlighting the multiple drivers of change in interactions along stress
      gradients.

PMID- 17176388
TI  - Life history variation in Thlaspi caerulescens.

PMID- 17176389
TI  - Root-sprouting in myco-heterotrophic plants: prepackaged symbioses or overcoming
      meristem limitation?

PMID- 17176390
TI  - Functional biology of plant phosphate uptake at root and mycorrhiza interfaces.
AB  - Phosphorus (P) is an essential plant nutrient and one of the most limiting in
      natural habitats as well as in agricultural production world-wide. The control of
      P acquisition efficiency and its subsequent uptake and translocation in vascular
      plants is complex. The physiological role of key cellular structures in plant P
      uptake and underlying molecular mechanisms are discussed in this review, with
      emphasis on phosphate transport across the cellular membrane at the root and
      arbuscular-mycorrhizal (AM) interfaces. The tools of molecular genetics have
      facilitated novel approaches and provided one of the major driving forces in the
      investigation of the basic transport mechanisms underlying plant P nutrition.
      Genetic engineering holds the potential to modify the system in a targeted way at
      the root-soil or AM symbiotic interface. Such approaches should assist in the
      breeding of crop plants that exhibit improved P acquisition efficiency and thus
      require lower inputs of P fertilizer for optimal growth. Whether engineering of P
      transport systems can contribute to enhanced P uptake will be discussed.

PMID- 17176392
TI  - A transient decrease in reactive oxygen species in roots leads to root hair
      deformation in the legume-rhizobia symbiosis.
AB  - * A possible role for reactive oxygen species (ROS) in root hair deformation in
      response to Nod factor (NF) was investigated using Medicago truncatula nodulation
      mutants, and an inhibitor and precursors of ROS. * In wild-type roots, ROS efflux
      transiently decreased approximately 1 h after NF treatment. Transcript
      accumulation of two NADPH oxidase homologs, respiratory burst oxidase homolog 2
      (MtRBOH2) and MtRBOH3, also transiently decreased at 1 h. However, in the
      nonnodulating mutant Nod factor perception (nfp), transcript accumulation did not
      change. * Exogenous application of ROS prevented root hair swelling and branching
      induced by NF. When accumulation of ROS was prevented by diphenylene iodonium
      (DPI), NF did not induce root hair branching. Root treatment with DPI alone
      reduced ROS efflux and induced root hair tip swelling. Transient treatment of
      roots with DPI mimicked NF treatment and resulted in root hair branching in the
      absence of NF. A transient DPI treatment did not induce root hair branching in
      the nonlegumes Arabidopsis thaliana and tomato (Lycopersicon esculentum). * The
      results suggest a role for the transient reduction of ROS accumulation in
      governing NF-induced root hair deformation in legumes.

PMID- 17176391
TI  - Calcium-calmodulin is required for abscisic acid-induced antioxidant defense and
      functions both upstream and downstream of H2O2 production in leaves of maize (Zea
      mays) plants.
AB  - * Using pharmacological and biochemical approaches, the role of calmodulin (CaM)
      and the relationship between CaM and hydrogen peroxide (H(2)O(2)) in abscisic
      acid (ABA)-induced antioxidant defense in leaves of maize (Zea mays) plants were
      investigated. * Treatment with ABA or H(2)O(2) led to significant increases in
      the concentration of cytosolic Ca(2+) in the protoplasts of mesophyll cells and
      in the expression of the calmodulin 1 (CaM1) gene and the content of CaM in
      leaves of maize plants, and enhanced the expression of the antioxidant genes
      superoxide dismutase 4 (SOD4), cytosolic ascorbate peroxidase (cAPX), and
      glutathione reductase 1 (GR1) and the activities of the chloroplastic and
      cytosolic antioxidant enzymes. The up-regulation of the antioxidant enzymes was
      almost completely blocked by pretreatments with two CaM antagonists. *
      Pretreatments with CaM antagonists almost completely inhibited ABA-induced
      H(2)O(2) production throughout ABA treatment, but pretreatment with an inhibitor
      or scavenger of reactive oxygen species (ROS) did not affect the initial increase
      in the contents of CaM induced by ABA. * Our results suggest that Ca(2+)-CaM is
      involved in ABA-induced antioxidant defense, and that cross-talk between Ca(2+)
      CaM and H(2)O(2) plays a pivotal role in ABA signaling.

PMID- 17176393
TI  - The rice genome encodes two vacuolar invertases with fructan exohydrolase
      activity but lacks the related fructan biosynthesis genes of the Pooideae.
AB  - * Fructans are believed to contribute to cold and drought tolerance in several
      plant families (Poaceae, Asparagaceae and Asteraceae), but it is not clear why
      the ability to accumulate these polymers is found in some genera (e.g. Triticum)
      but not in others (e.g. Oryza). * As fructan biosynthesis enzymes (FBEs) evolved
      from vacuolar invertases (VINs), we searched the rice genome sequence for genes
      related to both FBE and VIN genes of wheat and other members of the Pooideae. We
      compared them at the levels of exon-intron structure, protein sequence, and the
      enzymatic properties of recombinant proteins after expression in the yeast Pichia
      pastoris. * We found that rice possesses two VIN genes (OsVIN1 and OsVIN2) and no
      FBE genes. FBE genes appear to have arisen in the Pooideae by a series of gene
      duplications from an ancestor of wheat TaVIN3. Recombinant TaVIN2, OsVIN1 and
      OsVIN2 behaved as invertases with no FBE activity, but possessed high fructan
      exohydrolase activity, especially OsVIN1. * The engineering of fructan
      accumulation into rice for greater stress tolerance could founder on endogenous
      exohydrolases, but the fact that OsVIN1 transcripts are absent from peduncles of
      well watered and drought-stressed plants removes one potential obstacle to this
      endeavour.

PMID- 17176394
TI  - Structural motifs of syringyl peroxidases predate not only the gymnosperm
      angiosperm divergence but also the radiation of tracheophytes.
AB  - * The most distinctive variation in the monomer composition of lignins in
      vascular land plants is that found between the two main groups of seed plants.
      Thus, while gymnosperm lignins are typically composed of guaiacyl (G) units,
      angiosperm lignins are largely composed of similar levels of G and syringyl (S)
      units. * However, and contrary to what might be expected, peroxidases isolated
      from basal (Cycadales and Ginkgoales) and differentially evolved (Coniferales and
      Gnetales) gymnosperms are also able to oxidize S moieties, and this ability is
      independent of the presence or absence of S-type units in their lignins. * The
      results obtained led us to look at the protein database to search for homologies
      between gymnosperm peroxidases and true eudicot S-peroxidases, such as the Zinnia
      elegans peroxidase. * The findings showed that certain structural motifs
      characteristic of eudicot S-peroxidases (certain amino acid sequences and beta
      sheet secondary structures) predate the gymnosperm-angiosperm divergence and the
      radiation of tracheophytes, since they are found not only in peroxidases from
      basal gymnosperms, ferns and lycopods, but also in peroxidases from the moss
      Physcomitrella patens (Bryopsida) and the liverwort Marchantia polymorpha
      (Marchantiopsida), which, as typical of bryophytes, do not have xylem tissue nor
      lignins.

PMID- 17176395
TI  - Floral meristem indeterminacy depends on flower position and is facilitated by
      acarpellate gynoecium development in Impatiens balsamina.
AB  - * Floral meristems are generally determinate. Termination of their activity
      varies with species, occurring after carpel or ovule development, depending on
      the placentation type. In terminal flowering Impatiens balsamina (cv. Dwarf Bush
      Flowered) some flowers exhibit meristem indeterminacy; they produce organs from
      the placenta after ovule development. * Here we provide a detailed description of
      gynoecium development in this line and explore the basis of the indeterminate
      nature of some of its floral meristems. * We find that the placenta is sometimes
      established without complete carpel fusion. Proliferative growth derives from
      meristematic remnants of the placenta and is more common in the terminal
      inflorescence. RNA in situ hybridization reveals that IbLFY (Impatiens LFY
      homologue) is expressed in all meristem states, even in proliferating meristems.
      Expression of IbAG in axillary flowers is as expected in the meristem, stamens
      and carpels but absent from the proliferating meristem. * We conclude that I.
      balsamina has cauline placentation. Incomplete suppression of inflorescence
      identity in flowers of the terminal inflorescence leads to floral meristem
      proliferation after ovule development in this species.

PMID- 17176396
TI  - Functional ecology of a blue light photoreceptor: effects of phototropin-1 on
      root growth enhance drought tolerance in Arabidopsis thaliana.
AB  - * The blue light photoreceptor phototropin-1 has been shown to enhance fitness in
      Arabidosis thaliana under field conditions. Here, we ask whether performance
      consequences of phototropin-1 reflect its impact on root growth and drought
      tolerance. * We used a PHOT1-GFP gene construct to test whether phototropin-1
      abundance in roots is highest at shallow soil depths where light penetration is
      greatest. We then compared root growth efficiency and size at maturity between
      individuals with and without functional phototropin-1. Comparisons were made
      under wet and dry conditions to assess the impact of phototropin-1 on drought
      tolerance. * Phototropin-1 was most abundant in upper root regions and its impact
      on root growth efficiency decreased with soil depth. Roots of plants with
      functional phototropin-1 made fewer random turns and traveled further for a given
      length (higher efficiency) than roots of phot1 mutants. In dry (but not wet)
      soil, enhancement of root growth efficiency by phototropin-1 increased plant size
      at maturity. * Results indicate that phototropin-1 enhances performance under
      drought by mediating plastic increases in root growth efficiency near the soil
      surface.

PMID- 17176397
TI  - Stomatal behavior of ozone-sensitive and -insensitive coneflowers (Rudbeckia
      laciniata var. digitata) in Great Smoky Mountains National Park.
AB  - * Morphological and physiological attributes were assessed to elucidate the
      underlying mechanisms of ozone (O(3)) sensitivity in a highly sensitive species,
      cutleaf coneflower (Rudbeckia laciniata var. digitata). * Foliage at the same
      height in the canopy on paired O(3)-sensitive and -insensitive cutleaf
      coneflowers was assessed for level of foliar symptoms, stomatal density, stomatal
      responsiveness to dynamic changes in light and leaf-to-air vapor pressure deficit
      (VPD), steady-state responses to light and CO(2), intrinsic transpirational
      efficiency, and plant water balance. * There were no morphological differences
      between the sensitivity types that might have contributed to greater O(3) uptake
      in sensitive individuals. Stomata of sensitive plants were less responsive than
      those of insensitive plants to experimentally increased and decreased light
      intensities, and to increased VPD. O(3)-insensitive plants had greater intrinsic
      transpirational efficiencies, greater maximum assimilation rates under saturating
      CO(2) and light, and greater carboxylation rates. * Different physiological
      attributes vary independently within an individual plant, which collectively
      confer sensitivity or insensitivity to O(3) injury.

PMID- 17176398
TI  - Impact of temperature on the relationship between respiration and nitrogen
      concentration in roots: an analysis of scaling relationships, Q10 values and
      thermal acclimation ratios.
AB  - * The impact of nitrogen (N) supply on the temperature response of root
      respiratory O(2) uptake (R) was assessed in several herbaceous species grown in
      solution culture. Warm-grown (25 : 20 degrees C, day:night) plants differing in
      root N concentration were shifted to 13 : 8 degrees C for 7 d to cold-acclimate.
      * Log-log plots of root R vs root N concentration both showed that R increased
      with increasing tissue N concentration, irrespective of the growth temperature.
      Although the regression slopes of the log-log plots did not differ between the
      warm-grown and cold-acclimated plants, cold-acclimated plants did exhibit a
      higher y-axis intercept than their warm-grown counterparts. This suggests that
      cold acclimation of root R is not entirely dependent on cold-induced increases in
      tissue N concentration and that scaling relationships (i.e. regression equations
      fitted to the log-log plots) between root R and N concentration are not fixed. *
      No systematic differences were found in the short-term Q(10) (proportional change
      in R per 10 degrees C change in temperature), or degree of cold acclimation (as
      measured by the proportional difference between warm- and cold-acclimated roots)
      among roots differing in root N concentration. The temperature response of root R
      is therefore insensitive to tissue N concentration. * The insensitivity of Q(10)
      values and acclimation to tissue N concentration raises the possibility that root
      R and its temperature sensitivity can be predicted for a range of N supply
      scenarios.

PMID- 17176399
TI  - Reproductive and physiological responses to simulated climate warming for four
      subalpine species.
AB  - * The carbon costs of reproduction were examined in four subalpine herbaceous
      plant species for which number and size of flowers respond differently under a
      long-term infrared warming experiment. * Instantaneous measurements of gas
      exchange and an integrative model were used to calculate whole-plant carbon
      budgets and reproductive effort (RE). * Of the two species for which flowering
      was reduced, only one (Delphinium nuttallianum) exhibited higher RE under
      warming. The other species (Erythronium grandiflorum) flowers earlier when
      freezing events under warming treatment could have damaged floral buds. Of the
      two species for which flowering rates were not reduced, one (Helianthella
      quinquenervis) had higher RE, while RE was unaffected for the other (Erigeron
      speciosus). Each of these different responses was the result of a different
      combination of changes in organ size and physiological rates in each of the
      species. * Results show that the magnitude and direction of responses to warming
      differ greatly among species. Such results demonstrate the importance of
      examining multiple species to understand the complex interactions among
      physiological and reproductive responses to climate change.

PMID- 17176400
TI  - Shifts from competition to facilitation between a foundation tree and a pioneer
      shrub across spatial and temporal scales in a semiarid woodland.
AB  - * Theoretical and empirical research has supported the hypothesis that plant
      plant interactions change from competition to facilitation with increasing
      abiotic stress. However, the consistency of such changes has been questioned in
      arid and semiarid ecosystems. * During a drought in the semiarid south-western
      USA, we used observations and a field experiment to examine the interactions
      between juveniles of a foundation tree (Pinyon pine, Pinus edulis) and a common
      shrub (Apache plume, Fallugia paradoxa) in replicated areas of high and low
      stress. * The presence of F. paradoxa reduced P. edulis performance at low-stress
      sites, but had the opposite effect at high-stress sites. However, the intensity
      of the interactions depended on temporal variation in climate and age of P.
      edulis. Both above- and below-ground factors contributed to competition, while
      only above-ground factors contributed to facilitation. * These results support
      the hypothesis that interactions can change from competition to facilitation as
      abiotic stress increases in semiarid environments. A shift from competition to
      facilitation may be important for the recovery of P. edulis and other foundation
      species that have experienced large-scale mortality during recent droughts.

PMID- 17176402
TI  - Symbiotic nitrogen fixation in a tropical rainforest: 15N natural abundance
      measurements supported by experimental isotopic enrichment.
AB  - * Leguminous trees are very common in the tropical rainforests of Guyana. Here,
      species-specific differences in N(2) fixation capability among nodulating legumes
      growing on different soils and a possible limitation of N(2) fixation by a
      relatively high nitrogen (N) and low phosphorus (P) availability in the forest
      were investigated. * Leaves of 17 nodulating species and 17 non-nodulating
      reference trees were sampled and their delta(15)N values measured. Estimates of
      N(2) fixation rates were calculated using the (15)N natural abundance method. Pot
      experiments were conducted on the effect of N and P availability on N(2) fixation
      using the (15)N-enriched isotope dilution method. * Nine species showed estimates
      of > 33% leaf N derived from N(2) fixation, while the others had low or
      undetectable N(2) fixation rates. High N and low P availability reduced N(2)
      fixation substantially. * The results suggest that a high N and low P
      availability in the forest limit N(2) fixation. At the forest ecosystem level,
      N(2) fixation was estimated at c. 6% of total N uptake by the tree community. We
      conclude that symbiotic N(2) fixation plays an important role in maintaining high
      amounts of soil available N in undisturbed forest.

PMID- 17176401
TI  - Consequences of the overproduction of methyl jasmonate on seed production,
      tolerance to defoliation and competitive effect and response of Arabidopsis
      thaliana.
AB  - * Accumulation of methyl jasmonate (MeJA) after herbivore attack in plants is
      associated with the induction of defenses that can benefit fitness, but are
      costly to express; effects often explored using exogenous application of
      jasmonates. * Here I explored the consequences of the overexpression of MeJA on
      seed production, tolerance to defoliation and competitive effect and response,
      using a genotype of Arabidopsis thaliana that overexpresses jasmonic acid
      carboxyl methyltransferase (JMT) and contains threefold higher levels of MeJA
      than wild-type plants. * Without competition, JMT plants produced 37-40% less
      total seed mass than vector controls or wild-type plants, and had reduced seed
      germination. Defoliation reduced height more strongly in wild-type than in JMT
      plants, but reduced total seed production equally. In a competition experiment,
      the presence of a neighbor reduced fitness more strongly in wild-type than in JMT
      plants, but JMT plants exhibited dampened opportunity costs and benefits of
      induction with jasmonic acid of itself or its neighbor. This may have related to
      the higher constitutive expression but reduced inducibility of jasmonate-mediated
      defenses, including trypsin inhibitors, exhibited by JMT plants. * In natural
      plant populations, overexpression of MeJA-mediated responses should be beneficial
      to resistance to herbivores, pathogens and competitors, but is directly costly to
      fitness and probably constrains plasticity in response to changing environmental
      conditions.

PMID- 17176403
TI  - Burkholderia phymatum is a highly effective nitrogen-fixing symbiont of Mimosa
      spp. and fixes nitrogen ex planta.
AB  - * The ability of Burkholderia phymatum STM815 to effectively nodulate Mimosa
      spp., and to fix nitrogen ex planta, was compared with that of the known Mimosa
      symbiont Cupriavidus taiwanensis LMG19424. * Both strains were equally effective
      symbionts of M. pudica, but nodules formed by STM815 had greater nitrogenase
      activity. STM815 was shown to have a broader host range across the genus Mimosa
      than LMG19424, nodulating 30 out of 31 species, 21 of these effectively. LMG19424
      effectively nodulated only nine species. GFP-marked variants were used to
      visualise symbiont presence within nodules. * STM815 gave significant acetylene
      reduction assay (ARA) activity in semisolid JMV medium ex planta, but no ARA
      activity was detected with LMG19424. 16S rDNA sequences of two isolates
      originally from Mimosa nodules in Papua New Guinea (NGR114 and NGR195A)
      identified them as Burkholderia phymatum also, with nodA, nodC and nifH genes of
      NGR195A identical to those of STM815. * B. phymatum is therefore an effective
      Mimosa symbiont with a broad host range, and is the first reported beta-rhizobial
      strain to fix nitrogen in free-living culture.

PMID- 17176404
TI  - Carboxylate composition of root exudates does not relate consistently to a crop
      species' ability to use phosphorus from aluminium, iron or calcium phosphate
      sources.
AB  - * The relationship between carboxylate release from roots and the ability of the
      species to utilize phosphorus from sparingly soluble forms was studied by
      comparing Triticum aestivum, Brassica napus, Cicer arietinum, Pisum sativum,
      Lupinus albus, Lupinus angustifolius and Lupinus cosentinii. * Plants were grown
      in sand and supplied with 40 mg P kg(-1) in the sparingly soluble forms AlPO(4),
      FePO(4) or Ca(5)OH(PO(4))(3), or as soluble KH(2)PO(4); control plants received
      no P. * The ability to utilize sparingly soluble forms of P differed between
      forms of P supplied and species. Pisum sativum and C. arietinum did not access
      AlPO(4) or FePO(4) despite releasing carboxylates into the rhizosphere. * Species
      accessed different forms of sparingly soluble P, but no species was superior in
      accessing all forms. We conclude that a single trait cannot explain access to
      different forms of sparingly soluble P, and hypothesize that in addition to
      carboxylates, rhizosphere pH and root morphology are key factors.

PMID- 17176405
TI  - Reaction norms of life history traits in response to zinc in Thlaspi caerulescens
      from metalliferous and nonmetalliferous sites.
AB  - * We examined phenotypic plasticity of fitness components in response to zinc
      (Zn) in the Zn hyperaccumulator, Thlaspi caerulescens. * Two populations from Zn
      enriched soils (M) and two populations from normal soils (NM) were grown in pots
      at three Zn concentrations (0, 1000 and 8000 mg kg(-1) Zn), for an entire life
      cycle. Growth, Zn accumulation and fitness components were assessed. * Based on
      vegetative growth, M and NM populations had similar Zn tolerance at 1000 mg kg(
      1) Zn. However, reproductive output was markedly decreased in NM at 1000 and 8000
      mg kg(-1) Zn. In M populations, Zn did not affect fitness. However, low Zn status
      enhanced reproductive output in year 1 compared with year 2 and decreased
      survival after the first flowering season. * M populations are able to achieve
      equal fitness across a broad range of Zn concentrations in soil by different
      combinations of fecundity and longevity. No cost of higher tolerance was
      demonstrated in M populations. Reproductive traits appeared to be a more
      sensitive indicator of tolerance than vegetative growth.

PMID- 17176406
TI  - Life history variation in the heavy metal tolerant plant Thlaspi caerulescens
      growing in a network of contaminated and noncontaminated sites in southern
      France: role of gene flow, selection and phenotypic plasticity.
AB  - * Here we explore life history differences in a set of neighbouring metallicolous
      and nonmetallicolous populations of the heavy metal tolerant plant Thlaspi
      caerulescens. * We contrasted data from field observations and from a common
      garden experiment, in which soil zinc (Zn) concentration and light availability
      were manipulated, and data on microsatellite molecular variation. * The two
      ecotypes showed few differences in life history in the field, but large
      differences in their response to Zn concentration in the common garden. Soil
      toxicity affected most characters in nonmetallicolous plants, while it had no
      effect on metallicolous plants. The two ecotypes responded similarly to light.
      Genetic differentiation for quantitative characters between ecotypes contrasted
      with the absence of differentiation for microsatellites. Conversely, populations
      of the same ecotype showed similar responses to Zn, despite their high
      differentiation for molecular markers. * We conclude that divergent selection
      related to soil toxicity has had a predominant role in shaping life history
      differences between ecotypes, gene flow weakly opposing local adaptation despite
      geographical proximity.

PMID- 17176407
TI  - Focal plane array infrared imaging: a new way to analyse leaf tissue.
AB  - * Here, a new approach to macromolecular imaging of leaf tissue using a
      multichannel focal plane array (FPA) infrared detector was compared with the
      proven method of infrared mapping with a synchrotron source, using transverse
      sections of leaves from a species of Eucalyptus. * A new histological method was
      developed, ideally suited to infrared spectroscopic analysis of leaf tissue.
      Spatial resolution and the signal-to-noise ratio of the FPA imaging and
      synchrotron mapping methods were compared. * An area of tissue 350 microm(2)
      required approx. 8 h to map using the synchrotron technique and approx. 2 min to
      image using the FPA. The two methods produced similar infrared images, which
      differentiated all tissue types in the leaves according to their macromolecular
      chemistry. * The synchrotron and FPA methods produced similar results, with the
      synchrotron method having superior signal-to-noise ratio and potentially better
      spatial resolution, whereas the FPA method had the advantage in terms of data
      acquisition time, expense and ease of use. FPA imaging offers a convenient,
      laboratory-based approach to microscopic chemical imaging of leaves.

PMID- 17176408
TI  - [CME in the JDDG on a high level: the first German curricular literature
      continuing education in a model trial of the Nordrhein National Medical
      Association with the German Dermatologic Academy].

PMID- 17176409
TI  - [MEDLINE recognizes both the German print version and the English online version
      of JDDG!].

PMID- 17176410
TI  - Acne vulgaris--psychosomatic aspects.
AB  - More than a cosmetic nuisance, acne can produce anxiety, depression, and other
      psychological problems that affect patients' lives in ways comparable to life
      threatening or disabling diseases. Emotional problems due to the disease should
      be taken seriously and included in the treatment plan. A purely dermatological
      therapy by itself may not achieve its purpose. Even mild to moderate disease can
      be associated with significant depression and suicidal ideation, and psychologic
      change does not necessarily correlate with disease severity. Acne patients suffer
      particularly under social limitations and reduced quality of life. Psychological
      comorbidities in acne are probably greater than generally assumed. Attention
      should be paid to psychosomatic aspects especially if depressive-anxious
      disorders are suspected, particularly with evidence of suicidal tendencies, body
      dysmorphic disorders, or also in disrupted compliance.Therefore, patients who
      report particularly high emotional distress or dysmorphic tendencies due to the
      disease should be treated, if possible, by interdisciplinary therapy. The
      dermatologist should have some knowledge of the basics of psychotherapy and
      psychopharmacology, which sometimes must be combined with systemic and topical
      treatment of acne in conjunction with basic psychosomatic treatment.

PMID- 17176411
TI  - Calciphylaxis: no therapeutic concepts for a poorly understood syndrome?
AB  - Calciphylaxis is a very uncommon and severe disease which mainly appears in
      patients with chronic renal insufficiency. It presents with ischemia and necrosis
      of the skin, subcutaneous adipose tissue, muscles and rarely viscera. The
      pathogenetic mechanisms inducing calciphylaxis are for the most part unknown. The
      mortality rate of 80% in the first year is very high. Patients experience marked
      pain, recurrent infections and the constant risk of secondary sepsis. Even
      multidisciplinary therapeutic strategies are limited, although there are recent
      case reports providing promising new therapeutic options including sodium
      thiosulfate and cinacalcet. This review summarizes the important aspects of
      diagnosis, pathogenesis, prevention and the possible therapeutic strategies of
      this intriguing, rare and often fatal disease.

PMID- 17176412
TI  - IgA pemphigus--occurrence of anti-desmocollin 1 and anti-desmoglein 1 antibody
      reactivity in an individual patient.
AB  - BACKGROUND: IgA pemphigus is a rare pustular autoimmune disease with exclusive
      IgA anti-keratinocyte cell surface antibody reactivity. Two subtypes have been
      discerned: in the subcorneal pustular dermatosis type, desmocollin 1 has been
      identified as a targeted autoantigen, while in few cases of the intraepidermal
      neutrophilic type, IgA anti-desmoglein 1 or IgA anti-desmoglein 3 reactivity has
      been demonstrated. PATIENTS AND METHODS: A 48-year-old white male presented with
      generalized large confluent pustules. Skin pathology was assessed by histology
      and direct immunofluorescence analysis. IgG/IgA autoantibodies against desmoglein
      1/3 and desmocollin 1 were measured by ELISA and indirect immunofluorescence
      using desmocollin 1 cDNA-transfected COS7 cells, respectively. RESULTS:
      Histopathology revealed subcorneal pustules and direct immunofluorescence
      microscopy exclusively showed in vivo bound IgA with an intercellular pattern in
      the epidermis. Desmocollin 1 was identified as a target of IgA autoantibodies by
      indirect immunofluorescence microscopy utilizing desmocollin 1 cDNA-transfected
      COS7 cells. In addition, IgA anti-desmoglein 1 reactivity was demonstrated by
      ELISA. Neither IgA anti-desmoglein 3 nor IgG anti-desmoglein 1/3 autoantibodies
      were present. CONCLUSIONS: Both desmocollin 1 and desmoglein 1 were autoantigens
      in this patient with IgA pemphigus and a distinct clinical presentation. To our
      knowledge, this is the first IgA pemphigus case with dual autoantibody
      reactivity.

PMID- 17176413
TI  - Dirofilaria repens infection case in Hungary: a case report.
AB  - A 51-year-old female developed urticarial lesions of her right forearm which
      progressed into transient edema and subcutaneous swelling. Later a small
      infiltrated subcutaneous nodule also appeared and was removed in toto.
      Histopathological examination revealed the presence of Dirofilaria repens. This
      worm is the cause of an endemic zoonosis in the Mediterranean area. In the past
      decade many cases have been reported worldwide, but the condition appears rare in
      Hungary and skin findings have not been described.

PMID- 17176414
TI  - Clear differences in hand-held dermoscopes.
AB  - In order to correctly evaluate melanocytic and non-melanocytic skin tumors using
      a hand-held dermoscope, it is essential to have adequate magnification and
      illumination to allow the differential structures to be clearly seen. One example
      of a dysplastic compound melanocytic nevus and a thin malignant melanoma were
      examined with five different handheld dermoscopes (Heine Delta 10, Heine Delta
      20, Dermogenius and Dermlite Foto 37 with and without glass plate) in order to
      assess the image quality. The magnification was identical in all dermoscopes. In
      the newer dermoscopes (Heine Delta 20, Dermogenius and Dermlite Foto 37 with and
      without glass plate) the light sources were clearly improved, as now 6 or 24
      LEDs, respectively, are employed. This distinctly improved the image quality with
      regard to color and visible differential structures compared to the dermoscope
      (Heine Delta 10) with only one light source. Clear differences is assessing
      differential structures were seen in one dermoscope (Dermlite Foto 37 without
      glass plate). Using this dermoscope without any glass plate or liquid between the
      dermoscope and the skin, exophytic tumors were better visualized in a three
      dimensional fashion but fewer differential structures were seen.

PMID- 17176415
TI  - Diagnosis of syphilis: clinical and laboratory problems.

PMID- 17176416
TI  - [26-year-old male with urticarial papules].

PMID- 17176417
TI  - [The Muffin technique--an alternative to Mohs' micrographic surgery].

PMID- 17176419
TI  - [100 years of skin hospital Giessen: from the lupus hospice to the center of
      dermatology and andrology].
AB  - For one hundred years the skin hospital at the clinical center of Giessen
      University has been an important institution for patients with skin diseases. The
      hospital has not only been an address for patients to turn to but also a place of
      work and training for health personnel. Its profile has been especially
      established, formed and developed by the chairs of dermatology. Its development
      was strongly influenced by the treatment of lupus and STDs (sexually transmitted
      diseases). This is exemplary for the development of other German dermatology
      clinics.

PMID- 17176418
TI  - Tinea capitis.

PMID- 17176420
TI  - Nonconscious priming after 17 years: invulnerable implicit memory?
AB  - Individuals who saw pictures for 1 to 3 s in the laboratory were tested 17 years
      later by mail. Identification rates were significantly higher for fragments from
      these previously exposed targets than for novel fragments, whereas the same
      stimuli evoked no differences in control groups that had not been previously
      exposed to the pictures. Priming--the memorial advantage conferred by prior
      perceptual experience--was stable over the years (r= .51). Priming was
      dissociated from episodic memory, in that it was present even in subjects who
      reported no conscious recollection of their participation in the original
      laboratory session. These findings suggest that the perceptual representation
      system is an invulnerable memory system functioning below conscious awareness.

PMID- 17176421
TI  - Becoming a face expert.
AB  - Expertise in recognizing facial identity, and, in particular, sensitivity to
      subtle differences in the spacing among facial features, improves into
      adolescence. To assess the influence of experience, we tested adults and 8-year
      olds with faces differing only in the spacing of facial features. Stimuli were
      human adult, human 8-year-old, and monkey faces. We show that adults' expertise
      is shaped by experience: They were 9% more accurate in seeing differences in the
      spacing of features in upright human faces than in upright monkey faces. Eight
      year-olds were 14% less accurate than adults for both human and monkey faces
      (Experiment 1), and their accuracy for human faces was not higher for children's
      faces than for adults' faces (Experiment 2). The results indicate that
      improvements in face recognition after age 8 are not related to experience with
      human faces and may be related to general improvements in memory or in perception
      (e.g., hyperacuity and spatial integration).

PMID- 17176422
TI  - Can Florida become like the next Florida? When metaphoric comparisons fail.
AB  - Metaphors can be understood in either of two ways: via a comparison process or
      via a categorization process. What determines which process will be used?
      According to a recent variant of comparison theory, novel metaphors must be
      processed as comparisons; only conventional metaphors can be processed as
      categorizations. We argue that choice of process is determined not by
      conventionality, but instead by the semantic and referential properties of the
      metaphor itself. We identified a type of novel metaphor that is indeed understood
      more quickly as a comparison than as a categorization. We then generated variants
      of such metaphors to make comparison difficult and found that these new novel
      metaphors were understood more quickly as categorizations than as comparisons. We
      conclude that metaphors can be processed as categorizations from the start,
      depending on their semantic and referential properties.

PMID- 17176423
TI  - Hungry for money: the desire for caloric resources increases the desire for
      financial resources and vice versa.
AB  - This report attempts to provide an evolutionary explanation for humans'
      motivation to strive for money in present-day societies. We propose that people's
      desire for money is a modern derivate of their desire for food. In three studies,
      we show the reciprocal association between the incentive value of food and of
      money. In Study 1, hungry participants were less likely than satiated
      participants to donate to charity. In Study 2, participants in a room with an
      olfactory food cue, known to increase the desire to eat, offered less money in a
      give-some game compared with participants in a room free of scent. In Study 3,
      participants' desire for money affected the amount of M&M's they ate in a
      subsequent taste test, but only among participants who were not restricting their
      food intake in order to manage their weight.

PMID- 17176424
TI  - Choking and excelling under pressure.
AB  - Decrements in performance on cognitive tasks resulting from pressure to perform
      (i.e., choking) are thought to be caused by interference with the ability to use
      explicit strategies (the distraction theory). This view suggests that pressure
      should improve performance on tasks for which explicit strategies hamper
      performance. This hypothesis was tested by giving subjects one of two nearly
      identical learning tasks, a task that required learning a rule or one that
      required using a holistic information-integration strategy. Explicit rule use
      would hurt performance in the latter task. As predicted by the distraction
      theory, pressure decreased performance on the rule-based task but enhanced
      performance on the information-integration task.

PMID- 17176425
TI  - Color blindness and interracial interaction: playing the political correctness
      game.
AB  - Two experiments explored the ramifications of endorsing color blindness as a
      strategy for appearing unprejudiced. In Study 1, Whites proved adept at
      categorizing faces on the basis of race, but understated their ability to do so.
      In Study 2, Whites playing the Political Correctness Game--a matching task that
      requires describing other individuals--were less likely to use race as a
      descriptor when paired with a Black partner than when paired with a White
      partner, a strategy that impaired communication and performance. In addition,
      avoidance of race was associated with Whites making less eye contact with and
      appearing less friendly toward Black partners.

PMID- 17176426
TI  - Of two minds: forming and changing valence-inconsistent implicit and explicit
      attitudes.
AB  - Because different processes underlie implicit and explicit attitudes, we
      hypothesized that they are differentially sensitive to different kinds of
      information. We measured implicit and explicit attitudes over time, as different
      types of attitude-relevant information about a single attitude object were
      presented. As expected, explicit attitudes formed and changed in response to the
      valence of consciously accessible, verbally presented behavioral information
      about the target. In contrast, implicit attitudes formed and changed in response
      to the valence of subliminally presented primes, reflecting the progressive
      accretion of attitude object-evaluation pairings. As a consequence, when
      subliminal primes and behavioral information were of opposite valence, people
      formed implicit and explicit attitudes of conflicting valence.

PMID- 17176427
TI  - Accentuate the negative: the positive effects of negative acknowledgment.
AB  - Three studies investigated the capacity of negative acknowledgment, the admission
      of an unfavorable quality, to elicit relatively positive responses. In Study 1,
      an acknowledgment that a written paragraph was confusing led individuals to rate
      the paragraph as clearer than they did when no acknowledgment was offered. In
      Study 2, a foreign speaker was rated as possessing a clearer voice when he
      acknowledged his strong accent than when he did not. In Study 3, a hypothetical
      college applicant's acknowledgment of receiving less than stellar high school
      grades resulted in a more positive evaluation of those grades. The interpersonal
      risks and benefits of negative acknowledgment as an impression-management
      strategy are discussed.

PMID- 17176428
TI  - From affective valence to motivational direction: the frontal asymmetry of
      emotion revised.

PMID- 17176429
TI  - Pigeons see correspondence between objects and their pictures.
AB  - The extent to which nonhumans recognize the correspondence between static
      pictures and the objects they represent remains an interesting and controversial
      issue. Pictures displayed on computers are used extensively for research on
      behavioral and neural mechanisms of cognition in birds, yet attempts to show that
      birds recognize the objects seen in pictures have produced mixed and inconclusive
      results. We trained pigeons to discriminate between two identically colored but
      differently shaped three-dimensional objects seen directly or as pictures, and we
      found clear bidirectional transfer of the learned object discrimination. Transfer
      from objects to pictures occurred even when pigeons were trained with 12 views
      and only novel views of the objects were presented in transfer. This study
      provides the strongest evidence yet that pigeons can recognize the correspondence
      between objects and pictures.

PMID- 17176430
TI  - Attentional cues in real scenes, saccadic targeting, and Bayesian priors.
AB  - Performance finding a target improves when artificial cues direct covert
      attention to the target's probable location or locations, but how do predictive
      cues help observers search for objects in real scenes? Controlling for target
      detectability and retinal eccentricity, we recorded observers' first saccades
      during search for objects that appeared in expected and unexpected locations
      within real scenes. As has been found with synthetic images and cues, accuracy of
      first saccades was significantly higher when the target appeared at an expected
      location rather than an unexpected location. Observers' saccades with target
      absent images make it possible to distinguish two mechanisms that might mediate
      this effect: limited attentional resources versus differential weighting of
      information (Bayesian priors). Endpoints of first saccades in target-absent
      images were significantly closer to the expected than the unexpected locations, a
      result consistent with the differential-weighting model and inconsistent with
      limited resources being the sole mechanism underlying the effect.

PMID- 17176431
TI  - Humans rapidly estimate expected gain in movement planning.
AB  - We studied human movement planning in tasks in which subjects selected one of two
      goals that differed in expected gain. Each goal configuration consisted of a
      target circle and a partially overlapping penalty circle. Rapid hits into the
      target region led to a monetary bonus; accidental hits into the penalty region
      incurred a penalty. The outcomes assigned to target and penalty regions and the
      spatial arrangement of those regions were varied. Subjects preferred
      configurations with higher expected gain whether selection involved a rapid
      pointing movement or a choice by key press. Movements executed to select one of
      two goal configurations exhibited the same movement dynamics as pointing
      movements directed at a single configuration, and were executed with the same
      high efficiency. Our results suggest that humans choose near-optimal strategies
      when planning their movement, and can base their selection of strategy on a rapid
      judgment about the expected gain associated with possible movement goals.

PMID- 17176432
TI  - Are juvenile offenders extreme future discounters?
AB  - It has been the prevailing view that young offenders are more present oriented
      than their peers, but this view has little empirical basis other than the actions
      that have defined these youth as offenders. In the present study, we used a
      decision task with actual monetary consequences to assess the tendency of young
      offenders and a control group of high school students to discount the future. The
      young offenders were not significantly different from the students in discounting
      the future, even though the young offenders scored significantly higher on a
      sensation-seeking personality scale, were less likely to have lived with their
      fathers, and had changed schools more often. Young offenders and control
      participants were also similar in the extent to which they manifested a clear
      vision of the future by anticipating which future milestones would occur sooner,
      in a task pairing milestones with each other and with year markers.

PMID- 17176433
TI  - Attenuating the link between threatened egotism and aggression.
AB  - Research has found that narcissists behave aggressively when they receive a blow
      to their ego. The current studies examined whether narcissistic aggression could
      be reduced by inducing a unit relation between the target of aggression and the
      aggressor. Experimental participants were told that they shared either a birthday
      (Study 1) or a fingerprint type (Study 2) with a partner. Control participants
      were not given any information indicating similarity to their partner. Before
      aggression was measured, the partners criticized essays written by the
      participants. Aggression was measured by allowing participants to give their
      partner loud blasts of noise through a pair of headphones. In the control groups,
      narcissists were especially aggressive toward their partner. However,
      narcissistic aggression was completely attenuated, even under ego threat, when
      participants believed they shared a key similarity with their partner.

PMID- 17176434
TI  - Forgetting of prior remembering in persons reporting recovered memories of
      childhood sexual abuse.
AB  - Case studies of individuals reporting recovered memories of childhood sexual
      abuse suggest that some overestimate their prior forgetting of the abuse. People
      reporting recovered or continuous memories of childhood sexual abuse and control
      subjects reporting no history of abuse participated in two experiments examining
      this "forgot it all along" phenomenon. Participants in Experiment 1 were more
      likely to forget that they had previously recalled a studied item if they were
      cued to think of it differently on two recall tests than if they were cued to
      think of it in the same way on the two tests. This effect was stronger for
      recovered-memory participants than for continuous-memory and control
      participants. In Experiment 2, participants recalled autobiographical events
      three times over a period of 4 months. Much as in Experiment 1, they
      underestimated prior remembering when the events had been recalled in a different
      emotional frame (positive vs. negative) on the previous occasion. This
      underestimation was more pronounced for recovered-memory participants than for
      continuous-memory and control participants.

PMID- 17176435
TI  - ABO blood group and related antigens, natural antibodies and transplantation.
AB  - The current success rate of transplant surgery and immunosuppression has led to a
      demand for organs that has outstripped the supply. This has required
      investigation of alternate strategies. Therefore, allotransplantation across the
      ABO blood group barrier has commenced, and pig-to-human xenotransplantation is
      under consideration. The first immunological barrier to both these types of
      transplantation is the prevention of the antibody-mediated rejection. This
      rejection is a result of natural preformed antibodies circulating in the serum of
      the recipient binding to either ABO (for allo) or alpha-galactose (alpha-Gal)
      (for xeno) antigens expressed on the donor tissue. These antibodies recognise
      antigens that are, in both cases, carbohydrate molecules with the characteristic
      feature that the nonreducing terminal carbohydrate is either a Gal or N
      acetlygalactosamine residue in an alpha1,3 linkage. These epitopes are
      synthesised by closely related members of a single family of
      glycosyltransferases. This review discusses the carbohydrate antigens, the
      enzymes involved in their synthesis and the consequences of natural antibodies
      binding these antigens.

PMID- 17176437
TI  - Production, characterization, and applications of two novel monoclonal antibodies
      against human interleukin-28A.
AB  - Interleukin-28A (IL-28A) is a novel cytokine discovered in recent years and has
      been shown to have antiviral activity. In this study, IL-28A complementary DNA
      was inserted into prokaryotic expression vector pET-44 Ek/LIC. The Nus-S-His
      tagged IL-28A fusion protein was expressed in Escherichia coli BL21 (DE3) in the
      soluble fraction. The fusion protein was purified by S-protein agarose affinity
      chromatography, and the fusion tag was removed from recombinant IL-28A by
      cleavage with thrombin. To prepare specific monoclonal antibody against human IL
      28A, BALB/c mice were immunized with IL-28A, and hybridoma cell lines were
      obtained by fusing mouse spleen cells with myeloma NS-1 cells. Two strains of
      hybridoma cells, which produced the anti-human IL-28A antibodies 1B9 and 4B5 were
      obtained. They are IgM isotype and working in western blot analysis and enzyme
      linked immunosorbent assay. In the present study, it was shown for the first time
      that human umbilical vein endothelial cells treated with interferon-alpha and
      poly(I:C) express IL-28A protein assessed by flow cytometry and immunofluorescent
      staining techniques. Immunohistochemistry showed that macrophage-like cells in
      colon and lung tissue and alveolar epithelial cells in lung tissue contain IL
      28A, indicating a novel mechanism for both cell types to carry out their
      antivirus or antitumor functions.

PMID- 17176436
TI  - Identification of susceptibility and protective major histocompatibility complex
      haplotypes in canine diabetes mellitus.
AB  - Diabetes mellitus occurs spontaneously in dogs, which is believed to have an
      autoimmune component and to be a model of human latent autoimmune diabetes of
      adults (LADA). Some dog breeds (e.g. Samoyed) are particularly predisposed,
      whereas others (e.g. Boxer) are highly resistant. With the completion of the Dog
      Genome Assembly, comparative genomic studies of complex diseases in dogs,
      including diabetes, could provide an important investigative approach into such
      disorders. Type 1 diabetes in humans is strongly associated with major
      histocompatibility complex (MHC) class II polymorphisms. We have investigated
      whether canine dog leucocyte antigen (DLA) class II haplotypes are associated
      with diabetes. DNA from 460 cases and 1047 controls were genotyped for DLA-DRB1,
      DLA-DQA1 and DLA-DQB1 using sequence-based typing. Three DLA haplotypes,
      DRB1*009/DQA1*001/DQB1*008, DRB1*015/DQA1*0061/DQB1*023 and
      DRB1*002/DQA1*009/DQB1*001, were found at significantly increased frequency in
      cases with diabetes compared with controls. One DLA-DQ haplotype,
      DQA1*004/DQB1*013, was significantly reduced in cases with diabetes. Further
      analysis showed that DQA1 alleles carrying arginine at codon 55 of DQA1 were
      increased in dogs with diabetes. To our knowledge, this is the first report of a
      comparative study of MHC and diabetes in a non-rodent species. Since no
      laboratory model of LADA exists and dogs and humans share similar environments,
      further research into canine diabetes is warranted.

PMID- 17176438
TI  - Antibody responses to xenogenic antigens--a study in the mouse-to-rat system.
AB  - Antibodies play a crucial role in the rejection of an organ that has been
      transplanted between different animal species, i.e. xenotransplantation. In
      previous work, we have induced a state of humoral tolerance where mouse-to-rat
      heart grafts continued to beat under ciclosporine A monotherapy. Initially, a
      combined treatment with ciclosporine A and 15-deoxyspergualin was given. This
      state of tolerance could not be reproduced when the vascularised heart graft was
      replaced with a free tissue graft or xenogeneic blood transfusions. To gain
      further insight into the humoral response against mouse antigens, we studied the
      antibody production in naive rats and rats challenged with heart transplants,
      heart cells, mononuclear cells (MNC) and erythrocytes from mice. Rats not
      challenged with any mouse cells or organs had a moderate amount of antibodies
      targeted against mouse MNC as well as rosette-forming cells in the spleen
      targeted against mouse erythrocytes. A challenge with either mouse MNC or
      erythrocytes lead to immunisation with antibodies of both IgM and IgG subtype
      directed against both MNC and erythrocytes. Antibody titres against mouse
      erythrocytes in animals challenged with MNC were not detectable until day 7,
      whereas antibody titres against mouse MNC in animals challenged with erythrocytes
      were detected on day 1. Immunisation with mouse erythrocytes raised the titre of
      rosette-forming cells in the spleen compared with naive rats (P < 0.05). Our data
      indicate that different xenogeneic antigens in the mouse-to-rat system are shared
      between heart cells, MNC and erythrocytes; however, the immunisation patterns
      differ regarding the time when antibodies are first detected.

PMID- 17176439
TI  - No evidence of association of the MYO9B polymorphisms with celiac disease in the
      Spanish population.
AB  - Inconsistent results concerning the association of polymorphisms in the MYO9B
      gene with celiac disease (CD) have been recently published. This gene encodes a
      myosin with a guanosine-triphosphatase (GTPase)-activating protein domain for the
      Rho-family of small G proteins, which are involved in cytoskeleton remodeling and
      therefore potentially involved in intestinal permeability. Functional and
      positional reasons led us to investigate the role of MYO9B polymorphisms in the
      Spanish CD population. A case-control study, including 415 CD patients and 433
      ethnically matched healthy controls, and a familial study, including parents of
      145 of those CD patients, was performed. Six MYO9B variants previously associated
      with CD were analyzed: rs2305767, rs2279003, rs962917, rs1457092, rs2305765 and
      rs2305764. No MYO9B variants or MYO9B haplotypes were found associated with CD,
      either before or after stratification of the patients for the human leucocyte
      antigen (HLA)-DQ2-positive risk factor. The family study revealed no distorted
      transmission of the aforementioned MYO9B polymorphisms or haplotypes. Our results
      support a negligible influence of this gene on CD predisposition.

PMID- 17176440
TI  - The different expression patterns of interleukin-1 receptor antagonist in
      systemic lupus erythematosus.
AB  - The interleukin-1 receptor antagonist (IL1RN or IL-1Ra) is a natural antagonist
      of IL-1-beta. Using IL1RN as a possible marker in patients with systemic lupus
      erythematosus (SLE), we evaluated whether uIL1RN single nucleotide polymorphisms
      (SNPs) were associated with the pathogenesis of SLE in Taiwanese, and
      specifically whether IL1RN (rs315952) was significantly associated with end-stage
      renal disease. We examined IL1RN isoform expression patterns in patients with SLE
      to determine whether the expressions play a role in the pathogenesis of SLE. Both
      case-control and family-based association studies were used. For the case-control
      study, 104 patients with SLE and 97 normal controls were recruited, and for the
      family-based study, 11 families with SLE without renal disorder were recruited
      from the 104 patients with SLE. Eight IL1RN SNPs (rs2234678, rs2234679, rs315951,
      rs315952, rs419598, rs432014, rs447713, and rs451578) were selected for the
      family-based study. Reverse-transcriptase-polymerase chain reaction (RT-PCR) was
      used to determine the expression pattern of each isoform. Our results showed that
      IL1RN (rs315952) was significantly associated with SLE in patients without renal
      disorder in the family-based study, after disease stratification, but was not
      significantly associated with SLE in the case-control study. In the family-based
      study, the haplotype of IL1RN (AGCCTTAG) was significantly associated with SLE
      (chi2 = 11.714, P < 0.001). Using RT-PCR to determine the expression pattern of
      the IL1RN isoforms, we found different expression patterns between normal
      controls and patients with SLE, with an addition of IL1RN isoform4 or the low
      expression of IL1RN isoform1. We concluded that IL1RN and its isoforms were
      involved in the pathogenesis of SLE.

PMID- 17176441
TI  - Association of a common dog leucocyte antigen class II haplotype with canine
      primary immune-mediated haemolytic anaemia.
AB  - Immune-mediated haemolytic anaemia (IMHA) is the commonest immune-mediated
      disease of the dog, representing a major health concern to this species. The aim
      of this investigation was to determine whether genetic susceptibility to IMHA is
      associated with genes of the canine major histocompatibility complex (MHC; dog
      leucocyte antigen system, DLA). Samples were collected from 108 dogs with primary
      idiopathic, Coombs' positive IMHA. This diseased population was subdivided on the
      basis of Coombs' test results into two groups: 1) dogs with dominant warm
      reactive immunoglobulin (Ig) G haemagglutinins and (2) dogs with an additional or
      dominant cold-reactive IgM haemagglutinin. The DLA class II alleles and
      haplotypes of the diseased population were characterised, and these data were
      compared with those derived from a breed-matched control cohort and a much larger
      group of DLA-typed dogs. Two haplotypes were increased in the patient group: DLA
      DRB1*00601/DQA1*005011/DQB1*00701 (in the group with warm-reactive IgG
      haemagglutinins only) and DLA-DRB1*015/DQA1*00601/DQB1*00301 (in both groups, but
      more so in the group with cold-reactive IgM haemagglutinins). One haplotype, DLA
      DRB1*001/DQA1*00101/DQB1*00201, was decreased in the total patient group, but
      this decrease was limited to the warm-reactive IgG haemagglutinins group, and it
      was actually increased in the cold-reactive IgM haemagglutinins group. A second
      haplotype, DLA-DRB1*015/DQA1*00601/DQB1*02301, was also decreased in the total
      patient group, and this decrease was found in both subgroups. In addition, all
      haplotypes carrying DLA-DRB1*001 were significantly increased in the cold
      reactive IgM haemagglutinins group. When the overall patient group was divided on
      the basis of individual breeds with more than six animals represented, each of
      the haplotypes could be shown to be implicated in one of the breeds. Thus, it was
      apparent that different breeds had different MHC associations with canine IMHA,
      which is similar to the observation that different human ethnic groups can have
      different HLA associations with the same immune-mediated disease.

PMID- 17176442
TI  - Na, K ATPase beta3 subunit (CD298): association with alpha subunit and expression
      on peripheral blood cells.
AB  - Beta3 subunit is described as one of the Na, K ATPase subunits. Recently, we
      generated a monoclonal antibody (mAb), termed P-3E10. This mAb was shown to react
      with the Na, K ATPase beta3 subunit or CD298. By immunofluorescence analysis
      using mAb P-3E10, it was found that all peripheral blood leukocytes express Na, K
      ATPase beta3. The presence of beta3 subunit on leukocytes is not in a
      quantitative polymorphic manner. Upon phytohemagglutinin or phorbol myristate
      acetate activation, the expression level of the Na, K ATPase beta3 subunit on
      activated peripheral blood mononuclear cells was not altered in comparison with
      those of unstimulated cells. Red blood cells (RBCs) of healthy donors showed
      negative reactivity with mAb P-3E10. However, more than 80% of thalassemic RBCs
      showed positive reactivity. By immunoprecipitation, moreover, a protein band of
      55-65 kDa was precipitated from normal RBC membrane using mAb P-3E10. These
      results evidenced that the beta3 subunit of Na, K ATPase is expressed on RBC
      membrane but the epitope recognized by mAb P-3E10 is hidden in normal RBCs.
      Furthermore, we showed the association of beta3 subunit and alpha subunit of Na,
      K ATPase. This information is important for further understanding of the
      functional roles of this molecule.

PMID- 17176443
TI  - Identification of nine new HLA class I alleles in volunteers from the Singapore
      stem cell donor registries.
AB  - Based on unusual probe hybridization patterns, two human leukocyte antigen (HLA)
      A, five HLA-B, and two HLA-C alleles (A*240208, A*3211Q; B*1822, B*3938Q, B*4606,
      B*4607N, B*5139; Cw*0321, Cw*0734) were identified in individuals from the
      Singapore Bone Marrow Donor Program and Singapore Cord Blood Bank. Eight of the
      nine alleles encode amino acid substitutions altering the antigen-binding region
      including three alleles with changes altering a cysteine at codon 164 (A*3211Q,
      B*3938Q, B*4607N). This substitution either eliminates a key disulfide bond or
      results in a stop codon, both likely affecting the expression of the HLA
      molecules. Only one allele (A*240208) carries a synonymous substitution.

PMID- 17176444
TI  - Association of the maternal 14-bp insertion polymorphism in the HLA-G gene in
      women with recurrent spontaneous abortions.
AB  - Human leukocyte antigen (HLA)-G has been postulated as an important
      immunotolerant molecule in maintaining fetal-maternal relationship. Recent
      reports indicated that the 14-bp deletion/insertion polymorphism in exon 8 of HLA
      G gene influences HLA-G mRNA stability and isoform splicing patterns, thus
      modulating the levels of HLA-G expression. This might play an immunomodulatory
      role of HLA-G during implantation and pregnancy. In the present study, 109
      unrelated fertile control women and 79 women who had experienced recurrent
      spontaneous abortion (RSA) were genotyped for the 14-bp insertion/deletion
      polymorphism. No significant difference was observed in the distribution of 14-bp
      insertion/deletion genotype between controls and the RSA group. However, a
      greater number of 14-bp insertion alleles exist in the RSA group than in the
      controls.

PMID- 17176445
TI  - A novel HLA-A*11 allele, A*1118, identified by sequence-based typing.
AB  - The novel allele A*1118 shows three nucleotide differences with A*110101,
      resulting in three amino acid changes at positions 70, 74 and 90 of the mature
      protein.

PMID- 17176446
TI  - A new HLA-A*31 null allele, A*3114N.
AB  - A new HLA-A*31 null allele results from addition of an extra C near the beginning
      of exon 4 after a string of seven Cs.

PMID- 17176447
TI  - Routine HLA sequence-specific-oligonucleotide typing and confirming sequence
      based typing of a prospective bone marrow donor identified a novel B*27 allele,
      HLA-B*2734.
AB  - In this study, we report the identification of a new human leukocyte antigen-B
      allele in a sample that was tested in our routine typing for volunteer bone
      marrow donors. This novel allele officially named B*2734 was found in a female
      donor of Caucasoid origin (laboratory code 158567). The search for unrelated bone
      marrow donors was initiated by the Aktion Knochenmarkspende Bayern. In comparison
      with the closest related allele B*2707, B*2734 differs at two nucleotide
      positions, all located in exon 3, at position 412, 'A' in B*2707 is replaced by
      'G' and at position 486, 'G' is replaced by 'A' in the novel allele. The single
      nucleotide polymorphism at position 412 results in an amino acid substitution at
      codon 138. The amino acid asparagine is changed to aspartic acid in B*2734
      allele. The second nucleotide exchange is a silent mutation and codon 163 remains
      unaffected as ACG-->ACA, still codes for alanine.

PMID- 17176449
TI  - Sequencing of a new HLA-C allele, HLA-Cw*0742, with a novel HLA polymorphism at
      exon 3.
AB  - The new human leukocyte antigen (HLA)-C allele Cw*0742 was identified by sequence
      based typing in a Caucasian bone marrow donor. HLA-Cw*0742 differs from Cw*070201
      by a single nucleotide position at codon 113 (TAT --> TTT), giving rise to an
      amino acid substitution from Tyr to Phe.

PMID- 17176448
TI  - A new HLA-B allele, HLA-B*4068, identified in an Equatorian individual.
AB  - HLA-B*4068 shares exon 2 with HLA-B*4008 and exon 3 with HLA-B*4004.

PMID- 17176452
TI  - Nomenclature for factors of the HLA system, update July 2006.

PMID- 17176451
TI  - Identification of a novel HLA-DRB3 allele, DRB3*020205, by sequence-based typing.
AB  - The novel HLA allele DRB3*020205 (a synonymous G>T transition in exon 2) was
      identified in a European subject.

PMID- 17176450
TI  - A novel HLA-DRB1*11 allele, DRB1*1155, was found in a patient through routine
      DRB1 typing using sequence-specific primers (SSP) and confirmed by allele
      specific sequence-based typing.
AB  - In comparison with DRB1*1155 allele, DRB1*1103 differs at position 220/221, 'GC'
      is changed to 'CT', or DRB1*1125 differs at position 210/211, 'AG' is substituted
      with 'GA'. This results in a single amino acid exchange depending on the closest
      related allele investigated, whether DRB*1103 codon 74 alanine (GCG) is changed
      to leucine (CTG) or DRB1*1125 codon 71 arginine (GAG) is replaced with glutamic
      acid.

PMID- 17176453
TI  - Nomenclature for factors of the HLA system, update August 2006.

PMID- 17176454
TI  - Nomenclature for factors of the HLA system, update September 2006.

PMID- 17176455
TI  - The many routes to regulating mRNA translation.

PMID- 17176456
TI  - A follow up study on the efficacy of metadoxine in the treatment of alcohol
      dependence.
AB  - BACKGROUND: We carried out a three months follow-up study on the efficacy of
      metadoxine in a cohort of alcoholics admitted to the Alcohol misuse Long-term
      Treatment (ALT) Unit-University of Pisa (Italy). We analyzed the clinical data,
      psychometric tests and blood tests of 160 alcoholics on admission and after 3
      months of treatment. We compared 58 pts treated with metadoxine (MET) with 102
      pts who did not receive (NULL) any drug as an adjunct to the psycho-educational
      interventions provided by the ALT Unit. RESULTS: At follow-up, the patients in
      treatment with metadoxine showed a significant improvement in the rate of
      complete abstinence (44.8% vs. 21.6%; chi square: 8.45, df = 1, p < 0.0037).
      Furthermore, the number of drop-outs at three months of treatment was also
      significantly lower in the MET than in the NULL group (17% vs. 57%; chi square of
      23.22, df = 1, p < 0.001). CONCLUSION: Our findings support the use of metadoxine
      in the management of alcohol dependence. However, randomized clinical trials are
      necessary to confirm and replicate them. This study raises the importance of
      identifying new pharmacological compounds effective on the outcome of alcoholism
      in order to help patients to best adhere to treatment programs and to prevent the
      development of mental and physical complications due to chronic and heavy use of
      alcohol.

PMID- 17176457
TI  - An economic perspective on Malawi's medical "brain drain".
AB  - BACKGROUND: The medical "brain drain" has been described as rich countries
      "looting" doctors and nurses from developing countries undermining their health
      systems and public health. However this "brain-drain" might also be seen as a
      success in the training and "export" of health professionals and the benefits
      this provides. This paper illustrates the arguments and possible policy options
      by focusing on the situation in one of the poorest countries in the world,
      Malawi. DISCUSSION: Many see this "brain drain" of medical staff as wrong with
      developed countries exploiting poorer ones. The effects are considerable with
      Malawi facing high vacancy rates in its public health system, and with migration
      threatening to outstrip training despite efforts to improve pay and conditions.
      This shortage of staff has made it more challenging for Malawi to deliver on its
      Essential Health Package and to absorb new international health funding.Yet,
      without any policy effort Malawi has been able to demonstrate its global
      competitiveness in the training ("production") of skilled health professionals.
      Remittances from migration are a large and growing source of foreign exchange for
      poor countries and tend to go directly to households. Whilst the data for Malawi
      is limited, studies from other poor countries demonstrate the power of
      remittances in significantly reducing poverty. Malawi can benefit from the export
      of health professionals provided there is a resolution of the situation whereby
      the state pays for training and the benefits are gained by the individual
      professional working abroad. Solutions include migrating staff paying back
      training costs, or rich host governments remitting part of a tax (e.g. income or
      national insurance) to the Malawi government. These schemes would allow Malawi to
      scale up training of health professionals for local needs and to work abroad.
      SUMMARY: There is concern about the negative impacts of the medical "brain
      drain". However a closer look at the evidence for and against the medical "brain
      drain" in Malawi suggests that there are potential gains in managing medical
      migration to produce outcomes that are beneficial to individuals, households and
      the country. Finally we present several policy options.

PMID- 17176458
TI  - PageMan: an interactive ontology tool to generate, display, and annotate overview
      graphs for profiling experiments.
AB  - BACKGROUND: Microarray technology has become a widely accepted and standardized
      tool in biology. The first microarray data analysis programs were developed to
      support pair-wise comparison. However, as microarray experiments have become more
      routine, large scale experiments have become more common, which investigate
      multiple time points or sets of mutants or transgenics. To extract biological
      information from such high-throughput expression data, it is necessary to develop
      efficient analytical platforms, which combine manually curated gene ontologies
      with efficient visualization and navigation tools. Currently, most tools focus on
      a few limited biological aspects, rather than offering a holistic, integrated
      analysis. RESULTS: Here we introduce PageMan, a multiplatform, user-friendly, and
      stand-alone software tool that annotates, investigates, and condenses high
      throughput microarray data in the context of functional ontologies. It includes a
      GUI tool to transform different ontologies into a suitable format, enabling the
      user to compare and choose between different ontologies. It is equipped with
      several statistical modules for data analysis, including over-representation
      analysis and Wilcoxon statistical testing. Results are exported in a graphical
      format for direct use, or for further editing in graphics programs.PageMan
      provides a fast overview of single treatments, allows genome-level responses to
      be compared across several microarray experiments covering, for example, stress
      responses at multiple time points. This aids in searching for trait-specific
      changes in pathways using mutants or transgenics, analyzing development time
      courses, and comparison between species. In a case study, we analyze the results
      of publicly available microarrays of multiple cold stress experiments using
      PageMan, and compare the results to a previously published meta-analysis.PageMan
      offers a complete user's guide, a web-based over-representation analysis as well
      as a tutorial, and is freely available at http://mapman.mpimp
      golm.mpg.de/pageman/. CONCLUSION: PageMan allows multiple microarray experiments
      to be efficiently condensed into a single page graphical display. The flexible
      interface allows data to be quickly and easily visualized, facilitating
      comparisons within experiments and to published experiments, thus enabling
      researchers to gain a rapid overview of the biological responses in the
      experiments.

PMID- 17176459
TI  - Evidence of a linkage between matrilin-1 gene (MATN1) and idiopathic scoliosis.
AB  - BACKGROUND: In a previous study, a number of genes, associated with spine
      musculoskeletal deformity phenotypes in mouse and in synteny between mouse and
      man, were identified as candidate genes for IS. Among these genes, MATN1, which
      carries a polymorphic microsatellite marker within its sequence, was selected for
      a linkage analysis. MATN1 is localised at 1p35 and is mainly expressed in
      cartilage. The objective of this study was to assess a linkage disequilibrium
      between the matrilin-1 (MATN1) gene and the idiopathic scoliosis (IS). METHODS:
      The genetic study was conducted on a population of 81 trios, each consistent of a
      daughter/son affected by idiopathic scoliosis (IS) and both parents. In all trios
      components, the region of MATN1 gene containing the microsatellite marker was
      amplified by a polymerase chain reaction. The amplicons were analysed by a DNA
      sequencer-genotyper. The statistical linkage analysis was performed using the
      extended transmission/disequilibrium test. RESULTS: Three microsatellite
      polymorphisms, respectively consisting of 103 bp, 101 bp and 99 bp, were
      identified. ETDT evidenced a significant preferential transmission for the 103 bp
      allele (Chi-square = 5.058, df = 1, P = 0.024) CONCLUSION: The results suggest
      that the familial idiopathic scoliosis is associated to the MATN1 gene.

PMID- 17176460
TI  - Race-specific geography of prostate cancer incidence.
AB  - BACKGROUND: This study evaluated geographic distribution of race-specific
      prostate cancer incidence in Connecticut and Massachusetts. This cross-sectional
      analysis of census and cancer registry data included records of 29,040 Whites and
      1,647 African Americans diagnosed with incident prostate cancer between 1994 and
      1998. A spatial scan statistic was used to detect and test significance of the
      geographic variation in race-specific incidence rates within the two-state area.
      RESULTS: Significant geographic variation in age-adjusted incidence rates among
      both White and African American men was observed, with little overlap noted
      between distributions. Identified locations reflected patterns of residential
      segregation and socio-economic conditions. Among Whites, places with higher than
      expected incidence had higher socioeconomic status than places with lower than
      expected incidence. No discernable relationship between social indicators and
      rate variation among African Americans was evident. CONCLUSION: Differences in
      race-specific geographic distribution of prostate cancer incidence do not suggest
      a shared environmental etiology. Further study of genetic, behavioral and health
      care factors affecting the occurrence and/or reporting of the disease is
      warranted. This study highlights the need for race- and geographic-specific
      interventions to better control disease within at-risk communities and for on
      going analysis into social and contextual factors that contribute to observed
      disparities between African Americans and Whites in the occurrence of cancer.

PMID- 17176461
TI  - Effects of epidural lidocaine analgesia on labor and delivery: a randomized,
      prospective, controlled trial.
AB  - BACKGROUND: Whether epidural analgesia for labor prolongs the active-first and
      second labor stages and increases the risk of vacuum-assisted delivery is a
      controversial topic. Our study was conducted to answer the question: does lumbar
      epidural analgesia with lidocaine affect the progress of labor in our obstetric
      population? METHOD: 395 healthy, nulliparous women, at term, presented in
      spontaneous labor with a singleton vertex presentation. These patients were
      randomized to receive analgesia either, epidural with bolus doses of 1% lidocaine
      or intravenous, with meperidine 25 to 50 mg when their cervix was dilated to 4
      centimeters. The duration of the active-first and second stages of labor and the
      neonatal apgar scores were recorded, in each patient. The total number of vacuum
      assisted and cesarean deliveries were also measured. RESULTS: 197 women were
      randomized to the epidural group. 198 women were randomized to the single-dose
      intravenous meperidine group. There was no statistical difference in rates of
      vacuum-assisted delivery rate. Cesarean deliveries, as a consequence of fetal
      bradycardia or dystocia, did not differ significantly between the groups.
      Differences in the duration of the active-first and the second stages of labor
      were not statistically significant. The number of newborns with 1-min and 5-min
      Apgar scores less than 7, did not differ significantly between both analgesia
      groups. CONCLUSION: Epidural analgesia with 1% lidocaine does not prolong the
      active-first and second stages of labor and does not increase vacuum-assisted or
      cesarean delivery rate.

PMID- 17176462
TI  - On the visualization of universal degeneracy in the IMRT problem.
AB  - BACKGROUND: In general, the IMRT optimisation problem possesses many equivalent
      solutions. This makes it difficult to decide whether a result produced by an IMRT
      planning algorithm can be further improved, e.g. by adding more beams, or whether
      it is close to the globally best solution. RESULTS: It is conjectured that the
      curvature properties of the objective function around any globally optimum dose
      distribution are universal. This allows an assessment of optimality of dose
      distributions that are generated by different beam arrangements in a
      complementary manner to the objective function value alone. A tool to visualize
      the curvature structure of the objective function is devised. CONCLUSION: In an
      example case, it is demonstrated how the assessment of the curvature space can
      indicate the equivalence of rival beam configurations and their proximity to the
      global optimum.

PMID- 17176464
TI  - Child feeding and human rights.
AB  - BACKGROUND: The human right to adequate food needs to be interpreted for the
      special case of young children because they are vulnerable, others make the
      choices for them, and their diets are not diverse. There are many public policy
      issues relating to child feeding. DISCUSSION: The core of the debate lies in
      differences in views on the merits of infant formula. In contexts in which there
      is strong evidence and a clear consensus that the use of formula would be
      seriously dangerous, it might be sensible to adopt rules limiting its use.
      However, until there is broad consensus on this point, the best universal rule
      would be to rely on informed choice by mothers, with their having a clearly
      recognized right to objective and consistent information on the risks of using
      different feeding methods in their particular local circumstances. SUMMARY: The
      obligation of the state to assure that mothers are well informed should be viewed
      as part of its broader obligation to establish social conditions that facilitate
      sound child feeding practices. This means that mothers should not be compelled to
      feed in particular ways by the state, but rather the state should assure that
      mothers are supported and enabled to make good feeding choices.Thus, children
      should be viewed as having the right to be breastfed, not in the sense that the
      mother is obligated to breastfeed the child, but in the sense that no one may
      interfere with the mother's right to breastfeed the child. Breastfeeding should
      be viewed as the right of the mother and child together.

PMID- 17176463
TI  - Temporal order of evolution of DNA replication systems inferred by comparison of
      cellular and viral DNA polymerases.
AB  - BACKGROUND: The core enzymes of the DNA replication systems show striking
      diversity among cellular life forms and more so among viruses. In particular, and
      counter-intuitively, given the central role of DNA in all cells and the
      mechanistic uniformity of replication, the core enzymes of the replication
      systems of bacteria and archaea (as well as eukaryotes) are unrelated or
      extremely distantly related. Viruses and plasmids, in addition, possess at least
      two unique DNA replication systems, namely, the protein-primed and rolling circle
      modalities of replication. This unexpected diversity makes the origin and
      evolution of DNA replication systems a particularly challenging and intriguing
      problem in evolutionary biology. RESULTS: I propose a specific succession for the
      emergence of different DNA replication systems, drawing argument from the
      differences in their representation among viruses and other selfish replicating
      elements. In a striking pattern, the DNA replication systems of viruses infecting
      bacteria and eukaryotes are dominated by the archaeal-type B-family DNA
      polymerase (PolB) whereas the bacterial replicative DNA polymerase (PolC) is
      present only in a handful of bacteriophage genomes. There is no apparent
      mechanistic impediment to the involvement of the bacterial-type replication
      machinery in viral DNA replication. Therefore, I hypothesize that the observed,
      markedly unequal distribution of the replicative DNA polymerases among the known
      cellular and viral replication systems has a historical explanation. I propose
      that, among the two types of DNA replication machineries that are found in extant
      life forms, the archaeal-type, PolB-based system evolved first and had already
      given rise to a variety of diverse viruses and other selfish elements before the
      advent of the bacterial, PolC-based machinery. Conceivably, at that stage of
      evolution, the niches for DNA-viral reproduction have been already filled with
      viruses replicating with the help of the archaeal system, and viruses with the
      bacterial system never took off. I further suggest that the two other systems of
      DNA replication, the rolling circle mechanism and the protein-primed mechanism,
      which are represented in diverse selfish elements, also evolved prior to the
      emergence of the bacterial replication system. This hypothesis is compatible with
      the distinct structural affinities of PolB, which has the palm-domain fold shared
      with reverse transcriptases and RNA-dependent RNA polymerases, and PolC that has
      a distinct, unrelated nucleotidyltransferase fold. I propose that PolB is a
      descendant of polymerases that were involved in the replication of genetic
      elements in the RNA-protein world, prior to the emergence of DNA replication. By
      contrast, PolC might have evolved from an ancient non-templated polymerase, e.g.,
      polyA polymerase. The proposed temporal succession of the evolving DNA
      replication systems does not depend on the specific scenario adopted for the
      evolution of cells and viruses, i.e., whether viruses are derived from cells or
      virus-like elements are thought to originate from a primordial gene pool.
      However, arguments are presented in favor of the latter scenario as the most
      parsimonious explanation of the evolution of DNA replication systems. CONCLUSION:
      Comparative analysis of the diversity of genomic strategies and organizations of
      viruses and cellular life forms has the potential to open windows into the deep
      past of life's evolution, especially, with the regard to the origin of genome
      replication systems. When complemented with information on the evolution of the
      relevant protein folds, this comparative approach can yield credible scenarios
      for very early steps of evolution that otherwise appear to be out of reach.
      REVIEWERS: Eric Bapteste, Patrick Forterre, and Mark Ragan.

PMID- 17176465
TI  - TaxMan: a taxonomic database manager.
AB  - BACKGROUND: Phylogenetic analysis of large, multiple-gene datasets, assembled
      from public sequence databases, is rapidly becoming a popular way to approach
      difficult phylogenetic problems. Supermatrices (concatenated multiple sequence
      alignments of multiple genes) can yield more phylogenetic signal than individual
      genes. However, manually assembling such datasets for a large taxonomic group is
      time-consuming and error-prone. Additionally, sequence curation, alignment and
      assessment of the results of phylogenetic analysis are made particularly
      difficult by the potential for a given gene in a given species to be
      unrepresented, or to be represented by multiple or partial sequences. We have
      developed a software package, TaxMan, that largely automates the processes of
      sequence acquisition, consensus building, alignment and taxon selection to
      facilitate this type of phylogenetic study. RESULTS: TaxMan uses freely available
      tools to allow rapid assembly, storage and analysis of large, aligned DNA and
      protein sequence datasets for user-defined sets of species and genes. The user
      provides GenBank format files and a list of gene names and synonyms for the loci
      to analyse. Sequences are extracted from the GenBank files on the basis of
      annotation and sequence similarity. Consensus sequences are built automatically.
      Alignment is carried out (where possible, at the protein level) and aligned
      sequences are stored in a database. TaxMan can automatically determine the best
      subset of taxa to examine phylogeny at a given taxonomic level. By using the
      stored aligned sequences, large concatenated multiple sequence alignments can be
      generated rapidly for a subset and output in analysis-ready file formats. Trees
      resulting from phylogenetic analysis can be stored and compared with a reference
      taxonomy. CONCLUSION: TaxMan allows rapid automated assembly of a multigene
      datasets of aligned sequences for large taxonomic groups. By extracting sequences
      on the basis of both annotation and BLAST similarity, it ensures that all
      available sequence data can be brought to bear on a phylogenetic problem, but
      remains fast enough to cope with many thousands of records. By automatically
      assisting in the selection of the best subset of taxa to address a particular
      phylogenetic problem, TaxMan greatly speeds up the process of generating multiple
      sequence alignments for phylogenetic analysis. Our results indicate that an
      automated phylogenetic workbench can be a useful tool when correctly guided by
      user knowledge.

PMID- 17176466
TI  - Dramatic tumour response to pemetrexed single-agent in an elderly patient with
      malignant peritoneal mesothelioma: a case report.
AB  - BACKGROUND: To date, there is no standard treatment for unresectable malignant
      peritoneal mesothelioma; either best supportive care or systemic chemotherapy
      with palliative intent are accepted options. CASE PRESENTATION: Here, we report
      the case of a 79-year old patient with malignant peritoneal mesothelioma who was
      treated with pemetrexed single-agent and obtained an impressive long-lasting
      response. CONCLUSION: Single-agent pemetrexed is a treatment option for malignant
      peritoneal mesothelioma in selected elderly patients or in patients with unpaired
      performance status.

PMID- 17176467
TI  - Mariner mutagenesis of Brucella melitensis reveals genes with previously
      uncharacterized roles in virulence and survival.
AB  - BACKGROUND: Random gene inactivation used to identify cellular functions
      associated with virulence and survival of Brucella spp has relied heavily upon
      the use of the transposon Tn5 that integrates at G/C base pairs. Transposons of
      the mariner family do not require species-specific host factors for efficient
      transposition, integrate nonspecifically at T/A base pairs, and, at a minimum,
      provide an alternative approach for gene discovery. In this study, plasmid vector
      pSC189, containing both the hyperactive transposase C9 and transposon terminal
      inverted repeats flanking a kanamycin resistance gene, were used to deliver
      Himar1 transposable element into the B. melitensis genome. Conjugation was
      performed efficiently and rapidly in less than one generation in order to
      minimize the formation of siblings while assuring the highest level of genome
      coverage. RESULTS: Although previously identified groups or classes of genes
      required for virulence and survival were represented in the screen, additional
      novel identifications were revealed and may be attributable to the difference in
      insertion sequence biases of the two transposons. Mutants identified using a
      fluorescence-based macrophage screen were further evaluated using gentamicin
      based protection assay in macrophages, survival in the mouse splenic clearance
      model and growth in vitro to identify mutants with reduced growth rates.
      CONCLUSION: The identification of novel genes within previously described groups
      was expected, and nearly two-thirds of the 95 genes had not been previously
      reported as contributing to survival and virulence using random Tn5-based
      mutagenesis. The results of this work provide added insight with regard to the
      regulatory elements, nutritional demands and mechanisms required for efficient
      intracellular growth and survival of the organism.

PMID- 17176468
TI  - Empirical study of supervised gene screening.
AB  - BACKGROUND: Microarray studies provide a way of linking variations of phenotypes
      with their genetic causations. Constructing predictive models using high
      dimensional microarray measurements usually consists of three steps: (1)
      unsupervised gene screening; (2) supervised gene screening; and (3) statistical
      model building. Supervised gene screening based on marginal gene ranking is
      commonly used to reduce the number of genes in the model building. Various simple
      statistics, such as t-statistic or signal to noise ratio, have been used to rank
      genes in the supervised screening. Despite of its extensive usage, statistical
      study of supervised gene screening remains scarce. Our study is partly motivated
      by the differences in gene discovery results caused by using different supervised
      gene screening methods. RESULTS: We investigate concordance and reproducibility
      of supervised gene screening based on eight commonly used marginal statistics.
      Concordance is assessed by the relative fractions of overlaps between top ranked
      genes screened using different marginal statistics. We propose a Bootstrap
      Reproducibility Index, which measures reproducibility of individual genes under
      the supervised screening. Empirical studies are based on four public microarray
      data. We consider the cases where the top 20%, 40% and 60% genes are screened.
      CONCLUSION: From a gene discovery point of view, the effect of supervised gene
      screening based on different marginal statistics cannot be ignored. Empirical
      studies show that (1) genes passed different supervised screenings may be
      considerably different; (2) concordance may vary, depending on the underlying
      data structure and percentage of selected genes; (3) evaluated with the Bootstrap
      Reproducibility Index, genes passed supervised screenings are only moderately
      reproducible; and (4) concordance cannot be improved by supervised screening
      based on reproducibility.

PMID- 17176469
TI  - Management of environmental health issues for the 2004 Athens Olympic Games: is
      enhanced integrated environmental health surveillance needed in every day routine
      operation?
AB  - BACKGROUND: Management of environmental health issues is an integral part of
      public health systems. An active integrated environmental health surveillance and
      response system was developed for the Athens Olympics to monitor and prevent
      exposure to environmental hazards. The potential for permanent implementation of
      the program was examined. METHODS: The environmental health surveillance and
      response system included standardization, computerization and electronic
      transmission of data concerning environmental inspections of 17 site categories
      (restaurants, swimming pools etc) of public health interest, drinking and
      recreational water examinations and suggested corrective actions. The Olympic
      Planning Unit integrated and centrally managed data from 13 public health
      agencies, recommended, supervised and coordinated prompt corrective actions.
      Methods used to test the effectiveness of the program were the assessment of
      water quality test and inspection results trends over time using linear
      regression and epidemiological surveillance findings. RESULTS: Between January
      2003 and September the 30th, 2004, 196 inspectors conducted 8562 inspections,
      collected 5024 water samples and recommended 17 027 corrective actions. In 10
      cruise ships used as floating hotels inspectors conducted 10 full inspections, 2
      re-inspections, and 27 follow-up inspections. Unsatisfactory inspection results
      (r = 0.44, p < 0.0001) and positive water quality tests (r = 0.39, p < 0.001)
      presented an overall decrease trend over time. In August, 2003, an outbreak of
      salmonellosis was linked to a hotel restaurant which accommodated athletes during
      a test event. CONCLUSION: Lessons learned for future events include timely
      implementation and installation of communication processes, and rapid and
      coordinated response to unsatisfactory inspection results. Routine national
      programs need to adopt enhanced environmental health surveillance aimed at public
      health decision-making, but with a different perspective.

PMID- 17176470
TI  - Replication of the association of HLA-B7 with Alzheimer's disease: a role for
      homozygosity?
AB  - BACKGROUND: There are reasons to expect an association with Alzheimer's disease
      (AD) within the HLA region. The HLA-B & C genes have, however, been relatively
      understudied. A geographically specific association with HLA-B7 & HLA-Cw*0702 had
      been suggested by our previous, small study. METHODS: We studied the HLA-B & C
      alleles in 196 cases of 'definite' or 'probable' AD and 199 elderly controls of
      the OPTIMA cohort, the largest full study of these alleles in AD to date.
      RESULTS: We replicated the association of HLA-B7 with AD (overall, adjusted odds
      ratio = 2.3, 95% confidence interval = 1.4-3.7, p = 0.001), but not the
      previously suggested interaction with the epsilon4 allele of apolipoprotein E.
      Results for HLA-Cw*0702, which is in tight linkage disequilibrium with HLA-B7,
      were consistent with those for the latter. Homozygotes of both alleles appeared
      to be at particularly high risk of AD. CONCLUSION: HLA-B7 and HLA-Cw*0702 are
      associated with AD in the Oxford population. Because of the contradictions
      between cohorts in our previous study, we suggest that these results may be
      geographically specific. This might be because of differences between populations
      in the structure of linkage disequilibrium or in interactions with environmental,
      genetic or epigenetic factors. A much larger study will be needed to clarify the
      role of homozygosity of HLA alleles in AD risk.

PMID- 17176471
TI  - Expression of chemokine receptor CXCR4 in esophageal squamous cell and
      adenocarcinoma.
AB  - BACKGROUND: Prognosis of esophageal cancer is poor despite curative surgery. The
      chemokine receptor CXCR4 has been proposed to distinctly contribute to tumor
      growth, dissemination and local immune escape in a limited number of
      malignancies. The aim of our study was to evaluate the role of CXCR4 in tumor
      spread of esophageal cancer with a differentiated view of the two predominant
      histologic types--squamous cell and adenocarcinoma. METHODS: Esophageal cancer
      tissue samples were obtained from 102 consecutive patients undergoing esophageal
      resection for cancer with curative intent. The LSAB+ System was used to detect
      the protein CXCR4. Tumor samples were classified into two groups based on the
      homogeneous staining intensity. A cut-off between CXCR4w (= weak expression) and
      CXCR4s (= strong expression) was set at 1.5 (grouped 0-1.5 versus 2.0-3). Long
      term survival rates were calculated using life tables and the Kaplan-Meier
      method. Using the Cox's proportional hazards analysis, a model of survival
      prediction was established. RESULTS: The overall expression rate for CXCR4 in
      esophageal squamous cell carcinoma was 94.1%. Subdividing these samples, CXCR4w
      was found in 54.9% and CXCR4s in 45.1%. In adenocarcinoma, an overall expression
      rate of 89.1% was detected with a weak intensitiy in 71.7% compared to strong
      staining in 29.3% (p = 0.066 squamous cell versus adenocarcinoma). The Cox's
      proportional hazards analysis identified the pM-category with a hazard ratio (HR)
      of 1.860 (95% CI: 1.014-3.414) (p = 0.045), the histologic tumor type (HR: 0.334;
      95% CI: 0.180-0.618) (p = 0.0001) and the operative approach (transthoracic >
      transhiatal esophageal resection) (HR: 0.546; 95% CI: 0.324-0.920) (p = 0.023) as
      independent factors with a possible influence on the long-term prognosis in
      patients with esophageal carcinoma, whereas CXCR4 expression was statistically
      not significant (>0.05). CONCLUSION: Expression of the chemokine receptor CXCR4
      in esophageal cancer is of major relevance in both histologic entities--squamous
      cell and adenocarcinoma. Though with lack of statistical significance, strong
      CXCR4 expression revealed a poorer long-term prognosis following curative
      esophagectomy in both histologic subtypes. Thus, the exact biological functions
      of CXCR4 in terms of tumor dissemination of esophageal cancer is yet
      undetermined. Inhibition of esophageal cancer progression by CXCR4 antagonists
      might be a promising therapeutic option in the future.

PMID- 17176474
TI  - Recent trends in robot-assisted therapy environments to improve real-life
      functional performance after stroke.
AB  - Upper and lower limb robotic tools for neuro-rehabilitation are effective in
      reducing motor impairment but they are limited in their ability to improve real
      world function. There is a need to improve functional outcomes after robot
      assisted therapy. Improvements in the effectiveness of these environments may be
      achieved by incorporating into their design and control strategies important
      elements key to inducing motor learning and cerebral plasticity such as mass
      practice, feedback, task-engagement, and complex problem solving. This special
      issue presents nine articles. Novel strategies covered in this issue encourage
      more natural movements through the use of virtual reality and real objects and
      faster motor learning through the use of error feedback to guide acquisition of
      natural movements that are salient to real activities. In addition, several
      articles describe novel systems and techniques that use of custom and commercial
      games combined with new low-cost robot systems and a humanoid robot to embody the
      " supervisory presence" of the therapy as possible solutions to exercise
      compliance in under-supervised environments such as the home.

PMID- 17176473
TI  - PRMT6 diminishes HIV-1 Rev binding to and export of viral RNA.
AB  - BACKGROUND: The HIV-1 Rev protein mediates nuclear export of unspliced and
      partially spliced viral RNA through interaction with the Rev response element
      (RRE) by means of an arginine rich motif that is similar to the one found in Tat.
      Since Tat is known to be asymmetrically arginine dimethylated by protein arginine
      methyltransferase 6 (PRMT6) in its arginine rich motif, we investigated whether
      the Rev protein could act as a substrate for this enzyme. RESULTS: Here, we
      report the methylation of Rev due to a single arginine dimethylation in the N
      terminal portion of its arginine rich motif and the association of Rev with PRMT6
      in vivo. Further analysis demonstrated that the presence of increasing amounts of
      wild-type PRMT6, as well as a methylation-inactive mutant PRMT6, dramatically
      down-regulated Rev protein levels in concentration-dependent fashion, which was
      not dependent on the methyltransferase activity of PRMT6. Quantification of Rev
      mRNA revealed that attenuation of Rev protein levels was due to a
      posttranslational event, carried out by a not yet defined activity of PRMT6.
      However, no relevant protein attenuation was observed in subsequent
      chloramphenicol acetyltransferase (CAT) expression experiments that screened for
      RNA export and interaction with the RRE. Binding of the Rev arginine rich motif
      to the RRE was reduced in the presence of wild-type PRMT6, whereas mutant PRMT6
      did not exert this negative effect. In addition, diminished interactions between
      viral RNA and mutant Rev proteins were observed, due to the introduction of
      single arginine to lysine substitutions in the Rev arginine rich motif. More
      importantly, wild-type PRMT6, but not mutant methyltransferase, significantly
      decreased Rev-mediated viral RNA export from the nucleus to the cytoplasm in a
      dose-dependent manner. CONCLUSION: These findings indicate that PRMT6 severely
      impairs the function of HIV-1 Rev.

PMID- 17176475
TI  - Variations in cyclin D1 levels through the cell cycle determine the proliferative
      fate of a cell.
AB  - We present evidence that variations in cyclin D1 levels through the cell cycle
      are essential for continuing proliferation. Cyclin D1 levels must be high during
      G1 phase for a cell to initiate DNA synthesis, but then must be suppressed to low
      levels during S phase to allow for efficient DNA synthesis. This suppression
      during S phase is apparently regulated by cell cycle position alone and occurs
      automatically during each cell cycle. If the cell is to continue proliferating,
      cyclin D1 levels must be induced once again during G2 phase. This induction
      depends upon the activity of proliferative signaling molecules, and ensures that
      the extracellular environment continues to be conducive for growth. We propose
      that the suppression of cyclin D1 levels during each S phase ensures that the
      subsequent induction during G2 phase, and the resulting commitment to continuing
      proliferation, is closely linked to the cellular growth environment.

PMID- 17176476
TI  - Intelligent Bayes Classifier (IBC) for ENT infection classification in hospital
      environment.
AB  - Electronic Nose based ENT bacteria identification in hospital environment is a
      classical and challenging problem of classification. In this paper an electronic
      nose (e-nose), comprising a hybrid array of 12 tin oxide sensors (SnO2) and 6
      conducting polymer sensors has been used to identify three species of bacteria,
      Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Pseudomonas
      aeruginosa (P. aeruginosa) responsible for ear nose and throat (ENT) infections
      when collected as swab sample from infected patients and kept in ISO agar
      solution in the hospital environment. In the next stage a sub-classification
      technique has been developed for the classification of two different species of
      S. aureus, namely Methicillin-Resistant S. aureus (MRSA) and Methicillin
      Susceptible S. aureus (MSSA). An innovative Intelligent Bayes Classifier (IBC)
      based on "Baye's theorem" and "maximum probability rule" was developed and
      investigated for these three main groups of ENT bacteria. Along with the IBC
      three other supervised classifiers (namely, Multilayer Perceptron (MLP),
      Probabilistic neural network (PNN), and Radial Basis Function Network (RBFN))
      were used to classify the three main bacteria classes. A comparative evaluation
      of the classifiers was conducted for this application. IBC outperformed MLP, PNN
      and RBFN. The best results suggest that we are able to identify and classify
      three bacteria main classes with up to 100% accuracy rate using IBC. We have also
      achieved 100% classification accuracy for the classification of MRSA and MSSA
      samples with IBC. We can conclude that this study proves that IBC based e-nose
      can provide very strong and rapid solution for the identification of ENT
      infections in hospital environment.

PMID- 17176477
TI  - Secretion and properties of a hybrid Kluyveromyces lactis-Aspergillus niger beta
      galactosidase.
AB  - BACKGROUND: The beta-galactosidase from Kluyveromyces lactis is a protein of
      outstanding biotechnological interest in the food industry and milk whey
      reutilization. However, due to its intracellular nature, its industrial
      production is limited by the high cost associated to extraction and downstream
      processing. The yeast-system is an attractive method for producing many
      heterologous proteins. The addition of a secretory signal in the recombinant
      protein is the method of choice to sort it out of the cell, although
      biotechnological success is not guaranteed. The cell wall acting as a molecular
      sieve to large molecules, culture conditions and structural determinants present
      in the protein, all have a decisive role in the overall process. Protein
      engineering, combining domains of related proteins, is an alternative to take
      into account when the task is difficult. In this work, we have constructed and
      analyzed two hybrid proteins from the beta-galactosidase of K. lactis,
      intracellular, and its Aspergillus niger homologue that is extracellular. In
      both, a heterologous signal peptide for secretion was also included at the N
      terminus of the recombinant proteins. One of the hybrid proteins obtained has
      interesting properties for its biotechnological utilization. RESULTS: The highest
      levels of intracellular and extracellular beta-galactosidase were obtained when
      the segment corresponding to the five domain of K. lactis beta-galactosidase was
      replaced by the corresponding five domain of the A. niger beta-galactosidase.
      Taking into account that this replacement may affect other parameters related to
      the activity or the stability of the hybrid protein, a thoroughly study was
      performed. Both pH (6.5) and temperature (40 degrees C) for optimum activity
      differ from values obtained with the native proteins. The stability was higher
      than the corresponding to the beta-galactosidase of K. lactis and, unlike this,
      the activity of the hybrid protein was increased by the presence of Ni2+. The
      affinity for synthetic (ONPG) or natural (lactose) substrates was higher in the
      hybrid than in the native K. lactis beta-galactosidase. Finally, a structural
      model of the hybrid protein was obtained by homology modelling and the
      experimentally determined properties of the protein were discussed in relation to
      it. CONCLUSION: A hybrid protein between K. lactis and A. niger beta
      galactosidases was constructed that increases the yield of the protein released
      to the growth medium. Modifications introduced in the construction, besides to
      improve secretion, conferred to the protein biochemical characteristics of
      biotechnological interest.

PMID- 17176478
TI  - Leishmania infantum leishmaniasis in corticosteroid--treated patients.
AB  - BACKGROUND: The number of leishmaniasis cases associated with immunosuppression
      has increased regularly over the past 20 years. Immunosuppression related to HIV
      infection, immunosuppressive treatment, organ transplantation, and neoplastic
      diseases increases the risk for Leishmania-infected people to develop visceral
      illness. CASE PRESENTATION: Three cases of Leishmania infantum leishmaniasis in
      corticosteroid (CS)-treated patients are reported: an isolated lingual
      leishmaniasis in a farmer treated with CS for asthma, a severe visceral
      leishmaniasis associated with cutaneous lesions in a woman with myasthenia
      gravis, and a visceral involvement after cutaneous leishmaniasis in a man
      receiving CS. CONCLUSION: Physicians should recognise CS-treated patients as a
      population likely to be immune-suppressed. In immunodeficiency conditions,
      unusual forms of leishmaniasis can develop and foster the risk of a diagnostic
      delay and of poor response to therapy.

PMID- 17176479
TI  - Hypoxia and dehydroepiandrosterone in old age: a mouse survival study.
AB  - BACKGROUND: Survival remains an issue in pulmonary hypertension, a chronic
      disorder that often affects aged human adults. In young adult mice and rats,
      chronic 50% hypoxia (11% FIO2 or 0.5 atm) induces pulmonary hypertension without
      threatening life. In this framework, oral dehydroepiandrosterone was recently
      shown to prevent and reverse pulmonary hypertension in rats within a few weeks.
      To evaluate dehydroepiandrosterone therapy more globally, in the long term and in
      old age, we investigated whether hypoxia decreases lifespan and whether
      dehydroepiandrosterone improves survival under hypoxia. METHODS: 240 C57BL/6 mice
      were treated, from the age of 21 months until death, by normobaric hypoxia (11%
      FIO2) or normoxia, both with and without dehydroepiandrosterone sulfate (25 mg/kg
      in drinking water) (4 groups, N = 60). Survival, pulmonary artery and heart
      remodeling, weight and blood patterns were assessed. RESULTS: In normoxia,
      control mice reached the median age of 27 months (median survival: 184 days).
      Hypoxia not only induced cardiopulmonary remodeling and polycythemia in old
      animals but also induced severe weight loss, trembling behavior and high
      mortality (p < 0.001, median survival: 38 days). Under hypoxia however,
      dehydroepiandrosterone not only significantly reduced cardiopulmonary remodeling
      but also remarkably extended survival (p < 0.01, median survival: 126 days).
      Weight loss and trembling behavior at least partially remained, and polycythemia
      completely, the latter possibly favorably participating in blood oxygenation.
      Interestingly, at the dose used, dehydroepiandrosterone sulfate was detrimental
      to long-term survival in normoxia (p < 0.05, median survival: 147 days).
      CONCLUSION: Dehydroepiandrosterone globally reduced what may be called an age
      related frailty induced by hypoxic pulmonary hypertension. This interestingly
      recalls an inverse correlation found in the prospective PAQUID epidemiological
      study, between dehydroepiandrosterone blood levels and mortality in aged human
      smokers and former smokers.

PMID- 17176480
TI  - Many quality measurements, but few quality measures assessing the quality of
      breast cancer care in women: a systematic review.
AB  - BACKGROUND: Breast cancer in women is increasingly frequent, and care is complex,
      onerous and expensive, all of which lend urgency to improvements in care. Quality
      measurement is essential to monitor effectiveness and to guide improvements in
      healthcare. METHODS: Ten databases, including Medline, were searched
      electronically to identify measures assessing the quality of breast cancer care
      in women (diagnosis, treatment, followup, documentation of care). Eligible
      studies measured adherence to standards of breast cancer care in women diagnosed
      with, or in treatment for, any histological type of adenocarcinoma of the breast.
      Reference lists of studies, review articles, web sites, and files of experts were
      searched manually. Evidence appraisal entailed dual independent assessments of
      data (e.g., indicators used in quality measurement). The extent of each quality
      indicator's scientific validation as a measure was assessed. The American Society
      of Clinical Oncology (ASCO) was asked to contribute quality measures under
      development. RESULTS: Sixty relevant reports identified 58 studies with 143
      indicators assessing adherence to quality breast cancer care. A paucity of
      validated indicators (n = 12), most of which assessed quality of life, only
      permitted a qualitative data synthesis. Most quality indicators evaluated
      processes of care. CONCLUSION: While some studies revealed patterns of under-use
      of care, all adherence data require confirmation using validated quality
      measures. ASCO's current development of a set of quality measures relating to
      breast cancer care may hold the key to conducting definitive studies.

PMID- 17176481
TI  - HIV seroprevalence among participants at a Supervised Injection Facility in
      Vancouver, Canada: implications for prevention, care and treatment.
AB  - North America's first government sanctioned medically supervised injection
      facility (SIF) was opened during September 2003 in Vancouver, Canada. This was in
      response to a large open public drug scene, high rates of HIV and hepatitis C
      transmission, fatal drug overdoses, and poor health outcomes among the city's
      injection drug users. Between December 2003 and April 2005, a representative
      sample of 1,035 SIF participants were enrolled in a prospective cohort that
      required completing an interviewer-administered questionnaire and providing a
      blood sample for HIV testing. HIV infection was detected in 170/1007 (17%)
      participants and was associated with Aboriginal ethnicity (adjusted Odds Ratio
      [aOR], 2.70, 95% Confidence Interval [95% CI], 1.84-3.97), a history of borrowing
      used needles/syringes (aOR, 2.0, 95% CI, 1.37-2.93), previous incarceration (aOR,
      1.87, 95% CI, 1.11-3.14), and daily injection cocaine use (aOR, 1.42, 95% CI,
      1.00-2.03). The SIF has attracted a large number of marginalized injection drug
      users and presents an excellent opportunity to enhance HIV prevention through
      education, the provision of sterile injecting equipment, and a supervised
      environment to self-inject. In addition, the SIF is an important point of contact
      for HIV positive individuals who may not be participating in HIV care and
      treatment.

PMID- 17176482
TI  - Differential expression profiling between the relative normal and dystrophic
      muscle tissues from the same LGMD patient.
AB  - BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a group of heterogeneous
      muscular disorders with autosomal dominant and recessive inheritance, in which
      the pelvic or shoulder girdle musculature is predominantly or primarily involved.
      Although analysis of the defective proteins has shed some light onto their
      functions implicated in the etiology of LGMD, our understanding of the molecular
      mechanisms underlying muscular dystrophy remains incomplete. METHODS: To give
      insight into the molecular mechanisms of AR-LGMD, we have examined the
      differentially expressed gene profiling between the relative normal and
      pathological skeletal muscles from the same AR-LGMD patient with the differential
      display RT-PCR approach. The research subjects came from a Chinese AR-LGMD family
      with three affected sisters. RESULTS: In this report, we have identified 31 known
      genes and 12 unknown ESTs, which were differentially expressed between the
      relative normal and dystrophic muscle from the same LGMD patient. The expression
      of many genes encoding structural proteins of skeletal muscle fibers (such as
      titin, myosin heavy and light chains, and nebulin) were dramatically down
      regulated in dystrophic muscles compared to the relative normal muscles. The
      genes, reticulocalbin 1, kinectin 1, fatty acid desaturase 1, insulin-like growth
      factor binding protein 5 (IGFBP5), Nedd4 family interacting protein 1 (NDFIP1),
      SMARCA2 (SWI/SNF related, matrix associated, actin dependent regulator of
      chromatin, subfamily a, member 2), encoding the proteins involved in signal
      transduction and gene expression regulation were up-regulated in the dystrophic
      muscles. CONCLUSION: The functional analysis of these expression-altered genes in
      the pathogenesis of LGMD could provide additional information for understanding
      possible molecular mechanisms of LGMD development.

PMID- 17176483
TI  - The reliability of the Bad Sobernheim Stress Questionnaire (BSSQbrace) in
      adolescents with scoliosis during brace treatment.
AB  - BACKGROUND: A new instrument to assess stress scoliosis patients have whilst
      wearing their brace has been developed. Aim of this study was to test the
      reliability of this new instrument. METHODS: Eight questions are provided
      focussing on this topic only, including two questions to test the credibility. A
      max. score of 24 can be achieved (from 0 for most stress to 24 for least stress).
      We have proposed a subdivision of the score values as follows: 0-8 (strong
      stress), 9-16 (medium stress) and 17-24 (little stress).85 patients were invited
      to take part in this study and to complete the BSSQbrace questionnaire twice,
      once at the first presentation and a second after a further three days.62
      patients with an average age of 14,5 years and an average Cobb angle of 40
      degrees returned their fully completed questionnaires. RESULTS: The average
      stress value was 12,5/24 at the first measurement and 12,4/24 at the second
      measurement. Ceiling value was 23; floor value 2. The average stress value was
      12,5 / 24 at the first measurement and 12,4 / 24 at the second measurement (from
      0 for most stress to 24 for least stress). Ceiling value was 23; floor value 2.
      There was a correlation of 0,88 (Intraclass Correlation Coefficient) between the
      values of the two measurements. Cronbach alpha was 0, 97. CONCLUSION: The
      BSSQbrace questionnaire is reliable with good internal consistency and
      reproducibility. It can be used to measure the coping strategies a patient uses
      and the impairment a patient feels to have, whilst wearing a brace.

PMID- 17176484
TI  - Xenopus Dab2 is required for embryonic angiogenesis.
AB  - BACKGROUND: The molecular mechanisms governing the formation of the embryonic
      vascular system remain poorly understood. Here, we show that Disabled-2 (Dab2), a
      cytosolic adaptor protein, has a pivotal role in the blood vessel formation in
      Xenopus early embryogenesis. RESULTS: Xenopus Disabled-2 (XDab2) is spatially
      localized to the blood vessels including the intersomitic veins (ISV) in early
      embryos. Both antisense morpholino oligonucleotide (MO)-mediated knockdown and
      overexpression of XDab2 inhibit the formation of ISV, which arise from
      angiogenesis. In addition, we found that activin-like signaling is essential for
      this angiogenic event. Functional assays in Xenopus animal caps reveal that
      activin-like signals induce VEGF expression and this induction can be inhibited
      by XDab2 depletion. However, XDab2 MO has no effects on the induction of other
      target genes by activin-like signals. Furthermore, we show that the disruption of
      the sprouting ISV in XDab2-depleted embryos can be rescued by coexpression of
      VEGF. CONCLUSION: Taking together, we suggest that XDab2 regulates the embryonic
      angiogenesis by mediating the VEGF induction by activin-like signaling in Xenopus
      early development.

PMID- 17176486
TI  - Chorionic gonadotropin: a narrative of its identification and origin and the role
      of Georgeanna Seegar Jones.
AB  - The following article on the history of human chorionic gonadotropin is
      interesting on several levels. I hope that you will enjoy the first-hand
      description of the events surrounding the discovery of site of origin of this
      important pregnancy-related hormone as told by Dr. Howard Jones Jr., husband of
      the late Georgeanna Seegar Jones. They were both editors of the SURVEY for more
      than 25 years. In today's world of microarray and PCR technology it is fun to
      hear about the progress of science using tissue culture and mouse assays. But
      this story is also about the progress we have made on the human level. At a time
      when well over 50% of the residents in Obstetrics and Gynecology are women, it is
      astounding to think that in 1938 Mom's name would have been listed as "G. Emory
      Seegar" on this important paper because it was felt that the paper would not be
      accepted for publication if one of the authors was a woman!

PMID- 17176485
TI  - Differentiation-specific action of orphan nuclear receptor NR5A1 (SF-1):
      transcriptional regulation in luteinizing bovine theca cells.
AB  - BACKGROUND: The orphan nuclear receptor NR5A1 (steroidogenic factor-1, SF-1) is a
      master regulator of tissue-specific gene expression in reproductive and
      steroidogenic tissues. Two activating functions, AF-1 and AF-2, have been
      described to function in a cooperative manner to recruit transcriptional
      coactivators to the promoter regions of NR5A1-controlled genes. METHODS: The role
      of the NR5A1 activating functions AF-1 and AF-2 was studied in primary bovine
      theca cells. Bovine theca cells were infected with recombinant adenovirus vectors
      over-expressing wild-type NR5A1 or NR5A1 mutants, in which one of the activating
      functions of this orphan nuclear receptor had been impaired. Under different
      culture conditions, theca cell-specific transcript levels were measured by
      reverse transcription and real-time PCR. RESULTS: Under culture conditions
      optimized for cell growth, transcriptional up-regulation of CYP11A1 (P450 side
      chain-cleavage enzyme) and INSL3 (Insulin-like factor 3, Relaxin-like factor
      (RLF)) was found to be dependent on the presence of NR5A1 carrying an intact AF
      2. Under conditions inducing luteal differentiation of theca cells, CYP11A1 and
      STAR (Steroidogenic acute regulatory protein) were up-regulated by the action of
      luteinizing hormone (LH), whereas the differentiation-specific up-regulation of
      INSL3 was suppressed by LH in luteinizing theca cells. Inhibition of insulin- or
      IGF1- (insulin-like growth factor I) dependent signal transduction by the RAF1
      kinase inhibitor GW5074 and the mitogen-activated protein kinase kinase inhibitor
      PD98059 resulted in the finding that RAF1 kinase inhibition was able to
      counteract the LH-dependent regulation of NR5A1-controlled genes, whereas
      inhibition of the mitogen-activated protein kinase (MAP kinase) pathway did not
      have any significant effect. CONCLUSION: The regulation of the three NR5A1
      controlled genes CYPA11, STAR, and INSL3 in luteinizing theca cells apparently is
      not dependent on NR5A1 activating functions AF-1 or AF-2. Activation of AF-1 here
      even appears to have an impairing effect on NR5A1 transcriptional activity,
      implying that up-regulation of NR5A1-controlled genes uses a different pathway.
      Our results might be explained by the possible existence of an interconnection
      between the RAF1 kinase and the cyclic AMP-protein kinase A pathway. Such a non
      classical regulatory pathway might play an important role in the control of gene
      expression in reproductive and steroidogenic tissues.

PMID- 17176487
TI  - Lyme disease in pregnancy: case report and review of the literature.
AB  - Lyme disease is the most common vector-borne disease in the United States. A
      number of other spirochetal diseases, if contracted in pregnancy, have been shown
      to cause fetal harm and there is concern over a similar effect with gestational
      borreliosis. Previously published individual case reports have suggested a
      possible association between gestational borreliosis and adverse pregnancy
      outcome; however, no specific pattern of teratogenicity has been shown, and a
      causal relationship has never been proven. In addition, larger epidemiological
      and serological series have consistently failed to demonstrate an increased risk
      to pregnant women who develop Lyme disease if they receive appropriate
      antimicrobial therapy. We describe a favorable outcome in a 42-year-old woman who
      developed Lyme disease in the third trimester and was treated with a full course
      of oral amoxicillin. In addition, we offer a review of the relevant literature
      regarding Lyme disease and pregnancy. The appropriate investigation and
      management of a woman with gestational borreliosis are discussed. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES:
      After completion of this article, the reader should be able to recall that Lyme
      disease is not an uncommon disease during pregnancy and can occur in states
      outside of the Northeast, explain that the diagnosis is made clinically and may
      be confirmed by laboratory tests, state that treatment is recommended during
      pregnancy, and summarize that there is no consistent data of adverse fetal
      effects even though the placenta is infected.

PMID- 17176488
TI  - Ehlers-Danlos syndrome: insights on obstetric aspects.
AB  - Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue
      disorders characterized by joint hypermobility, skin hyperelasticity, tissue
      fragility, easy bruising, and poor healing of wounds. The clinical manifestations
      vary depending on the type of disease. The syndrome may be associated with a
      number of pregnancy and peripartum complications. Because of the multiorgan
      involvement and varied presentation of this disease, no uniform or routine
      obstetric and anesthetic recommendations can be made for the perinatal care of
      these patients. We present a review of the literature on EDS with emphasis on the
      obstetric, anesthetic, and perinatal consequences. We also report our experience
      with this syndrome: an uneventful term vaginal delivery in a 32-year-old woman
      diagnosed with hypermobility type of EDS. TARGET AUDIENCE: Obstetricians &
      Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this
      article, the reader should be able to recall the potentially severe nature of
      Ehlers-Danlos Syndrome (EDS) in both pregnant and nonpregnant patients, summarize
      the wide range of signs and symptoms and its genetic inheritance, and explain the
      difficulty in recommending obstetric and anesthesia procedures to avoid
      complications.

PMID- 17176489
TI  - Fertility preservation options for women with malignancies.
AB  - Cancer is not rare in younger women. There has been a remarkable improvement in
      the survival rates due to progress in cancer treatment. The necessary treatment
      for most of the common cancer types occurring in younger women implies either
      removal of the reproductive organs or cytotoxic treatment that could partially or
      definitively affect reproductive function. Early loss of ovarian function not
      only puts the patients at risk for menopause-related complications at a very
      young age, but is also associated with loss of fertility. Further, women in the
      western hemisphere have been delaying initiation of childbearing to later in
      life. The results of these changes have led to an increase in patients facing the
      risk of premature ovarian failure, and therefore seeking help in preserving their
      fertility. This increase in demand has resulted in a proliferation of techniques
      to preserve fertility. Indeed, the number of options is increasing; some are more
      established procedures, such as embryo cryopreservation, and some are still
      experimental, such as ovarian cryopreservation. Because of the variations in type
      and dose of chemotherapy, the type of cancer, the time available before onset of
      treatment, the patient's age and the partner status, each case is unique and
      requires a different strategy of fertility preservation. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader should be able to recall the potential
      early loss of ovarian function secondary to radiotherapy and/or chemotherapy for
      cancer at a young age; explain the increasing demands for fertility preservation;
      and summarize the limited number of proven, safe, and efficacious methods.

PMID- 17176490
TI  - Attraction behaviour of three entomopathogenic nematode species towards infected
      and uninfected hosts.
AB  - Entomopathogenic nematode infective juveniles are likely to encounter both
      uninfected and infected insects and host quality depends on the stage of the
      infection. We hypothesized that nematode response to infected hosts will change
      over the course of an infection. Here, we tested this hypothesis by focusing on
      the influence of host infection status on long-range attraction to host volatile
      cues. The attraction response of 3 nematode species (Steinernema carpocapsae, S.
      glaseri and S. riobrave) with different foraging strategies to infected and
      uninfected insects (Galleria mellonella and Tenebrio molitor) was tested at 24 h
      intervals from start of infection to emergence of infective juveniles from
      depleted host. As expected, based on their foraging strategies, S. carpocapsae
      was not very responsive to hosts, S. glaseri was highly responsive and S.
      riobrave was intermediate. Generally, the level of attraction did not change with
      time after infection and was similar between infected and uninfected hosts. An
      exception was S. glaseri infected T. molitor, which tended to be less attractive
      to S. glaseri than uninfected hosts. These results suggest that any influence of
      host infection status on infection behaviour is occurring at subsequent steps in
      the host-infection process than host attraction, or involves non-volatile cues.

PMID- 17176491
TI  - Association between a polymorphism in the promoter region of the TPH2 gene and
      the personality trait of harm avoidance.
AB  - In a genetic association study the role of the -703 G/T (rs4570625) polymorphism,
      located in the promoter region of the tryptophan hydroxylase 2 gene (TPH2), in
      personality traits was investigated in a sample of 404 healthy Caucasian
      subjects. A significant association between harm avoidance (HA), a trait related
      to anxiety, and the -703 G/T polymorphism was detected supporting the findings by
      Gutknecht and colleagues.

PMID- 17176493
TI  - The armamentarium of treatments for bipolar disorder: a review of the literature.
AB  - To assess current pharmacotherapeutic options for bipolar disorder, with
      particular emphasis on the use of antipsychotic agents, Medline and EMBASE were
      searched between January 1980 and December 2005 using the keywords
      "schizoaffective disorder" and "bipolar disorder", combined with various
      antidepressants, antipsychotics, lithium or other mood stabilizers. English
      language articles, review articles and original research articles were reviewed.
      Most data are available for the "mood stabilizers" lithium and valproate.
      However, these agents have important limitations regarding their tolerability and
      efficacy in certain groups. Newer anticonvulsants, especially lamotrigine, have
      demonstrated efficacy across mood-symptom domains. Antidepressants are not
      generally favoured as monotherapy in patients with bipolar depression or
      schizoaffective disorder, due to their potential to induce switching to manic
      states. However, data are emerging for the efficacy of selective serotonin
      reuptake inhibitors for bipolar depression in combination with atypical
      antipsychotics. Atypical antipsychotics may also be used as monotherapy or in
      conjunction with mood stabilizers for the treatment of acute mania and for
      continuing maintenance therapy. The choice of antipsychotic may be influenced by
      the therapeutic situation; formulations that facilitate administration in the
      acute scenario can provide rapid tranquillization, whereas those that enhance
      compliance may have a place in maintenance therapy. Our results suggest a growing
      role for atypical antipsychotics in the treatment of bipolar disorder and further
      data are anticipated.

PMID- 17176492
TI  - Tryptophan hydroxylase-2 gene variation influences personality traits and
      disorders related to emotional dysregulation.
AB  - Variation in the tryptophan hydroxylase-2 gene (TPH2) coding for the rate
      limiting enzyme of serotonin (5-HT) synthesis in the brain modulates responses of
      limbic circuits to emotional stimuli and has been linked to a spectrum of
      clinical populations characterized by emotional dysregulation. Here, we tested a
      set of common single nucleotide polymorphisms (SNPs) in and downstream of the
      transcriptional control region of TPH2 for association with personality traits
      and with risk for personality disorders in two cohorts comprising of 336 healthy
      individuals and 420 patients with personality disorders. Personality dimensions
      were assessed by the Tridimensional Personality Questionnaire (TPQ) and the
      revised NEO Personality Inventory (NEO-PI-R). Personality disorders were
      diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to
      clusters A, B, and C. Individual SNP and haplotype analyses revealed significant
      differences in genotype frequencies between controls and cluster B as well as
      cluster C patients, respectively. In both patient groups, we observed
      overrepresentation of T allele carriers of a functional polymorphism in the
      upstream regulatory region of TPH2 (SNP G-703T, rs4570625) which was previously
      shown to bias responsiveness of the amygdala, a structure critically involved in
      emotionality. Furthermore, significant effects of TPH2 variants on anxiety
      related traits defined primarily by the TPQ Harm Avoidance were found in healthy
      individuals. The results link potentially functional TPH2 variants to personality
      traits related to emotional instability as well as to cluster B and cluster C
      personality disorders. These findings implicate alterations of 5-HT synthesis in
      emotion regulation and confirm TPH2 as a susceptibility and/or modifier gene of
      affective spectrum disorders.

PMID- 17176495
TI  - All patients with suspected dementia should be scanned at least once with CT or
      MRI.

PMID- 17176496
TI  - Neuroimaging should not be a routine investigation in all cases of suspected
      dementia.

PMID- 17176497
TI  - Introduction: for debate: should neuroimaging be a routine investigation in all
      cases of suspected dementia?

PMID- 17176498
TI  - Current prevalence of hepatitis delta virus (HDV) infection and the range of HDV
      genotypes in Lebanon.
AB  - Recently the prevalence of hepatitis B virus (HBV) genotypes and the association
      between these genotypes and the clinical status of HBV-infected patients were
      recently investigated in the Lebanese population. The aim of the additional study
      reported here was to determine the current prevalence of hepatitis delta virus
      (HDV) infection and the range of HDV genotypes in this Lebanese population. Two
      hundred and fifty-eight HBsAg-positive patients (107 asymptomatic blood donors,
      92 with chronic hepatitis, 24 with cirrhosis, 15 with hepatocellular carcinoma,
      20 patients on haemodialysis) from ten medical centers in Lebanon were tested for
      antibody to hepatitis D virus (anti-HDV). Those testing positive were analysed
      further for HDV-RNA and for genotyping by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and restriction fragment length polymorphism (RFLP). Three
      samples (1.2%) were anti-HDV positive and out of these, only one was HDV-RNA
      positive (0.6%) and was analysed as HDV genotype I. Our results point to a low
      endemicity of HDV in the Lebanese population which is in sharp contrast to data
      reported from Lebanon 20 years ago and to the situation in neighbouring Arab and
      non-Arab countries in the Mediterranean region. HDV genotype I seems to be the
      predominant genotype in Lebanon and the Middle East.

PMID- 17176499
TI  - Capture-recapture estimation of underreporting of legionellosis cases to the
      National Legionellosis Register: Italy 2002.
AB  - The objective of this study was to evaluate the degree of underreporting to the
      Italian National Legionellosis Register (NLR). For the year 2002, all cases of
      Legionellosis notified to the NLR were compared with cases recorded in the
      hospital discharge record (HDR) database. The number of unreported cases and the
      total number of cases in the population were estimated using the capture
      recapture method with two independent data sources. Seventeen out of 21 Italian
      regions participated in the study. Overall, underreporting was estimated to be
      21.4% and was found to be significantly greater in the Centre-South (28.2%) than
      in the North (20.0%). However, even after taking into account the higher degree
      of underreporting, a significantly lower incidence of the disease is registered
      in central-southern Italy. The hypothesis, which needs to be verified, is that,
      in addition to underreporting, under-diagnosis of legionellosis is more
      widespread in this geographical area.

PMID- 17176500
TI  - An analysis of suicide and undetermined deaths in 17 predominantly Islamic
      countries contrasted with the UK.
AB  - BACKGROUND: Suicide is expressly condemned in the Qu'ran, and traditionally few
      Islamic countries have reported suicide. Undetermined deaths are classified by
      the World Health Organization (WHO) as Other Violent Deaths (OVD) in ICD-9, or
      Other External Causes (OEC) in ICD-10. It has been suggested that to avoid under
      reporting of suicides, both formal suicide verdicts and OVD should be considered
      together because OVD may contain 'hidden' suicides. METHOD: The latest WHO
      mortality data, by age and gender, were analysed and tested by chi2 tests. Levels
      of suicide and OVD in 17 Islamic countries were examined and contextually
      compared with UK rates. The regional Islamic cultural differences in Middle
      Eastern, South Asian, European Islam countries and those of the former Union of
      Socialist Soviet Republics (FUSSR) were analysed separately to test the
      hypotheses that there would be no difference between regional suicide and OVD
      rates per million (pm) and 17 Islamic countries and UK rates. RESULTS: Suicide
      rates were higher for males than females, and 'older' (65+) higher than 'younger'
      (15-34) rates in every country reviewed. The rate for Middle Eastern males was 0
      36 pm, South Asian 0-12 pm, European 53-177 pm and FUSSR 30-506 pm, with three
      countries exceeding the UK rate of 116 pm. The Western male average OVD rate was
      22 pm; the UK 55 pm rate was highest. Middle Eastern OVD was 1-420 pm, South
      Asian 0-166 pm, European 1-66 pm and FUSSR 11-361 pm. OVD rates in 10 Islamic
      countries were considerably higher than the Western average and eight had OVD
      rates considerably higher than their suicide rates. CONCLUSIONS: Islamic suicide
      rates varied widely and the high OVD rates, especially the Middle Eastern, may be
      a repository for hiding culturally unacceptable suicides.

PMID- 17176501
TI  - Development of a new measure of health-related quality of life for people with
      dementia: DEMQOL.
AB  - BACKGROUND: We identified the need to develop a scientifically rigorous measure
      of health-related quality of life (HRQL) in dementia that would be appropriate
      for use at all stages of dementia severity and would be available in both self-
      and proxy-report versions. METHOD: We used standard psychometric methods to
      eliminate items with poor psychometric properties (item-reduction field test) and
      to assess the acceptability, reliability and validity of the item-reduced
      instruments (psychometric evaluation field test). We developed and validated two
      versions of DEMQOL: a 28-item interviewer-administered questionnaire that is self
      reported by the person with dementia (DEMQOL) and a 31-item interviewer
      administered questionnaire that is proxy-reported by a caregiver (DEMQOL-Proxy).
      RESULTS: DEMQOL shows high reliability (internal consistency and test-retest) and
      moderate validity in people with mild/moderate dementia. DEMQOL-Proxy shows good
      acceptability and internal consistency and moderate evidence of validity in
      people with mild/moderate and severe dementia. Test-retest reliability and
      performance in people with severe dementia need further testing. CONCLUSIONS:
      DEMQOL and DEMQOL-Proxy show psychometric properties that are comparable with the
      best available dementia-specific measures of HRQL. We recommend that DEMQOL and
      DEMQOL-Proxy are used together. Reliability and validity need to be confirmed in
      independent samples and responsiveness needs to be evaluated.

PMID- 17176502
TI  - Genetic influences on measures of the environment: a systematic review.
AB  - BACKGROUND: Traditional models of psychiatric epidemiology often assume that the
      relationship between individuals and their environment is unidirectional, from
      environment to person. Accumulating evidence from developmental and genetic
      studies has made this perspective increasingly untenable. METHOD: Literature
      search using Medline, PsycINFO, article references and contact with experts to
      identify all papers examining the heritability of measures of environments of
      relevance to psychiatry/psychology. RESULTS: We identified 55 independent studies
      organized into seven categories: general and specific stressful life events
      (SLEs), parenting as reported by child, parenting reported by parent, family
      environment, social support, peer interactions, and marital quality. Thirty-five
      environmental measures in these categories were examined by at least two studies
      and produced weighted heritability estimates ranging from 7% to 39%, with most
      falling between 15% and 35%. The weighted heritability for all environmental
      measures in all studies was 27%. The weighted heritability for environmental
      measures by rating method was: self-report 29%, informant report 26%, and direct
      rater or videotape observation (typically examining 10 min of behavior) 14%.
      CONCLUSION: Genetic influences on measures of the environment are pervasive in
      extent and modest to moderate in impact. These findings largely reflect 'actual
      behavior' rather than 'only perceptions'. Etiologic models for psychiatric
      illness need to account for the non-trivial influences of genetic factors on
      environmental experiences.

PMID- 17176503
TI  - Slow habituation of arousal associated with psychosis proneness.
AB  - BACKGROUND: Previous studies report skin conductance (SC) abnormalities in both
      patients with schizophrenia and psychosis-prone individuals. However, no studies
      have assessed SC abnormalities in relation to specific psychotic and emotional
      symptoms. The aim of the present study was to examine the relationship between SC
      orienting response and hallucination proneness, delusional ideation, anxiety and
      self-focused attention in non-clinical individuals. METHOD: Forty-three
      participants were recruited and divided into two groups depending upon the SC
      habituation profile. Normal habituators (n=28) and slow habituators (n=15) were
      compared on measures of psychosis proneness, anxiety and self-focused attention.
      RESULTS: Slow habituators had significantly higher levels of delusional ideation
      and hallucination proneness than the normal habituators. SC habituation scores
      were particularly associated with the conviction of delusional ideas. Levels of
      anxiety or self-focused attention did not differ significantly between the
      groups. CONCLUSIONS: The study provides evidence of 'aetiological continuity'.
      Common mechanisms may contribute to psychotic experiences in non-clinical and
      clinical samples, consistent with the notion of a psychosis continuum.

PMID- 17176504
TI  - Shared genetic and environmental risk factors between undue influence of body
      shape and weight on self-evaluation and dimensions of perfectionism.
AB  - BACKGROUND: Theory and evidence strongly suggest that perfectionism may be a risk
      factor for eating disorders. The purpose of the current study was to investigate
      a model that would explain the relationship between the cognitive diagnostic
      criterion for both anorexia nervosa and bulimia nervosa, namely undue influence
      of body weight or shape on self-evaluation, and dimensions of perfectionism. The
      model of particular interest was the common cause model, which hypothesizes that
      the phenotypes are caused by the same underlying genetic and environmental risk
      factors. METHOD: Female twins (n=1002) from the Australian Twin Registry (ATR),
      aged 28 to 39 years, were interviewed using the Eating Disorder Examination
      (EDE). In addition, questions relating to the Equal Environment Assumption (EEA)
      and the Frost Multidimensional Perfectionism Scale, namely concern over mistakes
      (CM), personal standards (PS) and doubts about actions (DA), were assessed.
      RESULTS: There was no evidence of violation of the EEA for any of the four
      phenotypes. Univariate models showed all phenotypes to be influenced by both
      genetic and non-shared environmental action, where genetic estimates ranged from
      25% to 39% of the variance. Multivariate analyses suggested the best explanation
      of covariation among the phenotypes was an independent pathways, rather than a
      common pathways, model. CONCLUSIONS: Undue influence of body weight or shape on
      self-evaluation shared about 10% of its sources of genetic and environmental
      variance with perfectionism, thus suggesting that a common cause model does not
      represent the best explanation of the relationship between perfectionism and this
      cognitive diagnostic criterion for eating disorders.

PMID- 17176506
TI  - Findings of research misconduct.

PMID- 17176505
TI  - A sham-controlled trial of the efficacy and safety of twice-daily rTMS in major
      depression.
AB  - BACKGROUND: Studies of repetitive transcranial magnetic stimulation (rTMS) in
      depression have mostly involved once-daily treatment, with positive but modest
      clinical results. This study tested the efficacy and safety of twice-daily rTMS
      over 2 weeks. METHOD: Thirty-eight depressed subjects enrolled in a double-blind,
      sham-controlled trial of twice-daily rTMS (left prefrontal cortex, 10 Hz, 110%
      intensity, 1500 stimuli per session) over 2 weeks. Mood and neuropsychological
      functioning were assessed weekly by blind raters, using the Montgomery-Asberg
      Depression Rating Scale (MADRS) as the primary outcome measure, plus the Hamilton
      Rating Scale for Depression (HRSD) and self-report measures. After the blind
      period, 22 subjects continued with once-daily rTMS to receive a total of 6 weeks
      of active rTMS. RESULTS: Subjects were moderately treatment resistant. Active
      treatment resulted in significantly greater improvement than sham over the 2-week
      blind period on one outcome measure only (MADRS p<0.05). Subjects showed further
      improvement over the 6 weeks of active rTMS. Neuropsychological test scores did
      not change significantly. CONCLUSIONS: rTMS given twice daily was effective and
      safe, with no adverse neuropsychological effects.

PMID- 17176508
TI  - Disaster preparedness and emergency communications.

PMID- 17176509
TI  - Aiming high: 10 steps to a high-performance health system.

PMID- 17176510
TI  - Chest X-ray quiz. Intragastric tube in wrong place.

PMID- 17176511
TI  - The health of Europe's most marginalised populations.

PMID- 17176512
TI  - Polish drug factory closed after treatment mix up.

PMID- 17176514
TI  - Retraction notice to "MDMA- and p-chlorophenylalanine-induced reduction in 5-HT
      concentrations: effects on serotonin transporter densities" [Eur. J. Pharmacol.
      453 (2002) 239-244].

PMID- 17176513
TI  - Retraction notice to "Expression of matrix metalloproteinase-26 (MMP-26) mRNA in
      mouse uterus during the estrous cycle and early pregnancy".

PMID- 17176516
TI  - Nanobiotechnology: small talk.

PMID- 17176515
TI  - [Psychoeducation from a psychiatric-psychotherapeutic point of view].

PMID- 17176517
TI  - Public understanding of prolonged ED waiting times.

PMID- 17176519
TI  - Health tips. Controlling dandruff.

PMID- 17176518
TI  - Systolic hypertension. A specific kind of high blood pressure.

PMID- 17176520
TI  - New prescription drug available to help smokers stop.

PMID- 17176521
TI  - Urinary tract infections. Common in older adults.

PMID- 17176522
TI  - Cooking with less salt. Spice up your life.

PMID- 17176523
TI  - My granddaughter was recently visiting and she had chickenpox. I've already had
      chickenpox, but I'm concerned about getting shingles because I know the two
      diseases are related. Can I catch shingles from her?

PMID- 17176524
TI  - Identification with sport teams as a function of the search for certainty.
AB  - Based on ideas from subjective uncertainty reduction theory, we examined the
      extent to which individuals hold similar sport team preferences to their family
      and friends. We also assessed the extent to which perceived sport importance and
      personal need for structure are influential in the development of team
      identification. Australian high school students aged 15.5+/-1.0 years (mean+/-s)
      completed questionnaires containing the Personal Need for Structure Scale, the
      Relational-Interdependent Self-Construal scale, a Team Identification Scale, and
      items assessing perceptions of sport importance and team preferences. As
      expected, correlations indicated that preferences for sport teams were
      significantly related to the preferences of family and friends. Separate analyses
      of variance confirmed the remaining hypotheses. More specifically, individuals
      who perceived that sport was important identified with the team more than
      individuals who perceived sport to be less important. Also, individuals high in
      personal need for structure scored higher in cognitive/affective team
      identification than those low in this need. Individuals with differing needs for
      structure did not differ in their scores on other dimensions of team
      identification. The results support the notion that cognitive/emotional
      attachments to sport teams are influenced by perceptions of the importance of
      sport and by needs for subjective structure. It is possible that other
      psychological motives, such as the desire for self-esteem, facilitate the
      development of evaluative dimensions of team identification.

PMID- 17176525
TI  - The distance-time relationship over a century of running Olympic performances: A
      limit on the critical speed concept.
AB  - We analyse the evolution of the slope (critical speed) and the y-intercept
      (anaerobic distance capacity) of the linear distance-time relationship over a
      century of Olympic running performances. The distance-time relationship of each
      Olympic Games (1920-2004) was plotted using the performances in the 800-, 1500-
      and 5000-m track events. Values for critical speed and anaerobic distance
      capacity were determined by linear modelling. Mean performances for the 800, 1500
      and 5000 m were 104.9 +/- 1.5 s (1.4%), 217.2 +/- 2.8 s (1.3%) and 808.9 +/- 18.4
      s (2.3%), respectively. Critical speed improved during the first three-quarters
      of the twentieth century to reach a plateau in 1984. This is in accordance with
      the literature (Peronnet & Thibault, 1989) and suggests that "human aerobic
      endurance" has improved within the century (+13.4%) and tends to stabilize.
      Anaerobic distance capacity was highly variable over the century (coefficient of
      variation = 9.4%) and did not show a linear improvement over the years as has
      previously been suggested (Peronnet & Thibault, 1989). This could be due to an
      artefact in the application of the two-parameter model to only three Olympic
      performances. A limitation to the use of this linear mathematical model to fit
      physiological data may have been demonstrated.

PMID- 17176526
TI  - The role of effort in moderating the anxiety-performance relationship: Testing
      the prediction of processing efficiency theory in simulated rally driving.
AB  - We tested some of the key predictions of processing efficiency theory using a
      simulated rally driving task. Two groups of participants were classified as
      either dispositionally high or low anxious based on trait anxiety scores and
      trained on a simulated driving task. Participants then raced individually on two
      similar courses under counterbalanced experimental conditions designed to
      manipulate the level of anxiety experienced. The effort exerted on the driving
      tasks was assessed though self-report (RSME), psychophysiological measures (pupil
      dilation) and visual gaze data. Efficiency was measured in terms of efficiency of
      visual processing (search rate) and driving control (variability of wheel and
      accelerator pedal) indices. Driving performance was measured as the time taken to
      complete the course. As predicted, increased anxiety had a negative effect on
      processing efficiency as indexed by the self-report, pupillary response and
      variability of gaze data. Predicted differences due to dispositional levels of
      anxiety were also found in the driving control and effort data. Although both
      groups of drivers performed worse under the threatening condition, the
      performance of the high trait anxious individuals was affected to a greater
      extent by the anxiety manipulation than the performance of the low trait anxious
      drivers. The findings suggest that processing efficiency theory holds promise as
      a theoretical framework for examining the relationship between anxiety and
      performance in sport.

PMID- 17176527
TI  - The economics of HIV/AIDS in low-income countries: the case for prevention.

PMID- 17176528
TI  - The growth in the Social Security Disability rolls: a fiscal crisis unfolding.

PMID- 17176529
TI  - Photoselective vaporization for benign prostatic hyperplasia.
AB  - (1) In photoselective vaporization of the prostate (PVP) for benign prostatic
      hyperplasia (BPH), laser energy is used to vaporize prostatic tissue rapidly and
      bloodlessly. (2) Studies suggest that PVP performs well in the short term. (3)
      Randomized controlled trials (RCTs) and longterm follow-up are required to
      determine PVP's place in the management of BPH.

PMID- 17176531
TI  - Nuclear cardiology in the literature.

PMID- 17176530
TI  - A new gene affecting the efficiency of mating-type interconversions in
      homothallic strains of Saccharomyces cerevisiae.
AB  - Homothallic strains of Saccharomyes cerevisiae are able to switch efficiently
      from one mating genotype to another. From a single haploid spore arise both a and
      mating type cells, which then self-mate to produce a colony consisting almost
      exclusively of nonmating a/ diploid cells. We have isolated a mutant homothallic
      strain that gives rise to colonies that show bisexual mating behavior. The mating
      reaction is always asymmetric, that is, in some colonies a mating is much
      stronger than mating, while others show greater than a mating.-This mating
      phenotype arises from the presence of three cell types in a colony: some a/
      nonmating diploids and an unequal number of a and haploid cells. The predominant
      haploid type is that of the original cell that gives rise to the colony. This
      mixture of cell types arises from a very reduced efficiency of homothallic mating
      type interconversions in the mutant strain.-The mutation, designated switch (swi1
      1), behaves as a single genetic locus. The mutation is centromere linked, but not
      linked to the mating type locus or to any of the homothallism genes: HO, HMa and
      HM. The switch mutation does not affect the efficiency of self-mating, but rather
      directly affects the frequency of interconversion of mating types.

PMID- 17176532
TI  - Retraction notice to "CT features of bladder small cell carcinoma".

PMID- 17176534
TI  - Proceedings of the 7th International Congress of Wavefront Sensing and Optimized
      Refractive Corrections, January 26-29, 2006, Nassau, Bahamas.

PMID- 17176533
TI  - Characterization of a mutation in yeast causing nonrandom chromosome loss during
      mitosis.
AB  - Diploid strains of the yeast Saccharomyces cerevisiae homozygous for a recessive
      chromosome loss mutation (chl) exhibit a high degree of mitotic instability.
      Cells become monosomic for chromosome III at a frequency of approximately one
      percent of all cell divisions. Chromosome loss at this high frequency is also
      found for chromosome I, and at lesser frequencies for chromosomes VIII and XVI.
      In contrast, little or no chromosome loss is found for six other linkage groups
      tested (II, V, VI, VII, XI and XVII). The chl mutation also induces a ten-fold
      increase in both intergenic and intragenic mitotic recombination on all ten
      linkage groups tested. The chl mutation does not cause an increase in spontaneous
      mutations, nor are mutant strains sensitive to UV or irradiation. The effects of
      chl during meiosis are observed primarily in reduced spore viability. A decrease
      in chromosome III linkage relationships is also found.

PMID- 17176535
TI  - Absence of interference in association with gene conversion in Sordaria fimicola,
      and presence of interference in association with ordinary recombination.
AB  - From the analysis of large samples of gene conversion asci in the g locus of
      Sordaria fimicola, it was found that neither the conversion event itself nor
      conversion-associated recombination of flanking markers cause either chiasma or
      chromatid interference with crossing over in a neighboring interval. The presence
      of more than one kind of crossover event, one causing interference the other not,
      is considered. The existence of two kinds of gene loci, one of single-cistron
      composition and the other of multiple-cistron composition, is discussed in
      relation to reciprocal recombination within a locus.

PMID- 17176536
TI  - [The war on generic drugs].

PMID- 17176537
TI  - [Post traumatic optic neuropathy: should high doses of corticosteroid therapy be
      avoided?].

PMID- 17176538
TI  - Think again: what did Descartes really know?

PMID- 17176540
TI  - Current trends in maxillofacial imaging.

PMID- 17176541
TI  - Rampant caries and labial caries -- synonyms?

PMID- 17176539
TI  - The right to a trial: Should dying patients have access to experimental drugs?

PMID- 17176542
TI  - [Current pharmacotherapy of epilepsy in adults].
AB  - The availability of new antiepileptic drugs (AEDs) has expanded the spectrum of
      medical treatment options in epilepsy. However, the development of ten new
      compounds (vigabatrin, felbamate, gabapentin, lamotrigine, topiramate, tiagabine,
      oxcarbazepine, levetiracetam, zonisamide, and pregabalin) has not changed the
      basic principles of epilepsy treatment. The choice of an AED depends upon seizure
      type or seizure syndrome, efficacy, safety, tolerability, patient age and gender,
      concomitant medication, and comorbid conditions. In general, most of the newer
      AEDs are not necessarily more effective but usually better tolerated than the
      traditional agents mainly because of their favorable pharmacokinetic profiles and
      fewer drug interactions. Because treatment options have been widened with the
      introduction of these new compounds, drug therapy can now be tailored to the
      requirements of the individual patient. Nevertheless, significant safety and
      efficacy issues continue to exist and there is a strong need for the development
      of even better agents. This clinical review focuses on current aspects of drug
      therapy in epilepsy.

PMID- 17176543
TI  - [Psychiatric comorbidity in epilepsy].
AB  - Patients with epilepsy have a high prevalence of psychiatric comorbid disorders.
      Many comorbidities have a significant impact on the medical management and
      quality of life of these patients. The main psychiatric complications in epilepsy
      include depression, anxiety disorders, and psychosis. Depression in epilepsy is
      very common, particularly among patients with partial seizures of temporal lobe
      origin. Despite its high prevalence, depression and other psychiatric
      complications remain often unrecognized and untreated in patients with epilepsy,
      and differential diagnosis may be difficult.. Comorbidity of epilepsy may be due
      to a shared pathophysiological mechanism, however, coincidence or selection bias
      cannot always be excluded. In addition, genetic, psychosocial and iatrogenic
      factors may also contribute to the comorbidity. In this review, we discuss the
      clinical impact of main psychiatric comorbidities and demonstrate that treatment
      of epilepsy extends far beyond seizure control.

PMID- 17176544
TI  - [Crisis interventions: a psychotherapeutical challenge for psychiatric
      emergencies?].
AB  - Taking care of patients consulting the emergency psychiatric unit, raises
      nosological, legal, ethical and even logistic questions for the emergency
      departments. The need for emergency psychiatric interventions has grown
      constantly during the last twenty years and clinicians were challenged to find a
      new psychotherapeutic approach, more focused on the actual symptoms presented by
      the patients than the 'classic' psychiatric interventions. The goal of this
      article is to discuss the possibility of a psychotherapeutic approach in an
      emergency department, departing from a treatment model that has been developed at
      the psychiatric emergency of the University of Milan. In this approach, the
      psychotherapeutic treatment is divided in four different stages: preparation,
      incubation, transformation and verification. The "psychiatric crisis" becomes an
      opportunity to change for the patient, being a passage rite towards a new and
      better psychological functioning.

PMID- 17176545
TI  - [Optical magnetocardiography].

PMID- 17176546
TI  - [Amaurosis fugax of cardiac origin].
AB  - We present the case of a 49 year old woman who was admitted to the emergency
      department for dyspnoea, transient amaurosis and limbs oedema. During
      hospitalisation a full workup revealed multisystemic thrombosis and dilated
      cardiomyopathy in relation with viral myocarditis due to Coxackie B infection.
      Diagnosis and treatment will be discussed in light of the litterature.

PMID- 17176547
TI  - HPLC analysis of generic antiretroviral drugs purchased in Rwanda.
AB  - A reversed phase HPLC method using photo diode array detection for the
      simultaneous quantification of lamivudine, stavudine, nevirapine, zidovudine,
      methyl paraben and propyl paraben in solid and liquid drug formulations was
      developed and validated. The separation was achieved using a Waters Symmetry C8
      column, using a mobile phase gradient comprising 50 mM NaH2PO4 (pH 3.8) and
      acetonitrile (95:5 to 45:55, v/v) and a flow gradient (0.5 to 1.0 ml/min). The
      limits of detection and quantification were below 19 ng/ml and 55 ng/ml
      respectively. The intra- and inter-day assay precisions were within 4.4% relative
      standard deviations. The developed method was applied to 12 different generic
      antiretroviral medications, consisting of tablets, capsules and solutions,
      produced by two Indian manufacturers and purchased by the Central Agency of
      Essential Drug Procurement of Rwanda for the ESTHER project in Rwanda. The
      average content of the antiretroviral agent(s) compared to the labeled amount(s)
      was 101.4%. Methyl paraben and propyl paraben, added to solutions as
      preservatives, were within the FDA recommended limits.

PMID- 17176548
TI  - [Paratuberculosis in cattle. Reflections on the interactions with Crohn disease
      in humans. A literature review].
AB  - Based on more than 30 literature references, the author tries to explain the
      phenomena of paratuberculosis in cattle. He gives a short description of the
      origin of the infection, the disease categories, the diagnostic problems and
      eradication. Also the human infection with the Mycobacterium known as
      Mycobacterium avium supspecies paratuberculosis (MAP)--a recognized pathogen in
      animals causing some or possibly all cases of Crohn's disease will be discussed.
      The conclusion is that until now no study gives evidence that MAP may be
      transmitted to humans through foods derived from cattle with MAP infection.

PMID- 17176549
TI  - [Historical vignettes. History of vasculitis].
AB  - This article gives a summary of the history of vasculitis through early and past
      descriptions. Known, reported and depicted since time immemorial those diseases
      are quite polymorphous, depending on type and localization of the affected
      vessels. Clear classification criteria were finally laid down at the end of the
      XXth century giving a new impulse as well to the detection and the identification
      of specific biological markers as to the way to treat effectively those severe
      diseases.

PMID- 17176550
TI  - [150 years of the Central Neuropsychiatric Hospital in Luxemburg. Dr. Pierre
      Schmit: a psychiatrist in spite of himself?].
AB  - The author discusses a "case of traditional hysteria" reported by Pierre Schmit,
      the first physician (1855-1866) of the Centre Hospitalier Neuropsychiatrique of
      Ettelbruck (Luxemburg), founded in 1855. Like Louise Lateau, a celebrated Belgian
      mystic living in the second half of the XIXth century, the patient suffered from
      ecstasy and stigma. The therapies of hysteria in this time are discussed: blood
      letting, electrotherapy, clitoridectomy...

PMID- 17176552
TI  - Somatic cell nuclei in cloning: strangers traveling in a foreign land.
AB  - The recent successes in producing cloned offspring by somatic cell nuclear
      transfer are nothing short of remarkable. This process requires the somatic cell
      chromatin to substitute functionally for both the egg and the sperm genomes, and
      indeed the processing of the transferred nuclei shares aspects in common with
      processing of both parental genomes in normal fertilized embryos. Recent studies
      have yielded new information about the degree to which this substitution is
      accomplished. Overall, it has become evident that multiple aspects of genome
      processing and function are aberrant, indicating that the somatic cell chromatin
      only infrequently manages the successful transition to a competent surrogate for
      gamete genomes. This review focuses on recent results revealing these limitations
      and how they might be overcome.

PMID- 17176551
TI  - Nuclear remodeling and nuclear reprogramming for making transgenic pigs by
      nuclear transfer.
AB  - A better understanding of the cellular and molecular events that occur when a
      nucleus is transferred to the cytoplasm of an oocyte will permit the development
      of improved procedures for performing nuclear transfer and cloning. In some cases
      it appears that the gene(s) are reprogrammed, while in other cases there appears
      to be little effect on gene expression. Not only does the pattern of gene
      expression need to be reprogrammed, but other structures within the nucleus also
      need to be remodeled. While nuclear transfer works and transgenic and knockout
      animals can be created, it still is an inefficient process. However, even with
      the current low efficiencies this technique has proved very valuable for the
      production of animals that might be useful for tissue or organ transplantation to
      humans.

PMID- 17176553
TI  - Cloning cattle: the methods in the madness.
AB  - Somatic cell nuclear transfer (SCNT) is much more widely and efficiently
      practiced in cattle than in any other species, making this arguably the most
      important mammal cloned to date. While the initial objective behind cattle
      cloning was commercially driven--in particular to multiply genetically superior
      animals with desired phenotypic traits and to produce genetically modified
      animals-researchers have now started to use bovine SCNT as a tool to address
      diverse questions in developmental and cell biology. In this paper, we review
      current cattle cloning methodologies and their potential technical or biological
      pitfalls at any step of the procedure. In doing so, we focus on one
      methodological parameter, namely donor cell selection. We emphasize the impact of
      epigenetic and genetic differences between embryonic, germ, and somatic donor
      cell types on cloning efficiency. Lastly, we discuss adult phenotypes and fitness
      of cloned cattle and their offspring and illustrate some of the more imminent
      commercial cattle cloning applications.

PMID- 17176554
TI  - Centrosome inheritance after fertilization and nuclear transfer in mammals.
AB  - Centrosomes, the main microrubule organizing centers in a cell, are nonmembrane
      bound semi-conservative organelles consisting of numerous centrosome proteins
      that typically surround a pair of perpendicularly oriented cylindrical
      centrioles. Centrosome matrix is therefore oftentimes referred to as
      pericentriolar material (PCM). Through their microtubule organizing functions
      centrosomes are also crucial for transport and distribution of cell organelles
      such as mitochondria and macromolecular complexes. Centrosomes undergo cell cycle
      specific reorganizations and dynamics. Many of the centrosome-associated proteins
      are transient and cell cycle-specific while others, such as y-tubulin, are
      permanently associated with centrosome structure. During gametogenesis, the
      spermatozoon retains its proximal centriole while losing most of the PCM, whereas
      the oocyte degenerates centrioles while retaining centrosomal proteins. In most
      mammals including humans, the spermatozoon contributes the proximal centriole
      during fertilization. Biparental centrosome contributions to the zygote are
      typical for most species with some exceptions such as the mouse in which
      centrosomes are maternally inherited and centrioles are assembled de novo during
      the blastocyst stage. After nuclear transfer in reconstructed embryos, the donor
      cell centrosome complex is responsible for carrying out functions that are
      typically fulfilled by the sperm centrosome complex during normal fertilization,
      including spindle organization, cell cycle progression and development. In
      rodents, donor cell centrioles are degraded after nuclear transfer, and
      centrosomal proteins from both donor cell and recipient oocytes contribute to
      mitotic spindle assembly. However, questions remain about the faithful
      reprogramming of centrosomes in cloned mammals and its consequences for embryo
      development. The molecular dynamics of donor cell centrosomes in nuclear transfer
      eggs need further analysis. The fate and functions of centrosome components in
      nuclear transfer embryos are being investigated by using molecular imaging of
      centrosome proteins labeled with specific markers including, but not limited to,
      green fluorescent protein (GFP).

PMID- 17176555
TI  - Developmental, behavioral, and physiological phenotype of cloned mice.
AB  - Cloning from adult somatic cells has been successful in at least ten species.
      Although generating viable cloned mammals from adult cells is technically
      feasible, prenatal and perinatal mortality is high and live cloned offspring have
      had health problems. This chapter summarizes the health consequences of cloning
      in mice and discusses possible mechanisms through which these conditions may
      arise. These studies have further significance as other assisted reproductive
      techniques (ART) also involve some of the same procedures used in cloning, and
      there are some reports that offspring generated by ART display aberrant
      phenotypes as well. At the moment, the long-term consequences of mammalian
      cloning remain poorly characterized. Data available thus far suggest that we
      should use this technology with great caution until numerous questions are
      addressed and answered.

PMID- 17176556
TI  - Nucleolar remodeling in nuclear transfer embryos.
AB  - Transcription of the ribosomal RNA (rRNA) genes occurs in the nucleolus and
      results in ribosome biogenesis. The rRNA gene activation and the associated
      nucleolus formation may be used as a marker for the activation of the embryonic
      genome in mammalian embryos and, thus serve to evaluate the developmental
      potential of embryos originating from varied nuclear transfer protocols. In
      bovine in vivo developed embryos, functional ribosome-synthesizing nucleoli
      become structurally distinct toward the end of the 4th post-fertilization cell
      cycle. In embryonic cell nuclear transfer embryos, fully developed nucleoli are
      not apparent until the 5th cell cycle, whereas in somatic cell nuclear transfer
      embryos the functional nucleoli emerge already during the 3rd cell cycle.
      Intergeneric reconstructed embryos produced by the fusion of bovine
      differentiated somatic cell to a nonactivated ovine cytoplast fail to develop
      fully functional nucleoli. In bovine in vivo developed embryos, a range of
      important nucleolar proteins (e.g., topoisomerase I, upstream binding factor and
      RNA polymerase I, fibrillarin, nucleophosmin and nucleolin) become localized to
      the nucleolar anlage over several cell cycles. This relocation is completed
      toward the end of the 4th cell cycle. A substantial proportion of bovine embryos
      produced by nuclear transfer of embryonic or somatic cells to bovine ooplasts
      display aberrations in protein localization in one or more blastomers. This
      information is indicative of underlying aberrations in genomic reprogramming and
      may help to explain the abnormalities observed in a proportion of fetuses and
      offspring derive from nuclear transfer embryos.

PMID- 17176557
TI  - Somatic cell nuclear transfer (SCNT) in mammals: the cytoplast and its
      reprogramming activities.
AB  - It is now more than nine years since Dolly, the world's first somatic cell cloned
      mammal was born, and the success of somatic cell nuclear transfer (SCNT) is still
      disappointingly low. Only about 3-5% of reconstructed embryos develop to term,
      and it is also evident that even if some clones are born, they are not
      necessarily fully developed and healthy. Embryonic and neonatal abnormalities of
      cloned offspring are probably a result of incorrect or incomplete reprogramming
      of the transferred donor cell nuclei. Such an incomplete reprogramming reflects
      the extremely low efficiency of SCNT. The key role in the process of
      reprogramming has been attributed to the enucleated oocyte-cytoplast into which
      the somatic cell nucleus is transferred. In our chapter, we will discuss the
      methodological approaches used for the preparation of cytoplasts and their
      possible reprogramming activities.

PMID- 17176558
TI  - Mitochondrial DNA inheritance after SCNT.
AB  - Mitochondrial biogenesis and function is under dual genetic control and requires
      extensive interaction between biparentally inherited nuclear genes and maternally
      inherited mitochondrial genes. Standard SCNT procedures deprive an oocytes'
      mitochondrial DNA (mtDNA) of the corresponding maternal nuclear DNA and require
      it to interact with an entirely foreign nucleus that is again interacting with
      foreign somatic mitochondria. As a result, most SCNT embryos, -fetuses, and 
      offspring carry somatic cell mtDNA in addition to recipient oocyte mtDNA, a
      condition termed heteroplasmy. It is thus evident that somatic cell mtDNA can
      escape the selective mechanism that targets and eliminates intraspecific sperm
      mitochondria in the fertilized oocyte to maintain homoplasmy. However, the
      factors responsible for the large intra- and interindividual differences in
      heteroplasmy level remain elusive. Furthermore, heteroplasmy is probably
      confounded with mtDNA recombination. Considering the essential roles of
      mitochondria in cellular metabolism, cell signalling, and programmed cell death,
      future experiments will need to assess the true extent and impact of unorthodox
      mtDNA transmission on various aspects of SCNT success.

PMID- 17176559
TI  - Activation of fertilized and nuclear transfer eggs.
AB  - In all animal species, initiation of embryonic development occurs shortly after
      the joining together of the gametes from each of the sexes. The first of these
      steps, referred to as "egg activation", is a series of molecular events that
      results in the syngamy of the two haploid genomes and the beginning of cellular
      divisions for the new diploid embryo. For many years it has been known that the
      incoming sperm drives this process, as an unfertilized egg will remain dormant
      until it can no longer sustain normal metabolic processes. Until recently, it was
      also believed that the sperm was the only cell capable of creating a viable
      embryo and offspring. Recent advances in cell biology have allowed researchers to
      not only understand the molecular mechanisms of egg activation, but to exploit
      the use of pharmacological agents to bypass sperm-induced egg activation for the
      creation of animals by somatic cell nuclear transfer. This chapter will focus on
      the molecular events of egg activation in mammals as they take place during
      fertilization, and will discuss how these mechanisms are successfully bypassed in
      processes such as somatic cell nuclear transfer.

PMID- 17176560
TI  - Malaria epidemics and interventions, Kenya, Burundi, southern Sudan, and
      Ethiopia, 1999-2004.
AB  - Quantitative data on the onset and evolution of malaria epidemics are scarce. We
      review case studies from recent African Plasmodium falciparum epidemics (Kisii
      and Gucha Districts, Kenya, 1999; Kayanza Province, Burundi, 2000-2001; Aweil
      East, southern Sudan, 2003; Gutten and Damot Gale, Ethiopia, 2003-2004). We
      highlight possible epidemic risk factors and review delays in epidemic detection
      and response (up to 20 weeks), essentially due to poor case reporting and
      analysis or low use of public facilities. Epidemics lasted 15-36 weeks, and
      patients' age profiles suggested departures from classical notions of epidemic
      malaria everywhere but Burundi. Although emergency interventions were mounted to
      expand inpatient and outpatient treatment access, we believe their effects were
      lessened because of delays, insufficient evaluation of disease burden, lack of
      evidence on how to increase treatment coverage in emergencies, and use of
      ineffective drugs.

PMID- 17176561
TI  - Birds and influenza H5NI virus movement to and within North America.
AB  - Highly pathogenic avian influenza (HPAI) H5N1 expanded considerably during 2005
      and early 2006 in both avian host species and geographic distribution. Domestic
      waterfowl and migratory birds are reservoirs, but lethality of this subtype
      appeared to initially limit migrant effectiveness as introductory hosts. This
      situation may have changed, as HPAI H5N1 has recently expanded across Eurasia and
      into Europe and Africa. Birds could introduce HPAI H5N1 to the Western Hemisphere
      through migration, vagrancy, and importation by people. Vagrants and migratory
      birds are not likely interhemispheric introductory hosts; import of infected
      domestic or pet birds is more probable. If reassortment or mutation were to
      produce a virus adapted for rapid transmission among humans, birds would be
      unlikely introductory hosts because of differences in viral transmission
      mechanisms among major host groups (i.e., gastrointestinal for birds, respiratory
      for humans). Another possible result of reassortment would be a less lethal form
      of avian influenza, more readily spread by birds.

PMID- 17176562
TI  - Novel chikungunya virus variant in travelers returning from Indian Ocean islands.
AB  - Chikungunya virus (CHIKV) emerged in Indian Ocean islands in 2005 and is causing
      an ongoing outbreak that involves >260,000 patients, including travelers
      returning home from these islands. We investigated cases in 4 patients returning
      from Mayotte and Reunion Islands with CHIKV infection and a nurse infected in
      metropolitan France after direct contact with the blood of a traveler. Four
      patients had tenosynovitis and pain at wrist pressure, and 1 had life-threatening
      manifestations. Four CHIKV strains were isolated, including 1 from the patient
      with the autochthonous case. The complete genomic sequence identified a new CHIKV
      variant emerging from the East/ central African evolutionary lineage. Aedes
      albopictus, the implicated vector of CHIKV in Indian Ocean islands, has dispersed
      worldwide in recent decades. High viral loads in patients returning from Indian
      Ocean islands to countries where Ae. albopictus is prevalent may be a source of
      epidemics.

PMID- 17176563
TI  - Campylobacter jejuni multilocus sequence types in humans, northwest England, 2003
      2004.
AB  - Detailed understanding of the epidemiology of Campylobacter is increasingly
      facilitated through use of universal and reproducible techniques for accurate
      strain differentiation and subtyping. Multilocus sequence typing (MLST) enables
      discriminatory subtyping and grouping of isolate types into genetically related
      clonal complexes; it also has the advantage of ease of application and
      repeatability. Recent studies suggest that a measure of host association may be
      distinguishable with this system. We describe the first continuous population
      based survey to investigate the potential of MLST to resolve questions of
      campylobacteriosis epidemiology. We demonstrate the ability of MLST to identify
      variations in the epidemiology of campylobacteriosis between distinct populations
      and describe the distribution of key subtypes of interest.

PMID- 17176564
TI  - Active surveillance for candidemia, Australia.
AB  - Population-based surveillance for candidemia in Australia from 2001 to 2004
      identified 1,095 cases. Annual overall and hospital-specific incidences were
      1.81/100,000 and 0.21/1,000 separations (completed admissions), respectively.
      Predisposing factors included malignancy (32.1%), indwelling vascular catheters
      (72.6%), use of antimicrobial agents (77%), and surgery (37.1%). Of 919 episodes,
      81.5% were inpatient healthcare associated (IHCA), 11.6% were outpatient
      healthcare associated (OHCA), and 6.9% were community acquired (CA). Concomitant
      illnesses and risk factors were similar in IHCA and OHCA candidemia. IHCA
      candidemia was associated with sepsis at diagnosis (p<0.001), death <30 days
      after infection (p<0.001), and prolonged hospital admission (p<0.001). Non
      Candida albicans species (52.7%) caused 60.5% of cases acquired outside hospitals
      and 49.9% of IHCA candidemia (p = 0.02). The 30-day death rate was 27.7% in those
      > or =65 years of age. Adult critical care stay, sepsis syndrome, and
      corticosteroid therapy were associated with the greatest risk for death.
      Systematic epidemiologic studies that use standardized definitions for IHCA,
      OHCA, and CA candidemia are indicated.

PMID- 17176565
TI  - Active cytomegalovirus infection in patients with septic shock.
AB  - Cytomegalovirus (CMV) is a pathogen of emerging importance for patients with
      septic shock. In this prospective study, 25 immunocompetent CMV-seropositive
      patients with septic shock and an intensive care unit stay of > or =7 days were
      monitored by using quantitative pp65-antigenemia assay, shell vial culture, and
      virus isolation. Within 2 weeks, active CMV infection with low-level pp65
      antigenemia (median 3 positive/5x10(5) leukocytes) developed in 8 (32%) patients.
      Infection was controlled within a few weeks (median 26 days) without use of
      antiviral therapy. Duration of intensive care and mechanical ventilation were
      significantly prolonged in patients with active CMV infection. CMV reactivation
      was associated with concomitant herpes simplex virus reactivation (p = 0.004).
      The association between active CMV infection and increased illness could open new
      therapeutic options for patients with septic shock. Future interventional studies
      are required.

PMID- 17176566
TI  - Antimicrobial drugs in the home, United Kingdom.
AB  - A total of 6% of 6,983 households in the United Kingdom had leftover
      antimicrobial drugs, and 4% had standby antimicrobial drugs. Respondents with
      leftover drugs were more educated, more knowledgeable about antimicrobial drugs,
      younger, and female. Of respondents with leftover drugs, 44% kept them in case of
      future need, and 18% had taken these drugs without medical advice.

PMID- 17176567
TI  - Human prion disease and relative risk associated with chronic wasting disease.
AB  - The transmission of the prion disease bovine spongiform encephalopathy (BSE) to
      humans raises concern about chronic wasting disease (CWD), a prion disease of
      deer and elk. In 7 Colorado counties with high CWD prevalence, 75% of state
      hunting licenses are issued locally, which suggests that residents consume most
      regionally harvested game. We used Colorado death certificate data from 1979
      through 2001 to evaluate rates of death from the human prion disease Creutzfeldt
      Jakob disease (CJD). The relative risk (RR) of CJD for CWD-endemic county
      residents was not significantly increased (RR 0.81, 95% confidence interval [CI]
      0.40-1.63), and the rate of CJD did not increase over time (5-year RR 0.92, 95%
      CI 0.73-1.16). In Colorado, human prion disease resulting from CWD exposure is
      rare or nonexistent. However, given uncertainties about the incubation period,
      exposure, and clinical presentation, the possibility that the CWD agent might
      cause human disease cannot be eliminated.

PMID- 17176568
TI  - Human rotavirus G9 and G3 as major cause of diarrhea in hospitalized children,
      Spain.
AB  - In Spain, diarrhea remains a major cause of illness among infants and young
      children. To determine the prevalence of rotavirus genotypes and temporal and
      geographic differences in strain distribution, a structured surveillance study of
      hospitalized children <5 years of age with diarrhea was initiated in different
      regions of Spain during 2005. Rotavirus was detected alone in samples from 362
      (55.2%) samples and as a coinfection with other viruses in 41 samples (6.3%).
      Enteropathogenic bacterial agents were detected in 4.9% of samples; astrovirus
      and norovirus RNA was detected in 3.2% and 12.0% samples, respectively; and
      adenovirus antigen was detected in 1.8% samples. Including mixed infections, the
      most predominant G type was G9 (50.6%), followed by G3 (33.0%) and G1 (20.2%).
      Infection with multiple rotavirus strains was detected in >11.4% of the samples
      studied during 2005.

PMID- 17176569
TI  - Low frequency of poultry-to-human H5NI virus transmission, southern Cambodia,
      2005.
AB  - To understand transmission of avian influenza A (H5N1) virus, we conducted a
      retrospective survey of poultry deaths and a seroepidemiologic investigation in a
      Cambodian village where a 28-year-old man was infected with H5N1 virus in March
      2005. Poultry surveys were conducted within a 1-km radius of the patient's
      household. Forty-two household flocks were considered likely to have been
      infected from January through March 2005 because >60% of the flock died, case
      fatality ratio was 100%, and both young and mature birds died within 1 to 2 days.
      Two sick chickens from a property adjacent to the patient's house tested positive
      for H5N1 on reverse transcription-PCR. Villagers were asked about poultry
      exposures in the past year and tested for H5N1 antibodies. Despite frequent,
      direct contact with poultry suspected of having H5N1 virus infection, none of 351
      participants from 93 households had neutralizing antibodies to H5N1. H5N1 virus
      transmission from poultry to humans remains low in this setting.

PMID- 17176571
TI  - West Nile virus isolation from equines in Argentina, 2006.
AB  - West Nile virus (WNV) was isolated from the brains of 3 horses that died from
      encephalitis in February 2006. The horses were from different farms in central
      Argentina and had not traveled outside the country. This is the first isolation
      of WNV in South America.

PMID- 17176570
TI  - Health benefits, risks, and cost-effectiveness of influenza vaccination of
      children.
AB  - We estimated cost-effectiveness of annually vaccinating children not at high risk
      with inactivated influenza vaccine (IIV) to range from US $12,000 per quality
      adjusted life year (QALY) saved for children ages 6-23 months to $119,000 per
      QALY saved for children ages 12-17 years. For children at high risk (preexisting
      medical conditions) ages 6-35 months, vaccination with IIV was cost saving. For
      children at high risk ages 3-17 years, vaccination cost $1,000-$10,000 per QALY.
      Among children notat high risk ages 5-17 years, live, attenuated influenza
      vaccine had a similar cost-effectiveness as IIV. Risk status was more important
      than age in determining the economic effects of annual vaccination, and
      vaccination was less cost-effective as the child's age increased. Thus, routine
      vaccination of all children is likely less cost-effective than vaccination of all
      children ages 6-23 months plus all other children at high risk.

PMID- 17176572
TI  - Nematode symbiont for Photorhabdus asymbiotica.
AB  - Photorhabdus asymbiotica is an emerging bacterial pathogen that causes locally
      invasive soft tissue and disseminated bacteremic infections in the United States
      and Australia. Although the source of infection was previously unknown, we report
      that the bacterium is found in a symbiotic association with an insect-pathogenic
      soil nematode of the genus Heterorhabditis.

PMID- 17176573
TI  - Chikungunya infection in travelers.
AB  - The largest described outbreak of chikungunya virus has been occurring on the
      islands of the southwest Indian Ocean since March 2005. We describe the
      manifestations of chikungunya virus infection in travelers returning from these
      islands, with focus on skin manifestations.

PMID- 17176574
TI  - Siberian subtype tickborne encephalitis virus, Finland.
AB  - We isolated 11 Siberian subtype tickborne encephalitis virus (TBEV) strains from
      Ixodes persulcatus ticks from a TBEV-endemic focus in the Kokkola Archipelago,
      western Finland. Thus I. persulcatus and the Siberian TBEV are reported in a
      focus considerably northwest of their previously known range in eastern Europe
      and Siberia.

PMID- 17176575
TI  - Fourth human parechovirus serotype.
AB  - We identified a novel human parechovirus (HPeV) type (K251176-02) from a neonate
      with fever. Analysis of the complete genome showed K251176-02 to be a new HPeV
      genotype. Since K251176-02 could not be neutralized with antibodies against known
      HPeV serotypes 1-3, it should be classified as a fourth HPeV serotype.

PMID- 17176576
TI  - ICD-9 codes and surveillance for Clostridium difficile-associated disease.
AB  - We conducted a retrospective cohort study to compare Clostridium difficile
      associated disease rates determined by C. difficile-toxin assays and
      International Classification of Diseases, 9th Revision (ICD-9) codes. The
      correlation between toxin assay results and ICD-9 codes was good (K = 0.72,
      p<0.01). The sensitivity of the ICD-9 codes was 78% and the specificity was
      99.7%.

PMID- 17176577
TI  - Chikungunya outbreaks caused by African genotype, India.
AB  - Chikungunya fever is reported in India after 32 years. Immunoglobulin M
      antibodies and virus isolation confirmed the cause. Phylogenic analysis based on
      partial sequences of NS4 and E1 genes showed that all earlier isolates (1963
      1973) were Asian genotype, whereas the current and Yawat (2000) isolates were
      African genotype.

PMID- 17176578
TI  - Methicillin-resistant Staphylococcus aureus in Dutch soccer team.
AB  - An outbreak of community-acquired methicillin-resistant Staphylococcus aureus
      occurred among members and close contacts of a soccer team. Typing of the
      isolates showed the outbreak was caused by the well-known European ST80-IV
      strain. To our knowledge, this is the first report of an outbreak of this strain
      among members of a sports team.

PMID- 17176579
TI  - Helminth-related Eosinophilia in African immigrants, Gran Canaria.
AB  - Of 788 recent African adult immigrants to Las Palmas de Gran Canaria, 213 (27.0%)
      had eosinophilia. The most frequent causes were filariasis (29.4%),
      schistosomiasis (17.2%), and hookworm infection (16.8%). Stool microscopy and
      filarial and schistosomal serologic tests gave the highest diagnostic yield.
      Country of origin and eosinophil count were associated with specific diagnoses.

PMID- 17176580
TI  - Scrub typhus in Himalayas.
AB  - Himachal Pradesh state of India is situated in the outer Himalayan ranges. During
      the rainy season, several cases of acute febrile illness of unknown origin
      occurred. Orientia tsutsugamushi was identified as the causative agent by
      microimmunofluorescence and PCR. Two new genotypes of O. tsutsugamushi were
      identified in the region.

PMID- 17176581
TI  - H5N1 influenza viruses in Lao People's Democratic Republic.
AB  - A prospective surveillance program for influenza viruses was established in Lao
      People's Democratic Republic (PDR) in July of 2005. We report isolation of H5N1
      virus genetically distinct from H5N1 circulating in 2004, which indicates
      reintroduction of H5N1 into Lao PDR after its disappearance (i.e., no virologic
      or serologic evidence) for 2 years.

PMID- 17176582
TI  - Chimpanzee adenovirus antibodies in humans, sub-Saharan Africa.
AB  - Human sera from the United States, Thailand, and sub-Saharan Africa and
      chimpanzee sera were tested for neutralizing antibodies to 3 chimpanzee
      adenoviruses. Antibodies were more common in humans residing in sub-Saharan
      Africa than in humans living in the United States or Thailand. This finding
      suggests cross-species transmission of chimpanzee adenoviruses.

PMID- 17176583
TI  - Spatial epidemiology of Plasmodium vivax, Afghanistan.
AB  - Plasmodium vivax is endemic to many areas of Afghanistan. Geographic analysis
      helped highlight areas of malaria risk and clarified ecologic risk factors for
      transmission. Remote sensing enabled development of a risk map, thereby providing
      a valuable tool to help guide malaria control strategies.

PMID- 17176584
TI  - ICD-9 codes for identifying influenza hospitalizations in children.

PMID- 17176585
TI  - Chikungunya virus strains, Reunion Island outbreak.

PMID- 17176586
TI  - Legionnaires' disease and travel in Europe.

PMID- 17176587
TI  - Influenza A virus PB1-F2 gene.

PMID- 17176588
TI  - Enterovirus 75 and aseptic meningitis, Spain, 2005.

PMID- 17176589
TI  - Ciprofloxacin-resistant Salmonella Kentucky in travelers.

PMID- 17176590
TI  - KPC type beta-lactamase, rural Pennsylvania.

PMID- 17176591
TI  - Severe pneumonia and human bocavirus in adult.

PMID- 17176592
TI  - Leishmaniasis in ancient Egypt and Upper nubia.

PMID- 17176593
TI  - Tickborne encephalitis virus, northeastern Italy.

PMID- 17176594
TI  - Alex Langmuir and CDC.

PMID- 17176595
TI  - Public understanding of pandemic influenza, United Kingdom.

PMID- 17176596
TI  - Influenza C virus infection in children, Spain.

PMID- 17176597
TI  - Zoonotic cutaneous leishmaniasis, Afghanistan.

PMID- 17176598
TI  - [Risk factors for alcoholic psychosis in patients with eating disorders].
AB  - The aim of the study was to reveal risk factors for development of alcoholic
      psychosis in patients with eating disorders. Ten inpatients with anorexia nervosa
      and bulimia nervosa abusing alcohol for 1-4 years have been examined. Delirium
      tremens was diagnosed in 5 patients in the first few days of staying in the
      hospital, other 5 patients were included in the control group. Factors
      precipitating delirium tremens were low body mass index, water-electrolytic
      imbalance, severe dehydration caused by vomiting and hypoglycemia. A careful
      choice of doses of psychotropic drugs taking into account concomitant somatic
      endocrine disturbances, the degree of electrolytic imbalance and thorough
      alcoholic anamnesis is important at the earlier stage of treatment.

PMID- 17176599
TI  - [A comparative study of efficacy and tolerability of antidepressants from
      different classes in mild and moderate depression].
AB  - An effect of most known antidepressants from three classes of modern
      antidepressive drugs with different mechanisms of action--amitriptyline
      (threecyclic antidepressant), paroxetine (SSRI) and tianeptine (SSRS)--have been
      compared by the indices of efficacy and tolerability in patients with mild and
      moderate depression during 6 weeks. Though an antidepressive effect of
      amitriptyline and paroxetine was higher than that of tianeptine, a trend to its
      gradual leveling was detected in all groups at the end of the therapy. The
      results of subjective assessment of the drugs by patients revealed similarity
      between the action of paroxetine and tianeptine by tolerability as well as their
      common superiority over amitriptyline by efficacy. The simultaneous assessment of
      efficacy and tolerability of the drugs in therapy of mild and moderate depression
      gave preference to the most modern classes of antidepressants.

PMID- 17176600
TI  - [Cognitive dysfunction in elderly patients: diagnosis and treatment].
AB  - Current clinical picture, diagnosis and treatment of cognitive disturbances in
      elderly patients are reviewed with a main focus on moderate cognitive impairment
      (MCI). The results of correction of such disturbances by pronoran according to
      the "Prometei" program are considered. One hundred and thirty-two physicians from
      33 cities who treated 3210 patients took part in the study. Pronoran was
      administered to 574 patients aged over 60 years. Their health was assessed using
      the MMSE scale and clock-drawing test. Pronoran was used in the dosage of 50 mg
      daily during 12 weeks in monotherapy and in combination with vascular and
      metabolic drugs in combined therapy. The physicians reported improvement of
      cognitive functions in 82% of cases, patients--in 78%. No differences were found
      in efficacy of mono- and combined therapy.

PMID- 17176601
TI  - [An additional short-term use of benzodiazepine anxiolytics at the initial stage
      of the treatment of panic disorders].
AB  - To increase efficacy and tolerability of antidepressants in patients with panic
      attacks (PA), a benzodiazepine drug has been used at the initial stage of the
      treatment. In this study, 32 patients with PA (illness duration from 1,5 to 8
      years) received paroxetine, an antidepressant, in dosage 20 mg daily during 12
      weeks and lorazepam, a benzodiazepine drug, in dosage 2,5 mg daily during the
      first 6 weeks of the exacerbation period. A general somatic and neurological
      examination as well as a quantitative assessment of intensity of mental disorders
      (anxiety etc.) using corresponding scales have been conducted. A statistically
      significant decrease of panic attack frequency, along with anxiety and
      depression, supports the advantages of the combined therapy.

PMID- 17176602
TI  - [The use of mexidol in urgent treatment of drug addiction].
AB  - Results of the clinical study of efficacy and tolerability of mexidol
      administered in intravenous drop-by-drop introduction during 5-7 days in the
      therapy of 50 cases of complicated alcoholic delirium are presented. The patient
      condition and changes in device test data were assessed in comparison with those
      of a control group of patients receiving a basic therapy without mexidol. It is
      shown that mexidol has stopped psychosis in shortest terms thus decreasing
      secondary complications and lethality.

PMID- 17176603
TI  - [The use of katadolon in patients with spondylogenic dorsalgia].
AB  - The open non-comparative study of the efficacy of katadolon (100 mg 3 times daily
      during 2 weeks) in 90 out-patients with spondylogenic dorsalgia has been carried
      out. A good effect, i.e. the complete relief of the pain syndrome, rehabilitation
      of the ability to self-service and regress of neurological symptoms, was observed
      in 59 (65.6%) patients, a satisfactory effect, i.e. the complete relief of the
      pain syndrome with elements of restricted daily activity and symptoms of
      radiculopathy-- in 24 (26.7%) patients and a moderate effect, i.e. the presence
      of the residual pain syndrome, restricted daily activity and symptoms of
      radiculopathy,--in 7 (7.8%) patients. After the therapy, the intensity of the
      pain syndrome decreased by 4 times, from 69.7 +/- 4.3 to 17.6 +/- 0.11 according
      to the numerical scale of pain (p < 0.01), and by 2.5 times, from 2.51 +/- 0.27
      to 1.04 +/- 0.09 (p < 0.0001), according to the verbal scale of pain. At the same
      time, the ability to self-service increased by 3 times on the daily living scale
      (2.6 +/- 0.28; p < 0.0001). At the end of the treatment, the intensity of the
      pain syndrome was associated with illness duration (r = 0.538; p < 0.01) and the
      presence of the root pain syndrome (r = 0.266; p < 0.03). The drug was well
      tolerable and caused minimal side-effects.

PMID- 17176604
TI  - [The use of computer psychosemantic analysis for diagnosis of possible relapse in
      patients with schizophrenia in the period of therapeutic remission forming].
AB  - Sixty-five patients with paranoid schizophrenia were studied using a method of
      computer psychosemantic analysis, which allowed to obtain significant evidence
      that in 21 patients without clinical symptoms of acute psychosis psychosemantic
      equivalents of psychotic experience remained actual. Using clinical and
      psychometric parameters, this was further confirmed by the negative dynamics of
      mental state in 15 cases (71.4%). Sensitivity of this method was estimated as
      78.9%, reproducibility 84.6% and specificity 86.9%. These results suggest
      efficacy of the used diagnostic method for prognosis of psychosis relapse and
      assessment of therapeutic effect.

PMID- 17176605
TI  - [Platelet peripheral benzodiazepine receptors in alcoholism].
AB  - The peripheral-type benzodiazepine receptor (PBR) is an transmembrane protein,
      distinct pharmacologically, structurally and functionally from the central-type
      benzodiazepine receptor. The kinetic binding parameters of the specific PBR
      ligand, the PK11195, have been evaluated in platelets from 36 male alcoholic
      patients in relation to 19 healthy sex-matched controls. A significant increase
      of mean value of platelet PBR density was observed in patients as compared to the
      controls (4733 +/- 379 and 3358 +/- 242 fmol/mg proteins, p < 0.005). There are
      no statistically significant changes in the receptor affinity values in the group
      of patients.

PMID- 17176606
TI  - [Arterial hypertension and cerebrovascular disturbances].

PMID- 17176608
TI  - [Choice of psychotherapy: an analysis of literature].

PMID- 17176607
TI  - [The use of idebenone (noben) in neurological practice].

PMID- 17176609
TI  - Bone marrow stromal cells for repair of the spinal cord: towards clinical
      application.
AB  - Stem cells have been recognized and intensively studied for their potential use
      in restorative approaches for degenerative diseases and traumatic injuries. In
      the central nervous system (CNS), stem cell-based strategies have been proposed
      to replace lost neurons in degenerative diseases such as Parkinson's disease,
      Huntington's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease),
      or to replace lost oligodendrocytes in demyelinating diseases such as multiple
      sclerosis. Stem cells have also been implicated in repair of the adult spinal
      cord. An impact to the spinal cord results in immediate damage to tissue
      including blood vessels, causing loss of neurons, astrocytes, and
      oligodendrocytes. In time, more tissue nearby or away from the injury site is
      lost due to secondary injury. In case of relatively minor damage to the cord some
      return of function can be observed, but in most cases the neurological loss is
      permanent. This review will focus on in vitro and in vivo studies on the use of
      bone marrow stromal cells (BMSCs), a heterogeneous cell population that includes
      mesenchymal stem cells, for repair of the spinal cord in experimental injury
      models and their potential for human application. To optimally benefit from BMSCs
      for repair of the spinal cord it is imperative to develop in vitro techniques
      that will generate the desired cell type and/or a large enough number for in vivo
      transplantation approaches. We will also assess the potential and possible
      pitfalls for use of BMSCs in humans and ongoing clinical trials.

PMID- 17176610
TI  - Transplanted human neural precursor cells migrate widely but show no lesion
      specific tropism in the 6-hydroxydopamine rat model of Parkinson's disease.
AB  - Parkinson's disease (PD), while primarily associated with degeneration of
      nigrostriatal dopamine neurons, is now increasingly recognized to have more
      widespread cell loss and so the most effective cell replacement therapy should
      target all these neuronal losses. Neural precursor cells might be ideal in this
      regard as in certain circumstances they have been shown to migrate widely
      following transplantation into the CNS. The aim of this study was to investigate
      whether transplanted human expanded neural precursor cells (hENPs) could migrate
      to sites of established or evolving pathology in the adult brain using the 6
      hydroxydopamine (6-OHDA) rat model of PD. hENPs were grafted into the striatum
      prior to, at the same time as, or after the animals received a 6-OHDA lesion to
      the medial forebrain bundle. The presence of donor cells was then assessed in a
      distant site of cell loss (substantia nigra) or sites where cell death would not
      be expected (frontal cortex and globus pallidus). Donor cells were found distant
      from the site of implantation but the migration of these hENPs was not
      significantly greater in the 6-OHDA-lesioned brain and the cells did not
      specifically target the site of cell loss in the substantia nigra. The temporal
      relationship of grafting relative to the lesion, and therefore dopaminergic cell
      death, did not affect the migration of hENPs nor their differentiation. We
      conclude that while transplanted hENPs are capable of migration away from the
      site of implantation, they show no specific tropism for sites of ongoing or
      established nigral dopaminergic cell loss in this lesion model. Therefore, the
      use of such cells to replace the range of neurons lost in PD is likely to require
      a deeper understanding of the migratory cues in the damaged adult brain and some
      manipulation of these cells prior to transplantation.

PMID- 17176611
TI  - In vitro culture duration does not impact the ability of encapsulated choroid
      plexus transplants to prevent neurological deficits in an excitotoxin-lesioned
      rat model of Huntington's disease.
AB  - Delivery of neurotrophic molecules to the CNS is a potential treatment strategy
      for preventing the neuronal loss accompanying many neurological disorders.
      Choroid plexus (CP) epithelial cells secrete a cocktail of neurotrophic factors,
      and encapsulated CP transplants are neuroprotective in animal models of stroke
      and Huntington's disease (HD). Prior to clinical use, it is essential to identify
      and optimize parameters such as the length of time that transplant products such
      as encapsulated CP can be maintained. In the present study, neonatal porcine CP
      was encapsulated within alginate microcapsules and maintained in vitro for 1, 2,
      or 7 months. The encapsulated cells remained viable (>80%) at all time points and
      were transplanted unilaterally into the rat striatum. Seven days later, the same
      animals received unilateral injections of quinolinic acid (QA; 225 nmol) adjacent
      to the implant site. Separate groups of animals served as controls and received
      QA alone. After surgery, animals were periodically evaluated for weight loss and
      were tested for motor function 14 days post-QA. In controls, QA lesions produced
      a significant loss of body weight and impaired function of the contralateral
      forelimb. In contrast, implants of CP were potently neuroprotective as rats
      receiving CP transplants did not lose body weight and were not significantly
      impaired when tested for motor function. These benefits were independent of the
      length of time that the cells were held in vitro and demonstrate that the
      potential potency of alginate encapsulated CP cells can be retained for extremely
      long periods of time in vitro.

PMID- 17176612
TI  - Retinal progenitor cell xenografts to the pig retina: immunological reactions.
AB  - We evaluated the host response to murine retinal progenitor cells (RPCs)
      following transplantation to the subretinal space (SRS) of the pig. RPCs from GFP
      mice were transplanted subretinally in 18 nonimmunosuppressed normal or laser
      treated pigs. Evaluation of the SRS was performed on hematoxylin-eosin (H&E)
      stained sections. Serum samples were taken from naive and RPC-grafted pigs and
      mouse-reactive antibody responses were assessed. At 1 week, histology showed a
      few perivascular lymphocytes consistent with a mild retinal vasculitis, and
      depigmentation of the RPE with large numbers of mononuclear inflammatory cells in
      the choroid near the transplantation site. Large choroidal infiltrates were
      evident at 2-5 weeks. Serum from naive and RPC-xenografted pigs contained
      significant levels of preformed IgG and IgM antibodies against murine antigens.
      Xenogeneic RPCs transplanted to the porcine SRS induced mononuclear infiltration
      in the choroid with graft rejection occurring over 2-5 weeks. Serum analysis
      confirmed that mice and pigs are discordant species; however, a cell-mediated
      acute mechanism appears to be responsible, rather than an antibody-mediated
      rejection.

PMID- 17176613
TI  - Resolution of neurotoxicity and beta-cell toxicity in an islet transplant
      recipient following substitution of tacrolimus with MMF.
AB  - Calcineurin inhibitors such as tacrolimus have well-recognized efficacy in organ
      transplantation but side effects of nephrotoxicity, neurotoxicity, and beta-cell
      toxicity that can be particularly detrimental in islet transplantation. Neuro-
      and nephrotoxicity have been demonstrated in multiple islet transplant recipients
      despite the relatively low serum maintenance levels typically used (3-5 ng/ml).
      We describe a single patient in whom symptoms and signs of neurotoxicity
      necessitated substitution of tacrolimus with mycophenolate mofetil (MMF), which
      resulted in complete symptom resolution over the subsequent 9 months.
      Concomitantly noted were an almost immediate improvement in glycemic control and
      an improved response to stimulation testing, suggesting remission of tacrolimus
      induced beta-cell toxicity and insulin resistance. At 18 months post-"switch," 30
      months posttransplant, the patient remains insulin independent with good glycemic
      control. The goal to remove calcineurin inhibitors from regimens of islet
      transplantation is a worthy one.

PMID- 17176614
TI  - Tetracycline-regulated expression of VEGF-A in beta cells induces angiogenesis:
      improvement of engraftment following transplantation.
AB  - Early revascularization of pancreatic islet cells after transplantation is
      crucial for engraftment, and it has been suggested that vascular endothelial
      growth factor-A (VEGF-A) plays a significant role in this process. Although VEGF
      gene therapy can improve angiogenesis, uncontrolled VEGF secretion can lead to
      vascular tumor formation. Here we have explored the role of temporal VEGF
      expression, controlled by a tetracycline (TC)-regulated promoter, on
      revascularization and engraftment of genetically modified beta cells following
      transplantation. To this end, we modified the CDM3D beta cell line using a
      lentiviral vector to promote secretion of VEGF-A either in a TC-regulated (TET
      cells) or a constitutive (PGK cells) manner. VEGF secretion, angiogenesis, cell
      proliferation, and stimulated insulin secretion were assessed in vitro. VEGF
      secretion was increased in TET and PGK cells, and VEGF delivery resulted in
      angiogenesis, whereas addition of TC inhibited these processes. Insulin secretion
      by the three cell types was similar. We used a syngeneic mouse model of
      transplantation to assess the effects of this controlled VEGF expression in vivo.
      Time to normoglycemia, intraperitoneal glucose tolerance test, graft vascular
      density, and cellular mass were evaluated. Increased expression of VEGF resulted
      in significantly better revascularization and engraftment after transplantation
      when compared to control cells. In vivo, there was a significant increase in
      vascular density in grafted TET and PGK cells versus control cells. Moreover, the
      time for diabetic mice to return to normoglycemia and the stimulated plasma
      glucose clearance were also significantly accelerated in mice transplanted with
      TET and PGK cells when compared to control cells. VEGF was only needed during the
      first 2-3 weeks after transplantation; when removed, normoglycemia and graft
      vascularization were maintained. TC-treated mice grafted with TC-treated cells
      failed to restore normoglycemia. This approach allowed us to switch off VEGF
      secretion when the desired effects had been achieved. TC-regulated temporal
      expression of VEGF using a gene therapy approach presents a novel way to improve
      early revascularization and engraftment after islet cell transplantation.

PMID- 17176615
TI  - Transplantation of murine bone marrow stromal cells under the kidney capsule to
      secrete coagulation factor VIII.
AB  - Ectopic cell transplantation has been studied as an alternative to whole organ
      transplantation or as a method to produce secretable proteins for genetic
      disorders. In this study, bone marrow stromal cells isolated from C57Bl/6 mice
      were genetically modified to express either lacZ- or B-domain-deleted human
      factor VIII. In vitro modification of the isolated bone marrow stromal cells was
      initially performed by transducing increased doses of VSV-G pseudotyped
      lentiviral vectors expressing lacZ. At a MOI of 25, all of the bone marrow
      stromal cells were X-gal positive, which maintained their ability to expand and
      differentiate prior to transplantation into mice. Extremely poor engraftment was
      observed in the liver, but transplantation of the bone marrow stromal cells
      expressing lacZ under the kidney capsule resulted in long-term viable X-gal
      positive cells for at least 8 weeks (length of study). In vitro expression of
      human factor VIII was detected in a dose-dependent manner following bone marrow
      stromal cell with a factor VIII-expressing lentiviral vector. Transplantation of
      the factor VIII-expressing bone marrow stromal cells under the kidney capsule led
      to long-term therapeutic expression in the mouse plasma (1-3 ng/ml; n = 4-5
      mice/group) for 8 weeks. This study demonstrated that ectopic transplantation of
      bone marrow stromal cells under the kidney capsule can be effective as a method
      to express secretable proteins in vivo.

PMID- 17176616
TI  - Human umbilical cord blood progenitor cells are attracted to infarcted myocardium
      and significantly reduce myocardial infarction size.
AB  - We are investigating the effects of human umbilical cord blood mononuclear
      progenitor cells (HUCBC) for the treatment of acute myocardial infarction because
      human cord blood is a readily available and an abundant source of primitive cells
      that may be beneficial in myocardial repair. However, there is currently no
      scientific consensus on precisely when to inject stem/progenitor cells for the
      optimal treatment of acute myocardial infarction. We used an in vitro assay to
      determine the attraction of infarcted rat myocardium at 1, 2, 2.5, 3, 6, 12, 24,
      48, and 96 h after left anterior descending coronary artery (LAD) occlusion from
      45 rats for HUCBC in order to determine the optimal time to transplant HUCBC
      after myocardial infarction. Our assay is based on the migration of fluorescent
      DAPI-labeled HUCBC from wells in an upper chamber of a modified Boyden apparatus
      through a semiporous polycarbonate membrane into wells in a lower chamber that
      contain either normal or infarcted myocardium. DAPI-labeled HUCBC (100,000) were
      placed in each of the separate wells above the membrane that corresponded to
      normal or infarct homogenate in the lower wells. The greatest HUCBC migration to
      infarcted myocardium occurred at 2 h and 24 h after LAD occlusion in comparison
      with normal controls. A total of 76,331 +/- 3384 HUCBC migrated to infarcted
      myocardium at 2 h and 69,911 +/- 2732 at 24 h after LAD occlusion (both p <
      0.001) and significantly exceeded HUCBC migration to normal heart homogenate. The
      HUCBC migration remained greatest at 2 and 24 h after LAD occlusion when the
      number of migrated cells was adjusted for the size of each myocardial infarction.
      Injection of 106 HUCBC in saline into infarcted myocardium of non
      immunosuppressed rats within 2 h (n=10) or at 24 h (n=5) after LAD occlusion
      resulted in infarction sizes 1 month later of 6.4 +/- 0.01% and 8.4 +/- 0.02% of
      the total left ventricular muscle area, respectively, in comparison with
      infarction sizes of 24.5 +/- 0.02% (n=10) in infarcted rat hearts treated with
      only saline (p < 0.005). Acute myocardial infarction in rats treated with only
      saline increased the myocardial concentration of tumor necrosis factor-alpha (TNF
      alpha) from 6.9 +/- 0.8% to 51.3 +/- 4.6%, monocyte/macrophage chemoattractant
      protein (MCP-1) from 10.5 +/- 1.1% to 39.2 +/- 2.0%, monocyte inflammatory
      protein (MIP) from 10.6 +/- 1.6% to 23.1 +/- 1.5%, and interferon-gamma (INF
      gamma) from 8.9 +/- 0.3% to 25.0 +/- 1.7% between 2 and 12 h after coronary
      occlusion in comparison with known controls (all p < 0.001). In contrast, the
      myocardial concentrations of these cytokines in rat hearts treated with HUCBC did
      not significantly change from the controls at 2, 6, 12, and 24 h after coronary
      occlusion. The present investigations suggest that infarcted myocardium
      significantly attracts HUCBC, that HUCBC can substantially reduce myocardial
      infarction size, and that HUCBC can limit the expression of TNF-alpha, MCP-1,
      MIP, and INF-gamma in acutely infarcted myocardium.

PMID- 17176617
TI  - Use of repeating dispensers to increase the efficiency of the intramuscular
      myogenic cell injection procedure.
AB  - Intramuscular myoblast transplantation in humans and nonhuman primates requires
      precise repetitive cell injections very close to each other. Performed with
      syringes operated manually throughout large regions, this procedure takes a lot
      of time, becoming tiring and thus imprecise. We tested two repetitive dispensers
      with Hamilton syringes as cell injection devices to facilitate this procedure.
      Monkeys received intramuscular allotransplantations of beta-galactosidase-labeled
      myoblasts, using either a monosyringe or a multisyringe repeating dispenser. The
      monosyringe repeating dispenser allowed performing cell injections faster and
      easier than with a manually operated syringe. The multisyringe dispenser
      accelerated the procedure still more, but it was not ergonomic. Biopsies of the
      myoblast-injected sites 1 month later showed abundant beta-galactosidase-positive
      myofibers, with the same density and morphological pattern observed following
      myoblast transplantation with a syringe operated manually. We recommend the
      monosyringe repeating dispenser for myoblast transplantation in skeletal muscles
      and maybe in the heart.

PMID- 17176618
TI  - Cell transplantation: toward cell therapy.

PMID- 17176620
TI  - Multiple drug prescribing by general practitioners in a German region:
      Implications for drug interactions and patient safety.
AB  - OBJECTIVE: An increased number of drugs used by patients enhances the risk of
      potentially hazardous drug interactions. So far, no representative data are
      available about how common this problem is in German general practices. METHODS:
      We performed a retrospective analysis using a prescription database for a German
      region. The 50 general practitioners (out of 1,457) who wrote the most
      prescriptions during January to March 2003 were included. Data on 4,153 patients
      who were prescribed at least 10 drugs were analyzed for 92 predefined Drug
      Combinations Prone to Interact (DCPI) to a clinically relevant extent and
      possible contraindications. RESULTS: From 92 DCPIs, 71 occurred in the analyzed
      population between 1 and 275 times. The total number of DCPI cases was 1,295,
      which included 10% (n = 129) of contraindicated combinations. Among 4,153
      analyzed patients, 822 patients (19.8%) were affected by at least 1 DCPI. In 268
      patients (6.5%), multiple DCPIs occurred. The most frequently found drug pairs
      were digitalis/diuretics, digitalis/calcium channel blockers, and
      theophylline/quinolones. Among contraindicated combinations, tricyclic
      antidepressants, St. John's wort and antiarrhythmic drugs were most frequently
      involved. In about 1/3 of patients treated for chronic heart failure,
      pharmacotherapy appeared not to be guideline-adherent. CONCLUSION: Drug
      interactions, especially in polypharmacotherapy, represent a potential hazard
      which must be taken into account by the prescribing physician. Our study is the
      first to use a prescription database for the evaluation of drug prescriptions
      within a German region.

PMID- 17176619
TI  - Application of data mining to predict the dosage of vancomycin as an outcome
      variable in a teaching hospital population.
AB  - OBJECTIVE: Data mining is a process used to extract potentially valuable
      information hidden in large volumes of raw data. The aim of this study was to
      explore the possibility of using easy to implement and effective supervised
      learning techniques to predict the dosage of vancomycin. METHODS: To reach this
      goal, we considered the prediction of the dosage of vancomycin as a
      classification problem. We chose the C4.5 decision tree technique for the dosage
      prediction process and supplied it with a boosting technique to enhance its
      performance. RESULTS: The potential predictor variables were collected from 833
      patients with methicillin-resistant Staphylococcus aureus, or penicillin
      intolerance who were being treated with vancomycin and undergoing therapeutic
      drug monitoring (TDM) after attainment of steady state blood concentrations.
      Attributes tested as potential predictors included age, sex, weight, serum
      creatinine concentration, dosing interval, and variables from 1-compartment model
      kinetics such as Kd, Vd, and t(1/2). CONCLUSIONS: The results showed that the
      proposed method can utilize a variety of parameters to predict the dosage of
      vancomycin in the population used and that it performs well over a range of
      patient ages and renal function. The method may offer an alternative to existing
      methods used to support decision-making in clinical practice.

PMID- 17176622
TI  - Mass balance study of [14C] rabeprazole following oral administration in healthy
      subjects.
AB  - The study was designed to determine the excretion balance of radiolabeled
      rabeprazole in urine and feces and to examine the metabolite profile in plasma,
      urine and feces after a single oral dose of [14C] rabeprazole, preceded by once
      daily dose of rabeprazole for 7 days. Six healthy subjects were enrolled in this
      study. The study was a single-center, open-label, multiple-dose, mass-balance
      study. Each subject received a single 20 mg dose of rabeprazole tablet for 7 days
      followed by the administration of 20 mg of [14C] rabeprazole as an oral solution
      after an overnight fast on Day 8. After oral dosing of [14C] rabeprazole, the
      mean Cmax of total radioactivity was 1,080 +/- 215 ng equivalent/ml with 0.33 +/-
      0.13 hours of the mean tmax. The apparent elimination half-life of total [14C]
      radioactivity was 12.6 +/- 3.4 hours. The total [14C] recovery in urine and feces
      was 99.8 +/-0.7% by 168 hours after oral administration of [14C] rabeprazole, and
      mean cumulative [14C] radioactivity excreted in urine was 90.0 +/- 1.7% by 168
      hours and 79.8 +/- 2.5% of the radioactivity was excreted in urine within 24
      hours. Excretion via feces added to the total by 9.8%. The major radioactive
      component in the early plasma samples was rabeprazole, however the thioether and
      thioether carboxylic acid metabolites were the main radioactive components in the
      later plasma sample. These results support the previous finding that the
      substantial contribution of the non-enzymatic thioether pathway minimizes the
      effect of CYP2C19 polymorphism on the inter-individual variation ofplasma
      clearance of rabeprazole compared with other PPIs. Low levels of the sulfone
      metabolite were detected only in early plasma samples. No rabeprazole was
      detected in any urine and feces samples. The main radioactive components in urine
      were thioether carboxylic acid and mercapturic acid conjugate metabolites, and in
      the feces, the thioether carboxylic acid metabolite. The administration of [14C]
      rabeprazole was safe as evidenced by the lack of serious adverse events and the
      fact that all observed events were mild in intensity. [14C] rabeprazole was
      rapidly absorbed after oral administration and mostly excreted in urine.

PMID- 17176621
TI  - Safety profile of proton pump inhibitors according to the spontaneous reports of
      suspected adverse reactions.
AB  - OBJECTIVE: [corrected] To evaluate similarities and differences in safety among
      proton pump inhibitors (PPIs) under the usual conditions of prescription.
      METHODS: A search of spontaneous reports on adverse reactions associated with
      these drugs and registered between January 1, 2004 and December 31, 2004 was
      undertaken in the Spanish Pharmacovigilance System Database. We compared the
      frequency of reports with the consumption of PPIs, and analyzed the organ and
      system distribution for each PPI. Of the organ and system groups more commonly
      affected, diarrhea, myalgia, abnormal vision and hepatitis were selected for
      further analysis. RESULTS: Nearly 8 times more reports for omeprazole compared to
      other drugs were found but a similar difference was observed in their
      consumption. Skin and appendage disorders were more frequently reported for
      omeprazole and rabeprazole, the urinary, female reproductive and endocrine
      systems for lansoprazole, musculoskeletal for omeprazole and esomeprazole, vision
      for pantoprazole, rabeprazole and esomeprazole, gastrointestinal tract for
      omeprazole and lansoprazole and liver and biliary systems for omeprazole,
      lansoprazole and pantoprazole. Myalgia appears more often in younger patients
      than diarrhea, abnormal vision or hepatitis and shows longer periods of latency
      and recovery. The four adverse reactions analyzed were mainly reversible.
      CONCLUSION: A direct relationship was found between consumption and the number of
      reports. Some organ and system groups were affected by more than one PPI and this
      showed a specific pattern of group toxicity to these pharmacological agents. Some
      reports involved only lansoprazole and these require further analysis.

PMID- 17176623
TI  - Consumption costs of inappropriate medicines estimated from bulk purchase data:
      The example of NSAids in Guatemala.
AB  - OBJECTIVE: In contexts where access to medicines is limited or troublesome, it
      may be important to identify the cases in which there exists access to medicines,
      but where this access is "inefficient" because it results in non-healing,
      avoidable toxicity or excessive cost in conditions of similar efficacy. Despite
      obvious limitations, bulk medicines purchase data of public institutions used to
      be the only available approximation on what is consumed in some countries. The
      aim of this study was to describe the results of a qualitative analysis of bulk
      consumption data, focusing on nonsteroidal anti-inflammatory drugs (NSAIDs) as an
      example. METHOD: The list of all drugs purchased by the Health Ministry of
      Guatemala in 2004 was quantitatively and qualitatively analyzed both according to
      the number of units and value. All NSAIDs bought during that period were analyzed
      in order to find potential intervention areas which could be addressed to improve
      drug selection. RESULTS: The studied list included 693 products with a value of
      102 million US dollars. Among the top-20 purchased medicines by defined daily
      doses (DDDs) were several NSAIDs (including aceclofenac, meloxicam and
      piroxicam). Ranitidine, ciprofibrate and dimethicone were also among these top-20
      drugs. In addition, aceclofenac was among the top-20 drugs according to value.
      The cost of "second-line" NSAIDs was several times higher than the "first-line"
      diclofenac or ibuprofen. Providing equal efficacy and similar toxicity exists, a
      theoretical switch from second- to first-line NSAIDs could save up to 2,377
      million US dollars/year. CONCLUSIONS: Although it is an old and well-known
      method, the analysis of bulk consumption data continues to provide information
      that may help to identify areas of potential improvement in settings without many
      resources. In the present theoretical example, educative interventions addressed
      to rational selection of NSAIDs could save more than 2% of the annual drug
      expenditure of the country. Co-ordinated actions addressed to other drugs could
      decrease inefficient drug expenditure and improve the quality of health-care.

PMID- 17176624
TI  - Roflumilast, a once-daily oral phosphodiesterase 4 inhibitor, lacks relevant
      pharmacokinetic interactions with inhaled salbutamol when co-administered in
      healthy subjects.
AB  - OBJECTIVE: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor under
      investigation for the treatment of chronic obstructive pulmonary disease and
      asthma. In clinical practice, the drug is likely to be co-administered with
      inhaled bronchodilating beta2-adrenoceptor agonists. Therefore, this study
      investigated the pharmacokinetic characteristics of roflumilast and its
      pharmacodynamically active metabolite roflumilast N-oxide when co-administered
      with orally inhaled salbutamol in healthy subjects. METHODS: In this open,
      randomized clinical study, 12 healthy male subjects received repeated doses of
      oral roflumilast 500 microg once daily, orally inhaled salbutamol 200 microg 3
      times daily, and a combination of both drugs over 7 days according to a 3-period,
      changeover design with 14 days washout between treatments. RESULTS: Co
      administration of roflumilast and salbutamol did not markedly change roflumilast
      or roflumilast N-oxide disposition. Point estimates (90% confidence intervals) of
      area under the curve from 0-24 h (AUC 0-24) and maximum plasma concentration in
      steady state (Cmax,ss) for roflumilast with salbutamol versus roflumilast alone
      were 1.05 (0.94, 1.17) and 0.97 (0.84, 1.10); the respective point estimates (90%
      confidence intervals) for AUC 0-24 and Cmax,ss of roflumilast N-oxide were 0.98
      (0.91, 1.06) and 0.98 (0.92, 1.03). Roflumilast co-administration did not alter
      the pharmacokinetics of steady state salbutamol. The respective point estimates
      (90% confidence intervals) for AUC 0-6 and Cmax,ss of salbutamol with roflumilast
      versus salbutamol alone were 1.10 (0.99, 1.21), 1.08 (0.91, 1.28). The
      combination of both drugs was well tolerated. CONCLUSION: There were no relevant
      pharmacokinetic interactions between roflumilast and salbutamol at
      therapeutically effective doses.

PMID- 17176625
TI  - Baseline serum lipids and renal function in chronic kidney disease patients
      entering the LORD trial.
AB  - OBJECTIVE: Previous studies investigating associations between serum lipids and
      renal disease have generally not taken into account dietary intake or physical
      activity both known to influence circulating lipids. Furthermore, inclusion of
      patients on HMG-CoA reductase inhibitors may also have influenced findings due to
      the pleiotropic effect of this medication. Therefore, the aim of this study is to
      determine the relationships between serum lipids and renal function in a group of
      patients not taking lipid-lowering medication and taking into account dietary
      intake and physical activity. METHODS: Data from 100 patients enrolled in the
      Lipid Lowering and Onset of Renal Disease (LORD) trial were used in this study.
      Patients were included with serum creatinine > 120 micromol/l, and excluded if
      they were taking lipid-lowering medication. Unadjusted and adjusted relationships
      were determined between fasting serum lipid concentrations (total cholesterol,
      low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL)
      cholesterol, triglycerides and total cholesterol/HDL ratio) and measures of renal
      function (estimated glomerular filtration rate (eGFR), creatinine clearance and
      serum creatinine) and urinary protein excretion. RESULTS: Significant (p < 0.05)
      negative unadjusted relationships were found between lipids (total cholesterol,
      LDL and HDL cholesterol) and serum creatinine. In support of these findings,
      logarithmically-transformed lipids (total cholesterol, LDL and HDL cholesterol)
      were significantly associated with eGFR and creatinine clearance although the
      effects were of a smaller magnitude. Adjustment for dietary saturated fat intake
      and physical activity did not substantially change these effects. CONCLUSION:
      These data do not support the premise that lipids are associated with renal
      dysfunction in patients with normocholesterolemia.

PMID- 17176626
TI  - Beneficial effect of long-acting injectable risperidone on the neurocognitive
      deficit of a schizophrenic patient: A case report.
AB  - We report the case of a 37-year-old female patient suffering from schizophrenia,
      disorganized type. Adherence to treatment was always a major problem. During the
      last 2 years the patient was disorganized and was refusing treatment. Since the
      patient was already receiving a very high (double) dose per os, it was decided to
      administer two 50 ml ampoules of long-acting, injectable risperidone plus 5 mg of
      haloperidol per os daily. After 80 days of treatment, all positive, negative and
      even neurocognitive symptoms improved markedly. Extrapyramidal side effects did
      not appear at any stage of treatment. The most impressive neurocognitive
      improvement concerned the clock drawing test, which was in parallel with her
      improvement in both the positive and negative symptoms of the PANSS.

PMID- 17176628
TI  - Silencing of HIV-1 gene expression by two types of siRNA expression systems.
AB  - The RNA interference (RNAi) phenomenon is a recently discovered process in which
      the introduction of a double-stranded RNA (dsRNA) into cells causes the specific
      degradation of mRNA containing the same sequence. We designed mammalian
      expression vectors that direct the synthesis of small interfering RNA (siRNA)
      like transcripts and examined them for their siRNA-mediated gene interference
      targeting the env gene (NL4-3:7490-7508, E7490). We constructed siRNA expression
      vectors for two different strands (sense and antisense; tandem promoter) and for
      siRNA expressed from the short hairpin RNA (shRNA). The inhibition efficacy on
      HIV-1 replication differed between these two vectors. Notably, the shRNA vector
      pU6-env-shRNA inhibited p24 production more effectively than the tandem promoter
      expression vector pU6-env-siRNA. Furthermore, we examined the ability of
      lentiviral vectors expressing shRNA to suppress HIV-1 expression in HIV-1
      infected SupT1 cells. The env-shRNA (E 7490) almost completely suppressed HIV-1
      expression in infected cells for up to 15 days.

PMID- 17176627
TI  - Bioequivalence study of two fluoxetine capsule formulations in healthy Middle
      Eastern volunteers.
AB  - OBJECTIVE: To assess the bioequivalence of two fluoxetine hydrochloride capsule
      (20 mg) formulations (Fluoxicare capsule from Pharmacare Ltd., Chemicals and
      Cosmetics, Ramallah, Palestine, as test formulation, and Prozac from Eli Lilly
      Ltd., Basingstoke, UK, as reference formulation). DESIGN AND METHODS: The study
      was conducted open with a randomized 2-period crossover design and a 6-week
      washout period. Participants were 24 healthy male volunteers aged 18-28 years,
      divided into 2 groups of 12 subjects. One group was given the originator drug
      (reference formulation), and the other was given the test formulation. Blood
      samples were obtained at baseline and at 14 time points during the interval 0-96
      hours after drug administration. The concentrations of the samples were assayed
      spectrophotometrically at 220 nm using a Shimadzu 160 A UV-visible spectrometer.
      We calculated the plasma concentration-time curve (AUC), maximum plasma
      concentration (Cmax), and time of maximum plasma concentration (tmax) for each
      subject. Logarithmic transformation of the AUC and Cmax was used for the
      statistical analyses and to assess the bioavailability of the two formulations,
      using analyses of variance (ANOVA) and Satherwait t-tests for unequal variances.
      The ANOVA performed of tmax in Cmax, and in AUC provided the appropriate intra
      subject variance estimates to evaluate the 90% confidence intervals for the
      differences between study variables after administration of the test and
      reference formulations. Statistical analyses were conducted on AUC 0-4 as the
      extrapolated part of the AUC, a truncated area approach was adapted. RESULTS: The
      mean pharmacokinetic parameters for both of the drugs under study were as
      follows: Cmax = 61.24 (+/- 12.96) ng/ml for the test formulation, and for the
      reference formulation Cmax = 61.39 (+/- 14.1) ng/ml, the effects were
      statistically equivalent. The tmax for the test formulation was 8.25 (+/- 1.7)
      and 7.33 (+/- 0.96) for the reference formulation. The area under the curve to
      infinity (AUC 0-infinity (ng, day/ml)) for the test formulation and for the
      reference formulation were 293.02 (+/- 52.69) and 296.15 (+/- 61.69),
      respectively. CONCLUSIONS: The two formulations had equivalent pharmacokinetic
      parameters, were well-tolerated, and their relative bioavailability was 98.94%.

PMID- 17176629
TI  - Rimantadine and oseltamivir demonstrate synergistic combination effect in an
      experimental infection with type A (H3N2) influenza virus in mice.
AB  - We studied the combination effect of rimantadine hydrochloride and oseltamivir
      phosphate on mice infected with influenza A/Aichi/2/68 (H3N2) virus. Compounds
      were simultaneously administered in a 5-day-treatment course, starting 4 h before
      intranasal infection with 10 or 20 viral 50% mouse lethal doses. Initially, we
      tested combinations of oseltamivir (0.05, 0.1 and 0.2 mg/kg/day) and rimantadine
      (2.5, 5.0 and 7.5 mg/kg/day). Significant differences were recorded between
      combination-treated groups, and groups with separately applied compounds and the
      placebo group, such as: protection index of oseltamivir with 5.0 or 7.5 mg/kg
      rimantadine varied between 34-41% and 43-87%, respectively, whereas the
      individual effects of oseltamivir, 5 mg/kg of rimantadine and 7.5 mg/kg of
      rimantadine were 0-10%, 0% and 18.7-29.6%, respectively; mean survival time in
      combination-treated groups was lengthened by 3.1-6.9 days, in oseltamivir groups
      by 0-1.9 days, and in rimantadine groups by 0.8-1.3 days at 5 mg/kg and 2.6-3.2
      days at 7.5 mg/kg. The three-dimensional method of Prichard and Shipman
      characterized the combination effect as synergistic. Further, we studied the
      activity of 0.05 mg/kg/day of oseltamivir combined with 5 mg/kg of rimantadine.
      Lung virus titre in Madin Darby canine kidney cells, lung index and consolidation
      score proved the high effectiveness of the combination. When compared with the
      placebo group, a 2.8 log10 lower titre of 50% cell culture infectious dose
      (CCID50) was recorded in the combination-treated group at 48-60 h post-infection
      (the peak of lung virus growth). This is in contrast to the 0.1-1.0 log10 and 1.1
      1.4 log10 reduction in CCID50 titre observed in the oseltamivir and rimantadine
      groups, respectively. These data emphasize the high anti-influenza A potential of
      the combination.

PMID- 17176630
TI  - alpha-Glucosidase inhibitors have a prolonged antiviral effect against hepatitis
      B virus through the sustained inhibition of the large and middle envelope
      glycoproteins.
AB  - Previous work has shown that the secretion of enveloped hepatitis B virus (HBV)
      DNA and the HBV middle envelope protein (MHBs) are sensitive to glucosidase
      inhibition. Here, it is shown that HBV DNA secretion remains depressed after the
      removal of the glucosidase inhibitor and long after glucosidase function returns
      to normal. For example, glyco-processing and the secretion of alpha-1 anti
      trypsin returned to normal within 3 h of the removal of the glucosidase
      inhibitor. In contrast, the secretion of HBV did not return to normal for more
      than 7 days after the removal of the inhibitor. Consistent with the inhibition of
      HBV virion secretion, the levels of HBV L and HBV M proteins were also reduced by
      treatment with the glucosidase inhibitor and remained reduced for 7 days after
      compound withdrawal. The implications of the prolonged antiviral effect against
      HBV and the use of glucosidase inhibitors as antiviral agents are discussed.

PMID- 17176631
TI  - Anti-influenza virus activities of 4-[(1,2-dihydro-2-oxo-3H-indol-3
      ylidene)amino]-N-(4,6-dimethyl-2-pyrimidin-2-yl)benzenesulphonamide and its
      derivatives.
AB  - 4-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)amino]-N-(4,6-dimethyl-2-pyrimidinyl)
      benzenesulphonamide (SPIII-5H) and related compounds were tested for antiviral
      activity against influenza A (H1N1, H3N2, and H5N1) and B viruses in Madin Darby
      canine kidney (MDCK) cell culture. Among the compounds tested, SPIII-5H and four
      derivatives (5-chloro [SPill-5Cl], 5-bromo [SPIII-5Br], 5-methyl [SPIII-5Me] and
      N-acetyl [SPIII-NA]) showed similar antiviral potencies, with only the 5-fluoro
      (SPIII-5F) derivative being ineffective. Fifty percent effective concentration
      (EC50) values were determined in cytopathic effect (CPE) inhibition assays
      quantified by neutral red dye uptake. By this method, the active compounds were
      inhibitory to the H1N1 strain of influenza A at 2.7-5.2 microg/ml, to the H3N2
      strain of influenza A at 13.8-26.0 microg/ml, to the H5N1 strain of influenza A
      at 3.1-6.3 microg/ml and to influenza B at 7.7-11.5 microg/ml. Confirmatory virus
      yield reduction studies against influenza A (H1N1) virus demonstrated antiviral
      activity (90% inhibition) at concentrations of 2-10 microg/ml. No cytotoxic
      effects were evident in actively growing uninfected cells or stationary
      monolayers at 100 microg/ml. Potencies of the compounds were similar to those of
      ribavirin, but much less than those of oseltamivir carboxylate against the
      various viruses. Time-of-addition studies indicated the compounds inhibited an
      early step in the virus replication cycle, probably virus adsorption/penetration,
      and no virucidal activity was evident. The basic molecule is amenable to diverse
      chemical modifications, which may improve water solubility and antiviral potency.

PMID- 17176632
TI  - Evaluation of immunomodulators, interferons and known in vitro SARS-coV
      inhibitors for inhibition of SARS-coV replication in BALB/c mice.
AB  - Compounds approved for therapeutic use and in vitro inhibitors of severe acute
      respiratory syndrome coronavirus (SARS-CoV) were evaluated for inhibition in the
      mouse SARS-CoV replication model. A hybrid interferon, interferon alpha (IFN
      alpha) B/D, and a mismatched double-stranded (ds) RNA interferon (IFN) inducer,
      Ampligen (poly I:poly C124), were the only compounds that potently inhibited
      virus titres in the lungs of infected mice as assessed by CPE titration assays.
      When mice were dosed intraperitoneally (i.p.) with IFN-alpha B/D once daily for 3
      days beginning 4 h after virus exposure, SARS-CoV replication in the lungs of
      infected mice was reduced by 1 log10 at 10,000 and 32,000 IU; at the highest dose
      of 100,000 IU, virus lung titres were below detectable limits. Ampligen used i.p.
      at 10 mg/kg 4 h prior to virus exposure also reduced virus lung titres to below
      detectable limits. Nelfinavir, beta-D-N4-hydroxycytidine, calpain inhibitor VI, 3
      deazaneplanocin A and Alferon (human leukocyte IFN-alpha-n3) did not
      significantly reduce lung virus titres in mice. Anti-inflammatory agents,
      chloroquine, amodiaquin and pentoxifylline, were also inactive in vivo,
      suggesting that although they may be useful in ameliorating the hyperinflammatory
      response induced by the virus infection, they will not significantly reduce the
      replication of the virus, the inducer of inflammatory response. Thus, anti
      inflammatory agents may only be useful in treating virus lung infections if used
      in combination with agents that inhibit virus replication. In summary, the data
      suggest that induction of IFN by mismatched dsRNA or actual treatment with
      exogenous IFN-alpha can inhibit SARS-CoV replication in the lungs of mice.

PMID- 17176633
TI  - Antiviral activity of nucleoside analogues against SARS-coronavirus (SARS-coV).
AB  - The recent outbreak of severe acute respiratory syndrome (SARS), which is an
      acute respiratory illness, is caused by newly discovered SARS coronavirus (SARS
      CoV). Herein we describe the antiviral activity of several classes of nucleoside
      analogues evaluated against SARS-CoV in Vero 76 cells, some of which exhibited
      moderate activity.

PMID- 17176634
TI  - Resveratrol can only partially attenuate ethanol-induced oxidative stress in
      embryonic chick brains.
AB  - Ethanol (EtOH) exposure promotes increased levels of reactive oxygen species that
      degrade unsaturated long-chain membrane fatty acids within embryonic chick brains
      and is associated with apoptosis and reduced embryo viability. In vitro studies
      have demonstrated that resveratrol, a known antioxidant, attenuated EtOH-induced
      damage. In order to test whether or not resveratrol can attenuate EtOH-induced
      embryonic damage, fertile chicken eggs were injected daily with EtOH (6.05
      mmol/kg egg) and various concentrations of trans-resveratrol (0-29.5 mmol/kg egg)
      during the first three days of embryonic development. At 11 days of embryonic
      development, viable embryos were collected, brains isolated, and brain membrane
      fatty acid composition analyzed. Embryonic EtOH exposure promoted fewer viable
      embryos at 11 days of development as compared to controls. Embryonic EtOH
      exposure also promoted reduced levels of unsaturated long-chain membrane fatty
      acids, increased levels of saturated short-chain membrane fatty acids, and
      elevated brain lipid hydroperoxides (LPO) levels. Embryonic exposure to moderate
      (2.95 nmol/kg egg) and high (29.5 nmol/kg egg) levels of trans-resveratrol
      attenuated EtOH-induced changes in brain membrane fatty acid composition but
      failed to attenuate EtOH-induced increases in brain LPO levels and increased
      brain Casp-3 activities.

PMID- 17176635
TI  - Chronic sucrose intake reduces the antagonist effect of beta-funaltrexamine on
      morphine-induced antinociception in female but not in male rats.
AB  - Chronic ingestion of a sweet-tasting sucrose solution enhances the pain relieving
      actions of opioid agonists. These results, taken in conjunction with research
      demonstrating that sucrose stimulates the production and release of endogenous
      opioid peptides, have led to the hypothesis that the effects of palatable foods
      and fluids on pain sensitivity are mediated by the endogenous opioid system. To
      assess this hypothesis, two studies determined if chronic sucrose intake would
      block the antagonist effects of the micro-selective opioid antagonist beta
      funaltrexamine (beta-FNA) on morphine-induced antinociception. Female and male
      Long-Evans rats were maintained on chow and water, or chow, water and a 32%
      sucrose solution. In Experiment 1, after four weeks on the diets, female rats
      received 0 or 10 mg/kg (subcutaneously (s.c.)) beta-FNA, while in Experiment 2,
      male and female rats received 0, 5 or 20 mg/kg beta-FNA. Six days later, rats
      were tested for morphine-induced antinociception using the hot-water tail
      withdrawal test. Morphine, administered using a cumulative dose regime (1.0, 3.0,
      5.6, 10.0 and 31.0 mg/kg s.c.), led to dose-dependent increases in tail
      withdrawal latencies in male and female rats. Males were more sensitive to the
      pain relieving properties of morphine than females. Sucrose intake increased,
      while beta-FNA decreased the analgesic actions of morphine in males and females.
      beta-FNA was less effective in blocking the antinociceptive actions of morphine
      in sucrose-fed female rats than in females fed only chow. In contrast, diet had
      minimal effects on responses to beta-FNA in male rats.

PMID- 17176636
TI  - Activity of autonomic nervous system is related to body weight in pre-menopausal,
      but not in post-menopausal women.
AB  - This study analyzed vegetative modulation, expressed as heart rate variability
      (HRV) power spectral analysis, in lean and obese women at pre-menopausal or post
      menopausal age to reveal possible differences in menopause-related autonomic
      activity in lean and obese subjects. Sedentary women (n = 40) were divided in
      four groups: pre-menopausal lean and obese women, post-menopausal lean and obese
      subjects. The HRV-power spectrum was evaluated on a 5-min long ECG recording. The
      absolute values of the spectrum were summed in the following frequencies: a low
      frequency (0.04-0.15 Hz; LF) and high-frequency (0.15-0.40; HF) range. LF and HF
      were values used to estimate the sympathetic and parasympathetic activity. LF and
      HF values of pre-menopausal obese women are lower than values of lean women. The
      menopause induced a same decrease in LF and HF values in lean and obese subjects,
      so that no difference was found in post-menopausal groups. This experiment
      indicates that modifications of autonomic modulation can be included among
      factors related to obesity in pre-menopausal, but not post-menopausal women.

PMID- 17176637
TI  - Molecular characterization of pig ST8Sia IV--a critical gene for the formation of
      neural cell adhesion molecule and its response to sialic acid supplement in
      piglets.
AB  - ST8Sia IV (polysialyltransferase IV gene) encodes a key enzyme that is required
      for polysialic acid synthesis. Polysialic acid is a component of the neural cell
      adhesion molecule and is necessary for synaptic plasticity of neural cells. We
      characterized 5.3 kb of pig ST8Sia IV cDNA and determined its expression profile
      in different organs. In hippocampus, ST8Sia IV mRNA levels were increased
      approximately 4.5-fold in piglets with sialic acid as a milk supplement, which
      suggested that exogenous sialic acid is a conditionally essential nutrient for
      early brain development. Extensive analyses were also performed among its
      orthologs from human, mouse, rat, chicken, frog and zebrafish. Our results
      supported that the piglet is a better animal model than other nonprimate species
      in the studies of ST8Sia IV related metabolism and nutrition in human infants.
      This pig cDNA provides a basis for uncovering the roles of ST8Sia IV during
      piglet development and maturation.

PMID- 17176638
TI  - Manipulation of rat litter size during suckling influences cortical spreading
      depression after weaning and at adulthood.
AB  - Nutritional conditions early in life constitute one environmental factor that can
      influence brain electrophysiological features. Cortical spreading depression (SD)
      is a brain electrophysiological phenomenon that can be altered by the early
      nutritional status of organism. SD-velocity changes were presently studied in
      young (30-40 days old) and adult (90-120 days) rats suckled in litters formed by
      3, 6, or 12 pups (called respectively small (S), medium (M) and large (L)
      litters). Body weights and SD propagation velocities in the 3 groups varied,
      respectively in an inverse and direct way, in relation to the litter sizes. The
      present investigation provides the first systematic description of the
      effectiveness of favorable and unfavorable lactation conditions (respectively
      suckling in S and L litters) in altering cortical SD-propagation. The results
      confirm previous evidence in favor of permanent or at least long-lasting SD
      changes associated to the prevailing nutritional status during the period of fast
      brain development.

PMID- 17176639
TI  - The effect of the interaction between glucose tolerance and breakfasts varying in
      carbohydrate and fibre on mood and cognition.
AB  - As a glucose containing drink has been reported to improve memory, and missing
      breakfast has been reported to adversely influence memory late in the morning,
      meals designed to differ in their ability to release glucose into the blood
      stream were contrasted. Using a factorial design, breakfasts containing 15, 30 or
      50 g of carbohydrate and 1.5, 6 or 13 g of fibre were compared. The glucose
      tolerance of participants proved to be an important factor. Those with better
      tolerance reported better mood. Those eating breakfasts containing greater
      amounts of carbohydrate reported feeling tired rather than energetic. The amount
      of carbohydrate did not negatively affect memory in those with better glucose
      tolerance, however, the consumption of more carbohydrate resulted in more
      forgetting in those with poorer glucose tolerance. The effect with reactions
      times differed from memory in that a greater intake of carbohydrate resulted in
      faster responses later in the morning.

PMID- 17176640
TI  - A nonpungent component of steamed ginger--[10]-shogaol--increases adrenaline
      secretion via the activation of TRPV1.
AB  - We investigated the components of ginger that are involved in increasing body
      temperature. Gingerols ([6,8,10]-gingerols) and shogaols ([6,8,10]-shogaols)
      having different alkyl carbon chain lengths were targeted. All the gingerols and
      shogaols increased intracellular calcium concentration in rat transient receptor
      potential vanilloid subtype 1 (TRPV1)-expressing HEK293 cells via TRPV1. In this
      regard, the shogaols were more potent than the gingerols. Aversive responses were
      induced by [6]-, [10]-gingerol, and [6]-shogaol (5 mmol/l) in rats when these
      compounds were applied to the eye; however, no response was observed in response
      to [10]-shogaol (5 and 10 mmol/l). [10]-Shogaol induced nociceptive responses via
      TRPV1 in rats following its subcutaneous injection into the hindpaw; the pungent
      compound capsaicin (CAP) and [6]-shogaol were observed to have similar effects.
      Moreover, adrenal catecholamine secretion, which influences energy consumption,
      was promoted in rats in response to [6]- and [10]-gingerols and [6]- and [10]
      shogaols (1.6 micromol/kg, i.v.). [10]-Shogaol-induced adrenaline secretion was
      inhibited by administration of capsazepine, a TRPV1 antagonist. In conclusion,
      gingerols and shogaols activated TRPV1 and increased adrenaline secretion.
      Interestingly, [10]-shogaol is the only nonpungent compound among the gingerols
      and shogaols, suggesting its usefulness as a functional ingredient in food.

PMID- 17176641
TI  - Cognitive performance is associated with macronutrient intake in healthy young
      and middle-aged adults.
AB  - PRIMARY OBJECTIVE: The objective was to examine whether dietary intakes of
      macronutrients are associated with neuropsychological performance. RESEARCH
      DESIGN AND METHOD: Study participants were 3960 adults aged 20-59 years, who
      completed three neuropsychological tests and a 24-hour dietary recall as a part
      of the Third National Health and Nutrition Examination Survey, 1988-1994. Poor
      performance was defined as the test score below gender-specific 15th percentile.
      MAIN OUTCOMES AND RESULTS: While holding the energy percentages from different
      macronutrients, additional 100 kcal intake of energy was associated with a
      reduced odds of poor performance on serial digital learning test (OR = 0.98, 95%
      CI = 0.96, 0.99) and symbol digital substitution test (OR = 0.97, 95% CI = 0.96,
      0.99). Compared with equivalent energy from carbohydrates, each 5% of energy from
      poly-unsaturated fatty acids (PUFA) or total fat was associated with a reduced OR
      of poor performance on simple reaction time test (PUFA: OR = 0.77, 95% CI = 0.63
      0.95 and total fat: OR = 0.93, 95% CI = 0.87, 0.99). Poor global cognition was
      associated with an additional intake of 100 mg cholesterol (OR = 1.14, 95% CI =
      1.05, 1.23). These associations were more salient in men. CONCLUSION: Habitual
      intake of macronutrients is weakly but significantly associated with cognitive
      functioning. These relationships are more evident in men.

PMID- 17176642
TI  - [Between promotion and prevention].

PMID- 17176643
TI  - ["Making larger boards": health promotion by complex social interventions].

PMID- 17176644
TI  - Beyond sport and physical activity: The concept of movement in health promotion.

PMID- 17176645
TI  - Implementation of the Bangkok Charter on Health Promotion in a Globalized World:
      Experience and challenges of selected high income countries in Europe.

PMID- 17176646
TI  - Tackling health inequalities--two European projects will identify effective
      strategies from 2004 to 2007.

PMID- 17176648
TI  - Transtheoretical model-based exercise counselling for older adults in
      Switzerland: Quantitative results over a 1-year period.
AB  - OBJECTIVES: To develop and test a counselling programme based on the
      Transtheoretical Model of behavioural change, for promoting exercise in people
      over the age of 65. METHOD: The sample (n = 448) consisted of women and men aged
      between 65 and 92, recruited from Swiss GPs' practices between 2000 and 2004.
      After a baseline measurement (T1) and an initial counselling session, they
      received two counselling sessions, followed by a 12-month follow-up (T2). Changes
      in exercise behaviour were recorded by means of stage classification and the time
      spent on everyday moderate-intensity activities that increase the breathing rate.
      RESULTS: At T1 there was a tendency for women to be less physically active than
      men. T1 to T2 the proportion of inactive people fell from 12.2% to 4.2%, and the
      proportion of people sufficiently active rose from 19.0 % to 31.3 %. The changes
      in stage were significant in both men and women. At T2 more than half of the
      participants in the study spent more time exercising. CONCLUSIONS: The results
      indicate that, with counselling, the exercise behaviour of the elderly can be
      positively influenced over a 1-year period.

PMID- 17176647
TI  - Process evaluation of a Dutch community intervention to improve health related
      behaviour in deprived neighbourhoods.
AB  - OBJECTIVES: To assess whether a community intervention on health related
      behaviour in deprived neighbourhoods was delivered as planned and the extent of
      exposure to the intervention programme. METHODS: Data were gathered throughout
      the intervention period using minutes of meetings, registration forms and a
      postal questionnaire among residents in intervention and comparison
      neighbourhoods. RESULTS: Overall, the intervention was delivered according to the
      key principles of a "community approach", although community participation could
      have been improved. Neighbourhood coalitions organized more than 50 health
      related activities in the neighbourhoods over a two-year period. Most activities
      were directed at attracting attention, providing information, and increasing
      awareness and knowledge, and at changing behaviours. Programme awareness and
      programme participation were 24% respectively 3% among residents in the
      intervention neighbourhoods. CONCLUSIONS: The process evaluation indicated that
      it was feasible to implement a community intervention according to the key
      principles of the "community approach" in deprived neighbourhoods. However, it is
      unlikely that the total package of intervention activities had enough strength
      and sufficient exposure to attain community-wide health behaviour change.

PMID- 17176649
TI  - Health-enhancing physical activity and the preventionof chronic diseases--an
      epidemiological review.
AB  - OBJECTIVES: To review the epidemiological evidence on the health-enhancing
      physical activity recommendation of the Centers for Disease Control and
      Prevention (CDC) and the American College for Sports Medicine (ACSM). METHODS:
      Review of papers written in English and German, issued after the release of the
      CDC/ACSM recommendation (i.e. after 1995), restricted to adults and to their
      physical health. Due to the large body of published data, no systematic review
      was performed. Instead, a representative cross-section of the published studies
      is presented. RESULTS: The international epidemiological evidence supports the
      CDC/ACSM recommendation as a reasonable public health message. CONCLUSIONS:
      According to this recommendation, the daily accumulation of 30 minutes of
      physical activity of moderate intensity - independent of the context of physical
      activity (e.g. transport, leisure) - provides substantial benefits across a broad
      range of health outcomes for sedentary men and women. Nevertheless some
      controversial issues need further address.

PMID- 17176650
TI  - Is water fluoridation effective in reducing inequalities in dental caries
      distribution in developing countries? Recent findings from Brazil.
AB  - OBJECTIVES: To assess socioeconomic differences between towns with and without
      water fluoridation, and to compare dental caries levels among socioeconomic
      strata in fluoridated and non-fluoridated areas. METHODS: A countrywide survey of
      oral health performed in 2002-03 and comprising 34,550 children aged 12 years
      provided information about dental caries levels in 249 Brazilian towns.
      Socioeconomic indices, the coverage and the fluoride status of the water supply
      network of participating towns were also appraised. Multivariate regression
      models fitted the adjustment of dental caries levels and covariates to
      socioeconomic status and water supply. Inequalities in dental outcomes were
      compared in towns with and without fluoridated tap water. RESULTS: Better-off
      towns tended to present a higher coverage by the water supply network, and were
      more inclined to add fluoride. Fluoridated tap water was associated with an
      overall improved profile of caries, concurrent with an expressively larger
      inequality in the distribution of dental disease. CONCLUSION: Suppressing
      inequalities in the distribution of dental caries requires an expanded access to
      fluoridated tap water; a strategy that can be effective to foster further
      reductions in caries indices.

PMID- 17176651
TI  - Television viewing and food consumption in Flemish adolescents in Belgium.
AB  - OBJECTIVES: To examine associations of television viewing with overall food
      consumption METHODS: A computerised 24-hour dietary recall and a questionnaire
      were completed by 1031 adolescents (+/- 12-14 years of age). RESULTS: Those who
      generally watched more television were more likely to consume frequently
      advertised items such as soft drinks and snacks. Not all frequently advertised
      food items (e.g. cereals) were associated with television viewing. An inverse
      association was found with fruit, water and milk. A negative association was
      found with brown bread; a positive association was found with white bread. The
      results indicate that high television viewing and a less nutrient dense food
      pattern are part of a lifestyle influenced by common underlying factors.
      CONCLUSIONS: Nutrition interventions aimed at improving adolescents' food habits
      should target high television-viewers. Our findings underline the importance of
      tackling socio-demographic differences.

PMID- 17176652
TI  - Understanding recent trends in Swiss ambulatory care utilization when out-of
      pocket payment is minimal.
AB  - OBJECTIVE: To examine trends in ambulatory care utilization when individuals face
      almost no financial barriers to health care. METHODS: Observational study of
      insurance data. Adults with minimal deductible were included. Ambulatory care
      visits and costs were measured from 1997 to 2002. RESULTS: Mean ambulatory care
      costs/insuree increased from 1292.- to 1790.- CHF, corresponding to higher
      increases in drug costs (+61.7 %) than services costs (+24.3 %). The proportion
      of visits to generalists decreased while those to hospital outpatient services
      increased. CONCLUSIONS: In a demographically stable population of insurees,
      increases in ambulatory care costs were due neither to growth in physicians'
      visits nor to increasing physicians' fees per act, but to what was included in or
      prescribed during the visits.

PMID- 17176653
TI  - From Ottawa to Bangkok.

PMID- 17176654
TI  - The Bangkok Charter for Health Promotion in a globalized world.

PMID- 17176655
TI  - [Swiss School of Public Health: Master of advanced studies in pharmaceutical
      economics and policy (MPEP)].

PMID- 17176656
TI  - Risk perception and acceptance--one process or two? The impact of aspirations on
      perceived risk and preferences.
AB  - The experiments discussed here are aimed at determining whether risk perception
      and risk acceptance are two distinct psychological processes. This study is
      motivated by the idea of a double-criterion model of choice. In particular, in
      line with risk-value (R-V) models, in which risk is treated as a primitive, it is
      tested whether risk is independent of aspirations and whether preferences depend
      on aspirations. In two experiments, 305 university students were presented with
      pairs of risky projects and were asked to compare their riskiness and select one.
      The aspiration level, defined as the target return on the project, was set
      through an explicit instruction. In Experiment 1, a within-subject designwas
      applied, and thus aspirations were set at two different levels. In Experiment 2,
      with a between-subject design, two different aspiration levels were set for each
      group. The results indicate that risk ordering is insensitive to changes in
      aspirations, but preferences are sensitive to those changes. This supports
      distinctness of risk perception and risk acceptance. The findings are discussed
      in terms of the CPT and SP/A models and the R-V approach. It appears that double
      criterion models provide better and psychologically sounder predictions of
      subjects' preferences.

PMID- 17176657
TI  - Current task activation predicts general effects of advance preparation in task
      switching.
AB  - Two experiments investigated the way that beforehand preparation influences
      general task execution in reaction-time matching tasks. Response times (RTs) and
      error rates were measured for switching and nonswitching conditions in a color-
      and shape-matching task. The task blocks could repeat (task repetition) or
      alternate (task switch), and the preparation interval (PI) was manipulated within
      subjects (Experiment 1) and between-subjects (Experiment 2). The study
      illustrated a comparable general task performance after a long PI for both
      experiments, within and between PI madipulations. After a short PI, however, the
      general task performance increased significantly for the between-subjects
      manipulation of the PI. Furthermore, both experiments demonstrated an analogous
      preparation effect for both task switching and task repetitions. Next, a
      consistent switch cost throughout the whole run of trials and a within-run
      slowing effect were observed in both experiments. Altogether, the present study
      implies that the effects of the advance preparation go beyond the first trials
      and confirms different points of the activation approach (Altmann, 2002) to task
      switching.

PMID- 17176658
TI  - Investigating the mechanisms underlying affective priming effects using a
      conditional pronunciation task.
AB  - Recently, using a conditional pronunciation task, De Houwer and Randell (2004)
      reported evidence of affective priming effects only when pronunciation depended
      on the semantic category of targets. Although these findings support the notion
      that spreading of activation is the mechanism underlying affective priming
      effects, an explanation in terms of postlexical mechanism could not be ruled out.
      To clarify this point, we conducted two experiments in which nouns for both the
      to-be-pronounced as well as the not-to-be pronounced targets were used and all
      stimuli were affectively valenced words. In Experiment 1, the to-be-pronounced
      targets were object-words, and the not-to-be-pronounced targets were person
      words, whereas in Experiment 2, the instructions were reversed. Results of
      experiment 1 showed affective priming effects only when pronunciation of target
      words was conditional upon their semantic category. Most importantly, affective
      priming effects were observed for both object-words (Experiment 1) and person
      words (Experiment 2). These results are compatible with a spreading activation
      account, but not with a postlexical mechanism account of affective priming
      effects in the pronunciation task.

PMID- 17176659
TI  - What makes multiplication facts difficult. Problem size or neighborhood
      consistency?
AB  - Two current models of arithmetic fact retrieval, the network interference theory
      (NIT; Campbell, 1995) and the interacting neighbors (IN) model (Verguts & Fias,
      2005a), predict that errors in simple multiplication should be more probable, if
      they include the same digit as the correct result (i.e., if they are
      "consistent," compared with "inconsistent" errors). In a reanalysis of error data
      originally reported by Campbell (1997), we provide first empirical evidence for
      this prediction. Furthermore, these results support the notion of different
      quantity representations for decades and units as proposed by Nuerk, Weger, and
      Willmes (2001). However, the NIT and IN-model differ in their explanations of the
      problem-size effect, a hallmark finding robustly observed in arithmetic fact
      retrieval. Only the IN-model predicts that a correct answer's neighborhood
      consistency can fully account for the problem-size effect, which was confirmed in
      our analysis.

PMID- 17176660
TI  - Single-attribute implicit association tests (SA-IAT) for the assessment of
      unipolar constructs. The case of sociosexuality.
AB  - A major problem with Implicit Association Tests (IATs) is that they require
      bipolar attributes (e.g., good-bad). Thus, IAT effects for an attribute category
      can be interpreted only relative to an opposite category. Problems arise if there
      is no clear opposite category; in this case, a neutral category can be used,
      although it induces systematic error variance and thus reduces validity. The
      present study suggests that this problem can be solved using single-attribute
      IATs (SA-IATs). Sociosexuality (the tendency to engage in uncommitted sex) was
      expected to be related at the implicit level to stronger stranger-sex
      associations relative to partner-sex associations. An IAT was constructed that
      used conversation as a neutral attribute; it showed satisfactory reliability but
      only low correlations with explicit sociosexuality. An alternative SA-IAT with
      sex as the only attribute showed a similar reliability but higher correlations
      with explicit sociosexuality.

PMID- 17176662
TI  - Event-based prospective memory for poorly attended events.
AB  - In the most frequently used paradigm for studying event-based prospective memory
      (PM, Einstein & McDaniel, 1990), participants perform an ongoing task and are
      asked to perform an additional task when a particular stimulus (the PM cue) is
      presented. In this study three experiments examined how PM performance depends on
      stimulus selection, which is a major process involved in executive task control
      according to current theorizing. Participants made semantic judgments about a
      target word accompanied by two nontargets (distracters). The target was indicated
      by its spatial position (Experiment 1) or color (Experiment 2). The findings
      indicated that PM performance was much poorer when the PM cue was irrelevant to
      the ongoing task, in spite of the fact that nontargets were processed
      semantically as shown in Experiment 3.

PMID- 17176661
TI  - A test of the salience asymmetry interpretation of the alcohol-IAT.
AB  - Abstract. K. Rothermund and D. Wentura (2004) showed how Figure-Ground (FG)
      asymmetries produce effects on the Implicit Association Task (IAT), independent
      of associations. Here, the FG account was tested for the robust finding that
      drinkers show a negative alcohol-IAT effect while being positive on explicit
      measures. FG asymmetries were manipulated through familiarity of alcohol-IAT
      target categories and were assessed with visual search tasks. Supporting the FG
      account, the familiarity manipulation influenced the IAT effect in the expected
      direction, and the IAT effect correlated with FG asymmetries. Contrary to the FG
      account, however, the IAT effect was not reversed, and IAT effects were predicted
      by alcohol use but not by FG asymmetries. Hence, the FG account only partly
      explains the negative alcohol-IAT effect.

PMID- 17176663
TI  - Do transposed-letter similarity effects occur at a syllable level?
AB  - One key issue for any computational model of visual word recognition is the
      choice of an input coding scheme for assigning letter position. Recent research
      has shown that transposed-letter similarity effects occur even when the
      transposed letters are not adjacent (caniso-casino; Perea & Lupker, 2004, JML).
      In the present study we conducted two single-presentation lexical decision
      experiments to examine whether transposed-letter effects occur at a syllable
      level. We tested two types of nonwords: (1) nonwords created by transposing two
      internal CV syllables (PRIVEMARA; the base word is primavera, the Spanish for
      spring) and (2) nonwords created by transposing two adjacent bigrams that do not
      form a syllable (PRIMERAVA). We also created the appropriate orthographic control
      conditions, in which the critical letters were replaced instead of being
      switched. Results showed that the transposition of two syllables or two adjacent
      bigrams produced a quite robust (and similar) transposed-letter effect. Thus,
      transposed-letter effects seem to occur at an early orthographic, graphemic
      level, rather than at a syllable level. We examine the implications of the
      observed results for the input coding schemes in visual word recognition.

PMID- 17176664
TI  - The comparator theory fails to account for the selective role of within-compound
      associations in cue-selection effects.
AB  - In a human causal learning experiment, we investigated cue selection effects to
      test the comparator theory (Denniston, Savastano, & Miller, 2001; Miller &
      Matzel, 1988). The theory predicts that the occurrence of cue selection is
      independent of whether the relevant learning trials are presented in a standard
      forward manner or in a backward manner and that within-compound associations are
      of equal importance in both cases. We found that the strength of the cue
      selection effect was positively correlated with knowledge of within-compound
      associations in the backward condition but not in the forward condition.
      Furthermore, cue-selection effects were less pronounced in the former than in the
      latter condition. These results are at variance with the comparator hypothesis
      but are in agreement with a modified associative theory and with the suggestion
      that retrospective revaluation might be due to rehearsal processes.

PMID- 17176665
TI  - Employment-based retirement plan participation: geographic differences and
      trends, 2005.

PMID- 17176666
TI  - Influence of transcranial magnetic stimulation on spike-wave discharges in a
      genetic model of absence epilepsy.
AB  - Transcranial magnetic stimulation (TMS) impulses, (0.5 Hz, 3 impulses) were
      presented at threshold intensity to male WAG/Rij rats. One group received
      stimuli, which involved motor responses of hindlimbs, rats of the second group
      received sham stimulation. Electrocorticograms (ECoG) were recorded before and up
      to 2 hr from the moment of transcranial magnetic stimulation. It was established
      that such stimulation engendered a reduction of spike-wave discharge (SWD) bursts
      duration. This effect was most pronounced in 30 min from the moment of cessation
      of stimulation, when a decrease of 31.4% was noted in comparison with sham
      stimulated control group. The number of bursts of spike-wave discharges was
      reduced, but did not reach significant difference when compared both with pre
      stimulative base-line level and with sham-stimulated control rats. Bursts of
      spike-wave discharges restored up to pre-stimulative level in 90-150 minutes from
      the moment of cessation of transcranial stimulation. It can be concluded that
      transcranical magnetic stimulation possessed an ability to engender short-time
      suppression of bursts of spike-wave discharges in WAG/Rij rats.

PMID- 17176667
TI  - PEG-induced fusion of phosphatidylcholine-liposomes with protoplasts and post
      fusion evaluation of plating efficiency and enrichment in plasmamembrane
      phosphatidylcholine of protoplasts in Datura innoxia Mill.
AB  - Liposomes entrapping fluorescein diacetate were fused with protoplasts of Datura
      innoxia Mill by employing polyethylene glycol (PEG) as the fusogen. Factors that
      influence liposome-protoplast fusion were optimized as a function of PEG
      concentration and incubation duration, liposome composition and surface charge
      and liposome:protoplast ratio. Phosphatidylcholine-liposomes were found ideal for
      the objectives of the study. Fusion index based on per cent fluorescing
      protoplasts varied among the protoplast types. PEG-incubation duration in the
      fusion assay and growth ability of protoplasts to form microcalli subsequent to
      liposome-protoplast fusion was determined based on protoplast plating-efficiency.
      Plating efficiency of post-fusion protoplasts increased due to incorporation of
      liposome-phosphatidylcholine in the plasmamembrane of protoplasts. Results are
      discussed in relation to the application of liposome-protoplast fusion system in
      selective modification of plasmamembrane phospholipids of protoplasts.

PMID- 17176668
TI  - Effects of oxidizing and reducing agents on ovine pulmonary artery responses to
      nitric oxide donors, sodium nitroprusside and 3-morpholino-sydnonimine.
AB  - Nitrovasodilators-sodium nitroprusside (SNP; 10(-9)-10(-4) M) and 3-morpholino
      sydnonimine (SIN-1; 10(-9)-10(-4) M) produced concentration-dependent relaxation
      of the fourth generation sheep pulmonary artery, preconstricted with 5
      hydroxytryptamine (1 microM). Oxidizing agents [oxidized glutathione (GSSG, 1 mM)
      and CuSO4 (5 and 20 microM)] and reducing agents [dithiothreitol (DTT, 0.1 mM),
      ascorbic acid (1 mM) and reduced glutathione (GSH, 1 mM)] caused opposite effects
      on nitric oxide (NO)-induced vasodilation in the artery. Ascorbic acid and GSH
      potentiated the NO responses, while GSSG and CuSO4 inhibited relaxation caused by
      the nitrovasodilators. DTT, however, reduced the relaxant potency and efficacy of
      SNP and SIN-1. Pretreatment of the pulmonary artery strips with DTT (0.1 mM)
      inhibited SNP (10 microM)-induced Na(+)-K(+)-ATPase activity, while ascorbic acid
      (1 mM) and GSH (1 mM) had no effect either on basal or SNP (10 microM)-stimulated
      86Rb uptake, an index of Na(+)-K(+)-ATPase activity, in ovine pulmonary artery.
      The results suggest that reducing agents like ascorbic acid may have beneficial
      effect in improving the vascular function under oxidative stress.

PMID- 17176669
TI  - Effect of gold on stimulation of reproductive function in immature female albino
      rats.
AB  - Significant increase in ovarian and uterine weight and stimulation of ovarian
      delta5-3beta-hydroxysteroid dehydrogenase (delta5-3beta-HSD) activity and
      elevation of serum estradiol level were observed following gold chloride (0.2
      mg/kg body weight/day), s.c. administration in immature female albino rats.
      Moreover, normal cyclic changes of estrus were found in vaginal smears of these
      rats whereas the rats of other groups showed diestrus phase throughout the period
      of experiment. Histological study of ovary also showed Graafian follicle with
      ovum in rats treated with 0.2 mg/kg/day of gold proving stimulation of
      reproductive function, which was not found in the ovarian histological study of
      other groups including controls. Thus, the results suggest a significant
      stimulatory effect of gold chloride on female reproductive activity in immature
      rats. Further, since the above-mentioned changes were evident at a specific dose
      of gold chloride, the data may have some clinical implications on stimulation and
      enhancement of fertility in immature female rats.

PMID- 17176670
TI  - Impact of feeding ethanolic extract of root bark of Cananga odorata (Lam) on
      reproductive functions in male rats.
AB  - The 50% ethanolic extract of the root bark of C. odorata administered orally at
      the dose of 1g/kg body weight/day for 60 days resulted in decreased epididymal
      sperm motility and sperm count in male albino rats. Morphological abnormalities
      were also observed in the sperms. The testicular glycogen, the activities of
      3beta hydroxy steroid dehydrogenase, glucose 6-phosphate dehydrogenase, malic
      enzyme, sorbitol dehydrogenase in seminal vesicle, fructose in seminal plasma and
      serum testosterone were significantly decreased in treated group. While
      testicular cholesterol level, the concentration of the fecal bile acids, urinary
      excretion of 17 ketosteroids, the activities of 17beta hydroxy steroid
      dehydrogenase, epididymal lactate dehydrogenase and that of testicular HMG CoA
      reductase were increased in treated group when compared to control. The results
      suggest that the ethanolic extract of C. odorata possesses the spermatotoxic
      effects in male albino rats.

PMID- 17176671
TI  - Effect of Aerva lanata on calcium oxalate urolithiasis in rats.
AB  - Calcium oxalate (CaOx) stone was induced in rats using 0.75% of ethylene glycol
      in drinking water for 28 days. Ethylene glycol treated rats showed significant
      increase in the activities of oxalate synthesizing enzymes such as glycolic acid
      oxidase (GAO) in liver and lactate dehydrogenase (LDH) in liver and kidney. CaOx
      crystal deposition, as indicated by increased excretion of stone-forming
      constituents in urine, such as calcium, oxalate, uric acid, phosphorus and
      protein and decreased concentration of inhibitors, such as citrate and magnesium
      was observed in ethylene glycol induced urolithic rats. Histopathological studies
      also confirmed the deposition of CaOx crystals. Administration of Aerva lanata
      aqueous suspension (2g/kg body wt/dose/day for 28 days) to CaOx urolithic rats
      had reduced the oxalate synthesizing enzymes, diminished the markers of crystal
      deposition in the kidney. The results of the present study confirmed that A.
      lanata can be used as an curative agent for urolithiasis.

PMID- 17176673
TI  - In vitro antioxidant studies of Sphaeranthus indicus (Linn).
AB  - The free radical scavenging potential of the plant S. indicus was studied by
      using different antioxidant models of screening. The ethanolic extract at 1000
      microg/ml showed maximum scavenging of the radical cation, 2,2-azinobis-(3
      ethylbenzothiazoline-6-sulphonate) (ABTS) observed upto 41.99% followed by the
      scavenging of the stable radical 1,1-diphenyl, 2-picryl hydrazyl (DPPH) (33.27%),
      superoxide dismutase (25.14%) and nitric oxide radical (22.36%) at the same
      concentration. However, the extract showed only moderate scavenging activity of
      iron chelation (14.2%). Total antioxidant capacity of the extract was found to be
      160.85 nmol/g ascorbic acid. The results justify the therapeutic applications of
      the plant in the indigenous system of medicine, augmenting its therapeutic value.

PMID- 17176672
TI  - Antihyperglycemic, antistress and nootropic activity of roots of Rubia cordifolia
      Linn.
AB  - Effect of alcoholic extract of roots of Rubia cordifolia was studied on elevated
      blood glucose level in alloxan treated animals. The extract reduced the blood
      sugar level raised by alloxan. Effect of alcoholic extract was also investigated
      on cold restraint induced stress and on scopolamine-induced memory impairment.
      Alcoholic extract enhanced brain gamma-amino-n-butyric acid (GABA) levels and
      decreased brain dopamine and plasma corticosterone levels. Acidity and ulcers
      caused due to cold restraint stress were inhibited by alcoholic extract. Animals
      treated with alcoholic extract spent more time in open arm in elevated plus maze
      model. It also antagonized scopolamine induced learning and memory impairment.
      Baclofen induced catatonia was potentiated by alcoholic extract.

PMID- 17176674
TI  - Cytogenetic effects of a mixture of selected metals following subchronic exposure
      through drinking water in male rats.
AB  - The current study examines the genotoxic effects of subchronic exposure via
      drinking water to a mixture of eight metals (arsenic, cadmium, lead, mercury,
      chromium, nickel, manganese and iron) found as contaminants of water sources in
      different parts of India and its possible association with oxidative stress. Male
      rats were exposed to the mixture at 0, 1, 10 and 100 times the mode concentration
      of each metal daily for 90 days. Another dose group at concentration equivalent
      to maximum permissible limit (MPL) for each metal and a reference group given ip
      cyclophosphamide were incorporated. The mixture at 100x level significantly
      increased chromosomal aberrations and micronuclei induction (2.4 folds) in bone
      marrow cells and reduced the ratio of polychromatic to normochromatic
      erythrocytes by 25%. The mixture significantly increased sister chromatid
      exchange in bone marrow (1.67 and 2.3 folds) and spleen (1.57 and 1.98 folds)
      cells with both 10x and 100x doses. Cyclophosphamide was more potent than the
      mixture in causing cytogenetic damage in these parameters. In rat spleen, the
      mixture at 10x and 100x doses caused dose-dependent increase in lipid
      peroxidation (25.95 and 52.71%) and decrease in the activities of superoxide
      dismutase (20.36 and 40.62%), catalase (18.24 and 35.50%), glutathione peroxidase
      (22.33 and 36.12%) and glutathione reductase (19.22 and 31.35%) and in the level
      of GSH (19.76 and 35.15%). The results suggest that the mixture induced
      genotoxicity in rat bone marrow and spleen cells at concentrations relatively
      higher than that found in groundwater sources and the genotoxic effect could
      relate to induction of oxidative stress. However, observations with lower doses
      indicate that additive or synergistic interactions following exposure to metal
      components at MPL levels or at mode concentrations of contemporary groundwater
      levels in India may not result in clastogenicity in male rats.

PMID- 17176675
TI  - Phage typing of indigenous soybean-rhizobia and relationship of a phage group
      strains for their asymbiotic and symbiotic nitrogen fixation.
AB  - A total of 354 indigenous bradyrhizobia were isolated from soybean nodules
      collected from five major crop grown regions. Host-specific 12 phages, each
      active on particular strains were selected. Factors, which influence the
      interaction between the host and phage, were examined. Four different types of
      plaques were detected. Nearly 17% of isolates were found resistant to all phages.
      Phage sensitivity patterns revealed a total of 32 distinct phage genotype groups.
      Different set of phage combinations expressed variation in specificity for
      parasitizing against particular group of rhizobia. Distributions of isolates in
      each phage types differed markedly between regions. Interestingly, nine strains
      belonging to phage group 16 exhibited high ex planta nitrogenase activity in
      culture. However, no correlation could be established between high ex planta
      nitrogenase activity and their symbiotic effectiveness with soybean cultivars.
      Soybean cv. JS335 showed relatively superior performance than Bragg and Lee with
      indigenous bradyrhizobial strains. Phage typing revealed the existence of large
      genetic diversity among native rhizobia and selection of the superior
      bradyrhizobial strains can also be possible for a given soil-climate-cultivar
      complex.

PMID- 17176676
TI  - Isoflavonoids production in callus culture of Pueraria tuberosa, the Indian
      kudzu.
AB  - Isoflavonoid contents of different plant parts and callus tissues of the Indian
      Kudzu, Pueraria tuberosa (Roxb.ex.Willd.) DC are presented. The initial cultures
      were slow growing, associated with browning of the tissues. The production of
      four isoflavonoids (puerarin, genistin, genistein and daidzein) in the callus
      cultures of P. tuberosa was studied by manipulating the plant growth regulators
      and sucrose concentration in the medium. Organogenesis was not recorded in callus
      on any of these treatments. Tuber and stem accumulated puerarin, a glycoside of
      daidzein, at high amounts, 0.65% and 0.054% respectively. However, the daidzein
      content of the callus tissues grown on Murashige and Skoog medium containing BA
      (20.9 microM) and sucrose (60 gl(-1)) was significantly higher (0.056%) than in
      vivo plant material (0.02%) and other comparable culture systems like Genista and
      Pueraria lobata.

PMID- 17176677
TI  - Affinity purification and partial characterization of IgM-like immunoglobulins of
      African catfish, Clarias gariepinus (Burchell, 1822).
AB  - IgM like macroglobulin from bovine serum albumin (BSA)-immunized African catfish
      C. gariepinus was purified by affinity chromatography and partially
      characterized. The molecular weight of this macroglobulin was 840 kDa, as
      estimated by gel filtration chromatography. Purified macroglobulin was analyzed
      using SDS-PAGE under reducing and non-reducing conditions. The molecular weight
      (MW) of heavy and light chain was 74.8 kDa and 27.2 kDa respectively, in presence
      of a reducing agent. In non-reducing SDS-PAGE, a single high MW band was observed
      representing tetrameric form.

PMID- 17176678
TI  - Antigenic competition among different 'O' antigens of Salmonella enterica
      subspecies enterica serovars during hyperimmunization in pony mares.
AB  - The present study on antigenic competition among somatic 'O' antigens of
      different Salmonella groups (A, B, C1, C2, D and E1) in mares revealed that the
      immune response to most of the antigens was not (A, B, C2) or little (C1, D)
      affected by antigenic competition. However, E1 group antigen, which induced high
      antibody titres (Avg. 12967.3) when given alone, produced almost 3.5 log2 lower
      antibody titres on giving with other antigens, indicating the antigenic
      competition among some Salmonella group antigens. The antigenic competition
      varied for different antigens even of the similar chemical nature. Therefore,
      antigens belonging to different somatic groups should not be given together for
      the purpose of raising polyvalent serum or for immunization using multivalent
      Salmonella vaccines prepared from strains of different 'O' groups revealing
      antigenic competition.

PMID- 17176679
TI  - Physician perceptions of pharmacist provision of outpatient medication therapy
      management services.

PMID- 17176681
TI  - Quality measurement: time to get serious.

PMID- 17176680
TI  - Collaborative research: benefits for all involved.

PMID- 17176682
TI  - Medication therapy management services: assessing year 1, gauging year 2.

PMID- 17176683
TI  - Survey of medication therapy management programs under Medicare part D.
AB  - OBJECTIVE: To describe and summarize the enrollment criteria and benefit designs
      for medication therapy management (MTM) programs offered throughout the United
      States during the first year of the Medicare Part D benefit. DESIGN: Cross
      sectional survey. SETTING: United States between November 1, 2005, and June 30,
      2006. PARTICIPANTS: MTM benefit plan managers of major health insurance companies
      nationwide selected nonrandomly by the investigators from lists provided by the
      Centers for Medicare & Medicaid Services. INTERVENTION: Telephone interview
      and/or e-mail 12-item survey with mostly open-ended questions. MAIN OUTCOME
      MEASURES: Characteristics required for a patient to be enrolled in MTM programs
      and types of services provided along with modes of delivery. RESULTS: Interviews
      were completed or surveys returned from 21 distinct MTM programs representing 70
      health insurance plans covering 12.1 million Medicare enrollees. Of the MTM
      programs offered, 90.5% restricted their enrollment based on number of diseases,
      with a median of 3 (range, 2-5) diseases required; 57.1% restricted enrollment
      based on the type of chronic condition; and 95.2% had requirements for the number
      of medications (median, 6; range, 2-24) necessary for enrollment in the program.
      The most frequently provided MTM services were patient education (75.0% of
      programs),patient adherence (70.0%), and medication review (60.0%). The median
      number of different service types provided by MTM programs was 3 (range, 2-7).
      MTM program services included the use of mailed interventions (76.1%) and inhouse
      call centers (90.4%). While only 4 of the 21 MTM programscontracted with
      pharmacies to provide some or all of their MTM services, these plans covered a
      large number of beneficiaries (7.5 million lives). CONCLUSION: MTM programs
      offered by prescription drug plans and Medicare Advantage plans were highly
      variable during the first year of the Medicare Part D benefit. Definitive
      evidence supporting the effectiveness of many of the most common interventions is
      lacking.

PMID- 17176684
TI  - Medication therapy management survey of the prescription drug plans.
AB  - OBJECTIVE: To evaluate the preliminary development and implementation plans for
      medication therapy management (MTM) services across plan sponsors for the
      Medicare Part D Prescription Drug Plans (PDPs) and provide pharmacists with
      insights for MTM development. DESIGN: Cross-sectional survey. SETTING: United
      States. PARTICIPANTS: 307 individual contacts from Medicare Advantage or stand
      alone PDPs. INTERVENTION: A survey comprising questions about the PDP
      demographics, plans and implementation, beneficiary eligibility criteria, scope
      of services, providers of services, and payment structure for MTM services was e
      mailed and mailed in November 2005. MAIN OUTCOME MEASURES: Descriptive and
      bivariate analysis of survey items. RESULTS: A total of 97 usable surveys were
      completed, a 31.5% response rate. Almost all respondents had a plan in place for
      MTM services. The majority of PDPs perceived that MTM would have a moderate
      benefit to their organization. Most PDPs planned to focus efforts on diabetes,
      heart failure, and other forms of cardiovascular disease. Overwhelmingly, PDPs
      planned to follow the Centers for Medicare & Medicaid Services (CMS) mandate for
      criteria regarding beneficiary eligibility. Only 8.2% of respondents planned to
      use a "traditional" pharmacist, such as a community, long-term care, hospital, or
      clinic pharmacist. The majority of PDPs (53.6%) planned to employ managed care
      pharmacists to administer MTM services. CONCLUSION: Pharmacists are eager to
      implement MTM services and are looking for PDPs to provide a path of
      implementation and reimbursement. Many PDPs were planning to deliver MTM services
      internally using health professional staff, thereby limiting the extent of
      participation of community, long-term care, hospital and health-system, and
      clinic-based pharmacists. Further research and advocacy are required to ensure
      that MTM services accomplish the true intent of the congressional and CMS
      mandates.

PMID- 17176685
TI  - Medication therapy management services in North Carolina community pharmacies:
      current practice patterns and projected demand.
AB  - OBJECTIVE: To evaluate the types of cognitive services offered and the number of
      patients being served in community pharmacies, determine the number of pharmacies
      that plan to offer medication therapy management (MTM) services under the
      Medicare Part D prescription drug benefit, and assess whether current and
      expected practices will meet the potential needs of enrollees. DESIGN: Cross
      sectional study. SETTING: North Carolina in January 2005. PARTICIPANTS: 1,593
      community pharmacy managers. INTERVENTIONS: Survey using a Web-based tool. MAIN
      OUTCOME MEASURES: Provision of cognitive services and number of patients for whom
      services are provided. RESULTS: A total of 262 (16%) pharmacy managers provided
      usable responses. Approximately 42% of respondents (n = 110) indicated that they
      provide some type of cognitive service. Comprehensive MTM services, or services
      consistent with the professionwide consensus definition, were provided by 31% of
      respondents (n = 81). Independent pharmacies were more likely to offer some type
      of service compared with chain pharmacies (58% versus 31%, respectively; P <
      .001). Pharmacy managers with a doctor of pharmacy degree were less likely than
      pharmacy managers with a bachelor's degree to offer services in their pharmacies
      (P = .02), and pharmacies with pharmacists on staff who had received certificate
      training were more likely to offer cognitive services (P = .03). Of all
      respondents, 28% (n = 73) indicated that they planned to offer MTM services under
      the Medicare Part D prescription drug benefit. CONCLUSION: Comparing these
      results with those of a 1999 survey of North Carolina pharmacists that used some
      of the same items, the percentage of community pharmacies that provide cognitive
      services has increased in the intervening years but remains low. Among the
      services being offered in 2005, most were focused on patient education and
      training, coordinating and integrating care, and medication regimen reviews.
      Implementation of MTM services under the Medicare Part D prescription drug
      benefit should hasten the development and offering of these services in community
      pharmacies.

PMID- 17176686
TI  - Community and ambulatory pharmacy: evaluation of patient care services and
      billing patterns before implementation of Medicare part D.
AB  - OBJECTIVE: To provide a summary of community and ambulatory pharmacy practice and
      billing patterns for medication therapy management services before implementation
      of Medicare Prescription Drug Improvement and Modernization Act of 2003 (MMA).
      DESIGN: Cross-sectional survey. SETTING: Ambulatory care and community pharmacy
      practice settings in the United States in January 2004. PARTICIPANTS: Members of
      the American College of Clinical Pharmacy Ambulatory Practice and Research
      Network, preceptors of the American Pharmacists Association (APhA) Community
      Pharmacy Residency Programs, and participants in the APhA Immunizing Pharmacist
      listserv. INTERVENTIONS: E-mail invitations to participate in a Web-based survey.
      MAIN OUTCOME MEASURES: Practice setting; pharmacy services performed; whether
      pharmacists were billing for pharmacy services; if billing, the billing technique
      used; if not billing, the reason for not billing. RESULTS: Of 349 respondents,
      127 (36.4%) were practicing within a physician office, while 121 (34.7%) were
      practicing in community pharmacies. Diabetes, anticoagulation, dyslipidemia,
      hypertension, and smoking cessation management services were performed
      significantly more often in physician offices. Immunization delivery and
      diabetes, dyslipidemia, and osteoporosis screenings were performed significantly
      more often in community settings. A total of 190 (54.5%) pharmacists stated that
      they were billing for pharmacy services. More community pharmacists were billing
      for services compared with other combined practice settings (69.2% versus 46.7%,
      P < .001). Top reasons identified for not billing for services were salaried
      position, indigent population, and discomfort with the billing process.
      CONCLUSION: Valuable baseline data are provided regarding pharmacy services that
      have been successfully implemented in ambulatory and community practice settings
      and which billing techniques were used to receive reimbursement before the
      implementation of MMA.

PMID- 17176687
TI  - Iowa medicare beneficiaries' satisfaction and experiences with a prescription
      drug discount card and preferred drug list.
AB  - OBJECTIVE: To evaluate the expectations, experiences, and satisfaction with the
      Iowa Priority Prescription Savings (IPPS) program. DESIGN: Longitudinal
      descriptive study. SETTING: Iowa. PARTICIPANTS: Randomly selected Iowa Medicare
      beneficiaries who self-enrolled in the IPPS prescription discount card program.
      INTERVENTIONS: Three self-administered surveys mailed in November 2002, June
      2003, and September 2004, during the first, second, and third years of IPPS
      operation. MAIN OUTCOME MEASURES: Expectations of drug discounts, amount of
      discounts received, awareness of the IPPS preferred drug list (PDL), and
      satisfaction with the program. RESULTS: Usable response rates for the three
      surveys were 43.5%, 31.0%, and 38.4%. About one fourth of members initially
      expected discounts of more than 20% on their prescription medications. After IPPS
      was implemented, many members were unaware of the discounts they were receiving,
      but the percentage of members reporting discounts of more than $20 per month
      increased from 7.4% in year 1 to 16.4% in year 3. More than one half of the
      members were unaware of which drugs were on the PDL in years 1 and 2, but this
      improved to 21% unawareness in year 3. Satisfaction with the program was low but
      improved over time. Members who received discounts, did not expect large
      discounts, or received a medication review were more satisfied with the program.
      CONCLUSION: Some IPPS members had unrealistic expectations about the amount of
      discounts they would receive, and expectations of large discounts decreased
      satisfaction. Satisfaction and amount of discounts improved over time, and
      beneficiaries whose medications were reviewed, usually by a pharmacist, were more
      satisfied with the program. PDL awareness was a problem despite substantial
      educational efforts by IPPS, a finding that has implications for the recently
      implemented Medicare Part D drug benefit.

PMID- 17176688
TI  - Pharmacy placement of nonprescription nicotine replacement therapy products and
      community pharmacists' counseling for product use.
AB  - OBJECTIVE: To investigate the relationship between nonprescription nicotine
      replacement therapy (NRT) product placement within community pharmacies and the
      number of patients whom pharmacists report counseling for use of these products.
      DESIGN: Cross-sectional study. SETTING: Four Northern California counties.
      PARTICIPANTS: 327 community pharmacists. INTERVENTIONS: Survey mailed in 1999
      2000. MAIN OUTCOME MEASURES: Estimated number of NRT purchasers who received
      counseling in their pharmacy and pharmacists' level of control over NRT purchases
      and counseling as functions of the location of the NRT products within the
      pharmacy setting. RESULTS: Of 327 community pharmacists surveyed, 26 (8.0%)
      reported that all nonprescription NRT products were stocked behind the pharmacy
      counter (full control over NRT purchases and counseling), 46 (14.1%) reported
      that all NRT products were stocked outside of the pharmacy department in an area
      that could not be seen easily by the pharmacist (no control), and the remainder
      (n = 255; 78.0%) indicated that all NRT products were located within their visual
      field but not behind the counter and/or that NRT products were located in more
      than one of the three previously described store locations (i.e., behind counter,
      not behind counter but within visual field, and outside visual field) (partial
      control). While adjusting for known confounders (pharmacists' self-efficacy for
      counseling, practice setting, and perceived pros of counseling), NRT product
      location was significantly associated with counseling of four or more patients a
      month for use of these products (P = .005). Specifically, compared with
      pharmacists with no control over NRT purchases and counseling, pharmacists with
      full control were 4.73 (95% CI, 1.46-15.37) times as likely to counsel four or
      more patients per month, and pharmacists with partial control were 2.95 (95% CI,
      1.47-5.94) times as likely. Compared with pharmacists with partial control,
      pharmacists with full control were 1.60 (95% CI, 0.58-4.41) times as likely to
      counsel at least four patients monthly (P = .361). CONCLUSION: The location of
      nonprescription NRT products within the community pharmacy setting is associated
      with the number of patients whom pharmacists report counseling for use of these
      products.

PMID- 17176689
TI  - Pharmacists' smoking cessation practices: relationship to their knowledge and
      skills, attitudes, and perceptions of roles.
AB  - OBJECTIVE: To assess factors associated with pharmacists' practices regarding
      patients' smoking and smoking cessation. DESIGN: Cross-sectional analysis.
      SETTING: Four Canadian provinces (Ontario, Quebec, Saskatchewan, Prince Edward
      Island). PARTICIPANTS: Practicing community pharmacists (n = 906; weighted n =
      897). INTERVENTION: Population-based mailed questionnaire survey with 72%
      response rate. MAIN OUTCOME MEASURES: Bivariate and multivariate relationships
      between 12 clinical interventions regarding smoking and smoking cessation and 7
      domains: basic pharmacologic knowledge; applied health science knowledge and
      skills; positive, negative and economic-related attitudes toward smoking
      cessation; perceptions of pharmacists' roles with patients who smoke: assessing
      and motivating patients; assisting, referring and following up. RESULTS: Basic
      pharmacologic knowledge and applied health science knowledge and skills were
      independently related to 12 and 10 interventions, respectively. Positive
      attitudes toward smoking cessation were independently related to 8 interventions.
      Negative attitudes and economic-related attitudes toward smoking cessation were
      each independently related to only 1 intervention. Perceptions of pharmacists'
      roles with respect to "assessing and motivating patients," and "assisting,
      referring, and following up" were independently related to 8 and 3 interventions,
      respectively. CONCLUSION: Initiatives to increase tobacco-related knowledge and
      skills and enhance positive attitudes and role perceptions with respect to
      smoking and smoking cessation may promote interventions by community pharmacists
      with patients who smoke.

PMID- 17176691
TI  - Dispensing and administration of radiopharmaceuticals for dacryoscintigraphy.

PMID- 17176690
TI  - The Coulee Region Community Pharmacy Asthma Intervention study.
AB  - OBJECTIVE: To determine whether community pharmacist-initiated interventions
      containing a recommendation to adjust prescribed asthma therapy are more helpful
      to prescribers than similar communications without such a recommendation. DESIGN:
      Prospective, multicenter, quasi-experimental design with posttest. SETTING:
      Wisconsin and Minnesota. PATIENTS AND PARTICIPANTS: 33 community and clinic
      pharmacies throughout the Coulee Region of Wisconsin and Minnesota enrolled
      eligible patients from October 1, 2004, to January 31, 2005. Patients were
      between 12 and 60 years of age, had used three or more short-acting beta-agonist
      (SABA) canisters with-in the previous 90 days, and did not meet any exclusion
      criteria. INTERVENTIONS: Based on an evaluation of each patient's inhaler
      technique and adherence to controller medications, pharmacists sent to the
      prescriber a fax containing a recommendation (for patients with proper technique
      and appropriate adherence to prescribed controller medications) or information
      (for those who had any combination of inappropriate inhaler technique or
      inappropriate adherence). MAIN OUTCOME MEASURE: Health care professionals' yes-or
      no response to the question, "Do you find this form helpful for making clinical
      decisions?" RESULTS: Pharmacists offered to enroll 235 patients who were
      identified as meeting preliminary inclusion criteria. Of those, 112 people met
      exclusion criteria, 28 were not interested in their pharmacists' involvement, 13
      stated that they did not have time to participate, 11 took the forms home but did
      not return them, and 11 other patients were excluded by the pharmacists for other
      reasons. The remaining 60 patients were in enrolled in the study, 60 faxes were
      sent from 16 pharmacies, and 40 of those were analyzed further. For 24
      recommendation faxes sent, prescribers rated 15 as helpful (62.5%) and 4 as not
      helpful (16.7%). Of 16 informational faxes sent, 10 were marked helpful (62.5%)
      and 2 were marked not helpful (12.5%). CONCLUSION: Recommendation and
      informational faxes were overall helpful to health care professionals in making
      clinical decisions. Respondents found the two types of faxed interventions as
      equally helpful, suggesting that pharmaceutical care initiated by community
      pharmacists is helpful to prescribers.

PMID- 17176693
TI  - Edward Robinson Squibb (1819-1900): advocate of product standards.

PMID- 17176692
TI  - Pharmacists' perceptions of controlled substance abuse in the rural upper
      peninsula of Michigan.

PMID- 17176695
TI  - New drugs: ranibizumab, posaconazole, and darunavir.

PMID- 17176694
TI  - Human papillomavirus vaccine: a major public health advance.

PMID- 17176696
TI  - OTC product: band-aid liquid bandage.

PMID- 17176697
TI  - Joint Commission extends date for complying with the electronic statement of
      conditions.

PMID- 17176698
TI  - Joint Commission to implement program-specific tracers in 2007.

PMID- 17176699
TI  - Correction: Leadership chapter and standards applicability grid for ambulatory
      care.

PMID- 17176700
TI  - Joint Commission and National Quality Forum announce the 2006 John M. Eisenberg
      Patient Safety and Quality Awards.

PMID- 17176701
TI  - Revision: Rationale for accreditation participation requirement 10.

PMID- 17176702
TI  - Correction: Standard EC.7.40, Element of Performance 5, for hospital and
      laboratory.

PMID- 17176703
TI  - Correction: Standard LD.3.110, Element of Performance 12, for hospitals.

PMID- 17176704
TI  - Revision: Nursing chapter for critical access hospitals and hospitals.

PMID- 17176705
TI  - Survey results: doctors say morale is hurting.

PMID- 17176706
TI  - Physicians offer prescriptions to boost low morale.

PMID- 17176708
TI  - Secrets of physician satisfaction. Study identifies pressure points and reveals
      life practices of highly satisfied doctors.

PMID- 17176709
TI  - Politics of health care are pulling doctors down.

PMID- 17176707
TI  - Speak up or burn out.

PMID- 17176710
TI  - Five keys to transforming stress into success.

PMID- 17176711
TI  - Reclaiming physician power: your role as a physician executive.

PMID- 17176712
TI  - Reflections from my hips.

PMID- 17176713
TI  - Pay-for-performance program focuses on Web-based quality data.

PMID- 17176714
TI  - Have dream...will prevail.

PMID- 17176715
TI  - Employer-provided health care: where's the justice?

PMID- 17176716
TI  - Worker's compensation 101: a primer for the physician executive.

PMID- 17176717
TI  - Creating customer value propositions.

PMID- 17176718
TI  - Handling emotional reactions to change.

PMID- 17176720
TI  - The new union strategy: Turning the community against you.
AB  - Corporate campaigns are unions' latest--and most aggressive--tactic to recruit
      hospital employees. Learn what they are doing and be forearmed.

PMID- 17176719
TI  - Who will teach the nurses we need?
AB  - Looming as large as the nursing shortage itself, a dwindling supply of nurse
      faculty threatens to exponentially compound the staffing crisis. However, new
      solutions and nursing roles are on the horizon.

PMID- 17176721
TI  - Trustee workbook 4. The re-emerging role of philanthropy in the boardroom.

PMID- 17176722
TI  - Strategic financial planning.
AB  - Successful hospitals and health systems plot a careful and well-thought-out path
      to achieving long-term financial performance stability.

PMID- 17176724
TI  - Leading the drive for quality: Is your board ready?

PMID- 17176725
TI  - Board leadership: Who's in the driver's seat?

PMID- 17176723
TI  - Philanthropy: A new/old board responsibility.

PMID- 17176726
TI  - What senior employees offer.

PMID- 17176730
TI  - Body image, disordered eating and the school environment.

PMID- 17176731
TI  - 'Tis the season for cavity prevention.

PMID- 17176733
TI  - Interactive Web technology provides significant advantages in oral health
      education.

PMID- 17176734
TI  - The American school nurse. Expanding multicultural knowledge. Part 3.

PMID- 17176735
TI  - Real world meal planning strategies for children and adolescents with diabetes.

PMID- 17176737
TI  - Environmentally friendly healthcare design.

PMID- 17176736
TI  - Get S.M.A.R.T. about meningitis. School meningitis awareness resource tools:
      vaccination clinic resource guide.

PMID- 17176738
TI  - Root canal retreatment.
AB  - Root canal therapy is not always successful and an increasing number of patients
      are requesting retreatment to address intraradicular infection. The armamentarium
      available to assist the dentist, some of which is described in this article, has
      never been greater.

PMID- 17176739
TI  - Modern restorative management of patients with congenitally missing teeth: 1.
      Introduction, terminology and epidemiology.
AB  - The management of patients with congenitally missing teeth can be a challenge
      and, in many cases, requires multidisciplinary care. In this four-part series, a
      contemporary approach to managing this group of patients is discussed. This first
      paper examines the terminology, epidemiology and restorative challenges that such
      patients can exhibit.

PMID- 17176740
TI  - Current concepts in the management of oral cancer.
AB  - For patients diagnosed with oral cancer, treatment may involve surgery or
      radiotherapy alone, or a combination of the two. Where radiotherapy is the sole
      modality, the addition of chemotherapy may be beneficial, particularly with
      advanced tumours. If the treatment is surgery, this may involve extensive
      microsurgical reconstruction. Follow up of treated patients should be rigorous
      and, ideally, quality of life should be measured.

PMID- 17176741
TI  - Growth modification treatment in class III malocclusions--an orthodontic case
      report.
AB  - A number of treatment options for Class III malocclusions have been reported.
      Early intervention incorporating growth modification allows the clinician to
      attempt mandibular growth restraint and promote the forward growth of the
      maxilla. At the optimal age for growth modification, rapid maxillary expansion
      (RME) and protraction headgear can be used to produce these beneficial changes.
      The following case report describes the management of an 8.5-year-old patient who
      underwent treatment using RME, protraction headgear and fixed appliances.

PMID- 17176742
TI  - The management of abuse: 4. Abuse of vulnerable adults.
AB  - Vulnerable adults include those who, for reasons of age or illness, are unable to
      protect themselves from significant harm. The role of the GDP and the dental team
      in the recognition and management of abuse of vulnerable adults is discussed.
      Information on the current legislation and protocols for referral are provided.

PMID- 17176743
TI  - Foreign body ingestion and aspiration in dentistry: a review of the literature
      and reports of three cases.
AB  - This article reviews several cases of foreign body ingestion or inhalation
      reported in the literature. Prevention, complication and management of this event
      are discussed and three case reports presented. Two of the cases were bridge
      ingestion and one was ingestion of an orthodontic band. The three cases were
      managed by watchful waiting and the ingested foreign bodies came out in the
      stools without complications.

PMID- 17176744
TI  - Physical signs for the general dental practitioner. Case 39. Cafe au lait spots
      due to neurofibromatosis.

PMID- 17176745
TI  - Aspects of human disease. Congenital heart disease.

PMID- 17176746
TI  - Nanotechnology and site-targeted drug delivery.
AB  - Nanotechnology, building on its ability to control or manipulate structures at
      the atomic level, promises to develop effective drug-delivery systems. This is to
      be achieved through creating structures that have novel properties because of
      their small size. This is not an entirely new concept in site-targeted drug
      delivery, and this critical review examines recent contributions made by
      'nanotechnology' to solve critical issues concerning the development of
      therapeutically effective and acceptable site-targeted drug delivery systems. It
      is shown that very little progress has been made. For nanotechnology rationally
      to generate materials useful in human therapy it will need to progress in full
      recognition of all the requirements biology places on the acceptability of
      exogenous materials.

PMID- 17176747
TI  - Interplay of biomaterials and micro-scale technologies for advancing biomedical
      applications.
AB  - Micro-scale technologies have already dramatically changed our society through
      their use in the microelectronics and telecommunications industries. Today these
      engineering tools are also useful for many biological applications ranging from
      drug delivery to DNA sequencing, since they can be used to fabricate small
      features at a low cost and in a reproducible manner. The discovery and
      development of new biomaterials aid in the advancement of these micro-scale
      technologies, which in turn contribute to the engineering and generation of new,
      custom-designed biomaterials with desired properties. This review aims to present
      an overview of the merger of micro-scale technologies and biomaterials in two
      dimensional (2D) surface patterning, device fabrication and three-dimensional
      (3D) tissue-engineering applications.

PMID- 17176748
TI  - Nanobiomaterials: a review of the existing science and technology, and new
      approaches.
AB  - Nanotechnology has made great strides forward in the creation of new surfaces,
      new materials and new forms which also find application in the biomedical field.
      Traditional biomedical applications started benefiting from the use
      nanotechnology in an array of areas, such as biosensors, tissue engineering,
      controlled release systems, intelligent systems and nanocomposites used in
      implant design. In this manuscript a review of developments in these areas will
      be provided along with some applications from our laboratories.

PMID- 17176749
TI  - Synthesis of nanostructured bio-related materials by hybridization of synthetic
      polymers with polysaccharides or saccharide residues.
AB  - In the first part of this review, we describe the synthesis of nanostructured
      hybrid materials composed of polysaccharides and synthetic polymers. Amylose
      synthetic polymer inclusion complexes were synthesized by amylose-forming
      polymerization using phosphorylase enzyme in the presence of synthetic polymers
      such as polyethers and polyesters. Alginate-polymethacrylate hybrid materials
      were prepared by free-radical polymerization of cationic methacrylate in the
      presence of sodium alginate. These methods allow the simultaneous control of the
      nanostructure with polymerization, giving well-defined hybrid materials. In the
      second part of this review, we describe the synthesis of novel glycopolymers with
      rigid structures. Polyaniline-based glycopolymers were synthesized by means of
      oxidative polymerization of N-glycosylaniline. Polysiloxane-based glycopolymers
      were prepared by means of introduction of sugar-lactone to the rodlike
      polysiloxane. These glycopolymers had regular higher-ordered structures due to
      their rigid polymer backbones, resulting in control of the three-dimensional
      array of sugar-residues.

PMID- 17176750
TI  - Nanostructured bio-functional polymer brushes.
AB  - Structured poly(glycidyl methracrylate) (poly-GMA) brushes have been grafted onto
      flexible fluoro-polymer films using a radiation grafting process. The reactive
      epoxide of poly-GMA provides the basis for a versatile biofunctionalization of
      the grafted brushes. Structure definition by extreme ultraviolet (EUV) exposure
      allowed nanometer-scale resolution of periodic patterns. By variation of the
      exposure dose the height of the grafted structures can be adapted in a wide
      range. Derivatization of the grafted brushes included reaction with various
      amines with different side chains, hydrolysis of the epoxide to diols to increase
      protein resistance and introduction of ionic groups to yield poly-electrolytes.
      As an example for biofunctionalization, biotin was linked to the grafted brush
      and biofunctionality was demonstrated in a competitive biotin-streptavidin assay.
      In this article we also present a brief review of other approaches to obtain
      structured biofunctional polymer brushes.

PMID- 17176751
TI  - Antimicrobial polypeptide multilayer nanocoatings.
AB  - A multilayer coating (or film) of nanometer-thick layers can be made by
      sequential adsorption of oppositely charged polyelectrolytes on a solid support.
      The method is known as layer-by-layer assembly (LBL). No special apparatus is
      required for LBL and nanofilms can be prepared under mild, physiological
      conditions. A multilayer nanofilm in which at least one of the constituent
      species is a polypeptide is a polypeptide multilayer nanofilm. The present work
      was aimed at assessing whether polypeptide multilayer nanofilms with specific
      antimicrobial properties could be prepared by incorporation of a known
      antimicrobial agent in the film structure, in this case the edible protein hen
      egg white lysozyme (HEWL). The chicken enzyme is widely employed as a human food
      preservative. An advantage of LBL in this context is that the nanofilm is
      fabricated directly on the surface of interest, eliminating the need to
      incorporate the antimicrobial in other packaging materials. Here, nanofilms were
      made of poly(L-glutamic acid) (PLGA), which is highly negatively charged in the
      mildly acidic pH range, and HEWL, which has a high net positive charge at acidic
      pH. We show that PLGA/HEWL nanofilms inhibit growth of the model microbe
      Microccocus luteus in the surrounding liquid medium. The amount of HEWL released
      from PLGA/HEWL films depends on the number of HEWL layers and therefore on the
      total quantity of HEWL in the films. This initial study provides a sketch of the
      scope for further development of LBL in the area of antimicrobial polypeptide
      multilayer films. Potential applications of such films include strategies for
      food preservation and coatings for implant devices.

PMID- 17176752
TI  - Select bladder smooth muscle cell functions were enhanced on three-dimensional,
      nano-structured poly(ether urethane) scaffolds.
AB  - Bladder wall resection is often required as a treatment for invasive bladder
      cancer. When this happens, a suitable replacement material is needed. The present
      study, therefore, created three-dimensional, porous, nano-structured poly(ether
      urethane) (PU) matrices for use as bladder tissue-engineering scaffolds. Select
      cytocompatibility experiments (specifically adhesion and long-term growth
      studies) were performed on these scaffolds using human bladder smooth muscle
      cells (BdSMCs). In addition, the amount of total collagen and elastin present in
      each cell-seeded scaffold was determined since the production of these
      extracellular matrix (ECM) proteins is essential for the health and survival of
      cells and for the functionality of the replaced organ. Finally, to better
      understand how these scaffolds and resident cells would perform in the complex
      mechanical environment of the bladder wall, scaffolds and cells were subjected to
      10 cmH2O pressure using a computer-controlled pressure chamber. Results provided
      evidence that compared to conventionally used, micro-dimensional PU scaffolds,
      the novel, nanodimensional scaffolds created in this research increased cell
      adhesion, growth, and ECM protein production. Additionally, scaffolds and
      resident cells were not affected by exposure to 10 cmH2O pressure (compared to
      controls maintained under atmospheric conditions). These results are promising
      and provide evidence that the nano-dimensional PU scaffolds created in this
      research are suitable bladder replacement materials that may outperform materials
      currently used for such purposes.

PMID- 17176753
TI  - Mode of action of microbial bioactive metabolites.
AB  - Pathogenic microorganisms can be suppressed by cell wall destruction.
      Biosynthesis of peptidoglycans forming bacterial cell wall is interrupted by
      glycopeptides which inhibit polymerization of a disaccharide formed by N
      acetylglucosamine and N-acetylmuramic acid, beta-lactams and their derivatives
      inhibit peptidoglycan cross-linking. Antibiotics inhibiting protein synthesis
      bind to different sites on the rRNA and interfere with the formation of the
      polypeptide chain. Tumor cells resistant to chemotherapeutic drugs overproduce
      proteins transporting the drugs out of cells; these proteins eliminate substances
      which inhibit transcription of transport proteins. Some antitumor drugs
      (anthracyclines, fluoroquinolones, acridines etc.) act at topoisomerases which
      irreversibly bind to DNA and inhibit DNA synthesis. Immunosuppressants affect
      various components of the immune system such as T-helper, T-effector cell
      function, antigen presentation and B-cell function. Antiparasitics--avermectins-
      bind to a receptor of this Gab-gated chlorine channel in the nerve fiber of
      nematodes and anthropodes, increasing the permeability of the membrane for
      chloride ions; the increased transport of chloride ions into the cell causes the
      death of the parasite. Ionophores dissolve in phospholipid bilayers and
      enormously increase their ionic permeability. Respiration inhibitors block the
      transport of electrons at several places of the respiratory chain. Rifamycin
      binds to the beta subunit of bacterial RNA polymerase, thereby blocking mRNA
      synthesis. Antiviral compounds inhibit the transcription of DNA by several
      mechnisms or by inhibition of viral entry into host cells.

PMID- 17176754
TI  - Adaptive changes in fatty acids of E. coli strains exposed to a quaternary
      ammonium salt and an amine oxide.
AB  - Resistant strains of Escherichia coli were obtained by stepwise cultivation in
      media with increasing concentration of antimicrobially active 1
      (methyldodecyl)dimethylamine oxide and 1-(methyldodecyl)trimethylammonium
      bromide. Adaptive changes were determined in the fatty-acid (FA) composition in
      an isolated lipopolysaccharide sample from the outer membrane of these strains.
      The composition of this FA mixture from adapted strains was compared with that of
      FA from a sensitive strain. The differences were found in level of palmitic,
      heptadecanoic, heptadecenoic, heptadecadienoic and nonadecenoic acids. In
      addition, the adapted strains differed from each other in the content of
      myristic, pentadecanoic, stearic and linoleic acids.

PMID- 17176755
TI  - Pseudomonas aeruginosa inducing rice resistance against Rhizoctonia solani:
      production of salicylic acid and peroxidases.
AB  - Three isolates of Pseudomonas aeruginosa were used for seed treatment of rice;
      all showed plant growth promoting activity and induced systemic resistance in
      rice against Rhizoctonia solani G5 and increased seed yield. Production of
      salicylic acid (Sal) by P. aeruginosa both in vitro and in vivo was quantified
      with high performance liquid chromatography. All three isolates produced more Sal
      in King's B broth than in induced roots. Using a split root system, more Sal
      accumulated in root tissues of bacterized site than in distant roots on the
      opposite site of the root system after 1 d, but this difference decreased after 3
      d. Sal concentration 0-200 g/L showed no inhibition of mycelial growth of R.
      solani in vitro, while at > or =300 g/L it inhibited it. P. aeruginosa-pretreated
      rice plants challenged inoculation with R. solani (as pathogen), an additional
      increase in the accumulation of peroxidase was observed. Three pathogenesis
      related peroxidases in induced rice plants were detected; molar mass of these
      purified peroxidases was 28, 36 and 47 kDa. Purified peroxidase showed antifungal
      activity against phytopathogenic fungi R. solani, Pyricularia oryzae and
      Helminthosporium oryzae.

PMID- 17176756
TI  - Staphylococcus aureus biofilm as a target for single or repeated doses of
      oxacillin, vancomycin, linezolid and/or lysostaphin.
AB  - Due to high resistance, standard chemotherapy of biofilm-associated
      staphylococcal infections is ineffective and a number of alternative approaches
      to antimicrobial treatment have been proposed. Minimum inhibitory concentration
      (MIC) and biofilm inhibitory concentration (BIC) of oxacillin (Oxa), vancomycin
      (Van), linezolid (Lzd) and lysostaphin (Lss) as well as the possible synergistic
      effect of the antibiotics and lysostaphin were determined. The Lss susceptibility
      of Staphylococcus aureus planktonic and bio-film cultures varied and was strain
      dependent. The synergistic effect of sub-BIC(Lss)+Oxa was observed for
      methicillin-sensitive S. aureus (MSSa) and methicillin-resistant S. aureus
      (MrSa), but not for heterogeneously vancomycin-resistant S. aureus (V(h)Sa)
      biofilm. Van with sub-BICL(Lss) was effective against M(s)Sa and MrSa biofilm,
      when applied in three subsequent doses. Only sub-BICL(Lss)+Lzd combination, given
      as three cycles therapy, was effective in disruption of all 3 (M(s)Sa, M(r)Sa,
      V(h)Sa) biofilms.

PMID- 17176757
TI  - Incidence of lysogenic, colicinogenic and siderophore-producing strains among
      human non-pathogenic Escherichia coli.
AB  - The current incidence of Escherichia coli strains in healthy humans capable of
      producing the inhibitory exoproducts, such as temperate bacteriophages,
      corpuscular or HMW (high-molar mass) and proteinaceous or LMW (low-molar mass)
      colicins and siderophores was determined. Fifty-three E. coli strains were
      collected from the colons of 53 healthy human volunteers in Brno (Czechia) and
      tested for spontaneous and induced production of inhibitory exoproducts in a
      cross-test against each other. Of the strains tested, 37.7% produced
      bacteriophages, 41.5% produced from one to several LMW colicins, 11.3% formed HMW
      colicins and 15.1% (eight strains) produced exocellular siderophores different
      from enterochelin. Of these, seven strains formed aerobactin and one strain
      formed an untyped siderophore. E. coli strains differ greatly in the incidence of
      colicinogeny and lysogeny from its closest systemic relatives in the genus
      Escherichia and therefore should not be regarded as a model bacterium in this
      respect.

PMID- 17176758
TI  - Inhibition of mammalian cathepsins by Plesiomonas shigelloides.
AB  - To study molecular mechanisms underlying self-defense of the bacterial pathogen
      Plesiomonas shigelloides against host inflammatory and immune responses, we
      evaluated its interactions with mammalian papain-like cathepsins that are
      essential for host immunity. When grown under anaerobic, but not aerobic,
      conditions, P. shigelloides was shown to bind and inhibit papain, a model
      representative of the papain family of cysteine proteinases. This points to
      mammalian cathepsins as likely physiological targets of a novel cysteine
      proteinase inhibitor expressed on bacterial cell surface. Both papain and
      mammalian cathepsins L and B were inhibited by periplasmic extracts of
      aerobically and anaerobically grown bacteria, the inhibitory activity being
      higher in the latter. Inhibition by both intact cells and periplasmic samples was
      rapid and efficient. The results suggest a possible defensive role of bacterial
      inhibitors of cathepsins during invasion of a mammalian host. The bacteria thus
      may modulate host protective responses through inhibiting cathepsins involved in
      antigen processing and presentation.

PMID- 17176759
TI  - Improvement of enterocin P purification process.
AB  - Purification and heterologous expression of enterocin P (EntP), a sec-dependent
      bacteriocin produced by Enterococcus faecium, in Escherichia coli is described.
      PCR-amplified product of the enterocin P structural gene entP was cloned into
      plasmid pET-32b under the control of the inducible T7lac promoter. The neo
      synthesized EntP was genetically modified by an addition of 3 extra amino acids,
      leading to recombinant EntRP. Active EntRP was recovered from the cytoplasmic
      soluble fraction of E. coli harboring appropriate recombinant plasmid,
      characterized by ELISA and Western-blot analysis and purified by immunoaffinity
      chromatography. The use of E. coli as heterologous host and pET-32b as expressing
      vector offers promising tools for heterologous production of class IIa
      bacteriocin.

PMID- 17176760
TI  - The dose-dependent H2O2 stress response promotes increased survival for
      Schizosaccharomyces pombe cells expressing HIV-1 Vpr.
AB  - Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) exerts multiple
      effects on viral and host cellular activities during infection, including
      induction of the cell cycle G2 arrest, and cell death in both human cells and the
      fission yeast Schizosaccharomyces pombe. We show that treament of exponential
      phase wild-type Vpr-expressing S. pombe cells with a low, subinhibitory
      concentration (0.15 mmol/L) of hydrogen peroxide and 0.1 mmol/L thiamine
      significantly increased both cell proliferation and survival rates and decreased
      the number of elongated G2-arrested cells. Short-term, H2O2-induced adaptive
      stress increased the survival of the cells while acute stress conditions
      interrupted the Vpr-mediated death of the cells; however, no changes in cell
      length or cell phase were detected. The results suggest the importance of the
      oxidative status of the cells in Vpr-mediated processes. Our findings contribute
      to the development of a new approach via which to investigate the contribution of
      Vpr to HIV pathogenesis and to reduce the Vpr-mediated effects in HIV-infected
      patients.

PMID- 17176762
TI  - Biodegradation of synthetic polymers by composting and fungal treatment.
AB  - Two types of copolymers--poly(ester-amide)s--by the anionic copolymerization of
      epsilon-caprolactam and epsilon-caprolactone, and aromatic-aliphatic copolyesters
      based on glycolyzed polyethylene terephthalate from used beverage bottles and
      epsilon-caprolactone were prepared. Biodegradation tests of these copolymers were
      performed by two methods, viz. composting under controlled conditions and
      treatment with ligninolytic fungi. Both methods resulted in degradation of the
      copolymers, composting being more robust. Out of fungal strains tested Inonotus
      hispidus degraded aromatic-aliphatic copolyesters most intensively.

PMID- 17176764
TI  - Bacterial growth and community composition in fractions of dissolved organic
      carbon of different molar mass from interstitial water.
AB  - The ability of different molar-mass fractions of interstitial dissolved organic
      carbon (DOC) from a small stream to stimulate bacterial growth was determined.
      Growth was the greatest in the low-molar mass (<1 kDa) (LMM) fraction and the
      least in the high-molar mass (>10 kDa) (HMM) one. The LMM fraction consistently
      had a higher ratio of carbon to organic nitrogen than other fractions. The
      fluorescence in situ hybridization analysis revealed that bacterial populations
      in interstitial water were dominated by beta-Proteobacteria. gamma-Proteobacteria
      together with the Cytophaga-Flavobacteria cluster dominated in LMM DOC (66.3%)
      while the proportions of bacterial groups in HMM and medium-molar mass (MMM)
      fractions were more equal. The fact that gamma-Proteobacteria strongly dominates
      in LMM DOC fraction refutes the idea that LMM DOC is readily utilized by all
      heterotrophic bacteria.

PMID- 17176761
TI  - Exploration of yeast alkali metal cation/H+ antiporters: sequence and structure
      comparison.
AB  - The Saccharomyces cerevisiae genome contains three genes encoding alkali metal
      cation/H+ antiporters (Nha1p, Nhx1p, Kha1p) that differ in cell localization,
      substrate specificity and physiological function. Systematic genome sequencing of
      other yeast species revealed highly conserved homologous ORFs in all of them. We
      compared the yeast sequences both at DNA and protein levels. The subfamily of
      yeast endosomal/prevacuolar Nhx1 antiporters is closely related to mammalian
      plasma membrane NHE proteins and to both plasma membrane and vacuolar plant
      antiporters. The high sequence conservation within this subfamily of yeast
      antiporters suggests that Nhx1p is of great importance in cell physiology. Yeast
      Kha1 proteins probably belong to the same subfamily as bacterial antiporters,
      whereas Nhal proteins form a distinct subfamily.

PMID- 17176763
TI  - Structural and kinetic alterations of constitutive conidial alkaline phosphatase
      from the osmotically-sensitive mutant of Neurospora crassa.
AB  - The osmotically-sensitive os-1 mutant of Neurospora crassa overproduced conidial
      alkaline phosphatase. The enzyme was purified by Phenyl-Sepharose CL-4B
      chromatography and Sephadex G-200 gel filtration. PAGE analysis of the purified
      enzyme suggested the occurrence of aggregation and/or disaggregation phenomena.
      The enzyme is a glycoprotein containing 16% saccharide, with apparent molar mass
      of 137 kDa. Two protein bands (36 and 62 kDa) were observed in SDS-PAGE,
      suggesting that the native enzyme was a trimer. The pI was estimated to be 2.7,
      and optima of pH and temperature were 9.5 and 65 degrees C, respectively. The
      enzyme showed broad substrate specificity, hydrolyzing preferentially 4
      nitrophenyl phosphate, O-phosphoamino-acids and 2-phosphoglycerate. The
      hydrolysis of 4-nitrophenyl phosphate was stimulated by Co(II) (26%), Ni(II)
      (23%) and Mg(II) ions (80%). The enzyme was stable for up to 6 months at 4
      degrees C in 5 mmol/L Tris-HCl buffer and also upon storage at 25 degrees C for
      10 d. The kinetic and structural properties of the conidial enzyme purified from
      the os-1 mutant were quite different from those of the wild type strain. The
      enzyme overproduction observed in the mutant may be related to cell wall
      alterations that affect the process of enzyme secretion.

PMID- 17176765
TI  - Precipitation of minerals by 22 species of moderately halophilic bacteria in
      artificial marine salts media: influence of salt concentration.
AB  - Precipitation of minerals was shown by 22 species of moderately halophilic
      bacteria in both solid and liquid artificial marine salts media at different
      concentration and different Mg2+-to-Ca2+ ratio. Precipitation of minerals was
      observed for all the bacteria used. When salt concentration increased, the
      quantity and the size of bioliths decreased, the time required for precipitation
      being increased. The precipitated minerals were calcite, magnesian calcite,
      aragonite, dolomite, monohydrocalcite, hydromagnesite and struvite in variable
      proportions, depending on the bacterial species, the salinity and the physical
      state of the medium; the Mg content of the magnesian calcite also varied
      according to the same parameters. The precipitated minerals do not correspond
      exactly to those which could be precipitated inorganically according to the
      saturation indices. Scanning electron microscopy showed that the formation of the
      bioliths is initiated by grouping of calcified cells and that the dominant final
      morphologies were spherulitic with fibrous radiated interiors. It was
      demonstrated that moderately halophilic bacteria play an active role in the
      precipitation of carbonates and we hypothesize about this process of
      biomineralization.

PMID- 17176766
TI  - Development of alternative support system for viable count of cyanobacteria by
      most probable number method.
AB  - A technique was developed to evaluate alternative support systems to test tubes
      used in the standard most probable number technique, for simultaneous isolation
      and enumeration of cyanobacteria. Five different support systems were tested for
      their suitability in terms of accuracy, sensitivity, economics and ease of
      handling. PCR plates with 96 wells and carrying capacity of 300 microL per well
      were found to be most sensitive, besides being cost- and time-effective. This
      technique can also be useful for isolation of cyanobacteria, due to
      immobilization of colonies in the gel matrix and storage of samples at room
      temperature, without loss of viability for 5-6 weeks. This technique can help to
      process large sample size with ease--both for enumeration and isolation and can
      be extended for enumeration of other microorganisms from diverse sources.

PMID- 17176767
TI  - A new type of microscope illumination and its use in microbiology.
AB  - To overcome problems with taking photographs of motile microorganisms we used a
      new type of microscope illumination by means of a light-emitting diode (LED),
      which fully preserves the Kohler illumination principle. Oblique illumination or
      relief contrast after the Hostounsk, microscopy method were used for observing
      and photographing bacteria, flagellates and infusorians having different motion
      velocities with sufficient image contrast. The device, which permitted us to use
      short shutter time (1/30, 1/60 or 1/125 s), was successfully used in recording
      different motile microorganisms including their internal architecture.

PMID- 17176768
TI  - Differential methods of inoculation of plant growth-promoting rhizobacteria
      induce synthesis of phenylalanine ammonia-lyase and phenolic compounds
      differentially in chickpea.
AB  - Foliar spray and micro-injection of plant growth-promoting rhizobacterial
      species, viz. Pseudomonas fluorescens and P. aeruginosa on chickpea induced
      synthesis of phenylalanine ammonia-lyase (PAL) when tested against Sclerotinia
      sclerotiorum. Induction of PAL was also associated with increased synthesis of
      phenolic compounds such as tannic, gallic, caffeic, chlorogenic and cinnamic
      acids. Treatment with P. fluorescens was found to be more effective in inducing
      phenolic compounds as compared to P. aeruginosa. However, persistence of PAL
      activity was observed more with P. aeruginosa. Although both the inoculation
      methods were effective, foliar application was found to be superior to micro
      injection in terms of rapid PAL activity leading to the synthesis of phenolic
      compounds.

PMID- 17176769
TI  - Effects of murine endotoxemia on lymphocyte subsets and clearance of
      staphylococcal pulmonary infection.
AB  - In a model of staphylococcal pneumonia initiated during systemic endotoxemia in
      BALB/c mice, a significant reduction of the number of circulating CD4+ and CD8+ T
      lymphocytes, B-lymphocytes, and NK cells, as well as lung-resident total T- and
      CD4+ T-lymphocytes was demonstrated. Staphylococcus aureus exposure only induced
      a similar decrease of lymphocyte subsets in the blood. However, the number of
      lung-resident total T- and CD4+ T-lymphocytes was increased. More viable bacteria
      were recovered from the lungs of S. aureus-infected mice than from those animals
      previously treated with lipopolysaccharide (LPS) followed by a staphylococcal
      challenge. These results indicate that LPS-induced reduction in the number of
      circulating lymphocyte subsets and lung-resident total T- and CD4+ T-lymphocytes
      do not increase susceptibility to staphylococcal respiratory infection. Moreover,
      LPS challenge prior to S. aureus exposure significantly improves clearance of the
      bacteria in the lung.

PMID- 17176770
TI  - Establishment and follow-up of bifidobacterial species in the gut of healthy
      bottle-fed infants of 1-4 months age.
AB  - Twenty-one healthy bottle-fed infants were screened monthly (1-4 months) for
      bifidobacteria in their stools. Bifidobacteria were detected by culture and
      isolates specified by PCR. Alternatively, direct PCR in undiluted fecal
      suspensions was carried out for detection of bifidobacteria under the cultural
      detection level. All infants harbored cultivable bifidobacteria throughout the
      study period. Beerens medium was shown to permit a better recovery of
      bifidobacteria than MRS and horse blood Columbia agar. Direct PCR detection
      proved valuable in detecting species for which no cultural isolate could be
      recovered since the species were under the cultural detection level. B. bifidum,
      B. longum-infantis and B. breve were confirmed as dominant and stable species in
      infant stools while B. adolescentis and B. catenulatum group exhibited unstable
      colonization profiles. A trend towards B. breve decrease began at month 3 while
      carriage of the B. catenulatum group and B. adolescentis was rising. This
      observation warrants further analysis to assess a possible switch occurring at
      month 3 in bottle-fed infants, between so-called infant and adult bifidobacterial
      species.

PMID- 17176771
TI  - Oral administration of probiotic bacteria (E. coli Nissle, E. coli O83,
      Lactobacillus casei) influences the severity of dextran sodium sulfate-induced
      colitis in BALB/c mice.
AB  - Our study examined whether repeated preventive oral administration of live
      probiotic bacterial strains Escherichia coli O83:K24:H31 (Ec O83), Escherichia
      coli Nissle 1917 O6:K5:H1 (Ec Nis) and Lactobacillus casei DN 114001 (Lc) can
      protect mice against dextran sodium sulfate (DSS)-induced colitis. A significant
      decrease in average symptom score was observed in Ec O83-, Ec Nis- and Lc
      pretreated group (p < 0.05). Significant differences in body mass loss between Lc
      pretreated mice with DSS-induced colitis were found when compared with nontreated
      mice (p < 0.05). PBS pretreated mice had a significantly shorter colon than Ec
      O83-, Ec Nis- and Lc-pretreated mice (p < 0.05). Administration of Lc
      significantly decreased the severity of DSS induced histological marks of
      inflammation (p < 0.05). A significant difference (p < 0.05) was also found in
      specific IgA level against given probiotic in enteral fluid between colitic mice
      and healthy mice pretreated with Ec 083 and Ec Nis.

PMID- 17176772
TI  - Critical evaluation of the biological role of IgM in cerebrospinal fluid in
      inflammatory and other diseases of the nervous system.
AB  - In a group of 10,156 patients with neurological diseases, the IgM level was
      assessed (using laser nephelometry) both in cerebrospinal fluid (CSF) and serum;
      concentration of other 17 protein fractions was also simultaneously determined:
      albumin, immunoglobulins, acute phase reactants, complement components,
      apolipoproteins, proteinase inhibitors and alpha1-microglobulin. Total protein,
      element counts and glucose level were also evaluated. In patients with normal CSF
      findings, only limited statistically significant correlations were demonstrated
      between IgM and other CSF protein fractions while, in the group of patients with
      pathological CSF findings, significant correlations were found between CSF(IgM)
      and other immunoglobulins, complement fractions and the rate of intrathecal
      synthesis of immunoglobulins. Correlations were also found between CSF(IgM) and
      CSF antithrombin-III and alpha1-microglobulin. Correlations between CSF(IgM) and
      CSF apolipoproteins support the theory of CNS tissue destruction whenever the
      concentration of CSF apolipoproteins is elevated. Our data substantially
      contribute to establishing the diagnosis in patients with neurological diseases;
      simultaneous measurement of a high number of CSF proteins is becoming inevitable
      for a reasonable assessment of the CSF Protein Status.

PMID- 17176773
TI  - Recombinant single chain Fv antibodies specific for glycoprotein D of equid
      herpesvirus 1.
AB  - Single chain Fv (scFv) molecules generated by phage-display technology represent
      a new and efficient tool in the research and diagnostics of infectious diseases.
      The recombinant glycoprotein D of Equid herpesvirus 1 was successfully expressed
      in E. coli cells. The protein was produced predominantly in soluble fraction and
      was then purified on a nickel-agarose column. The scFv antibodies against the
      glycoprotein were selected and several clones of glycoprotein D-specific scFv
      antibodies were identified; t of them was expressed as a soluble scFv molecule,
      purified by immobilized metal-affinity chromatography and used as reagent in an
      immunofluorescence test.

PMID- 17176774
TI  - Changes in proliferation activity and relative distributions of lymphoid cell
      subpopulations in congenitally athymic nu/nu mice and Lurcher mice with
      spontaneous olivopontocerebellar degeneration.
AB  - Changes observed in mice with congenital damage of some part of the CNS
      neuroendocrine-immune regulatory system are described. nu/nu mice with congenital
      absence of thymus and Lurcher mice with spontaneous olivopontocerebellar
      degeneration displayed changes in the histoarchitecture of adrenal gland, immune
      organs (thymus, spleen, axillar lymph nodes) and intestine. Changes were also
      observed in IgM+, IgG+, CD4+ and CD8+ lymphoid cell subpopulations in the main
      lymphoid organs--the spleen and axillar lymph nodes and in the proliferative
      ability of whole lymphoid cell populations. The extreme decrease of lymphoid T
      cell subpopulations in athymic nu/nu mice is the consequence of the absence of
      thymus, the organ of their maturation. On the other hand, a relative increase of
      B-cell subpopulations was found in this mouse strain. A relative decrease of CD4+
      lymphocytes and a different influence of immunization on B-cell subpopulations
      were found in the spleen in neurodeficient Lurcher mice. The high percentage of
      apoptotic cells, cells in the S-phase of cell cycle and increased proliferation
      index in nu/nu mice suggest that the turnover and renewal of lymphoid cells in
      the spleen in nu/nu mice is more rapid than in control immunocompetent BALB/c
      mice.

PMID- 17176776
TI  - What drives the inflammatory response in rhinosinusitis.
AB  - The dilemma of treating chronic sinusitis continues to confuse clinicians. When
      mucosal thickening does not respond to aggressive antibiotic therapy, other
      etiologies should be considered. Perhaps the most likely is the inflammatory
      response. In comparison with asthma, chronic sinusitis exhibits amazing
      similarities. Atopic dermatitis also exhibits similar inflammatory responses that
      lead to thickening of the skin in a manner not dissimilar to mucosal thickening.
      The interactions amid eosinophils, lymphocytes, leukotrienes, interleukins, and
      epithelial cells serve as a reminder that there is one immune response and
      similarities exist in the pathophysiology of these conditions.

PMID- 17176775
TI  - Probiotics manipulate host cytokine response and induce antimicrobial peptides.
AB  - Probiotics modulate production of both cytokine and antimicrobial peptides. This
      effect can be regarded as a part of complex interplay between them and the host.

PMID- 17176778
TI  - Immune dysregulation in atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic, inflammatory
      skin disease characterized by cutaneous hyperreactivity to environmentals
      triggers. Recent data suggest the presence of two different forms of AD: an
      extrinsic AD with elevated IgE involving 70-80% of the patients and an intrinsic
      AD with serum IgE not elevated and no specific IgE. Patients with extrinsic AD
      have elevated Th2- and decreased Thl-expressing cells in the peripheral blood,
      with elevated IL-4 and IL-13 expression, as well as IL-5. On the contrary, the
      intrinsic AD is linked with much lower levels of IL-4 and IL-13. Genetic factors
      are involved in the control of the disease and in the intrinsic AD the same
      chromosomal regions seem to be associated with psoriasis susceptibility. The AD
      is characterized by a complex of immunological alterations involving interactions
      between IgE-bearing antigen-presenting cells, T-cell activation, mast-cell
      degranulation, keratinocytes, eosinophils, and a combination of immediate and
      cellular immune responses. Inflammatory dendritic epidermal cells constitute a
      distinct dendritic cells population that is mainly found in AD and could induce
      the Th2/Thl isotopic switch contributing to AD chronic phase. Therapy is based on
      interventation in the pathophysiology of atopic eczema and elimination of
      exogenous provocation factors.

PMID- 17176777
TI  - Sinusitis: viral, bacterial, or fungal and what is the role of Staph?
AB  - Recently, it has been recognized that inflammation is the major cause of chronic
      rhinosinusitis (CRS) rather than bacterial infection. Fungi have emerged as a
      possible pathogenic agent that drives CRS. One clear-cut group of fungal
      sinusitis can be divided into invasive and noninvasive. The condition that the
      allergist is most likely to see is allergic fungal sinusitis. Generally, it
      appears in atopic, immunocompetent, adolescents and young adults and is marked by
      the presence of nasal polyps and allergic mucin, which includes eosinophils,
      Charcot-Leyden crystals, and fungal hyphae. Computer tomographic imaging shows
      sinus opacification with hyperdense areas. Treatment has been successful with
      definitive nasosinus surgery and long-term oral prednisone. There is some
      evidence that fungi also may account for a large percentage of the remaining CRS
      patients. In this instance, the immune response to common airborne fungi appears
      to be IgG mediated rather than IgE mediated. Promising therapeutic results have
      been seen with intranasal antifungal agents but larger multicenter double-blinded
      placebo-controlled studies are needed. Another unanswered question includes the
      possible role of staphylococcus-derived enterotoxins in the pathogenesis of CRS.

PMID- 17176779
TI  - Immunization update and hot topics in clinical immunology: how does this relate
      to my practice?
AB  - The prevention of infectious diseases by the use of vaccines represents one of
      medicine's greatest triumphs during the 20th century. This era has witnessed the
      global eradication of smallpox as a result of Jennerian cowpox vaccination, the
      elimination of paralytic poliomyelitis from the western hemisphere, and within 5
      10 years the anticipated eradication of poliomyelitis worldwide as a result of
      the poliovirus vaccines. Next slated for worldwide eradication is measles, the
      great killer of infants and children, which each year extracts a global mortality
      of one million victims. Throughout the 20th century the percutaneous (i.e.,
      subcutaneous or intramuscular) route has almost exclusively been the preferred
      way to administer vaccines. However, as a result of several important scientific
      discoveries made during the 20th century, including new tissue-culturing
      techniques, the development of recombinant DNA technology, and genetic
      sequencing, a whole new generation of tailor-made modern vaccines has become
      available, including DNA vaccines and transgenic plant vaccines. Moreover, it
      became apparent that alternative routes of administration of vaccines, such as by
      aerosol immunization might be more appropriate and more effective than
      immunization via the parenteral route. The overall success in vaccine
      development, however, has not been without cost. For every new vaccine that has
      been developed, an adverse effect has been seen. Thus, although modern vaccines
      are extremely safe and effective, they are neither completely safe nor completely
      effective. The goal of vaccine development, therefore, is to achieve the highest
      degree of protection and the lowest rate of adverse effects. This paper describes
      some of the recent advances in vaccine development and will focus on some hot
      topics relating to the recent development and use of respiratory aerosolized
      vaccines.

PMID- 17176780
TI  - Effect of desloratadine on the control of morning symptoms in patients with
      seasonal and perennial allergic rhinitis.
AB  - The symptoms of allergic rhinitis vary in severity over the course of the day and
      often are worse in the morning. This review focuses on data from clinical studies
      of the antihistamine desloratadine to establish whether it effectively controls
      the morning symptoms of allergic rhinitis. Studies of desloratadine in patients
      with allergic rhinitis that used instantaneous scoring to assess the severity of
      morning symptoms were selected for inclusion from published literature (peer
      reviewed articles and abstracts presented at professional meetings). When
      administered once daily, desloratadine is effective in alleviating the morning
      symptoms of allergic rhinitis, including nasal congestion. Its action is
      sustained over the 24-hour dosing interval. A comparison of morning and evening
      dosing of desloratadine revealed equivalent relief of morning symptoms,
      illustrating that the effect of desloratadine is independent of the time of
      dosing. Clinical studies indicate that desloratadine is nonsedating and well
      tolerated, with no evidence of adverse cardiac effects. For many patients with
      allergic rhinitis, symptoms are most severe in the morning. To maximize the
      benefits for patients, pharmacologic agents used in the management of allergic
      rhinitis should be effective in controlling these peak morning symptoms. The
      sustained 24-hour action of desloratadine and its effective control of morning
      symptoms make it a valuable tool for improving the quality of life of patients
      with allergic rhinitis.

PMID- 17176781
TI  - A comparison of two single-headed and two multi-headed allergen skin test
      devices.
AB  - Given the potential differences in performance of skin test devices, the purpose
      of this study was to prospectively assess the performance of two single-headed
      and two multiheaded devices for allergy skin testing in terms of wheal size,
      sensitivity, specificity, intradevice variability, and pain level. Two single
      headed devices (Greer Pick, Duotip-Test) and two multiheaded devices (Multi-Test
      II, OMNI) were tested in 15 subjects in a prospective partially blind fashion
      looking at wheal reactions and pain using histamine and glycerol-saline on the
      arms and back. Differences among devices in wheal size and pain were noted.
      Sensitivity, specificity, and intradevice variability were calculated.
      Differences between corner and interior heads in multiheaded devices were
      analyzed. No significant differences were observed in wheal size between Greer
      Pick (7.1+/-1.4 mm) and Duotip-Test (7.2+/-1.6 mm). Multiheaded devices were
      significantly different in wheal size compared with each other and to the single
      headed devices (Multi-Test II, 5.4+/-1.7 mm; OMNI, 3.3+/-1.2 mm). Single-headed
      devices were more sensitive (100% each, 95% CI of 92-100%) than the multiheaded
      devices. Multi-Test II was significantly more sensitive (83%, 95% CI of 78-87%)
      than OMNI (57%, 95% CI of 51-62%). There was significant intradevice variability
      for the multiheaded devices with corner heads being significantly more sensitive
      than interior heads. Specificities for all devices were equally good (-97%). Pain
      was greater for multiheaded devices than single-headed devices but was generally
      mild. In conclusion, this study supports the idea that single-headed devices may
      be more sensitive and consistent than multiheaded devices. Multi-Test II is more
      sensitive than OMNI. In multiheaded devices, corner heads are more sensitive than
      interior heads.

PMID- 17176782
TI  - Longitudinal changes of pulmonary function and bronchial responsiveness in cough
      variant asthma treated with bronchodilators alone.
AB  - Cough due to cough-variant asthma (CVA) responds well to bronchodilators such as
      beta 2 adrenergic agonists. The aim of this study was to assess longitudinal
      changes of pulmonary function and bronchial responsiveness in CVA, which was
      treated with bronchodilators alone. Seventeen CVA patients recorded intensity and
      frequency of cough every day. Spirometry and provocative concentration of
      methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20)
      were measured in the run-in period and after cough almost completely relieved on
      therapy. Cough score had improved within 2 weeks after the initiation of
      bronchodilator therapy. Forced expiratory volume in one second (FEV1) was
      significantly increased from 2.7 +/-0.7 L in the run-in period to 2.8+/-0.7 L
      after improvement of cough. However, the geometric mean (GSEM) PC20 value did not
      change from the run-in period [1542 (GSEM 1.29) microg/mL] to the time of
      improvement [2600 (GSEM 1.43) microg/mL]. Mildly increased bronchial
      responsiveness in CVA does not improve when only bronchodilator therapy is
      carried out. Because bronchial hyperresponsiveness has been shown to be a risk
      factor for typical asthma onset from CVA, the effect of inhaled corticosteroids
      on the longitudinal changes in bronchial responsiveness should be examined.

PMID- 17176783
TI  - Real-world assessment of a metered-dose inhaler with integrated dose counter.
AB  - Currently available metered dose inhalers (MDIs) do not track the remaining
      number of doses, indicating the need for a device that accurately monitors
      medication use. In an open-label study at 37 outpatient centers, patients > or =4
      years old with asthma or chronic obstructive pulmonary disease requiring short
      acting 32-agonists received two actuations of albuterol hydrofluoroalkane (HFA)
      [Ventolin HFA: GlaxoSmithKline], 90 microg twice daily, via a novel MDI with an
      integrated dose counter until all 200 actuations were completed. Concordance
      between counter readings, diary card-recorded actuations, and canister weights
      were measured in patients who completed > or =90% of the labeled actuations (n =
      224). Adverse events and patient satisfaction were assessed in the intent-to
      treat population (n = 268). In 43,865 recorded actuations, 333 counter versus
      diary discrepancies occurred (discrepancy rate of 0.76%), and 88% of
      discrepancies were by one to two actuations. Forty-seven percent of patients had
      no discrepancies. Incidence of the device firing without changes in counter
      readings was very low (0.09%). Mean expected actuations based on canister weights
      (184) were slightly lower than mean counter and diary-reported actuations (200
      each). At baseline, 62% of patients reported anxiety about not knowing the
      quantity of medication remaining in their inhaler. On study completion, 92%
      expressed satisfaction with the dose counter and 92% agreed it would help prevent
      them from running out of medication. The adverse event profile showed that
      albuterol HFA was well tolerated. Integrated MDI counters are a useful and
      reliable tool for tracking a patient's medication supply.

PMID- 17176784
TI  - Exhaled nitric oxide levels in military recruits with new onset asthma.
AB  - Approximately 800 United States Air Force basic military trainees (BMTs) are
      diagnosed with asthma, annually, resulting in separation from the military. With
      training costs of approximately 10,000 dollars/person, around 8 million dollarsis
      lost per year. Improved methods in diagnosing asthma would be beneficial. The aim
      of this study was to determine the fraction of exhaled nitric oxide (FENO), a
      marker of airway inflammation, in a military recruit population referred for an
      asthma evaluation. In BMTs referred for respiratory complaints during basic
      training, FENO levels were determined before an asthma evaluation consisting of a
      history, physical, baseline spirometry, and histamine bronchoprovocation. Of 172
      BMTs who had symptoms suggestive of asthma and underwent histamine
      bronchoprovocation, 80% were diagnosed with asthma. FENO levels were
      significantly higher in asthmatic patients than nonasthmatic patients (mean, 30
      parts per billion [ppb] versus 19 ppb, p < 0.001; median, 21 ppb versus 17 ppb, p
      < 0.02). Various FENO cutoff points provided a range of sensitivity and
      specificity for the diagnosis of asthma. However, an optimal FENO cutoff level
      for asthma was not obtained. An FENO value of 10.5 ppb provided a sensitivity of
      86% for the diagnosis of asthma, but specificity was only 21%. In contrast, an
      FENO value of 46 ppb provided 100% specificity but only 17% sensitivity. FENO
      levels were significantly elevated in BMTs diagnosed with asthma but the lack of
      an optimal cutoff level limits the test as a diagnostic tool for asthma.
      Additional studies are necessary to determine the value of FENO for asthma
      screening in a military population.

PMID- 17176785
TI  - Effect of body mass index on quality of life in allergic/asthmatic patients.
AB  - Evaluation of quality of life (QoL) is of particular interest in patients
      suffering from chronic diseases. Although studies have shown an association
      between QoL and obesity and allergy/asthma, the effect of obesity on QoL is not
      well known. The aim of this study was to assess the impact of body mass index
      (BMI) as a contributory factor on QoL in patients with a diagnostic label of
      allergy/asthma. We surveyed 100 patients (69 F/31 M) (age 34.15+/-13.32 years),
      and 65 healthy controls (42 F/23 M) (age 35.45 +/-8.96 years). QoL was determined
      by SF-36. BMI > or = 25 kg/m(2) was accepted as overweight/obesity. Forty-five
      percent of the patients had BMI > or = 25 kg/m(2) with no difference between the
      genders. They were significantly older and more likely to have less education
      level than those with BMI < 25 kg/m(2). Quality-of-life scores among patients
      with allergy/asthma were lower than those in the control group, irrespective of
      BMI. However, increased BMI was found to be related with improved quality of life
      among controls. Pearson's analysis showed that BMI was inversely correlated with
      physical functioning among patients (r = -0.229, p = 0.034), but in the control
      group it was positively correlated with QoL. All the domains of SF-36, except
      role-physical ones, among female subjects were significantly impaired more than
      those of male patients. It has been shown that the major determinants of impaired
      QoL are female sex, older age, and less educational status in patients with
      allergic/asthmatic symptoms. The impact of BMI on QoL could be undermined,
      because it seems to play a minor role.

PMID- 17176786
TI  - Computed tomography evaluation of paranasal sinuses in asthma: is there a
      tendency of particular site involvement?
AB  - Although the precise mechanism is unclear, asthma and chronic sinusitis are
      associated frequently. Computed tomography (CT) is a sensitive modality for
      documenting sinonasal mucosal abnormalities. The aim of this study was to
      evaluate paranasal mucosal abnormalities in asthma and whether there was a
      relationship with asthma severity. One hundred fifty-five patients with asthma
      and 36 normal control subjects were assessed with coronal sinus CT. Asthma was
      classified as mild, moderate, or severe. Scoring of paranasal sinus abnormalities
      were assessed for total sinus, total mucosal, and individual sites. The mean
      scores of total mucosal changes (8.45 points versus 4.67 points, p < 0.001) and
      total sinus scores (5.50 versus 2.69, p < 0.005) were significantly higher in the
      asthmatic patients compared with controls. Nasal passage and frontal sinus
      involvements were not statistically different between groups, but all other
      individual scores were significantly higher in asthmatic patients. There was an
      involvement site tendency with respect to increasing severity of asthma. Mean
      total mucosal CT scores (12.57 points versus 7.33 points, p < 0.05) and
      individual site scores were statistically higher in asthmatic patients with high
      blood eosinophil levels compared with those patients with normal blood eosinophil
      counts except for nasal passage disease. There was no significant relationship
      between total IgE level and CT scores. Total mucosal and sinus scores were
      significantly related with asthma severity. There was an involvement tendency of
      sinuses and sites. Nasal passage involvement was unrelated with asthma. Ethmoidal
      sinuses and ostiomeatal complexes were involved significantly in patients with
      mild asthma, whereas maxillary, frontal, and sphenoidal sinuses were involved
      significantly in patients with severe asthma.

PMID- 17176787
TI  - Clinical aspects of the link between chronic sinonasal diseases and asthma.
AB  - Chronic sinonasal diseases (CSDs) are common comorbidity of asthma. The aim of
      this study was to assess comprehensively CSD in a population of asthma patients
      and determine whether the clinical factors in both diseases were related to each
      other. Eighty adult stable asthmatic patients with sinonasal symptoms (SNSs) of 3
      months and who were nonresponsive to aggressive medical treatment were
      prospectively investigated. All patients underwent a detailed ear, nose, and
      throat examination and were evaluated by paranasal sinus computed tomography (PNS
      CT). The severity of asthma was compared with SNS scores (SNSSs) and sinonasal
      involvement on PNS-CT. Asthma was severe in 12.5%, moderate in 55%, and mild in
      32.5% of cases. There were 15 (18.7%) patients in stage 0, 16 (20%) patients in
      stage 1, 21 (26.2%) patients in stage 2, and 28 (35%) patients in stage 3
      according to PNS-CT scoring. There was no correlation between asthma severity and
      CT stages, total opacification scores (TOSs), anatomic variations, and SNSSs.
      Although SNSSs were similar in patients with nasal polyps (NPs) and without NPs,
      patients with NPs showed significantly higher TOSs and CT stages (p < 0.05). The
      presence of NPs and age and duration of disease were related to severity of
      asthma (p < 0.05). Nonatopic asthmatic patients had both more severe asthma (p =
      0.05) and more extensive CT findings (p = 0.01). The use of clinical symptoms
      alone is not very reliable in predicting the presence or severity of CSD.
      Therefore, SNSs should be supported with objective criteria such as nasal
      endoscopy and PNS-CT scan. Furthermore, sinonasal involvement may exist
      independently from severity of asthma.

PMID- 17176788
TI  - Production of interferon gamma in asthmatic patients with small bacille Calmette
      Guerin scars: a pilot study.
AB  - Some studies suggest a decrease in interferon (IFN) gamma production among atopic
      individuals, and others refer to low IFN-gamma levels as a characteristic of
      asthma, regardless of the atopic state. Recent research has indicated a relation
      between asthma and a tendency toward a bacille Calmette-Guerin (BCG) vaccine scar
      with a small diameter, suggesting an association of this illness with the low
      production of IFN-gamma. The aim of this study was to check the hypothesis that
      asthmatic patients with a small BCG scar present low IFN-gamma production. This
      work was a quasi-experimental study. The capacity to produce IFN-gamma among 12
      asthmatic patients with an average BCG vaccine scar diameter <5 mm was compared
      with 7 nonasthmatic individuals with scars > or =5 mm using whole blood cells
      stimulated by purified protein derivative (PPD), phorbol myristate
      acetatelionomycin (PMA/Iono) and medium (no stimulus). The study also analyzed
      the relation between IFN-gamma production after PPD stimulation and eosinophil
      count, total IgE, and dust-mite-specific IgE levels. The asthmatic patients
      presented a decrease in IFN-gamma production in comparison with a control group
      after PPD stimulation (p < 0.02). However, the same was not observed when
      PMA/Iono stimulation was used or when no stimulation was used. Asthmatic patients
      with small BCG scars showed a decrease in IFN-gamma production, suggesting that
      there may be an intrinsic characteristic of these patients.

PMID- 17176789
TI  - Efficacy and safety of tacrolimus ointment 0.03% treatment in a 1-month-old "red
      baby": a case report.
AB  - Several trials have indicated that topical tacrolimus is safe and effective for
      several immunologic-based skin disorders. We report a child <2 months old, who
      was admitted to our pediatric department because of generalized erythroderma. We
      started tacrolimus ointment 0.03% therapy by applying the ointment to the skin
      once daily, on a limited surface of 10 cm(2), changing the skin areas only after
      the disappearance of inflammation. After only one application we observed a
      marked improvement of the treated area and after another application the
      localized erythroderma disappeared. We changed the site of application and
      continued this treatment regime for 4 weeks. After 2 weeks we reduced treatment
      application once every other day and after an additional 2 weeks we discontinued
      therapy because of complete resolution of erythroderma. No adverse clinical
      effect was recorded and tolerance to the treatment was good. We conclude that
      0.03% tacrolimus ointment is efficacious and safe even in an infant <2 months of
      age.

PMID- 17176790
TI  - Tacrolimus ointment in nickel sulphate-induced steroid-resistant allergic contact
      dermatitis.
AB  - Tacrolimus ointment is a topical immunomodulator. Currently, there is available
      evidence regarding the potential use of topical tacrolimus in a range of
      dermatological disorders. The aim of this study was to evaluate the efficacy and
      safety of tacrolimus ointment 0.1% for the nickel sulfate-induced steroid
      resistant allergic contact dermatitis (ACD). A randomized, double-blind, placebo
      controlled, parallel-group study design was performed in a total of 28 patients
      affected by nickel sulfate-induced steroid-resistant ACD after a 14-day run-in
      period. Then, the enrolled patients were randomized into two subgroups. Group A
      was treated with tacrolimus for 14 days and finally observed for a 7-day follow
      up period. Group B, instead, was treated with placebo (vehicle). Four major
      symptoms (erythema, oozing, scaling, and itching) were considered as outcomes
      during the different phases of the study. In group A, during the treatment period
      with tacrolimus, a significant improvement was observed in all four considered
      symptoms. On the other hand, no improvement in symptoms was observed in the
      placebo-treated group B. Local adverse events in the tacrolimus-treated group,
      such as burning/itching at the application site, were transient and well
      tolerated. No patients withdrew because of burning/itching. In our study,
      tacrolimus ointment 0.1% appeared to be both effective and safe in the treatment
      of nickel sulfate-induced steroid-resistant ACD.

PMID- 17176791
TI  - Intrainfusion and postinfusion adverse events related to intravenous
      immunoglobulin therapy in immunodeficiency states.
AB  - The i.v. immunoglobulin (IVIG) therapy is one of the mainstays of treatment for
      humoral immunodeficiencies, but there is limited knowledge of the adverse
      reactions associated with this therapy, especially reactions occurring in the
      postinfusion period. The purpose of this prospective, observational, multicenter
      study was to identify and quantify the adverse reactions that can occur both
      during and after IVIG infusions (Gamimune N) in patients with humoral
      immunodeficiency. Patients with primary immunodeficiencies requiring IVIG therapy
      were followed over a 6-month period, and data regarding adverse events,
      particularly the time of onset, duration, and type of reaction associated with
      IVIG infusions wzas collected via direct observation and patient interviews. Data
      were obtained during and up to 72 hours after the completion of infusions. Sixty
      five patients were recruited and received a total of 447 infusions over a 6-month
      period. Four hundred fifty-one adverse reactions were noted, with 17% of
      infusions associated with an intrainfusion reaction and 41% associated with a
      postinfusion reaction. Most postinfusion reactions occurred within 24 hours of
      the infusion and consisted mainly of headaches, fatigue, and nausea. Adverse
      reactions to Gamimune N infusions are common and occur primarily in the
      postinfusion period. Estimates of the rate of adverse reactions to Gamimune N
      infusions currently are underestimated because they do not account for
      postinfusion reactions. In addition, once recognized, effective treatment of
      postinfusion reactions may improve patient compliance and quality of life.

PMID- 17176792
TI  - Necrotizing enterocolitis in an infant with Omenn syndrome.
AB  - Omenn syndrome (OS) is a rare disorder within the combined immunodeficiency
      family that is characterized by a diffuse exudative, erythematous rash,
      lymphadenopathy, hepatosplenomegaly, alopecia, and failure to thrive. Specific
      lab findings unique to OS include hypereosinophilia, elevated IgE, excess
      production of oligoclonal T-cells and near-to-absent B-cells. Much remains
      elucidated about the underlying genetic cause of OS. Until recently, it was felt
      that the disease was primarily caused by mutations of the RAG1 or RAG2 genes. The
      type of mutation of the RAG1 and RAG2 genes in patients with OS affects the
      degree of functioning variable (diversity) joining [V(D)J] recombination
      activity, which is critical to the development of lymphoid cell receptor
      diversity. New work has also shown that thymic tissue in OS patients demonstrates
      a severe defect in the expression of the autoimmune regulator element. This may
      contribute to the development of autoreactive T-cells that are felt to be the
      causative agent of a number of the clinical hallmarks unique to OS. The genetic
      spectrum of OS was further expanded when a patient with clinical and immunologic
      features consistent with OS, without RAG mutation, was found to have mutations in
      both alleles coding for ARTEMIS, a key V(D)J recombination/DNA repair factor.
      Regardless of the underlying cause, early recognition is critical because
      patients die at a very young age without bone marrow transplantation. We describe
      an infant diagnosed with OS post-mortem in which death was directly related to
      the development of necrotizing enterocolitis.

PMID- 17176793
TI  - Serratia marcescens osteomyelitis in an infant.
AB  - Neutrophil dysfunction can result from oxidative burst defect or from glucose-6
      phosphate dehydrogenase (G6PD) deficiency; we noted both in the same patient. A 4
      month-old male infant with G6PD deficiency presented with swelling of the left
      middle finger, left leg, and right big toe. At 5 weeks of age he was hospitalized
      for fever for 2 days. A maternal uncle died at 5 years of age and a male maternal
      cousin died at the age of 21 months, both reportedly diagnosed with chronic
      granulomatous disease (CGD). On physical examination, he had a swollen
      erythematous left third finger, left distal leg swelling, and right big toe
      abscess. None of these areas was significantly tender. WBC was 18.7 x 10(3)/mm(3)
      with 37% PMN and 5% bands. The x-ray films showed osteomyelitis in the left third
      proximal phalanx and the distal right first metatarsal. Culture from the toe
      abscess grew Serratia marcescens. His neutrophil oxidative burst was tested by
      the dihydrorhodamine-123 assay and was markedly suppressed, typical of CGD. The
      mother and maternal grandmother were found to be CGD carriers. He was treated
      with i.v. antibiotics for 4 weeks and was discharged on prophylactic
      trimethoprim, itraconazole and interferon gamma, with substantial reduction in
      infections. Infection in this infant was unusual in its nature, in affecting
      multiple sites, and in its causative organism. Immune deficiency was suspected,
      particularly of the phagocytic component, but could not be attributed to his
      moderate degree of primary G6PD deficiency. Additional immunologic evaluation and
      the family history led to the diagnosis of X-linked CGD.

PMID- 17176794
TI  - Quality of life in patients undergoing thyroid surgery.
AB  - OBJECTIVE: The extent of thyroidectomy in the management of low-risk, well
      differentiated thyroid carcinoma (WDTC) has been debated extensively. Our
      objective was to determine if hemithyroidectomy has a less detrimental effect on
      quality of life (QOL) than total thyroidectomy. DESIGN: Prospective, nonblinded,
      nonrandomized, cohort study. SETTING: Tertiary care academic otolaryngology-head
      and neck surgery practice. METHODS: Using both disease-specific and global QOL
      instruments, patients treated with either hemi- or total thyroidectomy were
      prospectively followed. QOL was assessed preoperatively and for 12 months
      postoperatively. MAIN OUTCOME MEASURES: Scores on the two QOL instruments
      throughout a 12-month postoperative period. RESULTS: Patients with cancer
      experienced a greater drop in QOL during the first 6 months following surgery
      when compared with patients with benign disease (p < .03). Additionally, patients
      treated with total thyroidectomy did not have a significantly different QOL than
      patients treated with hemithyroidectomy (p > .2). CONCLUSION: These results
      suggest that QOL is not significantly impacted by the extent of surgery and that
      QOL should not be a factor in the decision-making process for the treatment of
      low-risk WDTC.

PMID- 17176795
TI  - 3-year impact of a provincial choking prevention program.
AB  - OBJECTIVE: To determine the impact of a provincial choking prevention program
      (CPP) on the incidence of aerodigestive foreign body cases among children.
      METHODS: The CPP, including posters, pamphlets, an informative video, and annual
      participation in the Parents & Kids Fair, was launched throughout Quebec in
      October 1999. The incidence rates of aerodigestive foreign body cases prior to
      implementation (during 1997-1998) and subsequently (2000-2002) within the
      province and our tertiary care centre (Sainte-Justine Hospital) were compared by
      estimating incidence rate ratios (IRRs) and associated 95% confidence intervals
      (95% CIs). RESULTS: No significant changes in the incidence of aerodigestive
      foreign body cases after program implementation were observed in our hospital
      (age-adjusted IRR 0.92, 95% CI 0.79-1.07). The provincial rates were higher after
      program implementation (age-adjusted IRR 1.15, 95% CI 1.05-1.25). CONCLUSIONS: To
      influence choking prevention habits, modifications to the campaign are required.
      Strategies are discussed.

PMID- 17176796
TI  - Why do some children have good hearing results following type III and IV
      tympanoplasty? Current theories of middle ear mechanics.
AB  - INTRODUCTION: Middle ear reconstruction in children following
      tympanomastoidectomy for cholesteatoma is commonly limited to a Wullstein type
      III or IV reconstruction owing to ossicular erosion. The hearing outcomes of this
      procedure have been unpredictable. Nevertheless, there are children who have
      remarkably good hearing results despite having extensive and aggressive
      cholesteatoma surgery and limited reconstruction. METHODS: The current theories
      of middle ear mechanics following tympanoplasty and ossicular reconstruction are
      reviewed. In addition, a selective retrospective chart review of pediatric type
      III and IV tympanoplasty at The Hospital for Sick Children between 1998 and 2003
      is presented. RESULTS: Nine patients were reconstructed with a type III (n = 3)
      or IV (n = 6) tympanoplasty. The mean pre- and postoperative air-bone gaps were
      43.6 and 24.9 dB. Speech reception threshold improved from 37.5 to 22.8 dB. The
      changes were statistically significant (p < .05). CONCLUSIONS: This series of
      patients demonstrated a statistically significant hearing improvement at long
      term follow-up. The improvements are consistent with optimal hearing outcomes
      predicted by current theories of middle ear mechanics.

PMID- 17176797
TI  - Primary radiotherapy for tonsillar carcinoma: a good alternative to a surgical
      approach.
AB  - OBJECTIVES: To review the Notre-Dame hospital experience in the treatment of
      tonsillar carcinoma with primary radiotherapy and to evaluate the different
      factors affecting locoregional control (LRC) and survival. METHODS: We reviewed
      the records of 164 patients treated consecutively for squamous cell carcinoma of
      the tonsillar region between January 1990 and June 1999. Our study included 22
      T1, 75 T2, 54 T3, and 12 T4 lesions; according to N stage, there were 48 N0, 50
      N1, 51 N2, and 15 N3 disease. Overall staging was 6 stage I, 28 stage II, 62
      stage III, and 67 stage IV disease. All patients received curative radiotherapy,
      and 31 patients received chemotherapy either prior to or during treatment with
      radiotherapy. No patient received surgery as a primary treatment modality.
      RESULTS: The median follow-up was 4.2 years for all patients and 5.4 years for
      alive patients. The overall LRC rate was 72% at 5 years. By T and N stage, local
      and regional control rates at 5 years were as follows: T1, 82%; T2, 74%; T3, 66%;
      T4, 65%; N0, 77%; N1, 83%; N2, 65%; and N3, 38%. Significant favourable
      prognostic factors for LRC on univariate analysis were N stage and global stage.
      On multivariate analysis, the single favourable prognostic factor was N stage.
      The overall survival (OS) rate was 57% at 5 years. By T and N stage, OS at 5
      years was as follows: T1, 62%; T2, 67%; T3, 45%; T4, 22%; N0, 63%; N1, 70%; N2,
      46%; and N3, 32%. Significant prognostic factors for OS on univariate analysis
      were T stage, N stage, and global stage. Favourable prognostic factors for OS on
      multivariate analysis were T stage and N stage. CONCLUSION: Lower N stage was a
      favourable prognostic factor for LRC and OS, whereas lower T stage was a
      favourable prognostic factor on OS. Our results compare favourably with other
      single-institution surgical series and justify the role of radiotherapy as a
      primary treatment modality in early tonsillar carcinoma. Concurrent chemotherapy
      and radiation therapy is currently our standard of care in advanced tonsillar
      carcinoma.

PMID- 17176798
TI  - Factors affecting unanticipated hospital admission following otolaryngologic day
      surgery.
AB  - BACKGROUND: Day surgery constitutes an important part of modern otolaryngology
      practice. However, high rates of unplanned admissions remain an issue. OBJECTIVE:
      To determine the incidence, reasons, and predictive factors for unanticipated
      admission after ambulatory otolaryngologic surgery. METHODS: A retrospective
      review of all cases of unplanned admission following otolaryngology day surgery
      at a tertiary care centre over a 4-year period from 2000 to 2004. Data relating
      to patient demographics, physical status, surgical procedure, perioperative
      complications, and reasons for hospital admission were recorded. A case-control
      analysis of these parameters with nonadmitted day surgery patients was used for
      comparison. RESULTS: During the above period, 1106 patients underwent
      otolaryngologic day surgery, of whom 74 (6.7%) required admission. Fifty-seven
      percent of the patients were male, and the average age was 48.9 years. The three
      most common procedures with unplanned admission were open neck biopsy (27%),
      functional endoscopic sinus surgery (20.3%), and panendoscopy (16.2%). The
      reasons for admission could be divided into airway monitoring (37.7%),
      postoperative bleeding (28.6%), the need for supportive or pain management
      (19.5%), anesthetic complication (5.2%), cardiovascular complication (3.9%),
      clerical error (3.9%), and suspicion of a cerebrospinal fluid leak (1.3%). Risk
      factors for admission were determined to be an American Society of
      Anesthesiologists' class of 3 or greater, open neck surgical procedures, and a
      length of surgery of 60 minutes or greater. Minor factors included the use of
      general anesthesia, male gender, advanced age, and living far from a hospital.
      CONCLUSIONS: This study suggests strategies to reduce the rate of unplanned
      admission by means of careful preoperative assessment and planning, patient
      selection, careful scheduling of higher-risk patients, and appropriate
      postoperative observation and management.

PMID- 17176799
TI  - Orbital decompression: cadaver study.
AB  - BACKGROUND: Patients with Graves' ophthalmopathy may need surgical treatment to
      alleviate ophthalmologic complications. The degree of reduction in proptosis
      following surgical intervention remains difficult to predict. OBJECTIVES: To
      elaborate a human model using cadaver orbits to study surgical management of
      Graves' ophthalmopathy. To evaluate quantitatively the contribution of each
      orbital wall decompression and their combinations in reduction in proptosis. To
      improve the ability to predict the degree of proptosis reduction according to the
      wall(s) chosen for decompression. METHODS: Artificial exophthalmos was created in
      12 cadavers' orbits by injecting a polysaccharide gel in the peribulbar and
      retrobulbar tissues. Proptosis reduction was measured following successive
      orbital decompression. RESULTS: Decompression of one wall produced a
      nonstatistical significant reduction in proptosis. The combination of the medial
      and lateral walls significantly reduced the proptosis by a mean of 4.2 mm. Three
      wall decompression gave a mean significant reduction of 6.6 mm, and when combined
      with the advancement of the lateral wall, it reduced proptosis by 12.5 mm.
      CONCLUSIONS: We created an experimental model for research and didactic purposes
      for surgical mangement of Graves' ophthalmopathy. With this model, to obtain 5 mm
      or more of proptosis reduction, three-wall decompression is required. Advancement
      of the lateral wall achieved a further reduction in proptosis. For a proptosis
      reduction of less than 5 mm, decompression of the medial and lateral walls is
      appropriate.

PMID- 17176800
TI  - Colorimetric evaluation of facial skin and free flap donor sites in various
      ethnic populations.
AB  - OBJECTIVE: To determine the optimal colour match for free tissue donor sites
      transferred to defects of the cheek and neck in a multicultural population.
      DESIGN: A prospective measurement of the colour of potential free flap donor
      sites and recipient sites in healthy volunteers. SETTING: A tertiary care
      academic health science centre. METHODS: Sixty-four healthy volunteers
      (Caucasian, black, South Asian, Southeast Asian) underwent noninvasive skin
      colour measurement of the cheek and neck, as well as a standard set of potential
      free tissue donor sites using a Minolta CR 300 (Konica-Minolta Canada; Markham,
      ON, Canada) chromameter. MAIN OUTCOME MEASURES: Measurement was done using
      derived colour measurements based on the Commission Internationale de l'Eclairage
      or International Commission on Light (CIE) L*a*b* tristimulus values. E* is a
      derived value of colour difference between sites using the L*a*b* measures.
      Statistical analysis was done using the Wilcoxon signed rank test. RESULTS:
      Variations exist between optimal donor sites in individuals of different ethnic
      backgrounds. Mean E* values suggest that in Caucasians, Southeast Asians, and
      South Asians, the upper extremity and trapezius flaps most closely approximate
      the recipient sites. In blacks, the variation in mean E* values is small and a
      wide variety of flaps provide a colour match to the cheek and neck. Luminance
      values support the observations regarding E*. DISCUSSION: Wide variations exist
      between individuals of different ethnic backgrounds in terms of optimal donor
      sites for the best colour match to surgical defects of the cheek and neck. In
      Caucasians, it appears that upper extremity sites, including the forearm and
      lateral arm flaps, provide the best colour match. Similar observations can be
      made in South Asians and Southeast Asians, with upper extremity flaps providing
      the best colour match. In blacks, there does not seem to be much variation in
      colour across the commonly used donor site, and a larger panel of flaps will
      provide an appropriate colour match in this subset of patients.

PMID- 17176801
TI  - Nasal cytology in the diagnosis and treatment of sinusitis in atopic and
      nonatopic children.
AB  - OBJECTIVES: To investigate the value of nasal cytology in the diagnosis of
      sinusitis and follow-up of atopic and nonatopic children before and after
      treatment and to compare the nasal cytologic findings with the radiologic
      findings. DESIGN: Open randomized investigation. SETTING: Ministry of Health,
      Ankara Diskapi Children's Hospital. METHOD: Fifty-five children with bronchial
      asthma and/or allergic rhinitis followed by the Allergy Department of the
      Ministry of Health, Ankara Diskapi Children's Education and Research Hospital and
      35 control children were evaluated for the following parameters: symptoms and
      signs of sinusitis, total serum immunoglobulin E level and eosinophil count,
      skinprick tests to common allergens, paranasal sinus radiographs, and nasal
      cytology (by the Rhinoprobe [Synbiotics Inc. London] method and wax paper blow).
      MAIN OUTCOME MEASURES: Nasal cytology, radiologic findings, and treatment.
      RESULTS: There were no significant correlations between radiologic and cytologic
      findings in any of the groups (p > .05). In both atopic and nonatopic chronic
      sinusitis patients, the Rhinoprobe method had results similar to the radiologic
      findings, and there was a significant relationship (p < .05). CONCLUSIONS: Nasal
      cytology is still a diagnostic tool in the follow-up and evaluation of chronic
      sinusitis in atopic children but should not be considered an adequate alternative
      to sinus radiography.

PMID- 17176802
TI  - Assessment of symptomatic patients after endoscopic sinus surgery with special
      reference to the frontal sinus: comparative radiologic analysis.
AB  - PURPOSE: To reveal the role of potential risk factors in frontal recess
      dissection (FRD), middle turbinate resection (MTR), sinonasal polyposis, and
      extension of disease in postoperative frontal sinus opacification by determining
      radiologic changes after endoscopic sinus surgery (ESS) in symptomatic cases
      using computed tomography (CT). STUDY DESIGN: Retrospective analysis of
      prospectively collected data from symptomatic patients after ESS. METHODS:
      Postoperative CT scans were taken in all symptomatic patients during their least
      symptomatic period or after maximal medical therapy. The radiologic findings of
      each sinus were compared, and the outcome of ESS was statistically evaluated.
      Furthermore, FRD, MTR, sinonasal polyposis, and extension of disease were
      analyzed for postoperative frontal sinus opacification. RESULTS: In our study,
      101 sinuses of 61 symptomatic patients were examined. A significant improvement
      in opacification in all sinuses was detected postoperatively. Multivariate
      analysis of all potential risk factors revealed that postoperative frontal sinus
      opacification was affected only by sinonasal polyposis (odds ratio [OR] 3.32; 95%
      confidence interval [CI] 1.04-10.58) and extension of disease (OR 16.93; 95% CI
      4.33-66.23). CONCLUSIONS: Our study revealed that surgical procedures such as FRD
      and/or MTR may not directly affect postoperative frontal sinus opacification. On
      the contrary, sinonasal polyposis and extension of disease seemed to be the main
      risk factors of this issue.

PMID- 17176803
TI  - Variation in tonsil size in 4- to 17-year-old schoolchildren.
AB  - OBJECTIVE: The purpose of this study was to evaluate the variation in tonsil size
      and prevalence of asymmetric tonsils in 4- to 17-year-old schoolchildren and the
      relationships between tonsillar hypertrophy and frequent tonsillitis, frequent
      fever, and sleep-related symptoms observed by parents. DESIGN: Cross-sectional
      study. SETTING: Six daycare centres, four primary schools, and four high schools.
      METHODS: Questionnaire and physical examination. MAIN OUTCOME MEASURES: The size
      of the tonsils was evaluated and scored on a 4-point scale. The
      interrelationships between tonsillar hypertrophy and other studied symptoms were
      examined. RESULTS: In the study, the parents of 1784 children, consisting of 803
      (45%) boys and 981 (55%) girls, completed the questionnaires. The prevalence
      rates of snoring, habitual snoring, observed apnea, and habitual observed apnea
      were 24.6%, 4.1%, 3.8%, and 0.9%, respectively. The results of tonsil scoring
      were grade 1, 62.7%; grade 2, 28.4%; grade 3, 3.3%; and grade 4, 0.1%. The
      prevalence rate of grade 1 tonsils was increasing, whereas the prevalence rates
      of grade 2 and 3 tonsils were decreasing with increasing age. Tonsil size peaked
      in 4- to 8-year-old children. The prevalence rates of tonsillar hypertrophy and
      asymmetric tonsils were 3.4% and 1.7%, respectively. Tonsillar hypertrophy was
      found to be significantly associated with male gender, a history of frequent
      tonsillitis, a history of frequent fever, often or always snoring, and often or
      always observed apnea. CONCLUSIONS: A tonsil size curve was developed in 4- to 17
      year-old schoolchildren. Children aged 4- to 8 years with oropharyngeal symptoms
      and particularly male gender should undergo consultation with otorhinolaryngology
      and pediatric pulmonology physicians for the evalution of adenotonsillar tissue.

PMID- 17176804
TI  - Combined extended midface degloving and endoscopic approach for resection of
      sinonasal lesions.

PMID- 17176805
TI  - Silent otitis media secondary to foreign body-induced otitis externa without
      mastoiditis: potential cause of brain abscess.

PMID- 17176806
TI  - Basal cell carcinoma involving the bilateral temporal bone.

PMID- 17176808
TI  - Health care and developmental status of children and their families.
AB  - A description of the health care and developmental status of children from a
      database created from a study done in a rural community of a province in South
      Africa. One hundred and ninety-eight parents/guardians responded to questions
      from structured interview guide. Findings suggest that most of the children are
      healthy. There appears to be evidence of some progress since the end of
      apartheid. There, however, still appears that much more is needed to meet the
      needs of the population living in this rural community.

PMID- 17176807
TI  - Overview of health and development of children and their families: health and
      functional status of the elderly.
AB  - This paper provides an overview of two studies designed to establish data bases
      that would aid in describing the health and development of children and their
      families and the health and functioning of the elderly in a rural community in
      South Africa.

PMID- 17176810
TI  - Parental views of the development of children in a rural South African community.
AB  - The purpose of this study is to describe how parents/guardians, reported on the
      development of their children, their perceptions of social support, satisfaction,
      and their level of depression. This is an aspect of a larger study conducted to
      create a database that will help to examine and describe the health and
      developmental status of children and their families. The results suggested that
      the parent's satisfaction had a direct correlation with the social support that
      they received from their families and the community. The study also revealed that
      the level of depression of the parents was directly associated with their degree
      of satisfaction.

PMID- 17176811
TI  - The treatment of hospital wastewater: an appraisal.
AB  - Hospitals discharge considerable amounts of chemicals and microbial agents in
      their wastewaters. Problem chemicals present in hospital wastewater belong to
      different groups, such as antibiotics, X-ray contrast agents, disinfectants and
      pharmaceuticals. Many of these chemical compounds resist normal wastewater
      treatment. They end up in surface waters where they can influence the aquatic
      ecosystem and interfere with the food chain. Humans are particularly exposed by
      the drinking water, produced from surface water. Microbial agents of special
      concern are multiresistant microbial strains. The latter are suspected to
      contribute to the spread of antibiotic resistance. In this paper, we will discuss
      the different approaches towards hospital wastewater treatment. The principle of
      uncoupling hospitals from public sewers warrants indepth evaluation by
      technologists and ecotoxicologists as well as public health specialists.

PMID- 17176809
TI  - Parents' perception of their children's development, perception of satisfaction,
      social support and level of depression.
AB  - The purpose of this study was to describe how parents and guardians in rural
      South Africa reported on the development of their children, their perception of
      social support and satisfaction, their level of depression, and the relationships
      that exist among the variables. The data from a larger research study were used
      to answer these questions: Is there a relationship between the child's
      development status and the parents/guardians level of satisfaction and social
      support? Is there a difference in the educational level of the parents/guardians
      and their perception of social support and the level of satisfaction? What is the
      percentage of parents/guardians working/not working? Is there a relationship
      between the status of work of the parents/guardians and the level of depression?
      Is there a relationship between the age of the parents/guardians and their level
      of depression? A convenience sample of 198 parents/guardians was recruited.
      Interviews were conducted using a structured interview guide. Relationships and
      differences were analyzed using Pearson's r correlation index, paired t-tests and
      regression analysis. The majority (73.7%) of the respondents were unemployed. No
      significant relationships were found between the child's developmental status and
      the parents/guardians perceived level of social support and satisfaction.
      However, the difference between the educational level of parents/guardians and
      the level of perceived social support was significant. Additionally, as the
      amount of family strains increased so did the parental level of depression.

PMID- 17176812
TI  - A case-cohort study to investigate concomitant waterborne outbreaks of
      Campylobacter and gastroenteritis in Soderhamn, Sweden, 2002-3.
AB  - Increased domestic, laboratory confirmed, Campylobacter notifications were
      reported in Siderhamn municipality, December 2002 and January 2003. Concurrently,
      during preliminary investigations a large outbreak of acute gastroenteritis was
      detected. Simultaneously, two studies were completed to identify risk factors for
      infection with Campylobacter and acute gastrointestinal infection (AGI): (1) a
      case-cohort study using Campylobacter cases (N = 101) with a large random sample
      from the municipal population as referents (N = 1000) and (2) a retrospective
      cohort study for the outcome AGI using the same sample. A postal questionnaire
      was used to collect demographic, clinical, water and food consumption data.
      Measures of association (risk ratio (RR), odds ratio (OR)) and 95% confidence
      intervals (CI) were calculated. Stool, environmental and water samples were
      tested by standard methods at Gavle Hospital and SMI laboratories respectively.
      In the case-cohort study, Camplylobacter cases were more likely than referents to
      consume communal water (OR = 12.6 (95% CI 1.7-92.3)). In the cohort study, risk
      of gastroenteritis was 2.3 times higher in those who consumed water (AR = 27.3%)
      than others (AR = 12%). Risk of illness was associated with the amount of water
      consumed in both studies. Campylobacter was detected in stools and Escherichia
      coli (E. coli) from routine communal water (CW) samples. Results suggest both
      Soderhamn outbreaks of Campylobacter and AGI were associated with consumption of
      CW. The method used strengthened epidemiological evidence and was efficient in
      the use of time and resources.

PMID- 17176813
TI  - Water ingestion during swimming activities in a pool: a pilot study.
AB  - Chloroisocyanurates are commonly added to outdoor swimming pools to stabilize
      chlorine disinfectants. The chloroisocyanurates decompose slowly to release
      chlorine and cyanuric acid. Studies conducted to determine if the
      chloroisocyanurates might be toxic to swimmers showed that they were not and that
      ingested cyanuric acid passed through the body unmetabolized. This fact was used
      to determine the amount of water swallowed during swimming activity. Fifty-three
      recreational swimmers, using a community swimming pool disinfected with cyanuric
      acid stabilized chlorine, participated in the study. The participants did not
      swim on the day before or after the test swim. The swimmers were asked to
      actively swim for at least 45 minutes and to collect their urine for the next 24
      hours. Cyanuric acid was measured in pool water using high performance liquid
      chromatography and porous graphitic carbon columns with UV detection. The urine
      sample assay required a clean-up procedure to remove urinary proteins and
      interfering substances. Results of the study indicate that non-adults ingest
      about twice as much water as adults during swimming activity. The average amount
      of water swallowed by non-adults and adults was 37 ml and 16 ml, respectively.
      The design for this study and the analytical methodology used to assay cyanuric
      acid in swimming pool water and human urine were effective for measuring the
      volume of water swallowed during swimming activity.

PMID- 17176814
TI  - Water consumption patterns in rural Bangladesh: are we underestimating total
      arsenic load?
AB  - Risk related to the ingestion of any water contaminants depends on many factors,
      including the daily per capita amount of consumed water relative to body weight.
      This study explored the water consumption pattern of a rural arsenic-affected
      population in Bangladesh. The study findings are likely to contribute to the risk
      estimation attributable to ingestion of arsenic and other drinking water
      contaminants. A total of 640 individuals participated in this cross-sectional
      study carried out in an arsenic-affected rural population in Bangladesh. In this
      study daily per capita water consumption for drinking purposes was found to be
      73.04 ml/kg/d (range = 71.24-74.84 ml/kg/d), which is higher than for both the US
      and Taiwan populations. This difference in per capita drinking water consumption
      might contribute to much higher lifetime cancer mortality and other morbidity
      risks from arsenic among the Bangladesh population compared to either the US or
      Taiwan populations. Arsenic is also ingested through cooking water which, if
      considered, might increase the risk further. The findings of this study highlight
      the urgent need for a holistic water supply programme for Bangladesh, with
      special emphasis on the arsenic-affected population.

PMID- 17176815
TI  - Occurrence of Cryptosporidium oocysts in US wastewaters.
AB  - Wastewater samples collected from ten wastewater facilities across the US were
      analyzed to determine the occurrence of indigenous Cryptosporidium oocysts using
      methods based on modifications of USEPA Method 1622. Wastewater facilities
      participating in this study ranged in size from 0.6 to 193 mgd average daily
      flow. A total of 289 wastewater samples were analyzed over a 15-month period.
      ColorSeed is a commercial product containing gamma-irradiated Cryptosporidium
      oocysts that have been permanently stained with a Texas Red dye. ColorSeed was
      used as an internal control with each sample to assess method performance. In
      500ml sample volumes, mean ColorSeed recoveries in raw influents and primary
      effluents were 26.1 17.7% and 33.0 +/- 17.9%, respectively. In 10 liter volumes
      of secondary effluent, mean ColorSeed recovery was 25.0 +/- 16.6%. Volumes
      analyzed for tertiary effluent samples ranged from 14.81 to 131.31 resulting in a
      mean ColorSeed recovery of 48.8 +/- 14.5%. Indigenous oocysts were detected in
      30% of raw influents, 46% of primary effluents, 58% of secondary effluents and
      19% of tertiary effluents analyzed. Indigenous oocyst concentrations ranged from
      <2 to 86 /liter across all wastewater matrices tested.

PMID- 17176816
TI  - Studies on defluoridation of water by tamarind seed, an unconventional
      biosorbent.
AB  - Tamarind seed, a household waste from the kitchen is used for the sorptive
      removal of fluoride from synthetic aqueous solution as well as from field water
      samples. Batch sorptive defluoridation was conducted under variable experimental
      conditions such as pH, agitation time, initial fluoride concentration, particle
      size and sorbent dose. Maximum defluoridation was achieved at pH 7.0.
      Defluoridation capacity decreases with increase in temperature and particle size.
      Further, defluoridation follows first order kinetics and Langmuir adsorption
      isotherm. Desorption was carried out with 0.1 N HCl and is 90 per cent. The
      surface and sorption characteristics were analysed using FTIR and SEM techniques.
      All these results indicate the involvement of energetic forces such as coulombic
      interaction in sorption. For domestic and industrial applications, defluoridation
      with 100% achievement and subsequent regeneration of adsorbent was performed with
      a household water filter and fixed bed column respectively.

PMID- 17176817
TI  - Rural communities' preferences for arsenic mitigation options in Bangladesh.
AB  - In the context of arsenic contamination of groundwater in Bangladesh, this paper
      analyses rural people's preferences for arsenic-free drinking water options. A
      particular focus is on rural households' willingness to pay for piped water
      supply which can provide a sustainable solution to the arsenic problem, and how
      the preference for piped water supply compares with that for various other
      household/community-based arsenic mitigation technologies. The analysis is based
      on data collected in a survey of over 2700 households in rural Bangladesh. Six
      arsenic mitigation technologies were selected for the study: three-kolshi
      (pitcher) method, activated alumina method (household-based and community-based),
      dugwell, pond sand filter and deep tubewell (handpump). The survey results
      indicate that, after taking into consideration the initial and recurring costs,
      convenience, associated risks and the advantages and disadvantages of each
      selected technology, the preference of the rural people is overwhelmingly in
      favor of deep tubewells, followed by the three-kolshi method. The analysis
      reveals a strong demand for piped water in both arsenic-affected and arsenic-free
      rural areas, and scope of adequate cost recovery. Between piped water and other
      arsenic mitigation technologies, the preference of the rural people is found to
      be predominantly in favor of the former.

PMID- 17176818
TI  - Application of microbial risk assessment on a residentially-operated bio-toilet.
AB  - The Sustainable Sanitation System is a new wastewater treatment system that
      incorporates a non-flushing toilet (Bio-toilet) that converts excreta into a
      reusable resource (as fertilizer or humus for organic agriculture) and reduces
      the pollution load to environments of the rivers, the lakes, and the sea.
      However, the risk of exposure to pathogens should be considered, because
      excrement is stored in the Bio-toilet. The aim of the present work is to analyze
      the health risk of dealing with the matrix (excreta and urine mixed with sawdust)
      of the Bio-toilet. Therefore, the fate of pathogenic viruses was investigated
      using coliphages as a virus index, and the modeling of the die-off rate in matrix
      was introduced. Then the microbial risk assessment was applied to a Bio-toilet
      that was actually used in a residential house; the infection risks of rotavirus
      and enterovirus as reference pathogens were calculated. According to the lab
      scale experiment using coliphages for investing the die-off rate of viruses in
      the Bio-toilet, Qbeta had a higher die-off, which was greatly influenced by the
      water content and temperature. On the other hand, T4 showed a lower rate and was
      independent of water content. Therefore, these two phages' data were used as
      critical examples, such as viruses having high or low possibilities of remaining
      in the Bio-toilet during the risk assessment analysis. As the result of the risk
      assessment, the storage time required for an acceptable infectious risk level has
      wide variations in both rotavirus and enterovirus cases depending on the phage
      that was used. These were 0-260 days' and 0-160 days' difference, respectively.

PMID- 17176819
TI  - Quantitative detection of E. coli, E. coli O157 and other shiga toxin producing
      E. coli in water samples using a culture method combined with real-time PCR.
AB  - Recent water related outbreaks of shiga toxin producing E. coli O157 have
      resulted in increased attention of the water industry to this potentially deadly
      pathogen. Current methods to detect E. coli O157 and its virulence genes are
      laborious and time-consuming. Specificity, sensitivity and simple use of a real
      time PCR method makes it an attractive alternative for the detection of STEC E.
      coli O157. This study describes the development and application of real-time PCR
      methods for the detection of E. coli O157, shiga toxin genes (Stx1 and Stx2) and
      E. coli. The specificity of the methods was confirmed by performing colony-PCR
      assays on characterized bacterial isolates, demonstrating the applicability of
      these assays as rapid tests to confirm the presence of E. coli or E. coli O157
      colonies on culture plates. Sensitive culture-PCR methods were developed by
      combining culture enrichment with real-time PCR detection. This rapid method
      allowed detection of low concentrations of E. coli O157 in the presence of high
      concentrations of non-O157-E. coli (1:104). Culture-PCR methods were applied to
      27 surface water and 4 wastewater samples. E. coli O157 and both Stx genes were
      detected in two wastewater samples, whereas only E. coli O157 was detected in two
      surface water samples. Culture-PCR methods were not influenced by matrix effects
      and also enabled quantitative (MPN) detection of E. coli in these samples.

PMID- 17176820
TI  - The case for the rope-pump in Africa: a comparative performance analysis.
AB  - The conventional handpump is the most popular technology choice for improved
      potable water supplies in rural sub-Saharan Africa. To date, however, it has
      failed to deliver satisfactory levels of sustainability, largely due to
      inadequate maintenance capacity. An alternative option to standardised imported
      handpumps is the locally manufactured rope-pump, which is considerably cheaper
      and easier to maintain but has been rejected in the past due to fears of impaired
      water quality. This paper presents the key aspects of a study in northern Ghana
      which compared the performance of rope-pumps with that of conventional handpumps,
      to determine whether or not the rope-pump provides a viable alternative for
      community water supplies across the subcontinent. User interviews, sanitary
      surveys, water quality analyses and technical performance measurements were used
      to develop a comparative performance analysis for the two pump types. The
      findings of the study indicated that the rope-pump out-performed the conventional
      handpump on the majority of counts and that, contrary to widespread perceptions,
      there was no significant difference between pump types with respect to the impact
      on microbiological water quality. Consequently, the rope-pump provides a
      significant technological opportunity to improve water supply sustainability in
      Africa.

PMID- 17176821
TI  - Drinking water consumption patterns in Sweden.
AB  - Estimates on drinking water consumption are necessary in risk assessments on
      microbial hazards in drinking water. Large differences in consumption habits
      between countries have been reported. In order to establish estimates for the
      Swedish population, water consumption data from a waterborne outbreak
      investigation (157 people), a small water consumption study (75 people) and a
      large study on health and environmental factors (10,957 people) were analysed. A
      lognormal distribution for the daily direct/cold water intake in litres with mu =
      - 0.299 and sigma = 0.570 was fitted to the quantitative data, representing the
      general population. The average daily consumption of tap water as plain drinking
      water and as heated tap water, e.g. in coffee and tea, was 0.86 +/- 0.48 l and
      0.94 +/- 0.69 l, respectively. Women consumed more cold tap water than did men,
      while men appeared to have a higher consumption of heated tap water. Cold tap
      water intake was highest in the oldest age group, (> or =70 years). The
      consumption of bottled water was very low (mean 0.06 l/d) when compared to other
      countries.

PMID- 17176822
TI  - Reevaluation of the toxicity of chlorinated water and the usefulness of MX as an
      index.
AB  - Changes in the toxicity in chlorinated water after chlorine addition were
      examined. For toxicity evaluation, the chromosomal aberration test and the
      transformation test were conducted as indexes of initiation activity and
      promotion activity, respectively, in the carcinogenesis process. Activity
      inducing chromosomal aberrations in chlorinated Lake Biwa water gradually
      decreased over time after chlorination. In contrast, activity inducing
      transformations determined by the two-stage assay gradually increased. Thus,
      toxicity that decreases or increases is present in chlorinated water.
      Furthermore, activity inducing transformations determined by the non-two-stage
      assay gradually decreased over time. This direction of change is opposite to that
      of activity inducing transformations determined by the two-stage assay and is
      consistent with that of activity inducing chromosomal aberrations. The drastic
      decrease in initiation activity detected as activity inducing chromosomal
      aberrations could be the main cause for the decrease in activity inducing
      transformations determined by the non-two-stage assay (an index of the sum of
      initiation and promotion activity). MX change was quantitatively consistent with
      those of activity inducing chromosomal aberrations and transformations determined
      by the non-two-stage assay. On the other hand, directions of changes in
      concentrations of typical by-products such as chloroform were consistent only
      with that of activity inducing transformations determined by the two-stage assay.
      Findings of this study suggest that MX is appropriate as an index for comparing
      the carcinogenicity of tap water near and far from a water purification plant.

PMID- 17176823
TI  - An attempt to estimate the global burden of disease due to fluoride in drinking
      water.
AB  - A study was conducted to examine the feasibility of estimating the global burden
      of disease due to fluoride in drinking water. Skeletal fluorosis is a serious and
      debilitating disease which, with the exception of one area in China, is
      overwhelmingly due to the presence of elevated fluoride levels in drinking water.
      The global burden of disease due to fluoride in drinking water was estimated by
      combining exposure-response curves for dental and skeletal fluorosis (derived
      from published data) with model-derived predicted drinking water fluoride
      concentrations and an estimate of the percentage population exposed. There are
      few data with which to validate the output but given the current uncertainties in
      the data used, both to form the exposure-response curves and those resulting from
      the prediction of fluoride concentrations, it is felt that the estimate is
      unlikely to be precise. However, the exercise has identified a number of data
      gaps and useful research avenues, especially in relation to determining exposure,
      which could contribute to future estimates of this problem.

PMID- 17176824
TI  - Effect of glutathione on arecanut treated normal human buccal fibroblast culture.
AB  - BACKGROUND: Experimental studies have shown arecanut to be a cytotoxic substance
      with mutagenic and carcinogenic potential. OBJECTIVE: The present study was
      undertaken to evaluate the effect of glutathione on arecanut treated human buccal
      fibroblast culture and its potential as a chemopreventive agent. MATERIALS AND
      METHODS: Fibroblast culture was done in Dulbecco's Modified Eagle's Medium MEM)
      supplemented with 10% Fetal Calf Serum (FCS) and antibiotic at 370C degrees in an
      atmosphere of 5% carbon di-oxide and 95% air. The fibroblast cells were subjected
      to different concentrations of aqueous extracts of raw and boiled arecanut.
      Fibroblasts were plated in two 24-well culture plates and in each plate, cells
      were dividt,ednto 2 groups; 600gg microml of reduced glutathione was added to the
      first group of cells; subsequently, aqueous extracts of raw and boiled arecanut
      at least and highest concentrations i.e., 20j. microml and 100lg microml were
      added to the first group of cells in the respective plates whereas the second
      group served as a control. The morphological alterations and cell survival were
      assayed at 24, 48, 72, and 96 hours. Results Morphologically, the initial (10
      hours) attached fibroblast cells were converted from spheroidal shape towards
      hexagonal and finally to a fully extended spindle shaped configuration. The three
      morphological types of fibroblasts at 48 hours were F-I, F-II and F-III. Aqueous
      extract of raw arecanut exhibited significant cytotoxicity (p < .0 001) at all
      time periods studied, when compared against the control values of untreated
      fibroblasts. Addition of reduced glutathione to cultures showed a significant (p
      < 0. 001) reduction in cytotoxicity, as indicated by higher optical density
      values and morphological reversion to the spindle-shaped configuration. Co
      CONCLUSION: Addition of glutathione reduced the cytotoxic and morphological
      alterations of the fibroblasts treated with aqueous extracts of both raw and
      boiled arecanut.

PMID- 17176825
TI  - Assessment of the efficacy of an indigeniously developed pulse oximeter dental
      sensor holder for pulp vitality testing.
AB  - Current routine methods of assessment of pulp vitality rely on stimulation of
      nerve fibres and give no direct indication of blood flow within the pulp. Pulse
      oximeter is a proven, atraumatic method of measuring vascular status, by
      evaluating oxygen saturation. This study explores the use of customized dental
      pulse oximeter sensor holder to assess pulpal vascular oxygen saturation in
      permanent teeth. Pulse oximeter readily differentiated between known vital and
      nonvital teeth. Vital teeth consistently provided oxygen saturation values that
      were lower than the values recorded on the patient's fingers. Pulse oximeter is
      an accurate, atraumatic clinical alternative to the present electrical and
      thermal methods of assessing pulp vitality in teeth.

PMID- 17176826
TI  - Expression of Toll-like receptors 2 and 4 in gingivitis and chronic
      periodontitis.
AB  - Periodontal disease is the major cause of adult tooth loss and is commonly
      characterized by a chronic inflammation caused by infection by oral bacteria.
      Members of Toll-like receptor (TLR) family recognize conserved microbial
      structures, such as bacterial lipopolysaccharides, and activate signaling
      pathways that result in immune responses against microbial infections. The aim of
      the present study was to assess the mRNA expression of TLR-2 and TLR-4 in
      gingivitis and chronic periodontitis. Gingival tissue samples were collected from
      patients with chronic periodontitis, gingivitis, and healthy controls. Total RNA
      was extracted and RT-PCR was done for TLR-2 and TLR-4. The results showed that
      TLR-2 was significantly increased in gingivitis compared to TLR-4 expression and
      decreased in chronic periodontitis.

PMID- 17176827
TI  - Evaluation of salivary nitric oxide levels in oral mucosal diseases: A controlled
      clinical trial.
AB  - Lichen planus is a common dermatologic disease to manifest in the oral cavity.
      Recurrent aphthous ulcers are the most common ulcers of the oral cavity causing
      discomfort to the patients. These two diseases have different clinical
      manifestations which require appropriate treatment after correct diagnosis.
      Though numerous etiological factors have been proposed for these diseases, their
      true etio-pathogenesis is not yet established and therefore all therapies are
      palliative and none is effective universally. In light of this, the role of
      nitric oxide as a mediator in the etio-pathogenesis of these diseases was
      considered. The present study was undertaken to note the salivary nitric oxide
      levels as measured through its product nitrite in oral mucosal diseases like
      lichen planus and recurrent aphthous ulcers and also to ascertain whether
      salivary nitric oxide level has a role to play as a pathophysiological mediator
      in these diseases

PMID- 17176828
TI  - Prevalence of oral lesions in relation to habits: Cross-sectional study in South
      India.
AB  - BACKGROUND: Smoking, drinking and chewing tobacco product, common habits in India
      have been positively associated with oral lesions. No study has been conducted in
      this part of Tamilnadu regarding the prevalence of oral lesions in relation to
      habits. METHODS: A hospital based cross-sectional study was carried out at Ragas
      Dental College, Chennai. Already existing data of two thousand and seventeen
      consecutive patients from sub-urban areas of Chennai, who attended the outpatient
      department, at Ragas Dental College, for dental complaints during a period of
      three months in 2004, who underwent oral examination and interviewer based
      questionnaire was used. RESULTS: Oral soft tissue lesions were found in 4.1% of
      the study subjects. The prevalence of leukoplakia, OSF and oral lichen planus was
      0.59%, 0.55%, and 0.15% respectively. The prevalence of smoking, drinking
      alcoholic beverages and chewing was 15.02%, 8.78% and 6.99% respectively. Smoking
      and chewing were significant predictors of leukoplakia in this population.
      DISCUSSION: The prevalence of leukoplakia, OSF and oral lichen planus in our
      study population is similar to those found in other populations. The prevalence
      of consumption of alcoholic beverages in our study population was higher when
      compared to the Indian National Sample Survey study. However the prevalence of
      smoking and chewing was found to be lower. Smokers were more likely to develop
      smoker's melanosis compared to other lesions. Among those who consumed alcoholic
      beverages alone, the prevalence of leukoplakia was higher compared to other
      lesions. OSF was the most prevalent lesion among those who chewed panmasala or
      gutkha or betel quid with or without tobacco.

PMID- 17176829
TI  - Root coverage with free gingival autografts--a clinical study.
AB  - AIM: To assess the percentage of root coverage with autogenous free gingival
      grafts. MATERIALS & METHODS: Ten non-smoking patients with Miller's class I or
      class II recessions were included in the study. The clinical parameters such as
      recession depth, recession width, probing pocket depth, clinical attachment level
      and width of the keratinized gingiva were recorded at the baseline, at the end of
      1 month, 3 months, and 6 months after the surgical procedure. Autogenous free
      gingival grafts harvested from the palatal mucosa were used to cover the denuded
      roots. RESULTS: Four out of ten sites showed 100% root coverage. A mean
      percentage of 80.3% of root coverage was achieved.

PMID- 17176830
TI  - Florid cemento-osseous dysplasia: Review and report of two cases.
AB  - Only three Indian patients of florid cemento-osseous dysplasia have been reported
      (less than 2%), according to the review of recent literature (2003). This makes
      the occurrence of FCOD a relatively rare phenomenon. The age group may vary from
      19-76 years and typically presents in the fourth and fifth decade. In most of the
      cases, patients do not have family history of the disease. We report two cases
      showing classic radiologic features. The diagnosis of our cases were made
      radiographically.

PMID- 17176831
TI  - Solitary intraosseous neurofibroma of mandible.
AB  - Solitary intraosseous neurofibroma is a rare benign non-odontogenic tumor.
      Although neurofibromas occur predominantly as a feature of neurofibromatosis
      affecting the soft tissue, a few cases of solitary intraosseous neurofibromas of
      the jaw have been reported. We herewith report a case of solitary intraosseous
      neurofibroma of mandible in a middle-aged woman with a discussion on its
      clinical, radiological, and histopathological presentation along with review of
      cases.

PMID- 17176832
TI  - Mucormycosis presenting as palatal perforation.
AB  - Mucormycosis is an opportunistic fungal infection that is caused by normally
      saprobic organism of the class Zygomycetes. The main form of mucormycosis are
      pulmonary and rhinocerebral. Rhinocerebral mycormycosis typically starts in the
      maxillary antrum, particularly in poorly controlled diabetics. Invasion of
      surrounding tissue can cause necrotizing ulceration of palate with a blackish
      slough and exposure of bone. A case of mucormycosis presenting as palatal
      performation is discussed in this article.

PMID- 17176833
TI  - [Role of mitochondria in reglulation of endothelial cell hyperpolarization to
      acetylcholine].
AB  - We investigated the regulation of sustained endothelial hyperpolarization to
      acetylcholine in the rat aortic endothelial cells by mitochondria. Protonofore
      CCCP and rotenone, an electron transport chain complex I inhibitor, agents that
      cause mitochondria depolarization, inhibited the sustained hyperpolarization of
      endothelial cells. This effect was unlikely to be mediated by the free radicals
      since hydrogen peroxide was shown to hyperpolarize endothelial cells. It is
      concluded that mitochondrial Ca2+ uptake is essential in prolongation of
      endothelial hyperpolarization to acetylcholine.

PMID- 17176834
TI  - [The effects of alpha-linolenic acid on the functioning of the isolated heart
      during acute myocardial ischemia/reperfusion].
AB  - Many studies indicate that dietary omega-3 polyunsaturated fatty acids (PUFAs)
      have the cardioprotective properties. But majority of experiments were carried
      out with using omega-3 PUFAs from marine fish oil. The purpose of this study was
      to determine effects of the plant-derived omega-3 PUFA (alpha-linolenic acid (a
      LA) on postischemic myocardial dysfunction, lipid peroxidation and antioxidant
      enzymes activity. Male Wistar rats (250-300 g) were divided into 4 groups (n = 10
      12 each). In control group (1) were intact rats. The hearts from 2-nd group of
      animal were exposed to 20 min of global ischemia followed by 40 min reperfusion
      according to the Langendorff technique. The 3-rd and 4-th groups of animal
      received of the plant-derived oil (a-LA), which is a precursor of
      eicosapentaenoic acid and was used as a dietary supplement in dose 0.1 mg/kg per
      day for 4 weeks. The hearts from 4-th group of animal were also exposed to
      ischemia/ reperfusion. Analysis of myocardial phospholipid fatty acid content
      showed that consumption of the plant-derived 6-LA for 4 weeks changes fatty acid
      profile through incorporation of b-LA in cell membranes. It also reduced content
      of omega-6 PUFAs in membrane phospholipids. In 3-rd group content of a-LA and EPA
      were increased by 1.5- and 3.5-times, respectively, whereas content of AA was
      reduced by 1.7-times. The development of ischemia/ reperfusion in 2-nd group
      caused increase of free AA content in heart tissue by 3.5-times, whereas in 4-th
      group this increase was only by 1.4-time. Ischemia/reperfusion of the isolated
      rat heart in 4-th group was accompanied by reduced leukotriene C4 and thromboxane
      B2 production in 3-times and 1.9-times, respectively in comparison to 2-nd group.
      The time of myocardial function recovery after ischemia (heart rate, left
      ventricular development pressure), was shorter compare to 2-nd group. Also in 4th
      group end-diastolic pressure and coronary perfusion pressure during reperfusion
      period were significantly lower. Dietary omega-3 PUFAs resulted in remarkable
      decrease of reperfusion arrhythmias in 4-th group (in 3.8-times) and limited the
      oxidative stress through decrease free radical and lipid peroxidation production.
      In this group of animals the activity of antioxidant enzymes (superoxide
      dismutase and catalase) after ischemia/reperfusion were higher than in 2-nd
      group. We suggest that dietary supplement of the plant-derived alpha-LA for 4
      weeks have cardioprotective effects similar to the effects of fish oil.

PMID- 17176835
TI  - [Neuroprotective effect of quercetin during experimental brain ischemia].
AB  - The neuroprotective action by water-soluble form of quercetin was examined in
      gerbils after transient forebrain ischemia. The animals were exposed to 7 min of
      bilateral common carotid artery occlusion. Hippocampal CA 1 area was examined 7
      days after ischemia-reperfusion. The average density of CA1 pyramidal neurons and
      GFAP-positive glial cells were counted in sham operated group, in ischemic group
      and in the groups treated with water-soluble form of quercetin. It was shown that
      quercetin revealed protective effect by decreasing of delayed neuronal death and
      reducing reactive astrogliosis after ischemia-reperfusion.

PMID- 17176836
TI  - [Elucidation of the mechanisms of acetylcholine constrictor action on the portal
      vein and its intrahepatic branches].
AB  - Intraportal administration of acetylcholine (Ach) to anesthetized rats evokes
      endothelium depended, atropine resistant and phentholamine sensitive constriction
      of hepatic portal vessels. On the contrary to Ach action sodium
      nitroprussideresulted in vasodilatation in this vessel. On the isolated segment
      of portal vein (PV) similar results were obtained; at the same time the blockade
      of nicotinic acetylcholinic receptors by nicotine (in high concentration),
      tubocurarine or tetrodotoxine diminished constrictor reactions of PV to Ach. We
      concluded that described vasomotor effects of Ach in the hepatic portal bed are
      carried out through nicotinic Ach-receptors localized on endothelial cells and
      (or) adrenergic neurones in the wall of portal vessels. These cells synthesize
      and release mediators, possibly, noradrenaline which causes constriction of
      portal vessels.

PMID- 17176838
TI  - [Effect of amber acid on the kidney function in gentamycin-induced nephropathy in
      white rats].
AB  - The amber acid neutralized by 10 % solution of NaOH in a concentration of 250
      mmoL/L was administered subcutaneously simultaneously with intraperitonal
      injection of gentamycin in a doze of 10 mg/kg(bw) once a day during 7 days to the
      ten nonlinear white male rats, weight 100-120 g exposed to the water-induced
      diuresis. In these experiments the positive action of an amber acid as energy
      substratum on some renal function tests was shown: improvement of reabsorbtion in
      proximal tubules, proved by proteinuria decrease, subsequent normalization of
      glomerular filtrations followed by uremia reduction and diminishing of other
      signs of acute renal failure.

PMID- 17176837
TI  - [Effect of thromboxane B2 on morphological features of apoptosis in cultured rat
      hepatocytes exposed to hepatotropic substances].
AB  - Thromboxanes (TX) are known to have damaging effect on a liver but their
      influence on the cell death, in particular on hepatocyte apoptosis and its
      morphological features is not investigated enough. Cell death of the rat
      hepatocytes was investigated in primary culture by double vital staining with
      fluorescent nuclear stains Hoechst 33342 and propidium iodide and by electron
      microscopy. It was established that exogenous Tx B2 increases the amount of
      hepatocytes with early stages of apoptosis - the condensed chromatin and nucleus
      and cell size reduction. The changes in a percentage of hepatocytes with
      morphological features of the late stages of apoptosis - fragmented nuclei and
      division on apoptotic bodies were not revealed. Tx B2 intensified the carbon
      tetrachloride action on hepatocyte apoptotic death and increased chromatin
      condensation. Tx B2 application to hepatocytes injured by chenodeoxycholic acid
      significantly increased the amount of cells with a final stage ofapoptosis.

PMID- 17176839
TI  - [State of the adaptation reactions in the correction process of the negative
      effect of the stress-factors of chemical nature].
AB  - The prolonged influence of lead and fluorine lowers gradually adaptative reserves
      of organism. Gradual diet supplementation with such bioprotectors as pectin,
      calcium and triovitum results in renewal of prooxidant-antioxidant balance, that
      is confirmed by the elevation of antioxidant defence' integral coefficient from
      0,09 to 1. The method of estimation of the states of the organism adaptive
      reactions and the power of action of chemical nature stress-factors in the
      process of correction of the adaptive violations, using the value of antioxidant
      defence' integral coefficient is offered. This method is based on correlation of
      indexes of antioxidant system activity and intensity of lipoperoxidation
      products.

PMID- 17176840
TI  - [Mechanism of protective effect of amphiphilic compounds during hypertonic
      hemolysis of erythrocytes].
AB  - Antihemolytic effect of various amphiphilic compounds under conditions of red
      blood cell hypertonic hemolysis at different temperatures (0 and 37 degrees C)
      and cell exposure to diamide was investigated. The level of maximum antihemolytic
      activity and values of efficient concentrations for all studied substances were
      lower at 0 degrees C if compared with 37 degrees C. Exposure of erythrocytes to
      diamide (5 and 10 mmol/l) did not change cell sensibility to hypertonic medium.
      There has been demonstrated a temperature-dependent decrease in the efficiency of
      studiedsubstances under hypertonic hemolysis of erythrocytes exposed to 10 mmol/l
      diamide. Found reduction in efficiency of amphiphiles at low temperature and at
      high concentration of diamide was probably caused by similar changes of
      structural and dynamic state of erythrocyte membrane.

PMID- 17176841
TI  - [Reaction of organism to the reduced partial oxygen pressure in inhaled air of
      highly-qualified female sportsmen in mountain condition].
AB  - Functional respiration system (FRS) state and its changes in highly-qualified
      sportsmen after decrease of the O2 partial tension (pO2) in inhaled air was
      investigated. Significant decrease of oxygen regimen efficacy accompanied by
      alteration of FRS was registered in the first day of altitude hypoxia. In
      sportsmen well adapted to hypoxia and whose professional activity is associated
      with low and extremely low pO2 in inhaled air there are no changes in FRS after
      moving to mountain conditions.

PMID- 17176843
TI  - [Effect of L-arginine on antioxidant system and NADH2-depended
      methemoglobinereductase activity in rat blood].
AB  - We investigated the influence of L-arginine, a nitric oxide precursor, on the
      state of hemoglobin and basic parts of the antioxidant system. We revealed the
      negative influence of NO hyperproduction on the oxygen transport by haemoglobin,
      which is manifested by the increase of MetHb concentration and decrease of the
      MetHb-reductase activity. Also increase of glutathioneperoxidase,
      glutathionereductase and glutathion-etransferase activities were documentated; at
      the same time catalase activity in the erythrocyte hemolisate was decreased. This
      can point on the dominating role of glutathione in the protection of erythrocyte
      membrane and hemoglobin under the condition of oxidative stress, which was
      induced by NO hyperproduction.

PMID- 17176842
TI  - [The effect of rithmocor on the structural and functional state of erythrocyte
      membranes and athlete's adaptation to intensive training loads].
AB  - Intensive training process is accompanied by the oxidative stress with alteration
      of homeostatic balance and functional possibility of cardio-vascular system
      followed by decrease of oxygen transport and tissue hypoxia. The tissue hypoxia
      and increase of oxygen active forms level worsen structural and functional status
      of erythrocyte membranes that led to the temporary anaemia. In this article was
      shown that Rithmocor corrected these alterations and increased adaptation of
      sportsmen to the intensive training load (increase of endurance). An improvement
      of erythrocyte membranes status resulted in the increase of intracorpuscular
      haemoglobin content the critical parameter for the anaemia development. It has
      been established that Rithmocor causes an increased of sportsmen endurance to the
      intensive training load and therefore could be recommended for use in this
      situation.

PMID- 17176844
TI  - [Physiological aspects of ubiquinone supplementation in cardiovascular
      pathology].
AB  - Ubiquinone (coenzyme Q10) is an obligatory component of the respiratory chain in
      the inner mitochondrial membrane coupled to ATP synthesis and acts as an
      antioxidant. Its additional localization in the different subcellular fractions
      is probably associated with its multiple functions in the cell. Coenzyme Q10
      deficiency has been observed in patients with congestive heart failure, angina
      pectoris, coronary artery disease, cardiomyopathy, hypertension, mitral valve
      prolapse. The clinical benefits of Q10 supplementation in prevention and
      treatment of cardiovascular diseases have been observed in many trials.
      Ubiquinone is the introduction of the metabolic drugs and may be recommended to
      patients with cardiovascular pathologies as an adjunct to conventional treatment.

PMID- 17176845
TI  - [Alcohol abuse as a risk factor for ARDS].
AB  - Morbidity and mortality rates of ARDS (acute respiratory distress syndrome) are
      high in patients with a history of chronic alcohol abuse. In addition to
      susceptibility to lung infection, alteration of local cellular functions in the
      lung has recently been proposed as a new mechanism of exacerbation of ARDS in
      patients with a history of chronic alcohol abuse. Clinical studies and studies
      using animal experiments have shown that a decrease in lung glutathione levels is
      associated with exacerbation of ARDS in chronic alcohol abuse. In the alcoholic
      lung, depletion of glutathione increases oxidative stress derived from activated
      neutrophils, resulting in decreased surfactant production, apoptosis and
      increased permeability of alveolar epithelial type II cells, in which TGF-beta1
      may be involved. Acetoaldehyde has been suggested to be involved in the mechanism
      of exacerbation of ARDS by inducing lung remodeling through stimulation of
      fibronectin expression following nicotinic acetylcholine receptor stimulation and
      CREB activation in chronic alcohol abuse. More recently, antagonists of
      angiotensin II type-1 receptor (AT1 receptor) have been shown to prevent
      glutathione depletion, increase in TGF-beta1 expression and lung edema in
      endotoxemic rats with chronic alcohol administration. On the other hand,
      macrophage-derived prostaglandin E2 plays a protective role at an initial phase
      of ARDS by inhibiting cytokine production by macrophages and extravascular
      invasion of activated neutrophils. Our recent studies have shown that LPS-induced
      COX-2 expression and subsequent prostaglandin E2 production in rat alveolar
      macrophages are inhibited by ethanol incubation in vitro and ethanol
      administration in vivo. Only a decade has passed since alcohol abuse was
      demonstrated to be associated with increased mortality of ARDS and future studies
      are needed to clarify the mechanism underlying alcohol-induced exacerbation of
      ARDS.

PMID- 17176846
TI  - [Gastroenterological endoscopic findings in alcoholic liver disease patients-
      comparison of daily drinkers at physical check up].
AB  - We compared findings of alcoholic liver disease patients used by
      gastroenterological endoscopes (31 patients hospitalized in Hyogo Prefectural
      Amagasaki Hospital: AA group, and 156 patients hospitalized in Suma Red Cross
      Hospital: AL group) with physical checkup patients (48 daily drinkers: A group,
      and 99 non drinkers: C group). Esophageal varices were seen by the majority of AA
      group, and the frequencies of esophageal cancers were also high in the gullet
      changed to morbid state. Although these things were seen AL group, there were few
      as compared with AA group. Moreover, frequencies of esophagitises in AL group
      were higher than C group (p < 0.05), though it was the same level in C group and
      AA group. In a strange stomach trouble, as for AL and A group, there were a lot
      of gastric erosions compared with C group (p < 0.05). However, AL group compared
      with the other groups, the gastric polyps were few (especially C group, p <
      0.01). In the duodenum, changing to a morbid state, ulcers were high frequency
      (5/31) in AA group compared with the other groups (p < 0.05). Moreover AA and AL
      groups had a lot of polyps high frequency compared with C group (p < 0.05), and
      duodenitises were high frequencies in AL group compared with A and C group (p <
      0.05, p < 0.01). It seemed stronger that the digestive organs changing to morbid
      state was tendency depended on alcohol consumption and the influence of smoking
      was not able to be disregarded.

PMID- 17176847
TI  - [Review of relationship between alcohol drinking and esophageal varices].
AB  - The adequate treatment for patients with thrombocytopenia, encephalopathy,
      ascites and esophagogastric varices due to portal hypertension are very
      important. This review explains the relations between heavy drinkers and symptoms
      of portal hypertension, especially with regard to the form of esophageal varices.
      Between heavy drinker and non-heavy drinker, there was no significant differences
      for form, color and red color sign of varices. In heavy drinker, the ratio of
      strong red color sign might be higher than non-heavy drinker. Value of portal
      pressure in heavy drinker might be higher. These results can bring sudden
      variceal bleeding in heavy drinkers.

PMID- 17176848
TI  - [Alcoholic liver diseases and hepatitis virus C in Japan].
AB  - Recently incidence of alcoholic liver disease (ALD) has been increasing in Japan
      associated with an increase in alcoholic beverage consumption. There have been a
      large number of reports about the relationship between alcohol and
      hepatocarcinogenesis, but it remains controversial. In the present study, we
      addressed the recent trend in incidence of ALD including liver cirrhosis (LC),
      and hepatocellular carcinoma (HCC) in heavy drinkers in Japan. We carried out
      nation-wide survey by asking for the hospitals that are approved by the Japanese
      Society of Gastroenterology for recent aspects of in-patients with ALD. Except
      for HCC, percentage of ALD without viral hepatitis is more than 70%, which is
      increased when compared to the national survey carried out in 1992. In alcoholic
      LC patients, those who did not have viral hepatitis were 81%. However, the
      percentage of HCC without viral hepatitis was 34% of all of the heavy drinkers
      with HCC. Regarding the case in our university hospital, 138 cases (32%) of 432
      patients with HCC were heavy drinkers. However, regarding in our general
      hospital, 15 cases of 23 patients with HCC (61%) were heavy drinkers. In
      conclusion, since the consumption of alcohol is increasing in Japan, the
      frequency and number of cases of alcoholic liver cirrhosis are increasing. Viral
      hepatitis infection, however, still plays an important role in
      hepatocarcinogenesis in heavy drinkers.

PMID- 17176849
TI  - [Molecular logic of alcohol and taste].
AB  - Ethanol, a main constituent of every alcohol beverage, has long been calling our
      attention to its gustatory effect. Recent molecular dynamics studies have
      suggested that ethanol as well as other tastants in foods, when taken in the oral
      cavity, gives rise to a taste signal which is expressed via reception at taste
      cells in the taste bud, intracellular signal transduction in collaboration with G
      proteins and effecters, and signal transmission to synapsed taste neurons, and/or
      simultaneous reception at and signal transduction in somatosensory neurons. The
      taste of ethanol and its acceptability are then recognized and judged at the
      higher center, with generation of various physiological phenomena in the body. We
      have tried to make an all-inclusive DNA microarray analysis, demonstrating that
      when a rat tongue is stimulated with a drop of aqueous ethanol in vivo, several
      particular genes are specifically up- or down-regulated in trigeminal ganglions.
      These initial gene expression changes at peripheral neurocytes might in whole or
      in part trigger some of the ethanol-associated gustatory and bodily response. The
      importance of defining a related molecular logic is emphasized to understand
      academic and industrial significances of this unique food constituent, ethanol.

PMID- 17176851
TI  - [In vitro activity of methylrosaniline chloride (gentian violet) as disinfectant
      against Candida spp. and Trichosporon spp. isolated from blood samples].
AB  - OBJECTIVE: Methylrosaniline Chloride (MRC) is recognized as a disinfectant, but
      recently is rarely used in the clinic, because of its cytotoxicity when used
      continuously with conventional concentrations (1% MRC). We have reported the
      antibacterial activity of MRC with lower concentration against Methicillin
      resistant Staphylococcus aureus (MRSA). In this study, we evaluated the
      antifungal activity of MRC with lower concentrations. MATERIAL AND METHODS:
      Antifungal activities of MRC against Candida spp. and Trichosporon spp. were
      tested. All strains tested were isolated from 106 blood or intravenous catheter
      samples at Juntendo University Hospital from 1995 to 2004. Minimum inhibitory
      concentrations against fungi were assayed by agar dilution, under both aerobic
      and anaerobic conditions. RESULTS: A 0.01% or less concentration of MRC solutions
      showed marked antifungal activity against Candida spp. and Trichosporon spp.
      under aerobic or anaerobic conditions. CONCLUSION: A 0.01% or less concentration
      of MRC should be reevaluated for the control of fungal infection and MRSA
      infection control.

PMID- 17176850
TI  - [Is "the resistance to negative reinforcement" a feature of alcohol dependence
      syndrome?].
AB  - In 1979, "Alcoholism Diagnosis Committee, the Ministry of Health and Welfare"
      established the diagnostic criteria for alcohol dependence syndrome, which
      included "the resistance to negative reinforcement". The author raises a question
      about this criterion which indicates the condition that "an individual continues
      to drink despite alcohol-related physical diseases, rejection by his/her family
      or economic poverty and drinking-related criminal problem." The author defines
      this condition not as "resistance to negative reinforcement" but as "resistance
      to punishment." Furthermore, the author can not find the data supporting that
      "the resistance to negative reinforcement" in the correct sense exists in the
      individuals with alcohol dependence syndrome. In a theoretical sense, an opposite
      idea seems to exist. There is an observed fact that can be regarded as a
      phenomenon that explains the involvement of "negative reinforcement" in
      enhancement of psychological dependence as in the case of the secondary
      development of psychological dependence. Consequently, the author would have to
      say that defining "the resistance to negative reinforcement" as one of common
      features of alcohol dependence syndrome or one of diagnostic criteria for alcohol
      dependence syndrome is inappropriate.

PMID- 17176852
TI  - [Isolation rate and antifungal drug susceptibility of yeast like fungi isolated
      from blood or vascular catheter].
AB  - Increased resistance of strains to antifungal drugs has gained increasing
      attention. We studied the status of fungal isolation from blood and vascular
      catheters at Juntendo University Hospital from 1994 to 2002. The major fungi
      isolated were Candida albicans, Candida parapsilosis, Candida glabrata and
      Candida trophicalis, or 86% yeast-like fungi. Isolation of these fungi from
      vascular catheters is increasing. The effectiveness of 6 anti-fungal agents
      against 116 yeast-like fungi was measured by microdilution. In antifungal
      activity of micafungin (MCFG), MIC90, was < or = 0.03 g/mL for C. albicans, C.
      glabrata and C. tropicalis. MCFG showed the strongest antifungal activity among
      the drugs tested for above Candida spp.. Five of 37 strains of C. albicans were
      resistant to fluconazole (FLCZ) showing MIC > or =64 g/mL. These strains were
      also resistant to itraconazole (ITCZ) but MICs of MGFG, flurocytosine (5-FC) and
      amphotericin B (AMPH-B). Two of 38 strains of C. parapsilosis are resistant to
      flurocytosine (5-FC) showing MIC > or =64 g/mL. There is no resistant strain of
      fungi (yeast-like organisms) tested against AMPH-B. Six patients from whom
      resistant fungi were isolated from blood and vascular catheters have severe
      diseases and/or are have just undergone a major surgical operation. These results
      indicate that it is vital for deep mycosis to start early treatment with
      appropriate drugs selected based on rapid detection and identification of
      organisms and the drug susceptibility of organisms.

PMID- 17176853
TI  - [Evaluation of rapid diagnostic kits for the detection of group A streptococcus
      to Streptococcus pyogenes and Streptococcus spp. with Lancefield's group A
      antigen].
AB  - We studied the basic performance of eight rapid diagnostic kits for the detection
      of Group A streptococcus by immunochromatography under the same conditions. Kits
      were the; QuickVue Dipstick Strep A (Sumitomo Seiyaku Biomedical Co., Ltd.),
      TESTPACK Plus STREP A (ABBOTT JAPAN Co., Ltd), CLEAVIEW STREP A (Nihon Schering
      K. K.), QuickVue STREP A (Wako Pure Chemical Industries, Ltd), ImmunoCard STAT!
      STREP A (TFB, INC.), DIPSTICK 'Eiken' STREP A (Eiken Chemical Co., Ltd.), Rapid
      Testa Strep A (Daiichi Pure Chemical Co., Ltd.), and StatCheck Strep A (KAINOS
      Laboratories, Inc.). Four of these kits, i.e. QuickVue Dipstick Strep A, TESTPACK
      Plus STREP A, Rapid Testa Strep A, and StatCheck Strep A showed sensitivity at
      1.0 x 10(5) CFU/mL (1.0 x 10(4)CFU/test) with all of S. pyogenes tested, while
      the Anginosus group and S. dysgalactiae subsp. equisimilis with Lancefield' s
      group A antigen showed sensitivity very similar to S. pyogenes. Of these strains,
      S. dysgalactiae subsp. equisimilis formed a beta-hemolytic colony resembling that
      of S. pyogenes on sheep blood agar, and was sensitive to bacitracin. It is thus
      indispensable to identify the colony using biochemical tests such as the PYR
      (pyrrolidonylarylamidase production) test. In using rapid diagnostic kits for the
      detection of Group A streptococcus, it is important to rule out the possibility
      of Group A streptococcus other than S. pyogenes in throats. Severe invasive group
      G streptococcal infections are increasing recently. Concerning S. dysgalactiae
      subsp. equisimilis, it is especially important to conduct these identification
      tests.

PMID- 17176854
TI  - [An epidemiological study of outbreaks of Salmonella enterica serovar paratyphi A
      occurred in two Chinese families after traveled to different areas of China].
AB  - We reported two familial clusters of paratyphoid fever after travel to China
      occurring in the same Yokohama ward from September to October 2002. Six
      Salmonella enterica serovar Paratyphi A (S. Paratyphi A) strains, 3 each from 2
      clusters, were isolated and their characteristics analyzed using phage typing,
      susceptibility to antibiotics, and patterns of restriction endonuclease-digested
      DNA fragments in agarose gel following pulsed-field gel electrophoresis (PFGE).
      Mutations in genes for gyrA and parC, which determine sensitivity to
      fluoroquinolones, were also investigated. All isolates showed the same
      characteristics, i.e. "untypable", employing bacteriophages, resistant to
      antibiotics nalidixic acid and fosfomysin, and decreased susceptibility to
      fluoroquinolones. No difference was observed in PFGE patterns after digesting
      with 4 restriction enzymes, Xba I, Bin I, Spe I, and Xho I. We also found that
      the gyrA gene, which is one of the quinolone-resistance-determining regions
      (QRDR), was mutated at position 83 from serine to phenylalanine (from TTC to TCC)
      in all 6 strains. Other QRDR's, parC were not mutated commonly in them. Hearing
      from patients and family members, it was apparent that these 2 families had been
      contacted neither in Japan nor in China during ill or incubation period of
      paratyphoid fever, although a member of one cluster had a familial relationship
      with one of another family. It was also reported by them that typhoid fever is
      endemic in both of the areas of their visits. From these results, it was
      suggested that these 2 cluster cases were infected separately in China with the
      progeny of the same clone which is endemic in these regions.

PMID- 17176855
TI  - [A collective review of Vibrio vulnificus infection in Japan].
AB  - Vibrio vulnificus is found globally in marine coastal waters. Infection with this
      organism, via ingestion of raw shellfish or exposure to marine water, can cause
      necrotizing fasciitis and sepsis, which have high mortality and short latency. In
      Japan, many cases have been reported since 1980, mainly from hospitals in western
      prefectures. However, because of the sporadic nature of infection outbreaks, a
      thorough epidemiologic survey has not been done. We studied the epidemiological
      and clinical characteristics of Vibrio vulnificus infections reported in Japan
      from 1975 to 2005. We identified 185 cases using the medical article search
      engines Ichushi (Japan Medical Abstracts Society), CiNii (Citation Information by
      National Institute of Informatics), and PubMed over 30 years. The median age of
      patients was 59. The number of male patients was eight times the number of female
      patients; however, no significant difference in mortality was found between
      genders. In yearly distributions of patients, 20 cases were reported in 2001, a
      year in which we experienced more rainfall and a longer rainy season in Northern
      Kyushu. In monthly distribution, about 80% of cases were reported from July to
      September when sea water temperatures rise. About 40% of cases were reported in
      four prefectures around the Ariake Sea. The underlying disease indicated liver
      dysfunction in 90% of patients, but mortality was the same regardless of the
      infection pathway (oral ingestion or wound). Because of its rapid aggravation and
      high mortality rate, public education is important to prevent new cases. It is
      also highly recommended that patients with preexisting liver dysfunction avoid
      raw fish and limit exposure to marine water during the summer.

PMID- 17176856
TI  - [Distribution of Clostridium tetani in topsoil from Sagamihara, central Japan].
AB  - Despite reports of Clostridium tetani being isolated from soil in Kanazawa,
      Okinawa, and Tokyo, Japan, little has been studied about C. tetani distribution
      in other regions. We studied C. tetani in topsoil samples collected from private
      gardens, public road shoulders, a university campus, mountains, and fields in
      Sagamihara. C. tetani occurred in 8 of 35 soil samples (22.9%) and tetanus toxin
      in 7 of the 8 C. tetani-positive samples (87.5%). Contamination was clearly
      higher in soils from mountains near Tsukui-gun (Kanagawa Prefecture), Minamitsuru
      gun, and Uenohara and Koshu cities (Yamanashi Prefecture) than in other regions.
      These findings suggest that tetanus toxin-producing strains of C. tetani tend to
      inhabit the topsoil of western Sagaminaha region, as a geographical feature.

PMID- 17176857
TI  - [Molecular epidemiological analysis of an outbreak of Campylobacter jejuni using
      restriction enzyme double-digestion technique for genotyping of isolates by
      pulsed-field gel electrophoresis].
AB  - In an outbreak of gastroenteritis in elementary school students and their
      families in Chiba Prefecture, Japan, Campylobacter jejuni was isolated from the
      stools of 14 patients who developed diarrheal illness after a one-day bus trip.
      C. jejuni was also isolated from the stools of 3 patients not going on the bus
      trip. Pulsed-field gel electrophoresis (PFGE) analysis was done on 17 isolates of
      C. jejuni to study genetic relationships among them. PFGE profiles of isolates
      treated with restriction enzymes Sma I, Ksp I and Kpn I were separated into 9,
      10, and 10 types, but the relationship between PFGE profiles and epidemiological
      profiles was unclear. Dendrograms of PFGE of isolates double-digested with both
      Sma I and Ksp I were typed into D1, D2, D3 and D4, and profiles compared to
      profiles of serotyping and flagellin typing of isolates and epidemiological
      profiles to evaluate genetical and epidemiological relationships. Thirteen
      isolates of PFGE type D1 possessed serotype G and flagellin type Al and were
      isolated from patients going on the bus trip. Type D2 isolated from a student
      going on the bus trip and type D3 isolates from two students not going on the bus
      trip had serotype B and flagellin type A2. C. jejuni of PFGE type D4, serotype
      UT, and flagellin type A3 was also isolated from a student not going on the trip.
      Our results show that at least two outbreaks of C. jejuni occurred simultaneously
      in people related to the school. Restriction enzyme double-digestion PFGE was
      thus useful in the molecular epidemiological analysis of the C. jejuni outbreak.

PMID- 17176858
TI  - [Clinical usefulness of the (1-->3)-beta-D-glucan measurement kit using the
      improved alkaline pretreatment method--comparison with conventional method].
AB  - We had reported that the rate of non-specific reaction in measurement of (1-->3)
      beta-D-glucan was decreased by improvement of the alkaline pretreatment reagent
      of Fungitec G-test MK (MK assay). To compare the clinical usefulness between
      conventional MK assay and new MK assay using improved alkaline pretreatment
      reagent, 121 plasma samples were tested. The sensitivity, specificity, positive
      predictive value (PPV), negative predictive values (NPV) in conventional MK assay
      were 91.7%, 85.3%, 44.0% and 98.8%, respectively. Those in new MK assay were
      75.0%, 91.6%, 52.9% and 96.7%, respectively. On the other hand, area under the
      curve (AUC) of receiver operating characteristic (ROC) analysis in conventional
      and new MK assay was 0.9175 and 0.9123 without a significant difference. It has
      been recognized that the sensitivity in conventional MK assay is higher than
      those in other beta-glucan assays. Then, the specificity of new MK assay was
      improved by using improved alkaline pretreatment reagent, without decreasing the
      sensitivity. Thus, the present findings indicate that the new MK assay is
      clinically quite useful.

PMID- 17176860
TI  - [Survival by a young woman with malnutrition due to alcoholism and eating
      disorders and with acute respiratory distress syndrome due to severe pneumonia
      who showed increased serum neutrophil elastase activity].
AB  - A 30-year-old woman with malnutrition due to alcoholism and eating disorders was
      found to have acute respiratory distress syndrome (ARDS) and sepsis due to severe
      Streptococcus pneumoniae pneumonia. S. pneumoniae was detected by an in vitro
      rapid immunochromatographic assay for S. pneumoniae antigen in urine on the day
      of admission and by blood culture 2 days after admission. Symptoms and laboratory
      findings improved after treatment with sivelestat sodium hydrate, antibiotics,
      and mechanical ventilation. Treatment with sivelestat sodium hydrate also
      decreased serum neutrophil elastase activity. This case demonstrates the
      usefulness of early treatment with sivelestat sodium hydrate in ARDS due to
      severe pneumonia.

PMID- 17176859
TI  - [A case of severe falciparum malaria successfully treated with intravenous
      artesunate and continuous hemodiafiltration].
AB  - We report a 54-year-old Japanese man who contracted severe falciparum malaria
      after visiting West African countries. The patient presented with Plasmodium
      falciparum parasitemia of 10% on admission and was successfully treated with
      intravenous artesunate combined with continuous hemodiafiltration. We found that
      intravenous artesunate had excellent antimalarial activity with rapid parasite
      clearance and that few adverse effects were observed compared to those reported
      for intravenous quinine treatment. Supportive therapy was indispensable for
      saving the life of the patient. Few cases of intravenous artesunate treatment are
      reported in Japan because the drug has not been legally registered. We wish to
      emphasize the efficacy of intravenous artesunate with general supportive therapy
      in the treatment of possible imported severe malaria patients in Japanese medical
      settings.

PMID- 17176861
TI  - [A case of toxocariasis with eosinophilic pleural effusion].
AB  - A 76-year-old man admitted for general malaise with fever was found in clinical
      examination on admission to have eosinophilic pleural effusion, peripheral
      eosinophilia, and a slightly elevated inflammatory reaction. Immunological
      examination, including microplate ELISA, showed a high titer of specific antibody
      against Toxocara canis in both the serum and pleural effusion. We started
      treatment using albendazole, and found inflammatory findings and serum IgE were
      ameliorated. Parasitic disease is an important consideration in the differential
      diagnosis of eosinophilic pleural effusion, and serology is useful in screening
      for this.

PMID- 17176862
TI  - [Case report of disseminated nocardiosis complicated in an elderly person with
      pneumoconiosis].
AB  - Nocardia is typically regarded as an opportunistic infection, with pulmonary
      nocardiosis frequently disseminated to organs hematogenous by, and nearly half of
      these cases resulting in complicated nocardia brain abscess. Disseminated
      nocardia has a dismal prognosis with high mortality, and should be checked for
      multiple organs including the brain when nocardiosis is diagnosed. We describe
      the successful treatment of nocardia brain abscesses in an immunocompetent older
      people with pneumoconiosis by combining trimethoprim-sulfamethoxazole and
      ciprofloxacin. Patients had no history of fever, headache, or respiratory
      symptoms such as cough, or sputum until the acute hemiplegia episode. Nocardia
      infection is not as rare as generally assumed and should be considered as a
      possibility in the elderly due to its high mortality.

PMID- 17176863
TI  - [A clinical study of renal pelvic and ureteral cancer].
AB  - We investigated the clinicopathological features of 52 patients with transitional
      cell carcinoma of renal pelvic and/or ureter who underwent surgical treatment at
      Tokyo Medical University Hachioji Medical Center from April, 1992 to June, 2005.
      The patitents consisted of 38 males and 14 females, ranging from 29 to 86 years
      old with a median age of 68 years old. The mean follow-up period was 39 months.
      Pathologicaly, 32 cases were less than pT2 and 20 cases were pT3. Findings of
      lymphatic and venous invasion were present in 10 and 8 cases, respectively. The
      infiltration pattern (INF) of gamma was observed in 9 cases. The overall cause
      specific survival rate was 95.8% at 1 year, 87.7% at 3 years and 80.6% at 5
      years, respectively. According to univariate analysis, the high stage of tumor,
      the presence of lymphatic and/or venous invasion, the inclusion of infiltration
      pattern of gamma and positive reginonal lymph nodes indicated a significantly
      poor prognosis. On the other hand, multivariate analysis using Cox proportional
      hazards regression revealed the presence of infiltration pattern of gamma as the
      most significant predictor of survival.

PMID- 17176865
TI  - [Two cases of adult tethered cord syndrome with surgical treatment].
AB  - We report two cases of adult tethered cord syndrome alleviated by untethering
      surgery. Case 1 was a 35 year-old female who complained of incontinence while
      exercising. Radiograph revealed spinal disraphism below the L5 level. In
      addition, magnetic resonance imaging (MRI) showed low placed conus medullaris at
      the levels of S2 and sacral intradural lipoma. Further urodynamic studies
      demonstrated normal sphincteric function and autonomous bladder. Diagnosis
      resulted in the decision to perform an untethering operation. The patient had
      increased bladder compliance after surgery for untethering and has continued to
      be continent 16 months post-operatively. Case 2 was a 27-year old female who
      complained of apprehension to void and straining during urination. Radiograph
      demonstrated spinal disraphism below the S2 level and MRI revealed low placed
      conus medullaris at the level of S5 and sacral intradural lipoma. Urodynamic
      examination verified normal sphincteric function and autonomous bladder. After
      complete diagnosis, an untethering operation was performed. Post-operatively,
      bladder compliance and urinary sensation normalized. Furthermore, the patient
      spontaneously delivered a baby 3 years after having the untethering operation.

PMID- 17176864
TI  - [Indication of repeat prostate biopsy for the diagnosis of prostate cancer].
AB  - There is no standard criterion for repeat prostate biopsy in cases with a
      negative initial biopsy. We retrospectively analyzed our experience of repeat
      prostate biopsy to establish its indication for the diagnosis of prostate cancer.
      From April 1997 to March 2005, 35 consecutive patients underwent repeat prostate
      biopsy at the department of Urology, Asahikawa Medical College Hospital because
      of clinically suspicious prostate cancer despite a negative initial biopsy. We
      compared patients' age, number of cores obtained during repeat biopsy, digital
      rectal examination findings, total prostate volume, the time from the first to
      the last biopsy, total prostate specific antigen (PSA) value, free PSA/total PSA
      ratio, PSA density and PSA velocity between cancer-positive and cancer-negative
      groups. Prostate cancer was detected in 17 of 35 patients (49%). Fifteen patients
      with prostate cancer were diagnosed by the first repeat biopsy and other 2
      patients were diagnosed by the second repeat biopsy. A statistically significant
      difference was only noted in age and PSA density. Persistently elevated total PSA
      and a higher PSA density in cases with a negative initial biopsy might be a good
      indication of repeat prostate biopsy for the diagnosis of prostate cancer.

PMID- 17176867
TI  - [A case of adult Wilms' tumor --review of the Japanese literature].
AB  - The patient was a 23-year-old-woman who was referred to our hospital with chief
      complaints of right flank pain and macroscopic hematuria. Right radical
      nephrectomy was performed with the diagnosis of right renal cancer.
      Histopathological examination revealed Wilms' tumor of favorable histology, stage
      I according to the National Wilms Tumor Study classification. She received
      adjuvant chemotherapy consisting of actinomycin D and vincristine at another
      hospital. One year and three months later, she developed lung metastasis. She
      underwent partial pulmonary resection, and then received chemotherapy. She is
      presently disease-free more than forty months after the initial operation. Wilms'
      tumor is rare in adults and has a poor prognosis compared with that in children.
      We analyzed 112 cases in the Japanese literature from 1981 to 2004. The mean age
      was 36.9 years, with males and females equally affected. No difference was found
      between the left and right sides in frequency of tumor. We also examined the
      relationship between histological features and prognosis based on 43 Japanese
      reports. Twenty-two of the 43 (51%) cases had unfavorable histology. The 2-year
      survival rate with unfavorable histology was 18%, while that with favorable
      histology was 87%. The 2-year survival rates for stages under II and over III
      were 67% and 27%, respectively. Based on these findings, we conclude that the
      prognosis of adult Wilms' tumor is very poor since many patients have unfavorable
      histology and no effective treatment guidelines have been established.

PMID- 17176866
TI  - [Pancreatic and duodenal metastases from renal cell carcinoma 13 years after
      radical nephrectomy: a case report].
AB  - A 52-year-old male was admitted to our hospital complaining of orthostatic
      vertigo, fatigue and weight loss, who underwent right total nephrectomy for renal
      cell carcinoma(RCC) with curative operation 13 years ago (in 1992). Endoscopic
      examination revealed a submucosal tumor with erosion in the duodenum. The
      diagnosis made from the biopsy specimens was metastatic RCC in the duodenum.
      Abdominal CT scan revealed that his metastasis has spread to the pancreas. Five
      million units of interferon a was administered intramuscularly three times a week
      for 1 month. He received blood transfusions and palliative care. He died 5 months
      later because of disease progression. Metastases of RCC have been often reported
      in the lungs, the liver, and the bones, but rarely in the gastrointestinal tract.
      This is a very rare case of metastatic RCC in the duodenum, which was diagnosed
      13 years after curative right nephrectomy. Since late recurrence is
      characteristic of renal cell carcinoma, careful long-term follow-up is needed. To
      our knowledge, this is the 19th case of duodenal metastasis from RCC reported in
      the literature.

PMID- 17176868
TI  - [Simultaneous renal cell carcinoma and urothelial carcinoma in ipsilateral
      kidney, report of two cases].
AB  - Two cases of simultaneously developed renal tumors (renal cell carcinoma and
      renal pelvic urothelial carcinoma) in the ipsilateral kidney are reported. These
      underwent radical surgery under the diagnosis of renal cell carcinoma or renal
      pelvic urothelial carcinoma, respectively. The risk of incorrect preoperative
      diagnosis is discussed in terms of insufficient surgical margins. The liberal use
      of frozen section diagnosis and more radical resection if applicable may be the
      key to solve such dilemmas.

PMID- 17176869
TI  - [Renal cell carcinoma metastatic to the ovary].
AB  - A 45-year-old woman underwent left radical nephrectomy in April 2002.
      Pathological diagnosis was a renal cell carcinoma, clear cell subtype, pT3a, v(
      ), NO. One year later, abdominal ultrasound revealed a left ovarian tumor which
      had an enlargement tendency. A laparoscopic bilateral salpingooophorectomy was
      performed. Immunohistochemical analysis confirmed the diagnosis of metastatic
      ovarian renal cell carcinoma. This is the 20th case in the literature.

PMID- 17176870
TI  - [A case of mesoblastic nephroma in adulthood].
AB  - We report a rare adult case of mesoblastic nephroma. A right renal mass was
      detected in a 51-year-old woman by ultrasonography. The radiographic examination
      revealed that the mass was the hypovasucular tumor, but there was a possibility
      of a malignant tumor. We therefore operated on her for right radical nephrectomy.
      The tumor was 40 X 52 mm in size and had several cysts. Based on the histological
      analysis, we diagnosed it as congenital mesoblastic nephroma consisting of
      spindle cells.

PMID- 17176871
TI  - [A case report of left renal cell carcinoma with tumor thrombus extending into
      the right atrium].
AB  - A case report of left renal cell carcinoma with tumor thrombus extending into the
      right atrium is reported. A 76-year-old woman was found to have a left renal
      tumor with tumor thrombus extending into the inferior vena cava and right atrium
      by computed tomographic-scanning. Left nephrectomy and removal of an intra-atrial
      tumor thrombus were performed under a cardiopulmonary bypass. The post-operative
      course was uneventful and the patient was discharged from the hospital 22 days
      postoperatively. The pathological diagnosis was clear cell carcinoma. After
      surgery, the patient received interferon-gamma. However, the patient developed
      lung metastases 26 months after the operation and is currently being observed
      while receiving interferon-alpha.

PMID- 17176872
TI  - [Left renal pelvic tumor 32 years after calyco-ileo-vesiconeostomy].
AB  - This is a case report of left renal pelvic tumor found 32 years after left calico
      ileo-vesiconeostomy. The patient has undergone right nephrectomy for absence of
      renal function at 26 years-old and left urinary reconstruction was performed
      using the intestine for pyelo-ureteral junction obstruction at 28 years old
      because of bilateral congenital hydronephrosis. Later he was treated for
      recurrent left renal stone with percutaneous nephrolithotripsy, nephrolithotomy
      and extracorporeal shock wave lithotripsy. When he was 56 years old,
      macrohematuria appeared. He received left nephrectomy under the diagnosis of left
      renal pelvic tumor.

PMID- 17176873
TI  - [Xanthogranulomatous pyelonephritis presenting a subcutaneous mass in the lower
      abdomen: a case report].
AB  - A 72-year-old female presented with the complaint of left lower abdominal
      swelling in May, 2005. Laboratory analysis revealed elevated white blood cell
      counts and C-reactive protein. Abdominal computed tomography showed left ureteral
      calculi, left hydronephrosis and a mass extending through the perinephric space,
      psoas major muscle into the left flank and lower abdomen. Echo-guided needle mass
      biopsy was performed. Histopathological findings revealed xanthogranulomatous
      changes. Under the diagnosis of diffuse xanthogranulomatous pyelonephritis
      extended into psoas muscle and subcutaneous tissue, antibiotic therapy was given
      for 5 months. After reduction of subcutaneous mass, left nephroureterectomy was
      performed. Histopathological findings revealed xanthogranulomatous pyelonephritis
      and ureteritis. Postoperative course was uneventful without any relapse of
      inflammation.

PMID- 17176874
TI  - [A case of emphysematous cystitis: a case report].
AB  - A 86-year-old woman presented with asymptomatic gross hematuria,and visited our
      hospital, and a vesicorectal fistula was suspected from a computed tomographic
      (CT) scan. She had a lower abdominal mass and urinary retention on arrival.
      Pclvic CT demonstrated intramural gas in the urinary bladder,which suggested a
      diagnosis of emphysematous cystitis. Cystoscopy demonstrated reddish mucosa and
      gas within the bladder wall. The gross hematuria was improved and the intramural
      gas disappeared on a CT scan after urinary drainage and antibiotic therapy.
      Although emphysematous cystitis is almost always cured with conservative therapy,
      an accurate diagonosis and prompt treatment are required because rarely
      emphysematous cystitis can result in rupture of the urinary bladder and lead to
      septic shock.

PMID- 17176875
TI  - [Extra-adrenal pheochromocytoma (paraganglioma) of the urinary bladder without
      typical symptoms: a case report].
AB  - A 33-year-old female patient was admitted to our department with bladder tumor.
      It was detected by a magnetic resonance imaging (MRI) in an examination for
      hysteromyoma. She had neither hypertention, gross hematuria nor the classic
      symptoms of cathecholamine excess during micturition. The diameter of the tumor
      was 33 mm. Cystoscopic examination showed a submucosal tumor in the left anterior
      wall of the bladder. Percutaneous needle biopsy was performed. Biopsy specimens
      revealed as a pheochromocytoma. 131 I-MIBG scintigraphy showed abnormal
      accumulation in the bladder, and no abnormal accumulation in the other lesion.
      Endocrinologic examination disclosed increased levels of serum and urinary
      noradrenalin. On May 18, 2005, partial cystectomy was performed. The
      catecholamine levels normalized after partial cystectomy. The patient has been
      followed up for 9 months and shown no recurrence.

PMID- 17176876
TI  - [Prostatic duct adenocarcinoma with pagetoid spread on the glans penis: a case
      report].
AB  - A 75-year-old male visited our division with asymptomatic erythema on the glans
      penis which he first noticed six months earlier. The patient underwent total
      cystoprostatectomy under the diagnosis of urothelial carcinoma of the urinary
      bladder four years earlier. At the time, the prostatectomy specimen incidentally
      revealed a prostatic acinar adenocarcinoma at the bilateral peripheral zone. A
      skin biopsy of the erythema revealed intraepithelial Paget's cells, and the
      patient underwent total penectomy under the diagnosis of extramammary Paget's
      disease. Histopathological examination revealed continuous intraepithelial
      Paget's cells from the glans penis to the urethral navicular fossa, and a ductal
      carcinoma was detected beneath the urethral mucosa to the excisional margin.
      Because the Paget's cells expressed cytokeratin 20, the tumor was diagnosed as
      Pagetoid spread rather than Paget's disease. Re-examination of the previous
      prostatectomy specimen revealed prostatic duct adenocarcinoma with prostatic
      acinar adenocarcinoma. Therefore, the final diagnosis was prostatic duct
      adenocarcinoma with Pagetoid spread to the glans penis. Follow up at nine months
      revealed neither local recurrence, nor distant metastases, although no adjuvant
      therapy has been given.

PMID- 17176877
TI  - [Prostate small cell carcinoma: report of two cases that differed in treatment
      responsiveness].
AB  - Case 1 : A 76-year-old man with a chief complaint of dysuria had an elevated
      prostate specific antigen (PSA) level of 24.9. He underwent a transperineal
      needle biopsy of the prostate, and the histopathological diagnosis was prostatic
      small cell carcinoma. The cancer was clinically diagnosed as T3bN1M1 with
      multiple lung metastases. He started receiving hormonal therapy. After three
      months of hormonal therapy, the multiple lung metastases disappeared. Thereafter,
      the serum PSA level and the tumor volume increased and he died 12 months from the
      start of therapy. Case 2: A 79-year-old man was referred to our hospital with a
      chief complaint of dysuria. The serum level of PSA was elevated to 10.4.
      Transperineal prostate biopsy revealed prostatic small cell carcinoma. The cancer
      was clinically diagnosed as T3bN1M1, and hormonal therapy was started.
      Subsequently, although his serum PSA level declined, his condition worsened
      rapidly and he died five months after the start of therapy.

PMID- 17176878
TI  - [Two cases of spermatic cord leiomyosarcoma].
AB  - A 72-year-old man and a 59-year-old man presented with painless hard swelling of
      left scrotal content. They underwent left high orchiectomy with clinical
      diagnosis of spermatic cord tumor. The pathological examination revealed
      leiomyosarcoma. The former had adjuvant radiation therapy locally. These are the
      28th and 29th cases of spermatic cord leiomyosarcoma in Japan.

PMID- 17176879
TI  - [Topical steroids and tacrolimus for the treatment of atopic dermatitis].

PMID- 17176880
TI  - Impact of peripheral arterial disease and acute ischemic stroke.
AB  - Peripheral arterial disease (PAD) is associated with coronary artery disease
      (CAD) and stroke, but data on the relationship between PAD and acute ischemic
      stroke are lacking. Therefore, we investigated this relationship. A total of 101
      patients were enrolled on admission to Harasanshin General Hospital (Fukuoka,
      Japan) with their first ischemic stroke. All 101 patients underwent cranial CT
      and/or brain magnetic resonance imaging, duplex ultrasonography of the
      extracranial carotid arteries, and transthoracic echocardiography. The subjects
      were aged 41 to 92 years. PAD was present in 81/101 patients (80.2%), including
      57/73 (78.1%) with small artery occlusion, 11/13 (84.6%) with large artery
      occlusion, and 13/15 (86.7%) with cardiogenic embolism. In 42 of these 81
      patients (51.9%), PAD was asymptomatic. Serum apoprotein A1 levels were
      significantly higher and the intima-media thickness was significantly greater in
      the patients with PAD than in those without PAD. The modified Rankin scale score
      was significantly higher on admission in patients with PAD than in those without
      PAD. Stepwise logistic regression analysis revealed that the apoprotein A1 level
      and the modified Rankin scale score on admission were strongly associated with
      the occurrence of stroke in patients with PAD. Our results suggest that PAD is
      frequently associated with acute ischemic stroke. It may be important to perform
      screening for PAD in patients who have suffered an ischemic stroke.

PMID- 17176881
TI  - Aneurysmal bone cyst of the capitate: case report and a review emphasizing local
      recurrence.
AB  - We herein report the case of a 15-year-old boy with cystic lesion of the
      capitate. Magnetic resonance imaging showed that the lesion demonstrated
      homogenous low-intensity on T1-weighted imaging and homogenous high intensity on
      T2-weighted imaging. The lesion was treated by curettage and autologous bone
      grafting. The histological specimen from the cystic wall showed loose fibrous
      tissue with capillary vessels and extravasated red blood cells. The cystic lesion
      was filled with blood, suggesting that the cystic lesion was actually an
      aneurysmal bone cyst. The present case is the second reported case of aneurysmal
      bone cyst of the capitate. No recurrence has been observed during the 4 years
      since operation. We also review the literature related to ABCs of the hand with
      special emphasis on local recurrence.

PMID- 17176882
TI  - [Picture in clinical hematology: subcorneal pustular dermatosis complicated with
      a myeloproliferative disorder].

PMID- 17176883
TI  - [The role of GATA1 mutation in acute megakaryocytic leukemia].

PMID- 17176884
TI  - [Homeobox genes and leukemia: the role of HOX-MEIS interaction].

PMID- 17176885
TI  - [Bone marrow failure due to telomerase complex gene mutations].

PMID- 17176886
TI  - [Pure red cell aplasia: clinical manifestations and treatment].

PMID- 17176887
TI  - [The role of cord blood stem cell transplantation in children; a retrospective
      analysis of 39 cases in a single institute].
AB  - We report the results of 39 children who underwent cord blood stem cell
      transplantation (CBSCT) at our institute during the period from February 1996 to
      July 2005. The patients consisted of 9 with non-malignant disease, 26 with
      malignant disease and 4 with Epstein-Barr virus (EBV) associated disease. The
      median age of the patients was 4 years and 8 months (range, 6 months to 16 years
      2 months). The median infused cell dose was 4.9 (range, 1.7-11.4) x 10(7)/kg.
      Thirty-four transplants were from HLA-mismatched donors, and 33 patients
      underwent a tacrolimus-containing regimen for GVHD prophylaxis. As for CBSCT as
      the first transplant, 3 out of 4 children with non-malignant disease achieved
      engraftment after CBSCT with the use of a reduced-intensity conditioning regimen.
      For acute leukemia, 3 patients out of 5 in their first remission and 2 out of 9
      in advanced stage at CBSCT continue in remission at the time of writing. Fourteen
      patients received CBSCT as a second or a third transplant. None of 4 patients who
      underwent CBSCT as rescue therapy after rejection/graft failure achieved
      engraftment. It should be emphasized that EBV-associated disease seems to be a
      suitable disease for CBSCT, because all of the 4 patients who underwent CBSCT are
      still in CR.

PMID- 17176888
TI  - [Plasmodium vivax malaria with clinical presentation mimicking acute type
      idiopathic thrombocytopenic purpura].
AB  - Causes of thrombocytopenia are diverse, and infection with plasmodia often brings
      about thrombocytopenia. Japan is not an endemic area of malaria infection at
      present and most cases are travelers to endemic areas. In some cases, initial
      clinical diagnoses may not be correct because of a variety of symptoms, physical
      findings and laboratory abnormalities. A 67-year-old female, who had traveled to
      South American countries 2 months before the onset of the disease, presented with
      a case of vivax malaria. Because of the patient's high fever, profound
      thrombocytopenia (1.5 x 10(4)/microl), and elevated platelet-associated IgG on
      admission, our initial diagnosis was acute type idiopathic thrombocytopenic
      purpura (ITP). However, we recognized her tertian fever and plasmodial vivax in
      erythrocytes 4 days later. She responded promptly to anti-parasitic therapy after
      diagnosis of malaria and her laboratory data also improved. Travel history is
      indicative of malaria infection in some cases with thrombocytopenia mimicking
      acute ITP.

PMID- 17176889
TI  - [Peripheral T-cell lymphoma presenting with eosinophilia due to interleukin-5
      produced by lymphoma cells].
AB  - A 72-year-old male was admitted to our hospital to determine the cause of neck
      lymphadenopathies. He was diagnosed pathologically by a lymph node biopsy as
      having peripheral T-cell lymphoma (PTCL). He also had developed eosinophilia and
      his serum concentration of Interleukin-5 (IL-5) was extremely high.
      Immunostaining of a resected lymph node revealed that there were lymphoma cells
      which were stained with anti-IL-5 antibody. After 2 courses of CHOP therapy, the
      lymphadenopathies and eosinophilia disappeared and the concentration of serum IL
      5 was normalized. It was suggested that IL-5 produced by lymphoma cells had
      induced his eosinophilia.

PMID- 17176890
TI  - [Cord blood transplantation after successful treatment of brain abscess caused by
      Bacillus cereus in a patient with acute myeloid leukemia].
AB  - Central nervous system infection caused by Bacillus cereus is a rare condition,
      which often progresses rapidly and is fatal in immunocompromised patients. A 54
      year-old woman with acute myelogenous leukemia fell into a coma with high fever
      during severe neutropenia while undergoing chemotherapy. A blood culture
      demonstrated the presence of B. cereus and magnetic resonance imaging showed
      multiple abnormal lesions in her brain. The patient was treated with meropenem
      and vancomycin, and recovered from the coma in a week. Antibiotic therapy was
      administered for seven weeks, and then she underwent cord blood transplantation
      for refractory acute myelogenous leukemia with successful engraftment without
      exacerbation of the brain abscess. This case demonstrates that brain abscess
      caused by B. cereus can be treated without surgical treatment.

PMID- 17176891
TI  - [Cryotherapy is useful and safe in the prevention of oral mucositis after high
      dose melphalan (L-PAM)].
AB  - We prospectively assessed the effectiveness of cryotherapy after high-dose L-PAM
      to prevent oral mucositis. Cryotherapy with ice tips was commenced 15 minutes
      before L-PAM administration, and continued until the end of administration.
      Twenty-six patients were enrolled in this study. Thirteen patients with myeloma
      were treated with 200 mg/m2 L-PAM followed by autologous peripheral blood stem
      cell transplantation, and 13 patients (4 AML, 4 MDS, 2 ALL, 2 lymphoma and 1 CML)
      were treated with 140 mg/m2 L-PAM followed by allogeneic stem cell
      transplantation. Grade 1 mucositis occurred in four of 13 patients (31%) with 200
      mg/m2 L-PAM, and 2 of 13 patients (16%) with 140 mg/m2 L-PAM. Only one patient
      had grade 2 mucositis, and no grade 3 mucositis were observed. The procedure was
      well tolerated in all patients. These data suggest that cryotherapy is effective
      to minimize L-PAM-induced oral mucositis.

PMID- 17176892
TI  - [Expression and function of prostanoid receptors].

PMID- 17176893
TI  - [Metabolism and cellular functions of poly(ADP-ribose)].

PMID- 17176894
TI  - [Observation of sperm-egg interaction through gene-manipulated animals].

PMID- 17176895
TI  - [Wnt-induced polarity formation in early C. elegans embryo].

PMID- 17176896
TI  - [Regulation of exocytosis by myosin-V, the intracellular local transporting
      molecular motor].

PMID- 17176897
TI  - [Acidic phospholipids as cryptic leading players in NADPH oxidase activation].

PMID- 17176898
TI  - [Yeast prion as a model of prion concept].

PMID- 17176899
TI  - [Production of monoclonal antibodies by using lymphocytes from enlarged iliac
      lymph nodes of mice immunized intramuscularly at the tail base].

PMID- 17176900
TI  - [Hantavirus in Zulia state?].
AB  - During the last years, there has been a worldwide rise in the number of
      infectious diseases caused by newly discovered agents, in some cases and in
      others, by variants known as emergent or reemergent pathogens. The analysis of
      the nucleotide sequences of four RNA-positive hantaviruses (S. altoni) suggests
      that the Cano Delgadito virus is widely distributed in the Venezuelan plains. A
      similar distribution has been found for some isolates and strains of a novel
      hantavirus (proposed name "Mamporal"), which is phylogenetically very closely
      related to the pulmonary syndrome--causing hantaviruses of southern South
      America. There have not been clinical cases described or isolates of these
      viruses in Zulia state, Venezuela. However, some positive serological evidences
      suggest that their presence in this geographic area should be taken into
      consideration and further investigated.

PMID- 17176901
TI  - [Effect of changes in airway pressure and the inspiratory volume on the fluid
      filtration rate and pulmonary artery pressure in isolated rabbit lungs perfused
      with blood and acellular solution].
AB  - It has been reported that ventilation with large tidal volumes causes pulmonary
      edema in rats by the stimulation and release of proinflammatory mediators. Our
      objective was to determine the level at which volutrauma induced by changes in
      Airway Pressure (PAW) and Inspiratory Volume (VI) produce significant changes on
      the Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP) in lungs
      perfused with blood (cellular groups) or with a buffer-albumin solution
      (acellular groups), with a Positive End Expiratory Pressure (PEEP) 0 or 2 cmH2O
      and to study the effect of a vasodilator with antiinflammatory properties
      (fenoterol) in blood-perfused groups. Three experimental groups were used: the
      cellular groups studied the effect of increased PAW and IV in isolated lungs
      perfused with blood and PEEP 0 and 2; the acellular groups studied the increased
      PAW and IV in isolated lungs perfused with a buffer-albumin solution and PEEP 0
      and 2; The fenoterol group studied the effect of increased PAW and IV in isolated
      lungs perfused with blood + fenoterol and PEEP 2. The results show that an
      increase of FFR is produced earlier in acellular groups than in cellular ones and
      that the damage in cellular groups is microscopically and macroscopically
      inferior when compared to acellular groups. Fenoterol did not inhibit edema
      formation, and that PEEP 2, both in the cellular and the acellular groups, has a
      protective effect. We propose the possible existence of mediators with protective
      effects against the formation of pulmonary edema in the blood. These data suggest
      that volutrauma induced pulmonary edema has a predominantly traumatic origin when
      the lungs are perfused with blood.

PMID- 17176902
TI  - [Use of polymerase chain reaction for the diagnosis of central nervous system
      infections].
AB  - In the present work, the polymerase chain reaction (PCR) assay and his variants
      RT-PCR and Multiplex PCR were applied for the detection of specific sequences of
      Enterovirus, Human Herpes viruses (Herpes simple virus, Human Herpes virus type
      6, Cytomegalovirus, Epstein Barr virus, and Varicella Zoster), Human
      Immunodeficiency virus, Toxoplasma gondii, Mycobacterium tuberculosis and
      Mycoplasma pneumoniae in patients' cohorts grouped by medical suspicion of
      meningoencephalitis. Of 326 samples of processed cerebrospinal fluid (CSF), 93
      samples (28.5%) were positive for the different infectious agents. In the group
      of patients with clinical diagnosis of viral meningoencephalitis (n=212), there
      was obtained a whole of 73 positive samples (34.4%), of which 37 patients were
      positive to Enterovirus (50.7%), 19 were positive to VHS (26%) and 10 patients
      (13.7%) were positive to CMV. Other viral agents as VZV, EBV and HVH6 were
      detected in minor frequency. The 114 remaining samples were analyzed applying
      specific PCR to each pathogen for strict medical indication, being able to detect
      the presence of Human Immunodeficiency Virus (40%), Mycoplasma pneumoniae (40%),
      Toxoplasma gondii (14%) and Mycobacterium tuberculosis (12%) in CSF samples. The
      results obtained in this study demonstrate the convenience of the application of
      the molecular assays in the laboratory diagnosis of the meningoencefalitis of
      different etiology. Besides this, it is also a very valuable tool for the
      clinical management of the patients and for the execution of the epidemiological
      studies.

PMID- 17176904
TI  - Immunophenotype characteristics of peripheral blood mononuclear leukocytes of
      chronic idiopathic urticaria patients.
AB  - The pathogenesis of chronic idiopathic urticaria (CIU) is not completely
      understood although autoimmunity has been proposed. The aim of the study was to
      assess the expression of different leukocyte antigens, by flow cytometry,
      assaying total blood of 29 patients with CIU and of 20 sex and age matched
      controls. Moreover, we assessed soluble CD154 a marker of immune cell activation,
      predominantly memory T cells. When patients were divided depending an their
      response to the autologous serum skin test (ASST), three different groups were
      encountered: group 1 (n=11): with negative ASST-, group 2 (n=11): positive ASST
      (ASST+) with normal lymphocyte counts and group 3 (n=7): ASST+ with low
      lymphocyte counts (< 1500 cells/mm3). A significant increase in CD19+ percentage
      and not in the absolute count (P < 0.05) was observed in group 1 as compared to
      controls and to the other groups. In contrast, CD30+, CD45RO+ and CD4+/CD45RO+
      percentages and biologically active soluble CD154 levels were significantly
      higher (P < 0.05) in group 3 as compared to group 1 or to controls. In ASST
      positive groups, CD45RO+ and CD4+/CD45RO+ positiveness correlates with wheal
      diameter. In conclusion, memory cells may play a role in these different types of
      patients and in understanding CIU pathogenesis.

PMID- 17176903
TI  - [Serum levels of Zn in children with different degress of nutritional
      deficiency].
AB  - The importance of Zinc (Zn) as a necessary oligoclement for human nutrition
      begins in the first three decades of life. At the moment, the role that Zn plays
      in the infantile nutrition is very well-known, acquiring a special connotation in
      children with proteic-energetics malnutrition (PEM). In this study the daily
      ingestion and the serum measuremets of Zn were determined in 64 undernourished
      children (light, mild and severe) and in 25 eutrophic children with ages between
      1 to 5 years, belonging to families of the strata IV and V according to the
      Graffar scale corrected by age. The results of the serum values of Zn were for
      the light undernourished of 39.73 +/- 14.97 microg/dL (30.38 microg/dL-44.56
      microg/dL), for the mild undernourished of 35.07 +/- 28.13 microg/dL (27.76
      microg/dL-65.80 microg/dL) and for the severe undernourished of 15.48 +/- 10.44
      microg/dL (5.57 microg/dL-28.56 microg/dL), which were diminished in relation
      with the control group, 76.71 +/- 33.29 microg/dL (45.75 microg/dL - 78.27
      microg/dL) with p < 0.0001. Equally, there were significant differences (p <
      0.001) among the group of severe undernourished with the light undernourished and
      normal subjects. In relation with the daily ingestion of Zn, a statistically
      significant difference was observed only (p < 0.001) in the severe
      undernourished, 1.87 +/- 0.54 mg/dia (1.20 mg/dia-2.87 mg/dia) when comparing
      them with the light undernourished, 5.48 +/- 0.98 mg/dia (3.50 mg/dia-7.87
      mg/dia), the mild undernourished, 4.99 +/- 1.24 mg/dia (4.10 mg/dia-11.42 mg/dia)
      ) and the normal subjects, 6.22 +/- 0.98 mg/dia (4.8 mg/dia-8.02 mg/dia). There
      was a positive correlation between ingestion and seric values of Zn when the 3
      undernourished groups were studied. These results allow to conclude that both the
      seric values of Zn and its ingestion show modifications in relation with the
      degree of nutritional deficiency.

PMID- 17176905
TI  - [Importance of E-cadherin; expression in the inmunohistochemical diagnosis of
      breast cancer].
AB  - It has been propossed that 50% of lobular carcinomas (LC) may change their
      phenotype to ductal carcinoma (DC) in 20 years. Since the prognosis and treatment
      of both breast carcinomas is different, it seems to be important; investigate
      through immunohistochemistry the loss of E-cadherin expression. E-cadherin
      expression was investigated in 90 cases with diagnosis or histological appearance
      of LC or mixed carcinomas (MxC), and in 30 DC selected among 385 cases received
      during year 2005 to be examined for immunohistochemical diagnosis. In 349 cases a
      diagnosis of DC was made. In the 90 cases selected to investigate EC the
      diagnosis of LC and MxC was performed in 36 cases, and among them, the
      histological diagnosis on 44.4% was modified. In 7 cases the diagnosis of LC was
      changed to DC, and 10 cases with diagnosis of MxC were considered to be DC. In 8
      cases with diagnosis of DC and/or MxC the final diagnosis was that of LC. The
      histological diagnosis of CL is not always easily made and there are cases of DC
      with the appearance of LC, and cases of LC and MxC which may simulate to be DC.
      Diagnostic pitfalls in 44.4% of cases classified as LC and MxC after EC, were
      noted in our study. This percentage is close to the proposed 50% of cases of LC
      changing their phenotype to DC. The results with EC herein presented, suggested
      that diagnostic failures are due to the slight histological differences between
      both LC and DC. Recent evidences seems to indicate that there is a relationship
      between loss of EC and Tiroxine kynase receptors of the Epidermal Growth Factor
      related to migration and invasiveness of tumor cells. Immunohistochemical studies
      on the expression of EC in breast cancer is emphasized.

PMID- 17176906
TI  - [Ascaris lumbricoides: heterogeneity in ABO epithopes expression].
AB  - Ascaris lumbricoides and its hosts can present the same ABO System epithopes. The
      aim was to study ABO epithopes expression in A. lumbricoides by Inhibition
      Agglutination Test using different monoclonal antibodies and policlonal sera. We
      worked with 27 parasite extracts (14 extracts from A Group patients, 2 AB Group
      1, B Group and 10 from unknown ABO Group patients). Inhibition Agglutination Test
      was made facing the extracts from A, AB and unknown ABO Group patients against
      monoclonal antibodies and policlonal serum of A specificity and the extracts from
      B, AB and unknown ABO Group patients against monoclonal antibodies and policlonal
      serum of B specificity. The Semiquantitative Test was made with the extracts
      which inhibited the agglutination of any antibody. The 50% of the parasite
      extracts faced against A specificity antibodies and the 46% of the parasite
      extracts faced against B specificity antibodies significantly inhibited the
      agglutination in the Semiquantitative Test. No extract inhibited the totality of
      the antibodies. All the antibodies reacted with some extract, except one antibody
      of B specificity. The ABO activity in the extracts was independent of the
      antibody's immunoglobulin class, titre and concentration and it only was
      dependent on the antibody union with the epithope at which the antibody is
      directed. The heterogeneity in the ABO epithopes expression of A.lumbricoides
      might be involved in the escape of the host's immune response. The used
      Inhibition Tests are sensitive, simple, rapid and economic. We conclude that the
      use of different antibodies alows the best definition of the antigen-antibody
      specificity.

PMID- 17176907
TI  - [Molecular analysis of microdeletions of the Y chromosome in Venezuelan males
      with idiopathic infertility].
AB  - Today infertility is a major health problem affecting about 10-20% of couples. A
      male factor is assumed to be responsible in about 50% of the infertile couples.
      The origin of reduced testicular sperm function is unknown in about 60-70% of
      cases. There are several causes of male infertility such as varicocele, spermatic
      duct obstruction, and endocrine disorders. Micro-deletions in the Yq are known to
      represent the pathogenic mechanisms for infertile males. Three different non
      overlapping regions designated as AZFa, AZFb, and AZFc are located in interval 5
      6 of Yq, and are associated with impaired spermatogenesis in humans. To determine
      the prevalence of Y chromosomal microdeletions in Venezuelan males with
      idiopathic infertility, chromosomal, seminal, histological and molecular analyses
      were carried out in 29 Venezuelan males with idiopathic azoospermia or
      oligoospermia. Y-microdeletions analyses were performed using a multiplex
      polymerase chain reaction (PCR)-based technique with 22 sequences-tagged-sites
      (STSs). One of 29 patients (3.4%) had Yq microdeletions on AZFc. The frequency of
      AZF microdeletions in Venezuelan patients was similar to other populations with
      different ethnical or geographical origin.

PMID- 17176908
TI  - Behcet's disease and IgA nephropathy: report of this association in a patient
      from Brazil and literature review.
AB  - Behcet's disease (BD) is associated with renal involvement in about one-third of
      the cases and a variety of renal lesions have been reported. A 27-year-old man
      presented a history of recurrent oral and genital ulcers, associated with
      pseudofoliculitis and arthritis in his left knee. The first laboratory tests
      revealed: urea = 53mg/dL, creatinine = 1.8 mg/dL. The urinalysis showed
      leukocyturia. Initial treatment with ceftriaxone, thalidomide and prednisone was
      instituted. He became clinically stable, with normal renal function, but
      presenting hematuria and proteinuria. One year later the patient presented dark
      urine. The new laboratory tests showed urea=58 mg/dL, creatinine = 1.4 mg/dL, and
      mild proteinuria (500-1000 mg/24h). Two years later the proteinuria was 2230
      mg/day. The renal biopsy showed one glomerulus with severe glomerular sclerosis,
      mild tubular atrophy, mild interstitial fibrosis and thickening of arterial
      walls. Treatment with captopril was started to decrease proteinuria. Two years
      later, the patient presented creatinine = 1.7 mg/dL and proteinuria = 2509
      mg/day. A new renal biopsy evidenced proliferative crescentic glomerulonephritis,
      with diffuse granullary deposits of IgA, IgM and C3. It was instituted
      pulsotherapy with metilprednisolone, monthly endovenous cyclophosphamide and
      maintenance prednisone. The patient became clinically stable, with creatinine of
      1.3 mg/dL and proteinuria of 500 mg/day. BD could be one of the various causes of
      secondary IgA nephritis. It is important to periodically perform renal function
      evaluation in patients with BD, through urinalysis and measurement of serum
      creatinine and its clearance, in order to detect any abnormality and provide an
      early adequate treatment.

PMID- 17176909
TI  - [Multiple sclerosis in children: clarifying its place among the demyelinating
      spectrum].
AB  - Multiple sclerosis (MS) is an autoimmune disease caused by the destruction of the
      myelin layer and the nervous fibers, and secondary by a progressive neuronal
      damage. It is characterized by episodes of demyelination disseminated in time and
      space in different areas of the white matter of the CNS which includes
      periventricular region, spinal cord, brain stem, cerebellum and optical nerve.
      Due to the confusing differential diagnosis of MS in children with other
      demyelinating diseases such as ADEM, it is important to reach this diagnosis when
      there is proof of white matter lesions disseminated in time and space that cannot
      be explained by any other mechanisms or pathologies. The goal of this paper is to
      review the diagnostic parameters used for MS in the pediatric age, the dilemmas
      regarding the validity of diagnostic criteria, clinical manifestations,
      differentiation of other demyelinating diseases, and the diagnostic process. MS
      although infrequent, is a valid diagnosis among the spectrum of childhood
      inflammatory demyelinating diseases. The clinical presentation might be
      indistinguishable from a multifocal acute disseminated encephalopathy or could be
      presented with just focal signs. A reasonable clinical judgment and the practice
      of laboratory tests confirm or rule out the diagnosis. It is not possible to
      differentiate between ADEM and MS in a first episode, nor by the clinical, the
      CSF, neither the neuroimaging. There are still needed consensus criteria both
      clinical and laboratory test. There are many question still to be answered using
      prospective studies, and standardized clinical measures that will allow the
      delimitation of the demographic, neurological, and neuropsychological aspects of
      the MS and other form of acquired demyelinating diseases in children.

PMID- 17176910
TI  - A clinicopathologic study of thrombotic microangiopathy in the setting of IgA
      nephropathy.
AB  - BACKGROUND: IgA nephropathy is the most common glomerulonephritis in the world.
      Thrombotic microangiopathy occurs in a number of clinical settings, including but
      not limited to thrombotic thrombocytopenic purpura/hemolytic uremic syndrome,
      malignant hypertension, anti-phospholipid antibody syndrome and radiation
      nephropathy. Renovascular complications, such as thrombotic microangiopathy, in
      the setting of IgA nephropathy may be overlooked and their significance as a
      concomitant histologic finding is unclear. METHODS: We conducted a
      clinicopathologic study to understand the possible relationship between IgA
      nephropathy and a concurrent thrombotic microangiopathy injury process. We
      identified 10 patients with an established diagnosis of IgA nephropathy and
      concurrent findings of thrombotic microangiopathy based on their renal biopsies.
      RESULTS: Six patients presented with malignant hypertension, while three others
      had severe hypertension (> or = 100 mmHg, diastolic). Five patients had nephrotic
      range proteinuria. Seven patients had occasional arteriolar thrombi identified by
      light microscopy and prominent glomerular subendothelial space widening by
      electron microscopy, while three patients demonstrated only ultrastructural
      features of thrombotic microangiopathy. Other possible etiologic causes of
      thrombotic microangiopathy were not identified with the available clinical
      information. CONCLUSION: Our study suggests that a thrombotic microangiopathy
      injury, when present, is usually found in advanced stages of IgA nephropathy and
      can be associated with severe proteinuria. Although other possible causes of
      thrombotic microangiopathy, such as anti-phospholipid antibody syndrome, were
      excluded in only two patients, the thrombotic microangiopathy injury process may
      be a cause or a consequence of the severe hypertension encountered in most of the
      patients which, in turn, may be a consequence of the disease progression of IgA
      nephropathy.

PMID- 17176911
TI  - Protective effect of radical scavenger edaravone against puromycin nephrosis.
AB  - AIM: Recent studies have indicated that reactive oxygen species (ROS) play a role
      in the pathogenesis of glomerular injury leading to proteinuria in nephrotic
      syndrome. In the present investigation, we examined the effects of the radical
      scavenger edaravone administered at various time points to rats with puromycin
      nephrosis. MATERIALS AND METHODS: 35 Wistar rats were divided into five groups:
      treatment with puromycin aminonucleoside (PAN) alone, treatment with PAN followed
      by edaravone in the early period, treatment with PAN followed by edaravone
      administration in the late period, treatment with PAN and administration of
      edaravone for the whole experimental period, and untreated controls. On Days 3, 6
      and 9, urinary protein excretion was measured. The levels of glomerular
      thiobarbituric acid-reactive substance (TBArs) were determined in all animals on
      Day 10. RESULTS: On Day 9, rats that had been administered edaravone showed
      reduced urinary protein excretion and reduced glomerular TBArs. In particular,
      edaravone administration in the late period, during which proteinuria was most
      acute, had the effect of reducing the severity of proteinuria. Glomerular TBArs
      were suppressed to the control level. Our results indicate that edaravone exerts
      a protective effect in the acute phase of PAN nephrosis when administered as
      antioxidant therapy at the onset of proteinuria. CONCLUSIONS: Edaravone can
      ameliorate urinary protein excretion after the onset of proteinuria in nephrotic
      syndrome.

PMID- 17176912
TI  - Influence of mineral metabolism parameters on pulse pressure in healthy subjects.
AB  - BACKGROUND: The role of mineral metabolism in cardiovascular pathologies has been
      studied almost exclusively in chronic kidney disease patients. There are no
      studies that relate mineral metabolism to pulse pressure in healthy populations.
      METHODS: 692 subjects were initially selected. After applying clinical exclusion
      criteria, 659 subjects were recruited. Creatinine clearance was then calculated
      to detect subjects with occult chronic kidney disease. Statistical analysis was
      applied to the remaining population after excluding subjects with occult chronic
      kidney disease (n = 466). Pulse pressure, creatinine clearance, calcium,
      phosphorus, intact parathormone, 25-hydroxivitamin D3 and Bsm I genotype of the
      vitamin D receptor were determined. Means and frequencies were compared by ANOVA
      and Chi-square, respectively. Multivariate analysis was applied to the whole
      population and then to Caucasians, Sub-Saharans, Caucasian men and Caucasian
      women separately. Pulse pressure (PP) was the dependent variable, and adjustments
      were made for clinical and laboratory data. RESULTS: The prevalence of occult
      chronic kidney disease was 32%. In subjects without kidney disease, phosphorus
      and vitamin D were independent predictors of elevated PP in Caucasian males
      whereas Bsm I genotype of the vitamin D was an independent predictor of elevated
      PP in the Caucasian population in both genders. No covariable showed relationship
      with PP in Sub-Saharan subjects. CONCLUSION: Mineral metabolism influences pulse
      pressure in Caucasian men.

PMID- 17176913
TI  - Plasma pentosidine and total homocysteine levels in relation to change in common
      carotid intima-media area in the first year of dialysis therapy.
AB  - BACKGROUND: Homocysteine and advanced glycation end-products (AGEs), which
      accumulate in chronic kidney disease (CKD), are recently proposed cardiovascular
      risk factors. In this study, we evaluated the association between changes in
      calculated intima media (cIM) area of the common carotid artery during the first
      year of dialysis therapy and plasma total homocysteine (tHcy) level as well as
      circulating AGEs such as plasma pentosidine level. METHODS: We studied 63 CKD
      patients (38 males) aged 52 +/- 12 years at a time-point close to start of
      dialysis treatment and after 12 months of dialysis treatment (41 on peritoneal
      and 22 on hemodialysis). The tHcy and plasma pentosidine levels were measured by
      HPLC. Change in cIM area was evaluated by non-invasive B mode ultrasonography.
      Malnutrition was assessed by subjective global assessment (SGA). RESULTS: At
      basal, 70% of the patients had carotid plaques, 32% had symptomatic CVD, 38% had
      malnutrition, 30% had inflammation (CRP > or = 1 mg/dl) and 23% had diabetes
      mellitus, respectively. At baseline, the mean plasma pentosidine levels were
      similar in the patients with and without carotid plaques (36 +/- 21 vs 36 +/- 19
      pmol/mg albumin, respectively), whereas the median plasma tHcy was significantly
      lower in the patients with carotid plaques than in the patients without carotid
      plaques (32 +/- 21 vs 52 +/- 42 pmol/l, p < 0.01, respectively). The prevalence
      of hyperhomocysteinemia (tHcy level > 13.7 micromol/l) was 95%. In univariate
      analysis, the change in cIM area during the first year of dialysis was
      significantly correlated with basal plasma pentosidine level (p = 0.31, p =
      0.01), but not with basal tHcy (p = -0.11). However, neither pentosidine nor tHcy
      levels were correlated with cIM area at basal or at 12 months. In a stepwise
      multiple regression model, age and plasma pentosidine content, but not the tHcy
      level, associated with changes in the cIM area. CONCLUSION: Progression of
      atherosclerosis, as indicated by changes in carotid intima-media area during the
      course of dialysis treatment, was associated with pentosidine, but not with tHcy,
      levels at baseline in these CKD patients. This suggests that the accumulation of
      AGEs in CKD patients may have a role in the pathogenesis of CVD in these
      patients. Since almost all CKD patients have hyperhomocysteinemia, this finding,
      however, does not exclude a role ofhomocysteine as a risk factor for CVD in CKD
      patients.

PMID- 17176914
TI  - Effect of different dialyzer membranes on cutaneous microcirculation during
      hemodialysis.
AB  - AIM: Biocompatibility profiles of synthetic membranes may vary. In this
      prospective crossover study, we examined the effect of various membranes on
      cutaneous microcirculation during HD. SUBJECTS AND METHODS: 11 HD patients
      without cardiovascular complications were enrolled in this study. They were
      dialyzed using three types of membrane in a randomized order: ethylene-vinyl
      alcohol copolymer (EVAL), vitamin E-bonded cellulose (VE-C) and polysulfone (PS).
      The transcutaneous oxygen tension (TcPO2) was examined on the dorsum of foot to
      assess the cutaneous microcirculation. Serum biochemical parameters were also
      measured. RESULTS: The TcPO2 as a percentage of the predialysis level decreased
      from the beginning of HD, and significant differences were observed after 15 min
      of HD between EVAL and the other 2 membranes (98 +/- 6% (mean +/- SD) for EVAL
      versus 89 +/- 7% for VE-C (p < 0.01) and 88 +/- 10% for PS (p < 0.01)).
      Furthermore, there were significant differences at 30 and 60 min between EVAL and
      PS (30 min: 93 +/- 9% for EVAL versus 85 +/- 7% for PS (p < 0.05); 60 min: 92 +/-
      10% for EVAL versus 79 +/- 10% for PS (p < 0.01)). The serum level of
      thiobarbituric acid reactants (TBARs), a marker of lipid peroxidation, increased
      significantly at the end of HD relative to that at the beginning of HD when using
      a PS membrane (from 1.9 +/- 0.5 to 2.1 +/- 0.5 nmol/ml, p < 0.05). CONCLUSION:
      Our results indicate that an EVAL membrane is superior to PS and VE-C membranes
      in terms of its smaller influence on cutaneous microcirculation. The repeated
      occurrence of microcirculatory disturbance during HD sessions may cause chronic
      endothelial dysfunction and even cardiovascular complications in HD patients.

PMID- 17176915
TI  - Effects of an increase in time vs. frequency on cardiovascular parameters in
      chronic hemodialysis patients.
AB  - Cardiovascular mortality is still high and many risk factors are inadequately
      controlled in patients on conventional chronic hemodialysis. Recent studies on
      intensified treatment schedules by either increasing length or frequency of
      dialysis sessions have shown promising results with better control of blood
      pressure, reduction of left ventricular hypertrophy and easier control of
      calcium/phosphate metabolism. AIM: The present observational study compared the
      effect of different forms of "intensified dialysis treatment" i.e. either long
      nightly intermittent (LNHD, 3 x 7.5 - 8 h) or short daily dialysis sessions (DHD,
      6 x 2.5 - 3 h) on cardiovascular parameters, phosphate and anemia control in
      comparison to standard treatment schedules (SHD, 3 x 4 - 5 h). METHODS: All
      patients stable on hemodialysis between 18 and 80 years of age and with either
      uncontrolled hypertension and/or left ventricular hypertrophy and/or frequent
      intradialytic hypotension, were asked to participate in intensified dialysis
      therapy by either LNHD or DHD. Patients not willing to change their dialysis
      regime were asked to participate as control group (SHD). Primary end point was 24
      h ambulatory blood pressure, secondary end points were predialysis blood
      pressure, left ventricular mass index (LVMI) and fractional shortening (FS),
      control of calcium, phosphate and anemia. Patients were followed up for 1 year.
      RESULTS: 17 patients opted for LNHD, 8 for DHD, 19 patients served as control
      group. After 1 year of treatment 24-h blood pressure was unchanged in all groups.
      Predialysis systolic blood pressure decreased in LNHD and DHD, but increased in
      SHD. Mean LVMI decreased in all treatment groups (DHD -20.1 +/- 24.0%, SHD -13.6
      +/- 33.4%, LNHD -6.1 +/- 32.2%). The mean number of antihypertensive tablets/day
      was reduced in DHD by 3.3 tablet units, in LNHD by 1.2 tablet units, but
      increased in SHD patients. FS improved in patients on LNHD and DHD, but decreased
      in patients on SHD. Regression of LVMI was independent of dry weight which was
      unchanged in LNHD and SHD but increased in DHD. In contrast to SHD, phosphate
      control and Ca x P product improved in DHD and LNHD with less phosphate binding
      tablets. Intact PTH did not change in SHD, but decreased in DHD and LNHD.
      Hemoglobin increased in groups on intensified treatments, but fell in SHD. EPO
      resistance index fell in LNHD, but increased in DHD and SHD. CONCLUSION: While
      reduction in 24-h blood pressure was not achieved by intensified dialysis, both
      schedules showed favourable effects on LVMI and FS with less antihypertensive
      medication. This was independent of reduction in dry weight. These effects were
      more pronounced in DHD patients. In contrast, in SHD patients, stable 24-h blood
      pressure and reduction in LVMI were achieved on the expense of an increasing
      amount of antihypertensive medication and with worsening of FS.

PMID- 17176916
TI  - Restless legs syndrome in hemodialysis patients: health-related quality of life
      and laboratory data analysis.
AB  - AIMS: To compare clinical data, sleep quality and health-related quality of life
      (HRQOL) with and without RLS in HD patients. MATERIALS AND METHODS: The
      international RLS study group diagnosis questionnaire was completed by 228 HD
      patients. The Pittsburg Sleep Quality Index (PSQI) for the evaluation of sleep
      quality and the Kidney Disease Quality of Life (KDQOL-SF) for the analysis of
      HRQOL were also used. RESULTS: 53 (23%) patients were diagnosed as RLS. Age and
      age at the initiation of HD were significantly younger in the RLS group. Serum
      calcium concentration (Ca) was significantly higher in the RLS group. Sleep
      quality evaluated by PSQI was significantly lower in the RLS group. In SF-36
      domains of KDQOL-SF, bodily pain, general health perceptions, vitality, role
      functioning emotional, mental health and mental component score were
      significantly lower in the RLS group. In kidney targeted scales of KDQOL-SF,
      symptoms/problems, burden of kidney disease, cognitive function, quality of
      social interaction, sleep and patient satisfaction were significantly lower in
      the RLS group. CONCLUSION: High Ca was possibly connected to the pathophysiology
      of RLS which impaired sleep quality as well as HRQOL including mental health and
      many kidney disease related scales.

PMID- 17176917
TI  - Cytoplasmic antineutrophil cytoplasmic antibody positive pauci-immune
      glomerulonephritis associated with infectious endocarditis.
AB  - Renal deterioration often occurs in cases of infectious endocarditis (IE), but,
      IE- associated nephritis with rapidly progressive glomerulonephritis (RPGN) is
      rare. Patients with severe infection (e.g., IE) sometimes show positivity for
      cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA). Therefore, diagnosis
      and treatment are very difficult in cases of RPGN with IE and positivity for C
      ANCA. Such cases are rare, only 12 have been reported in the English literature.
      Herein, we describe the case of a 50-year-old man who presented with RPGN with IE
      and tested positively for C-ANCA. He was referred to our hospital because of leg
      edema, purpura and renal dysfunction. Laboratory tests revealed serum creatinine
      elevation and positivity for C-ANCA and proteinase 3-specific (PR3)-ANCA. RPGN
      and acute renal failure were diagnosed. Hemodialysis and steroid therapy were
      started. Streptococcus oralis was isolated by blood culture. Transthoracic
      echocardiography revealed grade III mitral valve insufficiency with two
      vegetations. Therefore, IE was diagnosed. The steroid therapy was stopped, and
      antibiotic therapy was begun. Because there was no improvement, surgical therapy
      was performed. The operation was successful, but the patient died of brain
      hemorrhage. Our experience in this case indicates C/PR3-ANCA positive RPGN must
      be ruled out in patients with infectious disease, particularly IE, together with
      renal symptoms, and renal biopsy should be performed.

PMID- 17176919
TI  - Minimal change nephrotic syndrome in association with strongyloidiasis.
AB  - Although parasitic infections have been known to be associated with immune
      complex-mediated glomerular lesions, strongyloidiasis-related glomerulopathy has
      not been well documented. We report a patient with delayed-recognized
      disseminated strongyloidiasis who developed nephrotic syndrome 3 months after the
      beginning of the manifestations related to strongyloidiasis. A kidney biopsy
      showed minimal change disease. We treated strongyloidiasis and hesitated to give
      steroid therapy for the treatment of minimal change nephrotic syndrome (MCNS)
      because of the risk of aggravation of Strongyloides stercoralis infection.
      Surprisingly, resolution of heavy proteinuria occurred after anthelmintic therapy
      with ivermectin. This case suggests a possible causal relationship between S.
      stercoralis infection and MCNS. In addition, a review of another 4 cases
      previously reported in the literature demonstrates the importance of detecting
      underlying S. stercoralis infection in patients with nephrotic syndrome since
      steroid therapy can cause hyperinfection or disseminated strongyloidiasis, and
      which may lead to fatal outcome.

PMID- 17176918
TI  - Acute immuno-allergic interstitial nephritis caused by fluindione.
AB  - Fluindione is a vitamin K antagonist that is commonly prescribed for the
      treatment of cardiovascular disease and venous thromboembolism in France.
      Bleeding is the most common side effect of fluindione, whereas hypersensitivity
      reactions are rare. We describe here a patient with acute immuno-allergic
      interstitial nephritis caused by fluindione. Initial symptoms included fever,
      eosinophilia, low albuminuria, microscopic hematuria, eosinophiluria and acute
      renal failure. Kidney biopsy showed severe interstitial nephritis with
      interstitial edema, inflammatory infiltrates and tubulorrhexis. Fluindione
      withdrawal and corticosteroid treatment resulted in rapid recovery of renal
      function. A review of the literature revealed a very low incidence of fluindione
      induced interstitial nephritis, with variable renal and extra-renal signs. Early
      recognition of this rare complication may prevent the development of severe
      chronic renal injury.

PMID- 17176920
TI  - Acute renal failure associated with use of inhaled tobramycin for treatment of
      chronic airway colonization with Pseudomonas aeruginosa.
AB  - Aminoglycoside nephrotoxicity is a well-known clinical entity that complicates
      the course of infectious diseases treated under this antibiotic regime. Recently,
      a new administration form of tobramycin, inhaled tobramycin (TOBI), has been
      approved to improve the antibacterial activity and reduce nephrotoxicity. We
      describe the clinical case of a 73-year-old woman with chronic-obstructive
      pulmonary disease (COPD) who developed acute renal failure (ARF) after using
      TOBI. Clinical presentation and biochemical parameters were compatible with
      aminoglycoside-induced renal failure. Based on the clinical findings presented
      here, a surveillance program should be established to monitor the presence of
      factors predisposing to renal failure, and to measure serum levels of tobramycin.

PMID- 17176921
TI  - Acute renal failure after a holiday in the tropics.
AB  - A 20-year-old, previously healthy woman, presented with high fever, headache and
      myalgia 3 days after her return from a holiday in Southeast Asia. Laboratory data
      on admission demonstrated a pronounced increase in plasma creatinine, marked
      thrombocytopenia and moderately elevated liver aminotransferases. After having
      ruled out malaria, dengue fever was primarily suspected and supportive
      intravenous fluid therapy was initiated. Still, 1 day after admission, platelet
      counts dropped even further and she became anuric although she did not appear
      hypovolemic. On day 2 after admission, urine production commenced spontaneously
      and the patient slowly recovered. All laboratory test results had returned to
      normal approximately 2 months later. Serological analysis for dengue fever was
      negative. It turned out that the patient had been trekking in the jungle while in
      Thailand and we, therefore, analyzed serology for Leptospira spirochetes which
      was clearly positive. The patient was diagnosed with leptospirosis which is a
      serious condition associated with a high mortality when complicated by acute
      renal failure. Differential diagnoses in patients with acute renal failure and
      tropical infections are reviewed. The importance of early recognition of
      leptospirosis, and prompt treatment with antibiotics in suspected cases, is
      emphasized.

PMID- 17176923
TI  - Idiopathic retroperitoneal fibrosis associated with Hashimoto's thyroiditis: a
      long-term follow-up.

PMID- 17176922
TI  - Dermatopathic lymphadenopathy: a differential diagnosis of enlarged lymph nodes
      in uremic pruritus.
AB  - BACKGROUND: In end-stage renal disease patients, the incidence of both infections
      and malignancies is increased leading to a higher incidence of peripheral
      lymphadenopathy. In the present work we describe a rare but probably
      underdiagnosed cause for enlarged lymph nodes in uremic patients. PATIENT: A 43
      year-old male patient was admitted to our hospital with inguinal lymphadenopathy
      and pruritus. He turned out to be uremic due to focal segmental
      glomerulosclerosis (creatinine 4.5 mg/dl, MDRD creatinine clearance 12 ml/min).
      FINDINGS: Sonography revealed enlarged lymph nodes (up to 4 cm) with intact
      corticohilar border differentiation. After extirpation of an inguinal lymph node,
      histological examination established the diagnosis of dermatopathic
      lymphadenopathy. T cell lymphoma was excluded by PCR for T cell receptor-gamma
      rearrangements and subsequent GeneScan analysis. Intravenous fluid
      supplementation with subsequent decline of creatinine, UVB treatment, clemastine,
      and topical use of emollients led to a relief of the uremic pruritus and the
      lymph nodes' size normalized within 8 weeks. CONCLUSION: Dermatopathic
      lymphadenopathy refers to the reactive condition seen in lymph nodes that drain
      areas with disruption of the skin integrity, e.g. due to scratch marks. The
      present case report describes dermatopathic lymphadenopathy as a harmless cause
      of enlarged lymph nodes in uremic pruritus for the first time. This entity should
      be considered in the differential diagnosis of peripheral lymphadenopathy of
      unknown origin in patients with renal failure.

PMID- 17176924
TI  - [Aortic valve insufficiency].

PMID- 17176925
TI  - [What is your diagnosis? Acute gout attack].

PMID- 17176926
TI  - [Acute liver failure--medical viewpoints].
AB  - Acute liver failure is a rare disease that can cause death in the majority of
      untreated cases. Sudden loss of liver function in the absence of a preexisting
      liver disease is considered the true form and has to be distinguished from
      impaired function following exacerbation of an underlying liver disease (acute or
      chronic failure). Common causes include acute viral hepatitis, drug induced liver
      injury (DILI) and toxins. The loss of the excretory and synthetic function of the
      liver marks the clinical presentation and results in icterus, coagulopathy and
      encephalopathy. Additionally impairment of renal function and sepsis occur and
      contribute to the high mortality of this disease. The activation of cell death
      mechanisms (apoptosis) leading to a reductio of viable, functional liver tissue
      is considered to be an important pathophysiologic mechanism. Curative therapy of
      this disease includes liver transplantation that has been performed in Germany
      for the first time in 1969. In the year 2004 a total of 91 liver transplantation
      were performed for acute liver failure (10.3% of all transplants) in German
      transplant centers.

PMID- 17176927
TI  - [Acute liver failure--surgical approach].
AB  - Emergency liver transplantation is the only therapy of proven benefit for
      patients suffering from acute liver failure. The decision-making for
      transplantation mostly relies on clinical experience. The positive predictive
      value of prognostic scoring systems is reliable whereas the negative predictive
      value reaches only 60%. Due to a high postoperative mortality of 20-30%, the
      overall results after liver transplantation for acute liver failure are inferior
      to those obtained after transplantation for chronic liver diseases. The most
      important prognostic parameters are the severity of multi organ failures and the
      degree of encephalopathy prior to transplantation. However, long-term survival
      thereafter is mostly excellent.

PMID- 17176928
TI  - [Fulminant pancreatitis--internal point of view].
AB  - In acute pancreatitis pancreatic necrosis and involvement of different organ
      systems determine clinical course and severity. There is no method to predict the
      outcome of acute pancreatitis at the beginning of the disease. If there is
      evidence for severe pancreatitis, an immediate intensive care of all organ
      systems is needed, to avoid complications. Besides clinical signs, serum CRP is
      the most valuable parameter to define severity. According to present knowledge, a
      CT scan is only needed in sepsis or multiorgan failure. Non-invasive ventilation
      should be started early in case of hypoxia. Up to now, no general benefit was
      detected for antibiotic prophylaxis or enteral nutrition.

PMID- 17176929
TI  - [Fulminant pancreatitis--surgical point of view].
AB  - Today, treatment of acute pancreatitis is mainly conservative and surgery is on
      the retreat. Infection of pancreatic necrosis is still the main risk factor of
      morbidity and mortality in the course of necrotizing disease. A prophylactic
      treatment with antibiotics can reduce both infectious complications and
      mortality. Thus, antibiotics should be administered in severe pancreatitis. If
      pancreatic infection is suspected, fine needle aspiration should be performed.
      Today, infected pancreatic necrosis is a well accepted indication for surgery.
      Aim of the surgical procedure is to remove the septic focus by debridement of the
      infected pancreatic and peripancreatic necrosis. The optimal timepoint for the
      surgical intervention is the 3rd to 4th week after onset of the disease. At that
      time, necrotic tissue is well demarcated. Therefore bleeding complications and
      removal of vital tissue can be avoided. Today, surgical procedures should combine
      the necrosectomy with a postoperative method to continuously remove necrosis and
      debris. This is the case with the following two techniques, the postoperative
      continuous lavage and the closed packing. In contrast, sterile necrosis is
      usually treated conservatively. Fulminant acute pancreatitis is a rare subgroup
      of acute pancreatitis, characterized by a rapidly progressive multiple organ
      failure in the first days following the onset of the disease with a high
      probability of death despite ICU therapy. There is poor outcome with both,
      surgical and conservative therapies. Thus, surgery should only be peformed as an
      ultima ratio.

PMID- 17176930
TI  - [Comments on the Report on the Environment and Health in high risk areas of
      Sardinia, Italy].

PMID- 17176931
TI  - [A global strategy for primary prevention of cancer is needed].

PMID- 17176933
TI  - [Clemency and work accidents].

PMID- 17176932
TI  - [Veterans of the Balcan wars and depleted uranium: what the Italian
      epidemiologists would like to know].

PMID- 17176934
TI  - [Manfredonia thirty years later].

PMID- 17176935
TI  - [Mortality and hospital admissions in the industrial area of Civitavecchia, 1997
      2004].
AB  - OBJECTIVE: the industrial area of Civitavecchia (central Italy) has been object
      of concern because of several sources of environmental contamination potentially
      affecting the residential communities: a harbor, a cement factory and several
      power plans are present in the area. A coal power plant is currently under
      construction. The aim of the study is to evaluate the health of residents in the
      area, through the analysis of the mortality registry and the hospital discharge
      records. DESIGN: cause and gender specific indirect Standardized Mortality (1997
      2001) and Hospitalization (1997-2000 and 2001-2004) Ratios were computed, with
      95% Confidence Intervals, using regional population as reference. RESULTS:
      mortality and morbidity excesses for cancer were observed, in particular an
      increased mortality for lung cancer (observed 134, SMR= 120) and for malignant
      neoplasm of pleura (observed 8, SMR= 516) were detected among men. An increased
      frequency of hospital admissions for asthma was observed among children aged 0-14
      (period 1997-2000: males, observed 73, SHR= 177; females, observed 40, SHR= 157).
      Finally an significantly increased incidence of renal diseases was recorded by
      the Lazio Dialysis Registry in the period 2001-2004 (observed 28, SHR= 156).
      CONCLUSION: in view of the environmental changes of the area, the excesses
      observed in this study suggest the need for epidemiologic monitoring found in
      excess (lung and pleural cancer, respiratory diseases among children, renal
      diseases) in the area.

PMID- 17176936
TI  - [Mortality and hospital discharges in the population of Biancavilla (Sicily)
      contaminated by natural fibres].
AB  - OBJECTIVE: The volcanic area of Biancavilla (Sicily Italy) has been included by
      the Italian national law among the areas of "environmental reclamation" due to
      the presence of amphibole fluoro-edenitic fibres in the environment. The aim of
      the study was to evaluate the health of residents in the area, through the
      analysis of the mortality registry and the hospital discharge records. DESIGN:
      Age, cause and gender specific indirect standardized mortality ratios SMR (1995
      2000) and morbidity ratios SHR (2001-2003) were computed with 95% confidence
      intervals, using the population of surrounding municipalities as reference.
      RESULTS: statistically significant increases in mortality and morbidity were
      observed, both in men and women, for malignant pleural neoplasms (mortality: men
      SMR= 700, 6 observed; women SMR= 840, 3 observed; hospital admissions: women SHR=
      1210, 5 observed), cardiovascular diseases (mortality: men SMR= 115, 267
      observed, women SMR= 115, 278 observed; hospital admissions: men SHR= 109, 631
      observed; women SHR= 114, 528 observed) and respiratory diseases (mortality: men
      SMR= 164, 68 observed; women: SMR= 215, 44 observed; hospital admissions: men
      SHR= 139, 558 observed, women SHR= 125, 374 observed). CONCLUSIONS: the excesses
      observed in this study are consistent with previous findings and suggest the need
      for further investigations aimed at improving the knowledge of the mineralogical
      aspects of the fibres, the assessment of human exposure and at estimating the
      prevalence of pleural plaques and lung fibrosis.

PMID- 17176937
TI  - [An increased mortality from lung cancer among workers of a bright electroplating
      factory].
AB  - OBJECTIVE: to evaluate cancer mortality especially from lung tumours, in a cohort
      of workers of a bright electroplating factory, an industrial activity suspected
      of increasing the risk of cancer because of exposure to hexavalent chromium.
      Workers of this and other similar factories have been the target of a health
      surveillance program in the early '80s. DESIGN: the cohort members have been
      selected from the roster of employees as workers or technical clerks with at
      least 6 month of presence between the beginning of the activity (January 1968)
      until December 1994. Vital status has been updated to December 2003. The
      mortality rates of both the Italian and regional population have been used as
      standards. RESULTS: mortality from lung cancer was strongly increased among
      workers (based on 7 deaths among males, and one among females). Among males, lung
      cancer mortality was stratified by duration of work, latency and period of entry:
      the excess is evident in all categories and appeared higher among the workers
      recruited in more recent years. CONCLUSION: we suggest that the results are in
      agreement with the hypothesis of an occupational exposure to a carcinogenic
      hazard, as observed in other studies, and correlates with the increase of
      chromosomal aberrations observed in the past among these workers. This type of
      industrial activity deserves more epidemiological studies and close attention on
      the side of industrial hygiene.

PMID- 17176938
TI  - [Prevalence of dementia in Tuscany: results from four population-based
      epidemiological studies].
AB  - OBJECTIVE: to provide information on epidemiology of dementia in Tuscany needed
      to plan for dedicated health and social services. DESIGN: analysis of pooled
      baseline data from 4 population-based longitudinal studies. SETTING: 4
      municipalities in Tuscany. PARTICIPANTS: 4,056 elderly subjects enrolled in 4
      longitudinal studies. MAIN OUTCOME MEASURES: age- and sex-specific dementia
      prevalence rates and estimated number of demented people, by degree of cognitive
      impairment and BADL disability in the elderly population of Tuscany. RESULTS: out
      of the evaluated subjects, 293 are demented. Prevalence of dementia increases
      from about 1 % in the 65-69 age group to about 28 % in the 90+ age group both
      among women and men. About 43% of the demented study subjects suffer from severe
      mental deterioration (MMSE < 14) and56% are disabled in at least one Basic
      Activity of Daily Living (BADL). We estimate that about 19 thousand demented
      elderly men and 40 thousand demented elderly women are currently living in
      Tuscany of whom 26 thousand severely mentally impaired and 34 thousand disabled
      in at least one BADL. The resulting overall dementia prevalence standardised on
      the Italian 65+ population is 5,3% for men and 7,7% for women. CONCLUSIONS: these
      estimates could be used as a basis for the evaluation and the planning of social
      and health care services dedicated to demented people.

PMID- 17176939
TI  - [PM 10 exposure and asthma exacerbations in pediatric age: a meta-analysis of
      panel and time-series studies].
AB  - OBJECTIVE: review of the time series and panel studies on the short term effects
      of PM10 on the increases of the illness in childhood. DESIGN: meta-analysis of
      panel and time-series studies. METHODS: all studies cited in PubMed that were
      published between 1990 and 2003 were selected. The results of individual studies
      were combined to provide an overall estimate of the effect of PMl0 exposure on
      hospital admissions or emergency room visits for asthma, the frequency of
      asthmatic symptoms (wheezing and cough), the use of anti-asthma medications (in
      addition to regular therapy) and lung functioning (peak expiratory flow PEE
      1/min) using fixed effects models. Random effects models were used (ORRE or
      betaRE, 95% CI) when heterogeneity (p <0.10) was present. The presence of
      publication bias was tested using Egger's test and the bias was corrected with
      the "trim and fill" method RESULTS: ten time series studies and 23 panel studies
      fit the search criteria. Exposure to PM10 was associated with an increase in
      hospitalizations for asthma (ORRE= 1.017, 95% CI 1.008;1.025), with episodes of
      wheezing (ORRE= 1.063, 95% CI 1.038;1.087) and coughing (ORRE= 1.026, 95% CI
      1.013;1.039), in the use of medications for asthma (ORRE= 1.033, 95% CI
      1.008;1.059) and to a decrease in lung function (PRE=-0.269, 95% CI -0.451;-0.
      087). We observed heterogeneity and publication bias. The correction for
      publication bias mitigated the estimates of risk but the most important impact on
      the results was due to a single, multicenter european study (PEACE) that was very
      influential CONCLUSION: exposure to PM10 was associated with an increase in
      hospitalizations for asthma and, in asthmatic children, with the frequency of
      asthmatic symptoms (wheezing and cough), the use of anti-asthma medications (in
      addition to regular therapy) and a decrease in lung functioning. Additional
      research is necessary to explain the causes of the heterogeneity in the
      estimates.

PMID- 17176940
TI  - [Road and home-accident injuries of infants and adolescents in the Lazio region.
      Results of an integrated surveillance system].
AB  - OBJECTIVE: road traffic and home accidents are one of the leading causes of death
      for infants and adolescents between 0-18 years of age. This study aimed to
      describe the injuries of children in the Lazio Region, in the year 2000. DESIGN:
      retrospective cohort study. SETTING: road traffic and home accident injury visits
      to all Emergency Departments (ED) in the Lazio region during 2000, Hospital
      discharges in the region during 2000-2001, integrated through deterministic
      linkage strategy PARTICIPANTS: all children aged 0-18 who visited one of the ED
      for home or road traffic injuries. MAIN OUTCOME MEASURES: we computed ED visits
      and hospitalisation rates and stratified them by sex, age and place of residence.
      Cases were classified by body region and type of lesion. IRR and 95% confidence
      intervals have been estimated using Poisson Regression. RESULTS: the rate of home
      accident visits was particularly high among children aged 1-5 years (55.2/1000),
      while the highest rate for road traffic injuries was in 14-18 year old children
      (53.8/1000). Girls had a lower hospitalisation rate than boys. Higher
      hospitalisation rates were found for children living outside of Rome. The body
      region most frequently injured in road traffic accidents was the lower
      extremities (28.4%), while most frequently injured in home accidents was the head
      and neck (34.8%). CONCLUSION: this study shows how integrating different systems
      of surveillance can provide a more complete picture of injuries from road and
      home accidents, that is difficult to obtain using other sources. The youngest
      children are at high risk of home accidents while teen-agers are at risk for road
      traffic injuries.

PMID- 17176941
TI  - [The HIV epidemiology in province of Modena: use of two different sources of
      data].
AB  - OBJECTIVE: to analyse demographic characteristics and risk factors of people
      living with HIV and to compare data from the surveillance system for new HIV
      diagnoses with those from the National AIDS Registry (RAIDS). DESIGN: comparison
      of two surveillance systems. SETTING: province of Modena. PARTICIPANTS: cases
      reported to the RAIDS and to the HIV surveillance system, from 1985 to 2004
      regarding residents in the province of Modena. MAIN OUTCOMES: number of cases and
      incidence, by exposure categories, age, and gender. RESULTS: from 1985 to 2004,
      615AIDS cases and 1731 new HIV diagnoses were reported among residence in the
      province of Modena. The incidence of AIDS progressively decreased after 1995,
      whereas incidence of new HIV diagnoses remained stable since 1994 with annual
      rates up to three-fold higher than those reported for the AIDS cases. Individuals
      with a new HIV diagnosis were younger (<30 years of age), with a higher
      proportion of females and heterosexuals compared to AIDS cases. The most
      represented age group among AIDS cases was 30-49 years whereas it was <30 years
      for newly diagnosed HIV cases. The proportion of intravenous drug users decreased
      over time both among new AIDS cases and new HIV diagnoses, whereas the proportion
      of cases attributed to sexual transmission increased. The proportion of
      foreigners among newly diagnosed HIV cases was twice as high as among AIDS cases.
      CONCLUSIONS: this study shows that, especially after the introduction of highly
      active antiretroviral therapies, information on AIDS cases has become less
      representative of the trends to HIV epidemic. Therefore, AIDS surveillance
      systems should be combined with local surveillance systems on new HIV diagnoses.

PMID- 17176942
TI  - [End-of-life medical decisions: study of physician's opinions in four Italian
      centres].
AB  - OBJECTIVE: Knowing the physicians' opinions on end-of-life decisions. DESIGN: In
      2002, in the context of an European collaborative study (EURELD) a structured
      questionnaire has been sent to the physicians of the 9 specialties mostly
      involved in the assistance of terminal patients. The questionnaire asked to
      express an opinion on 13 statements on end-of-life decisions and to express
      his/her intention to behave about 4 hypothetical clinical cases. SETTING: four
      Italian centres: Florence-Prato, Venice, Trento and Bologna. PARTICIPANTS: 1508
      questionnaires were studied, the response rate ranged between 34% (Firenze) to
      50% (Trento). RESULTS: In the univariate analysis, there were no significant
      differences between centres for the 13 statements on end-of-life decisions. In
      all centres, about one third physicians accepted euthanasia; about one half
      supported advance directives whereas most physicians would have withheld
      treatment on the request of patient or intensified the alleviation of symptom and
      pain. The intended behaviours of withholding treatment, intensifying the
      alleviation of pain/symptoms, euthanasia, deep sedation until death were more
      frequently expressed in case of the request of patient than on the physicians own
      initiative or on request of the family CONCLUSION: The physicians' attitudes were
      homogeneous between the various centers and they may well be representative of
      the phenomenon which has been investigated, at least in Northern-Central Italy.

PMID- 17176943
TI  - Comparison of alternative modelling techniques in estimating short-term effect of
      air pollution with application to the Italian meta-analysis data (MISA Study).
AB  - In 2002, serious criticism was raised about the use of standard statistical
      software (Splus, SAS, Stata) to fit Generalized Additive Models (GAM) to
      epidemiological time series data. This criticism concerns convergence problems of
      the backfitting algorithm and inappropriate use of a linear approximation in
      estimating standard errors of estimates for parametric terms, such as the effect
      of air pollution. Here we analysed the association between PM10 and
      Mortality/Hospital Admissions in the Italian Meta-analysis of Short-term effects
      of Air pollutants (MISA) using two alternative approaches that are not affected
      by the same drawbacks: GAM with penalized regression spline fitted by the direct
      method in R (GAM-R) software and Generalized Linear Models with natural cubic
      spline (GLM+NS). A sensitivity analysis is also provided varying number of
      degrees of freedom for the seasonality spline and modality of adjustment for
      confounding effect of temperature. Published theoretical results and a simulation
      study are provided in order to explain discrepancies between GLM+NS and GAM-R
      estimates. We conclude that in general the fully parametric GLM+NS approach
      retains better statistical properties than GAM-R that could bring to biased air
      pollution effect estimates unless a certain degree of under-smoothing for
      seasonality spline is settled.

PMID- 17176944
TI  - [The role of asbestos fibre dimensions in the pathogenesis and prevention of
      mesothelioma].
AB  - The particular point of view, recently published by Gerolamo Chiappino, on the
      pathogenetic role of asbestos fibres size in the origin of mesothelioma and on
      the possibility of mesothelioma prevention until the middle of the '80s needs to
      be critically clarified. The suggestion of an exclusive role of ultrashort and
      ultrathin fibres in the origin of mesothelioma is based on a biased
      interpretation of the literature. A review of the epidemiological, experimental,
      and molecular literature suggests that Chiappino's statements on the role of
      dose, dose-response effect, and genetic susceptibility are scientifically unsound
      Chiappino states that, in the past, in the workplaces where use and exposure to
      asbestos were not stopped, any reduction in the intensity of exposure by means of
      dust control measures or personal protective equipment would not have contributed
      to reduce the frequency of mesothelioma. In the authors' opinion the underlying
      assumptions are invalid.

PMID- 17176945
TI  - [Ethics of observational studies: are specific rules useful?].

PMID- 17176946
TI  - [HIA (Health Impact Assessment) of Florence incinerator: local doctors speak up].

PMID- 17176947
TI  - FLOTAC, a novel apparatus for a multivalent faecal egg count technique.
AB  - Faecal egg count (FEC) techniques are widely used for parasitological diagnosis
      in humans and animals. They are also used to measure the prevalence and intensity
      of infections for epidemiological surveys, to quantify the efficacy of
      chemotherapies, and to detect anthelmintic resistance. They assess the number of
      parasitic elements (eggs, larvae, oocysts) present in the faecal samples,
      expressed per gram of faeces, and are based on the microscopic examination of an
      aliquot of faecal suspension from a known volume of a faecal sample. In the
      present paper a novel multivalent FEC technique, the FLOTAC technique, is
      described. It is based on flotation in centrifuge and translation of the apical
      portion of the floating suspension, and gives eggs/larvae/oocyst counts in
      quantities of faeces up to 1 gram. A novel apparatus, the FLOTAC, has been
      developed and patented in order to carry out this technique. It is a cylindrical
      shaped device, made of unbreakable plastic, and holds two sample flotation
      chambers, which are 5 ml each for a total volume of 10 ml, with two ruled grids
      (18 x 18 mm). Each grid contains 12 equidistant ruled lines that are transparent,
      and hence permit the counting of parasitic elements under them. The FLOTAC
      apparatus is also very useful in order to recover parasitic elements after
      flotation.

PMID- 17176948
TI  - [Gastrointestinal parasites in goat farms from Bergamo province (Lombardy, north
      Italy)].
AB  - A survey on gastrointestinal parasites in goat farms in Bergamo province was
      carried out from May 2005 to January 2006. Thirty-one dairy goat farms and 836
      adult female goats were examined. Faecal sampling was carried out before the
      antihelminthic treatments, and the sampling times were grouped in three seasonal
      periods (June-August, September-October and November-March). Faecal exams were
      carried out by a McMaster method and eggs per gram (EPG) were calculated for each
      gastrointestinal parasite. Differences in prevalence of Strongylida, Trichuris
      and Nematodirus were found between farms with goats on pasture and those where
      animals were permanently housed indoor. Strongyloides spp. showed higher values
      of prevalence in goats housed indoor. With regard to the sampling seasons,
      Strongylida eggs were more prevalent in summer while Nematodirus in winter in
      goats at pasture. Strongyloides occurred more frequently in autumn in stabled
      goats.

PMID- 17176949
TI  - [Biomorphology of gastrointestinal nematodes of small ruminants].
AB  - Under the term gastrointestinal nematodes are included numerous parasites species
      of livestock belonging to the families Strongyloididae (Strongyloides),
      Strongylidae (Chabertia, Oesophagostomum) Trichostrongylidae (Trichostrongylus,
      Ostertagia, Teladorsagia, Cooperia, Marshallagia), Molineidae (Nematodirus),
      Ancylostomatidae (Bunostomum) and Trichuridae (Trichuris). This paper reviews the
      biomorphology aspects of these parasites as well as the controversy by the
      taxonomists in the classifications.

PMID- 17176950
TI  - [Biology of gastrointestinal nematodes of ruminants].
AB  - The development and survival of free-living stages of gastro-intestinal nematodes
      of small ruminants are influenced by several abiotic and biotic factors. Within
      the abiotic factors, most important are the environmental temperature and
      humidity. They regulate the development of larvae from eggs dispersed on the
      pasture by the animals faeces. Each parasite species that infect ruminants
      requires a different time to development, depending on temperature and humidity.
      Among trichostrongylids, Ostertagia, Teladorsagia and Nematodirus show a strong
      adaptation to low temperatures. Nematodirus larvae are able to survive to winter
      inside the egg shell. Temperature and humidity influence the distribution and
      survival of larvae on pasture. The larval third stage can migrate from faeces to
      pasture vegetation and they accumulate at the basis of vegetation where stay
      during the day or in the soil to avoid the desiccation. The forage species
      affects the migration of larvae on herbage too. Many biological factors
      contribute to disperse the larvae on the pasture. Dung burying beetles,
      coprophagous beetles and earthworms can greatly reduce the larvae of some
      trichostrongylids on pasture. They contribute to the spread of the faecal
      material on the pasture and allow the larval death as a consequence of drying.

PMID- 17176951
TI  - [Physiopathological mechanisms of abomasal Trichostrongylidae infections in small
      ruminants].
AB  - Abomasal Trichostrongylidae infections are still today an important cause of
      scarce performances in small ruminants, mainly when bred in extensive systems.
      Although morpho-biology, symptomatology, prophylaxis and therapy of these
      infections are well known, other, such as physiopathology, are less investigated.
      The aim of the present note is to review the more important physiopathogenetic
      mechanisms of abomasal Trichostrongylidae infections, with special emphasis to
      Haemonchus spp. and Teladorsagia spp. The parasitic anorexia due to the action of
      gastrin, the defects of digestion due to hypocloridia, the scarce intestinal
      absorption and anaemia caused by H. contortus are discussed. Furthermore, the
      effects of hypersensitivity sometimes caused by these abomasal nematodes are
      examined. A better knowledge of physiopathological mechanisms can represent an
      important factor to understand the relationships between host and parasite,
      useful to set up new diagnostic techniques or new therapeutic and prophylactic
      protocols for sanitary education and control plans of these important and
      widespread parasitic infections.

PMID- 17176952
TI  - [An insight into the epidemiology and economic impact of gastro-intestinal
      nematodes in small ruminants].
AB  - Milk production has been a distinguishing characteristic of sheep breeding since
      antiquity in the Mediterranean area, including Italy, where prehistoric findings
      confirm this particular husbandry activity. In Homer's Odyssey, the description
      of Polifemo's sheep flock organization is remarkably similar to current
      production systems. The ancient roots of this tradition have grown into an
      important economic reality, with excellent levels of milk production and
      apporoximately 65 typical cheeses. It is interesting to note that the Italian
      word "pecora" (sheep) is believed to have originated from the Latin "pecunia"
      (money). Although heavy production losses are due to parasitic infections, only
      250 papers have been published in the last 50 years in Italy on sheep parasites.
      Differences in climate, environmental factors and production tecniques may
      influence infection prevalence, load and pathogenesis. For this reason,
      prevention must be aimed at the particular epidemiological situation and not
      simply adapted from current schemes used abroad. The aim of this paper is to
      illustrate the epidemiology of ovine gastrointestinal nematodes in Italy and to
      evaluate the economic importance of their control.

PMID- 17176953
TI  - [Value of identification of gastrointestinal nematode third-stage larvae
      recovered from faeces and herbage].
AB  - Strategic parasite control programmes of ruminant gastrointestinal nematodes
      requires the knowledge of parasite population dynamics. In natural conditions,
      ruminants, in particular sheep and goats, are infected by different species of
      gastrointestinal nematodes. The life cycle of these parasites is influenced by a
      number of factors which include climatic variations. Therefore, it is important
      to utilise appropriate methods to identify the parasite population both in the
      host and from the pasture. In this paper faecal larval cultures and pasture
      larval counts used for herd health monitoring of nematode infections are
      discussed.

PMID- 17176954
TI  - [Environmental control of gastrointestinal strongylosis in sheep and goats].
AB  - Gastrointestinal strongylosis are the dominant parasitic infections of sheep and
      goats. The successful control of these parasites cannot be done exclusively with
      anthelmintics, but the first step is an integrated program for environmental
      prophylaxis. The correct planning of the prophylaxis program has to be preceded
      by the analysis of the related problems: (1) the parasitological status of farm
      livestock; (2) knowledge of the farm management; (3) hydrogeological, pedological
      and climatic-environmental aspects. The environmental control strategies can be
      resumed as follows: avoiding animals from different farms to share the same
      pasture; avoiding animals of different age classes to graze together; parcel the
      pastures to permit a rational rotation; rotational grazing of pastures according
      to the seasonal development of parasites; stocking rate; young animals grazing
      ahead of the older animal ones; crop management practices (draining, ploughing,
      harrowing, scrub clearing, fertilizing, etc.). These measures make the habitat
      less suitable for the free-living stages of gastrointestinal strongyles, reducing
      the potential of infection of the same pastures.

PMID- 17176955
TI  - [Therapy and anthelmintic resistance].
AB  - Treatment against nematode parasites in sheep and goats is reviewed. The main
      risk factors for parasitic infection in these hosts are briefly outlined. The
      mechanism of action of the most important chemical groups (imidazothiazoles and
      pyrimidines, benzimidazoles/ pro-benzimidazoles and macrocyclic lactones) to
      which the modern anthelmintic drugs belong are illustrated and discussed with
      particular emphasis on possible selection of anthelmintic resistance. The need
      for strategic integrated control based also on the epidemiological patterns of
      parasitism, the composition and the production of the herd (milk, meat, wool) and
      the potency of the drugs are discussed. The importance of diet and potential
      alternative control measures (nematophagus fungi and natural compounds such as
      tannins) are illustrated.

PMID- 17176957
TI  - [Case report of Elaphostrongylus cervi in a goat in north Italy].
AB  - A case of cerebral nematodiasis in a goat from Lombardy (north Italy) is
      described. Clinical signs, histopathological lesions and the finding of a
      nematode in cerebral tissue sections of the affected animal confirmed the
      diagnosis of infection with Elaphostrongylus cervi.

PMID- 17176956
TI  - [Cysticercus tenuicollis infection in a goat farm].
AB  - An outbreak of acute cysticercosis occurred in six female goats 2-4 years old and
      three 50 days old kids from a goat farm in northern Italy. Goats were usually
      recovered in stable with an outdoor paddock. Post-mortem examination showed a
      massive infection of Taenia hydatigena larvae in the liver, lungs and on the
      peritoneum. All recovered Cysticercus tenuicollis were at immature stage.

PMID- 17176958
TI  - Lymphatic vascular endothelial hyaluronan receptor (LYVE)-1- and CCL21-positive
      lymphatic compartments in the diabetic thymus.
AB  - To explore the biological significance of the lymphatics in the autoimmune
      process, the thymus from non-obese diabetic (NOD) mice was evaluated by
      histochemistry and western blot analysis. Thymic lymphatic endothelial cells
      showed suggestive expression patterns of the functional molecules lymphatic
      vascular endothelial hyaluronan receptor (LYVE)-1, CCL21, CD31 and podoplanin.
      With increasing age, the expression of CCL21 was reduced in the medullary
      epithelial cells and lymphatics. Of note, LYVE-1-expressing lymphatics, filled
      with a cluster of thymocytes, increased in number and size and extended from the
      corticomedullary boundary into the medulla as the insulitis progressed. The
      development of lymphatic compartments was occasionally accompanied by a regional
      disappearance between the cortex and medulla. The CD4- and CD8-positive T cells
      frequently penetrated through the slender lymphatic walls. The epithelial
      reticular cell layer lining the perivascular spaces was extensively stained with
      cytokeratin, but the expression of cytokeratin showed an age-dependent decrease.
      These findings indicate that the occurrence of LYVE-1-expressing lymphatic
      compartments and the alteration of CCL21 expression in the lymphatics may be
      involved in defective thymocyte differentiation and migration, and play a
      significant role in insulitic and diabetic processes.

PMID- 17176959
TI  - Anatomical significance of the nerve to the pyramidalis muscle: a morphological
      study.
AB  - Characteristics of the nerve to the pyramidalis muscle (NPy), including its
      origin, course and distribution, were observed (macroscopically) in detail in the
      present study. The spinal segments that give rise to the nerve vary considerably
      and involve Th12-L2. The course and distribution of the nerve also vary widely.
      The NPy is given off from one of the following: (i) the anterior cutaneus branch
      (Rca) of the intercostals nerve; (ii) the ilioinguinal (li) nerve; or (iii) the
      genital branch (Rg) of the genitofemoral nerve. The NPy can be classified into
      nine types according to features of the course and branching pattern of the Rca
      and li. In three of 67 cases, the pyramidalis muscle had two nerves. Double
      innervated pyramidalis muscles received one nerve from a transitional-type Rca
      (Rcat) and a second nerve derived from one of the superficial Rca (Rcas), li or
      Rg. The NPy derived from the deep Rca (Rcap; Type 1), Rcat (Type 2) and
      containing their features as well as the Type 9 (Rcat + li + Rg) reach the muscle
      from behind. Types 3-8 (not containing features of the Rcap and Rcat) enter the
      muscle from its surface. The branch that gives off the NPy is determined by the
      level of segmental origin, with the segmental origin of branches from the Rca
      (Types 1-4), li (Types 5-6) and Rg (Types 7-9) getting lower in that order. The
      level of segmental origin of the NPy derived from different Rca becomes lower in
      the following order: Rcap (Type 1), Rcat (Type 2), Rcas (Type 3), Rcas' (Rcas
      entering the inguinal canal; Type 4). When the origin of the NPy is from a lower
      segment, the origin of the boundary nerve (Rcap/Rcas) is also deviated downward.
      The changes in the NPy are related to the deviation of the entire lumbar plexus.

PMID- 17176960
TI  - Persistent median artery in the hand: a report with a brief review of the
      literature.
AB  - We encountered a persistent median artery in the forearms and hands bilaterally
      in a 78-year-old Japanese male cadaver during dissection practice at Wakayama
      Medical University. The brachial arteries divided into the ulnar and radial
      arteries. The ulnar artery gave off the median and posterior interosseous
      arteries at the same point, although the anterior interosseous artery was not
      found. The median artery ran along the median nerve and bifurcated in the hand.
      In the superficial layer of the palm, one branch of the median artery ran to the
      ulnar side of the thumb, whereas the other passed to the second interdigital
      space. The ulnar artery reached the third and fourth interdigital spaces and the
      ulnar side of the little finger, and showed no anastomosis with the median artery
      in the superficial layer of the palm. The radial artery did not give off the
      superficial palmar branch. Therefore, the formation of the superficial palmar
      arch was incomplete. In the deep layer of the palm, the radial artery formed the
      deep palmar arch with the deep palmar branch of the ulnar artery and gave off the
      princeps pollicis artery. In the dorsum of hand, the radial artery passed over
      the first dorsal interosseous muscle to the index finger and communicated with
      the palmar pollical artery from the median artery in the first interosseous
      space. The present study reports an unusual variation of the persistent median
      artery in the hand and briefly reviews the literature about the median artery.

PMID- 17176961
TI  - Number, distribution and size of retinal ganglion cells in the jungle crow
      (Corvus macrorhynchos).
AB  - A retinal ganglion cell density map was generated using Nissl-stained retinal
      whole mounts from the jungle crow (Corvus macrorhynchos). The total number,
      distribution and size of these cells were determined in the area centralis, as
      well as in temporal, nasal, dorsal and ventral retinal regions. The mean total
      number of ganglion cells was estimated to be 3.6 x 10(6). The highest densities
      were found in the area centralis (25 600 /mm2) and the dorso-temporal part of the
      retina, suggesting the highest quality of vision. This density diminished nearly
      concentrically from the central area towards the retinal periphery. The number of
      ganglion cells was highest in the temporal retina followed, in order, by the
      nasal, dorsal and ventral retinal regions. Based on ganglion cell size, the
      retina seemed to consist of the following five regions: central, temporal, nasal,
      dorsal and ventral. Ganglion cell size ranged from 16 to 288 microm2, with
      smaller cells predominating in central regions above the optic disc and larger
      cells comprising more of the peripheral regions. The present study showed two
      highly populated areas of ganglion cells in the crow retina and it is expected
      that the crow retina provides well-developed monocular and binocular vision.

PMID- 17176962
TI  - Investing in the future of health.

PMID- 17176963
TI  - Dialogue. Nonprofit health care organizations and the public trust.

PMID- 17176964
TI  - The impact of elder care on women's labor supply.
AB  - Adult daughters traditionally have served as primary caregivers for frail
      unmarried adults, but the levels of care they have provided in the past may
      interfere with their growing work responsibilities. This paper examines the
      impact of time transfers to elderly parents on labor supply at midlife. Using a
      sample of women ages 55 to 67 in the Health and Retirement Study, we estimate
      panel data models of annual hours of paid work controlling for the endogeneity of
      time assistance to parents. The results indicate that time help to parents
      strongly reduces female labor supply at midlife.

PMID- 17176965
TI  - Aging without Medicare? Evidence from New York City.
AB  - Medicare and Social Security often are assumed to provide universal coverage for
      the population age 65 and older. Evidence from New York City raises doubts. Data
      from the Statewide Planning and Research Cooperative System, the Centers for
      Medicare and Medicaid Services, the Social Security Administration, and the U.S.
      Bureau of the Census provide evidence that 16% to 20% of New York City residents
      age 65 and older lack such coverage. Noncoverage is not unique to this city, but
      it may be particularly common there. Noncoverage is pronounced in, but not
      limited to, certain immigrant groups. Because the population share covered by
      Medicare increases with age and most hospitalizations not covered by Medicare are
      paid by Medicaid, Medicaid gradually may be replacing Medicare as the payer for
      hospitalizations for a substantial share of the 65+ population in New York City.

PMID- 17176966
TI  - Health insurance and access to care among Social Security Disability Insurance
      beneficiaries during the Medicare waiting period.
AB  - For most Social Security Disability Insurance (SSDI) beneficiaries, Medicare
      entitlement begins 24 months after the date of SSDI entitlement. Many may
      experience poor access to health care during the 24-month waiting period because
      of a lack of insurance. National Health Interview Survey data for the period 1994
      1996 were linked to Social Security and Medicare administrative records to
      examine health insurance status and access to care during the Medicare waiting
      period. Twenty-six percent of SSDI beneficiaries reported having no health
      insurance, with the uninsured reporting many more problems with access to care
      than insured individuals. Access to health insurance is especially important for
      people during the waiting period because of their low incomes, poor health, and
      weak ties to the workforce.

PMID- 17176968
TI  - Tort law and medical malpractice insurance premiums.
AB  - This paper estimated the effects of tort law and insurer investment returns on
      physician malpractice insurance premiums. Data were collected on tort law from
      1991 through 2004, and multivariate regression models, including fixed effects
      for state and year, were used to estimate the effect of changes in tort law on
      medical malpractice premiums. The premium consequences of national policy changes
      were simulated. The analysis found that the introduction of a new damage cap
      lowered malpractice premiums for internal medicine, general surgery, and
      obstetrics/gynecology by 17.3%, 20.7%, and 25.5%, respectively. Lowering damage
      caps by dollar 100,000 reduced premiums by 4%. Statutes of repose also resulted
      in lower premiums. No other tort law changes had the effect of lowering premiums.
      Simulation results indicate that a national cap of dollar 250,000 on awards for
      noneconomic damages in all states would imply premium savings of dollar 16.9
      billion. Extending a dollar 250,000 cap to all states that do not currently have
      them would save dollar 1.4 billion annually, or about 8% of the total. A negative
      effect on malpractice premiums was found for the Dow Jones industrial average,
      but not for bond prices; effects of the Nasdaq index were not significant for
      internal medicine, but were marginally significant for surgery and obstetrics
      premiums.

PMID- 17176967
TI  - Health insurance coverage for vulnerable populations: contrasting Asian Americans
      and Latinos in the United States.
AB  - This paper examines the role that population vulnerabilities play in insurance
      coverage for a representative sample of Latinos and Asians in the United States.
      Using data from the National Latino and Asian American Study (NLAAS), these
      analyses compare coverage differences among and within ethnic subgroups, across
      states and regions, among types of occupations, and among those with or without
      English language proficiency. Extensive differences exist in coverage between
      Latinos and Asians, with Latinos more likely to be uninsured. Potential
      explanations include the type of occupations available to Latinos and Asians,
      reforms in immigration laws, length of time in the United States, and regional
      differences in safety-net coverage. Policy implications are discussed.

PMID- 17176969
TI  - Economic profiling of physician specialists: use of outlier treatment and episode
      attribution rules.
AB  - This paper examines the influence of episode attribution methodology and cost
      outlier methodology on the accuracy of physicians' economic profiles. Four years
      of claims data from a mixed model HMO were processed using the leading episode
      grouper software. Episode grouped results then were applied to construct input
      distributions for a simulation model. For each of four specialties (cardiology,
      family practice, general surgery, and neurology), we employed sets of 18
      simulations to investigate the effects of three alternative episode attribution
      methodologies and six alternative cost outlier methodologies on sensitivity,
      specificity, and positive predictive error in classifying cost-efficient and cost
      inefficient physicians. For identification of cost-efficient physicians, the most
      accurate profiling results were obtained when Winsorizing outliers at 2% and 98%
      of episode-type cost distributions, and attributing responsibility for episode
      costs to physicians who accounted for at least 30% of associated professional and
      prescribing fees. No consistent combination of outlier methodology and episode
      attribution rule was found to be superior for identifying cost-inefficient
      physicians.

PMID- 17176970
TI  - Unstable inferences? An examination of complex survey sample design adjustments
      using the Current Population Survey for health services research.
AB  - Statistical analysis of the Current Population Survey's Annual Social and
      Economic Supplement is used widely in health services research. However, the
      statistical evidence cited from the Current Population Survey (CPS) is not always
      consistent because researchers use a variety of methods to produce standard
      errors that are fundamental to significance tests. This analysis examines the
      2002 Annual Social and Economic Supplement's (ASEC) estimates of national and
      state average income, national and state poverty rates, and national and state
      health insurance coverage rates. Findings show that the standard error estimates
      derived from the public use CPS data perform poorly compared with the survey
      design-based estimates derived from restricted internal data, and that the
      generalized variance parameters currently used by the U.S. Census Bureau in its
      ASEC reports and funding formula inputs perform erratically. Because the majority
      of published research (both by academics and Census Bureau analysts) does not
      make use of the survey design-based information available only on the internal
      ASEC data file, we argue that the Census Bureau ought to use alternative methods
      for its official ASEC reports. We also argue that for public use data the Census
      Bureau should produce a set of replicate weights for the ASEC or release a set of
      sample design variables that incorporate statistical "noise" to maintain
      respondent confidentiality (e.g., pseudo-primary sampling units) as other federal
      government surveys do. This is essential to make appropriate inferences using the
      ASEC data regarding statistical significance and estimate variance for health
      policy analysis.

PMID- 17176971
TI  - Health care needs of aging adults: unprecedented opportunities for social work.

PMID- 17176973
TI  - Worries of the oldest-old.
AB  - With the emerging population of the oldest-old (those ages 85 and older), it is
      crucial to understand and prepare for their psychosocial needs. Worry is linked
      to psychological well-being and physical health, but little is known about the
      oldest-old's everyday worries. The authors explored four research questions: (1)
      What are the worries of the oldest-old? (2) What are their specific dimensions of
      worry? (3) How alike or different are the worry patterns over time? (4) What
      factors are related to variations in the pattern of change in worry? A
      convenience sample of 193 community-dwelling people ages 85 and older was
      recruited to examine various aspects of health and well-being between 1986 and
      1995. This article reports on the survivors (N = 23) across three time points,
      waves 1, 4, and 5. The findings suggest that the very old mainly worry about
      health and memory and that, although worry increased over the study period, there
      were variations in the pattern of worry over time. Results of t tests show that
      at wave 4 elderly respondents with a higher level of worry reported more frequent
      social contact than those with a lower level of worry. Implications for social
      work practice and future research are discussed.

PMID- 17176972
TI  - Functional limitations and religious service attendance among African American
      and white older adults.
AB  - Church attendance is associated with improved health and well-being among older
      adults, but older adults with functional limitations may have difficulty
      attending church services. This article examines differences in the association
      between functional limitations and church attendance in a sample of 987 elderly
      African American and white individuals. African American and white elderly people
      without limitations attended church at virtually the same rate (69 percent).
      Despite their higher scores on religiousness measures, elderly African Americans
      with one or more limitations were significantly less likely to attend church
      regularly than were white counterparts. Health status measures did not help
      explain older African Americans' lower attendance rates. Differences in
      attendance were associated primarily with educational attainment and cognitive
      functioning. The article recommends social work intervention to reduce barriers
      to church attendance for older adults who want to attend services.

PMID- 17176974
TI  - Organizational characteristics influencing nursing home social service directors'
      qualifications: a national study.
AB  - This research sought to identify organizational characteristics associated with
      the amount of professional qualifications among a nationally representative
      sample of nursing home social service directors. A self-administered survey was
      sent to directors in 675 facilities randomly sampled from a federal database,
      excluding facilities with fewer than 120 beds that are not required to staff a
      full-time social worker. The response rate was 45 percent (N = 299). Univariate
      results showed that most respondents possessed a social work degree, most lacked
      licensure, and few were clinically supervised. A multiple regression analysis
      found that nonprofit, independently owned facilities in rural areas staffed
      social service directors who were significantly more qualified than directors in
      for-profit, chain-affiliated facilities in urban and suburban areas. Facilities
      with fewer psychosocial deficiencies and higher occupancy rates employed social
      service directors with greater qualifications. The implications of these findings
      for social work education, practice, policy, and research are discussed.

PMID- 17176975
TI  - Race disparities in health among older adults: examining the role of productive
      engagement.
AB  - Productive engagement is a potential pathway to health for older adults, but this
      relationship varies by race. This study examines the relationship of productive
      engagement to the health and observed health disparities of older African
      American and white adults. Productive activities include formal and irregular
      paid employment, caregiving, volunteering, and informal social assistance. The
      authors analyzed longitudinal panel data on individuals ages 60 and older from
      the Americans' Changing Lives survey with generalized estimating equations
      methods. Indicators of self-rated health and functional status were regressed
      separately on measures of productive engagement after accounting for
      sociodemographic differences and prior levels of health. Analyses were stratified
      by race and compared. Engagement in productive activities predicts better
      functional status for both groups, but higher self-rated health only among white
      adults. Number of activities performed was positively related to both health
      measures for all individuals, and hours of engagement and the ratio of paid to
      unpaid hours did not predict health outcomes.

PMID- 17176976
TI  - Stress constellations and coping styles of older adults with age-related visual
      impairment.
AB  - Narrative data from two earlier studies of adaptation to age-related visual
      impairment were examined for constellations of stressors and coping styles. In
      the course of previous qualitative analyses, the researchers identified stress
      and coping codes according to behavioral, psychological, and social domains using
      a grounded theory approach. In the present study, these qualitative data were
      extracted into a quantitative format and subjected to cluster analysis to better
      understand stress constellations and coping styles in this population. The
      analysis yielded five constellation groups: stoics, complainers, taciturns,
      sentimentalists, and articulates. Cluster analysis of self-reported coping styles
      yielded five groups that included mavericks, autonomous, pragmatists, hermits,
      and nonchalants. Across groups, there was a pattern of limited efforts to obtain
      vision rehabilitation services for instrumental needs, along with low acceptance
      of vision loss and the desire to strengthen personal resources. Implications for
      practice and research are discussed.

PMID- 17176977
TI  - An examination of the social networks and social isolation in older and younger
      adults living with HIV/AIDS.
AB  - This study examined social networks and social isolation in older (50 years or
      more) and younger (ages 20 to 39) adults with HIV/AIDS. The author conducted
      interviews with 88 individuals living with HIV/AIDS in the Pacific Northwest.
      Both groups' social networks had similar patterns; however, older adults were
      more likely to live alone. More than 38 percent of older adults and 54 percent of
      older adults of color were at risk of social isolation compared with 25 percent
      of those 20 to 39 years of age. Older men and older adults of color had
      significantly lower scores on the social network scale than others. Having a
      confidant and receiving instrumental support were significantly correlated with
      reduced HIV stigma. Implications for social work practitioners are discussed.

PMID- 17176978
TI  - The trouble with health savings accounts: a social work perspective.

PMID- 17176979
TI  - Investigating the existence of quantum metabolic values in non-Hodgkin's lymphoma
      by 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography.
AB  - OBJECTIVES: To investigate the existence of quantum metabolic values in various
      subtypes of non-Hodgkin's lymphoma (NHL). METHODS: Fifty-eight patients with
      newly diagnosed NHL and positron emission tomography (PET) performed within three
      months of biopsy were included. The standardized uptake value (SUV) from PET over
      the area of biopsy and serum glucose [Glc] were recorded. The group glucose
      sensitivity(G) for indolent and aggressive NHL was obtained by linear regression
      with ln(SUV) = G x ln[Glc] + C, where C is a constant for the group. Finally, the
      individual's glucose sensitivity (g) was obtained by g = {ln(SUV)-C}/ln[Glc],
      along with their means in various subtypes of NHL. To further investigate the
      influence of extreme [Glc] conditions, the SUVs corrected by the individually
      calculated g at various glucose levels, [Glc'] using SUV' =SUV x
      {[Glc']/[Glc]}(g), were compared to the original SUVs for both indolent and
      aggressive NHL. RESULTS: The averaged g (=G) for aggressive was significant
      different from that for indolent NHL (-0.94 +/- 0.51 vs. +0.13 +/- 0.10,
      respectively, p < 0.00005). There were significant differences in SUV for [Glc] <
      80 or >110 mg/dl for both types of NHL. Unlike overlap among SUVs between NHL
      subtypes, the g value clearly categorized them into two distinct groups with
      positive (near-zero) and negative g values (around -1) for the indolent and
      aggressive NHLs, respectively. CONCLUSIONS: Distinct quantum metabolic values of 
      1 and 0 were noted in NHL. Aggressive NHL has a more negative value (or higher
      glucose sensitivity) than that of indolent and, thus, is more susceptible to
      extreme glucose variation.

PMID- 17176981
TI  - 2-Deoxy-2-[F-18]fluoro-D-glucose positron emission tomography illustrates two
      visceral tumors in a post kidney transplant patient with multiple cutaneous
      malignancies.
AB  - The success of renal transplantation brings with it the dilemma of managing
      patients with complications from lifelong immunosuppressive therapy.
      Immunosuppressed transplant recipients are a special population with
      significantly increased risk for development of skin cancers. Because malignant
      tumors are increasing as demonstrated on 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)
      positron emission tomography (PET) image, we report the unusual coincidence of
      multiple cutaneous cancers and two visceral malignancies 20 years after renal
      transplantation. The malignancies include basal cell and squamous cell carcinomas
      and malignant fibrous histiocytoma. FDG-PET images show, in this case, visceral
      masses with increased metabolism: one in the left upper lung and one in the
      abdomen, corresponding to individual mass lesions observed on computed tomography
      (CT) images of the chest and abdomen. A fine-needle biopsy of the nodule of the
      left upper lung lobe yielded a diagnosis of a sarcoma. The mass lesion of the
      abdomen had caused bowel obstruction, requiring exploratory laparotomy;
      histopathological findings from the resected mass from the abdomen confirmed the
      diagnosis malignant fibrous histiocytoma. This long-term immune suppressed
      transplant recipient developed viscerally located malignant lesions demonstrated
      by FDG-PET imaging and three types of cutaneous malignancies (skin cancers).

PMID- 17176982
TI  - Resection of isolated pelvic recurrences after colorectal surgery: long-term
      results and predictors of improved clinical outcome.
AB  - BACKGROUND: Recurrence in the pelvis after resection of a rectal or rectosigmoid
      cancer presents a dilemma. Resection offers the only reasonable probability for
      cure, but at the cost of marked perioperative morbidity and potential mortality.
      Clinical decision making remains difficult. METHODS: Patients who underwent
      resection with curative intent for isolated pelvic recurrences after curative
      colorectal surgery from 1988 through 2003 were reviewed retrospectively. Clinical
      and pathological factors, salvage operations, and complications were recorded.
      The primary measured outcome was overall survival. Univariate and multivariate
      analyses were conducted to identify prognostic factors of improved outcome.
      RESULTS: Ninety patients underwent an attempt at curative resection of a pelvic
      recurrence; median follow-up was 31 months. Complications occurred in 53% of
      patients. Operative mortality occurred in 4 (4.4%) of 90 patients. Median overall
      survival was 38 months, and estimated 5-year survival was 40%. A total of 51 of
      86 patients had known recurrences (15 local, 16 distant, 20 both). Multivariate
      analysis revealed that preoperative carcinoembryonic antigen level and final
      margin status were statistically significant predictors of outcome. CONCLUSIONS:
      The resection of pelvic recurrences after colorectal surgery for cancer can be
      performed with low mortality and good long-term outcome; however, morbidity from
      such procedures is high. Low preoperative carcinoembryonic antigen and negative
      margin of resection predict improved survival.

PMID- 17176980
TI  - "Magnetic resonance imaging negative positron emission tomography positive"
      temporal lobe epilepsy: FDG-PET pattern differs from mesial temporal lobe
      epilepsy.
AB  - PURPOSE: Some patients with temporal lobe epilepsy (TLE) lack evidence of
      hippocampal sclerosis (HS) on MRI (HS-ve). We hypothesized that this group would
      have a different pattern of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron
      emission tomography (PET) hypometabolism than typical mesial TLE/HS patients with
      evidence of hippocampal atrophy on magnetic resonance imaging (MRI) (HS+ve), with
      a lateral temporal neocortical rather than mesial focus. PROCEDURES: Thirty
      consecutive HS-ve patients and 30 age- and sex-matched HS+ve patients with well
      lateralized EEG were identified. FDG-PET was performed on 28 HS-ve patients and
      24 HS+ve patients. Both groups were compared using statistical parametric mapping
      (SPM), directly and with FDG-PET from 20 healthy controls. RESULTS: Both groups
      showed lateralized temporal hypometabolism compared to controls. In HS+ve, this
      was antero-infero-mesial (T = 17.13); in HS-ve the main clustering was
      inferolateral (T = 17.63). When directly compared, HS+ve had greater
      hypometabolism inmesial temporal/hippocampal regions (T = 4.86); HS-ve had
      greater inferolateral temporal hypometabolism (T = 4.18). CONCLUSIONS: These data
      support the hypothesis that focal hypometabolism involves primarily lateal
      neocortical rather than mesial temporal structures in 'MRI-negative PET-positive
      TLE.'

PMID- 17176984
TI  - When a cure isn't possible... Do all roads lead to palliation?

PMID- 17176983
TI  - Distal bile duct carcinoma: prognostic factors after curative surgery. A series
      of 112 cases.
AB  - BACKGROUND: The identification of independent prognostic indicators in distal
      bile duct carcinomas (DBDCs) has been limited by the small number of tumors and a
      lack of molecular prognostic markers. Markers assessed in combination may perform
      better than those considered individually. We conducted this study to identify
      prognostic predictors of patients with DBDC with special focus on combination of
      expression of p53 protein and clinicopathological predictors. METHODS: Between
      December 1996 and 2002, 112 consecutive patients undergoing
      pancreaticoduodenectomy in the Eastern Hepatobiliary Surgery Hospital for distal
      bile duct carcinomas were identified in a prospectively collected database. The
      survival of patients was comparable with respect to patient characteristics,
      clinicopathological factors and degree of p53 protein expression followed by a
      univariate and multivariate analysis. RESULTS: Actual 1, 3, and 5-year survival
      rates were 85.7, 50.9, and 25.0%, respectively. By Cox proportional hazards
      survival analysis, the most powerful predictors of survival rate were p53
      expression [relative risk (RR) 5.2, 95% CI 4.8-5.6], pancreatic invasion (RR 5.6,
      95% CI 4.3-6.9), lymph nodes metastasis (RR 3.9, 95% CI 3.3-4.5), and operative
      time (RR 1.8, 95% CI 1.5-2.1). CONCLUSIONS: Overexpression of p53 in DBDC is
      strongly associated with significantly reduced survival, independently of
      clinicopathological prognostic factors. The resection margin status provides
      little independent prognostic information. Longer operative time may have
      unfavorable effect on prognosis of patients with DBDC.

PMID- 17176985
TI  - Tumor location of the lower-inner quadrant is associated with an impaired
      survival for women with early-stage breast cancer.
AB  - BACKGROUND: There is growing evidence that tumors of the inner quadrants
      (especially the lower-inner quadrant) metastasize more often to the internal
      mammary chain (IMC). As these metastases are not investigated, patients with
      lower-inner quadrant tumors have an increased risk of being under-staged and
      under-treated and may therefore have a higher risk of death from breast cancer.
      METHODS: We identified all 1522 women operated for stage I breast cancer between
      1984 and 2002 recorded at the population-based Geneva Cancer Registry. We
      compared breast cancer mortality risk by tumor location with multivariate Cox
      regression analysis that accounted for all factors linked to tumor location and
      survival. RESULTS: Ten-year disease-specific survival was 93% (95%CI: 91-94%).
      Patients with breast cancer of the lower-inner quadrant (n = 118; 7.8%) had an
      importantly increased risk of dying of breast cancer compared to women with
      breast cancer of the upper-outer quadrant (multiadjusted Hazard Ratio: 2.3,
      95%CI: 1.1-4.5, P = 0.0206). The over-mortality associated with this quadrant was
      particularly evident for tumors >10 mm (multiadjusted HR: 3.6, 95%CI: 1.6-7.9, P
      = 0.0016). There was no increased breast cancer mortality risk for tumors located
      in other quadrants. CONCLUSIONS: Tumor location in the lower-inner quadrant is an
      independent and important prognostic factor of stage I breast cancer. Further
      research is needed to evaluate if the over-mortality of patients with stage I
      cancer of the lower-inner quadrant is indeed a result of under-treatment due to
      undetected IMC metastases. If so, patients with stage I breast cancer of the
      lower-inner quadrant are good candidates for systematic IMC investigation.

PMID- 17176986
TI  - Evaluation of three scoring systems predicting non sentinel node metastasis in
      breast cancer patients with a positive sentinel node biopsy.
AB  - BACKGROUND: Completion axillary lymph node dissection (cALND), performed after a
      positive sentinel lymph node biopsy (SLNB) in breast cancer patients, often
      results in no additional positive nodes. Scoring systems have been published to
      aid in the prediction of nonsentinel node metastasis. Our purpose was to assess
      the validity of these scoring systems in our patient population. METHODS: For 39
      consecutive patients who underwent cALND after a positive SLNB, scores were
      calculated using retrospective patient data for each of the three scoring systems
      used. Receiver operating characteristics (ROC) curves were drawn, and the areas
      under the curves were calculated to assess the discriminative power of each
      system. Univariate analysis was performed to assess the predictability of
      individual patient and tumor characteristics. RESULTS: Nonsentinel nodes were
      positive in 23 (59%) patients. The areas under the ROC curves were 0.63, 0.70,
      and 0.68, respectively. The proportion of sentinel nodes that were positive and
      the total number of sentinel nodes retrieved were the only individual predictors
      of nonsentinel node metastasis. CONCLUSIONS: Given the high incidence of
      retrieving no additional metastasis on cALND, individualized patient management
      according to risk is desirable. Scoring systems provide additional information
      regarding the likelihood of metastasis in nonsentinel nodes, but their
      predictability remains less than optimal. The use of scoring systems must be
      applied with caution until future studies provide a more accurate assessment of
      risk for patients with a positive SLNB.

PMID- 17176987
TI  - Degradation dynamics and persistence of imidacloprid in a rice ecosystem under
      West Bengal climatic conditions.

PMID- 17176988
TI  - Effect of drying on organophosphorus pesticide residues in peppermint (Mentha
      piperita L.).

PMID- 17176989
TI  - Lead in soils in paint contaminated residential sites at San Antonio, Texas, and
      Baltimore, Maryland.

PMID- 17176990
TI  - Particulate matter and associated metal levels in a conservation area in the
      remaining tropical forest of Mata Atlantica, Brazil.

PMID- 17176991
TI  - Chromium levels in vegetables and grains grown on tannery effluent irrigated area
      of Jajmau, Kanpur, India: influence on dietary intake.

PMID- 17176992
TI  - Lead, mercury, and nickel in grapevine, Vitis vinifera L., in polluted and
      nonpolluted regions.

PMID- 17176993
TI  - Metal distribution in Pakistani and foreign brands of cigarette tobacco.

PMID- 17176994
TI  - Metal distribution in Pakistani and foreign brands of cigarette ash.

PMID- 17176995
TI  - Characterization of soil and sediment samples collected from the Zadar area,
      Croatia, by GC-ECD PCB analysis and bioassay.

PMID- 17176996
TI  - Soil nitrification and denitrification potentials in a wheat field soil as
      affected by elevated atmospheric CO2 and rice straw incorporation.

PMID- 17176997
TI  - Absence of DNA damage in multiple organs after oral exposure to fluoride in
      Wistar rats.

PMID- 17176998
TI  - Serum heat shock protein (HSP70) and its antibody (Anti-HSP70) levels in male
      foundry workers in Taiwan.

PMID- 17176999
TI  - Assessment of human exposure to aluminum through cooked food monitoring.

PMID- 17177000
TI  - Exposure to airborne asbestos during abatement of ceiling material, window
      caulking, floor tile, and roofing material.

PMID- 17177001
TI  - Asbestos abatement in a location previously improperly abated.

PMID- 17177002
TI  - Continuing organochlorine insecticide mortality in wild birds in New York, 2000
      2004.

PMID- 17177003
TI  - Toxicity of trace metals to juvenile abalone, Haliotis rubra following short-term
      exposure.

PMID- 17177004
TI  - Acute toxicity of hexavalent chromium to European freshwater fish.

PMID- 17177005
TI  - Roundup Biactive modifies cadmium toxicity to Daphnia carinata.

PMID- 17177006
TI  - Comparative toxicities of organotin compounds on fertilization and development of
      sea urchin (Anthocidaris crassispina).

PMID- 17177007
TI  - Response of chamomile plants (Matricaria recutita L.) to cadmium treatment.

PMID- 17177008
TI  - Response of Chlorococcum sp. AZHB to copper and cadmius stress.

PMID- 17177009
TI  - Effects of sodium selenite on methylmercury-induced cell death and on mercury
      accumulation in rat cerebellar neurons in primary culture.

PMID- 17177010
TI  - Naturalistic-observational studies in the framework of ADHD health care.

PMID- 17177011
TI  - Influence of gender on attention-deficit/hyperactivity disorder in Europe--ADORE.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) in girls in Europe is
      poorly understood; it is not known whether they exhibit similar symptom patterns
      or co-existing problems and receive the same type of treatment as boys.
      OBJECTIVE: To examine gender differences for referral patterns, social
      demographic factors, ADHD core symptomatology, co-existing health problems,
      psychosocial functioning and treatment. METHODS: Baseline data from the ADHD
      Observational Research in Europe (ADORE) study, a 24-month, naturalistic,
      longitudinal observational study in 10 European countries of children (aged 6-18
      years) with hyperactive/inattentive/impulsive symptoms but no previous diagnosis
      of ADHD, were analysed by gender. RESULTS: Data from 1,478 children were
      analysed: 231 girls (15.7%) and 1,222 boys (84.3%) (gender data missing for 25
      patients). Gender ratios (girl:boy) varied by country, ranging from 1:3 to 1:16.
      Comparisons showed few gender effects in core ADHD symptomatology and clinical
      correlates of ADHD. Compared with boys, girls had significantly more parent-rated
      emotional symptoms and prosocial behaviour and were more likely to be the victim
      of bullying and less likely to be the bully. Girls and boys had similar levels of
      co-existing psychiatric and physical health problems, and received the same type
      of treatment. CONCLUSIONS: Fewer girls than boys are referred for ADHD treatment,
      but they have a similar pattern of impairment and receive similar treatment.

PMID- 17177012
TI  - Co-existing psychiatric problems in ADHD in the ADORE cohort.
AB  - OBJECTIVE: To study the impact of co-existing psychiatric problems with ADHD on
      behavioural features, psychosocial functioning and quality of life in subjects of
      the ADORE cohort (N=1,478). METHODS: The following six groups of associated
      psychiatric problems with ADHD were compared: oppositional-defiant disorder or
      conduct disorder only (ODD/CD); anxiety or depressive disorder only (ANX/DEP);
      tic/Tourette's disorder only (TIC/Tourette's); developmental co-ordination
      disorder only (DCD); two or more associated conditions; and none. Dependent
      variables included the ADHD Rating Scale-IV, the Strengths and Difficulties
      Questionnaire, the Clinical Global Impression-Severity scale, the Children's
      Global Assessment Scale and the Child Health Illness Profile-Child Edition.
      RESULTS: Having multiple co-existing psychiatric problems increased the severity
      of ADHD in all domains, be it behavioural features, psychosocial impairment or
      deterioration of quality of life. A similar though less consistent pattern
      applied to subjects with co-existing ODD/CD. CONCLUSIONS: The ADORE study
      provides impressive evidence for the far-reaching consequences of co-existing
      psychiatric problems in children with ADHD that warrant intensive consideration
      in clinical assessment and treatment.

PMID- 17177013
TI  - Which factors impact on clinician-rated impairment in children with ADHD?
AB  - OBJECTIVES: To describe the associations between a range of demographic, family
      and clinical factors and clinician-rated measures of global impairment in
      children with ADHD symptoms obtained at the baseline assessment in the ADHD
      Observational Research in Europe (ADORE) study. METHODS: Global impairment was
      measured by clinicians using the Clinical Global Impression-Severity (CGI-S)
      scale and the Children's Global Assessment Scale (CGAS). Associations with
      independent variables were investigated using forward-stepwise regression models.
      RESULTS: For the CGI-S and CGAS analyses, complete data sets were available for
      1,265 and 985 children, respectively. The baseline mean CGI-S score in this
      population was 4.4 (SD 0.9) and the mean CGAS score was 55.0 (SD 10.6). Factors
      significantly associated with increased impairment on both outcome measures were:
      increased severity of ADHD symptoms, increased peer relationship problems and
      presence of oppositional defiant disorder and/or conduct disorder. Also, the
      presence of anxiety and/or depression and the presence of somatic symptoms were
      associated with increased impairment on CGI-S,while family health problems and
      premature birth were associated with increased impairment on CGAS. CONCLUSIONS:
      The severity of clinician-rated impairment in the ADORE sample is increased by
      the presence of disruptive behaviour problems and emotional problems, somatic
      symptoms, peer relationship difficulties, family health problems and premature
      birth.

PMID- 17177014
TI  - Factors related to health-related quality of life (HRQoL) among children with
      ADHD in Europe at entry into treatment.
AB  - OBJECTIVE: To describe the associations between a range of baseline factors
      (demographic, family and clinical) and parent-reported health-related quality of
      life (HRQoL) of children with ADHD taking part in the ADORE study. METHODS: HRQoL
      was rated using the Parent Report Form of the Child Health and Illness Profile
      Child Edition (CHIP-CE). Forward-stepwise linear regression models were used to
      investigate associations with 26 independent variables. Separate models were
      fitted for each of the five CHIP-CE domains (Satisfaction, Comfort, Resilience,
      Risk Avoidance and Achievement) and two subdomains of Achievement (Academic
      Performance and Peer Relations). RESULTS: CHIP-CE domain mean scores were lower
      than community norms, especially for Risk Avoidance and Achievement, indicating a
      low level of HRQoL. Clinical factors significantly associated with a poorer HRQoL
      included ADHD symptoms (inattention, hyperactivity-impulsivity), conduct
      problems, peer relationship problems, having asthma, multiple other somatic
      symptoms and co-ordination problems. Family factors, such as having a parent with
      a health or mental health problem possibly caused by the child's illness, child
      not living with both parents and maternal smoking during pregnancy were also
      associated with a worse HRQoL in some CHIP-CE domains/subdomains. CONCLUSIONS:
      Numerous factors independently impact on the HRQoL of children with ADHD.

PMID- 17177015
TI  - Study design, baseline patient characteristics and intervention in a cross
      cultural framework: results from the ADORE study.
AB  - OBJECTIVE: To describe the methodology and to present the baseline findings of
      the Attention-deficit/hyperactivity Disorder Observational Research in Europe
      (ADORE) study, the primary objective of which is to describe the relationship
      between treatment regimen prescribed and quality of life of children with ADHD in
      actual practice. METHODS: In this 2-year prospective observational study, data on
      diagnosis, prescribed treatment and outcomes of ADHD were collected at seven time
      points by paediatricians and child psychiatrists on 1,573 children recruited in
      10 European countries. The data presented here from the 1,478 patients included
      in the analyses describe the baseline condition, initial treatment regimen
      prescribed and quality of life of families with children with ADHD. RESULTS:
      Patients had a mean age of 9.0 years (SD 2.5) and 84% were male. Physicians
      diagnoses were made using DSM-IV (43%), ICD-10 (32%) and both DSM-IV and ICD-10
      (12%). Mean age of awareness of a problem was 5.1 years, suggesting an average
      delay of approximately 4 years between awareness and diagnosis of ADHD. Baseline
      ADHD rating scale scores (physician-rated) indicated moderate to severe ADHD.
      Parent-rated SDQ scores were in agreement and suggested significant levels of co
      existing problems. CGI-S, CGAS and CHIP-CE scores also indicated significant
      impairment. Patients were offered the following treatments after the initial
      assessment: pharmacotherapy (25%), psychotherapy (19%), combination of
      pharmacotherapy and psychotherapy (25%), other therapy (10%) and no treatment
      (21%). CONCLUSION: The ADORE study shows that ADHD is similarly recognised across
      10 European countries and that the children are significantly impaired across a
      wide range of domains. In this respect, they resemble children described in
      previous ADHD samples.

PMID- 17177016
TI  - Cross-cultural reliability and validity of ADHD assessed by the ADHD Rating Scale
      in a pan-European study.
AB  - OBJECTIVES: To provide psychometric information on the Attention
      Deficit/Hyperactivity Disorder (ADHD) Rating Scale-IV (ADHD-RS-IV) in a large
      population of children with ADHD. METHODS: Patients aged 6-18 years (n=1,478 in
      baseline analysis) were rated by 244 physicians on the ADHD-RS-IV based on a semi
      structured interview with the patient's parent. Physicians additionally rated
      functional impairment (CGAS) and health status (CGI-S), and parents rated their
      child's behavioural and emotional problems (SDQ) and quality of life (CHIP-CE).
      RESULTS: Inattention and hyperactivity-impulsivity as dimensions of ADHD were
      replicated. 3-factor solutions reflecting the ICD-10 definition, with
      hyperactivity, impulsivity and inattention as separate dimensions were extracted
      in some national sub-samples and in separate analyses for boys and younger
      children.Good internal consistencies, strong country effects and small effects of
      age were found. Based on ADHD-RS-IV, 88.5% of patients met the criteria for any
      ADHD diagnosis. Correlations between ADHD-RS-IV and measures of functional
      impairment were low but statistically significant. The correlations with SDQ and
      CHIP-CE scales confirm the convergent and divergent validity of ADHD-RS-IV.
      CONCLUSIONS: Impressive evidence for the cross-cultural factorial validity,
      internal consistency as well as convergent and divergent validity of ADHD-RS-IV
      was found. ADHD can be assessed reliably and validly in routine care across
      Europe. The ICD-10 3-factor model seems to be less robust than the DSM-IV 2
      factor model, but may be a good description for special populations (boys,
      younger children).

PMID- 17177017
TI  - Psychopathological screening of children with ADHD: Strengths and Difficulties
      Questionnaire in a pan-European study.
AB  - OBJECTIVE: To examine the psychometric properties of the Strengths and
      Difficulties Questionnaire (SDQ) parent version and to determine the effects of
      age, gender, country and investigator type (paediatrician, child psychiatrist,
      other physician) on the SDQ scores in the prospective, non-interventional ADORE
      study. METHODS: The SDQ was completed for 1,459 children with ADHD (aged 6-18
      years) in 10 European countries. RESULTS: Factor analysis provided an exact
      replication of the original 5-factor SDQ subscale structure. All subscales were
      sufficiently homogeneous. The mean total difficulties and SDQ subscale scores of
      the ADORE sample clearly differed from UK normative data. Younger children were
      more impaired on different SDQ scales than older children, and girls were more
      emotionally affected than boys. Differences between countries were found for each
      SDQ scale, but the investigator type had no significant effect. Correlation
      coefficients between SDQ scales and other scales used in ADORE ranged from low
      (r<0.30) to high (r>0.50). CONCLUSIONS: The present study confirmed the validity
      and reliability of the parent-reported SDQ scale structure and showed that the
      scale scores are dependent on age and gender. In contrast to investigator type,
      different cultures had a significant effect on SDQ scores. Correlations with
      other scales used in the ADORE study underline both separate domains and
      meaningful associations.

PMID- 17177018
TI  - Validity of the health-related quality of life assessment in the ADORE study:
      Parent Report Form of the CHIP-Child Edition.
AB  - OBJECTIVES: To examine the cross-sectional reliability and validity of the Parent
      Report Form of the Child Health and Illness Profile-Child Edition (CHIP-CE), a
      generic measure of health-related quality of life (HRQoL), in children with ADHD
      in the pan-European ADHD Observational Research in Europe (ADORE) study. METHODS:
      Parents of children with ADHD (aged 6-18 years) in 10 European countries
      completed the CHIP-CE at the baseline visit (n=1,477; data missing for one
      patient). Analyses included determination of internal consistency reliability,
      ceiling and floor effects, factor analysis, and Pearson's correlations between
      CHIP-CE and other scales used to measure ADHD severity, problems and family
      strain. RESULTS: Internal consistency reliability was good-to-excellent
      (Chronbach's alpha>0.70) for all CHIP-CE domains and subdomains, and almost no
      ceiling and floor effects were observed. Factor analysis of the subdomains
      yielded a 12-factor solution. The domainlevel factor analysis identified six
      factors, the four domains of Satisfaction, Comfort, Resilience and Risk
      Avoidance. The two subdomains of Achievement domain, Peer Relations and Academic
      Performance, were separate factors in this sample. There were moderate-to-high
      correlations between the CHIP-CE scales and measures of ADHD and family factors.
      The HRQoL of children in ADORE was dramatically lower than that of community
      youth,with mean CHIP-CE scores almost 2 standard deviations below community
      norms. CONCLUSIONS: The validity and reliability of CHIP-CE to measure HRQoL in
      children with ADHD across Europe was confirmed.

PMID- 17177019
TI  - The Family Strain Index (FSI). Reliability, validity, and factor structure of a
      brief questionnaire for families of children with ADHD.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) in children affects
      every member of the family. Practical tools are needed to assess the effects of
      ADHD on families to better understand and address the level of stress, strain and
      burden that families experience. OBJECTIVE: To provide the preliminary
      reliability, validity and factor structure of the Family Strain Index (FSI), a 6
      item parent-report questionnaire. METHODS: The FSI was completed by 1,477 parents
      of children with ADHD (aged 6-18 years) at the baseline visit of the ADORE study
      in 10 European countries (data missing for one patient). RESULTS: The FSI taps
      into an overall experience of worry and interruptions of activities in families
      of children with ADHD, as a single factor was identified with excellent internal
      consistency (alpha=0.87). Despite its brevity, almost no ceiling (worst score) or
      floor (best score) effects were observed for families of these highly symptomatic
      children. This score distribution and the 5-point response options suggest that
      the FSI will be responsive to changes in the experience of family strain
      associated with children's ADHD treatment. CONCLUSION: The ease of completion and
      coherence of the underlying construct indicates that the FSI may be a practical
      clinical tool for monitoring changes in family strain associated with children's
      ADHD treatment.

PMID- 17177020
TI  - Molecular diversity of microbial community in acid mine drainages of Yunfu
      sulfide mine.
AB  - Two acid mine drainage (AMD) samples were studied by a PCR-based cloning
      approach, which were from Yunfu sulfide mine in Guangdong province, China. A
      total of 15 operational taxonomic units (OTUs) were obtained from the two AMD
      samples. The percentage of overlapped OTUs in two AMD samples was 42.1%.
      Phylogenetic analysis revealed that the bacterium in the two samples fell into
      four putative divisions, which were Nitrospira, alpha-Proteobacteria, beta
      Proteobacteria, and gamma-Proteobacteria four families. Organisms of genuses
      Acidithiobacillus and Gallionella, which were in gamma-Proteobacteria family and
      beta-Proteobacteria family, respectively, were dominant in two samples. The
      proportions of clones affiliated with Gallionella in each sample were 47.2% (G2)
      and 16.9% (G1). The result suggested that organisms of Gallionella were a very
      important composition in microbial communities of the two AMD samples we studied.
      In addition, the PCR amplification of archaeal 16S rDNA genes form these two AMD
      samples have been performed with two sets of archaea-specific primers, but no PCR
      product found.

PMID- 17177021
TI  - Cauda equina syndrome presentation of sacral insufficiency fractures.
AB  - INTRODUCTION: Sacral insufficiency fractures are a well recognised cause for low
      back, buttock and groin pain in the elderly. However, over a 4 year period, four
      patients have presented with symptoms of cauda equina syndrome, who were found on
      investigation to have acute sacral insufficiency fracture without any other
      aetiological spinal abnormality. PATIENTS AND METHOD: Four patients who presented
      to the spinal surgeons of our institution with symptoms of cauda equina syndrome
      were referred for spinal MR. Sagittal and axial T1 and T2 weighted turbo spin
      echo sequences of the lower thoracic and lumbar spine were performed on all
      patients. Subsequent studies included MR of the sacrum supplemented where
      appropriate by CT and technetium MDP bone scintigraphy. RESULTS: No evidence of a
      compressive lesion of the lower thoracic or lumbar spine was present in any of
      the four patients. Dedicated MR examination of the sacrum in these patients
      revealed unilateral acute insufficiency fractures involving zone 1 from S1 to S3
      extending from the sacro-iliac joint to the lateral margin of the sacral foramen.
      There was no evidence of compression of the sacral nerve roots. The possible
      mechanism for the symptomatic presentation is discussed. CONCLUSION: Sacral
      insufficiency fractures should be excluded in elderly or osteoporotic patients
      presenting with cauda equina syndrome who have no evidence of compression in the
      thoraco-lumbar MR studies.

PMID- 17177022
TI  - Distal intersection tenosynovitis of the wrist: a lesser-known extensor
      tendinopathy with characteristic MR imaging features.
AB  - OBJECTIVE: To present the MRI imaging findings of extensor tenosynovitis at the
      distal intersection or crossover between the second (extensor carpi radialis
      longus (ECRL) and brevis (ECRB)) and third (extensor pollicis longus (EPL))
      extensor compartment tendons, and the anatomical details that may play a role in
      the pathogenesis of this condition. DESIGN AND PATIENTS: The imaging studies and
      clinical records of five patients (three females and two males, with ages ranging
      between 22 and 78 years; mean age, 49 years) presenting with pain on the dorsal
      and radial aspect of the wrist were reviewed by two musculoskeletal radiologists
      in consensus. Three cases were identified serendipitously during routine clinical
      reading sessions; a follow-up computerized database search for additional cases
      reported in the prior two years yielded two additional cases. The overall number
      of cases screened was 1,031. The diagnosis of tendinopathy affecting the second
      and third compartment extensor tendons was made on the basis of MRI findings and
      clinical follow-up, or synovectomy. RESULTS: All patients showed signs of
      tenosynovitis: in four patients both the tendons of the second and third extensor
      compartments were affected; the fifth patient showed signs of tenosynovitis of
      the EPL tendon, and tendinosis of the extensor carpi radialis tendons. Three
      patients showed tenosynovitis proximal and distal to the point of intersection;
      and in two of them, a discrete point of constriction was appreciated at the
      crossover site in relation to the extensor retinaculum. Two patients showed
      tenosynovitis limited to the segment distal to the point of decussation.
      Tendinosis tended to follow the presence of tenosynovitis. In one of the
      patients, subtendinous reactive marrow edema in Lister's tubercle was noted.
      CONCLUSION: Distal intersection tenosynovitis may be related to the biomechanical
      pulley effect exerted by Lister's tubercle on the EPL tendon as it leaves the
      third compartment and crosses over the extensor carpi radialis tendons, as well
      as the constraining effect of the extensor retinaculum. These anatomical features
      determine the presence of characteristic MR imaging findings.

PMID- 17177023
TI  - Spontaneous regression of osteochondromas.
AB  - Spontaneous regression of an osteochondroma is an infrequent event. In this
      report, two cases with spontaneous regression of osteochondromas are presented.
      The first case was a solitary osteochondroma of the pedunculated type involving
      the right proximal humerus in a 7-year-old boy. This lesion resolved over 15
      months of observation. The second case was a 3-year-old girl with multiple
      osteochondromatosis, in whom sessile osteochondromas of the right tibia and left
      fibula regressed over 33 months. The mechanism of this phenomenon is discussed
      with a review of previous reports. Regarding treatment, careful observation may
      be acceptable for typical osteochondromas, especially in young children.

PMID- 17177024
TI  - Chymostatin can combine with pepstatin to eliminate extracellular protease
      activity in cultures of Aspergillus niger NRRL-3.
AB  - Aspergillus strains are being considered as potential hosts for recombinant
      heterologous protein production because of their excellent extracellular enzyme
      production characteristics. However, Aspergillus proteases are problematic in
      that they modify and degrade the heterologous proteins in the extracellular
      medium. In previous studies we observed that media adjustments and maintenance of
      a filamentous morphology greatly reduced protease activity and that a low
      concentration of the aspartic protease inhibitor pepstatin inhibited the latter
      protease activity to the extent of approximately 90%. In this paper we report
      that when the serine protease inhibitor chymostatin is used in combination with
      pepstatin 99-100% of total protease activity in Aspergillus cultures is
      inhibited. In protease assays a concentration of 30 microM chymostatin combined
      with 0.075 microM pepstatin was required for maximum inhibition. Inhibitor
      concentrations of chymostatin and pepstatin of 120 and 0.3 microM, respectively,
      when added to Aspergillus cultures, has no significant effect on biomass
      production, glucose utilization or culture pH pattern. The potential of using
      these protease inhibitors in cultures of recombinant Aspergillus strains
      producing heterologous proteins will now be investigated to determine if the
      previously observed recombinant protein denaturing effects of Aspergillus
      proteases can be negated.

PMID- 17177025
TI  - Immunohistochemical analysis of growth mechanisms in juvenile nasopharyngeal
      angiofibroma.
AB  - Angiogenic factors are discussed to participate in growth and promotion of
      juvenile nasopharyngeal angiofibroma (JNA). However, only few data are available
      and mechanisms remain unclear. In the presented study we analysed the expression
      and subcellular distribution of several angiogenic growth factors and receptors
      potentially involved in JNA-growth and -vascularisation. In a retrospective,
      descriptive, multicenter-study, we analysed 13 formalin-fixed, paraffin-embedded
      or cryopreserved JNA-tumors (eleven primary tumors and two recurrent ones) after
      immunohistochemical staining. We used monoclonal antibodies specific for
      transforming growth factor beta 1 (TGF-beta(1)), basic fibroblast growth factor
      (bFGF), the VEGF-receptors 1 and -2 (FLT-1 and FLK-1), and the hypoxia inducible
      factor (Hif-1alpha). Data were compared to the vessel density. Quantitative
      analysis of staining intensities was performed by a computer assisted
      quantification technique. Endothelial and stromal compartments of the samples
      were analysed separately. Data were compared to vessel densities and patients
      data. The VEGF-Receptor-2 (FLK) was frequently unregulated in the stroma and
      endothelium of those samples with high vessel densities. Similarly, we observed
      high bFGF- and TGF-beta(1) levels in the stroma of strong vascularised samples.
      No correlations of expression levels to patients' data were found. The reported
      data support the concept of JNA-growth and -vascularisation driven by factors
      released from stromal fibroblasts. Therefore, inhibition of these factors might
      be beneficial for the therapy of inoperable JNA.

PMID- 17177026
TI  - FDG PET and PET/CT for the detection of the primary tumour in patients with
      cervical non-squamous cell carcinoma metastasis of an unknown primary.
AB  - In patients with a neck metastasis from an unknown primary with non-squamous cell
      cancer (non-SCC) histology, the primary is often located outside the head and
      neck area. We retrospectively evaluated 326 patient records and found 14 patients
      with non-SCC neck lymph node metastasis from an unknown primary undergoing whole
      body F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) with or
      without coregistered computed tomography (PET/CT). The PET or PET/CT findings
      were verified by pathological work-up, additional imaging tests, and clinical
      follow-up. PET detected pathological FDG uptake suspicious for the primary in
      eight patients. PET or PET/CT findings were true positive in seven patients, true
      negative in 4, false positive in 1, and false negative in two patients. In one
      patient PET/CT revealed a synchronous ovarian carcinoma. The results suggest that
      whole body imaging with FDG PET and PET/CT can be useful to identify unknown
      primaries of non-SCC origin. However, the work-up of patients undergoing PET or
      PET/CT in our study was very heterogeneous and the primary was more likely found
      in patients without extensive imaging before PET scanning. Further studies should
      evaluate if the histology of a neck nodal metastasis should influence the choice
      of the imaging method and the role of PET and PET/CT imaging for the work up of
      patients with a non-SCC neck lymph node metastasis of an unknown primary.

PMID- 17177028
TI  - Early post partum discharge: is it possible?
AB  - OBJECTIVES: To characterize maternal post partum complications and to identify
      risk factors for the development of post partum complications in low risk
      parturients. STUDY DESIGN: The first part of our research was a case study only.
      It included low risk parturients identified using a computerized database who
      developed post partum complication between the years 2000 and 2003 (n = 136). The
      second part of the study was in a case-control format. The control group
      consisted of low risk parturients who gave birth during the same time period and
      did not develop post partum complications (n = 31,211). RESULTS: Fever was the
      most common complication (36%) identified, with a mean delivery to complication
      time of 31.1 h. Excessive vaginal bleeding (22%) was diagnosed earlier, with a
      mean delivery to complication time of 4.2 h. The risk factors for complications
      identified were the following: first delivery, fifth delivery or more and
      cesarean delivery in the past (P = 0.009 and 0.002, respectively). CONCLUSION:
      The results of this study support the possibility of early discharge for women in
      a predefined low-risk group. Most of the complications that may occur after
      discharge do not pose an immediate threat and afford the patient enough time to
      safely reach the hospital. Most of the complications in a low risk parturient
      group occur within 6 h post partum and may allow consideration of an early
      discharge policy.

PMID- 17177027
TI  - Methylation profile in benign, borderline and malignant ovarian tumors.
AB  - PURPOSE: Promoter hypermethylation is a common phenomenon in neoplasm. The aims
      of this study were (a) to compare the methylation profiles in different types of
      ovarian tumors and (b) to determine the possible relationship between the
      methylation status and different clinicopathologic characteristics. METHODS: We
      examined the promoter methylation status of 9 tumor suppressor genes (RARbeta2,
      TMS1, RIZ1, P15, P16, PTEN, MINT31, APC and HIC1) in 89 ovarian cancers, 16
      borderline ovarian tumors, 19 benign ovarian tumors, 16 normal ovarian tissue and
      5 ovarian cancer cell lines. The methylation status was examined with respect to
      clinicopathologic characteristics of the ovarian cancer patients. RESULTS:
      Methylation indices for ovarian cancer, borderline ovarian tumor, benign ovarian
      tumor, normal ovarian tissue and ovarian cancer cell lines were 28.8, 20.1, 10.5,
      11.8 and 42.2%, respectively. It was significantly higher in ovarian cancer,
      borderline ovarian tumor and ovarian cancer cell lines (X (2) test, P < 0.001, P
      = 0.01 and P < 0.001, respectively) than benign or normal ovarian tissues. In
      ovarian cancer, concurrent methylation of at least two genes (CM2) was associated
      with early stage disease (X (2) test, P = 0.035) and less recurrence (X (2) test,
      P = 0.020). When the methylation statuses of the nine genes as well as CM2 were
      included in multivariate Cox Regression analysis, CM2 was the only independent
      predictor for survival (P = 0.013). CONCLUSION: CM2 was an independent predictor
      for survival in ovarian cancer.

PMID- 17177029
TI  - Spontaneous resolution of cystic hygroma in 47,XYY fetus.
AB  - INTRODUCTION: 47,XYY karyotype occurs in 1 out of 1,000 male births. Physical
      phenotype is normal, with tall stature by adolescence. Prenatal diagnosis of the
      47,XYY syndrome is usually fortuitous. Some cases are being diagnosed when
      prenatal karyotyping is done for the detection of Down syndrome and other major
      aneuploidies. Some cases are diagnosed when prenatal ultrasonographic findings of
      fetal abnormalities are found. Herein, we report a case of 47,XYY after prenatal
      finding of fetal cystic hygroma with spontaneous resolution. CASE REPORT: A 19
      year-old primigravid woman presented for antenatal care at the 13th week of
      pregnancy. She used oral isotretinoin, being unaware of pregnancy, for a
      treatment of acne during the first 4 weeks of gestation. Ultrasonogram was
      performed due to first trimester screening and the history of isotretinoin
      exposure. The result revealed a single viable fetus compatible with a 13-week
      pregnancy and a posterior cervical cystic hygroma. No other structural anomalies
      were noted. An amniocentesis was performed for prenatal chromosome analysis and a
      47,XYY karyotype was found. Repeated ultrasonogram at 23-week gestation showed
      that the cystic hygroma had spontaneously disappeared. She delivered a normal
      appearing male infant by spontaneous vaginal delivery at 40 weeks. The maternal
      and neonatal outcomes were uneventful. CONCLUSION: Fetal cystic hygroma can be
      associated with abnormal karyotype, such as 47,XYY. Without hydrops fetalis, this
      may be ended with a normal outcome. Therefore, an antenatal karyotype
      determination should be offered to any woman whose fetus has cystic hygroma, even
      to those with spontaneous resolution.

PMID- 17177030
TI  - Successful outcome after hepatic rupture in previous eclamptic pregnancy.

PMID- 17177031
TI  - Spontaneous regression in recurrent epithelial ovarian cancer.
AB  - BACKGROUND: Although spontaneous regression has been reported in several cancers,
      it is generally believed that this rare phenomenon does not occur in epithelial
      ovarian cancer. CASE: We presented a stage IV epithelial ovarian cancer patient
      with long-term disease-free survival after palliative local irradiation alone
      against recurrence. The recurrent supraclavicular lymph node was almost
      completely necrotic, and the swelling of the para-aortic lymph node spontaneously
      regressed. CONCLUSION: The histologic features and unexpected clinical course in
      this patient strongly suggest that spontaneous regression occurred in recurrent
      epithelial ovarian cancer.

PMID- 17177032
TI  - [Systemic treatment of liver and biliary tumors].
AB  - Hepatocellular carcinoma (HCC) is generally difficult to treat. This is primarily
      due to the reduced liver function of most patients and the low sensitivity of
      liver cancer cells to chemotherapy. This has been demonstrated in many clinical
      trials. Molecular therapies might represent an improvement in the systemic
      treatment of patients with HCC. In addition to anti-angiogenic drugs, compounds
      which interfere with specific signal transduction cascades have shown promising
      results in smaller trials. There are only limited numbers of studies about the
      systemic treatment options for biliary cancers. To date, the best response rates
      have been achieved with combination chemotherapies containing platinum analogues
      and gemcitabine. In the absence of larger clinical phase III trials, no standard
      chemotherapy for biliary cancers exists today.

PMID- 17177033
TI  - [Pulmonary diseases and heart function].
AB  - The most severe cardiac sequel to lung disease is the load on the right ventricle
      due to pulmonary hypertension with the development of a cor pulmonale. This is
      characterized by hypertrophy and/or dilatation of the right ventricle because of
      a primary impairment of lung function and/or lung structure. The most important
      pathomechanisms for the development of pulmonary hypertension are vessel
      obliteration, mechanical lesions, primary vascular or extra-vascular inflammation
      and hypoxic vasoconstriction. Chronic obstructive pulmonary disease (COPD) is one
      of the most important reasons for chronic cor pulmonale. A further very common
      reason is obstructive sleep apnea syndrome, especially if combined with a COPD.
      In this case, the prevalence of cor pulmonale can reach 80%. The development of a
      chronic cor pulmonale is the most striking negative prognostic factor for these
      patients. Only 30% of COPD patients with cor pulmonale survive longer than 5
      years, and only early detection of the disturbances to respiration which might
      potentially lead to cor pulmonale and their subsequent therapy are able to
      improve the patient's prognosis. Furthermore, pulmonary diseases may also have an
      impact on the left heart side in terms of an impairment of left heart function or
      by inducing severe arrhythmias . Thus, lung diseases may have both a significant
      impact on right and left heart performance.

PMID- 17177034
TI  - [Angina pectoris and ST-elevation after chemotherapy with 5-fluorouracil].
AB  - We report on the case of a 64 year old male who received chemotherapy for a
      metastatic squamous cell carcinoma of the oropharynx. The chemotherapeutic
      regimen consisted of 5-fluorouracil (5-FU) and cisplatin. Six hours after
      completion of the first 24 h continuous infusion of 5-FU, the patient developed
      severe chest pain accompanied by vegetative symptoms and a pronounced ST
      elevation of the precordial leads. Under the suspicion of an acute anterior
      myocardial infarction an immediate coronary angiogram was performed,
      demonstrating a total occlusion of the left anterior descending (LAD) coronary
      artery close to the left main stem. The other coronary arteries appeared smooth.
      After the intracoronary administration of nitroglycerine, the LAD reopened
      spontaneously without any residual stenosis, paralleled by complete relief of all
      symptoms. Therefore, 5-FU induced coronary spasm was diagnosed. After initial
      therapy with intravenous nitrate followed by oral calcium channel blocker, the
      patient remained free of symptoms and no rise in cardiac enzymes were noted. The
      chemotherapeutic regimen was changed to cisplatin plus docetaxel. No new attacks
      of chest pain occurred and the antivasospastic therapy could be stopped without
      further events.

PMID- 17177035
TI  - Corneal ectasia after photorefractive keratectomy.
AB  - BACKGROUND: Corneal ectasia after photorefractive keratectomy (PRK) has only been
      occasionally reported, and its incidence has not been assessed. METHODS: In a
      retrospective, non-comparative case series, incidence of corneal ectasia was
      evaluated in a personal consecutive 6453-case series of myopic PRK with a minimum
      follow-up of 18 months. Features and prognosis were evaluated in all patients
      with ectasia after PRK (in both personal and referred cases). RESULTS: Ectasia
      was detected in three eyes of two patients (patients 1 and 2) 3 years and 1 year
      after PRK performed elsewhere. In addition, in the personal PRK series, two eyes
      of two patients (patients 3 and 4) developed corneal ectasia 5 months after
      surgery (incidence: 0.03%). Pre-operatively, forme fruste keratoconus was present
      in patients 1, 3 and 4; keratoconus in the fellow eye in patient 2; pachymetry
      <500 micron in patients 2 and 3. In patient 1, rigid contact lenses were
      prescribed, and in patient 2 deep anterior lamellar keratoplasty was needed; in
      patients 3 and 4, low induced astigmatism resulted, requiring driving spectacles
      in patient 3. CONCLUSIONS: PRK induced corneal ectasia in predisposed eyes, even
      after low myopic ablations. Forme fruste keratoconus and keratoconus in the
      fellow eye were the main pre-operative findings. Prognosis varies according to
      severity.

PMID- 17177036
TI  - Loss of vision due to a physiologic pituitary enlargement during normal
      pregnancy.
AB  - BACKGROUND: Physiologic pituitary enlargement during normal pregnancy is well
      known, but we are unaware of previous reports on a natural course of visual loss
      due to this disease. METHODS: A 30-year-old woman presented blurred vision in the
      left eye from the 30th week of pregnancy. At 38 weeks visual acuity was 0.9 in
      the left eye. Automated perimetry revealed a mild central visual defect in the
      left eye. A magnetic resonance imaging (MRI) scan revealed pituitary enlargement
      with compression of the anterior optic chiasm. We observed the natural course of
      this case. RESULTS: At 16 weeks after delivery, visual acuity was 1.5 in both
      eyes with normal visual field, and an MRI scan revealed a normal-sized pituitary
      without compression of the optic chiasm. CONCLUSIONS: Ophthalmologists should be
      aware of visual loss by physiologic pituitary enlargement to avoid unreasonable
      neurosurgical procedures.

PMID- 17177038
TI  - Cell culture conditions affect RPE phagocytic function.
AB  - BACKGROUND: Changes in the phenotype of retinal pigment epithelium (RPE) cells in
      vitro are associated with medium conditions and changes in function. Main goals
      in RPE tissue engineering are cell propagation in serum-free defined culture
      conditions, resulting in cells exhibiting differentiated morphology and
      functioning in vitro. METHODS: To compare the effects of various media and
      supplements on cell function, an optimized high-throughput phagocytosis assay was
      developed. Adult human SV40-RPE cells were cultured. Test media included: MEM(E),
      DMEM, F99, SFM and hSFM, with or without supplements. SNAFL-2 labelled OS were
      added to RPE in vitro for 4 h and phagocytic binding and uptake were measured.
      RESULTS: RPE phagocytosis was of different magnitude depending on the serum-free
      basic cell culture media in the following order: hSFM, SFM > DMEM, MEM > F99.
      Choroid-conditioned medium (ChCM) decreased phagocytosis dose dependently.
      Whereas 1% retinal extract (RE) supplementation increased, higher concentrations
      decreased phagocytosis. Addition of 10% FCS increased phagocytosis. 15% ChCM
      quenched the stimulation induced by 10% FCS, an effect which could be reversed by
      the addition of 1% RE. CONCLUSIONS: Cell culture media and RPE environmental
      factors exert substantial and differential alteration of RPE phagocytic ability.
      Phagocytosis in a serum-free defined medium is superior to unsupplemented basic
      media, but still differs from serum-supplemented media (F99RPE) designed for cell
      propagation. We conclude that media SFM or hSFM promoted phagocytosis most, and
      application of FCS or 1% RE supports phagocytosis. Unknown factors from
      neighbouring tissues (retina and choroid) affect phagocytosis differently,
      suggesting a role in retinal pathogenesis. The results will support
      identification of specific environmental factors and facilitate design of cell
      culture media.

PMID- 17177039
TI  - Dynamic contour tonometry (DCT) versus Goldmann applanation tonometry (GAT) - a
      comparison of agreement and reproducibility.
AB  - BACKGROUND: The PASCAL dynamic contour tonometer (DCT) is a novel device designed
      for intraocular pressure (IOP) measurements. It is assumed to be largely
      independent of corneal properties. In a previous study we compared DCT with
      Goldmann applanation tonometry (GAT) in 100 right eyes with normal corneas. The
      aim of the present study is to evaluate whether differences DCT-GAT >or= 2.0 mmHg
      found in the previous study are reproducible and also present in the fellow eye.
      METHODS: Twenty-three of the 100 patients (M:F = 8:15, mean age: 36 +/- 11 SD,
      range 22-53 years) with a previous difference DCT-GAT >or= 2.0 mmHg were included
      in the present study. The minimum interval between the initial and the current
      examination was 3 weeks. The IOP-values of the fellow eyes in this subgroup were
      assessed in parallel. RESULTS: The difference DCT-GAT was 2.44 +/- 0.4 SEM mmHg
      in the subgroup of the 23 right eyes and 2.03 +/- 0.5 SEM mmHg for the fellow
      eyes, compared to 0.94 +/- 0.5 SEM mmHg in the initial sample of 100 eyes.
      CONCLUSIONS: In cases with higher difference between DCT-GAT, the difference is
      reproducible and even present in the fellow eye. We, therefore, assume that the
      differences are not caused by chance, but by differing biomechanical corneal
      properties.

PMID- 17177040
TI  - The impact of an educational DVD on cancer patients considering participation in
      a phase I clinical trial.
AB  - GOALS OF WORK: The quality of informed consent in phase I trials is
      controversial, partially due to gaps in patient understanding. We assessed an
      educational DVD's impact on knowledge and satisfaction in cancer patients newly
      referred to a phase I clinic. MATERIALS AND METHODS: Forty-nine patients were
      randomly assigned to view an educational DVD (n = 22) which explained phase I
      trials or a placebo DVD (n = 27). Patients completed a questionnaire assessing
      knowledge of phase I studies and satisfaction with the DVD. The blinded
      interviewing physician (n = 8) rated the patient's understanding of phase I
      trials. MAIN RESULTS: The mean patient age was 56; 61% were male. Patients who
      viewed the educational DVD were less likely to believe that phase I trials
      determine drug efficacy (p = 0.019), more likely to know that phase I drugs have
      not been thoroughly studied in humans (p = 0.003), and less likely to believe
      that these agents have proven activity against human cancers (p = 0.008). More
      patients who viewed the educational DVD agreed/strongly agreed that the DVD
      provided useful information (p < 0.001), were confident in their knowledge of
      phase I trials (p = 0.031), felt aided in their decision to enter a phase I study
      (p = 0.011), and would have more questions for their physicians because of the
      DVD (p = 0.017). No statistically significant difference in physician perception
      of patient understanding or phase I trial accrual was observed between the
      educational and placebo DVD groups. CONCLUSIONS: An educational DVD increased
      patient knowledge and satisfaction regarding participation in phase I clinical
      trials.

PMID- 17177041
TI  - Social support among women who died of ovarian cancer.
AB  - GOALS OF WORK: We investigated the effects of social support in the last 6 months
      of life for women who died of ovarian cancer. MATERIALS AND METHODS: The study
      population included women enrolled in one of three Managed Care Organizations who
      died of ovarian cancer (1995-2000). Information was collected on demographics,
      living environment, presence of escorts to oncology encounters, comorbidities,
      medications, outpatient and inpatient encounters, and referrals to home health
      and hospice. Two characteristics of social support were examined: living with
      others and being escorted to one or more oncology visits. RESULTS: Of 421
      subjects, both aspects of social support were known for 345 (82%). Of these, 227
      (66%) lived with others and were escorted, 33 (10%) lived with others but were
      never escorted, 59 (17%) lived alone but were escorted, and 26 (8%) lived alone
      and never were accompanied. Women living alone were less likely to be taking a
      psychotropic medication (57% vs 70%, p = 0.021) and were somewhat less likely to
      receive hospice referral (42% vs 53%, p = 0.054). Women who were never escorted
      had fewer outpatient encounters (12.60 vs 15.77, p = 0.033) and were less likely
      to be referred to home health (18% vs 30%, p = 0.046). CONCLUSIONS: This study
      indicates that social support has some beneficial effects on receipt of personal
      health services. Friends and family may act as proponents for the patient in
      obtaining services. Health care professionals should be encouraged to assess the
      cancer patient's social situation and identify areas where help may be needed.

PMID- 17177042
TI  - [Corrective osteotomy of post-traumatic malunions and pseudarthroses in the femur
      using a fork plate: a prospective analysis of 23 consecutive cases].
AB  - INTRODUCTION: The fork plate is a further development of the AO fixed-angle blade
      plate, which facilitates the seeding of the angle blade. In a prospective study
      we evaluated the applicability of the fork plate for the correction of post
      traumatic malunions and pseudarthroses in the femur. MATERIAL AND METHODS:
      Between 01/1993 and 12/2003 a consecutive series of 23 patients were operated due
      to post-traumatic malunion or pseudarthrosis of the femur with an average age of
      46 years at the time of surgery. The operative procedure is analogous to the one
      using angle blade plates. The most important surgical step, the placement of the
      fork instead of the blade, is more precise thanks to stepwise control with the
      image intensifier. RESULTS: All preexisting malunions and pseudarthroses were
      corrected with the fork plate as preoperatively planned. Complications not
      related to the implant were found in 13%, all of which resolved without sequelae.
      In 87% we found a bony union of the osteotomy after 3 months, and the three
      remaining femora healed within an additional 2-12 months without loss of the
      correction achieved. CONCLUSION: In all of the cases analyzed, the fork plate
      proved to be of value for correction of femoral malunion and pseudarthrosis. In
      relation to the angle blade plate, the fork plate features a modified surgical
      technique with the same possible indications. As a consequence this modification
      provides a high level of therapeutic safety even with a small number of annual
      operations performed.

PMID- 17177043
TI  - [Cost-benefit analysis of intraoperative 3D imaging].
AB  - BACKGROUND: With intraoperative 3D imaging, inevitable corrections may be done
      already during the operation, and a second procedure can be avoided. The purpose
      of this study was to perform a cost-benefit analysis during the first year of
      intraoperative 3D application in order to provide a cost transparency for the
      surgeon within the current DRG system. METHODS: On the basis of internal data and
      the literature, the annual operating costs of the ISO-C(3D) were calculated at
      27,940 euros (purchase price, depreciation, maintenance, repair), the costs of an
      average revision as a secondary operation at 2,385 euros (costs avoided with the
      ISO-C(3D), Siremobil, Siemens, Erlangen, Germany), and the dynamic costs of an
      intraoperative 3D scan were averaged to 131.08 euros (draping, additional time,
      personnel). RESULTS: In the year 2003 intraoperative 3D scanning was done in 126
      patients, and intraoperative revision was performed in 24 (19%) due to the
      additional intraoperative 3D information provided by the Siremobil. In 11 (8.7%)
      patients the implant position was corrected and in 13 (10.3%) patients the
      reduction was improved. Taking only fixed costs into consideration, 29,311.52
      euros could be saved, and when fixed and dynamic costs are taken into account
      12,795.44 euros could be saved. Since the parameters for each hospital are
      different, the following formula for an individual computation is suitable. For
      the calculation of the cost the following mathematical relationship results:
      (annual fixed costs) + (costs per scan x number of cases) - (revision costs x
      revision rate [p]) x number of cases [N]) = 0. DISCUSSION: Although the costs of
      an ISO-C(3D) are considerably high, an economic benefit can also accrue with
      frequent application and high rates of avoided revision. However, if the rate of
      avoided revision adds up to only 5%, a substantial deficit may result.

PMID- 17177044
TI  - [Comparison of C-arm CT and standard imaging in osteosyntheses of fractured
      distal radius specimens].
AB  - BACKGROUND: The purpose of this study was to evaluate the value of C-arm CT
      imaging of the distal radius with standard patient positioning in intraoperative
      assessment of plate osteosynthesis. MATERIALS AND METHODS: Four complete distal
      radius specimens from human cadavers were fractured (type C), and internal
      fixation with palmar plates (stainless steel) was then carried out in each. On
      the basis of C-arm fluoroscopy, radiography and C-arm CT (Siremobil Iso-C3D,
      scans with forearm bones positioned parallel to the z-axis), 19 observers
      subsequently evaluated the positions of screws near the joint and any steps
      within the joint, after which the bones were surgically exposed and the imaging
      results checked against direct visual observations. RESULTS: No statistically
      significant differences were detected either between the modalities or between
      the evaluator groups. CONCLUSION: With standard patient positioning, the
      performance of C-arm CT was equivalent to and not better than that of current
      standard procedures, i.e. intraoperative fluoroscopy and postoperative
      radiography. Further studies should examine whether this holds true in clinical
      practice with representative patient collectives when titanium implants are used
      and/or optimized patient positioning is practised.

PMID- 17177046
TI  - Pulmonary bacterial co-infection in children ventilated for severe respiratory
      syncytial virus bronchiolitis is common.

PMID- 17177047
TI  - Steps for the implementation and validation of tight glucose control.

PMID- 17177045
TI  - [Oral cytology: historical development, current status, and perspectives].
AB  - Oral cytology has aroused new interest caused by introduction of the cytobrush as
      a sampling device and the use of additional analytical methods. By brushing it is
      possible to reach deeper layers of the oral mucosa where squamous intraepithelial
      neoplasia (SIN) begins. The biological potential of the oral epithelial cells
      obtained can be evaluated by the following additional methods: computer-assisted
      image analysis (OralCDx), DNA cytometry, immunohistochemistry, monolayer
      cytology, and molecular biological analysis. All of those methods can increase
      sensitivity (up to 100%) and specificity (up to 100%) of oral brush biopsy.
      Nevertheless, there are reports that oral epithelial carcinomas were not
      identified. No comparative study exists allowing conclusions to be drawn about
      the value of the single methods. Immunocytochemistry with commercial antibodies
      against laminin-5 is generally available and methodologically easy. Oral brush
      biopsy as a non invasive diagnostic method can be useful for the early detection
      of oral mucosal lesions. Positive findings or progression of the lesion despite
      negative findings are indications to refer the patient to a specialized clinic
      where a surgical biopsy should be performed, followed by histopathological
      analysis. Histopathology remains the gold standard for the definitive diagnosis
      of oral malignant lesions.

PMID- 17177048
TI  - Introduction and evaluation of a computerised insulin protocol.
AB  - OBJECTIVE: To lower glucose levels in all patients in the intensive care unit
      (ICU) to the target range of 4.5-7.5 mmol/l using a nurse-driven computerised
      insulin protocol in combination with bedside glucose measurement. DESIGN: Cohort
      study. SETTING: Mixed adult ICU. PATIENTS AND PARTICIPANTS: All 182 patients
      admitted to the ICU during a 3-month period were studied, except for 3 patients
      admitted for diabetic keto-acidosis. INTERVENTIONS: Five steps were taken to
      improve glucose regulation: (1) Nurses were authorised to adjust insulin dosage
      using a protocol. (2) Glucose was measured more often. (3) Glucose was measured
      at the bedside. (4) Consecutive protocols aimed for successively lower glucose
      levels; the final protocol had a target range of 4.5-7.5 mmol/l. (5) The protocol
      was computerised. MEASUREMENTS AND RESULT: Mean glucose decreased from 9.23
      mmol/l without protocol to 7.68 mmol/l with the final protocol. This final
      protocol with the target of 4.5-7.5 mmol/l was evaluated more extensively.
      Glucose levels were measured a total of 1854 times in 179 ICU admissions during
      552 ICU treatment days. The median glucose level was 7.0 mmol/l, and 53.1% of
      glucose measurements were within the target range of 4.5-7.5 mmol/l. One episode
      of hypoglycaemia (glucose </= 2.2 mmol/l) occurred, representing 0.5% of patients
      or 0.05% of glucose measurements. CONCLUSIONS: The combined strategy of
      successively more ambitious nurse-driven (computerised) insulin protocols and
      bedside glucose measurement resulted in acceptably low glucose levels with very
      few episodes of hypoglycaemia.

PMID- 17177050
TI  - Isolation and characterization of an antifungal peptide with antiproliferative
      activity from seeds of Phaseolus vulgaris cv. 'Spotted Bean'.
AB  - A 7.3-kDa antifungal peptide with an N-terminal sequence exhibiting remarkable
      homology to defensins from other leguminous plants was isolated from Phaseolus
      vulgaris cv. 'Spotted Bean'. The isolation procedure involved ion exchange
      chromatography on O-diethylaminoethyl (DEAE) cellulose, affinity chromatography
      on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel
      filtration by fast protein liquid chromatography on Superdex 75. The peptide was
      unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel and SP-Sepharose.
      It exerted an antifungal action on Fusarium oxysporum and Mycosphaerella
      arachidicola. It inhibited mycelial growth in F. oxysporum with an IC(50) value
      of 1.8 microM. It suppressed [methyl-(3)H]-thymidine incorporation by leukemia
      L1210 cells and MBL2 cells with an IC(50) value of 4.0 and 9.0 microM,
      respectively. There was no effect on HIV-1 reverse transcriptase activity when
      the peptide was tested up to 0.1 mM.

PMID- 17177049
TI  - Intensive care outcome of adult patients operated on for congenital heart
      disease.
AB  - OBJECTIVE: To describe the ICU outcome and the most frequent complications
      observed in adult patients operated on for a congenital heart disease. DESIGN AND
      SETTING: Retrospective analysis of prospectively collected data and chart review
      in an adult cardiovascular ICU of a university hospital. PATIENTS: 156 patients
      older than 15 years with congenital heart disease undergoing cardiac surgery
      between June 2001 and June 2005. RESULTS: According to the initial cardiac
      malformation, patients were divided in four groups with different operative risk
      based on the Euroscore: those diagnosed bicuspid aortic valve (n = 73) had a
      score of 5, those with tetralogy of Fallot (n = 33) 5.5, those with simple
      cardiac defect (n = 26) 3, and those with complex malformations (n = 24) 6. Only
      two patients (one with tetralogy of Fallot and one with complex malformations)
      died during the hospitalization (1.2%). CONCLUSION: Euroscore clearly
      overestimates the risk of surgery in this population of adults with congenital
      heart disease. Mortality and morbidity were low in those diagnosed bicuspid
      aortic valve, tetralogy of Fallot, or simple cardiac defect, justifying early
      surgery for incipient complications. Patients with complex congenital defect
      require prolonged ICU stay, sometimes with mechanical cardiac support, but their
      overall good outcome justifies these efforts.

PMID- 17177053
TI  - Is the diagnosis as simple as the treatment? Diagnostic pitfalls in chronic
      exertional compartment syndrome?

PMID- 17177054
TI  - Repetitive low-energy shock wave treatment is effective for chronic symptomatic
      plantar fasciitis.

PMID- 17177056
TI  - Albendazole therapy for eosinophilic meningitis caused by Angiostrongylus
      cantonensis.
AB  - Eosinophilic meningitis in humans is commonly caused by the nematode
      Angiostrongylus cantonensis. A severe headache is the most common presenting
      symptom. A prospective, randomized, double-blind, placebo, controlled study was
      conducted to determine if albendazole was efficacious in relieving such
      headaches. Seventy-one patients (36 and 35 in the treatment and control groups)
      were enrolled in the study. Five patients (two and three in the treatment and
      control groups) were excluded from the study because of being lost to follow-up,
      and the clinical data were incomplete. Therefore, 34 and 32 patients in the
      treatment and control groups were studied, respectively. Albendazole was
      administered at 15 mg/kg/day or identical placebo for 2 weeks. The number of
      patients with persistent headaches after 2 weeks was 7 and 13 in the albendazole
      and placebo groups (p = 0.08), respectively. The mean duration of a headache was
      8.9 and 16.2 days in the albendazole and placebo groups, respectively (p = 0.05).
      No serious drug events were observed. A 2-week course of albendazole appeared to
      reduce the duration of headache in eosinophilic meningitis.

PMID- 17177055
TI  - Evaluation of reward processes in an animal model of depression.
AB  - RATIONALE: Anhedonia is a core symptom of major depression. Deficits in reward
      function, which underlie anhedonia, can be readily assessed in animals.
      Therefore, anhedonia may serve as an endophenotype for understanding the neural
      circuitry and molecular pathways underlying depression. OBJECTIVE: Surprisingly,
      there is scant knowledge regarding alterations in brain reward function after
      olfactory bulbectomy (OB), an animal model which results in a behavioural
      syndrome responsive to chronic antidepressant treatment. Therefore, the present
      studies aimed to assess reward function after bulbectomy. MATERIALS AND METHODS:
      The present study utilized sucrose preference, cocaine-induced hyperlocomotion
      and intra-cranial self-stimulation (ICSS) responding to examine reward processes
      in the OB model. RESULTS: Bulbectomized animals showed a marked preference (>90%)
      for 0.8% sucrose solution compared with water; similar to the preference
      exhibited by sham controls. Importantly, there were pronounced deficits in brain
      reward function, as assessed using ICSS, which lasted 8 days before returning to
      baseline levels. Furthermore, bulbectomized animals were hyper-responsive to the
      locomotor stimulating properties of an acute and a repeated cocaine regimen.
      However, no difference in ICSS facilitation was observed in response to an acute
      cocaine injection. CONCLUSIONS: Taken together, these results suggest that
      bulbectomized rats display alterations in brain reward function, but these
      changes are not long-lasting and thus, not amenable to investigating the effects
      of pharmacological interventions. However, given that OB animals are
      hypersensitive to drugs of abuse, bulbectomy may be an appropriate inducing
      factor for the development of animal models of co-morbid depression and drug
      dependence.

PMID- 17177057
TI  - Cornea as a tissue reservoir of Trypanosoma cruzi.
AB  - Trypanosoma cruzi causal agent of Chagas' disease is a paninfective parasite of
      mammals transmitted through skin fecal contamination by Triatominae vectors.
      Studies of alternative routes for infection are scarce; therefore, eye infection
      should be important, because of the eye's high blood irrigation and brain
      proximity, as port of entry of the parasite. Trypanosoma cruzi parasites and/or
      their genetic material in ocular and adjacent muscle tissues were studied in
      batches of six NMRI mice (15 g) and Trichomys apereoides, an ancient caviomorph
      (250 g) inoculated with T. cruzi metacyclics from Brazilian (2) and Venezuelan
      (3) isolates genetically typified as T. cruzi I and II. Two animals/batch in the
      acute or chronic phase were killed and necropsies of cardiac and skeletal
      muscles, eyeball, and surrounding ocular muscle were processed for hematoxylin
      eosine staining. Tissue parasitism was determined. DNA of the digested sections
      of the eyeball (5-10 mum) was extracted for T. cruzi k-DNA amplification by PCR,
      with S35 and S36 primers. The PCR products were analyzed. The average of maximum
      values of parasitemia of all infected animals was of 10(5) trypomastigotes/ml
      blood. Skeletal muscle and heart were colonized in patent infection for all
      isolates. Amastigote nests were found in corneal tissue of 2/3 of the used
      isolates and adjacent ocular muscle and connective tissue were parasitized.
      Trypanosoma cruzi k-DNA (330-bp band) was observed in ocular tissue of 4/6 of the
      isolates studied in both animal models. Investigations concerning infection of
      the eye globe tissues by T. cruzi are extremely scarce. The presence of stages of
      T. cruzi and/or its genetic products in ocular tissues indicate a broad
      colonization from a systemic infection. The results show the ocular environment
      as a possible appropriate microniche for T. cruzi and emphasize the risk of
      transmitting T. cruzi by ocular fluids and by parasitized cornea through
      transplants.

PMID- 17177058
TI  - Trichobilharzia szidati: the lung phase of migration within avian and mammalian
      hosts.
AB  - The passage of Trichobilharzia szidati schistosomula through the vertebrate lungs
      was examined in natural and abnormal hosts--birds (ducks Anas platyrhynchos f.
      domestica) and mammals (mice Mus musculus Bagg albino/c [BALB/c]), respectively.
      Using the methods of classical histology, the migratory route of worms was
      characterized, and the impact of migration on host tissues and the host cell
      reactions were evaluated. Living schistosomula were recorded in the lungs of
      ducks 2-10 days post infection (p.i.) and in the lungs of mice 2-4 days p.i. In
      ducks, the schistosomula migrated from the blood vessels through the blood
      capillaries to the lung tissue; then, they entered free air space of the lungs.
      The infection resulted in inflammatory reaction with nodules composed of
      infiltrated lymphocytes, heterophils, eosinophils and macrophages. These
      structures were formed around the blood vessels and in the gas-exchange tissues
      of the parabronchial walls and, consequently, in the walls of secondary bronchi.
      An extensive inflammation of secondary bronchi and parabronchi was observed. In
      the lungs of mice, the parasites were localized extravascularly in the alveolar
      walls. No migratory pattern similar to that in the lungs of ducks was recorded.
      No specific inflammatory reaction occurred. However, alveolar wall congestion,
      edema and lymphocyte infiltrates appeared and, therefore, pathogenicity of T.
      szidati was also confirmed in the murine host.

PMID- 17177059
TI  - Seroprevalence of anti-Kudoa sp. (Myxosporea: Multivalvulida) antibodies in a
      Spanish population.
AB  - A majority of Kudoa species infect the somatic muscle of fish establishing cysts.
      Because there is no effective method to detect infected fish without destroying
      them, these parasitised fish reach the consumer. The elevated humoral responses
      detected previously by us in BALB/c mice immunised with Kudoa sp. pseudocyst
      extracts and the high IgG1 and IgE levels induced by the oral administration of
      Kudoa pseudocysts to BALB/c mice showed the possible immunopathological effects
      in man from the ingestion of Kudoa-infected fish. In this work, we investigated
      the seroprevalence of anti-Kudoa sp. antibodies in a Spanish healthy population
      and the possible association between the manifestation of allergic reactions
      after fish consumption and the humoral responses to Kudoa sp. antigens. Specific
      anti-Kudoa sp. antibody levels in sera of patients diagnosed with several
      digestive pathologies were also determined, studying their possible association
      with the alteration of analytic parameters in these patients.

PMID- 17177060
TI  - Maternal immunization by egg propagated gametocyte vaccine to control Eimeria
      tenella infections in newly hatched chicks.
AB  - The present paper reports the ability of egg-propagated gametocyte vaccine to
      induce protective immunity against Eimeria tenella infections in offspring
      chicks. For this purpose, breeding hens were immunized with adjuvanted gametocyte
      vaccine orally, being the best vaccine in our previous studies. Eggs collected 2
      weeks after the boosting dose were allowed to hatch. Upon challenge with
      sporulated oocysts of E. tenella (local isolates) to 7-day-old chicks from
      immunized hens showed more than 70% reduction in oocyst production compared with
      chicks from control hens. Furthermore, no mortality was recorded in immunized
      chickens, while four out of five control chickens died due to coccidiosis. These
      results suggested that maternal immunization with egg-propagated gametocyte
      vaccine can control E. tenella infections in offspring chicks.

PMID- 17177061
TI  - Strong linkage disequilibrium near the selected Yr17 resistance gene in a wheat
      experimental population.
AB  - Dynamic management (DM) is a method of genetic resources conservation that aims
      at maintaining evolutionary process in subdivided populations cultivated in
      contrasted environments. Such populations are often submitted to strong natural
      selection as it was the case for experimental wheat populations maintained under
      DM. Understanding impacts of selection on genetic diversity around selected genes
      is necessary for the middle-term maintenance of genetic variability in DM
      populations. Evolution of diversity at six neutral markers located near the
      yellow rust resistance gene Yr17 has been studied for the parental lines and for
      generations 1, 5, 10 and 17 in one of the DM populations. Yr17 provided complete
      resistance to yellow rust in France until 1997 and thus was suspected to be under
      strong selection. The gene is located on a fragment introgressed in winter wheat
      from a wild species. The presence of the gene was estimated using a marker
      closely related to the gene. We showed that the Yr17 gene has been selected
      between generations 5 and 10. Generally, selection tends to reduce diversity
      around selected genes, generating linkage disequilibrium (LD) between a gene and
      adjacent markers. Here, the major effect of the Yr17 gene selection was a
      reduction of multilocus diversity and the maintenance of strong pre-existing LD
      in the zone surrounding the gene for a distance of 20 cM. As expected, the
      presence of the exogenous introgression was responsible for restrictions to
      recombination which contributed to the maintenance of strong correlations between
      loci. However, we found a noticeable number of recombinations around the gene
      indicating a progressive incorporation of the fragment into the wheat genome.

PMID- 17177062
TI  - Genetic variations in rice in vitro cultures at the EPSPs-RPS20 region.
AB  - In vitro cultures of plant cells have often been utilized to generate genetic
      variations, which are designated somaclonal variations. Little is known about the
      major genetic alterations in the cultured cells and the nature of these genetic
      changes. Here, we examined different lines of rice Oc cells that have been
      cultured for more than 20 years on agar media or in liquid media. We surveyed 35
      clones obtained from PCR amplification of the 3-kb EPSPs-RPS20 region. The
      sequence divergence among the Oc cells was even greater than that between
      Japonica and Indica rice cultivars. The divergent sequences appeared to be
      maintained as multiple copies in a single cell. Surprisingly, the nucleotide
      substitutions in the Oc cells were characterized by an extremely high frequency
      of transition mutations of A/T-to-G/C, a feature which is similar to that of the
      mutations caused by chemical mutagens such as 5-bromouracil and 2-aminopurine.
      Although no replacements in the exons of this region were observed among the AA
      genome Oryza species, our results revealed that the nucleotide substitutions of
      the cultured cell lines occurred more frequently at replacement sites in the
      exons than at synonymous sites. These distinct mutation biases found in rice in
      vitro cultures might contribute importantly to somaclonal variations.

PMID- 17177063
TI  - Mapping resistance to Southern rust in a tropical by temperate maize recombinant
      inbred topcross population.
AB  - Southern rust, caused by Puccinia polysora Underw, is a foliar disease that can
      severely reduce grain yield in maize (Zea mays L.). Major resistance genes exist,
      but their effectiveness can be limited in areas where P. polysora is multi
      racial. General resistance could be achieved by combining quantitative and race
      specific resistances. This would be desirable if the resistance alleles
      maintained resistance across environments while not increasing plant maturity.
      Recombinant inbred (RI) lines were derived from a cross between NC300, a
      temperate-adapted all-tropical line, and B104, an Iowa Stiff Stalk Synthetic
      line. The RI lines were topcrossed to the tester FR615 x FR697. The 143
      topcrosses were scored for Southern rust in four environments. Time to flowering
      was measured in two environments. The RI lines were genotyped at 113 simple
      sequence repeat markers and quantitative trait loci (QTL) were mapped for both
      traits. The entry mean heritability estimate for Southern rust resistance was
      0.93. A multiple interval mapping model, including four QTL, accounted for 88% of
      the variation among average disease ratings. A major QTL located on the short arm
      of chromosome 10, explained 83% of the phenotypic variation, with the NC300
      allele carrying the resistance. Significant (P < 0.001), but relatively minor,
      topcross-by-environment interaction occurred for Southern rust, and resulted from
      the interaction of the major QTL with the environment. Maturity and Southern rust
      rating were slightly correlated, but QTL for the two traits did not co-localize.
      Resistance was simply inherited in this population and the major QTL is likely a
      dominant resistant gene that is independent of plant maturity.

PMID- 17177064
TI  - Development of allele-specific PCR and RT-PCR assays for clustered resistance
      genes using a potato late blight resistance transgene as a model.
AB  - Members of the NBS-LRR gene family impart resistance to a wide variety of
      pathogens and are often found clustered within a plant genome. This clustering of
      homologous sequences can complicate PCR-based characterizations, especially the
      study of transgenes. We have developed allele-specific PCR and RT-PCR assays for
      the potato late blight resistance gene RB. Our assay utilizes two approaches
      toward primer design, allowing discrimination between the RB transgene and both
      the endogenous RB gene and numerous RB homeologs. First, a reverse primer was
      designed to take advantage of an indel present in the RB transgene but absent in
      rb susceptibility alleles, enhancing specificity for the transgene, though not
      fully discriminating against RB homeologs. Second, a forward primer was designed
      according to the principles of mismatch amplification mutation assay (MAMA) PCR,
      targeting SNPs introduced during the cloning of RB. Together, the indel reverse
      primer and the MAMA forward primer provide an assay that is highly specific for
      the RB transgene, being capable of distinguishing the transgene from all RB
      endogenous gene copies and from all RB paralogs in a diverse collection of wild
      and cultivated potato genotypes. These primers have been successfully multiplexed
      with primers of an internal control. The multiplexed assay is useful for both PCR
      and RT-PCR applications. Double MAMA-PCR, in which both PCR primers target
      separate transgene-specific SNPs, was also tested and shown to be equally
      specific for the RB transgene. We propose extending the use of MAMA for the
      characterization of resistance transgenes.

PMID- 17177066
TI  - Long-term colchicine therapy in a patient with Behcet's disease and acute
      promyelocytic leukemia.
AB  - Behcet's disease causes a continuous T-lymphocytic mediated inflammatory reaction
      in the small arterioles, which results in gradual destruction of any human organ
      or system. The benefit of treatment with colchicine in patients with Behcet's
      disease has been reported in literature. Acute leukemia has seldom been
      associated with Behcet's disease, although acute promyelocytic leukemia is a
      particular subtype of leukemia that is often characterized by special cytogenetic
      abnormalities. We report a male patient with acute promyelocytic leukemia and
      Behcet's disease who had received long-term treatment with colchicine. To our
      knowledge, this is the first report of the concomitant occurrence of acute
      promyelocytic leukemia and Behcet's disease, which suggests that long-term
      colchicine therapy has a role in the pathogenesis of acute promyelocytic
      leukemia. The patient described has been treated with retinoic acid and
      idarubicin (the ATRA-IDA protocol). At the time of this writing, his disease is
      in clinical remission.

PMID- 17177065
TI  - Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and
      potential therapies.
AB  - INTRODUCTION: Restoration of blood flow following ischemic stroke can be achieved
      by means of thrombolysis or mechanical recanalization. However, for some
      patients, reperfusion may exacerbate the injury initially caused by ischemia,
      producing a so-called "cerebral reperfusion injury". Multiple pathological
      processes are involved in this injury, including leukocyte infiltration, platelet
      and complement activation, postischemic hyperperfusion, and breakdown of the
      blood-brain barrier. METHODS/RESULTS AND CONCLUSIONS: Magnetic resonance imaging
      (MRI) can provide extensive information on this process of injury, and may have a
      role in the future in stratifying patients' risk for reperfusion injury following
      recanalization. Moreover, different MRI modalities can be used to investigate the
      various mechanisms of reperfusion injury. Antileukocyte antibodies, brain cooling
      and conditioned blood reperfusion are potential therapeutic strategies for
      lessening or eliminating reperfusion injury, and interventionalists may play a
      role in the future in using some of these therapies in combination with
      thrombolysis or embolectomy. The present review summarizes the mechanisms of
      reperfusion injury and focuses on the way each of those mechanisms can be
      evaluated by different MRI modalities. The potential therapeutic strategies are
      also discussed.

PMID- 17177067
TI  - Long-term effects of 7-monohydroxyethylrutoside (monoHER) on DOX-induced
      cardiotoxicity in mice.
AB  - Doxorubicin (DOX) is a potent antitumor agent for different types of cancer, but
      the cumulative, dose-related cardiotoxicity limits its clinical use. The
      incidence of abnormal cardiac function after treatment with DOX appears to
      increase with time. Therefore, late cardiotoxicity is-especially in young
      surviving patients-a major concern. The aim of this study was to evaluate in mice
      whether the semisynthetic flavonoid 7-monohydroxyethylrutoside (monoHER) also
      protected against DOX-induced cardiotoxicity after a long period of follow-up.
      Four groups of 6 Balb/c mice were treated weekly during 6 weeks with saline, DOX
      alone (4 mg/kg i.v.), DOX preceded by monoHER (500 mg/kg i.p.), or DOX preceded
      by monoHER followed by long-term weekly monoHER injections during the observation
      period of 6 months. Half of the mice treated with DOX only developed DOX-induced
      heart failure and died within 6 months of observation. Two mice co-treated with
      monoHER showed weight loss and shortness of breath, whereas one mouse was found
      dead in its cage known with weight loss. The group receiving DOX plus long-term
      repeated doses of monoHER started to lose weight. Five out of six mice in this
      group developed shortness of breath and died before the end of the study with
      symptoms of cardiac failure induced by DOX. Statistical comparison of the
      histological heart damage between the different experimental groups was not
      possible, because the animals died at different time-points in the observation
      period and DOX-induced cardiotoxicity progressed with time. Nevertheless, it was
      clear that the initial cardioprotective effect of monoHER was not prolonged
      during the half-year observation period. It was even suggested that addition of
      repeated doses of monoHER tended to aggravate DOX-induced cardiotoxicity. It
      cannot be excluded that the dose and frequency of monoHER administration is
      crucial in obtaining an optimal antioxidant activity without a pro-oxidant
      activity of monoHER.

PMID- 17177068
TI  - Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the role
      of matched platelet transfusion and IVIG.
AB  - We evaluated the effects of platelet transfusions and intravenous immunoglobulin
      (IVIG) in neonates with fetal and neonatal alloimmune thrombocytopenia (FNAIT)
      with and without antenatal treatment with IVIG. Records of neonates with FNAIT
      admitted between January 2000 and November 2005 were reviewed. The patients were
      divided into group I, treated antenatally with IVIG for known FNAIT, and group
      II, postnatally diagnosed with FNAIT. The primary outcome was the time interval
      to reach a platelet level above 100 x 10(9)/L in relation to the type of
      treatment. Nineteen neonates with FNAIT were identified, 13 in group I and 6 in
      group II. In group I, four children were born with a platelet count above 100 x
      10(9)/L and never needed treatment, and four received a single matched platelet
      transfusion at birth with a maintained response. Five neonates received IVIG and
      one matched transfusion, with all but one rapidly responding. In antenatally
      treated cases, postnatal IVIG had no apparent effect on the platelet count. In
      group II, two neonates died on day 1 with severe intracranial hemorrhage. Two of
      the four other patients responded to a number of unmatched platelet transfusions,
      with one neonate rapidly responding after one matched transfusion, while another
      needed nine matched transfusions before a persistent adequate platelet count was
      reached after 9 weeks. Postnatal IVIG had no apparent effect on the platelet
      count in any of our cases. In neonates with FNAIT treated antenatally with IVIG,
      neonatal management using a single matched platelet transfusion was adequate in
      all cases. In neonatally diagnosed cases not treated before birth, multiple
      matched platelet transfusions may be required. We found no evidence to support
      the use of IVIG in neonates with FNAIT.

PMID- 17177069
TI  - Detection of respiratory pathogens by real-time PCR in children with clinical
      suspicion of pertussis.
AB  - The use of a multiplex respiratory real-time PCR in patients clinically suspected
      of pertussis increases the number of pathogens detected.

PMID- 17177070
TI  - From hyperinsulinaemic hypoglycaemia to ketotic hypoglycaemia: the range of
      glucose abnormalities in patients born with intrauterine growth retardation.
AB  - INTRODUCTION: Newborns with intrauterine growth retardation (IUGR) have multiple
      risk factors for developing hypoglycaemia. Hyperinsulinism, both transient and
      prolonged, is one of the major risk factors responsible for the hypoglycaemia
      observed in some newborns with IUGR. Once the child has progressed beyond the
      infancy period, the most common cause of hypoglycaemia is ketotic hypoglycaemia.
      We report our observations of ketotic hypoglycaemia in six children who were born
      with IUGR and developed hyperinsulinaemic hypoglycaemia (HH) that required
      treatment with diazoxide and chlorothiazide. RESULTS: In one of these children
      the ketotic hypoglycaemia was found to be due to growth hormone deficiency; in
      the remaining five patients, however, no cause for the hypoglycaemia could be
      found, despite extensive investigations. These observations suggest that ketotic
      hypoglycaemia may be more common in children with a history of IUGR. Further
      studies are required to understand why some newborns with IUGR and HH have an
      increased risk of ketotic hypoglycaemia in childhood. CONCLUSION: Newborns with a
      history of IUGR and HH have an increased risk of developing ketotic hypoglycaemia
      in the childhood period.

PMID- 17177071
TI  - Hamamelis in children with skin disorders and skin injuries: results of an
      observational study.
AB  - Published clinical experience with hamamelis ointment in children is limited.
      This observational study included children (age 27 days to 11 years) with minor
      skin injuries, diaper dermatitis, or localized inflammation of skin. The children
      received either hamamelis ointment or dexpanthenol ointment in groups at a 3-to-1
      ratio. Baseline and post-treatment assessments compared the total scores of
      predefined signs and symptoms for each condition. Physicians and parents were
      asked for a global assessment of efficacy and tolerability of the respective
      treatments at the end of therapy. A total of 309 children were treated (hamamelis
      n = 231; dexpanthenol n = 78). The treatment groups were comparable regarding
      demographic data and baseline total scores of signs and symptoms. In all three
      diagnosis groups, the efficacy of hamamelis and dexpanthenol was shown by a
      statistically significant and clinically relevant decrease of total scores from
      baseline to endpoint (p < 0.0001 for each group, Wilcoxon signed-rank test).
      Overall, the results for the hamamelis and the dexpanthenol groups were similar.
      Descriptive advantages for the hamamelis group were observed for a number of
      parameters and diagnosis groups. Both treatments were well tolerated. Ratings of
      the tolerability of hamamelis were "excellent" or "good" in 99.1% (physicians)
      and 98.2% (parents) of cases, respectively. The corresponding ratings for
      dexpanthenol were 97.4 and 92.3%. In conclusion, hamamelis ointment is an
      effective and safe treatment for certain skin disorders in children up to the age
      of 11 years. The observed effects are similar to dexpanthenol.

PMID- 17177073
TI  - Linker region of nebulin family members plays an important role in targeting
      these molecules to cellular structures.
AB  - The nebulin family of actin-binding proteins plays an essential role in
      cytoskeletal dynamics and actin filament stability. All of the family members are
      modular proteins with their key defining structural feature being the presence of
      the 35-residue nebulin modules. The family members now include nebulin,
      nebulette, N-RAP, LASP-1, and LIM-nebulette. Nebulin and nebulette are associated
      with the thin filament/Z-line junction of striated muscle. LASP-1 and LIM
      nebulette are found within focal adhesions, and N-RAP is associated with muscle
      cellular junctions. Although much investigation has focused on the role of the
      interactions between nebulin modules and actin, each of these proteins contains
      other domains that are essential for their cellular targeting and functions. The
      serine-rich linker region of nebulette has previously been shown to serve just
      such a purpose by targeting the association of the nebulin modules to the cardiac
      Z-line in cultured cardiomyocytes. In this report, we analyze the targeting
      functions of the homologous regions of LASP-1 and LIM-nebulette in their
      incorporation into focal adhesions. We have found that the linker region of LASP
      1 is indeed important for its cellular localization and that the shortened linker
      region of LIM-nebulette drives the association of nebulin modules to focal
      adhesions.

PMID- 17177074
TI  - Structural properties of proteins specific to the myelin sheath.
AB  - The myelin sheath is an insulating membrane layer surrounding myelinated axons in
      vertebrates, which is formed when the plasma membrane of an oligodendrocyte or a
      Schwann cell wraps itself around the axon. A large fraction of the total protein
      in this membrane layer is comprised of only a small number of individual
      proteins, which have certain intriguing structural properties. The myelin
      proteins are implicated in a number of neurological diseases, including, for
      example, autoimmune diseases and peripheral neuropathies. In this review, the
      structural properties of a number of myelin-specific proteins are described.

PMID- 17177076
TI  - Rotigotine transdermal system for perioperative administration.
AB  - We present a series of patients participating in clinical trials with the
      rotigotine transdermal system. All patients were scheduled for surgery with
      general anaesthesia unrelated to the trial procedure or to rotigotine.
      Perioperative administration of rotigotine appeared to be feasible and
      efficacious. No safety issues emerged from these observations.

PMID- 17177075
TI  - Rasagiline is neuroprotective in an experimental model of brain ischemia in the
      rat.
AB  - The neuroprotective effects of intravenous rasagiline were investigated in a rat
      model of stroke. Middle cerebral artery (MCA) occlusion was performed in male
      rats and the short- (neurological severity score [NSS], infarct size),
      intermediate- (cognition) and long-term (necrotic area) effects were assessed. A
      bolus (3 mg/kg) of rasagiline followed by a 3-h infusion (3 mg/kg/h), initiated
      immediately after MCA occlusion, reduced infarct size by 48.6% and NSS by 32.7%
      relative to saline treatment. Cognitive function, tested in a water maze 2-3
      weeks after occlusion, also significantly improved compared with saline-treated
      controls. Necrotic brain area was 35-50% smaller with rasagiline than with saline
      following a single bolus dose. The single bolus rasagiline dose was as effective
      as a rasagiline bolus followed by rasagiline infusion in short-term outcomes. The
      neuroprotective effect of rasagiline was fully reproducible when administered at
      2 h following occlusion but not after 4 h.

PMID- 17177078
TI  - Diaphragm pacing with natural orifice transluminal endoscopic surgery: potential
      for difficult-to-wean intensive care unit patients.
AB  - BACKGROUND: Up to 50% of the patients in the intensive care unit (ICU) require
      mechanical ventilation, with 20% requiring the use of a ventilator for more than
      7 days. More than 40% of this time is spent weaning the patient from mechanical
      ventilation. Failure to wean from mechanical ventilation can in part be
      attributable to rapid onset of diaphragm atrophy, barotrauma, posterior lobe
      atelectasis, and impaired hemodynamics, which are normally improved by
      maintaining a more natural negative chest pressure. The authors have previously
      shown that laparoscopic implantation of a diaphragm pacing system benefits
      selected patients. They now propose that an acute ventilator assist with
      interventional neurostimulation of the diaphragm in the ICU is feasible and could
      facilitate the weaning of ICU patients from mechanical ventilation. Natural
      orifice transluminal endoscopic surgery (NOTES) has the potential to expand the
      benefits of the diaphragm pacing system to this acute patient population by
      allowing it to be performed at the bedside similarly to insertion of the common
      gastrostomy tube. This study evaluates the feasibility of this approach in a
      porcine model. METHODS: Pigs were anesthetized, and peritoneal access with the
      flexible endoscope was obtained using a guidewire, needle knife cautery, and
      balloon dilation. The diaphragm was mapped using a novel endoscopic
      electrostimulation catheter to locate the motor point (where stimulation provides
      complete contraction of the diaphragm). An intramuscular electrode then was
      placed at the motor point with a percutaneous needle. The gastrotomy was managed
      with a gastrostomy tube. RESULTS: Four pigs were studied, and the endoscopic
      mapping instrument was able to map the diaphragm to identify the motor point. In
      one animal, a percutaneous electrode was placed into the motor point under
      transgastric endoscopic visualization, and the diaphragm could be paced in
      conjunction with mechanical ventilation. CONCLUSIONS: These animal studies
      demonstrate the feasibility of transgastric mapping of the diaphragm and
      implantation of a percutaneous electrode for therapeutic diaphragmatic
      stimulation.

PMID- 17177077
TI  - Severely disordered esophageal peristalsis is not a contraindication to
      laparoscopic Nissen fundoplication.
AB  - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the preferred operation
      for the control of gastroesophageal reflux disease (GERD). The use of a full
      fundoplication for patients with esophageal dysmotility is controversial.
      Although LNF is known to be superior to a partial wrap for patients with weak
      peristalsis, its efficacy for patients with severe dysmotility is unknown. We
      hypothesized that LNF is also acceptable for patients with severe esophageal
      dysmotility. METHODS: A multicenter retrospective review of consecutive patients
      with severe esophageal dysmotility who underwent an LNF was performed. Severe
      dysmotility was defined by manometry showing an esophageal amplitude of 30 mmHg
      or less and/or 70% or more nonperistaltic esophageal body contractions. RESULTS:
      In this study, 48 patients with severe esophageal dysmotility underwent LNF. All
      the patients presented with symptoms of GERD, and 19 (39%) had preoperative
      dysphagia. A total of 10 patients had impaired esophageal body contractions,
      whereas 32 patients had an abnormal esophageal amplitude, and 6 patients had
      both. The average abnormal esophageal amplitude was 24.9 +/- 5.2 mmHg (range, 6.0
      30 mmHg). The mean percentage of nonperistaltic esophageal body contractions was
      79.4% +/- 8.3% (range, 70-100%). There were no intraoperative complications and
      no conversions. Postoperatively, early dysphagia occurred in 35 patients (73%).
      Five patients were treated with esophageal dilation, which was successful in
      three cases. One patient required a reoperative fundoplication. Overall,
      persistent dysphagia was found in two patients (4.2%), including one patient with
      severe preoperative dysphagia, which improved postoperatively. Abnormal
      peristalsis and/or distal amplitude improved postoperatively in 12 (80%) of
      retested patients. There were no cases of Barrett's progression to dysplasia or
      carcinoma. During an average follow-up period of 25.4 months (range, 1-46
      months), eight patients (16%) were receiving antireflux medications, with six of
      these showing normal esophageal pH study results. CONCLUSION: The LNF procedure
      provides low rates of reflux recurrence with little long-term postoperative
      dysphagia experienced by patients with severely disordered esophageal
      peristalsis. Effective fundoplication improved esophageal motility for most of
      the patients. A 360 degrees fundoplication should not be contraindicated for
      patients with severe esophageal dysmotility.

PMID- 17177079
TI  - Use of fibrin glue (Tissucol) in laparoscopic repair of abdominal wall defects:
      preliminary experience.
AB  - INTRODUCTION: The aim of this study was to establish the efficacy and
      tolerability of human fibrin glue (Tissucol) for the nontraumatic fixation of a
      composite prosthesis (Parietex) in the laparoscopic repair of small to medium
      sized incisional hernias and primary defects of the abdominal wall. MATERIALS AND
      METHODS: From October 2003 to October 2005, 40 patients underwent laparoscopic
      repair at the hands of one surgeon with expertise in laparoscopic surgery; all
      meshes were implanted in an intraperitoneal position. Follow-up visits were
      scheduled for 7 days and 1, 6, and 12 months. These included assessments for pain
      and postoperative complications. RESULTS: Forty patients (24 females, 16 males)
      with a mean age of 50 years (range, 26-65 years) and a mean Body Mass Index (BMI)
      of 27 (range 25 to 30) were included in the study. Sixteen patients had
      incisional hernias, and 24 had primary defects. The size of the defects varied
      from 2 to 7 cm. Adhesiolysis was necessary in 92.5% of cases (25/40). There were
      no intraoperative complications or conversions. After a mean follow-up of 16
      months (range, 3-24 months), no postoperative complications were observed. The
      mean surgical intervention time was 36 min (range, 12-40 min), with an average
      hospitalization time of 1 day. CONCLUSIONS: The use of fibrin glue in the present
      study provided stable and uniform fixation of the prosthesis and minimized
      intraoperative and postoperative complications. Consequently, laparoscopic
      treatment of small to medium-sized abdominal defects using this approach is our
      therapeutic option of choice.

PMID- 17177080
TI  - A vertical scanning Doppler probe identifies blood vessels during laparoscopic
      surgery.
AB  - BACKGROUND: Using a conventional Doppler probe, it is difficult to identify blood
      vessels precisely in lymph node dissection during laparoscopic surgery. METHODS:
      For 26 patients undergoing laparoscopic colectomy and 26 patients undergoing
      laparoscopic subtotal gastrectomy, we used conventional and vertical scanning
      Doppler probes to compare their ability to identify invisible blood vessels
      through differences in power output voltage. RESULTS: The vertical scanning
      Doppler probe was 100% successful in identifying the target blood vessels
      regardless of the patient's body mass index (BMI), and also was superior to the
      conventional Doppler probe in detection sensitivity. The vertical scanning
      Doppler probe was useful for image training of recently qualified surgeons
      through real-time monitoring of the probe position and response on the monitor.
      Furthermore, findings showed that the vertical scanning Doppler probe was
      applicable to lymph node dissection as a forceps for laparoscopic usage.
      CONCLUSION: The vertical scanning Doppler could identify the target blood vessels
      regardless of the patient's BMI. It was verified to be useful as a surgical
      assistive device apart from being a sensor and may serve in the education of
      recently qualified surgeons.

PMID- 17177081
TI  - Assessment of pancreatic malignancy with laparoscopy and intraoperative
      ultrasound.
AB  - BACKGROUND: Staging laparoscopy for pancreatic malignancy is controversial. This
      study aimed to assess the efficacy of laparoscopy with intraoperative ultrasound
      in the management of patients with pancreatic carcinoma. METHODS: The study
      involved patients undergoing laparoscopy and intraoperative ultrasound over a
      period of 42 months. The entry criteria specified radiologic (computed
      tomography) diagnosis of pancreatic carcinoma and no evidence of metastases.
      RESULTS: The study enrolled 100 patients (52 men and 48 women) ages 21 to 83
      years (mean, 63 years). On the basis of imaging, 75 patients had lesions judged
      to be operable, and 25 patients had a pancreatic head lesion larger than 4 cm
      radiologically, considered to be unresectable, but with no evidence of metastatic
      disease. At laparoscopy, three patients had a normal examination, with no
      evidence of a pancreatic mass, and an additional seven patients had other
      pathology including one lymphoma, one ampullary tumor, two cases of chronic
      pancreatitis, and three sarcomas. Of the patients with radiologically inoperable
      disease, 16% had previously undetected metastases, but 24% were judged to be
      suitable for curative resection. Half of these patients underwent successful
      resection. Of the patients with radiologically operable disease, undetected liver
      or peritoneal metastases were found in 20% of the body or tail lesions and in 26%
      of the pancreatic head lesions. Of the pancreatic head tumors, 12% were found to
      be larger than 4 cm and therefore unsuitable for curative resection.
      Consequently, only 53% were confirmed to be suitable for resection. Of the
      patients explored with a view to curative resection, 42% actually underwent
      resection, with clearance of resection margins achieved in 77.8%. CONCLUSION: Of
      the patients thought to have a resectable tumor on the basis of good quality
      preoperative imaging, 44% had their management approach altered after laparoscopy
      and avoided an open procedure. Laparoscopy should therefore be used in the
      preoperative staging of pancreatic tumors.

PMID- 17177082
TI  - Abdominal lymphangiomas in children: interest of the laparoscopic approach.
AB  - BACKGROUND: Lymphangiomas are rare benign lesions of the lymphatic system. The
      most common symptoms are abdominal tumor or "acute abdomen" in children. The
      treatment of choice is complete surgical resection, but the recurrence rate with
      incomplete resection is high, and laparotomy exposes the patient to adhesions.
      The authors report their experience with the lymphangioma laparoscopic approach.
      METHODS: This retrospective study examined 15 consecutive operations for
      lymphangiomas in children, ages 5 months to 14 years, treated during the 5-year
      period from 1999 to 2004. RESULTS: Six patients were treated using the primary
      laparotomy approach, and nine patients underwent the laparoscopic procedure, six
      successfully. Three conversions were necessary (1 case requiring partial
      colectomy, 1 retroperitoneal case with adherence on the aorta and vena cava, 1
      case with partial volvulus). Morbidity included two cases of acute occlusion
      caused by adhesions after laparotomy. There was no recurrence of lymphangioma
      during a mean follow-up period of 35 months. CONCLUSION: The laparoscopy
      procedure could be used successfully for abdominal lymphangioma, even in an
      emergency. When the laparoscopic resection is impossible, laparotomy or
      sclerotherapy can be discussed.

PMID- 17177083
TI  - Laparoscopic excision of duodenal schwannoma.
AB  - BACKGROUND: Benign duodenal tumours are rare and less common than malignant
      tumours. They comprise a wide variety of pathologies. Schwannoma is an ectodermal
      neoplasm arising from the nerve sheath that envelops axons. A duodenal location
      is extremely rare. Therapy consists in the radical excision of the tumour. Our
      aim was to describe a minimally invasive technique used for the excision of
      duodenal schwannoma, so that a laparotomy has been avoided. METHODS: A
      laparoscopic operation under general anaesthesia was undertaken with the patient
      in supine position with the legs abducted. No macroscopic peritoneal seedling was
      found. Therefore, a laparoscopic Kocher maneuver was performed. The
      retroperitoneum was entered using the harmonic scalpel and the dissection
      extended beyond the vena cava and the duodenum. The location and the size of the
      lesion have been confirmed using an intraoperative endoscopic ultrasound
      examination. The excision of the lesion was performed by use the harmonic
      scalpel. Then, the duodenal wall was sutured by use endoscopic stitches. The
      resected lesion was then placed in a retrieval bag and extracted through the port
      incision. Operating time was 300 min and blood loss 200 ml. RESULTS: The
      postoperative course was uneventful. Histological findings showed a benign
      schwannoma. CONCLUSIONS: The minimally invasive technique may be a valid
      alternative to open surgery in the treatment of benign duodenal tumors.

PMID- 17177084
TI  - Self-expanding Polyflex plastic stents in esophageal disease: various
      indications, complications, and outcomes.
AB  - BACKGROUND: Esophageal stenting has become an important technique in the
      treatment of different clinical problems such as malignant or benign stenosis,
      anastomotic leaks after surgery, or fistulas. In this study we present our
      experience with the self-expanding Polyflex plastic stent in various indications,
      arising complications, and patient's outcomes. METHODS: Over a three-year period,
      35 patients underwent self-expanding Polyflex plastic stent placement for
      esophageal stenosis (n = 23) with 22 malignant, and for perforations, fistulas,
      or anastomotic leaks after surgery (n = 12). The short-term efficacy and long
      term outcomes were analyzed. RESULTS: In patients with stenosis, implantation was
      performed without any complications in 91% (21/23). In one patient perforation
      occurred while passing the stenosis; in another patient the stent dislocated
      during the insertion procedure. Dysphagia score improved from 3.0 to 1.0 after
      stenting. In all patients with perforations, fistulas, or anastomotic leaks (n =
      12), stents were placed successfully without any complication. Complete sealing
      of the mucosal defect was proven by radiography in 92% (n = 11) and healing was
      seen in 42% (n = 5). If indicated, stent removal was performed without any
      complications. Stent migration (n = 13; 37%) was the most common long-term
      complication. CONCLUSIONS: The placement of self-expanding Polyflex plastic
      stents is a highly sufficient and cost-effective treatment for malignant and
      benign esophageal disorders. Because the long-term results were highly favorable,
      self-expanding plastic stent placement could be used as the initial treatment for
      various conditions.

PMID- 17177085
TI  - Teaching robotic surgery: a stepwise approach.
AB  - BACKGROUND: After an initial institutional experience with 50 robot-assisted
      laparoscopic Roux-en-Y gastric bypass procedures, a curriculum was developed for
      fellowship training in robotic surgery. METHODS: Thirty consecutive robotic
      gastric bypasses were performed using the Zeus robotic surgical system to fashion
      a two-layer gastrojejunostomy. For teaching purposes, performance of the
      anastomosis was divided into three discrete tasks. Robotic suturing tasks were
      assigned to the trainee in cumulative order in ten-case increments. Our patient
      population averaged 44 years of age and 47 kg/m(2) in BMI. Patients were
      predominantly female (87%). RESULTS: The robotic training experience of the
      fellow defines the increases in surgical responsibility over the series of cases.
      Statistical analysis revealed no significant differences in task times or total
      robotic operative time as participation of the trainee in performing the
      gastrojejunostomy increased. No adverse robotic events or surgical complications
      occurred throughout this series. The learning curve of the fellow compared
      favorably with the initial experience of the institution. CONCLUSION: Robotic
      surgery training may be safely implemented in a minimally invasive surgery
      training program. A gradual introduction of robotic technique appears to maximize
      the learning experience and minimize the potential for adverse outcomes.

PMID- 17177086
TI  - Transoral diverticulostomy with a modified Endo-Gia stapler: results after 4
      years of experience.
AB  - BACKGROUND: The incidence of Zenker's diverticulum is low (2/100,000). Standard
      surgical treatment is cricopharyngeal myotomy with diverticulectomy. Various
      minimally invasive surgical approaches pursued recently have treated Zenker's
      diverticulum adequately. The functional minimally invasive therapy is performed
      alternatively using an Endo-Gia stapler inserted transorally to perform an
      esophageal diverticulostomia, or using thermal coagulation applied by a carbon
      dioxide (CO2) or argon plasma laser. The key to a successful procedure is
      adequate exposure of the diverticulum by insertion of a pharynx spreader before
      the surgery. METHODS: Since 1996, 31 patients who underwent minimally invasive
      diverticulostomies performed in our clinic have been included prospectively in
      the current study. All the patients were examined endoscopically before and after
      surgery. Furthermore, the intraesophageal and intragastric pressure was examined
      by transesophageal manometry, and the pH in the esophagus and stomach was
      determined by pH-metry. A barium swallow was performed to exclude leakage at the
      stapler suture line as proof of sufficient anastomoses. Manometry showed that the
      upper esophageal sphincter functioned normally before and after surgery. The
      results were compared with those of patients undergoing conventional procedures.
      RESULTS: The median follow-up period after resection of the diverticulum was 46
      months. Both the Gastrointestinal Quality-of-Life Index (GQLI) (p < 0.001) and
      the modified dysphagia score (GHDS) increased significantly, indicating that the
      operations were successful. The minimally invasive procedure is faster than
      cricopharyngeal myotomy and significantly safer. It is better tolerated by
      patients, and they are discharged earlier. CONCLUSION: Transoral
      esophagodiverticulosomy has become the standard procedure for Zenker's
      diverticulum in the authors' department. The endoscopic minimally invasive
      approach proved to be safer than standard surgical procedures. It offers a
      significantly shorter operation time and postoperative hospital stay (p < 0.001).

PMID- 17177087
TI  - Trocar site hernia after laparoscopic ventral hernia repair.
AB  - BACKGROUND: The incidence of trocar site hernia (TSH) after laparoscopic ventral
      hernia repair (LVHR) is reported to be low. The present study investigates the
      associated risk factors, with a view to preventing this complication. METHODS: A
      retrospective study was made of the incidence of TSH in a personal series of
      LVHR, recording anthropometric and clinical data on the patients. Risk factors
      were assessed by bivariate and multivariate analyses. The patients were subjected
      to clinical and telephone follow-up. RESULTS: In a series of 27 LVHR, the
      incidence of TSH was 22% (6 patients). The use of meshes larger than 10 x 15 cm
      for LVHR was the only TSH risk factor to reach statistical significance. Female
      gender and diabetes showed a higher incidence in the TSH group. CONCLUSIONS: The
      use of large meshes may be a risk factor for TSH. We believe this to be due to
      dilatation of the trocar orifice during introduction of the mesh, and also to
      postoperative retraction of the mesh.

PMID- 17177088
TI  - Haplotype diversity in "source-sink" dynamics of Escherichia coli urovirulence.
AB  - FimH, the mannose-specific, type 1 fimbrial adhesin of Escherichia coli, acquires
      amino acid replacements adaptive in extraintestinal niches (the genitourinary
      tract) but detrimental in the main habitat (the large intestine). This
      microevolutionary dynamics is reminiscent of an ecological "source-sink" model of
      continuous species spread from a stable primary habitat (source) into transient
      secondary niches (sink), with eventual extinction of the sink-evolved
      populations. Here, we have adapted two ecological analytical tools-diversity
      indexes DS and alpha--to compare size and frequency distributions of fimH
      haplotypes between evolutionarily conserved FimH variants ("source" haplotypes)
      and FimH variants with adaptive mutations (putative "sink" haplotypes). Both
      indexes show two- to threefold increased diversity of the sink fimH haplotypes
      relative to the source haplotypes, a pattern that ran opposite to those seen with
      nonstructural fimbrial genes (fimC and fimI) and housekeeping loci (adk and fumC)
      but similar to that seen with another fimbrial adhesin of E. coli, papG-II, also
      implicated in extraintestinal infections. The increased diversity of the sink
      pool of adhesin genes is due to the increased richness of the haplotypes (the
      number of unique haplotypes), rather than their evenness (the extent of
      similarity in relative abundances). Taken together, this pattern supports a
      continuous emergence and extinction of the gene alleles adaptive to virulence
      sink habitats of E. coli, rather than a one-time change in the habitat
      conditions. Thus, ecological methods of species diversity analysis can be
      successfully adapted to characterize the emergence of microbial virulence in
      bacterial pathogens subject to source-sink dynamics.

PMID- 17177089
TI  - A new retroposed gene in Drosophila heterochromatin detected by microarray-based
      comparative genomic hybridization.
AB  - A genomic pattern of new gene origination is often dependent on a genomic method
      that can efficiently identify a statistically adequate number of recently
      originated genes. The heterochromatic regions have often been viewed as genomic
      deserts with low coding potential and thus a low flux of new genes. However,
      increasing reports revealed unexpected roles of heterochromatic regions in the
      evolution of genes and genomes. We identified recently retroposed genes that
      originated in heterochromatic regions in Drosophila, by developing microarray
      based comparative genomic hybridization (CGH) with multiple species. This new
      gene family, named Ifc-2h, originated in the common ancestor of the clade of D.
      simulans, D. mauritiana, and D. sechellia. The sequence features and phylogenetic
      distribution indicated that Ifc-2h resulted from the retroposition from its
      parental gene, Infertile crescent (Ifc), and integrated into heterochromatic
      region of common ancestor of the three sibling species 2 million years ago.
      Expression analysis revealed that Ifc-2h had developed a new expression pattern
      by recruiting a putative regulatory element from its target sequence. The
      distribution of indel variation in Ifc-2h of D. simulans and D. mauritiana
      revealed a significant sequence constraint, suggesting that the Ifc-2h gene may
      be functional. These analyses cast fresh insight into the evolution of
      heterochromatin and the origin of its coding regions.

PMID- 17177091
TI  - [116-119th session of the Provisional Synthetic Material Commission of the BFR:
      Report from 10-11 November 2004, 13-14 April 2005, 23-24 November 2005 and 5
      April 2006].

PMID- 17177092
TI  - [Effects of fine particular matter pollution on mortality and life expectancy].

PMID- 17177093
TI  - [A separation of public health ethics from medical ethics].
AB  - Until now there are only a few approaches in the German-speaking realm to
      establish an explicit ethical framework for moral issues of public health-
      although a need for public health ethics in times of SARS and avian flu is
      obvious. One deficit of the discussion so far is that there is no systematic
      separation of medical ethics and public health ethics. Thus, the core and
      interdisciplinary focus of public health is often not met. However, to frame
      discussions of moral issues within a specific public health ethics framework
      seems to be fruitful. This paper deals with the conceptual differences of medical
      ethics and public health ethics. The discussion helps both applied ethical
      discourses to sharpen their focus and strengthen their appeal. The author
      develops and presents a conceptual and normative frame for public health ethics
      and offers a concise set of ethical principles for the discussion of moral
      challenges in public health.

PMID- 17177090
TI  - Loss of introns along the evolutionary diversification pathway of snake venom
      disintegrins evidenced by sequence analysis of genomic DNA from Macrovipera
      lebetina transmediterranea and Echis ocellatus.
AB  - Analysis of cDNAs from Macrovipera lebetina transmediterranea (Mlt) and Echis
      ocellatus (Eo) venom gland libraries encoding disintegrins argued strongly for a
      common ancestry of the messengers of short disintegrins and those for precursors
      of dimeric disintegrin chains. We now report the sequence analysis of disintegrin
      coding genes from these two vipers. Genomic DNAs for dimeric disintegrin subunits
      Ml_G1 and Ml_G2 (Mlt) and Eo_D3 (Eo) contain single 1-kb introns exhibiting the
      5'-GTAAG (donor)/3'-AG (acceptor) consensus intron splicing signature. On the
      other hand, the short RTS-disintegrins Ml_G3 (Mlt) and Eo_RTS (Eo) and the short
      RGD-disintegrin ocellatusin (Eo) are transcribed from intronless genomic DNA
      sequences, indicating that the evolutionary pathway leading to the emergence of
      short disintegrins involved the removal of all intronic sequences. The insertion
      position of the intron within Ml_G1, Ml_G2, and Eo_D3 is conserved in the genes
      for vertebrate ADAM (A disintegrin and metalloproteinase) protein disintegrin
      like domains and within the gene for the medium-size snake disintegrins
      halystatins 2 and 3. However, a comparative analysis of currently available
      disintegrin(-like) genes outlines the view that a minimization of both the gene
      organization and the protein structure underlies the evolution of the snake venom
      disintegrin family.

PMID- 17177094
TI  - [Pornography and sexual abuse in the Internet].
AB  - Internet pornography has been regarded as either stimulating sexual aggression
      and abuse or as serving as a safety valve. This controversy is an important issue
      in health, media and legal politics. According to empirical studies on
      pornography in general, soft-core pornography and nonviolent pornography can be
      regarded as harmless, whereas non-violent hard-core pornography and violent
      pornography may increase aggression. Individuals with a high risk for sexual
      aggression show more interest in violent pornography and are stimulated more
      strongly through such material. Two case histories illustrate the characteristics
      of internet pornography and "cybersex": easy access, anonymity, affordability,
      wide range and deviation of the material, unlimited market, blurring the borders
      between consumer and producer, interactive communication, space for experimenting
      between fantasy and in real-life behavior, virtual identities, easy contact
      between offender and victim or among offenders, and low risk of apprehension. The
      phenomenon of "sexual addiction" (or paraphilia- related disorder) is
      particularly relevant for the problematic use of internet pornography. Preventive
      measures to protect possible victims are presented as well as treatment
      strategies for offenders. Beside limiting access to the internet, these include
      therapy of comorbid psychiatric disorders and psychological problems (social
      isolation, bereavement, stress- and anger-management, guilt and shame, childhood
      traumata, cognitive distortion, victim empathy), psychopharmacotherapy and the
      enhancement of a more integrative and relationship-oriented sexuality.

PMID- 17177095
TI  - [Sexuality and pharmacotherapy. Medication-induced disorders of sexual response
      and pharmacotherapeutic options for the treatment of sexual dysfunctions].
AB  - This contribution addresses two different areas of the complex relationship
      between pharmacotherapy and sexual function and dysfunction in men and women. As
      many impairments of sexual function are caused by side effects of medications,
      particularly psychotropic drugs, the first part of the paper describes substances
      and mechanisms often related to sexual dysfunction with a special focus on
      antidepressants and neuroleptics. While serotonin reuptake inhibitors entail a
      high risk of sexual dysfunction, it is often difficult to differentiate the
      negative impact of the drug from the impairment caused by the mental disorder
      itself. Ways to deal with these dysfunctions and remedial measures are discussed.
      In the second section, current pharmacological treatments for female and male
      sexual dysfunctions are reviewed. While there is no approved pharmacotherapy with
      established efficacy for female sexual dysfunction with the possible exception of
      the transdermal testosterone patch for surgically menopausal women, effective
      pharmacological therapies are available for male erectile disorders. In addition,
      testosterone substitution is the treatment of choice for hypoactive sexual desire
      disorders caused by hypogonadism. As sexual dysfunctions are often caused by a
      mixture of psychological and organic factors, treatment strategies combining
      pharmacological options and sex therapy are advocated.

PMID- 17177096
TI  - [Psychotherapy for sexual dysfunctions and desire disorders].
AB  - Sexual problems do not always require specific psychotherapy. If missing or wrong
      sexual information is the main cause, sexual counselling can be sufficient. We
      define "sex-psychotherapy" as the methods which are based on Masters and Johnson
      as well as other symptom-focused and experience- oriented (exercise)
      psychotherapeutic methods for sexually disturbed couples and singles. These
      methods have significantly improved the treatment of sexual dysfunctions. In
      group- and in couple-settings they have proven to be effective in reducing sexual
      symptoms and improving sexual satisfaction and partnership-satisfaction. Long
      term studies showed that sex-psycho- therapy leads to a stable improvement in
      sexual satisfaction, whereas the reduction of sexual symptoms is less stable.
      Therefore sex-psychotherapy should be combined with "relapse-prevention" methods.
      A number of sexual disorders are caused by psychological and organic factors;
      they need both psychotherapy and medical treatment. This is of special importance
      in elderly men and in women with symptoms of dyspareunia.

PMID- 17177097
TI  - [Child sexual abuse].
AB  - The present paper gives an overview on the development of professional discourse
      on sexual abuse over the last 20 years in the field of child protection. After
      the introduction, definitions from different professional perspectives (civil
      law, criminal law, psychotherapy, counseling, etc.) are given. Based on these
      definitions an epidemiological range of prevalence figures is described. In the
      literature, rates ranging from 6 to 25 % in girls and 2 to 8 % in boy as victims
      of sexual abuse can be observed. Psychiatric consequences of sexual abuse are
      described based on an overview of the literature. Diagnostic approaches to
      posttraumatic problems are discussed and distinguished from obsolete measures.
      Some neurobiological findings are presented. Finally the foundations of
      counseling, psychotherapy and pharmacotherapy of behavioral of symptoms and PTSD
      are discussed on the bases of a literature review of controlled clinical trials.
      In conclusion, further developments in psychotherapy and research are discussed
      for the German practical child protection field.

PMID- 17177098
TI  - [Assessment and treatment of sexual offenders].
AB  - Sexual offences are a heterogeneous group of offences that entail very different
      diagnostic categories relevant for key issues of expert assessment. Sexual
      offender trials usually deal with issues related to (diminished) responsibility
      and the necessity of a referral to a forensic psychiatric hospital ( section sign
      63 StGB, German penal code). Furthermore, risk assessment is seen as a necessary
      precondition for relapse prevention and consequently, it forms part of any expert
      assessment in sex offender trials. In terms of treatment, manualized treatment
      programs prevail. Usually they lend themselves to psycho-educative, cognitive
      behavioral and psychodynamic concepts. Notwithstanding the focus of any
      individual program, core elements of all programs pertain to offence related
      (e.g., victim empathy, attitudes and individual values, minimizations, etc.) and
      more general psychotherapy modules (anger management, substance abuse, social
      skills training, etc.). Advantages and disadvantages of these programs are named
      and discussed.

PMID- 17177099
TI  - [Intersexuality. Disorders of sex development].
AB  - Different forms of intersexuality (Disorders of Sex Development, DSD) are
      described (congenital adrenal hyperplasia, androgen insensitivity, disorders of
      androgen biosynthesis, gonadal dysgenesis). Treatment interventions for
      individuals with ambiguous genitalia and untypical sex development are discussed
      with respect to medical and psychosocial aspects considering the consensus paper
      on the management of subjects with intersexuality. The role of gender identity,
      gender role and sexual orientation are presented as well as problems of
      disclosure and gender change. Further research is needed to evaluate the optimal
      treatment procedures.

PMID- 17177100
TI  - [Paraphilia, sexual preference disorders. Diagnosis, etiology, epidemiology,
      treatment and prevention].
AB  - Hostility towards relationships is one prominent characteristic symptom for
      disorders of sexual preference (ICD-10) and paraphilias (DSM-IV). Paraphilic
      symptoms sometimes progress to obsessive or addictive- like forms leading to a
      loss of self-control but can occur also as single incidents or as episodic
      events. Besides constitutional aspects, problems in the development of close
      relationships to primary caregivers (attachment) play an important role in the
      development of these disorders. Actual relationship- and self-confidence problems
      often trigger the severity of disturbance, especially in the episodic forms of
      paraphilia. For patients who are in conflict with the law, cognitive-behavioral
      therapeutic approaches with the aim to minimize self-deception regarding the
      effects of the paraphilic behavior have become more and more relevant. Regarding
      the medical treatment, anti-hormonal therapy plays an important role, but also
      treatment with serotonergic agents and naltrexone are used. Only little can be
      advised in terms of prevention; general psycho-hygiene (regarding the parent
      child relationship) is recommended. Beside these general measures, institutions
      which offer special treatment for people in danger to become delinquents may be
      able to prevent serious harm for possible victims of abuse.

PMID- 17177102
TI  - [Reproduction and psyche].
AB  - Mental health and mental disorders can have a close connection to reproduction,
      especially for women but also for men. The most frequent disorders or problems
      are described, i.e., mental problems during pregnancy and after delivery, during
      the menstrual cycle and around menopause. Possible consequences of miscarriage,
      stillbirth and induced abortion are presented as well as the special problem of a
      wish for a child in mentally ill women and their treatment during pregnancy.

PMID- 17177101
TI  - [Sex education in practice and science in Germany].
AB  - Sex education in Germany has a history full of conflict and ideological change
      between emancipatory, reforming, and repressive tendencies. As a science, sex
      education has only recently gained independence from its mother disciplines
      theology, medicine, psychology, and sociology and at the same time has taken a
      critically constructive position towards sexual science. Its topics range from
      dissemination of knowledge about biological processes and contraception to
      relationship concerns, sexual orientation, gender issues, sexual transgression,
      moral, and ethical questions. Sexual socialization happens nearly everywhere.
      Sexual education takes place mainly in families, elementary education, and
      school, but increasingly also in all other areas of education, social work, and
      health service. Its clientele are no longer exclusively children and adolescents
      but increasingly adults of every age group. Subjects such as AIDS, sexual abuse,
      and teenage pregnancy have contributed to governmental funding of projects and
      training in sex education. Thus, sex education still reaches from mere protection
      from dangers to fostering or maintaining psychological health.

PMID- 17177103
TI  - [Sexual development in the light of socio-cultural changes].
AB  - This article briefly summarizes central components of theories of sexual
      development and outlines that these components depend largely on socio-cultural
      factors. A cultural change of human sexuality is reflected by several phenomena
      such as the public debate about sexual violence and its consequences, a
      diminuation of gender differences and a turn away from monosexuality, tremendous
      changes within the world of partner relationships and a mediatization of
      sexuality. This mediatization is paralleled by a public sexualization as well as
      a de-sexualization of the private sphere together with an increase of a loss of
      sexual desire reflecting well-known problems of human sexuality. Finally, it has
      to be stated that sexuality has experienced a demystification as a consequence of
      socio-cultural changes following the sexual liberalization.

PMID- 17177104
TI  - Enhanced production of ligninolytic enzymes and decolorization of molasses
      distillery wastewater by fungi under solid state fermentation.
AB  - Selected isolates of fungi were grown on wheat straw and corncob in the presence
      of different moistening agents such as water, molasses, potato dextrose broth and
      distillery effluent. All the fungal isolates responded differently with respect
      to growth and ligninolytic enzyme production. Fungal growth on different
      substrates was checked by calculating ergosterol content, which varied widely
      within a single species when grown on different substrates. The maximum laccase
      production was obtained for Aspergillus flavus TERI DB9 grown on wheat straw with
      molasses. For manganese peroxidase, highest production was in Aspergillus niger
      TERI DB20 grown on corncob with effluent. Among the two isolates positive for
      lignin peroxidase, the highest production was in Fusarium verticillioides ITCC
      6140. This immobilized fungal biomass was then used for decolorization of
      effluent from a cane molasses based distillery. Maximum decolorization (86.33%)
      was achieved in Pleurotus ostreatus (Florida) Eger EM 1303 immobilized on corncob
      with molasses in a period of 28 days.

PMID- 17177105
TI  - Subacute motor neuronopathy associated with hepatocellular carcinoma.

PMID- 17177106
TI  - MRI findings of atypical meningioma with microcystic changes.

PMID- 17177107
TI  - Mechanical loading of rigid intramuscular implants.
AB  - Several groups are developing different versions of a new class of leadless,
      permanently implanted electronic devices with a size and form factor that allows
      them to be injected into muscles (BIONs). Their circuitry is protected from body
      fluids by thin-walled hermetic capsules made from rigid and brittle materials
      (glass or ceramic) that include feedthroughs to their electrodes. These packages
      experience repetitive stresses from the very contractions that they excite. We
      here provide a worst-case analysis of such stresses and methods for testing and
      validation of devices intended for such usage, along with the failure analysis
      and remediation strategy for a design that experienced unanticipated failures in
      vivo.

PMID- 17177108
TI  - Seven pregnancies and deliveries from non-mosaic Klinefelter syndrome patients
      using fresh and frozen testicular sperm.
AB  - PURPOSE: The aim of this study was to investigate the feasibility of using frozen
      thawed testicular sperm as well as the timing of testicular sperm extraction
      (TESE) in patients with non-mosaic Klinefelter syndrome. METHODS:
      Intracytoplasmic sperm injection (ICSI) was performed in six of 17 (35%) patients
      whose sperm was recovered by TESE. Multiple biopsies of both testes were
      performed on the day of oocyte retrieval in all but one of the six patients.
      RESULTS: Seven pregnancies and deliveries were achieved in five couples, and one
      couple was unsuccessful. Five pregnancies were achieved using fresh motile sperm,
      and two were achieved using frozen-thawed sperm. Sperm cryopreservation was not
      possible in one of the five couples because of the small number of recovered
      sperm, and possible in four other couples for subsequent ICSI. One woman whose
      husband had TESE performed prior to ovarian stimulation did not become pregnant.
      This may be due to the attainment of only a few immotile sperm following the
      frozen-thawed procedure. CONCLUSION: The outcome of ICSI using fresh or frozen
      thawed testicular sperm in patients with non-mosaic Klinefelter syndrome was
      identical; however, TESE should be performed on the day of oocyte retrieval until
      such time as a procedure with a higher sperm yield from TESE is available.
      Moreover, an improved recovery procedure after cryopreservation-thawing of a
      single spermatozoon must be developed.

PMID- 17177109
TI  - Surgical competence of obstetrics and gynecology residents performing
      microsurgical tubal anastamoses.
AB  - OBJECTIVE: To assess tubal patency rates after microsurgical tubal anastamosis in
      a residency program. STUDY DESIGN: Retrospective cohort analysis. Primary outcome
      measurement was tubal patency rates. RESULTS: Twenty-seven of the forty-nine
      patients (55.1%) had bilateral tubal patency and twenty-one of the forty-nine
      (42.9%) had only one tube open after surgery. No statistical difference in tubal
      patency rate was noted between the REI staff (85.7%) and the resident (71.4%)
      (p=0.09). No statistical difference was noted when comparing the patency rate of
      the residents' first procedure (68.6%) to subsequent procedures (72.8%) (p=0.99).
      CONCLUSIONS: These data suggest that with appropriate guidance, residents without
      prior experience are able to perform microsurgical procedures under direct
      supervision. Residents completed the procedure with patency rates similar to the
      REI staff. Additionally, tubal patency rates were not significant different in
      comparing the residents' first or subsequent procedures.

PMID- 17177110
TI  - LXR alpha transactivates mouse organic solute transporter alpha and beta via IR-1
      elements shared with FXR.
AB  - PURPOSE: Recently identified organic solute transporter (Ost) alpha and beta are
      located on the basolateral membrane of enterocytes and may be responsible for the
      intestinal absorption of many substrates including bile acids. In the present
      study, the mechanism governing the transcriptional regulation of their expression
      was investigated. METHODS AND RESULTS: To clarify the transcriptional regulation
      of Osts, reporter gene assays were performed using mouse Ostalpha/beta promoter
      luciferase reporter constructs. Co-transfection of the constructs with farnesoid
      X receptor (FXR) and retinoid X receptor alpha (RXRalpha) or liver X receptor
      alpha (LXRalpha) and RXRalpha into Caco-2 cells induced the transcriptional
      activities of both Ost alpha and beta and further increases were observed
      following treatment with each agonist. Sequence analyses indicated the presence
      of IR-1 regions in Ostalpha and Ostbeta promoters, which was confirmed by the
      finding that the deletion of IR-1 sequences abolished the response to FXR and
      LXRalpha. Furthermore, mutations in IR-1 reduced the FXR- and LXRalpha-dependent
      transactivation of Ostalpha/beta. Together with the detection of direct binding
      of FXR/RXRalpha and LXRalpha/RXRalpha to the IR-1 elements, the presence of
      functional FXRE/LXRE was revealed in the promoter region of both Ostalpha and
      Ostbeta. In addition, the stimulatory effect of FXR/RXRalpha and
      LXRalpha/RXRalpha on Ostalpha, but not on Ostbeta, was further enhanced by HNF
      4alpha. CONCLUSIONS: It was concluded that LXRalpha/RXRalpha transcriptionally
      regulate mouse Ostalpha/beta via IR-1 elements shared with FXR/RXRalpha. Exposure
      to FXR/LXRalpha modulators may affect the disposition of Ostalpha/beta
      substrates.

PMID- 17177111
TI  - Interaction of omeprazole with a methylated derivative of beta-cyclodextrin:
      phase solubility, NMR spectroscopy and molecular simulation.
AB  - PURPOSE: Cyclodextrins are known to be good solubility enhancers for several
      drugs, improving bioavailability when incorporated in pharmaceutical
      formulations. In this work we intend to assess and characterize the formation of
      inclusion complexes between omeprazole (OME) and a methylated derivative of beta
      cyclodextrin, methyl-beta-cyclodextrin (MbetaCD). A comparison with results
      obtained from the most commonly used natural cyclodextrin, beta-cyclodextrin
      (betaCD) is also presented in most cases. MATERIALS AND METHODS: The interaction
      of OME with the mentioned cyclodextrins in aqueous solutions was studied by phase
      solubility studies, 1D (1)H and 2D rotating frame nuclear overhauser effect NMR
      spectroscopy (ROESY) and Molecular Dynamics. RESULTS: The solubility of OME was
      significantly increased by formation of inclusion complexes with each
      cyclodextrin. Phase solubility studies and continuous variation plots revealed
      that OME forms an inclusion complex in a stoichiometry of 1:1 with both
      cyclodextrins. (1)H NMR and ROESY spectra of the inclusion complexes indicated
      that the benzimidazole moiety is included within the cyclodextrins cavities.
      Molecular dynamics showed that OME is more deeply included in the MbetaCD than in
      betaCD cavity, in agreement with a larger apparent stability constant (K (S))
      obtained for the inclusion complex with MbetaCD. CONCLUSIONS: MbetaCD proved to
      be an efficient enhancer of OME solubility, thus possessing characteristics for
      being an useful excipient in pharmaceutical formulations of this drug.

PMID- 17177113
TI  - Influence of processing conditions on the physical state of mannitol-
      implications in freeze-drying.
AB  - PURPOSE: To study the effect of processing conditions on the physical state of
      mannitol during various stages of the lyophilization cycle of a protein
      formulation. MATERIALS AND METHODS: Mannitol and trehalose were used as the
      bulking agent and lyoprotectant, respectively. The physical state of mannitol
      during various stages of freeze-drying cycle, in the absence and presence of a
      model protein, was characterized using low temperature X-ray powder
      diffractometry (XRD) and differential scanning calorimetry (DSC). RESULTS:
      Mannitol did not crystallize even when the solution for lyophilization was cooled
      to -45 degrees C at a slow cooling rate of 1 degree C/min. Annealing facilitated
      mannitol crystallization, and in the absence of the protein, a mixture of delta
      mannitol and mannitol hemihydrate was obtained at both low (-18 degrees C) and
      high (-8 degrees C) annealing temperatures. However, in the presence of protein,
      the high annealing temperature promoted delta-mannitol crystallization and
      inhibited formation of mannitol hemihydrate, while the low annealing temperature
      facilitated the formation of mannitol hemihydrate. Interestingly, the hemihydrate
      in the frozen solution was retained in the final lyophile, even when the primary
      and secondary drying temperatures were as high as -5 and 65 degrees C,
      respectively. CONCLUSIONS: The presence of protein as well as the processing
      conditions (annealing temperature and time, primary and secondary drying
      temperatures) influenced the physical form of mannitol in the final lyophile. The
      protein promoted formation of delta-mannitol while inhibiting the formation of
      mannitol hemihydrate. Since the physical form of mannitol was greatly influenced
      by the presence of protein, it will be prudent to conduct the preliminary
      lyophilization cycle development studies in the presence of the protein. If
      mannitol hemihydrate is formed during annealing, its dehydration may require high
      secondary drying temperature.

PMID- 17177114
TI  - Influence of realistic inspiratory flow profiles on fine particle fractions of
      dry powder aerosol formulations.
AB  - PURPOSE: The purpose of the study was to determine how air flow profiles affect
      fine particle fractions (FPF) (<5 microm) from dry powder aerosol formulations
      and whether laser diffraction (LD) could be used to measure FPF of aerosols
      generated by variable flows. MATERIALS AND METHODS: Carrier-based formulations
      containing 1.5% w/w micronized salbutamol base blended with the 63-90 microm
      fraction of alpha-lactose monohydrate or sorbitol or maltose were aerosolised
      from a model glass device using either a constant flow rate or a predetermined
      flow profile. The FPFs of the same aerosolised particles were first measured by
      LD and then by a liquid impinger. Volunteer inhalation airflow profiles and 3
      phase (acceleration, constant flow rate and deceleration) square wave airflow
      profiles were generated using the Electronic Lung and an Inhalation Profile
      Recorder. Similar experiments were conducted for a carrier-free formulation from
      the Bricanyl Turbohaler. RESULTS: Salbutamol FPFs of all carrier-based
      formulations were found to increase by increasing the initial flow increase rate
      (FIR) from 200 to 600 l min(-1) s(-1) although they could be placed in an
      increasing order of maltose blend < sorbitol blend < lactose blend. A significant
      linear correlation was found between FPFs measured by LD and by inertial
      impaction (R (2) = 0.95, p < 0.01, ANOVA). For the Bricanyl Turbohaler,
      increasing FIR from 120 to 600 l min(-1) s(-1) for a constant peak flow rate
      (PFR) of 60 l min(-1) increased the mean Terbutaline FPF from 18.2% to 45.5%. For
      the volunteer inhalation profiles, a higher FIR tended to be associated with
      higher PFR, leading to a marked increase in drug FPF due to the combined effect
      of FIR and PFR. CONCLUSION: Drug FPF from either carrier-free or carrier-based
      formulations is determined by both FIR and PFR. LD is a viable technique to
      measure the performance of dry powder aerosol formulations at realistic
      inspiratory flow profiles.

PMID- 17177112
TI  - Influence of drug transporter polymorphisms on pravastatin pharmacokinetics in
      humans.
AB  - The role of drug transporters in pravastatin disposition is underlined by the
      fact that pravastatin does not undergo significant cytochrome P-450 (CYP)
      mediated biotransformation. The organic anion transporting polypeptide 1B1
      (OATP1B1), encoded by SLCO1B1, and multidrug resistance-associated protein 2
      [MRP2 (ABCC2)], are thought to be the major transporters involved in the
      pharmacokinetics of pravastatin in humans. Other transporters that may play a
      role include OATP2B1, organic anion transporter 3 (OAT3), bile salt export pump
      (BSEP), and the breast cancer resistance protein (BCRP). OATP1B1 and MRP2 mediate
      the hepatic uptake and biliary excretion of pravastatin, respectively. The
      SLCO1B1 and ABCC2 polymorphisms probably contribute to the high interindividual
      variability in pravastatin disposition. Recent small studies have characterized
      the impact of the SLCO1B1 polymorphism on pravastatin in humans, and especially
      the c.521T>C single-nucleotide polymorphism (SNP) seems to be an important
      determinant of pravastatin pharmacokinetics. Pravastatin plasma concentrations
      may be up to 100% higher in subjects carrying the c.521C variant, as found in the
      *5, *15, *16, and *17 haplotypes, reflecting diminished OATP1B1-mediated uptake
      into the major site of pravastatin elimination, the liver. The SLCO1B1
      polymorphism seems to have a similar impact on the pharmacokinetics of single-
      and multiple-dose pravastatin. Overall, 2-5% of individuals in various
      populations may be expected to show markedly elevated plasma pravastatin
      concentrations due to the SLCO1B1 polymorphism. Of note, the impact of the
      SLCO1B1 polymorphism on statins may be dependent on ethnicity. Although
      individuals with a diminished hepatic uptake of pravastatin might be expected to
      show reduced cholesterol-lowering efficacy due to lower intracellular pravastatin
      concentrations, there is preliminary evidence to suggest that the SLCO1B1
      polymorphism is not a major determinant of non-response to pravastatin. The
      possible consequences of drug transporter polymorphisms, especially the SLCO1B1
      and ABCC2 polymorphisms, for the lipid-lowering efficacy and tolerability of
      pravastatin in various ethnic groups warrant further study.

PMID- 17177115
TI  - Noonan syndrome and related disorders: alterations in growth and puberty.
AB  - Noonan syndrome is a relatively common multiple malformation syndrome with
      characteristic facies, short stature and congenital heart disease, most commonly
      pulmonary stenosis (Noonan, Clin Pediatr, 33:548-555, 1994). Recently, a mutation
      in the PTPN11 gene (Tartaglia, Mehler, Goldberg, Zampino, Brunner, Kremer et al.,
      Nat Genet, 29:465-468, 2001) was found to be present in about 50% of individuals
      with Noonan syndrome. The phenotype noted in Noonan syndrome is also found in a
      number of other syndromes which include LEOPARD (Gorlin, Anderson, Blaw, Am J Dis
      Child, 17:652-662, 1969), Cardio-facio-cutaneous syndrome (Reynolds, Neri,
      Hermann, Blumberg, Coldwell, Miles et al., Am J Med Genet, 28:413-427, 1986) and
      Costello syndrome (Hennekam, Am J Med Genet, 117C(1):42-48, 2003). All three of
      these syndromes share similar cardiac defects and all have postnatal short
      stature. Very recently, HRAS mutations (Aoki, Niihori, Kawame, Kurosawa, Ohashi,
      Tanaka et al., Nat Genet, 37:1038-1040, 2005) have been found in the Costello
      syndrome and germline mutations in KRAS and BRAF genes (Rodriguez-Viciana, Tetsu,
      Tidyman, Estep, Conger, Santa Cruz et al., Nat Genet, 2006; Niihori, Aoki,
      Narumi, Neri, Cave, Verloes et al., Nat Genet, 38:294-296, 2006) in the Cardio
      facio-cutaneous syndrome. Phenotypic overlap between these genetic disorders can
      now be explained since each is caused by germline mutations that are major
      components of the RAS-MAPK pathway. This pathway plays an important role in
      growth factor and cytokine signaling as well as cancer pathogenesis.

PMID- 17177116
TI  - Effects of mild early life stress on abnormal emotion-related behaviors in 5-HTT
      knockout mice.
AB  - A low-expressing polymorphic variant of the serotonin transporter (5-HTT) gene
      has been associated with emotional disorders in humans and non-human primates
      following exposure to early life trauma. 5-HTT gene knockout (KO) mice exhibit
      increased anxiety- and depression-related behaviors, and provide a model to study
      interactions between 5-HTT gene variation and early life stress. The present
      study assessed the effects of postnatal footshock stress on the development of
      emotion-related behaviors in 5-HTT KO mice. Results showed that 5-HTT KO mice
      displayed a profile of suppressed exploratory behavior and increased anxiety-like
      behavior in the light/dark, elevated plus-maze and open field tests, as well as
      increased depression-related behavior in the forced swim test following repeated
      exposure to the test. Postnatal exposure to footshock stress did not affect
      emotion-related behaviors in non-mutant C57BL/6J mice or modify phenotypic
      abnormalities in 5-HTT KO. Data provide further evidence of emotional
      abnormalities following genetic disruption of the 5-HTT.

PMID- 17177117
TI  - Sex differences in the pathway from low birth weight to
      inattention/hyperactivity.
AB  - Inattention/hyperactivity is a childhood outcome of low birth weight. However,
      the mechanisms by which low birth weight leads to inattention/hyperactivity are
      unclear. This study examined arousal, activation, motor speed, and motor
      coordination as possible mechanisms, attending to sex differences. 823 children
      (400 males) from Detroit and surrounding suburbs were assessed with the Child
      Behavior Checklist and the Teacher Report Form and completed experimental tasks
      to assess vigilance and activation (Continuous Performance Test signal detection
      parameters) and motor output speed and control (Grooved Pegboard) at 6 years of
      age. The relationship between birth weight and inattention/hyperactivity was
      slightly, but not significantly, stronger for boys than for girls. Arousal, motor
      speed, and motor coordination significantly partially mediated the relationship
      between birth weight and inattention/hyperactivity for boys and girls. Moderated
      mediation was found for the pathway between motor coordination and
      inattention/hyperactivity such that this relationship was stronger for boys than
      for girls. Sex differences in the associated features of attention symptoms may
      reflect partially distinct etiological pathways.

PMID- 17177119
TI  - Vicarious futurity in autism and childhood dementia.
AB  - Vicarious futurity is the hope and despair that a person has for another's
      future. This study examined the vicarious futurity of parents of children with
      autism and childhood dementia. Participants were 22 parents of children with
      autism and 7 parents of children with childhood dementia. Variability in levels
      of vicarious hope and vicarious despair was found highlighting the complexity of
      vicarious futurity. Results indicated that levels of vicarious hope and vicarious
      despair and the association between the two constructs are likely to have greater
      explanatory value than either construct considered on its own or a global score
      that combines both. Directions for further research are discussed.

PMID- 17177120
TI  - Ultrasound findings in adductor related groin pain.

PMID- 17177118
TI  - Poor facial affect recognition among boys with duchenne muscular dystrophy.
AB  - Children with Duchenne or Becker muscular dystrophy (MD) have delayed language
      and poor social skills and some meet criteria for Pervasive Developmental
      Disorder, yet they are identified by molecular, rather than behavioral,
      characteristics. To determine whether comprehension of facial affect is
      compromised in boys with MD, children were given a matching-to-sample test with
      four types of visual recognition (Object, Face, Affect, and Situation matching)
      developed by Lucci and Fein. Within-group analyses on 50 boys with MD found
      decreased Affect matching relative to the other matching conditions. Between
      group comparisons on 20 sibling pairs found the boys with Duchenne performed more
      poorly only on the Affect-matching condition. Thus, mildly impaired facial affect
      recognition may be part of the phenotype associated with Duchenne or Becker MD.

PMID- 17177122
TI  - Ultrasound of venous thrombosis of the leg.

PMID- 17177124
TI  - Report of Euroson 2006.

PMID- 17177133
TI  - Choleretic effects of the Mongolian medicinal plant Saussurea amara in the
      isolated perfused rat liver.
AB  - Saussurea amara is used in traditional Mongolian medicine for the treatment of
      hepato-biliary disorders. To determine the plant's effect on the bile-salt
      independent bile flow (hydrocholeresis) as a measure of liver exocrine functions,
      different extracts were investigated in the isolated rat liver perfusion system.
      The methanolic extract (3) exerted a dose-dependent increase in bile flow (16%,
      37%, 53%, 61%) in concentrations of 50 mg/L, 100 mg/L, 250 mg/L and 500 mg/L. The
      aqueous crude extract (1) and the ethyl acetate extract (2) also showed a dose
      dependent increase, whereas at the highest concentrations (1000 mg/L and 100
      mg/L, respectively) a continuous decrease in bile flow could be observed.
      Cynaropicrin also provoked a dose-dependent increase in bile flow, but caused
      liver damage at the highest dose tested (20 mg/L). Apigenin 7- O-glucoside,
      present in extracts 2 and 3, induced a dose-dependent increase of 20%, 30% and
      40% (5 mg/L, 10 mg/L, 20 mg/L) and showed a significantly higher effect than the
      reference substance cynarin. The total flavonoid content was determined by
      spectrophotometry. To quantify the absolute amount of cynaropicrin in the crude
      drug and in the tested extracts, an HLPC system was established with santonin as
      internal standard.

PMID- 17177135
TI  - Changes and relations of circulating visfatin, apelin, and resistin levels in
      normal, impaired glucose tolerance, and type 2 diabetic subjects.
AB  - Visfatin and apelin are two novel adipocyte- secreted hormone proposed to link
      obesity with insulin resistance. In this study we investigated whether plasma
      visfatin and apelin levels were altered in normal, impaired glucose tolerance,
      and type 2 diabetic subjects. We also assessed the association between plasma
      visfatin, or apelin and body composition, metabolic parameters, and resistin
      concentrations in these subjects. The visfatin levels of fasting and 2-h post
      glucose load were found to be significantly decreased in diabetics compared with
      the controls ( P<0.05). In contrast, basal apelin levels were significantly
      increased in the IGT and diabetic subjects compared with the controls ( P<0.05
      and P<0.01). The apelin levels of 2-h post-glucose load were significantly higher
      than the basal levels in every group (all P<0.05). Fasting plasma visfatin was
      found to correlate positively and significantly with BMI, WHR, and fasting plasma
      resistin, but negatively with HbA1c and 2 h OGTT glucose. Multiple regression
      analysis showed that WHR, HbA1c, 2 h OGTT glucose were independent related
      factors influencing plasma visfatin levels. Fasting plasma apelin levels
      correlated positively with HOMA-IR, BMI, TC, LDL-C, FBG and Fasting plasma
      insulin. Multiple regression analysis also showed that HOMA-IR, BMI, and TC were
      independent related factors influencing plasma apelin levels. The present work
      indicates the potential link of visfatin and apelin with the pathogenesis of
      insulin resistance and T2DM.

PMID- 17177134
TI  - Assessment of basal insulin requirement using fasting tests in insulin-treated
      patients with type 2 diabetes mellitus.
AB  - AIMS: Characterizing the time course of the rise of blood glucose concentrations
      in the fasting state during the day and night in patients with type 2 diabetes.
      METHODS: 40 consecutive insulin-treated patients with type 2 diabetes underwent
      fasting tests on two different days with either no breakfast and lunch (fasting
      time of 20 hours) or no dinner (fasting time of 21 hours). Glucose-lowering
      medication was stopped prior to the test according to the half-life of the
      medication prescribed. At the start of the fasting tests, blood glucose
      concentrations were lowered to below 7 mmol/L using an insulin infusion. RESULTS:
      26 men and 14 women were included in the study. Mean (+/-SD) age was 61+/-10
      years, BMI 31+/-7 kg/m (2), and HbA1c 7.5+/-1%. Diabetes duration was 14+/-8
      years and duration of insulin therapy had been prescribed for a mean of 6+/-6
      years. During the daytime fast, plasma glucose concentrations rose by a mean of
      0.8+/-1.6 mmol/L. During the nighttime fast, plasma glucose concentrations
      increased particularly after midnight, by 4.3+/-2.1 mmol/L, i.e. significantly
      more than during the daytime fast. CONCLUSIONS: Fasting blood glucose
      concentrations in the majority of insulin-treated patients with type 2 diabetes
      increase markedly after midnight. No similar increase is observed during the day.
      Thus, for most patients with type 2 diabetes, an intermediate- or long-acting
      insulin injected at bedtime with a peak action six to eight hours after injection
      should be appropriate.

PMID- 17177136
TI  - Impact of maternal diabetes mellitus on the thermoregulation of the offspring.
AB  - Maternal diabetes mellitus (DM) can induce metabolic alterations in both newborn
      and adult offspring. It is believed that inadequate intrauterine conditions can
      impair thermogenic capacity of the offspring. The objective of the present study
      was to evaluate the effects of maternal DM on the offspring thermoregulation. DM
      was induced by streptozotocin injection (60 mg/g) in Wistar EPM-1 female rats.
      Control animals were injected with an equal volume of citrate buffer solution (pH
      4.5). Fifteen days after confirmation of diabetes by glycaemia higher than 250
      mg/dl, the rats were mated and the intercourse was confirmed by vaginal smear.
      Diabetic animals received daily 1 UI of insulin and control animals, an
      equivalent volume of saline. After delivery, 6 newborn females were randomly
      assigned to each mother in order to assure equivalent nutritional status during
      lactation during which body weight of the offspring was recorded daily. At
      weaning (28th day) the animals were transferred to individual metallic cages kept
      inside a chamber under a room temperature of 25 degrees C. In the 60th day, half
      of the offspring was moved to a chamber at 5 degrees C, remaining there until the
      90th day. Four experimental groups were thus formed that were the offspring of
      control or diabetic dams acclimated at 25 degrees C or 5 degrees C. During the
      whole experimental period body weight and food intake were recorded and during
      the acclimation period energy balance was determined. When rats were 90 days-old,
      they were blood sampled and the carcasses prepared for calorimetric
      determination. At birth, weaning and 90 days of age, animals were killed for
      quantification of body fat, protein and water. Blood samples were collected and
      used to determine blood glucose and insulin. Offspring from diabetic dams showed
      lower body weight than controls throughout the whole experiment. No effect of
      maternal DM on energy balance of offspring acclimated at 25 degrees C or at 5
      degrees C was observed. Nevertheless, as expected, cold induced an increase in
      energy intake and energy expenditure as well as a reduction in food efficiency,
      which was characterized by lower body weight and fat gain without change in body
      protein. Body composition was altered only at birth, when animals from diabetic
      mothers showed decreased body fat content and increased percentage of water in
      the carcass. Only at 90 days the rats from diabetic mothers showed higher
      glycaemia and lower blood insulin levels than controls suggesting delayed effects
      of maternal DM on the offspring. After weaning, rectal temperature of the animals
      was measured at 25 degrees C and 5 degrees C during 2 hours at time 0, 30, 60,
      90, and 120 minutes. This parameter was determined at weaning and at 45, 60, 75,
      and 90 days of age. The results showed that the offspring from diabetic mothers
      not only had a delayed thermogenic capacity as shown by their inability to keep
      body temperature at 5 degrees C until 90 days. It is, thus, suggested that
      maternal diabetes mellitus delayed thermoregulation of the offspring.

PMID- 17177137
TI  - Osteopontin deficiency impacts the pancreatic TH1/TH2 cytokine profile following
      multiple low dose streptozotocin-induced diabetes.
AB  - Osteopontin (OPN) is a phosphorylated acidic glycoprotein that causes chemotaxis
      of macrophages and downregulation of nitric oxide synthesis. OPN has been shown
      to be involved in the pathogenesis of autoimmune diseases. Here, we tested the
      hypothesis that increased expression of pancreatic OPN in experimental diabetes
      has a protective role. The immune response phenotype associated with the
      induction of diabetes was evaluated in male OPN knockout (KO) and wild type (WT)
      mice. Multiple low dose streptozotocin (STZ) (MLDS), 40 mg/kg, was injected
      intraperitoneally for 5 days to establish a model for autoimmune diabetes.
      Glucose levels and body weight were evaluated in the vehicle and STZ treated
      groups. ELISA assay was used to monitor OPN serum levels in the WT diabetic mice.
      Histological studies evaluated insulitis development and Western blot analysis
      was employed to evaluate the expression levels of Th1 cytokines (TNF-alpha and
      IFN-gamma) and Th2 cytokines (IL-10 and IL-4). Immunohistochemistry was employed
      to localize IL-4 in the diabetic WT pancreata. Both WT and KO mice developed
      diabetes. In the WT, OPN serum levels were significantly upregulated 1 day after
      STZ injection. Pancreatic islets appeared larger in the KO group. Mild
      lymphocytic infiltrate and apoptosis were detected in the WT diabetic islets,
      while no signs of inflammation were detected in the KO group. WT diabetics showed
      upregulation of both Th1 and Th2 cytokines, whereas in the diabetic KO a mild
      upregulation of Th1 cytokines was detected with significant downregulation of IL
      4. In the diabetic WT mice, IL-4 was localized in the interlobular connective
      tissue. Our studies show that the pancreatic immune response to MLDS diabetes is
      balanced between the Th1 and Th2 in the WT animals. KO mice show mild
      polarization towards the Th1 response. Although OPN is a known promoter for Th1
      responses, it appears to have a regulatory control over the Th2 response in MLDS.

PMID- 17177138
TI  - Protective effect of Gui Qi mixture on the progression of diabetic nephropathy in
      rats.
AB  - Huang Qi (root of Astragalus membranaceus) and Dang Gui ( Angelica sinensis), two
      of the most widely used herbs in traditional Chinese medicine, have been proven
      to be effective in the treatment of diabetes mellitus (DM) although the
      underlying molecular mechanisms are not fully elucidated. This study was designed
      to investigate the protective effect of Dang Gui and Huang Qi mixture (GQM) on
      the development of diabetic nephropathy in rats with streptozotocin (STZ)-induced
      DM and the possible underlying molecular mechanism. The diabetic animal model was
      made by a single intraperitoneal injection of STZ and then treated with GQM or
      benazepril. Blood glucose, triglyceride (TG), cholesterol (CHO), high density
      lipoprotein (HDL), serum creatinine (Scr), creatinine clearance rate (Ccr), blood
      urea nitrogen (BUN), urine beta (2)-microglobin (beta (2)-MG), kidney/body weight
      (K/B) ratio, glomerular area (GA), renal transforming growth factor-beta (1) (TGF
      beta (1)) mRNA expression and blood and renal angiotensin II (AngII) expression
      were determined 8 weeks after the treatment. The blood glucose, CHO and TG
      levels, BUN, SCr, Ccr. K/B ratio, GA, the excretion of beta (2)-MG, renal TGF
      beta (1) mRNA expression and blood and renal AngII expression were significantly
      increased while the HDL level was decreased 8 week after STZ injection. The
      changes in blood glucose, TG, CHO and HDL were reversed by GQM, not by
      benazepril, whereas the changes in other variables were reversed by both GQM and
      benazepril. Our results suggest that GQM alleviates the disorder in blood glucose
      and lipids, protects against the progression of renal nephropathy in diabetic
      rats, probably by inhibiting the expression of AngII and TGF-beta (1) mRNA.

PMID- 17177139
TI  - A novel mutation (E333D) in the thyroid hormone beta receptor causing resistance
      to thyroid hormone syndrome.
AB  - Resistance to thyroid hormone (RTH) is an inherited syndrome characterized by
      elevated serum thyroid hormones (TH), failure to suppress pituitary thyroid
      stimulating hormone (TSH) secretion, and variable peripheral tissue
      responsiveness to TH. The disorder is associated with diverse mutations in the
      thyroid hormone beta receptor (TRbeta). Here, we report a novel natural RTH
      mutation (E333D) located in the large carboxy-terminal ligand binding domain of
      TRbeta. The mutation was identified in a 22-year-old French woman coming to
      medical attention because of an increasing overweight. Biochemical tests showed
      elevated free thyroxine (T4: 20.8 pg/ml (normal, 8.5-18)) and triiodothyronine
      (T3: 5.7 pg/ml (normal, 1.4-4)) in the serum, together with an inappropriately
      nonsuppressed TSH level of 4.7 mU/ml (normal, 0.4-4). Her father and her
      brother's serum tests also showed biochemical abnormalities consistent with RTH.
      Direct sequencing of the TRbeta gene revealed a heterozygous transition 1284A>C
      in exon 9 resulting in substitution of glutamic acid 333 by aspartic acid residue
      (E333D). Further functional analyses of the novel TRbeta mutant were conducted.
      We found that the E333D mutation neither significantly affected the affinity of
      the receptor for T3 nor modified heterodimer formation with retinoid X receptor
      (RXR) when bound to DNA. However, in transient transfection assays, the E333D
      TRbeta mutant exhibited impaired transcriptional regulation on two distinct
      positively regulated thyroid response elements (F2- and DR4-TREs) as well as on
      the negatively regulated human TSHalpha promoter. Moreover, a dominant inhibition
      of the wild-type TRbeta counterpart transactivation function was observed on both
      a positive (F2-TRE) and a negative (TSHalpha) promoter. These results strongly
      suggest that the E333D TRbeta mutation is responsible for the RTH phenotype in
      the proposita's family.

PMID- 17177140
TI  - Low serum 25-hydroxyvitamin D concentrations are associated with insulin
      resistance and obesity in women with polycystic ovary syndrome.
AB  - Insulin resistance (IR) and central obesity are common features of the polycystic
      ovary syndrome (PCOS). Vitamin D is thought to play a role in the pathogenesis of
      type 2 diabetes by affecting insulin metabolism. The aim of our study was to
      investigate the effect of 25-hydroxyvitamin D (25-OH-VD) on metabolic parameters
      and IR in PCOS. In 120 untreated PCOS patients (median age 28 years) levels of 25
      OH-VD (radioimmunoassay method provided by DiaSorin), calcium and anorganic
      phosphate were measured. In addition, endocrine and metabolic variables were
      evaluated and a glucose tolerance test was performed to assess indices of IR. In
      the entire PCOS cohort, 25-OH-VD concentrations were negatively correlated with
      body mass index (r=-0.2765), body fat (r=-0.2490), HOMA-IR (r=-0.1947),
      hyperinsulinemia (r=-0.1892) and leptin levels (r=-0.2834), and positively
      correlated with HDL cholesterol (r=0.2630) (all p<0.05). Subgroup analysis of
      lean, overweight and obese women revealed significant higher 25-OH-VD levels in
      lean women. Differences remained significant when women were divided according to
      their 25-OH-VD levels. Women with hypovitaminosis D (<9 ng/ml) had higher mean
      BMI, indices of IR and leptin levels compared to women with normal serum levels
      (all p<0.05). Analysis of vitamin D and biochemical endocrine PCOS features
      revealed a significant correlation only between 25-OH-VD and sex hormone-binding
      globulin as well as the free androgen index. In conclusion, in PCOS women, low 25
      OH-VD levels are associated with obesity and insulin resistance but not with PCOS
      per se.

PMID- 17177141
TI  - Expression and distribution of prolactin receptor in normal, fibrotic, and
      cirrhotic human liver.
AB  - Liver cirrhosis is often associated with elevated levels of prolactin (PRL). This
      is commonly attributed to impaired hepatic metabolism of estrogens. However,
      there is evidence suggesting that PRL may be an important factor in hepatic
      tissue regeneration. To investigate the role of PRL in the pathogenesis of liver
      cirrhosis, we used RT-PCR and immunhistochemical staining to analyze changes in
      the expression and the histological distribution of the prolactin receptor (PRLR)
      in normal, fibrotic and cirrhotic hepatic tissue. Liver tissue was obtained from
      29 surgically explanted human livers. The histological examination demonstrated
      normal liver tissue (n=9) as well as different grades of fibrosis (n=10) and
      cirrhosis (n=10). In liver cirrhosis and fibrosis, PRLR-mRNA was expressed at a
      higher level compared to normal liver specimens. Immunohistochemical staining of
      normal liver tissue demonstrated homogeneous distribution of the PRLR in the
      hepatocytes and in the epithelial cells of the bile ducts. This pattern of
      distribution was lost in fibrosis, where an accumulation of the PRLR was observed
      in the damaged hepatocytes. As no PRL-mRNA was detectable in normal, fibrotic or
      cirrhotic tissue, PRL does not act through autocrine or paracrine mechanisms.
      These data confirm previous results, which we obtained using an animal model for
      experimental liver cirrhosis in rats suggesting a metabolic function of PRL in
      normal liver and a regenerative function in fibrotic and cirrhotic liver. In
      conclusion, PRL might be involved in the pathogenesis of liver cirrhosis.

PMID- 17177142
TI  - Expression of Eph receptor tyrosine kinases and their ligands in human Granulosa
      lutein cells and human umbilical vein endothelial cells.
AB  - Corpus luteum development is regulated by gonadotropins and accompanied by
      extremely rapid vascularization of the avascular granulosa cell compartiment by
      endothelial cells (EC). The proliferation of Granulosa cells (GC) and EC is a
      complex interplay and takes place in a spatially and temporarily coordinated
      manner. The erythropoietin-producing hepatoma amplified sequence (Eph) receptors
      and their ligands-the ephrins- are a recently detected family of membrane located
      protein tyrosine kinases which play a crucial role in the growth and development
      of nerve and blood vessel network. We report about the mRNA expression pattern of
      Ephs and their ligands in human GC, in human EC, and in carcinoma cell lines
      OvCar-3 and Hela. The mRNA of EphA4, EphA7, ephrinA4, ephrinB1 and ephrinB2 was
      detected in GC and EC, while EphA2 was expressed only in GC. The expression of
      various Ephs and ephrins did not change in GC after stimulation with human
      chorion gonadotropin. Our study analyzes for the first time the expression of the
      complete human Eph/ephriny-system in GC and in EC. The remarkable similarity
      between these two cell types supports the theory of a functional relationship of
      EC and GC. In addition, it was shown that hCG is not a major determinant of
      Eph/ephrin regulation in GC.

PMID- 17177143
TI  - Severe hypernatraemia due to nephrogenic diabetes insipidus - a life-threatening
      side effect of chronic lithium therapy.
AB  - Renal toxicity of long-term lithium therapy is a common problem. Nephrogenic
      diabetes insipidus is the most frequently encountered complication, but often
      remains unrecognised because of the rather benign symptoms. We present a patient
      with long-term lithium therapy who developed life-threatening hypernatraemia due
      to insufficient oral fluid intake after elective spinal surgery. Careful daily
      substitution of up to 25 l of hypotonic fluids led to full recovery within 9
      days. Nephrogenic diabetes insipidus should always be considered in lithium
      treated patients undergoing elective surgery in order to avoid severe
      hypernatraemia.

PMID- 17177144
TI  - Serum soluble factors induce the proliferation, alkaline phosphatase activity and
      transforming growth factor-beta signal in osteoblastic cells in the patient with
      hepatitis C-associated osteosclerosis.
AB  - Hepatitis C-associated osteosclerosis (HCAO) is a rare syndrome characterized by
      severe, acquired, generalized osteosclerosis and hyperostosis in adults who are
      infected with the hepatitis C virus. However, the detail of the pathogenesis of
      HCAO is still unknown. We examined the effects of serum of the HCAO patient on
      the proliferation, alkaline phosphatase (ALP) activity and transforming growth
      factor (TGF)-beta-Smad signaling in mouse osteoblastic cells. The patient was
      compatible with HCAO, characterized by high bone mass, bone thickening and bone
      pain with normal lamelar bone. The serum from the HCAO patient increased the
      levels of TGF-beta and Smad3 expression in osteoblastic MC3T3-E1 cells, compared
      with the control subject. Moreover, the serum from the HCAO patient significantly
      augmented TGF-beta-induced transcriptional activity with luciferase assay using
      3TP-Lux with a Smad3-specific responsive element. In addition, the serum from the
      HCAO patient significantly stimulated the MTT intensity, the level of
      proliferating cell nuclear antigen expression, a proliferation marker, and ALP
      activity in MC3T3-E1 cells, compared with that from the control subject. In
      conclusion, the present study indicated that the serum from the HCAO patient
      stimulated TGF-beta-Smad signaling, as well as the proliferation and ALP activity
      in osteoblastic cells. Some soluble factors other than parathyroid hormone might
      be related to the pathogenesis of HCAO.

PMID- 17177145
TI  - Congress report from the American Diabetes Association 66th Annual Scientific
      Sessions in Washington, USA.

PMID- 17177146
TI  - Early onset multiple sclerosis: more emphasis on early treatment.

PMID- 17177147
TI  - Natural history of Canavan disease revealed by proton magnetic resonance
      spectroscopy (1H-MRS) and diffusion-weighted MRI.
AB  - Canavan disease is a childhood leukodystrophy caused by mutations in the gene for
      human aspartoacylase ( ASPA), which leads to an abnormal accumulation of the
      substrate molecule N-acetyl-aspartate (NAA) in the brain. This study was designed
      to model the natural history of Canavan disease using MRI and proton magnetic
      resonance spectroscopy ( (1)H-MRS). NAA and various indices of brain structure
      (morphology, quantitative T1, fractional anisotropy, apparent diffusion
      coefficient) were measured in white and gray matter regions during the
      progression of Canavan disease. A mixed-effects statistical model was used to fit
      all outcome measures. Longitudinal data from 28 Canavan patients were directly
      compared in each brain region with reference data obtained from normal, age
      matched pediatric subjects. The resultant model can be used to non-invasively
      monitor the natural history of Canavan disease or related leukodystrophies in
      future studies involving drug, gene therapy, or stem cell treatments.

PMID- 17177148
TI  - Analysis of MxA, IL-4, and IRF-1 genes in Filipino patients with subacute
      sclerosing panencephalitis.
AB  - BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a chronic and
      debilitating disease of the central nervous system caused by a latent measles
      virus infection. Three candidate genes, MxA, IL-4, and IRF-1 genes were shown to
      be associated with SSPE in Japanese patients. These genes have been suggested to
      play a role in the establishment of persistent viral infection in the central
      nervous system. SUBJECTS AND METHODS: Sixty Filipino SSPE patients and 120
      healthy control subjects were included in the study. Single nucleotide
      polymorphisms at promoter regions ( IL-4-590C/T and MXA-88G/T) were screened
      using PCR-RFLP method. Genotyping was done for GT repeat polymorphism within
      intron 7 of IRF-1. RESULTS: The TT genotype of MXA, as well as the CT genotype of
      IL-4, were seen a little more frequently among the SSPE patients as compared to
      the control subjects. The values though, did not reach statistical significance.
      IRF-1 analysis did not differ between the two groups. CONCLUSION: Our study
      failed to demonstrate a significant association between IL-4, MXA, or IRF-1, and
      SSPE in the Filipino population. Our results might be explained by a greater
      contribution of environmental factors such as the socio-economic and nutritional
      factors in the susceptibility of Filipinos to SSPE other than genetic factors.

PMID- 17177149
TI  - Topiramate: a new agent for patients with alternating hemiplegia of childhood.
AB  - Alternating hemiplegia of childhood is a rare syndrome characterized by the
      onset, before 18 months of age, of frequent attacks of alternating paralysis.
      Here we report the efficacy of topiramate in four patients with alternating
      hemiplegia of childhood (AHC) that did not respond to flunarizine, as well as in
      two newly diagnosed patients. Following treatment with topiramate, the frequency
      and duration of hemiplegic attacks significantly improved in all patients.
      Additional symptoms such as seizures, migraine, involuntary movements, autonomic
      symptoms, and impaired mental development also improved. Topiramate is worth
      trying when treating patients with AHC as a first trial, or a substitute for
      flunarizine once the latter agent loses effect.

PMID- 17177150
TI  - Attention-deficit hyperactivity disorder and blood mercury level: a case-control
      study in Chinese children.
AB  - OBJECTIVE: To investigate the association between blood mercury level and
      attention-deficit hyperactivity disorder (ADHD) in Chinese children in Hong Kong.
      METHODS: Fifty-two children with ADHD aged below 18 years diagnosed by DSM IV
      criteria without perinatal brain insults, mental retardation or neurological
      deficits were recruited from a developmental assessment center. Fifty-nine normal
      controls were recruited from a nearby hospital. Blood mercury levels were
      measured by cold vapor atomic absorption spectrophotometry. RESULTS: The mean
      ages of cases and controls were 7.06 and 7.81 years respectively. Boys
      predominated (case = 44 [84.6 %], control = 44 [74.6 %]). There was significant
      difference in blood mercury levels between cases and controls (geometric mean
      18.2 nmol/L [95 % CI 15.4 - 21.5 nmol/L] vs. 11.6 nmol/L [95 % CI 9.9 - 13.7
      nmol/L], p < 0.001), which persists after adjustment for age, gender and parental
      occupational status (p < 0.001). The geometric mean blood mercury level was also
      significantly higher in children with inattentive (19.4 nmol/L, 95 % CI 13.3 -
      28.5 nmol/L) and combined (18.0 nmol/L, 95 % CI 14.9 - 21.8 nmol/L) subtypes of
      ADHD. Blood mercury levels were above 29 nmol/L in 17 (26.9 %) cases and 6 (10.2
      %) controls. Children with blood mercury level above 29 nmol/L had 9.69 times (95
      % CI 2.57 - 36.5) higher risk of having ADHD after adjustment for confounding
      variables. CONCLUSION: High blood mercury level was associated with ADHD. Whether
      the relationship is causal requires further studies.

PMID- 17177151
TI  - Proton MR spectroscopic imaging in ataxia-telangiectasia.
AB  - OBJECT: Ataxia-telangiectasia (A-T) is a recessively inherited neurodegenerative
      disorder with prominent progressive ataxia and cerebellar degeneration, as well
      as manifest abnormalities of tone, posture, and movement suggesting
      extrapyramidal dysfunction. In this study, we tested the hypothesis that regional
      metabolite levels, as measured by proton magnetic resonance spectroscopic
      imaging, would be abnormal in patients with A-T in the posterior fossa and basal
      ganglia, reflecting the underlying neurodegenerative processes in these regions.
      METHODS: Spectroscopic images of N-acetyl aspartate (NAA), choline (Cho), and
      creatine (Cr) were obtained in 8 patients with A-T and 8 age-matched controls.
      Normalized metabolite levels were compared between A-T patients and control
      subjects in various regions of interest, including the cerebellum, brainstem, and
      basal ganglia. RESULTS: A-T patients were distinguished from controls by the
      profound loss of all metabolites in the cerebellar vermis (NAA, p < 0.01; Cr and
      Cho, p < 0.05) and a trend for decreased metabolites within the cerebellar
      hemispheres. No abnormalities were detected in the basal ganglia. CONCLUSIONS:
      Proton MR spectroscopic features in A-T closely correlate with the morphologic
      neuroimaging findings of posterior fossa atrophy. Although symptoms suggesting
      extrapyramidal dysfunction are part of the A-T phenotype, these are not
      associated with altered metabolite levels in the basal ganglia.

PMID- 17177152
TI  - Neurological examination at 6 to 9 months in infants with cystic periventricular
      leukomalacia.
AB  - The Hammersmith Infant Neurological Examination was performed in 24 infants with
      cystic periventricular leukomalacia whose gestational age ranged between 26-38
      weeks. The infants were examined between 6 and 9.5 months corrected age. The aim
      of the study was to establish the different patterns of neurological abnormality
      as well as the optimality scores that predict the severity of motor sequelae at 2
      years. Increased neck and trunk extensor tone, and a posture of flexed arms and
      extended legs between 6 and 9 months were always associated with the inability to
      sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs
      were associated with unsupported sitting but not walking. Optimality scores
      between 41 and 60 were generally associated with sitting but not walking at 2
      years whilst scores below 40 were always associated with the inability to sit
      independently at 2 years. All infants who did not develop cerebral palsy at 2
      years had scores > 60. Our results suggest that the pattern of findings on
      neurological examination performed between 6 and 9 months as well as the
      calculated optimality score helps to predict motor impairment in infants with
      PVL.

PMID- 17177153
TI  - Rapidly progressive vanishing white matter disease in a child with previously
      inconspicuous brain MRI.
AB  - In this pediatric case of vanishing white matter disease with early onset,
      rapidly progressive course, and fatal outcome, the white matter vanishing process
      in patient was for the first time documented morphologically in detail: An
      initial magnetic resonance imaging documented a normal appearing brain
      maturation. Rapid progressive brain lesions initiated morphologically DE NOVO in
      the former well myelinated deep white matter were observed six months later after
      disease onset, including concentric ongoing signs of restricted proton diffusion
      cytotoxic edema on diffusion weighted imaging. Cyst-like defects at the lesion
      center of the deep white matter were detected more clearly on MRI ten months
      later. A pathomechanism like tumor necrosis factor induced oligodendrocyte
      apoptosis and primary demyelination was postulated. The case demonstrates that in
      the presence of clinically progressive symptoms, the development of VWM is
      possible even if first MRI findings are negative.

PMID- 17177154
TI  - Treatment of early onset multiple sclerosis with suboptimal dose of interferon
      beta-1a.
AB  - BACKGROUND: Patients with early onset multiple sclerosis may develop disability
      at a younger age than adults. There are several reports about safety of beta
      interferons in childhood and juvenile MS with different doses. OBJECTIVES: To
      determine safety and efficacy of substandard dose of intramuscular interferon
      beta-1a in a prospective randomized trial in patients with multiple sclerosis
      under the age of 16. METHODS: Sixteen patients were divided into two groups
      randomly. The first group was treated with intramuscular interferon beta-1a 15
      micrograms once a week and the second group received no disease-modifying
      therapy. RESULTS: The patients were followed for four years. There was no
      significant side effect and none of the treated patients discontinued the drug.
      There were significant differences between two groups regarding relapse rates (p
      = 0.04), disability progression (p = 0.01), and new T2 lesions (p = 0.006).
      CONCLUSION: Treatment with interferon beta-1a is well tolerated for a long period
      of time and may be effective in substandard doses in early onset multiple
      sclerosis.

PMID- 17177155
TI  - The mildest form of acute necrotizing encephalopathy associated with influenza A.
AB  - We experienced the mildest form of acute necrotizing encephalopathy associated
      with influenza A. A previously healthy 13-year-old girl had mildly decreased
      consciousness and delirious behavior lasting for a week. Diffusion-weighted
      imaging showed mildly high signal intensities in the bilateral thalami, deep
      white matter in the centrum semiovale, and frontal lobes. Conventional T (1)- or
      T (2)-weighted images revealed no abnormalities.

PMID- 17177156
TI  - Human kallikrein 3 (prostate specific antigen) and human kallikrein 5 expression
      in salivary gland tumors.
AB  - The human kallikrein 5 protein (hK5) is expressed in many normal tissues, most
      notably in skin, breast, salivary gland and esophagus. It has also been shown to
      be a potential biomarker for breast, ovarian and testicular cancer. Human
      kallikrein 3 (hK3; prostate-specific antigen) is the most useful marker for
      adenocarcinoma of the prostate gland. The aim of this study was to determine
      whether hK3 and hK5 are expressed in salivary gland tissues and salivary gland
      tumors (both benign and malignant), in order to compare normal with tumor
      tissues. Pleomorphic adenomas, adenoid cystic carcinomas, polymorphous low-grade
      adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas and
      adenocarcinomas not otherwise specified of both minor and major salivary glands
      were examined. The results of this study indicate that most salivary gland tumors
      do not show high levels of expression of hK5. Staining was most prominent in
      keratinizing epithelia in pleomorphic adenomas. hK3 is not expressed in salivary
      gland tumors.

PMID- 17177157
TI  - The effect of venous thromboembolism on survival of cancer patients and its
      relationship with serum levels of factor VIII and vascular endothelial growth
      factor: a prospective matched-paired study.
AB  - BACKGROUND: Venous thromboembolism (VT) increases mortality and morbidity in
      cancer patients. The primary aim of this study was to evaluate the effect of VT
      on the survival of cancer patients and its relationship with serum vascular
      endothelial growth factor (VEGF) and plasma factor VIII levels. PATIENTS AND
      METHODS: Eighty-two patients with locally advanced or metastatic cancer were
      included in this study between September 2001 and March 2004, and 31 of them had
      VT. Fifty-one matched-paired cancer patients without VT were prospectively
      selected as a control group in the same period. Criteria for the selection of
      control group patients were having the same malignancy, stage, metastatic site,
      performance status and age (+/-5 years) as patients in the VT group. RESULTS:
      Plasma factor VIII and serum D-dimer levels in the VT group were significantly
      higher than those in the control group (p=0.030 and p=0.016, respectively).
      However, mean serum VEGF levels were similar in both groups (p=0.199). In the VT
      group, the median survival of patients who had higher serum VEGF levels (>150
      pg/mL) was significantly shorter than that of patients in the same group with
      lower serum VEGF levels (p=0.005). The median survival of the VT group was 14
      months, whereas it was 25 months in the control group (p=0.199). CONCLUSION:
      There was a worse prognostic trend for cancer patients with VT. Nevertheless, the
      difference in survival was not statistically significant between the groups.
      Plasma factor VIII and serum D-dimer levels might have prognostic value in cancer
      patients with VT. Cancer patients with VT and higher serum VEGF levels had a
      significantly poorer prognosis.

PMID- 17177158
TI  - Rat basophilic leukemia cells (RBL-2H3) generate prostaglandin D2 (PGD2) after
      regulated upon activation, normal T-cell expressed and secreted (RANTES)
      activation.
AB  - Increasing evidence indicates that local neurogenic inflammation, possibly in
      response to different stimuli, may be involved in sensory nerve sensitization,
      migraine generation and some other precipitating events leading to neuronal
      dysfunction in the brain. In addition, mast cells generate eicosanoids that are
      linked to asthma and other inflammatory diseases. Regulated upon activation,
      normal T-cell expressed and secreted (RANTES) is a small protein and a prototype
      member of the CC chemokine-beta subfamily with chemoattractant and inflammatory
      properties. In this study we used the RBL-2H3 cell line to determine whether or
      not these cells generate prostaglandin D2 (PGD2) after treatment with RANTES.
      After 4 hours of incubation, RBL-2H3 cells cultured with RANTES at 20 ng/mL
      released large amounts of PGD2 in a dose-response manner compared to control.
      Moreover, RBL-treated RANTES generated a large quantity of histamine. Our study
      confirms once again the proinflammatory action of RANTES, in this case acting on
      the stimulation of the arachidonic acid cascade product PGD2.

PMID- 17177159
TI  - Evidence for cell adhesion-mediated drug resistance of multiple myeloma cells in
      vivo.
AB  - BACKGROUND/AIMS: Multiple myeloma is an incurable disease and patients eventually
      die of disease progression due to drug resistance. VLA-4 (very late antigen 4),
      VCAM (vascular adhesion molecule), LFA-1 (leukocyte function-associated antigen
      1), and ICAM-1 (intercellular adhesion molecule 1)-mediated adhesion of myeloma
      cells to bone marrow stromal cells induces primary multidrug resistance in vitro.
      Based on these preclinical data we hypothesized that myeloma cells with strong
      adhesion - due to strong expression of adhesion molecules on the cell surface -
      are selected by chemotherapy in patients. To prove this hypothesis we determined
      the expression levels of adhesion molecules in 31 multiple myeloma patients by
      flow cytometry. METHODS: A 3-color stain with CD38, CD138 and antibodies against
      VLA-4, ICAM-1, LFA-1, and VCAM was performed. The patients were either at
      diagnosis (chemo-naive; n=17) or at relapse (pre-treated; n=15). Furthermore, the
      response to the next chemotherapy of chemo-naive patients was correlated with the
      expression levels of adhesion molecules. RESULTS: ICAM-1, VLA-4, and VCAM
      expression was higher in pre-treated patients than in chemo-naive patients and
      the expression levels increased with the number of chemotherapy regimens.
      Primarily multidrug-resistant patients had significantly higher expression levels
      of VLA-4 and ICAM-1 than responders. CONCLUSION: This study suggests that
      multiple myeloma cells expressing high levels of VLA-4 and ICAM-1 are drug
      resistant and that such a subpopulation of cells is selected by chemotherapy.

PMID- 17177160
TI  - Prognostic value of circulating KRAS2 gene mutations in colorectal cancer with
      distant metastases.
AB  - While tissue KRAS2 mutations have been extensively investigated, the role of
      circulating mutant KRAS2 gene in patients with colorectal carcinoma remains
      obscure. The aim of the present study was to explore the prognostic significance
      of circulating KRAS2 gene mutational status in subjects undergoing primary
      treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA
      samples extracted from the serum of 86 patients with colorectal cancer and were
      compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2
      status was compared with other clinicopathological variables (including CEA and
      CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in
      tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of
      them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D
      (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate
      analysis, cancer-related survival was associated with Dukes' stage (p<0.0001),
      CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients
      with serum KRAS2 mutations died of the disease within 24 months of primary
      treatment; cancer-related survival was significantly better in 9 stage D patients
      without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1
      patient (13%) alive after 44 months. Residual disease after surgery was evident
      in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage
      D patients without serum mutations. Serum KRAS2 status may impact substantially
      on the management of stage D colorectal carcinoma, since it appears to cor-relate
      with prognosis in this patient subgroup.

PMID- 17177161
TI  - The possible role of chromogranin A as a prognostic factor in organ-confined
      prostate cancer.
AB  - The clinical significance of neuroendocrine differentiation in patients who have
      undergone surgery for localized prostate cancer is still unclear. The aims of
      this study were to assess the relationship between serum neuroendocrine markers
      and well-known prognostic factors in prostate cancer (pathological staging,
      definitive Gleason score and serum PSA) and to search for correlations between
      serum chromogranin A (CgA) levels and pathological findings. Forty-one
      consecutive patients who had undergone radical retropubic prostatectomy for
      clinically localized prostate cancer were evaluated. Serum PSA, CgA and neuron
      specific enolase were measured immediately before surgery. Twenty-six surgical
      specimens were phenotypically and immunohistochemically evaluated using an
      antibody against CgA. Significant correlations were found between serum CgA,
      pathological staging and Gleason score (p=0.049 and p=0.038, respectively). Serum
      CgA did not correlate with PSA, patient age, or immunohistochemical findings.
      There was a significant correlation between positive immunohistochemical CgA
      staining and Gleason score (p=0.014). An increase in serum CgA levels,
      independent of PSA values, might be the expression of pathologically more
      advanced tumor stage and higher Gleason score; this could help to identify a high
      risk patient group eligible for adjuvant therapy.

PMID- 17177162
TI  - Serum ferritin in colorectal cancer patients and its prognostic evaluation.
AB  - The aim of this study was to investigate the relationship between preoperative
      serum ferritin levels, clinico-pathological parameters and survival analysis of
      patients with colorectal cancer. Ninety-four patients (57 males) with a mean age
      of 65 years (39-87 years) underwent 63 curative and 31 palliative operations.
      Follow-up was at least 5 years. Patients were categorized with normal (30-215
      ng/mL in men and 11-148 ng/mL in women), low, or high serum ferritin levels.
      Prognostic evaluation was undertaken with stratified survival analysis and Cox's
      regression model. Twenty-nine of the patients (30.9%) had raised ferritin levels
      and 14 (14.9%) had low values. Comparisons of the survival curves showed
      significant differences in stage C disease; specifically, patients with either
      low or high ferritin levels had a shorter survival than patients with normal
      levels. Patients who underwent palliative surgery and had high ferritin serum
      values also had a shorter survival. In multivariate analysis, the variables with
      a negative effect on survival were stage, serum ferritin levels and age. Our data
      suggest that patients with advanced colorectal cancer having normal preoperative
      serum ferritin levels may have a better prognosis, although the prognostic value
      related to this association requires further investigation.

PMID- 17177163
TI  - Reliability of urinary 6-sulfatoxymelatonin as a biomarker in breast cancer.
AB  - The objective of this study is to evaluate the effect of cryopreservation at
      different storage temperatures on urinary 6-sulfatoxymelatonin (aMT6s)
      concentration. Overnight urine from 28 postmenopausal women participating in the
      ORDET cohort study was filtered and separated into 6 mL aliquots. Urine samples
      were stored at -80 degrees C and at -30 degrees C for an average of 14 years.
      Urinary aMT6s concentration was assessed using a competitive immunoassay. Mean
      aMT6s values of samples stored at -30 degrees C were systematically lower than
      those of samples stored at -80 degrees C (10.7 ng/mL versus 15.8 ng/mL, p<0.001).
      Bland Altman plots showed disagreement between determinations at different
      storage temperatures at the highest levels of the metabolite concentration. The
      degree of agreement evaluated in terms of intraclass correlation coefficient was
      0.68 (95% CI 0.41-0.84, p<0.0001). Pearson's correlation coefficient between
      aMT6s values of the two differently stored samples was 0.93 (p<0.001), while the
      Kendal tau coefficient for rank distribution was 0.73 (p<0.001). Our data suggest
      that storage temperatures might affect degradation of aMT6s during storage.
      However, individual characterization by melatonin levels does not seem to be
      affected by cryopreservation conditions.

PMID- 17177165
TI  - How accurate is intraoperative quick parathyroid hormone measurement in
      establishing complete surgical removal of hyperfunctioning parathyroid tissue?

PMID- 17177164
TI  - Strong association of interleukin-6 -174 G>C promoter polymorphism with increased
      risk of oral cancer.
AB  - In view of the recently found contribution of factors associated with thrombosis
      and inflammation to carcinogenesis, we investigated the possible association of
      interleukin-6 (IL-6) with an increased risk of oral cancer. In DNA samples of 162
      patients with oral squamous cell carcinoma and 156 healthy controls of comparable
      ethnicity, age and sex, we studied the -174 G>C polymorphism in the IL-6 gene,
      which affects its transcription. C allele frequencies were significantly
      increased in patients compared to controls, 42.6% versus 23.1% (p<0.001). The CC
      homozygotes had a 7-fold greater risk of developing oral cancer (odds ratio 7.39,
      95% CI 2.61-20.92), while the GC heterozygotes had a 4-fold greater risk (odds
      ratio 3.74, 95% CI 2.29-6.11). A significant increase in C alleles was observed
      in patients regardless of their smoking or alcohol consumption habits, early or
      advanced stage of cancer, and presence or absence of a family history for cancer
      or thrombophilia (p<0.001; Fisher's exact test). These findings suggest that the 
      174 G>C polymorphism, by affecting IL-6 gene expression, is strongly associated
      with oral oncogenesis.

PMID- 17177166
TI  - Age-period-cohort models for the Lexis diagram.
AB  - Analysis of rates from disease registers are often reported inadequately because
      of too coarse tabulation of data and because of confusion about the mechanics of
      the age-period-cohort model used for analysis. Rates should be considered as
      observations in a Lexis diagram, and tabulation a necessary reduction of data,
      which should be as small as possible, and age, period and cohort should be
      treated as continuous variables. Reporting should include the absolute level of
      the rates as part of the age-effects. This paper gives a guide to analysis of
      rates from a Lexis diagram by the age-period-cohort model. Three aspects are
      considered separately: (1) tabulation of cases and person-years; (2) modelling of
      age, period and cohort effects; and (3) parametrization and reporting of the
      estimated effects. It is argued that most of the confusion in the literature
      comes from failure to make a clear distinction between these three aspects. A set
      of recommendations for the practitioner is given and a package for R that
      implements the recommendations is introduced.

PMID- 17177167
TI  - It might be premature to reject the assumption of a power curve relationship
      between VAS and SG data: three comments on Stevens, McCabe and Brazier's 'Mapping
      between VAS and SG data; results from the UK HUI Index 2 valuation survey'.
AB  - In a recent paper in Health Economics, Stevens, McCabe and Brazier (Health Econ.
      2006; 15: 527-533.) found that the cubic relationship between Visual Analog Scale
      (VAS) values and standard gamble (SG) utilities was superior to other functional
      forms in terms of explanatory power and predictive ability. Consequently, they
      question the reliance on the assumption of a power curve relationship, which was
      established, theoretically and empirically, in earlier works. This note argues
      that: (1) SMB's conclusions are incorrect. The estimated cubic function overfits
      the four data points, and is questionable with respect to the implied attitude
      toward relative risk. (2) The evaluation of the functional forms in terms of the
      individual predictions' mean absolute error is misleading and (3) correcting for
      heteroscedasticity improves the precision of the estimates and of the
      predictions.

PMID- 17177168
TI  - Methyl tert-butyl ether (MTBE)-induced cytotoxicity and oxidative stress in
      isolated rat spermatogenic cells.
AB  - Methyl tert-butyl ether (MTBE) is a class of synthetic organic chemical. In the
      USA, MTBE pollution is regarded as a serious environmental problem. The objective
      of the present study was to investigate the cytotoxic effects and oxidative
      stress induced by MTBE in isolated rat spermatogenic cells. In cytotoxic
      experiments, spermatogenic cells isolated from the testes of adult Sprague-Dawley
      rats by a mechanical procedure without the use of trypsin were incubated with
      medium alone (control), 0.5, 5, 50 mm MTBE, respectively, for 6, 12 and 18 h. MTT
      assay, staining with fluorescein diacetate (FDA) and propidium iodide (PI) and
      flow cytometric analyses were used. In oxidative stress experiments, the
      spermatogenic cells were incubated with medium alone (control) and with 0.5, 50
      microm, 5 mm MTBE. For 1, 2, 6, 12, 18 h incubation, ROS production was tested
      using a 2',7'-dichlorofluorescein diacetate (DCHF-DA) probe; for 1, 3, 6, 12, 18
      h incubation, cytosolic superoxide dismutase (SOD) and extracellular SOD
      (SOD(EX)) activity was assessed; and for 18 h incubation, lipid peroxidation was
      assessed. The results showed that MTBE at high doses significantly decreased the
      spermatogenic cell viability and increased plasma membrane damage and the ratio
      of necrotic cells compared with the control. Assessment of the MTBE-induced
      oxidative stress revealed that MTBE increased the production of reactive oxygen
      species (ROS) and enhanced lipid peroxidation. In addition, although SOD(EX)
      activity increased at a high dose level, cytosolic SOD activity decreased. These
      results suggest that an increase of MTBE-induced ROS production and an
      enhancement of membrane lipid peroxidation may play an important role in its
      cytotoxicity in isolated rat spermatogenic cells.

PMID- 17177169
TI  - High-performance liquid chromatography coupled with electrospray ionization
      tandem mass spectrometry for the determination of flocoumafen and brodifacoum in
      whole blood.
AB  - A high-performance liquid chromatographic-tandem mass spectrometric (HPLC-MS-MS)
      assay was developed and validated to determine quantitatively flocoumafen and
      brodifacoum in whole blood using warfarin as an internal standard (IS). Liquid
      liquid extraction, using ethyl acetate, was used to isolate flocoumafen,
      brodifacoum and the IS from the biological matrix. Detection was performed on a
      mass spectrometer by negative electrospray ionization (ESI) in multiple reaction
      monitoring (MRM) mode. The calibration curves were linear (r(2) > 0.998) in the
      concentration range of 0.1-100.0 ng ml(-1) with a lower limit of quantification
      of 0.05 ng ml(-1) for flocoumafen, and 0.1 ng ml(-1) for brodifacoum in whole
      blood. Intra-day and inter-day relative standard deviations (RSDs) were less than
      8.0% and 10.8%, respectively. Recoveries of flocoumafen and brodifacoum ranged
      from 78.0% to 83.7%. This assay can be used to determine trace flocoumafen and
      brodifacoum in whole blood to investigate suspected poisoning of human and
      animals.

PMID- 17177170
TI  - Boosting silica levels in wheat leaves reduces grazing by rabbits.
AB  - Systemic application of sodium silicate can significantly enhance the levels of
      leaf silica in winter wheat (Triticum aestivum L. cv. Mercia), suggesting that
      this material could reduce the palatability of plants to vertebrate herbivores
      (e.g. rabbits, Oryctolagus cuniculus L.). A bioassay was developed using
      hydroponically grown wheat plants. Plants treated with sodium silicate were
      significantly more resistant to grazing by wild rabbits than untreated plants,
      with severe, potentially lethal feeding damage being reduced by over 50%. Further
      studies were carried out to develop more practical techniques for boosting silica
      levels in plants using silicon-rich 'fertilisers' including calcium silicate and
      calcium silicate slag (CSS). Silica levels were elevated in the plant 1.9-2.8
      times over the control through the application of various silicon materials, in
      line with those of the hydroponic treatment. Encouragingly, levels of silica were
      elevated even in young wheat plants, which are most vulnerable to rabbit damage,
      and in a range of wheat varieties. The use of CSS is particularly promising
      because of its lower cost in comparison with calcium silicate, and it has a
      proven track record in slag fertilisation of rice and sugar cane crops. At the
      optimum CSS application rate of 3 g silicon L(-1) soil, wheat silica levels were
      approximately doubled, with no detrimental impacts on long-term growth or yield.

PMID- 17177171
TI  - Study of UV-shielding properties of novel porous hollow silica nanoparticle
      carriers for avermectin.
AB  - The shielding protection given by self-prepared porous hollow silica
      nanoparticles (PHSN) to pesticides from degradation by UV light was investigated
      using avermectin as a model pesticide. It was demonstrated that PHSN carriers
      with a shell thickness of approximately 15 nm and a pore diameter of 4-5 nm have
      an encapsulation capacity of 625 g kg(-1) for avermectin using a supercritical
      fluid loading method. PHSN carriers exhibited remarkable UV-shielding properties
      for avermectin. This was affected by the intensity of UV light, the pH and the
      temperature of the release medium. Rises in UV intensity, pH and/or temperature
      reduced the UV protection of PHSN for avermectin. In addition, avermectin loaded
      into the inner core of the PHSN carriers was released slowly into the release
      medium for about 30 days following a typical sustained-release pattern. It thus
      appears that PHSN carriers have a promising future in applications requiring
      sustained pesticide release.

PMID- 17177173
TI  - Developmental toxic effects of ethylbenzene or toluene alone and in combination
      with butyl acetate in rats after inhalation exposure.
AB  - First, the developmental toxic potential of n-butyl acetate (BA) was examined in
      Sprague-Dawley rats following whole body inhalation exposure, 6 h day(-1), from
      day 6 to 20 of gestation, at concentrations of 0, 500, 1000, 2000 and 3000 ppm.
      Maternal toxicity was evidenced by significant decreases in body weight gain at
      2000 and 3000 ppm, and by reduced food consumption at 1000 ppm and higher
      concentrations. The effects on prenatal development were limited to a significant
      decrease in fetal weight at 3000 ppm. Thus, inhaled BA was not a selective
      developmental toxicant. In the second part of this study, the developmental toxic
      effects of simultaneous exposures to ethylbenzene (EB) and BA, or to toluene
      (TOL) and BA were evaluated. Pregnant rats were administered EB (0, 250 or 1000
      ppm) and BA (0, 500 or 1500 ppm), or TOL (0, 500 or 1500 ppm) and BA (0, 500,
      1500 ppm), separately and in combinations, using a 2 x 2 factorial design. The
      maternal weight gain was reduced after exposure to 1000 ppm EB, to 1500 ppm BA,
      or to 1500 ppm TOL, either alone or in binary combinations. A significant
      reduction of fetal weight was associated with exposure to 1000 ppm EB alone, to
      either mixtures of EB with BA, or to 1500 ppm TOL alone or combined with BA at
      either concentration. No embryolethal or teratogenic effects were observed
      whatever the exposure. There was no evidence of interaction between EB and BA or
      between TOL and BA in causing maternal or developmental effects.

PMID- 17177172
TI  - Comparative effects of dimethylsulfoxide on metabolism and toxicity of carbon
      tetrachloride and dichloromethane.
AB  - The effects of dimethylsulfoxide (DMSO) on the metabolism and toxicity of
      chlorinated methanes were examined. Male mice were treated with DMSO (1, 2.5 or 5
      ml kg(-1), i.p.) prior to challenge with dichloromethane (CH(2)Cl(2)) or carbon
      tetrachloride (CCl(4)). Blood carboxyhemoglobin elevation resulting from
      metabolic conversion of CH(2)Cl(2) to carbon monoxide was inhibited dose
      dependently by DMSO pretreatment. The elevation of serum aspartate
      aminotransferase, alanine aminotransferase and sorbitol dehydrogenase activities
      induced by CCl(4) (0.1 mmol kg(-1)) was not changed in mice pretreated with DMSO
      at 1 ml kg(-1), but depressed significantly at a greater dose of DMSO. However,
      DMSO failed to alter the hepatotoxicity of CCl(4) injected at a dose of 0.2 mmol
      kg(-1). DMSO induced the microsomal p-nitrophenol hydroxylase and p-nitroanisole
      O-demethylase activities as early as 2 h following the treatment. Microsomal
      disposition of CH(2)Cl(2) and CCl(4) was measured using a vial equilibration
      technique. The disappearance of CH(2)Cl(2) was inhibited competitively by
      addition of DMSO. But DMSO did not affect the metabolic degradation of CCl(4).
      The results indicate that DMSO has multiple effects on metabolism and toxicity of
      xenobiotics. DMSO induces the hepatic metabolizing activity mediated by CYP2E1,
      but the presence of this solvent in the enzyme site may inhibit directly the
      enzymatic interaction with a substrate. The toxicological significance of DMSO
      induced effects on such an interaction may be variable depending on the
      properties of each substrate. The invulnerability of CCl(4) metabolism to the
      effects of DMSO appears to be related to its high affinity for the lipophilic CYP
      enzyme site.

PMID- 17177175
TI  - Relative risk and acceleration in lung cancer.
AB  - For a substance that increases the relative risk of disease, it does not
      necessarily follow that the proportion of cases due to exposure to the substance
      is the same as the attributable fraction in the exposed. An alternative
      explanation is that the substance has accelerated the occurrence of disease and,
      therefore, played a role in all cases. When the incidence of disease with time
      follows the Weibull distribution, it is well known that the proportional hazards
      model and the accelerated failure time model are equivalent. The purpose of this
      paper is to provide a numerical illustration of the relationship between the
      relative risk and the acceleration time of occurrence of cases. A Weibull
      distribution is a good approximation for lung cancer death rates up to the age of
      80 years. The numerical relationship between the relative risk and the time by
      which cases are accelerated is given for lung cancer deaths occurring at ages of
      40-75 years with relative risks of 1.01-3. As an example, for a death due to lung
      cancer at age 60 years in a smoker, relative risks of 2 and 1.1 due to
      occupational exposure to a substance correspond to accelerations of 5.2 years and
      8 months, respectively.

PMID- 17177174
TI  - Interaction of rat renal glucocorticoid receptor with Hsp90 and Hsp70 upon stress
      provoked by mercury.
AB  - The influence of mercury on the association of rat kidney glucocorticoid receptor
      (GR) with heat shock proteins Hsp90 and Hsp70 was investigated. The GR
      heterocomplexes with Hsp90 and Hsp70 were immunopurified from the renal cytosol
      of rats administered different doses of mercury (1, 2 and 3 mg Hg kg(-1) b.w.). A
      quantitative immunoblotting procedure was applied to determine the levels of GR,
      Hsp90 and two nucleocytoplasmic Hsp70 isoforms (constitutive Hsp73 and inducible
      Hsp72) in the renal cytosol, as well as the amounts of these proteins within GR
      heterocomplexes immunoprecipitated by anti-GR antibody. Mercury was found to
      stimulate GR association with all the examined Hsps. The most prominent effect of
      the metal was stimulation of Hsp72 interaction with GR. On the other hand, the
      metal administration led to an increase of Hsp90 level in the cytosol, while the
      cytosolic levels of Hsp70 isoforms remained unaltered. These findings suggest
      that association of Hsps, at least Hsp70, with the GR might be ascribed to
      changes in the affinity of their interaction rather than to changes in the Hsp
      availability in the cytosol. Therefore, GR heterocomplex assembly seems to be a
      controlled process enabling chaperoning and functioning of the GR to be in
      concert with physiological demands.

PMID- 17177176
TI  - Effects of diesel exhaust particles on cytokine production by splenocytes
      stimulated with lipopolysaccharide.
AB  - It was previously shown that pulmonary exposure of mice to diesel exhaust
      particles (DEP) enhances inflammatory conditions induced by allergens or
      bacterial endotoxin (lipopolysaccharide: LPS) via enhanced local expression of
      cytokines. However, resolution of the underlying mechanisms, in which DEP
      exaggerate inflammation, remains uncompleted. Investigation of the actions of DEP
      on mouse-derived mononuclear cells may provide a clue to the mechanisms, because
      mononuclear cells produce and release several types of cytokines. The present
      study elucidated the effects of DEP on mononuclear cell reactions stimulated with
      LPS in vitro. ICR mouse-derived mononuclear cells, isolated from splenocytes, one
      of the secondary lymphoid tissues, were co-cultured with LPS (1 microg ml(-1))
      and DEP (1, 10 or 100 microg ml(-1)). The protein levels of interferon (IFN)
      gamma, interleukin (IL)-2, IL-10, and IL-13 in the culture supernatants were
      measured 72 h after the co-culture. LPS significantly increased the protein
      levels of IFN-gamma, IL-2 and IL-10. In the presence of LPS, DEP decreased the
      protein levels in a concentration-dependent manner with an overall trend, whereas
      DEP (1, 10 microg ml(-1)) moderately elevated the IL-13 level. These results
      suggest that DEP suppress cytokine production from mononuclear cells stimulated
      with LPS and provide a possible hint for DEP facilitation on inflammatory
      conditions, especially related to Th2 response, in vivo.

PMID- 17177177
TI  - Loss of imprinting and cancer.
AB  - Imprinting is defined as the parental allele-specific expression of a very
      limited set of genes (about 50-80). This regulation depends upon an epigenetic
      marking of parental alleles during gametogenesis. Monoallelic expression ensures
      that the levels of the proteins encoded by imprinted genes, important factors of
      embryonic growth, placental growth or adult metabolism, are assured. Without
      precise control of their expression, developmental abnormalities result, as is
      shown by a number of hereditary over-growth syndromes, including Beckwith
      Wiedemann syndrome. The regulation of imprinted genes is largely dependent on
      methylation marks, which are laid down during embryological development of germ
      cells. Once in place, the methylation status of precise chromosomal regions,
      Imprinting Control Regions (ICRs), is read by either of two mechanisms, chromatin
      barrier formation or untranslated RNAs, thereby ensuring that only the maternal
      or paternal allele is expressed. Each imprinted gene is classified as maternal or
      paternal according to the expressed allele. The stability of the marked regions
      in somatic cells is maintained through each cellular replication by a methylation
      enzyme complex containing Dnmt1. Although the major reading mechanisms of
      imprinted status are known, chromatin boundary formation by CTCF and untranslated
      RNAs, the molecules elaborating the initial ICR methylation, are just being
      uncovered. Mis-regulation of imprinted gene expression (loss of imprinting [LOI])
      is seen frequently and precociously in a large variety of human tumours, making
      LOI a potentially valuable tool for both diagnosis and treatment. In fact, LOI is
      presently considered the most abundant and most precocious alteration in cancer.
      The present review proposes a mechanism responsible for LOI, as well as its
      eventual value in tumour diagnosis and prognosis.

PMID- 17177178
TI  - An essential role for CCAAT/enhancer binding protein beta in bleomycin-induced
      pulmonary fibrosis.
AB  - Pulmonary fibrosis is characterized by inflammation, genesis of myofibroblasts,
      and abnormal tissue repair. Despite extensive research, its pathogenesis remains
      incompletely understood. Previously, the transcription factor CCAAT/enhancer
      binding protein beta (C/EBPbeta) was found to be a key regulator of myofibroblast
      differentiation in vitro, and to be involved in the acute phase and inflammatory
      responses. In an attempt to test the role of C/EBPbeta in the development of
      pulmonary fibrosis, experiments using C/EBPbeta null mice and their wild-type
      littermates were conducted. Our findings indicated that, compared to wild-type
      mice, animals deficient in C/EBPbeta showed significantly reduced fibrotic
      lesions and collagen deposition in the lung upon endotracheal injection of
      bleomycin. Further studies on the mechanisms by which C/EBPbeta regulates
      fibrosis indicated that knockout of C/EBPbeta attenuates inflammatory cytokine
      expression in bleomycin-treated mice. The reduced alpha-smooth muscle actin gene
      expression in either isolated lung fibroblasts or lung tissue from bleomycin or
      saline-treated C/EBPbeta deficient mice suggests that C/EBPbeta regulates
      myofibroblast differentiation during fibrosis. Consistent with this finding,
      cells from C/EBPbeta deficient mice exhibited higher proliferative rates than
      those from wild-type mice. These data suggest that C/EBPbeta plays an essential
      role in pulmonary fibrosis and that this role appears to be multifactorial with
      respect to cytokine expression, cell differentiation, and proliferation.

PMID- 17177179
TI  - Familial social support and depression in breast cancer: an exploratory study on
      a Pakistani sample.
AB  - This exploratory study investigated the relationship between familial social
      support and depression in a Pakistani sample of 80 female breast cancer patients,
      and whether the groups of demographic and medical variables differ on the levels
      of familial social support and depression. Familial social support and depression
      were measured by indigenous scales administered in Urdu language and found to be
      significantly inversely correlated. The groups based on age, number of children,
      financial sources of treatment, and disease stage differed significantly on
      familial social support and depression. No significant group differences were
      found on familial social support and depression between the groups of patients
      living in joint and nuclear families, and those who had and had not undergone
      mastectomy. Results are discussed in the respective social and cultural context.

PMID- 17177180
TI  - Assessing unmet supportive care needs in partners of cancer survivors: the
      development and evaluation of the Cancer Survivors' Partners Unmet Needs measure
      (CaSPUN).
AB  - BACKGROUND: Partners of cancer patients typically provide the majority of
      patients' emotional and physical care. Partners may be profoundly affected by the
      cancer and may experience ongoing supportive care needs across the survivorship
      continuum. Research has been restricted by a lack of psychometrically evaluated
      measures and in this study, a self-report measure of partners' needs was
      developed and empirically evaluated. METHODS: Questionnaire items generated from
      a qualitative study were constructed into a 47- item unmet need measure (Cancer
      Survivors' Partners Unmet Needs measure, CaSPUN). The psychometric properties of
      the CaSPUN were evaluated in 212 partners of patients who had been diagnosed with
      cancer 1-11 years earlier and were currently disease-free. RESULTS: The CaSPUN
      was modified to include 35 unmet need items, 6 positive change items and an open
      ended item. The CaSPUN demonstrates a high level of acceptability, internal
      consistency and construct validity, although test-retest reliability was
      moderate. Factor analysis identified five discrete factors: (1) Relationships,
      (2) Information, (3) Partner Issues, (4) Comprehensive Care and (5) Emotional
      Support. CONCLUSIONS: The CaSPUN permits the identification of long-term
      supportive care needs in generic populations of cancer survivors' partners and
      will assist with the formulation of recommendations regarding required supportive
      care services.

PMID- 17177181
TI  - Landmark-based shape analysis of the archaic Homo calvarium from Ceprano (Italy).
AB  - The Ceprano calvarium represents one of the most important sources of information
      about both the dynamics of the earliest hominid dispersal toward Europe and the
      evolution of the genus Homo in the early-to-middle Pleistocene. In this paper,
      the midsagittal vault profile and the 3D frontal bone morphology of Ceprano are
      investigated comparatively, using landmark coordinates and Procrustes
      superimposition. In fact, despite the fact that the skull appears partially
      distorted by diagenetic pressures (thus precluding a comprehensive landmark-based
      analysis), some aspects of the overall morphology are suitable for consideration
      in terms of geometric morphometrics. The midsagittal profile shows an archaic
      shape, comparable with the H. ergaster/erectus range of variation because of the
      fronto-parietal flattening, the development of the supraorbital and nuchal
      structures, and the occurrence of a slightly larger occipital bone. By contrast,
      the frontal bone displays a derived 3D shape that, mostly because of the widening
      of the frontal squama, appears comparable with the Afro-European variation of the
      Middle Pleistocene (i.e., H. heidelbergensis/rhodesiensis). Taking into account
      the unique morphological pattern displayed by Ceprano, its role as a link between
      early Homo and the Middle Pleistocene populations of Europe and Africa is not
      falsified. Thus, when aspects of the Ceprano's morphology are described within
      the analytical framework provided by geometric morphometrics, the relationships
      between Ceprano and the subsequent Afro-European fossil record are emphasized,
      suggesting the occurrence of an ancestral stock of H.
      heidelbergensis/rhodesiensis that is properly represented by the Italian
      specimen.

PMID- 17177182
TI  - Characteristics of hammer stones and anvils used by wild bearded capuchin monkeys
      (Cebus libidinosus) to crack open palm nuts.
AB  - Capuchins living in Boa Vista (Piaui, Brazil) crack open hard palm nuts on hard,
      level surfaces (anvils) using stones (hammers) as percussive tools. This activity
      leaves diagnostic physical remains: distinctive shallow depressions (pits) on the
      surface of the anvil, cracked shells, and stone hammers on the anvil. To initiate
      comparison of percussive stone tool use and interpretation of the artifacts it
      produces across capuchins, chimpanzees, and hominins, we describe a sample of the
      anvils and hammer stones used by capuchin monkeys at our site. Anvils (boulders
      and logs) were located predominantly in the transition zone between the flat open
      woodland and ridges, in locations that offered some overhead coverage, and with a
      tree nearby, but not necessarily near palm trees. Anvils contained shallow,
      hemispherical pits with smooth interiors. Hammers represent a diverse assemblage
      of ancient rocks that are much harder than the prevailing sedimentary rock out of
      which they eroded. Hard stones large enough to serve as hammers were more
      abundant on the anvils than in the surrounding area, indicating that capuchins
      transport them to the anvils. Capuchins use hammers weighing on average more than
      1 kg, a weight that is equivalent to 25-40% of the average body weight for adult
      males and females. Our findings indicate that capuchins select stones to use as
      hammers and transport stones and nuts to anvil sites. Wild capuchins provide a
      new reference point for interpreting early percussive stone tool use in hominins,
      and a point of comparison with chimpanzees cracking nuts.

PMID- 17177183
TI  - Argentine population genetic structure: large variance in Amerindian
      contribution.
AB  - Argentine population genetic structure was examined using a set of 78 ancestry
      informative markers (AIMs) to assess the contributions of European, Amerindian,
      and African ancestry in 94 individuals members of this population. Using the
      Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%,
      the Amerindian contribution was 19.4%, and the African contribution was 2.5%.
      Similar results were found using weighted least mean square method: European,
      80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the
      current results showed very few individuals (four of 94) with greater than 10%
      African admixture. Notably, when individual admixture was examined, the
      Amerindian and European admixture showed a very large variance and individual
      Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine
      subjects. These results indicate that admixture must be considered when clinical
      epidemiology or case control genetic analyses are studied in this population.
      Moreover, the current study provides a set of informative SNPs that can be used
      to ascertain or control for this potentially hidden stratification. In addition,
      the large variance in admixture proportions in individual Argentine subjects
      shown by this study suggests that this population is appropriate for future
      admixture mapping studies.

PMID- 17177185
TI  - Expression of somatic DNA repair genes in human testes.
AB  - Meiosis is the key process for recombination and reduction of the diploid
      chromosome set to a haploid one. Many genes that have been found in yeast or
      mouse models to play a role in meiosis are also important for the repair of DNA
      damage in somatic cells. To study the DNA repair gene transcriptome during male
      germ cell development, we have developed a specialized cDNA microarray with 181
      human genes which are involved in different somatic DNA repair pathways and/or
      cell cycle control and 45 control house-keeping genes. This DNA repair gene chip
      was used to quantify the mRNA expression levels in three human testes samples
      versus a fibroblast RNA pool. Two hundred twenty genes on the chip (including
      house-keeping genes) showed detectable expression levels in adult testes. Sixty
      four DNA repair- and cell cycle-associated genes showed higher expression levels
      in testicular cells than in mitotically dividing fibroblasts and, therefore, are
      likely to be implicated in meiosis. The microarray results of 17 genes with
      increased expression levels were validated with reverse Northern blots or real
      time quantitative RT PCR. Systematic analyses of the meiotic DNA repair gene
      transcriptome may provide new insights into the genetics of male (in)fertility.

PMID- 17177184
TI  - Lower low-density lipoprotein cholesterol levels are associated with Parkinson's
      disease.
AB  - The apolipoprotein E (APOE) epsilon2 allele has been associated with both
      Parkinson's disease (PD) and lower low-density lipoprotein cholesterol (LDL-C).
      We tested the hypothesis that lower LDL-C may be associated with PD. This case
      control study used fasting lipid profiles obtained from 124 PD cases and 112
      controls. The PD cases were recruited from consecutive cases presenting at our
      tertiary Movement Disorder Clinic, and the controls were recruited from the
      spouse populations of the same clinic. Multivariate odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated from unconditional logistic
      regressions, adjusting for age, gender, smoking status, and use of cholesterol
      lowering agents. Lower LDL-C concentrations were associated with a higher
      occurrence of PD. Compared with participants with the highest LDL-C (> or =138
      mg/dL), the OR was 2.2 (95% CI = 0.9-5.1) for participants with LDL-C of 115 to
      137, 3.5 (95% CI = 1.6-8.1) for LDL-C of 93 to 114, and 2.6 (95% CI = 1.1-5.9)
      for LDL-C of < or = 92. Interestingly, use of either cholesterol-lowering drugs,
      or statins alone, was related to lower PD occurrence. Thus, our data provide
      preliminary evidence that low LDL-C may be associated with higher occurrence of
      PD, and/or that statin use may lower PD occurrence, either of which finding
      warrants further investigation.

PMID- 17177186
TI  - Tumor-lymphatic interactions in an activated stromal microenvironment.
AB  - Metastasis to lymph nodes is a common feature of many human tumors and may
      facilitate dissemination to other parts of the body. Peritumoral lymphatics,
      which are located at the periphery of a primary tumor, appear to be anything but
      peripheral for metastasis, as recent studies have highlighted their critical role
      in disseminating tumor cells to local lymph nodes. The metastatic process,
      including lymphangiogenesis, is likely governed by a complex series of
      interactions among tumor cells, endothelial cells, and non-endothelial stromal
      components. Therefore, a detailed understanding of the biology of the tumor
      microenvironment, particularly as it pertains to peritumoral lymphatics near the
      tumor-stromal junction, may someday translate into clinical approaches that
      target metastasis at the invasive front.

PMID- 17177187
TI  - Diffuse large cell B cell lymphoma presenting as a unilateral eye mass.

PMID- 17177189
TI  - Hematologic reference values for African American children and adolescents.
AB  - Anemia is prevalent among African American children. When evaluating pediatric
      patients for anemia, clinicians refer to the normative hematological reference
      values in reference textbooks. These reference values are used in spite of
      evidence that healthy African American people of all ages have average hemoglobin
      concentrations from 0.5 to 0.73 g/dl below those of Whites. In an earlier study,
      using samples from 2,161 healthy African American children from 2 to 18 years
      old, we found a statistically significant difference (P < 0.0001) in the mean
      hemoglobin value for each age group as compared to reference normative mean
      hemoglobin values. Here we present the results of a comparative analysis of the
      data set from our previous study and the data set from the National Health and
      Nutrition Examination Surveys III (NHANES III) 1988-1994. We found no
      statistically significant difference between these data sets with respect to the
      hemoglobin values for any age or sex group, confirming that African American
      children and adolescents have lower mean hemoglobin values than do Whites. Use of
      the reference hemoglobin values presented here will help prevent the misdiagnosis
      of anemia in African American children and thereby minimize unnecessary
      hematological workups and treatment.

PMID- 17177191
TI  - Philadelphia chromosome?

PMID- 17177192
TI  - Immune heparin-induced thrombocytopenia resulting from preceding exposure to
      heparin catheter flushes.
AB  - Immune heparin-induced thrombocytopenia (HIT) is a life-threatening adverse
      effect of heparin. It can result from any type of heparin exposure and by any
      route of administration; however only a few cases are reported after exposures to
      small quantities of heparin from catheter flushes. The major clinical problem
      associated with HIT is thrombosis. Early detection and institution of
      alternative, non-heparin anticoagulation are important. We report a patient with
      HIT associated with use of therapeutic-dose unfractionated heparin in whom immune
      sensitization to heparin was triggered by two 500-unit exposure to UFH associated
      with intravascular catheter flushing for antineoplastic chemotherapy in a patient
      with colon adenocarcinoma.

PMID- 17177190
TI  - Late onset membranous nephropathy complicating donor lymphocyte infusion for
      leukaemia relapse after allogeneic stem cell transplantation.

PMID- 17177193
TI  - Acute Myelogeneous Leukemia (M0/M1) with novel chromosomal abnormality of
      t(14;17) (q32; q11.2).
AB  - Acute Myelogeneous Leukemia (AML) is a heterogeneous disease with respect to
      morphology, immunophenotype, and genetic rearrangements. Multiple recurrent
      chromosomal aberrations have been identified by conventional cytogenetic
      analysis. In this study, we report a case whose clinical features were suggestive
      of AML-M1 subtype with t(14;17) (q32; q11.2) karyotype involving rearrangement of
      chromosomal segments 17q11.2 and 14q32. This is the first report of novel
      chromosomal translocation in this subset of AML and has not yet been reported
      elsewhere. This rearrangement may include certain cancer associated oncogene(s)
      or genes involved in the differentiation like retionic acid receptor alpha
      (RARA), which may confer differentiation blockage and/or proliferation advantage.

PMID- 17177194
TI  - Jean-Luc D'Hautcourt (1954-2005) tribute.

PMID- 17177195
TI  - Thematic workshop on fluorescence compensation settings in multicolor flow
      cytometry.
AB  - In his program of thematic one-day workshops, the French Association of Cytometry
      had organized a workshop dedicated to the fluorescence compensation settings in
      multicolor flow cytometry. This special day was in honor of our past President
      Jean Luc D'Hautcourt who has been involved in the quality of the use of flow
      cytometry in its clinical and research purposes. Review on fluorescence
      phenomena, compensation rules, settings, and few observed confounding situations
      were presented.

PMID- 17177196
TI  - Twenty years of external quality assurance in clinical cell analysis--a tribute
      to Jean-Luc D'Hautcourt.
AB  - External quality assurance (EQA) programs in clinical cell analysis are now a
      consolidated item of laboratory practice. All the flow cytometric testings with
      an impact on clinical decision making have been submitted to regular EQA programs
      during the last 20 years, and this has produced internationally homogeneous
      guidelines, with a remarkable improvement in result reproducibility.Jean-Luc
      D'Hautcourt was a pioneer in this field, and his valuable contributions to flow
      cytometric method standardization and to the dissemination of the educational
      aspects of EQA programs are recognized. The different methodological approaches
      undertaken in the United States and Europe are discussed. The educational role of
      SIHON in the Benelux Countries and of UKNEQAS for Leucocyte Immunophenotyping
      worldwide is emphasized. Accredited and accreditating EQA programs require an
      impressive degree of organization and technical knowledge, so that only major
      international providers can afford such a task nowadays. However, small local
      studies still provide the necessary stimulus to the continuous improvement of the
      scientifical aspects of EQA schemes.

PMID- 17177197
TI  - Kinetic model of a granular sludge SBR: influences on nutrient removal.
AB  - A mathematical model was developed that can be used to describe an aerobic
      granular sludge reactor, fed with a defined influent, capable of simultaneously
      removing COD, nitrogen and phosphate in one sequencing batch reactor (SBR). The
      model described the experimental data from this complex system sufficiently. The
      effect of process parameters on the nutrient removal rates could therefore be
      reliably evaluated. The influence of oxygen concentration, temperature, granule
      diameter, sludge loading rate, and cycle configuration were analyzed. Oxygen
      penetration depth in combination with the position of the autotrophic biomass
      played a crucial role in the conversion rates of the different components and
      thus on overall nutrient removal efficiencies. The ratio between aerobic and
      anoxic volume in the granule strongly determines the N-removal efficiency as it
      was shown by model simulations with varying oxygen concentration, temperature,
      and granule size. The optimum granule diameter for maximum N- and P-removal in
      the standard case operating conditions (DO 2 mg L(-1), 20 degrees C) was found
      between 1.2 and 1.4 mm and the optimum COD loading rate was 1.9 kg COD m(-3) day(
      1). When all ammonia is oxidized, oxygen diffuses to the core of the granule
      inhibiting the denitrification process. In order to optimize the process, anoxic
      phases can be implemented in the SBR-cycle configuration, leading to a more
      efficient overall N-removal. Phosphate removal efficiency mainly depends on the
      sludge age; if the SRT exceeds 30 days not enough biomass is removed from the
      system to keep effluent phosphate concentrations low.

PMID- 17177198
TI  - Structural and functional effects of disease-causing amino acid substitutions
      affecting residues Ala72 and Glu76 of the protein tyrosine phosphatase SHP-2.
AB  - Mutations of the protein tyrosine phosphatase SHP-2 are implicated in human
      diseases, causing Noonan syndrome (NS) and related developmental disorders or
      contributing to leukemogenesis depending on the specific amino acid substitution
      involved. SHP-2 is composed by a catalytic (PTP) and two regulatory (N-SH2 and C
      SH2) domains that bind to signaling partners and control the enzymatic activity
      by limiting the accessibility of the catalytic site. Wild type SHP-2 and four
      disease-associated mutants recurring in hematologic malignancies (Glu76Lys and
      Ala72Val) or causing NS (Glu76Asp and Ala72Ser), with affected residues located
      in the PTP-interacting region of the N-SH2 domain, were analyzed by molecular
      dynamics simulations and in vitro biochemical assays. Simulations demonstrate
      that mutations do not affect significantly the conformation of the N-SH2 domain.
      Rather they destabilize the interaction of this domain with the catalytic site,
      with more evident effects in the two leukemia associated mutants. Consistent with
      this structural evidence, mutants exhibit an increased level of basal phosphatase
      activity in the order Glu76Lys > Ala72Val > Glu76Asp > Ala72Ser > WT. The
      experimental data also show that the mutants with higher basal activity are more
      responsive to an activating phosphopeptide. A thermodynamic analysis demonstrates
      that an increase in the overall phosphopeptide affinity of mutants can be
      explained by a shift in the equilibrium between the inactive and active SHP-2
      structure. These data support the view that an increase in the affinity of SHP-2
      for its binding partners, caused by destabilization of the closed, inactive
      conformation, rather than protein basal activation per se, would represent the
      molecular mechanism, leading to pathogenesis in these mutants.

PMID- 17177199
TI  - Quetiapine adjunct to selective serotonin reuptake inhibitors or venlafaxine in
      patients with major depression, comorbid anxiety, and residual depressive
      symptoms: a randomized, placebo-controlled pilot study.
AB  - This double-blind, placebo-controlled study examined the efficacy and
      tolerability of quetiapine in combination with selective serotonin reuptake
      inhibitors (SSRIs)/venlafaxine in 58 patients with major depressive disorder,
      comorbid anxiety symptoms (HAM-A-14 score > or =14), and residual depressive
      symptoms (HAM-D-17 score > or =18, CGI-S score > or =4). Patients had received an
      SSRI/venlafaxine (at a predefined therapeutic dose) for > or =6 weeks. Overall,
      62% (18/29) of quetiapine- and 55% (16/29) of placebo-treated patients completed
      the study. The mean change in HAM-D and HAM-A total scores from baseline to Week
      8 (primary endpoint) was significantly greater with quetiapine (mean dose 182
      mg/day) than placebo: -11.2 vs. -5.5 (P=.008) and -12.5 vs. -5.9 (P=.002),
      respectively. The onset of quetiapine efficacy (HAM-D/HAM-A/CGI-I) was rapid (by
      Week 1) and continued through to Week 8. Significant differences (P<.05) from
      baseline to Week 8 were observed between groups in 7/17 HAM-D (including feelings
      of guilt, suicide) and 6/14 HAM-A items (including tension, cardiovascular
      symptoms). Response (> or =50% decrease in total score) was higher for quetiapine
      than placebo: HAM-D, 48% vs. 28% (not significant, NS); HAM-A, 62% vs. 28%
      (P=.02). Remission (total score < or =7) was higher for quetiapine than placebo:
      HAM-D, 31% vs. 17% (NS); HAM-A, 41% vs. 17% (NS). CGI-S, CGI-I, and the Global
      Assessment Scale showed that quetiapine was significantly more effective than
      placebo. For quetiapine, adverse events (AEs) were similar to those previously
      observed; sedation/somnolence/lethargy was the most commonly reported. Here
      quetiapine was shown to be effective as augmentation of SSRI/venlafaxine therapy
      in patients with major depression, comorbid anxiety, and residual depressive
      symptoms, with no unexpected tolerability issues. Further studies are warranted.

PMID- 17177200
TI  - Pathologic findings and clinical outcome of patients undergoing retroperitoneal
      lymph node dissection after multiple chemotherapy regimens for metastatic
      testicular germ cell tumors.
AB  - BACKGROUND: Postchemotherapy surgery is an essential component in the management
      of patients with metastatic germ cell tumors (GCT). The authors assessed their
      institutional experience of retroperitoneal lymph node dissection (RPLND) after
      multiple chemotherapy regimens for advanced GCT. METHODS: By analyzing the
      institutional prospective surgical database from 1989 to 2004, 71 patients were
      identified who underwent RPLND after multiple chemotherapy regimens.
      Clinicopathologic and treatment trends were characterized, and predictors of
      disease-specific survival (DSS) were evaluated. RESULTS: The histologic findings
      at RPLND were fibrosis in 36 men (51%), GCT in 20 men (28%), and teratoma in 15
      men (21%). Patients who underwent RPLND from 1989 to 1998 (n = 47), compared with
      patients who underwent RPLND from 1999 to 2004 (n = 24) were more likely to have
      GCT (36% vs 13%; P = .04). Patients who received taxane-containing chemotherapy
      regimens as salvage therapy had lower rates of GCT at RPLND (14% vs 42%; P =
      .01), higher rates of fibrosis (63% vs 39%; P = .04), and similar rates of
      teratoma (31% vs 33%; P = .9). The 5- and 10-year DSS rates were 74% (95%
      confidence interval [95% CI], 62-86%) and 70% (95% CI, 56-84%), respectively.
      Five-year DSS based on worst histology of RPLND and extraretroperitoneal
      specimens was 87% (95% CI, 75-99%) for fibrosis, 87% for teratoma (95% CI, 63
      100%), and 47% for GCT (95% CI, 23-71%; P = .004). On multivariable analysis,
      retroperitoneal mass > or = 5 cm and GCT were predictors of worse DSS (P = .03
      and P = .005, respectively). CONCLUSIONS: Taxane-based salvage chemotherapeutic
      regimens appear to have decreased the rate of GCT at RPLND. The current data
      support RPLND in select patients after salvage chemotherapy, because a
      considerable proportion has teratoma or GCT, and the 10-year DSS rate after
      resection is 70%.

PMID- 17177201
TI  - Celecoxib inhibits meningioma tumor growth in a mouse xenograft model.
AB  - BACKGROUND: Treatments for recurrent meningiomas are limited. We previously
      demonstrated universal expression of COX-2 in meningiomas and dose-dependent
      growth inhibition in vitro with celecoxib, a COX-2 inhibitor. We therefore tested
      the effects of celecoxib on meningioma growth in a mouse xenograft model.
      METHODS: Meningioma cell lines (IOMM-Lee, CH157-MN, WHO grade I primary cultured
      tumor) were transplanted into flanks of nude mice fed mouse chow with celecoxib
      at varying concentrations (0, 500, 1000, 1500 ppm) ad libitum. Tumors were
      measured biweekly and processed for MIB-1, Factor VIII, COX-2, and VEGF, and
      assayed with transferase-mediated dUTP-biotin nick-end labeling (TUNEL). RESULTS:
      Celecoxib reduced growth of mean tumor volume by 66% (P < .05), 25% (P > .05),
      and 65% (P < .05) compared with untreated controls in IOMM-Lee, CH157-MN, and
      benign tumors, respectively. IOMM-Lee tumors removed from celecoxib treatment
      regained a growth rate similar to the control. Blood vessel density decreased and
      apoptotic cells increased in treated flank tumors. Diminished COX-2 expression
      and VEGF were observed in treated IOMM-Lee tumors. Mean plasma celecoxib levels
      were 845, 1540, and 2869 ng/mL, for low-, medium-, and high-dose celecoxib,
      respectively. CONCLUSIONS: Celecoxib inhibits meningioma growth in vivo at plasma
      levels achievable in humans. Celecoxib-treated tumors were less vascular with
      increased apoptosis. IOMM-Lee tumors treated with celecoxib showed decreased COX
      2 and VEGF expression. COX-2 inhibitors may have a role in the treatment of
      recurrent meningiomas.

PMID- 17177203
TI  - Achieving 80% ten-fold cross-validated accuracy for secondary structure
      prediction by large-scale training.
AB  - An integrated system of neural networks, called SPINE, is established and
      optimized for predicting structural properties of proteins. SPINE is applied to
      three-state secondary-structure and residue-solvent-accessibility (RSA)
      prediction in this paper. The integrated neural networks are carefully trained
      with a large dataset of 2640 chains, sequence profiles generated from multiple
      sequence alignment, representative amino acid properties, a slow learning rate,
      overfitting protection, and an optimized sliding-widow size. More than 200,000
      weights in SPINE are optimized by maximizing the accuracy measured by Q(3) (the
      percentage of correctly classified residues). SPINE yields a 10-fold cross
      validated accuracy of 79.5% (80.0% for chains of length between 50 and 300) in
      secondary-structure prediction after one-month (CPU time) training on 22
      processors. An accuracy of 87.5% is achieved for exposed residues (RSA >95%). The
      latter approaches the theoretical upper limit of 88-90% accuracy in assigning
      secondary structures. An accuracy of 73% for three-state solvent-accessibility
      prediction (25%/75% cutoff) and 79.3% for two-state prediction (25% cutoff) is
      also obtained.

PMID- 17177202
TI  - Chronic haloperidol treatment results in a decrease in the expression of
      myelin/oligodendrocyte-related genes in the mouse brain.
AB  - Schizophrenia is a complex psychiatric illness that manifests as a combination of
      positive symptoms, negative symptoms, and cognitive deficits. Antipsychotic
      drugs, such as haloperidol, attenuate dopamine receptor signaling in neurons and
      constitute the frontline treatment for the positive symptoms of schizophrenia.
      However, haloperidol treatment has also been reported to exacerbate preexisting
      negative symptoms/cognitive deficits and the severity of these deficits has been
      correlated with white matter pathology in schizophrenia. Indeed, several studies
      implicate oligodendrocyte function in the pathophysiology of schizophrenia, but
      it is unknown whether these effects are related to drug treatment. It is well
      established that haloperidol alters gene expression in neurons. However, its
      effect on oligodendrocytes is unknown. In this study, we investigate the effects
      of chronic haloperidol treatment on the expression of eight genes known to play
      critical roles in myelin/oligodendrocyte function. We treated male mice with
      haloperidol (2 mg/kg/day) for 30 days and measured gene expression changes by
      using in situ hybridization analysis and quantitative densitometry. Haloperidol
      caused a decrease in the expression of these genes in several white matter
      regions of the mouse CNS. In contrast, clozapine (10 mg/kg/day) had no effect on
      the expression of a subset of these genes. This has important implications for
      both disease pathology and the consideration of treatment options for patients.

PMID- 17177204
TI  - Transformation of an alpha-helix peptide into a beta-hairpin induced by addition
      of a fragment results in creation of a coexisting state.
AB  - Intrinsic rules of determining the tertiary structure of a protein have been
      unknown partly because physicochemical factors that contribute to stabilization
      of a protein structure cannot be represented as a linear combination of local
      interactions. To clarify the rules on the nonlinear term caused by nonlocal
      interaction in a protein, we tried to transform a peptide that has a fully
      helical structure (Target Peptide or TP) into a peptide that has a beta-hairpin
      structure (Designed Peptide or DP) by adding seven residues to the C terminus of
      TP. According to analyses of nuclear magnetic resonance measurements, while the
      beta-hairpin structure is stabilized in some DPs, it is evident that the helical
      structure observed in TP is also persistent and even extended throughout the
      length of the molecule. As a result, we have produced a peptide molecule that
      contains both the alpha-helix and beta-hairpin conformation at an almost equally
      populated level. The helical structures contained in these DPs were more stable
      than the helix in TP, suggesting that stabilizing one conformation does not
      result in destabilizing the other conformation. These DPs can thus be regarded as
      an isolated peptide version of the chameleon sequence, which has the capability
      of changing the secondary structure depending on the context of the surrounding
      environment in a protein structure. The fact that the transformation of one
      secondary structure caused stabilization of both the original and the induced
      structure would shed light on the mechanism of protein folding.

PMID- 17177206
TI  - Role of tumor-derived proinflammatory cytokines GM-CSF, TNF-alpha, and IL-12 in
      the migration and differentiation of antigen-presenting cells in cervical
      carcinoma.
AB  - BACKGROUND: Proinflammatory cytokines are important in modifying the activity,
      differentiation, and migration of antigen-presenting cells and may influence the
      survival of cancer patients. The study assessed whether GM-CSF, TNF-alpha, and IL
      12, produced by cervical cancer cells, are important for the activity,
      differentiation, and migration of antigen-presenting cells. METHODS: In 90
      patients with cervical carcinoma the number of monocytes/tumor-associated
      macrophages (TAM), mature dendritic cells (DC), and Langerhans cells (LHC) was
      determined using immunohistochemistry. An RNA in situ hybridization technique was
      used to measure the expression level of GM-CSF, TNF-alpha, IL-12p35, and IL
      12p40. RESULTS: TAM were detected intraepithelial as well as in the stroma of the
      tumor. LHC were only detected intraepithelial and mature DC only in the tumor
      stroma. The number of TAM correlated positively with the number of mature DC. The
      expression levels of GM-CSF and TNF-alpha correlated positively with the number
      of TAM and DC. TNF-alpha showed a negative correlation with the number of LHC. A
      significant correlation between the expression of functional IL-12 (IL-12p40) and
      stromal TAM was found. The expression of GM-CSF, TNF-alpha, and IL-12p40 did not
      correlate significantly with disease-free survival. However, high IL-12p40
      expression was associated with a favorable cumulative overall survival.
      CONCLUSIONS: The results suggest that GM-CSF as well as TNF-alpha, produced by
      cervical carcinoma cells, may play a role in the differentiation of monocytes
      into mature DC. Furthermore, TNF-alpha may influence the migration of LHC from
      the tumor.

PMID- 17177205
TI  - Chemotherapy response is an important predictor of local recurrence in Ewing
      sarcoma.
AB  - BACKGROUND: Local recurrence in Ewing sarcoma is associated with a poor
      prognosis. The purpose of the study was to determine the factors that predict
      local recurrence after surgical treatment of the primary tumor. METHODS: Between
      1990 and 2001, 64 patients underwent surgical resection of Ewing sarcoma.
      Surgical margins were assessed histologically and radiologically. Response to
      preoperative chemotherapy was determined by detailed specimen mapping. Local
      recurrence-free survival (LRFS) was calculated by Kaplan-Meier analysis.
      Multivariate analysis was performed with the Cox proportional hazards model.
      RESULTS: A number of factors were found to be associated with local recurrence on
      univariate analysis. Patients with a good response to chemotherapy (> or = 90%
      tumor necrosis), had superior LRFS at 5 years (86% vs 51%, P = .015). Central
      site of disease was associated with an increased rate of recurrence. The LRFS at
      5 years was 50% for the chest wall, 74% for pelvic/scapular, and 86% for
      extremity tumors (P = .083). Positive surgical margin was not a strong predictor
      of recurrence (P = .72). A critical analysis of minimal surgical margin based on
      preoperative magnetic resonance imaging (MRI) and computed tomography (CT) scans
      also failed to reveal an association between margin and local recurrence. In
      multivariate analysis, the 2 independent predictors of local recurrence were
      histological response to chemotherapy and central site of disease. CONCLUSION:
      Local recurrence after surgical resection is a complex phenomenon. An important
      predictive factor is the response to chemotherapy. In the current study, this
      seems to have the largest impact. Central site of disease may be a second
      independent predictive factor.

PMID- 17177207
TI  - Variability in human skin permeability in vitro: comparing penetrants with
      different physicochemical properties.
AB  - Appreciating and compensating for the inherent variability associated with
      percutaneous absorption is essential in optimizing (trans)dermal therapy. In this
      study, the variability in human skin permeability associated with model
      penetrants of differing lipophilicity (caffeine (CF), methyl paraben (MP), and
      butyl paraben (BP)) was examined in a standardized intra-laboratory study (Franz
      cell experiments) using epidermal tissue from various donors. Experimentally
      derived permeability coefficients (K(P)) were also compared to that derived from
      two skin permeation models namely, Potts & Guy and Robinson (revised) models in
      order to further validate the Franz diffusion method employed and also elucidate
      the potential permeation pathway(s) employed by the model penetrants. Intra
      subject variability associated with skin permeation of the model penetrants was
      generally found to be lower than inter-subject variability. Experimental K(P)
      values were found to be the same order of magnitude as predicted by the
      mathematical models. Calculated residual variance suggested the Potts and Guy's
      model to be relatively accurate in predicting skin permeability of the two
      parabens whilst the Robinson (revised) model was more effective for CF. The high
      variability in CF permeation compared to the parabens may suggest the in vitro
      skin permeation of solutes becomes more sensitive to intra- and/or inter-subject
      variation in skin lipid content, appendageal density, and imperfections (pores,
      cracks) as the hydrophilic nature of the solute increases. Such variability in
      skin permeability suggests a difference in CF permeation kinetics relative to the
      parabens. As such when performing in vitro drug permeation studies, it is
      essential that the variability in the absorption of the model permeants,
      according to their physicochemical properties, is considered when they are used
      to normalize or standardize any resulting data.

PMID- 17177208
TI  - Neuroprotection of retinal ganglion cells in DBA/2J mice with GDNF-loaded
      biodegradable microspheres.
AB  - This study aims to promote long-term retinal ganglion cell (RGC) survival in a
      spontaneous glaucoma model by injecting slow-release Poly(DL-lactide-co
      glycolide) (PLGA) microspheres containing glial cell line-derived neurotrophic
      factor (GDNF) into the vitreous. Microspheres (1 microL) suspended in PBS were
      injected in ipsilateral eyes while contralateral eyes served as untreated
      controls. Mice were injected at 2 months intervals (1-4 injections) depending on
      the protocol. ELISA assay indicated a cumulative GDNF release of 35.4 ng/mg over
      71 days. The release was nonlinear with an initial burst of over 50%. Mice
      displayed a 30% drop in RGC density by 8 months (p = 0.013) and 80% drop by 10
      months (p < 0.01). GDNF delivery increased RGC survival in all groups. Mice
      receiving early treatment showed up to 3.5 times greater RGC density than
      untreated mice at 15 months survival (p < 0.05). No significant effect was found
      in sham or lens injury groups. Microsphere-delivered GDNF significantly increases
      long-term RGC survival in a spontaneous glaucoma model, although the nonlinear
      release kinetics suggest that burst release may play a role in this rescue.
      Neuroprotection with slow-release polymers with improved release kinetics should
      be further studied as a potential therapy for glaucoma and other diseases
      involving the loss of central nervous system neurons.

PMID- 17177209
TI  - Antigenotoxic activities of crude extracts from Acacia salicina leaves.
AB  - For centuries, plants have been used in traditional medicines and there has been
      recent interest in the chemopreventive properties of compounds derived from
      plants. In the present study, we investigated the effects of extracts of Acacia
      salicina leaves on the genotoxicity of benzo[a]pyrene (B(a)P) and nifuroxazide in
      the SOS Chromotest. Aqueous, total oligomers flavonoids (TOF)-enriched, petroleum
      ether, chloroform, ethyl acetate, and methanol extracts were prepared from
      powdered Acacia leaves, and characterized qualitatively for the presence of
      tannins, flavonoids, and sterols. All the extracts significantly decreased the
      genotoxicity induced by 1 microg B(a)P (+S9) and 10 microg nifuroxazide (-S9).
      The TOF-enriched and methanol extracts decreased the SOS response induced by
      B(a)P to a greater extent, whereas the TOF-enriched and the ethyl acetate
      extracts exhibited increased activity against the SOS response produced by
      nifuroxazide. In addition, the aqueous, ethyl acetate, and methanol extracts
      showed increased activity in scavenging the 1,1-diphenyl- 2-picrylhydrazyl (DPPH)
      free radical, while 100-300 microg/ml of all the test extracts were active in
      inhibiting O2-production in a xanthine/xanthine oxidase system. In contrast, only
      the petroleum ether extract was effective at inhibiting nitroblue tetrazolium
      reduction by the superoxide radical in a nonenzymatic O2- -generating system. The
      present study indicates that extracts of A. salicina leaves are a significant
      source of compounds with antigenotoxic and antioxidant activity (most likely
      phenolic compounds and sterols), and thus may be useful for chemoprevention.

PMID- 17177210
TI  - Effect of vanillin on toxicant-induced lethality in the Drosophila melanogaster
      DNA repair test.
AB  - Vanillin (VA) modulates the genotoxicity of chemical and physical agents in a
      complex manner. Previous studies indicate that VA inhibits the mutagenicity but
      increases the mitotic homologous recombination caused by at least some genotoxic
      agents. In the present study, we have evaluated the effects of VA on the repair
      of lethal damage produced by three genotoxins, N-ethyl-N-nitrosourea (ENU), ethyl
      methanesulfonate (EMS), and mitomycin C (MMC), using the DNA repair test (DRT) in
      Drosophila melanogaster. VA, 0.25% and 0.5% (w/v), increased the toxicity of MMC
      and EMS in repair-deficient flies, as measured by a decrease in the proportion of
      male to female progeny in the DRT; sex ratios decreased from 18-48% for MMC and
      21-97% for EMS. These effects may be caused by the inhibition of nonhomologous
      DNA end joining caused by VA. In contrast to the results with MMC and EMS, VA
      protected against the lethality of ENU in repair-defective flies, as measured by
      a 43-207% increase in the survival of male flies in the DRT. It was inferred that
      the protective effect was due to VA modulating stages prior to the induction of
      ENU lesions in DNA, including modulating the antioxidant properties of VA and/or
      to its interference with the metabolic activation and/or detoxification of
      specific genotoxins. The results from this study indicate that the
      characterization of VA as a promising agent for preventing damage to genes and
      chromosomes should be tempered by observations that VA can increase the toxicity
      of chemical agents.

PMID- 17177213
TI  - Experimental and theoretical investigations on the catalytic hydrosilylation of
      carbon dioxide with ruthenium nitrile complexes.
AB  - Ruthenium complexes, mer-[RuX(3)(MeCN)(3)] and cis/trans-[RuX(2)(MeCN)(4)] with
      X=Br, Cl, were investigated as precatalysts in homogeneously catalyzed
      hydrosilylation of CO(2). The oxidation state of ruthenium and nature of the
      halide in the precatalysts were found to influence the catalytic activity in the
      conversion of Me(2)PhSiH to the formoxysilane Me(2)PhSiOCHO, with Ru(III) having
      chloride ligands being most active. Monitoring the reactions by in-situ IR
      spectroscopy in MeCN as the solvent indicates an interaction of the precatalyst
      with the silane prior to activation of CO(2). In the absence of CO(2),
      hydrosilylation of the MeCN solvent occurs. Catalytic activity in CO(2)
      hydrosilylation is enhanced by Me(2)PhSiCl, generated during reduction of Ru(III)
      in mer-[RuX(3)(MeCN)(3)] to Ru(II) or, when added as promoter to Ru(II)
      precatalysts. The reaction mechanism for the catalytic cycle has been calculated
      by DFT methods for the reaction of Me(3)SiH. The key steps are: Transfer of the
      Me(3)Si moiety to a coordinated halide ligand, resulting in an L(n)RuH(XSiMe(3))
      intermediate --> CO(2) coordination --> Me(3)Si transfer to CO(2) --> reductive
      elimination of formoxysilane product. This reaction sequence is more favorable
      energetically for chloride complexes than for the analogous bromide complexes,
      which accounts for their differences in catalytic activity. Calculations also
      explain the rate increase observed experimentally in the presence of Me(2)PhSiCl.
      A parallel reaction pathway leads to (Me(3)Si)(2)O as a minor byproduct which
      arises from the condensation of two initially formed Me(3)SiOH molecules.

PMID- 17177212
TI  - The application of ecological momentary assessment to the study of night eating.
AB  - OBJECTIVE: Night eating syndrome (NES) was first described in 1955 by Albert
      Stunkard and colleagues. NES consists of either overeating at night or waking up
      during the night and eating. METHOD: In the current study we used ecological
      momentary assessment (EMA) to describe 14 self-defined night-eaters. The
      participants in the current study completed an EMA protocol of approximately two
      weeks. RESULTS: We found that ratings of hunger appeared to be higher during
      night awakenings than in the evening. Also, both affect and arousal generally
      decreased throughout the day and were lowest during awakening episodes.
      CONCLUSION: The current study adds interesting data in describing the experience
      of night-eating behavior with ecological momentary assessments from self
      described night-eaters.

PMID- 17177214
TI  - Reaction chemistry of complexes containing Pt--H, Pt--SH, or Pt--S fragments:
      from their apparent simplicity to the maze of reactions underlying their
      interconversion.
AB  - The relevance of platinum in the reaction of thiophene and derivatives with
      homogeneous transition-metal complexes as models for hydrodesulfurization has led
      us to the study of the reaction chemistry of complexes containing Pt--H, Pt--SH,
      and Pt--S fragments. Exploration of the reactions triggered by addition of
      controlled amounts of Na2S or NaSH to [Pt2(H)2(mu-H)(dppp)2]ClO4 (1) has provided
      evidence of the formation of complexes [Pt2(mu-H)(mu-S)(dppp)2]ClO4 (2),
      [Pt(H)(SH)(dppp)] (3), [Pt2(mu-S)2(dppp)2] (4), [Pt2(mu-S)(dppp)2] (5) and
      [Pt(SH)2(dppp)], in which dppp denotes 1,3-bis(diphenylphosphanyl)propane.
      Consequently, complexes 1, 2, and 5 as well as the already reported 3, 4, and
      [Pt(SH)2(dppp)] have been obtained and fully characterized spectroscopically.
      Also the crystal structures of 1 and 2 have been solved. Complexes 1-5 constitute
      the main framework of the network of reactions that account for the evolution of
      1 under various experimental conditions as shown in Scheme 1. Apparently, this
      network has complexes 2 and 4 as dead-ends. However, their reciprocal
      interconversion by means of the replacement of one bridging hydride or sulfide
      ligand in the respective {Pt(mu-H)(mu-S)Pt} and {Pt(mu-S)2Pt} cores enables the
      closure of the reaction cycle involving complexes 1-5. Theoretical calculations
      support the existence of the undetected intermediates proposed for conversion
      from 1 to 2 and from 3 to 2 and also account for the fluxional behavior of 1 in
      solution. The intermediates proposed are consistent with the experimental results
      obtained in comparable reactions carried out with labeled reagents, which have
      provided evidence that complex 1 is the source of the hydride ligands in
      complexes 2 and 3. Overall, our results show the strong dependence on the
      experimental conditions for the formation of complexes 1-5 as well as for their
      further conversion in solution.

PMID- 17177211
TI  - Influence of polymorphisms at loci encoding DNA repair proteins on cancer
      susceptibility and G2 chromosomal radiosensitivity.
AB  - Sixteen candidate polymorphisms (13 SNPs and 3 microsatellites) in nine genes
      from four DNA repair pathways were examined in 83 subjects, comprising 23
      survivors of childhood cancer, their 23 partners, and 37 offspring, all of whom
      had previously been studied for G(2) chromosomal radiosensitivity. Genotype at
      the Asp148Glu SNP site in the APEX gene of the base excision repair (BER) pathway
      was associated with childhood cancer in survivors (P = 0.001, significant even
      after multiple test adjustment), due to the enhanced frequency of the APEX Asp148
      allele among survivors in comparison to that of their partners. Analysis of
      variance (ANOVA) of G(2) radiosensitivity in the pooled sample, as well as family
      based association test (FBAT) of the family-wise data, showed sporadic
      suggestions of associations between G(2) radiosensitivity and polymorphisms at
      two sites (the Thr241Met SNP site in the XRCC3 gene of the homologous
      recombinational pathway by ANOVA, and the Ser326Cys site in the hOGG1 gene of the
      BER pathway by FBAT analysis), but neither of these remained significant after
      multiple-test adjustment. This pilot study provides an intriguing indication that
      DNA repair gene polymorphisms may underlie cancer susceptibility and variation in
      radiosensitivity.

PMID- 17177215
TI  - The effect of water on the microstructure of 1-butyl-3-methylimidazolium
      tetrafluoroborate/TX-100/benzene ionic liquid microemulsions.
AB  - The ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4])
      forms nonaqueous microemulsions with benzene with the aid of nonionic surfactant
      TX-100. The phase diagram of the ternary system was prepared, and the
      microstructures of the microemulsion were recognized. On the basis of the phase
      diagram, a series of ionic liquid-in-oil (IL/O) microemulsions were chosen and
      characterized by dynamic light scattering (DLS), which shows a similar swelling
      behavior to typical water-in-oil (W/O) microemulsions. The existence of IL pools
      in the IL/O microemulsion was confirmed by UV/Vis spectroscopic analysis with
      CoCl2 and methylene blue (MB) as the absorption probes. A constant polarity of
      the IL pool is observed, even if small amounts of water are added to the
      microemulsion, thus suggesting that the water molecules are solubilized in the
      polar outer shell of the microemulsion, as confirmed by FTIR spectra. 1H NMR
      spectroscopic analysis shows that these water molecules interact with the
      electronegative oxygen atoms of the oxyethylene (OE) units of TX-100 through
      hydrogen-bonding interactions, and the electronegative oxygen atoms of the water
      molecules attract the electropositive imidazolium rings of [bmim][BF4]. Hence,
      the water molecules are like a glue that stick the IL and OE units more tightly
      together and thus make the microemulsion system more stable. Considering the
      unique solubilization behavior of added water molecules, the IL/O microemulsion
      system may be used as a medium to prepare porous or hollow nanomaterials by
      hydrolysis reactions.

PMID- 17177216
TI  - Silicon-phthalocyanine-cored fullerene dendrimers: synthesis and prolonged charge
      separated states with dendrimer generations.
AB  - Silicon-phthalocyanine-cored fullerodendrimers with up to eight fullerene
      substituents (SiPc-n C(60); n=2, 4, and 8) have been synthesized. Photophysical
      properties of newly synthesized SiPc-n C(60) have been investigated by time
      resolved fluorescence and transient absorption analysis with pulsed laser light.
      Laser photolysis measurements suggest the occurrence of a charge-separation
      process from (1)SiPc* to the C(60) subunits. The nanosecond transient absorption
      spectra in the near-IR region indicate that the lifetimes of the formed radical
      ion pairs are prolonged on the order of SiPc-8 C(60)>SiPc-4 C(60)>SiPc-2 C(60),
      which may be related to the electron migration among the C(60) subunits. The
      usefulness of SiPc-n C(60) as light-harvesting systems, evaluated as a ratio of
      the rates of charge recombination to those of charge separation, increases
      markedly with the dendrimer generation.

PMID- 17177217
TI  - "Spin tweaking" of a high-spin molecule: an Mn25 single-molecule magnet with an
      S=61/2 ground state.

PMID- 17177218
TI  - Massively cooperative adsorbate-induced surface restructuring and nanocluster
      formation.

PMID- 17177219
TI  - Gold(I)-catalyzed annulation of salicylaldehydes and aryl acetylenes as an
      expedient route to isoflavanones.

PMID- 17177220
TI  - Synthesis and electrochemical properties of fullerene-rich nanoclusters
      synthesized by cobalt-catalyzed cyclotrimerization of bis(aryl)alkyne
      fullerodendrimers.

PMID- 17177221
TI  - Preparation of substituted cyclopentadienes through platinum(II)-catalyzed
      cyclization of 1,2,4-trienes.

PMID- 17177222
TI  - Synthesis of palladium icosahedra with twinned structure by blocking oxidative
      etching with citric acid or citrate ions.

PMID- 17177223
TI  - Solvation-controlled luminescence of SmII complexes.

PMID- 17177224
TI  - Quantitative CARS spectroscopy using the maximum entropy method: the main lipid
      phase transition.
AB  - The maximum entropy method for phase retrieval of multiplex coherent anti-Stokes
      Raman scattering (CARS) spectra is described in detail and applied to the time
      resolved measurement of the main lipid phase transition of small, unilamellar 1,2
      dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles subject to a 3 min
      temperature sweep. Since the--thus derived--imaginary part of the third-order
      CARS susceptibility can be directly related to the linear vibrational spectrum,
      the multiplex CARS spectral data can be analyzed quantitatively and without prior
      knowledge of the sample. It is shown that the maximum entropy model provides an
      exact description of the original data, including the noise, if all available
      autocorrelation functions are used. Our findings confirm the acyl-chain order
      disorder phase-transition behavior of small, unilamellar lipid vesicles.

PMID- 17177225
TI  - Exploration of the Ca2+ interaction modes of the nifedipine calcium channel
      antagonist.
AB  - A comprehensive study is carried out using quantum chemical computation and
      molecular dynamics (MD) simulations to gain insight into the interaction between
      Ca(2+) ions and the most important class of calcium channel antagonists-
      nifedipine. First, the chelating structures and energetic characters of
      nifedipine-Ca(2+) in the gas phase are explored, and 25 isomers are found. The
      most favorable chelating mode is a tridentate one, that is, Ca(2+) binds to two
      carbonyl O atoms and one nitryl O atom, where Ca(2+) is above the plane of the
      three O atoms to form a pyramidal structure. Accurate geometric structures,
      relative stabilities, vertical and adiabatic binding energies, and charge
      distributions are discussed. The differences in the geometries and energies among
      these isomers are analyzed from the contributions of chelating sites,
      electrostatics and polarizations, steric repulsions, and charge distributions.
      The interconversions among isomers with similar geometries and energies are also
      investigated because of the importance of the geometric transformation in the
      biological system. Furthermore, certain numbers of water molecules are added to
      the nifedipine-Ca(2+) system to probe the effect of water. A detailed study is
      performed on the hydrated geometries on the basis of the most stable isomer 1.
      Stepwise hydration can weaken the nifedipine-Ca(2+) interaction, and the
      chelating sites of nifedipine are gradually replaced by the added water
      molecules. Hexacoordination is found to be the most favorable geometry no matter
      how many water molecules were added, which can be verified by the MD simulations.
      The transfer of water molecules from the inner shell to the outer shell is also
      supported by MD simulations of the hexahydrated complexes.

PMID- 17177226
TI  - Geometric H/D isotope effects and cooperativity of the hydrogen bonds in
      porphycene.
AB  - We investigate the primary, secondary, and vicinal hydrogen/deuterium (H/D)
      isotope effects on the geometry of the two intramolecular hydrogen bonds in
      porphycene. Multidimensional potential energy surfaces describing the anharmonic
      motion in the vicinity of the trans isomer are calculated for the different
      symmetric (HH/DD) and asymmetric (HD) isotopomers. From the solution of the
      nuclear Schrodinger equation the ground-state wavefunction is obtained, which is
      further used to determine the quantum corrections to the classical equilibrium
      geometries of the hydrogen bonds and thus the geometric isotope effects. In
      particular, it is found that the hydrogen bonds are cooperative, that is, both
      expand simultaneously even in the case of an asymmetric isotopic substitution.
      The theoretical predictions compare favorably with NMR chemical-shift data.

PMID- 17177228
TI  - Thermodynamics of the decomposition processes of donor-acceptor complexes MX3 x
      en x MX3 and MX3 x en.
AB  - The structural and thermodynamic properties of the donor-acceptor (DA) complexes
      of Group 13 metal halides (MX3) with ethylenediamine and their decomposition
      products have been studied theoretically at the B3LYP/LANL2DZ(d,p) level of
      theory. Gas-phase dissociation into various components and HX elimination
      reactions are considered. Both processes are endothermic but favored by entropy.
      Complexes of 2:1 composition are predicted to be stable in the gas phase up to
      640-1000 K. It is found that complexation with the second acceptor molecule
      lowers the HX elimination enthalpy; in turn, HX elimination increases DA bonding
      with a second MX3 molecule. Exceptionally high values of the dissociation
      enthalpies (310-390 kJ mol(-1)) and HX elimination reactions (360-420 kJ mol(-1))
      of the amido compounds MX2NHC2H4NH2 and MX2NHC2H4NHMX2 make them important
      intermediates in the decomposition processes. Dissociation reactions of the
      complexes are more favorable than HX elimination reactions; however, the
      subsequent oligomerization and cyclization processes of coordinationally
      unsaturated amido and imido compounds may facilitate HX elimination. Since HI
      elimination reactions are predicted to be the least endothermic, and aluminum
      containing compounds have the strongest M-N dissociation enthalpies, it is
      expected that compounds based on aluminum iodide are promising objects for
      experimental studies.

PMID- 17177227
TI  - Chiral transformation of achiral J-aggregates of a cyanine dye templated by human
      serum albumin.

PMID- 17177229
TI  - Microscopic evidence of the metalation of a free-base porphyrin monolayer with
      iron.

PMID- 17177230
TI  - Asymmetry of chemical similarity.

PMID- 17177231
TI  - Highlights on the development of A(2A) adenosine receptor agonists and
      antagonists.
AB  - Although significant progress has been made in the past few decades demonstrating
      that adenosine modulates a variety of physiological and pathophysiological
      processes through the interaction with four subtypes of a family of cell-surface
      G-protein-coupled receptors, clinical evaluation of some adenosine receptor
      ligands has been discontinued. Major problems include side effects due to the
      wide distribution of adenosine receptors, low brain penetration (which is
      important for the targeting of CNS diseases), short half-life of compounds, or a
      lack of effects, in some cases perhaps due to receptor desensitization or to low
      receptor density in the targeted tissue. Currently, three A(2A) adenosine
      receptor agonists have begun phase III studies. Two of them are therapeutically
      evaluated as pharmacologic stress agents and the third proved to be effective in
      the treatment of acute spinal cord injury (SCI), while avoiding the adverse
      effects of steroid agents. On the other hand, the great interest in the field of
      A(2A) adenosine receptor antagonists is related to their application in
      neurodegenerative disorders, in particular, Parkinson's disease, and some of them
      are currently in various stages of evaluation. This review presents an update of
      medicinal chemistry and molecular recognition of A(2A) adenosine receptor
      agonists and antagonists, and stresses the strong need for more selective ligands
      at the A(2A) human subtype.

PMID- 17177232
TI  - Synthesis, characterisation, and biological studies of CdTe quantum dot-naproxen
      conjugates.

PMID- 17177233
TI  - Naringin, a grapefruit flavanone, protects V79 cells against the bleomycin
      induced genotoxicity and decline in survival.
AB  - The effect of naringin, a grapefruit flavonone was studied on bleomycin-induced
      genomic damage and alteration in the survival of cultured V79 cells. Exposure of
      V79 cells to bleomycin induced a concentration dependent elevation in the
      frequency of binucleate cells bearing micronuclei (MNBNC) and a maximum number of
      MNBNCs were observed in the cells treated with 50 microg ml(-1) bleomycin, the
      highest concentration evaluated. This genotoxic effect of bleomycin was reflected
      in the cell survival, where a concentration dependent decline was observed in the
      cells treated with different concentrations of bleomycin. Treatment of cells with
      1 mm naringin before exposure to different concentrations of bleomycin arrested
      the bleomycin-induced decline in the cell survival accompanied by a significant
      reduction in the frequency of micronuclei when compared with bleomycin treatment
      alone. The cell survival and micronuclei induction were found to be inversely
      correlated. The repair kinetics of DNA damage induced by bleomycin was evaluated
      by exposing the cells to 10 microg ml(-1) bleomycin using single cell gel
      electrophoresis. Treatment of V79 cells with bleomycin resulted in a continuous
      increase in DNA damage up to 6 h post-bleomycin treatment as evident by migration
      of more DNA into the tails (% tail DNA) of the comets and a subsequent increase
      in olive tail moment (OTM), an index of DNA damage. Treatment of V79 cells with 1
      mm naringin reduced bleomycin-induced DNA damage and accelerated DNA repair as
      indicated by a reduction in % tail DNA and OTM with increasing assessment time. A
      maximum reduction in the DNA damage was observed at 6 h post-bleomycin treatment,
      where it was 5 times lower than bleomycin alone. Our study, which was conducted
      on the basis of antioxidant, free radical scavenging and metal chelating
      properties of naringin demonstrates that naringin reduced the genotoxic effects
      of bleomycin and consequently increased the cell survival and therefore may act
      as a chemoprotective agent in clinical situations.

PMID- 17177234
TI  - Carnosic acid from rosemary extracts: a potential chemoprotective agent against
      aflatoxin B1. An in vitro study.
AB  - Since oxidative stress plays an important role in the toxicity mechanism of
      several mycotoxins such as aflatoxin B1 (AFB1), the use of natural or synthetic
      free radical scavengers could be a potential chemopreventive strategy. Carnosic
      acid (CA) is the major polyphenolic compound present in rosemary plants and it
      can also be found in sage leaves. Its free radical scavenging properties were
      tested with two chemical methods. It was found that it has good free radical
      scavenging capacity at pH 7.4. This study also found that a 24 h pre-treatment
      with 10, 20 and 30 microm CA led to a clear, dose-dependent protective effect on
      cell toxicity, reducing cell death induced by a 24 h exposure with 10 microm
      AFB1, respectively, by 16% (P < 0.05), 26% (P < 0.01) and 63% (P < 0.001). It was
      also found that a 24 h pre-treatment with 20 and 30 microm CA achieved a
      reduction of ROS levels, respectively, of 146% (P < 0.001) and 173% (P < 0.001)
      in HepG2 cells exposed to 10 microm AFB1 for 8 h. Moreover, in cells pre
      incubated with 30 microm CA for 24 h the concentration of 8-OH-deoxyguanine
      decreased by 57% (P < 0.001) with respect to the cells exposed for 24 h to 10
      microm AFB1 alone. The results obtained with the in vitro and chemical studies
      support the theory that AFB1 induced oxidative stress plays an important role in
      the cytotoxic mechanism of this mycotoxin. Furthermore these findings suggest a
      starting point for developing alimentary strategies in order to counteract the
      damage caused by AFB1 contamination in feed and food.

PMID- 17177235
TI  - New approach for rapid detection of known hemoglobin variants using LC-MS/MS
      combined with a peptide database.
AB  - The identification of hemoglobin (Hb) variants is usually performed by means of
      different analytical steps and methodologies. Phenotypic methods, such as gel
      electrophoresis and high performance liquid chromatography, are used to detect
      the different electrophoretic or chromatographic behaviors of hemoglobin variants
      in comparison to HbA0 used as a control. These data often need to be combined
      with mass spectrometry analyses of intact globins and their tryptic peptide
      mixtures. As an alternative to a 'step-by-step' procedure, we have developed a
      'single step' approach for the identification of Hb variants present in
      biological samples. This is based on the microHPLC-ESI-MS/MS analysis of the
      peptide mixture generated by a tryptic digestion of diluted Hb samples and an in
      house new database containing solely the variant tryptic peptide of known human
      Hb variants. The experimental results (full MS and MS/MS spectra) are correlated
      with theoretical mass spectra generated from our in-house-built variant peptide
      database (Hbp) using the SEQUEST algorithm. Simple preparation of samples and an
      automated identification of the variant peptide are the main characteristics of
      this approach, making it an attractive method for the detection of Hb variants at
      the routine clinical level. We have analyzed 16 different samples, each
      containing a different known variant of hemoglobin.

PMID- 17177240
TI  - Study by liquid secondary ion and electrospray mass spectrometry of synthesized
      and formed-in-source metallocorroles.
AB  - Liquid secondary ion and electrospray mass spectrometry were used to study the
      complexation in-source of 5,10,15-tris(pentafluorophenyl)corrole with several
      divalent transition-metal ions. The metallocorrole ions formed in-source were
      identified by comparing their product ion mass spectra with the spectra of the
      same ions formed from metallocorroles obtained from classical procedures.
      Positive metallocorrole ion formation is accompanied by oxidation of the metal
      centre. Mechanisms were proposed for the oxidation processes, and data from
      negative-ion spectra reinforced these mechanisms.

PMID- 17177241
TI  - A proteomic analysis of Psychrobacter articus 273-4 adaptation to low temperature
      and salinity using a 2-D liquid mapping approach.
AB  - Psychrobacter 273-4 was isolated from a 20,000-40,000-year-old Siberian
      permafrost core, which is characterized by low temperature, low water activity,
      and high salinity. To explore how 273-4 survives in the permafrost environment,
      proteins in four 273-4 samples cultured at 4 and 22 degrees C in media with and
      without 5% sodium chloride were profiled and comparatively studied using 2-D HPLC
      and MS. The method used herein involved fractionation via a pH gradient using
      chromatofocusing followed by nonporous silica (NPS) RP-HPLC and on-line
      electrospray mass mapping. It was observed that 33 proteins were involved in the
      adaptation to low temperature in the cells grown in the nonsaline media while
      there were only 14 proteins involved in the saline media. There were 45 proteins
      observed differentially expressed in response to salt at 22 degrees C while there
      were 22 proteins at 4 degrees C. In addition, 5% NaCl and 4 degrees C showed a
      combination effect on protein expression. A total of 56 proteins involved in the
      adaptation to low temperature and salt were identified using MS and database
      searching. The differentially expressed proteins were classified into different
      functional categories where the response of the regulation system to stress
      appears to be very elaborate. The evidence shows that the adaptation of 273-4 is
      based primarily on the control of translation and transcription, the synthesis of
      proteins (chaperones) to facilitate RNA and protein folding, and the regulation
      of metabolic pathways.

PMID- 17177242
TI  - Application of Hadamard transformation to MEKC.
AB  - The Hadamard transform (HT) technique, which permits the S/N in CE to be
      improved, was applied to MEKC. Multiple sample injection of fluorescent analytes
      according to a Hadamard code sequence was performed using an optically gated
      sample injection technique, in which a sample plug was produced based on
      photodegradation by irradiation with an intense laser beam. The capillary and
      reservoirs were filled with a sample solution containing buffer components and
      SDS as a pseudostationary phase. A preliminary study confirmed that fluorescein
      ion could be photobleached in the presence of SDS. The optically gated sample
      injection technique was then applied to multiple sample injection, based on a
      Hadamard matrix. The S/N in the electropherogram obtained by HT-MEKC was improved
      substantially compared to that obtained by a single injection method. When the
      technique was applied to the separation of several amino acids labeled with FITC,
      the S/N ratio for each amino acid was enhanced, without any evidence of
      degradation in separation resolution. Moreover, HT-MEKC was applied to the
      analysis of amino acids contained in a Japanese beverage, resulting in improved
      S/Ns for the amino acids.

PMID- 17177243
TI  - Simultaneous determination of allantoin, hypoxanthine, xanthine, and uric acid in
      serum/plasma by CE.
AB  - Allantoin (All) is an oxidative end product of purines in mammals. The small
      amount of All present in human plasma or serum results from free radical action
      on urate and may provide a stable marker of in vivo free radical activity.
      Because free radicals have been implicated in the development and progression of
      atherosclerosis, this study focused on the metabolic compounds of the All
      pathway. We propose a new fast CE (CE/UV) method for the simultaneous
      determination of All, uric acid (UA), hypoxanthine (HX), and xanthine (X) in
      human plasma. These products were quantified in the plasma of patients with
      chronic renal failure before hemodialysis (n = 6), patients with chronic heart
      failure (n = 6) and controls (n = 6). The filtered plasma were diluted ten-fold
      before the direct injection in CE/UV (195 nm), which allows separating the four
      compounds in less than 13 min. The metabolites were detectable at concentrations
      of 0.3-0.6 micromol/L. The method was linear over the range 0.5-150 micromol/L
      for All, HX, and X and 10-1500 micromol/L for UA (r > 0.99). The analytical
      performance of this method is satisfactory with intra-assay CV < 3.4%, inter
      assay CV < 5% (HX and X < 7%), and recovery (93-101%). The proposed CE-UV method
      appears to be a useful tool for studying physiological and pathological changes
      of HX, UA, and All levels in plasma samples, the latter being a possible
      indicator of free radical damage in vivo.

PMID- 17177244
TI  - Detection of hexamethonium-perchlorate association complexes using NACE-MS.
AB  - Perchlorate (ClO(4) (+)) and other chlorine oxide anions were observed to complex
      weakly with hexamethonium (1,6-bis-(trimethylammonium)-hexane) in both aqueous
      and polar nonaqueous solvents. The resultant positively charged complexes were
      resolved by NACE using 2-propanol/acetone electrolytes prior to mass
      spectrometric detection using an Agilent(3D)CE system coupled to a Bruker Esquire
      3000+ quadrupole IT mass detector. Using electrokinetic injection, the method
      detection limit for perchlorate in nonaqueous media was 10 microg/L. The isotope
      patterns due to the presence of (35)Cl and (37)Cl in complex mass spectra allowed
      for unambiguous identification of perchlorate, chlorate (ClO(3) (+)), chlorite
      (ClO(2) (+)), and chloride (Cl(+)) in photoreaction samples.

PMID- 17177245
TI  - Genetic analysis of human complement factor H polymorphisms.
AB  - Human complement factor H (factor H) is polymorphic, with five previously
      reported FH alleles and three previously reported HF alleles (HF*A, HF*B, and
      HF*Q0). The relationship between the FH and HF alleles is not clear, and the
      genetic basis of factor H phenotypes has not yet been identified. In this study,
      nucleotide sequence analysis of complementary DNA (cDNA) from individuals with
      each HF phenotype identified seven mutated sites in the factor H gene. However,
      in four cases, the same cDNA sequence was observed in individuals with two
      different HF phenotypes. Western blotting and 2-DE also showed that a 160 kDa
      protein corresponding to factor H was expressed in individuals with HF
      phenotypes. In addition, factor H cross-reacting 45 and 42 kDa polypeptides were
      detected in individuals with HF A, HF B, or HF AB phenotypes, but not in
      individuals with the HF Q0 (a null allele) phenotype. Thus, HF phenotype did not
      correlate well with factor H gene or protein structural variation. Evidence is
      provided to support the hypothesis that the HF phenotypes do not correspond to
      polymorphism in factor H, but instead correspond to polymorphism in factor H
      related protein 1. A novel PCR-RFLP method was developed and used to detect four
      polymorphisms (G257A, G1492A, A2089G, and G2881T) in the factor H gene in 54
      unrelated Japanese individuals. This method could be useful for studies on
      genetic disease associated with these mutations.

PMID- 17177246
TI  - Toward an integrated microchip sized 2-D polyacrylamide slab gel electrophoresis
      device for proteomic analysis.
AB  - We describe a miniaturized instrument capable of performing 2-DE. Our
      miniaturized device is able to perform IEF and polyacrylamide slab gel
      electrophoresis (PASGE) in the same unit. It consists of a compartment for a
      first-dimensional IEF gel, which is connected to a second-dimensional PASGE gel.
      The focused samples are automatically transferred from the IEF gel to the PASGE
      gel by electromigration. Our preliminary experiments show that the device is able
      to focus and separate a mixture of proteins in approximately 1 h, excluding the
      time required for the staining procedure. On average, the gel-to-gel retardation
      factor (Rf) variation was 6.2% (+/-0.9%) and pI variation was 2.5% (+/-0.6%).
      Separated protein spots were excised from stained gels, digested with trypsin,
      and further identified by MS, thus enabling direct proteomic analysis of the
      separated proteins.

PMID- 17177247
TI  - Kohlrausch regulating function and other conservation laws in electrophoresis.
AB  - The Kohlrausch regulating function (KRF) is a conservation law (conservation
      function), which is held in electrophoresis and which enables calculation of the
      so-called adjusted concentrations of constituents. The KRF is not the only
      conservation function and, depending on the complexity of the electrophoretic
      system, other conservation laws may be obeyed having a broader range of
      applicability. The conservation laws are tightly related to system
      eigenmobilities and system zones (system peaks). In principle, no system
      eigenmobility is exactly zero, but in most practical cases at least one system's
      eigenmobility is close to zero. The existence of the close-to-zero eigenmobility
      inherently points to the existence of a conservation function and a system zone
      which is stationary. The stationary system zone is called injection zone,
      stagnant zone, water peak, or solvent dip. Electrophoretic (electromigration)
      systems can be divided into two types: (i) conservation systems, in which the
      absolute value of at least one system eigenmobility is close to zero and where at
      least one conservation law is obeyed and (ii) nonconservation systems, where no
      system eigenmobility is close to zero and no conservation law is obeyed. The
      paper reviews work dealing with conservation functions in electromigration,
      derives some "historical" conservation functions in a new way, derives several
      conservation functions for systems of multivalent electrolytes, and discusses
      electrophoretic systems that have nonconservation behavior. In some typical
      instances, the conservation functions are simulated by means of a dynamic
      simulation tool and depicted graphically.

PMID- 17177248
TI  - Molecularly imprinted polymers as a tool for separation in CEC.
AB  - Molecularly imprinted polymers (MIPs) are synthesized in the presence of a
      template which results in the formation of specific recognition cavities
      complementary to the template in shape and chemical functionality. One of the
      most successful application areas of MIPs is chromatographic sorbents, which are
      tailor-made synthetic polymers for a given analyte. However, low efficiency of
      MIP columns is often observed because of slow kinetics of the template. CEC-based
      MIPs are thought to improve efficiency of MIP-based separation due to the
      enhanced flow dynamics of CEC. Another attractive feature is the miniaturized
      format of CEC, so that fewer templates or monomers for the molecular imprinting
      are consumed, a characteristic desired for 'green chemistry'. The small
      dimensions of a capillary demand the development of novel polymer formats that
      can be applied to a miniaturized system. This review discusses the various
      formats, i.e., the micro- or nanoparticle, the coating and the monolith, for
      application in CEC as well as the use in MIP syntheses and characteristics.

PMID- 17177249
TI  - Biospecific interaction (affinity) CEC and affinity nano-LC.
AB  - This review article is aimed at assessing the recent progress made in affinity
      nano-LC and affinity CEC performed in capillaries and microchips. A variety of
      biospecific interactions is covered including lectin affinity, immunoaffinity,
      immobilized metal affinity, sugar-based affinity, protein A affinity, protein G
      affinity, aptamer affinity, enzyme affinity, and other miscellanea. ACE involving
      affinity interaction in free solution is not covered in this review article.
      Also, affinity-based separations involving chiral recognition are not the subject
      of this review article because they are the topic of a more specialized review
      article on chiral separations in this special issue. A total of 31 papers
      published in the period 1998-2006 have been discussed in this review article.

PMID- 17177250
TI  - Fe3+ immobilized metal affinity chromatography with silica monolithic capillary
      column for phosphoproteome analysis.
AB  - Immobilized metal affinity chromatography (IMAC) is a commonly used technique for
      phosphoproteome analysis due to its high affinity for adsorption of
      phosphopeptides. Miniaturization of IMAC column is essential for the analysis of
      a small amount of sample. Nanoscale IMAC column was prepared by chemical
      modification of silica monolith with iminodiacetic acid (IDA) followed by the
      immobilization of Fe3+ ion inside the capillary. It was demonstrated that Fe3+
      IDA silica monolithic IMAC capillary column could specifically capture the
      phosphopeptides from tryptic digest of alpha-casein with analysis by MALDI-TOF
      MS. The silica monolithic IMAC capillary column was manually coupled with
      nanoflow RPLC/nanospray ESI mass spectrometer (muRPLC-nanoESI MS) for
      phosphoproteome analysis. The system was validated by analysis of standard
      phosphoproteins and then it was applied to the analysis of protein
      phosphorylation in mouse liver lysate. Besides MS/MS spectra, MS/MS/MS spectra
      were also collected for neutral loss peak. After database search and manual
      validation with conservative criteria, 29 singly phosphorylated peptides were
      identified by analyzing a tryptic digest of only 12 mug mouse liver lysate. The
      results demonstrated that the silica monolithic IMAC capillary column coupled
      with muRPLC-nanoESI MS was very suitable for the phosphoproteome analysis of
      minute sample.

PMID- 17177251
TI  - Protein labeling by iTRAQ: a new tool for quantitative mass spectrometry in
      proteome research.
AB  - A novel, MS-based approach for the relative quantification of proteins, relying
      on the derivatization of primary amino groups in intact proteins using isobaric
      tag for relative and absolute quantitation (iTRAQ) is presented. Due to the
      isobaric mass design of the iTRAQ reagents, differentially labeled proteins do
      not differ in mass; accordingly, their corresponding proteolytic peptides appear
      as single peaks in MS scans. Because quantitative information is provided by
      isotope-encoded reporter ions that can only be observed in MS/MS spectra, we
      analyzed the fragmentation behavior of ESI and MALDI ions of peptides generated
      from iTRAQ-labeled proteins using a TOF/TOF and/or a QTOF instrument. We observed
      efficient liberation of reporter ions for singly protonated peptides at low
      energy collision conditions. In contrast, increased collision energies were
      required to liberate the iTRAQ label from lysine side chains of doubly charged
      peptides and, thus, to observe reporter ions suitable for relative quantification
      of proteins with high accuracy. We then developed a quantitative strategy that
      comprises labeling of intact proteins by iTRAQ followed by gel electrophoresis
      and peptide MS/MS analyses. As proof of principle, mixtures of five different
      proteins in various concentration ratios were quantified, demonstrating the
      general applicability of the approach presented here to quantitative MS-based
      proteomics.

PMID- 17177252
TI  - Outer membrane proteome of Prevotella intermedia 17: identification of
      thioredoxin and iron-repressible hemin uptake loci.
AB  - Although hemin is an indispensable nutrient for the oral pathogen Prevotella
      intermedia, not much is known regarding the molecular mechanisms of hemin
      acquisition. The availability of the genomic sequence of the bacterium allowed us
      to apply proteomic approaches to identify proteins that may be mediating the
      hemin acquisition process. As hemin acquisition mechanisms have been shown to be
      induced in iron-depleted conditions, we applied proteomic approaches to detect
      those proteins whose expressions were affected by iron. We analyzed 40 protein
      spots and identified 19 such proteins. Interestingly, two proteins drastically
      upregulated in iron-depleted conditions, PIN0009 and PINA0611, are homologs of
      hemin uptake receptors in other bacteria. PIN0009 is predicted to be an outer
      membrane lipoprotein. It is encoded by a gene that is the first of a seven-gene
      genomic locus encoding proteins of a novel hemin acquisition system. The second
      protein, PINA0611, is a homolog of numerous TonB-dependent outer membrane
      receptors including outer membrane iron uptake receptors of various Gram-negative
      bacteria. There was also another protein, regulated by iron, that was previously
      demonstrated to bind hemoglobin in P. intermedia. Finally, we identified a
      thioredoxin-like protein that has a novel outer membrane location.

PMID- 17177254
TI  - Rod and cone input to horizontal cells in the rabbit retina.
AB  - In the rabbit retina, there are two types of horizontal cell (HC). The A-type HC
      is axonless and extensively coupled. The B-type HC is axon bearing; the somatic
      dendrites are radially symmetric and form a second coupled network, while the
      axon branches expansively to form a complex terminal structure. The B-type axon
      terminals (ATs) are independently coupled to form a third network in the outer
      plexiform layer. We have modified our dye-injection methods to obtain detailed
      fills of the three different horizontal cell networks for analysis via confocal
      microscopy. We have confirmed that A-type HCs and the somatic dendrites of B-type
      HCs receive input exclusively from cones, whereas the B-type ATs receive input
      only from rods. A single B-type AT may receive input from as many as 1,000 rods,
      but, surprisingly, our data reveal only one end terminal per rod spherule. The
      somatic dendrites of A- and B-type HCs form clusters at each cone pedicle
      coincident with GluR2/3 and GluR4 glutamate receptor subunits. The B-type ATs
      have GluR2/3- or GluR4-labeled glutamate receptors in two locations: small puncta
      on the end terminals within the rod spherule invagination and large clusters on
      the terminal stalks, approximately 1.5 microm from the rod synaptic ribbon. We
      conclude that AMPA receptors of the same or similar composition mediate
      photoreceptor input to all types of HCs.

PMID- 17177255
TI  - Chemoarchitecture of the middle temporal visual area in the marmoset monkey
      (Callithrix jacchus): laminar distribution of calcium-binding proteins
      (calbindin, parvalbumin) and nonphosphorylated neurofilament.
AB  - We studied the distributions of interneurons containing the calcium-binding
      proteins parvalbumin and calbindin D-28k, as well as that of pyramidal neurons
      containing nonphosphorylated neurofilament (NNF), in the middle temporal visual
      area (MT) of marmoset monkeys. The distributions of these classes of cells in MT
      are distinct from those found in adjacent areas. Similar to the primary visual
      area (V1), in MT, calbindin-immunopositive neurons can be objectively classified
      into "dark" and "light" subtypes based on optical density of stained cell bodies.
      Calbindin-positive dark neurons are particularly concentrated in layers 2 and 3,
      whereas light neurons have a more widespread distribution. In addition, a
      subcategory of calbindin-positive dark neuron, characterized by a "halo" of
      stained processes surrounding the cell body, is found within and around layer 4
      of MT and V1. These cells are rare in most other visual areas. In comparison,
      parvalbumin-immunopositive cells in area MT have a relatively homogeneous
      distribution, although with a trend toward higher spatial density in lower layer
      3, and are relatively uniform in terms of density of staining. Finally, MT shows
      a characteristic trilaminar distribution of NNF-immunopositive pyramidal cells,
      with stained cell bodies evident in layers 3, 5, and 6. Although the laminar
      distribution of cells stained for the three markers overlap to some extent, these
      subcategories can be readily distinguished in terms of morphology, including cell
      body size. Chemoarchitectural parallels observed between MT and V1 suggest
      comparable physiological requirements and neuronal circuitry.

PMID- 17177256
TI  - In vivo imaging of growth cone and filopodial dynamics: evidence for contact
      mediated retraction of filopodia leading to the tiling of sibling processes.
AB  - In the leech embryo, the peripheral comb cell (CC) sends out many nonoverlapping,
      growth cone-tipped processes that grow in parallel and serve as a scaffold for
      the migrating myocytes of the later-developing oblique muscle layer. To explore
      how the parallel arrangement is generated we first examined the arrangement of CC
      cytoskeletal components by expressing a tubulin-binding protein and actin, both
      tagged with fluorescent reporters. This revealed that the growth cones were
      compartmentalized into F-actin-rich filopodia and a microtubule-rich central
      region. Time-lapse analysis with a 2-photon laser scanning microscope revealed
      that the growth cones of the CC are highly dynamic, undergoing rapid filopodial
      extension and retraction. Measurements of filopodial lifespan and length revealed
      that most filopodia at the leading edge of the growth cone achieved significantly
      longer lifespans and length than lateral filopodia. Furthermore, for the short
      lived lateral filopodia, apparent interaction with a neighboring process was
      found to be a significant predictor of their nearly immediate (within 2-4
      minutes) retraction. When contact was experimentally prevented by ablating
      individual CCs, the filopodia from the growth cones of adjacent segmental
      neighbors were found to be significantly lengthened in the direction of the
      removed homolog. Treatment with low doses of cytochalasin D to disrupt F-actin
      assembly led to filopodial retraction and growth cone collapse and resulted in
      the bifurcation of many CC processes, numerous crossover errors, and the loss of
      parallelism. These findings indicate the existence of a contact-mediated
      repulsive interaction between processes of the CC.

PMID- 17177257
TI  - Functional activation of glutamate ionotropic receptors in the developing mouse
      retina.
AB  - Ionotropic glutamate receptors have been associated with early development of the
      visual process by regulating cell differentiation, cell motility, and synaptic
      contacts. We determined the expression of functional ionotropic glutamate
      receptors during development of the mouse retina by assessing 1-amino-4
      guanidobutane (agmatine; AGB) immunolabelling after application of a range of
      glutamate analogs. Colocalization of AGB with calretinin and islet-1 allowed the
      identification of functional receptors in neurochemically defined neurons.
      Activation with kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA), and N-methyl-D-aspartate (NMDA) resulted in AGB entry into neurons
      consistent with that found previous receptor subunit localization studies in the
      developing retina. Temporal analysis revealed that application of 50 microM KA
      activated receptors as early as embryonic day 18 in the ventricular zone and in
      the ganglion cell layer, whereas 30 muM AMPA activated cells predominantly in the
      ganglion cell layer. Cholinergic amacrine cells showed functional KA and AMPA
      receptors upon their insertion into the conventional amacrine cell layer from
      postnatal day 1 (P1). OFF cone bipolar cells showed functional KA receptors from
      P6, at a developmental age when they are known to make contact with ganglion
      cells. NMDA activation led to diffuse AGB labeling at birth among cells in the
      ganglion cell layer, whereas, at P1, regularly spaced cholinergic amacrine cells
      in the conventional amacrine cell layer started to be responsive to NMDA. Non
      NMDA receptors were first to show functional activation in the developing retina,
      and cholinergic amacrine cells displayed functional ionotropic glutamate
      receptors after reaching their final destination.

PMID- 17177258
TI  - Localization and comparative analysis of acid-sensing ion channel (ASIC1, 2, and
      3) mRNA expression in mouse colonic sensory neurons within thoracolumbar dorsal
      root ganglia.
AB  - Reducing colonic mechanosensitivity is an important potential strategy for
      reducing visceral pain. Mice lacking acid-sensing ion channels (ASIC) 1, 2, and 3
      show altered colonic mechanosensory function, implicating ASICs in the
      mechanotransduction process. Deletion of ASICs affects mechanotransduction in
      visceral and cutaneous afferents differently, suggesting differential expression.
      We determined relative expression of ASIC1, 2, and 3 in mouse thoracolumbar
      dorsal root ganglia (DRG) by quantitative reverse-transcriptase polymerase chain
      reaction (RT-PCR) analysis (QPCR) and specifically in retrogradely traced colonic
      neurons isolated via laser capture microdissection. Localization of ASIC
      expression in DRG was determined with fluorescence in situ hybridization (FISH)
      and retrograde tracing. QPCR of whole thoracolumbar DRG revealed and abundance of
      ASIC2 > ASIC1 > ASIC3. Similarly, FISH of all neurons in thoracolumbar DRG
      demonstrated that ASIC2 was expressed in the most (40 +/- 1%) neurons, followed
      by ASIC3 (24 +/- 1%), then ASIC1 (18 +/- 1%). Retrograde tracing from the distal
      colon labeled 4 +/- 1% of neurons in T10-L1 DRG. In contrast to whole DRG, FISH
      of colonic neurons showed ASIC3 expression in 73 +/- 2%, ASIC2 in 47 +/- 0.5%,
      and ASIC1 in 30 +/- 2%. QPCR of laser captured colonic neurons revealed that
      ASIC3 was the most abundant ASIC transcript, followed by ASIC1, then ASIC2. We
      conclude that ASIC1, 2, and 3 are expressed preferentially in colonic neurons
      within thoracolumbar DRG. In particular ASIC3, the least abundant in the general
      population, is the most abundant ASIC transcript in colonic neurons. The
      prevalence of ASIC3 in neurons innervating the colon supports
      electrophysiological data showing that it makes a major contribution to colonic
      mechanotransduction and therefore may be a target for the treatment of visceral
      pain.

PMID- 17177259
TI  - Species differences in the localization of soluble guanylyl cyclase subunits in
      monkey and rat brain.
AB  - Nitric oxide (NO) exerts most of its physiological effects through activation of
      a predominantly soluble guanylyl cyclase (sGC). In mammalian cells sGC exists as
      a heterodimer of alpha and beta subunits. Currently, four subunits (alpha1,
      alpha2, beta1, and beta2) have been characterized. We used in situ hybridization
      with subunit-specific 33P-labeled oligonucleotide probes to compare the
      anatomical distribution of sGC subunit mRNAs in rat and monkey brains. Message
      for all subunits except beta2 was detected in both species. The sGC subunit
      showing the highest expression and widest distribution was beta1. High expression
      for all subunits was found in basal ganglia, olfactory system, hippocampus,
      cortex, and cerebellum. Minor species differences in the relative distribution of
      alpha subunits were observed. In general, the alpha1 message was more prominent
      in monkey brain and the alpha2 message in rat brain. This was more evident in
      limbic areas and cerebellar cortex. Some differences were also observed in
      subunit laminar distribution in cerebral cortex. The limited species differences
      in sGC subunit distribution suggest that in primates, as occurs in rodents, the
      NO-cGMP signaling pathway will be involved in important brain functions such as
      memory formation, sensory processing, and behavior.

PMID- 17177260
TI  - Selective loss of dentate hilar interneurons contributes to reduced synaptic
      inhibition of granule cells in an electrical stimulation-based animal model of
      temporal lobe epilepsy.
AB  - Neuropeptide-containing hippocampal interneurons and dentate granule cell
      inhibition were investigated at different periods following electrical
      stimulation-induced, self-sustaining status epilepticus (SE) in rats.
      Immunohistochemistry for somatostatin (SOM), neuropeptide Y (NPY), parvalbumin
      (PV), cholecystokinin (CCK), and Fluoro-Jade B was performed on sections from
      hippocampus contralateral to the stimulated side and studied by confocal laser
      scanning microscopy. Compared to paired age-matched control animals, there were
      fewer SOM and NPY-immunoreactive (IR) interneurons in the hilus of the dentate
      gyrus in animals with epilepsy (40-60 days after SE), and 1, 3, and 7 days
      following SE. In the hilus of animals that had recently undergone SE, some SOM-IR
      and NPY-IR interneurons also stained for Fluoro-Jade B. Furthermore, there was
      electron microscopic evidence of the degeneration of SOM-IR interneurons
      following SE. In contrast, the number of CCK and PV-IR basket cells in epileptic
      animals was similar to that in controls, although it was transiently diminished
      following SE; there was no evidence of degeneration of CCK or PV-IR interneurons.
      Patch-clamp recordings revealed a diminished frequency of inhibitory postsynaptic
      currents in dentate granule cells (DGCs) recorded from epileptic animals and
      animals that had recently undergone SE compared with controls. These results
      confirm the selective vulnerability of a particular subset of dentate hilar
      interneurons after prolonged SE. This loss may contribute to the reduced
      GABAergic synaptic inhibition of granule cells in epileptic animals.

PMID- 17177261
TI  - Sex differences in projections from preoptic area aromatase cells to the
      periaqueductal gray in Japanese quail.
AB  - In many vertebrate species the medial preoptic area projects to a premotor
      nucleus, the periaqueductal central gray (PAG). This connection plays an
      important role in the control of reproductive behavior. In male Japanese quail
      (Coturnix japonica) specifically, the medial preoptic nucleus (POM), where
      various types of sensory inputs converge, is a critical site for the activational
      action of testosterone on male sexual behavior. To activate male copulatory
      behavior, testosterone must be aromatized to estradiol within the POM and
      aromatase-immunoreactive cells in the POM are the main source of projections to
      the PAG. The POM-PAG connection is thus an important functional circuit
      integrating the sensory with premotor components of sexual behavior. Contrary to
      what is observed in males, testosterone does not activate male-typical copulatory
      behavior in females and we investigated here via retrograde tracing methods
      whether this behavioral sexual difference is associated with a sex difference in
      connectivity between POM and PAG. Fluorescent microspheres were injected in the
      PAG of male and female quail and retrogradely labeled fluorescent cells counted
      in four fields of the POM in sections that had been immunolabeled for aromatase.
      Males had more aromatase-immunoreactive neurons projecting to the PAG than
      females and this difference was most prominent in the caudolateral part of the
      nucleus that has been specifically implicated in the control of male copulatory
      behavior. These data therefore support the hypothesis that sex differences in POM
      PAG connectivity are causally linked to the sex difference in the behavioral
      response to testosterone.

PMID- 17177262
TI  - Metabotropic glutamate receptor 4-immunopositive terminals of medium-sized spiny
      neurons selectively form synapses with cholinergic interneurons in the rat
      neostriatum.
AB  - Metabotropic glutamate receptor 4 (mGluR4) is localized mainly to presynaptic
      membranes in the brain. Rat neostriatum has been reported to contain two types of
      mGluR4-immunoreactive axon varicosities: small, weakly immunoreactive
      varicosities that were distributed randomly (type 1) and large, intensely
      immunoreactive ones that were often aligned linearly (type 2). In the present
      study, most type 1 terminals formed asymmetric synapses on dendritic spines,
      whereas type 2 terminals made symmetric synapses on dendritic shafts, showing
      immunoreactivity for GABAergic markers. After depletion of neostriatal neurons,
      type 2 but not type 1 varicosities were largely decreased in the damaged region.
      When medium-sized spiny neurons (MSNs) were labeled with Sindbis virus expressing
      membrane-targeted green fluorescent protein, mGluR4 immunoreactivity was observed
      on some varicosities of their axon collaterals in immunofluorescence and
      immunoelectron microscopies. Furthermore, type 2 varicosities were often positive
      for substance P but mostly negative for striatal interneuron markers and
      preproenkephalin. Thus, striatonigral/striato-entopeduncular MSNs are likely to
      be the largest source of type 2 mGluR4-immunopositive axon terminals in the
      neostriatum. Next, in the double-immunofluorescence study, almost all choline
      acetyltransferase (ChAT)-immunopositive and 41% of NK1 receptor-positive
      dendrites were heavily associated with type 2 mGluR4-immunoreactive varicosities.
      Neuronal nitric oxide synthase (nNOS)-positive dendrites, in contrast, seemed
      associated with only a few type 2 varicosities. Conversely, almost all type 2
      varicosities were closely apposed to NK1 receptor-positive dendrites that were
      known to be derived from cholinergic and nNOS-producing interneurons. These
      findings indicate that the mGluR4-positive terminals of MSN axon collaterals
      selectively form synapses with neostriatal cholinergic interneurons.

PMID- 17177263
TI  - Morphological and physiological properties of parvalbumin- and calretinin
      containing gamma-aminobutyric acidergic neurons in the substantia nigra.
AB  - Evidence for the existence of different populations of gamma-aminobutyric acid
      (GABA)-ergic neurons in the substantia nigra comes partially from anatomical
      studies, which have shown there to be little if any overlap between the calcium
      binding proteins parvalbumin and calretinin in individual neurons, suggesting
      that these may represent neuronal subtypes with distinct electrophysiological
      and/or anatomical properties. We obtained whole-cell recordings from neurons in
      the substantia nigra pars reticulata in rat brain slices and labeled them with
      biocytin, followed by immunocytochemical staining for parvalbumin and calretinin.
      In other cases, neurons were retrogradely labeled from the thalamus or tectum and
      immunocytochemically identified to determine their projection sites.
      Intracellularly stained neurons were found to have a variety of somatic sizes and
      shapes. Reconstructions revealed that all parvalbumin- and calretinin-positive
      neurons issued at least one axon collateral, which ramified within the substantia
      nigra pars reticulata and/or pars compacta. Local collaterals were of medium
      caliber and branched modestly, expressing many long, smooth segments that then
      issued numerous en passant or terminal boutons, consistent with previous in vivo
      studies. There were no clear differences in the electrophysiological or
      morphological properties of neurons expressing parvalbumin or calretinin.
      Retrograde tracing experiments revealed that both parvalbumin- and calretinin
      containing neurons project nonpreferentially to the thalamus or tectum. In sum,
      the parvalbumin- and calretinin-containing GABAergic neurons of the substantia
      nigra pars reticulata cannot be differentiated on the basis of their
      electrophysiological properties, morphological properties, or target nuclei, and
      both parvalbumin- and calretinin-containing projection neurons issue local axon
      collaterals that arborize within the substantia nigra.

PMID- 17177265
TI  - Prenatal detection and outcome of congenital diaphragmatic hernia: a French
      registry-based study.
AB  - OBJECTIVES: To describe the true incidence, prenatal detection rate and fetal
      outcome of congenital diaphragmatic hernia (CDH) in a systematically registered
      population over an 18-year period and to determine any change in trends over
      time. METHODS: This was a retrospective study of all cases of CDH registered in
      the Central-Eastern France Birth Defects Registry from 1986 to 2003. All fetuses
      and infants up to 1 year of age diagnosed with CDH were registered, including
      miscarriages later than 22 weeks of gestation, stillbirths and terminations of
      pregnancy (TOP). Routine prenatal screening consisted of three ultrasound
      examinations and there was no upper limit of gestational age for TOP. RESULTS:
      Five hundred and one cases of CDH were identified from a total of 1 835 022 live
      births (2.7 cases per 10 000 live births). The overall prenatal detection rate
      was 54%. There was a significant increase over time in the detection rate mainly
      for associated CDH and left-sided CDH (P < 0.0001), and in the proportion of
      neonates delivered in tertiary centers (P < 0.0001). The overall survival rate at
      discharge was 47% and this increased significantly over time for isolated CDH (P
      = 0.04), whereas it was lower and remained stable for associated CDH (P = 0.64).
      The TOP rate for isolated CDH did not vary significantly in contrast to that for
      associated CDH cases in which the TOP rate increased over time, progressively
      replacing the neonatal death rate (P = 0.01). CONCLUSIONS: Over an 18-year
      period, this large population-based study demonstrated increasing prenatal
      detection rates for associated CDH and left-sided CDH and confirmed an increasing
      survival rate mainly for isolated CDH.

PMID- 17177264
TI  - Online workbenches for neural network connections.
AB  - The nervous system is the most complex object we know of. It is a spatially
      distributed, functionally differentiated network formed by axonal connections
      between defined neuron populations and effector cells. Computer science provides
      exciting new tools for archiving, analyzing, synthesizing, and modeling on the
      Web vast amounts of frequently conflicting and incomplete qualitative and
      quantitative data about the organization and molecular mechanisms of neural
      networks. To optimize conceptual advances in systems neuroscience, it is
      important for the research and publishing communities to embrace three exercises:
      using defined nomenclatures; populating databases; and providing feedback to
      developers about improved design, performance, and functionality of knowledge
      management systems and associated visualization tools.

PMID- 17177266
TI  - Rhabdomyomatous hamartomata of the pharyngeal region with bilateral microtia and
      aural atresia: a new association?
AB  - BACKGROUND: Bilateral microtia with aural atresia is rare. Rhabdomyomatous
      hamartomata containing salivary tissue, situated bilaterally and symmetrically
      simulating the palatine (faucial) tonsils, has apparently not been reported. We
      present the combination of these findings in two unrelated patients. CASES: In
      the first case, the patient was exposed prenatally to 13-cis-retinoic acid
      (isotretinoin) and has typical features of this exposure, including bilateral
      microtia with aural atresia and bilateral 7th nerve palsies. Due to symptoms of
      obstructive sleep apnea, patient 1 had a "tonsillectomy" and adenoidectomy.
      Histopathologic studies demonstrated rhabdomyomatous hamartomata containing
      salivary and striated muscle tissue in place of the palatine tonsils. In the
      second case, the patient had been prenatally exposed to alcohol, cocaine, and
      marijuana. He has been noted to have developmental delay and behavioral issues in
      addition to bilateral microtia with aural atresia. "Tonsillectomy" and
      adenoidectomy were performed to alleviate chronic upper respiratory infections
      and snoring. Again, histopathologic studies of the tissue submitted as "tonsil"
      demonstrated rhabdomyomatous hamartomata containing salivary and muscle tissue.
      Although an extended banded karyotype and subtelomere panel were normal, a
      genetic etiology for the second patient's features cannot be excluded.
      CONCLUSIONS: We hypothesize that the findings of bilateral microtia with aural
      atresia and rhabdomyomatous hamartomata containing salivary and muscle tissue in
      the area of the palatine tonsils may represent a newly recognized association,
      which may have a teratogenic and/or genetic etiology.

PMID- 17177267
TI  - Genetic variations of the CDC2L2 gene are associated with type 2 diabetes in a
      Han Chinese cohort.
AB  - OBJECTIVE: The purpose of the present study was to study the potential
      association of CDC2L2 variations with type 2 diabetes (T2D). METHODS: SNPs
      (single nucleotide polymorphisms) were extensively screened across the CDC2L2
      gene by the site-specific PCR method ARMS (Amplification Refractory Mutation
      System). The identified novel polymorphisms were further evaluated in a Han
      Chinese cohort comprising of 467 patients with diabetes and 569 nondiabetic
      controls. In addition, 76 parent-offspring trios were also included in this
      association study. The case-control and TDT/sibTDT studies are applied for
      association analysis in this study. RESULTS: Seven loci (rs1059831, SNP33,
      rs7528782, SNP11, SNP36, rs11488590 and SNP30) were shown to be significantly
      associated with T2D in unrelated individuals (p < 0.05). When individuals were
      stratified by age, sex and body mass index (BMI), the SNP11 was shown to be
      strongly associated with female patients with T2D, patients whose age was over 45
      years and individuals whose BMI was less than 23 (p = 0.018, 0.011 and 0.0089,
      respectively). However, it was not replicated in the family-based TDT/sibTDT
      analysis (p = 0.085, OR = 0.63 (CI 95% 0.34-1.06)). CONCLUSION: Our data
      suggested that the CDC2L2 gene may contribute to the susceptibility of type 2
      diabetes in the northern Han Chinese population, but further studies are needed
      to replicate these findings.

PMID- 17177268
TI  - The development and evaluation of a measure to assess cancer survivors' unmet
      supportive care needs: the CaSUN (Cancer Survivors' Unmet Needs measure).
AB  - BACKGROUND: Many cancer survivors experience ongoing morbidity over the
      survivorship continuum and their supportive care needs have yet to be
      comprehensively assessed. METHODS: This study aimed to develop and empirically
      evaluate a self-report measure of cancer survivors' supportive care needs. In
      Phase I, questionnaire items were generated based upon previous qualitative
      research that identified both unique and shared needs in survivors and their
      partners; items were constructed into the Cancer Survivors' Unmet Needs measure
      (CaSUN). In Phase 2, the CaSUN was completed by 353 cancer survivors who had been
      diagnosed with cancer between 1 and 15 years earlier and were currently disease
      free. RESULTS: After modification, the CaSUN included 35 unmet need items, 6
      positive change items and an open-ended question. Good acceptability, internal
      consistency and validity were demonstrated, although test-retest reliability was
      low. Maximum likelihood factor analysis identified five discrete factors:
      Existential Survivorship, Comprehensive Care, Information, Quality of Life and
      Relationships. CONCLUSIONS: Preliminary data indicates that the CaSUN meets the
      majority of psychometric criteria for assessment measures, although its low test
      retest reliability awaits further investigation. The CaSUN will facilitate the
      evaluation of supportive care services and generation of service delivery
      recommendations for cancer survivors.

PMID- 17177269
TI  - Synthesis and properties of cyclic acetal biomaterials.
AB  - There is an increasing need to develop new biomaterials as tissue engineering
      scaffolds. Unfortunately, many of the materials that have been studied for these
      purposes are polyesters that hydrolytically degrade into acidic products, which
      may harm the surrounding tissue, and lead to accelerated degradation of the
      biomaterial. To overcome this disadvantage, a novel class of biomaterials based
      on a cyclic acetal unit has been created. Specifically, materials based upon the
      monomer 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol
      diacrylate (EHD) is examined. This study investigates the effects of fabrication
      parameters, including initiator content, volume of diluent, and volume of
      accelerant, on several properties of EHD networks. Twelve different formulations
      were fabricated by varying the three parameters in a factorial design. The
      effects of the fabrication parameters on properties of the EHD networks were
      examined. Results show that the volume of accelerant most affected the EHD
      network gelation time, while the volume of diluent most affected the maximum
      reaction temperature, sol fraction, and degree of swelling. Cell viability on the
      EHD networks varied between (18 +/- 6)% and (57 +/- 10)% of the control at 4 h,
      and between (36 +/- 14)% and (140 +/- 50)% of the control at 8 h. These results
      indicate that it is possible to control the properties of the EHD networks by
      varying the fabrication parameters, and that EHD networks support a viable cell
      population.

PMID- 17177272
TI  - Interval estimation of the risk difference in non-compliance randomized trials
      with repeated binary measurements.
AB  - In a randomized clinical trial (RCT), we often encounter non-compliance with the
      treatment protocol for a subset of patients. The intention-to-treat (ITT)
      analysis is probably the most commonly used method in a RCT with non-compliance.
      However, the ITT analysis estimates 'the programmatic effectiveness' rather than
      'the biological efficacy'. In this paper, we focus attention on the latter index
      and consider use of the risk difference (RD) to measure the effect of a
      treatment. Based on a simple additive risk model proposed elsewhere, we develop
      four asymptotic interval estimators of the RD for repeated binary measurements in
      a RCT with non-compliance. We apply Monte Carlo simulation to evaluate and
      compare the finite-sample performance of these interval estimators in a variety
      of situations. We find that all interval estimators considered here can perform
      well with respect to the coverage probability. We further find that the interval
      estimator using a tanh(-1)(x) transformation is probably more precise than the
      others, while the interval estimator derived from a randomization-based approach
      may cause a slight loss of precision. When the number of patients per treatment
      is large and the probability of compliance to an assigned treatment is high, we
      find that all interval estimators discussed here are essentially equivalent.
      Finally, we illustrate use of these interval estimators with data simulated from
      a trial of using macrophage colony-stimulating factor to reduce febrile
      neutropenia incidence in acute myeloid leukaemia patients.

PMID- 17177270
TI  - S. epidermidis biofilm formation: effects of biomaterial surface chemistry and
      serum proteins.
AB  - Most infections due to implanted cardiovascular biomaterials are initiated by
      bacterial adhesion of Staphylococcus epidermidis, followed by colonization and
      biofilm formation on the surface of the implant. This study examined the role of
      serum proteins and material surface chemistry in the formation of S. epidermidis
      biofilm on polyurethanes (Elasthane 80A, hydrophobic) modified with polyethylene
      oxide (Elasthane 80A-6PEO, hydrophilic) and fluorocarbon (Elasthane 80A-6F,
      hydrophobic). Initial adhesion, aggregation, biofilm thickness, viability, and
      slime formation of S. epidermidis strain, RP62A in phosphate buffered saline
      (PBS), tryptic soy broth (TBS), and 20% pooled human serum was quantified. In the
      presence of adsorbed serum proteins, initial bacterial adhesion was suppressed
      significantly to <2% relative to adhesion in TSB or PBS. However, adhesion,
      aggregation, and proliferation increased dramatically in the 12-24 h period on
      Elasthane 80A and Elasthane 80A-6F, which resulted in an extensive network of
      biofilm. A contrasting trend was observed on the hydrophilic Elasthane 80A-6PEO
      surface, with minimal bacterial adhesion, which decreased steadily over 24 h. In
      the presence of serum proteins, an increasingly thick ( approximately 20 mum)
      biofilm formed on the hydrophobic surfaces over 48 h whereas the formation of a
      mature biofilm on the hydrophilic surface was impeded with few viable bacteria
      present over 48 h. Furthermore, slime was detected during the initial phase of
      bacterial adhesion at 2 h and increased over time with the formation of biofilm.
      These results have shown that while initial S. epidermidis adhesion is suppressed
      in the presence of adsorbed proteins, inter-bacterial adhesion possibly aided by
      slime production leads to the formation of a robust mature biofilm. Also,
      biomaterial surface chemistry affected biofilm formation and, most notably,
      polyethylene oxide significantly inhibited S. epidermidis biofilm formation over
      48 h in vitro.

PMID- 17177273
TI  - Employment-contingent health insurance, illness, and labor supply of women:
      evidence from married women with breast cancer.
AB  - We examine the effects of employment-contingent health insurance (ECHI) on
      married women's labor supply following a health shock. First, we develop a
      theoretical framework that examines the effects of ECHI on the labor supply
      response to a health shock, which suggests that women with ECHI are less likely
      to reduce their labor supply in response to a health shock, relative to women
      with health insurance through their spouse's employer. Second, we empirically
      examine this relationship based on labor supply responses to breast cancer. We
      find that health shocks decrease labor supply to a greater extent among women
      insured by their spouse's policy than among women with health insurance through
      their own employer, suggesting that ECHI creates incentives to remain working
      when faced with a serious illness.

PMID- 17177274
TI  - Reduction in orofacial clefts following folic acid fortification of the U.S.
      grain supply.
AB  - BACKGROUND: Folic acid fortification in the United States became mandatory
      January 1, 1998, to reduce the occurrence of neural tube defects (NTDs). We
      evaluated the impact of folic acid fortification on orofacial clefts using United
      States birth certificate data for 45 states and the District of Columbia.
      METHODS: Prevalence ratios (PRs) were calculated comparing orofacial cleft
      prevalence among births prefortification (1/1990-12/1996) and postfortification
      (10/1998-12/2002), based on fortification status at conception. The JoinPoint
      Regression Program and exponentially weighted moving average charts (EWMA) were
      used to assess the timing of any statistically significant changes in prevalence.
      Data were stratified by maternal race/ethnicity, age, smoking, and timing of
      prenatal care. RESULTS: Orofacial clefts declined following folic acid
      fortification (PR=0.94; 95% CI: 0.92-0.96). The EWMA chart flagged a significant
      decrease in the fourth quarter of 1998. The JoinPoint graph had one change in
      slope, with a significant quarterly percent change (-0.34) between 1996 and 2002.
      The decline in orofacial clefts occurred in non-Hispanic Whites but not other
      racial/ethnic groups, nonsmokers but not women who reported smoking during
      pregnancy, and women who received prenatal care in the first trimester but not
      women who began receiving care later in pregnancy. CONCLUSION: Folic acid
      fortification in the United States was associated with a small decrease in
      orofacial cleft prevalence, with the timing of the decline consistent with the
      introduction of fortification. The decline is much smaller than that observed for
      NTDs, but nonetheless suggests an additional benefit of this public health
      intervention.

PMID- 17177275
TI  - Three-dimensional investigation and scoring of extracellular matrix remodeling
      during lung fibrosis using multiphoton microscopy.
AB  - The organization of collagen during fibrotic processes is poorly characterized
      because of the lack of appropriate methodologies. Here we show that multimodal
      multiphoton microscopy provides novel insights into lung fibrosis. We
      characterize normal and fibrotic pulmonary tissue in the bleomycin model, and
      show that second-harmonic generation by fibrillar collagen reveals the micrometer
      scale three-dimensional spatial distribution of the fibrosis. We find that
      combined two-photon excited fluorescence and second-harmonic imaging of unstained
      lung tissue allows separating the inflammatory and fibrotic steps in this
      pathology, underlining characteristic features of fibroblastic foci in human
      Idiopathic Pulmonary Fibrosis samples. Finally, we propose phenomenological
      scores of lung fibrosis and we show that they unambiguously sort out control and
      treated mice, with a better sensitivity and reproducibility in the subpleural
      region. These results should be readily generalized to other organs, as an
      accurate method to assess extracellular matrix remodeling during fibrosis.

PMID- 17177276
TI  - Six-color segmentation of multicolor images in the infection studies of Listeria
      monocytogenes.
AB  - Multiple immunofluorescent staining is a powerful strategy for visualizing the
      spatial and temporal relationship between antigens, cell populations, and tissue
      components in histological sections. To segment different cell populations from
      the multicolor image generated by immunostaining based on color addition theory,
      a systems approach is proposed for automatic segmentation of six colors. After
      image acquisition and processing, images are automatically segmented with the
      proposed approach and six-pseudo channels for individual or colocalized
      fluorescent dye are generated to distinguish different cell types. The principle
      of this approach is the classification of each pixel into one of six colors (red,
      green, blue, yellow, magenta, and cyan) by choosing the minimal angular deviation
      between the RGB vector of the given pixel and six classically defined edge
      vectors. In the present infection studies of Listeria monocytogenes, the new
      multicolor staining methods based on the color addition were applied and the
      proposed color segmentation was performed for multicolor analysis. Multicolor
      analysis was accomplished to study the migration and interaction of Listeria and
      different cell subpopulations such as CD4CD25 double positive T regulatory cells;
      we also visualized simultaneously the B cells, T cells, dendritic cells,
      macrophages, and Listeria in another experiment. After Listeria infection, ERTR9
      macrophages and dendritic cells formed cluster with Listeria in the infection
      loci. The principle of color addition and the systems approach for segmentation
      may be widely applicable in infection and immunity studies requiring multicolor
      imaging and analysis. This approach can also be applied for image analysis in the
      multicolor in vivo imaging, multicolor FISH or karyotyping or other studies
      requiring multicolor analysis.

PMID- 17177277
TI  - Morphological changes in mouse embryos cryopreserved by different techniques.
AB  - Cryopreservation of mammalian embryos is an important tool for the application of
      reproductive biotechnologies. Subjective evaluation to determine embryo viability
      is often used. The determination of the best cryopreservation protocol depends on
      morphological and molecular analysis of cellular injuries. The main objective of
      this study was to compare two methods of cryopreservation by assessing
      morphological alterations of frozen embryos using light, fluorescence, and
      transmission electron microscope. Fresh (control), slow frozen, and vitrified
      mouse embryos were composed. To evaluate the viability of the embryos, the cell
      membrane integrity was assessed using Hoechst33342 and propidium iodide (H/PI)
      staining. Morphological analyses using hematoxylin and eosin (HE) staining were
      performed to test different techniques (in situ, paraffin, and historesin) by
      both light and fluorescence microscopy. Transmission electron microscope was used
      to detect ultrastructural alterations in Spurr- and Araldite-embedded samples.
      H/PI staining detected more membrane permeability in the vitrification (69.8%)
      than in the slow freezing (48.4%) or control (13.8%) groups (P < 0.001).
      Historesin-embedded samples showed to be more suitable for morphological analyses
      because cellular structures were better identified. Nuclear evaluation in
      historesin sections showed the induction of pycnosis in slow freezing and
      vitrification groups. Cytoplasm evaluation revealed a condensation and an
      increase in eosinophilic intensity (indicating apoptosis) in the slow freezing
      group, and weakly eosinophilic structures and degenerated cells (indicating
      oncosis) in the vitrification group (P < 0.05). Ultrastructural analyses
      confirmed HE morphological findings. It was concluded that both cryopreservation
      techniques resulted in oncosis and apoptosis injuries. However, vitrification
      caused more severe cellular alterations and reduced embryonic viability compared
      to slow freezing.

PMID- 17177278
TI  - Quality improvement and its impact on the use and equality of outpatient health
      services in India.
AB  - This paper examines the impact of quality improvements in conjunction with user
      fees on the utilization and equality of outpatient services at a range of public
      sector health facilities in India. Project impact on outpatient visits was
      estimated via the difference-in-difference method using pooled time series visit
      data from project and control facilities. The results indicate that the quality
      improvements significantly increased visits at all facility types. The project
      effect was largest at primary health center (PHC) and community health center
      (CHC), followed by district hospital (DH) and female district hospital (FDH). Pro
      rich inequalities in outpatient visits increased at DHs and FDHs while at CHCs
      and PHCs the distribution remained equitable. This suggests that quality
      improvements at public sector health facilities can increase utilization of
      outpatient services in the presence of nominal user fees, but can also promote
      greater inequality favoring the better-off. At the referral hospital level,
      quality improvements should be made in conjuction with programs which encourage
      utilization by the poor. In contrast, the benefit of quality improvements at PHCs
      and CHCs is equitably distributed.

PMID- 17177279
TI  - Genomics and developmental risk assessment.

PMID- 17177280
TI  - Blood bank issues associated with red cell exchanges in sickle cell disease.
AB  - Sickle cell disease (SCD) patients are prone to develop complications that
      include stroke, acute chest syndrome, and other crises. Some of these
      complications require chronic transfusion therapy or red cell exchange (RCE),
      either for therapeutic or prophylactic reasons. Due to a discrepancy of red cell
      antigens between African Americans and Caucasians (majority blood donors), the
      incidence of alloantibody formation is very high, which makes it difficult to
      find compatible red cell units, especially for urgent RCE. Some of the above
      conditions require immediate oxygen delivery to the tissues. Thus, SCD patients
      undergoing RCE should receive red blood cells with special attributes that
      include matching for Rh and Kell blood group antigens; RBCs should be fresh in
      order to provide (1) immediate oxygen delivery and (2) longer surviving cells to
      reduce the interval between RCE. Also, these units should be pre-storage
      leukoreduced to prevent febrile non-hemolytic reactions and screened for sickle
      cell traits to avoid transfusing red cells containing HbS. This requires a
      concerted effort between the apheresis unit, the local blood bank, and the
      central blood supplier.

PMID- 17177281
TI  - Diploid sperm produced by artificially sex-reversed clone loaches.
AB  - Clone loaches reproduce unisexually in a wild population of Hokkaido Island,
      Japan. These clone loaches produce genetically identical unreduced eggs which
      develop to diploid individuals without any genetic contribution of sperm donors.
      In the present study, sex reversal of clone loaches was attempted and the
      reproductive potential of resultant clone males was examined. Clone loaches
      administered 0.5 ppm of 17-alpha methyltestosterone (MT) for 30 days from 1 month
      after hatching differentiated into physiological males. These sex-reversed clone
      males produced fertile spermatozoa with a diploid DNA content. Diploid
      spermatozoa had significantly larger heads than normal haploid sperm, but had a
      normal shape showing a head, mid-piece, and tail. The motility of diploid
      spermatozoa was low after ambient water was added. Concentration of diploid
      spermatozoa per unit of sperm was lower than that of control haploid spermatozoa.
      Microsatellite genotyping revealed that triploid progeny from the cross between a
      normal diploid female and a sex-reversed clone male had two alleles specific to
      the diploid clone male and one allele of the mother loach. These results
      indicated that the sex-reversed clone males produced fertile diploid spermatozoa
      genetically identical to the clone lineage.

PMID- 17177282
TI  - Antler regeneration: a dependent process of stem tissue primed via interaction
      with its enveloping skin.
AB  - Deer antlers are unique mammalian appendages in that each year they are cast and
      fully regenerate from permanent bony protuberances, called pedicles. In a
      previous study, we found that there is a difference in the degree of association
      between pedicle bone and its enveloping skin: tight at the distal third and loose
      at the proximal two thirds of a pedicle stump. The distal part has been termed
      the "potentiated" region, and the proximal part the "dormant" region. In the
      present study, pedicle stumps were artificially created in yearling sika deer by
      cutting off the tissue distal to either the potentiated or the dormant region. A
      piece of impermeable membrane was then inserted into the space between the bone
      and the skin of each treated pedicle stump, while the control pedicles had the
      same surgery without membrane insertion. The results showed that the inserted
      membrane blocked pedicle skin participation in the process of antler
      regeneration. All three potentiated bony pedicle stumps regenerated skin-less
      antlers; whereas, one of the three dormant bony pedicle stumps failed to
      regenerate any antler tissue. The other two dormant stumps eventually regenerated
      normal antlers; however, this only occurred after loss of the inserted membrane.
      No antler tissue regenerated from the dormant stumps while the inserted membrane
      remained in place (up to 55 days). All control pedicle stumps regenerated normal
      antlers. Therefore, we conclude that it is the pedicle bone, but not pedicle
      skin, that gives rise to regenerating antlers, and that pedicle bone can acquire
      the potential to regenerate an antler only when it is primed via interaction with
      its enveloping skin.

PMID- 17177283
TI  - Molecular analyses of the intestinal microbiota of chimpanzees in the wild and in
      captivity.
AB  - Little information is available regarding the intestinal bacteria of chimpanzees
      in the wild, due to the technical difficulties of studying intestinal bacteria in
      the field. In this study, molecular-based bacterial analyses were performed to
      overcome this difficulty because polymerase chain reaction (PCR)-based methods,
      such as temperature gradient gel electrophoresis (TGGE) and amplified ribosomal
      DNA restriction analysis (ARDRA), of the bacterial 16S rRNA gene can be applied
      to ethanol-fixed fecal samples. The common presence of bacteria belonging to the
      Clostridium rRNA sub-group XIVa, such as Ruminococcus obeum and Eubacterium sp.,
      was indicated for Bossou wild chimpanzees by ARDRA. TGGE on partial 16S rDNA
      followed by hierarchical clustering analysis showed a systematic difference in
      the composition of intestinal microbiota between wild and captive chimpanzees.
      However, several TGGE bands commonly shared by wild and captured chimpanzees were
      excised, and their sequences were obtained. They were suggested to be the
      Clostridium leptum subgroup bacteria, Lactobacillus gasseri-like bacterium, and
      Bifidobacterium pseudocatenulatum- or B. catenulatum-like bacterium. These may be
      considered as common intestinal bacteria for chimpanzees, and may be transmitted
      vertically over generations.

PMID- 17177284
TI  - Accounting for quality in the measurement of hospital performance: evidence from
      Costa Rica.
AB  - This paper provides insights into how Costa Rican public hospitals responded to
      the pressure for increased efficiency and quality introduced by the reforms
      carried out over the period 1997-2001. To that purpose we compute a generalized
      output distance function by means of non-parametric mathematical programming to
      construct a productivity index, which accounts for productivity changes while
      controlling for quality of care. Our results show an improvement in hospital
      performance mainly driven by quality increases. The adoption of management
      contracts seems to have contributed to such enhancement, more notably for small
      hospitals. Further, productivity growth is primarily due to technical and scale
      efficiency change rather than technological change. A number of policy
      implications are drawn from these results.

PMID- 17177286
TI  - Optimization of the methods for introduction of amine groups onto the silica
      nanoparticle surface.
AB  - The luminescent silica nanoparticle has attracted the researchers' concentration
      in bioanalysis recently. Its extensive application is based on the immobilization
      of various biomolecules such as deoxyribonucleic acid, antibody, and so forth
      onto the surface. By comparing different introduction methods of amine groups, it
      was confirmed that the "two-step" route is more preferable by adding tetraethyl
      orthosilicate and 3-aminopropyl-(triethoxyl)silane in sequence, to attain ideal
      amine-modified silica nanoparticles. On this basis, carboxyl groups were derived
      from amine groups on the nanoparticle surface and then were activated by 1-ethyl
      3-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxy-succinimide.
      Finally, mouse monoclonal antihuman CD71 antibody (McAb CD71) and transferrin
      were effectively linked with the carboxyl groups and successfully labeled the
      receptors in the membrane of fibroblast cells, respectively.

PMID- 17177287
TI  - Injecting partially digested cartilage fragments into a biphasic scaffold to
      generate osteochondral composites in a nude mice model.
AB  - This study proposed a novel scaffold with heterogeneous morphology that mimics
      the natural tissue. Its upper part contains a hollow cavity surrounded by a wall
      of poly(L-lactic-co-glycolic acid) (PLGA) porous membrane for injecting cartilage
      tissue and cells. An interconnecting porous structure located under the hollow
      cavity was made of composite materials that combined PLGA and beta-tricalcium
      phosphate (beta-TCP) to simulate the subchondral bone. Adult pig articular
      cartilage was cut and sieved into small fragments. The tissue fragments was
      partially digested by 0.1% collagenase for 0, 2, 4, and 6 h and injected into the
      hollow cavity of the biphasic scaffold. The biphasic scaffolds were then
      implanted into the subcutaneous pocket of nude mice for 4 weeks. No tissue
      bonding or new cartilaginous tissue formation was identified in the cartilage
      fragment without enzymatic treatment. The cartilage fragments digested with 2 h
      of collagenase digestion were partially integrated after implantation. The
      integrative properties of the cartilage fragment depended on the extent of
      enzymatic digestion. Releasing cells at the tissue surface enhanced confluence
      and bonding of the cartilage fragment matrix. Complete integration of the
      cartilage fragments and cartilage remodeling were achieved by digestion of the
      tissue fragments with 4 h of enzymatic treatment. The neocartilage grew from the
      upper hollow cavity into the lower PLGA/beta-TCP porous structure, forming an
      interface similar to that formed between cartilage and subchondral bone. This
      study combined the osteochondral scaffold and limited cartilage tissues to
      generate cartilage tissue in vivo intending for repairing full-thickness
      articular cartilage defects.

PMID- 17177285
TI  - Molecular profiles of mitogen activated protein kinase signaling pathways in
      orofacial development.
AB  - BACKGROUND: Formation of the mammalian orofacial region involves multiple
      signaling pathways regulating sequential expression of and interaction between
      molecular signals during embryogenesis. The present study examined the expression
      patterns of members of the MAPK family in developing murine orofacial tissue.
      METHODS: Total RNA was extracted from developing embryonic orofacial tissue
      during gestational days (GDs) 12-14 and used to prepare biotinylated cDNA probes,
      which were then denatured and hybridized to murine MAPK signaling pathways gene
      arrays. RESULTS: Expression of a number of genes involved in the (ERK1/2) cascade
      transiently increased in the embryonic orofacial tissue over the developmental
      period examined. Numerous members of the SAPK/JNK cascade were constitutively
      expressed in the tissue. Genes known to play a role in p38 MAPK signaling
      exhibited constitutive expression during orofacial development. Western blot
      analysis demonstrated that ERK2/1, p38, and SAPK/JNK kinases are present in
      embryonic orofacial tissue on each of GD 12, 13, and 14. By using phospho
      specific antibodies, active ERK was shown to be temporally regulated during
      orofacial development. Minimal amounts of active p38 and active SAPK/JNK were
      detected in orofacial tissue during GDs 12-14. CONCLUSIONS: Our study documents
      specific expression patterns of genes coding for proteins belonging to the
      ERK1/2, p38, and SAPK/JNK MAPK families in embryonic orofacial tissue. We also
      demonstrate that active, phosphorylated forms of ERK1/2 only were detected in the
      embryonic tissue investigated, suggesting a more central role for members of this
      family in embryonic orofacial development.

PMID- 17177288
TI  - Effect of pore size on in vitro cartilage formation using chitosan-based
      hyaluronic acid hybrid polymer fibers.
AB  - In this study, we successfully developed three-dimensional scaffolds fabricated
      from the chitosan-based hyaluronic acid hybrid polymer fibers, which can control
      the porous structure. To determine the adequate pore size for enhancing the
      chondrogenesis of cultured cells, we compared the behaviors of rabbit
      chondrocytes in scaffolds comprising different pore sizes (100, 200, and 400
      microm pore size). Regarding the cell proliferation, there was no significant
      difference among the three groups. On the other hand, glycosaminoglycan contents
      in the 400 microm group significantly increased during the culture period,
      compared with those in the other groups. The ratio of type II to type I collagen
      mRNA level was also significantly higher in the 400 microm group than in the
      other groups. These results indicate that our scaffold with 400 microm pore size
      significantly enhances the extracellular matrix synthesis by chondrocytes.
      Additionally, the current scaffolds showed high mechanical properties, compared
      with liquid and gel materials. The data derived from this study suggest great
      promise for the future of a novel fabricated material with relatively large pore
      size as a scaffold for cartilage regeneration. The biological and mechanical
      advantages presented here will make it possible to apply our scaffold to
      relatively wide cartilaginous lesions.

PMID- 17177289
TI  - Targeting microspheres and cells to polyethylene glycol-modified biological
      surfaces.
AB  - It has previously been demonstrated that damaged arterial tissue can be acutely
      modified with protein-reactive polyethylene glycol (PEG) to block undesirable
      platelet deposition. This concept might be expanded by employing PEG-biotin and
      its strong interaction with avidin for site-specific targeted delivery. Toward
      this end, cultured endothelial cells (ECs) were surface modified with PEG-biotin
      and the available biotin was quantified with flow cytometry. NeutrAvidin-coated
      microspheres and PEG-biotin modified ECs with NeutrAvidin as a bridging molecule
      were delivered under arterial shear stress to PEG-biotin modified ECs on a
      coverslip as well as scrape-damaged bovine carotid arteries. After incubation
      with a 10 mM solution for 1 min, 8 x 10(7) PEG-biotin molecules/EC were found and
      persisted for up to 120 h. Perfused microspheres adhered to NHS-PEG-biotin
      treated bovine carotid arteries with 60 +/- 16 microspheres/mm(2) versus 11 +/- 4
      microspheres/mm(2) for control arteries (p < 0.015). Similarly, 22 +/- 5 targeted
      ECs/mm(2) adhered to NHS-PEG-biotin treated bovine carotid arteries versus 6 +/-
      2 ECs/mm(2) for control arteries (p < 0.01). The targeting strategy demonstrated
      here might ultimately find application for drug delivery, gene therapy, or cell
      therapy where localization to specific labeled vascular regions is desired
      following catheter-based or surgical procedures.

PMID- 17177290
TI  - The role of the organ microenvironment in the biology and therapy of cancer
      metastasis.
AB  - By the time of diagnosis, primary neoplasms are biologically heterogeneous and
      contain subpopulations of cells with different metastatic potentials. The
      pathogenesis of a metastasis consists of many sequential steps that must be
      completed to produce clinically relevant lesions. During any of these steps,
      tumor cells interact with host factors in the microenvironment that the tumor
      cells can usurp. Treatment of metastasis can be directed against tumor cells
      and/or microenvironmental factors that support tumor growth, such as tumor
      associated blood vessels.

PMID- 17177291
TI  - Site-specific proteolysis of cyclooxygenase-2: a putative step in inflammatory
      prostaglandin E(2) biosynthesis.
AB  - Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in inflammatory
      prostanoid biosynthesis. Transcriptional, post-transcriptional, and post
      translational covalent modifications have been defined as important levels of
      regulation for COX-2 gene expression. Here, we describe a novel regulatory
      mechanism in primary human cells involving regulated, sequence-specific
      proteolysis of COX-2 that correlates with its catalytic activity and ultimately,
      the biosynthesis of prostaglandin E(2) (PGE(2)). Proinflammatory cytokines
      induced COX-2 expression and its proteolysis into stable immunoreactive fragments
      of 66, 42-44, 34-36, and 28 kDa. Increased COX-2 activity (PGE(2) release) was
      observed coincident with the timing and degree of COX-2 proteolysis with
      correlation analysis confirming a linear relationship (R(2) = 0.941). Inhibition
      of induced COX-2 activity with non-steroidal anti-inflammatory drugs (NSAIDs) and
      COX-2 selective inhibitors also abrogated cleavage. To determine if NSAID
      inhibition of proteolysis was related to drug-binding-induced conformational
      changes in COX-2, we assayed COX-inactive NSAID derivatives that fail to bind COX
      2. Interestingly, these compounds suppressed COX-2 activity and cleavage in a
      correlated manner, thus suggesting that the observed NSAID-induced inhibition of
      COX-2 cleavage occurred through COX-independent mechanisms, presumably through
      the inhibition of proteases involved in COX-2 processing. Corroborating this
      observation, COX-2 cleavage and activity were mutually suppressed by
      calpain/cathepsin protease inhibitors. Our data suggest that the nascent
      intracellular form of COX-2 may undergo limited proteolysis to attain full
      catalytic capacity.

PMID- 17177292
TI  - The commonality of plasticity underlying multipotent tumor cells and embryonic
      stem cells.
AB  - Aggressive cancer cells and pluripotent stem cells converge in their capacity for
      self-renewal, proliferation and plasticity. Recent studies have capitalized on
      these similarities by demonstrating that tumors arise from specific cancer stem
      cell populations that, in a manner reminiscent of normal stem cells, are able to
      both self-renew and give rise to a heterogeneous tumor population. This stem cell
      like function of aggressive cancer cells is likely attributable to the ectopic
      expression of embryonic factors such as Nodal and Cancer Testis Specific Antigens
      (CTAs), which maintain a functional plasticity by promoting pluripotency and
      immortality. During development, the expression of these embryonic factors is
      tightly regulated by a dynamic array of mediators, including the spatial and
      temporal expression of inhibitors such as Lefty, and the epigenetic modulation of
      the genome. In aggressive cancer cells, particularly melanoma, this balance of
      regulatory mediators is disrupted, leading to the aberrant expression of
      pluripotency-associated genes. By exposing aggressive cancer cells to embryonic
      microenvironments, this balance of regulatory mediators is restored, thereby
      reprogramming tumor cells to a more benign phenotype. These stem cell-derived
      mediators, as well as the genes they regulate, provide therapeutic targets
      designed to specifically differentiate and eradicate aggressive cancers.

PMID- 17177293
TI  - Role of PKA in the anti-Thy-1 antibody-induced neurite outgrowth of dorsal root
      ganglionic neurons.
AB  - Thy-1 is highly expressed in the mammalian nervous system. Our previous study
      showed that addition of anti-Thy-1 antibody to cultured dorsal root ganglionic
      (DRG) neurons promotes neurite outgrowth. In this study, we identified a novel
      signaling pathway mediating this event. Treatment with function-blocking anti-Thy
      1 antibodies enhanced neurite outgrowth of DRG neurons in terms of total neurite
      length, longest neurite length, and total neurite branching points. To elucidate
      the possible signal transduction pathway involved, activation of kinases was
      evaluated by Western blotting. Transient phosphorylation of protein kinase A
      (PKA) and mitogen-activated kinase kinase (MEK) was induced after 15 min of anti
      Thy-1 antibody treatment. Pretreatment with a PKA inhibitor (PKI) or an MEK
      inhibitor, PD98059, significantly decreased the neurite outgrowth response
      triggered by anti-Thy-1 antibody, indicating the involvement of both kinases. In
      addition, anti-Thy-1 antibody treatment also induced transient phosphorylation of
      cyclic AMP-response element-binding protein (CREB) and this effect was also
      blocked by a PKI or PD98059. Furthermore, the fact that PKI abolished anti-Thy-1
      antibody-induced MEK phosphorylation showed that PKA acts upstream of the MEK
      CREB cascade. In summary, the PKA-MEK-CREB pathway is a new pathway involved in
      the neurite outgrowth-promoting effect of anti-Thy-1 antibody.

PMID- 17177294
TI  - Apoptosis in medfly hemocytes is regulated during pupariation through FAK, Src,
      ERK, PI-3K p85a, and Akt survival signaling.
AB  - Focal adhesion kinase (FAK) and its downstream signaling targets are implicated
      in the process of apoptosis induced by external stimuli, in several mammalian
      systems. In this report, we demonstrate, that medfly (Ceratitis capitata)
      hemocytes do undergo apoptosis during larval development. In particular, we show
      using Western blot, ELISA and flow cytometry analysis, that FAK expression
      silencing in transfected by FAK double-stranded RNA (dsRNA) hemocytes, enhances
      twofold hemocyte apoptosis, by signaling through Src, MEK/ERK, and PI-3K/Akt
      signaling pathways. FAK expression silencing, in response to FAK dsRNA treatment,
      blocks partially the phosphorylation of its downstream targets. Pre-incubation of
      hemocytes, with specific inhibitors of FAK downstream signaling molecules,
      demonstrated that all these inhibitors reduced hemocyte viability and enhanced
      the magnitude of apoptosis about threefold. This data suggest that these pathways
      contribute to hemocyte survival and/or death during development. The expression
      and phosphorylation of FAK, Src, PI-3K p85a, Akt, and ERK signaling molecules
      appear to be dependent upon developmental stages. The expression and
      phosphorylation of the above signaling molecules, in annexin-positive and annexin
      negative hemocytes is also distinct. The maximum expression and phosphorylation
      of FAK, Src, PI-3K p85a, Akt, and ERK appeared in annexin-positive hemocytes, in
      both early and late apoptotic hemocytes. The novel aspect of this report is based
      on the fact that hemocytes attempt to suppress apoptosis, by increasing the
      expression/phosphorylation of FAK and, hence its downstream targets signaling
      molecules Src, ERK, PI-3K p85a, and Akt. Evidently, the basic survival pathways
      among insects and mammals appear to remain unchanged, during evolution.

PMID- 17177295
TI  - Inhibitory effect of TNF-alpha on the intestinal absorption of galactose.
AB  - Sepsis is a systemic response to infection in which toxins, such as bacterial
      lipopolysaccharide (LPS), stimulate the production of inflammatory mediators like
      the cytokine tumor necrosis factor alpha (TNF-alpha). Previous studies from our
      laboratory have revealed that LPS inhibits the intestinal absorption of L-leucine
      and D-fructose in rabbit when it was intravenously administered, and that TNF
      alpha seems to mediate this effect on amino acid absorption. To extend this work,
      the present study was designed to evaluate the possible effect of TNF-alpha on D
      galactose intestinal absorption, identify the intracellular mechanisms involved
      and establish whether this cytokine mediates possible LPS effects. Our findings
      indicate that TNF-alpha decreases D-galactose absorption both in rabbit
      intestinal tissue preparations and brush-border membrane vesicles. Western blot
      analysis revealed reduced amounts of the Na+/glucose cotransporter (SGLT1)
      protein in the plasma membrane attributable to the cytokine. On the contrary, TNF
      alpha increased SGLT1 mRNA levels. Specific inhibitors of the secondary
      messengers PKC, PKA, the MAP kinases p38 MAP, JNK, MEK1/2 as well as the
      proteasome, diminished the TNF-alpha-evoked inhibitory effect. LPS inhibition of
      the uptake of the sugar was blocked by a TNF-alpha antagonist. In conclusion, TNF
      alpha inhibits D-galactose intestinal absorption by decreasing the number of
      SGLT1 molecules at the enterocyte plasma membrane through a mechanism in which
      several protein-like kinases are involved.

PMID- 17177296
TI  - Genetic relationship of Torque Teno virus (TTV) between humans and camels in
      United Arab Emirates (UAE).
AB  - Torque Teno Virus (TTV) species-cross infection has been documented. However, the
      genetic relationship between human and animal TTV remains uncertain. In this
      study, genotypic characterization of TTV in different Camel specimens from the
      United Arab Emirates (UAE) was undertaken for comparison with human UAE TTV. A
      total of 56 specimens: 34 sera, 14 raw, and 8 pasteurized milk samples were
      tested for TTV. The results showed that the rate of infection was, 38.2% (13/34),
      35.7% (5/14), and 100% (8/8), for the samples of sera, raw, and pasteurized milk
      respectively. The 5'untranslated region (5'UTR) of 23 clones that were generated
      from PCR products amplified from Camel samples (three sera, three raw, and two
      pasteurized milk samples) were subjected to sequence analysis. The camel TTV
      clones were classified as genotype 11 (47.8%), group 5 (43.5%), and SENV-H or
      genotype 16 (8.7%) which are among the predominant genotypes found in humans in
      the UAE. Phylogenetic analysis of representative sequences revealed that the
      similarity between isolates from camels and humans is 92%-97% for the same
      genotypes. The data lead to the conclusion that camels and humans share a common
      source of TTV infection in the UAE.

PMID- 17177297
TI  - Local alendronate increases fixation of implants inserted with bone compaction:
      12-week canine study.
AB  - Bone compaction has been shown to increase initial implant fixation. Furthermore,
      bone compaction creates a peri-implant zone of autograft that exerts
      osteoconductive properties. We have previously shown that locally applied
      bisphosphonate (alendronate) at 4-week observation can preserve the autograft
      generated by bone compaction. We now investigate whether the increased amount of
      autograft, seen at 4 weeks, can increase implant osseointegration and
      biomechanical fixation. Porous-coated titanium implants were bilaterally inserted
      with bone compaction into the proximal part of tibia of 10 dogs. On the right
      side, local bisphosphonate was injected into the bone cavity prior to bone
      compaction immediately prior to implant insertion. On the left side, saline was
      used as control. Observation period was 12 weeks. Locally applied bisphosphonate
      significantly increased biomechanical implant fixation (approximately twofold),
      bone-to-implant contact (1.2-fold), and peri-implant bone volume fraction (2.3
      fold). This study indicates that local alendronate treatment can increase early
      implant osseointegration and biomechanical fixation of implants inserted by use
      of bone compaction. Long term effects remain unknown.

PMID- 17177299
TI  - Human herpesvirus 8: serovprevalence and correlates in tumor patients from
      Xinjiang, China.
AB  - Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated
      herpesvirus, is etiologically associated with Kaposi's sarcoma and other
      lymphoproliferative diseases. Although HHV-8 prevalence exhibits considerable
      variation in different geographic regions and populations, the incidence of
      Kaposi's sarcoma appear to increase in areas with a high prevalence rate. In this
      study, an enzyme-linked immunosorbent assay based on mixed antigens of HHV-8
      ORF(73), ORF(65), and K8.1 in the antigenic region was established and used to
      determine viral prevalence estimates and risk factors associated with HHV-8
      infection. Of 482 tumor patients studied, the overall seropositivity of HHV-8 was
      25.5%. Notably, Han people, who were immigrants or descendents of immigrants from
      inland of China, exhibited 26.4% seropositivity. This is similar to that observed
      in Uygur people, a local ethnic group with a high prevalence of HHV-8 infection
      and incidence of Kaposi's sarcoma. While there was no significant difference in
      patients with different tumors, HHV-8 seroprevalence was higher in individuals
      with malignant diseases. Logistic regression analysis suggests that the age is a
      risk factor associated with HHV-8 infection, with prevalence increasing from
      12.5% under 20-27.5% above 50. These results suggest that unlike other parts of
      mainland of China, Xinjiang is an area with a high prevalence of HHV-8 infection.

PMID- 17177298
TI  - Hepatitis C Virus p7 membrane protein quasispecies variability in chronically
      infected patients treated with interferon and ribavirin, with or without
      amantadine.
AB  - A clinical study was carried out to compare the response rate of two groups of
      non-responder (NR) hepatitis C virus (HCV) genotype 1 chronically infected
      patients treated with interferon and ribavirin, with or without amantadine. The
      viral load decreased more markedly in the group treated by tritherapy including
      amantadine, but the response rate at the end of treatment was not significantly
      different between bitherapy and tritherapy. As amantadine could have an antiviral
      effect on the ion channel activity of the p7 HCV protein, the p7 quasispecies was
      characterized by cloning and sequencing. Sequence data were analyzed to determine
      the pattern and significance of p7 genetic heterogeneity and a possible
      relationship with therapy. Subtype differences were confirmed between p7 HCV
      genotypes 1a and 1b, and quasispecies analysis showed a reduction of genetic
      diversity in subtype 1a, but not 1b, during tritherapy. However, the absence of
      changes at numerous positions, as well as the conservative changes at other
      positions, indicated the high conservation of the p7 structure. Residue His-17,
      proposed to interact with amantadine, was fully conserved in both subtypes 1a and
      1b, independently of amantadine administration. In conclusion, although the
      analysis of the p7 sequences revealed a selective pressure during therapy, no
      specific residues appeared to be linked to the effect of amantadine on viral
      decline. These results suggest that the potential antiviral effect of amantadine
      might be non-specific and related to a reduction in endosomal acidification and
      therefore reduced viral entry of HCV via its pH-dependent pathway.

PMID- 17177300
TI  - Human herpesvirus 8 and human herpesvirus 2 infections in prison population.
AB  - Incarcerated persons have high rates of infectious diseases. Few data on the
      prevalence of sexually transmitted diseases in prisoners are available. This
      multi-center cross-sectional study enrolled 973 inmates from eight Italian
      prisons. Demographic and behavioral data were collected using an anonymous
      standardized questionnaire and antibodies to HIV, HCV, HBV, HSV-2, and HHV-8 were
      detected in a blood sample obtained from each person at the time of the
      enrollment in the study. Two hundred and two out of the 973 subjects (20.7%) had
      antibodies against HHV-8. HHV-8-seropositive subjects were more likely to be
      older than 30 years with a higher educational level. HHV-8 infection was
      associated significantly with HBV (P < 0.001) and HSV-2 (P = 0.004)
      seropositivity and with previous imprisonments. Multivariate analysis showed that
      HHV-8 infection in Italian inmates was associated with HBV (P < 0.001) and HSV-2
      (P = 0.002) seropositivity otherwise among foreigners inmates HHV-8 was
      significantly associated with HBV infection (P = 0.05). One hundred and eighty
      six (21.2%) prisoners had anti-HSV-2 antibodies. At multivariate analysis HSV-2
      positivity was significantly associated with HIV (P < 0.001) and HHV-8 infections
      (P = 0.003), whereas it was inversely associated with HCV infection (0.004). A
      relatively high seroprevalence of HHV-8 and HSV-2 among Italian prison inmates
      was found. The association of HHV-8 and HSV-2 infections suggest sexual
      transmission of these viruses among Italian prison inmates.

PMID- 17177301
TI  - Molecular epidemiology of human adenovirus isolated from children hospitalized
      with acute respiratory infection in Sao Paulo, Brazil.
AB  - In a study of acute respiratory disease, two collections of nasopharyngeal
      aspirates (NPA) were obtained from children hospitalized at the Pediatric Clinic
      of the University Hospital, Sao Paulo, in 1995 and 2000. Adenovirus was detected
      in 33 (8.2%) of 401 children followed. These viruses were isolated in HEp-2, HEK
      293, or NCI-H292 cells and serotyped by neutralization. The genome types were
      determined after restriction analyses of the genomic DNA extracted from infected
      cells. Nineteen isolates were characterized as Human adenovirus B, genome types
      HAdV-3a, HAdV-7h, and HAdV-7h1; 11 as Human adenovirus C, genome types HAdV-1D10,
      HAdV-2D25, HAdV-5D2, and HAdV-6D3. Our findings show that species C adenoviruses
      present an endemic infection pattern, with co-circulation of different serotypes
      and genome types; no new genomic variant was observed. Species B adenoviruses
      showed epidemic infection patterns, with shifts in the predominant genome type.
      The isolates from 1995 belong to genome type 7h, or the variant 7h1, with a clear
      substitution of the type 7b, prevalent in Sao Paulo for more then 10 years. In
      2000, the variant 7h1 predominated and the emergence of the type 3a was observed.
      Almost 10 years passed between the identification of HAdV-7h in Argentina and its
      detection in Sao Paulo. The geographic isolation of these two countries was
      reduced by the increase in population mobility due to growing commercial
      relationships.

PMID- 17177303
TI  - Seroprevalence of Hepatitis-B infection amongst Taiwanese university students 18
      years following the commencement of a national Hepatitis-B vaccination program.
AB  - In Taiwan, the nation-wide Hepatitis-B virus (HB) vaccination program was first
      launched in July 1984 and was directed to those infants born to hepatitis B
      surface antigen (HBsAg) carrier mothers in Taiwan. From July 1986 onwards, all
      infants born in Taiwan were immunized against HB. This study examined the HB
      infection status amongst students at a Taiwanese university 18 years subsequent
      to the implementation of universal HB vaccination. A total of 1,969 new
      university entrants in 2005 were grouped into 1 of 3 distinct birth cohorts
      according to their HB-vaccination schedule (cohort-1 students born prior to July
      1, 1984; cohort-3 students born subsequent to June 30, 1986) and were examined
      for their serum HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and
      antibody to hepatitis B core antigen (anti-HBc) status. Immunity arising from
      vaccination was defined as an anti-HBs level 10 mIU/ml. We observed a trend
      toward a decreasing anti-HBc-positive rate and a decreasing HBsAg carrier rate
      from, respectively, 26.5 and 8.7% for cohort-1 to 4.7 and 1.7% for cohort-3
      students. The prevalence of students featuring seronegativity for all three HB
      markers increased from 12.3% for cohort-1 to 48.8% for cohort-3 individuals.
      Amongst the 1,695 subjects revealing seronegativity for HBsAg and anti-HBc, their
      anti-HBs level was analyzed according to their birth year. The prevalence of
      students featuring a non-protective anti-HBs level increased from 11.9% for birth
      year 1984 individuals to 48.2% for birth-year 1987 students. The introduction of
      HB vaccine has effectively reduced the transmission of HBV infection in Taiwan,
      18 years subsequent to the commencement of the universal HB-vaccination program.
      A "waning-off" effect of anti-HBs seropositivity acquired from the HB vaccination
      program has also been observed.

PMID- 17177302
TI  - Apoptosis-associated gene expression in HIV-infected patients in response to
      successful antiretroviral therapy.
AB  - The simultaneous expression of 19 apoptosis-related genes was analyzed by RNA
      protection assay in peripheral blood mononuclear cells of HIV-infected patients
      before and during successful antiretroviral therapy (ART). After 12 months of
      therapy, the expression of the pro-apoptotic genes FAS, FAS-L, FAF-1, FADD,
      CASPASE-8, DR3, TRAIL, TNFR-1, TRADD, and BAX was significantly downregulated
      with respect to time 0, while that of BCL-2, BCL-XL, and MCL-1 was significantly
      upregulated. The data suggest that inhibition of cell death in HIV-positive
      patients under successful therapy is the result of a complex network of
      multifactor signaling, correlated with both death and survival of lymphocytes.

PMID- 17177304
TI  - A novel, sensitive, and specific RT-PCR technique for quantitation of hepatitis C
      virus replication.
AB  - The detection of negative-strand hepatitis C virus (HCV) RNA is a hallmark of
      replication. A highly sensitive and specific method is required to quantify the
      very low level of replication inherent to in vitro infection systems. Based on
      reverse transcription with a tagged primer in the 5' non-coding region of the HCV
      genome, followed by a nested PCR with a second round of real-time PCR, a novel
      method is described with improved sensitivity for negative-strand HCV RNA
      quantification. The lower detection level was 25 copies per reaction of negative
      strand HCV RNA, even in the presence of 1 x 10(5) copies of positive-strand HCV
      RNA. This protocol was applied to the detection of negative HCV strand RNA in the
      liver of HCV-infected patients as well as in primary human hepatocytes infected
      in vitro. In both models, and particularly in each of three, independent in vitro
      infection experiments, this assay permitted the quantitation of HCV replication.

PMID- 17177305
TI  - Molecular characterization of human T-cell lymphotropic virus type 2 (HTLV-II)
      from people living in urban areas of Sao Paulo city: evidence of multiple
      subtypes circulation.
AB  - BACKGROUND: In Brazil, human T-cell lymphotropic virus type I and type II (HTLV-I
      and HTLV-II) are co-circulating and possess approximately 65% homology, which
      results in high cross-reactivity in serological tests. Based on the detection of
      EIA and Western blot (WB) tests, HTLV serodiagnosis yields indeterminate results
      in high-risk population, with the true determination of HTLV-II prevalence
      requiring a combined serological and molecular analysis. Molecular analysis of
      HTLV-II isolates has shown the existence of four distinct subtypes: IIa, IIb,
      IIc, and IId. The aim of this study was to evaluate the routine EIA and WB used
      in Sao Paulo city, as well as molecular methods for confirmation of infection and
      HTLV-II subtype distribution. RESULTS: Two hundred ninety-three individuals, who
      were enrolled in the HTLV out-clinic in Sao Paulo city, Brazil, between July 1997
      and May 2003, were tested by EIAs, and positive sera 232 (79%) reactive by one of
      the tests. When these sera were tested by WB revealed 134 were HTLV-I, 28 HTLV
      II, 4 HTLV-I/II, and 48 were indeterminate. Polymerase chain reaction (PCR) on
      the indeterminate group showed that 20 (42%) were HTLV-II and 28 were negative.
      From a total of 48 HTLV-II subjects with DNA available, restriction fragment
      length polymorphism (RFLP) of the env region revealed 47 HTLV-IIa and 1 HTLV-IIb.
      The phylogenetic analysis was performed on 23 samples, which identified 19 as
      subtype a, Brazilian subcluster, and 4 as subtype b. This is the first time HTLV
      II subtype b has been described in Brazil. However, further studies, such as a
      complete nucleotide DNA sequencing, need to be done to confirm these findings.

PMID- 17177306
TI  - Increased prevalence of varicella zoster virus DNA in cerebrospinal fluid from
      patients with multiple sclerosis.
AB  - In order to investigate the possible involvement of viruses in Multiple Sclerosis
      (MS), the study evaluated the presence of viral genomic sequences in
      cerebrospinal fluid (CSF), as markers of viral replication within the central
      nervous system (CNS). A total of 85 CSF samples were collected from 38 MS
      patients, 28 patients with other neurological diseases and 19 subjects without
      neurological diseases. Using nested-PCR, the investigation focused on the
      presence of human herpes virus DNA, including herpes simplex virus 1 (HSV-1) and
      2 (HSV-2), the Epstein-Barr virus (EBV), varicella zoster virus (VZV), human
      cytomegalovirus (HCMV), human herpes virus 6 (HHV-6) and JC virus (JCV). All the
      CSF samples from the individuals without neurological diseases were negative for
      viral DNA. Genomic sequences of HSV-1, HCMV, EBV, HHV6, and JCV were found in
      patients with MS and other neurological diseases without significant differences
      between the two groups. VZV DNA was detected more frequently (P < 0.05) in the MS
      group (31.6%), particularly among the relapsing-remitting MS patients (43.5%),
      compared with patients with other neurological diseases (10.7%). In addition, the
      results indicated that JCV and HHV-6 were replicating actively in the CNS of a
      small, but significant number of patients with MS and other neurological
      diseases. Most importantly, the study revealed a high frequency of VZV DNA in the
      CSF of patients with MS, suggesting a possible role of this virus in the
      pathogenesis of MS.

PMID- 17177307
TI  - Isolation and identification of adenovirus from conjunctival scrapings over a two
      year period (between 2001 and 2003) in Yokohama, Japan.
AB  - Over a 2-year period between 2001 and 2003, a total of 115 conjunctival scrapings
      were collected from patients with keratoconjuctivitis from several hospitals in
      Yokohama, Japan. Out of 115, 94 (82.4%) cases of adenoviruses were detected by
      polymerase chain reaction (PCR); 60 (52.1%) by cell culture isolation; and 16
      (14.0%) by enzyme-linked immunosorbent assay (ELISA). The serotypes were
      determined by PCR- restriction fragment length polymorphism analysis (PCR-RFLP)
      and by the neutralization test (NT). PCR-RFLP was performed using a combination
      of endonucleases such as HhaI, AluI, and HaeIII. Of the 94 PCR-positive samples,
      the serotypes of 91 (96.8%) were identified by PCR-RFLP analysis (adenovirus 3:
      50%, 4: 11%, and 8: 32%). Out of the 115 samples, 60 samples were identified by
      the neutralization (adenovirus 3, 4, 7, and 8). When both PCR-RFLP and the
      neutralization techniques were used, 53.2%, 11.7%, 1.1%, and 34% of the samples
      were identified as adenovirus 3, 4, 7, and 8, respectively. In contrast to the
      results of a nationwide surveillance report, adenovirus 3 was found as a major
      cause of keratoconjunctivitis in the Yokohama area. The nationwide surveillance
      report did not reflect accurately the epidemiological situation in the local
      area. In order to obtain surveillance data that would be useful for the
      prevention of an adenovirus conjunctivitis epidemic, it seems that local
      epidemiology is more important than that nationwide surveillance.

PMID- 17177308
TI  - Efficacy and safety of tenofovir double-dose in treatment-experienced HIV
      infected patients: the TENOPLUS study.
AB  - Drug resistance is an increasing problem in the treatment of HIV infection.
      Tenofovir has been shown to inhibit HIV replication even with thymidine
      associated resistance mutations (TAMs) if they are limited to two or less. Double
      dose of tenofovir disoproxil fumarate (TDF) (600 mg QD) was used to determine
      weather the drug could be virologically effective in patients harbouring HIV
      strains resistant to nucleoside analogues (NRTI). A pilot, open, non-comparative
      add-on study, where patients failing a current antiretroviral regimen, with at
      least two TAMs, and naive for tenofovir, were given tenofovir 600 mg once-daily
      for 4 weeks, in addition to their current failing antiretroviral regimen. The
      primary end-point was the percentage of patients with plasma viral load (VL)
      reduction of at least 0.8 log(10) between baseline and week 4 (W4). Ten patients
      were enrolled. At baseline, the median viral load was 3.66 log(10) copies/ml
      (range 3.13-4.03) and the median CD4 cell count was 407/mm(3) (range 136-1102).
      The percentage of patients with reduction the viral load > or =0.8 log(10) was
      40% at W4. After 4 weeks of treatment with tenofovir 600 mg, the median decrease
      in the viral load was -0.61 log(10) (range -0.05; -0.88) and the median gain of
      CD4 was +109/mm(3). Despite a twofold increase tenofovir plasma concentrations,
      no serious drug-related adverse event were recorded except for one patient
      experiencing an de Fanconi syndrome at week 2. This add-on pilot study supports
      the concept of double dose tenofovir to virologically overcome the decreased
      sensitivity of NRTI-resistant viruses. However, the safety of this regimen needs
      to be considered carefully.

PMID- 17177309
TI  - Chimeric HIV-1 and HIV-2 lentiviral vectors with added safety insurance.
AB  - Lentiviruses are unique in their ability to infect both dividing and non-dividing
      cells. This makes the vectors derived from them particularly useful for gene
      transfer into non-dividing cells, including stem cells. Lentiviral vectors are
      becoming the vectors of choice for si/shRNA delivery. The utility of the
      lentiviral vectors will be enhanced if additional elements of safety are built
      into their design. One safety concern is the generation of replication competent
      virus by recombination. We reasoned that HIV-1 and HIV-2 hybrid or chimeric
      lentiviral vectors will have added safety insurance in this regard. This is based
      on the premise that HIV-1 and HIV-2 are dissimilar enough in sequence to curtail
      recombination, yet similar enough to complement functionally. For hybrid vectors,
      we found that both HIV-1 and HIV-2 transfer vector RNAs could be packaged to
      equivalent titer by the HIV-1 packaging machinery. However, HIV-2 packaging
      machinery was unable to package HIV-1 transfer vector as well as it did HIV-2
      transfer vector. This non-reciprocacity suggested that the requirement for HIV-2
      vectors was more stringent and that for HIV-1 vectors more promiscuous. When the
      HIV-1 transfer vector was packaged with the chimeric packaging construct where
      the leader-gag region of HIV-2 was replaced with that of HIV-1 packaging
      construct, the titer of the vector went up. This suggests that at least some of
      the determinants of specificity for vector assembly reside in the leader-gag
      region. Incorporation of central polypurine tract (cPPT) and woodchuck post
      transcriptional enhance element (WPRE) into the HIV-2 vectors had only modest
      effect on vector titer. Thus, chimeric lentiviral vectors with added safety
      features can be designed without compromising transduction efficiency.

PMID- 17177310
TI  - A new strategy based on recombinant viruses as a tool for assessing drug
      susceptibility of human immunodeficiency virus type 1.
AB  - The emergence of drug-resistant variants during antiretroviral therapy is a
      serious obstacle to sustained suppression of the human immunodeficiency virus
      type 1 (HIV-1). For that reason, resistance assays are essential to guide
      clinicians in the selection of optimal treatment regimens. Genotypic assays are
      less expensive and results are available faster than phenotypic assays. However,
      in heavily experienced patients with multiple treatment failures interpretation
      of complex mutation patterns remains difficult, and in these cases phenotypic
      assays are recommended. This report describes a novel recombinant virus assay
      where protease (PR) and reverse transcriptase (RT) sequences derived from the
      plasma isolated from patients are introduced into the back-bone of an HIV
      molecular clone that expresses Renilla luciferase protein in the place of nef
      gene. All drug resistance profiles analyzed correlate with previously reported
      data and showed high reproducibility. This assay, in addition to a fast
      (completed in 10 days), precise, reproducible and automated method, presents
      several advantages as compared to other phenotypic assays. The system described
      below allows the generation of recombinant viruses with multiples cycles of
      replication carrying a reporter gene in their genomes. These features increase
      the sensitivity of the test, an important aspect to be considered in the
      evaluation of less fit viral isolates. In conclusion, the assay permits the
      quantitation of the level of resistance of clinical HIV-1 isolates to PR and RT
      inhibitors.

PMID- 17177311
TI  - Demography and life history of Thomas langurs (Presbytis thomasi).
AB  - Life history data from wild primate populations are necessary to explain
      variation in primate social systems and explain differences between primates and
      other mammals. Here we report life history data from a 12.5-year study on wild
      Thomas langurs. Mean age at first reproduction was 5.4 years and the sex ratio at
      birth was even. The mean interbirth interval (IBI) after a surviving infant was
      26.8 mo, after nonsurviving infants 17.7 mo, and combined 22.0 mo. Mean annual
      birth rate of adult females was 0.44, while reaching a peak at 6 years of age and
      showing no decrease with age. Mortality was highest during the first year of life
      (48.0% for males and 43.0% for females) and consistently higher for males than
      females. The oldest female observed during the study was estimated to be 20 years
      of age, whereas the oldest male disappeared at age 13 years, indicating that
      males die at a much earlier age than females. A Leslie matrix based on these
      estimates yielded a growth rate of 1.01, which is comparable to the
      nonsignificant increase in density indicated by our long-term field data. A
      comparison with life history data for sympatric frugivorous primates suggests
      that folivory might be associated with faster life history.

PMID- 17177312
TI  - Cortisol response and ovarian hormones in juvenile and cycling female Cebus
      monkeys: effect of stress and dexamethasone.
AB  - We examined cortisol profiles in relation to ovarian hormones and their response
      to a repeated composite stressor with and without dexamethasone suppression. To
      evaluate the day-to-day changes in circulating cortisol relative to ovarian
      hormones, we subjected five adult female Cebus apella monkeys daily to restraint,
      sedation, transport to a neighboring room for femoral venipuncture, and return to
      the cage throughout the menstrual cycle. The cortisol response to the repeated
      stressor for blood collection, its relationship with the ovarian function, and
      the effects of dexamethasone were evaluated in six juveniles (18-24 months old)
      and five adult females in the luteal phase. Blood was sampled at time 0; then the
      monkeys received the vehicle and their blood was sampled again at 1, 2, 4, and 24
      hr. This experiment was repeated 3 weeks later, with dexamethasone (i.m. 2 mg/Kg)
      injected instead of vehicle. Plasma aliquots were assayed for cortisol,
      progesterone, and estradiol. The results revealed that from middle infancy and
      throughout adulthood, hypercortisolism is the norm in female Cebus monkeys. The
      high cortisol values remained unchanged across the cycle despite the cyclic
      changes in estradiol and progesterone levels. Juvenile monkeys exhibited a higher
      cortisol response to stress than adults, and both juvenile and adult monkeys
      exhibited the typical suppression by dexamethasone. A rapid suppression of
      progesterone co-occurred in parallel with cortisol after dexamethasone injection
      in juvenile monkeys, suggesting that most circulating progesterone originates in
      the adrenals. In contrast, adult females exhibited an overincrement of
      progesterone levels, in parallel with a rise in cortisol, in response to the
      stressor, and this effect was exacerbated by dexamethasone. The findings suggest
      that hypercortisolism is insufficient to disrupt ovarian development toward a
      normal cyclical function, and that ovarian steroids have no influence on day-to
      day circulating cortisol levels. On the other hand, the overincrement of
      progesterone levels induced by stress and/or glucocorticoids during the early
      luteal phase is unlikely to interfere with the development of this phase and
      implantation in this monkey species.

PMID- 17177313
TI  - Predicting the frequency of food-related agonism in white-faced capuchin monkeys
      (Cebus capucinus), using a novel focal-tree method.
AB  - Food abundance and distribution have played a central role in the conceptual
      theory of primate socioecology [Janson, Behaviour 105:53-76, 1988; Isbell,
      Behavioral Ecology 2:143-155, 1991; Sterck et al., Behavioral Ecology and
      Sociobiology 41:291-309, 1997; van Schaik, In: Standen V, Foley RA, editors,
      Comparative Socioecology. Oxford: Blackwell. p 195-218, 1989]. This theory
      predicts that agonistic ("contest") competition should occur when food is
      distributed in discrete, defensible patches; in contrast, when food sources are
      distributed uniformly or randomly, non-agonistic ("scramble") competition is
      expected. Primatologists usually measure resource density and patchiness from a
      botanical perspective, ignoring the biology of the animal being studied. Such an
      approach may be irrelevant in terms of how animals view the dispersion of
      resources. Using a novel focal-tree method that measures resource availability on
      a scale that is both spatially and temporally relevant to the animal under
      investigation, we take a cost-benefit approach to predict the frequency of food
      related agonism in white-faced capuchin monkeys (Cebus capucinus) from 11
      ecological and social variables. We retained four variables in the regression
      model: two representing the opportunity for aggression (i.e., feeding bout length
      and the number of feeding adult females), and two representing opportunity costs
      (i.e., fruit abundance and the number of potential feeding sites in the focal
      tree). The results of this study indicate that the amount of food-related
      aggression in white-faced capuchins can be predicted by variables representing
      the costs and benefits of contesting a food resource.

PMID- 17177314
TI  - Mitochondrial DNA variation within and among regional populations of longtail
      macaques (Macaca fascicularis) in relation to other species of the fascicularis
      group of macaques.
AB  - An 835 base pair (bp) fragment of mitochondrial DNA (mtDNA) was sequenced to
      characterize genetic variation within and among 1,053 samples comprising five
      regional populations each of longtail macaques (Macaca fascicularis) and rhesus
      macaques (Macaca mulatta), and one sample each of Japanese (M. fuscata) and
      Taiwanese (M. cyclopis) macaques. The mtDNA haplotypes of longtail macaques
      clustered in two large highly structured clades (Fas1 and Fas2) of a neighbor
      joining tree that were reciprocally monophyletic with respect to those
      representing rhesus macaques, Japanese macaques, and Taiwanese macaques. Both
      clades exhibited haplotypes of Indonesian and Malaysian longtail macaques widely
      dispersed throughout them; however, longtail macaques from Indochina,
      Philippines, and Mauritius each clustered in a separate well-defined clade
      together with one or a few Malaysian and/or Indonesian longtail macaques,
      suggesting origins on the Sunda shelf. Longtail macaques from Malaysia and
      Indonesia were far more genetically diverse, and those from Mauritius were far
      less diverse than any other population studied. Nucleotide diversity between
      mtDNA sequences of longtail macaques from different geographic regions is, in
      some cases, greater than that between Indian and Chinese rhesus macaques.
      Approximately equal amounts of genetic diversity are due to differences among
      animals in the same regional population, different regional populations, and
      different species. A greater proportion of genetic variance was explained by
      interspecies differences when Japanese and Taiwanese macaques were regarded as
      regional populations of rhesus macaques than when they were treated as separate
      species. Rhesus macaques from China were more closely related to both Taiwanese
      and Japanese macaques than to their own conspecifics from India.

PMID- 17177315
TI  - Demographic review of a captive colony of callitrichids (Callithrix kuhlii).
AB  - Although reports on colony demographics for a variety of callitrichid species are
      available in the literature, to date there has not been a detailed examination of
      Wied's black tufted-ear marmoset (Callithrix kuhlii). The purpose of this study
      is to present colony demographics for C. kuhlii from the University of Nebraska
      at Omaha's Callitrichid Research Center from 1991 to 2002. C. kuhlii are
      currently held in a number of zoological parks in the United States and abroad;
      however, the University of Nebraska at Omaha held the only breeding colony in
      North America. Here we report data on lifespan, sex ratio, litter size, and
      interbirth interval (IBI) for that captive breeding colony.

PMID- 17177316
TI  - Use of traps to capture black and gold howlers (Alouatta caraya) on the Islands
      of the upper Parana River, Southern Brazil.
AB  - Howlers (genus Alouatta) are widely captured with the use of anesthetic
      projectiles; however, no capture protocol involving the use of traps has been
      described to date. In the present study we describe the first efficient capture
      program for black and gold howlers (Alouatta caraya) using traps, which was
      implemented on the islands of the upper Parana River in southern Brazil. We
      constructed two trap models with either manual or automatic activation (trap A
      with two entrances and guillotine-type doors; trap B with one entrance and a
      guillotine-type door). The traps were suspended in the canopy by means of
      vertical climbing techniques, and were baited regularly and abundantly with
      bananas and mangoes. We captured 70 howlers (86% using manual activation and 14%
      using automatic activation) on four different islands. We restrained 41 of these
      animals and measured their body mass, which averaged 5.30 kg+/-1.79. Given our
      results, we suggest that the system described in the present study represents an
      alternative capture program for howlers in areas that have low food diversity and
      no other mammal species that will compete for the bait, as has been observed in
      riparian environments, islands, and forest fragments.

PMID- 17177317
TI  - Mouse mutants with neural tube closure defects and their role in understanding
      human neural tube defects.
AB  - BACKGROUND: The number of mouse mutants and strains with neural tube closure
      defects (NTDs) now exceeds 190, including 155 involving known genes, 33 with
      unidentified genes, and eight "multifactorial" strains. METHODS: The emerging
      patterns of mouse NTDs are considered in relation to the unknown genetics of the
      common human NTDs, anencephaly, and spina bifida aperta. RESULTS: Of the 150
      mouse mutants that survive past midgestation, 20% have risk of either exencephaly
      and spina bifida aperta or both, parallel to the majority of human NTDs, whereas
      70% have only exencephaly, 5% have only spina bifida, and 5% have
      craniorachischisis. The primary defect in most mouse NTDs is failure of neural
      fold elevation. Most null mutations (>90%) produce syndromes of multiple affected
      structures with high penetrance in homozygotes, whereas the "multifactorial"
      strains and several null-mutant heterozygotes and mutants with partial gene
      function (hypomorphs) have low-penetrance nonsyndromic NTDs, like the majority of
      human NTDs. The normal functions of the mutated genes are diverse, with clusters
      in pathways of actin function, apoptosis, and chromatin methylation and
      structure. The female excess observed in human anencephaly is found in all mouse
      exencephaly mutants for which gender has been studied. Maternal agents, including
      folate, methionine, inositol, or alternative commercial diets, have specific
      preventative effects in eight mutants and strains. CONCLUSIONS: If the human
      homologs of the mouse NTD mutants contribute to risk of common human NTDs, it
      seems likely to be in multifactorial combinations of hypomorphs and low
      penetrance heterozygotes, as exemplified by mouse digenic mutants and the
      oligogenic SELH/Bc strain.

PMID- 17177318
TI  - Effect of different ventilation modes with FC-77 on pulmonary inflammatory
      reaction in piglets after cardiopulmonary bypass.
AB  - RATIONALE: Cardiopulmonary bypass (CPB) causes pulmonary inflammatory reaction.
      Liquid ventilation with perfluorocarbon has shown an anti-inflammatory effect on
      severely injured lungs. The aim of this study is to investigate the treatment
      effect of different ventilation modes with perfluorocarbon on pulmonary
      inflammatory reaction in piglets after CPB. METHODS: After receiving CPB and
      subsequent infusion of lipopolysaccharide (1 microg/kg), 18 piglets were randomly
      treated with conventional gas ventilation, total liquid ventilation (TLV), or
      partial liquid ventilation (PLV) for 240 min. The lung tissue and blood samples
      were collected at the end of observation period. The pulmonary mRNA expressions
      and plasmatic concentrations of interleukin-6 (IL-6) and interleukin-8 (IL-8)
      were measured. Histological neutrophil count in lung parenchyma was performed.
      RESULTS: Hemodynamics, PaCO2 and PH did not differ among groups during the
      observation period. Both TLV and PLV showed significantly improved oxygenation,
      reduced pulmonary mRNA expressions and plasmatic levels of IL-6 and IL-8, and
      decreased total neutrophil count in lung parenchyma when compared with
      conventional gas ventilation. Furthermore, TLV resulted in significantly better
      oxygenation, lower pulmonary mRNA expressions of IL-6 and IL-8, and less total
      neutrophil count when compared with PLV. CONCLUSION: Both TLV and PLV improved
      oxygenation and reduced pulmonary inflammatory reaction in piglets after CPB,
      whereas TLV is more effective than PLV.

PMID- 17177322
TI  - Medical decisions regarding hormone therapy for menopausal women are
      significantly influenced by the media.

PMID- 17177324
TI  - Use, option and externality values: are contingent valuation studies in health
      care mis-specified?
AB  - A general population sample of Australian respondents completed a contingent
      valuation (CV) survey that asked them to value six scenarios. These varied
      according to whether the scenario was seeking to elicit: (i) use value; (ii)
      externality value; (iii) option value; or (iv) a combination. Results indicate
      that use plus externality and/or option value was significantly greater than use
      value alone. As CV studies in health (care) overwhelmingly focus on use value
      alone - often implicitly through study design rather than explicitly - this
      raises the possibility of mis-specification in CV research in health (care). The
      implications for CV in health (care) are considered.

PMID- 17177323
TI  - Novel glycosylated [Lys(7)]-dermorphin analogues: synthesis, biological activity
      and conformational investigations.
AB  - Syntheses of the [Lys(7)]- and [Hyp(6),Lys(7)]-dermorphin analogues in which
      either Tyr(5) or Hyp(6) are O-glucosylated are described. For comparison, the
      carbohydrate-free peptides have also been prepared. Structural investigations by
      FT-IR and CD measurements were carried out on the synthetic analogues and some
      preliminary pharmacological experiments were also performed. The biological
      potency of the glucosylated analogues was compared with that of the micro-opioid
      receptor agonist dermorphin in GPI preparations. Glucosylation of either Tyr(5)
      or Hyp(6) reduces the potency of both [Lys(7)]-dermorphin and [Hyp(6),Lys(7)]
      dermorphin. The effect induced by the Tyr(5) glucosylation is quite strong and
      the potency of both peptides is reduced by about 150 times. A similar but less
      dramatic effect is induced by the glucosylation of the Hyp(6) residue, and the
      potency of the parent peptide is reduced by about 15 times. The presence of
      acetyl groups on the sugar hydroxyl functions further reduces the agonistic
      potency of the glucosylated analogues. The analgesic potency of [Hyp(6),Lys(7)]-,
      [Hyp(betaGlc)(6),Lys(7)]- and [Tyr(betaGlc)(5),Lys(7)]-dermorphin were also
      tested in vivo by the tail-flick test. The glucosylated hydroxyproline-containing
      analogue is 8-10 times less active than the parent peptide, but its analgesic
      effect lasts significantly longer.

PMID- 17177325
TI  - A kampo medicine, Yin-Chiao-san, prevents bleomycin-induced pulmonary injury in
      rats.
AB  - Yin-Chiao-San (YCS), a kampo medicine, is widely used for patients with pulmonary
      disease and was applied for the treatment of SARS in Asia countries in 2003. For
      this reason, the present study investigated the preventive effect of YCS on
      bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats. Animals were divided
      into four groups: (1) saline control group; (2) BLM-induced group, in which 15
      mg/kg BLM was intraperitoneally injected three times per week for a period of 5
      weeks; (3) BLM + vitamin E (10 mg/kg/day) as a positive group; (4) and BLM + YCS
      (1000 mg/kg/day). After 35 days, the rats were anesthetized, killed and then the
      lungs and bronchoalveolar lavage fluids (BALFs) were collected. The attenuation
      of pulmonary fibrosis was estimated according to the lung index, malondialdehyde
      (MDA), catalase (CAT), hydroxyproline (HP) and tumor necrosis factor-alpha (TNF
      alpha) level in lung tissue and BALF. The serial sections of lung were stained
      with haematoxylin-eosin and Masson trichrome for histopathological observation of
      pulmonary fibrosis. The results indicated that YCS significantly reduced the lung
      index, MDA, HP and TNF-alpha, but YCS significantly enhanced the CAT level when
      compared with the BLM-induced group (p < 0.05). Additionally, the BLM group
      displayed severe histopathological change in the lung tissue, but YCS treatment
      could attenuate the BLM-induced PF. In conclusion, the results demonstrated that
      YCS possesses antioxidant and antiinflammatory activities and also inhibited
      collagen formation. Thus, YCS exhibited a preventive effect in BLM-induced PF and
      it is suggested that YCS may be applied to attenuate the side effects of BLM in
      chemotherapy.

PMID- 17177326
TI  - [Beta-defensin 2: an update].

PMID- 17177327
TI  - [Efficient expression and purification of human beta-defensin-2 in E.coli].
AB  - OBJECTIVE: To demonstrate the possibility of high-level expression of bioactive
      human beta-defensin-2 (hBD2) in E.coli, and to purify the recombinant hBD2.
      METHODS: DNA fragment containing mature hBD2 coding region (smhBD2-cDNA) was
      amplified by PCR, multiple copies of smhBD2-cDNA were linked using Bgl II and
      BamH I enzymes, pET32-nsmHBD2-cDNA with 1, 2, 4, or 8 copies of smhBD2-cDNA was
      constructed. The soluble and insoluble hBD2 proteins were separated and analyzed
      by SDS-PAGE analysis. The soluble protein underwent a separation process
      containing affinity chromatography, enterokinase digestion and ion exchange
      chromatography to get the recombinant hBD2 peptide. The bioactivity of
      recombinant hBD2 was examined by bacteria-inhibition tests in liquid culture.
      RESULT: The plasmids pET32-nsmHBD2-cDNA with 1, 2, 4 copies of smhBD2-cDNA were
      constructed and the expressed soluble protein accounted for 52 %, 48 %, and 31 %
      respectively. The plasmids with 8 copies expressed mainly insoluble protein with
      few in soluble form. The growth of E.coli K12D31 was dramatically suppressed with
      a inhibition rate of 90 %, when the final concentration of recombinant hBD2
      reached between 0.4 to 0.5 mug/ml. CONCLUSION: Fusion expression of human beta
      defensin-2 with multiple joined genes in E.coli could increase the expression of
      hBD2.

PMID- 17177328
TI  - [Construction and expression of recombinant adenovirus expression vector of beta
      defensin-2].
AB  - OBJECTIVE: To explore the possibility of stable expression of cationic peptide
      beta-defensin-2 in eukaryocytes with adenovirus vector. METHODS: The rat beta
      defensin-2 (rBD2) gene was cloned at the downstream of CMV promoter of the
      adenoviral shuttle plasmid pShuttle-CMV. Then pShuttle-CMV-rBD2 was transformed
      into E. coli BJ5183-AD-1, in which recombination occurred between plasmids and
      pAdEasy-1 to construct pAdEasy-rBD2. After confirmation by endonuclease, linear
      pAdEasy-rBD2 was transformed into 292 cells to obtain packaged adenoviral
      expression vector, which was used to infect cos-7 cells and to establish
      respiratory adenovirus infection model of rat. The in vivo and in vitro
      expression activity of recombinant adenovirus was detected by Western blot and
      immunohistochemistry. RESULT: The inserted DNA of pShuttle-CMV-rBD2 consisted of
      rat beta-defensin-2 gene. The pathological effect of infected cells, electronic
      microscopic observation and PCR showed that the recombinant adenovirus vector was
      constructed successfully. The concentration of the adenovirus was 10(9) PFU/ml.
      The vector expressed rat beta-defensin-2 efficiently in vivo and in vitro.
      CONCLUSION: The recombinant adenovirus vector can express cationic peptide beta
      defensin-2 in eukaryocytes.

PMID- 17177329
TI  - [IL-10 inhibits inducible expression pattern of beta-defensin-2 in human
      peripheral blood cells].
AB  - OBJECTIVE: To investigate the effect of IL-10 on the inducibility of human beta
      defensin 2 (hBD-2) in human peripheral blood cells. METHODS: Peripheral blood
      samples were collected from 22 healthy individuals and co-cultured with 0 ng/ml
      lipopolysaccharide (LPS), 100 ng/ml LPS, 10 ng/ml IL-10, or 100 ng/ml LPS plus 10
      ng/ml IL-10 at 37 degree for 6 h. Total RNA was extracted from peripheral blood
      cells and the mRNA level of hBD-2 was detected by relative quantitative real-time
      PCR.. RESULT: No detectable level of hBD-2 mRNA was found in normal peripheral
      blood cells with stimulation of 0 ng/ml LPS or 10 ng/ml IL-10. The mRNA level of
      hBD-2 was increased to 166.9 +/- 35.14 after 100 ng/ml LPS challenge, while the
      mRNA level of hBD-2 was decreased to 30.40 +/- 9.18 after the co-stimulation of
      100 ng/ml LPS plus 10 ng/ml IL-10; which was significantly lower than that with
      LPS alone (P<0.05). CONCLUSION: The expression of hBD-2 gene can be induced by
      LPS.IL-10 inhibits the inducible expression of hBD-2.

PMID- 17177330
TI  - [Effect of recombinant beta-defensin-2 peptide on apoptosis of pulmonary tissue
      in rats with sepsis].
AB  - OBJECTIVE: To investigate the effect of recombinant beta-defensin 2 (BD-2) on the
      apoptosis of pulmonary tissue in rats with sepsis. METHODS: Forty-eight SD rats
      were randomly divided into defensin group and controls. In control group 24 rats
      received 10(7)PFU adenovirus via trachea intubation. In defensin group 24 rats
      received 10(7)PFU recombinant adenovirus carrying all expression cassette of rat
      BD-2 (Ad-rBD2). All rats received cecal ligation and puncture (CLP) to induce
      sepsis 48 h following the administration of adenovirus. Rats of both groups were
      sacrificed at 0, 12, 36 and 72 h after CLP; lungs were removed and fixed for
      Haematoxylin and Eosin (HE) stain. Apoptosis was determined by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) technique.
      RESULT: The apoptosis index (AI) of lung cells increased significantly following
      CLP in control group,while it was significantly lower in defensin group than that
      of control group (P<0.05). In addition, a significant alveolar damage,
      interstitial edema, and infiltration of inflammatory cells were observed in
      control lungs, while it was less severe in defensin group. CONCLUSION:
      Recombinant beta-defensin 2 may reduce the apoptosis of lung cells and attenuate
      lung injury.

PMID- 17177331
TI  - [Protective effect of recombinant beta-defensin-2 on acute lung injury induced by
      sepsis in rats].
AB  - OBJECTIVE: To explore the protective effect of recombinant beta-defensin-2 (BD2)
      on acute lung injury induced by sepsis in rats. METHODS: Recombinant adenovirus
      carrying an expression cassette of rat BD2 (rBD2) or control adenovirus carrying
      empty vector was administered intratracheally to Sprague-Dawley rats 48 h before
      acute lung injury, which was induced by cecal ligation and double puncture (CLP).
      Histological changes of the lungs and 7-day survival rate were determined.
      RESULT: The alveolar damage, interstitial edema, and infiltration of neutrophils
      were reduced and the survival rate was increased significantly in BD2 group than
      those in control group (P < 0.05). The CFU of abdominal bacteria was comparable
      to that in the control rats (P > 0.05). CONCLUSION: The administration of
      recombinant BD2 protects lung injury and improves the survival of rats with
      induced sepsis.

PMID- 17177332
TI  - [Expression of recombinant plasmid of HIV-1 gp120 and IFN-gamma in E. coli and
      its immunoregulatory effect].
AB  - OBJECTIVE: To investigate the regulating effect of interferon-gamma (IFN-gamma)
      gene on the immune response induced by human immunodeficiency virus (HIV) gp120
      in mice. METHODS: The recombinant prokaryotic plasmid pet44b with HIV-1gp120 N
      and pet44b with HIV-1gp120 N linking IFN-gamma were constructed and expressed in
      E. coli BL21 (DE3) through IPTG. The purified proteins gp120 N and gp120 N/IFN
      gamma were used in the following experiments: mice were injected with PBS i. s as
      control group 1, injected i. s with gp120 N as control group 2, and injected i. s
      with gp120 N/IFN-gamma as experiment group. The serum samples and spleen cells
      were collected 2 weeks after completion of immune program.T cells enlargement
      stimulated by gp120, CTL test and the detection of Th1 cytokines (SKs) IL-2, IFN
      gamma and Th2 CKs IL-4, IL-10 were performed. RESULT: SDS-PAGE and Western blot
      confirmed that gp120 N and gp120 N/IFN-gamma fusion proteins were successfully
      expressed. The immune experiments showed that the enlargement of specific T
      lymphocytes, the response of CTL and the expression of Th1 type CKs IL-2 and IL
      gamma against gp120 were significantly different among the three groups (P <
      0.05). And the response of gp120 N/IFN-gamma group was stronger than that of
      gp120 N group, the latter was stronger than that of PBS group (P < 0.05). The
      differences in expression of Th2 type CKs IL-4 and IL-10 were not significant
      among the three groups (P >0.05). CONCLUSION: The cell specific immune responses
      of BALB/c mice to HIV-1CNgp120 antigen can be enhanced when HIV-1CNgp120 gene and
      IFN-gamma gene are used in coordination.

PMID- 17177333
TI  - [Physicochemical characters and gene delivery function of polyethylenimine
      modified with peptide CP9 containing RGD sequence].
AB  - OBJECTIVE: To construct a novel gene delivery vector using polyethylenimine (PEI)
      as backbone modified with the peptide CP9 containing Arginine-Glycine-Aspartic
      acid (RGD) sequence and to verify its physicochemical characters and the gene
      delivery function. METHODS: The chemical linker [N-Succinimidyl-3- (2
      pyridyldithio) ] propionate (SPDP) was employed to bind CP9 onto PEI to form a
      novel gene delivery vector CP9-PEI. The (1)H-NMR and FT-IR were used to verify
      the linkage of CP9. The plasmid DNA condensing ability of CP9-PEI,the shape and
      the particle size of the polyplexes formed with CP9-PEI-plasmid DNA were
      demonstrated by gel retardation assay, electron microscope observation and
      particle size assay,respectively. The enhanced transfection efficiency and the
      integrin targeting capacity were detected by the transfection experiments in
      HepG2 cells and free RGD peptide inhibition test. RESULT: CP9 was linked onto PEI
      successfully. The new synthesized vector CP9-PEI could efficiently condense
      plasmid DNA at N/P ratio of 4 and when N/P ratio was equal to 10, the shape of
      polyplexes formed with CP9-PEI-plasmid DNA was round or round-alike with particle
      size of about 200 nm. The transfection efficiency of CP9-PEI was nearly 2 times
      of PEI in HepG2 cells and the free RGD peptide had the inhibition effect on the
      efficiency of CP9-PEI. CONCLUSION: The modification of CP9 on PEI can improve the
      transfection efficiency of PEI and has the integrin targeting ability.

PMID- 17177335
TI  - [Effects of endogenous histamine on memory impairment induced by
      pentylenetetrazole-kindled epilepsy in rats].
AB  - OBJECTIVE: To investigate the mechanisms of memory impairment induced by
      pentylenetetrazole (PTZ)-kindled epilepsy in rats and the effects of endogenous
      histamine. METHODS: Rats were injected i. p with a subconvulsive dose of PTZ
      every 48 h until fully kindled. Memory was tested by shuttle box with passive
      avoidance. Brain histamine was measured spectrofluorometrically. Neurons of
      hippocampus were investigated with HE stain. RESULT: PTZ-kindled epilepsy caused
      memory impairment in rats, i .e. latency of passive avoidance was shortened in
      shuttle box. Pretreatment of histidine, the precursor of histamine, showed an
      ameliorating effect on memory impairment induced by epilepsy. Decreased histamine
      contents in the hippocampus, thalamus and hypothalamus were observed after fully
      kindled in rat. In addition, intact neurons of the CA1 and CA3 regions in
      hippocampus decreased to 72.7 % and 78.9 % compared with those in control group.
      CONCLUSION: PTZ-kindled epilepsy causes memory impairment, and it might be due to
      a decrease of brain histamine and loss of hippocampal neurons induced by
      epilepsy.

PMID- 17177334
TI  - [Specific suppression of beta-secretase gene expression by short interfering RNA
      in mammalian cells].
AB  - OBJECTIVE: To investigate whether short interfering RNAs(siRNAs) of beta-site APP
      cleaving enzyme (BACE) can inhibit the expression of BACE in mammalian cells.
      METHODS: The gene of EGFP, U6 promoter and beta-secretase targeting siRNA were
      cloned by PCR, respectively. The PCR products were inserted into plasmid pLXSN.
      The interfering vector pLXSN/EGFP-U6-siBACE was transferred into SK-N-SH cells to
      express BACE. The inhibition effect of BACE siRNA on BACE expression was
      investigated by fluoroscopy and immunohistochemistry method. RESULT: The
      interfering vector pLXSN/EGFP-U6-siBACE was constructed successfully. The BACE
      siRNA inhibited the expression of BACE in the SK-N-SH cells specifically and
      effectively, and the production of A beta was reduced. CONCLUSION: BACE siRNA can
      inhibit the expression of BACE gene of mammalian cells.

PMID- 17177336
TI  - [A distinct whole nucleus stain pattern of gamma H2AX induced by N-methyl-No
      nitro-N-nitrosoguanidine].
AB  - OBJECTIVE: To characterize the DNA damage property represented by the distinct
      whole nucleus stain pattern of gammaH2AX induced by N-methyl-No-nitro-N
      nitrosoguanidine (MNNG). METHODS: MNNG-induced gammaH2AX foci formation in human
      amnion FL cells was observed by immunofluorescent microscopy. DNA double-stranded
      breaks (DSBs) were detected by neutral comet assay. General DNA damages were
      detected by alkaline comet assay. RESULT: A distinct whole nucleus stain pattern
      of gammaH2AX was induced by high concentration MNNG (10 mg/L). 1 mg/L MNNG also
      induced this type of stain pattern in a small fraction of cells, although the
      effect was transient. Neutral comet assay did not detect any significant DSBs
      formation in this type of cells, while alkaline comet assay revealed the presence
      of DNA damage. CONCLUSION: Although normal gammaH2AX foci were regarded as a
      biomarker for DSBs, the whole nucleus stain pattern might represent DNA damage
      other than DSBs.

PMID- 17177337
TI  - [Effect of dialysis time in vivo on recovery of amino acids for micro-dialysis
      probe].
AB  - OBJECTIVE: To investigate the variety of vitro recovery of amino acids for
      microdialysis probe after different dialysis time in vivo. METHODS: Probes were
      dialyzed in the amino acids standard solutions with microdialysis system,amino
      acid standard solutions and the microdialysate of probe were detected by the
      method of precolumn derivation with HPLC-RF. RESULT: After using different time
      of probe made by regenerated cellulose membrane, the vitro recoveries of Asp, Glu
      and GABA were not completely same (Asp: F=19.669, P=0.000; Glu: F=103.955,
      P=0.000; GABA: F=3.454, P=0.040); while the vitro recovery of Tau had no obvious
      difference(F=2.001, P=0.152). After using 6 h in vivo, recovery remain percentage
      (RRP) of Asp, Glu,Tau and GABA was 64.34 %, 67.36%, 103.11 % and 98.23 %,
      respectively, the recoveries of Asp, Glu decreased obviously (Asp: P < 0.01,Glu:
      P <0.05). After using 12 h in vivo, the RRP of Asp, Glu, Tau and GABA was 43.44
      %, 24.42%, 77.45 % and 67.36 %, respectively, the recoveries of Asp, Glu and GABA
      decreased obviously (Asp: P < 0.001, Glu: P < 0.001, GABA: P < 0.05). After using
      24 h in vivo, the RRP of Asp, Glu,Tau and GABA was 36.26 %, 12.24 %, 89.48 % and
      71.35 %, respectively, the recoveries of Asp, Glu, GABA decreased obviously (Asp:
      P < 0.0001, Glu: P < 0.0001, GABA: P < 0.01). CONCLUSION: Dialysis in vivo could
      lead to the decline of recovery of probe, the decline is more obvious after
      longer dialysis. So when making brain dialysis experiments, the use time of probe
      should not be too long. To improve the validity of data, some calibration should
      be made on the recoveries of probe.

PMID- 17177338
TI  - [Stimulation by Lycium bararum polysaccharides of the maturation of dendritic
      cells in murine bone marrow].
AB  - OBJECTIVE: To study the effect of Lycium bararum polysaccharides (LBPs)
      stimulation on the maturation of murine bone marrow derived dendritic cells
      (BMDCs). METHODS: Murine bone marrow cells were cultured in GM-CSF and IL-4 for 5
      days, then were purified with a MACS column. Respectively, BMDCs were stimulated
      with LBPs, LPS and RPMI1640 for 2 days. Cell phenotypes and antigens uptake by
      BMDCs were analyzed by flow cytometry. Cytokines released by BMDCs were detected.
      The antigen presenting by BMDCs was evaluated by mixed lymphocyte responses.
      RESULT: Compared with to the BMDCs that only subjected to RPMI 1640, the
      expression of I-A/I-E, CD11c and secretion of IL-12 by BMDCs stimulated with LBPs
      were increased, the phagocytosis of FITC-dextran by BMDCs stimulated with LBPs
      was impaired but the activation of proliferation of allogenic lymphocytes by
      BMDCs was strengthened. CONCLUSION: LBPs promote not only the maturation of
      cultured murine BMDCs in vitro, but also the immune response initiation induced
      by BMDCs.

PMID- 17177340
TI  - [Analysis of blood lead levels of preschool children in Zhejiang Province with
      historical comparison].
AB  - OBJECTIVE: To know the blood lead levels (BLL) of preschool children in Zhejiang
      Province between 1997 to 2003. METHODS: The BLL of preschool children was
      investigated in this province with cluster sampling in 2003, and compared with
      the results with that of 1997. The BLL was determined with graphite oven atom
      absorption spectrography method. RESULT: The average BLL of 2013 preschool
      children in 2003 was (0.34 +/- 0.13) micromol/L, similar with that of 1997 [(0.35
      +/- 0.26)micromol/L (P >0.05)]. There were 274 children with BLL >or= 0.483
      micromol/L, and the rate of lead poisoning was 13.61 %, lower than that of 1997
      (when there were 448 children with BLL >or= 0.483 micromol/L, and the rate of
      lead poisoning was 23.84%). In 2003, the rates of lead poisoning among preschool
      children of Hangzhou, Shangyu, Zhoushan and Changshan were 7.69%, 15.37%, 10.87%
      and 20.15 %, respectively. There were significant differences among the four
      areas (P < 0.01). In comparison with the results of 1997, the lead poisoning
      rates of Hangzhou and Shangyu children decreased significantly, while that of
      Changshan children increased significantly (P <0.01), and that of Zhoushan
      children didn't change significantly. The highest rate of lead poisoning was
      found in children of 4-6 years group as 6 years ago. CONCLUSION: The rate of lead
      poisoning among preschool children has decreased significantly now in Zhejiang
      Province. But the condition of BLL in preschool children is still far from
      optimistic. The environmental lead pollution in remote mountain areas and island
      areas should be highly concerned by the government.

PMID- 17177339
TI  - [Research on relationship between gene polymorphisms of interleukin-1 family and
      endometriosis].
AB  - OBJECTIVE: To investigate whether interleukin-1 beta (IL-1beta ) and interleukin
      1 receptor antagonist (IL-1RA) gene polymorphisms are associated with
      endometriosis (EMs) in Chinese women. METHODS: One hundred and thirty-eight
      patients with EMs and 100 women without EMs were enrolled in the study.
      Polymorphisms for IL-1 beta-511 promoter, IL-1 beta exon 5, and IL-1RA were
      detected by polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP). RESULT: There were no significant differences about the
      distribution of the genotypes and alleles of IL-1 beta -511 promoter and IL-1
      beta exon 5 in two groups (P > 0.05). The frequencies of A1/A1, A1/A2, A1/A4 and
      A2/A2 of IL-1RA gene were 84.1 %, 12.3 %, 2.9 % and 0.7 % in EMs and 95 % , 4 %
      ,1 % and 0 % in controls, respectively (P=0.042). The A1, A2 and A4 alleles were
      91.7 % , 6.9 % and 1.4 % in EMs and 97.5 % , 2 % and 0.5 % in controls (P=0.019).
      In comparison with the reference genotype, the wild A1/A1 homozygote, the odds
      ratio for A1/A2 was 3.48 (95 % CI: 1.13 - 10.69). Compared with the A1 allele,
      the odds ratio for the A2 allele was 3.66 (95 % CI: 1.23 - 10.94). CONCLUSION:
      Association between the IL-1 beta-511 promoter,IL-1 beta exon 5 polymorphisms and
      EMs in China is not found. However, the A2 allele of IL-1RA gene may be one of
      the risk factors for the Chinese women in Zhejiang Province to suffer EMs.

PMID- 17177341
TI  - [Transcatheter closure of perimembranous ventricular septal defects in children
      following transthoracic echocardiography].
AB  - OBJECTIVE: To evaluate the efficacy and safety of transcatheter closure of
      perimembranous ventricular septal defects (VSD) in children following
      transthoracic echocardiography (TTE). METHODS: From September 2002 to December
      2005, eighty-nine children (47 males and 42 females) with perimembranous (VSD)
      underwent an attempt of transcatheter interventional occlusion. Among the 89
      children, one of them was diagnosed with patent ductus arterious (PDA) and six
      with VSD leakage after the surgical repair (three with leakage after the surgical
      repair of tetralogy of Fallot and three with leakage after the surgical repair of
      VSD). The mean age of patients was (6.4 +/- 3.9) years (ranged from 1 to 18
      years). The mean body weight of patients was (22 +/- 11 )kg (ranged from 9 to 78
      kg). The mean diameter of VSD measured by TTE was (4.3 +/- 1.5) mm(ranged from 2
      to 8.5mm). The path of artery to vein was established following X-rays and TTE.
      Occluder was released through the right heart system. All patients were followed
      up in 1, 3, 6 and 12 months after procedure of TTE, X-ray and
      electrocardiography. RESULT: The devices were deployed successfully in 85
      patients, the rate of success was 95.5%. No death occurred during and after the
      procedure. There was trivial residual shunt in 12 patients immediately after the
      closure by TTE and angiography. Twenty-four hours later, only 3 patients had
      trivial residual and no shunt existed after 6 months follow-up. Convulsion
      occurred in 1 case due to serious cardiac arrhythmias. Hemolysis was found in 2
      cases. Other complications included 2 cases of complete left bundle branch block,
      1 cases of left anterior fascicular block and 3 cases of incomplete right bundle
      branch block. They recovered after 3 to 7 days of corticosteroid treatment. After
      1 to 36 months (mean 9 months) follow-up, none of occluders displacement occurred
      and no valve was involved. CONCLUSION: Transcatheter closure of membranous VSD
      using occluder would be safe and effective for children, and the results of short
      term was satisfied. Transcatheter closure of VSD following TTE is a feasible
      method. TTE has the potential benefit of avoiding general anesthesia and
      esophageal intubation in children.

PMID- 17177342
TI  - [Clinical application of biofragmentable anastomosis ring for intestinal
      anastomosis].
AB  - OBJECTIVE: To compare the efficacy of the biofragmentable anastomotic ring (BAR)
      with conventional hand-sutured and stapling techniques,and to evaluate the safety
      and applicability of the BAR in intestinal anastomosis. METHODS: The totol of 498
      patients performed intestinal anastomosis from January 2000 to November 2005 were
      allocated to BAR group (n=186), hand-sutured group (n=177) and linear cutter
      group (n=135). The operative time, postoperative convalescence and corresponding
      complication were recorded. Postoperative anastomotic inflammation and
      anastomotic stenosis were observed during half or one year follow-up of 436
      patients. RESULT: The operative time was (102 +/- 16) min in the BAR group, (121
      +/- 15) min in the hand-sutured group, and (105 +/- 18 ) min in the linear cutter
      group. The difference was significant statistically (P <0.05). The operative time
      in BAR group and linear cutter group was shorter than hand-sutured group. One
      case of anastomotic leakage was noted in the BAR group, one case in the hand
      sutured group, and none in the linear cutter group. They were cured by
      conservative methods. One case of anastomotic obstruction happened in the BAR
      group, one case in the hand-sutured group. Two of them were cured by conservative
      methods. Two cases of anastomotic obstruction happened in the hand-sutured group.
      However, one of them required reoperation to remove the obstruction. In the BAR,
      hand-sutured and the linear cutter group, the postoperative first flatus time was
      (67.2+/- 4.6) h, (70.2 +/- 5.8) h and (69.2 +/- 6.2)h, respectively. No
      significant differences were observed among three groups(P > 0.05). The rate of
      postoperative anastomotic inflammation was 3.0 % (5/164) in the BAR group, 47.8 %
      (76/159) in hand-sutured group and 7.1 % (8/113) in the linear cutter group. The
      difference was significant statistically (P <0.05). The rate of postoperative
      anastomotic inflammation in the BAR group and in the linear cutter group was less
      than that in hand-sutured group. CONCLUSION: BAR is one of rapid,safe and
      effective methods in intestinal anastomosis. It has less anastomotic inflammatory
      reaction than hand-sutured technique. It should be considered equal to manual and
      stapler methods.

PMID- 17177344
TI  - [Role of brain mast cell in multiple sclerosis and Wernicke's encephalopathy].
AB  - OBJECTIVE: Mast cell which is considered to participate in immune response has
      long been studied. However its true role in center nervous system is still
      unknown. Recently,mast cell has been found to play an important function during
      the process of multiple sclerosis and Wernicke's encephalopathy in the brain.
      Multiple sclerosis is an inflammatory demyelinating disease, and Wernicke's
      encephalopathy is caused by deficiency of thiamine. Mast cell deteriorates the
      neuronal damage and the course of diseases by their mediators. Such studies may
      supply new idea on the therapy of these diseases.

PMID- 17177343
TI  - [Advances in pathogenesis of psoriasis].
AB  - OBJECTIVE: The pathogenesis of psoriasis recently made great advancement due to
      the introduction of transgenic mouse model. K14-VEGF transgenic mouse showed many
      of the cellular and molecular features of psoriasis, including angiogenesis in
      dermis, altered epidermal proliferation and differentiation. Psoriasis of early
      onset and severe disease showed significantly increased frequency of the +405CC
      genotype and the C allele. Transgenic mice with keratinocytes expressing active
      Stat3 (K5. Stat3C mice) developed a skin phenotype closely resembling psoriasis.
      Stat 3 may link activated keratinocytes and immunocytes required for development
      of psoriasis. More recently, a novel mouse model with epidermal specific double
      knockout of the c-Jun and JunB genes showed developments of psoriasis-like skin
      phenotype and arthritic lesions. All these data provided more profound
      understanding in pathogenesis and therapy of psoriasis.

PMID- 17177345
TI  - [Stent-assisted percutaneous transluminal angioplasty for intracranial vertebral
      artery stenosis: a reports of two cases].

PMID- 17177346
TI  - Competitive chemisorption between pairs of cinchona alkaloids and related
      compounds from solution onto platinum surfaces.
AB  - Quinoline-derived compounds exhibit the following relative chemisorption
      strengths from CCl4 solutions onto platinum surfaces, as determined by in-situ
      infrared spectroscopy: quinine, quinidine > cinchonidine > cinchonine > 6
      methoxyquinoline > lepidine > quinoline. This sequence explains nonlinear
      enantioselectivity effects with cinchona chiral modifiers in hydrogenation
      catalysis.

PMID- 17177348
TI  - High-performance low-cost organic field-effect transistors with chemically
      modified bottom electrodes.
AB  - The characteristics of organic field-effect transistors (OFETs) were dramatically
      improved by chemically modifying the surface of the bottom-contact Ag or Cu
      source-drain (D-S) electrodes with a simple solution method. The contact
      resistance and energetic mismatch typically observed with Ag D-S electrodes in
      pentacene bottom-contact OFETs can be properly eliminated when modified by the Ag
      TCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane). The pentacene transistors with
      low-cost Ag-TCNQ-modified Ag bottom-contact electrodes exhibit outstanding
      electrical properties, which are comparable with that of the Au top-contact
      devices. It thus provides a novel way toward high-performance low-cost bottom
      contact OFETs.

PMID- 17177347
TI  - TCNQ dianion-based coordination polymer whose open framework shows charge
      transfer type guest inclusion.
AB  - A three-dimensional coordination framework constructed with 7,7,8,8-tetracyano-p
      quinodimethane (TCNQ) diainon has been synthesized and structurally
      characterized. This open framework possessing a highly electron-rich surface has
      an optical sensing cavity for several aromatics with crystal-to-crystal
      transformation and strong accommodation, which are based on a charge-transfer
      interaction with them.

PMID- 17177349
TI  - The in vitro characterization of the iterative avermectin glycosyltransferase
      AveBI reveals reaction reversibility and sugar nucleotide flexibility.
AB  - The glycosyltransferase AveBI, which is involved in the biosynthesis of the
      macrolide antihelmintic avermectin (AVM), was characterized in vitro. AveBI was
      confirmed to catalyze two separate iterative additions of l-oleandrose, and the
      reversibility of AveBI-catalyzed reaction was also demonstrated. Investigation of
      sugar nucleotide specificity revealed 10 unique sugar nucleotide substrates
      which, in combination with five distinct aglycones, led to the production of 50
      differentially glycosylated AVM variants.

PMID- 17177350
TI  - Enantioselective synthesis of an all-syn four vicinal fluorine motif.
AB  - Alkanes bearing multiple vicinal fluorine atoms at adjacent stereocenters may be
      considered intermediate between alkanes and perfluoroalkanes, and as a class,
      their chemistry and behavior remain to be explored. We report here a
      stereoselective synthesis of an all-syn four vicinal fluorine motif as a single
      enantiomer. The four vicinal fluorine compound was amenable to single-crystal X
      ray analysis, and the resulting structure displays gauche relationships between
      all four fluorines, consistent with the fluorine gauche effect, and CF...HC
      hydrogen bonding between adjacent fluoroalkyl chains.

PMID- 17177351
TI  - Mechanisms of electron transfer in catalysis by copper zinc superoxide dismutase.
AB  - Activated oxygen intermediates during copper zinc superoxide dismutase (SOD)
      catalysis were investigated using an isotope fractionation technique and natural
      abundance reagents. Competitive oxygen kinetic isotope effects (KIEs) are
      reported for the enzyme-catalyzed disproportionation of superoxide as well as the
      stoichiometric reaction of reduced SOD with molecular oxygen. Analysis within the
      context of quantum mechanical electron transfer theory provides evidence against
      an outer-sphere mechanism for O2*- oxidation. A CuII-O2-I intermediate is,
      therefore, proposed. The SOD-catalyzed oxidation of O2*- is characterized by an
      inverse (<1) KIE which is similar to those determined for the analogous reactions
      of synthetic copper compounds. An inverse kinetic isotope effect upon the
      enzymatic reduction of O2*- is also observed and proposed to arise from rate
      determining proton transfer which leads to the formation of HO2* in the SOD
      active site.

PMID- 17177352
TI  - Stepwise synthesis and magnetic control of trimetallic magnets
      [Co2Ln(L)2(H2O)4][Cr(CN)6].nH2O (Ln = La, Gd; H2L = 2,6-Di(acetoacetyl)pyridine)
      with 3-D pillared-layer structure.
AB  - Integration of mononuclear [Cr(CN)6]3- and preorganized trinuclear [Co2Ln(L)2]3+
      complexes provides novel trimetallic magnets having a 3-D pillared-layer
      framework with an alternate array of 2-D layer extended by Cr(III)-CN-Co(II)
      linkages and Ln(III) ion. The overall magnetic nature can be systematically
      controlled by Ln(III) ions inserted between the 2-D ferromagnetic layers.

PMID- 17177353
TI  - Coexistence of magnetization relaxation and dielectric relaxation in a single
      chain magnet.
AB  - A novel single-chain magnet, [MnIII3O(Meppz)3(EtOH)4(OAc)] (1), has been
      successfully synthesized from a secondary building block
      [MnIII3O(Meppz)3(EtOH)5Cl] (2) with an S = 1 ground state. SCM 1 exhibits both
      magnetization relaxation and dielectric relaxation properties.

PMID- 17177354
TI  - Single-molecule detection of airborne singlet oxygen.
AB  - Airborne singlet oxygen (1O2) molecules, which are generated during the TiO2
      photocatalytic reactions and diffused from the surface into air, were detected at
      the opposite surface using terrylenediimide (TDI) molecules at the single
      molecule level. The novel 1O2 nanosensor, which has a detectable number of about
      1000 1O2 molecules in 70 x 70 square micrometers, can easily detect the single
      1O2 molecule at a distance of over 1000 micrometers from the place of its
      creation in ambient air.

PMID- 17177355
TI  - Radically different antioxidants: thermally generated carbon-centered radicals as
      chain-breaking antioxidants.
AB  - A new class of thermally activated chain-breaking antioxidants is presented.
      Dimers of persistent carbon-centered radicals are able to inhibit the
      autoxidation of cumene and styrene with better rate constants than the commercial
      antioxidant Irganox HP-136 and 3,5-di-tert-butyl-4-hydroxyanisole. A dramatic
      increase in antioxidant activity is observed with increasing temperature as more
      dimers dissociate to their corresponding persistent radicals.

PMID- 17177356
TI  - A "molecular pivot-hinge" based on the pH-regulated intramolecular switching of
      Pt-Pt and pi-pi interactions.
AB  - The binuclear cycloplatinated complex {[Pt(L)]2(mu-dppm)}2+ (1), where HL is a
      new cyclometalating ligand 2-phenyl-6-(1H-pyrazol-3-yl)pyridine, is found to
      behave as a molecular pivot-hinge in which the closing and opening of the hinge
      is effected by the reversible formation and cleavage of the Pt-Pt d8-d8
      interaction and the intramolecular pi-pi interaction mediated by the
      protonation/deprotonation of the 1-pyrazolyl-NH on the cyclometalating ligand L.

PMID- 17177357
TI  - Cooperative Jahn-Teller distortion, phase transitions, and weak ferromagnetism in
      the KCrF3 perovskite.
AB  - At ambient conditions, the ternary fluoride with formula KCrF3 adopts a
      perovskite-type structure and incorporates the Jahn-Teller active Cr2+ (d4) whose
      electronic configuration and magnetic response are analogous to those of Mn3+
      (d4) and Cu2+ (d9). These ingredients make it an attractive system to study owing
      to the striking similarities with LaMnO3 and the expected strong interplay
      between spin, orbital, and structural ordering phenomena. Indeed, probing the
      properties of KCrF3 as a function of temperature (5 < T < 300 K) has revealed a
      structurally and magnetically far richer phase diagram than hitherto supposed. We
      found that KCrF3 exhibits large cooperative Jahn-Teller distortions which are
      driven by orbital ordering, a series of temperature induced complex structural
      transitions, and weak ferromagnetism which is reminiscent of what is observed in
      LaMnO3.

PMID- 17177358
TI  - Key role of the Lewis base position in asymmetric bifunctional catalysis: design
      and evaluation of a new ligand for chiral polymetallic catalysts.
AB  - New chiral ligands for asymmetric polymetallic catalysts were designed on the
      basis of the assumption that the higher-order assembly structure is stabilized by
      modifying the modular unit. The designed ligands 6 and 7 contained a scaffolding
      cyclohexane ring with a Lewis base phosphine oxide directly attached to the
      scaffold. A module in the polymetallic complex contains two metals per ligand,
      and a stable 6-, 5-, 5-membered fused chelation ring system should be generated.
      Synthesis of these ligands is simple and high yielding, using a catalytic dynamic
      kinetic resolution promoted by the Trost catalyst as a key step. Ligand function
      was assessed in a catalytic asymmetric ring-opening reaction of meso-aziridines
      with TMSCN, a useful reaction for the synthesis of optically active beta-amino
      acids. The Gd complex generated from Gd(OiPr)3 and the ligand was a highly active
      and enantioselective catalyst in this reaction. Enantioselectivity was reversed
      compared to the previously reported d-glucose-derived catalyst containing the
      same chirality of the individual module. ESI-MS analysis and X-ray
      crystallographic studies indicate that the assembly state of the modules in the
      polymetallic catalysts differs depending on the chiral ligand. The difference in
      the higher-order structure stems from a subtle change (one carbon) in the
      position of the Lewis base relative to the Gd metal. The change in the higher
      order structure of the polymetallic complex led to a dramatic reversal of the
      enantioselectivity and increased catalyst activity.

PMID- 17177359
TI  - The total synthesis of (+/-)-11-O-debenzoyltashironin.
AB  - The total synthesis of the putative non-peptidyl neurotrophic factor 11-O
      debenzoyltashironin has been accomplished. The key transformation involves a
      biomimetic oxidative dearomatization/transannular Diels-Alder sequence that
      closes the tetracyclic carbon skeleton present in the natural product.

PMID- 17177360
TI  - An activated equivalent of lactide toward organocatalytic ring-opening
      polymerization.
AB  - The alpha-lactone equivalent lacOCA exhibits remarkable reactivity compared with
      lactide in nucleophile-catalyzed ROP. PLAs of controlled molecular weights and
      narrow polydispersities are typically obtained under mild conditions using DMAP
      and various protic initiators.

PMID- 17177362
TI  - Ultrafast spectroscopic study of the photochemistry and photophysics of
      arylhalodiazirines: direct observation of carbene and zwitterion formation.
AB  - Ultrafast photolysis (lambdaex = 270, 350, or 360 nm) of bromophenyl,
      chlorophenyl, fluorophenyl, and fluoro-para-trifluoromethylphenyl diazirines
      produces transient species which absorb broadly in the UV and visible regions.
      Transient decay can be fit to either mono- or biexponential functions (tau1
      approximately 0.3-10 ps, tau2 approximately 10-350 ps; dependent on solvent and
      halogen). Fluoro- and chlorophenylcarbene are formed within the time resolution
      of the spectrometer (300 fs, 270 nm excitation). Bromophenyl diazirine decay (270
      nm excitation) correlates with the growth of bromophenylcarbene. Solvent and
      substituent effects on the slower decays of the transient absorptions are
      consistent with assigning the carriers of transient absorption in the visible
      region to ring-opened zwitterionic species.

PMID- 17177361
TI  - An antiparallel alpha-helical coiled-coil model system for rapid assessment of
      side-chain recognition at the hydrophobic interface.
AB  - Both parallel and antiparallel alpha-helical coiled-coil dimers are common among
      proteins; however, biophysical scrutiny has focused almost entirely on parallel
      dimers. We describe the development of a model system that enables efficient and
      systematic analysis of hydrophobic packing between antiparallel alpha-helices.
      Our findings reveal significant differences in packing preferences between
      parallel and antiparallel coiled-coils.

PMID- 17177363
TI  - Enantioselective reductive coupling of 1,3-enynes to heterocyclic aromatic
      aldehydes and ketones via rhodium-catalyzed asymmetric hydrogenation: mechanistic
      insight into the role of Bronsted acid additives.
AB  - Hydrogenation of 1,3-enynes 1a-e in the presence of heterocyclic aromatic
      aldehydes and ketones using chirally modified cationic rhodium precatalysts
      results in reductive coupling to afford dienylated alpha-hydroxy heteroarenes 2
      23 with exceptional levels of regio- and enantiocontrol. Coupling of enyne 1a to
      2-pyridinecarboxaldehyde using an achiral rhodium catalyst in the presence of a
      chiral Akiyama-Terada-type phosphoric acid derived from BINOL as the Bronsted
      acid co-catalyst provides the coupling product 2 with substantial levels of
      optical enrichment (82% ee). This result suggests that substrate protonation
      and/or formation of a strong hydrogen bond occurs in advance of the stereogenic C
      C bond forming event. Further, the high levels of asymmetric induction
      demonstrate that interaction of the aldehyde with the Bronsted acid activates the
      system toward C-C coupling. Reductive coupling of enyne 1a and 2
      pyridinecarboxaldehyde under an atmosphere of elemental deuterium provides the
      monodeuterated product deuterio-2, consistent with a catalytic mechanism
      involving alkyne-carbonyl oxidative coupling followed by hydrogenolytic cleavage
      of the resulting oxametallacycle. The diene side chain of the coupling products
      is subject to diverse selective transformations, as demonstrated by the
      conversion of coupling products 2 and 8 to compounds 24-26 and 27-29,
      respectively.

PMID- 17177364
TI  - Synthesis and reactivity of the methylene arenium form of a benzyl cation,
      stabilized by complexation.
AB  - Benzyl cations are unstable intermediates involved in various chemical and
      biological processes. Two extreme resonance forms of these cations include
      positive charge localization at the methylene carbon or delocalization in the
      ring, the latter, nonaromatic form, termed "methylene arenium". The preparation
      of the discrete methylene arenium compound, stabilized by coordination to a metal
      (palladium) center, is described. It was fully characterized, including by X-ray
      diffraction. Reactivity patterns, resulting from charge distribution in the ring,
      were observed. Upon controlled release of the methylene arenium compound into
      solution, it demonstrates aromatic benzyl cation reactivity.

PMID- 17177365
TI  - The two-state issue in the mixed-valence binuclear CuA center in cytochrome C
      oxidase and N2O reductase.
AB  - For the CuA site in the protein, sigmau* and piu are the ground and lowest energy
      excited-states, respectively. EPR data on CuA proteins show a low g parallel
      value of 2.19 which derives from spin-orbital coupling between sigmau* and piu
      which requires an energy gap between sigmau* and piu of 3000-4500 cm-1. On the
      other hand, from paramagnetic NMR studies, it has been observed that the first
      excited-state is thermally accessible and the energy gap between the ground state
      and the thermally accessible state is approximately 350 cm-1. This study
      addressed this apparent discrepancy and evaluated the roles of the two electronic
      states, sigmau* and piu, in electron transfer (ET) of CuA. The potential energy
      surface calculations show that both NMR and EPR results are consistent with the
      electronic/geometric structure of CuA. The anti-Curie behavior observed in
      paramagnetic NMR studies of CuA results from the thermal equilibrium between the
      sigmau* and piu states which are at very close energies in their respective
      equilibrium geometries. Alternatively, the EPR g-value analysis involves the
      sigmau* ground state in the geometry with a short dCu-Cu where the piu state is a
      Frank-Condon excited-state with the energy of 3200 cm-1. The protein environment
      plays a role in maintaining CuA in the sigmau* state as a lowest-energy state
      with the lowest reorganization energy and high-covalent coupling to the Cys and
      His ligands for efficient intra- and intermolecular ET with a low-driving force.

PMID- 17177366
TI  - Remote desymmetrization at near-nanometer group separation catalyzed by a
      miniaturized enzyme mimic.
AB  - The chirality of biological receptors often requires syntheses of therapeutic
      compounds in single enantiomer form. The field of asymmetric catalysis addresses
      enantioselective synthesis with chiral catalysts. Chemical differentiation of
      sites within molecules that are separated in space by long distances presents
      special challenges to chiral catalysts. As the distance between enantiotopic
      sites increases within a substrate, so too may the requirements for size and
      complexity for the catalyst. The extreme of catalyst complexity could be defined
      by macromolecular enzymes and their amazing capacity to effect stereospecific
      reactions over long distances between reactive sites and enzyme-substrate
      contacts. We report here a synthetic, miniaturized enzyme mimic that catalyzes a
      desymmetrization reaction over a very long distance.

PMID- 17177368
TI  - The sodium salt of diethyl 1H-pyrazole-3,5-dicarboxylate as an efficient
      amphiphilic receptor for dopamine and amphetamines. crystal structure and
      solution studies.
AB  - The sodium salt of the diethyl 1H-pyrazole-3,5-dicarboxylate (2) of amphiphilic
      character is able to interact with (+)-amphetamine, (+)-methamphetamine, and
      dopamine, yielding stable complexes. Crystal structure of 2 with (+)-amphetamine
      leads to a very nice double helical supramolecular structure.

PMID- 17177367
TI  - PNA-DNA duplexes, triplexes, and quadruplexes are stabilized with trans
      cyclopentane units.
AB  - Peptide nucleic acids (PNAs) are non-natural nucleic acid mimics that bind to
      complementary DNA and RNA with high affinity and selectivity. PNA can bind to
      nucleic acids in a number of different ways. Currently, the formation of PNA
      oligonucleotide duplex, triplex, and quadruplex structures have been reported.
      PNAs have been used in numerous biomedicial applications, but there are few
      strategies to predictably improve the binding properties of PNAs by backbone
      modification. We have been studying the benefits of incorporating (S,S)-trans
      cyclopentane diamine units (tcyp) into the PNA backbone. In this Communication,
      we report the improvement in stability associated with tcyp incorporation into
      PNA-DNA duplexes, triplexes, and quadruplexes. The broad utility of this
      modification across multiple types of PNA structures is unique and should prove
      useful in the development of applications that rely on PNA.

PMID- 17177369
TI  - Encapsulation and NMR on an aggregating peptide before fibrillogenesis.
AB  - The early stages of peptide and protein aggregation include the formation of
      soluble oligomers, some of which may be cytotoxic. There is a paucity of
      structural information on these oligomers, however, because they are temporally
      unstable and tend to aggregate further into insoluble protofibrils and fibrils.
      To obtain structural information on soluble oligomers, we have developed a
      procedure for encapsulating a fibril-forming peptide, Peptide 1 (NH2
      SDDYYYGFGSNKFGRPRDD-COOH), in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      single bilayer vesicles (POPC SBVs). We also encapsulated a non-fibril forming
      peptide, Peptide 2 (NH2-EEWEE-COOH), in POPC SBVs. The nominal concentration of
      Peptide 1 in the resulting 40 nm diameter SBVs was 2.4 +/- 0.1 mM, well above the
      concentration at which Peptide 1 forms fibrils. We demonstrated that these
      peptides had indeed been encapsulated by measuring longitudinal relaxation times
      (T1) in the presence and absence of a paramagnetic substance, 1 mM Gd-EDTA, by
      NMR spectroscopy. When the peptides were free in solution, they showed the
      expected shortening of T1 times and broadening of NMR peaks. In contrast, peptide
      encapsulated in POPC SBVs were shielded from the effects of Gd-EDTA and showed
      preservation of T1 values and NMR line widths. To demonstrate that encapsulation
      inhibits fibril formation, we measured one-dimensional proton (1D-1H) NMR spectra
      of the peptides in solution, and of the encapsulated peptides immediately after
      encapsulation, and 4 days after encapsulation, because Peptide 1 forms fibrils
      within 1 day. A 2.8 mM solution of Peptide 1 shows the loss of NMR signal
      expected for a fibrillizing peptide. In contrast, the 1D-1H spectra of
      encapsulated Peptide 1 measured immediately after encapsulation and 4 days after
      encapsulation were essentially identical, with preservation of line width at 4
      days, i.e., well within the time frame of most high-resolution NMR experiments.
      Encapsulation may provide a means to obtain high-resolution NMR data on unstable
      soluble oligomers of peptides implicated in amyloidoses such as Alzheimer's
      Disease and provide the first detailed structural information about these
      possibly cytotoxic species that have hitherto been inaccessible to analysis.

PMID- 17177370
TI  - A renewable nanosensor based on a glass nanopipette.
AB  - A fluorescent nanosensor based on reporter dye molecules trapped in the tip of a
      nanopipette has been developed. This 100 nm sized nanosensor has been shown to be
      capable of measuring local pH and mapping sodium concentration with a temporal
      resolution of a few milliseconds.

PMID- 17177371
TI  - Synthesis and biological activity of PTEN-resistant analogues of
      phosphatidylinositol 3,4,5-trisphosphate.
AB  - The activation of phosphatidylinositol 3-kinase (PI 3-K) and subsequent
      production of PtdIns(3,4,5)P3 launches a signal transduction cascade that
      impinges on a plethora of downstream effects on cell physiology. Control of PI 3
      K and PtdIns(3,4,5)P3 levels is an important therapeutic target in treatments for
      allergy, inflammation, cardiovascular, and malignant human diseases. We designed
      metabolically stabilized, that is, phosphatase resistant, analogues of
      PtdIns(3,4,5)P3 as probes for long-lived potential agonists or potential
      antagonists for cellular events mediated by PtdIns(3,4,5)P3. In particular, two
      types of analogues were prepared containing phosphomimetics that would be
      selectively resistant to the lipid 3-phosphatase PTEN. The total asymmetric
      synthesis of the 3-phosphorothioate-PtdIns(3,4,5)P3 and 3-methylenephosphonate
      PtdIns(3,4,5)P3 analogues is described. These two analogues showed differential
      binding to PtdIns(3,4,5)P3 binding modules, and both were potential long-lived
      activators that mimicked insulin action in sodium transport in A6 cells.

PMID- 17177372
TI  - Self-assembling poly(dioxaborole)s as blue-emissive materials.
AB  - Conjugated, borole-linked polymers have been self-assembled based on boronate
      ester formation between a fluorene-2,7-diboronic acid and 1,2,4,5
      tetrahydroxybenzene. Readily soluble polymers with molecular weights approaching
      60 000 have been generated with materials exhibiting extended conjugation over
      approximately 3-5 borole linkages. Emission from these polymers reaches into the
      visible (blue) range, representing a novel class of blue-emitting materials.

PMID- 17177373
TI  - Engineered growth of organic crystalline films using liquid crystal solvents.
AB  - Thin films of organic molecular crystals have drawn widespread attention for
      their scientifically interesting and potentially useful electronic, photonic, and
      chemical properties. However, because their properties are extremely sensitive to
      structural imperfections, domain size, and crystallographic orientation,
      preparation of high-quality thin films with controlled microstructural
      organization under technologically favorable conditions has long been a
      bottleneck toward practical applications and better controlled fundamental
      studies. Here a technique is introduced combining atmospheric pressure vapor
      phase deposition with solution-phase growth in a thin layer of thermotropic
      liquid crystal solvent. The method produces relatively large crystals, enables
      control over crystallographic orientation and growth habit, and involves mild
      processing conditions compatible with a variety of substrates and organic
      materials. Results are presented for the organic semiconductor tetracene, along
      with a discussion of film growth and alignment mechanisms.

PMID- 17177374
TI  - Inorganic-organic hybrid membranes with anhydrous proton conduction prepared from
      3-aminopropyltriethoxysilane and sulfuric acid by the sol-gel method.
AB  - Inorganic-organic hybrid membranes with anhydrous proton conduction were prepared
      from 3-aminopropyltriethoxysilane and H2SO4 by the sol-gel method. The membrane
      has a unique structure: a hexagonal phase formed by the stacking of rodlike
      polysiloxanes with ion complexes of ammonium groups and HSO4- extruded outside.
      The membranes showed high conductivity of 2 x 10-3 S cm-1 at 200 degrees C under
      dry atmosphere. In the membrane, protons probably migrate through the outside of
      the rodlike polysiloxanes along hydrogen-bond chains formed among HSO4- anions.

PMID- 17177375
TI  - Chiral photocages based on phthalimide photochemistry.
AB  - A new class of photoremovable protecting groups, based on a photoinduced
      decarboxylation reaction coupled with the elimination of the caged molecule, is
      described for 2-phthalimido-3-hydroxy-propionate derivatives. When derived from
      enantiopure N-phthaloyl- serine or threonine, the chirality of the starting amino
      acid is transmitted to the protected (caged) molecule. These photocages possess
      good properties for their use in biological systems, and the introduction of
      chirality opens new possibilities for the study of diastereoselective
      photochemistry and stereodifferentiation processes involving the release of the
      caged molecule.

PMID- 17177376
TI  - A mesoporous metal-organic framework with permanent porosity.
AB  - A mesoporous metal-organic framework possessing permanent porosity has been
      synthesized and characterized for the first time.

PMID- 17177377
TI  - Optical imaging of bacterial infection in living mice using a fluorescent near
      infrared molecular probe.
AB  - An optical imaging probe was synthesized by attaching a near-infrared
      carbocyanine fluorophore to an affinity group containing two zinc(II)
      dipicolylamine (Zn-DPA) units. The probe has a strong and selective affinity for
      the surfaces of bacteria, and it was used to image infections of Gram-positive S.
      aureus and Gram-negative E. coli bacteria in living nude mice. After intravenous
      injection, the probe selectively accumulates at the sites of localized bacterial
      infections in the thigh muscles of the mice.

PMID- 17177378
TI  - Peptide macrocyclization: the reductase of the nostocyclopeptide synthetase
      triggers the self-assembly of a macrocyclic imine.
AB  - Many biologically active natural products have macrocyclic structures. In
      nonribosomal peptides macrocyclization is commonly achieved via the formation of
      intramolecular ester or amide bond catalyzed by thioesterase domains during
      biosynthesis. A unique and so far unknown type of peptide cyclization occurs in
      the nostocyclopeptide, a macrocyclic imine produced by the terrestrial
      cyanobacterium Nostoc sp. ATCC53789. In this work we show that a C-terminal
      reductase domain of the nostocyclopeptide nonribosomal peptide synthetase
      catalyzes the reductive release of a linear peptide aldehyde and thereby triggers
      the spontaneous formation of a stable imino head-to-tail linkage. This type of
      molecular self-assembly induced by the reductive release of reactive aldehydes
      may be more commonplace in other complex nonribosomal peptides than originally
      thought.

PMID- 17177379
TI  - A Sakurai-Prins-Ritter sequence for the three-component diastereoselective
      synthesis of 4-amino tetrahydropyrans.
AB  - A simple one-pot procedure for the Sakurai-Prins-Ritter sequence allows rapid
      assembly of 4-acylamino-2,6-substituted tetrahydropyrans in high yields and with
      excellent diastereoselectivity from readily available 4-acetoxy-1,3-dioxanes,
      allylsilanes, and nitriles. A variety of nitriles have been shown to participate.
      Diastereoselectivities are uniformly high and observed stereochemistry of cation
      trapping proceeds according to Alder's model of the 4-tetrahydropyranyl cation.

PMID- 17177381
TI  - GlcNAcstatin: a picomolar, selective O-GlcNAcase inhibitor that modulates
      intracellular O-glcNAcylation levels.
AB  - Many phosphorylation signal transduction pathways in the eukaryotic cell are
      modulated by posttranslational modification of specific serines/threonines with N
      acetylglucosamine (O-GlcNAc). Levels of O-GlcNAc on key proteins regulate
      biological processes as diverse as the cell cycle, insulin signaling, and protein
      degradation. The two enzymes involved in this dynamic and abundant modification
      are the O-GlcNAc transferase and O-GlcNAcase. Structural data have recently
      revealed that the O-GlcNAcase possesses an active site with significant
      structural similarity to that of the human lysosomal hexosaminidases HexA/HexB.
      PUGNAc, an O-GlcNAcase inhibitor widely used to raise levels of O-GlcNAc in human
      cell lines, also inhibits these hexosaminidases. Here, we have exploited recent
      structural information of an O-GlcNAcase-PUGNAc complex to design and synthesize
      a glucoimidazole-based inhibitor, GlcNAcstatin, which is a 5 pM competitive
      inhibitor of enzymes of the O-GlcNAcase family, shows 100000-fold selectivity
      over HexA/B, and binds to the O-GlcNAcase active site by mimicking the transition
      state as revealed by X-ray crystallography. This compound is able to raise O
      GlcNAc levels in human HEK 293 and SH-SY5Y neuroblastoma cell lines and thus
      provides a novel, potent tool for the study of the role of O-GlcNAc in
      intracellular signal transduction pathways.

PMID- 17177382
TI  - Using triethynylphosphine ligands bearing bulky end caps to create a holey
      catalytic environment: application to gold(I)-catalyzed alkyne cyclizations.
AB  - The synthesis, properties and catalytic uses of phosphinoalkynes bearing bulky
      end caps at the alkyne termini, that is, tris[(triarylsilyl)ethynyl]phosphines
      are reported. The most salient feature of the new phosphines is the holey
      molecular shape possessing a deep and large-scale metal-binding cavity. The holey
      phosphines displayed remarkable rate enhancement in the gold(I)-catalyzed six-
      and seven-membered ring forming cyclizations of acetylenic keto esters and 1,7
      enynes. It is proposed that the cavity in the ligand forces a nucleophilic center
      (enol or alkene) of the acetylenic compounds close to the gold-bound alkyne,
      making ring-closing anti attack feasible.

PMID- 17177380
TI  - Catalytic enantioselective hetero-Diels-Alder reactions of an azo compound.
AB  - This communication describes studies in which an azo hetero-Diels-Alder adduct
      was furnished in high regio- and enantioselectivity using azopyridine as a
      reagent and silver as a catalyst. The obtained hetero-Diels-Alder adduct was
      easily converted to the corresponding chiral 1,4-diamino alcohol.

PMID- 17177383
TI  - Lewis acid-catalyzed enantioselective hydroxylation reactions of oxindoles and
      beta-keto esters using DBFOX ligand.
AB  - The first catalytic enantioselective hydroxylation reaction of both 3-aryl and 3
      alkyl-2-oxindoles using the DBFOX-Zn(II) complex, leading to pharmaceutically
      important chiral 3-hydroxy-2-oxindoles was described. The structure of oxidant
      was found to play an important role to increase the enantioselectivity. The
      methodology has successfully applied to the highly enantioselective hydroxylation
      of beta-keto esters using the DBFOX-Ni(II) complex.

PMID- 17177384
TI  - Hydrothermal synthesis of single-crystalline antimony telluride nanobelts.
AB  - The single-crystalline Sb2Te3 nanobelts were successfully synthesized by a novel
      and convenient surfactant-assisted hydrothermal approach. The ionic surfactant
      AOT acted as the shape controller in the synthetic process. We believe that this
      synthetic route could be applied to obtain other low-dimensional semiconducting
      telluride nanostructures.

PMID- 17177385
TI  - Denatured state effects and the origin of nonclassical phi values in protein
      folding.
AB  - Analysis of the phi value is one of the most powerful tools to understand the
      transition state for protein folding. In principle, phi values are expected to
      fall in the range of 0 to 1. However, a noticeable number of phi values have been
      observed which are either less than 0 or greater than 1. The origin of such phi
      values, sometimes referred to as noncanonical or nonclassical phi values, has
      been controversial. Here we show that mutational effects upon denatured state
      energetics can lead to nonclassical phi values.

PMID- 17177386
TI  - Highly oxidizing excited states of Re and Tc complexes.
AB  - Like the Re analogue, the ligand-to-metal charge transfer (LMCT) excited-state of
      [Tc(dmpe)3]2+ (dmpe is bis-1,2-(dimethylphosphino)ethane) is luminescent in
      solution at room temperature. Surprisingly, both [M(dmpe)3]2+* species have
      extremely large excited-state potentials (ESPs) as oxidants-the highest for any
      simple coordination complex of a transition metal. Furthermore, this potential is
      available using a photon of visible light (calculated for M = Re(Tc); E1/2* =
      +2.61(2.52) V versus SCE; lambdamax = 526(585) nm). Using a Rehm-Weller analysis
      with a series of aromatic hydrocarbons as electron-transfer quenchers,
      E1/2(Re2+*/Re+) has been determined to be 2.58 V, in good agreement with the
      calculated value. Both [M(dmpe)3]2+* species are quenched by chloride ion and
      both can function as excited-state oxidants in water solution.

PMID- 17177387
TI  - Palladium-catalyzed benzene arylation: incorporation of catalytic pivalic acid as
      a proton shuttle and a key element in catalyst design.
AB  - A palladium-pivalic acid cocatalyst system has been developed that exhibits
      unprecedented reactivity in direct arylation. This reactivity is illustrated with
      the first examples of high yielding direct metalation-arylation reactions of a
      completely unactivated arene, benzene. Experimental and computational evidence
      indicates that the pivalate anion is a key component in the palladation/C-H bond
      breaking event, that it lowers the energy of C-H bond cleavage and acts as a
      catalytic proton shuttle from benzene to the stoichiometric carbonate base. Eight
      examples of substituted aryl bromides are included which undergo direct arylation
      with benzene in 55-85% yield.

PMID- 17177388
TI  - Templated assembly of water-soluble nano-capsules: inter-phase sequestration,
      storage, and separation of hydrocarbon gases.
AB  - In aqueous solution, a deep-cavity cavitand was shown to self-assemble into
      dimeric nano-capsules via the sequestration of gaseous-phase hydrocarbons. The
      sequestration, assembly, and entrapment process was shown to be dependent on the
      hydrocarbon. Thus, by way of example, butane could be selectively sequestered
      from a propane-butane mixture.

PMID- 17177389
TI  - W(CO)5(L)-catalyzed tandem intramolecular cyclopropanation/cope rearrangement for
      the stereoselective construction of bicyclo[5.3.0]decane framework.
AB  - Utilizing the biscarbene character of electrophilically activated alkynes, a
      novel tandem intramolecular cyclopropanation/Cope rearrangement of 3-siloxy-1,3,9
      trien-7-ynes catalyzed by W(CO)5(L) for the stereoselective construction of
      bicyclo[5.3.0]decane framework is achieved. When 3-siloxy-1,3,9-trien-7-ynes were
      treated with a catalytic amount of W(CO)6 under photoirradiation,
      bicyclo[5.3.0]decanes were obtained in good yield stereoselectively. In this
      reaction, the Cope rearrangement of the divinylcyclopropane intermediates,
      generated by the intramolecular cyclopropanation of 3-siloxy-1,3,9-trien-7-ynes
      based on the W(CO)5(L)-catalyzed electrophilic activation of alkynes, occurs to
      give synthetically useful functionalized bicyclo[5.3.0]decane derivatives
      stereoselectively.

PMID- 17177390
TI  - Retinal counterion switch mechanism in vision evaluated by molecular simulations.
AB  - Photoisomerization of the retinylidene chromophore of rhodopsin is the starting
      point in the vision cascade. A counterion switch mechanism that stabilizes the
      retinal protonated Schiff base (PSB) has been proposed to be an essential step in
      rhodopsin activation. On the basis of vibrational and UV-visible spectroscopy,
      two counterion switch models have emerged. In the first model, the PSB is
      stabilized by Glu181 in the meta I state, while in the most recent proposal, it
      is stabilized by Glu113 as well as Glu181. We assess these models by conducting a
      pair of microsecond scale, all-atom molecular dynamics simulations of rhodopsin
      embedded in a 99-lipid bilayer of SDPC, SDPE, and cholesterol (2:2:1 ratio)
      varying the starting protonation state of Glu181. Theoretical simulations gave
      different orientations of retinal for the two counterion switch mechanisms, which
      were used to simulate experimental 2H NMR spectra for the C5, C9, and C13 methyl
      groups. Comparison of the simulated 2H NMR spectra with experimental data
      supports the complex-counterion mechanism. Hence, our results indicate that
      Glu113 and Glu181 stabilize the retinal PSB in the meta I state prior to
      activation of rhodopsin.

PMID- 17177391
TI  - Cationic palladium complex catalyzed highly enantioselective intramolecular
      addition of arylboronic acids to ketones. A convenient synthesis of optically
      active cycloalkanols.
AB  - An efficient and convenient synthesis of optically active cycloalkanols by
      utilizing the chiral cationic palladium complex as the catalyst was achieved in
      mild conditions with high yield and high enantioselectivity.

PMID- 17177392
TI  - Encodable activators of SRC family kinases.
AB  - There is considerable current interest in the design of encodable molecules that
      regulate intracellular protein circuitry and/or activity, ideally with a high
      level of specificity. Src homology 3 (SH3) domains are ubiquitous components of
      multidomain signaling proteins, including many kinases, and are attractive drug
      targets because of the important role their interactions play in diseases as
      diverse as cancer, osteoporosis, and inflammation. Here we describe a set of
      miniature proteins that recognize distinct SH3 domains from Src family kinases
      with high affinity. Three of these molecules discriminate effectively between the
      SH3 domains of Src and Fyn, which are expressed ubiquitously, and two of these
      three activate Hck kinase with potencies that rival HIV Nef, one of the most
      potent kinase activators known. These results suggest that miniature proteins
      represent a viable, encodable strategy for selective activation of Src family
      kinases in a variety of cell types.

PMID- 17177393
TI  - Photoreaction of a 2,11-diaza[3.3]paracyclophane derivative: formation of
      octahedrane by photochemical dimerization of benzene.
AB  - Upon photoirradiation at 300 nm, the title diazaparacyclophane (R = COCF3)
      provided an octahedrane by the photodimerization of its benzene chromophores.
      This is the first photochemical formation of octahedrane, namely, via the
      dimerization of benzene. No octahedrane formation was observed for the photolysis
      of corresponding carbon-bridged paracyclophane. Thus the nitrogen bridges play an
      important role in the excited state to afford the octahedrane.

PMID- 17177395
TI  - Isolation of a tetrameric cation-cation complex of pentavalent uranyl.
AB  - A polymetallic assembly containing mutually coordinated highly reactive UO2+
      groups was isolated in the presence of dibenzoylmethanate. NMR studies showed
      unambiguously the presence of the cation-cation complex in pyridine solution
      while more polar solvents lead to the disruption of the UO2+/UO2+ interaction and
      increased stability.

PMID- 17177394
TI  - Growth of ultrathin films of amorphous ruthenium-phosphorus alloys using a single
      source CVD precursor.
AB  - Thin films ( approximately 30 nm) of amorphous RuP alloys (P approximately 15
      20%) can be grown by CVD from the single source precursor cis-H2Ru(PMe3)4 at 250
      300 degrees C and 200 mTorr pressure on native SiO2.

PMID- 17177396
TI  - Quinone-annulated N-heterocyclic carbene-transition-metal complexes: observation
      of pi-backbonding using FT-IR spectroscopy and cyclic voltammetry.
AB  - A new N-heterocyclic carbene architecture comprising a 1,4-naphthoquinone
      annulated to 1,3-dimesitylimidazolylidene (NpQ-NHC) was synthesized in two high
      yielding steps from commercially available starting materials. The free NpQ-NHC
      was characterized (solution and solid-state) and was used to synthesize various
      Rh and Ag complexes that ranged in pi-electron density. Enabled by the quinone
      moiety, the pi-systems of these complexes were analyzed using infrared
      spectroscopy and cyclic voltammetry. In contrast to previous reports, pi
      backbonding was found to be non-negligible and was directly influenced by the
      metal's electronic character.

PMID- 17177397
TI  - Direct observation of the oxidative addition of the aryl carbon-oxygen bond to a
      ruthenium complex and consideration of the relative reactivity between aryl
      carbon-oxygen and aryl carbon-hydrogen bonds.
AB  - When RuH2(CO)(PPh3)3 was reacted with 2,2-dimethyl-1-(2-p-tolylphenyl)propan-1
      one (2), the ruthenium-aryloxy complex 3 was obtained in 76% yield. The structure
      of this complex was determined from 1H and 31P NMR and X-ray data. Complex 3
      showed the catalytic activity for the coupling of 2 with the phenylboronate 4.
      The 1H and 31P NMR studies of the reaction of Ru(CO)(PPh3)3 with o-aryloxy
      pivalophenone revealed that the C-H bond cleavage is a kinetically favorable
      process but the C-O bond cleavage is a thermodynamic one. The reaction of 2'
      methoxyacetophenone with vinylsilane and organoboronate resulted in
      chemoselective C-C bond formation.

PMID- 17177398
TI  - Diindolylquinoxalines: effective indole-based receptors for phosphate anion.
AB  - The synthesis of a new series of 2,3-diindol-3'yl quinoxalines (DIQ), as well as
      a comparison of their anion recognition properties to those of our previously
      reported pyrrole based sensors, 2,3-dipyrrol-2'yl quinoxalines, is reported. To
      the best of our knowledge, this new DIQ system represents the first example of a
      free-standing indole-based small molecule receptor for which evidence of anion
      binding is available both in solution and in the solid-state. It also provides
      one of the few structurally characterized neutral receptor-dihydrogen phosphate
      complexes. This work thus serves to demonstrate the utility of indoles as an
      anion recognition motif.

PMID- 17177399
TI  - Water penetration into protein secondary structure revealed by hydrogen-deuterium
      exchange two-dimensional infrared spectroscopy.
AB  - Two-dimensional infrared spectroscopy in conjunction with hydrogen-deuterium
      exchange experiments provides detailed information about solvent penetration into
      protein structure. Correlating the secondary-structure sensitivity of the amide I
      vibration and the solvent-exposure sensitivity of amide II provides a direct
      probe of solvent-inaccessible residues of proteins embedded in the hydrophobic
      core or those involved in strong hydrogen bonds in secondary structures. Distinct
      spectral signatures of the cross-peak region arising from the coupling of the
      amide I and II modes imply a significant degree of structural stability of
      hydrogen-bonded contacts in alpha-helices and beta-sheets in a series of
      proteins. Ubiquitin, an alpha/beta-protein, exhibits strong alpha-helical
      signatures and lacks those of the beta-sheet in the cross-peak region,
      demonstrating that ubiquitin's beta-sheet exchanges protons with the surrounding
      solvent and is conformationally unstable.

PMID- 17177400
TI  - Synthesis of colloidal uranium-dioxide nanocrystals.
AB  - In this paper, we have developed an organic-phase synthesis method for producing
      size-controlled, nearly monodispersed, colloidal uranium-dioxide nanocrystals.
      These UO2 nanocrystals are potentially important to applications such as nuclear
      fuel materials, catalysts, and thermopower materials. In addition, we have
      systematically mapped out the functions of the solvents (oleic acid, oleylamine,
      and 1-octadecene) in the synthesis, and we found that N-(cis-9
      octadecenyl)oleamide-a product of the condensation of oleic acid and oleylamine
      can substantially affect the formation of UO2 nanocrystals. Importantly, these
      results provide fundamental insight into the mechanisms of UO2 nanocrystal
      synthesis. Moreover, because a mixture of oleic acid and oleylamine has been
      widely used in synthesizing a variety of high-quality metal or metal-oxide
      nanocrystals, the results herein should also be important for understanding the
      detailed mechanisms of these syntheses.

PMID- 17177401
TI  - Excited-state mixed-valence distortions in a diisopropyl diphenyl hydrazine
      cation.
AB  - Excited-state mixed valence (ESMV) occurs in the 1,2-diphenyl-1,2-diisopropyl
      hydrazine radical cation, a molecule in which the ground state has a symmetrical
      charge distribution localized primarily on the hydrazine, but the phenyl to
      hydrazine charge-transfer excited state has two interchangeably equivalent phenyl
      groups that have different formal oxidation states. Electronic absorption and
      resonance Raman spectra are presented. The neighboring orbital model is employed
      to interpret the absorption spectrum and coupling. Resonance Raman spectroscopy
      is used to determine the excited-state distortions. The frequencies of the
      enhanced modes from the resonance Raman spectra are used together with the time
      dependent theory of spectroscopy to fit the two observed absorption bands that
      have resolved vibronic structure. The origins of the vibronic structure and
      relationships with the neighboring orbital model are discussed.

PMID- 17177402
TI  - Control of interchain contacts, solid-state fluorescence quantum yield, and
      charge transport of cationic conjugated polyelectrolytes by choice of anion.
AB  - Simple procedures are provided for exchanging charge-compensating ions in
      conjugated polyelectrolytes by progressive dilution of the original species and
      for determining the degree of ion exchange by using X-ray photoelectron
      spectroscopy. By using these methods, the bromide ions in poly[(9,9-bis(6'-N,N,N
      trimethylammoniumbromide)hexyl)fluorene-co-alt-4,7-(2,1,3-benzothiadiazole)]were
      exchanged with BF4-, CF3SO3-, PF6-, BPh4-, and B(3,5-(CF3)2C6H3)4- (BArF4-).
      Absorption, photoluminescence (PL), and PL quantum yields (Phi) were measured in
      different solvents and in solid films cast from methanol. Examination of the
      resulting trends, together with the spectral bandshapes in different solvents,
      suggests that increasing the counteranion (CA) size decreases interchain contacts
      and aggregation and leads to a substantial increase of Phi in the bulk. Size
      analysis of polymers containing Br- and BArF4- in water by dynamic light
      scattering techniques indicates suppression of aggregation by BArF4-. Nanoscale
      current-voltage measurements of films using conducting atomic force microscopy
      show that hole mobilities and, more significantly, charge injection barriers are
      CA dependent. These results show that it is possible to significantly modify the
      optoelectronic properties of conjugated polyelectrolytes by choosing different
      counterions. A parent conjugated backbone can thus be fine-tuned for specific
      applications.

PMID- 17177404
TI  - Singlet fission for dye-sensitized solar cells: can a suitable sensitizer be
      found?
AB  - We discuss possible improvements in the efficiency of dye-sensitized photovoltaic
      cells using dyes capable of singlet fission into two triplets, thus producing two
      electron-hole pairs from a single photon. It is pointed out that, in addition to
      derivatives of large alternant hydrocarbons, those of biradicals are also likely
      candidates for a favorable ordering of excited-state energy levels, E(T2), E(S1)
      > 2E(T1). A large number of potentially favorable structures has been examined by
      the semiempirical Pariser-Parr-Pople method and some also by the time-dependent
      density functional theory method. Several likely candidates have been identified
      for experimental examination.

PMID- 17177403
TI  - Active site labeling of G8 in the hairpin ribozyme: implications for structure
      and mechanism.
AB  - There is mounting evidence that suggests that general acid/base catalysis is
      operative in the hairpin ribozyme, with analogy to the protein enzyme RNaseA.
      Nevertheless, the extent of general base catalysis as well as the identity of the
      specific chemical groups responsible remains the subject of some controversy. An
      affinity label has previously been used to alkylate histidine 12 (His12), the
      active general base in RNaseA. To date, no such experiment has been applied to a
      ribozyme. We have synthesized the analogous affinity label for the hairpin
      ribozyme with an electrophilic 2'-bromoacetamide group in lieu of the 2'-hydroxyl
      (2'OH) at the substrate cleavage site and show that guanosine 8 (G8) of the
      hairpin ribozyme is specifically alkylated, most likely at the N1 position. This
      evidence strongly implicates N1 of G8 in active site chemistry. By direct analogy
      to RNase A, these findings could be consistent with the hypothesis that
      deprotonated G8 residue functions as a general base in the hairpin ribozyme.
      Other mechanistic possibilities for N1 of G8 such as indirect general base
      catalysis mediated by a water molecule or transition state stabilization could
      also be consistent with our findings.

PMID- 17177405
TI  - Electronic communication and negative binding cooperativity in diborylated
      bithiophenes.
AB  - The bifunctional conjugated organoboranes Ar2B-bt-BAr2, which contain 2,2'
      bithiophene (bt) linkers and different aryl substituents on boron (3: Ar = p
      tBuC6H4; 4: Ar = C6F5; 5: Ar = C6F5, Fc; Fc = ferrocenyl), have been synthesized.
      The electronic communication between the boron centers and cooperativity effects
      in the binding of pyridine have been investigated by a comprehensive study using
      X-ray crystallography, DFT calculations, cyclic voltammetry, 1H and 19F NMR, and
      UV visible absorption and emission spectroscopy. A comparison of the single
      crystal X-ray structures of 4 and 4Py2 revealed a strongly diminished bond
      alternation in the thiophene rings for 4, indicative of a high degree of
      electronic delocalization. DFT calculations are in good agreement with the
      structural features determined from the X-ray analysis and, consistent with the
      experimental absorption and emission data, predict a smaller HOMO-LUMO gap for
      green luminescent 4 in comparison to blue luminescent 3. The complexation of
      pyridine to the two boron centers was further investigated by 1H and 19F NMR for
      4 and by 1H NMR and UV-visible absorption spectroscopy for 3. We found that
      binding of the first pyridine molecule to one of the boryl groups significantly
      lowers the Lewis acidity of the other boryl group. For 3, the interaction
      parameter a, which provides a measure of communication between the boron sites,
      was determined to be a = 0.23 by UV-visible titration and 0.21 by 1H NMR
      spectroscopy. Further enhanced electronic communication was observed for the more
      highly Lewis acidic fluorinated derivative 4, for which a = 0.025 according to
      19F and 1H NMR spectroscopy.

PMID- 17177406
TI  - Comparing the electronic properties of the low-spin cyano-ferric [Fe(N4)(Cys)]
      active sites of superoxide reductase and p450cam using ENDOR spectroscopy and DFT
      calculations.
AB  - Superoxide reductase (SOR) and P450 enzymes contain similar [Fe(N)4(SCys)] active
      sites and, although they catalyze very different reactions, are proposed to
      involve analogous low-spin (hydro)peroxo-Fe(III) intermediates in their
      respective mechanisms that can be modeled by cyanide binding. The equatorial FeN4
      ligation by four histidine ligands in CN-SOR and the heme in CN-P450cam is
      directly compared by 14N ENDOR, while the axial Fe-CN and Fe-S bonding is probed
      by 13C ENDOR of the cyanide ligand and 1Hbeta ENDOR measurements to determine the
      spin density delocalization onto the cysteine sulfur. There are small, but
      notable, differences in the bonding between Fe(III) and its ligands in the two
      enzymes. The ENDOR measurements are complemented by DFT computations that support
      the semiempirical equation used to compute spin densities on metal-coordinated
      cysteinyl and shed light on bonding changes as the Fe-C-N linkage bends. They
      further indicate that H bonds to the cysteinyl thiolate sulfur ligand reduce the
      spin density on the sulfur in both active sites to a degree that exceeds the
      difference induced by the alternative sets of "in-plane" nitrogen ligands.

PMID- 17177407
TI  - Thickness dependence of microstructure in semiconducting films of an
      oligofluorene derivative.
AB  - The measurement and optimization of microstructure development in organic
      semiconductor films is valuable because microstructure in many cases critically
      impacts electronic performance. We demonstrate a general method to measure
      microstructure thickness dependence in thin films using surface-sensitive near
      edge X-ray absorbance fine structure (NEXAFS) spectroscopy. The method is applied
      to an oligofluorene derivative DDFTTF, which consists of a fluorene-bithiophene
      fluorene core that is end-substituted with linear dodecyl groups. The substrate
      relative orientations of the aromatic core and the aliphatic end chains are
      independently determined, and comparing these orientations to terrace heights
      from atomic force micrographs proves that the end chains are interdigitated or
      folded. By measuring microstructure development from 6 to 150 nm, we find that
      DDFTTF exhibits two different preferential microstructures: one with large
      terraces within which molecules exhibit a strongly vertical orientation, and one
      with much smaller domains within which molecules exhibit a mildly horizontal
      orientation. The relative distribution of these two preferential microstructures
      depends on the distance of the domains from the substrate and the substrate
      temperature during deposition. The utility of this method is tested using a
      lamination technique to measure the saturation hole mobility at the top and
      bottom interface of DDFTTF films. We find that local microstructures with greater
      pi orbital alignment in the source-drain plane correlate directly to better local
      saturation hole mobilities.

PMID- 17177408
TI  - Electrochemical oxidation of CoCp(CO)2: radical-substrate reaction of a 17 e-/18
      e- pair and production of a unique dimer radical.
AB  - Anodic oxidation of the important half-sandwich compound CoCp(CO)2, 1, has been
      studied under gentle electrolyte conditions, e.g., chlorinated hydrocarbons with
      weakly coordinating anion (WCA) supporting electrolyte anions. The 17-electron
      cation 1+ produced at E(1/2)(1) = 0.37 V vs FeCp2(0/+) undergoes a surprising
      reaction with neutral 1 to form the dimer radical cation [Co2Cp2(CO)4] +, 2+,
      which has a metal-metal bond unsupported by bridging ligands. The dimer radical
      is oxidized at a slightly more positive potential (E(1/2) = 0.47 V) to the
      corresponding dication 2(2+). Observation of the oxidation of 2+ is without
      precedent in confirming a radical-substrate (R-S) dimerization process by direct
      voltammetric detection of the R-S intermediate, K(eq) = 3 x 10(4) M(-1) for
      [2+]/[1][1+]. The R-S mechanism and the reaction products have been characterized
      by voltammetry, electrolysis, fiber-optic IR spectroscopy, and ESR measurements.
      DFT calculations indicate that removal of an electron from 1 results in
      rehybridization in 1+, thereby opening the metal center for interaction with the
      neutral compound 1, which has a relatively basic metal center. The LUMO of the
      dimer dication 2(2+) is metal-metal antibonding, and its half-occupancy in 2+
      results in lengthening of the Co-Co bond from 2.64 A to 3.14 A. Inclusion of
      solvent in the (COSMO) calculations shows that solvation effects are necessary to
      account for the fact that E(1/2)(2) > E(1/2)(1). These results show the
      importance of medium effects in probing the fundamental redox chemistry of half
      sandwich metal complexes.

PMID- 17177409
TI  - Carbon-oxygen bond cleavage with eta9,eta5-bis(indenyl)zirconium sandwich
      complexes.
AB  - Treatment of the eta9,eta5-bis(indenyl)zirconium sandwich complex, (eta9-C9H5-1,3
      (SiMe3)2)(eta5-C9H5-1,3-(SiMe3)2)Zr, with dialkyl ethers such as diethyl ether,
      CH3OR (R=Et, nBu, tBu), nBu2O, or iPr2O resulted in facile C-O bond scission
      furnishing an eta5,eta5-bis(indenyl)zirconium alkoxy hydride complex and free
      olefin. In cases where ethylene is formed, trapping by the zirconocene sandwich
      yields a rare example of a crystallographically characterized, base-free
      eta5,eta5-bis(indenyl)zirconium ethylene complex. Observation of normal, primary
      kinetic isotope effects in combination with rate studies and the stability of
      various model compounds support a mechanism involving rate-determining C-H
      activation to yield an eta5,eta5-bis(indenyl)zirconium alkyl hydride intermediate
      followed by rapid beta-alkoxide elimination. For isolable eta6,eta5
      bis(indenyl)zirconium THF compounds, thermolysis at 85 degrees C also resulted in
      C-O bond cleavage to yield the corresponding zirconacycle. Both mechanistic and
      computational studies again support a pathway involving haptotropic rearrangement
      to eta5,eta5-bis(indenyl)zirconium intermediates that promote rate-determining C
      H activation and ultimately C-O bond scission.

PMID- 17177410
TI  - Two-dimensional porous molecular networks of dehydrobenzo[12]annulene derivatives
      via alkyl chain interdigitation.
AB  - The self-assembly of a series of hexadehydrotribenzo[12]annulene (DBA)
      derivatives has been scrutinized by scanning tunneling microscopy (STM) at the
      liquid-solid interface. First, the influence of core symmetry on the network
      structure was investigated by comparing the two-dimensional (2D) ordering of
      rhombic bisDBA 1a and triangular DBA 2a (Figure 1). BisDBA 1a forms a Kagome
      network upon physisorption from 1,2,4-trichlorobenzene (TCB) onto highly oriented
      pyrolytic graphite (HOPG). Under similar experimental conditions, DBA 2a shows
      the formation of a honeycomb network. The core symmetry and location of alkyl
      substituents determine the network structure. The most remarkable feature of the
      DBA networks is the interdigitation of the nonpolar alkyl chains: they connect
      the pi-conjugated cores and direct their orientation. As a result, 2D open
      networks with voids are formed. Second, the effect of alkyl chain length on the
      structure of DBA patterns was investigated. Upon increasing the length of the
      alkyl chains (DBAs 3c-e) a transition from honeycomb networks to linear networks
      was observed in TCB, an observation attributed to stronger molecule-substrate
      interactions. Third, the effect of solvent on the structure of the nonpolar DBA
      networks was investigated in four different solvents: TCB as a polar aromatic
      solvent, 1-phenyloctane as a solvent having both aromatic and aliphatic moieties,
      n-tetradecane as an aliphatic solvent, and octanoic acid as a polar alkylated
      solvent. The solvent dramatically changes the structure of the DBA networks. The
      solvent effects are discussed in terms of factors that influence the mobility of
      molecules at the liquid-solid interface such as solvation.

PMID- 17177412
TI  - Anodic electrodeposition of highly oriented zirconium phosphate and polyaniline
      intercalated zirconium phosphate films.
AB  - Films of highly oriented alpha-zirconium phosphate and polyaniline-intercalated
      zirconium phosphate with controllable thickness in the micrometer range were
      grown anodically on Pt electrodes. To optimize the electrodeposition conditions,
      the exfoliation of alpha-zirconium phosphate by tetrabutylammonium (TBA) salts
      was investigated in several nonaqueous solvents. Acetonitrile was found to be the
      best solvent for making crack-free, oriented films because of its high vapor
      pressure, low viscosity, and relatively high permittivity. With TBA salts of
      neutral or weakly acidic anions (TBACl, TBABr, TBAI, TBA(HSO4), or TBA(H2PO4)),
      full exfoliation did not occur and alpha-zirconium phosphate and/or polyaniline
      were deposited as rough films. With basic anions (TBAF or TBAOH), dense, adherent
      films were obtained. X-ray diffraction patterns of the films showed that they
      were highly oriented along the stacking axis. The thickness could be controlled,
      up to about 40 microm, by limiting the time of the electrodeposition reaction. At
      monomer concentrations below 1.0 x 10(-2) mol/dm3, the emeraldine form of the
      intercalated polymer was obtained. Electrodeposition thus provides a thick film
      alternative to layer-by-layer assembly for intercalation compounds of alpha
      zirconium phosphate with a conducting polymer.

PMID- 17177411
TI  - Targeting of cancer cells with ferrimagnetic ferritin cage nanoparticles.
AB  - Protein cage architectures such as virus capsids and ferritins are versatile
      nanoscale platforms amenable to both genetic and chemical modification.
      Incorporation of multiple functionalities within these nanometer-sized protein
      architectures demonstrate their potential to serve as functional nanomaterials
      with applications in medical imaging and therapy. In the present study, we
      synthesized an iron oxide (magnetite) nanoparticle within the interior cavity of
      a genetically engineered human H-chain ferritin (HFn). A cell-specific targeting
      peptide, RGD-4C which binds alphavbeta3 integrins upregulated on tumor
      vasculature, was genetically incorporated on the exterior surface of HFn. Both
      magnetite-containing and fluorescently labeled RGD4C-Fn cages bound C32 melanoma
      cells in vitro. Together these results demonstrate the capability of a
      genetically modified protein cage architecture to serve as a multifunctional
      nanoscale container for simultaneous iron oxide loading and cell-specific
      targeting.

PMID- 17177413
TI  - Dark-field oxidative addition-based chemosensing: new bis-cyclometalated PtII
      complexes and phosphorescent detection of cyanogen halides.
AB  - Heavy metal complexes that are phosphorescent at room temperature are becoming
      increasingly important in materials chemistry, principally due to their use in
      phosphorescent organic light-emitting devices (OLEDs). Their use in optical
      sensory schemes, however, has not been heavily explored. Homoleptic bis
      cyclometalated Pt(II) complexes are known to undergo oxidative addition with
      appropriate electrophiles (principally alkyl halides) by either thermal or
      photochemical activation. We have applied this general reaction scheme to the
      development of a phosphorescence-based sensing system for cyanogen halides. To
      carry out structure-property relationship studies, a series of previously
      unreported Pt(II) complexes was prepared. Most of the complexes (excluding those
      that incorporated substituents on the ligands that forced steric crowding in the
      square plane) were strongly orange-red phosphorescent (Phi = 0.2-0.3) in a room
      temperature oxygen-free solution. These sterically demanding ligands also
      accelerated the addition of cyanogen bromide to these complexes but slowed the
      addition of methyl iodide, indicating that the oxidative addition mechanisms for
      these two electrophiles is different. The lack of solvent-polarity effect on the
      addition of BrCN suggests a radical mechanism. Oxidative addition of BrCN to the
      metal complexes in solution or dispersed in poly(methyl methacrylate) gave blue
      shifted emissive Pt(IV) complexes. The blue-shifted products give a dark-field
      sensing scheme that is in sharp contrast to energy transfer-based sensing
      schemes, which have limited signal-to-noise because of the presence of lower
      energy vibronic bands of the energy donor that can overlap with the emission of
      the acceptor.

PMID- 17177414
TI  - Stereospecificity in metallocene catalyzed acrylate polymerizations: the chiral
      orientation of the growing chain selects its own chain end enantioface.
AB  - The mechanism of stereocontrol in the site-controlled stereospecific
      polymerization of methyl methacrylate (MMA) with C2- and CS-symmetric
      zirconocenes is investigated with a DFT based approach. Our model explains the
      experimentally observed isospecificity in MMA polymerization with the C2
      symmetric rac-C2H4(Ind)2Zr-based system as well as the experimentally observed
      syndiospecificity in MMA polymerization with the CS-symmetric Me2C(Cp)(Flu)Zr
      based system. In both cases, the chiral metallocene induces a chiral orientation
      of the ester enolate growing chain. In turn, the chirally oriented growing chain
      selects its own enantioface. Comparison with the mechanism of stereocontrol
      operative in the case of propene polymerization by the same zirconocenes is
      performed to stress similarities and differences. Although analogies are
      expected, surprising differences also exist. The most peculiar is that the in the
      case of 1-olefins, the enantioselective event is selection between the
      enantiofaces of the prochiral monomer. Instead, in the case of acrylates, the
      enantioselective event is selection between the enantiofaces of the prochiral
      growing chain.

PMID- 17177416
TI  - Synthesis of oligoenes that contain up to 15 double bonds from 1,6-heptadiynes.
AB  - This paper reports the synthesis of polyene oligomers ("oligoenes") that contain
      up to 15 double bonds that are identical to the "all five-membered ring" species
      formed through cyclopolymerization of diisopropyldipropargylmalonate. The
      oligoenes contain an isopropylidene unit at each end. The isolated oligoenes
      range from the "dimer" (a pentaene, (E)-di-1,2-[1-(2-methyl-propenyl)-4,4-di-iso
      propyl-carboxy-cyclopent-1-enyl]-ethene (3b2)) to the "heptamer" (3b7, a
      pentadecaene). Oligoenes 3b2, 3b3, 3b4, 3b5, and 3b7 were prepared through Wittig
      like reactions between aldehydes and the appropriate monometallic Mo alkylidene
      or bimetallic Mo bisalkylidene species whose alkylidene is derived from an
      identical five-membered ring monomeric unit. Compounds 3b2, 3b4, and 3b6 were
      prepared through McMurry coupling reactions of aldehydes. A representative
      aldehyde (the "monomeric" aldehyde) is diisopropyl-3-formyl-4-(2-methylprop-1
      enyl)cyclopent-3-ene-1,1-dicarboxylate (2b), McMurry coupling of which yields
      3b2. A heptaene that contains a six-membered ring in the central unit also was
      prepared in a Wittig-like reaction involving a bimetallic Mo alkylidene; this
      species is a model for oligoenes that contain both six-membered and five-membered
      rings. X-ray structures of two bimetallic species that are employed in the
      synthesis of the oligoenes are reported.

PMID- 17177415
TI  - Calculation of vibronic couplings for phenoxyl/phenol and benzyl/toluene self
      exchange reactions: implications for proton-coupled electron transfer mechanisms.
AB  - The vibronic couplings for the phenoxyl/phenol and the benzyl/toluene self
      exchange reactions are calculated with a semiclassical approach, in which all
      electrons and the transferring hydrogen nucleus are treated quantum mechanically.
      In this formulation, the vibronic coupling is the Hamiltonian matrix element
      between the reactant and product mixed electronic-proton vibrational
      wavefunctions. The magnitude of the vibronic coupling and its dependence on the
      proton donor-acceptor distance can significantly impact the rates and kinetic
      isotope effects, as well as the temperature dependences, of proton-coupled
      electron transfer reactions. Both of these self-exchange reactions are
      vibronically nonadiabatic with respect to a solvent environment at room
      temperature, but the proton tunneling is electronically nonadiabatic for the
      phenoxyl/phenol reaction and electronically adiabatic for the benzyl/toluene
      reaction. For the phenoxyl/phenol system, the electrons are unable to rearrange
      fast enough to follow the proton motion on the electronically adiabatic ground
      state, and the excited electronic state is involved in the reaction. For the
      benzyl/toluene system, the electrons can respond virtually instantaneously to the
      proton motion, and the proton moves on the electronically adiabatic ground state.
      For both systems, the vibronic coupling decreases exponentially with the proton
      donor-acceptor distance for the range of distances studied. When the transferring
      hydrogen is replaced with deuterium, the magnitude of the vibronic coupling
      decreases and the exponential decay with distance becomes faster. Previous
      studies designated the phenoxyl/phenol reaction as proton-coupled electron
      transfer and the benzyl/toluene reaction as hydrogen atom transfer. In addition
      to providing insights into the fundamental physical differences between these two
      types of reactions, the present analysis provides a new diagnostic for
      differentiating between the conventionally defined hydrogen atom transfer and
      proton-coupled electron transfer reactions.

PMID- 17177417
TI  - Ab initio calculations of the potential surface for rearrangement of 2,2,3,3
      tetrafluoromethylenecyclopropane to 1-(difluoromethylene)-2,2
      difluorocyclopropane.
AB  - (4/4)CASSCF and CASPT2 calculations have been performed to understand the reason
      that addition of a second pair of geminal fluorines to methylenecyclopropane
      lowers the barrier to rearrangement by 6.7 kcal/mol more than addition of the
      first pair. Our calculations duplicate this experimental finding by Dolbier and
      co-workers. Our computational results confirm Dolbier's conjecture, that the non
      additive lowering of Ea for the rearrangement of 2,2,3,3
      tetrafluoromethylenecyclopropane (9) to 1-(difluoromethylene)-2,2
      difluorocyclopropane (11) is due to destabilization of 9 by the presence of the
      vicinal CF2 groups in this fluorocarbon. In the course of exploring the potential
      energy surface for the rearrangement of 9, we have located a bond-stretch isomer
      (20) that differs from 9 by inversion of both CF2 groups. The enthalpy of 20 is
      computed to be 21.9 kcal/mol higher than that of 9, but direct interconversion of
      these two "bond-stretch invertomers" requires passage over a TS whose enthalpy is
      calculated to be 11.7 kcal/mol higher than that of 20.

PMID- 17177419
TI  - Dynamic processes in [16]annulene: Mobius bond-shifting routes to configuration
      change.
AB  - Density functional and ab initio methods have been used to study the mechanisms
      for key dynamic processes of the experimentally known S4-symmetric [16]annulene
      (1a). Using BH&HLYP/6-311+G** and B3LYP/6-311+G**, we located two viable stepwise
      pathways with computed energy barriers (Ea = 8-10 kcal/mol) for conformational
      automerization of 1a, in agreement with experimental data. The transition states
      connecting these conformational minima have Mobius topology and serve as starting
      points for non-degenerate pi-bond shifting (configuration change) via Mobius
      aromatic transition states. The key transition state, TS1-2, that connects the
      two isomers of [16]annulene (CTCTCTCT, 1 --> CTCTTCTT, 2) has an energy, relative
      to the S4 isomer, that ranged from 6.9 kcal/mol (B3LYP/6-311+G**) to 16.7
      kcal/mol (BH&HLYP/6-311+G**), bracketing the experimental barrier. At our best
      level of theory, CCSD(T)/cc-pVDZ(est), this barrier is 13.7 kcal/mol. Several
      other Mobius bond-shifting transition states, as well as Mobius topology
      conformational minima, were found with BH&HLYP energies within 22 kcal/mol of 1a,
      indicating that many possibilities exist for facile thermal configuration change
      in [16]annulene. This bond-shifting mechanism and the corresponding low barriers
      contrast sharply with those observed for cis/trans isomerization in acyclic
      polyenes, which occurs via singlet diradical transition states. All Mobius bond
      shifting transition states located in [16]- and [12]annulene were found to have
      RHF --> UHF instabilities with the BH&HLYP method but not with B3LYP. This result
      appears to be an artifact of the BH&HLYP method. These findings support the idea
      that facile thermal configuration change in [4n]annulenes can be accounted for by
      mechanisms involving twist-coupled bond shifting.

PMID- 17177418
TI  - Synthetic seleno-glutaredoxin 3 analogues are highly reducing oxidoreductases
      with enhanced catalytic efficiency.
AB  - Selenoenzymes have a central role in maintaining cellular redox potential. These
      enzymes have selenenylsulfide bonds in their active sites that catalyze the
      reduction of peroxides, sulfoxides, and disulfides. The selenol/disufide exchange
      reaction is common to all of these enzymes, and the active site redox potential
      reflects the ratio between the forward and reverse rates of this reaction. The
      preparation of enzymes containing selenocysteine (Sec) is experimentally
      challenging. As a result, little is known about the kinetic role of selenols in
      enzyme active sites, and the redox potential of a selenenylsulfide or diselenide
      bond in a protein has not been experimentally determined. To fully evaluate the
      effects of Sec on oxidoreductase redox potential and kinetics, glutaredoxin 3
      (Grx3) and all three Sec variants of its conserved (11)CXX(14)C active site were
      chemically synthesized. Grx3, Grx3(C11U), and Grx3(C14U) exhibited redox
      potentials of -194, -260, and -275 mV, respectively. The position of redox
      equilibrium between Grx3(C11U-C14U) (-309 mV) and thioredoxin (Trx) (-270 mV)
      suggests a possible role for diselenide bonds in biological systems. Kinetic
      analysis is consistent with the hypothesis that the lower redox potentials of the
      Sec variants result primarily from the greater nucleophilicity of the active site
      selenium rather than its role as either a leaving group or a "central atom" in
      the exchange reaction. The 10(2)-10(4)-fold increase in the rate of Trx reduction
      by the seleno-Grx3 analogues demonstrates that oxidoreductases containing either
      selenenyl-sulfide or diselenide bonds can have physiologically compatible redox
      potentials and enhanced reduction kinetics in comparison with their sulfide
      counterparts.

PMID- 17177420
TI  - Molecular engineering of organic sensitizers for solar cell applications.
AB  - Novel organic sensitizers comprising donor, electron-conducting, and anchoring
      groups were engineered at molecular level and synthesized. The functionalized
      unsymmetrical organic sensitizers 3-{5-[N,N-bis(9,9-dimethylfluorene-2-yl)phenyl]
      thiophene-2-yl}-2-cyano-acrylic acid (JK-1) and 3-{5'-[N,N-bis(9,9
      dimethylfluorene-2-yl)phenyl]-2,2'-bisthiophene-5-yl}-2-cyano-acrylic acid (JK
      2), upon anchoring onto TiO2 film, exhibit unprecedented incident photon to
      current conversion efficiency of 91%. The photovoltaic data using an electrolyte
      having composition of 0.6 M M-methyl-N-butyl imidiazolium iodide, 0.04 M iodine,
      0.025 M LiI, 0.05 M guanidinium thiocyanate, and 0.28 M tert-butylpyridine in a
      15/85 (v/v) mixture of valeronitrile and acetonitrile revealed a short circuit
      photocurrent density of 14.0 +/- 0.2 mA/cm2, an open circuit voltage of 753 +/-
      10 mV, and a fill factor of 0.76 +/- 0.02, corresponding to an overall conversion
      efficiency of 8.01% under standard AM 1.5 sunlight. DFT/TDDFT calculations have
      been performed on the two organic sensitizers to gain insight into their
      structural, electronic, and optical properties. Our results show that the
      cyanoacrylic acid groups are essentially coplanar with respect to the thiophene
      units, reflecting the strong conjugation across the thiophene-cyanoacrylic
      groups. Molecular orbitals analysis confirmed the experimental assignment of
      redox potentials, while TDDFT calculations allowed assignment of the visible
      absorption bands.

PMID- 17177421
TI  - Quinones as electron acceptors. X-ray structures, spectral (EPR, UV-vis)
      characteristics and electron-transfer reactivities of their reduced anion
      radicals as separated vs contact ion pairs.
AB  - Successful isolation of a series of pure (crystalline) salts of labile quinone
      anion radicals suitable for X-ray crystallographic analysis allows for the first
      time their rigorous structural distinction as "separated" ion pairs (SIPs) vs
      "contact" ion pairs (CIPs). The quantitative evaluation of the precise changes in
      the geometries of these quinones (Q) upon one-electron reduction to afford the
      anion radical (Q-*) is viewed relative to the corresponding (two-electron)
      reduction to the hydroquinone (H2Q) via the Pauling bond-length/bond-order
      paradigm. Structural consequences between such separated and contact ion pairs as
      defined in the solid state with those extant in solution are explored in the
      context of their spectral (EPR, UV-vis) properties and isomerization of tightly
      bound CIPs. Moreover, the SIP/CIP dichotomy is also examined in intermolecular
      interactions for rapid (self-exchange) electron transfer between Q-* and Q with
      second-order rate constants of kET approximately equal to 10(8) M-1 s-1, together
      with the spectral observation of the paramagnetic intermediates [Q,Q-*]leading to
      1:1 adducts, as established by X-ray crystallography.

PMID- 17177423
TI  - Deviation from the planarity--a large Dy3N cluster encapsulated in an Ih-C80
      cage: an X-ray crystallographic and vibrational spectroscopic study.
AB  - The high-yield synthesis of Dy3N@C80 (I) opens the possibility of characterizing
      its molecular and vibrational structures. We report on the structure
      determination of Dy3N@C80 (I) by X-ray crystallographic study of single crystal
      of Dy3N@C80.Ni(OEP).2C6H6, revealing a nearly planar Dy3N cluster encapsulated in
      an Ih-C80 cage. The vibrational structure of Dy3N@C80 (I) is studied by Fourier
      transform infrared (FTIR) and Raman spectroscopy in combination with force-field
      calculations. A correlation was found between the antisymmetric metal-nitrogen
      stretching vibration and the structure of the M3N cluster of M3N@C80 (I) (M = Y,
      Gd, Tb, Dy, Ho, Er, Tm). Moreover, a stronger interaction between the encaged
      nitride cluster and the C80 carbon cage was found in the class II M3N@C80 (I) (M
      = Y, Gd, Tb, Dy, Ho, Er, Tm) than in Sc3N@C80 (I). This study demonstrates that
      the cluster size plays the dominating role in the structure of the M3N cluster in
      M3N@C80 (I).

PMID- 17177422
TI  - Total synthesis and evaluation of cytostatin, its C10-C11 diastereomers, and
      additional key analogues: impact on PP2A inhibition.
AB  - The total synthesis of cytostatin, an antitumor agent belonging to the fostriecin
      family of natural products, is described in full detail. The convergent approach
      relied on a key epoxide-opening reaction to join the two stereotriad units and a
      single-step late-stage stereoselective installation of the sensitive (Z,Z,E)
      triene through a beta-chelation-controlled nucleophilic addition. The synthetic
      route provided rapid access to the C4-C6 stereoisomers of the cytostatin lactone,
      which were prepared and used to define the C4-C6 relative stereochemistry of the
      natural product. In addition to the natural product, each of the C10-C11
      diastereomers of cytostatin was divergently prepared (11 steps from key
      convergence step) by this route and used to unequivocally confirm the relative
      and absolute stereochemistry of cytostatin. Each of the cytostatin diastereomers
      exhibited a reduced activity toward inhibition of PP2A (>100-fold), demonstrating
      the importance of the presence and stereochemistry of the C10-methyl and C11
      hydroxy groups for potent PP2A inhibition. Extensions of the studies provided
      dephosphocytostatin, sulfocytostatin (a key analogue related to the natural
      product sultriecin), 11-deshydroxycytostatin, and an analogue lacking the entire
      C12-C18 (Z,Z,E)-triene segment, which were used to define the magnitude of the C9
      phosphate (>4000-fold), C11-alcohol (250-fold), and triene (220-fold)
      contribution to PP2A inhibition. A model of cytostatin bound to the active site
      of PP2A is presented, compared to that of fostriecin, which is also presented in
      detail for the first time, and used to provide insights into the role of the key
      substituents. Notably, the alpha,beta unsaturated lactone of cytostatin, like
      that of fostriecin, is projected to serve as a key electrophile, providing a
      covalent adduct with Cys269 unique to PP2A, contributing to its potency (> or
      =200-fold for fostriecin) and accounting for its selectivity.

PMID- 17177424
TI  - Giant macrocycles composed of thiophene, acetylene, and ethylene building blocks.
AB  - Fully conjugated giant macrocyclic oligothiophenes with 60pi, 90pi,120pi, 150pi,
      and 180pi frames (1, 2, 3, 4 and 5) have been designed, and their butyl
      substituted derivatives (1a, 2a, 3a, 4a, and 5a) have been synthesized using
      modified Sonogashira and McMurry coupling reactions as key steps. The 60-180pi
      systems 1-5 are circular with 1.8-6 nm inner cavities and 3.3-7.5 nm outside
      molecular diameters. Compound 1a containing ten 3,4-dibutyl-2,5-thienylene, eight
      ethynylene, and two vinylene units has been converted into macrocyclic oligo(3,4
      dibutyl-2,5-thienylene-ethynylene) 6a using bromination/dehydrobromination
      procedure. Giant macrocycles 1a-6a exhibit a red shift of their absorption
      spectra and a fairly strong fluorescence with a large Stokes shift as compared to
      a linear conjugated counterpart having five thiophene rings. Compounds 1a-6a
      exhibit multistep reversible redox behaviors with fairly low first oxidation
      potentials, reflecting their cyclic conjugation. Furthermore, chemical oxidation
      of 1a-6a with FeCl3 shows drastic changes of spectroscopic properties due to
      intramolecular and intermolecular pi-pi interactions. Doping of 1a-3a with iodine
      forms semiconductor due to its pi-donor properties and pi-pi stacking ability. X
      ray analysis of 1a confirmed a round, planar structure with nanoscale inner
      cavity, and revealed host ability for alkanes and unique packing structure.
      Interestingly, 2a and 3a self-aggregate in the solid state to form "molecular
      wires," which are about 200 nm thick and more than 1 mm long. The internal
      structures of fibrous aggregates have been investigated by optical microscope,
      scanning electron microscopy, atomic force microscopy, and X-ray diffraction
      analyses.

PMID- 17177425
TI  - Driven evolution of a constitutional dynamic library of molecular helices toward
      the selective generation of [2 x 2] gridlike arrays under the pressure of metal
      ion coordination.
AB  - Constitutional dynamics, self-assembly, and helical-folding control are brought
      together in the efficient Sc(OTf)3/microwave-catalyzed transimination of helical
      oligohydrazone strands, yielding highly diverse dynamic libraries of
      interconverting constituents through assembly, dissociation, and exchange of
      components. The transimination-type mechanism of the ScIII-promoted exchange, as
      well as its regioselectivity, occurring only at the extremities of the helical
      strands, allow one to perform directional terminal
      polymerization/depolymerization processes when starting with dissymmetric
      strands. A particular library is subsequently brought to express quantitatively
      [2 x 2] gridlike metallosupramolecular arrays in the presence of ZnII ions by
      component recombination generating the correct ligand from the dynamic set of
      interconverting strands. This behavior represents a process of driven evolution
      of a constitutional dynamic chemical system under the pressure (coordination
      interaction) of an external effector (metal ions).

PMID- 17177426
TI  - Coordination environment of a site-bound metal ion in the hammerhead ribozyme
      determined by 15N and 2H ESEEM spectroscopy.
AB  - Although site-bound Mg2+ ions have been proposed to influence RNA structure and
      function, establishing the molecular properties of such sites has been
      challenging due largely to the unique electrostatic properties of the RNA
      biopolymer. We have previously determined that, in solution, the hammerhead
      ribozyme (a self-cleaving RNA) has a high-affinity metal ion binding site
      characterized by a K(d,app) < 10 microM for Mn2+ in 1 M NaCl and speculated that
      this site has functional importance in the ribozyme cleavage reaction. Here we
      determine both the precise location and the hydration level of Mn2+ in this site
      using ESEEM (electron spin-echo envelope modulation) spectroscopy. Definitive
      assignment of the high-affinity site to the activity-sensitive A9/G10.1 region is
      achieved by site-specific labeling of G10.1 with 15N guanine. The coordinated
      metal ion retains four water ligands as measured by 2H ESEEM spectroscopy. The
      results presented here show that a functionally important, specific metal binding
      site is uniquely populated in the hammerhead ribozyme even in a background of
      high ionic strength. Although it has a relatively high thermodynamic affinity,
      this ion remains partially hydrated and is chelated to the RNA by just two
      ligands.

PMID- 17177428
TI  - Model for proton transport coupled to protein conformational change: application
      to proton pumping in the bacteriorhodopsin photocycle.
AB  - A modeling method is presented for protein systems in which proton transport is
      coupled to conformational change, as in proton pumps and in motors driven by the
      proton-motive force. Previously developed methods for calculating pKa values in
      proteins using a macroscopic dielectric model are extended beyond the equilibrium
      case to a master-equation model for the time evolution of the system through
      states defined by ionization microstate and a discrete set of conformers. The
      macroscopic dielectric model supplies free energy changes for changes of
      protonation microstate, while the method for obtaining the energetics of
      conformational change and the relaxation rates, the other ingredients needed for
      the master equation, are system dependent. The method is applied to the
      photoactivated proton pump, bacteriorhodopsin, using conformational free energy
      differences from experiment and treating relaxation rates through three
      adjustable parameters. The model is found to pump protons with an efficiency
      relatively insensitive to parameter choice over a wide range of parameter values,
      and most of the main features of the known photocycle from very early M to the
      return to the resting state are reproduced. The boundaries of these parameter
      ranges are such that short-range proton transfers are faster than longer-range
      ones, which in turn are faster than conformational changes. No relaxation rates
      depend on conformation. The results suggest that an "accessibility switch", while
      not ruled out, is not required and that vectorial proton transport can be
      achieved through the coupling of the energetics of ionization and conformational
      states.

PMID- 17177427
TI  - Carbohydrate amino acids: the intrinsic conformational preference for a beta-turn
      type structure in a carbopeptoid building block.
AB  - Infrared ion-dip spectroscopy coupled with DFT and ab initio calculations are
      used to establish the intrinsic conformational preference of the basic structural
      unit of a peptide mimic, a cis-tetrahydrofuran-based "carbopeptoid" (amide-sugar
      amide), isolated at low temperature in the gas phase. The carbopeptoid units form
      a beta-turn-type structure, stabilized by an intramolecular NH --> O=C hydrogen
      bond across the sugar ring, thus forming a 10-membered, C10 turn. Despite the
      clear preference for C10 beta-turn structures in the basic unit, however, the
      presence of multiple hydrogen-bond donating and accepting groups also generates a
      rich conformational landscape, and alternative structures may be populated in
      related molecules. Calculations on an extended, carbopeptoid dimer unit, which
      includes an alternating amide-sugar-amide-sugar-amide chain, identify conformers
      exhibiting alternative hydrogen-bonding arrangements that are somewhat more
      stable than the lowest-energy double beta-turn forming conformer.

PMID- 17177429
TI  - Electronic switching of single silicon atoms by molecular field effects.
AB  - We have observed on-off switching of scanning tunneling microscope current flow
      to silicon adatoms of the Si(111)-(7 x 7) surface that are enclosed within a
      bistable dimeric corral of self-assembled chlorododecane molecules. These
      thermally activated oscillations amounted to an order of magnitude change in the
      current. Theory showed that small changes in molecular configuration could cause
      alterations in the corralled adatom's electronic energy by as much as 1 eV due to
      local field effects, accounting for the observed current switching.

PMID- 17177430
TI  - Hsc70 ATPase: an insight into water dissociation and joint catalytic role of K+
      and Mg2+ metal cations in the hydrolysis reaction.
AB  - Hybrid quantum mechanics/molecular mechanics simulations, coupled to the recently
      introduced metadynamics method, performed on the adenosine triphosphate (ATP) of
      the bovine Hsc70 ATPase protein, show which specific water molecule of the
      solvation shell of the Mg2+ metal cation acts as a trigger in the initial phase
      of the ATP hydrolysis reaction in ATP synthase. Furthermore, we provide a
      detailed picture of the reaction mechanism, not accessible to experimental
      probes, that allows us to address two important issues not yet unraveled: (i) the
      pathway followed by a proton and a hydroxyl anion, produced upon dissociation of
      a putative catalytic H2O molecule, that is crucial in the selection of the
      reaction channel leading to the hydrolysis; (ii) the unique and cooperative role
      of K+ and Mg2+ metal ions in the reaction, acting as co-catalysts and promoting
      the release of the inorganic phosphate via an exchange of the OH- hydroxyl anion
      between their respective solvation shells. This is deeply different from the
      proton wire mechanism evidenced, for instance, in actin and lowers significantly
      the free energy barrier of the reaction.

PMID- 17177432
TI  - Methyaluminoxane (MAO) polymerization mechanism and kinetic model from ab initio
      molecular dynamics and electronic structure calculations.
AB  - MAO is the co-catalyst in metallocene catalytic systems, which are widely used in
      single-site olefin polymerization due to their high stereoselectivity. To date,
      the structures of the catalytically active compound or compounds in MAO have
      eluded researchers. Although many structural models have been proposed, none are
      generally accepted. In this study, aspects of the formation mechanism of MAO are
      addressed. Molecular dynamics simulations at the MP2 level of theory were carried
      out for presumed elementary steps in MAO formation via hydrolysis of
      trimethylaluminum (TMA). Methane production was observed, in agreement with
      experiment, as well as intermediate species that are consistent with the known
      structural features of MAO and similar to isolated and structurally characterized
      aluminoxanes. A (CH3)3Al-OH2 species, which we denote as TMA-OH2, containing a
      stable Al-O single bond emerged as the building block molecule. From this
      species, a hexameric cage was formed and activation barriers for the various
      reactions were calculated. Three distinct channels were identified for growth
      beyond the hexameric cage. It was concluded that MAO formation is a step
      polymerization through a bifunctional monomer, with [(CH3)Al-O] as the structural
      unit and a kinetic model was proposed. The structures that emerged were in
      agreement with the crystallographic evidence for aluminoxanes and support the
      experimental data regarding the MAO chemical composition.

PMID- 17177431
TI  - Electrochemical investigations of the interconversions between catalytic and
      inhibited states of the [FeFe]-hydrogenase from Desulfovibrio desulfuricans.
AB  - Studies of the catalytic properties of the [FeFe]-hydrogenase from Desulfovibrio
      desulfuricans by protein film voltammetry, under a H2 atmosphere, reveal and
      establish a variety of interesting properties not observed or measured
      quantitatively with other techniques. The catalytic bias (inherent ability to
      oxidize hydrogen vs reduce protons) is quantified over a wide pH range: the
      enzyme is proficient at both H2 oxidation (from pH > 6) and H2 production (pH <
      6). Hydrogen production is inhibited by H2, but the effect is much smaller than
      observed for [NiFe]-hydrogenases from Allochromatium vinosum or Desulfovibrio
      fructosovorans. Under anaerobic conditions and positive potentials, the [FeFe]
      hydrogenase is oxidized to an inactive form, inert toward reaction with CO and
      O2, that rapidly reactivates upon one-electron reduction under 1 bar of H2. The
      potential dependence of this interconversion shows that the oxidized inactive
      form exists in two pH-interconvertible states with pK(ox) = 5.9. Studies of the
      CO-inhibited enzyme under H2 reveals a strong enhancement of the rate of
      activation by white light at -109 mV (monitoring H2 oxidation) that is absent at
      low potential (-540 mV, monitoring H+ reduction), thus demonstrating
      photolability that is dependent upon the oxidation state.

PMID- 17177433
TI  - Influence of single-walled carbon nanotubes induced crystallinity enhancement and
      morphology change on polymer photovoltaic devices.
AB  - Single-walled carbon nanotubes (SWNTs) were determined to have significant
      interaction with poly(3-hexylthiophene) (P3HT), which is helpful to form
      continuous active film with interpenetrating structure and improve the
      crystallinity of the resultant film for SWNTs/P3HT composite. Photovoltaic
      devices based on an active film with relatively higher crystallinity display much
      enhanced performance. The work function of carbon nanotubes modulated by electron
      transferring from P3HT to SWNTs is proposed to explain the high open-circuit
      voltage (V(OC)) obtained from the photovoltaic devices based on the SWNTs/P3HT
      system.

PMID- 17177435
TI  - Adsorption of molecular hydrogen on coordinatively unsaturated Ni(II) sites in a
      nanoporous hybrid material.
AB  - A porous hybrid inorganic/organic material, NaNi3(OH)(SIP)2 [SIP = 5
      sulfoisophthalate][1], is shown to strongly bind molecular hydrogen at
      coordinatively unsaturated metal sites. A combination of H2 sorption isotherms,
      temperature programmed desorption, and inelastic neutron scattering spectroscopy
      show the existence of a considerable number of such strong binding sites in [1]
      along with other sites where hydrogen is more weakly physisorbed. The overall
      capacity for hydrogen of this material as well as the much stronger binding of
      hydrogen than in typical porous material represent an important step toward a
      possible utilization of porous media for hydrogen storage.

PMID- 17177436
TI  - A theoretical analysis of rate constants and kinetic isotope effects
      corresponding to different reactant valleys in lactate dehydrogenase.
AB  - In some enzymatic systems large conformational changes are coupled to the
      chemical step, in such a way that dispersion of rate constants can be observed in
      single-molecule experiments, each corresponding to the reaction from a different
      reactant valley. Under this perspective here we present a computational study of
      pyruvate to lactate transformation catalyzed by lactate dehydrogenase. The
      reaction consists of a hydride transfer and a proton transfer that seem to take
      place concertedly. The degree of asynchronicity and the energy barrier depend on
      the particular starting reactant valley. In order to estimate rate constants we
      used a free energy perturbation technique adapted to follow the intrinsic
      reaction coordinate for several possible reaction paths. Tunneling effects are
      also obtained with a slightly modified version of the ensemble-averaged
      variational transition state theory with multidimensional tunneling
      contributions. According to our results the closure of the active site by means
      of a flexible loop can lead to the formation of different reactant complexes
      displaying different features in the disposition of some key residues (such as
      Arg109), interactions with the substrate and number of water molecules in the
      active site. The chemical step of the reaction takes place with a different
      reaction rate from each of these complexes. Finally, primary kinetic isotope
      effects for replacement of the transferring hydrogen of the cofactor with a
      deuteride are in good agreement with experimental observations, thus validating
      our methodology.

PMID- 17177434
TI  - Differential sensing of protein influences by NO and CO vibrations in heme
      adducts.
AB  - Heme proteins bind the gaseous ligands XO (X = C, N, O) via backbonding from Fe
      d(pi) electrons. Backbonding is modulated by distal interactions of the bound
      ligand with the surrounding protein and by variations in the strength of the
      trans proximal ligand. Vibrational modes associated with FeX and XO bond
      stretching coordinates report on these interactions, but the interpretive
      framework developed for CO adducts, involving anticorrelations of nuFeC and nuCO,
      has seemed not to apply to NO adducts. We have now obtained an excellent
      anticorrelation of nuFeN and nuNO, via resonance Raman spectroscopy on (N
      methylimidazole)Fe(II)TPP-Y(NO), where TPP-Y is tetraphenylporphine with electron
      donating or -withdrawing substituents, Y, that modulate the backbonding; the
      problem of laser-induced dissociation of the axial base was circumvented by using
      frozen solutions. New data are also reported for CO adducts. The anticorrelations
      are supported by DFT calculations of structures and spectra. When protein data
      are examined, the NO adducts show large deviations from the modeled
      anticorrelation when there are distal H-bonds or positive charges. These
      deviations are proposed to result from closing of the FeNO angle due to a shift
      in the valence isomer equilibrium toward the Fe(III)(NO-) form, an effect that is
      absent in CO adducts. The differing vibrational patterns of CO and NO adducts
      provide complementary information with respect to protein interactions, which may
      help to elucidate the mechanisms of ligand discrimination and signaling in heme
      sensor proteins.

PMID- 17177438
TI  - Hydrogen storage in a microporous metal-organic framework with exposed Mn2+
      coordination sites.
AB  - Use of the tritopic bridging ligand 1,3,5-benzenetristetrazolate (BTT3-) enables
      formation of [Mn(DMF)6]3[(Mn4Cl)3(BTT)8(H2O)12]2.42DMF.11H2O.20CH3OH, featuring a
      porous metal-organic framework with a previously unknown cubic topology. Crystals
      of the compound remain intact upon desolvation and show a total H2 uptake of 6.9
      wt % at 77 K and 90 bar, which at 60 g H2/L provides a storage density 85% of
      that of liquid hydrogen. The material exhibits a maximum isosteric heat of
      adsorption of 10.1 kJ/mol, the highest yet observed for a metal-organic
      framework. Neutron powder diffraction data demonstrate that this is directly
      related to H2 binding at coordinatively unsaturated Mn2+ centers within the
      framework.

PMID- 17177437
TI  - Dissecting and reducing the heterogeneity of excited-state energy transport in
      DNA-based photonic wires.
AB  - Molecular photonic wires are one-dimensional representatives of a family of
      nanoscale molecular devices that transport excited-state energy over considerable
      distances in analogy to optical waveguides in the far-field. In particular, the
      design and synthesis of such complex supramolecular devices is challenging
      concerning the desired homogeneity of energy transport. On the other hand, novel
      optical techniques are available that permit direct investigation of
      heterogeneity by studying one device at a time. In this article, we describe our
      efforts to synthesize and study DNA-based molecular photonic wires that carry
      several chromophores arranged in an energetic downhill cascade and exploit
      fluorescence resonance energy transfer to convey excited-state energy. The focus
      of this work is to understand and control the heterogeneity of such complex
      systems, applying single-molecule fluorescence spectroscopy (SMFS) to dissect the
      different sources of heterogeneity, i.e., chemical heterogeneity and
      inhomogeneous broadening induced by the nanoenvironment. We demonstrate that the
      homogeneity of excited-state energy transport in DNA-based photonic wires is
      dramatically improved by immobilizing photonic wires in aqueous solution without
      perturbation by the surface. In addition, our study shows that the in situ
      construction of wire molecules, i.e., the stepwise hybridization of differently
      labeled oligonucleotides on glass cover slides, further decreases the observed
      heterogeneity in overall energy-transfer efficiency. The developed strategy
      enables efficient energy transfer between up to five chromophores in the majority
      of molecules investigated along a distance of approximately 14 nm. Finally, we
      used multiparameter SMFS to analyze the energy flow in photonic wires in more
      detail and to assign residual heterogeneity under optimized conditions in
      solution to different leakages and competing energy-transfer processes.

PMID- 17177439
TI  - Chemical grafting of biphenyl self-assembled monolayers on ultrananocrystalline
      diamond.
AB  - We have investigated the formation of self-assembled monolayers (SAMs) of 4'
      nitro-1,1-biphenyl-4-diazonium tetrafluoroborate (NBD) onto ultrananocrystalline
      diamond (UNCD) thin films. In contrast to the common approach to modify diamond
      and diamond-like substrates by electrografting, the SAM was formed from the
      saturated solution of NBD in acetonitrile by pure chemical grafting. Atomic force
      microscopy (AFM), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry
      (CV), and near edge X-ray absorption fine structure spectroscopy (NEXAFS) have
      been used to verify the direct covalent attachment of the 4'-nitro-1,1-biphenyl
      (NB) SAM on the diamond substrate via stable C-C bonds and to estimate the
      monolayer packing density. The results confirm the presence of a very stable,
      homogeneous and dense monolayer. Additionally, the terminal nitro group of the NB
      SAM can be readily converted into an amino group by X-ray irradiation as well as
      electrochemistry. This opens the possibility of in situ electrochemical
      modification as well as the creation of chemical patterns (chemical lithography)
      in the SAM on UNCD substrates and enables a variety of consecutive chemical
      functionalization for sensing and molecular electronics applications.

PMID- 17177442
TI  - Synthesis, properties, and reactions of a series of stable dialkyl-substituted
      silicon-chalcogen doubly bonded compounds.
AB  - The first dialkyl-substituted silicon-chalcogen doubly bonded compounds [R2Si=X;
      R2=1,1,4,4-tetrakis(trimethylsilyl)butane-1,4-diyl, X = S (4), Se (5), and Te
      (6)]were synthesized by the reactions of an isolable dialkylsilylene R2Si: (3)
      with phosphine sulfide, elemental selenium, and elemental tellurium,
      respectively. Systematic changes of characteristics of silicon-chalcogen double
      bonds are elucidated by X-ray analysis, UV-vis spectroscopy, and DFT
      calculations. In the solid state, the unsaturated silicon atom in 4-6 adopts
      planar geometry and the extent of the shortening of Si=X double bonds from the
      corresponding Si-X single bonds decreases in the order 4 > 5 > 6. In the
      absorption spectra of 4-6, pi -->pi* transition bands are observed distinctly in
      addition to n -->pi* transition bands. Both the n -->pi* and pi -->pi*
      transitions are red-shifted in the order 4 < 5 < 6, and the difference between
      the energies of the two transitions is kept almost constant among 4-6. The
      tendency is explained using the qualitative perturbation theory and is reproduced
      by the DFT calculations for model silanechalcogenones. Addition reactions of
      water, methanol, and isoprene to 4-6 are reported.

PMID- 17177441
TI  - Elucidation of hydrolysis mechanisms for fatty acid amide hydrolase and its
      Lys142Ala variant via QM/MM simulations.
AB  - Fatty acid amide hydrolase (FAAH) is a serine hydrolase that degrades anandamide,
      an endocannabinoid, and oleamide, a sleep-inducing lipid, and has potential
      applications as a therapeutic target for neurological disorders. Remarkably, FAAH
      hydrolyzes amides and esters with similar rates; however, the normal preference
      for esters reemerges when Lys142 is mutated to alanine. To elucidate the
      hydrolysis mechanisms and the causes behind this variation of selectivity, mixed
      quantum and molecular mechanics (QM/MM) calculations were carried out to obtain
      free-energy profiles for alternative mechanisms for the enzymatic hydrolyses. The
      methodology features free-energy perturbation calculations in Monte Carlo
      simulations with PDDG/PM3 as the QM method. For wild-type FAAH, the results
      support a mechanism, which features proton transfer from Ser217 to Lys142,
      simultaneous proton transfer from Ser241 to Ser217, and attack of Ser241 on the
      substrate's carbonyl carbon to yield a tetrahedral intermediate, which
      subsequently undergoes elimination with simultaneous protonation of the leaving
      group by a Lys142-Ser217 proton shuttle. For the Lys142Ala mutant, a striking
      multistep sequence is proposed with simultaneous proton transfer from Ser241 to
      Ser217, attack of Ser241 on the carbonyl carbon of the substrate, and elimination
      of the leaving group and its protonation by Ser217. Support comes from the free
      energy results, which well reproduce the observation that the Lys142Ala mutation
      in FAAH decreases the rate of hydrolysis for oleamide significantly more than for
      methyl oleate.

PMID- 17177443
TI  - Catalytic mechanism of glycosyltransferases: hybrid quantum mechanical/molecular
      mechanical study of the inverting N-acetylglucosaminyltransferase I.
AB  - The Golgi glycosyltransferase, N-acetylglucosaminyltransferase I (GnT-I),
      catalyzes the transfer of a GlcNAc residue from the donor UDP-GlcNAc to the C2
      hydroxyl group of a mannose residue in the trimannosyl core of the Man5GlcNAc2
      Asn-X oligosaccharide. The catalytic mechanism of GnT-I was investigated using a
      hybrid quantum mechanical/molecular mechanical (QM/MM) method with a QM part
      containing 88 atoms treated with density functional theory (DFT) at the BP/TZP
      level. The remaining parts of a GnT-I complex, altogether 5633 atoms, were
      modeled using the AMBER molecular force field. A theoretical model of a Michaelis
      complex was built using the X-ray structure of GnT-I in complex with the donor
      having geometrical features consistent with kinetic studies. The QM(DFT)/MM model
      identified a concerted SN2-type of transition state with D291 as the catalytic
      base for the reaction in the enzyme active site. The TS model features nearly
      simultaneous nucleophilic addition and dissociation steps accompanied by the
      transfer of the nucleophile proton Hb2 to the catalytic base D291. The structure
      of the TS model is characterized by the Ob2-C1 and C1-O1 bond distances of 1.912
      and 2.542 A, respectively. The activation energy for the proposed reaction
      mechanism was estimated to be approximately 19 kcal mol-1. The calculated alpha
      deuterium kinetic isotope effect of 1.060 is consistent with the proposed
      reaction mechanism. Theoretical results also identified interactions between the
      Hb6 and beta-phosphate oxygen of the UDP and a low-barrier hydrogen bond between
      the nucleophile and the catalytic base D291. It is proposed that these
      interactions contribute to a stabilization of TS. This modeling study provided
      detailed insight into the mechanism of the GlcNAc transfer catalyzed by GnT-I,
      which is the first step in the conversion of high mannose oligosaccharides to
      complex and hybrid N-glycan structures.

PMID- 17177440
TI  - Coupling molecular beacons to barcoded metal nanowires for multiplexed, sealed
      chamber DNA bioassays.
AB  - We have combined molecular beacon (MB) probes with barcoded metal nanowires to
      enable no-wash, sealed chamber, multiplexed detection of nucleic acids. Probe
      design and experimental parameters important in nanowire-based MB assays are
      discussed. Loop regions of 24 bases and 5 base pair stem regions in the beacon
      probes gave optimal performance. Our results suggest that thermodynamic
      predictions for secondary structure stability of solution-phase MB can guide
      probe design for nanowire-based assays. Dengue virus-specific probes with
      predicted solution-phase DeltaG of folding in 500 mM buffered NaCl of
      approximately -4 kcal/mol performed better than those with DeltaG > -2 or < -6
      kcal/mol. Buffered 300-500 mM NaCl was selected after comparison of several
      buffers previously reported for similar types of assays, and 200-500 mM NaCl was
      found to be the optimal ionic strength for the hybridization temperatures (25 and
      50 degrees C) and probe designs used here. Target binding to the surface as a
      function of solution concentration fit a Sips isotherm with Kd = 1.7 +/- 0.3 nM.
      The detection limit was approximately 100 pM, limited by incomplete quenching.
      Single base mismatches could be discriminated from fully complementary targets.
      Oligonucleotide target sequences specific for human immunodeficiency, hepatitis
      C, and severe acute respiratory viruses were assayed simultaneously in a no-wash,
      sealed chamber, multiplexed experiment in which each of three probe sequences was
      attached to a different pattern of encoded nanowires. Finally, we demonstrated
      that probe-coated nanowires retain their selectivity and sensitivity in a
      triplexed assay after storage for over 3 months.

PMID- 17177444
TI  - Self-organization of polybases neutralized with mesogenic wedge-shaped sulfonic
      acid molecules: an approach toward supramolecular cylinders.
AB  - Complexes consisting of poly(4-vinylpyridine) and mesogenic wedge-shaped ligands
      4'-[3",4",5"-tris(dodecyloxy)benzoyloxy]azobenzene-4-sulfonic acid and 4'
      [3",4",5"-tris(octyloxy)benzoyloxy]azobenzene-4-sulfonic acid have been prepared
      with different monomer/ligand ratios. Upon protonation of the poly(4
      vinylpyridine) chains by the wedge-shaped sulfonic acid molecules a hypsochromic
      and hyperchromic effect was observed with the pi-pi* transition of the azo
      chromophor, allowing us to monitor the neutralization process by means of UV-vis
      spectroscopy in solution. The changes of the absorption characteristics implied a
      conformational change of the polymer backbone. In the bulk the interaction
      between pyridine and sulfonic acid moieties was proved by FT-IR spectroscopy.
      Polarizing optical microscopy, differential scanning calorimetry, and X-ray
      diffraction measurements were used to study the bulk structure of the complexes.
      The complexes formed a liquid crystalline lamellar phase at low degrees of
      substitution, while a hexagonal columnar mesophase was observed at degrees of
      neutralization of 80% and higher.

PMID- 17177445
TI  - Microsolvation effects on the excited-state dynamics of protonated tryptophan.
AB  - To better understand the complex photophysics of the amino acid tryptophan, which
      is widely used as a probe of protein structure and dynamics, we have measured
      electronic spectra of protonated, gas-phase tryptophan solvated with a controlled
      number of water molecules and cooled to approximately 10 K. We observe that, even
      at this temperature, the bare molecule exhibits a broad electronic spectrum,
      implying ultrafast, nonradiative decay of the excited state. Surprisingly, the
      addition of two water molecules sufficiently lengthens the excited-state lifetime
      that we obtain a fully vibrationally resolved electronic spectrum. Quantum
      chemical calculations at the RI-CC2/aug-cc-pVDZ level, together with TDDFT/pw
      based first-principles MD simulations of the excited-state dynamics, clearly
      demonstrate how interactions with water destabilize the photodissociative states
      and increase the excited-state lifetime.

PMID- 17177446
TI  - Efficient intramolecular general acid catalysis of nucleophilic attack on a
      phosphodiester.
AB  - The hydrolysis of methyl 8-dimethylamino-1-naphthyl phosphate 4 and its reactions
      with a representative range of nucleophiles are catalyzed by the dimethylammonium
      group at acidic pH with rate accelerations of the order of 106. The reaction
      persists up to pH 7 because the strong intramolecular hydrogen bond, which is the
      key to efficient general acid catalysis, is present also in the reactant. The
      sensitivity to the basicity of the nucleophile (Bronsted beta(nuc) = 0.29) lies
      between values measured previously for mono- and triesters. The comparisons
      suggest that general acid catalyzed reactions of phosphate mono- or diesters with
      strongly basic oxyanion nucleophiles (like those derived from a serine oxygen or
      a bound water molecule in an enzyme active site) will be fastest when their
      negative charges are neutralized by protonation. Reactions with NH2OH and its N
      methylated derivatives show an apparent alpha-effect, but NH2OMe reacts no faster
      than a primary amine of similar basicity. It is suggested that the reaction
      involving NH2OH as an oxygen nucleophile proceeds through the pre-equilibrium
      formation of the tautomer H3N+-O- as the active nucleophile: ab initio
      calculations support this idea.

PMID- 17177448
TI  - Mechanism of catalytic aziridination with manganese corrole: the often postulated
      high-valent Mn(V) imido is not the group transfer reagent.
AB  - The reaction of Arl=NTs (Ar = 2-(tert-butylsulfonyl)benzene and Ts = p
      toluenesulfonyl) and (tpfc)Mn (tpfc=5,10,15-tris(pentafluorophenyl)corrole), 1,
      affords the high-valent (tpfc)MnV=NTs, 2, on stopped-flow time scale. The
      reaction proceeds via the adduct [(tpfc)MnIII(ArINTs)], 3, with formation
      constant K3 = (10 +/- 2) x 10(3) L mol-1. Subsequently, 3 undergoes unimolecular
      group transfer to give complex 2 with the rate constant k4 = 0.26 +/- 0.07 s-1 at
      24.0 degrees C. The complex (tpfc)Mn catalyzes [NTs] group transfer from ArINTs
      to styrene substrates with low catalyst loading and without requirement of excess
      olefin. The catalytic aziridination reaction is most efficient in benzene because
      solvents such as toluene undergo a competing hydrogen atom transfer (HAT)
      reaction resulting in H2NTs and lowered aziridine yields. The high-valent
      manganese imido complex (tpfc)Mn=NTs does not transfer its [NTs] group to
      styrene. Double-labeling experiments with ArINTs and ArINTstBu (TstBu = (p-tert
      butylphenyl)sulfonyl) establish the source of [NR] transfer as a "third oxidant",
      which is an adduct of Mn(V) imido, [(tpfc)Mn(NTstBu)(ArINTs)](4). Formation of
      this oxidant is rate limiting in catalysis.

PMID- 17177447
TI  - Seeded growth of asymmetric binary nanocrystals made of a semiconductor TiO2
      rodlike section and a magnetic gamma-Fe2O3 spherical domain.
AB  - Asymmetric binary nanocrystals (BNCs), comprising one c-axis elongated anatase
      TiO2 section and one gamma-Fe2O3 spherical domain attached together, are
      synthesized by heterogeneous nucleation of iron oxide onto the longitudinal
      facets of TiO2 nanorods in a ternary surfactant mixture. The topologically
      controlled composition of the BNCs is ascertained by a combination of powder X
      ray diffraction, Raman and Mossbauer spectroscopy, high-angle annular dark-field
      imaging, and high-resolution transmission electron microscopy lattice fringe
      mapping, while their size-dependent magnetic behavior is demonstrated by ac
      susceptibility measurements. The heteroepitaxial growth proceeds through a
      mechanism never observed before for colloidal nanoheterostructures: the two
      domains share a restricted and locally curved junction region, which accommodates
      efficiently the interfacial strain and retards the formation of misfit
      dislocations. It is believed that these BNCs, which combine the properties of two
      technologically relevant oxide materials, can pave the way to reinforced
      applications in several fields of nanoscience, such as in photocatalysis, in
      malignant cell treatments, and in nanocrystal assembly.

PMID- 17177449
TI  - Diastereomeric Xe chemical shifts in tethered cryptophane cages.
AB  - Cryptophane cages serve as host molecules to a Xe atom. Functionalization of
      cryptophane-A has permitted the development of Xe as a biosensor. Synthetic
      routes used to prepare cryptophanes result in racemic mixtures of the chiral
      cages. In the preparation of a tethered cryptophane-A cage for biosensor
      applications, some achiral and chiral substituents such as left-handed amino
      acids have been used. When the substituent is achiral, the NMR signal of the Xe
      atom in the functionalized cage in solution is a single isotropic peak, since the
      Xe shielding tensor components in the R and L cages differ by no more than the
      signs of the off-diagonal elements. Chiral substituents can split the cage
      encapsulated Xe NMR signal into one or more sets of doublets, depending on the
      number of asymmetric centers in the substituent. We carry out quantum mechanical
      calculations of Xe nuclear magnetic shielding for the Xe atom at the same
      strategic position within an L cryptophane-A cage, under the influence of chiral
      potentials that represent r or l substituents outside the cage. Calculations of
      the Xe shielding response in the Lr and Ll diastereomeric pairs permit the
      prediction of the relative order of the Xe chemical shifts in solutions
      containing the Rl and Ll diastereomers. Where the substituent itself possesses
      two chiral centers, comparison of the calculated isotropic shielding responses in
      the Llr, Lrl, Rll, and Lrr systems, respectively, permits the prediction of the
      Xe spectrum of diastereomeric systems in solutions containing Llr, Rlr, Lll, and
      Rll systems. Assignment of the peaks observed in the experimental Xe NMR spectra
      is therefore possible, without having to undertake the difficult synthetic route
      that produces a single optically pure enantiomer.

PMID- 17177451
TI  - Exploring the actinide-actinide bond: theoretical studies of the chemical bond in
      Ac2, Th2, Pa2, and U2.
AB  - Multiconfigurational quantum chemical methods (CASSCF/CASPT2) have been used to
      study the chemical bond in the actinide diatoms Ac2, Th2, Pa2, and U2. Scalar
      relativistic effects and spin-orbit coupling have been included in the
      calculations. In the Ac2 and Th2 diatoms the atomic 6d, 7s, and 7p orbitals are
      the significant contributors to the bond, while for the two heavier diatoms, the
      5f orbitals become increasingly important. Ac2 is characterized by a double bond
      with a 3Sigmag-(0g+) ground state, a bond distance of 3.64. A, and a bond energy
      of 1.19 eV. Th2 has quadruple bond character with a 3Dg(1g) ground state. The
      bond distance is 2.76 A and the bond energy (D0) 3.28 eV. Pa2 is characterized by
      a quintuple bond with a 3Sigmag-(0g+) ground state. The bond distance is 2.37 A
      and the bond energy 4.00 eV. The uranium diatom has also a quintuple bond with a
      7Og (8g) ground state, a bond distance of 2.43 A, and a bond energy of 1.15 eV.
      It is concluded that the strongest bound actinide diatom is Pa2, characterized by
      a well-developed quintuple bond.

PMID- 17177450
TI  - Total synthesis, structure revision, and absolute configuration of (-)-brevenal.
AB  - Total synthesis of structure 1 originally proposed for brevenal, a nontoxic
      polycyclic ether natural product isolated from the Florida red tide
      dinoflagellate, Karenia brevis, was accomplished. The key features of the
      synthesis involved (i) convergent assembly of the pentacyclic polyether skeleton
      based on our developed Suzuki-Miyaura coupling chemistry and (ii) stereoselective
      construction of the multi-substituted (E,E)-dienal side chain by using copper(I)
      thiophen-2-carboxylate (CuTC)-promoted modified Stille coupling. The disparity of
      NMR spectra between the synthetic material and the natural product required a
      revision of the proposed structure. Detailed spectroscopic comparison of
      synthetic 1 with natural brevenal, coupled with the postulated biosynthetic
      pathway for marine polyether natural products, suggested that the natural product
      was most likely represented by 2, the C26 epimer of the proposed structure 1. The
      revised structure was finally validated by completing the first total synthesis
      of (-)-2, which also unambiguously established the absolute configuration of the
      natural product.

PMID- 17177452
TI  - High-resolution electronic spectra of ethylenedioxythiophene oligomers.
AB  - The photophysical properties of a series of 3,4-ethylenedioxythiophene oligomers
      (OEDOT) with up to five repeat units are studied as function of conjugation
      length using absorption, fluorescence, phosphorescence, and triplet-triplet
      absorption spectroscopy at low temperature in a rigid matrix. At 80 K, a
      remarkably highly resolved vibrational fine structure can be observed in the all
      electronic spectra which reveals that the electronic structure of the oligomers
      strongly couples to two different vibrational modes (approximately 180 and
      approximately 50 meV). The energies of the 0-0 transitions in absorption, and
      fluorescence, phosphorescence, and triplet-triplet absorption all show a
      reciprocal dependence on the inverse number of repeat units. The triplet energies
      inferred from the phosphorescence spectra are accurately reproduced by quantum
      chemical DFT calculations using optimized geometries for the singlet ground state
      (S0) and first excited triplet state (T1). Using vibrational IR and Raman
      spectroscopy and quantum chemical DFT calculations for the normal modes in the
      ground state, we have been able to assign the vibrations that couple to the
      electronic structure to fully symmetric normal modes. The high-energy mode is
      associated with the well-known carbon-carbon bond stretch vibration, and the low
      energy mode involves a deformation of the bond angles within the thiophene rings
      and a change of C-S bond lengths. Experimentally obtained Huang-Rhys parameters
      and theoretical normal mode deformations are used to analyze the geometry changes
      between T1 and S0 and to semiexperimentally predict the geometry in the S1 state
      for 2EDOT.

PMID- 17177453
TI  - Glyoxalase I-type hemithioacetal isomerization reactivity of a mononuclear Ni(II)
      deprotonated amide complex.
AB  - The synthesis, characterization, and hemithioacetal isomerization reactivity of a
      mononuclear Ni(II) deprotonated amide complex, [(bppppa-)Ni]ClO4.CH3OH (1, bppppa
      = monoanion of N,N-bis-[(6-phenyl-2-pyridyl)methyl]-N-[(6-pivaloylamido-2
      pyridyl)methyl]amine), are reported. Complex 1 was characterized by X-ray
      crystallography, 1H NMR, UV-vis, FTIR, and elemental analysis. Treatment of 1
      with an equimolar amount of the hemithioacetal PhC(O)CH(OH)SCD3 in dry
      acetonitrile results in the production of the thioester PhCH(OH)C(O)SCD3 in
      approximately 60% yield. This reaction is conveniently monitored via 2H NMR
      spectroscopy. A protonated analogue of 1, [(bppppa)Ni](ClO4)2 (2), is unreactive
      with the hemithioacetal, thus indicating the requirement of the anionic chelate
      ligand in 1 for hemithioacetal isomerization reactivity. Complex 1 is unreactive
      with the thioester product, PhCH(OH)C(O)SCD3, which indicates that the pKa value
      for the PhCH(OH)C(O)SCD3 proton of the thioester must be significantly higher
      than the pKa value of the C-H proton of the hemithioacetal (PhC(O)CH(OH)SCD3).
      Complex 1 is the first well-characterized Ni(II) coordination complex to exhibit
      reactivity relevant to Ni(II)-containing E. coli glyoxalase I. Treatment of
      NiBr2.2H2O with PhC(O)CH(OH)SCD3 in the presence of 1-methylpyrrolidine also
      yields thioester product, albeit the reaction is slower and involves the
      formation of multiple -SCD3 labeled species, as detected by 2H NMR spectroscopy.
      The results of this study provide the first insight into hemithioacetal
      isomerization promoted by a synthetic Ni(II) coordination complex versus a simple
      Ni(II) ion.

PMID- 17177454
TI  - Expression of a supramolecular complex at a multivalent interface.
AB  - The multivalent binding of a supramolecular complex at a multivalent host surface
      by combining the orthogonal beta-cyclodextrin (CD) host-guest and metal ion
      ethylenediamine coordination motifs is described. As a heterotropic, divalent
      linker, an adamantyl-functionalized ethylenediamine derivative was used. This was
      complexed with Cu(II) or Ni(II). The binding of the complexes to a CD self
      assembled monolayer (SAM) was studied as a function of pH by means of surface
      plasmon resonance (SPR) spectroscopy. A heterotropic, multivalent binding model
      at interfaces was used to quantify the multivalent enhancement at the surface.
      The Cu(II) complex showed divalent binding to the CD surface with an enhancement
      factor higher than 100 relative to the formation of the corresponding divalent
      complex in solution. Similar behavior was observed for the Ni(II) system.
      Although the Ni(II) system could potentially be trivalent, only divalent binding
      was observed at the CD SAMs, which was confirmed by desorption experiments.

PMID- 17177455
TI  - Reduction of O2 to superoxide anion (O2.-) in water by heteropolytungstate
      cluster-anions.
AB  - Fundamental information concerning the mechanism of electron transfer from
      reduced heteropolytungstates (POM(red)) to O2, and the effect of donor-ion charge
      on reduction of O2 to superoxide anion (O2.-), is obtained using an isostructural
      series of 1e--reduced donors: alpha-X(n+)W12O40(9-n)-, X(n+) = Al3+, Si4+, P5+.
      For all three, a single rate expression is observed: -d[POM(red)]/dt =
      2k12[POM(red)][O2], where k12 is for the rate-limiting electron transfer from
      POM(red) to O2. At pH 2 (175 mM ionic strength), k12 increases from 1.4 +/- 0.2
      to 8.5 +/- 1 to 24 +/- 2 M-1s-1 as Xn+ is varied from P5+ (3red) to Si4+ (2red)
      to Al3+ (1red). Variable-pH data (for 1red) and solvent-kinetic isotope (KIE =
      kH/kD) data (all three ions) indicate that protonated superoxide (HO2.) is formed
      in two steps--electron transfer, followed by proton transfer (ET-PT mechanism-
      rather than via simultaneous proton-coupled electron transfer (PCET). Support for
      an outersphere mechanism is provided by agreement between experimental k12 values
      and those calculated using the Marcus cross relation. Further evidence is
      provided by the small variation in k12 observed when Xn+ is changed from P5+ to
      Si4+ to Al3+, and the driving force for formation of O2.- (aq), which increases
      as cluster-anion charge becomes more negative, increases by nearly +0.4 V (a
      decrease of >9 kcal mol-1 in DeltaG degrees ). The weak dependence of k12 on POM
      reduction potentials reflects the outersphere ET-PT mechanism: as the anions
      become more negatively charged, the "successor-complex" ion pairs are subject to
      larger anion-anion repulsions, in the order [(3(ox)3-)(O2.-)]4- < [(2(ox)4-)(O2.
      )]5- < [(1(ox)5-)(O2.-)]6-. This reveals an inherent limitation to the use of
      heteropolytungstate charge and reduction potential to control rates of electron
      transfer to O2 under turnover conditions in catalysis.

PMID- 17177456
TI  - Synthesis, structure, and resolution of exceptionally twisted pentacenes.
AB  - 9,10,11,20,21,22-hexaphenyltetrabenzo[a,c,l,n]pentacene (2) and a dimethyl
      derivative (2m) were prepared by the reaction of 1,3-diphenylphenanthro[9,10
      c]furan with bisaryne equivalents generated from 1,2,4,5-tetrabromo-3,6
      diarylbenzenes in the presence of n-butyllithium, followed by deoxygenation of
      the double adducts with low-valent titanium. Both are bright red solids with a
      strong orange fluorescence in solution. The X-ray structures of these compounds
      show them to be the most highly twisted polycyclic aromatic hydrocarbons known.
      Compound 2 has an end-to-end twist of 144 degrees , and the two
      crystallographically independent molecules of 2m have twists of 138 degrees and
      143 degrees. Both molecules were resolved by chromatography on chiral supports,
      and the pure enantiomers have extremely high specific rotations (for 2, [alpha]D
      = 7400 degrees; for 2m, 5600 degrees), but the molecules racemize slowly at room
      temperature (DeltaG++rac = 24 kcal/mol). Both the experimental geometry and the
      observed racemization barrier for 2 are in good agreement with computational
      studies of the molecule at a variety of levels. Attempts to prepare compound 2 by
      reaction of tetraphenylbenzyne with 9,10,12,13-tetraphenyl-11
      oxacyclopenta[b]triphenylene (3, a twisted isobenzofuran) gave no adducts, and
      attempts to prepare tetradecaphenylpentacene by reaction of
      hexaphenylisobenzofuran (11) with bisaryne equivalents gave only monoadducts.

PMID- 17177457
TI  - Asymmetric induction in hydrogen-mediated reductive aldol additions to alpha
      amino aldehydes catalyzed by rhodium: selective formation of syn-stereotriads
      directed by intramolecular hydrogen-bonding.
AB  - Rhodium-catalyzed hydrogenation of methyl vinyl ketone and ethyl vinyl ketone in
      the presence of N-Boc-alpha-aminoaldehydes 3a-8a at ambient temperature and
      pressure results in reductive C-C coupling to furnish aldol adducts 3b-8b and 3c
      8c, respectively, which incorporate stereotriads that embody high levels of syn
      aldol selectivity accompanied by high levels of anti-Felkin-Anh control. The
      collective data are consistent with a catalytic mechanism involving addition of
      the Z(O)-rhodium enolate to the sterically less-encumbered aldehyde pi-face of an
      intramolecularly hydrogen-bonded chelate through a Zimmerman-Traxler type
      transition structure. Stereochemical assignments are supported by single-crystal
      X-ray diffraction analysis of 5b-O-3,5-dinitrobenzoate, iso-5b, N-Me-iso-5b-O-3,5
      dinitrobenzoate, and 7b. As revealed by HPLC analysis, optical purity of the
      stereochemically labile alpha-aminoaldehydes is completely preserved under the
      conditions of hydrogen-mediated aldol coupling. Deletion of the intramolecular
      hydrogen bond, as in the case of N-methyl-N-Boc-l-leucinal N-Me-5a, inverts
      stereoselectivity to furnish the Felkin-Anh product N-Me-iso-5b in 17% yield.
      Additionally, reactions performed in the presence of tert-amyl alcohol (10 equiv)
      exhibit markedly lower levels of anti-Felkin-Anh control (7:1 versus > or =
      20:1). The collective studies suggest that intramolecular hydrogen bonding plays
      a key role in both activating the alpha-aminoaldehyde toward addition and
      directing facial selectivity.

PMID- 17177458
TI  - Total synthesis of (-)-heptemerone B and (-)-guanacastepene E.
AB  - A concise, stereoselective, and convergent total synthesis of the unnatural
      enantiomer of the neodolastane diterpenoid heptemerone B has been completed.
      Saponification of (-)-heptemerone afforded (-)-guanacastepene E. The absolute
      stereochemistry of (-)-heptemerone B was thus established as 5-(S), the same as (
      )-guanacastepene E. The longest linear sequence of the synthesis comprises 17
      (18) steps from simple known starting materials. Our general synthetic approach
      integrates a diverse set of reactions, including an intramolecular Heck reaction
      to create one quaternary stereocenter and a cuprate conjugate addition for the
      establishment of the other. The central seven-membered ring was closed with an
      uncommon electrochemical oxidation, whereas the five-membered ring was formed
      through ring-closing metathesis. The absolute configuration of the two key
      building blocks was established through an asymmetric reduction and an asymmetric
      ene reaction.

PMID- 17177460
TI  - Thermal formation of homochiral serine clusters and implications for the origin
      of homochirality.
AB  - Spontaneous assembly of amino acids into vapor-phase clusters occurs on heating
      the solid compounds in air. In comparison to the other amino acids, serine forms
      clusters to an unusual extent, showing a magic number octamer on sublimation;
      this octamer can be ionized and characterized by mass spectrometry. Two isomers
      of the vapor-phase serine octamer are generated, the minor one at 130 degrees C
      and the major at 220 degrees C. The higher temperature cluster shows a strong
      homochiral preference, as confirmed by isotopic labeling experiments. This serine
      cluster, like that generated earlier from solution in electrospray ionization
      experiments, undergoes gas-phase enantioselective substitution reactions with
      other amino acids. These reactions transfer the chirality of serine to the other
      amino acid through enantioselective incorporation into the octamer. Other serine
      pyrolysis products include alanine, glycine, ethanolamine, and small dipeptides,
      and many of these, too, are observed to be incorporated into the thermally formed
      serine octamers. Chiral chromatographic analysis confirmed that L-serine
      sublimation produced DL-alanine, glycine, and ethanolamine, while in the presence
      of hydrogen sulfide, L-serine yielded L-cysteine. The data demonstrate that
      sublimation of serine under relatively mild conditions yields chirally enriched
      serine octamers and that the chiral preference of the starting serine can be
      transferred to other compounds through cluster-forming chemical reactions.

PMID- 17177461
TI  - Cycloalkane and cycloalkene C-H bond dissociation energies.
AB  - Both C-H bond dissociation energies for cyclobutene were measured in the gas
      phase (BDE = 91.2 +/- 2.3 (allyl) and 112.5 +/- 2.5 (vinyl) kcal mol-1) via a
      thermodynamic cycle by carrying out proton affinity and electron-binding energy
      measurements on 1- and 3-cyclobutenyl anions. The results were compared to those
      for an acyclic model compound, cis-2-butene, and provide the needed information
      to experimentally establish the heat of formation of cyclobutadiene. Chemically
      accurate G3 and W1 calculations also were carried out on cycloalkanes,
      cycloalkenes, and selected reference compounds. It appears that commonly cited
      bond energies for cyclopropane, cyclobutane, and cyclohexane are 3 to 4 kcal mol
      1 too small and their pi bond strengths, as given by BDE1 - BDE2, are in error by
      up to 8 kcal mol-1.

PMID- 17177459
TI  - On the mechanism of an asymmetric alpha,beta-unsaturated carboxylic acid
      hydrogenation: application to the synthesis of a PGD2 receptor antagonist.
AB  - Ruthenium complexes employing axially chiral ligands were found to be effective
      asymmetric hydrogenation catalysts for the reduction of alpha,beta-unsaturated
      ene acid 1-E to give 2, a prostaglandin D2 (PGD2) receptor antagonist. With [(S
      BINAP)Ru(p-cymene)Cl2]2 (3, S-BINAP = (S)-(+)-2,2'-bis(diphenylphospino)-1,1'
      binapthyl), it was discovered that low hydrogen pressures (<30 psi) were
      essential to achieve high enantioselectivities (92% ee). A detailed mechanistic
      study was undertaken to elucidate this pressure dependence. It was determined
      that compound 1-E is in a ruthenium-catalyzed equilibrium with endocylic isomer 1
      Endo and in photochemical equilibrium with Z isomer 1-Z. Each isomer could be
      hydrogenated to give 2, albeit with different rates and enantioselectivities.
      Hydrogenation of 1-Endo with 3 was found to give 2 in high enantiomeric excess,
      regardless of pressure and at a rate substantially faster than that of
      hydrogenation of 1-E and 1-Z. In contrast, isomers 1-E and 1-Z exhibited pressure
      dependent enantioselectivities, with higher enantiomeric excesses obtained at
      lower pressures. A rationale for this pressure dependence is described. Deuterium
      labeling studies with 1-Endo and tiglic acid were used to elucidate the mechanism
      of hydride insertion and product release from ruthenium. Under neutral
      conditions, protonolysis was the major pathway for metal-carbon cleavage, while
      under basic conditions, hydrogenolysis of the metal-carbon bond was predominant.

PMID- 17177462
TI  - Chemistry of the silica surface: liquid-solid reactions of silica gel with
      trimethylaluminum.
AB  - The reaction of trimethylaluminum and dry, high-surface-area (500 m2/g) silica
      gel in a mixed slurry was studied using multinuclear, solid-state NMR
      spectroscopy. The products of the initial reaction were characterized, and their
      progress through subsequent washing with diethyl ether and reactions with
      measured amounts of water was followed. The quantitative distribution of
      different chemical forms of carbon deposited on the silica surface by the initial
      reaction was measured. The products of the initial reaction are dominated by
      methyl species of the types Al(CH3)n (with Si-O-Al linkages), Si-O-CH3, and (Si
      O)4-nSi(CH3)n; aluminum is seen to exist predominantly as a five-coordinate
      species. Subsequent treatment with diethyl ether fails to remove any surface
      species, but instead the ether becomes strongly associated with the surface and
      highly resistant to removal. Stepwise additions of water hydrolyze the Al-CH3 and
      Si-O-CH3 moieties, leading to conversion of five-coordinate aluminum to four- and
      six-coordinate aluminum, and affect the partial release of the surface-associated
      diethyl ether; Si-CH3 moieties remain. The effect of aromatic and saturated
      solvents on the initial reaction was examined and found to cause a small but
      significant change in the distribution of products. Structures of aluminum
      centered species on the silica surface consistent with the spectroscopic data are
      proposed.

PMID- 17177463
TI  - Population balance models and Monte Carlo simulation for nanoparticle formation
      in water-in-oil microemulsions: implications for CdS synthesis.
AB  - We address controlled CdS nanoparticle formation by tuning experimental synthesis
      conditions. To this end, a bivariate population balance equation (PBE) model has
      been developed based on time scale analysis, to explain the mechanism of
      nanoparticle formation in self-assembled templates. It addresses the process of
      mixing two water-in-oil (w/o) microemulsions, each containing a pre-dissolved
      reactant in the microemulsion drops. Brownian collision and coalescence of two
      water drops of nanometer size results in mixing and exchange of reactant
      molecules, leading to chemical reaction. The water insoluble reaction product
      nucleates to form a nanoparticle in an individual drop, which subsequently grows
      internally by consuming the excess product and by coalescence-exchange with other
      drops. Finite rates of nucleation and coalescence-exchange are accounted for in
      the PBE, while the rates of reaction and internal growth of nanoparticles are
      found to be instantaneous. Experimentally proven binomial redistribution of
      reactant and product molecules upon drop coalescence is implemented in the
      present work. This results in a very good prediction of experimental data of the
      mean aggregate number (MAN) and hence size of CdS nanoparticles. Both our model
      and Monte Carlo (MC) simulation quantitatively capture the reported variation of
      MAN with molar excess of Cd2+ concentration and microemulsion drop size. Our
      results together with previous experimental data establish that usage of
      stoichiometrically five times or more of excess Cd2+ concentration can cause
      surface adsorption and desirable enhanced emission intensity of CdS
      nanoparticles, without altering particle size. We also propose a simplified and
      computationally efficient univariate PBE model. The univariate model gives very
      fast (in minutes) and accurate estimates (for low reactant concentrations) of the
      number and mean size of CdS nanoparticles. Time-scale analysis offers a good a
      priori choice of the appropriate model based on range of reactant concentrations.

PMID- 17177464
TI  - Temperature- and solvent-dependent binding of dihydrogen in iridium pincer
      complexes.
AB  - Mixtures of deuterium labeled complexes (p-XPOCOP)IrH2-xDx (1-6-d0-2) {POCOP =
      [C6H2-1,3-[OP(tBu)2]2] X = MeO (1), Me (2), H (3), F (4), C6F5 (5), and ArF = 3,5
      (CF3)2-C6H3 (6)} have been generated by reaction of (p-XPOCOP)IrH2 complexes with
      HD gas in benzene followed by removal of the solvent under high vacuum.
      Spectroscopic analysis employing 1H and 2D NMR reveals significant temperature
      and solvent dependent isotopic shifts and HD coupling constants. Complexes 1-6-d1
      in toluene and pentane between 296 and 213 K exhibit coupling constants JHD of
      3.8-9.0 Hz, suggesting the presence of an elongated H2 ligand, which is confirmed
      by T1(min) measurements of complexes 1, 3, and 6 in toluene-d8. In contrast,
      complex 6-d1 exhibits JHD = 0 Hz in CH2Cl2 or CDCl2F whereas isotopic shifts up
      to -4.05 ppm have been observed by lowering the temperature from 233 to 133 K in
      CDCl2F. The large and temperature-dependent isotope effects are attributed to
      nonstatistical occupation of two different hydride environments. The experimental
      observations are interpreted in terms of a two component model involving rapid
      equilibration of solvated Ir(III) dihydride and Ir(I) dihydrogen structures.

PMID- 17177465
TI  - Metal-catalyzed phosphodiester cleavage: secondary 18O isotope effects as an
      indicator of mechanism.
AB  - Information about the transition states of metal-catalyzed hydrolysis reactions
      of model phosphate compounds has been obtained through determination of isotope
      effects (IEs) on the hydrolysis reactions. Metal complexation has been found to
      significantly alter the transition state of the reaction from the alkaline
      hydrolysis reaction, and the transition state is quite dependent on the
      particular metal ion used. For the diester, ethyl p-nitrophenyl phosphate, the
      nonbridge 18O effect for the hydrolysis reactions catalyzed by Co(III) 1,5,9
      triazacyclononane and Eu(III) were 1.0006 and 1.0016, respectively, indicative of
      a slightly associative transition state and little net change in bonding to the
      nonbridge oxygen. The reaction catalyzed by Zn(II) 1,4,7,10-tetraazacyclododecane
      had an 18O nonbridge IE of 1.0108, showing the reaction differs significantly
      from the reaction of the noncomplexed diester and resembles the reactions of
      triesters. Reaction with Co(III) 1,4,7,10-tetraazacyclododecane showed an inverse
      effect of 0.9948 reflecting the effects of bonding of the diester to the Co(III).
      Lanthanide-catalyzed hydrolysis has been observed to have unusually large 15N
      effects. To further investigate this effect, the 15N effect on the reaction
      catalyzed by Ce(IV) bis-Tris propane solutions at pH 8 was determined to be
      1.0012. The 15N effects were also measured for the reaction of the monoester p
      nitrophenyl phosphate by Ce(IV) bis-Tris propane (1.0014) and Eu(III) bis-Tris
      propane (1.0012). These smaller effects at pH 8 indicate that a smaller negative
      charge develops on the nitrogen during the hydrolysis reaction.

PMID- 17177466
TI  - Chiral self-recognition: direct spectroscopic detection of the homochiral and
      heterochiral dimers of propylene oxide in the gas phase.
AB  - In this report, we describe rotational spectroscopic and high-level ab initio
      studies of the 1:1 chiral molecular adduct of propylene oxide dimer. The
      complexes are bound by weak secondary hydrogen bonds, that is, the O(epoxy)...H-C
      noncovalent interactions. Six homochiral and six heterochiral conformers were
      predicted to be the most stable configurations where each monomer acts as a
      proton acceptor and a donor simultaneously, forming two six- or five-membered
      intermolecular hydrogen-bonded rings. Rotational spectra of six, that is, three
      homochiral and heterochiral conformer pairs, out of the eight conformers that
      were predicted to have sufficiently large permanent electric dipole moments were
      measured and analyzed. The relative conformational stability order and the signs
      of the chiral recognition energies of the six conformers were determined
      experimentally and were compared to the ab initio computational results. The
      experimental observations and the ab initio calculations suggest that the
      concerted effort of these weak secondary hydrogen bonds can successfully lock the
      subunits in a particular orientation and that the overall binding strength is
      comparable to a classic hydrogen bond.

PMID- 17177467
TI  - Mechanism of electrochemical charge transport in individual transition metal
      complexes.
AB  - We used electrochemical scanning tunneling microscopy (STM) and spectroscopy
      (STS) to elucidate the mechanism of electron transport through individual pyridyl
      based Os complexes. Our tunneling data obtained by two-dimensional
      electrochemical STS and STM imaging lead us to the conclusion that electron
      transport occurs by thermally activated hopping. The conductance enhancement
      around the redox potential of the complex, which is reminiscent of switching and
      transistor characterics in electronics, is reflected both in the STM imaging
      contrast and directly in the tunneling current. The latter shows a biphasic
      distance dependence, in line with a two-step electron hopping process. Under
      conditions where the substrate/molecule electron transfer (ET) step is dominant
      in determining the overall tunneling current, we determined the conductance of an
      individual Os complex to be 9 nS (Vbias = 0.1 V). We use theoretical approaches
      to connect the single-molecule conductance with electrochemical kinetics data
      obtained from monolayer experiments. While the latter leave some controversy
      regarding the degree of electronic coupling, our results suggest that electron
      transport occurs in the adiabatic limit of strong electronic coupling.
      Remarkably, and in contrast to established ET theory, the redox-mediated
      tunneling current remains strongly distance dependent due to the electronic
      coupling, even in the adiabatic limit. We exploit this feature and apply it to
      electrochemical single-molecule conductance data. In this way, we attempt to
      paint a unified picture of electrochemical charge transport at the single
      molecule and monolayer levels.

PMID- 17177469
TI  - Changeover during in situ compositional modulation of hexacyanoferrate (Prussian
      Blue) material.
AB  - This paper describes the importance of (H2O)6 clusters in controlling the
      properties of hexacyanoferrate (Prussian Blue) materials. A careful in situ study
      of compositional changes by using electrogravimetric techniques (in ac and dc
      modes) in hexacyanoferrates containing K+ alkali metals reveals the existence of
      a changeover in the properties of these films in a narrow potential range.
      Control of the compositional variation of the changeover is dependent on the K+
      stoichiometric number in the compound structure. However, a specific K+
      occupation in the compound structure activates the occupation of the (H2O)6
      cluster by H3O+ and/or H+, causing the changeover in the properties of
      hexacyanoferrate film. Thus, the information thus obtained is very useful for
      understanding the mechanisms involved in the electrochemical reversible switch
      between ferrimagnetism/paramagnetism, "semiconductor/metal" and
      electroluminescence/nonelectroluminescence properties of molecular cyanide
      materials.

PMID- 17177468
TI  - When does an intermediate become a transition state? Degenerate isomerization
      without competing racemization during solvolysis of (S)-1-(3-nitrophenyl)ethyl
      tosylate.
AB  - (S)-1-(3-Nitrophenyl)ethyl tosylate [(S)-2-OTs] was prepared in >99% enantiomeric
      excess and the change in the chiral purity of this compound was monitored during
      solvolysis in 50:50 trifluoroethanol/water. The barely detectable formation of
      0.5% (R)-2-OTs after two half times for the solvolysis reaction was used to
      calculate a rate constant of k(rac) approximately equal to 4 x 10-6 s-1. This is
      80-fold smaller than kiso = 3.2 x 10-4 s-1 for the isomerization that exchanges
      oxygen-16 and oxygen-18 of 3-NO2C6H413CH(Me)OS(18O)2Tos during solvolysis and 10
      fold smaller than the minimum value of k(rac) = 4.6 x 10-5 s-1 predicted if
      isomerization and racemization products form by partitioning of a common ion-pair
      intermediate of a stepwise reaction. It is concluded that the isomerization
      reaction proceeds mainly by a pathway that avoids formation of this putative
      intermediate. It is suggested that the solvolysis reaction of 2-OTs may proceed
      by a stepwise preassociation mechanism where solvent "reorganization" precedes
      substrate ionization to form an ion-pair intermediate.

PMID- 17177480
TI  - Mycotoxins in pet food: a review on worldwide prevalence and preventative
      strategies.
AB  - Mycotoxins contaminate cereal grains worldwide, and their presence in pet food
      has been a potential health threat to companion animals. Aflatoxins, ochratoxin
      A, and Fusarium mycotoxins have been found in both raw ingredients and final
      products of pet food around the globe. Aflatoxin, a hepatotoxin and carcinogen,
      has caused several food poisoning outbreaks in dogs, and aflatoxin content is
      regulated in pet food in many countries. Ochratoxin A and Fusarium mycotoxins
      including trichothecenes, zearalenone, and fumonisins may have chronic effects on
      the health of companion animals. Grain processing, sampling error, analytical
      methods, conjugated mycotoxins, storage conditions, and synergistic interactions
      are common challenges faced by the pet food industry. Food-processing techniques
      such as sieving, washing, pearling, ozonation, and acid-based mold inhibition
      reduce the mycotoxin content of cereal grains. Dietary supplementation with large
      neutral amino acids, antioxidants, and omega-3 polysaturated fatty acids as well
      as inclusion of mycotoxin-sequestering agents and detoxifying microbes may
      ameliorate the harmful effects of mycotoxins in contaminated pet food.

PMID- 17177481
TI  - Using trifluoroacetic acid to augment studies of potato suberin molecular
      structure.
AB  - Systematically varied reaction times and concentrations of trifluoroacetic acid
      (TFA) have been used to remove polysaccharides associated with suberin isolated
      from potato wound periderm, thereby augmenting spectroscopic determinations of
      the molecular structure of this protective plant polyester. Treatments with
      dilute TFA left a residual insoluble material for which both solid-state 13C and
      1H NMR spectra displayed significant improvements in resolution without
      compromising the integrity of the protective plant polyester, whereas higher
      concentrations of TFA made it possible to achieve controlled hydrolysis of the
      suberin aliphatic or aromatic domains. Among the isolated fragments were two
      hydroxyphenyl derivatives reported previously in lignins and a novel aliphatic
      aromatic ester trimer that is identified provisionally. Together these protocols
      help to characterize the carbohydrate types that are bound covalently to the
      suberin polyester and to identify the interunit covalent linkages among the
      aliphatic ester, phenolic, and carbohydrate moieties in suberized potato tissue.
      The strategies described herein may also advance molecular-level investigations
      of lignocellulosic materials or vegetable tissues that exhibit strengthened
      intercellular adhesion.

PMID- 17177482
TI  - Multiresidue method for determination of 35 pesticides in virgin olive oil by
      using liquid-liquid extraction techniques coupled with solid-phase extraction
      clean up and gas chromatography with nitrogen phosphorus detection and electron
      capture detection.
AB  - A method for the multiresidue determination of 35 pesticides (30 insecticides and
      five herbicides) in olive oil by gas chromatography (GC) is described. Three
      liquid-liquid extraction (LLE) procedures based on (i) partition of pesticides
      between acetonitrile (ACN) and oil solution in n-hexane, (ii) partition of
      pesticides between saturated ACN with n-hexane and oil solution in n-hexane
      saturated with ACN, and (iii) partition of pesticides between ACN and oil were
      tested for the optimization of the highest pesticide recoveries with the lowest
      oil residue in the final extracts. Experimental tests were preformed in order to
      study the efficiency of different clean up procedures with N-Alumina, Florisil,
      C18, and ENVI-Carb solid-phase extraction (SPE) cartridges for the compounds
      analyzed by GC-nitrogen phosphorus detection. A second step of clean up was also
      performed for the compounds analyzed by GC-electron capture detection (ECD), by
      using phenyl-bonded silica (Ph), diol-bonded silica (Diol), cyanopropyl-bonded
      silica (CN), and amino propyl-bonded silica (NH2) SPE cartridges. LLE of the oil
      solution in hexane with ACN followed by an ENVI-Carb SPE clean up of the extract
      gave the best results for all target compounds. The ACN extract was additionally
      cleaned through a Diol-SPE cartridge for the determination of pesticides analyzed
      mainly by GC-ECD. Pesticide recoveries form virgin olive oil spiked with 20, 100,
      and 500 microg/kg concentrations of pesticides ranged from 70.9 to 107.4%. The
      proposed method featured good sensitivity, pesticide quantification limits were
      low enough, and the precision, expressed as relative standard deviation, ranged
      from 2.4 to 12.0%. The proposed method was applied successfully for the residue
      determination of the selected pesticides in commercial olive oil samples.

PMID- 17177483
TI  - Rapid determination of the main organic acid composition of raw Japanese apricot
      fruit juices using near-infrared spectroscopy.
AB  - The potential of near-infrared (NIR) spectroscopy to rapidly determine citric and
      malic acid contents of raw Japanese apricot (Japanese "ume", also known as the
      Japanese plum) fruit juice was investigated. In total, 314 raw juice samples with
      different organic acid compositions were collected over a long growth period, and
      spectra (1100-1850 nm) of these samples were acquired using an NIR
      spectrophotometer with a 1-mm path length. Calibrations were performed using a
      partial least-squares regression method based on a calibration sample set (211
      samples), while validations were performed based on a validation sample set (103
      samples). The results revealed good agreement between NIR spectroscopy and
      capillary electrophoresis, including the correlation coefficient (r2), standard
      error of prediction (SEP), and bias; no statistically (p = 0.05) significant
      differences were found for these parameters. Moreover, standard deviation ratios
      of reference data in the validation sample set to the SEP were higher than 3,
      indicating that NIR spectroscopy may represent an acceptable method for
      quantitative evaluation of citric and malic acids in raw Japanese apricot fruit
      juice.

PMID- 17177484
TI  - Equal performance of TaqMan, MGB, molecular beacon, and SYBR green-based
      detection assays in detection and quantification of roundup ready soybean.
AB  - We have tested and compared the performance of 12 different assays representing
      four different real-time polymerase chain reaction (PCR) chemistries in the
      context of genetically modified organism detection. Several different molecular
      beacon, SYBR Green, TaqMan, and MGB assays were designed for the event specific
      detection and quantification of the 3' integration junction of GTS 40-3-2
      (Roundup Ready) soybean. Sensitivity as well as robustness in the presence of
      background DNA were tested. None of the PCR-based approaches appeared to be
      significantly better than any of the other, but the molecular beacon assays had
      the lowest efficiency and also seemed more sensitive to changes in experimental
      setup.

PMID- 17177485
TI  - Alkaline dissolution of starch facilitated by microwave heating for analysis by
      size-exclusion chromatography.
AB  - A rapid, straightforward starch dissolution method was developed to facilitate
      analysis of starch by size-exclusion chromatrography (SEC). Soft wheat starch was
      dispersed in 6 M urea and 1 M KOH and subjected to heating for 35, 45, or 60 s in
      a microwave oven as a potential means of starch dissolution. An increase in
      microwave heating time enhanced starch solubility but resulted in a steady
      decrease in amylopectin peak area and a consequent, artifactual increase in the
      amylose peak area due to molecular degradation. However, microwave heating for 35
      s afforded a reasonable separation of starch fractions by SEC while minimizing
      molecular degradation of starch in comparison to a traditional starch dissolution
      procedure. This procedure provides a fast (<30 min), simple, and reproducible
      starch dissolution method for preparation of starches for SEC analysis and
      represents the first successful report of direct dissolution of granular starch
      via microwave heating.

PMID- 17177486
TI  - Determination of fluoroquinolones in milk samples by postcolumn derivatization
      liquid chromatography with luminescence detection.
AB  - A liquid chromatography (LC) method with luminescence detection for the
      determination of eight quinolone antibiotics is reported. The system encompasses
      three consecutive steps: (a) chromatographic separation using reverse-phase mode
      (RP-LC), (b) postcolumn derivatization reaction, and (c) luminescence detection
      by monitoring fluorescence (FL) and time-resolved (TR) signals. The
      derivatization step is based on the reaction between quinolones and terbium(III)
      to form luminescent chelates, which were determined at lambda(ex) 340 and
      lambda(em) 545 nm (FL mode) or at lambda(ex) 281 and lambda(em) 545 nm (TR mode).
      Dynamic ranges of the calibration graphs, obtained with standard solutions of
      analytes and FL and TR modes, respectively, were 190-3500 and 316-2000 ng mL-1
      for marbofloxacin, 8-3500 and 8.1-1500 ng mL-1 for ciprofloxacin, 6.2-3500 and 13
      1500 ng mL-1 for danofloxacin, 7.4-3500 and 8.4-1500 ng mL-1 for enrofloxacin, 14
      3500 and 20-2000 ng mL-1 for sarafloxacin, 12.5-3500 and 13.9-1200 ng mL-1 for
      difloxacin, 7.6-3500 and 13-3000 ng mL-1 for oxolinic acid, and 9-2000 and 130
      3000 ng mL-1 for flumequine. Limit of detection values obtained using FL and TR
      modes, respectively, were 60 and 95 ng mL-1 for marbofloxacin, 2 and 2.4 ng mL-1
      for ciprofloxacin, 1.9 and 3.9 ng mL-1 for danofloxacin, 2.2 and 2.5 ng mL-1 for
      enrofloxacin, 3.8 and 7 ng mL-1 for sarafloxacin, 4 and 4.2 ng mL-1 for
      difloxacin, 2.3 and 4 ng mL-1 for oxolinic acid, and 2.7 and 40 ng mL-1 for
      flumequine. The precision was established at two concentration levels of each
      analyte and expressed as the percentage of relative standard deviation with
      values ranging between 1.9 and 7.8%. The validation procedure for the analysis of
      samples was carried out using European Community recommendations, and the
      decision limit and detection capability were calculated for bovine whole milk.
      The method was applied to whole, semiskimmed, and skimmed milk samples spiked
      with the target analytes, and the recoveries ranged between 93.3 and 106.0%.

PMID- 17177487
TI  - Differences between lignin in unprocessed wood, milled wood, mutant wood, and
      extracted lignin detected by 13C solid-state NMR.
AB  - Solid-state 13C nuclear magnetic resonance (NMR) spectroscopy was applied to
      intact and isolated loblolly pine wood samples to identify potential structural
      changes induced by tree age, milling, lignin extraction, or naturally occurring
      mutations. Special attention was paid to ketone and aldehyde as well as nonpolar
      alkyl groups, which could be observed at low concentrations (<2 in 1000 C) using
      improved spinning-sideband suppression with gated decoupling. Carbonyl structures
      were present in intact wood, and there are more keto groups than aldehydes. Their
      concentrations increased from juvenile to mature wood and with milling time,
      whereas extraction did not alter the C=O fraction. Significant amounts of
      aldehyde and dihydroconiferyl alcohol residues were present in coniferyl aldehyde
      dehydrogenase-deficient wood, confirming solution-state NMR spectra of the
      corresponding lignin. These results demonstrate the utility of solid-state NMR as
      an assay for changes in the lignin structure of genetically modified plants.

PMID- 17177488
TI  - Screening of tetracycline residues in fish muscles by CCD camera-based solid
      surface fluorescence.
AB  - A methodology for the screening of tetracyclines (TCs), including tetracycline
      (TC), oxytetracycline (OTC), and chlorotetracycline (CTC), in different fish
      muscle matrices has been proposed. This method was based on in situ fluorescent
      derivation of TCs, transferring weakly fluorescing TCs to highly fluorescent
      species, on alkaline-activated solid silica gel G plates (SGGPs). By coupling
      solid-surface fluorescence (SSF) with charge-coupled device (CCD) camera imaging,
      a CCD camera-based SSF (CCD-SSF) methodology has been developed. Calibration
      curve, repeatability, selectivity, limit of detection (LOD), and limit of
      quantification (LOQ) have been explored for evaluating the performance of the
      method itself. Linear calibration curves were obtained over a range of 0.20-1.0
      ng/spot for all three TCs. The LODs, defined as 3sigma, for TC, OTC, and CTC were
      0.14, 0.15, and 0.16 ng/spot, respectively. The trueness of method was validated
      by HPLC, and no significant difference between CCD-SSF and HPLC was found, on a
      basis of 95% confidence level. By spiked recovery studies, a linear calibration
      curve ranging from 20 to 300 microg/kg of TC in fish muscle samples with a
      correlation coefficient (R 2) equal to 0.994 was obtained. The total average
      recovery for TC in fish muscle samples from six different fish matrices,
      fortified with TC at 50, 100, and 200 microg/kg levels, was 75.7% with average
      relative standard deviations (RSDs) ranging from 2.0 to 7.7%. RSDs ranged from
      2.5 to 5.8% and from 5.2 to 7.6% for in-day and interday repeatability,
      respectively. The detection and quantification limits in fish muscle matrices
      were 16 and 53 microg/kg of TCs, respectively. The newly developed CCD-SSF method
      has been applied to the screening of the TC residues in fish muscle samples. The
      method has been demonstrated to bear some advantages, such as its simplicity,
      high throughput, low cost, use of fewer pollutants, and reasonable sensitivity.

PMID- 17177489
TI  - Comparative evaluation of three lignin isolation protocols for various wood
      species.
AB  - Milled wood lignin (MWL), cellulolytic enzyme lignin (CEL), and enzymatic mild
      acidolysis lignin (EMAL) were isolated from different wood species and
      characterized by various techniques. The EMAL protocol offered gravimetric lignin
      yields 2-5 times greater than those of the corresponding MWL and CEL. The
      purities of the EMALs were 3.75-10.6% higher than those of their corresponding
      CELs, depending upon the wood species from which they were isolated. Molecular
      weight analyses showed that the EMAL protocol isolates lignin fractions that are
      not accessed by the other procedures evaluated, while 31P NMR spectroscopy
      revealed that MWL is more condensed and bears more phenolic hydroxyl groups than
      EMAL and CEL. The yields and purities of EMAL, MWL, and CEL from hardwood were
      greater than those obtained for the examined softwoods. Structural details
      obtained by DFRC (derivatization followed by reductive cleavage)/31P NMR revealed
      different contents of condensed and uncondensed beta-O-aryl ether structures,
      dibenzodioxocins, and condensed and uncondensed phenolic hydroxyl and carboxylic
      acid groups within lignins isolated from different wood species.

PMID- 17177490
TI  - Discrimination and classification of olive tree varieties and cultivation zones
      by biophenol contents.
AB  - The peak areas from a high-performance liquid chromatography-diode array (HPLC
      DAD) analysis of biophenols extracted from olive leaves have been used as
      chemotaxonomic markers to construct chemometric models in order to discriminate
      and classify (1) 13 varieties of Olea europaea olive trees, namely, Alameno,
      Arbequina, Azulillo, Chorna, Hojiblanca, Lechin, Manzanillo, Negrillo, Nevadillo,
      Ocal, Pierra, Sevillano, and Tempranillo, from the same cultivation zone and (2)
      Arbequina samples from six different geoghaphical origins, namely, Cordoba,
      Mallorca (north and south), Ciudad Real, Lleida, and Navarra. Models based on
      principal component analysis (PCA) and hierarchical cluster analysis (HCA) were
      used for discrimination between samples as a function of the tree varieties and
      cultivation zone, whereas K nearest neighbors (KNN) and soft independent modeling
      of class analogy (SIMCA) models were generated to classify the samples used to
      validate the models into one of the groups previously established by PCA and HCA.
      KNN classified correctly 93 and 92% of the samples into the variety and
      cultivation zone, respectively; meanwhile, the SIMCA models predicted 85 and 92%,
      respectively.

PMID- 17177491
TI  - Development of a rapid "fingerprinting" system for wine authenticity by mid
      infrared spectroscopy.
AB  - This paper reports on the development of a rapid and simple method for red wine
      authenticity confirmation during transport and processing; namely, a wine
      "fingerprinting" system. When wine is transported between two sites, a sample is
      taken and a mid-infrared (MIR) spectrum is obtained. One hundred sixty-one (n =
      161) samples of three main red wine varieties grown in Australia, Shiraz,
      Cabernet Sauvignon, and Merlot, were collected from six commercial wineries
      across Australia and scanned in transmission on two MIR spectrophotometers
      located at The Hardy Wine Company's main site at Reynella, South Australia (Foss
      WineScan FT 120) (926-5012 cm-1). A similarity index (SI) method was used as a
      tool to classify wine samples on the basis of their spectral data. The results
      showed that high rates of classification were obtained when wine samples scanned
      in different instruments were analyzed. The SI has been proven to provide an
      acceptable measurement for authentication of red wine integrity during
      transportation. In five of the six winery data sets, the SI correctly classified
      98% of the wines. It was also observed that less than 1% of wines were
      misclassified between the different wineries investigated. Further studies are
      needed in order to test the applicability of the SI in a commercial situation and
      to evaluate its potential as a rapid quality control tool for routine use to
      authenticate wine samples during transport.

PMID- 17177492
TI  - Liquid chromatography coupled to isotope ratio mass spectrometry: a new
      perspective on honey adulteration detection.
AB  - A new procedure to determine individual sugar (sucrose, glucose, and fructose)
      13C isotope ratios, using liquid chromatography-isotope ratio mass spectrometry
      (HPLC-IRMS), has been developed to improve isotopic methods devoted to the study
      of honey authenticity. For this purpose 79 commercial honey samples from various
      origins were analyzed. Values of delta13Choney ranged from -14.2 to -27.2", and
      delta13Cprotein ranged from -23.6 to -26.9". A very strong correlation is
      observed between the individual sugar 13C ratios, which are altered in the event
      of sugar addition, even at low levels. The use of Deltadelta13C [fruct-glu],
      Deltadelta13C [fruct-suc], and Deltadelta13C [gluc-suc] systematic differences as
      an authenticity criterion permits the sugar addition [C3, beet sugar; or C4, cane
      sugar, cane syrup, isoglucose syrup, and high-fructose corn syrup (HFCS)] to be
      reliably detected (DL = 1-10%). The new procedure has advantages over existing
      methods in terms of analysis time and sensitivity. In addition, it is the first
      isotopic method developed that allows beet sugar addition detection.

PMID- 17177493
TI  - Immunochromatography using colloidal gold-antibody probe for the detection of
      atrazine in water samples.
AB  - An immunochromatography (ICG) strip test for rapid detection of atrazine in water
      samples was developed. A monoclonal antibody (MAb) specific to atrazine was
      produced from the cloned hybridoma cell (AT-1-M3) and used to develop a direct
      competitive enzyme-linked immunosorbent assay (DC-ELISA) and ICG strip. MAb
      conjugated to colloidal gold, and that was applied to the conjugate pad of the
      ICG strip. The visual detection limit for the ICG strip was 3 ng/mL. This test
      required only 10 min to get results and one step of sample to perform the assay.
      The results of water samples spiked with 5, 10, 20, and 50 ng/mL of atrazine by
      ICG strip were in good agreement with those obtained by DC-ELISA. The ICG strip
      was sufficiently sensitive and accurate to be useful for rapid screening of
      atrazine in various water samples.

PMID- 17177494
TI  - Event-specific qualitative and quantitative polymerase chain reaction analysis
      for genetically modified canola T45.
AB  - Polymerase chain reaction (PCR) methods have been the main technical support for
      the detection of genetically modified organisms (GMOs). To date, GMO-specific PCR
      detection strategies have been developed basically at four different levels, such
      as screening-, gene-, construct-, and event-specific detection methods. Event
      specific PCR detection method is the primary trend in GMO detection because of
      its high specificity based on the flanking sequence of exogenous integrant. GM
      canola, event T45, with tolerance to glufosinate ammonium is one of the
      commercial genetically modified (GM) canola events approved in China. In this
      study, the 5'-integration junction sequence between host plant DNA and the
      integrated gene construct of T45 canola was cloned and revealed by means of TAIL
      PCR. Specific PCR primers and TaqMan probes were designed based upon the revealed
      sequence, and qualitative and quantitative TaqMan real-time PCR detection assays
      employing these primers and probe were developed. In qualitative PCR, the limit
      of detection (LOD) was 0.1% for T45 canola in 100 ng of genomic DNA. The
      quantitative PCR assay showed limits of detection and quantification (LOD and
      LOQ) of 5 and 50 haploid genome copies, respectively. In addition, three mixed
      canola samples with known GM contents were detected employing the developed real
      time PCR assay, and expected results were obtained. These results indicated that
      the developed event-specific PCR methods can be used for identification and
      quantification of T45 canola and its derivates.

PMID- 17177495
TI  - Determination of traces of fipronil and its metabolites in pollen by liquid
      chromatography with electrospray ionization-tandem mass spectrometry.
AB  - Fipronil is a pesticide suspected of having harmful effects on honey bees at
      microgram per kilogram levels. Considering the lack of methodology, it thus
      appeared to be necessary to develop a method for the determination of the lowest
      amounts of fipronil and its metabolites in pollen. This paper describes a new
      analytical method with a limit of quantification (LOQ) of 0.1 microg/kg for a
      representative sample weight of 5 g. In the case of a field study, this tool was
      used for checking the possible existence of fipronil and/or metabolites in pollen
      samples, but none of them contained residues higher than the LOQ. This three-step
      rapid method uses liquid-solid solvent extraction with mechanical grinding,
      followed by liquid-liquid partitioning and Florisil solid-phase extraction for
      the two cleanup steps. The quantification is made by liquid chromatography with
      electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Indeed, combined
      with an adequate sample treatment, this technique offers good sensitivity and
      selectivity in such a complex matrix. The method has given good recoveries of 74
      104% with relative standard deviations of 5.6-18.2%.

PMID- 17177496
TI  - Ovipositional responses of the pulse beetle, Bruchus chinensis (Coleoptera:
      Bruchidae) to extracts and compounds of Capparis decidua.
AB  - Extracts of Capparis decidua stems and flowers showed insecticidal and
      oviposition inhibitory activities against Bruchus chinensis. The LC50 values of
      these extracts were found to increase with the increase in the polarity of the
      extract at different exposure periods. For instance, after 96 h, the LC50 values
      were found to be 3.619, 7.319, and 10.151 microg for CD1, CD2, and CD3,
      respectively. Extract CD7 was effective only at higher doses. The toxicity was
      found to be dose- and time-dependent. The females laid lesser number of eggs,
      when exposed to sublethal doses of different extracts and pure compounds, as
      compared to control. The maximum oviposition deterrence index was found for
      extract CD1 followed in decreasing order by CD2, CD3, and CD7. From extract CD1,
      two compounds were isolated and characterized as triacontanol (C1) and 2-carboxy
      1,1-dimethylpyrrolidine (C2). When the females were exposed to sublethal doses of
      these compounds, they laid lesser number of eggs as compared to the control. C2
      was found to have a slightly greater oviposition inhibition effect than C1. From
      fraction CD7, one novel compound labeled as CDF1 has been isolated and identified
      as 6-(1-hydroxy-non-3-enyl)tetrahydropyran-2-one. CDF1 has also shown
      insecticidal and oviposition inhibitory activities against B. chinensis at low
      concentrations.

PMID- 17177497
TI  - Critical assessment of various techniques for the extraction of carotenoids and
      co-enzyme Q10 from the Thraustochytrid strain ONC-T18.
AB  - A variety of techniques for extracting carotenoids from the marine
      Thraustochytrium sp. ONC-T18 was compared. Specifically, the organic solvents
      acetone, ethyl acetate, and petroleum ether were tested, along with direct and
      indirect ultrasonic assisted extraction (probe vs bath) methods. Techniques that
      used petroleum ether/acetone/water (15:75:10, v/v/v) with 3 h of agitation, or 5
      min in an ultrasonic bath, produced the highest extraction yields of total
      carotenoids (29-30.5 microg g-1). Concentrations up to 11.5 microg g-1 of
      canthaxanthin and 17.5 microg g-1 of beta;-carotene were detected in extracts
      stored for 6 weeks. Astaxanthin and echinenone were also detected as minor
      compounds. Extracts with and without antioxidants showed similar carotenoid
      concentration profiles. However, total carotenoid concentrations were
      approximately 8% higher when antioxidants were used. Finally, an easy-to-perform
      and inexpensive method to detect co-enzymes in ONC-T18 was also developed using
      silica gel TLC plates. Five percent methanol in toluene as a mobile phase
      consistently eluted co-enzyme Q10 standards and could separate the co-enzyme
      fractions present in ONC-T18.

PMID- 17177498
TI  - Inhibition of diacylglycerol acyltransferase by alkamides isolated from the
      fruits of Piper longum and Piper nigrum.
AB  - Pharmacological inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT, EC
      2.3.1.20) has emerged as a potential therapy for the treatment of obesity and
      type 2 diabetes. Bioassay-guided isolation of CHCl3 extracts of the fruits of
      Piper longum and Piper nigum (Piperaceae), using an in vitro DGAT inhibitory
      assay, lead to isolation of a new alkamide named (2E,4Z,8E)-N-[9-(3,4
      methylenedioxyphenyl)-2,4,8-nonatrienoyl]piperidine (2), together with four known
      alkamides: retrofractamide C (1), pipernonaline (3), piperrolein B (4), and
      dehydropipernonaline (5). Compounds 2-5 inhibited DGAT with IC50 values of 29.8
      (2), 37.2 (3), 20.1 (4), and 21.2 (5) microM, respectively, but the IC50 value
      for 1 was more than 900 microM. This finding indicates that compounds possessing
      piperidine groups (2-5) can be potential DGAT inhibitors.

PMID- 17177499
TI  - Antioxidant activity of indigenous edible mushrooms.
AB  - The current study was undertaken to measure the antioxidant potential from water
      and methanolic extracts of fruiting bodies of 23 species of mushrooms naturally
      grown in different geographic locations of India. The antioxidant ability of each
      species was analyzed for the total antioxidative status, employing
      multimechanistic antioxidative assays such as inhibition of lipid peroxidation,
      determination of reducing power, and free radical scavenging ability, in addition
      to determination of total phenolics and identification of phenolic acids by HPLC
      analysis, because the phenolics are known to contribute largely to antioxidant
      potential. The antioxidant potential of these varieties of mushrooms was
      determined by summing the antioxidative activity (AOA) of each variety by varied
      antioxidant assays followed by determining the relative percent of AOA defined as
      the "antioxidant index" (AI). On the basis of the AI, the mushroom species were
      graded as very high, high, moderate, and low. Termitomyces heimii was identified
      as the best variety, which showed 100% AI with 37 mg of phenolics/g of sample,
      418 units of reducing power ability (RPA)/g, and an IC50 of approximately 1.1 mg
      (dry weight)/mL, free radical scavenging activity (FRS) in the water extract
      followed by 11.2 mg of phenolics/g, 275 units of RPA/g, and an IC50 of
      approximately 2.7 mg (dry weight)/mL of FRS in the methanolic extract. Following
      T. heimii, Termitomyces mummiformis exhibited an AI of 86% within the "very high"
      group. Potent inhibitions of lipid peroxidation of approximately 100 and 69% was
      also observed in T. heimii and T. mummiformis, respectively. Water extracts
      ranged from 34 to 49% and methanolic extracts varied from 20 to 32% on dry weight
      of mushroom fruiting body. Total phenolic compounds were higher in the water
      extracts (2-37 mg/g) than in methanolic extract (0.7-11.2 mg/g). The AOA measured
      in the water extract was better than that from the methanolic extract. HPLC
      analysis of phenolic acids in the two mushroom species, namely, T. heimii and T.
      mummiformis, displaying maximum AOA potential indicated a preponderance of tannic
      acid, gallic acid, protocatacheuic acid, and gentisic acid. Studies thus provide
      the precise antioxidant status of 23 indigenous species of mushrooms, which can
      serve as a useful database for the selection of mushrooms for the function of
      preparation of mushroom-based nutraceutics.

PMID- 17177500
TI  - Antioxidant and choleretic properties of Raphanus sativus L. sprout (Kaiware
      Daikon) extract.
AB  - Brassica vegetables and glucosinolates contained therein are supposed to reduce
      the risk of cancer and to possess health-promoting properties. The benefits of a
      Brassica-based diet may be particularly expressed by eating sprouts, in which the
      glucosinolate content is higher than in mature vegetables. With this in mind, a
      first objective of this study was to evaluate the antioxidant properties of
      radish (Raphanus sativus L.) sprouts (Kaiware Daikon) extract (KDE), in which the
      glucosinolate glucoraphasatin (GRH), showing some antioxidant activity, is
      present at 10.5% w/w. The contribution of GRH to KDE's antioxidant activity was
      considered in two chemical assays (Trolox equivalent antioxidant capacity and
      Briggs-Rauscher methods). The total phenol assay by Folin-Ciocalteu reagent was
      performed to quantify the reducing capacity of KDE. Finally, on the basis of the
      putative choleretic properties of antioxidant plant extracts, the effect on the
      bile flow of KDE administration was investigated in an animal experimental model.
      The findings showed that KDE has antioxidant properties and significantly induced
      bile flow in rats administered 1.5 g/kg of body weight for 4 consecutive days.

PMID- 17177501
TI  - Influence of glycosidic linkages and molecular weight on the fermentation of
      maltose-based oligosaccharides by human gut bacteria.
AB  - A structure-function study was carried out to increase knowledge of how
      glycosidic linkages and molecular weights of carbohydrates contribute toward the
      selectivity of fermentation by gut bacteria. Oligosaccharides with maltose as the
      common carbohydrate source were used. Potentially prebiotic alternansucrase and
      dextransucrase maltose acceptor products were synthesized and separated into
      different molecular weights using a Bio-gel P2 column. These fractions were
      characterized by matrix-assisted laser desorption/ionization time-of-flight.
      Nonprebiotic maltooligosaccharides with degrees of polymerization (DP) from three
      to seven were commercially obtained for comparison. Growth selectivity of fecal
      bacteria on these oligosaccharides was studied using an anaerobic in vitro
      fermentation method. In general, carbohydrates of DP3 showed the highest
      selectivity towards bifidobacteria; however, oligosaccharides with a higher
      molecular weight (DP6-DP7) also resulted in a selective fermentation.
      Oligosaccharides with DPs above seven did not promote the growth of "beneficial"
      bacteria. The knowledge of how specific structures modify the gut microflora
      could help to find new prebiotic oligosaccharides.

PMID- 17177502
TI  - Naturally occurring estrogens in processed milk and in raw milk (from gestated
      cows).
AB  - The occurrence of the steroid hormones estrone (E1), 17alpha-estradiol (alphaE2),
      17beta-estradiol (betaE2), and estriol (E3) in processed bovine milk with
      different fat contents and in raw milk from (non)gestated cows was investigated.
      Following liquid extraction, optional enzymatical deconjugation, C18 solid-phase
      extraction, and derivatization, estrogens were analyzed using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Free and deconjugated E1 (6.2
      1266 ng/L) was the major estrogen followed by alphaE2 (7.2-322 ng/L) and betaE2
      (5.6-51 ng/L), whereas E3 was detected regularly at the detection limit of 10
      ng/L. The lowest and highest concentrations were determined in raw milk from
      nonpregnant and from cows in the third trimester of gestation, respectively. The
      estrogen concentration in processed milk coincides with that of raw milk between
      first and second trimesters, reflecting the contribution of lactating pregnant
      cows to the final consumable product. The daily intake of total investigated
      estrogens through milk is 372 ng, which is dramatically more than currently
      recognized.

PMID- 17177503
TI  - Wheat bran oil and its fractions inhibit human colon cancer cell growth and
      intestinal tumorigenesis in Apc(min/+) mice.
AB  - This study was designed to investigate the cancer preventive activities of wheat
      bran (WB) oil. We studied the colon cancer preventive effects of WB oil and its
      subfractions in the Apc(min/+) mouse model, a recognized mouse model for human
      colorectal cancer, and used human colon cancer cell lines (HCT-116 and HT-29) to
      identify possible active fractions in WB oil. Our results showed that the oil
      fraction of WB was more active than the water fraction against the growth of
      human colon cancer cell lines and that 2% WB oil significantly inhibited the
      overall tumorigenesis by 35.7% (p < 0.0001) in the Apc(min/+) mouse model. The WB
      oil was further fractioned into nonpolar lipids and phytochemicals and the
      phytochemical fraction was fractionated into phytosterols and phytosterol
      ferulates, 5-alk(en)ylresorcinols, and unidentified constituents by normal phase
      silica gel column chromatography. Results on cell culture showed that the
      phytochemical fraction had a higher inhibitory effect on HCT-116 human colon
      cancer cells than that of WB oil, whereas the nonpolar lipid fraction had less
      growth inhibitory effectiveness. However, neither fractions showed a stronger
      inhibition than WB oil in the Apc(min/+) mouse model. The current results
      demonstrate, for the first time, the intestinal cancer preventive activity of WB
      oil. The active ingredients, however, remain to be identified.

PMID- 17177504
TI  - Distinctive antioxidant and antiinflammatory effects of flavonols.
AB  - The antioxidant and antiinflammatory effects of flavonols have been suggested to
      be structure-related. Results revealed that selected flavonols, including fisetin
      (F), kaempferol (K), morin (MO), myricetin (MY), and quercetin (Q), exhibited
      distinctive free radical scavenging properties against different kinds of free
      radicals. The H donation (DPPH bleaching) potential was Q > F approximately
      equals MY > MO > K, indicating that the presence of a 3',4'-catechol moiety in
      the B ring correlated with high activity. The 4'-OH in the B ring was suggested
      to be important for reducing xanthing/xanthine oxidase-generated superoxide;
      while an additional OH moiety on the ortho sites (3' or 5') attenuated the effect
      as the observed inhibitory potency was K approximately equals MO > Q > F > MY.
      The relative inhibitory effect for Fenton-mediated hydroxyl radical was K
      approximately equals MO approximately equals Q > F > MY. This result implies the
      involvement of 4-keto, 5-OH region in Fe++ chelating and the negative effect of
      pyrogallol moiety in the B ring. Similar to the inhibitory activity against a N
      formyl-methionyl-leucyl-phenylalanine (f-MLP)-stimulated oxidative burst in human
      polymorphonuclear neutrophils (PMN), our result showed that the structural
      peculiarity of the di-OH in the B ring obviously rendered F, Q, and MO more
      potent as ROS inhibitors than MY and K, which have tri- and mono-OH in the B
      ring, respectively. All of the previous data indicated that the structure
      prerequisite to reinforce the free radical scavenging activity varies with the
      type of free radical. We further analyzed the effects of flavonols on nitric
      oxide (NO) production in endotoxin-stimulated murine macrophages, RAW264.7 cells.
      Results showed that all flavonols (up to 10 microM) inhibited NO production
      without exerting detectable cytotoxicity. F, K, and Q dose-dependently repressed
      iNOS mRNA expression and prostaglandin E2 (PGE2) production, in part through an
      attenuating NF-kappaB signaling pathway. This result indicates that flavonols,
      despite structural similarity, have different antioxidant and antiinflammatory
      effects.

PMID- 17177505
TI  - Antiangiogenic activity of brown algae fucoxanthin and its deacetylated product,
      fucoxanthinol.
AB  - The antiangiogenic effects of fucoxanthin and a deacetylated product,
      fucoxanthinol, were examined. Fucoxanthin significantly suppressed HUVEC
      proliferation and tube formation at more than 10 microM, but it had no
      significant effect on HUVEC chemotaxis. The formation of blood vessel-like
      structures from CD31-positive cells was evaluated using embryonic stem cell
      derived embryoid bodies. Fucoxanthin effectively suppressed the development of
      these structures at 10-20 microM, suggesting that it could suppress
      differentiation of endothelial progenitor cells into endothelial cells involving
      new blood vessel formation. Fucoxanthin and fucoxanthinol suppressed microvessel
      outgrowth in an ex vivo angiogenesis assay using a rat aortic ring, in a dose
      dependent manner. These results imply that fucoxanthin having antiangiogenic
      activity might be useful in preventing angiogenesis-related diseases.

PMID- 17177506
TI  - Pharmacokinetics of cycloalliin, an organosulfur compound found in garlic and
      onion, in rats.
AB  - Cycloalliin, an organosulfur compound found in garlic and onion, has been
      reported to exert several biological activities and also to remain stable during
      storage and processing. In this study, we investigated the pharmacokinetics of
      cycloalliin in rats after intravenous or oral administration. Cycloalliin and its
      metabolite, (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid, in plasma, urine,
      feces, and organs was determined by a validated liquid chromatography-mass
      spectrometry method. When administered intravenously at 50 mg/kg, cycloalliin was
      rapidly eliminated from blood and excreted into urine, and its total recovery in
      urine was 97.8% +/- 1.3% in 48 h. After oral administration, cycloalliin appeared
      rapidly in plasma, with a tmax of 0.47 +/- 0.03 h at 25 mg/kg and 0.67 +/- 0.14 h
      at 50 mg/kg. Orally administered cycloalliin was distributed in heart, lung,
      liver, spleen, and especially kidney. The Cmax and AUC0-inf values of cycloalliin
      at 50 mg/kg were approximately 5 times those at 25 mg/kg. When administered
      orally at 50 mg/kg, cycloalliin was excreted into urine (17.6% +/- 4.2%) but not
      feces. However, the total fecal excretion of (3R,5S)-5-methyl-1,4-thiazane-3
      carboxylic acid was 67.3% +/- 5.9% (value corrected for cycloalliin equivalents).
      In addition, no (3R,5S)-5-methyl-1,4-thiazane-3-carboxylic acid was detected in
      plasma (<0.1 microg/mL), and negligible amounts (1.0% +/- 0.3%) were excreted
      into urine. In in vitro experiments, cycloalliin was reduced to (3R,5S)-5-methyl
      1,4-thiazane-3-carboxylic acid during anaerobic incubation with cecal contents of
      rats. These data indicated that the low bioavailability (3.73% and 9.65% at 25
      and 50 mg/kg, respectively) of cycloalliin was due mainly to reduction to (3R,5S)
      5-methyl-1,4-thiazane-3-carboxylic acid by the intestinal flora and also poor
      absorption in the upper gastrointestinal tract. These findings are helpful for
      understanding the biological effects of cycloalliin.

PMID- 17177507
TI  - Sources of antioxidant activity in Australian native fruits. Identification and
      quantification of anthocyanins.
AB  - Selected native Australian fruits, muntries (Kunzea pomifera F. Muell.,
      Myrtaceae), Tasmanian pepper berry (Tasmanian lanceolata R. Br., Winteraceae),
      Illawarra plum (Podocarpus elatus R. Br. ex Endl., Podocarpaceae), Burdekin plum
      (Pleiogynium timorense DC. Leenh, Anacardiaceae), Cedar Bay cherry (Eugenia
      carissoides F. Muell., Myrtaceae), Davidson's plum (Davidsonia pruriens F. Muell.
      var. pruriens, Davidsoniaceae), and Molucca raspberry (Rubus moluccanus var.
      austropacificus van Royen, Rosaceae), were evaluated as sources of antioxidants
      by 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays and
      compared with blueberry (Vaccinum spp. cv. Biloxi). The total reducing capacity
      of five fruits was 3.5-5.4-fold higher than that of blueberry, and the radical
      scavenging activities of muntries and Burdekin plum were 1.5- and 2.6-fold
      higher, respectively. The total phenolic level by Folin-Ciocalteu assay highly
      correlated with the antioxidant activity. Therefore, systematic research was
      undertaken to identify and characterize phenolic complexes. In the present study
      we report on the levels and composition of anthocyanins. The HPLC-DAD and
      HPLC/ESI-MS-MS (ESI = electrospray ionization) analyses revealed simple
      anthocyanin profiles of one to four individual pigments, with cyanidin as the
      dominating type. This is the first evaluation of selected native Australian
      fruits aiming at their utilization for the development of novel functional food
      products.

PMID- 17177508
TI  - Identification and kinetic study of tyrosinase inhibitors found in sake lees.
AB  - The present study found that the n-hexane extract of freeze-dried sake lees
      inhibits tyrosinase activity and showed that the constituents isolated from the n
      hexane extract are the mixture of triacylglycerols. The inhibitory effects of
      triolein and trilinolein found as the triacylglycerols were examined using
      tyrosinases from mushroom and Streptomyces castaneoglobisporus. The IC50 values
      of the triacylglycerol mixture for the oxidase activity on mushroom and
      Streptomyces tyrosinases were 20 and 0.14 microg/mL, respectively. The IC50
      values of trilinolein for the oxidase activity on mushroom and Streptomyces
      tyrosinases were 8.4 and 0.1 microM, respectively. However, the inhibitory effect
      of triolein (IC50=30 microM) was lower than that of trilinolein, even when the
      Streptomyces tyrosinase was used for the assay. Kinetic analyses indicate that
      both trilinolein and triolein inhibit the tyrosinase activity noncompetitively.
      When transformed with a plasmid carrying the Streptomyces tyrosinase gene, the
      melanin-synthesizing ability of the transformed Escherichia coli host was dose
      dependently interfered with by trilinolein.

PMID- 17177509
TI  - Characterization of phenolic compounds from lingonberry (Vaccinium vitis-idaea).
AB  - Phenolic compounds from the lingonberry (Vaccinium vitis-idaea) were identified
      using LC-TOFMS, LC-MS/MS, and NMR experiments. The compounds were extracted from
      the plant material using methanol in an ultrasonicator and further isolated and
      purified using solid-phase extraction and preparative liquid chromatographic
      techniques. A total of 28 phenolic compounds were at least tentatively
      identified, including flavonols, anthocyanidins, catechins and their glycosides,
      and different caffeoyl and ferulic acid conjugates. This is apparently the first
      report of coumaroyl-hexose-hydroxyphenol, caffeoyl-hexose-hydroxyphenol,
      coumaroyl-hexose-hydroxyphenol, quercetin-3-O-alpha-arabinofuranoside, kaempferol
      pentoside, and kaempferol-deoxyhexoside in the plant, and the flavonol
      acylglycosides quercetin-3-O-[4' '-(3-hydroxy-3-methylglutaroyl)]-alpha-rhamnose
      and kaempferol-3-O-[4' '-(3-hydroxy-3-methylglutaroyl)]-alpha-rhamnose are
      presented here for the first time ever. In addition, more detailed structure in
      comparison to earlier reports is described for some compounds previously known to
      exist in lingonberry.

PMID- 17177510
TI  - New herbicide models from benzoxazinones: aromatic ring functionalization
      effects.
AB  - The utility of benzoxazinones and some of their synthetic derivatives in the
      search for new leads for herbicide model development has been widely discussed.
      As the benzoxazinone skeleton contains three different potential areas for
      functionalization (C-2, N-4, and aromatic protons H-5, H-6, H-7, and H-8), and
      the first two have already been optimized, the main objective of this work was
      the substitution of aromatic protons for different substituent types and the
      study of the effects of the prepared chemicals on selected standard target
      species (STS) and weeds. Thus, different combinations of aromatic substituents,
      including methoxy, methoxycarbonyl, fluorine, chlorine, and trifluoromethyl, were
      introduced at different positions. Phytotoxicity results were successfully
      correlated with steric and electronic molecular parameters, the resulting
      molecular volume (V) and dipole moment (mu) being the most influential ones.
      Halogenations at C-6 and fluorination at C-7 were the most successful
      modifications. Compounds 6-fluoro-(2H)-1,4-benzoxazin-3(4H)-one (6F-D-DIBOA), 7
      fluoro-(2H)-1,4-benzoxazin-3(4H)-one (7F-D-DIBOA), and 6-chloro-(2H)-1,4
      benzoxazin-3(4H)-one (6Cl-D-DIBOA) had the highest phytotoxic activities. The
      dose-response profiles on wheat and two of its most common weeds (Lolium rigidum
      Gaud. and Avena fatua L.) were compared by means of a proposed selectivity index,
      which displayed 7F-D-DIBOA as the most selective of the tested benzoxazinones.

PMID- 17177512
TI  - Chemical modification of wheat protein-based natural polymers: cross-linking
      effect on mechanical properties and phase structures.
AB  - Chemical modification of wheat protein-based natural polymer materials was
      conducted using glyoxal as cross-linker, and the cross-linking effect was studied
      on mechanical properties under different humidity conditions, the molecular
      motions of each component, and the phase structures/components of the whole
      materials. The cross-linking significantly enhanced the mechanical strength of
      wheat gluten (WG) materials under RH = 50%. The elongation of materials was also
      increased, which was in contrast to many cross-linked protein systems. The
      reaction mainly occurred in proteins and starch components, resulting in the
      formation of a stable cross-linked network with restricted molecular motions and
      modified motional dynamics. Although the plasticizer glycerol could also take
      part in the reaction with glyoxal or other components in WG especially when the
      glyoxal content was higher, the amount of glycerol involved in such reactions was
      very little. Glycerol was predominantly hydrogen-bonded with the network. The
      lipid component did not seem to take part in the cross-linking reaction; its
      mobility was promoted while its interaction with the protein-starch network was
      weakened after cross-linking. The formation of the cross-linked network did not
      enhance the hydrophobicity of the materials; the materials still adsorbed a high
      level of moisture under high humidity conditions (ca. RH = 85%) with no
      improvement in mechanical strength. In addition, further increasing the amount of
      glyoxal did not generate an additional strength improvement even at RH = 50%,
      possibly because the enhanced mobility of lipid promoted the component to be
      phase-separated from the WG system. To improve the water-resistant properties,
      the hydrophobicity of the protein macromolecules requires enhancement by other
      chemical modifications.

PMID- 17177513
TI  - Synthesis of hydroxy thio-ether derivatives of vegetable oil.
AB  - Bio-based additives are desirable commodities due to their eco-friendly nature.
      These additives can demonstrate physical and chemical properties comparable to
      those of conventional mineral oil-based products. Sulfur incorporated
      triacylglycerol can function as an antiwear/antifriction additive for lubricants.
      The synthesis of four useful hydroxy thio-ether derivatives of vegetable oils,
      from commercially available epoxidized soybean oil and common organic thiols, is
      reported in this paper. The common thiols used herein were 1-butanethiol, 1
      decanethiol, 1-octadecanethiol, and cyclohexyl mercaptan. Currently, there is no
      reported literature describing the synthesis of hydroxy thio-ether derivatives of
      vegetable oil. The reaction was monitored, and products were confirmed by NMR and
      FTIR spectroscopies. Experimental conditions involving various thiols, solvent,
      catalyst amount, time, and temperature were optimized for research quantity and
      laboratory scale-up. The synthetic process retains the vegetable oil structure,
      eliminates polyunsaturation in the molecule, and adds polar functional groups on
      triacylglycerol. These products can be used as agriculturally-based antiwear
      additives for lubricant applications.

PMID- 17177514
TI  - Glucan and fructan production by sourdough Weissella cibaria and Lactobacillus
      plantarum.
AB  - After a large screening on sourdough lactic acid bacteria, exopolysaccharide
      (EPS)-forming strains of Weissella cibaria, Lactobacillus plantarum, and
      Pediococcus pentosaceus were selected. After 6 days of incubation at 30 degrees
      C, the synthesis of EPS in MRS-based broth ranged from 5.54 to 7.88 mg mL-1. EPS
      had an apparent molecular mass of ca. 104 Da. As shown by carbohydrate
      consumption, the synthesis of EPS was found from sucrose only. Two types of
      homopolysaccharides were synthesized: glucans simultaneously with growth and
      fructans after 1 day of incubation. Two protein bands of ca. 180-200 kDa were in
      situ detected on SDS-PAGE gels incubated with sucrose. PCR products of ca. 220 bp
      were found for L. plantarum PL9 (100% of identity to putative priming
      glycosyltransferase of L. plantarum WCFS1) and W. cibaria WC4 (80% of identity to
      putative glycosyltransferase, epsD, of Bacillus cereus G9241) by using hybrid
      primers for the priming gtf genes. Degenerated primers DexreuR and DexreuV showed
      a unique PCR product, and the predicted amino acid sequences were identical for
      W. cibaria WC4 and L. plantarum PL9. The sequence had similarity with
      polysaccharide biosynthesis glycosyltransferases. W. cibaria WC4 or L. plantarum
      LP9 synthesized ca. 2.5 g kg-1 EPS during sourdough fermentation with sucrose
      added. Compared to the sourdough started with an EPS-negative strain, the
      sourdough started with W. cibaria WC4 or L. plantarum LP9 increased the
      viscosity, and the resulting bread had higher specific volume and lower firmness.
      The synthesis of EPS by selected sourdough lactic acid bacteria could be
      considered as a useful tool to replace the additives for improving the textural
      properties of baked goods.

PMID- 17177511
TI  - Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed
      competitive ligand and partial agonist at the human mu opiate receptor.
AB  - Black cohosh is a commonly used botanical dietary supplement for the treatment of
      climacteric complaints. Because the opiate system in the brain is intimately
      associated with mood, temperature, and sex hormonal levels, the activity of black
      cohosh extracts at the human mu opiate receptor (hMOR) expressed in Chinese
      hamster ovary cells was investigated. The 100% methanol, 75% ethanol, and 40% 2
      propanol extracts of black cohosh effectively displaced the specific binding of
      [3H]DAMGO to hMOR. Further studies of the clinically used ethanol extract
      indicated that black cohosh acted as a mixed competitive ligand, displacing 77 +/
      4% [3H]DAMGO to hMOR (Ki = 62.9 microg/mL). Using the [35S]GTPgammaS assay, the
      action of black cohosh was found to be consistent with an agonist, with an EC50
      of 68.8 +/- 7.7 microg/mL. These results demonstrate for the first time that
      black cohosh contains active principle(s) that activate hMOR, supporting its
      beneficial role in alleviating menopausal symptoms.

PMID- 17177515
TI  - Improving potato storage and processing characteristics through all-native DNA
      transformation.
AB  - The dominant potato (Solanum tuberosum) variety for French fry production in the
      United States is the 131-year-old Russet Burbank. Market penetration of the
      higher yielding and more uniform Ranger Russet variety is limited to about one
      fifth of that of the Russet Burbank because of two storage deficits: black spot
      bruise sensitivity and high levels of cold-induced sweetening. Here, these trait
      weaknesses are turned into strengths by simultaneously lowering the expression of
      Ranger Russet's tuber-expressed polyphenol oxidase (Ppo), starch-associated R1,
      and phosphorylase-L (PhL) genes. This genetic modification was accomplished
      without inserting any foreign DNA into the plant genome. French fries from the
      intragenic potatoes also contained reduced amounts of the antinutritional
      compound acrylamide while, unexpectedly, displaying enhanced sensory
      characteristics.

PMID- 17177516
TI  - Purification and characterization of windmill palm tree (Trachycarpus fortunei)
      peroxidase.
AB  - High peroxidase activity was demonstrated to be present in the leaf of several
      species of cold-resistant palms. Histochemical studies of the leaf of windmill
      palm tree (Trachycarpus fortunei) showed the peroxidase activity to be localized
      in hypoderma, epidermis, cell walls, and conducting bundles. However, chlorophyll
      containing mesophyll cells had no peroxidase at all. The leaf windmill palm tree
      peroxidase (WPTP) was purified to homogeneity and had a specific activity of 6230
      units/mg, RZ = 3.0, a molecular mass of 50 kDa, and an isoelectric point of pI
      3.5. The electronic spectrum of WPTP with a Soret band at 403 nm was typical of
      plant peroxidases. The N-terminal amino acid sequence of WPTP was determined. The
      substrate specificity of WPTP was distinct from that of other palm peroxidases,
      and the best substrate for WPTP was 2,2'-azinobis(3-ethylbenzthiazoline-6
      sulfonic acid). The palm peroxidase showed an unusually high stability at
      elevated temperatures and high concentrations of guanidine.

PMID- 17177517
TI  - Hyperproduction and application of alpha-agarase to enzymatic enhancement of
      antioxidant activity of porphyran.
AB  - The nucleotide sequence of the gene for the alpha-agarase, AgaA33, from
      Thalassomonas sp. strain JAMB-A33 was determined. The open reading frame for
      AgaA33 was revealed to encode 1463 amino acid residues. We succeeded in
      extracellular production of recombinant -agarase (AgaA33) efficiently using
      Bacillus subtilis as a host. This is the first report of recombinant production
      of -agarase. Furthermore, we demonstrated that hydrolysis of alpha-1,3 linkages
      in porphyran, a sulfated polysaccharide from marine red algae, by alpha-agarase
      is an important step for improvement of its antioxidant activity with regard to
      free-radical-scavenging capacity and superoxide radical anion scavenging
      activity, whereas the hydrolysis of beta-1,4 linkages in porphyran by beta
      agarase did not increase on the antioxidant activity markedly.

PMID- 17177518
TI  - Biochemical safety evaluation of transgenic rice seeds expressing T cell epitopes
      of Japanese cedar pollen allergens.
AB  - Transgenic rice seeds, which express a hybrid peptide comprising seven
      predominant human T cell epitopes (7Crp) derived from Japanese cedar pollen
      allergens, have been shown to function as an effective edible vaccine for the
      control of pollen allergen-induced responses. In this study, we characterized
      biochemical properties of transgenic seeds expressing the 7Crp peptide. The
      levels of chemical compositions, such as carbohydrate, protein, lipid, amino
      acid, fatty acid, mineral, and vitamin, were substantially equivalent between
      transgenic 7Crp and its nontransgenic counterpart seeds. The contents of three
      major allergenic proteins in transgenic seeds were not enhanced by expression of
      the 7Crp peptide when compared with those of nontransgenic seeds. The 7Crp
      peptide expressed in seeds was susceptible to simulated gastric/intestinal
      fluids. N-Glycosylation was not observed in the 7Crp peptide sequence. These
      results indicate that transgenic 7Crp seeds are substantially equivalent to
      nontransgenic parental seeds except for the presence of the 7Crp peptide.
      KEYWORDS: Food safety assessment; transgenic rice seed; edible vaccine; peptide
      based immunotherapy; Japanese cedar pollinosis.

PMID- 17177519
TI  - Production of high hydroxytyrosol yields via tyrosol conversion by Pseudomonas
      aeruginosa immobilized resting cells.
AB  - An immobilized whole cell system was successfully performed to produce the most
      powerful antioxidant, hydroxytyrosol. Bioconversion of tyrosol into
      hydroxytyrosol was achieved via the immobilization of Pseudomonas aeruginosa
      resting cells in calcium alginate beads. Immobilization was advantageous as it
      allows immobilized cells to tolerate a greater tyrosol concentration than free
      cells. The bioconversion yield reached 86% in the presence of 5 g L-1 of tyrosol
      when cells immobilized in alginate beads were carried out in single batches.
      Evaluation of kinetic parameters showed the maintenance of the same catalytic
      efficiency expressed as Kcat/Km for both free and immobilized cells. The use of
      immobilized cells in repeated batches demonstrated a notable activity
      stabilization since the biocatalyst reusability was extended for at least four
      batches with a molar yield greater than 85%.

PMID- 17177520
TI  - Effects of pressurization on structure, water distribution, and sensory
      attributes of cured ham: can pressurization reduce the crucial sodium content?
AB  - This study investigated the replacement of tumbling (intermittent vacuum tumbling
      for 6 h) with pressure treatment (7 MPa for 4 s) in the production of a cured ham
      product with the aim of elucidating if the pressure treatment could reduce the
      amount of salt added to obtain a satisfactory product. Confocal laser scanning
      microscopy (CLSM) revealed a pressure-induced loosening of the meat structure,
      and proton nuclear magnetic resonance (NMR) relaxometry revealed that this
      structural modification of the meat had an impact on water properties and water
      distribution in both cooked and cooked/fried products. Three salt levels (0.6,
      1.1, and 1.7% w/w) were investigated, and sensory profiling revealed that the
      pressured-cooked meat obtained a significantly higher juiciness score at low and
      medium salt levels. In addition, sensory profiling assessments revealed that at
      the lowest salt concentration the pressured product was perceived to be saltier
      compared with the tumbled product; however, the difference was not significant
      and was absent upon frying. In contrast, in sensory time intensity analysis the
      maximum intensity and the total salt taste were significantly higher in the
      pressured samples at the low and medium salt levels in the cooked samples. In
      conclusion, the present study showed strong evidence that the structure and
      biophysical characteristics of cured ham is altered by pressurization and
      suggested that pressurization may reduce the critical amount of salt required in
      a ham product.

PMID- 17177521
TI  - Effects of must concentration techniques on wine isotopic parameters.
AB  - Despite the robustness of isotopic methods applied in the field of wine control,
      isotopic values can be slightly influenced by enological practices. For this
      reason, must concentration technique effects on wine isotopic parameters were
      studied. The two studied concentration techniques were reverse osmosis (RO) and
      high-vacuum evaporation (HVE). Samples (must and extracted water) have been
      collected in various French vineyards. Musts were microfermented at the
      laboratory, and isotope parameters were determined on the obtained wine.
      Deuterium and carbon-13 isotope ratios were studied on distilled ethanol by
      nuclear magnetic resonance (NMR) and isotope ratio mass spectrometry (IRMS),
      respectively. The oxygen-18 ratio was determined on extracted and wine water
      using IRMS apparatus. The study showed that the RO technique has a very low
      effect on isotopic parameters, indicating that this concentration technique does
      not create any isotopic fractionation, neither at sugar level nor at water level.
      The effect is notable for must submitted to HVE concentration: water evaporation
      leads to a modification of the oxygen-18 ratio of the must and, as a consequence,
      ethanol deuterium concentration is also modified.

PMID- 17177522
TI  - Impact of browning reactions and bran pigments on color of parboiled rice.
AB  - Rice color changes from white to amber during parboiling (soaking and steaming).
      Color parameters indicated that, during soaking, yellow bran pigments leached out
      in the water. The levels of the Maillard precursors (i.e., reducing sugars (RS)
      and free alpha-amino nitrogen (FAN)) depended on soaking temperature and time:
      leaching of RS was compensated by enzymic formation for long soaking times (>60
      min), while proteolytic activity was too low to compensate for FAN leaching. Rice
      soaking under nitrogen, oxygen, or ambient conditions and determination of
      polyphenol oxidase activity allowed us to conclude that the effect of enzymic
      color changes on the soaked rice color was rather small. Color measurements of
      brown and milled mildly, intermediately, and severely parboiled rice samples
      showed that both brown and milled rice samples were darker and more red and
      yellow after parboiling and that the effect depended on the severity of
      parboiling conditions. Furthermore, steaming affected the rice color more and in
      a way opposite to that observed in soaking. The changes in RS and the loss of FAN
      during parboiling suggested that Maillard type reactions occur during brown rice
      steaming. Analyses of furosine levels confirmed Maillard browning of outer bran
      layers and endosperm during steaming. The level of this Maillard indicator
      increased with the severity of parboiling conditions in both brown and milled
      parboiled rice. Measurements of the levels of bran pigments indicated that bran
      pigments diffuse into the endosperm during parboiling and contribute to the
      parboiled rice color.

PMID- 17177523
TI  - Influence of cultivar and processing on cherry (Prunus avium) allergenicity.
AB  - Oral allergy syndrome is an immediate food allergic event that affects lips,
      mouth, and pharynx, is often triggered by fruits and vegetables, and may be
      associated with pollinosis. Here, we report on the allergenic pattern of
      different varieties of cherry (Prunus avium) and results obtained by applying
      several technological processes to the selected varieties. Whole cherries were
      submitted to chemical peeling, thermal treatment, and syruping processes, and the
      relative protein extracts were analyzed by in vitro (sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and immunoblotting analysis) and in vivo tests
      (skin prick test). Electrophoretic analyses demonstrated that there was no marked
      difference among cherry cultivars. Chemical peeling successfully removed Pru av
      3, a lipid transfer protein (LTP) responsible for oral allergy syndrome in
      patients without pollinosis, leading to the industrial production of cherry
      hypoallergenic derivatives. Furthermore, the syruping process removed almost all
      allergenic proteins to whom patients with pollinosis are responsive. In vivo
      tests confirmed electrophoretic results.

PMID- 17177524
TI  - Steamed American ginseng berry: ginsenoside analyses and anticancer activities.
AB  - This study was designed to determine the changes in saponin content in American
      ginseng berries after treatment by heating and to assess the anticancer effects
      of the extracts. After steaming treatment (100-120 degrees C for 1 h, and 120
      degrees C for 0.5-4 h), the content of seven ginsenosides, Rg1, Re, Rb1, Rc, Rb2,
      Rb3, and Rd, decreased; the content of five ginsenosides, Rh1, Rg2, 20R-Rg2, Rg3,
      and Rh2, increased. Rg3, a previously identified anticancer ginsenoside,
      increased significantly. Two hours of steaming at 120 degrees C increased the
      content of ginsenoside Rg3 to a greater degree than other tested ginsenosides.
      When human colorectal cancer cells were treated with 0.5 mg/mL steamed berry
      extract (120 degrees C 2 h), the antiproliferation effects were 97.8% for HCT-116
      and 99.6% for SW-480 cells. At the same treatment concentration, the effects of
      unsteamed berry extract were 34.1% for HCT-116 and 4.9% for SW-480 cells. After
      staining with Hoechst 33258, apoptotic cells increased significantly by treatment
      with steamed berry extract compared with unheated extracts. Induction of
      apoptosis activity was confirmed by flow cytometry after staining with annexin
      V/PI. The steaming of American ginseng berries augments ginsenoside Rg3 content
      and increases the antiproliferative effects on two human colorectal cancer cell
      lines.

PMID- 17177525
TI  - Application of far-infrared irradiation in the manufacturing process of green
      tea.
AB  - Seven kinds of green tea leaves were manufactured with far-infrared (FIR)
      irradiation, and the physicochemical characteristics of the green tea were
      determined. Appropriate FIR irradiation during the manufacturing process
      significantly increased the polyphenolic content of green tea. FIR irradiation at
      90 degrees C for 10 min, replacing the roasting step, and of the fully processed
      green tea leaves (GTP3) increased the total phenol content of green tea from
      475.6 to 811.1 mg/g and the total flavanol content from 175.7 to 208.7 mg/g, as
      compared to the control. Epigallocatechin and epigallocatechin gallate increased
      from 57.68 and 9.60 mg/g in a nonirradiated control to 89.88 and 16.33 mg/g in
      GTP3, respectively. Ascorbic acid, caffeine, and nitrite scavenging activities
      were also increased in GTP3. However, the overall color change of GTP3 was
      negligible. These results indicate that the chemical properties of green tea are
      significantly affected by FIR irradiation at specific stages of the manufacturing
      process of green tea leaves and that this FIR irradiation results in high-quality
      green tea.

PMID- 17177526
TI  - Effects of domestic processing on steroidal saponins in Taiwanese yam cultivar
      (Dioscorea pseudojaponica Yamamoto).
AB  - The effects of domestic processing on steroidal saponins and furostanol and
      spirostanol glycosides in Taiwanese yam cultivar (Dioscorea pseudojaponica
      Yamamoto) were studied. The baking or frying of yam slices was conducted at 150,
      180, and 200 degrees C for 3, 5, and 10 min. Yam slices were steamed or microwave
      cooked at 2450 MHz with an output power of 850 W for 3, 5, and 10 min. The
      various saponins were quantified by HPLC with an evaporative light scattering
      detector (ELSD). Results showed that the contents of saponins were decreased
      along with increasing cooking temperature and time except for the steaming
      treatment. None of the steamed yam slices significantly change their initial
      compositions or quantities of furostanol and spirostanol glycosides. Fried yam
      slices had the highest loss of saponins, especially at 200 degrees C for 10 min
      (93 and 97% reductions for total furostanol and spirostanol glycosides,
      respectively). After baking for 10 min at 200 degrees C, the total furostanol and
      spirostanol glycosides were reduced by 67 and 74%, respectively. There were 12,
      44, and 84% decreases for total furostanol glycosides and 10, 35, and 75%
      reductions for total spirostanol glycosides in yam slices after microwave cooking
      for 3, 5, and 10 min, respectively. Diosgenin, the aglycone of these saponins,
      could be found in yams after microwave cooking and baking, but not in steamed and
      fried yams.

PMID- 17177527
TI  - Comparative study of protein stabilization in white wine using zirconia and
      bentonite: physicochemical and wine sensory analysis.
AB  - A semi-industrial application of the continuous stabilization of white wine
      protein using a column packed with zirconia was studied and compared to the
      traditional bentonite treatment using a Macabeu white wine. Physicochemical and
      wine sensory properties were evaluated using a rating system and triangle tests.
      Continuous protein stabilization was analyzed in three residence times, and the
      equivalent of 300 BV of wine was used for both treatments. Wine protein content
      was reduced by 21%, 40%, and 42% using the continuous process with residence
      times of 7.5, 15, and 30 min, respectively, and by 61.4% using the bentonite
      treatment. The wines obtained from the packed column were protein stable up to
      25, 75, and 175 BV for residence times of 7.5, 15, and 30 min, respectively. The
      amount of polyphenol removed was less than 10%, and similar amounts were removed
      from the wine regardless of residence time, while 20.6% of polyphenol was removed
      using bentonite. The physicochemical and sensory properties of wine treated with
      bentonite were similar to those of wine treated with zirconia.

PMID- 17177528
TI  - Biogenic amine formation and nitrite reactions in meat batter as affected by high
      pressure processing and chilled storage.
AB  - Changes in biogenic amine formation and nitrite depletion in meat batters as
      affected by pressure-temperature combinations (300 MPa/30 min/7, 20, and 40
      degrees C), cooking process (70 degrees C/30 min), and storage (54 days/2 degrees
      C) were studied. Changes in residual nitrite concentration in raw meat batters
      were conditioned by the temperature and not by the pressure applied. Cooking
      process decreased (P < 0.05) the residual nitrite concentration in all samples.
      High-pressure processing and cooking treatment increased (P < 0.05) the nitrate
      content. Whereas protein-bound nitrite concentration decreased with pressure
      processing, no effect was observed with the heating process of meat batters. High
      pressure processing conditions had no effect on the rate of residual nitrite loss
      throughout the storage. The application of high pressure decreased (P < 0.05) the
      concentration of some biogenic amines (tyramine, agmatine, and spermine).
      Irrespective of the high processing conditions, generally, throughout storage
      biogenic amine levels did not change or increased, although quantitatively this
      effect was not very important.

PMID- 17177529
TI  - Flavonoid content of U.S. fruits, vegetables, and nuts.
AB  - Analytical data are reported for 20 flavonoids (as aglycones) determined for more
      than 60 fresh fruits, vegetables, and nuts collected from four regions across the
      United States at two times of the year. Sample collection was designed and
      implemented by the Nutrient Data Laboratory (USDA). Analyses of eight flavan-3
      ols (catechin, catechin gallate, epicatechin, epicatechin gallate,
      epigallocatechin, epigallocatechin gallate, gallocatechin, and gallocatechin
      gallate), six anthocyanins (cyanidin, delphinidin, malvidin, pelargonidin,
      peonidin, and petunidin), two flavanones (hesperetin and naringenin), two
      flavones (apigenin and luteolin), and two flavonols (myricetin and quercetin)
      were performed by the Food Composition Laboratory (USDA) using a hydrolysis
      method for the anthocyanidins, flavones, and flavonols and a direct extraction
      method for the flavan-3-ols and flavanones. Experimental results compare
      favorably (few statistically significant differences) to literature values in the
      flavonoid and proanthocyanidin database previously compiled by the Nutrient Data
      Laboratory. The results of this study showed a seasonal variation only for
      blueberries. This study also showed that the variation in the flavonoid content
      of foods, as purchased by the U.S. consumer, is very large. The relative standard
      deviation, averaged for each flavonoid in each food, was 168%.

PMID- 17177530
TI  - Phenolic compounds of barley grain and their implication in food product
      discoloration.
AB  - Barley grains contain significant amounts of phenolic compounds that may play a
      major role in the discoloration of food products. Phenolic acid and
      proanthocyanidin (PA) composition of 11 barley genotypes were determined, using
      high-performance liquid chromatography and liquid chromatography-mass
      spectrometry, and their significance on food discoloration was evaluated. Abraded
      grains contained 146-410 microg/g of phenolic acids (caffeic, p-coumaric, and
      ferulic) in hulled barley and 182-282 microg/g in hulless barley. Hulled PA
      containing and PA-free genotypes had comparable phenolic acid contents. Catechin
      and six major barley PAs, including dimeric prodelphinidin B3 and procyandin B3,
      and four trimers were quantified. PAs were quantified as catechin equivalents
      (CE). The catechin content was higher in hulless (48-71 microg/g) than in hulled
      (32-37 microg/g) genotypes. The total PA content of abraded barley grains ranged
      from 169 to 395microg CE/g in PA-containing hulled and hulless genotypes. Major
      PAs were prodelphinidin B3 (39-109 microg CE/g) and procyanidin B3 (40-99 microg
      CE/g). The contents of trimeric PAs including procyanidin C2 ranged from 53 to
      151 g CE/g. Discoloration of barley flour dough correlated with the catechin
      content of abraded grains (r = -0.932, P < 0.001), but not with the content of
      individual phenolic acids and PAs. Discoloration of barley flour dough was,
      however, intensified when total PA extracts and catechin or dimeric PA fractions
      were added into PA-free barley flour. The brightness of dough also decreased when
      the total PA extract or trimeric PA fraction was added into heat-treated PA-free
      barley flour. Despite its low concentration, catechin appears to exert the
      largest influence on the discoloration of barley flour dough among phenolic
      compounds.

PMID- 17177531
TI  - Chemometrical characterization of four italian rice varieties based on genetic
      and chemical analyses.
AB  - This paper describes a method for achieving qualitative identification of four
      rice varieties from two different Italian regions. To estimate the presence of
      genetic diversity among the four rice varieties, we used polymerase chain
      reaction-randomly amplified polymorphic DNA (PCR-RAPD) markers, and to elucidate
      whether a relationship exists between the ground and the specific characteristics
      of the product, we studied proximate composition, fatty acid composition, mineral
      content, and total antioxidant capacity. Using principal component analysis on
      genomic and compositional data, we were able to classify rice samples according
      to their variety and their district of production. This work also examined the
      discrimination ability of different parameters. It was found that genomic data
      give the best discrimination based on varieties, indicating that RAPD assays
      could be useful in discriminating among closely related species, while
      compositional analyses do not depend on the genetic characters only but are
      related to the production area.

PMID- 17177532
TI  - Production and composition of cider spirits distilled in "alquitara".
AB  - The capacity of alquitara (a traditional distillation system) to produce cider
      brandies is evaluated. To do so, the chemical composition of 12 fractions
      obtained during the distillation process and the cider brandies obtained from
      five ciders were analyzed (alcohol strength, methanol, volatile substances,
      furfural, and metals), taking into account European and Spanish legislation.
      During the course of distillation, an important increase in methanol, furfural, 2
      phenylethanol, and metals in the last fractions was observed, while fusel oils
      were more abundant in the first fractions collected. Only acetaldehyde behaved
      differently, showing a minimum concentration in the middle fractions that might
      be explained by its formation on the surface of alquitara. On the other hand, the
      final distillates obtained by means of this method complied with the considered
      regulations. Worth highlighting in this regard are the low levels of a potential
      toxin such as methanol, as well as the detection of a constant ratio for
      methanol, ethanol, and fusel oil for the pairs of cider/spirits analyzed, which
      could be interpreted as an indication of good uniformity in the distillation
      system and method, thus guaranteeing product quality.

PMID- 17177533
TI  - Difference in folate content of green and red sweet peppers (Capsicum annuum)
      determined by liquid chromatography-mass spectrometry.
AB  - Folic acid (pteroylmonoglutamic acid) is used in enriched foods; however, very
      little folic acid occurs naturally in fruits and vegetables. For the U.S.
      Department of Agriculture's National Food and Nutrient Analysis Program, a number
      of fruits and vegetables have been assayed for endogenous folates, by a liquid
      chromatography-mass spectrometry method, to evaluate the accuracy of existing
      data for total folate determined by standard microbiological analysis. Folate in
      red and green sweet peppers (Capsicum annuum) differed notably (70.2 and 20.7
      microg/100 g, respectively) and exceeded existing values determined by
      microbiological assay (18 and 11 microg/100 g, respectively). 5
      Methyltetrahydrofolate was the predominant vitamer, but a significant amount of 5
      formyltetrahydrolfolate and some 10-formylfolate were present. These findings may
      assist in making dietary recommendations or developing research diets related to
      folate. The data from this study have been used to update the folate values in
      release 19 of the USDA Nutrient Database for Standard Reference.

PMID- 17177534
TI  - Evaluation of soyasaponin, isoflavone, protein, lipid, and free sugar
      accumulation in developing soybean seeds.
AB  - A combination of analytical techniques was used to examine and quantify seed
      compositional components such as protein, lipid, free sugars, isoflavones, and
      soyasaponins during soybean development and maturation in two Korean soybean
      cultivars. Protein accumulation was rapid during reproductive stages, while lipid
      content was only relatively moderately increased. The major carbohydrate
      saccarides sucrose and stachyose constantly increased during the reproductive
      stage. Previously published results suggest that the free sugar and lipid content
      reached their maximal concentrations at a relatively early stage of seed
      development and remain constant in comparison to other chemical components. The
      malonylglucosides were the predominant isoflavone form followed by the
      glucosides, acetyl glucosides, and aglycone forms. As soybean seed matures, total
      soyasaponin concentration was constantly decreased until the R8 stage.
      Soyasaponin beta(g) was the major soyasaponin in DDMP-conjugated group B
      soyasaponins, followed by the non-DDMP counterpart soyasaponin I and soyasaponin
      A1. The ratio of total isoflavone to total soyasaponin in the developing soybean
      increased from 0.06 to 1.31. Protein, lipid, and free sugar contents in the
      developing soybean seeds showed significant positive correlations with conjugated
      isoflavones and total isoflavone concentration, while the lipid contents showed a
      negative correlation with the isoflavone aglycone. Protein, lipid, and free sugar
      contents showed a negative correlation with total group A and B soyasaponins and
      total soyasaponins; however, only the soyasaponin A content was significantly
      negatively correlated with free sugar content. Total soyasaponin content was
      negatively correlated with isoflavone content (r = -0.828 at p < 0.01).

PMID- 17177535
TI  - Metalloporphyrins as biomimetic models for cytochrome p-450 in the oxidation of
      atrazine.
AB  - The aim of this work was to evaluate whether metalloporphyrin models could mimic
      the action of cytochrome P-450 in the oxidation of atrazine, a herbicide. The
      commercially available second-generation metalloporphyrins 5,10,15,20
      tetrakis(2,6-dichlorophenyl)porphyrin metal(III) chloride [M(TDCPP)Cl] and
      5,10,15,20-tetrakis(pentafluorophenyl)porphyrin metal(III) chloride [M(TFPP)Cl]
      (metal = Fe or Mn) and the oxidants iodosylbenzene and metachloroperbenzoic acid
      were employed in this study. Results showed that the metalloporphyrins used here
      can oxidize atrazine. Yields as high as 32% were obtained for the Mn(TFPP)Cl/PhIO
      system, which shows that these catalysts can mimic both the in vivo and the in
      vitro action of cytochrome P-450, with formation of the metabolites DEA and DIA.
      The formation of five other unknown products was also detected, but only one of
      them could be identified, since the other four were present in very low
      concentrations. The compound COA, identified by mass spectrometry, was the main
      product in most of the oxidation reactions.

PMID- 17177536
TI  - Foliar-applied glyphosate substantially reduced uptake and transport of iron and
      manganese in sunflower (Helianthus annuus L.) plants.
AB  - Evidence clearly shows that cationic micronutrients in spray solutions reduce the
      herbicidal effectiveness of glyphosate for weed control due to the formation of
      metal-glyphosate complexes. The formation of these glyphosate-metal complexes in
      plant tissue may also impair micronutrient nutrition of nontarget plants when
      exposed to glyphosate drift or glyphosate residues in soil. In the present study,
      the effects of simulated glyphosate drift on plant growth and uptake,
      translocation, and accumulation (tissue concentration) of iron (Fe), manganese
      (Mn), zinc (Zn), and copper (Cu) were investigated in sunflower (Helianthus
      annuus L.) plants grown in nutrient solution under controlled environmental
      conditions. Glyphosate was sprayed on plant shoots at different rates between
      1.25 and 6.0% of the recommended dosage (i.e., 0.39 and 1.89 mM glyphosate
      isopropylamine salt). Glyphosate applications significantly decreased root and
      shoot dry matter production and chlorophyll concentrations of young leaves and
      shoot tips. The basal parts of the youngest leaves and shoot tips were severely
      chlorotic. These effects became apparent within 48 h after the glyphosate spray.
      Glyphosate also caused substantial decreases in leaf concentration of Fe and Mn
      while the concentration of Zn and Cu was less affected. In short-term uptake
      experiments with radiolabeled Fe (59Fe), Mn (54Mn), and Zn (65Zn), root uptake of
      59Fe and 54Mn was significantly reduced in 12 and 24 h after application of 6% of
      the recommended dosage of glyphosate, respectively. Glyphosate resulted in almost
      complete inhibition of root-to-shoot translocation of 59Fe within 12 h and 54Mn
      within 24 h after application. These results suggest that glyphosate residues or
      drift may result in severe impairments in Fe and Mn nutrition of nontarget
      plants, possibly due to the formation of poorly soluble glyphosate-metal
      complexes in plant tissues and/or rhizosphere interactions.

PMID- 17177537
TI  - Residues and persistence of neem formulations on strawberry after field
      treatment.
AB  - Azadirachtoids were determined by liquid chromatography/mass spectrometry (LC/MS)
      in five methanolic seed extracts of the neem tree and in a commercial
      formulation. On average, seed extracts contain azadirachtin A (10.9%),
      azadirachtin B (3.5%), nimbin (10.4%), and large quantities of salannin (19.0%).
      The composition of the commercial formulations may present different
      azadirachtoids contents depending on the natural extracts used in the
      preparation. Because these compounds may also show insecticide activity, the
      efficacy on field of these formulations may be very different. Photodegradation
      of pure azadirachtoids was also studied. Azadirachtins and related compounds are
      very sensitive to sunlight, degrading rapidly, with half-lives of the order of
      11.3 h for azadirachtin A and 5.5 h for azadirachtin B and few minutes for the
      other limonoids compounds studied. The residues of azadirachtins and the main
      constituents, e.g., salannin, nimbin, deacetylnimbin, and deacetylsalannin, of
      the neem seed extract were determined on strawberries after field treatment using
      two different formulations. This residue study on strawberry was carried out to
      assess not only the azadirachtin content but also the main azadirachtoids
      contents. Three days after field application at five times the dose recommended
      by the manufacturer, residues of azadirachtin A and B were 0.03 and 0.01 mg/kg,
      respectively, while residues of salannin (LOQ 0.01 mg/kg) and nimbin (LOQ 0.5
      mg/kg) were not detectable.

PMID- 17177538
TI  - Aluminum tolerance of two wheat cultivars (Brevor and Atlas66) in relation to
      their rhizosphere pH and organic acids exuded from roots.
AB  - Phytotoxicity of aluminum (Al) has become a serious problem in inhibiting plant
      growth on acid soils. Under Al stress, the changes of rhizosphere pH, root
      elongation, absorption of Al by wheat roots, organic acids exuded from roots, and
      some main factors related to Al-tolerant mechanisms have been studied using
      hydroponics, fluorescence spectrophotometry, and high performance liquid
      chromatography (HPLC). Two wheat cultivars, Brevor and Atlas66, differing in Al
      tolerance are chosen in the study. Accordingly, the rhizosphere pH has a positive
      effect on Al tolerance. Atlas66 (Al-tolerant) has higher capability to maintain
      high rhizosphere pH than Brevor (Al-sensitive) does. High pH can reduce Al3+
      activity and toxicity, and increase the efficiency of exuding organic acids from
      the roots. More inhibition of root elongation has been found in Brevor because of
      the exposure of roots to Al3+ solution at low pH. Brevor accumulate more Al in
      roots than Atlas66 even at higher pH. Al-induced exudation of malic and citric
      acids has been found in Atlas66 roots, while no Al-induced organic acids have
      been found in Brevor. These results indicate that the Al-induced secretion of
      organic acids from Atlas66 roots has a positive correlation with Al tolerance.
      Comprehensive treatment of Al3+ and H+ indicates that wheat is adversely
      influenced by excess Al3+, rather than low pH.

PMID- 17177539
TI  - Variation of wheat root exudates under aluminum stress.
AB  - The wheat (Triticum aestivum L.) cultivar Yangzhou 158 was used as a reference.
      The wheat root exudates were collected using a hydroponic mode. The changes of
      the electrolytes, H+, sugar, organic acids, amino acids, and secondary
      metabolites in wheat root exudates induced by aluminum (Al) were studied. The
      research results show that Al stress affects wheat root exudation. The secreted
      electrolytes and sugar increase with the increasing of the external Al3+
      concentration. The total amount of secreted amino acids has a specific
      correlation with the external Al3+ concentration. At first, the amino acids
      secrete normally, but when Al3+ concentration is over 10 mg.L-1, the amino acid
      constitution varies obviously. Under Al stress, some original secondary
      metabolites disappear gradually, and other new secondary metabolites release
      simultaneously. Increasing the external Al3+ concentration gradually stimulates
      the exudation of organic acids. The organic acid levels in the wheat root zone
      increase in response to Al treatments. Active Al ions are accumulated in wheat
      roots. This Al-dependent variation in wheat root exudates suggests a specific Al
      induced response of the wheat.

PMID- 17177540
TI  - Effects of combined and sequential addition of dual oxidants (H2O2/S2O8(2-)) on
      the aqueous carbofuran photodegradation.
AB  - Carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) (CBF) is a
      widely used insecticide. Traditional methods like hydrolysis and direct
      photolysis cannot remove CBF effectively. In this study, the photodecay of 0.1 mM
      CBF in UV/H2O2, UV/S2O8(2-), and UV/H2O2/S2O8(2-) and sequential addition of a
      second oxidant were studied under UV light at 254 nm. The degradations of CBF
      follow pseudo-first-order decay kinetics. Direct photolysis was slow, but the
      corresponding degradation rate was increased with the addition of hydrogen
      peroxide (H2O2) or potassium peroxydisulfate (K2S2O8). In the UV/H2O2 reaction,
      the optimum reaction rate was 0.9841 min-1 at 10 mM H2O2 (pH 7); however,
      retardation is observed if H2O2 is overdosed. Such retardation is not observed in
      the UV/S2O8(2-) system, but a nonlinear increment of removal efficiency is
      identified. The UV/H2O2/S2O8(2-) process on the other hand shows the best
      performance in CBF degradation, but it has a less effective mineralization than
      that of the sole UV/S2O8(2-) reaction.

PMID- 17177541
TI  - Controlled release of isoproturon, imidacloprid, and cyromazine from alginate
      bentonite-activated carbon formulations.
AB  - Different alginate-based systems of isoproturon, imidacloprid, and cyromazine
      have been investigated in order to obtain controlled release (CR) properties. The
      basic formulation [sodium alginate (1.50%), pesticide (0.30%), and water] was
      modified using different amounts of bentonite and activated carbon. The higher
      values of encapsulation efficiency corresponded to those formulations prepared
      with higher percentages of activated carbon, showing higher encapsulation
      efficiency values for isoproturon and imidacloprid than for cyromazine, which has
      a higher water solubility. The kinetic experiments of imidacloprid/isoproturon
      release in water have shown us that the release rate is higher in imidacloprid
      systems than in those prepared with isoproturon. Moreover, it can be deduced that
      the use of bentonite and/or activated carbon sorbents reduces the release rate of
      the isoproturon and imidacloprid in comparison with the technical product and
      with alginate formulation without modifying agents. The highest decrease in
      release rate corresponds to the formulations prepared with the highest percentage
      of activated carbon. The water uptake, permeability, and time taken for 50% of
      the active ingredient to be released into water, T50, were calculated to compare
      the formulations. On the basis of a parameter of an empirical equation used to
      fit the pesticide release data, the release of isoproturon and imidacloprid from
      the various formulations into water is controlled by a diffusion mechanism. The
      sorption capacity of the sorbents and the permeability of the formulations were
      the most important factors modulating pesticide release. Finally, a linear
      correlation of the T50 values and the content of activated carbon in formulations
      were obtained.

PMID- 17177542
TI  - Modeling evaluation of carbaryl degradation in a continuously stirred tank
      reactor by anodic fenton treatment.
AB  - Anodic Fenton treatment (AFT) has been shown to be effective in removing
      pesticides from aqueous solution in batch reactors with the formation of less
      toxic and more biodegradable products. To facilitate practical application of
      AFT, carbaryl degradation in a continuously stirred tank reactor (CSTR) by AFT
      was investigated under different experimental conditions, such as carbaryl inlet
      concentration, Fenton reagent concentration/ratio, and carbaryl feeding flow
      rate. A higher Fe2+ delivery rate and H2O2 to Fe2+ ratio (H2O2:Fe2+) were found
      to favor the carbaryl degradation process, whereas flow rate was shown to be a
      much less significant factor to influence the degradation rate under the
      evaluated experimental conditions. A kinetic-based semiempirical model was
      developed to simulate the experimental data, and a very good fit between the
      model and the raw data was found (R2 > 0.99). A dimensionless parameter (k/q2)
      was found to be a good indicator of the degradation rate; that is, the higher the
      k/q2value is, the faster the degradation process is. The rate parameter (k) can
      be used to evaluate the degradation rate when the flow rate is invariant for a
      given pesticide. The shape parameter (beta) is most likely related to the
      availability and reactivity of Fenton reagents and hydroxyl radicals. To compare
      the degradation rate of different pesticides, more information other than k/q2,
      k, and beta values, such as the instantaneous degradation rate vs time
      relationship, needs to be considered.

PMID- 17177543
TI  - Responses of soil microorganisms and enzymes to repeated applications of
      chlorothalonil.
AB  - Introduction of anthropogenic chemicals into soil may have lasting effects on
      soil microbial activities and thus soil health. This study was conducted with
      chlorothalonil to evaluate its effects on soil bacterial, fungal, and
      actinomycete populations and soil enzymes (acid phosphatase, alkaline
      phosphatase, urease, catalase, and invertase) after repeated applications. After
      the first addition of chlorothalonil, the soil bacterial and actinomycete
      populations were significantly reduced, whereas the population of soil fungi was
      unchanged. The most marked inhibition on soil microorganisms was observed after
      the second pesticide addition. However, after initial variations, soil bacteria,
      fungi, and actinomycetes adapted gradually to chlorothalonil, and the negative
      effects became transient and weaker following the third and fourth treatments.
      The inhibitory effect of repeated chlorothalonil applications on soil enzymes
      followed a similar trend to that on soil microorganisms. Repeated chlorothalonil
      applications did not result in significant changes in its persistence. Three
      bacterial strains capable of utilizing chlorothalonil as a sole source of carbon
      and energy for growth were isolated 21 days after the fourth treatment with
      chlorothalonil, which indicated that the capability of soil microorganisms for
      degrading chlorothalonil was formed during the experiment.

PMID- 17177544
TI  - Synthesis and structure determination of covalent conjugates formed from the
      sulfury-roasty-smelling 2-furfurylthiol and di- or trihydroxybenzenes and their
      identification in coffee brew.
AB  - Recent investigations demonstrated that the reaction of odor-active thiols such
      as 2-furfurylthiol with thermally generated chlorogenic acid degradation products
      is responsible for the rapid aroma staling of coffee beverages. To get a clear
      understanding of the molecular mechanisms underlying this aroma staling, the
      existence of putative phenol/thiol conjugates needs to be verified in coffee. The
      aim of the present study was therefore to synthesize such conjugates for use as
      reference substances for LC-MS screening of coffee. To achieve this, catechol, 3
      methyl-, 4-methyl-, and 4-ethylcatechol, pyrogallol, hydroxyhydroquinone, 5-O
      caffeoylquinic acid, and caffeic acid, respectively, were reacted with 2
      furfurylthiol in the presence of iron(III) chloride and air oxygen. After
      purification, the structures of 25 phenol/thiol conjugates were identified by
      means of LC-MS/MS and 1D/2D NMR experiments. Using these compounds as reference
      materials, four conjugates, namely, 3-((2-furylmethyl)sulfanyl)catechol, 3-((2
      furylmethyl)sulfanyl)-5-ethylcatechol, 4-((2
      furylmethyl)sulfanyl)hydroxyhydroquinone, and 3,4-bis((2-furylmethyl)sulfanyl)
      hydroxyhydroquinone, were identified for the first time in coffee brew by means
      of HPLC-MS/MS(MRM). These findings clearly demonstrate catechol, 4-ethylcatechol,
      and hydroxyhydroquinone as the primary thiol trapping agents involved in the
      aroma staling of coffee beverages.

PMID- 17177545
TI  - Quantitative precursor studies on di- and trihydroxybenzene formation during
      coffee roasting using "in bean" model experiments and stable isotope dilution
      analysis.
AB  - The objective of this study was to investigate the potential of various raw bean
      components as precursors of pyrogallol (1), hydroxyhydroquinone (2), catechol
      (3), 4-ethylcatechol (4), 4-methylcatechol (5), and 3-methylcatechol (6) under
      quasi "natural" roasting conditions by using the recently developed "in bean"
      model roast experiments. Freeze-dried, fully extracted bean shells were loaded
      with aqueous solutions of either single coffee compounds or fractions isolated
      from the raw bean solubles. After freeze-drying, these reconstituted beans were
      roasted, aqueous coffee brews were prepared, and the target phenols were
      quantified by means of a stable isotope dilution assay with LC-MS/MS detection.
      On the basis of the quantitative data, it can be concluded that upon coffee bean
      roasting, catechol (3) is primarily formed by degradation of caffeoylquinic acids
      from both the caffeic acid and the quinic acid moiety of the molecule, as well as
      from Maillard-type reactions from carbohydrates and amino acids. In contrast,
      pyrogallol (1) and hydroxyhydroquinone (2) are efficiently generated from
      carbohydrates and amino acids and, in addition, from free or chlorogenic acid
      bound quinic acid moieties. 4-Ethylcatechol (4) is exclusively generated upon
      thermal breakdown of caffeic acid moieties. 3-Methylcatechol (6) is formed
      primarily from the Maillard reactions and, to a minor extent, also from various
      phenolic precursors, whereas 4-methylcatechol (5) is produced in trace amounts
      only from all of the different precursors investigated. On the basis of this
      precursor study, reaction routes explaining the formation of the target phenols
      are proposed.

PMID- 17177546
TI  - Comparison of the amounts of volatile compounds in French protected designation
      of origin virgin olive oils.
AB  - Headspace solid-phase microextraction (HS-SPME) -gas chromatography using flame
      ionization detection and multivariate analysis were applied to the study of the
      specificity of protected designation of origin (PDO) virgin olive oils produced
      in a southern French region (Alpes-Maritimes) based on their volatile compounds.
      A total of 35 PDO olive oils from Nice, 6 commercial oils, and 12 other French
      PDO olive oils were analyzed. Recorded data were subjected to principal component
      analysis (PCA) and soft independent modeling of class analogy (SIMCA). The method
      developed here was able to perfectly distinguish different qualities of olive
      oils. Representative samples from each class obtained by chemometric treatment
      were analyzed by HS-SPME and GC-MS. PCA and SIMCA of chromatographic data were
      related to sensory analysis and led to a better understanding of the chemical
      features and observed sensory effects of olive oils.

PMID- 17177547
TI  - Quantitative structure-activity relationship study of bitter peptides.
AB  - A database consisting of 224 di- to tetradecapeptides and five amino acids was
      compiled to study quantitative structure-activity relationships of bitter
      peptides. Partial least-squares regression-1 analysis was conducted using the
      amino acid three z-scores and/or three parameters (total hydrophobicity, residue
      number, and log mass values) as X-variables and bitterness values (log 1/T where
      T is the bitterness threshold) as Y-variables. Using the three parameters only,
      significant models (p < 0.001) were obtained describing the entire data set as
      well as data subsets, except that comprised only of octa- to tetradecapeptides.
      For data sets comprising different peptide lengths, the models were improved by
      including the three z-scores at the N-terminal and C-terminal positions.
      Correlation coefficients for bitterness prediction of 48 dipeptides and 12
      pentapeptides were 0.75 (RMSEP = 0.53) and 0.90 (RMSEP = 0.48), respectively.
      Bulky hydrophobic amino acids at the C terminus and bulky basic amino acids at
      the N terminus were highly correlated to bitterness.

PMID- 17177548
TI  - Isotopic criteria in the characterization of aromatic molecules. 1. Hydrogen
      affiliation in natural benzenoid/phenylpropanoid molecules.
AB  - The site-specific isotope ratios of several families of aromatic molecules are
      analyzed in terms of hydrogen affiliation and discriminating potential. Among the
      aromatic molecules produced by plants, many are biosynthesized by the shikimate
      pathway, but the terpenic pathway also forms some compounds with a benzenic ring.
      In compounds of the phenylpropanoid family, specific hydrogen connections are
      determined with cinnamic acid, a key intermediate in the formation of a large
      number of aromatic molecules. Then affiliations through the phenylalanine
      precursor, back to the parent d-erythrose 4-phosphate and phosphoenolpyruvate
      molecules and finally to glucose, are considered. Typical isotopic profiles of
      the benzenic ring in natural, as compared to non-natural, molecules are defined.
      The dispersion observed in the (D/H)i ratios of the lateral chains is
      illustrative of diverse mechanistic responses and the role of exchange phenomena.
      The isotopic patterns of aromatic molecules pertaining to the terpenic family are
      drastically different from those of the shikimate descendants, and they exhibit
      much less variability. They enable the stereochemical affiliation of individual
      hydrogen atoms to be traced back first to the parent atoms in the common
      intermediate, geranyl diphosphate, then to the glyceraldehyde 3-phosphate and
      pyruvate couple involved in the DOXP pathway, and ultimately to the glucose
      precursor. The results illustrate the aptitude of the site-specific isotope
      ratios not only to authenticate natural with respect to chemical molecules but
      also to characterize different metabolic pathways and to reveal differences
      associated with the nature of the plant precursor.

PMID- 17177549
TI  - Isotopic criteria in the characterization of aromatic molecules. 2. Influence of
      the chemical elaboration process.
AB  - Most valued natural aromatic molecules can be substituted by their low-cost
      chemical counterparts. Isotopic methods, which offer the most powerful tool to
      infer the origin of a molecule, are applied to the characterization of a large
      number of chemical aromatic species. Isotopic affiliation between precursors and
      products is investigated in several types of reactions: oxidation of benzyl
      chloride and benzyl alcohol and hydrolysis of benzylidene chloride and
      cinnamaldehyde. The isotopic parameters strongly depend not only on the type of
      process but, for a given process, on the experimental conditions of the reaction.
      Kinetic isotope effects occurring in several formylation reactions are estimated.
      It is shown that, in the drastic experimental conditions of many industrial
      processes, the benzenic hydrogen atoms may be affected by exchange phenomena.
      Consequently, the site-specific isotopic parameters of the ring fragment of
      chemical species are usually much less stable than those of the corresponding
      natural molecules biosynthesized in mild environments. The isotope ratios of
      substituents such as CH3, CH2Cl, and CHO are more resistant to exchange and
      provide useful criteria for characterizing both the raw materials and the
      process. It is shown in particular that radical hydrogen abstraction in toluene
      to produce benzyl chloride induces relatively moderate fractionation effects. In
      contrast, oxidation reactions frequently produce strong fractionation effects. In
      particular, industrial direct oxidation of toluene into benzaldehyde is
      characterized by deuterium enrichments at the formyl site, which may exceed 900
      ppm. Taking into account the large magnitude and high variability of many
      fractionation effects occurring in chemical reactions, the isotopic fingerprint
      may provide unambiguous criteria, not only for excluding a natural origin and
      characterizing the type of process, but also for differentiating molecules
      synthesized by a given process in different industrial contexts. The isotopic
      fingerprint may therefore be used by manufacturers as a powerful label for
      characterizing their production batches.

PMID- 17177550
TI  - Interactions of the sweet protein brazzein with the sweet taste receptor.
AB  - Brazzein is a small, potently sweet protein. Homology modeling has been used to
      construct a model of the ligand-binding domain of the sweet taste receptor, and
      low-resolution docking has been used to identify potential modes of brazzein
      receptor binding. Published brazzein mutation-taste data were then used to select
      one of these as the most likely brazzein-receptor binding orientation. This
      orientation places brazzein in contact primarily with the T1R2 subunit of the
      receptor, and it accounts for 21 of the 23 mutation results examined.

PMID- 17177551
TI  - Myoglobin oxidation in a model system as affected by nonheme iron and iron
      chelating agents.
AB  - A model system was used to study the effect of nonheme iron on myoglobin
      oxidation at pH 5.6 and pH 7.2 at 23 degrees C. The addition of ferrous iron
      significantly (p < 0.05) increased the rate of myoglobin oxidation in the absence
      of lipid, demonstrating that iron promoted myoglobin oxidation independent of the
      effect of lipid oxidation. The addition of the type II, iron chelating
      antioxidants sodium tripolyphosphate (at pH 7.2) or milk mineral (at pH 5.6)
      negated the effect of added iron, slowing oxidation of myoglobin. A clear
      concentration dependence was seen for iron-stimulated myoglobin oxidation, based
      on both spectral and visual evidence. Further investigation is needed to
      determine the possible role for nonheme ferrous iron on myoglobin oxidation in
      vivo or in meat.

PMID- 17177553
TI  - Pigments in avocado tissue and oil.
AB  - Pigments are important contributors to the appearance and healthful properties of
      both avocado fruits and the oils extracted from these fruits. This study
      determined carotenoid and chlorophyll pigment concentrations in the skin and
      three sections of the flesh (outer dark green, middle pale green, and inner
      yellow flesh-nearest the seed) and anthocyanin concentrations in the skin of Hass
      avocado during ripening at 20 degrees C. Pigments were extracted from frozen
      tissue with acetone and measured using high-performance liquid chromatography.
      Pigments were also measured in the oil extracted from freeze-dried tissue
      sections by an accelerated solvent extraction system using hexane. Carotenoids
      and chlorophylls identified in the skin, flesh, and oil were lutein, alpha
      carotene, beta-carotene, neoxanthin, violaxanthin, zeaxanthin, antheraxanthin,
      chlorophylls a and b, and pheophytins a and b with the highest concentrations of
      all pigments in the skin. Chlorophyllides a and b were identified in the skin and
      flesh tissues only. As the fruit ripened and softened, the skin changed from
      green to purple/black, corresponding to changes in skin hue angle, and a
      concomitant increase in cyanidin 3-O-glucoside and the loss of chlorophyllide a.
      In flesh tissue, chroma and lightness values decreased with ripening, with no
      changes in hue angle. The levels of carotenoids and chlorophylls did not change
      significantly during ripening. As fruit ripened, the total chlorophyll level in
      the oil from the flesh sections remained constant but declined in the oil
      extracted from the skin.

PMID- 17177552
TI  - A novel serine protease cryptolepain from Cryptolepis buchanani: purification and
      biochemical characterization.
AB  - A novel protease is purified to homogeneity from the latex of a medicinally
      important plant Cryptolepis buchanani of family Apocynaceae (formerly
      Asclepiadaceae). The enzyme named cryptolepain has a molecular mass of 50.5 kDa.
      The isoelectric point and extinction coefficient (epsilon280nm1%) are 6.0 and
      26.4, respectively. Cryptolepain contains 15 tryptophans, 41 tyrosines, and eight
      cysteine residues forming four disulfide bridges. The detectable carbohydrate
      moiety in the enzyme was found to be 6-7%. Cryptolepain hydrolyzes denatured
      natural substrates like casein, azocasein, and azoalbumin with high specific
      activity. The protease is exclusively inhibited by serine protease inhibitors
      phenylmethansulfonyl fluoride and diisopropyl fluorophosphate. Hydrolysis of
      azoalbumin by the cryptolepain is optimal in the pH range of 8-10 and
      temperatures of 65-75 degrees C. The enzyme shows high stability against pH (2.5
      11.5), temperature (up to 80 degrees C), and chemical denaturants. The Km value
      of the enzyme was found to be 10 microM with azocasein as the substrate. The N
      terminal sequence of cryptolepain is unique and shows only little homology to
      other known serine proteases, which makes this enzyme an ideal candidate for our
      ongoing biochemical and structure-function investigations of proteases. Easy
      availability of the latex and simple purification procedures make the enzyme a
      good system for exploring the biophysical chemistry of serine proteases as well
      as applications in the food industry.

PMID- 17177554
TI  - Green tea protects cytoskeleton from oxidative injury in cardiomyocytes.
AB  - Cardiac ischemia/reperfusion injury results in oxidative stress and poor
      physiological recovery. Episodes of hypoxia/reoxygenation (H/R) cause some subtle
      functional and structural alterations in sarcolemma, mithocondria, sarcoplasmic
      reticulum, nucleus, as well as cytoskeleton. In this report, by using cultured
      rat cardiomyocytes and laser confocal microscopy we have verified the possibility
      to counteract cytoskeleton alterations induced by H/R with the supplementation of
      an antioxidant agent, a green tea extract (GTE), and compared its effects to
      those of alpha-tocopherol. Moreover the effects of GTE on cell viability and
      cytosolic antioxidant activity have been evaluated. H/R induced myocardial damage
      occurs as histological alterations such as degeneration and disorganization of
      the cytoskeleton and loss of structural integrity of the nucleus. GTE
      supplementation increases cytosolic antioxidant activity and shows protective
      effects on cardiomyocyte cytoarchitecture and viability.

PMID- 17177555
TI  - Stability of acidic egg white protein emulsions containing xanthan gum.
AB  - The influence of xanthan gum concentration on the physicochemical stability of
      model oil-in-water emulsions prepared with egg white protein at pH 3.8 and
      containing 150 mM NaCl was investigated by following droplet aggregate formation,
      rheological changes, and serum separation with storage time. Egg white emulsions
      were more strongly flocculated and exhibited higher stability against creaming
      than those of yolk, irrespective of the presence or absence of xanthan. Depletion
      effects, originating from the presence in the continuous phase of the emulsions
      of nonadsorbing xanthan molecules, intensified droplet-droplet flocculation
      effects and resulted in large droplet flocs. At relatively low xanthan contents,
      the emulsions exhibited higher stability against creaming compared to the
      respective control emulsions probably due to the formation of a continuous
      droplet aggregate network structure. At higher xanthan contents, less extensive
      droplet interactions, due to slowly evolving microstructure of phase-separated
      xanthan-rich and xanthan-depleted regions, resulted in emulsions exhibiting
      increased stability against creaming. The role of interactions between protein
      molecules adsorbed on neighboring droplets in these changes and their effect on
      emulsion aging are discussed.

PMID- 17177556
TI  - Electromigration behavior of a mixture of chitosan oligomers at different
      concentrations.
AB  - In this study, the effect of the concentration of a chitosan oligomer mixture on
      its electrophoretic behavior was studied as a function of pH and ionic strength
      added. It was shown that the concentration has a significant effect on the
      average electrophoretic mobility of the chitosan oligomer mixture and on
      isoelectric point. At a concentration of 3%, the ionic strength added did not
      show any effect on the electromigration behavior of the chitosan oligomer
      mixture. By decreasing the concentration of the chitosan oligomer mixture, ionic
      strength showed a significant effect on the average electrophoretic mobility but
      not on the isoelectric point. The highest shift of the isoelectric point was
      recorded in water at 0.003% concentration of the oligomer mixture. Under these
      conditions, the isoelectric point was at pH 5 whereas it was at pH 8 at 3%
      concentration of chitosan oligomer mixture. Electrophoretic measurements were
      also taken in water/ethanol aqueous medium. By adding ethanol to the medium, the
      average electrophoretic mobility decreased. This would have been caused by the
      increase in viscosity of the medium. Increasing ethanol ratio in the running
      medium, the isoelectric point moved from pH 5 in water up to pH 6-8 dependently
      on chitosan oligomer mixture concentration and ethanol content of the medium.

PMID- 17177557
TI  - Functional lipid characteristics of Turkish Tombul hazelnut (Corylus avellana
      L.).
AB  - The quality of crude oil extracted from Tombul (Round) hazelnut, grown in the
      Giresun province of Turkey, was evaluated for its fatty acid, triacylglycerol
      (TAG), tocol, and phytosterol compositions. Oleic acid contributed 82.78% to the
      total fatty acids, followed by linoleic, palmitic, and stearic acids. Among 12
      TAGs separated, 11 were identified (including one unknown): LLL, OLL, PLL, OOL,
      POL, PPL, OOO, POO, PPO, SOO, and PSO (where P, palmitoyl; S, stearoyl; O,
      oleoyl; and L, linoleoyl). The main components were OOO (71.31%), OOL (12.26%),
      and POO (9.45%), reflecting the high content of oleic acid present in hazelnut
      oil. Seven tocol isoforms (four tocopherols and three tocotrienols) and eight
      phytosterols as well as cholesterol were positively identified and quantified;
      among these, alpha-tocopherol (40.40 mg/100 g) and beta-sitosterol (134.05 mg/100
      g) were predominant in hazelnut oil and contributed 78.74 and 81.28% to the total
      tocols and phytosterols present, respectively. Tocotrienols were detected in
      small amounts (1.02% to the total tocols). The crude hazelnut oil extracted from
      Turkish Tombul hazelnut, thus, serves as a good source of nutrients, bioactives,
      and health-promoting components.

PMID- 17177559
TI  - Regulatory effect of amino acids on the pasting behavior of potato starch is
      attributable to its binding to the starch chain.
AB  - The binding of an amino acid, glycine (Gly), alanine (Ala), epsilon-aminocaproic
      acid (-AC), monosodium glutamate (GluNa), or lysine (Lys), to starch was examined
      by a biomolecular interaction analyzer (IAsys). A starch sample (ATS) hydrolyzed
      to an extent of 1% hydrolysis rate with 15% sulfuric acid was used as a model
      starch for the binding examination. The reducing end of ATS was oxidized by the
      Somogyi reagent, and the conversion of the reducing end to the carboxyl group of
      ATS was confirmed by a carboxylic acid fluorescence labeling reagent. The
      oxidized ATS was immobilized to the amino group of a sensor cuvette by using
      water-soluble carbodiimide and N-hydroxysuccinimide through an amide bond. The
      IAsys examination showed that Gly, Ala, and epsilon-AC scarcely bound to the
      immobilized starch chains but that GluNa and Lys favorably bound with their
      increasing concentrations. The relative binding index (RBI) of each amino acid
      was defined by the ratio of the slope of the linear regression equation between
      the binding response and the concentration for each amino acid to that for Gly.
      Because the relationships between the RBI and the pasting characteristics
      (pasting temperature, peak viscosity, breakdown, and swelling index) could each
      be expressed by a linear regression equation with a high correlation coefficient,
      it is concluded that the regulation of the pasting behavior of starch with an
      amino acid is caused by binding of the amino acid to the starch chains.

PMID- 17177558
TI  - Processing of soybean products by semipurified plant and microbial alpha
      galactosidases.
AB  - Galactooligosaccharides (GO) are responsible for intestinal disturbances
      following ingestion of legume-derived products. Enzymatic reduction of GO level
      in these products is highly desirable to improve their acceptance. For this
      purpose, plant and microbial semipurified alpha-galactosidases were used for GO
      hydrolysis in soybean flour and soy molasses. alpha-Galactosidases from soybean
      germinating seeds, Aspergillus terreus, and Penicillium griseoroseum presented
      maximal activities at pH 4.0-5.0 and 45-65 degrees C. The KM,app values
      determined for raffinose by the soybean, A. terreus, and P. griseoroseum alpha
      galactosidases were 3.44, 19.39, and 20.67 mM, respectively. The enzymes were
      completely inhibited by Ag+ and Hg2+, whereas only soybean enzyme was inhibited
      by galactose. A. terreus alpha-galactosidase was more thermostable than the
      enzymes from the other two sources. This enzyme maintained about 100% of its
      original activity after 3 h at 60 C. The microbial alpha-galactosidases were more
      efficient for reducing GO in soybean flour and soy molasses than soybean enzyme.

PMID- 17177560
TI  - Active photosensitizers in butter detected by fluorescence spectroscopy and
      multivariate curve resolution.
AB  - In this study, fluorescence excitation and emission matrices and multivariate
      curve resolution (PARAFAC) were used to detect and characterize active
      photosensitizers spectrally in butter. Butter samples were packed under high
      (air) and low oxygen (<0.05%) atmospheres and exposed to violet, green, or red
      light. Six photosensitizers were found: riboflavin, protoporphyrin,
      hematoporphyrin, a chlorophyll a-like molecule, and two unidentified
      tetrapyrrols. By estimation of relative concentrations, we could follow how each
      sensitizer was photodegraded as function of wavelength, oxygen level, and time.
      The degradation rate of protoporphyrin, hematoporphyrin, chlorophyll a, and one
      of the tetrapyrrols correlated well (0.83-0.91) with the formation of sensory
      measured oxidation. The results suggest that mainly type I photoreactions were
      responsible for the degradation of photosensitizers in both high and low oxygen
      atmosphere. Type II photoreactions (generation of singlet oxygen) were involved
      in the oxidation of butter stored in air. The study shows that PARAFAC modeling
      of fluorescence landscapes is an excellent tool for studying photooxidation in
      complex systems.

PMID- 17177561
TI  - Physicochemical properties of alginate/polycaprolactone-based films containing
      essential oils.
AB  - Oregano, savory, and cinnamon essential oils (EOs) 1% (w/v) were separately
      incorporated as natural antioxidant agents in alginate/polycaprolactone-based
      films. Films were then treated in 2 or 20% (w/v) CaCl2 solutions in order to
      generate insoluble films. The mechanical properties and the insoluble matter of
      films were determined. Intermolecular interactions between film components and
      alginate cross-linkage were characterized by Fourier transform infrared (FTIR)
      spectroscopy. Surface morphology of the polymer membrane was determined by
      scanning electron microscopy (SEM) analysis. Antiradical properties of films were
      also evaluated following a modified colorimetric method using the N,N-diethyl-p
      phenylenediamine (DPPD) discoloration test. Results showed that films treatment
      with CaCl2 (20%) solution increased the percentage of insoluble matter in films
      but did not enhance their mechanical properties. FTIR analysis showed higher
      interactions in films treated in CaCl2 solutions despite the concentration used
      (2 vs 20%). The SEM observations of films showed a smoother surface with a higher
      density when films were treated in CaCl2 (20%) solution. The DPPD test showed
      that the oregano-based films had the highest antiradical properties.

PMID- 17177562
TI  - Amino acid and protein scavenging of radicals generated by iron/hydroperoxide
      system: an electron spin resonance spin trapping study.
AB  - Reduction of free radicals generated by Fe(II)/cumene-hydroperoxide (CumOOH) by
      amino acids (Gly, Cys, Met, His, and Trp) and proteins (bovine serum albumin
      (BSA), beta-lactoglobulin, and lactoferrin) was followed by electron spin
      resonance spectroscopy using alpha-phenyl-N-tert-butylnitrone (PBN), 2-methyl-2
      nitrosopropane (MNP), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin traps.
      The radical species detected were mostly carbon-centered radicals from CumOOH
      fragmentation (methyl/*H3 and ethyl/*H2CH3), although carbon-centered radicals
      originated from amino acids could be formed in the presence of Cys, Met, His, or
      Trp. All proteins and amino acids, except Cys, were effective at inhibiting
      generation of radicals from the Fe(II)/CumOOH system. Trp was the amino acid with
      the highest antiradical activity, followed by His > Gly approximately Met.
      Lactoferrin was the protein showing the most efficient inhibition of radical
      formation from the Fe(II)/CumOOH system, and BSA and beta-lactoglobulin were not
      significantly different in their antiradical activities. These results suggest
      that proteins with higher inhibitory activity on lipid oxidation promoted by
      transition metal catalytic decomposition of hydroperoxides should be those with
      elevated metal-chelating and radical-scavenging properties as well as low
      concentration and accessibility of reducing groups from amino acids capable of
      activating metals, such as sulfhydryl groups.

PMID- 17177563
TI  - Lipid oxidation in a menhaden oil-in-water emulsion stabilized by sodium
      caseinate cross-linked with transglutaminase.
AB  - Transglutaminase-catalyzed cross-linking of interfacial proteins in oil-in-water
      has been shown to influence physical stability, but little is known about how
      this reaction impacts lipid oxidation. Therefore, this study evaluated the
      influence of transglutaminase-induced interfacial protein cross-linking on the
      oxidative stability of casein-stabilized menhaden oil-in-water emulsions.
      Interfacial casein in menhaden oil-in-water emulsions cross-linked by
      transglutaminase (pH 7.0) produced a cohesive interfacial protein layer that
      could not be removed from the emulsion droplet by Tween 20. Although
      transglutaminase cross-linked the interfacial casein, these emulsions did not
      show increased oxidative stability when compared to untreated emulsions as
      determined by measurement of lipid hydroperoxides and thiobarbituric acid
      reactive substances. These results indicate that increasing the cohesiveness of
      proteins at the interface of oil-in-water emulsions does not inhibit lipid
      oxidation. This could be due to the ability of prooxidative species such as iron
      to diffuse through the cross-linked protein layer where it could promote the
      decomposition of lipid hydroperoxides into free radicals that could oxidize
      unsaturated fatty acids in the emulsion droplet core.

PMID- 17177564
TI  - Differential scanning calorimetry evidence of the enhancement of beta-sitosterol
      absorption across biological membranes mediated by beta-cyclodextrins.
AB  - beta-Sitosterol is a plant sterol that has received much attention because of its
      effectiveness in reducing the absorption of dietary cholesterol, as well as in
      offering protection from cardiovascular diseases and cancer development. Thus,
      the knowledge of the interaction of beta-sitosterol with biological membranes can
      help in understanding its mechanism of action. In the present paper, the
      differential scanning calorimetry technique has been used to study the
      interaction of beta-sitosterol with a biomembrane model constituted by
      dimyristoylphosphatidylcholine multilamellar vesicles. Furthermore, kinetic
      experiments have been carried out to follow the uptake of beta-sitosterol by
      biomembranes and the effect of beta-cyclodextrins on such a process. Our results
      indicate that opportune concentrations of beta-cyclodextrins improve the uptake
      of beta-sitosterol by phospholipid membranes.

PMID- 17177565
TI  - Phenolics of Arbutus unedo L. (Ericaceae) fruits: identification of anthocyanins
      and gallic acid derivatives.
AB  - Arbutus unedo L., the strawberry tree (Ericaceae family), is an evergreen shrub
      or small tree, typical of the Mediterranean fringe and climate. The aim of the
      present study was to evaluate the profile of the phenolic constituents of A.
      unedo fruits. Seven compounds were purified by Sephadex LH-20 column
      chromatography of the MeOH extract followed by HPLC and were characterized as
      arbutin, beta-D-glucogalline, gallic acid 4-O-beta-D-glucopyranoside, 3-O
      galloylquinic acid, 5-O-galloylquinic acid, 3-O-galloylshikimic acid, and 5-O
      galloylshikimic acid, by means of NMR and ESI-MS analyses. Moreover, LC-PDA-MS
      analysis of the red pigment of A. unedo fruits revealed the presence of three
      anthocyanins recognized as cyanidin 3-O-beta-D-galactopyranoside, delphinidin 3-O
      beta-D-glucopyranoside, and cyanidin 3-O-beta-D-arabinopyranoside. These pigments
      were also quantified.

PMID- 17177566
TI  - Properties of the protein and carbohydrate fractions in immature wheat kernels.
AB  - The time course of compositional changes in the polysaccharide and protein
      fractions, and of changes in protein structural properties, was investigated in
      grains of two Italian durum wheat cultivars, Ofanto and Duilio, and the pattern
      of changes was found to be specific to each cultivar. The fructo-oligosaccharide
      content in ripening kernels was different between cultivars, as was the pattern
      of starch accumulation. Evaluation of gluten proteins by Western-blotting using
      broad-specificity anti-gliadin antibodies showed the sudden appearance of
      immunoreactive proteins during ripening. Protein surface hydrophobicity and thiol
      content and accessibility were evaluated in conditions apt at assessing changes
      in protein interaction and/or in aggregative patterns. Proteins in the two
      cultivars showed differences in their surface hydrophobicity and in their content
      of accessible thiols. The simultaneous evaluation of changes in the individual
      components indicates that use of immature grains for the production of functional
      foods will require accurate monitoring of the rapidly evolving biopolymer
      patterns, and careful choice of the cultivar.

PMID- 17177567
TI  - Mechanism of wine lactone formation: demonstration of stereoselective cyclization
      and 1,3-hydride shift.
AB  - The cyclization mechanism of (E)-2,6-dimethyl-6-hydroxyocta-2,7-dienoic acid to
      wine lactone under acidic aqueous conditions was investigated using the two
      stereoselectively deuterium-labeled precursors (2E,6R,7Z)-[8-2H]-2,6-dimethyl-6
      hydroxyocta-2,7-dienoic acid and (2E,7E)-(+/-)-[8-2H]-2,6-dimethyl-6-hydroxyocta
      2,7-dienoic acid. A detailed analysis of the generated wine lactone isomers by
      enantioselective multidimensional gas chromatography (MDGC)/ion trap tandem mass
      spectrometry demonstrates that the formation of wine lactone proceeds via a
      nonenzymatic stereoselective cationic cyclization cascade that includes a 1,3
      hydride shift. Usually, such mechanisms are features of cyclization reactions
      that are catalyzed by terpene cyclases. This nonenzymatic conversion of an
      acyclic precursor to a bicyclic monoterpene under relevant cationic cyclization
      conditions has rarely been observed and confirms recent suggestions that the
      precursor itself can provide the chemical functionality required for specific
      steps in the cyclization cascade.

PMID- 17177568
TI  - Investigations on the promoting effect of ammonium hydrogencarbonate on the
      formation of acrylamide in model systems.
AB  - NH4HCO3 is known to promote acrylamide formation in sweet bakery products. This
      effect was investigated with respect to sugar fragmentation and formation of
      acrylamide from asparagine and sugar fragments in model systems under mild
      conditions. The presence of NH4HCO3 led to increases in acrylamide and alpha
      dicarbonyls from glucose and fructose, respectively. As compared to glucose or
      fructose, sugar fragments such as glyoxal, hydroxyethanal, and glyceraldehyde
      formed much higher amounts of acrylamide in reaction with asparagine. The
      enhancing effect of NH4HCO3 is explained by (1) the action of NH3 as base in the
      retro-aldol reactions leading to sugar fragments, (2) facilitated retro-aldol
      type reactions of imines in their protonated forms leading to sugar fragments,
      and (3) oxidation of the enaminols whereby glyoxal and other reactive sugar
      fragments are formed. These alpha-dicarbonyl and alpha-hydroxy carbonyl compounds
      may play a key role in acrylamide formation, especially under mild conditions.

PMID- 17177569
TI  - Cytochrome P450 1A1 expression and activity in Caco-2 cells: modulation by apple
      juice extract and certain apple polyphenols.
AB  - Cytochrome P450 (CYP) 1A1 plays a role in drug metabolism of intestinal cells
      (e.g., by activating certain chemical carcinogens such as polycyclic aromatic
      hydrocarbons into carcinogenic metabolites). In the human colon carcinoma cell
      line Caco-2, we investigated the effects of a defined polyphenolic apple juice
      extract (AJE), the major principle flavonoid/dihydrochalkone constituents
      quercetin and phloretin, and the corresponding prototype glycosides rutin and
      phlorizin on CYP1A1 expression and activity. Incubations were carried out with or
      without the potent aryl hydrocarbon receptor agonist/CYP1A1 inducer 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). AJE and quercetin acted as weak inducers of
      CYP1A1 mRNA and protein, and AJE, quercetin, and phlorizin led to a slight
      induction of CYP1A1-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity.
      However, AJE, quercetin, and phloretin were highly effective in suppressing
      CYP1A1 induction in co-incubations of the cells with 1 nM TCDD. The antagonistic
      effects were seen on the levels of mRNA, enzyme protein, and catalytic activity.
      In contrast, the related glycosides rutin and phlorizin were inactive as inducers
      or inhibitors. Inhibition of CYP1A1 induction was not related to general
      cytotoxicity, which could be completely abolished by the addition of ascorbic
      acid/alpha-tocopherol. AJE, quercetin, and phloretin also antagonized the TCDD
      mediated induction of a reporter gene driven by a regulatory sequence of the
      human CYP1A1 gene promoter. Our findings suggest that apple juice extract can
      antagonize TCDD-mediated CYP1A1 induction by interfering with AhR-dependent gene
      transcription and by inhibiting the catalytic activity of CYP1A1. These effects
      may result in reduced metabolic activation of certain chemical carcinogens, in
      particular, under conditions of sustained AhR activation.

PMID- 17177570
TI  - Physiological effects of extraction juices from apple, grape, and red beet
      pomaces in rats.
AB  - In comparison to classical fruit juice processing, polyphenols and dietary fiber
      can be extracted from pomace by means of pectinases and cellulases. In the
      present study, rats were fed with such produced extraction juices from apples,
      grapes, and red beets as drinking fluids instead of water for 4 weeks to evaluate
      their physiological effects. In all test groups, the intake of extraction juices
      was greater as compared to control (water intake), resulting in a higher urine
      excretion. In the apple and grape group, pH values in feces was lower than
      control. Administration of extraction juices from apples increased fecal counts
      of Lactobacillus and Bifidobacterium. More acetate and total short-chain fatty
      acids appeared in intestinal contents of the apple and red beet group.
      Furthermore, the intestinal contents of test groups contained higher
      concentrations of primary bile acids, cholesterol, and cholesterol metabolites
      but lower concentrations of secondary bile acids. The total amount of steroids
      excreted by these groups was also greater than control. Quercetin and
      isorhamnetin appeared in urine of rats fed extraction juices from apples and
      grapes; in urine of the former group, phloretin was found also. Administration of
      the extraction juices, enriched in secondary plant metabolites and dietary fiber,
      resulted in beneficial nutritional effects in rats.

PMID- 17177571
TI  - Biosynthesis enhancement and antioxidant and anti-inflammatory activities of
      peanut (Arachis hypogaea L.) arachidin-1, arachidin-3, and
      isopentadienylresveratrol.
AB  - Peanut is a potent plant to be induced to synthesize bioactive stilbenoids.
      Bioactivities of those stilbenoids except resveratrol have been meagerly
      investigated. When peanut kernels (Tainan 14, a Spanish cultivar) were imbibed,
      incubated 3 days for germination, sliced, incubated with artificial aeration,
      periodically sampled, lyophilized, extracted with methanol, and subjected to
      reverse-phase HPLC analysis, four major fractionations were detected and
      identified as trans-resveratrol (Res), trans-arachidin-1 (Ara-1), trans-arachidin
      3 (Ara-3), and trans-isopentadienylresveratrol (IPD). During incubation of the
      peanut slices, contents of Res, Ara-1, and Ara-3 increased tremendously from
      initially trace or not detectable amounts up to 147.3, 495.7, and 2414.8
      microg/g, corresponding to 20, 16, and 24 h of incubation, while IPD contents
      continued to increase up to 28 h (4474.4 microg/g). When the four stilbenoids and
      butylated hydroxytoluene (BHT) were subjected to antioxidant characterization by
      various measures, all have exhibited varied potencies of antioxidant activity. In
      particular, retardation of absorbance increase at 234 nm as formation of the
      conjugated diene hydroperoxides in a real pork oil system stored at 60 degrees C,
      supplement of Ara-1 at 100 microM has shown equivalent or even greater activity
      than did BHT. When the media were supplemented with Res, Ara-1, Ara-3, and IPD at
      15 microM for cultivation of mouse macrophage RAW 264.7 cells activated by
      lipopolysaccharide (LPS), the LPS-induced extracellular production of
      prostaglandin E2 (PGE2) and nitric oxide (NO) was significantly inhibited by Ara
      1 (p < 0.001), Res (p < 0.001), Ara-3 (p < 0.01), and IPD (p < 0.01). It is
      noteworthy and of merit that all test stilbenoids have exhibited potent
      antioxidant and anti-inflammatory activities and varied as affected by number of
      hydroxyl groups and isopentenyl or isopentadienyl moiety. KEYWORDS: Arachis
      hypogaea L.; peanut; groundnut; resveratrol; stilbenoids; arachidin; antioxidant;
      anti-inflammation.

PMID- 17177572
TI  - Protection of lipids from oxidation by epicatechin, trans-resveratrol, and gallic
      and caffeic acids in intestinal model systems.
AB  - Consumption of polyphenols is associated with health promotion through diet,
      although many are poorly absorbed in animals and humans alike. Lipid peroxides
      may reach the intestine and initiate deleterious oxidation. Here we measured
      inhibition of the oxidation of linoleic acid (LA) in authentic fluid from rat
      small intestine (RIF) by two dietary polyphenols, a flavonoid, epicatechin (EC),
      and a stilbene, resveratrol (RV), and by gallic (GA) and caffeic (CA) acids, and
      their partition coefficients. Both polyphenols inhibited 80%, and CA inhibited
      65%, of the production of hexanal. GA was the weakest antioxidant in this assay.
      Interestingly, measuring peroxides production in RIF showed that only epicatechin
      inhibited the first stage of oxidation. The oxidizing agent, the antioxidant
      comound, the solution pH and lipophilicity are known to affect the total
      antioxidative activity. We suggest that the mechanism of this activity changes in
      accord with the environment: i.e., RV may act as a free radial scavenger, but
      here, in protecting lipids in intestinal fluid from oxidation, it acts as a
      hydrogen atom donor. Since the concentration of phenolics is much higher in the
      intestinal fluid than is ever achieved in plasma or other body tissues, it is
      suggested that their antioxidant activity could be exerted in the
      gastrointestinal tract (GIT), breaking the propagation of lipid peroxides
      oxidation and production of toxic compounds.

PMID- 17177573
TI  - Experimental study on the removal of dioxins and coplanar polychlorinated
      biphenyls (PCBS) from fish oil.
AB  - Recently, it has been found that fish oils contain a high proportion of
      contaminants, namely, polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated
      dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (cPCBs). In this
      study, the removal of contaminants from fish oil by supercritical CO2 extraction
      (SCE) and by using adsorbents (0.13 wt % of oil) was investigated. Dioxins and
      cPCBs were extracted from fish oil by SCE at a temperature of 60 degrees C and a
      pressure of 28 MPa, and the removal efficiencies for PCDDs and PCDFs were in the
      range of 15-90% and those for cPCBs were in the range of 70-90%. However, 40% of
      the oil was extracted simultaneously with contaminants. On the adsorbent
      treatment, activated carbon showed high efficiency, and the removal efficiencies
      were >90% for PCDDs and PCDFs, but below 30% for cPCBs. A combination of both of
      these methods is more effective, and almost 100% of the total toxicity
      equivalence quantity value could be reduced.

PMID- 17177574
TI  - Determination of spore inactivation during thermal and pressure-assisted thermal
      processing using FT-IR spectroscopy.
AB  - The efficacy of microbial inactivation techniques is currently tested using time
      consuming and labor-intensive plate count methods, which are the principal rate
      limiting steps in developing inactivation kinetic parameters for alternative food
      processing technologies. Fourier transform infrared (FT-IR) spectroscopy combined
      with multivariate analysis was used to quantify viable spores and identify some
      biochemical changes in samples treated by autoclaving, pressure-assisted thermal
      processing (PATP), and thermal processing (TP). Spore suspensions ( approximately
      109 CFU/mL) of Bacillus amyloliquefaciens TMW 2.479 Fad 82, B. amyloliquefaciens
      TMW 2.482 Fad 11/2, B. sphaericus NZ 14, B. amyloliquefaciens ATCC 49764, and
      Clostridium tyrobutyricum ATCC 25755 were treated by PATP (121 degrees C and 700
      MPa) for 0, 10, 20, and 30 s and by TP (121 degrees C) for 0, 10, 20, and 30 s.
      The concentrations of spores in treated samples were determined by plating
      (reference method). Models developed using partial least-squares regression
      (PLSR) for predicting spore levels in treated samples had correlation
      coefficients (r) of >0.99 and standard errors of cross-validation ranging between
      100.2 and 100.5 CFU/mL. Changes in dipicolinic acid (DPA) and secondary structure
      of proteins were found to occur during inactivation of spores by PATP and TP. FT
      IR spectroscopy could rapidly estimate viable bacterial spore levels in PATP- and
      TP-treated spore suspensions, providing an accurate analytical tool for
      monitoring the efficacy of sterilization techniques in inactivating spore-forming
      microorganisms.

PMID- 17177575
TI  - Disposition and metabolic profiling of bisphenol F in pregnant and nonpregnant
      rats.
AB  - The distribution of bisphenol F (4,4'-dihydroxydiphenyl-methane, BPF) was studied
      in female Sprague-Dawley rats. Pregnant and nonpregnant animals were gavaged with
      a single dose of 7 or 100 mg/kg [3H]BPF and were kept for 96 h in metabolic
      cages. The excretion of BPF residues occurred mainly in urine (43-54% of the
      administered dose), which was found to contain at least six different
      metabolites, and to a lesser extent in feces (15-20% of the administered dose).
      Sulfatase treatment and subsequent high-performance liquid chromatography
      analyses suggest that the major urinary metabolite (more than 50% of the
      radioactivity present in urine) is a sulfate conjugate of BPF. At 96 h, BPF
      residues were detectable in all tissues examined with the largest amounts in the
      liver (0.5% of the dose). In pregnant rats dosed at day 17 of gestation, BPF
      residues were detected in the uterus, placenta, amniotic fluid, and fetuses (0.9
      1.3% of the administered dose). Large amounts of radioactivity (8-10% of the
      dose) were still located in the digestive tract lumen at the end of the study.
      After administration of a single oral dose of [3H]BPF, 46% of the distributed
      radioactivity was excreted in bile over a 6 h period. In rats, BPF and/or its
      metabolites very likely undergo enterohepatic cycling, which could be responsible
      for the relatively high amounts of residues still excreted 4 days after BPF
      administration. This bisphenol is efficiently absorbed and distributed to the
      reproductive tract in female rats, and its residues pass the placental barrier at
      a late stage of gestation in rats.

PMID- 17177576
TI  - Aripiprazole in the treatment of schizophrenia: a consensus report produced by
      schizophrenia experts in Italy.
AB  - Schizophrenia is generally a chronic and disabling mental illness.
      Pharmacological therapy, which is used for relief of acute psychotic episodes and
      prevention of subsequent relapse, is essential for the effective management of
      schizophrenia. In order to alleviate the positive symptoms of schizophrenia, all
      antipsychotic agents act on the dopaminergic system. However, strong, high
      affinity dopamine D(2)-receptor blockade may also be responsible for debilitating
      extrapyramidal symptoms (EPS) and hyperprolactinaemia. Unlike conventional
      antipsychotic agents, atypical antipsychotics also exert activity at other
      receptors, and it is generally acknowledged that, compared with conventional
      antipsychotics, atypical agents are associated with a broader spectrum of
      clinical efficacy and are better tolerated. However, other adverse effects such
      as weight gain and metabolic changes are cause for concern with some atypical
      antipsychotics. The novel atypical antipsychotic agent aripiprazole is a partial
      agonist at D(2) receptors that has been shown in clinical trials to be effective
      in treating both the positive and the negative symptoms of schizophrenia, and to
      be well tolerated, with a low propensity for EPS and no clinically significant
      weight gain, hyperprolactinaemia or corrected QT-interval prolongation.
      Aripiprazole thus provides clinicians with another treatment option, and in
      October 2005, schizophrenia experts participated in an expert consensus meeting
      that aimed to agree on a set of guidelines for best-practice use of aripiprazole
      in the acute and long-term management of schizophrenia in Italy. This report
      describes the outcome of the meeting. Our recommendations for dosage and
      administration of aripiprazole are in agreement with the manufacturer's
      prescribing information. Ideally, optimal dosing should be evaluated on an
      individual basis, taking into account patients' characteristics such as the
      presence or absence of agitation. Overall, in our experience, aripiprazole is
      generally a well accepted, well tolerated, safe and broadly effective first-line
      antipsychotic agent. Switching to aripiprazole from maintenance therapy with
      another antipsychotic also works well, provided the change is made gradually,
      involving tapering of the original medication.

PMID- 17177577
TI  - Irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is a disease of unclear, complex pathophysiology
      characterised by abdominal pain and discomfort and altered bowel activity. It
      affects an estimated 10-15% of individuals worldwide and has a large impact on
      quality of life (QOL) and both direct and indirect healthcare costs. Symptoms of
      IBS are usually triggered by disruption of gastrointestinal (GI) function
      secondary to infection, dietary factors, lifestyle changes or psychological
      stress. While most currently available pharmacological treatments of IBS focus on
      symptomatic treatment of the syndrome, agents that attempt to address the
      pathophysiology of the disease, in particular the role of serotonin, have
      received much attention in recent years. However, there is growing concern that
      serotonergic agents as a class may be associated with rare, but serious, episodes
      of ischaemic colitis, with several cases of this complication having been
      reported in association with use of serotonergic agents that have reached the
      market. Thus, there remains an important need for safe and effective agents that
      treat the symptoms of IBS. Otilonium bromide, a spasmolytic agent, has been
      widely used worldwide and has been found to be effective and safe for managing
      abdominal pain. Clinical trials indicate that it improves baseline abdominal pain
      and distension, and is particularly effective in reducing diarrhoea. Combining
      otilonium bromide with benzodiazepines, such as diazepam, may improve the
      efficacy of the agent with respect to GI symptoms, while also treating underlying
      anxiety disorders. More research is required to confirm the efficacy and
      mechanisms of action associated with this combination therapy in IBS. Safety data
      from clinical trials and postmarketing sources indicate that otilonium bromide is
      well tolerated, with a safety profile comparable to placebo in clinical trials
      and only two reported cases of adverse reactions (urticaria) among 10-year
      postmarketing data. This article reviews the pathophysiology and treatment of IBS
      with a particular focus on the role of otilonium bromide in the management of
      this condition.

PMID- 17177578
TI  - Cross-study analysis of the relative efficacies of oral antiviral therapies for
      chronic hepatitis B infection in nucleoside-naive patients.
AB  - BACKGROUND AND OBJECTIVE: Lamivudine and adefovir were approved for treatment of
      chronic hepatitis B virus (HBV) infection based on placebo-controlled trials, and
      entecavir was recently approved on the basis of its superiority over lamivudine
      in phase II/III trials; however, to date, these three therapies have not been
      compared head to head. METHODS: To evaluate the relative efficacy of these
      therapies, we applied a predefined protocol of established statistical techniques
      to compare data from phase III entecavir trials with published clinical trial
      results with lamivudine, adefovir and placebo in nucleoside-naive hepatitis B e
      antigen (HBeAg)-positive and -negative populations. RESULTS: A comprehensive
      literature search identified 612 publications/data sources, of which 28 satisfied
      predefined inclusion criteria. Independent reviewers extracted week 48-52
      histological, virological, biochemical and serological endpoints from these
      sources, which were analysed with a fixed-effects model. For each of the three
      histological endpoints in HBeAg-positive patients (Histological Improvement,
      Ranked Assessment of Necroinflammation [RA-N] and Ranked Assessment of Fibrosis
      [RA-F]), entecavir was superior to adefovir. Entecavir was superior to lamivudine
      for Histological Improvement and comparable to lamivudine for RA-N and RA-F. With
      respect to reducing HBV DNA levels, entecavir (-6.98 log(10) copies/mL) was more
      effective than lamivudine (-5.46 log(10) copies/mL, p < 0.0001) and adefovir (
      3.60 log(10) copies/mL, p < 0.0001), and lamivudine was more effective than
      adefovir (p < 0.0001). The parallel goals of HBV DNA reduction below the limit of
      quantitation (LOQ) [by polymerase chain reaction] and ALT normalisation were
      achieved more often with entecavir (69% and 67% of patients, respectively) than
      with lamivudine (38% and 59%, respectively; p < 0.0001 and p < 0.05,
      respectively) or adefovir (21% and 48%, respectively; both p < 0.0001), and more
      often with lamivudine than with adefovir (p < 0.0001 and p < 0.05, respectively).
      HBeAg seroconversion rates were higher with entecavir (21% of patients) and
      lamivudine (18%) than with adefovir (12%, p < 0.01 and p < 0.05, respectively).
      For each of the three histological endpoints in the HBeAg-negative population,
      entecavir was comparable to adefovir. Entecavir was superior to lamivudine for
      Histological Improvement, and comparable to lamivudine for RA-N and RA-F, and all
      three antivirals were superior to placebo. Entecavir proved superior to
      lamivudine and adefovir in lowering HBV DNA levels (-5.20 vs -4.66 vs -3.91
      log(10) copies/mL, respectively; p < 0.0005 and p < 0.0001, respectively) and in
      suppressing HBV DNA below the LOQ (91% vs 73% vs 51% of patients, respectively;
      both p < 0.0001); in the latter respect, lamivudine was in turn superior to
      adefovir (p < 0.0001). Entecavir was also superior to lamivudine in normalising
      ALT (76% vs 69% patients, respectively; p < 0.05). CONCLUSIONS: Over a 12-month
      treatment period, this analysis predicts that the antiviral efficacy of entecavir
      would be superior to that of lamivudine, which in turn would be superior to that
      of adefovir, in nucleoside-naive patients with chronic HBV infection.

PMID- 17177580
TI  - Effectiveness and satisfaction with zolmitriptan 5 mg nasal spray for treatment
      of migraine in real-life practice: results of a postmarketing surveillance study.
AB  - OBJECTIVE: Addressing the needs of migraineurs by actively seeking patient
      feedback on disease-related disability and treatment satisfaction may lead to
      improved management and treatment outcomes. Patient feedback can be collected in
      postmarketing surveillance (PMS) studies. The objective of this PMS study was to
      evaluate the efficacy and tolerability of zolmitriptan 5 mg nasal spray in the
      acute treatment of migraine attacks. PATIENTS AND METHODS: Patients received
      zolmitriptan 5 mg nasal spray to treat migraine attacks of any severity and were
      followed up after a maximum of 4 months. Patients evaluated the efficacy and
      tolerability of zolmitriptan nasal spray, and were asked whether they wished to
      continue using zolmitriptan nasal spray and their preference compared with
      previous treatments. Physicians also assessed the efficacy and tolerability of
      zolmitriptan nasal spray. RESULTS: A total of 1838 patients (84.8% females)
      participated in the study. Within 30 minutes of administration of zolmitriptan
      nasal spray, 85.0% of patients reported improvements in headache pain, with 25.1%
      reporting an improvement within 10 minutes. At 1 hour post-dose, 57.9% of
      patients were pain free and 61.7% were able to resume usual daily activities.
      Most patients (72.9%) rated zolmitriptan nasal spray as 'better' than previous
      therapy. The majority (88.8%) expressed a wish to continue using zolmitriptan
      nasal spray. Physicians evaluated the efficacy of zolmitriptan nasal spray as
      'excellent' or 'good' in 89.4% of patients. Tolerability was evaluated as
      'excellent' or 'good' in 91.6% of patients. CONCLUSIONS: Zolmitriptan 5 mg nasal
      spray provides favourable efficacy and tolerability in the acute treatment of
      migraine attacks. Most patients assessed zolmitriptan nasal spray as 'better'
      than previous treatment, with nearly all wishing to continue using it.

PMID- 17177579
TI  - Pilot study of the efficacy and safety of a modified-release magnesium 250 mg
      tablet (Sincromag) for the treatment of premenstrual syndrome.
AB  - BACKGROUND: Magnesium deficiency has been implicated as a possible contributing
      factor to some symptoms of premenstrual syndrome (PMS) and several studies have
      reported a lower intracellular magnesium concentration in women with PMS. Thus,
      it has been suggested that magnesium supplementation may improve certain symptoms
      in women with PMS. OBJECTIVE: This open-label study assessed the efficacy and
      safety of a patented modified-release magnesium 250 mg tablet for improving
      symptoms in women affected by PMS. METHODS: After a 3-month observational period,
      women aged 18-45 years with a regular menstrual cycle (from 25-35 days) who were
      affected by PMS (determined by a score of > or =25 points on a PMS questionnaire)
      [n = 41] were given the modified-release magnesium tablet over three menstrual
      cycles, beginning 20 days after the start of their last menstrual period and
      continuing until the start of their next menstrual period. RESULTS: PMS symptoms
      improved during magnesium treatment. After 3 months, the mean total PMS score
      (primary endpoint), as assessed by the investigator using Moos' Modified
      Menstrual Distress Questionnaire, was significantly lower than before therapy (p
      < 0.0001). During the same period, the mean PMS scores, as recorded in patients'
      diaries (secondary efficacy variables), also showed significant improvements (p <
      0.0001 for all subscales). The relative decreases in total PMS scores, as
      assessed by investigator and patient, were 35.1% and 33.5%, respectively. The
      magnesium tablet was well tolerated, with vertigo the only treatment-related
      adverse event reported (one patient). CONCLUSIONS: We concluded that modified
      release magnesium was effective in reducing premenstrual symptoms in women with
      PMS in this preliminary study.

PMID- 17177589
TI  - Managing "real" anesthesia emergencies on human simulators.

PMID- 17177581
TI  - Cost effectiveness of lopinavir/ritonavir compared with atazanavir in
      antiretroviral-naive patients: modelling the combined effects of HIV and heart
      disease.
AB  - BACKGROUND AND OBJECTIVE: The choice of initial highly active antiretroviral
      therapy (HAART) should take into account the need to balance efficacy, adverse
      event risk, resistance concerns for the treatment of HIV and treatment costs.
      Increased risk of coronary heart disease (CHD) may be of special concern in the
      selection of HAART therapy, because differences in potential CHD risk have been
      reported for different regimens. This study aimed to estimate the long-term
      combined effects of HIV disease and antiretroviral (ARV)-related risk for CHD on
      quality-adjusted survival and healthcare costs for ARV-naive patients. METHODS: A
      previously validated Markov model was updated and supplemented with the
      Framingham CHD risk equation. In the model, the average patient was male, aged 37
      years and had a baseline 10-year CHD risk of 4.6%. Patients started with either
      lopinavir/ritonavir or unboosted atazanavir as the first protease inhibitor (PI).
      Clinical trial data were used to estimate the differences between these two
      therapies. The daily PI costs were $US18.52 for lopinavir/ritonavir and $US22.08
      for atazanavir. Other costs were estimated from Medicaid billing databases and
      average wholesale drug price reports. All model costs were reported as the 2004
      present value in US currency. The model's time horizon reflected a patient's
      lifetime, and the perspective of the analysis was that of the healthcare system
      and did not include indirect costs in the model cost estimates. Various CHD risk
      levels were tested in the sensitivity analysis. RESULTS: In the base case, the
      model predicted a median duration of initial PI regimen of 5.6 years for
      lopinavir/ritonavir and 3.8 years for atazanavir. Over 10 years, patients who
      started on atazanavir had 30 additional AIDS events per 100 patients. Only 0.7
      additional CHD events per 100 patients occurred for those who started on
      lopinavir/ritonavir. The model estimated 10-year total healthcare cost savings of
      $US12,543 per patient in the lopinavir/ritonavir group. The lifetime incremental
      cost effectiveness of lopinavir/ritonavir versus atazanavir was $US6797 per
      quality-adjusted life-year gained. CONCLUSION: Lopinavir/ritonavir is a highly
      cost-effective regimen relative to atazanavir for the treatment of HIV. The
      effect of lopinavir/ritonavir on long-term CHD risk was minimal compared with the
      increased risk of AIDS/death projected for a less efficacious first PI regimen.
      The cost of lipid-lowering drugs and treatment of CHD for patients taking the
      lopinavir/ritonavir regimen was only 1.2% of the cost of AIDS care per person,
      which was too small to have a significant effect on the overall cost savings with
      lopinavir/ritonavir therapy. Thus, a decision to forgo potency and durability in
      an ARV regimen for an ARV-naive patient in favour of a less potent regimen with
      an improved lipid profile may prove to be costly over time, in terms of both
      budget impact and life expectancy.

PMID- 17177582
TI  - Tramadol in the treatment of neuropathic cancer pain: a double-blind, placebo
      controlled study.
AB  - OBJECTIVE: To assess the efficacy, safety and impact on quality of life of
      tramadol in the treatment of neuropathic pain in patients with cancer. METHODS:
      Patients with similar characteristics were grouped in pairs and randomised to
      receive either tramadol or placebo. The initial tramadol dosage was 1 mg/kg every
      6 hours, increasing to 1.5 mg/kg every 6 hours if necessary to control pain.
      RESULTS: The study enrolled 36 patients (22 women, 14 men), with a mean age of 50
      years. In the group receiving tramadol (n = 18), major improvements in pain
      intensity and Karnofsky scores occurred (p < 0.001), sleep quality improved by
      day 45 (p < 0.05) activities of daily living improved (p < 0.05), and use of
      analgesics that had been taken before the study was reduced (p < 0.05) compared
      with the placebo group. There was no difference between the groups with regard to
      changes in the Zung Depression Scale, Beck Anxiety Inventory scores and
      neurophysiological assessments. More patients in the tramadol group experienced
      adverse events (p < 0.05). The most common adverse events were nausea, vomiting
      and constipation. CONCLUSIONS: Tramadol is a therapeutic option for the control
      of neuropathic pain in patients with cancer, and appears to improve quality of
      life in these patients. The analgesic effect of tramadol is independent of
      changes in anxiety, depression and nervous system function.

PMID- 17177590
TI  - Cardiovascular effects of felypressin.
AB  - Cardiovascular effects of felypressin (FEL) were studied in Wistar rats. Heart
      rate and mean arterial pressure measurements were taken in awake rats treated
      with vasopressin (AVP), FEL, or epinephrine (EPI). Each group received either an
      intravenous (IV) or an intracerebroventricular V1 receptor antagonist, saline,
      area postrema removal, or sham surgery. Analysis of variance and Student-Newman
      Keuls (P < .05) were applied. Felypressin and AVP induced a pressor effect, and
      bradycardia was inhibited by IV V1 antagonist. Intracerebroventricular V1
      antagonist and area postrema removal enhanced their pressor effects. Epinephrine
      induced a higher pressor effect and a similar bradycardia that was not affected
      by the treatments. It was concluded that FEL depends on V1 receptors to induce
      pressor and bradycardic effects, and that it produces a high relationship between
      bradycardia and mean arterial pressure variation depending on area postrema and
      central V1 receptors. These effects are potentially less harmful to the
      cardiovascular system than the effects of EPI.

PMID- 17177591
TI  - The effects of a 2-stage injection technique on inferior alveolar nerve block
      injection pain.
AB  - The purpose of this prospective, randomized, single-blinded, crossover study was
      to compare the pain of a traditional 1-stage inferior alveolar nerve (IAN) block
      injection to a 2-stage IAN block technique. Using a crossover design, 51 subjects
      randomly received, in a single-blinded manner, either the traditional IAN block
      or the 2-stage IAN block in 2 appointments spaced at least 1 week apart. For the
      2-stage injection, the needle was inserted submucosally and 0.4 mL of 2%
      lidocaine with epinephrine was slowly given over 1 minute. After 5 minutes, the
      needle was reinserted and advanced to the target site (needle placement), and 1.8
      mL of 2% lidocaine with epinephrine was deposited. For the traditional IAN block,
      following needle penetration, the needle was advanced while depositing 0.4 mL of
      2% lidocaine with epinephrine (needle placement) and then 1.8 mL of 2% lidocaine
      with epinephrine was deposited at the target site. A Heft-Parker visual analogue
      scale was used to measure the pain of needle insertion, needle placement, and
      anesthetic solution deposition. There were no significant differences, as
      analyzed by Wilcoxon matched-pairs signed-ranks test, between needle insertion
      and solution deposition for the 2 techniques in men or women. However, there was
      significantly less pain with the 2-stage injection for needle placement in women.
      In conclusion, the 2-stage injection significantly reduced the pain of needle
      placement for women when compared to the traditional IAN technique.

PMID- 17177593
TI  - Drug therapy in dental practice: general principles. Part 1 - Pharmacokinetic
      considerations.
AB  - The fundamental principles that govern drug therapy are often overlooked by the
      busy clinician. This disregard frequently results in the use of particular drugs
      and regimens that may be less than ideal for the clinical situation being
      managed. By convention, these principles are categorized as pharmacokinetic and
      pharmacodynamic. Pharmacokinetic processes include drug absorption, distribution,
      biotransformation (metabolism), and elimination, essentially reflecting the
      influence of the body on the drug administered. Pharmacodynamics deals with the
      actual mechanisms of action and the effects a drug produces on the patient. This
      latter topic will be addressed in a future continuing education article.

PMID- 17177594
TI  - Visual loss in postconflict southern Sudan.

PMID- 17177592
TI  - Anesthetic efficacy of lidocaine/meperidine for inferior alveolar nerve blocks.
AB  - The authors, using a crossover design, randomly administered, in a single-blind
      manner, inferior alveolar nerve blocks using 36 mg of lidocaine with 18 microg of
      epinephrine or a combination of 36 mg of lidocaine with 18 microg epinephrine
      plus 36 mg meperidine with 18 microg of epinephrine, at 2 separate appointments,
      to 52 subjects. An electric pulp tester was used to test for anesthesia, in 4
      minute cycles for 60 minutes, of the molars, premolars, and central and lateral
      incisors. Anesthesia was considered successful when 2 consecutive 80 readings
      were obtained within 15 minutes and the 80 reading was continuously sustained for
      60 minutes. Using the lidocaine solution, successful pulpal anesthesia ranged
      from 8 to 58% from the central incisor to the second molar. Using the
      lidocaine/meperidine solution, successful pulpal anesthesia ranged from 0 to 17%.
      There was a significant difference (P < .05) between the lidocaine and
      lidocaine/meperidine solutions for the lateral incisors through the second
      molars. We conclude that the addition of meperidine to a standard lidocaine
      solution does not increase the success of the inferior alveolar nerve block.

PMID- 17177595
TI  - Blindness in Sudan: is it time to scrutinise survey methods?

PMID- 17177596
TI  - Prevalence and causes of blindness and low vision in southern Sudan.
AB  - BACKGROUND: Blindness and low vision are thought to be common in southern Sudan.
      However, the magnitude and geographical distribution are largely unknown. We
      aimed to estimate the prevalence of blindness and low vision, identify the main
      causes of blindness and low vision, and estimate targets for blindness prevention
      programs in Mankien payam (district), southern Sudan. METHODS AND FINDINGS: A
      cross-sectional survey of the population aged 5 y and above was conducted in May
      2005 using a two-stage cluster random sampling with probability proportional to
      size. The Snellen E chart was used to test visual acuity, and participants also
      underwent basic eye examination. Vision status was defined using World Health
      Organization categories of visual impairment based on presenting visual acuity
      (VA). A total of 2,954 persons were enumerated and 2,499 (84.6%) examined.
      Prevalence of blindness (presenting VA of less than 3/60 in the better eye) was
      4.1% (95% confidence interval [CI], 3.4-4.8); prevalence of low vision
      (presenting VA of at least 3/60 but less than 6/18 [corrected] in the better eye)
      was 7.7% (95% CI, 6.7-8.7); whereas prevalence of monocular visual impairment
      (presenting VA of at least 6/18 [corrected] in better eye and VA of less than
      6/18 [corrected] in other eye) was 4.4% (95% CI, 3.6-5.3). The main causes of
      blindness were considered to be cataract (41.2%) and trachoma (35.3%), whereas
      low vision was mainly caused by trachoma (58.1%) and cataract (29.3%). It is
      estimated that in Mankien payam 1,154 persons aged 5 y and above (lower and upper
      bounds = 782-1,799) are blind, and 2,291 persons (lower and upper bounds = 1,820
      2,898) have low vision. CONCLUSIONS: Blindness is a serious public health problem
      in Mankien, and there is urgent need to implement comprehensive blindness
      prevention programs. Further surveys are essential to confirm these tragic
      findings and estimate prevalence of blindness and low vision in the entire region
      of southern Sudan in order to facilitate planning of VISION 2020 objectives.

PMID- 17177597
TI  - Blinding trachoma in postconflict southern Sudan.
AB  - BACKGROUND: Trachoma is a leading cause of preventable blindness. Reports from
      eye surgery camps and anecdotal data indicated that blinding trachoma is a
      serious cause of visual impairment in Mankien payam (district) of southern Sudan.
      We conducted this study to estimate the prevalence of trachoma, estimate targets
      for interventions, and establish a baseline for monitoring and evaluation.
      METHODS AND FINDINGS: A population-based cross-sectional survey was conducted in
      May 2005. A two-stage cluster random sampling with probability proportional to
      size was used to select the sample population. Participants were examined for
      trachoma by experienced graders using the World Health Organization simplified
      grading scheme. A total of 3,567 persons were examined (89.7% of those
      enumerated) of whom 2,017 were children aged less than 15 y and 1,550 were aged
      15 y and above. Prevalence of signs of active trachoma in children aged 1-9 y
      was: trachomatous inflammation-follicular (TF) = 57.5% (95% confidence interval
      [CI], 54.5%-60.4%); trachomatous inflammation-intense (TI) = 39.8% (95% CI, 36.3%
      43.5%); and TF and/or TI (active trachoma) = 63.3% (95% CI, 60.1%-66.4%).
      Prevalence of trachomatous trichiasis was 9.6% (95% CI, 8.4%-10.9%) in all ages,
      2.3% (95% CI, 1.6%-3.2%) in children aged under 15 y, and 19.2% (95% CI, 17.0%
      21.7%) in adults. Men were equally affected by trichiasis as women: odds ratio =
      1.09 (95% CI, 0.81%-1.47%). It is estimated that there are up to 5,344 persons
      requiring trichiasis surgery in Mankien payam. CONCLUSIONS: Trachoma is a serious
      public health problem in Mankien, and the high prevalence of trichiasis in
      children underscores the severity of blinding trachoma. There is an urgent need
      to implement the surgery, antibiotics, facial cleanliness, and environmental
      change (SAFE) strategy for trachoma control in Mankien payam, and the end of the
      21-y civil war affords an opportunity to do this.

PMID- 17177598
TI  - Epidermal growth factor receptor activation in glioblastoma through novel
      missense mutations in the extracellular domain.
AB  - BACKGROUND: Protein tyrosine kinases are important regulators of cellular
      homeostasis with tightly controlled catalytic activity. Mutations in kinase
      encoding genes can relieve the autoinhibitory constraints on kinase activity, can
      promote malignant transformation, and appear to be a major determinant of
      response to kinase inhibitor therapy. Missense mutations in the EGFR kinase
      domain, for example, have recently been identified in patients who showed
      clinical responses to EGFR kinase inhibitor therapy. METHODS AND FINDINGS:
      Encouraged by the promising clinical activity of epidermal growth factor receptor
      (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced
      the complete EGFR coding sequence in glioma tumor samples and cell lines. We
      identified novel missense mutations in the extracellular domain of EGFR in 13.6%
      (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR
      mutations were associated with increased EGFR gene dosage and conferred anchorage
      independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by
      expression of these EGFR mutants were sensitive to small-molecule EGFR kinase
      inhibitors. CONCLUSIONS: Our results suggest extracellular missense mutations as
      a novel mechanism for oncogenic EGFR activation and may help identify patients
      who can benefit from EGFR kinase inhibitors for treatment of glioblastoma.

PMID- 17177599
TI  - Elevated serum levels of interferon-regulated chemokines are biomarkers for
      active human systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a serious systemic autoimmune
      disorder that affects multiple organ systems and is characterized by
      unpredictable flares of disease. Recent evidence indicates a role for type I
      interferon (IFN) in SLE pathogenesis; however, the downstream effects of IFN
      pathway activation are not well understood. Here we test the hypothesis that type
      I IFN-regulated proteins are present in the serum of SLE patients and correlate
      with disease activity. METHODS AND FINDINGS: We performed a comprehensive survey
      of the serologic proteome in human SLE and identified dysregulated levels of 30
      cytokines, chemokines, growth factors, and soluble receptors. Particularly
      striking was the highly coordinated up-regulation of 12 inflammatory and/or
      homeostatic chemokines, molecules that direct the movement of leukocytes in the
      body. Most of the identified chemokines were inducible by type I IFN, and their
      levels correlated strongly with clinical and laboratory measures of disease
      activity. CONCLUSIONS: These data suggest that severely disrupted chemokine
      gradients may contribute to the systemic autoimmunity observed in human SLE.
      Furthermore, the levels of serum chemokines may serve as convenient biomarkers
      for disease activity in lupus.

PMID- 17177600
TI  - Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism.
AB  - BACKGROUND: Skin atrophy is a common manifestation of aging and is frequently
      accompanied by ulceration and delayed wound healing. With an increasingly aging
      patient population, management of skin atrophy is becoming a major challenge in
      the clinic, particularly in light of the fact that there are no effective
      therapeutic options at present. METHODS AND FINDINGS: Atrophic skin displays a
      decreased hyaluronate (HA) content and expression of the major cell-surface
      hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for
      skin atrophy, we addressed the effect of topical administration of defined-size
      HA fragments (HAF) on skin trophicity. Treatment of primary keratinocyte cultures
      with intermediate-size HAF (HAFi; 50,000-400,000 Da) but not with small-size HAF
      (HAFs; <50,000 Da) or large-size HAF (HAFl; >400,000 Da) induced wild-type (wt)
      but not CD44-deficient (CD44-/-) keratinocyte proliferation. Topical application
      of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and
      significant skin thickening in patients with age- or corticosteroid-related skin
      atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by
      antibodies against heparin-binding epidermal growth factor (HB-EGF) and its
      receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3),
      and by tissue inhibitor of metalloproteinase-3 (TIMP-3). CONCLUSIONS: Our
      observations provide a novel CD44-dependent mechanism for HA oligosaccharide
      induced keratinocyte proliferation and suggest that topical HAFi application may
      provide an attractive therapeutic option in human skin atrophy.

PMID- 17177601
TI  - Antibodies and brain disease: a convergence of immunology and physiology.

PMID- 17177602
TI  - Selective involvement of the amygdala in systemic lupus erythematosus.
AB  - BACKGROUND: Antibodies specifically affect the amygdala in a mouse model of
      systemic lupus erythematosus (SLE). The aim of our study was to investigate
      whether there is also specific involvement of the amygdala in human SLE. METHODS
      AND FINDINGS: We analyzed a group of 37 patients with neuropsychiatric SLE (NP
      SLE), 21 patients with SLE, and a group of 12 healthy control participants with
      diffusion weighted imaging (DWI). In addition, in a subset of eight patients,
      plasma was available to determine their anti-NMDAR antibody status. From the
      structural magnetic resonance imaging data, the amygdala and the hippocampus were
      segmented, as well as the white and gray matter, and the apparent diffusion
      coefficient (ADC) was retrieved. ADC values between controls, patients with SLE,
      and patients with NP-SLE were tested using analysis of variance with post-hoc
      Bonferroni correction. No differences were found in the gray or white matter
      segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 x
      10(-6) mm2/s; p = 0.006 and 949 x 10(-6) mm2/s; p = 0.019, respectively) was
      lower than in healthy control participants (1152 x 10(-6) mm2/s). Mann-Whitney
      analysis revealed that the average ADC in the amygdala of patients with anti
      NMDAR antibodies (n = 4; 802 x 10(-6) mm2/s) was lower (p = 0.029) than the
      average ADC of patients without anti-NMDAR antibodies (n = 4; 979 x 10(-6) mm2/s)
      and also lower (p = 0.001) than in healthy control participants. CONCLUSIONS:
      This is the first study to our knowledge to observe damage in the amygdala in
      patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe
      damage in the amygdala compared to SLE patients without anti-NMDAR antibodies.

PMID- 17177606
TI  - Establishment and characterization of a tumor cell line derived from a mouse
      infected with murine gammaherpesvirus 78.
AB  - A tumor cell line, NB-78, was derived from a lymphoma from a BALB/c mouse
      infected with Murine gammaherpesvirus 78 (MHV-78). Cultures of the cells of this
      line underwent till now more than 100 passages, displaying an epitheloid
      transformed morphology and a diploid complement of 40 chromosomes. Viral antigen
      was detected in 12% of cells by immunofluorescence (IF) test. Reactivation of
      latent MHV-78 was proved by detecting infectious virus in culture medium only at
      passages 4345. The presence of viral M1, M2, M3, and M4 gene sequences in the
      genome of the cells was demonstrated by PCR. NB-78 is the first continuous cell
      line, which originates from a tumor of a MHV-78-infected host, harbors viral
      genome or at least its several genes, and produces infectious virus only rarely
      upon reactivation. It can be assumed that this cell line is primarily associated
      with MHV-78 and will serve as an invaluable tool for studying the MHV-78 latency.

PMID- 17177605
TI  - The M and N genes-based simplex and multiplex PCRs are better than the F or H
      gene-based simplex PCR for Peste-des-petits-ruminants virus.
AB  - Nucleocapsid (N), matrix (M) and hemagglutinin (H) genes-based simplex PCRs and
      an N and M genes-based multiplex PCR were developed for detection of Peste-des
      petits-ruminants virus (PPRV). The M gene PCR was the most sensitive, followed by
      N, H and an already described fusion (F) gene PCRs, as they could detect the
      virus in samples with titers of 101, 102, 104and 105 TCID50/ml, respectively. The
      multiplex PCR was as sensitive as the M gene PCR, but it had the advantage of
      differentiating PPRV from Rinderpest virus (RPV).

PMID- 17177603
TI  - DNA damage-induced Bcl-xL deamidation is mediated by NHE-1 antiport regulated
      intracellular pH.
AB  - The pro-survival protein Bcl-xL is critical for the resistance of tumour cells to
      DNA damage. We have previously demonstrated, using a mouse cancer model, that
      oncogenic tyrosine kinase inhibition of DNA damage-induced Bcl-xL deamidation
      tightly correlates with T cell transformation in vivo, although the pathway to
      Bcl-xL deamidation remains unknown and its functional consequences unclear. We
      show here that rBcl-xL deamidation generates an iso-Asp(52)/iso-Asp(66) species
      that is unable to sequester pro-apoptotic BH3-only proteins such as Bim and Puma.
      DNA damage in thymocytes results in increased expression of the NHE-1 Na/H
      antiport, an event both necessary and sufficient for subsequent intracellular
      alkalinisation, Bcl-xL deamidation, and apoptosis. In murine thymocytes and
      tumour cells expressing an oncogenic tyrosine kinase, this DNA damage-induced
      cascade is blocked. Enforced intracellular alkalinisation mimics the effects of
      DNA damage in murine tumour cells and human B-lineage chronic lymphocytic
      leukaemia cells, thereby causing Bcl-xL deamidation and increased apoptosis. Our
      results define a signalling pathway leading from DNA damage to up-regulation of
      the NHE-1 antiport, to intracellular alkalanisation to Bcl-xL deamidation, to
      apoptosis, representing the first example, to our knowledge, of how deamidation
      of internal asparagine residues can be regulated in a protein in vivo. Our
      findings also suggest novel approaches to cancer therapy.

PMID- 17177604
TI  - The RNA-binding protein KSRP promotes decay of beta-catenin mRNA and is
      inactivated by PI3K-AKT signaling.
AB  - Beta-catenin plays an essential role in several biological events including cell
      fate determination, cell proliferation, and transformation. Here we report that
      beta-catenin is encoded by a labile transcript whose half-life is prolonged by
      Wnt and phosphatidylinositol 3-kinase-AKT signaling. AKT phosphorylates the mRNA
      decay-promoting factor KSRP at a unique serine residue, induces its association
      with the multifunctional protein 14-3-3, and prevents KSRP interaction with the
      exoribonucleolytic complex exosome. This impairs KSRP's ability to promote rapid
      mRNA decay. Our results uncover an unanticipated level of control of beta-catenin
      expression pointing to KSRP as a required factor to ensure rapid degradation of
      beta-catenin in unstimulated cells. We propose KSRP phosphorylation as a link
      between phosphatidylinositol 3-kinase-AKT signaling and beta-catenin
      accumulation.

PMID- 17177607
TI  - Cloning and nucleotide analysis of the vp2 gene of a very virulent infectious
      bursal disease virus isolate from Iran.
AB  - An Iranian field isolate (IR01) of Infectious bursal disease virus (IBDV) was
      characterized by sequence analysis of its VP2 gene and protein. Comparison of the
      obtained sequences with those of IBDV isolates from other countries revealed that
      IR01 was similar to very virulent IBDV (vvIBDV) strains with the identities at
      nucleotide and amino acid levels reaching 98.198.9% and 99.199.3%, respectively.
      On the other hand, it was less similar to non-vvIBDV strains; with nucleotide and
      amino acid identities of 95.295.7% and 96.097.3%, respectively. Out of nine
      unique nucleotide differences found between IR01 and some other serotype 1
      strains only two resulted in amino acid substitutions (Ile296Val and Thr359Lys).
      In phylogenetic analysis, IR01 was closely related to Asian and European vvIBDV
      strains. Based on these results, IR01 obviously belongs to vvIBDV strains.

PMID- 17177608
TI  - SLAM expression is not downregulated by measles virus infection.
AB  - It has been reported that the signaling lymphocyte-activation molecule (SLAM),
      the second receptor of Measles virus (MV) on the cell surface appears to be
      downregulated by MV infection or by expression of MV hemagglutinin (H) (Tanaka et
      al., 2002; Welsteadt et al., 2004). The aim of this study was to analyze this
      phenomenon in more detail using a Chinese vaccine strain (S191) of MV. Flow
      cytometry confirmed apparent downregulation of SLAM in the virus-infected cells
      and in the cells transfected with a plasmid expressing viral H. Moreover, a
      similar effect was obtained by incubation of the cells with UV-inactivated virus
      or soluble viral H. Real-time quantitative PCR showed that the SLAM mRNA level
      remained stable during the virus infection, and Western blot analysis
      demonstrated that the SLAM content of total membrane proteins did not change
      change after the virus infection. Thus we conclude that SLAM expression is stable
      during the MV infection and that its apparent downregulation reported earlier and
      confirmed also in this study was just the result of masking of the antibody
      recognition sites on SLAM with MV H during the flow cytometry assay.

PMID- 17177609
TI  - Reassortment and modification of hemagglutinin cleavage motif of avian/WSN
      influenza viruses generated by reverse genetics that correlate with attenuation.
AB  - Avian influenza associated with H9N2 and H5N1 subtypes of avian influenza viruses
      (AIVs) has raised great concerns in China. To study this problem, reverse
      genetics has been employed. Three reassortants, rgH9N2, rgH5N1 and rgH5N2, were
      prepared and compared. Their hemagglutinin (HA) and neuraminidase (NA) genes
      originated from Chinese AIV isolates of H9N2 or H5N1 subtype, while the rest of
      their genes were derived from A/WSN/33(H1N1) virus (WSN). In the H5 HA
      reassortants, the multibasic cleavage site was converted to a monobasic one. The
      results demonstrated that the reassortants did not produce CPE on MDCK cells in
      the absence of trypsin, showed egg-adaptation phenotype and stability of HA and
      NA during consecutive egg passages, and were not lethal to chickens and mice.
      However, the rgH5N1 reassortant exhibited a residual virulence in terms of
      lethality to chick embryos and pathogenesis in chickens. It can be concluded that
      (i) the genetic modification of H5 HA attenuated the H5 reassortants, (ii) the
      presence of internal WSN proteins contributed to the attenuated properties of the
      reassortants independently on H5 HA, and (iii) also the overall genome
      composition contributed to virulence differences. This report provides further
      contribution of reverse genetics to the knowledge of virulence of influenza
      viruses.

PMID- 17177610
TI  - Coexpression of interleukin-2 enhances the immunization effect of a DNA vaccine
      expressing herpes simplex 1 glycoprotein D.
AB  - In this study, DNA vaccines consisting of vector IRES-gD expressing Herpes
      simplex virus 1 (HSV-1) glycoprotein D (gD) and vector IRES-gD-IL-2 coexpressing
      HSV-1 gD and interleukin-2 (IL-2), respectively, were constructed. After
      intramuscular inoculation, both vaccines induced in BALB/c mice antibodies as
      assayed by ELISA and virus neutralization. However, IRES-gD-IL-2 elicited
      significantly higher levels of IgG (ELISA) and neutralizing antibodies than IRES
      gD. Isotyping of sera from mice injected with IRES-gD-IL-2 revealed predominantly
      IgG2a antibodies. IRES-gD-IL-2 also elicited a higher delayed-type sensitivity
      (DTH) reaction. However, there was no difference in the protection against lethal
      challenge with HSV-1 between the two vaccines (P>0.05). The results suggest that
      the vaccination with IRES-gD-IL-2 can efficiently enhance the immune response of
      mice to HSV-1, particularly through increased cellular immunity.

PMID- 17177611
TI  - PrP gene polymorphism in sheep breeds in Slovakia and susceptibility to scrapie.
AB  - We analyzed the prion protein (PrP) genotype based on the codons 136, 154 and 171
      and assigned to five risk groups (R1-R5) in healthy and scrapie-affected sheep in
      Slovakia. In healthy (asymptomatic) population, 119 Merino, 106 Improved
      Valachian, 117 Tsigai, and 48 Suffolk breeds were tested. Among the asymptomatic
      sheep, the low-risk genotypes R1 and R2 were most abundant in Suffolk (94%) and
      Merino (84%) breeds, followed by Tsigai (58%) and Improved Valachian (40%)
      breeds. The medium-risk group R3 was most frequent in Improved Valachian (31%)
      breed, followed by Tsigai (21%), Merino (10%), and Suffolk (6%) breeds. The
      occurrence of high-risk groups R4 and R5 was none in Suffolk breed, followed by
      Merino (6%), Tsigai (21%), and Improved Valachian (30%) breeds. Since 2003,
      altogether 48 cases of scrapie have been confirmed in Tsigai (38), Merino (4),
      Improved Valachian (2), Improved Valachian x Tsigai (3), and Suffolk (1) breeds.
      Among sheep with scrapie, Merino breed belonged to the medium-risk group R3. The
      majority of scrapie-affected Tsigai sheep were classified into high-risk R5 (50%)
      and medium-risk R3 (42%) groups. We showed an association of scrapie with medium-
      and high-risk groups of PrP genotype in Slovakia. In particular, the glutamine at
      position 171 appears to be of major importance for the susceptibility to scrapie.

PMID- 17177612
TI  - Inhibition of UL54 and UL97 genes of human cytomegalovirus by RNA interference.
AB  - Short interfering RNAs (siRNAs), namely siUL54-1 and siU54-2 targeting UL54 (DNA
      polymerase) gene, and siUL97-1 and siUL97-2 targeting UL97 (phosphotransferase)
      gene, were used to inhibit respective genes of Human cytomegalovirus (HCMV) and
      consequently the virus infection process in human foreskin fibroblast (HFF)
      cultures. The virus infection was monitored by cell morphology (CPE), levels of
      UL83 and IE86 mRNAs, and virus antigen. The results showed that siUL97-2
      remarkably inhibited viral CPE while other siRNAs were less inhibitory. The
      siRNAs reduced the levels of UL83 mRNA but not that of IE86 mRNA; again, siUL97-2
      was most inhibitory. Particularly, siUL97-2 reduced the UL83 mRNA level 14, 19,
      203, and 37 times at 24, 48, 72, and 96 hrs post infection (p.i.), respectively.
      When tested for the effect on viral antigen by immunofluorescent assay (IFA),
      UL97-2 exerted a marked inhibition. These results demonstrate the effectiveness
      of siRNAs against experimental HCMV infection and indicate their therapeutic
      potential.

PMID- 17177613
TI  - PB1-F2 gene in influenza a viruses of different hemagglutinin subtype.
AB  - The second ORF frame (+1) of PB1 polymerase gene of Influenza A virus (IAV)
      encodes the PB1-F2 protein. The length of PB1-F2 encoded by the A/Puerto
      Rico/8/34 (H1N1) (PR8) virus is 87 aa. The analysis of nucleotide sequences of
      PB1 gene of 626 IAV isolates available in GenBank and Influenza Sequence Database
      revealed that this gene has mostly the capacity to encode a putative protein of
      90 aa. The predicted extra three amino acids in the 90-aa PB1-F2 are to a great
      extent conservative. Some IAV isolates, particularly human, avian and swine with
      hemagglutinin (HA) of H1 subtype can potentially encode a C-terminally truncated
      PB1-F2 of various lengths. The C-terminally truncated PB1-F2 in H1 isolates is
      lacking the region responsible for mitochondrial targeting and apoptosis. About
      50% of avian isolates of H9 subtype possess an ORF for truncated PB1-F2. Eighteen
      aa, 10 at the N-terminus and 8 at the C terminus are strictly conservative in all
      148 human isolates.

PMID- 17177614
TI  - Monoclonal antibody to olive latent virus 1.

PMID- 17177615
TI  - Phylogenetic characterization of rabies virus isolates from Chennai, India.

PMID- 17177616
TI  - The supposedly attenuated hy-HK variant of highly virulent Hypr strain of tick
      borne encephalitis virus is obviously a strain of Langat virus.

PMID- 17177617
TI  - Comparison of different methods of routine typing of Indian isolates of Foot-and
      mouth disease virus.

PMID- 17177618
TI  - Limbic irritability and chaotic neural response during conflicting stroop task in
      the patients with unipolar depression.
AB  - According to recent findings activation of anterior cingulate cortex (ACC) is
      related to detecting cognitive conflict. This conflict related activation elicits
      autonomic responses which can be assessed by psychophysiological measures such as
      heart rate variability calculated as beat to beat R-R intervals (RRI). Recent
      findings in neuroscience also suggest that cognitive conflict is related to
      specific nonlinear chaotic changes of the signal generated by neural systems. The
      present study used Stroop word-color test as an experimental approach to
      psychophysiological study of cognitive conflict in connection with RRI
      measurement, psychometric measurement of limbic irritability (LSCL-33),
      depression (BDI-II) and calculation of largest Lyapunov exponents in nonlinear
      data analysis of RRI time series. Significant correlation 0.61 between largest
      Lyapunov exponents and LSCL-33 found in this study indicate that a defect of
      neural inhibition during conflicting Stroop task is closely related to limbic
      irritability. Because limbic irritability is probably closely related to
      epileptiform abnormalities in the temporolimbic structures, this result might
      represent useful instrument for indication of anticonvulsant treatment in
      depressive patients who are resistant to antidepressant medication.

PMID- 17177619
TI  - Chaotic EEG patterns during recall of stressful memory related to panic attack.
AB  - Chaotic transitions likely emerge in a wide variety of cognitive phenomena and
      may be linked to specific changes during the development of mental disorders.
      They represent relatively short periods in the behavior of a system, which are
      extremely sensitive to very small changes. This increased sensitivity has been
      suggested to occur also during retrieval of stressful emotional experiences
      because of their fragmentary, temporally and spatially disorganized character. To
      test this hypothesis we recorded EEG during retrieval of fearful memories related
      to panic attack in 7 patients and retrieval of anxiety-related memories in 11
      healthy controls. Nonlinear data analysis of EEG records showed a statistically
      significant increase in degree of chaotic dynamics after retrieval of stressful
      memories in majority of patients as well as in control subjects. This change
      correlated with subjective intensity of anxiety induced during the memory
      retrieval. The data suggest a role of nonlinear changes of neural dynamics in the
      processing of stressful anxiety-related memories, which may play an important
      role in the pathophysiology of panic disorder.

PMID- 17177620
TI  - Somatosensory influence on postural response to galvanic vestibular stimulation.
AB  - We investigated how postural responses to galvanic vestibular stimulation were
      affected by standing on a translating support surface and by somatosensory loss
      due to diabetic neuropathy. We tested the hypothesis that an unstable surface and
      somatosensory loss can result in an increase of vestibulospinal sensitivity.
      Bipolar galvanic vestibular stimulation was applied to subjects who were standing
      on a force platform, either on a hard, stationary surface or during a backward
      platform translation (9 cm, 4.2 cm/s). The intensity of the galvanic stimulus was
      varied from 0.25 to 1 mA. The amplitude of the peak body CoP displacement in
      response to the galvanic stimulus was plotted as a function of stimulus intensity
      for each individual. A larger increase in CoP displacement to a given increase in
      galvanic current was interpreted as an increase of vestibulospinal sensitivity.
      Subjects with somatosensory loss in the feet due to diabetes showed higher
      vestibulospinal sensitivity than healthy subjects when tested on a stationary
      support surface. Control subjects and patients with somatosensory loss standing
      on translating surface also showed increased galvanic response gains compared to
      stance on a stationary surface. The severity of the somatosensory loss in the
      feet correlated with the increased postural sensitivity to galvanic vestibular
      stimulation. These results showed that postural responses to galvanic vestibular
      stimulus were modified by somatosensory information from the surface.
      Somatosensory loss due to diabetic neuropathy and alteration of somatosensory
      input during stance on translating support surface resulted in increased
      vestibulospinal sensitivity.

PMID- 17177621
TI  - Human postural response to lower leg muscle vibration of different duration.
AB  - Body lean response to bilateral vibrations of soleus muscles were investigated in
      order to understand the influence of proprioceptive input from lower leg in human
      stance control. Proprioceptive stimulation was applied to 17 healthy subjects by
      two vibrators placed on the soleus muscles. Frequency and amplitude of vibration
      were 60 Hz and 1 mm, respectively. Vibration was applied after a 30 s of
      baseline. The vibration duration of 10, 20, 30 s respectively was used with
      following 30 s rest. Subjects stood on the force platform with eyes closed.
      Postural responses were characterized by center of pressure (CoP) displacements
      in the anterior-posterior (AP) direction. The CoP-AP shifts as well as their
      amplitudes and velocities were analyzed before, during and after vibration.
      Vibration of soleus muscles gradually increased backward body tilts. There was a
      clear dependence of the magnitude of final CoP shift on the duration of
      vibration. The amplitude and velocity of body sway increased during vibration and
      amplitude was significantly modulated by duration of vibration as well.
      Comparison of amplitude and velocity of body sway before and after vibration
      showed significant post-effects. Presented findings showed that somatosensory
      stimulation has a long-term, direction-specific influence on the control of
      postural orientation during stance. Further, the proprioceptive input altered by
      soleus muscles vibration showed significant changes in postural equilibrium
      during period of vibration with interesting post-effects also.

PMID- 17177622
TI  - Beneficial effects of Provinols: cardiovascular system and kidney.
AB  - Red wine polyphenols have been reported to exert beneficial effects in preventing
      cardiovascular diseases but their molecular mechanisms of hemodynamic effects on
      functional cardiovascular and renal changes were studied much less. The review is
      focused on in vitro as well as in vivo effects of red wine extract containing
      polyphenolic compounds (Provinols) on cardiovascular systems and kidney in
      relation to the molecular and biochemical mechanisms of these compounds. This
      review provides the evidence that Provinols is able to produce ex vivo
      endothelium-dependent relaxation as a result of enhanced NO synthesis.
      Administration of Provinols partially prevents the development of hypertension
      during NO deficiency and accelerates the decrease of blood pressure in already
      established hypertension. The effects of Provinols include prevention and/or
      attenuation of myocardial fibrosis, reduction of aortic wall thickening and
      improvement of vascular functions. These functional and structural alterations
      are associated with significant augmentation of NO production, seen as the
      increase of NO synthase activity and eNOS protein expression. Moreover, it has
      been documented that Provinols decreased the oxidative stress within the
      cardiovascular system and kidney.

PMID- 17177623
TI  - The effect of different antioxidants on nitric oxide production in hypertensive
      rats.
AB  - The imbalance between nitric oxide (NO) and reactive oxygen species (ROS)
      production appears to be a common feature of experimental and human hypertension.
      Previously, different antioxidants and/or scavengers of oxygen free radicals were
      shown to activate nitric oxide synthase (NO synthase, NOS) and to increase the
      expression of both endothelial and neuronal NO synthase isoforms leading to blood
      pressure reduction. On the other hand, various antihypertensive drugs have been
      documented to possess antioxidant properties, which may contribute to their
      beneficial effect on blood pressure. This review is focused on the effects of
      antioxidant treatment in different models of experimental hypertension with a
      special attention to the prevention of oxidative damage and the augmentation of
      NO synthase activity and expression of NOS isoforms.

PMID- 17177624
TI  - The time-dependent effect of Provinols on brain NO synthase activity in L-NAME
      induced hypertension.
AB  - Red wine polyphenols have been reported to possess beneficial properties for
      preventing cardiovascular diseases but their neuroprotective effects during
      chronic L-NAME treatment have not been elucidated. The aim of this study was to
      analyze a time course of Provinols effects on brain NO synthase activity and
      oxidative damage in L-NAME-induced hypertension. Male Wistar rats, 12 weeks old,
      were divided into six groups: control groups, groups treated with N(G)-nitro-L
      arginine methyl ester (L-NAME, 40 mg/kg/day) for 4 or 7 weeks and groups
      receiving Provinols (40 mg/kg/day) plus L-NAME for 4 or 7 weeks. At the end of
      the treatment, marker of membrane oxidative damage - conjugated dienes (CD) in
      the brain and NO synthase activity in the cerebral cortex, cerebellum and
      brainstem were determined. L-NAME treatment for 4 or 7 weeks led to the increase
      in blood pressure, elevation of CD concentration and decrease of NO synthase
      activity in the brain parts investigated. Provinols partially prevented blood
      pressure rise and elevation of CD concentration. Comparing to the L-NAME treated
      group, Provinols increased NO synthase activity after 4 weeks of treatment.
      However, the prolonged Provinols treatment for 7 weeks had no effect on NO
      synthase activity decreased by L-NAME treatment. In conclusion, Provinols
      partially prevents L-NAME induced hypertension via the different mechanisms
      depending on the duration of treatment. Prevention of oxidative damage in the
      brain with modulating effect on NO synthase activity is suggested.

PMID- 17177625
TI  - Vascular effects of red wine polyphenols in chronic stress-exposed Wistar-Kyoto
      rats.
AB  - Present study investigated the effect of red wine polyphenolic compounds
      (Provinols) on blood pressure (BP), nitric oxide synthase (NOS) activity and
      vascular function in Wistar-Kyoto (WKY) rats exposed to chronic social stress
      produced by crowding. Adult male rats were divided into four groups: control (480
      cm(2)/rat), Provinols-treated (20 mg/kg/day, 480 cm(2)/rat), crowded (200
      cm(2)/rat) and crowded treated with Provinols (20 mg/kg/day, 200 cm(2)/rat) for 8
      weeks. No differences in BP were observed among the groups at the end of
      experiment, however, reduced BP was observed in Provinols-treated rats after 3
      weeks of treatment. NOS activity in the aorta was significantly elevated in
      crowded rats, while Provinols alone had no effect on nitric oxide (NO)
      production. Acetylcholine-induced relaxation of the femoral artery was
      significantly improved in stressed and Provinols-treated rats vs. control,
      without significant changes in their noradrenaline-induced vasoconstriction.
      Interestingly, Provinols blunted the elevation of NO production and
      vasorelaxation during crowding. Increased endothelium-dependent vasorelaxation
      and NO synthesis in crowded rats may represent the adaptation mechanisms,
      resulting in unaltered blood pressure in stress-exposed normotensive rats. This
      study further demonstrated that elevated release of NO during chronic stress may
      be prevented by Provinols. Thus, Provinols might maintain equilibrium between
      endothelium-derived vasoconstrictor and vasodilator factors in stress.

PMID- 17177626
TI  - Hereditary hypertriglyceridemic rat: a suitable model of cardiovascular disease
      and metabolic syndrome?
AB  - Hypertriglyceridemia and hypertension seem to be very important cardiovascular
      risk factors. The Prague hereditary hypertriglyceridemic (hHTG) rat was developed
      as a model of human hypertriglyceridemia. It was demonstrated that these rats are
      not obese, they are hypertensive and insulin resistant and they have some
      disturbances in glucose metabolism. Several QTLs were identified for blood
      pressure, its particular components (dependent on major vasoactive systems) and
      plasma triglycerides throughout the genome of hHTG rats by using of F(2) hybrids
      strategy. It is evident that hHTG rats are a suitable model for the study of
      metabolic disturbances in relation to blood pressure as well as for the search of
      genetic determinants of these abnormalities. Numerous abnormalities of blood
      pressure regulation as well as alterations in the structure and function of
      cardiovascular apparatus (heart, conduit and resistance arteries) were found in
      hHTG rats. A special attention was paid to possible changes in the efficiency of
      various vasoactive systems such as nitric oxide, renin-angiotensin-aldosterone
      system and sympathetic nervous system, which seem to contribute substantially to
      cardiovascular and/or metabolic abnormalities observed in Prague hereditary
      hypertriglyceridemic rats.

PMID- 17177627
TI  - Functional and structural pattern of arterial responses in hereditary
      hypertriglyceridemic and spontaneously hypertensive rats in early stage of
      experimental hypertension.
AB  - It has been shown that endothelium-derived nitric oxide (NO) plays an important
      role in regulation of vascular tone in the prenatal and early postnatal period.
      The aim of this paper was to determine the reactivity and accompanying structural
      changes in thoracic aorta from 4-week-old spontaneously hypertensive rats (SHR)
      and rats with hereditary hypertriglyceridemia (hHTG) in comparison with age
      matched normotensive controls. For functional studies thoracic aorta was excised,
      cut into rings and mounted in organ baths for measurement of isometric
      contractile force. For morphological studies cardiovascular system of rats was
      perfused with glutaraldehyde fixative (at 100 mm Hg) via cannula placed in the
      left ventricle. Morphological changes of thoracic aorta were measured using light
      microscopy. Systolic blood pressure (SBP) in SHR (98+/-1 mm Hg) did not
      significantly differ from that of age-matched control rats (95+/-4 mm Hg), but
      was slightly increased in hHTG rats (110+/-2 mm Hg, P<0.05). Heart weight/body
      weight ratio was higher in SHR and hHTG rats than in control group indicating the
      hypertrophy of the heart in both models of hypertension. Endothelium-dependent
      relaxation of aorta induced by acetylcholine was preserved in all groups and did
      not differ from that in control normotensive rats. The maximal isometric
      contraction of thoracic aorta to noradrenaline (NA) was reduced in hypertensive
      groups and the concentration-response curves to NA were shifted to the right
      indicating increased sensitivity of smooth muscle to NA. The values of wall
      thickness and cross sectional area as well as inner diameter of thoracic aorta in
      SHR and hHTG rats were significantly decreased in comparison to control groups.
      Endothelial dysfunction seems to be absent in all young rats before development
      of hypertension. In conclusion, our observations indicate that in early stage of
      experimental hypertension NO-dependent relaxation is preserved so that putative
      impairment of this function provides no significant pathogenic contribution to
      the onset of hypertension in these two experimental models.

PMID- 17177628
TI  - Comparison of vascular function and structure of iliac artery in spontaneously
      hypertensive and hereditary hypertriglyceridemic rats.
AB  - The aim of this study was to compare the vascular reactivity and morphology of
      iliac artery (IA) in adult spontaneously hypertensive rats (SHR) and hereditary
      hypertriglyceridemic (hHTG) rats. The isolated rings of iliac artery (IA) from
      Wistar rats (controls), SHR and hHTG rats were used for measurement of relaxant
      responses to acetylcholine (ACh) and contractile responses to noradrenaline (NA).
      Morphological changes of IA were measured using light microscopy. Systolic blood
      pressure (BP) measured by plethysmographic method was increased in SHR
      approximately by 88 % and in hHTG rats by 44 % compared to controls. BP increase
      was accompanied by cardiac hypertrophy. In both SHR and hHTG groups (experimental
      groups) reduced relaxation to ACh and enhanced maximal contraction and
      sensitivity to adrenergic stimuli were observed. The sensitivity to NA in SHR was
      higher also in comparison with hHTG. Geometry of IA in both experimental groups
      revealed increased wall thickness and wall cross-sectional area, in SHR even in
      comparison with hHTG. Inner diameter was decreased in both experimental groups.
      Thus, independently of etiology, hypertension in both models was connected with
      impaired endothelial function accompanied by structural alterations of IA. A
      degree of BP elevation was associated with arterial wall hypertrophy and
      increased contractile sensitivity.

PMID- 17177629
TI  - Differential remodeling of carotid artery in spontaneously hypertensive and
      hereditary hypertriglyceridemic rats.
AB  - High blood pressure, increased level of cholesterol, diabetes,
      hypertriglyceridemia and obesity are risk factors accompanied metabolic syndrome.
      The aim of the study was to compare geometry of carotid artery (AC) of 3-week-old
      (3w) and 52-week-old (52w) hereditary hypertriglyceridemic rats (hHTG) and
      spontaneously hypertensive rats (SHR) which represent a genetic model of human
      essential hypertension with age-matched Wistar rats. After sacrificing the rats
      were perfused with a glutaraldehyde fixative under the pressure 90 mm Hg (3w) and
      120 mm Hg (52w) for 10 min via cannula placed into left ventricle. Middle part of
      AC was excised and processed according to standard electron microscopy procedure.
      Geometry of AC was evaluated in light microscopy. SHR vs. Wistar rats: BP of 3w
      did not differ, in 52w it was increased; cardiac hypertrophy was found in both
      ages; wall thickness (WT) and cross sectional area (CSA) in 3w did not differ, in
      52w both were increased; inner diameter (ID) in 3w and 52w was decreased; WT/ID
      was increased in both ages. Hereditary HTG vs. Wistar rats: BP was increased in
      both periods; cardiac hypertrophy was observed in 3w; WT in 3w was decreased, in
      52w it was increased; CSA and ID were decreased in both ages; WT/ID was increased
      only in 52w. Discrepancies between development of BP, cardiac hypertrophy in SHR
      and hHTG rats were observed. Alterations of BP were not in harmony with
      alterations in geometry of carotid arteries in both SHR and hHTG rats. We suggest
      that BP is not the main stimuli evoked hemodynamic and structural alterations of
      cardiovascular system in ontogenic development of SHR and hHTG rats.

PMID- 17177630
TI  - Acetylcholinesterase inhibition affects cardiovascular structure in mice.
AB  - Experiments were performed in C57BL/6J male mice to determine the effects of
      acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB) and stress on
      cardiovascular function, structure, and apoptosis. Mice were studied for seven
      days under the following conditions: Controls (osmotic minipump with saline), PB
      (10 mg/kg/day, minipumps), shaker stress (45 stressors/day, minipump with saline)
      and PB+Stress combination. AChE activity was significantly reduced in all PB
      treated mice. PB caused no changes in 24-h mean arterial pressure (MAP) or heart
      rate (HR). Stress increased 24-h MAP on day 1 and 24-h HR on day 7 in both Stress
      and PB+Stress groups. A significant reduction in the aortic wall
      thickness/diameter ratio (P <0.05 vs. control) and slightly reduced relative
      heart weight were observed in the PB group. These effects were blunted by
      simultaneous stress exposure. Immunochemistry was used to stain for Bax and Bcl-2
      (apoptosis markers). There was a four-fold increase in Bax/Bcl-2 ratio in the
      heart of PB and PB+Stress treated mice while an attenuation was observed in
      aortic endothelium. Results suggest that a relatively short-term continuous PB
      exposure may have adverse effects on the heart and blood vessels, independently
      of changes in MAP and HR.

PMID- 17177631
TI  - The effect of psychoemotional load on ventricular repolarization reflected in
      integral body surface potential maps.
AB  - The aim of the present study was to investigate the reflection of psychoemotional
      stress in the body surface potential distribution as documented by isointegral
      maps of cardiac activation and recovery. In 72 young men (18.3+/- 7.3 y.) with no
      cardiovascular history body surface potential maps (BSPMs) at rest and during the
      test of mental arithmetic were recorded. The digitalized data for each point of
      the QRS, STT and QRST integral maps, for each subject in both situations, were
      processed and evaluated by methods of univariate as well as spatial mathematical
      and statistical modeling. The results showed during MA a significant decrease of
      repolarization integral values over the sternum and right precordium, which
      contributed to analogically localized decrements also in the QRST BSM. The
      decrease occurred in more than 2/3 of lead points. The most pronounced changes
      were observed in the right precordial area, where potentials decreased in more
      than in 70 % of subjects. In conclusion, the discriminative power of the
      difference STT and QRST integral maps was strong enough to distinguish the mental
      arithmetic induced changes in the superficial cardiac electric field. These
      adrenergic transient alterations in ventricular recovery may be of importance in
      subjects at risk for ventricular arrhythmias.

PMID- 17177632
TI  - Effects of caffeine at different temperatures on contractile properties of slow
      twitch and fast-twitch rat muscles.
AB  - The slow-twitch soleus muscle (SOL) exhibits decreased twitch tension (cold
      depression) in response to a decreased temperature, whereas the fast-twitch
      extensor digitorum longus (EDL) muscle shows enhanced twitch tension (cold
      potentiation). On the other hand, the slow-twitch SOL muscle is more sensitive to
      twitch potentiation and contractures evoked by caffeine than the fast-twitch EDL
      muscle. In order to reveal the effects of these counteracting conditions
      (temperature and caffeine), we have studied the combined effects of temperature
      changes on the potentiation effects of caffeine in modulating muscle contractions
      and contractures in both muscles. Isolated muscles, bathed in a Tyrode solution
      containing 0.1-60 mM caffeine, were stimulated directly and isometric single
      twitches, fused tetanic contractions and contractures were recorded at 35 degrees
      C and 20 degrees C. Our results showed that twitches and tetani of both SOL and
      EDL were potentiated and prolonged in the presence of 0.3-10 mM caffeine. Despite
      the cold depression, the extent of potentiation of the twitch tension by caffeine
      in the SOL muscle at 20 degrees C was by 10-15 % higher than that at 35 degrees
      C, while no significant difference was noted in the EDL muscle between both
      temperatures. Since the increase of twitch tension was significantly higher than
      potentiation of tetani in both muscles, the twitch-tetanus ratio was enhanced.
      Higher concentrations of caffeine induced contractures in both muscles; the
      contracture threshold was, however, lower in the SOL than in the EDL muscle at
      both temperatures. Furthermore, the maximal tension was achieved at lower
      caffeine concentrations in the SOL muscle at both 35 degrees C and 20 degrees C
      compared to the EDL muscle. These effects of caffeine were rapidly and completely
      reversed in both muscles when the test solution was replaced by the Tyrode
      solution. The results have indicated that the potentiation effect of caffeine is
      both time- and temperature-dependent process that is more pronounced in the slow
      twitch SOL than in the fast-twitch EDL muscles.

PMID- 17177633
TI  - The influence of hormonal changes during menstrual cycle on serum adiponectin
      concentrations in healthy women.
AB  - Adiponectin is an adipocyte-derived hormone involved in the regulation of
      carbohydrate and lipid metabolism. Its concentrations are decreased in patients
      with obesity, type 2 diabetes and atherosclerosis and are higher in females than
      in males. Gender differences of adiponectin levels raise the possibility that sex
      hormones directly regulate its serum concentrations, which may in turn influence
      insulin sensitivity in different phases of the menstrual cycle. To test this
      hypothesis we measured serum adiponectin, estradiol, progesterone, luteinizing
      hormone and follicle-stimulating hormone concentrations daily throughout the
      menstrual cycle in six healthy women. Mean adiponectin levels strongly positively
      correlated with serum cortisol concentrations [R=0.94286; p=0.0048 (Spearman
      correlation test)], but were not significantly related to other anthropometric,
      biochemical and hormonal characteristics of the subjects (BMI, blood glucose,
      insulin, testosterone, prolactin, cholesterol, HDL cholesterol, LDL cholesterol,
      triglycerides concentrations, or atherogenic index). Furthermore, no significant
      changes of serum adiponectin levels were found throughout the menstrual cycle. We
      conclude that changes in sex hormones during the menstrual cycle do not affect
      total circulating adiponectin levels in healthy women. Therefore, the differences
      in insulin sensitivity in various phases of the menstrual cycle are not due to
      changes of circulating adiponectin levels.

PMID- 17177634
TI  - CD8+ natural killer cells have a potential of a sensitive and reliable
      biodosimetric marker in vitro.
AB  - The aim of our work was to evaluate peripheral blood lymphocyte subsets as in
      vitro indicators of the received dose of ionizing radiation (biodosimetric
      markers) in the range of 3-20 Gy and to determine the appropriate time interval,
      during which a dose-dependent induction of apoptosis occurs upon gamma
      irradiation. In lymphocyte subsets characterized by double color surface
      immunophenotyping, four-color flow cytometry was used for visualizing cell death
      associated increase in superficial phosphatidylserine exposure and cytoplasmic
      membrane permeability by fluorinated Annexin V and propidium iodide,
      respectively. No differences between sham-treated and lethal dose (7 Gy)
      irradiated samples were observed upon 6 h cultivation in vitro. Ten and 18 h
      later, about 50 % of lymphocytes were apoptotic, but only the minority of them
      was in the late apoptotic phase. The only difference in radioresistance of the
      CD4(+)CD8(-) and CD4(-)CD8(+) lymphocyte subsets was seen upon 2-day cultivation
      when huge depletion of intact cells and prevalence of the late apoptotic
      population became obvious. A dose-dependence study in 16 and 48 h cultures
      confirmed the effectiveness of major T cell subsets as biodosimetric indicators.
      On the other hand, the minor CD8(+) subset of natural killer (NK) cells has been
      identified as a radiosensitive lymphocyte population the disappearance of which
      correlated with the received dose. We demonstrated that the CD3(-)CD8(+)NK subset
      can be used as a lethal/sublethal dose discriminator to 16 h cultivation. In
      addition, our data indicate that two-day cultivation followed by CD3/CD8
      expression analysis in an intact lymphocyte population may provide a clue for low
      dosage biodosimetry.

PMID- 17177635
TI  - Levels of myosin heavy chain mRNA transcripts and protein isoforms in the fast
      extensor digitorum longus muscle of 7-month-old rats with chronic thyroid status
      alterations.
AB  - We have studied the effect of chronic thyroid status alterations on the myosin
      heavy chain (MyHC) isoform composition (by SDS-PAGE) and on MyHC mRNA levels (by
      RT-PCR) in the fast extensor digitorum longus (EDL) muscle of 7-month-old inbred
      Lewis strain female rats and compared this with corresponding results of the
      previously studied slow soleus muscle. Our findings show that in the EDL muscle,
      all four types 1, 2a, 2x/d and 2b of MyHC mRNA transcripts and protein isoforms
      are present in euthyroid, hypothyroid and hyperthyroid rats, i.e. after chronic
      treatment with methimazole and T(3), respectively. This is in contrast with the
      soleus, where only MyHC1 and 2a protein isoforms are expressed under similar
      conditions. Except for 2x/d MyHC mRNA transcripts in the EDL muscles, there was
      always significant difference between hypothyroid and hyperthyroid rats both at
      mRNA and protein levels. From our results we can conclude that extended
      alteration of the thyroid status leads to typical changes in the expression of
      MyHC mRNA transcripts and MyHC protein isoforms in the fast EDL and the slow
      soleus muscles. These changes correspond to those described after shorter periods
      of altered thyroid status. The characteristic phenotype differences between
      soleus and EDL muscles remain, however, preserved even after 7 months of thyroid
      hormone status alteration.

PMID- 17177636
TI  - Erythrocyte ion transport in rats subjected to acute and chronic hypobaric
      hypoxia.
AB  - Our study addresses selected parameters of rat erythrocyte ion transport (Na(+)
      K(+) pump, Na(+)-K(+)-2Cl- cotransport, and passive cation fluxes) after acute or
      chronic hypoxia exposure. We did not find any significant change of ion transport
      after acute hypoxia. However, chronic hypoxia could modify ion transport because
      the affinity of Na(+)-K(+) pump for intracellular Na(+) seems to be decreased.

PMID- 17177637
TI  - Hidden branches: developments in root system architecture.
AB  - The root system is fundamentally important for plant growth and survival because
      of its role in water and nutrient uptake. Therefore, plants rely on modulation of
      root system architecture (RSA) to respond to a changing soil environment.
      Although RSA is a highly plastic trait and varies both between and among species,
      the basic root system morphology and its plasticity are controlled by inherent
      genetic factors. These mediate the modification of RSA, mostly at the level of
      root branching, in response to a suite of biotic and abiotic factors. Recent
      progress in the understanding of the molecular basis of these responses suggests
      that they largely feed through hormone homeostasis and signaling pathways. Novel
      factors implicated in the regulation of RSA in response to the myriad endogenous
      and exogenous signals are also increasingly isolated through alternative
      approaches such as quantitative trait locus analysis.

PMID- 17177638
TI  - Leaf senescence.
AB  - Leaf senescence constitutes the final stage of leaf development and is critical
      for plants' fitness as nutrient relocation from leaves to reproducing seeds is
      achieved through this process. Leaf senescence involves a coordinated action at
      the cellular, tissue, organ, and organism levels under the control of a highly
      regulated genetic program. Major breakthroughs in the molecular understanding of
      leaf senescence were achieved through characterization of various senescence
      mutants and senescence-associated genes, which revealed the nature of regulatory
      factors and a highly complex molecular regulatory network underlying leaf
      senescence. The genetically identified regulatory factors include transcription
      regulators, receptors and signaling components for hormones and stress responses,
      and regulators of metabolism. Key issues still need to be elucidated, including
      cellular-level analysis of senescence-associated cell death, the mechanism of
      coordination among cellular-, organ-, and organism-level senescence, the
      integration mechanism of various senescence-affecting signals, and the nature and
      control of leaf age.

PMID- 17177640
TI  - Injection pressure as a marker of intraneural injection in procedures of
      peripheral nerves blockade.
AB  - The blockade of peripheral nerves carries a certain risk of unwanted
      complications, which can follow after unintentional intraneural injection of a
      local anesthetic. Up till today, the research of measuring injection pressure has
      been based on animal models, even though the histological structure of periphery
      nerve is different for animal and human population, so the application pressure
      which presages intraneural injection in human population is still unknown. As
      material in performing this study there have been used 12 Wistar rats and 12
      delivered stillborns. After bilateral access to the median nerve, we applied 3 ml
      of 2% lidocaine with epinephrine, with the help of automatic syringe charger. The
      needle was at first placed perineural on one side, and then intraneural on the
      other side of both examination groups. During every application the pressure
      values were monitored using the manometer, and then they were analyzed by special
      software program BioBench. All perineural injections resulted with the pressure <
      or = 27.92 kPa, while the majority of intraneural injections were combined with
      the injection pressure > or = 69.8 kPa. The difference between intraneural and
      perineural injection pressures for the two different examination groups (rats and
      delivered stillborns) was not statistically significant (P>0.05). As prevention
      from intraneural injections today are in use two methods: the method of causing
      paresthesia or the method of using the peripheral nerve stimulator. However the
      nerve injury can still occur, independent from the technique used. If our results
      are used in clinical practice on human population, than the high injection
      pressure could be the marker of intraneural lodging of a needle.

PMID- 17177642
TI  - The role of pineal gland and exogenous melatonin on the irradiation stress
      response of suprarenal gland.
AB  - Pineal gland has and antistressogenic role. Its main hormone, melatonin, has
      radio protective effect on endocrine and other dynamic tissues. In our previous
      study, we have shown that pinealectomy changes the behavior of suprarenal gland
      in totally irradiated rats. The aim of this study is to evaluate the effect of
      exogenous melatonin on suprarenal gland of rats with or without pineal gland.
      Four months after pinealectomy (experimental group) or shampinealectomy (control
      group), adult Wistar male rats were daily treated with 0,2 mg of melatonin
      intraperitoneally, during two weeks. Thereafter, all animals were totally
      irradiated with 8 Gy of Gamma rays produced from Cobalt 60. Animals who survived
      were sacrificed on the 17(th) post irradiation day. Qualitative and quantitative
      characteristics of the suprarenal gland were studied using histological methods.
      The results show that exogenous melatonin had protective role on suprarenal gland
      in totally irradiated rats and that those effects were more pronounced in the
      presence of pineal gland.

PMID- 17177643
TI  - Treatment of left anterior descending artery aneurysm.
AB  - Coronary artery aneurysms (CAAs) are rare and their management is controversial.
      Their incidence varies from 1,5% to 5% of the coronary angiographies, with
      predilection of the right coronary artery. Unruptured coronary aneurysms are
      often silent and may remain undiagnosed. The etiology can be either congenital or
      acquired. We describe a case of a left anterior descending artery (LAD) aneurysm
      treated with an off-pump surgical revascularization with a LIMA to LAD without
      exclusion or ligature of the aneurysm.

PMID- 17177641
TI  - Hepatitis C infection in risk groups.
AB  - Hepatitis C infection is important global health problem with wide spectrum of
      health, social and economic consequences. The goal of this research was to
      estimate prevalence of hepatitis C virus infection in risk groups, and to
      determine association hepatitis C virus (HCV) infection and risk factors.
      Research included 4627 subjects divided in two groups. Test group included 2627
      subjects divided in 4 subgroups with risk for HCV infection: those who received
      blood transfusion without screening on HCV (it was introduced in 1995) (700);
      intravenous drug users (60); patients on hemodialysis (168) and health care
      workers (1699). Control group included 2000 healthy volunteer blood donors. In
      all subjects anti-HCV antibodies were tested with third generation ELISA test.
      Positive serum samples were tested for presence of HCVRNA, using reaction of
      reverse transcription and polymerase chain reaction. In all anti-HCV positive
      subjects further epidemiological and clinical workup was performed. Prevalence of
      HCV infection in risk groups was: 4.6% in subjects who have received blood
      transfusions without HCV blood screening, 35% in intravenous drug users, 58.9% in
      patients on chronic dialysis, and 0.4% in health care workers. In control group
      prevalence was low (0.2%). In the group of 158 anti-HCV positive subjects, 73.4%
      had HCVRNA. The largest number of subjects with HCV infection was in the age
      group of 30-49 years (45.8%). This study showed that multiple blood transfusions
      before introducing the blood screening for HCV, longer duration of intravenous
      drug abuse, longer duration of hemodialysis treatment, larger number of
      accidental injuries in health care workers are independent and statistically
      significant risk factors for those groups examined. Results of this study confirm
      that general screening for HCV infection is recommended in risk groups for HCV
      infection in order to identify to prevent and to treat it.

PMID- 17177644
TI  - Osteometry of mandibular joint surface.
AB  - Anatomically and functionally, temporomandibular joint (articulatio
      temporomandibularis) is specific, It consists of incongruent joint surface. The
      size of mandibular joint surface and its position in relation to facies
      articularis fossae mandibularis in different positions of mandibulae (central
      occlusion, central relation) are still subject to the interest of prosthetics.
      The aim of the research is measuring the lower joint surface by special 3D device
      that enables acribic precise measuring. Macerated human skulls, property of the
      Anatomy Institute, Faculty of Medicine, University Sarajevo, were used for the
      research that has been carried out. Results of measuring of articulating surface
      caput mandibulae along longer axis (mediolateral diameter) indicate that there
      are no differences in size of this surface between right and left joints. Results
      of measuring of articulating surface caput mandibulae along shorter axis
      (anteroposterior diameter) indicate differences in values of this diameter
      between right and left sides. Judging by statistical evaluation, differences are
      highly significant on the level of probability p<0.01. The research has shown
      differences in the size of this joint surface, on right and left sides, but only
      in antero-posterior direction. This original scientific work will help better of
      relationship of TMJ surfaces, what is necessary for treatment of TMD and occlusal
      imbalances.

PMID- 17177645
TI  - The role of collateral circulation in preserving myocardial function.
AB  - The coronary collateral circulation is an alternative source of blood supply to
      the myocardium jeopardized by the failure of the original stenotic or occluded
      vessel to provide adequate blood flow to this region. One hundred coronary
      angiograms and left ventriculograms of patients with coronary artery disease from
      the Cardiology Department of University Clinics Centre in Sarajevo were reviewed.
      The role of collateral circulation in preserving myocardial function was assessed
      by comparing regional left ventricular contractility in 34 instances of total
      arterial occlusion and adequate colateral circulation with that in 34 instances
      of total arterial occlusion and inadequate collateral circulation. Among the
      group with adequate collaterals, regional left ventricular contraction was normal
      in 41%, hypokinetic in 53% and akinetic or dyskinetic in only 5%. Among the group
      with inadequate collaterals, regional contraction was normal in 9%, hypokinetic
      in 20 % and akinetic or dyskinetic in 70%. These data indicate that collateral
      circulation plays an important role in preserving myocardial contractility in
      patients with coronary artery disease.

PMID- 17177646
TI  - Saliva and serum lithium monitoring in hospitalized patients and possibility to
      replace serum to saliva.
AB  - The lithium ions concentration in human serum and saliva was determined using dry
      slide technology Vitros 250 Analyser (Ortho Clinical Diagnostic) and atomic
      absorption spectrometry Perkin Elmer 403 (AAS). We analyzed lithium ions in 100
      serum and saliva specimens of patients after oral administration of lithium
      carbonate (3 x 300 mg) Jadran, Galen Laboratory Rijeka. Saliva and blood were
      taken 2 and 12 hours after the last dose. At the same time lithium ions at
      samples of blood and saliva were determined with both methods which showed high
      level of correlation. The mean difference of lithium ions between saliva and
      serum was statistically significant for p<0.05 using t student test. At saliva we
      got constant of elimination Kel = 0.02(-1)h and elimination half life (t(1/2))
      was t(1/2)=34.6 h. For serum was t(1/2)= 24 h what means that lithium ions
      elimination is slower from saliva then from serum. That is the reason why
      probably concentration at saliva is higher then at serum. Lithium elimination is
      two compartment pharmacokinetic model where important part of compartment are
      saliva and salivary glands. At a certain point in medical treatment it could be
      expected to use controlled determination of lithium ions in saliva with serum as
      control.

PMID- 17177647
TI  - Erythropoietin in cardiorenal anemia syndrome.
AB  - Incidents of heart and renal failure (HF, RF) together, are increasing in our
      country and all over the world, so a great attention has been dedicated to this
      problem recently. These diseases together have shown bad results because of the
      process of accelerated arteriosclerosis, structural changes of myocardium,
      oxidative stress, inflammation, increased activities of sympathetic nervous
      system (SNS), increased activities of a renin-angiotensin-aldosterone system
      (RAAS) (1). These factors are crucial in the development of patho-physiological
      process and consequential development of anemia, that together with heart and
      renal failure through interaction, cause serious disorder that we call the cardio
      renal anemia syndrome (2). We examined effects of erythropoietin (Epoetin beta)
      at 90 (60 men and 30 women) pre-dialysed and dialysed patients with HF signs
      during a period of three years in individual dozes of 2000-6000 units
      subcutaneous (sc) weekly. Using computer S PLUS and SAS multiple variant analysis
      we have got correlations by Pearson. Epoetin beta significantly develops anemia
      parameters: number of erythrocytes (r=0.51779; p<0.0001), hemoglobin (r=0.38811;
      p<0.0002), MCV (r=0.59876; p<0.0001) at patients with HF. Positive effects are
      seen at NYHA class (r=0.59906; p<0.0001), on quality of life before and after
      prescribing medicine. Parameters of renal functions are improving: more urea (r
      =0.45557; p<0.0001) than creatinine (r=0.26397; p<0.00119) and potassium values
      K(+)) are not changed significantly (r=0.02060; p<0.8471). Epoetin beta has been
      useful in treatment of pre-dialysed and dialysed patients with HF and anemia by
      improving functional ability of myocardium and quality of life.

PMID- 17177648
TI  - Lymphoscintigraphy and radiation--occupational exposure during sentinel node
      assay.
AB  - Ionizing radiation has many practical applications, but it is also, as it is well
      known, dangerous to human health. The purpose of this study was to estimate the
      dose and exposure for medical staff involved in sentinel node assay and to
      determine how safe this assay really is. The theoretical method was used for
      calculation. Three groups of medical staff were selected: nuclear medicine
      specialist, nuclear medicine technologist and a surgeon. The results obtained
      show that the most exposed staff member is nuclear medicine specialist and that
      dose received by the surgeon is smaller then the dose limit.

PMID- 17177649
TI  - Laparoscopy after previous laparotomy.
AB  - Following the abdominal surgery, extensive adhesions often occur and they can
      cause difficulties during laparoscopic operations. However, previous laparotomy
      is not considered to be a contraindication for laparoscopy. The aim of this study
      is to present that an insertion of Veres needle in the region of umbilicus is a
      safe method for creating a pneumoperitoneum for laparoscopic operations after
      previous laparotomy. In the last three years, we have performed 144 laparoscopic
      operations in patients that previously underwent one or two laparotomies.
      Pathology of digestive system, genital organs, Cesarean Section or abdominal war
      injuries were the most common causes of previous laparotomy. During those
      operations or during entering into abdominal cavity we have not experienced any
      complications, while in 7 patients we performed conversion to laparotomy
      following the diagnostic laparoscopy. In all patients an insertion of Veres
      needle and trocar insertion in the umbilical region was performed, namely a
      technique of closed laparoscopy. Not even in one patient adhesions in the region
      of umbilicus were found, and no abdominal organs were injured.

PMID- 17177650
TI  - Incomplete intestinal metaplasia as an indicator for early detection of gastric
      carcinoma in the events of helicobacter pylori positive chronic atrophic
      gastritis.
AB  - The aim of the study was to ascertain the existence of intestinal metaplasia in
      gastric mucosa of patients with gastric carcinoma coupled with H. pylori positive
      chronic atrophic gastritis and possible connection of IM with the development of
      gastric carcinoma. The paper presents prospective study that included 50 patients
      with gastric carcinoma and 50 patients with chronic atrophic H. pylori positive
      gastritis. All the patients were subjected to gastroscopy as well as biopsy
      targeted at antrum, lesser curvature and corpus and at the area 1-2 cm removed
      from tumor lesion. Biopsy samples were sliced by microtome and stained. We
      analyzed presence, frequency and severity of inflammatory-regenerative,
      metaplastic and dysplastic changes in the mucosa and evaluated their prognostic
      value. We typed IM immunohistochemically. This study confirmed responsibility of
      H. pylori for inflammatory events in gastric mucosa in patients with gastric
      carcinoma. According to our findings incomplete IM of types IIa and IIb as
      precancerous lesion is responsible for the development of gastric carcinoma and
      is associated with chronic atrophic gastritis grade I and II (92% of subjects,
      p=0.0097, h=1, p=0.01). Thus, the finding of incomplete intestinal metaplasia may
      be used as an indicator for early gastric carcinoma detection. Patients with
      patho-histologically verified incomplete intestinal metaplasia associated with
      active chronic atrophic gastritis of levels I and II represent risk group for the
      development of gastric carcinoma of intestinal type.

PMID- 17177651
TI  - Effect of war and postwar genotoxins on micronuclei frequency in Sarajevo study
      group.
AB  - During the 1992-1995 siege, as well as after the war activities, citizens of
      Sarajevo were most probably exposed to various potential genotoxic agents. The
      effects of those potential genotoxins were evaluated by micronucleus-cytokinesis
      blocked assay. The study included 30 individuals who resided in the area of
      Sarajevo during the war and the postwar period. Point bi-serial coefficient
      analysis did not reveal any relationship between the frequencies of binuclear
      cells with micronuclei as well as total number of micronuclei and smoking habits
      or gender. Simple linear regression revealed statistically significant positive
      correlation between the age and micronuclei formation. Due to the war related
      environmental contamination more extensive study is recommended.

PMID- 17177652
TI  - Cyclooxygenase-2 expression determines neo-angiogenesis in gallbladder
      carcinomas.
AB  - Neo-angiogenesis may have an important role in the poor prognosis of gallbladder
      carcinoma. An enhanced expression of COX-2 was found in precancerous lesions and
      in gallbladder carcinoma, likely to be involved in carcinogenesis as well as in
      angiogenesis. To study the relationships between the COX-2 expression and degree
      of vascularization, as well as to evaluate their role in the prognosis of
      patients with gallbladder carcinoma. 27 cases of gallbladder adenocarcinoma were
      included, classified grading I-III according the WHO classification. The COX-2
      and endothelial antigen CD105 expressions were assessed immunohistochemically.
      COX-2 expression was evaluated according to the percentage and staining intensity
      of positive cells into "COX-2 positive" and "COX-2 negative" groups. In order to
      assess tumor microvessel density (MVD), CD105 positively stained microvessels
      were counted for each specimen in predominantly vascular areas (hot spots) at 200
      x magnification. The MVD ranged from 9 to 46 microvessels/field. 15 tumors
      belonged to the hypervascular group (MVD > or = 25) and 12 to the hypovascular
      group. There were 16 (59.2%) COX-2 positive cases. There was difference in the
      degree of angiogenesis between COX-2 positive vs. COX-2 negative group: 11
      (68.8%) out of 16 "COX-2 positive" tumors were hypervascular, in comparison with
      just 4 (36.4%) of "COX-2 negative" tumors. Our data show that the MVD corresponds
      to the COX-2 overexpression in gallbladder carcinomas. Augmented tumor
      neovascularization induced by COX-2 might be responsible for the poor prognosis
      in gallbladder carcinoma patients.

PMID- 17177653
TI  - Effects of amitryptiline administration on rat sera and brain beta-endorphins.
AB  - The aim of our study was to establish the influence of antidepressive drugs on
      serum and brain beta-endorphins in experimental animals. Experiment was performed
      on albino Wistar rats. Antidepressant amitryptiline was used, and for
      quantification of sera and brain beta-endorphins RIA technique. Our results
      showed difference between sera and brain beta-endorphins concentration in
      amitryptiline pretreated animals, vs. those in serum and brain of control group
      treated with 0.95% NaCl. This study shows that use of psychoactive drugs have
      influence on sera and brain beta-endorphins concentration. Beta-endorphins could
      be of great importance, used as markers for evaluation of antidepressant drug
      effects.

PMID- 17177654
TI  - Cancer mortality, recent trends and perspectives.
AB  - Considering that a register for cancer was established in Federation of Bosnia
      and Herzegovina only recently, basic reliable source for the analysis of cancer
      mortality trends are the data on death cases caused by such diseases. Lack of
      census as well as standardized mortality rate data makes the study even more
      difficult to make. The aim of the study is the analysis of the malign diseases
      trend in the post-war period according to the available data. The study is the
      descriptive work on the analysis of the system using linear regression methods
      for expected trend for the total population and age group from 0 to 64 years.
      Registered rate of cancer mortality in Federation of Bosnia and Herzegovina in
      2004 was 142 per 100000 inhabitants, and indicates input stream in the analyzed
      period. Total increase in mortality of males and females is 2.5% per year. It is
      expected that in 2020 around 5000 inhabitants of Federation of Bosnia and
      Herzegovina will die of some malign disease. Trend of mortality of malign
      diseases in males is higher than in females and more probable in older
      population. There is a tendency of mortality decrease in the group of 0-64 years
      of age. Mortality list of the most frequent locations of cancer has undergone
      changes. Liver cancer, colon cancer, sigma and rectum cancer as well as lung and
      breast cancer lead the list. Objective ageing of the population, technological
      drawbacks, insufficient primary and secondary prevention worsened by socio
      economic life conditions will affect the increase in number of people with malign
      diseases in Bosnia and Herzegovina.

PMID- 17177655
TI  - Specificity of electrocardiography and echocardiography changes at the patients
      with the pulmonary embolism.
AB  - We evaluated electrocardiographic and echocardiographic changes of 40 patients
      with pulmonary thrombo-embolism proved by perfusion scintigrams. ECG-changes
      included sinus tachycardia or absolute tachyarrhythmia de novo, changes type
      Q1S3T3 and changes in right precordial leads. Analyses of echocardiography
      included hyperkinesis and then dilatation and apical hypokinesis of right
      ventricule and tricuspid regurgitation with maximal transvalvular gradients. We
      emphasize such a sensibility of echocardiographic changes in early estimation of
      pulmonary thrombo-embolism severity and necessity for echocardiography as early
      as possible in suspected patients.

PMID- 17177656
TI  - Azythromicin versus amoxicillin-clavulanate in the treatment of acute sinusitis
      in children.
AB  - In this prospective study we compared the efficiency of azithromycin and
      amoxicillin-clavulanate in treatment of acute sinusitis in children. Seventy
      patients were included in the age between 5 and 15 years. Beside ENT and
      pediatricians examination, nasal and throat smear on culture and antibiogram is
      taken from all the patients, as well as, X-ray of paranasal sinuses and
      laboratory findings, followed by check-up of nasal and throat smear and X-ray of
      paranasal sinuses. Azithromycin in single daily dose of 10 mg/kg during three
      days showed same efficiency as amoxicillin-clavulanate given three times per day
      in dose of 45 mg/kg during ten days.

PMID- 17177659
TI  - How much do we know about astigmatism?

PMID- 17177657
TI  - Efficacy in treatment of cervical HRHPV infection by combination of beta
      interferon, and herbal therapy in woman with different cervical lesions.
AB  - Cervical dysplasia, a premalignant lesion that can progress to cervical cancer,
      is caused primarily by a sexually transmitted infection with an oncogenic strain
      of the human papillomavirus (HPV). The HPV infections are treated through
      destroying the clinical lesions: laser, cryotherapy, podophyllin... The hope is
      that by causing local tissue inflammation that the body will be stimulated to
      mount an antibody response and thereby prevent recurrence. In contrast to other
      prevention approaches, vaccines can reduce susceptibility in uninfected partners
      by stimulating the immune system. Aloe vera has also been reported to retard
      tumour growth and stimulate the immune response to viruses. A list of possible
      actions of propolis includes: antibacterial, antifungal, antiviral, antioxidant,
      anticarcinogenic, antithrombotic and immunomodulatory. Research on the possible
      role of some B vitamins in preventing cancer began in the last few decades, but
      however this complex have an influence on immune status. The aim of our study is
      to try to treat the HPV infection as confirmed cause of neoplastic transformation
      with some herbal therapy and interferon and to try define the guidelines in the
      management of the HPV positive patients. Goal of this paper is to search for
      evidence of efficacy of any treatment for HPV infection of the cervix mostly in
      woman with no concomitant CIN. Fifty five woman affected by HPV genital infection
      were enrolled in the study from September 2005 to April 2006. Patients were
      classified according to the results of the HPV testing prior and after the
      therapy. Patients were randomized into two groups: the first group was HPV
      positive woman treated with other than recommended therapy (n=20), (control
      group); the second group was pharmacologically treated with intravaginal
      administration of an interferon and aloe vera-propolis in recommended scheme
      (n=35) with treatment of the possible fungal or bacterial genital infection prior
      to the specific therapy. The almost same therapy was recommended to the male
      partner. Patients from the second group used B complex during the therapy.
      Patients were retested for the HPV presence after three or six month from therapy
      depend of the presence bacterial or fungal genital coinfection. Three months
      after applied therapy HPV infection was still present in more than 90% of the
      patients in the first group. In the second group treated according to the
      recommended therapy scheme HPV infection disappeared in 71.42% of the patients
      after three months and in 100% of patients after six months. Samples of the
      cervical smear for the HPV analysis were being taken during routine gynecological
      examinations, by using sticks with cotton, taken from the Digene Specimen
      Collection Kit, from the whole surface of a portion, and by mild rotating moves
      from the outer cervical entrance. Our results suggest that the combination of
      interferon and herbal therapy with B complex is effective, atraumatic and simple
      non-surgical treatment of HPV infection. Since prospective efficacy trials will
      take several years to complete, considering alternative approaches is also
      worthwhile.

PMID- 17177661
TI  - The use of visual search to assess attention.
AB  - BACKGROUND: Under some conditions, the time required for a visual search
      increases with the number of elements to be searched. It has been suggested that
      the overall search time reflects the duration that attention is devoted to each
      element multiplied by the number of elements. On this basis, it has been proposed
      that visual search time can be used as a measure of attention capability in
      dyslexic readers. However, there is evidence to suggest that the search time
      reflects task difficulty rather than attentional factors. Many dyslexic readers
      suffer from various sensory deficits. These deficits would effectively increase
      task difficulty for these readers. Here we use computer simulations to
      investigate the potential effects of sensory deficits on visual search. METHOD:
      Visual search was modelled on a computer within the framework of signal detection
      theory as a matter of detecting a noisy signal from a series of noisy
      distractors. Sensory deficits were modelled as decreased discriminability.
      RESULTS: Consistent with previous observations, we find that discriminability,
      which decreases with the number of distractors, may have a substantial effect on
      the search time. With regard to the effects of sensory deficits, we find that
      under low discriminability conditions, small sensory deficits may cause
      pronounced increases in search time. CONCLUSION: The finding that small sensory
      deficits may cause pronounced increases in search time makes it specifically
      problematic to use visual search to test attention in individuals who suffer from
      sensory deficits. This applies particularly to dyslexic individuals, many of whom
      have been shown to suffer from visual deficiencies.

PMID- 17177660
TI  - A review of astigmatism and its possible genesis.
AB  - Astigmatism is a refractive condition encountered commonly in clinical practice.
      This review presents an overview of research that has been carried out examining
      various aspects of this refractive error. We examine the components of
      astigmatism and the research into the prevalence and natural course of astigmatic
      refractive errors throughout life. The prevalence of astigmatism in various
      ethnic groups and diseases and syndromes is also discussed. We highlight the
      extensive investigations that have been conducted into the possible aetiology of
      astigmatism, however, no single model or theory of the development of astigmatism
      has been proven conclusively. Theories of the development of astigmatism based on
      genetics, extraocular muscle tension, visual feedback and eyelid pressure are
      considered. Observations and evidence from the literature supporting and
      contradicting these hypotheses are presented. Recent advances in technology such
      as wavefront sensors and videokeratoscopes have led to an increased understanding
      of ocular astigmatism and with continued improvements in technology, our
      knowledge of astigmatism and its genesis should continue to grow.

PMID- 17177662
TI  - Corneal conjunctivalisation in long-standing contact lens wearers.
AB  - BACKGROUND: There are many contact lens-related ocular surface disorders. Some
      can damage the limbal region where stem cells are thought to be located in its
      basal cell layer. This damage can result in destruction and a deficiency of
      corneal stem cells. One important sign of this complication is corneal
      conjunctivalisation. The purpose of this study is to describe clinical
      characteristics of a series of long-standing contact lens (CL) wearers with
      corneal conjunctivalisation (CC). METHODS: In a one-year (March 2004 to March
      2005) retrospective unmasked study, 591 CL clinical histories (195 new patients
      and 396 review patients) were analysed. RESULTS: There were 24 eyes of 14 myopic
      patients (93 per cent women) with CC without a specific disease entity known to
      cause limbal stem cell deficiency (LSCD). Conjunctivalisation occurred in the
      inferior limbus of three eyes (12 per cent). Only four patients (28.6 per cent)
      reported previous ocular symptoms. All were myopic with a mean spherical
      equivalent of -8.80 +/- 5.00 (SD) dioptres (range from -1.75 to -21.50 D) and
      mean visual acuity 0.9 +/- 0.2 (range from 0.4 to 1.2). The mean years of CL wear
      was 17.6 +/- 8.5 (CI 95% 13.2 to 22; range six to 30). All were daily-wear
      patients with a mean daily-wear time of 12.5 +/- 1.8 hours per day (CI 95% 11.6
      to 13.4). CONCLUSION: Corneal conjunctivalisation is a contact lens-related
      complication in asymptomatic patients. Optometrists can play an important role in
      early diagnosis, education and management of these patients.

PMID- 17177663
TI  - SARS, avian flu, bioterror: infection control awareness for the optometrist.
AB  - The outbreak of severe acute respiratory syndrome (SARS) in 2003 alerted the
      world to the new face of pandemic disease: highly contagious and fatal infections
      for which no vaccines are available and current drugs are largely ineffective. As
      a practitioner providing primary care, the optometrist must be familiar with new
      and evolving infections present in today's society. Though they may be viewed as
      extreme events, scenarios such as the re-emergence of SARS, the affliction posed
      by the H5N1 strain of avian influenza and the threat of a bioterrorist attack
      have all been described. In the event that such events occur, there is the
      potential for the spread of some highly virulent, transmissible disease. This
      paper highlights these public health threats and discusses several areas that the
      optometrist may want to consider regarding infection control in an era in which a
      highly transmissible disease is being spread from person to person.

PMID- 17177664
TI  - The influence of accommodative insufficiency on reading.
AB  - BACKGROUND: It is not known how accommodative insufficiency influences reading
      performance. METHODS: Reading eye movements were recorded before and after
      treatment for accommodative insufficiency in 12 school children (eight to 16
      years). During the eight-week treatment period all subjects wore a +1.00 D
      addition when reading. RESULTS: Large variations in reading patterns were found.
      Despite successful accommodative treatment (p < 0.001), no correlation was found
      to suggest improved reading velocity. DISCUSSION: Three case reports will be
      presented and the implications discussed.

PMID- 17177665
TI  - The effect of mydriasis from phenylephrine on corneal shape.
AB  - PURPOSE: A previous study reported that pharmacologically-dilated pupils changed
      the corneal shape. Researchers used mydriatic agents with significant cycloplegic
      effect. The current study investigates the effect of mydriasis on corneal shape
      using phenylephrine alone, where phenylephrine has minimal effect on the
      accommodative system and whether corneal topography can be done after pupil
      dilation. METHODS: Forty-four young healthy subjects with one eye randomly
      selected for mydriasis were used in this study. Twenty-two received one drop of
      2.5% phenylephrine (group 1); the other 22 subjects had one drop of 0.4%
      benoxinate instilled prior to the application of 2.5% phenylephrine (group 2).
      They were matched for age and refractive error. Anterior chamber depth, pupil
      size and corneal parameters were compared before and after mydriasis. The corneal
      parameters included best-fit sphere (BFS), surface asymmetry index (SAI), surface
      regularity index (SRI) and the axial and tangential powers in the form of
      flattest and steepest powers, and in the form of M, J(0), and J(45) vector
      presentation. RESULTS: Group 1 and group 2 subjects had similar pre-mydriatic
      baseline ocular parameters. The mean (+/- SD) pupil dilation was 1.24 +/- 0.59 mm
      for group 1 and 1.80 +/- 0.95 mm for group 2. The dilation was significantly
      larger in group 2 (unpaired t-tests: t = 2.36, p = 0.02). There were no
      significant changes in corneal parameters from mydriasis in either group.
      CONCLUSIONS: Previous investigations used mydriatic agents, which affected not
      only the pupil size but also accommodation. The current study found that
      mydriasis from phenylephrine, with minimal effect on accommodation, did not
      result in significant corneal alteration, and corneal topography can be measured
      after pupil dilation with phenylephrine.

PMID- 17177666
TI  - Peripheral pigmentary iris cyst: evaluation and differential diagnosis.
AB  - Peripheral iris pigment epithelial cysts are benign lesions of the anterior
      segment. They are located at the iridociliary junction and can produce a
      localised distortion and/or displacement of the iris. Patients who have these
      lesions are usually asymptomatic and in the absence of a careful slitlamp
      examination will often remain undetected. The aetiology of these cysts is unknown
      and they tend to be unilateral and solitary in nature. The cyst walls are
      composed of iris pigment epithelium and the lumen contains clear fluid. Women are
      three times more likely to develop these cysts, which must be differentiated from
      malignancies of the iris or ciliary body. We report a case involving a peripheral
      pigmentary iris cyst and discuss methods of differentiating this benign lesion
      from serious ocular tumours.

PMID- 17177667
TI  - Posner-Schlossman syndrome (glaucomatocyclitic crisis).
AB  - Posner-Schlossman syndrome (PSS) or glaucomatocyclitic crisis is a rare,
      typically unilateral recurrent inflammatory ocular hypertensive disease in which
      diagnosis can be challenging. An acute elevation of intraocular pressure is
      accompanied by or followed within a few days by a mild, often symptomless uveal
      inflammation. The mild nature of the uveitis at presentation of the first attack
      may go undetected. Medical treatment is indicated to prevent pressure-related
      optic nerve damage and to reduce inflammation. This report details a patient with
      Posner-Schlossman syndrome whose unilateral pressure elevation was initially
      treated as acute angle-closure glaucoma. He subsequently had several episodes of
      increased pressure over a two-year period. Diagnostic difficulties in this case
      are discussed.

PMID- 17177669
TI  - Improvement of the diagnosis of allergy by using purified allergens.

PMID- 17177670
TI  - Why do patients with rhinitis report symptoms?

PMID- 17177671
TI  - Do skin prick and conjunctival provocation tests predict symptom severity in
      seasonal allergic rhinoconjunctivitis?
AB  - BACKGROUND: In the investigation of seasonal allergic rhinoconjunctivitis (SAR),
      quantitative skin and conjunctival allergen challenge tests are used to measure
      individual allergen sensitivity. These tests are reproducible and relate well to
      prevalence but their relationship to symptom severity is less well established.
      OBJECTIVE: We wished to determine if quantitative skin prick tests (QSPT) and
      conjunctival provocation tests (CPTs) using a single grass pollen allergen
      extract are reproducible and predict symptom severity in SAR. METHODS: We
      retrospectively analysed data from 91 participants in a previously published
      randomized placebo controlled study of low dosage allergen immunotherapy who were
      randomized to receive placebo treatment. We examined the relationship between pre
      seasonal QSPT, CPT and SAR symptoms. RESULTS: We found a high level of
      reproducibility when repeated measures were compared for both the QSPT (P <
      0.001) and the CPT (P < 0.001) and moderate correlation (0.49) between the
      standard skin prick test (SPT) and the QSPT (P < 0.001). We found weak negative
      correlation (-0.27) between the QSPT and the CPT (P < 0.001). We found no
      correlation between seasonal symptom, use of rescue medication or quality of life
      (QOL) scores and pre-seasonal QSPT or CPT. Conclusion In the assessment of
      seasonal rhinoconjunctivitis, quantitative skin and conjunctival allergen
      challenge tests are strongly reproducible, although there is no correlation
      between these tests and seasonal symptom, use of rescue medication or QOL scores.

PMID- 17177672
TI  - Peroxisome proliferator-activated receptor-gamma agonists as potential anti
      inflammatory agents in asthma and chronic obstructive pulmonary disease.
AB  - Inhaled corticosteroids are the most effective therapy for chronic persistent
      asthma and have a role in the treatment of chronic obstructive pulmonary disease
      (COPD). However, corticosteroids have reduced efficacy in some patients with
      asthma and fail to halt the progressive deterioration in lung function
      characteristic of COPD. Additional or alternative drug treatments to
      corticosteroids are required to improve control of inflammation in patients with
      therapy resistant airway disease. Peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) agonists have displayed potent anti-inflammatory properties in
      experimental models of asthma and other airway diseases and as a result have the
      potential to become an additional treatment for asthma and COPD. We review the
      evidence from these experimental models and their applicability to asthma and
      COPD and the requirements for future clinical and experimental research.

PMID- 17177673
TI  - Purified allergens vs. complete extract in the diagnosis of plane tree pollen
      allergy.
AB  - BACKGROUND: Plane tree pollen allergy is a clinical disorder affecting human
      population in cities of Europe, North America, South Africa, and Australia.
      OBJECTIVE: To compare IgE-reactivity of the natural and recombinant forms of two
      major plane allergens, Pla a 1 and Pla a 2, with the reactivity of Platanus
      acerifolia pollen extract. METHODS: Forty-seven patients with P. acerifolia
      allergy, 15 of them monosensitized, and 24 control subjects were included in the
      study. Natural Pla a 1 and Pla a 2 were purified by standard chromatographic
      methods and recombinant proteins were expressed in Escherichia coli. Skin prick
      test and determination of specific IgE were performed with commercial P.
      acerifolia extract and natural and recombinant purified allergens. RESULTS: Pla a
      1 and Pla a 2 were responsible for 79% of the IgE-binding capacity against P.
      acerifolia pollen extract. A high correlation has been found between the IgE
      response to nPla a 1 (R = 0.80; P < 0.001) or nPla a 2 (R = 0.79; P < 0.001) vs.
      P. acerifolia extract as well as between natural and recombinant Pla a 1 (R =
      0.89; P < 0.001). Skin testing showed no significant differences between extract
      and nPla a 2, whereas a higher reactivity was found with nPla a 1. In contrast,
      rPla a 1 revealed markedly reduced sensitivity in comparison with extract by skin
      prick test and specific IgE. The sensitivity of the mix Pla a 1+Pla a 2 was 100%
      and 87.5% for monosensitized and polysensitized patients, respectively, with no
      false-positive reactions detected. Conclusion Pla a 1 and Pla 2 are sufficient
      for a reliable diagnosis of P. acerifolia in most patients and induce comparable
      skin test reactivity as a whole extract.

PMID- 17177674
TI  - Alternaria alternata NADP-dependent mannitol dehydrogenase is an important fungal
      allergen.
AB  - BACKGROUND: Alternaria alternata is one of the most important allergenic fungi
      worldwide. Mannitol dehydrogenase (MtDH) has previously been shown to be a major
      allergen of Cladosporium herbarum and cross-reactivity has been demonstrated for
      several fungal allergens. OBJECTIVE: The present study's objective was to clone
      the MtDH from an A. alternata cDNA library, express and purify the recombinant
      non-fusion protein and test its IgE-binding properties. Methods A cDNA library
      prepared from A. alternata hyphae and spores was screened for mannitol
      dehydrogenase by DNA hybridization with the radioactively labelled C. herbarum
      homologue as a probe. The resulting clone was sequenced and heterologously
      expressed in Escherichia coli as a recombinant non-fusion protein, which was
      purified to homogeneity and analysed for its IgE-binding capacity. RESULTS: The
      coding sequence of the full-length cDNA clone comprises 798 bp encoding a protein
      with a molecular mass of 28.6 kDa and a predicted pI of 5.88. Protein sequence
      analysis revealed an identity of 75% and a homology of 86% between the MtDHs of
      A. alternata and C. herbarum. The functional mannitol dehydrogenase was expressed
      in the E. coli strain BL21(DE3) transformed with the vector pMW172 and purified
      to homogeneity. The enzyme catalyses the NADPH-dependent conversion of d-fructose
      to d-mannitol. In IgE-ELISA and immunoblots, MtDH is recognized by 41% of A.
      alternata-allergic patients. In vivo immunoreactivity of the recombinant MtDH was
      verified by skin prick testing. Finally, inhibition-ELISA experiments confirmed
      cross-reactivity between the MtDHs of A. alternata and C. herbarum. CONCLUSION:
      Mannitol dehydrogenase (Alt a 8) represents an important new allergen of the
      ascomycete A. alternata that might be suitable for improving diagnostic and
      therapeutic procedures.

PMID- 17177675
TI  - Repeated measurements of mite and pet allergen levels in house dust over a time
      period of 8 years.
AB  - BACKGROUND: Studies of the association between indoor allergen exposure and the
      development of allergic diseases have often measured allergen exposure at one
      point in time. OBJECTIVE: We investigated the variability of house dust mite (Der
      p 1, Der f 1) and cat (Fel d 1) allergen in Dutch homes over a period of 8 years.
      METHODS: Data were obtained in the Dutch PIAMA birth cohort study. Dust from the
      child's mattress, the parents' mattress and the living room floor was collected
      at four points in time, when the child was 3 months, 4, 6 and 8 years old. Dust
      samples were analysed for Der p 1, Der f 1 and Fel d 1 by sandwich enzyme immuno
      assay. RESULTS: Mite allergen concentrations for the child's mattress, the
      parents' mattress and the living room floor were moderately correlated between
      time-points. Agreement was better for cat allergen. For Der p 1 and Der f 1 on
      the child's mattress, the within-home variance was close to or smaller than the
      between-home variance in most cases. For Fel d 1, the within-home variance was
      almost always smaller than the between-home variance. Results were similar for
      allergen levels expressed per gram of dust and allergen levels expressed per
      square metre of the sampled surface. Variance ratios were smaller when samples
      were taken at shorter time intervals than at longer time intervals. CONCLUSION:
      Over a period of 4 years, mite and cat allergens measured in house dust are
      sufficiently stable to use single measurements with confidence in epidemiological
      studies. The within-home variance was larger when samples were taken 8 years
      apart so that over such long periods, repetition of sampling is recommended.

PMID- 17177676
TI  - Skin test results and self-reported symptom severity in allergic rhinitis: The
      role of psychological factors.
AB  - BACKGROUND: In allergic conditions, the degree of skin test reactivity does not
      always correlate with the severity of clinical symptoms. Additional factors may
      contribute to the reported symptom severity. OBJECTIVES: To investigate the
      association between the magnitude of the skin prick test (SPT) response and the
      reported symptom severity in patients with allergic rhinitis and the possible
      modifying role of psychological factors. METHODS: One hundred four patients with
      allergic rhinitis and 23 with non-allergic rhinitis, classified according to
      their SPT response to 19 aeroallergens, were asked to rate the severity of five
      symptoms and to indicate whether their symptoms intensified on exposure to five
      common aeroallergens. They also completed a psychological questionnaire. Results
      Reported symptom severity of allergic rhinitis did not correlate with weal size
      for any of the aeroallergens tested or with the number of positive responses on
      SPT. It was not related to patient age, sex, or education. The reported symptoms
      severity correlated positively (0.29, P < 0.01) with reported symptom
      intensification on exposure to allergens. Moreover, both outcomes were positively
      associated with the psychological factors of hypochondriasis (0.20, P < 0.05 and
      0.18, P < 0.05, respectively), and somatic awareness (0.24, P < 0.05 and 0.33, P
      < 0.01, respectively), but not with neuroticism. CONCLUSIONS: The severity of
      symptoms experienced by patients with allergic rhinitis is apparently not related
      to the magnitude of SPT response, but rather to psychological factors of
      hypochondriasis and somatic awareness. Physicians should be aware of the
      contribution of psychological factors to patient perceptions of the intensity of
      symptoms and of the intensification of symptoms on their exposure to allergens.

PMID- 17177677
TI  - Allergen-specific helper T cell response in patients with cow's milk allergy:
      Simultaneous analysis of proliferation and cytokine production by
      carboxyfluorescein succinimidyl ester dilution assay.
AB  - BACKGROUND: The role of antigen-specific T cells in the allergic reaction to
      cow's milk or in tolerance induction is not yet fully understood. OBJECTIVE: This
      study was designed to analyse both cow's milk protein (CMP)-specific T cell
      proliferation and cytokine production simultaneously in children with cow's milk
      allergy (CMA) in comparison with subjects with various allergic backgrounds.
      METHODS: Carboxyfluorescein succinimidyl ester was used to detect cow's milk
      specific T cells by flow cytometry. The intra-cytoplasmic cytokine production of
      these antigen-specific T cells was also analysed. RESULTS: Significant
      differences of both CMP-specific CD4+ cell proliferation and cytokine production
      between CMA and non-allergic children were observed. While the proliferative
      responses of children who recently outgrew CMA were not significantly different
      from those of patients, the patterns of cytokine production were similar to those
      of non-allergic children. CONCLUSION: These results suggest that the presence of
      CMP-specific T cell clones per se does not produce CMA, but that the T-helper
      type 2-skewed pattern of those T cells is associated with adverse reactions.
      Although it is not possible to distinguish between individual patients with and
      without CMA on the basis of CFSE assays, these results contribute to the
      understanding of the pathogenesis and tolerance induction of CMA.

PMID- 17177678
TI  - Inhibition of human allergic T-helper type 2 immune responses by induced
      regulatory T cells requires the combination of interleukin-10-treated dendritic
      cells and transforming growth factor-beta for their induction.
AB  - BACKGROUND: In grass pollen-allergic individuals, T cell anergy can be induced by
      IL-10-treated dendritic cells (IL-10-DC) resulting in the suppression of T helper
      type 1 (Th1) as well as Th2 cells. This study was performed to analyse whether
      such IL-10-DC-treated T cells are able to act as regulatory T cells (Treg)
      suppressing the function of other T cells in the periphery. As transforming
      growth factor (TGF)-beta is also a potential inducer of Treg, we additionally
      analysed the inhibitory capacity of TGF-beta-treated T cells in this system.
      MATERIALS AND METHODS: Freshly isolated CD4+ or CD4+ CD25- T cells from grass
      pollen-allergic donors were stimulated with autologous mature monocyte-derived
      allergen-pulsed DC in the presence or absence of T cells previously cultured with
      IL-10-DC- and/or TGF-beta. RESULTS: Anergic T cells induced by allergen-pulsed IL
      10-treated DC or allergen-pulsed DC and TGF-beta enhanced IL-10 production and
      strongly inhibited IFN-gamma production of freshly prepared peripheral CD4+ or
      CD4+ CD25- T cells while proliferation and Th2 cytokine production were only
      slightly reduced. The combination of allergen-pulsed IL-10-treated DC and TGF
      beta had an additional effect leading to a significant suppression also of Th2
      cytokine production and proliferation. Suppression was not antigen-specific and
      was mainly mediated by cell-to-cell contact and by the molecule-programmed death
      1 and only partially by CTLA-4, TGF-beta and IL-10. CONCLUSION: These data
      demonstrate that regulatory T cells that also suppress Th2 cytokine production
      are induced by two signals: TGF-beta and IL-10-DC. This is of importance for the
      regulation of allergic immune responses and might be exploited for future
      therapeutic strategies for allergic diseases.

PMID- 17177679
TI  - Alterations of the ocular surface epithelial mucins 1, 2, 4 and the tear
      functions in patients with atopic keratoconjunctivitis.
AB  - BACKGROUND: An increased understanding of the ocular surface alterations at the
      cellular level in the conjunctiva and the cornea, may help explain the
      pathogenesis and the subsequent clinical appearance of atopic ocular allergies,
      which may be potentially blinding. PURPOSE: To investigate MUC 1, 2 and 4
      alterations, tear function and the ocular surface disorder in patients with
      atopic keratoconjunctivitis. METHODS: Twenty-eight eyes of 14 atopic
      keratoconjunctivitis patients as well as 22 eyes of 11 age-and sex-matched normal
      subjects were studied. The subjects underwent corneal sensitivity measurements,
      Schirmer's test, tear film break-up time (BUT), fluorescein and Rose Bengal
      staining of the ocular surface, conjunctival impression cytology and brush
      cytology. Impression cytology samples underwent periodic acid-Schiff and
      immunohistochemical staining with MUC 1, 2 and 4 antibodies. Brush cytology
      specimens underwent evaluation for inflammatory cell numbers and quantitative
      real-time-PCR for MUC 1, 2 and 4 mRNA expression. Patient eyes with fluorescein
      and Rose Bengal scores greater than four points were regarded to have significant
      epithelial disease in this study. RESULTS: The mean corneal sensitivity and BUT
      values were significantly lower in atopic patients with significant epithelial
      disease, compared with patients with insignificant epithelial disease and
      controls (P < 0.01). Brush cytology specimens from patients with significant
      epithelial disease revealed significantly higher numbers of inflammatory cells (P
      < 0.01). Specimens from patient eyes showed positive staining for MUC 1, 2 and 4.
      MUC 1, 2 and 4 mRNA expressions were significantly higher in eyes with
      significant epithelial disease compared with eyes with insignificant epithelial
      disease and eyes of control subjects. CONCLUSION: Ocular surface inflammation,
      decline in corneal sensitivity, tear film instability, changes in conjunctival
      epithelial MUC 1, 2 and 4 mRNA expressions were thought to be important in the
      pathogenesis of atopic ocular surface disease.

PMID- 17177680
TI  - Surfactant protein D regulates chemotaxis and degranulation of human eosinophils.
AB  - The collectin surfactant protein D (SP-D) is an important component of the
      pulmonary innate host defence. Up to now, little is known about the regulation of
      eosinophil function by SP-D. Various murine models of pulmonary hypersensitivity
      suggest that SP-D may be a potent anti-allergic protein. We investigated the
      modulation of eosinophil chemotaxis and degranulation by human SP-D. SP-D
      markedly inhibited the chemotaxis of eosinophils triggered by eotaxin, a major
      tissue-derived CC-chemokine, as shown in a modified Boyden chamber assay. In
      addition, degranulation of ECP in response to Ca2+ ionophore, immobilized IgG and
      serum from allergic patients was inhibited by SP-D. In a fixed-cell enzyme linked
      immunosorbent assay and in flow cytometry, SP-D bound to eosinophils. This
      binding was saturable and was inhibited by the addition of maltose and
      ethylenediaminetetraacetic acid, suggesting the involvement of the carbohydrate
      recognition domain of SP-D. In addition, flow cytometry showed significant
      interaction of SP-D with CD32 (FcgammaII receptor) on eosinophils, which might
      explain the inhibitory effect of SP-D on the IgG and serum-triggered eosinophil
      cationic protein degranulation of eosinophils. Our data further support the
      concept of an anti-inflammatory function of SP-D in the lung of patients with
      allergic diseases.

PMID- 17177681
TI  - Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways
      hyper-reactivity.
AB  - BACKGROUND: IL-25, a novel member of the IL-17 cytokine family, promotes CD4+ T
      helper 2 lymphocyte-like (Th type-2) inflammatory responses in the lung. Although
      IL-25 up-regulates IL-13 in the lung, the contribution of this and other type 2
      cytokine signalling pathways to the induction and persistence of airways hyper
      reactivity (AHR) and allergic inflammation are unclear. OBJECTIVE: To determine
      the downstream factors employed by IL-25 to induce Th type-2 pulmonary
      inflammation and AHR. METHODS: IL-25 was delivered to the airways of BALB/c mice
      by intra-tracheal (i.t.) instillation and AHR and Th type-2 inflammatory
      responses were characterized in wild type (WT) and Th type-2-cytokine and 
      signalling pathway-deficient (-/-) mice. RESULTS: IL-25 treatment resulted in
      AHR, eosinophilic inflammation, mucus hypersecretion and a progressive increase
      in the production of Th type-2 cytokines in the lungs. Levels of arginase-I (arg
      I) and eotaxin were also elevated by IL-25 treatment. A significant reduction in
      AHR, and attenuation of mucus production was observed in IL-25-treated IL-13-/-,
      IL-4 receptor alpha (IL-4Ralpha-/-)- and signal-transducer-and-activator-of
      transcription-factor-6 (STAT6-/-)-deficient mice. AHR was also inhibited in IL-4(
      /-)- and IL-5/eotaxin(1)(-/-)- deficient mice treated with IL-25, however, mucus
      hypersecretion was not completely ablated. IL-25 promoted Th type-2 responses by
      directly acting on naive T cells. CONCLUSION: IL-25 potently (single dose)
      induces sustained AHR and acute pulmonary inflammation with eosinophilia. IL-25
      induced AHR is dependent on the production of Th type-2 cytokines, and removal of
      IL-13 and its signal transduction pathway prevents IL-25-induced airways
      inflammation and AHR. IL-25 potently induces inflammatory cascades that may
      exacerbate allergic airways inflammation by promoting Th type-2 cytokine
      responses in conjunction with the up-regulation of factors (eotaxin and arg-I)
      that can amplify inflammation associated with allergic disorders. Dysregulation
      in IL-25 production may predispose to features of allergic airways disease.

PMID- 17177682
TI  - Differential expression of monocyte CD163 in single- and dual-asthmatic
      responders during allergen-induced bronchoconstriction.
AB  - BACKGROUND: Mononuclear phagocytes play an important role in modulating
      inflammatory reactions in response to antigen challenge. OBJECTIVE: To
      investigate the regulation of CD163, a marker of anti-inflammatory macrophages,
      during Dermatophagoides pteronyssinus (Dp)-induced bronchoconstriction. METHODS:
      Among 110 Dp-sensitive patients who underwent bronchial challenge with Dp, there
      were 51 dual responders (DR), 32 single responders (SR) and 27 non-responders
      (NR). Monocyte expression of CD14 and CD163 was evaluated by flow cytometry.
      Exhaled NO (eNO) concentration was determined on-line using a chemiluminescence
      analyser. In 21 DR, nine SR and 13 NR-soluble CD163 in plasma was measured by
      ELISA before, 1, 8 and 24 h after the challenge. RESULTS: In DR, the baseline
      expression of monocyte CD163 and eNO were significantly greater than in SR and
      NR. A pattern of (1) decreased monocyte CD163 expression, (2) unchanged sCD163
      and (3) increased eNO in DR was contrasted by a pattern of (1) increased CD163
      expression, (2) increased sCD163 and (3) unchanged eNO in SR. During allergen
      challenge, the changes in monocyte CD163 expression and sCD163 inversely
      correlated with the changes in eNO. CONCLUSION: Both pro-inflammatory and anti
      inflammatory responses to allergen challenge are uniquely expressed among SR and
      DR.

PMID- 17177683
TI  - Analysis of the inducible nitric oxide synthase gene polymorphisms in Czech
      patients with atopic diseases.
AB  - BACKGROUND: Nitric oxide (NO) is an important mediator of physiologic processes
      in the airways; it plays a significant role in the regulation of the T helper
      type 1/type 2 balance and contributes to the development of atopic diseases.
      OBJECTIVE: We analysed several polymorphisms mainly in the promoter region of the
      inducible NO synthase (NOS2, iNOS) gene and investigated their associations with
      asthma and/or atopic phenotypes. METHODS: We performed a case-control study in
      994 subjects (661 patients with atopic disorders, with subgroups of 304 patients
      with allergic asthma, and 333 healthy individuals), matched for sex, living in
      the same geographical area. Screening for polymorphisms was performed by
      combination of PCR and direct sequencing analysis. RESULTS: We analysed 14
      nucleotide sequence variants, seven most common of which were typed in quite
      large groups of our asthmatic, atopic and control populations. None of these
      seven frequent polymorphisms was associated with the phenotype bronchial asthma
      or other atopic diseases. Nevertheless, three from six common promoter
      polymorphisms showed a significant relation to feather's positivity (P value from
      0.01 to 0.03) and the NOS2 608Leu variant was significantly associated with
      asthma severity [p(corr) = 0.0005; odds ratio (OR) = 5.00, 95% confidence
      interval (CI): 1.88-13.33]. In haplotype analysis, the most common -2447C/-1659C/
      1026G/-0.7del/-277A/Ser608 haplotype was associated with a lower risk of asthma
      when compared with the common haplotypes with frequency more than 5% (P = 0.01,
      p(corr) < 0.05; OR = 0.65, 95% CI: 0.56-0.77). CONCLUSION: Our findings suggest
      that inducible NOS can play a role in atopic disorders, and several polymorphisms
      in its gene may be important for asthma protection or susceptibility.

PMID- 17177684
TI  - Molecular fingerprinting of the intestinal microbiota of infants in whom atopic
      eczema was or was not developing.
AB  - BACKGROUND: The rise in atopic diseases has been linked to disturbances in the
      intestinal microbiota composition. OBJECTIVE: The purpose of this study was to
      investigate the intestinal microbiota composition in infants in whom atopic (IgE
      associated) eczema was or was not developing, using a molecular fingerprinting
      technique. METHODS: Within a prospective birth cohort study, fecal samples have
      been collected at the infant's age of 1 month. Within the context of this cohort,
      we conducted a nested case-control study comparing fecal samples of 26 infants
      who became sensitized and developed eczema within the first year of life with 52
      non-sensitized non-eczematous infants. The composition of the fecal samples was
      examined using PCR combined with denaturing gradient gel electrophoresis. Using
      real-time PCR, total bacterial counts and bifidobacterial counts were enumerated.
      RESULTS: Neither total bacterial profiles nor the type and proportion of
      bifidobacteria in the feces were associated with the development of atopic
      eczema. The similarity of bacterial profiles was low; mean similarity was
      approximately 33% in both infants with or without atopic eczema. The prevalence
      of one specific band in total bacterial profiles was significantly higher in
      infants with atopic eczema compared with controls (96% vs. 71%, P = 0.01).
      Identification of this band revealed that it represented Escherichia coli.
      CONCLUSION: Although no association was found between the development of IgE
      associated eczema and the dominant gut microbiota as a whole or with the
      bifdobacterial microbiota, the association with E. coli indicates that
      differences in gut microbiota do precede the development of atopy.

PMID- 17177686
TI  - Immunoglobulin constant heavy G chain genes as risk factors in childhood
      allergies.
AB  - BACKGROUND: Several candidate genes have been found to be associated with the
      inflammatory response of IgE-mediated allergy, so also the immunoglobulin
      constant heavy G chain (IGHG) genes. The IGHG genes are situated close to the
      IGHE gene on chromosome 14q32, 5'mu, delta, gamma3, gamma1, alpha1, gamma2,
      gamma4, epsilon, alpha2, 3'. They are inherited in a Mendelian fashion and
      expressed randomly in allelic exclusion. The alternative and functionally
      different gamma3, gamma1 and gamma2 gene variants are found in four IGHG
      haplotypes, coding four B cell variants. OBJECTIVE: The aim of this study was to
      assess the frequency of different IGHG genes in relation to phenotypes associated
      with allergy, in a case-control study. METHODS: We identified the constant heavy
      chain genes of IgG in 198 allergic and non-allergic children participating in the
      Phase II of the International Study of Asthma and Allergy in Children. The IGHG
      genes were assessed by the alternative serum IgG subclass allotypes expressing
      the alternative alleles of gamma3, gamma1 and gamma2 genes, using ELISA and
      double immunodiffusion. RESULTS: The IGHG*bfn haplotype (=B1 cells) and IGHG2*n
      allele dominated (51% vs. 24%, P=0.002) and the IGHG*bf-n haplotype (=B2 cells)
      was infrequent (16% vs. 52%, P < 0.001) in allergic children with a family
      history of allergy, clinical manifest allergy and positive skin prick test (SPT).
      The frequency of IGHG genes was similar in children with maternal and paternal
      heredity and in children with wheezing, eczema or rhinitis, as well as in
      children with different positive SPT. The IGHG*bfn haplotype with the IGHG2*n
      allele was strongly associated with heredity for allergy. The IGHG*bf-n haplotype
      was inversely related to allergy. Conclusions IgG allotypes, immunochemical and
      functional variants of IgG molecules from IGHG genes are associated with atopy.
      The IGHG*bfn haplotype (=B1 cells) with the IGHG2*n allele dominates, associated
      with an increased risk for atopy. In contrast, the IGHG*bf-n haplotype (=B2
      cells) with the IGHG2*-n allele is associated with low risk.

PMID- 17177685
TI  - Cytokines and soluble CD14 in breast milk in relation with atopic manifestations
      in mother and infant (KOALA Study).
AB  - BACKGROUND: Conflicting evidence exists concerning the protective role of
      breastfeeding in allergy and atopic disease aetiology. Breast milk contains
      biologically active molecules influencing the innate immune system of newborns.
      OBJECTIVE: We aim to assess whether cytokines (TGF-beta1, IL-10 and IL-12) and
      soluble CD14 (sCD14) in breast milk are influenced by maternal atopic
      constitution and modify the development of atopic manifestations in infants.
      METHODS: Milk samples were collected at 1 month post-partum of 315 lactating
      mothers participating in the ongoing KOALA Birth Cohort Study. The cytokines and
      sCD14 were analysed by ELISA in the aqueous fraction. We compared the
      concentrations of cytokines and sCD14 in breast milk between mothers with and
      without an allergic history and also with and without allergic sensitization
      (specific IgE). Associations of cytokines and sCD14 with the development of
      eczema, wheezing in the first 2 years of life and allergic sensitization of
      infants at the age of 2 years were analysed by multivariate logistic regression
      analyses to correct for confounders. RESULTS: We found higher sCD14 levels in
      mothers with a positive vs. negative allergic history (7.6 vs. 7.0 microg/mL; P =
      0.04) and in mothers who were sensitized vs. non-sensitized (7.8 vs. 7.1
      microg/mL; P = 0.03). None of the studied immune factors were associated with
      infant's atopic outcomes. IL-10 was not detected above the detection limit of 0.2
      pg/mL. CONCLUSION: Taking together the results of the present and previous
      studies, we conclude that there is no convincing evidence for a relation between
      TGF-beta1, sCD14, IL-10 or IL-12 in breast milk and atopic manifestations in
      infants.

PMID- 17177687
TI  - Does animal breeding and conservation need new regulations for the exchange and
      use of genetic material?

PMID- 17177689
TI  - Impact of dominance effects on sow longevity.
AB  - The purpose of the current study was to estimate variance components, especially
      dominance genetic variation, for overall leg action, length of productive life
      and sow stayability until third and fifth parity in the Finnish pig populations.
      The variance components were estimated in two purebred [Landrace (LR), n = 23 602
      and Large White (LW), n =22 984] and crossbred (LR x LW, n = 17 440) data sets.
      Five different analyses were carried out for all the traits to compare the effect
      of sows' inbreeding, common litter environment and parental dominance in the
      statistical model when determining the genetic correlations of the traits for the
      two purebred and crossbred populations. Estimated heritabilities for the traits
      ranged from 0.04 to 0.06. The estimates for the proportion of dominance variance
      of phenotypic variance (d(2)) varied between 0.01 and 0.17, and was highest in
      the crossbred dataset. The genetic correlations of the same traits in purebred
      and crossbred were all high (>0.75). Based on current results, the effect of
      dominance should be accounted for in the breeding value estimation of sow
      longevity, especially when data from crossbred animals are included in the
      analyses. Because dominance genetic variation for sow longevity exists that
      variation should be utilized through planned matings in producing sows for
      commercial production.

PMID- 17177690
TI  - Effect of selection for growth on normal and reduced protein diets on weight
      gain, feed intake, feed efficiency and body composition in mice.
AB  - Mice selected for weight gain from 3 to 9 weeks of age on a normal (N) protein
      diet containing 19.3% protein and a reduced (R) protein diet with 5.1% protein
      were reared on both diets in generations 7 and 9. The lines NH, NC, NL, RH, RC
      and RL (H, high; C, control; L, low) were tested for weight gain on diet N and R
      and for feed intake and feed efficiency on diet N in generation 7. In generation
      9, the lines were tested for body composition traits (fat, protein and water
      percentage) at 3, 6, 9 and 12 weeks of age on both diets. A significant (p <
      0.0001) genotype x environment interaction for growth rate was observed in
      generation 7. Weight gain at both the protein levels was best improved by
      selection at the protein level itself. Furthermore, the ranking of the lines on
      diet N was similar for weight gain, feed intake and feed efficiency. In
      generation 9 at 9 weeks of age, the ranking of the lines for fat percentage was
      equal to the ranking for weight gain in generation 7 on both test-diets. The
      association between weight gain and protein or water percentage was less
      pronounced, particularly on diet R. These results suggest that the largest
      genetic improvement in growth rate is obtained when the protein content of the
      feed is the same in selection and production. However, when selection is carried
      out in one environment while the animals have to perform under conditions with
      varying nutrient protein contents, selection in an inferior environment may be
      advantageous.

PMID- 17177691
TI  - Factor analysis of body measurements in Arabian horses.
AB  - Data of 13 body measurements have been analysed from 166 Arabian horses, 123
      mares and 43 stallions, ranging from 49 to 298 months of age, belonging to
      Alzahraa stud, Cairo, Egypt. General linear model was used to study age and
      gender effects on these measures. Gender was a significant source of variation
      for most studied traits, but not for neck girth, cannon bone circumference of
      fore and hind legs, and pastern girth of fore and hind legs. Age significantly
      affected pastern girths of fore and hind legs and cannon bone circumference of
      fore legs, while there was no significant effect on the other measurements.
      Pearson correlations, adjusted for age effect, between measurements were
      estimated and ranged from 0.02 to 0.84 for mares and from -0.05 to 0.90 for
      stallions. Factor analysis with promax rotation for each gender was carried out
      to derive fewer independent common factors. Three factors were extracted which
      accounted for 66% and 67% of the total variance in mares and stallions
      respectively. The first, second and third factors in mares tended to describe
      body thickness, leg thickness and general size respectively; whereas in stallions
      they tended to differentiate among general size, leg thickness and body thickness
      respectively. The three extracted factors for each gender determine the main
      sources of shared variability that control body conformation in Arabian horses.
      These factors could be considered in selection programmes to acquire highly
      coordinated bodies in pure Arabian horses with fewer measurements.

PMID- 17177692
TI  - Associations of leptin gene polymorphisms with production traits in pigs.
AB  - The associations of leptin (LEP) gene polymorphisms C798T, T2411C, T3266G and
      T3469C with production traits were investigated in a F2 pig population produced
      by divergent crosses. The statistical model included genotype, sex, batch and
      genotype by sex interaction as fixed effects and sire as random effect.
      Polymorphism C798T was associated with variation in total teat number (p < 0.02)
      and left teat number (p < 0.03), and polymorphism T3469C was associated with
      weight at 21 days (p < 0.03), 42 days (p < 0.05), 63 days (p < 0.02) and 77 days
      of age (p < 0.04) as well as feed intake (p < 0.01), average daily gain (p <
      0.01), feed conversion (p < 0.01), bacon depth (p < 0.03) and slaughter weight (p
      < 0.03). Phenotypic associations were also performed by combining T3469C and
      C798T genotypes. Interaction between C798T genotypes and sex was observed for
      some traits. LEP genotypes had significant influence on performance traits, and
      can be considered as potential genetic markers for selection. However, these
      results have to be validated in commercial herds.

PMID- 17177693
TI  - Haplotype analysis of beta-actin gene for its association with sperm quality and
      boar fertility.
AB  - beta-actin (ACTB) was examined as a direct functional candidate gene for the
      possible association with sperm concentration, motility (MOT), semen volume per
      ejaculate, plasma droplet rate, abnormal sperm rate (ASR) and the fertility
      traits, non-return rate and number of piglets born alive (NBA). Three
      polymorphisms in intron 3 (T>C) and one polymorphism in exon 4 (T>C) of porcine
      ACTB gene were identified by comparative sequencing of animals of the breeds
      Pietrain and Hampshire. Association analysis revealed that haplotypes affected
      the variation of the traits MOT, ASR and NBA. The beneficial haplotypes may
      provide considerable improvement of sperm quality and fertility in the tested
      commercial boar population.

PMID- 17177694
TI  - Characterization of a line of pigs previously selected for increased litter size
      for RBP4 and follistatin.
AB  - The objective of this study was to determine if selection response for increased
      litter size in pigs could be partially attributed to three type 1 marker loci
      coding for genes known to affect litter size: oestrogen receptor (ESR), retinol
      binding protein 4 (RBP4) and follistatin (FS). In the high litter size line (LS),
      pigs from the largest litters, based on number of pigs born alive (NBA), were
      retained to parent the next generation. A randomly selected control line (LC) was
      maintained. Gilts were reared in litters of 10 pigs or less to minimize maternal
      effects. Pigs were measured at generations 10-12. Additional traits scored were
      number of fully formed pigs (NFF) and number of mummified fetuses (MUM). Breeding
      values for NFF and NBA were greater (p < 0.05) in LS than LC in generations 11
      and 12, but no significant line differences were found for MUM. The A allele of
      the ESR locus was fixed in both lines. After adjustment for effects of genetic
      drift, frequency of the two alleles segregating for the FS and RBP4 loci did not
      differ significantly between lines. No significant additive or dominance effects
      of the FS markers were detected for NFF, NBA and MUM in either LS or LC. Response
      to selection for increased litter size could not be attributed to effects at the
      ESR, RBP4 or FS loci.

PMID- 17177695
TI  - Heritability of hair whorl position on the forehead in Konik horses.
AB  - There are studies on the relationship between the position and shape of hair
      whorls on bovine forehead and phenotypic traits. According to anecdotal beliefs
      by horse users and handlers, temperamental traits may be related to the position
      of hair whorls in horses. No previous research on the mechanisms of inheritance
      of hair whorls has been performed, so the aim of the present study was to
      determine the heritability of the position of the hair whorl on the forehead of
      Konik horses. The horses (n = 362) were classified into five groups based on the
      whorl position on forehead with respect to the top and bottom eye lines. The
      estimated heritability of hair whorl position was 0.753 (SE = 0.056).
      Heritability adjusted for the discontinuity of the trait was 0.836. The results
      show that hair whorl position in Konik Polski horses is highly heritable. The
      possible relationship between position of hair whorls on the forehead and other
      morphological traits needs further research and should be interpreted with
      caution.

PMID- 17177696
TI  - A lost Sorraia maternal lineage found in the Lusitano horse breed.
AB  - A common female founder individual of the Portuguese horse breeds Sorraia and
      Lusitano was found while conducting research on the variation of the Lusitano
      mitochondrial DNA lineages in relation to studbook information. We obtained 416
      bp control region sequences from 16 descendents of a female Sorraia founder
      (Pomba) still represented in the living population of the Lusitano, according to
      the most recent edition of this breed's studbook. The same haplotype was found
      for all analysed samples and belongs to the haplogroup described by several
      authors as having predominantly Iberian, South American and North African
      haplotypes bringing new insights on the relationship between the Sorraia and the
      other Iberian breeds. This work illustrates how weak the boundary of breed
      establishment can be, especially at the same geographical region. Using the same
      founders in different breeds is surely one of the explanations to frequently
      shared haplotypes among recent breeds, resulting in a lack of consistency between
      mtDNA sequences and breeds and/or geographical regions.

PMID- 17177697
TI  - Molecular and cytogenetic paternity testing of a male offspring of a hinny.
AB  - An alleged male foal of a female mule, whose sire and grandparents were unknown,
      was identified for its pedigree. Parentage testing was conducted by comparing
      polymorphism of 12 microsatellite DNA sites and mitochondrial D-loop sequences of
      the male foal and the female mule. Both the sequence analysis of species-specific
      DNA fragments and a cytogenetic analysis were performed to identify the species
      of the foal and its parents. The results showed that the alleged female mule is
      actually a hinny, and the male foal, which possesses 62 chromosomes, qualifies as
      an offspring of the female hinny and a jack donkey.

PMID- 17177698
TI  - Application of bovine microsatellite markers for genetic diversity analysis of
      European bison (Bison bonasus).
AB  - In this study, the cross-amplification of a commercial multiplex set of 11 cattle
      (Bos taurus) microsatellites was tested on a panel of 35 European bison (Bison
      bonasus) individuals. After polymerase chain reaction optimization, all loci
      cross-amplified successfully in investigated bisons. Number of alleles and
      observed and expected heterozygosity per locus are in the range of 2-4, 0.086
      0.629 and 0.288-0.621 respectively. The availability of a heterologous set of
      multiplexed microsatellite markers derived from cattle opens an avenue for
      collecting profound genetic data for efficient conservation management strategies
      of the European bison.

PMID- 17177699
TI  - Bos indicus type of growth hormone receptor gene is retained in Japanese Black
      cattle.
AB  - The growth hormone receptor (GHR) gene is responsible for growth and carcass
      traits, and polymorphisms associated with the variation of meat production are
      thought to occur in the liver-specific promoter of the GHR gene in cattle. The
      aim of this study was to analyse the structure of the liver-specific promoter of
      GHR in Japanese Black cattle, as the relationship between GHR polymorphism and
      meat production is poorly understood in this breed. Typically in European cattle,
      the LINE-1 element, a family of retrotransposons, is inserted in the liver
      specific promoter. However, a short GHR promoter without the LINE-1 sequence was
      found in the Japanese Black breed as in Bos indicus cattle. The frequency of the
      short allele was approximately 60%. In addition, 24 of 29 Holstein/Japanese Black
      crosses carried the short allele from their sire. The present result suggests
      that the short allele for GHR may be a candidate marker for improving meat
      production of Japanese Black cattle.

PMID- 17177700
TI  - Single nucleotide polymorphism identification, linkage and radiation hybrid
      mapping of the porcine pituitary adenylate cyclase-activating polypeptide type I
      receptor gene to chromosome 18.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with
      diverse biological actions. Type I PACAP receptors (PACAPR) are specific for
      PACAP, whereas type II and III PACAPRs are less restricted. To localize and
      analyse the variation of this gene, a 559-bp long intronic fragment of the
      porcine PACAPR gene was amplified by polymerase chain reaction and sequenced in
      samples from five different pig breeds. One single nucleotide polymorphism was
      identified and its allele frequency was determined in all five breeds. Linkage
      analysis in a Berkshire x Yorkshire reference family placed the PACAPR gene on
      chromosome 18, between SW787 and S0062 (SW787- 8.1 cM -PACAPR- 3.0 cM -S0062).
      Radiation hybrid mapping confirmed that the PACAPR gene was linked to SW1682 on
      chromosome 18 (28.8 cR(3000); LOD = 10.4).

PMID- 17177701
TI  - Information derived from sensitization test methods: test sensitivity, false
      positives and false negatives.
AB  - Predictive toxicology tests for the prospective identification of skin
      sensitizing chemicals are well known and have been used for many years. However,
      of these, only the local lymph node assay (LLNA) has actually undergone formal
      independent assessment to determine the accuracy of the predictions, particularly
      with respect to the likelihood of false positives and false negatives. Often,
      efforts to increase the sensitivity of a test (reducing false negatives) tend to
      increase the number of false positives. In this short review, these issues are
      discussed in particular relation to the 3 predictive tests available in
      regulatory toxicology, the guinea-pig maximization test, the occluded patch test
      of Buehler and the LLNA. A key perspective is that no predictive test is without
      limitations; having a good appreciation of these limitations is necessary for
      making the best use of the information derived from these methods.

PMID- 17177702
TI  - Allergic contact dermatitis from modified colophonium in wound dressings.
AB  - This study concerns a 69-year-old female patient with a longstanding history of
      venous ulcerations on both lower legs and multiple sensitivities, who developed
      eczematous lesions with the hydrocolloid dressing Combiderm (Convatec Ltd., a
      Bristol-Myers Squibb division, Ickenham, Middlesex, UK). Epicutaneous tests were
      positive to this dressing and to a modified colophonium derivative, i.e. glyceryl
      rosinate, however not to the unmodified colophonium from the standard series. A
      review of the literature showed several case reports about sensitization to
      similar hydrocolloids being distributed under various brand names in different
      countries and which contain the pentaerythritol ester of the hydrogenated rosin
      as the tackifying agent. Some of the patients described did, while others did
      not, react to colophonium but only to a modified derivative. In our patient, the
      reaction to glyceryl rosinate most probably represent cross-sensitivity with the
      modified colophonium derivative used in Combiderm, the presence (but not the
      exact nature) of which was showed by the company. In patients where allergic
      contact dermatitis from hydrocolloid dressings is strongly suspected and
      colophonium tests negatively, patch testing to modified colophonium derivatives
      should therefore be performed. As the complete composition of wound dressings is
      most often unknown, we urgently advocate legal requirements for labelling of
      those and in fact all medically used devices.

PMID- 17177703
TI  - Allergic contact sensitization in the general adult population: a population
      based study from Northern Norway.
AB  - Few studies have so far addressed the prevalence and risk factors for contact
      sensitization in the general adult population; however, many such studies have
      been conducted in hospitals. We present the prevalence of contact sensitization
      in a general adult population and its relationship to potential risk factors like
      smoking, ear piercing and atopic diseases. 1236 adults (44.2% men and 55.8%
      women) were randomly selected from a cross-section of the population in Sor
      Varanger municipality, Norway, and patch tested with TRUE Test (Pharmacia,
      Hillerod, Denmark). Contact sensitivity to at least 1 out of 24 allergens was
      found in 35.4% of the women and in 14.8% of the men. The most common allergens
      were nickel (17.6%), cobalt (2.8%), thiomersal (1.9%), fragrance mix (1.8%) and
      colophony (1.2%). All other allergens were observed in 1.0% or less. In women,
      ear piercing was an important risk factor for nickel sensitization. No such
      significant correlation was seen in men [in women relative risk (RR) = 3.30, 95%
      confidence interval (CI) = 2.01-5.43, and in men RR = 1.82, 95% CI = 0.66-5.00],
      and contact sensitivity was associated with atopic dermatitis (AD) [adjusted odds
      ratio (OR) = 1.58, 95% CI = 1.04-2.40] and smoking (adjusted OR = 1.42, 95% CI =
      1.01-1.99) in women but not in men. The prevalence of contact sensitivity was
      common in this general population, especially in women. Smoking and AD might be a
      risk factor for contact sensitization.

PMID- 17177704
TI  - Intervention implementation research: an exploratory study of reduction
      strategies for occupational contact dermatitis in the printing industry.
AB  - BACKGROUND: Occupational dermatitis is a problem in the printing industry but can
      be avoided through adequate protective measures. Research into intervention
      implementation is fundamental to the success of a formal intervention
      effectiveness trial. OBJECTIVES: The preliminary testing of four risk reduction
      strategies for occupationally caused dermatitis, which represent a range of
      approaches and cost implications. PATIENTS/METHODS: The strategies, the provision
      of (i) skin checks plus treatment advice; provision of (ii) gloves of the correct
      type/size plus use of an after-work cream; provision of (iii) information
      highlighting the problem of occupational dermatitis and (iv) development of a
      best practice skin care policy, were evaluated over 3 months in two non-randomly
      selected companies. A post-intervention evaluation into the effectiveness and
      efficacy of the intervention was also carried out. RESULTS AND CONCLUSIONS: All
      interventions were found to be acceptable to some extent. No single intervention
      appeared to be completely effective. The most practical intervention appeared to
      be the regular use of gloves of the correct type and size. This preliminary
      intervention study has demonstrated an improvement in the skin condition of
      workers examined and points towards the need for further testing of risk
      reduction strategies for the prevention of dermatitis in the printing industry on
      a much larger scale.

PMID- 17177705
TI  - Occupational autoeczematization or atopic eczema precipitated by occupational
      contact dermatitis?
AB  - Autoeczematization is characterized by the sudden dissemination of a previously
      localised form of eczema. While widely described, most cases reported have
      followed chronic, localized stasis dermatitis. In this study, we describe the
      clinical scenario of occupational contact dermatitis (OCD) triggering endogenous
      like eczema in atopic individuals, who often have not had eczema since childhood,
      if at all. These cases appear similar to previously described cases of
      autoeczematization. To show this clinical scenario, a series of 6 patients is
      presented from the Occupational Dermatology Clinic in Melbourne, Australia. These
      workers initially developed OCD, usually affecting the hands, which then
      precipitated a flare of more generalized eczema. This appeared clinically
      consistent with atopic eczema (AE), and often became recurrent, and sometimes
      persistent. OCD can precipitate a flare of more generalized eczema, in a pattern
      consistent with AE, which may then persist. The clinical scenario is similar to
      that described for autoeczematization. It is possible that the pathophysiology,
      when clarified, will prove to be similar. Workers' compensation issues may become
      complicated for these patients, as the relationship between their generalized
      eczema and their occupational exposures may not be readily apparent. As a result,
      the work relatedness of their condition may not be recognized.

PMID- 17177706
TI  - Is it possible to improve the patch-test diagnostics for isocyanates? A stability
      study of petrolatum preparations of diphenylmethane-4,4'-diisocyanate and
      polymeric diphenylmethane diisocyanate.
AB  - We have previously shown that the concentration of diphenylmethane-4,4'
      diisocyanate (4,4'-MDI) in commercial test preparations was so low that patch
      testing with the same was not reliable. The stability of 4,4'-MDI in petrolatum
      (pet.) was compared with pet. preparations of polymeric diphenylmethane
      diisocyanate (PMDI), which consists of a complex mixture of monomeric isomers and
      oligomers of MDI. Preparations of 4,4'-MDI and PMDI were stored under 3 different
      conditions, i.e. at room temperature, refrigerated and frozen. They were analysed
      continuously during 1 year with regard to the content of 4,4'-MDI, 3-ring
      oligomers and 4-ring oligomers using liquid chromatography-mass spectrometry.
      PMDI preparations kept frozen were stable for a year. All other preparations
      failed to fulfil the requirements of stability, i.e. +/-20% of the initial
      concentration. Storage in a freezer prolonged the lifetime for 4,4'-MDI. The
      decrease in concentration for preparations kept at room temperature and
      refrigerated was less rapid in PMDI preparations than in 4,4'-MDI preparations.
      PMDI preparations are better suited for patch testing patients exposed to MDI
      because they are more stable and homogeneous than 4,4'-MDI preparations. They
      better reflect possible allergens that workers are exposed to because products
      used in industry contain both monomers and oligomers.

PMID- 17177707
TI  - Patch test frequency to p-phenylenediamine: follow up over the last 6 years.
AB  - While the frequency of patch test reactivity to many cosmetic allergens has
      decreased over the last 20 years, we have previously shown that in our clinic,
      the patch test reactivity to p-phenylenediamine (PPD) has remained stubbornly
      high between 2.5% and 4.2% in the years when patch testing was performed with 1%
      PPD. Further retrospective analysis of the PPD patch test frequency over the last
      6 years shows an increasing rate of PPD patch test frequency, showing an upward
      linear trend. This increasing trend cannot be fully explained by any increase in
      patch testing of Southern Asian patients or of sensitization caused by PPD
      exposure from 'temporary henna tattoos'. An alternative explanation may be the
      increasing use of permanent hair dyes.

PMID- 17177708
TI  - Variation in the amount of petrolatum preparation applied at patch testing.
AB  - The elicitation of a positive patch test reaction in a given individual depends
      upon the dose of the sensitizer applied, the patch test technique and the
      occlusion time. The dose is determined by the concentration and volume/amount of
      test preparation applied. If the same amount/volume of a test preparation is
      applied all the time with the same test technique (same area of skin) and
      occlusion time, it is appropriate to use concentration as a dose parameter. Most
      contact sensitizers are incorporated in petrolatum (pet.). With pet. as vehicle,
      it is impossible to repeatedly apply an exact volume/amount. This study was
      performed to investigate the inter- and intra-individual variation of pet.
      preparation applied at patch testing by 3 technicians. Weighing demonstrated that
      the 3 technicians had about the same precision in their pet. application. The
      investigation demonstrates that there is both an inter-individual (statistically
      significant) and intra-individual variation in the amounts of pet. applied at
      patch testing for the 3 technicians. Presently, there is no recommendation on
      what amount of pet. preparation to apply, which merits a decision to be taken
      based on thorough investigations on the appropriate volumes of pet. preparation
      to be applied in various patch test systems.

PMID- 17177709
TI  - Occupational contact dermatitis from propolis in a dental technician.

PMID- 17177710
TI  - Allergic contact dermatitis to pimecrolimus.
AB  - Pimecrolimus suppresses the proinflammatory cytokine production of cutaneous T
      and mast cells (1). It is used to treat atopic dermatitis and is the active
      ingredient in the topical formulation pimecrolimus 1.0% cream (Elidel, Novartis
      Pharma AG, Basel, Switzerland).

PMID- 17177711
TI  - Occupational airborne contact dermatitis from omeprazole.

PMID- 17177712
TI  - Allergic contact dermatitis due to Zantedeschia aethiopica.

PMID- 17177713
TI  - Concomitant development of photoallergic contact dermatitis from ketoprofen and
      allergic contact dermatitis from menthol and rosin (colophony) in a compress.

PMID- 17177714
TI  - Octyl salicylate: a new contact sensitivity.
AB  - We describe acute contact sensitivity to octyl salicylate, an ultraviolet filter,
      used in many cosmetics and sunscreens.

PMID- 17177715
TI  - Concomitant allergic contact dermatitis due to Rosmarinus officinalis (rosemary)
      and Thymus vulgaris (thyme).

PMID- 17177716
TI  - Allergic contact dermatitis to cow's hair.
AB  - A 32-year-old farmer woman with delayed type of allergy to cow's hair is
      described in this study. She had the 5-year history of erythematous, desquamative
      lesions on the dorsal side of the hands and forearms. Shortly after entering the
      cowshed, she showed relapse of skin symptoms and total regression when she was
      away from the farm. The patch test to European standard series, hair of the cow
      from the patient's cowshed, hay, and stable hay was performed. Additionally,
      prick tests were performed on inhalant allergens such as hair of the cow from the
      patient's cowshed, hay, stable hay and cow's milk, total immunoglobulin class E
      (IgE) together and specific IgE to cow dander and milk. Patch test showed
      positive reaction to cow's hair, cobalt chloride, nickel sulfate, and thimerosal.
      All other tests were negative.

PMID- 17177717
TI  - Contact urticaria to olives.

PMID- 17177718
TI  - Allergic contact dermatitis due to levobunolol with cross-sensitivity to
      befunolol.

PMID- 17177719
TI  - Haptens, prohaptens and prehaptens, or electrophiles and proelectrophiles.
AB  - It is argued that the term 'hapten', and derived terms such as 'pro-hapten' and
      'pre-hapten' are ambiguous and unnecessary. It is proposed that their use be
      abandoned. Instead, when considering the chemical basis of skin sensitization, it
      is preferable to classify compounds according to the chemical reaction mechanisms
      by which they can modify proteins.

PMID- 17177723
TI  - Growing interest in the medical world in the topics of wound healing and tissue
      repair.

PMID- 17177720
TI  - Corticosteroid contact allergy--the importance of late readings and testing with
      corticosteroids used by the patients.

PMID- 17177725
TI  - Skin changes with aging and disease.
AB  - Skin undergoes numerous macroscopic changes during the aging process. These
      alterations in the skin result from both intrinsic changes to the cells and
      connective tissue of the skin that are inherent with the chronologic aging of the
      individual and changes as a result of environmental insults to the organ,
      particularly ultraviolet irradiation. The combination of these factors produces a
      tissue which possesses quite different attributes compared with the skin of a
      young individual and which may result in characteristic lesions, both malignant
      and benign. Understanding these changes and the underlying mechanisms for them
      will help to treat older individuals in whom specific lesions develop as well as
      help to prevent the occurrence of these pathologic conditions.

PMID- 17177726
TI  - Pressure ulcers in older persons: a preventive approach.
AB  - Strategies for the prevention of pressure ulcers are presented on the basis of
      the Agency for Health Care Policy and Research guidelines. A broad, holistic
      approach to care of the elderly, focusing on rehabilitative and restorative
      measures is introduced. Topics include the effects of bed rest and
      deconditioning, nutrition, and mobility issues. A broad approach to care,
      involving the expertise of multiple disciplines, is advocated.

PMID- 17177727
TI  - Biochemical analysis of acute and chronic wound environments.
AB  - The process of wound healing involves a complex interaction between numerous cell
      types, extracellular matrix molecules, and soluble mediators including growth
      factors and cytokines. This complex milieu is under active investigation for the
      purposes of beginning to understand how this environment regulates tissue repair.
      Quantitation of growth factors, cytokines, and matrix metalloproteinases within
      surgical wound fluids may help to elucidate this regulatory network, not only in
      noncomplicated wound healing but also in pathologic lesions such as chronic
      ulcers.

PMID- 17177728
TI  - Back to the future for wound care?
AB  - The European Renaissance was a time of enormous change and rapid progress in the
      arts, sciences, and medicine. A glimpse of wound care in the last phase of the
      European Renaissance is provided by the analysis of work by Wilhelm Fabry, the
      "father of German surgery," as provided in his book De Combustionibus ("Burns")
      which details his range of treatments for the burn wound, as well as his approach
      to the later problems of scarring and contracture. We describe some of the
      historic events which may have stimulated Fabry's writings, in particular, the
      influences passed down from the medical school of Padua which thereby advanced
      the cause of wound care and surgery. Finally, we briefly explore the potential of
      such an approach to the works of our medical forefathers.

PMID- 17177729
TI  - Interobserver agreement, sensitivity, and specificity of a "healed" chronic
      wound.
AB  - The primary end point of most wound healing studies is the clinically subjective
      evaluation of whether a wound is healed. Recently the Wound Healing Society
      proposed a definition of an acceptably healed wound. With the use of color
      transparencies of wounds with known clinical outcomes, the investigation
      presented here evaluated the reliability and validity of this definition as
      interpreted by 16 untrained observers. Interobserver reliability (Kappa
      statistic) was 0.68 (95% confidence interval: 0.66, 0.70), sensitivity 0.84
      (confidence interval: 0.81, 0.90), specificity 0.92 (confidence interval: 0.88,
      0.97), and positive predictive value 0.93 (confidence interval: 0.89, 0.97). We
      conclude that reliability and validity of judgments of wound healing are good
      using this definition of a healed wound, permitting its use in clinical
      investigations and routine clinical care.

PMID- 17177730
TI  - Centrally and locally mediated thermoregulatory responses alter subcutaneous
      oxygen tension.
AB  - Mild perianesthetic hypothermia decreases resistance to infections. Decreased
      resistance likely results in part from direct immune inhibition. However,
      decreased tissue oxygen partial pressure also decreases resistance to infection
      by impairing oxidative killing by neutrophils and collagen deposition.
      Thermoregulatory vasoconstriction decreases skin blood flow and may also decrease
      subcutaneous tissue oxygen tension. Accordingly, we determined the influence of
      centrally and locally mediated thermoregulatory vasomotion on subcutaneous oxygen
      tension. We also compared subcutaneous oxygen tension to other potential markers
      of tissue perfusion: laser Doppler flowmetry and transcutaneous oxygen tension.
      Arterial oxygen tension was maintained near 325 mm Hg in five volunteers. Control
      subcutaneous oxygen tension values were recorded after 1 hour of euthermia (no
      sweating or vasoconstriction). Volunteers were then cooled with a circulating
      water mattress positioned under the trunk and legs. After 1.5 hours of cooling
      sufficient to produce shivering, the right upper arm was covered for 1 hour with
      a small circulating water blanket set to 40 degrees C while systemic cooling
      continued. The volunteers were then systematically warmed to produce sweating,
      and the right arm was locally cooled. There was no correlation among laser
      Doppler flowmetry, transcutaneous oxygen tension, and subcutaneous oxygen
      tension. Systemic cooling significantly decreased subcutaneous oxygen tension,
      but subcutaneous oxygen tension in the right arm returned to control values
      during local heating. Systemic warming significantly increased subcutaneous
      oxygen tension, and 1 hour of local cooling failed to fully reverse the increase.
      These data indicate that thermoregulatory vasoconstriction significantly
      decreases tissue oxygen availability. Decreased subcutaneous oxygen tension may
      be one mechanism by which mild perianesthetic hypothermia facilitates development
      of surgical wound infections.

PMID- 17177731
TI  - Hyaluronic acid-dependent pericellular matrices in fetal fibroblasts: implication
      for scar-free wound repair.
AB  - Fetal fibroblasts are intrinsically different from postnatal fibroblasts. We
      studied the differences in expression, size, and assembly of pericellular
      matrices in human fetal and postnatal fibroblasts, as well as the effect of fetal
      fibroblast-conditioned media as a source of migration stimulating factor on
      pericellular matrix formation. Fibroblasts in their fifth to fifteenth passages
      were cultured for 24 hours before analysis. Streptomyces hyaluronidase (0.1
      U/ml), monoclonal mouse anti-human CD-44std, or anti-human CD-4 antibodies were
      added and incubated for 1 hour (at 4 degrees and 37 degrees C) before analysis of
      the pericellular matrices with the use of a particle exclusion technique. The
      pericellular matrix/cell body ratio of fetal fibroblasts was significantly larger
      than that of newborn (p < 0.002) and adult (p < 0.001) fibroblasts. Hyaluronidase
      disrupted the pericellular matrices in all three cell lines. Assembly of the
      pericellular matrices was blocked by anti-human CD-44std antibody but not by anti
      human CD-4 antibody at both 4 degrees and 37 degrees C. Incubation of fibroblast
      cell lines in fetal fibroblast-conditioned media did not increase pericellular
      matrix/cell body ratio but did increase the percentage of fibroblasts expressing
      a detectable pericellular matrix in adult (p < 0.01), newborn (p < 0.001), and
      fetal (p < 0.005) fibroblasts. We conclude that fibroblasts produce hyaluronic
      acid-dependent pericellular matrices which require interaction with a hyaluronic
      acid-binding protein for assembly. Large pericellular matrices are one intrinsic
      factor characterizing a unique fetal fibroblast phenotype.

PMID- 17177732
TI  - Enhancement of wound repair with a topically applied nitric oxide-releasing
      polymer.
AB  - Nitric oxide is an important cytotoxic agent for host defense which also
      regulates gene expression, signal transduction, and vasodilation. In normal
      wounds, nitric oxide synthesis and metabolism are significantly increased during
      inflammation and tissue remodeling. However, nitric oxide production is
      suppressed in wounds where healing is impaired by diabetes or steroid-treatment.
      Topical delivery of nitric oxide in therapeutic amounts may alleviate this
      deficiency and thereby enhance wound repair. Consequently, we developed
      polyethyleneimine cellulose NONOate polymer, a nonsoluble, nontoxic, polymer
      based NONOate--one of a new class of compounds that spontaneously release nitric
      oxide in a controlled fashion in aqueous media. Polyethyleneimine cellulose
      NONOate polymer was synthesized from polyethyleneimine cellulose to provide
      extended nitric oxide release with a half-life of 16 hours. Polyethyleneimine
      cellulose NONOate polymer or a control polymer was applied topically on full
      thickness dermal wounds of rats at the time of wounding and days 3, 7, 10, 14,
      17, and 21. Nitric oxide delivery was determined indirectly by measuring urinary
      nitrate. The first two polyethyleneimine cellulose NONOate polymer applications
      increased urinary nitrate output twofold to fourfold, whereas urinary nitrate
      output of control rats did not significantly increase. Nitrate output in
      polyethyleneimine cellulose NONOate polymer-treated rats was elevated compared
      with controls after each application, although this was attenuated in later
      applications. Rate of wound closure was measured with computer-based video
      imaging. Polyethyleneimine cellulose NONOate polymer-treated wounds were
      significantly smaller (p < 0.05) on days 7, 10, and 17 relative to controls,
      based on percentage of wound open relative to initial wound area. In a second
      experiment, telemetry-implanted rats were wounded to detect potential hypotensive
      effects as a result of polyethyleneimine cellulose NONOate polymer application.
      Topical polyethyleneimine cellulose NONOate polymer application to wounds showed
      no prolonged hypotensive effects, in contrast to a soluble NONOate which
      suppressed systolic blood pressure for over 6 hours. These results show that a
      nonsoluble, polymeric NONOate can provide topical nitric oxide delivery to wounds
      in a controlled manner, which may enhance wound healing. Further studies are in
      progress with other promising NONOate candidates to establish dose-response
      effects and therapeutic limits of exogenous nitric oxide release in impaired
      wound models.

PMID- 17177733
TI  - Alterations of angiotensin II receptor levels in full-thickness excisional wounds
      in rat skin.
AB  - Angiotensin II was recently shown to have a growth-promoting role after vascular
      injury and in the development of cardiac hypertrophy and fibrosis. In addition,
      angiotensin II may play a role in dermal wound repair. In this article,
      alterations in angiotensin II receptor levels in tissue harvested from full
      thickness excisional dermal wounds in adult Sprague-Dawley rats were examined. A
      2.25 cm(2) full-thickness excision of the dorsal skin was made under general
      anesthesia, and the tissue was harvested on days 1, 3, 5, 7, and 10 after
      wounding. The level of (125)I-Sar(1).IIe(8)-angiotensin II bound to membrane
      preparations of both granulation tissue and wound edge increased from day 1,
      peaked on day 5, and returned to nonsurgical levels by day 10. In both
      granulation and wound edge segments of the injured skin, the maximum binding on
      postoperative day 5 was about twice that of postoperative day 1 tissue or control
      skin. Competitive binding studies with angiotensin II type 1 receptor or type 2
      receptor antagonists (DuP 753 and CGP 42112B, respectively) showed that the
      receptors present in the healing dermal tissue from the adult rat were almost
      entirely of the type 1 receptor form.

PMID- 17177734
TI  - Negatively charged beads and transforming growth factor-beta1 stimulate bone
      repair in rabbits.
AB  - Previous studies have shown the osteogenic potential of negatively charged
      Sephadex beads when used to heal osseous defects in an animal model. The present
      study examined the effect of adding the growth factors transforming growth factor
      beta1 and basic fibroblast growth factor to negatively charged Sephadex beads and
      neutral (non-osteogenic) Sephadex beads in a critical size calvarial defect in
      rabbits. New Zealand White rabbits were divided into six groups of five rabbits;
      15 mm parietal defects were created and filled with either negatively charged
      Sephadex beads (three groups) or neutral Sephadex beads (three groups). Each
      group received either 2 microg of transforming growth factor-beta1, 1 microg of
      basic fibroblast growth factor, or buffer (control). Animals were killed at 5
      weeks, and their calvaria were submitted to plain radiographic and
      histomorphometric analyses. Defects treated with negatively charged Sephadex
      beads produced significantly more new trabecular bone than neutral Sephadex beads
      (p < 0.01), whereas the neutral beads treated with transforming growth factor
      beta1 formed significantly more bone than controls. The addition of transforming
      growth factor-beta1 to negatively charged beads resulted in near closure of the
      craniotomy defect. The application of transforming growth factor-beta1 to this
      model resulted in significantly more ectopic bone (p < 0.01) outside the defect
      on the dural and periosteal surfaces. Basic fibroblast growth factor, in the dose
      used, appeared to have an inhibitory effect on new bone formation fostered by
      negatively charged Sephadex beads. This study suggests that the addition of
      transforming growth factor-beta1 to the known osteoconductive matrix of
      negatively charged Sephadex beads may be therapeutically useful in nonhealing
      bony defects.

PMID- 17177735
TI  - Recombinant human bone morphogenetic proteins-2 and -4 induce several mesenchymal
      phenotypes in culture.
AB  - Bone morphogenetic protein has previously been shown to induce the formation of
      cartilage and bone in vivo. We have isolated a population of mesenchymal stem
      cells from rat skeletal muscle capable of forming multiple mesodermal
      morphologies in vitro. These cells were treated with recombinant human bone
      morphogenetic proteins-2 and -4 to determine the differentiation-inducing
      activities of bone morphogenetic protein on these cells. The mesenchymal stem
      cells were cultured in medium with 10% preselected horse serum containing 0 to
      100 ng/ml recombinant human bone morphogenetic proteins-2 or -4 for a maximum of
      4 weeks. Control cultures maintained the stellate morphology of mesenchymal stem
      cells. Cultures treated with recombinant human bone morphogenetic protein-2
      exhibited discrete cartilage nodules and mineralized bone nodules. The first
      increase in chondrogenesis was seen at 0.5 ng/ml. Cultures treated with
      recombinant human bone morphogenetic protein-4 also exhibited an increase in
      chondrogenesis at the higher concentration of 2 ng/ml. Skeletal myotubes and
      adipocytes also appeared in cultures treated with either bone morphogenetic
      protein. Mesenchymal stem cells do respond to inductive factors, but bone
      morphogenetic proteins-2 and -4 were not specific for the induction of cartilage
      and bone.

PMID- 17177736
TI  - Ischemia and reperfusion reduce the endogenous basic fibroblast growth factor in
      rat skeletal muscles: an immunohistochemical study.
AB  - Polyclonal antibodies directed against human recombinant basic fibroblast growth
      factor were used in immunohistochemical studies to localize this growth factor in
      normal and wounded rat skeletal muscles. According to the intensity of the stain,
      three main classes of fibers could be identified: the strongly, moderately, and
      weakly stained fibers. Basic fibroblast growth factor immunoreactivity was found
      mainly in the extracellular matrix, primarily in the endomysium, which includes
      the heparin-containing basal lamina, and also in the capillary basal membrane of
      both normal and wounded muscles; however, the signal intensity was much stronger
      in normal muscles. The distribution of basic fibroblast growth factor in wounded
      muscles became markedly heterogeneous and sparse. After 4 hours of ischemia,
      about 40% of skeletal muscle fibers lost their basic fibroblast growth factor
      immuno-reactivity. Muscles which underwent 4 hours of ischemia and 24 hours of
      reperfusion had only a diminished basic fibroblast growth factor
      immunoreactivity. The pathologic results supported the concept of destroyed cell
      connection and fiber necrosis in ischemic and reperfused muscles. Potential
      mechanisms involved in this reduced concentration of basic fibroblast growth
      factor in wounded muscles may include oxygen free radical activation, a
      generalized effect of the inflammatory response, and reduced secretion of
      endogenous basic fibroblast growth factor. These results are only partially
      compatible with the established mitogenic role of this growth factor and suggest
      that a reduction of endogenous fibroblast growth factor may partly contribute to
      a delay in wound healing.

PMID- 17177738
TI  - Development of a multilayered in vitro model for studying events associated with
      wound healing.
AB  - Simplified in vitro models such as cellular monolayer cultures have only limited
      usefulness in the study of cutaneous wound repair processes. This has stimulated
      the investigation of three-dimensional tissue equivalent systems such as the
      dermal and skin equivalent models. With the use of a wound system constructed of
      rat tail type I collagen and human dermal fibroblasts, experimental wounding was
      accompanied by problems with mechanical scoring of the plastic substratum which
      prevented cell migration. These problems were overcome with the use of a
      multilayered model in which a punch biopsy-wounded dermal equivalent (bilayered
      model) or skin equivalent (tri-layered model) was placed onto an acellular
      collagen lattice and fixed in place with polymerizing collagen. This model
      permitted observation of the process of cellular repopulation of the "wound
      space," into which both fibroblast and keratinocyte migration commenced within 1
      day. The number of fibroblasts in this space increased dramatically over a period
      of 9 days, the cells appearing to migrate both over and through the acellular
      lower collagen layer. Keratinocyte reepithelialization of the "wound space" was
      completed after 5 days. With the model it was shown that platelet-derived growth
      factor--AB and epidermal growth factor had positive effects in increasing
      fibroblast number within the wound space. In conclusion, the model described here
      should facilitate the study of fibroblast and keratinocyte responses to a wound
      stimulus in vitro and be a plausible in vitro system for evaluating agents which
      may have a potential stimulatory or inhibitory effect on numerous cellular
      responses associated with wound healing.

PMID- 17177737
TI  - Assessing wound severity with color and infrared imaging of reactive hyperemia.
AB  - This study examined the use of cutaneous reactive hyperemia as a means for
      noninvasive assessment of wound severity of newly formed temperature-modulated
      pressure injuries in a porcine model. Two methods to quantify the extent of the
      reactive hyperemic reflex were developed. First, color image analysis was used to
      measure the hue of injured tissue. The specific hue of the skin surface of the
      wounded site was found to provide an indication of the severity of the wounds.
      Second, infrared imaging, coupled with computer image processing, was used to
      detect differences in skin temperature. The relative surface temperature of the
      wounds showed a strong correlation with the presence or absence of deep tissue
      injury. Both techniques correlated with the severity of the injuries as
      determined by a histologic assessment of biopsied tissue, but infrared imaging
      provided the better means to assess wound depth.

PMID- 17177739
TI  - The facial rejuvenation algorithm.

PMID- 17177740
TI  - Hydroquinone and its analogues in dermatology - a risk-benefit viewpoint.
AB  - Hydroquinone (HQ) has been used since the 1950s in commercially available over
      the-counter skin lightener products and since the 1960s as a commercially
      available medical product. It is also used in cosmetic products such as hair dyes
      and products for coating finger nails. Beginning in 2001, HQ is no longer
      authorized for use in cosmetic skin lightening formulations in European Union
      countries, although products containing arbutin, an analogue of HQ, and
      botanicals, including plants that naturally contain HQ and arbutin, continue to
      remain available in European countries. The potential toxicity of HQ is dependent
      on the route of exposure, and toxicity in rodents is highly sex-, species-, and
      strain-specific. Subchronic and chronic toxicity in experimental animals is
      primarily limited to nephrotoxicity in male F-344 rats. Dermal toxicity studies,
      even those conducted in the sensitive male F-344 rat, are essentially devoid of
      systemic toxicity. Developmental and reproductive toxicity studies with HQ in
      rats and rabbits have not demonstrated significant effects. Cancer bioassay data
      for HQ demonstrate limited effects and are not sufficient to classify HQ for
      human carcinogenicity. Epidemiology and occupational studies of workers with
      extensive exposure to HQ have not reported any evidence of adverse systemic
      health effects or carcinogenicity. A risk-benefit approach is recommended for
      assessing the available data for HQ, arbutin, and other materials in use as, or
      proposed for use as, skin lighteners to provide optimal therapeutic benefits to
      patients with pigmentary changes of the skin.

PMID- 17177741
TI  - Laser removal of pigmented and vascular lesions.
AB  - Twenty years of laser dermatology has resulted in current technology which allows
      variable spot sizes, different wavelengths, and a variety of effective cooling
      devices. These developments have made the treatment of cutaneous pigmented and
      vascular lesions safe and efficacious by targeting selected chromophores while
      minimizing damage to the surrounding tissue. Vascular lesions are targeted by a
      variety of wavelength lasers including the KTP (532 nm), pulsed dye (585-595 nm),
      and the Nd:YAG (1064 nm) laser systems. Pigmented lesions may be treated with a
      wide variety of lasers due to the broad absorption spectrum of melanin. Intense
      pulsed light (IPL), with its widely adjustable parameters, has established itself
      as a useful adjunctive for the treatment of a variety of pigmented and vascular
      lesions. The purpose of this review article is to present the current treatment
      options for the common aesthetic complaints of pigmented and vascular lesions.

PMID- 17177742
TI  - Iron chelators may help prevent photoaging.
AB  - For years, cosmetic ingredients for anti-aging treatments have attracted
      consumers. Skin aging is accelerated by reactive oxygen species (ROS), generated
      by exposure to solar ultraviolet radiation (UVR), in a process known as
      photoaging. Because cutaneous iron catalyses ROS generation, it is thought to
      play a key role in photoaging. Iron is essential to almost all forms of life.
      However, excess iron is potentially toxic as its catalytic activity induces the
      generation of ROS. Iron-catalysed ROS generation is involved in numerous
      pathological conditions, including cutaneous damage. When skin is directly
      exposed to UVR, cutaneous intracellular catalytic iron levels increase because of
      the release of iron from iron-binding proteins such as ferritin. Consequently,
      the subsequent ROS generation may overwhelm cutaneous defense systems such as the
      cellular iron sequestration and ROS scavenging capacity. The harmful role of
      excess cutaneous iron implies that there may be a potential for topical iron
      chelator treatments. We now consider cutaneous photodamage skin photoaging as the
      result of iron-catalysed ROS generation and discuss preventative strategies based
      on iron chelators.

PMID- 17177743
TI  - Clinical experience and safety using phosphatidylcholine injections for the
      localized reduction of subcutaneous fat: a multicentre, retrospective UK study.
AB  - BACKGROUND: Phosphatidylcholine has been in safe use for over 30 years.
      Subcutaneous injections of phosphatidylcholine have now become used
      internationally for localized subcutaneous fat reduction on the face and body,
      but concerns about the safety of this treatment have arisen. AIMS: To assess
      retrospectively treatment outcomes and adverse effects associated with
      subcutaneous phosphatidylcholine use. PATIENTS AND METHODS: Thirty-nine UK
      doctors specifically trained and experienced in this treatment completed
      questionnaires, focusing on outcome and adverse effects experienced by patients.
      RESULTS: Ten thousand five hundred and eighty-one treatments had been
      administered over a mean duration of 13.1 months. Localized adverse effects
      (swelling, erythema, burning/stinging, pain, tenderness and bruising) were
      described by most patients as "very mild' (18.4%) or "mild" (39.2%). The total
      incidence of systemic side-effects was 3%: diarrhoea, nausea, dizziness/light
      headedness and intermenstrual bleeding were described by most patients as "very
      mild" (36%) or "mild" (55%). Only 15 (0.14%) "unexpected, unusually severe or
      prolonged" adverse reactions (commonly pain and/or swelling) were reported. These
      were all self-limiting and none were judged as serious. 73.8% of patients were
      either "very satisfied" or "satisfied" with treatment. CONCLUSIONS: This
      treatment appears to be associated with minimal risks when used by specifically
      trained and experienced doctors. The possible risks associated with this
      treatment should be balanced against the risks of other treatment options.

PMID- 17177744
TI  - Skin tolerance, efficacy, and quality of life of patients with red facial skin
      using a skin care regimen containing Licochalcone A.
AB  - BACKGROUND: Patients with rosacea and red facial skin often show sensitivity to
      skin care products which can exacerbate inflammation and subjective irritation.
      Besides pharmacologic management, special skin care is prudent to avoid
      cosmetically induced irritation and address cosmetic concerns. Appropriate skin
      care should provide gentle cleansing, UVA/UVB protection, effective
      moisturization, and concealing pigments to neutralize the appearance of redness.
      AIMS: To evaluate skin compatibility and efficacy of a skin care regimen
      containing licochalcone A (Lic A), an anti-irritant from the licorice plant
      Glycyrrhiza inflata, for subjects with mild to moderate facial redness.
      PATIENTS/METHODS: Sixty-two patients with mild to moderate red facial skin used a
      four-product skin care regimen for 8 weeks. Clinical assessments of erythema and
      subjective irritation, cross-polarized photography, and self-assessment
      questionnaires were completed at baseline, and after 4 and 8 weeks of use. A
      quality of life questionnaire was given at baseline and week 8. RESULTS: Clinical
      evaluations, subject response, and photography confirmed very good tolerability
      of the regimen and effective neutralization of redness by the pigmented products.
      Significant improvements in average erythema scores were observed at 4 and 8
      weeks (P < 0.05), and an improvement in quality of life was confirmed by the
      patient questionnaires. DISCUSSION: The skin care regimen containing Lic A was
      found to be compatible with the sensitive facial skin of patients with rosacea
      and improved the appearance of persistent facial redness. The products were also
      observed to be compatible with daily metronidazole treatment.

PMID- 17177745
TI  - Cosmetic use of polylactic acid for hand rejuvenation: report on 27 patients.
AB  - OBJECTIVE: Polylactic acid (PLA) is effectively used on the face. In the Author's
      opinion it can also be applied successfully to other body areas. The aim of the
      present retrospective study is to estimate the safety and results of this new
      technique in order to improve the hand skeletal status in old patients. MATERIALS
      AND METHODS: Twenty-seven patients were treated in the period from January 2004
      to April 2005 (a total of 109 sessions). Their age averaged 65.9 years. In all
      cases the hand treatment was associated with a face or neck treatment. 150 mg
      polylactic acid was diluted with 0.5 mL of 3% Carbocain and water for injectable
      preparations (from 5 to 8 mL). Intermetacarpal spaces were injected with this
      solution in dosages ranging from 2 to 4 mL with a particular and rigorous
      technique. The protocol, consisting of 3-6 consecutive sessions, is discussed
      below. RESULTS: The results have been evaluated by a Definitive Graduated Score
      (DGS) based on the patient's and doctor's satisfaction scores (from 1 to 10) and
      by the photograph score. They have ranged from 4 to 9 (average of 6.55). No
      important side effects have been detected. There has been one case of fine
      unnoticeable nodulations. In six cases the result has not been satisfactory. In
      seven cases the DGS was higher than 8. CONCLUSION: The fibro-connectival
      restoration of hands is an important step in the global aesthetic treatment of
      old patients. This technique can give good results, particularly if associated
      with peelings and sclerotherapy. Side effects have been acceptable.

PMID- 17177746
TI  - The combination of 2% 4-hydroxyanisole (mequinol) and 0.01% tretinoin effectively
      improves the appearance of solar lentigines in ethnic groups.
AB  - While the efficacy and safety of topical 4-hydroxyanisole (mequinol) 2%/tretinoin
      0.01% therapy has been established in Caucasian populations, those with skin
      types I-II, little research has focused on individuals with darker skin types.
      The purpose of this open-label study was to evaluate the efficacy and safety of
      mequinol 2%/tretinoin 0.01% solution in the treatment of solar lentigines in
      Asian, Latin/Hispanic, and African American ethnic groups with skin types II-V.
      Subjects were required to have >or= 10 solar lentigines on the dorsal
      forearms/hands and >or= 3 on the face. One lesion was designated the target
      lesion, however, all lesions were treated. Patients were treated with topical
      mequinol 2%/tretinoin 0.01% and clinically evaluated at 4, 8, 12, 16, 20, and 24
      weeks as well as 4 weeks following treatment cessation. At each visit, lesions
      were evaluated using Target and Overall Lesion Pigmentation Index scores ranging
      from 0 (lightest) to 8 (darkest), where 4 indicated equal pigment with
      surrounding skin. Efficacy was determined based on pigmentation index scores, and
      safety was assessed using laboratory monitoring and adverse event (AE) reporting.
      Over 80% of the 259 subjects completing this study responded to mequinol
      2%/tretinoin 0.01% therapy, with a majority of subjects maintaining clinical
      benefit at 4 weeks post-treatment. Most AEs reported were tolerable and overall
      mequinol 2%/tretinoin 0.01% therapy had a favorable benefit-to-risk ratio. This
      study therefore supports the theory that topical mequinol 2%/tretinoin 0.01% is
      an effective and safe treatment of solar lentigines in ethnic populations, and in
      those with dark skin types.

PMID- 17177747
TI  - The halo effect: avoiding adverse pigmentation changes following Q-switched ruby
      laser treatment of pigmented birthmarks.

PMID- 17177748
TI  - Superficial chemical peels.
AB  - Superficial chemical peeling (SCP) involves the application of a peeling agent to
      the skin, resulting in destruction of part or all of the epidermis. SCP is mainly
      recommended for facial rejuvenation, photoaging and superficial rhytides,
      pigmentary dyschromias and acne. It can be used on all Fitzpatrick skin types, no
      sedation is needed, and the desquamation is usually well accepted. Overpeel and
      complications are very rare. The most commonly used SCP agents are glycolic acid
      20-70%, trichloroacetic acid 10-35%, Jessner's solution, salicylic acid, pyruvic
      acid, resorcinol 30-50% preparations, and solid carbon dioxide. The careful
      selection of patients is critical for the outcome of a SCP and contraindications
      must be seriously considered. The peel procedure is generally common for all SCP
      agents but a good knowledge of the specific characters of each agent is of great
      importance in order to decide which to use for each individual patient.

PMID- 17177749
TI  - Use of intense pulsed light and a retinyl-based cream as a potential treatment
      for cellulite: a pilot study.
AB  - BACKGROUND: There are few therapeutic treatments established for cellulite.
      OBJECTIVE: We studied the response of intense pulsed light (IPL) treatment with
      or without a compounded prescription retinyl-based cream on a small group of
      patients who had visible cellulite present on the buttocks and thigh regions.
      PATIENTS AND METHODS: Twenty patients were selected to complete a 12-week course
      of IPL treatment either with or without a retinyl-based cream. Assessment was
      based on visual evaluation, photographs, skin ultrasounds, and patient
      satisfaction. RESULTS: Fifteen (75%) completed the study, and nine (60%) had a
      self-improvement rating of >or= 50%. Seven (78%) of nine patients used IPL/cream.
      Of the remaining six (40%) completing the study, four (27%) had self-improvement
      ratings of 25-50% and two (13%; IPL only) were considered treatment failures with
      a rating of 10-25%. Both IPL/cream and IPL-only groups exhibited an improvement
      in the smoothness of the affected area even following weight gain. Skin
      ultrasounds confirmed an increase in the deposition of collagen. During an 8
      month phone follow-up, 8 (67%) of 12 responding reported the same or improved
      results. CONCLUSION: IPL treatment with or without a retinyl-based cream can
      improve the appearance of peau d'orange cellulite, though the cream may augment
      cosmetic improvement. This approach is well tolerated, has minimal side effects,
      and is accompanied by a high degree of patient satisfaction.

PMID- 17177752
TI  - Pulsed radiofrequency in chronic pain management: looking for the best use of
      electrical current.

PMID- 17177750
TI  - Novel cutaneous uses for botulinum toxin type A.
AB  - Botulinum toxin type A is a neurotoxin produced by the bacterium Clostridium
      botulinum which causes a flaccid muscle paralysis. It has been used extensively
      in the field of dermatology for the treatment of dynamic rhytides and in the
      treatment of hyperhidrosis. Botulinum toxin has an excellent safety profile and
      few side effects when used for these purposes. Recently, botulinum toxin has also
      been used experimentally in a number of other dermatologic conditions with good
      results. These conditions include: persistent facial flushing, gustatory sweating
      and epiphora, anal fissures, familial benign pemphigus (Hailey-Hailey disease),
      dyshidrotic eczema, and following surgical wound closures. While randomized,
      controlled prospective trials are still needed to further understand the efficacy
      and safety of botulinum toxin in these conditions, anecdotal and case report data
      suggest that botulinum toxin is both safe and efficacious in these and many other
      procedures.

PMID- 17177753
TI  - Pain: disease or dis-ease? The John Bonica Lecture: presented at the third World
      Congress of World Institute of Pain, Barcelona 2004.
AB  - Chronic pain has only recently been recognized as an important health care issue.
      There is no widely shared agreement as to the best ways to diagnose and treat
      chronic pain patients. Pain management is a chaotic component of contemporary
      medicine. I argue that we need to think of chronic pain as a disease in its own
      right and develop our specialty of pain management on the basis of evidence for
      treatment outcomes. The current chaotic state confuses patients, health care
      providers, and payers. It is possible that pain management may disappear from
      health care if we do not improve our understanding of chronic pain and how to
      best treat those who suffer.

PMID- 17177754
TI  - Evolution of the neuromatrix theory of pain. The Prithvi Raj Lecture: presented
      at the third World Congress of World Institute of Pain, Barcelona 2004.
AB  - The neuromatrix theory of pain proposes that pain is a multidimensional
      experience produced by characteristic "neurosignature" patterns of nerve impulses
      generated by a widely distributed neural network-the "body-self neuromatrix"-in
      the brain. These neurosignature patterns may be triggered by sensory inputs, but
      they may also be generated independently of them. Acute pains evoked by brief
      noxious inputs have been meticulously investigated by neuroscientists, and their
      sensory transmission mechanisms are generally well understood. In contrast,
      chronic pain syndromes, which are often characterized by severe pain associated
      with little or no discernable injury or pathology, remain a mystery. Furthermore,
      chronic psychological or physical stress is often associated with chronic pain,
      but the relationship is poorly understood. The neuromatrix theory of pain
      provides a new conceptual framework to examine these problems. It proposes that
      the output patterns of the body-self neuromatrix activate perceptual,
      homeostatic, and behavioral programs after injury, pathology, or chronic stress.
      Pain, then, is produced by the output of a widely distributed neural network in
      the brain rather than directly by sensory input evoked by injury, inflammation,
      or other pathology. The neuromatrix, which is genetically determined and modified
      by sensory experience, is the primary mechanism that generates the neural pattern
      that produces pain. Its output pattern is determined by multiple influences, of
      which the somatic sensory input is only a part, that converge on the neuromatrix.

PMID- 17177755
TI  - Pregabalin for pain management.
AB  - Pregabalin is a new analog of the neurotransmitter gamma-aminobutyric acid
      (GABA). It is an alpha2-delta (alpha2-delta) ligand that has analgesic,
      anticonvulsant, and anxiolytic activity. Alpha2-delta is an auxiliary protein
      associated with voltage-gated calcium channels. Pregabalin binds potently to the
      alpha2-delta subunit resulting in modulation of calcium channels and reduction in
      the release of several neurotransmitters, including glutamate, norepinephrine,
      serotonin, dopamine, and substance P. This review discusses the pharmacology of
      this medication as well as available studies in patients.

PMID- 17177756
TI  - Thermocoagulation of the ganglion impar or ganglion of Walther: description of a
      modified approach. Preliminary results in chronic, nononcological pain.
AB  - The ganglion impar, a single structure usually found at the anterior aspect of
      the sacrococcygeal joint, is the lowest ganglion of the paravertebral sympathetic
      chain. Its blockade is indicated in visceral pain syndromes and/or sympathetic
      pain syndromes of the perineal region. Several approaches to this block have been
      described, mainly through the anococcygeal or sacrococcygeal ligaments. We
      propose a modified approach to thermocoagulation of the ganglion impar, using a
      two-needle technique, the first one, placed through the sacrococcygeal ligament,
      the transsacrococcygeal needle, and the second one through a coccygeal disc, the
      transdiscal needle. The thermocoagulation technique that we employ uses a
      conventional radiofrequency application of 80 degrees C for 80 seconds through
      each needle. In this prospective study, 13 patients with chronic perineal,
      noncancer-related pain were followed for a maximum of 6 months. All of these
      patients underwent diagnostic ganglion impar block with local anesthetic prior to
      inducing neurodestruction with conventional radiofrequency application, as a
      positive result to the diagnostic local anesthetic block was a requisite for
      radiofrequency neurodestruction. We measured pain using a visual analog scale
      (VAS) before and after treatment. Statistical significance was assessed using the
      Mann-Whitney U-test and Wilcoxon range summation test. Initially the VAS was
      equal to or greater than 7. After therapy the VAS decreased by an average of 50%
      in the whole group. There were no adverse events. Our result show that this
      proposed modified approach to the block and use of radiofrequency for the
      ganglion impar is useful for the treatment of perineal noncancer-related pain.

PMID- 17177757
TI  - Pulsed radiofrequency for radicular pain due to a herniated intervertebral disc-
      an initial report.
AB  - Pulsed radiofrequency (PRF) has been used for the treatment of radicular pain,
      due to a herniated intervertebral disc, but so far the data are anecdotal. This
      is a retrospective study on 13 consecutive patients with this type of pain, at
      levels L3 to S1. All patients had a diagnosis confirmed by imaging, all had
      neurological abnormalities, and all were scheduled for surgical intervention. All
      12 patients who had a profession had stopped working. Treatment consisted of
      application of PRF to the dorsal root ganglion of the affected segmental nerve,
      or in the case of S1 to the segmental nerve at the level of the S1 foramen. One
      patient underwent disc surgery, and one other patient underwent a spinal fusion 1
      year following PRF treatment. He had no leg pain at the time of operation. The
      remaining patients did not require surgical intervention. The numeric rating
      scale (NRS) score fell from 7.83 to 2.25 over the first 2 weeks, followed by a
      gradual further fall to 0.27 at the final follow-up, 15.8 (11 to 23) months after
      the procedure. Compared with the initial NRS score the data were significant (P <
      0.01) from 4 weeks after the procedure. Neurological abnormalities resolved
      except in one patient, who had decreased sensibility in a small area in the L3
      dermatome at the last follow-up. All professionally active patients went back to
      work after 0.49 months (0.1 to 1). It is concluded that PRF may potentially be a
      viable alternative for epidural steroid injections in the treatment of acute
      radicular pain, due to a herniated intervertebral disc, and that further studies,
      including a control group, should be carried out to establish the value of this
      method.

PMID- 17177758
TI  - Percutaneous lumbar discectomy: one-year follow-up in an initial cohort of fifty
      consecutive patients with chronic radicular pain.

PMID- 17177759
TI  - Prediction of the distance from the skin to the lumbar epidural space in the
      Greek population, using mathematical models.
AB  - BACKGROUND AND OBJECTIVES: The skin to lumbar epidural space distance (SLED) is
      variable, and therefore the ability to clinically predict the SLED may help
      increase the success of epidural anesthesia/analgesia. The goal of this study was
      to determine the relationship between the SLED and demographic/anthropometric
      variables in the Greek population, and develop a mathematical model for its
      prediction. METHODS: This prospective randomized study enrolled 406 male and
      female Greek patients who required an epidural block as part of their anesthetic
      management. With patients placed in the left lateral and knee-chest position, the
      lumbar epidural space was located by the loss of resistance to normal saline
      technique. Statistical analysis was used to identify the relationship between
      SLED, and the following variables were evaluated: age, weight, height, body mass
      index, body surface area, intervertebral space used, pregnancy, and geographic
      origin within Greece. RESULTS: No adverse events or dural punctures occurred.
      Mean SLED in the general population was 4.98 +/- 0.95 cm, with values
      significantly higher in males (5.37 +/- 0.88 cm) compared with females (4.83 +/-
      0.93 cm). SLED was best associated with weight, body surface area, and body mass
      index. Mathematical formulae for prediction of SLED in the general population and
      the female population were derived from linear regression analysis. These
      formulae were able to predict approximately half of the observed variability in
      SLED. CONCLUSIONS: While mathematical models of SLED can be a useful tool, they
      should not be exclusively relied on in the clinical setting, but rather should be
      used as an adjunct to standardized techniques to improve the safety and efficacy
      of epidural anesthesia/analgesia.

PMID- 17177760
TI  - Editorial expression of concern regarding: Kaye AD, Banister RE, Hoover JM, et
      al. Chronic pain and ultrarapid opioid detoxification. Pain Practice 2005;5(1):33
      42.

PMID- 17177761
TI  - Evidence-based medicine and clinical trials in pain practice and orthopedics.
AB  - Medical practices should be based on scientific findings pursuant to the rules of
      evidence-based medicine. Quality standards for interventional pain therapy and
      orthopedic clinical studies have been lacking. As a result, the efficacy of many
      forms of therapy is insufficiently documented, making the level of evidence low.
      This article identifies common deficiencies in the conduct of clinical trials, as
      well as limitations in conducting randomized controlled studies. Recommendations
      for improvement are provided. The discussion provides the clinically active
      physician with interpretation aids for the evaluation of meta-analyses, supports
      personal evidence-based decisions, and reviews the most important principles for
      planning and conducting of experimental clinical studies. Current examples in the
      literature verify the implementation of these principles and present current
      findings in accordance with evidence-based medicine (EBM) criteria. In spite of
      an increasing emergence of EBM-based studies, we conclude that the number of well
      designed, high quality, controlled studies conducted in accordance with the
      guidelines of Good Clinical Practice examining interventional pain therapy and
      orthopedic clinical studies remains unacceptably low.

PMID- 17177762
TI  - Ethical and epistemological problems when applying evidence-based medicine to
      pain management.
AB  - Epistemology, or the theory of knowledge, is a branch in philosophy concerned
      with the definitions of knowledge and evidence. Although evidence-based medicine
      (EBM) has a strong ethical imperative behind it, rooted in the concern to do no
      harm, to do one's best for one's patients, and by doing so--eliminating waste, it
      still harbors within it serious epistemological limits. These include
      methodological and ethical limits to perform randomized controlled trials, the
      idea of "hierarchy of evidence" which may provide conclusions well short of
      medical knowledge, and the unique use of a single particular theory of
      statistical inference which is far from consensual. In this article, we review
      these difficulties and suggest that EBM is at best a methodological solution to
      some clinical phenomena, but remains blind to mechanisms of explanation and
      causation needed, in order to advance our knowledge. Further research in the
      theory of evidence and inference, causation and correlation, clinical judgment
      and collective knowledge, the structure of medical theory, and the nature of
      clinical effectiveness are needed.

PMID- 17177763
TI  - Evidence-based clinical practice guidelines for interdisciplinary rehabilitation
      of chronic nonmalignant pain syndrome patients.
AB  - This is an update to evidence-based practice guidelines for chronic nonmalignant
      pain syndrome patients first published in 1995 and revised in 1999. The current
      guidelines recommend interdisciplinary-focused rehabilitation, which is goal
      directed and time-limited. Emphasis is placed on educating patients in active
      self-management techniques that stress maximizing function. Integrated treatment
      involving medical, psychological/behavioral, physical/occupational therapy, and
      disability/vocational interventions are recommended on an outpatient basis
      whenever clinically possible. Patient selection criteria are delineated. Updated
      references providing evidence-based support for the recommendations are provided,
      including the use of opioids and sedative-hypnotic medications, injection and
      block procedures, acupuncture, implantable spinal infusion and stimulation
      devices, and other invasive spinal surgery procedures such as intradiscal
      electrothermal therapy. Guideline integration and early detection and
      intervention with chronic pain syndrome patients are encouraged.

PMID- 17177764
TI  - Percutaneous vertebroplasty in octogenarians: results and follow-up.
AB  - OBJECTIVES: To determine pain relief, performance status, morbidity, and
      mortality associated with percutaneous vertebroplasty for spinal pain in patients
      aged 80 years and older. DESIGN: Prospective, descriptive, third-party
      independent interview, clinical audit. SETTING: University Hospital, Geneva,
      Switzerland. PARTICIPANTS: Patients aged 80 years and older who underwent
      vertebroplasty between August 1997 and August 2004 because of vertebral fractures
      from osteoporotic or malignant etiologies. METHODS: Primary outcome measures were
      verbal rating scale (VRS) (0--no pain, 5--intolerable) and Eastern Cooperative
      Oncology Group (ECOG) performance status scale (0--normal activity, 4--unable to
      get out of bed) before and after procedure. Patients were interviewed 8 to 35
      months post treatment (mean 25), independently assessed for pain relief,
      analgesic consumption, and overall satisfaction by using the American Society of
      Anesthesiologists (ASA) Outcome Measures questionnaire. RESULTS: Mean VRS scores
      significantly decreased from 4.86 +/- 0.64 to 2.39 +/- 1.14 (P < 0.05), and mean
      ECOG performance scores improved from 1.87 +/- 0.97 to 1.29 +/- 1.06 (P < 0.05)
      after treatment. When patients were analyzed by etiology (group 1--cancer; group
      2--osteoporosis), both groups significantly reduced their VRS (P < 0.05);
      however, only group I significantly improved their performance (P < 0.05; P =
      0.334, respectively). Nine patients answered the ASA questionnaire (18 deceased,
      1 demented, 1 lost to follow-up) and reported an improvement in their ability to
      perform daily tasks. No early or late complications were observed; none of the
      deaths were procedure-related. CONCLUSIONS: Percutaneous vertebroplasty is a
      safe, minimally invasive, well-tolerated analgesic procedure among octogenarians
      suffering from spinal pain, permitting increased activities of daily living. Pain
      reduction is significant regardless of the etiology; performance scores are
      significantly improved in cancer pain.

PMID- 17177765
TI  - New approach for spinal cord stimulation trial.
AB  - Spinal cord stimulation trial phase has remained unchanged for years. The common
      practice to connect a lead to an external transmitter is not optimal. The
      operational mode of transmitter is different from implanted system and external
      bulky device interferes with patient's daily routine. Optimization in the trial
      period may increase patient's satisfaction and improve outcome of upcoming
      permanent implantation. The proposed new trial design can be a simple and logical
      solution of the problem.

PMID- 17177766
TI  - Postherpetic neuralgia: the never-ending challenge.
AB  - Postherpetic neuralgia (PHN) is defined as pain that persists 1 to 3 months
      following the rash of herpes zoster (HZ). PHN affects about 50% of patients over
      60 years of age and 15% of all HZ patients. Patients with PHN may experience two
      types of pain: a steady, aching, boring pain and a paroxysmal lancinating pain,
      usually exacerbated by contact with the involved skin. Herpes zoster is initially
      a clinical diagnosis, based on the observation of a typical dermatomal
      distribution of rash and radicular pain. HZ is pathologically characterized by
      inflammatory necrosis of dorsal root ganglia, occasionally associated with
      evidence of neuritis, leptomeningitis, and segmental unilateral degeneration of
      related motor and sensory roots. Although acyclovir has been used successfully as
      standard therapy for varicella zoster virus (VZV) infection in the past decade,
      resistant strains of VZV are often recognized in immunocompromised patients.
      Therapy with acyclovir and the use of corticosteroids have been reported to
      prevent PHN in up to 60% of HZ patients. Management of chronic pain in PHN is
      more problematic. The only therapy proven effective for PHN in controlled study
      is the use of tricyclic antidepressants, including amitriptyline and desipramine.
      There is good evidence of efficacy from randomized trials that gabapentin and
      pregabalin (new anticonvulsant drugs) are of benefit in the reduction of pain
      from PHN. As alternative therapies, topical agents such as capsaicin, lidocaine
      or opioid analgesic treatment may give satisfactory results. Interventions with
      low risk, such as transcutaneous electrical nerve stimulation (TENS), are
      appropriate. Evidence is scant for the value of surgical and procedural
      interventions in general, although there are numerous, small studies supporting
      the use of specific interventions such as nerve blocks, neurosurgical procedures,
      and neuroaugmentation. Although antiviral agents are appropriate for acute HZ,
      and the use of neural blockade and sympathetic blockade may be helpful in
      reducing pain in selected patients with HZ, there is little evidence that these
      interventions will reduce the likelihood of developing PHN. Postherpetic
      neuralgia remains a difficult pain problem. This review describes the
      epidemiology and pathophysiology of PHN and discusses proposed mechanisms of pain
      generation with emphasis on the various pharmacological treatments and invasive
      modalities currently available.

PMID- 17177767
TI  - Pain research update from a genetic point of view.
AB  - Molecular biology investigates the genetic causes of many diseases. Currently,
      molecular biology in pain research lags behind the investigations of the
      molecular basis of mental disorders. A significant challenge in pain genetic
      research is the fact that pain involves emotional factors. Tools available for
      pain measurements and interindividual comparisons have been imperfect. Another
      problem relates to research ethics. Unlike animal studies, there is very limited
      ability to evoke experimental pain in a group of humans with precisely defined
      age, sex, medication, and pain experience. Nevertheless, pain investigations at
      the gene level have commenced. Recent progress in molecular biology has enabled
      gene expression modulation in animal models using "knockout," "oligo-antisense,"
      and viral vector techniques. These methods enable investigation, at molecular
      level, as to which of the approximately 30,000 genes of the human genome might be
      involved in pain mediation, which of these are polymorphic, and which
      polymorphisms are responsible for interindividual differences in pain perception.
      Recently, the genetic bases of familial hemiplegic migraine and congenital
      insensitivity to pain with anhidrosis have been shown. In the last 6 years,
      genetic pain research has focused on potential gene therapy for patients with
      chronic pain. Results of these studies are encouraging and potentially applicable
      to clinical practice in the near future.

PMID- 17177769
TI  - Low back pain.

PMID- 17177768
TI  - Extended-release epidural morphine (DepoDur): an old drug with a new profile.
AB  - The FDA has recently approved a novel formulation for epidural morphine
      administration that allows a single injection to provide 48 hours of analgesia.
      This may eliminate the need for an indwelling epidural catheter in some
      circumstances and therefore be particularly well suited to postoperative
      situations where anticoagulation is required. Other uses that have been less
      thoroughly studied should be approached with due caution.

PMID- 17177770
TI  - Phantom limb pain treatment with mirtazapine: a case series.
AB  - OBJECTIVES: To pilot the efficacy of mirtazapine for relief of phantom limb pain
      (PLP); to correlate the putative drug mechanism with theoretical PLP mechanisms;
      and to develop a rationale for further study of mirtazapine in this population.
      DESIGN: Open-label case series. SUBJECTS/PATIENTS: Four individuals with PLP for
      at least 3 months after amputation. METHODS: All subjects received oral
      mirtazapine between 7.5 and 30 mg/day. An 11-point numeric rating scale (0 to 10)
      measured pain intensity and relief during monitored outpatient follow-up visits.
      RESULTS/DISCUSSION: Mirtazapine use improved the PLP experienced by these
      subjects by at least 50%. Subjects with PLP-related sleeping difficulties
      reported the greatest pain relief concomitant with improved sleep quality. One
      subject was able to eliminate the use of a selective serotonin reuptake inhibitor
      antidepressant while using mirtazapine for PLP and depression without change in
      mood or affect. Mirtazapine enhances noradrenergic and serotonergic activity and
      may modulate PLP by central mechanisms. Current concepts of the proposed
      pathophysiology of PLP and the hypothetical impact of mirtazapine are discussed.
      CONCLUSION: Mirtazapine may be an effective treatment for PLP that can also
      potentially enhance sleep and mood. This information provides preliminary
      reinforcement for more formal, controlled studies concerning mirtazapine use in
      PLP.

PMID- 17177771
TI  - Myofascial pain syndrome affecting the piriformis and the obturator internus
      muscle.
AB  - The obturator internus muscle is an external rotator of the hip. Obturator
      internus injury may occur and be hidden by the piriformis syndrome. Clinical
      symptoms may offer some clues to the clinician. The selective injection technique
      described here facilitates precise diagnosis.

PMID- 17177772
TI  - Superior cluneal nerve entrapment eight years after decubitus surgery.
AB  - BACKGROUND AND OBJECTIVE: Superior cluneal nerve (SCN) entrapment is one of the
      infrequent etiologies of low back pain (LBP), which is rarely diagnosed. Few
      clinical reports have been published in the literature. We present a case of
      severe LBP radiating to the ipsilateral buttock after decubitus surgery. CASE
      REPORT: A 62-year-old man weighing 85 kg presented to the algology department,
      suffering from severe LBP of 6 months duration. The pain was in the right iliac
      crest region with radiation to the ipsilateral buttock. After admission, his
      history was taken, physical examination was performed, and further evaluations
      were made. He was suspected of having facet and right sacroiliac joint pain. Two
      tender points were found 6.5 and 7.5 cm to the right of the midline over the
      iliac crest. Local anesthetic with corticosteroid was injected at the tender
      points over the right iliac crest. Five minutes after the injection, the pain
      dissipated. CONCLUSION: SCN entrapment should be considered in patients who
      suffer from LBP radiating to the iliac crest and buttock after other causes of
      LBP have been excluded.

PMID- 17177775
TI  - Letter to the editor regarding Fukshansky M et al., The role of opioids in cancer
      pain management. Pain Practice 2005;5(1);43-54.

PMID- 17177776
TI  - Disc or disk?

PMID- 17177774
TI  - Letter to the editor regarding Reig et al., Thermocoagulation of the ganglion
      impar of Walther: description of a modified approach. Preliminary results in
      chronic, nononcological pain. Pain Practice 2005;5(2):103-110.

PMID- 17177780
TI  - Opinion piece: genomics and crop plant science in Europe.
AB  - Recent report reviews and funding initiatives in the field of plant genomic
      research are considered in the context of their translation into practical and
      economic value via plant breeding. It is concluded that there is a deficit in
      investment and that a change in working styles towards knowledge sharing and
      connectivity is required.

PMID- 17177781
TI  - Mitigation of establishment of Brassica napus transgenes in volunteers using a
      tandem construct containing a selectively unfit gene.
AB  - Transgenic oilseed rape (Brassica napus) plants may remain as 'volunteer' weeds
      in following crops, complicating cultivation and contaminating crop yield.
      Volunteers can become feral as well as act as a genetic bridge for the transfer
      of transgenes to weedy relatives. Transgenic mitigation using genes that are
      positive or neutral to the crop, but deleterious to weeds, should prevent
      volunteer establishment, as previously intimated using a tobacco (Nicotiana
      tabacum) model. A transgenically mitigated (TM), dwarf, herbicide-resistant
      construct using a gibberellic acid-insensitive (Deltagai) gene in the B. napus
      crop was effective in offsetting the risks of transgene establishment in
      volunteer populations of B. napus. This may be useful in the absence of
      herbicide, e.g. when wheat is rotated with oilseed rape. The TM dwarf B. napus
      plants grown alone had a much higher yield than the non-transgenics, but were
      exceedingly unfit in competition with non-transgenic tall cohorts. The
      reproductive fitness of TM B. napus was 0% at 2.5-cm and 4% at 5-cm spacing
      between glasshouse-grown plants relative to non-transgenic B. napus. Under screen
      house conditions, the reproductive fitness of TM B. napus relative to non
      transgenic B. napus was less than 12%, and the harvest index of the TM plants was
      less than 40% of that of the non-transgenic competitors. The data clearly
      indicate that the Deltagai gene greatly enhances the yield in a weed-free
      transgenic crop, but the dwarf plants can be eliminated when competing with non
      transgenic cohorts (and presumably other species) when the selective herbicide is
      not used.

PMID- 17177782
TI  - Mitigation using a tandem construct containing a selectively unfit gene precludes
      establishment of Brassica napus transgenes in hybrids and backcrosses with weedy
      Brassica rapa.
AB  - Transgenic oilseed rape (Brassica napus) plants can interbreed with nearby weedy
      Brassica rapa, potentially enhancing the weediness and/or invasiveness of
      subsequent hybrid offspring. We have previously demonstrated that transgenic
      mitigation effectively reduces the fitness of the transgenic dwarf and herbicide
      resistant B. napus volunteers. We now report the efficacy of such a tandem
      construct, including a primary herbicide-resistant gene and a dwarfing mitigator
      gene, to preclude the risks of gene establishment in the related weed B. rapa and
      its backcross progeny. The transgenically mitigated and non-transgenic B. rapa x
      B. napus interspecific hybrids and the backcrosses (BC(1)) with B. rapa were
      grown alone and in competition with B. rapa weed. The reproductive fitness of
      hybrid offspring progressively decreased with increased B. rapa genes in the
      offspring, illustrating the efficacy of the concept. The fitness of F(2)
      interspecific non-transgenic hybrids was between 50% and 80% of the competing
      weedy B. rapa, whereas the fitness of the comparable T(2) interspecific
      transgenic hybrids was never more than 2%. The reproductive fitness of the
      transgenic T(2) BC(1) mixed with B. rapa was further severely suppressed to 0.9%
      of that of the competing weed due to dwarfism. Clearly, the mitigation technology
      works efficiently in a rapeseed crop-weed system under biocontainment-controlled
      environments, but field studies should further validate its utility for
      minimizing the risks of gene flow.

PMID- 17177783
TI  - The Lem2 gene promoter of barley directs cell- and development-specific
      expression of gfp in transgenic plants.
AB  - Transgenic approaches to combating fungal pathogens, such as Fusarium
      graminearum, require the targeting of antifungal gene expression in tissues of
      developing seed spikes of cereal grains, especially lemmas and epicarps. The Lem2
      gene of barley encodes a lectin-like protein that is strongly up-regulated by
      salicylic acid and is preferentially expressed in lemmas, paleas (lemma/palea)
      and coleoptiles. Transient expression studies have indicated that the proximal 
      75/+70 region (relative to the transcription start site) determines organ
      specificity. In the present study, Golden Promise barley stably transformed with
      Morex Lem2 promoter/gfp reporter constructs displayed cell- and development
      specific expression of gfp (green fluorescent protein gene). This expression
      corresponded to the expression seen in Northern blots of Morex organs. Under the
      full-length promoter, strong GFP fluorescence was observed in the lemma/palea,
      glumes, coleoptile, auricle and ligule. Weak GFP fluorescence was also observed
      in the rachis, tips of primary leaves and the leaf sheath. Unexpectedly, strong
      expression occurred in the epicarp, even though Lem2 is not expressed in this
      organ in Morex. Studies showed that the Lem2 promoter is more highly methylated
      in the epicarp than in the lemma of Morex. In the lemma/palea, gfp underwent a
      temporal shift in expression from the mesophyll to specialized epidermal cork
      cells. Similar to the lemma/palea, expression in the leaf sheath was localized in
      the cork cells. Progressive 5' deletions of the promoter to nucleotide -75
      gradually reduced the level of gfp expression, but tissue- and cell-specific
      expression was retained.

PMID- 17177784
TI  - Pod shatter-resistant Brassica fruit produced by ectopic expression of the
      FRUITFULL gene.
AB  - Arabidopsis has proven to be extremely useful as a reference organism for studies
      in plant biology, and huge efforts have been employed to unravel various
      mechanisms of Arabidopsis growth. A major challenge now is to demonstrate that
      this wealth of knowledge can be used for global agricultural and environmental
      improvement. Brassica species are closely related to Arabidopsis and represent
      ideal candidates for model-to-crop approaches as they include important crop
      plants, such as canola. Brassica plants normally disperse their seeds by a pod
      shattering mechanism. Although this mechanism is an advantage in nature,
      unsynchronized pod shatter constitutes one of the biggest problems for canola
      farmers. Here, we show that ectopic expression of the Arabidopsis FRUITFULL gene
      in Brassica juncea is sufficient to produce pod shatter-resistant Brassica fruit
      and that the genetic pathway leading to valve margin specification is conserved
      between Arabidopsis and Brassica. These studies demonstrate a genetic strategy
      for the control of seed dispersal that should be generally applicable to diverse
      Brassica crop species to reduce seed loss.

PMID- 17177785
TI  - Manganese peroxidase from the white-rot fungus Phanerochaete chrysosporium is
      enzymatically active and accumulates to high levels in transgenic maize seed.
AB  - Manganese peroxidase (MnP) has been implicated in lignin degradation and thus has
      potential applications in pulp and paper bleaching, enzymatic remediation and the
      textile industry. Transgenic plants are an emerging protein expression platform
      that offer many advantages over traditional systems, in particular their
      potential for large-scale industrial enzyme production. Several plant expression
      vectors were created to evaluate the accumulation of MnP from the wood-rot fungus
      Phanerochaete chrysosporium in maize seed. We showed that cell wall targeting
      yielded full-length MnP, whereas cytoplasmic localization resulted in multiple
      truncated peroxidase polypeptides as detected by immunoblot analysis. In
      addition, the use of a seed-preferred promoter dramatically increased the
      expression levels and reduced the negative effects on plant health. Multiple
      independent transgenic lines were backcrossed with elite inbred corn lines for
      several generations with the maintenance of high-level expression, indicating
      genetic stability of the transgene.

PMID- 17177786
TI  - Increased field resistance to Tilletia caries provided by a specific antifungal
      virus gene in genetically engineered wheat.
AB  - The field performance of a viral gene in two Swiss wheat (Triticum aestivum)
      varieties showed 10% increased fungal resistance against Tilletia caries
      (stinking smut). To the best of our knowledge, this is the first report of
      improved resistance against any fungus in the field achieved by genetic
      engineering in wheat. The genetically modified wheat lines previously showed a c.
      30% decrease in symptoms of T. caries in the glasshouse (Clausen, M., Krauter,
      R., Schachermayr, G., Potrykus, I. and Sautter, C. (2000) Antifungal activity of
      a virally encoded gene in transgenic wheat. Nat. Biotechnol. 18, 446-449),
      depending on the fungal strain inoculated. A glasshouse experiment run in
      parallel to the field test, and using the same collection of T. caries, gave the
      same results. In a dose-response experiment with isolated fungal strains, in
      which the infection pressure was varied via the spore concentration, the
      transgene behaved as a quantitative resistance gene and shifted the S-shaped dose
      response curve towards higher resistance. The transgene was shown to be highly
      specific for fungi of the order Ustilaginales. Tests of the transgene using cell
      cultures of eukaryotes, including hamster and human, showed no significant side
      effects with respect to biosafety. Endogenous pathogen-related genes were also
      activated on fungal infection in the presence of the kp4 transgene.

PMID- 17177787
TI  - Transgenic expression and recovery of biologically active recombinant human
      insulin from Arabidopsis thaliana seeds.
AB  - The increased incidence of diabetes, coupled with the introduction of alternative
      delivery methods that rely on higher doses, is expected to result in a
      substantial escalation in the demand for affordable insulin in the future.
      Limitations in the capacity and economics of production will make it difficult
      for current manufacturing technologies to meet this demand. We have developed a
      novel expression and recovery technology for the economical manufacture of
      biopharmaceuticals from oilseeds. Using this technology, recombinant human
      precursor insulin was expressed in transgenic plants. Plant-derived insulin
      accumulates to significant levels in transgenic seed (0.13% total seed protein)
      and can be enzymatically treated in vitro to generate a product with a mass
      identical to that of the predicted product, DesB(30)-insulin. The biological
      activity of this product in vivo and in vitro was demonstrated using an insulin
      tolerance test in mice and phosphorylation assay performed in a mammalian cell
      culture system, respectively.

PMID- 17177788
TI  - Up-regulation of sucrose synthase and UDP-glucose pyrophosphorylase impacts plant
      growth and metabolism.
AB  - The effects of the overexpression of sucrose synthase (SuSy) and UDP-glucose
      pyrophosphorylase (UGPase) on plant growth and metabolism were evaluated in
      tobacco (Nicotiana tabacum cv. Xanthi). T(1) transgenic plants expressing either
      gene under the control of a tandem repeat cauliflower mosaic virus 35S promoter
      (2x35S) or a xylem-localized 4CL promoter (4-coumarate:CoA ligase; 4CL) were
      generated, and reciprocally crossed to generate plants expressing both genes.
      Transcript levels, enzyme activity, growth parameters, fibre properties and
      carbohydrate content of stem tissue were quantified. The expression profiles of
      both genes confirmed the expression pattern of the promoters: 2x35S expressed
      more strongly in leaves, while 4CL expression was highest in stem tissue. In
      depth plant characterization revealed that the single-transgene lines showed
      significant increases in the height growth compared with corresponding control
      lines. The double-transgene plants demonstrated an additive effect, proving to be
      even taller than the single-transgene parents. Several of these lines had
      associated increases in soluble sugar content. Although partitioning of storage
      carbohydrates into starch or cellulose was not observed, the increased height
      growth and increases in soluble carbohydrates suggest a role for SuSy as a marker
      in sink strength and lend credit to the function of UGPase in a similar role. The
      up-regulation of these two genes, although not increasing the percentage
      cellulose content, was effective in increasing the total biomass, and thus the
      overall cellulose yield, from a given plant.

PMID- 17177789
TI  - Regulation of Arabidopsis thaliana 4-coumarate:coenzyme-A ligase-1 expression by
      artificial zinc finger chimeras.
AB  - The use of artificial zinc finger chimeras to manipulate the expression of a gene
      of interest is a promising approach because zinc finger proteins can be
      engineered to bind any given DNA sequence in the genome. We have previously shown
      that a zinc finger chimera with a VP16 activation domain can activate a reporter
      gene in transgenic Arabidopsis thaliana (Sanchez, J.P., Ullman, C., Moore, M.,
      Choo, Y. and Chua, N.H. (2002) Regulation of gene expression in Arabidopsis
      thaliana by artificial zinc finger chimeras. Plant Cell Physiol. 43, 1465-1472).
      Here, we report the use of artificial zinc finger chimeras to specifically
      regulate the 4-coumarate:coenzyme-A ligase-1 (At4CL1) gene in A. thaliana. At4CL1
      is a key enzyme in lignin biosynthesis and the down-regulation of At4CL1 can lead
      to a decrease in lignin content, which has a significant commercial value for the
      paper industry. To this end, we designed zinc finger chimeras containing either
      an activation or a repression domain, which bind specifically to the At4CL1
      promoter region. Transgenic lines expressing a zinc finger chimera with the VP16
      activation domain showed an increase in At4CL1 expression and enzyme activity. In
      contrast, transgenic lines expressing a chimera with the KOX (KRAB) repression
      domain displayed repression of At4CL1 expression and enzyme activity. The
      activation of At4CL1 expression produced an increase in lignin content, and
      transgenic plant stems showed ectopic lignin distribution. Repression of the
      At4CL1 gene resulted in reduced lignin content, and lignin distribution in
      transgenic stems was severely diminished. Our results confirm and extend previous
      studies of gene regulation using various artificial zinc finger chimeras in
      animal and plant systems, and show that this system can be used to up- and down
      regulate the expression of an endogenous plant gene such as At4CL1.

PMID- 17177790
TI  - Gelatinization temperature of rice explained by polymorphisms in starch synthase.
AB  - The cooking quality of rice is associated with the starch gelatinization
      temperature (GT). Rice genotypes with low GT have probably been selected for
      their cooking quality by humans during domestication. We now report polymorphisms
      in starch synthase IIa (SSIIa) that explain the variation in rice starch GT.
      Sequence analysis of the eight exons of SSIIa identified significant polymorphism
      in only exon 8. These single nucleotide polymorphisms (SNPs) were determined in
      70 diverse genotypes of rice. Two SNPs could classify all 70 genotypes into
      either high GT or low GT types which differed in GT by 8 degrees C. 'A' rather
      than 'G' at base 2412 determined whether a methionine or valine was present at
      the corresponding amino acid residue in SSIIa, whilst two adjacent SNPs at bases
      2543 and 2544 coded for either leucine (GC) or phenylalanine (TT). Rice varieties
      with high GT starch had a combination of valine and leucine at these residues. In
      contrast, rice varieties with low GT starch had a combination of either
      methionine and leucine or valine and phenylalanine at these same residues. At
      least two distinct polymorphisms have apparently been selected for their
      desirable cooking qualities in the domestication of rice.

PMID- 17177791
TI  - Manipulation of starch granule size distribution in potato tubers by modulation
      of plastid division.
AB  - Starch granule size is an important parameter for starch applications in
      industry. Starch granules are formed in amyloplasts, which are, like
      chloroplasts, derived from proplastids. Division processes and associated
      machinery are likely to be similar for all plastids. Essential roles for FtsZ
      proteins in plastid division in land plants have been revealed. FtsZ forms the so
      called Z ring which, together with inner and outer plastid division rings, brings
      about constriction of the plastid. It has been shown that modulation of the
      expression level of FtsZ may result in altered chloroplast size and number. To
      test whether FtsZ is also involved in amyloplast division and whether this, in
      turn, may affect the starch granule size in crop plants, FtsZ protein levels were
      either reduced or increased in potato. As shown previously in other plant
      species, decreased StFtsZ1 protein levels in leaves resulted in a decrease in the
      number of chloroplasts in guard cells. More interestingly, plants with increased
      StFtsZ1 protein levels in tubers resulted in less, but larger, starch granules.
      This suggests that the stoichiometry between StFtsZ1 and other components of the
      plastid division machinery is important for its function. Starch from these
      tubers also had altered pasting properties and phosphate content. The importance
      of our results for the starch industry is discussed.

PMID- 17177792
TI  - Successful oral prime-immunization with VP60 from rabbit haemorrhagic disease
      virus produced in transgenic plants using different fusion strategies.
AB  - Expression levels of vaccine antigens in transgenic plants have important
      consequences in their use as edible vaccines. The major structural protein VP60
      from the rabbit haemorrhagic disease virus (RHDV) has been produced in transgenic
      plants using different strategies to compare its accumulation in plant tissues.
      The highest expressing plants were those presenting stable, complex, high-density
      structures formed by VP60, suggesting the importance of multisubunit structures
      for the stability of this protein in plant cells. Mice fed with leaves of
      transgenic plants expressing VP60 were primed to a subimmunogenic baculovirus
      derived vaccine single dose. This indicates that plants expressing VP60 antigen
      may be a new means for oral RHDV immunization.

PMID- 17177793
TI  - Plant cell wall biosynthesis: genetic, biochemical and functional genomics
      approaches to the identification of key genes.
AB  - Cell walls are dynamic structures that represent key determinants of overall
      plant form, plant growth and development, and the responses of plants to
      environmental and pathogen-induced stresses. Walls play centrally important roles
      in the quality and processing of plant-based foods for both human and animal
      consumption, and in the production of fibres during pulp and paper manufacture.
      In the future, wall material that constitutes the major proportion of cereal
      straws and other crop residues will find increasing application as a source of
      renewable fuel and composite manufacture. Although the chemical structures of
      most wall constituents have been defined in detail, the enzymes involved in their
      synthesis and remodelling remain largely undefined, particularly those involved
      in polysaccharide biosynthesis. There have been real recent advances in our
      understanding of cellulose biosynthesis in plants, but, with few exceptions, the
      identities and modes of action of polysaccharide synthases and other
      glycosyltransferases that mediate the biosynthesis of the major non-cellulosic
      wall polysaccharides are not known. Nevertheless, emerging functional genomics
      and molecular genetics technologies are now allowing us to re-examine the central
      questions related to wall biosynthesis. The availability of the rice, Populus
      trichocarpa and Arabidopsis genome sequences, a variety of mutant populations,
      high-density genetic maps for cereals and other industrially important plants,
      high-throughput genome and transcript analysis systems, extensive publicly
      available genomics resources and an increasing armoury of analysis systems for
      the definition of candidate gene function will together allow us to take a
      systems approach to the description of wall biosynthesis in plants.

PMID- 17177794
TI  - Synthesis of enzymatically active human alpha-L-iduronidase in Arabidopsis cgl
      (complex glycan-deficient) seeds.
AB  - As an initial step to develop plants as systems to produce enzymes for the
      treatment of lysosomal storage disorders, Arabidopsis thaliana wild-type (Col-0)
      plants were transformed with a construct to express human alpha-l-iduronidase
      (IDUA; EC 3.2.1.76) in seeds using the promoter and other regulatory sequences of
      the Phaseolus vulgaris arcelin 5-I gene. IDUA protein was easily detected on
      Western blots of extracts from the T(2) seeds, and extracts contained IDUA
      activity as high as 2.9 nmol 4-methylumbelliferone (4 MU)/min/mg total soluble
      protein (TSP), corresponding to approximately 0.06 microg IDUA/mg TSP. The
      purified protein reacted with an antibody specific for xylose-containing plant
      complex glycans, indicating its transit through the Golgi complex. In an attempt
      to avoid maturation of the N-linked glycans of IDUA, the same IDUA transgene was
      introduced into the Arabidopsis cgl background, which is deficient in the
      activity of N-acetylglucosaminyl transferase I (EC 2.4.1.101), the first enzyme
      in the pathway of complex glycan biosynthesis. IDUA activity and protein levels
      were significantly higher in transgenic cgl vs. wild-type seeds (e.g. maximum
      levels were 820 nmol 4 MU/min/mg TSP, or 18 microg IDUA/mg TSP). Affinity
      purified IDUA derived from cgl mutant seeds showed a markedly reduced reaction
      with the antibody specific for plant complex glycans, despite transit of the
      protein to the apoplast. Furthermore, gel mobility changes indicated that a
      greater proportion of its N-linked glycans were susceptible to digestion by
      Streptomyces endoglycosidase H, as compared to IDUA derived from seeds of wild
      type Arabidopsis plants. The combined results indicate that IDUA produced in cgl
      mutant seeds contains glycans primarily in the high-mannose form. This work
      clearly supports the viability of using plants for the production of human
      therapeutics with high-mannose glycans.

PMID- 17177795
TI  - A bipartite system for the constitutive and inducible expression of high levels
      of foreign proteins in plants.
AB  - We have developed combined transgene/virus vector systems for the expression of
      heterologous proteins in plants. The systems are based on the bipartite RNA plant
      virus, cowpea mosaic virus (CPMV), and involve the amplification of integrated
      copies of either full-length or deleted versions of RNA-2 carrying a foreign
      gene. In the case of plants transgenic for full-length versions of RNA-2 carrying
      the green fluorescent protein (GFP), amplification can be achieved by supplying
      RNA-1 either exogenously or by crossing. This allows either inducible or
      constitutive expression of the foreign gene and results in an infection that can
      be passaged to further plants. Replication of deleted versions of RNA-2
      harbouring GFP requires the presence of both RNA-1 and a suppressor of gene
      silencing, a function which we show can be supplied by HcPro from potato virus Y.
      Replication of the deleted versions of RNA-2 can be achieved by supplying the
      suppressor and RNA-1 either exogenously or by crossing, showing that this system
      can also be used in an inducible and constitutive format. The use of deleted
      forms of RNA-2 has the advantage that no infectious virus is produced, providing
      an effective method of biocontainment. The CPMV-based systems have advantages
      over existing plant expression systems in terms of the expression levels
      obtainable and the simplicity and flexibility of use, and should be of great
      practical benefit in the development of plants as bioreactors.

PMID- 17177796
TI  - HIV-1 p24-immunoglobulin fusion molecule: a new strategy for plant-based protein
      production.
AB  - We describe the engineering of a human immunodeficiency virus-1 (HIV-1) p24
      immunoglobulin A (IgA) antigen-antibody fusion molecule for therapeutic purposes
      and its enhancing effect on fused antigen expression in tobacco plants. Although
      many recombinant proteins have been expressed in transgenic plants as vaccine
      candidates, low levels of expression are a recurring problem. In this paper,
      using the HIV p24 core antigen as a model vaccine target, we describe a strategy
      for increasing the yield of a recombinant protein in plants. HIV p24 antigen was
      expressed as a genetic fusion with the alpha2 and alpha3 constant region
      sequences from human Ig alpha-chain and targeted to the endomembrane system. The
      expression of this fusion protein was detected at levels approximately 13-fold
      higher than HIV p24 expressed alone, and a difference in the behaviour of the two
      recombinant proteins during trafficking in the plant secretory pathway has been
      identified. Expressing the antigen within the context of alpha-chain Ig sequences
      resulted in the formation of homodimers and the antigen was correctly recognized
      by specific antibodies. Furthermore, the HIV p24 elicited T-cell and antibody
      responses in immunized mice. The use of Ig fusion partners is proposed as a
      generic platform technology for up-regulating the expression of antigens in
      plants, and may represent the first step in a strategy to design new vaccines
      with enhanced immunological properties.

PMID- 17177797
TI  - Transgene expression produced by biolistic-mediated, site-specific gene
      integration is consistently inherited by the subsequent generations.
AB  - The efficient production of stable transgenic plants is important for both crop
      improvement and functional genomics. Site-specific integration of foreign genes
      into a designated genomic position is an attractive tool for minimizing
      expression variability between transgenic lines. Here, we studied the utility of
      a Cre-mediated, site-specific integration approach, facilitated by particle
      bombardment, for streamlining the production of stable transgenic plants, using
      rice as a model species. Using this method, we generated 18 different transgenic
      lines containing a precise integration of a single copy of beta-glucuronidase
      gene (gusA) into a designated genomic location. Eleven of these lines contained
      no illegitimate integration in the background (single-copy lines), and seven
      contained illegitimate integrations in addition to the site-specific integration
      (multicopy lines). We monitored gusA expression in these lines up to three to
      four successive generations. Each of the single-copy lines expressed the gusA
      gene at consistent levels and nearly doubled the expression level in the
      homozygous state. In contrast, multicopy lines displayed expression variation and
      gene silencing. In about half of the multicopy lines, however, expression of the
      site-specific integration locus could be reactivated and stabilized on
      segregation of the illegitimate integrations, whereas, in the remaining half,
      expression could not be restored, as they contained genetically linked
      illegitimate integrations. This study demonstrates that biolistic-mediated, site
      specific gene integration is an efficient and reliable tool for streamlining the
      production of stable transgenic plants.

PMID- 17177798
TI  - Enhanced seed phytosterol accumulation through expression of a modified HMG-CoA
      reductase.
AB  - The regulation of phytosterol biosynthesis in seeds is of interest to
      biotechnologists because of the efficacy of dietary phytosterols in reducing
      blood cholesterol in humans. Mevalonate synthesis via 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (HMG-CoA reductase) is a key step in phytosterol
      biosynthesis. HMG-CoA reductase is inactivated by phosphorylation by SNF1-related
      protein kinase 1 (SnRK1). With the aim of increasing seed phytosterol levels,
      transgenic tobacco plants were produced expressing a full-length Arabidopsis
      (Arabidopsis thaliana) HMG-CoA reductase gene (HMG1) coding sequence, a modified
      HMG1 sequence encoding a protein lacking the target serine residue for
      phosphorylation by SnRK1, or a chimaeric sequence encoding the N-terminal domain
      of the Arabidopsis HMG1 enzyme fused with the catalytic domain of yeast HMG-CoA
      reductase, which lacks an SnRK1 target site. All three transgenes (35S-AtHMG1,
      35S-AtHMG1m and 35S-AtScHMG1) were under the control of a cauliflower mosaic
      virus 35S RNA promoter. Levels of seed phytosterols were up to 2.44-fold higher
      in plants transformed with the 35S-AtHMG1m gene than in the wild-type, and were
      significantly higher than in plants expressing 35S-AtHMG1 or 35S-AtScHMG1. In
      contrast, levels of phytosterols in leaves of plants transformed with the 35S
      AtHMG1m gene were unchanged, suggesting that regulation of HMG-CoA reductase by
      SnRK1 is an important factor in seeds but not in leaves. A total of 11
      independent transgenic lines expressing 35S-AtHMG1m or 35S-AtScHMG1 also showed
      an altered flower phenotype, comprising a compact floret, prolonged flowering,
      short, pale petals, a protruding style, short stamens, late anther development,
      little or no pollen production, premature flower abscission and poor seed set.
      Because of this phenotype, the modified HMG-CoA reductase gene would have to be
      expressed seed specifically if it were to be engineered into a crop plant for
      biotechnological purposes.

PMID- 17177800
TI  - Forcing single-chain variable fragment production in tobacco seeds by fusion to
      elastin-like polypeptides.
AB  - Single-chain variable fragments (scFvs), as well as other recombinant antibodies,
      have become powerful tools for therapy and analysis in both human and veterinary
      medicine. Transgenic plants have been developed as an efficient production system
      for these recombinant proteins, achieving high yields at moderate cost. Seeds are
      especially useful organs for molecular farming because of their high protein
      content and their ability to keep proteins functional during extended storage in
      ambient conditions. Several concepts have been applied to optimize protein
      accumulation in seeds, such as the use of specific promoters and transcription
      enhancers. In this paper, we present a new strategy to enhance substantially the
      expression of scFvs in transgenic tobacco seeds, based on C-terminal fusions to
      elastin-like polypeptides (ELPs). This strategy resulted in a 40-fold increase in
      scFv accumulation, with levels approaching 25% of total soluble protein. The
      fusion proteins show specific activities and affinities comparable with the
      properties of the corresponding scFvs. This strategy thus opens up new ways to
      improve greatly the production of recombinant antibodies in plant seeds.

PMID- 17177799
TI  - Design of tomato fruits with reduced allergenicity by dsRNAi-mediated inhibition
      of ns-LTP (Lyc e 3) expression.
AB  - Plant genetic engineering has the potential to introduce new allergenic proteins
      into foods but, at the same time, it can be used to remove established allergens.
      Here, we report the molecular characterization of Lyc e 3, a new tomato
      (Lycopersicon esculentum) allergen, and the efficient down-regulation of its
      expression in transgenic tomato plants. Following the identification of an
      immunoglobulin E (IgE)-binding 9-kDa polypeptide in tomato peel, designated Lyc e
      3, its partial amino acid sequence was determined by N-terminal protein
      sequencing. Sequence comparison revealed that Lyc e 3 encodes a nonspecific lipid
      transfer protein (ns-LTP). In plants, ns-LTPs are encoded by large gene families
      which differ in primary amino acid sequence, expression and proposed cellular
      function. To identify Lyc e 3 encoding complementary DNAs (cDNAs), public tomato
      expressed sequence tag (EST) databases were screened for ns-LTP sequences.
      Following this strategy, two cDNAs, LTPG1 and LTPG2, with high homology to the N
      terminal sequence of Lyc e 3, were identified. Ectopic expression of LTPG1 and
      LTPG2 in Escherichia coli, followed by immunoblotting, verified their IgE
      reactivity. Subsequently, transgenic tomato plants constitutively expressing
      LTPG1- or LTPG2-specific double-stranded RNA interference (dsRNAi) constructs
      were created and tested for the suppression of Lyc e 3 accumulation. Efficient
      silencing of Lyc e 3 was documented by Northern and Western blotting. In both
      cases, Lyc e 3 accumulation was decreased to levels below the detection limit
      (less than 0.5% of the wild-type protein). The allergenic potential of Lyc e 3
      deficient tomato fruits was tested by measuring histamine release from sensitized
      human basophils stimulated with transgenic and parental lines. These assays
      revealed a strong (10- to 100-fold) decrease in histamine release of human
      basophils challenged with transgenic fruit extracts when compared with control
      extracts. These results demonstrate the feasibility of creating low allergenic
      tomato fruits by means of dsRNAi inhibition.

PMID- 17177801
TI  - Genetic transformation of barley (Hordeum vulgare L.) via infection of
      androgenetic pollen cultures with Agrobacterium tumefaciens.
AB  - A novel genetic transformation method for barley (Hordeum vulgare L.), based on
      infection of androgenetic pollen cultures with Agrobacterium tumefaciens, is
      presented. Winter-type barley cv. 'Igri' was amenable to stable integration of
      transgenes mediated by A. tumefaciens strain LBA4404 harbouring a vector system
      that confers hypervirulence, or by the non-hypervirulent strain GV3101 with a
      standard binary vector. The efficacy of gene transfer was substantially
      influenced by pollen pre-culture time, choice of Agrobacterium strain and vector
      system, Agrobacterium population density, medium pH and the concentrations of
      acetosyringone, CaCl(2) and glutamine. After co-culture, rapid removal of viable
      agrobacteria was crucial for subsequent development of the pollen culture. To
      this end, the growth of agrobacteria was suppressed by the concerted effects of
      appropriate antibiotics, low pH, reduced level of glutamine and high
      concentrations of CaCl(2) and acetosyringone. Following infection with LBA4404
      and GV3101, about 31% and 69%, respectively, of the primary transgenic (T(0))
      plants carried a single copy of the sequence integrated. The use of hypervirulent
      A. tumefaciens and hygromycin resistance as a selectable marker resulted in 3.7
      T(0) plants per donor spike. About 60% of the primary transgenic plants set seed,
      indicating spontaneous genome doubling. An analysis of 20 T(1) populations
      revealed that four progenies did not segregate for reporter gene expression. This
      indicates that the approach pursued enables the generation of instantly
      homozygous primary transgenic plants. The method established will be a valuable
      tool in functional genomics as well as for the biotechnological improvement of
      barley.

PMID- 17177802
TI  - Characterization of a higher plant herbicide-resistant phytoene desaturase and
      its use as a selectable marker.
AB  - Three natural somatic mutations at codon 304 of the phytoene desaturase gene
      (pds) of Hydrilla verticillata (L. f. Royle) have been reported to provide
      resistance to the herbicide fluridone. We substituted the arginine 304 present in
      the wild-type H. verticillata phytoene desaturase (PDS) with all 19 other natural
      amino acids and tested PDS against fluridone. In in vitro assays, the threonine
      (Thr), cysteine (Cys), alanine (Ala) and glutamine (Gln) mutations imparted the
      highest resistance to fluridone. Thr, the three natural mutations [Cys, serine
      (Ser), histidine (His)] and the wild-type PDS protein were tested in vitro
      against seven inhibitors of PDS representing several classes of herbicides. These
      mutations conferred cross-resistance to norflurazon and overall negative cross
      resistance to beflubutamid, picolinafen and diflufenican. The T3 generation of
      transgenic Arabidopsis thaliana plants harbouring the four selected mutations and
      wild-type pds had similar patterns of cross-resistance to the herbicides as
      observed in the in vitro assays. The Thr304 Hydrilla pds mutant proved to be an
      excellent marker for the selection of transgenic plants. Seedlings harbouring
      Thr304 pds had a maximum resistance to sensitivity (R/S) ratio of 57 and 14 times
      higher than that of the wild-type for treatments with norflurazon and fluridone,
      respectively. These plants exhibited normal growth and development, even after
      long-term exposure to herbicide. As Thr304 pds is of plant origin, it could
      become more acceptable than other selectable markers for use in genetically
      modified food.

PMID- 17177803
TI  - Transgenesis has less impact on the transcriptome of wheat grain than
      conventional breeding.
AB  - Detailed global gene expression profiles have been obtained for a series of
      transgenic and conventionally bred wheat lines expressing additional genes
      encoding HMW (high molecular weight) subunits of glutenin, a group of endosperm
      specific seed storage proteins known to determine dough strength and therefore
      bread-making quality. Differences in endosperm and leaf transcriptome profiles
      between untransformed and derived transgenic lines were consistently extremely
      small, when analysing plants containing either transgenes only, or also marker
      genes. Differences observed in gene expression in the endosperm between
      conventionally bred material were much larger in comparison to differences
      between transgenic and untransformed lines exhibiting the same complements of
      gluten subunits. These results suggest that the presence of the transgenes did
      not significantly alter gene expression and that, at this level of investigation,
      transgenic plants could be considered substantially equivalent to untransformed
      parental lines.

PMID- 17177804
TI  - A metabolomic study of substantial equivalence of field-grown genetically
      modified wheat.
AB  - The 'substantial equivalence' of three transgenic wheats expressing additional
      high-molecular-weight subunit genes and the corresponding parental lines (two
      lines plus a null transformant) was examined using metabolite profiling of
      samples grown in replicate field trials on two UK sites (Rothamsted,
      Hertfordshire and Long Ashton, near Bristol) for 3 years. Multivariate comparison
      of the proton nuclear magnetic resonance spectra of polar metabolites extracted
      with deuterated methanol-water showed a stronger influence of site and year than
      of genotype. Nevertheless, some separation between the transgenic and parental
      lines was observed, notably between the transgenic line B73-6-1 (which had the
      highest level of transgene expression) and its parental line L88-6. Comparison of
      the spectra showed that this separation resulted from increased levels of maltose
      and/or sucrose in this transgenic line, and that differences in free amino acids
      were also apparent. More detailed studies of the amino acid composition of
      material grown in 2000 were carried out using gas chromatography-mass
      spectrometry. The most noticeable difference was that the samples grown at
      Rothamsted consistently contained larger amounts of acidic amino acids (glutamic,
      aspartic) and their amides (glutamine, asparagine). In addition, the related
      lines, L88-6 and B73-6-1, both contained larger amounts of proline and gamma
      aminobutyric acid when grown at Long Ashton than at Rothamsted. The results
      clearly demonstrate that the environment affects the metabolome and that any
      differences between the control and transgenic lines are generally within the
      same range as the differences observed between the control lines grown on
      different sites and in different years.

PMID- 17177805
TI  - Proliferative phase endosperm promoters from Arabidopsis thaliana.
AB  - Endosperm accounts for a large proportion of human nutrition and is also a major
      determinant of seed viability and size, not only in cereals, but also in species
      with ephemeral endosperms, such as soybean and oilseed rape. The extent of
      endosperm proliferation early in seed development is a crucial component in
      setting seed size; therefore, a biotechnological approach for the modification of
      this trait requires promoters active in early endosperm. To find such promoters,
      we constructed an array based on cDNAs extracted from developing Arabidopsis
      seeds enriched for proliferating endosperm. Hybridization with RNA extracted from
      vegetative and reproductive tissues, including endosperm, and subsequent data
      filtering yielded sets of endosperm-expressed and endosperm-preferred genes,
      including many hundreds not previously identified in array experiments designed
      to detect genes expressed in Arabidopsis seeds. Of eight promoters selected for
      validation, seven were active in early endosperm, three with no detected activity
      elsewhere in the plant. Therefore, this strategy has yielded proliferative phase
      endosperm promoters which should be useful in altering seed size.

PMID- 17177806
TI  - Production of high-starch, low-glucose potatoes through over-expression of the
      metabolic regulator SnRK1.
AB  - Transgenic potato (Solanum tuberosum cv. Prairie) lines were produced over
      expressing a sucrose non-fermenting-1-related protein kinase-1 gene (SnRK1) under
      the control of a patatin (tuber-specific) promoter. SnRK1 activity in the tubers
      of three independent transgenic lines was increased by 55%-167% compared with
      that in the wild-type. Glucose levels were decreased, at 17%-56% of the levels of
      the wild-type, and the starch content showed an increase of 23%-30%. Sucrose and
      fructose levels in the tubers of the transgenic plants did not show a significant
      change. Northern analyses of genes encoding sucrose synthase and ADP-glucose
      pyrophosphorylase, two key enzymes involved in the biosynthetic pathway from
      sucrose to starch, showed that the expression of both was increased in tubers of
      the transgenic lines compared with the wild-type. In contrast, the expression of
      genes encoding two other enzymes of carbohydrate metabolism, alpha-amylase and
      sucrose phosphate synthase, showed no change. The activity of sucrose synthase
      and ADP-glucose pyrophosphorylase was also increased, by approximately 20%-60%
      and three- to five-fold, respectively, whereas the activity of hexokinase was
      unchanged. The results are consistent with a role for SnRK1 in regulating carbon
      flux through the storage pathway to starch biosynthesis. They emphasize the
      importance of SnRK1 in the regulation of carbohydrate metabolism and resource
      partitioning, and indicate a specific role for SnRK1 in the control of starch
      accumulation in potato tubers.

PMID- 17177807
TI  - Tomato is a highly effective vehicle for expression and oral immunization with
      Norwalk virus capsid protein.
AB  - Norwalk virus (NV) is an important agent of epidemic gastroenteritis, and an oral
      subunit vaccine shows potential for protection. Recombinant Norwalk virus (rNV)
      capsid protein expressed in plants assembles virus-like particles (VLPs) that are
      orally immunogenic in mice and humans. In this article we examine rNV expression
      in tomato and potato using a plant-optimized gene, and test the immunogenicity of
      dried tomato fruit and potato tuber fed to mice. The synthetic gene increased rNV
      expression fourfold in tomato and potato plants, which assembled VLP. Four doses
      of 0.4 g freeze-dried tomato fruit containing 64 microg rNV (40 microg VLPs)
      induced NV-specific serum IgG and mucosal IgA in > or = 80% of mice, while doses
      of 0.8 g elicited systemic and mucosal antibody responses in all mice. Feedings
      of 1 g freeze-dried potato tuber containing 120 microg rNV (90 microg VLPs) were
      required to produce 100% responsiveness. Oxidation of phenolic compounds upon
      rehydration of dried tuber caused significant VLP instability, thus decreasing
      immunogenicity. Air-dried tomato fruit stimulated stronger immune responses than
      freeze-dried fruit of the same mass, perhaps by limiting the destruction of plant
      cell matrix and membrane systems that occurs with freeze-drying. Thus, rNV in
      dried transgenic tomato fruit was a more potent immunogen than that in dried
      potato tubers, based on the total VLPs ingested. These findings support the use
      of stabilized, dried tomato fruit for oral delivery of subunit vaccines.

PMID- 17177808
TI  - Pathway engineering for healthy phytochemicals leading to the production of novel
      flavonoids in tomato fruit.
AB  - Flavonoids are a large family of plant polyphenolic secondary metabolites.
      Although they are widespread throughout the plant kingdom, some flavonoid classes
      are specific for only a few plant species. Due to their presumed health benefits
      there is growing interest in the development of food crops with tailor-made
      levels and composition of flavonoids, designed to exert an optimal biological
      effect. In order to explore the possibilities of flavonoid engineering in tomato
      fruits, we have targeted this pathway towards classes of potentially healthy
      flavonoids which are novel for tomato. Using structural flavonoid genes (encoding
      stilbene synthase, chalcone synthase, chalcone reductase, chalcone isomerase and
      flavone synthase) from different plant sources, we were able to produce
      transgenic tomatoes accumulating new phytochemicals. Biochemical analysis showed
      that the fruit peel contained high levels of stilbenes (resveratrol and piceid),
      deoxychalcones (butein and isoliquiritigenin), flavones (luteolin-7-glucoside and
      luteolin aglycon) and flavonols (quercetin glycosides and kaempferol glycosides).
      Using an online high-performance liquid chromatography (HPLC) antioxidant
      detection system, we demonstrated that, due to the presence of the novel
      flavonoids, the transgenic tomato fruits displayed altered antioxidant profiles.
      In addition, total antioxidant capacity of tomato fruit peel with high levels of
      flavones and flavonols increased more than threefold. These results on genetic
      engineering of flavonoids in tomato fruit demonstrate the possibilities to change
      the levels and composition of health-related polyphenols in a crop plant and
      provide more insight in the genetic and biochemical regulation of the flavonoid
      pathway within this worldwide important vegetable.

PMID- 17177809
TI  - Directed microspore-specific recombination of transgenic alleles to prevent
      pollen-mediated transmission of transgenes.
AB  - A major challenge for future genetically modified (GM) crops is to prevent
      undesired gene flow of transgenes to plant material intended for another use.
      Recombinase-mediated auto excision of transgenes directed by a tightly controlled
      microspore-specific promoter allows efficient removal of either the selectable
      marker gene or of all introduced transgenes during microsporogenesis. This way,
      transgene removal becomes an integral part of the biology of pollen maturation,
      not requiring any external stimulus such as chemical induction by spraying. We
      here show the feasibility of engineering transgenic plants to produce pollen
      devoid of any transgene. Highly efficient excision of transgenes from tobacco
      pollen was achieved with a potential failure rate of at most two out of 16,800
      seeds (0.024%). No evidence for either premature activation or absence of
      activation of the recombinase system was observed under stress conditions in the
      laboratory. This approach can prevent adventitious presence of transgenes in non
      GM crops or related wild species by gene flow. Such biological containment may
      help the deployment and management of coexistence practices to support consumer
      choice and will promote clean molecular farming for the production of high-value
      compounds in plants.

PMID- 17177810
TI  - Genetic modification of cassava for enhanced starch production.
AB  - To date, transgenic approaches to biofortify subsistence crops have been rather
      limited. This is particularly true for the starchy root crop cassava (Manihot
      esculenta Crantz). Cassava has one of the highest rates of CO(2) fixation and
      sucrose synthesis for any C3 plant, but rarely reaches its yield potentials in
      the field. It was our hypothesis that starch production in cassava tuberous roots
      could be increased substantially by increasing the sink strength for
      carbohydrate. To test this hypothesis, we generated transgenic plants with
      enhanced tuberous root ADP-glucose pyrophosphorylase (AGPase) activity. This was
      achieved by expressing a modified form of the bacterial glgC gene under the
      control of a Class I patatin promoter. AGPase catalyses the rate-limiting step in
      starch biosynthesis, and therefore the expression of a more active bacterial form
      of the enzyme was expected to lead to increased starch production. To facilitate
      maximal AGPase activity, we modified the Escherichia coli glgC gene (encoding
      AGPase) by site-directed mutagenesis (G336D) to reduce allosteric feedback
      regulation by fructose-1,6-bisphosphate. Transgenic plants (three) expressing the
      glgC gene had up to 70% higher AGPase activity than control plants when assayed
      under conditions optimal for plant and not bacterial AGPase activity. Plants
      having the highest AGPase activities had up to a 2.6-fold increase in total
      tuberous root biomass when grown under glasshouse conditions. In addition, plants
      with the highest tuberous root AGPase activity had significant increases in above
      ground biomass, consistent with a possible reduction in feedback inhibition on
      photosynthetic carbon fixation. These results demonstrate that targeted
      modification of enzymes regulating source-sink relationships in crop plants
      having high carbohydrate source strengths is an effective strategy for increasing
      carbohydrate yields in sink tissues.

PMID- 17177812
TI  - A time to integrate the complete wound team: from bench to bedside and beyond.

PMID- 17177811
TI  - Marker-free transgenic (MFT) near-isogenic introgression lines (NIILs) of
      'golden' indica rice (cv. IR64) with accumulation of provitamin A in the
      endosperm tissue.
AB  - We have developed near-isogenic introgression lines (NIILs) of an elite indica
      rice cultivar (IR64) with the genes for beta-carotene biosynthesis from dihaploid
      (DH) derivatives of golden japonica rice (cv. T309). A careful analysis of the DH
      lines indicated the integration of the genes of interest [phytoene synthase (psy)
      and phytoene desaturase (crtI)] and the selectable marker gene (hygromycin
      phosphotransferase, hph) in two unlinked loci. During subsequent crossing,
      progenies could be obtained carrying only the locus with psy and crtI, which was
      segregated independently from the locus containing the hph gene during meiotic
      segregation. The NIILs (BC(2)F(2)) showed maximum similarity with the recurrent
      parent cultivar IR64. Further, progenies of two NIILs were devoid of any
      fragments beyond the left or right border, including the chloramphenicol
      acetyltransferase (cat) antibiotic resistance gene of the transformation vector.
      Spectrophotometric readings showed the accumulation of up to 1.06 microg total
      carotenoids, including beta-carotene, in 1 g of the endosperm. The accumulation
      of beta-carotene was also evident from the clearly visible yellow colour of the
      polished seeds.

PMID- 17177813
TI  - Getting to mammalian wound repair and amphibian limb regeneration: a mechanistic
      link in the early events.

PMID- 17177814
TI  - Regulation of wound healing from a connective tissue perspective.
AB  - Tissue injury resulting in irreversible tissue loss initiates the repair process.
      The restoration of dermal loss is by scarring, where a new cell population
      resides in a new connective tissue matrix. The chemical composition of a scar is
      similar to normal dermis, but the organization of that tissue is altered. The
      inability of the organism to reassemble collagen into a normal dermal pattern is
      an attribute of a scar, but in most cases it restores normal function. With
      impaired scarring, wound dehiscence or chronic wounds arise, whereas the
      overproduction of scar tissue results in keloid or hypertrophic scarring. In both
      situations a catastrophic end point occurs. The volume of scar tissue deposited,
      as well as its organization, is critical for determining the scar's integrity,
      stability, and restoration of function. The maturation of scar depends on the
      character of its resident cell populations, the quality of deposited connective
      tissue, and the interactions between those components. In this Perspective
      article, the focus will be on the repair process in terms of collagen fiber
      organization. As our knowledge of cell-cell and cell-matrix interactions in the
      repair process increases, we may be able to direct the pattern of scar collagen
      fibers to resemble that of dermis and thereby provide better wound care to the
      patient of the future.

PMID- 17177815
TI  - Differential effects of oxygen on human dermal fibroblasts: acute versus chronic
      hypoxia.
AB  - The observation that many chronic wounds are ischemic has spurred a series of
      studies evaluating the response of cells exposed to hypoxia. To date, these
      studies have shown largely beneficial effects from hypoxia, such as increased
      cellular replication and procollagen synthesis. These findings are counter
      intuitive from a clinical standpoint because cellular growth and synthetic
      function are known to be retarded in chronic ischemic wounds. We have established
      an in vitro system in which human dermal fibroblasts grown chronically at 5 +/- 3
      mm Hg will proliferate at a rate three times slower than those fibroblasts grown
      under standard culture conditions (namely an oxygen partial pressure of 150 mm
      Hg). No phenotypic changes are noted in chronically hypoxic cells, and the growth
      retarding effects are reversible when the cells are returned to standard oxygen
      conditions. Competitive reverse transcription-polymerase chain reaction showed
      that acute exposure to hypoxia (up to 1 week) results in a 6.3-fold increase in
      the relative expression of transforming growth factor-beta1 messenger RNA,
      whereas chronic exposure to hypoxia leads to a 3.1-fold decrease in this message.
      Collagen production measured at both the mRNA and protein level is also decreased
      in the setting of chronic hypoxia. We propose that this system may be the most
      appropriate setting for studying the role of oxygen on dermal fibroblasts in
      ischemic, nonhealing wounds.

PMID- 17177816
TI  - Differential expression of platelet-derived growth factor receptor-beta in an
      aging model of wound repair.
AB  - Impaired wound healing as a result of age is a well-documented phenomenon.
      However, the overall deficit in healing is substantially increased when the
      healing wound of an aged animal is ischemic. We hypothesized that both of these
      deficits are cytokine mediated. We have studied the messenger RNA expression of
      platelet-derived growth factor receptor-beta, using the rabbit dermal ulcer model
      of wound repair, in young (3 to 6 months) and aged (48 months and 60 months)
      rabbits under normal and ischemic conditions. Platelet-derived growth factor
      receptor-beta mRNA expression was measured with the use of quantitative reverse
      transcriptase-polymerase chain reaction with incorporation of a synthetic,
      nonhomologous DNA fragment complementary to platelet-derived growth factor
      receptor-beta primers as a competitive internal standard. Results in young
      rabbits showed a large upregulation of platelet-derived growth factor receptor
      beta mRNA expression after wounding. In both aged animal groups, platelet-derived
      growth factor receptor-beta expression was found to be significantly decreased in
      nonischemic wounds relative to young nonischemic controls. Ischemia was found to
      have little effect on platelet-derived growth factor receptor-beta mRNA
      expression in young animals relative to matched controls. However, ischemia
      induced a large decrease in the platelet-derived growth factor receptor-beta mRNA
      levels of wounds of aged animals relative to paired aged nonischemic wounds.
      Results suggest an age-related delay in platelet-derived growth factor receptor
      beta mRNA expression in healing wounds, as well as an age-related decline in
      responsiveness to confounding ischemia.

PMID- 17177817
TI  - Transcutaneous oxygen measurements predict healing of leg wounds with hyperbaric
      therapy.
AB  - Twenty-six patients with chronic leg wounds had transcutaneous oxygen
      measurements taken from the peri-wound area and a chest reference site before
      undergoing hyperbaric oxygen therapy in order to evaluate the utility of
      transcutaneous oxygen measurements in predicting the response of wounds to
      hyperbaric therapy. Wound scores and wound areas were determined before treatment
      and after 10 hyperbaric exposures. Patients whose wounds averaged a 5% or greater
      reduction in wound score per treatment were designated "responders." Nine
      patients' wounds exhibited at least a 5% reduction in wound score per treatment.
      There were no differences observed between responders and the 17 nonresponders in
      age, duration of the wound, initial wound area, initial wound score, or in wound
      or reference transcutaneous oxygen measurements. Responders required
      significantly fewer treatments to achieve wound closure than did nonresponders.
      Peri-wound transcutaneous oxygen pressure when the patient was exposed to 2.4
      atmospheres absolute correlated directly with the improvement in wound score per
      treatment (r = 0.64, p = 0.03). An inverse correlation was noted between surface
      peri-wound transcutaneous oxygen pressure and improvement in wound score per
      treatment (r = -0.74, p = 0.006). Elevated peri-wound transcutaneous oxygen
      measurements at 2.4 atmospheres absolute and reduced peri-wound oxygen
      measurements at 1 atmosphere absolute were associated with a more rapid response
      to hyperbaric oxygen treatments in patients with chronic leg wounds. The use of
      these measurements should allow this expensive and time-consuming therapy to be
      limited to those patients most likely to benefit.

PMID- 17177818
TI  - Recurrence rate of diabetic neurotrophic foot ulcers healed using topical
      application of growth factors released from platelets.
AB  - The purpose of this study was to determine the recurrence rate of diabetic
      neurotrophic foot ulcers that had healed in a treatment protocol using topically
      applied growth factors released from platelets. Thirty-six patients with diabetic
      neurotrophic foot ulcers were entered into a randomized prospective double-blind
      20-week trial of topically applied platelet growth factors or buffered saline
      dressings. Ulcers had been present for 15.5 months (mean, range 2 to 60 months).
      Sixteen patients (44%) healed and were followed up for as many as 30 months to
      determine the rate of ulcer recurrence. Eleven patients (68.8%) had ulcers that
      recurred, including 10 treated with platelet growth factors and one treated with
      buffered saline solution. These ulcers had been present for 20 months (range 5 to
      60 months) before healing. Average time to ulcer recurrence was 2.2 months (range
      0.25 to 7 months). Five ulcers (31.2%) remained healed, including four treated
      with platelet growth factors and one treated with buffered saline solution. These
      healed, nonrecurring ulcers had been present for 5 months (range 2 to 6 months)
      before healing. Average follow up was 25 months (range 24 to 30 months). Ulcers
      were more likely to recur if they had been present longer before healing. If
      patients were not compliant in wearing footwear to protect the healed ulcer, the
      ulcers were prone to early recurrence. These data indicate that ulcers healed by
      using growth factors in the form of a platelet growth factors did not have more
      durable skin over the ulcer and were prone to early ulcer recurrence.

PMID- 17177819
TI  - Biochemical analysis of wound fluid from nonhealing and healing chronic leg
      ulcers.
AB  - The purpose of this study was to determine the biochemical composition of fluid
      taken from chronic wounds, to compare these values with that of serum, and
      therefore to assess whether the wound fluid is representative of the
      extracellular environment of the wound. Paired wound fluid and blood samples were
      collected from eight patients with chronic leg ulcers in a nonhealing and healing
      phase. Wound fluid and serum samples were screened for a profile of general
      biochemical analyses, including electrolytes, lactate, glucose, and protein
      analyses. Electrolyte levels were essentially identical in wound fluid and serum
      samples. Lactate and lactate dehydrogenase levels were significantly greater and
      glucose and bicarbonate levels were significantly lower in wound fluid when
      compared with the paired serum samples. Albumin and total protein levels in wound
      fluid were on average half those of serum levels. In this small sample of eight
      patients, wound fluid collected from chronic leg ulcers is an exudate with the
      biochemical composition expected in extracellular fluid. In addition, bicarbonate
      and glucose levels increase and C-reactive protein levels decrease in wound
      fluid, but remain unchanged in serum, during healing. These results suggest
      changes in the state of hypoxia and the inflammatory process in the healing
      wound.

PMID- 17177820
TI  - Histochemical analysis of growth factor, fibronectin, and iron content of sickle
      cell leg ulcers.
AB  - To better understand the pathogenesis and slow healing of sickle cell leg ulcers,
      we analyzed tissues for their content of iron and their immunohistochemical level
      of basic fibroblast growth factor, transforming growth factor-beta, and
      fibronectin. Debrided leg ulcer tissue from seven patients with sickle cell
      anemia were used. All sections stained strongly for basic fibroblast growth
      factor. The reactions to iron and fibronectin were variable (trace to 4+, 0 to
      3+, respectively), and there was weak or negative immunohistochemical staining
      for transforming growth factor-beta. These findings suggest the possibility that
      iron and/or a low content of transforming growth factor-beta and fibronectin may
      play a role in the chronicity of these lesions. Conversely, reducing tissue iron
      and/or applying transforming growth factor-beta or fibronectin topically may
      promote the healing of sickle cell leg ulcers.

PMID- 17177821
TI  - Covering by a flap induces apoptosis of granulation tissue myofibroblasts and
      vascular cells.
AB  - It has recently been shown that during the healing of an open wound, apoptosis
      mediates the decrease in cellularity during the transition between granulation
      tissue and scar. Because reduced contraction and a decrease in the number of
      fibroblastic cells have been described in wounds covered with a successful skin
      graft, we hypothesized that apoptosis could be responsible for these phenomena.
      Using in situ labeling of fragmented DNA, immunohistochemistry for alpha-smooth
      muscle actin, and electron microscopy, we have studied in rats the evolution of
      10-day-old wound tissue covered with a total skin flap (containing epidermis,
      dermis, and the cutaneous muscle). In 10-day-old wound tissue, few apoptotic
      vascular cells and rare apoptotic myofibroblasts were present; the number of
      apoptotic cells increased slightly 72 hours later. In wounds covered with total
      skin flaps, the number of apoptotic vascular and myofibroblastic cells increased
      drastically 6 hours after flap application with a maximum at 24 and 48 hours,
      respectively. A decrease of apoptotic cell number was noted at 72 hours; at this
      time, the size of the granulation tissue was greatly reduced and showed
      extracellular matrix remodeling. Total flaps were more efficient in the induction
      of granulation tissue cell apoptosis compared with dermo-epidermal flaps.
      Moreover, the control application of full-thickness skin autografts, which were
      not viable 7 days later, did not induce apoptosis 24 hours after implantation.
      Our results indicate that covering granulation tissue with a skin flap results in
      a massive apoptotic process, possibly by means of a (some) locally released
      substance(s).

PMID- 17177822
TI  - Local induction of an insulin-like growth factor binding protein-3 degrading
      protease activity in the course of wound healing.
AB  - Proteases that reduce insulin-like growth factor binding protein-3 affinity for
      insulin-like growth factor-I have been found in various biological fluids from
      human beings and rats. The aim of this study was to assess the local and systemic
      role of insulin-like growth factor binding protein-3 proteases in the course of
      wound healing. Six rats had polyvinyl alcohol sponges implanted subcutaneously.
      Wound fluid and serum were collected 3 days after wounding. Gel filtration
      experiments showed that insulin-like growth factor-I was present as a 150 kDa
      complex in both serum and wound fluid. However, insulin-like growth factor
      binding protein-3 measured by Western ligand blotting was virtually absent in
      wound fluid. Co-incubation of serum and wound fluid resulted in an
      ethylenediamine tetraacetic acid-inhibitable degradation of serum insulin-like
      growth factor binding protein-3, suggesting the presence of an insulin-like
      growth factor binding protein-3 degrading activity in wound fluid. Incubation of
      ((125)I)-labeled insulin-like growth factor binding protein-3 in wound fluid and
      serum showed a rapid and time-dependent proteolysis of insulin-like growth factor
      binding protein-3 in wound fluid with metabolites similar to those generated by
      human term pregnant serum. No sign of insulin-like growth factor binding protein
      3 degrading activity was observed in rat-serum. In conclusion, there is an
      insulin-like growth factor binding protein-3 proteolytic activity in wound fluid,
      and it is hypothesized that this activity results in a localized increase in
      insulin-like growth factor-I bioactivity.

PMID- 17177823
TI  - Transforming growth factor type e is a novel mediator of wound repair.
AB  - Transforming growth factor type e is a potent mitogen for epithelial and
      fibroblastic cells in vitro. It is primarily produced by epithelial tissues and
      cells, including normal skin keratinocytes. In this study we examined the effects
      of transforming growth factor type e in vivo and in vitro. On application of
      transforming growth factor type e to the chorioallantoic membrane of 8-day-old
      chick embryos, we noted a prominent thickening of the membrane caused primarily
      by fibroblastic and epithelial proliferation. In a subsequent study, transforming
      growth factor type e suspended in Matrigel was injected subcutaneously into the
      abdominal wall of Swiss National Institutes of Health mice. Significant influx of
      first neutrophils and then macrophages into the gel of transforming growth factor
      type e-treated mice, but not of control mice, was observed. Transforming growth
      factor type e also exhibited a potent chemoattractive effect on the J774
      macrophage cell line in vitro. In transcutaneous mouse wounds, topical
      administration of transforming growth factor type e led first to an influx of
      neutrophils and macrophages, followed by an increased formation of granulation
      tissue in the transforming growth factor type e-treated wounds. These results
      suggest that transforming growth factor type e plays an important role in wound
      healing as a chemoattractant for neutrophils and macrophages and as a mitogen for
      epithelial and fibroblastic cells.

PMID- 17177824
TI  - Effects of transforming growth factor-beta1 on extracellular matrix gene
      expression by human fibroblasts from a laryngeal stenotic lesion.
AB  - Transforming growth factor-beta1 appears to play important roles in normal wound
      healing by increasing synthesis of extracellular matrix components. However, the
      role of transforming growth factor-beta1 in the production of excessive scar
      tissue by fibroblasts from stenotic lesions of the larynx has not been evaluated.
      We examined the effect of transforming growth factor-beta1 on the steady-state
      messenger RNA levels of elastin, alpha2(l) procollagen, and lysyl oxidase (the
      enzyme that cross-links both of these structural proteins) in cell cultures of
      diploid human fibroblasts established from fetal skin, newborn foreskin, and an
      adult laryngeal stenotic lesion. Time-course and dose-response experiments
      demonstrated that treatment with 500 pmol/L transforming growth factor-beta1 for
      20 hours induced maximal levels of mRNA for elastin (7- to 59-fold) and alpha2(l)
      procollagen (1.7- to 2.4-fold) in all three cultures of fibroblasts. Transforming
      growth factor-beta1 also increased levels of lysyl oxidase mRNA in fibroblasts
      cultured from newborn foreskin (2.4-fold) and a stenotic lesion (10-fold) but had
      minimal effects on the fibroblasts cultured from fetal skin (1.1-fold), which
      constitutively expressed high levels of lysyl oxidase mRNA. Furthermore, the
      fibroblast culture established from a laryngeal stenotic lesion responded with
      the highest fold-induction for all three mRNAs. Inhibition of mRNA synthesis by
      actinomycin D showed that transcription was required for transforming growth
      factor-beta1 induction of elastin, alpha2(l) procollagen, and lysyl oxidase mRNA
      in all three cultures of fibroblasts. Inhibition of protein synthesis by
      cycloheximide showed that translation was required for maximal induction by
      transforming growth factor-beta1 of elastin mRNA but had no observable effect on
      alpha2(l) procollagen mRNA in all three cultures of fibroblasts. In addition,
      translation was required for maximal induction of the lysyl oxidase mRNA by
      transforming growth factor-beta1 in the fibroblasts cultured from a stenotic
      lesion but not for fibroblast cultures established from fetal and adult skin.
      These results show that transforming growth factor-beta1 coordinately increases
      mRNA levels for the structural extracellular matrix proteins collagen and
      elastin, as well as for the cross-linking enzyme, lysyl oxidase. These data also
      support the hypothesis that transforming growth factor-beta1 may contribute to
      the formation of laryngeal stenotic lesions.

PMID- 17177825
TI  - Modulation of alpha-smooth muscle actin expression in fibroblasts by transforming
      growth factor-beta isoforms: an in vivo and in vitro study.
AB  - Myofibroblasts are granulation tissue fibroblasts bearing ultrastructural and
      biochemical features of smooth muscle cells, such as cytoplasmic microfilaments
      and alpha-smooth muscle actin expression. They appear transiently during wound
      healing and more permanently during several pathologic situations such as
      fibrotic diseases. Transforming growth factor-beta1 has been suggested to be an
      important promoter of the myofibroblastic phenotype. Here we show that (1)
      transforming growth factor-beta2, like transforming growth factor-beta1, induces
      myofibroblast formation in vivo and in vitro; (2) transforming growth factor
      beta3 acts as a negative regulator of the myofibroblastic phenotype in vivo but
      not in vitro; and (3) in vitro, the three different transforming growth factor
      beta isoforms are equally able to induce alpha-smooth muscle actin messenger RNA
      and protein expression in growing and quiescent cultured human and rat
      subcutaneous tissue fibroblasts. These data confirm that in vitro the behavior of
      the three different transforming growth factor-beta isoforms is similar, whereas
      in vivo transforming growth factor-beta isoforms possibly play different but
      complementary roles in myofibroblast modulation during wound repair.

PMID- 17177826
TI  - Differential expression of platelet-derived growth factor receptors in porcine
      fibroblasts cultured from skin and granulation tissue.
AB  - This study investigated the biological response of fibroblasts cultured from
      uninjured skin and granulation tissue from different stages of healing wounds to
      the three isoforms of platelet-derived growth factor. Fibroblasts were derived by
      explant culture from the skin or the granulation tissue that formed within open
      mesh nylon Schilling-Hunt chambers (postoperative days 10, 20, 30, and 50) which
      had been implanted subcutaneously in the backs of domestic pigs. Cells were
      cultured under identical conditions in Dulbecco's modified Eagle's medium
      containing 10% fetal calf serum. Mitogenic activity was measured with (3)H
      thymidine incorporation into DNA. Fibroblasts from normal skin responded equally
      well to all of the platelet-derived growth factor isoforms in the mitogenic
      assays. All of the wound fibroblasts exhibited a decreased response to platelet
      derived growth factor compared with those from skin. Granulation tissue
      fibroblasts responded to platelet-derived growth factor BB, less to platelet
      derived growth factor AB, and poorly to platelet-derived growth factor AA. These
      results correlated with a significantly decreased growth rate of fibroblasts in
      culture from both 30- and 50-day postsurgical wound tissue compared with normal
      skin. Western blot studies of cell membrane extracts showed that wound
      fibroblasts contained less than 20% as many platelet-derived growth factor-alpha
      receptors as found in fibroblasts cultured from normal skin. No significant
      difference in the amount of platelet-derived growth factor-beta receptor was
      detected. The decreases in platelet-derived growth factor-alpha receptors are
      sufficient to account for the diminished response of the wound fibroblasts to all
      platelet-derived growth factor isoforms and the differential loss of
      responsiveness to platelet-derived growth factor AA. These results show that
      fibroblasts derived from granulation tissue of pig skin wounds exhibit a
      decreased growth response to platelet-derived growth factor and a decreased
      growth rate in culture media as compared with fibroblasts derived from uninjured
      skin. How these differences may relate to the physiologic characteristics of
      normal and healing-impaired wounds is considered.

PMID- 17177827
TI  - Acidic fibroblast growth factor reduces renal morphologic and functional
      indicators of injury caused by ischemia and reperfusion.
AB  - Therapeutic effects of acidic fibroblast growth factor on postischemic renal
      injury were evaluated in a rat model of bilateral renal ischemia (60 minutes) and
      reperfusion (7 days). Twenty-four rats were randomly divided into two groups (12
      rats each). After 60 minutes of ischemia and at the onset of reperfusion, rats in
      the acidic fibroblast growth factor-treated group received 2.6 microg of acidic
      fibroblast growth factor/rat in 50 microl of phosphate-buffered saline solution
      containing 0.1% heparin (w/v) through the jugular vein, whereas the rats in the
      phosphate-buffered saline solution-treated group received the same vehicle
      without acidic fibroblast growth factor. Compared with the phosphate-buffered
      saline solution-treated group, rats in the acidic fibroblast growth factor
      treated group had significantly lower blood urea nitrogen (83.13 +/- 26.07 versus
      176.36 +/- 62.36, p < 0.05) and serum creatinine (0.73 +/- 0.14 versus 1.14 +/-
      0.36, p < 0.05) levels 1 day after occlusion. Histopathologic scores showed much
      less renal damage on day 1 in the acidic fibroblast growth factor-treated rats
      compared with the phosphate-buffered saline solution controls. We conclude that
      intravenous administration of acidic fibroblast growth factor offers significant
      protection against postischemic renal injury and these protective effects may
      come from its nonmitogenic effects such as the regulation of vessel tone and
      calcium concentration in the body.

PMID- 17177829
TI  - De novo expression of MECA-79 glycoprotein-determinant on developing B
      lymphocytes in gut-associated lymphoid tissues.
AB  - Rabbit is one of several species that depend on development of B lymphocytes in
      gut-associated lymphoid tissues for primary immunoglobulin-repertoire
      diversification. The rabbit appendix is an important site of early B-lymphocyte
      development. We previously reported that peripheral lymph node addressin detected
      by monoclonal antibody (mAb) MECA-79 played a role in recruitment of immature
      blood-borne B cells into neonatal rabbit appendix. Here, we report expression of
      an approximately 127 000 MW O-linked sulphated proteoglycan on developing B cells
      in appendix and Peyer's patches recognized by the mAb MECA-79. Binding of the mAb
      to B lymphocytes was sensitive to enzyme treatment with O-sialoglycoprotease and
      expression was partially inhibited by sodium chlorate, a metabolic inhibitor of
      sulphation. The proportions of MECA-79(+) B lymphocytes gradually increased from
      < 0.5% at 3 days to > 70% at 6 weeks in appendix and Peyer's patches. The
      proportions of MECA-79(+) B lymphocytes in spleen and peripheral blood were very
      low (0.5-2%). However, the MECA-79 determinant was detected on B cells in splenic
      germinal centres after immunization. In situ labelling of appendix cells showed
      that the MECA-79 determinant was expressed on fluorescein-labelled B lymphocytes
      that migrated from appendix into mesenteric lymph nodes. B-cell MECA-79 may be
      involved in interactions with T cells and/or dendritic cells. Alternatively,
      because we found that lymphatic endothelium in the thymus-dependent area of
      appendix, a site for lymphocyte exit, expressed P-selectin (CD62P), interaction
      of the MECA-79 determinant on B cells with CD62P may have a role in the exit of B
      lymphocytes from rabbit appendix.

PMID- 17177830
TI  - Glucocorticoid-induced tumour necrosis factor receptor family-related receptor
      signalling exacerbates hapten-induced colitis by CD4+ T cells.
AB  - The glucocorticoid-induced tumour necrosis factor receptor family related gene
      (GITR) has been reported to be expressed on the activated T and CD4(+)CD25(+)
      regulatory T cells (Treg). Signalling triggered by GITR not only neutralizes the
      suppressive effect of Treg cells, but also augments activation, proliferation and
      cytokine production of effector T cells. To test the role of GITR in 2,4,6
      trinitrobenzene sulphonic acid (TNBS)-induced colitis - a murine model of mucosal
      inflammation - TNBS-injected Balb/c mice were treated with agonistic anti-GITR
      monoclonal antibody (mAb). Anti-GITR treatment increased the death rate compared
      to rat IgG-treated mice. Typically, death occurred within 4 days after the TNBS
      injection when the mice were treated with anti-GITR. The mice that survived anti
      GITR treatment suffered from severe inflammation in their entire intestines.
      CD4(+) T-depletion protected the mice from colitis; even an anti-GITR effect was
      not apparent. In contrast, CD8(+) T depletion showed less protective than did
      CD4(+) T depletion. Stimulation of GITR enhanced the production of
      proinflammatory cytokines including interferon (IFN)-gamma, tumour necrosis
      factor (TNF)-alpha, interleukin (IL)-6 and IL-12. It also enhanced the humoral
      response such as serum levels of IgG(2b) and IgA, which was completely dependent
      on CD4(+) T cells. Taken together, this study demonstrated that GITR signalling
      on CD4(+) T cells is involved in the development and progress of colitis by
      enhancing both T helper type 1 (Th1) and Th2 type responses.

PMID- 17177831
TI  - The strength of the chemotactic response to a CCR5 binding chemokine is
      determined by the level of cell surface CCR5 density.
AB  - We have shown that the intensity of expression of the C-C chemokine receptor CCR5
      at the single CD4(+) cell level strongly determines the efficiency of its
      function as a coreceptor for human immunodeficiency virus type 1. By analogy, we
      examined if the number of CCR5 molecules at the cell surface might determine its
      chemotactic response to CCR5 ligands. To test this hypothesis, we measured by
      flow cytometry the migration of primary human T cells towards the CCR5-binding
      chemokine CCL5 in vitro. First, we observed a dose-dependent blockage of this
      migration exerted by an anti-CCR5 monoclonal antibody. Second, we sorted
      peripheral blood mononuclear cells into five subpopulations expressing various
      cell surface CCR5 densities, and observed a correlation between the intensity of
      migration towards CCL5 and the level of CCR5 expression on these subpopulations.
      Third, we transduced CCR5(+) peripheral blood mononuclear cells with the CCR5
      gene, and observed that the CCR5 over-expression induced an over-migration
      towards CCL5. Finally, we observed in healthy donors a correlation between the
      chemotactic response of peripheral blood CD8(+) T cell to CCL5 and their level of
      surface CCR5 expression. T-cell surface CCR5 density, which is constant over time
      for a given individual, but varies drastically among individuals, might therefore
      be an important personal determinant of T-cell migration in many biological
      situations where CCR5-binding chemokines play a role, such as graft rejection, T
      helper 1-mediated auto-immune diseases, and infectious diseases involving CCR5.
      Moreover, our data highlight the therapeutic potential of CCR5 antagonists in
      these situations.

PMID- 17177832
TI  - Hematologic changes after splenectomy for cytoreduction: implications for
      predicting infection and effects on chemotherapy.
AB  - Postsplenectomy leukocytosis and thrombocytosis are common findings in trauma
      patients. The intent of this study is to describe postsplenectomy hematologic
      changes in gynecological oncology surgery and subsequent chemotherapy. We
      performed a retrospective record review of gynecological oncology patients at our
      institutions. Postsurgical hematologic changes, infectious morbidity, and pre-
      and post-chemotherapy hematologic changes were noted. Data were analyzed using
      repeated measures analysis of variance. We identified 27 patients who underwent
      cytoreductive surgery with splenectomy. Thirteen patients with splenectomy had
      postoperative chemotherapy data available, and we matched these patients with 13
      control patients who underwent cytoreduction surgery without splenectomy and
      postoperative chemotherapy. Nine of the 27 splenectomy patients had documented
      infectious morbidity. There was a significant difference in postoperative
      platelet counts between the infected and the noninfected splenectomy patients (P=
      0.037), and a significant difference between splenectomy and control patients for
      white blood cell (WBC) counts (P = 0.007). Patients with splenectomy had higher
      precycle WBC, absolute neutrophil count (ANC), platelet counts, and higher
      postcycle nadir levels in all cycles compared to control patients. There was a
      significant overall difference between splenectomy patients and controls with
      regard to WBC (P = 0.001), ANC (P = 0.005), and platelet counts (P = 0.016)
      during chemotherapy cycles. Median postchemotherapy nadir WBC was 4.4 (range: 3.4
      4.8) for the splenectomy group versus 2.8 (range: 2.5-3.0) for the control group.
      Median postchemotherapy nadir ANC was 1800 (range: 1320-2450) for the splenectomy
      group and 1001 (range: 864-1064) for the control group. Median postchemotherapy
      nadir platelet count was 222 (range: 181-277) for the splenectomy patients and
      169 (range 164-215) for the control patients. In conclusion, the patients who
      undergo splenectomy as part of cytoreductive surgeries have a statistically
      significant leukocytosis and insignificant thrombocytosis relative to the control
      patients. Leukocytosis alone is not an accurate indicator of infection.
      Splenectomy is not associated with an increased risk of chemotherapy-related
      neutropenia and thrombocytopenia.

PMID- 17177834
TI  - Insulin-like growth factor, insulin-like growth factor-binding protein-4, and
      pregnancy-associated plasma protein-A gene expression in human granulosa cell
      tumors.
AB  - The insulin-like growth factor (IGF) system plays an important role in
      folliculogenesis. It is also thought to contribute to the pathogenesis of many
      cancers, including those of the ovarian epithelium. In the human follicle, the
      predominant IGF is IGF-II and its actions are modulated by insulin-like growth
      factor-binding protein-4 (IGFBP-4), the IGFBP-4 protease, and the pregnancy
      associated plasma protein-A (PAPP-A). These peptide components are synthesized by
      the granulosa cells of the developing follicle. The aim of this study was to
      characterize the expression of these components of the IGF system in granulosa
      cell tumors (GCT) of the ovary. IGF-I, IGF-II, IGFBP-4, and PAPP-A gene
      expression was determined in a panel of GCT and compared to the levels in normal
      ovary and in epithelial ovarian tumors. Although both the IGF-I and IGF-II genes
      were expressed in the GCT, the levels were lower than in the other tissue groups.
      IGFBP-4 expression was also low in the GCT, whereas PAPP-A gene expression was
      highest in the GCT. These findings were unexpected given the prominent role this
      signaling system plays in normal granulosa cells. In conclusion, these
      observations suggest that the IGF system may have a limited role in the
      pathogenesis of GCT with PAPP-A subserving a function other than IGFBP-4
      proteolysis.

PMID- 17177833
TI  - Expression profile of ovarian tumors: distinct signature of Sertoli-Leydig cell
      tumor.
AB  - Epithelial ovarian tumors are the most common subtype of ovarian cancer. In this
      study, we reveal distinct expression signatures of previously uncharacterized
      ovarian carcinoma subtypes, including endometrioid component of mixed ovarian
      tumor and Sertoli-Leydig tumor. Both subtypes were compared to the most common
      and well-characterized ovarian epithelial carcinoma of the serous type. These
      comparisons were performed by complementaryDNA (cDNA) microarrays allowing high
      fidelity measurements of the expression levels of 39,360 human individual cDNA
      species representing both known and unknown human genes. Functional analysis of
      differentially expressed genes in Sertoli-Leydig tumor revealed an upregulation
      in sonic hedgehog pathway, deregulation of several metabolic pathways especially
      in amino acid metabolism and overexpression of genes associated with protein
      synthesis, including ribosomal genes.

PMID- 17177835
TI  - Increased risk for abnormalities on perioperative colon screening in patients
      with microsatellite instability-positive endometrial carcinoma.
AB  - Microsatellite instability (MSI) is a feature of certain hereditary and sporadic
      endometrial and colon cancers. We set out to determine whether molecular
      stratification of endometrial cancers based on tumor MSI status could help
      identify patients at increased risk for abnormalities found on perioperative
      colon screening. From a prospectively accrued series of 413 patients, medical
      records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients
      with MSI negative (MSI-) endometrial cancers, matched by year of diagnosis. We
      reviewed clinicopathologic data and results of perioperative colon screening.
      Differences were analyzed using Fisher exact test and logistic regression
      analysis. There were no significant clinicopathologic differences between the two
      cohorts. Sixty-five percent of patients in each group underwent perioperative
      colon screening. However, patients with MSI+ cancers had a twofold increase in
      the frequency of colonic abnormalities (30% versus 14.8%, P = 0.044) over those
      with MSI- cancers. Furthermore, the only primary colon cancers (N = 2) were found
      in women with MSI+ endometrial cancers that were unmethylated at the MLH1
      promoter. Our data suggest that patients with MSI+ endometrial cancers are at
      increased risk for abnormalities on perioperative colon screening. Those with
      MSI+MLH1 unmethylated cancers appear to be at highest risk.

PMID- 17177836
TI  - Telomerase antisense inhibition for the proliferation of endometrial cancer in
      vitro and in vivo.
AB  - The objective of this study was to investigate the antitumor effect of antisense
      telomerase oligodeoxynucleotides to endometrial cancer cells in vitro and in
      vivo. Antisense oligodeoxynucleotides (ODNs) against the human telomerase
      transcripatse (hTERT) synthesized to serve as telomerase inhibitors. Reverse
      transcription-polymerase chain reaction and 3-[4,5-dimethylthiazol-2yl]-2,5
      diphenyltetrazolium bromide (MTT) assay were used to test the expression of hTERT
      messengerRNA (mRNA) and inhibition of cell proliferation in vitro. In vivo,
      antitumor effects of ODNs or combined with cisplatin were evaluated in
      endometrial cancer xenograft. Telomerase activity was tested by telomeric repeat
      amplification protocol. Antisense ODNs could inhibit proliferation of human
      endometrial cancer cells (HEC-1-A) in vitro, and downregulate the expression
      hTRET mRNA in a dose- and period-dependent manner. The tumor growth inhibitory
      rate of low- and high-dose ODNs were 34.20% and 89.21%, and combined group was
      75.30%. Telomerase activity was downregulated to 87.32% compared to the control
      in the ODNs-treated xenograft tumors. Antisense oligonucleotides of hTERT
      effectively inhibit the growth of endometrial cancer cell line. Telomerase
      inhibitor might be a new strategy for chemotherapy or chemoprevention in
      endometrial cancer.

PMID- 17177837
TI  - Role of [18F]fluoro-2-deoxy-D-glucose positron emission tomography in re
      recurrent cervical cancer.
AB  - Cervical cancer patients with histologically documented re-recurrence after
      curative salvage therapy or unexplained tumor marker elevation (negative computed
      tomography and/or magnetic resonance imaging [CT-MRI]) proven to be a re
      recurrence when a further attempt for cure (or control of cancer) appeared
      feasible were enrolled. Lesion status was determined from pathology or clinical
      follow-up for at least 12 months. Management decisions were recorded with CT-MRI
      alone and incorporating [18F]fluoro-2-deoxy-D-glucose positron emission
      tomography (FDG-PET), respectively. The benefits calculated were based on
      clinical impact because of the FDG-PET findings. Cox proportional hazards model
      was used to select independent prognostic covariates. Of the 26 patients who were
      eligible for analysis, 12 (46.2%) patients had positive impacts due to PET.
      Squamous cell carcinoma (SCC, P = 0.029), re-recurrence at distant metastasis
      only (P = 0.012), and level of SCC antigen < or = 4 ng/mL (P = 0.005) were
      significantly associated with better survival. A scoring system using these
      covariates defined three distinct prognostic groups (P = 0.0001). Patients with
      score 0 had a 36-month cumulative survival rate of 80%. Using this prognostic
      scoring system, FDG-PET may facilitate selecting appropriate management for the
      individual patient with re-recurrent cervical cancer.

PMID- 17177838
TI  - Analysis of p53 codon 72 polymorphism and its association with human
      papillomavirus 16 and 18 E6 in Chinese cervical lesions.
AB  - The aim of this study was to analysis the relationship between p53 codon 72
      polymorphism with human papillomavirus (HPV) 16 and 18 E6 in Chinese cervical
      cancer. A total of 81 cervical squamous cancer (specimens of G1, G2, and G3 are
      13, 24, and 44, respectively; and of stage IB, IIA, IIB, and IIIA are 15, 37, 24,
      and 5, respectively), 18 cervical adenocarcinoma, 88 cervical intraepithelial
      neoplasm (CIN) (specimens of CIN II and III are 30 and 58), and 60 normal
      cervical specimens were included in this study. Polymerase chain reaction was
      used to examine p53 genotypes and HPV 16 and 18 E6. The frequencies of p53 Arg
      homozygosity in cervical squamous cancer, cervical adenocarcinoma, and CIN (II
      III) were 58.02%, 55.55%, and 59.09%, respectively, that was much higher than
      that of p53 Arg/Pro heterozygosity (30.86%, 27.78%, and 21.59%) and of p53 Pro
      homozygosity (11.12%, 16.67%, and 19.32%) in each groups and higher than the
      frequency of p53 Arg homozygosity in normal samples (23.33%). There is no
      statistic difference in the normal samples for the frequency of p53 Arg
      homozygosity, p53 Arg/Pro heterozygosity, and p53 Pro homozygosity (23.33%,
      40.00%, and 36.67%, respectively). The frequency of p53 Arg homozygosity in high
      risk (HR)-HPV E6-positive cervical squamous cancer samples (64.06%) is much
      higher than that in (HR)-HPV E6-negative cervical squamous cancer samples
      (35.29%) and in HR-HPV E6-positive normal samples (33.33%). No difference of p53
      codon 72 polymorphism was found according to FIGO staging and grades. In
      conclusion, based on the findings of this study, it is suggested that p53 Arg
      homozygosity could act as a potential risk factor for the tumorigenesis of the
      cervix. p53 codon 72 polymorphism has no relation with the FIGO staging and
      grades of cervical cancer. p53 Arg homozygosity and HR-HPV E6 positive
      simultaneously can predict the fate of cervical lesions.

PMID- 17177839
TI  - The expression of epidermal growth factor receptor, vascular endothelial growth
      factor, matrix metalloproteinase-2, and cyclooxygenase-2 in relation to human
      papilloma viral load and persistence of human papillomavirus after conization
      with negative margins.
AB  - The aim of this study was to investigate the correlations between human
      papillomavirus (HPV) load and vascular endothelial growth factor (VEGF),
      epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP-2), and
      cyclooxygenase-2 (COX-2), and to identify biomarkers that may predict high-risk
      HPV clearance or persistence after conization with negative margins. The
      following samples were analyzed: 77 paraffin-embedded specimens from patients
      with cervical intraepithelial neoplasia (CIN), including 27 CIN 2 conization
      specimens and 50 CIN 3 conization specimens. Immunohistochemical analysis was
      performed with antibodies to VEGF, EGFR, MMP-2, and COX-2. Hybrid capture II
      testing was used to detect HPV DNA. VEGF expression was significantly associated
      with HPV load (rho = 0.27186, P = 0.0191), while COX-2 expression was
      significantly and inversely associated with HPV load (rho = -0.34309, P =
      0.0028). In univariate analysis, HPV load (P = 0.0112) and VEGF expression (P =
      0.0274) were significantly associated with high-risk HPV clearance or persistence
      after conization with negative margins. In multiple regression analysis, high
      viral load (relative light unit/positive control > 500) and positive VEGF
      expression were significantly associated with high-risk HPV persistence after
      conization with negative margins (odds ratio [OR]: 9.915, CI: 1.891-51.994; OR:
      6.661, CI: 1.208-36.722, respectively). In conclusion, VEGF expression is related
      to HPV load, while COX-2 expression is inversely related to HPV load, and
      immunohistochemical analysis of VEGF expression and HPV viral load are a
      significant and an independent prognostic indicator of high-risk HPV persistence
      after conization with negative margins.

PMID- 17177840
TI  - Increased expression of galectin-1 during the progression of cervical neoplasia.
AB  - Galectin-1, a member of the beta-galactoside-binding family, is widely expressed
      in epithelial and immune cells. It is involved in several normal and pathologic
      processes, such as cancer progression, metastasis, and immunobiology. Galectin-1
      was found to be overexpressed in various cancer cells and the corresponding
      benign tissue. Therefore, it has been described as a marker for tumor progression
      in some malignancies. In the current study, the expression of galectin-1 was
      examined in 80 formalin-fixed, paraffin-embedded cervical tissues: 20 benign
      cervical specimen, 20 low-grade squamous intraepithelial lesions (LGSIL), 20 high
      grade squamous intraepithelial lesions (HGSIL), and 20 invasive squamous cell
      carcinomas (ISCC). Immunohistochemical analyses showed that the intensity of the
      galectin-1 expression on stromal cells next to the transformed cells increased
      according to the pathologic grade: benign cervical tissue < LGSIL < HGSIL < ISCC
      (P < 0.001). The epithelial cells were always negative for galectin-1. These
      results suggest that galectin-1 expression on stromal cells increases with the
      histopathologic grade of cervical tissues, and it can be concluded that this
      increase is associated with the progression of cervical neoplasia.

PMID- 17177841
TI  - Antiproliferative and antiviral mechanisms of ursolic acid and dexamethasone in
      cervical carcinoma cell lines.
AB  - The chemical structure of ursolic acid is very similar to that of dexamethasone,
      a synthetic glucocorticoid. Herein, we investigated the antiproliferative and
      antiviral effects of ursolic acid and dexamethasone in human papillomavirus (HPV)
      associated cervical cancer cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazonium bromide assay to measure antiproliferative activity, and also
      characterized apoptosis by DNA fragmentation, 4'-6-diamidino-2-phenylindole
      (DAPI) staining, and flow cytometry (FACS) analysis. We investigated apoptosis
      related proteins using western blots. After in vitro treatment, we used reverse
      transcription-polymerase chain reaction for the expression of the HPV E6/E7 gene
      to observe the antiviral effects. Ursolic acid suppressed the growth of HPV
      positive cervical carcinoma cells (HeLa, CaSki, and SiHa) in a dose- and time
      dependent manner, but not the HPV-negative cervical cancer cell line (C33A).
      Ursolic acid-treated HeLa cells showed typical apoptosis characteristics in DNA
      fragmentation, DAPI staining, and FACS analysis. The expression of Fas protein
      was induced, and caspase-8, caspase-3, and poly ADP-ribose polymerase (PARP)
      proteins were cleaved after ursolic acid treatment. HPV-18 E6/E7 gene expression
      decreased after ursolic acid treatment in HeLa cells, but the levels of p53 and
      Rb proteins did not change. In contrast, dexamethasone, which has a similar
      structure, did not inhibit proliferation. Our findings may offer new insight into
      the mechanism of antiproliferative and antiviral effect of ursolic acid. Also,
      these results suggest that ursolic acid might be a useful anticancer drug in
      treatment of HPV-associated cervical neoplasia.

PMID- 17177842
TI  - Comparing normal primary endocervical adenoepithelial cells to uninfected and
      influenza B virus infected human cervical adenocarcinoma HeLa cells.
AB  - Human adenocarcinoma HeLa cells surviving infection with low (10(-9) units),
      medium (10(-6) units), and high (10(-2) units) influenza B titers were compared
      to their uninfected precursors and to normal endocervical adenoepithelial and
      metaplastic cells using Papanikolaou-staining method and immunocytochemistry.
      Normal primary endocervical and infected HeLa cells surviving infection shared
      similar morphologic, phenotypic, and divisional patterns that differed
      drastically from those of uninfected HeLa cells. The number of infected hosts
      surviving 6-7 days of viral exposure did not change during 3-week follow-up
      period, and their cyclin E levels suggested that they had been arrested to the G1
      phase of the cell cycle by viral stress. Our findings suggest that in addition to
      apoptosis, nononcogenic viral stress activated the expression of endocervical
      metaplastic-like motifs in surviving hosts. A mechanism of cell response to
      nononcogenic viral stress was proposed to explain these findings. We conclude
      that nononcogenic respiratory viruses specifically target and eliminate abnormal
      cells ectopically overexpressing appropriate receptors and may complement current
      treatments of cervical cancer.

PMID- 17177843
TI  - Giant ovarian cysts: is a pre- and intraoperative drainage an advisable
      procedure?
AB  - There has been a considerable debate over the merits of a pre- or intraoperative
      drainage of giant ovarian cysts, which represented a very frequent approach
      before definitive surgery in the past. Including our presented case of a 57-year
      old woman with a 49 kg mucinous cystadenoma, 19 patients with giant ovarian cysts
      weighing more than 40 kg were reported in the literature since 1970. An incidence
      of 37% of malignant and low malignant potential tumors was found. Based on a
      critical evaluation of the medical courses and the discussed miscellaneous
      advantages and complications, we conclude that a pre- and intraoperative drainage
      should be avoided.

PMID- 17177844
TI  - A rare case of choroidal metastasis presented after conservative management of
      endometrial cancer.
AB  - Hematogenous dissemination from endometrial cancer is quite rare. We report a 31
      year-old woman who developed choroidal metastasis following conservative
      management of early-stage endometrial carcinoma. She had received kidney
      transplantation and was taking steroids and cyclosporine. Three years after
      hysterectomy for persistent endometrial carcinoma, she developed multiple
      metastatic disease (to both lungs and right pelvis), and while on treatment with
      paclitaxel and carboplatin, she complained of a rapid visual deterioration.
      Ophthalmologic evaluation revealed a metastatic choroidal tumor associated with
      multiple central nervous system metastases. The patient refused further treatment
      and died 1 month after diagnosis of choroidal involvement. In conclusion, this is
      the first reported case of choroidal metastasis from endometrial cancer and
      highlights the need to consider immunosuppressive treatment as an absolute
      contraindication to conservative fertility-sparing treatment in gynecological
      malignancies.

PMID- 17177845
TI  - The multiple roles of Id-1 in cancer progression.
AB  - Id-1 (Inhibitor of differentiation/DNA binding) is a member of the helix-loop
      helix protein family expressed in actively proliferating cells. It regulates gene
      transcription by heterodimerization with the basic helix-loop-helix transcription
      factors and therefore inhibits them from DNA binding and transactivation of their
      target genes. Early studies showed that Id-1 functions mainly as a regulator in
      cellular differentiation of the muscle cells. The oncogenic role of Id-1 was
      revealed recently by the finding that Id-1 expression was able to induce cancer
      cell growth and promote cell survival. In addition, Id-1 protein was frequently
      overexpressed in over 20 types of cancer, supporting its role in the
      tumorigenesis of a wide range of tissues. However, the fact that Id-1 was able to
      activate multiple pathways involved in tumor progression suggests that Id-1 may
      in addition function in promotion of tumor development. For example,
      overexpression of Id-1 was found to induce expression of MT1-MMP protein, leading
      to invasion of breast cancer cells. A close association between Id-1 expression
      and angiogenesis has also been demonstrated recently in both normal and cancer
      cells. Accordingly, in prostate cancer cells, expression of Id-1 was able to
      activate EGF-R and nuclear factor-kappaB activities and resulted in progression
      to androgen independence. In addition, in both nasopharyngeal carcinoma and
      prostate cancer cells, Id-1 expression was found to protect the cells from
      chemotherapeutic drug-induced apoptosis through regulation of the Raf-1/MAPK and
      JNK pathways. This review will discuss recent evidence supporting the role of Id
      1 in tumor progression and the mechanisms involved.

PMID- 17177846
TI  - 5-FdUrd-araC heterodinucleoside re-establishes sensitivity in 5-FdUrd- and AraC
      resistant MCF-7 breast cancer cells overexpressing ErbB2.
AB  - ErbB2 overexpressing breast tumors have a poor prognosis and a high risk to
      develop chemoresistance to therapeutic treatment. "Chemoresistance" is a response
      of cells to toxic stress, and, although it is a common phenomenon, it is still
      poorly defined. However, a detailed understanding is required to target
      desensitized pathways and mechanisms for successful reactivation as part of a
      tailored therapy. To gain insight, which malfunctions contribute to
      chemoresistance, two mechanisms relevant for tissue homeostasis, the regulation
      of the cell cycle and of apoptosis, were investigated. Maternal MCF-7- and ErbB2
      overexpressing MCF-7(erbB2) breast cancer cells were long term pretreated with 2'
      deoxy-5-fluorodeoxyuridine (5-FdUrd) or 1-beta-d-arabinofuranosylcytosine (AraC)
      and the acquisition of drug-insensitivity was analyzed. A phosphate-conjugated
      heterodinucleoside consisting of one 5-FdUrd- and one AraC-moiety (5-fluoro-2'
      desoxyuridylyl-(3'-->5')-Arabinocytidine) was utilized as a tool to assess the
      type of acquired resistances. ErbB2-overexpression disrupted proper cell cycle
      regulation and furthermore facilitated the development of an apoptosis-refractory
      phenotype upon exposure to 5-FdUrd. Experiments with dimer 5-FdUrd-araC in ErbB2
      overexpressing MCF-7(erbB2) cells, and also with nucleoside 5-FdUrd in maternal
      MCF-7 cells, evidenced that the phenotypes of resistance to cell cycle inhibition
      and to apoptosis induction were differently affected. The expression profile of
      cyclin D1 (but not that of p53, p21, or p27) correlated with the proliferative
      phenotypes and nuclear accumulation of apoptosis inducing factor (but not
      activation of caspase 7) with apoptotic phenotypes. Dimer 5-FdUrd-araC overrode
      acquired chemoresistances, whereas combined application of 5-FdUrd and AraC
      exhibited significantly less activity. Dimer 5-FdUrd-araC remained active in MCF
      7 clones most likely by circumventing the prerequisite of first-step
      phosphorylation. The acquisition of chemoresistance encompassed the affection of
      apoptosis- and cell-cycle regulation to, respectively, different extents. Thus,
      drug-induced cell cycle arrest and apoptosis induction are independent of each
      other.

PMID- 17177847
TI  - Differential expression of glucose transporter isoforms during embryonic stem
      cell differentiation.
AB  - In mouse blastocysts six facilitative glucose transporter isoforms (GLUT)1-4, 8
      and 9 are expressed. We have used the mouse embryonic stem (ES) cell line D3 and
      spontaneously differentiating embryoid bodies (EB) to investigate GLUT expression
      and the influence of glucose during differentiation of early embryonic cells.
      Both ES cells and EBs (2d-20d) expressed GLUT1, 3, and 8, whereas the isoforms 2
      and 4 were detectable exclusively in EBs. Differentiation-associated expression
      of GLUT was analyzed by double staining with stage-specific embryonic antigen
      (SSEA-1), cytokeratins (CK18, 19), nestin, and desmin. Similar to trophoblast
      cells in mouse blastocysts the outer cell layer of endoderm-like cells showed a
      high GLUT3 expression in early EBs. In 20-day-old EBs no GLUT3 protein and only
      minor GLUT3 mRNA amounts could be detected. A minimal glucose concentration of 5
      mM applied during 2 and 8 days of EB culture resulted in up-regulated GLUT4, Oct
      4 and SSEA-1 levels and a delay in EB differentiation. We conclude that GLUT
      expression depends on cellular differentiation and that the expression is
      modulated by glucose concentration. The developmental and glucose-dependent
      regulation of GLUT strongly suggests a functional role of glucose and glucose
      transporters in ES cell differentiation and embryonic development.

PMID- 17177848
TI  - Neuron-like differentiation of adipose tissue-derived stromal cells and vascular
      smooth muscle cells.
AB  - Adipose tissue-derived stromal cells (ADSC) have previously been shown to possess
      stem cell properties such as transdifferentiation and self-renewal. Because
      future clinical applications are likely to use these adult stem cells in an
      autologous fashion, we wished to establish and characterize rat ADSC for pre
      clinical tests. In the present study, we showed that rat ADSC expressed stem cell
      markers CD34 and STRO-1 at passage 1 but only STRO-1 at passage 3. These cells
      could also be induced to differentiate into adipocytes, smooth muscle cells, and
      neuron-like cells, the latter of which expressed neuronal markers S100, nestin,
      and NF70. Isobutylmethylxanthine (IBMX), indomethacin (INDO), and insulin were
      the active ingredients in a previously established neural induction medium (NIM);
      however, here we showed that IBMX alone was as effective as NIM in the induction
      of morphological changes as well as neuronal marker expression. Finally, we
      showed that vascular smooth muscle cells could also be induced by either NIM or
      IBMX to differentiate into neuron-like cells that expressed NF70.

PMID- 17177849
TI  - Investigating the effects of preinduction on human adipose-derived precursor
      cells in an athymic rat model.
AB  - The osteogenic potential of human adipose-derived precursor cells seeded on
      medical-grade polycaprolactone-tricalcium phosphate scaffolds was investigated in
      this in vivo study. Three study groups were investigated: (1) induced--stimulated
      with osteogenic factors only after seeding into scaffold; (2) preinduced--induced
      for 2 weeks before seeding into scaffolds; and (3) uninduced--cells without any
      introduced induction. For all groups, scaffolds were implanted subcutaneously
      into the dorsum of athymic rats. The scaffold/cell constructs were harvested at
      the end of 6 or 12 weeks and analyzed for osteogenesis. Gross morphological
      examination using scanning electron microscopy indicated good integration of host
      tissue with scaffold/cell constructs and extensive tissue infiltration into the
      scaffold interior. Alizarin Red histology and immunostaining showed a heightened
      level of mineralization and an increase in osteonectin, osteopontin, and collagen
      type I protein expression in both the induced and preinduced groups compared with
      the uninduced groups. However, no significant differences were observed in these
      indicators when compared between the induced and preinduced groups.

PMID- 17177850
TI  - Cell surface antigens on rat neural progenitors and characterization of the CD3
      (+)/CD3 (-) cell populations.
AB  - While the hematopoietic lineage has been extensively studied using cluster of
      differentiation (CD) antibodies, very few data are available on the extracellular
      epitopes expressed by rat neural progenitors (rNPC) and their derivatives. In the
      present study, we used flow cytometry to screen 47 cell surface antigens,
      initially known as immune markers. The quantitative analyses were performed on
      rat neurospheres and compared with primary cultures of astroglial cells or
      cerebellar neurons. Several antigens such as CD80 or CD86 were clearly
      undetectable while others, like CD26 or CD161, showed a weak expression.
      Interestingly, 10% and 15% of the cells were immunopositive for CD172a and CD200,
      two immunoglobulin superfamily members preferentially expressed by glial or
      neuronal cells, respectively. Over 40% of the cells were immunopositive for CD3,
      CD71, or MHCI. The biological significance of the latter markers in rNPC remains
      to be determined but analyses of the CD3(-)/CD3(+) populations isolated by
      magnetic cell separation revealed differences in their cell fate. Indeed, CD3(+)
      cells did not establish neurospheres and differentiated mostly into GFAP(+) cells
      while CD3(-) cells were able to generate neurospheres upon mitogen treatment and
      gave rise to GFAP(+), A2B5(+), Tuj-1(+), and RIP(+) cells under differentiating
      conditions. In contrast, CD71(-)/CD71(+) cells did not show any significant
      difference in their proliferating and differentiating potentials. Finally, it is
      worth noting that an subpopulation of cells in rat neurospheres exhibit an
      immunoreactivity against anti-CD25 (IL2 receptor) and anti-CD62L (L-selectin)
      antibodies. The results reveal particular surface antigen profiles, giving new
      perspectives on the properties of rat brain-derived cells.

PMID- 17177851
TI  - Down-regulation of Sox10 with specific small interfering RNA promotes
      transdifferentiation of Schwannoma cells into myofibroblasts.
AB  - Neural crest-derived cells are noted for the long lasting plasticity during
      lineage commitment process and the potential for transdifferentiation into other
      neural crest derivatives. Schwann cells in particular have been reported to
      transdifferentiate into melanocytes and myofibroblasts. Detailed studies of
      transdifferentiation at the molecular level have been hampered by difficulty in
      isolating sufficient quantity of primary cells or cellular materials. Here, we
      describe a robust in vitro system in which Schwannoma cells undergo an apparent
      transdifferentiation into myofibroblasts. Importantly, we induce the
      transdifferentiation by down-regulating a single transcription factor, Sox10,
      thereby identifying a key molecular event in this process. Myofibroblasts thus
      generated showed carbachol-stimulated contraction and calcium transients and
      express several established myofibroblast-specific genes. These results suggest
      that generating desired cell types based on "knock-down" of critical genes may be
      a viable strategy.

PMID- 17177853
TI  - Interactive properties of human glioblastoma cells with brain neurons in culture
      and neuronal modulation of glial laminin organization.
AB  - The harmonious development of the central nervous system depends on the
      interactions of the neuronal and glial cells. Extracellular matrix elements play
      important roles in these interactions, especially laminin produced by astrocytes,
      which has been shown to be a good substrate for neuron growth and axonal
      guidance. Glioblastomas are the most common subtypes of primary brain tumors and
      may be astrocytes in origin. As normal laminin-producing glial cells are the
      preferential substrate for neurons, and glial tumors have been shown to produce
      laminin, we questioned whether glioblastoma retained the same normal glial-neuron
      interactive properties with respect to neuronal growth and differentiation. Then,
      rat neurons were co-cultured onto rat normal astrocytes or onto three human
      glioblastoma cell lines obtained from neurosurgery. The co-culture confirmed that
      human glioblastoma cells as well as astrocytes maintained the ability to support
      neuritogenesis, but non-neural normal or tumoral cells failed to do so. However,
      glioblastoma cells did not distinguish embryonic from post-natal neurons in
      relation to neurite pattern in the co-cultures, as normal astrocytes did.
      Further, the laminin organization on both normal and tumoral glial cells was
      altered from a filamentous arrangement to a mixed punctuate/filamentous pattern
      when in co-culture with neurons. Together, these results suggest that
      glioblastoma cells could identify neuronal cells as partners, to support their
      growth and induce complex neurites, but they lost the normal glia property to
      distinguish neuronal age. In addition, our results show for the first time that
      neurons modulate the organization of astrocytes and glioblastoma laminin on the
      extracellular matrix.

PMID- 17177854
TI  - Differential expression of entactin-1/nidogen-1 and entactin-2/nidogen-2 in
      myogenic differentiation.
AB  - Here, we show that entactin-2 expression is strongly, but transiently, induced in
      myogenic differentiation. Treatment of C2C12 myoblasts with actinomycin D in
      parallel to the induction of differentiation could demonstrate that this is due
      to enhanced transcription of the entactin-2 gene. Furthermore, treatment with the
      translation inhibitor cycloheximide could show that entactin-2 is a primary
      response gene. As p38 MAP kinase is an important regulator of myogenic
      differentiation, we also analyzed the possibility that entactin-2 might be a
      target of this pathway. However, using various p38 MAPK inhibitors, we could not
      detect involvement of p38 in entactin-2 up-regulation. Most remarkably,
      expression of the entactin-2 homolog entactin-1 dramatically declined in
      myogenesis, suggesting different functions of the two entactins in this process.
      A similar effect was seen in primary myoblasts isolated from two different mouse
      strains. Expression of high levels of entactin-1 in myoblasts using a retroviral
      expression system led to a higher proliferation rate both in growth and in
      differentiation medium and to reduced expression of various myogenic
      differentiation markers after the induction of differentiation. Furthermore,
      decreased expression of the entactin-2 gene after treatment of the cells with ent
      2-specific siRNA preparation led to reduced expression of the cell cycle
      inhibitor p21. These data suggest important and distinct functions of entactin-1
      and -2 in myogenic differentiation.

PMID- 17177852
TI  - Cyclic strain induces expression of specific smooth muscle cell markers in human
      endothelial cells.
AB  - The objective of this study was to determine whether cyclic strain could promote
      human umbilical vein endothelial cells (HUVECs) to express markers in common with
      the mature smooth muscle cell (SMC) phenotype, suggesting endothelial cell to SMC
      transdifferentiation. HUVECs were cultured on stretched membranes at 10% stretch
      and 60 cycles/min for 24-96 hr, and demonstrated elongation with enhanced and
      organized F-actin distribution. By using real-time polymerase chain reaction
      analysis, the mRNA levels of five specific SMC markers, SM22-alpha, alpha-smooth
      muscle actin (alpha-SMA), caldesmon-1, smooth muscle myosin heavy chain (SMMHC),
      and calponin-1 were significantly increased in cyclic strain-treated HUVECs as
      compared with those in static control cells. Protein levels of SM22-alpha and
      alpha-SMA were also substantially increased by Western blot and
      immunofluorescence staining. In addition, two specific endothelial markers, von
      Willebrand factor (vWF) and vascular endothelial growth factor receptor-2 (VEGFR
      2), showed a reduction in mRNA expression. In addition, cyclic strain-induced
      increase of SM22-alpha and alpha-SMA expression were reversible when cells were
      cultured back to the static condition. These results demonstrate a possible
      endothelial cell to SMC transdifferentiation in response to cyclic strain.
      Hemodynamic forces in modulating endothelial phenotype may play an important role
      in the vascular system.

PMID- 17177856
TI  - Trishanku, a novel regulator of cell-type stability and morphogenesis in
      Dictyostelium discoideum.
AB  - We have identified a novel gene, trishanku (triA), by random insertional
      mutagenesis of Dictyostelium discoideum. TriA is a Broad complex Tramtrack bric-a
      brac domain-containing protein that is expressed strongly during the late G2
      phase of cell cycle and in presumptive spore (prespore (psp)) cells. Disrupting
      triA destabilizes cell fate and reduces aggregate size; the fruiting body has a
      thick stalk, a lowered spore: stalk ratio, a sub-terminal spore mass and small,
      rounded spores. These changes revert when the wild-type triA gene is re-expressed
      under a constitutive or a psp-specific promoter. By using short- and long-lived
      reporter proteins, we show that in triA(-) slugs the prestalk (pst)/psp
      proportion is normal, but that there is inappropriate transdifferentiation
      between the two cell types. During culmination, regardless of their current fate,
      all cells with a history of pst gene expression contribute to the stalk, which
      could account for the altered cell-type proportion in the mutant.

PMID- 17177855
TI  - Disruption of the ifkA and ifkB genes results in altered cell adhesion,
      morphological defects and a propensity to form pre-stalk O cells during
      development of Dictyostelium.
AB  - IfkA and ifkB are two GCN2-like genes present in Dictyostelium. Disruption of
      either gene alone results in subtle developmental defects. However, disruption of
      ifkA and ifkB within the same strain results in severe morphological and
      patterning defects in the developing double null cells. The mutant cells
      aggregate in streams that give tightly clumped mounds. Fingers form from the
      mounds but remain attached to one another, especially at their bases. The fingers
      culminate to give fused and entangled structures lacking proper stalk but
      containing some spores. The morphological defects are consistent with an enhanced
      cell-cell and cell-substrate adhesiveness of the developing double null cells,
      which may result in inappropriate cell contacts and altered cell motility and
      sorting properties. In ifkA/ifkB nulls, cell type proportioning and patterning is
      altered in favor of ALC/pstO cell types. The bias toward the ALC/pstO cell types
      may be due, in part, to the nuclear localization of the transcription factor
      STATc in growing ifkA/ifkB null cells. STATc normally becomes localized to the
      nucleus during finger formation and only within the pre-stalk O zone. The
      precocious nuclear localization seen in the mutant cells may predispose the cells
      to a ALC/pstO cell fate. The findings indicate that IfkA and IfkB have redundant
      functions in Dictyostelium morphogenesis that involve maintaining proper cell
      cell and cell-substrate adhesion and the equilibrium between different cell types
      for proper spatial patterning.

PMID- 17177857
TI  - Blown fuse regulates stretching and outgrowth but not myoblast fusion of the
      circular visceral muscles in Drosophila.
AB  - Circular visceral muscles of Drosophila are binuclear syncytia arising from
      fusion of two different kinds of myoblasts: a circular visceral founder cell and
      one visceral fusion-competent myoblast. In contrast to fusion leading to the
      somatic body-wall musculature, myoblast fusion for the circular visceral muscles
      does not result in massive syncytia but instead in syncytia interconnected with
      multiple cytoplasmic bridges, which differentiate into large web-shaped muscles.
      Here, we show that these syncytial circular visceral muscles build a gut
      enclosing network with the interwoven longitudinal visceral muscles. At the
      ultrastructural level, during circular visceral myoblast fusion and the first
      step of somatic myoblast fusion prefusion complexes and electron-dense plaques
      were not detectable which was surprising as these structures are characteristic
      for the second step of somatic myoblast fusion. Moreover, we demonstrate that
      Blown fuse (Blow), a cytoplasmic protein essential for the second step of somatic
      myoblast fusion, plays a different role in circular visceral myogenesis. Blow is
      known to be essential for progression beyond the prefusion complex in the somatic
      mesoderm; however, analysis of blow mutants established that it has a restricted
      role in stretching and outgrowth of the syncytia in the circular visceral
      muscles. Furthermore, we also found that in the visceral mesoderm, Blow is
      expressed in both the fusion-competent myoblasts and circular visceral founders,
      while expression in the somatic mesoderm is initially restricted to fusion
      competent myoblasts. We also demonstrate that different enhancer elements in the
      first intron of blow are responsible for this distinct expression pattern. Thus,
      we propose a model for Blow in which this protein is involved in at least two
      clearly differing processes during Drosophila muscle formation, namely somatic
      myoblast fusion on the one hand and stretching and outgrowth of circular visceral
      muscles on the other.

PMID- 17177858
TI  - Organotypic co-cultures allow for immortalized human gingival keratinocytes to
      reconstitute a gingival epithelial phenotype in vitro.
AB  - We report here that the organotypic co-culture (OCC) system allows for
      significant preservation of the tissue-specific phenotype of human gingival
      keratinocytes (IHGK) immortalized with the E6/E7 gene of the human papillomavirus
      type 16 (HPV16). The approach adopted is based on the OCC system facilitating
      spatially separated cell growth and cell-to-cell interactions via diffusible
      growth factors. Generally, IHGK reveal transcription of the HPV16 E6/E7 gene at
      rising passages. Fluorescence in situ hybridization performed for chromosomes 1,
      8, 10, and 18 demonstrates that disomic fractions differ between the tested
      chromosomes but otherwise remain fairly constant. Monosomies of chromosome 18 are
      more prominent in late passages 81 and 83, while polysomies of chromosome 10 and
      18 are detected in early passages 25 and 27. In comparison with corresponding
      monolayer cultures (MCs), IHGK in OCCs form stratified epithelia, proliferate,
      and express gingival-specific gene products in vitro. Moreover, mRNA gene
      transcription for growth factors interleukin 1beta, granulocyte-macrophage colony
      stimulating factor, fibroblast growth factor 7, and EGF in OCCs is different from
      that in MCs. When grafted onto nude mice, IHGK develop hyperplastic,
      differentiated surface epithelia devoid of malignant growth. We are not aware of
      any other OCC system comprising of IHGK, which allows for site-specific
      expression of gingival epithelial markers. This substantiates reconstitution of a
      gingival epithelial phenotype in vitro.

PMID- 17177860
TI  - Carboxypeptidase E in the mouse placenta.
AB  - Carboxypeptidase E (CPE) has important functions in processing of endocrine pro
      peptides, such as pro-insulin, pro-opiomelanocortin, or pro-gonadotropin
      releasing hormone, as evidenced by the hyper-pro-insulinemia, obesity, and
      sterility of Cpe mutant mice. Down-regulation of Cpe in enlarged placentas of
      interspecific hybrid (interspecies hybrid placental dysplasia (IHPD)) and cloned
      mice suggested that reduced CPE enzyme and receptor activity could underlie
      abnormal placental phenotypes. In this study, we have explored the role of Cpe in
      murine placentation by determining its expression at various stages of gestation,
      and by phenotypic analysis of Cpe mutant placentas. Our results show that Cpe and
      Carboxypeptidase D (Cpd), another carboxypeptidase with a very similar function,
      are strictly co-localized in the mouse placenta from late mid-gestation to term.
      We also show that absence of CPE causes a sporadic but striking placental
      phenotype characterized by an increase in giant and glycogen cell numbers and
      giant cell hypertrophy. Microarray-based transcriptional profiling of Cpe mutant
      placentas identified only a very small number of genes with altered expression,
      including Dtprp, which belongs to the prolactin gene family. Concordant
      deregulation of Cpe and Cpd in abnormal placentas of interspecies hybrids before
      the onset of IHPD phenotype and recapitulation of some phenotypes of IHPD
      hyperplastic placentas in Cpe mutant placentas suggests that these two genes are
      causally involved in IHPD and may function as speciation genes in the genus Mus.

PMID- 17177859
TI  - Rho kinase acts at separate steps in ureteric bud and metanephric mesenchyme
      morphogenesis during kidney development.
AB  - In this study, five different in vitro assays, which together recapitulate much
      of kidney development, were used to examine the role of the Rho-associated
      protein serine/threonine kinase (ROCK) in events central to ureteric bud (UB) and
      metanephric mesenchyme (MM) morphogenensis, in isolation and together. ROCK
      activity was found to be critical for (1) cell proliferation, growth, and
      development of the whole embryonic kidney in organ culture, (2) tip and stalk
      formation in cultures of isolated UBs, and (3) migration of MM cells (in a novel
      MM migration assay) during their condensation at UB tips (in a UB/MM
      recombination assay). Together, the data indicate selective involvement of
      Rho/ROCK in distinct morphogenetic processes necessary for kidney development and
      that the coordination of these events by Rho/ROCK provides a potential mechanism
      to regulate overall branching patterns, nephron formation, and thus, kidney
      architecture.

PMID- 17177861
TI  - Rescue of morphogenetic defects and of retinoic acid signaling in retinaldehyde
      dehydrogenase 2 (Raldh2) mouse mutants by chimerism with wild-type cells.
AB  - Retinoic acid (RA), the active vitamin A derivative, is an important
      developmental signaling molecule in vertebrates. In this study, we have assessed
      whether minimal numbers and/or specific distributions of RA-producing cells can
      support normal mouse embryonic development. Retinaldehyde dehydrogenase 2
      (RALDH2) is the main RA-synthesizing enzyme acting during development. We have
      generated an embryonic stem (ES) cell line homozygous for an Raldh2 gene
      disruption, and have analyzed chimeric embryos with various contributions of wild
      type cells. Whereas embryos almost completely derived from Raldh2(-/-) cells
      phenocopy the corresponding germline null mutants, the presence of even small
      numbers (<10%) of wild-type cells can rescue most of the morphogenetic defects,
      including embryonic turning and axial elongation, and left-right looping of the
      heart tube. No consistent bias in the distribution of wild-type cells was
      observed in the phenotypically rescued Raldh2(-/-) chimeras. Analysis of an RA
      sensitive transgene indicates that RA can diffuse from wild-type cells and elicit
      a widespread transcriptional response in Raldh2-deficient cells. Our results show
      that few wild-type RA-producing cells, even when present in apparent random
      distributions, can support early morphogenesis of the mouse embryo. However, the
      Raldh2(-/-) chimeric fetuses display lung abnormalities, persistent truncus
      arteriosus, and abnormal myocardial differentiation, showing that subsequent RA
      dependent events cannot be fully rescued by the mosaic presence of wild-type
      cells.

PMID- 17177863
TI  - Contribution of gender to pathophysiology and clinical presentation of IBS:
      should management be different in women?
AB  - The irritable bowel syndrome (IBS) is found more commonly in women than men. It
      is more prevalent in patients with chronic fatigue syndrome, fibromyalgia, and
      chronic pelvic pain, all syndromes characterized by pain and found predominantly
      in women. This article reviews evidence for a role of biological sex factors and
      gender on the pathways mediating visceral pain. The effect of gonadal hormones on
      gastrointestinal motility and the sensory afferent pathway and central processing
      of visceral stimuli and the contribution of gender role to the clinical
      presentation are discussed. Although differences in responses to treatment
      modalities between genders exist, the approach to IBS patients in both genders is
      quite similar. Nevertheless, a special attention to gender role and stress
      related factors should be addressed. New developments in research, outlined in
      the paper, might bring more gender-specific treatments in the future.

PMID- 17177864
TI  - Fecal Incontinence: a woman's view.
AB  - Fecal incontinence (FI) has a prevalence of 2-7% in the general community and
      increases substantially in hospitalized patients and nursing home residents.
      Incontinent patients often isolate themselves from society for fear of having an
      incontinent episode in public. Few of these patients ever discuss this ailment
      with their doctor, despite a significant increase in depression and anxiety.
      Women have gender-specific medical and surgical conditions that predispose them
      to FI such as pregnancy, scleroderma, MS, IBS, childbirth, and pelvic surgeries.
      This article will address multiple facets of FI, but will focus specifically on
      issues related to women.

PMID- 17177865
TI  - Impact of proctectomy on continence and sexual function in women.
AB  - Whether treating a patient with colorectal cancer, or inflammatory bowel disease,
      or a variety of other gastrointestinal ailments, gastroenterologists sometimes
      need to enlist the help of colorectal surgeons to treat their patients. Surgical
      resection of the rectum is a frequently preformed procedure that has changed
      significantly over the last century. We have progressed from the early twentieth
      century, when removal of the rectum and anus with a permanent colostomy was a
      revolutionary and life-saving treatment for rectal cancer, to the present era of
      rectal resection and multiple, complex options for its reconstruction. Extensive
      knowledge of the pelvic anatomy is necessary in order for surgeons to preserve
      pelvic function while excising diseased tissue. Pelvic surgery poses unique
      challenges to patients, and proctectomy can drastically affect a woman's
      continence, sexual function, and fertility. It is imperative for
      gastroenterologists to understand how proctectomy can affect their patient's
      quality of life, independent of their disease state.

PMID- 17177866
TI  - Uniquely women's issues in colorectal cancer screening.
AB  - Colorectal cancer (CRC) is the third most common cause of cancer in women.
      Screening has been shown to increase detection and decrease morbidity from this
      disease, but compliance is poor. This paper reviews special considerations for
      determining screening intervals in women, factors making screening more difficult
      in women, and studies reviewing preventative strategies in addition to screening
      that may reduce CRC.

PMID- 17177867
TI  - Treatment strategies for autoimmune hepatitis.

PMID- 17177868
TI  - Drug therapy of inflammatory bowel disease in fertile women.
AB  - Inflammatory bowel disease (IBD) is a disease that affects women of childbearing
      age. Active disease at conception increases the risk for adverse outcomes and
      thus postponement of pregnancy until the disease is in remission is the best
      advice that physicians can give their IBD patients. The majority of medications
      used to treat IBD are safe in pregnancy and breastfeeding; active, untreated, or
      undertreated disease is more deleterious than active therapy.

PMID- 17177869
TI  - Urogenital complications of Crohn's disease.
AB  - Urogenital complications in Crohn's disease is a very narrow, specific area for
      consideration. The most frequent conditions that fall under this rubric include
      fistulous disease involving the genitourinary tract, nephrolithiasis, intrinsic
      renal diseases associated with Crohn's disease, and considerations in those who
      have had surgical procedures that alter normal pelvic anatomy. Fistulas involving
      the ureters, urinary bladder, and vagina are discussed. Nephrolithiasis is
      commonly in the form of calcium oxalate and uric acid, and is a well-known
      complication of Crohn's disease secondary to multiple mechanisms. Intrinsic renal
      disease is relatively rare and includes interstitial nephritis, amyloidosis, IgA
      nephropathy, and obstructive uropathy. Women who have undergone ileopouch anal
      anastomosis procedures are at risk for sexual dysfunction, dyspareunia, and
      decreased fecundity.

PMID- 17177870
TI  - Is functional dyspepsia of particular concern in women? A review of gender
      differences in epidemiology, pathophysiologic mechanisms, clinical presentation,
      and management.
AB  - Dyspepsia is a remarkably common symptom in the general population. Although
      multiple definitions have been used to describe the symptom, the most common
      explanation is that of chronic or recurrent pain or discomfort (a subjective
      negative feeling that may be associated with early satiety, fullness, bloating,
      or nausea) centered in the upper abdomen. When a thorough evaluation of a
      dyspeptic patient fails to identify a cause for her symptoms, the label of
      nonulcer or functional dyspepsia is applied. Functional dyspepsia is a
      heterogeneous disorder characterized by relapsing and remitting symptoms.
      Treatment strategies should focus on alleviating the most bothersome symptom and
      can be based on the proposed underlying pathophysiology. The effect of gender on
      mechanisms of disease, symptom presentation, and treatment response is an area of
      increasing interest and study. As with other functional gastrointestinal
      disorders, there appear to be some gender-specific features of functional
      dyspepsia. Specifically, gender-related differences have been observed in some
      studies of both the prevalence of individual dyspepsia symptoms, and in gastric
      emptying and proximal gastric motor function. There also appear to be gender
      differences in the psychosocial realm, with dyspeptic women experiencing a lesser
      sense of well-being than dyspeptic men, as well as an association of an abuse
      history with functional dyspepsia. This review will highlight specific gender
      differences related to the symptom presentation, pathophysiology, and approach to
      treatment of functional dyspepsia, while noting where differences have not been
      found and where further investigation is warranted.

PMID- 17177871
TI  - Seasonal variation in heat shock proteins Hsp70 and Hsp90 expression in an
      exposed and a shaded habitat of Iris pumila.
AB  - Seasonal variation in heat shock proteins Hsp70 and Hsp90 expression was studied
      in the leaves of two naturally growing Iris pumila populations, one inhabiting an
      open dune site, and the other the understorey of a Pinus silvestris stand. The
      Hsps were quantified by an immunoblotting procedure. The level of the Hsps was
      found to vary significantly both across seasons and between habitats. The mean
      Hsp70 concentration was significantly greater at the open area than in the
      woodland understorey, reaching its maximum in the summer, especially in plants
      experiencing full sunlight. Two Hsp90 isoforms, referred to as Hsp90a (86 kDa)
      and Hsp90b (84 kDa), were detected. At both habitats, the level of Hsp90a was
      highest in autumn, that of Hsp90b in spring, whereas both of them reached a nadir
      in summer. Throughout the growing season, the relative abundance of Hsp90b was
      higher in plants growing under vegetation canopy in comparison to those
      inhabiting the open dune site. An inverse relationship between the phenotypic
      variation in specific leaf area and the level of Hsp90b over seasons at both
      habitats was observed, suggesting the role of this protein in buffering
      phenotypic variation in the wild.

PMID- 17177872
TI  - Resistance to CO2 diffusion in cuticular membranes of amphibious plants and the
      implication for CO2 acquisition.
AB  - Cuticular membranes (CMs) were isolated from leaves of amphibious and submerged
      plants and their CO2 resistances were determined as a contribution to establish
      quantitatively the series of resistances met by CO2 diffusing from bulk water to
      the chloroplasts of submerged leaves. The isolation was performed enzymatically;
      permeabilities were determined and converted to resistances. The range of
      permeance values was 3 to 43 x 10(-6) m s(-1) corresponding to resistance values
      of 23 to 295 x 10(3) s m(-1), i.e. of the same order of magnitude as boundary
      layer resistances. The sum of boundary layer, CM, leaf cell and carboxylation
      resistances could be contained within the total diffusion resistance as
      determined from the photosynthetic CO2 affinity of the leaf. From the same
      species, the aerial leaf CM resistance was always higher than the aquatic leaf CM
      resistance. In a terrestrial plant, the CM resistance to CO2 diffusion was found
      lower in leaves developed submerged.

PMID- 17177873
TI  - Anisohydric but isohydrodynamic: seasonally constant plant water potential
      gradient explained by a stomatal control mechanism incorporating variable plant
      hydraulic conductance.
AB  - Isohydric and anisohydric regulations of plant water status have been observed
      over several decades of field, glasshouse and laboratory studies, yet the
      functional significance and mechanism of both remain obscure. We studied the
      seasonal trends in plant water status and hydraulic properties in a natural stand
      of Eucalyptus gomphocephala through cycles of varying environmental moisture
      (rainfall, groundwater depth, evaporative demand) in order to test for isohydry
      and to provide physiological information for the mechanistic interpretation of
      seasonal trends in plant water status. Over a 16 month period of monitoring,
      spanning two summers, midday leaf water potential (psi(leaf)) correlated with
      predawn psi(leaf), which was correlated with water table depth below ground
      level, which in turn was correlated with total monthly rainfall. Eucalyptus
      gomphocephala was therefore not seasonally isohydric. Despite strong stomatal
      down-regulation of transpiration rate in response to increasing evaporative
      demand, this was insufficient to prevent midday psi(leaf) from falling to levels
      below -2 MPa in the driest month, well into the region likely to induce xylem air
      embolisms, based on xylem vulnerability curves obtained in the study. However,
      even though midday psi(leaf) varied by over 1.2 MPa across seasons, the
      hydrodynamic (transpiration-induced) water potential gradient from roots to
      shoots (delta psi(plant)), measured as the difference between predawn and midday
      psi(leaf), was relatively constant across seasons, averaging 0.67 MPa. This
      unusual pattern of hydraulic regulation, referred to here as isohydrodynamic, is
      explained by a hydromechanical stomatal control model where plant hydraulic
      conductance is dependent on transpiration rate.

PMID- 17177874
TI  - Inhibition of root elongation by ethylene in wetland and non-wetland plant
      species and the impact of longitudinal ventilation.
AB  - The slow gas diffusion rate in flooded soil not only causes oxygen deficiency,
      but also favours the accumulation of ethylene in root systems to concentrations
      that may strongly affect root elongation. Previously published experiments showed
      that root elongation in rice is much less strongly inhibited by ethylene than in
      some other species less well adapted to wet conditions. Rice roots have also been
      reported to produce abnormally little ethylene. We tested if these traits are
      typical of wetland species and are thus likely to be widespread adaptive traits.
      Comparisons using 14 species indicated that insensitivity to the inhibiting
      effects of ethylene on root elongation is unlikely to be a common feature of
      temperate wetland species. However, resistance to longitudinal gas diffusion
      within roots of wetland species, which largely depends on diameter and the
      presence of gas-filled channels, was found to be less than in non-wetland
      species. We show that this can help maintain low internal ethylene concentrations
      by venting accumulated gas to the shoot and atmosphere.

PMID- 17177875
TI  - Expression of a nitric oxide degrading enzyme induces a senescence programme in
      Arabidopsis.
AB  - Nitric oxide (NO) has been proposed to act as a factor delaying leaf senescence
      and fruit maturation in plants. Here we show that expression of a NO degrading
      dioxygenase (NOD) in Arabidopsis thaliana initiates a senescence-like phenotype,
      an effect that proved to be more pronounced in older than in younger leaves. This
      senescence phenotype was preceded by a massive switch in gene expression in which
      photosynthetic genes were down-regulated, whereas many senescence-associated
      genes (SAGs) and the 1-aminocyclopropane-1-carboxylic acid (ACC) synthase gene
      ACS6 involved in ethylene synthesis were up-regulated. External fumigation of NOD
      plants with NO as well as environmental conditions known to stimulate endogenous
      NO production attenuated the induced senescence programme. For instance, both
      high light conditions and nitrate feeding reduced the senescence phenotype and
      attenuated the down-regulation of photosynthetic genes as well as the up
      regulation of SAGs. Treatment of plants with the cytokinin 6-benzylaminopurin
      (BAP) reduced the down-regulation of photosynthesis, although it had no
      consistent effect on SAG expression. Metabolic changes during NOD-induced
      senescence comprehended increases in salicylic acid (SA) levels, accumulation of
      the phytoalexin camalexin and elevation of leaf gamma-tocopherol contents, all of
      which occurred during natural senescence in Arabidopsis leaves as well. Moreover,
      NO fumigation delayed the senescence process induced by darkening individual
      Arabidopsis Columbia-0 (Col-0) leaves. Our data thus support the notion that NO
      acts as a negative regulator of leaf senescence.

PMID- 17177876
TI  - High temperature acclimation of C4 photosynthesis is linked to changes in
      photosynthetic biochemistry.
AB  - With average global temperatures predicted to increase over the next century, it
      is important to understand the extent and mechanisms of C4 photosynthetic
      acclimation to modest increases in growth temperature. To this end, we compared
      the photosynthetic responses of two C4 grasses (Panicum coloratum and Cenchrus
      ciliaris) and one C4 dicot (Flaveria bidentis) to growth at moderate (25/20
      degrees C, day/night) or high (35/30 degrees C, day/night) temperatures. In all
      three C4 species, CO2 assimilation rates (A) underwent significant thermal
      acclimation, such that when compared at growth temperatures, A increased less
      than what would be expected given the strong response of A to short-term changes
      in leaf temperature. Thermal photosynthetic acclimation was further manifested by
      an increase in the temperature optima of A, and a decrease in leaf nitrogen
      content and leaf mass per area in the high- relative to the moderate-temperature
      grown plants. Reduced photosynthetic capacity at the higher growth temperature
      was underpinned by selective changes in photosynthetic components. Plants grown
      at the higher temperature had lower amounts of ribulose-1,5-bisphosphate
      carboxylase/oxygenase and cytochrome f and activity of carbonic anhydrase. The
      activities of photosystem II (PSII) and phosphoenolpyruvate carboxylase were not
      affected by growth temperature. Chlorophyll fluorescence measurements of F.
      bidentis showed a corresponding decrease in the quantum yield of PSII (phi(PSII))
      and an increase in non-photochemical quenching (phi(NPQ)). It is concluded that
      through these biochemical changes, C4 plants maintain the balance between the
      various photosynthetic components at each growth temperature, despite the
      differing temperature dependence of each process. As such, at higher temperatures
      photosynthetic nitrogen use efficiency increases more than A. Our results suggest
      C4 plants will show only modest changes in photosynthetic rates in response to
      changes in growth temperature, such as those expected within or between seasons,
      or the warming anticipated as a result of global climate change.

PMID- 17177877
TI  - Regulation and manipulation of ABA biosynthesis in roots.
AB  - Overexpression of 9-cis-epoxycarotenoid dioxygenase (NCED) is known to cause
      abscisic acid (ABA) accumulation in leaves, seeds and whole plants. Here we
      investigated the manipulation of ABA biosynthesis in roots. Roots from whole
      tomato plants that constitutively overexpress LeNCED1 had a higher ABA content
      than wild-type (WT) roots. This could be explained by enhanced in situ ABA
      biosynthesis, rather than import of ABA from the shoot, because root cultures
      also had higher ABA content, and because tetracycline (Tc)-induced LeNCED1
      expression caused ABA accumulation in isolated tobacco roots. However, the Tc
      induced expression led to greater accumulation of ABA in leaves than in roots.
      This demonstrates for the first time that NCED is rate-limiting in root tissues,
      but suggests that other steps were also restrictive to pathway flux, more so in
      roots than in leaves. Dehydration and NCED overexpression acted synergistically
      in enhancing ABA accumulation in tomato root cultures. One explanation is that
      xanthophyll synthesis was increased during root dehydration, and, in support of
      this, dehydration treatments increased beta-carotene hydroxylase mRNA levels.
      Whole plants overexpressing LeNCED1 exhibited greatly reduced stomatal
      conductance and grafting experiments from this study demonstrated that this was
      predominantly due to increased ABA biosynthesis in leaves rather than in roots.
      Genetic manipulation of both xanthophyll supply and epoxycarotenoid cleavage may
      be needed to enhance root ABA biosynthesis sufficiently to signal stomatal
      closure in the shoot.

PMID- 17177878
TI  - Distinct roles of electric and hydraulic signals on the reaction of leaf gas
      exchange upon re-irrigation in Zea mays L.
AB  - The hypothesis that electric and hydraulic long-distance signals modify
      photosynthesis and stomatal aperture upon re-irrigation in intact drought
      stressed plants was examined. Maize plants (Zea mays L.) were exposed to drought
      conditions by decreasing the soil water content to 40-50% of field capacity. The
      decrease in water content resulted in a decline in stomatal conductance to 50-60%
      of the level in well-watered plants. Re-irrigation of the plants initiated both
      hydraulic and electric signals, followed by a two-phase response of the net CO2
      uptake rate and stomatal conductance of leaves. The transitional first phase
      (phase 1) is characterized by a rapid decrease in both levels. In the second
      phase (phase 2), both parameters gradually increase to levels above those of
      drought-stressed plants. Elimination of either the hydraulic signal by
      compensatory pressure application to the root system, or of the electric signal
      by cooling of the leaf blade gave evidence that the two signals (1) propagated
      independently from each other and (2) triggered the two-phase response in leaf
      gas exchange. The results provided evidence that the hydraulic signal initiated a
      hydropassive decrease in stomatal aperture and for the involvement of electric
      signals in the regulation of photosynthesis of drought-stressed plants.

PMID- 17177879
TI  - Genome-wide reprogramming of metabolism and regulatory networks of Arabidopsis in
      response to phosphorus.
AB  - Affymetrix ATH1 arrays, large-scale real-time reverse transcription PCR of
      approximately 2200 transcription factor genes and other gene families, and
      analyses of metabolites and enzyme activities were used to investigate the
      response of Arabidopsis to phosphate (Pi) deprivation and re-supply. Transcript
      data were analysed with MapMan software to identify coordinated, system-wide
      changes in metabolism and other cellular processes. Phosphorus (P) deprivation
      led to induction or repression of > 1000 genes involved in many processes. A
      subset, including the induction of genes involved in P uptake, the mobilization
      of organic Pi, the conversion of phosphorylated glycolytic intermediates to
      carbohydrates and organic acids, the replacement of P-containing phospholipids
      with galactolipids and the repression of genes involved in nucleotide/nucleic
      acid synthesis, was reversed within 3 h after Pi re-supply. Analyses of 22 enzyme
      activities revealed that changes in transcript levels often, but not always, led
      to changes in the activities of the encoded enzymes in P-deprived plants.
      Analyses of metabolites confirmed that P deprivation leads to a shift towards the
      accumulation of carbohydrates, organic acids and amino acids, and that Pi re
      supply leads to use of the latter. P-deprived plants also showed large changes in
      the expression of many genes involved in, for example, secondary metabolism and
      photosynthesis. These changes were not reversed rapidly upon Pi re-supply and
      were probably secondary in origin. Differentially expressed and highly P-specific
      putative regulator genes were identified that presumably play central roles in
      coordinating the complex responses of plants to changes in P nutrition. The
      specific responses to Pi differ markedly from those found for nitrate, whereas
      the long-term responses during P and N deprivation share common and non-specific
      features.

PMID- 17177880
TI  - Assessing environmental and physiological controls over water relations in a
      Scots pine (Pinus sylvestris L.) stand through analyses of stable isotope
      composition of water and organic matter.
AB  - This study investigated the influence of meteorological, pedospheric and
      physiological factors on the water relations of Scots pine, as characterized by
      the origin of water taken up, by xylem transport as well as by carbon isotope
      discrimination (Delta13C) and oxygen isotope enrichment (Delta18O) of newly
      assimilated organic matter. For more than 1 year, we quantified delta2H and
      delta18O of potential water sources and xylem water as well as Delta13C and
      Delta18O in twig and trunk phloem organic matter biweekly, and related these
      values to continuously measured or modelled meteorological parameters, soil water
      content, stand transpiration (ST) and canopy stomatal conductance (G(s)). During
      the growing season, delta18O and delta2H of xylem water were generally in a range
      comparable to soil water from a depth of 2-20 cm. Long residence time of water in
      the tracheids uncoupled the isotopic signals of xylem and soil water in winter.
      Delta18O but not Delta13C in phloem organic matter was directly indicative of
      recent environmental conditions during the whole year. Delta18O could be
      described applying a model that included 18O fractionation associated with water
      exchange between leaf and atmosphere, and with the production of organic matter
      as well as the influence of transpiration. Phloem Delta13C was assumed to be
      concertedly influenced by G(s) and photosynthetically active radiation (PAR) (as
      a proxy for photosynthetic capacity). We conclude that isotope signatures can be
      used as effective tools (1) to characterize the seasonal dynamics in source and
      xylem water, and (2) to assess environmental effects on transpiration and G(s) of
      Scots pine, thus helping to understand and predict potential impacts of climate
      change on trees and forest ecosystems.

PMID- 17177881
TI  - Physiological girdling of pine trees via phloem chilling: proof of concept.
AB  - Quantifying below-ground carbon (C) allocation is particularly difficult as
      methods usually disturb the root-mycorrhizal-soil continuum. We reduced C
      allocation below ground of loblolly pine trees by: (1) physically girdling trees
      and (2) physiologically girdling pine trees by chilling the phloem. Chilling
      reduced cambium temperatures by approximately 18 degrees C. Both methods rapidly
      reduced soil CO2 efflux, and after approximately 10 days decreased net
      photosynthesis (P(n)), the latter indicating feedback inhibition. Chilling
      decreased soil-soluble C, indicating that decreased soil CO2 efflux may have been
      mediated by a decrease in root C exudation that was rapidly respired by microbes.
      These effects were only observed in late summer/early autumn when above-ground
      growth was minimal, and not in the spring when above-ground growth was rapid. All
      of the effects were rapidly reversed when chilling was ceased. In fertilized
      plots, both chilling and physical girdling methods reduced soil CO2 efflux by
      approximately 8%. Physical girdling reduced soil CO2 efflux by 26% in non
      fertilized plots. This work demonstrates that phloem chilling provides a non
      destructive alternative to reducing the movement of recent photosynthate below
      the point of chilling to estimate C allocation below ground on large trees.

PMID- 17177882
TI  - Synthesis of novel peptide inhibitors of thrombin-induced platelet activation.
AB  - Inhibitors of the activation of platelet aggregation have promise as important
      therapeutic agents for the management of acute coronary syndrome (ACS). Platelet
      activation by thrombin, a serine protease, occurs by binding to and cleavage of
      the extracellular N-terminal domains of protease-activated receptors 1 and 4
      (PAR1 and PAR4). The proteolysis of the PARs exposes new tethered ligands that
      then signal through transmembrane domains to initiate platelet activation as a
      downstream effect. A pentapeptide cleavage product of bradykinin with the
      sequence Arg-Pro-Pro-Gly-Phe serves as a thrombin inhibitor by blocking alpha-
      and gamma-thrombin-induced platelet aggregation. Analogs of RPPGF have been
      prepared that result in improved inhibition of thrombin activation of platelets.
      Specific amino acid residues required for activity against platelet aggregation
      have been identified, and a lead compound, rOicPaPhe(p-Me)-NH(2) (FM19), has been
      developed. FM19, which completely inhibits threshold gamma-thrombin-induced
      platelet aggregation at a concentration of 16 +/- 4 microm, represents an
      important lead compound in the development of inhibitors of thrombin-mediated
      platelet aggregation for treatment of ACS.

PMID- 17177883
TI  - Interactions between conserved residues in transmembrane helices 2 and 7 during
      angiotensin AT1 receptor activation.
AB  - Site-directed mutagenesis studies and independent molecular modeling studies were
      combined to investigate the network of inter-residue interactions within the
      transmembrane region of the angiotensin AT(1a) receptor. Site-directed
      mutagenesis was focused on residues Tyr292, Asn294, Asn295, and Asn298 in
      transmembrane helix 7, and the conserved Asp74 in helix 2 and other polar
      residues. Functional interactions between pairs of residues were evaluated by
      determining the effects of single and double-reciprocal mutations on agonist
      induced AT(1a) receptor activation. Replacement of Tyr292 by aspartate in helix 7
      abolished radioligand binding to both Y292D and D74Y/Y292D mutant receptors.
      Reciprocal mutations of Asp74/Asn294, Ser115/Asn294, Ser252/Asn294, and
      Asn298/Sen115 caused additive impairment of function, suggesting that these pairs
      of residues make independent contributions to AT(1a) receptor activation. In
      contrast, mutations of the Asp74/Tyr298 pair revealed that the D74N/N298D
      reciprocal mutation substantially increased the impaired inositol phosphate
      responses of the D74N and N298D receptors. Extensive molecular modeling yielded
      3D models of the TM region of the AT(1) receptor and the mutants as well as of
      their complexes with angiotensin II, which were used to rationalize the possible
      reasons of impairing of function of some mutants. These data indicate that Asp74
      and Asn298 are not optimally positioned for direct strong interaction in the
      resting conformation of the AT(1a) receptor. Balance of interactions between
      residues in helix 2 (as D74) and helix 7 (as N294, N295 and N298) in the AT(1)
      receptors, however, has a crucial role both in determining their functional
      activity and levels of their expression.

PMID- 17177884
TI  - 1-(Azolyl)-4-(aryl)-phthalazines: novel potent inhibitors of VEGF receptors I and
      II.
AB  - Novel potent derivatives of phthalazine are described as an adenosine
      triphosphate-competitive inhibitors of vascular endothelial growth factor
      receptors I and II. A number of compounds display vascular endothelial growth
      factor receptor II inhibitory activity reaching that of Vatalanib A (IC(50): < 50
      nm) in an homogenous time-resolved fluorescence enzymatic assay.

PMID- 17177885
TI  - Novel O-superfamily conotoxins identified by cDNA cloning from three vermivorous
      Conus species.
AB  - The O-superfamily of conotoxins includes several subfamilies with different
      pharmacological targets, all of which are voltage-gated ion channels and
      distributed widely in varied Conus species. The venom components from any Conus
      species are quite distinct from those of other species. Seven novel O-superfamily
      peptides were identified by cDNA cloning from the three vermivorous Conus species
      of C. betulinus, C. lividus and C. caracteristicus native to Hainan. They share
      three common signal sequences, and a conserved arrangement of cysteine residues
      (C-C-CC-C-C). Phylogenetic analysis of newly found conotoxins in this study and
      known homologue O-superfamily sequences from the other Conus species was
      performed systematically. Divergence and percentage identity of the amino acid
      sequences of the signal regions suggest that the novel conotoxins described in
      this investigation belong to the three broad clades: MSGL, ME-QK and MKLT, each
      of which has its own characteristic signature signal sequence and cysteine codon
      conservation. Relative to this work, it is noted that O-superfamily conotoxins
      are not well represented from vermivorous species. The elucidated cDNAs of these
      newly found vermivorous toxins would facilitate a better understanding for basic
      research and drug discovery.

PMID- 17177886
TI  - Identification of human dim1 as a peptidase with autocleavage activity.
AB  - Dim1 is a highly conserved splicing factor. It is encoded by an essential gene in
      fission yeast and the Caenorhabditis elegans. It may also be involved in tissue
      specific or pathway-specific alternative splicing. Here, we report that besides
      its function in pre-mRNA splicing, human dim1 is a peptidase and has autocleavage
      activity. Its autocleavage results in a thioredoxin-like core that was shown
      previously to act as a dominant negative in fission yeast. The truncated form
      retains its peptidase activity. Future studies will be needed to identify
      residues important for dim1-peptidase activity and to characterize its substrate
      specificity. The biologic importance of dim1's peptidase function and its natural
      substrate(s) also need to be determined. However, if one or more of its
      substrates is involved in the pathogenesis of a human disease, dim1 may become a
      new target for drug development.

PMID- 17177887
TI  - Convenient method for monitoring Abeta aggregation by quartz-crystal
      microbalance.
AB  - We have found that a quartz-crystal microbalance is a facile and useful tool for
      detecting the specific aggregation of the amyloid-beta peptides responsible for
      Alzheimer's disease. This method greatly reduces the time and samples
      (corresponds to 1 Hz frequency decrease per 30 pg mass increase on a 4.9 mm(2)
      electrode) that are needed in the aggregation assay, and is also applicable to
      molecular interactions between smaller amyloid-beta fragment peptides such as the
      pentapeptide KLVFF.

PMID- 17177888
TI  - The indirect generation of long-distance structural changes in antibodies upon
      their binding to antigen.
AB  - An allosteric mechanism for the generation of long-distance structural
      alterations in Fab fragments of antibodies in immune complexes has been
      postulated and tested in theoretical and experimental analysis. The flexing
      and/or torsion-derived forces exerted on the elbow region in Fab arms of bivalent
      antibodies upon binding to antigen were assumed to drive the disruption of
      hydrogen bonds which stabilize N- and C-terminal chain fragments in V-domains.
      This allows an extra movement in the elbow followed by a relaxation in the Fab
      arm and may generate long-distance effects if, in particular, the structural
      changes are generated asymmetrically involving one chain of the Fab arm only.
      This mechanism was studied by simulation of molecular dynamics. The local
      instability in the area involving the site of packing of the N-terminal chain
      fragment allows penetration and binding of the supramolecular dye Congo red that
      hence becomes an indicator of the initiated relaxation process and is also the
      prospective ligand in studies of designing drugs. The susceptibility to dye
      binding was observed in complexation of bivalent antibodies only, supplying the
      evidence that constraints associating the interaction with randomly distributed
      antigenic determinants drive the local structural changes in the V-domain
      followed by long-distance effects.

PMID- 17177889
TI  - Characterization of tachykinin-related peptides from different insect species on
      Drosophila tachykinin receptor-expressing cell line.
AB  - Drosophila tachykinin receptor, a neurokinin receptor cloned from the fruit fly
      Drosophila melanogaster, is a G-protein-coupled receptor, which upon activation
      by a peptide agonist induces a transient increase in the concentration of
      intracellular calcium. The functional assay based on aequorin-derived
      luminescence triggered by receptor-mediated changes in Ca(2+) levels was used to
      examine and compare the effect of tachykinin-related peptides from different
      species. Among the endogenous Drosophila peptides, Drm-TK I induced the strongest
      calcium response. The most potent tachykinin-related peptides from Leucophaea
      maderae, Locusta migratoria, and Calliphora vomitoria, were partial agonists at
      the Drosophila tachykinin receptor.

PMID- 17177891
TI  - Alternate binding mode of C-terminal phenethylamine analogs of G(t)alpha(340-350)
      to photoactivated rhodopsin.
AB  - The C-terminus of the Galpha-subunit of transducin plays an important role in
      receptor recognition. Synthetic peptides corresponding to the last 11 residues of
      the subunit have been shown to stabilize the photoactivated form of rhodopsin,
      Rh*. The Rh*-bound structure of the G(t)alpha(340-350) peptide has been
      determined using transferred nuclear overhauser effect NMR. In that structure, we
      observed two interactions between Lys341 and Phe350, a cation-pi interaction
      between the epsilon-amine and the aromatic ring of Phe350 and a salt-bridge
      between the epsilon-amine and the C-terminal carboxylate. A series of C-terminal
      phenethylamine analogs of the G(t)alpha(340-350) peptide were synthesized,
      lacking the C-terminal carboxylate group, to investigate the forces that
      contribute to the stability of the Rh*-bound conformation of the peptide. Rh*
      stabilization assay data suggest that the C-terminal carboxylate is not necessary
      to maintain binding affinity. Transferred nuclear overhauser effect NMR
      experiments reveal that these C-terminal phenethylamine peptides adopt an Rh*
      bound structure that is similar overall, but lacking some of the intramolecular
      interactions observed in the native Rh*-bound G(t)alpha(340-350) structure. These
      studies suggest that the binding site for G(t)alpha(340-350) on Rh* is adaptable,
      and we propose that the charged carboxylate of Phe350 does not play a significant
      role in the interaction with Rh*, but helps stabilize the Rh*-bound confirmation
      of the native peptide.

PMID- 17177892
TI  - 4-(Azolylphenyl)-phthalazin-1-amines: Novel inhibitors of VEGF receptors I and
      II.
AB  - Novel potent derivatives of phthalazine are described as ATP-competitive
      inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2).
      A number of compounds display VEGFR-2 inhibitory activity reaching that of
      Vatalanib 3 (IC50 < 100 nm) in an HTRF enzymatic assay. Several derivatives also
      show good potential for the development as VEGFR-2 specific inhibitors showing 15
      20-fold selectivity over VEGFR-1.

PMID- 17177893
TI  - Influence of generation 2-5 of PAMAM dendrimer on the inhibition of Tat peptide/
      TAR RNA binding in HIV-1 transcription.
AB  - The special binding of Tat protein to TAR RNA leads to the transcription of HIV-1
      virus. In this study, the influence of 2-5 generation of PAMAM dendrimers on the
      inhibition of Tat protein/TAR RNA binding has been investigated. The absorption
      of PAMAM dendrimers on TAR RNA, fixed on a gold substrate through an avidin
      biotion connection, was carried out by using a quartz crystal microbalance.
      Experimental result shows a Langmuir-type isotherm could be used to describe this
      kind of binding, implying a specific and monolayer adsorption existed. The
      combination coefficient (K(D)(-1))s can be calculated according to Langmuir
      Equation, having the order of G3 > G4 > G5 >Tat > G2, indicating that PAMAM G3,
      G4 and G5 having the possibility to be the inhibitors of HIV-1 transcription. The
      migration time (T(migra)) of capillary electrophoretic technique has the same
      sequence as (K(D)(-1))s. These two parameters could be used as simple and
      quantitative criteria for the selection of possible drugs from numerous
      candidates for HIV therapy in vitro.

PMID- 17177894
TI  - Radiolabeling and in vitro and in vivo characterization of [18F]FB-[R(8,15,21),
      L17]-VIP as a PET imaging agent for tumor overexpressed VIP receptors.
AB  - In an effort to develop a peptide-based radiopharmaceutical for the detection of
      tumors overexpressed vasoactive intestinal peptide receptors with positron
      emission tomography, we have prepared a novel [R(8,15,21), L17]-VIP peptide for
      18F-labeling. This peptide inhibited 125I-VIP binding to rats lung membranes with
      high affinity [half-maximal inhibitory concentrations (IC50) of 0.12 nm].
      Additionally, [R(8,15,21), L17]-VIP showed higher stability than native
      vasoactive intestinal peptide in vivo of mice. With N-succinimidyl 4-[18F]
      fluorobenzoate as labeling prosthetic group, [18F]FB-[R(8,15,21), L17]-VIP was
      obtained in >99% radiochemical purity within 100 min in decay-for-corrected
      radiochemical yield of 33.6 +/- 3% (n = 5) and a specific radioactivity 255
      GBq/micromol at the end of synthesis. Stability of [18F]FB-[R(8,15,21), L17]-VIP
      in vitro and in vivo were investigated. Biodistribution of this trace was carried
      out in mice with induced C26 colorectal tumor. Fast clearance of [18F]FB
      [R(8,15,21), L17]-VIP from non-target tissues and specific uptakes by tumors
      realized higher tumor-to-muscle ratio (3.55) and tumor-to-blood ratio (2.37) 60
      min postinjection. Clear difference was observed between the blocking and
      unblocking experiments in biodistribution and whole body radioautography. [18F]FB
      [R(8,15,21), L17]-VIP has demonstrated its potential for diagnosing tumors
      overexpressed vasoactive intestinal peptide receptors both in vitro and in vivo.

PMID- 17177895
TI  - Peptides by extension at the N- or C-terminii of lysine.
AB  - Dipeptides 3a-g, (3a + 3a'), (3d + 3d'), (3l + 3l')a and tripeptides 6a-e, (6b +
      6b'), (6e + 6e') incorporating Z(epsilon)-Lys were prepared in high yields (70
      95%) and enantiopurity (> or =97%) in partially aqueous acetonitrile solution by
      coupling using (i) Z(epsilon)-Lys with N-(Z- and Fmoc-aminoacyl)benzotriazoles 1a
      g, (ii) Z(epsilon)-Lys with N-Z-dipeptidoylbenzotriazoles 5a-c, and (iii) N
      Fmoc(alpha)-Z(epsilon)-l-Lys-Bt 1h and amino acids 2a,c-e. Unnatural dipeptides
      3h-j, (3h + 3h') and tripeptides 6f were similarly prepared from Z(alpha)-Lys.
      Retention of chirality was demonstrated by parallel experiments involving l-Ala,
      dl-Ala, l-Met, and dl-Met by NMR and HPLC analysis.

PMID- 17177896
TI  - Synthesis and in vitro evaluation of novel 2-oxo-1,2-dihydroquinoline CB2
      receptor inverse agonists.
AB  - Aliphatic amides of 7-methoxy-2-oxo-8-pentyloxy-1,2-dihydroquinoline-3-carboxylic
      acid 6 were synthesized and evaluated for their CB2 and CB1 receptor activities
      by a [35S]GTPgammaS membrane-binding assay. Compounds 7-18 produced CB2 inverse
      agonist activities with a variety of potencies (IC50: 1 nm-1 microm). By
      contrast, no considerable antagonism of CB1 receptor was observed by 1-10 microm
      concentrations indicating that synthesized compounds were CB2 receptor selective.

PMID- 17177897
TI  - Synthesis and biological activity of seleno sunflower trypsin inhibitor analog.
AB  - Sunflower trypsin inhibitor (SFTI-1) is a cyclic peptide with 14 amino acid
      residues and one disulfide bond. Its synthetic acyclic analog (aSFTI-1) with N
      terminal Gly and C-terminal Asp was still active. Here, we report the synthesis
      of seleno aSFTI-1 with the disulfide bond of aSFTI-1 replaced by diselenide bond.
      The formation of the diselenide bond from selenol was achieved in a single step
      without the aid of oxidizing agent. For comparison, aSFTI-1 itself and aSFTI-1
      with its disulfide bond replaced by two serines ([Ser(3,11)] aSFTI-1) were also
      synthesized. The trypsin inhibitory constants of seleno aSFTI-1, aSFTI-1 and
      [Ser(3,11)] aSFTI-1 were determined as 6.50 x 10(-9), 1.96 x 10(-9) and 8.10 x
      10(-6) respectively, indicating that the disulfide bond is essential for the
      structure and function of aSFTI-1, and seleno aSFTI-1 is still active, although
      its inhibitory constant is reduced to 30% in comparison with that of aSFTI-1.

PMID- 17177898
TI  - Cancer screening.

PMID- 17177899
TI  - The effectiveness of commonly used mouthwashes for the prevention of chemotherapy
      induced oral mucositis: a systematic review.
AB  - Daily chlorhexidine mouthwash is often recommended for preventing chemotherapy
      induced oral mucositis. Povidone-iodine, NaCl 0.9%, water salt soda solution and
      chamomile mouthwash are also recommended. However, the effectiveness of these
      mouthwashes is unclear. Therefore, we performed a systematic review to assess the
      effectiveness of mouthwashes in preventing and ameliorating chemotherapy-induced
      oral mucositis. Based on study quality, three out of five randomized controlled
      trials were included in a meta-analysis. The results failed to detect any
      beneficial effects of chlorhexidine as compared with sterile water, or NaCl 0.9%.
      Patients complained about negative side-effects of chlorhexidine, including teeth
      discoloration and alteration of taste in two of the five studies on
      chlorhexidine. The severity of oral mucositis was shown to be reduced by 30%
      using a povidone-iodine mouthwash as compared with sterile water in a single
      randomized controlled trial. These results do not support the use of
      chlorhexidine mouthwash to prevent oral mucositis.

PMID- 17177901
TI  - Health literacy: more choice, but do cancer patients have the skills to decide?
AB  - As health care moves towards greater choice, with shared responsibility and
      decision making between doctors and patients, a variety of resources and skills
      are needed by individuals if they are to be active participants in their health.
      Health literacy is the ability to make the most out of health. For an individual,
      it is the capacity to obtain, interpret and understand basic health information
      and services in ways that enhance health. In developed countries, however, over
      half of the population have reading and comprehension difficulties, creating a
      gap between the educational expectations of health-care services and an
      individual's ability to understand. This review highlights the difficulty many
      cancer patients face as a consequence of their poor literacy and comprehension
      skills. It draws attention to a problem whose magnitude is not always easy to
      recognize and suggests simple ways health professionals can more effectively
      communicate with their patients.

PMID- 17177900
TI  - Social objectives in cancer care: the example of palliative day care.
AB  - Social objectives are poorly specified and evaluated in cancer care. Palliative
      day care is an example where social objectives are often identified but research
      has focused on health-care outcomes. A literature review identifies four types of
      social objective: emotional and spiritual care, general social care, services for
      families and carers and creative arts. Social objectives include: distinguishing
      between therapeutic work and leisure and supportive interventions, promoting
      service continuity, reducing social isolation, increasing social interaction,
      reassuring introduction to palliative care, rehearsal of reactions to illness
      with a sympathetic audience, integration of families and carers into care
      services, respite for carers and creative work for three separable objectives. It
      is argued that interventions to achieve social objectives may be defined and
      evaluated in a measurable way. Similarly, social objectives and interventions can
      be specified at other stages in the cancer journey.

PMID- 17177902
TI  - A series of bed exercises to improve lymphocyte count in allogeneic bone marrow
      transplantation patients.
AB  - The purpose of this study was to investigate the effect of a series of bed
      exercises on lymphocyte and T-cell subsets in allogeneic bone marrow
      transplantation patients during hospitalization. Thirty-five patients were
      randomly assigned, with 18 assigned to an exercise group and 17 to a control
      group. The bed exercise intervention was applied by a nurse to the exercise group
      for 30 min every day for 6 weeks. Patients in the exercise group had a mean
      increase of 40.9 lymphocyte cells/microL and patients in the control group had a
      mean decrease of 640.7 lymphocyte cells/microL. There were no significant
      differences in the percentage of cluster of differentiation (CD)3+, CD4+ and
      CD8+, and CD4+/CD8+ ratio between the two groups. These findings indicate that
      bed exercise could be an effective nursing intervention with patients undergoing
      bone marrow transplantation by increasing the lymphocyte count during
      hospitalization.

PMID- 17177903
TI  - Effect of rehabilitation facility location on outcomes in head and neck surgical
      patients.
AB  - The objective of this study was to determine the significance of in-hospital
      rehabilitation facility vs. distant rehabilitation facilities in the outcomes and
      complications of post-operative head and neck surgical patients. Retrospective
      review of head and neck surgical patients was conducted over a 5-year period at a
      tertiary care medical centre. Fifty patients met criteria for this study (35
      males, 15 females). Forty-two patients had a primary squamous cell carcinoma and
      eight patients had other primary malignancies of the head and neck. Thirty-two
      patients were placed in an in-hospital rehabilitation facility and 18 patients
      were placed in distant rehabilitation facilities (average distance 40.9 miles).
      Seventeen patients (34%) had complications including infection/drainage (seven
      patients), fistula (six patients), pneumonia (two patients), wound dehiscence
      (two patients) and other minor complications. The difference complication rate
      among the two groups was not statistically significant (37.5% in-hospital
      rehabilitation, 27.8% distant rehabilitation; P=0.496). The rate of hospital re
      admission was not statistically significant (25% in-hospital rehabilitation
      patients, 16.7% distant rehabilitation patients; P=0.505). The average length of
      stay of patients without complications was 18.5 days (SD=5.8) for in-hospital
      rehabilitation and 12.9 days (SD=17) for distant rehabilitation. This difference
      was not statistically significant (P=0.346). In summary, one-third of post
      operative head and neck surgical patients developed complications while in a
      rehabilitation facility. The length of stay, hospital re-admission rate and
      frequency of complications does not correlate with the proximity of the
      rehabilitation facility to the hospital where the patients received their
      surgery.

PMID- 17177904
TI  - Botryoid rhabdomyosarcoma of the biliary tract in children: a unique case report.
AB  - Rhabdomyosarcoma (RMS) is the most common tumour of the biliary tree in
      childhood. In children, it is a rare lesion, accounting for about 1% of all RMS.
      Hepatobiliary botryoid RMS is a disease affecting young children at a median age
      of about 3 years. In literature, the radiological findings of hepatobiliary RMS
      have been described in small series and some case reports. In this case report,
      we present a rare case of RMS of the extrahepatic biliary tree initially
      diagnosed as a choledochal cyst.

PMID- 17177905
TI  - How acceptable is a referral and telephone-based outcall programme for men
      diagnosed with cancer? A feasibility study.
AB  - The objective of this study was to determine the feasibility and acceptability of
      a referral and outcall programme from a telephone-based information and support
      service, for men newly diagnosed with colorectal or prostate cancer. A block
      randomized controlled trial was performed involving 100 newly diagnosed
      colorectal and prostate cancer patients. Patients were referred to the Cancer
      Information Support Service (CISS) through clinicians at diagnosis. Clinicians
      were randomized into one of three conditions. Active referral 1: specialist
      referral with four CISS outcalls: (1)<or=1 week of diagnosis; (2) at 6 weeks; (3)
      3 months; and (4) 6 months post diagnosis. Active referral 2: specialist referral
      with one CISS outcall<or=1 week of diagnosis. Passive referral: specialist
      recommended patient contacts CISS, but contact at the patient's initiative.
      Patients completed research questionnaires at study entry (before CISS contact),
      then 4 and 7 months post diagnosis. Overall, 96% of participants reported a
      positive experience with the referral process; 87% reported they were not
      concerned about receiving the calls; and 84% indicated the timing of the calls
      was helpful. In conclusion, the referral and outcall programme was achievable and
      acceptable for men newly diagnosed with colorectal or prostate cancer.

PMID- 17177906
TI  - Improving cancer patients' pain: the impact of the hospital specialist palliative
      care team.
AB  - Pain is reported to occur in the majority of patients with advanced cancer and is
      one of the main reasons for referral to a hospital specialist palliative care
      team. Yet despite this, there is a paucity of research into the impact the
      hospital specialist palliative care team has on pain control in patients. A non
      equivalent control group design using a quota sample investigated 100 cancer
      patients who had been admitted to hospital for symptom control. Fifty patients
      received specialist hospital palliative care team intervention compared with 50
      patients receiving traditional care. Outcome was assessed using the Palliative
      Care Assessment (PACA) tool on three occasions. There was no difference between
      the groups on the initial assessment and the results indicated that all cancer
      patients admitted to hospital had a significant improvement in their pain
      control. However, the patients who had the additional input of the palliative
      care team demonstrated a statistically significant greater improvement than the
      control group (P<0.001). Potential explanations are made for the results
      including the enhanced knowledge and skills of the hospital specialist palliative
      care team.

PMID- 17177907
TI  - Religious coping and problem-solving by couples faced with prostate cancer.
AB  - Religion can be an important resource for people struggling with chronic illness.
      Problem-solving skills have also been shown to be helpful. This study examined
      whether turning to religion as a coping resource would be associated with better
      problem-solving in couples trying to manage challenges associated with prostate
      cancer. The sample was 101 patients with prostate cancer and their wives. Wives
      completed the Social Problem-Solving Inventory--Revised at baseline (T1) and 10
      weeks later (T2). Patients and their wives also completed a measure that included
      items on religious coping. These items were used to classify couples into four
      groups based on whether one or both members engaged in religious coping: (1)
      husband only, (2) wife only, (3) both husband and wife, and (4) neither husband
      nor wife. From T1 to T2, wives who used religious coping along with their
      husbands (group 3) showed a significantly greater reduction in dysfunctional
      problem-solving (specifically, on impulsive/careless problem-solving) in
      comparison with wives who used religious coping while their husbands did not
      (group 2). Findings suggest that when couples share in turning to religion as a
      source of coping, this may be associated with improved problem-solving, but sole
      engagement in religious coping by wives may be associated with worse problem
      solving.

PMID- 17177908
TI  - What women want: convenient appointment times for cervical screening tests.
AB  - Little is known about women's preferred appointment times for cervical screening
      tests. Data from a postal questionnaire survey were used to compare preferred
      appointment times with those given. Although 33.4%[95% confidence intervals (CI)
      31.8%-35.0%] of respondents received appointments between 10h00 and 11h55, only
      17.0% (95% CI 15.3%-18.7%) wanted an appointment at that time. Nineteen per cent
      (95% CI 17.4%-21.0%) of respondents wanted appointments between 18h00 and 20h00,
      but only 4.4% (95% CI 3.7%-5.1%) received them. Saturday appointments for
      cervical screening are not given; however, overall approximately 13% of those
      surveyed would have preferred a Saturday appointment. Preferred times also varied
      significantly with age and deprivation category. Further research is required to
      determine whether appointment times for cervical screening can be tailored to
      meet these expressed needs, and the impact this has on service provision and
      uptake.

PMID- 17177909
TI  - Human immunodeficiency virus-associated diffuse non-Hodgkin's lymphoma in
      Venezuelan patients: treatment with full-dose cyclophosphamide-doxorubicin
      vincristine-prednisone without routine use of granulocyte-colony stimulating
      factor.
AB  - The routine use of granulocyte-colony stimulating factor (G-CSF) for 10 days
      during full-dose cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)
      chemotherapy in HIV-associated diffuse non-Hodgkin's lymphoma (NHL) patients is
      very expensive in developing countries. We treated 22 HIV-associated diffuse NHL
      patients with standard-dose CHOP and used G-CSF after an episode of febrile
      neutropenia until neutrophil count reached 1000/mm3. The clinical response was:
      complete response (36%), partial response (32%), stable disease (14%) and
      progression (18%). There were no toxicity-related deaths. Grade 3 or 4
      neutropenia was observed in 16% of cycles, but only 8% were complicated with
      febrile neutropenia. Seventeen patients died (median survival 15 months; range 2
      70). There are five patients alive (median survival 24+ months; range 17-36+).
      Our experience showed that we can treat HIV-related NHL patients with full-dose
      CHOP, achieve good responses and have an acceptable toxicity profile, with the
      use of G-CSF as needed.

PMID- 17177910
TI  - Malignant spinal cord compression in cancer patients may be mimicked by a primary
      spinal cord tumour.
AB  - Although it is quite rare, second primary neoplasms in cancer patients may
      present with the signs and symptoms of malignant spinal cord compression. Primary
      spinal cord tumours in the cancer patients may be deceptive and considered as the
      recurrent first cancer. Therefore, it should be precisely differentiated and
      appropriately managed. We report such a case of intramedullary ependymoma of the
      cervical spinal cord mimicking metatstatic recurrent lymphoma and causing cord
      compression. A 50-year-old man developed intramedullary ependymoma of the
      cervical spinal cord 1.5 years following chemoradiation for Waldeyer's ring
      lymphoma. He presented with a 2-month history of neck pain, progressive upper-
      and lower-extremity numbness and weakness, and bowel and bladder dysfunction.
      Magnetic resonance imaging revealed an intramedullary expansive lesion extending
      from C4 to C6 levels of the cervical spinal cord. The clinical and radiological
      findings were suggestive of malignant process. A comprehensive investigation
      failed to detect another site of disease. He underwent operation, and the tumour
      was subtotally resected. The patient's neurological deficits improved
      subsequently. The development of the intramedullary ependymoma following treating
      lymphoma has not been reported. We describe the clinical, radiological and
      pathological findings of this case and review the literature.

PMID- 17177913
TI  - Long-term cancer survivors: 'who is there to work with these people?'.

PMID- 17177914
TI  - Effective integration of complementary therapies in cancer and palliative care.

PMID- 17177915
TI  - Foundations for self-awareness: An exploration through autism.
AB  - Developmental psychopathology holds promise for elucidating the structure of self
      awareness. Here we studied social emotions in matched groups of children and
      adolescents with and without autism. Our aims were to determine whether there are
      potentially dissociable aspects of self-awareness, and to reconsider how the
      qualities of young children's engagement with other persons influences the
      development of their sense of self. Parent interviews yielded evidence that
      children with autism are limited in social-relational and emotional domains of
      self-awareness; for example, few were reported to show guilt, embarrassment, or
      shame. Yet according to parent report, most were affected by the moods of others,
      showed some degree of pity and concern, and manifested jealousy. When presented
      with videotaped scenes, participants with autism were similar to those without
      autism in identifying pride, guilt, and shame, and they were able to describe
      their own experiences of pride and, more rarely, guilt. In situations designed to
      elicit emotions, participants with autism were rated as showing pride, but they
      manifested lesser degrees and atypical qualities of guilt and coyness. Relatively
      few showed personal forms of self-consciousness when asked to pose for a
      photograph. We argue that in order for children to achieve depth in self
      awareness, and to relate to themselves as occupying a distinctive stance within a
      framework of mutual self-other relatedness, they need to identify with the
      attitudes of other people. We interpret the present studies in terms of
      dissociations among three forms of social emotion: "person-centered" qualities of
      relational self-awareness that require identification and are specifically
      limited among children with autism, more diffuse modes of relational self
      consciousness, and a third group of social emotions, epitomized by jealousy,
      situated in a separate developmental line. We propose a rebalancing of emotion
      theory that gives greater prominence to children's developing forms of
      interpersonal and intra-psychic relatedness.

PMID- 17177924
TI  - Subjectivity, identification and differentiation: Key issues in early social
      development.

PMID- 17177927
TI  - Is using an evidence-based clinical management tool sufficient for implementing
      evidence-based practice?

PMID- 17177928
TI  - Adoption of a ventilator-associated pneumonia clinical practice guideline.
AB  - CONCEPTUAL FRAMEWORK: The Academic Center for Evidence-based Practice (ACE) Star
      Model was used to implement an evidence-based clinical practice guideline (CPG)
      in order to decrease ventilator-associated pneumonia (VAP) incidence rates and
      ventilator days. The goal was to interrupt person-to-person transmission of
      bacteria and bacterial colonization using low-cost, evidence-based strategies to
      prevent VAP. DISCOVERY: Two geographically proximate medical centers, inclusive
      of five intensive care units located in the southwestern region of the United
      States had significant variations in their VAP rates. EVIDENCE SUMMARY: Using the
      U.S. Preventive Services Task Force grading criteria, the results of 69 studies
      were used to establish a clinical practice guideline to prevent ventilator
      associated pneumonia. TRANSLATION: A clinical practice guideline was developed
      for the prevention of VAP and included five nursing activities: (a) head-of-bed
      elevation; (b) oral care; (c) ventilator tubing condensate removal; (d) hand
      hygiene; and (e) glove use. The effect of the CPG, inclusive of an educational
      intervention, was measured using an observational, prospective, quasi
      experimental design. INTEGRATION: A multidisciplinary education team developed a
      self-learning packet, educational materials, and storyboards for the staff as
      dissemination strategies. Strategies also included e-mail, one-on-one teaching
      with clinicians, and feedback on guideline adoption and VAP rate reports.
      EVALUATION: Observation data were collected to evaluate adoption of the CPG while
      caring for 106 ventilated patients. VAP rates changed at both hospitals although
      the change was not statistically significant. Additionally, the ICU length of
      stay declined at both facilities, causing cost savings. DISCUSSION: These results
      support the idea that adoption of evidence-based practices contributes to
      decreased VAP rates. For a successful program, ICU leaders should emphasize
      strategies that routinize adoption of evidence-based CPGs.

PMID- 17177929
TI  - Understanding work contextual factors: a short-cut to evidence-based practice?
AB  - BACKGROUND: It has become increasingly clear that workplace contextual factors
      make an important contribution to provider and patient outcomes. The potential
      for health care professionals of using research in practice is also linked to
      such factors, although the exact factors or mechanisms for enhancing this
      potential are not understood. From a perspective of implementing evidence-based
      nursing practice, the authors of this article report on a study examining
      contextual factors. AIM: The objective of this study was to identify predictors
      of organizational improvement by measuring staff perceptions of work contextual
      factors. METHOD: The Quality Work Competence questionnaire was used in a repeated
      measurement survey with a 1-year break between the two periods of data
      collection. The sample consisted of 134 employees from four neonatal units in
      Sweden. FINDINGS: Over the study period significant changes occurred among staff
      perceptions, both within and between units, on various factors. Changes in staff
      perceptions on skills development and participatory management were the major
      predictors of enhanced potential of overall organizational improvement. Perceived
      improvement in skills development and performance feedback predicted improvement
      in leadership. Change in commitment was predicted by perceived decreases in work
      tempo and work-related exhaustion. CONCLUSIONS AND IMPLICATIONS: These findings
      indicate the potential for organizational improvement by developing a learning
      and supportive professional environment as well as by involving staff in decision
      making at the unit level. Such initiatives are also likely to be of importance
      for enhanced use of research in practice and evidence-based nursing. On the other
      hand, high levels of work tempo and burnout appear to have negative consequences
      on staff commitment for improving care and the work environment. A better
      understanding of workplace contextual factors is necessary for improving the
      organizational potential of getting research into practice and should be
      considered in future implementation projects.

PMID- 17177930
TI  - Health promotion in the practice setting: findings from a review of clinical
      issues.
AB  - BACKGROUND: Many agencies over the last few decades have called for the explicit
      inclusion and application of health promotion in all aspects of nursing practice.
      This article reviews the body of empirical (research-based) and theoretical
      (conceptual) literature addressing health promotion in nursing clinical practice,
      to uncover its nature, intention, and impact. APPROACH: The aim of this review
      was to identify from the nursing literature what is reported on in relation to
      health promotion activity, both theoretical and clinical in the practice setting.
      An extensive review identified that literature pertaining to these issues
      clustered around the categories of: theorising and conceptualising the meaning
      and purpose of health promotion in nursing practice, the development and testing
      of tools and models for practice, and the exploration of attitudes, behaviours,
      roles and functions of nurses and health professionals in practice. FINDINGS:
      Against more recent trends in health promotion, the literature shows that broader
      and wide-ranging health promotion reform has yet to have universal impact,
      whereas conventional health education activities remain the mainstay for the
      majority of "health promotion" activities in nursing practice. Where nurses
      purport to be conducting "health promotion" they are often conducting
      behavioural, lifestyle, and risk-orientated health education. The findings of
      this review therefore support the notion that much of nursing-related health
      practice is firmly located in reactive ill health and disease risk-specific
      preventive locations, instead of incorporating and instilling broader societal,
      economic, ecological, and political dimensions of health promotion.
      Recommendations for wider reform, developed from personal opinion and supported
      by the literature, are presented. CONCLUSIONS: It is argued that nursing bodies,
      as well as individual nurses themselves, should seek current health promotion
      locations in nursing practice, and find effective ways to implement health
      promotion strategies and, subsequently, equip practitioners with the necessary
      resources and skills to engage with other health promotion agencies. Future
      research should be aimed at implementing and evaluating broad health promotion
      processes.

PMID- 17177931
TI  - Meningococcal meningitis prevention programs for college students: a review of
      the literature.
AB  - BACKGROUND AND PURPOSE: The incidence of meningococcal meningitis in college
      students is higher than in other populations. College students, especially 1st
      year students living in dormitories or residence halls, are among those at
      highest risk of developing the disease. It is estimated that immunization can
      prevent up to 83% of cases among adolescents and college students. A review of
      the literature was undertaken to identify and critique the research-based
      prevention programs that are focused on college students. METHOD: An extensive
      search of the Cochrane Database of systematic reviews, Medline, PubMed, and
      CINAHL was undertaken. The Journal of American College Health was hand searched,
      and bibliographies were reviewed for studies not otherwise identified. Four
      publications met the search criteria. These studies were reviewed and graded for
      level of evidence. FINDINGS: One study could not be compared with the other three
      because of its lack of detail. Of the other three studies, two were descriptive
      and factors were identified that related to vaccination and nonvaccination in the
      college student population (both Evidence Grade C). Only one study was described
      that included an educational intervention, which resulted in increased
      vaccination rates in a college student population (Evidence Grade B). CONCLUSIONS
      AND IMPLICATIONS: The published literature is severely limited in the area of
      meningococcal meningitis prevention programs in the at-risk college student
      population. A critical need exists for controlled studies to test the
      interventions that are most effective in this population as well as broader-based
      studies to further identify those students at increased risk for the disease as
      well as for nonvaccination.

PMID- 17177932
TI  - Teaching EBP: implementation of evidence: moving from evidence to action.

PMID- 17177935
TI  - Non-infectious granulomatous dermatitis: a clinicopathological study.
AB  - BACKGROUND: Granulomatous dermatitis frequently presents a diagnostic challenge
      to dermatopathologists because an identical histologic picture is produced by
      several causes, and conversely, a single cause may produce varied histologic
      patterns. METHODS: A retrospective analysis of skin biopsies received over a
      period of 7 years was performed, and cases of non-infectious granulomatous
      dermatitis diagnosed on histopathological examination were retrieved. RESULTS:
      Out of a total of 586 cases of granulomatous dermatitis, 71 cases (12.11%) were
      categorized as non-infectious granulomatous dermatitis on the basis of
      clinicopathological findings. Further subcategorization was done based on
      morphology of granulomas as epithelioid granulomas; 15 cases of sarcoidosis,
      21.1%, one case of Crohn's vulvitis, 1.4%, necrobiotic granulomas; 11 cases of
      granuloma annulare, 15.4%, two cases of rheumatoid nodule, 2.8%, 10 cases of
      foreign body granulomas, 14.0%; 32 cases of miscellaneous group, 45%.
      CONCLUSIONS: Morphology alone is seldom specific and cannot be used as a
      diagnostic tool for identification of specific diseases. Adequate clinical data
      and work up in combination of pathological resources can help in elucidation of
      specific etiology of granulomatous dermatitis. Mohan H, Bal A, Dhami GP. Non
      infectious granulomatous dermatitis: a clinicopathological study.

PMID- 17177936
TI  - Clinical spectrum and histological analysis of 32 cases of specific cutaneous
      sarcoidosis.
AB  - BACKGROUND: Sarcoidosis is a multisystem granulomatous disorder of unknown
      aetiology in which skin involvement is frequent. OBJECTIVE: To review
      histological characteristics of biopsies of specific cutaneous lesions of
      sarcoidosis and their relationship with clinical course. PATIENTS AND METHODS:
      Biopsies from 32 patients with specific cutaneous sarcoidosis were reviewed.
      Histological findings and clinical characteristics of these patients were
      analysed. RESULTS: The initial clinical lesions of the patients were ten
      infiltrated nodule-plaques, eight papules, four maculopapular eruptions, five
      scar sarcoidosis, four subcutaneous nodules and one lupus pernio. Sarcoidal
      granulomas were located at dermis in 31 cases (74%) and at subcutaneous fat in 12
      (28%) but only four were subcutaneous exclusively. Perivascular or periannexial
      distribution of granulomas was observed in eight cases (19%) and they had
      coalescence in 29 samples. The presence of foreign material was demonstrated in
      11 cases (26%). CONCLUSIONS: Clinical spectrum of specific lesions of cutaneous
      sarcoidosis showed a good correlation with granulomas localization in the
      biopsies. However, traditional classification of specific cutaneous sarcoidosis
      is often overlapping. On the other hand, foreign bodies and other atypical
      histological findings were more common than initially expected.

PMID- 17177937
TI  - Pathology of post-kala-azar dermal leishmaniasis: a light microscopical,
      immunohistochemical, and ultrastructural study of skin lesions and draining lymph
      nodes.
AB  - BACKGROUND: Whereas the clinical manifestations and treatment of post-kala-azar
      dermal leishmaniasis (PKDL) have been adequately described before, the pathology
      received little attention, particularly the African form of PKDL which shows some
      clinical differences from the disease in India. Therefore, our aim was to
      characterize the pathology and the immunohistopathology in PKDL lesions and
      correlate the histopathological findings with the clinical features of the
      disease. METHODS: Biopsies of skin lesions were examined for histopathological
      changes in formalin-fixed tissues and for cell phenotypes and adhesion molecules
      by immunohistochemistry. RESULTS: The epidermis showed various changes in
      different combinations. The dermis was infiltrated by lymphocytes and
      macrophages, but plasma cells were scanty or absent. The majority of cells were
      CD3 T cells, with a preponderance of CD4 over CD8 cells. Degenerating basal
      keratinocytes expressed HLA-DR, ICAM-1 and Leishmania antigen and closely
      interacted with CD4 T cells. Regional lymph nodes showed hyperplasia of the B-
      and T-cell zones. CONCLUSIONS: The inflammatory reaction in PKDL lesions is in
      response to Leishmania parasites and/or antigen. The majority of cells are CD4 T
      cells. Degeneration of the basal keratinocytes is probably due to the action of
      cytotoxic CD4 T cells interacting with leishmania-expressing epidermal cells.
      Ismail A, Gadir AFA, Theander TG, Kharazmi A, El Hassan AM. Pathology of post
      kala-azar dermal leishmaniasis: a light microscopical, immunohistochemical, and
      ultrastructural study of skin lesions and draining lymph nodes.

PMID- 17177938
TI  - Examination of bcl-2 and p53 expressions and apoptotic index by TUNEL method in
      psoriasis.
AB  - BACKGROUND: Psoriasis is characterised by hyperproliferation and by aberrant
      differentiation. Blockage of the normal apoptotic process is one of the factors
      implicated in the pathogenesis. OBJECTIVE: To determine the apoptotic features by
      using TUNEL method and also bcl-2 and p53 expressions in psoriatic epidermis.
      MATERIALS AND METHODS: Biopsies of 35 patients with psoriasis vulgaris and 14
      normal skin were evaluated. Apoptotic cells were detected using the dUTP nick-end
      labelling assay; bc1-2 and p53 expressions were assessed by using
      immunohistochemical techniques. A semi-quantitative grading system (HSCORE) was
      used for comparison. RESULTS: Bcl-2 was strongly expressed in basal keratinocytes
      of normal skin, while no expression was observed in 13 (37.2%) of the psoriatic
      samples and it was weakly expressed in the spinous cell layer of 22 (62.8%)
      samples. Moderate p53 expression was observed in the psoriasis group, while it
      was weak in the control. The percentage of TUNEL positive cells were
      significantly increased in the psoriasis group (65+/-2.30) when compared with the
      control (32.84+/-7.16). CONCLUSION: Apoptotic index besides bc1-2 and p53
      expressions in psoriasis differ from normal epidermis. Down-regulation of bc1-2
      is consistent with the dynamics of psoriasis but increased TUNEL positive cells
      and p53 expression has not been fully elucidated yet. Gunduz K, Demireli P,
      Vatansever S, Inanir I. Examination of bcl-2 and p53 expressions and apoptotic
      index by TUNEL method in psoriasis.

PMID- 17177939
TI  - Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are associated with Kaposi's sarcoma
      (KS) tumorigenesis. To date, only a few MMPs have been studied in KS lesions.
      Their role in KS regression has not been investigated. The aim of this study was
      to evaluate the expression of multiple MMPs in developing and pharmacologically
      regressed KS lesions. METHODS: Nine samples of acquired immune deficiency
      syndrome (AIDS)-related and classic cutaneous KS lesions at various histological
      stages were studied. Regressing KS lesions from three patients treated with
      systemic therapy were procured after one and two cycles of chemotherapy. Tissue
      sections from all specimens were immunostained using monoclonal antibodies to MMP
      1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-14. RESULTS: KS lesional cells
      were immunoreactive for all MMPs, except MMP-14. Admixed inflammatory cells were
      immunoreactive for MMP-1, MMP-2, MMP-7, MMP-9, and MMP-13. The MMP immunoprofile
      in residual KS lesional cells was unaltered in regressed lesions. Increased
      extracellular matrix (ECM) and macrophage immunoreactivity for MMPs was
      identified in regressed specimens. CONCLUSIONS: These data show that developing
      KS lesional cells express collagenases (MMP-1, MMP-13), gelatinases (MMP-2, MMP
      9), stromelysin-1 (MMP-3), and matrilysin (MMP-7) but not the membrane-type MMP
      14. This MMP expression profile is retained by residual KS cells and also
      expressed by infiltrating macrophages in regressed KS lesions. Pantanowitz L,
      Dezube BJ, Hernandez-Barrantes S, Tahan SR, Dabbous MK. Matrix metalloproteinases
      in the progression and regression of Kaposi's sarcoma.

PMID- 17177940
TI  - Analysis of the expression pattern of glial cell line-derived neurotrophic
      factor, neurturin, their cognate receptors GFRalpha-1 and GFRalpha-2, and a
      common signal transduction element c-Ret in the human scalp skin.
AB  - BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) and a related
      family member, neurturin (NTN), as well as their cognate receptors (GDNF
      receptors, GFRalpha-1 and GFRalpha-2, respectively) are involved in nervous
      system development and murine hair cycle control. To date, their expression in
      human scalp skin is still unknown. MATERIALS AND METHODS: The expression pattern
      of these proteins was examined in human scalp skin by immunofluorescence and
      immunoalkaline phosphatase staining methods as well as RT-PCR (GDNF). A total of
      50 normal human scalp skin biopsy specimens were examined (healthy females, 53-57
      years). RESULTS: The expression of GDNF protein was strong in the epidermis and
      sebaceous and sweat glands. In the epidermis, GDNF protein expression was seen in
      all layers except the stratum corneum. It was strong in the basal layer and
      decreased gradually towards the granular layer. The results of RT-PCR analysis
      revealed that GDNF protein is synthesised in the epidermis. The expression of
      NTN, GFRalpha-1, and GFRalpha-2 proteins was strong in the papillary dermis and
      sebaceous and sweat glands. In the epidermis, NTN protein expression was absent.
      The expression of GFRalpha-1 and GFRalpha-2 proteins was moderate in the
      epidermis. The expression of c-Ret protein was consistently strong in the
      epidermis and sebaceous and sweat glands. These proteins were strongly expressed
      in both epithelial and mesenchymal compartments of human anagen VI scalp hair
      follicles. CONCLUSIONS: Our investigation reports, for the first time, the
      expression patterns of GDNF, NTN, GFRalpha-1, GFRalpha-2, and c-Ret proteins in
      human scalp skin. The expression of these proteins in the skin suggests their
      possible roles in skin homeostasis. The clinical ramifications of these
      observations mandate further investigations. Adly MA, Assaf HA, Hussein MR, Paus
      R. Analysis of the expression pattern of glial cell line-derived neurotrophic
      factor, neurturin, their cognate receptors GFRalpha-1 and GFRalpha-2, and a
      common signal transduction element c-Ret in the human scalp skin.

PMID- 17177942
TI  - Endocrine mucin-producing sweat gland carcinoma: report of a case and review of
      the literature.
AB  - Mucinous carcinoma of skin (MCS) is an uncommon adnexal tumor of disputed
      differentiation. In 1995, Rahilly et al. reported a case of MCS with
      neuroendocrine differentiation (E-MCS). Since that report, seven additional cases
      have been published. Here, we report on a case of E-MCS and discuss the
      differential diagnoses.

PMID- 17177941
TI  - A case of argyria after colloidal silver ingestion.
AB  - BACKGROUND: Argyria is often considered an entity of the past, one which has
      largely disappeared with the cessation of silver usage in oral medications.
      However, with the practice of colloidal silver ingestion in current "alternative
      health" treatments, argyria should be considered in the differential diagnosis of
      blue-gray hyperpigmentation. METHODS: A single case report with
      clinicopathological correlation. RESULTS: Histological examination of skin biopsy
      specimen, which showed perieccrine brown-black granules, verified that colloidal
      silver rather than a prescribed medication was the source of the patient's
      dyspigmentation.

PMID- 17177944
TI  - The costs and effectiveness of information-skills training and mediated
      searching: quantitative results from the EMPIRIC project.
AB  - OBJECTIVES: To compare the effectiveness and costs of providing information for
      patient care via librarian-mediated searches and information-skills training.
      METHODS: A questionnaire survey to library staff and health professionals in the
      North West. Data was collected on perceptions of services, satisfaction and
      service usage, allowing a cost analysis to be undertaken. Statistical data was
      analysed using Statistical Package for the Social Sciences (spss). RESULTS: Using
      satisfaction and use of skills as outcome measures, both mediated searches and
      information skills training are effective. A breakdown of costs per type of
      training session and literature search is provided. Cost-effectiveness is
      dependent on whether costs are viewed from a library or trust point of view.
      Providing information skills training does not reduce the volume of mediated
      search requests. CONCLUSIONS: No one method of providing information for health
      professionals is more effective or cost-effective than another. A decision about
      which services to provide cannot be made on the basis of effectiveness or costs
      alone; the views of library staff and the health professionals they serve should
      also be taken into account. A proactive approach and targeting training towards
      those who are most likely to benefit may be an appropriate way forward.

PMID- 17177945
TI  - Two physiotherapists, one librarian and a systematic literature review:
      collaboration in action.
AB  - AIM: This paper explores the processes of collaboration between a librarian and
      two academic physiotherapists working on a systematic review jointly funded by
      the University of the West of England (UWE), Bristol, and the Royal National
      Hospital for Rheumatic Diseases (RNHRD), Bath, UK. The aim of this paper is to
      describe and evaluate some of the processes of collaboration between the three
      authors in their work in progress on a funded systematic literature review on the
      topic of hydrotherapy and pain. METHODS: The vehicle for describing and analysing
      these processes is a joint (National Health Service Trust and University) funded
      systematic literature review currently in progress on the topic of hydrotherapy
      and pain. RESULTS: Systematic review methodology is becoming increasingly complex
      and is rapidly developing its own research base. Librarian input is a key element
      in a successful systematic review. CONCLUSIONS: Systematic reviews play a
      critical role in informing healthcare delivery and research in the UK. The
      individual nature and inherent complexity of each review demands close
      collaboration between librarians, academics and clinicians. In addition to
      enhancing the reviews themselves, there are many other personal and institutional
      benefits of collaborative working. Consideration may need to be given to library
      staff structures and roles if these benefits are to be maximized and sustained.

PMID- 17177946
TI  - Information needs and information sources of individuals living with spinal cord
      injury.
AB  - AIMS AND OBJECTIVES: Access to health information is important for the well-being
      of people living in the community after spinal cord injury (SCI). In order to
      design appropriate information interventions, it is critical first to understand
      the information sources typically used. The goal of this study therefore is to
      identify the information-seeking practices of this group. SAMPLE AND METHODS: A
      sample of 207 individuals living in the community following traumatic spinal cord
      injury were surveyed regarding their ongoing information needs and practices for
      seeking information. RESULTS: The results reveal that respondents have unmet
      information needs, despite the fact that they typically access information
      through a variety of channels. SCI specialists are the most commonly used source,
      although they are viewed as relatively inaccessible. By contrast, the Internet
      (used by a relatively high proportion of respondents) is viewed as comparatively
      accessible, although there are some concerns about the quality of information
      found there. CONCLUSIONS: These survey results point to the need for an
      information source that is accessible and delivers high quality information.
      Although respondents use a variety of information sources, none meets this ideal
      profile. Information professionals should consider this gap in the design of
      information interventions.

PMID- 17177947
TI  - A pilot project of a cancer patient library in Italy: results of a customer
      satisfaction survey and its products.
AB  - AIMS: The purpose of this study is to determine the degree of satisfaction of
      users of the Cancer Information Point section of the Library for Patients (CIP
      LP), active since 1998 at the National Cancer Institute of Aviano, Italy. The CIP
      LP is based on a skilled intermediary, adequate informative material and a
      specific location, within the Scientific Library of the Institute. PATIENTS AND
      METHODS: A survey was developed to assess service functionality and quality from
      the users' viewpoint. During a 6-month period, a questionnaire was mailed to 194
      patients and relatives who previously used the CIP-LP; 113 (58%) were returned
      and processed. RESULTS: Of the respondents, 91% were pleased with the CIP-LP and
      95% would recommend the service to other people. The information obtained
      contributed to a clearer understanding of the illness and treatment (45% as first
      answer) and a better control of the situation (33%). Fifty-one per cent evaluated
      the information received as 'good', 42%'excellent' and 4%'of sufficient quality'.
      CONCLUSION: This survey shows the appreciation and usefulness in the users'
      perception of a specific hospital library for cancer patients and their
      relatives, providing an information service supplementary to doctor-patient
      communication.

PMID- 17177948
TI  - Genetic research and genetic information: a health information professional's
      perspective on the benefits and risks.
AB  - BACKGROUND: The completion of the Human Genome Project, and recent breakthroughs
      in identifying the genes both directly responsible for and contributing to the
      severity of specific diseases and disabilities in humans offer great potential
      for future health care. AIM: The aim of the paper is to inform the health
      information community of these developments in order to foster debate over their
      wide-reaching implications. METHODS: The article outlines recent research in this
      area and explains how our growing understanding opens the way for improved
      diagnosis of disease, detection of possible predisposition to specific diseases,
      the interaction between genetics and environmental aspects such as diet, as well
      as enabling gene therapy and preventative actions. This new knowledge also opens
      the way for the use of pharmacogenetic information to enhance the efficacy of
      pharmaceuticals and to avoid toxic reactions. RESULTS: These advances have
      significant social, legal and ethical implications. Most countries have limited
      legislative control over the use and protection of genetic information about
      individuals. CONCLUSION: There is a role for health information professionals to
      play in promoting wider public knowledge of genetic research and its
      implications, in fostering public debate on key issues, and in seeking clearer
      policies in the health sector concerning the use of genetic information about
      individuals.

PMID- 17177949
TI  - Widening participation in learning-developing libraries project.

PMID- 17177950
TI  - Exploring health pre-registration students use of learning resources whilst on
      clinical placement: replication of case study at Northumbria and Teesside
      Universities, UK.

PMID- 17177951
TI  - A review of health and access to health information in Bhutan.

PMID- 17177952
TI  - Designing a search strategy for locating self-help books for people with
      depression.

PMID- 17177953
TI  - The ICOH Bibliographic Database of the University of Milan, Italy: a new Internet
      resource in the field of occupational health.

PMID- 17177954
TI  - Route maps for Evidence-based problem Solutions (RESolutions): what's the
      evidence for journal cancellation?

PMID- 17177957
TI  - Crystal-ball gazing--the future of immunological research viewed from the cutting
      edge.

PMID- 17177958
TI  - C1-inhibitor concentrate home therapy for hereditary angioedema: a viable,
      effective treatment option.
AB  - Economic and political factors have led to the increased use of home therapy
      programmes for patients who have traditionally been treated in hospital. Many
      patients with hereditary angioedema (HAE) experience intermittent severe attacks
      that affect their quality of life and may be life-threatening. These attacks are
      treated with C1-inhibitor concentrate which, for most patients, is infused at the
      local hospital. Home therapy programmes for HAE are currently being established.
      This paper reviews the extent of use of these programmes and summarizes the
      advantages and potential disadvantages of the concept so far.

PMID- 17177959
TI  - Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma
      secretion and increased number of forkhead box P3-expressing cells in patients
      with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia
      exposed individuals.
AB  - Lyme borreliosis (LB) can, despite adequate antibiotic treatment, develop into a
      chronic condition with persisting symptoms such as musculoskeletal pain,
      subjective alteration of cognition and fatigue. The mechanism behind this is
      unclear, but it has been postulated that an aberrant immunological response might
      be the cause. In this study we investigated the expression of the T helper 1
      (Th1) marker interleukin (IL)-12Rbeta2, the marker for T regulatory cells,
      forkhead box P3 (FoxP3) and the cytokine profile in patients with a history of
      chronic LB, subacute LB, previously Borrelia-exposed asymptomatic individuals and
      healthy controls. Fifty-four individuals (12 chronic LB, 14 subacute LB, 14
      asymptomatic individuals and 14 healthy controls) were included in the study and
      provided a blood sample. Mononuclear cells were separated from the blood and
      stimulated with antigens. The IL-12Rbeta2 and FoxP3 mRNA expression was analysed
      with real-time reverse transcription-polymerase chain reaction (RT-PCR). The
      protein expression of IL-12Rbeta2 on CD3(+), CD4(+), CD8(+) and CD56(+) cells was
      assessed by flow cytometry. Furthermore, the secretion of interferon (IFN)-gamma,
      IL-4, IL-5, IL-10, IL-12p70 and IL-13 was analysed by enzyme-linked immunospot
      (ELISPOT) and/or enzyme-linked immunosorbent assay (ELISA). Chronic LB patients
      displayed a lower expression of Borrelia-specific IL-12Rbeta2 on CD8(+) cells and
      also a lower number of Borrelia-specific IFN-gamma-secreting cells compared to
      asymptomatic individuals. Furthermore, chronic LB patients had higher amounts of
      Borrelia-specific FoxP3 mRNA than healthy controls. We speculate that this may
      indicate that a strong Th1 response is of importance for a positive outcome of a
      Borrelia infection. In addition, regulatory T cells might also play a role, by
      immunosuppression, in the development of chronic LB.

PMID- 17177961
TI  - IL-10 produced by CD4+ and CD8+ T cells emerge as a putative immunoregulatory
      mechanism to counterbalance the monocyte-derived TNF-alpha and guarantee
      asymptomatic clinical status during chronic HTLV-I infection.
AB  - Although it is believed widely that distinct patterns of the host immune response
      are associated with the outcome of chronic human T cell lymphotropic virus type 1
      (HTLV-I) infection toward asymptomatic or symptomatic neurodegenerative
      myelopathy (HAM/TSP), the exact mechanism underlying these immunological events
      still remains unknown. In this study, we have evaluated the cytokine pattern
      [interleukin (IL)-12, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha,
      IL-4 and IL-10] of innate and adaptive immunity cells present at the peripheral
      blood from non-infected (NI) and HTLV-I infected individuals [asymptomatic (AS),
      oligosymptomatic (OL) and HAM/TSP-HT], following in vitro short-term incubation
      in the absence/presence of phorbol myristate acetate (PMA) pan-leucocyte
      stimulation. In the absence of PMA stimulation, our data demonstrate that despite
      the overall immunological profile of AS mimicry that observed for NI, the high
      frequency of IL-12(+) neutrophils and TNF-alpha(+) monocytes are also a hallmark
      of this group of individuals. However, the outstanding positive correlation
      between the high frequency of TNF-alpha(+) monocytes and high levels CD4(+) IL
      10(+) and CD8(+) IL-10(+) T cells suggests the establishment of immunoregulatory
      mechanisms that guarantee their asymptomatic clinical status. On the other hand,
      OL and HT did not present any association between the high frequency and TNF
      alpha(+) neutrophils and monocytes and this immunoregulatory profile at their
      adaptive immunity cells. Upon PMA-index analysis, high levels of type 1 CD4(+) T
      cells, as well as higher IFN-gamma/IL-10 and TNF-alpha/IL-10 ratios, were
      observed in HT, and re-emphasize the role of Th1-cytokines from CD4(+) cells to
      HTLV-I immunity and disease. Moreover, increasing frequency of CD8(+) IFN
      gamma(+) and CD8(+) TNF-alpha(+) cells were observed in the HT, which
      corroborates the marked inflammatory profile underlying this pathological
      condition and the role of CD8(+) T cells in the pathogenesis of HAM/TSP.

PMID- 17177960
TI  - Nicotine exposure alters in vivo human responses to endotoxin.
AB  - The alpha 7 nicotinic receptor is reportedly a key element in the cholinergic
      anti-inflammatory pathway. Because a prototypical ligand for this receptor is
      nicotine, we studied the in vivo human response to bacterial endotoxin or
      lipopolysaccharide (LPS) in the context of nicotine or placebo pretreatment.
      Twelve adult male normal subjects were studied prospectively. Six received
      overnight transcutaneous nicotine administration by application of a standard
      patch (7 mg). Six hours later, all subjects were given an intravenous dose of
      endotoxin (2 ng/kg) and were evaluated for an additional 24 h for circulating
      levels of inflammatory biomarkers, vital signs and symptoms. The nicotine
      subjects had elevated blood levels of the nicotine metabolite, continine, prior
      to and throughout the 24-h post-endotoxin exposure phase. Subjects receiving
      nicotine exhibited a significantly lower temperature response as well as
      attenuated cardiovascular responses for 2.5-6 h after LPS exposure. In addition,
      increased circulating interkeukin (IL)-10 and cortisol levels were also noted in
      nicotine subjects. These data indicate an alteration in LPS-induced systemic
      inflammatory responses in normal subjects exposed to transcutaneous nicotine. In
      this model of abbreviated inflammation, nicotine exposure attenuates the febrile
      response to LPS and promotes a more prominent anti-inflammatory phenotype.

PMID- 17177962
TI  - Intestinal helminth co-infection has a negative impact on both anti-Mycobacterium
      tuberculosis immunity and clinical response to tuberculosis therapy.
AB  - The impact of intestinal helminth infection on Mycobacterium tuberculosis (MTB)
      specific immune responses during active tuberculosis (TB) is not known. We
      investigated the role of intestinal helminth infection in anti-MTB immunity by
      evaluating both cellular phenotype and cytokine profiles in patients with TB and
      patients with concomitant TB and intestinal helminth infection (TB + Helm) during
      TB therapy. Twenty-seven per cent of TB patients enrolled for the study were co
      infected with at least one intestinal helminth. At baseline, absolute frequencies
      of leucocytes, monocytes and eosinophils from TB and TB + Helm patients differed
      from healthy subjects. Concomitant intestinal helminth infection in TB + Helm
      patients had a negative impact (P < 0.05) on absolute frequencies of CD3(+),
      CD4(+), CD8(+), natural killer (NK) T and CD4(+) CD25(high) T cell subsets when
      compared to either TB patients or healthy controls. Differences in CD4(+) T cell
      frequencies were accompanied by lower interferon (IFN)-gamma and elevated and
      sustained interleukin (IL)-10 levels in whole blood (WB) cultures from TB + Helm
      compared to TB patients. In addition to a depressed anti-MTB immunity, TB + Helm
      patients also presented with more severe radiological pulmonary disease, with a
      significant difference (P = 0.013) in the number of involved lung zones at the
      end of TB treatment. The above data may indicate that concomitant intestinal
      helminth infection in patients with newly diagnosed TB skews their cytokine
      profile toward a T helper 2 response, which could favour persistent MTB infection
      and a more protracted clinical course of the disease.

PMID- 17177963
TI  - Altered expression of the tetraspanin CD81 on B and T lymphocytes during HIV-1
      infection.
AB  - CD81 is a member of the tetraspan superfamily and plays a role in immune
      responses and in hepatitis C virus (HCV) pathogenesis. We analysed CD81 cell
      surface and mRNA expression in different lymphocytic subpopulations in human
      immunodeficiency virus (HIV)-1, HCV and dually infected subjects. CD81 cell
      surface expression was evaluated with fluorescence activated cell sorter (FACS)
      analysis; mRNA quantification was performed with semiquantitative polymerase
      chain reaction (PCR). CD81 cell surface expression on CD4(+) T lymphocytes was
      significantly different by analysis of variance (anova) test (P < 0.001), with
      reduced expression in HIV-1(+) patients. In B lymphocytes, higher cell surface
      expression was present in HIV-1, in HCV and in dually infected subjects compared
      to healthy controls. CD81 expression on B lymphocytes showed a positive
      correlation with plasma HIV-RNA. CD81 mRNA levels in B lymphocytes were
      significantly higher in HIV-1(+) patients compared to healthy controls. The
      potential consequence of the down-regulation of CD81 in CD4(+) cells during HIV-1
      infection in conjunction with diverted CD28, CD4 and CD3 expression is the
      disruption of T cell function. Increased CD81 expression on B lymphocytes might
      explain the higher prevalence of lymphoproliferative disorders in HIV-1 and HCV
      infection. Up-regulation of CD81 mRNA on CD4(+) T cells indicates that down
      regulation of CD81 occurs at the post-transcriptional/translational level.

PMID- 17177964
TI  - Protein array autoantibody profiles for insights into systemic lupus
      erythematosus and incomplete lupus syndromes.
AB  - The objective of this study was to investigate the prevalence and clinical
      significance of a spectrum of autoantibodies in systemic lupus erythematosus and
      incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens.
      Microarrays containing candidate autoantigens or control proteins were printed on
      16-section slides. These arrays were used to profile 93 serum samples from
      patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n =
      23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune
      controls (NC; n = 17). Data were analysed using the significance analysis of
      microarray (SAM) and clustering algorithms. Correlations with disease features
      were determined. Serum from ILE and SLE patients contained high levels of IgG
      autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens.
      Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and
      19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and
      17% of ILE samples. IgG autoantibodies segregated into seven clusters including
      two specific for DNA and RNA autoantigens that were correlated with the number of
      lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and
      histones, were correlated with renal involvement. Of the four IgM autoantibody
      clusters, two were correlated negatively with the number of lupus criteria; none
      were correlated with renal disease. The IgG : IgM autoantibody ratios generally
      showed a stepwise increase in the groups following disease burden from NC to SLE.
      Insights derived from the expanded autoantibody profiling made possible with the
      antigen array suggest differences in autoreactivity in ILE and SLE. Determining
      whether the IgM aurotreactivity that predominates in ILE represents an early
      stage prior to IgG switching or is persistent and relatively protective will
      require further longitudinal studies.

PMID- 17177965
TI  - Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion
      molecule-1) are detected in sera from patients with retinal vasculitis and are
      induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling.
AB  - Retinal vasculitis is a major component of ocular inflammation that plays a role
      in retinal tissue damage in patients with idiopathic uveitis and Behcet's
      disease. Here we show that type 1 interferons (IFN alpha/beta) were not detected
      in sera from normal individuals but were identified in up to 46% of the sera from
      retinal vasculitis patients. The predominant form of IFN observed was IFN-beta,
      which was detected in 39% of Behcet's disease patients and 47% of idiopathic
      uveitis patients. Seven patients whose sera contained IFN-beta were monitored
      prospectively. IFN-beta was shown to be present for 6-12 months in all seven of
      the sera samples tested. Furthermore, the adhesion molecule profile identified in
      this study was strikingly different when Behcet's and uveitis patient sera were
      compared to sera from normal controls. Sera from Behcet's disease patients
      contained significantly elevated levels of the soluble adhesion molecules, sE
      selectin and s-intracellular adhesion molecule-1 (sICAM-1), whereas sera from
      patients with idiopathic uveitis contained significantly increased sE-selectin.
      In vitro studies evaluating the cell source of these cytokines revealed that
      polyriboinosinic polyribocytidylic acid (poly I:C) activated retinal vascular
      endothelial cells produce sE-selectin, sICAM-1 and IFN-beta. Production of these
      molecules was inhibited by pretreatment with anti-Toll-like receptor 3 (TLR-3)
      antibody. In conclusion, IFN-beta, sE-selectin and sICAM-1 are elevated in
      patients with retinal vasculitis and are induced in retinal vascular endothelial
      cells in vitro by activating the innate immune system through TLR-3. Further
      analysis of innate immune signalling may prove to be a novel target for future
      studies on pathogenic mechanisms and therapeutic approaches in retinal
      vasculitis.

PMID- 17177966
TI  - Analysis of parotid glands of primary Sjogren's syndrome patients using proteomic
      technology reveals altered autoantigen composition and novel antigenic targets.
AB  - Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic
      infiltration, destruction of the salivary and lacrimal glands and production of
      autoantibodies against a variety of cellular proteins. The aberrant immune
      response against these autoantigens may begin or extend to other proteins that
      are not yet defined. Several studies have shown that autoantibody production is
      taking place in the affected salivary glands. In the present study, using
      proteomic approaches, we aimed to: (a) identify new autoantigens in the salivary
      glands of primary SS (pSS) patients and (b) evaluate the epigenetic changes of
      known autoantigens. Total parotid gland extracts of pSS patients were analysed
      using two-dimensional gel electrophoresis, sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis (SDS-PAGE) and immunoblot with pSS patients' sera or purified
      autoantibodies and immunoprecipitation using homologous IgG. Identification of
      the unknown proteins was performed using mass spectrometry (MS). Immunoblot
      analysis on two-dimensional gels using purified anti-La/SSB antibodies revealed
      that pSS salivary glands contain high levels of post-translationally modified
      La/SSB autoantigen, while the native form of the protein is recognized faintly,
      in contrast to normal controls. Moreover, salivary glands of pSS patients contain
      post-translationally modified actin that becomes immunogenic in the
      microenviroment of the affected tissue. The alteration of the physicochemical
      properties of self-proteins could thus contribute to the break of immune
      tolerance against them.

PMID- 17177967
TI  - Severe fibrosis in hepatitis C virus-infected patients is associated with
      increased activity of the mannan-binding lectin (MBL)/MBL-associated serine
      protease 1 (MASP-1) complex.
AB  - Mannan-binding lectin (MBL) binds microorganisms via interactions with glycans on
      the target surface. Bound MBL subsequently activates MBL-associated serine
      protease proenzymes (MASPs). A role for MBL in hepatitis C virus (HCV) infection
      had been indicated by previous studies examining MBL levels and polymorphisms in
      relation to disease progression and response to treatment. We undertook this
      study to investigate a possible relationship between disease progression and
      functional MBL/MASP-1 complex activity. A functional assay for MBL/MASP-1 complex
      activity was employed to examine serum samples from patients with chronic HCV
      infection, non-HCV liver disease and healthy controls. Intrapatient consistency
      of MBL/MASP-1 complex activity levels was assessed in sequential samples from a
      subgroup of patients. Median values of MBL/MASP-1 complex activity were higher in
      sera from patients with liver disease compared with healthy controls. MBL/MASP-1
      complex activity levels correlate with severity of fibrosis after adjusting for
      confounding factors (P = 0.003). MBL/MASP-1 complex activity was associated more
      significantly with fibrosis than was MBL concentration. The potential role of
      MBL/MASP-1 complex activity in disease progression is worthy of further study to
      investigate possible mechanistic links.

PMID- 17177968
TI  - Diclofenac induces basophil degranulation without increasing CD63 expression in
      sensitive patients.
AB  - Diclofenac (Dc) induces an IgE-independent basophil (Ba) degranulation in
      susceptible individuals. CD63 Ba expression is utilized as an in vitro test for
      diagnosis of drug hypersensitivity. We tested the ability of Dc to induce CD63 Ba
      expression by flow cytometry (BAT) and Ba degranulation using light microscopy
      (HBDT) in patients sensitive to Dc. We studied 14 patients with diclofenac
      hypersensitivity, also two patients sensitive to Dermatophagoides pteronyssinus
      (Dp), and 12 normal controls. HBDT was performed by mononuclear cells toluidine
      blue staining. BAT determined CD63 expression in antiCD63/anti-IgE/anti-CD45
      labelled whole blood. In each case, the percentage of activated Ba post
      stimulation with 1 and 10 microg/ml Dc was determined. Positive controls included
      N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide-induced activation. IgE
      mediated Ba activation was induced with a Dp allergenic extract. With Dc 1
      microg/ml, mean HBDT in Dc-susceptible individuals was 33.62 +/- 18.35% and 8.49
      +/- 4.79% in controls (P = 0.0001). Mean BAT was 2.04 +/- 1.68% and 1.93 +/-
      1.40% in controls (P = 0.8). Ba preincubation with Dc did not affect fMLP-induced
      CD63 expression, neither in Dc-sensitive individuals (P = 0.8) (n = 4) nor in
      subjects without Dc hypersensitivity (P = 0.25) (n = 4). Ba from the two patients
      sensitive both to Dc and Dp responded to Dp but not to Dc by BAT: Dc, 1.99 +/-
      0.78%; Dp: 60.87 +/- 9.28%; but showed degranulation by HBDT: Dc, 30.53 +/-
      1.02%, Dp: 48.78 +/- 22.17%. Dc induces Ba degranulation in sensitive patients in
      a way that does not induce CD63 expression and is different from IgE-mediated and
      fMLP-mediated degranulation. Our results suggest that CD63 expression is not a
      reliable diagnostic method for diclofenac allergy.

PMID- 17177969
TI  - The involvement of Fc gamma receptor gene polymorphisms in Kawasaki disease.
AB  - Kawasaki disease is an acute febrile syndrome in infancy, characterized by
      vasculitis of medium-sized arteries. Without treatment the disease can lead to
      coronary artery lesions (CAL) in approximately 25% of the children. Therapy
      consists of intravenous immunoglobulins (IVIG), leading to a decrease of
      complications to 5-16%. Little is known about the working mechanisms of IVIG. In
      this study we evaluated the involvement of Fcgamma receptors (FcgammaRs) in
      Kawasaki disease by the determination of the frequency of known single nucleotide
      polymorphisms (SNPs) in the genes coding for the FcgammaRs and compared this with
      frequencies in a cohort of healthy controls. There was no difference in the
      distribution of the functionally relevant genotypes for FcgammaRIIa-131H/R,
      FcgammaRIIb-232I/T, FcgammaRIIIa-158 V/F and FcgammaRIIIb-NA1/NA2 between the
      patient group and the healthy controls. Furthermore, there were no polymorphisms
      linked to the disease severity as indicated by the absence or development of CAL
      during the disease. Altered transcription or expression of FcgammaR on specific
      cell types of the immune system may still play a role in susceptibility and
      treatment success, but at a level different from the functional SNPs in FcgammaR
      genes tested in this study.

PMID- 17177970
TI  - Systemic inflammation alters the inflammatory response in experimental
      lipopolysaccharide-induced meningitis.
AB  - Experiments to evaluate the effect of the level and duration of endotoxaemia on
      the meningeal inflammatory response were performed in order to determine if
      systemic inflammation alters meningitis. Rabbits received either saline or
      Escherichia coli O111:B4 lipopolysacharide (LPS) intravenously at various doses
      (1, 3 or 10 microg) and times (-8, -2 or 0 h) before an intracisternal injection
      of 20 ng LPS. An intracisternal LPS injection together with saline intravenously
      produced a peak cerebrospinal fluid (CSF) tumour necrosis factor (TNF) level (95
      +/- 26 ng/ml) at 2 h and peak leucocyte level (5413 +/- 764 cells/microl) at 4 h
      post-injection. Blood leucocytes were slightly elevated (12 000 +/- 500/microl at
      0 h; 16 900 +/- 280/microl at 8 h) but plasma TNF was always undetectable (< 0.05
      ng/ml). Conversely, intravenous injection of 3 or 10 microg LPS 2 h prior to
      intracisternal LPS injection impaired pleocytosis (peak < 220 cells/microl) and
      delayed ( approximately 4 h) and reduced peak CSF TNF levels (3 microg LPS 5.0 +/
      1.2 ng/ml; 10 microg LPS 6.9 +/- 1.9; P < 0.05). Intravenous administration of 1
      microg LPS was less inhibitory to CSF inflammation, but delayed onset (peak 1100
      +/- 60 leucocytes/microl CSF at 8 h; 6.3 +/- 0.3 ng TNF/ml CSF at 4 h; both P <
      0.05). Neutropenia nadirs were dependent on LPS dose (1 microg, 4500 +/- 1700; 3
      microg, 1900 +/- 60; 10 microg, 1100 +/- 100 all at 4 h post-intravenous dose).
      Peak plasma TNF levels were not dose-dependent (> 8 ng/ml), but plasma TNF was
      always detectable (> 0.2 ng/ml at 10 h post-intravenous dose). Intravenous LPS
      administration at 0 h also blocked pleocytosis, but the inhibitory effect was
      lost when administration at -8 h. In conclusion, the degree and duration of
      endotoxaemia affect the meningeal inflammatory response to LPS in experimental
      meningitis.

PMID- 17177971
TI  - Spreading of antibody reactivity to non-thyroid antigens during experimental
      immunization with human thyroglobulin.
AB  - Intermolecular spreading of antibody reactivity has been implicated in the
      evolution of autoimmune disease. In this study, spreading of antibody reactivity
      to non-thyroid autoantigens after experimental immunization with thyroglobulin
      (Tg) was investigated. For this purpose, two rabbits were injected with human Tg
      six times (stages 1-6) every 3 weeks. Animals were also bled before priming.
      Antisera were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity
      to several non-thyroid antigens: bovine serum albumin (BSA), native DNA (nDNA),
      human myosin, human globular (G) and filamentous (F) actin and porcine tubulin.
      Tg-immunized animals developed the following serological reactivity pattern: (a)
      high reactivity to myosin from stage 2 onward, (b) significant reactivity to F
      actin, remaining high up to stage 6, (c) reactivity to BSA with a peak at stage
      3, (d) a small increase of reactivity to G-actin at stage 3 and (e) no increase
      of reactivity to nDNA and tubulin. The study of affinity-purified anti-Tg
      antibodies and the use of competitive assays revealed that reactivity to F-actin
      was not due to cross-reaction with Tg. On the contrary, reactivity to myosin
      during the first stages of immunization was due to cross-reaction with Tg, while
      at stage 6 it became myosin-specific. Reactivity to BSA at stage 3 was also due
      to cross-reaction with Tg. We conclude that at least part of the induced anti-Tg
      antibodies may result from the expansion of B cell clones producing polyreactive
      natural autoantibodies, and polyreactivity of anti-Tg antibodies during the first
      stages of Tg-immunization may be responsible for the intermolecular spreading of
      antibody response.

PMID- 17177973
TI  - IL-9 promotes anti-Mycobacterium leprae cytotoxicity: involvement of IFNgamma.
AB  - Interleukin 9 (IL-9) is a T-cell derived factor preferentially expressed by CD4+
      Th2 cells and it has been characterized both in human and murine systems. It is a
      pleiotropic cytokine with multiple functions on cells of the lymphoid, myeloid
      and mast cell lineages, as well as on lung epithelial cells. Other activities
      described for IL-9 support its contribution to asthma and its important role in
      helminthic infections, where a Th2 response can be protective and IL-9 enhances
      resistance or is responsible for elimination of the nematode. Nevertheless, until
      recently there were no studies on its role in bacterial infections in man. We
      have demonstrated that cytokines can modulate the specific cytotoxicity
      generation in peripheral blood mononuclear cells from leprosy patients and normal
      controls. In the present report we studied the effect of IL-9 in this
      experimental model. Our results indicate that IL-9 can counteract the negative
      effect mediated by IL-4 on the generation of M. leprae-induced cytotoxic T
      lymphocytes. Moreover, it can increase this lytic activity in controls and
      enhance the stimulatory effect of IL-2 or IL-6 in cells from leprosy patients and
      controls. IL-9 is also able to revert the inhibitory effect of IL-10 and IL-13 on
      the M. leprae-induced cytotoxic activity. Although the exact mechanism of action
      of IL-9 remains to be determined, interferon gamma seems to be required for the
      effect of IL-9 in this experimental model. These data suggest that IL-9 may have
      an atypical Th2 behaviour and play a role in the modulation of the immune
      response to mycobacterial infections.

PMID- 17177972
TI  - The dual role of p55 tumour necrosis factor-alpha receptor in Actinobacillus
      actinomycetemcomitans-induced experimental periodontitis: host protection and
      tissue destruction.
AB  - Inflammatory immune reactions in response to periodontopathogens are thought to
      protect the host against infection, but may trigger periodontal destruction.
      Thus, we examined the mechanisms by which the proinflammatory cytokine tumour
      necrosis factor (TNF)-alpha modulates the outcome of Actinobacillus
      actinomycetemcomitans-induced periodontal disease in mice. Our results showed
      that TNF-alpha receptor p55-deficient mice [p55TNF-knock-out (KO)] developed a
      less severe periodontitis in response to A. actinomycetemcomitans infection,
      characterized by significantly less alveolar bone loss and inflammatory reaction.
      Real-time polymerase chain reaction (PCR) demonstrated that levels of chemokines
      (CXCL1, 3 and 10; CCL3 and 5) and their receptors (CXCR2 and 3, CCR5) were lower
      in p55TNF-KO mice, as were matrix metalloproteinase (MMP)-1, 2 and 9 and receptor
      activator of nuclear factor kB ligand (RANKL) mRNA levels. However, the absence
      of the TNF-alpha p55 results in an impairment of protective immunity to A.
      actinomycetemcomitans infection, characterized by increased bacterial load and
      higher levels of C-reactive protein during the course of disease. Such impaired
      host response may be the result of the reduced chemoattraction of lymphocytes,
      neutrophils and macrophages, and reduced inducible nitric oxide synthase
      expression (iNOS) and myeloperoxidase (MPO) production in periodontal tissues of
      p55 TNF-KO mice. Our results demonstrate the mechanisms involved determining
      periodontal disease severity by TNF-alpha receptor p55, and its role in providing
      immune protection to A. actinomycetemcomitans periodontal infection.

PMID- 17177974
TI  - Inhibition of interleukin-8 production in human endothelial cells by
      Staphylococcus aureus supernatant.
AB  - Recent reports have shown that Staphylococcus aureus infection increases the
      expression of cytokines and cell adhesion molecules in endothelial cells and
      enhances leucocyte migration, thereby resulting in bacterial elimination. In this
      study, we analysed the production of the chemokine interleukin (IL)-8 in human
      umbilical vein endothelial cells (HUVEC) infected with several S. aureus strains
      by using reverse transcription-polymerase chain reaction and enzyme-linked
      immunosorbent assay. We found that the avirulent strains (00-51 and 00-62)
      increased IL-8 production but the virulent strains (A17 and A151) decreased it at
      both the mRNA and protein levels. We considered that the inhibition of IL-8
      production depended on certain inhibitory factor(s) secreted by bacteria. This
      was because S. aureus also abolished IL-8 expression in HUVEC treated with
      cytochalasin D, and the addition of culture supernatants of strains A17 and A151
      decreased IL-8 production in HUVEC. This factor(s) in the bacterial culture
      supernatant inhibited both basal and tumour necrosis factor (TNF)-alpha-induced
      IL-8 production. In contrast, no inhibitory effect was observed on monocyte
      chemotactic protein-1 (MCP-1) production. These results indicate that S. aureus
      can down-regulate IL-8 release in endothelial cells through the secretion of
      inhibitory factor(s), and this may result in decreased neutrophil recruitment,
      thus interfering with the host immune response to bacterial infection.

PMID- 17177975
TI  - Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co
      stimulatory pathway.
AB  - The role of resveratrol and curcumin is well documented in cancer, inflammation,
      diabetes and various other diseases. However, their immunosuppressive action on T
      cells, B cells and macrophages is not well documented. In the present study, we
      have ascertained the effect of resveratrol and curcumin on T and B cells and
      macrophages. The most striking findings were that both resveratrol and curcumin
      suppressed the activity of T and B cells and macrophages, as evidenced by
      significant inhibition in proliferation, antibody production and lymphokine
      secretion. Interestingly, curcumin imparted immunosuppression by mainly down
      regulating the expression of CD28 and CD80 and up-regulating CTLA-4. Resveratrol
      also functioned by decreasing the expression of CD28 and CD80, as well as by
      augmenting the production of interleukin (IL)-10.

PMID- 17177976
TI  - Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a
      complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and
      regulates interferon-gamma gene transcription in Th1 cells.
AB  - We have found previously that Txk, a member of the Tec family tyrosine kinases,
      is involved importantly in T helper 1 (Th1) cytokine production. However, how Txk
      regulates interferon (IFN)-gamma gene transcription in human T lymphocytes was
      not fully elucidated. In this study, we identified poly(ADP-ribose) polymerase 1
      (PARP1) and elongation factor 1alpha (EF-1alpha) as Txk-associated molecules that
      bound to the Txk responsive element of the IFN-gamma gene promoter. Txk
      phosphorylated EF-1alpha and PARP1 formed a complex with them, and bound to the
      IFN-gamma gene promoter in vitro. In particular, the N terminal region containing
      the DNA binding domain of PARP1 was important for the trimolecular complex
      formation involving Txk, EF-1alpha and PARP1. Several mutant Txk which lacked
      kinase activity were unable to form the trimolecular complex. A PARP1 inhibitor,
      PJ34, suppressed IFN-gamma but not interleukin (IL)-4 production by normal
      peripheral blood lymphocytes (PBL). Multi-colour confocal analysis revealed that
      Txk and EF-1alpha located in the cytoplasm in the resting condition. Upon
      activation, a complex involving Txk, EF-1alpha and PARP1 was formed and was
      located in the nucleus. Collectively, Txk in combination with EF-1alpha and PARP1
      bound to the IFN-gamma gene promoter, and exerted transcriptional activity on the
      IFN-gamma gene.

PMID- 17177977
TI  - Innate immunity mediated by epidermal keratinocytes promotes acquired immunity
      involving Langerhans cells and T cells in the skin.
AB  - Skin is an immunological organ consisting of epidermal cells, i.e. keratinocytes
      and Langerhans cells (LCs, antigen-presenting dendritic cells), and both innate
      and acquired immune systems operate upon exposure of the skin to various external
      microbes or their elements. To explore the relationship between innate and
      acquired immunities in the skin, we investigated whether Toll-like receptor (TLR)
      ligation of epidermal cells enhances the ability of LCs to present a specific
      antigen to T cells in mice. LC-containing epidermal cells were incubated with CpG
      oligonucleotide (TLR9 ligand) modified with trinitrophenyl hapten, and cultured
      with hapten-primed CD4(+) T cells. TLR9 ligand was capable of enhancing the
      hapten-presenting ability of LCs when LC-enriched epidermal cells, but not
      purified LCs, were used as the LC source, suggesting that bystander keratinocytes
      play a role in the enhancement of LC function. Cultivation of freshly isolated
      epidermal cells with CpG promoted the expression of major histocompatibility
      complex (MHC) class II and CD86 molecules on LCs. CpG enhanced the production of
      interleukin (IL)-1alpha, granulocyte-macrophage colony-stimulating factor (GM
      CSF) and tumour necrosis factor (TNF)-alpha by primarily cultured keratinocytes.
      The addition of a cocktail of neutralizing antibodies against these cytokines
      abrogated the CpG-promoted, antigen-presenting ability of LC-enriched epidermal
      cells. Moreover, the addition of culture supernatants from CpG-stimulated
      keratinocytes restored the ability of purified LCs. Our study demonstrated that
      although the direct effect of CpG on LCs is minimal, LC function can be up
      regulated indirectly by cytokines released by CpG-stimulated keratinocytes. This
      also implies that innate immunity evoked by TLR ligation of keratinocytes
      enhances acquired immunity comprising LCs and T cells.

PMID- 17177978
TI  - Altered immune function of monocytes in different stages of patients with acute
      on chronic liver failure.
AB  - The aim of this study was to investigate the characteristics of the immune
      function of monocytes in different stages of the patients with acute on chronic
      liver failure (ACLF). Human leucocyte antigen (HLA)-DR and Toll-like receptor 4
      (TLR-4) expression on monocytes in early and late stages of acute on chronic
      liver failure were detected by flow cytometry. The secretion function of
      monocytes was measured by cytometric bead array. Compared with healthy controls,
      the levels of HLA-DR expression on monocytes in patients with chronic hepatitis
      B, liver cirrhosis and acute on chronic liver failure were gradually decreased,
      especially in the late stage of acute on chronic liver failure (P < 0.001). TLR-4
      expression on monocytes in patients with liver cirrhosis and acute on chronic
      liver failure were higher than the healthy controls. The concentrations of
      interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha and IL-12p70 in early
      stage ACLF were significantly higher compared with healthy controls and lower in
      late-stage ACLF (P < 0.01, 0.05). However, a significantly lower amount of IL-10
      was found on monocytes in early-stage ACLF than that of late-stage ACLF and
      healthy controls (P < 0.01). Monocyte HLA-DR expression in patients who died was
      significantly lower compared with patients who survived in the early and late
      stages of ACLF (P < 0.01). The dynamic detection of HLA-DR expression or
      cytokines secreted from monocytes could contribute to the estimation of the
      status of the immune function of patients with acute on chronic liver failure.

PMID- 17177981
TI  - Following damage, the majority of bone marrow-derived airway cells express an
      epithelial marker.
AB  - BACKGROUND: Adult-derived bone marrow stem cells are capable of reconstituting
      the haematopoietic system. However there is ongoing debate in the literature as
      to whether bone marrow derived cells have the ability to populate other tissues
      and express tissue specific markers. The airway has been an organ of major
      interest and was one of the first where this was demonstrated. We have previously
      demonstrated that the mouse airway can be repopulated by side population bone
      marrow transplanted cells. Here we investigate the frequency and phenotypic
      nature of these bone marrow derived cells. METHODS: Female mice were engrafted
      with male whole bone marrow or side population (SP) cells and subjected to
      detergent-induced damage after 3 months. Donor cells were identified by Y
      chromosome fluorescence in situ hybridisation and their phenotype was assessed by
      immunohistochemistry on the same sections. Slides were visualised by a
      combination of widefield and deconvolved microscopy and whole cells were analysed
      on cytospin preparations. RESULTS: The frequencies of engraftment of male cells
      in the airway of mice that show this (9/10), range from 1.0-1.6% with whole
      marrow and 0.6-1.5% with SP cells. Undamaged controls have only between 0.1 and
      0.2% male cells in the trachea. By widefield microscopy analysis we find 60.2%
      (53/88) of male donor derived cells express cytokeratins as a marker of
      epithelial cells. These results were reinforced using deconvolved microscopy and
      scored by two independent investigators. In addition cytospin analysis of cells
      dissociated from the damaged trachea of engrafted mice also reveals donor derived
      Y chromosome positive cells that are immunopositive for cytokeratin. Using
      cytokeratin and the universal haematopoietic marker CD45 immunohistochemistry, we
      find the donor derived cells fall into four phenotypic classes. We do not detect
      cytokeratin positive cells in whole bone marrow using cytokeratin immunostaining
      and we do not detect any cytokeratin mRNA in SP or bone marrow samples by RT-PCR.
      CONCLUSION: The appearance of bone marrow derived cells in the tracheal
      epithelium is enriched by detergent-induced tissue damage and the majority of
      these cells express an epithelial marker. The cytokeratin positive donor derived
      cells in the tracheal epithelium are not present in the injected donor cells and
      must have acquired this novel phenotype in vivo.

PMID- 17177982
TI  - Induced hypertension for the treatment of acute MCA occlusion beyond the
      thrombolysis window: case report.
AB  - BACKGROUND: A minority of stroke patients is eligible for thrombolytic therapy.
      Small pilot case series have hinted that elevation of incident arterial blood
      pressure might be associated with a favorable prognosis either in acute or
      subacute stroke. However, these patients were not considered for thrombolytic
      therapy and were not followed - up systematically. We used pharmacologically
      induced hypertension in a stroke patient with middle cerebral artery (MCA)
      occlusion ineligible for thrombolysis that was followed-up by radiological,
      clinical and functional outcome assessment. CASE PRESENTATION: A patient with
      acute embolic MCA occlusion producing a large, ischemic penumbra confirmed by
      perfusion CT was treated by induced hypertension with phenylephrine started
      within 4 h of admission. Increase in the mean arterial pressure by 20% led to a
      reduction of neurological deficit by 3 points on the National Institute of Stroke
      Scale. MRI and CT scans performed during phenylephrine infusion showed the
      presence of limited subcortical and cortical infarct changes that were clearly
      less extensive than the perfusion deficit in the brain perfusion CT at baseline,
      found in the absence of MCA patency. No complications due to induced hypertension
      therapy occurred. Moderate functional improvement up to modified Rankin scale 2
      at follow up took place. CONCLUSION: Induced hypertension in acute ischemic
      stroke seems clinically feasible and may be beneficial in selected normo- or
      hypotensive stroke patients not eligible for thrombolytic recanalization therapy.

PMID- 17177979
TI  - Induction of interleukins IL-6 and IL-8 by siRNA.
AB  - The HIV-1 co-receptor CCR5 has been thought a relevant target for small
      interfering RNA (siRNA)-based therapeutics. However, recent findings suggest that
      siRNA can stimulate innate cytokine responses in mammals. All siRNA agents tested
      were able to down-regulate the expression of CCR5, albeit with different
      efficiency (51-74% down-regulation), block HIV-induced syncytia formation between
      HIV-1 BaL-infected and uninfected CD4(+) cells or block single-round HIV-1
      infection as measured by a luciferase reporter assay (46-83% inhibition).
      Conversely, siRNA directed against CCR5 did not affect replication of a vesicular
      stomatitis virus (VSV) pseudotyped virus, suggesting that inhibition of HIV
      replication was specific to CCR5 down-regulation. However, two of four siRNA
      tested were able to induce the production of interleukin (IL) IL-6 (sixfold
      induction) and IL-8 (ninefold induction) but no interferon (IFN)-alpha, IFN-beta,
      IFN-gamma, tumour necrosis factor (TNF)-alpha, monocyte chemoattractant protein
      (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, IL
      1beta, IL-10 or IL-12p70 cytokine induction was noted. In the absence of
      detectable IFN-alpha, IL-6 or IL-8 may represent markers of non-specific effects
      triggered by siRNA.

PMID- 17177983
TI  - Fracture risk and the use of a diuretic (indapamide SR) +/- perindopril: a
      substudy of the Hypertension in the Very Elderly Trial (HYVET).
AB  - BACKGROUND: The Hypertension in the Very Elderly Trial (HYVET) is a placebo
      controlled double blind trial of treating hypertension with indapamide Slow
      Release (SR) +/- perindopril in subjects over the age of 80 years. The primary
      endpoints are stroke (fatal and non fatal). In view of the fact that thiazide
      diuretics and indapamide reduce urinary calcium and may increase bone mineral
      density, a fracture sub study was designed to investigate whether or not the
      trial anti-hypertensive treatment will reduce the fracture rate in very elderly
      hypertensive subjects. METHODS: In the trial considerable care is taken to
      ascertain any fractures and to identify risk factors for fracture, such as falls,
      co-morbidity, drug treatment, smoking and drinking habits, levels of activity,
      biochemical abnormalities, cardiac irregularities, impaired cognitive function
      and symptoms of orthostatic hypotension. POTENTIAL RESULTS: The trial is expected
      to provide 10,500 patient years of follow-up. Given a fracture rate of 40/1000
      patient years and a 20% difference in fracture rate, the power of the sub study
      is 58% to detect this difference at the 5% level of significance. The
      corresponding power for a reduction of 25% is 78%. CONCLUSION: The trial is well
      under way, expected to complete in 2009, and on target to detect, if present, the
      above differences in fracture rate.

PMID- 17177984
TI  - Effect of iron on the expression of sirR and sitABC in biofilm-associated
      Staphylococcus epidermidis.
AB  - BACKGROUND: Different gene expression patterns correlate with the altered
      phenotype in biofilm-associated bacteria. Iron and iron-linked genes are thought
      to play a key-role in biofilm formation. The expression of Fe-linked genes (sirR,
      sitABC operon) in Staphylococcus epidermidis, was compared in planktonic versus
      sessile bacteria in vitro and in vivo in a subcutaneous foreign body rat model.
      RESULTS: In vitro in a Fe-limited environment, the planktonic form of S.
      epidermidis produces siderophores and grows slower than in Fe-rich environment.
      The expression of sirR in planktonic bacteria, in vitro, was not different in
      medium without Fe or with 1 microM FeCl3. High Fe concentrations (25 microM
      FeCl3) increased expression of sirR transiently during the early phase of
      incubation. Expression of sitC in vitro, in planktonic bacteria, was inversely
      correlated with sirR expression in medium with 25 microM FeCl3: sitC expression
      decreased for the first 3 hours followed by an up regulation.In sessile bacteria
      in vitro, sirR expression was high and independent of the Fe concentration. The
      expression of sitC was not inversely correlated to sirR expression. In vivo,
      expression levels of sirR and of sitABC were high during the initial phase after
      implantation and, after a transient decrease, remained stable over a period of
      two weeks. CONCLUSION: Our data suggest that the expression of sirR and the
      regulatory effect of sirR on the sitABC operon are different in planktonic and
      sessile bacteria.

PMID- 17177985
TI  - The high frequency of manic symptoms in fibromyalgia does influence the choice of
      treatment?
AB  - BACKGROUND: Mood disorders were found associated with fibromyalgia (FM) and
      clinical studies have revealed the efficacy of antidepressant drugs in the
      treatment of FM. However no specific instruments to identify manic symptoms were
      used. OBJECTIVES: To assess the frequency of anxiety and mood disorders
      (particularly bipolar disorders and manic symptoms) in a consecutive sample of
      women affected by FM using standardized diagnostic tools and to compare the
      prevalence of these disorders with that observed in a sample of healthy controls
      from the general population. METHODS:  CASES: consecutive series of women (N =
      37, mean age 50.1 +/- 21.0) attending a Rheumatology outpatient Unit at the
      University of Cagliari. CONTROLS: 148 women, drawn from the data bank of an
      epidemiological study matched for sex and age with controls according to a
      randomisation "after blocks" method. The Italian version of the Composite
      International Diagnostic Interview Simplified were carried out by physicians.
      Psychiatric diagnosis was formulated according to DSM-IV criteria. The Italian
      version of the Mood Disorder Questionnaire (MDQ) was administered to identify
      manic symptoms and bipolar disorders. Diagnosis of FM were carried out by
      rheumatologist according to the criteria of American College of Rheumatology.
      RESULTS: Subjects with FM showed a higher comorbidity with Generalised Anxiety
      Disorder, Panic Disorder and Major Depressive Disorder than controls. The study
      showed a high frequency of manic symptoms (MDQ positive) in the sample of
      fibromyalgic patients (59%), approximately double that found in the control
      sample (P < 0.001). DISCUSSION: Clinical studies have shown the efficacy of
      antidepressants, especially tricyclic antidepressants, in the treatment of FM.
      The clinical difficulty in identifying hypomanic episodes is well known
      particularly where previous and not present episodes are concerned as in
      depressive patients. These data would suggest further studies on the subject are
      needed and more caution also in prescribing antidepressants in a population
      apparently at high risk for bipolar disorders.

PMID- 17177987
TI  - Role of pyrite in formation of hydroxyl radicals in coal: possible implications
      for human health.
AB  - BACKGROUND: The harmful effects from inhalation of coal dust are well-documented.
      The prevalence of lung disease varies by mining region and may, in part, be
      related to regional differences in the bioavailable iron content of the coal.
      Pyrite (FeS2), a common inorganic component in coal, has been shown to
      spontaneously form reactive oxygen species (ROS) (i.e., hydrogen peroxide and
      hydroxyl radicals) and degrade nucleic acids. This raises the question regarding
      the potential for similar reactivity from coal that contains pyrite. Experiments
      were performed to specifically evaluate the role of pyrite in coal dust
      reactivity. Coal samples containing various amounts of FeS2 were compared for
      differences in their generation of ROS and degradation of RNA. RESULTS: Coals
      that contain iron also show the presence of FeS2, generate ROS and degrade RNA.
      Coal samples that do not contain pyrite do not produce ROS nor degrade RNA. The
      concentration of generated ROS and degradation rate of RNA both increase with
      greater FeS2 content in the coals. CONCLUSION: The prevalence of coal workers'
      pneumoconiosis can be correlated to the amount of FeS2 in the coals. Considering
      the harmful effects of generation of ROS by inhaled particles, the results
      presented here show a possible mechanism whereby coal samples may contribute to
      CWP. This suggests that the toxicity of coal may be explained, in part, by the
      presence of FeS2.

PMID- 17177988
TI  - Analytical and preparative applications of magnetic split-flow thin fractionation
      on several ion-labeled red blood cells.
AB  - BACKGROUND: Magnetic Split-flow thin (SPLITT) fractionation is a newly developed
      technique for separating magnetically susceptible particles. Particles with
      different field-induced velocities can be separated into two fractions by
      adjusting applied magnetic forces and flow-rates at inlets and outlets. METHODS:
      Magnetic particles, Dynabeads, were used to test this new approach of field
      induced velocity for susceptibility determination using magnetic SF at different
      magnetic field intensities. Reference measurements of magnetic susceptibility
      were made using a superconducting quantum interference device (SQUID)
      magnetometer. Various ion-labeled red blood cells (RBC) were used to study
      susceptibility determination and throughput parameters for analytical and
      preparative applications of magnetic SPLITT fractionation (SF), respectively.
      Throughputs were studied at different sample concentrations, magnetic field
      intensities, and channel flow-rates. RESULTS: The susceptibilities of Dynabeads
      determined by SPLITT fractionation (SF) were consistent with those of reference
      measurement using a superconducting quantum interference device (SQUID)
      magnetometer. Determined susceptibilities of ion-labeled RBC were consistent
      within 9.6% variations at two magnetic intensities and different flow-rates. The
      determined susceptibilities differed by 10% from referenced measurements. The
      minimum difference in magnetic susceptibility required for complete separation
      was about 5.0 x 10(-6) [cgs]. Sample recoveries were higher than 92%. The
      throughput of magnetic SF was approximately 1.8 g/h using our experimental setup.
      CONCLUSION: Magnetic SF can provide simple and economical determination of
      particle susceptibility. This technique also has great potential for cell
      separation and related analysis. Continuous separations of ion-labeled RBC using
      magnetic SF were successful over 4 hours. The throughput was increased by 18
      folds versus early study. Sample recoveries were 93.1 +/- 1.8% in triplicate
      experiments.

PMID- 17177986
TI  - Cell cycle regulation by the Wee1 inhibitor PD0166285, pyrido [2,3-d] pyimidine,
      in the B16 mouse melanoma cell line.
AB  - BACKGROUND: Wee1 kinase plays a critical role in maintaining G2 arrest through
      its inhibitory phosphorylation of cdc2. In previous reports, a pyridopyrimidine
      molecule PD0166285 was identified to inhibit Wee1 activity at nanomolar
      concentrations. This G2 checkpoint abrogation by PD0166285 was demonstrated to
      kill cancer cells, there at a toxic highest dose of 0.5 muM in some cell lines
      for exposure periods of no longer than 6 hours. The deregulated cell cycle
      progression may have ultimately damaged the cancer cells. We herein report one of
      the mechanism by which PD0166285 leads to cell death in the B16 mouse melanoma
      cell line. METHODS: Tumor cell proliferation was determined by counting cell
      numbers. Cell cycle distribution was determined by flow cytometry. Morphogenesis
      analysis such as microtubule stabilization, Wee1 distribution, and cyclin B
      location were observed by immunofluorescence confocal microscopy. An immunoblot
      analysis of cdc2-Tyr15, cyclin D, E, p16, 21, 27, and Rb. A real-time PCR of the
      mRNA of cyclin D were completed. RESULTS: In our experiment, B16 cells also
      dramatically abrogated the G2 checkpoint and were found to arrest in the early G1
      phase by treatment with 0.5 muM for 4 hours observed by flow cytometry. Cyclin D
      mRNA decreased within 4 hours observed by Real-time PCR. Rb was dephosphrylated
      for 24 hours. However, B16 cells did not undergo cell death after 0.5 muM
      treatment for 24 hours. Immnofluoscence microscopy showed that the cells become
      round and small in the morphogenesis. More interesting phenomena were that
      microtubule stabilization was blocked, and Wee1 distribution was restricted after
      treatment for 4 hours. CONCLUSION: We analyzed the effect of Wee1 inhibitor
      PD0166285 described first by Wang in the G2 transition in the B16 melanoma cell
      line. The inhibitor PD0166285 abrogated G2/M checkpoint inducing early cell
      division. Moreover, we found that the treatment of cells with the inhibitor is
      related to microtubule stabilization and decrease in cyclin D transcription.
      These effects together suggest that Wee1 inhibitor may thus be a potentially
      useful anti-cancer therapy.

PMID- 17177989
TI  - Prognostic significance of multidrug-resistance protein (MDR-1) in renal clear
      cell carcinomas: a five year follow-up analysis.
AB  - BACKGROUND: A large number of renal cancer patients shows poor or partial
      response to chemotherapy and the mechanisms have not been still understood. Multi
      drug resistance is the principal mechanism by which many cancers develop
      resistance to chemotherapic drugs. The role of the multi-drug resistant
      transporter (MDR-1/P-glycoprotein), the gene product of MDR-1, and that one of
      the so-called multi-drug resistance associated protein (MRP), two energy
      dependent efflux pumps, are commonly known to confer drug resistance. We studied
      MDR-1 expression in selected cases of renal cell carcinoma (RCC), clear cell
      type, with long-term follow-up, in order to establish its prognostic role and its
      possible contribution in the choice of post-surgical therapy. METHODS: MDR-1 has
      been studied by standard LSAB-HRP immunohistochemical technique, in paraffin
      embedded RCC samples. Protein expression has been compared to clinical and
      histopathological data and to disease specific survival of RCC patients, by
      Kaplan-Meier curve and Cox multivariate regression analyses. RESULTS: Two groups
      of RCCs were obtained by esteeming MDR-1 expression and disease specific survival
      (obtained with Kaplan-Meier curve and Cox multivariate regression analyses): the
      first one presents low or absent MDR-1 expression and good survival; the second
      one is characterized by high MDR-1 expression and significant poor outcome (p <
      0.05). Afterwards, we have found disease specific survival, adjusted for stages
      and independent of therapy: this difference of survival rates was statistically
      significant (p < 0.05). Stage adjusted disease specific survival rate, according
      to MDR-1 expression and therapy in patients affected by RCC in early stage (stage
      I), has revealed that the group of patients with high MDR-1 expression and
      without adjuvant therapy showed poor survival (p < 0.05). Cox multivariate
      regression analysis has confirmed that, in our cohort of RCC (clear cell type)
      patients, the strong association between MDR-1 and worse outcome is independent
      not only of the adjuvant therapy, but also of the other prognostic parameters (p
      < 0.05). CONCLUSION: In our opinion, the results of this study well prove the
      relationship between MDR-1 expression and worse clinical prognosis in RCC,
      because MDR-1 over-expressing RCCs can be considered a group of tumours with a
      more aggressive behavior. This finding outlines a possible role of MDR-1 as
      prognostic factor, dependent and independent of multidrug resistance. These
      results could be useful to predict cancer evolution and to choose the appropriate
      treatment: this is another step that can stimulate further promising and
      interesting investigations on broader study population.

PMID- 17177990
TI  - Dialkyl phosphate metabolites of organophosphorus in applicators of agricultural
      pesticides in Majes - Arequipa (Peru).
AB  - BACKGROUND: Organophosphorus (OPs) pesticides are the most commonly used
      pesticides in Peruvian agriculture. The population at risk for OPs exposure
      includes formulators, applicators and farmers. Majes Valley is the most important
      agricultural center of the Southern region of Peru. The present study was aimed
      to determine the knowledge about using OPs, safety practice and urinary
      dialkylphosphate metabolites on OP applicators in the Majes Valley, Peru.
      METHODS: This study was based on a questionnaire which included socio-demographic
      characteristics, knowledge of safety practices to handling OPs, characteristics
      of pesticide application and use of protective measures to avoid pesticide
      contamination. Exposure was assessed by measuring six urinary OP metabolites
      (DMP, DMTP, DMDTP, DEP, DETP, and DEDTP) by gas chromatography using a single
      flame photometric detector. The sample consisted of 31 men and 2 women aged 20 -
      65 years old. RESULTS: 76% of applicators had at least one urinary
      dialkylphosphate metabolite above the limit of detection. The geometric mean (GM)
      and the geometric standard deviation (GSD) of DMP and DEP were 5.73 microg/g cr.
      (GSD 2.51), and 6.08 microg/g cr. (GSD 3.63), respectively. The percentage of
      applicators with detectable DMP, DMDTP, and DMTP in urine was 72.72%, 3.03%, and
      15.15%, respectively, while the corresponding figures for DEP, DETP, and DEDTP
      were 48.48%, 36.36% and 15.15%, respectively. There was no significant
      association between the use of protection practices and the absence of urine OPs
      metabolites suggesting inadequate protection practices. CONCLUSION: The pesticide
      applicators in Majes Valley have significant exposure to OP pesticides, probably
      due to inappropriate protective practices. Future work should evaluate possible
      health effects.

PMID- 17177991
TI  - Clinical presentation and predictors of outcome in patients with severe acute
      exacerbation of chronic obstructive pulmonary disease requiring admission to
      intensive care unit.
AB  - BACKGROUND: Severe acute exacerbation of chronic obstructive pulmonary disease
      (AE-COPD) is a common reason for emergency room (ER) visit about which little has
      been documented from India. METHODS: Prospective study of the clinical
      presentation and predictors of outcome in 116 patients presenting with severe AE
      COPD requiring admission to the medical intensive care unit between January 2000
      and December 2004. RESULTS: Their mean age was 62.1 +/- 9.8 years. There were 102
      males. Mean duration of COPD was 7.2 +/- 5.8 years. All males were smokers (22.3
      +/- 11.2 pack years); 35.2% smoked cigarettes and 64.8% smoked bidis. All women
      were exposed to domestic fuel. Associated co-morbid illnesses were present in 81
      patients (69.8%); 53(45.7%) had one co-morbid illness and the remaining 28
      (54.3%) had two or more co-morbid illnesses. Evidence of past pulmonary
      tuberculosis (PTB) was present in 28.4% patients; 5 patients who also had type II
      diabetes mellitus had active PTB. Arterial blood gas analysis revealed
      respiratory failure in 40 (33.8%) patients (type I 17.5% and type II 82.5%).
      Invasive mechanical ventilation was required in 18 patients. Sixteen (13.7%)
      patients died. Stepwise multivariate logistic regression analysis revealed need
      for invasive ventilation (OR 45.809, 95% CI 607.46 to 3.009;p < 0.001); presence
      of co-morbid illness (OR 0.126, 95% CI 0.428 to 0.037;p < 0.01) and hypercapnia
      (OR 0.114, 95% CI 1.324 to 0.010;p < 0.05) were predictors of death. CONCLUSION:
      Co-morbid conditions and metabolic abnormalities render the diagnosis of AE-COPD
      difficult and also contribute to mortality. High prevalence of past PTB and
      active PTB in patients with AE-COPD suggests an intriguing relationship between
      smoking, PTB and COPD which merits further study.

PMID- 17177992
TI  - Case-Control study of Firefighters with documented positive tuberculin skin test
      results using Quantiferon-TB testing in comparison with Firefighters with
      negative tuberculin skin test results.
AB  - BACKGROUND: Phoenix Firefighters have had abnormally high rates of tuberculin
      skin test (TBST) results on medical surveillance. The objectives of this study
      were to evaluate our firefighters using QuantiFERON-TB (QFT), comparing the
      results to their TBST results. METHODS: Using QFT results obtained during the
      study, we compared previously positive TBST responders (Cases) to negative
      responders (Controls). We also compared both groups for QFT results for
      Mycobacterium avium (MA) exposure. RESULTS: QFT effectively monitored our working
      population. 12.9% of the 148 cases, and 3.2% of the 220 controls had a positive
      QFT result. Another 14.8% of cases and 4.5% of controls had conditionally
      positive QFT results. There was an unusually high rate of MA response on QFT
      testing in both groups. CONCLUSION: Phoenix Firefighters have a higher than
      expected TBST and QFT results, which cannot be explained by the increased MA
      rate. The decreased level of QFT positivity in comparison to TBST results may
      indicate a considerable false positive TBST rate. The QFT offers many advantages
      as a surveillance method over TBST in exposed worker populations.

PMID- 17177993
TI  - IMP PCR primers detect single nucleotide polymorphisms for Anopheles gambiae
      species identification, Mopti and Savanna rDNA types, and resistance to dieldrin
      in Anopheles arabiensis.
AB  - BACKGROUND: Polymerase chain reactions to distinguish single-nucleotide
      polymorphisms are commonly used for mosquito identification and identifying
      insecticide resistance alleles. However, the existing methods used for primer
      design often result in analyses that are not robust or require additional steps.
      METHODS: Utilizing oligonucleotides that are unique in having an intentional
      mismatch to both templates three bases from the SNP at the 3-prime end, three new
      PCR assays that distinguish SNP targets using standard gel electrophoresis of
      undigested DNA fragments were developed and tested. These were applied to: (1) an
      alternative ribosomal DNA PCR assay to distinguish five members of the Anopheles
      gambiae complex; (2) detection of the Mopti and Savanna rDNA types; and (3) an
      assay to distinguish resistance to dieldrin (Rdl) alleles in Anopheles
      arabiensis. RESULTS: Reproducible specific amplification of the target alleles
      was observed in all three assays. The results were consistent with existing
      analyses but proved simpler and the results more distinct in our hands.
      CONCLUSION: The simplicity and effectiveness of the method should be utilized in
      these and other PCR analyses to increase their specificity and simplicity. These
      results have the potential to be extended not only to mosquito analyses but also
      to parasite and human polymorphisms.

PMID- 17177994
TI  - The role of synovial macrophages and macrophage-produced cytokines in driving
      aggrecanases, matrix metalloproteinases, and other destructive and inflammatory
      responses in osteoarthritis.
AB  - There is an increasing body of evidence that synovitis plays a role in the
      progression of osteoarthritis and that overproduction of cytokines and growth
      factors from the inflamed synovium can influence the production of degradative
      enzymes and the destruction of cartilage. In this study, we investigate the role
      of synovial macrophages and their main proinflammatory cytokines, interleukin
      (IL)-1 and tumour necrosis factor-alpha (TNF-alpha), in driving osteoarthritis
      synovitis and influencing the production of other pro- and anti-inflammatory
      cytokines, production of matrix metalloproteinases, and expression of
      aggrecanases in the osteoarthritis synovium. We established a model of cultures
      of synovial cells from digested osteoarthritis synovium derived from patients
      undergoing knee or hip arthroplasties. By means of anti-CD14-conjugated magnetic
      beads, specific depletion of osteoarthritis synovial macrophages from these
      cultures could be achieved. The CD14+-depleted cultures no longer produced
      significant amounts of macrophage-derived cytokines like IL-1 and TNF-alpha.
      Interestingly, there was also significant downregulation of several cytokines,
      such as IL-6 and IL-8 (p < 0.001) and matrix metalloproteinases 1 and 3 (p <
      0.01), produced chiefly by synovial fibroblasts. To investigate the mechanisms
      involved, we went on to use specific downregulation of IL-1 and/or TNF-alpha in
      these osteoarthritis cultures of synovial cells. The results indicated that
      neutralisation of both IL-1 and TNF-alpha was needed to achieve a degree of
      cytokine (IL-6, IL-8, and monocyte chemoattractant protein-1) and matrix
      metalloproteinase (1, 3, 9, and 13) inhibition, as assessed by enzyme-linked
      immunosorbent assay and by reverse transcription-polymerase chain reaction (RT
      PCR), similar to that observed in CD14+-depleted cultures. Another interesting
      observation was that in these osteoarthritis cultures of synovial cells, IL-1beta
      production was independent of TNF-alpha, in contrast to the situation in
      rheumatoid arthritis. Using RT-PCR, we also demonstrated that whereas the ADAMTS4
      (a disintegrin and metalloprotease with thrombospondin motifs 4) aggrecanase was
      driven mainly by TNF-alpha, ADAMTS5 was not affected by neutralisation of IL-1
      and/or TNF-alpha. These results suggest that, in the osteoarthritis synovium,
      both inflammatory and destructive responses are dependent largely on macrophages
      and that these effects are cytokine-driven through a combination of IL-1 and TNF
      alpha.

PMID- 17177995
TI  - Intensity-based hierarchical Bayes method improves testing for differentially
      expressed genes in microarray experiments.
AB  - BACKGROUND: The small sample sizes often used for microarray experiments result
      in poor estimates of variance if each gene is considered independently. Yet
      accurately estimating variability of gene expression measurements in microarray
      experiments is essential for correctly identifying differentially expressed
      genes. Several recently developed methods for testing differential expression of
      genes utilize hierarchical Bayesian models to "pool" information from multiple
      genes. We have developed a statistical testing procedure that further improves
      upon current methods by incorporating the well-documented relationship between
      the absolute gene expression level and the variance of gene expression
      measurements into the general empirical Bayes framework. RESULTS: We present a
      novel Bayesian moderated-T, which we show to perform favorably in simulations,
      with two real, dual-channel microarray experiments and in two controlled single
      channel experiments. In simulations, the new method achieved greater power while
      correctly estimating the true proportion of false positives, and in the analysis
      of two publicly-available "spike-in" experiments, the new method performed
      favorably compared to all tested alternatives. We also applied our method to two
      experimental datasets and discuss the additional biological insights as revealed
      by our method in contrast to the others. The R-source code for implementing our
      algorithm is freely available at http://eh3.uc.edu/ibmt. CONCLUSION: We use a
      Bayesian hierarchical normal model to define a novel Intensity-Based Moderated T
      statistic (IBMT). The method is completely data-dependent using empirical Bayes
      philosophy to estimate hyperparameters, and thus does not require specification
      of any free parameters. IBMT has the strength of balancing two important factors
      in the analysis of microarray data: the degree of independence of variances
      relative to the degree of identity (i.e. t-tests vs. equal variance assumption),
      and the relationship between variance and signal intensity. When this variance
      intensity relationship is weak or does not exist, IBMT reduces to a previously
      described moderated t-statistic. Furthermore, our method may be directly applied
      to any array platform and experimental design. Together, these properties show
      IBMT to be a valuable option in the analysis of virtually any microarray
      experiment.

PMID- 17177996
TI  - Lung cancer induced in mice by the envelope protein of jaagsiekte sheep
      retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV.
AB  - BACKGROUND: Jaagsiekte sheep retrovirus (JSRV) causes a lethal lung cancer in
      sheep and goats. Expression of the JSRV envelope (Env) protein in mouse lung, by
      using a replication-defective adeno-associated virus type 6 (AAV6) vector,
      induces tumors resembling those seen in sheep. However, the mouse and sheep
      tumors have not been carefully compared to determine if Env expression alone in
      mice can account for the disease features observed in sheep, or whether
      additional aspects of virus replication in sheep are important, such as oncogene
      activation following retrovirus integration into the host cell genome. RESULTS:
      We have generated mouse monoclonal antibodies (Mab) against JSRV Env and have
      used these to study mouse and sheep lung tumor histology. These Mab detect Env
      expression in tumors in sheep infected with JSRV from around the world with high
      sensitivity and specificity. Mouse and sheep tumors consisted mainly of well
      differentiated adenomatous foci with little histological evidence of anaplasia,
      but at long times after vector exposure some mouse tumors did have a more
      malignant appearance typical of adenocarcinoma. In addition to epithelial cell
      tumors, lungs of three of 29 sheep examined contained fibroblastic cell masses
      that expressed Env and appeared to be separate neoplasms. The Mab also stained
      nasal adenocarcinoma tissue from one United States sheep, which we show was due
      to expression of Env from ovine enzootic nasal tumor virus (ENTV), a virus
      closely related to JSRV. Systemic administration of the AAV6 vector encoding JSRV
      Env to mice produced numerous hepatocellular tumors, and some hemangiomas and
      hemangiosarcomas, showing that the Env protein can induce tumors in multiple cell
      types. CONCLUSION: Lung cancers induced by JSRV infection in sheep and by JSRV
      Env expression in mice have similar histologic features and are primarily
      characterized by adenomatous proliferation of peripheral lung epithelial cells.
      Thus it is unnecessary to invoke a role for insertional mutagenesis, gene
      activation, viral replication, or expression of other viral gene products in
      sheep lung tumorigenesis, although these processes may play a role in other
      clinically less important sequelae of JSRV infection such as metastasis observed
      with variable frequency in sheep.

PMID- 17177997
TI  - Molecular monitoring of Plasmodium falciparum resistance to artemisinin in
      Tanzania.
AB  - Artemisinin-based combination therapies (ACTs) are recommended for use against
      uncomplicated malaria in areas of multi-drug resistant malaria, such as sub
      Saharan Africa. However, their long-term usefulness in these high transmission
      areas remains unclear. It has been suggested that documentation of the S769N
      PfATPase6 mutations may indicate an emergence of artemisinin resistance of
      Plasmodium falciparum in the field. The present study assessed PfATPase6
      mutations (S769N and A623E) in 615 asymptomatic P. falciparum infections in
      Tanzania but no mutant genotype was detected. This observation suggests that
      resistance to artemisinin has not yet been selected in Tanzania, supporting the
      Ministry of Health's decision to adopt artemether+lumefantrine as first-line
      malaria treatment. The findings recommend further studies to assess PfATPase6
      mutations in sentinel sites and verify their usefulness in monitoring emergency
      of ACT resistance.

PMID- 17177998
TI  - Sex differences in inflammatory cytokine production in hepatic ischemia
      reperfusion.
AB  - BACKGROUND: The inflammatory response to hepatic ischemia-reperfusion (I/R) is
      associated with an increase in cytokine production. Studies have documented that
      sex hormones modulate both the innate and adaptive immune responses, and that
      females are more robust than males. The aim of this study was to determine
      whether a sex difference in cytokine response to hepatic I/R exists under normal
      pathophysiologic condition without hormone intervention. METHODS: Adult C57BL/6
      mice underwent 90 min of hepatic ischemia followed by various reperfusion periods
      (0, 1.5, 3, 6 hr). Plasma cytokine TNF-alpha, IL-6, MIP-2, and KC were measured.
      Liver injury was assessed by plasma alanine transaminase (ALT) levels and liver
      histopathology. RESULTS: A reperfusion time-dependent increase in hepatocellular
      injury was observed in both males and females, as indicated by increasing levels
      of plasma ALT and liver histopathology. The plasma cytokines were significantly
      increased in both female and male I/R groups compared to their respective sham
      counterparts. However, there was a significant difference in cytokine kinetics
      between the female and male I/R groups. Female mice initially had a higher level
      of IL-6, KC, and MIP-2 in response to I/R, which began to decline after 3 hr of
      reperfusion and were significantly lower than the male I/R counterparts by 6 hr
      of reperfusion. In contrast, the hepatocellular injury and TNF production were
      only moderately lower in female IR than male IR. CONCLUSION: The study
      underscores role of the gender in differential inflammatory cytokine expression
      in response to hepatic I/R, which may reflect the host response outcome.

PMID- 17177999
TI  - Mast cells dysregulate apoptotic and cell cycle genes in mucosal squamous cell
      carcinoma.
AB  - BACKGROUND: Mucosal squamous cell carcinoma of the head and neck is a disease of
      high mortality and morbidity. Interactions between the squamous cell carcinoma
      and the host's local immunity, and how the latter contributes to the biological
      behavior of the tumor are unclear. In vivo studies have demonstrated sequential
      mast cell infiltration and degranulation during squamous cell carcinogenesis. The
      degree of mast cell activation correlates closely with distinct phases of
      hyperkeratosis, dysplasia, carcinoma in-situ and invasive carcinoma. However, the
      role of mast cells in carcinogenesis is unclear. AIM: This study explores the
      effects of mast cells on the proliferation and gene expression profile of mucosal
      squamous cell carcinoma using human mast cell line (HMC-1) and human glossal
      squamous cell carcinoma cell line (SCC25). METHODS: HMC-1 and SCC25 were co
      cultured in a two-compartment chamber, separated by a polycarbonate membrane. HMC
      1 was stimulated to degranulate with calcium ionophore A23187. The experiments
      were done in quadruplicate. Negative controls were established where SCC25 were
      cultured alone without HMC-1. At 12, 24, 48 and 72 hours, proliferation and
      viability of SCC25 were assessed with MTT colorimetric assay. cDNA microarray was
      employed to study differential gene expression between co-cultured and control
      SCC25. RESULTS: HMC-1/SCC25 co-culture resulted in suppression of growth rate for
      SCC-25 (34% compared with 110% for the control by 72 hours, p < 0.001), and
      dysregulation of genes TRAIL, BIRC4, CDK6, Cyclin G2 and CDC6 in SCC25.
      CONCLUSION: We show that mast cells have a direct inhibitory effect on the
      proliferation of mucosal squamous cell carcinoma in vitro by dysregulating key
      genes in apoptosis and cell cycle control.

PMID- 17178000
TI  - Insights on the evolution of trehalose biosynthesis.
AB  - BACKGROUND: The compatible solute trehalose is a non-reducing disaccharide, which
      accumulates upon heat, cold or osmotic stress. It was commonly accepted that
      trehalose is only present in extremophiles or cryptobiotic organisms. However, in
      recent years it has been shown that although higher plants do not accumulate
      trehalose at significant levels they have actively transcribed genes encoding the
      corresponding biosynthetic enzymes. RESULTS: In this study we show that trehalose
      biosynthesis ability is present in eubacteria, archaea, plants, fungi and
      animals. In bacteria there are five different biosynthetic routes, whereas in
      fungi, plants and animals there is only one. We present phylogenetic analyses of
      the trehalose-6-phosphate synthase (TPS) and trehalose-phosphatase (TPP) domains
      and show that there is a close evolutionary relationship between these domains in
      proteins from diverse organisms. In bacteria TPS and TPP genes are clustered,
      whereas in eukaryotes these domains are fused in a single protein. CONCLUSION: We
      have demonstrated that trehalose biosynthesis pathways are widely distributed in
      nature. Interestingly, several eubacterial species have multiple pathways, while
      eukaryotes have only the TPS/TPP pathway. Vertebrates lack trehalose biosynthetic
      capacity but can catabolise it. TPS and TPP domains have evolved mainly in
      parallel and it is likely that they have experienced several instances of gene
      duplication and lateral gene transfer.

PMID- 17178001
TI  - Population distribution and burden of acute gastrointestinal illness in British
      Columbia, Canada.
AB  - BACKGROUND: In developed countries, gastrointestinal illness (GI) is typically
      mild and self-limiting, however, it has considerable economic impact due to high
      morbidity. METHODS: The magnitude and distribution of acute GI in British
      Columbia (BC), Canada was evaluated via a cross-sectional telephone survey of
      4,612 randomly selected residents, conducted from June 2002 to June 2003.
      Respondents were asked if they had experienced vomiting or diarrhoea in the 28
      days prior to the interview. RESULTS: A response rate of 44.3% was achieved. A
      monthly prevalence of 9.2% (95% CI 8.4-10.0), an incidence rate of 1.3 (95% CI
      1.1-1.4) episodes of acute GI per person-year, and an average probability that an
      individual developed illness in the year of 71.6% (95% CI 68.0-74.8), weighted by
      population size were observed. The average duration of illness was 3.7 days,
      translating into 19.2 million days annually of acute GI in BC. CONCLUSION: The
      results corroborate those from previous Canadian and international studies,
      highlighting the substantial burden of acute GI.

PMID- 17178003
TI  - Medical science, culture, and truth.
AB  - There is a fairly closed circle between culture, language, meaning, and truth
      such that the world of a given culture is a world understood in terms of the
      meanings produced in that culture. Medicine is, in fact, a subculture of a
      powerful type and has its own language and understanding of the range of
      illnesses that affect human beings. So how does medicine get at the truth of
      people and their ills in such a way as to escape its own limited constructions?
      There is a way out of the closed circle implicit in the idea of a praxis and the
      engagement with reality that is central to it and the further possibility
      introduced by Jacques Lacan that signification is never comprehensive in relation
      to the subject's encounter with the real. I will explore both of these so as to
      develop a conception of truth that is apt for the knowledge that arises in the
      clinic.

PMID- 17178002
TI  - Seroepidemiology of Toxoplasma gondii infection in psychiatric inpatients in a
      northern Mexican city.
AB  - BACKGROUND: Patients with psychiatric disorders were found to show a high
      seroprevalence of Toxoplasma gondii infection. There is scarce information about
      the epidemiology of T. gondii infection in psychiatric patients in Mexico.
      Therefore, we sought to determine the prevalence of T. gondii infection and
      associated socio-demographic, clinical and behavioural characteristics in a
      population of psychiatric patients in Durango City, Mexico. Seroprevalence in
      patients was compared with that obtained in a control population. METHODS: One
      hundred and thirty seven inpatients of a public psychiatric hospital and 180
      controls were examined for the presence of IgG and IgM antibodies against T.
      gondii by enzyme-linked immunoassay (Diagnostic Automation Inc., Calabasas, CA,
      USA). The control population consisted of blood donors of a public blood bank and
      elderly persons attending a senior center in the same city. Age in controls (42
      years +/- 20.2) was comparable with that of the psychiatric patients (43.7 years
      +/-13.8) (p = 0.42). Socio-demographic, clinical and behavioral characteristics
      from the patients were also obtained. RESULTS: Anti-T. gondii IgG antibodies
      indicating latent infection with T. gondii was found in 25 (18.2%) of 137
      psychiatric inpatients and 16 (8.9%) of 180 controls (p = 0.02). Ten (26.3%) of
      38 schizophrenic patients had latent infection and this prevalence was also
      significantly higher than that observed in controls (p = 0.005). Prevalence of
      anti-T. gondii IgM antibodies was comparable among patients and controls (4.4% vs
      2.2%, respectively, p = 0.22). Multivariate analysis showed that T. gondii
      infection in inpatients was positively associated with sexual promiscuity
      (adjusted OR = 15.8; 95% CI: 3.8-64.8), unwashed raw fruit consumption (adjusted
      OR = 5.19; 95% CI: 2.3-11.3), and a history of surgery (adjusted OR = 6.5; 95%
      CI: 2.6-16), and negatively associated with lamb meat consumption (adjusted OR =
      0.26; 95% CI: 0.10-0.63). CONCLUSION: In the present study, psychiatric
      inpatients in Durango, Mexico, in general and schizophrenia inpatients in
      particular had a significantly higher prevalence of T. gondii infection than the
      control group. Results suggest that unwashed raw fruit consumption might be the
      most important route of T. gondii transmission in our psychiatric inpatients
      while lamb meat consumption the less important. Additional studies will have to
      elucidate the causative relation between infection with T. gondii and psychiatric
      disorders.

PMID- 17178006
TI  - Communicating population health statistics through graphs: a randomised
      controlled trial of graph design interventions.
AB  - BACKGROUND: Australian epidemiologists have recognised that lay readers have
      difficulty understanding statistical graphs in reports on population health. This
      study aimed to provide evidence for graph design improvements that increase
      comprehension by non-experts. METHODS: This was a double-blind, randomised,
      controlled trial of graph-design interventions, conducted as a postal survey.
      Control and intervention participants were randomly selected from telephone
      directories of health system employees. Eligible participants were on duty at the
      listed location during the study period. Controls received a booklet of 12 graphs
      from original publications, and intervention participants received a booklet of
      the same graphs with design modifications. A questionnaire with 39 interpretation
      tasks was included with the booklet. Interventions were assessed using the ratio
      of the prevalence of correct responses given by the intervention group to those
      given by the control group for each task. RESULTS: The response rate from 543
      eligible participants (261 intervention and 282 control) was 67%. The prevalence
      of correct answers in the control group ranged from 13% for a task requiring
      knowledge of an acronym to 97% for a task identifying the largest category in a
      pie chart. Interventions producing the greatest improvement in comprehension
      were: changing a pie chart to a bar graph (3.6-fold increase in correct point
      reading), changing the y axis of a graph so that the upward direction represented
      an increase (2.9-fold increase in correct judgement of trend direction), a
      footnote to explain an acronym (2.5-fold increase in knowledge of the acronym),
      and matching the y axis range of two adjacent graphs (two-fold increase in
      correct comparison of the relative difference in prevalence between two
      population subgroups). CONCLUSION: Profound population health messages can be
      lost through use of overly technical language and unfamiliar statistical
      measures. In our study, most participants did not understand age standardisation
      and confidence intervals. Inventive approaches are required to address this
      problem.

PMID- 17178005
TI  - Value of serum glycated albumin and high-sensitivity C-reactive protein levels in
      the prediction of presence of coronary artery disease in patients with type 2
      diabetes.
AB  - BACKGROUND: Coronary artery disease (CAD) is a major vascular complication of
      diabetes mellitus and reveals high mortality. Up to 30% of diabetic patients with
      myocardial ischemia remain asymptomatic and are associated with worse prognosis
      compared to non-diabetic counterpart, which warrants routine screening for CAD in
      diabetic population. The purpose of this study was to evaluate the clinical value
      of serum glycated albumin and high-sensitivity C-reactive protein (hs-CRP) levels
      in predicting the presence of CAD in patients with type 2 diabetes. METHODS:
      Three hundred and twenty-four patients with type 2 diabetes were divided into two
      groups based on presence (CAD group, n = 241) or absence (control group, n = 83)
      of angiographically-documented CAD (lumen diameter narrowing > or =70%). Serum
      levels of glycated albumin and hs-CRP as well as serum concentrations of glucose,
      lipids, creatinine, blood urea nitrogen and uric acid were measured in both
      groups. Predictors of CAD were determined using multivariate logistic regression
      model and receiver-operating characteristic (ROC) curves. RESULTS: Serum glycated
      albumin and hs-CRP levels were significantly increased in diabetic patients with
      CAD. Multivariate regression analysis revealed that male gender, age, serum
      levels of glycated albumin, hs-CRP, creatinine and lipoprotein (a) were
      independent predictors for CAD. Areas under the curve of glycated albumin and hs
      CRP and for regression model were 0.654 (95%CI 0.579-0.730, P < 0.001), 0.721
      (95%CI 0.658-0.785, P < 0.001) and 0.824 (95% CI 0.768-0.879, P < 0.001),
      respectively. The optimal values of cut-off point were 18.7% (sensitivity 67.9%,
      specificity 60.0%) for glycated albumin and 5.2 mg/l (sensitivity 72.2%,
      specificity 60.0%) for hs-CRP to predict CAD. Logistic regression model was
      defined as: P/(1-P) = EXP(-1.5 + 1.265 gender + 0.812 age + 1.24 glycated albumin
      + 0.953 hs-CRP + 0.902 lipoprotein(a) + 1.918 creatinine). The optimal
      probability value for predicting CAD in type 2 diabetic patients was 0.648
      (sensitivity 82.3%, specificity 68.6%). CONCLUSION: Serum glycated albumin and hs
      CRP levels were significantly elevated in patients with type 2 diabetes and CAD.
      The logistic regression model incorporating with glycated albumin, hs-CRP and
      other major risk factors of atherosclerosis may be useful for screening CAD in
      patients with type 2 diabetes.

PMID- 17178004
TI  - Unsupervised clustering of gene expression data points at hypoxia as possible
      trigger for metabolic syndrome.
AB  - BACKGROUND: Classification of large volumes of data produced in a microarray
      experiment allows for the extraction of important clues as to the nature of a
      disease. RESULTS: Using multi-dimensional unsupervised FOREL (FORmal ELement)
      algorithm we have re-analyzed three public datasets of skeletal muscle gene
      expression in connection with insulin resistance and type 2 diabetes (DM2). Our
      analysis revealed the major line of variation between expression profiles of
      normal, insulin resistant, and diabetic skeletal muscle. A cluster of most
      "metabolically sound" samples occupied one end of this line. The distance along
      this line coincided with the classic markers of diabetes risk, namely obesity and
      insulin resistance, but did not follow the accepted clinical diagnosis of DM2 as
      defined by the presence or absence of hyperglycemia. Genes implicated in this
      expression pattern are those controlling skeletal muscle fiber type and
      glycolytic metabolism. Additionally myoglobin and hemoglobin were upregulated and
      ribosomal genes deregulated in insulin resistant patients. CONCLUSION: Our
      findings are concordant with the changes seen in skeletal muscle with altitude
      hypoxia. This suggests that hypoxia and shift to glycolytic metabolism may also
      drive insulin resistance.

PMID- 17178008
TI  - Post-lactational mammary gland regression: molecular basis and implications for
      breast cancer.
AB  - During pregnancy, there is a massive increase in the number of luminal epithelial
      cells in the breast, which are destined to become the milk factories after birth.
      These cells are no longer required when the young are weaned, and are removed in
      a carefully orchestrated event called involution. In this process, the secretory
      epithelial cells die and are replaced by adipocytes, which redifferentiate as the
      epithelium is removed. It is essential that the gland is properly remodelled to a
      pre-pregnant state so that successful lactation can occur following a subsequent
      pregnancy. Furthermore, failure to remove unnecessary lactational alveoli during
      weaning could result in inflammation and tissue damage. Recently, it has been
      shown that components in the fatty stroma in involuting breast can promote
      metastasis. Thus, it is important to understand the molecular mechanisms that
      regulate involution, how these can fail, the consequences of the remodelling
      process, and how this knowledge can inform us about breast cancer. In this
      review, I discuss the roles of the JAK-STAT, NF-kappaB and other signalling
      pathways in the regulation of apoptosis and tissue remodelling during involution.

PMID- 17178007
TI  - Arsenic trioxide, a potent inhibitor of NF-kappaB, abrogates allergen-induced
      airway hyperresponsiveness and inflammation.
AB  - BACKGROUND: Overactivation of nuclear factor kappaB (NF-kappaB) orchestrates
      airway eosinophilia, but does not dampen airway hyperresponsiveness in asthma. NF
      kappaB repression by arsenic trioxide (As2O3) contributes to apoptosis of
      eosinophils (EOS) in airways. Here we provide evidence that As2O3 abrogates
      allergen (OVA)-induced airway eosinophilia by modulating the expression of
      IkappaBalpha, an NF-kappaB inhibitory protein, and decreases the airway
      hyperresponsiveness. METHODS: Using a murine model of asthma, the airway
      hyperresponsiveness was conducted by barometric whole-body plethysmography.
      Airway eosinophilia, OVA-specific IgE in serum, and chemokine eotaxin and RANTES
      (regulated upon activation, normal T cell expressed and secreted) in
      bronchoalveolar lavage fluid were measured by lung histology, Diff-Quick
      staining, and ELISA. Chemokine-induced EOS chemotactic activity was evaluated
      using EOS chemotaxis assay. Electrophoretic mobility shift assay and Western blot
      analysis were performed to assess pulmonary NF-kappaB activation and IkappaBalpha
      expression, respectively. RESULTS: As2O3 attenuated the allergen-induced serum
      IgE, chemokine expression of eotaxin and RANTES, and the EOS recruitment in
      bronchoalveolar lavage fluid, which is associated with an increased IkappaBalpha
      expression as well as a decreased NF-kappaB activation. Also, As2O3 suppressed
      the chemotaxis of EOS dose-dependently in vitro. Additionally, As2O3
      significantly ameliorated the allergen-driven airway hyperresponsiveness, the
      cardinal feature underlying asthma. CONCLUSION: These findings demonstrate an
      essential role of NF-kappaB in airway eosinophilia, and illustrate a potential
      dissociation between airway inflammation and hyperresponsiveness. As2O3 likely
      exerts its broad anti-inflammatory effects by suppression of NF-kappaB activation
      through augmentation of IkappaBalpha expression in asthma.

PMID- 17178009
TI  - Resting and postexercise cardiac autonomic control in trained master athletes.
AB  - This study used measures of heart rate variability during recovery from high
      intensity exercise in trained Master athletes to examine postexercise cardiac
      autonomic regulation. Seven males (mean age 52.1 +/- 3.3 yr; mass 85.1 +/- 18.0
      kg) and 6 females (mean age 50.5 +/- 2.9 yr; mass 63.1 +/- 6.0 kg) performed
      incremental exercise to an intensity that induced a >4.5 mmol capillary blood
      lactate concentration, followed by incremental exercise to volitional exhaustion
      (VO2(max)). A 6 min ECG recording before (Pre) and after (Post) exercise was
      analyzed in the time (mean rr interval, sd rr) and frequency domains (total
      power, very low frequency [VLF: 0-0.04 Hz], low frequency [LF: 0.04-0.15 Hz],
      high frequency [HF: 0.15-0.4 Hz]). VO2(max) for males and females was 49.4 +/-
      7.1 ml kg(-1) min(-1) and 45.1 +/- 10.1 ml kg(-1) min(-1), respectively. Lower
      mean rr interval (Pre: 1,048 +/- 128 ms; Post: 730 +/- 78 ms; P < 0.001) and
      lower sd rr (Pre: 77 +/- 30 ms; Post: 43 +/- 17 ms; P < 0.001) were recorded
      following exercise, with no differences based on gender. Total power decreased
      following exercise (Pre: 6,331 +/- 6,119 ms; Post: 1,921 +/- 1,552 ms). When
      normalized for changes in total power, a decreased HF component (Pre: 34.52 +/-
      14.79 n.u.; Post: 18.49 +/- 13.64 n.u.; P < 0.05) with no change in LF component
      (Pre: 61.00 +/- 18.66 n.u.; Post: 69.63 +/- 23.97 n.u.; P = 0.34) was recorded.
      No gender differences in HRV in the frequency domain were recorded. Decreased
      heart rate variability in both time and frequency domains suggested an increased
      parasympathetic withdrawal during the autonomic control of postexercise
      tachycardia in trained Master athletes.

PMID- 17178010
TI  - Cognitive performance after carotid angioplasty and stenting with brain
      protection devices.
AB  - OBJECTIVE: Neuropsychological outcomes after carotid endarterectomy (CEA) have
      been investigated extensively. However, cognitive impacts of carotid angioplasty
      and stenting (CAS), an emerging alternative to CEA, have not been studied. This
      study is aimed at investigating pattern and degree of cognitive changes after CAS
      among patients with high-grade carotid stenosis. PATIENTS AND METHODS: Fifty-four
      patients with high-grade carotid artery stenosis and received elective CAS were
      followed. Sixty-six patients with similar medical conditions requiring carotid
      angiography (CAG) were enrolled as controls. Cognitive functions among patients
      in both groups were evaluated at baseline and follow-ups utilizing a battery of
      neuropsychometric tests. Results were analysed by inter-group and within-group
      comparisons. RESULTS: There were no statistically significant differences between
      CAS and CAG patients regarding demographic characteristics, risk factors for
      stroke and baseline cognitive performance (p>0.05). CAS patients performed
      significantly better than CAG patients in Rey auditory verbal learning tests
      (RAVLT) at week 1 (41.2 +/- 5.2 versus 37.4 +/- 4.0, p<0.001) and week 12 follow
      ups (43.3 +/- 7.7 versus 37.3 +/- 4.5, p<0.001). Comparison of z score also
      indicated CAS patients improved significantly more than CAG patients in RAVLT at
      both weeks 1 (1.08 +/- 1.29 versus 0.25 +/- 0.99, p<0.001) and 12 follow-ups
      (1.62 +/- 1.95 versus 0.05 +/- 1.02, p<0.001). CONCLUSION: CAS patients
      demonstrated improvement in verbal memory after procedures. Correction of
      cerebral hypoperfusion and reduction of artery-to-artery embolization after CAS
      are postulated responsible for the cognitive improvement.

PMID- 17178013
TI  - Nutrition and cancer risk: an overview.
AB  - The role of diet in cancer is a major public health issue Foods associated with a
      low risk of cancer are those typically included in the so-called Mediterranean
      diet, which is also associated with low mortality rates from cardiovascular
      disease. Implementing such a diet would involve increasing the consumption of
      fruits, vegetables, cereals, whole-grain foods and fish, while reducing the
      intake of refined carbohydrates and red meat. In addition, olive oil should
      replace saturated fats. Omega-3 fatty acids found in fish inhibit the growth in
      vitro of colon, breast and prostate cancers. Fibre can bind bile acids, which
      produce carcinogenic metabolites, and fermented fibre produces volatile fatty
      acids that can protect against colon cancer. It has been hypothesized that the
      anti-cancer actions of olive oil may relate to the ability of its mono
      unsaturated fatty acid, oleic acid, to regulate oncogenes.

PMID- 17178014
TI  - Polycystic ovary syndrome and the postmenopausal woman.
AB  - Polycystic ovary syndrome (PCOS) is a common syndrome among young women. It is
      associated with fertility problems, clinical manifestations of hyperandrogenism
      and metabolic disturbance, particularly insulin resistance. The long-term
      consequences of PCOS have not been fully determined, but there is an increased
      risk of progression to diabetes and an increase in cardiovascular risk factors.
      The extent to which PCOS is present in postmenopausal women and the degree to
      which it increases various risk factors in addition to the known risk of the
      postmenopausal period are not yet known. This paper reviews the pathophysiology
      of PCOS and its long-term consequences and considers the evidence to date that is
      applicable to the postmenopausal woman.

PMID- 17178015
TI  - Sexuality and the menopause.
AB  - Sexual problems such as dyspareunia and decreased sexual desire are common after
      the menopause. Hypoactive sexual desire disorder is the diagnostic category
      applied to many women with loss or lack of sexual interest or desire. The
      principal components of assessment for sexual dysfunction in menopausal women
      are: a general, gynaecological, obstetric, psychiatric, psychosexual and
      relationship history; use of self-report questionnaires; physical examination;
      and hormonal evaluation. The use of low-dose vaginal estrogen tablets, rings,
      creams or pessaries may help to improve local genital response but does not
      necessarily improve sexual interest or motivation. An improvement in sexual
      function has been reported with tibolone and a combination of estrogen and
      androgen therapy, al though it remains unclear which groups of postmenopausal
      women with sexual problems will benefit most from such treatments. Where there is
      no response to estrogens or where there is premature or surgical menopause the
      addition of an androgen may be necessary, particularly if the free testosterone
      levels are low.

PMID- 17178016
TI  - Hysterectomy and sexual function.
AB  - Hysterectomy is one of the most common major gynaecological operations performed
      in the UK and the USA. Its impact on sexual function is a major cause of
      preoperative anxiety. Unfortunately, this anxiety is seldom articulated by
      patients, nor recognized and discussed by clinicians. Reports about the impact of
      hysterectomy on sexual function have been conflicting, partly due to the use of
      different and often unsatisfactory parameters to assess sexual function. The aim
      of this review is to assess the current evidence about the effect of hysterectomy
      on sexual function. Female sexual function is governed by psychological, social
      and physiological factors. A new model of 'the sexual response cycle', comprising
      physical, emotional and cognitive feedback, helps explain the sexual difficulties
      that arise before and after hysterectomy. Evidence is lacking for sexual
      dysfunction caused by the disruption of local nerve and blood supply, or by
      changing anatomical relationships. Removal of the ovaries at hysterectomy is
      associated with no change or even an improvement in sexual function, particularly
      in women on hormone replacement therapy. Thus, overall, hysterectomy improves
      sexual function, regardless of surgical method or removal of the cervix. This is
      probably due to the amelioration of the symptoms that have previously had a
      negative effect on sexual function.

PMID- 17178017
TI  - Cognitive function testing: the case for standardization and automation.
AB  - This review considers the advantages that both standardization and automation of
      cognitive function testing can bring to clinical research. It reviews progress
      made in several fields of medicine with a standardized and automated cognitive
      function assessment system which has been in use in worldwide clinical trials for
      over 20 years. Data are presented showing the effects on cognitive function of
      both normal ageing and a variety of diseases. The utility of cognitive testing in
      the identification and classification of dementia is considered, and its ability
      to further our understanding of the cognitive sequelae of stroke is discussed.
      The correlation between assessments of cognitive function and patients' ability
      to undertake the activities of daily living is evaluated. Finally, the use of
      such techniques to identify beneficial effects of treatment in various conditions
      is described. The review concludes that standardization and automation of
      cognitive function testing have facilitated progress in a number of fields, and
      that the systematic application of such a technique in menopause research would
      greatly help advance our knowledge in this field.

PMID- 17178018
TI  - Health benefits of weight reduction in postmenopausal women: a systematic review.
AB  - The objective of this systematic review was to determine the effect on long-term
      health outcomes of lifestyle interventions designed to produce weight loss in
      postmenopausal women. A systematic search of the MEDLINE, EMBASE, PsychINFO and
      CINAHL databases retrieved four randomized controlled trials (RCTs) and one
      controlled clinical trial (CCT) of at least 24 weeks' duration as well as one
      systematic review. The majority of the studies recruited from the community, had
      samples with similar baseline characteristics and assessed completers only. Drop
      out rates varied from 2.5% to 16%. All active-treatment arms demonstrated
      significant improvements in weight and body composition from baseline.
      Significant effects between treatment groups were shown only in intervention
      versus control studies. Significant weight loss was not accompanied by beneficial
      changes in cardiovascular risk factors in the majority of studies. None of the
      studies of weight loss reported disease outcomes. Weight loss in active-treatment
      arms varied from 1.5 kg to 9 kg over 6-12 months. The study that produced the
      greatest weight loss demonstrated improvements in risk factors and it may be that
      only this one study produced sufficient weight loss to do so. Many of the studies
      were probably underpowered and too short in duration to detect change in risk
      factors. Lifestyle interventions do produce weight loss in overweight
      postmenopausal women and have the potential to improve disease outcomes
      associated with overweight.

PMID- 17178019
TI  - Controversies in the use of adjuvant trastuzumab (Herceptin).
AB  - Over-expression of the human epidermal growth factor receptor 2 (HER2) protein,
      amplification of the HER2 gene or both occur in 15-25% of breast cancers and are
      associated with aggressive tumour behaviour. Trastuzumab (Herceptin), a humanized
      murine monoclonal antibody against the HER2 protein, has been shown to benefit
      patients with HER2-positive metastatic breast cancer when administered alone or
      in combination with chemotherapy. When to start therapy, the duration of
      treatment, adjuvant chemotherapy regimens and cardiotoxicity issues are examined.

PMID- 17178020
TI  - Reproductive ageing, sex steroids and depression.
AB  - Perimenopausal depression affects a considerable number of women and is
      associated with significant disability and morbidity. Major and minor depressions
      are the two most prevalent forms of acute depressive illness. Major depression
      has an estimated lifetime prevalence of 17% and affects approximately twice as
      many women as men. While the relationship between the onset of depressive illness
      and reproductive senescence is controversial, epidemiological and clinic-based
      studies that have distinguished between the perimenopause and the postmenopause
      have documented that, for some middle-aged women, the perimenopause is associated
      with an increased vulnerability to depression. Future studies of perimenopausal
      depression should identify the number of women affected, individual risk factors
      and the role of hormonal therapies in this condition.

PMID- 17178021
TI  - Mammographic density: a hormonally responsive risk factor for breast cancer.
AB  - Mammographic density refers to radiologically dense breast tissue, and reflects
      variations in the tissue composition of the breast. It is positively associated
      with collagen and epithelial and non-epithelial cells, and negatively associated
      with fat. There is extensive evidence that mammographic density is a risk factor
      for breast cancer, independent of other risk factors, and is associated with
      large relative and attributable risks for the disease. The epidemiology of
      mammographic density, notably the inverse association with age, is consistent
      with it being a marker of susceptibility to breast cancer. Cumulative exposure to
      mammographic density may be an important determinant of the age-specific
      incidence of breast cancer in the population. All risk factors for breast cancer
      must ultimately exert their influence by an effect on the breast, and these
      findings suggest that, for at least some risk factors, this influence includes an
      effect on the number of cells and the quantity of collagen in the breast, which
      is reflected in differences in mammographic density. Many of the genetic and
      environmental factors that influence the risk of breast cancer affect the
      proliferative activity and quantity of stromal and epithelial tissue in the
      breast, and these effects are reflected in differences in mammographic density
      among women of the same age. Some of these influences include endogenous and
      exogenous hormones, and the menopause. A better understanding of the factors that
      influence the response of breast tissue to these hormonal exposures may lead to
      an improved understanding of the aetiology of mammographic density and of breast
      cancer.

PMID- 17178029
TI  - Protection of androgen against hypoxic-ischemic brain damage in neonatal rats and
      possible mechanisms.
AB  - OBJECTIVE: Some research has shown that androgen has a neuroprotection against
      hypoxia-ischemia brain damage (HIBD). However, the relevant mechanism has not
      been fully elucidated. This study aimed to explore the neuroprotection of
      androgen against HIBD in neonatal rats and the possible mechanism. METHODS: Sixty
      four seven-day-old Sprague-Dawley (SD) rats were randomly assigned into three
      groups: Sham-operation, HIBD and Androgen. The HIBD model was induced by ligation
      of the left carotid common artery along with hypoxia exposure in neonatal rats
      from the latter two groups. The Sham-operation group was not subjected to hypoxia
      ischemia (HI). The Androgen intervention group received an injection of
      testosterone propionate (25 mg/kg) immediately after HIBD. Bcl-2 and Bax protein
      expressions in the cortex and hippocampal CA region were detected by
      immunohistochemical method at 6, 24 and 72 hrs and at 7 days after HI. The
      contents of SOD and MDA in the brain tissue homogenate were measured by the
      thiobarbituric acid (TBA) method and the xanthine oxidase luminescence method
      respectively at 6, 24 and 48 hrs after HI. RESULTS: There were few Bcl-2 and Bax
      immune positive cells in the cortex or hippocampus in the left hemisphere in the
      Sham-operation group at 6 hrs after operation. This was significantly different
      from the HIBD control and Androgen intervention groups (P < 0.01). The expression
      of Bcl-2 protein in the cortex and hippocampus of the Androgen intervention group
      was significantly higher than that of the HIBD control group at 6, 24 and 72 hrs
      after HI (P < 0.05 or 0.01). The expression of Bax protein in the cortex and
      hippocampus of the Androgen intervention group was significantly lower than that
      of the HIBD control group at 24 hrs after HI (P < 0.05). The SOD content in the
      brain tissue homogenate of the HIBD control group was significantly reduced, in
      contrast, the MDA content in the brain tissue homogenate of the HIBD control
      group increased significantly at 6 hrs after HI compared with the Sham-operation
      group (P < 0.05). The SOD content was reduced to a nadir and the MDA content
      increased to a peak at 24 hrs after HI in the HIBD control group. Androgen
      intervention increased significantly the SOD activity at 6,24 and 48 hrs after HI
      and decreased significantly the MDA content at 6 and 24 hrs after HI as compared
      with the HIBD control group (P < 0.05 or 0.01). CONCLUSIONS: The neuroprotection
      of androgen against neonatal HIBD is produced possibly through an increase of Bcl
      2 protein expression and a reduction in Bax protein expression, thus decreasing
      neuronal apoptosis after HI. There may also be a reduction in the consumption of
      antioxidant and an inhibition of the formation of oxidant free radicals to
      alleviate neuronal damage following HI.

PMID- 17178030
TI  - [Examination of cerebral electrical admittance plethysmogram in healthy
      newborns].
AB  - OBJECTIVE: Cerebral electrical admittance plethysmography is a novel noninvasive
      technique for evaluating cerebral hemodynamics. This study aimed to measure the
      reference values of cerebral electrical admittance plethysmogram in healthy
      newborns. METHODS: Bilateral cerebral electrical admittance plethysmography was
      performed in 40 healthy newborns. RESULTS: The values of various indexes of
      cerebral electrical admittance plethysmogram in 40 newborns were obtained by this
      technique. The index of Admittance Differential Loop (ADL) I+II at the third and
      fourth days after birth was significantly higher than that at the first day of
      life (P < 0.05). There were significant differences in the index of ADL I+II and
      the ratio of Hs to b-S (Hs/ b-S) among different birth weight groups (P < 0.05).
      No significant differences were found in all the indexes of cerebral electrical
      admittance plethysmogram between the left and right brain of newborns. Gender and
      parturition mode had also no effects on these indexes. CONCLUSIONS: The research
      reported the reference values of cerebral electrical admittance plethysmogram in
      healthy newborns. The postnatal age and birth weight are influencing factors for
      the cerebral electrical admittance plethysmogram.

PMID- 17178031
TI  - [Serum growth hormone and prolactin levels in neonates with hypoxic-ischemic
      encephalopathy].
AB  - OBJECTIVE: To investigate the levels and roles of serum growth hormone (GH) and
      prolactin (PRL) in neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: Serum
      GH and PRL levels were measured by radioimmunoassay in 54 neonates with HIE (20
      mild, 19 moderate and 15 severe HIE) at the acute and convalescence stages.
      Twenty normal neonates were used as controls. RESULTS: Serum GH levels were
      significantly lower, but PRL levels were significantly higher in moderate and
      severe HIE neonates at the acute stage compared with those of controls and mild
      HIE neonates (P < 0.01). There were noticeable differences in serum levels of GH
      and PRL between the moderate and severe HIE cases (P < 0.01). During the
      convalescence stage, serum GH levels increased and PRL levels decreased in
      moderate and severe HIE neonates compared with those at the acute stage (P <
      0.01); serum GH and PRL levels in each sub-group of HIE restored to the levels of
      controls. There was a closely negative correlation between GH and PRL levels at
      the acute stage of HIE (r = -0.8759, P < 0.01). CONCLUSIONS: GH and PRL might be
      involved in the pathophysiological process of HIE. The levels of GH and PRL
      closely relate to the severity of HIE at the acute stage.

PMID- 17178032
TI  - [Gene mutation of high affinity immunoglobulin E receptor beta-chain in children
      with asthma].
AB  - OBJECTIVE: To investigate the association of the polymorphism of I181L, V183L and
      E237G in the high affinity immunoglobulin E receptor beta-chain (FcepsilonR1beta)
      with the susceptibility of childhood asthma and the serum total immunoglobulin E
      (IgE) level. METHODS: The coding variants of I181L, V183L and E237G and the serum
      total IgE level were detected using amplification refractory mutation
      systemdouble ended arrowpolymerase chain reaction (ARMS-PCR) and double antibody
      sandwich ELISA respectively in 50 asthmatic children and 40 normal controls from
      Sichuan Province. The association of gene mutation with the susceptibility of
      asthma and the serum total IgE level was analyzed. RESULTS: There were 5 cases of
      I181L mutation, 2 of V183L mutation, and 7 of E237G mutation in the Asthmatic
      group. There was no mutation in the Normal control group. The frequency of I181L
      and E237G mutation in the Asthmatic group were statistically higher than in the
      Normal control group (P < 0.01). The serum total IgE level in the Asthmatic
      subgroup with I181L mutation (2.837 +/- 0.407) or E237G mutation (3.044 +/-
      0.419) was significantly higher than in the Asthmatic subgroup without gene
      mutation (2.156 +/- 0.638) and the Normal control group (1.348 +/- 1.291) (P <
      0.05 or 0.01). CONCLUSIONS: The polymorphism of Fc epsilonR1betaI181L and E237G
      is a susceptible gene of childhood asthma and closely associates with the
      increased serum total IgE level.

PMID- 17178033
TI  - [Atopy spectrum and its relationship with clinical characteristics in asthmatic
      children under 4 years of age].
AB  - OBJECTIVE: To study the atopy spectrum and the influence of clinical
      characteristics upon it in asthmatic children under 4 years of age. METHODS:
      Clinical data of 62 asthmatic children under 4 years of age, including age, sex,
      the age of first wheezing attack, the total times of wheezing attack, the
      duration of history of wheezing, and the allergic history of both children and
      parents, were collected. The screening tests on allergens (fx5E, mx2 and
      Phadiatop) were conducted by fluoroenzyme-immunometric assay using the UniCAP100
      system. The total serum IgE level was also measured. Logistic regression was used
      to analyze the effect of clinical characteristics on allergic sensitization.
      RESULTS: The positive rates of fx5E, mx2 and Phadiatop were 40.3%, 14.5% and
      14.5% respectively, and the total allergic sensitization screening test rate was
      46.8%. The sensitization rate to inhalant allergens was 24.2%. The allergic
      history of parent (s), the sensitization to food allergens, the age of first
      wheezing attack and total serum IgE level were main factors influencing the
      sensitization to inhalant allergens. CONCLUSIONS: About a quarter of asthmatic
      children under 4 years of age showed sensitization to inhalant allergens. The
      asthmatic history of parent (s), the sensitization to food allergens, the age of
      first wheezing attack greater than 2 years and the significantly higher total
      serum IgE level may increase the possibility of sensitization to inhalant
      allergens in asthmatic children under 4 years of age.

PMID- 17178034
TI  - [Levels of intracellular IL-6 and IFN-gamma in children with acute lymphoblastic
      leukemia].
AB  - OBJECTIVE: To study the changes of intracellular interleukin-6 (IL-6) and
      interferon-gamma (IFN-gamma) expressions in children with acute lymphoblastic
      leukemia (ALL) at different stages, and to examine the correlation between IL-6
      and IFN-gamma in ALL children. METHODS: The levels of intracellular IL-6 and IFN
      gamma in venous blood lymphocytes were detected by flow cytometry in 42 children
      with ALL at diagnosis and at remission stage. Twenty healthy children were used
      as the controls. RESULTS: The intracellular IL-6 level in ALL children at
      diagnosis was 81.74+/-9.31, which was much higher than that in the Control group
      (5.67 +/- 0.96 ) (P < 0.01). The intracellular IFN-gamma level in ALL children
      (1.31 +/- 0.32) was significantly lower than that in the Control group (1.46 +/-
      0.49) (P < 0.01). However, the intracellular IL-6 level (27.52 +/- 3.40)
      decreased remarkably in ALL patients at remission stage (P < 0.01), but was still
      higher than that in the Control group (P < 0.01). In contrast, the intracellular
      IFN-gamma level (1.97 +/- 0.72) increased noticeably in ALL patients at remission
      stage, which was higher than that at diagnosis and the Control group (P < 0.01).
      A negative correlation was found between the intracellular IL-6 and the IFN-gamma
      levels in ALL patients (r=-0.476, P < 0.05). CONCLUSIONS: Intracellular IL-6 and
      IFN-gamma levels may be used as the markers for monitoring the response to
      treatment in ALL patients. There is a negative correlation between intracellular
      IL-6 and IFN-gamma levels in ALL children.

PMID- 17178035
TI  - [Role of probiotics in the prevention of neonatal necrotizing enterocolitis: A
      case-control study].
AB  - OBJECTIVE: To assess the role of probiotics in the prevention of neonatal
      necrotizing enterocolitis (NEC) and to investigate the risk factors for NEC.
      METHODS: A total of 2528 hospitalized neonates between January 2002 and May 2005
      were assigned into either receiving prophylactic use of probiotics bifoco
      (Prevention group, n=1182) or without probiotics supplementation (Control group,
      n = 1346). The incidence of NEC was compared between the two groups. The risk
      factors for NEC were investigated by conditional logistic regression
      multifactorial analysis. RESULTS: There were 19 cases of NEC in the Control group
      (1.41%), but only 6 cases in the Prevention group (0.51%) (P < 0.05). Gestational
      age (OR = 5.521), hypoxicdouble ended arrowischemic encephalopathy (OR = 3.887),
      specticemia (OR = 4.854) and critical illness scores (OR = 5.989) were the risk
      factors for NEC, while the prophylactic use of probiotics was an independent
      protective factor for NEC (OR = 0.255). CONCLUSIONS: The prophylactic use of
      probiotics may reduce the incidence of NEC in neonates.

PMID- 17178036
TI  - [Concentrations of serum iron and transferrin in children with nephrotic
      syndrome].
AB  - OBJECTIVE: Nephrotic syndrome (NS) is characterized by marked urinary excretion
      of albumin and other intermediated-size plasma proteins such as transferrin. The
      aim of this study was to determine the changes of serum iron and transferrin and
      the relationship between the serum and urinary transferrin. METHODS: The indexes
      related to iron metabolism, including serum iron, ferritin, transferrin, total
      iron-binding capacity, transferrin saturation and hematological parameters (Hb,
      MCV, MCH), and urinary transferrin were measured in 37 children with NS before
      treatment and at the remission stage. Thirty-five age-matched healthy children
      served as controls. RESULTS: Serum iron levels (18.8 +/- 3.8 micromol/L) in NS
      patients before treatment were significantly lower than in the healthy controls
      (22.2 +/-3.8 micromol/L) and those measured at the remission stage (21.0 +/- 3.5
      micromol/L) (P < 0.01). Serum transferrin levels in NS patients before therapy
      (1.9 +/- 0.3 g/L) also decreased compared with those in the healthy controls (3.1
      +/- 0.5 g/L) and those measured at the remission stage (2.9 +/- 0.6 g/L) (P <
      0.01). In contrast, serum total iron-binding capacity and transferrin saturation
      were noticeably higher in NS patients before treatment than those in the healthy
      controls (total iron-binding capacity 56.4 +/- 9.2 micromol/L vs 50.7 +/- 6.8
      micromol, P < 0.01; transferrin saturation 55.7 +/- 9.2 % vs 46.4 +/- 8.2%, P <
      0.01) and were also higher than those measured at the remission stage (51.9 +/
      7.7 micromol/L and 47.4 +/- 13.3%) (P < 0.01). Serum transferrin positively
      correlated to serum albumin (r = 0.609, P < 0.01) and negatively correlated to
      urinary transferrin (r = -0.550, P < 0.01) in NS patients before treatment.
      CONCLUSIONS: Serum iron and transferrin levels markedly decreased in NS patients,
      which may be partially related to the urinary loss of transferrin.

PMID- 17178037
TI  - [Behavioral patterns of autistic children during infancy].
AB  - OBJECTIVE: The present study investigated the behavioral patterns of autistic
      children during infancy to provide clues for early identification of childhood
      autism. METHODS: The abnormal behaviors of 30 children with autism and 26
      children with other developmental disorders in infancy were investigated.
      RESULTS: The children with autism presented a series of abnormal behaviors,
      including no social smile, no eye contact and no respond to own name, and joint
      attention deficiency, which were distinguished from the children with other
      developmental disorders. The imitation and attachment behaviors were
      significantly different between the two groups. Repetitive motor actions and
      interest peculiarity were only seen in children with autism. CONCLUSIONS: The
      children with autism may present a series of abnormal behaviors as early as in
      infancy. The abnormal behaviors facilitate early diagnosis of autism.

PMID- 17178038
TI  - [Prospective cohort study on the relationship between pathogenic bacteria in the
      nasal middle meatus and acute bacterial respiratory infection in children].
AB  - OBJECTIVE: To study the relationship between pathogenic bacteria in the nasal
      middle meatus and acute bacterial respiratory infection in children. METHODS:
      Three hundred and twenty eight children with respiratory infection (mean age 8
      years) were included into the prospective cohort study. The mucosal fluid
      specimens from the nasal middle meatus were collected under an endoscope for
      bacterial culture. The patients with bacterial culture positive were defined as
      the Exposed group and those with bacterial culture negative as the Non-exposed
      group. The grouping of the patients was blinded to the patients, patients'
      parents and physicians. Both groups received anti-virus and symptomatic
      treatments, without antibiotic administration. Five days later, the patients were
      evaluated as to whether they had bacterial infection based on the leucocyte count
      and CRP results. RESULTS: Of the 328 patients, 168 had a positive nasal bacterial
      culture. The incidence of bacterial respiratory infection in the Exposed group
      [51.2% (86/168)] was significantly higher than in the Non-exposed group [13.1%
      (21/160)] (P < 0.01). The relative risk of bacterial respiratory infection
      occurrence in patients with nasal bacterial culture positive was 3.9002.
      CONCLUSIONS: The children with respiratory infection who had potential pathogenic
      bacteria in the nasal middle meatus were more prone to develop bacterial
      respiratory infection.

PMID- 17178039
TI  - [Serologic examination for childhood herpes simplex virus infection].
AB  - OBJECTIVE: This study was designed to investigate the value of serologic
      examination in the diagnosis of childhood herpes simplex virus (HSV) infection.
      METHODS: Serum samples were collected from 2 436 outpatients and inpatients. The
      samples were divided into two groups. Group 1 consisted of 321 samples which were
      assayed for HSV-1 IgG, HSV-1 IgM, HSV-2 IgG or HSV-2 IgM antibody using herpes
      simplex virus antibody kits between January 2003 and November 2005. Group 2
      consisted of 2115 samples which were assayed for HSV-2 IgG and IgM antibodies by
      TORCH testing between October 2004 and November 2005. RESULTS: In Group 1, the
      total seroprevalence of HSV infection was 44.6%, with 38.9% being HSV-1 positive
      and 15.9% HSV-2 positive; HSV-IgM positivity was found in 41.1% and 25.5% were
      HSV-IgG positive; HSV-1 seroprevalence significantly increased with age (P <
      0.05). In Group 2 the seroprevalence of HSV-2 infection was 1.9%; all of the
      samples were HSV-2 IgG positive. CONCLUSIONS: HSV serologic examination is useful
      in the diagnosis of HSV infection in children.

PMID- 17178040
TI  - [Therapeutic effect of antithymocyte/antilymphocyte globulin on severe aplastic
      anemia and therapy-related complications].
AB  - OBJECTIVE: Immunsuppressive therapy is a major therapy for severe aplastic
      anemia, and antithymocyte /antilymphocyte globulin (ATG/ALG) is usually used.
      This study investigated the therapeutic effect of ATG/ALG on severe aplastic
      anemia and explored the management of therapy-related complications. METHODS:
      Clinical data of 28 children with severe aplastic anemia who received ATG/ALG
      treatment from December, 1994 through to September, 2005 were analyzed
      retrospectively. RESULTS: Of the 28 patients, 2 were nearly cured (7.1%), 4 were
      relieved (14.3%) and 12 were improved (42.9%) based on a hemoglobin/white blood
      cell/platelet count. These results represented an overall effective rate of
      64.3%. Clinical evidence of serum sickness developed in 19 patients, manifesting
      as fever (n = 9), cutaneous eruptions (n = 12), arthralgias (n = 7), myalgia (n =
      7) and arthrocele (n = 3). Serum sickness occurred 5-17 days after ATG/ALG
      administration and lasted for 1-15 days (mean 4.4 days). Three children with mild
      serum sickness symptoms recovered without any treatment. The symptoms of the
      other 16 patients disappeared after 3-5 days of methylprednisolone treatment (10
      mg/kg daily). However, 3 patients had relapses at 2-4 days after termination of
      methylprednisolone therapy. Another course of methylprednisolone therapy was
      administered to the 3 patients until the symptoms disappeared. The patients with
      no serum sickness or with mild serum sickness had a better response to ATG/ALG
      therapy than those who had severe serum sickness (100% vs 60%; P < 0.05).
      CONCLUSIONS: ATG/ALG therapy for severe aplastic anemia is effective. Serum
      sickness is a common complication in children with severe aplastic anemia
      following ATG/ALG therapy, but can be improved by methylprednisolone application.

PMID- 17178041
TI  - [Effect of valsatan on hepatocyte growth factor in the airways of asthmatic
      rats].
AB  - OBJECTIVE: To study the effect of valsatan (angiotensin II receptor antagonist,
      AT1) on hepatocyte growth factor (HGF) in the airways and airway remodeling in
      asthmatic rats. METHODS: Thirty two rats were randomly assigned into A-D four
      groups. Group A was normal control without treatment. Groups B-D were challenged
      by ovalbumin (OVA) for 2 weeks, 4 weeks and 4 weeks respectively to induce
      asthma. Group D received intragastric administration of valsatan (30 microg/kg
      daily for 4 weeks) after OVA challenge. The expressions of HGF, angiotonin II
      (AngII) and transforming growth factor (TGF-beta1) in the airways were detected
      by immunihistochemical staining. The pathological changes of airways were
      observed by Haematoxylin and Eosin staining. RESULTS: The HGF expression of Group
      B was significantly higher than that of Group A (10.69 +/- 0.96% vs 5.49 +/-
      1.34%; P < 0.05). Group C also showed an increased HGF level (11.85 +/- 0.87%)
      compared with Group A (P < 0.05). The HGF level in Group D (15.58 +/- 1.06%) was
      significantly higer than that of both Group B and Group C (P < 0.05). The
      expressions of TGF-beta1 and AngII increased with the challenged time, while
      valsatan treatment decreased significantly the levels of both. Valsatan treatment
      attenuated airway injuries of asthmatic rats induced by OVA
      sensitization/challenge. CONCLUSIONS: HGF has protective effects on airways and
      anti-fibrotic effects. Valsatan can improve airway remodeling possibly by
      increasing HGF levels in asthmatic rats.

PMID- 17178042
TI  - [Effect of inhaled nitric oxide on surfactant protein A and mannose binding
      ability in the lung of neonatal rats with hyperoxia-induced lung injury].
AB  - OBJECTIVE: To investigate the effect of inhaled nitric oxide (NO) on surfactant
      protein A (SP-A) and mannose binding ability (MBA) in neonatal rats with
      hyperoxia-induced lung injury. METHODS: Sixty-four neonatal rats were randomly
      exposed to room air (Control group), >95% oxygen for 6 days (Hyperoxia group), 10
      ppm NO for 24 hrs (NO group), and >95% oxygen for 6 days along with 10 ppm NO for
      24 hrs (Hyperoxia + NO group). After 2 and 6 days of exposure, the lung
      pathologic changes, gene and protein expressions of SP-A and MBA were measured.
      RESULTS: The rats from the Hyperoxia group presented with obvious lung injuries.
      The SP-A expressions of mRNA (0.81 +/- 0.04 vs 1.53 +/- 0.25) and protein (59.45
      +/- 18.37 vs 89.77 +/- 16.41) in the Hyperoxia group decreased significantly 2
      days after exposure but increased significantly 6 days after exposure (SP-A mRNA
      0.81 +/- 0.02 vs 0.63 +/- 0.03; SP-A protein 93.57 +/- 13.71 vs 47.73 +/- 21.69)
      compared with those of the Control group (P < 0.05). NO treatment alleviated the
      hyperoxia-induced pathologic injuries 2 days after exposure. The SP-A mRNA
      expression (0.55 +/- 0.91) in the Hyperoxia + NO group was significantly reduced
      as compared to both the Control and Hyperoxia groups (P < 0.05), and the SP-A
      protein expression (55.12 +/- 17.53) in the Hyperoxia + NO group was noticeably
      lower than that of the Control group (P < 0.01) 2 days after exposure. The SP-A
      protein expression in the Hyperoxia + NO group (67.33 +/- 18.59) was
      significantly lower than that of the Hyperoxia group 6 days after exposure (P <
      0.05). Two days after exposure, the NO group had significantly higher MBA than
      the Control group (0.821 +/- 0.133 vs 0.58 +/- 0.158); the Hyperoxia + NO group
      had significantly higher MBA than the Hyperoxia group (0.43 +/- 0.175 vs 0.738 +/
      0.141) (P < 0.05). CONCLUSIONS: Inhaled low dose NO may decrease SP-A protein
      expression and increase MBA of the lung tissue. This lessens the pathologic lung
      injury in neonatal rats with hyperoxia.

PMID- 17178043
TI  - [Effect of vascular endothelial growth factor on apoptosis and expression of Bcl
      2 and Mcl-1 in acute leukemia cells].
AB  - OBJECTIVE: To investigate the effect of vascular endothelial growth factor (VEGF)
      on the apoptosis of human acute leukemia HL-60 cell line and to analyze the role
      of the related apoptosis genes, such as Bcl-2 and Mcl-1, in the process of
      apoptosis of human acute leukemia cells. METHODS: HL-60 cells were treated with
      different concentrations of VEGF (2 microg/L, 20 microg/L or 100 microg/L ) or 20
      mg/L of etoposide (VP16, an apoptosis inducter) alone or VEGF plus VP16. After 18
      hrs of treatment, the apoptosis rate of HL-60 cells was detected by single-cell
      gel electrophoresis and flow cytometry. The expressions of Bcl-2 and Mcl-1 of HL
      60 cells were detected by RT-PCR. The Control group did not receive any
      treatment. Immunocytochemistry was used to detect the VEGF and Mcl-1 protein in
      bone marrow cells from 8 patients with newly diagnosed or relapsed leukemia, 14
      leukemia patients in complete remission, and from 5 normal children. RESULTS:
      Different concentrations of VEGF markedly inhibited the apoptosis of HL-60 cells
      and decreased the apoptosis induced by VP16 exposure. The Bcl-2 and Mcl-1 mRNA
      and protein in HL-60 cells treated with VEGF were significantly higher than those
      in the Control group. The expressions of VEGF and Mcl-1 protein in bone marrow
      cells of the newly diagnosed and relapsed patients were significantly higher than
      in patients in complete remission. CONCLUSION: VEGF can inhibit the apoptosis of
      HL-60 cells possibly through increasing the expressions of Bcl-2 and Mcl-1 mRNA
      and protein, which may represent one of the mechanisms responsible for human
      acute leukemia. The expressions of VEGF, Bcl-2 and Mcl-1 might be used as the
      markers for the prognostic evaluation of leukemia.

PMID- 17178044
TI  - [Effect of glutamine on apoptosis of the small intestine in young rats with
      endotoxemia and its mechanism].
AB  - OBJECTIVE: To study the effect of glutamine on intestinal epithelial apoptosis by
      examining changes regarding Bcl-2 and Bax mRNA expressions in the small intestine
      of young rats with endotoxemia and to explore the protective mechanism that
      glutamine may have. METHODS: A total of 120 18-day-old rats were randomly
      assigned into Endotoxemia, Glutamine-treated and Control groups (n = 40 each).
      The endotoxemia model was established by intraperitoneal injection of endotoxin
      (4 mg/kg of O55B5 Escherichia coli lipopolysaccharide). Rats in the Glutamine
      treated group were intraperitoneally injected with N (2)-L-alanyl-L-glutamine (2
      g/kg) along with endotoxin. Rats in the Control group were intraperitoneally
      injected with an equal volume of normal saline. The entire ileum was collected at
      2, 4, 6, 24, and 72 hrs after injection. Bcl-2 and Bax mRNA expressions were
      detected by semi-quantities reverse transcriptase chain reaction. RESULTS: Bcl-2
      mRNA was not expressed in the Control and the Endotoxemia groups but increased in
      the Glutamine-treated group at each time point. Bax mRNA expression was weak in
      the Control group, and significantly increased in the Endotoxemia group at each
      time point. The Glutamine-treated group showed noticeably reduced Bax mRNA
      expression at 2 hrs post-injection while other time points were similar to the
      Control group. The ratio of Bax and Bcl-2 mRNA expression at each time point in
      the Endotoxemia group was significantly higher than that in the Control group
      while the Glutamine-treated group demonstrated significantly lower ratio of Bax
      and Bcl-2 mRNA expression than both. CONCLUSIONS: Glutamine treatment increased
      Bcl-2 mRNA expression and decreased Bax mRNA expression, as a result, the ratio
      of Bax and Bcl-2 mRNA expression decreased. The effects of glutamine resulted in
      a suppression of intestinal epithelial apoptosis and maintained the integrity of
      the gut barrier structure.

PMID- 17178045
TI  - [Wiskott-Aldrich syndrome: A case report and literature review].

PMID- 17178046
TI  - [Clinical analysis of 22 cases of neonatal adrenal hemorrhage].

PMID- 17178047
TI  - [Endocrine alteration was presented as the first symptom of childhood
      intracranial tumor: Clinical analysis of 13 cases].

PMID- 17178048
TI  - [Hematological system abnormalities caused by cytomegalovirus infection].

PMID- 17178049
TI  - [Effectiveness of topiramate in the treatment of childhood migraine].

PMID- 17178050
TI  - [Application of intravenous anesthesia in bronchoscopy in children].

PMID- 17178051
TI  - [Therapeutic effect of continuous blood purification upon critical illness
      children with acute renal failure].

PMID- 17178052
TI  - [Exchange transfusion of blood via peripheral blood vessels for treating neonatal
      hyperbilirubinemia].

PMID- 17178053
TI  - [Catheter interventions for congenital heart disease: The nursing experience of
      1100 cases].

PMID- 17178054
TI  - [Prader-Willi syndrome: A case report].

PMID- 17178055
TI  - [Recent development of resuscitation of newborn infants with asphyxia].

PMID- 17178056
TI  - [Research advance on the mechanism of congenital anomalies caused by folic acid
      deficiency].

PMID- 17178057
TI  - [Hemolytic uremic syndrome].

PMID- 17178059
TI  - [Inoperable valve disease: should percutaneous valve replacement be an option?].
AB  - Surgical valve replacement is the treatment of choice in patients with severe
      valvular heart disease. However, published data clearly show that long-term
      survival is seriously compromised in those with a low inotropic reserve. In
      addition, a growing number of patients (estimated to be around 15% of those with
      aortic stenosis) present in such a poor and deteriorating clinical condition that
      they cannot be accepted for surgery because it involves a very high risk of
      death. Percutaneous balloon valvuloplasty is a less aggressive alternative which
      offers a form of palliative treatment that can increase the patient's life
      expectancy and bring about immediate hemodynamic and clinical improvement. It is
      in this context that the possibility of carrying out percutaneous valve
      replacement has become available as a novel therapeutic option since Cribier
      first reported using the procedure to treat a patient with severe aortic
      stenosis. Since this first operation, both the techniques employed and the
      material composition of the prosthesis have undergone substantial development.
      However, significant problems have been encountered in evaluating the safety and
      efficacy of percutaneous valve replacement. These, to a great extent, stem from
      the risks associated with treating elderly patients who have high morbidity and
      mortality. In the United States, one clinical study was even suspended because
      two of the first four patients undergoing treatment died. In contrast, studies
      carried out in other countries, although they have involved only a few patients,
      have produced more promising results. Moreover, because the cause of death in
      these series was frequently due to factors that were independent of good valvular
      function, the future of the technique is generally thought to be positive.
      Nevertheless, the results obtained with percutaneous mitral valve replacement
      have been poor. In conclusion, the technique of percutaneous valve replacement,
      although still undergoing development, is becoming established as a viable
      alternative for treating inoperable valve disease, at least in aortic valves.

PMID- 17178060
TI  - [Primary prophylaxis with the implantable cardioverter-defibrillator in heart
      failure: a clinical point of view].
AB  - The implantable cardioverter-defibrillator (ICD) is one of the great inventions
      of modern cardiology. Its use for the prevention of sudden death in patients with
      left ventricular dysfunction has meant that clinical cardiologists are now fully
      involved in decision-making on the implantation of these devices. The majority of
      clinical trials, which have used low ejection fraction as the only or main
      criterion for patient recruitment, have shown that ICD use leads to a significant
      improvement in survival. Three trials, two of which were carried out soon after
      myocardial infarction and one of which was performed at the same time as surgical
      revascularization, were exceptions. However, it is important to be aware that the
      improvements observed in the most recent trials have not been as large as those
      seen in the initial studies. Reduced efficacy has meant that in the Sudden
      Cardiac Death in Heart Failure Trial (SCD-HeFT), for instance, 25 ICDs had to be
      implanted to save one life over a 2-year period. The most likely explanation for
      this observation is that the better prognosis achieved by present-day
      pharmacologic treatment of heart failure has reduced the margin of benefit
      associated with ICD use. Another consequence is that depressed left ventricular
      ejection fraction has lost some of its specificity in predicting sudden death.
      New predictive variables are needed to improve risk stratification in this
      population. Without these variables, the use of ICDs in the primary prevention of
      sudden death in patients with left ventricular dysfunction will not seem a very
      attractive option from the point of view of good clinical practice.

PMID- 17178061
TI  - [The importance of fetal echocardiography in the detection and management of
      congenital cardiac malformations].
AB  - Using present-day high-resolution ultrasound scanners, it is possible to
      visualize and study the heart during the different stages of fetal growth in
      patients at risk of some forms of congenital heart disease. Detailed anatomical
      knowledge of cardiac structures combined with the accurate interpretation of
      echocardiographic images made during fetal development enable early diagnosis of
      particular forms of congenital disease that have serious pathophysiologic
      consequences. In addition, it also becomes possible to select the most
      appropriate nature and timing of delivery, and to organize early treatment for
      the newborn. Any decision taken on how to treat a fetus in which a congenital
      cardiac abnormality has been identified must be taken by a multidisciplinary
      team. This will help in coordinating the measures that must be taken after
      delivery and, in the near future, in implementing intrauterine surgery. Fetal
      echocardiography is establishing itself as a valuable tool in the management of
      the various types of congenital malformation, which together comprise the main
      cause of death among the newborn. In addition, the technique can be used to
      confirm and broaden our knowledge of the natural history of cardiac
      malformations, which are the most common congenital malformations. There is no
      doubt that the application and understanding of this imaging technology will
      increase the survival rate of newborns with specific congenital cardiac
      abnormalities, and will have a significant impact on long-term clinical outcome
      and quality of life in these patients.

PMID- 17178062
TI  - [Implementation of clinical guidelines].
AB  - Clinical guidelines play an important supportive role in improving everyday
      clinical practice. Their benefits are beyond doubt because failure to implement
      them is associated with a poorer prognosis. Nevertheless, clinical guidelines
      have their critics and limitations. Simply publishing guidelines does not mean
      that they will be implemented. It is essential, therefore, to understand the
      difficulties that can impede implementation in practice. Both the assessment of
      guideline implementation and the design of programs for improving implementation
      require a specific methodology. Use of this methodology to devise programs that
      encourage the implementation of clinical guidelines has resulted in improved
      adherence to guideline recommendations and, significantly, in a reduction in
      morbidity and mortality.

PMID- 17178063
TI  - [Basic research into asthma: where are we heading?].

PMID- 17178064
TI  - [Long-term outcomes of treatment with bosentan in pulmonary hypertension].
AB  - OBJECTIVE: Treatment with bosentan improves exercise capacity in patients with
      pulmonary hypertension. Few studies have assessed treatment with this drug over
      long periods. The aim was therefore to assess long-term treatment with bosentan.
      PATIENTS AND METHODS: A group of 22 functional class III patients--18 women and 4
      men, mean age, 45.5 years (range, 19-77 years)--with pulmonary hypertension were
      treated with bosentan between April 2002 and June 2005. Pulmonary hypertension
      was idiopathic in 10 patients. In the remaining patients, etiologies were
      associated with compensated heart failure (n = 4), scleroderma (n = 4),
      peripheral embolism (n = 3), and portal hypertension (n = 1). Clinical and
      hemodynamic variables and their changes between baseline and the end of study
      were analyzed. RESULTS: The mean duration of follow-up of the patients was 15.7
      months (range, 12.6-31.8 months). Functional class improved or stabilized after 3
      months of treatment in 21 (95%) and after 1 year in 14 (64%). At 3 months, the
      distance covered in the 6-minute walk test increased by a mean of 64.5 m, an
      improvement that was maintained at 6, 12, and 18 months. Treatment was
      interrupted in 4 patients (18%). Reasons for discontinuation were death in 2
      patients, deterioration in 1 patient, and intolerance of the medication in 1
      patient. Treatment was ineffective for 4 patients (18%). No patient experienced
      notable liver toxicity. CONCLUSIONS: The results of this study suggest that
      treatment with bosentan is associated with long-term improvement in clinical
      variables and exercise capacity in approximately two thirds of the patients with
      pulmonary hypertension.

PMID- 17178065
TI  - [Associations between family history of allergy, exposure to tobacco smoke,
      active smoking, obesity, and asthma in adolescents].
AB  - OBJECTIVE: The relationships between asthma in adolescents and various
      environmental and social exposures needs to be clarified. The aim of this study
      was to determine the association between family history of allergy, passive or
      active tobacco smoking, obesity, and asthma in adolescents. SUBJECTS AND METHODS:
      A population-based case-control study was carried out. A random sample of 4003
      students aged 13 to 18 years old was selected from secondary and preparatory
      schools in an urban area in northeastern Mexico. Data was gathered in physical
      examinations and with a questionnaire administered by trained staff. Two study
      groups were formed: a group of 253 adolescents with asthma and a control group of
      students without asthma. RESULTS: Variables associated with asthma were family
      history of allergy (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.28
      2.06), passive smoking (OR, 1.53; 95% CI, 1.18-1.99), and obesity (OR, 1.96; 95%
      CI, 1.45-2.65). Female gender and active smoking were unrelated to asthma. The
      percentage of obese adolescents was higher in the group of asthmatics (18.2%)
      than in the control group (12.8%). CONCLUSIONS: Family history of allergy,
      passive tobacco smoking, and obesity seem to be the main risk factors for the
      development of asthma in adolescents. The relationship of active smoking and
      asthma requires further study.

PMID- 17178067
TI  - [Trends in lung cancer mortality rates in the provinces of Andalusia, Spain, 1975
      2002].
AB  - OBJECTIVE: To describe trends in lung cancer mortality rates in the different
      provinces of Andalusia, Spain, from 1975 through 2002. MATERIAL AND METHODS:
      Deaths from lung cancer during the period 1975 through 2002 were obtained from
      the Spanish national institute of statistics. Crude rates and age-adjusted rates
      (overall and truncated 35-64 year rates) were calculated. RESULTS: In Andalusia
      in 2002 there were 2802 deaths from lung cancer in men and 254 in women,
      representing 28.4% and 4.5%, respectively, of the mortality rate from tumors.
      Joinpoint regression analysis distinguished 3 recent trends in truncated (range,
      35-64 years) lung cancer mortality rates in men: decrease in Sevilla, increase in
      Huelva and Jaen, and stability in the other provinces. For women there was a
      marked increase (5.2% annually) during the period 1988 through 2002 in Malaga.
      CONCLUSIONS: From a strategic point of view, antismoking strategies should target
      women in the province of Malaga in particular, with the aim of detaining their
      increasing risk for this type of cancer and of preventing avoidable and premature
      deaths among future generations of women.

PMID- 17178066
TI  - [Recording the daily physical activity of COPD patients with an accelerometer: An
      analysis of agreement and repeatability].
AB  - OBJECTIVE: The purpose of this study was to assess the agreement between
      different measurements of mean daily physical activity taken over a week in
      chronic obstructive pulmonary disease (COPD) patients with an accelerometer and
      to analyze the medium-term repeatability of these measurements. PATIENTS AND
      METHODS: The study enrolled 12 healthy control subjects and 23 patients with
      stable COPD (mean [SD] forced expiratory volume in 1 second [FEV1] of 45% [13%]
      of predicted and a ratio of FEV1 to forced vital capacity of 53% [13%]).
      Accelerometer output, measured in vector magnitude units, was recorded in a
      physical activity log for a 1-week period. The results were then analyzed to
      compare output for a conventional recording period (Friday to Sunday) to that for
      2 other periods (Monday to Wednesday and Tuesday to Thursday). The measurements
      were repeated 3 to 5 weeks later. RESULTS: Activity counts were lower in the COPD
      patients than in the control subjects (184 [99] vs 314 [75]; P < .001). In the
      COPD patients, the results for the Friday to Sunday period correlated well with
      the results for both the Monday to Wednesday period (95% confidence interval, 
      29.21 to 28.81) and the Tuesday to Thursday period (95% confidence interval, 
      32.13 to 28.43). There were no significant differences in terms of medium-term
      repeatability of accelerometer readings between the COPD group and the control
      group (repeatability coefficient of 11.2% [4.6%] and 8.5% [4.7%], respectively).
      CONCLUSIONS: Both agreement between the different measurements of physical
      activity taken during a 1-week period and medium-term repeatability for COPD
      patients and control subjects were very good.

PMID- 17178068
TI  - [Use of spirometry in the diagnosis and treatment of chronic obstructive
      pulmonary disease in primary care].
AB  - OBJECTIVE: The aim of this study was to assess the use of spirometry for the
      diagnosis and follow-up of patients with chronic obstructive pulmonary disease
      (COPD) in primary care in terms of deficiencies and the requirements for its
      correct use, and to identify the regimens most commonly used in patients with
      COPD. METHODS: The study included 839 primary care physicians, each of whom
      completed 2 questionnaires, one on treatment of COPD and the other on the use of
      spirometry for diagnosis and follow-up of the disease. RESULTS: Notable among the
      results was the high number of questionnaires in which no response was given to
      the question on classification of patients according to the severity of airway
      obstruction (10.7% of cases) and the low number of correct responses to questions
      on treatment with bronchodilators during the stable phase of COPD (15.1%). The
      highest rate of correct responses was for questions regarding the indication for
      spirometry, all of which were answered correctly in more than 60% of cases. Only
      59.2% of primary health care centers performed spirometry, mainly due to a lack
      of training. In more than 30% of cases the nursing staff had not received
      specific training, a finding that was reflected in the poor compliance with
      guidelines for calibration (10.9% of health care centers performed daily
      calibrations), cleaning of the spirometer (in 13.9% of cases the equipment was
      never cleaned), and providing patients with pretest recommendations (30% did not
      provide recommendations the day before spirometry). CONCLUSIONS: Primary care
      physicians are aware of the usefulness of spirometry for the diagnosis and follow
      up of COPD. Although they are able to recognize airflow obstruction, they do not
      classify patients correctly in terms of severity. Very limited availability of
      spirometry was observed in primary health care centers and there was little
      training in the use of the technique, a finding reflected in the poor compliance
      with guidelines for its use.

PMID- 17178069
TI  - [Guidelines for the diagnosis and management of alpha-1 antitrypsin deficiency].

PMID- 17178070
TI  - [Outpatient management of malignant pleural effusion using a tunneled pleural
      catheter: Preliminary experience].
AB  - Inpatient management of malignant pleural effusion includes the placement of a
      conventional thoracostomy tube for drainage and talc slurry pleurodesis and/or a
      surgical approach consisting of video-assisted thoracoscopic talc insufflation.
      Both techniques require prolonged hospital stays of up to 1 week. Unfortunately,
      life expectancy in patients with this disease does not usually exceed 6 months,
      and so the primary aim of any palliative intervention intended to improve quality
      of life should be to avoid hospital admissions and to relieve pain as far as
      possible. Of the few outpatient alternatives to hospital management the most
      frequently used is repeated thoracentesis. We describe the outpatient management
      of malignant pleural effusion by placement of a tunneled pleural catheter in a
      patient with stage IIIB lung adenocarcinoma. In our opinion, the use of this
      catheter offers a viable alternative to conventional therapy and is better
      tolerated.

PMID- 17178071
TI  - [Pneumonectomy in octogenarian patients].
AB  - Recent decades have witnessed a progressive aging of the population and a
      resulting increase in the numbers of elderly patients seeking health care. Since
      age and pneumonectomy are independent predictors of perioperative morbidity and
      mortality, such surgery is not recommended for octogenarian patients. We report
      the experience of 6 such patients who underwent pneumonectomy for squamous cell
      carcinoma in 5 cases and a typical carcinoid tumor in the sixth. There was no
      perioperative mortality; morbidity and survival rates were acceptable.

PMID- 17178072
TI  - [Financing smoking cessation treatment through national health systems may
      improve success].

PMID- 17178073
TI  - [Quality indicators in Hypertension Care Units: indicators of structure in the
      QUALIHTA study].
AB  - AIM: To evaluate the minimum-required indicators of quality of care in
      Hypertension Units at two levels of delivered care (secondary and tertiary) in
      Spain. METHODS: A total of 51 quality indicators were included (N) in order to
      evaluate: architectural resources (8), material resources (12 on devices and 22
      on supportive services) and human resources (9), which were presented as a
      formulary to the head of the corresponding Hypertension Unit. As a measure of the
      indicator, the accomplishment (yes/no) was registered. RESULTS: Data from 61
      participating centers were collected and included in the analysis: 42 (68,9%)
      centers of tertiary level and 19 (31,1%) of secondary level. The degree of
      compliance of the different quality indicators in the global sample is (range):
      architecture, 60%-100%; material resources, 83.3%-100% (devices); 57.4-100%
      auxiliary services; 51.7% with respect to human resources and 69-100% with
      respect to continuing education and the dedication of the personnel. As expected,
      the differences between care levels were observed mainly in the availability of
      auxiliary services. CONCLUSIONS: The Hypertension Units in Spain comply with a
      series of structural indicators of care quality at an acceptable level. The
      degree of compliance in certain aspects of human resources, mainly percent of
      dedication, number and continuing education could be improved. The evaluation of
      these aspects of care quality could allow the Scientific Societies to define the
      recommendation in order to deliver the best quality of care in hypertension.

PMID- 17178074
TI  - [Place of death of elderly persons in Catalonia].
AB  - STUDY OBJECTIVE: To describe the place of death of the elderly and to analyze the
      factors associated with death occurring in an acute care hospital. DESIGN: Cross
      sectional interview of a randomized sample of individuals aged 65 or over who
      died during the year 1998. Three to four months after the death of the elderly
      subject, the main caregiver was interviewed about the socio-demographic
      characteristics, chronic conditions, functional and cognitive status, and use of
      health services in the months previous to the death, as well as the place where
      death occurred and their preferences on this site. SETTING: Six areas of
      Catalonia, Spain, differing in the level of health and end of life social
      services. PARTICIPANTS: 584 caregivers (78.6% response rate). MAIN RESULTS: Mean
      age of the deceased elderly was 81.4 (+/- 8) and half of them were females. 52%
      (95% CI: 47.5-55.7) had died in acute care hospitals. 35% of the caregivers of
      those dying at an acute hospital reported that they would have preferred another
      place for death. After adjustment, variables associated with dying in acute care
      hospitals were: living in an area with lower availability of social and health
      services for the end of life (OR: 2.8; 95% CI: 1.4-5.5) and suffering from
      chronic obstructive pulmonary disease (OR: 1.7; 95% CI: 1.1-2.5). CONCLUSIONS:
      Acute hospitals are the predominant place of death in Catalonia, Spain. The place
      of death seems to be more closely influenced by the availability of end-of-life
      care services. There is a clear preference for dying at an alternative place to
      acute hospitals.

PMID- 17178075
TI  - [Prevalence of cardiovascular risk factors in HIV-infected patients].
AB  - INTRODUCTION: To determine the prevalence of cardiovascular risk factors in human
      immunodeficiency virus (HIV)-infected patients. PATIENTS AND METHOD: A cross
      sectional study was performed with HIV-infected patients aged 20 or over managed
      at the outpatient Infectious Disease Unit during 2003. Clinical and
      epidemiological characteristics of HIV infection and cardiovascular risk factors
      were evaluated. RESULTS: The final 760 patients included in the study had a mean
      of 1.5 cardiovascular risk factors, with smoking being the most prevalent (66.8%;
      CI 95%: 63.4-70.2). The cardiovascular risk factor of age and gender was present
      in 26.4% (CI 95%: 23.3-29.7) of patients and family history of premature coronary
      heart disease in 14.3% (CI 95%: 11.8-16.9). The prevalence of hypertension and
      diabetes mellitus was 13.2% (CI 95%: 10.8-15.8) and 4.3% (CI 95%: 3.0-6.0),
      respectively. High density lipoprotein (HDL) cholesterol concentration under 40
      mg/dl was found in 29.3% (CI 95%: 26.1-32.7) and above 60 mg/dl in 16.3% (CI 95%:
      13.8-19.1). Twenty-five patients (3.3%; CI 95%: 2.1-4.8) had suffered overt
      cardiovascular disease. CONCLUSION: Smoking and HDL cholesterol were the main
      cardiovascular risk factors in this HIV-infected cohort.

PMID- 17178076
TI  - [Varicella pneumonia in adult population: review of 21 cases].
AB  - BACKGROUND: Retrospective study of the varicella pneumonia in adults, in order to
      know incidence, environmental and clinical characteristics and treatments of
      patients with this diagnosis during the last 9 years in Toledo. MATERIAL AND
      METHODS: Twenty-one adult patients with the diagnosis of varicella pneumonia were
      studied, using the information of clinical histories and codified data. The
      backgrounds of pregnancy, smoking habit, concomitant diseases, previous contacts
      with another patients and the season of the year, were evaluated. Diagnosis was
      established by clinical and radiologic criteria in the course of varicella
      infection. RESULTS: 21 patients (10 males and 11 females, between 25 and 73
      years) were studied. 17 (81%) were smokers, in 15 (71.4%) there was documented
      contact with varicella infection and 4 (19%) were immunocompromised. In the first
      3-7 days after the development of skin lesions (100%), there was fever in 20
      cases (95.2%) and dyspnea in 14 (66.7%). There were 4 patients (33,3%) without
      respiratory symptoms and in 5 (23,8%) there was important hypoxemia. Evolution
      was satisfactory in 20 cases (95.2%); three others requiring admission to
      Intensive Care Unit. Chest X-ray revealed an interstitial pattern in 11 cases
      (52.4%), nodular in 4 (19%) and a mixed pattern in 5 (23.8%). 20 patients were
      treated with acyclovir and in one case with foscarnet. In 28.57% cases,
      corticosteroids were needed. CONCLUSIONS: We believe smoking habit could be a
      risk factor related to an increase of varicella pneumonia. A chest X-ray should
      be made in every patient, despite the symptoms. Adults with pneumonia have a
      better prognosis if acyclovir is started early in time. Concomitant treatment
      with corticosteroids should be used in those cases with respiratory
      insufficiency.

PMID- 17178077
TI  - [New, relevant and practical aspects of the treatment of neuropathic pain].
AB  - In the Spanish population it is difficult to calculate the prevalence of
      neuropathic pain (NP) although it is estimated that it is present in 40% of the
      cases of chronic pain. The treatment is not easy and we must choose between the
      different drugs, the most appropriate taking into account the effectivity in data
      from clinical trials, releaf of comorbidities associated to NP and less side
      effects. In this way, the Finnerup NB's work establishes an algorithm of
      treatment of NP and it is very helpful for clinicians in order to choose the most
      suitable treatment. In this work, the author recommends antiepileptic drugs, like
      gabapentin and pregabalin as first choice treatments. Amitriptiline, a tricycle
      antidepressant and opioids must be used only when there is a lack of response or
      intolerance.

PMID- 17178078
TI  - [Cerebral amyloid angiopathy and dementias].
AB  - Amyloid deposit in the brain causes neurologicaldiseases characterized by
      dementia. These depositsare constituted by fibrilar proteins with beta
      planarshape whose origin is due to mutations, infectionsor exogenous alterations.
      Treatment of cerebralamyloid angiopathy depends on the cause and atpresent, the
      manipulation of the synthesis of theresponsible peptides, their chemical
      solubilizationor extraction outside of the nervous system, arebeing investigated.

PMID- 17178079
TI  - [Diagnosis of metabolic syndrome. Adaptation of diagnostic criteria in our
      setting. Recommendations of the HDL forum].

PMID- 17178080
TI  - [Abdominal pain with very uncommon etiology].

PMID- 17178081
TI  - [55 year old male with stroke and dyspnea].

PMID- 17178082
TI  - [Massive pulmonary thromboembolism associated to peripheral arterial embolism].

PMID- 17178083
TI  - [Anterior hypertrophic cardiomyopathy. Image in magnetic resonance].

PMID- 17178084
TI  - [Fever, dyspnea and bacteriemia due to Klebsiella oxytoca and Enterobacter
      cloacae].

PMID- 17178085
TI  - [Pelvic mass in a patient with background of mycosis fungoid].

PMID- 17178086
TI  - [Is ischemic heart disease in type I myotonic dystrophy really uncommon?].

PMID- 17178087
TI  - [Realities in enteral nutrition approach of our patients].

PMID- 17178088
TI  - [Amiodarone as cause of Periodic thyrotoxic hypopotasemic paralysis].

PMID- 17178089
TI  - [Factor V Leiden and retinal central artery thrombosis].

PMID- 17178090
TI  - [Psychic distress in hospital setting].

PMID- 17178091
TI  - Frequency-doubling perimetry: comparison with standard automated perimetry to
      detect glaucoma.
AB  - PURPOSE: To compare second generation frequency-doubling perimetry (FDP) with
      standard automated perimetry (SAP) to detect glaucomatous visual field
      abnormalities. DESIGN: Prospective, cross-sectional, controlled observational
      study. METHODS: Fifty eyes of 50 patients with glaucoma with confirmed SAP visual
      field abnormalities and 42 eyes from 42 normal control subjects were studied.
      Swedish Interactive Thresholding Algorithm (SITA) standard 24-2 SAP and FDP
      visual fields were performed. The correlation of global indices and the number of
      defects on total deviation (TD) and pattern deviation (PD) plots were compared.
      The spatial concordance of FDP and SAP defect locations was determined. RESULTS:
      In patients with glaucoma, significant correlations of mean deviation (MD) and
      pattern standard deviation (PSD) were found between SAP and FDP (P < .001 for MD
      and P < .001 for PSD), but not in the normal group. FDP had significantly greater
      defect scores than SAP on total deviation and PD plots in the glaucoma group (P =
      .028 and P = .01, respectively). In comparison with SAP, sensitivity and
      specificity of FDP were 92% and 98% with glaucoma hemifield test criteria and 98%
      and 93% with PSD <5% criteria, respectively. Similarly high diagnostic precision
      was found with MD and PSD (at 95% specificity; MD and PSD sensitivity was 82% and
      90%, respectively). The location of defects within 12 hemifield clusters found
      with FDP agreed moderately well with those detected with SAP (kappa = .48).
      CONCLUSIONS: FDP and SAP perform similarly in their ability to detect visual
      field defects in early to moderate glaucoma. Larger and deeper defects detected
      with FDP suggests the possibility of earlier detection at high specificity.

PMID- 17178092
TI  - Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and
      metabolites through electrochemical studies at the interface between two
      immiscible solutions.
AB  - For the first time, the partition coefficients of the ionized forms of several
      opioids, amphetamine-like drugs, and their metabolites were determined by
      studying their ionic transfer process across the bare interface water/organic
      solvent. The ionic partition coefficients of the monocationic forms of 12
      compounds--heroin, 6-monoacetylmorphine (6-MAM), morphine, acetylcodeine,
      codeine, dihydrocodeine, methamphetamine, amphetamine, 3,4
      methylenedioxymethamphetamine (MDMA or "ecstasy"), 3,4-methylenedioxyamphetamine
      (MDA), 3-methoxy-alpha-methyldopamine (3-OMe-alpha-MeDA), and alpha
      methyldopamine (alpha-MeDA)-were attained using electrochemical measurements, by
      cyclic voltammetry, at the interface between two immiscible electrolyte solutions
      (ITIES). Then the acquired lipophilicity values were correlated to the chemical
      structure of the compounds and with the metabolic pathways central to each class
      of drugs. Although the mechanisms of biotoxicity of this type of drugs are still
      unclear, the data obtained evidence that the lipophilicity of metabolites may be
      a contributing factor for the qualitative differences found in their activity. In
      addition, the partition coefficients of the ionic drugs were calculated using
      three available software packages: ModesLab, Dragon, and HyperChem. As shown by
      cross-comparison of the experimental and calculated values, HyperChem was the
      most reliable software for achieving the main goal. The data obtained so far seem
      to be correlated to the proposed metabolic pathways of the drugs and could be of
      great value in understanding their pharmacological and/or toxicological profiles
      at the molecular level. This study may also contribute to gaining an insight into
      the mechanisms of biotransportation of this type of compounds given that the
      ionic partition coefficients reflect their ability to cross the membrane
      barriers.

PMID- 17178093
TI  - Analysis of variable N-glycosylation site occupancy in glycoproteins by liquid
      chromatography electrospray ionization mass spectrometry.

PMID- 17178094
TI  - Pentalenolactone biosynthesis: Molecular cloning and assignment of biochemical
      function to PtlF, a short-chain dehydrogenase from Streptomyces avermitilis, and
      identification of a new biosynthetic intermediate.
AB  - Pentalenolactone (1) is an antibiotic that has been isolated from many species of
      Streptomyces. The putative dehydrogenase encoded by the ptlF gene (SAV2993) found
      within the Streptomyces avermitilis pentalenolactone gene cluster was cloned and
      overexpressed in Escherichia coli. PtlF, which belongs to the short-chain
      dehydrogenase/oxidoreductase superfamily, was shown to catalyze the oxidation of
      1-deoxy-11beta-hydroxypentalenic acid (9) to 1-deoxy-11-oxopentalenic acid (10),
      a new intermediate of the pentalenolactone biosynthetic pathway. The methyl ester
      of 10 was characterized by NMR, GC-MS and high resolution mass spectrometry. PtlF
      exhibited a 150-fold preference for beta-NAD(+) over beta-NADP(+). PtlF had a pH
      optimum of 8.0 in the physiological pH range, while a significant activity
      enhancement was observed from pH 9.0 to 11.3. At pH 8.0, PtlF had a k(cat) of
      0.65+/-0.03 s(-1), with a K(m) for 9 of 6.5+/-1.5 microM and K(m) for NAD(+) of
      25+/-3 microM.

PMID- 17178095
TI  - Kinetic and chemical mechanisms of shikimate dehydrogenase from Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis shikimate dehydrogenase (MtbSD) catalyzes the fourth
      reaction in the shikimate pathway, the NADPH-dependent reduction of 3
      dehydroshikimate. To gather information on the kinetic mechanism, initial
      velocity patterns, product inhibition, and primary deuterium kinetic isotope
      effect studies were performed and the results suggested a steady-state ordered bi
      bi kinetic mechanism. The magnitudes of both primary and solvent kinetic isotope
      effects indicated that the hydride transferred from NADPH and protons transferred
      from the solvent in the catalytic cycle are not significantly rate limiting in
      the overall reaction. Proton inventory analysis indicates that one proton gives
      rise to solvent isotope effects. Multiple isotope effect studies indicate that
      both hydride and proton transfers are concerted. The pH profiles revealed that
      acid/base chemistry takes place in catalysis and substrate binding. The MtbSD 3D
      model was obtained in silico by homology modeling. Kinetic and chemical
      mechanisms for MtbSD are proposed on the basis of experimental data.

PMID- 17178096
TI  - Glycogen synthase binds to sarcoplasmic reticulum and is phosphorylated by CaMKII
      in fast-twitch skeletal muscle.
AB  - We investigated the subcellular localization of glycogen synthase (GS) in the
      adductor muscle of anesthetized rabbits injected intravenously with propranolol.
      Under these experimental conditions, glycogen content was about 10 mmol/kg of
      fresh tissue. Immunofluorescent and fractionation studies showed that GS
      associated with sarcoplasmic reticulum (SR) membranes. Glycogen and GS always co
      sedimented, suggesting a predominant role of glycogen in targeting of GS to SR.
      SR-associated GS was phosphorylated in vitro by SR-bound Ca2+-calmodulin
      dependent protein kinase (CaMKII) and dephosphorylated by endogenous protein
      phosphatase 1 (PP1c). Based on measurements of GS activity ratio, in vitro
      phosphorylation of GS by CaMKII did not significantly affect GS activity per se.
      However, GS activity ratio was slightly reduced, when SR membranes were further
      incubated with ATP after prior phosphorylation by CaMKII, suggesting that CaMKII
      might act sinergistically with other protein kinases. We propose that SR-bound
      CaMKII plays a role in regulation of glycogen metabolism in skeletal muscle, when
      intracellular Ca2+ is raised.

PMID- 17178097
TI  - Role of sphingomyelin and ceramide in the regulation of the activity and fatty
      acid specificity of group V secretory phospholipase A2.
AB  - We previously showed that group V secretory phospholipase A(2) (sPLA(2)V) is
      inhibited by sphingomyelin (SM), but activated by ceramide. Here, we investigated
      the effect of sphingolipid structure on the activity and acyl specificity of
      sPLA(2)V. Degradation of HDL SM to ceramide, but not to ceramide phosphate,
      stimulated the activity by 6-fold, with the release of all unsaturated fatty
      acids being affected equally. Ceramide-enrichment of HDL similarly stimulated the
      release of unsaturated fatty acids. Incorporation of SM into phosphatidylcholine
      (PC) liposomes preferentially inhibited the hydrolysis of 16:0-20:4 PC.
      Conversely, SMase C treatment or ceramide incorporation resulted in preferential
      stimulation of hydrolysis of 16:0-20:4 PC. The presence of a long chain acyl
      group in ceramide was essential for the activation, and long chain
      diacylglycerols were also effective. However, ceramide phosphate was inhibitory.
      These studies show that SM and ceramide in the membranes and lipoproteins not
      only regulate the activity of phospholipases, but also the release of
      arachidonate, the precursor of eicosanoids.

PMID- 17178098
TI  - The effect of saliva composition on texture perception of semi-solids.
AB  - Saliva is expected to be of significance for the perception of food stimuli in
      the mouth. Mixing the food with saliva, including breakdown and dilution, is
      considered to be of large importance for semi-solids as these products are
      masticated without chewing. It is known that there are large variations in
      composition of saliva originating from different glands and different subjects.
      In this study we investigated how variations in salivary characteristics affect
      sensory perception. Eighteen trained subjects participated in the study. Saliva
      was collected at rest and during three types of stimulation (odour, parafilm
      chewing and citric acid), and flow rates were determined. The collected saliva
      was analyzed for protein concentration, buffer capacity, mucin level and alpha
      amylase activity. The salivary components measured in this study varied
      considerably among subjects, but also within subjects as a result of different
      means of stimulation. Variations in salivary components were correlated with
      sensory perception of a number of flavour, mouth feel and after feel attributes
      in the semi-solids mayonnaise and custard dessert. Total protein concentration
      and alpha-amylase activity were observed to correlate most strongly with texture
      perception.

PMID- 17178099
TI  - Interactive relationship between the mechanical properties of food and the human
      response during the first bite.
AB  - Biting is an action that results from interplay between food properties and the
      masticatory system. The mechanical factors of food that cause biting adaptation
      and the recursive effects of modified biting on the mechanical phenomena of food
      are largely unknown. We examined the complex interaction between the bite system
      and the mechanical properties. Nine subjects were each given a cheese sample and
      instructed to bite it once with their molar teeth. An intra-oral bite force-time
      profile was measured using a tactile pressure-measurement system with a sheet
      sensor inserted between the molars. Time, force, and impulse for the first peak
      were specified as intra-oral parameters of the sample fracture. Mechanical
      properties of the samples were also examined using a universal testing machine at
      various test speeds. Besides fracture parameters, initial slope was also
      determined as a mechanical property possibly sensed shortly after bite onset. The
      bite profile was then examined based on the mechanical parameters. Sample
      specific bite velocities were identified as characteristic responses of a human
      bite. A negative correlation was found between bite velocity and initial slope of
      the sample, suggesting that the initial slope is the mechanical factor that
      modifies the consequent bite velocity. The sample-specific bite velocity had
      recursive effects on the following fracture event, such that a slow velocity
      induced a low bite force and high impulse for the intra-oral fracture event. We
      demonstrated that examination of the physiological and mechanical factors during
      the first bite can provide valuable information about the food-oral interaction.

PMID- 17178100
TI  - A review of burst generation by trigeminal main sensory neurons.
AB  - In this paper, we present evidence that neurons in the dorsal part of the
      trigeminal main sensory nucleus participate in the patterning of mastication.
      These neurons have special membrane properties that allow them to generate
      rhythmical bursts of action potentials in the frequency range of natural
      mastication even when cut off from synaptic inputs. These properties mature
      during the third postnatal week in rats at the same time as mastication begins.
      Finally, we present evidence that a reduction on extracellular calcium
      concentration is an important step in the initiation of mastication.

PMID- 17178101
TI  - Orientational polarisability of lipid membrane surfaces.
AB  - Here we present a fluorescence method based on the Stokes shift of the voltage
      sensitive dye di-8-ANEPPS to quantify the orientational polarisability of lipid
      membrane surfaces, i.e. the polarisability due to molecular reorientation. Di-8
      ANEPPS is already an established probe of membrane dipole potential. Its use,
      therefore, as a probe of both the dipole potential and orientational
      polarisability allows a direct comparison of these two properties in an identical
      region of the lipid bilayer. We applied the new technique on phosphatidylcholine
      vesicles to study the effects of different degrees of hydrocarbon saturation and
      of the incorporation of cholesterol and some of its oxidized derivatives. We
      found that lipids with unsaturated chains had a lower orientational
      polarisability than those with saturated chains. This could be explained by a
      reduction in membrane dipole potential as a result of a decrease in lipid packing
      density. Cholesterol derivatives were found to either increase or decrease the
      orientational polarisability depending on their molecular structure. The varying
      effects could be explained by antagonistic effects of the dipole potential and
      membrane order, which are both changed to varying degrees by the cholesterol
      derivatives and which lead to increases and decreases in orientational
      polarisability, respectively.

PMID- 17178102
TI  - Aquaporin-11 containing a divergent NPA motif has normal water channel activity.
AB  - Recently, two novel mammalian aquaporins (AQPs), AQPs 11 and 12, have been
      identified and classified as members of a new AQP subfamily, the "subcellular
      AQPs". In members of this subfamily one of the two asparagine-proline-alanine
      (NPA) motifs, which play a crucial role in selective water conduction, are not
      completely conserved. Mouse AQP11 (mAQP11) was expressed in Sf9 cells and
      purified using the detergent Fos-choline 10. The protein was reconstituted into
      liposomes, which were used for water conduction studies with a stopped-flow
      device. Single water permeability (pf) of AQP11 was measured to be 1.72+/
      0.03x10(-13) cm(3)/s, suggesting that other members of the subfamily with
      incompletely conserved NPA motifs may also function as water channels.

PMID- 17178103
TI  - Inducing an interpretation bias changes self-imagery: a preliminary
      investigation.
AB  - Prior work suggests that variations in self-imagery can influence the emotional
      interpretations people make about social situations. The current experiment
      investigated the converse possibility: that inducing an inferential bias can
      change the content of self-related images. The effects of repeated practice in
      accessing either negative or positive social outcomes was tested by having
      participants report on self-images generated during subsequent experience with
      ambiguous social situations. Participants and independent judges rated the
      content of participants' self-images as being more negative after prior practice
      in accessing negative rather than positive social outcomes. Furthermore,
      participants who practiced accessing negative outcomes rated their anticipated
      anxiety in an imagined stressful social situation as being greater, and their
      expected social performance as poorer than participants in the positive outcome
      group. Groups did not differ in state anxiety levels when making their ratings,
      so it is unlikely that any observed differences between groups can be attributed
      to mood effects. We suggest that this finding is consistent with the hypothesis
      that inferential biases and content of self-images can interact with each other
      and may together serve to maintain social anxiety.

PMID- 17178104
TI  - Simple screening method for differentially methylated regions of the genome using
      a small number of cells.
AB  - Genomic DNA methylation is a major epigenetic mechanism controlling the
      expression of genetic information. Therefore, identifying regions of the genome
      that are differentially methylated in different cells is a useful strategy for
      the study of biological phenomena. To date, several useful screening methods have
      been established for identifying differentially methylated genomic regions.
      However, it is impossible to use these methods in fields of study in which it is
      difficult to obtain a large number of uniform cells, because considerable amounts
      of genomic DNA are required. Given this situation, we developed a method for
      preparing large genomic DNA from a small number of cells, and a simple and highly
      sensitive method for screening for differentially methylated sites. Combined,
      these two methods comprise a simple screening method, which we named
      "Differential Methylation Site Scanning" (DMSS), for identifying differentially
      methylated regions of the genome from a small number of cells. Just 10 cells are
      sufficient for the method described here.

PMID- 17178105
TI  - Characterization of NtChitIV, a class IV chitinase induced by beta-1,3-, 1,6
      glucan elicitor from Alternaria alternata 102: Antagonistic effect of salicylic
      acid and methyl jasmonate on the induction of NtChitIV.
AB  - Tobacco BY-2 class IV chitinases (TBC-1, TBC-3) were rapidly and transiently
      induced by the beta-1,3-, 1,6-glucan elicitor from Alternaria alternata 102
      (AaGlucan). The full-length cDNA and 5'-flanking region of a gene encoding class
      IV chitinases were isolated on the basis of the amino acid sequence of TBC-1.
      Sequence analysis indicated that NtChitIV encoded TBC-1, TBC-3, or both. Since
      purified TBC-1 and TBC-3 from BY-2 cells lack a chitin binding domain in the N
      terminal region, these enzymes suggested to be derived from NtChitIV by post
      translational proteolytic processing. The transcripts of NtChitIV accumulated
      rapidly within 1h after treatment with AaGlucan. Accumulation was maximal 3h
      after treatment. Reporter gene assays were used to analyze the promoter regions
      involved in the transcriptional control of NtChitIV, and these assays revealed
      that the 1.89-kb NtChitIV promoter was activated by AaGlucan but not by salicylic
      acid (SA) or methyl jasmonate (MeJA). The AaGlucan-induced transcriptional
      activation via 1.89-kb NtChitIV promoter was attenuated by pretreatment with SA
      or MeJA. These results suggest that NtChitIV expression is particularly induced
      by AaGlucan and that the AaGlucan-dependent signaling pathway is different from
      the SA- and MeJA-dependent signaling pathways.

PMID- 17178106
TI  - GmDREB2, a soybean DRE-binding transcription factor, conferred drought and high
      salt tolerance in transgenic plants.
AB  - A novel DREB (dehydration responsive element binding protein) homologous gene,
      GmDREB2, was isolated from soybean. Based on its similarity with AP2 domains,
      GmDREB2 was classified into A-5 subgroup in DREB subfamily in AP2/EREBP family.
      Expression of GmDREB2 gene was induced by drought, high salt, and low temperature
      stresses and abscisic acid treatment. The GmDREB2 bound specifically to DRE
      element in vitro. Furthermore, the overexpression of GmDREB2 activated expression
      of downstream genes in transgenic Arabidopsis, resulting in enhanced tolerance to
      drought and high-salt stresses and did not cause growth retardation. Analysis of
      free proline contents in transgenic tobacco indicated that the overexpression of
      GmDREB2 accumulated higher level of free proline compared to the wild type plants
      under drought condition. The results from this study indicate that this novel
      soybean GmDREB2 gene functions as an important transcriptional activator and may
      be useful in improving of plant tolerance to abiotic stresses in plants.

PMID- 17178107
TI  - Adult pancreatic islets require differential pax6 gene dosage.
AB  - Pax6, a paired homeodomain transcription factor, plays crucial roles in
      morphogenesis of eye, central nervous system, and pancreatic islets. Recently,
      heterozygosity for pax6 mutation has been reported in some individuals with
      glucose intolerance and aniridia. To investigate the role of pax6 for pancreatic
      islet function, we examined the pancreatic phenotype of small eye rat strain
      (rSey(2)) with a point mutation in the pax6 locus resulting in truncated PAX6
      proteins. Analyses of the insulin secretory profile of heterozygous rSey(2)/+
      revealed that insulin secretion is significantly increased in response to
      membrane-depolarizing stimuli such as arginine, tolbutamide, and KCl. The
      processes of insulin granule exocytosis were suggested to be enhanced in
      rSey(2)/+. On the other hand, pancreatic insulin and glucagon content and islet
      architecture in rSey(2)/+ showed no significant differences compared to wild
      type. These findings indicate differential requirements for pax6 gene dosage in
      displaying function and maintaining architecture of adult pancreatic islets.

PMID- 17178108
TI  - Iron (III) reduction: A novel activity of the human NAD(P)H:oxidoreductase.
AB  - NAD(P)H:quinone oxidoreductase (NQO1; EC 1.6.99.2) catalyzes a two-electron
      transfer involved in the protection of cells from reactive oxygen species. These
      reactive oxygen species are often generated by the one-electron reduction of
      quinones or quinone analogs. We report here on the previously unreported Fe(III)
      reduction activity of human NQO1. Under steady state conditions with Fe(III)
      citrate, the apparent Michaelis-Menten constant (Km(app)) was approximately 0.3
      nM and the apparent maximum velocity (Vmax(app)) was 16 U mg(-1). Substrate
      inhibition was observed above 5 nM. NADH was the electron donor, Km(app)= 340
      microM and Vmax(app) = 46 Umg(-1). FAD was also a cofactor with a Km(app) of 3.1
      microM and Vmax(app) of 89 U mg(-1). The turnover number for NADH oxidation was
      25 s(-1). Possible physiological roles of the Fe(III) reduction by this enzyme
      are discussed.

PMID- 17178109
TI  - Curcumin enhances cystic fibrosis transmembrane regulator expression by down
      regulating calreticulin.
AB  - Curcumin has been reported to correct cystic fibrosis caused by the DeltaF508
      mutation of the cystic fibrosis transmembrane regulator (CFTR) but its
      mechanistic action remains unclear. We have recently demonstrated that the ER
      chaperone calreticulin (CRT) negatively regulates the CFTR cell surface
      expression and activity. Thus, we aimed at determining whether CRT mediates the
      effect of curcumin on CFTR. We show here that the treatment with curcumin of
      Chinese hamster ovary cells suppressed CRT expression and increased wild-type
      CFTR but did not affect DeltaF508 CFTR expression. However, we determined that
      although curcumin did not augment DeltaF508 CFTR expression, it enhanced the
      functional competence of DeltaF508 CFTR induced by 26 degrees C incubation. Knock
      down of CRT by siRNA at low-temperature had a similar effect. Our findings
      suggest that the positive effect of curcumin on CFTR expression is mediated
      through the down-regulation of CRT, a negative regulator of CFTR.

PMID- 17178110
TI  - Identification of a complement receptor 1 peptide for inhibition of immune
      hemolysis.
AB  - Complement sensitization of red blood cells (RBCs) can cause life-threatening
      hemolytic anemias. We have previously shown that complement receptor 1 (CR1)
      derivatives specifically the N-terminal region with decay accelerating activity
      (DAA) for inactivation of a key enzyme in the complement cascade can reduce
      complement-mediated RBC destruction in vitro and in an in vivo mouse model of
      hemolytic transfusion reaction. In the present study, we have modeled the N
      terminal CR1 molecule based on the X-ray crystal structure of decay accelerating
      factor and the NMR structure of a homologous CR1 domain. Based on the homology
      model, we identified a 34-mer peptide encompassing the putative DAA which in
      vitro reduced hemolysis, C3a release and surface C3 deposition. More importantly,
      this peptide at 0.6 mM was effective in prolonging survival of transfused
      incompatible RBCs in vivo. Our results indicate that CR1-based structure-function
      studies may provide insights for developing structure-derived transfusion
      therapeutics in the future.

PMID- 17178111
TI  - The transport of alpha(1A)-adrenergic receptor with 33-nm step size in live
      cells.
AB  - We used the technique of single particle tracking (SPT) with high tempo-spatial
      resolution to efficiently explore the route and mechanism for the transport of
      alpha(1A)-adrenergic receptor (alpha(1A)-AR) in real time in living cells. We
      found that the initial transport of alpha(1A)-AR in cells depended on actin
      filaments with the velocity of 0.2 microm/s and exhibited discrete 33-nm steps.
      It was noted that the step size, the rate constant, and the velocities were in
      accordance with the character of single myosin in vitro, implying that while
      transporting each endosome myosins did not work in the "tug-of-war" mode and that
      they did not adopt the strategy to boost up transporting speed by working
      coordinately. These results provided insight into the mechanism of GPCR transport
      in vivo.

PMID- 17178114
TI  - Synaptosomal protein synthesis is selectively modulated by learning.
AB  - Synaptosomes from rat brain have long been used to investigate the properties of
      synaptic protein synthesis. Comparable analyses have now been made in adult male
      rats trained for a two-way active avoidance task to examine the hypothesis of its
      direct participation in brain plastic events. Using Ficoll-purified synaptosomes
      from neocortex, hippocampus and cerebellum, our data indicate that the capacity
      of synaptosomal protein synthesis and the specific activity of newly synthesized
      proteins were not different in trained rats in comparison with home-caged control
      rats. On the other hand, the synthesis of two proteins of 66.5 kDa and 87.6 kDa
      separated by SDS-PAGE and analyzed by quantitative densitometry was selectively
      enhanced in trained rats. In addition, the synthesis of the 66.5 kDa protein, but
      not of the 87.6 kDa protein, correlated with avoidances and escapes and inversely
      correlated with freezings in the neocortex, while in the cerebellum it correlated
      with avoidances and escapes. The data demonstrate the participation of synaptic
      protein synthesis in plastic events of behaving rats, and the selective, region
      specific modulation of the synthesis of a synaptic 66.5 kDa protein by the newly
      acquired avoidance response and by the reprogramming of innate neural circuits
      subserving escape and freezing responses.

PMID- 17178112
TI  - Sustained low-grade pro-inflammatory state in unmedicated, remitted women with
      major depressive disorder as evidenced by elevated serum levels of the acute
      phase proteins C-reactive protein and serum amyloid A.
AB  - BACKGROUND: Major depressive disorder (MDD) shows increased coronary artery
      disease (CAD) risk of unknown mechanism(s). MDD is more common in women than men;
      CAD diagnosis can be difficult in women. Elevations of the inflammatory markers C
      reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in
      populations; few data on these markers exist in MDD, particularly in remitted
      patients. METHODS: We measured fasting am serum CRP (high sensitivity, CRP(hs))
      and SAA in 18 unmedicated, remitted women with MDD (mean age 41 +/- (SD)12, body
      mass index (BMI) 25.2 +/- 4.1 kg/m(2)) and 18 BMI-matched healthy control
      subjects (age 36 +/- 10, BMI 25.3 +/- 3.8 kg/m(2)) on 2 separate occasions, > or
      = 6 days apart. RESULTS: Repeat SAA and CRP(hs) measurements strongly correlated
      across study days (SAA: r = .83, p < .001; CRP(hs): r = .94, p < .001). Both SAA
      (5.30 +/- 3.39 vs. 2.84 +/- 1.87 mg/L, p < .005) and CRP(hs) (3.23 +/- 3.17 vs.
      1.12 +/- 1.45 mg/L; p < .01) were significantly elevated in MDD women versus
      controls. CONCLUSIONS: Elevated SAA and CRP(hs) in remitted, unmedicated women
      with MDD indicate a pro-inflammatory state unrelated to current depressive
      symptoms or pharmacotherapy. These findings suggest that inflammatory mechanisms
      may in part underlie findings of increased CAD risk in MDD.

PMID- 17178115
TI  - Semantic re-interpretation and garden path recovery.
AB  - Participant's eye-movements were recorded while they read locally ambiguous
      sentences. Evidence for processing difficulty was found when the interpretation
      of the initially preferred misanalysis clashed with that of the globally correct
      analysis, demonstrating the persistence of the earlier interpretation. Processing
      difficulty associated with the syntactic reanalysis was largely localised to the
      disambiguating region, with difficulty due to semantic persistence occurring
      later. The results show that semantic persistence is not limited to extreme cases
      of parse failure, and can occur even when reanalysis is relatively
      straightforward.

PMID- 17178116
TI  - Cell proliferation drives neural crest cell invasion of the intestine.
AB  - A general mathematical model of cell invasion is developed and validated with an
      experimental system. The model incorporates two basic cell functions: non
      directed (diffusive) motility and proliferation to a carrying capacity limit. The
      model is used here to investigate cell proliferation and motility differences
      along the axis of an invasion wave. Mathematical simulations yield surprising and
      counterintuitive predictions. In this general scenario, cells at the invasive
      front are proliferative and migrate into previously unoccupied tissues while
      those behind the front are essentially nonproliferative and do not directly
      migrate into unoccupied tissues. These differences are not innate to the cells,
      but are a function of proximity to uninvaded tissue. Therefore, proliferation at
      the invading front is the critical mechanism driving apparently directed
      invasion. An appropriate system to experimentally validate these predictions is
      the directional invasion and colonization of the gut by vagal neural crest cells
      that establish the enteric nervous system. An assay using gut organ culture with
      chick-quail grafting is used for this purpose. The experimental results are
      entirely concordant with the mathematical predictions. We conclude that
      proliferation at the wavefront is a key mechanism driving the invasive process.
      This has important implications not just for the neural crest, but for other
      invasion systems such as epidermal wound healing, carcinoma invasion and other
      developmental cell migrations.

PMID- 17178117
TI  - Tvp38, Tvp23, Tvp18 and Tvp15: novel membrane proteins in the Tlg2-containing
      Golgi/endosome compartments of Saccharomyces cerevisiae.
AB  - Four previously uncharacterized proteins (Tvp38, Tvp23, Tvp18 and Tvp15) were
      found in Tlg2-containing membrane by proteomic analysis of immunoisolated Golgi
      subcompartments of Saccharomyces cerevisiae (Inadome et al., Mol. Cell. Biol., 25
      (2005) 7696-7710). Immunofluorescence double staining of HA-tagged Tvp proteins
      and myc-tagged tSNAREs supported that these proteins mainly localize in the Tlg2
      containing compartments. Conserved sequences of Tvp38, Tvp23 and Tvp18 are found
      in higher eukaryotes, but these homologues have not been characterized yet. All
      Tvp proteins were nonessential for growth under laboratory conditions.
      Immunoprecipitation of Tvp proteins indicated that Tvp23, Tvp18 and Tvp15 are in
      an interactive network with Yip1-family proteins, Yip4 and Yip5. They may
      collectively assist in the effective maintenance/function of the late
      Golgi/endosomal compartments. Disruptions of tvp15 and tvp23 showed synthetic
      aggravation with ypt6 or ric1 null mutation. Processing of carboxypeptidase Y and
      alkaline phosphatase in tvp disruptants occurred as in the wild type.

PMID- 17178118
TI  - A study of corneal thickness, shape and collagen organisation in keratoconus
      using videokeratography and X-ray scattering techniques.
AB  - In keratoconus, the cornea becomes progressively ectactic resulting in severe
      visual impairment. Here, we use a combination of videokeratography and
      synchrotron X-ray diffraction to investigate the relationship between corneal
      shape and thickness, and the distribution and predominant orientation of stromal
      fibrillar collagen in five keratoconus corneas. In all but the least advanced
      case, the thinning and ectasia measured in vivo using corneal videokeratography
      was accompanied by corresponding changes in the relative distribution and
      orientation of stromal collagen in the excised corneal buttons. Although the most
      severe case of keratoconus possessed the most pronounced stromal collagen
      alterations, and only a minor disruption to stromal collagen arrangement was seen
      in the least advanced case, a variability in the extent of stromal collagen
      alteration was seen between these clinical extremes. The observed abnormalities
      in collagen distribution and orientation are consistent with a mechanism of
      keratoconus progression that involves inter-fibrillar or inter-lamellar slippage
      causing a redistribution of tissue within the cornea.

PMID- 17178119
TI  - Acetabular fractures in the UK. What are the numbers?
AB  - We have established a nationwide directory of the specialist surgical units and
      their Lead Consultants with expertise in acetabular fracture surgery throughout
      the UK. Our directory has facilitated an estimation of the total numbers of
      operative acetabular fracture cases managed annually in the UK, as reported by
      those actually providing this specialist service. Previously the total number of
      acetabular injuries admitted and operated on in the UK was not known and there
      was no directory of acetabular surgeons in the UK. The introduction and accuracy
      of the OPCS codings will have massive financial implications for the DoH at a
      local and national level in the planning and provision of adequate health care
      resources. We have performed a questionnaire study to validate the DoH data for
      acetabular fracture surgery. Data was compiled using the ICD-10 for diagnosis of
      fracture of the acetabulum, and the OPCS-4 codes for the surgical procedures used
      for fracture fixation for the year 2003-2004. The Department of Health (DoH) data
      identified 44 units that had OPCS-4 coding for acetabular fracture fixation. We
      had a 95% (42 out of 44 units) response to our questionnaire. A total of 9 units
      contacted had actually performed no surgery, whereas the DoH coded these as
      having performed a maximum of 35 cases. The DoH data showed a total of 1825
      admissions to 311 NHS hospitals for acetabular fractures, including 258 operative
      cases performed in 44 NHS hospitals in the UK. Our study has found that 748
      acetabular fracture fixation cases were performed at 33 NHS hospitals in the UK
      in this study period. The total difference between the DoH operated cases and
      those confirmed by our study was 490. The hospital care for an operative
      acetabular fracture case may cost approximately 14,830, pounds if the actual
      numbers are under-reported to or by the DoH are 490, then approximately 7,266,700
      pounds has been lost by these centres due to incorrect proportioning of
      resources.

PMID- 17178120
TI  - The nature and impact of urinary incontinence experienced by patients receiving
      community nursing services: a cross-sectional cohort study.
AB  - BACKGROUND: Nurses have played a pivotal role in the delivery of continence
      services yet little is known about the nature or impact of urinary symptoms
      experienced by patients in receipt of such care. AIM: To define the nature and
      impact of urinary symptoms experienced by patients in receipt of community
      nursing services. METHOD: The Leicestershire Urinary Symptoms Questionnaire was
      administered to 1078 patients with incontinence identified from 176 community
      nurses' caseloads in 157 general practices in England. Information included type
      and severity of urinary symptoms, impact on quality of life, help with coping,
      use of continence products and health service resources. RESULTS: Nine hundred
      and ninety nine (92.7%) patients (median age 79.0 years) returned completed
      questionnaires. Most patients had incontinence between 1 and 5 years duration,
      women were more likely than men to have had long standing ( > 5 years) symptoms
      and more than half the sample reported severe leakage. Women were more likely
      than men to report symptoms of stress incontinence (71.7% and 46.8%,
      respectively, p < 0.001) and urge incontinence UI (86.3% vs. 74.8%, respectively,
      p < 0.01). Half of the men and most women also experienced leakage as a result of
      difficulty getting to, on or off, a toilet/commode. Men were more likely than
      women to report getting up three or more times a night to pass urine (53.6% vs.
      37.0%, respectively, p < 0.05). Most patients reported that their symptoms had a
      significant impact on many aspects of quality of life, and 45.7% would be very
      dissatisfied to continue "the way they are now". Professional help appeared
      principally one of containment. CONCLUSION: Many people with incontinence
      receiving community nursing services experience two or more urinary symptoms
      which, in the majority, have a significant impact on quality of life. Many older
      patients were not satisfied to "put up" with their urinary symptoms. Current
      service provision appears to be failing those who are most in need of such care.

PMID- 17178121
TI  - A novel method for evaluating human carotid artery elasticity: possible detection
      of early stage atherosclerosis in subjects with type 2 diabetes.
AB  - We recently developed a novel method for evaluating the elasticity of arterial
      walls, the phased tracking method. Herein, we evaluated atherosclerosis of the
      carotid artery with this method in 242 individuals with type 2 diabetes. In
      multiple regression analysis of subject status, age, systolic blood pressure and
      hyperlipidemia were found to be independently associated with carotid artery
      elasticity values. We also measured currently established values for
      atherosclerosis, carotid artery IMT and baPWV, in these subjects. Carotid artery
      elasticity correlated with max IMT (r=0.291, p<0.01), plaque score (PS) (r=0.220,
      p<0.01) and baPWV (r=0.345, p<0.01). Elasticity, max IMT and plaque score, all
      correlated with the number of risk factors for atherosclerosis, i.e.
      hypertension, hyperlipidemia and smoking, in addition to diabetes, consistent
      with the view that these values reflect atherosclerosis. Importantly, however, in
      subjects with IMT <1.1mm, who are classified as not having atherosclerosis as
      defined by IMT criteria, only carotid artery elasticity correlated with the
      number of risk factors (p<0.05). These results suggest that (1) the measured
      carotid artery elasticity values reflect atherosclerosis and (2) our novel method
      has potential for detecting atherosclerosis in its early stage.

PMID- 17178122
TI  - Arginine uptake is attenuated, through post-translational regulation of cationic
      amino acid transporter-1, in hyperlipidemic rats.
AB  - Endothelial cell dysfunction (ECD) is a common feature of hypercholesterolemia.
      Defective nitric oxide (NO) generation due to decreased endothelial nitric oxide
      synthase (eNOS) activity is a crucial parameter characterizing ECD. L-arginine is
      the sole precursor for NO biosynthesis. Among several transporters that mediate L
      arginine uptake, cationic amino acid transporter-1 (CAT-1) acts as a specific
      arginine transporter for eNOS. Our hypothesis implies that CAT-1 is a major
      determinant of eNOS activity in hypercholesterolemia. We studied aortic arginine
      uptake, CAT-1 and CAT-2 mRNA expression, and CAT-1, and PKC alpha protein in: (a)
      control, untreated animals (CTL), (b) rats fed with 4% cholesterol+1% cholate and
      2% corn oil for 6 weeks (CHOL) and (c) rats with hypercholesterolemia treated
      orally with either atorvastatin (CHOL+ATORVA, 20mg/kg BW/day) or arginine 1%
      (CHOL+ARG) in the drinking water (modalities which have been shown to enhance CAT
      1 activity and improve endothelial function). Serum cholesterol levels
      significantly increased in cholesterol fed animals, an increase which was blocked
      by atorvastatin (CTL: 66.8+/-15, CHOL: 133.9+/-22, CHOL+ARG: 128.2+/-20,
      CHOL+ATORVA: 77+/-15 mg/dl). Arginine transport was significantly decreased in
      CHOL. Treatment with neither arginine nor atorvastatin had an effect. Using RT
      PCR, we found no change in aortic CAT-1 and CAT-2 mRNA expression in CHOL as well
      as following arginine or atorvastatin administration. The abundance of CAT-1
      protein was significantly augmented in cholesterol fed rats and was not affected
      by arginine or atorvastatin. PKC alpha protein content, which was previously
      shown to regulate CAT-1 activity, increased significantly in CHOL and was neither
      affected by atorvastatin nor arginine. In conclusion, aortic arginine uptake is
      attenuated in hypercholesterolemia, through post-translational modulation of CAT
      1 protein, possibly via upregulation of PKC alpha.

PMID- 17178123
TI  - Association of adiponectin and resistin with cardiovascular events in Korean
      patients with type 2 diabetes: the Korean atherosclerosis study (KAS): a 42-month
      prospective study.
AB  - Adiponectin and resistin are proteins that affect insulin resistance and
      atherosclerosis significantly. We investigated adiponectin and resistin
      concentrations as predictors of cardiovascular events in Korean patients with
      type 2 diabetes. The study in 2001 comprised 343 unrelated patients with type 2
      diabetes (65+/-9.2 years old). They were followed up for 42 months. The baseline
      duration of diabetes, smoking status and history of cardiovascular diseases (CVD)
      were recorded. BMI, blood pressures, HbA1c, lipid profiles, ECG, creatinine and
      urine microalbumin were measured. Adiponectin and resistin were measured using
      enzyme-linked immunosorbent assays. The primary endpoint was defined as one of
      cardiovascular death, myocardial infarct, CABG, stroke, unstable angina or overt
      nephropathy. Thirty-eight patients (11.1%) experienced primary endpoint during
      the follow-up. After adjustment for age, sex, BMI, blood pressure and lipid
      status, participants in the lowest quartile of adiponectin levels compared with
      the highest had significantly increased risk of primary endpoint (relative
      risk=3.03; 95% CI 1.09-8.41; p=0.034). In contrast, resistin level had no
      influence on the risk of primary endpoint. A low level of adiponectin, not
      resistin, was a significant risk factor for the development of cardiovascular
      events in these Korean patients with type 2 diabetes.

PMID- 17178124
TI  - Propylthiouracil, independent of its antithyroid effect, produces endothelium
      dependent vasodilatation through induction of nitric oxide bioactivity.
AB  - OBJECTIVE: Propylthiouracil (PTU), independent of its antithyroid effect, is
      recently found to have a potent antiatherosclerotic effect. The aim of this study
      is to investigate whether PTU has a beneficial effect on endothelial function.
      METHODS AND RESULTS: Ninety patients with a history of hyperthyroidism receiving
      either PTU (n=45) or methimazole (MMI) (n=45) during the euthyroid status were
      enrolled in this study. Brachial artery endothelium-dependent (flow-mediated
      dilatation [FMD]) and endothelium-independent (nitroglycerin-mediated dilatation)
      responses were assessed by high-resolution ultrasound image. Data for these two
      groups were compared with those of 41 healthy control subjects. The FMD values
      were significantly increased in patients maintained on PTU versus those in the
      MMI and control groups (9.3+/-4.4%, 3.4+/-2.5%, and 3.6+/-3.4%, respectively;
      P<0.01). Nitroglycerin-mediated dilatation had no significant difference between
      the PTU, MMI, and control groups (17.4+/-7.5%, 15.9+/-6.1%, and 17.5+/-6.8%,
      respectively; P=0.455). On multivariate analysis, no significant relationship was
      found between the FMD and thyroid hormone index levels. To further elucidate
      whether PTU has a direct effect on endothelial function, the effect of PTU on
      isolated segments of Sprague-Dawley rat aorta was studied. Vasodilatation induced
      by PTU was endothelium-dependent and could be blocked by pretreatment with nitric
      oxide (NO) inhibitors. PTU also increased NO formation in aortic segments.
      CONCLUSIONS: This study demonstrated that PTU produced endothelium-dependent
      vasodilatation through thyroid-independent and NO-mediated mechanisms that may
      contribute to its beneficial effect on atherosclerosis.

PMID- 17178125
TI  - Correlation between severity of sleep apnea and upper airway morphology based on
      advanced anatomical and functional imaging.
AB  - Determination of the apnea hypopnea index (AHI) as a measure of the severity of
      obstructive sleep apnea/hypopnea syndrome (OSAHS) is a widely accepted
      methodology. However, the outcome of such a determination depends on the method
      used, is time consuming and insufficient for prediction of the effect of all
      treatment modalities. For these reasons more methods for evaluating the severity
      of OSAHS, based on different imaging modalities, have been looked into and recent
      studies have shown that anatomical properties determined from three-dimensional
      (3D) computed tomography (CT) images are good markers for the severity of the
      OSAHS. Therefore, we correlated anatomical measurements of a 3D reconstruction of
      the upper airway together with flow simulation results with the severity of OSAHS
      in order to find a combination of variables to indicate the severity of OSAHS in
      patients. The AHI of 20 non-selected, consecutive patients has been determined
      during a polysomnography. All patients also underwent a CT scan from which a 3D
      model of the upper airway geometry was reconstructed. This 3D model was used to
      evaluate the anatomical properties of the upper airway in OSAHS patients as well
      as to perform computational fluid dynamics (CFD) computations to evaluate the
      airflow and resistance of this upper airway. It has been shown that a combination
      of the smallest cross-sectional area and the resistance together with the body
      mass index (BMI) form a set of markers that predict very well the severity of
      OSAHS in patients within this study. We believe that these markers can be used to
      evaluate the outcome of an OSAHS treatment.

PMID- 17178126
TI  - High-performance liquid chromatography: photochemical reduction in aerobic
      conditions for determination of K vitamins using fluorescence detection.
AB  - The development and application of a post-column detection system for K vitamins
      based on their photoreduction to the hydroquinone form is reported. The
      photoreduction yield is practically quantitative and occurs in a PTFE tubing
      coiled around a 6-W low-pressure mercury lamp in the presence of sodium
      dodecylsulfate and methanol. Factors affecting the rate of the photochemical
      reaction were optimised so that its contribution to the total broadening was
      negligible. The enhanced fluorescence and stability of the K vitamins reduced in
      micellar medium has permitted the use of a very sensitive photochemical detection
      system, which can work in aerobic conditions. Separations were carried out by
      reverse-phase chromatography using pure methanol as eluent. The determination of
      phylloquinone, menaquinone-4 and menadione in several real samples illustrates
      the potential of the photochemical detection system.

PMID- 17178127
TI  - Molecularly imprinted solid-phase extraction method for the high-performance
      liquid chromatographic analysis of fungicide pyrimethanil in wine.
AB  - A method for molecularly imprinted solid-phase extraction (MISPE) of the
      fungicide pyrimethanil from wine samples has been investigated. The molecular
      imprinted polymer was obtained by iniferter-mediated grafting on porous
      chloromethylated polystyrene beads, using methacrylic acid as the functional
      monomer and ethylene glycol dimethacrylate as the cross-linker. The imprinted
      beads were evaluated for use as a solid-phase extraction sorbent, in order to
      develop the extraction protocol in aqueous standards and red wine samples. The
      optimised extraction protocol resulted in a reliable MISPE method suitable for
      HPLC analysis (stationary phase: Cromolith Performance C18 column, 100 mm x 4.6
      mm; mobile phase: acetonitrile-water (3:2, v/v), flow-rate: 1.00 ml/min;
      detection 270 nm). It was selective for pyrimethanil and the related pyrimidinic
      fungicides cyprodinil and mepanipyrim, while the non-pyrimidinic fungicides
      benalaxyl, chlozolinate, furalaxyl, iprodione, metalaxyl, nuarimol, procymidone
      and vinclozolin were not extracted. Recoveries performed on a wine matrix spiked
      with pyrimethanil at three different concentration levels were reproducible and
      were in good agreement with the recoveries performed on buffer, coming out
      between 80 and 90% (85+/-7.0% at 0.50 microg/ml, 79+/-1.6% at 2.0 microg/ml and
      87+/-5.6% at 20 microg/ml). Preconcentration and quantitative extraction of
      pyrimethanil from wine samples was shown to be feasible down to 0.1 microg/ml.

PMID- 17178128
TI  - Characterization of ventricular repolarization in male and female guinea pigs.
AB  - Since both components of the delayed rectifier K(+) currents (I(Kr) and I(Ks))
      are present in guinea pig and human ventricle, the guinea pig appears as an
      interesting model to examine the contribution of these currents in sex-related
      difference of cardiac repolarization. Accordingly, we compared ventricular
      repolarization in adult male and female guinea pigs using electrophysiological
      protocols together with Western blots analysis and perfused heart preparation.
      Our results indicate that there was no sex-related difference in the expression
      levels of the different K(+) channels studied (ERG, KvLQT1, minK and Kir2.1), nor
      in the density of the K(+) currents (I(Kr), I(Ks) and I(K1)) encoded by these
      channels. Action potential durations and QTc intervals were also similar between
      males and females. In addition, we compared QTc intervals using Langendorff
      perfused whole hearts in the presence of I(Kr) and/or I(Ks) blockers. The I(Kr)
      blocker (5 microM E-4031) prolonged QTc intervals to a similar extent in male
      (24+/-2%) and female (29+/-3%, p=0.1) hearts. Similarly, the degree of QTc
      prolongation induced by 0.1 microM HMR1556 (I(Ks) blocker) was similar in both
      sexes (males: 15+/-2% and females 18+/-2%; p=0.2). In addition to their QT
      prolonging effects, the I(Kr) and I(Ks) blockers significantly reduced heart rate
      in both male and female guinea pigs. These studies clearly demonstrate that adult
      guinea pigs do not display sex differences in ventricular repolarization.

PMID- 17178130
TI  - Effect of stem cell turnover rates on protection against cancer and aging.
AB  - Tissue stem cells are responsible for replenishing and maintaining a population
      of cells which make up a functioning organ. They divide by asymmetric cell
      division where one daughter remains a stem cell while the other daughter becomes
      a transit cell, which divides a defined number of times and differentiates. A
      fully differentiated cell has a finite life-span. A tissue can be maintained by
      various strategies. Stem cells can divide often and differentiated cells die
      often (fast turnover). Alternatively, stem cells can divide infrequently, and the
      differentiated cells are long lived (slow turnover). Genetic alterations and
      mutations can interfere with tissue homoeostasis. Mutations can induce senescence
      and apoptosis, and this can result in a reduction of the number of functioning
      tissue cells which could correlate with tissue aging. Alternatively, mutations
      can result in the carcinogenic transformation of cells and the formation of a
      tumour. Using mathematical models, I find that the cellular turnover rate affects
      the ability of genetic alterations to induce aging and the development of cancer.
      If mutations occur as a result of errors during cell division, the model suggests
      that a low cellular turnover rate protects both against aging and the development
      of cancer. On the other hand, if mutations occur independent from cell division
      (e.g. if DNA is hit by damaging agents), I find that a high cellular turnover
      rate protects against aging, while it promotes the development of cancer.
      Implications for optimal tissue design are discussed.

PMID- 17178129
TI  - Structure and dynamics of UDP-glucose pyrophosphorylase from Arabidopsis thaliana
      with bound UDP-glucose and UTP.
AB  - The structure of the UDP-glucose pyrophosphorylase encoded by Arabidopsis
      thaliana gene At3g03250 has been solved to a nominal resolution of 1.86
      Angstroms. In addition, the structure has been solved in the presence of the
      substrates/products UTP and UDP-glucose to nominal resolutions of 1.64 Angstroms
      and 1.85 Angstroms. The three structures revealed a catalytic domain similar to
      that of other nucleotidyl-glucose pyrophosphorylases with a carboxy-terminal beta
      helix domain in a unique orientation. Conformational changes are observed between
      the native and substrate-bound complexes. The nucleotide-binding loop and the
      carboxy-terminal domain, including the suspected catalytically important Lys360,
      move in and out of the active site in a concerted fashion. TLS refinement was
      employed initially to model conformational heterogeneity in the UDP-glucose
      complex followed by the use of multiconformer refinement for the entire molecule.
      Normal mode analysis generated atomic displacement predictions in good agreement
      in magnitude and direction with the observed conformational changes and
      anisotropic displacement parameters generated by TLS refinement. The structures
      and the observed dynamic changes provide insight into the ordered mechanism of
      this enzyme and previously described oligomerization effects on catalytic
      activity.

PMID- 17178131
TI  - Intelligent ship traffic monitoring for oil spill prevention: risk based decision
      support building on AIS.
AB  - The paper describes a model, which estimates the risk levels of individual crude
      oil tankers. The intended use of the model, which is ready for trial
      implementation at The Norwegian Coastal Administrations new Vardo VTS (Vessel
      Traffic Service) centre, is to facilitate the comparison of ships and to support
      a risk based decision on which ships to focus attention on. For a VTS operator,
      tasked with monitoring hundreds of ships, this is a valuable decision support
      tool. The model answers the question, "Which ships are likely to produce an oil
      spill accident, and how much is it likely to spill?".

PMID- 17178132
TI  - Dopamine D1 receptor coupling to Gs/olf and Gq in rat striatum and cortex: a
      scintillation proximity assay (SPA)/antibody-capture characterization of
      benzazepine agonists.
AB  - Cloned, human dopamine D(1) receptors recruit multiple effectors but the G
      protein subtype(s) activated by cerebral populations remain poorly defined, a
      question addressed using a rapid immunocapture technique. In rat striatum,
      dopamine (DA) and four selective, benzazepine agonists at D(1) receptors
      concentration-dependently enhanced [(35)S]GTPgammaS binding to Galphas/olf. For
      all drugs, Galphaq was also recruited with similar potencies and efficacies.
      Comparable observations were made in the cortex wherein profiles of Galphas/olf
      vs Galphaq activation were also highly correlated. In contrast to Galphas/olf and
      Galphaq, Galphao and Galphai were activated neither in the striatum nor in the
      cortex, except for SKF82958. As compared to DA, both SKF81297 and SKF82958 were
      full agonists at Gs/olf and Gq in cortex and striatum, whereas SKF38393 behaved
      as a partial agonist. Likewise, the "atypical" agonist, SKF83959 only partially
      activated Galphaq and also Gs/olf in these two regions. In both striatum and
      cortex, the selective D(1) receptor antagonist, SCH23390, abolished the
      recruitment of Galphaq and Galphas by DA, and the action of DA was partially
      attenuated by SKF83959. These findings demonstrate that, in native CNS tissue, DA
      and other D(1) receptor agonists activate Galphas and Galphaq with similar
      potencies and efficacies, suggesting their recruitment via pharmacologically
      indistinguishable populations of D(1) receptors, and show that SPA technology is
      well-adapted to study the coupling of native DA receptors.

PMID- 17178133
TI  - Environmental, seasonal, and social modulations of basal activity in a weakly
      electric fish.
AB  - The electric organ discharge (EOD) of weakly electric fish encodes information
      about species, sex, behavioral, and physiological states throughout the lifetime.
      Its central command is crucial for sensory-motor coordination, and is therefore
      the target of plastic mechanisms that adapt fish to environmental and social
      challenges. The EOD waveform of Brachyhypopomus pinnicaudatus is modulated by
      environmental factors and the neuroendocrine system. In this study we investigate
      the effects of water temperature and day-night cycle upon EOD rate in this
      species during the breeding and non-breeding seasons. During the non-breeding
      season, EOD rate is a linear function of water temperature and exhibits
      counterclockwise hysteresis. During breeding, a thermal resistance strategy
      prevents the decrease of EOD rate to cooling. A nocturnal increase of EOD basal
      rate independent of water temperature and locomotor activity was demonstrated in
      isolated non-breeding adults and in male-female dyads all year round. An
      additional increase of nocturnal EOD rate, probably acting as a social courtship
      signal, was found in breeding dyads. This additional increase of nocturnal EOD
      rate could not be fully explained by gonadal maturation and was modulated by
      social stimuli. This study provides novel data on the complex interactions
      between environment, reproductive cycle, social behavior, and electromotor output
      in an advantageous model of the vertebrate central nervous system.

PMID- 17178134
TI  - "Some guys have all the luck": mate preference influences paced-mating behavior
      in female rats.
AB  - In the present study, mating behavior was observed in female rats that were given
      the opportunity to mate with two males simultaneously. Three groups of females
      were tested: 1) sexually naive, naturally cycling rats in proestrous; 2) sexually
      naive, hormone-primed, ovariectomized (OVX) rats; and 3) hormone-primed, OVX rats
      tested 1 week after sexual receptivity testing. One male rat was determined to be
      the preferred male for each female, if she spent more time with him during a
      mating test. Independent of sexual experience, female rats were less likely to
      leave their preferred male than their non-preferred male following intromissions.
      However, when they left their preferred male, they returned to him faster than to
      their non-preferred male. This effect of preference was slightly more robust in
      the OVX rats. When female rats from Group 2 were tested with the same pair of
      males for 3 additional tests, each female's preference for a particular male was
      stable. That is, a female rat preferred the same male in approximately 3 out of
      the 4 tests, which is more likely than would be expected by chance. In a final
      experiment, pairs of male rats were tested with different females once weekly to
      determine if different females would prefer particular males consistently.
      Although no male rat was preferred by all females, females consistently preferred
      the same male from each pair during approximately 70% of the tests. In
      conclusion, female mate preference may have adaptive significance for the
      reproductive success of rats.

PMID- 17178135
TI  - The effects of individual housing on 'anxious' behaviour in male and female
      gerbils.
AB  - Gerbils are social animals and live in family groups in the wild, suggesting that
      individual housing may be a psychosocial stressor in this species. In the present
      study, gerbils were housed in same sex groups for 4 weeks, and then were either
      individually housed or remained with their cage mates for 1 week. Gerbils were
      tested in the black/white box (BWB), elevated plus maze (EPM) and social
      interaction test. Results indicated no significant differences in behaviour in
      the BWB. In contrast, on the EPM individually housed males showed increased
      anxiety compared to other groups, whilst there were no specific effects in
      females. In the social interaction test, however, individual housing in males
      increased social investigation, whilst females showed a decrease in exploration,
      accompanied by increased immobility. Passive immobility (freezing) was also
      increased in both sexes following individual housing. Thus, data from the EPM
      suggest that individual housing leads to increased anxiety mainly in males,
      whilst data from the SI suggests broadly the opposite. Therefore, individual
      housing results in different behavioural changes in male and female gerbils,
      which are dependent upon the test situation. This study highlights two key
      points. Firstly, it is important to use our knowledge of the species natural
      ecology in interpreting and designing anxiety tests. Secondly, it is important to
      assess behaviour in a range of situations when attempting to measure 'anxiety',
      particularly where tests developed for use in one species/sex are being used in
      another.

PMID- 17178136
TI  - The shape of things to come?

PMID- 17178137
TI  - The burden of HIV and AIDS on blood bank reserves in northeast Nigeria.
AB  - This study was conducted to evaluate the burden of HIV/AIDS on blood bank
      reserves at the University of Maiduguri Teaching Hospital, Nigeria, during 1995
      2005. The number of admissions due to HIV/AIDS rose from 43 in 1995 to 447 in
      2005, and the proportion of blood units used in transfusing patients with
      HIV/AIDS rose steadily from 3% in 1995 to 19% in 2005. The proportion of blood
      units used in managing obstetric patients was also high and fluctuated between
      36% and 50% during the period of study. Controlling the spread of HIV, effective
      treatment of patients with antiretroviral drugs and setting up a functional
      national blood transfusion service could lessen the rising burden of transfusion
      in Nigeria and improve blood availability for maternal and child health care.

PMID- 17178139
TI  - Wagner's canalization model.
AB  - Wagner (1996, Does evolutionary plasticity evolve? Evolution 50, 1008-1023.) and
      Siegal and Bergman, 2002 and Azevedo et al., 2006 have studied a simple model of
      the evolution of a network of N genes, in order to explain the observed
      phenomenon that systems evolve to be robust. These authors primarily considered
      the case N=10 and used simulations to reach their conclusions. Here we
      investigate this model in more detail, considering systems of different sizes
      with and without recombination, and with selection for convergence instead of to
      a specified limit. For the simpler evolutionary model lacking recombination, we
      analyze the system as a neutral network. This allows us to describe the
      equilibrium distribution networks within genotype space. Our results show that,
      given a sufficiently large population size, the qualitative observation that
      systems evolve to be robust, is itself robust, as it does not depend on the
      details of the model. In simple terms, robust systems have more viable offspring,
      so the evolution of robustness is merely selection for increased fecundity, an
      observation that is well known in the theory of neutral networks.

PMID- 17178138
TI  - G beta gamma signaling reduces intracellular cAMP to promote meiotic progression
      in mouse oocytes.
AB  - In nearly every vertebrate species, elevated intracellular cAMP maintains oocytes
      in prophase I of meiosis. Prior to ovulation, gonadotropins trigger various intra
      ovarian processes, including the breakdown of gap junctions, the activation of
      EGF receptors, and the secretion of steroids. These events in turn decrease
      intracellular cAMP levels in select oocytes to allow meiotic progression, or
      maturation, to resume. Studies suggest that cAMP levels are kept elevated in
      resting oocytes by constitutive G protein signaling, and that the drop in
      intracellular cAMP that accompanies maturation may be due in part to attenuation
      of this inhibitory G protein-mediated signaling. Interestingly, one of these G
      protein regulators of meiotic arrest is the Galpha(s) protein, which stimulates
      adenylyl cyclase to raise intracellular cAMP in two important animal models of
      oocyte development: Xenopus leavis frogs and mice. In addition to G(alpha)(s),
      constitutive Gbetagamma activity similarly stimulates adenylyl cyclase to raise
      cAMP and prevent maturation in Xenopus oocytes; however, the role of Gbetagamma
      in regulating meiosis in mouse oocytes has not been examined. Here we show that
      Gbetagamma does not contribute to the maintenance of murine oocyte meiotic
      arrest. In fact, contrary to observations in frog oocytes, Gbetagamma signaling
      in mouse oocytes reduces cAMP and promotes oocyte maturation, suggesting that
      Gbetagamma might in fact play a positive role in promoting oocyte maturation.
      These observations emphasize that, while many general concepts and components of
      meiotic regulation are conserved from frogs to mice, specific differences exist
      that may lead to important insights regarding ovarian development in vertebrates.

PMID- 17178140
TI  - Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?
AB  - Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase
      insecticide, parathion. We determined the effects of parathion on brain nitric
      oxide and its possible role in potentiation of toxicity by glucose feeding. Adult
      rats were given water or 15% glucose in water for 3 days and challenged with
      vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose
      and brain cholinesterase, citrulline (an indicator of nitric oxide production)
      and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose
      feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15
      33%) and decreased cortical cholinesterase activity (81-90%), with no significant
      differences between water and glucose treatment groups. In contrast, parathion
      increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats
      drinking water, with significantly greater changes in glucose-fed rats (248-363%
      increase and 31-61% decrease, respectively). We then studied the effects of
      inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30
      mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co
      exposure to parathion and 7NI led to a marked increase in cholinergic signs of
      toxicity and lethality, regardless of glucose intake. Thus, glucose feeding
      enhanced the accumulation of brain nitric oxide following parathion exposure, but
      inhibition of nitric oxide synthesis was ineffective at counteracting increased
      parathion toxicity associated with glucose feeding. Evidence is therefore
      presented to suggest that nitric oxide may play both toxic and protective roles
      in cholinergic toxicity, and its precise contribution to modulation by glucose
      feeding requires further investigation.

PMID- 17178142
TI  - Perceptual learning without signal.
AB  - Perceptual learning is characterized by an improvement in a perceptual task
      following practice. Several studies have demonstrated that top-down processes,
      such as attention and task-related expectations, can be necessary components of
      perceptual learning [Ahissar & Hochstein, 1993, 2000, 2002; Fahle & Morgan, 1996;
      Seitz, Lefebvre, Watanabe, & Jolicoeur, 2005; Seitz, Nanez, Holloway, Koyama, &
      Watanabe, 2005; Seitz & Watanabe, 2003; Shiu & Pashler, 1992]. Here, we report an
      experiment that isolated top-down processes in perceptual learning, using a
      variant of the Gosselin and Schyns (1992) no-signal procedure. Results indicate
      that top-down processes can be sufficient to produce substantial, possibly long
      lasting and rotation-invariant perceptual learning.

PMID- 17178141
TI  - A mouse cell-adapted NS4B mutation attenuates West Nile virus RNA synthesis.
AB  - An adaptive mutation (E249G) within West Nile virus (WNV) NS4B gene was
      consistently recovered from replicon RNAs in C3H/He mouse cells. The E249G is
      located at the C-terminal tail of NS4B predicted to be on the cytoplasmic side of
      the endoplasmic reticulum membrane. The E249G substitution reduced replicon RNA
      synthesis. Compared with the wild-type NS4B, the E249G mutant protein exhibited a
      similar efficiency in evasion of interferon-beta response. Recombinant E249G
      virus exhibited smaller plaques, slower growth kinetics, and lower RNA synthesis
      than the wild-type virus in a host-dependent manner, with the greatest difference
      in rodent cells (C3H/He and BHK-21) and the least difference in mosquito cells
      (C3/36). Selection of revertants of E249G virus identified a second site mutation
      at residue 246, which could compensate for the low replication phenotype in cell
      culture. These results demonstrate that distinct residues within the C-terminal
      tail of flavivirus NS4B are critical for viral replication.

PMID- 17178143
TI  - Evaluating shape after-effects with radial frequency patterns.
AB  - Mechanisms selective for complex shape are vulnerable to adaptation techniques
      historically used to probe those underlying performance in lower-level visual
      tasks. We explored the nature of these shape after-effects using radial frequency
      patterns. Adapting to a radial frequency pattern resulted in a strong and
      systematic after-effect of a pattern that was 180 degrees out of phase with the
      adapting pattern. This after-effect was characterized as both a shift in the
      point of subjective equality and an increase in response uncertainty. The after
      effect transferred across adapting pattern contrast and adaptor amplitude,
      suggesting an involvement from shape-specific mechanisms located at higher
      processing stages along the visual pathway. Moreover, our results suggested that
      the shift in the point of subjective equality was guided by global processing
      mechanisms, whereas the increase in uncertainty reflected activity from local
      processing mechanisms. Together, these results suggest that shape-specific after
      effects reflect gain control processes at various stages of processing along the
      ventral pathway.

PMID- 17178144
TI  - Localization of visual targets during optokinetic eye movements.
AB  - We investigated localization of brief visual targets during reflexive eye
      movements (optokinetic nystagmus). Subjects mislocalized these targets in the
      direction of the slow eye movement. This error decreased shortly before a saccade
      and temporarily increased afterwards. The pattern of mislocalization differs
      markedly from mislocalization during voluntary eye movements in the presence of
      visual references, but (spatially) resembles mislocalization during voluntary eye
      movements in darkness. Because neither reflexive eye movements nor voluntary eye
      movements in darkness have explicit (visual) goals, these data support the view
      that visual goals support perceptual stability as an important link between pre-
      and post-saccadic scenes.

PMID- 17178145
TI  - Gender differentials of abdominal obesity among the adults in the district of
      Colombo, Sri Lanka.
AB  - OBJECTIVE: To assess the gender-specific prevalence and determinants of abdominal
      obesity (AO) within the population and lifestyle diversity of an urban district
      in Sri Lanka. METHODS: Prevalence of AO (defined by waist circumference) was
      estimated in a cross-sectional study of 1400 adults aged 20-64, residing in the
      district of Colombo in 2004. Demographic, socio-economic and lifestyle factors
      were assessed in gender-specific logistic regression models to identify
      determinants of AO. RESULTS: Prevalence of AO was 44.7% (95% confidence interval
      (CI): 41.0, 48.5) in females and 25.7% (95% CI: 22.6, 29.0) in males. Significant
      determinants of AO were age 35-49 (adjusted odds ratio: 1.7; 95% CI: 1.2, 2.5),
      moderately urban sector (1.9; 1.3, 2.9) and insufficient level of physical
      activity (1.7; 1.1, 2.4) among females in contrast to household income >Rupees
      10,000 (6.1; 2.7, 13.5), increased alcohol (medium: 1.9; 1.2, 2.9; high: 2.1;
      1.2, 3.5), low-fiber diet (1.6; 1.1, 2.4) and frequent large meals (1.7; 1.0,
      2.8) among males. Determinants common to males (M) and females (F) were age
      >or=50 years (M: 2.5; 1.5, 4.2 and F: 2.9; 1.9, 4.4), most urban sector (M: 2.0;
      1.3, 3.1 and F: 1.8; 1.2, 2.7) and married status (M: 2.2; 1.3, 3.6 and F: 2.4;
      1.6, 3.6). CONCLUSIONS: A distinct gender differential was observed in the
      prevalence and determinants of AO. It appears vital that preventive strategies of
      AO be developed to be more 'gender-sensitive' in urban districts.

PMID- 17178146
TI  - The effect of a progesterone releasing intravaginal device (PRID) on pregnancy
      risk to fixed-time insemination following diagnosis of non-pregnancy in dairy
      cows.
AB  - The objective was to compare the probability of pregnancy after fixed-time
      insemination in cows diagnosed as non-pregnant and re-inseminated following the
      Ovsynch protocol, with or without exogenous progesterone. Cows (n=415) used in
      this study originated from 25 farms. Upon diagnosis of non-pregnancy between 30
      and 60 days after AI, cows were randomly assigned to receive either a
      progesterone releasing intravaginal device (PRID; n=208) or a placebo
      intravaginal device (PID; n=207). All cows received GnRH at enrollment (Day 0),
      PGF(2alpha) concurrent with intravaginal device removal 7 days later, GnRH on Day
      9 and fixed-time insemination 16h later (Day 10). Cows observed in estrus prior
      to Day 7, had the device removed and were inseminated. Ovaries were examined by
      transrectal palpation at the time of enrollment and the prominent structures were
      assessed and recorded. Body condition score, lameness status, interval from
      previous insemination, and times bred at enrollment were recorded. At
      intravaginal device removal, the occurrence and intensity of vaginitis was
      determined according to the amount of debris on the device. Overall, the
      intravaginal device retention rate was 91%. A total of 5.2% of PID-treated cows
      and 2.9% of PRID-treated cows were detected in estrus within the 7 days treatment
      period. Pregnancy status was diagnosed between 30 and 56 days after insemination
      and all cows were followed for a minimum of 150 days after enrollment.
      Approximately 28% of cows had evidence of mild vaginitis in response to the
      intravaginal device, whereas 6% of cows had copious debris associated with the
      intravaginal device at removal. The probability of pregnancy after fixed-time
      insemination was 43.8% versus 34.9% in PRID-treated versus PID-treated animals.
      Exogenous progesterone provided through an intravaginal device to non-pregnant
      cows that had not displayed estrus improved the probability of pregnancy after
      fixed-time AI.

PMID- 17178147
TI  - Ultrasonographic image attributes of non-ovulatory follicles and follicles with
      different luteal outcomes in gonadotropin-releasing hormone (GnRH)-treated
      anestrous ewes.
AB  - Ultrasonographic images are composed of multiple square picture elements called
      pixels. Quantitative changes in numerical pixel values (echotexture) determined
      by computer-assisted analysis of digital images reflect discrete changes in the
      microscopic structure and physiological status of ovarian antral follicles. The
      objective of the present study was to determine and compare the ultrasonographic
      attributes of non-ovulatory antral follicles that grew to an ostensibly ovulatory
      diameter (> or =5mm) and follicles with different luteal outcomes in response to
      gonadotropin-releasing hormone (GnRH) in anestrous Western White Face ewes
      (n=34). All animals received GnRH injections (250ng i.v. every 2h for 24h)
      followed by a bolus injection of 125microg of GnRH i.v. Ovarian images obtained
      by repeated transrectal ultrasonography were digitized and subjected to
      computerized analyses to determine the changes in follicular size and echotexture
      of the follicular antrum and wall. At the beginning of GnRH treatment, follicles
      that formed inadequate corpora lutea following ovulation (ICL; n=22) had higher
      (P<0.001) pixel intensity of the central and peripheral antrum compared with non
      ovulatory follicles (n=40). Pixel intensity of the central follicular antrum was
      greater (P<0.01) in follicles that formed ICL compared with follicles that formed
      normal (full-lifespan) CL post-treatment (NCL; n=20) and mean pixel heterogeneity
      of the follicular wall was greater (P<0.05) in non-ovulatory follicles compared
      with follicles that gave rise to NCL. At the time of GnRH bolus injection (i.e.,
      induction of a synchronous LH surge), the mean diameter of non-ovulatory
      follicles was greater (P<0.01) than that of all ovulating follicles, and pixel
      heterogeneity of the central follicular antrum was lowest (P<0.05) in non
      ovulatory follicles. The mean diameter of luteinized unovulated follicles (n=9)
      tended to be greater (P<0.10) at 2.5 and 3 days after emergence, and pixel
      intensity of the follicular wall was lower (P<0.05) compared with non-luteinized
      follicles (n=8) at 1.5 and 2.5 days after emergence (beginning of the growth from
      approximately 3mm onwards). In conclusion, ovarian antral follicles with
      different outcomes after GnRH treatment (in seasonally anestrous ewes) had
      distinctive ultrasonographic characteristics.

PMID- 17178148
TI  - Evaluation of a cushioned method for centrifugation and processing for freezing
      boar semen.
AB  - The purpose of this investigation was to evaluate the use of an iodixanol cushion
      during centrifugation on sperm recovery and yield after centrifugation (sperm
      recovery, sperm motility, viability, membrane lipid disorder, acrosome reaction
      and ROS generation); and to investigate how this procedure affects sperm function
      after freezing-thawing (sperm motility, membrane lipid disorder, acrosomal status
      and homologous in vitro penetration test). The sperm-rich fractions from fertile
      boars were centrifuged under two centrifugation regimes: 800xg for 10min
      (standard method) and 1000xg for 20min with an iodixanol (60% w/v) cushion at the
      bottom of the centrifuge tubes (Cushion method). The highest recovery was
      achieved using the cushion method (sperm loss for cushion method was 0.50%+/-0.18
      versus 2.97%+/-0.43 for standard method, P<0.01) and sperm quality was not
      significantly affected by the centrifugation regime. The motion parameters (%
      progressive motility, % motility, VCL, VSL, VAP, ALH, BCF, P<0.05) of frozen
      thawed samples showed higher values using the standard method. However, a higher
      number of viable spermatozoa with lower lipid disorders were found in spermatozoa
      processed with the cushion method. The in vitro penetration assay showed that the
      individual boar influenced the parameters studied but there were no differences
      between the two centrifugation regimes used. Our results support the hypothesis
      that the proportion of sperm loss in frozen-thawed semen was significantly
      influenced by the centrifugation regime. Therefore, the iodixanol cushion method
      is a suitable tool for cryopreservation of boar semen in order to reduce sperm
      loss without affecting sperm quality.

PMID- 17178149
TI  - Influence of additives on the properties of Bis-GMA/Bis-GMA analog comonomers and
      corresponding copolymers.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of two
      additives: propionaldehyde (aldehyde) and 2,3-butanedione (diketone) on the
      properties of Bis-GMA diluted with TEGDMA and the synthesized Bis-GMA analogs,
      propoxylated Bis-GMA (CH(3)Bis-GMA) and propoxylated fluorinated Bis-GMA
      (CF(3)Bis-GMA). METHODS: Nine experimental comonomers were prepared combining Bis
      GMA and TEGDMA, CH(3)Bis-GMA, CF(3)Bis-GMA, with aldehyde (32mol%) and diketone
      (32mol%). Photopolymerization was effected by using Camphorquinone (0.2wt%) and
      N,N-dimethyl-p-toluidine (0.2wt%). Experimental comonomer viscosity (Brookfield
      viscometer), polymerization shrinkage (gravimetrically), degree of conversion (FT
      IR) and contact angles (contact angle goniometer) were determined. Comonomer and
      copolymer T(g)s (DSC and Fox equation) were also evaluated. Data were analyzed by
      one-way ANOVA and Tukey test (alpha=0.05). RESULTS: Bis-GMA/CH(3)Bis-GMA and Bis
      GMA/CF(3)Bis-GMA with additives exhibited lower viscosities (p<0.01). Inclusion
      of additives into the comonomer systems did not produce significant increase in
      polymerization shrinkage (p>0.05). A significant increase in degree of conversion
      was shown for Bis-GMA/TEGDMA and Bis-GMA/CH(3)Bis-GMA with additives (p<0.01).
      Additives reduced contact angle and comonomer T(g) values, whereas the
      corresponding copolymers with additives showed an increase in T(g). SIGNIFICANCE:
      Use of novel comonomer systems with the addition of aldehyde and diketone
      functional groups would improve dental resin composite properties.

PMID- 17178150
TI  - Micro-XRD study of beta-titanium wires and infrared soldered joints.
AB  - OBJECTIVE: The purpose of this study was to investigate the metallurgical phases
      in beta-titanium soldered joints prepared by infrared soldering, using the Micro
      X-ray diffraction technique (Micro-XRD), and to characterize the Vickers hardness
      in the soldered beta-titanium wires. METHODS: Beta-titanium wires with cross
      section dimensions of 0.032in.x0.032in. (TMA, Ormco), and both titanium-based
      solder (Ti-30Ni-20Cu, Selec) and silver-based solder (Ag-22Cu-17Zn-5Sn, Tomy)
      were selected. Soldering was performed using infrared radiation (RS-1, Morita)
      under argon atmosphere. Micro-XRD analyses were performed at room temperature.
      Micro-XRD spectra were obtained for the boundary region of the soldered beta
      titanium wires using 50microm and 10microm diameter analysis regions. Hardness
      was measured at 30microm intervals from boundary of the diffusion layer and beta
      titanium wire. The Kruskal-Wallis test with the Bonferroni and Wilcoxson Mann
      Whitney tests for nonparametric means were employed as statistical methods
      (P<0.05). RESULTS: For both types of soldered beta-titanium samples, the Micro
      XRD spectra contained four major peaks for body-centered cubic (bcc) beta
      titanium. Additional peaks at about 41 and 45 degrees are attributed to Cu-Ti
      intermetallic phase(s), which may be metastable under soldering conditions. The
      diffusion layer had greater hardness than bulk beta-titanium for both types of
      soldered specimens (P<0.05). SIGNIFICANCE: Soldering of beta-titanium orthodontic
      wire by infrared radiation may be acceptable for clinical use, since Micro-XRD
      spectra revealed that both types of soldered specimens largely retained the bcc
      beta-titanium structure. Further research is needed to investigate the mechanical
      properties and corrosion behavior of infrared-soldered beta-titanium wire.

PMID- 17178151
TI  - Comparison of the color of natural teeth measured by a colorimeter and Shade
      Vision System.
AB  - OBJECTIVES: The objectives were to measure the difference in the color and color
      parameters of natural teeth measured by a tristimulus colorimeter (CM, used as a
      reference) and Shade Vision System (SV), and to determine the influence of color
      parameters on the color difference between the values measured by two
      instruments. METHOD: Color of 12 maxillary and mandibular anterior teeth was
      measured by CM and SV for 47 volunteers (number of teeth=564). Color parameters
      such as CIE L*, a* and b* values, chroma and hue angle measured by two
      instruments were compared. Chroma was calculated as C*ab=(a*2 = b*2)1/2, and hue
      angle was calculated as h degrees =arctan(b*/a*). The influence of color
      parameters measured by CM on the color difference (DeltaE*(ab)) between the
      values measured by two instruments was analyzed with multiple regression analysis
      (alpha=0.01). RESULTS: Mean DeltaE*(ab) value between the values measured by two
      instruments was 21.7 (+/-3.7), and the mean difference in lightness (CIE L*) and
      chroma was 16.2 (+/-3.9) and 13.2 (+/-3.0), respectively. Difference in hue angle
      was high as 132.7 (+/-53.3) degrees . Except for the hue angle, all the color
      parameters showed significant correlations and the coefficient of determination
      (r(2)) was in the range of 0.089-0.478. Based on multiple regression analysis,
      the standardized partial correlation coefficient (beta) of the included
      predictors for the color difference was -0.710 for CIE L* and -0.300 for C*(ab)
      (p<0.01). CONCLUSION: All the color parameters showed significant but weak
      correlations except for hue angle. When lightness and chroma of teeth were high,
      color difference between the values measured by two instruments was small.
      Clinical accuracy of two instruments should be investigated further.

PMID- 17178153
TI  - Brief report: effect of menarcheal status and family structure on depressive
      symptoms and emotional/behavioural problems in young adolescent girls.
AB  - The study investigated the relationship between depressive symptoms and
      emotional/behavioural problems in adolescent girls (N=553) aged 12-13 years,
      menarcheal status and family structure, and considered whether the effect of
      family structure was the same in the presence or absence of menses. The
      Children's Depression Inventory (CDI) and the Strengths and Difficulties
      Questionnaire (SDQ) were administered to a representative sample of adolescents.
      Results showed main effects of menarcheal status and family structure on SDQ
      scores and a significant interaction on CDI scores only. A non-intact family
      appeared to be a stronger risk factor for depressive symptomatology than for
      emotional/behavioural problems in menarcheal girls.

PMID- 17178152
TI  - Preservation of microelastic properties of dentin and tooth enamel in vitro--a
      scanning acoustic microscopy study.
AB  - OBJECTIVES: The aim of this study was to examine the influence of storage media
      on the elastic properties of dentin and tooth enamel with respect to the storage
      period. Several reports suggest that saline and other aqueous solutions may
      induce chemical reactions and the dissolution of minerals, which in turn may
      cause alterations of elastic tissue properties. METHODS: Three non-erupted human
      wisdom teeth were extracted and divided in three slices. Sections were stored in
      three different media for a maximum period of 21 days. During this time all
      sections were inspected by time-resolved 50-MHz scanning acoustic microscopy.
      RESULTS: Storage in saline solution resulted in a progressive decrease of the
      acoustic impedance up to 70% in dentin but not in enamel tissue. Hank's balanced
      salts solution and artificial saliva appeared to maintain the elastic properties
      of dentin and enamel during the entire time of storage. The measurements of
      surface wave velocities did not show significant differences. High resolution
      (900 MHz) inspection of sections cut perpendicular to the surface exposed to the
      storage media for 21 days revealed a progressive increase of impedance in dentin
      up to the initial values at a depth of approximately 300 microm. SIGNIFICANCE:
      These findings suggest that quantitative SAM is a suitable tool for assessing
      surface and sub-superficial elastic properties of tooth tissue.

PMID- 17178154
TI  - Reinforcement sensitivity, coping, and delinquent behaviour in adolescents.
AB  - Since 1964, the relationship between personality and criminal behaviour has been
      extensively studied. However, studies, which have examined the Eysenckian
      dimensions of extraversion, neuroticism and psychoticism have produced mixed
      results. Gray's [Gray, J. A. (1970). The psychophysiological basis of
      introversion-extroversion. Behavior Research and Therapy, 8, 249-266]
      Reinforcement Sensitivity Theory provides an alternative conceptualisation of the
      role of personality in criminal behaviour, and has generally produced more
      consistent findings. This study aimed to examine the relationship between
      reinforcement sensitivity and delinquent behaviour in a sample of 259
      adolescents, and to examine the role that coping strategies play in this
      relationship. Hierarchical regression analyses revealed that use of problem
      solving mediated the relationship between reward sensitivity and delinquent
      behaviour, while use of non-productive coping strategies moderated the
      relationship between BAS drive and delinquency. Consequently, it was suggested
      that coping skills training could be an effective early intervention for
      delinquent behaviour.

PMID- 17178155
TI  - Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10)
      on human monocyte-macrophages in vitro.
AB  - Ferumoxtran-10, a dextran-coated ultrasmall superparamagnetic iron oxide
      particle, has the potential to reveal macrophages in vivo using magnetic
      resonance imaging potentially acting as a marker of inflammatory status. Pending
      clinical trials, we examined the interactions of Ferumoxtran-10 with human
      monocyte-macrophages (HMMs) in vitro to assess its safety and lack of pro
      inflammatory activity. After 72 h, Ferumoxtran-10 was not toxic at 1 mg/ml and
      may be only mildly toxic at 10 mg/ml. Viability in cells with a high
      intracellular Ferumoxtran-10 load was not affected over 14 days. Ferumoxtran-10
      did not interfere with baseline or stimulated cytokine (interleukin-12,
      interleukin-6, tumour necrosis factor-alpha or interleukin-1beta) or superoxide
      anion production or with Fc-receptor-mediated phagocytosis. Similarly,
      Ferumoxtran-10 did not induce cytokine production and was not chemotactic. High
      resolution electron microscopy and selected-area electron diffraction confirmed
      the core of Ferumoxtran-10 is composed of crystalline magnetite. Bright field
      transmission electron microscopy of thin sections demonstrated that Ferumoxtran
      10 was retained in lysosomes of HMM for several days. Ferumoxtran-10 is not toxic
      to HMMs in vitro, does not activate them to produce pro-inflammatory cytokines or
      superoxide anions, is not chemotactic and does not interfere with Fc-receptor
      mediated phagocytosis. Furthermore, extremely high intracellular Ferumoxtran-10
      concentrations had only slight or no effects on these key activities.

PMID- 17178156
TI  - Computational modelling of cell spreading and tissue regeneration in porous
      scaffolds.
AB  - Improved biological and mechanical functionality of musculoskeletal tissue
      engineered constructs is required for clinical application, which can only be
      achieved by comprehensive multidisciplinary research. This review focuses on the
      contribution of computational modelling as a framework for obtaining an
      integrated understanding of key processes, which include: nutrient transport and
      utilization, matrix formation, cell population dynamics, cell attachment and
      migration, and local cell-cell interactions. Such an integrated perspective of
      these key aspects will be critical to open up new directions in tissue
      engineering research, as significant progress can be made by combining existing
      computational and experimental methods. Furthermore, theoretical modelling has
      enormous potential in applications ranging from the interpretation of
      experimental results and the identification of the main governing processes, to
      the optimization of practical tissue engineering protocols with implications
      therein for an increasing ageing population.

PMID- 17178158
TI  - Vitrification as a prospect for cryopreservation of tissue-engineered constructs.
AB  - Cryopreservation plays a significant function in tissue banking and will presume
      yet larger value when more and more tissue-engineered products will routinely
      enter the clinical arena. The most common concept underlying tissue engineering
      is to combine a scaffold (cellular solids) or matrix (hydrogels) with living
      cells to form a tissue-engineered construct (TEC) to promote the repair and
      regeneration of tissues. The scaffold and matrix are expected to support cell
      colonization, migration, growth and differentiation, and to guide the development
      of the required tissue. The promises of tissue engineering, however, depend on
      the ability to physically distribute the products to patients in need. For this
      reason, the ability to cryogenically preserve not only cells, but also TECs, and
      one day even whole laboratory-produced organs, may be indispensable.
      Cryopreservation can be achieved by conventional freezing and vitrification (ice
      free cryopreservation). In this publication we try to define the needs versus the
      desires of vitrifying TECs, with particular emphasis on the cryoprotectant
      properties, suitable materials and morphology. It is concluded that the formation
      of ice, through both direct and indirect effects, is probably fundamental to
      these difficulties, and this is why vitrification seems to be the most promising
      modality of cryopreservation.

PMID- 17178157
TI  - Selective control of liver and kidney cells migration during organotypic
      cocultures inside fibronectin-coated rectangular silicone microchannels.
AB  - In this work, the behaviors of embryonic liver and kidney explants were studied
      inside rectangular polydimethylsiloxane (PDMS) microchannels. The organs were
      cultured under monoculture and coculture conditions on PDMS coated with or
      without fibronectin. The results demonstrated that the migration of cells from
      both organs is dependent on culture conditions and thus can be selectively
      controlled. In liver monocultures without fibronectin, cell migration in the
      microchannels resulted in the formation of a dense 3D tissue. Fibronectin reduced
      liver cell migration and enhanced the emergence of cells demonstrating typical
      hepatocyte phenotypes at the vicinity of the explant. The migration rate in liver
      liver cocultures, with and without fibronectin, was roughly twice the rate of
      cells under monoculture conditions. In cocultures, both livers merged to form a
      large tissue in which the two initial organs could not be identified. In kidney
      monocultures, with and without fibronectin, we did not observe any migration
      inside the microchannels. Contrary to liver cells, kidney cell migration was
      triggered when both fibronectin coating and coculture with liver or another
      kidney explant were used. The migration was more largely observed in coculture
      with liver when compared to kidney-kidney cocultures. In the case of liver-kidney
      coculture with fibronectin, the progression of the kidney cells inside the
      microchannels appears as a displacement of the entire kidney explant in the
      direction of the liver. The liver cells did not move in those cases. After
      contact, we observed a complete merging of both liver and kidney explants. In
      contrast, for liver-kidney cocultures without fibronectin, only the liver moved
      toward the kidney.

PMID- 17178159
TI  - Reduced elimination of Methotrexate in an adult with trisomy 21 and acute
      lymphoblastic leukaemia.

PMID- 17178160
TI  - Degradation of xenobiotics originating from the textile preparation, dyeing, and
      finishing industry using ozonation and advanced oxidation.
AB  - Effluents from textile preparation, dyeing, and finishing processes contain high
      concentrations of biologically difficult-to-degrade or even inert auxiliaries.
      Under these circumstances, it most often becomes inevitable to apply energy
      intense and hence "imperative" treatment technologies (so-called advanced
      oxidation processes, AOPs) to achieve an acceptable reduction in the organic
      content of the effluent, thereby improving the biocompatibility of the originally
      refractory wastewater. The present experimental study focused on three
      problematic dyehouse effluent streams in order to alleviate the problem of
      toxicity and recalcitrance arising from the use of certain textile chemicals at
      source. For that purpose, the textile preparation stage was simulated by a
      nonionic surfactant (NS), the polyamide dyeing stage by a synthetic tannin
      (syntan; ST), and an aqueous biocidal finishing (BF) solution was employed to
      mimic typical textile finishing effluent. Synthetic effluent streams bearing NS,
      ST, or BF were subjected to treatment with different, well-established AOPs
      (ozonation at varying pH; advanced oxidation with H(2)O(2)/UV-C at varying
      H(2)O(2) concentrations) in order to degrade the active ingredients of the
      auxiliary formulations, thereby eliminating their toxicity and recalcitrance.
      Baseline experiments were conducted in order to optimize AOP conditions that were
      consecutively applied to observe changes in the originally poor effluent
      biodegradability and high toxicity. Obtained experimental findings revealed that
      (i) the COD content of NS could be reduced by at least 50% after H(2)O(2)/UV-C
      treatment at pH 9.0 accompanied by a nearly twofold improvement in its already
      fair biodegradability; (ii) the inhibitory effect of the biochemically reluctant
      ST on heterotrophic biomass was completely eliminated upon ozonation (dose=900 mg
      h(-1)) at pH 3.5; and (iii) the microbial toxicity exerted by BF totally
      disappeared after ozonation (dose=600 mg h(-1)) at pH 7.2. However, the
      achievement of detoxification and/or biodegradability improvement was accompanied
      with high electrical energy requirements.

PMID- 17178162
TI  - Expression of Toll-like receptors, interleukin 8, macrophage migration inhibitory
      factor, and osteopontin in tissues from pigs challenged with Salmonella enterica
      serovar Typhimurium or serovar Choleraesuis.
AB  - Two serovars of Salmonella enterica, namely serovar Typhimurium (ST) and serovar
      Choleraesuis (SC) account for the vast majority of clinical cases of swine
      salmonellosis worldwide. These serovars are thought to be transmitted among pigs
      in production settings mainly through fecal-oral routes. Yet, few studies have
      evaluated effects of these serovars on expression of innate immune targets when
      presented to pigs via repeated oral dosing in an attempt to model transmission in
      production settings. Thus, a primary objective of the current experiments was to
      evaluate expression of Toll-like receptors (TLR) and selected chemoattractive
      mediators (interleukin 8, IL8; macrophage migration inhibitory factor, MIF;
      osteopontin, OPN) in tissues from pigs exposed to ST or SC that had been
      transformed with kanamycin resistance and green (STG) or red (SCR) fluorescent
      protein to facilitate isolation from pen fecal samples. In vitro studies
      confirmed that STG and SCR largely (though not completely) retained their ability
      to upregulate IL8 and CC chemokine ligand 20 (CCL20) in cultured swine jejunal
      epithelial cells. Transformed bacteria were then fed to pigs in an in vivo study
      to determine tissue specific effects on mRNA relative expression. Pigs were fed
      cookie dough inoculated with bacteria on days 0, 3, 7, and 10 with 10(8)CFU STG
      (n=8) or SCR (n=8), while control (CTL) pigs (n=8) received dough without
      bacteria. Animals were sacrificed 14 days from the initial bacterial challenge
      and samples of tonsil, jejunum, ileum, colon, mesenteric lymph node (MLN),
      spleen, and liver were removed for subsequent RNA isolation. Expression of mRNA
      in tissues was determined using real-time quantitative PCR and expressed relative
      to 18S rRNA. Within CTL pigs, when expressed relative to the content in liver,
      mRNA for all targets demonstrated substantial tissue effects (P<0.001 for all
      TLR; MIF, and OPN; P<0.05 for IL8). Feeding STG and SCR resulted in significant
      (P<or=0.05) tissue specific effects for TLR5, TLR9, IL8, MIF and OPN. However,
      aside from STG stimulated increase in IL8 in MLN (approximately 10-fold increase
      relative to CTL; P<0.05), significant changes in other molecular targets were
      generally less than one-fold. Results suggest that transformed bacteria may be
      useful in modeling chronic oral exposure of pigs to economically important
      salmonellae serovars. However, although statistically significant effects of
      bacterial feeding were observed in selected tissues for some targets, most
      changes in mRNA were generally incremental in magnitude.

PMID- 17178161
TI  - Gelsolin overexpression alters actin dynamics and tyrosine phosphorylation of
      lipid raft-associated proteins in Jurkat T cells.
AB  - Upon T cell receptor engagement, both the actin cytoskeleton and substrates of
      tyrosine phosphorylation are remodeled to create a signaling complex at the
      interface of the antigen-presenting cell and responding T cell. While T cell
      signaling has been shown to regulate actin reorganization, the mechanisms by
      which changes in actin dynamics affect early T cell signaling have not been fully
      explored. Using gelsolin, an actin-binding protein with capping and severing
      activities, and latrunculin, an actin-depolymerizing agent, we have further
      investigated the interplay between actin dynamics and the regulation of T cell
      signaling. Overexpression of gelsolin altered actin dynamics in Jurkat T cells,
      and alteration of actin dynamics correlated with dysregulation of tyrosine
      phosphorylation of raft-associated substrates. This perturbation of tyrosine
      phosphorylation was correlated with inhibition of activation-dependent signaling
      pathways regulating Erk-1/2 phosphorylation, NF-AT transcriptional activation and
      IL-2 production. Modification of actin by the depolymerizing agent latrunculin
      also altered the tyrosine phosphorylation patterns of proteins associated with
      lipid rafts, and pre-treatment with latrunculin inhibited anti-CD3 mAb-mediated
      NF-AT activation. Thus, our data indicate that actin cytoskeletal dynamics
      modulate the tyrosine phosphorylation of raft-associated proteins and subsequent
      downstream signal transduction.

PMID- 17178163
TI  - Reinstatement of conditioned fear and the hippocampus: an attentional-associative
      model.
AB  - An existing attentional-associative model of classical conditioning [Schmajuk N,
      Lam Y, Gray JA. Latent inhibition: a neural network approach. J Exp Psychol: Anim
      Behav Process 1996;22:321-49] is applied to the description of reinstatement in
      animals and humans. According to the model, inhibitory associations between the
      context (CX) and unconditioned stimulus (US) are formed during extinction, which
      help preserve the association between the conditioned stimulus (CS) and the US.
      However, summation and retardation tests fail to reveal these associations
      because (a) the CX is not attended or (b) a CX-CS configural stimulus formed
      during extinction is both poorly attended and weakly active during testing. When
      US presentations and testing occur in the same context, reinstatement is the
      consequence of a decreased CX inhibition and the increased attention to the CS,
      which activates the remaining CS-US association. When US presentations occur in
      the context of extinction but the CS is tested in a different context,
      reinstatement results from an increased attention to the CS and the combination
      of CS-CX and CX-US excitatory associations. The assumption that associations
      between CSs are impaired following neurotoxic hippocampal lesions or in amnesia,
      is sufficient to describe absence of reinstatement in those cases. However,
      additional assumptions might be needed to describe the effect of hippocampal
      lesions on other postextinction manipulations.

PMID- 17178164
TI  - SINE elements of Entamoeba dispar.
AB  - Entamoeba histolytica and E. dispar are closely related protozoan parasites; the
      former causes clinical amoebiasis in humans while the latter appears to be non
      pathogenic. The molecular biology of E. histolytica shows a number of unusual
      features, one of which is the abundance of polyadenylated but apparently
      untranslatable mRNAs produced; many of these are the product of at least three
      families of SINEs (EhSINE1-3). Here we show that the genome of E. dispar contains
      numerous copies of a SINE element (EdSINE1) whose 5'- and 3'-ends are very
      similar to those of EhSINE1 but with a much less similar middle portion. Twelve
      out of 18 copies examined had target site duplications. In none out of six cases
      examined was there a SINE element in the homologous region of the E. histolytica
      genome but a single copy of EdSINE1 is present in E. histolytica where it is
      identified as EhSINE3.

PMID- 17178166
TI  - Selection of a phage-displayed peptide recognized by monoclonal antibody directed
      blocking the site of hepatitis C virus E2 for human CD81.
AB  - The human CD81 (hCD81) molecule has been identified as a putative receptor for
      hepatitis C virus (HCV). HCV envelope glycoprotein 2 (E2) most likely plays a
      pivotal role in binding to host cells by interacting with the hCD81 molecule. In
      this study, a phage-displayed peptide library was used to select small peptides
      with anti-hCD81 monoclonal antibody JS-81. The output/input ratio of phages
      increased about 91 fold after the third round of selection. Eight of the 30 phage
      clones selected from the phage library showed specific binding to the anti-hCD81
      by enzyme linked immunosorbent assay (ELISA). Competitive inhibition test further
      demonstrated that HCV E2 could significantly inhibit the binding of a positive
      phage clone to anti-hCD81 JS-81. Exogenous small peptide ATWVCGPCT contained by
      the positive phage clones showed aligned with the hCD81 sequence from 153-161 by
      sequence analyses. These results suggest that the selected ATWVCGPCT is a novel
      hCD81-like small peptide, which can block the binding site of HCV E2 for hCD81.
      It may be of further application on development of antiviral agents targeting the
      stage of HCV entry.

PMID- 17178165
TI  - Expression and upregulation of cathepsin S and other early molecules required for
      antigen presentation in activated hepatic stellate cells upon IFN-gamma
      treatment.
AB  - Hepatic stellate cells (HSCs) have been shown to be able to activate T-cells and
      upregulate expression of surface molecules essential for this process, when
      treated with IFN-gamma. But little is known about the early molecules expressed
      by activated hepatic stellate cells under the same treatment. In this study, we
      investigate the effect of IFN-gamma on the transcription and expression of these
      early molecules in hepatic stellate cells. We show on the molecular level that
      activated rat hepatic stellate cells express the class II transactivator, the
      invariant chain (CD74), the MHC class II molecules, as well as cathepsin S, all
      of which are known to be responsible for the initial steps of successful antigen
      presentation. The mRNA and the protein expression level of these molecules is
      upregulated by IFN-gamma. Importantly, IFN-gamma increases cathepsin S activity,
      suggesting a possible involvement of this protease in CD74 processing. Our data
      also show that not only can the HSCs take up antigenic proteins, they can also
      process them. Our comparative study indicates that the rat HSC-T6 cell line
      displays sufficient similarity to the activated rat HSCs in order to serve as a
      model for in vitro studies on the molecular mechanisms of inflammatory response.

PMID- 17178167
TI  - Iteration of high-frequency stimulation enhances long-lasting excitatory
      responses in the spinal dorsal horn of rats: characterization by optical imaging
      of signal propagation.
AB  - To investigate plastic changes in nociceptive sensitivity of the dorsal horn,
      slow excitatory responses elicited by iteration of high-frequency stimulation
      were spatiotemporally observed in spinal cord slices of young-adult rats using
      membrane excitation imaging techniques. Single-pulse stimulation to the dorsal
      root elicited membrane excitation in lamina II, and high-frequency pulse-train
      stimulation evoked long-lasting excitation that expanded widely in the dorsal
      horn. Iteration of high-frequency stimulation enhanced the strength and extent of
      the excitatory responses, but such augmentation of the excitatory responses
      disappeared in the presence of an NMDA receptor antagonist (CPP) and was hindered
      by an NK1 receptor antagonist (L-703.606). The results suggest that activation of
      both NMDA and NK1 receptors is involved in the enhancement of slow excitatory
      responses evoked by iteration of high-frequency stimulation.

PMID- 17178168
TI  - Sight-threatening retinopathy is associated with lower mortality in type 2
      diabetic subjects: a 10-year observation study.
AB  - AIMS: To study associations between diabetic retinopathy and development of
      stroke, myocardial infarction and death in type 2 diabetic patients. METHODS:
      During a 10-year observation period, 363 type 2 diabetic patients (diagnosis > or
      =30 years of age) attending an outpatient clinic were studied regarding the
      prevalence and incidence of retinopathy and associated risk factors, i.e.,
      (HbA(1c), blood pressure, albuminuria, plasma creatinine, age, sex and diabetes
      duration) in relation to the development of myocardial infarction, stroke and
      death. The degree of retinopathy was classified as no retinopathy, background or
      sight-threatening retinopathy, i.e., clinically significant macular edema, severe
      non-proliferative or proliferative retinopathy. RESULTS: During the study period,
      62 patients had had myocardial infarction, 54 stroke and 99 patients died.
      Patients with sight-threatening retinopathy at baseline (n=41) had a 2.2-fold
      increased (p<0.01) risk for death compared to patients with no or background
      retinopathy, even when controlled for medical risk factors. When adjusted for
      medical risk factors, patients with no retinopathy at baseline (n=226) who
      remained without retinopathy or developed background retinopathy (n=187) during
      the study period, had a 3.6-fold increased risk for death (95% CI, 1.1, 11.8),
      (p=0.03), compared to patients who developed sight-threatening retinopathy
      (n=39), while the incidence of myocardial infarction did not differ. More
      patients who developed sight-threatening retinopathy were treated with ACE
      inhibitors than patients who did not (41% versus 24%; p=0.03). CONCLUSION:
      Despite more medical risk factors, patients who developed sight-threatening
      retinopathy had lower mortality compared to patients with no or background
      retinopathy at follow-up. More patients who developed sight-threatening
      retinopathy were treated with ACE inhibitors but this seemed not to have
      influenced the lower mortality rate in this group, whereas the use of ACE
      inhibitors in patients who did not develop sight-threatening retinopathy was
      connected with lower mortality rate.

PMID- 17178169
TI  - A drastic reduction in DOF1 transcript levels does not affect C4-specific gene
      expression in maize.
AB  - The transcription factor DOF1 has been suggested to regulate photosynthetic gene
      expression in maize. By screening a RescueMu transposon-tagged mutant library, we
      identified a maize mutant with a transposon integration in the Dof1 gene 16 bp
      upstream of the transcription initiation site (TIS). Sequencing of the Dof1
      promoter region revealed an unusual promoter structure missing any typical
      elements. Homozygous (ho) mutant lines were generated by selfing and subsequent
      PCR and DNA gel blot analyses. The transposon integration reduced Dof1 transcript
      levels to less than 20% compared to the wild-type and overlapping RT-PCR systems
      revealed that these transcripts were not initiated from the native transcription
      start site. Dof1 transcripts transiently accumulate in wild-type plants after
      illumination of darkened seedlings, but this accumulation cannot be observed in
      mutant lines. However, the time-course of transcript accumulation from the C(4)
      specific phosphoenolpyruvate carboxylase (PEPC) gene, a possible target of DOF1,
      is not altered. Moreover, no impact on the steady-state levels of five additional
      transcripts involved in C(4)-metabolism can be observed. The contents of amino
      acids, glucose, and malate as well as the carbon to nitrogen ratio in the leaves
      remained unchanged when comparing wild-type and mutant plants. Our data question
      the importance of DOF1 in the control of photosynthetic gene expression in maize.

PMID- 17178170
TI  - Initial serum glucose level as a prognostic factor in the first acute myocardial
      infarction.
AB  - STUDY OBJECTIVE: We assess the prognostic role of initial glucose levels in
      patients with a first acute myocardial infarction in the emergency department
      (ED). METHODS: We conducted a 3-year retrospective cohort study. Patients with a
      first acute myocardial infarction were recruited from the ED of a tertiary
      hospital from January 1, 2001, to December 31, 2003. Initial glucose levels in
      the ED were stratified into 3 levels (normal < 140 mg/dL; intermediate 140 to 200
      mg/dL; and high > or = 200 mg/dL). Logistic and Cox regression models were
      applied to estimate the 1-month short-term and 1-year long-term adverse
      prognoses, respectively. RESULTS: A total of 198 eligible subjects (159 men and
      39 women; mean age 63.1+/-14.2 years) were recruited. The estimated survival
      curves among the 3 initial glucose levels were significantly different (P=.0002).
      After adjustment for sex, age, diabetic status, reperfusion therapy, and infarct
      subtype, the adjusted odds ratio for short-term prognosis progressed with higher
      levels when compared with the normal level (intermediate level: odds ratio 3.87;
      95% confidence interval [CI] 1.71 to 8.78; high level: odds ratio 5.16; 95% CI
      1.97 to 13.51). High initial glucose level was an important risk factor for long
      term adverse prognosis (hazard ratio 3.08; 95% CI 1.59 to 5.98). CONCLUSION: A
      high initial glucose level in the ED is an important and independent predictor of
      short- and long-term adverse prognoses in patients with first acute myocardial
      infarction.

PMID- 17178171
TI  - American College of Surgeons criteria for surgeon presence at initial trauma
      resuscitations: superfluous or necessary?

PMID- 17178172
TI  - A procedural sedation and analgesia fasting consensus advisory: one small step
      for emergency medicine, one giant challenge remaining.

PMID- 17178173
TI  - Hospital emergency surge capacity: an empiric New York statewide study.
AB  - STUDY OBJECTIVE: National policy for emergency preparedness calls for hospitals
      to accommodate surges of 500 new patients per million population in a disaster,
      but published studies have not evaluated the ability of existing resources to
      meet these goals. We describe typical statewide and regional hospital occupancy
      and patterns of variation in occupancy and estimate the ability of hospitals to
      accommodate new inpatients. METHODS: Daily hospital occupancy for each hospital
      was calculated according to admission date and length of stay for each patient
      during the study period. Occupancy was expressed as the count of occupied beds.
      Peak hospital capacity was defined as the 95th percentile highest occupancy at
      each facility. Data obtained from the New York Statewide Planning and Research
      Cooperative System were analyzed for 1996 to 2002. Patients were classified as
      children (0 to 14 years, excluding newborns) or adults. Vacant hospital beds per
      million age-specific population were determined as the difference between peak
      capacity and average occupancy. RESULTS: In New York State, 242 hospitals cared
      for a peak capacity of 2,707 children and 46,613 adults. Occupancy averaged 60%
      of the peak for children and 82% for adults, allowing an average statewide
      capacity for a surge of 268 new pediatric and 555 adult patients for each million
      age-specific population. After the September 11, 2001, attacks, in the New York
      City region, a discretionary modification of admissions and discharges resulted
      in an 11% reduction from the expected occupancy for children and adults.
      CONCLUSION: Typically, there are not enough vacant hospital beds available to
      serve 500 children per million population. Modified standards of hospital care to
      expand capacity may be necessary to serve children in a mass-casualty event.

PMID- 17178174
TI  - Simulation: the new teaching tool.

PMID- 17178175
TI  - Butyrylcholinesterase activity and molecular components in thymus of healthy and
      merosin-deficient Lama2dy mice.
AB  - The laminin-alpha2 chain, referred to as merosin, forms part of the laminin-2
      heterotrimer (alpha2beta1gamma1), which is principally expressed in the basement
      membrane of muscle. Nearly half of patients suffering from congenital muscular
      dystrophy (CMD) have abnormalities in the laminin-alpha2 chain (LAMA2) gene, and
      the merosin-deficient Lama2dy mouse shows CMD. The expression of merosin in
      thymus, the abnormalities in the gland of Lama2dy mice, and the presence of
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in thymus prompted
      us to study the possible effects of the deficiency of merosin on thymus BuChE. We
      found that, while AChE activity decreased by approximately 50% in merosin
      deficient thymus, the deficiency had little effect on BuChE activity. About 65%
      of thymus BuChE activity was extracted with a saline buffer and 30% with 1%
      Triton X-100. Sedimentation analyses and phenyl-agarose chromatography showed
      that thymus contained amphiphilic BuChE monomers (G(1)(A),44%) and dimers
      (G(2)(A),33%), and hydrophilic tetramers (G(4)(H),23%). Binding assays with
      various plant lectins revealed differences between the oligoglycans linked to
      BuChE tetramers and lighter components. The deficiency of merosin had no effect
      on the biosynthesis of thymus BuChE as judged by the lack of major changes
      between control and Lama2dy mice thymuses in the distribution of BuChE molecules
      and the level of lectin binding. The detoxifying action of BuChE, its role as a
      backup to AChE, and the relevance of the cholinergic dialogue between T cells and
      stromal cells for T lymphocyte proliferation, maturation and survival support a
      physiological function for BuChE in thymus.

PMID- 17178176
TI  - Chemotherapy of leishmaniasis Part VI: synthesis and bioevaluation of some novel
      terpenyl S,N- and N,N-acetals.
AB  - Some novel terpene based oxoketene S,N-acetals 2(a-g) and N,N-acetals 3(a-c) have
      been synthesized from oxoketene dithioacetal 1. The compounds were screened for
      their in vivo antileishmanial activity. Some of the compounds showed 50-70%
      inhibition in the hamster model.

PMID- 17178177
TI  - Synthesis and antiparasitic evaluation of bis-2,5-[4-guanidinophenyl]thiophenes.
AB  - A series of bis-2,5-[4-guanidinophenyl]thiophenes were prepared in a five step
      process starting from 2,5-bis[trimethylstannyl]thiophene. The compounds were
      evaluated in vitro against Trypanosoma brucei rhodesiense (T. b. r.), Plasmodium
      falciparum (P. f.), Leshmania donovani (L. d.) and Trypanasoma cruzi (T. c.), and
      in vivo against T. b. r. Certain compounds show promising in vitro activity
      against T. b. r. and P. f. and have superior in vivo activity against T. b. r. to
      that of pentamidine and furamidine.

PMID- 17178180
TI  - A well-tuned engine in New Haven, Connecticut.

PMID- 17178179
TI  - Advantages to the use of rodent hepadnavirus core proteins as vaccine platforms.
AB  - The hepatitis B core antigen (HBcAg) has been proposed as a useful particulate
      carrier platform for poorly immunogenic peptidic and carbohydrate B cell
      epitopes. However, biochemical and immunologic impediments have plagued this
      technology. Specifically, the "assembly" problem characterized by the low yield
      of unstable hybrid particles resulting from the insertion of foreign sequences
      and the "pre-existing immunity" problem due to the fact that the HBcAg is derived
      from a human pathogen have limited the development of this carrier technology. As
      a means of addressing the "pre-existing immunity" problem we have used the core
      proteins from the rodent hepdnaviruses. A number of advantages to the use of the
      rodent hepadnaviral core proteins as opposed to the HBcAg for vaccine design were
      defined including: equal or superior immunogenicity at the T and B cell levels;
      the use of the rodent core proteins does not compromise the anti-HBc diagnostic
      assay; the efficacy of the rodent core proteins as vaccine carriers will not be
      limited by pre-existing anti-HBc antibodies that are present in previously and
      currently HBV-infected persons; and the HBcAg-specific tolerance present in HBV
      chronic carriers can be circumvented by the use of the rodent core proteins.

PMID- 17178178
TI  - Immunogenicity of the P-8 amastigote antigen in the experimental model of canine
      visceral leishmaniasis.
AB  - The P-8 proteoglycolipid complex (P-8 PGLC), an amastigote antigen of Leishmania
      pifanoi, has been demonstrated to induce protection in mouse models, as well as
      to induce Tc1/Th1-like cellular responses in American cutaneous leishmaniasis
      patients. Because the immunization with P-8 PGLC in the murine model does not
      appear to be genetically restricted, we have studied the reactivity of the P-8
      PGLC in Leishmania infantum infected dogs. In this study, it is shown that PBMC
      from experimentally infected dogs (asymptomatic, oligosymptomatic) significantly
      proliferated in response to soluble leishmanial antigen (SLA) or the P-8 PGLC.
      Further, quantification of the gene expression induced by the stimulation with P
      8 in asymptomatically infected dogs showed an up-regulation of IFN-gamma and TNF
      alpha, which were three to 4-fold higher than that induced by soluble Leishmania
      antigen (SLA). While no measurable induction of IL-10 was observed, low levels of
      IL-4 mRNA were observed in response to both P-8 and SLA antigens. Thus, our
      studies establish that P-8 is recognized by infected canines and elicits a
      potentially curative/protective Th1-like immune response. The identification of
      Leishmania antigens that elicit appropriate immune responses across different
      host species (humans, canine) and disease manifestations (cutaneous or visceral)
      could be an advantage in generating a general vaccine for leishmaniasis.

PMID- 17178181
TI  - Gabapentin's acute effect on mood profile -- a controlled study on patients with
      alcohol withdrawal.
AB  - RATIONALE: Delayed beneficial effects of gabapentin on mood were frequently
      reported in various patient populations. This is the first controlled study which
      addressed acute effects of gabapentin on mood. METHODS: Analysis of the German
      version of Profile of Mood States (POMS) throughout a randomised placebo
      controlled, double-blinded study of gabapentin on acute alcohol withdrawal
      [Bonnet, U., Banger, M., Leweke, F.M., Specka, M., Muller, B.W., Hashemi, T.,
      Nyhuis, P.W., Kutscher, S., Burtscheidt, W., Gastpar, M. 2003. Treatment of acute
      alcohol withdrawal with gabapentin -- results from a controlled two-center trial.
      J Clin Psychopharmacol 23, 514-519]. In addition, subjective severity of alcohol
      withdrawal was determined by the Essen Self-Assessment of Alcohol Withdrawal
      Scale (ESA) to control effects of concurrent withdrawal on POMS. Ratings were
      performed at intake (baseline), day 1 (study medication 400 mg q.i.d.), day 2
      (study medication 400 mg q.i.d.) and day 7 (no study medication). RESULTS:
      Analyses could be performed on 46 out of 59 randomised subjects. Within the first
      two days of the study, a significant stronger increase in the POMS-vigour
      subscore occurred in the gabapentin group. A subgroup analysis suggests that
      gabapentin's effect on vigour largely results from a stronger improvement of
      vigour in a small group of 11 patients with co-morbid mild depression (according
      to ICD-10: dysthymia or depressive adjustment disorder). There were no
      significant differences between the treatment groups regarding the other POMS
      subscores (dejection, fatigue, anger) ruling out an overall fast effect on mood.
      Moreover, ESA-measures were not significantly altered indicating a missing effect
      of 400 mg gabapentin q.i.d. on acute alcohol withdrawal itself. After tapering
      off study medication, no more significant differences between gabapentin and
      placebo group were observed on vigour, strongly suggesting that the initial
      effect results from a pharmacological gabapentin action. CONCLUSION: Gabapentin
      selectively accelerated the improvement of the vigour-subscore of patients with
      acute alcohol withdrawal within 48 h. This effect was independent from the
      subjective severity of withdrawal and especially marked in patients with co
      morbid mild depression.

PMID- 17178182
TI  - Benefits and risks of fish consumption Part II. RIBEPEIX, a computer program to
      optimize the balance between the intake of omega-3 fatty acids and chemical
      contaminants.
AB  - In recent years, and based on the importance of fish as a part of a healthy diet,
      there has been a notable promotion of fish and seafood consumption. However, a
      number of recent studies have shown that fish may be a potential source of
      exposure to chemical pollutants, some of them with well known adverse effects on
      human health. Recently, we determined in 14 edible marine species the
      concentrations of eicosapentaenoic acid (EPA) and docosohexaenoic acid (DHA), as
      well as those of a number of chemical contaminants: Cd, Hg, Pb, polychlorinated
      dibenzo-p-dioxins and furans, polychlorinated biphenyls, hexachlorobenzene,
      polycyclic aromatic hydrocarbons, polychlorinated naphthalenes, polybrominated
      diphenylethers and polychlorinated diphenylethers. To quantitative establish the
      intake of these pollutants (risks) versus that of EPA+DHA (benefits), we designed
      a simple computer program, RIBEPEIX. The concentrations of EPA, DHA, and the
      chemical pollutants were introduced into the program. We here present how
      RIBEPEIX may be used as an easy tool to optimize fish consumption: most suitable
      species, frequency of consumption, and size of meals. RIBEPEIX can be useful not
      only for professionals (cardiologists, general physicians, nutritionists,
      toxicologists, etc.), but also for the general population. It is available at: .

PMID- 17178183
TI  - Diphenyl diselenide prevents oxidative damage induced by cigarette smoke exposure
      in lung of rat pups.
AB  - The effect of cigarette smoke exposure on lungs of rat pups was evaluated.
      Animals were exposed to passive cigarette smoke during 3 weeks and a number of
      toxicological parameters in lung of pups were examined, such as lipid
      peroxidation, delta-aminolevulic acid dehydratase (delta-ALA-D) activity,
      components of the enzymatic antioxidant defenses (superoxide dismutase (SOD) and
      catalase activities) and non-enzymatic antioxidant defenses (Vitamin C and non
      protein thiol (NPSH) levels). Furthermore, a possible protective effect of
      diphenyl diselenide, (PhSe)(2), was studied. The results demonstrated an increase
      in lipid peroxidation, an inhibition of delta-ALA-D activity, a reduction of
      Vitamin C and NPSH levels induced by cigarette smoke exposure, indicating damage
      in lungs of rat pups. Oral administration of (PhSe)(2) (0.5mg/kg) restored TBARS
      levels, non-enzymatic antioxidant defenses and activity of delta-ALA-D. These
      results indicated that exposure to cigarette smoke enhanced oxidative stress,
      thereby disturbing the tissue defense system. (PhSe)(2) protected against
      oxidative damage induced by cigarette smoke exposure in lung of rat pups.

PMID- 17178184
TI  - DVD-based or instructor-led CPR education - a comparison.

PMID- 17178185
TI  - A randomized study comparing triptorelin or expectant management following
      conservative laparoscopic surgery for symptomatic stage III-IV endometriosis.
AB  - OBJECTIVE: To investigate the role of adjuvant treatment with gonadotropin
      releasing-hormone agonist (GnRHa) following conservative surgical treatment of
      endometriosis. STUDY DESIGN: Sixty patients in the reproductive age (mean age
      28.6 years), with symptomatic stages III and IV endometriosis following
      laparoscopic surgery and without previous hormonal treatment were enrolled in a
      prospective, randomized, controlled trial to compare the effects of 3-month
      treatment with triptorelin depot-3.75 i.m. (30 patients) versus expectant
      management using placebo injection (30 patients). RESULTS: Six patients (one in
      triptorelin group and five in placebo group) were lost at follow-up, the
      remaining 54 were suitable for analysis. Pelvic pain persistence or recurrence,
      endometrioma relapses and pregnancy rate were evaluated during a 5-year follow
      up. The results of 29 cases treated with triptorelin and 25 that received placebo
      did not show significant differences in pain recurrence (P=1, RR=0.94, 95%
      CI=0.57-1.55), endometrioma relapse (P=0.67, RR=1.29, 95% CI=0.66-2.50), and
      pregnancy rate in infertile women (P=0.80, RR=0.81, 95% CI=0.37-1.80). Curves of
      time of pain recurrence and pregnancy during 5-year follow-up did not show
      significant differences between the two groups (P=0.79 and P=0.51, respectively,
      using Mantel-Haenzsel logrank test). CONCLUSION: Triptorelin treatment after
      operative laparoscopy for stage III/IV endometriosis does not appear to be
      superior to expectant management in terms of prevention of symptoms recurrence
      and endometrioma relapse, and has no influence on pregnancy rate in endometriosis
      associated infertility.

PMID- 17178186
TI  - Nutrition awareness and pregnancy: implications for the life course perspective.
AB  - OBJECTIVE: To explore the influence of a life event (pregnancy) on nutrition
      awareness and the motivations for nutrition behaviour. STUDY DESIGN: In-depth,
      face-to-face interviews with five groups of 12 women: women wishing to conceive a
      child, women in the first, second, and third trimesters of their first pregnancy,
      and women in the first trimester of their second pregnancy. As is common in
      qualitative research, participants were selected on the basis of diversity
      together with maximum representativeness within normal populations with respect
      to socio-demographic characteristics. RESULTS: With respect to nutrition
      awareness, three groups of women can be distinguished: (1) those who are 'going
      all the way'; these women try to live precisely by the book, (2) those who are
      'taking the flexible way'; these women are more aware of their nutrition, but are
      more flexible in handling it, and (3) women who 'continue the same way'; these
      women have a no-nonsense mentality and do not experience essential shifts in
      their nutrition awareness. The extent and fluctuations in nutrition awareness
      throughout preconception and pregnancy are based on three types of motivations,
      the interest of (1) the child, (2) the mother, and (3) the social environment.
      CONCLUSIONS: This study provides indications that preconception and pregnancy
      could indeed be a life event leading to increased general nutrition awareness
      that might influence women's future nutrition-related behaviours.

PMID- 17178187
TI  - Preoperative analgesia with local lidocaine infiltration for abdominal
      hysterectomy pain management.
AB  - OBJECTIVE: To evaluate the impact of preemptive local analgesia at the incision
      site in reducing pain in women undergoing abdominal hysterectomy for a benign
      myomatous uterus. STUDY DESIGN: In this prospective, randomized, double-blinded,
      placebo-controlled study, 20 mL of 1% lidocaine or 0.9% saline was injected at
      the abdominal incision site prior to the performance of the hysterectomy. Thirty
      two women were enrolled in the study, 16 received preemptive analgesia while 14
      were treated by placebo; 2 were excluded. All operations were performed under
      general anesthesia. The standard postoperative pain treatment consisted of oral
      analgesia with ibuprofen (400 mg) in liquid-filled capsules. Morphine (10 mg) was
      used for rescue analgesia. Pain intensity was self-evaluated with the use of a
      100 mm visual analog scale. RESULTS: Compared to the placebo group, women who
      received preemptive analgesia with lidocaine 1% perceived a significant reduction
      in postoperative pain in the first hours after surgery (2 h: 50.1+/-27.9 versus
      70.6+/-22.6, p=0.043; 5 h: 42.5+/-25.2 versus 64.6+/-28.3, p=0.043; 8 h: 31.2+/
      22.4 versus 53.3+/-30.3, p=0.031). CONCLUSION: Preemptive analgesia with
      lidocaine 1% is a simple, cheap and efficient mode to reduce pain in the first
      hours after hysterectomy.

PMID- 17178188
TI  - Additional surgical intervention after radical prostatectomy, radiation therapy,
      androgen-deprivation therapy, or watchful waiting.
AB  - OBJECTIVES: The amount of additional surgical procedures that cancer patients
      undergo following their initial treatment is one means of measuring the impact
      that cancer and cancer treatment has on their quality of life. In this study we
      looked for treatment-related differences in the need for additional surgical
      intervention among men with nonmetastatic prostate cancer within 66 mo of their
      initial treatment. METHODS: Data for this study were from the National Cancer
      Institutes Surveillance, Epidemiology, and End Results (SEER) program and from
      the Medicare claims database. We searched the claims database for procedure codes
      indicating artificial urinary sphincter procedures, cystoscopy, urethral
      dilation, transurethral resection of the prostate (TURP) and bladder-neck
      incision, bladder irrigation/cystotomy, or nephrostomy. RESULTS: Of the 12,711
      patients in our study, 3940 (31.0%) were initially treated by radical
      prostatectomy (RP), 3950 (31.1%) by radiation therapy (RT), 1209 (9.5%) by
      androgen-deprivation therapy (ADT), and 3612 (28.4%) by watchful waiting (WW).
      The percentage of patients who underwent cystoscopy 6-66 mo after their initial
      treatment ranged narrowly from 22% to 24% among members of the four treatment
      groups. In the RP group, 5.2% had artificial urinary sphincter procedures; 6.8%
      of the RT group, 8.2% of the ADT group, and 10.1% of the WW group had
      TURP/bladder-neck procedures compared with 3.7% of the RP group; and 12.5-16.2%
      of members in the four groups had urethral dilation procedures. CONCLUSIONS: Over
      one third of prostate cancer patients needed surgical intervention within 66 mo
      of their initial treatment despite the type of initial treatment.

PMID- 17178189
TI  - Sequential separation of lanthanides, thorium and uranium using novel solid phase
      extraction method from high acidic nuclear wastes.
AB  - A novel grafted polymer for selective extraction and sequential separation of
      lanthanides, thorium and uranium from high acidic wastes has been developed by
      grafting Merrifield chloromethylated (MCM) resin with octyl(phenyl)-N,N
      diisobutylcarbamoyl-methylphosphine oxide (CMPO) (MCM-CMPO). The grafting process
      is well characterized using FT-IR spectroscopy, (31)P and (13)C CPMAS (cross
      polarized magic angle spin) NMR spectroscopy and CHNPS elemental analysis. The
      influence of various physico-chemical parameters during metal ion extraction by
      the resin phase are studied and optimized by both static and dynamic methods. The
      resin shows very high sorption capacity values of 0.960mmolg(-1) for U(VI),
      0.984mmolg(-1) for Th(IV), 0.488mmolg(-1) for La(III) and 0.502mmolg(-1) for
      Nd(III) under optimum HNO(3) medium, respectively. The grafted polymer shows
      faster rate exchange kinetics (<5min is sufficient for 50% extraction) and
      greater preconcentration ability, with reusability exceeding 20 cycles. During
      desorption process, sequential separation of the analytes is possible with
      varying eluting agents. The developed grafted resin has been successfully applied
      in extracting Th(IV) from high matrix monazite sand, U(VI) and Th(IV) from
      simulated nuclear spent fuel mixtures. All the analytical data is based on
      triplicate analysis and measurements are within 3.5% rsd reflecting the
      reproducibility and reliability of the developed method.

PMID- 17178190
TI  - Removal of congo red using activated carbon and its regeneration.
AB  - Activated carbon is used for the removal of colored toxic congo red dye. The
      effects of different operating conditions like, initial dye concentration,
      contact time, pH and temperature are studied for adsorption of congo red by a
      known amount of activated carbon (1.0g/L) under stirred batch condition. The zero
      point of charge of the activated carbon is found about 6.6. About 90% dye is
      removed for initial concentration of 50 and 100mg/L, it is about 80% at pH 7.0.
      Maximum adsorption (about 100%) of dye is observed at pH 2.0 for the
      concentration range studied here. Freundlich isotherm is found to fit the
      equilibrium data more adequately. Pseudo second order kinetic model explain
      successfully the kinetic data. The surfactant enhanced carbon regeneration (SECR)
      technique using both cationic and anionic surfactants is adopted for the
      regeneration of spent carbon by desorbing the dye. A kinetic model for dye
      desorption from the commercial activated carbon (CAC) is also proposed. Anionic
      surfactants show better performance than the cationic ones. Efficiency of dye
      desorption using surfactants is also compared with the desorption using pH
      change.

PMID- 17178191
TI  - Music increases frontal EEG coherence during verbal learning.
AB  - Anecdotal and some empirical evidence suggests that music can enhance learning
      and memory. However, the mechanisms by which music modulates the neural activity
      associated with learning and memory remain largely unexplored. We evaluated
      coherent frontal oscillations in the electroencephalogram (EEG) while subjects
      were engaged in a modified version of Rey's Auditory Verbal Learning Test (AVLT).
      Subjects heard either a spoken version of the AVLT or the conventional AVLT word
      list sung. Learning-related changes in coherence (LRCC) were measured by
      comparing the EEG during word encoding on correctly recalled trials to the
      immediately preceding trial on which the same word was not recalled. There were
      no significant changes in coherence associated with conventional verbal learning.
      However, musical verbal learning was associated with increased coherence within
      and between left and right frontal areas in theta, alpha, and gamma frequency
      bands. It is unlikely that the different patterns of LRCC reflect general
      performance differences; the groups exhibited similar learning performance. The
      results suggest that verbal learning with a musical template strengthens coherent
      oscillations in frontal cortical networks involved in verbal encoding.

PMID- 17178192
TI  - A hypoxia-inducible gene expression system using erythropoietin 3' untranslated
      region for the gene therapy of rat spinal cord injury.
AB  - Many neurologic disorders are accompanied by ischemic injury during the
      pathologic process. To develop a controllable and injury-specific gene therapy
      system for the neurologic disorders, we constructed a hypoxia inducible plasmid
      with the erythropoietin (Epo) 3' untranslated region (UTR), which can enhance the
      stability of target mRNAs in response to hypoxia. The Epo 3' UTR was inserted at
      the 3' flanking region of luciferase gene in pSV-Luc, resulting in the
      construction of pSV-Luc-EpoUTR. In pEpo-SV-Luc-EpoUTR, the Epo enhancer was
      inserted into the upstream of the SV40 promoter to increase the hypoxia
      inducibility. The plasmids were evaluated in N2a mouse neuroblastoma cells under
      hypoxic conditions and in a rat spinal cord injury (SCI) model. The results
      showed that the Epo 3' UTR alone showed a three-fold increase in luciferase
      activity in hypoxic N2a cells as well as in the rat SCI model when compared to
      the sham control. In contrast, the Epo 3' UTR showed no effect on the luciferase
      activity in the presence of the Epo enhancer, probably because the Epo enhancer
      was more sensitive to hypoxia and showed a dominant effect. However, the Epo
      enhancer itself showed high level of luciferase activity even in normoxia (about
      five to eight-folds increase), while the Epo 3' UTR did not show enhanced
      background activity. Immunohistochemical staining showed expression of luciferase
      from pSV-Luc-EpoUTR both in neurons and astrocytes around the injured spinal cord
      of rat. These results suggest that the Epo 3' UTR could provide a specific and
      safe system for the hypoxia-inducible gene therapy of the neurologic disorders
      including SCI.

PMID- 17178193
TI  - Characterization of cannabinoid-binding sites in zebrafish brain.
AB  - We present here the pharmacological characterization of cannabinoid-binding sites
      in zebrafish brain homogenates using radiolabeled binding techniques. The
      nonselective agonist [3H]-CP55940 binds with high affinity (KD = 0.50+/-0.06 nM
      and a Bmax = 1047+/-36.01 fmol/mg protein), displaying one binding site. The
      slightly CB2 selective agonist [3H]-WIN55212-2 also binds with high affinity to
      zebrafish brain membranes displaying two different binding sites with affinities
      KD1 = 0.35+/-0.09 nM and KD2 = 105.81+/-66.36 nM. Competition binding assays
      using [3H]-WIN55212-2 and several unlabeled ligands were performed. WIN55212-2
      significantly displaced the tritiated ligand binding showing the two binding
      sites observed with its tritiated homologous, while the slightly selective CB1
      cannabinoid ligand HU-210, the nonselective cannabinoid ligand CP55940 and the
      endogenous cannabinoid ligand anandamide presented one binding site. Also, the
      functionality of these cannabinoid sites was analyzed using the known
      [35S]GTPgammaS assay. All the agonist used presented an agonist profile and the
      rank order for potency was HU-210 > WIN55212-2 > CP55940 >anandamide. Our results
      provide evidence that, although some of the typical cannabinoid ligands for
      mammalian receptors do not fully recognize the cannabinoid-binding sites in
      zebrafish brain, the activity of the endogenous zebrafish cannabinoid system
      might not significantly differ from that displayed by the cannabinoid system
      described in other species. Hence the study of zebrafish cannabinoid activity may
      contribute to an understanding of the endogenous cannabinoid system in higher
      vertebrates.

PMID- 17178194
TI  - Analysis of plasma proteins that bind to glycosaminoglycans.
AB  - Glycosaminoglycan-binding proteins, with specific emphasis on dermatan sulfate,
      have been investigated in human plasma by affinity chromatography, mass
      spectrometry and Western blotting. Diluted plasma was applied to affinity columns
      and bound protein was eluted with 500 mM NaCl. Dermatan sulfate and heparan
      sulfate bound 7% of the total protein. Heparin bound 22% of the total protein,
      but chondroitin sulfate A bound only 0.23%. Mass spectrometric analysis
      identified 20 proteins as dermatan-sulfate-binding proteins, most of which were
      confirmed by Western blotting. Some of these binding proteins, such as
      fibrinogen, fibronectin, apolipoprotein B, LMW kininogen, inter-alpha-trypsin
      inhibitor, and factor H, were degraded to various extents during the
      chromatography step, but this degradation could be prevented by the inclusion of
      a serine protease inhibitor. The protein fraction binding to the dermatan sulfate
      column showed amidase activity, whereas that binding to the heparan sulfate and
      heparin columns showed 1/2 and 1/20, respectively, of the activity of the
      dermatan sulfate binding fraction. Dermatan sulfate was similar to heparan
      sulfate with respect to its capacity to bind plasma proteins and its activation
      of protease, but differed from chondroitin sulfate and heparin in these
      properties.

PMID- 17178195
TI  - Tamoxifen: important considerations of a multi-functional compound with organ
      specific properties.
AB  - Tamoxifen remains a frontline treatment for hormone-responsive breast cancer
      despite its use being associated with a 2-7-fold elevated risk of developing
      endometrial carcinoma. Several groups have investigated whether tamoxifen induces
      DNA-damaging (genotoxic) versus non-genotoxic mechanisms. Some studies point to
      the presence of tamoxifen-DNA adducts while others suggest otherwise. In many of
      these studies, the histological sub-type has not been considered; as type 1
      carcinomas are associated with PTEN and KRAS2 mutations whereas type 2 carcinomas
      exhibit TP53 and ERBB-2 mutations, the absence of this information makes
      comparisons between such independent investigations difficult. An examination of
      the sub-types of endometrial carcinoma points to histological and mechanistic
      distinctions between sporadic and tamoxifen-associated disease; this could
      suggest differing aetiologies. On this basis, we propose a dual mechanism of
      action highlighted by the different patterns of endometrial carcinoma sub-types.
      Tamoxifen may initially be pro-oestrogenic in the endometrium giving rise to
      elevated type 1 endometrioid carcinoma occurrence whereas after long-term use,
      there is an increase of type 2 disease or malignant mixed mullerian tumours
      associated with a hormone-independent mechanism of action. Despite these
      associated risk factors, and the introduction of new selective oestrogen receptor
      modulators (SERMs), we suggest that the organ-specific pleiotrophic effects of
      tamoxifen mean that this effective therapeutic agent for breast cancer will
      continue to have significant usage. The focus of future research should
      concentrate on the different aetiologies of tamoxifen-associated endometrial
      carcinomas while efforts continue to develop future SERMs.

PMID- 17178197
TI  - Motives for cannabis use as a moderator variable of distress among young adults.
AB  - This study examined the moderating effect of social and coping motives on
      distress among young cannabis-using adults. A random sample of 2031 young Swiss
      adults was interviewed by means of a computer-assisted telephone interview.
      Cannabis users showed more distress, less positive health behaviour and higher
      hedonism compared to non-users. Taking motive for use as a moderator variable
      into consideration, it became evident that only cannabis users with coping
      motives showed lower mental health, more symptoms of psychopathology, more
      psychosocial distress and more life events than non-users. Young adults with
      social motives for use on the other hand did not differ from non-users in terms
      of distress. These differences between cannabis users with social and those with
      coping motives remained stable over two years. In both subgroups, participants
      with regular cannabis use at baseline did not increase distress nor did
      participants with higher distress at baseline increase the frequency of their
      cannabis use. Our results suggest that secondary prevention for cannabis users
      should target especially young adults with coping motives for use.

PMID- 17178196
TI  - Anti-inflammatory property of the cannabinoid agonist WIN-55212-2 in a rodent
      model of chronic brain inflammation.
AB  - Cannabinoid receptors (CBr) stimulation induces numerous central and peripheral
      effects. A growing interest in the beneficial properties of manipulating the
      endocannabinoid system has led to the possible involvement of CBr in the control
      of brain inflammation. In the present study we examined the effect of the CBr
      agonist, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo[1,2,3-de]
      1,4benzoxazin-6-yl]-1-naphthalenyl-methanone mesylate (WIN-55212-2), on
      microglial activation and spatial memory performance, using a well-characterized
      animal model of chronic brain inflammation produced by the infusion of
      lipopolysaccharide (LPS, 250 ng/h for 3 weeks) into the fourth ventricle of young
      rats. WIN-55212-2 (0.5 or 1.0 mg/kg/day, i.p.) was administered for 3 weeks.
      During the third week of treatment, spatial memory ability was examined using the
      Morris water-maze task. We found that 0.5 and 1 mg/kg WIN-55212-2 reduced the
      number of LPS-activated microglia, while 1 mg/kg WIN-55212-2 potentiated the LPS
      induced impairment of performance in the water maze task. Cannabinoid receptors 1
      were not expressed by microglia and astrocytes, suggesting an indirect effect of
      WIN-55212-2 on microglia activation and memory impairment. Our results emphasize
      the potential use of CBr agonists in the regulation of inflammatory processes
      within the brain; this knowledge may lead to the use of CBr agonists in the
      treatment of neurodegenerative diseases associated with chronic
      neuroinflammation, such as Alzheimer disease.

PMID- 17178198
TI  - Associations between dieting and smoking-related behaviors in young women.
AB  - Many young women report smoking due to weight concerns, but little is known about
      the relationship between weight concerns and current smoking behavior. The
      present study examined smoking topography and the acute sensory and physiological
      responses to smoking in dieting and non-dieting young women. In addition, the
      effect of presentation of food cues on these responses was examined. Self
      reported female current dieters (n=15) and non-dieters (n=15) attended two
      laboratory sessions (food cues present/food cues absent). Physiological and
      subjective responses were recorded pre- and post-cigarette at each session.
      Smoking topography was assessed by video analysis. Dieters scored higher than non
      dieters on measures of weight control smoking, dietary restraint, and
      disinhibition. At both sessions, they smoked less of the cigarette, had shorter
      inhalation durations, longer inter-puff intervals, experienced smaller
      physiological effects and gave lower ratings of the sensory aspects of smoking
      than non-dieters. The presence of food cues did not alter smoking topography or
      sensory/physiological responses but the dieters reported a greater desire to
      smoke in the presence of food cues. These data suggest that sensory factors may
      be less important influences on smoking for weight control smokers than non
      weight control smokers and that further investigation of the role of food cues in
      maintaining smoking behavior in weight control smokers is warranted.

PMID- 17178200
TI  - Dry powder inhalation of colistin sulphomethate in healthy volunteers: A pilot
      study.
AB  - BACKGROUND: Pulmonary administration of the antimicrobial drugs colistin
      sulphomethate and tobramycin has been shown to be effective in slowing down
      pulmonary deterioration in cystic fibrosis (CF) patients. Both drugs are
      administered by liquid nebulisation, a technique known to have disadvantages. Dry
      powder inhalation may be an attractive alternative. We investigated inhalation of
      colistin sulphomethate dry powder using a newly developed Twincer device in
      healthy volunteers. METHODS: Eight healthy volunteers inhaled a single dose of
      25mg colistin sulphomethate dry powder each, using the Twincer inhaler. The
      median diameter (X(50)) of the dry powder was 1.6 microm (X(10)=0.7 microm,
      X(90)=3.1 microm), measured by laser diffraction technique. Pulmonary function
      tests were performed before, 5 and 30 min after inhalation. Serum samples were
      drawn at t=15 min, 45 min, 1.5h, 2.5h, 3.5h, 5.5h, 7.5h and 24h after inhalation.
      RESULTS: The colistin sulphomethate dry powder inhaler was well tolerated: no
      clinically relevant effect on FEV(1) was observed nor did the volunteers
      experience adverse effects. CONCLUSION: Dry powder inhalation of colistin
      sulphomethate using the Twincer inhaler is well tolerated by healthy volunteers.
      A pilot study in cystic fibrosis patients is therefore considered safe in
      developing a dry powder inhalation of colistin for everyday CF treatment.

PMID- 17178199
TI  - Effects of methylenedianiline on tight junction permeability of biliary
      epithelial cells in vivo and in vitro.
AB  - Methylenedianiline (DAPM) is considered a cholangiodestructive toxicant in vivo.
      Increases in biliary inorganic phosphate (P(i)) and glucose occur prior to
      biliary epithelial cell (BEC) injury, which could be due to increased
      paracellular permeability and/or impairment of P(i) and glucose uptake by BEC. To
      evaluate these possibilities, we induced mild injury [loss of BEC from major bile
      ducts (6 h), ultrastructural alterations in BEC mitochondria and Golgi cisternae
      (3 h), and striking increases in biliary P(i) and glucose (3-6 h)] with 25 mg
      DAPM/kg and then assessed temporal alterations in tight junction (TJ)
      permeability by measuring bile to plasma (B:P) ratios of [(3)H]-inulin.
      Parameters maintained by hepatocytes in bile were unchanged (bile flow, bile
      salts, bilirubin) or only transiently perturbed (protein, glutathione). Minimal
      elevations in B:P ratios of inulin occurred temporally later (4 h) in DAPM
      treated rats than increases in biliary P(i) and glucose. To confirm a direct
      effect of DAPM on BEC TJs, we measured transepithelial resistance (TER) and bi
      ionic potentials of BEC monolayers prior to and after exposure to pooled (4-6)
      bile samples collected from untreated rats (Basal Bile) or rats treated with 50
      mg DAPM/kg (DAPM-Bile). BEC TJs were found to be cation selective. Exposure to
      DAPM-Bile for 1 h decreased TERs by approximately 35% and decreased charge
      selectivity of BEC TJs while exposure to Basal Bile had no effects. These
      observations indicate that DAPM-Bile impairs paracellular permeability of BEC in
      vitro. Further, our in vivo model suggests that increases in paracellular
      permeability induced by DAPM are localized to BEC because bile flow and
      constituents excreted by hepatocytes were unchanged, BEC damage was temporally
      correlated with increases in biliary P(i) and glucose, and elevations in B:P
      ratios of inulin were delayed and minimal.

PMID- 17178202
TI  - Antimicrobial activity of some medicinal barks used in Peruvian Amazon.
AB  - The aim of this study was to evaluate the antimicrobial activity of six barks
      traditionally used in Calleria District (Ucayali Department, Peru) for treating
      conditions likely to be associated with microorganisms. Ethanol extracts of stem
      barks of Abuta grandifolia (Menispermaceae), Dipteryx micrantha (Leguminosae),
      Cordia alliodora (Boraginaceae), Naucleopsis glabra (Moraceae), Pterocarpus
      rohrii (Leguminosae), and root bark of Maytenus macrocarpa (Celastraceae) were
      tested against nine bacteria and one yeast using the broth microdilution method.
      All plants possessed significant antimicrobial effect, however, the extract of
      Naucleopsis glabra exhibited the strongest activity against Gram-positive
      bacteria (MICs ranging from 62.5 to 125 microg/ml), while the broadest spectrum
      of action was shown by the extract of Maytenus macrocarpa, which inhibited all
      the strains tested with MICs ranging from 125 to 250 microg/ml.

PMID- 17178201
TI  - Effect of physical properties of troglitazone crystal on the molecular
      interaction with PVP during heating.
AB  - This study examined the effect of physical properties of troglitazone drug
      substance on the molecular interaction with polyvinylpyrrolidone K30 (PVP) during
      preparation by a closed melting method. Milling was conducted using impact and
      jet mills to change the physical properties of troglitazone, such as particle
      size, specific surface area, surface free energy and acidic-basic parameters.
      Solid dispersions (SDs) prepared from milled troglitazone, irrespective of
      milling method, showed almost 100% dissolution when not less than 7.5% of water
      was added during heating. SDs prepared from unmilled troglitazone showed almost
      100% dissolution when not less than 12.8% of water was added during heating.
      Physical mixture (PM) containing unmilled troglitazone must be heated above at
      least 50 degrees C higher than the glass transition temperature (T(g)) of PVP to
      obtain an SD showing 100% dissolution, while PMs containing milled troglitazone
      could be heated above only 20 degrees C higher than the T(g) of PVP to obtain an
      SD showing 100% dissolution. The melting points of troglitazone in PMs containing
      milled troglitazone, irrespective of milling method, were lower than those in PMs
      containing unmilled troglitazone. These results indicated that specific
      interaction could occur more easily during heating between milled troglitazone
      and PVP during preparation by a closed melting method. In addition, Fourier
      transform infrared study indicated that hydrogen bonding could occur between the
      N-H of troglitazone and the C=O of PVP.

PMID- 17178203
TI  - Development of a harmonised method for the profiling of amphetamines V:
      Determination of the variability of the optimised method.
AB  - This paper is the fifth in a series of six in relation to the development of a
      harmonised method for the profiling of amphetamine [L. Aalberg, K. Andersson, C.
      Bertler, H. Boren, M.D. Cole, J. Dahlen, Y. Finnon, H. Huizer, K. Jalava, E. Kaa,
      E. Lock, A. Lopes, A. Poortman-van der Meer, E. Sippola, Development of a
      harmonised method for the profiling of amphetamines I. Synthesis of standards and
      compilation of analytical data, Forensic Sci. Int. 149 (2005) 219-229; L.
      Aalberg, K. Andersson, C. Bertler, M.D. Cole, Y. Finnon, H. Huizer, K. Jalava, E.
      Kaa, E. Lock, A. Lopes, A. Poortman-van der Meer, E. Sippola, J. Dahlen,
      Development of a harmonised method for the profiling of amphetamines II.
      Stability of impurities in organic solvents, Forensic Sci. Int. 149 (2005) 231
      241]. The third paper [K. Andersson, K. Jalava, E. Lock, L. Aalberg, Y. Finnon,
      H. Huizer, E. Kaa, A. Lopes, A. Poortman-van der Meer, M.D. Cole, J. Dahlen, E.
      Sippola, Development of a harmonised method for the profiling of amphetamines
      III. Development of the gas chromatographic method, Forensic Sci. Int., in press]
      dealt with the optimisation of the gas chromatographic and detection methods
      whereas the fourth paper [K. Andersson, K. Jalava, E. Lock, Y. Finnon, S.
      Stevenson, L. Aalberg, H. Huizer, E. Kaa, A. Lopes, A. Poortman-van der Meer,
      M.D. Cole, J. Dahlen, E. Sippola, Development of a harmonised method for the
      profiling of amphetamines IV. Optimisation of sample preparation, Forensic Sci.
      Int., in press] concerned the optimisation of the extraction method prior to GC
      analysis. This paper is a study of the optimised method in order to determine its
      stability. Investigations of within and between day variations were carried out
      in four laboratories. Moreover, variations between laboratories were also
      determined. Both flame ionisation detector (FID) and MS detection were used. One
      laboratory studied nitrogen-phosphorous detector (NPD) detection as well. For
      this task, 12 batches of amphetamine were prepared. Six of them were synthesised
      via the Leuckart route, three via the nitrostyrene route and three via the
      reductive amination route [A.M.A. Verweij, Impurities in illicit drug
      preparations: amphetamine and methamphetamine, Forensic Sci. Rev. 1 (1989) 2-11].
      Taking into account all studied target compounds and the average results from
      four laboratories, the within day variation was around 6% for FID and 5% for MS,
      the between days variation was around 10% for FID and 8% for MS. For NPD
      detection, within day variation was 5% and between days variation 9% (only one
      laboratory). Finally, the inter-laboratory variation was about 12% for FID (four
      laboratories) and 10% for MS (three laboratories).

PMID- 17178204
TI  - Elemental analysis of 3,4-methylenedioxymethamphetamine (MDMA): A tool to
      determine the synthesis method and trace links.
AB  - The elemental composition of 3,4-methylenedioxymethamphetamine (MDMA) powders and
      tablets was determined. The objective was the identification of the synthesis
      method and application of the elemental profile in comparative analysis. The
      developed analytical method comprised the digestion of a sample followed by
      quantitative analysis with inductive coupled plasma mass spectrometry (ICP-MS)
      and inductive coupled plasma atomic emission spectroscopy (ICP-AES). The sample
      collection consisted of a unique set of MDMA powders (57) from illicit production
      sites and MDMA tablets (97) taken from large seizures (over 500 tablets) in the
      Netherlands. The production method of MDMA could be determined for 89 of the 97
      tablets. In 84 cases reductive amination using Pt as the catalyst was used, in
      four cases reductive amination using NaBH(4) or a similar reducing agent was
      employed and one mixed sample (Pt and B) was found. None of the MDMA tablets were
      assigned to the aluminium amalgam method. Using the elemental profile, 13 links
      were identified within the 97 MDMA tablets using cluster analysis based on
      Pearson correlations. Of these links 10 were corroborated by additional analyses.

PMID- 17178205
TI  - The first reported case of Menkes disease caused by an Alu insertion mutation.
AB  - We present the first reported case of Menkes disease caused by an Alu element
      insertion mutation that interfered with splicing regulatory elements. A whole
      young AluYa5a2 element, which was 382-bp long, was identified within exon 9 of
      the ATP7A gene, and all of exon 9 was aberrantly skipped in the cDNA, resulting
      in severely truncated proteins. To confirm whether the aberrant skipping resulted
      in Alu insertion, an exonic splicing enhancer finder was used. The Alu element
      created two new high-score exonic splicing enhancer sequences in the mutation
      located near the site of the insertion. Exon 9, which encodes the first and
      second transmembrane domains, is necessary for the normal function of the ATP7A
      protein.

PMID- 17178206
TI  - Transcranial color Doppler sonography on healthy pre-school children: flow
      velocities and total cerebral blood flow volume.
AB  - Transcranial color Doppler sonography (TCCD) is a useful tool for intracranial
      investigation. Using TCCD to calculate total cerebral blood flow volume (TCBFV)
      can be a useful indicator for intracranial hemodynamic status. We performed a
      series study of TCCD on 60 healthy kindergarten students. Peak-systolic, end
      diastolic, and mean blood velocities of major cerebral arteries, and depth of
      flow waves were measured. We also collected Gosling pulsatile index (PI) and
      Pourcelot resistance index (RI) of the arteries. TCBFV was calculated from the
      mean blood flood velocity and vessel chamber size of the internal carotid artery
      (ICA) and basilar artery (BA). Fifty children completed the examinations. The
      TCBFV was 1538+/-416 ml/min with mean cerebral blood flow volume of 571+/-241
      ml/min for the ICA system and 983+/-343 ml/min for the BA system. PI, RI, and the
      velocities of A1, A2, M1, M2, BA, ICA, and TCBFV were not significantly different
      between girls and boys in this age group. In this study, we used TCCD to
      determine the normal data of main cerebral arteries and TCBFV of pre-school
      children in Taiwan. The reference data of velocities and other parameters of main
      cerebral arteries from our study may serve as a guide for additional pediatric
      cerebral hemodynamic studies.

PMID- 17178207
TI  - Sentinel node biopsy in non-palpable breast cancer and in patients with a
      previous diagnostic excision.
AB  - AIM: As a means of staging the axilla with minimal surgical trauma, sentinel
      lymph node biopsy (SNB) has dramatically altered the management of early-stage
      breast cancer. The aim of this prospective multicentre study was to assess the
      safety of the method in cases of non-palpable tumours and in cases with an open
      biopsy prior to SNB. METHOD: In the period 1999-2001, 57 non-palpable breast
      cancers and 75 patients with diagnostic biopsy were collected prospectively to
      the first part of the study. In the second part, 745 patients with non-palpable
      breast cancers and 86 cases with prior open surgery diagnosed between 2000 and
      2005 were followed up till the end of 2005. All patients in the first part of the
      study had an axillary clearance irrespective of sentinel node status, whereas in
      the second part axillary clearance was done only if the sentinel node was
      metastatic. RESULTS: The detection rate was 95% in the group of non-palpable
      breast cancers, with a false negative rate of 5.6% (1/18), and the corresponding
      figures for the group with prior intervention were 96% and 10% (2/20). Two
      axillary recurrences, after a negative SNB at primary surgery, were found in the
      non-palpable group after 16 and 17 months, respectively. No axillary recurrence
      has been observed in the group of cancers with a prior open biopsy. Four women in
      the non-palpable group and two women with a diagnostic operation experienced
      distant metastases. CONCLUSION: We conclude that SNB is a safe procedure for
      women with non-palpable breast cancer, as well as after previous open diagnostic
      excision.

PMID- 17178208
TI  - Implication of the transcription factor E2F-1 in the modulation of neuronal
      apoptosis.
AB  - Neurodegenerative diseases as Alzheimer's disease, Parkinson's disease and other
      neurological disorders remain major problem worldwide since is currently no
      effective treatment. Thus, studying the mechanisms involved in neuronal apoptotic
      pathways is imperative if drugs that might stop or delay these disease processes
      are to be synthesized. In recent years it has become evident that mitochondria
      are key component of the neuronal apoptotic route. In addition to mitochondria,
      other intracellular components have been implicated in this process. Thus, DNA
      damage and re-entry into the cell cycle may constitute a common pathway in
      apoptosis in neurological diseases. The implication of cell cycle in
      neurodegenerative disorders is supported by data on the brain of patients who
      showed an increase in cell cycle protein expression. Indeed, studies performed in
      neuronal cell preparations indicate that re-entry into the cell cycle and, more
      specifically, an increase in the expression of E2F-1 transcription role of DNA
      damage/repair as a potential mechanism in cell cycle re-entry. In this context,
      ataxia telangiectasia mutated protein could be the enzyme responsible for
      neuronal apoptosis activation. Furthermore, the potential routes involved in E2F
      1 induced apoptosis, p53-dependent and p53-independent, are similarly reviewed.
      Under this hypothesis, multiple pathways have been suggested, including the route
      of caspases. Finally, given the increasing experimental data on the
      neuroprotective and antiapoptotic effects of cyclin dependent kinase CDK
      inhibitory drugs, including flavopiridol, their application for the treatment of
      neurological disorders is proposed.

PMID- 17178209
TI  - The association between fatigue and inflammatory marker levels in cancer
      patients: a quantitative review.
AB  - Increased cytokine and neopterin levels may be responsible for cancer-related
      fatigue, the most common complaint among cancer patients. We quantitatively
      reviewed empirical findings on this topic, focusing on studies not using
      immunotherapy. PubMed, PsychINFO and BIOSIS were searched for articles published
      until July 2006. Studies remained unweighted or were weighted according to study
      quality and sample size. The correlation coefficient r was used for statistical
      analyses. Heterogeneity among the studies was examined using the I(2) index.
      Eighteen studies (1037 participants) of moderately high methodological quality
      were located and statistically analyzed. Most studies measured more than one
      inflammatory marker, resulting in a total of 58 correlation estimates. In 31 of
      these, we had to input a null correlation because results had been simply
      reported as nonsignificant and no further statistical information was available.
      General analyses based on weighting according to sample size showed a
      significantly positive correlation between fatigue and circulating levels of
      inflammatory markers (r=0.11, p<0.0001). Analyses of individual inflammatory
      markers revealed significantly positive correlations between fatigue and IL-6
      (r=0.12, p=0.004), fatigue and IL-1 ra (r=0.24, p=0.0005), and fatigue and
      neopterin (r=0.22, p=0.0001). Fatigue did not correlate significantly with IL-1
      beta (r=0.05, p=0.42) or TNF-alpha (r=0.04, p=0.34). Given its preliminary nature
      due to the limited available data, this quantitative review showed a positive
      association between cancer-related fatigue and circulating levels of IL-6, IL-1
      ra and neopterin. Future studies examining the relationship between cancer
      related fatigue and inflammation would benefit from multiple rather than single
      blood sampling and from repeated daily ratings of the multidimensional nature of
      fatigue.

PMID- 17178210
TI  - Repeated social defeat causes increased anxiety-like behavior and alters
      splenocyte function in C57BL/6 and CD-1 mice.
AB  - The experimental model, social disruption (SDR), is a model of social stress in
      which mice are repeatedly attacked and defeated in their home cage by an
      aggressive conspecific. In terms of the impact of this stressor on the immune
      response, SDR has been reported to cause hyperinflammation and glucocorticoid
      insensitivity. To this point however, the behavioral consequences of SDR have not
      been thoroughly characterized. Because social defeat has been reported to cause
      anxiety- and depressive-like behaviors, the current study was designed to assess
      whether SDR also causes anxiety- and depressive-like behaviors. Using the
      light/dark preference test and the open field test as tools to measure behaviors
      characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice
      subjected to SDR displayed increased anxiety-like behavior. The increase in
      anxiety-like behaviors persisted for at least 1 week after the cessation of the
      stressor. In contrast, depressive-like behaviors were not elicited by SDR as
      assessed by the forced swim test or the tail suspension test. These data indicate
      that social disruption stress causes an increase in anxiety-like behaviors, but
      not depressive-like behaviors.

PMID- 17178211
TI  - The protective effects of melatonin and Vitamin E on antioxidant enzyme
      activities and epididymal sperm characteristics of homocysteine treated male
      rats.
AB  - The aims of this study were to investigate the effects of homocysteine (Hcy) on
      epididymal sperm characteristics, plasma testosterone level and biochemical
      changes related to oxidative stress and to examine the effects of melatonin (Mlt)
      or Vitamin E (VE) administration on these parameters in Hcy-treated male rats. In
      this study, 32 adult male albino rats of Wistar strain were used. The rats were
      randomly divided into four groups. The first group of rats received only Hcy
      (0.71 mg/kg/day) intraperitonially (ip) for 6 weeks. The second group of rats was
      given Hcy along with simultaneous administration of Mlt (1mg/kg/day)
      subcutaneously. The third group of rats received Hcy along with simultaneous
      administration of VE (125 mg/kg/day, ip). The fourth group of rats served as
      control during 6 weeks and was daily given 0.1 mL of physiological saline (NaCl,
      0.9%) ip. While the plasma malondialdehyde level significantly (p<0.05)
      increased, the plasma superoxide dismutase, glutathione peroxidase and catalase
      activities significantly (p<0.05) decreased in Hcy-treated rats when compared to
      control rats. Furthermore, the epididymal sperm concentration, the percentage of
      progressive sperm motility and plasma testosterone level were significantly
      (p<0.05) lower in Hcy-treated rats than those of the control rats. The
      simultaneous administration of Mlt or VE to Hcy-treated animals impeded the
      decrease in the plasma antioxidant enzyme activities, testosterone level, the
      epididymal sperm concentration and motility. In conclusion, this study indicates
      that chronic administration of Hcy has the harmful effect on the epididymal sperm
      characteristics of male rats. The administration of Mlt or VE can prevent adverse
      effects of Hcy on the plasma antioxidant enzyme activities, testosterone level,
      epididymal sperm count and motility in male rats.

PMID- 17178212
TI  - Development of PCR primers based on a fragment from randomly amplified
      polymorphic DNA for the detection of Escherichia coli O157:H7/NM.
AB  - Serotype O157:H7 of EHEC is by far the most prevalent serotype associated with
      haemorrhagic colitis (HC) and haemolytic uremic syndrome (HUS). Although PCR
      methods aimed on the detection of genes associated with the pathogenicity of
      Escherichia coli O157:H7 have been reported, tests allowing the direct
      identification of this serotype are rare. In this study, we used RAPD-PCR tests
      to analyze strains of E. coli O157:H7 serotype, strains of non-pathogenic E.
      coli, and strains of other pathotypes, including enterotoxigenic E. coli (ETEC),
      enteropathogenic E. coli (EPEC), enteroinvasive E. coli (EIEC), and
      enteroaggregation E. coli (EAggEC). One RAPD fragment co-shared by serotype
      O157:H7 strains was observed when 10-mer primer termed as OPQ3 was used. After
      sequencing this fragment, three primers were designed and combined to form two
      PCR primer pairs. These two primer pairs were highly specific to the strains
      belonging to E. coli O157:H7/NM (non-motile).

PMID- 17178213
TI  - Idiotypic and anti-idiotypic elastin autoantibodies: Implications for IVIg and
      pregnancy loss.
AB  - PROBLEM: The aim of this study was to investigate anti-elastin and anti-anti
      elastin autoantibodies in intravenous immunoglobulin (IVIg) lots as an attempt to
      further explain the effect of IVIg in recurrent pregnancy loss (RPL). METHOD OF
      STUDY: Serum samples of 10 female patients with RPL and 10 healthy subjects were
      tested for anti-elastin autoantibodies and used in competitive inhibition
      studies. A total of 44 IVIg lots (ZLB Behring, Switzerland) were tested for anti
      elastin and anti-anti-elastin idiotypes. One way analysis of variance (ANOVA) and
      Least Significant Difference (LSD method) were used for statistical analysis of
      differences between the lots. RESULTS: Serum anti-elastin IgG autoantibodies were
      significantly higher in the study group, compared to the controls. In all lots
      anti-elastin IgG antibodies were identified. All lots (except two of them) showed
      similar dose-dependent inhibition of serum anti-elastin activity by anti-elastin
      anti-idiotypes in IVIg. CONCLUSIONS: Anti-elastin IgG autoantibodies were
      increased in patients with RPL - a finding which needs further explanation. Anti
      elastin and anti-anti-elastin idiotypes were identified in different IVIg lots.
      The presence in IVIg of anti-idiotypes against anti-elastin autoantibodies from
      patients' sera could be an additional mechanism of the beneficial effect of IVIg
      in reproductive failure.

PMID- 17178214
TI  - The premorbid adjustment scale structured interview (PAS-SI): preliminary
      findings.
AB  - BACKGROUND: The Premorbid Adjustment Scale (PAS) is a widely used rating scale to
      assess premorbid functioning retrospectively. Despite its widespread use there is
      no published structured interview (SI) schedule and little is known about the
      reliability of the instrument. OBJECTIVE: To design and test the reliability of a
      structured interview schedule for the PAS, the PAS-SI, across different cultures.
      METHODS: Starting from PAS items and response options, questions were prepared
      that lead to a response option. Instructions to skip certain items, for example,
      quality of friendships after a person noted no friends, were provided. Additional
      instructions were prepared including guidelines to determine the first onset of
      psychotic symptoms thereby ensuring that the interview is only directed to
      premorbid functioning. The interview was translated from English into Hebrew,
      Portuguese, French, Dutch (Flemish), Turkish, Italian, Lithuanian, Greek,
      Russian, Ukrainian, and Romanian and tested for inter-rater reliability "in nine
      of these languages". Eighty-four psychiatrists from 10 different countries acted
      as raters in a role-play assisted training session after which they rated the PAS
      SI in their native language. The intra-class correlation was computed to index
      reliability. RESULTS: The weighted intra-class correlation for absolute agreement
      and consistency was .77. CONCLUSIONS: The PAS-SI provides reliable and consistent
      data on premorbid functioning.

PMID- 17178215
TI  - TWEAK inhibits TGF-beta-induced contraction of normal and keloid fibroblast
      embedded collagen gel.

PMID- 17178216
TI  - Amelioration of benzo (a) pyrene-induced lung carcinogenesis in strain A mice by
      diphenylmethyl selenocyanate.
AB  - Organoselenocyanates are an important class of chemopreventive agents, which
      possess antioxidative, antimutagenic and anticarcinogenic properties. In the
      present study, we used benzo (a) pyrene (BP)-induced lung carcinogenesis model
      for assessment of the chemopreventive efficacy of diphenylmethyl selenocyanate, a
      synthetic organoselenocyanate. BP was given at a dose of 0.2mg/mouse to initiate
      lung carcinogenesis in strain A mouse and the Se compound was given orally at a
      dose of 3mg/kgb.w. Histopathological characterizations and biochemical estimation
      were done to determine the protective effect of Se compound during the
      progression of lung carcinogenesis. Hyperplasia and severe dysplasia, the
      precancerous stage, were evident in carcinogen control group after 8th and 22nd
      week, respectively. These times were selected as the targets for chemoprevention.
      Treatment with the Se compound effectively reduced the incidence of hyperplasia
      and severe dysplasia. The Se compound also significantly (p<0.01) reduced
      microsomal lipid peroxidation and induced glutathione-S-transferase activity in
      liver and lung when measured after 8th and 22nd week. Lung cancer is diagnosed in
      majority of cases only at a later stage. These findings will further strengthen
      the view on organoselenocyanate as an effective cancer chemopreventive agent
      against lung carcinogenesis when applied at the post-initiation phase.

PMID- 17178217
TI  - A proof of concept study to evaluate stepping down the dose of fluticasone in
      combination with salmeterol and tiotropium in severe persistent asthma.
AB  - We conducted a double blind, randomised, placebo-controlled, crossover study
      evaluating the effects of halving inhaled steroid dosage plus salmeterol, or
      salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean
      FEV(1) 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000
      microg daily, and were subsequently randomised to 4 weeks of either (a) HFA
      fluticasone propionate 500 microg BD/salmeterol 100 microg BD/HFA-tiotropium
      bromide18 microg od; or (b) fluticasone propionate 500 microg BD/salmeterol 100
      microg BD matched placebo. Measurements of spirometry and body plethysmography
      were made. Adding salmeterol to half the dose of fluticasone led to a mean
      improvement (95% CI) vs. baseline in morning PEF of 41.5 (14.0-69.0)l/min
      [p<0.05]; and RAW of 0.98 (0.14-1.8)cm H(2)O/l/s [p<0.05]. Adding
      salmeterol/tiotropium produced similar improvements in PEF and RAW, but also
      improved FEV(1) by 0.17 (0.01-0.32)l [p<0.05]; FVC 0.24 (0.05-0.43)l [p<0.05] and
      reduced exhaled NO by 2.86 (0.12-5.6)ppb [p<0.05]. RV and TLC were not altered by
      either treatment; there were no significant changes in symptoms or quality of
      life compared with baseline. Addition of salmeterol/tiotropium to half the dose
      of fluticasone afforded small, but significant improvements in pulmonary
      function. These effects were not associated with commensurate changes in
      subjective symptoms or quality of life.

PMID- 17178218
TI  - Coupled waveguide-surface plasmon resonance biosensor with subwavelength grating.
AB  - This study develops a coupled waveguide-surface plasmon resonance (CWSPR)
      biosensor with a subwavelength grating structure for the real-time analysis of
      biomolecular interactions. In the proposed optical metrology system, normally
      incident white light is coupled into the waveguide layer through the
      subwavelength grating structure thereby enhancing the wave vector which excites
      the surface plasmons on the metal sensing surface. The proposed CWSPR biosensor
      not only retains the same sensing sensitivity as that of a conventional surface
      plasmon resonance device, but also yields a sharper dip in the reflectivity
      spectrum and therefore provides an improved measurement precision. Moreover, the
      metrology setup overcomes the limitations of the conventional Kretschmann
      attenuated total reflection approach and is less sensitive to slight variations
      in the angle of the incident light. The experimental results confirm that the
      current CWSPR biosensor provides a straightforward yet powerful technique for
      real-time biomolecular interaction analysis.

PMID- 17178219
TI  - An electrochemical approach to monitor pH change in agar media during plant
      tissue culture.
AB  - In this work, metal oxide microelectrodes were developed to monitor pH change in
      agar media during plant tissue culture. An antimony wire was produced by a new
      approach "capillary melt method". The surface of the obtained antimony wire was
      oxidized in a potassium nitrate melt to fabricate an antimony oxide film for pH
      sensing. Characterization results show that the oxide layer grown on the wire
      surface consists of Sb(2)O(3) crystal phase. The sensing response, open-circuit
      potential, of the electrode has a good linear relationship (R(2)=1.00) with pH
      value of the test solution. Adding organic compounds into the test media would
      not affect the linear relationship, although the slope of the lines varied with
      different ingredients added. The antimony oxide electrodes were employed to
      continuously monitor pH change of agar culture media during a 2-week plant tissue
      culture of Dendrobium candidum. The antimony oxide electrode fabricated this way
      has the advantages of low cost, easy fabrication, fast response, and almost no
      contamination introduced into the system. It would be suitable for in situ and
      continuous pH measurement in many bio applications.

PMID- 17178220
TI  - Identification of arylsulfonamides as Aquaporin 4 inhibitors.
AB  - Carbonic anhydrase inhibitors AZA, EZA, and 4-acetamidobenzsulfonamide were found
      to inhibit human AQP4-M23 mediated water transport by 80%, 68%, and 23%,
      respectively, at 20 microM in an in vitro functional assay. AZA was found to have
      an IC50 against AQP4 of 0.9 microM. Phloretin was inactive under the same
      conditions.

PMID- 17178221
TI  - Amino acid-based enantiomerically pure 3-substituted 1,4-benzodiazepin-2-ones: a
      new class of anti-ischemic agents.
AB  - A series of 3-substituted 1,4-benzodiazepin-2-ones derived from S and R amino
      acids were evaluated for their anti-ischemic activity in vitro. Treatment with
      compounds 7h, 16, 9d, and 17 decreased the apoptotic neuronal number, however
      increased the neuronal viability. The compounds decreasing apoptosis could
      protect neurons from the ischemic injury. The difference in the activities of 1,4
      benzodiazepin-2-ones derived from S- and R-amino acids is discussed and explained
      on the basis of molecular modeling studies.

PMID- 17178222
TI  - Quinazoline and benzimidazole MCH-1R antagonists.
AB  - We have modified the previously reported 2-aminoquinoline 1 to provide two novel
      series of MCH-1R antagonists. Representative compounds from the quinazoline and
      benzimidazole series have been shown to be potent and selective, with promising
      in vitro eADME profiles.

PMID- 17178223
TI  - Novel antiproliferative analogs of the Taq DNA polymerase inhibitor catalpol.
AB  - The naturally occurring iridoid catalpol (1) is a Taq DNA polymerase inhibitor.
      However, its poor lipophilicity might account for the lack of biological activity
      against human solid tumor cell lines. The traditional prodrug approach by means
      of peracetylation of the free hydroxyl groups led to a compound, which showed a
      marginal growth inhibition against the most sensitive cell line A2780 (ovarian
      cancer). However, the formation of analogs bearing one to three silyl ether
      groups led to antiproliferative compounds against a panel of six human solid
      tumor cell lines, with GI50 values in the range 1.8-4.8 microM. Cell cycle
      studies revealed arrest in G0/G1 phase that is consistent with DNA polymerase
      inhibition.

PMID- 17178224
TI  - 3-Hydroxychromones as cyclin-dependent kinase inhibitors: synthesis and
      biological evaluation.
AB  - A novel series of 3-hydroxychromones were prepared and found to be CDK
      inhibitors. Isothiazolidine 1,1-dioxide analogues showed potent CDK1 and CDK2
      inhibitory activities and inhibited proliferation of EJ, HCT116, SW620, and
      MDAMB468 cancer cells.

PMID- 17178225
TI  - Nonproliferative epithelial alteration and expression of estrogen receptor and
      Ki67 in the contralateral breast of women treated with tamoxifen for breast
      cancer.
AB  - The aim of study was to evaluate the frequency of nonproliferative epithelial
      alteration and expression of Ki67 and estrogen receptors (ER) in patients using
      tamoxifen. Forty-four women were selected who had been taking 20mg of tamoxifen
      daily for at least 12 months for adjuvant treatment of breast cancer. The women
      underwent core biopsy in the contralateral breast into an area of highest
      fibroglandular mammographic density. Fragments were analyzed by
      immunohistochemistry for monoclonal antibody Ki67 and ER, and histopathologic
      analysis. It was verified that 82% of the patients presented nonproliferative
      epithelial alteration, 70% were ER-negative, and all had low Ki67 expression.
      There was no association between duration of tamoxifen therapy, patient age,
      mammographic density, and presence of nonproliferative alteration (P>0.05). In
      conclusion, tamoxifen for more than a year showed a high frequency of
      nonproliferative epithelial alteration and low expression of Ki67 and ER in the
      normal breast tissue, consistent with low cell proliferation.

PMID- 17178226
TI  - Discovery of a new insecticide lead by optimizing a target-diverse scaffold:
      tetrazolinone derivatives.
AB  - In order to discover lead compounds with novel action mechanism, a series of
      tetrazolinone derivatives bearing structurally diverse substituents, 1-aryl-4
      substituted-1,4-di-hydro-5H-tetrazol-5-ones 2, 1-((5-(alkylthio)-1,3,4-oxadiazol
      2-yl)methyl)-4-(substituted)- phenyl-1H-tetrazol-5(4H)-ones 5, and 1-((5
      (alkylthio)-1,3,4-thiadiazol-2-yl)methyl)-4- (substituted)phenyl-1H-tetrazol
      5(4H)-ones 7, were designed and synthesized in good yields by a multiple-step
      synthetic procedure. The results of greenhouse in vivo test indicated that all
      the target compounds did not displayed herbicidal activity, however, some of them
      exhibited excellent in vivo insecticidal activity against Tetranychus
      cinnabarinus at the concentration of 250 mg L-1. To our knowledge, this is the
      first report about the insecticidal activity of tetrazolinone derivatives, which
      indicated that the tetrazolinone scaffold could be identified as a novel
      insecticidal lead structure. The present work demonstrated that optimizing a
      target-diverse scaffold is an effective way to discover new lead compounds with
      new action mechanism or biological activity.

PMID- 17178227
TI  - Design, synthesis, and evaluation of 2-aryl-3-heteroaryl-1,3-thiazolidin-4-ones
      as anti-HIV agents.
AB  - Compounds having isothiourea or thiourea functional group have shown high anti
      HIV-1 activity. Therefore, a series of 2-aryl-3-heteroaryl-1,3-thiazolidin-4-ones
      were designed, synthesized, and evaluated for anti-HIV-1 RT activity. The results
      of in vitro tests showed that the compound 9 exhibited EC50 at 0.26 microM with
      minimal toxicity in MT-4 cells as compared to 0.35 microM for thiazobenzimidazole
      (TBZ). It may be inferred from the present data that majority of compounds in
      this series exhibit higher selectivity index than TBZ.

PMID- 17178228
TI  - The synthesis of amphipathic prodrugs of 1,2-diol drugs with saccharide
      conjugates by high regioselective enzymatic protocol.
AB  - A facile, high regioselective enzymatic synthesis approach for the preparation of
      amphipathic prodrugs with saccharides of mephenesin and chlorphenesin was
      developed. Firstly, transesterification of two drugs with divinyl dicarboxylates
      with different carbon chain length was performed under the catalysis of Candida
      antarctica lipase acrylic resin and Lipozyme in anhydrous acetone at 50 degrees
      C, respectively. A series of lipophilic derivatives with vinyl groups of
      mephenesin and chlorphenesin were prepared. The influences of different organic
      solvents, enzyme sources, reaction time, and the acylation reagents on the
      synthesis of vinyl esters were investigated. And then, protease-catalyzed high
      regioselective acylation of D-glucose and D-mannose with vinyl esters of
      mephenesin and chlorphenesin gave drug-saccharide derivatives in good yields. The
      studies of lipophilicity and hydrolysis in vitro of prodrugs verified that drug
      saccharide derivatives had amphipathic properties, and both lipophilic and
      amphipathic drug derivatives had obvious controlled release characteristics.

PMID- 17178229
TI  - An unusual complication of a ventricular pace maker electrode.

PMID- 17178230
TI  - Mediastinal tumor?--Gibson-Mikulicz tampon.

PMID- 17178231
TI  - Unusual retained foreign body in the lung: a tree branch.

PMID- 17178232
TI  - Social trust, firearm prevalence, and homicide.
AB  - PURPOSE: Past research suggests that Americans arm themselves when they do not
      trust one another. We reexamine the relationship between social trust and firearm
      prevalence with improved data and methods. We also control for conditions,
      including area homicide rates, that other research showed to be related to both
      social trust and firearm prevalence. METHODS: We use structural equation models
      to assess reciprocal effects of social trust, firearm prevalence, and homicide
      rates for a nationally representative sample of counties and county clusters (n =
      99). RESULTS: We found no direct relationship between social trust and firearm
      prevalence. Social trust is related to firearm prevalence indirectly through its
      influence on homicide rates. Areas with low levels of social trust have high
      homicide rates, which, in turn, increase firearm prevalence. CONCLUSIONS:
      Americans arm themselves in response to high levels of firearm violence. Because
      greater social trust is related to lower homicide rates, public health
      researchers should be concerned with the community conditions that promote social
      trust.

PMID- 17178233
TI  - Utility of proxy versus index respondent information in a population-based case
      control study of rapidly fatal cancers.
AB  - PURPOSE: This work provides an empirical assessment of the usefulness of
      obtaining exposure data from proxy respondents. METHODS: Two independent case
      groups were formed in data from a population-based case-control study. One case
      set was derived from proxy respondents. The second case series was derived from
      respondents who self-reported. The second case group was matched to the proxy
      case group for age, cancer site, and sex. These data were compared with a control
      group for completeness of information and identifying heterogeneity of risk
      estimates for a variety of variables. Index cases and controls were matched to
      the 829 available proxy respondents for sex, age (5-year groups), and cancer
      site. RESULTS: Proxy respondents provided levels of complete information similar
      to index cases and controls for height and weight; occupational physical
      activity; consumption of coffee, alcohol, and cigarettes; and family history of
      cancer. Proxies had more missing responses for variables concerning recreational
      physical activity, clinical depression, age at first menstruation, use of oral
      contraceptives, and occupational exposure to pesticides. Polytomous logistic
      regression models found only a few examples of meaningful heterogeneity among all
      variables, limited to models for coffee consumption and cigarette smoking.
      CONCLUSIONS: Our data suggest that proxy respondents, especially parents and
      spouses, provide adequately complete information for many, but not all, exposures
      common in epidemiologic studies.

PMID- 17178234
TI  - Anatomically constrained region deformation for the automated segmentation of the
      hippocampus and the amygdala: Method and validation on controls and patients with
      Alzheimer's disease.
AB  - We describe a new algorithm for the automated segmentation of the hippocampus
      (Hc) and the amygdala (Am) in clinical Magnetic Resonance Imaging (MRI) scans.
      Based on homotopically deforming regions, our iterative approach allows the
      simultaneous extraction of both structures, by means of dual competitive growth.
      One of the most original features of our approach is the deformation constraint
      based on prior knowledge of anatomical features that are automatically retrieved
      from the MRI data. The only manual intervention consists of the definition of a
      bounding box and positioning of two seeds; total execution time for the two
      structures is between 5 and 7 min including initialisation. The method is
      evaluated on 16 young healthy subjects and 8 patients with Alzheimer's disease
      (AD) for whom the atrophy ranged from limited to severe. Three aspects of the
      performances are characterised for validating the method: accuracy (automated vs.
      manual segmentations), reproducibility of the automated segmentation and
      reproducibility of the manual segmentation. For 16 young healthy subjects,
      accuracy is characterised by mean relative volume error/overlap/maximal boundary
      distance of 7%/84%/4.5 mm for Hc and 12%/81%/3.9 mm for Am; for 8 Alzheimer's
      disease patients, it is 9%/84%/6.5 mm for Hc and 15%/76%/4.5 mm for Am. We
      conclude that the performance of this new approach in data from healthy and
      diseased subjects in terms of segmentation quality, reproducibility and time
      efficiency compares favourably with that of previously published manual and
      automated segmentation methods. The proposed approach provides a new framework
      for further developments in quantitative analyses of the pathological hippocampus
      and amygdala in MRI scans.

PMID- 17178235
TI  - A simultaneous EEG-fMRI study of painful electric stimulation.
AB  - Together with a detailed behavioral analysis, simultaneous measurement of
      functional magnetic resonance imaging (fMRI) and electroencephalography (EEG)
      permits a better elucidation of cortical pain processing. We applied painful
      electrical stimulation to 6 healthy subjects and acquired fMRI simultaneously
      with an EEG measurement. The subjects rated various stimulus properties and the
      individual affective state. Stimulus-correlated BOLD effects were found in the
      primary and secondary somatosensory areas (SI and SII), the operculum, the
      insula, the supplementary motor area (SMA proper), the cerebellum, and posterior
      parts of the anterior cingulate gyrus (ACC). Perceived pain intensity was
      positively correlated with activation in these areas. Higher unpleasantness
      rating was associated with suppression of activity in areas known to be involved
      in stimulus categorization and representation (ventral premotor cortex, PCC,
      parietal operculum, insula) and enhanced activation in areas initiating,
      propagating, and executing motor reactions (ACC, SMA proper, cerebellum, primary
      motor cortex). Concordant dipole localizations in SI and ACC were modeled. Using
      the dipole strength in SI, the network was restricted to SI. The BOLD signal
      change in ACC was positively correlated to the individual dipole strength of the
      source in ACC thus revealing a close relationship of BOLD signal and possibly
      underlying neuronal electrical activity in SI and the ACC. The BOLD signal change
      decreased in SI over time. Dipole strength of the ACC source decreased over the
      experiment and increased during the stimulation block suggesting sensitization
      and habituation effects in these areas.

PMID- 17178236
TI  - Functional dissociations in top-down control dependent neural repetition priming.
AB  - Little is known about the neural mechanisms underlying top-down control of
      repetition priming. Here, we use functional brain imaging to investigate these
      mechanisms. Study and repetition tasks used a natural/man-made forced choice
      task. In the study phase subjects were required to respond to either pictures or
      words that were presented superimposed on each other. In the repetition phase
      only words were presented that were new, previously attended or ignored, or
      picture names that were derived from previously attended or ignored pictures.
      Relative to new words we found repetition priming for previously attended words.
      Previously ignored words showed a reduced priming effect, and there was no
      significant priming for pictures repeated as picture names. Brain imaging data
      showed that neural priming of words in the left prefrontal cortex (LIPFC) and
      left fusiform gyrus (LOTC) was affected by attention, semantic compatibility of
      superimposed stimuli during study and cross-modal priming. Neural priming reduced
      for words in the LIPFC and for words and pictures in the LOTC if stimuli were
      previously ignored. Previously ignored words that were semantically incompatible
      with a superimposed picture during study induce increased neural priming compared
      to semantically compatible ignored words (LIPFC) and decreased neural priming of
      previously attended pictures (LOTC). In summary, top-down control induces
      dissociable effects on neural priming by attention, cross-modal priming and
      semantic compatibility in a way that was not evident from behavioral results.

PMID- 17178237
TI  - Dostoevsky's epilepsy: A contemporary "paleodiagnosis".

PMID- 17178238
TI  - Antitumor effects of cationic synthetic peptides derived from Lys49 phospholipase
      A2 homologues of snake venoms.
AB  - The effects of two cationic synthetic peptides, derived from the C-terminal
      region of Lys49 phospholipase A2 homologues from snake venoms, upon various
      murine tumor cell lines (B16 melanoma, EMT6 mammary carcinoma, S-180 sarcoma, P3X
      myeloma, tEnd endothelial cells) were evaluated. The peptides are 13-mers derived
      from Agkistrodon piscivorus piscivorus Lys49 PLA2 (p-AppK: KKYKAYFKLKCKK) and
      Bothrops asper Lys49 myotoxin II (pEM-2[D]: KKWRWWLKALAKK), respectively, in the
      latter case with slight modifications and with all-D amino acids. All tumor cells
      tested were susceptible to the lytic action of the peptides. The susceptibility
      of tumor cell lines was not higher than that of C2C12 skeletal muscle myoblasts,
      utilized as a non-transformed cell line control. However, in a murine model of
      subcutaneous solid tumor growth of EMT6 mammary carcinoma, the intraperitoneal
      administration of pEM-2[D] caused a tumor mass reduction of 36% (p<0.05), which
      was of similar magnitude to that achieved by the administration of paclitaxel, an
      antitumor drug in clinical use. Thus, the C-terminal peptides of Lys49
      phospholipase A2 homologues present antitumor effects that might be of interest
      in developing therapeutic strategies against cancer.

PMID- 17178239
TI  - Neural representations during sleep: from sensory processing to memory traces.
AB  - In the course of a day, the brain undergoes large-scale changes in functional
      modes, from attentive wakefulness to the deepest stage of sleep. The present
      paper evaluates how these state changes affect the neural bases of sensory and
      cognitive representations. Are organized neural representations still maintained
      during sleep? In other words, despite the absence of conscious awareness, do
      neuronal signals emitted during sleep contain information and have a functional
      relevance? Through a critical evaluation of the animal and human literature,
      neural representations at different levels of integration (from the most
      elementary sensory level to the most cognitive one) are reviewed. Recordings of
      neuronal activity in animals at presentation of neutral or significant stimuli
      show that some analysis of the external word remains possible during sleep,
      allowing recognition of behaviorally relevant stimuli. Event-related brain
      potentials in humans confirm the preservation of some sensory integration and
      discriminative capacity. Behavioral and neuroimaging studies in humans
      substantiate the notion that memory representations are reactivated and are
      reorganized during post-learning sleep; these reorganisations may account for the
      beneficial effects of sleep on behavioral performance. Electrophysiological
      results showing replay of neuronal sequences in animals are presented, and their
      relevance as neuronal correlates of memory reactivation is discussed. The
      reviewed literature provides converging evidence that structured neural
      representations can be activated during sleep. Which reorganizations unique to
      sleep benefit memory representations, and to what extent the operations still
      efficient in processing environmental information during sleep are similar to
      those underlying the non-conscious, automatic processing continually at work in
      wakefulness, are challenging questions open to investigation.

PMID- 17178241
TI  - TRPM channels, calcium and redox sensors during innate immune responses.
AB  - Melastatin-related TRPM ion channels have emerged as novel therapeutic targets
      due to their potential ability to modulate the function and fate of immune cells
      during inflammation, innate, and adaptive immunity. Four family members, TRPM1,
      TRPM2, TRPM4 and TRPM7 have a strong presence in the immune system. TRPM channels
      regulate ion-homeostasis by sensing cellular redox status and cytoplasmic calcium
      levels. TRPM2 for example, is highly expressed in phagocytes. This channel is
      activated by intracellular ADP-ribose upon exposure to oxidative stress and
      induces cell death. Here we will review the functional links between TRPM
      mediated ion conductance, chemotaxis, apoptosis, and innate immunity.

PMID- 17178240
TI  - Cholinergic modulation of Pavlovian fear conditioning in rats: differential
      effects of intrahippocampal infusion of mecamylamine and methyllycaconitine.
AB  - The cholinergic system has consistently been implicated in Pavlovian fear
      conditioning. Considerable work has been done to localize specific nicotinic
      receptor subtypes in the hippocampus and determine their functional importance;
      however, the specific function of many of these subtypes has yet to be
      determined. An alpha7 nicotinic antagonist methyllycaconitine (MLA) (35 microg),
      and a broad spectrum non-alpha7 nicotinic antagonist mecamylamine (35 microg) was
      injected directly into the dorsal hippocampus or overlying cortex either 15 min
      pre-, 1 min post-, or 6h post-fear conditioning. One week after conditioning,
      retention of contextual and cue (tone) conditioning were assessed. A significant
      impairment in retention of contextual fear was observed when mecamylamine was
      injected 15 min pre- and 1 min post-conditioning. No significant impairment was
      observed when mecamylamine was injected 6h post-conditioning. Likewise, a
      significant impairment in retention of contextual fear was observed when MLA was
      injected 1 min post-conditioning; however, in contrast, MLA did not show any
      significant impairments when injected 15 min pre-conditioning, but did show a
      significant impairment when injected 6h post-conditioning. There were no
      significant impairments observed when either drug was injected into overlying
      cortex. No significant impairments were observed in cue conditioning for either
      drug. In general, specific temporal dynamics involved in nicotinic receptor
      function were found relative to time of receptor dysfunction. The results
      indicate that the greatest deficits in long-term retention (1 week) of contextual
      fear are produced by central infusion of MLA minutes to hours post-conditioning
      or mecamylamine within minutes of conditioning.

PMID- 17178242
TI  - Genetic pathways to mammalian heart development: Recent progress from
      manipulation of the mouse genome.
AB  - Mammalian heart development requires multiple genetic networks, only some of
      which are becoming known in all their complexity. Substantial new information has
      become available thanks to an expanding toolkit that offers more and more mouse
      gene manipulation options, and that is taking the mouse closer to more powerful
      invertebrate genetic models. We review examples of recent data with a cardiac
      lineage-based view of heart development, especially outflow tract and right
      ventricle. The medical significance of these studies is not only relevant to
      congenital heart disease, but also to the biology of cardiac cell regeneration.

PMID- 17178244
TI  - Mating-type genes and the genetic structure of a world-wide collection of the
      tomato pathogen Cladosporium fulvum.
AB  - Two mating-type genes, designated MAT1-1-1 and MAT1-2-1, were cloned and
      sequenced from the presumed asexual ascomycete Cladosporium fulvum (syn.
      Passalora fulva). The encoded products are highly homologous to mating-type
      proteins from members of the Mycosphaerellaceae, such as Mycosphaerella
      graminicola and Cercospora beticola. In addition, the two MAT idiomorphs of C.
      fulvum showed regions of homology and each contained one additional putative ORF
      without significant similarity to known sequences. The distribution of the two
      mating-type genes in a world-wide collection of 86 C. fulvum strains showed a
      departure from a 1:1 ratio (chi(2)=4.81, df=1). AFLP analysis revealed a high
      level of genotypic diversity, while strains of the fungus were identified with
      similar virulence spectra but distinct AFLP patterns and opposite mating-types.
      These features could suggest the occurrence of recombination in C. fulvum.

PMID- 17178245
TI  - The key enzyme in galactose metabolism, UDP-galactose-4-epimerase, affects cell
      wall integrity and morphology in Candida albicans even in the absence of
      galactose.
AB  - The enzyme UDP-galactose-4-epimerase (GAL10) catalyzes a key step in galactose
      metabolism converting UDP-galactose to UDP-glucose which then can get metabolized
      through glycolysis and TCA cycle thus allowing the cell to use galactose as a
      carbon and energy source. As in many fungi, a functional homolog of GAL10 exists
      in Candida albicans. The domainal organization of the homologs from Saccharomyces
      cerevisiae and C. albicans show high degree of homology having both mutarotase
      and an epimerase domain. The former is responsible for the conversion of beta-d
      galactose to alpha-d-galactose and the latter for epimerization of UDP-galactose
      to UDP-glucose. Absence of C. albicans GAL10 (CaGAL10) affects cell-wall
      organization, oxidative stress response, biofilm formation and filamentation.
      Cagal10 mutant cells tend to flocculate extensively as compared to the wild-type
      cells. The excessive filamentation in this mutant is reflected in its irregular
      and wrinkled colony morphology. Cagal10 strain is more susceptible to oxidative
      stress when tested in presence of H2O2. While the S. cerevisiae GAL10 (ScGAL10),
      essential for survival in the presence of galactose, has not been reported to
      have defects in the absence of galactose, the C. albicans homolog shows these
      phenotypes during growth in the absence of galactose. Thus a functional CaGal10
      is required not only for galactose metabolism but also for normal hyphal
      morphogenesis, colony morphology, maintenance of cell-wall integrity and for
      resistance to oxidative stress even in the absence of galactose.

PMID- 17178246
TI  - Function analysis of steA homolog in Aspergillus oryzae.
AB  - The asexual ascomycete Aspergillus oryzae has an steA homolog in its genome. The
      steA homolog of A. oryzae was transcribed in the wild-type strain but steA
      disruption did not affect the phenotype of the disruptant strain. On the other
      hand, the steA-overexpressing strain showed the restriction of vegetative hyphal
      growth and conidiation, and the formation of balloon-shaped structures. The
      restriction of vegetative hyphal growth and conidiation were partially rescued by
      high osmolarity. In addition, the hyphal growth of the steA-overexpressing strain
      was inhibited by Calcofluor white, and the strain was found to be sensitive to
      cell-wall-degrading reagents. Increase of secretory cell-wall-degrading enzymes
      of the steA-overexpressing strain was detected. These results indicate that SteA
      regulates cell-wall-degrading enzymes and that the phenotypes of A. oryzae steA
      overexpressing strain may be due to cell wall abnormalities. steA may participate
      in cell wall metabolism.

PMID- 17178247
TI  - Deletion of the adenylate cyclase (sac1) gene affects multiple developmental
      pathways and pathogenicity in Sclerotinia sclerotiorum.
AB  - Sclerotinia sclerotiorum, a broad host range plant pathogen, produces pigmented,
      multihyphal sclerotia that are capable of long-term survival. Under favorable
      conditions, sclerotia carpogenically germinate to give rise to apothecia and
      forcibly discharged ascospores which serve as the primary source of inoculum in
      the disease cycle. The molecular regulator(s) of sclerotial development in
      filamentous fungi are largely unknown; however, pharmacological data has revealed
      that cyclic AMP (cAMP) negatively regulates sclerotial biogenesis in S.
      sclerotiorum. Based on this observation, we analyzed the role of cAMP by deleting
      the single copy adenylate cyclase (AC) sac1 gene from S. sclerotiorum. In
      culture, cyclic AMP levels in the knock-out (KO1) strain were greatly reduced
      compared to wild type, the hyphal branching pattern was altered, microconidia
      (spermatia) were more abundant, and aberrant sclerotia were produced in a
      concentric pattern. The KO1 strain was pathogenic on mechanically wounded
      tissues; however, virulence was severely attenuated. The pathogenicity defect on
      unwounded leaves is attributed to the absence of infection cushions and the
      attenuated virulence on wounded leaves correlates with the slow growth rate
      observed in culture. This study presents the first description of an adenylate
      cyclase mutant that affects both pathogenicity and sclerotial development in a
      broad host range necrotroph.

PMID- 17178249
TI  - Prevention of lysosomal storage disorders in Israel.
AB  - Prevention programs for the detection of heterozygotes of relatively prevalent
      autosomal recessive diseases in various ethnic groups are available in recent
      years in Israel. Several lysosomal storage disorders (LSD) are included in this
      program. The goal of the program is the ascertainment of high risk couples before
      the birth of affected offspring. This is performed by a population screening
      program that addresses the specific needs and requirements of various population
      groups in Israel. The programs are supervised and designed by medical/clinical
      geneticists and are accompanied by genetic counseling prior to and after testing.
      Three types of population screening programs are in operation. The first type is
      offered to the general population and is directed to premarital and married
      couples. High risk families mostly opt for prenatal diagnosis. The second type is
      performed for diseases with a frequency of about 1:1000. This occurrence is
      common in Israel only in various Arab communities due to the high rate of
      consanguinity. The third type is a premarital screening performed by the Orthodox
      Jewish community and is operated by a nonprofit organization--"Dor Yeshorim". Two
      heterozygotes for a particular disease are advised not to proceed with the
      marriage and thus avoid the dilemma of prenatal diagnosis. Founder mutations of
      the relevant genes for each ethnic group are tested and the testing is tailored
      for each individual according to his/her ethnic background. Genetic counseling
      presents family planning options to high risk couples. These programs have
      resulted in a significant reduction in the birth of affected patients of the
      tested LSD a well as other recessive diseases in recent years.

PMID- 17178248
TI  - Treatment of epilepsy in Rett syndrome.
AB  - INTRODUCTION: Epilepsy is very frequent in Rett syndrome (RTT) patients and often
      difficult to treat. Because most cases of RTT are caused by mutations in the
      MECP2 gene it is reasonable to assume that convulsions are based on common
      pathogenetic mechanisms and thus should have a similar response to antiepileptic
      drugs. PURPOSE: To find the optimal treatment for epilepsy in RTT. METHODS: We
      performed a retrospective study on 110 female patients with confirmed MECP2
      mutations. RESULTS: The median age was 10 years, 58% had a history of epilepsy
      and 55% received antiepileptic drugs (AEDs). Only sulthiame, carbamazepine and
      valproate were administered in an adequate frequency to allow statistical
      analysis. The best anticonvulsive results were seen in the RTT group that was
      treated with carbamazepine. Sulthiame was slightly less effective while valproate
      was significantly less effective. The rate of side effects was equivalent in all
      groups. In conclusion, carbamazepine should be recommended as first choice AED in
      RTT. If carbamazepine is not effective or not well tolerated sulthiame ought to
      be taken as second choice AED.

PMID- 17178250
TI  - The functions of RPS19 and their relationship to Diamond-Blackfan anemia: a
      review.
AB  - The relatively new study of ribosomal proteins has allowed for greater
      understanding of protein synthesis; however the connection between ribosomal
      proteins' roles and that of disease pathophysiology has not yet been established.
      RPS19 is a ribosomal protein linked to Diamond-Blackfan anemia whose functions
      have begun to be elucidated. We review here the known roles of RPS19 in both
      ribosome construction and other extra-ribosomal functions and discuss their
      relationship to Diamond-Blackfan anemia.

PMID- 17178251
TI  - Beyond "Landscapes of Despair": the need for new research on the urban
      environment, sprawl, and the community integration of persons with severe mental
      illness.
AB  - The purpose of this commentary is to discuss important trends in the housing of
      people with severe mental illness in the past 20 years that require the attention
      of mental health geographers and other experts on the effects of place on mental
      health. Issues that are worthy of consideration in new research include:
      assessing the impact of place effects on community integration, the impact of
      sprawl, and the emergence of the independent scatter-site housing model. Possible
      implications of these trends for the effects of place on people with severe
      mental illness are discussed.

PMID- 17178253
TI  - Cytogenetic damage in workers from a coal-fired power plant.
AB  - The aim of this study was to investigate the genotoxic risk to workers
      occupationally exposed to coal combustion products in Afsin-Elbistan A power
      plant, located in south-eastern Turkey. We analysed chromosomal aberrations
      (CAs), polyploidy, sister-chromatid exchanges (SCEs), and micronuclei (MN) in 48
      male workers without a history of smoking, tobacco chewing, or alcohol
      consumption. The results were compared with a control group of 30 healthy male
      individuals without exposure to any known genotoxic agents. The mean frequencies
      of CA, polyploidy, SCEs (P<0.01), and MN (P<0.05) were significantly higher in
      workers than in the control group, by the Mann-Whitney U-test. Spearman's rho
      correlation analysis revealed a significant increase in the frequency of CA and
      MN with increasing years of exposure (P<0.05). However, there was no significant
      effect of age on the cytogenetic markers analysed in both groups (P>0.05). The
      data obtained from this study clearly showed chromosomal hazard in the peripheral
      lymphocytes of workers exposed to coal combustion products in Afsin-Elbistan A
      power plant for several years. This cytogenetic damage might be attributed to the
      cumulative effects of several substances due to chemical complexity of the coal
      ash and gaseous emissions rather than a specific substance.

PMID- 17178252
TI  - Initial comfort of lotrafilcon A silicone hydrogel contact lenses versus
      etafilcon A contact lenses for extended wear.
AB  - PURPOSE: To compare the initial comfort afforded by silicone hydrogel lenses
      (lotrafilcon A) versus the comfort afforded by conventional hydrogel lenses
      (etafilcon A) in extended wear (EW). DESIGN: Prospective, double-masked and
      randomized controlled trial. METHODS: Lotrafilcon A and etafilcon A contact
      lenses were eye randomly fitted on an EW basis for 7 days and nights in 20
      subjects. A forced-choice subject preference questionnaire was made. Subjects
      were comfort, dryness, red eye and visual quality after night wear and at the end
      of the day. Subjective scored satisfaction (scale: 1-5) and lens preference were
      assessed. RESULTS: Lotrafilcon A proved more comfortable after night wear (60%,
      CI95% 38-82%) and at the end of the day (70%, CI95% 49-90%) than etafilcon A
      after night wear (10%, CI95% 0-23%, P<0.05) and at the end of the day (20%, CI95%
      2-38%, P<0.05). The feeling of dryness was more marked with etafilcon A after
      night wear (50%, CI95% 27-72%) and at the end of the day (50%, CI95% 27-72%) than
      it was with lotrafilcon A (15%, CI95% 0%-31%) after night wear (P>0.05) and at
      the end of the day (25%, CI95% 5%-44%, P<0.05). General satisfaction with the
      lotrafilcon A lens was 3.65 points (CI95% 3-4.2) and with etafilcon A 2.95 points
      (CI95% 2.5-3.3, P<0.05). Eighty percent (CI95% 62%-98%) of subjects preferred
      lotrafilcon A (P<0.05) for EW. CONCLUSIONS: In EW, lotrafilcon A contact lenses
      were more comfortable and led to less dryness after night wear and at the end of
      the day than etafilcon A contact lenses.

PMID- 17178254
TI  - Correlation of dendritic cell infiltration with active crypt inflammation in
      ulcerative colitis.
AB  - The aim of this study was to evaluate the histological localization and
      phenotypic characteristics of infiltrating dendritic cells (DCs) and to examine
      the relationship between the degree of DC infiltration and the severity of
      inflammation in the colonic mucosa in ulcerative colitis (UC). Also explored was
      the expression of macrophage inflammatory protein-3alpha (MIP-3alpha), and its
      receptor CC-chemokine receptor 6 (CCR6), to evaluate the significance of immature
      DCs in the crypt inflammation evident in UC. There was a significant positive
      correlation between the number of infiltrating DCs and the degree of crypt
      inflammation, mononuclear cell infiltration, crypt atrophy, and comprehensive
      active inflammation. No significant correlation between the number of S-100
      protein(+) cells and the severity of crypt atrophy was found. S-100 protein(+),
      MIP-3alpha(+), and CCR6(+) cells were frequently localized in or around the crypt
      with inflammation. MIP-3alpha(+) neutrophils and S-100 protein(+) CCR6(+) cells
      with dendritic morphology were detected in or around the crypt inflammation. Both
      S-100 protein(+) DCs and CCR6(+) cells were frequently clustered in the surface
      mucosa beneath the surface epithelium when the crypt was not inflamed. CD1a(+)
      Langerhans-cell-type DCs were not found in any of the tissues examined. These
      data indicate that DCs participate not only in chronic inflammation but also in
      active crypt inflammation.

PMID- 17178255
TI  - Pitavastatin inhibits lysophosphatidic acid-induced proliferation and monocyte
      chemoattractant protein-1 expression in aortic smooth muscle cells by suppressing
      Rac-1-mediated reactive oxygen species generation.
AB  - Lysophosphatidic acid (LPA), a product generated during oxidative modification of
      low-density lipoprotein (LDL) and a major lipid extracted from human
      atherosclerotic plaques, has been shown to elicit smooth muscle cell (SMC)
      proliferation and inflammation, thereby being involved in atherogenesis.
      Recently, statins, an inhibitor of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA)
      reductase, have been reported to reduce the risk of cardiovascular events and
      slows the progression of atherosclerosis, at least partly, via pleiotropic
      effects. However, the effect of statin on the LPA-signaling in SMCs remains to be
      elucidated. In this study, we investigated whether and how pitavastatin could
      inhibit the LPA-induced proliferation and monocyte chemoattractant protein-1 (MCP
      1) expression in cultured human aortic SMCs. LPA dose-dependently increased
      intracellular reactive oxygen species (ROS) generation in SMCs, which was blocked
      by diphenylene iodonium (DPI), an inhibitor of NADPH oxidase or pitavastatin. The
      anti-oxidative property of pitavastatin was prevented by simultaneous treatment
      of geranylgeranyl pyrophosphate. Furthermore, overexpression of dominant negative
      Rac-1 mutant was found to inhibit the LPA-induced ROS generation in SMCs. LPA
      induced Rac-1 activation in SMCs, which was suppressed by pitavastatin or LPA
      receptor antagonist. Pitavastatin, DPI, and an anti-oxidant N-acetylcysteine
      inhibited the LPA-induced proliferation and MCP-1 gene expression in SMCs. These
      results suggest that pitavastatin could block the LPA-induced proliferation and
      MCP-1 expression in SMCs by suppressing Rac-1-mediated NADPH oxidase-dependent
      ROS generation. Our present study provides a novel beneficial aspect of
      pitavastatin; pitavastatin may act as a blocker of the LPA-signaling in SMCs.

PMID- 17178256
TI  - ATM-mediated response to DNA double strand breaks in human neurons derived from
      stem cells.
AB  - Ataxia-telangiectasia (A-T) is a multi-system genomic instability syndrome that
      is caused by loss or inactivation of the ATM protein kinase. ATM is largely
      nuclear in proliferating cells, and activates an extensive network of pathways in
      response to double strand breaks (DSBs) in the DNA by phosphorylating key
      proteins in these pathways. The prominent symptom of A-T is neuronal
      degeneration, making the elucidation of ATM's functions in neurons essential to
      understanding the disease. It has been suggested that ATM is cytoplasmic in
      neurons and functions in processes that are not associated with the DNA damage
      response. Recently we showed that in human neuron-like cells obtained by in vitro
      differentiation of neuroblastomas, ATM was largely nuclear and mediated the DSB
      response as in proliferating cells. We have now extended these studies to two
      additional model systems: neurons derived from human embryonic stem cells, and
      cortical neurons derived from neural stem cells. The results substantiate the
      notion that ATM is nuclear in human neurons and mediates the DSB response, the
      same as it does in proliferating cells. We present here unique and powerful model
      systems to further study the ATM-mediated network in neurons.

PMID- 17178257
TI  - On the association between statin and fracture: a Bayesian consideration.
AB  - BACKGROUND: The association between statin use and fracture risk is
      controversial, due to conflicting findings from previous studies. This study
      utilized the Bayesian approach to combine existing evidence and update the
      association with consideration of potential bias. METHODS: Data on the
      association between statin use and fracture incidence from 11 observational
      studies and 4 RCTs were synthesized by both empirical Bayesian analysis and fully
      Bayesian random-effects meta-analysis models. RESULTS: Empirical Bayesian
      analysis showed that statin use was associated with a reduction in hip fracture
      risk (OR=0.57, 95% credible interval (CrI): 0.46-0.71) and for non-vertebral
      (OR=0.69, 95% CrI, 0.63-0.74). These results were comparable with results from
      the fully Bayesian random-effects meta-analysis only for hip fracture (OR 0.56,
      95% CrI, 0.42-0.73), but not for non-vertebral fracture (OR 0.77, 95% CrI, 0.58
      1.03). The probability that statin use reduces fracture risk by at least 20% was
      0.995 for hip fracture and 0.61 for non-vertebral fracture. Under the assumption
      that bias over-estimates the true OR by 20%, there is still a probability of 0.97
      that statin use reduces hip fracture risk by at least 20%; however, the effect on
      non-vertebral fracture was much less robust with a probability of 0.27.
      CONCLUSIONS: Results of this Bayesian consideration are highly consistent with
      the hypothesis that statin use reduces hip fracture, but the association between
      statin use and non-vertebral fracture remains uncertain. The Bayesian approach
      presented here has the ability to help updating existing evidence as new data
      becomes available.

PMID- 17178258
TI  - BBA in the year 2007.

PMID- 17178259
TI  - Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance.
AB  - Lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl-coenzyme A inhibitors
      (statins), are widely used in the treatment and prevention of atherosclerotic
      disease. The benefits of statins are well documented. However, lipid-lowering
      drugs may cause myopathy, even rhabdomyolysis, the risk of which is increased by
      certain interactions. Simvastatin, lovastatin, and atorvastatin are metabolized
      by cytochrome P450 (CYP) 3A4 (simvastatin acid is also metabolized by CYP2C8);
      their plasma concentrations and risk of myotoxicity are greatly increased by
      strong inhibitors of CYP3A4 (eg, itraconazole and ritonavir). Weak or moderately
      potent CYP3A4 inhibitors (eg, verapamil and diltiazem) can be used cautiously
      with small doses of CYP3A4-dependent statins. Cerivastatin is metabolized by
      CYP2C8 and CYP3A4, and fluvastatin is metabolized by CYP2C9. The exposure to
      fluvastatin is increased by less than 2-fold by inhibitors of CYP2C9.
      Pravastatin, rosuvastatin, and pitavastatin are excreted mainly unchanged, and
      their plasma concentrations are not significantly increased by pure CYP3A4
      inhibitors. Cyclosporine (INN, ciclosporin) inhibits CYP3A4, P-glycoprotein
      (multidrug resistance protein 1), organic anion transporting polypeptide 1B1
      (OATP1B1), and some other hepatic uptake transporters. Gemfibrozil and its
      glucuronide inhibit CYP2C8 and OATP1B1. These effects of cyclosporine and
      gemfibrozil explain the increased plasma statin concentrations and, together with
      pharmacodynamic factors, the increased risk of myotoxicity when coadministered
      with statins. Inhibitors of OATP1B1 may decrease the benefit/risk ratio of
      statins by interfering with their entry into hepatocytes, the site of action.
      Lipid-lowering drugs can be involved also in other interactions, including those
      between enzyme inducers and CYP3A4 substrate statins, as well as those between
      gemfibrozil and CYP2C8 substrate antidiabetics. Knowledge of the pharmacokinetic
      and pharmacodynamic properties of lipid-lowering drugs and their interaction
      mechanisms helps to avoid adverse interactions, without compromising therapeutic
      benefits.

PMID- 17178260
TI  - Sulfadoxine-pyrimethamine pharmacokinetics in malaria: pediatric dosing
      implications.
AB  - OBJECTIVE: Our objective was to characterize the pharmacokinetic properties of
      sulfadoxine-pyrimethamine in African adults and children with acute falciparum
      malaria. Despite decades of widespread use, there are few data to inform dose
      recommendations. METHODS: In a prospective multicenter pharmacokinetic study in
      307 patients with acute falciparum malaria, capillary blood concentrations of
      sulfadoxine and pyrimethamine were determined at 9 visits over a period of 42
      days by mass spectrometry. RESULTS: After adjustment for dose, the area under the
      concentration-time curves (AUCs) of sulfadoxine and pyrimethamine in children
      aged 2 to 5 years were half of those in adults (median AUC, 410 microg/mL x d
      [interquartile range (IQR), 126-705 microg/mL x d] versus 816 microg/mL x d [IQR,
      536-1150 microg/mL x d] [P = .0001] for sulfadoxine and 620 ng/mL x d [IQR, 229
      1399 ng/mL x d] versus 1518 ng/mL x d [IQR, 1117-2013 ng/mL x d] for
      pyrimethamine). The effect of age on the AUC of sulfadoxine and pyrimethamine
      reflected higher clearance rates and larger apparent volumes of distribution in
      children aged 2 to 5 years when compared with adults (median clearance, 64.5 mL x
      kg(-1) x d(-1) [IQR, 46.2-132.6 mL x kg(-1) x d(-1)] versus 32.7 mL x kg(-1) x d(
      1) [IQR, 22.3-52.2 mL x kg(-1) x d(-1)] for sulfadoxine [P = .0001] and 1.77 L x
      kg(-1) x d(-1) [IQR, 1.0-3.0 L x kg(-1) x d(-1)] versus 0.85 L x kg(-1) x d(-1)
      [IQR, 0.62-1.21 L x kg(-1) x d(-1)] for pyrimethamine [P = .0001]; median volume
      of distribution, 413 mL/kg [IQR, 299-711 mL/kg] versus 372 mL/kg [IQR, 267-488
      mL/kg] for sulfadoxine [P = .0021] and 6.28 L/kg [IQR, 3.83-11.24 L/kg] versus
      3.83 L/kg [IQR, 2.73-5.11 L/kg] for pyrimethamine [P = .0001]). Day 7
      concentrations of both sulfadoxine and pyrimethamine provided good surrogate
      measures (R(2) >or= 0.72) of their respective AUCs. CONCLUSIONS: Pharmacokinetic
      factors may contribute to the increased risk of sulfadoxine-pyrimethamine
      antimalarial treatment failure in young children. The current dose
      recommendations need revision. We predict that children aged 2 to 5 years should
      be treated with 1 g sulfadoxine/50 mg pyrimethamine to achieve drug
      concentrations equivalent to those in adults.

PMID- 17178261
TI  - Differential effect of chronic renal failure on the pharmacokinetics of lidocaine
      in patients receiving and not receiving hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: The effect of chronic renal failure (CRF) on the
      pharmacokinetics of lidocaine, a drug cleared almost exclusively by hepatic
      metabolism, has thus far only been evaluated in patients undergoing regular
      hemodialysis. This study had 2 objectives: (1) to investigate the effect of CRF
      on the pharmacokinetics of lidocaine in both patients undergoing hemodialysis and
      patients not undergoing hemodialysis and (2) to test the effects of plasma from
      the patients examined and of lidocaine metabolites possibly accumulated in vivo
      on lidocaine biotransformation in vitro. METHODS: In a clinical investigation we
      studied the kinetics of lidocaine and its metabolites, monoethylglycinexylidide
      (MEGX) and glycinexylidide (GX), after intravenous injection of 1 mg/kg lidocaine
      in 15 healthy volunteers (creatinine clearance [CL(cr)] >80 mL/min x 1.73 m(-2)),
      10 subjects with moderate renal insufficiency (CL(cr) between 30 and 60 mL/min x
      1.73 m(-2)), 10 subjects with severe renal insufficiency (CL(cr) <30 mL/min x
      1.73 m(-2)), and 10 functionally anephric patients undergoing long-term
      hemodialysis. In experiments in vitro we determined the effects of plasma and GX
      on the formation rate of the primary lidocaine metabolite, MEGX, by use of human
      liver microsomes. RESULTS: In patients not undergoing hemodialysis, lidocaine
      kinetic parameters were altered in proportion to the degree of renal function
      impairment, but only in patients with severe renal insufficiency were differences
      statistically significant: clearance was about half that of control subjects
      (mean +/- SD, 6.01 +/- 2.54 mL/min x kg versus 11.87 +/- 2.97 mL/min x kg; P <
      .001), and half-life was approximately doubled (4.55 +/- 1.71 hours versus 2.24
      +/- 0.55 hours, P < .001). No such alterations were observed in patients
      undergoing regular hemodialysis, whose values were similar to those of the
      control group. The steady-state volume of distribution and MEGX levels were
      independent of renal function, whereas GX levels were more than double those of
      control subjects (P < .05) in all CRF groups. No inhibitory effect of plasma was
      observed, for any of the subjects examined, on lidocaine biotransformation in
      vitro. GX was found to be a competitive inhibitor, but its apparent inhibition
      constant value (52 +/- 6 micromol/L) was 2 orders of magnitude higher than its
      concentrations in vivo. CONCLUSIONS: Our in vivo findings have both clinical and
      methodologic implications: (1) Lidocaine dose adjustment may be required in
      patients with severe renal insufficiency who are not receiving hemodialysis. (2)
      Results of studies evaluating the effect of CRF on metabolic drug disposition are
      not of general validity, unless both patients undergoing hemodialysis and
      patients not undergoing hemodialysis have been examined. Our in vitro
      observations exclude that impairment of lidocaine disposition is the result of
      direct inhibition of metabolizing enzymes by accumulated metabolites or uremic
      toxins. Alternative mechanisms, suggested by the results of recent in vitro
      studies, are discussed.

PMID- 17178262
TI  - Organic anion transporting polypeptide 2B1 is a high-affinity transporter for
      atorvastatin and is expressed in the human heart.
AB  - BACKGROUND: The cardiac effects of statins are subject to controversial
      discussion, and the mechanism of their uptake into the human heart is unknown. A
      candidate protein is the organic anion transporting polypeptide (OATP) 2B1
      (SLCO2B1), because related transporters are involved in the uptake of statins
      into the human liver. In this study we examine OATP2B1 expression in the human
      heart and describe statins as inhibitors and substrates of OATP2B1. METHODS: The
      expression of OATP2B1 was analyzed in 46 human atrial and 15 ventricular samples,
      including samples from hearts with dilated cardiomyopathy and hearts with
      ischemic cardiomyopathy. RESULTS: Significant messenger ribonucleic acid
      expression was found in all samples, with no difference in the diseased hearts.
      However, patients who had taken atorvastatin exhibit decreased OATP2B1 messenger
      ribonucleic acid expression compared with patients with no statin treatment.
      OATP2B1 protein was detected at approximately 85 kd in atrial samples, as well as
      ventricular samples, and could be localized to the vascular endothelium.
      Furthermore, estrone-3-sulfate transport into OATP2B1-overexpressing Madin-Darby
      canine kidney II cells was inhibited by various drugs, including atorvastatin,
      simvastatin, cerivastatin, glyburide (INN, glibenclamide), and gemfibrozil, with
      the most pronounced effect being found for atorvastatin (inhibition constant, 0.7
      +/- 0.4 micromol/L). Whereas simvastatin (lactone) itself was not transported by
      OATP2B1, atorvastatin was identified as a high-affinity substrate for OATP2B1
      (Michaelis-Menten constant, 0.2 micromol/L) by direct transport measurement via
      liquid chromatography-tandem mass spectrometry. CONCLUSION: OATP2B1 is a high
      affinity uptake transporter for atorvastatin and is expressed in the vascular
      endothelium of the human heart, suggesting its involvement in cardiac uptake of
      atorvastatin.

PMID- 17178263
TI  - The cyclooxygenase 2 genetic variant -765G>C does not modulate the effects of
      celecoxib on prostaglandin E2 production.
AB  - OBJECTIVE: Our objective was to assess the role of the reportedly functional
      PTGS2 (prostaglandin-endoperoxide synthase 2/cyclooxygenase [COX] 2) promoter
      mutation -765G>C for the COX-2-inhibiting effects of celecoxib. METHODS: Twenty
      healthy carriers of the -765GG genotype and -765CC genotype (n = 10 each)
      received 200 mg of celecoxib orally. Blood samples were drawn at baseline and at
      1, 3, 6, 9, and 24 hours after administration. Plasma concentrations of celecoxib
      and concentrations of prostaglandin E(2) (PGE(2)) produced by peripheral blood
      monocytes stimulated ex vivo with bacterial lipopolysaccharide (LPS) were
      analyzed by liquid chromatography-tandem mass spectrometry. Expression of COX-2
      messenger ribonucleic acid and protein expression with and without LPS
      stimulation were analyzed by real-time polymerase chain reaction and Western
      blotting, respectively. RESULTS: LPS induced PGE(2) production (P < .001), and
      celecoxib reduced PGE(2) production from 19.3 +/- 7.2 ng/mL at baseline to 7.4 +/
      4.8 ng/mL at 1 hour (P < .001). The effect of celecoxib lasted for 9 hours
      (repeated-measures ANOVA, P <or= .001). Celecoxib inhibited PGE(2) production at
      a potency (ie, 50% effective concentration [EC(50)]) of 155.1 ng/mL (95%
      confidence interval, 101.6-208.5 ng/mL) in the homozygous carriers of the PTGS2
      wild-type -765G allele and at a potency (EC(50)) of 186.6 ng/mL (95% confidence
      interval, 142.6-230.5 ng/mL) in the homozygous carriers of the PTGS2 variant 
      765C allele, which was not statistically significantly different (P = .36).
      Baseline PGE(2) concentrations, minimum baseline PGE(2) concentrations, and areas
      under the PGE(2) concentration versus time curve also did not differ between
      PTGS2 genotypes (P > .28). LPS up-regulated COX-2 messenger ribonucleic acid
      expression (P = .016) but was independent of genotype (P = .36). COX-2 protein
      expression was similar for both -765G>C genotypes (P = .63). CONCLUSION: The
      PTGS2 -765G>C single-nucleotide polymorphism does not modulate COX-2 inhibitory
      effects of celecoxib as assessed by an ex vivo whole blood assay. Thus the
      results indicate the need for further investigation toward PTGS2 pharmacogenetics
      based prescription of celecoxib.

PMID- 17178264
TI  - Beta2-adrenergic receptor polymorphisms and treatment-induced regression of left
      ventricular hypertrophy in hypertension.
AB  - OBJECTIVES: Although blood pressure is considered the major determinant of left
      ventricular hypertrophy in hypertension, genetic variability is increasingly
      being considered among the factors influencing this complication. beta(2)
      Adrenergic receptors (beta(2)ARs) are up-regulated in hypertension and largely
      polymorphic within the human population. Recently, we have shown that the Glu27
      beta(2)AR variant is strongly associated with cardiac hypertrophy in
      hypertension. The objective of this study is to verify whether this polymorphism
      also affects hypertrophy regression in response to antihypertensive therapy.
      METHODS: In a prospective follow-up study we screened 970 hypertensive patients
      of Caucasian descent for the Gly16Arg, Gln27Glu, and Thr164Ile beta(2)AR
      polymorphisms and left ventricular echocardiographic hypertrophy and assigned
      selected patients to enalapril or atenolol to assess left ventricular hypertrophy
      regression after 2-year follow-up. Results were stratified according to treatment
      and the Glu27Gln polymorphism of the beta(2)AR. In cells with stable
      overexpression of the Glu27 or Gln27 variant of beta(2)AR, we also explored the
      implications of this polymorphism on hypertrophy-related intracellular signal
      transduction. RESULTS: Among hypertensive patients, the Gly16 allele was found in
      63% of patients and the Glu27 allele was found in 40.6%. Both polymorphisms were
      in linkage disequilibrium, as expected. Four hundred forty-one hypertrophic
      hypertensive patients completed the 2-year follow-up. At baseline, patients
      carrying at least 1 allele of the Glu27 variant presented with a larger cardiac
      size despite similar blood pressure levels (142.9 +/- 22.5 g/m(2) in Glu27
      carriers versus 138.2 +/- 18.4 g/m(2) in Gln27 carriers, P < .02). Blood pressure
      normalization was achieved by both drugs. At follow-up, compared with the Gln27
      patients, the Glu27 patients showed a larger reduction in hypertrophy when
      treated with enalapril (percent change in left ventricular mass, -6.3% +/- 7.7%
      in Glu27 carriers versus -2.18% +/- 7.9% in Gln27 carriers; P < .05) but not with
      atenolol therapy (-2.8% +/- 8.9% in Glu27 carriers versus -2.4% +/- 8.8% in Gln27
      carriers, P = not significant). In in vitro studies the activation of p38 and
      extracellular signal-regulated kinase (ERK-) 1/2 (data not shown) and the
      activity of the atrial natriuretic factor (ANF) promoter after isoproterenol
      (INN, isoprenaline) stimulation were larger in Glu27 beta(2)AR overexpressing
      cells than in Gln27 beta(2)AR overexpressing cells (fold difference compared with
      unstimulated cells, 9.7 +/- 2.9 for Glu27 beta(2)AR versus 4.2 +/- 0.3 for Gln27
      beta(2)AR; P < .05). CONCLUSIONS: The Glu27 variant of beta(2)AR enhances
      hypertension-induced left ventricular hypertrophy. In these patients angiotensin
      converting enzyme inhibitors are more efficient than beta-blockers in reducing
      cardiac size.

PMID- 17178265
TI  - Effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of
      amlodipine in healthy Korean subjects.
AB  - BACKGROUND AND OBJECTIVE: 1,4-Dihydropyridine calcium channel blockers, including
      amlodipine, are mainly metabolized by cytochrome P450 (CYP) 3A. We investigated
      the effect of CYP3A5*3 genotype on the pharmacokinetics and pharmacodynamics of
      amlodipine in healthy Korean male subjects. METHODS: Forty healthy male
      participants were enrolled and genotyped for the CYP3A5*3 gene. Each subject
      ingested a 5-mg dose of amlodipine, and plasma amlodipine concentrations were
      measured for 144 hours after dosing. Blood pressure and pulse rate were also
      measured for pharmacodynamic analysis. RESULTS: Among the 40 volunteers, 24 were
      CYP3A5*3/*3 carriers and 16 were CYP3A5*1 carriers (CYP3A5*1/*1 in 2 and
      CYP3A5*1/*3 in 14). The difference in the oral clearance of amlodipine approached
      statistical significance between the 2 major genotype groups, with CYP3A5*1
      carriers (27.0 +/- 8.2 L/h) showing 20% lower clearance than CYP3A5*3/*3 carriers
      (32.4 +/- 10.2 L/h) (P = .063). However, the mean area under the plasma
      concentration-time curve of amlodipine was 200.9 +/- 61.9 ng . h/mL for CYP3A5*1
      carriers and 167.6 +/- 45.0 ng . h/mL for CYP3A5*3/*3 carriers (P = .029).
      Moreover, the peak plasma concentration was significantly higher in CYP3A5*1
      carriers (3.8 +/- 1.1 ng/mL) than in CYP3A5*3/*3 carriers (3.1 +/- 0.8 ng/mL) (P
      = .037). Pharmacodynamically, blood pressure and pulse rate were not
      significantly different between the 2 groups. CONCLUSIONS: CYP3A5*3/*3 carriers
      exhibited lower plasma amlodipine concentrations than CYP3A5*1 carriers. These
      findings suggest that the polymorphic CYP3A5 gene affects the disposition of
      amlodipine and provides a plausible explanation for interindividual variability
      in amlodipine disposition.

PMID- 17178266
TI  - Pharmacokinetics and pharmacodynamics of rosiglitazone in relation to CYP2C8
      genotype.
AB  - OBJECTIVES: Rosiglitazone is metabolically inactivated predominantly via the
      cytochrome P450 (CYP) enzyme CYP2C8. The functional impact of the CYP2C8*3 allele
      coding for the Arg139Lys and Lys399Arg amino acid substitutions is controversial.
      The purpose of this was to clarify the role of this polymorphism with regard to
      the pharmacokinetics and clinical effects of rosiglitazone. METHODS: From a large
      sample of healthy volunteers, 14 carriers of the CYP2C8*1/*1 allele, 13 carriers
      of the *1/*3 allele, and 4 carriers the *3/*3 allele were selected for a clinical
      study. Rosiglitazone (8 mg) single-dose and multiple-dose pharmacokinetics and
      its effects on glucose level and body weight were monitored. Plasma and urine
      concentrations of rosiglitazone and desmethylrosiglitazone were measured, and
      kinetics was analyzed by noncompartmental and population-kinetic compartmental
      methods. RESULTS: Mean total clearance values were 0.033 L x h(-1) x kg(-1) (95%
      confidence interval [CI], 0.030-0.037 L x h(-1) x kg(-1)), 0.038 L x h(-1) x kg(
      1) (95% CI, 0.033-0.044 L x h(-1) x kg(-1)), and 0.046 L x h(-1) x kg(-1) (95%
      CI, 0.033-0.058 L x h(-1) x kg(-1)) in carriers of CYP2C8 genotypes *1/*1, *1/*3,
      and *3/*3, respectively, on day 1 (P = .02, ANOVA [F test]). Rosiglitazone
      kinetics could be adequately described by a 1-compartmental model with first
      order absorption. Besides CYP2C8 genotype, body weight was a significant
      covariate (P < .001, log-likelihood ratio test). Elimination half-lives were 4.3,
      3.5, and 2.9 hours in CYP2C8*1/*1, *1/*3, and *3/*3 carriers, respectively.
      Clearance of desmethylrosiglitazone was also higher in CYP2C8*3 allele carriers,
      with mean values of 1.96 L/h (95% CI, 1.42-2.69 L/h), 2.22 L/h (95% CI, 1.61-3.04
      L/h), and 2.47 L/h (95% CI, 1.80-3.39 L/h), respectively (P = .03). The plasma
      glucose area under the concentration curve was significantly lower after 14 days
      of taking rosiglitazone compared with day 1 (P = .01, paired t test), but no
      relationship of the glucose-lowering effect of rosiglitazone with CYP2C8 genotype
      was observed. CONCLUSIONS: This study showed that the CYP2C8*3 allele confers
      higher in vivo metabolic capacity than the wild-type CYP2C8*1 allele but the
      pharmacokinetic differences resulting from CYP2C8*3 were quantitatively moderate.

PMID- 17178268
TI  - ABCB1 genetic variability and methadone dosage requirements in opioid-dependent
      individuals.
AB  - BACKGROUND AND OBJECTIVES: The most common treatment for opioid dependence is
      substitution therapy with another opioid such as methadone. The methadone dosage
      is individualized but highly variable, and program retention rates are low due in
      part to nonoptimal dosing resulting in withdrawal symptoms and further heroin
      craving and use. Methadone is a substrate for the P-glycoprotein transporter,
      encoded by the ABCB1 gene, which regulates central nervous system exposure. This
      retrospective study aimed to investigate the influence of ABCB1 genetic
      variability on methadone dose requirements. METHODS: Genomic deoxyribonucleic
      acid was isolated from opioid-dependent subjects (n = 60) and non-opioid
      dependent control subjects (n = 60), and polymerase chain reaction-restriction
      fragment length polymorphism and allele-specific polymerase chain reaction were
      used to determine the presence of single nucleotide polymorphisms at positions
      61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE
      software (version 2.1). RESULTS: There were no significant differences in the
      allele or genotype frequencies of the individual single nucleotide polymorphisms
      or haplotypes between the 2 populations. ABCB1 genetic variability influenced
      daily methadone dose requirements, such that subjects carrying 2 copies of the
      wild-type haplotype required higher doses compared with those with 1 copy and
      those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d,
      respectively; P = .029). In addition, carriers of the AGCTT haplotype required
      significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d,
      respectively; P = .04). CONCLUSION: Although ABCB1 genetic variability is not
      related to the development of opioid dependence, identification of variant
      haplotypes may, after larger prospective studies have been performed, provide
      clinicians with a tool for methadone dosage individualization.

PMID- 17178267
TI  - ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma
      levels and response to treatment.
AB  - BACKGROUND AND OBJECTIVE: The in vivo implication of various cytochrome P450
      (CYP) isoforms and of P-glycoprotein on methadone kinetics is unclear. We aimed
      to thoroughly examine the genetic factors influencing methadone kinetics and
      response to treatment. METHODS: Genotyping for CYP1A2, CYP2B6, CYP2C9, CYP2C19,
      CYP2D6, CYP3A4, CYP3A5, ABCB1, and UGT2B7 polymorphisms was performed in 245
      patients undergoing methadone maintenance treatment. To assess CYP3A activity,
      the patients were phenotyped with midazolam. RESULTS: The patients with lower
      CYP3A activity presented higher steady-state trough (R,S)-methadone plasma levels
      (4.3, 3.0, and 2.3 ng/mL x mg for low, medium, and high activity, respectively; P
      = .0002). As previously reported, CYP2B6*6/*6 carriers had significantly higher
      trough (S)-methadone plasma levels (P = .0001) and a trend toward higher (R)
      methadone plasma levels (P = .07). CYP2D6 ultrarapid metabolizers presented lower
      trough (R,S)-methadone plasma levels compared with the extensive or intermediate
      metabolizers (2.4 and 3.3 ng/mL x mg, respectively; P = .04), whereas CYP2D6 poor
      metabolizer status showed no influence. ABCB1 3435TT carriers presented lower
      trough (R,S)-methadone plasma levels (2.7 and 3.4 ng/mL . mg for 3435TT and
      3435CC carriers, respectively; P = .01). The CYP1A2, CYP2C9, CYP2C19, CYP3A5, and
      UGT2B7 genotypes did not influence methadone plasma levels. Only CYP2B6 displayed
      a stereoselectivity in its activity. CONCLUSION: In vivo, CYP3A4 and CYP2B6 are
      the major CYP isoforms involved in methadone metabolism, with CYP2D6 contributing
      to a minor extent. ABCB1 genetic polymorphisms also contribute slightly to the
      interindividual variability of methadone kinetics. The genetic polymorphisms of
      these 4 proteins had no influence on the response to treatment and only a small
      influence on the dose requirement of methadone.

PMID- 17178269
TI  - Direct and rapid inhibition of factor Xa by otamixaban: a pharmacokinetic and
      pharmacodynamic investigation in patients with coronary artery disease.
AB  - BACKGROUND: New anticoagulants that combine effective anticoagulation with low
      bleeding rates are still sought after. We investigated the safety,
      pharmacokinetics, and pharmacodynamics of otamixaban, a direct factor Xa
      inhibitor, in patients with stable coronary artery disease. METHODS: This was a
      randomized, placebo-controlled, double-blind, multicenter study in 119 patients
      with stable coronary artery disease taking maintenance doses of their
      comedication. Of these patients, 50% had mild renal impairment (creatinine
      clearance >45 mL/min but <80 mL/min). Patients were randomized in a 4:1 ratio to
      receive either otamixaban or placebo as a 1-minute bolus followed by a 24-hour
      continuous infusion. Anti-factor Xa activity, clotting times (activated partial
      thromboplastin time, dilute prothrombin time, Russell's viper venom test), and
      international normalized ratio were measured. RESULTS: All patients completed the
      study according to the protocol. No major or minor bleeding occurred according to
      Thrombosis in Myocardial Infarction criteria. Anti-factor Xa activity and
      anticoagulant effect were measurable early after the start of the infusion and
      remained during the infusion. Upon cessation, these effects declined rapidly and
      returned to baseline within 6 hours after the end of infusion. Anti-factor Xa
      activity coincided with the otamixaban plasma concentrations. The fold changes
      from baseline at the end of infusion with regard to the clotting times ranged
      from 1.7 to 4.4 (1.15 for placebo), 1.29 to 3.15 (0.98 for placebo), and 1.19 to
      2.11 (0.94 for placebo) for Russell's viper venom test, dilute prothrombin time,
      and activated partial thromboplastin time, respectively, and ranged from 0.94 to
      1.70 (0.94 for placebo) for the international normalized ratio. CONCLUSION: In
      patients with stable coronary artery disease taking maintenance doses of their
      usual concomitant medication, otamixaban exerts a rapid onset of anticoagulation
      and anti-factor Xa activity. Our data provide evidence that further studies are
      warranted to investigate the safety and efficacy of otamixaban in the target
      population.

PMID- 17178270
TI  - Nicotine intake and dose response when smoking reduced-nicotine content
      cigarettes.
AB  - OBJECTIVES: The progressive reduction of the nicotine content of cigarettes has
      been suggested as a way to wean smokers from nicotine and tobacco. As a first
      step in evaluating this strategy, we studied smokers smoking cigarettes
      containing tobacco with differing nicotine content. METHODS: Twelve healthy
      smokers participated in a semiblinded, within-subject, crossover study. Subjects
      were asked to smoke 1 of their usual brand of cigarette and then on 5 subsequent
      occasions to smoke a research cigarette, each with differing nicotine content.
      The research cigarettes contained 0.6 to 10.1 mg nicotine per cigarette. Plasma
      nicotine and blood carboxyhemoglobin levels, as well as subjective and
      cardiovascular responses, were measured after smoking. Systemic nicotine intake
      per cigarette was estimated by use of plasma nicotine concentrations over time
      and clearance data from the general population. RESULTS: Systemic nicotine intake
      (0.26-1.47 mg per cigarette) varied with nicotine content of the cigarette (r =
      0.82, P < .001). Compensation when smoking single low-nicotine content cigarettes
      ranged from -1% (95% confidence interval, -23% to 21%) to 34% (95% confidence
      interval, -39% to 107%) for 1-mg to 8-mg research cigarettes. Carbon monoxide
      intake and estimated tar exposure were similar across cigarettes. Low-nicotine
      content cigarettes were rated as being of lower quality and less satisfying than
      the 12-mg research cigarette or the usual brand (P < .05 for both comparisons).
      Cigarette smoking increased heart rate and decreased skin temperature, but the
      nicotine dose-response curve flattened at higher doses, with a maximal response
      being observed in cigarettes at a nicotine content level of about 8 mg.
      CONCLUSIONS: Our study suggests that reduced-nicotine content cigarettes are
      reasonable candidates for trying to reduce the level of nicotine addiction in
      smokers. The flat nicotine dose-cardiovascular response curve is consistent with
      other studies demonstrating tolerance to the cardiovascular effects of nicotine.

PMID- 17178271
TI  - Comment on severe arrhythmia as a result of the interaction of cetirizine and
      pilsicainide in a patient with renal insufficiency.

PMID- 17178273
TI  - Drug interaction of tizanidine and ciprofloxacin: case report.

PMID- 17178274
TI  - CYP3A5 polymorphism and alprazolam pharmacokinetics/pharmacodynamics.

PMID- 17178277
TI  - Biomarkers of response to preoperative chemoradiation in esophageal cancers.
AB  - To identify a panel of biomarkers that predicts response of esophageal cancers to
      preoperative chemoradiation, our group profiled the gene expression of
      pretreatment cancer biopsies from patients with esophageal cancer. Six (32%) of
      these patients had pathologic complete response. All cancers except one that
      achieved pathologic complete response (83%) clustered in one molecular type (type
      I), while cancers that achieved less than pathologic complete response with one
      exception clustered in another molecular type (type II). Activated NF-kappaB was
      significantly associated with aggressive pathology. These data indicate that
      expression analysis of a limited set of biomarkers selected from the list of
      genes that were differentially regulated between the two subtypes can increase
      predictive power, and suggest that esophageal cancer with activated NF-kappaB may
      result in poor treatment outcome.

PMID- 17178278
TI  - What is the future of oncology? National Cancer Institute initiatives to improve
      research, development, and implementation in cancer prevention and treatment.
AB  - To improve the efficiency and effectiveness with which we bring novel cancer
      treatment and prevention strategies into routine clinical use, the National
      Cancer Institute has commissioned the Clinical Trials Working Group to
      restructure its activities related to clinical trials. A total of 22 initiatives
      have been developed and are being implemented under the rubrics of Coordination,
      Prioritization/Scientific Quality, Standardization, Operational Efficiency, and
      Integrated Management. A similar model was recently applied to the newly formed
      Translational Research Working Group, which will focus on more efficient
      translation of scientific discoveries arising from the laboratory, clinic, or
      population into early phase clinical testing.

PMID- 17178279
TI  - Adjuvant therapy for pancreatic cancer: current status, future directions.
AB  - Progress in the management of adenocarcinoma of the pancreas has clearly been
      documented in recent years. Surgical outcomes have improved dramatically, and the
      preponderance of data from randomized clinical trials affirm that adjuvant
      therapy, in the form of combination chemoradiotherapy, improves outcomes over
      surgery alone in patients with resected disease. Newer chemotherapeutic agents
      such as gemcitabine have led to significant improvements over 5-fluorouracil
      alone, and patients have benefited from improved methods of delivering conformal
      radiotherapy. As the clinical benefits of postoperative adjuvant therapy become
      increasingly evident, researchers have begun to explore the utility of including
      preoperative or "neoadjuvant" regimens to standard 5-fluorouracil-based
      chemoradiotherapy. Initial results with this strategy are promising, and will
      likely influence the direction of future research. A growing understanding of the
      molecular biology of the disease has opened doors to rich new areas of research,
      and targeted therapies will likely play an important role in newly developing
      treatment paradigms. Just cause for optimism exists, but much work remains to be
      done. New adjuvant therapies need to be developed and tested, in carefully
      designed, well-executed, efficient clinical trials.

PMID- 17178280
TI  - Molecular biology of colorectal cancer: new targets.
AB  - Colorectal cancer is an ideal model in which to study malignant progression from
      the molecular-genetic perspective because different stages of the same malignancy
      coexist within each patient. Approximately 75% of colorectal cancer cases are
      sporadic and the remaining are familial disease, yet genetic mutations that have
      been identified account for only 5% to 6% of inherited cases. The two major
      pathways by which mutational changes leading to colorectal cancer occur are
      chromosomal instability and microsatellite instability. This article discusses
      genes and signaling pathways involved in development of inherited disease, as
      well as the association of some of these pathways with sporadic cases.
      Furthermore, therapies targeting active pathways in colorectal carcinogenesis,
      including the vascular endothelial growth factor and epidermal growth factor
      receptor tyrosine kinase, have shown promising results in clinical trials are now
      included in standard recommended treatment.

PMID- 17178281
TI  - Successful gastrointestinal cancer drug development.
AB  - A large number of new drugs have been approved over the past 10 years for the
      treatment of both common and rare gastrointestinal malignancies. Many other
      agents, however, have failed at a great cost of financial and patient resources.
      Drug development must identify potentially active compounds and reveal the most
      effective and least toxic manner and population in which to administer compounds.
      Pharmaceutical companies must show therapeutic efficacy and achieve regulatory
      approval as well as success in the marketplace to recoup their investment. It is
      worth examining successful examples of drug development such as imatinib, delayed
      but eventually successful agents such as oxaliplatin, as well as failures such as
      SU-5416, and applying those lessons to current and future drug development.

PMID- 17178282
TI  - Planned treatment interruptions and chemotherapy-free intervals in the treatment
      of metastatic colorectal cancer: time to start stopping?
AB  - Studies have begun to examine stop-and-go or intermittent chemotherapy strategies
      in patients with advanced colorectal cancer. Such strategies potentially may
      reduce cumulative toxicities associated with long-term therapies. In addition,
      planned interruptions in treatment would be expected to lower overall costs of
      treatment, and would clearly offer patients the opportunity to have breaks from
      oncology visits and associated toxicities of therapy. Greater efforts to define
      such strategies are necessary, particularly because patients with advanced
      colorectal cancer now have multiple lines of therapy planned and spend greater
      amounts of time on treatment. Several studies have suggested that interrupting
      oxaliplatin or irinotecan treatment may be acceptable in terms of efficacy and
      beneficial in terms of toxicity. This article will address these and other
      trials, as well as data relating to incorporation of biologic therapies into
      combination chemotherapy for patients with advanced colorectal cancer.

PMID- 17178283
TI  - Optimum use of biologics and role of maintenance therapy in colon cancer.
AB  - The current standard of care for the treatment of metastatic colorectal cancer
      involves at least six different regimens, and with the advent of new therapies,
      including biologic therapies, patients are projected to live beyond an average of
      2 years. Data suggest a synergy between the biologics, which are in their infancy
      in terms of utilization, and they are being tested in the adjuvant setting in
      stage II and stage III disease. Ongoing and future trials will determine how best
      to incorporate these medicines into combination chemotherapy and determine if
      these medicines (or others) will have a role in maintenance chemotherapy for
      patients with metastatic colon cancer. However, the concept of incorporating
      maintenance therapy for colon cancer is clearly not established. Maintenance
      therapy has a requirement for less toxicity than current front-line therapies,
      and over the coming years, new agents will become available that maintain
      response and improve quality of life. Clinical trials involving novel agents as
      maintenance therapy are needed.

PMID- 17178284
TI  - Is there a third-line therapy for metastatic colorectal cancer?
AB  - Selection of third-line treatment in metastatic colorectal cancer depends on the
      agents that have been used in prior therapy. A principle in treatment is to use
      all five of the active drugs in this setting (5-fluorouracil [5-FU], oxaliplatin,
      irinotecan, cetuximab, and bevacizumab) during the patient's overall treatment
      course for metastatic disease because cumulative use of available active drugs
      appears to increase overall survival. Currently, 5-FU/leucovorin (5
      FU/LV)/oxaliplatin (FOLFOX) or 5-FU/LV plus irinotecan (FOLFIRI) can be
      considered standard therapy in first-line treatment, with cross-over irinotecan
      or oxaliplatin-containing regimens as a component of several possible second-line
      regimens. On this scenario, third-line treatment can include the combination of
      irinotecan with cetuximab or bevacizumab or both or the use of cetuximab and
      bevacizumab in combination. Data from randomized trials on third-line treatment
      are needed.

PMID- 17178285
TI  - New techniques of liver surgery.
AB  - Techniques of liver resection for colorectal cancer metastases continue to
      evolve, and the range of patients who benefit from such treatment expands. With
      improvements in preoperative and intraoperative imaging, surgical strategies for
      reducing blood loss and maximizing excision of disease and residual liver
      function, patient selection, and chemotherapy, many of the traditional
      contraindications to hepatic resection are no longer absolute contraindications.
      Appreciable long-term survival after resection is observed in many patients for
      which resection would not have been considered an option until recently. Novel
      treatment strategies have been successful in converting nonresectable disease to
      resectable disease, with good survival outcome. Continued study of and experience
      with novel surgical techniques and treatment strategies will continue to improve
      outcomes in liver resection for metastatic colorectal cancer.

PMID- 17178286
TI  - Targeted agents for adjuvant therapy of colon cancer.
AB  - Adjuvant therapy for colorectal cancer consists primarily of combinations of 5
      fluorouracil/leucovorin (5-FU/LV) (with infusional or bolus 5-FU) with
      oxaliplatin or oral capecitabine. The angiogenesis inhibitor bevacizumab and the
      epidermal growth factor receptor inhibitor cetuximab have shown activity when
      combined with 5-FU/LV-based regimens as first-line treatment of advanced disease
      and are currently being evaluated as part of adjuvant therapy in colon cancer.
      Bevacizumab is being evaluated in combination with FOLFOX4 (5-FU/LV/oxaliplatin),
      FOLFOX6, or XELOX (capecitabine/oxaliplatin) in the National Surgical Adjuvant
      Breast and Bowel Project C08 trial, the AVANT (AVastin adjuvANT) trial, and the
      Intergroup Rectal Adjuvant trial. Cetuximab is being evaluated in combination
      with FOLFOX4 and FOLFOX6 in the North Central Cancer Treatment Group (NCCTG)
      N0147 trial and the Pan European Trials in Adjuvant Colon Cancer (PETTAC) 8
      trial.

PMID- 17178287
TI  - Variation in the human genome and the inherited basis of common disease.
AB  - The availability of a reference human genome sequence-an increasingly dense
      catalog-knowledge of common genetic variation, and new developments in technology
      present an unprecedented opportunity to systematically explore the genetic basis
      of complex human diseases such as cancer. An understanding of the common
      mutations that can cause distinct human cancers will be critical for identifying
      new targets for drug discovery, patient stratification for clinical trials, and
      analysis of drug response data to delineate classes of patients that respond to
      therapy. The genome structure of cancer can be investigated in several ways.
      Germline mutations can be investigated in large-scale, case-control, or family
      studies. Somatic alternations can be identified using state-of-the-art genomic
      technologies such as high-density oligonucleotide arrays and targeted
      resequencing. Combined, these approaches will lead to a better understanding of
      the cancer genome.

PMID- 17178289
TI  - Models of esophageal carcinogenesis.
AB  - Attempting to formulate a model for the development of esophageal cancer, we have
      undertaken three interrelated projects: (1) identification and characterization
      of stem cells as a basis to understand lineage specification in the normal
      esophageal squamous epithelium and possibly transdifferentiation into an
      intestinal metaplastic phenotype that defines Barrett's esophagus; (2)
      elucidation of the role of epidermal growth factor receptor and signaling
      mechanisms in proliferation and transformation in squamous cell carcinoma; and
      (3) modeling transformation in organotypic culture, a 3-dimensional culture
      system, as a platform for investigating epithelial-stromal interactions. It is
      hoped that development of these models for carcinogenesis will permit formulation
      of effective chemoprevention, diagnostic, and therapeutic strategies.

PMID- 17178291
TI  - Should preoperative or postoperative therapy be administered in the management of
      rectal cancer?
AB  - Combined-modality therapy consisting of surgery, radiation, and chemotherapy with
      5-fluorouracil is the recommended management for patients with stage II and III
      rectal cancer. The place of radiation therapy as part of this combined modality
      treatment for localized rectal cancer will be reviewed, and some of the novel
      chemoradiation combinations under investigation will be highlighted. Currently,
      there are two sequencing approaches for the adjuvant administration of pelvic
      radiation therapy. The first is surgical resection and, if the tumor is stage T(3
      4) and/or N(1-2), adjuvant postoperative chemoradiation and further chemotherapy.
      The second approach for patients with ultrasound T(3-4) or clinical T(4) disease
      is preoperative therapy followed by surgical resection and postoperative
      chemotherapy. The adjuvant radiation management approach in the United States and
      Europe has been shifting toward preoperative therapy to promote sphincter
      preserving surgery and decrease acute and late bowel toxicity. The recently
      published 5-year results of the randomized German CAO/ARO/AIO 94 trial of
      preoperative versus postoperative chemoradiation support a standard preoperative
      treatment approach. Preoperative chemoradiation therapy also allows for the
      investigation of innovative agents (capecitabine, oxaliplatin, irinotecan,
      bevacizumab, and cetuximab) in combination with pelvic radiation. These new
      combinations may have the potential to further increase the therapeutic benefit
      of neoadjuvant therapy.

PMID- 17178290
TI  - Functional imaging for early prediction of response to chemoradiotherapy: 3'
      deoxy-3'-18F-fluorothymidine positron emission tomography--a clinical application
      model of esophageal cancer.
AB  - Pathologic complete response after neoadjuvant chemoradiation therapy is
      associated with increased survival in esophageal cancer. Early detection of
      response or nonresponse to neoadjuvant chemoradiation might allow
      individualization of treatment strategies and avoidance of unnecessary treatment.
      Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) permits
      detection of changes in tumor proliferation before any change in tumor size
      occurs, and FDG-PET findings have been correlated with outcomes in esophageal
      cancer. However, FDG-PET may fail to distinguish between residual tumor and
      inflammation and between complete response and partial response with substantial
      residual tumor burden. PET with the nucleoside analogue 3'-deoxy-3'-18F
      fluorothymidine (FLT) has been found to be more accurate than FDG-PET in
      visualizing early changes in tumor proliferation. In a recent study in
      experimental models of esophageal cancer, FLT-PET was more accurate than FDG-PET
      in detecting early changes in proliferation following docetaxel and radiation
      therapy in human SEG-1 cells and mouse SEG-1 xenografts, including having a much
      stronger correlation with histologic findings. Clinical studies are needed to
      determine if FLT-PET can distinguish among degrees of response to neoadjuvant
      chemoradiation in patients with esophageal cancer.

PMID- 17178288
TI  - The angiogenic switch molecule, secreted FGF-binding protein, an indicator of
      early stages of pancreatic and colorectal adenocarcinoma.
AB  - Tumor angiogenesis has been related to the initiation as well as progression
      toward more aggressive behavior of human tumors. We will discuss genetic events
      underlying the initiation and progression of colorectal and pancreatic
      adenocarcinoma with a particular focus on the modulation of angiogenesis. A
      secreted fibroblast growth factor (FGF) binding protein (FGF-BP), which is an
      extracellular chaperone molecule for FGFs, has been shown to enhance FGF-mediated
      biochemical and biologic events and to be a crucial rate-limiting factor for
      tumor-dependent angiogenesis. Histochemical and in situ hybridization studies
      with archival samples show that FGF-BP is induced early during the initiation of
      colorectal and pancreatic adenocarcinoma. We will discuss the potential of this
      secreted protein as a serum marker to identify at-risk subjects.

PMID- 17178292
TI  - Can pelvic radiotherapy be omitted in select patients with rectal cancer?
AB  - Randomized prospective trials have shown the benefits of adjuvant radiotherapy in
      decreasing local recurrence rates in stage II and stage III rectal cancer.
      However, some patients with stage II lesions have relatively low risks of local
      recurrence when treated with modern surgery alone. This article will discuss
      important prognostic, diagnostic, and therapeutic factors including depth of
      tumor invasion, tumor location, improvements in staging with endorectal
      ultrasound and magnetic resonance imaging, enhanced surgical technique with total
      mesorectal excision, circumferential tumor margin, and lymph node dissection that
      may help to better define a subset of stage II rectal cancer patients in which
      pelvic radiation may be safely omitted.

PMID- 17178293
TI  - Combined-modality strategy for gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumor (GIST) is the most common nonepithelial tumor of
      the gastrointestinal tract. The majority of these tumors stain positive for the
      CD117 antigen to the KIT protein and have become a well-documented clinical
      entity. The dysregulated KIT protein is oncogenic and is an ideal target for
      imatinib, a KIT-selective inhibitor. Clinical trials of imatinib for metastatic
      GIST have shown either partial response or long-duration stable disease in 82% of
      patients. Trials addressing the efficacy of adjuvant imatinib following resection
      for high-risk primary GIST are awaiting results. The neoadjuvant preoperative use
      of imatinib to provide pharmacologic debulking and long-term disease control is
      also nearing completion in a clinical trial. This trial has the potential of
      addressing whether the combination of surgery and imatinib can enhance organ
      sparing, decrease drug resistance, and prolong disease-free and overall survival.
      The continued study of combining surgery and a target-specific agent for
      malignant GIST will be a valuable reference for future strategies combining
      surgery and targeted treatment in other solid tumors.

PMID- 17178296
TI  - Applications of a duplex reverse transcription polymerase chain reaction and
      direct immunofluorescence assay in comparison with virus isolation for detection
      of influenza A and B.
AB  - A duplex reverse transcription polymerase chain reaction (RT-PCR) and direct
      immunofluorescence assays (DFAs) were evaluated for detection of influenza types
      A and B in comparison with virus isolation in Madin-Darbin canine kidney cells.
      Four hundred four nasal wash were collected from individuals presenting with
      acute respiratory symptoms during 2001 to 2003 influenza seasons. According to
      the reference method, 78 (19.3%) samples were infected by influenza virus: 46
      were type A and 32 type B. The overall concordance between the 3 assays was 96%,
      with 317 negative and 71 positive samples in all tests. RT-PCR reached 92.3%
      sensitivity and 98.5% specificity, and for DFA, the corresponding values were
      93.6% and 97.2%, respectively. DFA and RT-PCR could be applied in different
      routine settings, resulting as an advantage compared with virus isolation: DFA
      provides rapid results for clinical purposes, but RT-PCR allows running more
      samples, an important concern in early pandemic circumstances.

PMID- 17178294
TI  - Hepatocellular carcinoma: molecular biology and therapy.
AB  - Advanced and metastatic hepatocellular carcinomas (HCC) are challenging to treat,
      and no cytotoxic agents have impacted survival. The underlying liver cirrhosis
      that commonly accompanies HCC provides an additional challenge; indeed,
      functional scoring of cirrhosis and HCC is a critical component of patient
      evaluation. Currently, the molecular biology and pathogenesis of HCC are being
      increasingly investigated, which may lead to better understanding of the
      evolution of the disease, especially differing etiologies and identification of
      survival genes that may affect outcome. Early studies of targeted therapies in
      HCC have shown disease stabilization, and an increased understanding of the
      mechanism(s) of these novel agents combined with correlative studies may lead to
      the identification of an active agent or combination of agents that impacts the
      natural history of HCC.

PMID- 17178297
TI  - Bacterial, yeast, parasitic, and viral enteropathogens in HIV-infected children
      from Sao Paulo State, Southeastern Brazil.
AB  - We present here the frequency of enteropathogens in an HIV-infected children
      group and investigate their correlation with clinical and sociodemographic
      characteristics by collecting 100 stool samples from 55 HIV-seropositive
      Brazilian children. All specimens were processed according to standard methods
      for bacterial and yeast detection. A commercially available enzyme-linked
      immunosorbent assay was used to detect protozoan, and to perform virus detection,
      molecular tests were applied. Consumption of raw vegetables and fruits and severe
      immunosuppression were significantly associated with diarrhea. Cryptosporidium
      parvum was the commonest enteropathogen, followed by Candida albicans,
      enteropathogenic Escherichia coli, and astrovirus. The number of potential
      pathogenic agents identified in fecal specimens in asymptomatic HIV-seropositive
      infants is high, which raises the need for additional investigation in this area
      as well as in other Brazilian regions.

PMID- 17178299
TI  - Early-onset neutropenia is a risk factor for Candida colonization in very low
      birth-weight neonates.
AB  - Neutropenia is a major risk factor for bacterial colonization and sepsis in
      preterm neonates in the neonatal intensive care unit (NICU), but little is known
      about its relationships with candidal colonization (CC) in these settings. We
      performed a case-control study on neonates with birth weight of <1500 g admitted
      to our NICU during a 7-year period (1996-2003, N = 585). Through database search,
      infants with early-onset neutropenia (EON) (n = 68, group A) were identified and
      1:1 matched with controls without EON (n = 68, group B). Microbiologic data from
      weekly surveillance cultures were examined to determine the presence and
      intensity of CC. Groups A and B were similar clinically and demographically. All
      group A neonates recovered from EON before the 8th day of life. Incidence of CC
      in the 1st month of life (at least 1 site) was significantly higher in group A
      (61.8% versus 35.3%, P = 0.002) and was not modified by treatment with
      recombinant granulocyte colony-stimulating factor. The same was true of CC
      intensity, expressed as the number of sites affected (P = 0.002). Incidence of
      candidal sepsis, mortality rates, and relative frequencies of the various
      subspecies of Candida among the isolates did not significantly differ between the
      2 groups. In conclusion, EON in preterm neonates is a significant, independent
      risk factor for CC. Larger, prospective, adequately powered studies should verify
      whether increased CC related to neutropenia may translate into a similar
      increased occurrence of candidal sepsis in these settings.

PMID- 17178298
TI  - Comparison of the NOW Influenza A & B, NOW Flu A, NOW Flu B, and Directigen Flu
      A+B assays, and immunofluorescence with viral culture for the detection of
      influenza A and B viruses.
AB  - To evaluate the Binax NOW Influenza A & B combination assay, we tested upper
      respiratory tract samples in parallel with the Binax NOW Flu A and Binax NOW Flu
      B assays, the Becton-Dickinson Directigen Flu A+B assay, and immunofluorescence,
      and the results were compared with viral culture. Of the 521 samples tested,
      influenza A was cultured from 113 and influenza B from 6. There were no
      significant differences in the performance of all rapid antigen tests, with
      sensitivities of 53% to 59% for detecting influenza A compared with culture and
      immunofluorescence (80%). The sensitivities for all rapid tests were
      significantly higher for nasopharyngeal samples than for throat swabs. The Binax
      NOW Influenza A & B assay performed as well as other rapid assays. Commercial
      antigen detection assays are useful tools for the rapid diagnosis of influenza;
      however, confirmatory testing is always recommended. The use of nasopharyngeal
      samples for all rapid detection methods should be strongly encouraged.

PMID- 17178300
TI  - Serial sinus aspirate samples during high-dose, short-course levofloxacin
      treatment of acute maxillary sinusitis.
AB  - This study assessed daily aspirate samples from an indwelling sinus catheter
      during high-dose, short-course levofloxacin (750 mg daily x 5 days) treatment of
      acute maxillary sinusitis. Pathogens were isolated from 4 of 18 recruited
      patients. Bacteriologic eradication occurred within 24 h for 3 patients and 72 h
      for the 4th.

PMID- 17178301
TI  - Overview of stroke care in the United States and beyond.

PMID- 17178302
TI  - The Paul Coverdell National Acute Stroke Registry (PCNASR): a public health
      initiative.

PMID- 17178303
TI  - Analysis of data-collection methods for an acute stroke care registry.
AB  - This study aims to assess and compare the completeness and reliability of data
      collected by prospective and retrospective methods for the Paul Coverdell
      National Acute Stroke Registry. The prototypes consisted of eight states that
      used the same data elements but differed in their collection approach. Three
      prototypes employed retrospective case ascertainment (n=1218), and five
      prototypes used prospective or a combination of prospective and retrospective
      case ascertainment (n=1602). RTI International performed an audit analysis of the
      eight prototypes. Completeness, exact match, and discrepancy analyses were
      performed with data elements grouped into 12 categories for this analysis. A
      sample of 2820 (37.6%) from a total of 7494 records from 91 hospitals was
      studied. The "in-hospital complications" section had the highest percentage of
      completeness (99.6%), followed by "demographic data" (97.7%), and "in-hospital
      diagnostic procedures" (93.4%). The section with the lowest percentage of
      completeness was "thrombolytic treatment" (53.5%), followed by "reasons for
      nontreatment with thrombolytics" (57.1%), and "signs and symptoms onset" (63.5%).
      Across all prototype elements, exact matches with audit data ranged from 62.8% to
      95.9%. Documentation of the date/time of stroke onset and of arrival in the
      emergency department had a high number of discrepancies with audit data, with
      exact match percentages of 69.7% and 64.5%, respectively. No significant
      difference was found between retrospective and prospective case ascertainment in
      completeness or matching with audit data. Combined retrospective and prospective
      data-collection approaches for different types of data elements may be best in
      terms of both completeness and accuracy.

PMID- 17178306
TI  - Use of a prototype acute stroke registry to improve care: profile of receptive
      stroke programs.
AB  - A Wave-II Paul Coverdell Prototype Acute Stroke Registry collected data from 16
      hospitals of various sizes and types in Oregon. The goal of this study was to
      identify whether particular process or structural characteristics of stroke
      programs in these hospitals were related to the use of reports from the prototype
      registry to improve care. Researchers surveyed hospitals to ask whether ongoing
      data completeness reports and monthly comparative quality reports were used to
      make changes in the acute care process. These self-reports were then confirmed by
      using the registry data to construct objective run-chart measures over 12 months.
      Results showed several programmatic characteristics that distinguished programs
      that used quality reports to make improvements. Hospitals that ignored monthly
      reports of key performance indicators showed either zero or one positive trend
      across seven preselected quality indicators. This finding is in contrast to the
      range of one to four positive changes in quality indicators for report users.
      Three main characteristics seem to define report users who could translate
      ongoing findings into potential care improvements: (1) documentation of care
      processes across departments; (2) access to local or remote stroke teams; and (3)
      data-collection experiences such as clinical trials, National Institutes of
      Health Stroke Scale (NIHSS), and outcome feedback. This study could lead to a
      better understanding as to which characteristics of stroke programs are most
      important for making rapid improvements for stroke care.

PMID- 17178304
TI  - The Paul Coverdell National Acute Stroke Registry: initial results from four
      prototypes.
AB  - BACKGROUND: This paper summarizes the experiences of the Paul Coverdell National
      Acute Stroke Registry first four prototype registries in Georgia (GA),
      Massachusetts (MA), Michigan (MI), and Ohio (OH), and includes information on
      their sampling design, case ascertainment, and data collection methods, as well
      as some key findings. METHODS: Using a combination of different sampling methods,
      each prototype obtained a representative statewide sample of hospitals. Acute
      stroke admissions were identified through prospective (MA, MI) or retrospective
      (GA, OH) methods. A common set of case definitions and data elements were used by
      each registry. Weighted site-specific frequencies and 95% confidence intervals
      were generated for each outcome. A summary estimate, representing a weighted
      average of the four site-specific estimates, was also calculated. RESULTS: Of the
      total 6867 admissions, 1487 (21.6%) were from the GA registry, 1206 (17.6%) from
      MA, 2566 (37.4%) from MI, and 1608 (23.4%) from the OH prototype. Just less than
      60% of admissions were ischemic strokes (site-specific estimates ranged from 52%
      to 70%), with transient ischemic attack (18.5%) and intracerebral hemorrhage
      (8.8%) making up most of the remainder. Twenty-one percent of patients admitted
      were younger than 60 years of age, and 55.3% were women. The proportion of black
      subjects varied from 7.1% (MI) to 30.6% (GA). Twenty-three percent of admissions
      arrived at the emergency department within 3 hours of onset. Overall 4.5% of
      ischemic stroke admissions were treated with recombinant tissue plasminogen
      activator; site-specific treatment rates were 3.0% (GA), 3.2% (OH), 3.4% (MI),
      and 8.5% (MA). Only a small minority of treated patients (range, 10.8% [OH] to
      19.6% [MI]) received recombinant tissue plasminogen activator within the
      recommended 1 hour door-to-needle time. A minority of eligible subjects were
      screened for dysphagia (45.4%), underwent lipid testing (33.6%), or received
      smoking-cessation counseling (21.4%). In contrast, compliance with antithrombotic
      treatments at discharge was high (91.5%). CONCLUSIONS: A minority of acute stroke
      patients are treated according to established guidelines. Quality improvement
      interventions, targeted primarily at the healthcare systems level, are needed to
      improve acute stroke care in the United States.

PMID- 17178305
TI  - Why are eligible thrombolysis candidates left untreated?
AB  - BACKGROUND: Despite proven efficacy, thrombolytics are used in a minority of
      eligible candidates. Because some of the exclusion criteria are vague, relying on
      documented contraindications could disguise biases in usage. This study sought to
      identify barriers to tissue-type plasminogen activator (tPA) treatment among
      eligible patients with acute ischemic stroke. METHODS: The study prospectively
      identified all patients with an initial diagnosis of ischemic stroke arriving
      within 2.5 hours of symptom onset at 11 hospitals participating in the Centers
      for Disease Control and Prevention-sponsored California Acute Stroke Prototype
      Registry during two 3-month periods in 2002 and 2003. Potential risk factors for
      nontreatment with thrombolytics among patients categorized as eligible were
      examined, based on directly documented contraindications. Analyses were repeated
      after reclassification of eligibility based on record review. RESULTS: Of 625
      patients with ischemic stroke, 126 (20%) arrived at the emergency department
      within 2.5 hours of symptom onset. Based on direct documentation, 72 (11.5% of
      all patients; 57% of in-time arrivals) were eligible for thrombolysis; 32 (44% of
      eligible patients) who received tPA within the 3-hour time window and 40 who did
      not receive thrombolytic medications despite having no documented
      contraindication to treatment. Factors predictive of nontreatment were older age
      (p=0.0005), later arrival (p=0.004), and admittance to a non-academic hospital
      (p=0.03). After record review, slightly fewer patients (n=61) were deemed
      eligible, with a tPA treatment rate of 52% among those eligible. Older age
      (p=0.002) and later arrival (p=0.002) continued to be predictive of nontreatment
      with thrombolytics after reclassification. CONCLUSIONS: Even when more
      comprehensive eligibility standards are applied, older age and later hospital
      arrival are associated with nontreatment with thrombolytics.

PMID- 17178307
TI  - Data feedback for quality improvement of stroke care: CAPTURE Stroke experience.
AB  - BACKGROUND: Feedback on "quality indicators" collected from chart audit is a
      widely used quality-improvement strategy. Skeptics argue that temporal change in
      practice patterns or improvement of documentation as a result of implementation
      of chart audit can affect change in quality indicators rather than change in
      practice due to feedback. This study compared the effectiveness in quality
      improvement for stroke care of chart audit and feedback versus chart audit only.
      METHODS: Data were examined on quality indicators constructed from the
      performance measures abstracted from chart audit for 1953 stroke patients
      admitted to 13 hospitals. Seven of the 13 hospitals were provided with feedback
      on quality indicators from baseline audit, and 6 hospitals had chart audit only.
      RESULTS: Least-squares estimation was used to estimate the adjusted mean change
      in quality indicators between follow-up and baseline audits and differences in
      mean change between feedback and nonfeedback groups. Differences in adjusted mean
      change (with 90% confidence interval) were: deep vein thrombosis prophylaxis,
      8.46 (-9.46 to 26.38); dysphagia screening, -3.78 (-21.37 to 13.81);
      antithrombotic therapy within 48 hours of hospitalization, 3.63 (-6.59 to 13.84);
      discharged on antithrombotic, -0.31 (-6.26 to 5.63); patients with atrial
      fibrillation discharged on warfarin/coumadin, 44.73 (-13.14 to 102.60); lipid
      screening, 19.93 (2.99 to 36.86); and smoking counseling, 17.47 (-12.13 to
      47.08). CONCLUSIONS: Although not statistically significant, results suggest a
      potential for improvement with data feedback. There is a need for evaluation of
      the effectiveness of a multifaceted approach in a community setting.

PMID- 17178308
TI  - Documentation of stroke onset time: challenges and recommendations.

PMID- 17178309
TI  - International experience in stroke registries: lessons learned in establishing
      the Registry of the Canadian Stroke Network.
AB  - This paper discusses the early lessons learned in establishing the Registry of
      the Canadian Stroke Network (RCSN), particularly the pitfalls related to the
      requirement for informed patient (or surrogate) consent for inclusion in the
      registry. The need for stroke registries to collect accurate data that are
      representative of all patients with acute stroke in a given community is
      emphasized, and how the current methodology strives to reach this goal is
      outlined.

PMID- 17178310
TI  - International experience in stroke registries: German Stroke Registers Study
      Group.

PMID- 17178311
TI  - International experience in stroke registry: Japanese Stroke Databank.

PMID- 17178312
TI  - International experience in stroke registries: Korean Stroke Registry.

PMID- 17178313
TI  - Quality of acute stroke care improvement framework for the Paul Coverdell
      National Acute Stroke Registry: facilitating policy and system change at the
      hospital level.
AB  - The Paul Coverdell National Acute Stroke Registry prototypes baseline data
      collection demonstrated a significant gap in the use of evidenced-based
      interventions. Barriers to the use of these interventions can be characterized as
      relating to lack of knowledge, attitudes, and ineffective behaviors and systems.
      Quality improvement programs can address these issues by providing didactic
      presentations to disseminate the science and peer interactions to address the
      lack of belief in the evidence, guidelines, and likelihood of improved patient
      outcomes. Even with knowledge and intention to provide evidenced-based care, the
      absence of effective systems is a significant behavioral barrier. A program for
      quality improvement that includes multidisciplinary teams of clinical and quality
      improvement professionals has been successfully used to carry out redesign of
      stroke care delivery systems. Teams are given a methodology to set goals, test
      ideas for system redesign, and implement those changes that can be successfully
      adapted to the hospital's environment. Bringing teams from several hospitals
      together substantially accelerates the process by sharing examples of successful
      change and by providing strategies to support the behavior change necessary for
      the adoption of new systems. The participation of many hospitals also creates
      momentum for the adoption of change by demonstrating observable and successful
      improvement. Data collection and feedback are useful to demonstrate the need for
      change and evaluate the impact of system change, but improvement occurs very
      slowly without a quality improvement program. This quality improvement framework
      provides hospitals with the capacity and support to redesign systems, and has
      been shown to improve stroke care considerably, when coupled with an Internet
      based decision support registry, and at a much more rapid pace than when
      hospitals use only the support registry.

PMID- 17178314
TI  - Designing a sustainable national registry for stroke quality improvement.
AB  - Several studies have shown wide variations in the delivery of hospital-based care
      to patients with acute ischemic stroke. The findings of these studies suggest
      that recommendations drawn from published evidence-based or consensus-based
      guidelines are implemented inconsistently. Although rates of adherence to stroke
      quality indicators can be increased through the use of targeted quality
      improvement (QI) efforts, stroke QI programs are still in their infancy. Current
      stroke QI programs are often highly variable and poorly coordinated, rely on
      differing definitions of key data elements and/or indicators, and are challenging
      to implement and sustain in resource-constrained healthcare environments. Key
      barriers to long-term success of these programs include inadequate funding at the
      local and national level, lack of infrastructure to support electronic data
      capture for QI as part of the process of patient care, lack of a single
      clearinghouse for uniform data definitions and performance indicator
      descriptions, competing survey instruments to monitor hospitalized stroke care,
      and constraints on inpatient and post-discharge data collection imposed by the
      new Federal Health Insurance Portability and Accountability Act Privacy Rule. In
      addition, the competing needs of registry activities (e.g., complete case
      ascertainment) versus QI efforts (e.g., incremental tests of change) must be
      balanced. Potential solutions include: (1) financial incentives to healthcare
      providers and institutions for participation in QI initiatives; (2) financial
      incentives to healthcare providers and institutions for measurable improvements
      in care; (3) mandatory data reporting on key measures of stroke care; and (4)
      promotion of active and sustainable collaborations among key stakeholders
      including healthcare providers (e.g., physicians, nurses), healthcare
      organizations (e.g., hospitals, physicians' groups), quality improvement
      organizations, health payers and insurers, public health departments, and state
      and federal health agencies to create a single national stroke registry for
      stroke QI.

PMID- 17178316
TI  - Primary certification in vascular surgery: what does this really mean?
AB  - A primary certificate for vascular surgery has recently been approved by both the
      American Board of Medical Specialties and the Accreditation Council for Graduate
      Medical Education. This new training paradigm will allow training and
      certification in vascular surgery without first obtaining American Board of
      Surgery certification in general surgery. There are now several pathways ways to
      obtain vascular surgery certification, which are described in this article. All
      programs require an MD or DO degree from an institution accredited by the Liaison
      Committee of Medical Education or by the American Osteopathic Association.
      Graduates of schools of medicine from countries other than the United States or
      Canada must present evidence of final certification by the Education Commission
      for Foreign Medical Graduates.

PMID- 17178317
TI  - New training paradigms and program requirements.
AB  - Specialized training in vascular surgery evolved over the second half of the 20th
      century and continues to do so in 2006. Apprenticeship-style training in the
      1960s and 1970s gave way to formal curriculum- and case-based programs created in
      the 1980s to improve the quality and consistency of vascular care. Recent
      developments have resulted in the Accreditation Council for Graduate Medical
      Education's approval of additional training pathways leading to certification by
      the American Board of Surgery. This article summarizes the history of vascular
      surgery training in the United States and describes the four types of currently
      approved programs--Standard, Early Specialization, Independent, and Integrated-
      for specialty training in vascular surgery. These are the only programs that can
      lead to American Board of Surgery certification in vascular surgery.

PMID- 17178318
TI  - Analysis of the current applicant pool to vascular surgery: who are they and
      where do they come from?
AB  - There is a manpower crisis in vascular surgery. There may be too few vascular
      surgeons to meet the demands imposed by the aging of the "Baby-Boom" generation.
      More than 20% of vascular surgery positions were not filled through the match in
      2004 and 2005. The number of vascular surgery training positions has doubled in
      the past 15 years, based on manpower studies projecting a need for additional
      vascular surgeons. During the same time period, the number of vascular surgery
      applicants has remained static. In addition, the proportion of international
      medical graduates has increased significantly. Furthermore, medical students
      appear to be selecting "lifestyle-friendly" specialties, such as emergency
      medicine, radiology, ophthalmology, anesthesiology, and dermatology, with
      increasing frequency. Approximately 60% of undergraduates in the United States
      and almost 50% of graduating medical students are currently women. Yet only about
      25% of general surgery residents and less than 20% of current vascular surgery
      trainees are women. Strategies to expand the applicant pool for vascular surgery
      are needed and discussed in this article.

PMID- 17178319
TI  - Choice of vascular surgery as a specialty: what is important?
AB  - In the last few years, the Association of Program Directors in Vascular Surgery
      has become increasingly concerned that the number of applicants to vascular
      surgery residencies has remained stable, while the number of available positions
      has increased substantially and quality of applicants has diminished. What
      factors are relevant for residents and medical students whether they do or do not
      choose vascular surgery as a specialty? In this article, we cite specific reasons
      that played key roles in this decision-making process, based on various surveys
      and reports addressing this issue. Technical aspects of vascular surgery, the
      role of mentors, and lifestyle issues were shown to be critical factors in the
      choice of potential trainees. Different training paradigms were also shown to be
      favored by residents and students, depending on their level of training. The
      findings in these surveys have helped vascular surgery program directors devise
      new and innovative training paradigms and to develop strategies to attract future
      trainees.

PMID- 17178320
TI  - Vascular surgery training: is there enough case material?
AB  - In recent years, vascular surgery fellowships have changed substantially to meet
      the requirements for interventional as well as open surgical training. Data from
      the Residency Review Committee for Surgery indicate that the average vascular
      fellow performed fewer than 15 interventional procedures in 2000, but that this
      volume had increased to more than 200 interventional procedures by 2005, an
      increase of 255%. During the same interval, there was a slight (4%) decrease in
      the average number of major open vascular reconstructions performed. In 2005, the
      average vascular fellow performed 450 primary procedures, nearly equally divided
      between open and interventional cases. Selected open operations, such as aortic
      aneurysm repair, have decreased in volume due to the substitution by endovascular
      procedures. Operative volume for vascular fellows has been preserved in part by a
      19% reduction in major vascular operations performed by general surgery
      residents. However, with added overall volume due to the increased prevalence of
      vascular disease in the aging population, there appears to be adequate case
      material to train future vascular surgeons, as long as less commonly performed
      operations continue to be focused on vascular trainees.

PMID- 17178321
TI  - Advanced training in vascular surgery: how does it need to change?
AB  - Fellowship training in vascular surgery over the last several decades has
      typically involved 1 to 2 years of clinical training incorporating open surgical
      techniques, some noninvasive vascular diagnostic laboratory, outpatient and
      inpatient experiences, occasionally basic science research, and more recently
      training in endovascular procedures. In order to meet the projected increased
      need for vascular care in the future, vascular surgery training needs to undergo
      both structural and content modifications if the field is to stay at the
      forefront in caring for the patient with vascular disease. This article addresses
      these issues and potential solutions.

PMID- 17178322
TI  - Advanced endovascular training for vascular residents: what more do we need?
AB  - In the 25 years that formalized vascular surgery training and certification has
      been, in effect, the treatment of patients with peripheral vascular disease has
      undergone dramatic changes, largely due to the emergence of a wide variety of
      endoluminal techniques and devices that enable minimally invasive treatment of
      conditions that formerly required operative intervention. Unfortunately, vascular
      surgeons, for the most part, were painfully slow to embrace these new and
      evolving technologies, which became increasingly complex as they expanded to
      treat virtually all vascular maladies in all peripheral vascular territories. Not
      surprisingly, this left vascular surgeons disadvantaged relative to other
      disciplines for whom these techniques were more familiar, and we have spent the
      better part of the last decade playing catch-up to master them and regain our
      role as the only specialty qualified to offer all types of therapies to our
      patients with vascular disease. This has caused some to question what changes
      need to be made in our vascular surgery training paradigm for our new trainees to
      attain and maintain a preeminent role in the evaluation and treatment of patients
      with peripheral vascular disease. While the knee-jerk response is to consider
      special or supplemental training programs for these advanced techniques, or even
      certificates of added qualifications for the more challenging of them, such as
      carotid stenting, we believe that all that is really needed is for the vascular
      surgical community as a whole, and particularly those faculty in training
      programs, to truly embrace these new technologies and apply them to the patients
      they are already rendering care to. Given the prevalence of vascular disease and
      overall wealth of clinical material already present in most training programs,
      the simple willingness to apply endoluminal therapies to our existing patient
      populations is all that would really be needed to insure that all future
      graduates of vascular surgery training programs are fully competent in all of the
      current endoluminal therapies and well-positioned to continue to evolve with the
      field. The real question to be considering, which is beyond the focus of this
      article, is how we are to maintain our open surgical skills in the era of
      minimally invasive treatment of vascular disease.

PMID- 17178323
TI  - Training in vascular medicine for vascular surgeons--what is it and how will we
      accomplish it?
AB  - The goal of vascular surgery training program should be the training of a
      complete vascular surgeon proficient not only in the management of established
      peripheral vascular disease but also in the prevention of the atherosclerotic
      process through management of risk factors. In addition, vascular surgeons should
      develop expertise in the treatment of nonatherosclerotic arterial disease,
      nonoperative management of acute and chronic venous disease, lymphedema, and the
      treatment of various coagulation disorders. To accomplish these goals, we should
      establish a comprehensive, patient-centered vascular medicine curriculum and
      appropriate methods for its implementation.

PMID- 17178324
TI  - Training and credentialing in vascular laboratory diagnosis.
AB  - Physicians interpreting vascular laboratory studies require proper training and
      credentialing. It is suggested minimal training requirements include but, may not
      be limited to, the following: a medical license and knowledge of the fundamental
      concepts of vascular physiology, anatomy, and ultrasound physics. In addition,
      there should be evidence of training in vascular diagnostics beyond medical
      school, clinical experience in the treatment of vascular disease, supervised
      experience with specific numbers of vascular laboratory interpretations in the
      areas in which the physician wishes to interpret, and evidence of ongoing
      continuing medical education (CME) in noninvasive vascular diagnostics.
      Credentialing requirements are determined locally, but it is suggested that
      successful completion of the American Registry of Diagnostic Medical
      Sonographers' Registered Physician in Vascular Interpretation (RPVI) examination
      will provide evidence of core knowledge of vascular laboratory topics that is
      independent of medical or surgical specialty. Completion of the RPVI exam,
      completion of core training requirements, along with ongoing CME, is a basis for
      establishing minimal requirements for interpretation of vascular laboratory
      studies.

PMID- 17178325
TI  - Core training in surgery: what does it need to include?
AB  - Core training for surgeons in any surgical specialty should include education in
      the relevant basic science knowledge, training in fundamental diagnostic skills,
      the development of surgical technical skills and considerable experience in
      patient care. However, for a number of reasons it is no longer acceptable to
      guide such training based only on such broad goals, not the least of which is the
      advent of resident duty-hour limitations that make it unrealistic to expect
      residents to simply acquire, by random observation and participation, all of the
      important elements of their future practices. Rather, it is necessary to provide
      a curriculum of learning opportunities specifically structured to allow them to
      gain the requisite knowledge and skills. Thus, the curriculum for the core
      surgical training of future vascular surgeons should be based on a very specific
      learning objectives, stating what information is to be learned or what action is
      to be done, under what conditions they are to be performed, and what criteria
      will be used to ascertain the acquisition of the necessary knowledge or skill.
      Next, the best methods of instruction, including reading materials, lectures, and
      exposure to specific surgical procedures must be defined and the appropriate
      instructional materials identified, selecting the best of existing materials or,
      if necessary, creating them. Finally, the residents' acquisition of knowledge and
      skills must be assessed. Previously this occurred through a loose combination of
      performance evaluations from clinical rotations, faculty group discussions, and
      annual in-training exams culminated in the American Board of Surgery
      certification process. Now evaluation must relate to specific educational
      objectives. This is all a daunting task currently being undertaken by vascular
      surgery program directors, albeit with input from the Residency Review Committee
      and the Vascular Surgery Board of the American Board of Surgery. Eventually,
      overall surgical curriculum will evolve to satisfy these educational ground
      rules, but currently it is very much a work in progress in most programs.

PMID- 17178326
TI  - Early specialization in surgical training: an old concept whose time has come?
AB  - The complexity of surgical science and surgical patient care is increasing at an
      accelerating pace. As a consequence, many areas of surgical practice once within
      the scope of general surgery have evolved into distinct specialties with unique
      advanced training requirements. Given this evolution in surgical specialization,
      many have considered that our current model of surgical training--a 5-year
      residency in general surgery, followed by any of a wide variety of fellowships to
      acquire refined, advanced training--is due for major restructuring. The current
      debate focuses on the benefits and potential disadvantages of earlier
      differentiation of surgeons into specialty training pathways. The structure of
      surgical training, including the definition of core surgical training and the
      optimal structure to introduce advanced specialty training tracks, is the central
      issue in this debate. This article reviews the question and current deliberations
      of the stakeholders in graduate surgical education and training.

PMID- 17178327
TI  - How will the introduction of primary certificate training programs change
      vascular surgery training programs?
AB  - New requirements for vascular surgery training allow several routes to Board
      eligibility in the specialty. Individuals can enter vascular residency directly
      from medical school, after 3 years of surgical residency, or after completion of
      the traditional 5 years of surgery training. Vascular surgery program directors
      will be faced with the challenges of obtaining institutional support, designing
      an acceptable educational program, and working closely with the general surgery
      program director to ensure both programs are successful. Faculty in the vascular
      program may find working with residents right out of medical school or after only
      3 years of surgery training to be a challenge, especially in terms of developing
      the requisite technical skills. Residents must be able to demonstrate mastery of
      the six competencies in addition to the skills of vascular surgery. Because, in
      some ways, this new vascular training scheme is an experiment in redesigning all
      surgical education, the vascular community will need to carefully evaluate the
      results by monitoring the practices of those who graduate from these programs.

PMID- 17178328
TI  - Vascular surgery training after primary certification: where we go from here.
AB  - Program directors in vascular surgery have an increasingly complex set of
      responsibilities in the management of a vascular surgery residency, now that
      primary certification has been approved for vascular surgery and new training
      paradigms have been created in addition to the previous sequential training and
      certification in both general and vascular surgery. With the availability of new
      training paradigms, such as the 3+3 curriculum or entrance into a vascular
      residency program of 5 or 6 years directly out of medical school, the program
      director will become responsible for ensuring adequate training in basic surgical
      principals as well in the management of vascular pathology. Areas of added
      responsibility will include recruiting trainees, maintaining training case
      volumes, developing effective educational curricula and certifying the quality of
      the residents. This article discusses these tasks in detail, identifying special
      problem areas, such as changing lifestyle expectations, particularly in
      recruiting women, now approaching one half of medical students; expansion to meet
      the increasing need for vascular surgeons in the future as the population ages;
      funding vascular fellowship training; maintaining open surgical case loads while
      providing the facilities and supervision for adequate endovascular surgical
      training; providing a useful experience in both noninvasive vascular diagnosis
      and nonoperative management of vascular disease--in short, an experience that
      will result in Board certification and obtaining hospital privileges and a career
      that satisfies their choice of vascular surgery as a specialty.

PMID- 17178329
TI  - Long-term change in cholesterol in relation to inflammation-sensitive plasma
      proteins: a longitudinal study.
AB  - PURPOSE: The nature of the relationship between inflammation and elevated serum
      lipid levels is incompletely understood. This longitudinal study explores whether
      elevated levels of inflammation-sensitive plasma proteins (ISPs) are a risk
      factor for developing increased cholesterol and triglyceride levels. METHODS:
      Five ISPs (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and
      ceruloplasmin) were measured in a population-based cohort of nondiabetic healthy
      men aged 38 to 50 years at baseline. Subjects were reexamined after a mean of 6.2
      years. The development of hypercholesterolemia (cholesterol>or=6.5 mmol/L
      [>or=251 mg/dL]) and hypertriglyceridemia (triglycerides>or=2.3 mmol/L [>or=204
      mg/dL]) during follow-up was studied in relation to the number of elevated levels
      of ISPs (i.e., in the top quartile). RESULTS: Of men with initially normal
      cholesterol levels (<6.5 mmol/L; n=2224), proportions of men with no, one, two,
      and three or more elevated ISP levels at baseline who developed
      hypercholesterolemia were 12%, 13%, 16%, and 20%, respectively (p for
      trend=0.0002). This relationship remained significant after adjustments for
      cholesterol level at baseline and other confounding factors. The relationship
      between ISP levels and future hypertriglyceridemia was attenuated and
      nonsignificant after adjustments for confounding factors. CONCLUSION: In
      apparently healthy men with initially normal cholesterol levels, elevated ISP
      levels are a risk factor for development of hypercholesterolemia.

PMID- 17178330
TI  - Molecular testing in the management of cardiac transplant recipients: initial
      clinical experience.

PMID- 17178331
TI  - Is brain natriuretic peptide clinically useful after cardiac transplantation?
AB  - The clinical use of brain natriuretic peptide (BNP) in patients after cardiac
      transplantation remains to be defined. Over the last decade, a series of small
      studies have been performed to determine any potential use of this assay in the
      assessment of allograft function and prognosis. From the available evidence, it
      appears that a low BNP level in transplant recipients has a high negative
      predictive value for death. Why patients with higher BNP levels should be
      disadvantaged appears to be multifactorial. BNP titer may be influenced by severe
      rejection episodes and diastolic dysfunction, and possibly intracardiac pressure
      derangement. Although the concept of using a simple blood test to assess these
      patients sounds very attractive, further work is needed to define the exact role
      of this assay. Presently, it cannot be confirmed whether BNP can replace any of
      the current methods of assessing allograft performance and prognosis after
      transplantation.

PMID- 17178332
TI  - Utility of long-term surveillance endomyocardial biopsy: a multi-institutional
      analysis.
AB  - BACKGROUND: The utility of long-term endomyocardial biopsy surveillance in heart
      transplant recipients has been questioned. This study was undertaken to identify
      risk factors for late rejection and to examine the impact of different biopsy
      surveillance protocols on outcomes using the registry of the Cardiac Transplant
      Research Database. METHODS: The study group consisted of all adult patients who
      underwent heart transplantation at the 33 centers participating in this
      investigation between January 1, 1993 and January 1, 2002, survived past the
      second post-transplant year, and were followed-up by a defined surveillance
      biopsy protocol. RESULTS: During a follow-up that consisted of 24,137 patient
      years, 1,626 late rejections occurred. Shorter time since transplant, history of
      rejection, younger age and African-American ethnicity of the recipient were
      strong risk factors for late rejection. The practice of surveillance biopsy
      varied among institutions. Continued surveillance increased the rate of diagnosis
      of late rejection (RR = 1.3, p = 0.002). There was no reduction in the incidence
      of hemodynamically compromising rejection and no increase in survival in patients
      with long-term vs intermediate-term surveillance. Short-term surveillance was
      associated with an increased incidence of hemodynamically compromising rejection,
      particularly among high-risk patients, and increased mortality in African
      American patients. CONCLUSIONS: There are no apparent benefits from surveillance
      biopsy beyond 5 years post-transplant. Surveillance biopsy between 2 and 5 years
      post-transplant was found to reduce mortality in African-American recipients. Non
      African-American recipients at high risk for late rejection will likely benefit
      from surveillance up to 5 years post-transplant.

PMID- 17178333
TI  - Management of aortic insufficiency with continuous flow left ventricular assist
      devices: bioprosthetic valve replacement.
AB  - There are several methods for surgical management of aortic insufficiency in
      patients with end-stage congestive heart failure who are undergoing implantation
      of a left ventricular assist device (LVAD). To date, little is known about the
      long-term outcome of bioprosthetic valves for aortic insufficiency in patients
      with continuous flow LVADs. We report on two patients with bioprosthetic aortic
      valve replacement for aortic insufficiency at the time of HeartMate II LVAD
      insertion.

PMID- 17178334
TI  - A quantitative gene expression profile of matrix metalloproteinases (MMPS) and
      their inhibitors (TIMPS) in the myocardium of patients with deteriorating heart
      failure requiring left ventricular assist device support.
AB  - BACKGROUND: Mechanisms underlying the rapid deterioration of heart failure
      patients who subsequently require left ventricular assist device (LVAD) support
      are poorly understood. Matrix metalloproteinases (MMPs) and the tissue inhibitors
      of metalloproteinases (TIMPs) play a key role in myocardial remodelling and heart
      failure. We hypothesized that MMP and TIMP expression would be altered in these
      patients. METHODS: Quantitative polymerase chain reaction was used to measure
      myocardial messenger RNA levels of MMP1 to MMP14, TIMP1 to TIMP4, collagen I and
      collagen III in 24 dilated cardiomyopathy (DCM) patients with deteriorating
      clinical status who required LVAD support (LVAD Group) and in 7 stable DCM
      patients undergoing transplantation without need for LVAD support (Tx Group).
      RESULTS: Levels of MMP1, MMP8 and TIMP4 were higher in the LVAD Group compared
      with the Tx Group (188% +/- 141%, 646% +/- 432%, and 66% +/- 33% higher,
      respectively, p < 0.05) whereas MMP2, MMP9, MMP10, MMP11, and MMP14 levels were
      similar. MMP3, MMP7, MMP12, and MMP13 were undetectable. All TIMPs were generally
      higher in the LVAD group, but only TIMP4 reached significance. Collagen I and III
      were not altered. We tested for correlations between MMP and TIMP expression with
      myocardial cytokine levels. MMP8 correlated positively with interleukin-6 and
      interleukin-1beta, suggesting a link between cytokines and MMPs in these
      patients. CONCLUSIONS: The data show that high myocardial collagenase (MMP1 and
      MMP8) expression without compensatory changes in collagen or TIMP expression is a
      feature of patients requiring LVAD support. This may be linked in part to
      elevated cytokine expression and suggests collagenase activity may be an
      important therapeutic target in deteriorating heart failure.

PMID- 17178335
TI  - Cardiac re-transplantation in pediatrics: a multi-institutional study.
AB  - BACKGROUND: Cardiac re-transplantation (re-Tx) among pediatric recipients remains
      controversial. The purpose of this study is to use the Pediatric Heart Transplant
      Study (PHTS) database to investigate the incidence of re-Tx and analyze the risk
      factors and outcomes after transplantation among children. METHODS: The PHTS
      database was reviewed for all subjects <or=18 years of age at the time of primary
      transplant and re-Tx from January 1, 1993 through December 31, 2004. Multivariate
      analyses in the hazard-function domain were used to identify risk factors for re
      Tx and for mortality after re-Tx. RESULTS: Risk factors for re-Tx include
      ventilator support, African-American ethnicity and elevated creatinine. Patient
      survival was inferior to that after primary transplantation (PTx) with 1-, 3- and
      5-year survival probability after re-Tx of 80%, 69% and 60%, respectively (p =
      0.04). Patients re-transplanted for graft coronary artery disease fared better
      than those re-transplanted for early graft failure. A shorter time period between
      PTx and re-Tx was a significant risk factor for survival according to univariate
      analysis. However, risk factors for death after re-Tx by multivariate analysis
      included only early graft failure and rejection during PTx. CONCLUSIONS: Survival
      after pediatric re-Tx is inferior to that after PTx. Re-transplantation for graft
      failure and rejection are associated with high relative risks for death. Given
      the limitations of donor availability, re-Tx for early graft failure and
      rejection appear contraindicated but appears acceptable for those who have
      survived >or=1 year after their PTx, especially those with graft coronary artery
      disease.

PMID- 17178336
TI  - Identification of non-HLA target antigens recognized after lung transplantation.
AB  - BACKGROUND: It has become evident that, besides cellular allogeneic immune
      responses against airway epithelial cells (AEC), humoral responses also
      contribute significantly to the pathogenesis of bronchiolitis obliterans syndrome
      (BOS) after lung transplantation (LTx). Antibody responses against transplanted
      lungs are directed against HLA and non-HLA antigens, but the identity of the
      latter antigens is presently unknown. METHODS: The main purpose of this study is
      to identify non-HLA target antigens on donor lungs recognized by patients'
      antibodies after LTx. Serum samples were taken before and 6 months after lung
      transplantation from 11 patients (4 men and 6 women, median age 44 years, range
      18 to 63 years). Protein expression libraries were made from the luminal side
      containing AEC of discarded the donor bronchus, which was snap frozen in liquid
      N(2) during the organ harvesting procedure. Subsequently, all sera were analyzed
      for reactivity against library-encoded antigens by serologic analysis of
      recombinant cDNA expression libraries (SEREX). Recognized gene products were
      sequenced and analyzed by the NCBI/BLAST server. RESULTS: From a total of +/-3 x
      10(4) gene products analyzed, six different non-HLA antigens were recognized by
      individual patient sera. Gene analysis indicated that they consisted of both
      polymorphic (PSMC4, F3, LOC284058, PLUNC, ZNF33A) and non-polymorphic (XP_931864)
      antigens. Cross-sectional analysis indicated that some antigens were recognized
      by 4 of 10 patient sera tested. CONCLUSIONS: Antibodies directed against non-HLA
      antigens are present after LTx, and can be identified using the SEREX technique.
      Identification of target antigens recognized after LTx will improve our
      understanding of the pathogenesis of BOS. Monitoring of the antibody response may
      be used to predict BOS.

PMID- 17178337
TI  - Predictors of decline in renal function after lung transplantation.
AB  - BACKGROUND: Survival after lung transplantation has improved, but with the
      consequence that long-term toxicities of treatment are of growing importance. In
      particular, renal impairment is common, has many causes, and carries with it
      increased morbidity and mortality. METHODS: We retrospectively analyzed clinical
      and laboratory data of 136 patients who underwent lung and heart-lung
      transplantation at our institution between 1990 and 2004 inclusive. Using
      multivariate analysis we considered the impact of age, gender, pulmonary
      diagnosis, transplant type (single lung, double lung, heart-lung), hypertension,
      diabetes mellitus, cigarette smoking, current immunosuppression, duration of
      calcineurin inhibitor (CNI) exposure and pre-existing renal impairment on renal
      function. RESULTS: At transplantation, creatinine clearance (CrCl) for the
      patient population was 108 +/- 3.28 (mean +/- SEM) ml/min/1.73 m(2). At end of
      follow-up (6 +/- 0.32 years) there was a significant decline in glomerular
      filtration rate (GFR) to 56.7 +/- 1.78 ml/min/1.73 m(2) (p < 0.001). Five of 136
      patients (3.7%) developed end-stage renal failure (ESRF). On multivariate
      analysis, factors most strongly associated with this decline included (in order
      of significance): CrCl at transplantation; pack-years of cigarette smoking;
      exposure to sirolimus (SLM); CNI exposure; and age at transplantation. The rate
      of decline in GFR was linked to CrCl and age at the time of transplantation.
      CONCLUSIONS: This analysis has demonstrated that patients with a lower baseline
      CrCl, older age at transplantation, and a smoking history are at high risk for
      rapid loss of renal function after transplantation. To best preserve kidney
      function, these patients should be targeted for aggressive risk factor
      modification as well as minimization of CNI exposure wherever possible.

PMID- 17178339
TI  - Assessment of adenovirus infection in adult lung transplant recipients using
      molecular surveillance.
AB  - BACKGROUND: Little is known about adenovirus infections in adult lung transplant
      recipients. Because the virus can establish latency, re-activation may be
      relatively common after transplantation. METHODS: We assessed adenovirus
      infection in 80 adult lung transplant recipients. Adenovirus polymerase chain
      reaction (real-time PCR assay; limit of detection approximately 25 copies/ml
      plasma) was done on plasma samples collected at regular intervals until 1 year
      post-transplant. RESULTS: Adenovirus DNA was detected in 18 of 80 patients
      (22.5%) and in 19 of 595 (3.4%) plasma samples up to 12 months post-transplant.
      Median time to detection of viremia was 134 days post-transplant (range 1 to 370
      days). Median viral load was 180 copies/ml plasma (range 50 to 360 copies/ml).
      Symptoms were evaluated at the time of adenovirus detection: 14 of 18 (78%)
      patients were asymptomatic; 4 of 18 (22%) patients had otherwise unexplained
      febrile/flu-like illness that resolved spontaneously. Adenovirus was not found to
      be a trigger for acute rejection. No detrimental effect on pulmonary function was
      seen immediately after adenovirus infection. CONCLUSIONS: Adenovirus viremia is
      common in adult lung transplant recipients. In contrast to findings on adenoviral
      pneumonitis in lung transplant recipients, isolated episodes of low-level viremia
      are self-limited and do not trigger acute rejection or a decline in pulmonary
      function.

PMID- 17178338
TI  - The phosphodiesterase type IV inhibitor cilomilast decreases pro-inflammatory
      cytokine production from primary bronchial epithelial cells in lung
      transplantation patients.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) remains the major cause of
      long-term morbidity and mortality after lung transplantation, and new therapeutic
      measures are needed. We speculated that cilomilast might reduce mediators of
      airway inflammation and angiogenesis from the airway epithelium, supporting a
      potential value in the treatment of BOS. We used an ex vivo primary bronchial
      epithelial cell culture (PBEC) model to investigate this hypothesis. Increasing
      evidence suggests the epithelium is central in stimulating both inflammatory and
      proliferative responses in the airway. METHODS: Bronchial brushings were taken
      from 7 stable lung allograft recipients and were used to establish sub-confluent
      PBECs. The effect of incubation for 48 hours with 0.1 to 10 micromol/liter
      cilomilast on basal production of interleukin (IL)-8, IL-6, granulocyte
      macrophage colony-stimulating factor (GMCSF), and vascular endothelial growth
      factor (VEGF) were assayed by multiplex analyser. RESULTS: There was a dose
      dependent fall in basal IL-8 and GMCSF levels with cilomilast. Median change for
      IL-8 was -25% (range, -66% to 5%; p = 0.035) at 1 micromol/liter , and -40%
      (range, -72% to -20; p = 0.022) at 10 micromol/liter. Median GMSCF change was 
      34% (range, -70% to 16%; p = 0.05) at 1 micromol/liter, and 37% (range, -80% to 
      8%; p = 0.04) at 10 micromol/liter. There were no effects on VEGF. CONCLUSION:
      The phosphodiesterase type IV inhibitor cilomilast reduced IL-8 and GMCSF release
      from PBECs. These cytokines are associated with the persistence of airway
      neutrophilic inflammation and airway remodelling seen in obliterative
      bronchiolitis. These ex vivo results suggest a potential for cilomilast in the
      treatment of BOS, which would need to be evaluated in appropriate clinical
      studies.

PMID- 17178340
TI  - Mycobacterium abscessus infections in lung transplant recipients: the
      international experience.
AB  - BACKGROUND: The clinical significance of Mycobacterium abscessus infection in the
      lung transplant population is not well understood. METHODS: An international
      survey was performed to determine the incidence and clinical outcomes of M
      abscessus infections before and after lung transplantation. RESULTS: Thirty-one
      (50%) of the 62 transplant centers affiliated with the International Society of
      Heart and Lung Transplantation responded to the survey. Of 5,200 transplants
      performed, 17 patients (0.33%) (M/F, 12:5) were identified with M abscessus after
      transplantation. Two patients had respiratory colonization before lung
      transplantation. Post-transplantation M abscessus infections occurred in the
      pulmonary allograft in 12, in skin/soft tissue in 3, or both in 2. Median time to
      diagnosis after transplantation was 18.5 months (range, 1-111 months). Therapies
      included multiple antibiotics in 16, surgical debridement in 2, interferon-gamma
      in 1, or no therapy owing to presumed colonization in 1. Eleven (73%) of 16
      treated patients had a radiologic or microbiologic response to treatment.
      Concurrent infections were common, with Aspergillus (n = 8) and Pseudomonas
      aeruginosa (n = 5) most frequently seen. Death in 2 patients was attributed to M
      abscessus. Ten of 17 patients are alive and considered cured. CONCLUSIONS: M
      abscessus infection in the lung transplant recipient is uncommon and challenging;
      however, successful treatment can occur. Prolonged combination anti-microbial
      therapy is required for pulmonary involvement, and surgical debridement is
      recommended for cutaneous lesions. Concurrent infections are common and may
      contribute to mortality in this immunosuppressed population.

PMID- 17178341
TI  - Intravascular ultrasound evidence of angiographically silent allograft
      vasculopathy inversely correlates with circulating level of hepatocyte growth
      factor.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is the major determinant of long
      term survival after heart transplantation. The characteristic diffuse concentric
      intimal thickening of CAV detected by intravascular ultrasound (IVUS) imaging may
      not be perceivable on coronary angiogram. Previous studies of hepatocyte growth
      factor (HGF) in murine models suggested the protective effects on vascular
      endothelium and allograft survival. However, the possible role of circulating HGF
      that contributes to the development of CAV in human is unclear. METHODS: IVUS was
      used to assess the left anterior descending coronary arteries of 47 patients who
      had survived cardiac transplantation for more than 1 year and had no
      angiographically detectable CAV. The IVUS measurements for the extent of intimal
      hyperplasia, including volume index (calculated as [total plaque volume/total
      vessel volume] x 100) and maximum area stenosis, were compared with plasma levels
      of HGF by linear regression analyses. RESULTS: The volume index significantly
      correlated with maximum area stenosis in the IVUS measurements (r = 0.90, p <
      0.0001). Both volume index and maximum area stenosis inversely correlated with
      plasma HGF levels (r = -0.39, p = 0.007 and r = -0.42, p = 0.003, respectively).
      CONCLUSIONS: In angiographically silent CAV, circulating HGF may have a
      protective effect on vascular endothelium and thus attenuate the severity of
      intimal hyperplasia.

PMID- 17178343
TI  - Attenuation of lung reperfusion injury by modified ventilation and reperfusion
      techniques.
AB  - BACKGROUND: High ventilation and perfusion pressures after lung transplantation
      may have deleterious effects. We hypothesized that using combined protective
      approaches for ventilation and perfusion would be optimal for reducing injury and
      improving function after ischemia-reperfusion. METHODS: Using an isolated, blood
      perfused, rabbit lung model, lungs underwent 120 minutes of reperfusion either
      immediately (Sham) or after 18 hours of cold ischemia (IR). Groups Sham-P and IR
      P underwent protective ventilation and reperfusion, and Groups Sham-C and IR-C
      underwent conventional ventilation and reperfusion. Protective ventilation
      involved gradually increasing the flow rate during 5 minutes to 1.8 liters/min,
      and conventional ventilation entailed immediate initiation of flow at 1.8
      liters/min. Protective reperfusion involved gradually increasing perfusion during
      5 minutes to 60 ml/min, and conventional reperfusion entailed immediate perfusion
      at 60 ml/min. Two other groups underwent either protective ventilation with
      conventional perfusion or vice versa. Airway pressure, pulmonary artery pressure,
      and arterial blood gases were measured throughout reperfusion. Wet/dry weight,
      highest oxygenation index, and bronchoalveolar lavage (BAL) protein were also
      measured. RESULTS: Protective ventilation and perfusion after ischemia (IR-P)
      resulted in significant improvements in lung function as measured by increased
      Po(2) and decreased Pco(2), airway pressure, and highest oxygenation index
      compared with conventional reperfusion (IR-C). Injury was significantly reduced
      in IR-P lungs as measured by reduced edema (wet/dry weight) and vascular leakage
      (BAL protein). In most cases, IR-P lungs performed better, with less injury than
      protective ventilation or perfusion alone. CONCLUSIONS: This protective approach
      of ventilation and perfusion after ischemia may improve lung function after
      transplantation, a simple method that could easily be applied clinically.

PMID- 17178342
TI  - Rituximab as monotherapy for elicited xenoreactive antibody responses.
AB  - PURPOSE: This study was conducted in a non-human primate model to determine the
      impact of the rituximab, an anti-CD20 monoclonal antibody, as monotherapy on
      elicited xenoreactive antibody responses. METHODS: Adult baboons were divided
      into 2 groups: Group 1 baboons were treated with rituximab then sensitized with
      porcine red blood cells; Group 2 baboons did not receive rituximab but were
      immunized with porcine red blood cells. Both groups were followed-up
      prospectively for 4 weeks. During this time, sera and peripheral lymphocytes were
      collected for analysis. Anti-galactose-alpha (Galalpha)-1-3 Gal-immunoglobulin
      (Ig) M and anti-IgG antibody titers were measured using porcine cell enzyme
      linked immunosorbent assay, and flow-cytometry was used to study populations of B
      cells after rituximab therapy. RESULTS: After the administration of rituximab,
      baboons in Group 1 had a detectable decrease in the percent of CD19(+)/CD20(+) B
      cells. The effect of rituximab lasted for more than a month in this group.
      Despite the elimination of B cells, both groups developed vigorous anti-Galalpha
      1-3 Gal antibody responses, which were evident within 12 days of immunizations.
      Furthermore, this increase in the anti-Galalpha-1-3 Gal antibody titers was
      accompanied by a relative rise in the percentage of double negative (CD19(
      )/CD20(-)) but IgM(+) and IgG(+) B cells. CONCLUSIONS: In a non-human primate
      model of xenotransplantation, anti-Galalpha-1-3 Gal antibody responses were
      elicited despite the elimination of B cells by rituximab. These responses seem to
      be mediated in part by cells lacking common B-cell surface antigens.

PMID- 17178344
TI  - Prolonged amelioration of acute lung allograft rejection by overexpression of
      human interleukin-10 under control of a long acting ubiquitin C promoter in rats.
AB  - BACKGROUND: The prolonged effect of electroporation-mediated human interleukin-10
      (hIL-10) overexpression in skeletal muscle under the control of the
      constitutional polyubiquitin C promoter (pUb hIL-10) on rat lung allograft
      rejection was evaluated. METHODS: Left lung allotransplantation was performed
      from Brown-Norway to Fischer-F344 rats. Either 2.5 mug pCIK hIL-10 (hIL
      10/cytomegalovirus early promoter enhancer) alone (Group I/sacrifice Day 5 and
      II/sacrifice Day 10) or in combination with 2.5 mug pUb hIL-10 (hIL-10/UbC
      promoter; Group III/sacrifice Day 10) were injected into the tibialis anterior
      muscle of the recipient, followed by electroporation 24 hours before
      transplantation. Animals in Control Groups IV and V without gene transfer were
      euthanized on Day 5 and 10, respectively. All animals received a daily non
      therapeutic dose of cyclosporine A (2.5 mg/kg). RESULTS: In Control Group IV,
      complete rejection (median A3B3) was noted on Day 5 with a Pao(2) of 43 +/- 9 mm
      Hg. In recipients of Control Group V, measurement of gas exchange on Day 10 and
      rejection grading was impossible because of complete destruction of the
      allograft. Group I animals on Day 5 (233 +/- 123 mm Hg; p = 0.02 vs Group IV) and
      Group II animals on Day 10 (150 +/- 139 mm Hg; p = 0.15 vs Group IV) demonstrated
      improved graft function. Graft function in Group III was further improved on Day
      10 (299 +/- 123 mm Hg; p = 0.002 vs Group IV; p = 0.05 vs Group II; p = 0.36 vs
      Group I). Rejection was significantly reduced in Group III (median, A2B2)
      compared with Group II (median, A4B3; p < 0.05). CONCLUSIONS: Interleukin-10
      overexpression under control of the constitutive ubiquitin C promoter ameliorates
      acute rejection and preserves lung graft function for a prolonged time.

PMID- 17178345
TI  - Mechanical circulatory support as a bridge to combined dual organ transplantation
      in children.
AB  - The use of mechanical circulatory support as a bridge to cardiac transplantation
      is now an accepted therapeutic option. Also, as the criteria for organ
      transplantation have broadened, multi-organ transplantation has become more
      feasible. We report the cases of 2 children with end-stage heart failure and
      renal failure who were successfully bridged to combined, single-donor heart and
      kidney transplantation with mechanical circulatory support.

PMID- 17178346
TI  - Non-invasive ventilation in phrenic nerve dysfunction after lung transplantation:
      an attractive option.

PMID- 17178347
TI  - Absolute parameters or mathematical models for the timing of cardiac
      transplantation.

PMID- 17178348
TI  - Changes in matrix metalloproteinase 2 activities in amniochorions during
      premature rupture of membranes.
AB  - OBJECTIVE: Increased proteolytic activities of matrix metalloproteinases (MMPs)
      such as MMP-3 and MMP-9 are associated with premature rupture of membranes at
      term. However, it is unclear whether MMP-2 is involved in the premature rupture
      of membranes. In this study, to elucidate the role of MMP-2, we evaluated the
      activity of MMP-2 and also the expression of pro-MMP-2, membrane type 1 (MT1)-MMP
      and tissue inhibitor of metalloproteinase (TIMP)-1 in premature rupture of
      membranes. METHODS: Amniochorions were prepared from 29 subjects with no labor
      (cesarean section; CS, n = 10), labor (normal delivery; ND, n = 10), and labor
      during premature rupture of membranes (PROM, n = 9). MMP-2 activity was
      spectrophotometrically assayed by measuring the digestion of an MMP-2-specific
      substrate. The levels of pro-MMP-2, MT1-MMP and TIMP-1 were determined by Western
      immunoblotting. RESULTS: The activity of MMP-2 in PROM was significantly higher
      than that in CS and ND (P <.05). In addition, the levels of MT1-MMP, an activator
      of MMP-2, were higher in PROM than in CS and ND. In contrast, the level of TIMP
      1, an inhibitor of MMP-2 was substantially lower in PROM than CS and ND.
      Moreover, the levels of pro-MMP-2 were increased more significantly in PROM and
      ND than in CS (P <.05). CONCLUSION: Our results suggest that the increased
      expression of pro-MMP-2 and MT1-MMP and decreased expression of TIMP-1 may result
      in the increased activity of MMP-2, which is involved in the degradation of
      extracellular matrix (ECM) of fetal membrane, thereby inducing the premature
      rupture of membranes at term.

PMID- 17178350
TI  - The office management of epilepsy.
AB  - Epilepsy in children is mostly diagnosed and treated in an ambulatory office
      setting. This article reviews the literature and offers opinions about the best
      practice from the time of diagnosis through to remission and beyond. The
      diagnosis and assignment of an epilepsy syndrome may be difficult, and even
      experts disagree in many cases. Regular review of the basic diagnosis and
      semiology of seizures is suggested throughout treatment. Workup should always
      include an electroencephalogram and usually magnetic resonance imaging.
      Antiepileptic drugs (AEDs) suppress seizures but appear to have little effect on
      long-term remission, and the choice of AED is for the most part arbitrary with
      most AEDs having a similar success rate when used as the first drug. Families
      have a great need for accurate information, and their ability to cope with the
      unpredictable nature of seizures may be assisted by "rescue" home
      benzodiazepines. Surveillance for drug toxicity and side effects is a critical
      clinical skill that is not assisted by routine blood tests or AED serum levels.
      Most children with epilepsy do not have many seizures and need not have
      significant restrictions on their activities. In the long run, comorbidities
      (especially learning and behavior problems) have a greater impact on social
      function than the epilepsy. Management of these problems may extend well beyond
      remission of the epilepsy. The child neurologist needs to prepare children with
      persistent epilepsy for transfer to adult epilepsy services.

PMID- 17178351
TI  - Paroxysmal nonepileptic events of childhood.
AB  - The paroxysmal nonepileptic events of childhood are a group of disorders,
      syndromes, and phenomena that mimic true epileptic seizures. Clinical experience
      and a clear description of the event in question will usually lead to a correct
      categorization. They span in age from neonate to young adult and are apt to be
      the most common diagnostic challenges clinicians face regularly. The key to
      diagnosis is a detailed history and careful observation. Despite the large number
      of discrete entities enumerated herein, common principles in clinical approach
      are successful and described. Each entity can pose a significant clinical
      challenge in identification, etiologic pathophysiology, genetics, and management.
      A simple division is offered here separating those episodes that are associated
      with an altered mental status or occurring during sleep and those without an
      altered mental status or occurring while awake.

PMID- 17178352
TI  - Headaches in the pediatric population.
AB  - Headaches are an extremely common complaint encountered in the pediatric
      population. The headache history establishes the diagnosis in the vast majority
      and most importantly identifies features suggesting a secondary cause. The
      headache history outlined will aid in headache classification and screen for
      ominous causes. A comprehensive headache examination is aimed at excluding
      secondary causes. Headaches resulting from serious organic causes are virtually
      always associated with neurologic signs at the time of presentation.
      Investigations are not routinely required for pediatric headache, but
      neuroimaging should be strongly considered in children with an abnormal
      neurologic examination or history worrisome for intracranial pathology. The
      management approach for children with primary headaches should focus on
      reassurance and education. Developing an individualized therapeutic strategy
      requires knowledge of the child's headache-related disability and impact on
      quality of life. Treatment should begin with a nonpharmacologic approach, which
      influences lifelong prevention and management of headaches. Pharmacologic
      interventions target both acute symptomatic treatment and prophylactic
      medications. Preventative treatment may be beneficial when headaches result in
      significant disability and impaired quality of life. The limited available
      evidence for prophylactic treatment options is reviewed. Research into pediatric
      headache prevention and management remains a priority given the potential
      lifelong morbidity associated with headache.

PMID- 17178353
TI  - Tic disorders in childhood.
AB  - Despite our familiarity with tic disorders, their management remains challenging.
      The difficulty seldom relates to the diagnosis, which is usually based on the
      history, but rather in dealing with the impact of the tics and multiple
      comorbidities. The child and family must be educated and must be taught how to
      facilitate a positive attitude among others who come in contact with the patient.
      Knowledge and acceptance of the tics by other family members, peers, teachers,
      and coaches often become central to the child's well-being. Although many
      children can be managed without pharmacotherapy, medications are often central to
      achieving success. The goals of therapy and the appropriate choice of medication
      must be individualized. We are frequently challenged not only by the wide array
      of medication choices available but also by the decision of which symptom to
      treat first. The tics, despite being flamboyant, are often viewed by the child
      and family as less disabling than co-occurring conditions, such as attention
      deficit hyperactivity disorder, obsessive-compulsiveness, or rage. Even when tics
      are the major issue, patients must define their goals for therapy. It is
      unreasonable to expect a complete resolution of tics and safety usually rules in
      favor of better tolerated but potentially less efficacious therapies. Developing
      strategies to minimize the lifelong impact of the multiple components of Tourette
      syndrome is an essential aspect of the care of these patients.

PMID- 17178354
TI  - Pediatric minor traumatic brain injury.
AB  - The literature surrounding minor traumatic brain injury is complex,
      methodologically challenging, and controversial. Although we lack a consistent
      standardized definition, the annual rate is likely in excess of 200 per 100,000
      children. The proportion of children with minor traumatic brain injury who will
      require neurosurgery is certainly <1%. Several studies are underway that have the
      potential to significantly advance our understanding of the specific risk factors
      for intracranial injury and more specifically neurosurgical injury. The mortality
      within children is very low, with estimates of 0% to 0.25%. Virtually all studies
      of the prognosis of minor brain injury in children have reported no long-term
      behavioral or cognitive sequelae as a specific result of the brain injury.
      Symptoms fall in 4 domains: somatic, cognitive, sleep/fatigue, and affective.
      Limited pediatric studies are available to assist clinicians in the prognosis or
      in optimizing recovery. Until further studies are available, a conservative
      approach is recommended. Children with suspected concussions should be removed
      from activity and observed. Children with symptomatic concussions must be limited
      to no physical activity. Adolescents and families need to self-monitor symptoms
      and limit environments or circumstances that exacerbate any symptoms. When
      symptoms resolve, a gradual progressive return to play is currently recommended.
      The recurrence risk for subsequent concussions is elevated, but there is limited
      documentation of the effectiveness of preventative efforts. Much remains to be
      learned.

PMID- 17178355
TI  - Office evaluation of the child with developmental delay.
AB  - Developmental delays are a common problem in child health and a frequent reason
      for referral to a pediatric subspecialist. The office evaluation of the young
      delayed child has a number of objectives including primarily precisely
      categorizing the delay subtype together with rationally selecting investigations
      for determining a possible underlying etiology. Counseling the affected family
      regarding the diagnosis and its prognosis, identifying possible coexisting
      conditions that merit interventions, and ensuring appropriate rehabilitation
      service provision are also important objectives of this office assessment. An
      outline of the key features of the relevant history and physical examination
      together with guidelines regarding investigations are provided to best meet all
      these objectives within existing time and practice constraints.

PMID- 17178356
TI  - Mental retardation in children ages 6 to 16.
AB  - Mental retardation (MR) is a life long condition that affects 6 million American
      and 560,000 Canadian children under the age of 14. This review discusses the
      definition of MR, an approach to investigation, common comorbidities, and a
      general approach to management.

PMID- 17178357
TI  - Management of the child with weakness.
AB  - With increased life expectancy associated with improved respiratory care and
      research advances in pediatric neuromuscular diseases leading to clinical trials
      involving potential curative treatments, the goal in the care of the child with
      weakness is to optimize survival and quality of life. The care of the child with
      weakness includes management of motor dysfunction because of weakness, orthopedic
      complications of contractures and scoliosis, and comorbid complications specific
      to each neuromuscular disease. Optimal holistic integrative care of the
      multisystemic problems of such patients is best provided by the collaborative
      efforts of health care providers of an interdisciplinary team.

PMID- 17178358
TI  - Attention-deficit hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a challenging condition to
      diagnose and treat. For diagnosis, the clinician needs to establish the presence
      of ADHD on Diagnostic and Statistical Manual of Mental Disorders criteria
      requiring information from parents and teachers and considering both alternative
      diagnoses and co-occurring conditions. In the treatment of ADHD as a chronic
      illness, the clinician needs to educate the family about the condition and
      partner with them about treatment decisions. The 2 treatments with demonstrated
      efficacy for ADHD are medications (stimulant medications and a selective
      norepinephrine reuptake inhibiter) and behavior-modification programs.

PMID- 17178359
TI  - The child with cerebral palsy: diagnosis and beyond.
AB  - Cerebral palsy (CP) is one of the most common conditions we follow in our
      pediatric neurology offices. This review will hopefully convince you that the
      care of children with CP extends far beyond the diagnosis. The review addresses
      issues surrounding diagnosis, coimpairments, prognosis, and family-centeredness
      of care. It will also deal with routine office follow-up to prevent or identify
      complications, management of spasticity and other morbidities, alternative and
      complementary therapies, and finally transition.

PMID- 17178360
TI  - Expense reduction through distance learning.

PMID- 17178361
TI  - Spatial localization accuracy of radiologists in free-response studies: Inferring
      perceptual FROC curves from mark-rating data.
AB  - RATIONALE AND OBJECTIVES: Free-response data consist of a set of mark-ratings
      pairs. Before analysis, the data are classified or "scored" into lesion and non
      lesion localizations. The scoring is done by choosing an acceptance-radius and
      classifying marks within the acceptance-radius of lesion centers as lesion
      localizations, and all other marks are classified as non-lesion localizations.
      The scored data are plotted as a free-response receiver operating characteristic
      (FROC) curve, essentially a plot of appropriately normalized numbers of lesion
      localizations vs. non-lesion localizations. Scored FROC curves are frequently
      used to compare imaging systems and computer-aided detection (CAD) algorithms.
      However, the choice of acceptance-radius is arbitrary. This makes it difficult to
      compare curves from different studies and to estimate true performance. MATERIALS
      AND METHODS: To resolve this issue the concept of two types of marks is
      introduced: perceptual hits and perceptual misses. A perceptual hit is a mark
      made in response to the observer seeing the lesion. A perceptual miss is a mark
      made in response to the observer seeing a (lesion-like) non-lesion. A method of
      estimating the most probable numbers of perceptual hits and misses is described.
      This allows one to plot a perceptual FROC operating point and by extension a
      perceptual FROC curve. Unlike a scored FROC operating point, a perceptual point
      is independent of the choice of acceptance-radius. The method does not allow one
      to identify individual marks as perceptual hits or misses-only the most probable
      numbers. It is based on a three-parameter statistical model of the spatial
      distributions of perceptual hits and misses relative to lesion centers. RESULTS:
      The method has been applied to an observer dataset in which mammographers and
      residents with different levels of experience were asked to locate lesions in
      mammograms. The perceptual operating points suggest superior performance for the
      mammographers and equivalent performance for residents in the first and second
      mammography rotations. These results and the model validation are preliminary as
      they are based on a small dataset. CONCLUSION: The significance of this study is
      showing that it is possible to probabilistically determine if a mark resulted
      from seeing a lesion or a non-lesion. Using the method developed in this study
      one could perform acceptance-radius independent estimation of observer
      performance.

PMID- 17178362
TI  - Acute abdomen: Added diagnostic value of coronal reformations with 64-slice
      multidetector row computed tomography.
AB  - RATIONALE AND OBJECTIVES: We sought to assess retrospectively the added value of
      coronal reformations from isotropic voxels obtained with 64-slice multidetector
      row computed tomography (CT) of the acute abdomen. MATERIALS AND METHODS: This
      retrospective study was approved by the institutional review board and informed
      consent was waived. Multidetector helical 64-section CT (section thickness, 0.6
      mm; pitch 1.75; table speed 35 mm/sec) was performed in 100 patients (60 women
      and 40 men; age range, 9-/+85 years; mean age, 45.2 years) with acute
      nontraumatic abdominal pain who had been referred from the emergency department.
      Axial images were reconstructed with 5-mm-thick sections at 5-mm intervals. The
      second data set was reformatted coronally, with 3-mm-thick sections at 3-mm
      intervals. Four independent, blinded readers with various level of training
      interpreted first the axial scans alone and then followed immediately by the
      coronal scans. Confidence in the visualization of anatomy and pathology was
      scored on a 5-point scale. The final diagnosis was determined by surgical and
      pathologic reports and by clinical follow-up in those who did not undergo
      surgery. RESULTS: Based upon the individual patient's clinical history and other
      comorbid factors, 92 patients received intravenous contrast and 90 patients
      received oral contrast. In 45 patients, no CT abnormalities were detected for an
      explanation of the abdominal pain. Mean sensitivity and specificity of axial CT
      alone were 92.5% and 91%, respectively. No significant differences in sensitivity
      and specificity were observed for the use of combined axial and coronal images.
      For the most inexperienced reader, the coronal reformations were helpful in 95%
      of cases, while for the most experienced reader, the coronal reformations were
      helpful in 35% of the cases. The coronal images were deemed helpful in an average
      of 62.3% of the cases for the four readers. However, diagnosing subtle pathology
      in the abdominal wall was difficult on coronal reformations alone. Overall,
      coronal reformations improved diagnostic confidence and interobserver agreement
      over axial images alone for visualization of normal abdominal structures and in
      the diagnosis of abdominal pathology. CONCLUSION: Axial and coronal reformations
      of 64-section multidetector row CT have equal sensitivity and specificity for the
      diagnosis of acute abdominal pathology. However, coronal reformations improved
      the diagnostic confidence for all readers but most significantly for the least
      experienced. Therefore, radiology departments with residents should consider
      routinely generating coronal images in patients with acute abdominal pain.

PMID- 17178363
TI  - Computer-aided diagnosis for improved detection of lung nodules by use of
      posterior-anterior and lateral chest radiographs.
AB  - RATIONALE AND OBJECTIVES: We developed a computerized scheme for detection of
      lung nodules in the lateral views of chest radiographs, in order to improve the
      overall performance in combination with the computer-aided diagnostic (CAD)
      scheme for posterior-anterior (PA) views. MATERIALS AND METHODS: We used 106
      pairs of PA and lateral views of chest radiographs (122 lung nodules) for
      development of the CAD scheme. In the CAD scheme for lateral views, initial
      candidates of lung nodules were identified by use of a nodule enhancement filter
      based on the edge gradients. Thirty-four image features extracted from the
      original and the nodule-enhanced images were used for the rule-based scheme and
      for artificial neural networks (ANNs) for removal of some false-positive
      candidates. The computer performance was evaluated with a leave-one-case-out test
      method for ANNs. For PA views, we used the existing CAD scheme, which was trained
      with one-half of 924 chest images and then tested with the remaining images.
      RESULTS: When the CAD scheme was applied only to PA views, the sensitivity in the
      detection of lung nodules was 70.5%, with 4.9 false positives per image. Although
      the performance of the computerized scheme for lateral views was relatively low
      (60.7% sensitivity with 1.7 false positives per image), the overall sensitivity
      (86.9%) was improved (6.6 false positives per two views), because 20 (16.4%) of
      the 122 nodules were detected only on lateral views. CONCLUSIONS: The CAD scheme
      by use of lateral-view images has the potential to improve the overall
      performance for detection of lung nodules on chest radiographs when combined with
      a conventional CAD scheme for standard PA views.

PMID- 17178365
TI  - The prevalence effect in a laboratory environment: Changing the confidence
      ratings.
AB  - RATIONALE AND OBJECTIVES: We sought to assess whether or not prevalence levels
      affected the confidence ratings of readers during the interpretation of cases in
      a laboratory receiver operating characteristic-type observer performance study.
      MATERIALS AND METHODS: We reanalyzed a previously conducted observer performance
      study that included 14 readers and 5 different levels of prevalence. The previous
      study yielded the observation that in the laboratory we could not detect a
      "prevalence effect" in terms of differences in areas under the receiver operating
      characteristic curves. The detection ratings (for presence or absence) of lung
      nodules, interstitial disease, and pneumothorax for the five prevalence levels
      were compared, and a test for trend in averaged ratings as a function of
      abnormality prevalence was performed within a mixed-model setting that accounts
      for different sources of variability and correlations induced by the study
      design. RESULTS: The ratings of the cases in terms of confidence that the
      specific abnormality in question is present tend, on average, to be larger when
      actual disease prevalence is lower. The rate of the increase of the average
      confidence ratings with the decreasing prevalence of a specific abnormality is
      very similar for actually positive and actually negative cases for every
      considered abnormality. The observed trend in the changes of the average
      confidence ratings as a function of prevalence levels was statistically
      significant (p < 0.01). CONCLUSION: Expectations of disease prevalence in the
      case mix during a laboratory observer performance study may systematically affect
      the behavior of observers in terms of their actual confidence ratings.

PMID- 17178364
TI  - Quasi-continuous and discrete confidence rating scales for observer performance
      studies: Effects on ROC analysis.
AB  - RATIONALE AND OBJECTIVES: To examine the effects of the number of categories in
      the rating scale used in an observer experiment on the results of ROC analysis by
      a simulation study. MATERIALS AND METHODS: We have previously evaluated the
      effects of computer-aided diagnosis on radiologists' characterization of
      malignant and benign breast masses in serial mammograms. The evaluation of the
      likelihood of malignancy was performed on a quasi-continuous (0-100 points)
      confidence rating scale. In this study, we simulated the use of discrete
      confidence rating scales with fewer number of categories and analyzed the results
      with receiver operating characteristic (ROC) methodology. The observers'
      estimates of the likelihood of malignancy were also mapped to BI-RADS assessments
      with five and seven categories and ROC analysis was performed. The area under the
      ROC curve and the partial area index obtained from ROC analysis of the different
      confidence rating scales were compared. RESULTS: The fitted ROC curves and the
      performance indices do not change significantly when the confidence rating scales
      were varied from 6 to 101 points if the estimated operating points obtained
      directly from the data are distributed relatively evenly over the entire range of
      true-positive fraction (TPF) and false-positive fraction (FPF). The mapping of
      the likelihood of malignancy observer data to the seven-category BI-RADS
      assessment scale allowed reliable ROC analysis, whereas mapping to the five
      category BI-RADS scale could cause erratic ROC curve fitting because of the lack
      of operating points in the mid-range or failure in ROC curve fitting because of
      data degeneration for some observers. CONCLUSION: ROC analysis of discrete
      confidence rating scales with few but relatively evenly distributed data points
      over the entire FPF and TPF range is comparable to that of a quasi-continuous
      rating scale. However, ROC analysis of discrete confidence rating scales with few
      and unevenly distributed data points may cause unreliable estimations.

PMID- 17178366
TI  - Optimization of spatial resolution for peripheral magnetic resonance angiography.
AB  - RATIONALE AND OBJECTIVES: To determine optimum spatial resolution when imaging
      peripheral arteries with magnetic resonance angiography (MRA). MATERIALS AND
      METHODS: Eight vessel diameters ranging from 1.0 to 8.0 mm were simulated in a
      vascular phantom. A total of 40 three-dimensional flash MRA sequences were
      acquired with incremental variations of fields of view, matrix size, and slice
      thickness. The accurately known eight diameters were combined pairwise to
      generate 22 "exact" degrees of stenosis ranging from 42% to 87%. Then, the
      diameters were measured in the MRA images by three independent observers and with
      quantitative angiography (QA) software and used to compute the degrees of
      stenosis corresponding to the 22 "exact" ones. The accuracy and reproducibility
      of vessel diameter measurements and stenosis calculations were assessed for
      vessel size ranging from 6 to 8 mm (iliac artery), 4 to 5 mm (femoro-popliteal
      arteries), and 1 to 3 mm (infrapopliteal arteries). Maximum pixel dimension and
      slice thickness to obtain a mean error in stenosis evaluation of less than 10%
      were determined by linear regression analysis. RESULTS: Mean errors on stenosis
      quantification were 8.8% +/- 6.3% for 6- to 8-mm vessels, 15.5% +/- 8.2% for 4-
      to 5-mm vessels, and 18.9% +/- 7.5% for 1- to 3-mm vessels. Mean errors on
      stenosis calculation were 12.3% +/- 8.2% for observers and 11.4% +/- 15.1% for QA
      software (P = .0342). To evaluate stenosis with a mean error of less than 10%,
      maximum pixel surface, the pixel size in the phase direction, and the slice
      thickness should be less than 1.56 mm2, 1.34 mm, 1.70 mm, respectively (voxel
      size 2.65 mm3) for 6- to 8-mm vessels; 1.31 mm2, 1.10 mm, 1.34 mm (voxel size
      1.76 mm3), for 4- to 5-mm vessels; and 1.17 mm2, 0.90 mm, 0.9 mm (voxel size 1.05
      mm3) for 1- to 3-mm vessels. CONCLUSION: Higher spatial resolution than currently
      used should be selected for imaging peripheral vessels.

PMID- 17178367
TI  - Cranial CT for diagnosis of intracranial complications in adult and pediatric
      patients during ECMO: Clinical benefits in diagnosis and treatment.
AB  - RATIONALE AND OBJECTIVES: To evaluate the clinical utility of cranial computed
      tomography (CT) in pediatric and adult patients during ongoing extracorporeal
      membrane oxygenation (ECMO) treatment from acute respiratory failure and to
      assess the frequency of intracranial hemorrhage (ICH) and infarction during the
      treatment. MATERIALS AND METHODS: The medical records of 123 consecutive
      patients, 54 children (ages 3 months-17 years) and 69 adults (ages 18-62 years),
      treated with ECMO over a 10-year period were searched for cranial CT performed
      during ECMO. Indications for CT, CT findings, impact on clinical management, and
      patient outcome were noted. In addition, all CT scans were reviewed for the
      frequency of ICH or infarction. RESULTS: Seventy-eight patients had cranial CT
      while on ECMO. ICH or cerebral infarction were detected in 45 (37%) of the 123
      patients. Eighteen patients (15%) had focal hemorrhage, 11 (9%) focal infarction,
      and 16 (13%) general brain edema. In 16 of the 45 patients, the CT findings were
      decisive to withdraw the ECMO treatment. Five patients were weaned from ECMO, and
      in four patients the findings motivated cranial surgery during ECMO. In the
      remaining 20 patients with less extended intracranial pathology, the ECMO
      treatment was continued with high survival. CONCLUSION: Cranial CT has an
      important role during ECMO treatment to reveal or exclude severe intracranial
      complications where ECMO treatment should be discontinued. Less severe
      complications have a favorable prognosis with continued treatment. Our study
      suggests an underreporting of intracranial complications in adults and pediatric
      patients on ECMO because of low utilization of neuroimaging.

PMID- 17178368
TI  - Revisiting oral barium sulfate contrast agents.
AB  - Oral contrast agents used during CT colonography (CTC) are valuable and may
      reduce false positive and false negative detections due to stool and residual
      fluid. Electronic cleansing algorithms are feasible, and oral contrast agents can
      eliminate the CTC requirement for a clean colon. Recent work shows oral contrast
      frequently adheres to polyps, with a preference for those with villous histology,
      a characteristic of advanced polyps. This finding encourages the development of
      contrast agents that highlight polyps at greatest risk for progression to
      malignancy. Our review summarizes numerous aspects of oral barium sulfate
      contrast agents as well as tests to assess adherence and coating ability of the
      agents, offering arenas to explore and tools for evaluation.

PMID- 17178370
TI  - Local toxicity of hepatic arterial infusion of hexokinase II inhibitor, 3
      bromopyruvate: In vivo investigation in normal rabbit model.
AB  - RATIONALE AND OBJECTIVES: 3-Bromopyruvate (3-BrPA), an hexokinase II inhibitor,
      is known to have high necrotic rate in hyperglycolytic liver tumor models without
      apparent damage to the normal liver parenchyma. The toxicity of intra-arterial
      delivery of 3-BrPA in various concentrations has not been specifically
      investigated using a normal rabbit model. MATERIALS AND METHODS: Twenty rabbits
      treated with intra-arterial 3-BrPA were divided into four groups according to its
      dose and infusion level: 1 mM at the left hepatic artery (group I), 5 mM at the
      left hepatic artery (group II), 25 mM at the left hepatic artery (group III), and
      25 mM at the common hepatic artery (group IV). After selective catheterization,
      30 ml of 3-BrPA was infused for 2 minutes. As a control group, five rabbits were
      treated with normal saline. During 1-week follow-up, toxicities were evaluated
      with blood laboratory results, mortality, and histopathologic examination.
      RESULTS: All 10 rabbits treated with 25 mM 3-BrPA and 2 rabbits treated with 5 mM
      3-BrPA died within 3 days after treatment. In 10 of the 12 deaths, hemorrhagic
      pyloric or duodenal necrosis was noted. Hepatotoxicities on blood laboratory
      results were dose dependent but transient in the surviving rabbits. CONCLUSION:
      Selective intra-arterial administration of 25 mM 3-BrPA can cause considerable
      toxicities not only in the liver but also in the gastrointestinal system and are
      dose dependent and can cause death in high doses.

PMID- 17178369
TI  - Recirculation of inhaled xenon does not alter lung CT density.
AB  - RATIONALE AND OBJECTIVES: Xenon-enhanced computed tomography (Xe-CT) measures
      regional ventilation from changes in lung parenchymal CT density during the
      multibreath washin/washout of inhaled Xe gas. Because Xe is moderately soluble,
      vascular uptake and redistribution has been proposed as a confounding phenomenon.
      We propose that the redistribution of Xe via the circulation is negligible, and
      correction is unwarranted. MATERIALS AND METHODS: Unilateral ventilation with 60%
      Xe was performed in intubated canines. Whole-lung CT images were obtained at
      baseline and after 1 and 5 minutes of unilateral Xe ventilation. Comparisons
      between blocked (B) and Xe ventilated (V) whole lung densities were made. Density
      of paraspinous muscle and blood (aorta, inferior vena cava) were also compared.
      RESULTS: The density of lung tissue in the V lungs increased significantly
      compared to B lungs after 1 minute (B -688.5 +/- 54.3 Hounsfield units [HU] vs. V
      -535.4 +/- 55.6 HU, P < .05) and 5 minutes (B -689.1 +/- 52.2 HU vs. V -492.9 +/-
      89.1 HU, P < .05) of Xe ventilation. The density in the blocked lungs did not
      significantly change after either 1 or 5 minutes of ventilation with Xe. Although
      density tended to increase with time in the blood and muscle, the change only
      reached significance in muscle at 5 minutes. CONCLUSIONS: Five minutes of
      ventilation with a high concentration of Xe does not cause measurable density
      changes in the contralateral, unventilated lung. Xe accumulation in muscle tissue
      limits redistribution. Correction of Xe-CT time series density data may be
      unnecessary.

PMID- 17178371
TI  - Self-subsidization of educational expenses by senior radiology residents.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to document the degree of
      self-subsidization of educational expenses by senior radiology residents.
      MATERIALS AND METHODS: Questionnaires were distributed to all radiology residents
      (n = 176) attending the New Jersey Medical School board review course held twice
      in 2006. Respondents (n = 175) documented the number and source of financial
      support for review courses they had or would attend, including the AFIP course in
      radiologic pathology. They also listed the amount of additional financial
      allowances paid to them by their programs and cited the funding source for the
      radiology board examinations. RESULTS: Average AFIP expenditure, including
      tuition, room, board, and travel, equaled 3,969 dollars +/- 45 dollars, of which
      46% was paid by the residents themselves. The respondents attended, on average,
      two review courses costing 4,116 dollars +/- 149 dollars, bearing 77% of the
      costs. The average additional allowance paid to residents was 1,938 dollars +/-
      156 dollars. Total board expenditures of 3,120 dollars, including fees and
      travel, were borne entirely by the residents. Total out-of-pocket expenses for
      these activities was 7,928 dollars +/- 165 dollars, which amounted to 16% of
      senior residents' average annual salary (49,746 dollars). CONCLUSION: The desire
      by both programs and trainees for success on the radiology board examination has
      stimulated the growth of review courses. The enduring popularity of the AFIP
      course has made this activity an essential rotation for most radiology residency
      programs. Each of these off-site opportunities incurs significant financial
      obligations to residents, and when added to the cost of the board exams, equals
      16% of their average annual salary. Thus radiology residents are subsidizing
      their education to a considerable degree relative to their salaries. This study
      reveals that senior radiology residents significantly subsidize their education
      and bear the burden of hidden costs associated with their training.

PMID- 17178372
TI  - Problem-solving session results from the 54th Annual Meeting of the Association
      of University Radiologists.

PMID- 17178375
TI  - Amaurosis fugax secondary to imaging methods of MRI scan.

PMID- 17178377
TI  - Total flavonoids of Daphne genkwa root significantly inhibit the growth and
      metastasis of Lewis lung carcinoma in C57BL6 mice.
AB  - Daphne genkwa root has been traditionally used as an effective remedy to treat
      various tumors. However, the active constituents for its antitumor potency have
      not been well documented. During the screening for antitumor constituents, it was
      found that the total flavonoids of D. genkwa root (TFDR) were responsible for the
      inhibition of tumor growth and metastasis. In this study, TFDR was investigated
      for its chemical composition and activities against tumor growth and metastasis.
      HPLC indicates that daphnodorin B, containing 42.79% of the total, represents the
      predominant constituent in TFDR. Treatment of LLC-bearing mice with TFDR
      evidently protected peripheral lymphocytes from tumor-induced reduction, and
      increased lymphocyte proliferation potential and cytolytic activity of NK, and
      inhibited tumor progression and metastasis either 7 days before, or simultaneous
      with, or 7 days after LLC transplantation. TFDR also suggested higher
      cytotoxicity to a number of tumor cell lines than that to normal human kidney
      cell K293. TFDR also induced an enhancement on peripheral release of TNF-alpha at
      doses between 25 and 75 mg/kg. These results indicated that TFDR inhibited tumor
      growth and metastasis by protecting host immunocyte viability and its
      proliferation potential, and selectively inhibiting tumor cell proliferation, and
      improving cytolytic activity of NK cells, and enhancing TNF release in LLC
      bearing mice. Daphnodorin B and its analogues in TFDR are the active constituents
      in the roots of D. genkwa, contributing to the inhibition of tumor growth and
      metastasis.

PMID- 17178378
TI  - Antitumor activity of daphnodorins from Daphne genkwa roots.
AB  - Daphne genkwa root has been traditionally used as an effective remedy to treat
      various tumors. However, the active constituents for its antitumor potency have
      not been well documented. During the screening for antitumor constituents, it was
      found that daphnodorins were responsible for the inhibition of tumor growth and
      metastasis. In this study, six daphnodorins including daphnodorins B (1), G (2),
      H (3), H-3''-methylether (4), H-3-methylether (5) and G-3''-methylether (6) were
      investigated for the protection against LLC-induced reduction of lymphoid organs
      and peripheral lymphocytes, and for the activities against tumor growth and
      metastasis. The six daphnodorins showed selective cytotoxicity to a number of
      tumor cell lines. Treatment of LLC-bearing mice with daphnodorin B and/or
      daphnodorin complex evidently protected peripheral lymphocytes from tumor-induced
      reduction, increased lymphocyte proliferation potential and inhibited tumor
      progression and metastasis at doses of 40 and 80 mg/kg. These results indicated
      that daphnodorin B or daphnodorin complex inhibited tumor growth and metastasis
      by protecting host immunocyte viability and proliferation potential, and
      selectively inhibiting tumor cell proliferation.

PMID- 17178379
TI  - The effect of substance P on nitric oxide production by HSV-1 infected
      macrophages.
AB  - The regulatory role of neuro-immune pathways in various infectious disease states
      is an interesting area of investigation due to its important therapeutic
      potential. In this study the effect of substance P (SP) on nitric oxide (NO)
      production of HSV-infected macrophages and its relation with incubation time and
      also the cytopathic effect of virus in the presence of SP are considered. As we
      have observed, substance P enhances NO production both in HSV- and mock-infected
      macrophages and this effect has been diminished or disappeared after 24 h. It has
      also been observed that SP enhances the cytopathic effect of HSV in a time
      dependent manner with the most effect at 10 h after stimulation with SP. We have
      also observed that HSV-1 cytopathic effect has not been significantly affected by
      pretreatment of macrophages with SP (2, 10 or 24 h before HSV infection). It can
      be concluded that the neurotransmitter SP has a significant role in modulating
      macrophage function and thus innate immunity processes in healthy and HSV
      infected cells.

PMID- 17178380
TI  - Chemoprevention by cyclooxygenase-2 inhibition reduces immature myeloid
      suppressor cell expansion.
AB  - Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme activity have shown
      chemopreventive activity in carcinogen-induced and transgenic rodent tumor models
      and clinically for colon cancer. However, the mechanism(s) by which COX-2
      inhibitors reduce carcinogenesis remains controversial. We report herein that
      administration of the selective COX-2 inhibitor, celecoxib, significantly reduces
      the number of Gr1(+)CD11b(+) immature myeloid suppressor cells (IMSCs) during
      chemoprevention of 1,2-dimethylhydrazine diHCl-(1,2-DMH-) induction of large
      intestinal tumors in Swiss mice. Celecoxib administration also increased splenic
      lymphatic number and tumor infiltration by lymphocytes. The 1,2-DMH induction of
      large intestinal tumors was associated with a four-fold increase in IMSCs, and a
      decrease in splenic T cell number and function. Concordant with the changes in
      the IMSC frequency, messenger ribonucleic acid (mRNA) levels of inducible nitric
      oxide synthase (NOS-2) and arginase (Arg) were increased in the spleen of the
      tumor-bearing mice and normalized by celecoxib administration. In addition to
      delaying tumor induction, reducing tumor number, and increasing lymphocyte
      infiltration of tumors, celecoxib therapy reversed CD4(+) T cell loss, decreased
      IMSC numbers and increased mRNA levels of NOS-2 and Arg in the spleen. In
      summary, our results suggest that celecoxib chemoprevention of autochthonous
      intestinal tumors can regulate IMSCs and CD4(+) T cell numbers.

PMID- 17178381
TI  - Histidine decarboxylase-stimulating and inflammatory effects of alendronate in
      mice: involvement of mevalonate pathway, TNFalpha, macrophages, and T-cells.
AB  - Nitrogen-containing bisphosphonates (NBPs) are powerful anti-bone-resorptive
      drugs, but they frequently induce various inflammatory side effects. Recent
      clinical applications have disclosed an unexpected new side effect, jaw-bone
      necrosis and exposure. In vitro studies suggest that the inflammatory effects of
      NBPs are due to Vgamma2Vdelta2 T-cells, stimulated directly and/or indirectly
      [the latter via isopentenylpyrophosphate (IPP) in the mevalonate pathway]. Rats
      and mice, however, lack Vgamma2Vdelta2 T-cells, yet NBPs still induce necrotic
      and inflammatory reactions. In mice, NBPs induce IL-1-dependent inflammatory
      reactions, such as inductions of histidine decarboxylase (HDC, the histamine
      forming enzyme) in the liver, lung, spleen, and bone marrow, an increase in
      granulocytic cells in the peritoneal cavity, pleural exudation, and splenomegaly.
      Here, we examined the involvement of IPP, TNF, macrophages, and T-cells in the
      inflammatory actions of alendronate (a typical NBP) in mice. Various statins
      (mevalonate-synthesis inhibitors) suppressed the alendronate-induced HDC
      inductions, while mevalonate itself augmented such inductions. IPP injection also
      induced HDC. Like IL-1-deficient mice, TNF-deficient mice were resistant to
      alendronate-stimulated HDC induction. Alendronate-stimulated HDC inductions were
      significantly weaker in macrophage-depleted mice and in nude mice than in control
      mice. Similar, though generally less clear-cut, results were obtained when other
      alendronate-induced inflammatory reactions were examined. These results suggest
      that (i) inhibition of the mevalonate pathway causes and/or modifies at least
      some inflammatory actions of alendronate in mice, (ii) in addition to IL-1, TNF
      is also involved in the inflammatory actions of alendronate, and (iii)
      alendronate may act on a variety of cells, including macrophages and T-cells.

PMID- 17178382
TI  - Immunomodulatory and anticancer activities of flavonoids extracted from litchi
      (Litchi chinensis Sonn) pericarp.
AB  - The litchi pericarp extract was subjected to partition by hexane, ethyl acetate
      and water. Epicatechin, proanthocyanidin B2 and proanthocyanidin B4 were isolated
      and purified from the ethyl acetate fraction by reverse-phase high performance
      liquid chromatography. The immunomodulatory activities of epicatechin,
      proanthocyanidin B2, proanthocyanidin B4 and the ethyl acetate fraction were
      examined using proliferation of mouse splenocytes. The results showed all these
      samples had much higher stimulatory effects on splenocyte proliferation than that
      of the reference, rutin. Epicatechin and the ethyl acetate fraction showed a
      significantly (P<0.05) stimulatory effect when the concentration was up to 12.5
      micro g/ml. Proanthocyanidin B2 and proanthocyanidin B4 exhibited little lower
      stimulatory effects than epicatechin and the ethyl acetate fraction. The anti
      breast cancer activities of epicatechin, proanthocyanidin B2, proanthocyanidin B4
      and the ethyl acetate fraction were also evaluated. Epicatechin and
      proanthocyanidin B2 had lower cytotoxicities to human breast cancer cell MCF-7
      and human embryolic lung fibroblast than paclitaxel.

PMID- 17178383
TI  - Effect of pentoxifylline on differentiation and maturation of human monocyte
      derived dendritic cells in vitro.
AB  - Pentoxifylline (PTX) is a drug used for the treatment of vascular disorders, but
      it also has a positive therapeutic effect in experimental models of some
      autoimmune diseases. In this work, we studied the effect of PTX on human monocyte
      derived dendritic cells (MDDCs). Immature MDDCs were generated in vitro from
      monocytes in the presence of recombinant human granulocyte macrophage-colony
      stimulating factor (rhGM-CSF) and recombinant human interleukin-4 (rhIL-4), while
      mature MDDCs were obtained by cultivation of immature MDDCs with
      lipopolysaccharide (LPS). PTX (200 micro g/ml) was added at the beginning of cell
      cultivation. We found that PTX significantly impaired differentiation and
      function of immature MDDCs, as judged by the reduced allostimulatory activity of
      these cells on allogeneic T cells and down-regulation of costimulatory and
      adhesion molecules, such as CD86, CD40 and CD54. The maturation of MDDCs in the
      presence of PTX and LPS was characterized by the decreased expression of
      maturation marker CD83 and costimulatory molecule CD86, as well as lower
      stimulation of alloreactive T cells compared to the control MDDCs cultivated with
      LPS alone. PTX-treated MDDCs which were induced to mature with LPS produced lower
      levels of TNF-alpha, IL-12 and IL-18 and higher levels of IL-10 than
      corresponding control MDDCs. PTX did not significantly alter endocytosis of
      dextran by both immature and mature MDDCs. Cumulatively, our results show for the
      first time that PTX might impair differentiation, maturation and function of
      human MDDCs in vitro, suggesting an additional mechanism of its immunomodulatory
      activity.

PMID- 17178384
TI  - Isolation and characterization of an anti-complementary polysaccharide D3-S1 from
      the roots of Bupleurum smithii.
AB  - The preliminary data from hemolytic assays indicated that the hot-water extract
      of the roots of Bupleurum smithii had anti-complementary activity. Further
      bioactivity-guided fractionation led to the isolation of D3-S1, a homogeneous
      form of acidic polysaccharide. D3-S1 was a branched polysaccharide with average
      molecular weight about 2,000,000 Da, composed of Ara, Gal and GalA in the ratio
      of 2.6:1.0:1.2, along with trace of Rha, Glc, Xyl and Man. Methylation analysis
      and NMR identified the linkages of the residues of D3-S1. Functional analysis
      showed that D3-S1 inhibited complement activation on both the classic and
      alternative pathways with CH(50) value of 0.34+/-0.02 mg/ml and AP(50) value of
      0.081+/-0.003 mg/ml, respectively. Preliminary mechanism studies by using
      complement component depleted-sera indicated that D3-S1 selectively interacts
      with C1s, C3 and C4, but not C1q, C1r, C2, C5 and C9. The results suggested that
      D3-S1 could be of potential benefits in treatment of the complement-associated
      diseases.

PMID- 17178385
TI  - Optimisation of the sensitisation conditions for an ovalbumin challenge model of
      asthma.
AB  - Antigen inhalation in patients with atopic asthma results in an early asthmatic
      response (EAR), accompanied by a late asthmatic response (LAR) in 60% of
      patients, airway hyperresponsiveness (AHR) and inflammatory cell infiltration to
      the lungs. An ideal animal model of asthma should, therefore, provide at least
      these 4 features consistently and reproducibly. The aim of this study was to
      optimise the ovalbumin (OA) sensitisation conditions, for achieving EAR, LAR, AHR
      and cell influx, in a guinea-pig model of asthma. Animals were sensitised with 10
      micro g or 100 micro g OA, as either a single or booster (day 1 and day 5)
      injection. Airway responses to inhaled OA (10 micro g, 1 h) of actively
      sensitised, conscious guinea pigs were determined by whole body plethysmography
      as the change in specific airways conductance (sG(aw)) over a 12 h period and at
      24 h. Bronchoconstriction by inhaled histamine (1 mM) was used to investigate
      AHR, and inflammatory cell influx was determined by bronchoalveolar lavage (BAL),
      both at 24 h post-challenge. A single sensitisation with 10 micro g OA did not
      reveal an EAR, LAR or AHR following exposure to OA. However, total and
      differential cell counts (eosinophils and macrophages) were significantly greater
      24 h post-challenge, when compared to saline-challenged sensitised animals. The
      addition of a booster injection of 10 micro g revealed an EAR, but no LAR or AHR
      after ovalbumin inhalation. However, there was a significant cell influx.
      Sensitisation with 100 micro g OA (single and booster injections) revealed all
      four parameters of the asthmatic response (EAR, LAR, AHR and cell influx). The
      incorporation of the booster sensitisation injection resulted in a prolongation
      of the LAR, and the AHR was more pronounced and cell influx increased
      significantly, when compared to all other sensitisation protocols. Thus,
      sensitisation with 100 micro g OA (with a booster injection) can reveal an EAR,
      LAR, AHR and cell influx following inhalation exposure to OA (10 micro g).
      Cellular infiltration to the lung may be a poor marker of the asthmatic response,
      as a threshold level of cell influx (eosinophils) appears to be required in order
      to elicit the LAR and AHR. There was an association between the LAR and AHR.

PMID- 17178386
TI  - Preventive effects of a biscoclaurine alkaloid, cepharanthine, on endotoxin or
      tumor necrosis factor-alpha-induced septic shock symptoms: involvement of from
      cell death in L929 cells and nitric oxide production in raw 264.7 cells.
AB  - The preventive effects of cepharanthine, a biscoclaurine alkaloid isolated from
      Stephania cepharantha Hayata, on the lethality and cell death caused by endotoxin
      or tumor necrosis factor (TNF)-alpha-induced syndrome in septic shock were
      investigated. In these experiments, we estimated the survival of mice treated
      with a lethal dose of endotoxin (50 mg/kg, i.p.) or recombinant human (rh) TNF
      alpha (10,000 units/mouse, i.v.) together with a sublethal dose (1 mg/kg, i.p.)
      of endotoxin. Cepharanthine clearly protected mice from endotoxin-induced and
      endotoxin/rhTNF-alpha-induced lethal shock. In in vitro experiments,
      cepharanthine (3 micro g/ml) definitely inhibited cell death in mouse L929
      fibroblast cells incubated with rhTNF-alpha (100 units/ml) at 37 degrees C for 24
      h. On the other hand, non-apoptotic programmed death of cells was observed by
      fluorescence microscopy in rhTNF-alpha (100 units/ml)-treated L929 cells. In the
      3-(4,5-Dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay after 48
      h drug exposure, the cell proliferation of L929 cells was significantly increased
      by the addition of cepharanthine (1 and 3 micro g/ml). It seems that the
      preventive effect of cepharanthine on rhTNF-alpha-induced cytotoxicity in
      fibroblast cells occurs through an increase of cell proliferation by the drug. In
      addition, cepharanthine suppressed nitric oxide (NO) production by endotoxin
      stimulated Raw 264.7 mouse macrophage cells. These findings suggest that
      cepharanthine prevents lethality or cytotoxicity through suppression of endotoxin
      induced NO in macrophages and that its effects are possibly mediated by the
      enhancement of the proliferation of fibroblast cells. Cepharanthine may therefore
      protect against some of the various disturbances caused by endotoxin through its
      ability to inhibit NO production in septic shock.

PMID- 17178387
TI  - Trichostatin A down-regulates ZAP-70, LAT and SLP-76 content in Jurkat T cells.
AB  - We exploited Jurkat leukemia T cell clone E6-1 as a model of Trichostatin A (TSA)
      effect on cellular levels of ZAP-70, LAT and SLP-76 molecules involved in the
      signal transduction pathway from T cell receptor to nucleus. Using reverse
      transcription real-time quantitative PCR and Western blotting analysis we
      observed that TSA resulted in ZAP-70, LAT and SLP-76 transcript and protein down
      regulation in Jurkat leukemia T cells. We also found that TSA reduced half-life
      of ZAP-70, LAT and SLP-76 mRNAs from 4.8, 3.5, and 4.8 to approximately 2.3, 1.9
      and 1.7 h, respectively. Employing the protein biosynthesis inhibitor
      cycloheximide, we demonstrated the involvement of RNase and/or mRNA stabilization
      protein in ZAP-70, LAT and SLP-76 mRNAs stabilization. The effect of TSA on ZAP
      70, LAT and SLP-76 content in T cells confirms an immunosuppressive effect by
      TSA, and the usefulness of this histone deacetylase inhibitor in the treatment of
      autoimmune diseases.

PMID- 17178388
TI  - Effects of polyunsaturated fatty acids on calcium response and degranulation from
      RBL-2H3 cells.
AB  - To investigate the biological activity of various polyunsaturated fatty acids
      (PUFAs) on the allergic reaction, we examined the effects of six PUFAs and two
      saturated fatty acids on calcium response and degranulation from rat basophilic
      leukemia (RBL-2H3) cells. Between 20 and 40 microM of six PUFAs (omega-6 series:
      arachidonic acid [AA, C20:4], gamma-linolenic acid [gamma-LN, C18:3] and linoleic
      acid [LA, C18:2]; omega-3 series: alpha-linolenic acids [alpha-LN, C18:3] and
      eicosapentaenoic acid [EPA, C20:5]; and omega-9 series: oleic acid [OLE, C18:1]),
      or two saturated fatty acids (stearic acid [STA, C18:0] and arachidic acid [AD,
      C20:0]) were used to examine the effects on calcium response and degranulation
      from RBL-2H3 cells. Calcium response was monitored using the fluorescent calcium
      indicator fura-2, while degranulation was monitored by measuring histamine
      release from the cells. Three omega-6 PUFAs (AA, alpha-LN and LA) dose
      dependently increased the cytosolic free-calcium concentration and histamine
      release from RBL-2H3 cells. This phenomenon was specific to the omega-6 PUFAs,
      the omega-3 PUFAs (alpha-LA and EPA), omega-9 PUFA (OLE) and the saturated fatty
      acids (STA and AD) had no effect. The increase in the cytosolic free-calcium
      concentration caused by the omega-6 PUFAs depended on the existence of external
      calcium, cell viability and the cellular IP(3) levels remained unchanged
      throughout the experiment. These results suggest that omega-6 PUFAs work as
      direct mediators of calcium signaling pathways in RBL-2H3 cells.

PMID- 17178389
TI  - Antiangiogenic activity of Andrographis paniculata extract and andrographolide.
AB  - Inhibition of angiogenesis is currently perceived as one of the promising
      strategies in the treatment of cancer. In this study we analyzed the
      antiangiogenic activity of Andrographis paniculata extract (APE) and its major
      component andrographolide (ANDLE) using both in vitro and in vivo models.
      Intraperitoneal administration of APE and ANDLE significantly inhibited the B16F
      10 melanoma cell line induced capillary formation in C57BL/6 mice. Analysis of
      serum cytokine profile showed a drastic elevation in the proinflammatory
      cytokines such as IL-1beta, IL-6, TNF-alpha and GM-CSF and the most potent
      angiogenic factor VEGF in angiogenesis induced animals. Treatment of APE and
      ANDLE significantly reduced this elevated levels. Moreover, VEGF mRNA level in
      B16F-10 cell line showed a reduced level of expression in the presence of APE and
      ANDLE. Serum NO level which was increased in B16F-10 melanoma injected control
      animals was also found to be significantly lowered by the administration of APE
      and ANDLE. Antiangiogenic factors such as TIMP-1 and IL-2 level was elevated in
      APE and ANDLE treated angiogenesis induced animals. In the rat aortic ring assay
      APE and ANDLE inhibited the microvessel outgrowth at non toxic concentrations.
      Taken together our results demonstrate that APE and ANDLE inhibit the tumor
      specific angiogenesis by regulating the production of various pro and
      antiangiogenic factors such as proinflammatory cytokine, nitric oxide, VEGF, IL-2
      and TIMP-1.

PMID- 17178390
TI  - Inhibitory effects of eicosapentaenoic acid on lipopolysaccharide-induced
      activation in BV2 microglia.
AB  - Upon activation, microglia release proinflammatory mediators that play important
      roles in eliciting neuroinflammatory responses associated with neurodegenerative
      diseases. The anti-inflammatory properties of eicosapentaenoic acid (EPA) have
      been known, however, the effects responsible for lipopolysaccharide (LPS)-induced
      activation remain poorly understood in microglia. In the present study, we
      investigated the effects of EPA on the expression of proinflammatory mediators in
      LPS-stimulated BV2 microglia. EPA significantly inhibited the release of nitric
      oxide (NO), prostaglandin E(2) (PGE(2)) and proinflammatory cytokines such as
      interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha in a dose
      dependent manner. EPA also attenuated the production of cyclooxygenase (COX)-2,
      inducible nitric oxide synthase (iNOS) and proinflammatory cytokines at mRNA
      and/or protein levels. Moreover, EPA suppressed NF-kappaB activation by blocking
      IkappaB degradation, and also blocked the mitogen-activated protein kinases
      (MAPKs) such as ERK, p38 and JNK, and the Akt pathway. The anti-inflammatory
      properties of EPA may be useful for ameliorating neurodegenerative diseases as
      well as suppressing LPS-induced shock.

PMID- 17178392
TI  - Simvastatin inhibits NF-kappaB signaling in intestinal epithelial cells and
      ameliorates acute murine colitis.
AB  - Statins, HMG-CoA reductase inhibitors exert pleiotropic anti-inflammatory
      properties in vitro and in vivo, and are associated with the risk reduction of
      colorectal cancer. It remains unknown, however, whether statin is effective for
      the treatment of inflammatory bowel disease (IBD). Therefore, we investigated
      anti-inflammatory effects of simvastatin on intestinal epithelial cells (IEC) and
      on an experimental murine colitis model, and elucidated its molecular mechanisms.
      Simvastatin (50 micro M) significantly inhibited TNF-alpha-induced IL-8 gene
      expression in COLO 205 cells. Simvastatin (50 micro M) blocked TNF-alpha-induced
      NF-kappaB transcriptional activity, IkappaB phosphorylation/degradation and DNA
      binding activity of NF-kappaB. Administration of simvastatin significantly
      reduced the severity of dextran sulfate sodium (DSS)-induced murine colitis as
      assessed by body weight, colon length, DAI, and histology in a dose-dependent
      manner. These results suggest that simvastatin inhibits proinflammatory gene
      expression by blocking NF-kappaB signaling in IEC, and attenuates DSS-induced
      acute murine colitis. Simvastatin could be a potential agent for the treatment of
      IBD.

PMID- 17178391
TI  - Highly homologous Mycobacterium tuberculosis chaperonin 60 proteins with
      differential CD14 dependencies stimulate cytokine production by human monocytes
      through cooperative activation of p38 and ERK1/2 mitogen-activated protein
      kinases.
AB  - Tuberculosis is a chronic inflammatory and destructive disease caused by
      infection with Mycobacterium tuberculosis. We have previously shown that the
      mycobacterial chaperonin (Cpn)60.1 and 60.2 proteins stimulate human monocytes to
      secrete pro-inflammatory cytokines. Identification of the cellular mechanisms
      that contribute to the chronic inflammation characterised by myobacterial
      infection is therefore of potential therapeutic benefit. In the present study we
      have investigated the role of the extracellular signal-regulated (ERK1/2) and p38
      mitogen-activated protein kinase (MAPK) families in Cpn60-induced cytokine
      synthesis, and have compared the effects of the bacterial proteins with those of
      lipopolysaccharide (LPS). Exposure to Cpn60.1, Cpn60.2 or LPS enhanced ERK1/2
      activation with increases in phosphorylation evident between 10 and 30 min and
      maximal after 60-90 min stimulation. Phosphorylation of ERK1/2 in Cpn60
      stimulated monocytes was maintained whereas ERK1/2 was rapidly dephosphorylated
      in LPS-stimulated cells. Exposure to the chaperonins also caused rapid activation
      of p38(mapk) with kinetics of phosphorylation comparable to those observed in
      response to LPS. Selective inhibitors of p38(mapk) (SB203580) or of MEK1/2, the
      direct upstream activator of ERK1/2 (PD98059), reduced the synthesis of IL-1beta,
      TNFalpha, IL-6 and IL-8 induced by either the chaperonins or LPS. Experiments in
      which cells were exposed to a combination of both inhibitors led to a nearly
      complete abrogation of agonist-induced cytokine synthesis. These results show
      that the p38(mapk) and ERK1/2 signalling pathways are important regulators of the
      cellular response to mycobacterial chaperonins and that these pathways cooperate
      to regulate pro-inflammatory cytokine production by human monocytes.

PMID- 17178394
TI  - The immunopotentiator effects of nefopam.
AB  - The effects of opiate analgesics and non-steroidal anti-inflammatory drugs on the
      immune functions have been reported. The effect of the non-opiate analgesic
      nefopam on the immune functions has not yet been investigated. Male Swiss albino
      mice were treated with either heat killed E. coli or saline. They were classified
      into 12 groups. The effects of subacute (15 mg/kg/12 h S.C. daily for one week)
      and chronic (10 mg/kg/12 h S.C. daily for one month) treatment with nefopam on
      the levels of interferon-gamma (IFN-gamma) and total immunoglobulins were
      examined in both normal and immunized mice. Also, the effect of the chronic
      administration of nefopam on the phagocytic activity of peritoneal macrophage was
      evaluated in both normal and immunized mice. Subacute and chronic administration
      of nefopam induced no significant raise in the level of interferon-gamma (IFN
      gamma) or in the level of total immunoglobulins in non-immunized animals, while
      subacute and chronic treatment with nefopam augmented markedly the immunization
      induced increase of level of interferon-gamma (IFN-gamma). Furthermore, chronic
      treatment with nefopam potentiated significantly the production of total
      immunoglobulin induced by heat killed E. coli. Chronic treatment with nefopam
      also was associated with significant enhancement of innate immune response
      reflected in the pronounced increase in the phagocytic activity of macrophages in
      non-immunized and immunized animals. The enhancement of phagocytic activity of
      macrophages by nefopam in immunized animals was significantly higher than that of
      non-immunized animals. These findings revealed that nefopam has the ability to
      trigger the immune response for bacterial antigen. The mechanism behind the
      immunostimulatory effect of nefopam requires further investigation, but it may be
      due, at least in part, to the inhibitory effect of nefopam on the serotonin and
      norepinephrine reuptake at nerve endings. In conclusion, our findings postulated
      that nefopam stimulated the immune functions and improved the defence mechanism.
      This information may be of future therapeutic value in diseases that need
      immunologic enhancement.

PMID- 17178395
TI  - CCL21-induced immune cell infiltration.
AB  - Cellular immune responses can be initiated via peptide presentation by
      specialized antigen presenting cells, dendritic cells (DCs), which stimulate
      naive T cells. The trafficking of DCs and T cells is regulated by chemokines such
      as CCL21. CCL21 is normally expressed in the lymphoid organs and coordinates the
      interactions between DCs and T cells, thereby contributing to the initiation of T
      cell responses. In order to comprehend the mechanisms of CCL21 activity and to
      utilize CCL21 optimally in therapy, understanding the kinetics of the responses
      of various cell types to CCL21 would be beneficial. Therefore, in this study, we
      injected mice subcutaneously (s.c.) with CCL21 and examined the DC and T cell
      infiltration of the local draining lymph node. CCL21 injection resulted in
      significantly increased numbers of lymphoid and myeloid DCs and effector T
      lymphocytes in the local node at 4 days. Furthermore, at 4 days small lymphoid
      like structures were visible in the injection areas. These results provide
      guidance for the optimal timing of CCL21 use in combination with vaccines.

PMID- 17178393
TI  - CD8 blockade promotes the expansion of antigen-specific CD4+ FOXP3+ regulatory T
      cells in vivo.
AB  - Treatment with a cocktail of CD4 and CD8-specific monoclonal antibodies (mAb)
      induces long-term transplantation tolerance and regulatory CD4(+) T cells that
      induce tolerance in non-tolerant T cells. In contrast, treatment with a CD4
      specific mAb alone fails to induce long-term tolerance. The current study was
      designed to test the hypothesis that CD8 blockade plays a role in promoting the
      development of CD4(+) regulatory T cells. Using the DO11.10 CD4(+) TCR transgenic
      mouse model we show that treatment with a CD4/CD8-specific mAb cocktail induces
      antigen-specific tolerance to OVA, measured by a significant decrease in OVA
      specific IgG, on challenge with antigen. Although treatment with OVA and the CD4
      specific mAb alone also induces a significant decrease in OVA-specific antibody,
      the number of DO11.10 cells is significantly greater in mice treated with the
      CD4/CD8-specific mAb cocktail, and this is associated with a significant increase
      in proliferation of DO11.10 cells in response to specific antigen. DO11.10 cells
      sorted from mice made tolerant to OVA with the CD4/CD8-specific mAb cocktail
      promote an OVA-specific IgG1 (Th2-type) response but not an OVA-specific IgG3
      (Th1-type) response on transfer into new syngeneic recipients, suggesting their
      ability to regulate the type of antigen-specific immune response that ensues
      after priming with antigen. In addition, DO11.10 cells from tolerant mice express
      markers that are characteristic of CD4(+) regulatory cells, including FOXP3, GITR
      and CTLA4, but not CD25. Taken as a whole, these data suggest that CD8 blockade
      promotes CD4(+) FOXP3(+) regulatory CD4(+) T cells by promoting their
      proliferation in tolerant mice.

PMID- 17178396
TI  - HOW to wrap axons with crooked neck.
AB  - How can RNA processing direct specific aspects of nervous system development? In
      this issue of Neuron, Edenfeld et al. identified a novel function for two
      regulators of mRNA splicing in Drosophila: peripheral glial cells require Crooked
      neck (Crn) and Held out wings (HOW) to mediate migration and ensheathment of
      peripheral axons.

PMID- 17178397
TI  - They are not too excited: the possible role of adult-born neurons in epilepsy.
AB  - In a new study in this issue of Neuron, Jakubs and colleagues report that adult
      generated hippocampal granule cells develop particular functional properties when
      their birth is induced by epileptic seizures. The new neurons showed reduced
      excitatory synaptic input and decreased excitability. Their functional
      integration was thus adjusted to the prevailing functional state in the network.
      By this means, adult neurogenesis might contribute to network homeostasis in the
      epileptic temporal lobe.

PMID- 17178398
TI  - Channeling to the nucleus.
AB  - L-type voltage-gated calcium channels (LTCs) may control neuronal gene expression
      by increasing nuclear Ca(2+) levels or regulating Ca(2+)/calmodulin-dependent
      transcription factors. In the November 3 issue of Cell, Gomez-Ospina et al.
      demonstrate another signaling mechanism, in which a C-terminal fragment of LTC
      translocates to the nucleus in a calcium-dependent manner and directly regulates
      transcription.

PMID- 17178399
TI  - The neural basis of language development and its impairment.
AB  - The neural correlates of early language development and language impairment are
      described, with the adult language-related brain systems as a target model.
      Electrophysiological and hemodynamic studies indicate that language functions to
      be installed in the child's brain are similar to those of adults, with
      lateralization being present at birth, phonological processes during the first
      months, semantic processes at 12 months, and syntactic processes around 30
      months. These findings support the view that the brain basis of language develops
      continuously over time. Discontinuities are observed in children with language
      impairment. Here, the observed functional abnormalities are accompanied by
      structural abnormalities in inferior frontal and temporal brain regions.

PMID- 17178400
TI  - The transcription factor NFIA controls the onset of gliogenesis in the developing
      spinal cord.
AB  - The mechanisms controlling the transition from neurogenesis to gliogenesis in the
      vertebrate CNS are incompletely understood. We identified a family of
      transcription factors, called NFI genes, which are induced throughout the spinal
      cord ventricular zone (VZ) concomitantly with the induction of GLAST, an early
      marker of gliogenesis. NFIA is both necessary and sufficient for GLAST induction
      in the VZ. Unexpectedly, NFIA is also essential for the continued inhibition of
      neurogenesis in VZ progenitors. This function is mediated by the requirement of
      NFIA for the expression of HES5, a Notch effector. However, Notch effectors are
      unable to promote glial-fate specification in the absence of NFIA. Thus, NFIA
      links the abrogation of neurogenesis to a generic program of gliogenesis, in both
      astrocyte and oligodendrocyte VZ progenitors. At later stages, NFIA promotes
      migration and differentiation of astrocyte precursors, a function that is
      antagonized in oligodendrocyte precursors by Olig2.

PMID- 17178401
TI  - The splicing factor crooked neck associates with the RNA-binding protein HOW to
      control glial cell maturation in Drosophila.
AB  - In both vertebrates and invertebrates, glial cells wrap axonal processes to
      ensure electrical conductance. Here we report that Crooked neck (Crn), the
      Drosophila homolog of the yeast Clf1p splicing factor, is directing peripheral
      glial cell maturation. We show that crooked neck is expressed and required in
      glial cells to control migration and axonal wrapping. Within the cytoplasm, Crn
      interacts with the RNA-binding protein HOW and then translocates to the nucleus
      where the Crn/HOW complex controls glial differentiation by facilitating splicing
      of specific target genes. By using a GFP-exon trap approach, we identified some
      of the in vivo target genes that encode proteins localized in autocellular
      septate junctions. In conclusion, here we show that glial cell differentiation is
      controlled by a cytoplasmic assembly of splicing components, which upon
      translocation to the nucleus promote the splicing of genes involved in the
      assembly of cellular junctions.

PMID- 17178402
TI  - Essential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced
      and hippocampal axon growth.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is thought to mediate morphological
      responses to a variety of extracellular signals. Surprisingly, we found no gross
      morphological deficits in nervous system development in GSK-3beta null mice. We
      therefore designed an shRNA that targeted both GSK-3 isoforms. Strong knockdown
      of both GSK-3alpha and beta markedly reduced axon growth in dissociated cultures
      and slice preparations. We then assessed the role of different GSK-3 substrates
      in regulating axon morphology. Elimination of activity toward primed substrates
      only using the GSK-3 R96A mutant was associated with a defect in axon polarity
      (axon branching) compared to an overall reduction in axon growth induced by a
      kinase-dead mutant. Consistent with this finding, moderate reduction of GSK-3
      activity by pharmacological inhibitors induced axon branching and was associated
      primarily with effects on primed substrates. Our results suggest that GSK-3 is a
      downstream convergent point for many axon growth regulatory pathways and that
      differential regulation of primed versus all GSK-3 substrates is associated with
      a specific morphological outcome.

PMID- 17178404
TI  - The adhesion molecule CHL1 regulates uncoating of clathrin-coated synaptic
      vesicles.
AB  - In searching for binding partners of the intracellular domain of the
      immunoglobulin superfamily adhesion molecule CHL1, we identified the clathrin
      uncoating ATPase Hsc70. CHL1 gene ablation resulted in reduced targeting of Hsc70
      to the synaptic plasma membrane and synaptic vesicles, suggesting CHL1 as a
      synapse-targeting cue for Hsc70. CHL1 accumulates in presynaptic membranes and,
      in response to synapse activation, is targeted to synaptic vesicles by
      endocytosis. CHL1 deficiency or disruption of the CHL1/Hsc70 complex results in
      accumulation of abnormally high levels of clathrin-coated synaptic vesicles with
      a reduced ability to release clathrin. Generation of new clathrin-coated synaptic
      vesicles in an activity-dependent manner is inhibited when the CHL1/Hsc70 complex
      is disrupted, resulting in impaired uptake and release of FM dyes in synaptic
      boutons. Abnormalities in clathrin-dependent synaptic vesicle recycling may thus
      underlie brain malfunctions in humans and mice that carry mutations in the CHL1
      gene.

PMID- 17178405
TI  - Pacemaking by HCN channels requires interaction with phosphoinositides.
AB  - Hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channels mediate the
      depolarizing cation current (termed I(h) or I(f)) that initiates spontaneous
      rhythmic activity in heart and brain. This function critically depends on the
      reliable opening of HCN channels in the subthreshold voltage-range. Here we show
      that activation of HCN channels at physiologically relevant voltages requires
      interaction with phosphoinositides such as phosphatidylinositol-4,5-bisphosphate
      (PIP(2)). PIP(2) acts as a ligand that allosterically opens HCN channels by
      shifting voltage-dependent channel activation approximately 20 mV toward
      depolarized potentials. Allosteric gating by PIP(2) occurs in all HCN subtypes
      and is independent of the action of cyclic nucleotides. In CNS neurons and
      cardiomyocytes, enzymatic degradation of phospholipids results in reduced channel
      activation and slowing of the spontaneous firing rate. These results demonstrate
      that gating by phospholipids is essential for the pacemaking activity of HCN
      channels in cardiac and neuronal rhythmogenesis.

PMID- 17178406
TI  - Block of kainate receptor desensitization uncovers a key trafficking checkpoint.
AB  - A prominent feature of ionotropic glutamate receptors from the AMPA and kainate
      subtypes is their profound desensitization in response to glutamate-a process
      thought to protect the neuron from overexcitation. In AMPA receptors, it is well
      established that desensitization results from rearrangements of the interface
      formed between agonist-binding domains of adjacent subunits; however, it is
      unclear how this mechanism applies to kainate receptors. Here we show that
      stabilization of the binding domain dimer by the generation of intermolecular
      disulfide bonds apparently blocked desensitization of the kainate receptor GluR6.
      This result establishes a common desensitization mechanism in both AMPA and
      kainate receptors. Surprisingly, however, surface expression of these
      nondesensitizing mutants was drastically reduced and did not depend on channel
      activity. Therefore, in addition to its role at the synapse, we now propose an
      intracellular role for desensitization in controlling maturation and trafficking
      of glutamate receptors.

PMID- 17178403
TI  - Staufen- and FMRP-containing neuronal RNPs are structurally and functionally
      related to somatic P bodies.
AB  - Local control of mRNA translation modulates neuronal development, synaptic
      plasticity, and memory formation. A poorly understood aspect of this control is
      the role and composition of ribonucleoprotein (RNP) particles that mediate
      transport and translation of neuronal RNAs. Here, we show that staufen- and FMRP
      containing RNPs in Drosophila neurons contain proteins also present in somatic "P
      bodies," including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial
      components of miRNA (argonaute), NMD (Upf1p), and general translational
      repression (Dhh1p/Me31B) pathways. Drosophila Me31B is shown to participate (1)
      with an FMRP-associated, P body protein (Scd6p/trailer hitch) in FMRP-driven,
      argonaute-dependent translational repression in developing eye imaginal discs;
      (2) in dendritic elaboration of larval sensory neurons; and (3) in bantam miRNA
      mediated translational repression in wing imaginal discs. These results argue for
      a conserved mechanism of translational control critical to neuronal function and
      open up new experimental avenues for understanding the regulation of mRNA
      function within neurons.

PMID- 17178407
TI  - Environment matters: synaptic properties of neurons born in the epileptic adult
      brain develop to reduce excitability.
AB  - Neural progenitors in the adult dentate gyrus continuously produce new functional
      granule cells. Here we used whole-cell patch-clamp recordings to explore whether
      a pathological environment influences synaptic properties of new granule cells
      labeled with a GFP-retroviral vector. Rats were exposed to a physiological
      stimulus, i.e., running, or a brain insult, i.e., status epilepticus, which gave
      rise to neuronal death, inflammation, and chronic seizures. Granule cells formed
      after these stimuli exhibited similar intrinsic membrane properties. However, the
      new neurons born into the pathological environment differed with respect to
      synaptic drive and short-term plasticity of both excitatory and inhibitory
      afferents. The new granule cells formed in the epileptic brain exhibited
      functional connectivity consistent with reduced excitability. We demonstrate a
      high degree of plasticity in synaptic inputs to adult-born new neurons, which
      could act to mitigate pathological brain function.

PMID- 17178408
TI  - Dynamic role of postsynaptic caspase-3 and BIRC4 in zebra finch song-response
      habituation.
AB  - Activation of the protease caspase-3 is commonly thought to cause apoptotic cell
      death. Here, we show that caspase-3 activity is regulated at postsynaptic sites
      in brain following stimuli associated with memory (neural activation and
      subsequent response habituation) instead of cell death. In the zebra finch
      auditory forebrain, the concentration of caspase-3 active sites increases briefly
      within minutes after exposure to tape-recorded birdsong. With confocal and
      immunoelectron microscopy, we localize the activated enzyme to dendritic spines.
      The activated caspase-3 protein is present even in unstimulated brain but bound
      to an endogenous inhibitor, BIRC4 (xIAP), suggesting a mechanism for rapid
      release and sequestering at specific synaptic sites. Caspase-3 activity is
      necessary to consolidate a persistent physiological trace of the song stimulus,
      as demonstrated using pharmacological interference and the zenk gene habituation
      assay. Thus, the brain appears to have adapted a core component of cell death
      machinery to serve a unique role in learning and memory.

PMID- 17178409
TI  - Brightness induction: rate enhancement and neuronal synchronization as
      complementary codes.
AB  - In cat visual cortex, we investigated with parallel recordings from multiple
      units the neuronal correlates of perceived brightness. The perceived brightness
      of a center grating was changed by varying the orientation or the relative
      spatial phase of a surrounding grating. Brightness enhancement by orientation
      contrast is associated with an increase of discharge rates of responses to the
      center grating but not with changes in spike synchronization. In contrast, if
      brightness enhancement is induced by phase offset, discharge rates are unchanged
      but synchronization increases between neurons responding to the center grating.
      The changes in synchronization correlate well with changes in perceived
      brightness that were assessed in parallel in human subjects using the same
      stimuli. These results indicate that in cerebral cortex the modulation of
      synchronicity of responses is used as a mechanism complementary to rate changes
      to enhance the saliency of neuronal responses.

PMID- 17178410
TI  - A central source of movement variability.
AB  - Movements are universally, sometimes frustratingly, variable. When such
      variability causes error, we typically assume that something went wrong during
      the movement. The same assumption is made by recent and influential models of
      motor control. These posit that the principal limit on repeatable performance is
      neuromuscular noise that corrupts movement as it occurs. An alternative
      hypothesis is that movement variability arises before movements begin, during
      motor preparation. We examined this possibility directly by recording the
      preparatory activity of single cortical neurons during a highly practiced reach
      task. Small variations in preparatory neural activity were predictive of small
      variations in the upcoming reach. Effect magnitudes were such that at least half
      of the observed movement variability likely had its source during motor
      preparation. Thus, even for a highly practiced task, the ability to repeatedly
      plan the same movement limits our ability to repeatedly execute the same
      movement.

PMID- 17178411
TI  - Learning to smell the roses: experience-dependent neural plasticity in human
      piriform and orbitofrontal cortices.
AB  - It is widely presumed that odor quality is a direct outcome of odorant structure,
      but human studies indicate that molecular knowledge of an odorant is not always
      sufficient to predict odor quality. Indeed, the same olfactory input may generate
      different odor percepts depending on prior learning and experience. Combining
      functional magnetic resonance imaging with an olfactory paradigm of perceptual
      learning, we examined how sensory experience modifies odor perception and odor
      quality coding in the human brain. Prolonged exposure to a target odorant
      enhanced perceptual differentiation for odorants related in odor quality or
      functional group, an effect that was paralleled by learning-induced response
      increases in piriform cortex and orbitofrontal cortex (OFC). Critically, the
      magnitude of OFC activation predicted subsequent improvement in behavioral
      differentiation. Our findings suggest that neural representations of odor quality
      can be rapidly updated through mere perceptual experience, a mechanism that may
      underlie the development of odor perception.

PMID- 17178413
TI  - Alterations in the choroid in hypercholesterolemic rabbits: reversibility after
      normalization of cholesterol levels.
AB  - Endothelial damage in atherosclerosis is characterized by abnormal vascular
      functionality. Hyperlipidemic patients show alterations in ocular
      vascularization. However, it is not known whether these alterations are
      reversible after the lipid profile returns to normal. This study evaluates a
      rabbit model of hypercholesterolemia, examining the ultrastructural changes in
      the choroid, and the changes in it after a period of normal blood-cholesterol
      values induced by a standard diet. Rabbits were divided into three groups: G0,
      fed a standard diet; G1A, fed a 0.5% cholesterol-enriched diet for 8 months; and
      G1B, fed a 0.5% cholesterol-enriched diet for 8 months followed by a standard
      diet for a further 6 months. Eyes were processed for transmission electron
      microscopy. G1A had a buildup of lipids at the suprachoroidea that compressed the
      vascular layers, and hypertrophy of endothelial and vascular smooth muscle cells.
      In G1B there was less lipid accumulation than in G1A, but this was not followed
      by reversal of the choroidal damage. The suprachoroidea thickness of G1B was
      still greater than in G0 due to abundant collagen fibers. The intervascular
      spaces of the choroid had fewer lipids than G1A but more collagen fibers than G0.
      The large- and medium-sized vessel layers and choriocapillaris were less
      compressed than in G1A but exhibited basal membrane and endothelial changes
      similar to those in G1A. Normalization of serum cholesterol levels is not enough
      to reverse cholesterol-induced vascular damage to the choroid. These choroidal
      changes could be compatible with a chronic ischemia that could produce retinal
      degeneration.

PMID- 17178414
TI  - Retinal ischemic injury rescued by sodium 4-phenylbutyrate in a rat model.
AB  - Retinal ischemia is a common cause of visual impairment for humans and animals.
      Herein, the neuroprotective effects of phenylbutyrate (PBA) upon retinal ischemic
      injury were investigated using a rat model. Retinal ganglion cells (RGCs) were
      retrograde labeled with the fluorescent tracer fluorogold (FG) applied to the
      superior collicoli of test Sprague-Dawley rats. High intraocular pressure and
      retinal ischemia were induced seven days subsequent to such FG labeling. A dose
      of either 100 or 400 mg/kg PBA was administered intraperitoneally to test rats at
      two time points, namely 30 min prior to the induction of retinal ischemia and 1 h
      subsequent to the cessation of the procedure inducing retinal ischemia. The test
      rat retinas were collected seven days subsequent to the induction of retinal
      ischemia, and densities of surviving RGCs were estimated by counting FG-labeled
      RGCs within the retina. Histological analysis revealed that ischemic injury
      caused the loss of retinal RGCs and a net decrease in retinal thickness. For PBA
      treated groups, almost 100% of the RGCs were preserved by a pre-ischemia
      treatment with PBA (at a dose of either 100 or 400 mg/kg), while post-ischemia
      treatment of RGCs with PBA did not lead to the preservation of RGCs from ischemic
      injury by PBA as determined by the counting of whole-mount retinas. Pre-ischemia
      treatment of RGCs with PBA (at a dose of either 100 or 400 mg/kg) significantly
      reduced the level of ischemia-associated loss of thickness of the total retina,
      especially the inner retina, and the inner plexiform layer of retina. Besides,
      PBA treatment significantly reduced the ischemia-induced loss of cells in the
      ganglion-cell layer of the retina. Taken together, these results suggest that PBA
      demonstrates a marked neuroprotective effect upon high intraocular pressure
      induced retinal ischemia when the PBA is administered prior to ischemia
      induction.

PMID- 17178412
TI  - Isolation of a central bottleneck of information processing with time-resolved
      FMRI.
AB  - When humans attempt to perform two tasks at once, execution of the first task
      usually leads to postponement of the second one. This task delay is thought to
      result from a bottleneck occurring at a central, amodal stage of information
      processing that precludes two response selection or decision-making operations
      from being concurrently executed. Using time-resolved functional magnetic
      resonance imaging (fMRI), here we present a neural basis for such dual-task
      limitations, e.g. the inability of the posterior lateral prefrontal cortex, and
      possibly the superior medial frontal cortex, to process two decision-making
      operations at once. These results suggest that a neural network of frontal lobe
      areas acts as a central bottleneck of information processing that severely limits
      our ability to multitask.

PMID- 17178415
TI  - Strategies for interfacing solid-phase microextraction with liquid
      chromatography.
AB  - Solid-phase microextraction (SPME) techniques are equally applicable to both
      volatile and non-volatile analytes, but the progress in applications to gas-phase
      separations has outpaced that of liquid-phase separations. The interfacing of
      SPME to gas chromatographic equipment has been straight-forward, requiring little
      modification of existing equipment. The requirement of solvent desorption for non
      volatile or thermally labile analytes has, however, proven challenging for
      interfacing SPME with liquid-phase separations. Numerous options to achieve this
      have been described in the literature over the past decade, with applications in
      several different areas of analysis. To date, no single strategy or interface
      device design has proven optimal. During method development analysts must select
      the most appropriate interfacing technique among the options available. Out of
      these options three general strategies have emerged: (1) use of a manual
      injection interface tee; (2) in-tube SPME; and (3) off-line desorption followed
      by conventional liquid injection. In addition, there has been interest in
      coupling SPME directly to electrospray ionisation and matrix-assisted laser
      desorption ionisation (MALDI) for mass spectrometry. Several examples of each of
      these strategies are reviewed here, and an overview of their use and application
      is presented.

PMID- 17178416
TI  - A method of test for residual isophorone diisocyanate trimer in new polyester
      polyurethane coatings on light metal packaging using liquid chromatography with
      tandem mass spectrometric detection.
AB  - A method of test for residual isophorone diisocyanate (IPDI) trimer in
      experimental formulation polyester-polyurethane (PEPU) thermoset coatings on
      metal food packaging is described. The method involves extraction of coated
      panels using acetonitrile containing dibutylamine for concurrent derivatisation,
      and then high performance liquid chromatography with electrospray ionisation
      tandem mass spectrometric detection (LC-MS/MS). Single laboratory validation was
      carried out using three different experimental PEPU-based coatings. The
      calibrations were linear, the analytical recovery was good, no interferences were
      seen, and substance identification criteria were met. The detection limit of the
      method is around 0.02 micro g/100 cm(2) of coating, which for a typical sized can
      and assuming complete migration of any residual IPDI trimer, corresponds to about
      0.2 micro g/kg food or beverage. Separate studies indicated that, even if
      migration occurred at such low levels, the IPDI trimer would not be expected to
      persist in canned aqueous or fatty foodstuffs as it would hydrolyse to the
      corresponding aliphatic amine or react with food components to destroy the
      isocyanate moiety. The method of test developed here for residual IPDI trimer in
      thermoset polyester-polyurethane coatings should prove to be a valuable tool for
      investigating the cure kinetics of these novel coatings and help to guide the
      development of enhanced formulations.

PMID- 17178417
TI  - Selective ultratrace detection of Al(III) and Ga(III) complexed with a calcein
      isomer by capillary zone electrophoresis with laser-induced fluorescence
      detection. Comparison of emissive polyaminocarboxylates as derivatizing ligands.
AB  - A highly sensitive and selective capillary zone electrophoresis with laser
      induced fluorescence detection (CZE-LIF) for Al(3+) and Ga(3+) was developed
      using a calcein 4',5'-isomer as a pre-capillary complexing agent. Direct
      fluorescent detection without an agent added to the carrier buffer provided the
      notable detection limits of 3.9x10(-10) and 4.6x10(-10)moldm(-3) for Al and Ga,
      respectively. By applying this system successfully to a river water sample, its
      potential for practical applications was ascertained. A comparison of three
      aromatic polyaminocarboxylate ligands related to the coordination structure and
      the distance between the fluorophore and the chelating moiety, revealed some
      interesting factors regarding their selectivity.

PMID- 17178419
TI  - Inefficient response inhibition in individuals with mild cognitive impairment.
AB  - Individuals diagnosed with mild cognitive impairment (MCI) show primary deficits
      in memory and are at increased risk for developing Alzheimer's disease (AD). In
      light of recent evidence that executive cognitive deficits are common in AD and
      may be detectable in individuals diagnosed with MCI, we extend these findings to
      the investigation of response inhibition, an essential aspect of executive
      cognitive control. Twenty MCI patients and 20 healthy controls (HC) completed an
      arrow version of the flanker task [Eriksen, B. A., & Eriksen, C. W. (1974).
      Effects of noise letters upon the identification of target letters in a non
      search task. Perception & Psychophysics, 16, 143-149] in which participants
      responded to a target arrow surrounded by distractors (i.e., flankers) that
      signaled a same (congruent) or a conflicting (incongruent) response. Reaction
      time (RT) increased in both groups when flankers signaled an incongruent
      response, but more so among MCI patients. MCI patients taking a cholinesterase
      inhibitor showed smaller flanker interference effects than those not taking this
      medication. Analysis of the flanker effect as a function of the entire RT
      distribution indicated that MCI patients show increasing interference at the
      slowest segments of the distribution, a finding that implicates deficient
      inhibition of the incongruent response [Ridderinkhof, K. R. (2002). Activation
      and suppression in conflict tasks: Empirical clarification through distributional
      analyses. In W. Prinz & B. Hommel (Eds.), Common mechanisms in perception and
      action. Attention & performance, Vol. XIX (pp. 494-519). Oxford: Oxford
      University Press]. These results suggest that deficits in response inhibition are
      detectable in MCI patients and merit further investigation as to whether these
      changes aid prediction of which MCI patients convert to AD.

PMID- 17178418
TI  - Antimutagenicity of cinnamaldehyde and vanillin in human cells: Global gene
      expression and possible role of DNA damage and repair.
AB  - Vanillin (VAN) and cinnamaldehyde (CIN) are dietary flavorings that exhibit
      antimutagenic activity against mutagen-induced and spontaneous mutations in
      bacteria. Although these compounds were antimutagenic against chromosomal
      mutations in mammalian cells, they have not been studied for antimutagenesis
      against spontaneous gene mutations in mammalian cells. Thus, we initiated studies
      with VAN and CIN in human mismatch repair-deficient (hMLH1(-)) HCT116 colon
      cancer cells, which exhibit high spontaneous mutation rates
      (mutations/cell/generation) at the HPRT locus, permitting analysis of
      antimutagenic effects of agents against spontaneous mutation. Long-term (1-3
      weeks) treatment of HCT116 cells with VAN at minimally toxic concentrations (0.5
      2.5mM) reduced the spontaneous HPRT mutant fraction (MF, mutants/10(6) survivors)
      in a concentration-related manner by 19-73%. A similar treatment with CIN at 2.5
      7.5microM yielded a 13-56% reduction of the spontaneous MF. Short-term (4-h)
      treatments also reduced the spontaneous MF by 64% (VAN) and 31% (CIN). To
      investigate the mechanisms of antimutagenesis, we evaluated the ability of VAN
      and CIN to induce DNA damage (comet assay) and to alter global gene expression
      (Affymetrix GeneChip) after 4-h treatments. Both VAN and CIN induced DNA damage
      in both mismatch repair-proficient (HCT116+chr3) and deficient (HCT116) cells at
      concentrations that were antimutagenic in HCT116 cells. There were 64 genes whose
      expression was changed similarly by both VAN and CIN; these included genes
      related to DNA damage, stress responses, oxidative damage, apoptosis, and cell
      growth. RT-PCR results paralleled the Affymetrix results for four selected genes
      (HMOX1, DDIT4, GCLM, and CLK4). Our results show for the first time that VAN and
      CIN are antimutagenic against spontaneous mutations in mammalian (human) cells.
      These and other data lead us to propose that VAN and CIN may induce DNA damage
      that elicits recombinational DNA repair, which reduces spontaneous mutations.

PMID- 17178421
TI  - Molecular and biochemical analysis of rainbow trout LCK suggests a conserved
      mechanism for T-cell signaling in gnathostomes.
AB  - Two genes were identified in rainbow trout that display high sequence identity to
      vertebrate Lck. Both of the trout Lck transcripts are associated with lymphoid
      tissues and were found to be highly expressed in IgM-negative lymphocytes. In
      vitro analysis of trout lymphocytes indicates that trout Lck mRNA is up-regulated
      by T-cell mitogens, supporting an evolutionarily conserved function for Lck in
      the signaling pathways of T-lymphocytes. Here, we describe the generation and
      characterization of a specific monoclonal antibody raised against the N-terminal
      domains of recombinant trout Lck that can recognize Lck protein(s) from trout
      thymocyte lysates that are similar in size ( approximately 57kDa) to mammalian
      Lck. This antibody also reacted with permeabilized lymphocytes during FACS
      analysis, indicating its potential usage for cellular analyses of trout
      lymphocytes, thus representing an important tool for investigations of salmonid T
      cell function.

PMID- 17178422
TI  - Verification of functional AAV-mediated neurotrophic and anti-apoptotic factor
      expression.
AB  - The use of viral vectors for gene delivery offer many advantages for both basic
      research and therapeutic application through the continuous expression of a gene
      product within a target region. It is vital however that any gene product is
      correctly expressed in a biologically active form, and this should be confirmed
      prior to large scale in vivo studies. Using adeno-associated viral (AAV) vectors
      to direct the expression of either a neurotrophic factor or an anti-apoptotic
      protein, we have developed a range of in vitro assays to verify functional
      transgenic protein expression. Brain-derived neurotropic factor (BDNF) activity
      was confirmed by demonstrating enhanced generation of GABAergic neurons in
      embryonic (E15) striatal cultures and AAV-mediated glial-derived neurotrophic
      factor (GDNF) function using an assay for dopaminergic differentiation of
      embryonic (E14) ventral mesencephalic cultures. To assess functional anti
      apoptotic factor expression we designed cell-survival assays, using embryonic
      cortical cultures to confirm Bcl-x(L) activity and the HT1080 cell-line for X
      linked inhibitor of apoptosis protein (XIAP) activity following AAV-mediated
      expression. This study demonstrates that the use of functional assays provides
      valuable confirmation of desired biotherapeutic expression prior to extensive
      investigation with new gene delivery vectors.

PMID- 17178420
TI  - Dissociable effects of phonetic competition and category typicality in a phonetic
      categorization task: an fMRI investigation.
AB  - The current study used fMRI to explore the extent to which neural activation
      patterns in the processing of speech are driven by the quality of a speech sound
      as a member of its phonetic category, that is, its category typicality, or by the
      competition inherent in resolving the category membership of stimuli which are
      similar to other possible speech sounds. Subjects performed a phonetic
      categorization task on synthetic stimuli ranging along a voice-onset time
      continuum from [da] to [ta]. The stimulus set included sounds at the extreme ends
      of the voicing continuum which were poor phonetic category exemplars, but which
      were minimally competitive, stimuli near the phonetic category boundary, which
      were both poor exemplars of their phonetic category and maximally competitive,
      and stimuli in the middle of the range which were good exemplars of their
      phonetic category. Results revealed greater activation in bilateral inferior
      frontal areas for stimuli with the greatest degree of competition, consistent
      with the view that these areas are involved in selection between competing
      alternatives. In contrast, greater activation was observed in bilateral superior
      temporal gyri for the least prototypical phonetic category exemplars,
      irrespective of competition, consistent with the view that these areas process
      the acoustic-phonetic details of speech to resolve a token's category membership.
      Taken together, these results implicate separable neural regions in two different
      aspects of phonetic categorization.

PMID- 17178423
TI  - Cortical stimulation mapping using epidurally implanted thin-film microelectrode
      arrays.
AB  - Stimulation mapping of motor cortex is an important tool for assessing motor
      cortex physiology. Existing techniques include intracortical microstimulation
      (ICMS) which has high spatial resolution but damages cortical integrity by needle
      penetrations, and transcranial stimulation which is non-invasive but lacks
      focality and spatial resolution. A minimally invasive epidural microstimulation
      (EMS) technique using chronically implanted polyimide-based thin-film
      microelectrode arrays (72 contacts) was tested in rat motor cortex and compared
      to ICMS within individual animals. Results demonstrate reliable mapping with high
      reproducibility and validity with respect to ICMS. No histological evidence of
      cortical damage and the absence of motor deficits as determined by performance of
      a motor skill reaching task, demonstrate the safety of the method. EMS is
      specifically suitable for experiments integrating electrophysiology with
      behavioral and molecular biology techniques.

PMID- 17178424
TI  - Simple and inexpensive hardware and software method to measure volume changes in
      Xenopus oocytes expressing aquaporins.
AB  - Water channels (aquaporins) family members have been identified in central
      nervous system cells. A classic method to measure membrane water permeability and
      its regulation is to capture and analyse images of Xenopus laevis oocytes
      expressing them. Laboratories dedicated to the analysis of motion images usually
      have powerful equipment valued in thousands of dollars. However, some scientists
      consider that new approaches are needed to reduce costs in scientific labs,
      especially in developing countries. The objective of this work is to share a very
      low-cost hardware and software setup based on a well-selected webcam, a hand-made
      adapter to a microscope and the use of free software to measure membrane water
      permeability in Xenopus oocytes. One of the main purposes of this setup is to
      maintain a high level of quality in images obtained at brief intervals (shorter
      than 70 ms). The presented setup helps to economize without sacrificing image
      analysis requirements.

PMID- 17178425
TI  - Exposure to domoic acid affects larval development of king scallop Pecten maximus
      (Linnaeus, 1758).
AB  - Domoic acid (DA) is a highly toxic phycotoxin produced by bloom forming marine
      diatoms Pseudo-nitzschia spp. Bivalves can accumulate this toxin to a high level
      through their feeding activities, and thus illness or death in can occur in
      consumers of bivalves. In this study, king scallop, Pecten maximus, larvae were
      exposed to dissolved domoic acid (DA) for 25d, and the toxin accumulation and
      effects of harbouring this toxin were investigated. Scallop larvae incorporated
      DA continuously during the larval culture period and accumulated a maximum DA
      level of 5.21pgind(-1) when exposed to a solution of 50ngml(-1) dissolved DA. As
      a result of the DA treatment, larval growth, measured in terms of shell length
      and the appearance of the eye-spot, and larval survival were significantly
      compromised. This is the first study on DA incorporation dynamics in P. maximus
      larvae, signifying the potential of using shellfish larvae for the study on
      mechanisms of phycotoxin accumulation. The negative effect of DA exposure
      suggests that this toxin could possibly influence natural recruitment in P.
      maximus, and it may be necessary to protect hatchery-cultured scallop larvae from
      DA during toxic Pseudo-nitzschia blooms.

PMID- 17178426
TI  - The policy environment encouraging C-section in Lebanon.
AB  - OBJECTIVE: This study aims to analyse the environment encouraging C-section in
      Lebanon and to reveal approaches that could be adopted for the reduction of this
      practice, by considering the attitudes, opinions and actions of different
      stakeholders. METHODS: Semi-structured interviews were conducted with 20 selected
      key players, including hospital directors, midwives, insurance bodies, syndicates
      and scientific societies, ministries, international agencies, medical schools,
      media representatives and women's groups. In addition, a group discussion was
      conducted with 10 obstetricians. Semi-structured interviews were conducted with a
      convenience sample of 36 women who had a C-section within 4 months preceding the
      study. Data was analysed using the Policy Maker software version 2.3. RESULTS:
      Findings of the study point to the role of multiple factors in shaping the
      current practices related to C-section deliveries, among which are the
      organisation of the health care system, the dominance of the private sector, the
      lack of physician accountability, the minimisation of midwives' roles in the
      process and women's misconceptions about C-sections. CONCLUSIONS: Involvement of
      the diversity of players is important to change practices in maternity care in
      Lebanon, after considering their position and power. Different strategies making
      use of available opportunities to improve the current situation are discussed.

PMID- 17178427
TI  - Successful decolonization of methicillin-resistant Staphylococcus aureus in
      paediatric patients with cystic fibrosis (CF) using a three-step protocol.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is recognized as a bacterial
      pathogen in patients with cystic fibrosis (CF) although its clinical effects can
      be variable. The aim of this study was to evaluate the efficacy of a three-step
      decolonization protocol for MRSA (Belfast CF MRSA decolonization protocol). Of
      the 17 paediatric patients treated during the five years of the study, eight
      (47%) were successfully decolonized following one five-day course of oral
      rifampicin and fusidic acid. The success rate increased to 12 (71%) patients
      after a second five-day oral treatment course in the 11 patients who remained
      culture positive at the end of the first treatment cycle. In a further four
      patients, clearance was achieved with a course of intravenous teicoplanin,
      increasing the decolonization rate to 16 of 17 patients (94%). These results
      compare favourably with other published studies and show that MRSA decolonization
      can be successful in a high proportion of paediatric CF patients.

PMID- 17178428
TI  - Occupational exposures to bloodborne pathogens among healthcare workers in Rio de
      Janeiro, Brazil.
AB  - Healthcare workers (HCWs) frequently face the risk of occupational infection from
      bloodborne pathogens following exposure to blood and body fluids. This study
      describes the results of a surveillance system of occupational exposure to
      bloodborne pathogens among HCWs in Rio de Janeiro, Brazil, during an eight-year
      period. A total of 15 035 exposures reported from 537 health units were reviewed.
      Six circumstances comprised nearly 70% of the reported exposures: recapping
      needles (14%), performing surgical procedures or handling surgical equipment
      (14%), handling trash (13%), during disposal into sharps containers (13%),
      performing percutaneous venepuncture (10%) and during blood drawing (5%). Easily
      preventable exposures, such as incidents related to recapping needles, handling
      trash, and sharps left in an inappropriate place, represented 30% of the
      exposures reported. Post-exposure prophylaxis (PEP) for human immunodeficiency
      virus (HIV) was initiated for 46% of exposed HCWs. Although Brazilian guidelines
      indicate that PEP is usually not recommended for exposures with insignificant or
      very low risk of HIV infection, PEP was prescribed to a large proportion of
      exposed HCWs under these circumstances. The prevention of occupational exposure
      to bloodborne pathogens among HCWs and their safety must be considered as a
      public health issue. Although infection-preventative measures such as
      antiretroviral drugs and rapid tests are available, this study shows that there
      are still a high number of easily preventable exposures. The implementation of
      more effective prevention strategies is urgently required in this country.

PMID- 17178429
TI  - Reduced fungal contamination of the indoor environment with the Plasmair system
      (Airinspace).
AB  - Aspergillus spp. and other moulds cause life-threatening opportunistic infections
      in immunocompromised patients. Indoor contamination and construction work that
      liberate fungal spores are a major source of nosocomial aspergillosis. Dijon
      hospital is a tertiary care institution in northeast France undergoing
      construction work beside high-risk clinical units. To determine the impact of
      this activity, a surveillance programme was implemented one year before building
      work began in order to establish baseline levels of contamination. Air and
      surface fungal contamination in adult and paediatric haematology units were
      prospectively examined following use, or not, of a new air-treatment system with
      mobile Plasmair units (Airinspace). There were significant reductions in overall
      fungal contamination for the Plasmair treated rooms for air and surface samples
      in both clinical units. Plasmair treatment also significantly reduced A.
      fumigatus in the air. These data suggest that Plasmair units may provide an
      efficient method of reducing indoor fungal contamination in hospitals.

PMID- 17178431
TI  - Vaccine potential for inactivated shigellae.
AB  - We used human monocyte-derived dendritic cells (DC) and Balb/c mice as models to
      establish the immunogenic and protective potential of formalin-inactivated
      Shigella spp. Incubation of DC with inactivated or live bacteria induced DC
      maturation and cytokine release. Mice immunized orally or intranasally with
      killed S. flexneri, S. sonnei, or S. dysenteriae developed IgG and fecal IgA
      titers to the homologous LPS. Following respiratory challenge with the live
      homologous organisms, 80-100% survival was seen in all vaccinated groups compared
      to negligible survival in mice given PBS. Oral or intranasal immunization with an
      inactivated S. flexneri 2a strain (CVD1203) expressing the CFA/I and CS3 antigens
      of enterotoxigenic Escherichia coli induced IgG responses to both heterologous
      antigens. These in vivo and in vitro data indicate that inactivated shigellae
      retain the ability to interact effectively with key antigen presenting cells and
      induce protective immune responses in mice.

PMID- 17178432
TI  - Evaluation of the precision-cut liver and lung slice systems for the study of
      induction of CYP1, epoxide hydrolase and glutathione S-transferase activities.
AB  - The principal objective was to ascertain whether precision-cut tissue slices can
      be used to evaluate the potential of chemicals to induce CYP1, epoxide hydrolase
      and glutathione S-transferase activities, all being important enzymes involved in
      the metabolism of polycyclic aromatic hydrocarbons. Precision-cut rat liver and
      lung slices were incubated with a range of benzo[a]pyrene concentrations for
      various time periods. A rise in the O-deethylation of ethoxyresorufin was seen in
      both liver and lung slices exposed to benzo[a]pyrene, which was accompanied by
      increased CYP1A apoprotein levels. Pulmonary CYP1B1 apoprotein levels and hepatic
      mRNA levels were similarly enhanced. Elevated epoxide hydrolase and glutathione S
      transferase activities were also observed in liver slices following incubation
      for 24h; similarly, a rise in apoprotein levels of both enzymes was evident, peak
      levels occurring at the same time point. When mRNA levels were monitored, a rise
      in the levels of both enzymes was seen as early as 4h after incubation, but
      maximum levels were attained at 24 h. In lung slices, induction of epoxide
      hydrolase by benzo[a]pyrene was observed after a 24-h incubation, and at a
      concentration of 1 microM; a rise in apoprotein levels was seen at this time
      point. Glutathione S-transferase activity was not inducible in lung slices by
      benzo[a]pyrene but a modest increase was observed in hepatic slices.
      Collectively, these studies confirmed CYP1A induction in rat liver slices and
      established that CYP1B1 expression, and epoxide hydrolase and glutathione S
      transferase activities are inducible in precision-cut tissue slices.

PMID- 17178430
TI  - II. Temporal patterns of longitudinal change in aging brain function.
AB  - Time-dependent changes in brain activity were assessed in a group of older adults
      who maintained good physical and cognitive health at years 1, 3, 5, 7, and 9 of
      the Baltimore Longitudinal Study of Aging neuroimaging study. Each year, these
      participants underwent PET scans during rest and delayed verbal and figural
      recognition memory conditions. While memory performance remained stable over the
      8 years, both generalized and modality-specific patterns of time-dependent
      changes in regional cerebral blood flow (rCBF) were found. Many brain regions
      showed steady, progressive changes in rCBF over the 8 years while others
      maintained rCBF for a number of years before showing incremental declines or
      increases in activity. These temporal patterns of change were observed in many
      regions of the brain, particularly in the frontal and temporal lobes, suggesting
      that there are distinctive patterns of age-related functional decline and
      compensatory activity over time. The precise patterns of regional involvement and
      the temporal dynamics of rCBF change within specific regions vary based on
      cognitive processing demands.

PMID- 17178433
TI  - An integrated assessment model of carbon sequestration benefits: a case study of
      Liping county, China.
AB  - This research attempts to model the complexity of planting trees to increase
      China's CO(2) sequestration potential by using a GIS-based integrated assessment
      (IA) approach. We use the IA model to assess the impact of China's Grain for
      Green reforestation and afforestation program on farmer and state incomes as well
      as CO(2) sequestration in Liping County, Guizhou Province. The IA model consists
      of five sub-models for carbon sequestration, crop income, timber income, Grain
      for Green, and carbon credits. It also includes a complementary qualitative
      module for assessing program impacts by gender and ethnicity. Using four
      scenarios with various assumptions about types of trees planted, crop incomes by
      township, CO(2) credit prices, state subsidies, methods for estimating carbon
      sequestered, and harvesting of trees, we find great variation in the impact of
      the Grain for Green program on incomes and on carbon sequestered over a 48 year
      period at both the county and township levels.

PMID- 17178434
TI  - Stochastic resonance in two simple compare-and-fire models.
AB  - Two neural models are analysed and shown to exhibit the stochastic resonance
      effect. Namely, they respond to an underthreshold sinusoidal signal with an
      output signal whose signal-to-noise ratio (SNR) firstly increases then decreases
      as the intensity of noise affecting the system increases. The resonance curves
      are determined, analytically for the first and simplest model and by a synthetic
      method for the second one, and the respective resonant behaviours are illustrated
      and interpreted.

PMID- 17178435
TI  - Modeling the long-term leaching behavior of (137)Cs, (60)Co, and (152,154)Eu
      radionuclides from cement-clay matrices.
AB  - Leaching characteristics of some radionuclides that are commonly encountered in
      radioactive waste streams from immobilized waste matrices in different cement
      clay grouts have been assessed to investigate the influence of the clay additives
      on the leaching behavior of the solid waste matrices. The International Atomic
      Energy's Agency (IAEA) standard leach method has been employed to study the leach
      pattern of (137)Cs, (60)Co, and (152,154)Eu radionuclides immobilized in ordinary
      Portland cement (OPC), OPC-bentonite, and OPC-red clay grouts. The examination of
      the leaching data revealed that adding clays to OPC reduces the leach pattern as
      OPC-bentonite<OPC-red clay<OPC for all studied radionuclides. The controlling
      leaching mechanism has been found to be diffusion and the mean apparent diffusion
      coefficients and leachability indices have been calculated for the studied waste
      matrices. Simplified analytical models have been derived to predict the
      cumulative leach fraction (CLF) of radionuclides over the studied experimental
      period. These simplified research models could be used as a screening tool to
      assess the performance of the waste matrix under repository conditions.

PMID- 17178436
TI  - Pretreatment of anaerobic digestion effluent with ammonia stripping and biogas
      purification.
AB  - In this study, ammonia stripping was optimized for pretreating anaerobic
      digestion effluent from an anaerobic digestion plant, and the possibility of
      using CO(2) stripping and biogas injection for adjusting the pH of the effluent
      before and after the ammonia stripping process was also investigated. For ammonia
      stripping, the results showed that an overdose of calcium hydroxide, i.e.,
      27.5g/L wastewater, achieved higher ammonia, phosphorus, chemical oxygen demand,
      suspended solids, and turbidity removal efficiency. An air flow rate of 5L/min
      for 1L of wastewater was thought as suitable for engineering application. The pH
      of the anaerobic digestion effluent can be increased from about 7 to about 9 by
      CO(2) stripping, however which is insufficient for ammonia stripping. For 1L of
      wastewater treated after ammonia stripping, the pH can be neutralized to about 7
      from greater than 11 through biogas injection at 1L/min for less than 30min, and
      continuous injection does not decrease the pH. It was roughly estimated that
      43m(3) of biogas (CH(4):CO(2) approximately 60%:40%) produced daily could be
      purified to CH(4):CO(2) approximately 74%:26% by neutralizing the pH of the 5m(3)
      anaerobic digestion effluent pretreated by ammonia stripping.

PMID- 17178437
TI  - Cloning and characterization of zebrafish (Danio rerio) cyclin-dependent kinase
      5.
AB  - Cyclin-dependent kinase 5 (cdk5) is a ubiquitous protein activated by neuron
      specific activators, p35 and p39. Cdk5 regulates neuronal migration,
      differentiation, axonogenesis, synaptic transmission and apoptosis. However, its
      role in primary neurogenesis remains unexplored. Here, we have cloned and
      characterized the zebrafish cdk5 ortholog. Zebrafish cdk5 is 96% identical to its
      human counterpart. In situ hybridization analyses demonstrated that zebrafish
      cdk5 transcripts are ubiquitously expressed as early as the blastula stage. At
      11.5h of development, cdk5 transcripts were present in the neural plate at the
      domains where primary neurons begin to be specified. RT-PCR analyses showed equal
      levels of cdk5 transcripts up to 72 h of development. SiRNA-mediated cdk5
      knockdown resulted in a reduction in primary sensory neurons of the trigeminal
      ganglia of the peripheral nervous system, suggesting that cdk5 plays a crucial
      role in the development of the peripheral nervous system.

PMID- 17178438
TI  - Involvement of GDNF and its receptors in the maturation of the periodontal
      Ruffini endings.
AB  - Our recent study revealed an intense immunoreaction for GDNF and its receptors in
      the Ruffini endings, primary mechanoreceptors in the periodontal ligament, of
      young rats. However, no information is available for the expression of GDNF and
      its receptors during their development. The present study aimed to reveal
      postnatal changes in the immuno-expression of GDNF, GFRalpha1 and RET in the
      periodontal Ruffini endings of the rat incisors by double immunofluorescent
      staining. At postnatal day 3 (PO 3d), no structure with GDNF-, GFRalpha1-, or RET
      immunoreaction existed in the periodontal ligament. The PGP 9.5-positive nerve
      fibers without GDNF- and RET-immunoreaction displayed a dendritic fashion at PO
      1w, with a GFRalpha1-reaction found around these nerves. At PO 2w, GDNF-positive
      terminal Schwann cells occurred near the thick and dendritic axons, a part of
      which showed a RET-reaction, with no reactive cells near the thin nerves. The
      terminal Schwann cells became positive for GFRalpha1, but lacked RET
      immunoreaction. At PO 3w, when the formation of the periodontal Ruffini endings
      had proceeded, GDNF-positive terminal Schwann cells began to increase in number.
      This stage-specific immuno-expression pattern suggests that GDNF is a key
      molecule for the maturation and maintenance of the periodontal Ruffini endings.

PMID- 17178439
TI  - Infection of dogs by experimental inoculation with human isolates of Giardia
      duodenalis: clinical and laboratory manifestations.
AB  - The susceptibility of dogs to experimental inoculation with trophozoites and
      cysts of human isolates of Giardia duodenalis and the clinical and laboratory
      profiles of infection of these animals were studied. Two groups (A and B), each
      comprising three dogs, were inoculated with G. duodenalis trophozoites and cysts,
      respectively. A third group of two dogs was not inoculated and remained as
      control. After inoculation feces were collected daily to determine the pre-patent
      period, by flotation in 33% zinc sulfate solution. Blood samples (5mL) were
      collected from animals at 15-day intervals during the 165 days of the
      experimental period and were used to carry out the hemogram and biochemical
      evaluation of the levels of total protein, albumin, alanine aminotransferase,
      gamma glutamyltransferase, urea and creatinine. A prepatent period was observed
      at 5-6 days post-inoculation (p.i.) in the inoculated dogs, with cysts eliminated
      for approximately 3 months. No alterations were seen in the clinical parameters
      evaluated. Anemia was observed at 15 p.i. in the inoculated dogs. The mean
      eosinophil count of inoculated groups was higher than that of the control (p< or
      =0.05) but none of the biochemical parameters analyzed presented significant
      differences. The results of this study show that G. duodenalis from human
      isolates is able to infect dogs with minimal systemic manifestations without
      producing clinical signs of giardiasis.

PMID- 17178440
TI  - Detection of Babesia bigemina infection in strains of Rhipicephalus (Boophilus)
      microplus collected from outbreaks in south Texas.
AB  - The sudden death of several cattle infested experimentally with Rhipicephalus
      (Boophilus) microplus led to a clinical investigation into the reasons for the
      unexpected mortality. Microscopic evidence for Babesia bigemina infection was
      found in blood smears from the affected animals and a PCR assay was designed to
      detect the presence of B. bigemina and Babesia bovis in all R. microplus strains
      received and propagated at the laboratory. The assay utilizes a nested PCR
      approach with the first PCR amplifying a well-conserved segment from the Babesia
      18S ribosomal RNA gene followed by a nested PCR with Babesia species-specific
      primers and annealing temperatures enabling amplification of the 18S ribosomal
      RNA gene fragment specific to either B. bigemina or B. bovis. DNA from groups of
      50 larvae was extracted using a rapid DNA preparation protocol, which consisted
      of grinding the frozen tick larvae in PCR buffer and boiling the mixture for
      5min. The assay sensitivity allowed for the detection of the equivalent of a
      single infected tick larva. R. microplus eggs were also analyzed, but yolk
      protein viscosity created inconsistent results with the crush and boil DNA
      isolation protocol, necessitating the use of a more extensive proteinase K
      digestion-based DNA purification method. We detected the presence of B. bigemina
      in all strains of R. microplus currently reared at the laboratory and 4 of 26
      strains collected from infestation outbreaks in Texas by the U.S. Cattle Fever
      Tick Eradication Program.

PMID- 17178441
TI  - Use of quantitative real-time PCR to monitor the shedding and treatment of
      chlamydiae in the koala (Phascolarctos cinereus).
AB  - The aim of this study was to monitor chlamydial shedding patterns in clinically
      affected koalas before, during and following treatment using quantitative real
      time PCR. Swab samples were obtained from 14 koalas presented for treatment at
      the Australian Wildlife Hospital. Four of these animals were followed over a
      period of 8-9 weeks. Primers were designed based on the consensus signature
      sequence of the 16S rRNA chlamydial gene. Additional primers were designed based
      on the sequence of the koala beta-actin gene and used to normalize chlamydial
      values when comparing results from different swab samples. Chlamydial 16S rRNA
      gene copy number was highest in swab samples from clinically affected sites.
      Daily injections of chloramphenicol resulted in a marked and rapid reduction in
      the numbers of chlamydiae being shed from all sites. In general, chlamydial copy
      number was no longer detectable by the end of the 2nd week of treatment. No
      evidence of relapse of infection was detected at 2 weeks after the cessation of
      treatment. In contrast, topical chloramphenicol treatment of the eyes required a
      longer treatment period and had little effect on the shedding of chlamydiae from
      other sites of the body. Further studies are required to confirm the efficacy of
      a shorter treatment period.

PMID- 17178442
TI  - Prevalence of mycoplasmas in the semen and vaginal swabs of Danish stallions and
      mares.
AB  - The reproduction rate of horses is one of the lowest within domestic livestock
      despite advances the veterinary medicine. Infertility in horses may be due mainly
      to the lack of suitable selection criteria in the breeding of horses. However,
      acquired infertility due to genital, bacterial infections may occur. Mycoplasmas
      have been implicated in genital disorders and infertility of many species
      including humans and horses. However, their role as commensals or pathogens of
      the genital tract of horses is still not determined. Bacteriological examinations
      made on the fossa glandis, urethra, penis and semen of stallions, showed the
      presence of different Mycoplasma species. Therefore our study aimed to find the
      prevalence of Mycoplasma species and a possible association with fertility
      problems in Danish riding horses. Eighty semen samples from stallions and 19
      vaginal swab samples from mares were tested by PCR for presence of mycoplasmal
      DNA. The vaginal swab samples were also cultured in the Mycoplasma specific
      medium. None of the samples were positive for presence of genital mycoplasmas
      during the screen. The lack of genital mycoplasmas observed in this study may be
      due to a very extensive use of artificial insemination of modern sport horses.

PMID- 17178443
TI  - Effect of nicotine on in vitro maturation of bovine oocytes.
AB  - The putative effect of nicotine on maturation and the chromosomal complement of
      bovine oocytes were investigated in the present study. Cumulus-enclosed oocytes
      were incubated in maturation medium with 0, 0.5, 1.0, 2.5, 5.0, and 10.0 mmol
      concentrations of nicotine. The results indicated that: (1) nicotine affected
      cumulus cell expansion in a dose-dependent manner and the perivitelline space
      failed to form when concentrations were equal to or greater than 5.0 mmol; (2)
      oocytes treated with 0.5 and 1.0 mmol nicotine concentrations resulted in
      maturation rates (83.3% and 85.9%, respectively) which was similar to the control
      (86.2%), whereas treatment with 2.5 and 5.0 mmol concentrations significantly
      decreased maturation rates to 70.2% and 26.7%, respectively; (3) nicotine at or
      over 2.5 mmol caused extremely irregular meiotic spindles and interrupted
      microfilament organization; (4) chromosomal analyses of oocytes with PB1 showed
      that oocytes derived from 0.5 and 1.0 mmol nicotine groups had haploid
      complements similar to the control (87-90%), but when the concentrations were
      increased to 2.5 and 5.0 mmol the haploid state was significantly reduced to
      around 70%; (5) oocytes at GVBD (germinal vesicle breakdown) and metaphase I
      stages were less affected by nicotine at 5.0 and 10.0 mmol concentrations than GV
      stage oocytes; (6) maturation rates of the short-term nicotine-treated oocytes
      could be improved when subsequently incubated in normal maturation medium.
      Prolonged culture of nicotine-pretreated oocytes resulted in self-activation and
      some oocytes formed 1 or 2 pronuclei. In conclusion, nicotine affects bovine
      oocyte cumulus cell expansion, maturation rate, and chromosomal complement in a
      dose-dependent and an oocyte-stage-dependent manner.

PMID- 17178444
TI  - Parallel screening approach to identify solubility-enhancing formulations for
      improved bioavailability of a poorly water-soluble compound using milligram
      quantities of material.
AB  - In this article, we present a parallel experimentation approach to rapidly
      identify a solubility-enhancing formulation that improved the bioavailability of
      a poorly water-soluble compound using milligrams of material. The lead compound
      and a panel of excipients were dissolved in n-propanol and dispensed into the
      wells of a 96-well microtiter plate by a TECAN robot. Following solvent
      evaporation, the neat formulations were diluted with an aqueous buffer, and
      incubated for 24h. The solubilization capacity of the excipients for the compound
      at 24h (SC(24h)), was determined by HPLC, and compared with its solubility in the
      corresponding neat formulations determined by a bench-scale method. The ranking
      order of solubilization capacity of the five tested formulations for this
      compound by this microscreening assay is same as the ranking order of the
      compound solubility in the neat formulations. Several formulations that achieved
      the target aqueous solubility were identified using the screening method. One of
      the top formulations, an aqueous solution of the compound containing 20% Tween 80
      by weight, increased the compound solubility from less than 2 microg/mL to at
      least 10mg/mL. In a rat pharmacokinetic (PK) study, the Tween 80 formulation
      achieved 26.6% of bioavailability, a significant improvement over 3.4% of
      bioavailability for the aqueous Methocel formulation (p<0.01). The results in the
      study suggest that this parallel screening assay can be potentially used to
      rapidly identify solubility-enhancing formulations for an improved
      bioavailability of poorly water-soluble compounds using milligram quantities of
      material.

PMID- 17178445
TI  - Human oral drugs absorption is correlated to their in vitro uptake by brush
      border membrane vesicles.
AB  - Brush border membrane vesicles (BBMV) were prepared from the rabbit small
      intestine for testing drug absorption potency through the enterocyte's apical
      membrane, which is an important compartment for drug oral absorption. Some
      modifications have been made to the traditional vesicle assay for adapting it to
      the 96-well plate format. The accumulation of 23 reference drugs was measured,
      and the data showed a good correlation with human oral absorption with a
      correlation coefficient R=0.853 (P<0.001), with the exception of a few false
      positive results. As the measured drug absorption may contain a membrane/protein
      binding component as well as drug uptake into vesicles, these two fractions can
      be discriminated by changing extravesicular osmolarity using different mannitol
      concentrations. This model can be applied for evaluating drug absorption
      rate/mechanisms, and helping drug selection in early drug research and
      development.

PMID- 17178446
TI  - Preoperative evaluation of the congenital aural atresia on computed tomography;
      an analysis of the severity of the deformity of the middle ear and mastoid.
AB  - OBJECTIVE: To compare the development of temporal bone in normal and atretic ears
      and to assess some radiological landmarks that could be important in the hearing
      restoration interventions in such patients. MATERIAL AND METHODS: Thirty-five
      patients with 40 atretic external ears were evaluated with temporal bone CT and
      compared to a control group of 40 normal ears retrospectively. Using comparable
      slice levels in all patients, the course and the caliper of the facial canal, the
      surface area of the incus and malleus, the level of mastoid aeration, the
      location and anteroposterior diameters of the jugular bulb and sigmoid sinus, the
      direction and the caliber of the tympanic bony part of the Eustachian tube, area
      of the middle ear cavity, distance from facial nerve to incudomalleolar joint, to
      the vestibule and to the jugular bulb were included in the assessment. Non
      parametric and parametric statistical tests were used for comparison. RESULTS: In
      atretic ears middle ear sectional area was found to be smaller at the equivalent
      plane as compared to control subjects (mean area index: 19.3mm(2) versus
      47.4mm(2)). Mastoid aeration was low in general and the ossicles in the atretic
      ears were hypoplastic (mean ossicular sectional area: 8.3mm(2) versus 11 mm(2)).
      The distance from the jugular bulb to the facial nerve was significantly lower
      (mean: 6.2mm versus 6.8mm) (p<0.05) in the atretic ears. Facial canal caliber,
      distance from the facial canal to the incudomalleolar joint and distance from the
      facial canal to the vestibule in the atretic ears (means: 1.49, 2.93 and 1.82,
      respectively) did not show statistically significant difference from the control
      subjects (means: 1.44, 2.91 and 1.83, respectively) (p>0.05 for all). CONCLUSION:
      External ear atresia is significantly associated with middle ear and mastoid
      abnormalities. The ossicles were underdeveloped which always have to be
      considered during reconstructive surgery. Radiologically, in the atretic ears
      anterior-posterior length of the temporal bone was more influenced as compared to
      superior-inferior portion, which justifies abnormal route of the facial nerve
      canal. However, there is no abnormality in the development of the facial nerve as
      the caliper is similar to the control subjects.

PMID- 17178447
TI  - BI-RADS: use in the French radiologic community. How to overcome with some
      difficulties.
AB  - In the United States, BI-RADS (Breast Imaging Reporting and Data System) has been
      set up as a quality assurance system for better communication between
      professionals and for the follow-up of breast screening programs. It has become a
      reference in the field of mammographic imaging and has been adopted by several
      countries throughout the world. It has been translated in French. The aim of this
      article is to discuss the difficulties in using it in the French radiologic
      communities. There are few problems with vocabulary excepted for
      microcalcifications. BI-RADS includes a guidance chapter giving some
      recommendations for using properly the lexicon. Classification of normal breast
      remains of concern, as it is difficult to evaluate precisely the content of fat
      and as the final image is also dependant of technical factors. The main
      difficulties are related to final classification in BI-RADS categories as the
      lexicon does not explicit which mammographic features should be included in the
      categories from three to five. In France, a table concerning the classification
      of mammographic abnormalities has been established by the HAS (former ANAES)
      which represents the highest scientific health authority in France. There are no
      major problems for using the BI-RADS for US and MRI. BI-RADS is suitable for
      different categories of women and for male and training has an important impact
      on acceptance and proper use of the lexicon.

PMID- 17178448
TI  - Isolation and characterisation of a phenolic impurity in a commercial sample of
      duloxetine.
AB  - A phenolic impurity of duloxetine hydrochloride was isolated and characterised
      (MS, NMR, X-ray-analysis).

PMID- 17178449
TI  - Synthesis of biocompatible hydrophobic silica-gelatin nano-hybrid by sol-gel
      process.
AB  - Silica-biopolymer hybrid has been synthesised using colloidal silica as the
      precursor for silica and gelatin as the biopolymer counterpart. The surface
      modification of the hybrid material has been done with methyltrimethoxysilane
      leading to the formation of biocompatible hydrophobic silica-gelatin hybrid. Here
      we are reporting hydrophobic silica-gelatin hybrid and coating precursor for the
      first time. The hybrid gel has been evaluated for chemical modification, thermal
      degradation, hydrophobicity, particle size, transparency under the UV-visible
      region and morphology. FTIR spectroscopy has been used to verify the presence of
      CH(3) groups which introduce hydrophobicity to the SiO2-MTMS-gelatin hybrids. The
      hydrophobic property has also been tailored by varying the concentration of
      methyltrimethoxysilane. Contact angle by Wilhelmy plate method of transparent
      hydrophobic silica-gelatin coatings has been found to be as high as approximately
      95 degrees . Oxidation of the organic group which induces the hydrophobic
      character occurs at 530 degrees C which indicates that the surface hydrophobicity
      is retained up to that temperature. Optical transmittance of SiO2-MTMS-gelatin
      hybrid coatings on glass substrates has been found to be close to 100% which will
      enable the hybrid for possible optical applications and also for preparation of
      transparent biocompatible hydrophobic coatings on biological substrates such as
      leather.

PMID- 17178450
TI  - Protein release behavior from porous microparticle with lysozyme/hyaluronate
      ionic complex.
AB  - Porous microparticles (PMs) with a low density (<0.4 g/cm3) for pulmonary protein
      delivery were prepared by the water-in-oil-in-water (W1/O/W2) multi-emulsion
      method using a cyclodextrin derivative as a porogen. The complexation of
      positively charged lysozyme (Lys) and negative-charged hyaluronate (HA) was
      investigated for long-term protein release from PMs. The interaction of Lys and
      HA not only increased protein encapsulation efficiency but also stabilized Lys
      against a denaturing organic solvent (dichloromethane). Furthermore, PMs with
      Lys/HA complexes increased the Lys release period up to 7 days, as opposed to a
      4h Lys release time from PMs without Lys/HA complexes. In particular, PMs
      containing 10mg of HA and 50mg of Lys showed almost zero-order Lys release
      kinetic for 7 days and preserved the bioactivity of Lys more than 98% during its
      entire release period. This result suggests that PMs with Lys/HA complexes may be
      applied in long-term pulmonary administration of protein or peptide drugs,
      including those that require particles to arrive at a deep lung epithelium with
      the help of low density (high porosity) of PMs.

PMID- 17178451
TI  - Electrochemical determination of dipyridamole at a carbon paste electrode using
      cetyltrimethyl ammonium bromide as enhancing element.
AB  - Electrochemical behaviors of dipyridamole (DIP) at a carbon paste electrode in
      the presence of cetyltrimethyl ammonium bromide (CTAB) were investigated by
      voltammetry, chronocoulometry and electrochemical impedance spectroscopy (EIS).
      The results indicated that the electrochemical responses of DIP are apparently
      improved by CTAB, due to the enhanced accumulation of dipyridamole at the carbon
      paste electrode surface. Electrochemical parameters for the oxidation of DIP were
      explored by chronocoulometry. Under optimal conditions, the oxidation peak
      current at 0.53 V was proportional to DIP concentration in the range of 0.03-12
      microg mL-1, with a detection limit of 0.01 microg mL-1 for 120 s accumulation by
      different pulse voltammetry (DPV). This method was applied to the determination
      of DIP in the tablet samples. The results were satisfying compared with that
      obtained by standardized method of high performance liquid chromatography (HPLC).

PMID- 17178452
TI  - Thermosensitive polymer (N-isopropylacrylamide) coated nanomagnetic particles:
      preparation and characterization.
AB  - Thermosensitive polymer coated nanomagnetic adsorbents were synthesized by seed
      polymerization using surface modified nanomagnetic particles as the seeds. The
      Fe3O4 nanomagnetic particles were prepared by chemical precipitation of Fe2+ and
      Fe3+ salts in the ratio of 1:2 under alkaline and inert condition. The surface of
      these particles was modified by surfactants to achieve stability against
      agglomeration. These stable particles were then polymerized using N
      isopropylacrylamide (NIPAM) as the main monomer, methylene-bis-acrylamide as the
      crosslinker and potassium per sulfate as the initiator. The thermosensitive
      adsorbents were characterized by using transmission electron micrography (TEM)
      and vibrating sample magnetometer (VSM). TEM showed that the particle remained
      discrete with a mean diameter of 12 nm. Magnetic measurements revealed that the
      particles are superparamagnetic only with a decrease of magnetism after binding
      with the polymer due to the increase in surface spin disorientation. Pure Fe3O4
      spinel structure of these nanoparticles was indicated by the X-ray diffraction
      (XRD) patterns. The polymerization of NIPAM with the surface modified
      nanomagnetic particles was confirmed by Fourier transform spectroscopy (FTIR),
      Thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS). In
      addition, the adsorption/desorption of BSA molecule on these thermosensitive
      nanoparticles was investigated as a function of temperature. More than 60%
      desorption efficiency was achieved under appropriate condition.

PMID- 17178453
TI  - Keratin function in skin epithelia: a broadening palette with surprising shades.
AB  - Keratins make up the largest subgroup of intermediate filament (IF) proteins and
      form a dynamic network of 10-12 nm filaments, built from type I/type II
      heterodimers, in the cytoplasm of epithelial cells. A major function of keratin
      IFs is to protect epithelial cells from mechanical and non-mechanical stresses
      that cause cell rupture and death. Interference with this role is the root cause
      of a large number of inherited epithelial fragility conditions. Additional
      functions, non-mechanical in nature, are manifested in a way that depends on the
      specific keratin and on the epithelial context. The recent discovery of unusual
      mutations affecting keratin proteins has uncovered a novel dimension of their
      mechanical support function, and has synergized with mouse genetics to reveal a
      role in skin pigmentation. Other studies extended the role of keratin proteins in
      regulating the response to pro-apoptotic signals, and revealed their ability to
      modulate protein synthesis and cell size in epithelial cells challenged to grow.

PMID- 17178454
TI  - Gamma-tubulin complexes and microtubule organization.
AB  - Microtubule nucleation requires gamma-tubulin, which exists in two main protein
      complexes: the gamma-tubulin small complex, and the gamma-tubulin ring complex.
      During mitosis, these complexes accumulate at the centrosome to support spindle
      formation. Gamma-tubulin complexes are also present at non-centrosomal
      microtubule nucleation sites, both in interphase and in mitosis. In interphase,
      non-centrosomal nucleation enables the formation of microtubule bundles or
      networks of branched microtubules. Gamma-tubulin complexes may be involved not
      only in microtubule nucleation, but also in regulating microtubule dynamics.
      Recent findings indicate that the dynamics of microtubule plus-ends are altered,
      depending on the expression of gamma-tubulin complex proteins.

PMID- 17178455
TI  - Diversification and specialization of the bacterial cytoskeleton.
AB  - The past decade has witnessed the identification and characterization of
      bacterial homologs of the three major eukaryotic cytoskeletal families: actin,
      tubulin and intermediate filaments. These proteins play essential roles in
      organizing bacterial subcellular environments. Recently, the ParA/MinD
      superfamily has emerged as a new bacterial cytoskeletal class, and imaging
      studies hint at the existence of even more, as yet unidentified, cytoskeletal
      systems. Much as the cytoskeleton is used for different purposes in different
      eukaryotic cells, the specific identities, functions and regulatory mechanisms of
      cytoskeletal proteins can vary between different bacterial species. In addition,
      extensive cross-talk between bacterial cytoskeletal systems may represent an
      important mode of cytoskeletal regulation. These themes of diversity, species
      specificity and crosstalk are emerging as central properties of cytoskeletal
      biology.

PMID- 17178456
TI  - Detection of fungal spores using a generic surface plasmon resonance immunoassay.
AB  - This paper describes a biosensor-based method for detection of fungal spores
      using surface plasmon resonance (SPR). The approach involves the use of a mouse
      monoclonal antibody (Pst mAb8) and a SPR sensor for label-free detection of
      urediniospores from the model organism Puccinia striiformis f.sp. tritici (Pst).
      In the subtractive inhibition assay, urediniospores and Pst mAb8 were mixed,
      urediniospore-bound Pst mAb8 removed by centrifugation and the remaining Pst mAb8
      quantified using the SPR sensor. Assay conditions were optimised and a detection
      limit of 3.1 x 10(5)urediniospores/ml was achieved. Spiked Pst samples were
      further examined in a background of a related spore and it was found that Pst
      detection was possible in this mixture. This study represent the first use of SPR
      technology for fungal spore detection as well as the first report of a successful
      biosensor-based detection strategy for Pst.

PMID- 17178457
TI  - The multifaceted role of Notch in cancer.
AB  - The diverse roles that Notch signals play during the development and maintenance
      of normal tissues are recapitulated in different forms of cancer. Depending on
      the tumor type, Notch can variously promote or limit tumor growth through either
      cell autonomous or cell non-autonomous effects on differentiation, cellular
      metabolism, cell cycle progression, angiogenesis, and possibly self-renewal and
      immune function. Of particular interest, recent findings indicate that a high
      fraction of T-cell acute lymphoblastic leukemias and lymphomas have activating
      mutations in the Notch 1 receptor, and that Notch signaling might have a role in
      the maintenance of normal and malignant stem cells.

PMID- 17178458
TI  - SUDEP in the Netherlands: a retrospective study in a tertiary referral center.
AB  - OBJECTIVE: To evaluate risk factors for sudden and unexpected death in epilepsy
      (SUDEP) in a high-risk population, i.e. patients treated in a Dutch tertiary
      referral center for epilepsy. METHODS: All patients who died between January 1999
      and April 2004 while under treatment of the epilepsy center were identified.
      Based on clinical data, deaths were classified as definite, probable, possible or
      non-SUDEP. Potential risk factors were compared in SUDEP cases and non-SUDEP
      cases. RESULTS: SUDEP incidence was 1.24 per 1000 patient years. SUDEP patients
      died at a younger age than patients from the control group of non-SUDEP deaths
      with epilepsy and had an earlier onset of epilepsy. However, the frequently
      mentioned factors in previous studies, i.e. male sex, generalized tonic-clonic
      seizures, high seizure frequency, specific AEDs, polytherapy with several AEDs,
      mental retardation, psychiatric illness and psychotropic comedication, were not
      found to be correlated with SUDEP. CONCLUSIONS: Even in this high-risk population
      of patients with refractory epilepsy, treated in a tertiary referral center,
      SUDEP is not a frequently occurring phenomenon. Specific risk factors could not
      be identified within an already high-risk population.

PMID- 17178459
TI  - Getting to the heart of regeneration in zebrafish.
AB  - A scientific and clinical prerogative of the 21st century is to stimulate the
      regenerative ability of the human heart. While the mammalian heart shows little
      or no natural regeneration in response to injury, certain non-mammalian
      vertebrates possess an elevated capacity for cardiac regeneration. Adult
      zebrafish restore ventricular muscle removed by surgical resection, events that
      involve little or no scarring. Recent studies have begun to reveal cellular and
      molecular mechanisms of this regenerative process that have exciting implications
      for human cardiac biology and disease.

PMID- 17178460
TI  - Fibrolipoma of the median nerve.
AB  - Neural fibrolipoma or fibrolipomatous hamartoma is an uncommon benign tumor that
      usually arises in the median nerve. Fibrofatty tissue proliferates around the
      nerve and infiltrates the epineurium and perineurium. We report a case of
      fibrolipomatous hamartoma of the left median nerve in an 18-year-old woman. Our
      objective was to describe the pathognomonic magnetic resonance imaging features,
      whose presence obviates the need for a diagnostic biopsy.

PMID- 17178461
TI  - Rituximab in rheumatic diseases.

PMID- 17178462
TI  - Infection in a dish: high-throughput analyses of bacterial pathogenesis.
AB  - Diverse aspects of host-pathogen interactions have been studied using non
      mammalian hosts such as Dictyostelium discoideum, Caenorhabditis elegans,
      Drosophila melanogaster and Danio rerio for more than 20 years. Over the past two
      years, the use of these model hosts to dissect bacterial virulence mechanisms has
      been expanded to include the important human pathogens Vibrio cholerae and
      Yersinia pestis. Innovative approaches using these alternative hosts have also
      been developed, enabling the isolation of new antimicrobials through screening
      large libraries of compounds in a C. elegans Enterococcus faecalis infection
      model. Host proteins required by Mycobacterium and Listeria during their invasion
      and intracellular growth have been uncovered using high-throughput dsRNA screens
      in a Drosophila cell culture system, and immune evasion mechanisms deployed by
      Pseudomonas aeruginosa during its infection of flies have been identified.
      Together, these reports further illustrate the potential and relevance of these
      non-mammalian hosts for modelling many facets of bacterial infection in mammals.

PMID- 17178463
TI  - Large-scale recovery of C-phycocyanin from Spirulina platensis using expanded bed
      adsorption chromatography.
AB  - C-phycocyanin was purified on a large scale by a combination of expanded bed
      adsorption, anion-exchange chromatography and hydroxyapatite chromatography from
      inferior Spirulina platensis that cannot be used for human consumption. First,
      phycobiliproteins were extracted by a simple, scaleable method and then were
      recovered by Phenyl-Sepharose chromatography in an expanded bed column. The
      purity (the A(620)/A(280) ratio) of C-phycocyanin isolated with STREAMLINE column
      was up to 2.87, and the yield was as high as 31 mg/g of dried S. platensis. After
      the first step, we used conventional anion-exchange chromatography for the
      purification steps, with a yield of 7.7 mg/g of dried S. platensis at a purity
      greater than 3.2 and with an A(620)/A(650) index higher than 5.0. The fractions
      from anion-exchange chromatography with a level of purity that did not conform to
      the above standard were subjected to hydroxyapatite chromatography, with a C-PC
      yield of 4.45 mg/g of dried S. platensis with a purity greater than 3.2. The
      protein from both purification methods showed one absolute absorption peak at 620
      nm and a fluorescence maximum at 650 nm, which is consistent with the typical
      spectrum of C-phycocyanin. SDS-PAGE gave two bands corresponding to 21 and 18
      kDa. In-gel digestion and LC-ESI-MS showed that the protein is C-phycocyanin.

PMID- 17178464
TI  - Plant responses to UV radiation and links to pathogen resistance.
AB  - Increased incident ultraviolet (UV) radiation due to ozone depletion has
      heightened interest in plant responses to UV because solar UV wavelengths can
      reduce plant genome stability, growth, and productivity. These detrimental
      effects result from damage to cell components including nucleic acids, proteins,
      and membrane lipids. As obligate phototrophs, plants must counter the onslaught
      of cellular damage due to prolonged exposure to sunlight. They do so by
      attenuating the UV dose received through accumulation of UV-absorbing secondary
      metabolites, neutralizing reactive oxygen species produced by UV, monomerizing UV
      induced pyrimidine dimers by photoreactivation, extracting UV photoproducts from
      DNA via nucleotide excision repair, and perhaps transiently tolerating the
      presence of DNA lesions via replicative bypass of the damage. The signaling
      mechanisms controlling these responses suggest that UV exposure also may be
      beneficial to plants by increasing cellular immunity to pathogens. Indeed,
      pathogen resistance can be enhanced by UV treatment, and recent experiments
      suggest DNA damage and its processing may have a role.

PMID- 17178465
TI  - Roles of DNA polymerases in replication, repair, and recombination in eukaryotes.
AB  - The functioning of the eukaryotic genome depends on efficient and accurate DNA
      replication and repair. The process of replication is complicated by the ongoing
      decomposition of DNA and damage of the genome by endogenous and exogenous
      factors. DNA damage can alter base coding potential resulting in mutations, or
      block DNA replication, which can lead to double-strand breaks (DSB) and to
      subsequent chromosome loss. Replication is coordinated with DNA repair systems
      that operate in cells to remove or tolerate DNA lesions. DNA polymerases can
      serve as sensors in the cell cycle checkpoint pathways that delay cell division
      until damaged DNA is repaired and replication is completed. Eukaryotic DNA
      template-dependent DNA polymerases have different properties adapted to perform
      an amazingly wide spectrum of DNA transactions. In this review, we discuss the
      structure, the mechanism, and the evolutionary relationships of DNA polymerases
      and their possible functions in the replication of intact and damaged
      chromosomes, DNA damage repair, and recombination.

PMID- 17178466
TI  - Sub-second cellular dynamics: time-resolved electron microscopy and functional
      correlation.
AB  - Subcellular processes, from molecular events to organellar responses and cell
      movement, cover a broad scale in time and space. Clearly the extremes, such as
      ion channel activation are accessible only by electrophysiology, whereas numerous
      routine methods exist for relatively slow processes. However, many other
      processes, from a millisecond time scale on, can be "caught" only by methods
      providing appropriate time resolution. Fast freezing (cryofixation) is the method
      of choice in that case. In combination with follow-up methodologies appropriate
      for electron microscopic (EM) analysis, with all its variations, such
      technologies can also provide high spatial resolution. Such analyses may include,
      for example, freeze-fracturing for analyzing restructuring of membrane
      components, scanning EM and other standard EM techniques, as well as analytical
      EM analyses. The latter encompass energy-dispersive x-ray microanalysis and
      electron spectroscopic imaging, all applicable, for instance, to the second
      messenger, calcium. Most importantly, when conducted in parallel, such analyses
      can provide a structural background to the functional analyses, such as cyclic
      nucleotide formation or protein de- or rephosphorylation during cell stimulation.
      In sum, we discuss many examples of how it is practically possible to achieve
      strict function-structure correlations in the sub-second time range. We
      complement this review by discussing alternative methods currently available to
      analyze fast cellular phenomena occurring in the sub-second time range.

PMID- 17178468
TI  - Growth and division of peroxisomes.
AB  - Peroxisomes are ubiquitous subcellular organelles, which are highly dynamic and
      display large plasticity in response to cellular and environmental conditions.
      Novel proteins and pathways that mediate and control peroxisome formation,
      growth, and division continue to be discovered, and the cellular machineries that
      act together to regulate peroxisome number and size are under active
      investigation. Here, advances in the field of peroxisomal dynamics and
      proliferation in mammals and yeast are reviewed. The authors address the signals,
      conditions, and proteins that affect, regulate, and control the number and size
      of this essential organelle, especially the components involved in the division
      of peroxisomes. Special emphasis is on the function of dynamin-related proteins
      (DRPs), on Fis1, a putative adaptor for DRPs, on the role of the Pex11 family of
      peroxisomal membrane proteins, and the cytoskeleton.

PMID- 17178467
TI  - New insights into nucleolar architecture and activity.
AB  - The nucleolus is the most obvious and clearly differentiated nuclear
      subcompartment. It is where ribosome biogenesis takes place and has been the
      subject of research over many decades. In recent years progress in our
      understanding of ribosome biogenesis has been rapid and is accelerating. This
      review discusses current understanding of how the biochemical processes of
      ribosome biosynthesis relate to an observable nucleolar structure. Emerging
      evidence is also described that points to other, unconventional roles for the
      nucleolus, particularly in the biogenesis of other RNA-containing cellular
      machinery, and in stress sensing and the control of cellular activity. Striking
      recent observations show that the nucleolus and its components are highly
      dynamic, and that the steady state structure observed by microscopical methods
      must be interpreted as the product of these dynamic processes. We still do not
      have detailed enough information to understand fully the organization and
      regulation of the various processes taking place in the nucleolus. However, the
      present power of light and electron microscopy (EM) techniques means that a
      description of nucleolar processes at the molecular level is now achievable, and
      the time is ripe for such an effort.

PMID- 17178470
TI  - Regenerating the brain.

PMID- 17178471
TI  - Serotonin and brain: evolution, neuroplasticity, and homeostasis.

PMID- 17178472
TI  - Therapeutic approaches to promoting axonal regeneration in the adult mammalian
      spinal cord.

PMID- 17178473
TI  - Evidence for neuroprotective effects of antipsychotic drugs: implications for the
      pathophysiology and treatment of schizophrenia.

PMID- 17178474
TI  - Neurogenesis and neuroenhancement in the pathophysiology and treatment of bipolar
      disorder.

PMID- 17178475
TI  - Neuroreplacement, growth factor, and small molecule neurotrophic approaches for
      treating Parkinson's disease.

PMID- 17178476
TI  - Using Caenorhabditis elegans models of neurodegenerative disease to identify
      neuroprotective strategies.

PMID- 17178477
TI  - Neuroprotection and enhancement of neurite outgrowth with small molecular weight
      compounds from screens of chemical libraries.

PMID- 17178479
TI  - Reconstruction of full-thickness cheek defects with combined temporalis myofacial
      and facial-cervico-pectoral flaps.
AB  - OBJECTIVE: The objective of this study was to assess using the temporal myofacial
      flaps (TMFF) and the facial-cervico-pectoral flap (FCPF) to provide both inner
      and outer linings for large full-thickness cheek defects following ablative oral
      cancer surgery. STUDY DESIGN: Twelve patients with malignant tumors in the buccal
      region were treated by extensive surgical dissection, and the cheek mucosa
      defects were repaired with the TMFF and the cheek skin defects were reconstructed
      with the FCPF. There were 9 male and 3 female patients, age range from 18 to 70
      years (mean 52.8). The full-thickness cheek defects ranged from 7 x 6 cm to 10 x
      8 cm in size. RESULTS: No patient had complete loss of flap; 3 patients had minor
      complications (TMFF and FCPF partial necrosis and FCPF distal dehiscence) all of
      which settled with conservative management. Mouth opening was normal in 10
      patients, and facial contour was satisfactory in 8 patients. The follow-up period
      varied from 6 to 26 months (mean 15.2); 3 tumors had local recurrences and 2
      patients died from tumor metastasis. CONCLUSION: We found the technique to be
      anatomically sound, technically easy and reliable, and believe it is a useful
      method for the reconstruction of large full-thickness cheek defects.

PMID- 17178478
TI  - Orbital abscess from an odontogenic infection.
AB  - An orbital abscess is a rare but serious complication of an odontogenic
      infection, which can lead to loss of vision or worse. This paper presents a case
      of orbital abscess secondary to an infection from the upper molar teeth, which
      extended to the retobulbar and posterosuperior region of the orbit, close to the
      superior orbital fissure. The infection spreaded to the pterygopalatine and
      infratemporal fossa and then to the orbit via the inferior orbital fissure. This
      paper reviews the clinical presentation, differential diagnosis, route of spread,
      value of serial CT scanning, treatment and possible complications.

PMID- 17178480
TI  - Obturator after marsupialization of a recurrence of a radicular cyst of the
      mandible.
AB  - The radicular cyst is the most common odontogenic cyst. We present the case of a
      51-year-old man with an extended recurrence of a radicular cyst of the mandible
      that was treated with marsupialization. Subsequently, an obturator was fitted,
      and in 10 months a resolution (clinically and radiographically) of the cystic
      cavity was noticed without any signs of recurrence. The marsupialization is a
      well-established, nonaggressive treatment of large odontogenic cysts and shows
      advantages in preserving vital structures, with reduced risk of pathological
      mandibular fractures. The patient, however, must be compliant and accept the
      prolonged treatment of marsupialization.

PMID- 17178481
TI  - Short root anomaly associated with Rothmund-Thomson syndrome.
AB  - A case of short root anomaly in a patient with Rothmund-Thomson syndrome is
      reported. The syndrome is a rare genodermatosis characterized by poikilodermatous
      rash starting in infancy, associated with juvenile cataracts, small stature,
      skeletal abnormalities, dental malformations, and predisposition to skin and bone
      cancers. In this case, abnormally short roots were detected during radiographic
      examination, affecting a complete permanent dentition including partially erupted
      third molars. The report contains a short review of the current literature on
      Rothmund-Thomson syndrome.

PMID- 17178482
TI  - Relationship between magnetic resonance imaging and histopathologic findings in
      thrombosis in the oral and maxillofacial region: a case report.
AB  - Histopathologic changes are observed during the clinical course of thrombosis,
      and the evaluation of such changes by magnetic resonance imaging (MRI) might
      enhance the accuracy of qualitative diagnosis of the disease. The relationship
      between histopathologic and MRI findings in the chronic phase of deep venous
      thrombosis (DVT) that developed in the masseter muscle of a 50-year-old Japanese
      female patient is described. Two regions with different MRI signal intensities
      were identified, and a 3-layer structure was observed by microscopy. The distinct
      MRI regions correlated with the microscopic structure, suggesting that MRI can be
      used for qualitative imaging of a maxillofacial thrombus.

PMID- 17178484
TI  - A case of tularemia presenting as a dental abscess: case report.
AB  - OBJECTIVE: The purpose of this report is to present a tularemia case accompanied
      by a neck mass that easily may be confounded with dental abscess. SUMMARY:
      Francisella tularensis is a potential agent of biologic terrorism. Thirty percent
      of the symptoms seen in tularemia localize in the head and neck region and are
      sometimes mistaken for complications of a dental abscess. To our knowledge,
      reports of the differential diagnostic characteristics of tularemia are lacking
      in the dental literature and, to date, no dental journal articles have focused on
      the disease. In this present case, a 51-year-old woman arrived at the public
      health department with high fever and facial swelling. The findings suggested a
      dental origin and the patient was directed to dentistry. Radiology and a detailed
      intraoral and extraoral examination failed to reveal a dental problem.
      Fortunately, the patient was known to come from a tularemia region; with the
      suspicion of tularemia the patient was referred to the faculty of medicine.
      Serologic tests showed that the patient had a Francisella tularensis infection.

PMID- 17178483
TI  - A comparison of 5 gutta-percha obturation techniques to replicate canal defects.
AB  - OBJECTIVE: The purpose of this study was to compare the ability of five different
      methods of compaction of thermoplasticized GP to replicate four artificially
      created defects in the canal walls of an extracted tooth. One of the instruments
      tested was the EndoTwinn which was recently introduced to the U.S. market and can
      be used in both the warm lateral (WLC) and warm vertical compaction (WVC)
      techniques. STUDY DESIGN: Four artificially-created defects were created in the
      dentinal walls of a split-tooth model which could be separated after each
      obturation and the obturation mass removed for visual evaluation. Twenty
      obturations were evaluated for each of the following techniques: Group 1, WLC
      without vibration using the EndoTwinn; Group 2, WLC with heat and vibration using
      the EndoTwinn; Group 3, WVC using the Elements Obturation System (EOS); Group 4,
      Injectable GP using the EOS; and Group 5, WVC using the EndoTwinn. Kruskal-Wallis
      statistic was used to determine statistically significant differences, pairwise
      comparisons were analyzed with the Mann Whitney statistic and a Bonferonni
      adjustment was made, where indicated. RESULTS: Nonparametric analyses with
      appropriate Bonferroni adjustments indicated statistically significant results
      favoring Groups 2 and 4. CONCLUSIONS: The EndoTwinn, in heat and vibration mode,
      and the EOS resulted in better replication of the defects than the other
      techniques.

PMID- 17178486
TI  - Race headlining case reports - why?

PMID- 17178485
TI  - Comparison of methylprednisolone and ketoprofen after multiple third molar
      extraction: a randomized controlled study.
AB  - In a prospective, double blind, and randomized study, we compared
      methylprednisolone and ketoprofen after anesthesia for multiple third molar
      extraction. In addition to paracetamol, 90 patients were allocated to receive
      intravenously either ketoprofen 100 mg or methylprednisolone 1 mg/kg. Severity of
      pain was measured with visual analogue scale (VAS) in recovery room. Sixty-three
      percent of patients receiving methylprednisolone had a VAS score <30 mm compared
      with 42% of those receiving ketoprofen (P = 0.04), with no difference in the
      consumption of morphine. We observed only marginal difference between
      methylprednisolone and ketoprofen to relieve pain after this surgery.

PMID- 17178487
TI  - Asymptomatic expansile lesion of the posterior mandible.

PMID- 17178488
TI  - Effect estimates and methodological quality of randomized controlled trials about
      prevention of alveolar osteitis following tooth extraction: a systematic review.
AB  - OBJECTIVE: To systematically review the scientific evidence derived from
      randomized controlled trials (RCT) about prevention of alveolar osteitis (AO).
      STUDY DESIGN: Literature searches were conducted to locate RCTs about prevention
      of AO. The RCTs were scrutinized for methodological details and categorized
      according to the preventive intervention studied. Data were analyzed in relation
      to the frequency of AO. Absolute risk reductions (ARR), and numbers needed to
      treat were calculated with 95% confidence limits. RESULTS: There was a wide
      variation in the design and quality of the RCTs (N = 32). The greatest risk
      reduction for AO was seen for local treatment with tetracycline (ARR, 12%-31%).
      For a majority of the preventive interventions, the evidence was absent or
      inconclusive. CONCLUSIONS: Local treatment with tetracycline, and also 0.12%
      chlorhexidine rinsing preoperatively and 7 days postoperatively, seem to have
      significant and clinically relevant preventive effect on AO following surgical
      removal of lower third molars.

PMID- 17178489
TI  - Expression of bone morphogenetic protein 2 and fibroblast growth factor 2 during
      bone regeneration using different implant materials as an onlay bone graft in
      rabbit mandibles.
AB  - OBJECTIVES: The purpose of this study was to histologically and
      immunohistochemically evaluate bone regeneration using 3 different implant
      materials in rabbit mandibles and to compare the bone regenerative capability of
      these materials in an animal model. STUDY DESIGN: Adult male Japanese white
      rabbits (n = 48; 12-16 wks old; 2.5-3.0 kg) were divided into 4 groups,
      consisting of 12 animals each. The implant materials were beta-tricalcium
      phosphate (beta-TCP), autologous bone derived from the radius, and recombinant
      human bone morphogenetic protein 2 (rhBMP-2) with polylactic acid/polyglycolic
      acid copolymer and gelatin sponge (PGS) complex. After incising along the
      inferior border of the mandible, the materials were implanted as only grafts and
      covered by titanium mesh with screws. No material was implanted into the control
      group. The rabbits were killed at 2, 4, 8, 12, and 24 wks postoperatively, and
      formalin-fixed specimens containing titanium mesh were embedded in acrylic resin.
      The specimens were stained with hematoxylin and eosin. For immunohistochemical
      analysis, the specimens were treated with BMP-2 and fibroblast growth factor 2
      (FGF-2) antibodies. Finally, they were examined microscopically. RESULTS: The
      autologous bone induced substantially more new bone formation compared with beta
      TCP at 4 wks postoperatively. However, rhBMP-2/PGS induced new bone formation at
      8 wks postoperatively. No growth of bony tissue was observed in the control group
      at any period. In the autologous bone and rhBMP-2/PGS groups, both BMP-2 and FGF
      2 were observed later in the beta-TCP group than in other groups. CONCLUSION:
      This study suggests that autologous bone as well as rhBMP-2/PGS implants induce
      expression of both BMP-2 and FGF-2 specifically at the operated sites, even at
      early stages.

PMID- 17178490
TI  - High condylectomy and disc repositioning compared to arthroscopic lysis, lavage,
      and capsular stretch for the treatment of chronic closed lock of the
      temporomandibular joint.
AB  - OBJECTIVE: The article shows the 1-yr results comparing the efficacy of open
      surgery high condylectomy and disc repositioning and the arthroscopic procedure
      of lysis, lavage and capsular stretch in patients with chronic closed lock of the
      temporomandibular joint (TMJ). STUDY DESIGN: Twenty patients with a clinical and
      radiologic diagnosis of chronic closed lock were randomly chosen to be treated
      with either open surgery or arthroscopy. Each patient was evaluated with a visual
      analog scale (VAS) for pain and a mandibular functional impairment questionnaire
      (MFIQ). The evaluation also included a clinical examination. Each patient was
      recorded at baseline before surgery and at 1-yr follow-up. Statistical analysis
      was made to evaluate whether differences in MFIQ, VAS, maximum opening and
      protrusion, lateral joint tenderness, muscle tenderness, crepitation, and
      clicking at 1-yr follow-up from baseline were significant. Results were
      considered statistically significant when P < .05. RESULTS: Both open surgery and
      arthroscopic surgery reduced pain and improved mandibular function. The severity
      of pain was significantly reduced in both groups (P = .005). In both the open and
      arthroscopy groups mandibular function improved significantly (P = .005). The
      clinical examination showed similar good results for the 2 surgical procedures.
      At 1-yr follow-up a majority of patients from both the open (80% of the patients)
      and the arthroscopy (70% of the patients) groups fulfilled the criterion of a
      cutoff point for maximum interincisal opening of equal or more than 35 mm (P =
      0.005); all the patients in both groups fulfilled the criterion of the cutoff
      point for maximum protrusion of more than 5 mm (P = .007). At 1-yr follow-up,
      clicking was the same as before surgical procedures; no patient in the open group
      showed crepitation, but crepitation was found in patients in the arthroscopy
      group. Joint tenderness and pain on lateral palpation as well as muscle
      tenderness and pain were reduced in all the cases, disappearing in some of them,
      but the difference was significant only regarding joint tenderness (open surgery,
      P = .016; arthroscopy, P = .031). CONCLUSIONS: Open-surgery high condylectomy and
      disc repositioning and the arthroscopic procedure of lysis, lavage and capsular
      stretch are both effective surgical methods to treat symptomatic patients with a
      diagnosis of chronic closed lock of the TMJ. Because of the minimally invasive
      character of the arthroscopic procedure, it should be considered as the first
      choice in the surgical treatment of the TMJ.

PMID- 17178491
TI  - Treatment of experimental peri-implantitis using autogenous bone grafts and
      platelet-enriched fibrin glue in dogs.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of autogenous
      bone grafts and platelet-enriched fibrin glue in the treatment of peri
      implantitis. STUDY DESIGN: Thirty-six screw-type commercially pure titanium
      implants with rough acid-etched surfaces were inserted into 6 mongrel dogs 3
      months after extraction of mandibular premolars. After 3 months of healing, peri
      implantitis was induced by placing gauze and wire around the implants. Once peri
      implantitis was created, surgical treatments involving a combination of
      autogenous bone grafts and platelet-enriched fibrin glue, autogenous bone grafts
      alone, or a conventional flap procedure only (control) were carried out. Six
      months later, biopsies of the implant sites were taken and prepared for ground
      sectioning and analysis. RESULTS: The amount of reosseointegration was
      significantly higher in peri-implantitis defects treated with combined autogenous
      bone grafts and platelet-enriched fibrin glue as compared with the other 2
      treatment procedures. A mean bone-to-implant contact of 50.1% was obtained in the
      peri-implantitis lesions treated with combined autogenous bone grafts and
      platelet-enriched fibrin glue. The corresponding values for the autogenous bone
      grafts and control groups were 19.3% and 6.5%, respectively. CONCLUSION: The
      present study demonstrates that surgical treatment involving the combined use of
      autogenous bone grafts and platelet-enriched fibrin glue might effectively
      promote reosseointegration in lesions resulting from peri-implantitis.

PMID- 17178492
TI  - Infection following treatment of mandible fractures: the role of
      immunosuppression and polysubstance abuse.
AB  - OBJECTIVE: There is little data available on the relationship between
      immunosuppression and polysubstance abuse and postoperative infection in patients
      with mandibular fractures. In this study we aimed to assess these parameters.
      STUDY DESIGN: This study sample consisted of 120 patients who were admitted to
      the Department of Oral and Maxillofacial Surgery at the Washington Hospital
      Center between January of 1999 and February of 2002. Patient charts were reviewed
      and data regarding fracture location, mode of treatment, type of antibiotic
      therapy, and outcome of treatment including postoperative complications were also
      recorded. Patient's medical and social histories were also reviewed for a history
      of diabetes mellitus (DM), human immunodeficiency virus (HIV) status, alcohol
      abuse, and intravenous drug abuse (IVDA). RESULTS: Of the 120 patients in this
      study, 17 (14.1%) patients were identified as having a postoperative infection.
      Among those with postoperative infections, 8 (6.7%) had history of
      immunosuppression or polysubstance abuse. The strongest association found in this
      review is the relationship between alcohol (P = 0.50) and IVDA (P = 0.68), and
      the development of post-operative infections. There was also an increased rate of
      postoperative infection in HIV-positive patients (P = 0.71) and DM patients (P =
      0.77). CONCLUSION: In our study, we observed an increased risk for post-operative
      infection in HIV-positive individuals and diabetics. This finding lends support
      to other studies, which have shown a higher incidence of infection in HIV
      positive individuals. We also observed an increased risk for postoperative
      infection among patients with history of alcohol and drug abuse. Therefore, in
      treatment planning for the correction of mandible fractures in patients with
      histories of substance abuse, it seems appropriate to make efforts to decrease
      the postoperative risk.

PMID- 17178493
TI  - White sponge nevus: report of a three-generation family.
AB  - OBJECTIVE: White sponge nevus (WSN) is a rare autosomal dominant disorder that
      results in soft, white, and spongy plaques in the oral mucosa. The aim of this
      study was to describe the clinical, histopathologic, and genetic features of a
      family, spanning 3 generations, affected by WSN. STUDY DESIGN: This study was
      performed using a cross-sectional layout analyzing a family with WSN. RESULTS:
      Clinical examination of family members revealed that of 23 descendants, 8
      (34.78%) had WSN features. Unaffected and affected members transmitted the
      disease to their offspring. The offspring recurrence risk was 0.34, and an
      incomplete level of penetrance was observed. The lesions showed many clinical and
      histopathologic similarities to cases previously reported. The most affected
      sites were buccal and labial mucosa, with a rare appearance in the palate. No
      extraoral lesion was found. Histological examination showed intense acanthosis
      and hyperparakeratosis-induced epithelial hyperplasia. Within the spinous layer,
      cells showing perinuclear eosinophilic condensation of the cytokeratin (CK)
      filaments were frequent. CONCLUSION: The disease was transmitted by an autosomal
      dominant mode of inheritance, appearing mainly in the buccal and labial mucosa.

PMID- 17178494
TI  - Relationship between mucositis and changes in oral microflora during cancer
      chemotherapy.
AB  - It is thought that the incidence and severity of cancer chemotherapy-associated
      mucositis is caused in part by changes in the oral bacterial microflora. This
      systematic review examined the role of oral bacterial microflora changes in the
      development of oral mucositis during chemotherapy. Thirteen prospective clinical
      trials were identified, involving 300 patients with 13 different cancer
      diagnoses. There was great variability in patient populations, bacterial sample
      collection methodology, and oral sample sites. No clear pattern regarding
      qualitative and quantitative oral flora changes emerged among these studies. The
      most frequent Gram-negative species isolated during chemotherapy were from the
      Enterobacteriaceae family, Pseudomonas sp. and E. coli. The most common Gram
      positive species isolated were Staphylococcus sp. and Streptococcus sp. Five
      studies assessed the role of oral flora changes in the genesis of oral mucosal
      changes, with no consensus among them. More detailed studies are required to
      understand the relationship between chemotherapy, alterations in the nature and
      magnitude of the oral microflora, and the presence of mucositis.

PMID- 17178495
TI  - Signs of bruxism and temporomandibular disorders among psychiatric patients.
AB  - OBJECTIVES: To investigate the prevalence of bruxism and signs of
      temporomandibular disorders (TMDs) among psychiatric patients compared with a
      healthy population and to assess the effect of psychiatric medications on the
      parameters studied. STUDY DESIGN: Subjects included 77 psychiatric patients under
      treatment at 2 psychiatric hospitals in Israel and 50 healthy individuals
      (control). One experienced calibrated examiner performed the clinical examination
      (presence of bruxism and signs of TMD). RESULTS: Abnormal attrition was evident
      in 46.8% of the psychiatric patients compared with 20% in the controls (P <
      .005). Significant differences between groups were apparent for mean muscle
      sensitivity to palpation, joint sensitivity to palpation, and range of mouth
      opening. There were no differences between groups in the prevalence of joint
      clicks and no association between time of receiving treatment with dopamine
      antagonists (or any other psychotropic drugs) and TMD signs and symptoms.
      CONCLUSION: The higher prevalence of bruxism and signs of TMD in psychiatric
      patients is a major clinical comorbidity. Whether it is a manifestation of the
      abnormal central nervous system of psychiatric patients or neuroleptic-induced
      phenomenon deserves further attention. The exact factors that affect the pain
      experience in these patients should be evaluated as well.

PMID- 17178496
TI  - A random clinical trial study to assess the efficiency of topical applications of
      podophyllin resin (25%) versus podophyllin resin (25%) together with acyclovir
      cream (5%) in the treatment of oral hairy leukoplakia.
AB  - OBJECTIVE: The objective of this study was to assess the efficiency of topical
      applications of podophyllin resin (25%) (P) versus podophyllin resin (25%)
      together with acyclovir cream (5%) (PA) in the treatment of oral hairy
      leukoplakia (OHL) in accordance with the following criteria: (1) number of
      applications necessary for the total clinical resolution of OHL; (2) correlation
      between the decrease of lesion size and the number of applications; (3) total
      clinical resolution of OHL; and (4) clinical reevaluation 12 months after the end
      of treatment. STUDY DESIGN: Forty-six OHLs were treated with P (P group) or with
      PA (PA group). Applications were performed weekly. Student t, Fisher exact, and
      Pearson correlation tests were used for statistical analysis. RESULTS: All 24
      lesions from the PA group presented total clinical resolution while 4 lesions
      from the P group did not. The P group required up to 25 applications performed
      weekly while the PA group required up to 18. Observed was a negative significant
      association between the size of the lesions and the number of applications
      performed weekly in the PA group. CONCLUSIONS: The present study demonstrated the
      following: (1) P and PA topical treatments presented a similar average number of
      applications performed weekly; (2) both groups showed the same clinical response
      at 12 months post-therapy; and (3) PA presented a 100% clinical resolution and a
      continuous decrease in OHL size over the course of weekly applications.

PMID- 17178497
TI  - Ameloblastic carcinoma ex ameloblastoma: report of a case-possible involvement of
      CpG island hypermethylation of the p16 gene in malignant transformation.
AB  - Ameloblastic carcinoma is described in the updated World Health Organization
      (WHO) classification as a rare malignant lesion. Ameloblastic carcinoma meeting
      the WHO criteria may arise either as a result of malignant change in a pre
      existing benign ameloblastoma (carcinoma ex ameloblastoma) or as a primary
      malignant ameloblastoma not preceded by an ordinary ameloblastoma (de novo
      carcinoma). We report a case of ameloblastic carcinoma ex ameloblastoma and
      examine how this case underwent malignant transformation. The DNA was extracted
      separately from benign and malignant areas in paraffin sections of the tumor.
      Direct sequencing showed no genetic mutation of exons 5-8 of the p53 gene.
      Hypermethylation of CpG islands of the p16 gene was detected in the malignant
      parts of the tumor. The results indicate that hypermethylation of p16 may have
      been involved in the malignant transformation of the ameloblastoma in the present
      case.

PMID- 17178498
TI  - Basal cell adenocarcinoma of the oral minor salivary glands: review of the
      literature and presentation of two cases.
AB  - Basal cell adenocarcinoma (BCA) is an unusual salivary gland malignancy that very
      rarely affects the minor glands. Here we present 2 cases of BCA arising in the
      minor salivary glands of the left cheek and junction of the hard and soft palate,
      respectively. The patients were both women aged 66 and 42 years. The tumors
      assumed a tubular-trabecular and a solid-membranous pattern, respectively. Both
      tumors showed immunopositivity for S-100, Bcl-2, and cytokeratin 7. One tumor was
      also immunopositive for epithelial membrane antigen and carcinoembryonic antigen,
      and the other tumor was reactive with p53 and vimentin. Both tumors were
      surgically removed. A comprehensive literature review revealed only 21 previously
      reported cases of BCA of oral minor salivary glands. This is an exceptionally
      rare salivary gland tumor, which, despite its low-grade behavior, demands
      complete surgical removal with adequate margins. Immunohistochemical studies may
      complement a thorough histopathologic analysis in discriminating BCA from other
      salivary gland tumors.

PMID- 17178499
TI  - Gingival swelling in a 13-year-old girl with multiple recurrences.
AB  - We present a challenging case of gingival swelling that recurred several times in
      3.5 years in a 13-year-old girl. Histologic evaluation of the initial biopsy
      revealed groups of epithelioid cells surrounded by lymphocytes in the submucosal
      fibrous connective tissue, and it was diagnosed as noncaseating granulomatous
      inflammation. With the tissue specimens from subsequent multiple excisions and
      several immunohistochemical studies, the diagnoses evolved to benign cellular
      infiltrate of undetermined origin, epithelioid hemangioma, proliferating
      endothelial cell neoplasm of uncertain biologic potential, atypical vascular
      tumor, epithelioid hemangioendothelioma, and kaposiform hemangioendothelioma. We
      discuss the list of differential diagnoses from various pathologists and propose
      our diagnosis of epithelioid hemangioendothelioma based on its clinical behavior,
      histologic features, and immunohistochemical findings.

PMID- 17178500
TI  - Oral myiasis: a case report and literature review.
AB  - Myiasis is the infestation of tissues and organs of animals and humans by certain
      Dipteran fly larvae. This phenomenon is well documented in the skin, especially
      among animals and people in tropical and subtropical areas. Oral myiasis is a
      rare condition and can be caused by several species of Dipteran fly larvae and
      may be secondary to serious medical conditions. Upon removal of the larvae, the
      tissues seem to recover with no subsequent complications and with no need for
      further treatment. Here we describe a case of oral myiasis within the gingiva of
      a healthy young man caused by the larvae of Wohlfahrtia magnifica (Family
      Sarcophagidae), in which infection may have been due to ingestion of infested
      flesh. Reviewing the literature revealed that most cases of oral myiasis tend to
      be multiple and to occur in anterior segments of the jaws rather than in
      posterior segments as in the case we describe here.

PMID- 17178501
TI  - Investigation of the beta-catenin gene in a case of dentinogenic ghost cell
      tumor.
AB  - Dentinogenic ghost cell tumor (DGCT) is considered as a neoplastic counterpart of
      the calcifying odontogenic cyst (COC). beta-catenin mutations have been described
      in COC suggesting a critical role in its histogenesis. In this study, we report a
      patient with DGCT contains a missense mutation on codon 3 (ACT --> TCT) of beta
      catenin gene. Immunohistochemistry showed nuclear, cytoplasmic, and membranous
      accumulation of beta-catenin in the tumor cells. TUNEL assay showed positive
      signals in nucleated cells adjacent to the ghost cells. Our data suggest that
      beta-catenin plays an important role in the tumorigenesis of DGCT. DGCT may
      develop by an improper differentiation process coordinated by Wnt signaling
      pathway. Further studies are needed to determine the genotypic/phenotypic
      characteristics of ghost cell-containing odontogenic lesions.

PMID- 17178502
TI  - Evaluation of cross-section airway configuration of obstructive sleep apnea.
AB  - Upper airway imaging techniques can be useful to identify the exact location and
      nature of the obstruction in obstructive sleep apnea (OSA) patients. Ten OSA
      patients and 10 non-OSA control subjects were imaged using cone-beam computed
      tomography (NewTom QR-DVT9000) to compare their upper airway structure. The OSA
      subjects presented higher BMI (OSA: 29.5 +/- 9.05 kg/m(2); non-OSA: 23.1 +/- 3.05
      kg/m(2) [P = .034]), lower total volume (mm(3)) of the airway (OSA: 4868.4 +/-
      1863.9; non-OSA: 6051.7 +/- 1756.4 [P = .054]), statistically significantly
      smaller anterior-posterior dimension (mm) of the minimum cross-section segment
      (OSA: 4.6 +/- 1.2; non-OSA: 7.8 +/- 3.31 [P = .009]), and smaller minimum cross
      section area (OSA: 45.8+/-17.5 mm(2); non-OSA: 146.9 +/- 111.7 mm(2) [P = .011])
      positioned below the occlusal plane in 70% of the cases (OSA:7 out of 10; non
      OSA: 5 out of 10 [P = .030]). The OSA group presented a concave or elliptic
      shaped airway and the non-OSA group presented a concave, round, or square shaped
      airway.

PMID- 17178503
TI  - Detection of cavitated carious lesions in approximal tooth surfaces by ultrasonic
      caries detector.
AB  - OBJECTIVE: A new diagnostic method for detecting cavitated carious lesions in
      approximal surfaces with the aid of an ultrasonic caries detector (UCD) was
      tested for clinical use. The objective of this study was to evaluate the efficacy
      and clinical performance of the UCD system and to compare it with bite-wing
      radiography by using direct visual inspection during restoration preparation as a
      validation method. STUDY DESIGN: One hundred ninety-seven directly inspected
      approximal sites, 95 as cavitated carious lesions and 102 as intact sites, of
      adults 22 to 45 years of age were examined by UCD and radiography. RESULTS:
      Ultrasonic caries detector sensitivity was 0.82 compared with 0.75 for bite-wing
      radiographs when the threshold was determined as radiolucency in inner enamel and
      dentin, and 0.49 when the threshold of radiolucency was in dentin. The
      specificity of UCD was 0.75 versus 0.9 for radiographs. CONCLUSIONS: The UCD
      exhibited a higher sensitivity than the radiographs but a lower specificity. This
      study presents a new diagnostic tool that can reduce patient exposure to ionizing
      radiation and improve caries detection.

PMID- 17178504
TI  - Limited cone-beam CT and intraoral radiography for the diagnosis of periapical
      pathology.
AB  - OBJECTIVE: To compare intraoral periapical radiography with 3D images for the
      diagnosis of periapical pathology. STUDY DESIGN: Maxillary molars and premolars
      and mandibular molars with endodontic problems and examined with periapical
      radiographs and a 3D technique (3D Accuitomo) were retrospectively selected and
      evaluated by 3 oral radiologists. Numbers of roots and root canals, presence and
      location of periapical lesions, and their relation to neighboring structures were
      studied. RESULTS: Among 46 teeth, both techniques demonstrated lesions in 32
      teeth, and an additional 10 teeth were found in the Accuitomo images. As regards
      individual roots, 53 lesions were found in both techniques, and 33 more roots
      were found to have lesions in Accuitomo images. Artefacts were sometimes a
      problem in Accuitomo images. In 32 of the 46 cases, all observers agreed that
      additional clinically relevant information was obtained with Accuitomo images.
      CONCLUSIONS: A high-resolution 3D technique can be of value for diagnosis of
      periapical problems.

PMID- 17178505
TI  - Cross-sectional analysis of root canals prepared with NiTi rotary instruments and
      stainless steel reciprocating files.
AB  - OBJECTIVE: To determine whether the shaping of oval-shaped root canals using 2
      different preparation techniques resulted in significant morphologic differences.
      STUDY DESIGN: Forty lower premolars with oval-shaped root canals were divided
      into group A, instrumented with the Anatomic Endodontic Technology (AET) system,
      and group B, treated with ProTaper instruments. A modified Bramante technique was
      used to analyze changes in root canal diameters (DeltaD), changes in surface area
      (DeltaA), and the change in buccolingual and mesiodistal ratio (DeltaR). The data
      were subjected to a Student t test at a significance level of P < 0.05. RESULTS:
      Statistically significant differences were found between the 2 groups at coronal
      and middle levels. There was no statistically significant difference at the
      apical level. CONCLUSIONS: The 2 techniques produced a significant difference in
      the ultimate shape of the coronal and middle portions of oval-shaped root canals,
      with the AET system removing more tooth structure at these levels. However, no
      differences were observed at the apical third.

PMID- 17178506
TI  - Interrelation between endodontic status, pathologic cemental granules and
      periodontal ligament adhering to the root of extracted teeth.
AB  - OBJECTIVES: To evaluate if the endodontic status has influence on the adherence
      of periodontal ligament (PDL) to extracted teeth and if the presence of
      "pathologic granules" is correlated to the endodontic status and/or the amount of
      adhering PDL. STUDY DESIGN: Extracted teeth with different endodontic status and
      exhibiting no marginal periodontitis were histologically examined. RESULTS:
      Observation of pathologic granules was related to a nonvital endodontium and to
      acute peroperative inflammation. Pathologic granules and denudation of the
      extracted roots were significantly related. Acute peroperative inflammation and
      low extraction forces were related to denudation of the roots. Such relation was
      not found for endodontic status, tooth type, root-form, and age of patients.
      CONCLUSION: The existence of pathologic granules in unexposed cementum is
      strictly related to teeth with a nonvital endodontium. There is no effect of the
      endodontic status on the adherence of PDL when an acute inflammation is absent.

PMID- 17178507
TI  - Age- and tooth-related pulp cavity signal intensity changes in healthy teeth: a
      comparative magnetic resonance imaging analysis.
AB  - OBJECTIVE: To determine if it is possible to measure age-related pulp cavity
      signal intensity changes by using magnetic resonance imaging (MRI). STUDY DESIGN:
      Dental pulp cavity signal intensities were assessed in 92 test subjects on the
      basis of MRI signal intensity measurements at freely defined regions of interest
      by using T1 gradient echo sequences before and after contrast-agent
      administration. Relative signal intensity differences were calculated and
      provided the basis for age- and tooth-related comparisons. RESULTS: Significant
      signal intensity differences were noted between the oldest (born between 1930 and
      1959) and the youngest (born after 1980) test subjects and the other groups (P <
      .05). In addition, the first molars showed significantly lower signal intensity
      differences than the second molars (P < .05). CONCLUSION: Magnetic resonance
      imaging can be used to determine pulp cavity signal-intensity changes with age.

PMID- 17178510
TI  - Medical professionalism and social accountability in medical education.

PMID- 17178508
TI  - The effect of three different sealers on the radiopacity of root fillings in
      simulated canals.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of 3 root canal
      sealers on radiopacity of root fillings in simulated canals by means of direct
      digital radiography. STUDY DESIGN: Thirty simulated root canals in transparent
      acrylic blocks were prepared with a 4% tapered, size 25 instrument. A single 4%
      tapered, size 25 gutta-percha cone was inserted into each canal. Standardized
      images of the blocks with an aluminum step-wedge were obtained by using Digora
      storage phosphor plates. Then, 3 root canal sealers (Roeko, Diaket, Pulpdent)
      were mixed according to the manufacturers' instructions. The gutta-percha cones
      were completely coated with one of the sealers and placed in the identical canal
      to the full working length. The images of the blocks were reobtained after sealer
      application. The mean gray values (MGVs) of root fillings were measured with or
      without the sealer at 3 different levels (1 mm, 6 mm, and 11 mm from apex) by
      using the Image Tool program. Each MGV measurement was then converted to its
      aluminum equivalent by means of the step-wedge values. A paired t test was used
      for statistical analysis. RESULTS: RoekoSeal caused a significant decrease in the
      radiopacity of the root fillings at the 1-mm level (P < 0.01). Diaket and Pulp
      Canal Sealer (PCS) increased the radiopacity of the fillings at all levels
      significantly (P < 0.01) except 6- and 11-mm levels of the Diaket specimens (P >
      0.05). CONCLUSION: The type and the thickness of root canal sealers can influence
      the radiopacity of the root fillings.

PMID- 17178511
TI  - Learning strategies used by cardiology residents: assessment of learning styles
      and their correlations.
AB  - OBJECTIVE: To identify the learning styles of a group of cardiology residents (R)
      undergoing a training program at the University of Buenos Aires and to identify
      correlations of these styles. METHODS: Statistical data were obtained through a
      120-question survey developed by Vermunt and colleagues, which identified four
      different learning styles: construction-directed; reproduction-directed;
      application-directed; and undirected. Four variables were identified [gender,
      previous experience as a teaching assistant (TA) in medical school, university
      final average (FA) and the public or private institution/centre of origin] in
      order to analyse level of correlation with learning styles (LS). Between April
      2001 and April 2002, 149 residents (R) completed the survey. Average age was 29
      (+/-2.7) years old; with 63% being men. FINDINGS: The predominant LS were
      oriented toward knowledge application. In terms of variables, no differences
      regarding gender were detected; the R with TA showed undirected LS
      characteristics; those with a low FA registered a tendency towards reproduction
      directed LS; and those residents at public/state medical centres indicated
      construction-directed LS tendencies. CONCLUSION: An application-directed learning
      style predominates in this group of residents. Information regarding learning
      styles can provide foundations upon which arguments can be made for changes in
      education that are traditionally not evidence-based.

PMID- 17178512
TI  - Improving the performance of the health service delivery system? Lessons from the
      Towards Unity for Health projects.
AB  - CONTEXT: The World Health Organization developed the Towards Unity for Health
      (TUFH) strategy in 2000 for the improvement of health system performance. Twelve
      projects worldwide were supported to put this strategy into practice. A standard
      evaluation and monitoring framework was developed on the basis of which project
      coordinators prepared technical progress reports. OBJECTIVES: To review the
      utility and effectiveness of the evaluation criteria recommended by TUFH and
      their application in four of the original twelve projects. METHODS: We reviewed
      status reports provided by European project coordinators and developed a
      standardized reporting template to extract information using original TUFH
      evaluation criteria. RESULTS: The original TUFH evaluation framework is very
      comprehensive and has only partly been followed by the field projects. The
      evaluation strategies employed by the projects were insufficient to demonstrate
      the connections between the intervention and the desired process improvements,
      and few of the evaluation measures address outcomes. DISCUSSION: The evaluation
      strategies employed by the projects are limited in allowing us to associate the
      intervention with the desired process improvements. Few measures address
      outcomes. The evaluation of complex community interventions poses many
      challenges, however, tools are available to assess impact on structures and
      process, and selected outcome indicators may be identified to monitor progress in
      future projects. CONCLUSION: Based on the review of evaluation status of the TUFH
      projects and resources available we recommend moving away from uniform evaluation
      and towards monitoring minimal, context-specific performance indicators criteria.

PMID- 17178513
TI  - Comparison of communication skills in medical residents with and without
      undergraduate communication skills training as provided by the Faculty of
      Medicine of Gadjah Mada University.
AB  - OBJECTIVE: To promote better doctor-patient relationships in clinical practice,
      many medical faculties have introduced practical communication skills training
      programs for their students. This study is aimed at comparing the communication
      skills of graduates of the Faculty of Medicine of Gadjah Mada University,
      Indonesia, educated with and without communication skills training as perceived
      by their patients and by the graduates themselves. METHODS: Over 300 patients
      were seen by 18 medical residents trained in communication skills before
      graduation and 30 residents who had not attended this training. After
      consultation patients and residents completed a 39-item questionnaire addressing
      the doctor's communication behavior skills. In the questionnaires completed by
      patients the desired communication behavior of doctors was also rated. RESULTS:
      Patients did not observe any differences in communication behavior skills among
      residents who received training and those who did not. These two groups of
      trained and non-trained residents assessed their own communication behavior
      skills. On 4/39 questionnaire items patients rated the communication behavior
      skills of trained residents lower than the residents themselves and the ratio was
      13/39 for non-trained residents. A significant gap was noted between doctors'
      communication behavior skills as observed and desired by their patients (p <
      0.001). CONCLUSIONS: Undergraduate communication skills training in the
      institution under study could not be demonstrated to illustrate a difference in
      the communication behavior skills of its graduates from graduates from the same
      institution who did not attend communication skills training. Trained graduates,
      however, were more aware of communication behavior skills as being preferred by
      their patients than their peers who were not trained in communication behavior
      skills training during their undergraduate studies.

PMID- 17178514
TI  - Development and implementation of a nutrition education program for medical
      students: a new challenge.
AB  - CONTEXT: Teaching nutrition to medical students is constrained by limitations in
      curricular time and competition with other topics. OBJECTIVES: To identify time
      slots and teaching methods for incorporating nutrition into the medical school
      curriculum, determine students' nutritional knowledge following the program, and
      their perception of the effectiveness of the program. METHODS: A nutritional
      workshop was added to the clinical experience weeks of second-year medical
      students. The first class included 66 students and the second class included 56
      students. In order to fully acquaint the students with nutrition, four topics
      were included: nutritional policy, dietary assessment, nutritional
      recommendations, and obesity. Students were encouraged to actively participate in
      the program which included dietary intake interviews, debates regarding
      nutritional treatments, and actual practice in class. The main outcome measures
      were nutritional knowledge and evaluation of the program by the students.
      FINDINGS: Over 90% of the students answered the knowledge questions correctly.
      The effectiveness of the training was graded (on a scale of 1-7) between 3.7-5.4
      in the first year and 3.4-5.7 in the second year. CONCLUSIONS: The ten-hour
      nutritional workshops within the clinical weeks were well-received by second-year
      medical students. Using cases relevant to the students' age seems to enhance
      their interest in the program.

PMID- 17178515
TI  - A collaborative approach to developing a validated competence-based curriculum
      for health professions students.
AB  - PROBLEM: Curricula are developed to educate health professions students to
      provide efficient and effective health services. In addition to learning their
      disciplinary perspective, today's students must master the concepts of
      multidisciplinary team care. Traditionally, curriculum was developed based
      primarily on the perspectives of the discipline faculty, administration and
      accrediting agencies. However, now there are multiple groups (other academic
      educators, consumers and employers of health care providers) who may hold
      differing perspectives about outcomes expected from these programs. PURPOSE: The
      purpose of this investigation was to use an innovative methodology to generate
      and validate a curriculum for health professions students from multiple
      disciplines. METHOD: A multi-phased method using focus groups, surveys,
      dissemination and affirmation was presented to identify the concepts and best
      practices that should be included. RESULTS: Several performance-based themes
      evolved during the interviews and a questionnaire was generated. Academic
      educators, consumers and employers of health care providers indicated agreement
      that the components on the survey were realistic and important for health
      professions students to achieve. Thus, outcomes for a curriculum were validated.
      The faculty rated several components of the curriculum as less realistic for
      students to achieve than did the consumers and employers. This investigation
      suggests it may be necessary for faculty to assist providers and parents in
      developing more realistic expectations about what students can achieve during
      their educational program. The approach used in this current project moves the
      field of the health professions curriculum development to a different level when
      compared with the traditional curriculum development approaches and should be
      used by others concerned with multi-professional education to assure the validity
      of the curricula.

PMID- 17178516
TI  - Career preference of final year medical students of Ziauddin Medical University.
AB  - PURPOSE: The study aims to identify the career preferences of the final year
      medical student as well as to determine gender differences in career choices.
      PARTICIPANTS: The participants were 232 final year MMBS students of the first
      five classes of Ziauddin Medical University. METHOD: A questionnaire was designed
      that identified student's choice of specialty, location preferences, and reasons
      influencing career preferences. Percentages and chi-square were used to determine
      differences in career preferences of students. RESULTS: Students chose internal
      medicine, surgery, and pediatrics as their first three career choices. Clinical
      specialties were highly rated as compared to family medicine. Personal interest
      was ranked as the most influencing factor that contributed to choice of
      specialty. Most respondents preferred working in Pakistan as compared to
      overseas, and for practice selected, private setup was more favored compared to
      other settings. Gender differences were found in career preferences. CONCLUSION:
      The impact of the innovative community education programme is not clearly evident
      in the study, indicating that several other factors contribute towards decisions
      regarding career. A critical review by the university is required to strengthen
      the fields that are being overlooked by the students. A follow-up study would be
      beneficial to determine the changing trends in career preferences.

PMID- 17178517
TI  - Description and evaluation of a clerkship in International Health and Medicine.
AB  - BACKGROUND AND OBJECTIVES: In 1998 Ben-Gurion University, in collaboration with
      Columbia University, inaugurated the first medical school with the express
      purpose of training students in International Health and Medicine (IHM). The
      highlight of the program is the two-month clerkship in IHM. The purpose of this
      paper is to describe the IHM clerkship and report the preliminary results of an
      evaluation. METHODS: To evaluate the impact of the clerkship on the students'
      attitudes and knowledge of IHM, the students were asked to complete a previously
      validated self-assessment questionnaire before and after the clerkship. RESULTS:
      Ninety-six students participated in the IHM clerkship in the first 3 years. The
      mean age of the students was 29.4 +/- 4 and 53% were female. Comparison of the
      student's answers before their departure and after their return showed a
      significant difference in 5 of 64 items on the questionnaire. There was also a
      significant increase in the overall scores of the female students but no change
      in the scores of the male students pre- and post-clerkship. DISCUSSION AND
      CONCLUSIONS: Our results show that students who completed the clerkship modestly
      increased their knowledge of some aspects of IHM as measured by the survey.
      Further studies on the long-term impact of IHM experiences are needed in parallel
      with efforts to increase medical students' exposure to IHM.

PMID- 17178518
TI  - Perception of students about the problem-based learning sessions conducted for
      medical and dental schools' students of Universiti Sains Malaysia.

PMID- 17178519
TI  - Problems encountered with a pilot online attendance record and feedback scheme
      for medical students.

PMID- 17178520
TI  - Early barriers for university rural clinical placements.

PMID- 17178522
TI  - The World Health Report 2006: working together for health.

PMID- 17178521
TI  - An interprofessional communication skills lab: a pilot project.

PMID- 17178523
TI  - What can we do for childhood obesity? Let's go dancing!

PMID- 17178524
TI  - An interview of Cosme Ordonez Carceller: interview by Jane Westberg.

PMID- 17178526
TI  - Following the role model: identification or survival strategy?

PMID- 17178531
TI  - Effects of embedded instruction versus discrete-trial training on self-injury,
      correct responding, and mood in a child with autism.
AB  - BACKGROUND: Embedded instruction and discrete-trial training are both recommended
      for teaching children with autism, but there is little research available
      comparing the two. The present study compared embedded instruction with discrete
      trial training for a 12-year-old boy with autism. METHOD: An initial functional
      analysis indicated that the boy's self-injury was maintained by escape from task
      demands. Instructional sessions to teach adaptive behaviours were conducted under
      two conditions: (i) during embedded instruction, learning trials were inserted
      into ongoing activities at a rate of approximately 1.5 per minute; (ii) during
      discrete-trial training, instructional opportunities were incorporated into
      structured sessions at a rate of 4 per minute. In both conditions, the system of
      least prompts was used to teach relevant target responses. Effects of the two
      teaching formats were evaluated using an ABABA design. RESULTS: Higher rates of
      self-injury and fewer correct responses occurred during discrete-trial training.
      Mood ratings were also lower during discrete-trial training. CONCLUSIONS: The
      results suggest that self-injury, correct responding, and mood may be sensitive
      to the type of instructional format. Although discrete-trial training can be
      highly effective, it may be preferable to start with embedded instruction when
      the child presents with self-injurious escape behaviour.

PMID- 17178532
TI  - Dietary status and impact of risperidone on nutritional balance in children with
      autism: a pilot study.
AB  - BACKGROUND: Risperidone may be effective in improving tantrums, aggression, or
      self-injurious behaviour in children with autism, but often leads to weight gain.
      METHOD: Using a quantitative Food Frequency Questionnaire (FFQ), we prospectively
      examined the nutritional intake of 20 children with autism participating in a
      randomised placebo-controlled trial of risperidone for disruptive behaviours.
      RESULTS: At baseline, the mean intakes for macronutrients, vitamins and minerals
      exceeded Dietary Reference Intakes (DRIs). However there was substantial inter
      participant variability, with individual deficiencies (<80% of DRI) in the intake
      of calcium (9 of 20 participants), pantothenic acid (6 of 20), vitamin D (5 of
      20) and vitamin K (8 of 20). For the participants for whom FFQs were available,
      there was an increase in weight and an increase in vitamin K intake after 2
      months of risperidone treatment (n = 9) compared to placebo (n = 8). An
      additional 4 months of risperidone treatment (n = 8) did not result in
      significant changes in reported nutritional balance. CONCLUSION: These pilot data
      suggest that treatment with risperidone did not significantly affect the
      nutritional balance of this small group of children.

PMID- 17178533
TI  - Young people with Down syndrome: a preliminary investigation of health knowledge
      and associated behaviours.
AB  - BACKGROUND: Adults with intellectual disability have a range of significant
      health problems. If they are to live independently, they need to engage in
      behaviours that are health promoting, as well as avoiding behaviours that might
      directly lead to ill health. There is very little research about health-related
      knowledge and behaviour in this group. METHOD: A group of 38 adolescents with
      Down syndrome (DS) and their families participated in this study. A semi
      structured interview and a series of tasks were used to collect data on
      individuals' health knowledge and behaviour relating to 4 aspects of health:
      hygiene, substance use, exercise and healthy eating. RESULTS: While the majority
      of young people demonstrated some awareness of basic hygiene, they were not yet
      at the level where these behaviours could be guaranteed to occur without parental
      support. Knowledge about substance use, exercise and healthy food was generally
      poor. CONCLUSION: Knowledge of most aspects of health assessed in this study was
      poor and pointed to a gap in the preparation of these young people for
      independent living.

PMID- 17178534
TI  - Persistence in high school: experiences of adolescents and young adults with
      Fetal Alcohol Spectrum Disorder.
AB  - BACKGROUND: This study examined persistence in high school among students with
      Fetal Alcohol Spectrum Disorder (FASD) from the perspective of the adolescents
      themselves. Tinto's (1975, 1997) Student Integration Model (SIM) provided the
      theoretical framework for the research. This model consists of three factors:
      background characteristics, academic integration, and social integration. METHOD:
      A collective case study method involving 8 adolescents with FASD from Canada and
      the United States was used. RESULTS: Although the students did not meet the usual
      academic standards and had acquaintances rather than friends, they perceived
      themselves as academically and socially successful. It was shown that persistence
      occurred largely because of the strong support of, and advocacy by, the adoptive
      parents. CONCLUSIONS: Parental advocacy is an environmental factor that may
      protect adolescents with FASD from dropping out of high school.

PMID- 17178535
TI  - Students with mild disabilities in regular classrooms: the development and
      utility of the Student Perceptions of Classroom Support scale.
AB  - BACKGROUND: There is a dearth of empirical research pertaining to the perceptions
      of students with mild disabilities of the academic and social outcomes of
      classroom support mechanisms. The absence of suitable measures is a primary issue
      contributing to this situation. METHOD: The present study reports the development
      and utility of the Student Perceptions of Classroom Support (SPCS) scale, which
      was specifically designed to assess students' perceptions of curricular,
      instructional, physical, and peer support received in regular classrooms from
      both an academic and social perspective. The SPCS was administered to 60
      secondary school-aged students with mild disabilities who experienced both
      regular classroom and traditional special education. RESULTS: Person and item
      discrimination analyses, and calculation of internal consistencies (Cronbach's
      alpha) revealed the SPCS to have excellent psychometric properties (alpha = 0.92
      for academic outcomes and alpha = 0.87 for overall social outcomes). Internal
      consistencies for each of the subscales are also reported. CONCLUSIONS: The SPCS
      provides educators with a valid method of assessing students' preferred support
      strategies, which can then be articulated within Individual Education Plans
      (IEPs).

PMID- 17178536
TI  - Data collections on congenital disabilities: more than just numbers.

PMID- 17178537
TI  - Special education disproportionality and the influence of intelligence test
      selection.

PMID- 17178538
TI  - Why are conferences "Sometimes about us, without us"?

PMID- 17178539
TI  - The Disability Services Act 1986: twenty years on.

PMID- 17178540
TI  - The vision of the Disability Services Act 1986: a never-ending struggle.

PMID- 17178543
TI  - Age-related changes in tactile spatial resolution from 6 to 16 years old.
AB  - The aim of this study was to determine age-related changes in tactile spatial
      resolution from 6 to 16 years old. Two hundred and twenty-two healthy children
      (105 boys and 117 girls) were assessed. The tactile spatial resolution threshold
      was determined using a classic set of JVP domes with a procedure adapted for
      children. Preadolescence appears to be an important step in tactile spatial
      resolution since children aged between 6 and 9 years old had a worse tactile
      spatial resolution than older children. Both peripheral and central explanations
      for this improvement of tactile spatial resolution with age are considered. The
      authors suggest that cortical maturational processes are likely to explain the
      better results of older children.

PMID- 17178544
TI  - Influence of nitric oxide on the activity of cuneate neurons in the rat.
AB  - Some neurons of main and external cuneate nuclei are immunoreactive for nitric
      oxide (NO) synthase, suggesting a role for endogenous NO in the early stages of
      somatosensory processing. We tested this hypothesis by investigating the
      possibility that NO modulates cuneate discharge. We observed that both
      spontaneous and N-methyl-D-aspartate-evoked activities of cuneate neurons were
      decreased by NO precursor L-arginine. The inhibition of NO synthase, by
      application of N-nitro-L-arginine methyl ester, instead, abolished the depressant
      effect induced by L-arginine. Our data suggest a NO modulation of cuneate neurons
      and provide support for a physiologic role not only in increasing the signal-to
      noise ratio in the excited cells but also in a form of surround inhibition.

PMID- 17178545
TI  - Pressure pain sensitivity and hardness along human normal and sensitized muscle.
AB  - The spatial distribution of pressure sensitivity and muscle hardness was examined
      on normal muscle tissue and muscle tissue after induction of delayed onset muscle
      soreness (DOMS). The pressure sensitivity and muscle hardness were assessed at
      nine sites on the tibialis muscle from the proximal to distal tendon on two
      separate days. In total 37 healthy volunteers participated in three experiments.
      In the first experiment pressure pain threshold (PPT) and pressure pain tolerance
      (PPTO) were assessed. Decreased PPT and PPTO were found on day 2, 7 days after
      day 1. Proximal and distal stimulation sites were harder compared to muscle belly
      sites. In a second experiment two different probe sizes were used. Variation in
      PPT between the nine sites was found for the large probe with muscle belly being
      less sensitive to pressure stimulation compared to proximal and distal sites. The
      most proximal stimulation site was harder compared to muscle belly sites. In a
      third experiment PPT and muscle hardness were assessed before and 48 h after
      eccentric exercise. PPT at two muscle belly sites was significantly decreased
      during DOMS. No specific sites were harder during DOMS, the average muscle
      hardness across sites was however significantly increased. Decreased PPT and
      increased muscle hardness did not correlate. In conclusion, within subjects the
      pressure sensitivity varies along the musculoskeletal unit. In DOMS, specific
      muscle belly sites were more sensitive to pressure stimulation. Muscle-tendon
      sites were harder compared to muscle belly sites.

PMID- 17178546
TI  - Adaptation of trigeminal ganglion cells to periodic whisker deflections.
AB  - Trigeminal ganglion neurons in adult rats adapt to periodic whisker deflections
      in the range of 1-40 Hz, manifested as a reduction in spike counts to
      progressively later stimuli in a train of pulsatile or sinusoidal deflections.
      For high velocity, pulsatile deflections, adaptation is time- and frequency
      dependent; as in the case of thalamic and cortical neurons, adaptation is greater
      at higher stimulus frequencies. With slower velocity, sinusoidal movements,
      trigeminal ganglion cells differ from central neurons, however, by exhibiting
      strong adaptation even at low frequencies. For both types of stimuli, effects in
      trigeminal ganglion neurons were more pronounced in rats maintained during the
      recording session under neuromuscular blockade than in non-paralysed animals.
      Results are consistent with previous findings in other systems that frequency
      dependent adaptation of cutaneous primary afferent neurons is affected by
      mechanical properties of the skin. Such effects are likely to vary depending on
      the nature of the whisker stimuli and physiological states that affect skin
      viscoelasticity.

PMID- 17178547
TI  - Ovoid geometry of the Pacinian corpuscle is not the determining factor for
      mechanical excitation.
AB  - Static displacements in Pacinian corpuscles (PCs) were measured using video
      microscopy. Mechanical stimuli of 10-40 microm steps were applied to the PC
      capsule surfaces using cylindrical contacts with different diameters.
      Displacements parallel to the stimulation axis were measured at various locations
      in the focal plane of the optical setup. In contrast to previous data in the
      literature, the displacements within the corpuscle were found to be linearly
      related to the indentation amplitude. Displacements decreased as a function of
      lamella depth, with a more negative slope close to the surface and less negative
      slope at deeper locations. The experimental data were compared to the predictions
      of a previous mechanical model, and to the results of two new models: (1) elastic
      semi-infinite continuum model; (2) ovoid isotropic finite-element model. Although
      the previous model did not specify displacement boundary conditions, it predicted
      the current experimental results well. On the other hand, the experimental
      displacements were found to be smaller than those predicted by the semi-infinite
      continuum and finite-element models. However, both semi-infinite continuum and
      finite-element models yielded close results, which show that the three
      dimensional ovoid geometry of the corpuscle is not the primary factor for
      determining the displacements in physiological conditions. Furthermore,
      simulations with the finite-element model using a wide range of material
      properties yielded similar results. This supports the hypothesis that a
      homogeneous isotropic model for the PC cannot predict experimental results. The
      modeling analyses suggest that the experimental results are largely affected by
      the displacement of the incompressible interlamellar fluid and the layered
      structure of the corpuscle.

PMID- 17178548
TI  - Cyclic modulation of H-reflex depression in ipsilateral and contralateral soleus
      muscles during rhythmic arm swing.
AB  - The objective of the present study was to investigate the effects of rhythmic arm
      swing on ipsilateral and contralateral soleus motoneuron pool excitability. Ten
      healthy human subjects participated in this study. Soleus H-reflexes were
      recorded from the ipsilateral and contralateral soleus muscles while the subject
      swung the right arm anteroposteriorly as if during gait. The soleus H-reflex was
      depressed throughout the whole arm swing cycle except in the ipsilateral leg
      during the onset of the backward arm swing, and in the contralateral leg during
      the last half of the backward arm swing and the onset of the forward arm swing.
      The depression was cyclically modulated in accordance with the time course of the
      arm swing periods, and the pattern of the modulation was reciprocal between the
      ipsilateral and contralateral legs. This cyclical and reciprocal modulation may
      be related to the regulation of soleus motoneuron pool excitability during gait.

PMID- 17178549
TI  - Immediate-early gene expression in the barrel cortex.
AB  - Since their detection in the early 1980s immediate-early genes (most of them
      being inducible transcription factors) have been regarded as molecular keys to
      the orchestration of late-effector genes that ultimately would enable functional
      and structural adaptation of the brain to changing external and internal demands.
      This is called neuronal plasticity and it has been intensively studied in the
      somatosensory (barrel) cortex of rodents. This brain region is intimately
      involved in the processing and probably also the storage of tactile information,
      stemming from the large facial whiskers, necessary for object detection or
      spatial navigation in the environment. On the other hand, several of the
      inducible transcription factors have been found to function as neuronal activity
      markers providing a cellular resolution, thus, enabling the cell-type specific
      mapping of activated neuronal circuits. Some recent data on both topics in the
      rodent barrel cortex will be presented in this topical review.

PMID- 17178550
TI  - Age differences in tactile pattern recognition at the fingertip.
AB  - Young (21-26 years, n=20) and old (55-86 years, n=25) participants were tested
      for their ability to recognize raised letters (6-mm high, 1-mm relief) by touch.
      Spatial resolution thresholds were also measured with grating domes to derive an
      index of the degree of afferent innervation at the fingertip. Letter recognition
      in the young group was very consistent and highly accurate (mean, 86% correct),
      contrasting with the performance of the old group, which was more variable and
      comparatively low in accuracy (mean, 53% correct). In both groups, spatial
      resolution thresholds accounted for a substantial portion of the variance in the
      performance, suggesting a strong link between age-dependent variations in tactile
      innervation and recognition accuracy. The patterns of errors in the old group
      showed that an inability to encode internal elements specific to certain letters
      was at the source of most confusion among letters. Whether this inability
      reflected only deficient peripheral encoding mechanisms or some other alterations
      at the central level is discussed.

PMID- 17178551
TI  - Editorial comment on four papers about testosterone deficiency presented at the
      5th World Congress on the Aging Male.

PMID- 17178552
TI  - Testosterone and body functions.
AB  - Testosterone supplementation can help reduce many of the symptoms associated with
      androgen deficiency in the aging male by its effects on various parts of the
      body. Bone mineral density can decrease in the hypogonadal man and this may
      contribute to the increased fracture rate in the elderly. Testosterone therapy
      can improve bone mineral density and bone architecture by increasing bone
      formation and decreasing bone resorption - the possible benefits on fracture rate
      are unknown. Testosterone also improves body composition by reducing body fat
      mass and increasing lean body mass, and by increasing epidermal thickness, but
      its effects on muscle strength are still debated. In patients with diabetes and
      androgen deficiency, testosterone supplementation appears to reduce blood glucose
      and this could have important implications for cardiovascular risk reduction in
      patients with diabetes or the metabolic syndrome. The wide-ranging benefits of
      testosterone therapy in young and old men are clear and it appears that the route
      of administration (intramuscular, oral, or transdermal) does not alter this fact,
      but future work could illustrate even more profound effects of testosterone
      (e.g., in reducing cardiovascular risk) that could result in its recommended use
      in a wider range of patients.

PMID- 17178553
TI  - Testosterone and men's quality of life.
AB  - As the worldwide population ages, the emphasis on having a reasonable quality of
      life in old-age is increasing. In men, age-associated testosterone decline is one
      of the major factors that reduce quality of life. In patients and the physicians
      treating them, decreased energy levels and impairments to sex-life are perceived
      as the most important effects of hypogonadism. Two quality of life scales, the
      Aging Males' Symptoms (AMS) and the Age-Related Hormone Deficiency-Dependent
      Quality of Life (A-RHDQoL) scales, have recently been developed to specifically
      assess this patient population, and the A-RHDQoL found that memory, energy and
      physical capabilities, and sex-life were the factors most adversely affected by
      low testosterone levels. Unfortunately, there are limited data on the effects of
      testosterone on the quality of life of men with hypogonadism, but the information
      that exists suggests that testosterone can improve the quality of life
      significantly (to the same level as men with normal testosterone levels) and the
      more severe the symptoms before treatment, the greater the benefits of
      testosterone replacement. These promising early results need to be confirmed in
      more detailed quality of life studies.

PMID- 17178554
TI  - Testosterone and the brain.
AB  - Gender differences in spatial recognition, and age-related declines in cognition
      and mood, point towards testosterone as an important modulator of cerebral
      functions. Testosterone appears to activate a distributed cortical network, the
      ventral processing stream, during spatial cognition tasks, and addition of
      testosterone improves spatial cognition in younger and older hypogonadal men. In
      addition, reduced testosterone is associated with depressive disorders. The
      relationship between depression and testosterone appears to partly depend upon
      the androgen receptor genotype of the patient, and in appropriate patients with
      low testosterone levels, testosterone substitution can increase positive mood and
      decrease negative mood. The much publicized link between testosterone and
      aggression is probably only of importance in athletes who supplement their
      testosterone levels to excessively high levels, whereas in hypogonadal men,
      testosterone supplementation only enhances the positive aspects of aggression
      such as vigour and energy. Current data suggest that testosterone supplementation
      in hypogonadal men of all ages will enhance many aspects of mood and cognition.

PMID- 17178555
TI  - Testosterone and erectile physiology.
AB  - The role of testosterone deficiency in sexual dysfunction is an important aspect
      of aging, because it affects such a large proportion of men over 50 years old. A
      number of age-related factors can cause sexual dysfunction (in particular
      erectile dysfunction) and testosterone deficiency, such as chronic illness and
      multiple medications, and the causative link between hypogonadism and erectile
      dysfunction is still debated. However, studies in castrated animals have proven
      that addition of testosterone, and its conversion to dihydrotestosterone, can
      restore erectile function. It appears that testosterone achieves this by
      peripheral mechanisms (endothelial dependent and independent) and central
      mechanisms. Testosterone replacement therapy is therefore effective for erectile
      dysfunction in men with hypogonadism, with success rates of 35-40%. Testosterone
      supplementation is also important in men who fail on phosphodiesterase type-5
      inhibitors, because a minimum plasma concentration of testosterone is required
      for the successful restoration of erectile function with these agents.
      Testosterone gels are now the preferred formulation for testosterone
      supplementation and they can be highly beneficial in a proportion of men with
      erectile dysfunction.

PMID- 17178556
TI  - Age related variation of salivary testosterone values in healthy Japanese males.
AB  - OBJECTIVE: We examined age associated variation in salivary testosterone values
      among Japanese males as well as anthropometric measurements. METHODS: Salivary
      samples were collected in pretreated sodium azide treated tubes. The first
      series: 15-79-year-old males (n = 99); two morning and two evening samples were
      collected at home for two days. The second series: 90-year-old males (n = 29);
      one morning sample was collected. Testosterone values were determined using an
      iodine125-based radioimmunoassay kit modified for saliva. RESULTS: Results show
      1) a significant decrease in salivary testosterone values from 20s to 40s and
      older, 2) no significant decline after 40 through 90 years old, 3) no significant
      age-related differences in the degree of intraindividual diurnal fluctuation
      across age groups of 40-70s, and 4) higher BMI is associated with the lower
      salivary testosterone among 40-70s. CONCLUSIONS: These results suggest that
      neither a constant decrease of salivary testosterone values or markedly reduced
      intraindividual fluctations are universal aspects of aging. Older males may
      maintain relatively high testosterone levels compared to younger men and a
      relatively 'robust' neuroendocrinological system.

PMID- 17178557
TI  - Andropause: knowledge and awareness among primary care physicians in Victoria,
      BC, Canada.
AB  - The causes, symptoms and treatment options for andropause have been well
      documented; however, not enough is known about the primary care physicians'
      (PCPs) knowledge in this therapeutic area. This study assesses the PCPs'
      awareness and knowledge of andropause in Victoria, British Columbia, Canada.
      METHODS: Self-administered questionnaires were developed for family physicians
      and general practitioners. Each questionnaire included questions in three
      domains: 1) General knowledge, beliefs and exposure; 2) Knowledge of diagnostic
      and treatment options and; 3) General demographics. RESULTS: A very high
      percentage of PCPs had heard of andropause (96.3%). Of the physicians who
      completed the survey, 92.6% agreed that men experience something similar to
      women's menopause when they age and 98.0% agreed that andropause is associated
      with an increased risk of osteoporosis. Almost all PCPs (91.5%) agreed that
      prostate cancer is a contraindication to treatment while around one-third (33.9%)
      agreed that breast cancer was a contraindication. Slightly more than half of
      physicians (57.4%) felt that they encountered obstacles to their investigation of
      andropause with the most prevalent complaint being a lack of access to education
      resources. There is a need for improved continuing medical education (CME)
      programmes in the Greater Victoria region to give PCPs the skills to diagnose and
      manage andropause with confidence.

PMID- 17178558
TI  - Clinical experience with the new long-acting injectable testosterone undecanoate.
      Report on the educational symposium on the occasion of the 5th World Congress on
      the Aging Male, 9-12 February 2006, Salzburg, Austria.
AB  - This symposium report summarizes first extensive clinical findings with
      injectable testosterone undecanoate (Nebido) in hypogonadal patients showing
      clinical symptoms of androgen deficiency with or without erectile dysfunction
      (ED). This new testosterone formulation (1000 mg testosterone undecanoate in 4 ml
      castor oil) possesses nearly ideal long-term kinetics, i.e. sustained close
      mimicking of eugonadal testosterone serum levels without supra- or sub
      physiological serum concentrations. The generally accepted administration scheme
      recommends the second injection 6 weeks after the first one followed by further
      injections every 12 weeks. Applying this regimen, administration intervals are
      drastically reduced in comparison to conventional i.m. testosterone preparations
      (e.g. about 16 injections of testosterone enanthate vs. 4-5 injections of
      testosterone undecanoate per year). Depending on the testosterone serum levels,
      individualized therapy is possible by shortening (every 10 weeks) or prolonging
      (every 14 weeks) the injection intervals. In hypogonadal patients with ED 58%
      respond to testosterone undecanoate alone. Best results are seen in diabetic
      hypogonadal patients. The regimen of injectable testosterone undecanoate
      administration ideally fits recommendations regarding pharmacokinetics, efficacy
      and safety monitoring.

PMID- 17178560
TI  - Bioinformatics for study of autoimmunity.
AB  - Recent years have witnessed an explosive growth in available biological data
      pertaining to autoimmunity research. This includes a tremendous quantity of
      sequence data (biological structures, genetic and physical maps, pathways, etc.)
      generated by genome and proteome projects plus extensive clinical and
      epidemiological data. Autoimmunity research stands to greatly benefit from this
      data so long as appropriate strategies are available to enable full access to and
      utilization of this data. The quantity and complexity of this biological data
      necessitates use of advanced bioinformatics strategies for its efficient
      retrieval, analysis and interpretation. Major progress has been made in
      development of specialized tools for storage, analysis and modeling of
      immunological data, and this has led to development of a whole new field know as
      immunoinformatics. With advances in novel high-throughput immunology technologies
      immunoinformatics is transforming understanding of how the immune system
      functions. This paper reviews advances in the field of immunoinformatics
      pertinent to autoimmunity research including databases, tools in genomics and
      proteomics, tools for study of B- and T-cell epitopes, integrative approaches,
      and web servers.

PMID- 17178562
TI  - Systems-based medicine approaches to understand and treat complex diseases. The
      example of multiple sclerosis.
AB  - Systems medicine is an emerging concept that acknowledges the complexity of a
      multitude of non-linear interactions among molecular and physiological variables.
      Under this new paradigm, rather than a collection of symptoms, diseases are seen
      as the product of deviations from a robust steady state compatible with life.
      This concept requires the incorporation of mathematics and physics to the more
      classical arsenal of physiology and molecular biology with which physicians are
      trained today. This review explores the diverse types of information that can be
      accumulated towards the understanding of multiple sclerosis (MS), a complex
      autoimmune disease that targets the central nervous system (CNS). The challenge
      of data integration and modeling of dynamical systems is discussed in the context
      of disease susceptibility and response to treatment. A theoretical framework that
      supports the use of combination therapy is also presented.

PMID- 17178561
TI  - PREDNOD, a prediction server for peptide binding to the H-2g7 haplotype of the
      non-obese diabetic mouse.
AB  - The non-obese diabetic (NOD) mouse is a widely used animal model for study of
      autoimmune diseases, in particular human type 1 diabetes mellitus (T1DM).
      Identification of the subset of peptides that bind MHC molecules comprising the H
      2g7 haplotype of NOD mouse and thereby representing potential NOD T-cell epitopes
      is important for research into the pathogenesis and immunotherapy of T1DM. The H
      2g7 haplotype comprises the MHC class-I molecules Kd and Db and a single class-II
      molecule I-Ag7. We have developed a prediction system, PREDNOD, for accurate
      identification of peptides that bind the MHC molecules constituting the H-2g7
      haplotype. PREDNOD is accessible at http://antigen.i2r.a-star.edu.sg/Ag7.

PMID- 17178563
TI  - Antigen-induced differential gene expression in lymphocytes and gene expression
      profile in synovium prior to the onset of arthritis.
AB  - To explore early signature genes playing critical roles in the initial steps in
      an autoimmune murine model of rheumatoid arthritis (RA) (proteoglycan (PG)
      induced arthritis; PGIA), we performed gene expression profiling of
      "arthritogenic" spleen cells stimulated with cartilage PG, and compared them to
      differentially expressed genes, identified in joints prior to the onset of
      arthritis, and then in the acute and chronic phases of the disease. A total of
      280 genes were up-regulated and 226 genes were suppressed in in vitro PG
      stimulated lymphocytes at a minimum of 2-fold expression change. Functional gene
      classification identified several major clusters of biological activity.
      Expression of immunoglobulin genes (66 transcripts) was downregulated by
      approximately 3.7-fold, whereas most of the other genes with immune/inflammation
      associated functions such as interleukins (IL-1, -2, -4, -6, -10, -12, -16, -17),
      chemokine receptors and their ligands (Cxcl1, Ccl2, 7, 8, 9, 10, 22, Ccr2, Ccr5),
      and major components of the complement cascade were upregulated. Using adoptive
      disease transfer with stimulated lymphocytes into SCID mice, followed by gene
      expression profiling of SCID paws, indicated that 37 genes were differentially
      expressed in yet non-inflamed (pre-arthritic) paws; these genes were related
      mostly to chemokine, IFN-gamma and TNF-alpha signaling. However, the majority of
      differentially expressed immune response-related genes were silent in pre
      arthritic joints, and only 12 genes were found differentially expressed both in
      antigen (PG)-stimulated lymphocytes and in the synovium prior to the onset of
      arthritis. Most of these "arthritis-initiation" genes belonged to chemokine
      mediated cell motility. Transcripts of chemokine receptor 5 (Ccr5), chemokine
      ligand 7 (Ccl7) and IFN-gamma-inducible proteins (Ifi47) and GTP-ase 1 were
      expressed at the highest levels in both antigen-stimulated lymphocytes and pre
      inflamed synovium, which suggests a key role of these genes in both lymphocyte
      maturation and arthritis initiation.

PMID- 17178565
TI  - Microparticles as mediators of cellular cross-talk in inflammatory disease.
AB  - Microparticles are a heterogeneous population of membrane-coated vesicles which
      can be released from virtually all cell types during activation or apoptosis.
      Release occurs from the cell surface in an exogenous budding process involving
      local rearrangement of the cytoskeleton. Given their origin, these particles can
      be identified by staining for cell surface markers and annexin V. As shown in in
      vitro studies, microparticles may represent a novel subcellular element for
      intercellular communication in inflammation. Thus, microparticles can transfer
      chemokine receptors and arachidonic acid between cells, activate complement,
      promote leukocyte rolling and stimulate the release of pro-inflammatory
      mediators. Under certain conditions, however, microparticles may also exert anti
      inflammatory properties by inducing immune cell apoptosis and the production of
      anti-inflammatory mediators. Microparticles may play an important role in the
      pathogenesis of rheumatologic diseases as evidenced by their elevation in
      diseases such as systemic sclerosis (SSc), systemic vasculitis and
      antiphospholipid antibody syndrome and correlation with clinical events. A role
      in inflammatory arthritis is suggested by the finding that leukocyte-derived
      microparticles induce the production of matrix metalloproteinases and cytokines
      by synovial fibroblasts. Together, these findings point to novel signaling
      pathways of cellular cross-talk that may operate along the spectrum of soluble
      cytokines and mediators of direct cell-cell contact.

PMID- 17178564
TI  - Tolerizing DNA vaccines for autoimmune arthritis.
AB  - Current therapies for rheumatoid arthritis (RA) and other autoimmune diseases non
      specifically suppress immune function, and there is great need for fundamental
      approaches such as antigen-specific tolerizing therapy. In this paper we describe
      development of antigen-specific tolerizing DNA vaccines to treat collagen-induced
      arthritis (CIA) in mice, and use of protein microarrays to monitor response to
      therapy and to identify potential additional autoimmune targets for next
      generation vaccines. We demonstrate that tolerizing DNA vaccines encoding type II
      collagen (CII) reduced the incidence and severity of CIA. Atorvastatin, a statin
      drug found to reduce the severity of autoimmunity, potentiated the effect of DNA
      vaccines encoding CII. Analysis of cytokines produced by collagen-reactive T
      cells derived from mice receiving tolerizing DNA encoding CII, as compared to
      control vaccines, revealed reduced production of the pro-inflammatory cytokines
      IFN-gamma and TNF-alpha. Arthritis microarray analysis demonstrated reduced
      spreading of autoantibody responses in mice treated with DNA encoding CII. The
      development of tolerizing DNA vaccines, and the use of antibody profiling to
      guide design of and to monitor therapeutic responses to such vaccines, represents
      a promising approach for the treatment of RA and other autoimmune diseases.

PMID- 17178566
TI  - Carbohydrate recognition systems in autoimmunity.
AB  - The immune system is a complex functional network of diverse cells and soluble
      molecules orchestrating innate and adaptive immunity. Biological information, to
      run these intricate interactions, is not only stored in protein sequences but
      also in the structure of the glycan part of the glycoconjugates. The spatially
      accessible carbohydrate structures that contribute to the cell's glycome are
      decoded by versatile recognition systems in order to maintain the immune
      homeostasis of an organism. Microbial carbohydrate structures are recognized by
      pathogen associated molecular pattern (PAMP) receptors of innate immunity
      including C-type lectins such as MBL, the tandem-repeat-type macrophage mannose
      receptor, DC-SIGN or dectin-1 of dendritic cells, certain TLRS or the TCR of NKT
      cells. Natural autoantibodies, a long known effector branch of this network-based
      operation, are effective to home in on non-self and self-glycosylation also. The
      recirculating pool of mammalian immune cells is recruited to inflammatory sites
      by a reaction pathway involving the self-carbohydrate-binding selectins as
      initial recognition step. Galectins, further key sensors reading the high-density
      sugar code, exert regulatory functions on activated T cells, among other
      activities. Autoimmune diseases are being associated with defined changes of
      glycosylation. This correlation deserves to be thoroughly studied on the levels
      of structural mimicry and dysregulation as well as effector molecules to devise
      innovative anti-inflammatory strategies. This review briefly summarizes data on
      sensor systems for carbohydrate epitopes and implications for autoimmunity.

PMID- 17178567
TI  - Systems biology in systemic lupus erythematosus: integrating genes, biology and
      immune function.
AB  - Overactive B cells, abnormally activated T cells and inappropriate handling of
      cellular debris by the innate immune system are central in the pathogenesis of
      systemic lupus erythematosus (SLE). Genetic studies in SLE patients have
      unraveled allelic variations in genes encoding key molecules that control inter-
      and intra-cellular signaling and play a role in the abnormal handling of
      apoptotic material. Despite recent breakthroughs though, it is still unclear how
      exactly genes and environment interact to produce the characteristic immune
      dysregulation in SLE.

PMID- 17178568
TI  - Immunomodulation of experimental pulmonary fibrosis by intravenous immunoglobulin
      (IVIG).
AB  - OBJECTIVES: To assess the immunomodulatory effect of intravenous immunoglobulin
      (IVIG) using an experimental model of bleomycin-induced pulmonary fibrosis.
      METHODS: Pulmonary fibrosis was induced in C57BL/6 mice by direct intratracheal
      injection of bleomycin. Mice were treated with IVIG 1 week prior to (prevention
      protocol), or 10 days following bleomycin injection, when the disease was in
      progress. The controls used in the study included mice given phosphate buffered
      saline (PBS) and mice subjected to a commercial individual-IgG. Collagen-I
      deposits in the affected lungs were detected by Sirius red staining of paraffin
      embedded lung sections. The collagen-I content was measured by employing the
      hydroxyproline assay. RESULTS: Prevention of bleomycin-induced pulmonary fibrosis
      by IVIG has been demonstrated by reduced expression of collagen-I protein in the
      affected lungs. The hydroxyproline levels in the lungs of the IVIG-treated mice
      were 214.33 +/- 13.56 microg/1 g tissue, compared to the higher levels in lungs
      of IgG treated mice (342.44 +/- 35.60 microg/1 g tissue) or untreated controls
      328.00 +/- 45.55 microg/1 g tissue, (p < 0.0001). Effective treatment of
      bleomycin-induced pulmonary fibrosis by IVIG has been demonstrated by the reduced
      expression of collagen-I protein in the affected lungs, detected by sirius red
      histological staining. The hydroxyproline levels in the lungs of the IVIG-treated
      mice were 261.00 +/- 18.81 microg/1 g tissue, in comparison to the higher levels
      in the lungs of the IgG treated mice (342.43 +/- 32.89 microg/1 g tissue) and of
      untreated controls (344.33 +/- 49.85 microg/1 g tissue), (p < 0.001).
      CONCLUSIONS: Based on these preliminary studies, we conclude that IVIG may have a
      beneficial effect in the down regulation of collagen-I levels in the lungs of
      mice with bleomycin-induced pulmonary fibrosis.

PMID- 17178569
TI  - Capsular polysaccharides secreted by building facade colonisers: characterisation
      and adsorption to surfaces.
AB  - Exopolymers secreted by algal and cyanobacterial strains isolated from building
      facades were imaged by microscopy techniques. They were extracted and
      characterised to investigate their possible contribution to interactions with
      solid surfaces. The polymers were polysaccharides, with anionic and hydrophobic
      properties varying between the various strains. Capsular polysaccharides
      extracted from a strain of Klebsormidium flaccidum adsorbed in higher amounts on
      hydrophobic than on hydrophilic surfaces. These results tend to confirm the
      hypothesis that exopolymers are important in the colonisation process of
      microorganisms to surfaces.

PMID- 17178570
TI  - Biofilm formation by Pseudoalteromonas ruthenica and its removal by chlorine.
AB  - The distribution of a recently described marine bacterium, SBT 033 GenBank
      Accession No. AY723742), Pseudoalteromonas ruthenica, at the seawater intake
      point, outfall and mixing point of an atomic power plant is described, and its
      ability to form biofilm was investigated. The effectiveness of the antifouling
      biocide chlorine in the inactivation of planktonic as well as biofilm cells of P.
      ruthenica was studied in the laboratory. The results show that the planktonic
      cells were more readily inactivated than the cells enclosed in a biofilm matrix.
      Viable counting showed that P. ruthenica cells in biofilms were up to 10 times
      more resistant to chlorine than those in liquid suspension. Using confocal laser
      scanning microscopy it was shown that significant detachment of P. ruthenica
      biofilm developed on a glass substratum could be accomplished by treatment with a
      dose of 1 mg l-1 chlorine. Chlorine-induced detachment led to a significant
      reduction in biofilm thickness (up to 69%) and substratum coverage (up to 61%),
      after 5-min contact time. The results show that P. ruthenica has a remarkable
      ability to form biofilms but chlorine, a common biocide, can be used to
      effectively kill and detach these biofilms.

PMID- 17178571
TI  - Effects of localised, low-voltage pulsed electric fields on the development and
      inhibition of Pseudomonas aeruginosa biofilms.
AB  - This work describes the use of low-voltage (0.5 - 5 V) pulsed electric fields to
      prevent Pseudomonas aeruginosa biofilm development. Interdigitated electrodes
      (IDEs) with 29-mum spacing between 22-mum-wide electrodes, were used as a
      platform where the effect of localised, high-strength electric fields could be
      tested. Alternating current, square-wave pulses were applied to the IDEs in 1 sec
      intervals. A two-level, three-variable factorial design experiment was used to
      detect the effects of applied voltage, frequency, and pulse duty ratio (i.e.
      percentage of pulsing time over one cycle) on the inhibition of biofilm
      formation. The observations indicated that a pulse configuration of 1% duty
      ratio, 5 V, and 200 Hz frequency reduced the area of the electrodes covered by
      biofilm by 50%. In general, the application of low-duty ratio pulses had a
      positive effect on preventing biofouling. Comparatively, frequency and applied
      voltage were observed to have less influence on biofouling.

PMID- 17178572
TI  - Algal antifouling and fouling-release properties of metal surfaces coated with a
      polymer inspired by marine mussels.
AB  - The marine antifouling and fouling-release performance of titanium surfaces
      coated with a bio-inspired polymer was investigated. The polymer consisted of
      methoxy-terminated poly(ethylene glycol) (mPEG) conjugated to the adhesive amino
      acid l-3,4-dihydroxyphenylalanine (DOPA) and was chosen based on its successful
      resistance to protein and mammalian cell fouling. Biofouling assays for the
      settlement and release of the diatom Navicula perminuta and settlement, growth
      and release of zoospores and sporelings (young plants) of the green alga Ulva
      linza were carried out. Results were compared to glass, a poly(dimethylsiloxane)
      elastomer (Silastic T2) and uncoated Ti. The mPEG-DOPA3 modified Ti surfaces
      exhibited a substantial decrease in attachment of both cells of N. perminuta and
      zoospores of U. linza as well as the highest detachment of attached cells under
      flow compared to control surfaces. The superior performance of this polymer over
      a standard silicone fouling-release coating in diatom assays and approximately
      equivalent performance in zoospore assays suggests that this bio-inspired polymer
      may be effective in marine antifouling and fouling-release applications.

PMID- 17178573
TI  - A review of surface roughness in antifouling coatings illustrating the importance
      of cutoff length.
AB  - Surface roughness (SR) can affect the hydrodynamic performance of antifouling
      (AF) coatings and influence the settlement behaviour of fouling larvae, which
      makes it an important parameter in the evaluation of novel coatings. This paper
      reviews the causes and consequences of SR in the shipping industry, the
      methodology used for measuring it, and the importance of measuring and reporting
      it correctly. SR is a parameter that originates from marine engineering, but has
      been used extensively by marine scientists to characterise novel coatings and to
      investigate microtopographies that might inhibit settlement behaviour. One of the
      integral components of the SR measurement is the use of a cutoff filter. This is
      a short-pass filter that lets the high wave-number components through and thus
      separates the waviness from the roughness. Depending on the length of this
      filter, roughness at different levels of magnification can be investigated. Much
      of the published work on SR of AF coatings makes no mention of cutoff length, so
      that the results cannot be compared. It is suggested that an international
      standard is needed and that if more researchers were aware of the significance of
      stating cutoff length when reporting SR, more interdisciplinary work between
      biologists, engineers and material scientists would be possible in this field.

PMID- 17178574
TI  - Contact angle anomalies indicate that surface-active eluates from silicone
      coatings inhibit the adhesive mechanisms of fouling organisms.
AB  - Silicone coatings with critical surface tensions (CST) between 20 and 30 mN m-1
      more easily release diverse types of biofouling than do materials of higher and
      lower CST. Oils added to these coatings selectively further diminish the
      attachment strengths of different marine fouling organisms, without significantly
      modifying the initial CST. In a search for the mechanisms of this improved
      biofouling resistance, the interfacial instabilities of four silicone coatings
      were characterised by comprehensive contact angle analyses, using up to 12
      different diagnostic fluids selected to mimic the side chain chemistries of the
      common amino acids of bioadhesive proteins. The surfaces of painted steel test
      panels were characterised both before and after exposure to freshwater, brackish
      water, and seawater over periods ranging from 9 months to nearly 4 years. Contact
      angle measurements demonstrated significant surface activity of the oil-amended
      coatings both before and after long-term underwater exposure. The surface
      activity of the control (coating without oil) increased as a result of underwater
      exposure, consistent with mild surface chain scission and hydrolysis imparting a
      self-surfactancy to the coating and providing a weak boundary layer promoting
      continuing easy release of attaching foulants. Coatings with additives that most
      effectively reduced biofouling showed both initial and persistent contact angle
      anomalies for the test liquid, thiodiglycol, suggesting lower-shear biofouling
      release mechanisms based upon diminished bioadhesive crosslinking by interfering
      with hydrogen- and sulfhydryl bonds. Swelling of the silicone elastomeric
      coatings by hydrocarbon fluids was observed for all four coatings, before and
      after immersion.

PMID- 17178575
TI  - Short-term testing of antifouling surfaces: the importance of colour.
AB  - Data from short-term biofouling assays are frequently used to evaluate the
      performance of antifouling (AF) coatings. There are a large number of factors,
      however, that may influence community development. One such factor is colour. The
      hypothesis was that differences in colour may impact the short-term development
      of a biofouling community and therefore bias the results. An experiment was
      designed to investigate the effect of black and white substrata on settlement of
      fouling organisms in the field. Both Ulva sp. and Spirorbis sp. had significantly
      higher settlement on black surfaces. This result emphasises the importance of
      considering colour and other factors when undertaking short-term testing of AF
      coatings.

PMID- 17178576
TI  - The effect of solid surface tension and exposure to elevated hydrodynamic shear
      on Pseudomonas fluorescens biofilms grown on modified titanium surfaces.
AB  - The solid surface tension of titanium was varied by using organosilane monolayers
      of various terminations, minimising differences in other material properties.
      Both the quantity of Pseudomonas fluorescens biofilms grown on the modified
      surfaces, and the percentage of biofilm remaining after exposure to hydrodynamic
      shear stress, varied significantly as a function of solid surface tension. The
      quantity of biofilm was less on chloropropyl-terminated surfaces than on an alkyl
      terminated surfaces. However, the percentage of biofilm remaining after exposure
      to hydrodynamic shear stress (which depends on the adhesion and cohesion
      strengths of the biofilm) was less for the alkyl-terminated surface than for the
      chloropropyl-terminated surface, for one of the two sample sets analysed. These
      results demonstrate the importance of differentiating between the quantity of
      biofilm on a surface and the adhesion and cohesion strength of the biofilm, and
      may help explain discrepancies in the existing literature regarding the effect of
      solid surface tension on the propensity of a surface for microfouling.

PMID- 17178578
TI  - Benevento resolution 2006.

PMID- 17178579
TI  - Catania resolution 2002.

PMID- 17178580
TI  - The Precautionary Principle must be guided by EMF research.
AB  - Regulatory action based on the Precautionary Principle is generally guided by the
      results of epidemiology studies. Even though laboratory research on
      electromagnetic fields (EMF) has supplied much relevant information and continues
      to do so, it is often overlooked. Laboratory research has shown that EMF of many
      frequencies stimulate many biological systems, and at low thresholds of both
      field strength and duration. It has also shown that EMF stimulate protein
      synthesis in cells and accelerate electron transfer reactions. In the last few
      years, important practical insights have been provided by the research on the
      cellular stress response, where the same specific biological response is induced
      in cells by both ELF (power frequency) and RF (radio frequency) fields, despite
      the very different energy levels. Since this protective biological response is
      not determined by the level of energy absorbed, safety standards based on the
      best available biological evidence must (1) recognize non thermal protective
      responses and (2) include cumulative exposures across the EM spectrum.

PMID- 17178581
TI  - Setting standards in the presence of developing scientific understanding.
AB  - The setting of standards for potential hazards as result of the application of a
      new technology depends on both the philosophy with respect to risk and the state
      of knowledge about the circumstances under which the technology can cause damage.
      Typically, biological damage is first observed for high levels of exposure and
      short times. As our understanding of the technology and its effects on the
      biology improve, biological effects are observed at lower levels and longer
      exposure times. For extended low-level exposures it also becomes more difficult
      to demonstrate a hazard that is independent of other influences. This has been
      true for electric and magnetic fields both at low and radio frequencies. In this
      article it is recognized that a set number is needed for both manufactures and
      system operators to meet if the technology is to serve the public. It is also
      recommended that the public be presented with tables of relative risks that
      include levels of exposure and other risks for comparison. Three tables of
      relative risks are included as a possible starting point.

PMID- 17178582
TI  - Can EMF exposure during development leave an imprint later in life?
AB  - People in industrialized nations live in an environment of ubiquitous
      electromagnetic field (EMF) exposure, both natural and anthropogenic. The
      intensity, variety, and geographic distribution of anthropogenic EMF exposures
      have grown dramatically since the mid 20th century, with many uses serving, and
      in close proximity to, human populations, such as electric power distribution,
      radio and television transmission, and more recently, personal cell phone
      communication units and transmitting towers. Thus, it is reasonable to ask if
      this EMF exposure could cause alterations in the physiology of developing
      organisms, since they are generally assumed to be the most sensitive to chemical
      stressors. In this report, we review work published beginning in the late 1980s.
      Initial reports indicated that exposure of chicken eggs during embryonic
      development to power-line electric fields of 50 and 60 Hz, at 10 V/m in air
      (which is frequently in locations inhabited by humans), could cause the brain
      tissues of the hatched chickens to respond differently in a particular test. More
      recently, an anecdotal report of human sensitivity to EMF has appeared that shows
      a health-related influence of prior exposure history to particular power-line
      frequencies in chemically sensitized individuals. These reports open the question
      of whether the ambient electromagnetic environment can leave an imprint on
      developing organisms and if such imprint changes have the potential for health
      consequences.

PMID- 17178583
TI  - Some problems in modern bioelectromagnetics.
AB  - One of the main problems of bioelectromagnetics - the unbelievable narrow
      resonance peaks at the cyclotron frequency of the alternating magnetic field -
      was considered. Modern electrodynamics of condensed matter clearly brings out
      that the reason of this phenomenon is extremely low viscosity within coherence
      domains of aqueous electrolytic solutions. The electrochemical model of action of
      combined static and alternating magnetic fields on aqueous solutions of amino
      acids is proposed. The possibility of arising a succession of changes in ionic
      forms in these processes was revealed. The dipole ions (zwitterions) together
      with water molecules electrostatically forming joint groups in the solution,
      create favorable conditions for arising mixed coherence domains there.
      Simultaneously with evolution of the coherent processes in these domains, the
      amino acid zwitterions are transforming into the usual ionic form, fit for
      cyclotron resonance. The development of cyclotron resonance under action of
      combined magnetic fields increases the ion kinetic energy, and the ions leave the
      domains for the incoherent component of the solution according to Del Giudice
      pattern (Comisso et al., 2006; Del Giudice et al., 2002), creating the peak
      current through the solution. Then the ions are transforming little by little
      into zwitterionic form again; after that, the solution becomes ready to react on
      exposure of magnetic fields again. The possibilities for formation of coherence
      domains composed of water molecules together with peptide molecules or protein
      ones are discussed.

PMID- 17178584
TI  - Electrohypersensitivity: state-of-the-art of a functional impairment.
AB  - Recently, a new category of persons, claiming to suffer from exposure to
      electromagnetic fields, has been described in the literature. In Sweden,
      electrohypersensitivity (EHS) is an officially fully recognized functional
      impairment (i.e., it is not regarded as a disease). Survey studies show that
      somewhere between 230,000-290,000 Swedish men and women report a variety of
      symptoms when being in contact with electromagnetic field (EMF) sources. The aim
      of our studies has been to investigate possible alterations, in the cellular and
      neuronal systems of these person' skin. As controls, age- and sex-matched
      persons, without any subjective or clinical symptoms or dermatological history,
      served. Immunohistochemistry using antisera to the previously characterized
      marker substances of interest has been utilized. In summary, it is evident from
      our preliminary data that various alterations are present in the
      electrohypersensitive person' skin. In view of recent epidemiological studies,
      pointing to a correlation between long-term exposure from power-frequent magnetic
      fields or microwaves and cancer, our data ought to be taken seriously and further
      analyzed.

PMID- 17178585
TI  - Electromagnetic hypersensitivity: biological effects of dirty electricity with
      emphasis on diabetes and multiple sclerosis.
AB  - Dirty electricity is a ubiquitous pollutant. It flows along wires and radiates
      from them and involves both extremely low frequency electromagnetic fields and
      radio frequency radiation. Until recently, dirty electricity has been largely
      ignored by the scientific community. Recent inventions of metering and filter
      equipment provide scientists with the tools to measure and reduce dirty
      electricity on electrical wires. Several case studies and anecdotal reports are
      presented. Graham/Stetzer (GS) filters have been installed in schools with sick
      building syndrome and both staff and students reported improved health and more
      energy. The number of students needing inhalers for asthma was reduced in one
      school and student behavior associated with ADD/ADHD improved in another school.
      Blood sugar levels for some diabetics respond to the amount of dirty electricity
      in their environment. Type 1 diabetics require less insulin and Type 2 diabetics
      have lower blood sugar levels in an electromagnetically clean environment.
      Individuals diagnosed with multiple sclerosis have better balance and fewer
      tremors. Those requiring a cane walked unassisted within a few days to weeks
      after GS filters were installed in their home. Several disorders, including
      asthma, ADD/ADHD, diabetes, multiple sclerosis, chronic fatigue, fibromyalgia,
      are increasing at an alarming rate, as is electromagnetic pollution in the form
      of dirty electricity, ground current, and radio frequency radiation from wireless
      devices. The connection between electromagnetic pollution and these disorders
      needs to be investigated and the percentage of people sensitive to this form of
      energy needs to be determined.

PMID- 17178586
TI  - Extremely low frequency 7 Hz 100 microT electromagnetic radiation promotes
      differentiation in the human epithelial cell line HaCaT.
AB  - Electromagnetic therapy is a treatment method in which an electromagnetic or
      magnetic stimulus is used to achieve physiological changes in the body. The
      specific aim of the present work concerns the effectiveness of low frequency
      electromagnetic fields to modify the biochemical properties of human
      keratinocytes (HaCaT). Cells exposed to a 7 Hz 100 microT electromagnetic field
      for one hour (twice daily), indicated modification in shape and morphology. These
      modifications were also associated with different actin distribution as revealed
      by phalloidin fluorescence analysis. Indirect immunofluorescence with fluorescent
      antibodies against involucrin and beta-Catenin, both differentiation and adhesion
      markers, revealed an increase in involucrin and beta-Catenin expression,
      supporting the conclusion that exposure to electromagnetic field carries
      keratinocytes to an upper differentiation level. This study confirms our previous
      observation and supports the hypothesis that 7 Hz electromagnetic field, may
      modify cell biochemistry interfering in the differentiation and cellular adhesion
      of normal keratinocytes.

PMID- 17178587
TI  - ELF non ionizing radiation changes the distribution of the inner chemical
      functional groups in human epithelial cell (HaCaT) culture.
AB  - Human skin cell culture (HaCaT) that has been exposed to an AC magnetic field
      undergoes detectable changes in its biochemical properties and shapes. Such
      changes were observed by infrared wavelength-selective scanning near-field
      optical microscopy with a resolution of 80-100 nm. We specifically investigated
      the changes in the distribution of the inner chemical functional groups and in
      the cell morphology induced by a 24 h exposure to a 1 mT (rms), 50 Hz sinusoidal
      magnetic field in a temperature regulated solenoid. These results further
      accentuate the crucial questions, raised by several recent studies, about the
      impact of low-frequency electromagnetic field on human cells.

PMID- 17178588
TI  - In vivo effects of ELF MFs on collagen synthesis, free radical processes, natural
      antioxidant system, respiratory burst system, immune system activities, and
      electrolytes in the skin, plasma, spleen, lung, kidney, and brain tissues.
AB  - In this study, the results related with the effects of 50 Hz, 0.2 mT-3 mT MFs
      exposures on collagen synthesis, epilepsy, electrolytes, lipid peroxidation
      (MDA), Nitric Oxide (NOx), respiratory burst system (MPO), antioxidant defense
      system (GSH), and immune system (NK cell activity) in spleen, skin, lung, kidney,
      brain, and plasma tissues performed at Gazi Biophysics Department are reviewed.
      Our studies indicate that ELF MFs had effects on the tissues examined.

PMID- 17178589
TI  - Review of in vivo static and ELF electric fields studies performed at Gazi
      Biophysics Department.
AB  - In vivo effects of Static Electric and ELF Magnetic and Electric fields have been
      carried out for more than 20 years in the Bioelectromagnetic Laboratory at the
      Biophysics Department of the Medical Faculty of Gazi University. In this article,
      the results of in vivo ELF Electric field studies are presented as a review.
      Static and 50 Hz ELF (Extremely Low Frequency) Electric (E) fields effects on
      free radical synthesis, antioxidant enzyme level, and collagen synthesis were
      analyzed on tissues of guinea pigs, such as brain, liver, lung, kidney, spleen,
      testis, and plasma. Animals were exposed to static and ELF electric fields with
      intensities ranging from 0.3 kV/m to 1.9 kV/m in vertical and horizontal
      directions. Exposure periods were 1, 3, 5, 7, and 10 days. Electric fields were
      generated from a specially designed parallel plate capacitor system. The results
      indicate that the effects of electric fields on the tissues studied depend
      significantly on the type and magnitude of electric field and exposure period.

PMID- 17178590
TI  - Micro-cells coverage for mobile telephony: an alternative way to reduce EMF
      exposures.
AB  - The aim of this article is to describe networks that are constituted of micro
      cell Based Transceiver Stations (BTS), substituting for the conventional networks
      that are based on the employment of usual macro plants. Specifically, we present
      a micro-cells network designed to substitute for a conventional BTS network, in
      the Don Sturzo Park in the city of Venice, Italy. The lower environmental and
      healthy impact due to a micro-cells network compared to a conventional network is
      discussed.

PMID- 17178591
TI  - Exclusion zones close to wireless communication transmitters aiming to reduce
      human health risks.
AB  - The electromagnetic fields (EMFs) radiated from typical cellular phone
      transmitter stations are calculated and compared to available guidelines
      considering thermal and non thermal biological effects. Exclusion zones close to
      the transmitter station are then estimated. These are three-dimensional figures
      calculated in comparison to a chosen EMF reference human exposure guideline
      limit. The volume inside them represents the regions in which the estimated
      electromagnetic field level is above the limit. Outside the exclusion zone the
      estimated electromagnetic field is below the limits. This procedure can be very
      useful in many applications, e.g., when a transmitter station is expected to be
      placed close to schools, hospitals, or close to areas where people live or work
      and where they spend much time each day. Owing to the uncertainty in science
      regarding the minimum non ionizing radiation level below which no adverse health
      effects can occur, the Precautionary Approach is suggested and it is recommended
      that EMF human exposure be kept to a minimum.

PMID- 17178592
TI  - Electromagnetic absorption in the head of adults and children due to mobile phone
      operation close to the head.
AB  - The Specific Absorption Rate (SAR) produced by mobile phones in the head of
      adults and children is simulated using an algorithm based on the Finite
      Difference Time Domain (FDTD) method. Realistic models of the child and adult
      head are used. The electromagnetic parameters are fitted to these models.
      Comparison also are made with the SAR calculated in the children model when using
      adult human electromagnetic parameters values. Microstrip (or patch) antennas and
      quarter wavelength monopole antennas are used in the simulations. The frequencies
      used to feed the antennas are 1850 MHz and 850 MHz. The SAR results are compared
      with the available international recommendations. It is shown that under similar
      conditions, the 1g-SAR calculated for children is higher than that for the
      adults. When using the 10-year old child model, SAR values higher than 60% than
      those for adults are obtained.

PMID- 17178593
TI  - An analysis of high glucose and glucosamine-induced gene expression and oxidative
      stress in renal mesangial cells.
AB  - Renal mesangial cells play an important role in the development of diabetic
      kidney disease. We have previously demonstrated that some of the effects of high
      glucose on mesangial extracellular matrix (ECM) protein expression are mediated
      by the hexosamine biosynthesis pathway (HBP) in which fructose-6-phosphate is
      converted to glucosamine-6-phosphate by the rate-limiting enzyme
      glutamine:fructose-6-phosphate amidotransferase (GFAT). Using Affymetrix murine
      expression U430 2.0 oligochips, we examined the global effects of high glucose
      (HG) and glucosamine (GlcN) on mRNA expression of a mouse mesangial cell line
      (MES-13). We sought to determine the portion of mRNA expression in MES-13 cells,
      which is mediated both by high glucose and glucosamine, i.e., via the HBP. Of the
      34,000 genes on the chip, approximately 55.7 - 60.8% genes are detected in MES-13
      cells. Culturing MES-13 cells for 48 h with HG alters the expression of
      approximately 389 genes at our preset threshold levels (at least 2-fold change)
      where 263 genes are up-regulated and 126 genes are down-regulated. GlcN also
      increases the expression of 106 genes and decreases 94 genes during the same
      period of incubation. Seventy-two genes in the chip are commonly regulated by HG
      and GlcN, in which 33 genes are up and 39 genes are down. The mRNA level of
      thioredoxin interacting protein (TXNIP), an inhibitor of thioredoxin activity, is
      maximally increased approximately 18.8 and 9.9-fold respectively by HG and GlcN.
      The differential expression of several genes found in the microarray analysis is
      further validated by real-time quantitative PCR. Significant biological processes
      commonly targeted by HG and GlcN are the TXNIP-thioredoxin system, oxidative
      stress, endoplasmic reticulum (ER) stress, extracellular matrix genes, and
      interferon-inducible genes. Stable overexpression of TXNIP in MES-13 cells
      increases glucose and glucosamine-mediated ECM gene expression and oxidative
      stress. We conclude from these results that the HBP mediates several effects of
      high glucose on mesangial cell metabolism, which promotes reactive oxygen species
      generation to cause cellular oxidative stress, ECM gene expression and apoptosis.

PMID- 17178596
TI  - Chemokines: inflammatory mediators of atherosclerosis.
AB  - Atherosclerosis as the underlying mechanisms of myocardial infarction, stroke and
      peripheral artery disease remains the major cause of morbidity and mortality in
      developed countries. Recent developments in vascular biology have indicated that
      atherosclerosis can be best characterized as a chronic inflammatory disease of
      the vessel wall that promotes lesion development and progression. Chemokines
      regulate and control these processes by orchestrating adhesive interactions of
      circulating blood cells with the arterial wall and their subsequent
      extravasation. Exhibiting a high degree of specialization and cooperation,
      different chemokines mediate distinct steps during the atherogenic recruitment of
      monocytes and T cells. This diversity of chemokine expression and function might
      lead to the identification of selective therapeutic targets for the prevention
      and treatment of atherosclerosis.

PMID- 17178597
TI  - Monocyte chemoattractant protein-1--a major contributor to the inflammatory
      process associated with diabetes.
AB  - There is evidence that strongly suggests that inflammation plays an important
      role in diabetes and cardiovascular diseases. The high glucose-induced
      inflammatory process is characterised by the cooperation of a complex network of
      inflammatory molecules such as cytokines, adhesion molecules, growth factors, and
      chemokines. Among the chemokine family, monocyte chemoattractant protein (MCP-1)
      is a potent chemotactic factor, which is upregulated at sites of inflammation
      being in control of leukocytes trafficking. Here, we review the current knowledge
      on MCP-1 and its regulation by high glucose level in vascular cells involved in
      diabetes-induced accelerated atherosclerosis. The signalling pathways involved in
      MCP-1 modulation by high glucose, the proximal signalling events that stimulate
      downstream effects and the role of this chemokine in the pathophysiology of
      diabetes and its complications, are discussed.

PMID- 17178594
TI  - Arrhythmia and neuronal/endothelial myocyte uncoupling in hyperhomocysteinemia.
AB  - Elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) are
      associated with arrhythmogenesis and sudden cardiac death (SCD). Hcy decreases
      constitutive neuronal and endothelial nitric oxide (NO), and cardiac diastolic
      relaxation. Hcy increases the iNOS/NO, peroxynitrite, mitochondrial NADPH
      oxidase, and suppresses superoxide dismutase (SOD) and redoxins. Hcy activates
      matrix metalloproteinase (MMP), disrupts connexin-43 and increases
      collagen/elastin ratio. The disruption of connexin-43 and accumulation of
      collagen (fibrosis) disrupt the normal pattern of cardiac conduction and
      attenuate NO transport from endothelium to myocyte (E-M) causing E-M uncoupling,
      leading to a pro-arrhythmic environment. The goal of this review is to elaborate
      the mechanism of Hcy-mediated iNOS/NO in E-M uncoupling and SCD. It is known that
      Hcy creates arrhythmogenic substrates (i.e. increase in collagen/elastin ratio
      and disruption in connexin-43) and exacerbates heart failure during chronic
      volume overload. Also, Hcy behaves as an agonist to N-methyl-D-aspartate (NMDA,
      an excitatory neurotransmitter) receptor-1, and blockade of NMDA-R1 reduces the
      increase in heart rate-evoked by NMDA-analog and reduces SCD. This review suggest
      that Hcy increases iNOS/NO, superoxide, metalloproteinase activity, and disrupts
      connexin-43, exacerbates endothelial-myocyte uncoupling and cardiac failure
      secondary to inducing NMDA-R1.

PMID- 17178598
TI  - Endothelial cells and macrophages, partners in atherosclerotic plaque
      progression.
AB  - Heart disease and stroke, the main cardiovascular diseases (CVD), have become
      global epidemics in our days. High levels of cholesterol and other abnormal
      lipids are among the main risk factors of atherosclerosis, the number one killer
      in the world. However, recent advances in CVD treatment together with
      improvements in surgical techniques have increased the quality of life and
      reduced premature death rates and disabilities. Nevertheless, they still add a
      heavy burden to the rising global costs of health care. The medical priorities
      highlight not only the need for early recognition of the warning signs of a heart
      attack, but also the need for early biomarkers for prevention. Two active
      partners in the development and progression of atherosclerotic plaques are the
      macrophages and endothelial cells that influence each other and modify the
      microenvironment composition of the plaque leading to either rapid progression or
      regression of individual lesions in patients. In this review we address two
      specific aspects related to atherosclerosis: i) the way in which folic acid and
      folic acid conjugates may be helpful to identify activated macrophages and ii)
      the high potential of proteomic analysis to evidence and identify the multiple
      changes induced in activated vascular cells.

PMID- 17178599
TI  - Role of the fibrinolytic and matrix metalloproteinase systems in development of
      adipose tissue.
AB  - Obesity is a common disorder and related diseases such as diabetes,
      atherosclerosis, hypertension, cardiovascular disease and cancer are a major
      cause of mortality and morbidity in Western-type societies. Development of
      obesity is associated with extensive modifications in adipose tissue involving
      adipogenesis, angiogenesis and extracellular matrix proteolysis. The fibrinolytic
      (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems cooperate in
      these processes. A nutritionally induced obesity model in transgenic mice has
      been used extensively to study the role of the fibrinolytic and MMP systems in
      the development of obesity. These studies support a role of both systems in
      adipogenesis and obesity; the role of specific members of these families,
      however, remains to be determined.

PMID- 17178600
TI  - Can 5-azacytidine convert the adult stem cells into cardiomyocytes? A brief
      overview.
AB  - From the first report that bone marrow cells (BMC) have stem cells
      characteristics, several studies have debated the possibility of intervening in
      myocardial remodeling after injury, for example myocardial infarction, by using
      BMC. The goal of this paper is to review the concept of whether the demethylating
      agent 5-azacytidine influences the myogenic differentiation of bone marrow
      derived cells. The existing data seem to indicate that in vitro treatment with 5
      azacytidine, even if not enough to generate mature CMC, promotes the in vivo and
      in vitro commitment of BMC into cells that express muscle-specific proteins and
      genes and, at a very low rate, show spontaneous contractions. It is probable this
      treatment makes the cells less responsive to other inductive factors secreted by
      the microenvironment that might modulate the differentiation. These data suggest
      that this approach may be used to prime cells prior to their transplantation in
      an injury area in the heart.

PMID- 17178601
TI  - Cellular mechanisms and signalling pathways activated by high glucose and AGE
      albumin in the aortic endothelium.
AB  - This review summarizes evidence on the effect of excess circulating glucose
      concentration and AGE-albumin on the aortic endothelial cells (ECs) phenotype,
      transport function, and expression of signalling molecules. The recent reports on
      the ECs dysfunction in diabetes are briefly reviewed, to provide a broader view
      on the link between ECs structural changes, functional alterations, and the
      underlying biochemical mechanisms. The original results emerging from
      streptozotocin-injected mice and human aortic endothelial cells grown in high (25
      mM) glucose concentration are presented. Compared to physiological condition, in
      diabetes aortic ECs switch to a biosynthetic phenotype, present an increased
      number of caveolae, and enhance (by approximately 20%) transcytosis of AGE
      albumin (AGE-Alb). In cultured ECs, 25 mM glucose induces approximately 2.6 fold
      increase in pSTAT-3 and pERK1 and approximately 1.8 fold increase in pERK2;
      further exposure to 5 microM AGE-Alb causes approximately 4.3 fold increase in
      pERK1/2 (vs. 5 mM glucose). Together, these data may explain the phenotypic
      change, enhanced permeability, and proliferation of aortic ECs in diabetic
      conditions.

PMID- 17178602
TI  - Emerging roles of phosphatidylinositol 3-monophosphate as a dynamic lipid second
      messenger.
AB  - The lipid products of phosphoinositide 3-kinase (PI3K) are involved in many
      cellular responses such as proliferation, migration and survival. Disregulation
      of PI3K-activated pathways is implicated in different disease including diabetes
      and cancer. Among the different products of PI3Ks, phosphatidylinositol-3,4,5
      trisphosphate (PtdIns-3,4,5-P3) has a well established role in signal
      transduction whereas the monophosphate phosphatidylinositol-3-phosphate (PtdIns-3
      P) has been considered for a long time just a cellular component confined in
      endosomal structures. Only recently several evidence have indicated that PtdIns-3
      P can also act as a dynamic intracellular second messenger. The role of PtdIns-3
      P as mediator of crucial intracellular signals is therefore just beginning to be
      appreciated. Here we review some of the latest evidence showing that pools of
      PtdIns-3-P can be generated upon cellular stimulation in compartments different
      from the "classical" endosomal region. We describe several proteins that can be
      targets in mediating signals deriving from such stimulated PtdIns-3-P pools. In
      addition we describe the potential mechanism of switching on and off such
      signals. Taken together all this evidence suggest a novel, key role for PtdIns-3
      P in signal transduction.

PMID- 17178603
TI  - Rehabilitation of endogenous task shift processes in closed head injury patients.
AB  - This paper reports a study that was aimed to rehabilitate executive functions in
      CHI patients. When a subject is engaged in two speeded tasks, not simultaneously
      but with some form of alternation, the response is slower to an item of task A if
      it was preceded by an item of task B, than when it was preceded by an item of
      task A. This shift cost is small when subjects can prepare in advance for the new
      task (endogenous task shift), whereas the cost is much greater when preparation
      is not possible (exogenous task shift). The groups tested comprised 20 severe
      closed head injury (CHI) patients (10 who underwent treatment and 10 controls), 8
      mild CHI patients, and 18 non-brain damaged (NBD) controls. In the present study,
      the shift cost was greater for severe CHI patients than for NBD controls.
      Treatment consisted of five sessions, in which an endogenous task shift paradigm
      was used. A significant reduction of the endogenous shift cost from assessment to
      retest was found. The reduction remained stable at the 4-month follow-up session.
      These results are not simply due to retesting, as the control patients did not
      show any improvement at retest. Interestingly, no reduction of exogenous task
      shift cost was found. The results showed also that the beneficial effect of the
      treatment generalises to other executive functions.

PMID- 17178604
TI  - Topographical disorientation: towards an integrated framework for assessment.
AB  - Topographical disorientation, the inability to find one's way in large-scale
      environments, is a relatively common disorder. However, there are relatively few
      cognitive neuropsychological studies that investigate the nature of topographical
      cognition. Theoretical progress has been hindered by a number of factors
      including: terminological confusion; lack of theoretically driven assessment; the
      use of broad classifications for the nature of underlying impairments; and an
      ongoing failure to examine topographical skills in real-life settings. As a
      result, there is currently no well-established or widely accepted theoretical
      framework encompassing all aspects of this multifaceted area of cognition. In
      addition, there is a relative paucity of published case studies that include a
      comprehensive, theoretically based assessment of topographical disorientation,
      and treatment of the disorder has received virtually no formal investigation
      (with the exception of Davis & Coltheart, 1999). Thus, the current paper focuses
      on the development of a broad framework for understanding topographical cognition
      that integrates a number of recent theories of topographical orientation and
      mental imagery (Farah, 1984; Kosslyn, 1980; Riddoch & Humphreys, 1989). The aim
      of the paper is to present a preliminary framework that can be used as a basis
      for further refinement and development of theoretical proposals, and be employed
      by clinicians as a starting point for assessment planning.

PMID- 17178605
TI  - Assessment and treatment of childhood topographical disorientation: a case study.
AB  - Topographical disorientation refers to individuals who are unable to find their
      way around large-scale environments in a normal manner. Childhood topographical
      disorientation is rarely investigated or reported. Treatment of topographical
      disorientation is also rare with only one reported treatment study in an adult
      (Davis & Coltheart, 1999) and no known description of treatment in a child. This
      paper reports a detailed case analysis of CA, a 6-year-old child with
      topographical disorientation, and a description of a treatment programme focused
      on training orientation in the school environment. Assessment of CA revealed mild
      to moderate visual agnosia in conjunction with severe impairments in general
      spatial learning and memory, topographical new learning and memory, and a total
      inability to learn new topographical routes. CA was also unable to use a mental
      image of his environment, a simple visual plan of his environment or a simple
      visual map, but was able to follow verbally mediated topographical instructions.
      The treatment programme focused on improving CA's topographical orientation in
      the school environment. The programme first involved training in recognition of
      major school buildings and landmarks and then focused on practical training in
      route finding along commonly used routes in the school environment. Clear
      benefits from treatment were evident. The assessment and treatment methods
      employed provide practical and useful ideas for management of this condition in
      other children.

PMID- 17178606
TI  - Spousal relationship satisfaction following acquired brain injury: the role of
      insight and socio-emotional skill.
AB  - Spousal relationships following brain injury are particularly vulnerable to
      strain and breakdown. Changes in personality and socio-emotional processing and
      behaviour have been implicated as causal factors. We examined spousal
      relationship satisfaction following an acquired brain injury to one partner.
      Couples affected by chronic pain and a group of healthy couples were used for
      comparison and control. Compared to healthy controls current satisfaction was
      poorer in the brain injury couples, and satisfaction with the relationship had
      reduced from pre to post-injury. We found an especially important role for
      empathy, which differentiated between the groups in terms of functioning and
      insight.

PMID- 17178607
TI  - Finding out if "The 'me' will shut down": successful cognitive-behavioural
      therapy of seizure-related panic symptoms following subarachnoid haemorrhage: a
      single case report.
AB  - Successful cognitive and behavioural therapies for anxiety disorders in separate
      cases of acquired brain injury and seizure disorder have been reported although
      evidence of efficacy is limited. This paper describes the presentation and
      cognitive-behavioural therapy (CBT) of seizure-related panic symptoms in the
      context of subarachnoid haemorrhage and cavernoma. Multidisciplinary clinical
      assessment was conducted and 12 sessions of CBT according to the model of Clark
      (1986) were delivered. Outcome was measured in terms of goal attainment, belief
      ratings of target cognitions and completion of standardised questionnaire
      measures pre and post-treatment. Process was measured through client's ratings of
      anxiety-related beliefs through treatment. The client attained all goals,
      eliminated avoidance and other unhelpful coping behaviour, and rated reduced
      levels of anxiety on a standardised measure. Changes in identified target
      cognitions were also evident. It is concluded that a cognitive-behavioural
      approach may be helpful in understanding and treating anxiety disorders where
      symptom presentation is complicated by neurological problems. Further
      investigation of the relationship between development of anxiety disorders,
      occurrence of neurological events, and processes of CBT following acquired brain
      injury is suggested.

PMID- 17178610
TI  - Attachment, self-worth, and peer-group functioning in middle childhood.
AB  - We evaluated links between peer-group functioning and indicators of attachment
      security in relation to both mother and father in middle childhood, among 73 10
      year-olds (37 girls). Children's perceptions of security with both parents,
      coping styles with mother, and self-worth were assessed. Classmates, teachers,
      and mothers evaluated the participants' peer-related behavioral characteristics.
      Children's perceptions of security to both parents were related to others'
      appraisals of their social competence; perceptions of security to father were
      related to lower aggression. We did not find child gender effects, but children
      had higher security scores in relation to mother than to father. Self-worth
      perceptions mediated the relation between attachment and social competence.

PMID- 17178609
TI  - DRD4 7-repeat polymorphism moderates the association between maternal unresolved
      loss or trauma and infant disorganization.
AB  - Previous studies have related attachment disorganization in children to either
      dopamine D4 receptor polymorphisms or maternal unresolved loss or trauma and
      frightening or anomalous parenting. In this study it was examined whether the
      interaction between genetic (DRD4 7-repeat and -521 C/T) and environmental risk
      factors (maternal unresolved loss/trauma and maternal frightening behavior) was
      associated with infant disorganization. A moderating role of the DRD4 gene was
      found. Maternal unresolved loss or trauma was associated with infant
      disorganization, but only in the presence of the DRD4 7-repeat polymorphism. The
      increase in risk for disorganization in children with the 7-repeat allele exposed
      to maternal unresolved loss/trauma compared to children without these combined
      risks was 18.8 fold. Similar moderating effects were not found for maternal
      frightening behavior. Our findings indicate that children are differentially
      susceptible to unresolved loss or trauma dependent on the presence of the 7
      repeat DRD4 allele.

PMID- 17178611
TI  - Attachment and psychopathology in a community sample.
AB  - The Structured Clinical Interview for DSM-III-R (SCID-I) and the Adult Attachment
      Interview (AAI) were administered to 60 women participating in a study (n=226) of
      mother-child interaction. These women were not referred to the study for
      psychiatric care. The 60 women interviewed with the AAI were selected from the
      first 190 women who completed the SCID-I, so that 30 received a diagnosis and 30
      did not. Analyses indicated that psychopathology diagnoses were associated
      significantly with mental representations of attachment classified in the AAI.
      The non-autonomous groups had increased likelihood of SCID diagnosis, compared to
      the autonomous group. While 32% of women with autonomous AAI transcripts received
      SCID diagnoses, 63% of women with Dismissing, 100% of woman with Preoccupied, and
      65% of women with Unresolved transcripts received diagnoses. Secondary analyses
      indicated that Dismissing classifications were associated with Axis I diagnoses
      and Preoccupied classifications with affective disorders. Of note was that among
      women with Unresolved classifications, underlying secure attachment was
      associated with low risk of psychopathology, while underlying anxious attachment
      was associated with elevated risk of diagnosis. These findings support the
      premise from attachment theory that early relationships affect patterns of
      interpersonal expectations and behavior and affect regulation.

PMID- 17178612
TI  - The role of adult attachment security in non-romantic, non-attachment-related
      first interactions between same-sex strangers.
AB  - Research using the Adult Attachment Interview has largely examined its predictive
      significance for interpersonal behavior within the context of observations of
      parent-child and romantic relationships. A limitation of this state of affairs is
      that the literature does not make clear whether or when attachment-related
      variation becomes reflected in other kinds of interpersonal encounters. This
      study demonstrates that links between adults' states of mind regarding childhood
      attachment experiences and the quality of their interpersonal interactions are
      evident in first meetings between same-sex strangers in a non-attachment-related
      context. More specifically, in a study of 50 stranger dyads (50% female), secure
      adults demonstrated positive emotional engagement during a challenging puzzle
      building task. In contrast, preoccupied adults dominated the task, whereas
      dismissing adults evidenced negative emotion during the interaction. Results held
      controlling for the Big Five personality dimensions and suggest a middle ground
      position regarding the narrow versus broad correlates of adult attachment
      security.

PMID- 17178613
TI  - The concept of coherence in attachment interviews: comparing attachment experts,
      linguists, and non-experts.
AB  - Coherence is a central construct in attachment interviews. Nevertheless, the
      concept has never been the main focus of a study in the attachment field. The
      present study examined whether coherence in attachment interviews is defined
      differently by experts trained in attachment theory, by linguists, and by non
      experts. The 72-item Coherence Q-sort (CQS) was used to determine the profile of
      a prototypical coherent interview. Results indicated that attachment experts
      could be reliably distinguished from the (combined) other groups: attachment
      experts emphasized quality and manner more than all other groups, linguists
      emphasized quantity and relevance more than attachment experts, and higher
      educated non-experts valued relevance more than attachment experts. Defining
      coherence in attachment interviews is thus more than just applying Grice's
      linguistic maxims; expertise in attachment theory is critical for defining
      interview coherence. Consequences for the coding of the AAI by non-attachment
      experts, as well as computer coding (im)possibilities are discussed.

PMID- 17178614
TI  - Effect of bilateral reaching on affected arm motor control in stroke--with and
      without loading on unaffected arm.
AB  - PURPOSE: To investigate the effect of bilateral reaching, with/without inertial
      loading on the unaffected arm, on hemiparetic arm motor control in stroke.
      METHODS: Twenty unilateral stroke patients were recruited. A three-dimensional
      optical motion capture system was used to measure the movement trajectory of the
      hemiparetic arm while performing three tasks: affected limb reaching forward; two
      limb reaching forward; and two-limb reaching forward with inertia loading of 25%
      upper limb weight on the unaffected limb, respectively. Kinematical parameters
      were utilized to quantify the reaching performance of the affected arm. RESULTS:
      No matter whether loading was applied on the unaffected arm or not, the bilateral
      reaching task did not significantly facilitate smoother and faster movement.
      Furthermore, during bilateral reaching task with/without loading on the
      unaffected arm, stroke patients showed slower movement, lower maximal movement
      velocity, feedback control dominant and discontinuous movements in the affected
      arm than the same task with unilateral reaching. Subjects showed the greatest
      active upper extremity range of motion in proximal joints during the bilateral
      reaching task without unaffected arm loading. The amount of trunk movement also
      increased during bilateral reaching either with or without loading on the
      unaffected arm. Patients with moderate upper extremity motor impairment performed
      more discontinuous movements and less active elbow range of motion during
      bilateral reaching tasks; however, those with mild upper extremity motor
      impairment performed smoother movements and demonstrated greater active elbow
      range of motion during bilateral reaching tasks. CONCLUSIONS: Bilateral reaching
      tasks with/without loading on the unaffected arm could be considered as adding
      challenges during motor control training. Training with bilateral arm movements
      may be considered as a treatment strategy, and can be incorporated in stroke
      rehabilitation to facilitate greater arm active movement and improve motor
      control performance in the affected arm.

PMID- 17178615
TI  - Rehabilitation students' attitudes toward persons with disabilities in high- and
      low-stakes social contexts: A conjoint analysis.
AB  - PURPOSE: The primary objective of this research is to examine factors influencing
      rehabilitation services students' attitudes toward people with disabilities in
      two social contexts using a conjoint analysis design. METHOD: Ninety-nine
      students in rehabilitation counselling participated in a conjoint measurement
      study featuring 55 stimulus cards representing varying disability types, genders,
      races or ethnicities, grade point averages, internship evaluations, and
      employment statuses for both high-stakes scenarios and low-stakes scenarios. The
      participants were instructed to order the stimulus cards to indicate their
      preferences for associating with different people with disabilities in two social
      contexts: A high-stakes context as a rehabilitation administrator hiring a
      counsellor and a low-stakes context as a mentor/companion. RESULTS: The results
      showed that age and disability type were most involved in the decision-making
      process in the low-stakes group, and performance-related variables were most
      important in the high-stakes context. Attitude was significantly affected by
      client characteristics unrelated to disability including age and race or
      ethnicity, and factors influencing attitude formation differed across the two
      social contexts. CONCLUSION: Conjoint analysis can contribute to our
      understanding of the formation of attitudes or preferences in multiple social
      contexts. Using these results, it may be possible to develop effective attitude
      change strategies.

PMID- 17178616
TI  - Reliability and validity of The Awareness of Social Inference Test (TASIT): a
      clinical test of social perception.
AB  - PURPOSE: The Awareness of Social Inference Test (TASIT) is an audiovisual tool
      designed for the clinical assessment of social perception with alternate forms
      for re-testing. Part 1 assesses emotion recognition, Parts 2 and 3 assess the
      ability to interpret conversational remarks meant literally (i.e., sincere
      remarks and lies) or non-literally (i.e., sarcasm) as well as the ability to make
      judgments about the thoughts, intentions and feelings of speakers. This paper
      aims to examine TASIT's reliability and validity. METHOD: Some 32 adults with
      severe, chronic brain injuries were administered Form A twice, one week apart. 38
      adults with brain injuries were readministered alternate forms over a period of 5
      - 26 weeks. Construct validity was examined in subsets of a sample of 116 adults
      with brain injuries by relating TASIT performance to standard tests of
      neuropsychological function and specific social perception measures. RESULTS:
      Test-retest reliability ranged from 0.74 - 0.88. Alternate forms reliability
      ranged from 0.62 - 0.83. TASIT performance was associated with face perception,
      information processing speed and working memory. Socially relevant new learning
      and executive tasks were significantly associated with TASIT performance whereas
      non-social tasks showed little association. Social perception tasks such as Ekman
      photos and theory of mind stories were also associated. CONCLUSIONS: TASIT has
      adequate psychometric properties as a clinical test of social perception. It is
      not overly prone to practice effects and is reliable for repeat administrations.
      Performance on TASIT is affected by information processing speed, working memory,
      new learning and executive functioning, but the uniquely social material that
      comprises the stimuli for TASIT will provide useful insights into the particular
      difficulties people with clinical conditions experience when interpreting complex
      social phenomena.

PMID- 17178617
TI  - Multiple joint pain and lower extremity disability in middle and old age.
AB  - PURPOSE: To determine whether the extent of multiple-site lower extremity joint
      pain contributes to disability in middle and old age and describe patterns of
      severity in site-specific measures amongst those with multiple-site pain. METHOD:
      Population-based, cross-sectional postal survey. Adults aged 50 years and over
      registered with three general practices and reporting pain lasting one month or
      longer in the previous year in at least one hip, knee, or foot were included.
      Respondents completed a generic measure of physical function and site-specific
      measures of severity for each relevant joint pain. RESULTS: Of 2429 eligible
      participants, 1801 reported multiple-site lower limb joint pain. Lower limb joint
      pain count was independently associated with reduced physical function after
      adjusting for a range of covariates. The severity of pain and disability
      attributed to each site increased as the number of painful sites increased.
      CONCLUSION: Many older people with joint pain in the lower limb have more than
      one joint affected. Generic and site-specific measures of disability both show
      the same pattern of reduced physical function. Treatment targeted at a single
      joint may have only a marginal effect on reducing disability in individuals with
      multiple joint involvement unless treatment is also conferring benefit at other
      sites.

PMID- 17178618
TI  - Determination and validity of critical swimming velocity in elite physically
      disabled swimmers.
AB  - The purpose of this investigation was to determine if the critical swimming
      velocity (CSV), defined as the theoretical maximal swimming velocity that could
      be maintained for a long period of time without exhaustion, corresponds to the
      exercise intensity at onset blood lactate accumulation (OBLA), and if it could be
      utilized as a practical index for assessing endurance performance in elite
      physically disabled swimmers. Eight elite physically disabled swimmers swam four
      different distances (50, 100, 200 and 400 m) at maximal effort. The swimming time
      was taken during each trial. The CSV was expressed as the slope of a regression
      line between the covered swimming distance and the corresponding times of all
      possible combinations of 2 or 4 time trials. Results indicate that all the CSVs
      calculated were similar independently of the distances utilized for their
      calculation. Afterwards, a CSV confirmation test consisting of 3 x 10-min trials
      at 95, 100, 105% of the CSV was carried out. The lactate concentration at the end
      of each trial was 3.32, 4.03 and 5.73 mmol x l(-1), respectively. Lactate
      concentration at 100% CSV approached the value of 4 mmol x l(-1), which is
      considered the exercise intensity at OBLA. We conclude that the CSV corresponds
      with the OBLA intensity and could be a valuable index to plan a training schedule
      for physically disabled swimmers.

PMID- 17178619
TI  - Rehabilitation of stroke patients needs a family-centred approach.
AB  - PURPOSE: To highlight the importance of the spouse in stroke rehabilitation.
      Stroke not only affects the patients, but also their families, but rehabilitation
      practice is still primarily focused on the patient only. METHOD: Analysis of the
      position of the spouse and possible consequences of stroke for the spouse, based
      on the literature. RESULTS: Three roles of spouses are described: (i) the role of
      caregiver, as the spouse often provides extensive and comprehensive care for the
      patient; (ii) the role of client, as this informal care may lead to physical and
      emotional strain; and (iii) the role of family member, as the stroke affects the
      interpersonal relationships within the family system, not least the emotional and
      sexual relationship between the partners. This analysis provides an understanding
      of problems experienced by spouses as roles conflict and identifies topics for
      assessment and interventions directed at the spouse in the acute phase,
      rehabilitation phase and chronic phase of stroke. CONCLUSION: We support a family
      centred approach in which the strengths and needs of all family members, the
      patient with stroke included, are considered throughout all phases of the
      rehabilitation process.

PMID- 17178620
TI  - Work physical therapy and rehabilitation ergonomics: a review and discussion of
      the scope of the areas.
AB  - PURPOSE: There has been a recent development of the work physical therapy area in
      Brazil. The relationship between work physical therapy and rehabilitation
      ergonomics needs to be highlighted to avoid segregation and fragmentation of
      these complementary fields. For these reasons, the purpose of this article was to
      review and clarify the scope of the areas of work physical therapy and
      rehabilitation ergonomics. METHOD: The available literature discussing the roles
      of the areas of interest was critically reviewed. RESULTS: Both areas are
      concerned with workers' health and safety and they complement each other.
      CONCLUSIONS: Work physical therapy can be considered as rehabilitation ergonomics
      practiced by physical therapists with their specific interests. Hopefully, this
      paper will contribute to further interaction between the areas of work physical
      therapy and rehabilitation ergonomics not only in Brazil but worldwide. This may
      contribute to improved occupational disability prevention and rehabilitation.

PMID- 17178621
TI  - Technology for improving cognitive function. A workshop sponsored by the US
      Interagency Committee on Disability Research (ICDR): reports from working groups.
AB  - The U.S. federal Interagency Committee on Disability Research (ICDR) and its
      Subcommittee on Technology (IST) sponsored a state of the art workshop on
      "Technology for Improving Cognitive Function", from 29-30 June 2006 in
      Washington, D.C. This paper summarizes the content of the working groups charged
      with providing strategic direction for the future of technology for persons with
      cognitive disabilities.

PMID- 17178623
TI  - Estimation of radiation tolerance to high LET heavy ions in an anhydrobiotic
      insect, Polypedilum vanderplanki.
AB  - PURPOSE: Anhydrobiotic larvae of Polypedilum vanderplanki are known to show an
      extremely high tolerance against a range of stresses. We have recently reported
      that this insect withstands exposure to high doses of gamma-rays (linear energy
      transfer [LET] 0.2 keV/microm). However, its tolerance against high LET radiation
      remains unknown. The aim of this study is to characterize the tolerance to high
      LET radiations of P. vanderplanki. MATERIALS AND METHODS: Larval survival and
      subsequent metamorphoses were compared between anhydrobiotic (dry) and non
      anhydrobiotic (wet) samples after exposure to 1 - 7000 Gy of three types of heavy
      ions delivered from the azimuthally varying field (AVF) cyclotron with LET values
      ranging from 16.2 - 321 keV/microm. The tolerance against 4He ions was also
      compared among three chironomid species. RESULTS: At all LET values measured, dry
      larvae consistently showed greater radiation tolerance than hydrated larvae,
      perhaps due to the presence of high concentrations of the disaccharide trehalose
      in anhydrobiotic animals, and the radiation-induced damage became evident at
      lower doses as development progressed. Relative biological effectiveness (RBE)
      values based on the median inhibitory doses reached a maximum at 116 keV/microm
      (12C), and the maximum RBE clearly increased as development progressed. Lower D0
      (dose to reduce survival from relative value 1.00 - 0.37 on the exponential part
      of the survival curve), and higher Dq (quasi-threshold dose) were found in
      individuals exposed to 4He ions, compared to gamma-rays, and in P. vanderplanki
      larvae compared to non-anhydrobiotic chironomids. CONCLUSION: Anhydrobiosis
      potentiates radiation tolerance in terms of larval survival, pupation and adult
      emergence of P. vanderplanki exposed to high-LET radiations as well as to low-LET
      radiation. P. vanderplanki larvae might have more efficient DNA damage repair
      after radiation than other chironomid species.

PMID- 17178624
TI  - Radiation tolerance in the tardigrade Milnesium tardigradum.
AB  - PURPOSE: Tardigrades are known to survive high doses of ionizing radiation.
      However, there have been no reports about radiation effects in tardigrades under
      culture conditions. In this study, we investigated tolerance of the tardigrade,
      Milnesium tardigradum, against gamma-rays and heavy ions by determining short
      term or long-term survival, and reproductive ability after irradiation. MATERIALS
      AND METHODS: Hydrated and anhydrobiotic animals were exposed to gamma-rays (1000 
      7000 Gy) or heavy ions (1000 - 8000 Gy) to evaluate short-term survival at 2, 24
      and 48 h post-irradiation. Long-term survival and reproduction were observed up
      to 31 days after irradiation with gamma-rays (1000 - 4000 Gy). RESULTS: At 48 h
      after irradiation, median lethal doses were 5000 Gy (gamma-rays) and 6200 Gy
      (heavy ions) in hydrated animals, and 4400 Gy (gamma-rays) and 5200 Gy (heavy
      ions) in anhydrobiotic ones. Gamma-irradiation shortened average life span in a
      dose-dependent manner both in hydrated and anhydrobiotic groups. No irradiated
      animals laid eggs with one exception in which a hydrated animal irradiated with
      2000 Gy of gamma-rays laid 3 eggs, and those eggs failed to hatch, whereas eggs
      produced by non-irradiated animals hatched successfully. CONCLUSION: M.
      tardigradum survives high doses of ionizing radiation in both hydrated and
      anhydrobiotic states, but irradiation with >1000 Gy makes them sterile.

PMID- 17178625
TI  - Cancer risks in a population with prolonged low dose-rate gamma-radiation
      exposure in radiocontaminated buildings, 1983-2002.
AB  - PURPOSE: To assess cancer risks in a population that received prolonged low dose
      rate gamma-irradiation for about 10 years as a result of occupying buildings
      containing 60Co-contaminated steel in Taiwan. MATERIALS AND METHODS: The cancer
      risks were compared with those populations with the same temporal and geographic
      characteristics in Taiwan by standardized incidence ratios (SIR), adjusted for
      age and gender. The association of cancer risks with excess cumulative exposure
      was further evaluated for their relative risks by the Poisson multiple regression
      analysis. RESULT: A total of 7271 people were registered as the exposed
      population, with 101,560 person-years at risk. The average excess cumulative
      exposure was approximately 47.8 mSv (range < 1 - 2,363 mSv). A total of 141
      exposed subjects with various cancers were observed, while 95 developed leukemia
      or solid cancers after more than 2 or 10 years initial residence in contaminated
      buildings respectively. The SIR were significantly higher for all leukemia except
      chronic lymphocytic leukemia (n = 6, SIR = 3.6, 95% confidence interval [CI] 1.2 
      7.4) in men, and marginally significant for thyroid cancers (n = 6, SIR = 2.6,
      95% CI 1.0 - 5.7) in women. On the other hand, all cancers combined, all solid
      cancers combined were shown to exhibit significant exposure-dependent increased
      risks in individuals with the initial exposure before the age of 30, but not
      beyond this age. CONCLUSIONS: The results suggest that prolonged low dose-rate
      radiation exposure appeared to increase risks of developing certain cancers in
      specific subgroups of this population in Taiwan.

PMID- 17178626
TI  - Radiation-induced effects on telomerase in gynecological cancer cell lines with
      different radiosensitivity and repair capacity.
AB  - PURPOSE: Telomerase activation in response to irradiation might enhance the
      radioresistance of cells. Thus, we have investigated radiation-induced effects on
      telomerase in six gynecological cancer cell lines, with different intrinsic
      radiosensitivity and capacity for sublethal damage repair (SLDR). MATERIALS AND
      METHODS: Three endometrial adenocarcinoma (UM-EC-1, UT-EC-2B and UT-EC-3) and
      three vulvar squamous cell carcinoma (A431, UM-SCV-2 and UM-SCV-7) cell lines
      were irradiated with doses of 5, 10 and 25 Gy and the effects on telomerase were
      evaluated at 0.5, 6, 24 and 48 h post-irradiation. Telomerase activity was
      quantitatively measured by SYBR Green real-time telomeric repeat amplification
      protocol. RESULTS: The most radioresistant cell line A431 had the strongest
      stimulatory effects (approximately 2.0 - 2.5-fold) on telomerase activity 24 and
      48 h post-irradiation with the highest radiation doses. In contrast to that,
      telomerase activities in the highly radiosensitive cell line UT-EC-2B remained
      below the basal level throughout the 48-h period of post-irradiation with the
      highest doses, and even a decline to approximately 50% of the basal level was
      found 24 h after exposure. In other cell lines being either moderately or highly
      radiation resistant, telomerase activity levels in response to irradiation
      remained mainly at the basal level or gradually increased. CONCLUSIONS: The
      present findings indicate that there might be a connection between the radiation
      induced telomerase response and radiosensitivity. However, no correlation was
      found between the radiation-induced effects on telomerase and the sublethal
      damage repair capacity of the cells.

PMID- 17178628
TI  - Modulation of chromosome damage localization by DNA replication timing.
AB  - PURPOSE: Non-random occurrence of induced chromosome breakpoints (BP) has been
      repeatedly reported. DNA synthesis and chromatin remodeling may influence
      chromosome BP localization. The CHO9 X chromosome exhibits an early replicating
      short euchromatic arm (Xpe) and a late replicating long heterochromatic arm
      (Xqh). We investigated the role played by DNA replication and related chromatin
      remodeling processes on BP distribution in eu/heterochromatin using the CHO9 X
      chromosome as a model. MATERIALS AND METHODS: BP induced by etoposide, a
      topoisomerase II inhibitor, as well as by the S-dependent clastogens ultraviolet
      C light (UV-C) and methyl methanesulfonate (MMS) were mapped to CHO9 X chromosome
      arms. The base analogue 5-bromo-2'-deoxyuridine (BrdUrd) was pulse-added
      immediately after UV-C irradiation or during etoposide and MMS treatments (40
      min) to identify cells in early S-phase (Xpe labeled) or late S-phase (Xqh
      labeled) after indirect BrdUrd immunodetection in metaphase spreads using primary
      anti-BrdUrd and secondary fluorochrome-tagged antibodies. RESULTS: During early S
      phase, BP induced by etoposide and MMS mapped preferentially to Xpe while BP
      produced by UV-C localized randomly. BP induced by all agents during late S-phase
      clustered in Xqh. CONCLUSIONS: Results obtained suggest that replication time of
      eu/heterochromatin as well as chromatin remodeling may determine BP localization
      on the CHO9 X chromosome.

PMID- 17178627
TI  - Analysis of gamma-rays induced chromosome aberrations: a fingerprint evaluation
      with a combination of pan-centromeric and pan-telomeric probes.
AB  - PURPOSE: To evaluate the types of induced chromosome aberrations after the
      exposure of peripheral blood to gamma-rays by the simultaneous detection of all
      centromeres and telomeres; and to analyse the suitability of different radiation
      fingerprints for the assessment of radiation quality in cases of recent
      exposures. MATERIAL AND METHODS: Peripheral blood samples were irradiated at 2, 4
      and 6 Gy of gamma-rays. Cytogenetic analysis was carried out by fluorescence in
      situ hybridization (FISH) technique with pan-centromeric and peptide nucleic acid
      (PNA)-telomeric DNA probes. Cells were analysed using a Cytovision FISH
      workstation, chromosome aberrations and the length of the acentric fragments were
      recorded. RESULTS: The total number of the incomplete chromosome elements was
      276. The ratio between incomplete elements and multicentrics was 0.38. The number
      of acentrics was 1096, 71% were complete acentrics, 15% incomplete acentrics, and
      14% interstitial fragments. The relative length of complete, incomplete and
      interstitial acentrics fragments were 2.70 +/- 0.04, 1.91 +/- 0.07, and 1.42 +/-
      0.04 respectively. The mean value of the F-ratio was 11.5 higher than the one,
      5.5, previously obtained for alpha-particles. For the G-ratio there was no
      difference between gamma-rays and alpha-particles, 2.8 and 2.8 respectively. The
      mean value of the H-ratio for gamma-rays, 0.25, was lower than for alpha
      particles 0.40. CONCLUSION: The results support that the percentage of incomplete
      chromosome aberrations depends on radiation type; low-linear energy transfer
      (LET) radiation would produces less incomplete aberrations than high-LET
      radiation. The F- and H-ratios seem to be good indicators of radiation quality,
      although a real estimation of the H-ratio is only possible using pan-telomeric
      probes.

PMID- 17178629
TI  - Low doses of ionizing radiation can prevent radiation-induced colonic epithelial
      hyporesponsiveness to muscarinic agonists.
AB  - PURPOSE: Colonic epithelium hyporesponsiveness to different secretagogues occurs
      after exposure to ionizing radiation, increasing susceptibility to bacterial
      translocation and intraluminal toxins. Growing evidence suggests that the
      biological effects of radiation might be hormetic in nature. We investigated if
      exposure to low doses of ionizing radiation (LDR) can prevent colon hyposecretion
      due to subsequent larger doses. METHODS: Rats were exposed to LDR (0.05 Gy) 24 h
      prior to 6 Gy, high dose radiation (HDR). The cyclic adenosine monophosphate
      (cAMP)-mediated pathway was explored using forskolin (FSK) and the intracellular
      Ca2+-mediated pathway through cholinergic stimulation. Changes in the colonic
      epithelium at the ultrastructural level were also explored. RESULTS: Maximal
      short circuit current (Isc) response to carbachol was significantly reduced in
      the group exposed to 6 Gy HDR and this was completely prevented by prior exposure
      to LDR. Responses to both FSK and electrical field stimulation (EFS) were
      significantly reduced after HDR but they were not prevented by prior adaption of
      LDR. Hyposecretion was not prevented by the inducible nitric oxide synthase
      (iNOS) inhibitor L-N6-(l-iminoethyl)lysine (L-NIL) ruling out a role for iNOS
      derived nitric oxide (NO) in the colonic hyposecretion associated with whole body
      radiation. Prior exposure to LDR diminished the deleterious effect of full HDR on
      the ultrastructure of colonic epithelium as colonocytes vacuolization, microvilli
      lost and separation between neighboring cells were less evident. CONCLUSIONS:
      Previous exposure to LDR can prevent intracellular Ca2+-mediated colonic
      hyposecretion associated with exposure to HDR but fails to modify cAMP-mediated
      hyposecretion. Morphological damage at the ultrastructural level is less evident
      after prior LDR.

PMID- 17178630
TI  - Effects of ertiprotafib on hepatic cytochrome P450 and peroxisomal enzymes in
      rats and dogs, and in rat and human primary hepatocytes.
AB  - Ertiprotafib (ERTI) significantly increased liver weights in male and female
      rats, and moderately increased liver weights in male dogs after treatment for 28
      days. The present study tested the hypotheses that the organ weight increases
      were associated with peroxisome proliferation in rats and induction of hepatic
      enzymes in rats and dogs, and would have limited impacts on humans. At a dosage
      of 200 mg kg-1 day-1, CYP4A was induced by tenfold in male rats and 2.4-fold in
      female rats. In male rats, CYP2B was induced by 1.2-fold and CYP3A was induced by
      1.7-fold. Palmitoyl CoA oxidase was induced by 5.1-fold in male rats and 2.9-fold
      in female rats; carnitine acetyltransferase was induced by 10.4-fold in male rats
      and 5.2-fold in female rats. CYP3A, CYP4A and peroxisomal enzymes were not
      induced in dogs at 150/200 mg kg-1 day-1. ERTI at 50 microM markedly induced the
      mRNA level of CYP4A by up to fivefold in rat hepatocytes, but not in human
      primary hepatocytes. In conclusion, the liver weight increases observed in rats
      treated with ERTI appears to be due to rodent-specific peroxisome proliferation
      and the substantial induction of CYP4A1. ERTI is not a potent P450 inducer in
      dogs or in human hepatocytes. Therefore, ERTI is not expected to exert any
      significant effects on hepatic drug-metabolizing enzymes in humans.

PMID- 17178631
TI  - Inhibition and recovery of maternal and foetal cholinesterase enzymes following
      fenitrothion administration in CD rats.
AB  - The purpose of this study was to characterize tissue esterase activity and blood
      fenitrothion concentrations in the rat dam and foetus following in-utero exposure
      to the organophosphate insecticide fenitrothion. Time-mated, 8-week-old rats were
      gavaged on gestation day 19 with 0, 5, or 25 mg fenitrothion kg-1. Fenitrothion
      was absorbed rapidly from the gastrointestinal tract, with peak maternal and
      foetal blood levels observed 0.5-1.0 h after dosing. Fenitrothion concentrations
      in maternal and foetal blood were virtually identical and demonstrated a non
      linear dose-response relationship. Acetylcholinesterase and carboxylesterase
      activities in maternal liver and blood and in foetal liver and brain decreased
      within 30-60 min of fenitrothion exposure. Esterase inhibition occurred at a
      fenitrothion dose (5 mg kg-1) that has not been previously associated with
      reproductive toxicity, suggesting that esterase inhibition should be considered
      as the critical effect in risk assessments for this pesticide.

PMID- 17178632
TI  - CYP2C76-mediated species difference in drug metabolism: a comparison of
      pitavastatin metabolism between monkeys and humans.
AB  - The monkey is often used to predict metabolism of drugs in humans since it
      generally shows a metabolic pattern similar to humans. However, metabolic
      profiles different from humans are occasionally seen in monkeys for some drugs
      including pitavastatin. Recently, we have successfully identified a monkey
      specific cytochrome P450 (CYP) 2C76, which possibly accounts for a species
      difference between monkeys and humans because of its sequence and functional
      uniqueness. The present study on the role of CYP2C76 and other monkey CYP2Cs in
      pitavastatin metabolism, as an example, has revealed that CYP2C76 is important
      for the metabolism of the lactone form, indicating a major role of CYP2C76 for
      the difference in the metabolism of pitavastatin and possibly other drugs between
      monkeys and humans. The current investigation on the involvement of CYP2C76 in
      the metabolism of other drugs is expected to reveal further the further
      importance of this monkey-specific drug-metabolizing enzyme.

PMID- 17178633
TI  - Metabolism of [14C]-5-chloro-1,3-benzodioxol-4-amine in male Wistar-derived rats
      following intraperitoneal administration.
AB  - [14C]-5-chloro-1,3-benzodioxol-4-amine was administered intraperitoneally (i.p.)
      to bile duct-cannulated rats (Alpk:ApfSD, Wistar derived) at 25 mg kg-1 to
      determine the rates and routes of excretion of the compound and to investigate
      its metabolic fate. A total of 89.1% of the dose was excreted in the 48 h
      following administration, the majority being recovered in the urine during the
      first 12 h. The main metabolite in both urine and bile, detected by high
      performance liquid chromatography (HPLC) with radioprofiling and mass
      spectrometry, was identified as a demethylenated monosulfate conjugate. Unchanged
      parent compound formed a major component of the radiolabel excreted in urine and,
      in addition to unchanged parent and demethylenated sulphate conjugate, a large
      number of minor metabolites were detected in urine and bile. The overall
      metabolic fate of 5-chloro-1,3-benzodioxol-4-amine in the rat was complex, with
      some similarities to previously studied methylenedioxyphenyl compounds.

PMID- 17178634
TI  - Stereoselective pharmacokinetics of oxybutynin and N-desethyloxybutynin in vitro
      and in vivo.
AB  - In vitro studies and the multiple applications of an oxybutynin (OXY) transdermal
      delivery system to Japanese healthy volunteers were conducted to characterize the
      stereoselectivity in the pharmacokinetics of OXY and its metabolite, N
      desethyloxybutynin (DEOB). In human liver microsomes, (R)-OXY and (R)-DEOB were
      eliminated slightly slower than the corresponding (S)-enantiomers. The production
      of DEOB from OXY for the (R)-enantiomer was also slower than that for the (S)
      enantiomer. In human P450-expressing liver microsomes, OXY was metabolized mainly
      by CYP3A4 among five cytochrome P450s (CYPs) tested (CYP2C9, CYP2C19, CYP2D6,
      CYP3A4 and CYP3A5) and the kinetics were slightly different for the enantiomer.
      The unbound fraction of (R)-OXY in plasma was almost two times higher than that
      of (S)-OXY, whereas (R)-DEOB was bound to plasma protein more than (S)-DEOB. No
      differences were observed in the blood-plasma concentration ratios for the
      enantiomers. After multiple applications of the transdermal delivery system, the
      plasma concentrations of (R)-OXY were lower than those of (S)-OXY. These data
      indicate that for the stereoselectivity of OXY, the unbound fraction of each OXY
      enantiomer was a major factor and the metabolism in liver had a minimal effect.

PMID- 17178635
TI  - Pharmacokinetic study of darbepoetin alfa: absorption, distribution, and
      excretion after a single intravenous and subcutaneous administration to rats.
AB  - KRN321 is a hyperglycosylated analogue of recombinant human erythropoietin
      (rHuEPO, epoetin alfa), and its absorption, distribution, and excretion have been
      studied after a single intravenous and subcutaneous administration of 125I-KRN321
      at a dose of 0.5 microg kg-1 to male rats. The half-lives of immunoreactive
      radioactivity in the terminal phase after intravenous and subcutaneous
      administration were 14.05 and 14.36 h, respectively, and the bioavailability rate
      after subcutaneous administration was 47%. The total radioactivity in tissues was
      lower than that in the serum in all tissues excluding the thyroid gland and skin
      at the injection site (subcutaneous administration). The maximum concentrations
      were observed in the bone marrow or skin at the injection site followed by the
      thyroid gland, kidneys, adrenal glands, spleen, lungs, stomach and bladder. The
      radioactivity found in trichloroacetic acid-precipitated fractions suggested that
      a high-molecular weight compound, unchanged or mixed with endogenous protein,
      distributed to the tissues after administration. The whole-body autoradiographic
      findings in both groups were in agreement with the tissue distribution mentioned
      above. The blood cell uptake of KRN321 was low for both groups. The excretion
      ratios of radioactivity into urine and faeces up to 168 h were 71.4 and 14.1%
      after the intravenous administration and 74.9 and 12.0% after the subcutaneous
      administration. There was no difference in the excretion profile of radioactivity
      between the two groups.

PMID- 17178636
TI  - Prediction of pharmacokinetics of CS-023 (RO4908463), a novel parenteral
      carbapenem antibiotic, in humans using animal data.
AB  - The pharmacokinetics of CS-023 (RO4908463, formerly R-115685), a novel parenteral
      carbapenem antibiotic, in humans was successfully predicted using the data
      collected from mice, rats, rabbits, and dogs; while inclusion of the monkey data
      led to a significant underestimation of the total plasma clearance (CL). Double
      logarithmic plots of CL and distribution volume at the steady-state (Vss) vs.
      body weight in four animal species were linear with high correlation
      coefficients; and the predicted CL and Vss values in humans agreed well with the
      observed values after administration of CS-023 by an intravenous drip infusion
      for 30 min. The plasma concentration-time profile in humans, which was predicted
      using a bi-exponential equation fitted to a complex Dedrick plot of the animal
      data, approximated the observed profile. An underestimation of CL caused by
      including the monkey data in a prediction is quite likely due to the net tubular
      reabsorption in monkeys, but not at least in rabbits, dogs, and humans.

PMID- 17178637
TI  - Genetic polymorphisms involved in toxicant-metabolizing enzymes and the risk of
      chronic benzene poisoning in Chinese occupationally exposed populations.
AB  - Benzene is a recognized haematotoxin and leukaemogen, but its mechanism of action
      and the role of genetic susceptibility are still unclear. Cytochrome P450 2E1
      (CYP2E1) and myeloperoxidase (MPO) are involved in benzene activation; and NAD
      (P)H:quinine oxidoreductase 1 (NQO1), glutathione S-transferase theta 1 (GSTT1)
      and glutathione S-transferase mu 1 (GSTM1) participate in benzene detoxification.
      The common, well-studied single-nucleotide polymorphisms (SNPs) were analysed in
      these genes drawn from the toxicant-metabolizing pathways. A total of 100 workers
      with chronic benzene poisoning (CBP) and 90 controls were enrolled in China.
      There was a 2.82-fold (95% CI = 1.42-5.58) increased risk of CBP in the subjects
      with the NQO1 609C > T mutation genotype (T/T) compared with those carrying
      heterozygous (C/T) and wild-type (C/C). The subjects with the GSTT1 null genotype
      had a 1.91-fold (95% CI = 1.05-3.45) increased risk of CBP compared with those
      with GSTT1 non-null genotype. There was no association of CYP2E1 and MPO genotype
      with CBP. A three genes' interaction showed that there was a 20.41-fold (95% CI =
      3.79-111.11) increased risk of CBP in subjects with the NQO1 609C > T T/T
      genotype and with the GSTT1 null genotype and the GSTM1 null genotype compared
      with those carrying the NQO1 609C > T C/T and C/C genotype, GSTT1 non-null
      genotype, and GSTM1 non-null genotype. The study provides evidence of an
      association of a gene-gene interaction with the risk of CBP.

PMID- 17178639
TI  - A review of prospective studies of biologic predictors of suicidal behavior in
      mood disorders.
AB  - Predicting suicide is difficult due to the low base rate, even in high-risk
      groups, and the multi-causal nature of suicidal behavior. Clinical predictors
      have shown low specificity. Retrospective and cross-sectional studies have
      identified a number of biologic anomalies associated with suicide and suicide
      attempt. Prospective studies provide estimates of the predictive utility of
      biologic measures. Here we review prospective studies of suicidal behavior and
      serotonergic, noradrenergic, dopaminergic and hypothalamic-pituitary
      adrenocortical axis function in mood disorders. The most promising biologic
      predictors are low CSF 5-HIAA and HPA axis dysfunction as demonstrated by
      dexamethasone non-suppression that are each associated with about 4.5 fold
      greater risk of suicide.

PMID- 17178640
TI  - Molecular genetic findings in suicidal behavior: what is beyond the serotonergic
      system?
AB  - Various studies provide consistent evidence for a genetic component in suicidal
      behavior. First molecular genetic studies concentrated on genes of the
      serotonergic system based on the biochemical evidence that serotonergic
      neurotransmission is implicated in this behavior. Furthermore, genes of the
      dopaminergic and noradrenergic neurotransmitter systems have also been the
      subjects of investigations in this context. Some epidemical and clinical studies
      showed that low serum cholesterol levels are associated with suicidal behavior
      and genes involved in these pathways have been investigated. Microarray
      experiments provide the possibility of genome-wide gene expression analysis and
      help to investigate associated molecular mechanisms. The aim of this article is
      to review molecular genetic studies in suicidal behavior and to emphasize
      findings on new genes.

PMID- 17178641
TI  - An analysis of suicidal ideation in a college sample.
AB  - Two studies were designed to develop and validate a model of current suicidal
      ideation. In Study 1, students that reported past suicide attempts (n = 48) were
      compared to controls (n = 49) on nine variables previously linked to suicidal
      behavior. In the resulting model, borderline personality characteristics and
      social support were found to correlate with current suicidal ideation, supporting
      a mediating model. In Study 2, the Borderline/Social Support (BTSS) model was
      validated in an independent sample. Implications for risk assessment, prevention
      and treatment of suicidal college students are discussed.

PMID- 17178642
TI  - Suicide rates in the Lundby cohort before and after the introduction of tricyclic
      antidepressant drugs.
AB  - The Lundby cohort consisting of 3563 subjects was investigated in 1947, 1957,
      1972, and 1997. It represents a rural, but gradually urbanized Swedish sample
      without non-Nordic immigrants and offers an opportunity to study suicide rates
      before and after the introduction of tricyclic antidepressant drugs in Sweden in
      1962. Since then, a fall in suicide rate among depressed individuals was
      observed, while there was an increase in the overall suicide rate. In fact, in
      1977-1992 other psychiatric diagnoses, alcohol disorder included, were more often
      associated with suicide than depression. No psychiatric or alcohol disorder was
      registered in 7% of the suicides.

PMID- 17178643
TI  - Risk for suicide attempts among adolescents who engage in non-suicidal self
      injury.
AB  - The current study examined whether common indicators of suicide risk differ
      between adolescents engaging in non-suicidal self-injury (NSSI) who have and have
      not attempted suicide in an effort to enhance clinicians' ability to evaluate
      risk for suicide within this group. Data were collected from 540 high school
      students in the Midwest who completed the RADS, RFL-A, SIQ, and SHBQ as part of a
      larger adolescent risk project. Results suggest that adolescents engaging in NSSI
      who also attempt suicide can be differentiated from adolescents who only engage
      in NSSI on measures of suicidal ideation, reasons for living, and depression.
      Clinical implications of the findings are discussed.

PMID- 17178644
TI  - Cluster C personality disorders in major depressive episodes: the relationship
      between hostility and suicidal behavior.
AB  - There is some evidence for an association between Cluster C Personality Disorders
      (CCPD) and suicidal behavior. We compared depressed inpatients with and without
      CCPD in terms of suicidal behavior and associated psychopathology. Cluster A or B
      personality disorder co-morbidity were exclusion criteria for both groups (cases
      and controls). Depressed inpatients with "pure" CCPD had higher levels of
      suicidal ideation but not more previous suicide attempts compared with patients
      without CCPD. Greater suicidal ideation in depressed patients with CCPD in our
      study was associated with more hostility. Future studies examining the
      relationship between suicidal ideation and hostility in CCPD may clarify whether
      treatment focused on hostility might be of use for decreasing suicidal ideation
      in depressed patients with CCPD (Spitzer, Williams, Gibbon et al., 1990).

PMID- 17178645
TI  - Characteristics of recent suicide attempters with and without Borderline
      Personality Disorder.
AB  - The present research compared recent suicide attempters with and without a
      diagnosis of Borderline Personality Disorder (BPD). One hundred and eighty recent
      suicide attempters, recruited in the Emergency Department, participated in
      extensive research interviews. Results showed that suicide attempters with BPD
      displayed greater severity of overall psychopathology, depression, hopelessness,
      suicidal ideation, past suicide attempts, and had poorer social problem solving
      skills than those without a BPD diagnosis. No differences were found between the
      groups regarding the intent to die or lethality associated with the index suicide
      attempt. These findings highlight the seriousness of BPD and the risk that
      individuals diagnosed with this disorder will attempt suicide.

PMID- 17178646
TI  - Correlates of suicide in building industry workers.
AB  - Suicide within the construction industry in Queensland, Australia was reportedly
      high in a recent Royal Commission report. The current study examined the
      incidence and causes of suicide in this industry using psychological autopsy and
      focus group investigations. A total of 64 male suicides occurred over the seven
      year period, representing a crude suicide rate of 40.3 per 100,000, significantly
      greater than the working age Australian male rate. Young employees were at
      excessive risk with separation/divorce, relationship problems, and untreated
      psychiatric conditions the major contributors. Focus groups emphasized the
      importance of work/home interface factors and industry-specific factors preceding
      suicide.

PMID- 17178649
TI  - The Work Compatibility Improvement Framework: an integrated perspective of the
      human-at-work system.
AB  - The industrial revolution demonstrated the limitations of a pure mechanistic
      approach towards work design. Human work is now seen as a complex entity that
      involves different scientific branches and blurs the line between mental and
      physical activities. Job design has been a traditional concern of applied
      psychology, which has provided insight into the interaction between the
      individual and the work environment. The goal of this paper is to introduce the
      human-at-work system as a holistic approach to organizational design. It
      postulates that the well-being of workers and work outcomes are issues that need
      to be addressed jointly, moving beyond traditional concepts of job satisfaction
      and work stress. The work compatibility model (WCM) is introduced as an
      engineering approach that seeks to integrate previous constructs of job and
      organizational design. The WCM seeks a balance between energy expenditure and
      replenishment. The implementation of the WCM in industrial settings is described
      within the context of the Work Compatibility Improvement Framework. A sample
      review of six models (motivation-hygiene theory; job characteristics theory;
      person-environment fit; demand-control model; and balance theory) provides the
      foundation for the interaction between the individual and the work environment. A
      review of three workload assessment methods (position analysis questionnaire, job
      task analysis and NASA task load index) gives an example of the foundation for
      the taxonomy of work environment domains. Previous models have sought to identify
      a balance state for the human-at-work system. They differentiated between the
      objective and subjective effects of the environment and the worker. An imbalance
      between the person and the environment has been proven to increase health risks.
      The WCM works with a taxonomy of 12 work domains classified in terms of the
      direct (acting) or indirect (experienced) effect on the worker. In terms of
      measurement, two quantitative methods are proposed to measure the state of the
      system. The first method introduced by Abdallah et al. (2004) identifies
      operating zones. The second method introduced by Salem et al. (2006) identifies
      the distribution of the work elements on the x/y coordinate plane. While previous
      efforts have identified some relevant elements of the systems, they failed to
      provide a holistic, quantitative approach combining organizational and human
      factors into a common framework. It is postulated that improving the well-being
      of workers will simultaneously improve organizational outcomes. The WCM moves
      beyond previous models by providing a hierarchical structure of work domains and
      a combination of methods to diagnose any organizational setting. The WCM is an
      attempt to achieve organizational excellence in human resource management, moving
      beyond job design to an integrated improvement strategy. A joint approach to
      organizational and job design will not only result in decreased prevalence of
      health risks, but in enhanced organizational effectiveness as well. The
      implementation of the WCM, that is, the Work Compatibility Improvement Framework,
      provides the basis for integrating different elements of the work environment
      into a single reliable construct. An improvement framework is essential to ensure
      that the measures of the WCM result in a system that is adaptive and self
      regulated.

PMID- 17178647
TI  - Correlates of lifetime suicide attempts among individuals with affective
      disorders in a Chinese rural community.
AB  - The aim of this study was to compare the demographic and clinical characteristics
      of individuals with affective disorders who had attempted suicide at some time in
      their lives and those who had not made a suicide attempt. In a Chinese rural
      community, individuals with suicide attempt (N = 30) and those without suicide
      attempt (N = 166) were assessed with Present State Examination (PSE). Attempters
      had a significantly higher level of family economic status, higher rate of
      lifetime depressed mood and hopelessness, and delusions than nonattempters. The
      logistic regression models also indicated that depressed mood and hopelessness
      were the most important predictors of suicide attempts. No significant difference
      in treatment condition was found between attempters and non-attempters. Early
      identification and interventions focusing on reducing depressed mood,
      hopelessness, and controlling psychotic symptoms may be helpful in reducing the
      risk of suicide attempts among individuals with affective disorders residing in
      the community.

PMID- 17178650
TI  - The influence of age on isometric endurance and fatigue is muscle dependent: a
      study of shoulder abduction and torso extension.
AB  - The present study examined differences in isometric muscle capacity between older
      (55-65 years) and younger (18 - 25 years) individuals. A total of 24 younger and
      24 older participants (gender balanced within each group) performed sustained
      shoulder abductions and torso extensions to exhaustion at 30%, 50% and 70% of
      individual maximal voluntary contraction (MVC). Along with endurance time,
      manifestations of localized fatigue were determined based on changes in surface
      electromyographic signals obtained from the shoulder (middle deltoid) and the
      torso (multifidus and longissimus thoracis) muscles. Strength recovery was
      monitored using post-fatigue MVCs over a 15-min period. Compared to the younger
      group, older individuals exhibited lower muscular strength, longer endurance time
      and slower development of local fatigue. Age effects on fatigue were typically
      moderated by effort level, while effects of gender appeared to be marginal. Non
      linear relationships between target joint torque and endurance time were
      observed, with effects of age differing between shoulder abduction and torso
      extension. Overall, the effects of age on endurance and fatigue were more
      substantial and more consistent for the shoulder muscle than for the torso
      muscles and were likely related to differences in muscle fibre type composition.
      For strength recovery rates, no significant age or gender effects were found in
      either experiment. In summary, this study suggests that differences in isometric
      work capacity do exist between older and younger individuals, but that this
      effect is influenced by effort level and the muscle tested.

PMID- 17178651
TI  - Back to the future: brake reaction times for manual and automated vehicles.
AB  - Rear-end collisions are often quoted as being a major cause of road traffic
      accidents. In response to this, a great deal of ergonomics research effort has
      been directed towards the analysis of brake reaction times. However, the
      engineering solution has been to develop advanced systems for longitudinal
      control, which, it is argued, will mitigate the problem of rear-end collisions.
      So far, though, there have been few empirical studies to determine how brake
      reaction times will be affected by such vehicle automation. This paper presents a
      literature review summarizing the current state of knowledge about driver
      responses in non-automated vehicles. The review covers driver factors, vehicle
      factors and situational factors. Following the review, some empirical data are
      presented from a driving simulator experiment assessing brake reaction times of
      skilled and unskilled drivers under two different levels of automation. When
      compared to previous data gathered during manual driving, there seems to be a
      striking increase in reaction times for these automated conditions. Implications
      for the design and safety of automated vehicle systems are discussed.

PMID- 17178653
TI  - Effect of wearing personal protective clothing and self-contained breathing
      apparatus on heart rate, temperature and oxygen consumption during stepping
      exercise and live fire training exercises.
AB  - Fire fighter breathing apparatus instructors (BAIs) must possess the ability to
      respond to both the extrinsic stress of a high temperature environment and the
      intrinsic stress from wearing personal protective equipment (PPE) and self
      contained breathing apparatus (SCBA), repeatedly and regularly, whilst training
      recruits in live fire training exercises (LFTEs). There are few previous
      investigations on BAIs in hot environments such as LFTEs, since the main research
      focus has been on regular fire fighters undertaking exercises in temperate or
      fire conditions at a moderate to high exercise intensity. In this study, the
      intrinsic cardiovascular stress effects of wearing PPE + SCBA were first
      investigated using a step test whilst wearing gym kit (control), weighted gym kit
      (a rucksack weighted to the equivalent of PPE + SCBA) and full PPE + SCBA (weight
      plus the effects of protective clothing). The extrinsic effects of the very hot
      environment were investigated in BIAs in LFTEs compared to mock fire training
      exercises (MFTEs), where the fire was not ignited. There was an increase in heart
      rate due to the modest workload imposed on the BAIs through carrying out the
      MFTEs (25.0 (18.7)%) compared to resting. However, when exposed to fire during
      the LFTEs, heat storage appears to be significant as the heart rate increased by
      up to 39.8 (+/-20.1)% over that of the mock LFTEs at temperate conditions. Thus,
      being able to dissipate heat from the PPE is particularly important in reducing
      the cardiovascular responses for BAIs during LFTEs.

PMID- 17178652
TI  - Progress in understanding processes underlying occupational accidents on the
      level based on case studies.
AB  - The purpose of this work was to further the knowledge of contexts surrounding
      accidents on the level in occupational situations with a view to proposing
      suitable actions for the prevention of these accidents. The study, undertaken at
      three establishments belonging to a national rail transport company, was based on
      quantitative and qualitative analysis of accident-on-the-level data available at
      the establishments concerned, typology of these accidents, interviews with
      victims and activity analysis. Understanding accidents on the level through
      building scenarios makes it possible to consider the relevance of prevention
      actions, such as workplace or environmental design/remediation and machine access
      system design. Moreover, it also makes it possible to consider curtailing the
      injury-causing aspect of the physical environment by reducing its
      'aggressiveness'. Finally, the prospects emerging from this work in the research
      field are discussed.

PMID- 17178654
TI  - Applicability of location compatibility to the arrangement of display and control
      in human - vehicle systems: comparison between young and older adults.
AB  - The effects of age on applicability of the location compatibility principle to
      the design of display and control systems were discussed. A dual-task experiment
      was conducted, in which the primary task was first-order tracking. The secondary
      tasks included control of an air conditioner, the operation of a radio and the
      operation of a CD/MD, by means of either a steering wheel-mounted switch or a
      console-mounted switch. The display was arranged either in front of or on the
      left side of a participant. Performance of the young group did not completely
      follow predictions of the compatibility principle. In particular, the principle
      did not apply to the left-side display condition. The steering wheel-mounted
      switch was more effective than the left-side switch even for the left-side
      display. The compatibility principle was applicable to both front and left-side
      displays for the older adults. For the front display, the steering wheel-mounted
      switch was more effective. Such differences should be taken into account when
      designing display and control systems in man - vehicle systems.

PMID- 17178655
TI  - Effects of conflict alerting system reliability and task difficulty on pilots'
      conflict detection with cockpit display of traffic information.
AB  - A total of 24 pilots viewed dynamic encounters between their own aircraft and an
      intruder aircraft on a 2-D cockpit display of traffic information (CDTI) and
      estimated the point and time of closest approach. A three-level alerting system
      provided a correct categorical estimate of the projected miss distance on 83% of
      the trials. The remaining 17% of alerts were equally divided between misses and
      false alarms, of large and small magnitude. Roughly half the pilots depended on
      automation to improve estimation of miss distance relative to the baseline
      pilots, who viewed identical trials without the aid of automated alerts.
      Moreover, they did so more on the more difficult traffic trials resulting in
      improved performance on the 83% correct automation trials without causing harm on
      the 17% automation-error trials, compared to the baseline group. The automated
      alerts appeared to lead pilots to inspect the raw data more closely. While
      assisting the accurate prediction of miss distance, the automation led to an
      underestimate of the time remaining until the point of closest approach. The
      results point to the benefits of even imperfect automation in the strategic
      alerts characteristic of the CDTI, at least as long as this reliability remains
      high (above 80%).

PMID- 17178656
TI  - The inadequate effect of automobile seating on foot posture and callus
      development.
AB  - Driver posture is an important factor to be considered in the ergonomics design
      process of automobiles. Most decisions during automobile design and manufacture
      are informed by studying the intricate biomechanical components of human
      musculoskeletal systems to ensure maximum comfort, safety and well-being during
      driving. A case study is presented that confirms inappropriate foot position as a
      causative factor for the development of abnormal lateral/plantar heel callosities
      when driving a 4 x 4-style vehicle. The driver's foot position was influenced by
      the seat geometry of the vehicle. Cessation of driving the 4 x 4-style vehicle
      and driving of an alternative automobile while on holiday for a period of 4 weeks
      resolved the condition. On return to the 4 x 4-style vehicle, however, the
      abnormal callus patterns redeveloped while using the same footwear and no change
      in any other parameters. It is therefore suggested that seat and consequent foot
      position is an important ergonomic factor that should be addressed in the future
      design of automobile seating.

PMID- 17178659
TI  - Advances in the diagnosis and management of von Willebrand disease.
AB  - von Willebrand disease (VWD), the most common inherited bleeding disorder, is
      caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of von
      Willebrand factor (VWF). In this review, the present knowledge regarding the
      diagnosis and the management of VWD is briefly analyzed.

PMID- 17178657
TI  - Violations and errors during simulation-based driver training.
AB  - The effectiveness of virtual driving instruction can increase when techniques
      that automatically distinguish between violations and errors are available, two
      behaviours requiring different types of remediation. This study reports the
      analysis of the objectively measured performance of 520 participants completing a
      simulation-based training programme. Factor analysis of failure reasons showed
      that violations and errors were the primary underlying factors. Men committed
      more violations and women made more errors; the magnitude of sex differences
      corresponded to the factor loadings. Factor analysis of the mean task completion
      times yielded a factor that can be described as the extent to which motivation
      for speed resulted in quicker task execution. Quicker participants completed more
      tasks, committed more violations, but made fewer errors. Participants reduced
      errors during forced-paced driving and increased speed during self-paced driving.
      The authors would recommend exploiting the distinction between violations and
      errors by developing interfaces and feedback for both types of aberration.

PMID- 17178660
TI  - Impact of CD31 mismatches on the outcome of hematopoeitic stem cell transplant of
      HLA-identical sibling.
AB  - Graft-versus host disease (GVHD) complicating allogeneic hematopoeitic stem cell
      transplantation (HSCT) is often attributed to mismatching of minor
      histocompatibility antigens (mHags), which are poorly defined in humans. CD31 is
      a candidate human mHag relevant to acute GVHD (aGVHD), but reports disagree about
      its level of significance. Therefore, we examined the impact of CD31-matching on
      the outcome of HSCT in different hematological and immunological diseases. About
      60 patients receiving HSC from their respective HLA-ABCDR and DQ-identical
      sibling were studied. DNA was used to study the CD31 allele polymorphism at the
      codon 125 (LL, LV or VV) in the patient-donor pairs using the principle of allele
      specific PCR amplification. Four primer were used; two primers (forward and
      reverse) for the L allele and another two for the V allele. The CD31 identity was
      tested for correlation with HSCT outcome measures of aGVHD, chronic GVHD, and
      relapse. The gene frequency of CD31 alleles (LL, VV and LV) was 28.3, 20 and
      51.7%, respectively. CD31 identity was found in 31 pairs (51.7%) versus 29 pairs
      (48.3%) for nonidentity. The CD31 noncompatibility showed statistical non
      significant relation with aGVHD (G 0-I, and G II-IV) and chronic GVHD (De-novo
      and chronic on acute) (p = 0.59, p = 0.62, p = 036 and p = 0.83, respectively).
      The CD31 nonidentity had statistical significant relation with aGVHD versus no
      aGVHD (p = 0.008 and OR = 4.46). The CD31 nonidentity showed statistical
      significant relation with aGVHD (II-IV) versus no aGVHD (p = 0.012 and OR = 7.14)
      and also, aGVHD (0-I) versus the no aGVHD (p = 0.03, OR = 3.13, respectively). A
      statistical significant relation was found between CD31 nonidentity in patient
      donor pairs and relapse (p = 0.014 and OR = 4.21). In conclusion, the donor
      recipient CD31 nonidentity is a significant risk factor for aGVHD and relapse in
      HLA-identical sibling.

PMID- 17178661
TI  - t(8;21) (q22;q22) acute myelogenous leukemia in Mexico: a single institution
      experience.
AB  - We analyze the prevalence and clinical features of a group of patients with
      t(8;21) (q22;q22) acute myeloblastic leukemia, identified in a single institution
      in Mexico over a 10-year period. Fifteen patients presented at the Centro de
      Hematologia y Medicina Interna de Puebla from February 1995 to August 2005; only
      nine were treated and followed in the institution. Median age was 24 years,
      (range 7-49); there was only one male. According to the French-American-British
      (FAB) morphological classification of leukemia, the morphology was M2 in four
      cases, M4 in three cases, M3 in one case and M0 in one. In addition to the
      myeloid markers, lymphoid markers were identified in 6 patients. Patients were
      induced to remission with combined chemotherapy and three subsequently underwent
      bone marrow transplantation (BMT). The median overall and disease-free survival
      has not been reached, being above 3390 days, the probability of survival at this
      time was 73%. In this single-center experience in Mexico, we found that the
      t(8;21) (q22;q22) variant of leukemia was more frequent than in Caucasian
      populations, that the co-expression of lymphoid markers in the blast cells is
      very frequent and that this malignancy is associated with a relatively good
      prognosis.

PMID- 17178662
TI  - Increased serum lactate dehydrogenase isoenzymes in Ph-negative chronic
      myeloproliferative diseases: a metabolic adaptation?
AB  - We evaluated the significance of lactate dehydrogenase (LDH) isoenzymes in
      chronic myeloproliferative disorders (CMDs) by studying LDH isoenzymes in the
      serum of patients with secondary polycythemia (SP), polycythemia vera (PV),
      essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) in different
      disease status. LDH activity and isoenzymes were evaluated retrospectively in
      serum samples from four groups of patients and compared with a control group. LDH
      activity and isoenzyme distributions of patients with SP and PV did not reveal
      significant variations with respect to controls. In the ET and IMF group LDH
      isoenzyme revealed significant variations: IMF showed significant increase of
      LDH2 and significant reduction of LDH5 isoenzyme, whereas ET showed significant
      decrease in LDH1 and increase of LDH3. These data suggest that LDH isoenzyme
      patterns may be a useful marker of CMDs, but this enzymatic pattern could be
      expression of a metabolic adaptation.

PMID- 17178663
TI  - T-large granular lymphocyte leukemia: current molecular concepts.
AB  - T-large granular lymphocyte (T-LGL) leukemia is a chronic and often indolent T
      cell lymphoproliferation characterized by extreme expansion of a semi-autonomous
      cytotoxic T lymphocyte (CTL) clone. Clinically, T-LGL can be associated with
      various cytopenias; neutropenia constitutes the most frequent manifestation. LGL
      clone represents a pathologic counterpart of the cytotoxic effector T cell but an
      abnormal memory CD8 cell seems to provide the supply of the matured LGL
      population. Analysis of clonal T cell receptor (TCR) rearrangement and
      complementarity determining region 3 (CDR3) of the TCR beta-chain is a useful
      tool to investigate clonal expansions, track the frequency of expanded clones and
      also clinically useful to monitor the response to therapy. The lessons learned
      from molecular analysis of clonal repertoire support a clinically-derived
      conclusion that the LGL clone arises in the context of an initially polyclonal
      immune response or an autoimmune process. Consequently, specific manifestations
      of T-LGL may be a result of the recognition spectrum of the transformed clone and
      the cytokines it produces. Due to the often monoclonal manifestation, T-LGL
      constitutes a suitable model to investigate polyclonal CTL-mediated processes.
      Application of new technologies, including TCR repertoire analysis by sequencing,
      clonotypic quantitative PCR and VB flow cytometry facilitate clinical diagnosis
      and may allow insights into the regulation of TCR repertoire and consequences
      resulting from the contraction of clonal diversity.

PMID- 17178664
TI  - Parvovirus B-19 induced acute pure red cell aplasia in patients with chronic
      lymphocytic leukemia and neurofibromatosis type-1.
AB  - Parvovirus B19 induced pure red cell aplasia (PRCA) has been previously reported
      in a variety of settings. We present two cases, an adult patient with chronic
      lymphocytic leukemia (CLL) and a child with neurofibromatosis type-1 (NF-1),
      where the abrupt appearance of severe anemia raised ominous clinical suspicions.
      Evidence of recent parvovirus B19 infection in association with the selective
      erythroid precursor deficiency in marrow helped exclude other etiologies. We
      emphasize the importance of bearing this infectious agent in mind, even when
      there are associated disorders (such as CLL) that may independently cause PRCA.
      An association of NF-1 with acute PRCA has not been described in indexed English
      literature in the past.

PMID- 17178665
TI  - Parvovirus B19 infection in children with a variety of hematological disorders.
AB  - This study was carried out to detect Parvovirus B19 (PB19) DNA together with its
      antibodies in the sera of children with a range of hematological disorders to
      clarify the contribution of this infection to changes observed in hematological
      picture in those populations. This study included 85 pediatric patients with
      different hematological disorders. Twenty healthy subjects with matched age and
      sex were included as controls. Patients were classified into four groups; group I
      included 25 patients with hemolytic anemia in aplastic crisis, group II included
      20 patients with hemolytic anemia without aplastic crisis, group III included 20
      acute leukemia patients under chemotherapy, group IV included 20 patients with
      recently diagnosed acute leukemia. Virological study for PB19 included
      determination of specific IgG & IgM together with viral DNA by polymerase chain
      reaction (PCR). In all groups of patients with positive markers for PB19, there
      were statistically significant differences in the mean Hb concentration and RBC
      count (P < 0.001 for each), presence of neutropenia (P = 0.003) and lymphocytosis
      (P < 0.001) compared to controls. There was statistically significant difference
      in the prevalence of PB19 IgM, IgG and PCR among studied groups compared to
      control group. In group I and group II IgG had the highest positive rate (56 and
      35%, respectively). In group III IgG also had a high positive rate (45%).
      However, in group IV IgM had the highest positive rate (50%) followed by PCR
      (45%) then IgG (40%). In conclusion, PB19 infection is detected in high rates
      among children with hematological disorders. PB19 must be suspected and screened
      for when there is anemia in those patients associated with neutropenia and
      lymphocytosis. In patients with acute leukaemia under chemotherapy who have
      unexpected anemia, neutropenia and lymphocytosis Parvovirus infection should be
      considered before a change of chemotherapy protocol. Screening of blood for PB19
      may be helpful in understanding the epidemiology of infection with this virus.
      The direct detection of DNA by PCR in sera needs to be coupled with serology for
      a more reliable diagnosis of PB19 infections in these children.

PMID- 17178666
TI  - Multiply relapsing hairy cell leukemia responsive to repeated courses of
      rituximab: a case report.
AB  - While cladribine is a highly effective therapy for patients with symptomatic
      hairy cell leukemia (HCL), up to 37% of patients ultimately relapse and
      incompletely responding patients relapse more frequently. Rituximab is a
      monoclonal antibody against CD20 that has been shown to be effective in patients
      with relapsed HCL. We present an unusual case of successful multiple re
      treatments with rituximab in a patient with heavily pre-treated HCL and briefly
      review the relevant literature.

PMID- 17178667
TI  - Molecular pathogenesis and clinical variability of homozygous beta0-thalassemia
      in populations of Jammu region of J&K state (India).
AB  - This study was undertaken to evaluate the variation in the clinical presentation
      of homozygous beta0-thalassemia from severe disease to a beta-thalassemia
      intermedia phenotype and to look for the contribution of associated factors in
      this variation of clinical course. Type of beta0-thalassemia mutations,
      associated alpha-thalassemia, and XmnI polymorphism in the gamma globin gene,
      which are known to affect the clinical course of the disease, were investigated
      from 15 homozygous beta0-thalassemia patients comprising 11 patients with beta
      thalassemia major and 4 patients with beta-thalassemia intermedia. Transfusion
      dependency and the age at which the patient presented with symptoms were used to
      assess the degree of clinical severity of these patients. Three different beta0
      thalassemia mutations viz. CD 41-42 (-TTCT), CD 8-9 (+G) and 619 bp deletion,
      were encountered among the 30 beta-thalassemia alleles. It was observed that the
      type of beta0-thalassemia mutations was not different between the two groups, but
      co-inheritance of one or more alpha-gene deletions and the presence of the XmnI
      polymorphism were associated with lesser severity of the disease.

PMID- 17178668
TI  - Bias-corrected diagnostic performance of the naked-eye single-tube red-cell
      osmotic fragility test (NESTROFT): an effective screening tool for beta
      thalassemia.
AB  - It is being increasingly recognized that a majority of the countries in the
      thalassemia-belt need a cost-effective screening program as the first step
      towards control of thalassemia. Although the naked eye single tube red cell
      osmotic fragility test (NESTROFT) has been considered to be a very effective
      screening tool for beta-thalassemia trait, assessment of its diagnostic
      performance has been affected with the reference test- and verification-bias.
      Here, we set out to provide estimates of sensitivity and specificity of NESTROFT
      corrected for these potential biases. We conducted a cross-sectional diagnostic
      test evaluation study using data from 1563 subjects from Central India with a
      high prevalence of beta-thalassemia. We used latent class modelling after
      ensuring its validity to account for the reference test bias and global
      sensitivity analysis to control the verification bias. We also compared the
      results of latent class modelling with those of five discriminant indexes. We
      observed that across a range of cut-offs for the mean corpuscular volume (MCV)
      and the hemoglobin A2 (HbA2) concentration the average sensitivity and
      specificity of NESTROFT obtained from latent class modelling was 99.8 and 83.7%,
      respectively. These estimates were comparable to those characterizing the
      diagnostic performance of HbA2, which is considered by many as the reference test
      to detect beta-thalassemia. After correction for the verification bias these
      estimates were 93.4 and 97.2%, respectively. Combined with the inexpensive and
      quick disposition of NESTROFT, these results strongly support its candidature as
      a screening tool-especially in the resource-poor and high-prevalence settings.

PMID- 17178669
TI  - Lupus anticoagulant and anticardiolipin antibodies in polytransfused beta
      thalassemia major.
AB  - The currently used therapeutic strategies in beta thalassemia have prolonged the
      survival for many patients; this longer survival has been accompanied by the
      development of a number of unexpected complications, these include hemostatic
      derangements. The presence of anti-phospholipid antibodies (APA) (lupus
      anticoagulant, LA and anti-cardiolipid antibody, ACA) has recently been reported
      in polytransfused patients of beta thalassemia. In this study 50 patients with
      beta thalassemia major (beta-TM) who had received at least 20 transfusions were
      evaluated for presence of antiphospholipid antibodies and correlated with a
      number of clinical and hemostatic parameters. About 32% cases had developed a
      minor bleeding tendency and one also showed ecchymotic patch. None of the
      patients had thromboembolic episodes. LA was seen in 16% of cases. The mean age
      and number of transfusions were higher in LA positive patients as compared to LA
      negative patients however the results were not statistically significant. IgM ACA
      were detected in 6% of patients but no statistically significant correlation was
      found with age, number of transfusions, platelet count and coagulation
      parameters. IgG ACA were detected in 30% of cases and showed a significant
      correlation with number of blood transfusions (p = 0.016) and age (p = 0.031).
      Anti HCV antibodies were detected in 30% of patients out of which 1 had IgM ACA
      and 10 had IgG ACA. The latter showed a significant correlation with HCV
      infection. An increased incidence of LA and IgG ACA is found in polytransfused
      patients with beta-TM when compared to the normal healthy population but their
      clinical significance is yet not clearly understood.

PMID- 17178670
TI  - Effects of hydroxyurea and L-arginine on the production of nitric oxide
      metabolites in cultures of normal and sickle erythrocytes.
AB  - Previous in vitro studies suggest that erythrocytes may be a source of nitric
      oxide (NO) produced by nitric oxide synthase (NOS) or by oxyhemoglobin-mediated
      oxidation of hydroxyurea (HU). This study was performed to determine the roles of
      HU and NOS in the production of NO by normal and sickle erythrocytes. Red blood
      cells (RBCs) from normal adult hemoglobin (HbAA) and homozygous sickle cell
      subjects (HbSS) were incubated with PBS containing 0.2 mM hydrogen peroxide
      (control) for 2 h at 37 degrees C in the presence and absence of l-arginine, the
      substrate for NOS, and with l-arginine plus HU in the presence and absence of l
      NMMA, a specific inhibitor of NOS. The nitrate and nitrite metabolites of NO,
      expressed as [NOx], were measured. [NOx] in the HbAA and HbSS RBC cultures was
      not significantly different in the presence and absence of 1.0 mM l-arginine
      (p>0.1). [NOx] in the HbAA and HbSS cultures treated with a clinically relevant
      dose of HU (1.0 mM) plus 1.0 mM l-arginine was significantly greater than that in
      controls incubated with PBS and with l-arginine p < 0.01. However, [NOx] in the
      HbAA and HbSS cultures treated with 50 microg/ml l-NMMA was not significantly
      different than that in the cultures treated with HU plus l-arginine in the
      absence of l-NMMA. These findings suggest that NOx production by erythrocytes may
      be increased by treatment with HU and may not be decreased by inhibiting NOS.
      Therefore, we conclude that a therapeutic dose of HU may increase the plasma
      concentration of NO by a mechanism that does not require erythrocytes NOS
      activity.

PMID- 17178671
TI  - Application of flow cytometry in detection of red-cell-bound IgG in Coombs
      negative AIHA.
AB  - Coombs negative autoimmune hemolytic anemia (AIHA) is characterized by laboratory
      evidence of in vivo hemolysis along with a negative direct antiglobulin test
      (DAT) performed by conventional tube technique (CTT) in clinically suspected AIHA
      patients. The sensitive gel test (GT) and flow cytometry (FC) can effectively
      diagnose such patients where CTT does not detect low level of red cell
      autoantibodies. We investigated the use of FC in the serological evaluation of
      CTT DAT negative AIHA and its comparison with GT DAT. Of the 50 patients with
      suspected AIHA, CTT DAT was negative in 5 patients (Coombs negative AIHA). GT DAT
      could detect red cell autoantibodies in 4 of these 5 patients. Monospecific GT
      DAT showed IgG and/or C3d as the responsible autoantibody. FC was considered as
      reactive when MFI was >3.6 (mean of 20 healthy negative volunteers +2SD). FC was
      reactive in all five Coombs negative AIHA patients. The mean MFI in five known
      CTT DAT positive samples taken for comparison was significantly higher compared
      to 5 DAT negative AIHA (18.3 +/- 7.78 vs. 7.88 +/- 1.35, p < 0.05). There was
      poor correlation between strength of GT DAT and MFI by FC. We conclude that FC is
      more sensitive test than the CTT and helps in the serological diagnosis of Coombs
      negative AIHA. However, in resource poor settings, GT DAT can be a good
      alternative to FC.

PMID- 17178672
TI  - Extracellular accumulation of bioactive substances; interleukin-1beta (IL-1beta)
      and plasminogen activator inhibitor-1 (PAI-1) in stored blood units and relation
      to bacterial contamination.
AB  - Bacterial contamination of blood and its cellular components remains an
      unresolved problem in transfusion medicine and is considered to be the most
      common microbiological cause of transfusion associated morbidity and mortality.
      The present work was designed to explore the levels of two bioactive compounds
      interleukin-1 beta (IL-1beta) and plasminogen activator inhibitor-1 (PAI-1) in
      stored blood units and their relation to bacterial contamination of these units.
      This study was conducted on 112 blood units obtained from blood bank of Mansoura
      University Children Hospital. Sequential blood samples were obtained both
      immediately at donation and after 10 days for measurement of IL-1beta and PAI-1
      and for bacterial culture by BACTEC 9050 system. There was statistically
      significant increase in both IL-1 beta and PAI-1 (P = 0.0001) after 10 days of
      blood units storage. Bacteriological culture revealed no growth in 68% and
      positive growth in 32% of blood units. The commonest isolated organism was
      Staphylococcus aureus (15%) followed by Staphylococcus epidermedis (13%) then
      Yersinia sp. and Enterobacter sp. (2%) for each. From the present study we could
      conclude that stored blood units contain platelets and WBCs derived bioactive
      substances PAI-1 and IL-1beta which increase with the duration of blood storage.
      Furthermore, the extended duration of storage carries the danger of blood
      contamination by bacteria. Automated blood culture system seems to be helpful in
      identification of bacterial contamination of blood units. We recommend fresh
      blood transfusion as early as possible and the practice of Leucofiltration to
      avoid blood transfusion complications.

PMID- 17178675
TI  - MR in patients with pacemakers and ICDs: Defining the issues.
AB  - There has been great controversy related to performance of magnetic resonance
      imaging in patients with pacemakers and implantable cardiac defibrillators.
      Recent questions have been raised regarding whether contraindications are
      absolute or relative. Although there are theoretical as well as documented issues
      relating to device malfunction, data suggest that scanning patients with devices
      may be feasible when important clinical questions need to be addressed by
      following strict guidelines. Advanced knowledge and understanding of
      electrophysiologic as well as magnetic resonance imaging-related issues, and a
      multidisciplinary, collaborative approach is required to further define the role
      of MR in patients with pacemakers and implantable cardiac defibrillators.

PMID- 17178674
TI  - Guidelines for training in Cardiovascular Magnetic Resonance (CMR).
AB  - These "Guidelines for Training in Cardiovascular Magnetic Resonance" were
      developed by the Clinical Practice Committee of the Society for Cardiovascular
      Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

PMID- 17178676
TI  - Cardiovascular magnetic resonance at 0.5T in five patients with permanent
      pacemakers.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) yields important clinical
      information which often cannot be obtained from other imaging modalities. Cardiac
      pacemakers have conventionally been considered a contraindication to CMR, and
      relatively few data exist on CMR in such patients. METHODS AND RESULTS: We
      present 5 patients who underwent 6 CMR scans in a 0.5 Tesla scanner. The patients
      were non-pacemaker dependent, and the pacemakers were reprogrammed prior to
      scanning to have sub-threshold output. Spin echo, gradient echo and real-time
      sequences were used with specific absorption rates of up to 0.1 W/kg. A
      cardiologist was present during each scan, and the patient had continuous
      electrocardiographic and non-invasive monitoring of vital signs. Five of the
      scans were carried out without incident providing useful diagnostic information,
      which was not compromised by obvious artifact from the pacemaker box. In one
      case, the pacemaker began pacing at maximum voltage at a fixed rate of 100. This
      patient was removed from the magnet, and there were no clinical sequelae. The
      mean pre-and post-scan ventricular lead voltage threshold was the same (2.28 V vs
      2.28 V). CONCLUSION: Our experience is that CMR at 0.5T in non-pacemaker
      dependent patents can be performed in closely supervised circumstances where the
      benefit-risk assessment is considered positive.

PMID- 17178677
TI  - Cardiac pacemakers and implantable cardioverter defibrillators: in vitro magnetic
      resonance imaging evaluation at 1.5-tesla.
AB  - RATIONALE AND OBJECTIVES: To evaluate the effect of Magnetic Resonance Imaging
      (MRI) performed at 1.5-Tesla on current generation pacemakers and ICDs to
      identify safe parameters for MRI examinations. METHODS: Pacemakers (Identity ADx
      XL DR+ 5386 and Identity ADx DR + 5380 generators; 1688T/52-cm atrial and
      ventricular leads) and ICDs (Atlas + V-243, Epic + V-236, and Epic + HF V-350
      generators; Riata 1581/65-cm and QuickSite 1056K/75-cm leads; St. Jude Medical,
      Sylmar, California, USA) were evaluated for magnetic field interactions. MRI
      related heating was assessed using various levels of RF power (SARs) and
      conditions that included scans on different body regions. Functional aspects of
      the devices were evaluated immediately before and after MRI procedures utilizing
      nine different pulse sequences. Induced currents were measured using a custom
      built system. RESULTS: Magnetic field interactions will not create a hazard for
      these pacemakers and ICDs. All scans of the "head" and "lumbar" regions resulted
      in temperature changes < or =0.5 degrees C at SARs ranging from 2.0 to 3.0-W/kg.
      For the "chest" area, temperature increases ranged from 0.4 degrees C to 3.6
      degrees C at an SAR of 2.0-W/kg. No memory corruption, hardware changes, or
      changes in device parameters were seen. Magnetic field gradients have a low
      likelihood of inducing currents that would stimulate the heart. CONCLUSIONS: No
      hazardous magnetic field interactions or physiologically significant heating
      occurred for certain conditions. There was no permanent effect on device
      function. By following specific conditions, these pacemakers and ICDs may be safe
      for patients scanned at 1.5-Tesla.

PMID- 17178678
TI  - Diffusion-prepared segmented steady-state free precession: Application to 3D
      black-blood cardiovascular magnetic resonance of the thoracic aorta and carotid
      artery walls.
AB  - This work developed a three-dimensional (3D) diffusion-prepared segmented steady
      steady free precession (DP-SSFP) cardiovascular magnetic resonance (CMR) sequence
      for black-blood (BB) thoracic aortic and carotid wall visualization. In 14
      healthy volunteers, BB CMR of the thoracic aorta (n = 7) and carotid arteries (n
      = 7) was performed over 12 cm and 3 cm of transversal coverage, respectively,
      with a single 3D DP-SSFP acquisition and multiple two-dimensional (2D) slices
      using a T2-weighted (T2W) double inversion-recovery fast spin-echo (DIR-FSE)
      sequence. Arterial wall area (WA), lumen area (LA), and wall-lumen contrast-to
      noise ratio (CNR) measured from the 3D DP-SSFP images were compared to those
      measured from the 2D T2W DIR-FSE images. Strong agreement in WA and LA between
      the two techniques was observed in the thoracic aorta (WA: intraclass correlation
      coefficient (ICC) = 0.866, LA: ICC = 0.993; p < 0.001 for both) and carotid
      arteries (WA: ICC = 0.939, LA: ICC = 0.991; p < 0.001 for both). Adjusted for
      slice thickness and number of slices, higher effective CNR per unit time (i.e.,
      CNR efficiency) was attained with 3D DP-SSFP than 2D T2W DIR-FSE during thoracic
      aortic wall imaging (11.6 +/- 1.4 vs. 2.9 +/- 0.5; p < 0.001) and carotid artery
      wall imaging (10.1 +/- 1.9 vs. 3.1 +/- 0.5; p < 0.001). Diffusion-prepared
      segmented SSFP is a promising vessel wall CMR sequence that allows for 3D
      acquisition of thin and contiguous slices with BB image contrast.

PMID- 17178679
TI  - Aortic pathophysiology by cardiovascular magnetic resonance in patients with
      clinical suspicion of coronary artery disease.
AB  - PURPOSE: To correlate cardiovascular magnetic resonance (CMR)-based measurement
      of aortic pulse wave velocity (PWV) with serum markers for atherosclerosis and
      plaque burden in the thoracic aorta. METHOD: Individuals with risk factors for
      coronary atherosclerosis underwent CMR pulse wave velocity examination of the
      descending thoracic aorta and computed tomography for coronary calcium scoring.
      Inversion recovery images allowed quantification of aortic plaque. Serum lipids
      and c-reactive protein levels were measured. RESULTS: Mean PWV did not correlate
      with presence of aortic plaque (p = 0.55). Subgroup analysis showed no
      significant correlation with PWV and total plaque. PWV and pulse pressure
      correlated (PP) (R2 0.38, p = 0.0003), but PWV and other predictor variables did
      not. Total plaque area correlated with aortic diameter (p = 0.0066). CONCLUSIONS:
      In patients with suspected coronary artery disease, aortic pulse wave velocity
      reflects increased aortic stiffness demonstrated by elevated pulse pressure, but
      does not directly correlate with aortic plaque or serum markers for arterial
      disease.

PMID- 17178680
TI  - Reproducibility of free-breathing cardiovascular magnetic resonance coronary
      angiography.
AB  - OBJECTIVE: Contemporary free-breathing non contrast enhanced cardiovascular
      magnetic resonance angiography (CMRA) was qualitatively and quantitatively
      evaluated to ascertain the reproducibility of the method for coronary artery
      luminal dimension measurements. SUBJECTS AND METHODS: Twenty-two healthy
      volunteers (mean age 32 +/- 7 years, 12 males) without coronary artery disease
      were imaged at 2 centers (1 each in Europe and North America) using navigator
      gated and corrected SSFP CMRA on a commercial whole body 1.5T System. Repeat
      images of right (RCA, n = 21), left anterior descending (LAD, n = 14) and left
      circumflex (LCX, n = 14) coronary arteries were obtained in separate sessions
      using identical scan protocol and imaging parameters. True visible vessel length,
      signal-to-noise (SNR), contrast-to-noise ratios (CNR) and the average luminal
      diameter over the first 4 cm of the vessel were measured. Intra-observer, inter
      observer and inter-scan reproducibility of coronary artery luminal diameter were
      determined using Pearson's correlation, Bland-Altman analysis and intraclass
      correlation coefficients (ICC). RESULTS: CNR, SNR and the mean length of the RCA,
      LAD and LCX imaged for original and repeat scans were not significantly different
      (all p > 0.30). There was a high degree of intra-observer, inter-observer and
      inter-scan agreements for RCA, LAD and LCX luminal diameter respectively on Bland
      Altman and ICC analysis (ICC's for RCA: 0.98. 0.98 and 0.86; LAD: 0.89, 0.89 and
      0.63; LCX: 0.95, 0.94 and 0.79). CONCLUSION: In a 2-center study, we demonstrate
      that free-breathing 3D SSFP CMRA can visualize long continuous segments of
      coronary vessels with highly reproducible measurements of luminal diameter.

PMID- 17178681
TI  - Anomalous right coronary artery from the pulmonary artery: noninvasive diagnosis
      and serial evaluation.
AB  - Isolated anomalous origin of the right coronary artery from the main pulmonary
      artery (ARCAPA) is a rare congenital cardiac malformation. We reviewed the
      current literature and found only 31 patients with ARCAPA. We report the first
      case that was diagnosed and followed on a noninvasive basis with cardiovascular
      magnetic resonance after surgical re-implantation. This report of a patient with
      ARCAPA showed resolving coronary artery sizes secondary to decreased pulmonary
      steal. Cardiovascular magnetic resonance is an accurate and reliable imaging
      modality that allows serial noninvasive follow up in patients with coronary
      artery anomalies.

PMID- 17178682
TI  - Comparison of gadolinium-enhanced cardiovascular magnetic resonance angiography
      with high-resolution black blood cardiovascular magnetic resonance for assessing
      carotid artery stenosis.
AB  - PURPOSE: Carotid angiography is used to assess stroke risk, but it cannot
      reliably characterize plaque burden because the vessel remodels during plaque
      formation. High-resolution black blood cardiovascular magnetic resonance (BBCMR)
      depicts the outer wall thereby providing a truer estimate of plaque size. We
      compared carotid stenosis by gadolinium enhancement cardiovascular magnetic
      resonance angiography (CMRA) versus high-resolution BBCMR. METHODS: Twenty-four
      subjects (M:F = 20:4; ages 57-83 years) with carotid atherosclerosis underwent
      CMRA and transaxial BBCMR through the stenosis. Area and diameter stenosis
      measurements by NASCET criteria using CMRA images were compared to area stenosis
      measurements based on outer wall and lumen contours drawn on corresponding BBCMR
      images. RESULTS: Area stenosis by CMRA correlated with area stenosis by BBCMR (r
      = 0.77; 95% CI: 0.58, 0.89). BBCMR values exceeded corresponding CMRA area
      measurements in 20 of 24 cases, with the remainder being highly stenotic (> 90%).
      CONCLUSION: CMRA yields lower estimates of luminal narrowing compared to BBCMR,
      which delineates the outer wall and accounts for vascular remodeling. BBCMR could
      serve as a new measure of narrowing to guide management, but prospective studies
      are needed to better understand the clinical implications of this new scale of
      disease.

PMID- 17178683
TI  - Reproducibility and reliability of atherosclerotic plaque volume measurements in
      peripheral arterial disease with cardiovascular magnetic resonance.
AB  - A high resolution, noninvasive approach to quantify atherosclerotic plaque in the
      peripheral vasculature could have significant clinical and research utility.
      Seventeen patients with peripheral arterial disease (PAD) were studied in a 1.5T
      CMR scanner. Atherosclerotic plaque volume in the superficial femoral artery was
      measured and interobserver, intraobserver, and test-retest variability
      determined. Nineteen vessels were studied with mean acquisition time of 13.1
      minutes per vessel. Mean plaque volume was 7.27 +/- 3.73 cm3. Intra-observer
      intraclass correlation was R = 0.997, inter-observer was R = 0.987, and test
      retest reproducibility was R = 0.996. Thus, high resolution measurement of plaque
      volume in PAD is reliable and reproducible.

PMID- 17178684
TI  - Ultrafast time-resolved contrast-enhanced 3D pulmonary venous cardiovascular
      magnetic resonance angiography using SENSE combined with CENTRA-keyhole.
AB  - PURPOSE: To evaluate the diagnostic benefit of time-resolved CENTRA-keyhole
      contrast-enhanced cardiovascular magnetic resonance angiography (CE-CMRA) for
      improving arterial-venous separation of pulmonary vessels. METHODS: Twenty-three
      patients (18 males; age = 58 +/- 11y) after radiofrequency pulmonary vein
      isolation to treat atrial fibrillation were examined using CENTRA-keyhole based
      multi-phase 3D CE-CMRA yielding 6 near-isotropic 3D datasets every 1.6 s (50-60
      coronal partitions, 1.4 x 1.4 x 1.3 mm, SENSE-factor 3). Results were compared
      with conventional non-keyhole CE-CMRA (identical parameters, SENSE-factor 2).
      RESULTS: Data acquisition was accelerated by a speedup factor of approximately 9
      compared with the reference CE-CMRA (SENSE 1.5*, keyhole 6*). No pulmonary venous
      stenoses were detected by either method, overall pulmonary venous diameters were
      17.1 +/- 3.6 mm. Applying Bland-Altman analysis, vessel diameters differed by a
      mean of 0.1 mm + 2.1 mm/-2.0 mm (mean +/- 2 SD), indicating close agreement
      between both techniques. Interobserver variability was higher for CENTRA-keyhole
      (mean = 0.1 mm; mean +/- 2 SD: +2.5 mm/-2.3 mm) compared to conventional
      technique (0.0 mm; +1.6 mm/-1.5 mm), corresponding to a percentual deviation
      (mean +/- 2 SD) of the mean diameter of approximately +/- 15% (keyhole CE-CMRA)
      and +/- 10% (conventional CE-CMRA), respectively. Using keyhole-based time
      resolved CE-CMRA, the contrast between pulmonary veins versus aorta/pulmonary
      artery was significantly increased (p < 0.05), which improved vessel depiction.
      In 12 cases, the contrast bolus arrival was delayed in one of the pulmonary veins
      by 1 dynamic frame (= 1.6 seconds); in 7 cases by 2 frames (= 3.2 seconds) and in
      1 subject by 3 frames (= 4.8 seconds). The bolus usually appeared first in the
      upper right pulmonary vein whereas a delay occurred most often in the lower left
      pulmonary vein. CONCLUSIONS: Conventional CE-CMRA may be advantageous for
      accurate vessel size measures as evidenced by superior interobserver
      reproducibility in this study. Multi-dynamic CE-CMRA using CENTRA-keyhole with
      SENSE, however, allows for improved arterio-venous separation of pulmonary
      vessels and additional dynamical information on pulmonary venous perfusion, while
      maintaining high spatial resolution. Exact bolus timing is no longer needed.

PMID- 17178685
TI  - Modern imaging technologies in toxicologic pathology: An overview.
AB  - Modern imaging technology, now utilized in most biomedical research areas
      (bioimaging), enables the detection and visualization of biological processes at
      various levels of the molecule, organelle, cell, tissue, organ and/or whole body.
      In toxicologic pathology, the impact of modern imaging technology is becoming
      apparent from digital histopathology to novel molecular imaging for in vivo
      studies. This overview summarizes recent progresses in digital microscopy imaging
      and newly developed digital slide techniques. Applications of virtual microscopy
      imaging are discussed and compared to traditional optical microscopy reading. New
      generation digital pathology approaches, including automatic slide inspection,
      digital slide databases and image management are briefly introduced. Commonly
      used in vivo preclinical imaging technologies are also summarized. While most of
      these new imaging techniques are still undergoing rapid development, it is
      important that toxicologic pathologists embrace and utilize these technologies as
      advances occur.

PMID- 17178686
TI  - Nasal cytotoxic and carcinogenic activities of systemically distributed organic
      chemicals.
AB  - Toxicity and carcinogenicity in the mucosa of the nasal passages in rodents has
      been produced by a variety of organic chemicals which are systemically
      distributed. In this review, 14 such chemicals or classes were identified that
      produced rodent nasal cytotoxicity, but not carcinogenicity, and 11 were
      identified that produced nasal carcinogenicity. Most chemicals that affect the
      nasal mucosa were either concentrated in that tissue or readily activated there,
      or both. All chemicals with effects in the nasal mucosa that were DNA-reactive,
      were also carcinogenic, if adequately tested. None of the rodent nasal cytotoxins
      has been identified as a human systemic nasal toxin. This may reflect the lesser
      biotransformation activity of human nasal mucosa compared to rodent and the much
      lower levels of human exposures. None of the rodent carcinogens lacking DNA
      reactivity has been identified as a nasal carcinogen or other cancer hazard to
      humans. Some DNA-reactive rodent carcinogens that affect the nasal mucosa, as
      well as other tissues, have been associated with cancer at various sites in
      humans, but not the nasal cavity. Thus, findings in only the rodent nasal mucosa
      do not necessarily predict either a toxic or carcinogenic hazard to that tissue
      in humans.

PMID- 17178687
TI  - Toxicity profiles in mice treated with hepatotumorigenic and non
      hepatotumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and
      myclobutanil.
AB  - Conazoles comprise a class of fungicides used in agriculture and as
      pharmaceutical products. The fungicidal properties of conazoles are due to their
      inhibition of ergosterol biosynthesis. Certain conazoles are tumorigenic in
      rodents; both propiconazole and triadimefon are hepatotoxic and hepatotumorigenic
      in mice, while myclobutanil is not a mouse liver tumorigen. As a component of a
      large-scale study aimed at determining the mode(s) of action for tumorigenic
      conazoles, we report the results from comparative evaluations of liver and body
      weights, liver histopathology, cell proliferation, cytochrome P450 (CYP)
      activity, and serum cholesterol, high-density lipoprotein and triglyceride levels
      after exposure to propiconazole, triadimefon, and myclobutanil. Male CD-1 mice
      were treated in the feed for 4, 30, or 90 days with triadimefon (0, 100, 500, or
      1800 ppm), propiconazole (0, 100, 500, or 2500 ppm) or myclobutanil (0, 100, 500,
      or 2000 ppm). Alkoxyresorufin O-dealkylation (AROD) assays indicated that all 3
      chemicals induced similar patterns of dose-related increases in metabolizing
      enzyme activity. PROD activities exceeded those of MROD, and EROD with
      propiconazole inducing the highest activities of PROD. Mice had similar patterns
      of dose-dependent increases in hepatocyte hypertrophy after exposure to the 3
      conazoles. High-dose exposures to propiconazole and myclobutanil, but not
      triadimefon, were associated with early (4 days) increases in cell proliferation.
      All the chemicals at high doses reduced serum cholesterol and high-density
      lipoprotein (HDL) levels at 30 days of treatment, while only triadimefon had this
      effect at 4 days of treatment and only myclobutanil and propiconazole at 90 days
      of treatment. Overall, the tumorigenic and nontumorigenic conazoles induced
      similar effects on mouse liver CYP enzyme activities and pathology. There was no
      specific pattern of tissue responses that could consistently be used to
      differentiate the tumorigenic conazoles, propiconazole, and triadimefon, from the
      nontumorigenic myclobutanil. These findings serve to anchor other transcriptional
      profiling studies aimed at probing differences in key events and modes of action
      for tumorigenic and nontumorigenic conazoles.

PMID- 17178688
TI  - Transcriptional profiles in liver from mice treated with hepatotumorigenic and
      nonhepatotumorigenic triazole conazole fungicides: Propiconazole, triadimefon,
      and myclobutanil.
AB  - Conazoles are environmental and pharmaceutical fungicides. The present study
      relates the toxicological effects of conazoles to alterations of gene and pathway
      transcription and identifies potential modes of tumorigenic action. In a
      companion study employing conventional toxicological bioassays (Allen et al.,
      2006), male CD-1 mice were fed triadimefon, propiconazole, or myclobutanil in a
      continuous oral-dose regimen for 4, 30, or 90 days. These conazoles were found to
      induce hepatomegaly, to induce high levels of hepatic pentoxyresorufin-O
      dealkylase activity, to increase hepatic cell proliferation, to decrease serum
      cholesterol, and to increase serum triglycerides. Differentially expressed genes
      and pathways were identified using Affymetrix GeneChips. Gene-pathway
      associations were obtained from the Kyoto Encyclopedia of Genes and Genomes,
      Biocarta, and MetaCore compendia. The pathway profiles of each conazole were
      different at each time point. In general, the number of altered metabolism,
      signaling, and growth pathways increased with time and dose and were greatest
      with propiconazole. All conazoles had effects on nuclear receptors as evidenced
      by increased expression and enzymatic activities of a series of related
      cytochrome P450s (CYP). A subset of altered genes and pathways distinguished the
      three conazoles from each other. Triadimefon and propiconazole both altered
      apoptosis, cell cycle, adherens junction, calcium signaling, and EGFR signaling
      pathways. Triadimefon produced greater changes in cholesterol biosynthesis and
      retinoic acid metabolism genes and in selected signaling pathways. Propiconazole
      had greater effects on genes responding to oxidative stress and on the
      IGF/P13K/AKt/PTEN/mTor and Wnt-beta-catenin pathways. In conclusion, while
      triadimefon, propiconazole, and myclobutanil had similar effects in mouse liver
      on hepatomegaly, histology, CYP activities, cell proliferation, and serum
      cholesterol, genomic analyses revealed major differences in their gene expression
      profiles.

PMID- 17178689
TI  - Transcriptional profiles in liver from rats treated with tumorigenic and non
      tumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and
      myclobutanil.
AB  - Conazoles are a class of fungicides used as pharmaceutical and agricultural
      agents. In chronic bioassays in rats, triadimefon was hepatotoxic and induced
      follicular cell adenomas in the thyroid gland, whereas, propiconazole and
      myclobutanil were hepatotoxic but had no effect on the thyroid gland. These
      conazoles administered in the feed to male Wistar/Han rats were found to induce
      hepatomegaly, induce high levels of pentoxyresorufin-O-dealkylase, increase cell
      proliferation in the liver, increase serum cholesterol, decrease serum T3 and T4,
      and increase hepatic uridine diphosphoglucuronosyl transferase activity. The goal
      of the present study was to define pathways that explain the biologic outcomes.
      Male Wistar/Han rats (3 per group), were exposed to the 3 conazoles in the feed
      for 4, 30, or 90 days of treatment at tumorigenic and nontumorigenic doses.
      Hepatic gene expression was determined using high-density Affymetrix GeneChips
      (Rat 230_2). Differential gene expression was assessed at the probe level using
      Robust Multichip Average analysis. Principal component analysis by treatment and
      time showed within group sample similarity and that the treatment groups were
      distinct from each other. The number of altered genes varied by treatment, dose,
      and time. The greatest number of altered genes was induced by triadimefon and
      propiconazole after 90 days of treatment, while myclobutanil had minimal effects
      at that time point. Pathway level analyses revealed that after 90 days of
      treatment the most significant numbers of altered pathways were related to cell
      signaling, growth, and metabolism. Pathway level analysis for triadimefon and
      propiconazole resulted in 71 altered pathways common to both chemicals. These
      pathways controlled cholesterol metabolism, activation of nuclear receptors, and
      N-ras and K-ras signaling. There were 37 pathways uniquely changed by
      propiconazole, and triadimefon uniquely altered 34 pathways. Pathway level
      analysis of altered gene expression resulted in a more complete description of
      the associated toxicological effects that can distinguish triadimefon from
      propiconazole and myclobutanil.

PMID- 17178690
TI  - Toxicity profiles in rats treated with tumorigenic and nontumorigenic triazole
      conazole fungicides: Propiconazole, triadimefon, and myclobutanil.
AB  - Conazoles are a class of azole based fungicides used in agriculture and as
      pharmaceutical products. They have a common mode of antifungal action through
      inhibition of ergosterol biosynthesis. Some members of this class have been shown
      to be hepatotoxic and will induce mouse hepatocellular tumors and/or rat thyroid
      follicular cell tumors. The particular mode of toxic and tumorigenic action for
      these compounds is not known, however it has been proposed that triadimefon
      induced rat thyroid tumors arise through the specific mechanism of increased TSH.
      The present study was designed to identify commonalities of effects across the
      different conazoles and to determine unique features of the tissue responses that
      suggest a toxicity pathway and a mode of action for the observed thyroid response
      for triadimefon. Male Wistar/Han rats were treated with triadimefon (100, 500,
      1800 ppm), propiconazole (100, 500, 2500 ppm), or myclobutanil (100, 500, 2000
      ppm) in feed for 4, 30, or 90 days. The rats were evaluated for clinical signs,
      body and liver weight, histopathology of thyroid and liver, hepatic metabolizing
      enzyme activity, and serum T3, T4, TSH, and cholesterol levels. There was a dose
      dependent increase in liver weight but not body weight for all treatments. The
      indication of cytochrome induction, pentoxyresorufin O-dealkylation (PROD)
      activity, had a dose-related increase at all time points for all conazoles.
      Uridine diphopho-glucuronosyl transferase (UDPGT), the T4 metabolizing enzyme
      measured as glucuronidation of 1-naphthol, was induced to the same extent after
      30 and 90 days for all three conazoles. Livers from all high dose treated rats
      had centrilobular hepatocyte hypertrophy after 4 days, while only triadimefon and
      propiconazole treated rats had hepatocyte hypertrophy after 30 days, and only
      triadimefon treated rats had hepatocyte hypertrophy after 90 days. Thyroid
      follicular cell hypertrophy, increased follicular cell proliferation, and colloid
      depletion were present only after 30 days in rats treated with the high dose of
      triadimefon. A dose-dependent decrease in T4 was present after 4 days with all 3
      compounds but only the high doses of propiconazole and triadimefon produced
      decreased T4 after 30 days. T3 was decreased after high-dose triadimefon after 4
      days and in a dose-dependent manner for all compounds after 30 days. Thyroid
      hormone levels did not differ from control values after 90 days and TSH was not
      increased in any exposure group. A unique pattern of toxic responses was not
      identified for each conazole and the hypothesized mode of action for triadimefon
      induced thyroid gland tumors was not supported by the data.

PMID- 17178691
TI  - Urothelial carcinogenesis in the urinary bladder of male rats treated with
      muraglitazar, a PPAR alpha/gamma agonist: Evidence for urolithiasis as the
      inciting event in the mode of action.
AB  - Muraglitazar, a PPARalpha/gamma agonist, dose-dependently increased urinary
      bladder tumors in male Harlan Sprague-Dawley (HSD) rats administered 5, 30, or 50
      mg/kg/day for up to 2 years. To determine the mode of tumor development, male HSD
      rats were treated daily for up to 21 months at doses of 0, 1, or 50 mg/kg while
      being fed either a normal or 1% NH4Cl-acidified diet. Muraglitazar-associated,
      time-dependent changes in urine composition, urothelial mitogenesis and
      apoptosis, and urothelial morphology were assessed. In control and treated rats
      fed a normal diet, urine pH was generally > or = 6.5, which facilitates formation
      of calcium-and magnesium-containing solids, particularly in the presence of other
      prolithogenic changes in rat urine. Urinary citrate, an inhibitor of
      lithogenesis, and soluble calcium concentrations were dose dependently decreased
      in association with increased calcium phosphate precipitate, crystals and/or
      microcalculi; magnesium ammonium phosphate crystals and aggregates; and calcium
      oxalate-containing thin, rod-like crystals. Morphologically, sustained urothelial
      cytotoxicity and proliferation with a ventral bladder predilection were noted in
      treated rats by month 1 and urinary carcinomas with a similar distribution
      occurred by month 9. Urothelial apoptotic rates were unaffected by muraglitazar
      treatment or diet. In muraglitazar-treated rats fed an acidified diet, urine pH
      was invariably < 6.5, which inhibited formation of calcium-and magnesium
      containing solids. Moreover, dietary acidification prevented the urothelial
      cytotoxic, proliferative, and tumorigenic responses. Collectively, these data
      support an indirect pharmacologic mode of urinary bladder tumor development
      involving alterations in urine composition that predispose to urolithiasis and
      associated decreases in urine-soluble calcium concentrations.

PMID- 17178692
TI  - Application of visualization tools to the analysis of histopathological data
      enhances biological insight and interpretation.
AB  - Gene expression profiling, metabolomic screens, and other high-dimensional
      methods have become an integral part of many biological investigations. To
      facilitate interpretation of these data, it is important to have detailed
      phenotypic data--including histopathology--to which these data can be associated,
      or anchored. However, as the amount of phenotypic data increases, associations
      within and across these data can be difficult to visualize and interpret. We have
      developed an approach for categorizing and clustering biologically related
      histopathological diagnoses to facilitate their visualization, thereby increasing
      the possibility of identifying associations and facilitating the comparison with
      other data streams. In this study, we utilize histopathological data generated as
      part of a standardized toxicogenomics compendium study to generate composite
      histopathological scores and to develop visualizations that facilitate biological
      insight. The validity of this approach is illustrated by the identification of
      transcripts that correlate with the pathology diagnoses that comprise the
      categories of "response to hepatocellular injury" and "repair." This approach is
      broadly applicable to studies in which histopathology is used to phenotypically
      anchor other data, and results in visualizations that facilitate biological
      interpretation and the identification of associations and relationships within
      the data.

PMID- 17178693
TI  - Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in
      a 2-year study in Fischer 344 rats.
AB  - The carcinogenic potential of human parathyroid hormone 1-84 (PTH) was assessed
      by daily subcutaneous injection (0, 10, 50, 150 microg/kg/day) for 2 years in
      Fischer 344 rats. Histopathological analyses were conducted on the standard set
      of soft tissues, tissues with macroscopic abnormalities, selected bones, and
      bones with abnormalities identified radiographically. All PTH doses caused
      widespread osteosclerosis and significant, dose-dependent increases in femoral
      and vertebral bone mineral content and density. In the mid-and high-dose groups,
      proliferative changes in bone increased with dose. Osteosarcoma was the most
      common change, followed by focal osteoblast hyperplasia, osteoblastoma, osteoma
      and skeletal fibrosarcoma. The incidence of bone neoplasms was comparable in
      control and low-dose groups providing a noncarcinogenic dose for PTH of 10
      microg/kg/day at a systemic exposure to PTH that is 4.6-fold higher than for a
      100 microg dose in humans. The ability of PTH to interact with and balance the
      effects of both the PTH-1 receptor and the putative C-terminal PTH receptor, may
      lead to the lower carcinogenic potential observed with PTH than reported
      previously for teriparatide.

PMID- 17178694
TI  - Histological investigation of diagnostically challenging tubule profiles in
      advanced chronic progressive nephropathy (CPN) in the fischer 344 RaT.
AB  - Recently, guidelines were suggested for discriminating proliferative-appearing
      tubule profiles encountered in advanced spontaneous chronic progressive
      nephropathy (CPN) of rats, from hyperplastic precursors of renal tubule tumors
      (Hard and Seely, 2005). These recommendations were based on histological
      evaluation of a large number of cases of severe to end-stage CPN in male F344
      rats from 8 separate 2-year carcinogenicity studies held in the Archives of the
      National Toxicology Program, NIEHS. This work has now been extended to
      characterize the various lesions further, mainly by serial sectioning to track
      their origin and fate within the adjacent renal tissue, but also by applying
      special staining procedures such as immunohistochemical assessment of
      proliferative activity, as well as fluorescence microscopy, to seek further
      differences from atypical tubule hyperplasia. The results obtained from these
      additional investigations support the contention that certain tubule profiles
      with a misleading proliferative appearance, sometimes found in advanced CPN,
      should be distinguished from preneoplastic tubule foci, and regarded as
      components of the nephropathy process.

PMID- 17178695
TI  - Translocation pathway of the intratracheally instilled ultrafine particles from
      the lung into the blood circulation in the mouse.
AB  - Recently, it has been demonstrated that ultrafine particles (UFPs) are able to
      translocate from the lung into the systemic circulation. Precise mechanisms of
      the anatomical translocation (crossing the air-blood barrier) of inhaled UFPs at
      the alveolar wall are not fully understood. In this study, we examined the
      translocation pathway of the intratracheally instilled ultrafine carbon black
      (UFCB) from the lung into the blood circulation in mouse. Electron microscopy
      demonstrated accumulation of intratracheally instilled UFCB in the large-sized
      gaps developing between the cytoplasmic processes of the alveolar epithelial
      cells, possibly as a result of shrinkage of cytoplasm, by receiving
      stimulus/signals generated and released following UFCB attachment on the alveolar
      epithelial cells. Occasional penetration of the accumulated UFCB into the
      alveolar basement membrane, exposing to the air space, was observed at the gap.
      These results suggest that inhaled UFPs may, in part, pass the air-blood barrier
      through the large-sized gap formed between the alveolar epithelial cells.

PMID- 17178696
TI  - Acute and subacute pulmonary toxicity of low dose of ultrafine colloidal silica
      particles in mice after intratracheal instillation.
AB  - To study the acute and subacute lung toxicity of low dose of ultrafine colloidal
      silica particles (UFCSs), mice were intratracheally instilled with 0, 0.3, 3, 10,
      30 or 100 microg of UFCSs. Cellular and biochemical parameters in bronchoalveolar
      lavage fluid (BALF), histological alteration and the body weight were determined
      at 3 days after instillation. Exposure to 30 or 100 microg of UFCSs produced
      moderate to severe pulmonary inflammation and tissue injury. To investigate the
      time response, mice were instilled with 30 microg of UFCSs and sacrificed at
      intervals from 1 to 30 days post-exposure. UFCSs induced moderate pulmonary
      inflammation and injury on BALF indices at acute period; however, these changes
      gradually regressed until recovery during the experiment. Concomitant
      histopathological and laminin immunohistochemical findings generally correlated
      to BALF data. TUNEL analyses in UFCSs-treated animals showed a significant
      increase of the apoptotic index in lung parenchyma at all observation times. 8
      OHdG expression occurred in lung epithelial cells and activated macrophages,
      which correlated to lung lesions in UFCSs-treated mice. These findings suggest
      that instillation of a small dose of UFCSs causes transient acute moderate lung
      inflammation and tissue damage. Oxidative stress and apoptosis may underlie the
      lung tissue injury induction.

PMID- 17178697
TI  - Virtual microscopy for comparative pathology.

PMID- 17178699
TI  - The diagnosis and differential diagnosis of endogenous Cushing's syndrome.
AB  - Cushing's syndrome (CS) is a physically and psychologically disabling disease
      associated with high morbidity resulting from inappropriate elevation of
      circulating free cortisol levels. The main features of CS are disturbance of the
      normal circadian rhythm of cortisol secretion, impairment of the normal feedback
      of the hypothalamo-pituitary-adrenal (HPA)-axis, and excessive integrated 24
      hours cortisol secretion. All biochemical tests used for the diagnosis of CS rely
      upon the ascertainment of a disturbance of these features. However, the diagnosis
      of CS (endogenous hypercortisolism) still remains a challenge, although the
      evolution of several diagnostic tests has allowed diagnosis at an earlier stage.
      In the initial investigation of CS, tests of high sensitivity are required to
      identify patients at risk, which are followed by tests of high specificity to
      confirm the diagnosis and establish the precise aetiology. This review will
      discuss the various causes of endogenous CS and focus on established and evolving
      diagnostic procedures used for its diagnosis, as several studies with large
      number of patients have recently appeared in the literature validating current
      practice and proposing improved diagnostic algorithms.

PMID- 17178700
TI  - Improvement of insulin sensitivity in patients with type 2 diabetes mellitus
      after oral administration of alpha-lipoic acid.
AB  - BACKGROUND: Amelioration of insulin resistance could improve both glycaemic
      control and cardiovascular risk factors in patients with type 2 diabetes
      mellitus. Alpha-lipoic acid has been shown to improve insulin action after
      parenteral administration. OBJECTIVE: the aim of the study was to assess the
      effect of oral administration of alpha-lipoic acid on insulin sensitivity in
      patients with type 2 diabetes. DESIGN: twelve patients (mean+/-sD; age 52.9+/-9.9
      yrs; body mass index 33.9+/-7.4 kg/m(2)) were treated with oral alpha-lipoic
      acid, 600 mg twice daily over a period of 4 weeks. twelve subjects with normal
      glucose tolerance served as a control group in terms of insulin sensitivity (Is).
      Is was measured by a 2h manual hyperinsulinaemic (insulin infusion rate-40 mU/m(2
      )body surface area/min) euglycaemic (blood glucose kept at 5 mmol/l) clamp
      technique and expressed as a glucose disposal rate (M) and insulin sensitivity
      index (IsI). RESULTS: At the end of the treatment period, Is of diabetic patients
      was significantly increased: M from 3.202+/-1.898 to 5.951+/-2.705 mg/kg/min
      (mean+/-sD), p<0.01; and IsI from 4.706+/-2.666 to 7.673+/-3.559 mg/kg/min per
      mIU/l x 100 (mean+/-sD), p<0.05. the difference was not statistically significant
      between the Is of diabetic patients after alpha-lipoic acid therapy and control
      subjects. CONCLUSION: short-term oral alpha-lipoic acid treatment increases
      peripheral insulin sensitivity in patients with type 2 diabetes mellitus.

PMID- 17178701
TI  - Effect of weight loss with or without orlistat treatment on adipocytokines,
      inflammation, and oxidative markers in obese women.
AB  - OBJECTIVE: The aim of this study was to evaluate the levels of adipose tissue
      related hormones, cytokines, and antioxidative substances in obese women before
      and after intervention with diet alone or with diet plus an inhibitor of
      gastrointestinental lipase-orlistat. DESIGN: Seventy-one obese women of
      childbearing age were included in the study and were randomly assigned into two
      groups according to the type of intervention: group A1 (n=35) included women who
      received orlistat as well as a hypocaloric diet, and group A2 (n=36) included
      women who were only on hypocaloric diet. The intervention period lasted 6 months.
      Anthropometric parameters, such as Body Weight (BW), Body Mass Index (BMI), Waist
      Circumference (WC), and %Body fat (BF) were recorded. Insulin, leptin, resistin,
      interleukin-6 (IL-6), insulin like growth factor 1 (IGF-1), tumor necrosis factor
      alpha (TNFalpha), adiponectin, hsC-reactive protein (CRP), glutathione
      peroxidase, and isoprostane were determined by appropriate methodology prior to
      and following the 6-month intervention period. Insulin resistance was measured
      using the homeostasis model assessment index (HOMA-IR). All participants had
      normal glucose tolerance. RESULTS: In both groups B MI values were lower after
      intervention and all measured parameters were ameliorated. A statistically
      significant difference was found between group A1 (orlistat plus diet) and group
      A2 (diet only) with regard to the levels of triglycerides, CRP, TNF-alpha, IGF-1,
      and isoprostane, even after correcting for weight loss. CONCLUSION: Hypocaloric
      diet plus orlistat in obese women is superior to diet alone with regard to the
      changes observed in adipokines, CRP, TNFalpha, triglycerides, IGF-1, and
      oxidative stress following intervention.

PMID- 17178702
TI  - Total parathyroidectomy with autotransplantation in patients with renal
      hyperparathyroidism: indications and surgical approach.
AB  - OBJECTIVE: renal hyperparathyroidism (rH) is one of the most serious
      complications in long-term hemodialysis patients. the purpose of this
      retrospective study was the evaluation of the surgical indications, parathyroid
      histology, and the results of total parathyroidectomy with autotransplantation
      (Ptx+At) in patients with rH. DESIGN: the study included 36 patients with rH in
      whom Ptx+At was carried out at the First surgical Department of the Evangelismos
      Hospital over a 5-year period. Indications for Ptx+At were high levels of
      parathyroid hormone (PtH >800 ng/L) associated with hypercalcemia and/or
      hyperphosphatemia, that were refractory to medical treatment, as well as clinical
      effects of rH, including pruritus, bone and joints pain, muscle weakness,
      progression of soft tissue calcification, and spontaneous fractures.
      Ultrasonography, (99m)Tc sestamibi scan and computed tomography were used to
      evaluate the thyroid and parathyroids. RESULTS: there was no mortality related to
      surgery. Preoperative symptoms, serum PtH, serum alkaline phosphatace,
      hyperphosphatemia, and hypercalcemia were improved or normalised in most
      patients. recurrence was observed in one case; this autotransplanted patient
      required resection of transplanted tissue from his forearm. Hypoparathyroidism
      was not recorded. CONCLUSIONS: Ptx+At is a safe option for the treatment of rH
      that is accompanied by low morbidity, mortality, and recurrence rate. It is
      important to identify all parathyroid glands at surgery and to choose adequate
      parathyroid tissue for autograft.

PMID- 17178703
TI  - Iodine 131 treatment for differentiated thyroid carcinoma in patients with end
      stage renal failure: dosimetric, radiation safety, and practical considerations.
AB  - BACKGROUND: Iodine 131 ablation following total thyroidectomy is considered an
      indispensable element of successful treatment of differentiated thyroid carcinoma
      (Dtc). because of the essential role of the kidneys in iodine clearance, (131)I
      therapy of Dtc in patients with end stage renal disease, particularly those
      maintained on haemodialysis, present a number of special features: the (131)I
      activity needs to be modified, the haemodialysis sessions need to be adjusted at
      the time of (131)I therapy, and there are radiation safety considerations during
      dialysis. there is considerable controversy over these crucial questions in the
      reports published so far in the literature, which concern a total of fourteen
      patients. OBJECTIVE: the aim of our study was to present our experience on (131)I
      treatment of 5 Dtc patients with end stage renal disease. DESIGN: the data of 5
      Dtc patients with end stage renal disease, treated with (131)I, were
      retrospectively analysed; four cases were treated for remnant ablation and one
      for locoregional progression. In order to allow for prolonged plasma clearance of
      (131)I, we used a lower activity of radioiodine, reduced to roughly 40-50% of the
      empirically calculated activity used for normal individuals; dialysis sessions
      were performed immediately before and at 48 hours after (131)I administration.
      All patients had (131)I retention measurements performed post dialysis; in two of
      them some additional measurements such as iodine clearances were also performed.
      RESULTS: None of the patients experienced any short-term side effects, while they
      all had undetectable thyroglobulin levels on the first post therapy evaluation
      off thyroxine. (131)I elimination in the first haemodialysis was about 60%. staff
      incidental exposure and (131)I contamination were insignificant. CONCLUSIONS: On
      the basis of our experience, an empiric activity of 40-50% of that used for
      normal individuals appears to be effective as well as safe. these encouraging
      findings are discussed in relation with other reports in the literature.

PMID- 17178704
TI  - A novel splicing mutation in exon 4 (456G>A) of the GH1 gene in a patient with
      congenital isolated growth hormone deficiency.
AB  - Isolated Growth Hormone Deficiency (IGHD) due to GH1 gene defects has a variable
      inheritance pattern: autosomal recessive, autosomal dominant, and X-linked. the
      autosomal dominantly inherited form, IGHD II, is mainly caused by heterozygous
      mutations of splicing around the exon 3/IVs3 boundary region of the GH1 gene
      resulting in exon 3 skipping of transcripts. We have previously reported findings
      on GH1 gene mutations in 28 russian patients with severe congenital IGHD (-3.22+/
      1.2 height sDs at the age of 1yr); five heterozygous dominant negative splice
      site mutations in intron 2, intron 3, and exon 4 of the GH1 gene were identified
      in 32.1% of the cohort. In the present report we describe a novel 456G>A
      heterozygous mutation of splicing of the last base of the 3'-acceptor splice site
      of exon 4 within the GH1 in a 4.2-year old, extremely short (-5.32 height sDs)
      girl with congenital IGHD. the mutation involves a highly conserved GGGgtg
      sequence of the exon 4/IVs4 boundary region of the GH1 gene. the predicted effect
      of the 456 G>A mutation is perturbed splicing with possible skipping of exon 4 of
      the GH1 gene. the novel heterozygous 456 G>A mutation in exon 4 expands the
      spectrum of dominant negative splicing defects within the GH1 gene, responsible
      for congenital IGHD.

PMID- 17178705
TI  - Follicular carcinoma of the thyroid with aggressive metastatic behavior in a
      pregnant woman: report of a case and review of the literature.
AB  - Distant metastases as initial presentation of follicular carcinoma of the thyroid
      is rare, especially in young patients. We report the clinical and pathological
      features of a 33-year old pregnant patient with follicular carcinoma of the
      thyroid who presented with widespread bone and lung metastases at the time of
      diagnosis. the resected tumor had a focal insular component that showed extensive
      vascular invasion spreading beyond the thyroid capsule, and was associated with
      widespread bone and lung metastases. Despite its aggressive behavior, the tumor
      had low mitotic activity and Ki-67 nuclear labeling index. tumor cells showed
      high microvascular density and down-regulation of E-cadherin, a calcium-dependent
      trans-membrane epithelial protein molecule known to promote intercellular
      adhesion. We suggest that architectural differentiation of the tumor and cell
      proliferation rate are not reliable markers of metastatic behavior in this
      particular thyroid neoplasm. Microvascular density and down-regulation of E
      cadherin expression in the tumor should be included among histologic hallmarks of
      metastatic potential. the role of pregnancy in the aggressive behavior of this
      tumor is discussed along with a literature review.

PMID- 17178706
TI  - Papillary thyroid carcinoma producing granulocyte-macrophage colony-stimulating
      factor is associated with neutrophilia and eosinophilia.
AB  - Thyroid tumors producing colony-stimulating factors associated with neutrophilia
      and/or eosinophilia are very rare and almost all of them concern anaplastic
      thyroid cancer. Only one case of papillary thyroid carcinoma associated with
      neutrophilia and one case of medullary thyroid carcinoma associated with
      eosinophilia have been reported. In this report a 72-year old male patient with
      metastatic papillary thyroid carcinoma associated with neutrophilia and
      eosinophilia is described. While investigating the cause of neutrophilia and
      eosinophilia, a blind bone marrow biopsy of the posterior iliac crest was
      performed, which showed infiltration by papillary thyroid carcinoma. High blood
      levels of granulocyte-macrophage colony-stimulating factor (GM-csF) were found
      using an enzyme-linked immunosorbent assay. As other causes of neutrophilia and
      eosinophilia were excluded, we assumed that these were paraneoplastic
      manifestations induced by GM-csF produced by the thyroid tumor. the disease
      progressed rapidly, despite appropriate treatment which included thyroidectomy
      and postoperative radioactive (131)I administration. the patient died 11 months
      after diagnosis because of extensive lung metastasis. Neutrophilia and
      eosinophilia were stable findings, while serum thyroglobulin levels remained
      elevated throughout the follow-up period. to our knowledge, this is the first
      report of a patient with metastatic papillary thyroid carcinoma in whom
      neutrophilia and eosinophilia associated with high circulating levels of GM-csF
      were detected.

PMID- 17178707
TI  - Oskar Minkowski (1858-1931). An outstanding master of diabetes research.
AB  - Oskar Minkowski, a physician of many talents, was an outstanding clinical
      scientist, a brilliant experimental investigator and a prolific medical writer.
      His name is connected with highly important clinical studies and experimental
      probes, all of which significantly contributed to our understanding of the
      pathogenesis of diabetes mellitus after removal of the pancreas (experimental
      pancreatectomy).

PMID- 17178708
TI  - Mass analysis by scanning transmission electron microscopy and electron
      diffraction validate predictions of stacked beta-solenoid model of HET-s prion
      fibrils.
AB  - Fungal prions are infectious filamentous polymers of proteins that are soluble in
      uninfected cells. In its prion form, the HET-s protein of Podospora anserina
      participates in a fungal self/non-self recognition phenomenon called heterokaryon
      incompatibility. Like other prion proteins, HET-s has a so-called "prion domain"
      (its C-terminal region, HET-s-(218-289)) that is responsible for induction and
      propagation of the prion in vivo and for fibril formation in vitro. Prion fibrils
      are thought to have amyloid backbones of polymerized prion domains. A relatively
      detailed model has been proposed for prion domain fibrils of HET-s based on a
      variety of experimental constraints (Ritter, C., Maddelein, M. L., Siemer, A. B.,
      Luhrs, T., Ernst, M., Meier, B. H., Saupe, S. J., and Riek, R. (2005) Nature 435,
      844-848). To test specific predictions of this model, which envisages axial
      stacking of beta-solenoids with two coils per subunit, we examined fibrils by
      electron microscopy. Electron diffraction gave a prominent meridional reflection
      at (0.47 nm)(-1), indicative of cross-beta structure, as predicted. STEM
      (scanning transmission electron microscopy) mass-per-unit-length measurements
      yielded 1.02 +/- 0.16 subunits per 0.94 nm, in agreement with the model
      prediction (1 subunit per 0.94 nm). This is half the packing density of
      approximately 1 subunit per 0.47 nm previously obtained for fibrils of the yeast
      prion proteins, Ure2p and Sup35p, whence it follows that the respective amyloid
      architectures are basically different.

PMID- 17178709
TI  - Glycosylation mediates up-regulation of a potent antiangiogenic and
      proatherogenic protein, thrombospondin-1, by glucose in vascular smooth muscle
      cells.
AB  - Accelerated development of atherosclerotic lesions remains the most frequent and
      dangerous complication of diabetes, accounting for 80% of deaths among diabetics.
      However, our understanding of the pathways mediating glucose-induced gene
      expression in vascular cells remains controversial and incomplete. We have
      identified an intracellular metabolic pathway activated by high glucose in human
      aortic smooth muscle cells that mediates up-regulation of thrombospondin-1 (TSP
      1). TSP-1 is a potent antiangiogenic and proatherogenic protein that may
      represent an important link between diabetes and vascular complications. Using
      different glucose analogs and metabolites sharing distinct, limited metabolic
      steps with glucose, we demonstrated that activation of TSP-1 transcription is
      mediated by the hexosamine pathway of glucose catabolism, possibly resulting in
      modulation of the activity of nuclear proteins activity through their
      glycosylation. Specific inhibitors of glutamine: fructose 6-phosphate
      amidotransferase (GFAT), an enzyme controlling the hexosamine pathway, as well as
      direct inhibitors of protein glycosylation efficiently inhibited TSP-1
      transcription and the activity of a TSP-1 promoter-reporter construct stimulated
      by high glucose. Overexpression of recombinant GFAT resulted in increased TSP-1
      levels. Pharmacological inhibition of GFAT or protein glycosylation inhibited
      increased proliferation of human aortic smooth muscle cells caused by glucose. We
      have demonstrated that the hexosamine metabolic pathway mediates up-regulation of
      TSP-1 by high glucose. Our results suggest that the hexosamine pathway and
      intracellular glycosylation may control important steps in initiation and
      development of atherosclerotic lesions.

PMID- 17178710
TI  - Curcumin opens cystic fibrosis transmembrane conductance regulator channels by a
      novel mechanism that requires neither ATP binding nor dimerization of the
      nucleotide-binding domains.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels are
      essential mediators of salt transport across epithelia. Channel opening normally
      requires ATP binding to both nucleotide-binding domains (NBDs), probable
      dimerization of the two NBDs, and phosphorylation of the R domain. How
      phosphorylation controls channel gating is unknown. Loss-of-function mutations in
      the CFTR gene cause cystic fibrosis; thus, there is considerable interest in
      compounds that improve mutant CFTR function. Here we investigated the mechanism
      by which CFTR is activated by curcumin, a natural compound found in turmeric.
      Curcumin opened CFTR channels by a novel mechanism that required neither ATP nor
      the second nucleotide-binding domain (NBD2). Consequently, this compound potently
      activated CF mutant channels that are defective for the normal ATP-dependent mode
      of gating (e.g. G551D and W1282X), including channels that lack NBD2. The
      stimulation of NBD2 deletion mutants by curcumin was strongly inhibited by ATP
      binding to NBD1, which implicates NBD1 as a plausible activation site. Curcumin
      activation became irreversible during prolonged exposure to this compound
      following which persistently activated channels gated dynamically in the absence
      of any agonist. Although CFTR activation by curcumin required neither ATP binding
      nor heterodimerization of the two NBDs, it was strongly dependent on prior
      channel phosphorylation by protein kinase A. Curcumin is a useful functional
      probe of CFTR gating that opens mutant channels by circumventing the normal
      requirements for ATP binding and NBD heterodimerization. The phosphorylation
      dependence of curcumin activation indicates that the R domain can modulate
      channel opening without affecting ATP binding to the NBDs or their
      heterodimerization.

PMID- 17178711
TI  - A novel cell-permeable antioxidant peptide, SS31, attenuates ischemic brain
      injury by down-regulating CD36.
AB  - Oxidative stress is implicated in the pathogenesis of ischemia/reperfusion
      injury. Recently, we demonstrated that activation of CD36, a class B scavenger
      receptor, mediates free radical production and tissue injury in cerebral ischemia
      (1). Oxidized low density lipoproteins (oxLDL) are among the ligands that bind to
      CD36 and are elevated in acute cerebral infarction. SS31 is a cell-permeable
      antioxidant peptide that reduces intracellular free radicals and inhibits LDL
      oxidation/lipid peroxidation (2). The current study was designed to investigate
      whether treatment with SS31 normalizes ischemia-induced redox changes and
      attenuates CD36-mediated tissue injury. C57BL/6 mice were subjected to transient
      middle cerebral artery occlusion (MCAO). Redox status and infarct volume were
      measured in animals treated with either saline or SS31. Oxidative stress induced
      by ischemia/reperfusion profoundly depleted glutathione (GSH) concentrations in
      the ipsilateral cortex and striatum. Treating mice with SS31 immediately after
      reperfusion significantly attenuated ischemia-induced GSH depletion in the cortex
      and reduced infarct size. By contrast, the protective effect of SS31 was absent
      in CD36 knock-out mice, indicating that SS31 is acting through inhibition of
      CD36. Treating C57BL/6 mice with SS31 reduced CD36 expression in postischemic
      brain and mouse peritoneal macrophages (MPM). Further in vitro studies revealed
      that SS31 attenuated oxLDL-induced CD36 expression and foam cell formation in
      MPM. These in vivo and in vitro studies indicate that the down-regulation of CD36
      by novel class antioxidant peptides may be a useful strategy to treat ischemic
      stroke victims.

PMID- 17178712
TI  - Analysis of nucleocytoplasmic trafficking of the HuR ligand APRIL and its
      influence on CD83 expression.
AB  - Dendritic cells (DC) are the most potent antigen-presenting cells of the immune
      system and are able to sensitize even naive T cells. Mature DC are characterized
      by expression of CD83, a surface molecule that is proposed to be involved in
      efficient T cell activation. It has been recently shown that CD83 mRNA is
      transported from the nucleus to the cytoplasm in a HuR- and CRM1-dependent
      manner. Therefore we here investigated the impact of two known protein ligands of
      HuR, pp32 and APRIL, on CD83 expression. Both pp32 (ANP32A) and APRIL (ANP32B)
      are shuttle proteins, and it has been reported earlier that these HuR ligands can
      act as adaptors that link HuR and the CRM1-specific nuclear export pathway. By
      employing RNA interference (RNAi) technology we demonstrate that pp32 is
      dispensable for CD83 expression, whereas APRIL contributes to the nuclear export
      and subsequent translation of CD83 mRNA. Furthermore, we have determined the
      nuclear import signal (NLS) as well as the nuclear export signal (NES) of human
      APRIL. Moreover, we analyzed the status of phosphorylation of endogenous APRIL
      and identified threonine 244 to be an as yet unrecognized phosphate acceptor.
      Finally, we were able to show that phosphorylation of this specific amino acid
      residue regulates the nuclear export of APRIL. In sum, we report here the signal
      sequences in APRIL that mediate its intracellular trafficking and provide
      evidence that this protein ligand of HuR is an important player in the post
      transcriptional regulation of CD83 expression by affecting the nucleocytoplasmic
      translocation of CD83 mRNA.

PMID- 17178713
TI  - A comprehensive interaction map of the human survival of motor neuron (SMN)
      complex.
AB  - Assembly of the Sm-class of U-rich small nuclear ribonucleoprotein particles (U
      snRNPs) is a process facilitated by the macromolecular survival of motor neuron
      (SMN) complex. This entity promotes the binding of a set of factors, termed
      LSm/Sm proteins, onto snRNA to form the core structure of these particles. Nine
      factors, including the SMN protein, the product of the spinal muscular atrophy
      (SMA) disease gene, Gemins 2-8 and unrip have been identified as the major
      components of the SMN complex. So far, however, only little is known about the
      architecture of this complex and the contribution of individual components to its
      function. Here, we present a comprehensive interaction map of all core components
      of the SMN complex based upon in vivo and in vitro methods. Our studies reveal a
      modular composition of the SMN complex with the three proteins SMN, Gemin8, and
      Gemin7 in its center. Onto this central building block the other components are
      bound via multiple interactions. Furthermore, by employing a novel assay, we were
      able to reconstitute the SMN complex from individual components and confirm the
      interaction map. Interestingly, SMN protein carrying an SMA-causing mutation was
      severely impaired in formation of the SMN complex. Finally, we show that the
      peripheral component Gemin5 contributes an essential activity to the SMN complex,
      most likely the transfer of Sm proteins onto the U snRNA. Collectively, the data
      presented here provide a basis for the detailed mechanistic and structural
      analysis of the assembly machinery of U snRNPs.

PMID- 17178714
TI  - DeltaF508 mutation results in impaired gastric acid secretion.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is recognized as a
      multifunctional protein that is involved in Cl(-) secretion, as well as acting as
      a regulatory protein. In order for acid secretion to take place a complex
      interaction of transport proteins and channels must occur at the apical pole of
      the parietal cell. Included in this process is at least one K(+) and Cl(-)
      channel, allowing for both recycling of K(+) for the H,K-ATPase, and Cl(-)
      secretion, necessary for the generation of concentrated HCl in the gastric gland
      lumen. We have previously shown that an ATP-sensitive potassium channel (K(ATP))
      is expressed in parietal cells. In the present study we measured secretagogue
      induced acid secretion from wild-type and DeltaF508-deficient mice in isolated
      gastric glands and whole stomach preparations. Secretagogue-induced acid
      secretion in wild-type mouse gastric glands could be significantly reduced with
      either glibenclamide or the specific inhibitor CFTR-inh172. In DeltaF508
      deficient mice, however, histamine-induced acid secretion was significantly less
      than in wild-type mice. Furthermore, immunofluorescent localization of
      sulfonylurea 1 and 2 failed to show expression of a sulfonylurea receptor in the
      parietal cell, thus further implicating CFTR as the ATP-binding cassette
      transporter associated with the K(ATP) channels. These results demonstrate a
      regulatory role for the CFTR protein in normal gastric acid secretion.

PMID- 17178715
TI  - Targeting and stability of Na/Ca exchanger 1 in cardiomyocytes requires direct
      interaction with the membrane adaptor ankyrin-B.
AB  - Na/Ca exchanger activity is important for calcium extrusion from the
      cardiomyocyte cytosol during repolarization. Animal models exhibiting altered
      Na/Ca exchanger expression display abnormal cardiac phenotypes. In humans,
      elevated Na/Ca exchanger expression/activity is linked with pathophysiological
      conditions including arrhythmia and heart failure. Whereas the molecular
      mechanisms underlying Na/Ca exchanger biophysical properties are widely studied
      and generally well characterized, the cellular pathways and molecular partners
      underlying the specialized membrane localization of Na/Ca exchanger in cardiac
      tissue are essentially unknown. In this report, we present the first direct
      evidence for a protein pathway required for Na/Ca exchanger localization and
      stability in primary cardiomyocytes. We define the minimal structural
      requirements on ankyrin-B for direct Na/Ca exchanger interactions. Moreover,
      using ankyrin-B mutants that lack Na/Ca exchanger binding activity, and primary
      cardiomyocytes with reduced ankyrin-B expression, we demonstrate that direct
      interaction with the membrane adaptor ankyrin-B is required for the localization
      and post-translational stability of Na/Ca exchanger 1 in neonatal mouse
      cardiomyocytes. These results raise exciting new questions regarding potentially
      dynamic roles for ankyrin proteins in the biogenesis and maintenance of
      specialized membrane domains in excitable cells.

PMID- 17178716
TI  - Hxk2 regulates the phosphorylation state of Mig1 and therefore its
      nucleocytoplasmic distribution.
AB  - Mig1 and Hxk2 are two major mediators of glucose repression in Saccharomyces
      cerevisiae. However, the mechanism by which Hxk2 participates in the glucose
      repression signaling pathway is not completely understood. Recently, it has been
      demonstrated that Hxk2 interacts with Mig1 to generate a repressor complex
      located in the nucleus of S. cerevisiae. However, the mechanism by which Mig1
      favors the presence of Hxk2 in the nucleus is not clear, and the function of Hxk2
      at the nuclear repressor complex level is still unknown. Here, we report that
      serine 311 of Mig1 is a critical residue for interaction with Hxk2 and that this
      interaction is regulated by glucose. Our findings suggest that Snf1 interacts
      constitutively with the Hxk2 component of the repressor complex at high and low
      glucose conditions. Furthermore, we show that Snf1 binds to Mig1 under low
      glucose conditions and that binding is largely abolished after a shift to high
      glucose medium. We found that phosphorylation of serine 311 of Mig1 by Snf1
      kinase is essential for Mig1 protein nuclear export and derepression of the SUC2
      gene in glucose-limited cells. These results allow postulating that the Hxk2
      operates by interacting both with Mig1 and Snf1 to inhibit the Mig1
      phosphorylation at serine 311 during high glucose grown.

PMID- 17178717
TI  - Flagellin contamination of recombinant heat shock protein 70 is responsible for
      its activity on T cells.
AB  - Heat shock proteins (Hsp) 60 and 70 have been intensively studied for their
      ability to activate innate immunity. Heat shock proteins had been shown to induce
      the activation of dendritic cells, T cells, and B cells. However, the possible
      contamination of endotoxin in heat shock protein preparations makes their
      function as an activator of immune system ambiguous. Here, we examined the
      ability of bacterial Hsp60 and Hsp70 to activate Jurkat T cells and primary T
      cells. We found that Burkholderia pseudomallei Hsp70 and Mycobacterium
      tuberculosis Hsp70 could costimulate Jurkat T cells to make IL-2 and signal
      through TLR5. This costimulatory activity is not due to endotoxin or contaminants
      signaling via TLR2 nor TLR4. However, recombinant Hsp70 expressed in Escherichia
      coli DeltafliC strain completely lost its ability to costimulate T cells. Thus,
      the activation of T cells by recombinant Hsp70 is ascribed to flagellin
      contamination.

PMID- 17178718
TI  - Inhibition of APCCdh1 activity by Cdh1/Acm1/Bmh1 ternary complex formation.
AB  - The anaphase-promoting complex (APC) is an essential E3 ubiquitin ligase
      responsible for catalyzing proteolysis of key regulatory proteins in the cell
      cycle. Cdh1 is a co-activator of the APC aiding in the onset and maintenance of
      G(1) phase, whereas phosphorylation of Cdh1 at the end of G(1) phase by cyclin
      dependent kinases assists in the inactivation of APC(Cdh1). Here, we suggest
      additional components are involved in the inactivation of APC(Cdh1) independent
      of Cdh1 phosphorylation. We have identified proteins known as Acm1 and Bmh1,
      which bind and form a ternary complex with Cdh1. The presence of phosphorylated
      Acm1 is critical for the ternary complex formation, and Acm1 is predominantly
      expressed in S phase when APC(Cdh1) is inactive. The assembly of the ternary
      complex inhibits ubiquitination of Clb2 in vitro by blocking the interaction of
      Cdh1 with Clb2. In vivo, lethality caused by overexpression of constitutively
      active Cdh1 is rescued by overexpression of Acm1. Partially phosphorylated Cdh1
      in the absence of ACM1 still binds to and activates the APC. However, the
      addition of Acm1 decreases Clb2 ubiquitination when using either phosphorylated
      or nonphosphorylated Cdh1. Taken together, our results suggest an additional
      inactivation mechanism exists for APC(Cdh1) that is independent of Cdh1
      phosphorylation.

PMID- 17178719
TI  - Functional characterization of desaturases involved in the formation of the
      terminal double bond of an unusual 16:3Delta(9,12,150) fatty acid isolated from
      Sorghum bicolor root hairs.
AB  - Sorgoleone, produced in root hair cells of sorghum (Sorghum bicolor), is likely
      responsible for much of the allelopathic properties of sorghum root exudates
      against broadleaf and grass weeds. Previous studies suggest that the biosynthetic
      pathway of this compound initiates with the synthesis of an unusual 16:3 fatty
      acid possessing a terminal double bond. The corresponding fatty acyl-CoA serves
      as a starter unit for polyketide synthases, resulting in the formation of 5
      pentadecatrienyl resorcinol. This resorcinolic intermediate is then methylated by
      an S-adenosylmethionine-dependent O-methyltransferase and subsequently
      dihydroxylated, yielding the reduced (hydroquinone) form of sorgoleone. To
      characterize the corresponding enzymes responsible for the biosynthesis of the
      16:3 fatty acyl-CoA precursor, we identified and cloned three putative fatty acid
      desaturases, designated SbDES1, SbDES2, and SbDES3, from an expressed sequence
      tag (EST) data base prepared from isolated root hairs. Quantitative real-time RT
      PCR analyses revealed that these three genes were preferentially expressed in
      sorghum root hairs where the 16:2 and 16:3 fatty acids were exclusively
      localized. Heterologous expression of the cDNAs in Saccharomyces cerevisiae
      revealed that recombinant SbDES2 converted palmitoleic acid (16:1Delta(9)) to
      hexadecadienoic acid (16:2Delta(9,12)), and that recombinant SbDES3 was capable
      of converting hexadecadienoic acid into hexadecatrienoic acid
      (16:3Delta(9,12,15)). Unlike other desaturases reported to date, the double bond
      introduced by SbDES3 occurred between carbons 15 and 16 resulting in a terminal
      double bond aliphatic chain. Collectively, the present results strongly suggest
      that these fatty acid desaturases represent key enzymes involved in the
      biosynthesis of the allelochemical sorgoleone.

PMID- 17178720
TI  - Global regulation of photosynthesis and respiration by FnrL: the first two
      targets in the tetrapyrrole pathway.
AB  - Fnr is a regulator that controls the expression of a variety of genes in response
      to oxygen limitation in bacteria. To assess the role of Fnr in photosynthesis in
      Rubrivivax gelatinosus, a strain carrying a null mutation in fnrL was
      constructed. It was unable to grow anaerobically in the light, but, intriguingly,
      it was able to produce photosynthetic complexes under high oxygenation
      conditions. The mutant lacked all c-type cytochromes normally detectable in
      microaerobically-grown wild type cells and accumulated coproporphyrin III. These
      data suggested that the pleiotropic phenotype observed in FNR is primarily due to
      the control at the level of the HemN oxygen-independent coproporphyrinogen III
      dehydrogenase. hemN expression in trans partially suppressed the FNR phenotype,
      as it rescued heme and cytochrome syntheses. Nevertheless, these cells were
      photosynthetically deficient, and pigment analyses showed that they were blocked
      at the level of Mg(2+)-protoporphyrin monomethyl ester. Expression of both hemN
      and bchE in the FNR mutant restored synthesis of Mg(2+)-protochlorophyllide. We,
      therefore, conclude that FnrL controls respiration by regulating hemN expression
      and controls photosynthesis by regulating both hemN and bchE expression. A
      comprehensive picture of the control points of microaerobic respiration and
      photosynthesis by FnrL is provided, and the prominent role of this factor in
      activating alternative gene programs after reduction of oxygen tension in
      facultative aerobes is discussed.

PMID- 17178722
TI  - Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell
      growth.
AB  - JAK2(V617F), a mutant of tyrosine kinase JAK2, is found in most patients with
      polycythemia vera (PV) and a substantial proportion of patients with idiopathic
      myelofibrosis or essential thrombocythemia. The JAK2 mutant displays a much
      increased kinase activity and generates a PV-like phenotype in mouse bone marrow
      transplant models. This study shows that the anti-cancer drug erlotinib (Tarceva)
      is a potent inhibitor of JAK2(V617F) activity. In vitro colony culture assays
      revealed that erlotinib at micro-molar concentrations effectively suppresses the
      growth and expansion of PV hematopoietic progenitor cells while having little
      effect on normal cells. Furthermore, JAK2(V617F)-positive cells from PV patients
      show greater susceptibility to the inhibitor than their negative counterparts.
      Similar inhibitory effects were found with the JAK2(V617F)-positive human
      erythroleukemia HEL cell line. These data suggest that erlotinib may be used for
      treatment of JAK2(V617F)-positive PV and other myeloproliferative disorders.

PMID- 17178723
TI  - Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-kappa
      B activation.
AB  - Innate immune response to viral infection is often triggered by Toll-like
      receptor 3 (TLR3)-mediated signaling by double-stranded (ds) RNA, which
      culminates in the activation of the transcription factor NF-kappaB and induction
      of NF-kappaB-driven genes. We demonstrated that dsRNA-induced phosphorylation of
      two specific tyrosine residues, 759 and 858, of TLR3 was necessary and sufficient
      for complete activation of the NF-kappaB pathway. When Tyr-759 of TLR3 was
      mutated, gene induction was inhibited, although NF-kappaB was partially
      activated. It was released from IkappaB and translocated to the nucleus but
      failed to bind to the kappaB site of the target A20 gene promoter. This defect
      could be attributed to incomplete phosphorylation of the RelA (p65) subunit of NF
      kappaB, as revealed by two-dimensional gel analyses of p65, isolated from dsRNA
      treated cells expressing either wild type TLR3 or the Tyr-759 --> Phe mutant
      TLR3. Thus, two phosphotyrosine residues of TLR3 activate two distinct pathways,
      one leading to NF-kappaB release and the other leading to its phosphorylation.

PMID- 17178721
TI  - Protein inhibitor of activated STAT1 interacts with and up-regulates activities
      of the pro-proliferative transcription factor Kruppel-like factor 5.
AB  - Kruppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor
      that regulates proliferation of various cell types, including fibroblasts, smooth
      muscle cells, and intestinal epithelial cells. To identify proteins that interact
      with KLF5, we performed a yeast two-hybrid screen of a 17-day mouse embryo cDNA
      library with KLF5 as bait. The screen revealed 21 preys clustered in four groups
      as follows: proteins mediating gene expression, metabolism, trafficking, and
      signaling. Among them was protein inhibitor of activated STAT1 (PIAS1), a small
      ubiquitin-like modifier (SUMO) ligase that regulates transcription factors
      through SUMOylation or physical interaction. Association between PIAS1 and KLF5
      was verified by co-immunoprecipitation. Structural determination showed that the
      acidic domain of PIAS1 bound to both the amino- and carboxyl-terminal regions of
      KLF5 and that this interaction was inhibited by the amino terminus of PIAS1.
      Indirect immunofluorescence demonstrated that PIAS1 and KLF5 co-localized to the
      nucleus. Furthermore, the PIAS1-KLF5 complex was co-localized with the TATA
      binding protein and was enriched in RNA polymerase II foci. Transient
      transfection of COS-7 cells by PIAS1 and KLF5 significantly increased the steady
      state protein levels of each other. Luciferase reporter and chromatin
      immunoprecipitation assays showed that PIAS1 significantly activated the
      promoters of KLF5 and PIAS1 and synergistically increased the transcriptional
      activity of KLF5 in activating the cyclin D1 and Cdc2 promoters. Importantly,
      PIAS1 increased the ability of KLF5 to enhance cell proliferation in transfected
      cells. These results indicate that PIAS1 is a functional partner of KLF5 and
      enhances the ability of KLF5 to promote proliferation.

PMID- 17178724
TI  - The scaffolding adapter Gab1 mediates vascular endothelial growth factor
      signaling and is required for endothelial cell migration and capillary formation.
AB  - Vascular endothelial growth factor (VEGF) is involved in the promotion of
      endothelial cell proliferation, migration, and capillary formation. These
      activities are mainly mediated by the VEGFR2 receptor tyrosine kinase that upon
      stimulation, promotes the activation of numerous proteins including phospholipase
      Cgamma (PLCgamma), phosphatidylinositol 3-kinase (PI3K), Akt, Src, and ERK1/2.
      However, the VEGFR2-proximal signaling events leading to the activation of these
      targets remain ill defined. We have identified the Gab1 adapter as a novel
      tyrosine-phosphorylated protein in VEGF-stimulated cells. In bovine aortic
      endothelial cells, Gab1 associates with VEGFR2, Grb2, PI3K, SHP2, Shc, and
      PLCgamma, and its overexpression enhances VEGF-dependent cell migration.
      Importantly, silencing of Gab1 using small interfering RNAs leads to the impaired
      activation of PLCgamma, ERK1/2, Src, and Akt; blocks VEGF-induced endothelial
      cell migration; and perturbs actin reorganization and capillary formation. In
      addition, co-expression of VEGFR2 with Gab1 mutants unable to bind SHP2 or PI3K
      in human embryonic kidney 293 cells and bovine aortic endothelial cells mimics
      the defects observed in Gab1-depleted cells. Our work thus identifies Gab1 as a
      novel critical regulatory component of endothelial cell migration and capillary
      formation and reveals its key role in the activation of VEGF-evoked signaling
      pathways required for angiogenesis.

PMID- 17178725
TI  - Structural basis of peroxide-mediated changes in human hemoglobin: a novel
      oxidative pathway.
AB  - Hydrogen peroxide (H(2)O(2)) triggers a redox cycle between ferric and ferryl
      hemoglobin (Hb) leading to the formation of a transient protein radical and a
      covalent hemeprotein cross-link. Addition of H(2)O(2) to highly purified human
      hemoglobin (HbA(0)) induced structural changes that primarily resided within beta
      subunits followed by the internalization of the heme moiety within alpha
      subunits. These modifications were observed when an equal molar concentration of
      H(2)O(2) was added to HbA(0) yet became more abundant with greater concentrations
      of H(2)O(2). Mass spectrometric and amino acid analysis revealed for the first
      time that betaCys-93 and betaCys-112 were oxidized extensively and irreversibly
      to cysteic acid when HbA(0) was treated with H(2)O(2). Oxidation of further amino
      acids in HbA(0) exclusive to the beta-globin chain included modification of
      betaTrp-15 to oxyindolyl and kynureninyl products as well as betaMet-55 to
      methionine sulfoxide. These findings may therefore explain the premature collapse
      of the beta subunits as a result of the H(2)O(2) attack. Analysis of a tryptic
      digest of the main reversed phase-high pressure liquid chromatography fraction
      revealed two alpha-peptide fragments (alpha128-alpha139) and a heme moiety with
      the loss of iron, cross-linked between alphaSer-138 and the porphyrin ring. The
      novel oxidative pathway of HbA(0) modification detailed here may explain the
      diverse oxidative, toxic, and potentially immunogenic effects associated with the
      release of hemoglobin from red blood cells during hemolytic diseases and/or when
      cell-free Hb is used as a blood substitute.

PMID- 17178726
TI  - Epac-mediated activation of phospholipase C(epsilon) plays a critical role in
      beta-adrenergic receptor-dependent enhancement of Ca2+ mobilization in cardiac
      myocytes.
AB  - Recently we demonstrated that PLC(epsilon) plays an important role in beta
      adrenergic receptor (betaAR) stimulation of Ca(2+)-induced Ca(2+) release (CICR)
      in cardiac myocytes. Here we have reported for the first time that a pathway
      downstream of betaAR involving the cAMP-dependent Rap GTP exchange factor, Epac,
      and PLC(epsilon) regulates CICR in cardiac myocytes. To demonstrate a role for
      Epac in the stimulation of CICR, cardiac myocytes were treated with an Epac
      selective cAMP analog, 8-4-(chlorophenylthio)-2'-O-methyladenosine-3',5'
      monophosphate (cpTOME). cpTOME treatment increased the amplitude of electrically
      evoked Ca(2+) transients, implicating Epac for the first time in cardiac CICR.
      This response is abolished in PLC(epsilon)(-/-) cardiac myocytes but rescued by
      transduction with PLC(epsilon), indicating that Epac is upstream of PLC(epsilon).
      Furthermore, transduction of PLC(epsilon)(+/+) cardiac myocytes with a Rap
      inhibitor, RapGAP1, significantly inhibited isoproterenol-dependent CICR. Using a
      combination of cpTOME and PKA-selective activators and inhibitors, we have shown
      that betaAR-dependent increases in CICR consist of two independent components
      mediated by PKA and the novel Epac/(epsilon) pathway. We also show that
      Epac/PLC(epsilon)-dependent effects on CICR are independent of sarcoplasmic
      reticulum loading and Ca(2+) clearance mechanisms. These data define a novel
      endogenous PKA-independent betaAR-signaling pathway through cAMP-dependent Epac
      activation, Rap, and PLC(epsilon) that enhances intracellular Ca(2+) release in
      cardiac myocytes.

PMID- 17178727
TI  - Significance of the N-terminal domain for the function of chloroplast cpn20
      chaperonin.
AB  - Chaperonins cpn60 and cpn10 are essential proteins involved in cellular protein
      folding. Plant chloroplasts contain a unique version of the cpn10 co-chaperonin,
      cpn20, which consists of two homologous cpn10-like domains (N-cpn20 and C-cpn20)
      that are connected by a short linker region. Although cpn20 seems to function
      like other single domain cpn10 oligomers, the structure and specific functions of
      the domains are not understood. We mutated amino acids in the "mobile loop"
      regions of N-cpn20, C-cpn20 or both: a highly conserved glycine, which was shown
      to be important for flexibility of the mobile loop, and a leucine residue shown
      to be involved in binding of co-chaperonin to chaperonin. The mutant proteins
      were purified and their oligomeric structure validated by gel filtration, native
      gel electrophoresis, and circular dichroism. Functional assays of protein
      refolding and inhibition of GroEL ATPase both showed (i) mutation of the
      conserved glycine reduced the activity of cpn20, whether in N-cpn20 (G32A) or C
      cpn20 (G130A). The same mutation in the bacterial cpn10 (GroES G24A) had no
      effect on activity. (ii) Mutations in the highly conserved leucine of N-cpn20
      (L35A) and in the corresponding L27A of GroES resulted in inactive protein. (iii)
      In contrast, mutant L133A, in which the conserved leucine of C-cpn20 was altered,
      retained 55% activity. We conclude that the structure of cpn20 is much more
      sensitive to alterations in the mobile loop than is the structure of GroES.
      Moreover, only N-cpn20 is necessary for activity of cpn20. However, full and
      efficient functioning requires both domains.

PMID- 17178728
TI  - Propionyl-L-carnitine reduces proliferation and potentiates Bax-related apoptosis
      of aortic intimal smooth muscle cells by modulating nuclear factor-kappaB
      activity.
AB  - Propionyl-l-carnitine (PLC) has been introduced among the therapeutic approaches
      of peripheral arterial disease, and more recently, an increase of intimal cell
      apoptosis has been demonstrated to contribute to its effectiveness in rabbit
      carotid postinjury myointimal hyperplasia prevention. How PLC mediates these
      effects on vascular smooth muscle cells (SMCs) remains poorly understood. We
      investigated the role of NF-kappaB in PLC-induced arterial remodeling. In vivo,
      daily PLC treatment 15 days after injury resulted in a reduction of relative rat
      aortic intimal volume, an increase of apoptosis, Bax up-regulation without
      changing the Bcl-2 level, and a reduction of NF-kappaB, vascular cell adhesion
      molecule-1, monocyte chemotactic protein-1, and survivin in myointimal thickening
      compared with controls. In the presence of 10% serum, a reduced G(1) --> S phase
      progression preceded PLC-induced intimal cell apoptosis; in 0.1% serum cultures,
      in a dose-dependent manner, PLC rapidly induced intimal cell apoptosis and
      reduced p65, p50, IAP-1, and IAP-2 expression. Inhibiting NF-kappaB activation
      through SN50 increased apoptotic rate and Bax expression in intimal but not in
      medial SMCs, and successive PLC treatment failed to induce a further increase in
      apoptotic rate. Bax antisense oligodeoxynucleotide reduced PLC-induced intimal
      cell apoptosis and cytochrome c release. The PLC-induced attenuation of NF-kappaB
      activity in intimal cells was also due to the increase of IkappaB-alpha
      bioavailability, as the result of a parallel induction of IkappaB-alpha synthesis
      and reduction of phosphorylation and degradation. Collectively, these findings
      document that NF-kappaB activity inhibition contributes to PLC-induced
      proliferative arrest and Bax-related apoptosis of intimal SMCs.

PMID- 17178730
TI  - Characterization of the pH-dependent interaction between the gap junction protein
      connexin43 carboxyl terminus and cytoplasmic loop domains.
AB  - A prevailing view regarding the regulation of connexin43 (Cx43) gap junction
      channels is that, upon intracellular acidification, the carboxyl-terminal domain
      (Cx43CT) moves toward the channel opening to interact with specific residues
      acting as a receptor site. Previous studies have demonstrated a direct, pH
      dependent interaction between the Cx43CT and a Cx43 cytoplasmic loop (Cx43CL)
      peptide. This interaction was dependent on alpha-helical formation for the
      peptide in response to acidification; more recent studies have shown that
      acidification also induces Cx43CT dimerization. Whether Cx43CT dimerization is an
      important structural component in Cx43 regulation remains to be determined. Here
      we used an assortment of complimentary biophysical techniques to characterize the
      binding of Cx43CT or its mutants to itself and/or to a more native-like Cx43CL
      construct (Cx43CL(100-155), residues 100-155). Our studies expand the observation
      that specific Cx43CT domains are important for dimerization. We further show that
      properties of the Cx43CL(100-155) are different from those of the Cx43CL peptide;
      solvent acidification leads to Cx43CL(100-155) oligomerization and a change in
      the stoichiometry and binding affinity for the Cx43CT. Homo-Cx43CT and Cx43CL(100
      155) oligomerization as well as the Cx43CT/Cx43CL(100-155) interaction can occur
      under in vivo conditions; moreover, we show that Cx43CL(100-155) strongly affects
      resonance peaks corresponding to Cx43CT residues Arg-376-Asp-379 and Asn-343-Lys
      346. Overall, our data indicate that many of the sites involved in Cx43CT
      dimerization are also involved in the Cx43CT/Cx43CL interaction; we further
      propose that chemically induced Cx43CT and Cx43CL oligomerization is important
      for the interaction between these cytoplasmic domains, which leads to chemically
      induced gating of Cx43 channels.

PMID- 17178729
TI  - Kinetic analysis of tubulin assembly in the presence of the microtubule
      associated protein TOGp.
AB  - The microtubule-associated protein TOGp, which belongs to a widely distributed
      protein family from yeasts to humans, is highly expressed in human tumors and
      brain tissue. From purified components we have determined the effect of TOGp on
      thermally induced tubulin association in vitro in the presence of 1 mm GTP and
      3.4 m glycerol. Physicochemical parameters describing the mechanism of tubulin
      polymerization were deduced from the kinetic curves by application of the
      classical theoretical models of tubulin assembly. We have calculated from the
      polymerization time curves a range of parameters characteristic of nucleation,
      elongation, or steady state phase. In addition, the tubulin subunits turnover at
      microtubule ends was deduced from tubulin GTPase activity. For comparison,
      parallel experiments were conducted with colchicine and taxol, two drugs active
      on microtubules and with tau, a structural microtubule-associated protein from
      brain tissue. TOGp, which decreases the nucleus size and the tenth time of the
      reaction (the time required to produce 10% of the final amount of polymer),
      shortens the nucleation phase of microtubule assembly. In addition, TOGp favors
      microtubule formation by increasing the apparent first order rate constant of
      elongation. Moreover, TOGp increases the total amount of polymer by decreasing
      the tubulin critical concentration and by inhibiting depolymerization during the
      steady state of the reaction.

PMID- 17178731
TI  - hPEBP4 resists TRAIL-induced apoptosis of human prostate cancer cells by
      activating Akt and deactivating ERK1/2 pathways.
AB  - The treatment options available for prostate cancer are limited because of its
      resistance to therapeutic agents. Thus, a better understanding of the underlying
      mechanisms of the resistance of prostate cancer will facilitate the discovery of
      more efficient treatment protocols. Human phosphatidylethanolamine-binding
      protein 4 (hPEBP4) is recently identified by us as an anti-apoptotic molecule and
      a potential candidate target for breast cancer treatment. Here we found the
      expression levels of hPEBP4 were positively correlated with the severity of
      clinical prostate cancer. Furthermore, hPEBP4 was not expressed in TRAIL
      sensitive DU145 prostate cancer cells, but was highly expressed in TRAIL
      resistant LNCaP cells, which show highly activated Akt. Interestingly, hPEBP4
      overexpression in TRAIL-sensitive DU145 cells promoted Akt activation but
      inhibited ERK1/2 activation. The hPEBP4-overexpressing DU145 cells became
      resistant to TRAIL-induced apoptosis consequently, which could be reversed by
      PI3K inhibitors. In contrast, silencing of hPEBP4 in TRAIL-resistant LNCaP cells
      inhibited Akt activation but increased ERK1/2 activation, resulting in their
      sensitivity to TRAIL-induced apoptosis that was restored by the MEK1 inhibitor.
      Therefore, hPEBP4 expression in prostate cancer can activate Akt and deactivate
      ERK1/2 signaling, leading to TRAIL resistance. We also demonstrated that hPEBP4
      mediated resistance to TRAIL-induced apoptosis occurred downstream of caspase-8
      and at the level of BID cleavage via the regulation of Akt and ERK pathways, and
      that hPEBP4-regulated ERK deactivation was upstream of Akt activation in prostate
      cancer cells. Considering that hPEBP4 confers cellular resistance to TRAIL
      induced apoptosis and is abundantly expressed in poorly differentiated prostate
      cancer, silencing of hPEBP4 suggests a promising approach for prostate cancer
      treatment.

PMID- 17178734
TI  - Hyponatraemia in adults with community-acquired bacterial meningitis.
AB  - BACKGROUND: Hyponatraemia in adults with bacterial meningitis has been described
      as a common complication, but its true prevalence and clinical importance are
      unknown. AIM: To investigate the prevalence, clinical characteristics and
      consequences of hyponatraemia in bacterial meningitis in adults. DESIGN:
      Nationwide observational cohort study. METHODS: We prospectively assessed the
      prevalence and clinical characteristics of hyponatraemia among 696 adults with
      community-acquired bacterial meningitis. Symptoms and signs on admission, blood
      and CSF test results, radiological examinations and complications during
      admission were recorded. RESULTS: Sodium levels were determined at admission in
      685/696 episodes of bacterial meningitis (98%). Hyponatraemia (<135 mmol/l) was
      seen in 208/685 (30%) and was classified as severe (<130 mmol/l) in 38 (6%).
      Hyponatraemia developed during admission in an additional 53 episodes.
      Hyponatraemia was not associated with an increase in symptoms, with complications
      or with unfavourable outcome. Treatment for hyponatraemia was initiated in 16% of
      episodes, but did not influence its duration. DISCUSSION: Hyponatraemia appears
      both common and benign in adults with bacterial meningitis. In cases of severe
      hyponatraemia, we suggest the use of fluid maintenance therapy.

PMID- 17178736
TI  - The predictive value of ultrasound findings in the management of thyroid nodules.
AB  - BACKGROUND: Thyroid nodules are a common medical problem, but whether fine-needle
      aspiration cytology (FNAC) is mandated for smaller non-palpable nodules, is
      controversial. AIM: To evaluate whether ultrasonographic features of thyroid
      nodules are associated with histological malignancy, and to identify useful
      criteria for clinical decision-making. DESIGN: Prospective observational study.
      METHODS: From January 1991 to September 2004, 5198 patients were referred to our
      hospital for ultrasound evaluation of thyroid nodules. Overall, 7455 nodules
      (diameters from 6 to 100 mm) were examined; 2865 (38.4%) were <10 mm in diameter.
      All patients with suspicious or malignant cytology underwent surgery. RESULTS: Of
      the 349 nodules undergoing surgery, 284 were malignant. The prevalence of cancer
      was slightly higher in nodules>or=10 mm in diameter vs. those<10 mm (5.5% vs.
      3.0%, p<0.01). However, histological type and local aggressiveness were largely
      independent of nodule size. Microcalcifications (72.2% vs. 28.7%; p<0.001; OR
      6.4, 95%CI 4.9-8.4), blurred margins (52.8% vs. 18.8%; p<0.001; OR 4.8, 95%CI 3.8
      6.1), solid hypoechoic appearance (80.6% vs. 52.4%; p<0.001; OR 3.8, 95%CI 2.8
      5.1), size>or=10 mm (77.4% vs. 64.9%; p<0.001; OR 1.9, 95%CI 1.4-2.5) and
      intranodular vascular pattern type 2 (61.6% vs. 49.7%; p<0.001; OR 1.6, 95%CI 1.2
      2.0) were all significantly more frequent in malignant than in benign nodules.
      These associations were similar when large and small nodules were analysed
      separately. DISCUSSION: No single parameter, including nodule size,
      satisfactorily identifies a subset of patients to be electively investigated by
      FNAC, although several may be useful in this regard.

PMID- 17178735
TI  - The moral foundations of health insurance.

PMID- 17178732
TI  - Caspase proteolysis of the integrin beta4 subunit disrupts hemidesmosome
      assembly, promotes apoptosis, and inhibits cell migration.
AB  - Caspases are a conserved family of cell death proteases that cleave intracellular
      substrates at Asp residues to modify their function and promote apoptosis. In
      this report we identify the integrin beta4 subunit as a novel caspase substrate
      using an expression cloning strategy. Together with its alpha6 partner,
      alpha6beta4 integrin anchors epithelial cells to the basement membrane at
      specialized adhesive structures known as hemidesmosomes and plays a critical role
      in diverse epithelial cell functions including cell survival and migration. We
      show that integrin beta4 is cleaved by caspase-3 and -7 at a conserved Asp
      residue (Asp(1109)) in vitro and in epithelial cells undergoing apoptosis,
      resulting in the removal of most of its cytoplasmic tail. Caspase cleavage of
      integrin beta4 produces two products, 1) a carboxyl-terminal product that is
      unstable and rapidly degraded by the proteasome and 2) an amino-terminal cleavage
      product (amino acids 1-1109) that is unable to assemble into mature
      hemidesmosomes. We also demonstrate that caspase cleavage of integrin beta4
      sensitizes epithelial cells to apoptosis and inhibits cell migration. Taken
      together, we have identified a previously unrecognized proteolytic truncation of
      integrin beta4 generated by caspases that disrupts key structural and functional
      properties of epithelial cells and promotes apoptosis.

PMID- 17178737
TI  - Patient knowledge and misconceptions of osteoarthritis assessed by a validated
      self-completed knowledge questionnaire (PKQ-OA).
AB  - OBJECTIVES: To design and validate an osteoarthritis (OA) patient knowledge
      questionnaire (PKQ-OA) and to use it to assess the patients' level of knowledge
      of their disease, treatments and appropriate management techniques. METHODS: The
      PKQ-OA comprises 16 multiple choice questions with 30 correct answers. It was
      developed in two phases and tested for face validity, readability (Flesch Reading
      Index) and understanding, reliability (Kuder-Richardson Formula 20) and
      reproducibility (test/retest). The questionnaire was then used to assess
      knowledge of disease and management of OA in a cohort of 83 patients with
      established disease. RESULTS: The PKQ was found to be fairly easy to read,
      reliable (r = 0.75) and reproducible (r = 0.81; P < 0.01). The overall median
      score for the PKQ-OA was 19 ranging from 8 to 26. There was a highly significant
      association between the scores obtained and the number of years patients had
      spent in formal education, higher scores equating with greater length of
      education (P < 0.005). The majority of patients was knowledgeable about the
      symptoms of OA and exercise, but confused joint protection and energy
      conservation. The most worrying finding was the lack of knowledge regarding
      analgesics and some aspects of non-steroidal anti-inflammatory drug (NSAID)
      therapy. Less than a third of patients knew that analgesics could be taken
      prophylactically and 70% did not know that they should be taken when pain starts
      to build. Among the patients 34% did not know that NSAIDs should be taken with or
      following food. CONCLUSIONS: The PKQ-OA is a readable, reliable and reproducible
      questionnaire. It is quick to complete and score and could be used in out patient
      clinics or GP surgeries to assess knowledge of patients with OA.

PMID- 17178738
TI  - Membrane glucocorticoid receptors (mGCR) on monocytes are up-regulated after
      vaccination.

PMID- 17178739
TI  - A cryopyrin-associated periodic syndrome with joint destruction.
AB  - OBJECTIVE: Describe four generations (11 members) of a family with a cryopyrin
      associated periodic syndrome (CAPS), including joint destruction, associated with
      a CIAS1-gene mutation and good responses to anakinra. METHODS: In addition to
      detailed questioning and physical examination, six family members underwent
      haematological, immunological and biochemical testing. Exon 3 of the CIAS1 gene
      was sequenced in search of a mutation in the 1q44 region. RESULTS: During
      childhood or adolescence, four family members developed different combinations of
      the following CAPS manifestations: deafness (3/4); arthritis (4/4) with joint
      destruction for two of them; nervous (cerebral demyelinization, 2/4), cutaneous
      (livedo and/or urticaria, 3/4) and eye lesions (episcleritis and/or papilloedema,
      4/4); IgA hypergammaglobulinaemia (4/4) and inflammatory syndrome (3/4).
      Sequencing of six family members' CIAS1-gene exon 3 identified a heterozygous
      mutation, c.1043C > T. Pertinently, this CAPS is distinct from chronic infantile
      neurological cutaneous and arthritis syndrome/neonatal onset multisystemic
      inflammatory disease syndrome and Muckle-Wells syndrome (MWS), which also result
      from exon 3 mutations in this gene. Moreover, this family did not have the usual
      neurological manifestations, typical morphological features and frequent
      amyloidosis of MWS. CONCLUSIONS: We describe a previously unreported form of CAPS
      with atypical neurological signs, joint destruction and livedo. This observation
      extends the clinical spectrum associated with CIAS1 mutations. Anakinra, an
      interleukin-1-receptor antagonist, prescribed to two family members, was highly
      effective.

PMID- 17178741
TI  - Get sober; stay sober.

PMID- 17178742
TI  - Manifestations of early brain recovery associated with abstinence from
      alcoholism.
AB  - Chronic alcohol abuse results in morphological, metabolic, and functional brain
      damage which may, to some extent, be reversible with early effects upon
      abstinence. Although morphometric, spectroscopic, and neuropsychological
      indicators of cerebral regeneration have been described previously, the overall
      amount and spatial preference of early brain recovery attained by abstinence and
      its associations with other indicators of regeneration are not well established.
      We investigated global and local brain volume changes in a longitudinal two
      timepoint study with T1-weighted MRI at admission and after short-term (6-7
      weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics.
      Volumetric brain gain was related to metabolic and neuropsychological recovery.
      On admission and after short-term abstinence, structural image evaluation using
      normalization of atrophy (SIENA), its voxelwise statistical extension to multiple
      subjects, proton MR spectroscopy (1H-MRS), and neuropsychological tests were
      applied. Upon short-term sobriety, 1H-MRS levels of cerebellar choline and
      frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically
      detected global brain volume gain amounted to nearly two per cent on average and
      was spatially significant around the superior vermis, perimesencephalic,
      periventricular and frontal brain edges. It correlated positively with the
      percentages of cerebellar and frontomesial choline increase, as detected by 1H
      MRS. Moreover, frontomesial NAA gains were associated with improved performance
      on the d2-test of attention. In 10 age- and gender-matched healthy control
      subjects, no significant brain volume or metabolite changes were observed.
      Although cerebral osmotic regulations may occur initially upon sobriety,
      significant increases of cerebellar choline and frontomesial NAA levels detected
      at stable brain water integrals and creatine concentrations, serum electrolytes
      and red blood cell indices in our patient sample suggest that early brain
      recovery through abstinence does not simply reflect rehydration. Instead, even
      the adult human brain and particularly its white matter seems to possess genuine
      capabilities for regrowth. Our findings emphasize metabolic as well as regionally
      distinct morphological capacities for partial brain recovery from toxic insults
      of chronic alcoholism and substantiate early measurable benefits of therapeutic
      sobriety. Further understanding of the precise mechanisms of this recovery may
      become a valuable model of brain regeneration with relevance for other disorders.

PMID- 17178744
TI  - Recombination in heterozygote inversion carriers.

PMID- 17178743
TI  - Gordon Holmes Lecture: Gordon Holmes and the neurological heritage.
AB  - Sir Gordon Holmes is one of the great figures in the history of twentienth
      century neurology. In him, there came together the traditions of German and
      British neurology which moulded a physiological approach to normal and disordered
      function of the nervous system with a commitment to interpreting clinical
      phenomena in the light of meticulous pathological examination. He, more than any
      other individual, was responsible for the form of the neurological examination as
      it is now performed; and his insights are fundamental to the way that, nowadays,
      we think about vision, somato-sensory function, the spinal cord and the
      cerebellum.

PMID- 17178745
TI  - Psychological distress by type of fertility barrier.
AB  - BACKGROUND: We examined fertility-specific distress (FSD) and general distress by
      type of fertility barrier (FB). METHODS: In a random sample telephone survey, 580
      US women reported their fertility intentions and histories. Six groups of women
      were identified: (i) no FBs, (ii) infertile with intent, (iii) infertile without
      intent, (iv) other fertility problems, (v) miscarriages and (vi) situational
      barriers. Multiple regression analyses were used to compare groups with FBs.
      RESULTS: Sixty-one percent reported FBs and 28% reported an inability to conceive
      for at least 12 months. The infertile with intent group had the highest FSD,
      which was largely explained by (a) self-identification as infertile and (b)
      seeking medical help for fertility. The no FB group had a mean Center for
      Epidemiological Studies Depression scale score above the commonly used cut-off of
      16, although 23% of the women with FBs did score above 16. CONCLUSIONS: FBs are
      common. Self-identification as infertile is the largest source of FSD. More women
      with FBs had elevated general distress than women without FBs; mean general
      distress was below 16 for all FB groups. It may be that, for some women (even
      those with children), FBs can have lasting emotional consequences, but many women
      do heal from the emotional distress that may accompany fertility difficulties.

PMID- 17178746
TI  - Human embryo: a biological definition.
AB  - This paper defines a human embryo from a biological standpoint that takes into
      account emerging technologies in reproductive science. The paper does not
      consider legal, moral, religious or social views. As the definition of a human
      embryo must reflect the multifactorial processes of development, an approach has
      been adopted which combines recognition of observed events with potential for
      further development. This acknowledges that fertilization and development are not
      static processes, and as such embryo status can only be defined by observation of
      specific markers. The following biological definition of 'human embryo' is
      proposed. A human embryo is a discrete entity that has arisen from either: the
      first mitotic division when fertilization of a human oocyte by a human sperm is
      complete or any other process that initiates organized development of a
      biological entity with a human nuclear genome or altered human nuclear genome
      that has the potential to develop up to, or beyond, the stage at which the
      primitive streak appears, and has not yet reached 8 weeks of development since
      the first mitotic division.

PMID- 17178748
TI  - Non-random, individual-specific methylation profiles are present at the sixth
      CTCF binding site in the human H19/IGF2 imprinting control region.

PMID- 17178747
TI  - An enhanced MITOMAP with a global mtDNA mutational phylogeny.
AB  - The MITOMAP (http://www.mitomap.org) data system for the human mitochondrial
      genome has been greatly enhanced by the addition of a navigable mutational
      mitochondrial DNA (mtDNA) phylogenetic tree of approximately 3000 mtDNA coding
      region sequences plus expanded pathogenic mutation tables and a nuclear-mtDNA
      pseudogene (NUMT) data base. The phylogeny reconstructs the entire mutational
      history of the human mtDNA, thus defining the mtDNA haplogroups and
      differentiating ancient from recent mtDNA mutations. Pathogenic mutations are
      classified by both genotype and phenotype, and the NUMT sequences permits
      detection of spurious inclusion of pseudogene variants during mutation analysis.
      These additions position MITOMAP for the implementation of our automated mtDNA
      sequence analysis system, Mitomaster.

PMID- 17178749
TI  - Analysis of the DNA-binding sequence specificity of the archaeal transcriptional
      regulator Ss-LrpB from Sulfolobus solfataricus by systematic mutagenesis and high
      resolution contact probing.
AB  - To determine the sequence specificity of dimeric Ss-LrpB, a high resolution
      contact map was constructed and a saturation mutagenesis conducted on one half of
      the palindromic consensus box. Premodification binding interference indicates
      that Ss-LrpB establishes most of its tightest contacts with a single strand of
      two major groove segments and interacts with the minor groove at the center of
      the box. The requirement for bending is reflected in the preference for an A+T
      rich center and confirmed with C.G and C.I substitutions. The saturation
      mutagenesis indicates that major groove contacts with C.G at position 5 and its
      symmetrical counterpart are most critical for the specificity and strength of the
      interaction. Conservation at the remaining positions improved the binding.
      Hydrogen bonding to the O6 and N7 acceptor atoms of the G5' residue play a major
      role in complex formation. Unlike many other DNA-binding proteins Ss-LrpB does
      not establish hydrophobic interactions with the methyls of thymine residues. The
      binding energies determined from the saturation mutagenesis were used to
      construct a sequence logo, which pin-points the overwhelming importance of C.G at
      position 5. The knowledge of the DNA-binding specificity will constitute a
      precious tool for the search of new physiologically relevant binding sites for Ss
      LrpB in the genome.

PMID- 17178751
TI  - High resolution array-CGH analysis of single cells.
AB  - Heterogeneity in the genome copy number of tissues is of particular importance in
      solid tumor biology. Furthermore, many clinical applications such as pre
      implantation and non-invasive prenatal diagnosis would benefit from the ability
      to characterize individual single cells. As the amount of DNA from single cells
      is so small, several PCR protocols have been developed in an attempt to achieve
      unbiased amplification. Many of these approaches are suitable for subsequent
      cytogenetic analyses using conventional methodologies such as comparative genomic
      hybridization (CGH) to metaphase spreads. However, attempts to harness array-CGH
      for single-cell analysis to provide improved resolution have been disappointing.
      Here we describe a strategy that combines single-cell amplification using
      GenomePlex library technology (GenomePlex) Single Cell Whole Genome Amplification
      Kit, Sigma-Aldrich, UK) and detailed analysis of genomic copy number changes by
      high-resolution array-CGH. We show that single copy changes as small as 8.3 Mb in
      single cells are detected reliably with single cells derived from various tumor
      cell lines as well as patients presenting with trisomy 21 and Prader-Willi
      syndrome. Our results demonstrate the potential of this technology for studies of
      tumor biology and for clinical diagnostics.

PMID- 17178750
TI  - Encoding folding paths of RNA switches.
AB  - RNA co-transcriptional folding has long been suspected to play an active role in
      helping proper native folding of ribozymes and structured regulatory motifs in
      mRNA untranslated regions (UTRs). Yet, the underlying mechanisms and coding
      requirements for efficient co-transcriptional folding remain unclear. Traditional
      approaches have intrinsic limitations to dissect RNA folding paths, as they rely
      on sequence mutations or circular permutations that typically perturb both RNA
      folding paths and equilibrium structures. Here, we show that exploiting sequence
      symmetries instead of mutations can circumvent this problem by essentially
      decoupling folding paths from equilibrium structures of designed RNA sequences.
      Using bistable RNA switches with symmetrical helices conserved under sequence
      reversal, we demonstrate experimentally that native and transiently formed
      helices can guide efficient co-transcriptional folding into either long-lived
      structure of these RNA switches. Their folding path is controlled by the order of
      helix nucleations and subsequent exchanges during transcription, and may also be
      redirected by transient antisense interactions. Hence, transient intra- and inter
      molecular base pair interactions can effectively regulate the folding of nascent
      RNA molecules into different native structures, provided limited coding
      requirements, as discussed from an information theory perspective. This
      constitutive coupling between RNA synthesis and RNA folding regulation may have
      enabled the early emergence of autonomous RNA-based regulation networks.

PMID- 17178752
TI  - GenomeTrafac: a whole genome resource for the detection of transcription factor
      binding site clusters associated with conventional and microRNA encoding genes
      conserved between mouse and human gene orthologs.
AB  - Transcriptional cis-regulatory control regions frequently are found within non
      coding DNA segments conserved across multi-species gene orthologs. Adopting a
      systematic gene-centric pipeline approach, we report here the development of a
      web-accessible database resource--GenomeTraFac (http://genometrafac.cchmc.org)-
      that allows genome-wide detection and characterization of compositionally similar
      cis-clusters that occur in gene orthologs between any two genomes for both
      microRNA genes as well as conventional RNA-encoding genes. Each ortholog gene
      pair can be scanned to visualize overall conserved sequence regions, and within
      these, the relative density of conserved cis-element motif clusters form graph
      peak structures. The results of these analyses can be mined en masse to identify
      most frequently represented cis-motifs in a list of genes. The system also
      provides a method for rapid evaluation and visualization of gene model
      consistency between orthologs, and facilitates consideration of the potential
      impact of sequence variation in conserved non-coding regions to impact complex
      cis-element structures. Using the mouse and human genomes via the NCBI Reference
      Sequence database and the Sanger Institute miRBase, the system demonstrated the
      ability to identify validated transcription factor targets within promoter and
      distal genomic regulatory regions of both conventional and microRNA genes.

PMID- 17178753
TI  - How 'sensible' is the UK Sensible Drinking message? Preliminary findings amongst
      newly matriculated female university students in Scotland.
AB  - BACKGROUND: Current levels and patterns of alcohol drinking continue to cause
      concern, particularly amongst young females. Effective interventions remain
      elusive. The aim of this study was to investigate the levels of knowledge
      relating to UK 'Sensible Drinking' guidelines, definitions of binge drinking and
      attitude to drink labelling initiatives amongst female school leavers enrolling
      at university. METHODS: Non-standardized questionnaires were administered and
      completed by researchers during the process of matriculation (response rate 94%;
      n = 180). RESULTS: The survey revealed that recommended daily guidelines for
      women were not recalled by 54% of participants; 52% could not quote the unit
      content of their favoured alcoholic drink, whereas only 14% reported the use of
      the UK unit system to guide drinking. Personal quantitative definitions of binge
      drinking varied by a factor of 18. CONCLUSION: A rewording of the UK Sensible
      Drinking message to one recognizing the needs of different population groups and
      their particular language of consumption measure is timely.

PMID- 17178754
TI  - Obesity and use of acute hospital services in participants of the Renfrew/Paisley
      study.
AB  - BACKGROUND: Because overweight and obesity are associated with comorbidities,
      increasing levels of overweight and obesity may impact on hospital use. METHODS:
      Body mass index (BMI) in middle age was related to acute hospital use in 7036 men
      and 8327 women from the Renfrew/Paisley prospective cohort study in Scotland.
      Participants in this general population study were examined between 1972 and 1976
      when aged 45-64 years. Acute hospital admissions and bed days per 1000 person
      years were calculated by the World Health Organization BMI categories in the
      follow-up period to 31 March 2004. RESULTS: Underweight and normal weight men had
      lower-than-expected admission rates, and overweight and obese men had higher-than
      expected admission rates. Obese men had higher-than-expected bed day rates. For
      women, there was a U-shaped relationship with admission rate, with normal weight
      women having the lowest admission rate and underweight and obese women having
      similar high rates. Underweight and obese women had higher-than-expected bed day
      rates. CONCLUSIONS: Participants who were obese in midlife had more-than-expected
      acute hospital admissions and in particular more bed days. With levels of obesity
      increasing since this study was started in the 1970s, if these patterns persist,
      there may be increasing demand on health service resources.

PMID- 17178755
TI  - Becoming a health promoting school: evaluating the process of effective
      implementation in Scotland.
AB  - Increasingly, researchers are exploring alternative ways of assessing the impact
      of 'Health Promoting School' (HPS) initiatives, in recognition of the model's
      emphasis on achieving change that is both enduring and far-reaching. However, it
      is still assumed that initiatives will lead to immediate change at the individual
      level. This paper challenges that view and argues that potential markers of
      success associated with process need to be identified earlier as a means of
      supporting schools and teachers. Notwithstanding differences in the way the HPS
      is conceptualized and implemented, four themes are highlighted that have
      relevance beyond any one school or country. These were drawn from a process
      evaluation of a European Network of HPSs Project in Scotland. They highlight the
      ways in which schools were able to successfully adopt HPS principles and the
      conditions that need to be in place for the HPS concept to flourish. Such
      indicators need to be given greater recognition as HPS outcomes if schools are to
      progress beyond the early stages of project implementation.

PMID- 17178756
TI  - A good year for European rheumatology.

PMID- 17178758
TI  - Thrombocytopenia in lupus: baseline C3 as an independent risk factor for relapse.

PMID- 17178757
TI  - Clinical relevance of vertebral fractures.

PMID- 17178759
TI  - Consensus Dutch health assessment questionnaire.

PMID- 17178760
TI  - Inefficacy of infliximab in ankylosing spondylitis is correlated with antibody
      formation.

PMID- 17178761
TI  - Magnetic resonance imaging in patients with rheumatoid arthritis with complete
      remission treated with disease-modifying antirheumatic drugs or anti-tumour
      necrosis factor alpha agents.

PMID- 17178762
TI  - Successful treatment of refractory neuro-Behcet's disease with infliximab: a case
      report to show its efficacy by magnetic resonance imaging, transcranial magnetic
      stimulation and cytokine profile.

PMID- 17178763
TI  - Comparison of different outcome measures for psoriatic arthritis in patients
      treated with infliximab or placebo.

PMID- 17178764
TI  - Interleukin-10 gene promoter polymorphisms and their protein production in
      peritoneal fluid in patients with endometriosis.
AB  - Although associations of interleukin-10 (IL-10) gene promoter polymorphisms and
      their protein production with endometriosis risk have been reported, the
      correlations remain controversial. The objective of this study was to determine
      IL-10 gene promoter polymorphisms at -1082, -819 and -592 sites and their protein
      production in peritoneal fluid (PF) in patients with and without endometriosis.
      IL-10 gene promoter polymorphisms at -1082 site were detected by amplification
      refractory mutation system (ARMS)-PCR and that at -819 and -592 sites was
      genotyped by restriction fragment length polymorphism (RFLP)-PCR. Protein levels
      of IL-10 in PF were measured by enzyme-linked immunosorbent assay (ELISA). There
      were no significant differences in the genotype and allele frequencies of IL-10
      gene promoter polymorphisms at position -1082 between the endometriosis and the
      control groups. However, the frequency of -819 or -592 C alleles was
      significantly increased in patients with endometriosis compared with controls.
      The protein levels of IL-10 in PF were statistically higher in the endometriosis
      group than in the control group. Moreover, the polymorphisms at -1082, -819 and 
      592 sites were associated with protein levels of IL-10 in PF in the endometriosis
      group while in the control group only the polymorphisms at position -1082
      correlated with protein levels. Increased frequency of -819 or -592 C allele and
      increased protein production of IL-10 in PF in patients with endometriosis
      compared with controls and correlations of polymorphisms at -819 and -592 sites
      with protein levels of IL-10 in PF in patients with endometriosis may suggest
      that polymorphisms at -819 and -592 sites and their protein production are
      associated with endometriosis risk.

PMID- 17178765
TI  - Health literacy weakly but consistently predicts primary care patient
      dissatisfaction.
AB  - OBJECTIVES: To study relationships between health literacy and multiple
      satisfaction domains. Health literacy is related to some domains of patient
      satisfaction such as communication and understanding, but little is known about
      relationships of health literacy with other satisfaction domains. Moreover, the
      importance of health literacy in predicting satisfaction compared with other
      patient sociodemographics is underexplored. DESIGN: Cross-sectional survey.
      SETTING: Primary care waiting areas with a Veterans Administration Medical Center
      and a university health system. PARTICIPANTS: One thousand five hundred and
      twenty-eight primary care patients. MAIN OUTCOME MEASURES: A brief demographics
      questionnaire, the Rapid Estimate of Adult Literacy in Medicine, the Veterans
      Affairs ambulatory care patient satisfaction survey, and an adaptation of the
      Charlson Comorbidity Index. RESULTS: In unadjusted regression analyses, lower
      health literacy level was a significant predictor of worse satisfaction in 7 of
      10 domains (P < 0.01). When adjusting for patient sociodemographics, predicted
      relationships remained significant in six of the seven domains (P < 0.05), with
      each unit change in the 4-stage literacy classification associated with a 3-6
      point decrease in dissatisfaction scores (0-100 scale). Health literacy did not
      predict overall dissatisfaction (P = 0.55). CONCLUSIONS: These results suggest
      that health literacy, as assessed through a pronunciation exercise that is
      closely related to more comprehensive measures of literacy, has a consistent,
      albeit weak relationship with patient satisfaction. Future work is needed to
      clarify if patients with lower literacy are really receiving different care than
      those with higher literacy and to pinpoint the sources of their more negative
      responses.

PMID- 17178766
TI  - Prognosis assessment in stroke patients at discharge from hospital.
AB  - BACKGROUND: accurate prognostic assessments of need of help, health and dwelling
      situation in stroke patients are important for patient management,
      rehabilitation, discharge planning, and for providing reliable information to
      patients and their relatives. OBJECTIVE: to analyse factors affecting the
      accuracy of discharge prognosis assessments. DESIGN: prospective study of stroke
      patients discharged from hospital. SETTING: two cities in central Sweden.
      SUBJECTS: three hundred and ninety stroke patients, 65 years or older, living in
      their own homes and having no dementia diagnosis prior to hospital admission.
      METHODS: at discharge, physicians, nurses, occupational therapists and
      physiotherapists in the Departments of Internal Medicine and Geriatrics were
      asked to make an individual prognosis assessment regarding patients' need for
      help, health and dwelling situation at 3 and 12 months after admission to
      hospital. RESULTS: the prognosis assessments were on average accurate in 68.4% (3
      months) and 61.5% (12 months), far better than chance (33.3%). There were no
      significant differences between staff categories. The accuracy was influenced by
      a number of patient linked factors, such as activity degree, household situation
      before admission, and Mini Mental State Examination level and need of help
      measured 1 week after discharge, and ranged from 22 to 89%, depending on factor
      combinations. CONCLUSIONS: prognosis assessments based on clinical judgement were
      on average quite accurate but the accuracy varied markedly with patient linked
      factors. Feedback of outcome might be one way to further improve the accuracy of
      prognosis assessment.

PMID- 17178767
TI  - Involvement of CYP2A6 in the formation of a novel metabolite, 3
      hydroxypilocarpine, from pilocarpine in human liver microsomes.
AB  - Pilocarpine is a cholinergic agonist that is metabolized to pilocarpic acid by
      serum esterase. In this study, we discovered a novel metabolite in human urine
      after the oral administration of pilocarpine hydrochloride, and we investigated
      the metabolic enzyme responsible for the metabolite formation. The structure of
      the metabolite was identified as 3-hydroxypilocarpine by liquid chromatography
      tandem mass spectrometry and NMR analyses and by comparing to the authentic
      metabolite. To clarify the human cytochrome P450 (P450) responsible for the
      metabolite formation, in vitro experiments using P450 isoform-selective
      inhibitors, cDNA-expressed human P450s (Supersomes; CYP1A2, -2A6, -2B6, -2C9, 
      2C19, -2D6, -2E1, and -3A4), and liver microsomes from different donors were
      conducted. The formation of 3-hydroxypilocarpine in human liver microsomes was
      strongly inhibited (>90%) by 200 microM coumarin. Other selective inhibitors of
      CYP1A2 (furafylline and alpha-naphthoflavone), CYP2C9 (sulfaphenazole), CYP2C19
      [(S)-mephenytoin], CYP2E1 (4-methylpyrazole), CYP2D6 (quinidine), and CYP3A4
      (troleandomycin) had a weak inhibitory effect (<20%) on the formation. The
      highest formation activity was expressed by recombinant CYP2A6. The K(m) value
      for recombinant CYP2A6 was 3.1 microM, and this value is comparable with that of
      human liver microsomes (1.5 microM). The pilocarpine 3-hydroxylation activity was
      correlated with coumarin 7-hydroxylation activity in 16 human liver microsomes (r
      = 0.98). These data indicated that CYP2A6 is the main enzyme responsible for the
      3-hydroxylation of pilocarpine. In conclusion, we identified a novel metabolite
      of pilocarpine, 3-hydroxypilocarpine, and we clarified the involvement of CYP2A6
      in the formation of this molecule in human liver microsomes.

PMID- 17178768
TI  - Characterization of the hepatic disposition of lanoteplase, a rationally designed
      variant of tissue plasminogen activator in rodents.
AB  - Lanoteplase is a recombinant mutant of tissue-type plasminogen activator (t-PA)
      that was developed with an aim to overcome the drawback of rapid systemic
      elimination of t-PA. In this study, we examined the disposition profile of
      lanoteplase in vivo and the kinetics of receptor-mediated endocytosis (RME) of
      this recombinant t-PA in vitro to kinetically characterize the mechanism(s)
      underlying its tissue distribution and elimination. Integration plot analysis of
      the initial-phase tissue distribution in rats revealed a much lower uptake
      clearance (CL(uptake)) of lanoteplase in the liver than that of t-PA. Rate
      constants for cell surface binding, internalization, and degradation of
      lanoteplase were also lower than those for t-PA in primary cultured rat
      hepatocytes. These results suggest that the improved stability of lanoteplase in
      vivo could be accounted for by the delay in the RME of this recombinant protein.
      The CL(uptake) in the liver decreased with coadministration of lactoferrin, a
      ligand for the low-density lipoprotein receptor-related protein (LRP) and the
      asialoglycoprotein (ASGP) receptors in normal mice, and in lrpap1((-/-)) mice,
      which have a hereditary deficiency of LRP; In contrast, CL(uptake) was not
      affected by mannose, whereas that of t-PA decreased with both ligands and in the
      lrpap1((-/-)) mice. Thus, the hepatic disposition of lanoteplase seems to be
      mediated by common specific receptors for t-PA, including LRP and the ASGP
      receptors, whereas the mannose receptor seems to be only minimally involved in
      the disposition of lanoteplase.

PMID- 17178769
TI  - Pharmacokinetics and pharmacodynamics of alfentanil in P-glycoprotein-competent
      and P-glycoprotein-deficient mice: P-glycoprotein efflux alters alfentanil brain
      disposition and antinociception.
AB  - Previous studies have indicated that P-glycoprotein (P-gp) attenuates the central
      nervous system penetration and central activity of some opioids. The impact of P
      gp-mediated efflux on the disposition and efficacy of the synthetic opioid
      alfentanil currently is unknown. In this study, P-gp-competent [mdr1a(+/+)] and P
      gp-deficient [mdr1a(-/-)] mice were used to investigate the impact of P-gp
      mediated efflux on the systemic pharmacokinetics, brain disposition, and central
      activity of alfentanil. Equipotent doses of alfentanil were administered to
      mdr1a(+/+) and mdr1a(-/-) mice (0.2 and 0.067 mg/kg, respectively), and the time
      course of brain and serum concentrations as well as antinociception were
      determined. A pharmacokinetic-pharmacodynamic (PK-PD) model was fit to the data
      and used to assess the impact of P-gp on parameters associated with alfentanil
      disposition and action. The mdr1a(+/+) mice were less sensitive to alfentanil
      than mdr1a(-/-) mice, requiring a 3-fold higher dose to produce similar
      antinociception. PK-PD modeling revealed no differences in alfentanil systemic
      pharmacokinetics between P-gp expressers and nonexpressers. However, the steady
      state brain-to-serum concentration ratio (K(p,brain,ss)) was approximately 3-fold
      lower in mdr1a(+/+) mice compared with mdr1a(-/-) mice (0.19 +/- 0.01 versus 0.54
      +/- 0.04, respectively). Consistent with the approximately 3-fold lower
      K(p,brain,ss), the antinociception versus serum concentration relationship in
      mdr1a(+/+) mice was shifted approximately 3-fold rightward compared with mdr1a(-/
      ) mice. However, there was no difference in the antinociception versus brain
      concentration relationship, or in the brain tissue EC(50) (11 +/- 1.8 versus 9.2
      +/- 1.7 ng/g), between mdr1a(+/+) and mdr1a(-/-) mice. These results indicate
      that alfentanil is an in vivo P-gp substrate and are consistent with the
      hypothesis that P-gp-mediated efflux attenuates antinociception by reducing
      alfentanil K(p,brain,ss).

PMID- 17178770
TI  - Helices F-G are important for the substrate specificities of CYP3A7.
AB  - CYP3A7 is a member of the human CYP3A family and a major form of P450 expressed
      in human fetal livers. Although CYP3A7 shares nearly 90% base sequence with
      CYP3A4, CYP3A7 shows striking functional differences in the catalytic preference
      for several substrates, such as dehydroepiandrosterone (DHEA) or
      dehydroepiandrosterone 3-sulfate (DHEA-3S). First, to clarify the reason for the
      differences between CYP3A7 and CYP3A4, a homology model of CYP3A7 was constructed
      using the CYP3A4 crystal structure. Because these two structures were similar,
      four kinds of chimeric enzymes were constructed to determine which sequences are
      important for exhibiting the characteristics of CYP3A7. The results of kinetic
      analysis of DHEA and DHEA-3S 16alpha-hydroxylations by CYP3A7, CYP3A4, and CYP3A
      chimeras suggested that the amino acid residues from Leu(210) to Glu(279) were
      important to express the specificity for substrates as CYP3A7. This region was on
      the F and G helices of the modeled CYP3A7. Furthermore, to assess which amino
      acid in this sequence is important for the substrate specificity of CYP3A7, a one
      point mutation of CYP3A7 to CYP3A4 was made by site-directed mutagenesis. The
      mutants of K224T and K244E had lost DHEA and DHEA-3S 16alpha-hydroxylation
      activities. The mutants also greatly decreased the metabolism of testosterone,
      erythromycin, nevirapine, and triazolam relative to those activities of CYP3A7
      wild-type enzyme. From these results, it is expected that CYP3A7 can recognize
      specific substrates using the lysines in F-G loops.

PMID- 17178771
TI  - CYP2A13 metabolizes the substrates of human CYP1A2, phenacetin, and theophylline.
AB  - Human cytochrome CYP2A13 shows overlapping substrate specificity with CYP2A6,
      catalyzing the metabolism of coumarin, nicotine, cotinine, and 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone. Recently, it was found that CYP2A13
      could catalyze the metabolic activations of 4-aminobiphenyl and aflatoxin B(1),
      which are known to be catalyzed by human CYP1A2. In the present study, we
      investigated the substrate specificity of CYP2A13. It was shown that CYP2A13
      could catalyze ethoxyresorufin O-deethylation, methoxyresorufin O-demethylation,
      and phenacetin O-deethylation, which are used as marker activities for human
      CYP1A2. Although the intrinsic clearances (V(max)/K(m)) of the two former
      reactions by CYP2A13 were much lower than that of CYP1A2, the value of the last
      reaction by CYP2A13 was 2-fold higher than that of CYP1A2. Of particular interest
      was that CYP2A13 has higher affinity toward phenacetin than CYP1A2. In contrast,
      CYP2A6 hardly catalyzed these reactions, although the amino acid identity with
      CYP2A13 is as high as 93.5%. Furthermore, we found that CYP2A13 can catalyze
      theophylline 8-hydroxylation and 3-demethylation, which are known to be mainly
      catalyzed by human CYP1A2, although the intrinsic clearances were approximately
      one-tenth that of CYP1A2. CYP2A13 would not contribute to the systemic clearance
      of these drugs because CYP2A13 is hardly expressed in human liver. However, it
      may play a role in metabolism in local tissues such as lung or trachea. In
      conclusion, the results of the present study could extend our understanding of
      the substrate specificity of CYP2A13.

PMID- 17178772
TI  - Hydrodilatation (distension arthrography): a long-term clinical outcome series.
AB  - OBJECTIVES: To describe and compare the medium to long-term effectiveness of
      hydrodilatation and post-hydrodilatation physiotherapy in patients with primary
      and secondary glenohumeral joint contracture associated with rotator cuff
      pathology. METHODS: Patients with primary and secondary glenohumeral contractures
      associated with rotator cuff pathology were recruited into a 2-year study. They
      all underwent hydrodilatation, followed by a structured physiotherapy programme.
      Patients were assessed at baseline, 3 days, 1 week, 3 months, 1 year and 2 years
      after hydrodilatation with primary outcome measures (Shoulder Pain and Disability
      Index, Shoulder Disability Index and percentage rating of "normal" function; SD%)
      and secondary outcome measures (range of shoulder abduction, external rotation
      and hand behind back). Comparisons in recovery were made between the primary and
      secondary glenohumeral contracture groups at all timeframes and for all outcome
      measures. RESULTS: A total of 53 patients (23 with primary and 30 with secondary
      glenohumeral contractures) were recruited into the study. At the 2-year follow
      up, 12 patients dropped out from the study. At baseline, the two contracture
      groups were similar with respect to their demographic and physical
      characteristics. The two groups of patients recovered in a similar fashion over
      the 2-year follow-up period. A significant improvement was observed in all
      outcomes measures over this period (p<0.01), so that both function and range of
      movement increased. The rate of improvement was dependent on the outcome measure
      that was used. CONCLUSIONS: Hydrodilatation and physiotherapy increase shoulder
      motion in individuals with primary and secondary glenohumeral joint contracture
      associated with rotator cuff pathology. This benefit continues to improve or is
      maintained in the long term, up to 2 years after hydrodilatation.

PMID- 17178773
TI  - Trends in physical activity and sedentary behaviour in adolescence: ethnic and
      socioeconomic differences.
AB  - OBJECTIVE: To assess developmental trends in physical activity and sedentary
      behaviour in British adolescents in relation to sex, ethnicity and socioeconomic
      status (SES). DESIGN: A 5-year longitudinal study of a diverse cohort of students
      aged 11-12 years at baseline in 1999. SETTING: 36 London schools sampled using a
      stratified random sampling procedure. PARTICIPANTS: A total of 5863 students
      categorised as white, black or Asian, and stratified for SES using the Townsend
      Index. MAIN OUTCOME MEASURES: Number of days per week of vigorous activity
      leading to sweating and breathing hard. Hours of sedentary behaviour, including
      watching television and playing video games. Data were analysed using multilevel,
      linear, mixed models. RESULTS: Marked reductions in physical activity and
      increases in sedentary behaviour were noticed between ages 11-12 and 15-16 years.
      Boys were more active than girls, and the decline in physical activity was
      greater in girls (46% reduction) than in boys (23%). Asian students were less
      active than whites, and this was also true of black girls but not boys. Black
      students were more sedentary than white students. Levels of sedentary behaviour
      were greater in respondents from lower SES. Most differences between ethnic and
      SES groups were present at age 11 years, and did not evolve over the teenage
      years. CONCLUSIONS: Physical activity declines and sedentary behaviour becomes
      more common during adolescence. Ethnic and SES differences are observed in
      physical activity and sedentary behaviour in British youth that anticipate adult
      variations in adiposity and cardiovascular disease risk. These are largely
      established by age 11-12 years, so reversing these patterns requires earlier
      intervention.

PMID- 17178775
TI  - Validation of a field test to determine the maximal aerobic power in triathletes
      and endurance cyclists.
AB  - OBJECTIVE: To validate a field test to assess the maximal and submaximal exercise
      aerobic adaptation under specific conditions, for endurance modality cyclists and
      triathletes. METHODS: 30 male and 4 female endurance modality cyclists and
      triathletes, with heterogeneous performance levels, performed three incremental
      tests: one in the laboratory and two in the field. Assessment of the validity of
      the field protocol was carried out by the Student's t test, intraclass
      correlation coefficient (ICC) and coefficient of variation (CV) of the maximal
      variables (maximal aerobic speed (MAS), maximal aerobic power (MAP), maximal
      heart rate (HR(max)), maximal blood lactate concentration ([La(-)](max)) and
      maximal oxygen uptake (VO(2max))) and submaximal variables (heart rate, HR)
      measured in each one of the tests. The errors in measurement were calculated. The
      repeatability of the field tests was assessed by means of the test-retest of the
      two field tests, and the validity by means of the test-retest of the laboratory
      test with respect to the mean of the two field tests. RESULTS: No significant
      differences were found between the two field tests for any of the variables
      studied, but differences did exist for some variables between the laboratory
      tests with respect to the field tests (MAP, [La(-)](max), humidity (H),
      barometric pressure (Pb) and some characteristics of the protocols). The ICC of
      all the variables was high and the CV for the MAP was small. Furthermore, the
      measurement errors were small and therefore, assumable. CONCLUSIONS: The
      incremental protocol of the proposed field test turned out to be valid to assess
      the maximal and submaximal aerobic adaptation.

PMID- 17178774
TI  - The additional value of a night splint to eccentric exercises in chronic
      midportion Achilles tendinopathy: a randomised controlled trial.
AB  - AIM: To assess whether the use of a night splint is of added benefit on
      functional outcome in treating chronic midportion Achilles tendinopathy. METHODS:
      This was a single-blind, prospective, single centre, randomised controlled trial
      set in the Sports Medical Department, The Hague Medical Centre, The Netherlands.
      Inclusion criteria were: age 18-70 years, active participation in sports, and
      tendon pain localised at 2-7 cm from distal insertion. Exclusion criteria were:
      insertional disorders, partial or complete ruptures, or systemic illness. 70
      tendons were included and randomised into one of two treatment groups: eccentric
      exercises with a night splint (night splint group, n = 36) or eccentric exercises
      only (eccentric group, n = 34). INTERVENTIONS: Both groups completed a 12-week
      heavy-load eccentric training programme. One group received a night splint in
      addition to eccentric exercises. At baseline and follow-up at 12 weeks, patient
      satisfaction, Victorian Institute of Sport Assessment-Achilles questionnaire
      (VISA-A) score and reported compliance were recorded by a single-blind trained
      researcher who was blinded to the treatment. RESULTS: After 12 weeks, patient
      satisfaction in the eccentric group was 63% compared with 48% in the night splint
      group. The VISA-A score significantly improved in both groups; in the eccentric
      group from 50.1 to 68.8 (p = 0.001) and in the night splint group from 49.4 to
      67.0 (p<0.001). There was no significant difference between the two groups in
      VISA-A score (p = 0.815) and patient satisfaction (p = 0.261). CONCLUSION: A
      night splint is not beneficial in addition to eccentric exercises in the
      treatment of chronic midportion Achilles tendinopathy.

PMID- 17178776
TI  - Higher plantar pressure on the medial side in four soccer-related movements.
AB  - OBJECTIVE: To measure the plantar pressure in four soccer-related movements in 15
      male soccer players (mean (SD) age 20.9 (1.3) years, height 173 (4) cm, weight
      61.7 (3.6) kg). DESIGN: To record plantar pressure distribution, the players wore
      soccer boots with 12 circular studs and with an insole pressure recorder device
      equipped with 99 sensors. Plantar pressure was recorded in five successful trials
      in each of the four soccer-related movements: running, sideward cutting, 45
      degrees cutting and landing from a vertical jump. Each footprint was divided into
      10 recorded areas for analysis. RESULTS: Compared with running at 3.3 m/s,
      maximal speed sideward cutting and 45 degrees cutting induced higher peak
      pressure (p<0.05) under the second toe, medial forefoot, medial arch and medial
      heel. The peak pressure of the maximal jump landing was lower under the medial
      forefoot and lateral forefoot as compared with running (p<0.05). The pressure
      time integral showed that sideward cutting and 45 degrees cutting induced higher
      pressures (p<0.05) than running for all recorded areas, except for the lateral
      forefoot and the lateral arch. In all the four soccer-related movements, a higher
      pressure was found on the medial side of the plantar surface as compared with the
      lateral side. CONCLUSIONS: These data suggest that the medial side of the plantar
      surface may be more prone to injuries, and that foot orthosis adoption, improved
      soccer boot design and specific muscle training could be considered to reduce
      pressure and the subsequent risk of injury.

PMID- 17178777
TI  - Left ventricular early myocardial dysfunction after chronic misuse of anabolic
      androgenic steroids: a Doppler myocardial and strain imaging analysis.
AB  - BACKGROUND: Anabolic androgenic steroids (AAS) are sometimes used by power
      athletes to improve performance by increasing muscle mass and strength. Recent
      bioptical data have shown that in athletes under the pharmacological effects of
      AAS, a focal increase in myocardial collagen content might occur as a repair
      mechanism against myocardial damage. OBJECTIVE: To investigate the potential
      underlying left ventricular myocardial dysfunction after chronic misuse of AAS in
      athletes by use of Doppler myocardial imaging (DMI) and strain rate imaging
      (SRI). METHODS: Standard Doppler echocardiography, DMI, SRI and ECG treadmill
      test were undertaken by 45 bodybuilders, including 20 athletes misusing AAS for
      at least 5 years (users), by 25 anabolic-free bodybuilders (non-users) and by 25
      age-matched healthy sedentary controls, all men. The mean (SD) number of weeks of
      AAS use per year was 31.3 (6.4) in users, compared with 8.9 (3.8) years in non
      users, and the mean weekly dosage of AAS was 525.4 (90.7) mg. RESULTS: The groups
      were matched for age. Systolic blood pressure was higher in athletes (145 (9) vs
      130 (5) mm Hg) than in controls. Left ventricular mass index did not
      significantly differ between the two groups of athletes. In particular, both
      users and non-users showed increased wall thickness and relative wall thickness
      compared with controls, whereas left ventricular ejection fraction, left
      ventricular end-diastolic diameter and transmitral Doppler indexes were
      comparable for the three groups. Colour DMI analysis showed significantly lower
      myocardial early: myocardial atrial diastolic wave ratios in users at the level
      of the basal interventricular septum (IVS) and left ventricular lateral wall
      (p<0.01), in comparison with both non-users and controls. In addition, in users,
      peak systolic left ventricular strain rate and strain were both reduced in the
      middle IVS (both p<0.001) and in the left ventricular lateral free wall (both
      p<0.01). By stepwise forward multivariate analyses, the sum of the left
      ventricular wall thickness (beta coefficient = -0.32, p<0.01), the number of
      weeks of AAS use per year (beta = -0.42, p<0.001) and the weekly dosage of AAS
      (beta = -0.48, p<0.001) were the only independent determinants of middle IVS
      strain rate. In addition, impaired left ventricular strain in users was
      associated with a reduced performance during physical effort (p<0.001).
      CONCLUSIONS: Several years after chronic misuse of AAS, power athletes show a
      subclinical impairment of both systolic and diastolic myocardial function,
      strongly associated with mean dosage and duration of AAS use. The combined use of
      DMI and SRI may therefore be useful for the early identification of patients with
      more diffused cardiac involvement, and eventually for investigation of the
      reversibility of such myocardial effects after discontinuation of the drug.

PMID- 17178778
TI  - The ingestible telemetric body core temperature sensor: a review of validity and
      exercise applications.
AB  - An ingestible telemetric temperature sensor for measuring body core temperature
      (Tc) was first described 45 years ago, although the method has only recently
      gained widespread use for exercise applications. This review aims to (1) use
      Bland and Altman's limits of agreement (LoA) method as a basis for quantitatively
      reviewing the agreement between intestinal sensor temperature (Tintestinal),
      oesophageal temperature (Toesophageal) and rectal temperature (Trectal) across
      numerous previously published validation studies; (2) review factors that may
      affect agreement; and (3) review the application of this technology in field
      based exercise studies. The agreement between Tintestinal and Toesophageal is
      suggested to meet our delimitation for an acceptable level of agreement (ie,
      systematic bias <0.1 degrees C and 95% LoA within +/-0.4 degrees C). The
      agreement between Tintestinal and Trectal shows a significant systematic bias
      >0.1 degrees C, although the 95% LoA is acceptable. Tintestinal responds less
      rapidly than Toesophageal at the start or cessation of exercise or to a change in
      exercise intensity, but more rapidly than Trectal. When using this technology,
      care should be taken to ensure adequate control over sensor calibration and data
      correction, timing of ingestion and electromagnetic interference. The ingestible
      sensor has been applied successfully in numerous sport and occupational
      applications such as the continuous measurement of Tc in deep sea saturation
      divers, distance runners and soldiers undertaking sustained military training
      exercises. It is concluded that the ingestible telemetric temperature sensor
      represents a valid index of Tc and shows excellent utility for ambulatory field
      based applications.

PMID- 17178779
TI  - Expression of the Yersinia enterocolitica pYV-encoded type III secretion system
      is modulated by lipopolysaccharide O-antigen status.
AB  - We show that the expression of a Yersinia enterocolitica O:8 pYV-encoded type III
      secretion system was altered in a rough mutant (YeO8-R) due to elevated levels of
      FlhDC. H-NS might underlie flhDC upregulation in YeO8-R, and the data suggest a
      relationship between the absence of O antigen and the expression of H-NS.

PMID- 17178780
TI  - The Psa fimbriae of Yersinia pestis interact with phosphatidylcholine on alveolar
      epithelial cells and pulmonary surfactant.
AB  - The pH 6 antigen (Psa) of Yersinia pestis consists of fimbriae with adhesive
      properties of potential importance for the pathogenesis of plague, including
      pneumonic plague. The Psa fimbriae mediate bacterial binding to human alveolar
      epithelial cells. The Psa fimbriae bound mostly to one component present in the
      total lipid extract from type II alveolar epithelial cells of the cell line A549
      separated by thin-layer chromatography (TLC). The Psa receptor was identified as
      phosphatidylcholine (PC) by TLC using alkali treatment, molybdenum blue staining,
      and Psa overlays. The Psa fimbriae bound to PC in a dose-dependent manner, and
      binding was inhibited by phosphorylcholine (ChoP) and choline. Binding inhibition
      was dose dependent, although only high concentrations of ChoP completely blocked
      Psa binding to PC. In contrast, less than 1 muM of a ChoP-polylysine polymer
      inhibited specifically the adhesion of Psa-fimbriated Escherichia coli to PC, and
      type I (WI-26 VA4) and type II alveolar epithelial cells. These results indicated
      that the homopolymeric Psa fimbriae are multimeric adhesins. Psa also bound to
      pulmonary surfactant, which covers the alveolar surface as a product of type II
      alveolar epithelial cells and includes PC as the major component. The observed
      dose-dependent interaction of Psa with pulmonary surfactant was blocked by ChoP.
      Interestingly, surfactant did not inhibit Psa-mediated bacterial binding to
      alveolar cells, suggesting that both surfactant and cell membrane PC retain Psa
      fimbriated bacteria on the alveolar surface. Altogether, the results indicate
      that Psa uses the ChoP moiety of PC as a receptor to mediate bacterial binding to
      pulmonary surfactant and alveolar epithelial cells.

PMID- 17178781
TI  - Coactivating signals for the hepatic lymphocyte gamma interferon response to
      Francisella tularensis.
AB  - The facultative intracellular bacterium Francisella tularensis is capable of
      causing systemic infections in various hosts, including mice and humans. The
      liver is a major secondary site of F. tularensis infection, but hepatic immune
      responses to the pathogen remain poorly defined. Immune protection against the
      pathogen is thought to depend on the cytokine gamma interferon (IFN-gamma), but
      the cellular basis for this response has not been characterized. Here we report
      that natural killer cells from the livers of naive uninfected mice produced IFN
      gamma when challenged with live bacteria in vitro and that the responses were
      greatly increased by coactivation of the cells with either recombinant
      interleukin-12 (IL-12) or IL-18. Moreover, the two cytokines had strong
      synergistic effects on IFN-gamma induction. Neutralizing antibodies to either IL
      12 or IL-18 inhibited IFN-gamma production in vitro, and mice deficient in the
      p35 subunit of IL-12 failed to show IFN-gamma responses to bacterial challenge
      either in vitro or in vivo. Clinical isolates of highly virulent type A
      Francisella tularensis subsp. tularensis organisms were comparable to the live
      attenuated vaccine strain of Francisella tularensis subsp. holarctica in their
      ability to induce IL-12 and IFN-gamma expression. These findings demonstrate that
      cells capable of mounting IFN-gamma responses to F. tularensis are resident
      within the livers of uninfected mice and depend on coactivation by IL-12 and IL
      18 for optimum responses.

PMID- 17178782
TI  - Chlamydia muridarum infection elicits a beta interferon response in murine
      oviduct epithelial cells dependent on interferon regulatory factor 3 and TRIF.
AB  - Chlamydia trachomatis is the most common sexually transmitted bacterial infection
      in the United States. Utilizing cloned murine oviduct epithelial cell lines, we
      previously identified Toll-like receptor 2 (TLR2) as the principal epithelial
      pattern recognition receptor (PRR) for infection-triggered release of the acute
      inflammatory cytokines interleukin-6 and granulocyte-macrophage colony
      stimulating factor. The infected oviduct epithelial cell lines also secreted the
      immunomodulatory cytokine beta interferon (IFN-beta) in a largely MyD88
      independent manner. Although TLR3 was the only IFN-beta production-capable TLR
      expressed by the oviduct cell lines, we were not able to determine whether TLR3
      was responsible for IFN-beta production because the epithelial cells were
      unresponsive to the TLR3 ligand poly(I-C), and small interfering RNA (siRNA)
      techniques were ineffective at knocking down TLR3 expression. To further
      investigate the potential role of TLR3 in the infected epithelial cell secretion
      of IFN-beta, we examined the roles of its downstream signaling molecules TRIF and
      IFN regulatory factor 3 (IRF-3) using a dominant-negative TRIF molecule and siRNA
      specific for TRIF and IRF-3. Antagonism of either IRF-3 or TRIF signaling
      significantly decreased IFN-beta production. These data implicate TLR3, or an
      unknown PRR utilizing TRIF, as the source of IFN-beta production by Chlamydia
      infected oviduct epithelial cells.

PMID- 17178784
TI  - Cellular pyrin domain-only protein 2 is a candidate regulator of inflammasome
      activation.
AB  - Pyrin domain (PYD) proteins have recently emerged as important signaling
      molecules involved in the development of innate immunity against intracellular
      pathogens through activation of inflammatory mediator pathways. ASC is the
      central adaptor protein, which links pathogen recognition by PYD-containing
      pathogen recognition receptors, known as PYD-Nod-like receptors (NLR), PAN,
      PYPAF, NALP, Nod, and Caterpiller proteins, to the activation of downstream
      effectors, including activation of caspase-1 and NF-kappaB. Activation of these
      effectors occurs when specific protein complexes, known as inflammasomes, are
      formed. PYD signal transduction leads to inflammasome assembly and activation of
      specific effector proteins. It is modulated by a cellular PYD-only protein
      (cPOP1), which binds to ASC and interferes with the recruitment of ASC to
      activated PYD-NLRs. Here we describe the identification and characterization of a
      second cellular POP (cPOP2), which shows highest homology to the PYD of PAN1.
      cPOP2 binds to ASC and PAN1, thereby blocking formation of cryopyrin and PAN1
      containing inflammasomes, activation of caspase-1, and subsequent processing and
      secretion of bioactive interleukin-1beta. Existence of a second cPOP provides
      additional insights into inflammasome formation and suggests that POPs might be a
      common regulatory mechanism to "fine-tune" the activity of specific PYD-NLR
      family protein-containing inflammasomes.

PMID- 17178783
TI  - Virally activated CD8 T cells home to Mycobacterium bovis BCG-induced granulomas
      but enhance antimycobacterial protection only in immunodeficient mice.
AB  - The effect of secondary infections on CD4 T-cell-regulated chronic granulomatous
      inflammation is not well understood. Here, we have investigated the effect of an
      acute viral infection on the cellular composition and bacterial protection in
      Mycobacterium bovis strain bacille Calmette-Guerin (BCG)-induced granulomas using
      an immunocompetent and a partially immunodeficient murine model. Acute
      lymphocytic choriomeningitis virus (LCMV) coinfection of C57BL/6 mice led to
      substantial accumulation of gamma interferon (IFN-gamma)-producing LCMV-specific
      T cells in liver granulomas and increased local IFN-gamma. Despite traffic of
      activated T cells that resulted in a CD8 T-cell-dominated granuloma, the BCG
      liver organ load was unaltered from control levels. In OT-1 T-cell-receptor (TCR)
      transgenic mice, ovalbumin (OVA) immunization or LCMV coinfection of BCG-infected
      mice induced CD8 T-cell-dominated granulomas containing large numbers of non-BCG
      specific activated T cells. The higher baseline BCG organ load in this CD8 TCR
      transgenic animal allowed us to demonstrate that OVA immunization and LCMV
      coinfection increased anti-BCG protection. The bacterial load remained
      substantially higher than in mice with a more complete TCR repertoire. Overall,
      the present study suggests that peripherally activated CD8 T cells can be
      recruited to chronic inflammatory sites, but their contribution to protective
      immunity is limited to conditions of underlying immunodeficiency.

PMID- 17178785
TI  - Pseudolipasin A is a specific inhibitor for phospholipase A2 activity of
      Pseudomonas aeruginosa cytotoxin ExoU.
AB  - A number of bacterial pathogens utilize the type III secretion pathway to deliver
      effector proteins directly into the host cell cytoplasm. Certain strains of
      Pseudomonas aeruginosa associated with acute infections express a potent
      cytotoxin, exoenzyme U (ExoU), that is delivered via the type III secretion
      pathway directly into contacting host cells. Once inside the mammalian cell, ExoU
      rapidly lyses the intoxicated cells via its phospholipase A(2) (PLA(2)) activity.
      A high-throughput cell-based assay was developed to screen libraries of compounds
      for those capable of protecting cells against the cytotoxic effects of ExoU. A
      number of compounds were identified in this screen, including one group that
      blocks the intracellular activity of ExoU. In addition, these compounds
      specifically inhibited the PLA(2) activity of ExoU in vitro, whereas eukaryotic
      secreted PLA(2) and cytosolic PLA(2) were not inhibited. This novel inhibitor of
      ExoU-specific PLA(2) activity, named pseudolipasin A, may provide a new lead for
      virulence factor-based therapeutic design.

PMID- 17178787
TI  - Selection for simple major surface protein 2 variants during Anaplasma marginale
      transmission to immunologically naive animals.
AB  - Anaplasma marginale, a rickettsial pathogen, evades clearance in the animal host
      by antigenic variation. Under immune selection, A. marginale expresses complex
      major surface protein 2 mosaics, derived from multiple donor sequences. However,
      these mosaics have a selective advantage only in the presence of adaptive
      immunity and are rapidly replaced by simple variants following transmission.

PMID- 17178786
TI  - Aspergillus fumigatus does not require fatty acid metabolism via isocitrate lyase
      for development of invasive aspergillosis.
AB  - Aspergillus fumigatus is the most prevalent airborne filamentous fungus causing
      invasive aspergillosis in immunocompromised individuals. Only a limited number of
      determinants directly associated with virulence are known, and the metabolic
      requirements of the fungus to grow inside a host have not yet been investigated.
      Previous studies on pathogenic microorganisms, i.e., the bacterium Mycobacterium
      tuberculosis and the yeast Candida albicans, have revealed an essential role for
      isocitrate lyase in pathogenicity. In this study, we generated an isocitrate
      lyase deletion strain to test whether this strain shows attenuation in virulence.
      Results have revealed that isocitrate lyase from A. fumigatus is not required for
      the development of invasive aspergillosis. In a murine model of invasive
      aspergillosis, the wild-type strain, an isocitrate lyase deletion strain, and a
      complemented mutant strain were similarly effective in killing mice. Moreover,
      thin sections demonstrated invasive growth of all strains. Additionally, thin
      sections of lung tissue from patients with invasive aspergillosis stained with
      anti-isocitrate lyase antibodies remained negative. From these results, we cannot
      exclude the use of lipids or fatty acids as a carbon source for A. fumigatus
      during invasive growth. Nevertheless, test results do imply that the glyoxylate
      cycle from A. fumigatus is not required for the anaplerotic synthesis of
      oxaloacetate under infectious conditions. Therefore, an antifungal drug
      inhibiting fungal isocitrate lyases, postulated to act against Candida
      infections, is assumed to be ineffective against A. fumigatus.

PMID- 17178788
TI  - c-Fos-deficient mice are susceptible to Salmonella enterica serovar Typhimurium
      infection.
AB  - c-Fos is a component of transcription factor AP-1. We show that macrophages
      lacking c-Fos exhibit enhanced production of proinflammatory cytokines,
      potentiated NF-kappaB phosphorylation, and increased cell death following
      Salmonella enterica serovar Typhimurium infection. Furthermore, mice lacking c
      Fos are highly susceptible to infection, suggesting that c-Fos confers resistance
      to Salmonella infection in mice.

PMID- 17178789
TI  - Induction of host chemotactic response by Encephalitozoon spp.
AB  - Microsporidians are a group of emerging pathogens typically associated with
      chronic diarrhea in immunocompromised individuals. The number of reports of
      infections with these organisms and the disseminated pathology is growing as
      diagnostic tools become more readily available. However, little is known about
      the innate immune response induced by and generated against these parasites.
      Using a coculture chemotaxis system, primary human macrophages were infected with
      Encephalitozoon cuniculi or Encephalitozoon intestinalis, and the recruitment of
      naive monocytes was monitored. Encephalitozoon spp. induced an average threefold
      increase in migration of naive cells 48 h postinfection, which corresponded to
      optimal infection of monocyte-derived-macrophages. A limited microarray analysis
      of infected macrophages revealed several chemokines involved in the inflammatory
      responses whose expression was upregulated, including CCL1, CCL2, CCL3, CCL4,
      CCL7, CCL15, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, and CXCL8. The levels of 6 of 11
      chemokines also present in the microarray were confirmed to be elevated by
      protein profiling. Kinetic studies confirmed that secreted CCL2, CCL3, and CCL4
      were expressed as early as 6 h postinfection, with peak expression at 12 to 24 h
      and expression remaining until 48 h postinfection. Neutralization of these
      chemokines, specifically CCL4, significantly reduced the number of migrating
      cells in vitro, indicating their role in the induction of monocyte migration.
      This mechanism of recruitment not only supports the evidence that in vivo
      cellular infiltration occurs but also provides new hosts for the parasites, which
      escape macrophages by rupturing the host cell. To our knowledge, this is the
      first documentation that chemokine production is induced by microsporidian
      infections in human macrophages.

PMID- 17178791
TI  - Mosaic tetracycline resistance genes are widespread in human and animal fecal
      samples.
AB  - Mosaic tetracycline resistance genes comprising tet(O), tet(W), and tet(32)
      sequences were abundant in DNA extracted from pig and human fecal samples,
      accounting for 78% (50/64) and 46% (37/80) of genes amplified with a tet(O)
      primer set, respectively, in two samples. The nonmosaic tet(32) gene was isolated
      from a human saliva bacterium.

PMID- 17178790
TI  - Role of RpoS in fine-tuning the synthesis of Vi capsular polysaccharide in
      Salmonella enterica serotype Typhi.
AB  - Regulation of the synthesis of Vi polysaccharide, a major virulence determinant
      in Salmonella enterica serotype Typhi, is under the control of two regulatory
      systems, ompR-envZ and rscB-rscC, which respond to changes in osmolarity. Some
      serotype Typhi strains exhibit overexpression of Vi polysaccharide, which masks
      clinical detection of lipopolysaccharide O antigen. This variation in Vi
      polysaccharide and O antigen display (VW variation) has been observed since the
      initial studies of serotype Typhi. In this study, we report that rpoS plays a
      role in this increased expression in Vi polysaccharide. We constructed a variety
      of isogenic serotype Typhi mutants that differed in their expression levels of
      RpoS and examined the role of the rpoS product in synthesis of Vi polysaccharide
      under different osmolarity conditions. Vi polysaccharide synthesis was also
      examined in serotype Typhi mutants in which the native promoter of the rpoS was
      replaced by an araCP(BAD) cassette, so that the expression of rpoS was arabinose
      dependent. The RpoS(-) strains showed increased syntheses of Vi polysaccharide,
      which at low and medium osmolarities masked O antigen detection. In contrast,
      RpoS(+) strains showed lower syntheses of Vi polysaccharide, and an increased
      detection of O antigen was observed. During exponential growth, when rpoS is
      unstable or present at low levels, serotype Typhi RpoS(+) strains overexpress the
      Vi polysaccharide at levels comparable to those for RpoS(-) strains. Our results
      show that RpoS is another regulator of Vi polysaccharide synthesis and
      contributes to VW variation in serotype Typhi, which has implications for the
      development of recombinant attenuated Salmonella vaccines in humans.

PMID- 17178792
TI  - Impact of nevirapine (NVP) plasma concentration on selection of resistant virus
      in mothers who received single-dose NVP to prevent perinatal human
      immunodeficiency virus type 1 transmission and persistence of resistant virus in
      their infected children.
AB  - Nonnucleoside reverse transcriptase inhibitor resistance following the use of
      single-dose nevirapine (sdNVP) for the prevention of mother-to-child transmission
      (PMTCT) remains a concern. In the ANRS-1201/1202 Ditrame study, conducted in
      Abidjan, Cote d'Ivoire, a short-course regimen of zidovudine was associated with
      sdNVP for PMTCT. In this study, we estimate the frequency of NVP resistance and
      its relationship with NVP concentration in mothers. Genotypic resistance analysis
      was performed on mothers' plasma samples at week 4 postpartum (PP) and on human
      immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMC)
      when an NVP resistance mutation was detected. The same tests were performed for
      the infected children at week 4, month 3, and month 12. Mothers' NVP plasma
      concentrations were measured at 48 h PP. Twenty-one (33%) of the 63 women
      selected had NVP-resistant (NVP-R) virus at week 4 PP. The median plasma NVP
      concentration was 598 ng/ml for the mothers without NVP-R virus compared to 851
      ng/ml for the mothers harboring NVP-R virus (P = 0.014). NVP-R mutations were
      detected in the HIV DNA of 15/20 women. Plasma NVP-R mutations were detectable in
      6 of 26 infected children at week 4. All 6 children had detectable NVP-R
      mutations in HIV DNA of PBMC. Blood samples taken at month 3 (1 child) and month
      12 (1 child) revealed the persistence of NVP-R mutations in plasma and cells.
      Emergence of NVP-R virus in mothers is strongly correlated with a high level of
      plasma NVP concentration, owing to a prolonged postpartum period of viral
      replication under NVP selective pressure. The follow-up of the cohort
      demonstrates the prolonged archive of resistant virus.

PMID- 17178793
TI  - Comparison of itraconazole and fluconazole treatments in a murine model of
      coccidioidal meningitis.
AB  - Coccidioidal meningitis (CM) is a devastating disease that requires long-term
      therapy and for which there is little hope of a cure. A model was used to compare
      the efficacies of itraconazole and fluconazole. CD-1 mice were infected
      intrathecally with 30 to 36 viable arthroconidia of Coccidioides. Oral therapy
      with cyclodextrin (control) or itraconazole or fluconazole at 10, 25, or 50 mg/kg
      of body weight twice daily (BID) was given for 12 days, from day 3 of infection.
      Treatment with both antifungals at all doses prolonged survival compared with
      that of the control treatment (P < 0.01 to 0.0001). At 50 mg/kg, itraconazole and
      fluconazole were equivalent, whereas itraconazole at 10 or 25 mg/kg prolonged
      survival compared to that achieved with fluconazole at these dosages (P < 0.05
      and 0.01, respectively). Early histologic analysis (10 days of treatment) with 50
      mg/kg BID itraconazole or fluconazole showed suppression of CM in all five
      animals per group; in quantitative cultures, three of three animals from each
      group had no detectable infection in the brain, spinal cord, or a site of
      secondary infection, the lungs. In contrast, four of seven controls showed mild
      to severe meningitis, with arteritis detected in three animals. In a short-term
      organ clearance study, 5 days of treatment with 10 or 50 mg/kg BID itraconazole
      or fluconazole reduced the tissue burdens in the brain and spinal cord compared
      to the tissue burdens in the controls (P < 0.02 to 0.0003). Fluconazole at 10
      mg/kg did not reduce the fungal burden in secondary sites, the lungs and kidneys,
      whereas this itraconazole dose was more effective in clearing the fungi from both
      organs (P < 0.05 and P < 0.001, respectively). At 50 mg/kg, itraconazole and
      fluconazole were equivalent in clearing the fungi from the brain and kidney, but
      itraconazole was superior to fluconazole in clearing the fungi from the spinal
      cord and lungs (P < 0.05). Thus, both itraconazole and fluconazole were effective
      at controlling CM, but neither eliminated Coccidioides from tissues. Overall,
      itraconazole was more efficacious on an mg/kg basis; at high doses they were
      similarly effective.

PMID- 17178794
TI  - Synergistic activity of R207910 combined with pyrazinamide against murine
      tuberculosis.
AB  - In previous studies, the diarylquinoline R207910 (also known as TMC207) was
      demonstrated to have high bactericidal activity when combined with first- or
      second-line antituberculous drugs. Here we extend the evaluation of R207910 in
      the curative model of murine tuberculosis by assessing the activities of one-,
      two-, and three-drug combinations containing R207910 and isoniazid (INH),
      rifampin (RIF), pyrazinamide (PZA), or moxifloxacin (MXF) in the setting of a
      high initial bacillary load (7.2 log(10) CFU). Two months of treatment with the
      combinations R207910-PZA, R207910-PZA-INH, R207910-PZA-RIF, or R207910-PZA-MXF
      resulted in culture-negative lung homogenates in 70 to 100% of the mice, while
      mice treated with INH-RIF-PZA (the reference regimen) or RIF-MXF-PZA remained
      culture positive. Combinations including R207910 but not PZA (e.g., R207910-INH
      RIF and R207910-MXF-RIF) were less active than R207910-PZA-containing regimens
      administered either alone or with the addition of INH, RIF, or MXF. These results
      reveal a synergistic interaction between R207910 and PZA. Three-drug combinations
      containing these two drugs and INH, RIF, or MXF have the potential to
      significantly shorten the treatment duration in patients, provided that these
      results can be confirmed in long-term experiments including periods of relapse.

PMID- 17178795
TI  - In vitro activities of cloxyquin (5-chloroquinolin-8-ol) against Mycobacterium
      tuberculosis.
AB  - The in vitro activities of cloxyquin (5-chloroquinolin-8-ol) against 9 standard
      strains and 150 clinical isolates of Mycobacterium tuberculosis were studied. The
      MICs ranged from 0.062 to 0.25 microg/ml. The MIC(50) and MIC(90) were 0.125 and
      0.25 microg/ml, respectively. These indicate that cloxyquin exhibited good
      antituberculosis activity, even for multidrug-resistant isolates.

PMID- 17178797
TI  - Expression of immunomodulatory genes in human monocytes induced by voriconazole
      in the presence of Aspergillus fumigatus.
AB  - We assessed the effect of voriconazole (VRC) on the expression and release of
      selected cytokines and chemokines in the THP-1 human monocytic cell line in
      response to Aspergillus fumigatus hyphal fragments (HF) by cDNA microarray
      analysis, reverse transcriptase (RT) PCR, and enzyme-linked immunosorbent assay.
      Stimulation of THP-1 cells by HF alone caused a significant up-regulation of CCL4
      (MIP1B) and CCL16, while CCL2 (MCP1) was down-regulated. By comparison, in the
      presence of VRC, a large number of genes such as CCL3 (MIP1A), CCL4 (MIP1B), CCL5
      (RANTES), CCL7 (MCP3), CCL11 (EOTAXIN), CCL15 (MIP1Delta), CXCL6, and CXCL13 were
      strongly up-regulated in THP-1 cells challenged by HF, whereas CCL20 (MIP3A) and
      CCL21 (MIP2) were down-regulated. Among five genes differentially expressed in
      THP-1 cells, IL12A, IL12B, and IL-16 were down-regulated whereas IL-11 and TGFB1
      were significantly up-regulated in the presence of VRC. The inflammation-related
      genes IFNgamma, IL1R1, and TNFA were also up-regulated in THP-1 cells exposed to
      HF only in the presence of VRC. RT-PCR of four selected genes validated the
      results of microarrays. The release of interleukin 1beta (IL-1beta) and IL-12 was
      significantly increased from monocytes stimulated either by HF alone (P < 0.05)
      or in the presence of VRC (P < 0.01 and P < 0.05, respectively). In contrast,
      tumor necrosis factor alpha release from monocytes was enhanced only in the
      presence of VRC (P < 0.01). The chemokines monocyte chemoattractant protein 1 and
      macrophage inflammatory protein 1beta were decreased under both conditions (P <
      0.01). These results demonstrate that in the presence of VRC, HF induces a more
      pronounced profile of gene expression in THP-1 cells than HF alone, potentially
      leading to more-efficient host resistance to A. fumigatus.

PMID- 17178796
TI  - Two-year assessment of entecavir resistance in Lamivudine-refractory hepatitis B
      virus patients reveals different clinical outcomes depending on the resistance
      substitutions present.
AB  - Entecavir (ETV) is a deoxyguanosine analog approved for use for the treatment of
      chronic infection with wild-type and lamivudine-resistant (LVDr) hepatitis B
      virus (HBV). In LVD-refractory patients, 1.0 mg ETV suppressed HBV DNA levels to
      below the level of detection by PCR (<300 copies/ml) in 21% and 34% of patients
      by Weeks 48 and 96, respectively. Prior studies showed that virologic rebound due
      to ETV resistance (ETVr) required preexisting LVDr HBV reverse transcriptase
      substitutions M204V and L180M plus additional changes at T184, S202, or M250. To
      monitor for resistance, available isolates from 192 ETV-treated patients were
      sequenced, with phenotyping performed for all isolates with all emerging
      substitutions, in addition to isolates from all patients experiencing virologic
      rebounds. The T184, S202, or M250 substitution was found in LVDr HBV at baseline
      in 6% of patients and emerged in isolates from another 11/187 (6%) and 12/151
      (8%) ETV-treated patients by Weeks 48 and 96, respectively. However, use of a
      more sensitive PCR assay detected many of the emerging changes at baseline,
      suggesting that they originated during LVD therapy. Only a subset of the changes
      in ETVr isolates altered their susceptibilities, and virtually all isolates were
      significantly replication impaired in vitro. Consequently, only 2/187 (1%)
      patients experienced ETVr rebounds in year 1, with an additional 14/151 (9%)
      patients experiencing ETVr rebounds in year 2. Isolates from all 16 patients with
      rebounds were LVDr and harbored the T184 and/or S202 change. Seventeen other
      novel substitutions emerged during ETV therapy, but none reduced the
      susceptibility to ETV or resulted in a rebound. In summary, ETV was effective in
      LVD-refractory patients, with resistant sequences arising from a subset of
      patients harboring preexisting LVDr/ETVr variants and with approximately half of
      the patients experiencing a virologic rebound.

PMID- 17178798
TI  - Assessment of the effect of mefloquine on artesunate pharmacokinetics in healthy
      male volunteers.
AB  - The effect of mefloquine on artesunate pharmacokinetics was assessed in 20
      volunteers given artesunate for 3 days, followed > or =21 days later by
      combination therapy for 3 days. The areas under the concentration-time curve from
      0 h to infinity for dihydroartemisinin, the active metabolite of artesunate, were
      similar on day 3 of the two dosing periods (P = 0.12), implying no interaction.

PMID- 17178799
TI  - Inhibition of Plasmodium falciparum oocyst production by membrane-permeant
      cysteine protease inhibitor E64d.
AB  - During asexual intraerythrocytic growth, Plasmodium falciparum utilizes
      hemoglobin obtained from the host red blood cell (RBC) as a nutrient source.
      Papain-like cysteine proteases, falcipains 2 and 3, have been reported to be
      involved in hemoglobin digestion and are targets of current antimalarial drug
      development efforts. However, their expression during gametocytogenesis, which is
      required for malaria parasite transmission, has not been studied. Many of the
      available antimalarials do not inhibit development of sexual stage parasites, and
      therefore, the persistence of gametocytes after drug treatment allows continued
      transmission of the disease. In the work reported here, incubation of stage V
      gametocytes with membrane-permeant cysteine protease inhibitor E64d significantly
      inhibited oocyst production (80 to 100%). The same conditions inhibited
      processing of gametocyte-surface antigen Pfs230 during gametogenesis but did not
      alter the morphology of the food vacuole in gametocytes, inhibit emergence, or
      block male exflagellation. E64d reduced the level of oocyst production more
      effectively than that reported previously for falcipain 1-knockout parasites,
      suggesting that falcipains 2 and 3 may also be involved in malaria parasite
      transmission. However, in this study only falcipain 3 and not falcipain 2 was
      found to be expressed in stage V gametocytes. Interestingly, during
      gametocytogenesis falcipain 3 was transported into the red blood cell and by
      stage V was localized in vesicles along the RBC surface, consistent with a role
      during gamete emergence. The ability of a membrane-permeant cysteine protease
      inhibitor to significantly reduce malaria parasite transmission suggests that
      future drug design should include evaluation of gametogenesis and sporogonic
      development.

PMID- 17178800
TI  - Detection of a new SHV-type extended-spectrum beta-lactamase, SHV-31, in a
      Klebsiella pneumoniae strain causing a large nosocomial outbreak in The
      Netherlands.
AB  - A Klebsiella pneumoniae strain resistant to third-generation cephalosporins was
      isolated in the eastern Netherlands. The strain was found to carry a novel
      extended-spectrum beta-lactamase, namely, SHV-31. The combination of the two
      mutations by which SHV-31 differs from SHV-1, namely, L35Q and E240K, had
      previously only been described in association with one or more additional
      mutations.

PMID- 17178801
TI  - Quinoline derivative MC1626, a putative GCN5 histone acetyltransferase (HAT)
      inhibitor, exhibits HAT-independent activity against Toxoplasma gondii.
AB  - We report that quinoline derivative MC1626, first described as an inhibitor of
      the histone acetyltransferase (HAT) GCN5, is active against the protozoan
      parasite Toxoplasma gondii in vitro. However, MC1626 does not inhibit Toxoplasma
      GCN5 HATs or reduce HAT-mediated activity; rather, this quinoline may target the
      plastid organelle called the apicoplast.

PMID- 17178802
TI  - Influence of dietary endophyte (Neotyphodium coenophialum)-infected tall fescue
      (Festuca arundinacea) seed on fecal shedding of antibiotic resistance-selected
      Escherichia coli O157:H7 in ewes.
AB  - The objectives were to determine the effects of short-term feeding of a toxic
      endophyte (Neotyphodium coenophialum)-infected tall fescue seed (Festuca
      arundinacea, cultivar 'Kentucky 31') on fecal shedding and intestinal
      concentrations of Escherichia coli O157:H7 and the concentrations of prolactin,
      cortisol, and NEFA in experimentally inoculated ewes. Twelve ewes (mean BW = 46
      +/- 2 kg) were fed a diet containing either high endophyte-infected (HI-E) or low
      endophyte-infected (LO-E) tall fescue seed for 7 d. Each diet consisted of 50%
      (as-fed basis) tall fescue seed. Ewes were experimentally inoculated with
      antibiotic resistance-selected E. coli O157:H7 on d 1 of the feeding treatment,
      and fecal shedding of inoculated pathogens was monitored daily on d 2 to 6. On d
      7, ewes were weighed and euthanized, and tissues and contents were sampled from
      the ileum, cecum, and rectum for quantitative enumeration of E. coli O157:H7.
      Urine was collected at euthanization to determine total ergot alkaloid
      concentrations. Ewes fed HI-E had lower (P < 0.001) DMI than did ewes fed LO-E
      (0.8 and 1.6 +/- 0.1 kg/d of DMI for HI-E and LO-E ewes, respectively);
      consequently, there was a tendency (P = 0.06) for HI-E ewes to lose 0.3 +/- 0.4
      kg of BW/d and LO-E ewes to gain 0.2 +/- 0.4 kg of BW/d during the 7 d. Urinary
      ergot alkaloids were increased (P < 0.001) in ewes fed HI-E (47.8 +/- 9.4 ng/mg
      of creatinine) compared with those fed LO-E (6.2 +/- 9.4 ng/mg of creatinine).
      Prolactin tended (P = 0.06) to be decreased in ewes fed HI-E (7.2 +/- 7.0 ng/mL)
      compared with those fed LO-E (27.7 +/- 7.0 ng/mL). Fecal shedding of E. coli
      O157:H7 tended (P = 0.06) to be increased in HI-E ewes [5.4 cfu (log10)/g of
      feces] compared with LO-E ewes [4.5 cfu (log10)/g of feces]. The population of E.
      coli O157:H7 in luminal contents from the ileum, cecum, and rectum did not differ
      (P > 0.36) between treatments. Treatment did not influence (P = 0.30) the
      occurrence of E. coli O157:H7 in cecal or rectal tissues; however, ileal tissues
      from HI-E ewes tended (P = 0.12) to have an increased incidence of E. coli
      O157:H7. Concentrations of NEFA tended (P = 0.12) to be greater in HI-E ewes than
      in LO-E ewes, whereas cortisol was similar (P = 0.49) for HI-E and LO-E ewes. We
      conclude that short-term feeding of HI-E tall fescue seed may alter the
      concentrations of prolactin and NEFA, and may increase fecal shedding of E. coli
      O157:H7 in experimentally inoculated ewes.

PMID- 17178803
TI  - Imprinted status of pleomorphic adenoma gene-like I and paternal expression gene
      10 genes in pigs.
AB  - Genomic imprinting is theorized to exist in all placental mammals and some
      marsupials. Imprinted genes play important roles in the regulation of fetal
      growth, development, and postnatal behavior, but the study of imprinted genes has
      been limited in livestock. In this study, the polymorphism-based approach was
      used to detect the expression patterns of the porcine pleomorphic adenoma gene
      like I (PLAGL1) and paternal expression gene 10 (PEG10) genes. Single nucleotide
      polymorphisms in the exons were detected between the Meishan and Large White
      breeds in the PLAGL1 and PEG10 genes. The polymorphisms were used to determine
      the monoallelic or biallelic expression with reverse transcription-PCR-RFLP in 44
      tissues from 4 heterozygous pigs (based on SNP). Imprinting analysis indicated
      that the PLAGL1 and PEG10 genes were both paternally expressed in all tissues
      tested (heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal
      muscle, fat, uterus, and ovary). Our study showed that the method of identifying
      polymorphic transcripts with reverse transcription-PCR-RFLP may be beneficial for
      detecting the imprinting status of some candidate imprinted genes.

PMID- 17178804
TI  - Accounting for outliers and heteroskedasticity in multibreed genetic evaluations
      of postweaning gain of Nelore-Hereford cattle.
AB  - The objectives of this study were to demonstrate the utility of hierarchical
      Bayesian models combining residual heteroskedasticity with robustness for outlier
      detection and muting and to evaluate the effects of such joint modeling in
      multibreed genetic evaluations. A 3 x 2 factorial specification of 6 residual
      variance models based on several distributional (Gaussian, Student's t, or Slash)
      and variability (homoskedastic or heteroskedastic) assumptions was used to
      analyze 22,717 postweaning gain records from a Nelore-Hereford population (40,082
      animals in the pedigree). To illustrate the utility of the 2 robust
      distributional specifications (Student's t and Slash) for outlier detection and
      muting, 3 records from the same contemporary group (an extreme residual outlier,
      a mild residual outlier, and a near-zero residual) were chosen for further study.
      The posterior densities of the corresponding weighting variables of these records
      were used to assess their degree of Gaussian outlyingness and the ability of the
      robust models to mute the effects of deviant records. The Student's t
      heteroskedastic provided the best-fit model among the 6 specifications and was
      preferred for genetic merit inference. Kendall rank correlations of the posterior
      means of the additive genetic effects of the animals, used to compare the
      selection order of the Student's t and Gaussian models, were reasonably high
      across all animals within the most frequent genotypes, ranging from 0.83 to 0.91
      and from 0.89 to 0.95 for the homoskedastic and the heteroskedastic versions,
      respectively. However, when considering only animals ranked in the top 10% by the
      customary Gaussian homoskedastic model, these rank correlations were reduced
      considerably, ranging from 0.29 to 0.57 and from 0.72 to 0.85 between the 2
      residual densities within the homoskedastic and heteroskedastic versions,
      respectively. Rank correlations between the homoskedastic and heteroskedastic
      versions within each of the Gaussian and Student's t error models tended to be
      smaller, with a range from 0.68 to 0.90 across all animals and from 0.28 to 0.67
      for animals ranked in the top 10%. These results support the implementation of
      robust models accounting for sources of heteroskedasticity to increase the
      precision and stability of multibreed genetic evaluations with proper statistical
      treatment of deviant records.

PMID- 17178805
TI  - Growth, carcass quality, and protein and energy metabolism in beef cattle with
      different growth potentials and residual feed intakes.
AB  - Twenty-four beef steers (predominantly Angus x Hereford, 14 to 18 mo of age, 403
      +/- 3 kg of BW), were housed and fed in individual pens for about 122 d. Twelve
      steers came from a herd that had been selected for growth (high growth; HG) and
      the other 12 from a herd with no selection program (low growth; LG). Another 6
      steers (3 from each group) were slaughtered at the beginning to obtain the
      initial composition. All steers were fed the same corn-based diet (3.06 Mcal of
      ME/kg of DM, 13.6% CP) on an ad libitum basis. Two weeks before slaughter, total
      urine was collected for 5 d for estimation of 3-methylhistidine excretion and
      myofibrillar protein breakdown rates. Compared with LG steers, HG steers had less
      initial BW but greater final BW, DMI (7.52 vs. 6.37 kg/d), ADG (1.33 vs. 0.853
      kg/d), G:F (0.176 vs. 0.133 kg/kg), ME intake (0.233 vs. 0.201 Mcal x kg of
      BW(0.75) x d(-1)), and retained energy (RE; 0.0711 vs. 0.0558 Mcal x kg of
      BW(0.75) x d(-1)); gained more fat (676 vs. 475 g/d); and tended to gain more
      whole body protein (100 vs. 72 g/d), with no difference in residual feed intake
      (RFI). Estimated net energetic efficiency of gain (k(g)) and ME for maintenance
      (ME(m)) did not differ between the 2 groups, averaging 0.62 and 0.114,
      respectively. The HG steers had greater HCW (350 vs. 329 kg), backfat (16.1 vs.
      11.6 mm), and yield grades (3.53 vs. 2.80), with a similar dressing percent, KPH
      fat, LM area, and marbling score. Skeletal muscle protein gain (70.2 vs. 57.6
      g/d) and fractional protein accretion rate (0.242 vs. 0.197%/d) tended to be
      greater in HG than in LG steers. Steers were classified into low (-0.367 kg/d)
      and high (0.380 kg/d) RFI classes. Compared with the high RFI steers, low RFI
      steers consumed less DM (6.61 vs. 7.52 kg/d) and ME (0.206 vs. 0.234 Mcal x kg of
      BW(0.75) x d(-1)) and tended to gain less fat (494 vs. 719 g/d), but were similar
      for initial and final BW, ADG, G:F, protein gain, HCW, dressing percent, backfat,
      KPH fat, LM area, marbling score, and yield grade, as well as for all
      observations related to myofibrillar protein metabolism. Residual feed intake may
      be positively [corrected] correlated with ME for maintenance. The maintenance
      energy requirement increased by 0.0166 Mcal x kg(-0.75) x d(-1) for each
      percentage increase in fractional protein degradation rate, confirming the
      importance of this process in the energy economy of the animal.

PMID- 17178806
TI  - The effect of fermentation quality on the voluntary intake of grass silage by
      growing cattle fed silage as the sole feed.
AB  - This study was designed to separate the effect of fermentation quality on
      voluntary intake of grass silage from other feed factors affecting intake.
      Variations in DMI were quantified, and the impact on intake was modeled. The
      relationships between individual silage components and intake were examined. A
      partially balanced changeover experiment with 30 Norwegian Red steers (137 +/-
      16.4 kg of BW) was carried out to determine the intake of 24 silages and of hay
      harvested from the same parent crop within 60 h. Five forages were fed at a time
      in each of five 3-wk periods. Every 3-wk period was preceded by 2 wk of feeding a
      standard silage. Silage DMI ranged from 1.79 to 2.65, with a mean of 2.38 kg x
      100 kg of BW(-1) x d(-1). Hay DMI averaged 2.43 kg x 100 kg of BW(-1) x d(-1).
      Ranges (mean) for the composition of silages were as follows: DM, 166 to 237
      (213) g/kg; water-soluble carbohydrates, 16.3 to 70.9 (33.0) g/kg of DM; acetic
      acid, 11.5 to 64.7 (28.6) g/kg of DM; propionic acid, 0 to 5.2 (1.0) g/kg of DM;
      butyric acid, 0 to 25.1 (6.0) g/kg of DM; lactic acid, 2.2 to 102 (49.3) g/kg of
      DM; and NH3-N (not corrected for additive-derived N), 89.3 to 255 (153) g/kg of
      total N. Silage DMI was closely (P < 0.05) related to DM, ADL, VFA, lactic acid,
      total acids, the lactic acid:total acids ratio, ADIN, NH3-N (not corrected),
      histamine, tryptamine, cadaverine, and the total sum of amines (the explained
      variation in intake ranged from 14 to 53%). The 2 best models describing silage
      DMI included concentrations in the silage of propionic acid, butyric acid, and
      lactic acid, and these models explained 75 and 84% of the variation in DMI. The
      strong correlation (r = 0.84, P < 0.05) between total NH3-N and butyric acid
      concentrations in silages indicates that these variables described the same
      variation pattern. The inclusion of NH3-N in the equations describing the effect
      of fermentation quality on DMI of low-DM grass silage was less useful than that
      of butyric acid. This was due to the confounded relationship between the NH3-N
      concentration in silages and the use of ammonium-containing preservatives and to
      difficulties in correcting for the added ammonium.

PMID- 17178807
TI  - Leucine stimulates mammalian target of rapamycin signaling in C2C12 myoblasts in
      part through inhibition of adenosine monophosphate-activated protein kinase.
AB  - Mammalian target of rapamycin (mTOR) signaling is one of the main signaling
      pathways controlling protein synthesis. Leucine treatment upregulates mTOR
      signaling, which enhances protein synthesis; however, the mechanisms are not well
      understood. Herein, treatment of C2C12 myoblast cells with leucine enhanced the
      phosphorylation of mTOR and ribosomal protein S6 kinase. Leucine treatment also
      decreased the adenosine monophosphate/ATP ratio in myoblasts by 36.4 +/- 9.1% (P
      < 0.05) and reduced the phosphorylation of adenosine monophosphate-activated
      protein kinase (AMPK) alpha subunit at Thr172 (28.6 +/- 4.9% reduction, P < 0.05)
      and inhibited AMPK activity (43.6 +/- 3.5% reduction, P < 0.05). In addition,
      leucine increased the phosphorylation of mTOR at Ser2448 by 63.5 +/- 10.0% (P <
      0.05) and protein synthesis by 30.6 +/- 6.1% (P < 0.05). Applying 5
      aminoimidazole-4-carbox-amide 1-beta-d-ribonucleoside, an activator of AMPK,
      abolished the stimulation of mTOR signaling by leucine, showing that AMPK
      negatively controls mTOR signaling. To further show the role of AMPK in mTOR
      signaling, myoblasts expressing a dominant negative AMPKalpha subunit were
      employed. Negative myoblasts had very low AMPK activity. The activation of mTOR
      induced by leucine in these cells was abated, showing that AMPK contributed to
      mTOR activation. In conclusion, leucine stimulates mTOR signaling in part through
      AMPK inhibition. This study implicates AMPK as an important target for
      nutritional management to enhance mTOR signaling and protein synthesis in muscle
      cells, thereby increasing muscle growth.

PMID- 17178808
TI  - Effects of supplemental manganese on performance of growing-finishing pigs and
      pork quality during retail display.
AB  - Crossbred barrows and gilts (n = 168) were used to test the effects of
      supplemental Mn during the growing-finishing period on performance, pork carcass
      characteristics, and pork quality during 7 d of retail display. Pigs were blocked
      by BW and allotted within blocks to pens (5 pigs/pen in blocks 1, 2, 5, and 6,
      and 4 pigs/pen in blocks 3 and 4). A total of 36 pens was randomly assigned to 1
      of 6 dietary treatments, where the basal diets were formulated with (PC) or
      without (NC) Mn in the mineral premix, and supplemented with 0 or 350 ppm (as-fed
      basis) of Mn from MnSO4 or a Mn-AA complex (AvMn). Pigs were slaughtered at a
      commercial pork packing plant when the lightest block of pigs averaged 113.6 kg.
      During fabrication, boneless pork loins were collected and transported to
      Oklahoma State University, where 2.5-cm-thick LM chops were packaged in a
      modified atmosphere (80% O2 and 20% CO2) and subsequently placed in display cases
      (2 to 4 degrees C) under continuous fluorescent lighting (1,600 lx) for 7 d. Pig
      performance was not (P > or = 0.44) affected by supplemental Mn; however, during
      the grower-II phase, pigs fed the basal diets including Mn consumed less (P <
      0.02) feed and tended to be more efficient (P < 0.09) than pigs fed the basal
      diets devoid of Mn. Throughout the entire feeding trial, neither dietary nor
      supplemental Mn altered (P > or = 0.22) ADG, ADFI, or G:F. Chops from pigs fed
      the diets supplemented with MnSO4 received greater (P < or = 0.05) lean color
      scores and had a redder (greater a* and hue angle values), more vivid color than
      chops from pigs fed the diets supplemented with AvMn. Additionally, LM chops from
      pigs fed the PC diets supplemented with MnSO4 were darker (lower L* values; P <
      0.05) than chops from pigs fed the NC diets or PC diets supplemented with 0 or
      350 ppm of AvMn. Even though discoloration scores were similar during the first 4
      d of display, chops from pigs fed the PC diets supplemented with MnSO4 were less
      (P < 0.05) discolored on d 6 and 7 of retail display than chops from pigs fed the
      PC or NC diets and diets supplemented with AvMn (dietary treatment x display
      time, P = 0.04). Results of this study indicate that feeding an additional 350
      ppm of Mn from MnSO4 above the maintenance requirements of growing-finishing pigs
      does not beneficially affect live pig performance but may improve pork color and
      delay discoloration of pork during retail display.

PMID- 17178809
TI  - Low-phytate barley cultivars improve the utilization of phosphorus, calcium,
      nitrogen, energy, and dry matter in diets fed to young swine.
AB  - A 28-d experiment was conducted using 45 crossbred barrows with an average
      initial BW of 9.5 kg and age of 35 d to evaluate low-phytate barley (LPB) mutants
      (M) M422, M635, and M955, which were hulled, near-isogenic progeny of the normal
      barley (NB) Harrington and had 47, 66, and 80% less phytic acid, respectively,
      than NB. A hull-less LPB, M422-H, which was not near-isogenic to the other
      cultivars, was also evaluated. Apparent nutrient balance, bone measurements, and
      growth performance were the response criteria evaluated. The barrows were fed the
      diets to appetite in meal form in individual metabolism crates. Barley and
      soybean meal were the only sources of phytic acid. Dietary protein
      supplementation and ME/kg were equalized in all diets. The treatments were diets
      containing NB, M422, M635, or M422-H without or with added inorganic P (iP), or
      M955 without added iP. Diets with added iP contained 0.30% available P (aP), the
      same concentration of aP provided by the diet containing M955 without added iP.
      There were linear increases (P < or = 0.02) in ADG, G:F, metacarpal and radius
      bone strength, and fat-free dry weight, and in the absorption and retention (g/d
      and % of intake) of P and Ca with increasing dietary concentration of aP from the
      near-isogenic cultivars NB, M422, M635, or M955 without added iP. There were
      linear decreases in the grams (P < or = 0.02) and percentages (P < 0.001) of P
      and Ca excreted per day with increasing dietary concentration of aP without added
      iP. There were no responses for N or energy balance. Growth performance and bone
      response criteria did not differ for barrows fed the diet containing M955 or the
      near-isogenic diets containing NB, M422, or M635 with added iP. However, barrows
      fed the diet containing M955 had greater (P < or = 0.02) percentages of P, N, and
      energy absorption and retention, Ca absorption, and DM digestibility and had less
      (P < or = 0.02, g/d and %) excretion of P, N, energy, and Ca (g) per day than
      barrows fed the diets containing the near-isogenic NB or LPB cultivars with added
      iP. When dietary aP was equalized with iP, the excretion of P in feces plus urine
      (g/d) was reduced by 20.2, 27.9, and 44.6%, respectively, in barrows fed the
      diets containing M422 + iP, M635 + iP, or M955 compared with barrows fed the diet
      containing NB + iP. Energy utilization did not differ for barrows fed the diets
      containing hulled or hull-less LPB when ME/kg was equalized with lard. In
      conclusion, the apparent utilization of P and Ca, the bone strength and fat-free
      dry weight, and growth performance increased with increasing dietary
      concentration of aP provided by LPB, in association with linear decreases in P
      and Ca excretion. Barrows fed the diet containing M955 also had greater
      utilization and less excretion of P, Ca, N, energy, and DM than barrows fed the
      diets containing the near-isogenic NB or LPB cultivars with added iP to equalize
      aP at 0.30%.

PMID- 17178810
TI  - Bioavailability of vitamin A sources for cattle.
AB  - An experiment was conducted to evaluate the bioavailability of 5 sources of
      vitamin A. It was hypothesized that some vitamin A products have protective
      coatings that are more resistant than others to rumen destruction and that such
      protection would result in greater tissue concentrations of vitamin A. Fifty
      three yearling Angus x Brahman cattle, consisting of 39 steers and 14 heifers,
      were stratified by BW and sex and randomly assigned to 6 high-concentrate diet
      groups receiving no vitamin A supplementation (control) or vitamin A supplemented
      from the following sources: Microvit A (Adisseo, Acworth, GA), Rovamix A (DSM,
      Parsippany, NJ), Sunvit A, Lutavit A, and Microvit A DLC (Adisseo). The vitamin A
      treatment groups were fed daily 80,000 IU of retinol/animal in a low-retinol
      concentrate diet (78.5% oats, 10% cottonseed hulls, 8% molasses, and 2%
      cottonseed meal; DM basis) and a free-choice, poor quality (low carotene) hay for
      84 d. Every 28 d, BW was determined and liver biopsies and plasma were collected
      and analyzed for retinol concentrations. All retinol treatments showed
      significant increases in liver retinol concentrations compared with control
      animals (P < 0.0001), which steadily decreased over time. At all collection
      times, Microvit A led to numerically, but not significantly, greater
      concentrations of retinol in liver than did all other treatments. However, at the
      end of the experiment, there was no significant difference in liver retinol
      concentration among Microvit A, Rovamix A, Lutavit A, and Microvit A DLC diets.
      When liver retinol concentrations at all collection times were considered,
      Microvit A and Rovamix A appeared to provide the most bioavailable vitamin A.

PMID- 17178811
TI  - Transdifferentiation of porcine satellite cells to adipoblasts with ciglitizone.
AB  - Ciglitizone, a class of thiazolidinediones, acts as a potent activator of the
      adipose differentiation program in established preadipose cell lines.
      Thiazolidinediones have also been investigated in diabetic patients and have been
      reported to act as peroxisome proliferator-activated receptor-gamma ligands.
      Intramuscular adipogenesis or marbling through transdifferentiation of satellite
      cells in cattle was successfully conducted earlier. In this report, the effects
      of ciglitizone on the differentiation pathway of porcine myogenic satellite cells
      was investigated. Semitendinosus muscle was aseptically taken from 10-d-old
      piglets under general anesthesia, and porcine satellite cells were obtained and
      grown to near confluence. Postconfluent cells (d 0) were further cultured in
      differentiation medium containing an adipogenic mixture plus ciglitizone (10
      microM) for 48 h. From d 2 onward, the cells were cultured only in the presence
      of ciglitizone until d 10. Controls were cultured in differentiation medium only.
      Exposure of porcine satellite cells to the adipogenic mixture plus ciglitizone
      generated lipid droplets on d 2, and subsequently, exposure of cells to
      ciglitizone alone helped in cytoplasmic lipid filling, providing them with the
      acquisition of adipocyte morphology. An increase (P < 0.05) in the fusion
      (structures containing 2 to 3 nuclei) of satellite cells was observed, and myosin
      heavy chain appeared with greater intensity (immunohistochemistry) in the control
      group from d 2 onward. Adipocyte-specific transcriptional factors (i.e.,
      CCAAT/enhancer binding protein-alpha and peroxisome proliferator-activated
      receptor-gamma) were predominant during transdifferentiation and were observed
      with immunohistochemistry, Western blot (approximately 47.2 and approximately
      60.4 kDa, respectively), and real-time PCR. Ciglitizone appeared to convert the
      differentiation pathway of satellite cells into that of adipoblasts.

PMID- 17178812
TI  - Effect of undegradable intake protein supplementation on intake, digestion,
      microbial efficiency, in situ disappearance, and plasma hormones and metabolites
      in steers fed low-quality grass hay.
AB  - Four ruminally and duodenally cannulated beef steers (492 +/- 30 kg) were used in
      a 4 x 4 Latin square design to evaluate the effect of undegradable intake protein
      (UIP) supplementation on intake, digestion, microbial efficiency, in situ
      disappearance, and plasma hormones and metabolites in steers fed low-quality
      grass hay. The steers were offered chopped (10.2 cm in length) grass hay (6.0%
      CP) ad libitum and 1 of 4 supplements. Supplemental treatments (1,040 g of DM
      daily), offered daily at 0800, were control (no supplement) or low, medium, or
      high levels of UIP (the supplements provided 8.3, 203.8, and 422.2 g of UIP/ d,
      respectively). The supplements were formulated to provide similar amounts of
      degradable intake protein (22%) and energy (1.77 Mcal of NE(m)/kg). Blood samples
      were taken at -2, -0.5, 1, 2, 4, 8, 12, and 24 h after supplementation on d 1
      (intensive sampling) and at -0.5 h before supplementation on d 2, 3, 4, and 5
      (daily sampling) of each collection period. Contrasts comparing control vs. low,
      medium, and high; low vs. medium and high; and medium vs. high levels of UIP were
      conducted. Apparent and true ruminal OM and N digestion increased (P < 0.03) in
      steers fed supplemental protein compared with controls, but there were no
      differences (P > 0.26) among supplemental protein treatments. There were no
      differences (P > 0.11) among treatments for NDF or ADF digestion, or total
      ruminal VFA or microbial protein synthesis. Ruminal pH was not different (P =
      0.32) between control and protein-supplemented treatments; however, ruminal pH
      was greater (P = 0.02) for supplementation with medium and high compared with low
      UIP. Daily plasma insulin concentrations were increased (P = 0.004) in protein
      supplemented steers compared with controls and were reduced (P = 0.003) in steers
      fed low UIP compared with steers fed greater levels of UIP. Intensive and daily
      plasma urea N concentrations were increased (P < 0.01) in protein-supplemented
      steers compared with controls and increased (P < 0.02) for intensive and daily
      sampling, respectively, in steers supplemented with medium and high UIP compared
      with low UIP. Supplemental protein increased apparent and true ruminal OM and N
      digestion, and medium and high levels of UIP increased ruminal pH compared with
      the low level. An increasing level of UIP increases urea N and baseline plasma
      insulin concentrations in steers fed low-quality hay.

PMID- 17178813
TI  - Validation of commercial DNA tests for quantitative beef quality traits.
AB  - Associations between 3 commercially available genetic marker panels (GeneSTAR
      Quality Grade, GeneSTAR Tenderness, and Igenity Tender-GENE) and quantitative
      beef traits were validated by the US National Beef Cattle Evaluation Consortium.
      Validation was interpreted to be the independent confirmation of the associations
      between genetic tests and phenotypes, as claimed by the commercial genotyping
      companies. Validation of the quality grade test (GeneSTAR Quality Grade) was
      carried out on 400 Charolais x Angus crossbred cattle, and validation of the
      tenderness tests (GeneSTAR Tenderness and Igenity Tender-GENE) was carried out on
      over 1,000 Bos taurus and Bos indicus cattle. The GeneSTAR Quality Grade marker
      panel is composed of 2 markers (TG5, a SNP upstream from the start of the first
      exon of thyroglobulin, and QG2, an anonymous SNP) and is being marketed as a test
      associated with marbling and quality grade. In this validation study, the
      genotype results from this test were not associated with marbling score; however,
      the association of substituting favorable alleles of the marker panel with
      increased quality grade (percentage of cattle grading Choice or Prime) approached
      significance (P < or = 0.06), mainly due to the effect of 1 of the 2 markers. The
      GeneSTAR Tenderness and Igenity TenderGENE marker panels are being marketed as
      tests associated with meat tenderness, as assessed by Warner-Bratzler shear
      force. These marker panels share 2 common mu-calpain SNP, but each has a
      different calpastatin SNP. In both panels, there were highly significant (P <
      0.001) associations of the calpastatin marker and the mu-calpain haplotype with
      tenderness. The genotypic effects of the 2 tenderness panels were similar to each
      other, with a 1 kg difference in Warner-Bratzler shear force being observed
      between the most and least tender genotypes. Unbiased and independent validation
      studies are important to help build confidence in marker technology and also as a
      potential source of data required to enable the integration of marker data into
      genetic evaluations. As DNA tests associated with more beef production traits
      enter the marketplace, it will become increasingly important, and likely more
      difficult, to find independent populations with suitable phenotypes for
      validation studies.

PMID- 17178814
TI  - Changes in the histochemical properties and meat quality traits of porcine
      muscles during the growing-finishing period as affected by feed restriction,
      slaughter age, or slaughter weight.
AB  - In this study, the degree of contractile and metabolic development of myofibers
      in porcine LM, rectus femoris (RF), and dark and light portions of the
      semitendinosus (STD and STL, respectively) was determined, and their impact on
      meat quality was compared at the same age but different BW (trial 1) or at a
      given BW but different age (trial 2) in 48 Swiss Large White barrows from 12
      litters after the growing and finishing period. The barrows had ad libitum (A) or
      restricted (R, 80% of A) feed access. In trial 1, at 113 and 154 d of age, 6
      barrows in treatment A (62.1 and 99.5 kg of BW, respectively) and 6 siblings in
      treatment R (51.0 and 86.6 kg of BW, respectively) were slaughtered. In trial 2,
      a similar protocol was used except that the barrows were slaughtered at 61.3 (104
      or 119 d of age, respectively) or 101.3 kg of BW (145 or 167 d of age,
      respectively). Muscle fibers were stained and classified as slow oxidative (SO),
      fast oxidative-glycolytic (FOG), or fast glycolytic (FG), and fiber area and
      distribution were determined. At 113 and 154 d of age, R barrows had smaller (P <
      or = 0.04) SO fibers in the LM, STD, and STL, smaller (P < 0.01) FOG fibers in
      the STL, smaller (P = 0.03) FG fibers in the LM, and smaller (P < or = 0.04)
      overall mean area in the LM, STD, and STL. In the STL and RF, R barrows had fewer
      (P < or = 0.06) FG and more (P < or = 0.08) FOG fibers than A barrows at 113 and
      154 d of age. Except for smaller FOG fibers in the STD of R compared with A
      barrows slaughtered at the same BW, the myofiber size did not differ (P > or =
      0.11). However, the LM tended to have fewer (P = 0.06) SO and more (P < 0.01) FG
      fibers, and the STD had more (P < 0.01) FOG fibers in R barrows. Regardless of
      whether R barrows were slaughtered at the same age or the same BW as the A
      barrows, shear force values and cooking losses were greater (P < or = 0.08) in
      the STD and STL of R barrows. These findings revealed that myofiber hypertrophy
      was impaired by feed restriction in barrows compared at the same age, but
      differences in myofiber size vanished at the same BW. By contrast, restricted
      nutrient supply affected myofiber maturation depending on the age and BW, but the
      impact differed between muscles. The absence of changes in myofiber type
      distribution among the younger-lighter and older-heavier barrows indicated that
      myofiber maturation was already completed in the younger-lighter barrows.
      Although changes in meat quality traits were affected by the feeding regimen,
      they were not related to myofiber characteristics.

PMID- 17178815
TI  - Genetic correlations between two strains of Durocs and crossbreds from differing
      production environments for slaughter traits.
AB  - The aim of this study was to estimate the genetic correlations between 2 purebred
      Duroc pig populations (P1 and P2) and their terminal crossbreds [C1 = P1 x
      (Landrace x Large White) and C2 = P2 x (Landrace x Large White)] raised in
      different production environments. The traits analyzed were backfat (BF), muscle
      depth (MD), BW at slaughter (WGT), and weight per day of age (WDA). Data sets
      from P1, P2, C1, and C2 included 26,674, 8,266, 16,806, and 12,350 animals,
      respectively. Two-trait models (nucleus and commercial crossbreds) for each group
      included fixed (contemporary group, sex, weight, and age), random additive
      (animal for P1 and P2 and sire for C1 and C2), random litter, and random dam (C1
      and C2 only) effects. Heritability estimates (+/-SE) for BF were 0.46 +/- 0.04,
      0.38 +/- 0.02, 0.32 +/- 0.02, and 0.33 +/- 0.02 for P1, P2, C1, and C2,
      respectively. Heritability estimates for MD were 0.31 +/- 0.01, 0.23 +/- 0.02,
      0.19 +/- 0.01, and 0.12 +/- 0.01 for P1, P2, C1, and C2, respectively. The
      estimates for WGT and WDA were 0.31 +/- 0.01, 0.21 +/- 0.02, 0.16 +/- 0.01, and
      0.18 +/- 0.01 and 0.32 +/- 0.01, 0.22 +/- 0.02, 0.16 +/- 0.01, and 0.19 +/- 0.01,
      respectively. Genetic correlations between purebreds and crossbreds for BF were
      0.83 +/- 0.09 (P1 x C1) and 0.89 +/- 0.05 (P2 x C2), for MD 0.78 +/- 0.05 (P1 x
      C1) and 0.80 +/- 0.08 (P2 x C2). For WGT and WDA, the correlations were 0.53 +/-
      0.08 (P1 x C1), 0.80 +/- 0.10 (P2 x C2), and 0.60 +/- 0.07 (P1 x C1) and 0.79 +/-
      0.09 (P2 x C2), respectively. (Co)variances in crossbreds were adjusted to a live
      BW scale. Compared with purebreds, the genetic variances in crossbreds were
      lower, and the residual variances were greater. Sire variances in crossbreds were
      approximately 20 to 30% of the animal variances in purebreds for BF and MD but
      were 13 to 25% for WGT and WDA. The efficiency of purebred selection on
      crossbreds, assessed by EBV prediction weights, ranged from 0.43 to 0.91 for line
      1 and 0.70 to 0.92 for line 2. When nucleus and commercial environments differ
      substantially, the efficiency of selection varies by line and traits, and
      selection strategies that include crossbred data from typical production
      environments may therefore be desirable.

PMID- 17178816
TI  - Autonomic dysfunction in dementia.
AB  - BACKGROUND: There are no studies of autonomic function comparing Alzheimer's
      disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB) and
      Parkinson's disease dementia (PDD). AIMS: To assess cardiovascular autonomic
      function in 39 patients with AD, 30 with VAD, 30 with DLB, 40 with PDD and 38
      elderly controls by Ewing's battery of autonomic function tests and power
      spectral analysis of heart rate variability. To determine the prevalence of
      orthostatic hypotension and autonomic neuropathies by Ewing's classification.
      RESULTS: There were significant differences in severity of cardiovascular
      autonomic dysfunction between the four types of dementia. PDD and DLB had
      considerable dysfunction. VAD showed limited evidence of autonomic dysfunction
      and in AD, apart from orthostatic hypotension, autonomic functions were
      relatively unimpaired. PDD showed consistent impairment of both parasympathetic
      and sympathetic function tests in comparison with controls (all p<0.001) and AD
      (all p<0.03). DLB showed impairment of parasympathetic function (all p<0.05) and
      one of the sympathetic tests in comparison with controls (orthostasis; p = 0.02).
      PDD had significantly more impairment than DLB in some autonomic parameters
      (Valsalva ratio: p = 0.024; response to isometric exercise: p = 0.002). Patients
      with VAD showed impairment in two parasympathetic tests (orthostasis: p = 0.02;
      Valsalva ratio: p = 0.08) and one sympathetic test (orthostasis: p = 0.04). These
      results were in contrast with AD patients who only showed impairment in one
      sympathetic response (orthostasis: p = 0.004). The prevalence of orthostatic
      hypotension and autonomic neuropathies was higher in all dementias than in
      controls (all p<0.05). CONCLUSION: Autonomic dysfunction occurs in all common
      dementias but is especially prominent in PDD with important treatment
      implications.

PMID- 17178817
TI  - Levodopa slows prosaccades and improves antisaccades: an eye movement study in
      Parkinson's disease.
AB  - BACKGROUND: The integrity of frontal systems responsible for voluntary control
      and their interaction with subcortical regions involved in reflexive responses
      were studied in patients with Parkinson's disease (PD). Previous studies have
      shown that patients with PD have impaired executive function, including deficits
      in attention, motor planning and decision making. METHODS: Executive function was
      measured through eye movements: reflexive (stimulus driven) prosaccades and
      voluntary (internally guided) antisaccades. Patients with advanced idiopathic PD,
      off and on their optimal levodopa therapy, were tested on a prosaccade and an
      antisaccade task and compared with matched controls. RESULTS: Levodopa
      significantly increased response time for reflexive prosaccades and reduced error
      rate for voluntary antisaccades. CONCLUSIONS: Consistent with our proposed model,
      patients with PD in the medicated state are better able to plan and execute
      voluntary eye movements. These findings suggest levodopa improves function of the
      voluntary frontostriatal system, which is deficient in PD.

PMID- 17178818
TI  - The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy
      and other neurodegenerative diseases.
AB  - BACKGROUND: Progressive supranuclear palsy (PSP) is a progressive
      neurodegenerative disorder involving motor and cognitive dysfunction. Currently,
      there is no effective treatment either for symptomatic relief or disease
      modification. This relates, in part, to a lack of knowledge of the underlying
      neurochemical abnormalities, including cholinergic receptor status in the basal
      ganglia. AIM: To measure muscarinic M2 and M4 receptors in the basal ganglia in
      PSP. METHODS: The muscarinic M2 (presynaptic) and M4 (postsynaptic) receptors in
      the striatum, pallidum and adjacent insular cortex were autoradiographically
      measured in pathologically confirmed cases of PSP (n = 18), and compared with
      cases of Lewy body dementias (LBDs; n = 45), Alzheimer's disease (AD; n = 39) and
      controls (n = 50). RESULTS: In cases of PSP, there was a reduction in M2 and M4
      receptors in the posterior caudate and putamen compared to controls, but no
      significant changes in the pallidum. Cases with AD showed lower M2 receptors in
      the posterior striatum. Groups with LBD and AD showed higher M2 binding in the
      insular cortex compared with controls. CONCLUSIONS: The results suggest loss of
      posterior striatal cholinergic interneurones in PSP, and reduction in medium
      spiny projection neurones bearing M4 receptors. These results should be taken in
      the context of more widespread pathology in PSP, but may have implications for
      future trials of cholinergic treatments.

PMID- 17178819
TI  - Psychiatric disorders in preclinical Huntington's disease.
AB  - BACKGROUND: Psychiatric symptoms are a common feature of Huntington's disease
      (HD) and often precede the onset of motor and cognitive impairments. However, it
      remains unclear whether psychiatric changes in the preclinical period result from
      structural change, are a reaction to being at risk or simply a coincidental
      occurrence. Few studies have investigated the temporal course of psychiatric
      disorder across the preclinical period. OBJECTIVES: To compare lifetime and
      current prevalence of psychiatric disorder in presymptomatic gene carriers and
      non-carriers and to examine the relationship of psychiatric prevalence in gene
      carriers to temporal proximity of clinical onset. METHODS: Lifetime and current
      psychiatric histories of 204 at risk individuals (89 gene carriers and 115 non
      carriers) were obtained using a structured clinical interview, the Composite
      International Diagnostic Interview. Psychiatric disorders were classified using
      both standardised diagnostic criteria and a more subtle symptom based approach.
      Follow-up of gene carriers (n = 51) enabled analysis of the role of temporal
      proximity to clinical onset. RESULTS: Gene carriers and non-carriers did not
      differ in terms of the lifetime frequency of clinical psychiatric disorders or
      subclinical symptoms. However, gene carriers reported a significantly higher rate
      of current depressive symptoms. Moreover, the rate of depression increased as a
      function of proximity to clinical onset. CONCLUSIONS: Affective disorder is an
      important feature of the prodromal stages of HD. The findings indicate that
      depression cannot be accounted for by natural concerns of being at risk. There is
      evidence of a window of several years in which preclinical symptoms are apparent.

PMID- 17178820
TI  - Parkinson's disease and driving ability.
AB  - OBJECTIVES: To explore the driving problems associated with Parkinson's disease
      (PD) and to ascertain whether any clinical features or tests predict driver
      safety. METHODS: The driving ability of 154 individuals with PD referred to a
      driving assessment centre was determined by a combination of clinical tests,
      reaction times on a test rig and an in-car driving test. RESULTS: The majority of
      cases (104, 66%) were able to continue driving although 46 individuals required
      an automatic transmission and 10 others needed car modifications. Ability to
      drive was predicted by the severity of physical disease, age, presence of other
      associated medical conditions, particularly dementia, duration of disease, brake
      reaction, time on a test rig and score on a driving test (all p<0.001). The level
      of drug treatment and the length of driving history were not correlated.
      Discriminant analysis revealed that the most important features in distinguishing
      safety to drive were severe physical disease (Hoehn and Yahr stage 3), reaction
      time, moderate disease associated with another medical condition and high score
      on car testing. CONCLUSIONS: Most individuals with PD are safe to drive, although
      many benefit from car modifications or from using an automatic transmission. A
      combination of clinical tests and in-car driving assessment will establish safety
      to drive, and a number of clinical correlates can be shown to predict the likely
      outcome and may assist in the decision process. This is the largest series of
      consecutive patients seen at a driving assessment centre reported to date, and
      the first to devise a scoring system for on-road driving assessment.

PMID- 17178821
TI  - Intracranial fluid filled collection and superficial siderosis.

PMID- 17178822
TI  - Prospective comparison of acute confusion severity with duration of post
      traumatic amnesia in predicting employment outcome after traumatic brain injury.
AB  - BACKGROUND: Measurement of the duration of post-traumatic amnesia (PTA) is common
      practice, serving as an important index of the severity of traumatic brain injury
      (TBI) and a predictor of functional outcome. However, controversy exists
      regarding the nature of PTA; some studies indicate that it is a confusional state
      with symptoms that extend beyond disorientation and amnesia. OBJECTIVE: To
      evaluate the contribution of the severity of acute confusion 1 month after TBI to
      prediction of employment at 1 year after injury, comparing it with PTA duration.
      METHODS: Prospective study involving 171 participants with complete data, who met
      the study criteria, from 228 consecutive TBI Model System admissions. Outcome
      measures included weekly administration of the Delirium Rating Scale-Revised-98
      (DelRS-R98) to measure the severity of acute confusion. Evaluations closest to 1
      month after injury were used for study purposes. Duration of PTA was defined as
      the interval from injury until two consecutive Galveston Orientation and Amnesia
      Test scores of > or = 76 were obtained within a period of 24-72 h. Univariable
      and multivariable logistic regression were used to predict employment status at 1
      year after injury. RESULTS: Age, education and DelRS-R98 were significant
      predictors accounting for 34% of outcome variance. Individuals with greater
      confusion severity at 1 month after injury, older age and lower levels of
      education were less likely to be employed at 1 year after injury. Severity of
      confusion was more strongly associated with employment outcome (r(s) = -0.39)
      than was PTA duration (r(s) = -0.34). CONCLUSIONS: In addition to demographic
      indices, severity of acute confusion makes a unique contribution to predicting
      late outcome after TBI.

PMID- 17178823
TI  - Should patients participate in clinical decision making? An optimised balance
      block design controlled study of goal setting in a rehabilitation unit.
AB  - OBJECTIVES: The recent National Service Framework for Long Term Conditions
      recommends that patients participate more in decision making about their care.
      However, few protocols exist to support this. One potentially useful method is
      goal setting, but little has been done to evaluate the added value of increasing
      patient participation in this way. Therefore, this study examined the impact of
      an increased participation goal setting protocol in a neurorehabilitation
      setting. DESIGN: The study was an AB optimised balance block design with each
      block lasting 3 months, over an 18 month period. SETTING AND PARTICIPANTS:
      Patients (n = 201) were recruited from an inpatient neurological rehabilitation
      unit. INTERVENTIONS: Patients (n = 100) recruited in phase A were involved in
      "usual practice" goal setting. Patients (n = 101) recruited in phase B were
      involved in "increased participation" goal setting, which included a protocol to
      help them define and prioritise their own goals. MAIN OUTCOME MEASURES: Patients'
      perceptions of the relevance of goal setting and their autonomy within the
      process; the number, type and outcome of goals; and level of functional ability.
      RESULTS: Phase B patients ("increased participation") set fewer goals, of which
      significantly more were participation related. These patients perceived the goals
      to be more relevant, and expressed greater autonomy and satisfaction with goal
      setting. There were no differences in functional outcomes between the groups.
      CONCLUSION: This study has shown that patients prefer increased participation in
      the goal setting process over standard procedures, perceiving their goals as more
      relevant and rehabilitation more patient centred despite the absence of
      functional gains. Effective patient centred care can be realised by using
      structures that help support patients to identify and communicate their
      priorities. As such, our findings suggest patients would benefit from greater
      participation in this aspect of clinical decision making.

PMID- 17178824
TI  - Trunk performance after stroke: an eye catching predictor of functional outcome.
AB  - BACKGROUND AND AIMS: Trunk performance is an important predictor of functional
      outcome after stroke. However, the percentage of explained variance varies
      considerably between studies. This may be explained by the stroke population
      examined, the different scales used to assess trunk performance and the time
      points used to measure outcome. The aim of this multicentre study was to examine
      the predictive validity of the Trunk Impairment Scale (TIS) and its subscales
      when predicting the Barthel Index score at 6 months after stroke. METHODS: A
      total of 102 subjects were recruited in three European rehabilitation centres.
      Participants were assessed on admission (median time since stroke onset 20 days)
      and 6 months after stroke. Correlation analysis and forward stepwise multiple
      regression analysis were used to model outcome. RESULTS: The best predictors of
      the Barthel Index scores at 6 months after stroke were total TIS score (partial
      R2 = 0.52, p<.0001) and static sitting balance subscale score (partial R2 = 0.50,
      p<.0001) on admission. The TIS score on admission and its static sitting balance
      subscale were stronger predictors of the Barthel Index score at 6 months than the
      Barthel Index score itself on admission. CONCLUSIONS: This study emphasises the
      importance of trunk performance, especially static sitting balance, when
      predicting functional outcome after stroke. The TIS is recommended as a
      prediction instrument in the rehabilitation setting when considering the
      prognosis of stroke patients. Future studies should address the evolution of
      trunk performance over time and the evaluation of treatment interventions to
      improve trunk performance.

PMID- 17178825
TI  - Improvement of quality of life in patients surgically treated for asymptomatic
      unruptured intracranial aneurysms.
AB  - OBJECTIVE: To compare the preoperative and postoperative health-related quality
      of life (QOL) and psychological state of patients with asymptomatic unruptured
      intracranial aneurysms (ICAs) who underwent elective surgery. METHODS: Out of 67
      patients who underwent neck clipping of ICAs, we assessed the QOL of 61 patients
      using Short Form-36 (SF-36); their psychological state was rated on the Hospital
      Anxiety and Depression Scale (HADS) before, 3 months, and 1 and 3 years after
      treatment. RESULTS: The preoperative mean scores for each of the eight SF-36
      domains except bodily pain were significantly lower in the study population than
      in the reference population. 14 (20.9%) patients experienced surgical
      complications defined as neurological deterioration and/or abnormal CT findings
      within 30 days of the operation. Despite some complications, the QOL of all
      operated patients returned to the mean level of the reference population 3 years
      after treatment. At 3 months after surgery, the scores for psychosocial
      activities and general health perception were transiently below the preoperative
      levels. According to the HADS, the patients experienced mild anxiety before the
      operation; it disappeared by the third postoperative month. CONCLUSIONS:
      Preoperatively, patients with unruptured ICAs reported a significantly decreased
      QOL. It further declined transiently after elective surgery, but it returned to
      the mean level recorded for the reference population within 3 years. Our findings
      suggest that these patients derived significant QOL benefits from their surgery.
      Hence subjective QOL issues should be considered in deciding whether treatment
      related risks and their natural history, such as their potential rupture, warrant
      surgery of asymptomatic unruptured ICAs.

PMID- 17178826
TI  - A review of screening tests for cognitive impairment.
AB  - The merit of screening for dementia and cognitive impairment has been the subject
      of recent debate. One of the main limitations in this regard is the lack of
      robust evidence to support the many screening tests available. Although plentiful
      in number, few such instruments have been well validated in the populations for
      which they are intended to be used. In addition, it is likely that "one size does
      not fit all" in cognitive screening, leading to the development of many
      specialised tests for particular types of impairment. In this review, we sought
      to ascertain the number of screening tools currently available, and to examine
      the evidence for their validity in detecting different diagnoses in a variety of
      populations. A further consideration was whether each screen elicited indices of
      a range of cognitive, affective and functional domains or abilities, as such
      information is a valuable adjunct to simple cut-off scores. Thirty-nine screens
      were identified and discussed with reference to three purposes: brief assessment
      in the doctor's office; large scale community screening programmes; and
      identifying profiles of impairment across different cognitive, psychiatric and
      functional domains/abilities, to guide differential diagnosis and further
      assessment. A small number of screens rated highly for both validity and content.
      This review is intended to serve as an evaluative resource, to guide clinicians
      and researchers in choosing among the wide range of screens which are currently
      available.

PMID- 17178827
TI  - BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of
      endoplasmic reticulum stress transducer.
AB  - Endoplasmic reticulum (ER) stress transducers IRE1 (inositol requiring 1), PERK
      (PKR-like endoplasmic reticulum kinase), and ATF6 (activating transcription
      factor 6) are well known to transduce signals from the ER to the cytoplasm and
      nucleus when unfolded proteins accumulate in the ER. Recently, we identified
      OASIS (old astrocyte specifically induced substance) as a novel ER stress
      transducer expressed in astrocytes. We report here that BBF2H7 (BBF2 human
      homolog on chromosome 7), an ER-resident transmembrane protein with the bZIP
      domain in the cytoplasmic portion and structurally homologous to OASIS, is
      cleaved at the membrane in response to ER stress. The cleaved fragments of BBF2H7
      translocate into the nucleus and can bind directly to cyclic AMP-responsive
      element sites to activate transcription of target genes. Interestingly, although
      BBF2H7 protein is not expressed under normal conditions, it is markedly induced
      at the translational level during ER stress, suggesting that BBF2H7 might
      contribute to only the late phase of unfolded protein response signaling. In a
      mouse model of focal brain ischemia, BBF2H7 protein is prominently induced in
      neurons in the peri-infarction region. Furthermore, in a neuroblastoma cell line,
      BBF2H7 overexpression suppresses ER stress-induced cell death, while small
      interfering RNA knockdown of BBF2H7 promotes ER stress-induced cell death. Taken
      together, our results suggest that BBF2H7 is a novel ER stress transducer and
      could play important roles in preventing accumulation of unfolded proteins in
      damaged neurons.

PMID- 17178828
TI  - Requirement of Nhp6 proteins for transcription of a subset of tRNA genes and
      heterochromatin barrier function in Saccharomyces cerevisiae.
AB  - A key event in tRNA gene (tDNA) transcription by RNA polymerase (Pol) III is the
      TFIIIC-dependent assembly of TFIIIB upstream of the transcription start site.
      Different tDNA upstream sequences bind TFIIIB with different affinities, thereby
      modulating tDNA transcription. We found that in the absence of Nhp6 proteins, the
      influence of the 5'-flanking region on tRNA gene transcription is dramatically
      enhanced in Saccharomyces cerevisiae. Expression of a tDNA bearing a suboptimal
      TFIIIB binding site, but not of a tDNA preceded by a strong TFIIIB binding
      region, was strongly dependent on Nhp6 in vivo. Upstream sequence-dependent
      stimulation of tRNA gene transcription by Nhp6 could be reproduced in vitro, and
      Nhp6 proteins were found associated with tRNA genes in yeast cells. We also show
      that both transcription and silencing barrier activity of a tDNA(Thr) at the HMR
      locus are compromised in the absence of Nhp6. Our data suggest that Nhp6 proteins
      are important components of Pol III chromatin templates that contribute both to
      the robustness of tRNA gene expression and to positional effects of Pol III
      transcription complexes.

PMID- 17178829
TI  - LRIG1 is a novel negative regulator of the Met receptor and opposes Met and Her2
      synergy.
AB  - The Met receptor tyrosine kinase regulates a complex array of cellular behaviors
      collectively known as "invasive growth." While essential for normal development
      and wound repair, this program is frequently co-opted by tumors to promote their
      own growth, motility, and invasion. Met is overexpressed in a variety of human
      tumors, and this aberrant expression correlates with poor patient prognosis.
      Previous studies indicate that Met receptor levels are governed in part by cbl
      mediated ubiquitination and degradation, and uncoupling of Met from cbl-mediated
      ubiquitination promotes its transforming activity. Here we describe a novel
      mechanism for Met degradation. We find that the Met receptor interacts with the
      transmembrane protein LRIG1 independent of hepatocyte growth factor (HGF)
      stimulation and that LRIG1 destabilizes the Met receptor in a cbl-independent
      manner. Overexpression of LRIG1 destabilizes endogenous Met receptor in breast
      cancer cells and impairs their ability to respond to HGF. LRIG1 knockdown
      increases Met receptor half-life, indicating that it plays an essential role in
      Met degradation. Finally, LRIG1 opposes Met synergy with the ErbB2/Her2 receptor
      tyrosine kinase in driving cellular invasion. We conclude that LRIG1 is a novel
      suppressor of Met function, serving to regulate cellular receptor levels by
      promoting Met degradation in a ligand- and cbl-independent manner.

PMID- 17178830
TI  - An unconventional human Ccr4-Caf1 deadenylase complex in nuclear cajal bodies.
AB  - mRNA deadenylation is a key process in the regulation of translation and mRNA
      turnover. In Saccharomyces cerevisiae, deadenylation is primarily carried out by
      the Ccr4p and Caf1p/Pop2p subunits of the Ccr4-Not complex, which is conserved in
      eukaryotes including humans. Here we have identified an unconventional human Ccr4
      Caf1 complex containing hCcr4d and hCaf1z, distant human homologs of yeast Ccr4p
      and Caf1p/Pop2p, respectively. The hCcr4d-hCaf1z complex differs from
      conventional Ccr4-Not deadenylase complexes, because (i) hCaf1z and hCcr4d
      concentrate in nuclear Cajal bodies and shuttle between the nucleus and cytoplasm
      and (ii) the hCaf1z subunit, in addition to rapid deadenylation, subjects
      substrate RNAs to slow exonucleolytic degradation from the 3' end in vitro.
      Exogenously expressed hCaf1z shows both of those activities on reporter mRNAs in
      human HeLa cells and stimulates general mRNA decay when restricted to the
      cytoplasm by deletion of its nuclear localization signal. These observations
      suggest that the hCcr4d-hCaf1z complex may function either in the nucleus or in
      the cytoplasm after its nuclear export, to degrade polyadenylated RNAs, such as
      mRNAs, pre-mRNAs, or those RNAs that are polyadenylated prior to their
      degradation in the nucleus.

PMID- 17178831
TI  - Regulation of EphA8 gene expression by TALE homeobox transcription factors during
      development of the mesencephalon.
AB  - The mouse ephA8 gene is expressed in a rostral-to-caudal gradient in the
      developing superior colliculus, and these EphA gradients may contribute to the
      proper development of the retinocollicular projection. Thus, it is of
      considerable interest to elucidate how the ephA8 gene expression is controlled by
      upstream regulators during the development of the mesencephalon. In this study,
      we employed in vivo expression analysis in transgenic mouse embryos to dissect
      the cis-acting DNA regulatory region, leading to the identification of a CGGTCA
      sequence critical for the ephA8 enhancer activity. Using this element as the
      target in a yeast one-hybrid system, we identified a Meis homeobox transcription
      factor. Significantly, DNA binding sites for Pbx, another TALE homeobox
      transcription factor, were also identified in the ephA8 enhancer region. Meis2
      and Pbx1/2 are specifically expressed in the entire region of the dorsal
      mesencephalon, where specific colocalization of EphA8 and Meis is restricted to a
      subset of cells. Meis2 and Pbx2 synergistically bind the ephA8 regulatory
      sequence in vitro, and this interaction is critical for the transcriptional
      activation of a reporter construct bearing the ephA8 regulatory region in the
      presence of histone deacetylase inhibitor. More importantly, when expressed in
      the embryonic midbrain, the dominant-negative form of Meis down-regulates
      endogenous ephA8. Interestingly, we found that both Meis2 and Pbx2 are
      constitutively bound in the ephA8 regulatory region in the dorsal mesencephalon.
      These studies strongly suggest that Meis and Pbx homeobox transcription factors
      tightly associate with the ephA8 regulatory sequence and require an additional
      unidentified regulator to ensure the specific activation of ephA8.

PMID- 17178832
TI  - Dimerization of protein tyrosine phosphatase sigma governs both ligand binding
      and isoform specificity.
AB  - Signaling through receptor protein tyrosine phosphatases (RPTPs) can influence
      diverse processes, including axon development, lymphocyte activation, and cell
      motility. The molecular regulation of these enzymes, however, is still poorly
      understood. In particular, it is not known if, or how, the dimerization state of
      RPTPs is related to the binding of extracellular ligands. Protein tyrosine
      phosphatase sigma (PTPsigma) is an RPTP with major isoforms that differ in their
      complements of fibronectin type III domains and in their ligand-binding
      specificities. In this study, we show that PTPsigma forms homodimers in the cell,
      interacting at least in part through the transmembrane region. Using this
      knowledge, we provide the first evidence that PTPsigma ectodomains must be
      presented as dimers in order to bind heterophilic ligands. We also provide
      evidence of how alternative use of fibronectin type III domain complements in two
      major isoforms of PTPsigma can alter the ligand binding specificities of PTPsigma
      ectodomains. The data suggest that the alternative domains function largely to
      change the rotational conformations of the amino-terminal ligand binding sites of
      the ectodomain dimers, thus imparting novel ligand binding properties. These
      findings have important implications for our understanding of how heterophilic
      ligands interact with, and potentially regulate, RPTPs.

PMID- 17178833
TI  - Sleeping beauty transposase has an affinity for heterochromatin conformation.
AB  - The Sleeping Beauty (SB) transposase reconstructed from salmonid fish has high
      transposition activity in mammals and has been a useful tool for insertional
      mutagenesis and gene delivery. However, the transposition efficiency has varied
      significantly among studies. Our previous study demonstrated that the
      introduction of methylation into the SB transposon enhanced transposition,
      suggesting that transposition efficiency is influenced by the epigenetic status
      of the transposon region. Here, we examined the influence of the chromatin status
      on SB transposition in mouse embryonic stem cells. Heterochromatin conformation
      was introduced into the SB transposon by using a tetracycline-controlled
      transrepressor (tTR) protein, consisting of a tetracycline repressor (TetR) fused
      to the Kruppel-associated box (KRAB) domain of human KOX1 through tetracycline
      operator (tetO) sequences. The excision frequency of the SB transposon, which is
      the first step of the transposition event, was enhanced by approximately 100
      fold. SB transposase was found to be colocalized with intense DAPI (4',6'
      diamidino-2-phenylindole) staining and with the HP1 family by biochemical
      fractionation analyses. Furthermore, chromatin immunoprecipitation analysis
      revealed that SB transposase was recruited to tTR-induced heterochromatic
      regions. These data suggest that the high affinity of SB transposase for
      heterochromatin conformation leads to enhancement of SB transposition efficiency.

PMID- 17178834
TI  - Improper organization of the actin cytoskeleton affects protein synthesis at
      initiation.
AB  - Although the actin cytoskeleton and the translation machinery are considered to
      be separate cellular complexes, growing evidence supports overlapping regulation
      of the two systems. Because of its interaction with actin, the eukaryotic
      translation elongation factor 1A (eEF1A) is proposed to be a regulator or link
      between these processes. Using a genetic approach with the yeast Saccharomyces
      cerevisiae, specific regions of eEF1A responsible for actin interactions and
      bundling were identified. Five new mutations were identified along one face of
      eEF1A. Dramatic changes in cell growth, cell morphology, and actin cable and
      patch formation as well as a unique effect on total translation in strains
      expressing the F308L or S405P eEF1A mutant form were observed. The translation
      effects do not correlate with reduced translation elongation but instead include
      an initiation defect. Biochemical analysis of the eEF1A mutant forms demonstrated
      reduced actin-bundling activity in vitro. Reduced total translation and/or the
      accumulation of 80S ribosomes in strains with either a mutation or a null allele
      of genes encoding actin itself or actin-regulating proteins Tpm1p, Mdm20p, and
      Bnirp/Bni1p was observed. Our data demonstrate that eEF1A, other actin binding
      proteins, and actin mutants affect translation initiation through the actin
      cytoskeleton.

PMID- 17178835
TI  - Neuropilin-1 is a direct target of the transcription factor E2F1 during cerebral
      ischemia-induced neuronal death in vivo.
AB  - The nuclear transcription factor E2F1 plays an important role in modulating
      neuronal death in response to excitotoxicity and cerebral ischemia. Here, by
      comparing gene expression in brain cortices from E2F1(+/+) and E2F1(-/-) mice
      using a custom high-density DNA microarray, we identified a group of putative
      E2F1 target genes that might be responsible for ischemia-induced E2F1-dependent
      neuronal death. Neuropilin 1 (NRP-1), a receptor for semaphorin 3A-mediated axon
      growth cone collapse and retraction, was confirmed to be a direct target of E2F1
      based on (i) the fact that the NRP-1 promoter sequence contains an E2F1 binding
      site, (ii) reactivation of NRP-1 expression in E2F1(-/-) neurons when the E2F1
      gene was replaced, (iii) activation of the NRP-1 promoter by E2F1 in a luciferase
      reporter assay, (iv) electrophoretic mobility gel shift analysis confirmation of
      the presence of an E2F binding sequence in the NRP-1 promoter, and (v) the fact
      that a chromatin immunoprecipitation assay showed that E2F1 binds directly to the
      endogenous NRP-1 promoter. Interestingly, the temporal induction in cerebral
      ischemia-induced E2F1 binding to the NRP-1 promoter correlated with the temporal
      induction profile of NRP-1 mRNA, confirming that E2F1 positively regulates NRP-1
      during cerebral ischemia. Functional analysis also showed that NRP-1 receptor
      expression was extremely low in E2F1(-/-) neurons, which led to the diminished
      response to semaphorin 3A-induced axonal shortening and neuronal death. An NRP-1
      selective peptide inhibitor provided neuroprotection against oxygen-glucose
      deprivation. Taken together, these findings support a model in which E2F1 targets
      NRP-1 to modulate axonal damage and neuronal death in response to cerebral
      ischemia.

PMID- 17178838
TI  - Extracellular pH dynamically controls cell surface delivery of functional TRPV5
      channels.
AB  - Extracellular pH has long been known to affect the rate and magnitude of ion
      transport processes among others via regulation of ion channel activity. The
      Ca(2+)-selective transient receptor potential vanilloid 5 (TRPV5) channel
      constitutes the apical entry gate in Ca(2+)-transporting cells, contributing
      significantly to the overall Ca(2+) balance. Here, we demonstrate that
      extracellular pH determines the cell surface expression of TRPV5 via a unique
      mechanism. By a comprehensive approach using total internal reflection
      fluorescence microscopy, cell surface protein labeling, electrophysiology,
      (45)Ca(2+) uptake assays, and functional channel recovery after chemobleaching,
      this study shows that upon extracellular alkalinization, a pool of TRPV5
      containing vesicles is rapidly recruited to the cell surface without collapsing
      into the plasma membrane. These vesicles contain functional TRPV5 channels since
      extracellular alkalinization is accompanied by increased TRPV5 activity.
      Conversely, upon subsequent extracellular acidification, vesicles are retrieved
      from the plasma membrane, simultaneously resulting in decreased TRPV5 activity.
      Thus, TRPV5 accesses the extracellular compartment via transient openings of
      vesicles, suggesting that rapid responses of constitutive active TRP channels to
      physiological stimuli rely on vesicular "kiss and linger" interactions with the
      plasma membrane.

PMID- 17178836
TI  - Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated
      degradation.
AB  - The dbl proto-oncogene product is a prototype of a growing family of guanine
      nucleotide exchange factors (GEFs) that stimulate the activation of small GTP
      binding proteins from the Rho family. Mutations that result in the loss of proto
      Dbl's amino terminus produce a variant with constitutive GEF activity and high
      oncogenic potential. Here, we show that proto-Dbl is a short-lived protein that
      is kept at low levels in cells by efficient ubiquitination and degradation. The
      cellular fate of proto-Dbl is regulated by interactions with the chaperones Hsc70
      and Hsp90 and the protein-ubiquitin ligase CHIP, and these interactions are
      mediated by the spectrin domain of proto-Dbl. We show that CHIP is the E3 ligase
      responsible for ubiquitination and proteasomal degradation of proto-Dbl, while
      Hsp90 functions to stabilize the protein. Onco-Dbl, lacking the spectrin homology
      domain, cannot bind these regulators and therefore accumulates in cells at high
      levels, leading to persistent stimulation of its downstream signaling pathways.

PMID- 17178839
TI  - Fission yeast Cut8 is required for the repair of DNA double-strand breaks,
      ribosomal DNA maintenance, and cell survival in the absence of Rqh1 helicase.
AB  - Schizosaccharomyces pombe Rqh1 is a member of the RecQ DNA helicase family.
      Members of this protein family are mutated in cancer predisposition diseases,
      causing Bloom's, Werner, and Rothmund-Thomson syndromes. Rqh1 forms a complex
      with topoisomerase III and is proposed to process or disrupt aberrant
      recombination structures that arise during S phase to allow proper chromosome
      segregation during mitosis. Intriguingly, in the absence of Rqh1, processing of
      these structures appears to be dependent on Rad3 (human ATR) in a manner that is
      distinct from its role in checkpoint control. Here, we show that rad3 rqh1
      mutants are normally committed to a lethal pathway of DNA repair requiring
      homologous recombination, but blocking this pathway by Rhp51 inactivation
      restores viability. Remarkably, viability is also restored by overexpression of
      Cut8, a nuclear envelope protein involved in tethering and proper function of the
      proteasome. In keeping with a recently described function of the proteasome in
      the repair of DNA double-strand breaks, we found that Cut8 is also required for
      DNA double-strand break repair and is essential for proper chromosome segregation
      in the absence of Rqh1, suggesting that these proteins might function in a common
      pathway in homologous recombination repair to ensure accurate nuclear division in
      S. pombe.

PMID- 17178837
TI  - RSC mobilizes nucleosomes to improve accessibility of repair machinery to the
      damaged chromatin.
AB  - Repair of DNA double-strand breaks (DSBs) protects cells and organisms, as well
      as their genome integrity. Since DSB repair occurs in the context of chromatin,
      chromatin must be modified to prevent it from inhibiting DSB repair. Evidence
      supports the role of histone modifications and ATP-dependent chromatin remodeling
      in repair and signaling of chromosome DSBs. The key questions are, then, what the
      nature of chromatin altered by DSBs is and how remodeling of chromatin
      facilitates DSB repair. Here we report a chromatin alteration caused by a single
      HO endonuclease-generated DSB at the Saccharomyces cerevisiae MAT locus. The
      break induces rapid nucleosome migration to form histone-free DNA of a few
      hundred base pairs immediately adjacent to the break. The DSB-induced nucleosome
      repositioning appears independent of end processing, since it still occurs when
      the 5'-to-3' degradation of the DNA end is markedly reduced. The tetracycline
      controlled depletion of Sth1, the ATPase of RSC, or deletion of RSC2 severely
      reduces chromatin remodeling and loading of Mre11 and Yku proteins at the DSB.
      Depletion of Sth1 also reduces phosphorylation of H2A, processing, and joining of
      DSBs. We propose that RSC-mediated chromatin remodeling at the DSB prepares
      chromatin to allow repair machinery to access the break and is vital for
      efficient DSB repair.

PMID- 17178840
TI  - Deciphering the cross talk between hnRNP K and c-Src: the c-Src activation domain
      in hnRNP K is distinct from a second interaction site.
AB  - The protein tyrosine kinase c-Src is regulated by two intramolecular
      interactions. The repressed state is achieved through the interaction of the Src
      homology 2 (SH2) domain with the phosphorylated C-terminal tail and the
      association of the SH3 domain with a polyproline type II helix formed by the
      linker region between SH2 and the kinase domain. hnRNP K, the founding member of
      the KH domain protein family, is involved in chromatin remodeling, regulation of
      transcription, and translation of specific mRNAs and is a target in different
      signal transduction pathways. In particular, it functions as a specific activator
      and a substrate of the tyrosine kinase c-Src. Here we address the question how
      hnRNP K interacts with and activates c-Src. We define the proline residues in
      hnRNP K in the proline-rich motifs P2 (amino acids [aa] 285 to 297) and P3 (aa
      303 to 318), which are necessary and sufficient for the specific activation of c
      Src, and we dissect the amino acid sequence (aa 216 to 226) of hnRNP K that
      mediates a second interaction with c-Src. Our findings indicate that the
      interaction with c-Src and the activation of the kinase are separable functions
      of hnRNP K. hnRNP K acts as a scaffold protein that integrates signaling cascades
      by facilitating the cross talk between kinases and factors that mediate nucleic
      acid-directed processes.

PMID- 17178842
TI  - Quantitating therapeutic disruption of tumor blood flow with intravital video
      microscopy.
AB  - Vascular-disrupting agents (VDA) kill tumor cells by selectively disrupting blood
      circulation in tumors. In vivo analysis of this intensely studied class of
      anticancer agents is invaluable for preclinical assessment of pharmacodynamic end
      points and effective therapeutic windows. In this review, we consider the role of
      intravital video microscopy in measuring tumor vascular response to VDAs, the
      potential of which lies in the opportunity to quantitate specific variables and
      to obtain real-time information on how VDAs affect tumor microcirculation.

PMID- 17178841
TI  - Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell
      adhesion and growth.
AB  - ALR (MLL2) is a member of the human MLL family, which belongs to a larger SET1
      family of histone methyltransferases. We found that ALR is present within a
      stable multiprotein complex containing a cohort of proteins shared with other
      SET1 family complexes and several unique components, such as PTIP and the jumonji
      family member UTX. Like other complexes formed by SET1 family members, the ALR
      complex exhibited strong H3K4 methyltransferase activity, conferred by the ALR
      SET domain. By generating ALR knockdown cell lines and comparing their expression
      profiles to that of control cells, we identified a set of genes whose expression
      is activated by ALR. Some of these genes were identified by chromatin
      immunoprecipitation as direct ALR targets. The ALR complex was found to associate
      in an ALR-dependent fashion with promoters and transcription initiation sites of
      target genes and to induce H3K4 trimethylation. The most characteristic features
      of the ALR knockdown cells were changes in the dynamics and mode of cell
      spreading/polarization, reduced migration capacity, impaired anchorage-dependent
      and -independent growth, and decreased tumorigenicity in mice. Taken together,
      our results suggest that ALR is a transcriptional activator that induces the
      transcription of target genes by covalent histone modification. ALR appears to be
      involved in the regulation of adhesion-related cytoskeletal events, which might
      affect cell growth and survival.

PMID- 17178843
TI  - Pathophysiologic effects of vascular-targeting agents and the implications for
      combination with conventional therapies.
AB  - A functional vascular supply is critical for the continued growth and development
      of solid tumors. It also plays a major role in metastatic spread of tumor cells.
      This importance has led to the concept of targeting the vasculature of the tumor
      as a form of cancer therapy. Two major types of vascular-targeting agent (VTA)
      have now emerged: those that prevent the angiogenic development of the
      neovasculature of the tumor and those that specifically damage the already
      established tumor vascular supply. When used alone neither approach readily leads
      to tumor control, and so, for VTAs to be most successful in the clinic they will
      need to be combined with more conventional therapies. However, by affecting the
      tumor vascular supply, these VTAs should induce pathophysiologic changes in
      variables, such as blood flow, pH, and oxygenation. Such changes could have
      negative or positive influences on the tumor response to more conventional
      therapies. This review aims to discuss the pathophysiologic changes induced by
      VTAs and the implications of these effects on the potential use of VTAs in
      combined modality therapy.

PMID- 17178844
TI  - Ataxia telangiectasia mutated down-regulates phospho-extracellular signal
      regulated kinase 1/2 via activation of MKP-1 in response to radiation.
AB  - Ataxia telangiectasia mutated (ATM) kinase plays a crucial role in the cellular
      response to DNA damage and in radiation resistance. Although much effort has
      focused on the relationship between ATM and other nuclear signal transducers,
      little is known about interactions between ATM and mitogenic signaling pathways.
      In this study, we show a novel relationship between ATM kinase and extracellular
      signal-regulated kinase 1/2 (ERK1/2), a key mitogenic stimulator. Activation of
      ATM by radiation down-regulates phospho-ERK1/2 and its downstream signaling via
      increased expression of mitogen-activated protein kinase phosphatase MKP-1 in
      both cell culture and tumor models. This dephosphorylation of ERK1/2 is
      independent of epidermal growth factor receptor (EGFR) activity and is associated
      with radioresistance. These findings show a new function for ATM in the control
      of mitogenic pathways affecting cell signaling and emphasize the key role of ATM
      in coordinating the cellular response to DNA damage.

PMID- 17178845
TI  - SLC5A8 triggers tumor cell apoptosis through pyruvate-dependent inhibition of
      histone deacetylases.
AB  - Tumor cells up-regulate glycolysis but convert pyruvate into lactate instead of
      oxidizing it. Here, we show that pyruvate, but not lactate, is an inhibitor of
      histone deacetylases (HDAC) and an inducer of apoptosis in tumor cells and that
      SLC5A8, a Na(+)/monocarboxylate cotransporter, is obligatory for this process. We
      found that SLC5A8 is expressed in nontransformed breast epithelial cell lines but
      silenced by DNA methylation in tumor cell lines. The down-regulation of the gene
      is also evident in primary breast tumors. When MCF7 breast tumor cells are
      transfected with SLC5A8 cDNA, the cells undergo pyruvate-dependent apoptosis.
      Butyrate and propionate also induce apoptosis in SLC5A8-expressing cells, whereas
      lactate does not. The differential ability of these monocarboxylates to cause
      apoptosis in SLC5A8-expressing MCF7 cells correlates with their ability to
      inhibit HDACs. Apoptosis induced by SLC5A8/pyruvate in MCF7 cells is associated
      with up-regulation of p53, Bax, tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL), TRAIL receptor (TRAILR) 1, and TRAILR2 and down-regulation of
      Bcl2 and survivin. Lactate dehydrogenase isozymes are differentially expressed in
      nontransformed cells and tumor cells such that the latter convert pyruvate into
      lactate. Silencing of SLC5A8 coupled with conversion of pyruvate into lactate in
      tumor cells correlates with increased HDAC activity in these cells compared with
      nontransformed cells. Our studies thus identify pyruvate as a HDAC inhibitor and
      indicate that the Na(+)-coupled pyruvate transport underlies the tumor
      suppressive role of SLC5A8. We propose that tumor cells silence SLC5A8 and
      convert pyruvate into lactate as complementary mechanisms to avoid pyruvate
      induced cell death.

PMID- 17178846
TI  - Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular
      transformation.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important inflammation cytokine
      without known direct effect on DNA. In this study, we found that TNF-alpha can
      cause DNA damages through reactive oxygen species. The mutagenic effect of TNF
      alpha is comparable with that of ionizing radiation. TNF-alpha treatment in
      cultured cells resulted in increased gene mutations, gene amplification,
      micronuclei formation, and chromosomal instability. Antioxidants significantly
      reduced TNF-alpha-induced genetic damage. TNF-alpha also induced oxidative stress
      and nucleotide damages in mouse tissues in vivo. Moreover, TNF-alpha treatment
      alone led to increased malignant transformation of mouse embryo fibroblasts,
      which could be partially suppressed by antioxidants. As TNF-alpha is involved in
      chronic inflammatory diseases, such as chronic hepatitis, ulcerative colitis, and
      chronic skin ulcers, and these diseases predispose the patients to cancer
      development, our results suggest a novel pathway through which TNF-alpha promotes
      cancer development through induction of gene mutations, in addition to the
      previously reported mechanisms, in which nuclear factor-kappaB activation was
      implicated.

PMID- 17178847
TI  - Adrenal hyperplasia and adenomas are associated with inhibition of
      phosphodiesterase 11A in carriers of PDE11A sequence variants that are frequent
      in the population.
AB  - Several types of adrenocortical tumors that lead to Cushing syndrome may be
      caused by aberrant cyclic AMP (cAMP) signaling. We recently identified patients
      with micronodular adrenocortical hyperplasia who were carriers of inactivating
      mutations in the 2q-located phosphodiesterase 11A (PDE11A) gene. We now studied
      the frequency of two missense substitutions, R804H and R867G, in conserved
      regions of the enzyme in several sets of normal controls, including 745
      individuals enrolled in a longitudinal cohort study, the New York Cancer Project.
      In the latter, we also screened for the presence of the previously identified
      PDE11A nonsense mutations. R804H and R867G were frequent among patients with
      adrenocortical tumors; although statistical significance was not reached, these
      variants affected significantly enzymatic function in vitro with variable
      increases in cAMP and/or cyclic guanosine 3',5'-monophosphate levels in HeLa and
      HEK293 cells. Adrenocortical tissues carrying the R804H mutation showed 2q
      allelic losses and higher cyclic nucleotide levels and cAMP-responsive element
      binding protein phosphorylation. We conclude that missense mutations of the
      PDE11A gene that affect enzymatic activity in vitro are present in the general
      population; protein-truncating PDE11A mutations may also contribute to a
      predisposition to other tumors, in addition to their association with
      adrenocortical hyperplasia. We speculate that PDE11A genetic defects may be
      associated with adrenal pathology in a wider than previously suspected clinical
      spectrum that includes asymptomatic individuals.

PMID- 17178848
TI  - Activated checkpoint kinase 2 provides a survival signal for tumor cells.
AB  - Tumor cells often become resistant to DNA damage-based therapy; however, the
      underlying mechanisms are not yet understood. Here, we show that tumor cells
      exposed to DNA damage counteract cell death by releasing the antiapoptotic
      protein, survivin, from mitochondria. This is independent of p53, and requires
      activated checkpoint kinase 2 (Chk2), a putative tumor suppressor. Molecular or
      genetic targeting of Chk2 prevents the release of survivin from mitochondria,
      enhances DNA damage-induced tumor cell apoptosis, and inhibits the growth of
      resistant in vivo tumors. Therefore, activated Chk2 circumvents its own tumor
      suppressive functions by promoting tumor cell survival. Inhibiting Chk2 in
      combination with DNA-damaging agents may provide a rational approach for treating
      resistant tumors.

PMID- 17178849
TI  - Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium
      induced colitis.
AB  - Inflammatory bowel diseases, chronic inflammatory disorders, have been strongly
      linked with an increased risk of the development of colorectal cancer.
      Understanding the etiology of these diseases is pivotal for the improvement of
      currently available strategies to fight against inflammatory bowel disease, and
      more importantly, to prevent colorectal cancer. Nuclear factor-erythroid 2
      related factor 2 (Nrf2) has been known to be a transcriptional factor which plays
      a crucial role in cytoprotection against inflammation, as well as oxidative and
      electrophilic stresses. The aim of this study is to investigate the role of Nrf2
      in the regulation of dextran sulfate sodium (DSS)-induced experimental colitis in
      mice. Nrf2-deficient mice were found to be more susceptible to DSS-induced
      colitis as shown by the increased severity of colitis following 1 week of oral
      administration of 1% DSS. The increased severity of colitis in Nrf2(-/-) mice was
      found to be associated with decreased expression of antioxidant/phase II
      detoxifying enzymes including heme-oxygenase-1, NAD(P)H-quinone reductase-1, UDP
      glucurosyltransferase 1A1, and glutathione S-transferase Mu-1. In addition,
      proinflammatory mediators/cytokines such as COX-2, inducible nitric oxide,
      interleukin 1beta, interleukin 6, and tumor necrosis factor alpha were
      significantly increased in the colonic tissues of Nrf2(-/-) mice compared with
      their wild-type (Nrf2+/+) counterparts. In summary, we show for the first time
      that mice lacking Nrf2 are more susceptible to DSS-induced colitis. Our data
      suggests that Nrf2 could play an important role in protecting intestinal
      integrity, through regulation of proinflammatory cytokines and induction of phase
      II detoxifying enzymes.

PMID- 17178850
TI  - Physical association with WWOX suppresses c-Jun transcriptional activity.
AB  - WWOX is a tumor suppressor that functions as a modular protein partner of
      transcription factors. WWOX contains two WW domains that mediate protein-protein
      interactions. In this report, we show that WWOX, via its first WW domain,
      specifically associates with the proline-rich motif of c-Jun proto-oncogene. Our
      data show that phosphorylation of c-Jun caused by overexpression of mitogen
      activated protein kinase kinase kinase 1 (Mekk1), an upstream activator of c-Jun,
      enhances the interaction of c-Jun with WWOX. Furthermore, exposure of HaCaT
      keratinocytes to UVC radiation resulted in the association of endogenous WWOX and
      c-Jun. The WWOX-c-Jun complexes mainly occur in the cytoplasm. Expression of WWOX
      attenuates the ability of MEKK1 to increase the activity of a c-Jun-driven
      activating protein-1 (AP-1)-luciferase reporter plasmid. In contrast, a point
      mutation in the first WW domain of WWOX has no effect on transactivation of AP-1
      when coexpressed with c-Jun protein. Our findings reveal a novel functional cross
      talk between c-Jun transcription factor and WWOX tumor suppressor protein.

PMID- 17178852
TI  - KAP1, a novel substrate for PIKK family members, colocalizes with numerous damage
      response factors at DNA lesions.
AB  - The DNA damage response requires a coordinated nucleo-cytoplasmic cascade of
      events, which ultimately converge on damaged DNA packaged in chromatin. Few
      connections between the proteins that remodel chromatin and the proteins that
      mediate this damage response have been shown. We have investigated the DNA damage
      induced phosphorylation of the KRAB-ZFP-associated protein 1 (KAP1), the
      dedicated corepressor for Kruppel-associated box (KRAB) zinc finger protein (ZFP)
      proteins. We show that KAP1 is rapidly phosphorylated following DNA damage by
      members of the phosphatidylinositol-3 kinase-like family of kinases. This
      phosphorylation occurs at a single amino acid residue that is conserved from mice
      to humans and is located adjacent to the bromodomain, suggesting that it may
      regulate chromatin recognition by that module. Phosphorylated KAP1 rapidly
      localizes to sites of DNA strand breaks in the nucleus in response to ionizing
      radiation. This discovery provides a novel link between chromatin-mediated
      transcriptional repression and the recognition/repair of DNA, which must be
      accomplished by the cellular DNA damage response.

PMID- 17178851
TI  - Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR
      181.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is the most common human leukemia in
      the world. Deregulation of the TCL1 oncogene is a causal event in the
      pathogenesis of the aggressive form of this disease as was verified by using
      animal models. To study the mechanism of Tcl1 regulation in CLL, we carried out
      microRNA expression profiling of three types of CLL: indolent CLL, aggressive
      CLL, and aggressive CLL showing 11q deletion. We identified distinct microRNA
      signatures corresponding to each group of CLL. We further determined that Tcl1
      expression is regulated by miR-29 and miR-181, two microRNAs differentially
      expressed in CLL. Expression levels of miR-29 and miR-181 generally inversely
      correlated with Tcl1 expression in the CLL samples we examined. Our results
      suggest that Tcl1 expression in CLL is, at least in part, regulated by miR-29 and
      miR-181 and that these microRNAs may be candidates for therapeutic agents in CLLs
      overexpressing Tcl1.

PMID- 17178853
TI  - Asbestos redirects nitric oxide signaling through rapid catalytic conversion to
      nitrite.
AB  - Asbestos exposure is strongly associated with the development of malignant
      mesothelioma, yet the mechanistic basis of this observation has not been
      resolved. Carcinogenic transformation or tumor progression mediated by asbestos
      may be related to the generation of free radical species and perturbation of cell
      signaling and transcription factors. We report here that exposure of human
      mesothelioma or lung carcinoma cells to nitric oxide (NO) in the presence of
      crocidolite asbestos resulted in a marked decrease in intracellular nitrosation
      and diminished NO-induced posttranslational modifications of tumor-associated
      proteins (hypoxia-inducible factor-1alpha and p53). Crocidolite rapidly scavenged
      NO with concomitant conversion to nitrite (NO(2)(-)). Crocidolite also catalyzed
      the nitration of cellular proteins in the presence of NO(2)(-) and hydrogen
      peroxide. Nitrated protein adducts are a prominent feature of asbestos-induced
      lung injury. These data highlight the ability of asbestos to induce phenotypic
      cellular changes through two processes: (a) by directly reducing bioactive NO
      levels and preventing its subsequent interaction with target molecules and (b) by
      increasing oxidative damage and protein modifications through NO(2) production
      and 3-nitrotyrosine formation.

PMID- 17178854
TI  - Comparison of kinome profiles of Barrett's esophagus with normal squamous
      esophagus and normal gastric cardia.
AB  - The precursor metaplastic mucosal lesion that predisposes for esophageal
      adenocarcinoma is Barrett's esophagus. Because the signal transduction events
      that occur in Barrett's esophagus are poorly understood, this study aimed at
      generating a comprehensive description of cellular kinase activity in Barrett's
      esophagus, normal squamous esophagus, and gastric cardia to gain more insight
      into the pathogenesis of Barrett's esophagus. Peptide arrays, exhibiting 1,176
      specific consensus sequences for protein kinases, were used to produce a global
      analysis of cellular kinase activity in biopsies of Barrett's esophagus, and
      results were compared with the neighboring cardia and squamous epithelia. Several
      differences in kinase activity using immunoblot analysis and enzyme activity
      assays were validated in biopsies of 27 Barrett's esophagus patients. Three
      unique kinome profiles are described and compared. We identified cascades of
      activated kinases showing that mitogen-activated protein kinase and epidermal
      growth factor receptor activity are both significantly altered in Barrett's
      esophagus compared with squamous and gastric cardia epithelia. Another novel
      finding is that the glycolysis pathway is significantly up-regulated in Barrett's
      esophagus, which is illustrated by an up-regulated pyruvate kinase activity.
      Here, the unique kinome profile of Barrett's esophagus is made available as a
      comprehensive database. Several signaling pathways are revealed as specifically
      expressed in Barrett's esophagus when compared with the adjacent normal
      epithelia. These unique findings provide novel insight in the pathogenesis of
      Barrett's esophagus that will ultimately help to resolve the increasing problem
      of Barrett's esophagus and prevention of esophageal adenocarcinoma.

PMID- 17178855
TI  - HMGA1 is a determinant of cellular invasiveness and in vivo metastatic potential
      in pancreatic adenocarcinoma.
AB  - HMGA1 proteins are architectural transcription factors that are overexpressed in
      a range of human malignancies, including pancreatic adenocarcinoma. We
      hypothesized that HMGA1 expression is a determinant of cellular invasiveness and
      metastasis in pancreatic cancer. Stable silencing of HMGA1 in MiaPaCa2 and PANC1
      pancreatic adenocarcinoma cells was achieved by transfection of short hairpin RNA
      generating vectors. Additionally, stable overexpression of HMGA1 in MiaPaCa2
      cells (characterized by low levels of inherent HMGA1 expression) was achieved.
      HMGA1 silencing resulted in significant reductions in cellular invasiveness
      through Matrigel; in cellular matrix metalloproteinase-9 (MMP-9) activity, mRNA
      levels, and gene promoter activity; and in Akt phosphorylation at Ser(473).
      Conversely, forced HMGA1 overexpression resulted in significant increases in
      cellular invasiveness; in cellular MMP-9 activity, mRNA levels, and promoter
      activity; and in Akt phosphorylation at Ser(473). HMGA1 overexpression-induced
      increases in invasiveness were MMP-9 dependent. The role of phosphatidylinositol
      3 kinase (PI3K)/Akt in mediating HMGA1-dependent invasiveness was elucidated by a
      specific PI3K inhibitor (LY294002) and constitutively active and dominant
      negative Akt adenoviral constructs. Akt-dependent modulation of MMP-9 activity
      contributed significantly to HMGA1 overexpression-induced increases in invasive
      capacity. Furthermore, HMGA1 silencing resulted in reductions in metastatic
      potential and tumor growth in vivo and in tumoral MMP-9 activity. Our findings
      suggest that HMGA1 may be a novel molecular determinant of invasiveness and
      metastasis, as well as a potential therapeutic target, in pancreatic
      adenocarcinoma.

PMID- 17178856
TI  - Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma
      cell invasiveness and metastasis.
AB  - A reduced expression level of the cyclin-dependent kinase inhibitor p27(Kip1) is
      associated with increased tumor malignancy and poor prognosis in individuals with
      various types of cancer. To investigate the basis for this relation, we applied
      microarray analysis to screen for genes differentially expressed between p27(+/-)
      and parental (p27(+/+)) HCT116 human colon carcinoma cells. Expression of the
      gene for G protein-coupled receptor 48 (GPR48) was increased in the p27(+/-)
      cells. Forced expression of GPR48 increased both in vitro invasive activity and
      lung metastasis potency of HCT116 cells. In contrast, depletion of endogenous
      GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung
      carcinoma cells not only in vitro but also in vivo. Moreover, GPR48 expression
      was significantly associated with lymph node metastasis and inversely correlated
      with p27 expression in human colon carcinomas. GPR48 may thus play an important
      role in invasiveness and metastasis of carcinoma and might therefore represent a
      potential prognostic marker or therapeutic target.

PMID- 17178857
TI  - Multiple interacting oncogenes on the 8p11-p12 amplicon in human breast cancer.
AB  - The 8p11-p12 genomic region is amplified in 15% of breast cancers and harbors
      several candidate oncogenes. However, functional evidence for a transforming role
      for these genes is lacking. We identified 21 genes from this region as potential
      oncogenes based on statistical association between copy number and expression. We
      further showed that three of these genes (LSM1, BAG4, and C8orf4) induce
      transformed phenotypes when overexpressed in MCF-10A cells, and overexpression of
      these genes in combination influences the growth factor independence phenotype
      and the ability of the cells to grow under anchorage-independent conditions.
      Thus, LSM1, BAG4, and C8orf4 are breast cancer oncogenes that can work in
      combination to influence the transformed phenotype in human mammary epithelial
      cells.

PMID- 17178858
TI  - Matrix metalloproteinase polymorphisms and bladder cancer risk.
AB  - Matrix metalloproteinases (MMP) contribute to tumor microenvironment and are
      associated with bladder cancer. A study examining the association between MMP
      polymorphisms and bladder cancer risk has never been published. We analyzed the
      association of 11 single nucleotide polymorphisms (SNPs) and one microsatellite
      polymorphism in MMP genes MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-12 with
      bladder cancer risk in 560 Caucasian patients and 560 controls matched on age,
      gender, and ethnicity. Individual, combination, haplotype, and diplotype analyses
      were done. No associations between individual MMP polymorphisms and overall
      bladder cancer risk were seen. The MMP-9 microsatellite > or =24 CA repeat allele
      and the MMP-12-82 GG polymorphisms were associated with invasive bladder cancer
      risk [odds ratio (OR), 2.60; 95% confidence interval (95% CI), 1.07-6.26; and OR,
      4.59; 95% CI, 1.21-17.32, respectively]. Smoke-stratified analyses revealed
      several associations between MMP polymorphisms, alone and in combination, with
      bladder cancer risk, particularly in light smokers. Linkage disequilibrium was
      seen in all of the MMP-1, MMP-3, MMP-8, and MMP-12 SNPs and in four of five MMP-9
      polymorphisms tested. Several MMP-9 haplotype and diplotypes were associated with
      overall and invasive bladder cancer risk. Our study suggests that genetic
      variations in the MMP family are associated with bladder cancer risk. Heavy
      carcinogen exposure may overwhelm some of the genetic effects of MMP
      polymorphisms. Our study confirms the importance of taking a multigenic pathway
      based approach to risk assessment.

PMID- 17178859
TI  - Identification of cyclin D1- and estrogen-regulated genes contributing to breast
      carcinogenesis and progression.
AB  - Tumors can become lethal when they progress from preinvasive lesions to invasive
      carcinomas. Here, we identify candidate tumor progression genes using gene array
      analysis of preinvasive and invasive tumors from mice, which were then evaluated
      in human cancers. Immediate early response protein IEX-1, small stress protein 1
      (HSPB8), and tumor necrosis factor-associated factor-interacting protein mRNAs
      displayed higher expression levels in invasive lesions than in preinvasive
      lesions using samples obtained by laser capture microdissection (LCM) from
      transgenic erbB2, ras, and cyclin D1 mice. LCM-isolated tissues from patient
      matched normal, ductal carcinoma in situ, and invasive ductal carcinoma revealed
      similar increased expression in invasive human cancers compared with preinvasive
      and normal samples. These genes induced anchorage independence, increased cell
      proliferation, and protected against apoptosis, singly or in collaboration with
      erbB2. Surprisingly, they were all up-regulated by 17beta-estradiol and cyclin
      D1, and cyclin D1 overexpression increased p300/CBP binding to their promoters,
      supporting the model that cyclin D1-estrogen receptor (ER) coactivator
      interactions may be important to its role in ER-positive breast cancer.
      Additionally, an irreversible dual kinase inhibitor of ErbB signaling inhibited
      expression of the same genes. The up-regulation of genes contributing to
      increased invasiveness of ER-positive cancers offers a novel explanation for the
      contribution of cyclin D1 to a worse prognosis in ER-positive cancers. As targets
      of estrogen, cyclin D1, and erbB2 signaling, these candidates offer insights into
      the nature of the second events involved in breast cancer progression, regulatory
      events contributing to invasion, and potential targets of combined inhibition of
      hormone and growth factor signaling pathways.

PMID- 17178860
TI  - DNA methylation pathway alterations in an autochthonous murine model of prostate
      cancer.
AB  - We examined the DNA methylation pathway in an autochthonous murine prostate
      cancer model, transgenic adenocarcinoma of mouse prostate (TRAMP). We observed
      that, compared with strain-matched normal prostates, primary and metastatic TRAMP
      tumors display increased cytosine DNA methyltransferase (Dnmt) activity, Dnmt1
      and Dnmt3b protein expression, and Dnmt1, Dnmt3a, and Dnmt3b mRNA expression.
      Increased expression of Dnmt genes correlates with increased expression of cyclin
      A and E2F target genes, implicating increased cell proliferation and Rb
      inactivation in Dnmt overexpression. We analyzed DNA methylation in TRAMP and
      found that global levels of 5-methyl-2'-deoxycytidine are unaltered, whereas
      specific tumors display centromeric repeat hypomethylation. To interrogate locus
      specific methylation, we did restriction landmark genomic scanning (RLGS) on
      normal prostates and primary tumors. In primary tumors, 2.3% of approximately
      1,200 analyzed loci display aberrant DNA hypermethylation, whereas a considerably
      smaller number of events show hypomethylation. The pattern of RLGS changes was
      nonrandom, indicating a coordinated methylation defect. Two specific genes
      identified by RLGS were studied in detail. Surprisingly, methylation of a
      downstream exon of p16(INK4a) (p16) was the highest frequency hypermethylation
      event identified in TRAMP, where it is associated with increased p16 mRNA and
      protein expression. In contrast, hypermethylation of the 5' CpG island region of
      the homeobox gene Irx3 in TRAMP is associated with reduced gene expression. In
      summary, our data reveal a systemic DNA methylation pathway defect in TRAMP
      reminiscent of human prostate cancer, supporting the use of this model to
      investigate the functional role of DNA methylation pathway alterations in
      prostate cancer development.

PMID- 17178861
TI  - Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal
      kinase signaling.
AB  - EBV latent membrane protein 1 (LMP1) activates cellular DNA methyltransferases,
      resulting in hypermethylation and silencing of E-cadherin. However, the
      underlying mechanism remains to be elucidated. In this study, we show that LMP1
      directly induces the dnmt1 promoter activity through its COOH-terminal activation
      region-2 YYD domain. Using (i) LMP1 mutants, (ii) dominant negative mutants c-jun
      NH(2)-terminal kinase (JNK)-DN, p38-DN, and constitutive active mutant IkappaB,
      as well as (iii) dsRNAs targeting c-Jun, JNK, and tumor necrosis factor receptor
      associated death domain protein, and (iv) signal transduction inhibitors, we show
      that LMP1-mediated DNA methyltransferase-1 (DNMT1) activation involves JNK but
      not nuclear factor kappaB and p38/mitogen-activated protein kinase signaling. In
      addition, LMP1 is unable to activate dnmt1-P1 promoter with activator protein-1
      (AP-1) site mutation. Chromatin immunoprecipitation assay results also confirm
      that LMP1 activates P1 promoter via the JNK-AP-1 pathway. Furthermore, chromatin
      immunoprecipitation assay data in LMP1-inducible cells disclose that LMP1 induces
      formation of a transcriptional repression complex, composed of DNMT1 and histone
      deacetylase, which locates on E-cadherin gene promoter. Treatment with JNK
      inhibitor, SP600125, prevents the formation of this repression complex.
      Statistical analyses of the immunohistochemical staining of 32 nasopharyngeal
      carcinoma (NPC) biopsies show LMP1 expression (18 of 32, 56.25%), DNMT1
      expression (31 of 32, 97%), and phospho-c-Jun (27 of 32, 84.38%), suggesting that
      overexpression of these proteins is observed in NPC tumor. Overall, these results
      support a mechanistic link between JNK-AP-1 signaling and DNA methylation induced
      by the EBV oncogene product LMP1.

PMID- 17178862
TI  - Nuclear localization of PTEN is regulated by Ca(2+) through a tyrosil
      phosphorylation-independent conformational modification in major vault protein.
AB  - We have recently shown in MCF-7 cells that nuclear phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) down-regulates phosphorylation of
      p44/42 and cyclin D1 and induces G(1) cell cycle arrest, whereas cytoplasmic PTEN
      down-regulates phosphorylation of Akt, up-regulates p27, and induces apoptosis.
      In this manner, nucleocytoplasmic partitioning of PTEN seems to differentially
      regulate the cell cycle and apoptosis. We have also reported that PTEN has
      nuclear localization signal-like sequences required for major vault protein (MVP)
      mediated nuclear translocation. To date, several other proteins are reported to
      interact with MVP, including extracellular signal-regulated kinases and steroid
      receptors, suggesting that MVP is likely to be involved in signal transduction
      through nucleocytoplasmic transport. However, the exact mechanism of MVP-mediated
      nucleocytoplasmic shuttling remains elusive. PTEN reportedly interacts in vitro
      with the EF hand-like motif of MVP in a Ca(2+)-dependent manner. The current
      study shows that small interfering RNA-mediated MVP silencing decreases the
      nuclear localization of PTEN and increases phosphorylation of nuclear p44/42. We
      show in situ that PTEN-MVP interaction is Ca(2+) dependent and is abolished by
      Mg(2+). Nuclear localization of PTEN is decreased by increasing Ca(2+) levels in
      culture medium in a dose-dependent manner. Ca(2+) ionophore A23187 increases
      nuclear localization of PTEN and decreases phosphorylation of nuclear p44/42.
      Finally, we show that Ca(2+)-dependent PTEN-MVP interaction is not related to
      MVP's tyrosil phosphorylation but rather due to its conformational modification.
      Our observations suggest that Ca(2+) regulates PTEN's nuclear entry through a
      tyrosil phosphorylation-independent conformational change in MVP. Collectively,
      our data present evidence of a novel crosstalk between the Ca(2+) signaling
      mediated regulation of the cell cycle and MVP-mediated nuclear PTEN localization
      and function.

PMID- 17178863
TI  - Reduced repair of the oxidative 8-oxoguanine DNA damage and risk of head and neck
      cancer.
AB  - An increasing number of studies indicate that reduced DNA-repair capacity is
      associated with increased cancer risk. Using a functional assay for the removal
      of the oxidative DNA lesion 8-oxoguanine by the DNA-repair enzyme 8-oxoguanine
      DNA glycosylase 1 (OGG1), we have previously shown that reduced OGG activity is a
      risk factor in lung cancer. Here, we report that OGG activity in peripheral blood
      mononuclear cells from 37 cases with squamous cell carcinoma of the head and neck
      (SCCHN) was significantly lower than in 93 control subjects, frequency matched
      for age and gender. Retesting of OGG activity 3 to 4 years after diagnosis and
      successful treatment of 18 individuals who recovered from the disease showed that
      OGG activity values were similar to those determined at diagnosis, suggesting
      that reduced OGG activity in case patients was not caused by the disease.
      Logistic regression analysis indicated that the adjusted odds ratio (OR)
      associated with a unit decrease in OGG activity was statistically significantly
      increased [OR, 2.3; 95% confidence interval (95% CI), 1.5-3.4]. Individuals in
      the lowest tertile of OGG activity exhibited an increased risk of SCCHN with an
      OR of 7.0 (95% CI, 2.0-24.5). The combination of smoking and low OGG was
      associated with a highly increased estimated relative risk for SCCHN. These
      results suggest that low OGG is associated with the risk of SCCHN, and if
      confirmed by additional epidemiologic studies, screening of smokers for low OGG
      activity might be used as a strategy for the prevention of lung cancer and SCCHN.

PMID- 17178864
TI  - Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of
      esophageal squamous cell carcinoma by promoting cell migration and anoikis
      resistance.
AB  - Gain of chromosome 11q13 is a common event in esophageal squamous cell carcinoma
      (ESCC). The cortactin gene (CTTN, also EMS1), located at 11q13, plays a pivotal
      role in coupling membrane dynamics to cortical actin assembly. This gene has been
      implicated in the motility of several types of cells. In the present study, we
      found that the amplification and overexpression of the CTTN gene was associated
      with lymph node metastasis in ESCC. Functional analysis by small interfering RNA
      mediated silencing of CTTN revealed that in addition to the effect on cell
      migration, CTTN influenced cell invasiveness by anoikis resistance. In vivo assay
      showed that inhibition of CTTN expression also decreased tumor growth and lung
      metastasis of ESCC cells. At the molecular level, we showed for the first time
      that the protective role of CTTN in anoikis resistance was correlated with the
      activation of the phosphatidylinositol 3-kinase/Akt pathway. Overall, the data
      suggest that CTTN is an oncogene in the 11q13 amplicon and exerts functions on
      tumor metastasis in ESCC.

PMID- 17178865
TI  - RhoA mediates cyclooxygenase-2 signaling to disrupt the formation of adherens
      junctions and increase cell motility.
AB  - Cyclooxygenase-2 (COX-2) represents an important target for treatment and
      prevention of colorectal cancer. Although COX-2 signaling is implicated in
      promoting tumor cell growth and invasion, the molecular mechanisms that mediate
      these processes are largely unknown. In this study, we show that the RhoA pathway
      mediates COX-2 signaling to disrupt the formation of adherens junctions and
      increase cell motility. Disruption of adherens junctions promotes tumor cell
      invasion and metastasis and is often associated with tumor progression. We
      detected high levels of RhoA activity in HCA-7 colon carcinoma cells that
      constitutively express COX-2. Inhibition of COX-2 significantly reduced the
      levels of RhoA activity in HCA-7 cells, suggesting that constitutive expression
      of COX-2 stimulates RhoA activity. Interestingly, inhibition of COX-2 or
      silencing of COX-2 expression with small interfering RNA (siRNA) stimulated the
      formation of adherens junctions, concomitant with increased protein levels of E
      cadherin and alpha-catenin. Furthermore, inhibition of RhoA or silencing of RhoA
      expression with siRNA increased the levels of E-cadherin and alpha-catenin.
      Inhibition of Rho kinases (ROCK), the RhoA effector proteins, also increased
      levels of E-cadherin and alpha-catenin and stimulated formation of adherens
      junctions. The motility of HCA-7 cells was significantly decreased when COX-2 or
      RhoA was inhibited. Therefore, our data reveal a novel molecular mechanism that
      links COX-2 signaling to disrupt the formation of adherens junctions; COX-2
      stimulates the RhoA/ROCK pathway, which reduces levels of E-cadherin and alpha
      catenin leading to disruption of adherens junction formation and increased
      motility. Understanding of COX-2 downstream signaling pathways that promote tumor
      progression is crucial for the development of novel therapeutic strategies.

PMID- 17178866
TI  - A Ras inhibitor tilts the balance between Rac and Rho and blocks
      phosphatidylinositol 3-kinase-dependent glioblastoma cell migration.
AB  - Glioblastoma multiforme are highly aggressive tumors for which no adequate
      treatment has yet been developed. Glioblastoma multiforme show large amounts of
      active Ras, considered an appropriate target for directed therapy. Here, we show
      that the Ras inhibitor S-trans, trans-farnesyl thiosalicylic acid (FTS) can avert
      the transformation of human glioblastoma multiforme cells by inhibiting both
      their migration and their anchorage-independent proliferation. FTS, by down
      regulating Ras activity in glioblastoma multiforme cells, inhibited
      phosphatidylinositol 3-kinase signaling, resulting in decreased activity of Rac
      1. At the same time, activation of RhoA was increased. These two small GTPases
      are known to control the arrangement of the actin cytoskeleton. By tilting the
      balance between Rac-1 and RhoA activities, FTS caused the glioblastoma multiforme
      cells to undergo profound changes in morphology, including rearrangement of actin
      into stress fibers and assembly of focal adhesions, both of which are governed by
      RhoA signaling. These morphologic changes allowed strong attachment of the cells
      to the matrix, rendering them immobile. The results show that FTS should be
      considered as a candidate drug for glioblastoma multiforme therapy because it
      targets not only cell proliferation but also cell migration and invasion, which
      together constitute the most problematic aspect of these malignancies.

PMID- 17178867
TI  - A specific role for AKT3 in the genesis of ovarian cancer through modulation of
      G(2)-M phase transition.
AB  - Ovarian cancer is the major cause of death from gynecological malignancy, and
      there is an urgent need for new therapeutic targets. The phosphatidylinositol 3
      kinase (PI3K)/AKT pathway has been strongly implicated in the genesis of ovarian
      cancer. However, to identify and evaluate potential targets for therapeutic
      intervention, it is critical to understand the mechanism by which the PI3K/AKT
      pathway facilitates ovarian carcinogenesis. Here, we show that AKT3 is highly
      expressed in 19 of 92 primary ovarian tumors. Strikingly, purified AKT3 exhibited
      up to 10-fold higher specific activity than AKT1, potentially amplifying the
      effects of AKT3 overexpression. Consistent with this finding, AKT3 levels in a
      range of ovarian cancer cell lines correlated with total AKT activity and
      proliferation rates, implicating AKT3 as a key mediator of ovarian oncogenesis.
      Specific silencing of AKT3 using short hairpin RNA markedly inhibited
      proliferation of the two cell lines with highest AKT3 expression and total AKT
      activity, OVCA429 and DOV13, by slowing G(2)-M phase transition. These findings
      are consistent with AKT3 playing a key role in the genesis of at least one subset
      of ovarian cancers.

PMID- 17178868
TI  - Ectopic doublecortin gene expression suppresses the malignant phenotype in
      glioblastoma cells.
AB  - Doublecortin (DCX) is one of the three genes found from Affymetrix gene chip
      analysis related to glioma patient survival. Two other genes (e.g., osteonectin
      and semaphorin 3B) are well characterized as antioncogenic and tumor suppressor
      genes. However, there is no report about the involvement of DCX in cancer. Here,
      we show that gene transfer technology into DCX-deficient glioblastoma cell lines,
      such as A172, U87, U251N, RG2, and 9L, with DCX cDNA significantly suppressed
      growth of these glioma cells. U87 cells with ectopic expression of DCX exhibit a
      marked suppression of the transformed phenotype as growth arrested in the G(2)
      phase of the cell cycle progression, small colony formation in soft agar, and no
      tumor formation in nude rats. This transformed phenotype can be restored by
      knocking down DCX expression with DCX small interfering RNA. DCX was highly
      phosphorylated in glioma cells. Phosphorylation in the glioma cells was greater
      than in noncancer cells such as mouse NIH 3T3 and human embryonic kidney 293T
      cells. Coimmunoprecipitation of the phosphorylated DCX and spinophilin/neurabin
      II from DCX-synthesizing glioma cells indicated their interaction. This
      interaction would lead to a block of anchorage-independent growth as neurabin II
      is a synergistic inhibitor of anchorage-independent growth with p14ARF (ARF).
      Interaction between phosphorylated DCX and neurabin II may induce the association
      of the protein phosphatase 1 catalytic subunit (PP1) with neurabin II and
      inactivate PP1 and block mitosis during G(2) and M phases of the cell cycle
      progression. Thus, DCX seems to be a tumor suppressor of glioma.

PMID- 17178869
TI  - Preconditioning of the tumor vasculature and tumor cells by intermittent hypoxia:
      implications for anticancer therapies.
AB  - Hypoxia is a common feature in tumors associated with an increased resistance of
      tumor cells to therapies. In addition to O(2) diffusion-limited hypoxia, another
      form of tumor hypoxia characterized by fluctuating changes in pO(2) within the
      disorganized tumor vascular network is described. Here, we postulated that this
      form of intermittent hypoxia promotes endothelial cell survival, thereby
      extending the concept of hypoxia-driven resistance to the tumor vasculature. We
      found that endothelial cell exposure to cycles of hypoxia reoxygenation not only
      rendered them resistant to proapoptotic stresses, including serum deprivation and
      radiotherapy, but also increased their capacity to migrate and organize in tubes.
      By contrast, prolonged hypoxia failed to exert protective effects and even seemed
      deleterious when combined with radiotherapy. The use of hypoxia-inducible factor
      1alpha (HIF-1alpha)-targeting small interfering RNA led us to document that the
      accumulation of HIF-1alpha during intermittent hypoxia accounted for the higher
      resistance of endothelial cells. We also used an in vivo approach to enforce
      intermittent hypoxia in tumor-bearing mice and found that it was associated with
      less radiation-induced apoptosis within both the vascular and the tumor cell
      compartments (versus normoxia or prolonged hypoxia). Radioresistance was further
      ascertained by an increased rate of tumor regrowth in irradiated mice preexposed
      to intermittent hypoxia and confirmed in vitro using distinctly radiosensitive
      tumor cell lines. In conclusion, we have documented that intermittent hypoxia may
      condition endothelial cells and tumor cells in such a way that they are more
      resistant to apoptosis and more prone to participate in tumor progression. Our
      observations also underscore the potential of drugs targeting HIF-1alpha to
      resensitize the tumor vasculature to anticancer treatments.

PMID- 17178870
TI  - Collagen I promotes metastasis in pancreatic cancer by activating c-Jun NH(2)
      terminal kinase 1 and up-regulating N-cadherin expression.
AB  - We have previously shown that N-cadherin expression is associated with tumor
      invasion, and that some cancer cells respond to specific extracellular matrix
      molecules by up-regulating N-cadherin. Pancreatic cancer is characterized by
      excessive deposition of type I collagen. Here, we show that human pancreatic
      cancer cells respond to collagen I, but not other matrices, by increasing
      motility and up-regulating mesenchymal markers, including N-cadherin. Both
      collagen I-mediated motility and metastasis in a mouse model for pancreatic
      cancer were inhibited by N-cadherin knockdown. Furthermore, inhibiting c-Jun
      NH(2)-terminal kinase (JNK) with chemical inhibitors or short hairpin RNA
      abrogated all collagen I-induced changes. We show that JNK1 is activated in
      response to collagen I, which increases tumorigenesis by up-regulating N-cadherin
      expression and by increasing motility.

PMID- 17178871
TI  - Calmodulin-androgen receptor (AR) interaction: calcium-dependent, calpain
      mediated breakdown of AR in LNCaP prostate cancer cells.
AB  - Chemotherapy of prostate cancer targets androgen receptor (AR) by androgen
      ablation or antiandrogens, but unfortunately, it is not curative. Our attack on
      prostate cancer envisions the proteolytic elimination of AR, which requires a
      fuller understanding of AR turnover. We showed previously that calmodulin (CaM)
      binds to AR with important consequences for AR stability and function. To examine
      the involvement of Ca(2+)/CaM in the proteolytic breakdown of AR, we analyzed
      LNCaP cell extracts that bind to a CaM affinity column for the presence of low
      molecular weight forms of AR (intact AR size, approximately 114 kDa). Using an
      antibody directed against the NH(2)-terminal domain (ATD) of AR on Western blots,
      we identified approximately 76-kDa, approximately 50-kDa, and 34/31-kDa
      polypeptides in eluates of CaM affinity columns, suggesting the presence of CaM
      binding sites within the 31/34-kDa ATD of AR. Under cell-free conditions in the
      presence of phenylmethylsulfonyl fluoride, AR underwent Ca(2+)-dependent
      degradation. AR degradation was inhibited by N-acetyl-leu-leu-norleu, an
      inhibitor of thiol proteases, suggesting the involvement of calpain. In intact
      cells, AR breakdown was accelerated by raising intracellular Ca(2+) using
      calcimycin, and increased AR breakdown was reversed with the cell-permeable
      Ca(2+) chelator bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra
      (acetoxymethyl)-ester. In CaM affinity chromatography studies, the Ca(2+)
      dependent protease calpain was bound to and eluted from the CaM-agarose column
      along with AR. Caspase-3, which plays a role in AR turnover under stress
      conditions, did not bind to the CaM column and was present in the proenzyme form.
      Similarly, AR immunoprecipitates prepared from whole-cell extracts of
      exponentially growing LNCaP cells contained both calpain and calpastatin. Nuclear
      levels of calpain and calpastatin (its endogenous inhibitor) changed in a
      reciprocal fashion as synchronized LNCaP cells progressed from G(1) to S phase.
      These reciprocal changes correlated with changes in AR level, which increased in
      late G(1) phase and decreased as S phase progressed. Taken together, these
      observations suggest potential involvement of AR-bound CaM in calcium-controlled,
      calpain-mediated breakdown of AR in prostate cancer cells.

PMID- 17178872
TI  - Human kallikrein 8 protease confers a favorable clinical outcome in non-small
      cell lung cancer by suppressing tumor cell invasiveness.
AB  - The human kallikrein 8 (KLK8) gene, a member of the human tissue kallikrein gene
      family, encodes a serine protease. The KLK8 protein (hK8) is known to be a
      favorable prognostic marker in ovarian cancer, but the biological basis of this
      is not understood. We found that overexpressing the KLK8 gene in highly invasive
      lung cancer cell lines suppresses their invasiveness. This role in invasiveness
      was further confirmed by the fact that inhibition of endogenous KLK8 expression
      with a specific short hairpin RNA reduced cancer cell invasiveness. In situ
      degradation and cell adhesion assays showed that proteins produced from KLK8
      splice variants modify the extracellular microenvironment by cleaving
      fibronectin. DNA microarray experiments and staining of cells for actin filaments
      revealed that the degradation of fibronectin by hK8 suppresses integrin signaling
      and retards cancer cell motility by inhibiting actin polymerization. In addition,
      studies in a mouse model coupled with the detection of circulating tumor cells by
      quantitative PCR for the human Alu sequence showed that KLK8 suppresses tumor
      growth and invasion in vivo. Finally, studies of clinical specimens from patients
      with non-small cell lung cancer showed that the time to postoperative recurrence
      was longer for early-stage patients (stages I and II) with high KLK8 expression
      (mean, 49.9 months) than for patients with low KLK8 expression (mean, 22.9
      months). Collectively, these findings show that KLK8 expression confers a
      favorable clinical outcome in non-small cell lung cancer by suppressing tumor
      cell invasiveness.

PMID- 17178873
TI  - Tenascin-C stimulates glioma cell invasion through matrix metalloproteinase-12.
AB  - The capacity of glioma cells to invade extensively within the central nervous
      system is a major cause of the high morbidity rate of primary malignant brain
      tumors. Glioma cell invasion involves the attachment of tumor cells to
      extracellular matrix (ECM), degradation of ECM components, and subsequent
      penetration into adjacent brain structures. These processes are accomplished in
      part by matrix metalloproteinases (MMP) within a three-dimensional milieu of the
      brain parenchyma. As the majority of studies have used a two-dimensional
      monolayer culture system, we have used a three-dimensional matrix of collagen
      type I gel to address glioma-secreted proteases, ECM, and invasiveness of glioma
      cells. We show that in a three-dimensional collagen type I matrix, the presence
      of tenascin-C, commonly elevated in high-grade gliomas, increased the
      invasiveness of glioma cells. The tenascin-C-mediated invasiveness was blocked by
      metalloproteinase inhibitors, but this did not involve the gelatinases (MMP-2 and
      MMP-9) commonly implicated in two-dimensional glioma growth. A thorough analysis
      of 21 MMPs and six members of a disintegrin and metalloproteinase domain showed
      that MMP-12 was increased in gliomas by tenascin-C in three-dimensional matrix.
      Furthermore, examinations of resected specimens revealed high MMP-12 levels in
      the high-grade glioblastoma multiforme tumors. Finally, a function-blocking
      antibody as well as small interfering RNA to MMP-12 attenuated the tenascin-C
      stimulated glioma invasion. These results identify a new factor, MMP-12, in
      regulating glioma invasiveness through interaction with tenascin-C.

PMID- 17178874
TI  - Enforced expression of NUP98-HOXA9 in human CD34(+) cells enhances stem cell
      proliferation.
AB  - The t(7;11)(p15;p15) translocation, observed in acute myelogenous leukemia and
      myelodysplastic syndrome, generates a chimeric gene where the 5' portion of the
      sequence encoding the human nucleoporin NUP98 protein is fused to the 3' region
      of HOXA9. Here, we show that retroviral-mediated enforced expression of the NUP98
      HOXA9 fusion protein in cord blood-derived CD34(+) cells confers a proliferative
      advantage in both cytokine-stimulated suspension cultures and stromal coculture.
      This advantage is reflected in the selective expansion of hematopoietic stem
      cells as measured in vitro by cobblestone area-forming cell assays and in vivo by
      competitive repopulation of nonobese diabetic/severe combined immunodeficient
      mice. NUP98-HOXA9 expression inhibited erythroid progenitor differentiation and
      delayed neutrophil maturation in transduced progenitors but strongly enhanced
      their serial replating efficiency. Analysis of the transcriptosome of transduced
      cells revealed up-regulation of several homeobox genes of the A and B cluster as
      well as of Meis1 and Pim-1 and down-modulation of globin genes and of
      CAAT/enhancer binding protein alpha. The latter gene, when coexpressed with NUP98
      HOXA9, reversed the enhanced proliferation of transduced CD34(+) cells. Unlike
      HOXA9, the NUP98-HOXA9 fusion was protected from ubiquitination mediated by
      Cullin-4A and subsequent proteasome-dependent degradation. The resulting protein
      stabilization may contribute to the leukemogenic activity of the fusion protein.

PMID- 17178875
TI  - Androgens regulate protein kinase Cdelta transcription and modulate its apoptotic
      function in prostate cancer cells.
AB  - Activation of protein kinase Cdelta (PKCdelta), a member of the novel PKC family,
      leads to apoptosis in several cell types. Although the molecular bases of
      PKCdelta activation are being unfolded, limited information is available on the
      mechanisms that control its expression. Here, we report that in prostate cancer
      cells PKCdelta is tightly regulated by androgens at the transcriptional level.
      Steroid depletion from the culture medium causes a pronounced down-regulation of
      PKCdelta protein and mRNA in androgen-sensitive LNCaP prostate cancer cells, an
      effect that is rescued by the androgen R1881 in an androgen receptor (AR)
      dependent manner. Analysis of the PKCdelta promoter revealed a putative androgen
      responsive element (ARE) located 4.7 kb upstream from the transcription start
      site. Luciferase reporter assays show that this element is highly responsive to
      androgens, and mutations in key nucleotides in the AR-binding consensus abolish
      reporter activity. Furthermore, using chromatin immunoprecipitation assays, we
      determined that the AR binds in vivo to the PKCdelta ARE in response to androgen
      stimulation. Functional studies revealed that, notably, androgens modulate
      phorbol 12-myristate 13-acetate (PMA)-induced apoptosis in LNCaP cells, an effect
      that is dependent on PKCdelta. Indeed, androgen depletion or AR RNA interference
      severely impaired the apoptotic function of PKCdelta or the activation of p38, a
      downstream effector of PKCdelta in LNCaP cells--effects that can be rescued by
      restoring PKCdelta levels using an adenoviral delivery approach. Our studies
      identified a novel hormonal mechanism for the control of PKCdelta expression via
      transcriptional regulation that fine-tunes the magnitude of PKCdelta apoptotic
      responses.

PMID- 17178876
TI  - Endothelins induce CCR7 expression by breast tumor cells via endothelin receptor
      A and hypoxia-inducible factor-1.
AB  - Endothelin expression is increased in breast tumors and is associated with
      invasion and metastasis, whereas CCR7 expression by breast tumor cells may have a
      role in the organ specificity of breast cancer spread. In this article, we have
      analyzed whether endothelins influence breast tumor cell expression of the
      chemokine receptor CCR7. Stimulation of human breast tumor cell lines with
      endothelins increased cell surface expression of CCR7 via endothelin receptor A.
      The iron chelators desferrioxamine and cobalt chloride, which induce hypoxia
      inducible factor (HIF)-mediated transcription, also increased CCR7 expression;
      transfection of a dominant-negative version of the HIF regulatory subunit, HIF
      1alpha, into MCF-7 cells abolished CCR7 induction by endothelins, indicating that
      increased expression is due to HIF-1 stabilization. Endothelin stimulation
      promoted invasion toward the CCR7 ligands CCL19 and CCL21. Endothelin-mediated
      chemokine-independent invasion itself is dependent on CCR7 activity and could be
      abolished using a CCR7-neutralizing monoclonal antibody. In human breast
      carcinomas, mRNA expression of endothelins correlated with the level of CCR7
      expression, both of which were associated with the presence of lymph node
      metastases. Expression of the CCR7 ligands CCL19 and CCL21 was also higher in
      breast cancer patients with lymph node involvement compared with those without,
      but expression of these chemokines did not correlate with endothelin expression.
      These data show that CCR7 may be regulated by the breast tumor microenvironment
      and further support the use of endothelin receptor antagonists in the treatment
      of invasive and metastatic breast cancer.

PMID- 17178877
TI  - G-quadruplexes induce apoptosis in tumor cells.
AB  - Several G-rich oligodeoxynucleotides (ODNs), which are capable of forming G
      quadruplexes, have been shown to exhibit antiproliferative activity against tumor
      cell lines and antitumor activity in nude mice carrying prostate and breast tumor
      xenografts. However, the molecular basis for their antitumor activity remains
      unclear. In the current study, we showed that a variety of telomeric G-tail
      oligodeoxynucleotides (TG-ODNs) exhibited antiproliferative activity against many
      tumor cells in culture. Systematic mutational analysis of the TG-ODNs suggests
      that the antiproliferative activity depends on the G-quadruplex conformation of
      these TG-ODNs. TG-ODNs were also shown to induce poly(ADP-ribose) polymerase-1
      cleavage, phosphatidylserine flipping, and caspase activation, indicative of
      induction of apoptosis. TG-ODN-induced apoptosis was largely ataxia
      telangiectasia mutated (ATM) dependent. Furthermore, TG-ODN-induced apoptosis was
      inhibited by the c-Jun NH(2)-terminal kinase (JNK) inhibitor SP600125. Indeed, TG
      ODNs were shown to activate the JNK pathway in an ATM-dependent manner as
      evidenced by elevated phosphorylation of JNK and c-Jun. Interestingly, a number
      of G-quadruplex ODNs (GQ-ODN) derived from nontelomeric sequences also induced
      ATM/JNK-dependent apoptosis, suggesting a possible common mechanism of tumor cell
      killing by GQ-ODNs.

PMID- 17178878
TI  - Activation of p53 in cervical cancer cells by human papillomavirus E6 RNA
      interference is transient, but can be sustained by inhibiting endogenous nuclear
      export-dependent p53 antagonists.
AB  - p53 is degraded in cervical cancer cells by the human papillomavirus E6 and can
      be stabilized with short interfering RNA (siRNA) molecules targeting E6 mRNA. In
      this in vitro study, we show that E6 siRNA-induced p53 activation is transient in
      HeLa cervical cancer cells despite continuous suppression of E6 mRNA; activation
      can be sustained if the endogenous p53 antagonists COP1, MDM2, Pirh2, and c-Jun
      NH(2)-kinase are also targeted by siRNAs or by inhibiting the nuclear export of
      p53 with leptomycin B. The direct targeting of any one of these four cellular p53
      antagonists had no effect on p53 activity when E6 was intact, but inhibited the
      fading off of E6 siRNA-induced p53 activation in nonstress conditions. The effect
      was additive when multiple cellular antagonists were concomitantly inhibited,
      indicating that all these proteins degrade p53 when E6 is inactivated. The
      antiproliferative effect induced by E6 silencing was enhanced when the endogenous
      p53 antagonists were additionally targeted. In conclusion, if human
      papillomavirus E6 is inhibited under nonstress conditions, the subsequent p53
      activation is quickly reversed by the endogenous p53 degenerative machinery. The
      present results indicate that several cellular p53 antagonists must be inhibited
      for sustained p53 activity if E6 siRNA therapy is attempted and if no combined
      genotoxic therapy is applied.

PMID- 17178879
TI  - Proteomic profiling of primary breast cancer predicts axillary lymph node
      metastasis.
AB  - To determine if protein expression in primary breast cancers can predict axillary
      lymph node (ALN) metastasis, we assessed differences in protein expression
      between primary breast cancers with and without ALN metastasis using surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF
      MS). Laser capture microdissection was performed on invasive breast cancer frozen
      sections from 65 patients undergoing resection with sentinel lymph node (SLN) or
      level I and II ALN dissection. Isolated proteins from these tumors were applied
      to immobilized metal affinity capture (IMAC-3) ProteinChip arrays and analyzed by
      SELDI-TOF-MS to generate unique protein profiles. Correlations between unique
      protein peaks and histologically confirmed ALN status and other known
      clinicopathologic factors were examined using ANOVA and multivariate logistic
      regression. Two metal-binding polypeptides at 4,871 and 8,596 Da were identified
      as significant risk factors for nodal metastasis (P = 0.034 and 0.015,
      respectively) in a multivariate analysis. Lymphovascular invasion (LVI) was the
      only clinicopathologic factor predictive of ALN metastasis (P = 0.0038). In a
      logistic regression model combining the 4,871 and 8,596 Da peaks with LVI, the
      area under the receiver operating characteristic curve was 0.87. Compared with
      patients with negative ALN, those with > or =2 positive ALN or non-SLN metastases
      were significantly more likely to have an increased peak at 4,871 Da (P = 0.016
      and 0.0083, respectively). ProteinChip array analysis identified differential
      protein peaks in primary breast cancers that predict the presence and number of
      ALN metastases and non-SLN status.

PMID- 17178880
TI  - Cross-talk between G protein-coupled receptor and epidermal growth factor
      receptor signaling pathways contributes to growth and invasion of head and neck
      squamous cell carcinoma.
AB  - G protein-coupled receptors (GPCR) and the epidermal growth factor receptor
      (EGFR) are often both overexpressed and contribute to the growth of cancers by
      activating autocrine pathways. GPCR ligands have been reported to trigger EGFR
      signaling via receptor cross-talk in cancer cells. Here, we show that GPCR
      ligands prostaglandin E2 (PGE2) and bradykinin (BK) activate EGFR signaling.
      Inhibition of EGFR using several strategies, including small-molecule inhibitors
      and an EGFR-specific antibody, resulted in partial attenuation of signaling
      downstream of EGFR. PGE2 and BK triggered EGFR signaling by increasing selective
      autocrine release of transforming growth factor-alpha (TGF-alpha). Inhibition of
      tumor necrosis factor-alpha-converting enzyme abrogated BK- or PGE2-mediated
      activation of EGFR signaling. Both PGE2 and BK stimulated head and neck squamous
      cell carcinoma (HNSCC) invasion via EGFR. Treatment of HNSCC cells with the BK
      antagonist CU201 resulted in growth inhibition. The combination of CU201 with the
      EGFR small-molecule inhibitor erlotinib resulted in additive inhibitory effects
      on HNSCC cell growth in vitro. Inhibition of the PGE2 synthesis pathway with
      sulindac induced HNSCC cytotoxicity at high doses (EC(50), 620 micromol/L).
      However, combined inhibition of both EGFR with the tyrosine kinase inhibitor
      erlotinib and GPCR with sulindac at low doses of 6 and 310 micromol/L,
      respectively, resulted in synergistic killing of HNSCC tumor cells. Combined
      blockade of both EGFR and GPCRs may be a rational strategy to treat cancers,
      including HNSCC that shows cross-talk between GPCR and EGFR signaling pathways.

PMID- 17178881
TI  - Retargeted oncolytic measles strains entering via the EGFRvIII receptor maintain
      significant antitumor activity against gliomas with increased tumor specificity.
AB  - Among the best-characterized genetic alterations in gliomas is the amplification
      of the epidermal growth factor receptor (EGFR) gene, present in approximately 40%
      of glioblastoma multiforme, and frequently associated with the EGFRvIII gene
      rearrangement. We have previously shown that attenuated vaccine strains of
      measles virus have potent antitumor activity against gliomas, and identified H
      protein mutations, which ablate recognition of the natural measles virus
      receptors CD46 and SLAM. Retargeted recombinant viruses were generated from the
      measles Edmonston-NSe vaccine strain displaying a single-chain antibody against
      EGFRvIII at the COOH terminus of H and containing the marker green fluorescent
      protein (GFP) gene in position 1. Two different H mutants were employed: H(SNS)
      (V451S, Y481N, and A527S)-CD46 blind, and H(AA) (Y481A and R533A)-CD46 and SLAM
      blind. MV-GFP virus was used as a positive control. Both EGFRvIII-retargeted
      viruses had significant antitumor activity against EGFRvIII-expressing
      glioblastoma multiforme but no cytopathic effect against normal cells. In an
      orthotopic model of EGFRvIII-expressing GBM39 xenografts, there was comparable
      therapeutic efficacy between retargeted strains and unmodified MV-GFP and
      statistically significant prolongation of survival in treated animals compared
      with the control group (P = 0.001). Formation of syncytia was observed in tumors
      treated with retargeted viruses, with a surrounding infiltrate consisting of
      macrophages and natural killer cells. In summary, EGFRvIII-retargeted oncolytic
      measles virus strains have comparable therapeutic efficacy with the unmodified MV
      GFP strain against EGFRvIII-expressing glioma lines and xenografts with improved
      therapeutic index, a finding with potential translational implications in glioma
      virotherapy.

PMID- 17178882
TI  - Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and
      induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5.
AB  - Angiogenesis and signaling through the RAF/mitogen-activated
      protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have
      been reported to play important roles in the development of hepatocellular
      carcinomas (HCC). Sorafenib (BAY 43-9006, Nexavar) is a multikinase inhibitor
      with activity against Raf kinase and several receptor tyrosine kinases, including
      vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth
      factor receptor (PDGFR), FLT3, Ret, and c-Kit. In this study, we investigated the
      in vitro effects of sorafenib on PLC/PRF/5 and HepG2 HCC cells and the in vivo
      antitumor efficacy and mechanism of action on PLC/PRF/5 human tumor xenografts in
      severe combined immunodeficient mice. Sorafenib inhibited the phosphorylation of
      MEK and ERK and down-regulated cyclin D1 levels in these two cell lines.
      Sorafenib also reduced the phosphorylation level of eIF4E and down-regulated the
      antiapoptotic protein Mcl-1 in a MEK/ERK-independent manner. Consistent with the
      effects on both MEK/ERK-dependent and MEK/ERK-independent signaling pathways,
      sorafenib inhibited proliferation and induced apoptosis in both HCC cell lines.
      In the PLC/PRF/5 xenograft model, sorafenib tosylate dosed at 10 mg/kg inhibited
      tumor growth by 49%. At 30 mg/kg, sorafenib tosylate produced complete tumor
      growth inhibition. A dose of 100 mg/kg produced partial tumor regressions in 50%
      of the mice. In mechanism of action studies, sorafenib inhibited the
      phosphorylation of both ERK and eIF4E, reduced the microvessel area (assessed by
      CD34 immunohistochemistry), and induced tumor cell apoptosis (assessed by
      terminal deoxynucleotidyl transferase-mediated nick end labeling) in PLC/PRF/5
      tumor xenografts. These results suggest that the antitumor activity of sorafenib
      in HCC models may be attributed to inhibition of tumor angiogenesis (VEGFR and
      PDGFR) and direct effects on tumor cell proliferation/survival (Raf kinase
      signaling-dependent and signaling-independent mechanisms).

PMID- 17178883
TI  - Cross-talk between peroxisome proliferator-activated receptor delta and cytosolic
      phospholipase A(2)alpha/cyclooxygenase-2/prostaglandin E(2) signaling pathways in
      human hepatocellular carcinoma cells.
AB  - Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear
      transcription factor that is recently implicated in tumorigenesis besides lipid
      metabolism. This study describes the cross-talk between the PPARdelta and
      prostaglandin (PG) signaling pathways that coordinately regulate human
      hepatocellular carcinoma (HCC) cell growth. Activation of PPARdelta by its
      pharmacologic ligand, GW501516, enhanced the growth of three human HCC cell lines
      (HuH7, HepG2, and Hep3B), whereas inhibition of PPARdelta by small interfering
      RNA prevented growth. PPARdelta activation up-regulates the expression of
      cyclooxygenase (COX)-2, a rate-limiting enzyme for PG synthesis, and tumor
      growth. PPARdelta activation or PGE(2) treatment also induced the phosphorylation
      of cytosolic phospholipase A(2)alpha (cPLA(2)alpha), a key enzyme that releases
      arachidonic acid substrate for PG production via COX. Activation of cPLA(2)alpha
      by the calcium ionophore A23187 enhanced PPARdelta binding to PPARdelta response
      element (DRE) and increased PPARdelta reporter activity, which was blocked by the
      selective cPLA(2)alpha inhibitors. Consistent with this, addition of arachidonic
      acid to isolated nuclear extracts enhanced the binding of PPARdelta to DRE in
      vitro, suggesting a direct role of arachidonic acid for PPARdelta activation in
      the nucleus. Thus, PPARdelta induces COX-2 expression and the COX-2-derived
      PGE(2) further activates PPARdelta via cPLA(2)alpha. Such an interaction forms a
      novel feed-forward growth-promoting signaling that may play a role in
      hepatocarcinogenesis.

PMID- 17178885
TI  - Cationic albumin-conjugated pegylated nanoparticles allow gene delivery into
      brain tumors via intravenous administration.
AB  - Patients with malignant gliomas have a poor prognosis because these tumors do not
      respond well to conventional treatments. Studies of glioma xenografts suggest
      that they may be amenable to gene therapy with cytotoxic genes, such as the
      proapoptotic Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand
      (Apo2L/TRAIL). Gene therapy of gliomas ideally employs i.v. given vectors, thus
      excluding viral vectors as they cannot cross the brain microvascular endothelium
      or blood-brain barrier. Recently, we reported the synthesis of cationic albumin
      conjugated pegylated nanoparticles (CBSA-NP) and showed their accumulation in
      mouse brain cells upon i.v. administration. In this study, plasmid pORF-hTRAIL
      (pDNA) was incorporated into CBSA-NP, and the resulting CBSA-NP-hTRAIL was
      evaluated as a nonviral vector for gene therapy of gliomas. Thirty minutes after
      transfection of C6 glioma cells, CBSA-NP-hTRAIL was internalized and mostly
      located in the cytoplasm, whereas NP-hTRAIL was entrapped in the endolysosomal
      compartment. At 6 and 48 hours after transfection, respectively, released pDNA
      was present in the nuclei and induced apoptosis. At 30 minutes after i.v.
      administration of CBSA-NP-hTRAIL to BALB/c mice bearing i.c. C6 gliomas, CBSA-NP
      hTRAIL colocalized with glycoproteins in brain and tumor microvasculature and,
      via absorptive-mediated transcytosis, accumulated in tumor cells. At 24 and 48
      hours after i.v. administration of CBSA-NP-hTRAIL, respectively, hTRAIL mRNA and
      protein were detected in normal brain and tumors. Furthermore, repeated i.v.
      injections of CBSA-NP-hTRAIL induced apoptosis in vivo and significantly delayed
      tumor growth. In summary, this study indicates that CBSA-NP-hTRAIL is a promising
      candidate for noninvasive gene therapy of malignant glioma.

PMID- 17178884
TI  - N-glycosylation of MDA-7/IL-24 is dispensable for tumor cell-specific apoptosis
      and "bystander" antitumor activity.
AB  - Biochemical and genetic mutation-based analyses confirm that the MDA-7/IL-24
      protein can induce transformed cell-specific apoptosis through a mechanism
      involving endoplasmic reticulum (ER) stress-associated pathways. Covalent
      modifications by N-linked glycans in the ER contribute to the conformational
      maturation and biological functions of many proteins. Because MDA-7/IL-24 is a
      glycosylated protein, we investigated the role of glycosylation in mediating the
      specific biological and "bystander" antitumor activities of this cytokine. An
      adenovirus vector expressing a nonsecreted and nonglycosylated version of MDA
      7/IL-24 protein was generated via deletion of its signal peptide and point
      mutations of its three N-glycosylated sites. In this study, we showed that this
      intracellular nonglycosylated protein was as effective as wild-type MDA-7/IL-24
      protein in inducing apoptosis in multiple tumor cell lines. Both constructs (a)
      displayed transformed cell specificity and localization to the ER compartment,
      (b) mediated apoptosis through JAK/STAT-independent and p38(MAPK)-dependent
      pathways, (c) induced sustained ER stress as evidenced by expression of ER stress
      markers (BiP/GRP78, GRP94, XBP-1, and eIF2alpha), and (d) generated proteins that
      physically interacted with BiP/GRP78. Additionally, an expression construct
      containing the mda-7/IL-24 signal peptide linked to the mutated nonglycosylated
      mda-7/IL-24 gene retained the ability to induce bystander antitumor activity.
      These studies reveal that MDA-7/IL-24 glycosylation is not mandatory for inducing
      cell death or bystander activities in different cancer cells, providing new
      insights into the mechanism by which MDA-7/IL-24 induces apoptosis and ER stress.

PMID- 17178886
TI  - Dimethylfumarate impairs melanoma growth and metastasis.
AB  - Dimethylfumarate (DMF) inhibits signals transmitted by Rel proteins and is used
      for the treatment of inflammatory skin diseases such as psoriasis, but potential
      effects of DMF on tumor progression have yet not been analyzed. We show that DMF
      reduced melanoma growth and metastasis in severe combined immunodeficient mouse
      models. To identify targets of DMF action, we analyzed mRNA expression in DMF
      treated melanomas by gene chip arrays. Using BiblioSphere software for data
      analysis, significantly regulated genes were mapped to Gene Ontology terms cell
      death, cell growth, and cell cycle. Indeed, we found that DMF inhibited
      proliferation of human melanoma cells A375 and M24met in vitro. The cell cycle
      was arrested at the G(2)-M boundary. Moreover, DMF was proapoptotic, as shown by
      cell cycle analysis and by Annexin V and Apo2.7 staining. These results were
      confirmed in vivo. DMF reduced proliferation rates of tumor cells as assessed by
      Ki-67 immunostaining and increased apoptosis as assessed by terminal
      deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining. In
      conclusion, DMF is antiproliferative and proapoptotic and reduces melanoma growth
      and metastasis in animal models.

PMID- 17178887
TI  - Elevated E2F1 inhibits transcription of the androgen receptor in metastatic
      hormone-resistant prostate cancer.
AB  - Activation of E2F transcription factors, through disruption of the retinoblastoma
      (Rb) tumor-suppressor gene, is a key event in the development of many human
      cancers. Previously, we showed that homozygous deletion of Rb in a prostate
      tissue recombination model exhibits increased E2F activity, activation of E2F
      target genes, and increased susceptibility to hormonal carcinogenesis. In this
      study, we examined the expression of E2F1 in 667 prostate tissue cores and
      compared it with the expression of the androgen receptor (AR), a marker of
      prostate epithelial differentiation, using tissue microarray analysis. We show
      that E2F1 expression is low in benign and localized prostate cancer, modestly
      elevated in metastatic lymph nodes from hormone-naive patients, and significantly
      elevated in metastatic tissues from hormone-resistant prostate cancer patients (P
      = 0.0006). In contrast, strong AR expression was detected in benign prostate
      (83%), localized prostate cancer (100%), and lymph node metastasis (80%), but
      decreased to 40% in metastatic hormone-resistant prostate cancer (P = 0.004).
      Semiquantitative reverse transcription-PCR analysis showed elevated E2F1 mRNA
      levels and increased levels of the E2F-target genes dihyrofolate reductase and
      proliferating cell nuclear antigen in metastatic hormone-independent prostate
      cancer cases compared with benign tissues. To identify a role of E2F1 in hormone
      independent prostate cancer, we examined whether E2F1 can regulate AR expression.
      We show that exogenous expression of E2F1 significantly inhibited AR mRNA and AR
      protein levels in prostate epithelial cells. E2F1 also inhibited an AR promoter
      luciferase construct that was dependent on the transactivation domain of E2F1.
      Furthermore, using chromatin immunoprecipitation assays, we show that E2F1 and
      the pocket protein family members p107 and p130 bind to the AR promoter in vivo.
      Taken together, these results show that elevated E2F1, through its ability to
      repress AR transcription, may contribute to the progression of hormone
      independent prostate cancer.

PMID- 17178888
TI  - Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells.
AB  - Lung cancer is the leading cause of cancer death among both men and women. Only
      approximately 15% of people diagnosed with non-small cell lung cancer (NSCLC)
      survive this disease beyond 5 years. Thus, novel therapeutic strategies are
      urgently needed to improve the clinical management of this devastating disease.
      We have previously shown the antiproliferative effect of MBP-1 on several human
      cancer cells. In this study, we have examined the potential of MBP-1 as a gene
      therapeutic candidate in regression of non-small cell lung tumor growth. We have
      observed that exogenous expression of MBP-1 in NSCLC cells (H1299) induces
      massive cell death. To determine the gene therapeutic potential of MBP-1,
      replication-deficient recombinant adenovirus expressing MBP-1 was given
      intratumorally in human lung cancer xenografts in nude mice. Our results showed a
      significant regression of lung tumor growth and prolonged survival on treatment
      with MBP-1 compared with the control groups (saline or dl312). Subsequently, the
      mechanism of MBP-1-mediated H1299 cell death was investigated. Our results
      suggested that MBP-1 induced poly(ADP-ribose) polymerase cleavage in H1299 cells;
      however, treatment with pan-caspase inhibitor did not protect against MBP-1
      induced cell death. Cells transduced with MBP-1 displayed early plasma membrane
      permeability, mitochondrial damage without cytochrome c release, and extensive
      cytoplasmic vacuolation, yielding a morphotype that is typical of necrosis. Taken
      together, this study suggests that MBP-1 expression induces a novel form of
      necrosis-like cell death and MBP-1 could be a potential gene therapeutic
      candidate against non-small cell lung tumor growth.

PMID- 17178889
TI  - Dendrimer-encapsulated camptothecins: increased solubility, cellular uptake, and
      cellular retention affords enhanced anticancer activity in vitro.
AB  - A biocompatible polyester dendrimer composed of the natural metabolites, glycerol
      and succinic acid, is described for the encapsulation of the antitumor
      camptothecins, 10-hydroxycamptothecin and 7-butyl-10-aminocamptothecin. The
      cytotoxicity of the dendrimer-drug complex toward four different human cancer
      cell lines [human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT
      29), non-small cell lung carcinoma (NCI-H460), and glioblastoma (SF-268)] is also
      reported, and low nmol/L IC(50) values are measured. Cellular uptake and efflux
      measurements in MCF-7 cells show an increase of 16-fold for cellular uptake and
      an increase in drug retention within the cell when using the dendrimer vehicle.

PMID- 17178890
TI  - A novel pathway involving melanoma differentiation associated gene-7/interleukin
      24 mediates nonsteroidal anti-inflammatory drug-induced apoptosis and growth
      arrest of cancer cells.
AB  - Numerous studies show that nonsteroidal anti-inflammatory drugs (NSAIDs) are
      effective in chemoprevention or treatment of cancer. Nevertheless, the mechanisms
      underlying these antineoplastic effects remain poorly understood. Here, we report
      that induction of the cancer-specific proapoptotic cytokine melanoma
      differentiation associated gene-7/interleukin-24 (MDA-7/IL-24) by several NSAIDs
      is an essential step for induction of apoptosis and G(2)-M growth arrest in
      cancer cells in vitro and inhibition of tumor growth in vivo. We also show that
      MDA-7/IL-24-dependent up-regulation of growth arrest and DNA damage inducible 45
      alpha (GADD45alpha) and GADD45gamma gene expression is sufficient for cancer cell
      apoptosis via c-Jun NH(2)-terminal kinase (JNK) activation and growth arrest
      induction through inhibition of Cdc2-cyclin B checkpoint kinase. Knockdown of
      GADD45alpha and GADD45gamma transcription by small interfering RNA abrogates
      apoptosis and growth arrest induction by the NSAID treatment, blocks JNK
      activation, and restores Cdc2-cyclin B kinase activity. Our results establish MDA
      7/IL-24 and GADD45alpha and GADD45gamma as critical mediators of apoptosis and
      growth arrest in response to NSAIDs in cancer cells.

PMID- 17178892
TI  - DNA damage by benzo(a)pyrene in human cells is increased by cigarette smoke and
      decreased by a filter containing rosemary extract, which lowers free radicals.
AB  - We found previously that the human lung benzo(a)pyrene (BP)-7,8-diol-9,10-epoxide
      N(2)-deoxyguanosine (BPDE-dG) adduct concentrate in the target bronchial cells.
      This adduct is now considered to be critical event in tumorigenesis by BP. In
      this study, we investigate the contribution of cigarette smoke on the BPDE-dG
      formation. In a cell-free system, the amount of (-)-anti-BPDE-dG adduct increased
      linearly with concentration of cigarette smoke in the presence of (+)-BP-7,8
      diol. Catalase and superoxide dismutase inhibited its formation by >80%. When MCF
      7 cells were treated for 2 hours with the (+)-BP-7,8-diol, cigarette smoke
      increased dose dependently the formation of (-)-anti-BPDE-dG and decreased the
      cytochrome P450 (CYP)-dependent formation of (+)-r-7,t-8-dihydroxy-c-9,10-oxy
      7,8,9,10-tetrahydro-BP the adduct. Then, cells were treated for up to 1 day with
      BP and then exposed for 2 hours with cigarette smoke. During these 2 hours, there
      are twice the increase in the adduct formation in cells treated with cigarette
      smoke compared with levels in nontreated cells due to CYP activity. Thus,
      cigarette smoke containing reactive oxygen species may activate the second step
      of BP metabolic way, leading to the formation of BPDE-dG adduct. Cigarette smoke
      thus seems may be in part responsible for the formation of the critical lung
      tumorigenic adduct. Finally, modified cigarette filter containing rosemary
      extract decreases by >70% of the BPDE-dG adducts level due to the cigarette smoke
      in MCF-7 cells. This approach may lead to decreasing lung cancer risk in addicted
      smokers.

PMID- 17178891
TI  - Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both
      yeast and mammalian cells.
AB  - To elucidate the mechanism of acquired resistance to Adriamycin, we searched for
      genes that, when overexpressed, render Saccharomyces cerevisiae resistant to
      Adriamycin. We identified AKL1, a gene of which the function is unknown but is
      considered, nonetheless, to be a member of the Ark/Prk kinase family, which is
      involved in the regulation of endocytosis, on the basis of its deduced amino acid
      sequence. Among tested members of the Ark/Prk kinase family (Ark1, Prk1, and
      Akl1), overexpressed Prk1 also conferred Adriamycin resistance on yeast cells.
      Prk1 is known to dissociate the Sla1/Pan1/End3 complex, which is involved in
      endocytosis, by phosphorylating Sla1 and Pan1 in the complex. We showed that Akl1
      promotes phosphorylation of Pan1 in this complex and reduces the endocytic
      ability of the cell, as does Prk1. Sla1- and End3-defective yeast cells were also
      resistant to Adriamycin and overexpression of Akl1 in these defective cells did
      not increase the degree of Adriamycin resistance, suggesting that Akl1 might
      reduce Adriamycin toxicity by reducing the endocytic ability of cells via a
      mechanism that involves the Sla1/Pan1/End3 complex and the phosphorylation of
      Pan1. We also found that HEK293 cells that overexpressed AAK1, a member of the
      human Ark/Prk family, were Adriamycin resistant. Our findings suggest that
      endocytosis might be involved in the mechanism of Adriamycin toxicity in yeast
      and human cells.

PMID- 17178893
TI  - Therapeutic expression of an anti-death receptor 5 single-chain fixed-variable
      region prevents tumor growth in mice.
AB  - The clinical use of the single-chain fixed-variable (scFv) fragments of
      recombinant monoclonal antibodies as credible alternatives for classic
      therapeutic antibodies has two limitations: rapid blood clearance and inefficient
      local expression of functional molecules. In attempt to address these issues, we
      have developed a novel gene therapy protocol in which the anti-death receptor 5
      (DR5) scFv fragments were either in vitro expressed in several tumor cell lines,
      or in vivo expressed in mice, using recombinant adeno-associated virus (rAAV)
      mediated gene transfer. Viral transduction using the rAAV-S3C construct, which
      encodes a scFv molecule (S3C scFv) specific to DR5, led to stable expression in
      tumor cell lines and showed apoptosis-inducing activity in vitro, which could be
      inhibited by recombinant DR5 but not by DR4. A single i.m. injection of rAAV-S3C
      virus in nude mice resulted in stable expression of DR5-binding S3C scFv proteins
      in mouse sera for at least 240 days. Moreover, the expression of S3C scFv was
      associated with significant suppression of tumor growth and the increase of tumor
      cell apoptosis in previously established s.c. human lung LTEP-sml and liver Hep3B
      tumor xenografts.

PMID- 17178894
TI  - Diverse gene expression and DNA methylation profiles correlate with differential
      adaptation of breast cancer cells to the antiestrogens tamoxifen and fulvestrant.
AB  - The development of targeted therapies for antiestrogen-resistant breast cancer
      requires a detailed understanding of its molecular characteristics. To further
      elucidate the molecular events underlying acquired resistance to the
      antiestrogens tamoxifen and fulvestrant, we established drug-resistant sublines
      from a single colony of hormone-dependent breast cancer MCF7 cells. These model
      systems allowed us to examine the cellular and molecular changes induced by
      antiestrogens in the context of a uniform clonal background. Global changes in
      both basal and estrogen-induced gene expression profiles were determined in
      hormone-sensitive and hormonal-resistant sublines using Affymetrix Human Genome
      U133 Plus 2.0 Arrays. Changes in DNA methylation were assessed by differential
      methylation hybridization, a high-throughput promoter CpG island microarray
      analysis. By comparative studies, we found distinct gene expression and promoter
      DNA methylation profiles associated with acquired resistance to fulvestrant
      versus tamoxifen. Fulvestrant resistance was characterized by pronounced up
      regulation of multiple growth-stimulatory pathways, resulting in estrogen
      receptor alpha (ERalpha)-independent, autocrine-regulated proliferation.
      Conversely, acquired resistance to tamoxifen correlated with maintenance of the
      ERalpha-positive phenotype, although receptor-mediated gene regulation was
      altered. Activation of growth-promoting genes, due to promoter hypomethylation,
      was more frequently observed in antiestrogen-resistant cells compared with gene
      inactivation by promoter hypermethylation, revealing an unexpected insight into
      the molecular changes associated with endocrine resistance. In summary, this
      study provides an in-depth understanding of the molecular changes specific to
      acquired resistance to clinically important antiestrogens. Such knowledge of
      resistance-associated mechanisms could allow for identification of therapy
      targets and strategies for resensitization to these well-established antihormonal
      agents.

PMID- 17178895
TI  - Mammary-specific Ron receptor overexpression induces highly metastatic mammary
      tumors associated with beta-catenin activation.
AB  - Activated growth factor receptor tyrosine kinases (RTK) play pivotal roles in a
      variety of human cancers, including breast cancer. Ron, a member of the Met RTK
      proto-oncogene family, is overexpressed or constitutively active in 50% of human
      breast cancers. To define the significance of Ron overexpression and activation
      in vivo, we generated transgenic mice that overexpress a wild-type or
      constitutively active Ron receptor in the mammary epithelium. In these animals,
      Ron expression is significantly elevated in mammary glands and leads to a
      hyperplastic phenotype by 12 weeks of age. Ron overexpression is sufficient to
      induce mammary transformation in all transgenic animals and is associated with a
      high degree of metastasis, with metastatic foci detected in liver and lungs of
      >86% of all transgenic animals. Furthermore, we show that Ron overexpression
      leads to receptor phosphorylation and is associated with elevated levels of
      tyrosine phosphorylated beta-catenin and the up-regulation of genes, including
      cyclin D1 and c-myc, which are associated with poor prognosis in patients with
      human breast cancers. These studies suggest that Ron overexpression may be a
      causative factor in breast tumorigenesis and provides a model to dissect the
      mechanism by which the Ron induces transformation and metastasis.

PMID- 17178896
TI  - Peroxisome proliferator-activated receptor gamma is a Zac target gene mediating
      Zac antiproliferation.
AB  - Zac is a C2H2 zinc finger protein, which regulates apoptosis and cell cycle
      arrest through DNA binding and transactivation. During tumorigenesis and in
      response to mitogenic activation, Zac gene expression is down-regulated in a
      methylation-sensitive manner. As yet, no target genes have been identified that
      could explain the potent antiproliferative function of Zac. Here, applying genome
      wide expression analysis, we identify peroxisome proliferator-activated receptor
      gamma (PPARgamma) as a new bona fide Zac target gene, which is induced by direct
      Zac binding to the proximal PPARgamma1 promoter. We show that in human colon
      carcinoma cells, ZAC activates expression of PPARgamma target genes in a
      PPARgamma-dependent manner. Moreover, we show that treatment of pituitary tumor
      cells with octreotide, a somatostatin analogue, leads to Zac induction and
      subsequent Zac-dependent up-regulation of PPARgamma, which thereupon mediates
      part of the antiproliferative activity of Zac. Our work provides a first step
      toward elucidating a functional relationship between Zac and PPARgamma that could
      be relevant to the understanding of tumorigenesis and diabetes as well.

PMID- 17178897
TI  - The tumor metastasis suppressor gene Drg-1 down-regulates the expression of
      activating transcription factor 3 in prostate cancer.
AB  - The tumor metastasis suppressor gene Drg-1 has been shown to suppress metastasis
      without affecting tumorigenicity in immunodeficient mouse models of prostate and
      colon cancer. Expression of Drg-1 has also been found to have a significant
      inverse correlation with metastasis or invasiveness in various types of human
      cancer. However, how Drg-1 exerts its metastasis suppressor function remains
      unknown. In the present study, to elucidate the mechanism of action of the Drg-1
      gene, we did a microarray analysis and found that induction of Drg-1
      significantly inhibited the expression of activating transcription factor (ATF)
      3, a member of the ATF/cyclic AMP-responsive element binding protein family of
      transcription factors. We also showed that Drg-1 attenuated the endogenous level
      of ATF3 mRNA and protein in prostate cancer cells, whereas Drg-1 small
      interfering RNA up-regulated the ATF3 expression. Furthermore, Drg-1 suppressed
      the promoter activity of the ATF3 gene, indicating that Drg-1 regulates ATF3
      expression at the transcriptional level. Our immunohistochemical analysis on
      prostate cancer specimens revealed that nuclear expression of ATF3 was inversely
      correlated to Drg-1 expression and positively correlated to metastases.
      Consistently, we have found that ATF3 overexpression promoted invasiveness of
      prostate tumor cells in vitro, whereas Drg-1 suppressed the invasive ability of
      these cells. More importantly, overexpression of ATF3 in prostate cancer cells
      significantly enhanced spontaneous lung metastasis of these cells without
      affecting primary tumorigenicity in a severe combined immunodeficient mouse
      model. Taken together, our results strongly suggest that Drg-1 suppresses
      metastasis of prostate tumor cells, at least in part, by inhibiting the invasive
      ability of the cells via down-regulation of the expression of the ATF3 gene.

PMID- 17178898
TI  - Antitumor effect of 2-methoxyestradiol in a rat orthotopic brain tumor model.
AB  - Grade 4 malignant glioma (GBM) is a fatal disease despite aggressive surgical and
      adjuvant therapies. The hallmark of GBM tumors is the presence of
      pseudopalisading necrosis and microvascular proliferation. These tumor cells are
      hypoxic and express hypoxia-inducible factor-1 (HIF-1), a prosurvival
      transcription factor that promotes formation of neovasculature through activation
      of target genes, such as vascular endothelial growth factor. Here, we evaluated
      whether 2-methoxyestradiol, a microtubule and HIF-1 inhibitor, would have
      therapeutic potential for this disease in a 9L rat orthotopic gliosarcoma model
      using a combination of noninvasive imaging methods: magnetic resonance imaging to
      measure the tumor volume and bioluminescence imaging for HIF-1 activity. After
      imaging, histologic data were subsequently evaluated to elucidate the drug action
      mechanism in vivo. Treatment with 2-methoxyestradiol (60-600 mg/kg/d) resulted in
      a dose-dependent inhibition of tumor growth. This effect was also associated with
      improved tumor oxygenation as assessed by pimonidazole staining, decreased HIF
      1alpha protein levels, and microtubule destabilization as assessed by
      deacetylation. Our results indicate that 2-methoxyestradiol may be a promising
      chemotherapeutic agent for the treatment of malignant gliomas, with significant
      growth inhibition. Further studies are needed to assess the effect of low or
      intermediate doses of 2-methoxyestradiol in combination with chemotherapeutic
      agents in clinical studies focused on malignant gliomas. In addition to showing
      tumor growth inhibition, we identified three potential surrogate biomarkers to
      determine the efficacy of 2-methoxyestradiol therapy: decreased HIF-1alpha
      levels, alpha-tubulin acetylation, and degree of hypoxia as determined by
      pimonidazole staining.

PMID- 17178900
TI  - Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in
      human breast cells using oligonucleotide arrays.
AB  - Retinoids have been found to be promising chemopreventive agents that play an
      important role in regulating cell growth, differentiation, and apoptosis. The
      action of retinoids is mediated by retinoid receptors (retinoic acid receptors
      and retinoid X receptors), which are nuclear transcription factors that, when
      bound to retinoids, regulate gene expression. LGD1069 is a highly selective RXR
      agonist that has reduced toxicity compared with retinoids. Our previous studies
      have shown that RXR-selective ligands (or "rexinoids"), including LGD1069, can
      inhibit the growth of normal and malignant breast cells and can suppress the
      development of breast cancer in transgenic mice. For the current study, we
      attempted to identify biomarkers of the chemopreventive effect of the RXR
      selective retinoid LGD1069. In these experiments, we used Affymetrix microarrays
      to identify target genes that were modulated by LGD1069 in normal human breast
      cells. Affymetrix and dChip analysis identified more than 100 genes that were up
      regulated or down-regulated by LGD1069 treatment. We then tested 16 of these
      genes in validation experiments using quantitative reverse transcription-PCR and
      Western blotting of independently prepared samples, and found that 15 of 16 genes
      were modulated in a similar manner in these validation experiments as in the
      microarray experiments. Genes found to be regulated include known retinoid
      regulated genes, growth regulatory genes, transcription factors, and
      differentiation markers. We then showed that the expression of several of these
      rexinoid-regulated biomarkers is modulated in vivo in mammary glands from mice
      treated with LGD1069. These critical growth-regulating proteins will be promising
      targets of future agents for the prevention and treatment of breast cancer.

PMID- 17178899
TI  - Mitogenic action of the androgen receptor sensitizes prostate cancer cells to
      taxane-based cytotoxic insult.
AB  - Prostate cancer cells are dependent on androgen for growth and survival; as such,
      inhibition of androgen receptor (AR) activity is the first line of intervention
      for disseminated disease. Recently, specific cytotoxic agents have been shown to
      extend survival times in patients with advanced disease. Given the established
      ability of androgen to modify cell survival in prostate cancer cells, it is
      imperative to determine the effect of the hormonal environment on cytotoxic
      response. Here, we show that the response of prostate cancer cells to taxane
      induced cell death is significantly enhanced by androgen stimulation in AR
      positive, androgen-dependent prostate cancer cells. Similar results were observed
      on androgen-independent AR activation. By contrast, AR-positive yet androgen
      independent or AR-negative cells were refractory to androgen influence on taxane
      function. The ability of androgen to potentiate taxane activity was dependent on
      its mitogenic capacity and was separable from overall AR activity, as
      coadministration of AR antagonists, G(1) cyclin-dependent kinase inhibitors, or
      high-dose (growth inhibitory) androgen nullified the proapoptotic function of
      androgen. Observed induction of cell death was attributed to caspase-dependent
      apoptosis and correlated with p53 activation. Combined, these data indicate that
      the cytotoxic effects of taxanes are substantially influenced by the hormonal
      environment and/or status of AR activity in prostate cancer cells and provide the
      foundation for refinement and optimization of cytotoxic intervention in prostate
      cancer.

PMID- 17178901
TI  - A systematic assessment of common genetic variation in CYP11A and risk of breast
      cancer.
AB  - CYP11A catalyzes the rate-limiting step in the biosynthesis of sex-steroid
      hormones. In this study, we employed a systematic approach that involved gene
      resequencing and a haplotype-based analysis to investigate the relationship
      between common variation in CYP11A and breast cancer risk among African
      Americans, Latinas, Japanese-Americans, Native Hawaiians, and Whites in the
      Multiethnic Cohort Study. Resequencing in a multiethnic panel of 95 advanced
      breast cancer cases revealed no common missense variant (> or =5% frequency).
      Common haplotype patterns were assessed by genotyping 36 densely spaced single
      nucleotide polymorphisms (SNPs) spanning 67 kb of the CYP11A locus in a
      multiethnic panel of subjects (n = 349; 1 SNP/1.86 kb on average). We identified
      one to two regions of strong linkage disequilibrium in these populations. Twelve
      tagging SNPs were selected to predict the common haplotypes (> or =5% frequency)
      in these regions with high probability (average R(h)(2) = 0.94) and were examined
      in a breast cancer case-control study in the Multiethnic Cohort Study (1,615
      cases and 1,962 controls). A global test for differences in risk according to
      common haplotypes over the locus was statistically significant (P = 0.006), as
      were associations with haplotypes in each block (block 1 global test, P = 0.008;
      haplotype 1D, effect per haplotype copy, odds ratios, 1.23; 95% confidence
      interval, 1.03-1.48) and block 2 (global test, P = 0.016; haplotype 2F odds
      ratios, 1.52; 95% confidence interval, 1.15-2.01). These haplotypes were most
      common in Japanese-Americans and Native Hawaiians, followed by Whites then
      Latinas, and were rare in African-Americans (<5% frequency); the haplotype
      effects on risk across each group were homogeneous. Based on these findings,
      CYP11A deserves further consideration as a candidate breast cancer susceptibility
      gene.

PMID- 17178903
TI  - Howard Earle Skipper: in memoriam (1915-2006).

PMID- 17178902
TI  - Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus
      bisporus).
AB  - White button mushrooms (Agaricus bisporous) are a potential breast cancer
      chemopreventive agent, as they suppress aromatase activity and estrogen
      biosynthesis. Therefore, we evaluated the activity of mushroom extracts in the
      estrogen receptor-positive/aromatase-positive MCF-7aro cell line in vitro and in
      vivo. Mushroom extract decreased testosterone-induced cell proliferation in MCF
      7aro cells but had no effect on MCF-10A, a nontumorigenic cell line. Most potent
      mushroom chemicals are soluble in ethyl acetate. The major active compounds found
      in the ethyl acetate fraction are unsaturated fatty acids such as linoleic acid,
      linolenic acid, and conjugated linoleic acid. The interaction of linoleic acid
      and conjugated linoleic acid with aromatase mutants expressed in Chinese hamster
      ovary cells showed that these fatty acids inhibit aromatase with similar potency
      and that mutations at the active site regions affect its interaction with these
      two fatty acids. Whereas these results suggest that these two compounds bind to
      the active site of aromatase, the inhibition kinetic analysis indicates that they
      are noncompetitive inhibitors with respect to androstenedione. Because only
      conjugated linoleic acid was found to inhibit the testosterone-dependent
      proliferation of MCF-7aro cells, the physiologically relevant aromatase
      inhibitors in mushrooms are most likely conjugated linoleic acid and its
      derivatives. The in vivo action of mushroom chemicals was shown using nude mice
      injected with MCF-7aro cells. The studies showed that mushroom extract decreased
      both tumor cell proliferation and tumor weight with no effect on rate of
      apoptosis. Therefore, our studies illustrate the anticancer activity in vitro and
      in vivo of mushroom extract and its major fatty acid constituents.

PMID- 17178904
TI  - Joseph H. Burchenal: in memoriam (1912-2006).

PMID- 17178905
TI  - Making more microtubules by severing: a common theme of noncentrosomal
      microtubule arrays?
AB  - Two related enzymes, katanin and spastin, use the energy from ATP hydrolysis to
      sever microtubules. Two new studies (one in this issue; see McNally et al., p.
      881) show that microtubule severing by katanin provides a means for increasing
      microtubule density in meiotic spindles. Interestingly, loss of spastin leads to
      a sparser microtubule array in axons and synaptic boutons. Together, these
      studies hint at a wider role for microtubule-severing enzymes in the formation
      and organization of noncentrosomal microtubule arrays by generating new seeds for
      microtubule growth.

PMID- 17178906
TI  - p14-MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation
      during tissue homeostasis.
AB  - The extracellular signal-regulated kinase (ERK) cascade regulates proliferation,
      differentiation, and survival in multicellular organisms. Scaffold proteins
      regulate intracellular signaling by providing critical spatial and temporal
      specificity. The scaffold protein MEK1 (mitogen-activated protein kinase and ERK
      kinase 1) partner (MP1) is localized to late endosomes by the adaptor protein
      p14. Using conditional gene disruption of p14 in mice, we now demonstrate that
      the p14-MP1-MEK1 signaling complex regulates late endosomal traffic and cellular
      proliferation. This function its essential for early embryogenesis and during
      tissue homeostasis, as revealed by epidermis-specific deletion of p14. These
      findings show that endosomal p14-MP1-MEK1 signaling has a specific and essential
      function in vivo and, therefore, indicate that regulation of late endosomal
      traffic by extracellular signals is required to maintain tissue homeostasis.

PMID- 17178907
TI  - Katanin controls mitotic and meiotic spindle length.
AB  - Accurate control of spindle length is a conserved feature of eukaryotic cell
      division. Lengthening of mitotic spindles contributes to chromosome segregation
      and cytokinesis during mitosis in animals and fungi. In contrast, spindle
      shortening may contribute to conservation of egg cytoplasm during female meiosis.
      Katanin is a microtubule-severing enzyme that is concentrated at mitotic and
      meiotic spindle poles in animals. We show that inhibition of katanin slows the
      rate of spindle shortening in nocodazole-treated mammalian fibroblasts and in
      untreated Caenorhabditis elegans meiotic embryos. Wild-type C. elegans meiotic
      spindle shortening proceeds through an early katanin-independent phase marked by
      increasing microtubule density and a second, katanin-dependent phase that occurs
      after microtubule density stops increasing. In addition, double-mutant analysis
      indicated that gamma-tubulin-dependent nucleation and microtubule severing may
      provide redundant mechanisms for increasing microtubule number during the early
      stages of meiotic spindle assembly.

PMID- 17178908
TI  - Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+
      channels.
AB  - The voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane
      mediates metabolic flow, Ca(2+), and cell death signaling between the endoplasmic
      reticulum (ER) and mitochondrial networks. We demonstrate that VDAC1 is
      physically linked to the endoplasmic reticulum Ca(2+)-release channel inositol
      1,4,5-trisphosphate receptor (IP(3)R) through the molecular chaperone glucose
      regulated protein 75 (grp75). Functional interaction between the channels was
      shown by the recombinant expression of the ligand-binding domain of the IP(3)R on
      the ER or mitochondrial surface, which directly enhanced Ca(2+) accumulation in
      mitochondria. Knockdown of grp75 abolished the stimulatory effect, highlighting
      chaperone-mediated conformational coupling between the IP(3)R and the
      mitochondrial Ca(2+) uptake machinery. Because organelle Ca(2+) homeostasis
      influences fundamentally cellular functions and death signaling, the central
      location of grp75 may represent an important control point of cell fate and
      pathogenesis.

PMID- 17178909
TI  - Recruitment of Atg9 to the preautophagosomal structure by Atg11 is essential for
      selective autophagy in budding yeast.
AB  - Autophagy is a conserved degradative pathway that is induced in response to
      various stress and developmental conditions in eukaryotic cells. It allows the
      elimination of cytosolic proteins and organelles in the lysosome/vacuole. In the
      yeast Saccharomyces cerevisiae, the integral membrane protein Atg9 (autophagy
      related protein 9) cycles between mitochondria and the preautophagosomal
      structure (PAS), the nucleating site for formation of the sequestering vesicle,
      suggesting a role in supplying membrane for vesicle formation and/or expansion
      during autophagy. To better understand the mechanisms involved in Atg9 cycling,
      we performed a yeast two-hybrid-based screen and identified a peripheral membrane
      protein, Atg11, that interacts with Atg9. We show that Atg11 governs Atg9 cycling
      through the PAS during specific autophagy. We also demonstrate that the integrity
      of the actin cytoskeleton is essential for correct targeting of Atg11 to the PAS.
      We propose that a pool of Atg11 mediates the anterograde transport of Atg9 to the
      PAS that is dependent on the actin cytoskeleton during yeast vegetative growth.

PMID- 17178910
TI  - Rac1 and a GTPase-activating protein, MgcRacGAP, are required for nuclear
      translocation of STAT transcription factors.
AB  - STAT transcription factors are tyrosine phosphorylated upon cytokine stimulation
      and enter the nucleus to activate target genes. We show that Rac1 and a GTPase
      activating protein, MgcRacGAP, bind directly to p-STAT5A and are required to
      promote its nuclear translocation. Using permeabilized cells, we find that
      nuclear translocation of purified p-STAT5A is dependent on the addition of GTP
      bound Rac1, MgcRacGAP, importin alpha, and importin beta. p-STAT3 also enters the
      nucleus via this transport machinery, and mutant STATs lacking the MgcRacGAP
      binding site do not enter the nucleus even after phosphorylation. We conclude
      that GTP-bound Rac1 and MgcRacGAP function as a nuclear transport chaperone for
      activated STATs.

PMID- 17178911
TI  - Actin turnover-dependent fast dissociation of capping protein in the dendritic
      nucleation actin network: evidence of frequent filament severing.
AB  - Actin forms the dendritic nucleation network and undergoes rapid polymerization
      depolymerization cycles in lamellipodia. To elucidate the mechanism of actin
      disassembly, we characterized molecular kinetics of the major filament end
      binding proteins Arp2/3 complex and capping protein (CP) using single-molecule
      speckle microscopy. We have determined the dissociation rates of Arp2/3 and CP as
      0.048 and 0.58 s(-1), respectively, in lamellipodia of live XTC fibroblasts. This
      CP dissociation rate is three orders of magnitude faster than in vitro. CP
      dissociates slower from actin stress fibers than from the lamellipodial actin
      network, suggesting that CP dissociation correlates with actin filament dynamics.
      We found that jasplakinolide, an actin depolymerization inhibitor, rapidly
      blocked the fast CP dissociation in cells. Consistently, the coexpression of LIM
      kinase prolonged CP speckle lifetime in lamellipodia. These results suggest that
      cofilin-mediated actin disassembly triggers CP dissociation from actin filaments.
      We predict that filament severing and end-to-end annealing might take place
      fairly frequently in the dendritic nucleation actin arrays.

PMID- 17178912
TI  - Roles of type II myosin and a tropomyosin isoform in retrograde actin flow in
      budding yeast.
AB  - Retrograde flow of cortical actin networks and bundles is essential for cell
      motility and retrograde intracellular movement, and for the formation and
      maintenance of microvilli, stereocilia, and filopodia. Actin cables, which are F
      actin bundles that serve as tracks for anterograde and retrograde cargo movement
      in budding yeast, undergo retrograde flow that is driven, in part, by actin
      polymerization and assembly. We find that the actin cable retrograde flow rate is
      reduced by deletion or delocalization of the type II myosin Myo1p, and by
      deletion or conditional mutation of the Myo1p motor domain. Deletion of the
      tropomyosin isoform Tpm2p, but not the Tpm1p isoform, increases the rate of actin
      cable retrograde flow. Pretreatment of F-actin with Tpm2p, but not Tpm1p,
      inhibits Myo1p binding to F-actin and Myo1p-dependent F-actin gliding. These data
      support novel, opposing roles of Myo1p and Tpm2 in regulating retrograde actin
      flow in budding yeast and an isoform-specific function of Tpm1p in promoting
      actin cable function in myosin-driven anterograde cargo transport.

PMID- 17178913
TI  - The nuclear receptor hepatocyte nuclear factor 4alpha acts as a morphogen to
      induce the formation of microvilli.
AB  - Microvilli are actin-based organelles found on apical plasma membranes that are
      involved in nutrient uptake and signal transduction. Numerous components,
      including ezrin/radixin/moesin (ERM) proteins, have been identified that link
      filamentous actins to transmembrane proteins, but the signals driving microvillus
      biogenesis are not known. In this study, we show that the conditional and/or
      ectopic expression of a nuclear receptor, hepatocyte nuclear factor 4alpha
      (HNF4alpha), triggers microvillus morphogenesis. We also demonstrate that
      HNF4alpha expression induces ERM-binding phosphoprotein 50 (EBP50) expression and
      that attenuation of EBP50 using RNA interference inhibits microvillus
      development. We conclude that HNF4alpha acts as a morphogen to trigger
      microvillus formation.

PMID- 17178915
TI  - SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration.
AB  - VCAM-1 is a cell surface molecule, which has been shown to mediate leukocyte
      adhesion to the endothelium and subsequent transmigration. Although VCAM-1
      regulates adhesion through its interaction with VLA-4, VLA-4 does not play a role
      in VCAM-1-dependent diapedesis, an observation suggesting the presence of a
      second ligand for VCAM-1. We now report a novel interaction between VCAM-1 and
      secreted protein acidic and rich in cysteine (SPARC), which induces actin
      cytoskeletal rearrangement and intercellular gaps, physiological processes known
      to be important for leukocyte transmigration. The binding of leukocyte-derived
      SPARC to VCAM-1 was demonstrated to be necessary for leukocyte transmigration
      through endothelial monolayers (diapedesis) in vitro, and furthermore, SPARC null
      mice have abnormalities in leukocyte recruitment to the inflamed peritoneum in
      vivo. These findings provide new insight into the mechanisms of transendothelial
      leukocyte migration and suggest a potential, targetable interaction for
      therapeutic intervention.

PMID- 17178914
TI  - Neurotrophin 3 induces structural and functional modification of synapses through
      distinct molecular mechanisms.
AB  - The mechanisms by which neurotrophins elicit long-term structural and functional
      changes of synapses are not known. We report the mechanistic separation of
      functional and structural synaptic regulation by neurotrophin 3 (NT-3), using the
      neuromuscular synapse as a model. Inhibition of cAMP response element (CRE)
      binding protein (CREB)-mediated transcription blocks the enhancement of
      transmitter release elicited by NT-3, without affecting the synaptic varicosity
      of the presynaptic terminals. Further analysis indicates that CREB is activated
      through Ca(2+)/calmodulin-dependent kinase IV (CaMKIV) pathway, rather than the
      mitogen-activated protein kinase (MAPK) or cAMP pathway. In contrast, inhibition
      of MAPK prevents the NT-3-induced structural, but not functional, changes.
      Genetic and imaging experiments indicate that the small GTPase Rap1, but not Ras,
      acts upstream of MAPK activation by NT-3. Thus, NT-3 initiates parallel
      structural and functional modifications of synapses through the Rap1-MAPK and
      CaMKIV-CREB pathways, respectively. These findings may have implications in the
      general mechanisms of long-term synaptic modulation by neurotrophins.

PMID- 17178916
TI  - Cardiotrophin-1 defends the liver against ischemia-reperfusion injury and
      mediates the protective effect of ischemic preconditioning.
AB  - Ischemia-reperfusion (I/R) liver injury occurs when blood flow is restored after
      prolonged ischemia. A short interruption of blood flow (ischemic preconditioning
      [IP]) induces tolerance to subsequent prolonged ischemia through ill-defined
      mechanisms. Cardiotrophin (CT)-1, a cytokine of the interleukin-6 family, exerts
      hepatoprotective effects and activates key survival pathways like JAK/STAT3. Here
      we show that administration of CT-1 to rats or mice protects against I/R liver
      injury and that CT-1-deficient mice are exceedingly sensitive to this type of
      damage. IP markedly reduced transaminase levels and abrogated caspase-3 and c-Jun
      NH2-terminal kinase activation after I/R in normal mice but not in CT-1-null
      mice. Moreover, the protective effect afforded by IP was reduced by previous
      administration of neutralizing anti-CT-1 antibody. Prominent STAT3
      phosphorylation in liver tissue was observed after IP plus I/R in normal mice but
      not in CT-1-null mice. Oxidative stress, a process involved in IP-induced
      hepatoprotection, was found to stimulate CT-1 release from isolated hepatocytes.
      Interestingly, brief ischemia followed by short reperfusion caused mild serum
      transaminase elevation and strong STAT3 activation in normal and IL-6-deficient
      mice, but failed to activate STAT3 and provoked marked hypertransaminasemia in CT
      1-null animals. In conclusion, CT-1 is an essential endogenous defense of the
      liver against I/R and is a key mediator of the protective effect induced by IP.

PMID- 17178917
TI  - Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary
      fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder
      characterized by activation of fibroblasts and overproduction of extracellular
      matrix (ECM). Caveolin-1 (cav-1), a principal component of caveolae, has been
      implicated in the regulation of numerous signaling pathways and biological
      processes. We observed marked reduction of cav-1 expression in lung tissues and
      in primary pulmonary fibroblasts from IPF patients compared with controls. We
      also demonstrated that cav-1 markedly ameliorated bleomycin (BLM)-induced
      pulmonary fibrosis, as indicated by histological analysis, hydroxyproline
      content, and immunoblot analysis. Additionally, transforming growth factor beta1
      (TGF-beta1), the well-known profibrotic cytokine, decreased cav-1 expression in
      human pulmonary fibroblasts. cav-1 was able to suppress TGF-beta1-induced ECM
      production in cultured fibroblasts through the regulation of the c-Jun N-terminal
      kinase (JNK) pathway. Interestingly, highly activated JNK was detected in IPF-
      and BLM-instilled lung tissue samples, which was dramatically suppressed by ad
      cav-1 infection. Moreover, JNK1-null fibroblasts showed reduced smad signaling
      cascades, mimicking the effects of cav-1. This study indicates a pivotal role for
      cav-1 in ECM regulation and suggests a novel therapeutic target for patients with
      pulmonary fibrosis.

PMID- 17178918
TI  - Puma cooperates with Bim, the rate-limiting BH3-only protein in cell death during
      lymphocyte development, in apoptosis induction.
AB  - The physiological role of B cell lymphoma 2 (Bcl-2) homology 3-only proteins has
      been investigated in mice lacking the individual genes identifying rate-limiting
      roles for Bim (Bcl-2-interacting mediator of cell death) and Puma (p53-up
      regulated modulator of apoptosis) in apoptosis induction. The loss of Bim
      protects lymphocytes from apoptosis induced by cytokine deprivation and
      deregulated Ca++ flux and interferes with the deletion of autoreactive
      lymphocytes and the shutdown of immune responses. In contrast, Puma is considered
      the key mediator of p53-induced apoptosis. To investigate the hypothesis that Bim
      and Puma have overlapping functions, we generated mice lacking both genes and
      found that bim-/-/puma-/- animals develop multiple postnatal defects that are not
      observed in the single knockout mice. Most strikingly, hyperplasia of lymphatic
      organs is comparable with that observed in mice overexpressing Bcl-2 in all
      hemopoietic cells exceeding the hyperplasia observed in bim-/- mice. Bim and Puma
      also have clearly overlapping functions in p53-dependent and -independent
      apoptosis. Their combined loss promotes spontaneous tumorigenesis, causing the
      malignancies observed in Bcl-2 transgenic mice, but does not exacerbate the
      autoimmunity observed in the absence of Bim.

PMID- 17178919
TI  - Control of gene conversion and somatic hypermutation by immunoglobulin promoter
      and enhancer sequences.
AB  - It is thought that gene conversion (GCV) and somatic hypermutation (SHM) of
      immunoglobulin (Ig) genes occur in two steps: the generation of uracils in DNA by
      activation-induced cytidine deaminase, followed by their subsequent repair by
      various DNA repair pathways to generate sequence-diversified products. It is not
      known how either of the two steps is targeted specifically to Ig loci. Because of
      the tight link between transcription and SHM, we have investigated the role of
      endogenous Ig light chain (IgL) transcriptional control elements in GCV/SHM in
      the chicken B cell line DT40. Promoter substitution experiments led to
      identification of a strong RNA polymerase II promoter incapable of supporting
      efficient GCV/SHM. This surprising finding indicates that high levels of
      transcription are not sufficient for robust GCV/SHM in Ig loci. Deletion of the
      IgL enhancer in a context in which high-level transcription was not compromised
      showed that the enhancer is not necessary for GCV/SHM. Our results indicate that
      cis-acting elements are important for Ig gene diversification, and we propose
      that targeting specificity is achieved through the combined action of several Ig
      locus elements that include the promoter.

PMID- 17178922
TI  - Adverse events associated with pediatric spinal manipulation: a systematic
      review.
AB  - BACKGROUND: Spinal manipulation is a noninvasive manual procedure applied to
      specific body tissues with therapeutic intent. Although spinal manipulation is
      commonly used in children, there is limited understanding of the pediatric risk
      estimates. OBJECTIVE: Our goal was to systematically identify and synthesize
      available data on adverse events associated with pediatric spinal manipulation.
      METHODS: A comprehensive search was performed of 8 major electronic databases
      (eg, Medline, AMED, MANTIS) from inception to June 2004 irrespective of language.
      Reports were included if they (1) were a primary investigation of spinal
      manipulation (eg, observation studies, controlled trials, surveys), (2) included
      a study population of children who were aged 18 years or younger, and (3)
      reported data on adverse events. Data were summarized to demonstrate the nature
      and severity of adverse events that may result rather than their incidence.
      RESULTS: Thirteen studies (2 randomized trials, 11 observational reports) were
      identified for inclusion. We identified 14 cases of direct adverse events
      involving neurologic or musculoskeletal events. Nine cases involved serious
      adverse events (eg, subarachnoidal hemorrhage, paraplegia), 2 involved moderately
      adverse events that required medical attention (eg, severe headache), and 3
      involved minor adverse events (eg, midback soreness). Another 20 cases of
      indirect adverse events involved delayed diagnosis (eg, diabetes, neuroblastoma)
      and/or inappropriate provision of spinal manipulation for serious medical
      conditions (ie, meningitis, rhabdomyosarcoma). CONCLUSIONS: Serious adverse
      events may be associated with pediatric spinal manipulation; neither causation
      nor incidence rates can be inferred from observational data. Conduct of a
      prospective population-based active surveillance study is required to properly
      assess the possibility of rare, yet serious, adverse events as a result of spinal
      manipulation on pediatric patients.

PMID- 17178923
TI  - Mycoplasma pneumoniae, splenic infarct, and transient antiphospholipid
      antibodies: a new association?
AB  - We report 2 children with Mycoplasma pneumoniae pulmonary infection with splenic
      infarcts and transient antiphospholipid antibodies. This association has not been
      reported previously.

PMID- 17178920
TI  - A bacterial carbohydrate links innate and adaptive responses through Toll-like
      receptor 2.
AB  - Commensalism is critical to a healthy Th1/Th2 cell balance. Polysaccharide A
      (PSA), which is produced by the intestinal commensal Bacteroides fragilis,
      activates CD4+ T cells, resulting in a Th1 response correcting the Th2 cell skew
      of germ-free mice. We identify Toll-like receptors as crucial to the convergence
      of innate and adaptive responses stimulated by PSA. Optimization of the Th1
      cytokine interferon-gamma in PSA-stimulated dendritic cell-CD4+ T cell co
      cultures depends on both Toll-like receptor (TLR) 2 and antigen presentation.
      Synergy between the innate and adaptive responses was also shown when TLR2-/-
      mice exhibited impaired intraabdominal abscess formation in response to B.
      fragilis. Commensal bacteria, using molecules like PSA, potentially modulate the
      Th1/Th2 cell balance and the response to infection by coordinating both the
      innate and adaptive pathways.

PMID- 17178925
TI  - ATP6V0C competes with von Hippel-Lindau protein in hypoxia-inducible factor
      1alpha (HIF-1alpha) binding and mediates HIF-1alpha expression by bafilomycin A1.
AB  - HIF-1alpha not only enables cells to survive under hypoxic conditions but also
      promotes cell cycle arrest and apoptosis. Therefore, its expression should be
      controlled at optimal levels in growing tumors. We recently reported that
      bafilomycin A1 exorbitantly expressed HIF-1alpha and induced the p21(WAF1/Cip1)
      mediated growth arrest of tumors (Mol Pharmacol 70:1856-1865, 2006). In the
      present study, we addressed the mechanism underlying bafilomycin-induced HIF
      1alpha expression. Bafilomycin stabilized HIF-1alpha under normoxic conditions
      without changes in intracellular pH. However, when ATP6V0C, the target protein of
      bafilomycin, was knocked down, this bafilomycin effect was significantly
      attenuated. Inversely, ATP6V0C expression increased HIF-1alpha levels in a gene
      dose-dependent manner. ATP6V0C competed with Von Hippel-Lindau protein in HIF
      1alpha binding by directly interacting with HIF-1alpha, which was stimulated by
      bafilomycin. In confocal images, ATP6V0C was normally present in the cytoplasm
      but was translocated in company with HIF-1alpha to the nucleus by bafilomycin.
      The N-terminal end (amino acids 1-16) of HIF-1alpha was identified as the ATP6V0C
      interacting motif. These results suggest that ATP6V0C, a novel regulator of HIF
      1alpha, mediates HIF-1alpha expression by bafilomycin.

PMID- 17178921
TI  - IL-21-induced Bepsilon cell apoptosis mediated by natural killer T cells
      suppresses IgE responses.
AB  - Epidemiological studies have suggested that the recent increase in the incidence
      and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely
      correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination;
      however, the underlying mechanisms remain uncertain. Here, we demonstrate that
      natural killer T (NKT) cells in mice and humans play a crucial role in the BCG
      induced suppression of IgE responses. BCG-activated murine Valpha14 NKT cells,
      but not conventional CD4 T cells, selectively express high levels of interleukin
      (IL)-21, which preferentially induces apoptosis in Bepsilon cells. Signaling from
      the IL-21 receptor increases the formation of a complex between Bcl-2 and the
      proapoptotic molecule Bcl-2-modifying factor, resulting in Bepsilon cell
      apoptosis. Similarly, BCG vaccination induces IL-21 expression by human
      peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent
      fashion. BCG-activated PBMCs significantly reduce IgE production by human B
      cells. These findings provide new insight into the therapeutic effect of BCG in
      allergic diseases.

PMID- 17178924
TI  - Role of nuclear factor-kappaB and protein kinase C signaling in the expression of
      the kinin B1 receptor in human vascular smooth muscle cells.
AB  - Kinin B1 receptor expression was characterized in human umbilical artery smooth
      muscle cells to further elucidate the function and specificity of three
      previously proposed pathways [nuclear factor-kappaB (NF-kappaB), protein kinase
      C, and agonist autoregulation] that regulate this inducible G protein-coupled
      receptor. Radioligand binding assays, real-time reverser transcription/polymerase
      chain reaction with an optional actinomycin D treatment period, and NF-kappaB
      immunofluorescence were primarily employed in these primary cell cultures.
      Various stimulatory compounds that increase receptor mRNA stability only (human
      and bovine sera, cycloheximide) or that stimulate NF-kappaB nuclear translocation
      and both mRNA concentration and stability [interleukin (IL)-1beta, phorbol 12
      myristate 13-acetate (PMA)] all increased the density of binding sites for the
      tritiated B1 receptor agonist [3H]Lys-des-Arg9-bradykinin (without change in
      receptor affinity) in cell-based assays. Small interfering RNA assays indicated
      that NF-kappaB p65 is necessary for the effective expression of the cell surface
      B1 receptor under basal or IL-1beta, fetal bovine serum (FBS), or PMA stimulation
      conditions. Dexamethasone cotreatment reproduced these effects. IL-1beta-, FBS-,
      or PMA-induced stabilization of B1 receptor mRNA was inhibited by the addition of
      the protein kinase C inhibitor 3-[1-[3-(dimethylamino)propyl]-1H-indol-3-yl]-4
      (1H-indol-3-yl)-1H-pyrrole-2,5-dione monohydrochloride (GF-109203x), which also
      diminished the Bmax under FBS or PMA treatment. Lys-des-Arg9-bradykinin had
      little effect on NF-kappaB activation, the Bmax, or receptor mRNA abundance or
      stability. Both NF-kappaB and protein kinase C signaling are required for the
      effective expression of the kinin B1 receptor in human umbilical artery smooth
      muscle cells.

PMID- 17178926
TI  - Culture and teasing: the relational benefits of reduced desire for positive self
      differentiation.
AB  - The authors hypothesized that teasing, a social interaction that benefits
      relational bonds at the expense of the self, should be viewed as more
      affiliative, and experienced as more pleasurable, by members of cultures that
      deemphasize positive self-differentiation. In four multimethod studies, Asian
      Americans attributed more affiliative intent to teasers and reported more
      positive target experience than did European Americans. Teaser behavior,
      attribution biases, and personality did not account for culture-related
      differences in teasing experience. Rather, childhood teasing may better prepare
      Asian American children to overlook a tease's affront to the self in favor of its
      relational rewards. Implications of deemphasizing positive self-differentiation
      in social interaction are discussed.

PMID- 17178928
TI  - Why do people perceive ingroup homogeneity on ingroup traits and outgroup
      homogeneity on outgroup traits?
AB  - People tend to perceive ingroup homogeneity on ingroup stereotypical traits and
      outgroup homogeneity on outgroup stereotypical traits (e.g., Kelly, 1989; Simon,
      1992a; Simon & Pettigrew, 1990). If it is assumed that people use homogeneity
      ratings to indicate the extent to which groups possess traits, then this
      stereotype effect may be interpreted as an expression of perceived trait
      possession (i.e., ingroups possess ingroup stereotypical traits and outgroups
      possess outgroup stereotypical traits). If it is further assumed that research
      participants abide by the conversational norm of appropriate quantity (e.g.,
      Bless, Strack, & Schwarz, 1993), then this stereotype effect should be
      significantly reduced following prior expressions of perceived trait possession.
      A literature review and two minimal group experiments (Ns = 75, 104) supported
      this prediction. This evidence is discussed in relation to the outgroup
      homogeneity effect and self-categorization theory.

PMID- 17178927
TI  - Learning what feelings to desire: socialization of ideal affect through
      children's storybooks.
AB  - Previous findings suggest that cultural factors influence ideal affect (i.e., the
      affective states that people ideally want to feel). Three studies tested the
      hypothesis that cultural differences in ideal affect emerge early in life and are
      acquired through exposure to storybooks. In Study 1, the authors established that
      consistent with previous findings, European American preschoolers preferred
      excited (vs. calm) states more (indexed by activity and smile preferences) and
      perceived excited (vs. calm) states as happier than Taiwanese Chinese
      preschoolers. In Study 2, it was observed that similar differences were reflected
      in the pictures (activities, expressions, and smiles) of best-selling storybooks
      in the United States and Taiwan. Study 3 found that across cultures, exposure to
      exciting (vs. calm) storybooks altered children's preferences for excited (vs.
      calm) activities and their perceptions of happiness. These findings suggest that
      cultural differences in ideal affect may be due partly to differential exposure
      to calm and exciting storybooks.

PMID- 17178929
TI  - Systematic and heuristic processing of majority and minority-endorsed messages:
      the effects of varying outcome relevance and levels of orientation on attitude
      and message processing.
AB  - Two experiments investigated the conditions under which majority and minority
      sources instigate systematic processing of their messages. Both experiments
      crossed source status (majority vs. minority) with message quality (strong vs.
      weak arguments). In each experiment, message elaboration was manipulated by
      varying either motivational (outcome relevance, Experiment 1) or cognitive
      (orientating tasks, Experiment 2) factors. The results showed that when either
      motivational or cognitive factors encouraged low message elaboration, there was
      heuristic acceptance of the majority position without detailed message
      processing. When the level of message elaboration was intermediate, there was
      message processing only for the minority source. Finally, when message
      elaboration was high, there was message processing for both source conditions.
      These results show that majority and minority influence is sensitive to
      motivational and cognitive factors that constrain or enhance message elaboration
      and that both sources can lead to systematic processing under specific
      circumstances.

PMID- 17178930
TI  - Humanizing the self: moderators of the attribution of lesser humanness to others.
AB  - Three studies investigated moderators of the tendency to attribute greater
      humanness to the self than to others, an interpersonal counterpart of outgroup
      infra-humanization. Study 1 demonstrated that this self-humanizing effect is
      reduced when the other is the focus of comparison. Study 2 showed that the effect
      is reduced when the other is individuated. Study 3 indicated that empathy does
      not moderate self-humanizing: Self-humanizing failed to correlate negatively with
      dispositional empathy or perspective-taking. Study 3 also indicated that abstract
      construal moderates the self-humanizing effect using a temporal comparison.
      Participants rated their future self, but not their past self, as less human than
      their present self. Studies 1 and 3 also showed that self-humanizing is greater
      for undesirable traits: People may view their failings as "only human." All
      findings were distinct from those attributable to self-enhancement. Self
      humanizing may reflect a combination of egocentrism, focalism, abstract
      representation of others, and motivated processes.

PMID- 17178931
TI  - Stress on the dance floor: the cortisol stress response to social-evaluative
      threat in competitive ballroom dancers.
AB  - The social self-preservation theory states that humans have a fundamental
      motivation to preserve the social self and that threats to the social self
      perturb biological markers such as cortisol. Five studies were designed to
      examine the cortisol response to competitive ballroom dancing as a paradigm for
      real-life social-evaluative threat. Competitive dancing produced substantial
      increases in cortisol compared to a control day. These increases were not due to
      the physical strain of dancing and were greater than those found during social
      evaluative laboratory stressors. Responses did not habituate across competitions
      and were mostly elevated under highly focused conditions of threat (couple vs.
      group competition). These findings support the notion of a social self
      preservation system that is physiologically responsive to threats to the social
      self.

PMID- 17178932
TI  - On emotionally intelligent time travel: individual differences in affective
      forecasting ability.
AB  - In two studies, the authors examined whether people who are high in emotional
      intelligence (EI) make more accurate forecasts about their own affective
      responses to future events. All participants completed a performance measure of
      EI (the Mayer-Salovey-Caruso Emotional Intelligence Test) as well as a self
      report measure of EI. Affective forecasting ability was assessed using a
      longitudinal design in which participants were asked to predict how they would
      feel and report their actual feelings following three events in three different
      domains: politics and academics (Study 1) and sports (Study 2). Across these
      events, individual differences in forecasting ability were predicted by
      participants' scores on the performance measure, but not the self-report measure,
      of EI; high-EI individuals exhibited greater affective forecasting accuracy.
      Emotion Management, a subcomponent of EI, emerged as the strongest predictor of
      forecasting ability.

PMID- 17178933
TI  - Self-efficacy, values, and complementarity in dyadic interactions: integrating
      interpersonal and social-cognitive theory.
AB  - Dyadic interactions were analyzed using constructs from social-cognitive theory
      (self-efficacy and subjective values) and interpersonal theory (interpersonal
      circumplex [IPC] and complementarity). In Study 1, the authors developed a
      measure of efficacy for interpersonal actions associated with each IPC region-
      the Circumplex Scales of Interpersonal Efficacy (CSIE). In Study 2, the authors
      used the CSIE and the Circumplex Scales of Interpersonal Values (which assesses
      the subjective value of interpersonal events associated with each IPC region) to
      predict the dominance expressed and satisfaction experienced by members of 101
      same-sex dyads trying to solve a murder mystery. Structural equation modeling
      analyses supported both social-cognitive and interpersonal theory. A social
      cognitive person-variable (dominance efficacy) and an interpersonal dyadic
      variable (reciprocity) together predicted dominant behaviors. Likewise, both a
      social-cognitive variable (friendliness values) and an interpersonal variable
      (correspondence of friendliness efficacy) predicted satisfaction. Finally, both
      shared performance outcomes and dynamic interpersonal processes predicted
      convergence of collective efficacy beliefs within dyads.

PMID- 17178934
TI  - Mother's milk: an existential perspective on negative reactions to breast
      feeding.
AB  - Drawing from an existential perspective rooted in terror management theory, four
      studies examined the hypothesis that breast-feeding women serve as reminders of
      the physical, animal nature of humanity and that such recognition is threatening
      in the face of one's unalterable mortality. Study 1 demonstrated that mortality
      salience (MS) led to more negative reactions toward a scenario depicting a woman
      breast-feeding her infant in public, and in Study 2, MS decreased liking and
      increased physical avoidance of a potential task partner described as breast
      feeding in another room. Further supporting the hypothesis that such reactions
      are rooted in threats associated with human creatureliness, MS in conjunction
      with a breast-feeding prime led to an increase in the accessibility of creaturely
      related cognitions (Study 3) and priming human/animal similarities (i.e.,
      creatureliness) led to increased negativity toward a magazine cover depicting a
      woman breast-feeding her child (Study 4). Implications of this research are
      discussed.

PMID- 17178935
TI  - Predicting preferences for dating partners from past experiences of psychological
      abuse: identifying the psychological ingredients of situations.
AB  - Are women who have been the victim of psychological abuse in the past more likely
      to prefer an abusive dating partner in the future? Are men who have been the
      perpetrator of abuse more likely to prefer a dating partner with high attachment
      anxiety, a characteristic associated with victims of abuse? The present research
      used a highly repeated, within-subject, multilevel approach to identify the
      characteristics of potential dating partners that constitute salient
      psychological ingredients of situations influencing partner preference. Study 1
      found that college-age women who reported more instances of receiving
      psychological abuse, compared to women who did not, showed a stronger preference
      for male dating partners who possessed characteristics associated with an abusive
      personality (e.g., possessiveness). Study 2 found that college-age men who
      reported more instances of inflicting psychological abuse, compared to men who
      did not, showed a stronger preference for female dating partners characterized by
      high attachment anxiety.

PMID- 17178936
TI  - Phosphatidylinositol 3'-kinase is a critical mediator of interferon-gamma-induced
      increases in enteric epithelial permeability.
AB  - The epithelial lining of mucosal surfaces acts as a barrier to regulate the entry
      of antigen and pathogens. Nowhere is this function of the contiguous epithelium
      more important than in the gut, which is continually exposed to a huge antigenic
      load and, in the colon, an immense commensal microbiota. We assessed the
      intracellular signaling events that underlie interferon (IFN) gamma-induced
      increases in epithelial permeability using monolayers of the human colonic T84
      epithelial cell line. Confluent epithelial monolayers on semipermeable supports
      were treated with IFNgamma (20 ng/ml), and barrier function was assessed 48 h
      later by measuring transepithelial electrical resistance (TER: reflects passive
      ion flux), fluxes of (51)Cr-EDTA and horseradish peroxidase (HRP), and
      transcytosis of noninvasive, nonpathogenic Escherichia coli (strain HB101).
      Exposure to IFNgamma decreased barrier function as assessed by all four markers.
      The phosphatidylinositol 3'-kinase (PI-3K) inhibitors, LY294002 [2-(4
      morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride] and wortmannin, did
      not affect baseline permeability characteristics but completely blocked the drop
      in TER, increased fluxes of (51)Cr-EDTA and HRP, and significantly reduced E.
      coli transcytosis evoked by IFNgamma. In addition, use of the pan-protein kinase
      C (PKC) inhibitor, bisindolylmaleimide I (5 muM), but not rottlerin (blocks
      PKCdelta), partially ameliorated the drop in TER and inhibited increased E. coli
      transcytosis. Addition of the PI-3K and PKC inhibitors to epithelia 6 h after
      IFNgamma exposure still prevented the increase in paracellular permeability but
      not E. coli transcytosis. Thus, IFNgamma-induced increases in epithelial
      paracellular and transcellular permeability are critically dependent on PI-3K
      activity, which may represent an epithelial-specific target to treat immune
      mediated loss of barrier function.

PMID- 17178938
TI  - Ofloxacin otic drops vs neomycin-polymyxin B otic drops as prophylaxis against
      early postoperative tympanostomy tube otorrhea.
AB  - OBJECTIVES: To evaluate the incidence of tympanostomy tube (TT) sequelae, tube
      otorrhea, and tube obstruction immediately postoperatively in patients receiving
      TT for otitis media and to compare patients receiving postoperative otic drops
      with controls. DESIGN: Blinded randomized control trial. SETTING: A tertiary
      pediatric otolaryngology practice. SUBJECTS: The study population comprised 306
      patients undergoing TT placement. INTERVENTIONS: The 306 patients were enrolled
      into the following 3 groups: (1) those receiving no postoperative otic drop
      prophylaxis (control group), (2) those receiving ofloxacin otic drops (FLOX
      group), and (3) those receiving neomycin sulfate-polymyxin B sulfate
      hydrocortisone otic drops (COS group). RESULTS: Overall otorrhea rates
      postoperatively were 14.9% for the control group, 8.1% for the FLOX group, and
      5.5% for the COS group. When controlling for disease severity, the rate of
      otorrhea was significantly higher for the control group than for both the FLOX (P
      = .04) and COS (P = .01) groups. Nonpatent, plugged, tube rates were added to
      otorrhea rates for a TT failure analysis postoperatively. The control group
      demonstrated a significantly greater failure rate (29.9%) than both the FLOX
      (12.1%) and COS (7.7%) groups. The only differences between the patients in the 2
      groups receiving drops were that ofloxacin was more well liked by patients (P =
      .04) and caused less pain (P = .004). CONCLUSIONS: Nonpatency and otorrhea are
      the most frequent sequelae immediately following TT placement. Few studies have
      compared different treatment regimens in a randomized controlled trial. These
      results demonstrate that otic drops clearly provide benefit postoperatively in
      preventing TT plugging and otorrhea but primarily in patients who have middle ear
      fluid at the time of TT placement. In addition, consideration of drop choice
      should be based on patient tolerance and medication safety profiles.

PMID- 17178939
TI  - Radiographic classification of temporal bone fractures: clinical predictability
      using a new system.
AB  - OBJECTIVE: To compare the traditional system of radiographic classification of
      temporal bone fractures (transverse vs longitudinal vs oblique) with a newer
      system (otic capsule violating vs otic capsule sparing) with respect to their
      ability to predict sequelae of temporal bone trauma. DESIGN: Retrospective chart
      and radiology review. SETTING: University trauma center and Department of
      Otolaryngology-Head and Neck Surgery. PATIENTS: Patients with temporal bone
      fractures. INTERVENTIONS: Clinic records and computed tomographic scans were
      reviewed to evaluate the clinical predictability of complications of temporal
      bone fractures. MAIN OUTCOME MEASURES: Complications of temporal bone fractures
      (ie, sensorineural hearing loss, conductive hearing loss, cerebrospinal fluid
      leakage, and facial nerve weakness) were recorded. Two classification schemes for
      temporal bone fractures were statistically analyzed and compared as to their
      ability to predict each complication. RESULTS: A total of 234 temporal bone
      fractures were identified; 30 cases met our strict criteria for inclusion. The
      traditional classification system of temporal bone fractures did not
      significantly predict temporal bone complications (P = .71). On the other hand,
      the otic capsule-based system did demonstrate statistically significant
      predictive ability (P < .001). Patients with otic capsule-violating fractures
      were 5 times more likely to have facial nerve injury, 25 times more likely to
      have sensorineural hearing loss, and 8 times more likely to have cerebrospinal
      fluid otorrhea than those with otic capsule-sparing fractures. CONCLUSIONS: The
      traditional radiographic classification system failed to demonstrate clinical
      predictability in our series. Furthermore, the newer system of classification
      (otic capsule sparing vs otic capsule violating) demonstrated statistically
      significant predictive ability for serious clinical outcomes associated with
      temporal bone fractures.

PMID- 17178940
TI  - Analysis of mastoid findings at surgery to treat middle ear cholesteatoma.
AB  - OBJECTIVES: To analyze mastoid findings, such as facial nerve dehiscence (FND),
      labyrinthine fistula, and dural exposure; to review its incidence at
      cholesteatoma surgery; to analyze its association with semicircular canal
      fistula; and to elucidate its relationship with dural exposure. DESIGN: One
      hundred fifty-two patients (65 males and 87 females; 155 ears) were enrolled in a
      retrospective study of tympanoplasty with or without mastoidectomy. SETTING:
      Medical university center hospital. RESULTS: The incidence of FND after
      exenteration of disease was 29.7% (46/155 ears) for total surgical procedures,
      29.7% (43/145 ears) for initial procedures, and 30% (3/10 ears) for revision
      procedures. The prevalence of FND in the tympanic segment only was 87%, with 8.7%
      in the vertical segment only and 4.3% in both segments. Three patients (2.0%)
      developed facial palsy postoperatively, with 8 lateral semicircular canal
      fistulas (5.2% of total ears operated on), half of these with concomitant FND.
      The incidence of dural exposure of the mastoid tegmen in the entire surgical
      group was 16.8% (26 ears), 38.5% with concomitant FND. CONCLUSIONS: The overall
      incidence of FND in our sample was high at 29.7%, with rates of lateral
      semicircular canal fistula and dural exposure of 5.2% and 16.8%, respectively.
      The relationship between FND incidence and presence of lateral semicircular canal
      fistula was positive in our study. The surgeon should bear in mind that the
      location of FND with cholesteatoma coincides with the most common area of
      iatrogenic facial nerve injury during otologic surgery.

PMID- 17178941
TI  - Meniett clinical trial: long-term follow-up.
AB  - OBJECTIVE: To delineate 2-year efficacy of Meniett device therapy in people with
      classic, unilateral, Meniere's disease unresponsive to traditional medical
      treatment. DESIGN: A 2-year long-term unblinded follow-up after a prior
      randomized, placebo-controlled, multicenter clinical trial of the Meniett device
      for Meniere's disease. SETTING: Follow-up was performed remotely by using diaries
      and questionnaires mailed to the data coordinating center by the participants.
      Those who failed to mail their diaries were interviewed by telephone.
      PARTICIPANTS: Sixty-one study participants agreed to use the Meniett device and
      report their symptoms for 2 years. All had active, unilateral cochleovestibular
      disease. Outcomes are available for 58 participants; 2 were unavailable for
      follow-up and 1 was excluded because of a concurrent condition that precluded
      Meniett device use. INTERVENTIONS: Participants were advised to adhere to a low
      sodium diet, use the Meniett device 3 times daily, and maintain a patent
      tympanostomy tube in the affected ear. Diuretic and vestibular suppressant
      medications were used as needed. MAIN OUTCOME MEASURES: Outcomes were based on
      the participants' daily diary, questionnaires, and telephone interviews. Three
      different analyses were prepared: tracking of vertigo frequency throughout the
      study, comparison of vertigo frequency before and at the end of Meniett device
      use (American Academy of Otolaryngology-Head and Neck Surgery Foundation
      reporting guideline), and Kaplan-Meier estimates of vertigo remission and
      recurrence. RESULTS: Vertigo levels gradually improved for most but not all
      participants. American Academy of Otolaryngology-Head and Neck Surgery Foundation
      class A (remission) or class B (greatly improved) results occurred in 67% (39/58)
      of participants, and class F (dropped out to receive surgical therapy) results
      occurred in 24%. Of the 44 nondropout participants, 39 (89%) had American Academy
      of Otolaryngology-Head and Neck Surgery Foundation group A or B outcomes. People
      who went into remission were highly likely (80%) to remain in remission long
      term; participants who achieved remission (20/43; 47%) did so within the first
      year of follow-up. CONCLUSIONS: Use of the Meniett device was associated with a
      significant reduction in vertigo frequency in about two thirds of the
      participants, and this improvement was maintained long term. Therapy with the
      Meniett device is a safe and effective option for people with substantial vertigo
      uncontrolled by medical therapy.

PMID- 17178942
TI  - The Z-meatoplasty for modified radical mastoidectomy in children.
AB  - OBJECTIVE: To determine the effectiveness of the Z-meatoplasty technique for
      enlargement of the external auditory meatus of children undergoing modified
      radical mastoidectomy. DESIGN: Case series. SETTING: Pediatric otolaryngology
      practice in an academic setting. PATIENTS: Consecutive sample of children (< or
      =18 years old) who had undergone modified radical mastoidectomy performed by the
      author from 1995 to 2005. INTERVENTION: Z-meatoplasty technique used as part of
      modified radical mastoidectomy. MAIN OUTCOME MEASURE: Development of
      postoperative stenosis of the external auditory meatus that required additional
      surgery. RESULTS: A total of 28 children and 29 ears were treated with modified
      radical mastoidectomy during the study period. The Z-meatoplasty was used in 24
      ears, and 3 (12.5%) required revision meatoplasty for meatal stenosis. Twenty-one
      ears (87.5%) treated with Z-meatoplasty had excellent healing and cosmesis
      without stenosis, during a mean follow-up period of 40 months. CONCLUSION: The Z
      meatoplasty is an effective technique for use during modified radical
      mastoidectomy to treat children with cholesteatoma.

PMID- 17178943
TI  - Factors influencing tinnitus loudness and annoyance.
AB  - OBJECTIVE: To evaluate the 2 major components of tinnitus severity, loudness and
      annoyance, and their degree of dependence on characteristics of tinnitus
      manifestation, history, and etiology. DESIGN: Cross-sectional survey performed
      during the first months of 2004. SETTING: Nonclinical population. PARTICIPANTS: A
      total of 4995 members of the German Tinnitus League. MAIN OUTCOME MEASURES:
      Comprehensive screening questionnaire, including the Klockhoff and Lindblom
      loudness grading system and the miniversion of the Tinnitus Questionnaire.
      RESULTS: A moderate correlation of 0.45 was found between tinnitus loudness and
      annoyance. Both factors were generally higher in men, those older than 50 years,
      those with binaural and centrally perceived tinnitus, those with increased noise
      sensitivity, and those who had continuous tinnitus without interruptions.
      Tinnitus that lasted 12 months or less had a stronger influence on annoyance
      (odds ratio [OR], 1.96) than on loudness (OR, 0.45), whereas the contrary was
      found for tinnitus of more than 5 years' duration (ORs, 0.72 and 2.11,
      respectively). Loudness and annoyance were increased in subjects with coexisting
      hearing loss, vertigo, and hyperacusis. The impact of hyperacusis on annoyance
      was clearly stronger than on loudness (ORs, 21.91 vs 9.47). CONCLUSIONS: Several
      clinical factors of tinnitus influence perceived loudness and annoyance. Both are
      distinguishable components of tinnitus severity.

PMID- 17178944
TI  - Association between cupular deposits and otosclerosis.
AB  - OBJECTIVE: To evaluate whether otosclerosis is an underlying mechanism for the
      production of cupular deposits and to study the association between cupular
      deposits and dysequilibrium in otosclerosis. DESIGN: Retrospective human temporal
      bone (TB) study. The incidence of cupular deposits in these 70 TBs was analyzed.
      Correlations between cupular deposits and vestibular symptoms, endosteal
      involvement of the otosclerotic focus, stapedial fixation, and clinical history
      of stapes surgery were evaluated. SETTING: Otolaryngology laboratory in a
      tertiary academic medical center. PATIENTS: The study material consisted of 35
      human TBs with otosclerosis and 35 age-matched controls. MAIN OUTCOME MEASURES:
      Morphometric evaluations of the incidence of cupular deposits, endosteal
      involvement of the otosclerotic focus, and stapedial fixation were made by light
      microscopy. Clinical records were reviewed retrospectively for clinical history
      of stapes surgery and prevalence of vestibular symptoms. The incidence of cupular
      deposits was compared between the otosclerotic and control groups. Correlations
      between cupular deposits and vestibular symptoms, endosteal involvement of the
      otosclerotic focus, stapedial fixation, and clinical history of stapes surgery
      were evaluated in the subjects with otosclerosis. RESULTS: The incidence of
      cupular deposits in TBs with otosclerosis was significantly higher than in those
      without whereas there was no correlation between the incidence of the deposits
      and dysequilibrium in cases of otosclerosis. An increase in deposits did not
      correlate with stapedial fixation, stapes surgery, or endosteal involvement.
      CONCLUSIONS: Our results suggest otosclerosis as an underlying mechanism for the
      production of cupular deposits; however, we did not find an association between
      these deposits and vestibular symptoms.

PMID- 17178945
TI  - The presentation and management of laryngeal cleft: a 10-year experience.
AB  - OBJECTIVE: To review the presentation and associated congenital abnormalities of
      laryngeal cleft and present guidelines for its evaluation and management. DESIGN:
      A 10-year retrospective study (1994-2004) with institutional review board
      approval. SETTING: Two pediatric tertiary care medical centers. PATIENTS: Twenty
      two pediatric patients (mean age, 21 months) with laryngeal cleft. INTERVENTION:
      Surgical repair of laryngeal cleft. MAIN OUTCOME MEASURES: Sex, age, symptoms,
      other associated abnormalities, method of evaluation, type of laryngeal cleft,
      method of surgical repair, treatment outcome, complications, and long-term follow
      up. RESULTS: All 22 patients underwent surgical repair for laryngeal cleft.
      Airway endoscopy confirmed the following types of laryngeal clefts: type 1 (n =
      3), type 2 (n = 10), and type 3 (n = 9). Surgical repair techniques included an
      open approach with or without interposition graft (n = 16) and an endoscopic
      approach (n = 6). CONCLUSIONS: Early diagnosis and proper repair of laryngeal
      cleft are essential to prevent pulmonary damage and associated morbidity. Each
      patient should be assessed properly, and the surgical approach should be
      individualized based on the symptoms, other associated findings on airway
      endoscopy, and type of cleft.

PMID- 17178946
TI  - Changes in the cricoarytenoid joint induced by intubation in neonates.
AB  - OBJECTIVE: To characterize the histopathologic characteristics of the
      cricoarytenoid joint (CAJ) as a means to understand the mechanisms of vocal cord
      fixation in children after prolonged intubation. DESIGN: Histologic analysis of
      laryngeal specimens obtained from infants who had died secondary to various
      causes and who had been intubated from 1 to 30 days. MAIN OUTCOME MEASURE:
      Histopathologic characteristics of CAJ. RESULTS: Laryngeal specimens from infants
      who had been intubated for prolonged periods of time demonstrated evidence of
      hemorrhage, infection, inflammation, and fibrosis within the CAJ. Furthermore, a
      statistical correlation was found between the length of intubation and the
      presence of these histologic abnormalities. CONCLUSIONS: To our knowledge, this
      is the first study to demonstrate histologic changes in the CAJ in laryngeal
      specimens of children who have been intubated for prolonged periods of time. Such
      histological changes in the CAJ could explain the mechanism of vocal cord
      immobility in children after intubation.

PMID- 17178948
TI  - Potential role of abnormal ion transport in the pathogenesis of chronic
      sinusitis.
AB  - OBJECTIVES: To create well-differentiated cultures of normal and chronic
      sinusitis paranasal sinus epithelial cells and to compare their
      electrophysiologic properties. DESIGN: In vitro investigation using primary sinus
      epithelial cells, initially cultured on plastic tissue culture dishes. Cells were
      characterized by means of immunocytochemical analysis and then passaged to air
      liquid interface culture conditions. The morphologic features of air-liquid
      interface cultures were assessed using light and electron microscopy. Epithelial
      Na(+) channel, Na(+)-K(+)-2Cl(-) cotransporter, cystic fibrosis transmembrane
      conductance regulator, and Ca(2+)-activated Cl(-) channel function were
      investigated in Ussing chambers. SUBJECTS: Specimens were obtained from 15
      patients undergoing transsphenoidal pituitary procedures, tumor removal, or
      trauma repair and from 9 patients with chronic sinusitis. RESULTS: After culture
      at an air-liquid interface for 21 days, the epithelium was pseudostratified and
      contained basal, mucous secretory, and ciliated cells. There were no detectable
      morphologic differences between normal and chronic sinusitis cells. In cultures
      of normal cells, median basal short circuit current was 4.7 microA/cm(2), and
      Na(+) transport, defined as the amiloride hydrochloride-sensitive component, was
      approximately 20% of the total. Basal and amiloride-sensitive short circuit
      currents were greater in cultures of chronic sinusitis cells. Basal short circuit
      currents in both types of cultures were insensitive to the Cl(-) transport
      inhibitor bumetanide, but all responded to forskolin or uridine triphosphate.
      After amiloride pretreatment, forskolin and uridine triphosphate responses were
      greater in chronic sinusitis cells. CONCLUSIONS: We established methods for well
      differentiated sinus epithelial cultures. The cells exhibited Na(+) absorption
      and Cl(-) secretion, and elevated rates of ion transport may be
      pathophysiologically relevant in chronic sinusitis.

PMID- 17178947
TI  - Olfactory function assessed with orthonasal and retronasal testing, olfactory
      bulb volume, and chemosensory event-related potentials.
AB  - OBJECTIVE: To investigate whether differences in olfactory function between
      healthy individuals and patients with olfactory loss could be detected by various
      diagnostic tests. DESIGN: Psychophysical testing of orthonasal and retronasal
      olfactory functions, magnetic resonance imaging of olfactory bulb (OB) volume,
      and chemosensory event-related potential (ERP) measurement performed between
      January 1, 2005, and October 31, 2005. SETTING: Academic tertiary referral
      medical center. PATIENTS: Eleven healthy individuals with normal olfactory
      function (NL) and 11 patients with nasal polyposis (NP), 11 with posttraumatic
      olfactory loss (PT), and 11 with postinfectious olfactory loss (PI) were included
      in this study. MAIN OUTCOME MEASURES: Orthonasal and retronasal olfactory test
      results, magnetic resonance imaging-based OB volume, and ERPs to both olfactory
      and intranasal trigeminal stimulation. RESULTS: Orthonasal and retronasal testing
      revealed that NL individuals had higher scores than patients with NP, PT, or PI.
      Retronasal scores were higher in NP patients compared with PT and PI patients.
      The OB volumes were higher in NL individuals compared with NP, PT, and PI
      patients. The OB volumes in PT patients were significantly lower than those from
      NP and PI patients. Olfactory ERPs were different between NL individuals and NP,
      PT, and PI patients, and trigeminal ERPs were significantly different when
      comparing NL individuals with NP patients. For the entire cohort, a significant
      correlation was found between orthonasal testing and OB volume, between
      retronasal testing and OB volume, and between both orthonasal and retronasal
      testing and olfactory ERP amplitudes. Olfactory ERPs were recorded in the 11 NL
      individuals and in 3 NP, 3 PT, and 4 PI patients, defined as responders.
      Orthonasal and retronasal test scores, OB volume, and olfactory ERPs were
      significantly larger in responders compared with nonresponders. CONCLUSIONS:
      Significant differences in various tests that evaluate olfactory function were
      detectable in a cohort of NL individuals and NP, PT, and PI patients. This
      finding suggests that these diagnostic tools provide information in terms of the
      clinical assessment of olfactory function. Future studies will investigate their
      combined use in terms of the prognosis of olfactory function in patients with
      olfactory loss.

PMID- 17178950
TI  - Vascular evaluation in laryngeal diseases: comparison between contact endoscopy
      and laser Doppler flowmetry.
AB  - OBJECTIVE: To determine the efficacies of 2 methods for evaluating vascular
      changes in laryngeal diseases. DESIGN: Prospective comparative study. SETTING:
      University hospital. PATIENTS: Twenty-four adults planning to undergo
      laryngomicrosurgery for unilateral lesions in their vocal cords. INTERVENTION:
      Vascular evaluation was performed using contact endoscopy and laser Doppler
      flowmetry during laryngomicrosurgery. MAIN OUTCOME MEASURES: Morphological and
      physiological variables of the vascular changes. RESULTS: Contact endoscopy
      examinations revealed changes in the fine vascular network patterns in the vocal
      cords. Hypervascularity was present in patients with polyps but not in those with
      nodules, and the degree of vascularity was variable in patients with malignant
      neoplasms. Patients with papillomas and patients in the postradiation therapy
      group showed hypovascularity with losses in the capillary network. Laser Doppler
      flowmetry revealed high mean blood flows in patients with polyps, dysplasia, and
      malignant neoplasms, whereas patients with papillomas and those in the
      postradiation therapy group had low blood flows. The variables measured by laser
      Doppler flowmetry and endoscopy were strongly correlated. CONCLUSION: Evaluations
      of morphological and physiological changes of vascularity in laryngeal diseases
      are important for understanding their pathophysiology, and combining contact
      endoscopy and laser Doppler flowmetry is useful in such evaluations.

PMID- 17178949
TI  - In vitro enzymatic treatment and carbon dioxide laser beam irradiation of
      morphologic cartilage specimens.
AB  - OBJECTIVES: To determine the role of the main cartilage components in the
      internal system of interlocked stresses and to clarify the effect of laser beam
      irradiation on cartilage. DESIGN: Control and experimental series. SUBJECTS:
      Rabbit ear cartilage. INTERVENTION: Rabbit ear cartilage strips incubated in
      collagenase and hyaluronidase enzyme solutions for specific periods were
      examined, and the observed changes in shape, strength, and elasticity were
      recorded, as well as the effect of carbon dioxide laser irradiation. Laser
      pretreated cartilage strips were also incubated in the enzyme solutions to
      determine whether the laser-provoked changes were susceptible to enzymatic
      action. All cartilage pieces were examined by light and electron microscopy.
      RESULTS: Collagenase-treated cartilage strips gradually lost their interlocked
      stresses, while hyaluronidase-treated strips mostly maintained their shape and
      their physical characteristics. Hyaluronidase-incubated cartilage strips altered
      their shape when they were laser treated. Collagenase-treated cartilages did not
      modify their shape when they were laser treated. Laser-pretreated cartilage
      pieces lost their new form in collagenase solutions but kept their laser-evoked
      shape when put in hyaluronidase solutions. CONCLUSION: The macroscopic
      observations combined with light and electron microscopy findings argue for the
      distinct role of the collagen network in morphologic cartilage shape and tensile
      strength preservation and provide a probable mechanism of cartilage
      transformation owing to carbon dioxide laser irradiation.

PMID- 17178951
TI  - A cytomegalovirus-associated mass presenting with laryngeal obstruction.

PMID- 17178952
TI  - Foreign body reaction to calcium hydroxylapatite vocal fold augmentation.

PMID- 17178953
TI  - Radiology quiz case 1. Schwannoma of the tongue.

PMID- 17178954
TI  - Radiology quiz case 2. Giant cell tumor (GCT) of the temporal bone.

PMID- 17178955
TI  - Pathology quiz case 1. Osteoma of the larynx.

PMID- 17178956
TI  - Pathology quiz case 2. Parathyroid lipoadenoma.

PMID- 17178957
TI  - The value of chemoprophylaxis against Enterococcus species in elective
      cholecystectomy: a randomized study of cefuroxime vs ampicillin-sulbactam.
AB  - HYPOTHESIS: Cephalosporins are widely used and considered to be effective as
      prophylaxis in biliary surgery. Nevertheless, they lack activity against
      enterococci. We conducted a study to compare the efficacy of ampicillin-sulbactam
      vs cefuroxime in preventing surgical site infections following elective
      cholecystectomy. DESIGN: A prospective randomized controlled trial. SETTING: A
      major tertiary care hospital. PATIENTS: Four hundred eighteen randomized patients
      (of 549 total), who from July 2002 to August 2004 underwent elective open or
      laparoscopic cholecystectomy with prospective assessment for development of
      surgical site infections for 1 month postoperatively. INTERVENTION: A single
      intravenous dose of 1.5 g of cefuroxime (group A, n = 207) or 3 g of ampicillin
      sulbactam (group B, n = 211) was administered during induction of anesthesia.
      Bile and gallbladder mucosal cultures were taken intraoperatively from all
      patients. MAIN OUTCOME MEASURE: Number of postoperative surgical site infections.
      RESULTS: A postoperative surgical site infection was noted in 19 (4.5%) of 418
      patients, 18 from group A and 1 from group B (P<.001). In the group that received
      cefuroxime, 15 (83.3%) of 18 surgical site infections were due to Enterococcus
      species. Intraoperative bactibilia as well as intraoperative gallbladder rupture
      were associated with surgical site infections (P<.001). CONCLUSIONS: A single
      dose of ampicillin-sulbactam favored better compared with cefuroxime for
      prevention of postoperative surgical site infections due to Enterococcus species
      after elective cholecystectomy. Ampicillin-sulbactam may be a better agent for
      antimicrobial prophylaxis in high-risk patients undergoing elective
      cholecystectomy, especially in a setting where the incidence of enterococcal
      infections is higher.

PMID- 17178958
TI  - Povidone-iodine vs sodium hypochlorite enema for mechanical preparation before
      elective open colonic or rectal resection with primary anastomosis: a multicenter
      randomized controlled trial.
AB  - HYPOTHESIS: The anti-infective actions of povidone-iodine (PVI) and sodium
      hypochlorite enemas are different. DESIGN: Prospective, randomized, single-blind
      study. SETTING: Multicenter. PATIENTS: Five hundred seventeen consecutive
      patients with colorectal carcinoma or sigmoid diverticular disease undergoing
      elective open colorectal resection, followed by primary anastomosis.
      INTERVENTION: All patients received senna (1-2 packages diluted in a glass of
      water) at 6 pm the evening before surgery. Patients were administered two 2-L
      aqueous enemas of 5% PVI (n = 277) or 0.3% sodium hypochlorite (n = 240) at 9 pm
      the evening before surgery and at 3 hours before operation. Intravenous
      ceftriaxone sodium (1 g) and metronidazole (1 g) were administered at anesthetic
      induction. MAIN OUTCOME MEASURE: Rate of patients with 1 infective
      parietoabdominal complication or more. RESULTS: The percentages of patients with
      1 infective parietoabdominal complication or more did not differ between the 2
      groups (13.7% in the PVI-treated group vs 15.0% in the sodium hypochlorite
      treated group). Tolerance was better in the PVI-treated group than in the sodium
      hypochlorite-treated group (79.4% vs 67.9%), with fewer patients experiencing
      abdominal pain (13.0% vs 24.6%) or discontinuing their preparation (3.0% vs 9.0%)
      (P=.02 for all). There were more patients with malaise in the PVI-treated group
      than in the sodium hypochlorite-treated group (9.1% vs 4.9%, P<.05). Three
      patients in the sodium hypochlorite-treated group had necrotic ulcerative
      colitis. CONCLUSION: When antiseptic enemas are chosen for mechanical preparation
      before colorectal surgery, PVI should be preferred over sodium hypochlorite
      because of better tolerance and avoidance of necrotic ulcerative colitis.

PMID- 17178959
TI  - Web relationships between physicians and individuals seeking information on
      hepatopancreatobiliary diseases.
AB  - HYPOTHESIS: The Internet has led to widespread Web consulting, the proportions of
      which are not yet known; there is not yet agreement on its management. DESIGN: We
      verified the typology and needs of people and patients of a single-language
      population inquiring about a homogeneous group of diseases treated in tertiary
      reference centers and their reason for writing. Data were extracted and coded
      from e-mail messages received over 27 months by a noninstitutional Web site
      devoted to surgically treatable hepatopancreatobiliary diseases. Consultation
      activity was verified by the number of answers and subsequent messages. MAIN
      OUTCOME MEASURES: One thousand forty-seven users sent 1788 messages to one of the
      Web site addresses; 1179 (94.6%) of them inquired about clinical problems. Data
      were collected on the demographics of senders and patients, the nature of the
      clinical problem, and the reasons for the messages. RESULTS: A mean of 2.1
      messages per day were received. Queries were sent by patients in 260 instances
      (22.1%) and by others in 750 (63.6%). Two hundred thirty-seven (20.1%) e-mails
      had medical enclosures. The presence of a malignant disease was reported in 705
      messages (59.8%). Description of previously undertaken therapy was present in 613
      cases (52.0%). An answer was given to 1177 first messages (94.4%) and a follow-up
      message was received from 401 users (34.1%). Second messages were characterized
      by a shorter time to receive an answer (mean, 2.5 +/- 3.6 days vs 3.5 +/- 5.3
      days). Each user sent a mean number of 1.4 +/- 0.7 messages (range, 1-8).
      CONCLUSIONS: Web consulting is a powerful tool for patients and health
      professionals that emerged owing to physician communication problems.
      Nevertheless, the Internet is still pushing physicians toward a reconsideration
      of the principles of medical ethics and a reevaluation of rules and regulations
      to deal with these new communication methods.

PMID- 17178961
TI  - Mucosal wound healing: the roles of age and sex.
AB  - HYPOTHESIS: It remains unclear whether aging delays wound healing, as past human
      studies have not adequately controlled for confounding factors such as morbidity
      and medications. Furthermore, although dermal wounds heal more quickly in women
      than in men, clinical observations suggest that the opposite may be true for
      mucosal healing. We assessed age and sex differences in mucosal wound healing,
      and we hypothesized that aging delays healing and sex modulates healing
      independent of age. DESIGN AND SETTING: Clinical experimental study performed
      from June 2000 to August 2003 involving younger and older adult volunteers from
      the general community. PARTICIPANTS: Two hundred twelve male and female
      volunteers aged 18 to 35 years (n = 119) or 50 to 88 years (n = 93).
      INTERVENTION: Standardized 3.5-mm circular wounds were placed on the oral hard
      palates of volunteers. MAIN OUTCOME MEASURE: Wound videographs were taken daily
      for 7 days after wounding to assess wound closure. RESULTS: Wounds healed
      significantly more slowly in older adults compared with younger adults (P<.001)
      regardless of sex. This remained true even when individuals receiving medication
      and/or having a coexisting medical condition were excluded. Mucosal wounds healed
      more slowly in women than in men (P = .008) regardless of age. These effects were
      independent of demographic factors such as ethnicity, alcohol or nicotine use, or
      body mass index. CONCLUSIONS: Wound closure in older individuals was clearly
      delayed even when eliminating potential age-related confounds, indicating that
      aging does slow wound healing. Wound closure in women was also delayed,
      suggesting that wound healing is modulated by different mechanisms depending on
      tissue type. These findings may help target patients with increased surgical
      risks and greater need for postsurgical care.

PMID- 17178960
TI  - Association between alcohol and mortality in patients with severe traumatic head
      injury.
AB  - HYPOTHESIS: Admission blood alcohol concentration (BAC) is associated with in
      hospital death in patients with severe brain injury from blunt head trauma.
      DESIGN: Retrospective cohort study. SETTING: Academic level I trauma center in
      Toronto, Ontario. PATIENTS: Using trauma registry data, between January 1, 1988,
      and December 31, 2003, we identified 1158 consecutive patients with severe brain
      injury from blunt head trauma. INTERVENTION: There was no active intervention.
      The primary exposure of interest was the BAC at admission, stratified into the
      following 3 levels: 0, no BAC; 0 to less than 230 mg/dL, low to moderate BAC; and
      230 mg/dL or greater, high BAC. MAIN OUTCOME MEASURE: In-hospital death. RESULTS:
      In patients with severe brain injury, low to moderate BAC was associated with
      lower mortality than was no BAC (27.9% vs 36.3%; P = .008). High BAC was
      associated with higher mortality than was no BAC (44.7% vs 36.3%), although this
      was not statistically significant (P = .10). These associations were all
      statistically significant after adjusting for demographic data and injury factors
      using logistic regression analysis. The odds ratio for death was 0.76 (95%
      confidence interval, 0.52-0.98) for low to moderate BAC compared with no BAC. The
      odds ratio for death was 1.73 (95% confidence interval, 1.05-2.84) for high BAC
      compared with no BAC. CONCLUSIONS: Low to moderate BAC may be beneficial in
      patients with severe brain injury from blunt head trauma. In contrast, high BAC
      seems to have a deleterious effect on in-hospital death in these patients, which
      may be related to its detrimental hemodynamic and physiologic effects. Alcohol
      based fluids may have a role in the management of patients with severe brain
      injury after they have been well resuscitated.

PMID- 17178962
TI  - Estimated risk of pheochromocytoma recurrence after adrenal-sparing surgery in
      patients with multiple endocrine neoplasia type 2A.
AB  - HYPOTHESIS: Adrenal-sparing adrenalectomy is considered the treatment of choice
      for hereditary bilateral pheochromocytoma in patients with multiple endocrine
      neoplasia type 2A (MEN 2A). DESIGN: Retrospective analysis of prospectively
      documented data with a mean +/- SD follow-up of 81.5 +/- 85.3 months. The PubMed
      database was searched for articles published between 1975 and 2004 to identify
      published series and/or case reports. SETTING: University hospital referral
      center. PATIENTS: In 17 (22%) of 77 patients with various mutations of the RET
      proto-oncogene, unilateral (n = 12) or bilateral (n = 5) pheochromocytomas were
      documented at the time of diagnosis or during the course of MEN 2A. Adrenal
      sparing surgery was performed in 13 patients (group 1), synchronous bilateral
      total adrenalectomy in 4 patients (group 2A), and metachronous bilateral total
      adrenalectomy in 5 patients after adrenal-sparing adrenalectomy (group 2B). MAIN
      OUTCOME MEASURES: Measurement of 24-hour urinary catecholamine levels
      (noradrenaline, adrenaline, and dopamine) and, in case of high catecholamine
      levels, imaging studies to localize the tumors in 1 or both adrenal glands to
      determine the size and exclude extra-adrenal tumors and distant metastasis.
      RESULTS: The mean+/-SD estimated 5- and 10-year cumulative risk of developing
      recurrence in both groups was 38.5% +/- 15.7%. Five (38%) of 13 patients in group
      1 developed recurrence in the contralateral gland. Two (22%) of 9 patients in
      groups 2A and 2B developed several episodes of an addisonian crisis, 1 of whom
      died. CONCLUSIONS: Substantial morbidity and mortality are associated with
      addisonian crisis after bilateral adrenalectomy. Adrenal-sparing adrenalectomy
      and close monitoring of the remnant may be the treatment of choice for hereditary
      bilateral pheochromocytoma in MEN 2A, since overall recurrence is low.

PMID- 17178963
TI  - Iatrogenic bile duct injury: a population-based study of 152 776
      cholecystectomies in the Swedish Inpatient Registry.
AB  - HYPOTHESIS: Older age, male sex, and low yearly hospital volume of
      cholecystectomy may increase the risk of bile duct injury (BDI), whereas the use
      of intraoperative cholangiography may decrease the risk. The incidence of BDI at
      cholecystectomy may have increased after the introduction of laparoscopic
      cholecystectomy. DESIGN: Nationwide population-based study of all
      cholecystectomies registered in the Swedish Inpatient Registry from 1987 through
      2001. SETTING: All hospitals performing inpatient cholecystectomies in Sweden.
      PATIENTS: Cholecystectomies were identified using International Classification of
      Diseases, Ninth and 10th Revisions surgical procedure codes. After exclusion of
      patients with hepatobiliary and pancreatic malignancies, patients with codes
      indicating reconstructive bile duct operations within 1 year after
      cholecystectomy were considered BDI cases. Risk factors for BDI were analyzed
      using multivariate logistic regression. The incidence proportion of BDI was
      calculated by dividing the number of cases by the number of cholecystectomies.
      MAIN OUTCOME MEASURES: Relative risks were estimated using odds ratios with 95%
      confidence intervals, and incidence proportion was used to describe incidence.
      RESULTS: Among 152 776 cholecystectomies, 613 reconstructed BDIs (0.40%) were
      identified. Older age and male sex were positively associated with BDI, whereas
      intraoperative cholangiography was negatively associated with BDI. The incidence
      proportion of BDI was 0.40% from 1987 to 1990, decreased to 0.32% from 1991 to
      1995, and increased to 0.47% from 1996 to 2001. The mean yearly hospital volume
      did not affect the risk of BDI. CONCLUSIONS: Older age and male sex increased the
      risk of BDI, whereas intraoperative cholangiography was protective. There was a
      small to moderate long-term increase in the risk of BDI after the introduction of
      laparoscopic cholecystectomy compared with the pre-laparoscopic era.

PMID- 17178964
TI  - Peripheral vascular disease and outcomes following coronary artery bypass graft
      surgery.
AB  - HYPOTHESIS: There is an increased operative risk in patients with a history of
      peripheral vascular disease (PVD) who undergo coronary artery bypass grafting
      (CABG). There are also outcome differences associated with these patients.
      DESIGN: A study from a 10-year hospitalization cohort with prospective data
      collection. SETTING: Multiple hospitals in the Greater Cincinnati area with 1
      surgical group of cardiac surgeons. PARTICIPANTS: Cases were CABG patients with
      PVD, which was defined as having a history of type 1 neurologic injury, prior
      vascular surgery, or current vascular disease (n = 1561). Controls were CABG
      patients without PVD (n = 6328). INTERVENTIONS: The study examined 42 potential
      confounding risk factors and 16 outcome variables. RESULTS: Twenty-nine potential
      risk factors were found to be significantly different between CABG patients with
      and without PVD. Twenty-six confounding risk factors were correlated with 3
      factors. Logistic regression analysis showed that even after controlling for sex,
      significant associative disorders, and other procedures, CABG patients with PVD
      still experienced more arrhythmias requiring treatment (odds ratio [OR], 1.7; 95%
      confidence interval [CI], 1.03-1.33; P = .01), neurological complications (OR,
      1.7; 95% CI, 1.43-2.07; P<.001), pulmonary complications (OR, 1.4; 95% CI, 1.23
      1.62; P<.001), low output (OR, 1.3; 95% CI, 1.09-1.45; P = .001), and
      intraoperative complications (OR, 1.39; 95% CI, 1.06-1.83; P = .02). CONCLUSIONS:
      Patients with a PVD history undergoing CABG had more coexistent risk factors.
      These patients also exhibited higher rates of cardiac, systemic, renal,
      neurologic, and pulmonary complications.

PMID- 17178965
TI  - Preoperative positron emission tomography to evaluate potentially resectable
      hepatic colorectal metastases.
AB  - HYPOTHESIS: Positron emission tomography (PET) influences clinical management in
      the preoperative evaluation of patients with hepatic metastases from colorectal
      cancer. DESIGN: Prospective cohort study. SETTING: Academic tertiary care center.
      PATIENTS: From January 1, 2000, through December 31, 2002, 71 consecutive
      patients referred with potentially resectable hepatic metastases based on
      conventional imaging findings underwent PET or PET with computed tomography in
      the subsequent preoperative evaluation. INTERVENTION: Performance of hepatic
      resection was based on the results of the overall preoperative evaluation. MAIN
      OUTCOME MEASURES: Concordance with conventional imaging findings, identification
      of additional findings, and change in clinical management were analyzed. RESULTS:
      The PET findings confirmed the lesions identified by conventional imaging
      techniques in 64 (90%) of the patients. Additional lesions were identified on PET
      in 23 patients (32%). The information obtained by PET resulted in a change in
      clinical management in 17 cases (24%). False-positive PET findings occurred in 6
      patients (8%), whereas false understaging occurred in 11 (15%). In no cases did
      PET findings have an adverse impact on patient outcome. CONCLUSIONS: Positron
      emission tomography provides useful information in the selection of patients with
      hepatic metastases from colorectal cancer being considered for surgical therapy.
      Such improved selection may serve to reduce the number of unnecessary surgical
      explorations and result in improved long-term survival in patients undergoing
      resection. Positron emission tomography should be integrated into the routine
      preoperative evaluation of patients being considered for hepatic resection of
      colorectal metastases.

PMID- 17178966
TI  - Comparable survival in patients with unresectable hepatocellular carcinoma
      treated by radiofrequency ablation or transarterial chemoembolization.
AB  - HYPOTHESIS: The survival benefits of radiofrequency ablation (RFA) and
      transarterial chemoembolization (TACE) are similar for patients with unresectable
      hepatocellular carcinoma amenable to either treatment. DESIGN: Retrospective
      comparative study. SETTING: Tertiary care institution. PATIENTS: From February
      22, 2001, to March 10, 2004, 91 patients with unresectable hepatocellular
      carcinoma (tumor diameter <5 cm and <4 tumor nodules) treated by either TACE or
      RFA were analyzed from a prospective database. MAIN OUTCOME MEASURES: The
      treatment-related morbidity, mortality, overall survival, and time to disease
      progression. RESULTS: Forty patients received TACE and 51 patients received RFA
      during the study period. Demographic data were comparable in both groups of
      patients. The treatment-related morbidities of TACE and RFA were 10% and 28%,
      respectively (P = .04). There was no treatment-related mortality in either group.
      There was 1 patient (2%) with complete tumor remission in the TACE group, and the
      complete ablation rate in the RFA group was 96%. The time to disease progression
      was similar in both groups (P = .95). The overall survival rates at 1 and 2 years
      were 80% and 58%, respectively, in the TACE group and 82% and 72%, respectively,
      in the RFA group (P = .21). CONCLUSIONS: The overall survival and time for
      disease progression were similar in both groups of patients. In terms of the
      survival result, the efficacies of RFA and TACE were comparable for patients with
      unresectable hepatocellular carcinoma.

PMID- 17178967
TI  - Surgical outcomes in human immunodeficiency virus-infected patients in the era of
      highly active antiretroviral therapy.
AB  - HYPOTHESIS: Matched patients who test positive or negative for human
      immunodeficiency virus (HIV) who are undergoing comparable operations have
      similar complication rates and outcomes. DESIGN: A retrospective study of
      surgical outcomes in HIV-infected and matched HIV-noninfected patients. Baseline
      information including HIV-related laboratory results, complications, and
      mortality was collected from printed and electronic records through 12
      postoperative months. SETTING: Kaiser Permanente Medical Care Program-Northern
      California, an integrated health organization with more than 3 million members,
      including more than 5000 HIV-infected members. PATIENTS: From July 1,1997,
      through June 30, 2002, HIV-infected members undergoing surgical procedures were
      matched 1:1 with HIV-noninfected patients undergoing surgical procedures by type,
      location, and year of surgery as well as by sex and age. Surgical procedures
      studied included appendectomy, arthrotomy or arthroscopy, bowel resection,
      cholecystectomy, cardiothoracic procedures, hernia repair, hysterectomy, hip or
      knee replacement, laparoscopy or laparotomy, and mammoplasty. MAIN OUTCOME
      MEASURES: Complications and mortality through 12 postoperative months,
      comparisons between HIV-infected and HIV-noninfected patients using matched-pair
      analyses, and HIV-infected cohort data were analyzed using the Fisher exact test
      and logistic regression. RESULTS: Of 332 HIV-infected-HIV-noninfected pairs (mean
      age, 46.7 years; male sex, 91%), more than 95.0% were followed up through 12
      postoperative months or until their deaths. Pairs had similar comorbidities,
      length of hospital stay, and number of postoperative surgical visits (P>.05, all
      variables). Among HIV-infected patients, the median years with HIV infection was
      8.4 years; median CD4 T-cell count was 379/microL; 61.5% of these patients had an
      HIV RNA level less than 500 copies per milliliter; and 68% were receiving highly
      active antiretroviral therapy. Various complications were no more frequent among
      HIV-infected than in HIV-noninfected patients (11.1% vs 10.2%; P = .79), except
      for pneumonia (P = .04). There were more deaths within the 12 postoperative
      months in HIV-infected patients (10/332 vs 2/332; P = .02); 2 patients died 30
      days or less after being operated on. Among HIV-infected patients, viral load of
      30 000 copies per milliliter or more was associated with increased complications
      (adjusted odds ratio, 2.95; P = .007), but a CD4 cell count less than 200/muL was
      not associated with poorer outcomes. CONCLUSIONS: The HIV-infected patients had
      more incidences of postoperative pneumonia and higher 12-month mortality,
      although other operative outcomes were comparable for HIV-infected and HIV
      noninfected patients. Viral suppression to fewer than 30 000 copies per
      milliliter reduced surgical complications.

PMID- 17178968
TI  - Induction chemoradiation for rectal cancer.
AB  - OBJECTIVE: To review the application, outcome, and recent developments of
      neoadjuvant chemoradiation therapy with respect to rectal cancer. DATA SOURCES
      AND STUDY SELECTION: Articles written in English after 1980 selected from MEDLINE
      and PubMed from the National Library of Medicine. Case reports were excluded.
      There were no other criteria for exclusion of published information pertaining to
      this topic. DATA EXTRACTION AND SYNTHESIS: Articles were obtained and organized
      from MEDLINE and PubMed as well as the reference lists of pertinent literature.
      CONCLUSIONS: Published reports have demonstrated that neoadjuvant chemoradiation
      improves survival and decreases local recurrence in patients with stage II and
      III rectal cancers. It is anticipated that advances and technical developments in
      both chemotherapy and radiation therapy will lead to improved oncologic results
      with decreased toxic side effects.

PMID- 17178969
TI  - Surgery in Mongolia.
AB  - Western-style medicine in Mongolia was introduced in 1922. Today the health
      service structure is well adapted to the needs of the country. Surgery in
      Mongolia is performed by more than 300 surgeons who serve a population of 2.5
      million people. The differences in geographical and settlement conditions create
      significant disparities in health needs between rural and urban populations. In
      this report we give an overview of the development and current status of medical
      service, disease patterns, and medical educational systems, including surgical
      specialty training.

PMID- 17178970
TI  - Image of the month--retroperitoneal schwannoma.

PMID- 17178971
TI  - Image of the month--leiomyosarcoma of the breast.

PMID- 17178972
TI  - Cost-reduction model for treatment of pancreatic leak following distal
      pancreatectomy.

PMID- 17178974
TI  - Chronic treatment with long-acting nifedipine reduces vasoconstriction to
      endothelin-1 in essential hypertension.
AB  - Essential hypertension is associated with enhanced biological activity of
      endothelin-1 (ET-1) and impaired endothelium-dependent vasodilatation.
      Dihydropyridine calcium antagonists have antioxidant activity in vitro, and they
      improve endothelial function in vivo. We tested whether calcium antagonists also
      influence the biological activity of ET-1 in essential hypertensive (EH) patients
      in the presence and absence of hypercholesterolemia. In 9 healthy subjects
      (normotensive [NT] subjects, age: 48.3+/-7.6 years; blood pressure: 118+/
      8.6/69+/-5.4 mm Hg) and 21 EH subjects (age: 50.0+/-7.8 years; blood pressure:
      164.4+/-5.4/103.8+/-4.4 mm Hg), we studied forearm blood flow and its
      modification induced by intrabrachial administration of ET-1, phenylephrine,
      acetylcholine, and sodium nitroprusside at baseline and after 24 weeks of
      treatment with a nifedipine gastrointestinal therapeutic system (30 to 60 mg per
      day). At baseline, the first dose of ET-1 (0.5 microg/100 mL of forearm tissue
      per minute) caused a slight vasodilatation in NT but not in EH subjects, whereas
      the following higher doses caused a comparable dose-dependent vasoconstriction in
      EH and NT subjects. The effect of acetylcholine was significantly reduced in EH
      as compared with NT subjects. In contrast, sodium nitroprusside and phenylephrine
      had similar effects in NT and EH subjects. After chronic treatment with the
      nifedipine gastrointestinal therapeutic system, the vasoconstrictor effect
      induced by both ET-1 and phenylephrine was significantly blunted, whereas the
      response to acetylcholine was significantly increased and the vasodilation to
      sodium nitroprusside unchanged. Hypercholesterolemic EH subjects showed a further
      reduced response to acetylcholine compared with normocholesterolemic EH subjects,
      and the nifedipine gastrointestinal therapeutic system restored the vasodilation
      to acetylcholine in this subgroup. In conclusion, in EH subjects, chronic
      treatment with a long-acting dihydropyridine calcium antagonist not only exhibits
      a blood pressure-lowering effect but also reduces ET-1-induced vasoconstriction
      and improves endothelium-dependent vasodilation. Those vasculoprotective effects
      may importantly contribute to a reduction in major clinical events seen during
      treatment with these compounds.

PMID- 17178975
TI  - Fall and rise of polypharmacy?

PMID- 17178976
TI  - Low-dose quadruple antihypertensive combination: more efficacious than individual
      agents--a preliminary report.
AB  - Increasingly combined antihypertensive agents are being used in practice to
      enhance control and improve compliance. To determine whether a capsule containing
      a quarter of the standard dose of 4 antihypertensive agents has greater efficacy
      than the standard dose of each individually, we prospectively randomized 108
      untreated white hypertensive patients (55% male) aged 50+/-1 years (mean+/-SEM),
      with mean blood pressure 160+/-1/96+/-1 mm Hg. Patients received amlodipine (5
      mg; n=22), atenolol (50 mg; n=20), bendroflumethiazide (2.5 mg; n=22), captopril
      (50 mg twice daily; n=22) or a capsule containing each of the 4 above at one
      quarter dosage (n=22) in a parallel group design for 4 weeks. Blood pressure was
      measured using a semiautomated device (Omron 705), and the reduction in mean
      arterial pressure with the combined preparation was compared with that of the
      individual components. Statistical analysis used ANOVA and Tukey-Kramer honestly
      significant difference for multiple comparisons. The reduction in mean arterial
      pressure with the combination (19+/-2 mm Hg) was significantly greater than that
      with individual agents amlodipine (10+/-2 mm Hg; P<0.005), atenolol (10+/-2 mm
      Hg; P<0.005), bendroflumethiazide (6+/-1 mm Hg; P<0.005), and captopril (11+/-1
      mm Hg; P<0.01). In addition, the percentage reduction in systolic (18+/-1 mm Hg;
      P<0.005) and diastolic (17+/-2 mm Hg; P=0.06) blood pressure was greater with the
      combination. More patients achieved a blood pressure of <140/90 mm Hg with the
      combination (60%) than any individual drug (15% to 45%; P<0.05). A low-dose
      combination of 4 agents representing 4 classes of standard antihypertensive
      agents was more efficacious than a standard single dose of each agent
      individually.

PMID- 17178977
TI  - Salt intake in children: increasing concerns?

PMID- 17178978
TI  - Left atrial size and risk of major cardiovascular events during antihypertensive
      treatment: losartan intervention for endpoint reduction in hypertension trial.
AB  - The influence of left atrial size on cardiovascular events during
      antihypertensive treatment has not been reported previously from a long-term,
      prospective, randomized hypertension treatment trial. We recorded left atrial
      diameter by annual echocardiography and cardiovascular events in 881 hypertensive
      patients (41% women) with electrocardiographic left ventricular hypertrophy aged
      55 to 80 (mean: 66) years during a mean of 4.8 years of randomized losartan- or
      atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in
      Hypertension Study. During follow-up, a total of 88 primary end points (combined
      cardiovascular death, myocardial infarction, or stroke) occurred. In Cox
      regression, baseline left atrial diameter/height predicted incidence of
      cardiovascular events (hazard ratio: 1.98 per cm/m [95% CI: 1.02 to 3.83 per
      cm/m]; P=0.042) adjusted for significant effects of Framingham risk score and
      history of atrial fibrillation. Greater left atrial diameter reduction during
      follow-up was associated with greater reduction in left ventricular hypertrophy,
      absence of new-onset atrial fibrillation or mitral regurgitation during follow
      up, and losartan-based treatment (B=-0.13+/-0.03 cm/m; P<0.001) in multiple
      linear regression, adjusting for baseline left atrial diameter/height. However,
      in time-varying Cox regression analysis, left atrial diameter reduction was not
      independent of left ventricular hypertrophy regression in predicting
      cardiovascular events during follow-up. In conclusion, left atrial
      diameter/height predicts risk of cardiovascular events independent of other
      clinical risk factors in hypertensive patients with left ventricular hypertrophy
      and may be useful in pretreatment clinical assessment of cardiovascular risk in
      these patients.

PMID- 17178979
TI  - Successful treatment of necrobiosis lipoidica diabeticorum with photodynamic
      therapy.

PMID- 17178980
TI  - Rate of growth in melanomas: characteristics and associations of rapidly growing
      melanomas.
AB  - OBJECTIVES: To investigate the spectrum of growth rates in melanomas and to
      identify clinical associations of rapidly growing melanomas. DESIGN: Clinical
      interview, skin examination, and pathology review. SETTING: Three tertiary
      melanoma referral centers and 2 private dermatology practices. PATIENTS: A total
      of 404 consecutive patients with invasive primary cutaneous melanomas. MAIN
      OUTCOME MEASURE: A surrogate for rate of growth in primary invasive melanoma was
      calculated as the ratio of Breslow thickness to time to melanoma development
      based on a previously reported assessment tool. RESULTS: One third of the
      melanomas grew 0.5 mm per month or more. The median monthly growth rate was 0.12
      mm for superficial spreading melanomas, 0.13 mm for lentigo maligna melanomas,
      and 0.49 mm for nodular melanomas. Rapid tumor growth was associated with tumor
      thickness (<or=1 mm, geometric mean ratio [GMR] = 1.0; 1.01-4 mm, GMR = 3.9; and
      >4 mm, GMR = 12.1) and mitotic rate (<1/mm(2), GMR = 1.0; 1-4/mm(2), GMR = 2.9; 5
      10/mm(2), GMR = 6.1; and >10/mm(2), GMR = 9.7). Rapid tumor growth occurred more
      often in males (GMR = 1.7), elderly individuals (>or=70 years old, GMR = 2.8),
      and patients with fewer melanocytic nevi (n<50, GMR = 2.0) and fewer freckles
      (GMR = 2.5). Rapidly growing melanomas were more often symmetrical (GMR = 2.5),
      elevated (GMR = 1.4), amelanotic (GMR = 1.7), regular in border (GMR = 2.5), and
      symptomatic (GMR = 1.7). CONCLUSIONS: Rapid growth of primary cutaneous melanomas
      is associated with aggressive histologic features and atypical clinical features.
      It occurs more frequently in elderly men and individuals with fewer nevi and
      fewer freckles.

PMID- 17178981
TI  - Cutaneous lymphoid hyperplasia presenting as a solitary facial nodule: clinical,
      histopathological, immunophenotypical, and molecular studies.
AB  - OBJECTIVE: To elucidate the clinicopathological, immunophenotypical, and
      molecular characteristics of cutaneous lymphoid hyperplasia presenting as a
      solitary facial nodule. DESIGN: Retrospective study. SETTING: University
      dermatology department. PATIENTS: Three patients with a solitary facial nodule
      were studied clinically, histologically, immunophenotypically, and molecularly
      for T-cell receptor and immunoglobulin heavy chain gene rearrangements. MAIN
      OUTCOME MEASURES: Histological, immunophenotypical, and molecular characteristics
      in relation to the clinical outcome. RESULTS: Histologically, dense diffuse
      lymphocytic infiltrates were present throughout the dermis, occasionally
      extending into the subcutaneous fat and the epidermis and hair follicles. Small
      lymphocytes predominated, but in 2 cases there were also medium to large atypical
      lymphocytes, with some blastlike lymphocytes. The lymphocytic population was
      mixed with more CD3(+) T cells than CD20(+) B cells, without germinal centers.
      There were more CD4(+) than CD8(+) cells, and some of the T cells stained for the
      memory T-cell marker CD45RO. Numerous CD68(+) histiocytes were scattered or
      formed small aggregates, and in 1 case small granulomas and many scattered S100
      protein-positive and CD1a(+)dendritic cells were present. In addition, several
      polytypic plasma cells, eosinophils, and extravasated erythrocytes were found.
      Immunostaining for CD10, CD21, CD30, CD56, and BCL6 was negative. The Ki-67
      proliferation index was relatively low (5%-10%). Results of the T-cell receptor
      gene rearrangement studies were positive in 2 cases, 1 of which also harbored
      clonal B cells. Serologic test results for Borrelia burgdorferi, Borrelia
      afzelii, and Borrelia garinii were negative in all 3 cases. Two lesions regressed
      spontaneously after an incisional biopsy, and none of the cases showed recurrence
      or extracutaneous spread during a follow-up period of 5.0 to 5.5 years.
      CONCLUSIONS: Cutaneous lymphoid hyperplasia that presents as a solitary facial
      nodule may share clinical, cytological, immunophenotypical, and molecular
      features with both benign reactive lymphocytic infiltrates and cutaneous
      lymphomas, and therefore a careful clinical and therapeutic approach is
      warranted.

PMID- 17178982
TI  - An open-label adrenal suppression study of 0.1% fluocinonide cream in pediatric
      patients with atopic dermatitis.
AB  - OBJECTIVE: To assess the potential of a superhigh-potency 0.1% fluocinonide cream
      to suppress the hypothalamic-pituitary-adrenal (HPA) axis in pediatric patients
      with atopic dermatitis. DESIGN: A multicenter, multiple-dose, open-label safety
      study in 4 age cohorts with 0.1% fluocinonide cream applied once or twice daily
      for 2 weeks. SETTING: Clinical outpatient setting. PATIENTS: Patients with
      moderate to severe atopic dermatitis with 20% or more of the body surface area
      involved were included in the study. Each cohort began only after evaluation of
      the preceding cohort: ages 12 to younger than 18 years (cohort 1); 6 to younger
      than 12 years (cohort 2); 2 to younger than 6 years (cohort 3); and 3 months to
      younger than 2 years (cohort 4). MAIN OUTCOME MEASURES: Assessment of HPA axis
      suppression, local and systemic adverse events, and change in disease status from
      baseline. RESULTS: Suppression of the HPA axis was not observed in any patient
      treated once daily for the 2 youngest cohorts. Suppression was observed in 1 (7%)
      of 15 and 2 (12%) of 16 patients in the fluocinonide twice-daily group in cohorts
      1 and 2, respectively. In all 4 cohorts, more than 90% of patients in the
      fluocinonide once-daily and twice-daily groups showed improvement in their
      disease status. CONCLUSIONS: Once-daily treatment with 0.1% fluocinonide cream
      for 2 weeks does not result in HPA axis suppression under the conditions of this
      study. Once-daily applications provided similar or better efficacy as twice-daily
      applications with a lower risk of HPA axis suppression. The frequency of HPA axis
      suppression is no greater in younger children than in older children. TRIAL
      REGISTRATION: isrctn.org Identifier: ISRCTN71227633.

PMID- 17178984
TI  - Thermoregulatory sweat testing in patients with erythromelalgia.
AB  - OBJECTIVES: To examine the results of thermoregulatory sweat testing in patients
      with erythromelalgia and to compare them with the results of other
      neurophysiologic tests of small-fiber nerve function. DESIGN: Retrospective
      study. SETTING: Tertiary referral center. PATIENTS: Thirty-two consecutive
      patients with erythromelalgia who had thermoregulatory sweat testing in addition
      to vascular and nerve testing. INTERVENTION: The following information was
      abstracted for each patient: demographics, clinical presentation, and results of
      thermoregulatory sweat testing, vascular (noninvasive) testing, and nerve testing
      (electromyography and autonomic reflex screen, including quantitative sudomotor
      axon reflex test). MAIN OUTCOME MEASURES: Results of thermoregulatory sweat
      testing to evaluate small-fiber neuropathy, compared with other tools used to
      estimate small-fiber neuropathy. RESULTS: Thermoregulatory sweat testing results
      were abnormal in 28 (88%) of 32 patients, and quantitative sudomotor axon reflex
      test results were abnormal in 22 patients (69%). Abnormalities noted on
      thermoregulatory sweat testing varied from local hypohidrosis or anhidrosis to
      global anhidrosis. Global or almost-global anhidrosis was present in 8 patients
      (25%); in 19 patients (59%) the anhidrosis was distal, and 1 other patient (3%)
      had a less specific pattern of anhidrosis (multifocal or regional). The area of
      anhidrosis generally corresponded to the area that was symptomatic of the
      erythromelalgia. CONCLUSIONS: Small-fiber neuropathy is prevalent in most
      patients with erythromelalgia. Thermoregulatory sweat testing is a sensitive and
      useful marker of small-fiber neuropathy in these patients.

PMID- 17178983
TI  - Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis:
      a randomized assessor-blind controlled trial.
AB  - OBJECTIVE: To determine the efficacy and safety of imiquimod in combination with
      meglumine antimoniate in treating cutaneous leishmaniasis. DESIGN: Prospective,
      randomized, assessor-blind, parallel-design, placebo-controlled trial. SETTING:
      Two primary care health clinics. PATIENTS: One hundred nineteen patients (59
      patients in the imiquimod group and 60 in the placebo group) were included in the
      study. INTERVENTIONS: Patients were randomly assigned to receive a combined 4
      week course of imiquimod or placebo with meglumine antimoniate treatment (20
      mg/kg of pentavalent antimony daily for 2 weeks) in an endemic area of Leishmania
      tropica. MAIN OUTCOME MEASURES: The primary end point was clinical cure, defined
      as more than 75% reduction in the size of lesions compared with baseline at week
      8. RESULTS: At the end of the 4-week treatment period, clinical cure was similar
      in both groups (11 patients [18.6%] in the imiquimod-treated group vs 18 patients
      [30.0%] in the placebo group) (P = .15). Four weeks after the end of treatment,
      26 patients (44.1%) and 29 patients (48.3%) in the imiquimod-treated and placebo
      groups, respectively, were cured (P = .64). Pruritus and burning sensation were
      reported by 3 patients treated with imiquimod and by no patients treated with
      placebo. CONCLUSION: This study showed no beneficial effect of combining a 4-week
      course of treatment with 5% imiquimod cream and a standard course of treatment
      with meglumine antimoniate in patients with cutaneous leishmaniasis in an endemic
      area of L tropica. TRIAL REGISTRATION: isrctn.org Identifier:ISRCTN77659407 and
      Cochrane Skin Group Identifier: CSG Trial No. 32.

PMID- 17178985
TI  - Phenotype, genotype, and sustained response to anakinra in 22 patients with
      autoinflammatory disease associated with CIAS-1/NALP3 mutations.
AB  - OBJECTIVE: To characterize the multisystem chronic inflammatory phenotype,
      dermatopathologic features, and response to therapy with interleukin 1 receptor
      antagonist (anakinra) in patients with mutations in the CIAS-1/NALP3 gene.
      DESIGN: Retrospective review of medical records and evaluation of histologic
      findings. SETTING: The National Amyloidosis Centre, London, and a tertiary
      referral clinic for urticaria. PATIENTS: Twenty-two individuals from 13 families
      with autoinflammatory disease associated with CIAS-1/NALP3 mutations. MAIN
      OUTCOME MEASURES: Phenotype, genotype, skin histologic findings, and response to
      treatment with anakinra. RESULTS: Five heterozygous missense mutations were
      identified in CIAS-1/NALP3. Skin histologic findings revealed marked vascular
      dilatation and neutrophilic infiltration involving small vessels and eccrine
      glands. Serologic evidence of intense inflammation was present in untreated
      patients, with median serum amyloid A protein and C-reactive protein levels of
      141 and 38 mg/L, respectively. Fifteen patients received anakinra for up to 39
      months, all of whom achieved serologic remission and complete resolution of
      fever, rash, conjunctivitis, and rheumatic symptoms, without any adverse effects.
      Six patients had AA (reactive systemic) amyloidosis, 2 of whom died of renal
      failure complications before interleukin 1-inhibiting therapy was available; 1
      patient underwent renal transplantation and remains clinically well taking
      anakinra, and in the remaining 3 patients, anakinra therapy resulted in remission
      of their nephrotic syndrome. CONCLUSIONS: Anakinra therapy was well tolerated and
      has sustained efficacy on dermatologic and rheumatic manifestations in these
      patients with CIAS-1/NALP3 mutations. This treatment also resulted in resolution
      of AA amyloidosis-associated nephrotic syndrome in all affected patients.

PMID- 17178986
TI  - Effect of neonatal phototherapy on melanocytic nevus count in children.
AB  - BACKGROUND: Melanocytic nevus is the strongest risk factor for the development of
      cutaneous melanoma. Fair skin and exposure to UV light, especially in childhood,
      are correlated with the development of childhood nevi. OBJECTIVE: To assess the
      role of blue light neonatal phototherapy used to treat hyperbilirubinemia in
      nevus acquisition in childhood. DESIGN: Case-control prospective study. SETTING:
      University hospital. PARTICIPANTS: Fifty-eight children were included in this
      study. Selection criteria included the following: age, 8 to 9 years; and skin
      type, less than IV by Fitzpatrick classification (ie, brown, always tans, rarely
      burns). The case group consisted of 18 children exposed to neonatal phototherapy
      (mostly intensive phototherapy) retrospectively found by review of consecutive
      neonatal medical records at Saint-Antoine Hospital, Paris, France. The control
      group was composed of 40 nonexposed children consecutively recruited from a
      public school in the same geographic area. MAIN OUTCOME MEASURES: Total body
      nevus count in children, phenotypic characteristics, solar exposure, and
      demographic data were assessed by the same dermatologist. RESULTS: A comparison
      of both groups showed that the number of nevi larger than 2 mm was significantly
      higher in the exposed group. The mean (SD) nevus count was 3.5 (3.05; median,
      3.0) per child in the exposed group, compared with 1.45 (1.99; median, 1.0) per
      child in the nonexposed group (P(mean) = .02 and P(median) = .01). Multivariate
      analysis confirmed these results, with a statistically significant correlation
      with nevus count, especially with nevi 2 to 5 mm in greatest diameter. The
      association between neonatal phototherapy and nevus count was not significant for
      nevi smaller than 2 mm or larger than 5 mm. Solar exposure, especially during
      vacations, was strongly associated with total nevus count and all nevus sizes (2
      5 mm, <2 mm, and >5 mm). At univariate analysis, hair color was significantly
      associated with nevus size smaller than 2 mm (P(mean) = .03). CONCLUSIONS:
      Intensive neonatal phototherapy is a strong risk factor for nevus development in
      childhood. While childhood development of nevi is correlated with fair skin and
      solar light exposure, and having many nevi is a recognized risk factor in persons
      with melanoma, we must be careful not to equate childhood nevi development in
      response to neonatal phototherapy with an individual's risk of developing
      melanoma. The treatment of hyperbilirubinemia remains neonatal phototherapy.
      Exposed children should undergo dermatologic preventive measures and surveillance
      for the development of melanoma.

PMID- 17178987
TI  - Superficial venous thrombophlebitis as the initial manifestation of
      hypereosinophilic syndrome: study of the first 3 cases.
AB  - BACKGROUND: Superficial venous thrombophlebitis (SVT), often perceived as benign,
      can coexist with hypercoagulable states. Predisposing risk factors for SVT are
      similar to those observed for deep venous thrombosis. Association of eosinophilia
      with SVT is a rare situation that can reveal neoplasia, malignant blood
      disorders, or vasculitis, but it has never been described in hypereosinophilic
      syndrome (HES). We herein describe the clinical and biological features, outcome,
      and response to therapy of 3 patients with SVT associated with eosinophilia that
      revealed HES. OBSERVATIONS: Superficial venous thrombophlebitis was the initial
      manifestation of HES in all 3 patients. The mean eosinophil count at diagnosis
      was 2.4 x 10(3)/muL. All patients received corticosteroids and anticoagulants as
      the initial treatment, with marked improvement of SVT and return of the
      eosinophil count to reference limits. All patients experienced relapse and
      remained dependent on corticosteroid therapy. Two patients received interferon
      alfa with dramatic regression of SVT, allowing a decrease in the dose of
      corticosteroids. CONCLUSIONS: We report, to our knowledge, the first 3 cases of
      SVT related to HES. Superficial venous thrombophlebitis was difficult to treat,
      with dependence on corticosteroid therapy and partial efficacy of anticoagulant
      and antiplatelet therapy. Interferon alfa was effective in preventing relapse of
      SVT related to HES. Mechanisms implied in this thrombogenesis are multiple and
      remain speculative.

PMID- 17178988
TI  - Keratosis pilaris rubra: a common but underrecognized condition.
AB  - BACKGROUND: Keratosis pilaris is a common skin disorder of childhood that often
      improves with age. Less common variants of keratosis pilaris include keratosis
      pilaris atrophicans and atrophodermia vermiculata. OBSERVATIONS: In this case
      series from dermatology practices in the United States, Canada, Israel, and
      Australia, the clinical characteristics of 27 patients with keratosis pilaris
      rubra are described. Marked erythema with follicular prominence was noted in all
      patients, most commonly affecting the lateral aspects of the cheeks and the
      proximal arms and legs, with both more marked erythema and widespread extent of
      disease than in keratosis pilaris. The mean age at onset was 5 years (range,
      birth to 12 years). Sixty-three percent of patients were male. No patients had
      atrophy or scarring from their lesions. Various treatments were used, with
      minimal or no improvement in most cases. CONCLUSIONS: Keratosis pilaris rubra is
      a variant of keratosis pilaris, with more prominent erythema and with more
      widespread areas of skin involvement in some cases, but without the atrophy or
      hyperpigmentation noted in certain keratosis pilaris variants. It seems to be a
      relatively common but uncommonly reported condition.

PMID- 17178989
TI  - Novel KIND1 gene mutation in Kindler syndrome with severe gastrointestinal tract
      involvement.
AB  - BACKGROUND: Kindler syndrome (online Mendelian Inheritance in Man No. 173650) is
      an autosomal recessive genodermatosis characterized by acral trauma-induced
      blistering that improves with age and by progressive poikiloderma in later life.
      Other clinical features include photosensitivity, webbing of the fingers and
      toes, nail dystrophy, periodontal disease, and mucosal alterations. Aside from
      esophageal or anal stenosis, gastrointestinal tract involvement seems to be rare
      in Kindler syndrome. Recently, mutations in the KIND1 gene that encodes for the
      membrane-associated protein kindlin-1 have been identified. Kindlin-1 links the
      actin cytoskeleton to the extracellular matrix and is supposed to have cell
      signaling functions owing to different functional domains. In particular, a
      domain with high homology to 4.1/ezrin/radixin/moesin (FERM) proteins is closely
      related to the sequences of talin that mediate integrin binding and therefore may
      play a role in integrin-dependent processes such as cell growth, differentiation,
      and apoptosis. OBSERVATION: Complete loss of this multifunctional protein in our
      patient with Kindler syndrome resulted in severe gastrointestinal tract
      involvement with hemorrhagic colitis. Mucosa of the descending and sigmoid colon
      and the rectum showed erosions and ulcers with pseudomembranous alterations of an
      overall highly vulnerable mucosa. Mutation analysis revealed a homozygous status
      for the novel mutation 20/21delTT in exon 2 of the KIND1 gene resulting in a
      preterminal stop codon creating a nonfunctional peptide 17 amino acids in length.
      CONCLUSION: Because of our experience with this and another patient, we propose
      that gastrointestinal tract involvement should be looked at more frequently in
      Kindler syndrome.

PMID- 17178990
TI  - Dermoscopy patterns of halo nevi.
AB  - BACKGROUND: Halo nevi (HN) are benign melanocytic nevi surrounded by a
      depigmented area (halo). This study aims to evaluate the dermoscopic features of
      HN and their changes during digital dermoscopic follow-up and to investigate the
      frequency of the halo phenomenon in a series of melanomas. OBSERVATIONS: In a
      retrospective study, digital dermoscopic images of HN from patients who attended
      the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical
      University of Graz, between October 1, 1997, and March 31, 2004, were reviewed
      and classified by dermoscopic morphologic criteria. For HN that were followed up
      with digital dermoscopy, the percentages of changes in the size of the nevus and
      halo components were calculated. In addition, digital dermoscopic images of
      histopathologically confirmed melanomas obtained from the same database were
      reviewed for the presence of an encircling halolike depigmentation. We classified
      138 HN in 87 patients (mean age, 22.4 years). The most common dermoscopic
      structures were the globular and/or homogeneous patterns in more than 80% of HN.
      Follow-up of 33 HN revealed considerable size reduction of the nevus component,
      but this was not associated with significant structural changes. Of a total of
      475 melanomas, only 2 revealed an encircling halo, but both displayed clear-cut
      melanoma-specific patterns according to dermoscopy. CONCLUSIONS: Halo nevi
      exhibit the characteristic dermoscopic features of benign melanocytic nevi,
      represented by globular and/or homogeneous patterns that are typically observed
      in children and young adults. Halo nevi reveal considerable changes of area over
      time during digital dermoscopic follow-up, albeit their structural patterns
      remain unchanged. For this reason and because melanoma with halolike
      depigmentation, despite being rare, additionally exhibits melanoma-specific
      dermoscopic criteria, the role of digital dermoscopic follow-up in the diagnosis
      of HN is insignificant.

PMID- 17178991
TI  - Bug Buster for head lice: is it effective?

PMID- 17178992
TI  - Growth rate, early detection, and prevention of melanoma: melanoma epidemiology
      revisited and future challenges.

PMID- 17178993
TI  - Taking ethics seriously in cosmetic dermatology.

PMID- 17178994
TI  - Spiny hyperkeratotic projections on the face and extremities of a kidney
      transplant recipient.

PMID- 17178995
TI  - Hypopigmented macules in an Indian man.

PMID- 17178996
TI  - Crusted swollen lower lip.

PMID- 17178997
TI  - Pustule-studded plaques after abrasion injury.

PMID- 17178998
TI  - Academic dermatology.

PMID- 17178999
TI  - Evidence-based dermatology: some problems with research.

PMID- 17179000
TI  - Clinical evaluation of bug busting: response to suggestions of bias.

PMID- 17179001
TI  - Deja vu all over again.

PMID- 17179002
TI  - Alopecia areata during treatment with biologic agents.

PMID- 17179003
TI  - Development of alopecia areata universalis in a patient receiving adalimumab.

PMID- 17179004
TI  - Lymphocytic infiltration of the skin Jessner-Kanof after treatment with a
      hydroquinone-containing bleaching cream.

PMID- 17179005
TI  - Facial hypertrichosis induced by Cetuximab, an anti-EGFR monoclonal antibody.

PMID- 17179006
TI  - Zygomycosis of the penis due to Rhizopus oryzae successfully treated with
      surgical debridement and a combination of high-dose liposomal and topical
      amphotericin B.

PMID- 17179007
TI  - Ulceration of the arm attributed to a spider bite and treated with intravenous
      hydrogen peroxide: a cautionary tale.

PMID- 17179008
TI  - Dactinomycin-induced cutaneous toxic effects during treatment of choriocarcinoma.

PMID- 17179009
TI  - Unilateral aquagenic wrinkling of the palms associated with aspirin intake.

PMID- 17179010
TI  - Pigmented purpuric dermatosis associated with creatine supplementation.

PMID- 17179012
TI  - Use of dermoscopy to visualize punctate hemorrhages and onycholysis in
      "playstation thumb".

PMID- 17179011
TI  - Pseudomonas aeruginosa ecthyma gangrenosum and facial cellulitis complicating
      carbimazole-induced agranulocytosis.

PMID- 17179015
TI  - The peripheral clearing zone: sometimes a subtle clue for the recognition of
      melanoma.

PMID- 17179013
TI  - Hair casts and cutaneous spicules in multiple myeloma.

PMID- 17179016
TI  - Statins and the risk of lung, breast, and colorectal cancer in the elderly.
AB  - BACKGROUND: Although most randomized trials and meta-analyses suggest a slight or
      no increase in the risk of cancer in statin users, results from observational
      studies have been conflicting, and some have even suggested a large protective
      effect of statins on certain cancers. Long-term statin users tend to be
      healthier, less frail, and more adherent to therapy than nonusers, however. This
      could explain such apparent "protective" effects. METHODS AND RESULTS: We
      conducted the present cohort study by linking data from a large state drug
      benefit program with cancer registry data and Medicare healthcare utilization
      data. We identified all initiators of statins; initiators of glaucoma
      medications, another preventive drug, served as a comparison group. Outcomes
      included all registry-identified cases of colorectal, lung, and breast cancer.
      Multivariable Cox proportional models were used to adjust for confounding.
      Patient characteristics were similar in both groups, but statin initiators
      (n=24,439) were slightly younger and used some services more frequently than
      glaucoma drug initiators (n=7284). The mean follow-up was 2.9 years, with the
      longest follow-up being 8.4 years. Incidence rates of colorectal, lung, and
      breast cancers in both groups were very similar to rates in the general
      population. Adjusted hazard ratios were 0.96 (95% CI, 0.70 to 1.31) for
      colorectal cancer, 1.11 (95% CI, 0.77 to 1.60) for lung cancer, and 0.99 (95% CI,
      0.74 to 1.33) for breast cancer. CONCLUSIONS: These data from a large population
      of typical older patients who began using statins indicate that it is unlikely
      that statins confer a clinically important decrease or increase in the risk of
      colorectal, lung, or breast cancer over the durations studied.

PMID- 17179017
TI  - Localization and quantification of platelet-rich thrombi in large blood vessels
      with near-infrared fluorescence imaging.
AB  - BACKGROUND: Imaging of thrombus formation in vivo has been limited by the
      inability to directly visualize and measure thrombi in large blood vessels in
      real time. Near-infrared light, with its superior tissue penetration and reduced
      scatter, could potentially solve this problem. METHODS AND RESULTS: Platelets
      were labeled with the near-infrared fluorophore IR-786. Optimal total
      fluorescence yield occurred at 6 attomoles of IR-786 per platelet. IR-786-labeled
      platelets were tested for their ability to detect thrombus formation in large
      animal model systems relevant to common human vascular procedures. Invisible near
      infrared light did not distort the surgical field in any way, and even after
      optimization of per-platelet fluorescent yield, platelets remained fully
      functional. Intravenous infusion of just 3.6x10(10) labeled platelets into a 35
      kg Yorkshire pig permitted thrombus visualization, with a signal-to-background
      ratio > or = 2, for at least 2 hours in coronary, carotid, and femoral vessels.
      Platelet-rich, actively growing clots were monitored in real time and quantified
      with respect to size and kinetics after injury to vessels, cutaneous incisions,
      intravascular stent insertion, or introduction of embolic coils. Similarly,
      formed clots were monitored in real time during thrombolysis with streptokinase
      and heparin. Vessel patency was assessed independently with a second near
      infrared fluorescent blood pool agent. CONCLUSIONS: IR-786-labeled platelets
      provide sensitive, specific, and real-time visualization of thrombi in thick
      walled blood vessels. In addition to immediate application in cardiac,
      transplant, and vascular surgery, the mechanisms that underlie thrombus formation
      in large blood vessels can now be investigated.

PMID- 17179018
TI  - Greater fish, fruit, and vegetable intakes are related to lower incidence of
      venous thromboembolism: the Longitudinal Investigation of Thromboembolism
      Etiology.
AB  - BACKGROUND: Little is known about the role of dietary intake in the development
      of deep vein thrombosis or pulmonary embolus (venous thromboembolism [VTE]).
      Homocysteine, factor VIII, and von Willebrand factor levels, risk factors for
      VTE, are influenced by dietary intake. We tested the hypothesis that foods rich
      in B vitamins and omega-3 fatty acids are negatively associated and meat intake
      is positively associated with incidence of VTE. METHODS AND RESULTS: In a
      prospective study over 12 years, 14,962 middle-aged adults participating in the
      Atherosclerosis Risk in Communities study were followed up for incident VTE. All
      hospitalizations were identified, and 196 VTEs were validated by chart review. A
      food frequency questionnaire assessed dietary intake at baseline and year 6. In
      separate proportional hazards regression analyses, risk of developing VTE was
      computed across quintiles of selected nutrients, major food groups, and the
      Western diet pattern, with adjustment for demographic and lifestyle factors, body
      mass index, and diabetes. Hazard ratios and 95% confidence intervals of VTE
      incidence across quintiles of fruit and vegetable intake were 1.0 (reference),
      0.73 (0.48 to 1.11), 0.57 (0.37 to 0.90), 0.47 (0.29 to 0.77), and 0.59 (0.36 to
      0.99) (P(trend)=0.03). Eating fish 1 or more times per week was associated with
      30% to 45% lower incidence of VTE for quintiles 2 to 5 compared with quintile 1,
      suggestive of a threshold effect. Hazard ratios of VTE across quintiles of red
      and processed meat intake were 1.0, 1.24 (0.78 to 1.98), 1.21 (0.74 to 1.98),
      1.09 (0.64 to 1.87), and 2.01 (1.15 to 3.53) (P(trend)=0.02). Hazard ratios were
      attenuated only slightly after adjustment for factors VIIc and VIIIc and von
      Willebrand factor. CONCLUSIONS: A diet including more plant food and fish and
      less red and processed meat is associated with a lower incidence of VTE.

PMID- 17179019
TI  - Prospective familial assessment in dilated cardiomyopathy: cardiac autoantibodies
      predict disease development in asymptomatic relatives.
AB  - BACKGROUND: In autoimmune disorders, circulating autoantibodies identify healthy
      relatives at risk years before clinical presentation. Healthy relatives of
      patients with dilated cardiomyopathy (DCM) who have echocardiographic changes,
      including left ventricular enlargement or depressed fractional shortening at
      baseline, have increased medium-term risk for DCM development. Approximately one
      third of relatives have serum anti-heart autoantibodies (AHAs) at baseline; we
      intended to assess their potential role in predicting DCM development. METHODS
      AND RESULTS: Baseline evaluation, including electrocardiography,
      echocardiography, and AHA, was performed in 592 asymptomatic relatives of 169
      consecutive DCM patients (291 males and 301 females; mean age 36+/-16 years).
      Relatives were classified in accordance with published echocardiographic
      criteria; those who did not have DCM were followed up (median of 58 months). DCM
      among relatives was diagnosed by echocardiography at follow-up. Of the 592
      individuals evaluated, 77% were assessed as normal, 4.4% as having DCM, and 19%
      as possibly affected on the basis of depressed fractional shortening without
      ventricular dilatation in 17 and left ventricular enlargement without systolic
      dysfunction in 94. Five-year follow-up of 311 relatives revealed that 26 had
      progressed (13 to DCM, 11 to left ventricular enlargement, and 2 to depressed
      fractional shortening). Relatives who developed DCM were more frequently AHA
      positive than those who did not (69% versus 37%, P=0.02). Five-year probability
      of progression to DCM, among normal or possibly affected relatives, was higher in
      AHA-positive cases (P=0.03). By Cox regression, positive AHAs at baseline were
      independent predictors of progression (RR 2.26, CI 1 to 5.1, P=0.03).
      CONCLUSIONS: Among healthy relatives of DCM patients, AHAs are independent
      predictors of disease development within 5 years.

PMID- 17179020
TI  - Atherosclerotic renovascular disease in older US patients starting dialysis, 1996
      to 2001.
AB  - BACKGROUND: Temporal trends regarding the epidemiology of atherosclerotic
      renovascular disease (ARVD) in dialysis populations are poorly defined. METHODS
      AND RESULTS: United States Renal Data System data were used to identify patients
      aged 67 years or older at dialysis inception between 1996 and 2001 (n=146,973).
      Medicare claims in the preceding 2 years were used to identify ARVD and
      revascularization procedures. Prior ARVD rose from 7.1% to 11.2% between 1996 and
      2001 (adjusted odds ratio [AOR], 1.68). Other associations included hypertensive
      end-stage renal disease (ESRD; AOR, 2.21), ESRD network (AOR, 0.44 in network 17
      versus 1.00 in network 1), peripheral vascular disease (AOR, 1.65), black race
      (AOR, 0.44), urologic cause of ESRD (AOR, 0.57), age >85 years (AOR, 0.58),
      substance dependency (AOR, 0.62), and inability to ambulate or transfer (AOR,
      0.67). The proportion of ARVD patients undergoing revascularization rose from
      14.6% to 16.7% between 1996 and 2001 (AOR, 1.27). Other associations included
      hypertension (AOR, 2.10), ESRD network (AOR, 2.07 for network 13 versus 1.00 in
      network 1), age >85 years (AOR, 0.53), and black race (AOR, 0.54). The rise in
      ARVD was not reflected in the proportion of patients with renovascular disease
      listed as cause of ESRD on the Medical Evidence Report at dialysis inception
      (5.5% in 1996, 5.0% in 2001). CONCLUSIONS: ARVD diagnoses have become more common
      in older patients beginning dialysis therapy. The association of demographic
      factors including age, race, and geographic residence with utilization patterns
      suggests possible barriers to care.

PMID- 17179021
TI  - Is dual-chamber programming inferior to single-chamber programming in an
      implantable cardioverter-defibrillator? Results of the INTRINSIC RV (Inhibition
      of Unnecessary RV Pacing With AVSH in ICDs) study.
AB  - BACKGROUND: The INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AVSH in
      ICDs) study tested the hypothesis that dual-chamber rate-responsive (DDDR) with
      atrioventricular search hysteresis (AVSH) 60-130 programming is not inferior to
      single-chamber (VVI)-40 programming in an implantable cardioverter defibrillator
      with respect to all-cause mortality and heart failure hospitalizations using an
      equivalence margin of 5%. METHODS AND RESULTS: At 108 centers, 1530 patients with
      an implantable cardioverter defibrillator indication received a VITALITY AVT
      (Guidant Corporation, St. Paul, Minn) implantable cardioverter defibrillator
      programmed consistently to DDDR AVSH 60-130 for the first week. Of those, 988
      patients with <20% right ventricular pacing at 1 week were randomized to DDDR
      AVSH 60-130 or to VVI-40 programming. Among those randomized, 502 were assigned
      to DDDR AVSH and 486 to VVI. Groups were similar with regard to coronary disease
      (68%), gender (21% female), and New York Heart Association functional class >I
      (79%). A total of 32 patients (6.4%) in the DDDR AVSH arm and 46 patients (9.5%)
      in the VVI arm died or were hospitalized for heart failure during a mean follow
      up of 10.4 months (relative risk=0.67, P=0.072 in favor of DDDR AVSH). DDDR AVSH
      was not inferior to VVI programming (P<0.001). All-cause mortality was not
      significantly different between the DDDR AVSH arm (3.6%) and the VVI arm (5.1%;
      P=0.23). The mean percent right ventricular pacing in the DDDR AVSH arm was 10%
      (median 4%) versus 3% (median 0%) in the VVI arm. CONCLUSIONS: In the INTRINSIC
      RV trial, among those randomized, DDDR AVSH was associated with similar outcomes
      as with VVI backup pacing.

PMID- 17179022
TI  - Sildenafil improves exercise hemodynamics and oxygen uptake in patients with
      systolic heart failure.
AB  - BACKGROUND: Heart failure (HF) is frequently associated with dysregulation of
      nitric oxide-mediated pulmonary vascular tone. Sildenafil, a type 5
      phosphodiesterase inhibitor, lowers pulmonary vascular resistance in pulmonary
      hypertension by augmenting intracellular levels of the nitric oxide second
      messenger, cyclic GMP. We tested the hypothesis that a single oral dose of
      sildenafil (50 mg) would improve exercise capacity and exercise hemodynamics in
      patients with chronic systolic HF through pulmonary vasodilation. METHODS AND
      RESULTS: Thirteen patients with New York Heart Association class III HF underwent
      assessment of right heart hemodynamics, gas exchange, and first-pass radionuclide
      ventriculography at rest and with cycle ergometry before and 60 minutes after
      administration of 50 mg of oral sildenafil. Sildenafil reduced resting pulmonary
      arterial pressure, systemic vascular resistance, and pulmonary vascular
      resistance, and increased resting and exercise cardiac index (P<0.05 for all)
      without altering mean arterial pressure, heart rate, or pulmonary capillary wedge
      pressure. Sildenafil reduced exercise pulmonary arterial pressure, pulmonary
      vascular resistance, and pulmonary vascular resistance/systemic vascular
      resistance ratio, which indicates a selective pulmonary vasodilator effect with
      exercise. Peak VO2 increased (15+/-9%) and ventilatory response to CO2 output
      (VE/VCO2 slope) decreased (16+/-5%) after sildenafil treatment. Improvements in
      right heart hemodynamics and exercise capacity were confined to patients with
      secondary pulmonary hypertension (rest pulmonary arterial pressure >25 mm Hg).
      CONCLUSIONS: The present study shows that in patients with systolic HF, type 5
      phosphodiesterase inhibition with sildenafil improves peak VO2, reduces VE/VCO2
      slope, and acts as a selective pulmonary vasodilator during rest and exercise in
      patients with HF and pulmonary hypertension.

PMID- 17179023
TI  - Promotion of faster weight gain in infants born small for gestational age: is
      there an adverse effect on later blood pressure?
AB  - BACKGROUND: Being born small for gestational age is associated with later risk
      factors for cardiovascular disease, such as high blood pressure. Promotion of
      postnatal growth has been proposed to ameliorate these effects. There is evidence
      in animals and infants born prematurely, however, that promotion of growth by
      increased postnatal nutrition increases rather than decreases later
      cardiovascular risk. We report the long-term impact of growth promotion in term
      infants born small for gestational age (birth weight <10th percentile). METHODS
      AND RESULTS: Blood pressure was measured at 6 to 8 years in 153 of 299 (51%) of a
      cohort of children born small for gestational age and randomly assigned at birth
      to receive either a standard or a nutrient-enriched formula. The enriched formula
      contained 28% more protein than standard formula and promoted weight gain.
      Diastolic and mean (but not systolic) blood pressure was significantly lower in
      children assigned to standard compared with nutrient-enriched formula (unadjusted
      mean difference for diastolic blood pressure, -3.2 mm Hg; 95% CI, -5.8 to -0.5;
      P=0.02) independent of potential confounding factors (adjusted difference, -3.5
      mm Hg; P=0.01). In observational analyses, faster weight gain in infancy was
      associated with higher later blood pressure. CONCLUSIONS: In the present
      randomized study targeted to investigate the effect of early nutrition on long
      term cardiovascular health, we found that a nutrient-enriched diet increased
      later blood pressure. These findings support an adverse effect of relative
      "overnutrition" in infancy on long-term cardiovascular disease risk, have
      implications for the early origins of cardiovascular disease hypothesis, and do
      not support the promotion of faster weight gain in infants born small for
      gestational age.

PMID- 17179024
TI  - Nonfinancial incentives for quality: a policy statement from the American Heart
      Association.

PMID- 17179026
TI  - Images in cardiovascular medicine. A quadricuspid aortic valve with severe aortic
      regurgitation.

PMID- 17179025
TI  - Essential features of a surveillance system to support the prevention and
      management of heart disease and stroke: a scientific statement from the American
      Heart Association Councils on Epidemiology and Prevention, Stroke, and
      Cardiovascular Nursing and the Interdisciplinary Working Groups on Quality of
      Care and Outcomes Research and Atherosclerotic Peripheral Vascular Disease.

PMID- 17179027
TI  - Images in cardiovascular medicine. Acute coronary syndrome due to intramural
      hematoma.

PMID- 17179028
TI  - Images in cardiovascular medicine. Definitive diagnosis of obstructed total
      anomalous pulmonary venous drainage in a critically ill newborn with high
      resolution computed tomography.

PMID- 17179029
TI  - Letter by Brilakis and Banerjee regarding article, "Impact of internal mammary
      artery conduit on long-term outcomes after percutaneous intervention of saphenous
      vein graft".

PMID- 17179030
TI  - Centres of excellence in cardiology: the Onassis Center.

PMID- 17179031
TI  - Measuring progress in resuscitation: it's time for a better tool.

PMID- 17179032
TI  - Racial and ethnic differences in blood pressure: biology and sociology.

PMID- 17179033
TI  - Cardiopulmonary resuscitation: history, current practice, and future direction.

PMID- 17179034
TI  - The cardiovascular disease continuum validated: clinical evidence of improved
      patient outcomes: part I: Pathophysiology and clinical trial evidence (risk
      factors through stable coronary artery disease).

PMID- 17179035
TI  - The cardiovascular disease continuum validated: clinical evidence of improved
      patient outcomes: part II: Clinical trial evidence (acute coronary syndromes
      through renal disease) and future directions.

PMID- 17179036
TI  - Synthetic small molecule furin inhibitors derived from 2,5-dideoxystreptamine.
AB  - Furin plays a crucial role in embryogenesis and homeostasis and in diseases such
      as Alzheimer's disease, cancer, and viral and bacterial infections. Thus,
      inhibition of furin may provide a feasible and promising approach for therapeutic
      intervention of furin-mediated disease mechanisms. Here, we report on a class of
      small molecule furin inhibitors based on 2,5-dideoxystreptamine. Derivatization
      of 2,5-dideoxystreptamine by the addition of guanidinylated aryl groups yielded a
      set of furin inhibitors with nanomolar range potency against furin when assayed
      in a biochemical cleavage assay. Moreover, a subset of these furin inhibitors
      protected RAW 264.7 macrophage cells from toxicity caused by furin-dependent
      processing of anthrax protective antigen. These inhibitors were found to behave
      as competitive inhibitors of furin and to be relatively specific for furin.
      Molecular modeling revealed that these inhibitors may target the active site of
      furin as they showed site occupancy similar to the alkylating inhibitor decanoyl
      Arg-Val-Lys-Arg-CH(2)Cl. The compounds presented here are bona fide synthetic
      small molecule furin inhibitors that exhibit potency in the nanomolar range,
      suggesting that they may serve as valuable tools for studying furin action and
      potential therapeutics agents for furin-dependent diseases.

PMID- 17179037
TI  - PSD-95 and PKC converge in regulating NMDA receptor trafficking and gating.
AB  - Neuronal NMDA receptors (NMDARs) colocalize with postsynaptic density protein-95
      (PSD-95), a putative NMDAR anchoring protein and core component of the PSD, at
      excitatory synapses. PKC activation and PSD-95 expression each enhance NMDAR
      channel opening rate and number of functional channels at the cell surface. Here
      we show in Xenopus oocytes that PSD-95 and PKC potentiate NMDA gating and
      trafficking in a nonadditive manner. PSD-95 and PKC each enhance NMDA channel
      activity, with no change in single-channel conductance, reversal potential or
      mean open time. PSD-95 and PKC each potentiate NMDA channel opening rate
      (k(beta)) and number of functional channels at the cell surface (N), as indicated
      by more rapid current decay and enhanced charge transfer in the presence of the
      open channel blocker MK-801. PSD-95 and PKC each increase NMDAR surface
      expression, as indicated by immunofluorescence. PKC potentiates NMDA channel
      function and NMDAR surface expression to the same final absolute values in the
      absence or presence of PSD-95. Thus, PSD-95 partially occludes PKC potentiation.
      We further show that Ser-1462, a putative phosphorylation target within the PDZ
      binding motif of the NR2A subunit, is required for PSD-95-induced potentiation
      and partial occlusion of PKC potentiation. Coimmunoprecipitation experiments with
      cortical neurons in culture indicate that PKC activation promotes assembly of NR2
      with NR1, and that the newly assembled NMDARs are not associated with PSD-95.
      These findings predict that synaptic scaffolding proteins and protein kinases
      convergently modulate NMDAR gating and trafficking at synaptic sites.

PMID- 17179039
TI  - Nisin-induced changes in Bacillus morphology suggest a paradigm of antibiotic
      action.
AB  - Nisin is a small cationic lanthionine antibiotic produced by Lactococcus lactis.
      During its antimicrobial action, it targets intermediates in the bacterial cell
      wall biosynthesis, lipid II, and undecaprenyl pyrophosphate. Here, we report
      results from electron microscopic investigations of the effects of lethal nisin
      doses on Bacillus subtilis cell morphology. Bacterial membranes were
      permeabilized shortly after B. subtilis was incubated with nisin, but this did
      not lead to immediate cell death. Cell division, as well as other life functions,
      persisted over at least half an hour after nisin was added. Slower bacterial
      elongation, consistent with cell envelope inhibition and accelerated division,
      resulted in cell-length reduction. Abnormal morphogenesis near the division site
      suggests this to be the primary site of nisin action. Morphological changes are
      characteristic of deregulation of a filamentous cell envelope protein, Mbl, and
      the division-inhibiting Min system. We propose a previously undescribed model, in
      which the lethal action of nisin against B. subtilis starts with membrane
      permeabilization and is followed by accelerated cell division, cell envelope
      inhibition, and aberrant cell morphogenesis.

PMID- 17179038
TI  - The structural basis for the mutagenicity of O(6)-methyl-guanine lesions.
AB  - Methylating agents are widespread environmental carcinogens that generate a broad
      spectrum of DNA damage. Methylation at the guanine O(6) position confers the
      greatest mutagenic and carcinogenic potential. DNA polymerases insert cytosine
      and thymine with similar efficiency opposite O(6)-methyl-guanine (O6MeG). We
      combined pre-steady-state kinetic analysis and a series of nine x-ray crystal
      structures to contrast the reaction pathways of accurate and mutagenic
      replication of O6MeG in a high-fidelity DNA polymerase from Bacillus
      stearothermophilus. Polymerases achieve substrate specificity by selecting for
      nucleotides with shape and hydrogen-bonding patterns that complement a canonical
      DNA template. Our structures reveal that both thymine and cytosine O6MeG base
      pairs evade proofreading by mimicking the essential molecular features of
      canonical substrates. The steric mimicry depends on stabilization of a rare
      cytosine tautomer in C.O6MeG-polymerase complexes. An unusual electrostatic
      interaction between O-methyl protons and a thymine carbonyl oxygen helps
      stabilize T.O6MeG pairs bound to DNA polymerase. Because DNA methylators
      constitute an important class of chemotherapeutic agents, the molecular
      mechanisms of replication of these DNA lesions are important for our
      understanding of both the genesis and treatment of cancer.

PMID- 17179041
TI  - Air pollution and climate change both reduce Indian rice harvests.

PMID- 17179040
TI  - Mesodermal cell displacements during avian gastrulation are due to both
      individual cell-autonomous and convective tissue movements.
AB  - Gastrulation is a fundamental process in early development that results in the
      formation of three primary germ layers. During avian gastrulation, presumptive
      mesodermal cells in the dorsal epiblast ingress through a furrow called the
      primitive streak (PS), and subsequently move away from the PS and form adult
      tissues. The biophysical mechanisms driving mesodermal cell movements during
      gastrulation in amniotes, notably warm-blooded embryos, are not understood. Until
      now, a major challenge has been distinguishing local individual cell-autonomous
      (active) displacements from convective displacements caused by large-scale (bulk)
      morphogenetic tissue movements. To address this problem, we used multiscale, time
      lapse microscopy and a particle image velocimetry method for computing tissue
      displacement fields. Immunolabeled fibronectin was used as an in situ marker for
      quantifying tissue displacements. By imaging fluorescently labeled mesodermal
      cells and surrounding extracellular matrix simultaneously, we were able to
      separate directly the active and passive components of cell displacement during
      gastrulation. Our results reveal the following: (i) Convective tissue motion
      contributes significantly to total cell displacement and must be subtracted to
      measure true cell-autonomous displacement; (ii) Cell-autonomous displacement
      decreases gradually after regression from the PS; and (iii) There is an
      increasing cranial-to-caudal (head-to-tail) cell-autonomous motility gradient,
      with caudal cells actively moving away from the PS faster than cranial cells.
      These studies show that, in some regions of the embryo, total mesodermal cell
      displacements are mostly due to convective tissue movements; thus, the data have
      profound implications for understanding cell guidance mechanisms and tissue
      morphogenesis in warm-blooded embryos.

PMID- 17179042
TI  - Profile of Edward L. Miles.

PMID- 17179043
TI  - Illuminating membrane fusion.

PMID- 17179044
TI  - Introduced cryptic species of parasites exhibit different invasion pathways.
AB  - Sometimes infectious agents invade and become established in new geographic
      regions. Others may be introduced yet never become established because of the
      absence of suitable hosts in the new region. This phenomenon may be particularly
      true for the many parasites with complex life cycles, where various life stages
      require different host species. Homogenization of the world's biota through human
      mediated invasions may reunite hosts and parasites, resulting in disease
      outbreaks in novel regions. Here we use molecular genetics to differentiate
      invasion pathways for two digenean trematode parasites and their exotic host, the
      Asian mud snail, Batillaria attramentaria. All of the snail haplotypes found in
      introduced populations in North America were identical to haplotypes common in
      the areas of Japan that provided oysters for cultivation in North America,
      supporting the hypothesis that the snails were introduced from Japan with seed
      oysters. Two cryptic trematode species were introduced to North American
      populations in high frequencies. We found a marked reduction of genetic variation
      in one of these species, suggesting it experienced a bottleneck or founder event
      comparable to that of the host snail. In contrast, no genetic variation was lost
      in the other parasite species. We hypothesize that this parasite was and is
      dispersed naturally by migratory shorebirds and was able to establish only after
      the host snail, B. attramentaria, was introduced to North America. Evaluation of
      the nature of invasion pathways and postinvasion consequences will aid mitigation
      of spreading diseases of humans, livestock, and wildlife in an increasingly
      globalized world.

PMID- 17179045
TI  - Determination of solvent content in cavities in IL-1beta using experimentally
      phased electron density.
AB  - The extent to which water is present within apolar cavities in proteins remains
      unclear. In the case of interleukin-1beta (IL-1beta), four independent structures
      solved by x-ray crystallography indicate that water is not present in the central
      apolar cavity. In contrast, results from NMR spectroscopy suggest that water has
      high occupancy within the cavity but is positionally disordered, making it
      undetectable by standard crystallographic methods. A theoretically based
      crystallographic-phase refinement technique also suggested that there was the
      equivalent of two fully occupied water molecules within the apolar cavity. To
      resolve these discrepancies we sought to obtain an experimentally phased electron
      density map that was free of possible bias caused by mathematical modeling of the
      protein or the solvent. By combining native diffraction data with multiple
      wavelength anomalous data from a platinum derivative, accurate phases were
      obtained. Using these experimental phases, we estimate that occupancy of the
      apolar cavity in IL-1beta by solvent is close or equal to zero. Polar cavities in
      the protein that contain ordered solvent molecules serve as internal controls.

PMID- 17179046
TI  - Role of protein frame and solvent for the redox properties of azurin from
      Pseudomonas aeruginosa.
AB  - We have coupled hybrid quantum mechanics (density functional theory; Car
      Parrinello)/molecular mechanics molecular dynamics simulations to a grand
      canonical scheme, to calculate the in situ redox potential of the Cu(2+) + e(-) -
      > Cu(+) half reaction in azurin from Pseudomonas aeruginosa. An accurate
      description at atomistic level of the environment surrounding the metal-binding
      site and finite-temperature fluctuations of the protein structure are both
      essential for a correct quantitative description of the electronic properties of
      this system. We report a redox potential shift with respect to copper in water of
      0.2 eV (experimental 0.16 eV) and a reorganization free energy lambda = 0.76 eV
      (experimental 0.6-0.8 eV). The electrostatic field of the protein plays a crucial
      role in fine tuning the redox potential and determining the structure of the
      solvent. The inner-sphere contribution to the reorganization energy is
      negligible. The overall small value is mainly due to solvent rearrangement at the
      protein surface.

PMID- 17179047
TI  - Interstrain transfer of the large pathogenicity island (PAPI-1) of Pseudomonas
      aeruginosa.
AB  - The large Pseudomonas aeruginosa pathogenicity island PAPI-1 of strain PA14 is a
      cluster of 108 genes that encode a number of virulence features. We demonstrate
      that, in a subpopulation of cells, PAPI-1 can exist in an extrachromosomal
      circular form after precise excision from its integration site within the 3'
      terminus of the tRNA(Lys) gene. Circular PAPI-1 can reintegrate into either of
      the two tRNA(Lys) genes, including the one that was used for integration of small
      pathogenicity island PAPI-2 in strain PA14. The excision requires PAPI-1-encoded
      integrase, a member of the tyrosine recombinase family. PAPI-1 Soj contains the
      conserved domains of proteins that are related to chromosome and plasmid
      partition. soj plays a role in maintaining PAPI-1 and mutations in soj result in
      the loss of PAPI-1 from P. aeruginosa. We further demonstrate that, during
      coculture, the PAPI-1-containing strains are able to transfer it into P.
      aeruginosa recipient strains that do not harbor this island naturally. After
      transfer, PAPI-1 integrates into either of the two tRNA(Lys) genes. PAPI-1
      encompasses many features of mobile elements, including mobilization and
      maintenance modules. Together with the virulence determinants, PAPI-1 plays an
      important role in the evolution of P. aeruginosa, by expanding its natural
      habitat from soil and water to animal and human infections.

PMID- 17179048
TI  - Single-stranded nucleic acid-induced helical self-assembly of alkynylplatinum(II)
      terpyridyl complexes.
AB  - Single-stranded nucleic acids, which carry multiple negative charges in an
      aqueous medium at near neutral pH, are found to induce the aggregation and self
      assembly of the positively charged alkynylplatinum(II) terpyridyl complexes via
      electrostatic binding of the platinum complexes to the single-stranded nucleic
      acids, as revealed by the appearance of new UV-vis absorption and emission bands
      upon addition of single-stranded nucleic acids to a buffer solution of the
      complex. Changes in the intensity and pattern of circular dichroism (CD)
      spectroscopy are also observed, many of which are consistent with the assembly of
      the platinum complexes into helical structures, via metal...metal and pi...pi
      stacking interactions. The induced spectroscopic property changes are found to
      depend on the structural properties of the nucleic acids.

PMID- 17179049
TI  - Mechanism of allosteric regulation of transglutaminase 2 by GTP.
AB  - Allosteric regulation is a fundamental mechanism of biological control. Here, we
      investigated the allosteric mechanism by which GTP inhibits cross-linking
      activity of transglutaminase 2 (TG2), a multifunctional protein, with postulated
      roles in receptor signaling, extracellular matrix assembly, and apoptosis. Our
      findings indicate that at least two components are involved in functionally
      coupling the allosteric site and active center of TG2, namely (i) GTP binding to
      mask a conformationally destabilizing switch residue, Arg-579, and to facilitate
      interdomain interactions that promote adoption of a compact, catalytically
      inactive conformation and (ii) stabilization of the inactive conformation by an
      uncommon H bond between a cysteine (Cys-277, an active center residue) and a
      tyrosine (Tyr-516, a residue located on a loop of the beta-barrel 1 domain that
      harbors the GTP-binding site). Although not essential for GTP-mediated inhibition
      of cross-linking, this H bond enhances the rate of formation of the inactive
      conformer.

PMID- 17179050
TI  - Anisotropy of cell adhesive microenvironment governs cell internal organization
      and orientation of polarity.
AB  - Control of the establishment of cell polarity is an essential function in tissue
      morphogenesis and renewal that depends on spatial cues provided by the
      extracellular environment. The molecular role of cell-cell or cell-extracellular
      matrix (ECM) contacts on the establishment of cell polarity has been well
      characterized. It has been hypothesized that the geometry of the cell adhesive
      microenvironment was directing cell surface polarization and internal
      organization. To define how the extracellular environment affects cell polarity,
      we analyzed the organization of individual cells plated on defined micropatterned
      substrates imposing cells to spread on various combinations of adhesive and
      nonadhesive areas. The reproducible normalization effect on overall cell
      compartmentalization enabled quantification of the spatial organization of the
      actin network and associated proteins, the spatial distribution of microtubules,
      and the positioning of nucleus, centrosome, and Golgi apparatus. By using
      specific micropatterns and statistical analysis of cell compartment positions, we
      demonstrated that ECM geometry determines the orientation of cell polarity axes.
      The nucleus-centrosome orientations were reproducibly directed toward cell
      adhesive edges. The anisotropy of the cell cortex in response to the adhesive
      conditions did not affect the centrosome positioning at the cell centroid. Based
      on the quantification of microtubule plus end distribution we propose a working
      model that accounts for that observation. We conclude that, in addition to
      molecular composition and mechanical properties, ECM geometry plays a key role in
      developmental processes.

PMID- 17179051
TI  - Identification of quantitative trait loci affecting body composition in a mouse
      intercross.
AB  - Gravimetric analysis and dual energy x-ray absorptiometry densitometry were used
      to determine lean, fat, and bone tissue traits in a F(2) mouse population from a
      C57BL/6J and CASA/Rk intercross (B6CASAF2). These traits were used in a linkage
      analysis to identify quantitative trait loci that affect body composition.
      Linkage mapping showed that body weight (BW) loci on proximal chromosome 2
      occurred in the same region as body length, lean tissue mass, and bone mineral
      content and on chromosome 13 in the same region as lean tissue mass, bone mineral
      density, and bone mineral content. Fat-related loci occurring on mid-chromosome 2
      near 60 cM, proximal chromosome 6, and mid-chromosome 10 were distinct from BW,
      lean tissue, and bone tissue loci. In B6CASAF2 females, heterozygotes and CASA/Rk
      homozygotes at the chromosome 6 locus marker had higher body fat percentages, and
      this locus was responsible for 11% of the variance for body fat percentage.
      Female heterozygotes and C57BL/6J homozygotes at the chromosome 15 locus marker
      had higher bone mineral densities, and this locus could explain 8% of that
      trait's variance. A survey of the literature did not reveal any previous reports
      of fat-specific loci in the chromosomal 10 region near 42 cM reported in this
      study. The results of this study indicate that BW and BMI have limited usefulness
      as phenotypes in linkage or association studies when used as obesity phenotypes.

PMID- 17179053
TI  - Enzyme replacement in Fabry disease: the essence is in the kidney.

PMID- 17179054
TI  - Summaries for patients. Treating symptoms of menopause: a study of the
      effectiveness of black cohosh alone and with other herbal therapies or soy.

PMID- 17179052
TI  - Agalsidase-beta therapy for advanced Fabry disease: a randomized trial.
AB  - BACKGROUND: Fabry disease (alpha-galactosidase A deficiency) is a rare, X-linked
      lysosomal storage disorder that can cause early death from renal, cardiac, and
      cerebrovascular involvement. OBJECTIVE: To see whether agalsidase beta delays the
      onset of a composite clinical outcome of renal, cardiovascular, and
      cerebrovascular events and death in patients with advanced Fabry disease. DESIGN:
      Randomized (2:1 treatment-to-placebo randomization), double-blind, placebo
      controlled trial. SETTING: 41 referral centers in 9 countries. PATIENTS: 82
      adults with mild to moderate kidney disease; 74 of whom were protocol-adherent.
      INTERVENTION: Intravenous infusion of agalsidase beta (1 mg per kg of body
      weight) or placebo every 2 weeks for up to 35 months (median, 18.5 months).
      MEASUREMENTS: The primary end point was the time to first clinical event (renal,
      cardiac, or cerebrovascular event or death). Six patients withdrew before
      reaching an end point: 3 to receive commercial therapy and 3 due to positive or
      inconclusive serum IgE or skin test results. Three patients assigned to
      agalsidase beta elected to transition to open-label treatment before reaching an
      end point. RESULTS: Thirteen (42%) of the 31 patients in the placebo group and 14
      (27%) of the 51 patients in the agalsidase-beta group experienced clinical
      events. Primary intention-to-treat analysis that adjusted for an imbalance in
      baseline proteinuria showed that, compared with placebo, agalsidase beta delayed
      the time to first clinical event (hazard ratio, 0.47 [95% CI, 0.21 to 1.03]; P =
      0.06). Secondary analyses of protocol-adherent patients showed similar results
      (hazard ratio, 0.39 [CI, 0.16 to 0.93]; P = 0.034). Ancillary subgroup analyses
      found larger treatment effects in patients with baseline estimated glomerular
      filtration rates greater than 55 mL/min per 1.73 m2 (hazard ratio, 0.19 [CI, 0.05
      to 0.82]; P = 0.025) compared with 55 mL/min per 1.73 m2 or less (hazard ratio,
      0.85 [CI, 0.32 to 2.3]; P = 0.75) (formal test for interaction, P = 0.09). Most
      treatment-related adverse events were mild or moderate infusion-associated
      reactions, reported by 55% of patients in the agalsidase-beta group and 23% of
      patients in the placebo group. LIMITATIONS: The study sample was small. Only one
      third of the patients experienced clinical events, and some patients withdrew
      before experiencing any event. CONCLUSIONS: Agalsidase-beta therapy slowed
      progression to the composite clinical outcome of renal, cardiac, and
      cerebrovascular complications and death compared with placebo in patients with
      advanced Fabry disease. Therapeutic intervention before irreversible organ damage
      may provide greater clinical benefit.

PMID- 17179055
TI  - Summaries for patients. Complications of colonoscopy.

PMID- 17179056
TI  - Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals,
      soy, hormone therapy, or placebo: a randomized trial.
AB  - BACKGROUND: Herbal supplements are widely used for vasomotor symptoms. OBJECTIVE:
      To test the efficacy of 3 herbal regimens and hormone therapy for relief of
      vasomotor symptoms compared with placebo. DESIGN: 1-year randomized, double
      blind, placebo-controlled trial conducted from May 2001 to September 2004.
      SETTING: Group Health, Washington State. PARTICIPANTS: 351 women age 45 to 55
      years with 2 or more vasomotor symptoms per day; 52% of the women were in
      menopausal transition and 48% were postmenopausal. MEASUREMENTS: Rate and
      intensity of vasomotor symptoms (1 = mild to 3 = severe), and Wiklund Vasomotor
      Symptom Subscale. INTERVENTIONS: 1) Black cohosh, 160 mg daily; 2) multibotanical
      with black cohosh, 200 mg daily, and 9 other ingredients; 3) multibotanical plus
      dietary soy counseling; 4) conjugated equine estrogen, 0.625 mg daily, with or
      without medroxyprogesterone acetate, 2.5 mg daily; or 5) placebo. RESULTS:
      Vasomotor symptoms per day, symptom intensity, Wiklund Vasomotor Symptom Subscale
      score did not differ between the herbal interventions and placebo at 3, 6, or 12
      months or for the average over all the follow-up time points (P > 0.05 for all
      comparisons) with 1 exception: At 12 months, symptom intensity was significantly
      worse with the multibotanical plus soy intervention than with placebo (P =
      0.016). The difference in vasomotor symptoms per day between placebo and any of
      the herbal treatments at any time point was less than 1 symptom per day; for the
      average over all the follow-up time points, the difference was less than 0.55
      symptom per day. The difference for hormone therapy versus placebo was -4.06
      vasomotor symptoms per day for the average over all the follow-up time points
      (95% CI, -5.93 to -2.19 symptoms per day; P < 0.001). LIMITATIONS: The trial did
      not simulate the whole-person approach used by naturopathic physicians.
      Differences between treatment groups smaller than 1.5 Vasomotor symptoms per day
      cannot be ruled out. CONCLUSION: Black cohosh used in isolation, or as part of a
      multibotanical regimen, shows little potential as an important therapy for relief
      of vasomotor symptoms. CLINICAL TRIALS REGISTRATION NUMBER: NCT00169299.

PMID- 17179057
TI  - Complications of colonoscopy in an integrated health care delivery system.
AB  - BACKGROUND: Information about colonoscopy complications, particularly
      postpolypectomy bleeding, is limited. OBJECTIVE: To quantify the magnitude and
      severity of colonoscopy complications. DESIGN: Retrospective cohort. SETTING:
      Kaiser Permanente of Northern California. PATIENTS: 16, 318 members 40 years of
      age or older undergoing colonoscopy between January 1994 and July 2002.
      MEASUREMENTS: Electronic records reviewed for serious complications, including
      hospital admission within 30 days of colonoscopy for colonic perforation, colonic
      bleeding, diverticulitis, the postpolypectomy syndrome, or other serious
      illnesses directly related to colonoscopy. RESULTS: 82 serious complications
      occurred (5.0 per 1000 colonoscopies [95% CI, 4.0 to 6.2 per 1000
      colonoscopies]). Serious complications occurred in 0.8 per 1000 colonoscopies
      without biopsy or polypectomy and in 7.0 per 1000 colonoscopies with biopsy or
      polypectomy. Perforations occurred in 0.9 per 1000 colonoscopies (CI, 0.5 to 1.5
      per 1000 colonoscopies) (0.6 per 1000 without biopsy or polypectomy and 1.1 per
      1000 with biopsy or polypectomy). Postbiopsy or postpolypectomy bleeding occurred
      in 4.8 per 1000 colonoscopies with biopsy (CI, 3.6 to 6.2 per 1000
      colonoscopies). Biopsy or polypectomy was associated with an increased risk for
      any serious complication (rate ratio, 9.2 [CI, 2.9 to 29.0] vs. colonoscopy
      without biopsy). Ten deaths (1 attributable to colonoscopy) occurred within 30
      days of the colonoscopy. LIMITATIONS: 99.3% (16 204) of colonoscopies were
      nonscreening examinations. The rate of complications may be lower in a primary
      screening sample. The small number of observed adverse events limited power to
      detect risk factors for complications. CONCLUSIONS: Colonoscopy with biopsy or
      polypectomy is associated with increased risk for complications. Perforation may
      also occur during colonoscopies without biopsies.

PMID- 17179058
TI  - Effect of a mailed brochure on appointment-keeping for screening colonoscopy: a
      randomized trial.
AB  - BACKGROUND: Even when primary care physicians have face-to-face discussions with
      patients before referring them for screening colonoscopy, patient nonadherence
      can be substantial. Often, primary care physicians lack sufficient time to
      educate patients and address their potential misconceptions and fears about this
      procedure. OBJECTIVE: To test whether an informational brochure sent to patients'
      home addresses after referral for screening colonoscopy would increase patient
      completion of the procedure. DESIGN: Randomized, controlled trial. SETTING: 2
      general internal medicine practices affiliated with the University of Colorado
      Health Sciences Center. PATIENTS: 781 consecutive patients 50 years of age or
      older referred by their primary care physicians for screening colonoscopy.
      INTERVENTION: Patients were randomly assigned to receive usual care (control
      group) versus usual care plus an informational brochure (intervention group). The
      brochure was mailed within 10 days of referral for screening colonoscopy; it
      mentioned the name of the patient's primary care physician and encouraged
      patients to schedule a procedure. It also described colorectal cancer and polyps
      and the similar lifetime risks for colorectal cancer for men and women,
      colonoscopy and risk for perforation, the nature of bowel preparation for the
      procedure, and alternative screening tests. MEASUREMENTS: Rates of adherence to
      screening colonoscopy in the 2 study groups. RESULTS: The overall adherence rate
      was 11.7 percentage points (95% CI, 5.1 to 18.4 percentage points) greater in the
      intervention group than in the control group (70.7% vs. 59.0%). Older patients
      were more adherent than younger patients. Patients with low-income insurance
      plans, such as Medicaid, were less adherent despite being sent a brochure.
      LIMITATIONS: The small number of clinical practices and minority patients may
      limit generalizability. In addition, it was not possible to determine the degree
      to which adherence was influenced by a reminder to schedule a procedure versus
      detailed information about colonoscopy. CONCLUSIONS: An inexpensive mailed
      brochure is an effective way to increase patient adherence to primary care
      physician referral for screening colonoscopy.

PMID- 17179059
TI  - New insights into the pathophysiology of chronic myeloid leukemia and imatinib
      resistance.
AB  - Chronic myeloid leukemia (CML) was the first human malignant disease to be linked
      to a single, acquired genetic abnormality. Identification of the BCR-ABL kinase
      fusion protein and its central role in the pathogenesis of CML provided new
      opportunities to develop rational molecular targeted therapies. This review
      provides an update on the underlying pathophysiologies of disease progression and
      imatinib mesylate resistance, leading to the development of new targeted tyrosine
      kinase inhibitors for managing CML. Imatinib, a selective inhibitor of BCR-ABL,
      represents a major success in the era of target-directed cancer chemotherapy.
      However, patients with advanced CML have been less sensitive to therapy and
      responses have been short. In addition, treatment resistance is an emerging
      problem at all disease stages. Insight into factors involved in imatinib
      resistance and disease progression has highlighted a role for such BCR-ABL
      dependent factors as amplification and overexpression of the BCR-ABL gene and the
      emergence of mutant isoforms of BCR-ABL. However, BCR-ABL-independent factors,
      including leukemogenic pathways involving kinases other than BCR-ABL, also play a
      part. In light of the limitations of imatinib against these factors, newer
      tyrosine kinase inhibitors, including dasatinib (a multitargeted kinase inhibitor
      of BCR-ABL and Src family kinases) and nilotinib (AMN107, a selective BCR-ABL
      inhibitor), may provide promising treatment options for patients with CML.

PMID- 17179060
TI  - A randomized trial of alternative medicines for vasomotor symptoms of menopause.

PMID- 17179061
TI  - Trials that matter: can patients with venous thromboembolism be treated with
      fixed-dose subcutaneous unfractionated heparin?

PMID- 17179062
TI  - The veil.

PMID- 17179063
TI  - John Loesch and Harry Goldblatt: two great pioneers in circulation research.

PMID- 17179064
TI  - Questionnaire to distinguish between stress and urge urinary incontinence.

PMID- 17179065
TI  - Questionnaire to distinguish between stress and urge urinary incontinence.

PMID- 17179066
TI  - Questionnaire to distinguish between stress and urge urinary incontinence.

PMID- 17179067
TI  - Rapid purification of RNAs using fast performance liquid chromatography (FPLC).
AB  - We present here an improved RNA purification method using fast performance liquid
      chromatography (FPLC) size-exclusion chromatography in place of denaturing
      polyacrylamide gel electrophoresis (PAGE). The method allows preparation of
      milligram quantities of pure RNA in a single day. As RNA oligonucleotides behave
      differently from globular proteins in the size-exclusion column, we present
      standard curves for RNA oligonucleotides of different lengths on both the
      Superdex 75 column and the Superdex 200 size-exclusion column. Using this
      approach, we can separate monomer from multimeric RNA species, purify the desired
      RNA product from hammerhead ribozyme reactions, and isolate refolded RNA that has
      aggregated after long-term storage. This methodology allows simple and rapid
      purification of RNA oligonucleotides for structural and biophysical studies.

PMID- 17179069
TI  - Type IV procollagen missense mutations associated with defects of the eye,
      vascular stability, the brain, kidney function and embryonic or postnatal
      viability in the mouse, Mus musculus: an extension of the Col4a1 allelic series
      and the identification of the first two Col4a2 mutant alleles.
AB  - The basement membrane is important for proper tissue development, stability, and
      physiology. Major components of the basement membrane include laminins and type
      IV collagens. The type IV procollagens Col4a1 and Col4a2 form the heterotrimer
      [alpha1(IV)]2[alpha2(IV)], which is ubiquitously expressed in basement membranes
      during early developmental stages. We present the genetic, molecular, and
      phenotypic characterization of nine Col4a1 and three Col4a2 missense mutations
      recovered in random mutagenesis experiments in the mouse. Heterozygous carriers
      express defects in the eye, the brain, kidney function, vascular stability, and
      viability. Homozygotes do not survive beyond the second trimester. Ten mutations
      result in amino acid substitutions at nine conserved Gly sites within the
      collagenous domain, one mutation is in the carboxy-terminal noncollagenous
      domain, and one mutation is in the signal peptide sequence and is predicted to
      disrupt the signal peptide cleavage site. Patients with COL4A2 mutations have
      still not been identified. We suggest that the spontaneous intraorbital
      hemorrhages observed in the mouse are a clinically relevant phenotype with a
      relatively high predictive value to identify carriers of COL4A1 or COL4A2
      mutations.

PMID- 17179070
TI  - Maximum-likelihood estimation of allelic dropout and false allele error rates
      from microsatellite genotypes in the absence of reference data.
AB  - The importance of quantifying and accounting for stochastic genotyping errors
      when analyzing microsatellite data is increasingly being recognized. This
      awareness is motivating the development of data analysis methods that not only
      take errors into consideration but also recognize the difference between two
      distinct classes of error, allelic dropout and false alleles. Currently methods
      to estimate rates of allelic dropout and false alleles depend upon the
      availability of error-free reference genotypes or reliable pedigree data, which
      are often not available. We have developed a maximum-likelihood-based method for
      estimating these error rates from a single replication of a sample of genotypes.
      Simulations show it to be both accurate and robust to modest violations of its
      underlying assumptions. We have applied the method to estimating error rates in
      two microsatellite data sets. It is implemented in a computer program, Pedant,
      which estimates allelic dropout and false allele error rates with 95% confidence
      regions from microsatellite genotype data and performs power analysis. Pedant is
      freely available at http://www.stats.gla.ac.uk/ approximately paulj/pedant.html.

PMID- 17179068
TI  - Evaluation of the genomic extent of effects of fixed inversion differences on
      intraspecific variation and interspecific gene flow in Drosophila pseudoobscura
      and D. persimilis.
AB  - There is increasing evidence that chromosomal inversions may facilitate the
      formation or persistence of new species by allowing genetic factors conferring
      species-specific adaptations or reproductive isolation to be inherited together
      and by reducing or eliminating introgression. However, the genomic domain of
      influence of the inverted regions on introgression has not been carefully
      studied. Here, we present a detailed study on the consequences that distance from
      inversion breakpoints has had on the inferred level of gene flow and divergence
      between Drosophila pseudoobscura and D. persimilis. We identified the locations
      of the inversion breakpoints distinguishing D. pseudoobscura and D. persimilis in
      chromosomes 2, XR, and XL. Population genetic data were collected at specific
      distances from the inversion breakpoints of the second chromosome and at two loci
      inside the XR and XL inverted regions. For loci outside the inverted regions, we
      found that distance from the nearest inversion breakpoint had a significant
      effect on several measures of divergence and gene flow between D. pseudoobscura
      and D. persimilis. The data fitted a logarithmic relationship, showing that the
      suppression of crossovers in inversion heterozygotes also extends to loci located
      outside the inversion but close to it (within 1-2 Mb). Further, we detected a
      significant reduction in nucleotide variation inside the inverted second
      chromosome region of D. persimilis and near one breakpoint, consistent with a
      scenario in which this inversion arose and was fixed in this species by natural
      selection.

PMID- 17179071
TI  - Transposition of a fungal miniature inverted-repeat transposable element through
      the action of a Tc1-like transposase.
AB  - The mimp1 element previously identified in the ascomycete fungus Fusarium
      oxysporum has hallmarks of miniature inverted-repeat transposable elements
      (MITEs): short size, terminal inverted repeats (TIRs), structural homogeneity,
      and a stable secondary structure. Since mimp1 has no coding capacity, its
      mobilization requires a transposase-encoding element. On the basis of the
      similarity of TIRs and target-site preference with the autonomous Tc1-like
      element impala, together with a correlated distribution of both elements among
      the Fusarium genus, we investigated the ability of mimp1 to jump upon expression
      of the impala transposase provided in trans. Under these conditions, we present
      evidence that mimp1 transposes by a cut-and-paste mechanism into TA
      dinucleotides, which are duplicated upon insertion. Our results also show that
      mimp1 reinserts very frequently in genic regions for at least one-third of the
      cases. We also show that the mimp1/impala double-component system is fully
      functional in the heterologous species F. graminearum, allowing the development
      of a highly efficient tool for gene tagging in filamentous fungi.

PMID- 17179072
TI  - Misexpression screen in Drosophila melanogaster aiming to reveal novel factors
      involved in formation of body parts.
AB  - To identify novel factors that lead a fly imaginal disc to adopt its
      developmental fate, we carried out a modular dominant misexpression screen in
      imaginal discs. We have identified two factors that appear to change the fate of
      the respective body structure and appear to lead to the transformation of a body
      part. In one mutant line, notum tissue, normally derived from wing imaginal
      tissue, formed close to the site of the sternopleural bristles, which are leg
      disc derivatives. In the other line, the arista is transformed into a tubular
      structure, resembling an abnormal leg. We found that ectopic expression of abrupt
      was responsible for this potential transformation of the arista.

PMID- 17179073
TI  - Opposite effects of tor1 and tor2 on nitrogen starvation responses in fission
      yeast.
AB  - The TOR protein kinases exhibit a conserved role in regulating cellular growth
      and proliferation. In the fission yeast two TOR homologs are present. tor1(+) is
      required for starvation and stress responses, while tor2(+) is essential. We
      report here that Tor2 depleted cells show a phenotype very similar to that of
      wild-type cells starved for nitrogen, including arrest at the G(1) phase of the
      cell cycle, induction of nitrogen-starvation-specific genes, and entrance into
      the sexual development pathway. The phenotype of tor2 mutants is in a striking
      contrast to the failure of tor1 mutants to initiate sexual development or arrest
      in G(1) under nitrogen starvation conditions. Tsc1 and Tsc2, the genes mutated in
      the human tuberous sclerosis complex syndrome, negatively regulate the mammalian
      TOR via inactivation of the GTPase Rheb. We analyzed the genetic relationship
      between the two TOR genes and the Schizosaccharomyces pombe orthologs of TSC1,
      TSC2, and Rheb. Our data suggest that like in higher eukaryotes, the Tsc1-2
      complex negatively regulates Tor2. In contrast, the Tsc1-2 complex and Tor1
      appear to work in parallel, both positively regulating amino acid uptake through
      the control of expression of amino acid permeases. Additionally, either Tsc1/2 or
      Tor1 are required for growth on a poor nitrogen source such as proline. Mutants
      lacking Tsc1 or Tsc2 are highly sensitive to rapamycin under poor nitrogen
      conditions, suggesting that the function of Tor1 under such conditions is
      sensitive to rapamycin. We discuss the complex genetic interactions between
      tor1(+), tor2(+), and tsc1/2(+) and the implications for rapamycin sensitivity in
      tsc1 or tsc2 mutants.

PMID- 17179075
TI  - Estimation of population heterozygosity and library construction-induced mutation
      rate from expressed sequence tag collections.
AB  - Unigene alignments obtained from cDNA libraries made using multiple individuals
      are not currently used to estimate population heterozygosity, as they are known
      to harbor mutations created during library construction. We describe an estimator
      of population heterozygosity that utilizes only SNPs unlikely to be library
      construction artifacts.

PMID- 17179074
TI  - The cloning and characterization of the histone acetyltransferase human homolog
      Dmel?TIP60 in Drosophila melanogaster: Dmel?TIP60 is essential for multicellular
      development.
AB  - Chromatin packaging directly influences gene programming as it permits only
      certain portions of the genome to be activated in any given developmental stage,
      cell, and tissue type. Histone acetyltransferases (HATs) are a key class of
      chromatin regulatory proteins that mediate such developmental chromatin control;
      however, their specific roles during multicellular development remain unclear.
      Here, we report the first isolation and developmental characterization of a
      Drosophila HAT gene (Dmel?TIP60) that is the homolog of the human HAT gene TIP60.
      We show that Dmel?TIP60 is differentially expressed during Drosophila
      development, with transcript levels significantly peaking during embryogenesis.
      We further demonstrate that reducing endogenous Dmel?TIP60 expression in
      Drosophila embryonic cells by RNAi results in cellular defects and lethality.
      Finally, using a GAL4-targeted RNAi system in Drosophila, we show that ubiquitous
      or mesoderm/muscle-specific reduction of Dmel?TIP60 expression results in
      lethality during fly development. Our results suggest a mechanism for HAT
      regulation involving developmental control of HAT expression profiles and show
      that Dmel?TIP60 is essential for multicellular development. Significantly, our
      inducible and targeted HAT knockdown system in Drosophila now provides a powerful
      tool for effectively studying the roles of TIP60 in specific tissues and cell
      types during development.

PMID- 17179076
TI  - Natural variation in the Pto disease resistance gene within species of wild
      tomato (Lycopersicon). II. Population genetics of Pto.
AB  - Disease resistance to the bacterial pathogen Pseudomonas syringae pv. tomato
      (Pst) in the host species Lycopersicon esculentum, the cultivated tomato, and the
      closely related L. pimpinellifolium is triggered by the physical interaction
      between the protein products of the host resistance (R) gene Pto and the pathogen
      avirulence genes AvrPto and AvrPtoB. Sequence variation at the Pto locus was
      surveyed in natural populations of seven species of Lycopersicon to test
      hypotheses of host-parasite coevolution and functional adaptation of the Pto
      gene. Pto shows significantly higher nonsynonymous polymorphism than 14 other non
      R-gene loci in the same samples of Lycopersicon species, while showing no
      difference in synonymous polymorphism, suggesting that the maintenance of amino
      acid polymorphism at this locus is mediated by pathogen selection. Also, a larger
      proportion of ancestral variation is maintained at Pto as compared to these non-R
      gene loci. The frequency spectrum of amino acid polymorphisms known to negatively
      affect Pto function is skewed toward low frequency compared to amino acid
      polymorphisms that do not affect function or silent polymorphisms. Therefore, the
      evolution of Pto appears to be influenced by a mixture of both purifying and
      balancing selection.

PMID- 17179077
TI  - Identifying quantitative trait locus by genetic background interactions in
      association studies.
AB  - Association studies are designed to identify main effects of alleles across a
      potentially wide range of genetic backgrounds. To control for spurious
      associations, effects of the genetic background itself are often incorporated
      into the linear model, either in the form of subpopulation effects in the case of
      structure or in the form of genetic relationship matrices in the case of complex
      pedigrees. In this context epistatic interactions between loci can be captured as
      an interaction effect between the associated locus and the genetic background. In
      this study I developed genetic and statistical models to tie the locus by genetic
      background interaction idea back to more standard concepts of epistasis when
      genetic background is modeled using an additive relationship matrix. I also
      simulated epistatic interactions in four-generation randomly mating pedigrees and
      evaluated the ability of the statistical models to identify when a biallelic
      associated locus was epistatic to other loci. Under additive-by-additive
      epistasis, when interaction effects of the associated locus were quite large
      (explaining 20% of the phenotypic variance), epistasis was detected in 79% of
      pedigrees containing 320 individuals. The epistatic model also predicted the
      genotypic value of progeny better than a standard additive model in 78% of
      simulations. When interaction effects were smaller (although still fairly large,
      explaining 5% of the phenotypic variance), epistasis was detected in only 9% of
      pedigrees containing 320 individuals and the epistatic and additive models were
      equally effective at predicting the genotypic values of progeny. Epistasis was
      detected with the same power whether the overall epistatic effect was the result
      of a single pairwise interaction or the sum of nine pairwise interactions, each
      generating one ninth of the epistatic variance. The power to detect epistasis was
      highest (94%) at low QTL minor allele frequency, fell to a minimum (60%) at minor
      allele frequency of about 0.2, and then plateaued at about 80% as alleles reached
      intermediate frequencies. The power to detect epistasis declined when the linkage
      disequilibrium between the DNA marker and the functional polymorphism was not
      complete.

PMID- 17179078
TI  - G72/G30 genes and schizophrenia: a systematic meta-analysis of association
      studies.
AB  - Schizophrenia may result from a neurotransmission hypofunction of glutamatergic
      and N-methyl-d-aspartate (NMDA) receptors. Linkage disequilibrium mapping has
      identified several promising and novel positional candidates, including the
      G72/G30 and d-amino-acid oxidase (DAAO) genes. Since the first positive
      association report, many subsequent studies have attempted to replicate the
      association but the results have been mixed. To try to resolve this inconsistency
      and to elucidate the relationship between the important glutamate-related genes
      and schizophrenia, the current meta-analysis has combined samples involving 16
      polymorphisms covering all published case-control and family-based association
      studies up to October 2005. The results suggest that there is weak evidence of
      association between the G72/G30 genes and schizophrenia.

PMID- 17179079
TI  - A microsatellite linkage map of Barramundi, Lates calcarifer.
AB  - Barramundi (Lates calcarifer) is an important farmed marine food fish species.
      Its compact genome (approximately 700 Mb) is among the smallest genomes of food
      fish species. We established a first-generation genetic linkage map of Barramundi
      with a mapping panel containing three parents (two males and one female) and 93
      progeny. A total of 240 microsatellite markers were mapped into 24 linkage
      groups. Among these markers, 10 were located in ESTs and known genes. The total
      lengths of the female and male maps were 873.8 and 414.5 cM with an average
      marker spacing of 6.20 and 4.70 cM, respectively. Comparing the flanking
      sequences of the 240 Barramundi microsatellites with the assembled whole-genome
      sequences of Tetraodon nigrovidiris revealed 55 homologous sequences located in
      19 of the 21 chromosomes of T. nigrovidiris. The map will not only enable the
      mapping of quantitative trait loci, but also provide new resources for
      understanding the evolution of fish genomes.

PMID- 17179080
TI  - Evolutionary conservation of the FLOWERING LOCUS C-mediated vernalization
      response: evidence from the sugar beet (Beta vulgaris).
AB  - In many plant species, exposure to a prolonged period of cold during the winter
      promotes flowering in the spring, a process termed vernalization. In Arabidopsis
      thaliana, the vernalization requirement of winter-annual ecotypes is caused by
      the MADS-box gene FLOWERING LOCUS C (FLC), which is a repressor of flowering.
      During the vernalization process, FLC is downregulated by alteration of its
      chromatin structure, thereby permitting flowering to occur. In wheat, a
      vernalization requirement is imposed by a different repressor of flowering,
      suggesting that some components of the regulatory network controlling the
      vernalization response differ between monocots and dicots. The extent to which
      the molecular mechanisms underlying vernalization have been conserved during the
      diversification of the angiosperms is not well understood. Using phylogenetic
      analysis, we identified homologs of FLC in species representing the three major
      eudicot lineages. FLC homologs have not previously been documented outside the
      plant family Brassicaceae. We show that the sugar beet FLC homolog BvFL1
      functions as a repressor of flowering in transgenic Arabidopsis and is
      downregulated in response to cold in sugar beet. Cold-induced downregulation of
      an FLC-like floral repressor may be a central feature of the vernalization
      response in at least half of eudicot species.

PMID- 17179081
TI  - Genetic evidence for a SPO1-dependent signaling pathway controlling meiotic
      progression in yeast.
AB  - The yeast spindle pole body (SPB) plays a unique role in meiosis, initiating both
      spindle assembly and prospore membrane synthesis. SPO1, induced early in
      development, encodes a meiosis-specific phospholipase B (PLB) homolog required at
      three stages of SPB morphogenesis: MI, MII, and spore formation. Here we report
      in-depth analysis of the SPO1 gene including its transcriptional control by
      regulators of early gene expression, protein localization to the ER lumen and
      periplasmic space, and molecular genetic studies of its role in meiosis. Evidence
      is presented that multiple arrest points in spo1Delta occur independently,
      demonstrating that Spo1 acts at distinct steps. Loss of Spo1 is suppressed by
      high-copy glycosylphosphatidylinositol (GPI) proteins, dependent on sequence,
      timing, and strength of induction in meiosis. Since phosphatidylinositol (PI)
      serves as both an anchor component and a lipase substrate, we hypothesized that
      GPI-protein expression might substitute for Spo1 by decreasing levels of its
      potential substrates, PI and phosphatidylinositol phosphates (PIPs). Partial
      spo1Delta complementation by PLB3 (encoding a unique PLB capable of cleaving PI)
      and relatively strong Spo1 binding to PI(4)P derivatives (via a novel N-terminal
      lysine-rich fragment essential for Spo1 function) are consistent with this view.
      Epistasis of SPO1 mutations to those in SPO14 (encoding a PLD involved in
      signaling) and physical interaction of Spo1 with Spo23, a protein regulating PI
      synthesis required for wild-type sporulation, further support this notion. Taken
      together these findings implicate PI and/or PIPs in Spo1 function and suggest the
      existence of a novel Spo1-dependent meiosis-specific signaling pathway required
      for progression of MI, MII, and spore formation via regulation of the SPB.

PMID- 17179082
TI  - Identification of genes that interact with Drosophila liquid facets.
AB  - We have performed mutagenesis screens of the Drosophila X chromosome and the
      autosomes for dominant enhancers of the rough eye resulting from overexpression
      of liquid facets. The liquid facets gene encodes the homolog of vertebrate
      endocytic Epsin, an endocytic adapter protein. In Drosophila, Liquid facets is a
      core component of the Notch signaling pathway required in the signaling cells for
      ligand endocytosis and signaling. Why ligand internalization by the signaling
      cells is essential for signaling is a mystery. The requirement for Liquid facets
      is a hint at the answer, and the genes identified in this screen provide further
      clues. Mutant alleles of clathrin heavy chain, Rala, split ends, and auxilin were
      identified as enhancers. We describe the mutant alleles and mutant phenotypes of
      Rala and aux. We discuss the relevance of all of these genetic interactions to
      the function of Liquid facets in Notch signaling.

PMID- 17179083
TI  - Histone H3 lysine 36 methylation antagonizes silencing in Saccharomyces
      cerevisiae independently of the Rpd3S histone deacetylase complex.
AB  - In yeast, methylation of histone H3 on lysine 36 (H3-K36) is catalyzed by the
      NSD1 leukemia oncoprotein homolog Set2. The histone deacetylase complex Rpd3S is
      recruited to chromatin via binding of the chromodomain protein Eaf3 to methylated
      H3-K36 to prevent erroneous transcription initiation. Here we identify a distinct
      function for H3-K36 methylation. We used random mutagenesis of histones H3 and H4
      followed by a reporter-based screen to identify residues necessary to prevent the
      ectopic spread of silencing from the silent mating-type locus HMRa into flanking
      euchromatin. Mutations in H3-K36 or deletion of SET2 caused ectopic silencing of
      a heterochromatin-adjacent reporter. Transcriptional profiling revealed that
      telomere-proximal genes are enriched for those that display decreased expression
      in a set2Delta strain. Deletion of SIR4 rescued the expression defect of 26 of 37
      telomere-proximal genes with reduced expression in set2Delta cells, implying that
      H3-K36 methylation prevents the spread of telomeric silencing. Indeed, Sir3
      spreads from heterochromatin into neighboring euchromatin in set2Delta cells.
      Furthermore, genetic experiments demonstrated that cells lacking the Rpd3S
      specific subunits Eaf3 or Rco1 did not display the anti-silencing phenotype of
      mutations in SET2 or H3-K36. Thus, antagonism of silencing is independent of the
      only known effector of this conserved histone modification.

PMID- 17179085
TI  - Deterministic and stochastic regimes of asexual evolution on rugged fitness
      landscapes.
AB  - We study the adaptation dynamics of an initially maladapted asexual population
      with genotypes represented by binary sequences of length L. The population
      evolves in a maximally rugged fitness landscape with a large number of local
      optima. We find that whether the evolutionary trajectory is deterministic or
      stochastic depends on the effective mutational distance d(eff) up to which the
      population can spread in genotype space. For d(eff) = L, the deterministic quasi
      species theory operates while for d(eff) < 1, the evolution is completely
      stochastic. Between these two limiting cases, the dynamics are described by a
      local quasi-species theory below a crossover time T(x) while above T(x) the
      population gets trapped at a local fitness peak and manages to find a better peak
      via either stochastic tunneling or double mutations. In the stochastic regime
      d(eff) < 1, we identify two subregimes associated with clonal interference and
      uphill adaptive walks, respectively. We argue that our findings are relevant to
      the interpretation of evolution experiments with microbial populations.

PMID- 17179084
TI  - A genetic screen for modifiers of the delta1-dependent notch signaling function
      in the mouse.
AB  - The Notch signaling pathway is an evolutionarily conserved transduction pathway
      involved in embryonic patterning and regulation of cell fates during development.
      Recent studies have demonstrated that this pathway is integral to a complex
      system of interactions, which are also involved in distinct human diseases.
      Delta1 is one of the known ligands of the Notch receptors. Mice homozygous for a
      loss-of-function allele of the Delta1 gene Dll1(lacZ/lacZ) die during embryonic
      development. Here, we present the results of two phenotype-driven modifier
      screens. Heterozygous Dll1(lacZ) knockout animals were crossed with ENU
      mutagenized mice and screened for dysmorphological, clinical chemical, and
      immunological variants that are dependent on the Delta1 loss-of-function allele.
      First, we show that mutagenized heterozygous Dll1(lacZ) offspring have reduced
      body weight and altered specific clinical chemical parameters, including changes
      in metabolites and electrolytes relevant for kidney function. In our mutagenesis
      screen we have successfully generated 35 new mutant lines. Of major interest are
      7 mutant lines that exhibit a Dll1(lacZ/+)-dependent phenotype. These mutant
      mouse lines provide excellent in vivo tools for studying the role of Notch
      signaling in kidney and liver function, cholesterol and iron metabolism, cell
      fate decisions, and during maturation of T cells in the immune system.

PMID- 17179086
TI  - Inheritance of gynandromorphism in the parasitic wasp Nasonia vitripennis.
AB  - The parasitic wasp Nasonia vitripennis has haplo-diploid sex determination. Males
      develop from unfertilized eggs and are haploid, whereas females develop from
      fertilized eggs and are diploid. Females and males can be easily distinguished by
      their morphology. A strain that produces individuals with both male and female
      features (gynandromorphs) is studied. We provide data on female/male patterning
      within and between individuals, on environmental effects influencing the
      occurrence of gynandromorphism, and on its pattern of inheritance. A clear
      anterior/posterior pattern of feminization is evident in gynandromorphic
      individuals that developed from unfertilized haploid eggs. The proportion of
      gynandromorphic individuals can be increased by exposing the mothers to high
      temperature and also by exposing embryos at early stages of development.
      Selection for increased gynandromorph frequency was successful. Backcross and
      introgression experiments showed that a combination of a nuclear and a heritable
      cytoplasmic component causes gynandromorphism. Analyses of reciprocal F(2) and
      F(3) progeny indicate a maternal effect locus (gyn1) that maps to chromosome IV.
      Coupled with previous studies, our results are consistent with a N. vitripennis
      sex determination involving a maternal/zygotic balance system and/or maternal
      imprinting. Genetics and temperature effects suggest a temperature-sensitive
      mutation of a maternally produced masculinizing product that acts during a
      critical period in early embryogenesis.

PMID- 17179087
TI  - The alternative pathway of glutathione degradation is mediated by a novel protein
      complex involving three new genes in Saccharomyces cerevisiae.
AB  - Glutathione (GSH), L-gamma-glutamyl-L-cysteinyl-glycine, is the major low
      molecular-weight thiol compound present in almost all eukaryotic cells. GSH
      degradation proceeds through the gamma-glutamyl cycle that is initiated, in all
      organisms, by the action of gamma-glutamyl transpeptidase. A novel pathway for
      the degradation of GSH that requires the participation of three previously
      uncharacterized genes is described in the yeast Saccharomyces cerevisiae. These
      genes have been named DUG1 (YFR044c), DUG2 (YBR281c), and DUG3 (YNL191w)
      (defective in utilization of glutathione). Although dipeptides and tripeptides
      with a normal peptide bond such as cys-gly or glu-cys-gly required the presence
      of only a functional DUG1 gene that encoded a protein belonging to the M20A
      metallohydrolase family, the presence of an unusual peptide bond such as in the
      dipeptide, gamma-glu-cys, or in GSH, required the participation of the DUG2 and
      DUG3 gene products as well. The DUG2 gene encodes a protein with a peptidase
      domain and a large WD40 repeat region, while the DUG3 gene encoded a protein with
      a glutamine amidotransferase domain. The Dug1p, Dug2p, and Dug3p proteins were
      found to form a degradosomal complex through Dug1p-Dug2p and Dug2p-Dug3p
      interactions. A model is proposed for the functioning of the Dug1p/Dug2p/Dug3p
      proteins as a specific GSH degradosomal complex.

PMID- 17179089
TI  - Development of a near-isogenic line population of Arabidopsis thaliana and
      comparison of mapping power with a recombinant inbred line population.
AB  - In Arabidopsis recombinant inbred line (RIL) populations are widely used for
      quantitative trait locus (QTL) analyses. However, mapping analyses with this type
      of population can be limited because of the masking effects of major QTL and
      epistatic interactions of multiple QTL. An alternative type of immortal
      experimental population commonly used in plant species are sets of introgression
      lines. Here we introduce the development of a genomewide coverage near-isogenic
      line (NIL) population of Arabidopsis thaliana, by introgressing genomic regions
      from the Cape Verde Islands (Cvi) accession into the Landsberg erecta (Ler)
      genetic background. We have empirically compared the QTL mapping power of this
      new population with an already existing RIL population derived from the same
      parents. For that, we analyzed and mapped QTL affecting six developmental traits
      with different heritability. Overall, in the NIL population smaller-effect QTL
      than in the RIL population could be detected although the localization resolution
      was lower. Furthermore, we estimated the effect of population size and of the
      number of replicates on the detection power of QTL affecting the developmental
      traits. In general, population size is more important than the number of
      replicates to increase the mapping power of RILs, whereas for NILs several
      replicates are absolutely required. These analyses are expected to facilitate
      experimental design for QTL mapping using these two common types of segregating
      populations.

PMID- 17179088
TI  - Cis-regulatory elements in the Accord retrotransposon result in tissue-specific
      expression of the Drosophila melanogaster insecticide resistance gene Cyp6g1.
AB  - Transposable elements are a major mutation source and powerful agents of adaptive
      change. Some transposable element insertions in genomes increase to a high
      frequency because of the selective advantage the mutant phenotype provides.
      Cyp6g1-mediated insecticide resistance in Drosophila melanogaster is due to the
      upregulation of the cytochrome P450 gene Cyp6g1, leading to the resistance to a
      variety of insecticide classes. The upregulation of Cyp6g1 is correlated with the
      presence of the long terminal repeat (LTR) of an Accord retrotransposon inserted
      291bp upstream of the Cyp6g1 transcription start site. This resistant allele (DDT
      R) is currently at a high frequency in D. melanogaster populations around the
      world. Here, we characterize the spatial expression of Cyp6g1 in insecticide
      resistant and -susceptible strains. We show that the Accord LTR insertion is
      indeed the resistance-associated mutation and demonstrate that the Accord LTR
      carries regulatory sequences that increase the expression of Cyp6g1 in tissues
      important for detoxification, the midgut, Malpighian tubules, and the fat body.
      This study provides a significant example of how changes in tissue-specific gene
      expression caused by transposable-element insertions can contribute to
      adaptation.

PMID- 17179090
TI  - Mammalian mRNA splice-isoform selection is tightly controlled.
AB  - Post-transcriptional RNA processing is an important regulatory control mechanism
      for determining the phenotype of eukaryotic cells. The processing of a
      transcribed RNA species into alternative splice isoforms yields products that can
      perform different functions. Each type of cell in a multi-cellular organism is
      presumed to actively control the relative quantities of alternative splice
      isoforms. In this study, the alternatively spliced isoforms of five mRNA
      transcription units were examined by quantitative reverse transcription-PCR
      amplification. We show that interindividual variation in splice-isoform selection
      is very highly constrained when measured in a large population of genetically
      diverse mice (i.e., full siblings; N = 150). Remarkably, splice-isoform ratios
      are among the most invariant phenotypes measured in this population and are
      confirmed in a second, genetically distinct population. In addition, the patterns
      of splice-isoform selection show tissue-specific and age-related changes. We
      propose that splice-isoform selection is exceptionally robust to genetic and
      environmental variability and may provide a control point for cellular
      homeostasis. As a consequence, splice-isoform ratios may be useful as a practical
      quantitative measure of the physiological status of cells and tissues.

PMID- 17179091
TI  - Epigenetic modifications of distinct sequences of the p1 regulatory gene specify
      tissue-specific expression patterns in maize.
AB  - Tandemly repeated endogenous genes are common in plants, but their
      transcriptional regulation is not well characterized. In maize, the P1-wr allele
      of pericarp color1 is composed of multiple copies arranged in a head-to-tail
      fashion. P1-wr confers a white kernel pericarp and red cob glume pigment
      phenotype that is stably inherited over generations. To understand the molecular
      mechanisms that regulate tissue-specific expression of P1-wr, we have
      characterized P1-wr*, a spontaneous loss-of-function epimutation that shows a
      white kernel pericarp and white cob glume phenotype. As compared to its
      progenitor P1-wr, the P1-wr* is hypermethylated in exon 1 and intron 2 regions.
      In the presence of the epigenetic modifier Ufo1 (Unstable factor for orange1), P1
      wr* plants exhibit a range of cob glume pigmentation whereas pericarps remain
      colorless. In these plants, the level of cob pigmentation directly correlates
      with the degree of DNA demethylation in the intron 2 region of p1. Further,
      genomic bisulfite sequencing indicates that a 168-bp region of intron 2 is
      significantly hypomethylated in both CG and CNG context in P1-wr* Ufo1 plants.
      Interestingly, P1-wr* Ufo1 plants did not show any methylation change in a distal
      enhancer region that has previously been implicated in Ufo1-induced gain of
      pericarp pigmentation of the P1-wr allele. These results suggest that distinct
      regulatory sequences in the P1-wr promoter and intron 2 regions can undergo
      independent epigenetic modifications to generate tissue-specific expression
      patterns.

PMID- 17179092
TI  - Functional deficiency in IL-7 caused by an N-ethyl-N-nitrosourea-induced point
      mutation.
AB  - N-ethyl-N-nitrosourea (ENU)-induced mutagenesis provides a powerful approach for
      identifying genes involved in immune regulation and diseases. Here we describe a
      new mutant strain, HLB368, with hereditary leukopenia. At necropsy, the mutant
      mice had very small thymuses and spleens. All but the inguinal nodes were absent
      and there were no Peyer's patches. By flow cytometry, the ratios of T-cell
      subsets were normal, but B-cell development was blocked at the pre-pro-B-cell
      stage. The development of B1 and marginal zone B cells was relatively normal. The
      mutation was mapped to chromosome 3 between D3Mit221 and D3Mit224, a region that
      contains the Il7 gene. cDNA and genomic DNA sequences of Il7 revealed a T-to-C
      missense transition resulting in a change of Leu to Pro within the leader peptide
      that would be predicted to inhibit secretion. In keeping with this concept, we
      found that in vitro treatment of B-cell progenitors from mutant mice with IL-7
      induced them to differentiate into pre-BII cells. Phenotypic comparisons of
      HLB368 with genetically targeted Il7 null mice showed many similarities along
      with a few differences, indicating that this ENU-induced mutant carries a novel
      allele. This new strain thus provides a new model for studying the functions of
      IL-7 on a pure C57BL/6 background.

PMID- 17179093
TI  - Genes required for osmoregulation and apical secretion in Caenorhabditis elegans.
AB  - Few studies have investigated whether or not there is an interdependence between
      osmoregulation and vesicular trafficking. We previously showed that in
      Caenorhabditis elegans che-14 mutations affect osmoregulation, cuticle secretion,
      and sensory organ development. We report the identification of seven lethal
      mutations displaying che-14-like phenotypes, which define four new genes, rdy-1
      rdy-4 (rod-like larval lethality and dye-filling defective). rdy-1, rdy-2, and
      rdy-4 mutations affect excretory canal function and cuticle formation. Moreover,
      rdy-1 and rdy-2 mutations reduce the amount of matrix material normally secreted
      by sheath cells in the amphid channel. In contrast, rdy-3 mutants have short
      cystic excretory canals, suggesting that it acts in a different process. rdy-1
      encodes the vacuolar H+-ATPase a-subunit VHA-5, whereas rdy-2 encodes a new
      tetraspan protein. We suggest that RDY-1/VHA-5 acts upstream of RDY-2 and CHE-14
      in some tissues, since it is required for their delivery to the epidermal, but
      not the amphid sheath, apical plasma membrane. Hence, the RDY-1/VHA-5 trafficking
      function appears essential in some cells and its proton pump function essential
      in others. Finally, we show that RDY-1/VHA-5 distribution changes prior to
      molting in parallel with that of actin microfilaments and propose a model for
      molting whereby actin provides a spatial cue for secretion.

PMID- 17179094
TI  - Exploring strategies for protein trapping in Drosophila.
AB  - The use of fluorescent protein tags has had a huge impact on cell biological
      studies in virtually every experimental system. Incorporation of coding sequence
      for fluorescent proteins such as green fluorescent protein (GFP) into genes at
      their endogenous chromosomal position is especially useful for generating GFP
      fusion proteins that provide accurate cellular and subcellular expression data.
      We tested modifications of a transposon-based protein trap screening procedure in
      Drosophila to optimize the rate of recovering useful protein traps and their
      analysis. Transposons carrying the GFP-coding sequence flanked by splice acceptor
      and donor sequences were mobilized, and new insertions that resulted in
      production of GFP were captured using an automated embryo sorter. Individual
      stocks were established, GFP expression was analyzed during oogenesis, and
      insertion sites were determined by sequencing genomic DNA flanking the
      insertions. The resulting collection includes lines with protein traps in which
      GFP was spliced into mRNAs and embedded within endogenous proteins or enhancer
      traps in which GFP expression depended on splicing into transposon-derived RNA.
      We report a total of 335 genes associated with protein or enhancer traps and a
      web-accessible database for viewing molecular information and expression data for
      these genes.

PMID- 17179095
TI  - Contribution of Trf4/5 and the nuclear exosome to genome stability through
      regulation of histone mRNA levels in Saccharomyces cerevisiae.
AB  - Balanced levels of histones are crucial for chromosome stability, and one major
      component of this control regulates histone mRNA amounts. The Saccharomyces
      cerevisiae poly(A) polymerases Trf4 and Trf5 are involved in a quality control
      mechanism that mediates polyadenylation and consequent degradation of various RNA
      species by the nuclear exosome. None of the known RNA targets, however, explains
      the fact that trf mutants have specific cell cycle defects consistent with a role
      in maintaining genome stability. Here, we investigate the role of Trf4/5 in
      regulation of histone mRNA levels. We show that loss of Trf4 and Trf5, or of
      Rrp6, a component of the nuclear exosome, results in elevated levels of
      transcripts encoding DNA replication-dependent histones. Suggesting that
      increased histone levels account for the phenotypes of trf mutants, we find that
      TRF4 shows synthetic genetic interactions with genes that negatively regulate
      histone levels, including RAD53. Moreover, synthetic lethality of trf4Delta
      rad53Delta is rescued by reducing histone levels whereas overproduction of
      histones is deleterious to trf's and rrp6Delta mutants. These results identify
      TRF4, TRF5, and RRP6 as new players in the regulation of histone mRNA levels in
      yeast. To our knowledge, the histone transcripts are the first mRNAs that are
      upregulated in Trf mutants.

PMID- 17179096
TI  - In vivo construction of transgenes in Drosophila.
AB  - Transgenic flies are generated by transposon-mediated transformation. A drawback
      of this approach is the size limit of transposable elements. Here, we propose a
      novel method that allows the extension of transgenes in vivo. This method is
      based on an incomplete transgene that has been constructed in vitro and
      integrated into the Drosophila genome by conventional transgenesis. The
      incomplete transgene contains two short stretches of DNA homologous to the 5'-
      and 3'-ends of a larger DNA segment of interest. Between the short stretches of
      homology an I-SceI recognition site is located. Once activated, I-SceI
      endonuclease introduces a DNA double-strand break, which triggers ectopic
      recombination between the stretches of homology and the endogenous locus. Through
      gap repair, the transgene obtains the complete region of interest in vivo. Our
      results show that this method is effective for copying up to 28 kb of genomic DNA
      into the transgene, thereby eliminating the technical difficulties associated
      with the in vitro construction of large transgenes and extending the size limits
      of current transgenesis protocols. In general, this method may be a useful
      technique for genetic engineering of eukaryotic model organisms.

PMID- 17179097
TI  - Global eQTL mapping reveals the complex genetic architecture of transcript-level
      variation in Arabidopsis.
AB  - The genetic architecture of transcript-level variation is largely unknown. The
      genetic determinants of transcript-level variation were characterized in a
      recombinant inbred line (RIL) population (n = 211) of Arabidopsis thaliana using
      whole-genome microarray analysis and expression quantitative trait loci (eQTL)
      mapping of transcript levels as expression traits (e-traits). Genetic control of
      transcription was highly complex: one-third of the quantitatively controlled
      transcripts/e-traits were regulated by cis-eQTL, and many trans-eQTL mapped to
      hotspots that regulated hundreds to thousands of e-traits. Several thousand eQTL
      of large phenotypic effect were detected, but almost all (93%) of the 36,871 eQTL
      were associated with small phenotypic effects (R(2) < 0.3). Many transcripts/e
      traits were controlled by multiple eQTL with opposite allelic effects and
      exhibited higher heritability in the RILs than their parents, suggesting
      nonadditive genetic variation. To our knowledge, this is the first large-scale
      global eQTL study in a relatively large plant mapping population. It reveals that
      the genetic control of transcript level is highly variable and multifaceted and
      that this complexity may be a general characteristic of eukaryotes.

PMID- 17179098
TI  - Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin,
      and fluorouracil for patients with advanced or recurrent breast cancer.
AB  - PURPOSE: To evaluate the efficacy and tolerability of dofequidar plus
      cyclophosphamide, doxorubicin, and fluorouracil (CAF) therapy in comparison with
      CAF alone, in patients with advanced or recurrent breast cancer. Dofequidar is a
      novel, orally active quinoline derivative that reverses multidrug resistance.
      PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled trial,
      patients were treated with six cycles of CAF therapy: 28 days/cycle, with
      doxorubicin (25 mg/m2) and fluorouracil (500 mg/m2) administered on days 1 and 8
      and cyclophosphamide (100 mg orally [PO]) administered on day 1 through 14.
      Patients received dofequidar (900 mg PO) 30 minutes before each dose of
      doxorubicin. Primary end point was overall response rate (ORR; partial or
      complete response). In total, 221 patients were assessable. RESULTS: ORR was
      42.6% for CAF compared with 53.1% for dofequidar + CAF, a 24.6% relative
      improvement and 10.5% absolute increase (P = .077). There was a trend for
      prolonged progression-free survival (PFS; median 241 days for CAF v 366 days for
      dofequidar + CAF; P = .145). In retrospectively defined subgroups, significant
      improvement in PFS in favor of dofequidar was observed in patients who were
      premenopausal, had no prior therapy, and were stage IV at diagnosis with an
      intact primary tumor. Except for neutropenia and leukopenia, there was no
      statistically significant excess of grade 3/4 adverse events compared with CAF.
      Treatment with dofequidar did not affect the plasma concentration of doxorubicin.
      CONCLUSION: Dofequidar + CAF was well tolerated and is suggested to have efficacy
      in patients who had not received prior therapy.

PMID- 17179099
TI  - Human papillomavirus and prognosis of oropharyngeal squamous cell carcinoma:
      implications for clinical research in head and neck cancers.

PMID- 17179100
TI  - ASCO core values: essential to progress in innovative, quality cancer care.

PMID- 17179101
TI  - High-risk human papillomavirus affects prognosis in patients with surgically
      treated oropharyngeal squamous cell carcinoma.
AB  - PURPOSE: Human papillomavirus (HPV) DNA tumors actively integrating the E6 and E7
      oncogenes have a distinct biologic behavior resulting in a more favorable
      prognosis. To which extent the viral integration by itself, and/or the associated
      wild-type (wt) TP53 status, and/or a functional p16 contribute to prognosis is
      unclear. PATIENTS AND METHODS: To clarify how the presence of high-risk (HR) 
      HPV, TP53, and p16INK4a status interact with clinical outcome, we considered a
      retrospective series of 90 consecutive oropharyngeal cancer patients treated
      primarily with surgery. RESULTS: Seventeen (19%) patients showed integrated HPV
      16 DNA (HPV positive), wt TP53 in all but two patients, normal p16INK4a in 15
      assessable patients, and p16 expression in all 17 patients. Thirty-five patients
      (39%), two of whom were HPV positive, harbored TP53 mutations. p16INK4a deletion
      and p16 null immunophenotype occurred in 28 and 58 patients, respectively, and
      was similarly distributed in both patients with mutated TP53 (48% and 82%,
      respectively) and in patients with wt TP53 (46% and 77%, respectively).
      Statistical analysis showed that HPV-positive status significantly affects all
      investigated end points: overall survival (P = .0018), incidence of tumor relapse
      (P = .0371), and second tumor (P = .0152), whereas TP53 and p16INK4a status and
      p16 expression were not prognostic by themselves. CONCLUSION: Our molecular and
      clinical results are in agreement with previous findings but provide additional
      information into the biologic mechanisms involved in HR-HPV oropharyngeal cancer
      in comparison to HPV-negative tumors. According to the reduced risk of relapse
      and second tumors associated with HR-HPV positivity of oropharyngeal cancer, the
      therapeutic strategy and follow-up procedures should be reviewed.

PMID- 17179102
TI  - Raf kinase inhibitor protein expression in a survival analysis of colorectal
      cancer patients.
AB  - PURPOSE: Raf kinase inhibitor protein (RKIP) inhibits the Raf and nuclear factor
      kappa B signaling pathways, and suppresses metastasis in animal models. We
      examined whether RKIP expression in primary colorectal cancers (CRCs) correlates
      with the risk of metastasis and overall survival. PATIENTS AND METHODS: RKIP
      expression was examined immunohistochemically in three separate cohorts: a tissue
      microarray containing 276 samples from human tumors and normal tissues, and
      retrospective studies of 268 CRC patients and 65 early-stage CRCs. Overall and
      metastasis-free survival rates were measured. RESULTS: RKIP was expressed in
      normal epithelia but was reduced in metastatic tumors. RKIP expression in primary
      CRC was an independent prognostic marker for survival using multivariate Cox
      regression analysis (hazard ratio, 2.808; 95% CI, 1.58 to 4.96; P = .0002),
      independent of Dukes' stage. Patients with Dukes' C RKIP-positive tumors had
      similar 5-year survival rates as early-stage patients if tumors had equivalent
      RKIP expression levels. An independent study of early-stage CRCs confirmed that
      reduced RKIP expression predicted metastatic recurrence and reduced disease-free
      survival (hazard ratio, 4.5; 95% CI, 1.7 to 12.3; P = .003). RKIP expression was
      independent of sex, age, mitotic index, lymphatic and vascular invasion, depth of
      invasion, and tumor site, but correlated positively with apoptotic index (P =
      .024). Weak or loss of RKIP expression was the most significant and independent
      prognostic marker using a multivariate regression equation (hazard ratio, 4.5;
      95% CI, 1.7 to 12.3; P = .003). CONCLUSION: RKIP expression in primary CRCs
      correlates with overall and disease-free survival, and can be useful for
      identifying early-stage CRC patients at risk of relapse.

PMID- 17179103
TI  - Hormone replacement therapy and survival after colorectal cancer diagnosis.
AB  - PURPOSE: Postmenopausal estrogen use has been shown to decrease the incidence of
      colorectal cancer, but there is limited information regarding the effect of
      estrogen use on survival after diagnosis of colorectal cancer. PARTICIPANTS AND
      METHODS: We examined the influence of postmenopausal estrogen use on mortality
      among 834 women participating in the Nurses' Health Study who were diagnosed with
      colorectal cancer between 1976 and 2000 and observed until death or June 2004,
      whichever came first. Colorectal cancer-specific mortality and overall mortality
      according to categories of hormone use were assessed. Cox proportional hazards
      models were used to calculate hazard ratios (HRs) adjusted for other risk factors
      for cancer survival. RESULTS: Postmenopausal estrogen use before diagnosis of
      colorectal cancer was associated with significant reduction in mortality.
      Compared with women with no prior estrogen use, those reporting current use
      before diagnosis had an adjusted HR of 0.64 (95% CI, 0.47 to 0.88) for colorectal
      cancer-specific mortality and 0.74 (95% CI, 0.56 to 0.97) for overall mortality.
      This inverse association between hormone use and mortality was most evident among
      women whose duration of use was less than 5 years. Longer durations and past use
      were not associated with significant survival benefit. Assessment of estrogen use
      after diagnosis demonstrated similar findings. CONCLUSION: Current postmenopausal
      estrogen use before diagnosis of colorectal cancer was associated with improved
      colorectal cancer-specific and overall mortality. This benefit was principally
      limited to women who initiated estrogens within 5 years of diagnosis. Additional
      efforts to understand mechanisms through which estrogens influence colorectal
      carcinogenesis and cancer progression seem warranted.

PMID- 17179104
TI  - Early invasive cervical cancer: tumor delineation by magnetic resonance imaging,
      computed tomography, and clinical examination, verified by pathologic results, in
      the ACRIN 6651/GOG 183 Intergroup Study.
AB  - PURPOSE: To compare magnetic resonance imaging (MRI), computed tomography (CT),
      and clinical examination for delineating early cervical cancer and for measuring
      tumor size. PATIENTS AND METHODS: A 25-center study enrolled 208 patients with
      biopsy-proven invasive cervical cancer for MRI and CT before attempted curative
      radical hysterectomy. Each imaging study was interpreted prospectively by one
      onsite radiologist and retrospectively by four independent offsite radiologists,
      who were all blinded to surgical, histopathologic, and other imaging findings.
      Likelihood of cervical stromal and uterine body involvement was rated on a 5
      point scale. Tumor size measurements were attempted in three axes. Surgical
      pathology was the standard of reference. RESULTS: Neither MRI nor CT was accurate
      for evaluating cervical stroma. For uterine body involvement, the area under the
      receiver operating characteristic curve was higher for MRI than for CT for both
      prospective (0.80 v 0.66, respectively; P = .01) and retrospective (0.68 v 0.57,
      respectively; P = .02) readings. Retrospective readers could measure diameter by
      CT in 35% to 73% of patients and by MRI in 79% to 94% of patients. Prospective
      readers had the highest Spearman correlation coefficient with pathologic
      measurement for MRI (r(s) = 0.54), followed by CT (r(s) = 0.45) and clinical
      examination (r(s) = 0.37; P < .0001 for all). Spearman correlation of
      multiobserver diameter measurements for MRI (r(s) = 0.58; P < .0001) was double
      that for CT (r(s) = 0.27; P = .03). CONCLUSION: In patients with cervical cancer,
      MRI is superior to CT and clinical examination for evaluating uterine body
      involvement and measuring tumor size, but no method was accurate for evaluating
      cervical stroma.

PMID- 17179106
TI  - Immunosurveillance and survivin-specific T-cell immunity in children with high
      risk neuroblastoma.
AB  - PURPOSE: Tumor immunosurveillance influences oncogenesis and tumor growth, but it
      remains controversial whether clinical failure of immunosurveillance is a result
      of lymphocyte dysfunction or tumor escape. In this study, our goal was to
      characterize the physiology of tumor immunosurveillance in children with high
      risk neuroblastoma (HR-NBL). PATIENTS AND METHODS: Immunohistopathologic studies
      were carried out on 26 tumor samples from a cohort of HR-NBL patients diagnosed
      at Children's Hospital of Philadelphia for the 2-year period from May 2003 to May
      2005. Blood from nine HLA-A2+ patients in this cohort was analyzed for T cells
      specific for the antiapoptotic protein survivin. RESULTS: Survivin protein was
      expressed by 26 of 26 tumors. In HLA-A2+ patients, circulating cytotoxic T
      lymphocytes (CTLs) specific for survivin were detected by peptide/major
      histocompatibility complex tetramer analysis in the blood of eight of nine
      children with HR-NBL at the time of diagnosis. Rather than being selectively
      rendered anergic in vivo, circulating survivin-specific CTLs were highly
      functional as shown by cytotoxicity and interferon gamma enzyme-linked immunospot
      assays in six of nine patients. Survivin-specific CD107a mobilization by T cells
      was found in five of five patients. By immunohistochemistry, tumor-infiltrating T
      cells were few or absent in 26 of 26 tumors. CONCLUSION: Children with HR-NBL
      harbor robust cellular immune responses to the universal tumor antigen survivin
      at the time of diagnosis, but intratumoral T cells are strikingly rare,
      suggesting a failure of cellular immunosurveillance. Efforts to develop novel
      therapies that increase T-cell trafficking into tumor nests are warranted.

PMID- 17179105
TI  - Phase II trial of a toll-like receptor 9-activating oligonucleotide in patients
      with metastatic melanoma.
AB  - PURPOSE: The recent identification of toll-like receptors (TLRs) and respective
      ligands allows the evaluation of novel dendritic cell (DC) -activating
      strategies. Stimulation of TLR9 directly activates human plasmacytoid DCs (PDCs)
      and indirectly induces potent innate immune responses in preclinical tumor
      models. We performed an open-label, multicenter, single-arm, phase II pilot trial
      with a TLR9-stimulating oligodeoxynucleotide in melanoma patients. PATIENTS AND
      METHODS: Patients with unresectable stage IIIb/c or stage IV melanoma received 6
      mg PF-3512676 weekly by subcutaneous injection for 24 weeks or until disease
      progression to evaluate safety as well as clinical and immunologic activity.
      Clinical and laboratory safety assessments were performed weekly; blood samples
      for immunological measurements were taken every 8 weeks. Tumor measurements were
      performed according to Response Evaluation Criteria in Solid Tumors. RESULTS:
      Twenty patients received PF-3512676 for a mean of 10.9 weeks with a mean of 10.7
      injections. Laboratory and nonlaboratory adverse events were limited, transient,
      and did not result in any withdrawals. Two patients experienced a confirmed
      partial response; one response is ongoing for 140+ weeks. Three patients
      experienced stable disease. Immunologic measurements revealed induction of an
      activated phenotype of PDC, elevation of serum levels of 2',5'-oligoadenylate, a
      surrogate marker of type I interferon production, and significant stimulation of
      natural killer cell cytotoxicity (the latter was associated with clinical
      benefit). CONCLUSION: These results indicate that TLR9-targeted therapy can
      stimulate innate immune responses in cancer patients, identify biomarkers that
      may be associated with TLR9-induced tumor regression, and encourage the design of
      follow-up studies to evaluate the ability of this therapeutic approach to target
      human cancer.

PMID- 17179108
TI  - Superiority of allogeneic hematopoietic stem-cell transplantation compared with
      chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia:
      results from ALL-BFM 90 and 95.
AB  - PURPOSE: The role of hematopoietic stem-cell transplantation (SCT) in first
      complete remission (CR1) for children with very high-risk (VHR) acute
      lymphoblastic leukemia (ALL) is still under critical discussion. PATIENTS AND
      METHODS: In the ALL-Berlin-Frankfurt-Munster (BFM) 90 and ALL-BFM 95 trials, 387
      patients were eligible for SCT if there was a matched sibling donor (MSD). T-cell
      ALL (T-ALL) patients with poor in vivo response to initial treatment represented
      the largest homogeneous subgroup within VHR patients. RESULTS: Of 191 high-risk
      (HR) T-ALL patients, 179 patients (94%) achieved CR1. Twenty-three patients
      received an MSD-SCT. Furthermore, in trial ALL-BFM 95, eight matched unrelated
      donors (MUDs) and five mismatched family donors (MMFDs) were used. The median
      time to SCT was 5 months (range, 2.4 to 10.8 months) from diagnosis. The 5-year
      disease-free survival (DFS) was 67% +/- 8% for 36 patients who received an SCT in
      CR1 and 42% +/- 5% for the 120 patients treated with chemotherapy alone having an
      event-free survival time of at least the median time to transplantation (Mantel
      Byar, P = .01). Overall survival (OS) rate for the SCT group was 67% +/- 8% at 5
      years, whereas patients treated with chemotherapy alone had an OS rate of 47% +/-
      5% at 5 years (Mantel-Byar, P = .01). Outcome of patients who received MSD-SCT
      versus MUD-/MMFD-SCT was comparable (DFS, 65% +/- 10% v 69% +/- 13%,
      respectively). However, relapses only occurred after MSD-SCT (eight of 23
      patients), whereas treatment-related mortality only occurred after MUD-/MMFD-SCT
      (four of 13 patients). CONCLUSION: SCT in CR1 is superior to treatment with
      chemotherapy alone for childhood HR-T-ALL.

PMID- 17179107
TI  - Survival and late effects in children with Hodgkin's lymphoma treated with
      MOPP/ABV and low-dose, extended-field irradiation.
AB  - PURPOSE: Reduced-intensity protocols for pediatric Hodgkin's lymphoma are aimed
      at preserving excellent relapse-free survival while decreasing the incidence of
      late effects. PATIENTS AND METHODS: We retrospectively reviewed the outcome of
      123 children treated consecutively for Hodgkin's lymphoma at a single
      institution. Patients with stages I-IIIB disease received three cycles of
      mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/ doxorubicin,
      bleomycin, and vinblastine (ABV) followed by 15 Gy of extended-field irradiation,
      while those with stage IV disease were treated with six to eight cycles of
      MOPP/ABV chemotherapy with or without radiotherapy. RESULTS: At a median follow
      up of 8.5 years (range, 1.4 to 15.5 years), the estimated 10-year overall
      survival and event-free survival are 94% (SE, 2.2%) and 88% (SE, 3.1%)
      respectively. There have been 12 treatment failures and six disease-related
      deaths. A very large mediastinal mass ( 50% of the maximal thoracic diameter) was
      associated with a 10-year event-free survival of 50% (SE, 14%) compared with 91%
      (SE, 4.0%) for smaller masses (P < .001). Late cardiopulmonary toxicity is
      largely absent, and the incidence of hypothyroidism is 14%. There have been no
      cases of secondary leukemia and four secondary solid malignancies observed to
      date. CONCLUSION: MOPP/ABV and low-dose, extended-field radiotherapy is an
      effective treatment for pediatric Hodgkin's lymphoma. With median follow-up of
      8.5 years, late cardiopulmonary effects and secondary malignancies from this
      treatment regimen are infrequent. Continued longitudinal observations,
      particularly for breast cancer in female patients and gonadotoxicity, will
      determine whether the goal of decreasing treatment-related complications while
      maintaining excellent survival has been achieved.

PMID- 17179109
TI  - Pathways through relapses and deaths of children with acute lymphoblastic
      leukemia: role of allogeneic stem-cell transplantation in Nordic data.
AB  - PURPOSE: Our focus was on patients with pediatric acute lymphoblastic leukemia
      (ALL) who experienced relapse or died without becoming transplantation
      candidates. The purpose was to outline measures needed to improve the outcome.
      PATIENTS AND METHODS: We analyzed our population-based 20-year data on 3,385
      Nordic children with ALL treated on Nordic Society for Pediatric Hematology and
      Oncology ALL protocols, and described the flow of these patients through
      relapses, remissions, and deaths as a result of toxicity, demonstrating where
      major patient losses occurred. RESULTS: In total, 854 patients (25%) had a first
      and 274 patients (8%) had a second ALL relapse. P for survival after the first
      relapse was .35 +/- .02. The induction mortality (2.2%, primary; 10.3%, first
      relapse; 26.3%, second relapse) and remission mortality (1%, first complete
      remission [1CR]; 19%, second CR [2CR]) were significant; transplantation-related
      mortality (TRM) only represented 15% (69 of 459) of the deaths as a result of
      toxicity. Of the 766 patients entering 2CR, 29% underwent transplantation (P for
      survival, .46 +/- .04), whereas 71% continued receiving chemotherapy (P for
      survival, .39 +/- .02). Children with stem-cell transplantation indications in
      2CR, if they did not undergo transplantation, generally died or had a second
      relapse. The patient groups that underwent transplantation in 1CR (n = 84), 2CR
      (n = 220), and > or = 3CR (n = 62) represented different risk profiles. Those
      with allogeneic stem-cell transplantation (allo-SCT) in > or = 3CR (P for
      survival, .37 +/- .07) had an ALL and first relapse with favorable features.
      CONCLUSION: Major patient losses occurred through mortality as a result of
      toxicity and resistant disease during the pathways before allo-SCT. After
      relapse, more patients were lost to mortality as a result of toxicity during
      conventional chemotherapy compared with TRM. After second relapse, the chance for
      rescue by allo-SCT in 3CR was minimal. The question of whether transplantation is
      recommended after ALL relapse should be carefully addressed, and more efficient
      relapse protocols should be launched.

PMID- 17179110
TI  - Attitudes and practices of breast cancer consultations regarding sexual issues: a
      nationwide survey of Japanese surgeons.
AB  - PURPOSE: To investigate doctors' current practices and attitudes and correlates
      of sexuality-related consultations in clinical encounters. METHODS: A nationwide,
      self-administered mail survey was conducted with 1,313 board-certified Japanese
      breast surgeons in August 2001. Surgeons were asked about their experiences
      regarding consultations about sexual issues, attitudes toward sex-related
      statements, and advice to a patient's hypothetical question on having sex after
      undergoing breast cancer treatment. RESULTS: Of the surveyed sample, 635 surgeons
      (50.3%) responded. Of these surgeons, 32.4% had been consulted about sexual
      issues by patients or families. Multiple logistic regression analysis suggested
      that female respondents (P < .01), respondents whose hospitals conduct a large
      number of breast cancer operations annually (P < .01), and respondents who agreed
      that "Surgeons have a professional responsibility to deal with patients' sexual
      issues" (P < .01) were significantly more likely to be consulted. Respondents who
      agreed that "If any sexual problem exists, patients will raise the topic before
      surgeons ask them" were less likely to be consulted (P < .05). Respondents'
      attitudes toward the sex-related statements showed that, although the majority
      recognized the importance of patients' sexuality-related concerns, they did not
      necessarily think that surgeons had a professional responsibility to deal with
      them. Regarding their advice in response to the question of "Are there any
      particular things to be careful about when having sex after surgery?", 32.8%
      answered "nothing in particular." CONCLUSION: This study shows that talking about
      sex-related topics is still repressed in patient-doctor encounters in Japan. It
      is an urgent matter to increase doctors' awareness and clinical skills to deal
      with patients' sexual issues.

PMID- 17179111
TI  - ASCO core values.

PMID- 17179112
TI  - Hemophagocytic alveolar rhabdomyosarcoma.

PMID- 17179113
TI  - Primary hepatic lymphoma 1 year after resection of hepatocellular carcinoma.

PMID- 17179115
TI  - Childhood papillary thyroid carcinoma with miliary pulmonary metastases.

PMID- 17179114
TI  - Hand-foot syndrome and seborrheic dermatitis-like rash induced by sunitinib in a
      patient with advanced renal cell carcinoma.

PMID- 17179116
TI  - Biosynthesis of eicosanoids and transcellular metabolism of leukotrienes in
      murine bone marrow cells.
AB  - Leukotriene B(4) (LTB(4)) biosynthesis by polymorphonuclear leukocytes (PMNs) is
      an important factor of inflammatory responses. PMNs also release LTA(4), an
      unstable intermediate that can be taken up by neighboring cells and metabolized
      into LTC(4). Most studies of LT synthesis have been carried out using human PMNs,
      but very little information is available about mouse PMNs. Mouse bone marrow PMNs
      were found to synthesize eicosanoids upon stimulation with A23187, fMLP, or
      zymosan. The major eicosanoids produced are LTB(4) and 5-hydroxyeicosatetraenoic
      acid, with some nonenzymatic products of LTA(4) hydrolysis. No cysteinyl
      leukotrienes were produced, in contrast to what was observed with human blood
      neutrophil preparations. Human megakaryoblast-like MEG-01 cells synthesized
      thromboxane B(2) and prostaglandin E(2) in response to A23187 but produced no 5
      lipoxygenase (5-LO)-derived eicosanoids. When mouse bone marrow cells (mBMCs) and
      MEG-01 cells were stimulated during coincubation, LTC(4) and LTD(4) were
      produced. Mouse peritoneal macrophages from 5-LO-deficient mice were able to
      synthesize LTC(4) when incubated with mBMCs from wild-type mice, demonstrating
      transcellular exchange of LTA(4) from mBMCs into murine peritoneal macrophages.
      These data demonstrate that murine bone marrow PMNs are a valid model for the
      study of LT biosynthesis, which now offers the possibility to investigate
      specific biochemical pathways through the use of transgenic mice.

PMID- 17179117
TI  - Robotic surgery in ophthalmology: reality or fantasy?

PMID- 17179118
TI  - Nature is teaching us to be humble in our quest to measure structure and function
      in glaucoma.

PMID- 17179119
TI  - Blood flow in glaucoma.

PMID- 17179121
TI  - First description of aniseikonia.

PMID- 17179120
TI  - Comparison of a new, minimally invasive strabismus surgery technique with the
      usual limbal approach for rectus muscle recession and plication.

PMID- 17179122
TI  - Evaluation of 1000 lacrimal ducts by dacryocystography.
AB  - AIM: To establish the association between the obstruction site, whether it is
      unilateral or bilateral, age group, and sex. METHODS: A retrospective
      observational study of 1000 lacrimal ducts of 500 consecutive patients seen in
      the Emilio Amorim Radiological Clinic, who were suspected of having lacrimal duct
      obstructions, was performed. RESULTS: Of the studied patients, 121 were men and
      379 were women. Their ages varied between 2 years and 93 years. 148 of the
      examinations were normal; in 298 the obstructions were unilateral and in 54 they
      were bilateral. The majority of the obstructions occurred at the valve of Krause.
      There was a significant difference in the correlation of the obstruction site
      with sex. The obstruction was total in 378 valves and partial in 28. Other
      findings included sinusitis, osteomas, bone fractures, fistulae, diverticulum,
      and lacrimal stones. CONCLUSION: Obstruction of the lacrimal ducts is normally
      total, unilateral, and sited at the valve of Krause. The obstruction of this
      valve predominantly affects women, whereas obstruction of the valve of Hasner
      mainly affects men. There was no significant difference in the distribution of
      obstructions by age group.

PMID- 17179123
TI  - Comparison of a new, minimally invasive strabismus surgery technique with the
      usual limbal approach for rectus muscle recession and plication.
AB  - AIM: To present a novel, minimally invasive strabismus surgery (MISS) technique
      for rectus muscle operations. METHODS: In this prospective study with a non
      concurrent, retrospective comparison group, the first 20 consecutive patients
      treated with MISS were matched by age, diagnosis and muscles operated on, with 20
      patients with a limbal opening operated on by the same surgeon at Kantonsspital,
      St Gallen, Switzerland. A total of 39 muscles were operated on. MISS is performed
      by applying two small radial cuts along the superior and inferior muscle margin.
      After muscle separation from surrounding tissue, a recession or plication is
      performed through the resulting tunnel. Alignment, binocular single vision,
      variations in vision, refraction, and number and types of complications during
      the first 6 postoperative months were registered. RESULTS: Visual acuity
      decreased at postoperative day 1 in both groups. The decrease was less pronounced
      in the group operated on with MISS (difference of decrease 0.14 logMAR, p<0.001).
      An abnormal lid swelling at day 1 was more frequent in the control group (21%,
      95% confidence interval (CI) 9% to 41%, 5/24 v 0%, 95% CI 0 to 13%, 0/25,
      p<0.05). No significant difference was found for final alignment, binocular
      single vision, other visual acuities, refractive changes or complications
      (allergic reactions, dellen formation, abnormal conjuctival findings). A
      conversion to a limbal opening was necessary in 5% (95% CI 2% to 17%, 2/39) of
      muscles. CONCLUSIONS: This study shows that this new, small-incision, minimal
      dissection technique is feasible. The MISS technique seems to be superior in the
      direct postoperative period as better visual acuities and less lid swelling were
      observed. Long-term results did not differ in the two groups.

PMID- 17179124
TI  - Preventing conjunctival autograft inversion in pterygium surgery.
AB  - BACKGROUND: Surgeon-dependent variables influencing pterygium surgical outcome
      using the conjunctival autograft technique include conjunctival retraction as a
      consequence of subepithelial contracting fibrous tissue, and autograft inversion
      causing necrosis and sloughing of the graft. METHOD: A simple and useful
      technique of pterygium excision is described, which helps to ensure the correct
      surface and linear orientations of the conjunctival autograft, and also defines
      the end point of adequate excision of the subepithelial connective tissue.
      CONCLUSION: This simple technique of defining the anterior surface and the
      centrifugal orientation with the letter "G" marked on the graft prevents reverse
      orientation of the graft.

PMID- 17179125
TI  - Linezolid-induced optic neuropathy: a mitochondrial disorder?
AB  - We report a case of bilateral mitochondrial optic neuropathies secondary to long
      term linezolid treatment, show the nature of recovery, review the findings in the
      literature and propose a potential mitochondrial mechanism for linezolid-induced
      mitochondrial optic neuropathy. This is an observational case report and
      literature review with presentation of the clinical course of linezolid
      mitochondrial optic neuropathies through clinical and psychophysical
      documentation. Main outcome measures included: visual acuity, funduscopical
      examinations and peripapillary retinal nerve fibre layer (PRNFL) optical
      coherence tomography (OCT). A 6-year-old boy presented with bilateral optic
      neuropathies secondary to 1 year of linezolid treatment for osteomyelitis of the
      mandible. On presentation, visual acuities were 20/400 in both eyes, with
      considerable optic disc oedema, hyperaemia and PRNFL swelling confirmed by OCT. 2
      weeks after the discontinuation of linezolid, visual acuities returned to 20/25
      in both eyes, with reduction in the optic disc oedema, hyperaemia and PRNFL
      swelling. 3 months after the discontinuation of linezolid treatment, visual
      acuities were stable at 20/20 in both eyes, with a marked decrease in PRNFL
      swelling confirmed by OCT, and the development of mild temporal optic disc pallor
      in both eyes. Doctors should be aware of impairments of vision among patients on
      long-term linezolid treatment and promptly discontinue treatment to prevent
      irreversible vision loss. The development and resolution of bilateral optic
      neuropathies with considerable PRNFL swelling in this patient provide insight
      into the more general rubric of mitochondrial optic neuropathies.

PMID- 17179126
TI  - Keratoconus associated with CSNB1.

PMID- 17179127
TI  - Combination treatment of intravenous immunoglobulin and cultivated oral mucosal
      epithelial transplantation for ocular cicatricial pemphigoid.

PMID- 17179128
TI  - The potential role of testosterone in central serous chorioretinopathy.

PMID- 17179129
TI  - High-speed, ultra-high-resolution optical coherence tomography of acute macular
      neuroretinopathy.

PMID- 17179130
TI  - The aetiology and associations of conjunctival intraepithelial neoplasia: further
      evidence.

PMID- 17179131
TI  - Cytological vitreous findings in a patient with infantile neurological cutaneous
      and articular (CINCA) syndrome.

PMID- 17179132
TI  - Severe decompression retinopathy after medical treatment of acute primary angle
      closure.

PMID- 17179133
TI  - Iatrogenic central retinal artery occlusion during treatment for epistaxis.

PMID- 17179134
TI  - Patient safety and ophthalmic surgery marking: which side are you on?

PMID- 17179135
TI  - Patching treatment and bullying.

PMID- 17179136
TI  - National Patient Safety Agency protocol for preoperative site marking.

PMID- 17179137
TI  - Promoting physical activity among South Asian women with coronary heart disease
      and diabetes: what might help?
AB  - BACKGROUND: People of South Asian origin have higher mortality and morbidity from
      coronary heart disease (CHD) and diabetes than those of European origin. However,
      physical activity, of established value in primary and secondary prevention,
      appears lower among South Asians. OBJECTIVE: To explore influences on, and
      attitudes towards, physical activity among South Asian women with CHD and
      diabetes to inform secondary prevention strategies. METHODS: Exploratory
      qualitative study with women aged 26-70 years of varying South Asian ethnicity,
      religion and socio-economic background with CHD and/or non-insulin-dependent
      diabetes were recruited from primary care practices in the UK. RESULTS: The
      beneficial use of physical activity to improve and limit progression of their
      disease was largely unrecognized by the women interviewed. They were uncertain
      what type and level of physical activity was appropriate and safe for them. They
      operated their own threshold for physical activity in relation to their
      condition, which they were afraid to exceed. Specific guidance from health
      professionals was lacking. Respondents emphasized the cultural importance of
      being active day to day, rather than the 'Western' concepts of organized
      exercise. However, women's principal motivations and attitudes towards physical
      activity, to loose weight, socialize and maintain independence, were culturally
      similar to 'majority' populations. CONCLUSIONS: Better health professional
      guidance on appropriate physical activity, its health benefits and its safety is
      needed for this highly at-risk group. Promoting informal moderate-intensity
      physical activity may help. Strategies should avoid any tendency to overemphasize
      cultural barriers noting greater similarities than differences between cultural
      groups.

PMID- 17179139
TI  - Not born equal: increased rate asymmetry in relocated and retrotransposed rodent
      gene duplicates.
AB  - Duplicated genes frequently evolve at different rates. This asymmetry is evidence
      of natural selection's ability to discriminate between the 2 copies, subjecting
      them to different levels of purifying selection or even permitting adaptive
      evolution of one or both copies. However, if gene duplication creates pairs of
      protein-coding sequences that are initially identical, this raises the question
      of how selection tells the 2 copies apart. Here, we investigated asymmetric
      sequence divergence of recently duplicated genes in rodents and related this to 2
      possible sources of such asymmetry: gene relocation as a consequence of
      duplication and retrotransposition as a mechanism of gene duplication. We found
      that most young rodent duplicates that have been relocated were created by
      retrotransposition. The degree of rate asymmetry in gene pairs where one copy has
      been relocated (either by retrotransposition or DNA-based duplication) is greater
      than in pairs formed by local DNA-based duplication events. Furthermore, by
      considering the direction of transposition for distant duplicates, we found a
      consistent tendency for retrogenes to undergo accelerated protein evolution
      relative to their static paralogs, whereas DNA-based transpositions showed no
      such tendency. Finally, we demonstrate that the faster sequence evolution of
      retrogenes correlates with the profound alteration of their expression pattern
      that is precipitated by retrotransposition.

PMID- 17179138
TI  - Drosophila mojoless, a retroposed GSK-3, has functionally diverged to acquire an
      essential role in male fertility.
AB  - Retroposition is increasingly recognized as an important mechanism for the
      acquisition of new genes. We show that a glycogen synthase kinase-3 gene, shaggy
      (sgg), retroposed at least 50 MYA in the Drosophila genus to generate a new gene,
      mojoless (mjl). We have extensively analyzed the function of mjl and examined its
      functional divergence from the parental gene sgg in Drosophila melanogaster.
      Unlike Sgg, which is expressed in many tissues of both sexes, Mjl is expressed
      specifically in the male germ line, where it is required for male germ line
      survival. Our analysis indicates that mjl has acquired a specific function in the
      maintenance of male germ line viability. However, it has not completely lost its
      ancestral biochemical function and can partially compensate for loss of the
      parental gene sgg when ectopically expressed in somatic cells. We postulate that
      mjl has undergone functional diversification and is now under stabilizing
      selection in the Drosophila genus.

PMID- 17179140
TI  - Muscle-bound? A tissue-selective nonsteroidal androgen receptor modulator.

PMID- 17179143
TI  - Regulation of apoptosis and differentiation by p53 in human embryonic stem cells.
AB  - The essentially infinite expansion potential and pluripotency of human embryonic
      stem cells (hESCs) makes them attractive for cell-based therapeutics. In contrast
      to mouse embryonic stem cells (mESCs), hESCs normally undergo high rates of
      spontaneous apoptosis and differentiation, making them difficult to maintain in
      culture. Here we demonstrate that p53 protein accumulates in apoptotic hESCs
      induced by agents that damage DNA. However, despite the accumulation of p53, it
      nevertheless fails to activate the transcription of its target genes. This
      inability of p53 to activate its target genes has not been observed in other cell
      types, including mESCs. We further demonstrate that p53 induces apoptosis of
      hESCs through a mitochondrial pathway. Reducing p53 expression in hESCs in turn
      reduces both DNA damage-induced apoptosis as well as spontaneous apoptosis.
      Reducing p53 expression also reduces spontaneous differentiation and slows the
      differentiation rate of hESCs. Our studies reveal the important roles of p53 as a
      critical mediator of human embryonic stem cells survival and differentiation.

PMID- 17179144
TI  - A Proteasome-regulated glycogen synthase kinase-3 modulates disease response in
      plants.
AB  - Glycogen synthase kinase-3 (GSK-3) is a key player in various important signaling
      pathways in animals. The activity of GSK-3 is known to be modulated by protein
      phosphorylation and differential complex formation. However, little information
      is available regarding the function and regulation of plant GSK-3/shaggy-like
      kinases (GSKs). Analysis of the in vivo kinase activity of MsK1, a GSK from
      Medicago sativa, revealed that MsK1 is active in healthy plants and that MsK1
      activity is down-regulated by the elicitor cellulase in a time- and dose
      dependent manner. Surprisingly, cellulase treatment triggered the degradation of
      the MsK1 protein in a proteasome-dependent manner suggesting a novel mechanism of
      GSK-3 regulation. Inhibition of MsK1 kinase activity and degradation of the
      protein were two successive processes that could be uncoupled. In a transgenic
      approach, stimulus-induced inhibition of MsK1 was impeded by constant
      replenishment of MsK1 by a strong constitutive promoter. MsK1 overexpressing
      plants exhibited enhanced disease susceptibility to the virulent bacterial
      pathogen Pseudomonas syringae. MAP kinase activation in response to pathogen
      infection was compromised in plants with elevated MsK1 levels. These data
      strongly suggest that tight regulation of the plant GSK-3, MsK1, may be important
      for innate immunity to limit the severity of virulent bacterial infection.

PMID- 17179145
TI  - Oligomerization of the UDP-glucuronosyltransferase 1A proteins: homo- and
      heterodimerization analysis by fluorescence resonance energy transfer and co
      immunoprecipitation.
AB  - UDP-glucuronosyltransferases (UGTs) are membrane-bound proteins localized to the
      endoplasmic reticulum and catalyze the formation of beta-d-glucopyranosiduronic
      acids (glucuronides) using UDP-glucuronic acid and acceptor substrates such as
      drugs, steroids, bile acids, xenobiotics, and dietary nutrients. Recent
      biochemical evidence indicates that the UGT proteins may oligomerize in the
      membrane, but conclusive evidence is still lacking. In the present study, we have
      used fluorescence resonance energy transfer (FRET) to study UGT1A oligomerization
      in live cells. This technique demonstrated that UGT1A1, UGT1A3, UGT1A4, UGT1A6,
      UGT1A7, UGT1A8, UGT1A9, and UGT1A10 self-oligomerize (homodimerize). Heterodimer
      interactions were also explored, and it was determined that UGT1A1 was capable of
      binding with UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10. In
      addition to the in vivo FRET analysis, UGT1A protein-protein interactions were
      demonstrated through co-immunoprecipitation experiments. Co-expression of
      hemagglutinin-tagged and cyan fluorescent protein-tagged UGT1A proteins, followed
      by immunoprecipitation with anti-hemagglutinin beads, illustrated the potential
      of each UGT1A protein to homodimerize. Co-immunoprecipitation results also
      confirmed that UGT1A1 was capable of forming heterodimer complexes with all of
      the UGT1A proteins, corroborating the FRET results in live cells. These
      preliminary studies suggest that the UGT1A family of proteins form oligomerized
      complexes in the membrane, a property that may influence function and substrate
      selectivity.

PMID- 17179146
TI  - Inactivation of Corynebacterium glutamicum NCgl0452 and the role of MgtA in the
      biosynthesis of a novel mannosylated glycolipid involved in lipomannan
      biosynthesis.
AB  - Mycobacterium tuberculosis PimB has been demonstrated to catalyze the addition of
      a mannose residue from GDP-mannose to a monoacylated phosphatidyl-myo-inositol
      mannoside (Ac(1)PIM(1)) to generate Ac(1)PIM(2). Herein, we describe the
      disruption of its probable orthologue Cg-pimB and the chemical analysis of
      glycolipids and lipoglycans isolated from wild type Corynebacterium glutamicum
      and the C. glutamicum::pimB mutant. Following a careful analysis, two related
      glycolipids, Gl-A and Gl-X, were found in the parent strain, but Gl-X was absent
      from the mutant. The biosynthesis of Gl-X was restored in the mutant by
      complementation with either Cg-pimB or Mt-pimB. Subsequent chemical analyses
      established Gl-X as 1,2-di-O-C(16)/C(18:1)-(alpha-d-mannopyranosyl)-(1-->4)
      (alpha-d-glucopyranosyluronic acid)-(1-->3)-glycerol (ManGlcAGroAc(2)) and Gl-A
      as the precursor, GlcAGroAc(2). In addition, C. glutamicum::pimB was still able
      to produce Ac(1)PIM(2), suggesting that Cg-PimB catalyzes the synthesis of
      ManGlcAGroAc(2) from GlcAGroAc(2). Isolation of lipoglycans from C. glutamicum
      led to the identification of two related lipoglycans. The larger lipoglycan
      possessed a lipoarabinomannan-like structure, whereas the smaller lipoglycan was
      similar to lipomannan (LM). The absence of ManGlcA-GroAc(2) in C.
      glutamicum::pimB led to a severe reduction in LM. These results suggested that
      ManGlcAGroAc(2) was further extended to an LM-like molecule. Complementation of
      C. glutamicum::pimB with Cg-pimB and Mt-pimB led to the restoration of LM
      biosynthesis. As a result, Cg-PimB, which we have assigned as MgtA, is now
      clearly defined as a GDP-mannose-dependent alpha-mannosyltransferase from our in
      vitro analyses and is involved in the biosynthesis of ManGlcAGroAc(2).

PMID- 17179147
TI  - Environment of the active site region of RseP, an Escherichia coli regulated
      intramembrane proteolysis protease, assessed by site-directed cysteine
      alkylation.
AB  - Regulated intramembrane proteolysis (RIP) plays crucial roles in both prokaryotic
      and eukaryotic organisms. Proteases for RIP cleave transmembrane regions of
      substrate membrane proteins. However, the molecular mechanisms for the
      proteolysis of membrane-embedded transmembrane sequences are largely unknown.
      Here we studied the environment surrounding the active site region of RseP, an
      Escherichia coli S2P ortholog involved in the sigma(E) pathway of
      extracytoplasmic stress responses. RseP has two presumed active site motifs,
      HEXXH and LDG, located in membrane-cytoplasm boundary regions. We examined the
      reactivity of cysteine residues introduced within or in the vicinity of these two
      active site motifs with membrane-impermeable thiol-alkylating reagents under
      various conditions. The active site positions were inaccessible to the reagents
      in the native state, but many of them became partially modifiable in the presence
      of a chaotrope, while requiring simultaneous addition of a chaotrope and a
      detergent for full modification. These results suggest that the active site of
      RseP is not totally embedded in the lipid phase but located within a
      proteinaceous structure that is partially exposed to the aqueous milieu.

PMID- 17179148
TI  - Mouse and human granzyme B have distinct tetrapeptide specificities and abilities
      to recruit the bid pathway.
AB  - Granzyme B is an important mediator of cytotoxic lymphocyte granule-induced death
      of target cells, accomplishing this through cleavage of Bid and cleavage and
      activation of caspases as well as direct cleavage of downstream substrates.
      Significant controversy exists regarding the primary pathways used by granzyme B
      to induce cell death, perhaps arising from the use of different
      protease/substrate combinations in different studies. The primary sequence of
      human, rat, and mouse granzymes B is well conserved, and the substrate
      specificity and crystal structure of the human and rat proteases are extremely
      similar. Although little is known about the substrate specificity of mouse
      granzyme B, recent studies suggest that it may differ significantly from the
      human protease. In these studies we show that the specificities of human and
      mouse granzymes B differ significantly. Human and mouse granzyme B cleave species
      specific procaspase-3 more efficiently than the unmatched substrates. The
      distinct specificities of human and mouse granzyme B highlight a previously
      unappreciated requirement for Asp(192) in the acquisition of catalytic activity
      upon cleavage of procaspase-3 at Asp(175). Although human granzyme B efficiently
      cleaves human or mouse Bid, these substrates are highly resistant to cleavage by
      the mouse protease, strongly indicating that the Bid pathway is not a major
      primary mediator of the effects of mouse granzyme B. These studies provide
      important insights into the substrate specificity and function of the granzyme B
      pathway in different species and highlight that caution is essential when
      designing and interpreting experiments with different forms of granzyme B.

PMID- 17179149
TI  - Inhibition of hepatic phosphatidylcholine synthesis by 5-aminoimidazole-4
      carboxamide-1-beta-4-ribofuranoside is independent of AMP-activated protein
      kinase activation.
AB  - 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAr), a commonly used
      indirect activator of AMP-activated protein kinase (AMPK), inhibits
      phosphatidylcholine (PC) biosynthesis in freshly isolated hepatocytes. In all
      nucleated mammalian cells, PC is synthesized from choline via the Kennedy (CDP
      choline) pathway. The purpose of our study was to provide direct evidence that
      AMPK regulates phospholipid biosynthesis and to elucidate the mechanism(s) by
      which AMPK inhibits hepatic PC synthesis. Incubations of hepatocytes with AICAr
      resulted in a dose-dependent activation of AMPK and inhibition of PC
      biosynthesis. Surprisingly, adenoviral delivery of constitutively active AMPK did
      not alter PC biosynthesis. In addition, expression of dominant negative mutants
      of AMPK was unable to block the AICAr-dependent inhibition of PC biosynthesis,
      indicating that AICAr was acting independently of AMPK activation. Determination
      of aqueous intermediates of the CDP-choline pathway indicated that choline
      kinase, the first enzyme in the pathway, was inhibited by AICAr administration.
      Flux through the CDP-choline pathway was directly correlated to the level of
      intracellular ATP concentrations. Therefore, it is possible that inhibition of PC
      biosynthesis is another process by which the cell can reduce ATP consumption in
      times of energetic stress. However, unlike cholesterol and triacylglycerol
      biosynthesis, PC production is not regulated by AMPK.

PMID- 17179150
TI  - Neutralization of acidic residues in helix II stabilizes the folded conformation
      of acyl carrier protein and variably alters its function with different enzymes.
AB  - Acyl carrier protein (ACP), a small protein essential for bacterial growth and
      pathogenesis, interacts with diverse enzymes during the biosynthesis of fatty
      acids, phospholipids, and other specialized products such as lipid A. NMR and
      hydrodynamic studies have previously shown that divalent cations stabilize native
      helical ACP conformation by binding to conserved acidic residues at two sites (A
      and B) at either end of the "recognition" helix II. To examine the roles of these
      amino acids in ACP structure and function, site-directed mutagenesis was used to
      replace individual site A (Asp-30, Asp-35, Asp-38) and site B (Glu-47, Glu-53,
      Asp-56) residues in recombinant Vibrio harveyi ACP with the corresponding amides,
      along with combined mutations at each site (SA, SB) or both sites (SA/SB). Like
      native V. harveyi ACP, all individual mutants were unfolded at neutral pH but
      adopted a helical conformation in the presence of millimolar Mg(2+) or upon fatty
      acylation. Mg(2+) binding to sites A or B independently stabilized native ACP
      conformation, whereas mutant SA/SB was folded in the absence of Mg(2+),
      suggesting that charge neutralization is largely responsible for ACP
      stabilization by divalent cations. Asp-35 in site A was critical for holo-ACP
      synthase activity, while acyl-ACP synthetase and UDP-N-acetylglucosamine
      acyltransferase (LpxA) activities were more affected by mutations in site B. Both
      sites were required for fatty acid synthase activity. Overall, our results
      indicate that divalent cation binding site mutations have predicted effects on
      ACP conformation but unpredicted and variable consequences on ACP function with
      different enzymes.

PMID- 17179151
TI  - Activated epidermal growth factor receptor induces integrin alpha2
      internalization via caveolae/raft-dependent endocytic pathway.
AB  - Elevated expression or activity of the epidermal growth factor (EGF) receptor is
      common in ovarian cancer and is associated with poor patient prognosis. Our
      previous studies demonstrated that expression of the constitutively active mutant
      form of the EGF receptor (EGFRvIII) in ovarian cancer cells led to reduction in
      integrin alpha2 surface expression, defects in cell spreading, and disruption of
      focal adhesions. Inhibition of EGFRvIII catalytic activity reversed the response,
      suggesting that EGF receptor activation regulates integrin alpha2. In this study
      we found that EGF treatment resulted in a transient loss of integrin alpha2 from
      the cell surface. Before EGF stimulation, integrin alpha2 and EGF receptors were
      associated based on biochemical and immuno-colocalization approaches. After EGF
      treatment, EGF receptor and integrin alpha2 were internalized and segregated into
      different compartments. Integrin alpha2, but not EGF receptor, was associated
      with caveolin-1 and GM1 (Gal_1,3GalNAc_1,4(Neu5Ac-_ 2,3)Gal_1,4Glc_1,1-ceramide)
      gangliosides, suggesting caveolae-mediated endocytosis. Moreover, integrin alpha2
      was subsequently targeted to the Golgi apparatus and the endoplasmic reticulum.
      Together, these findings demonstrate that activated EGF receptor transiently
      modulates integrin alpha2 cell surface expression and stimulates integrin alpha2
      trafficking via caveolae/raft-mediated endocytosis, representing a novel
      mechanism by which the EGF receptor may regulate integrin-mediated cell behavior.

PMID- 17179152
TI  - Oxygen tension regulates the stability of insulin receptor substrate-1 (IRS-1)
      through caspase-mediated cleavage.
AB  - The insulin and insulin-like growth factor-1 (IGF-1) receptors mediate signaling
      for energy uptake and growth through insulin receptor substrates (IRSs), which
      interact with these receptors as well as with downstream effectors. Oxygen is
      essential not only for ATP production through oxidative phosphorylation but also
      for many cellular processes, particularly those involved in energy homeostasis.
      The oxygen tension in vivo is significantly lower than that in the air and can
      vary widely depending on the tissue as well as on perfusion and oxygen
      consumption. How oxygen tension affects IRSs and their functions is poorly
      understood. Our findings indicate that transient hypoxia (1% oxygen) leads to
      caspase-mediated cleavage of IRS-1 without inducing cell death. The IRS-1 protein
      level rebounds rapidly upon return to normoxia. Protein tyrosine phosphatases
      (PTPs) appear to be important for the IRS-1 cleavage because tyrosine
      phosphorylation of the insulin receptor was decreased in hypoxia and IRS-1
      cleavage could be blocked either with H(2)O(2) or with vanadate, each of which
      inhibits PTPs. Activity of Akt, a downstream effector of insulin and IGF-1
      signaling that is known to suppress caspase activation, was suppressed in
      hypoxia. Overexpression of dominant-negative Akt led to IRS-1 cleavage even in
      normoxia, and overexpression of constitutively active Akt partially suppressed
      IRS-1 cleavage in hypoxia, suggesting that hypoxia-mediated suppression of Akt
      may induce caspase-mediated IRS-1 cleavage. In conclusion, our study elucidates a
      mechanism by which insulin and IGF-1 signaling can be matched to the oxygen level
      that is available to support growth and energy metabolism.

PMID- 17179153
TI  - Cloning of ovocalyxin-36, a novel chicken eggshell protein related to
      lipopolysaccharide-binding proteins, bactericidal permeability-increasing
      proteins, and plunc family proteins.
AB  - The avian eggshell is a composite biomaterial composed of noncalcifying eggshell
      membranes and the overlying calcified shell matrix. The shell is deposited in a
      uterine fluid where the concentration of different protein species varies at
      different stages of its formation. The role of avian eggshell proteins during
      shell formation remains poorly understood, and we have sought to identify and
      characterize the individual components in order to gain insight into their
      function during elaboration of the eggshell. In this study, we have used direct
      sequencing, immunochemistry, expression screening, and EST data base mining to
      clone and characterize a 1995-bp full-length cDNA sequence corresponding to a
      novel chicken eggshell protein that we have named Ovocalyxin-36 (OCX-36).
      Ovocalyxin-36 protein was only detected in the regions of the oviduct where egg
      shell formation takes place; uterine OCX-36 message was strongly up-regulated
      during eggshell calcification. OCX-36 localized to the calcified eggshell
      predominantly in the inner part of the shell, and to the shell membranes. BlastN
      data base searching indicates that there is no mammalian version of OCX-36;
      however, the protein sequence is 20-25% homologous to proteins associated with
      the innate immune response as follows: lipopolysaccharide-binding proteins,
      bactericidal permeability-increasing proteins, and Plunc family proteins.
      Moreover, the genomic organization of these proteins and OCX-36 appears to be
      highly conserved. These observations suggest that OCX-36 is a novel and specific
      chicken eggshell protein related to the superfamily of lipopolysaccharide-binding
      proteins/bactericidal permeability-increasing proteins and Plunc proteins. OCX-36
      may therefore participate in natural defense mechanisms that keep the egg free of
      pathogens.

PMID- 17179154
TI  - Scaffolding as an organizing principle in trans-translation. The roles of small
      protein B and ribosomal protein S1.
AB  - A eubacterial ribosome stalled on a defective mRNA can be released through a
      quality control mechanism referred to as trans-translation, which depends on the
      coordinating binding actions of transfer-messenger RNA, small protein B, and
      ribosome protein S1. By means of cryo-electron microscopy, we obtained a map of
      the complex composed of a stalled ribosome and small protein B, which appears
      near the decoding center. This result suggests that, when lacking a codon, the A
      site on the small subunit is a target for small protein B. To investigate the
      role of S1 played in trans-translation, we obtained a cryo-electron microscopic
      map, including a stalled ribosome, transfer-messenger RNA, and small protein Bs
      but in the absence of S1. In this complex, several connections between the 30 S
      subunit and transfer-messenger RNA that appear in the +S1 complex are no longer
      found. We propose the unifying concept of scaffolding for the roles of small
      protein B and S1 in binding of transfer-messenger RNA to the ribosome during
      trans-translation, and we infer a pathway of sequential binding events in the
      initial phase of trans-translation.

PMID- 17179155
TI  - Geminin prevents rereplication during xenopus development.
AB  - To maintain a stable genome, it is essential that replication origins fire only
      once per cell cycle. The protein Geminin is thought to prevent a second round of
      DNA replication by inhibiting the essential replication factor Cdt1. Geminin also
      affects the development of several different organs by binding and inhibiting
      transcription factors and chromatin-remodeling proteins. It is not known if the
      defects in Geminin-deficient organisms are due to overreplication or to effects
      on cell differentiation. We previously reported that Geminin depletion in Xenopus
      causes early embryonic lethality due to a Chk1-dependent G(2) cell cycle arrest
      just after the midblastula transition. Here we report that expressing a non
      Geminin-binding Cdt1 mutant in Xenopus embryos exactly reproduces the phenotype
      of geminin depletion. Expressing the same mutant in replication extracts induces
      a partial second round of DNA replication within a single S phase. We conclude
      that Geminin is required to suppress a second round of DNA replication in vivo
      and that the phenotype of Geminin-depleted Xenopus embryos is caused by abnormal
      Cdt1 regulation. Expressing a nondegradable Cdt1 mutant in embryos also
      reproduces the Geminin-deficient phenotype. In cell extracts, the nondegradable
      mutant has no effect by itself but augments the amount of rereplication observed
      when Geminin is depleted. We conclude that Cdt1 is regulated both by Geminin
      binding and by degradation.

PMID- 17179156
TI  - AMP-activated protein kinase mediates carotid body excitation by hypoxia.
AB  - Early detection of an O2 deficit in the bloodstream is essential to initiate
      corrective changes in the breathing pattern of mammals. Carotid bodies serve an
      essential role in this respect; their type I cells depolarize when O2 levels
      fall, causing voltage-gated Ca2+ entry. Subsequent neurosecretion elicits
      increased afferent chemosensory fiber discharge to induce appropriate changes in
      respiratory function (1). Although depolarization of type I cells by hypoxia is
      known to arise from K+ channel inhibition, the identity of the signaling pathway
      has been contested, and the coupling mechanism is unknown (2). We tested the
      hypothesis that AMP-activated protein kinase (AMPK) is the effector of hypoxic
      chemotransduction. AMPK is co-localized at the plasma membrane of type I cells
      with O2-sensitive K+ channels. In isolated type I cells, activation of AMPK using
      5-aminoimidazole-4-carboxamide riboside (AICAR) inhibited O2-sensitive K+
      currents (carried by large conductance Ca2+-activated (BKCa) channels and TASK
      (tandem pore, acid-sensing potassium channel)-like channels, leading to plasma
      membrane depolarization, Ca2+ influx, and increased chemosensory fiber discharge.
      Conversely, the AMPK antagonist compound C reversed the effects of hypoxia and
      AICAR on type I cell and carotid body activation. These results suggest that AMPK
      activation is both sufficient and necessary for the effects of hypoxia.
      Furthermore, AMPK activation inhibited currents carried by recombinant BKCa
      channels, whereas purified AMPK phosphorylated thealpha subunit of the channel in
      immunoprecipitates, an effect that was stimulated by AMP and inhibited by
      compound C. Our findings demonstrate a central role for AMPK in stimulus-response
      coupling by hypoxia and identify for the first time a link between metabolic
      stress and ion channel regulation in an O2-sensing system.

PMID- 17179157
TI  - A critical role for system A amino acid transport in the regulation of dendritic
      development by brain-derived neurotrophic factor (BDNF).
AB  - Dendritic development is essential for the establishment of a functional nervous
      system. Among factors that control dendritic development, brain-derived
      neurotrophic factor (BDNF) has been shown to regulate dendritic length and
      complexity of cortical neurons. However, the cellular and molecular mechanisms
      that underlie these effects remain poorly understood. In this study, we examined
      the role of amino acid transport in mediating the effects of BDNF on dendritic
      development. We show that BDNF increases System A amino acid transport in
      cortical neurons by selective up-regulation of the sodium-coupled neutral amino
      acid transporter (SNAT)1. Up-regulation of SNAT1 expression and System A activity
      is required for the effects of BDNF on dendritic growth and branching of cortical
      neurons. Further analysis revealed that induction of SNAT1 expression and System
      A activity by BDNF is necessary in particular to enhance synthesis of tissue-type
      plasminogen activator, a protein that we demonstrate to be essential for the
      effects of BDNF on cortical dendritic morphology. Together, these data reveal
      that stimulation of neuronal differentiation by BDNF requires the up-regulation
      of SNAT1 expression and System A amino acid transport to meet the increased
      metabolic demand associated with the enhancement of dendritic growth and
      branching.

PMID- 17179158
TI  - Statin-induced Ras activation integrates the phosphatidylinositol 3-kinase signal
      to Akt and MAPK for bone morphogenetic protein-2 expression in osteoblast
      differentiation.
AB  - Lovastatin promotes osteoblast differentiation by increasing bone morphogenetic
      protein-2 (BMP-2) expression. We demonstrate that lovastatin stimulates tyrosine
      phosphorylation of the p85 regulatory subunit of phosphatidylinositol 3-kinase
      (PI3K), leading to an increase in its kinase activity in osteoblast cells.
      Inhibition of PI3K ameliorated expression of the osteogenic markers alkaline
      phosphatase, type I collagen, osteopontin, and BMP-2. Expression of dominant
      negative PI3K and PTEN, an inhibitor of PI3K signaling, significantly attenuated
      lovastatin-induced transcription of BMP-2. Akt kinase was also activated in a
      PI3K-dependent manner. However, our data suggest involvement of an additional
      signaling pathway. Lovastatin-induced Erk1/2 activity contributed to BMP-2
      transcription. Inhibition of PI3K abrogated Erk1/2 activity in response to
      lovastatin, indicating the presence of a signal relay between them. We provide,
      as a mechanism of this cross-talk, the first evidence that lovastatin stimulates
      rapid activation of Ras, which associates with and activates PI3K in the plasma
      membrane, which in turn regulates Akt and Erk1/2 to induce BMP-2 expression for
      osteoblast differentiation.

PMID- 17179159
TI  - Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially
      transmits signals to histone deacetylase 4 in cardiac cells.
AB  - Class II histone deacetylases (HDACs) act as repressors of cardiac hypertrophy,
      an adaptative response of the heart characterized by a reprogramming of fetal
      cardiac genes. Prolonged hypertrophy often leads to dilated cardiomyopathy and
      heart failure. Upstream endogenous regulators of class II HDACs that regulate
      hypertrophic growth are just beginning to emerge. Here we demonstrate that the
      delta B isoform of calcium/calmodulin-dependent protein kinase II (CaMKIIdeltaB),
      known to promote cardiac hypertrophy, transmits signals specifically to HDAC4 but
      not other class II HDACs. CaMKIIdeltaB efficiently phosphorylates both a
      glutathione S-transferase (GST)-HDAC4 fragment spanning amino acids 207-311 and
      full-length FLAG-HDAC4 but not the equivalents in HDAC5. Although previous
      studies in skeletal muscle cells have shown that HDAC4 lacking serine 246 cannot
      be phosphorylated by CaMKI/IV, a similar mutant is still phosphorylated by
      CaMKIIdeltaB. Importantly, mutation of serine 210 to alanine totally abolishes
      phosphorylation of the GST fragment and significantly reduces phosphorylation of
      full-length HDAC by CaMKIIdeltaB. RNA interference knockdown of CaMKIIdeltaB
      prevents the effects of hypertrophic stimuli. Overexpression of CaMKIIdeltaB in
      primary neonatal cardiomyocytes increases the activity of the Mef2 transcription
      factor and completely rescues HDAC4-mediated repression of MEF2 but only
      partially rescues inhibition by HDAC5 or the HDAC4 S210A mutant. CaMKIIdeltaB
      strongly interacts with HDAC4 in cells but not with HDAC5. These results
      demonstrate that CaMKIIdeltaB preferentially targets HDAC4, and this involves
      serine 210. These findings identify HDAC4 as a specific downstream substrate of
      CaMKIIdeltaB in cardiac cells and have broad applications for the signaling
      pathways leading to cardiac hypertrophy and heart failure.

PMID- 17179160
TI  - Versatile roles of R-Ras GAP in neurite formation of PC12 cells and embryonic
      vascular development.
AB  - Ras GTPase-activating proteins (GAP) are negative regulators of Ras that convert
      active Ras-GTP to inactive Ras-GDP. R-Ras GAP is a membrane-associated molecule
      with stronger GAP activity for R-Ras, an activator of integrin, than H-Ras. We
      found that R-Ras GAP is down-regulated during neurite formation in rat
      pheochromocytoma PC12 cells by nerve growth factor (NGF), which is blocked by the
      transient expression of R-Ras gap or dominant negative R-ras cDNA. By
      establishing a PC12 subclone that stably expresses exogenous R-Ras GAP, it was
      found that NGF reduced endogenous R-Ras GAP but not exogenous R-Ras GAP,
      suggesting that down-regulation of R-Ras GAP occurs at the transcription level.
      To clarify the physiological role of R-Ras GAP, we generated mice that express
      mutant Ras GAP with knocked down activity. While heterozygotes are normal,
      homozygous mice die at E12.5-13.5 of massive subcutaneous and intraparenchymal
      bleeding, probably due to underdeveloped adherens junctions between capillary
      endothelial cells. These results show essential roles of R-Ras GAP in development
      and differentiation: its expression is needed for embryonic development of blood
      vessel barriers, whereas its down-regulation facilitates NGF-induced neurite
      formation of PC12 cells via maintaining activated R-Ras.

PMID- 17179161
TI  - Recovery of hippocampus-related functions in chronic alcoholics during monitored
      long-term abstinence.
AB  - AIMS: The hippocampus (HC) is characterized by high vulnerability to noxious
      influence, but also by a considerable regenerative potential. Although deficits
      in HC-related functions are among the most commonly reported cognitive sequelae
      in alcoholism, little and conflicting information is available concerning
      regeneration upon abstinence. The present study has been designed to evaluate (i)
      the frequency of measurable dysfunction in so called HC tests and (ii) its
      predictive value for risk to relapse in a cohort of 50 severely affected chronic
      alcoholic patients and (iii) to monitor recovery of HC-related functions upon
      strict abstention from alcohol. METHODS: Patients underwent a 2-year
      neuropsychological follow-up including HC-associated tests (Verbal Learning Test,
      VLT; Nonverbal Learning Test, NVLT; 'City Map Test' of Learning and Memory Test,
      LGT-3), as well as tests of intelligence and attention in the framework of OLITA
      (Outpatient Long-Term Intensive Therapy for Alcoholics), a programme with careful
      abstinence monitoring. RESULTS: At study entry, 30/50 (60%) alcoholics had HC
      dysfunction which tended to predict a lower long-term abstinence probability (P =
      0.058). Of the subgroup that could be followed under conditions of strictly
      monitored alcohol abstinence (n = 32; age 44.7 +/- 6.2 years; 23 men, 9 women),
      53% (17/32) exhibited distinct HC dysfunction at inclusion which returned to
      normal after 2 years. Patients with initially normal HC function (9/32) and
      patients with additional brain damage of different aetiologies (6/32) failed to
      show improvement on HC-related tests. While the former displayed stably normal HC
      test performance, the latter remained on a performance level below normal.
      CONCLUSIONS: Demonstrating slow but remarkable regeneration of HC functions upon
      strict abstention from alcohol, our data strongly support abstinence-oriented
      long-term treatment of alcoholics. The absence of functional recovery in patients
      with additional causes of brain damage might be explained by the 'dual hit'
      exhausting the regenerative potential of the HC.

PMID- 17179162
TI  - Health reform interrupted: the unraveling of the Oregon Health Plan.
AB  - The Oregon Health Plan (OHP) has received national and international attention
      for rationing medical care based on explicit priorities. However, in recent years
      OHP has lost substantial enrollment and struggled to live up to its core
      principles. This paper explores what went wrong in OHP and the implications of
      Oregon's experience for state-led health reform.

PMID- 17179163
TI  - Do condoms cause rape and mayhem? The long-term effects of condoms in New South
      Wales' prisons.
AB  - BACKGROUND: Concerns raised by opponents to condom provision in prisons have not
      been objectively examined and the issue continues to be debated. The long-term
      effects of the introduction of condoms and dental dams into New South Wales (NSW)
      prisons in 1996 was examined, focusing on particular concerns raised by
      politicians, prison officers, prison nurses and prisoners. These groups were
      worried that (a) condoms would encourage prisoners to have sex, (b) condoms would
      lead to an increase in sexual assaults in prisons, (c) prisoners would use
      condoms to hide and store drugs and other contraband and (d) prisoners would use
      condoms as weapons. METHOD: Data sources included the NSW Inmate Health Survey
      (IHS) from 1996 and 2001 and official reports from the NSW Department of
      Corrective Services. The 1996 IHS involved 657 men and 132 women randomly
      selected from all prisons, with a 90% response rate. The 2001 survey involved 747
      men and 167 women inmates, with an 85% response rate. RESULTS: There was a
      decrease in reports of both consensual male-to-male sex and male sexual assaults
      5 years after the introduction of condoms into prisons in 1996. The contents of
      condom kits were often used for concealing contraband items and for other
      purposes, but this was not associated with an increase in drug injecting in
      prison. Only three incidents of a condom being used in assaults on prison
      officers were recorded between 1996 and 2005; none was serious. CONCLUSIONS:
      There exists no evidence of serious adverse consequences of distributing condoms
      and dental dams to prisoners in NSW. Condoms are an important public health
      measure in the fight against HIV and sexually transmitted diseases; they should
      be made freely available to prisoners as they are to other high-risk groups in
      the community.

PMID- 17179164
TI  - Refractive outcomes after primary intraocular lens implantation in infants.
AB  - BACKGROUND: Intraocular lens (IOL) implantation is becoming increasingly accepted
      as a primary procedure in infants. AIM: To evaluate the accuracy of IOL power
      calculation, the rate of myopic shift and the refractive outcome after primary
      IOL implantation in infants aged <12 months at the time of cataract surgery.
      METHOD: A retrospective case review of 25 patients (8 with bilateral cataracts
      and 17 with unilateral cataracts) who underwent cataract surgery with primary IOL
      implantation at <12 months of age. Outcomes measured were actual early
      postoperative refraction, lens power calculation error, myopic shift and
      refractive outcome. RESULTS: In 83% of cases, actual postoperative refraction was
      within 2 dioptres (D) of the target refraction. Lens power calculation error did
      not depend on axial length, age at surgery or target refraction. Mean (SD) myopic
      shift was 5.43 (3.7) D in the first 12 months after surgery, but was
      significantly greater when surgery was performed at <10 weeks of age. CONCLUSION:
      This study demonstrates that IOL power can be calculated with reasonable accuracy
      in infants using current formulas. Factors such as age at the time of surgery,
      axial length, whether surgery is unilateral or bilateral, and the presence of
      systemic pathologies do not seem to influence the accuracy of lens power
      calculation or myopic shift up to 36 months of age.

PMID- 17179165
TI  - Expression of p27(KIP1) and cyclin D1, and cell proliferation in human pterygium.
AB  - BACKGROUND: The pterygium is a growth onto the cornea of fibrovascular tissue
      that is continuous with the conjunctiva, whereas the mechanisms of cell
      proliferation in pterygium epithelium are unknown. AIM: To analyse the
      histopathology and the expression of cell cycle-related molecules in pterygium
      tissues. METHODS: Seven pterygia were surgically removed using the bare-sclera
      procedure, and three normal bulbar conjunctivas were also obtained. Formalin
      fixed, paraffin-wax-embedded tissues were analysed by immunohistochemistry with
      anti-p27(KIP1), cyclin D1 and Ki-67 antibodies. RESULTS: Conjunctival epithelium
      consisted of several layers of round cells with a few goblet cells. Nuclear
      immunoreactivity for p27(KIP1) was noted in many normal epithelial cells, where
      cyclin D1 and Ki-67-positive nuclei were intermingled. A variety of goblet cells
      were located in the superficial layer of the pterygium head as well as those of
      the body epithelia. Several pterygium epithelial cells were p27(KIP1) positive,
      whereas nuclear immunoreactivity for cyclin D1 and Ki-67 was detected in many
      epithelial cells. By contrast, immunoreactivity for p27(KIP1), cyclin D1 and Ki
      67 was hardly detected in the pterygium stroma. CONCLUSION: It is suggested that
      pterygium growth and development are associated with the proliferation of
      epithelium, which is possibly involved in the expression of cell cycle-related
      molecules.

PMID- 17179166
TI  - Antipermeability and antiproliferative effects of standard and frozen bevacizumab
      on choroidal endothelial cells.
AB  - BACKGROUND: Bevacizumab is an antiangiogenic compound developed to target tumour
      vessels. Its off-label use in ophthalmology requires in vitro testing on ocular
      cells. AIM: To quantify the antipermeability and antiproliferative effects of
      bevacizumab on cultured choroidal endothelial cells (CECs). It was examined
      whether deep-freezing of bevacizumab attenuates its antiangiogenic activity.
      METHODS: Porcine CECs were cultured in permeable insert systems. Permeability of
      the cell monolayers was quantified by a fluorescent isothiocyanate-dextran assay
      after treatment with vascular endothelial growth factor (VEGF; 20-100 ng/ml)
      alone and in combination with bevacizumab (0.1-1 mg/ml). Proliferation of the
      CECs was tested using a "wound scratch" assay. The experiments were repeated with
      bevacizumab after freezing at -20 degrees C for 5 days. RESULTS: Bevacizumab
      significantly reduced VEGF-induced permeability in a dose-dependant manner. A
      molar ratio of 2.6:1 of bevacizumab to VEGF was required for complete blocking of
      VEGF-induced rise in permeability. CEC proliferation was significantly blocked by
      bevacizumab (0.5 mg/ml). Thawed bevacizumab after deep freezing showed a
      moderate, but not statistically significant loss in activity. CONCLUSION:
      Bevacizumab significantly reduces VEGF-induced permeability and proliferation of
      CECs. Freezing and thawing of bevacizumab will affect its biological activity.

PMID- 17179167
TI  - Human papillomavirus and pterygium. Is the virus a risk factor?
AB  - BACKGROUND: Pterygium is a disease of unknown origin and pathogenesis that might
      be vision threatening. It is characterised by a wing-like conjunctival overgrowth
      of the cornea. Several studies have investigated human papillomavirus (HPV) as a
      risk factor for the development of pterygia, but the results are inconclusive.
      AIM: To investigate a large sample of pterygia for the presence of HPV in order
      to clarify the putative association between pterygia and HPV. METHODS: 100
      specimens of pterygium from Danish patients and 20 normal conjunctival biopsy
      specimens were investigated for the presence of HPV with PCR technique using beta
      globin primers to access the quality of the extracted DNA and the HPV primers
      MY09/11 and GP5+/6+. HPV-positive specimens underwent subsequent HPV typing with
      type-specific HPV primers and further investigation with DNA in situ
      hybridisation (ISH). RESULTS: 90 of 100 investigated pterygia proved suitable for
      HPV analysis by PCR. As beta-globin could not be amplified, 10 specimens were
      excluded from the study. 4 of 90 pterygia harboured HPV. HPV type 6 was
      identified in all four HPV-positive pterygia. The 20 normal conjunctival biopsy
      specimens were beta-globin positive and HPV negative. All four pterygia that were
      HPV type 6 positive were DNA ISH negative. CONCLUSIONS: The low presence of HPV
      DNA in pterygia does not support the hypothesis that HPV is involved in the
      development of pterygia in Denmark.

PMID- 17179169
TI  - Efficient introduction of a bisecting GlcNAc residue in tobacco N-glycans by
      expression of the gene encoding human N-acetylglucosaminyltransferase III.
AB  - In this study, we show that introduction of human N-acetylglucosaminyltransferase
      (GnT)-III gene into tobacco plants leads to highly efficient synthesis of
      bisected N-glycans. Enzymatically released N-glycans from leaf glycoproteins of
      wild-type and transgenic GnT-III plants were profiled by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in native
      form. After labeling with 2-aminobenzamide, profiling was performed using normal
      phase high-performance liquid chromatography with fluorescence detection, and
      glycans were structurally characterized by MALDI-TOF/TOF-MS and reverse-phase
      nano-liquid chromatography-MS/MS. These analyses revealed that most of the
      complex-type N-glycans in the plants expressing GnT-III were bisected and carried
      at least two terminal N-acetylglucosamine (GlcNAc) residues in contrast to wild
      type plants, where a considerable proportion of N-glycans did not contain GlcNAc
      residues at the nonreducing end. Moreover, we have shown that the majority of N
      glycans of an antibody produced in a plant expressing GnT-III is also bisected.
      This might improve the efficacy of therapeutic antibodies produced in this type
      of transgenic plant.

PMID- 17179168
TI  - Inhibition of experimental corneal neovascularisation by bevacizumab (Avastin).
AB  - AIM: To evaluate the effect of topically administered bevacizumab (Avastin) on
      experimental corneal neovascularisation in rats. METHODS: Silver nitrate sticks
      (75% silver nitrate, 25% potassium nitrate) were used to perform chemical
      cauterisation on the corneas of 16 eyes from 16 male Long Evans rats. For the
      following 7 days, the 10 eyes in the treatment group were instilled with
      bevacizumab 4 mg/ml drops twice daily, whereas the 6 eyes in the control group
      received placebo (normal saline drops twice daily). Digital photographs of the
      cornea were analysed to determine the area of cornea covered by
      neovascularisation as a percentage of the total corneal area. RESULTS: In the
      bevacizumab-treated eyes, neovascularisation covered, on average, 38.2% (15.5%)
      (mean (SD)) of the corneal surface compared with 63.5% (5.0%) in the control
      group (p<0.02, Mann-Whitney U test). CONCLUSION: Topically administered
      bevacizumab (Avastin) at a concentration of 4 mg/ml limits corneal
      neovascularisation following chemical injury in the male Long Evans rat model.

PMID- 17179170
TI  - The distribution of net benefits under the National Health Insurance programme in
      Taiwan.
AB  - The redistributive effects of a social insurance programme are determined by how
      the programme is paid for-who pays and how much do they pay?-and how the benefits
      are distributed. As a result, the redistributive effects of a social health
      insurance programme should be evaluated on the basis of its net benefit-the
      difference between benefits and payment. Among the rich body of empirical
      analysis on equity in health care financing, however, most studies have relied on
      partial analysis, assessing equity by source of financing while ignoring the
      benefit side, or looking at equity in benefits but ignoring the funding side.
      Either approach risks misleading findings. In this study, therefore, the primary
      objective was to assess the distribution of net benefits across income groups
      under Taiwan's National Health Insurance (NHI) programme. This study observed a
      nationally representative sample of 74 012 NHI enrolees from 1996 to 2000. The
      unique NHI databases in Taiwan provide comprehensive enrolment and utilization
      information, and allowed linkage to each enrolee's income tax files. In addition
      to crude estimates, two-part models and ordinary least-square models were used to
      adjust inpatient and outpatient benefits for health care needs (age, sex, major
      disease status and physical disability). After adjusting for health care needs,
      the distribution of net benefits showed an apparent pro-poor pattern, with the
      lowest income group receiving the highest net benefits (NT$3353) and the top
      income group receiving the lowest net benefits (-NT$3072) in 1996. Although a
      clear pro-poor pattern was observed among those enrolees who paid wage-based
      premiums, this vertically equitable pattern was less evident among the enrolees
      who paid fixed premiums. Overall, a trend of increasing net benefits was observed
      in all income groups between 1996 and 2000, and all the NHI enrolees can be
      considered better off over time. In addition to contributing to the limited
      literature on equity in net benefits, the study provides an important policy
      reference to developing countries with large underground economies and relatively
      small populations of regular wage-earners as it indicates that using fixed
      premiums as a major financing scheme may pose a serious equity concern and policy
      challenge.

PMID- 17179171
TI  - Cardiac death in a patient with adult-onset Still's disease treated with the
      interleukin 1 receptor inhibitor anakinra.

PMID- 17179172
TI  - FCRL3 promoter 169 CC homozygosity is associated with susceptibility to
      rheumatoid arthritis in Dutch Caucasians.
AB  - BACKGROUND: Human leucocyte antigen is the only genetic risk factor for
      rheumatoid arthritis (RA) that has been consistently observed in different
      populations. A number of other genes such as PTPN22 and PADI4 showed population
      specific association with RA susceptibility. Recently, Fc receptor-like 3 (FCRL3)
      gene was found to be associated with RA susceptibility in Japanese, but with
      conflicting results in other populations. OBJECTIVE: To investigate the
      association of FCRL3 polymorphism with RA susceptibility and severity in Dutch
      Caucasian patients with RA, as well as to perform a meta-analysis to reveal the
      contribution of this gene to RA susceptibility. METHODS: A total of 931 Dutch RA
      cases and 570 unrelated Dutch controls were genotyped for four FCRL3 single
      nucleotide polymorphisms (SNPs). Genotyping was performed using the MassArray
      matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry.
      Association of the FCRL3 SNPs with susceptibility to RA was examined by single
      marker, carrier and haplotype analysis. RESULTS: Carrier analysis of the SNP
      (rs7528684) revealed the association of CC genotype with a higher risk of
      developing RA as compared with TT and TC carriers (p = 0.039 and OR = 1.31).
      There was no significant difference in the genotype and allele frequencies of all
      investigated SNPs between cases and controls. Meta-analysis of all studies
      comparing 9467 individuals showed that the OR for the CC genotype to develop RA
      was 1.2 and the p value <0.001. CONCLUSION: A promoter polymorphism of FCRL3
      (rs7528684) is associated with an increased risk of developing RA in Dutch
      Caucasians, suggesting that this association is relevant for RA in both Japanese
      and Caucasian populations.

PMID- 17179173
TI  - Inhibition of interleukin 1-induced matrix metalloproteinase 13 expression in
      human chondrocytes by interferon gamma.
AB  - BACKGROUND: Despite well-documented immunomodulation by interferon gamma
      (IFNgamma), its role and mechanism of regulation of matrix metalloproteinase 13
      (MMP13) gene expression in human chondrocytes is unknown. OBJECTIVE: To
      investigate the ability and mechanism of IFNgamma to suppress interleukin 1 (IL1)
      induced MMP13 expression in articular chondrocytes. METHODS: Human chondrocytes
      were treated with IFNgamma or IL1beta alone or in combination. MMP13 mRNA was
      analysed by semiquantitative reverse transcriptase-PCR. MMP13 protein, phospho
      signal transducer and activator of transcription 1 (STAT1) and p44/42 mitogen
      activated protein kinase levels were measured by western blotting. MMP13 promoter
      luciferase, cytomegalovirus cyclic AMP response element-binding protein
      (CBP)/p300 plasmids and STAT1 small interfering RNA (siRNA) were transfected by
      the calcium phosphate method. IFNgamma receptor was also neutralised. Activator
      protein (AP) 1 activity was monitored by the TransAM transcription factor kit.
      STAT1-CBP/p300 interaction was studied by immunoprecipitation. RESULTS: IFNgamma
      potently suppressed IL1-induced expression of MMP13 and promoter activity.
      Blockade with neutralising IFNgamma R1 antibody revealed that MMP13 inhibition by
      IFNgamma is mediated by the IFN receptor. IFNgamma-stimulated activation of STAT1
      was directly correlated with MMP13 suppression. Knockdown of the STAT1 gene by
      specific siRNA or its inhibition with fludarabine partially restored the IL1beta
      induction of MMP13 expression and promoter activity. IFNgamma did not alter AP1
      binding ability but promoted physical interaction of STAT1 and CBP/p300
      coactivator. p300 overexpression reversed IFNgamma inhibition of endogenous MMP13
      mRNA expression and exogenous MMP13 promoter activity. CONCLUSION: IFNgamma,
      through its receptor, activates STAT1, which binds with CBP/p300 coactivator,
      sequesters it from the cell system, and thus inhibits transcriptional induction
      of the MMP13 gene in chondrocytes. IFNgamma and its signalling pathways could be
      targeted therapeutically for diminishing IL1-induced cartilage degradation by
      MMP13 in patients with arthritis.

PMID- 17179174
TI  - Reversal of Sjogren's-like syndrome in non-obese diabetic mice.
AB  - BACKGROUND: Non-obese diabetic (NOD) mice exhibit autoimmune diabetes and
      Sjogren's-like syndrome. OBJECTIVE: To test whether a treatment that reverses end
      stage diabetes in the NOD mouse would affect their Sjogren's-like syndrome.
      METHODS: NOD mice have a proteasome defect. Improperly selected naive T cells
      escape, but can be killed by reintroducing major histocompatibility complex class
      I self-peptides on matched normal splenocytes. The proteasome defect also impairs
      nuclear factor kB, a transcription factor in pathogenic memory T cells,
      increasing their susceptibility to tumour necrosis factor-induced apoptosis
      stimulated through complete Freund's adjuvant (CFA). The impact of this two-limb
      therapy (injections of matched normal splenocytes and CFA) on the autoimmune
      salivary gland disease of the NOD mice was studied. RESULTS: All NOD mice
      receiving the above treatment had a complete recovery of salivary flow and were
      protected from diabetes. Restoration of salivary flow could be the result of a
      combination of rescue and regeneration of the gland, as confirmed by
      immunohistochemical analysis. All untreated NOD mice showed a continuous decline
      in salivary flow, followed by hyperglycaemia and death. CONCLUSION: This study
      establishes that a brief intervention in NOD mice with Sjogren's-like syndrome
      can reverse salivary gland dysfunction.

PMID- 17179175
TI  - Induction of remission in active anti-neutrophil cytoplasmic antibody-associated
      vasculitis with mycophenolate mofetil in patients who cannot be treated with
      cyclophosphamide.
AB  - BACKGROUND: Active anti-neutrophil cytoplasmic antibody-associated vasculitis
      (AAV) is commonly treated with cyclophosphamide, a drug with serious side
      effects, and with corticosteroids. OBJECTIVE: To determine the efficacy of a
      possible alternative drug for cyclophosphamide, oral mycophenolate mofetil (MMF)
      1000 mg twice daily and oral prednisolone 1 mg/kg once daily as remission
      induction treatment. METHODS: 32 consecutive patients with 34 episodes of active
      vasculitis who could not be treated with cyclophosphamide were diagnosed for a
      median (range) of 6.0 (0.3-22) years and experienced 4 (0-14) relapses prior to
      the current episode. Treatment response and relapse-free survival were analysed.
      RESULTS: Complete remission (CR) was obtained in 25 (78%) patients, partial
      remission (PR) in 6 (19%), whereas 1 (3%) patient did not respond. 19 patients
      relapsed, 13 (52%) after CR, 14 (3-58) months after starting the treatment and 6
      (100%) after PR, 6 (2-10) months after starting the treatment. The median relapse
      free survival was 16 months, comparable with the interval between the previous
      relapse and the current MMF-treated relapse (17 (3-134) months). Relapse-free
      survival at 1, 3, and 5 years was 63%, 38% and 27%, respectively. Patients who
      had been treated successfully with cyclophosphamide before responded better (CR
      84%, relapse 50%) than those who had not (CR 50%, relapse 100%). Minor
      gastrointestinal side effects and infections occurred frequently. MMF was
      prematurely discontinued due to adverse effects in two patients. CONCLUSION: MMF,
      in combination with prednisolone, can induce remission in patients with relapses
      of AAV intolerant to cyclophosphamide.

PMID- 17179176
TI  - Prediction of major clinical response (ACR50) to infliximab in psoriatic
      arthritis refractory to methotrexate.
AB  - OBJECTIVES: To determine the predictive factors of clinical response to
      infliximab in patients with refractory psoriatic polyarthritis. METHODS: A
      multicentre open study which included 69 patients with psoriatic polyarthritis
      refractory to methotrexate (15 mg/week at least for 8 weeks). Patients were
      treated with infliximab 5 mg/kg every 8 weeks in addition to their stable doses
      of methotrexate. A major clinical response was defined by the ACR50 at week 38.
      Logistic regression analysis was performed to analyse which of the following
      measures at the start of treatment were associated with an ACR50 response:
      demographic and clinical characteristics, duration of disease, tender and swollen
      joint counts, involvement of large joints (knee or hip, or both), erythrocyte
      sedimentation rate, C reactive protein (CRP), Health Assessment Questionnaire
      disability index, axial involvement, and the presence of erosions at baseline.
      RESULTS: In an intention to treat analysis 30/69 (44%) patients achieved an ACR50
      response. In the univariate analysis both the presence of large joint involvement
      and severe disability were associated with a poor clinical response. In a
      multivariate logistic regression analysis high CRP values were independently
      associated with a good therapeutic response (odds ratio (OR)=18.7; 95% confidence
      interval (CI) 1.8 to 181.6; p=0.011). In contrast, large joint involvement and
      severe disability were associated with a poor response, which reached
      significance for large joint involvement (OR=29.3; 95% CI 3.2 to 266.3; p=0.003).
      CONCLUSION: A lower disability and, in particular, the absence of large joint
      involvement and higher CRP serum levels at the start of infliximab treatment are
      factors that seem to influence the probability of achieving a good therapeutic
      response in patients with psoriatic arthritis.

PMID- 17179177
TI  - High sensitivity RNA pseudoknot prediction.
AB  - Most ab initio pseudoknot predicting methods provide very few folding scenarios
      for a given RNA sequence and have low sensitivities. RNA researchers, in many
      cases, would rather sacrifice the specificity for a much higher sensitivity for
      pseudoknot detection. In this study, we introduce the Pseudoknot Local Motif
      Model and Dynamic Partner Sequence Stacking (PLMM_DPSS) algorithm which predicts
      all PLM model pseudoknots within an RNA sequence in a neighboring-region
      interference-free fashion. The PLM model is derived from the existing Pseudobase
      entries. The innovative DPSS approach calculates the optimally lowest stacking
      energy between two partner sequences. Combined with the Mfold, PLMM_DPSS can also
      be used in predicting complicated pseudoknots. The test results of PLMM_DPSS,
      PKNOTS, iterated loop matching, pknotsRG and HotKnots with Pseudobase sequences
      have shown that PLMM_DPSS is the most sensitive among the five methods. PLMM_DPSS
      also provides manageable pseudoknot folding scenarios for further structure
      determination.

PMID- 17179178
TI  - Functional organization of the Rpb5 subunit shared by the three yeast RNA
      polymerases.
AB  - Rpb5, a subunit shared by the three yeast RNA polymerases, combines a eukaryotic
      N-terminal module with a globular C-end conserved in all non-bacterial enzymes.
      Conditional and lethal mutants of the moderately conserved eukaryotic module
      showed that its large N-terminal helix and a short motif at the end of the module
      are critical in vivo. Lethal or conditional mutants of the C-terminal globe
      altered the binding of Rpb5 to Rpb1-beta25/26 (prolonging the Bridge helix) and
      Rpb1-alpha44/47 (ahead of the Switch 1 loop and binding Rpb5 in a two-hybrid
      assay). The large intervening segment of Rpb1 is held across the DNA Cleft by
      Rpb9, consistent with the synergy observed for rpb5 mutants and rpb9Delta or its
      RNA polymerase I rpa12Delta counterpart. Rpb1-beta25/26, Rpb1-alpha44/45 and the
      Switch 1 loop were only found in Rpb5-containing polymerases, but the Bridge and
      Rpb1-alpha46/47 helix bundle were universally conserved. We conclude that the
      main function of the dual Rpb5-Rpb1 binding and the Rpb9-Rpb1 interaction is to
      hold the Bridge helix, the Rpb1-alpha44/47 helix bundle and the Switch 1 loop
      into a closely packed DNA-binding fold around the transcription bubble, in an
      organization shared by the two other nuclear RNA polymerases and by the archaeal
      and viral enzymes.

PMID- 17179179
TI  - Histone acetylation-independent transcription stimulation by a histone chaperone.
AB  - Histone chaperones are thought to be important for maintaining the physiological
      activity of histones; however, their exact roles are not fully understood. The
      physiological function of template activating factor (TAF)-I, one of the histone
      chaperones, also remains unclear; however, its biochemical properties have been
      well studied. By performing microarray analyses, we found that TAF-I stimulates
      the transcription of a sub-set of genes. The transcription of endogenous genes
      that was up-regulated by TAF-I was found to be additively stimulated by histone
      acetylation. On performing an experiment with a cell line containing a model gene
      integrated into the chromosome, TAF-I was found to stimulate the model gene
      transcription in a histone chaperone activity-dependent manner additively with
      histone acetylation. TAF-I bound to the core histones and remodeled the chromatin
      structure independent of the N-terminal histone tail and its acetylation level in
      vitro. These results suggest that TAF-I remodel the chromatin structure through
      its interaction with the core domain of the histones, including the histone fold,
      and this mechanism is independent of the histone acetylation status.

PMID- 17179180
TI  - The bidirectional promoter of two genes for the mitochondrial translational
      apparatus in mouse is regulated by an array of CCAAT boxes interacting with the
      transcription factor NF-Y.
AB  - The genes for mitoribosomal protein S12 (Mrps12) and mitochondrial seryl-tRNA
      ligase (Sarsm and Sars2) are oppositely transcribed from a conserved promoter
      region of <200 bp in both human and mouse. Using a dual reporter vector we
      identified an array of 4 CCAAT box elements required for efficient transcription
      of the two genes in cultured mouse 3T3 cells, and for enforcing directionality in
      favour of Mrps12. Electrophoretic mobility shift assay (EMSA) and in vivo
      footprinting confirmed the importance of these promoter elements as sites of
      protein-binding, and EMSA supershift and chromatin immunoprecipitation (ChIP)
      assays identified NF-Y as the key transcription factor involved, revealing a
      common pattern of protein-DNA interactions in all tissues tested (liver, brain,
      heart, kidney and 3T3 cells). The inherently bidirectional activity of NF-Y makes
      it an especially suitable factor to govern promoters of this class, whose
      expression is linked to cell proliferation.

PMID- 17179181
TI  - Decrease of cholesterol in mouse melanoma causes secretion of lysosomal enzymes.
AB  - We examined the change in the subcellular distribution of a lysosomal enzyme,
      beta-glucuronidase (beta-G), caused by decreased cholesterol levels in mouse
      melanoma cells using an HMG-CoA reductase inhibitor, lovastatin and lipoprotein
      deficient serum (LDS). There was a decrease in the cholesterol content of the
      cells and increased secretion of the mature form of beta-G located in lysosomes,
      as documented by Percoll density gradient fractionation, digitonin
      permeabilization and immunoprecipitation. Furthermore, another lysosomal enzyme,
      cathepsin H, was found to be released in the medium from cells treated with
      lovastatin. Both the precursor and mature forms of cathepsin H were detected in
      the medium of treated cells. Next, when cells were treated with LDS without
      lovastatin, concomitantly with the decrease in the levels of cholesterol and beta
      G activity in the cells, beta-G activity in the medium increased. Also, the ratio
      of beta-G (3.2-fold) released in the medium from cells treated with Dulbecco's
      modified Eagle medium (D-MEM) containing lovastatin and LDS was higher than that
      (2.3-fold) on treatment with D-MEM containing LDS without lovastatin. From these
      results, it was suggested that the exocytosis of mature enzymes from lysosomes
      into the medium or mis-sorting of the lysosomal precursor forms to the medium was
      caused by the lovastatin- and/or LDS-induced decrease in the cholesterol content
      of the cells, although the mechanism of secretion by lysosomal enzymes differed
      somewhat.

PMID- 17179182
TI  - Discrimination of early and late apoptotic cells by NBD-phosphatidylserine
      labelling and time-lapse observation of phagocytosis of apoptotic cells by
      macrophages.
AB  - Since free apoptotic cells are not detected in normal tissues, it is generally
      believed that apoptotic cells are removed as soon as they appear in vivo. A
      fluorescent derivative of phosphatidylserine, 1-palmitoyl-2-[6-[(7-nitro-2-1,3
      benzoxadiazol-4-yl)amino]hexanoyl]-sn-glycero-3-phospho-L-serine (NBD-PS) is
      known to be incorporated into living cells, and thereafter gradually absorbed
      into either fatty acid-free bovine serum albumin or fetal calf serum from the
      outer leaflet of the cell membrane. When thymocytes were irradiated with X-ray
      and cultured in the presence of NBD-PS, cells became less fluorescent as
      apoptosis advanced, but early apoptotic cells were still positive for NBD-PS. We
      then co-cultured such early apoptotic thymocytes with resident peritoneal
      macrophages. Upon examination under a time-lapse fluorescence microscope, it was
      found that the attachment of early apoptotic cells to macrophages does not cause
      rapid phagocytosis, as compared with late apoptotic cells, suggesting the
      possibility that, in contrast to the widely held view, early apoptotic cells may
      not be quickly removed by phagocytes in vivo.

PMID- 17179184
TI  - Perianth bottom-specific blue color development in Tulip cv. Murasakizuisho
      requires ferric ions.
AB  - The entire flower of Tulipa gesneriana cv. Murasakizuisho is purple, except the
      bottom, which is blue. To elucidate the mechanism of the different color
      development in the same petal, we prepared protoplasts from the purple and blue
      epidermal regions and measured the flavonoid composition by HPLC, the vacuolar pH
      by a proton-selective microelectrode, and element contents by the inductively
      coupled plasma (ICP) method. Chemical analyses revealed that the anthocyanin and
      flavonol compositions in both purple and blue colored protoplasts were the same;
      delphinidin 3-O-rutinoside (1) and major three flavonol glycosides, manghaslin
      (2), rutin (3) and mauritianin (4). The vacuolar pH values of the purple and blue
      protoplasts were 5.5 and 5.6, respectively, without any significant difference.
      However, the Fe(3+) content in the blue protoplast was approximately 9.5 mM,
      which was 25 times higher than that in the purple protoplasts. We could reproduce
      the purple solution by mixing 1 with two equimolar concentrations of flavonol
      with lambda(vismax) = 539 nm, which was identical to that of the purple
      protoplasts. Furthermore, addition of Fe(3+) to the mixture of 1-4 gave the blue
      solution with lambda(vismax) = 615 nm identical to that of the blue protoplasts.
      We have established that Fe(3+) is essential for blue color development in the
      tulip.

PMID- 17179183
TI  - W323S variant of Xiap-Bir3 binds to SMAC but not caspase-9.
AB  - The ability of the wild-type XIAP BIR3 domain as well as its Trp323Ser variant in
      inhibition of human caspase-9, binding to AVPFVASLPN (SMAC-peptide), SMAC
      protein, and mature caspase-9 was investigated. In order to investigate the role
      of W323 on these interactions, this residue was mutated to Serine. Circular
      dichroism as well as thermal denaturation studies showed that W323S mutation did
      not hamper proper folding of the protein. The dissociation constants for the
      interaction of the wild type BIR3 as well as its mutant to Smac-type peptide were
      found to be 1.8 and 27 muM, respectively. The inhibition of and binding to
      caspase-9 by wild-type BIR3 and its mutant were also compared. While the wild
      type protein potently inhibited the enzyme, the mutant failed to do so. The lack
      of caspase-9 inhibition was due to absence of interaction of the mutant BIR3 with
      mature caspase-9. These results indicate that Trp323 of BIR3 plays a pivotal role
      both in maintaining necessary conformation for caspase-9 interaction and to a
      lesser extent, recognition of Smac-type peptide. Moreover, decreased stability of
      the mutant compared with the wild type indicates that W323 is essential for
      maintaining the stability BIR3-Smac-peptide complex.

PMID- 17179186
TI  - Concerning: generic outpatient referrals.

PMID- 17179185
TI  - Prediction of glomerular filtration rate decline in diabetic subjects with
      impaired renal function.

PMID- 17179187
TI  - Choroidal detachment associated with latanoprost use in the fellow eye.

PMID- 17179189
TI  - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in
      hypertension due to primary aldosteronism: a case for exclusion.
AB  - Aldosterone antagonists are the mainstay of therapy in patients with hypertension
      due to primary aldosteronism. However, in our experience, these patients are
      sometimes placed on angiotensin-converting enzyme (ACE) inhibitors in accordance
      with guidelines applying to the general hypertensive population. We believe this
      practice is inappropriate because of the inability of ACE inhibitors to lower
      blood pressure in patients with low renin levels. Furthermore, pleiotropic
      effects of ACE inhibitors are unlikely to provide significant benefits in the
      absence of blood pressure reduction. Therefore, ACE inhibitors should be
      discouraged for the majority of patients with primary aldosteronism, even in the
      face of renal or cardiac disease.

PMID- 17179188
TI  - Short-term hemostatic safety of strontium ranelate treatment in elderly women
      with osteoporosis.
AB  - BACKGROUND: Strontium ranelate offers significant clinical benefits in terms of
      efficacy, tolerability, and ease of administration in the treatment of
      postmenopausal osteoporosis. However, there are some data revealing an
      association between strontium ranelate treatment and increased incidence of
      venous thromboembolism (VTE), suggesting possible adverse prothrombotic effects
      of the drug. OBJECTIVE: To assess the effect of strontium ranelate treatment on
      primary hemostasis, secondary hemostasis, and the natural anticoagulant defense
      system, together with prothrombotic markers, in elderly women with osteoporosis.
      METHODS: This study was designed in a prospective manner. Thirty-five elderly
      women diagnosed with osteoporosis were included. During a 2 month treatment
      period, participants received strontium ranelate 2 g. Platelet Function Analyzer
      100 (PFA-100) in vitro bleeding time was performed to depict primary hemostasis.
      Secondary hemostatic parameters including prothrombin time, international
      normalized ratio, activated partial thromboplastin time, anti-cardiolipine
      immunoglobulin (Ig) M and IgG, antiphospholipid IgM and IgG, protein C, protein
      S, antithrombin III, lupus anticoagulant, fibrinogen, thrombin, activated protein
      C resistance, and plasma levels of d-dimer were assessed. These parameters were
      tested before and after 2 month treatment with strontium ranelate. RESULTS: Mean
      +/- SD age of the patients was 72.82 +/- 5.69 years. After 60 days of treatment,
      there was no statistically significant prolongation in PFA-100 in vitro bleeding
      time and no statistically significant change in the critical hemostatic
      parameters in patients receiving strontium ranelate that led to discontinuation
      of the treatment. None of the subjects developed clinical VTE during the 2 month
      period of strontium ranelate treatment. CONCLUSIONS: The hemostatic safety of
      strontium ranelate in the elderly population with osteoporosis was shown over 2
      months of treatment; however, its long-term hemostatic safety should be evaluated
      further.

PMID- 17179190
TI  - Psoriasis following growth hormone therapy in a child.
AB  - OBJECTIVE: To report a case of psoriasis that developed following growth hormone
      treatment. CASE SUMMARY: An 8-year-old boy was admitted to our pediatric
      endocrinology department because of short stature (<3rd percentile). A dopamine
      stimulation test and an insulin tolerance test revealed growth hormone (GH)
      deficiency with a normal cortisol response. His insulin-like growth factor 1 (IGF
      1) level (9 ng/mL; reference range 113-261) was under the limits for his age and
      sex. Six months after the initiation of treatment with recombinant human GH 0.33
      mg/kg/wk, the patient presented with a 10 day history of desquamation and a
      burning sensation in his right knee and hip. Lesions of erythematous papules
      consistent with plaques of psoriasis were present. Histologic findings from skin
      biopsies were consistent with psoriasis. The GH dose was reduced to 0.2 mg/kg/wk
      and treatment for psoriasis (including hydrocortisone and clemastine) was
      started. Three months after those interventions, the plaques had resolved.
      DISCUSSION: Previous studies proposed that the extent and severity of psoriasis
      correlate with GH levels, although psoriatic patients, in general, have normal GH
      and IGF-1 levels. The Naranjo probability scale indicated that the development of
      psoriasis was probably associated with GH therapy. CONCLUSIONS: This case
      suggests that the development of psoriasiform lesions in a previously unaffected
      individual represents an adverse effect of GH treatment, occurring at higher
      doses, with higher IGF-1 levels.

PMID- 17179191
TI  - Pharmacist influence in buprenorphine treatment outcomes for opioid dependence.

PMID- 17179192
TI  - Multiple endocrine neoplasia type 1 (MEN1): loss of one MEN1 allele in tumors and
      monohormonal endocrine cell clusters but not in islet hyperplasia of the
      pancreas.
AB  - CONTEXT: The occurrence of multiple small pancreatic endocrine tumors in patients
      suffering from multiple endocrine neoplasia type 1 (MEN1) represents a unique
      possibility to study early neoplasms and their potential precursor lesions. To
      date, it is unknown whether small islet-like endocrine cell clusters found in
      MEN1 patients are neoplastic or rather hyperplastic. It is also unclear whether
      microadenomas develop from islets. DESIGN: We hypothesized that monohormonal
      endocrine cell clusters observed in MEN1 patients are small neoplasms with loss
      of heterozygosity of the MEN1 locus. Using a technique combining fluorescence in
      situ hybridization of the MEN1 locus and the centromeric region of chromosome 11q
      with hormone immunostaining, we examined resection specimens from four MEN1
      patients. We focused our investigations on the following: 1) typical
      microadenomas; 2) monohormonal endocrine cell clusters; 3) endocrine and exocrine
      structures entrapped in microadenomas; and 4) morphologically normal islets.
      RESULTS: Loss of one MEN1 allele was found in all 27 microadenomas and 19 of 20
      (95%) monohormonal endocrine cell clusters. By contrast, it was absent in islets
      and ductal or acinar structures. Our results indicate that monohormonal endocrine
      cell clusters represent a minute form of microadenomas. CONCLUSION: The frequent
      presence of single nonneoplastic insulin cells in microadenomas and the
      occurrence of microadenomas in islets suggest an islet origin of microadenomas.
      Islet hyperplasia does not seem to be an obligatory stage in pancreatic MEN1
      associated tumor development.

PMID- 17179193
TI  - Stage-specific expression of androgen receptor, follicle-stimulating hormone
      receptor, and anti-Mullerian hormone type II receptor in single, isolated, human
      preantral follicles: relevance to polycystic ovaries.
AB  - CONTEXT: Recent evidence indicates that the increase in follicle numbers seen in
      polycystic ovary syndrome occurs early in folliculogenesis, with androgens being
      a likely causative candidate. In primates and sheep, androgen excess in utero
      results in ovarian changes similar to those in polycystic ovary syndrome. There
      is also increasing interest in the role of anti-Mullerian hormone (AMH) in early
      folliculogenesis because AMH knockout mice have an early depletion of their stock
      of primordial follicles. Initiation and early folliculogenesis may therefore be
      under negative control by AMH and positive control by androgens. OBJECTIVE:
      Because AMH signals exclusively through its type II receptor (AMHRII), the aim of
      this study was to determine and colocalize the stage-specific expression of
      AMHRII, androgen receptor (AR), and FSH receptor (FSHR) mRNA in individual, well
      characterized preantral follicles. METHOD: Follicles were isolated from human
      ovarian cortex obtained from either oophorectomies or cortical biopsies at
      cesarean section. Expression of AR, FSHR, and AMHRII mRNA was determined using a
      nested RT-PCR protocol. RESULTS: AR mRNA was not detected in any primordial
      follicles but was from the transitional stage onward. The number of AR-positive
      follicles increased at each progressive growth stage. The expression of AR
      preceded that of FSHR, and only a small percentage of primary follicles expressed
      FSHR. AMHRII expression was rarely detected. CONCLUSIONS: This is the first study
      to identify the expression of AR in human transitional follicles. Results suggest
      a role for androgens in promoting early follicle growth and challenging the
      hypothesis that AMH exerts a direct, inhibitory effect on follicles at this
      stage.

PMID- 17179194
TI  - Stimulating and blocking thyroid-stimulating hormone (TSH) receptor
      autoantibodies from patients with Graves' disease and autoimmune hypothyroidism
      have very similar concentration, TSH receptor affinity, and binding sites.
AB  - OBJECTIVE: The distinct biological properties of TSH receptor (TSH-R)
      autoantibodies (TRAbs) from patients with Graves' disease (GD) are yet
      unexplained on the molecular level. Here we compare serum concentration, affinity
      to the TSH-R, and binding sites on the TSH-R of stimulating (TSAb) and blocking
      (TBAb) TRAbs. METHODS AND PATIENTS: Four-step affinity purification using human
      recombinant TSH-R was performed with 22 TRAb-positive sera from GD patients (11
      with only TSAb and 11 with only TBAb) and five control sera. Antibody
      concentration, TSH binding inhibition (TBII), and TSAb/TBAb activity of the
      purified TRAb were assessed. Labeled purified TRAbs were used for displacement
      studies with TRAb and an additional 30 patients and 10 control sera. RESULTS:
      TRAbs could be purified to 80-93% purity with recovery of the TBII and TSAb and
      TBAb activity. No TRAbs could be purified from healthy individuals. The mean +/-
      SD concentration of TRAb was 17.3 +/- 5.4 microg/IU for the TSAb sera (range, 9.6
      25.9) and 18.2 +/- 8.5 microg/IU for the TBAb sera (range, 4.6-29.2),
      respectively (P = 0.79). Affinity was in the picomolar range for both TRAb
      subtypes with mean +/- sd dissociation constant of 167 +/- 109 pM (60-410 pM) for
      TSAb and 253 +/- 132 pM (80-410 pM) for TBAb (P = 0.12). Purified and labeled
      TSAb and TBAb showed a very similar binding pattern to the TSH-R in displacement
      studies with unlabeled TSAb/TBAb or unpurified patients sera, indicating binding
      sites on the TSH-R in close proximity to each other. CONCLUSION: TSAbs and TBAbs
      in the serum of patients with GD have similar characteristics. They are of low
      concentration with high affinity and have also similar binding epitopes on the
      TSH-R.

PMID- 17179195
TI  - The relationship between smoking status and cortisol secretion.
AB  - CONTEXT: Evidence for an association of smoking status with cortisol secretion is
      mixed. OBJECTIVE: The objective of the study was to assess the relationship
      between smoking status and salivary cortisol. DESIGN: This was a cross-sectional
      study of smoking status and cortisol secretion from phase 7 (2002-2004) of the
      Whitehall II study. SETTING: An occupational cohort was originally recruited in
      1985-1987. PARTICIPANTS: The study population consisted of 3103 men (1514 never
      smokers, 1278 ex-smokers, and 311 smokers) and 1128 women (674 never-smokers, 347
      ex-smokers, and 107 smokers). Information was collected on smoking status,
      average number of cigarettes smoked, and additional covariates. OUTCOME MEASURES:
      Saliva samples were taken on waking; waking + 0.5, 2.5, 8, and 12 h; and bedtime
      for the assessment of cortisol. RESULTS: Smoking status was significantly
      associated with increased salivary cortisol release throughout the day (P <
      0.001) adjusted for covariates; this was apparent for the cortisol awakening
      response (P < 0.001) when examined separately. Compared with never-smokers,
      smokers had higher release of total cortisol (P = 0.002), whereas no difference
      was observed between never-smokers and ex-smokers (P = 0.594): mean release per
      hour (nanomoles per liter), never-smokers, 4.13 [confidence interval (CI) 4.02
      4.24]; ex-smokers, 4.21 (CI 4.08-4.35); smokers, 4.63 (CI 4.35-4.93). There was
      no significant relationship between number of cigarettes smoked and total
      cortisol release. However, a difference was observed for the cortisol awakening
      response: mean release by tertiles of cigarettes smoked (nanomoles per liter):
      high, 13.49 (CI 10.74-16.23); medium, 9.58 (CI 7.40-11.76); low, 8.49 (CI 5.99
      10.99), P = 0.029. CONCLUSION: Salivary cortisol is increased in current smokers,
      compared with nonsmokers; no differences were observed between ex-smokers and
      never-smokers, suggesting that smoking has a short-term effect on the
      neuroendocrine system.

PMID- 17179196
TI  - Possible association between diabetes and bisphosphonate-related jaw
      osteonecrosis.
AB  - CONTEXT: Bisphosphonate-related osteonecrosis (BON) of the jaws is a newly
      identified condition for which the exact mechanism involved in its pathogenesis
      remains obscure. OBJECTIVE: The objective of the study was to evaluate whether
      diabetes mellitus (DM) may be a contributing factor in the development of BON.
      DESIGN: From 2004 to 2006, 31 patients were diagnosed with BON. The diagnosis of
      BON was based on the medical and dental history of each patient as well as the
      observation of clinical signs and symptoms of this pathological process. DM was
      based on two consecutive fasting blood glucose levels above 7 mmol/liter.
      SETTING: The study was completed in the Hebrew University-Hadassah Hospital
      referral center. RESULTS: Of the 31 patients with BON, 18 (58%) were found to
      have DM or impaired fasting glucose. The proportion of diabetic patients was much
      higher than expected relative to the incidence of DM in the general population
      (14%) and compared with the proportion of diabetic patients in a control group of
      oncological patients treated with bisphosphonates and without BON (12%) (P =
      0.00003). CONCLUSIONS: This finding indicates that DM may be a risk factor for
      BON and that DM patients treated with bisphosphonates should be carefully
      monitored. We discuss here the bone metabolic pathways characteristic of DM
      patients and the way in which these pathways can augment the effects of
      bisphosphonates.

PMID- 17179197
TI  - Clinical review: Identifying children at risk for polycystic ovary syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) appears to arise as a complex trait
      with contributions from both heritable and nonheritable factors. Polygenic
      influences appear to account for about 70% of the variance in pathogenesis. In
      view of this evidence for congenital contributions to the syndrome, childhood
      manifestations may be expected. OBJECTIVE: The objective has been to review the
      evidence that risk factors for PCOS can be recognized in childhood. DESIGN: This
      study consisted of screening of the PCOS literature for articles pertaining to
      potential childhood and adolescent antecedents. RESULTS: Congenital virilizing
      disorders; above average or low birth weight for gestational age; premature
      adrenarche, particularly exaggerated adrenarche; atypical sexual precocity; or
      intractable obesity with acanthosis nigricans, metabolic syndrome, and pseudo
      Cushing syndrome or pseudo-acromegaly in early childhood have been identified as
      independent prepubertal risk factors for the development of PCOS. During
      adolescence, PCOS may masquerade as physiological adolescent anovulation.
      Asymptomatic adolescents with a polycystic ovary occasionally (8%) have
      subclinical PCOS but often (42%) have a subclinical PCOS type of ovarian
      dysfunction, the prognosis for which is unclear. CONCLUSION: Identifying children
      at risk for PCOS offers the prospect of eventually preventing some of the long
      term complications associated with this syndrome once our understanding of the
      basis of the disorder improves.

PMID- 17179199
TI  - Prediction of adult height in growth-hormone-treated children with growth hormone
      deficiency.
AB  - CONTEXT: Several studies have searched for factors that significantly influence
      adult height (AH) of children with GH deficiency (GHD) who have been treated with
      biosynthetic GH, but a prediction model for AH has not yet been presented.
      OBJECTIVE: Our objective was to develop models for prediction of AH, using
      information available at the start of GH treatment or after 1 yr of treatment.
      DESIGN AND SETTING: For this retrospective study, data were collected from the
      National Registry of Growth Hormone Treatment in Children, which contained data
      of Dutch children treated with GH. PATIENTS/INTERVENTION: Patients included males
      born before 1985 and females born before 1987 with either diagnosis of GHD
      (syndromes, tumors, and other diseases were excluded) or a maximal GH response
      during provocation tests of less than 11 ng/ml, treated with biosynthetic GH for
      at least 1 yr. To be able to use the complete group of 342 children for the
      development of the models, multiple imputation was used for missing values. MAIN
      OUTCOME MEASURE: We assessed AH sd scores (SDS). RESULTS: Each prediction model
      contained both target height SDS and current height SDS. The change in height SDS
      during the first year proved an important predictor for AH. In all models,
      addition of GH dose was not significant. The percent explained variance, after
      correction for overfitting, ranged from 37% (prepubertal children, prediction at
      start) to 60% (pubertal children, prediction after 1 yr). CONCLUSION: The
      presented prediction models give accurate predictions of AH for children with GHD
      at start and after 1 yr of GH treatment. They are useful tools in the treatment
      of these children.

PMID- 17179201
TI  - The 3D vascular status of the follicle after HCG administration is qualitatively
      rather than quantitatively associated with its reproductive competence.
AB  - BACKGROUND: The objective of this study was to determine whether the vascular
      status of a single pre-ovulatory follicle is associated quantitatively and/or
      qualitatively with its reproductive competence. METHODS: We studied 61
      monofollicular IVF-embryo transfer cycles. Just before single oocyte retrieval,
      follicle vascularization was detected by transvaginal power-Doppler, 3
      dimensionally reconstructed, and analysed quantitatively by coloured/gray voxel
      ratio [vascularization index (VI)] and qualitatively by blood cell displacement
      [flow index (FI)] calculation. Cycles were sorted in two sets of two groups: low
      VI (<or=8%, n = 44) and high VI (>8%, n = 17); low FI (<or=30, n = 22) and high
      FI (>30, n = 39). RESULTS: Patients' characteristics, fertilization rates, and
      embryo morphology were comparable in all groups. In contrast, clinical pregnancy
      rates/oocyte retrieval (4% versus 33%, P < 0.009) and implantation rates (11%
      versus 50%, P < 0.04) were markedly poorer in the low as compared to the high FI
      groups, respectively, but remained similar between the low and the high VI groups
      (22% versus 23% and 38% versus 44%, respectively). CONCLUSIONS: A qualitative
      (FI) rather than quantitative (VI) relationship exists between vascular status
      and functional quality of the follicle after HCG administration.

PMID- 17179198
TI  - Influence of serum leptin on weight and body fat growth in children at high risk
      for adult obesity.
AB  - OBJECTIVE: Our objective was to examine serum leptin prospectively as a predictor
      of weight and body fat growth in children at high risk for adult obesity. We
      hypothesized that leptin measurements would be positively associated with
      increased growth of adipose tissue because children with high baseline leptin for
      their body fat mass have greater leptin resistance and thus would have greater
      susceptibility to weight gain. METHODS: Children ages 6-12 yr at high risk for
      adult obesity because of early-onset childhood overweight and/or parental
      overweight were recruited from 1996-2004. Growth in body mass index (BMI) was
      studied in 197 children, and growth in total body fat mass was examined in 149
      children over an average follow-up interval of 4.4 yr (range, 1-8 yr).
      Longitudinal analyses accounted for sex, race, socioeconomic status, initial body
      composition, age, skeletal age, and physical activity and included all available
      interim visits for each individual so that a total of 982 subject visits were
      included in the analysis. RESULTS: At baseline, 43% of children studied were
      overweight (BMI > or = 95th percentile); during follow-up, an additional 14%
      became overweight. Independent of initial body composition, baseline leptin was a
      statistically significant positive predictor of increased BMI (P = 0.0147) and
      increased total body fat mass (P < 0.007). CONCLUSIONS: High serum leptin,
      independent of body fat, may be an indicator of increased leptin resistance,
      which predisposes children at high risk for adult obesity to somewhat greater
      growth in weight and body fat during childhood.

PMID- 17179200
TI  - Growth hormone therapy improves bone mineral density in children with cerebral
      palsy: a preliminary pilot study.
AB  - CONTEXT: Cerebral palsy is associated with osteopenia, increased fracture risk,
      short stature, and decreased muscle mass, whereas GH therapy is associated with
      increased bone mineral density (BMD) and linear growth and improvement in body
      composition. OBJECTIVE: We conducted a pilot study to evaluate the effect of 18
      months of GH therapy on spinal BMD, linear growth, biochemical markers, and
      functional measures in children with cerebral palsy. DESIGN AND SETTING: The
      study was a randomized control trial, conducted from 2002-2005 at the University
      of California, Los Angeles, Orthopedic Hospital's Center for Cerebral Palsy.
      PATIENTS: Patients included 12 males with cerebral palsy, ages 4.5-15.4 yr.
      INTERVENTION: We compared 18 months of GH (50 microg daily) vs. no treatment.
      PRIMARY OUTCOME MEASURES: Spinal BMD (dual-energy x-ray absorptiometry scan),
      height, growth factors, and bone markers were assessed. RESULTS: Ten subjects
      (five in each group) completed the study. Pre- and post-average height z-scores
      were -1.47 +/- 0.23 and 0.8 +/- 0.2 (GH-treated group) vs. -1.35 +/- 1.26 and 
      1.36 +/- 1.27 (control group) (Delta SD score, 0.67 vs. -0.01; P = 0.01). Average
      change in spinal BMD z-score (Delta SD score corrected for height) was 1.169 +/-
      0.614 vs. 0.24 +/- 0.25 in the treated and control groups, respectively (P =
      0.03). Osteocalcin, IGF-I, and IGF-binding protein 3 levels increased during GH
      therapy. There was no change in quality of life scores as measured by the
      Pediatric Orthopedic Disability Inventory. CONCLUSIONS: This small pilot study
      suggests that 18 months of GH therapy is associated with statistically
      significant improvement in spinal BMD and linear growth.

PMID- 17179202
TI  - A B23-interacting sequence as a tool to visualize protein interactions in a
      cellular context.
AB  - We report the characterization of a nucleolar localization sequence (NoLS) that
      targets the green fluorescent protein (GFP) into the granular component (GC) of
      nucleoli. This NoLS interacts in vitro specifically and directly with the major
      nucleolar protein B23 and more precisely with the region of B23 including the two
      acidic stretches. The affinity of NoLS for B23 is stronger than that of the HIV-1
      Rev protein in vitro. Moreover, B23-NoLS interaction also occurs in vivo. Indeed,
      (1) NoLS confers on the GFP the behavior of B23 throughout the cell cycle, (2)
      the GFP-NoLS fusion and B23 remain colocalized after drug treatments, (3) a
      selective delocalization of B23 from nucleoli to nucleoplasm induces a
      concomitent delocalization of the GFP-NoLS fusion, and (4) the fusion of NoLS to
      fibrillarin makes it possible to colocalize fibrillarin and B23. Interestingly,
      by fusing NoLS to fibrillarin, both fibrillarin and the fibrillarin partner Nop56
      are mislocalized in the GC of nucleoli. Similarly, by fusing the NoLS to MafG,
      part of the nuclear transcription factor NF-E2 composed of both MafG and p45 NF
      E2, NF-E2 is redirected from the nucleoplasm to the nucleoli. Thus, we propose
      that the NoLS may be used as a tool to visualize and prove protein interactions
      in a cellular context.

PMID- 17179203
TI  - Expression and function of alpha-smooth muscle actin during embryonic-stem-cell
      derived cardiomyocyte differentiation.
AB  - Three alpha-muscle actin isoforms are sequentially expressed during in vivo
      cardiac development. alpha-Smooth muscle actin is first and transiently
      expressed, followed by alpha-skeletal and finally alpha-cardiac actin. The
      significance of these transitions in actin gene expression during myogenesis
      remains to be determined. To understand whether actin isoforms have specific
      functions during cardiac development and cardiomyocyte contractility, we have
      hampered alpha-smooth muscle and alpha-skeletal actin expression and organization
      during embryonic stem cell differentiation towards cardiomyocyte. We show that
      the sequence of actin isoform expression displays similar pattern in the in vitro
      model and in mouse heart embryogenesis. Treatment with an interfering fusion
      peptide containing the N-terminal sequence of alpha-smooth muscle actin during a
      time window preceding spontaneous beating, prevents proper cardiac
      sarcomyogenesis, whereas alpha-skeletal actin-fusion peptide has no effect.
      Knockdown of alpha-smooth muscle actin in embryonic stem cells using RNA
      interference also affects cardiac differentiation. The application of both fusion
      peptides on beating embryoid bodies impairs frequency. These results suggest
      specific functional activities for actin isoforms in cardiogenesis and
      cardiomyocyte contractility.

PMID- 17179204
TI  - Ena/VASP proteins mediate repulsion from ephrin ligands.
AB  - Ena/VASP proteins negatively regulate cell motility and contribute to repulsion
      from several guidance cues; however, there is currently no evidence for a role
      downstream of Eph receptors. Eph receptors mediate repulsion from ephrins at
      sites of intercellular contact during several developmental migrations. For
      example, the expression of ephrin-Bs in posterior halves of somites restricts
      neural crest cell migration to the anterior halves. Here we show that ephrin-B2
      destabilises neural crest cell lamellipodia when presented in a substrate-bound
      or soluble form. Our timelapse studies show that repulsive events are associated
      with the rearward collapse and subsequent loss of lamellipodia as membrane
      ruffles. We hypothesise that Ena/VASP proteins contribute to repulsion from
      ephrins by destabilising cellular protrusions and show that Ena/VASP-deficient
      fibroblasts exhibit reduced repulsion from both ephrin-A and ephrin-B stripes
      compared to wild-type controls. Moreover, when EphB4 and ephrin-B2 were expressed
      in neighbouring Swiss 3T3 fibroblasts, VASP and Mena co-accumulated with
      activated Eph receptors at protrusions formed by EphB4-expressing cells.
      Sequestration of Ena/VASP proteins away from the periphery of these cells
      inhibited Eph receptor internalisation, a process that facilitates repulsion. Our
      results suggest that Ena/VASP proteins regulate ephrin-induced Eph receptor
      signalling events, possibly by destabilising lamellipodial protrusions.

PMID- 17179205
TI  - Beta cells occur naturally in extrahepatic bile ducts of mice.
AB  - Insulin-secreting beta cells were thought to reside only in the pancreas. Here,
      we show that beta cells are also present in the extra-hepatic bile ducts of mice.
      They are characterised by insulin and C-peptide content, the presence of
      secretory granules that are immunoreactive for insulin, and the ducts exhibit
      glucose-stimulated insulin secretion. Genetic lineage labelling shows that these
      beta cells arise from the liver domain rather than the pancreas and, by
      histological study, they appear to be formed directly from the bile duct
      epithelium in late embryogenesis. Other endocrine cell types (producing
      somatostatin and pancreatic polypeptide) are also found in close association with
      the bile-duct-derived beta cells, but exocrine pancreatic tissue is not present.
      This discovery of beta cells outside the mammalian pancreas has implications for
      regenerative medicine, indicating that biliary epithelium might offer a new
      source of beta cells for the treatment of diabetes. The finding also has
      evolutionary significance, because it is known that certain basal vertebrates
      usually form all of their beta cells from the bile ducts. The mammalian bile-duct
      derived beta cells might therefore represent an extant trace of the evolutionary
      origin of the vertebrate beta cell.

PMID- 17179206
TI  - Synaptotagmin 3 deficiency in T cells impairs recycling of the chemokine receptor
      CXCR4 and thereby inhibits CXCL12 chemokine-induced migration.
AB  - Synaptotagmins regulate vesicle trafficking and fusion of vesicles with membranes
      - processes that have been implicated in cell migration. We therefore
      hypothesized that synaptotagmins play a role in T-cell migration. Amongst
      synaptotagmins 1-11, we found synaptotagmin 3 (SYT3) to be the only one that is
      expressed in T cells. CXCR4-triggered migration was inhibited by antisense
      synaptotagmin 3 mRNA and by the isolated C2B domain, known to impair
      oligomerization of all synaptotagmins, but not by a C2B mutant that binds Ca(2+)
      but does not block oligomerization. The C2B domain also blocked CXCR4-triggered
      actin polymerization and invasion. However, CXCR4-dependent adhesion in flow was
      not affected. Surprisingly, we found that little or no SYT3 is present near the
      plasma membrane but that it is mainly localized in multivesicular bodies, which
      also contained much of the CXCR4. Impaired SYT3 function blocked CXCR4 recycling
      and thus led to reduced surface levels of CXCR4. Migration was restored by
      overexpression of CXCR4. We conclude that STT3 is essential for CXCR4 recycling
      in T cells and thereby for the maintenance of high CXCR4 surface levels required
      for migration.

PMID- 17179207
TI  - A new activating role for CO in cardiac mitochondrial biogenesis.
AB  - To investigate a possible new physiological role of carbon monoxide (CO), an
      endogenous gas involved in cell signaling and cytotoxicity, we tested the
      hypothesis that the mitochondrial generation of reactive oxygen species by CO
      activates mitochondrial biogenesis in the heart. In mice, transient elevations of
      cellular CO by five- to 20-fold increased the copy number of cardiac
      mitochondrial DNA, the content of respiratory complex I-V and interfibrillar
      mitochondrial density within 24 hours. Mitochondrial biogenesis is activated by
      gene and protein expression of the nuclear respiratory factor 1 (NRF1) and NRF2,
      of peroxisome proliferator-activated receptor gamma co-activator-1alpha, and of
      mitochondrial transcription factor A (TFAM), which augmented the copy number of
      mitochondrial DNA (mtDNA). This is independent of nitric oxide synthase (NOS), as
      demonstrated by the identical responses in wild-type and endothelial NOS (eNOS)
      deficient mice, and by the inhibition of inducible NOS (iNOS). In the heart and
      in isolated cardiomyocytes, CO activation involved both guanylate cyclase and the
      pro-survival kinase Akt/PKB. Akt activation was facilitated by mitochondrial
      binding of CO and by production of hydrogen peroxide (H(2)O(2)). Interference
      with Akt activity by blocking PI 3-kinase and by mitochondrial targeting of
      catalase to scavenge H(2)O(2) prevented binding of NRF1 to the Tfam promoter,
      thereby connecting mitochondrial H(2)O(2) to the pathway leading to mtDNA
      replication. The findings disclose mitochondrial CO and H(2)O(2) as new
      activating factors in cardiac mitochondrial biogenesis.

PMID- 17179208
TI  - Molecular profile of mouse stromal mesenchymal stem cells.
AB  - We determined a transcriptional profile specific for clonal stromal mesenchymal
      stem cells from adult and fetal hematopoietic sites. To identify mesenchymal stem
      cell-like stromal cell lines, we evaluated the adipocytic, osteoblastic,
      chondrocytic, and vascular smooth muscle differentiation potential and also the
      hematopoietic supportive (stromal) capacity of six mouse stromal cell lines from
      adult bone marrow and day 14.5 fetal liver. We found that two lines were
      quadripotent and also supported hematopoiesis, BMC9 from bone marrow and AFT024
      from fetal liver. We then ascertained the set of genes differentially expressed
      in the intersection set of AFT024 and BMC9 compared with those expressed in the
      union set of two negative control lines, 2018 and BFC012 (both from fetal liver);
      346 genes were upregulated and 299 downregulated. Using Ingenuity software, we
      found two major gene networks with highly significant scores. One network
      contained downregulated genes that are known to be implicated in osteoblastic
      differentiation, proliferation, or transformation. The other network contained
      upregulated genes that belonged to two categories, cytoskeletal genes and genes
      implicated in the transcriptional machinery. The data extend the concept of
      stromal mesenchymal stem cells to clonal cell populations derived not only from
      bone marrow but also from fetal liver. The gene networks described should
      discriminate this cell type from other types of stem cells and help define the
      stem cell state.

PMID- 17179209
TI  - Congenic strains confirm aerobic running capacity quantitative trait loci on rat
      chromosome 16 and identify possible intermediate phenotypes.
AB  - We previously identified two inbred rat strains divergent for treadmill aerobic
      running capacity (ARC), the low-performing Copenhagen (COP) and the high
      performing DA rats, and used an F(2)(COPxDA) population to identify ARC
      quantitative trait loci (QTLs) on rat chromosome 16 (RNO16) and the proximal
      portion of rat chromosome 3 (RNO3). Two congenic rat strains were bred to further
      investigate these ARC QTLs by introgressing RNO16 and the proximal portion of
      RNO3 from DA rats into the genetic background of COP rats and were named
      COP.DA(chr 16) and COP.DA(chr 3), respectively. COP.DA(chr 16) rats had
      significantly greater ARC compared with COP rats (696.7 +/- 38.2 m vs. 571.9 +/-
      27.5 m, P = 0.03). COP.DA(chr 3) rats had increased, although not significant,
      ARC compared with COP rats (643.6 +/- 40.9 m vs. 571.9 +/- 27.5 m). COP.DA(chr
      16) rats had significantly greater subcutaneous abdominal fat, as well as
      decreased fasting triglyceride levels, compared with COP rats (P < 0.05),
      indicating that genes responsible for strain differences in fat metabolism are
      also located on RNO16. While this colocalization of QTLs may be coincidental, it
      is also possible that these differences in energy balance may be associated with
      the superior running performance of COP.DA(chr 16) consomic rats.

PMID- 17179210
TI  - Computationally designed libraries of fluorescent proteins evaluated by
      preservation and diversity of function.
AB  - To determine which of seven library design algorithms best introduces new protein
      function without destroying it altogether, seven combinatorial libraries of green
      fluorescent protein variants were designed and synthesized. Each was evaluated by
      distributions of emission intensity and color compiled from measurements made in
      vivo. Additional comparisons were made with a library constructed by error-prone
      PCR. Among the designed libraries, fluorescent function was preserved for the
      greatest fraction of samples in a library designed by using a structure-based
      computational method developed and described here. A trend was observed toward
      greater diversity of color in designed libraries that better preserved
      fluorescence. Contrary to trends observed among libraries constructed by error
      prone PCR, preservation of function was observed to increase with a library's
      average mutation level among the four libraries designed with structure-based
      computational methods.

PMID- 17179211
TI  - Mutations in the connection domain of HIV-1 reverse transcriptase increase 3'
      azido-3'-deoxythymidine resistance.
AB  - We previously proposed that a balance between nucleotide excision and template
      RNA degradation plays an important role in nucleoside reverse transcriptase
      inhibitor (NRTI) resistance. To explore the predictions of this concept, we
      analyzed the role of patient-derived C-terminal domains of HIV-1 reverse
      transcriptase (RT) in NRTI resistance. We found that when the polymerase domain
      contained previously described thymidine analog resistance mutations, mutations
      in the connection domain increased resistance to 3'-azido-3'-deoxythymidine (AZT)
      from 11-fold to as much as 536-fold over wild-type RT. Mutational analysis showed
      that amino acid substitutions E312Q, G335C/D, N348I, A360I/V, V365I, and A376S
      were associated strongly with the observed increase in AZT resistance; several of
      these mutations also decreased RT template switching, suggesting that they alter
      the predicted balance between nucleotide excision and template RNA degradation.
      These results indicate that mutations in the C-terminal domain of RT
      significantly enhance clinical NRTI resistance and should be considered in
      genotypic and phenotypic drug resistance studies.

PMID- 17179212
TI  - Site-specific collapse dynamics guide the formation of the cytochrome c' four
      helix bundle.
AB  - The evolution of tryptophan-to-heme (W/heme) distance distributions extracted
      from analysis of fluorescence energy transfer kinetics during the refolding of
      Rhodopseudomonas palustris cytochrome c' reveals dramatic differences between two
      variants [W32 (Q1A/F32W/W72F) and W72 (Q1A)]. Both W32/heme and W72/heme distance
      distributions measured at the earliest time point attainable with a continuous
      flow mixer (150 mus) confirm that the polypeptide ensemble is not uniformly
      collapsed and that native structure is not formed. Time-resolved fluorescence
      spectra indicate that W32 is sequestered from the aqueous solution during the
      first 700 mus of folding, whereas W72 remains exposed to solvent. The first
      moment of the W32/heme distance distribution evolves to its native value faster
      than that of W72, suggesting that the approach of W32 to the heme precedes that
      of W72.

PMID- 17179213
TI  - Reengineering CCA-adding enzymes to function as (U,G)- or dCdCdA-adding enzymes
      or poly(C,A) and poly(U,G) polymerases.
AB  - CCA-adding enzymes build and repair the 3'-terminal CCA sequence of tRNA. These
      unusual RNA polymerases use either a ribonucleoprotein template (class I) or pure
      protein template (class II) to form mock base pairs with the Watson-Crick edges
      of incoming CTP and ATP. Guided by the class II Bacillus stearothermophilus CCA
      adding enzyme structure, we introduced mutations designed to reverse the polarity
      of hydrogen bonds between the nucleobases and protein template. We were able to
      transform the CCA-adding enzyme into a (U,G)-adding enzyme that incorporates UTP
      and GTP instead of CTP and ATP; we transformed the related Aquifex aeolicus CC-
      and A-adding enzymes into UU- and G-adding enzymes and Escherichia coli poly(A)
      polymerase into a poly(G) polymerase; and we transformed the B.
      stearothermophilus CCA-adding enzyme into a poly(C,A) polymerase by mutations in
      helix J that appear, based on the apoenzyme structure, to sterically limit
      addition to CCA. We also transformed the B. stearothermophilus CCA-adding enzyme
      into a dCdCdA-adding enzyme by mutating an arginine that interacts with the
      incoming ribose 2' hydroxyl. Most importantly, we found that mutations in helix J
      can affect the specificity of the nucleotide binding site some 20 A away,
      suggesting that the specificity of both class I and II enzymes may be dictated by
      an intricate network of hydrogen bonds involving the protein, incoming
      nucleotide, and 3' end of the tRNA. Collaboration between RNA and protein in the
      form of a ribonucleoprotein template may help to explain the evolutionary
      diversity of the nucleotidyltransferase family.

PMID- 17179214
TI  - A PDZ domain recapitulates a unifying mechanism for protein folding.
AB  - A unifying view has been recently proposed according to which the classical
      diffusion-collision and nucleation-condensation models may represent two extreme
      manifestations of an underlying common mechanism for the folding of small
      globular proteins. We report here the characterization of the folding process of
      the PDZ domain, a protein that recapitulates the three canonical steps involved
      in this unifying mechanism, namely: (i) the early formation of a weak nucleus
      that determines the native-like topology of a large portion of the structure,
      (ii) a global collapse of the entire polypeptide chain, and (iii) the
      consolidation of the remaining partially structured regions to achieve the native
      state conformation. These steps, which are clearly detectable in the PDZ domain
      investigated here, may be difficult to distinguish experimentally in other
      proteins, which would thus appear to follow one of the two limiting mechanisms.
      The analysis of the (un)folding kinetics for other three-state proteins (when
      available) appears consistent with the predictions ensuing from this unifying
      mechanism, thus providing a powerful validation of its general nature.

PMID- 17179215
TI  - Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled
      receptors.
AB  - G protein-coupled receptors (GPCRs) play pivotal roles in cell proliferation,
      differentiation, and survival. Although many studies indicate that the
      stimulation of GPCRs leads to NF-kappaB activation, the molecular mechanism by
      which GPCRs induced NF-kappaB activation remains largely unknown. Bcl10 is an
      essential adaptor molecule connecting antigen receptor signaling cascades to NF
      kappaB activation in lymphocytes. However, the function of Bcl10 in nonlymphoid
      cells remains to be determined. In this study, we demonstrated that the
      deficiency of Bcl10 resulted in the defect in NF-kappaB activation induced by
      either expressing the constitutively active mutant of G protein or stimulation of
      cells with lysophosphatidic acid or endothelin-1, which activate their GPCR. In
      contrast, TNF-alpha-, LPS-, and integrin-induced NF-kappaB activation was not
      affected in Bcl10-deficient cells. Together, our results provide genetic evidence
      showing that Bcl10 is a key signaling component mediating NF-kappaB activation
      induced by GPCRs in nonlymphoid cells.

PMID- 17179216
TI  - A common mutational pattern in Cockayne syndrome patients from xeroderma
      pigmentosum group G: implications for a second XPG function.

PMID- 17179217
TI  - FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active
      regulatory elements from human chromatin.
AB  - DNA segments that actively regulate transcription in vivo are typically
      characterized by eviction of nucleosomes from chromatin and are experimentally
      identified by their hypersensitivity to nucleases. Here we demonstrate a simple
      procedure for the isolation of nucleosome-depleted DNA from human chromatin,
      termed FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements). To perform
      FAIRE, chromatin is crosslinked with formaldehyde in vivo, sheared by sonication,
      and phenol-chloroform extracted. The DNA recovered in the aqueous phase is
      fluorescently labeled and hybridized to a DNA microarray. FAIRE performed in
      human cells strongly enriches DNA coincident with the location of DNaseI
      hypersensitive sites, transcriptional start sites, and active promoters. Evidence
      for cell-type-specific patterns of FAIRE enrichment is also presented. FAIRE has
      utility as a positive selection for genomic regions associated with regulatory
      activity, including regions traditionally detected by nuclease hypersensitivity
      assays.

PMID- 17179218
TI  - Drug-eluting coronary stents: faith and hope, but no charity.

PMID- 17179220
TI  - Effect of hospital ownership status and payment structure on the adoption and use
      of drug-eluting stents for percutaneous coronary interventions.
AB  - BACKGROUND: The impact of the use of drug-eluting stents in percutaneous coronary
      intervention (PCI) on cardiac care is still uncertain. We examined the influence
      of systemic factors, such as hospital ownership status, organizational
      characteristics and payment structure, on the use of drug-eluting stents in PCI
      and the effect on cardiac surgery volume. METHODS: We conducted a cross-sectional
      analysis of drug-eluting stent use in 12 993 patients undergoing PCI with
      stenting (drug-eluting or bare-metal) and time-series regression analyses of the
      monthly number of cardiac surgery and PCI procedures performed using data
      collected from 1998 to 2004 at 13 public and private hospitals in the Emilia
      Romagna region of Italy. RESULTS: Public hospitals used drug-eluting stents more
      selectively than private hospitals, targeting the new device to patients at high
      risk of adverse events. The time-series regression analyses showed that the
      number of PCI procedures performed per year increased during this period, both in
      public (slope coefficient 36.4, 95% confidence interval [CI] 30.2 to 43.1) and
      private centres (slope coefficient 6.4, 95% CI 3.1 to 9.2 ). Concurrently, there
      was a reduction in the number of isolated coronary artery bypass graft (CABG)
      surgeries, although the degree of change was higher in public than in private
      hospitals (coefficient -16.1 v. -6.2 respectively ). The number of CABG
      procedures associated with valve surgery decreased in public hospitals
      (coefficient -5.0, 95% CI -6.1 to -3.8) but increased in private hospitals
      (coefficient 4.1, 95% CI 2.0 to 6.1). INTERPRETATION: Public and private
      hospitals behaved differently in adopting drug-eluting stents and in using PCI
      with drug-eluting stents as a substitute for surgical revascularization.

PMID- 17179219
TI  - The cost-effectiveness of drug-eluting stents: a systematic review.
AB  - BACKGROUND: Drug-eluting stents have been seen as an attractive alternative to
      bare-metal stents for percutaneous coronary interventions (PCIs) because of the
      decreased need for revascularization. However, comparative clinical trials have
      shown no difference in patient outcomes, and drug-eluting stents are considerably
      more expensive than their bare-metal counterparts. We conducted a systematic
      review of all published comparative cost-effectiveness analyses to identify the
      factors contributing to the heterogeneity of their conclusions. METHODS: We
      retrieved all articles published between Jan. 1, 2000, and July 31, 2006, in
      which the cost-effectiveness, from a third-party payer perspective, of drug
      eluting stents was compared with that of bare-metal stents for PCI in
      unrestricted patient populations. Electronic databases, Web sites from health
      technology assessment groups and references of identified articles were searched.
      Our outcome variable was whether the study's conclusions favoured widespread use
      of drug-eluting stents, as assessed by 4 independent reviewers. Study
      characteristics such as quality, funding source, country and year of publication
      were extracted. Two-by-2 tables and Fisher's exact test were used to study the
      association between covariates and the outcome variable. A classification and
      regression tree (CART) model was used for multivariate analysis. RESULTS: We
      identified 19 cost-effectiveness analyses. Ten were in favour of widespread use
      of drug-eluting stents, and 9 favoured more restrained use. Only 1 of 9 high
      quality studies supported widespread use, as compared with 9 of 10 lower quality
      studies (p < 0.001). All of the 7 sponsored studies argued in favour of
      widespread use, as compared with 3 of the 12 studies without sponsorship (p =
      0.003). Studies from the United States were more likely than those from other
      countries to endorse unlimited use (p = 0.032). A CART model with 2 covariates-
      study quality and sponsorship--provided the best fit (error rate 10.5%).
      INTERPRETATION: Conclusions drawn by cost-effectiveness analyses of drug-eluting
      stents for PCI are associated with the study's quality, funding source and
      country of origin. Vigilance regarding these study characteristics is required
      when interpreting findings from cost-effectiveness analyses.

PMID- 17179221
TI  - Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers
      coupled to the type I ribosome-inactivating protein saporin.
AB  - CD8+ cytotoxic T lymphocytes (CTLs) are important effector cells responsible for
      tissue destruction in several autoimmune and allograft-related diseases. To
      discover if pathogenic T cells could be selectively deleted, we investigated the
      ability of a toxin coupled to major histocompatibility complex (MHC) class I
      tetramers to kill antigen-specific CD8+ T cells. H2-D(b) tetramers were assembled
      using streptavidin conjugated to the ribosome-inactivating protein (RIP) saporin
      (SAP). These tetramers inhibited ribosome activity in vitro, retained the T-cell
      receptor (TCR)-binding specificity of their nontoxic counterparts, and were
      internalized by 100% of target cells, leading to cell death in 72 hours.
      Cytotoxicity was dependent on the tetramer dose and avidity for the T cell. A
      single injection of the SAP-coupled tetramer eliminated more than 75% of cognate,
      but not control, T cells. This work demonstrates the therapeutic potential of
      cytotoxic tetramers to selectively eradicate pathogenic clonotypes while leaving
      overall T-cell immunity intact.

PMID- 17179222
TI  - Influence of ERK activation on decreased chemotaxis of mature human cord blood
      monocyte-derived dendritic cells to CCL19 and CXCL12.
AB  - Dendritic cells (DCs) are important regulators in graft-versus-host disease
      (GVHD). To gain insight into cord blood (CB) DC immunology, we compared
      chemotactic responses of mature monocyte-derived DCs and maturation agent
      lipopolysaccharide (LPS)-induced signaling between CB and adult blood (AB).
      Mature CB DCs expressed reduced CCR7, but increased CXCR4. This was associated
      with reduced migratory efficiency toward both CCR7 ligand CCL19 and CXCR4 ligand
      CXCL12. LPS induced higher extracellular signal-regulated kinase (ERK)
      phosphorylation in CB than in AB DCs. Specific inhibition of ERK during CB DC
      maturation enhanced LPS-induced up-regulation of CCR7 and CXCR4 on CB DCs and
      their chemotaxis toward CCL19 and CXCL12, to a level similar to that of mature AB
      DCs. Overall, monocyte-derived CB DCs responded to LPS with stronger and
      sustained ERK activation, which negatively correlated with LPS-induced up
      regulation of CCR7 and CXCR4 on CB DCs and their migratory responses. These
      findings may have potential relevance to better understanding DC function in CB
      transplantation.

PMID- 17179224
TI  - Notch activity synergizes with B-cell-receptor and CD40 signaling to enhance B
      cell activation.
AB  - How diverse environmental cues are integrated to regulate B-cell activation and
      development remains poorly understood. Here we show that Notch activity
      synergizes with B-cell receptor (BCR) and/or CD40 signaling to enhance several
      aspects of B-cell activation and function. We find that costimulation of
      follicular B cells with the Notch ligand Delta-like-1 leads to significant
      increases in BCR- and CD40-mediated proliferation and enhances production of
      IgG1(+) cells in vitro and in vivo. We further find that coengagement of Notch
      and the BCR results in increased activation of the MAPK pathway, and MAPK and
      Notch inhibitors prevent B-cell activation events mediated by coengagement of
      Notch and the BCR. These data suggest that the BCR and CD40 signaling pathways
      collaborate with the Notch pathway to optimize B-cell activation.

PMID- 17179223
TI  - Members of the glutathione and ABC-transporter families are associated with
      clinical outcome in patients with diffuse large B-cell lymphoma.
AB  - Standard chemotherapy fails in 40% to 50% of patients with diffuse large B-cell
      lymphoma (DLBCL). Some of these failures can be salvaged with high-dose regimens,
      suggesting a role for drug resistance in this disease. We examined the expression
      of genes in the glutathione (GSH) and ATP-dependent transporter (ABC) families in
      2 independent tissue-based expression microarray datasets obtained prior to
      therapy from patients with DLBCL. Among genes in the GSH family, glutathione
      peroxidase 1 (GPX1) had the most significant adverse effect on disease-specific
      overall survival (dOS) in the primary dataset (n = 130) (HR: 1.68; 95% CI: 1.26
      2.22; P < .001). This effect remained statistically significant after controlling
      for biologic signature, LLMPP cell-of-origin signature, and IPI score, and was
      confirmed in the validation dataset (n = 39) (HR: 1.7; 95% CI: 1.05-2.8; P =
      .033). Recursive partitioning identified a group of patients with low-level
      expression of GPX1 and multidrug resistance 1 (MDR1; ABCB1) without early
      treatment failures and with superior dOS (P < .001). Overall, our findings
      suggest an important association of oxidative-stress defense and drug elimination
      with treatment failure in DLBCL and identify GPX1 and ABCB1 as potentially
      powerful biomarkers of early failure and disease-specific survival.

PMID- 17179225
TI  - Chemotherapy exposure increases leukemia cell stiffness.
AB  - Deformability of blood cells is known to influence vascular flow and contribute
      to vascular complications. Medications for hematologic diseases have the
      potential to modulate these complications if they alter blood cell deformability.
      Here we report the effect of chemotherapy on leukemia cell mechanical properties.
      Acute lymphoblastic and acute myeloid leukemia cells were incubated with standard
      induction chemotherapy, and individual cell stiffness was tracked with atomic
      force microscopy. When exposed to dexamethasone or daunorubicin, leukemia cell
      stiffness increased by nearly 2 orders of magnitude, which decreased their
      passage through microfluidic channels. This stiffness increase occurred before
      caspase activation and peaked after completion of cell death, and the rate of
      stiffness increase depended on chemotherapy type. Stiffening with cell death
      occurred for all cell types investigated and may be due to dynamic changes in the
      actin cytoskeleton. These observations suggest that chemotherapy itself may
      increase the risk of vascular complications in acute leukemia.

PMID- 17179226
TI  - Overexpression of nucleolin in chronic lymphocytic leukemia cells induces
      stabilization of bcl2 mRNA.
AB  - B-cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of
      clonal B cells that are resistant to apoptosis as a result of bcl2 oncogene
      overexpression. Studies were done to determine the mechanism for the up
      regulation of bcl-2 protein observed in CD19+ CLL cells compared with CD19+ B
      cells from healthy volunteers. The 11-fold higher level of bcl-2 protein in CLL
      cells was positively correlated with a 26-fold elevation in the cytosolic level
      of nucleolin, a bcl2 mRNA-stabilizing protein. Measurements of the bcl2
      heterogeneous nuclear/bcl2 mRNA (hnRNA)/mRNA ratios and the rates of bcl2 mRNA
      decay in cell extracts indicated that the 3-fold higher steady-state level of
      bcl2 mRNA in CLL cells was the result of increased bcl2 mRNA stability. Nucleolin
      was present throughout the nucleus and cytoplasm of CLL cells, whereas in normal
      B cells nucleolin was only detected in the nucleus. The addition of recombinant
      human nucleolin to extracts of normal B cells markedly slowed the rate of bcl2
      mRNA decay. SiRNA knockdown of nucleolin in MCF-7 cells resulted in decreased
      levels of bcl2mRNA and protein but no change in beta-actin. These results
      indicate that bcl-2 overexpression in CLL cells is related to stabilization of
      bcl2 mRNA by nucleolin.

PMID- 17179228
TI  - Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML.
AB  - The mTOR complex 2 (mTORC2) containing mTOR and rictor is thought to be rapamycin
      insensitive and was recently shown to regulate the prosurvival kinase AKT by
      phosphorylation on Ser473. We investigated the molecular effects of mTOR
      inhibition by the rapamycin derivatives (RDs) temsirolimus (CCI-779) and
      everolimus (RAD001) in acute myeloid leukemia (AML) cells. Unexpectedly, RDs not
      only inhibited the mTOR complex 1 (mTORC1) containing mTOR and raptor with
      decreased p70S6K, 4EPB1 phosphorylation, and GLUT1 mRNA, but also blocked AKT
      activation via inhibition of mTORC2 formation. This resulted in suppression of
      phosphorylation of the direct AKT substrate FKHR and decreased transcription of D
      cyclins in AML cells. Similar observations were made in samples from patients
      with hematologic malignancies who received RDs in clinical studies. Our study
      provides the first evidence that rapamycin derivatives inhibit AKT signaling in
      primary AML cells both in vitro and in vivo, and supports the therapeutic
      potential of mTOR inhibition strategies in leukemias.

PMID- 17179227
TI  - Selective targeting of the LIGHT-HVEM costimulatory system for the treatment of
      graft-versus-host disease.
AB  - Decoy lymphotoxin beta receptor (LTbetaR) has potent immune inhibitory activities
      and thus represents a promising biologic for the treatment of inflammation,
      autoimmune diseases, and graft-versus-host disease (GVHD). As this reagent
      interrupts multiple molecular interactions, including LTbeta-LTbetaR and LIGHT
      HVEM/LTbetaR, underlying molecular mechanisms have yet to be fully understood. In
      this study, we demonstrate that blockade of the LIGHT-HVEM pathway is sufficient
      to induce amelioration of GVHD in mouse models. Anti-host cytotoxic T lymphocyte
      (CTL) activity following in vivo transfer of allogeneic lymphocytes was
      completely abrogated when LIGHT- or HVEM-deficient (KO) T cells were used as
      donor cells. Accordingly, survival of the recipient mice following the transfer
      of allogeneic bone marrow cells plus LIGHT-KO or HVEM-KO T cells was
      significantly prolonged. In the absence of LIGHT-HVEM costimulation, alloreactive
      donor T cells undergo vigorous apoptosis while their proliferative potential
      remains intact. Furthermore, we prepared a neutralizing monoclonal antibody (mAb)
      specific to HVEM and showed that administration of anti-HVEM mAb profoundly
      ameliorated GVHD and led to complete hematopoietic chimerism with donor cells.
      Collectively, our results demonstrate an indispensable role of LIGHT-HVEM
      costimulation in the pathogenesis of GVHD and illustrate a novel target for
      selective immunotherapy in allogeneic bone marrow transplantation.

PMID- 17179230
TI  - A novel PAX5-ELN fusion protein identified in B-cell acute lymphoblastic leukemia
      acts as a dominant negative on wild-type PAX5.
AB  - We report a novel t(7;9)(q11;p13) translocation in 2 patients with B-cell acute
      lymphoblastic leukemia (B-ALL). By fluorescent in situ hybridization and 3' rapid
      amplification of cDNA ends, we showed that the paired box domain of PAX5 was
      fused with the elastin (ELN) gene. After cloning the full-length cDNA of the
      chimeric gene, confocal microscopy of transfected NIH3T3 cells and Burkitt
      lymphoma cells (DG75) demonstrated that PAX5-ELN was localized in the nucleus.
      Chromatin immunoprecipitation clearly indicated that PAX5-ELN retained the
      capability to bind CD19 and BLK promoter sequences. To analyze the functions of
      the chimeric protein, HeLa cells were cotransfected with a luc-CD19 construct,
      pcDNA3-PAX5, and with increasing amounts of pcDNA3-PAX5-ELN. Thus, in vitro, PAX5
      ELN was able to block CD19 transcription. Furthermore, real-time quantitative
      polymerase chain reaction (RQ-PCR) experiments showed that PAX5-ELN was able to
      affect the transcription of endogenous PAX5 target genes. Since PAX5 is essential
      for B-cell differentiation, this translocation may account for the blockage of
      leukemic cells at the pre-B-cell stage. The mechanism involved in this process
      appears to be, at least in part, through a dominant-negative effect of PAX5-ELN
      on the wild-type PAX5 in a setting ofPAX5 haploinsufficiency.

PMID- 17179229
TI  - Expression and release of soluble HLA-E is an immunoregulatory feature of
      endothelial cell activation.
AB  - Human leukocyte antigen (HLA)-E belongs, with HLA-G and HLA-F, to the non-classic
      major histocompatibility complex (MHC) class I (Ib) molecules, broadly defined by
      a limited polymorphism and a restricted pattern of cellular expression. In
      contrast to HLA-G, the expression and function of HLA-E and HLA-F in physiologic
      and pathologic processes remain poorly established. In the present study, we show
      that HLA-E protein expression in normal human nonlymphoid organs is mainly
      restricted to endothelial cells (ECs). HLA-E is also basally expressed by B and T
      lymphocytes, natural killer (NK) cells and by macrophages. We demonstrate that
      tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and
      interferon gamma (IFNgamma) up-regulate the cell-surface expression of HLA-E on
      ECs in vitro and induce the release of soluble HLA-E (sHLA-E). HLA-E up
      regulation protects IFN-gamma-activated ECs from NK-mediated cell lysis, while
      sHLA-E protects bystander cells. Finally, sHLA-E is not detected in normal sera,
      and increased serum levels correlate with disease activity in patients with
      antineutrophil cytoplasmic antibody-associated systemic vasculitis. Thus, HLA-E
      expression and release of sHLA-E are features of EC activation and emphasize
      immunoregulatory functions of the endothelium. The present identification of
      soluble HLA-E molecules may have important implications in understanding the
      pathogenesis of immune-mediated vascular diseases and for the diagnosis and
      monitoring of patients.

PMID- 17179231
TI  - Reduction of GVHD and enhanced antitumor effects after adoptive infusion of
      alloreactive Ly49-mismatched NK cells from MHC-matched donors.
AB  - We investigated if an infusion of alloreactive natural killer (NK) cells would
      reduce GVHD and mediate antitumor effects in mice undergoing MHC-matched
      allogeneic stem cell transplantation (SCT). Balb/c mice bearing RENCA tumors
      underwent an allogeneic SCT from MHC-matched B10.d2 donors and were given a
      single infusion of either Ly49 ligand-matched, ligand-mismatched, or no donor NK
      cells. Recipients of Ly49 ligand-mismatched NK cells had a reduced incidence of
      graft-versus-host disease (GVHD; 39% vs 100%; P < .01), and prolonged survival
      (median 84 days vs 39 days; P < .01) compared with SCT recipients not receiving
      NK cells. Recipients of Ly49 ligand-matched NK cells had the same incidence of
      GVHD and similar survival compared with controls not receiving NK cells.
      Pulmonary tumor burden was significantly (P < .01) lower in recipients that
      received Ly49-mismatched or Ly49-matched NK cells compared with recipients not
      receiving NK cells. These data provide in vivo evidence that a single infusion of
      alloreactive donor NK cells reduces GVHD and mediates antitumor effects following
      MHC-matched allogeneic transplantation.

PMID- 17179233
TI  - Nonmalignant T cells stimulate growth of T-cell lymphoma cells in the presence of
      bacterial toxins.
AB  - Bacterial toxins including staphylococcal enterotoxins (SEs) have been implicated
      in the pathogenesis of cutaneous T-cell lymphomas (CTCLs). Here, we investigate
      SE-mediated interactions between nonmalignant T cells and malignant T-cell lines
      established from skin and blood of CTCL patients. The malignant CTCL cells
      express MHC class II molecules that are high-affinity receptors for SE. Although
      treatment with SE has no direct effect on the growth of the malignant CTCL cells,
      the SE-treated CTCL cells induce vigorous proliferation of the SE-responsive
      nonmalignant T cells. In turn, the nonmalignant T cells enhance proliferation of
      the malignant cells in an SE- and MHC class II-dependent manner. Furthermore, SE
      and, in addition, alloantigen presentation by malignant CTCL cells to irradiated
      nonmalignant CD4(+) T-cell lines also enhance proliferation of the malignant
      cells. The growth-promoting effect depends on direct cell-cell contact and
      soluble factors such as interleukin-2. In conclusion, we demonstrate that SE
      triggers a bidirectional cross talk between nonmalignant T cells and malignant
      CTCL cells that promotes growth of the malignant cells. This represents a novel
      mechanism by which infections with SE-producing bacteria may contribute to
      pathogenesis of CTCL.

PMID- 17179234
TI  - NK4, an antagonist of hepatocyte growth factor (HGF), inhibits growth of multiple
      myeloma cells: molecular targeting of angiogenic growth factor.
AB  - Hepatocyte growth factor (HGF) promotes cell growth and motility and also
      increases neovascularization. Multiple myeloma (MM) cells produce HGF, and the
      plasma concentration of HGF is significantly elevated in patients with clinically
      active MM, suggesting that HGF might play a role in the pathogenesis of MM. NK4,
      an antagonist of HGF, is structurally homologous to angiostatin, and our previous
      report showed that NK4 inhibited the proliferation of vascular endothelial cells
      induced by HGF stimulation. The purposes of this study were to elucidate the
      contribution of HGF to the growth of MM cells as well as to investigate the
      possibility of the therapeutic use of NK4. In vitro study showed that NK4 protein
      stabilized the growth of MM cell lines and regulated the activation of c-MET,
      ERK1/2, STAT3, and AKT-1. Recombinant adenovirus containing NK4 cDNA (AdCMV.NK4)
      was injected intramuscularly into Icr/scid mice bearing tumors derived from HGF
      producing MM cells. AdCMV.NK4 significantly inhibited the growth of these tumors
      in vivo. Histologic examination revealed that AdCMV.NK4 induced apoptosis of MM
      cells, accompanied by a reduction in neovascularization in the tumors. Thus, NK4
      inhibited the growth of MM cells via antiangiogenic as well as direct antitumor
      mechanisms. The molecular targeting of HGF by NK4 could be applied as a novel
      therapeutic approach to MM.

PMID- 17179232
TI  - Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in
      adults with refractory and relapsed acute leukemias.
AB  - MS-275 is a benzamide derivative with potent histone deacetylase (HDAC)
      inhibitory and antitumor activity in preclinical models. We conducted a phase 1
      trial of orally administered MS-275 in 38 adults with advanced acute leukemias.
      Cohorts of patients were treated with MS-275 initially once weekly x 2, repeated
      every 4 weeks from 4 to 8 mg/m2, and after 13 patients were treated, once weekly
      x 4, repeated every 6 weeks from 8 to 10 mg/m2. The maximum-tolerated dose was 8
      mg/m2 weekly for 4 weeks every 6 weeks. Dose-limiting toxicities (DLTs) included
      infections and neurologic toxicity manifesting as unsteady gait and somnolence.
      Other frequent non-DLTs were fatigue, anorexia, nausea, vomiting,
      hypoalbuminemia, and hypocalcemia. Treatment with MS-275 induced increase in
      protein and histone H3/H4 acetylation, p21 expression, and caspase-3 activation
      in bone marrow mononuclear cells. No responses by classical criteria were seen.
      Our results show that MS-275 effectively inhibits HDAC in vivo in patients with
      advanced myeloid leukemias and should be further tested, preferably in patients
      with less-advanced disease.

PMID- 17179235
TI  - Perioperative beta-blockade: how best to translate evidence into practice.

PMID- 17179236
TI  - Thinking like a pancreas: perioperative glycemic control.

PMID- 17179237
TI  - Pro: Beta-blockers are indicated for patients at risk for cardiac complications
      undergoing noncardiac surgery.

PMID- 17179238
TI  - Con: Beta-blockers are indicated for all adults at increased risk undergoing
      noncardiac surgery.

PMID- 17179239
TI  - ACC/AHA 2006 guideline update on perioperative cardiovascular evaluation for
      noncardiac surgery: focused update on perioperative beta-blocker therapy--a
      report of the American College of Cardiology/American Heart Association Task
      Force on Practice Guidelines (Writing Committee to Update the 2002 Guidelines on
      Perioperative Cardiovascular Evaluation for Noncardiac Surgery).
AB  - The American College of Cardiology/American Heart Association (ACC/AHA) Task
      Force on Practice Guidelines makes every effort to avoid any actual, potential,
      or perceived conflict of interest that might arise as a result of an industry
      relationship or personal interest of the writing committee. Specifically, all
      members of the writing committee, as well as peer reviewers of the document, were
      asked to provide disclosure statements of all such relationships that might be
      perceived as real or potential conflicts of interest. These statements are
      reviewed by the parent task force, reported orally to all members of the writing
      committee at each meeting, and updated and reviewed by the writing committee as
      changes occur. Please see Appendix 1 for author relationships with industry and
      Appendix 2 for peer reviewer relationships with industry. These guidelines
      attempt to define practices that meet the needs of most patients in most
      circumstances. These guideline recommendations reflect a consensus of expert
      opinion after a thorough review of the available, current scientific evidence and
      are intended to improve patient care. If these guidelines are used as the basis
      for regulatory/payer decisions, the ultimate goal is quality of care and serving
      the patient's best interests. The ultimate judgment regarding care of a
      particular patient must be made by the healthcare provider and patient in light
      of all the circumstances presented by that patient.

PMID- 17179240
TI  - Perioperative beta-blockers for preventing surgery-related mortality and
      morbidity: a systematic review and meta-analysis.
AB  - BACKGROUND: Perioperative beta-blockers are suggested to reduce cardiovascular
      mortality, myocardial-ischemia/infarction, and supraventricular arrhythmias after
      surgery. We reviewed the evidence regarding the effectiveness of perioperative
      beta-blockers for improving patient outcomes after cardiac and noncardiac
      surgery. METHODS: Eleven large databases were searched from the time of their
      inception until October 2005. Various online-resources were consulted for the
      identification of unpublished trials and conference abstracts. We included
      randomized, controlled trials comparing perioperative beta-blockers with either
      placebo or the standard-of-care. Of the 3680 retrieved titles, 69 met inclusion
      criteria for analysis. Odds ratios (OR) assuming random effects were computed in
      the absence of significant clinical heterogeneity. RESULTS: Beta-blockers reduced
      the frequency of ventricular tachyarrhythmias [OR (cardiac surgery): 0.28, 95% CI
      0.13-0.57; OR (noncardiac surgery): 0.56, 95% CI 0.21-1.45], atrial
      fibrillation/flutter [OR (cardiac surgery): 0.37, 95% CI 0.28-0.48], other
      supraventricular arrhythmias [OR (cardiac surgery): 0.25, 95% CI 0.18-0.35; OR
      (noncardiac surgery): 0.43, 95% CI 0.14-1.37], and myocardial ischemia [OR
      (cardiac surgery): 0.49, 95% CI 0.17-1.4; OR (noncardiac surgery): 0.38, 95% CI
      0.21-0.69]. Length of hospitalization was not reduced [weighted mean difference
      (cardiac surgery): -0.35 days, 95% CI -0.77-0.07; weighted mean difference
      (noncardiac surgery): -5.59 days, 95% CI -12.22-1.04] and, in contrast to
      previous reports, beta-blockers did not reduce mortality [OR (cardiac surgery):
      0.55, 95% CI 0.17-1.83; OR (noncardiac surgery): 0.78, 95% CI 0.33-1.87], and
      they had no influence on the occurrence of perioperative myocardial infarction
      [OR (cardiac surgery): 0.89, 95% CI 0.53-1.5; OR (noncardiac surgery): 0.59; 0.25
      1.39]. CONCLUSIONS: Beta-blockers reduced perioperative arrhythmias and
      myocardial ischemia, but they had no effect on myocardial infarction, mortality,
      or length of hospitalization.

PMID- 17179241
TI  - Recent metformin ingestion does not increase in-hospital morbidity or mortality
      after cardiac surgery.
AB  - BACKGROUND: Perioperative treatment of type 2 diabetes with metformin, an oral
      hypoglycemic drug, is thought to increase the risk of life-threatening
      postoperative lactic acidosis. In contrast, metformin improves serum glucose
      control and has beneficial cardiovascular effects, which may decrease the risk of
      adverse outcomes. In this investigation we sought to determine the influence of
      metformin treatment on mortality and morbidity compared with treatment with other
      oral hypoglycemic drugs in diabetic patients undergoing cardiac surgery. METHODS:
      In this retrospective investigation, 1284 diabetic patients, with recent oral
      hypoglycemic ingestion (presumed to be 8-24 h preoperatively), underwent cardiac
      surgery from 1994-2004. Propensity scores were calculated from a logistic model
      which included baseline characteristics and perioperative variables. Four-hundred
      forty-three (85%) of the metformin-treated patients were matched on nearest
      propensity score using greedy matching techniques with 443 nonmetformin-treated
      patients. Postoperative outcomes were compared between matched metformin- and
      nonmetformin-treated patients. RESULTS: In-hospital mortality, cardiac, renal,
      and neurologic morbidities were similar between groups. Metformin-treated
      patients had less postoperative prolonged tracheal intubation [OR (95% CI), 0.3
      (0.1, 0.7), P = 0.003], infection [0.2 (0.1, 0.7), P = 0.007] and overall
      morbidities [0.4 (0.2, 0.8), P = 0.005]. CONCLUSIONS: These data suggest that
      recent metformin ingestion is not associated with increased risk of adverse
      outcome in cardiac surgical patients. Alternatively, metformin treatment may have
      beneficial effects.

PMID- 17179242
TI  - Monitoring brain oxygen saturation during coronary bypass surgery: a randomized,
      prospective study.
AB  - BACKGROUND: Cerebral deoxygenation is associated with various adverse systemic
      outcomes. We hypothesized, by using the brain as an index organ, that
      interventions to improve cerebral oxygenation would have systemic benefits in
      cardiac surgical patients. METHODS: Two-hundred coronary artery bypass patients
      were randomized to either intraoperative cerebral regional oxygen saturation
      (rSO2) monitoring with active display and treatment intervention protocol
      (intervention, n = 100), or underwent blinded rSO2 monitoring (control, n = 100).
      Predefined clinical outcomes were assessed by a blinded observer. RESULTS:
      Significantly more patients in the control group demonstrated prolonged cerebral
      desaturation (P = 0.014) and longer duration in the intensive care unit (P =
      0.029) versus intervention patients. There was no difference in overall incidence
      of adverse complications, but significantly more control patients had major organ
      morbidity or mortality (death, ventilation >48 h, stroke, myocardial infarction,
      return for re-exploration) versus intervention group patients (P = 0.048).
      Patients experiencing major organ morbidity or mortality had lower baseline and
      mean rSO2, more cerebral desaturations and longer lengths of stay in the
      intensive care unit and postoperative hospitalization, than patients without such
      complications. There was a significant (r(2) = 0.29) inverse correlation between
      intraoperative rSO2 and duration of postoperative hospitalization in patients
      requiring > or =10 days postoperative length of stay. CONCLUSION: Monitoring
      cerebral rSO2 in coronary artery bypass patients avoids profound cerebral
      desaturation and is associated with significantly fewer incidences of major organ
      dysfunction.

PMID- 17179243
TI  - Qualitative thrombelastographic detection of tissue factor in human plasma.
AB  - BACKGROUND: Tissue factor (TF) is the principal in vivo initiator of coagulation,
      with normal circulating TF concentrations reported to be approximately 23-158
      pg/mL. However, patients with atherosclerosis or cancer have been reported to
      have TF concentrations ranging between 800 and 9000 pg/mL. Of interest,
      thrombelastographic (TEG)-based measures of clot initiation and propagation have
      demonstrated hypercoagulability in such patients at risk for thromboembolic
      events. Thus, our goal in the present investigation was to establish a
      concentration-response relationship of the effect of TF on TEG variables, and
      determine specificity of TF-mediated events with a monoclonal TF antibody.
      METHODS: Thrombelastography was performed on normal human plasma exposed to 0,
      500, 1000, or 2000 pg/mL TF. Additional experiments with plasma exposed to 0 or
      750 pg/mL TF in the presence or absence of a monoclonal TF antibody (1:360
      dilution, 10 min incubation) were also performed. Clot initiation time (R) and
      the speed of clot propagation (MRTG, maximum rate of thrombus generation) were
      determined. RESULTS: The addition of TF to normal plasma resulted in a
      significant, concentration-dependent decrease in R and increase MRTG values. The
      addition of TF antibody to samples with TF significantly increased R and
      decreased MRTG values compared to samples with TF addition. CONCLUSIONS: In
      conclusion, changes in TEG variables in conjunction with use of a TF antibody can
      detect pathological concentrations of TF in human plasma in vitro. Further
      investigation is warranted to determine if TEG(R)-based monitoring could assist
      in the detection and prevention of TF-initiated thromboembolic events.

PMID- 17179244
TI  - The accuracy of electrocardiogram-controlled central line placement.
AB  - BACKGROUND: Electrocardiogram (ECG) guidance to confirm accurate positioning of
      central venous catheters (CVC), placed before surgery in the operating room, is
      rarely used in the United States. We designed this randomized, controlled trial
      to investigate whether the use of this technique impacts the accuracy of CVC
      placement. METHODS: Patients in group ECG (n = 147) had a CVC placed using right
      atrial ECG to guide catheter tip positioning. CVCs in group NO-ECG (n = 143) were
      positioned without this technique. RESULTS: Overall, guidewire-ECG control
      resulted in more correctly positioned CVCs (96% vs 76%, P < or = 0.001) without
      increasing placement time. Significantly more CVCs were placed in the middle of
      the superior vena cava in group ECG (P < or = 0.001), although placement into the
      right atrium or right ventricle and into other vessels occurred significantly
      more often in group NO-ECG (P < or = 0.001). Twenty patients in group NO-ECG
      required repositioning of their CVC after surgery, whereas this maneuver was
      necessary only in three patients in group ECG (P < or = 0.001). CONCLUSIONS: ECG
      guidance allows for more accurate CVC placement, and should be considered to
      increase patient safety and reduce costs associated with repositioning
      procedures.

PMID- 17179245
TI  - Successful cardiac resynchronization therapy after cardiac surgery.
AB  - Cardiac resynchronization therapy improves symptoms and survival in chronic heart
      failure patients, but has been poorly studied in the acute heart failure setting.
      We report the case of successful cardiac resynchronization therapy in the early
      postoperative period after cardiac surgery in a patient with left bundle branch
      block and proven ventricular dyssynchrony.

PMID- 17179246
TI  - Unexpected periaortic cavity during heart surgery.

PMID- 17179247
TI  - Remifentanil requirements during propofol administration to block the somatic
      response to skin incision in children and adults.
AB  - BACKGROUND: During sevoflurane administration, children require a remifentanil
      infusion rate twofold higher than adults to block responses to skin incision.
      Similar data concerning remifentanil requirements are unavailable during total IV
      anesthesia. METHODS: We prospectively determined the infusion rate (IR) of
      remifentanil necessary to block the somatic response to skin incision in 50%
      (IR50) of adults (n = 20, aged 20-60 yr) and children (n = 20, aged 3-11 yr)
      during propofol anesthesia. In each patient undergoing lower abdominal surgery, a
      remifentanil infusion was initiated, followed by target-controlled infusion of
      propofol set at a plasma concentration of 6 mug/mL. After tracheal intubation,
      propofol was reduced to 3 microg/mL until the end of the study. Remifentanil IR
      was determined according to Dixon's up-and-down method, with the first patient in
      each group receiving 0.2 microg x kg(-1) x min(-1) followed by the consecutive
      patient receiving 0.02 microg x kg(-1) x min(-1) modifications according to the
      response of the previous patient. The remifentanil IR was kept unchanged for at
      least 20 min before surgery. At the beginning of surgery, only the skin incision
      was performed, and the somatic response was observed. If there was any gross
      movement of extremity the response was considered positive. RESULTS: The IR50
      (CI(95%)) was 0.08 (0.06-0.12) microg x kg(-1) x min(-1) in adults and 0.15 (0.13
      0.17) microg x kg(-1) x min(-1) in children (P < 0.001). CONCLUSION: These
      results demonstrate that, similar to sevoflurane anesthesia, during total IV
      anesthesia with propofol, children require a remifentanil IR almost twofold
      higher than adults to block the somatic response to skin incision.

PMID- 17179248
TI  - Unrecognized anomalous origin of the left coronary artery from the pulmonary
      artery as a cause of ventricular fibrillation after patent ductus arteriosus
      ligation in an infant.
AB  - We present a case of an infant who developed ventricular fibrillation after
      patent ductus arteriosus (PDA) ligation. The infant had unrecognized anomalous
      origin of the left coronary artery from the pulmonary artery before PDA ligation.
      Acute reduction in systemic pulmonary artery pressures after PDA ligation
      resulted in an abrupt reduction in left main coronary artery blood flow. After
      prompt resuscitation, cardiac catheterization confirmed the diagnosis of
      anomalous origin of the left coronary artery from the pulmonary artery. The
      infant subsequently underwent coronary artery translocation and recovered
      uneventfully.

PMID- 17179249
TI  - Emergence delirium in children: many questions, few answers.
AB  - The introduction of a new generation of inhaled anesthetics into pediatric
      clinical practice has been associated with a greater incidence of ED, a short
      lived, but troublesome clinical phenomenon of uncertain etiology. A variety of
      anesthesia-, surgery-, patient-, and adjunct medication-related factors have been
      suggested to play a potential role in the development of such an event. Restless
      behavior upon emergence causes not only discomfort to the child, but also makes
      the caregivers and parents feel unhappy with the quality of recovery from
      anesthesia. Although the severity of agitation varies, it often requires
      additional nursing care, as well as treatment with analgesics or sedatives, which
      may delay discharge from hospital. To reduce the incidence of this adverse event,
      it is advisable to identify children at risk and take preventive measures, such
      as reducing preoperative anxiety, removing postoperative pain, and providing a
      quiet, stress-free environment for postanesthesia recovery. More clinical trials
      are needed to elucidate the cause as well as provide effective treatment.

PMID- 17179250
TI  - Transdermal scopolamine: an alternative to ondansetron and droperidol for the
      prevention of postoperative and postdischarge emetic symptoms.
AB  - BACKGROUND: Given the controversy regarding the use of droperidol and the high
      cost of the 5-HT3 antagonists, a cost-effective alternative for routine use as a
      prophylactic antiemetic would be desirable. We designed two parallel, randomized,
      double-blind sham and placebo-controlled studies to compare the early and late
      antiemetic efficacy and adverse event profile of transdermal scopolamine (TDS)
      1.5 mg, to ondansetron 4 mg IV, and droperidol 1.25 mg IV for antiemetic
      prophylaxis as part of a multimodal regimen in "at risk" surgical populations.
      METHODS: A total of 150 patients undergoing major laparoscopic (n = 80) or
      plastic (n = 70) surgery procedures received either an active TDS patch
      (containing scopolamine 1.5 mg) or a similar appearing sham patch 60 min before
      entering the operating room. All patients received a standardized general
      anesthetic technique. A second study medication was administered in a 2-mL
      numbered syringe containing either saline (for the two active TDS groups),
      droperidol, 1.25 mg, or ondansetron, 4 mg (for the sham patch groups), and was
      administered IV near the end of the procedure. The occurrence of postoperative
      nausea and vomiting/retching, need for rescue antiemetics, and the complete
      response rates (i.e., absence of protracted nausea or repeated episodes of emesis
      requiring antiemetic rescue medication) was reported. In addition, complaints of
      visual disturbances, dry mouth, drowsiness, and restlessness were noted up to 72
      h after surgery. RESULTS: There were no significant differences in any of the
      emetic outcomes or need for rescue antiemetics among the TDS, droperidol, and
      ondansetron groups in the first 72 h after surgery. The complete response rates
      varied from 41% to 51%, and did not significantly differ among the treatment
      groups. The overall incidence of dry mouth was significantly more frequent in the
      TDS groups than in the droperidol and ondansetron groups (21% vs 3%).
      CONCLUSIONS: Premedication with TDS was as effective as droperidol (1.25 mg) or
      ondansetron (4 mg) in preventing nausea and vomiting in the early and late
      postoperative periods. However, the use of a TDS patch is more likely to produce
      a dry mouth.

PMID- 17179252
TI  - A randomized prospective study comparing the Cobra Perilaryngeal Airway and
      Laryngeal Mask Airway-Classic during controlled ventilation for gynecological
      laparoscopy.
AB  - BACKGROUND: An increasing number of noninvasive, supraglottic airway devices are
      currently available. In this randomized single-blind study, we compared the Cobra
      Perilaryngeal Airway (CobraPLA) to the [Laryngeal Mask Airway (LMA)-Classic]
      during gynecological laparoscopy. METHODS: Forty patients received either an LMA
      Classic or a CobraPLA. Insertion, ventilation and removal characteristics were
      noted, as well as any throat morbidity. RESULTS: Devices were similar for
      insertion characteristics, adverse events, and throat morbidity. Before
      pneumoperitoneum, peak airway pressures were 20.3 +/- 4.9 cm H2O in the LMA
      Classic group versus 25.5 +/- 7.9 cm H2O in the CobraPLA group, P = 0.01. This
      difference was maintained during pneumoperitoneum; LMA-Classic (22.8 +/- 6.1 cm
      H2O) and CobraPLA (28.1 +/- 8.5 cm H2O), P = 0.04. Macroscopic blood occurred
      only on the CobraPLA, seen on 40% of the devices after removal, P = 0.001.
      CONCLUSION: During gynecological laparoscopy, the CobraPLA provides similar
      insertion characteristics, but higher airway sealing pressures than the LMA
      Classic. The usefulness of this finding requires further investigation.

PMID- 17179251
TI  - Premedication with gabapentin: the effect on tourniquet pain and quality of
      intravenous regional anesthesia.
AB  - BACKGROUND: Gabapentin, an oral non-opioid analgesic, has been used to decrease
      pain after a variety of surgical procedures. We hypothesized that premedication
      with gabapentin would minimize tourniquet-related pain in patients receiving IV
      regional anesthesia (IVRA). METHODS: Patients undergoing elective hand surgery
      with IVRA were randomly assigned to one of two study groups using a double-blind
      study design. The control group (n = 20) received placebo capsules 1 h before the
      surgery, and the gabapentin group (n = 20) received gabapentin 1.2 g p.o. before
      the operation. IVRA was achieved in all patients with lidocaine, 3 mg/kg, diluted
      with saline to a total volume of 40 mL. Fentanyl, 0.5 microg/kg IV, was
      administered as a rescue analgesic during surgery. Sensory and motor block onset
      and recovery times, tourniquet pain, and quality of anesthesia were assessed at
      specific time intervals during the perioperative period. Visual analog scale pain
      scores (0-10) were recorded during the 24 h follow-up period, and patients
      received diclofenac, 75 mg IM, if their pain score was >4. RESULTS: The onset of
      the sensory and motor block did not differ between the two study groups. However,
      tourniquet pain scores at 30, 40, 50, and 60 min after cuff inflation were lower
      in the gabapentin group (P < 0.05). The time to intraoperative analgesic rescue
      was prolonged in the gabapentin group (35 +/- 10 min vs 21 +/- 13 min, P < 0.05),
      and less supplemental fentanyl was required (35 +/- 47 microg vs 83 +/- 73
      microg, P < 0.05). The quality of anesthesia, as independently assessed by the
      anesthesiologist and the surgeon, was significantly better in the gabapentin
      (versus control) group. In the gabapentin group, the time to requesting a rescue
      analgesic after surgery was prolonged (135 +/- 25 min vs 85 +/- 19 min, P <
      0.05), and postoperative pain scores at 60 min (3.8 +/- 0.9 vs 2.2 +/- 0.5) and
      120 min (3.2 +/- 1.4 vs 1.8 +/- 0.8), as well as diclofenac consumption (30 +/-
      38 mg vs 60 +/- 63 mg), were reduced after surgery. CONCLUSIONS: Premedication
      with oral gabapentin (1.2 g) decreased tourniquet-related pain and improved the
      quality of anesthesia during hand surgery under IVRA. Gabapentin also reduced
      pain scores in the early postoperative period.

PMID- 17179253
TI  - Xenon blocks the induction of synaptic long-term potentiation in pain pathways in
      the rat spinal cord in vivo.
AB  - BACKGROUND: Xenon's (Xe) mechanisms for producing anesthesia and analgesia are
      not fully understood. We tested the effect of Xe equilibrated in a lipid
      formulation or normal saline on spinal C-fiber-evoked potentials and on the
      induction of synaptic long-term potentiation (LTP). METHODS: C-fiber-evoked field
      potentials were recorded in the superficial lumbar spinal cord in response to
      supramaximal electrical stimulation of the sciatic nerve. Anesthesia was
      maintained with isoflurane in one-third O2 and two-thirds N2O. Xe equilibrated at
      a concentration of 600 microL/mL of Lipofundin MCT(R) 20%, (n = 5) or solvent
      alone (n = 3), and Xe equilibrated at a concentration of 100 microL/mL of normal
      saline (n = 7) or saline alone (n = 7) was given IV under apnea. High-frequency
      stimulation of the sciatic nerve was applied 60 min after the injection of Xe
      containing formulations or solvents [to induce LTP]. RESULTS: High-frequency
      stimulation potentiated C-fiber-evoked potentials to 156% +/- 14% (mean +/- sem)
      of control. Low-dose Xe in saline 0.9% blocked the induction of LTP. High-dose Xe
      equilibrated in MC(R) 20% showed no additional effect when compared with the
      solvent, which blocked the induction of LTP. CONCLUSION: Low-dose Xe in saline
      0.9% revealed no antinociceptive, but preventive, action in spinal pain pathways.

PMID- 17179254
TI  - Propofol increases pulmonary vascular resistance during alpha-adrenoreceptor
      activation in normal and monocrotaline-induced pulmonary hypertensive rats.
AB  - BACKGROUND: Using isolated perfused lungs of normal or monocrotaline (MCT: 50
      mg/kg)-induced pulmonary hypertensive rats, we tested the hypothesis that the
      pulmonary vascular effects of propofol depend on activation of the alpha
      adrenoreceptor. METHODS: Changes in pulmonary perfusion pressure induced by
      propofol (10(-5) to 10(-4) M) were measured with or without phenylephrine (10(-6)
      M) pretreatment. Before phenylephrine administration, we assessed the effects of
      inhibitors of nitric oxide synthase (N(omega)-nitro-l-arginine methylester: 10(
      4) M), cyclooxygenase (indomethacin: 10(-5) M), and protein kinase C inhibitor,
      bisindolylmaleimide I (10(-6) M) or calphostin C (10(-6) M). RESULTS: Changes in
      pulmonary perfusion pressure by phenylephrine after pretreatment of nitric oxide
      synthase inhibitor and indomethacin in normal rats were significant (5 +/- 3 and
      7 +/- 2 mm Hg), whereas that after pretreatment of bisindolylmaleimide I were
      small in MCT-rats (2 +/- 1 mm Hg). Propofol caused pulmonary vasoconstriction
      after phenylephrine pretreatment both in normal and MCT-treated rats. In normal
      rats, the propofol-induced increase in pulmonary perfusion pressure after
      indomethacin pretreatment was slightly smaller than that in the non-pretreated
      lungs (P < 0.05). In MCT-treated rats, the propofol-induced increases in
      pulmonary perfusion pressure after both protein kinase C inhibitors were smaller
      than that in the non-pretreated lungs (P < 0.05). CONCLUSIONS: Propofol may
      increase pulmonary vascular resistance during alpha-adrenoreceptor activation.

PMID- 17179255
TI  - The effects of lidocaine and bupivacaine on protein expression of cleaved caspase
      3 and tyrosine phosphorylation in the rat hippocampal slice.
AB  - Severe neurologic sequelae have been reported with the use of lidocaine after
      spinal anesthesia. This is considered a consequence of the high concentrations
      reached in the cerebrospinal fluid. We have previously shown that lidocaine
      increases the phosphorylation of focal adhesion kinase (FAK, a nonreceptor
      tyrosine kinase playing a role in neuronal plasticity and cell death). Here, we
      compared the effects of lidocaine and bupivacaine on FAK phosphorylation and
      cleaved caspase 3 expression in rat hippocampal slices. Slices were treated with
      increasing concentrations of lidocaine (4.3 nM to 4.3 mM) or bupivacaine (3.4 nM
      to 3.4 mM) in the presence or absence of the specific inhibitor of the FAK
      tyrosine kinase PP2 (10 microM). Caspase 3 expression and FAK phosphorylation
      were examined by immunoblotting. Lidocaine induced a concentration-related
      increase in FAK phosphorylation while the bupivacaine effect was biphasic. The
      maximal effect observed with millimolar lidocaine concentrations was
      significantly more than with clinically equipotent bupivacaine concentrations
      (4.3 x 10(-3) M lidocaine: 168% +/- 20%, mean value +/- sd; 10(-3) M bupivacaine:
      145% +/- 19% P < 0.001). The expression of cleaved caspase 3 was increased by
      lidocaine, but not bupivacaine, at millimolar concentrations and was blocked by
      PP2. Our results indicate that millimolar concentrations of lidocaine, but not
      bupivacaine, increase cleaved caspase 3 expression. The role of FAK
      phosphorylation in this effect remains to be clarified.

PMID- 17179256
TI  - The hemodynamic effects of landiolol, an ultra-short-acting beta1-selective
      blocker, on endotracheal intubation in patients with and without hypertension.
AB  - BACKGROUND: The ultra-short-acting beta1-selective blocker, landiolol, is widely
      used in Japan. We investigated the effects of landiolol on intubation-induced
      adrenergic response in 88 patients. METHODS: General anesthesia was induced and
      maintained with target-controlled infusion of propofol at an effect-site
      concentration of 5 microg/mL. Muscle relaxation was obtained with 0.1 mg/kg
      vecuronium, and endotracheal intubation was performed 4 min after vecuronium
      injection. We first investigated the optimal time point for landiolol to be
      administered before intubation in 43 normotensive patients. Then we examined
      whether landiolol was as effective as fentanyl to prevent tachycardia after
      intubation in 45 hypertensive patients. RESULTS: Landiolol at 0.1 mg/kg was most
      effective against intubation-induced tachycardia when infused 4 min before
      intubation in normotensive patients. However, 0.2 mg/kg landiolol was necessary
      to prevent tachycardia after intubation in hypertensive patients. Landiolol had
      no significant effects on arterial blood pressure or bispectral index at any dose
      throughout the study period. In contrast, 2 mug/kg fentanyl frequently caused
      hypotension just before and 5 min after intubation. CONCLUSION: Low doses of
      landiolol can effectively prevent tachycardia after intubation without
      significant effects on arterial blood pressure.

PMID- 17179257
TI  - AnaConDa reflection filter: bench and patient evaluation of safety and volatile
      anesthetic conservation.
AB  - BACKGROUND: The AnaConDa filter permits administration of volatile anesthetic
      without the use of an anesthesia machine. It is intended for use in the intensive
      care unit. METHODS: We studied the AnaConDa reflection filter on the bench and in
      anesthetized patients. The bench analysis used a test lung, a gas analyzer, an
      intensive care ventilator, the AnaConDa filter, and a syringe pump. We studied a
      range of tidal volume, respiratory rate, and positive end-expiratory pressure
      values. We simulated errors during syringe refilling and patient transportation.
      In 15 anesthetized patients, we used the AnaConDa with constant ventilation
      variables, a constant sevoflurane infusion rate (4-5 mL/h), and two consecutive
      fresh gas flow levels. RESULTS: In the bench study, the expired volatile
      anesthetic fraction decreased linearly with respiratory frequency at constant
      minute ventilation, and decreased markedly in a hyperbolical manner when tidal
      volume increased at a constant respiratory rate. Changing the positive end
      expiratory pressure level and inspiration/expiration ratio did not modify the
      AnaConDa's performance. Several safety failures were observed: refilling caused a
      transient change in AnaConDa output because of a pumping effect, and a standard
      Luer lock made it possible to connect the halogenate syringe on an IV infusion
      line. In anesthetized patients, reducing fresh gas flow from 8 to 1 L/min led to
      a median 40% increase in the expired volatile anesthetic fraction. CONCLUSIONS:
      This study shows that the device is generally reliable, but that there are
      several conditions under which it might deliver more anesthetic than intended.

PMID- 17179258
TI  - Construction of the electroencephalogram player: a device to present
      electroencephalogram data to electroencephalogram-based anesthesia monitors.
AB  - BACKGROUND: Recently, an increasing number of electroencephalogram (EEG)-based
      monitors of the hypnotic component of anesthesia has become available. Most of
      these monitors calculate a numerical index reflecting the hypnotic component of
      anesthesia. Most of the underlying algorithms are proprietary. Therefore, a
      quality check or comparison of different indices is very complex. METHODS:
      Because there is limited information about the algorithms used for index
      calculation of the different monitors, a reliable comparison or test of the
      monitors is possible only if the same set of EEG data are presented to each
      monitor. RESULTS: Parallel EEG monitoring during surgery is limited to two or
      three monitors because the space for electrode placement on the head is limited.
      This problem can be solved by using the EEG player to play back recorded EEG data
      to different monitors. CONCLUSIONS: The output of the player corresponds to the
      original EEG signal. A comparison of different indices based on identical EEGs is
      therefore possible. The index reproducibility can also be checked, if the same
      signal is presented to different monitors.

PMID- 17179259
TI  - Six sigma methodology can be used to improve adherence for antibiotic prophylaxis
      in patients undergoing noncardiac surgery.
AB  - BACKGROUND: Six Sigma methodology is a data management process that can be used
      to achieve a goal of near perfection in process performance. An audit of 615
      surgeries over 2 mo revealed only 38% of noncardiac patients admitted on the day
      of surgery at our institution received perioperative antimicrobial prophylaxis
      within the target interval of < or =60 min before incision. METHODS: Six Sigma
      methodology was used to improve our process of timing of antimicrobial
      prophylaxis administration. A multidisciplinary team was assembled which
      identified seven process inputs by which patients receive antimicrobial
      prophylaxis. Interventions for improvement included reinforcement of use of
      preoperative antibiotic order forms, eliminating administration of antibiotics in
      the preoperative admission area, and sending appropriate antibiotics and IV
      tubing with the patient to the operating room. We concurrently developed a
      control plan to sustain this improvement using a recently deployed electronic
      anesthesia record keeping system using real-time measurement and reporting
      capabilities of antimicrobial prophylaxis administration. After defining the new
      process and undertaking a system-wide educational effort, implementation was
      begun with data collection and analysis occurring over the next 7 mo. RESULTS:
      For the 8-mo postintervention interval, there was a significant improvement with
      86% of 1716 surgical patients receiving their antibiotic prophylaxis within the
      specified time frame (P < 0.01). The time interval for antibiotic administration
      before surgical incision also decreased from a preintervention mean of 88 (CI 56
      119 min) to 38 min (CI 25-51 min) (P < 0.01). CONCLUSION: We conclude that Six
      Sigma methods were used to successfully improve our process for timing of
      perioperative antibiotic prophylaxis before surgical incision. An electronic
      anesthesia record keeping system is a useful tool to monitor this process
      improvement.

PMID- 17179260
TI  - An update on pediatric anesthesia liability: a closed claims analysis.
AB  - BACKGROUND: Respiratory complications were associated with half of pediatric
      malpractice claims from the 1970s to 1980s in the ASA Closed Claims Database.
      Advances in pediatric anesthesia practice have occurred in the 1980s and 1990s
      and may be reflected in liability trends. METHODS: We reviewed 532 pediatric (age
      < or =16 yr) malpractice claims from our database over three decades (1973-2000),
      using logistic regression analysis to evaluate trends over time. Claims from 1990
      to 2000 (1990s) were reviewed in detail to determine damaging events and
      injuries. Multiple logistic regression analysis evaluated factors associated with
      claims for death/brain damage (BD) compared with claims for less severe injuries.
      RESULTS: From 1973 to 2000, there was a decrease in the proportion of claims for
      death/BD (P = 0.002) and respiratory events (P < 0.001), particularly for
      inadequate ventilation/oxygenation (P < 0.001). However, claims for death (41%)
      and BD (21%) remained the dominant injuries in pediatric anesthesia claims in the
      1990s. Half of the claims in 1990-2000 involved patients 3 yr or younger and one
      fifth were ASA 3-5. Cardiovascular (26%) and respiratory (23%) events were the
      most common damaging events. Factors associated with claims for death/BD in the
      1990s when compared with claims for less severe injuries were cardiovascular
      events (odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.5-17.8),
      respiratory events (OR = 3.7, 95% CI = 1.5-9.4), and ASA status 3-5 (OR = 3.1,
      95% CI = 1.3-7.8). CONCLUSIONS: Death/BD remained the dominant injuries in
      pediatric anesthesia malpractice claims in the 1990s. Cardiovascular events
      joined respiratory events as the major sources of liability.

PMID- 17179261
TI  - A prospective study on anesthesia machine fault identification.
AB  - BACKGROUND: Although few studies have been performed recently, several have
      suggested that some practitioners are not well able to detect preset anesthesia
      machine faults. METHODS: We performed a prospective study to determine whether
      there is a correlation between duration of anesthesia practice and the ability to
      detect anesthesia machine faults. Our hypothesis was that more anesthesia
      practice would increase the ability to detect anesthesia machine faults. This
      study was performed during a nationally attended anesthesia meeting held at a
      large academic medical center, where 87 anesthesia providers were observed
      performing anesthesia machine checkouts. The participants were asked to
      individually check out an anesthesia machine with an unspecified number of preset
      faults. The primary outcome measures were the written listing of faults detected
      during an anesthesia machine checkout. RESULTS: Of the five faults preset into
      the test machine, participants with 0-2 yr experience detected a mean of 3.7
      faults, participants with 2-7 yr experience detected a mean of 3.6 faults, and
      participants with more than 7 yr experience detected a mean of 2.3 faults (P <
      0.001). CONCLUSIONS: Our prospective study demonstrated that anesthesia machine
      checkout continues to be a problem.

PMID- 17179262
TI  - Intrathoracic pressure regulation improves 24-hour survival in a porcine model of
      hypovolemic shock.
AB  - BACKGROUND: The intrathoracic pressure regulator (ITPR) plus positive pressure
      ventilation (PPV) has been shown to improve coronary and cerebral perfusion
      pressures during hypovolemia by improving mean arterial blood pressure and by
      decreasing right atrial and intracranial pressures. We hypothesized that
      application of intermittent negative intrathoracic pressure in a pig model of
      severe hypovolemic hypotension would increase 24-h neurological intact survival
      rates. METHODS: Eighteen isoflurane-anesthetized pigs were bled 55% of their
      estimated blood volume and were then prospectively randomized to either ITPR
      treatment with -8 mm Hg endotracheal pressure plus PPV or only PPV alone for 90
      min. All survivors were reinfused with their own blood. Arterial blood gases, end
      tidal CO2, and aortic pressures were monitored for the 90 min and neurological
      evaluation was performed at 12 and 24 h after reinfusion. RESULTS: ITPR plus PPV
      treatment for 90 min prevented the progression of metabolic acidosis and
      significantly improved mean arterial blood pressure (mean over 90 min, 55 +/- 3
      vs 35 +/- 2.4 mm Hg, P < 0.001) when compared with controls. Twenty-four hour
      survival significantly improved with use of the ITPR when compared with untreated
      controls: 9/9 (100%) vs 1/9 (11%), P < 0.01. CONCLUSIONS: Use of the ITPR plus
      PPV for 90 min significantly increased arterial blood pressure and 24 h
      neurologically intact survival rates compared with controls treated with PPV
      alone.

PMID- 17179263
TI  - Conversion locked-in syndrome after implantation of a spinal cord stimulator.
AB  - BACKGROUND: The locked-in syndrome is defined as quadriplegia and anarthria (loss
      of articulate speech) with the preservation of consciousness. It is typically
      caused by a lesion to the ventral pons. Conversion disorder is the deficit of
      voluntary motor or sensory function requiring an extensive work-up to exclude any
      organic cause. METHODS AND RESULTS: After surgery for an implantation of a spinal
      cord stimulator, a 42-year-old woman presented with quadriplegia and lower facial
      diplegia, but was able to open and blink her eyes. We found no organic causes to
      explain her condition after appropriate radiological studies looking for
      intracranial or intraspinal causes, and reversal drugs were administered with no
      immediate effect. Over the course of several hours, the patient gradually
      recovered and was discharged the following day. A psychology consultation was
      obtained during her stay and she was found to meet the criteria for a conversion
      disorder to explain her condition. CONCLUSIONS: Before considering a
      psychological cause, all organic factors should be excluded with proper tests and
      consultations, as conversion disorder is a diagnosis of exclusion. We report a
      patient who, after implantation of a spinal cord stimulator, manifested locked-in
      syndrome resulting from a conversion disorder.

PMID- 17179264
TI  - Postural orthostatic tachycardia syndrome: anesthetic implications in the
      obstetric patient.
AB  - We report the anesthetic management of a parturient with postural orthostatic
      tachycardia syndrome. This syndrome is associated with hemodynamic instability,
      which can be worsened by the physiology of labor and delivery. We discuss
      anesthetic concerns with this disease in the parturient and suggest approaches
      for management of this disease.

PMID- 17179265
TI  - Intravenous lidocaine after tracheal intubation mitigates bronchoconstriction in
      patients with asthma.
AB  - BACKGROUND: Although prophylactic IV administration of lidocaine attenuates the
      response to a variety of inhalation challenges, its effect on airway resistance
      after endotracheal intubation in patients with asthma is unclear. We tested the
      hypothesis that IV lidocaine attenuates intubation-evoked bronchoconstriction in
      patients with asthma. METHODS: Thirty patients with asthma (age 49.1 +/- 15.6 yr
      [mean +/- sd]) undergoing intubation after standardized anesthetic induction
      (etomidate 0.3 mg/kg, fentanyl 5 microg/kg, rocuronium 0.6 mg/kg, 50% nitrous
      oxide) were studied. Airway resistance was measured immediately after intubation
      and 5, 10, and 15 min later. Five minutes after intubation, either lidocaine (2
      mg/kg IV for 5 min, followed by 3 mg x kg(-1) x h(-1) for 10 min) or saline was
      administered. RESULTS: Airway resistance immediately after intubation averaged 23
      +/- 12 cm H2O x s x L(-1). Airway resistance further increased (+38%) after
      administration of saline, but decreased (-26%, P < 0.004) to less than the
      initial values after lidocaine. CONCLUSIONS: IV lidocaine given after
      endotracheal intubation mitigates bronchoconstriction in patients with asthma.

PMID- 17179266
TI  - The hypnotic, electroencephalographic, and antinociceptive properties of
      nonpeptide ORL1 receptor agonists after intravenous injection in rodents.
AB  - BACKGROUND: Agonists at the opioid receptor-like receptor 1 (ORL1) induce motor
      impairment, sedation, and loss of righting reflex (LRR) in rodents. This receptor
      may provide a novel target in the field of anesthesia. METHODS: We examined the
      hypnotic, electroencephalographic (EEG), and antinociceptive effects of two IV
      administered nonpeptide ORL1 agonists, (Ro 65-6570 and Org 26383), using LRR in
      mice and rats, percent EEG burst suppression in rats, and formalin paw test in
      mice. RESULTS: In mice, Ro 65-6570 and Org 26383 produced LRR (hypnotic dose 0.6
      and 3.7 micromol/kg for Ro 65-6570 and Org 26383, respectively). Naloxone had no
      significant effect on sleep times produced by both compounds. In rats, Ro 65-6570
      (0.6-2.4 micromol/kg) and Org 26383 (4-8 micromol/kg) produced LRR and burst
      suppression activity in the EEG. Both sleep times and burst suppression activity
      were significantly reduced with a selective ORL1 antagonist. In mice, dose
      dependent inhibition of formalin-induced nociceptive behaviors occurred (Phase 1
      ED50 0.4 and 1.8 micromol/kg and Phase 2 ED50 0.4 and 4.2 micromol/kg for Ro 65
      6570 and Org 26383, respectively). CONCLUSIONS: These results show that Ro 65
      6570 and Org 26383 (probably via the ORL1 receptor) behave as IV hypnotics and
      analgesics in mice and rats, and that the hypnotic and antinociceptive doses are
      similar.

PMID- 17179267
TI  - Levetiracetam reduces anesthetic-induced hyperalgesia in rats.
AB  - BACKGROUND: As part of an increase in excitability, small doses of pentobarbital,
      propofol, and midazolam induce an increased sensitivity to pain. Specific therapy
      to prevent or reduce this excitability may offer advantages over current clinical
      management with analgesics and sedatives. The pharmacological profile of the
      novel antiepileptic drug, levetiracetam, suggests that it may reduce the
      intensity of the excitatory stages of anesthesia. METHODS: We examined the
      influence of levetiracetam on the reduction of the nociceptive reflex threshold
      in rats by sedative doses of pentobarbital, propofol, and midazolam. Measurements
      of nociceptive reflex threshold to pressure and heat were made and then repeated
      after intraperitoneal injection of saline or one of three doses of levetiracetam
      (100, 200, 500 mg/kg). Pentobarbital (30 mg/kg), propofol (30 mg/kg), or
      midazolam (1.9 mg/kg) were then administered. The reflex threshold was measured
      every 10 min, starting at 5 min after the sedative injection, until 65 min had
      elapsed. RESULTS: Levetiracetam did not alter nociceptive reflex threshold in
      nonsedated animals (P = 0.11) or influence the degree or duration of sedation.
      The three anesthetic/sedative drugs reduced the nociceptive reflex threshold by
      20%-30% of control values. Levetiracetam reduced the hyperreflexia associated
      with pentobarbital and midazolam (P < 0.05), but not propofol. CONCLUSIONS: These
      findings support further investigation into the role of levetiracetam in the
      prevention of anesthetic-induced excitability.

PMID- 17179268
TI  - The effects of lipid infusion on myocardial function and bioenergetics in l
      bupivacaine toxicity in the isolated rat heart.
AB  - BACKGROUND: It is unclear whether improved metabolism or a "lipid sink" effect of
      lipid infusion is responsible for the positive effects in local anesthetic
      induced myocardial depression. METHODS: We used an isolated rat heart, constant
      pressure perfused, nonrecirculating Langendorff preparation and exposed hearts to
      5 mug/mL l-bupivacaine and 9 microL/mL lipid emulsion. Hearts were freeze-clamped
      and energy was charge measured by HPLC. In a second experiment the effects of
      pacing hearts was evaluated. The effects of lipid addition on local anesthetic
      concentrations in Krebs-Henseleit buffer and human plasma were examined by using
      a mass spectrometer. RESULTS: With spontaneously beating hearts l-bupivacaine led
      to a significant decrease in heart rate (to 74% +/- 7% of baseline), +dP/dt (69%
      +/- 7%), systolic pressure (78% +/- 6%), coronary flow (61% +/- 8%), and to an
      increase in PR (177% +/- 52%) and QRS intervals (166% +/- 36%). Lipid infusion
      exerted a positive inotropic effect, significantly augmenting +dP/dt and systolic
      pressure back to 94% +/- 11% and 102% +/- 16% of baseline in l-bupivacaine
      treated hearts. Heart rate, coronary flow, PR, and QRS intervals remained
      unchanged after lipid intervention. Lipid infusion in paced hearts had a
      significant effect on +dP/dt, systolic pressure, and Mvo2. Neither l-bupivacaine
      nor lipids had an effect on energy charge. A lipid concentration of 500 muL/mL
      plasma was necessary to effect changes in the plasma concentration of local
      anesthetics. CONCLUSION: Lipid application in l-bupivacaine-induced cardiac
      depression had a significant positive inotropic effect, which we would attribute
      to a direct inotropic effect. However, in an isolated heart model, indirect,
      local anesthetic plasma-binding effect of lipids cannot be excluded.

PMID- 17179271
TI  - Lower extremity paralysis after thoracotomy or thoracic epidural: image first,
      ask questions later.
AB  - BACKGROUND: When an epidural catheter is present, new motor deficits will often
      be attributed to a local anesthetic effect, potentially delaying imaging studies,
      or to an epidural hematoma, ignoring other mechanisms of spinal cord injury.
      METHODS: A 69-yr-old female patient undergoing thoracotomy received a
      preoperative thoracic epidural for postoperative analgesia. RESULTS:
      Intraoperatively, there was bleeding near the costovertebral junction. Hemorrhage
      was controlled with cellulose gauze and bone wax. Paralysis developed
      postoperatively and was initially misdiagnosed as a local anesthetic effect when,
      in fact, it was caused by an extradural deposit of cellulose gauze and bone wax.
      CONCLUSIONS: We emphasize the need for prompt, definitive imaging when new lower
      extremity weakness develops after thoracotomy or thoracic epidural analgesia.

PMID- 17179270
TI  - A spray catheter technique for pleural anesthesia: a novel method for pain
      control before talc poudrage.
AB  - BACKGROUND: Chemical pleurodesis causes severe pain, prompting physicians to
      perform thoracoscopic talc poudrage under general or neuroleptanalgesia. We
      describe a novel method for pain control in five patients with pneumothoraces and
      severe chronic obstructive pulmonary disease. METHODS: Patients were premedicated
      with IM pethidine and IV midazolam. The pleural space was examined with the flex
      rigid pleuroscope. Before talc poudrage, 250 mg lidocaine was administered via
      spray catheter, and pain scores measured immediately after the procedure and on
      postoperative days 1 and 2 were 3, 2, and 2, respectively. RESULTS: No
      complications were noted, and 30-day mortality was 0%. CONCLUSION: Lidocaine via
      spray catheter is effective for pain control before pleurodesis.

PMID- 17179269
TI  - The analgesic efficacy of transversus abdominis plane block after abdominal
      surgery: a prospective randomized controlled trial.
AB  - BACKGROUND: The transversus abdominis plane (TAP) block is a novel approach for
      blocking the abdominal wall neural afferents via the bilateral lumbar triangles
      of Petit. We evaluated its analgesic efficacy in patients during the first 24
      postoperative hours after abdominal surgery, in a randomized, controlled, double
      blind clinical trial. METHODS: Thirty-two adults undergoing large bowel resection
      via a midline abdominal incision were randomized to receive standard care,
      including patient-controlled morphine analgesia and regular nonsteroidal
      antiinflammatory drugs and acetaminophen (n = 16), or to undergo TAP block (n =
      16) in addition to standard care (n = 16). After induction of anesthesia, 20 mL
      of 0.375% levobupivacaine was deposited into the transversus abdominis neuro
      fascial plane via the bilateral lumbar triangles of Petit. Each patient was
      assessed by a blinded investigator in the postanesthesia care unit and at 2, 4,
      6, and 24 h postoperatively. RESULTS: The TAP block reduced visual analog scale
      pain scores (TAP versus control, mean +/- sd) on emergence (1 +/- 1.4 vs 6.6 +/-
      2.8, P < 0.05), and at all postoperative time points, including at 24 h (1.7 +/-
      1.7 vs 3.1 +/- 1.5, P < 0.05). Morphine requirements in the first 24
      postoperative hours were also reduced (21.9 +/- 8.9 mg vs 80.4 +/- 19.2 mg, P <
      0.05). There were no complications attributable to the TAP block. All TAP
      patients reported high levels of satisfaction with their postoperative analgesic
      regimen. CONCLUSIONS: The TAP block provided highly effective postoperative
      analgesia in the first 24 postoperative hours after major abdominal surgery.

PMID- 17179272
TI  - Neurologic dysfunction after major thoracic surgery in a patient with severe
      arteriosclerotic disease receiving epidural analgesia.
AB  - We present a patient who underwent pulmonary lobectomy with thoracic epidural
      analgesia and developed postoperative sensory-motor symptoms of the lower limbs.
      Radiological investigation indicated ischemia of the conus medullaris as the
      likely cause. The motor deficit disappeared gradually and the patient was
      mobilizing independently when discharged on postoperative day 21.

PMID- 17179273
TI  - Paravertebral block: the holy grail of anesthesia for hernia surgery?

PMID- 17179274
TI  - Intrathecal catheter granuloma with baclofen infusion.

PMID- 17179275
TI  - Airway injury with low-dose rocuronium versus succinylcholine for rapid-sequence
      induction: relevance and ethics.

PMID- 17179276
TI  - Please don't blame the block ...

PMID- 17179277
TI  - Does the timing of tracheal intubation based on neuromuscular monitoring decrease
      laryngeal injury? Similar method, similar conditions, conflicting results.

PMID- 17179278
TI  - Postoperative analgesia and hospital stay: a call for better study design.

PMID- 17179279
TI  - Conventional endotracheal tubes for intubation through the intubating laryngeal
      mask airway.

PMID- 17179280
TI  - Can we prevent malignant hyperthermia after hypothermic cardiopulmonary bypass in
      a malignant hyperthermia-susceptible patient?

PMID- 17179281
TI  - Does fade with 100-Hz tetanic stimulation reliably detect residual neuromuscular
      blockade?

PMID- 17179282
TI  - Central landmark for central venous catheterization.

PMID- 17179283
TI  - Airway management during second-stage tongue flap procedure.

PMID- 17179284
TI  - Ventilation management during neonatal thoracic surgery.

PMID- 17179285
TI  - Does the N-methyl-d-aspartate receptor contribute to the effects of isoflurane,
      sevoflurane, and ethanol?

PMID- 17179286
TI  - Cricoid pressure is for full stomachs, thyroid pressure is for assisting
      intubations.

PMID- 17179287
TI  - Giant cerebral aneurysm clipping in combination with coronary artery bypass
      graft.

PMID- 17179288
TI  - One-lung ventilation calls for one-lung recruitment.

PMID- 17179289
TI  - Hypoventilation and acute respiratory distress syndrome after radioiodine therapy
      in a patient with thyroid papillary carcinoma and lung metastases.

PMID- 17179290
TI  - A mechanical complication from an anterior mediastinal mass: unusual positioning
      of the central venous catheter.

PMID- 17179291
TI  - Precipitous bispectral index decline and delayed emergence after lumbar puncture.

PMID- 17179292
TI  - Catastrophic hemodynamic changes in a patient with undiagnosed pheochromocytoma
      undergoing abdominal hysterectomy.

PMID- 17179293
TI  - Delayed traumatic right diaphragmatic rupture.

PMID- 17179294
TI  - Stop those hiccups!

PMID- 17179296
TI  - Complications of unrecognized urinary bladder distension.

PMID- 17179295
TI  - Hyperkalemic cardiac arrest with hypertonic mannitol infusion: the strong ion
      difference revisited.

PMID- 17179297
TI  - Infection of a congenital epidural dermoid cyst secondary to lumbar puncture.

PMID- 17179298
TI  - Tracheal intubation with the LMA CTrach or direct laryngoscopy.

PMID- 17179299
TI  - Influence of cisatracurium on entropy values during propofol-remifentanil
      anesthesia.

PMID- 17179300
TI  - Anesthetic implications of a near-lethal sodium azide exposure.

PMID- 17179301
TI  - Large subcutaneous fluid collection attributed to suspected epidural catheter
      leak.

PMID- 17179302
TI  - A severe complication of short-term tracheal intubation.

PMID- 17179304
TI  - Low-dose ketamine analgesia for use in under-developed countries.

PMID- 17179303
TI  - Perioperative management with a dye-densitogram analyzer for a parturient with
      lung edema due to ritodrine toxicity.

PMID- 17179305
TI  - The occurrence of clinical seizure under total intravenous anesthesia for a
      neurosurgical procedure.

PMID- 17179306
TI  - Painful pemphigus vulgaris.

PMID- 17179308
TI  - Delayed recovery from general anesthesia from intracranial tumor.

PMID- 17179307
TI  - Hidden gas leak on a Datex-Ohmeda Aestiva/5 anesthetic machine.

PMID- 17179309
TI  - Surviving sepsis in an adult patient with tetralogy of Fallot.

PMID- 17179310
TI  - Errant thoracic epidural catheterization.

PMID- 17179311
TI  - Exhausted Amsorb Plus CO2 Absorbent Recognized only by Inspired CO2.

PMID- 17179312
TI  - Succinylcholine as an epidural test dose.

PMID- 17179313
TI  - Intraoperative severe anaphylaxis due to gelofusine during a neurosurgical
      procedure.

PMID- 17179314
TI  - Behavioral observations of sleep and anesthesia in the dolphin: implications for
      bispectral index monitoring of unihemispheric effects in dolphins.

PMID- 17179315
TI  - Death after an inadvertent intrathecal injection of tranexamic acid.

PMID- 17179316
TI  - Impact of propofol and etomidate on seizure activity during electroconvulsive
      therapy in patients with schizophrenia.

PMID- 17179317
TI  - Laparoscopic cholecystectomy in an adult with complex-corrected congenital heart
      disease.

PMID- 17179318
TI  - Joint commission on accreditation of healthcare organizations requirements and
      syringe labeling systems.

PMID- 17179319
TI  - Referring physicians' attitudes toward international interpretation of
      teleradiology images.
AB  - OBJECTIVE: We evaluated referring physician attitudes toward the international
      interpretation of radiologic images. MATERIALS AND METHODS: A five-question,
      scenario-based survey describing features of a hypothetic local radiology firm
      compared with those of its hypothetic overseas counterpart, international
      radiology, was sent by mail to 350 physicians from a broad range of medical and
      surgical specialties. One hundred nineteen physicians responded, for a response
      rate of 34%. Referring physicians were asked to indicate their preference for
      local versus international interpretation in each scenario using a 5-point Likert
      scale, with a score of -2 indicating a strong preference for international
      services, 0 indicating no preference, and 2 indicating a strong preference for
      local services. RESULTS: When all variables are held to be equal, referring
      physicians strongly prefer local services (mean score, 1.77; SD, 0.77). When
      international teleradiology provides either a 2-day faster turnaround time for
      reports or a 30 dollars lower out-of-pocket cost to the patient, referring
      physicians still prefer local services, although less than they did with all
      variables held equal (mean score, 0.42-0.44; SD, 1.30-1.40). When international
      teleradiology provides both a 2-day faster turnaround time and a 30 dollars lower
      out-of-pocket cost to the patient, referring physicians preferred international
      teleradiology, albeit only slightly (mean, -0.25; SD, 1.50). Finally, when the
      credentials of the international radiologists are perceived to be less than those
      of the local radiologists, even in the face of faster turnaround time and 30
      dollars lower cost to the patient, referring physicians overall strongly prefer
      local services (mean, 1.51; SD, 0.86). CONCLUSION: Referring physicians prefer
      local interpretation of radiologic images to international interpretation when
      all things are equal. However, the timeliness of image interpretation and the
      cost to the patient are important factors in this decision.

PMID- 17179320
TI  - Radiologic-pathologic conference of the Massachusetts General Hospital. Pulmonary
      hyalinizing granuloma.

PMID- 17179321
TI  - Myocardial bridging of the left anterior descending coronary artery and anomalous
      origin of circumflex coronary artery: preoperative assessment with MDCT.

PMID- 17179322
TI  - Calcified chronic pericardial fat necrosis in localized lipomatosis of
      pericardium.

PMID- 17179323
TI  - CT diagnosis of chyluria after partial nephrectomy.
AB  - OBJECTIVE: The purpose of this study was to describe the CT diagnosis of chyluria
      after partial nephrectomy. CONCLUSION: Fat in the bladder can be identified on CT
      after partial nephrectomy. This finding is caused by chyluria secondary to
      lymphatic injury and should not be mistaken for other abnormalities. Our study
      population did not need treatment of chyluria.

PMID- 17179324
TI  - Development of a cathartic-free colorectal cancer screening test using virtual
      colonoscopy: a feasibility study.
AB  - OBJECTIVE: The purpose of our study was to develop a method to subtract barium
      labeled stool from the colon using a phantom and to evaluate the performance of
      the technique in a pilot human population. MATERIALS AND METHODS: A phantom
      containing 6-mm flat polyps and three types of simulated stool (homogeneous,
      moderately heterogeneous, and severely heterogeneous) mixed with barium was
      created, scanned, and tested using three stool subtraction algorithms but no
      cathartic. Thirty patients with suspected colorectal polyps were studied using
      stool tagging to determine which was the most effective stool subtraction
      algorithm. Colonoscopy was the reference standard. Examinations were evaluated
      blindly using the unsubtracted and 6 weeks later both the unsubtracted and
      subtracted data sets. RESULTS: A threshold of 200 H and expansion and convolution
      techniques were the most effective tools for subtracting stool and minimizing
      artifacts. When applied to the human population, sensitivities using the
      unsubtracted data sets were 90% (18/20) and 68% (26/38) for polyps > or = 1 cm
      and > or = 5 mm, respectively. Specificities were 100% (4/4) and 75% (3/4) for
      polyps > or = 1 cm and > or = 5 mm. For the stool-subtracted data sets,
      sensitivities were 90% (18/20) and 71% (27/38) for polyps > or = 1 cm and > or =
      5 mm. Per patient sensitivities were 88% (15/17) and 77% (20/26) for > or = 1 cm
      and > or = 5 mm polyps. Specificities were 100% (4/4) for large polyps and 25%
      (1/4) for smaller polyps. CONCLUSION: Image processing tools combining
      thresholding, expansion, and convolution were the most useful for stool
      subtraction. Laxative-free colon examinations using barium for stool labeling can
      be performed at CT colonography with or without stool subtraction with high
      accuracy. Further study is warranted.

PMID- 17179325
TI  - High-resolution MRI in evaluation of the surgical anatomy of the esophagus and
      posterior mediastinum.
AB  - OBJECTIVE: The purpose of this study was to use high-resolution MRI to evaluate
      the surgical anatomy of the posterior mediastinum, in particular the esophagus
      and its relation to the surrounding structures. The aim was to familiarize
      radiologists with the appearance of structures considered important in planning
      surgical resection of the esophagus. MATERIALS AND METHODS: The thoraces of two
      cadavers were imaged with a 1.5-T magnet using a high-resolution T2-weighted
      sequence. Axial cadaveric sections of the posterior mediastinum were cut with a
      band saw at levels determined from the MR images, and histologic whole-mount
      sections of the esophagus and surrounding tissue were prepared from the cadaveric
      sections. The appearance of structures identified on the MR images was compared
      with the findings on corresponding gross anatomic and histologic whole-mount
      sections. RESULTS: The MR images depicted the esophagus and structures in close
      anatomic relation: the pleural reflections and pericardium. The technique enabled
      visualization of structures to our knowledge not previously described on cross
      sectional imaging: the individual layers of the esophageal wall, the thoracic
      duct, a connective tissue layer attaching the esophagus to the anterior wall of
      the aorta, and a fascial plane passing between layers of the right and left
      parietal pleura posterior to the esophagus. CONCLUSION: High-resolution MRI of
      the posterior mediastinum provides detailed anatomic information, delineating
      structures not visible on other forms of cross-sectional imaging. It can provide
      important information for planning surgical intervention.

PMID- 17179326
TI  - Biliary inflammatory pseudotumor: imaging features in seven patients.
AB  - OBJECTIVE: Hepatic biliary pseudotumor is a benign, rare, and poorly understood
      tumor that is typically diagnosed after aggressive surgical intervention. The
      purpose of this report is to describe the clinical and imaging features of this
      tumor in seven patients. CONCLUSION: Although secondary clinical features may
      rarely suggest inflammatory pseudotumor, the typical presenting symptom--painless
      obstructive jaundice--is indicative of malignancy. The imaging appearance of
      hepatic hilar biliary pseudotumor is also indistinguishable from that of
      cholangiocarcinoma.

PMID- 17179327
TI  - Hepatic MRI using the double-echo chemical shift phase-selective gradient-echo
      technique.
AB  - OBJECTIVE: The objective of our study was to describe the merits and drawbacks of
      the double-echo chemical shift phase-selective gradient-echo technique for
      hepatic MRI. CONCLUSION: With complementary information from two different
      dynamic imaging sets in conjunction with errorless subtraction between in- and
      out-of-phase images, the double-echo chemical shift phase-selective gradient-echo
      technique provides useful information regarding unpredictable variations in intra
      or extralesional lipid content, allowing detailed assessment of focal lesions
      during hepatic MRI.

PMID- 17179328
TI  - CT findings of rupture, impending rupture, and contained rupture of abdominal
      aortic aneurysms.
AB  - OBJECTIVE: With the increasing use of cross-sectional imaging for a variety of
      medical and surgical conditions affecting the abdomen and pelvis, familiarity
      with the imaging features of aneurysm rupture--and the findings suspicious for
      impending or contained aneurysm rupture--is crucial for all radiologists. This
      pictorial essay will review the imaging findings of rupture of abdominal aortic
      aneurysms and of complicated aneurysms. CONCLUSION: Prompt detection of abdominal
      aortic aneurysm rupture or impending rupture is critical because emergent surgery
      may be required and patient survival may be at stake.

PMID- 17179329
TI  - Musculoskeletal sonography: a dynamic tool for usual and unusual disorders.
AB  - OBJECTIVE: The purpose of this study is to illustrate a wide variety of
      musculoskeletal disorders that can be diagnosed with dynamic sonography.
      CONCLUSION: Dynamic sonography is a useful tool for the evaluation of a variety
      of musculoskeletal disorders. Many of these disorders cannot be diagnosed by any
      other imaging method.

PMID- 17179330
TI  - Neuroimaging strategies for three types of Horner syndrome with emphasis on
      anatomic location.
AB  - OBJECTIVE: The purposes of this study were to review the anatomy of the
      oculosympathetic pathway, to describe the clinical characteristics of the three
      types of Horner syndrome, and to illustrate underlying pathologic features with
      an emphasis on neuroimaging strategies based on three symptom complexes.
      CONCLUSION: Horner syndrome results from interruption of the oculosympathetic
      pathway and is usually associated with unique clinical features classified into
      central, preganglionic, and postganglionic types according to the anatomic
      location of the underlying pathologic process.

PMID- 17179331
TI  - Prenatal tracheal obstruction due to double aortic arch: a potential mimic of
      congenital high airway obstruction syndrome.

PMID- 17179332
TI  - High-resolution sonography for nasal fracture in children.
AB  - OBJECTIVE: We describe the sonographic findings of nasal fracture in children,
      and we evaluate the diagnostic value of sonography as compared with conventional
      radiography and clinical findings to determine whether sonography can be a
      primary technique for evaluating nasal fracture in children. MATERIALS AND
      METHODS: Conventional radiographs and sonographic scans were obtained in 26
      consecutive children with nasal trauma who were seen at our hospital from March
      2003 to March 2005. There were five girls and 21 boys, and their ages ranged from
      1 year 9 months to 15 years 11 months (mean age, 9.9 years). The following
      sonographic scans (HDI-5000 unit with a 7-15-MHz linear array transducer) were
      used to evaluate the nasal bone at different levels: a midline longitudinal
      image; axial scans of the nasal bones at the upper, middle, and lower levels;
      images of the nasal septum; and transverse and longitudinal scans of both lateral
      walls. Ten children also underwent CT. RESULTS: Conventional radiographs depicted
      14 (54%) of 26 fractures. Sonographic scans were able to show all the fracture
      lines. One case was diagnosed as an old nasal fracture on the basis of a physical
      examination, even though a visible fracture line was seen on sonography. The
      sonographic findings of nasal fracture were disruption of the bone continuity
      with or without separation of the fractured segment (7/26), displacement of the
      bone segment as being depressed or overriding (20/26), associated septal
      deviation (7/26), and separation of the pyriform aperture of the maxilla and
      nasal bone (2/26). The associated findings were soft-tissue edema and hypoechoic
      hematoma near the fracture lines in 25 cases. The fractures involved both sides
      of the nasal bones in 11 of 26 cases, the midline part of the bones in six of 26
      cases, and the unilateral paramedian or lateral part of the bones in 12 of 26
      cases. Among the 10 CT scans, one CT scan did not depict the fracture, showing
      only soft-tissue swelling, and one scan showed fractures of the orbital floor and
      maxilla. CONCLUSION: Sonography can be a primary diagnostic technique for
      evaluating nasal fracture in children. It inflicts no radiation, provides various
      imaging planes without positional change, and can be used to evaluate the
      cartilaginous septum. Potential pitfalls are the nasofrontal suture, the junction
      between the nasal bone and the pyriform aperture of the maxilla, the vascular
      groove, and the presence of an old fracture. CT can be used in addition to
      sonography in cases of suspected complex facial bone trauma.

PMID- 17179333
TI  - Preclinical medical student training in radiology: the effect of early exposure.
AB  - OBJECTIVE: The purpose of this study was to determine whether an integrated
      radiology curriculum in the first year of medical school changes medical
      students' attitudes toward radiology or affects their knowledge of radiologic
      principles. SUBJECTS AND METHODS: The first-year medical curriculum of a medical
      school was revised between the 2003 and 2004 academic years to introduce more
      didactic radiology teaching. Dedicated radiology lectures were introduced, and
      radiology consult sessions became integral to problem-based learning sessions. A
      survey was administered between the first and second years of training to assess
      first-year medical students' attitudes toward radiology and their knowledge of
      basic radiologic principles. Students who had undertaken the revised curriculum
      (class of 2008) were compared with students who had undertaken the traditional
      curriculum (class of 2007). Survey responses were compared with Mann-Whitney rank
      sum tests. RESULTS: Students exposed to the new curriculum stated that they were
      more familiar with radiology as a specialty and believed that radiology had
      greater importance to the overall practice of medicine. They stated that they
      were more likely to select radiology as a clinical elective, and more of them
      were considering radiology as a career option. The students who had been exposed
      to radiology performed better on the test of basic radiologic knowledge. All
      results were statistically significant. CONCLUSION: Exposing students to
      radiology in the first year of medical school improves their impression of
      radiology as a specialty and increases their interest in radiology as a career.
      Follow-up surveys will determine whether this effect persists through the
      clinical years of training and improves the overall impression of radiology
      within the medical community.

PMID- 17179334
TI  - Identification of severe left main trunk coronary stenosis on MDCT coronary
      angiography.

PMID- 17179335
TI  - MRI of diabetic cheiroarthropathy.

PMID- 17179336
TI  - Simple method to eliminate camera reflections in digital photographs of single
      emulsion films.

PMID- 17179337
TI  - Hyperbaric oxygen therapy for arterial air embolism.

PMID- 17179338
TI  - Major changes in radiology residency program requirements are coming.

PMID- 17179339
TI  - Commentary on "Major changes in radiology residency program requirements are
      coming".

PMID- 17179340
TI  - Morphology predicts oncology: a commentary on Vezina and Sutton's article,
      "Prolactin-secreting pituitary microadenomas: roentgenologic diagnosis".

PMID- 17179341
TI  - Imaging of angiogenesis: clinical techniques and novel imaging methods.
AB  - OBJECTIVE: A wide variety of antiangiogenic agents have been developed for the
      treatment of neoplasms. Imaging studies play an important role in assessing the
      effects of these treatments. CONCLUSION: This review article introduces
      radiologists to features of these therapies and the most important clinical and
      preclinical imaging techniques for evaluating antiangiogenic agents.

PMID- 17179342
TI  - Dynamic MRI of solitary pulmonary nodules: comparison of enhancement patterns of
      malignant and benign small peripheral lung lesions.
AB  - OBJECTIVE: The purpose of this study was to compare the dynamic contrast-enhanced
      MRI enhancement characteristics of malignant and benign solitary pulmonary
      nodules. MATERIALS AND METHODS: The characteristics of 202 solitary pulmonary
      nodules (diameter, 1-3 cm; 144 cases of primary lung cancer, 31 cases of focal
      organizing pneumonia, 15 tuberculomas, 12 hamartomas) were reviewed
      retrospectively. In all cases dynamic MR images were obtained before and 1, 2, 3,
      4, 5, 6, and 8 minutes after bolus injection of gadopentetate dimeglumine.
      Maximum enhancement ratio, time at maximum enhancement ratio, slope of time
      enhancement ratio curves, and washout ratio were assessed. Statistical analyses
      were performed with the Kruskal-Wallis test with Bonferroni correction, chi
      square test, and receiver operating characteristic curves. RESULTS: For 122 (85%)
      of 144 primary lung cancers, time at maximum enhancement ratio was 4 minutes or
      less. For all tuberculomas and hamartomas, time at maximum enhancement ratio was
      greater than 4 minutes or gradual enhancement occurred without a peak time (p <
      0.0001). Lung cancers had different maximum enhancement ratios and slopes than
      benign lesions (all p < 0.005). With 110% or lower maximum enhancement ratio as a
      cutoff value, the positive predictive value for malignancy was 92%; sensitivity,
      63%; and specificity, 74%. With 13.5%/min or greater slope as a cutoff value,
      sensitivity, specificity, positive predictive value, and negative predictive
      value for malignancy were 94%, 96%, 99%, and 74%, respectively. CONCLUSION:
      Dynamic contrast-enhanced MRI is helpful in differentiating benign from malignant
      solitary pulmonary nodules. Absence of significant enhancement is a strong
      predictor that a lesion is benign.

PMID- 17179343
TI  - Accuracy of transthoracic sonography in detection of pneumothorax after
      sonographically guided lung biopsy: prospective comparison with chest
      radiography.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate the accuracy
      of transthoracic sonography in the detection of pneumothorax after transthoracic
      sonographically guided lung biopsy. SUBJECTS AND METHODS: Transthoracic
      sonography was performed on 285 patients after transthoracic sonographically
      guided lung biopsy. Disappearance of the sliding lung and comettail artifacts and
      appearance of reverberation artifacts were considered evidence of pneumothorax.
      Upright chest radiography was performed within 30 minutes of transthoracic
      sonography. If a discrepancy between transthoracic sonographic and chest
      radiographic findings occurred, CT was performed. When it was diagnosed,
      pneumothorax was sonographically monitored. After visualization of resolution of
      pneumothorax, chest radiography was performed to confirm the resolution. RESULTS:
      Pneumothorax occurred in eight (2.8%) of the patients. Transthoracic sonography
      depicted all cases of pneumothorax and excluded pneumothorax in the other cases.
      Chest radiography did not depict one case of pneumothorax, which was confirmed on
      CT. Sensitivity, specificity, positive predictive value, negative predictive
      value, and overall accuracy were all 100% for transthoracic sonography and 87.5%,
      100%, 100%, 99.6%, and 99.6%, respectively, for chest radiography. The 95%
      confidence intervals (CI) of the differences in sensitivity, negative predictive
      value, and overall accuracy were -10% to 35%, -0.1 to 0.9%, and -0.1 to 0.9%.
      Transthoracic sonographic visualization of resolution of pneumothorax was always
      confirmed with chest radiography. CONCLUSION: These preliminary results suggest
      that transthoracic sonography is as effective as chest radiography in the
      detection of pneumothorax after transthoracic sonographically guided lung biopsy
      and may become the method of choice for excluding, diagnosing, and monitoring
      pneumothorax after transthoracic sonographically guided biopsy. Chest radiography
      may be needed only for assessment of the extent of pulmonary collapse after
      transthoracic sonographic diagnosis of pneumothorax or in the presence of
      discrepancy between transthoracic sonographic findings and clinical presentation.

PMID- 17179344
TI  - Comparison of standard- and low-radiation-dose CT for quantification of
      emphysema.
AB  - OBJECTIVE: This study was performed to compare standard- and low-radiation-dose
      techniques in the CT quantification of emphysema. MATERIALS AND METHODS: The
      study population consisted of 36 men and 20 women who were current or former
      heavy smokers and underwent standard-dose (effective tube current, 100-250 mAs)
      chest CT at our institution within 6 months of having undergone low-dose
      (effective tube current, 30-60 mAs) chest CT. All CT scans were reconstructed at
      5-mm slice thickness with a smooth filter. CT-measured lung volume, mean and
      median lung attenuation, and percentage of lung volume with attenuation lower
      than multiple thresholds (emphysema index values) were compared by Pearson
      correlation, two-tailed and paired Student's t tests, and regression analysis.
      RESULTS: There were no significant differences in mean attenuation (-848 vs -846
      H, p > 0.35) for the low dose and the standard dose or in median lung attenuation
      (-879 vs -878 H, p > 0.66). Low- and standard-dose emphysema indexes were
      correlated at all attenuation thresholds (r = 0.86-0.97). Mean emphysema indexes
      were higher on the low-dose scans, but the mean difference at all thresholds was
      less than 3%. The differences were significant (p < 0.05) only at the lower index
      thresholds, correlated with differences in lung volume (r < or = 0.86), and
      increased with greater differences in dose. CONCLUSION: Low-dose technique has
      minimal effect on CT quantification of emphysema.

PMID- 17179345
TI  - Primary pulmonary hypertension: 3D dynamic perfusion MRI for quantitative
      analysis of regional pulmonary perfusion.
AB  - OBJECTIVE: The purpose of this study was to determine whether quantitative
      pulmonary perfusion parameters obtained from 3D dynamic contrast-enhanced MR
      perfusion data can be used to assess the severity of primary pulmonary
      hypertension (PPH) as indicated by pulmonary vascular resistance (PVR) and mean
      pulmonary artery pressure (MPAP). CONCLUSION: Three-dimensional dynamic contrast
      enhanced MRI has potential for assessment of disease severity as indicated by PVR
      and MPAP in patients with PPH.

PMID- 17179346
TI  - Solitary pulmonary nodules: detection, characterization, and guidance for further
      diagnostic workup and treatment.
AB  - OBJECTIVE: The purpose of our study is to improve radiologists' understanding of
      the clinical issues involved in making a diagnosis and to guide further
      diagnostic workup and treatment of solitary pulmonary nodules (SPNs). CONCLUSION:
      Information on the morphologic and hemodynamic characteristics of SPNs provided
      by dynamic helical CT, with high specificity and reasonably high accuracy, can be
      used for initial assessment. PET/CT is more sensitive at detecting malignancy
      than dynamic helical CT, and all malignant nodules may be potentially diagnosed
      as malignant by both techniques. Therefore, PET/CT may be selectively performed
      to characterize SPNs that show indeterminate results at dynamic helical CT.

PMID- 17179347
TI  - MRI of the coronary vessel wall at 3 T: comparison of radial and cartesian k
      space sampling.
AB  - OBJECTIVE: The purpose of our study was to compare the quality of 3D gradient
      echo images obtained using radial versus cartesian k-space sampling at 3 T.
      CONCLUSION: This study shows that the quality of coronary vessel wall imaging of
      the right coronary artery with radial k-space sampling in 3D turbo field-echo
      sequences is superior to cartesian k-space sampling at 3 T. Radial k-space
      sampling at 3 T makes it possible to combine low motion artifact susceptibility
      with high signal-to-noise ratio.

PMID- 17179348
TI  - ECG-gated 64-MDCT angiography in the differential diagnosis of acute chest pain.
AB  - OBJECTIVE: The most important differential diagnoses of acute chest pain include
      myocardial infarction, aortic dissection, and pulmonary embolism. The purpose of
      this study was to evaluate the diagnostic value of an ECG-gated 64-MDCT
      angiography protocol for simultaneous assessment of the pulmonary arteries,
      coronary arteries, and aorta within a single breath-hold. SUBJECTS AND METHODS:
      In 55 patients with acute chest pain, ECG-gated CT angiography was performed with
      a CT system in which 64 slices per gantry rotation were acquired. Density
      measurement and visual assessment of motion artifacts were performed to evaluate
      image quality. CT findings were correlated with results of laboratory tests and
      clinical follow-up. For 20 patients, two independent blinded reviewers compared
      findings on CT angiography with those on X-ray coronary angiography. RESULTS:
      Adequate contrast enhancement of the pulmonary vessels, coronary arteries, and
      aorta was achieved in all cases. Regarding image quality of the coronary
      arteries, there was minor blurring in seven patients, and in one examination the
      images did not provide enough information for diagnosis. The average image
      quality rating was 1.2 on a scale in which 1 indicated no artifacts; 2, minor
      motion artifacts; and 3, image insufficient for diagnosis. The cause of chest
      pain was correctly identified with MDCT in 37 patients. The diagnoses included
      pulmonary embolism (n = 10), coronary stenosis (n = 9), and aortic dissection (n
      = 1). In four patients, additional diagnoses were found with other examinations.
      CONCLUSION: With current techniques, ECG-gated CT angiography of the entire chest
      has very good image quality. The protocol proved helpful in the differential
      diagnosis of acute chest pain.

PMID- 17179349
TI  - Per-sextant localization and staging of prostate cancer: correlation of imaging
      findings with whole-mount step section histopathology.
AB  - OBJECTIVE: The objective of our study was to determine the diagnostic accuracy
      and interobserver agreement of 1.5-T prostatic MRI for per-sextant tumor
      localization and staging of prostate cancer as compared with whole-mount step
      section histopathology. MATERIALS AND METHODS: Combined endorectal-pelvic phased
      array prostatic MRI scans obtained at 1.5 T of 106 patients with biopsy-proven
      prostate cancer who had undergone radical prostatectomy with whole-mount step
      section histopathology within 28 days of MRI were retrospectively analyzed by
      three independent abdominal radiologists (reviewers 1, 2, and 3). Sextants of the
      prostate (right and left base, middle, and apex) were evaluated for the presence
      of prostate cancer and extracapsular extension (ECE) using a 5-point confidence
      scale. Data were statistically analyzed using receiver operating characteristic
      (ROC) analysis. Interobserver variability was assessed by kappa statistics. For
      calculation of sensitivity and specificity, data from the 5-point confidence
      scale were dichotomized into negative (score of 1-3) or positive (score of 4 or
      5) findings. RESULTS: Forty-one patients had ECE (tumor stage T3), and 65
      patients had organ-confined disease (stage T2). Of 636 prostatic sextants, 417
      were positive for prostate cancer and 135 were positive for ECE at
      histopathology. For prostate cancer localization, ROC analysis yielded area under
      the ROC curve (AUC) values ranging from 0.776 +/- 0.023 (SD) to 0.832 +/- 0.027.
      For the detection of ECE, the AUC values ranged from 0.740 +/- 0.054 to 0.812 +/-
      0.045. Interobserver agreement (kappa) ranged from 0.49 to 0.60 for prostate
      cancer localization and from 0.59 to 0.67 for the detection of ECE. CONCLUSION:
      Using the sextant framework, independent observers reach similar accuracy with
      moderate to substantial agreement for the localization of prostate cancer and ECE
      by means of MRI of the prostate.

PMID- 17179350
TI  - Combined use of diffusion-weighted MRI and 1H MR spectroscopy to increase
      accuracy in prostate cancer detection.
AB  - OBJECTIVE: The objective of our study was to establish the sensitivity and
      specificity for prostate cancer detection using a combined 1H MR spectroscopy and
      diffusion-weighted MRI approach. SUBJECTS AND METHODS: Forty-two men (mean age +/
      SD, 69.3 +/- 4.7 years) with prostate cancer were studied using endorectal T2
      weighted imaging, 2D chemical shift imaging (CSI), and isotropic apparent
      diffusion coefficient (ADC) maps. Regions of interest (ROIs) were drawn around
      the entire gland, central gland, and peripheral zone tumor, diagnostically
      defined as low signal intensity on T2-weighted images within a sextant that was
      biopsy-positive for tumor. Lack of susceptibility artifact on a gradient-echo B0
      map through the slice selected for CSI and no high signal intensity on external
      array T1-weighted images confirmed the absence of significant hemorrhage after
      biopsy. CSI voxels were classified as nonmalignant or as tumor (ROI included > or
      = 30% or > or = 70% tumor). Choline-citrate (Cho/Cit) ratios and average ADCs
      were calculated for every voxel. A plot of Cho/Cit ratios versus ADCs yielded a
      line of best separation of tumor voxels from nonmalignant voxels. Receiver
      operating characteristic (ROC) curves were plotted for Cho/Cit ratios alone, ADCs
      alone, and a combination of the two. RESULTS: The Cho/Cit ratios were
      significantly higher (p < 0.001) and the ADCs were significantly lower (p <
      0.006) in tumor-containing voxels than in non-tumor-containing voxels. When
      voxels containing 30% or more tumor were considered positive, the area under the
      ROC curves using combined MR spectroscopy and ADC (0.81) was similar to that of
      Cho/Cit alone (0.79) and better than ADC alone (0.66). When voxels containing 70%
      or more tumor were considered positive and cutoffs to achieve a 90%-or-greater
      sensitivity chosen, a combination of Cho/Cit and ADC achieved a significant
      improvement in specificity compared with Cho/Cit alone (p < 0.0001) or ADC alone
      (p < 0.0001). CONCLUSION: When voxels containing > or = 70% tumor are considered
      positive, the combined use of MR spectroscopy and diffusion-weighted MRI
      increases the specificity for prostate cancer detection while retaining the
      sensitivity compared with MR spectroscopy alone or diffusion-weighted MRI alone.

PMID- 17179351
TI  - Incremental value of multiplanar cross-referencing for prostate cancer staging
      with endorectal MRI.
AB  - OBJECTIVE: The purpose of this study was to assess whether use of the PACS cross
      referencing tool in 3D MRI improves tumor staging of prostate cancer when
      pathologic findings are used as the reference standard. MATERIALS AND METHODS:
      The institutional review board granted a waiver of informed consent for the
      study. Endorectal MRI at 1.5 T was performed before radical prostatectomy in 255
      consecutive patients. Two radiologists unaware of the clinical data
      retrospectively and independently interpreted MR images without and with cross
      referencing to predict the presence of extracapsular extension (ECE) and seminal
      vesicle invasion (SVI). Histopathologic findings were used as the reference
      standard. Area under the receiver operating characteristics curve (AUC),
      sensitivity and specificity, and weighted kappa statistics were calculated.
      RESULTS: At histologic examination, 68 (27%) of the patients were found to have
      ECE and 13 (5%) of the patients to have SVI; the latter all had ECE. In detecting
      ECE, both reviewers had a higher AUC using cross-referencing (p < 0.001 for
      both). The weighted kappa value was 0.56 for MRI alone and 0.76 for MRI with
      cross-referencing, indicating fair to good interobserver agreement. Sensitivity
      and specificity for ECE with MRI alone and with cross-referencing were 43% and
      94% and 57% and 100% for reviewer 1 and 40% and 93% and 59% and 98% for reviewer
      2, respectively. In detecting SVI, both reviewers had a higher AUC with cross
      referencing (p = 0.007 and p = 0.056 for reviewers 1 and 2, respectively).
      Reviewer 1 benefited much more from cross-referencing than did reviewer 2. The
      weighted kappa statistic was 0.69 for MRI alone and the same with cross
      referencing, indicating good interobserver agreement. Sensitivity and specificity
      for SVI with MRI alone and with cross-referencing, respectively, were 23% and 83%
      and 46% and 93% for reviewer 1 and 31% and 91% and 54% and 95% for reviewer 2.
      CONCLUSION: PACS cross-referencing significantly improves tumor staging of
      prostate cancer with 3D MRI. Some reviewers benefit more than others from use of
      this tool.

PMID- 17179352
TI  - Surgically relevant normal and variant renal parenchymal and vascular anatomy in
      preoperative 16-MDCT evaluation of potential laparoscopic renal donors.
AB  - OBJECTIVE: Using 16-MDCT, we describe and quantify the frequency and types of
      renal anatomic variants and findings relevant for preoperative evaluation and
      surgical planning for potential laparoscopic renal donors. MATERIALS AND METHODS:
      On 16-MDCT, 126 consecutive potential donors underwent scanning before contrast
      administration and after i.v. power injection of nonionic contrast material
      during the arterial, nephrographic, and excretory phases. On a 3D workstation, CT
      images were evaluated retrospectively in consensus by three abdominal imagers.
      The number and branching pattern of bilateral renal arteries and veins, including
      anomalies of the inferior vena cava and lumbar-gonadal axis, were categorized
      along with the frequency of incidental findings of the renal parenchyma and
      collecting system. RESULTS: Major arterial variants including supernumerary and
      early branching arteries were present in 16% and 21%, respectively, of left
      kidneys and 22% and 15%, respectively, of right kidneys. Major and minor venous
      variants were detected in 11% and 58% of left kidneys and 24% and 3% of right
      kidneys. Late confluence of the venous trunk was identified in 17% of left
      kidneys and 10% of right kidneys. Incidental parenchymal and urothelial
      abnormalities, most commonly cysts and calyceal calcifications, were identified
      in 30% of the kidneys. Other relevant incidental findings included focal
      infarcts, cortical scars, atrophic scarred kidney, and bilateral papillary
      necrosis. Urothelial variants included bilateral simple ureteroceles and
      rightsided complete duplicated collecting system. CONCLUSION: 16-MDCT angiography
      and urography allow confident detection and classification of a variety of
      anatomic and incidental anomalies relevant to the preoperative selection of
      potential laparoscopic renal donors and to surgical planning.

PMID- 17179353
TI  - 16-MDCT angiography in living kidney donors at various tube potentials: impact on
      image quality and radiation dose.
AB  - OBJECTIVE: The objective of our study was to compare the performance of 16-MDCT
      angiography at various peak kilovoltage (kVp) settings and the impact of the
      different settings on image quality and on radiation dose in adult kidney donors.
      MATERIALS AND METHODS: Sixty-two renal donors (32 men, 30 women) who underwent 16
      MDCT were divided into three groups: 18 subjects were studied at 140 kVp (group
      A); 20, at 120 kVp (group B); and 24, at 100 kVp (group C). Other constant
      scanning parameters were as follows: detector collimation, 0.625 mm; table feed,
      9.375 mm/rotation; gantry rotation time, 500 milliseconds; and automatic current
      tube modulation (ATCM) using a noise index of 15. A total of 135-140 mL of
      iodinated contrast material (300 mg I/mL) was administered at 5 mL/s via an 18
      gauge cannula, and arterial phase scanning was initiated using a bolus-tracking
      technique. Two observers evaluated image quality of the axial and 3D images and
      the visibility of branch order in the superior mesenteric artery (SMA) and renal
      arteries. Attenuation (in Hounsfield units [H]) in the aorta, SMA, and main renal
      artery was also measured by placing a region of interest. Radiation dose
      measurements were based on the scanner-generated CT dose index volume
      (CTDI(vol)). Each parameter tested was compared among the three groups using a
      nonparametric analysis of variance test, and a p value of 0.05 was considered
      significant. RESULTS: Differences in the quality of the axial images existed
      between groups A and C (p < 0.001) and between groups B and C (p < 0.01); the
      image quality of the 3D images and the visibility of branch order in the SMA and
      renal arteries were comparable for all groups. The difference in mean attenuation
      of the aorta, SMA, and renal arteries was significant between groups A and C (p <
      0.001) and between groups B and C (p < 0.01). All groups had 100% diagnostic
      accuracy in identifying the number of renal arteries on the side of nephrectomy.
      The mean radiation dose in CTDI(vol) was 25 +/- 3 mGy at 140 kVp, 17 +/- 4 mGy at
      120 kVp, and 12 +/- 3 mGy at 100 kVp (p < 0.001). CONCLUSION: Our initial
      observations suggest that the image quality of 16-MDCT angiography performed at
      120 kVp is similar to that of CT angiography (CTA) performed at 140 kVp in adult
      kidney donors but with a significant radiation dose reduction. CTA at 100 kVp
      results in higher image noise but provides diagnostically acceptable images with
      significant radiation dose reduction compared with CTA at 120 or 140 kVp.

PMID- 17179354
TI  - Polyp measurement with CT colonography: multiple-reader, multiple-workstation
      comparison.
AB  - OBJECTIVE: The risk of invasive colorectal cancer in colorectal polyps correlates
      with lesion size. Our purpose was to define the most accurate methods for
      measuring polyp size at CT colonography (CTC) using three models of workstations
      and multiple observers. MATERIALS AND METHODS: Six reviewers measured 24 unique
      polyps of known size (5, 7, 10, and 12 mm), shape (sessile, flat, and
      pedunculated), and location (straight or curved bowel segment) using CTC data
      sets obtained at two doses (5 mAs and 65 mAs) and a previously described colonic
      phantom model. Reviewers measured the largest diameter of polyps on three
      proprietary workstations. Each polyp was measured with lung and soft-tissue
      windows on axial, 2D multiplanar reconstruction (MPR), and 3D images. RESULTS:
      There were significant differences among measurements obtained at various
      settings within each workstation (p < 0.0001). Measurements on 2D images were
      more accurate with lung window than with soft-tissue window settings (p <
      0.0001). For the 65-mAs data set, the most accurate measurements were obtained in
      analysis of axial images with lung window, 2D MPR images with lung window, and 3D
      tissue cube images for Wizard, Advantage, and Vitrea workstations, respectively,
      without significant differences in accuracy among techniques (0.11 < p < 0.59).
      The mean absolute error values for these optimal settings were 0.48 mm, 0.61 mm,
      and 0.76 mm, respectively, for the three workstations. Within the ultralow-dose 5
      mAs data set the best methods for Wizard, Advantage, and Vitrea were axial with
      lung window, 2D MPR with lung window, and 2D MPR with lung window, respectively.
      Use of nearly all measurement methods, except for the Vitrea 3D tissue cube and
      the Wizard 2D MPR with lung window, resulted in undermeasurement of the true size
      of the polyps. CONCLUSION: Use of CTC computer workstations facilitates accurate
      polyp measurement. For routine CTC examinations, polyps should be measured with
      lung window settings on 2D axial or MPR images (Wizard and Advantage) or 3D
      images (Vitrea). When these optimal methods are used, these three commercial
      workstations do not differ significantly in acquisition of accurate polyp
      measurements at routine dose settings.

PMID- 17179355
TI  - Combined CT colonography and 18F-FDG PET of colon polyps: potential technique for
      selective detection of cancer and precancerous lesions.
AB  - OBJECTIVE: The purpose of this study was to determine the feasibility of imaging
      the colon with fused CT colonography (CTC) and 18F-FDG PET and to correlate the
      findings with the histologic features of polyps. SUBJECTS AND METHODS: Eighteen
      patients with suspected colorectal polyps enrolled in this prospective study.
      Before colonoscopy, 17 of the patients underwent a combination of FDG PET and
      CTC. CTC consisted of 4-MDCT merged with PET. PET of the abdomen and pelvis was
      performed after each CTC scan. One radiologist and one nuclear medicine physician
      in consensus analyzed PET and CTC fusion data. PET standard uptake value was
      correlated with the findings at histologic examination of polyps. Patient
      feasibility was defined as the ability to tolerate prolonged scanning with good
      colonic distention. Technical feasibility was determined by how closely
      anatomically matched polyps overlapped on fusion images. RESULTS: Seventeen of 18
      patients tolerated scanning. Eighty-five percent of colon segments were optimally
      distended. Twenty-three of 27 FDG-avid polyps measuring 10 mm or more had
      excellent overlap at fusion imaging. PET depicted 23 of 39 premalignant polyps
      and even showed increased tracer activity associated with four small tubular
      adenomas (4-6 mm). Sixteen benign polyps (10-25 mm) were not depicted on PET. All
      nine cases of cancer (tumors measuring 11-60 mm) were detected with both PET and
      CTC. The standard uptake value of malignant tumors ranged from 4 to 20 (mean, 9).
      However, six benign flat polyps did not exhibit FDG avidity. CONCLUSION: The
      novel combination of CTC and PET was feasible in 17 of 18 patients and allowed
      excellent image correlation in 23 of 27 proven polyps measuring 10 mm or more on
      PET-CTC fusion. This technique shows promise in accurate anatomic correlation of
      both malignant and premalignant lesions evaluated with FDG PET.

PMID- 17179356
TI  - Esophageal varices in cirrhotic patients: evaluation with liver CT.
AB  - OBJECTIVE: The objective of this study was to evaluate the performance of routine
      helical liver CT in the detection and grading of esophageal varices in cirrhotic
      patients. MATERIALS AND METHODS: A total of 67 consecutive cirrhotic patients who
      underwent both upper endoscopy and helical liver CT within a 4-week interval were
      evaluated. The CT protocol included unenhanced, arterial, and portal phases with
      a collimation of 7-7.5 mm. Two blinded abdominal imagers (6 and 7 years'
      experience) retrospectively interpreted all CT images to detect the presence of
      esophageal varices on a 5-point confidence scale and measure the largest varix
      identified. Receiver operating characteristic (ROC) curve analysis was performed,
      and the correlation between CT measurements and endoscopic grading, the reference
      standard, was assessed. RESULTS: The variceal detection rates for the observers
      was 92% (11/12) and 92% (11/12) for large (i.e., clinically significant) varices,
      53% (16/30) and 60% (18/30) for small varices, and 64% (27/42) and 69% (29/42)
      for all varices. The area under the ROC curve for the detection of esophageal
      varices of any size was 0.77 (observer 1) and 0.80 (observer 2). CT variceal
      grading showed a strong correlation with endoscopic grading for both observers (p
      < or = 0.001). Using a variceal diameter threshold of 3 mm on CT, sensitivity,
      specificity, and accuracy for distinguishing large esophageal varices from small
      or no varices were 92% (11/12), 84% (46/55), and 85% (57/67), respectively, for
      both observers. CONCLUSION: Liver CT is useful for the detection and grading of
      esophageal varices. A diameter of 3 mm may be an appropriate screening threshold
      for large clinically significant varices.

PMID- 17179357
TI  - Dynamic CT for detecting small hepatocellular carcinoma: usefulness of delayed
      phase imaging.
AB  - OBJECTIVE: The purpose of this retrospective study was to determine the
      usefulness of delayed phase imaging for detecting small (< or = 2 cm)
      hepatocellular carcinomas (HCCs) in patients with liver cirrhosis. MATERIALS AND
      METHODS: Triphasic (arterial, portal venous, and delayed phases) dynamic CT was
      performed in 33 patients with 48 HCCs proven histopathologically and in 65
      control subjects. Arterial, portal venous, and delayed phase images were obtained
      30 seconds, 68-70 seconds, and 5 minutes after the start of contrast material
      injection, respectively. Three blinded observers reviewed the images
      independently and evaluated tumor attenuation. Diagnostic performance for the
      combination of phases was assessed using receiver operating characteristic (ROC)
      curve analysis. RESULTS: On arterial phase images, 28 of the 48 HCCs were
      hyperattenuating, nine were isoattenuating, and 11 were hypoattenuating. On
      portal venous phase images, three tumors were hyperattenuating, 17 were
      isoattenuating, and 28 were hypoattenuating. On delayed phase images, five tumors
      were isoattenuating, and 43 were hypoattenuating. The mean sensitivity for the
      combination of arterial and portal venous phase imaging was 86.8%, that for the
      combination of arterial and delayed phase imaging was 90.3%, and that for the
      combination of all three phase imaging was 93.8%. The area underneath composite
      ROC curve (A(Z)) for the combination of all three phase imaging (A(Z) = 0.940)
      was significantly higher than that for the combination of arterial and portal
      venous phase imaging (A(Z) = 0.917) and for the combination of arterial and
      delayed phase imaging (A(Z) = 0.922). CONCLUSION: Delayed phase imaging is useful
      for detecting small HCCs and should be included in dynamic CT examinations of
      patients with liver cirrhosis.

PMID- 17179358
TI  - Transient hepatic intensity differences: part 1, Those associated with focal
      lesions.
AB  - OBJECTIVE: The purpose of our study was to evaluate, on MRI, transient hepatic
      signal intensity differences (THID) that have already been seen on CT as
      transient hepatic attenuation differences (THAD) and to show the range of
      appearance of such arterial phenomena, when associated with focal lesions, in an
      effort to correlate morphology, cause, and pathogenesis. CONCLUSION: Hepatic
      arterial phenomena visualized on MRI should be known and recognized to avoid
      incorrect diagnoses and to improve the characterization of focal liver lesions
      because their shape can lead to an understanding of pathogenetic mechanisms.

PMID- 17179359
TI  - Transient hepatic intensity differences: part 2, Those not associated with focal
      lesions.
AB  - OBJECTIVE: The purpose of our study was to evaluate and to show the range of
      appearance of transient hepatic signal intensity differences when not associated
      with focal lesions, and to correlate morphology, cause, and pathogenesis.
      CONCLUSION: Hepatic arterial phenomena, visualized on MRI and CT, must be
      considered important signs of underlying liver disorders, which these phenomena
      contribute to evaluate. Accordingly, the hepatic arterial phase must always be
      performed on MRI as well as on CT, even if no focal lesion is expected.

PMID- 17179360
TI  - Endoluminal therapy in patients with peripheral arterial disease: prospective
      assessment of quality of life in 190 patients.
AB  - OBJECTIVE: The objective of our study was to assess the impact of endoluminal
      treatment on health-related quality of life in patients with peripheral arterial
      disease. SUBJECTS AND METHODS: Changes in quality of life were prospectively
      evaluated in 190 patients before and 1, 3, 6, and 12 months after treatment.
      Physical, emotional, and general health components were determined using the
      short-form (36 items) health survey (SF-36). Claudicant patients were compared
      with patients who had critical limb ischemia. The influence of the lesion
      location (iliac, femoropopliteal, or crural) restenosis, and additional
      interventions on quality of life were evaluated. RESULTS: Six- and 12-month
      follow-up data were available for 136 and 103 patients, respectively. Significant
      improvements in quality of life were observed in most of the patients after the
      intervention. Many of the SF-36 scores decreased from the 6- to the 12-month
      follow-up but remained significantly higher than the score before the
      intervention. Reduction of bodily pain was the most evident effect of treatment.
      Claudicant patients seemed to benefit more from treatment than patients with
      critical limb ischemia. In terms of SF-36 scores, percutaneous transluminal
      angioplasty of the crural arteries was equally as effective as endoluminal
      revascularization of the iliac and femoropopliteal arteries and multilevel
      interventions were as effective as single-level interventions. The occurrence of
      a restenosis was significantly related to lower SF-36 scores, and restenosis not
      followed by a second intervention was associated with lower SF-36 scores.
      CONCLUSION: Although there were several differences between the groups,
      significant improvements in quality of life up to 12 months after endoluminal
      therapy were observed in most patients.

PMID- 17179361
TI  - Long-term results of uterine artery embolization for symptomatic adenomyosis.
AB  - OBJECTIVE: Controversy exists regarding the effectiveness of uterine artery
      embolization (UAE) in the management of symptomatic adenomyosis. The aim our
      study was to determine the long-term clinical efficacy of UAE in the management
      of symptomatic adenomyosis without fibroids. MATERIALS AND METHODS: The cases of
      all patients who underwent UAE for adenomyosis without fibroids between 1998 and
      2000 were analyzed. This study was a retrospective review of a prospectively
      collected database. Of the 66 patients, 54 patients with a follow-up period of 3
      years or longer were enrolled in the study. Twelve patients were lost to follow
      up. The patients' ages ranged from 29 to 49 years (mean, 40.2 years). The mean
      follow-up period was 4.9 years (range, 3.5-5.8 years). The primary embolic agent
      was polyvinyl alcohol particles (250-710 microm). All patients underwent MRI
      before UAE. Long-term follow-up MRI was performed on 29 patients; 22 of these
      patients had undergone short-term (3.5 months) follow-up MRI. Uterine volume was
      calculated with MR images. Symptom status in terms of menorrhagia and
      dysmenorrhea was scored on a scale of 0-10, 0 being no symptoms and 10 being the
      baseline, or initial symptoms. RESULTS: Thirty-one (57.4%) of the 54 women who
      underwent follow-up had long-term success. Four had immediate treatment failure,
      and 19 had relapses. Changes in mean menorrhagia and dysmenorrhea scores at long
      term follow-up were -5.3 and -5.1, respectively (p < 0.001), representing
      significant relief of symptoms. The time between UAE and recurrence of symptoms
      ranged from 4 to 48 months (mean, 17.3 months). Five patients underwent
      hysterectomy because of symptom recurrence. Mean reduction in volume of the
      uterus was 26.3% at short-term follow-up and 27.4% at long-term follow-up.
      CONCLUSION: We found that UAE is effective in the management of symptomatic
      adenomyosis and has an acceptable long-term success rate. UAE should be
      considered a primary treatment method for patients with symptomatic adenomyosis.
      However, all patients should be given an explanation of the possibility of
      treatment failure, recurrence, and the need for hysterectomy.

PMID- 17179362
TI  - CT-guided percutaneous steroid injection for management of inflammatory
      arthropathy of the temporomandibular joint in children.
AB  - OBJECTIVE: The purposes of this study were to retrospectively review an injection
      technique, to develop a grading system for evaluation of imaging findings, and to
      report preliminary outcome related to percutaneous CT-guided steroid injection
      into the temporomandibular joints of children with inflammatory arthropathy.
      CONCLUSION: CT-guided steroid injection into the temporomandibular joint of
      children with inflammatory arthropathy results in clinical and imaging
      improvement in a substantial proportion of children treated.

PMID- 17179363
TI  - Peripheral tear of the triangular fibrocartilage: depiction with MR arthrography
      of the distal radioulnar joint.
AB  - OBJECTIVE: Although central tears of the triangular fibrocartilage are easily
      seen on imaging, peripheral tears of the ulnar attachment are frequently missed.
      The aim of this study was to evaluate the accuracy of MR arthrography of the
      distal radioulnar joint in depiction of peripheral tears of the triangular
      fibrocartilage. MATERIALS AND METHODS: Forty-one patients (18 women, 23 men; mean
      age, 38 years; age range, 18-60 years) underwent MR arthrography and wrist
      arthroscopy. For MR arthrography, iopamidol (300 mg I/mL) and gadopentetate
      dimeglumine (4 mmol/L) were injected into the distal radioulnar joint. Consensus
      review of both MR arthrograms and conventional arthrograms was performed by two
      experienced musculoskeletal radiologists. Presence or absence of communicating
      and noncommunicating tears of the ulnar attachment of the triangular
      fibrocartilage was recorded. Arthroscopy was used as the standard of reference
      for determining sensitivity, specificity, and accuracy in detection of tears of
      the ulnar attachment. RESULTS: At MR arthrography, communicating tear of the
      ulnar attachment was diagnosed in three patients, noncommunicating tear in 19
      patients, and normal attachment in 19 patients. Arthroscopy revealed peripheral
      tear of the triangular fibrocartilage in all three patients with communicating
      tear, in 14 of 19 patients with noncommunicating tear, and in three of 19
      patients with normal attachment. The sensitivity was 85% (17/20), specificity was
      76% (16/21), and accuracy was 80% (33/41). CONCLUSION: MR arthrography of the
      distal radioulnar joint is accurate in depiction of peripheral tears of the ulnar
      attachment of the triangular fibrocartilage. These tears often appear as
      noncommunicating tears extending from the distal radioulnar joint into the
      triangular fibrocartilage.

PMID- 17179364
TI  - Increased risk of posterior glenoid labrum tears in football players.
AB  - OBJECTIVE: This study was designed to test our hypothesis that football players
      with shoulder pain, shoulder instability, or both requiring MR arthrography for
      evaluation are at an increased likelihood relative to non-football players for
      having a tear of the posterior glenoid labrum. CONCLUSION: We conclude that
      posterior glenoid labrum tears are more prevalent in football players than in non
      football players.

PMID- 17179365
TI  - Extensor retinaculum of the wrist: sonographic characterization and
      pseudotenosynovitis appearance.
AB  - OBJECTIVE: We have found in our practice that the normal extensor retinaculum of
      the wrist may appear hypoechoic on sonography and, because it is closely applied
      to the extensor tendons, may simulate tenosynovitis. This study prospectively
      evaluates the extensor retinaculum in 50 healthy adult volunteers, characterizing
      its sonographic appearance. CONCLUSION: The extensor retinaculum has a
      characteristic appearance on sonography. A hypoechoic appearance from anisotropy
      should not be confused with tenosynovitis.

PMID- 17179367
TI  - Reproducibility of postprocessing of quantitative CT perfusion maps.
AB  - OBJECTIVE: The purpose of this study was to assess interobserver and
      intraobserver variability in evaluation of the reproducibility of quantitative
      data obtained in semiautomated postprocessing of CT perfusion data sets by
      observers of different levels of skill and experience and in fully automated
      postprocessing. MATERIALS AND METHODS: Twenty CT perfusion data sets were
      postprocessed by a neuroradiologist using an automated postprocessing program and
      by five observers (neuroradiology attending, neurology attending, radiology
      resident, senior and junior CT technologists) who received a brief training
      session in use of software for semiautomated postprocessing. For assessment of
      intraobserver variability, each observer repeated postprocessing of 10 CT
      perfusion data sets. Standard regions of interest were placed on identical
      locations for each observer's cerebral blood flow (CBF), cerebral blood volume
      (CBV), and mean transit time (MTT) maps of three brain regions: an ischemia
      infarct region, normal cortical gray matter, and white matter. RESULTS: The
      variability in mean quantitative values of CBF, CBV, and MTT was 2.5-9.5% among
      all observers. Greater variability (20.4%) was introduced with the automated
      program. High correlation was found among all possible pairings of observers (r =
      0.87-0.99). Low correlation was observed between automated postprocessing and
      postprocessing by all observers. Intraobserver variability in quantitative CT
      perfusion data ranged from 0.29% to 10.8%. High intraobserver correlation (r =
      0.91-0.99) was found for the observers. CONCLUSION: Quantitative CBF, CBV, and
      MTT data obtained from postprocessing of CT perfusion data sets are reproducible
      among observers with varying levels of skill and experience. Observer interaction
      with the software is an important component for correct identification of user
      defined parameters. Establishing a uniform and standard postprocessing technique
      is essential for maintaining good reproducibility.

PMID- 17179366
TI  - Cerebral blood volume measurements and proton MR spectroscopy in grading of
      oligodendroglial tumors.
AB  - OBJECTIVE: The purpose of this study was to determine whether perfusion-weighted
      imaging (PWI) and proton MR spectroscopy (MRS) are useful in differentiating high
      and low-grade oligodendroglial tumors. MATERIALS AND METHODS: PWI and MRS
      studies of 22 patients with histologically proven oligodendroglioma or
      oligoastrocytoma (13 low-grade and nine anaplastic tumors) were retrospectively
      reviewed. PWI of 14 subjects was performed with a dynamic contrast-enhanced
      susceptibility-weighted echo-planar technique. Intratumoral relative cerebral
      blood volume ratio was calculated and normalized to the same value in
      contralateral normal-appearing white matter. Multivoxel MRS was performed with a
      point-resolved spectroscopy sequence at a TE of 135 milliseconds in 20 patients
      and with the addition of a TE of 30 seconds in 17 patients. MRS data were
      expressed as intratumoral metabolite ratios (choline to creatine [Cho/Cr],
      choline to N-acetyl aspartate, N-acetyl aspartate to creatine, and myoinositol to
      creatine). RESULTS: Relative cerebral blood volume ratios were significantly
      different (p = 0.004) between low-grade (1.61 +/- 1.20) and high-grade tumors
      (5.45 +/- 1.96). The optimal relative cerebral blood volume ratio cutoff value in
      identification of anaplastic oligodendroglial tumors was 2.14. Analysis of MRS
      data showed significantly higher Cho/Cr ratios (p = 0.002) in high-grade than in
      low-grade tumors. A Cho/Cr ratio cutoff value of 2.33 had the highest accuracy in
      identification of high-grade tumors. CONCLUSION: Relative cerebral blood volume
      measurement and MRS are helpful in differentiating low-grade from anaplastic
      oligodendroglial tumors.

PMID- 17179368
TI  - Atypical imaging findings in a near-fatal case of posterior reversible
      encephalopathy syndrome in a child.

PMID- 17179369
TI  - Sonographically guided core biopsy of a parotid mass.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of
      sonographically guided core biopsy in the evaluation of parotid masses. SUBJECTS
      AND METHODS: Between 1998 and 2004, 135 patients consecutively presenting with a
      parotid mass were prospectively enrolled into this study. A single operator
      performed initial diagnostic sonography and then sonographically guided core
      biopsy using local anesthesia. Biopsy was performed with an 18- or 20-gauge
      needle and a spring-loaded biopsy gun with a mean of two passes per patient.
      Outcome measures were accuracy, sensitivity, specificity, and predictive values
      of sonographically guided core biopsy compared with the final pathologic
      diagnosis in the surgical group. In the nonsurgical group, final diagnosis was
      established on the basis of histologic findings after adequate core biopsy and
      clinical follow-up. RESULTS: All sonographically guided core biopsy specimens
      were considered satisfactory for histologic evaluation. Overall there were 71
      benign tumors, 35 malignant tumors, and 29 miscellaneous, nonneoplastic lesions.
      In 76 (56%) of the 135 patients who underwent surgery, sonographically guided
      core biopsy and surgical histologic findings were correlated for 74 patients. In
      two cases sonographically guided core biopsy and surgical histologic findings did
      not correlate. In one case, the sonographically guided core biopsy finding was
      mucoepidermoid carcinoma, but the final diagnosis was squamous cell carcinoma. In
      the other case, the finding at sonographically guided core biopsy was squamous
      cell carcinoma, but the final diagnosis was mucoepidermoid carcinoma. The
      treatment of these patients was not affected. Fifty-nine (44%) of the 135
      patients avoided surgery. In differentiation of benign from malignant disease,
      sonographically guided core biopsy had a sensitivity, specificity, and diagnostic
      accuracy of 100%. Sonographically guided core biopsy also had positive and
      negative predictive values of 100% in the diagnosis of malignancy. There were no
      significant complications of sonographically guided core biopsy. CONCLUSION:
      Sonographically guided core biopsy is a highly accurate technique for evaluation
      of parotid lesions and can be safely performed as an outpatient procedure.
      Sonographically guided core biopsy has potential advantages over fine-needle
      aspiration cytologic examination, particularly in the typing and grading of
      lymphoma and carcinoma and in improved differentiation of reactive nodal
      hyperplasia from lymphoma. The use of sonographically guided core biopsy may help
      reduce the need for surgical biopsy and facilitates prompt referral to the
      appropriate clinical team.

PMID- 17179370
TI  - Balanced turbo field-echo sequence for MRI of parotid gland diseases.
AB  - OBJECTIVE: A balanced turbo field-echo (FE) sequence is a balanced steady-state
      free precession sequence used for achieving rapid and high imaging. We tested
      whether this imaging technique is applicable to the diagnosis of parotid gland
      diseases. CONCLUSION: The balanced turbo FE sequence is a novel alternative MRI
      technique for the diagnosis of various parotid gland diseases.

PMID- 17179371
TI  - Clinical versus research approach to breast cancer detection with CAD: where are
      we now?

PMID- 17179372
TI  - Performance parameters for screening and diagnostic mammography in a community
      practice: are there differences between specialists and general radiologists?
AB  - OBJECTIVE: The purpose of this study was to compare the performance of general
      radiologists in interpretation of mammograms with that of breast imaging
      specialists in a high-volume community hospital-based private practice. MATERIALS
      AND METHODS: A retrospective observational study was conducted with data
      prospectively collected over a 5-year period in a community hospital-based
      practice in which 106,405 screening and 52,149 diagnostic mammograms were
      performed. The performance of three radiologists specializing in breast imaging
      was compared with that of six general radiologists. The following data were
      extracted and analyzed: recall rate, biopsy recommendation rate, and cancer
      detection rate. Statistical analysis was performed with a chi-square test and two
      tailed calculation of p values. RESULTS: The recall rates of the specialists and
      generalists were nearly the same at 6.5% and 6.7%, respectively. The biopsy
      recommendation rate at recall from screening examinations was nearly the same for
      generalists and specialists (1.2% and 1.1%, respectively; p = 0.4504). This rate
      also was similar for diagnostic examinations (8.5% for generalists; 8.4% for
      specialists; p = 0.4086). The cancer detection rate in the screening setting was
      slightly higher for specialists than for generalists: 2.5 and 2.0 cancers per
      1,000 cases, respectively (p = 0.0614). The cancer detection rate in the
      diagnostic setting was 24.2% higher among specialists (20.0 cancers per 1,000
      cases) compared with generalists (16.1 cancers per 1,000 cases) (p = 0.0177).
      CONCLUSION: The only statistically significant difference between generalists and
      specialists was in cancer detection rate among patients undergoing diagnostic
      mammography. No statistically significant difference was identified between the
      two groups in terms of recall rate, biopsy recommendation rate, or percentage of
      favorable-prognosis cases of cancer detected. There was a trend toward greater
      cancer detection by specialists in the screening setting.

PMID- 17179373
TI  - Trends in time to completion of mammographic screening and follow-up services.
AB  - OBJECTIVE: The popular press has raised questions about mammographic capacity in
      the United States, but mammographic utilization data have not been used to inform
      these concerns. We used data for the period 1995-2002 from the New Mexico
      Mammography Project to assess trends in time to completion of mammographic
      screening and follow-up services. CONCLUSION: The median time to return
      mammographic screening changed little over time, but trends in the time required
      to complete recommended follow-up services varied by type of service and urban or
      rural residence. Further monitoring of time required to complete screening and
      follow-up services in other regions can inform debates on mammographic capacity.

PMID- 17179374
TI  - Uterine smooth-muscle tumors with unusual growth patterns: imaging with
      pathologic correlation.
AB  - OBJECTIVE: This essay illustrates the salient features of variant smooth-muscle
      tumors on multiple imaging techniques with correlative pathology. We describe how
      recognition of these features allows the radiologist to distinguish a uterine
      leiomyoma variant from the classic fibroid or a leiomyosarcoma. Finally, we
      highlight the role of the radiologist in triaging these patients to surgical
      versus medical management and in surgical planning. CONCLUSION: Parasitic
      leiomyoma, intravenous leiomyomatosis, disseminated peritoneal leiomyomatosis,
      and benign metastasizing leiomyoma show key features on multiple imaging
      techniques that correlate with pathology findings. In the appropriate clinical
      setting, the radiologist should include these unusual lesions in the broader
      differential diagnosis of smooth-muscle tumors and, in certain cases, aid in
      surgical planning.

PMID- 17179375
TI  - Clinical value of manual fusion of PET and CT images in patients with suspected
      recurrent colorectal cancer.
AB  - OBJECTIVE: The purpose of this study was to compare the diagnostic performance of
      manually fused PET images obtained using 18F-FDG and CT images with that of CT
      alone, PET alone, and conventional side-by-side review of PET images and CT
      images (hereafter referred to as "PET + CT") in patients with suspected recurrent
      colorectal cancer. MATERIALS AND METHODS: Ethics committee approval and informed
      consent were obtained. Sixty-three patients with suspected recurrent colorectal
      cancer underwent whole-body 18F-FDG PET followed by diagnostic CT. The acquired
      PET and CT images were merged on a workstation on a pixel-to-pixel basis. CT,
      PET, PET + CT, and fused images were evaluated separately in terms of the
      presence or absence of recurrence, new metastases, or both using a 5-point
      grading scale (0 = definitely negative, 1 = probably negative, 2 = equivocal, 3 =
      probably positive, and 4 = definitely positive). Lesions determined to be grade 3
      or 4 were considered positive, and diagnostic accuracy and certainty were
      evaluated with statistical analysis using the chi-square test for independence.
      RESULTS: Of 119 pathologically or clinically confirmed lesions in 36 patients,
      evaluation of CT, PET, PET + CT, and fused images resulted in the detection of 75
      (63%), 84 (71%), 91 (76%), and 111 (93%) lesions, respectively (p < 0.01) with
      the number of grade 4 lesions detected being 59 (50%), 72 (61%), 84 (71%), and
      108 (91%), respectively (p < 0.01). Overall, the diagnostic accuracy of CT, PET,
      PET + CT, and fused images according to patient were 78%, 79%, 84%, and 92%,
      respectively (p = 0.13). CONCLUSION: Interpreting fused images provided more
      accurate diagnoses than interpreting CT, PET, or PET + CT images. This method of
      manually fusing separately obtained PET and CT images increased the diagnostic
      certainty for detecting colorectal cancer recurrence and decreased the number of
      equivocal cases.

PMID- 17179376
TI  - Preoperative MR angiography in free fibula flap transfer for head and neck
      cancer: clinical application and influence on surgical decision making.
AB  - OBJECTIVE: We review the fibular free flap surgical procedure to illustrate the
      usefulness of preoperative lower limb MR angiography and to show how calf
      vascular anatomy on MR angiography affects patient surgical management.
      CONCLUSION: With its high positive predictive value and sensitivity, preoperative
      MR angiography can improve the chances of a successful outcome at the recipient
      mandibular site. It provides the reconstructive surgeon with a road map,
      revealing vascular anomalies or disease that could alter or contraindicate
      surgery.

PMID- 17179377
TI  - Sonography of pediatric small-bowel intussusception: differentiating surgical
      from nonsurgical cases.
AB  - OBJECTIVE: The purpose of this study was to determine whether there are clinical
      or sonographic findings that can be used to differentiate benign self-limited
      small-bowel intussusception from pathologic small-bowel intussusception that
      necessitates surgical intervention. MATERIALS AND METHODS: A retrospective search
      was performed of abdominal sonograms obtained at two institutions between January
      1996 and June 2005. Sonographic findings were correlated with medical and
      surgical records. RESULTS: A total of 35 cases of isolated small-bowel
      intussusception were found. Thirteen (37%) of these cases necessitated surgical
      intervention, and 22 (63%) of the cases were benign and self-limiting. Patients
      with self-limiting intussusception were younger than patients with
      intussusception necessitating surgical intervention (mean, 4.2 vs 7.5 years; p =
      0.0327). Abdominal sonograms depicted ascites and small-bowel obstruction
      significantly more frequently in patients with small-bowel intussusception
      necessitating surgery (n = 7 [54%] for each finding) than in patients with self
      limiting intussusception (n = 2 [9%], n = 0) (p = 0.006 and p = 0.0003,
      respectively). At sonography, patients who later underwent surgical intervention
      had small-bowel intussusception of significantly greater length (mean, 7.3 cm)
      than those treated conservatively (mean length, 1.9 cm) (p < 0.0001).
      Intussusception length greater than 3.5 cm was considered a sensitive and
      specific independent predictor of the need for surgery (sensitivity, 93%;
      specificity, 100%). CONCLUSION: When small-bowel intussusception is detected in
      infants and children undergoing abdominal sonography, intussusception length
      greater than 3.5 cm is a strong independent predictor of the need for surgical
      intervention.

PMID- 17179379
TI  - Maternal provisioning in Ophionereis fasciata and O. schayeri: brittle stars with
      contrasting modes of development.
AB  - Evolutionary change from planktotrophic to lecithotrophic development in
      echinoderms is closely tied to an increase in maternal provisioning. We provide
      the first data on the major energetic constituents in the eggs of two ophiuroids,
      the planktotroph Ophionereis fasciata (egg diameter 103 microm) and the
      lecithotroph O. schayeri (egg diameter 248 microm), to document changes in
      maternal investment associated with the switch to lecithotrophy in O. schayeri.
      Lipid classes in the eggs of the two species did not differ except for the
      presence of small amounts of wax esters in the eggs of O. schayeri. Production of
      a large egg in O. schayeri is mostly due to enhanced deposition of one energy
      storage lipid, triglyceride. The eggs of O. schayeri are not simply scaled-up
      versions of the ancestral-type eggs of O. fasciata. The relationship between
      lipid and protein content and egg volume conformed to the relationship previously
      established for echinoderm eggs. Surprisingly, total lipid and protein data for
      the eggs of O. schayeri grouped with data for the eggs of planktotrophic
      echinoderms. The eggs of O. schayeri are small compared with those of other
      echinoderms with lecithotrophic development, and their energetic contents may
      approach the minimum provisions necessary to permit development without feeding.

PMID- 17179380
TI  - Induction of metamorphosis decreases nitric oxide synthase gene expression in
      larvae of the marine mollusc Ilyanassa obsoleta (say).
AB  - Many marine organisms spend the early part of their lives as larvae suspended in
      the water column before metamorphosing into benthic reproductive adults.
      Metamorphosis does not occur until a larva has become competent to respond to
      appropriate stimuli and after a suitable habitat for the young juvenile has been
      encountered. The gaseous neurotransmitter nitric oxide is thought to be important
      in the regulation of metamorphosis by holding the organism in the larval state.
      We have investigated expression of the neuronal nitric oxide synthase (nNOS) gene
      in larval and metamorphosing individuals of the marine mud snail Ilyanassa
      obsoleta. Our results indicate that nNOS is expressed at constant levels
      throughout larval development. In contrast, expression of nNOS decreases markedly
      during the first 24 h of metamorphosis. Our observations support previous
      findings that demonstrate that nitric oxide is present in larvae though
      competence. The decrease in nNOS gene expression that occurs during metamorphosis
      corresponds with a previously described reduction in nNOS activity.

PMID- 17179381
TI  - Patterns of motor activity in the isolated nerve cord of the octopus arm.
AB  - The extremely flexible octopus arm provides a unique opportunity for studying
      movement control in a highly redundant motor system. We describe a novel
      preparation that allows analysis of the peripheral nervous system of the octopus
      arm and its interaction with the muscular and mechanosensory elements of the
      arm's intrinsic muscular system. First we examined the synaptic responses in
      muscle fibers to identify the motor pathways from the axial nerve cord of the arm
      to the surrounding musculature. We show that the motor axons project to the
      muscles via nerve roots originating laterally from the arm nerve cord. The motor
      field of each nerve is limited to the region where the nerve enters the arm
      musculature. The same roots also carry afferent mechanosensory information from
      the intrinsic muscle to the axial nerve cord. Next, we characterized the pattern
      of activity generated in the dorsal roots by electrically stimulating the axial
      nerve cord. The evoked activity, although far reaching and long lasting, cannot
      alone account for the arm extension movements generated by similar electrical
      stimulation. The mismatch between patterns of activity in the isolated cord and
      in an intact arm may stem from the involvement of mechanosensory feedback in
      natural arm extension.

PMID- 17179382
TI  - Loss of escape-related giant neurons in a spiny lobster, Panulirus argus.
AB  - When attacked, many decapod crustaceans perform tailflips, which are triggered by
      a neural circuit that includes lateral giant interneurons, medial giant
      interneurons, and fast flexor motor giant neurons (MoGs). Slipper lobsters
      (Scyllaridae) lack these giant neurons, and it has been hypothesized that
      behavioral (e.g., digging) and morphological (e.g., flattening and armor)
      specializations in this group caused the loss of escape-related giant neurons. To
      test this hypothesis, we examined a species of spiny lobster, Panulirus argus.
      Spiny lobsters belong to the sister taxon of the scyllarids, but they have a more
      crayfish-like morphology than scyllarids and were predicted to have escape
      related giant neurons. Ventral nerve cords of P. argus were examined using
      paraffin-embedded sections and cobalt backfills. We found no escape-related giant
      neurons and no large axon profiles in the dorsal region of the nerve cord of P.
      argus. Cobalt backfills showed one fewer fast flexor motor neuron than in species
      with MoGs and none of the fast flexor motor neurons show any of the anatomical
      specializations of MoGs. This suggests that all palinuran species lack this giant
      escape circuit, and that the loss of rapid escape behavior preceded, and may have
      driven, alternative predator avoidance and anti-predator strategies in
      palinurans.

PMID- 17179383
TI  - Development of embryonic and larval cells containing serotonin, catecholamines,
      and FMRFamide-related peptides in the gastropod mollusc Phestilla sibogae.
AB  - The present immunocytochemical study provides one of the first detailed
      descriptions of the development of cells containing a variety of
      neurotransmitters during much of the larval life of a nudibranch gastropod.
      Throughout much of early development, serotonergic cells were located only in the
      apical organ; as larvae approached metamorphosis, serotonergic cells were also
      detected in the cerebropleural and pedal ganglia. Cells exhibiting tyrosine
      hydroxylase immunoreactivity (indicative of catecholamine synthesis) were first
      located near the mouth but by late embryonic stages were also located in the
      apical organ and near the velum and eyes. By late larval stages, numerous
      catecholaminergic cells were found in the foot, with concentrations in the
      propodium. Finally, the first cells exhibiting FMRFamide immunoreactivity were
      detected posterior to the neuropil of the cerebropleural ganglia in the early
      embryo. Fibers that presumably originated from these cells subsequently invaded
      the cerebral and pedal ganglia and the apical organ. By early larval stages, a
      second pair of peptidergic neurons was located near the first pair, and
      additional peptidergic neurons were located in the apical organ and peripheral
      positions in the foot and medial and dorsal to the eyes. In addition to providing
      a unique phyletic perspective to our understanding of gastropod neural
      development, the present study also sets the stage for future studies into
      changes in the nervous system as this gastropod undergoes metamorphosis.

PMID- 17179384
TI  - Color polymorphism and genetic structure in the sea star Pisaster ochraceus.
AB  - The sea star Pisaster ochraceus is one of the more striking species on the rocky
      shores of the Northeast Pacific, in part due to the dramatic color polymorphism
      of the adults. Along the open Pacific coast, Pisaster populations are 6%-28%
      orange, with a small percentage of brilliant purple stars and a large percentage
      of reddish-brown to dull purple ones. However, populations in the San Juan Island
      Archipelago (Washington, USA) and the southern Strait of Georgia (British
      Columbia, Canada) are almost entirely brilliant purple. The factors that maintain
      the color polymorphism, and those that contribute to among-site variation in
      color frequencies, remain unknown. We examined the relationships between color
      frequencies and several ecological and morphological variables, and conducted a
      large-scale phylogeographic survey of Pisaster populations. We found very low
      population genetic structure, suggesting that gene flow is high and geographic
      variation in color frequencies is not a vestige of Pleistocene glacial refugia.
      Color frequencies are also unrelated to adult size and to the frequency of injury
      within a population. However, there are suggestive relationships between color
      frequency and diet, and with areas of potentially low salinity. We propose that,
      although the color polymorphism may have an underlying genetic component, the
      regional-scale variation in color frequency is ecologically controlled.

PMID- 17179385
TI  - Interspecific comparison of the mechanical properties of mussel byssus.
AB  - Byssally tethered mussels are found in a variety of habitats, including rocky
      intertidal, salt marsh, subtidal, and hydrothermal vents. One key to the survival
      of mussels in these communities is a secure attachment, achieved by the
      production of byssal threads. Although many studies have detailed the unique
      biomechanical properties of byssal threads, only a few prevalent species have
      been examined. This study assesses the variation in the mechanical properties of
      byssus in a broad range of mussel species from diverse environments, including
      intertidal and subtidal Mytilus edulis, Modiolus modiolus, Geukensia demissa,
      Bathymodiolus thermophilus, and Dreissena polymorpha. A tensometer was used to
      measure quasi-static and dynamic mechanical properties of individual threads, and
      several aspects of morphology were quantified. The results indicate that thread
      mechanical properties vary among mussel species, and several novel properties
      were observed. For example, of the species examined, D. polymorpha threads were
      the strongest, stiffest, least resilient, and fastest to recover after partial
      deformation. Threads of M. modiolus were characterized by the presence of two
      distinct yield regions prior to tensile failure. This comparative study not only
      provides insight into the ecological limitations and evolution of mussels, but
      also suggests new models for the design of novel biomimetic polymers.

PMID- 17179386
TI  - Peritrophic membrane of the penaeid shrimp Sicyonia ingentis: structure,
      formation, and permeability.
AB  - Peritrophic membranes (PTMs) are secreted acellular layers that separate ingested
      materials from the gut epithelium in a variety of invertebrates. In insects and
      crustaceans, PTMs are produced in the midgut trunk (MGT, or intestine), but the
      MGT in decapod crustaceans, unlike that of insects, is not involved with
      digestion or absorption of food. We demonstrate that the PTM in the penaeid
      shrimp Sicyonia ingentis is similar to that in other crustaceans that have been
      studied and is primarily composed of chitin. The lectin WGA binds only to the PTM
      and glycocalyx along the microvilli of the midgut cells, which is consistent with
      the suggestion that the chitin is synthesized along the microvilli. The PTM is
      only permeable to inert particles smaller than 20 nm. We also describe the
      secretion of granules, which fill the apices of the epithelial cells, into the
      ectoperitrophic space. Although their function is not clear, they do not
      contribute to the PTM.

PMID- 17179387
TI  - Stocking density at early developmental stages affects growth and sex ratio in
      the European eel (Anguilla anguilla).
AB  - To investigate the effect of stocking density on growth and sex ratio in European
      eel, four constant density conditions were tested during the transition from the
      glass to the elver stage for 90 days (Period 1). The test conditions combined the
      weight of fish per unit surface or volume (surface density or volume density)
      resulting in four experimental groups: low surface density (0.5 kg/m(2)) and low
      volume density (5 kg/m(3)) (group S(0.5)V(5)); low surface density (0.5 kg/m(2))
      and high volume density (10 kg/m(3)) (group S(0.5)V(10)); high surface density (2
      kg/m(2)) and low volume density (5 kg/m(3)) (group S(2)V(5)); and high surface
      density (2 kg/m(2)) and high volume density (10 Kg/m(3)) (group S(2)V(10)).
      Subsequently, fish from the S(0.5)V(5), S(2)V(5), and S(2)V(10) groups were
      transferred to low density conditions (0.1-0.4 kg/m(2) or 0.1-0.3 kg/m(3)) for
      another 21 months (630 days; Period 2). After Period 1, fish maintained at high
      surface density, regardless of the volume density, showed higher standard growth
      rates (SGRs) and RNA/DNA ratio in muscle than those cultured at low surface
      density. The percentage of mortality was similar in three of the groups (34.2%
      41.8%), but not in the S(2)V(10) group (83.3%). At the end of Period 2, most fish
      (about 95%) exhibited fully differentiated gonads, but different sex ratios were
      observed in each group. Thus, the S(2)V(5) group showed a higher proportion of
      females (36.1%) and a lower proportion of males (56.8%) than the S(0.5)V(5) group
      (11.4% and 72.5%, respectively), while all survivor fish from the S(2)V(10) group
      developed into females. The gonadosomatic index and SGR were higher in females
      than in males. These results suggest that glass eels maintained at high surface
      density during the first months of growth tend to develop into females. The data
      also indicate that growth and sex ratio are linked processes during eel
      development, with growth seeming to be sex dependant rather than being influenced
      by the density conditions in which glass eels are maintained.

PMID- 17179389
TI  - Prior exercise increases phosphorylation of Akt substrate of 160 kDa (AS160) in
      rat skeletal muscle.
AB  - The main purpose of this study was to determine whether the increased glucose
      transport (GT) found immediately postexercise (IPEX) or 4 h postexercise (4hPEX)
      is accompanied by increased phosphorylation of Akt substrate of 160 kDa (AS160, a
      protein regulator of GLUT4 translocation). Paired epitrochlearis muscles were
      dissected from rats (sedentary or IPEX, 2-h swim) and used to measure protein
      phosphorylation and insulin-independent GT. IPEX values exceeded sedentary values
      for GT and phosphorylations of AS160, AMP-activated protein kinase (pAMPK) and
      acetyl-CoA carboxylase (pACC) but not for AS160 abundance or phosphorylation of
      Akt serine (pSerAkt), Akt threonine (pThrAkt), or glycogen synthase kinase-3
      (pGSK3). AS160 phosphorylation was significantly correlated with GT (R=0.801,
      P<0.01) and pAMPK (R=0.655, P<0.05). Muscles from other rats were studied 4hPEX
      along with sedentary controls. One muscle per rat was incubated without insulin,
      and the contralateral muscle was incubated with insulin. 4hPEX values exceeded
      sedentary values for insulin-stimulated GT. The elevated pAMPK and pACC found
      IPEX had reversed by 4hPEX. Insulin caused a significant increase in pSerAkt,
      pThrAkt, pGSK3, and AS160 phosphorylation with or without exercise. Exercise
      significantly increased AS160 phosphorylation, regardless of insulin, with
      unchanged AS160 abundance. Among the signaling proteins studied, insulin
      stimulated GT was significantly correlated only with insulin-stimulated pThrAkt
      (R=0.720, P<0.0005). The results are consistent with a role for increased AS160
      phosphorylation in the increased insulin-independent GT IPEX, and the exercise
      effects on AS160 phosphorylation and/or pThrAkt at 4hPEX are potentially relevant
      to the increased insulin-stimulated glucose transport at this time.

PMID- 17179390
TI  - Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo
      increases fatty acid oxidation and reduces triacylglycerol esterification.
AB  - A key regulatory point in the control of fatty acid (FA) oxidation is thought to
      be transport of FAs across the mitochondrial membrane by carnitine
      palmitoyltransferase I (CPT I). To investigate the role of CPT I in FA
      metabolism, we used in vivo electrotransfer (IVE) to locally overexpress CPT I in
      muscle of rodents. A vector expressing the human muscle isoform of CPT I was
      electrotransferred into the right lateral muscles of the distal hindlimb
      [tibialis cranialis (TC) and extensor digitorum longus (EDL)] of rats, and a
      control vector expressing GFP was electrotransferred into the left muscles.
      Initial studies showed that CPT I protein expression peaked 7 days after IVE
      (+104%, P<0.01). This was associated with an increase in maximal CPT I activity
      (+30%, P < 0.001) and a similar increase in palmitoyl-CoA oxidation (+24%;
      P<0.001) in isolated mitochondria from the TC. Importantly, oxidation of the
      medium-chain FA octanoyl-CoA and CPT I sensitivity to inhibition by malonyl-CoA
      were not altered by CPT I overexpression. FA oxidation in isolated EDL muscle
      strips was increased with CPT I overexpression (+28%, P<0.01), whereas FA
      incorporation into the muscle triacylglycerol (TAG) pool was reduced (-17%,
      P<0.01). As a result, intramyocellular TAG content was decreased with CPT I
      overexpression in both the TC (-25%, P<0.05) and the EDL (-45%, P<0.05). These
      studies demonstrate that acute overexpression of CPT I in muscle leads to a
      repartitioning of FAs away from esterification and toward oxidation and highlight
      the importance of CPT I in regulating muscle FA metabolism.

PMID- 17179391
TI  - Long-chain n-3 polyunsaturated fatty acids dissociate phosphorylation of Akt from
      phosphatidylinositol 3'-kinase activity in rats.
AB  - We examined whether a low amount of dietary long-chain n-3 polyunsaturated fatty
      acids (LC n-3 PUFA) modulated phosphatidylinositol 3'-kinase (PI 3-kinase)
      activity and downstream Akt phosphorylation differently in normal or insulin
      resistant rats. Rats were fed for 28 days with either a control diet containing
      14.6% of metabolizable energy (ME) as peanut-rape oil (PR) or an n-3 diet where
      4.9% of ME as PR was replaced by fish oil. Over the last 5 days, rats received 9
      per thousand NaCl or dexamethasone (1 mg/kg). Insulin stimulation of both PI 3
      kinase activity and Akt serine(473) phosphorylation and modulation of GLUT4
      content were studied in liver, muscle, and adipose tissue (AT). Glucose tolerance
      and insulin sensitivity were determined by an oral glucose challenge. In muscle
      and AT, LC n-3 PUFA abolished insulin-stimulated PI 3-kinase activity. These
      effects were not paralleled by defects in Akt serine(473) phosphorylation, which
      was even increased in AT. Dexamethasone abolished insulin-stimulated PI 3-kinase
      activity in all tissues, whereas Akt serine(473) phosphorylation was markedly
      reduced in muscle but unaltered in liver and AT. Such tissue-specific
      dissociating effects of LC n-3 PUFA on PI 3-kinase/Akt activation took place
      without alteration of glucose metabolism. Maintenance of a normal glucose
      metabolism by the n-3 diet despite abolition of PI 3-kinase activation was likely
      explained by a compensatory downstream Akt serine(473) phosphorylation. The
      inability of LC n-3 PUFA to prevent insulin resistance by dexamethasone could
      result from the lack of such a dissociation.

PMID- 17179392
TI  - Glucose intolerance and reduced islet blood flow in transgenic mice expressing
      the FRK tyrosine kinase under the control of the rat insulin promoter.
AB  - The FRK tyrosine kinase has previously been shown to transduce beta-cell
      cytotoxic signals in response to cytokines and streptozotocin and to promote beta
      cell proliferation and an increased beta-cell mass. We therefore aimed to further
      evaluate the effects of overexpression of FRK tyrosine kinase in beta-cells. A
      transgenic mouse expressing kinase-active FRK under control of the insulin
      promoter (RIP-FRK) was studied with regard to islet endocrine function and
      vascular morphology. Mild glucose intolerance develops in RIP-FRK male mice of at
      least 4 mo of age. This effect is accompanied by reduced glucose-stimulated
      insulin secretion in vivo and reduced second-phase insulin secretion in response
      to glucose and arginine upon pancreas perfusion. Islets isolated from the FRK
      transgenic mice display a glucose-induced insulin secretory response in vitro
      similar to that of control islets. However, islet blood flow per islet volume is
      decreased in the FRK transgenic mice. These mice also exhibit a reduced islet
      capillary lumen diameter as shown by electron microscopy. Total body weight and
      pancreas weight are not significantly affected, but the beta-cell mass is
      increased. The data suggest that long-term expression of active FRK in beta-cells
      causes an in vivo insulin-secretory defect, which may be the consequence of islet
      vascular abnormalities that yield a decreased islet blood flow.

PMID- 17179393
TI  - Estrogen potentiates adrenocortical responses to stress in female rats.
AB  - It is well established that estrogens markedly enhance the glucocorticoid
      response to acute stress in females. However, the precise mechanism responsible
      for this regulation is poorly understood. Here, we tested whether estrogens
      enhance the activation of the paraventricular nucleus (PVN) of the hypothalamus
      by measuring stress-induced c-fos mRNA expression in the PVN of restraint
      stressed ovariectomized (OVX) rats treated with physiologically relevant doses of
      estradiol (E(2)), the major female estrogen. As expected, E(2) enhanced plasma
      corticosterone responses to restraint in OVX females. However, E(2) markedly
      attenuated the stress-induced c-fos gene expression in the PVN and inhibited
      plasma ACTH responses in these animals. Furthermore, E(2)-inhibitory effects were
      mimicked by progesterone (P) alone or in combination with E(2). Interestingly,
      the suppressive central effects of both E(2) and P were apparently independent of
      basal paraventricular corticotropin-releasing hormone (CRH) transcription, since
      these ovarian steroids did not significantly affect PVN CRH mRNA expression in
      unstressed rats. These unexpected findings suggested that E(2) promotes
      glucocorticoid hypersecretion in females by additional peripheral (i.e., adrenal)
      mechanisms. Indeed, E(2) markedly enhanced plasma corticosterone responses and
      adrenal corticosterone content in dexamethasone-blocked OVX rats challenged with
      varying doses of exogenous ACTH. These results suggest that enhanced adrenal
      sensitive to ACTH is an important physiological mechanism mediating E(2)-related
      glucocorticoid hypersecretion in stressed females.

PMID- 17179394
TI  - Peripheral arteries in diabetic patients: standard bolus-chase and time-resolved
      MR angiography.
AB  - PURPOSE: To prospectively determine the diagnostic performance of a combination
      of standard bolus-chase magnetic resonance (MR) angiography and MR angiography
      with time-resolved imaging of contrast kinetics (TRICKS) for depicting severity
      of peripheral vascular disease of the lower extremity, including the pedal
      arteries, in diabetic patients with digital subtraction angiography (DSA) as the
      reference standard. MATERIALS AND METHODS: An ethical committee approved this
      study; written informed consent was obtained from patients. Standard three
      station and TRICKS MR angiography of the calf and foot were performed in 31
      consecutive diabetic patients (23 men, eight women; mean age, 67 years; range, 43
      81 years). Two readers separately assessed images of arterial segments as
      diagnostic or nondiagnostic and graded stenosis. Results were compared with those
      at DSA when the corresponding arterial segments were considered diagnostic at
      DSA. Wilcoxon signed rank test was used to determine if a significant difference
      between imaging techniques existed, and kappa statistics were used to determine
      interobserver agreement. RESULTS: The difference between standard MR angiography
      and DSA regarding the number of diagnostic segments in the thigh was not
      significant (P = .50). A significantly higher number of calf and foot segments
      was considered diagnostic at TRICKS MR angiography than at standard MR
      angiography (P < .025). Sixteen of 26 segments in the foot that were considered
      nondiagnostic at DSA were considered diagnostic at TRICKS MR angiography. Average
      sensitivity of standard MR angiography for depicting hemodynamically significant
      arterial stenosis was 84% (reader 1) and 83% (reader 2) in the thigh and 78%
      (reader 1) and 80% (reader 2) in the calf. For both readers, average specificity
      was 97% in the thigh and 90% in the calf. Sensitivity and specificity of TRICKS
      MR angiography in the calf and foot were improved compared with those at standard
      MR angiography. CONCLUSION: TRICKS MR angiography of the distal calf and pedal
      vessels is superior to standard MR angiography regarding the number of diagnostic
      segments and assessment of the degree of luminal narrowing.

PMID- 17179395
TI  - Subarachnoid hemorrhage in the subacute stage: elevated apparent diffusion
      coefficient in normal-appearing brain tissue after treatment.
AB  - PURPOSE: To prospectively evaluate whether subarachnoid hemorrhage (SAH) is
      associated with a change in the apparent diffusion coefficient (ADC) in normal
      appearing brain parenchyma. MATERIALS AND METHODS: Institutional review board
      approval and informed consent were obtained for all patient and volunteer
      studies. One hundred patients (48 men, 52 women; mean age, 52 years +/- 12
      [standard deviation]) with aneurysmal SAH underwent conventional and diffusion
      weighted magnetic resonance (MR) imaging at a mean of 9 days +/- 3 after SAH to
      evaluate possible lesions caused by SAH, treatment of SAH, and vasospasm.
      Aneurysms were treated surgically (n = 70) or endovascularly (n = 30) before MR
      imaging. Diffusion-weighted MR imaging was performed at 1-year follow-up in 30
      patients (10 men, 20 women; mean age, 51 years +/- 11). Thirty healthy age
      matched volunteers (11 men, 19 women; mean age, 54 years +/- 16) underwent MR
      imaging with an identical protocol. ADC values were measured bilaterally in the
      gray and white matter (parietal, frontal, temporal, occipital lobes; cerebellum;
      caudate nucleus; lentiform nucleus; thalamus; and pons) that appeared normal on
      T2-weighted and diffusion-weighted MR images. Linear mixed model was used for
      comparison of ADC values of supratentorial gray matter and white matter; general
      linear regression analysis was used for comparison of ADC values of cerebellum
      and pons. RESULTS: In patients with SAH, the ADC values in normal-appearing white
      matter, with a single exception in the frontal lobe (P = .091), were
      significantly higher than they were in healthy volunteers (P </= .011). The
      differences disappeared by 1 year, except in parietal white matter (P = .045).
      The ADC values of cortical gray matter did not significantly differ between
      patients and volunteers (P >/= .121). CONCLUSION: SAH and its treatment may cause
      global mild vasogenic edema in white matter and deep gray matter that is
      undetectable on T2-weighted and diffusion-weighted MR images but is detectable by
      measuring the ADC value in the subacute stage of SAH.

PMID- 17179396
TI  - High-grade prostatic intraepithelial neoplasia in patients with prostate cancer:
      MR and MR spectroscopic imaging features--initial experience.
AB  - PURPOSE: To retrospectively determine the magnetic resonance (MR) and MR
      spectroscopic imaging features of high-grade prostatic intraepithelial neoplasia
      (HGPIN) in patients with prostate cancer. MATERIALS AND METHODS: Approval of the
      committee on human research was obtained, with a waiver of consent for this HIPAA
      compliant study. Endorectal MR imaging and MR spectroscopic imaging were
      performed in 48 men (mean age, 59 years; range, 47-75 years) prior to radical
      prostatectomy for prostate cancer. T2-weighted signal intensity and metabolic
      ratios of peripheral zone HGPIN foci of 6 mm or greater in diameter were recorded
      by two readers with knowledge of step-section histopathologic findings using
      areas of confirmed normal and cancerous peripheral zone tissue for comparison. A
      random effects statistical model was used to compare metabolic ratios from
      normal, HGPIN, and cancer voxels. RESULTS: A total of 123 peripheral zone HGPIN
      foci with a mean diameter of 3 mm (range, 1-28 mm) were identified in 37 (77%)
      patients, but only 20 foci in 14 patients had a diameter of 6 mm or greater. Six
      foci were excluded, yielding 14 large HGPIN lesions from 11 patients in the final
      statistical analysis. The larger HGPIN foci were not associated with any focal
      reduction in T2-weighted signal intensity but demonstrated metabolic findings
      intermediate between normal and cancerous tissue; the mean ratios of choline
      (Cho) to creatine (Cr) for normal, HGPIN, and cancer were 0.92, 1.75, and 1.99,
      respectively, (P < .01), and the corresponding ratios of Cho plus Cr to citrate
      were 0.34, 0.50, and 0.78 (P < .01). CONCLUSION: HGPIN is metabolically
      intermediate between normal peripheral zone tissue and prostate cancer at MR
      spectroscopic imaging but does not manifest any MR imaging abnormality and is
      rarely of sufficient size to cause substantial error in evaluation of peripheral
      zone tumor extent in patients with prostate cancer.

PMID- 17179398
TI  - Assessment of airways with three-dimensional quantitative thin-section CT: in
      vitro and in vivo validation.
AB  - PURPOSE: To prospectively validate the ability of customized three-dimensional
      (3D) software to enable bronchial tree skeletonization, orthogonal reconstruction
      of the main bronchial axis, and measurement of cross-sectional wall area (WA) and
      lumen area (LA) of any visible bronchus on thin-section computed tomographic (CT)
      images. MATERIALS AND METHODS: Institutional review board approval and patient
      agreement and informed consent were obtained. Software was validated in a phantom
      that consisted of seven tubes and an excised human lung obtained and used
      according to institutional guidelines. In vivo validation was performed with
      multi-detector row CT in six healthy subjects (mean age, 47 years; range, 20-55
      years). Intra- and interobserver agreement and reproducibility over time for
      bronchial tree skeletonization were evaluated with Bland-Altman analysis.
      Concordance in identifying bronchial generation was assessed with the kappa
      statistic. WA and LA obtained with the manual method were compared with WA and LA
      obtained with validated software by means of the Wilcoxon test and Bland-Altman
      analysis. RESULTS: WA and LA measurements in the phantom were reproducible over
      multiple sessions (P > .90) and were not significantly different from WA and LA
      assessed with the manual method (P > .62). WA and LA measurements in the excised
      lung and the subjects were not different from measurements obtained with the
      manual method (intraclass correlation coefficient > 0.99). All lobar bronchi and
      80.8% of third generation bronchi, 72.5% of fourth generation bronchi, and 37.7%
      of fifth generation bronchi were identified in vivo. Intra- and interobserver
      agreement and reproducibility over time for airway skeletonization and
      concordance in identifying bronchial generation were good to excellent
      (intraclass correlation coefficient > 0.98, kappa > 0.54, respectively).
      CONCLUSION: This method enables accurate and reproducible measurement of WA and
      LA on reformatted CT sections perpendicular to the main axis of bronchi visible
      on thin-section CT scans.

PMID- 17179397
TI  - Multiple Myeloma: Molecular Imaging with 11C-Methionine PET/CT--Initial
      Experience.
AB  - PURPOSE: To prospectively assess molecular imaging of multiple myeloma (MM) by
      using the radiolabeled amino acid carbon 11 ((11)C) methionine and positron
      emission tomography (PET)/computed tomography (CT). MATERIALS AND METHODS: The
      study was approved by the institutional local ethics committee and the national
      radiation protection authorities. All patients with MM and control patients gave
      written informed consent. Nineteen patients with MM (11 women, eight men; age
      range, 42-64 years) and 10 control patients with hyperparathyroidism without
      hematologic diseases (six women, four men; age range, 43-75 years) underwent
      PET/CT 20 minutes after injection of a mean of 1.0 GBq +/- 0.2 (standard
      deviation) (11)C-methionine. Presence and extent of CT-assessed tumor
      manifestations and (11)C-methionine bone marrow (BM) uptake were determined on
      the basis of maximum standardized uptake value (SUV(max)). BM imaging patterns,
      normal BM, and maximal lesion (11)C-methionine uptake in patients with MM were
      compared with those in control patients. In two patients with MM, sulfur 35
      ((35)S) methionine uptake in freshly isolated BM plasma cells was measured.
      Values for SUV(max) of groups were compared by using the Mann-Whitney test on a
      per-patient basis. RESULTS: (35)S-methionine uptake of plasma cells was five- to
      sixfold higher than in normal BM cells. (11)C-methionine BM uptake in control
      patients was homogeneous and low. All patients with MM except one with
      exclusively extramedullary myeloma had (11)C-methionine-positive lesions. Maximal
      lesion and normal BM (11)C-methionine mean SUV(max) were 10.2 +/- 3.5 and 4.3 +/-
      2.0, respectively, and thus were significantly higher than that of BM in the
      control group (mean, 1.8 +/- 0.3; P < .001). Extramedullary MM was clearly
      visible in three patients (mean SUV(max), 7.2 +/- 2.4). Additional (11)C
      methionine-positive lesions in normal cancellous bone were found in nearly all
      patients with MM. In pretreated patients with MM, a moderate fraction of
      osteolytic lesions had no (11)C-methionine uptake. CONCLUSION: On the basis of
      increased methionine uptake in plasma cells, active MM can be imaged with (11)C
      methionine PET/CT.

PMID- 17179399
TI  - Bronchial measurement with three-dimensional quantitative thin-section CT in
      patients with cystic fibrosis.
AB  - PURPOSE: To prospectively compare bronchial measurements obtained with three
      dimensional quantitative thin-section computed tomography (CT) with those
      obtained with thin-section CT scores in the assessment of the severity of
      pulmonary cystic fibrosis (CF). MATERIALS AND METHODS: Ethics committee approval
      was obtained. Sixteen patients with CF (mean age, 26.6 years; range, 18-42 years)
      and five healthy volunteers (mean age, 27.4 years; range, 21-44 years) gave
      written informed consent, underwent multi-detector row CT and a pulmonary
      function test (PFT), and were divided into three groups: group A, healthy
      volunteers; group B, patients with mild CF (forced expiratory volume in 1 second
      [FEV(1)] > 80%); and group C, patients with severe CF (FEV(1) < 80%). Two
      observers obtained thin-section CT scores with eight scoring systems. Bronchial
      cross-sectional wall area (WA), lumen area (LA), airway area, and wall thickness
      (WT) were measured with customized software and were normalized on the basis of
      subject body surface. Morphologic characteristics, PFT results, thin-section CT
      scores, and quantitative measurements were compared among the three groups with
      analysis of variance. Correlations among bronchial measurements, PFT results, and
      CT scores were calculated with the Spearman correlation coefficient. RESULTS:
      Thin-section CT scores were different between group C and either group A or group
      B (P < .05). WA and WT were significantly different among all groups (P < .05).
      Interscore correlations and correlations between bronchial parameters and scores
      were high (r > 0.89, P < .0001). Scores, WA, and WT were significantly correlated
      with PFT obstructive indexes (P < .047). CONCLUSION: WA and WT assessed with
      dedicated software on multi-detector row CT images allow evaluation of the
      severity of pulmonary CF.

PMID- 17179400
TI  - Intracranial hemorrhage in asymptomatic neonates: prevalence on MR images and
      relationship to obstetric and neonatal risk factors.
AB  - PURPOSE: To retrospectively evaluate the prevalence of neonatal intracranial
      hemorrhage (ICH) and its relationship to obstetric and neonatal risk factors.
      MATERIALS AND METHODS: Pregnant women were recruited for a prospective study of
      neonatal brain development; the study was approved by the institutional review
      board and complied with HIPAA regulations. After informed consent was obtained
      from a parent, neonates were imaged with 3.0-T magnetic resonance (MR) imaging
      without sedation. The images were reviewed by a neuroradiologist with 12 years of
      experience for the presence of ICH. Medical records were prospectively and
      retrospectively reviewed for selected risk factors, which included method of
      delivery, duration of labor, and evidence of maternal or neonatal birth trauma.
      Risk factors were assessed for relationship to ICH by using Fisher exact test
      statistics. RESULTS: Ninety-seven neonates (mean age at MR imaging, 20.8 days +/-
      6.9 [standard deviation]) underwent MR imaging between the ages of 1 and 5 weeks.
      Eighty-eight (44 male and 44 female) neonates (65 with vaginal delivery and 23
      with cesarean delivery) completed the MR imaging evaluation. Seventeen neonates
      with ICHs (16 subdural, two subarachnoid, and six parenchymal hemorrhages) were
      identified. Seven infants had two or more types of hemorrhages. All neonates with
      ICH were delivered vaginally, with a prevalence of 26% in vaginal births. ICH was
      significantly associated with vaginal birth (P < .005) but not with prolonged
      duration of labor or with traumatic or assisted vaginal birth. CONCLUSION:
      Asymptomatic ICH following vaginal birth in full-term neonates appears to be
      common, with a prevalence of 26% in this study.

PMID- 17179401
TI  - Cytotoxicity of iodinated and gadolinium-based contrast agents in renal tubular
      cells at angiographic concentrations: in vitro study.
AB  - PURPOSE: To test in vitro whether gadolinium-based contrast agents induce fewer
      toxic effects on renal tubular cells than does an iodinated contrast medium at
      concentrations used for angiography. MATERIALS AND METHODS: LLC-PK1 cells were
      incubated with iomeprol, gadopentetate dimeglumine, gadobenate dimeglumine,
      gadoterate meglumine, gadodiamide, and corresponding mannitol solutions for 24
      hours at 37 degrees C in two experimental settings: measurements with equally
      attenuating solutions and measurements with equimolar solutions. Cytotoxicity was
      assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)
      assay, trypan blue testing, and an assay to detect apoptosis and necrosis. Data
      were analyzed with analyses of variance and post hoc tests. RESULTS: Yielding the
      same x-ray attenuation, iomeprol-300 and iomeprol-150 at concentrations of 2.34
      18.75 mg of iodine per milliliter induced significantly (P < .001) lower
      inhibition of MTT conversion (74%-102% of undamaged control cells) compared with
      15.63-125.00 mmol/L concentrations of the gadolinium-based agents (mean
      percentages of undamaged control cells: 48%-80%, 50%-87%, 60%-95%, and 56%-92%
      with gadopentetate dimeglumine, gadobenate dimeglumine, gadoterate meglumine, and
      gadodiamide, respectively). At equimolar concentrations (62.5 mmol/L), iomeprol
      190 induced a mean extent of inhibition of MTT conversion (69% of undamaged
      control cells) similar to that induced by gadoterate meglumine (71%) and
      gadodiamide (70%), whereas gadopentetate dimeglumine and gadobenate dimeglumine
      induced stronger effects (63% and 64%, respectively; P < .001). At trypan blue
      testing, there were more dead cells after incubation with 125 mmol/L
      gadopentetate dimeglumine than after incubation with iomeprol-190 (57% vs 19%, P
      < .001). The 125 mmol/L gadopentetate and gadobenate formulations induced more
      necrosis and apoptosis than did gadoterate meglumine, gadodiamide, and iomeprol
      (mean percentage difference between treated and untreated control cells: for
      necrosis, +124%, +95%, +17%, -6%, and +3%, respectively; for apoptosis, +34%,
      +35%, +13%, +4%, and +5%, respectively; P < .001). CONCLUSION: At angiographic
      concentrations, gadolinium-based contrast agents do not induce fewer cytotoxic
      effects on cultured renal tubular cells than does iomeprol.

PMID- 17179403
TI  - Women's use of physical and nonphysical self-defense strategies during incidents
      of partner violence.
AB  - Two incidents of partner violence are investigated using qualitative methodology
      to discover strategies women use to protect themselves and examine women's use of
      violence. Data were collected from 447 women (age 18 or older) from 7 domestic
      violence programs and 5 substance use disorder treatment programs in a midwestern
      state. Women were found to have developed numerous self-protection strategies,
      some using nonphysical means only, others using physical means only, and others
      combining nonphysical and physical means. Women often used a variety of
      strategies in the same incident. Few women initiated violence against partners.
      Implications for theory and research are discussed.

PMID- 17179402
TI  - Exploring couple attributes and attitudes and marital violence in Vietnam.
AB  - Using a couple-centered approach, this study focuses on the relative attributes
      and attitudes of spouses as predictors of marital violence. Analysis of data from
      Vietnam showed that 37% of married women have ever been hit by their husbands.
      Regression results found that husbands with lower resources or status than their
      wives were more likely to have abused. Results also found that the association
      between husbands' gender attitudes and marital violence depends on the level of
      equity of wives'attitudes. The decline in violence among couples in which
      husbands expressed gender equitable attitudes was greater when wives also
      expressed equitable attitudes.

PMID- 17179404
TI  - An evaluation of gender differences in the implementation and impact of a
      comprehensive approach to domestic violence.
AB  - The primary goal of society's response to domestic violence is the protection of
      the victim from further abuse. Recently, the coordinated community response (CCR)
      has been developed as one example of an approach aimed at reaching this goal.
      Prior research has generally found support for the model, with male offenders
      recidivating at lower rates. The current study examines whether a comprehensive,
      community-based approach is capable of reducing recidivism rates among male and
      female offenders. Comparisons are made between 70 female and 131 male offenders.
      Specific attention is given to the intervention process, including differences in
      service or treatment component completion and recidivism by gender.

PMID- 17179405
TI  - Creating lasting attitude and behavior change in fraternity members and male
      student athletes: the qualitative impact of an empathy-based rape prevention
      program.
AB  - Fraternity members and male student athletes responded to open-ended questions
      assessing the impact of an empathy-based rape prevention program. All
      participants reported either lasting attitude or behavior changes; most reported
      both. Participants reported increased understanding of how rape might feel and
      attributed this change to seeing a videotape describing a male-on-male rape
      situation. Participants refrained from telling jokes about rape and reported
      feeling more effective when helping survivors seeking assistance. These behavior
      changes were attributed to the videotape and to a section of the program
      encouraging participants to confront rape jokes and challenge sexist behaviors.

PMID- 17179406
TI  - Collegiate sororities and dating violence: an exploratory study of informal and
      formal helping strategies.
AB  - Women in collegiate sororities are more at risk for violence within the context
      of dating relationships than is the general population of college women. Because
      assaulted women are more likely to turn to their peer networks for support, this
      study explores the formal and informal helping strategies available to sorority
      members within the context of their sororities. A total of 35 women representing
      17 different sororities participated in 4 focus groups. Although the central
      finding uncovered how violence is largely omitted from the formal agendas of
      sororities, community and campus-based programs addressing the issue can build on
      their sincere interest in helping each other.

PMID- 17179408
TI  - A broad view of arsenic.
AB  - In the mind of the general public, the words "arsenic" and "poison" have become
      almost synonymous. Yet, As is a natural metallic element found in low
      concentrations in virtually every part of the environment, including foods.
      Mining and smelting activities are closely associated with As, and the largest
      occurrence of As contamination in the United States is near the gold mines of
      northern Nevada. Inhabitants of Bangladesh and surrounding areas have been
      exposed to water that is naturally and heavily contaminated with As, causing what
      the World Health Organization has described as the worst mass poisoning in
      history. Although readily absorbed by humans, most inorganic As (>90%) is rapidly
      cleared from the blood with a half-life of 1 to 2 h, and 40 to 70% of the As
      intake is absorbed, metabolized, and excreted within 48 h. Arsenic does not
      appreciably bioaccumulate, nor does it biomagnify in the food chain. The United
      States has for some time purchased more As than any other country in the world,
      but As usage is waning, and further reductions appear likely. Arsenic is used in
      a wide variety of industrial applications, from computers to fireworks. All feed
      additives used in US poultry feeds must meet the strict requirements of the US
      Food and Drug Administration Center for Veterinary Medicine (Rockville, MD)
      before use. Although some public health investigators have identified poultry
      products as a potentially significant source of total As exposure for Americans,
      studies consistently demonstrate that <1% of samples tested are above the 0.5 ppm
      limit established by the US Food and Drug Administration Center for Veterinary
      Medicine. Although laboratory studies have demonstrated the possibility that As
      in poultry litter could pollute ground waters, million of tons of litter have
      been applied to the land, and no link has been established between litter
      application and As contamination of ground water. Yet, the fact that <2% of the
      United States population is involved in production agriculture and the overtones
      associated with the word "arsenic" could mean the matter becomes a perception
      issue.

PMID- 17179409
TI  - In vitro effects of deoxynivalenol on small intestinal D-glucose uptake and
      absorption of deoxynivalenol across the isolated jejunal epithelium of laying
      hens.
AB  - Deoxynivalenol (DON) is a common mycotoxin contaminant in feedstuffs. It has been
      shown to cause diverse toxic effects in animals. The aim of the present study was
      to evaluate the effects of DON on the glucose transport capacity in chickens'
      jejunum and to investigate the permeation of DON itself by the Ussing chamber
      technique. Glucose uptake into chicken jejunal epithelia was measured after the
      addition of 200 mumol/L of (14)C-labeled glucose to the mucosal solution. Glucose
      uptake under control condition was 3.28 +/- 0.53 nmol/cm(2) x min. The
      contribution of sodium glucose-linked transporter 1 (SGLT-1) to total glucose
      uptake was estimated by inhibiting SGLT-1 with phlorizin (100 micromol/L). In the
      presence of phlorizin, glucose uptake was reduced (P < 0.05) to 1.21 +/- 0.19
      nmol/cm(2) x min. Deoxynivalenol decreased (P < 0.05) the glucose uptake in the
      absence of phlorizin to 1.81 +/- 0.24 nmol/cm(2) x min but had no additional
      effect on the glucose uptake in the presence of phlorizin (0.97 +/- 0.17
      nmol/cm(2) x min). Mucosal-to-serosal permeation of DON was proportional to the
      initial DON concentration over a concentration range from 1 to 10 mug/mL on the
      mucosal side. Apparent permeability at 10 microg/mL of DON measured 60 to 90 min
      after DON application was 1.7 x 10(-05) cm/s. It can be concluded that DON (10
      mg/L) decreases glucose uptake almost as efficiently as phlorizin. The similarity
      between the effects of phlorizin and DON on glucose uptake evidences their common
      ability to inhibit Na(+)-D-glucose cotransport. In addition to local effects, DON
      can be absorbed from the jejunum. A predominant part of DON passes across the
      chicken intestinal epithelium by passive diffusion, which is likely on the
      paracellular pathway. The results imply that the exposure to DON-contaminated
      feeds may negatively affect animal health and performance by local (i.e.,
      inhibition of intestinal SGLT-1) and systemic effects.

PMID- 17179410
TI  - Comparison of four sampling methods for the detection of Salmonella in broiler
      litter.
AB  - Experiments were conducted to compare litter sampling methods for the detection
      of Salmonella. In experiment 1, chicks were challenged orally with a suspension
      of naladixic acid-resistant Salmonella and wing banded, and additional
      nonchallenged chicks were placed into each of 2 challenge pens. Nonchallenged
      chicks were placed into each nonchallenge pen located adjacent to the challenge
      pens. At 7, 8, 10, and 11 wk of age the litter was sampled using 4 methods: fecal
      droppings, litter grab, drag swab, and sock. For the challenge pens, Salmonella
      positive samples were detected in 3 of 16 fecal samples, 6 of 16 litter grab
      samples, 7 of 16 drag swabs samples, and 7 of 16 sock samples. Samples from the
      nonchallenge pens were Salmonella positive in 2 of 16 litter grab samples, 9 of
      16 drag swab samples, and 9 of 16 sock samples. In experiment 2, chicks were
      challenged with Salmonella, and the litter in the challenge and adjacent
      nonchallenge pens were sampled at 4, 6, and 8 wk of age with broilers remaining
      in all pens. For the challenge pens, Salmonella was detected in 10 of 36 fecal
      samples, 20 of 36 litter grab samples, 14 of 36 drag swab samples, and 26 of 36
      sock samples. Samples from the adjacent nonchallenge pens were positive for
      Salmonella in 6 of 36 fecal droppings samples, 4 of 36 litter grab samples, 7 of
      36 drag swab samples, and 19 of 36 sock samples. Sock samples had the highest
      rates of Salmonella detection. In experiment 3, the litter from a Salmonella
      challenged flock was sampled at 7, 8, and 9 wk by socks and drag swabs. In
      addition, comparisons with drag swabs that were stepped on during sampling were
      made. Both socks (24 of 36, 67%) and drag swabs that were stepped on (25 of 36,
      69%) showed significantly more Salmonella-positive samples than the traditional
      drag swab method (16 of 36, 44%). Drag swabs that were stepped on had comparable
      Salmonella detection level to that for socks. Litter sampling methods that
      incorporate stepping on the sample material while in contact with the litter
      appear to detect Salmonella in greater incidence than traditional sampling
      methods of dragging swabs over the litter surface.

PMID- 17179411
TI  - Recovery of Campylobacter from commercial broiler hatchery trayliners.
AB  - Previous research has identified Campylobacter as one of the leading causes of
      foodborne illness. Poultry and poultry products have been identified as a major
      source of Campylobacter in human infections. Although many risk factors that
      contribute to Campylobacter levels have been identified, precise identification
      of the most effective sites for intervention has not been established.
      Epidemiological studies have identified that Campylobacter in the broiler
      breeder's reproductive tract, fertile eggs, and 2- to 3-wk-old broilers has the
      potential to contaminate day-of-hatch chicks. Numerous studies have shown that
      day-of-hatch broilers are Campylobacter-negative using conventional culture
      methods. The purpose of the present study was to demonstrate the prevalence of
      Campylobacter found in day-of-hatch broilers using a peptone water preenrichment
      followed by conventional Campylobacter culture methods. Using conventional tray
      liner (hatcheries) culture methods, the isolation distribution of Campylobacter
      from 8 commercial broiler hatcheries (n = 2,000) was evaluated. A total of 15
      tray liners were positive from 3 different hatcheries. Of the 2,000 chick paper
      pad tray liners sampled, 0.75% were positive for Campylobacter. These data
      support previous findings indicating the potential for Campylobacter to be spread
      by vertical transmission. This is the first time that Campylobacter has been
      recovered from tray liners collected at commercial broiler hatcheries.

PMID- 17179412
TI  - Estimation of genetic parameters for cumulative egg numbers in a broiler dam line
      by using a random regression model.
AB  - The random regression model (RRM) methodology was applied to the estimation of
      genetic parameters for cumulative egg numbers and monthly egg production in a
      broiler dam line. The data were extracted from records of a commercial dam line
      in 2001 to 2003. A total of 99,193 records from 6,475 hens and 9,111 pedigreed
      animals were used in the current study. The variance components were estimated
      using Gibbs sampling procedure. According to the Bayesian information criterion
      and Bayes factor, an RRM with Legendre polynomial of 2 orders for hatching groups
      and additive genetic effects and of 4 orders for permanent environmental effects
      was chosen as the optimal model for cumulative egg numbers in the broiler dam
      line. The heritability estimates of the cumulative egg numbers between wk 1 and
      40 of production ranged from 0.16 to 0.54, whereas heritability estimates from wk
      12 to 20 of production were moderate. The ratios of permanent environmental
      variance to phenotypic variance were large, indicating that the RRM could produce
      better estimates of additive genetic effects. The genetic and phenotypic
      correlations between cumulative egg numbers at different production weeks
      estimated with the optimal RRM were generally higher when the overlapping weeks
      were greater. In addition, genetic parameters for monthly egg production could
      also be obtained by the optimal RRM, and the heritability estimates ranged from
      0.03 to 0.18. It was suggested that early selection based on cumulative egg
      numbers in the first 19 wk of production could effectively improve annual egg
      production in the broiler dam line.

PMID- 17179414
TI  - Microsatellite marker-based genetic analysis of relatedness between commercial
      and heritage turkeys (Meleagris gallopavo).
AB  - The turkey is second only to the chicken in importance as an agriculturally
      important poultry species. Unlike the chicken, however, genetic studies of the
      turkey continue to be limited. For example, to date, many genomic investigations
      have been conducted to characterize genetic relationships between commercial (CO)
      and non-CO chicken breeds, whereas the nature of the genetic relatedness between
      CO and heritage turkeys remains unknown. The objective of the current research
      was to use microsatellites to analyze the genetic relatedness between CO and
      heritage domestic turkeys including Narragansett, Bourbon Red, Blue Slate,
      Spanish Black, and Royal Palm. Primer pairs specific for 10 previously described
      turkey microsatellite markers were used. The phylogenetic analysis showed that
      the Blue Slate, Bourbon Red, and Narragansett were genetically closely related to
      the CO strain, with a Nei distance of 0.30, and the Royal Palm and Spanish Black
      were the least related to the CO strain, with Nei distances of 0.41 and 0.40,
      respectively. The present work provides a foundation for the basis of using
      heritage turkeys to genetically improve CO populations by introgression.

PMID- 17179413
TI  - Effect of lighting stress on fluctuating asymmetry, heterophil-to-lymphocyte
      ratio, and tonic immobility duration in eleven breeds of chickens.
AB  - The purpose of the present study was to analyze the effect of a lighting stress
      on the fluctuating asymmetry (FA), the heterophil-to-lymphocyte ratio, and the
      tonic immobility duration of chickens. The experiment (440 birds) measured the FA
      of several traits (outer, middle, inner, and hind toe lengths and leg, wing,
      second primary feather, and spur lengths), the heterophil-to-lymphocyte ratio,
      and the tonic immobility duration in 36-wk-old hens and cocks of 8 Spanish breeds
      of chickens (Black-Barred Andaluza, Black-Red Andaluza, Black Castellana, Buff
      Prat, Red-Barred Vasca, Red Villafranquina, Birchen Leonesa, and Blue Leonesa), a
      synthetic breed (Quail Castellana), a White Leghorn population, and the e(y)
      tester line, which had been housed in continuous light (24L:0D) or in a light
      dark regimen (14L:10D) for 16 wk. There was a significant difference between
      lighting treatments in both females and males on the combined FA of the 4 toes (P
      < 0.01) and the combined FA of toe, leg, wing, feather, and spur (in males)
      lengths (P < 0.05), the FA of birds housed under continuous light being greater
      than that of control birds. There was a significant difference (P < 0.001) for
      the heterophil-to-lymphocyte ratio and the tonic immobility duration between
      lighting treatments, the ratio being higher and the duration being longer in the
      group of birds housed under continuous light. Thus, birds exposed to continuous
      light were more stressed and fearful than control hens. Results were consistent
      across the breeds and indicate that a continuous light regimen seriously
      negatively affects the welfare of birds.

PMID- 17179415
TI  - Comparative histopathology of two serotypes of infectious bronchitis virus (T and
      n1/88) in laying hens and cockerels.
AB  - The comparative and sequential histopathology of different tissues of
      unvaccinated laying hens and cockerels were studied in chickens exposed to T and
      N1/88 strain of infectious bronchitis virus (IBV). The Harderian gland and
      trachea of hens and cockerels in both T- and N1/88-infected groups were damaged
      to a similar extent. The cecum was unaffected for both strains of IBV in both
      hens and cockerels. The sequential histopathological changes in hens revealed
      that IBV multiplies initially in the Harderian gland, then in the tracheal mucosa
      and simultaneously in the kidney and regions of the oviduct such as the magnum,
      tubular shell gland, and shell gland pouch. In cockerels, IBV multiplies first in
      the Harderian gland, then simultaneously in the trachea and kidney. Overall, the
      severity and persistence of lesions were greater in the kidneys of T-infected
      hens as compared with N1/88-infected hens. However, pathological changes in the
      kidney were mild in T- and N1/88-infected cockerels.

PMID- 17179416
TI  - Histopathology of two serotypes of infectious bronchitis virus in laying hens
      vaccinated in the rearing phase.
AB  - The comparative histopathology of 2 different strains of infectious bronchitis
      virus (T and N1/ 88) in vaccinated hens was studied at 110 wk of age. The
      Harderian gland showed similar histopathology in T- and N1/88-infected hens. The
      trachea and kidney of challenged vaccinated hens were protected to a moderate
      extent, but the oviduct was protected to only a small extent. The severity and
      persistence of lesions were greater in tubular shell gland, shell gland pouch,
      and kidney of the T-infected hens, whereas, for the magnum, N1/88 had a greater
      effect.

PMID- 17179417
TI  - Influence of Pediococcus-based probiotic on coccidiosis in broiler chickens.
AB  - Coccidiosis is the major parasitic disease of poultry and is caused by the
      apicomplexan parasites Eimeria. Drugs and live vaccines are the 2 main control
      measures of the disease; however, due to increasing concerns with prophylactic
      drug use and the high cost of vaccines, alternative control methods are needed.
      Recent evidence that various dietary and live microbial supplements can influence
      host immunity against enteric diseases prompted us to investigate the role of a
      Pediococcus-based probiotic on coccidiosis in broiler chickens. In the present
      study, we examined BW gains, oocyst shedding, and antibody responses of broilers
      fed the commercial probiotic MitoGrow. Day-old chicks were fed either a regular
      broiler diet or 1 of 2 probiotic diets supplemented with 0.1% (MG 0.1) or 0.2%
      MitoGrow. Chicks were orally challenged with 5,000 or 10,000 sporulated oocysts
      of Eimeria acervulina or with 5,000 Eimeria tenella oocysts on d 10 or 12 of age,
      respectively. In E. acervulina-infected birds, the MG 0.1 group improved (P <
      0.05) weight gain as compared with the other 2 groups and reduced (P < 0.05)
      oocyst shedding in birds infected with 5,000 E. acervulina oocysts. In E. tenella
      infected birds, Eimeria-specific antibody levels were higher (P < 0.05) in the
      Mito-Grow-fed groups, especially in the MG 0.1 birds, compared with the regular
      diet group, although their oocyst shedding and weight gains were not clearly
      improved. These results demonstrate that this Pediococcus acidilactici-based
      probiotic effectively enhances the resistance of birds and partially protects
      against the negative growth effects associated with coccidiosis, particularly
      when supplemented at 0.1% MitoGrow of the diet.

PMID- 17179418
TI  - Characterization of the chicken small intestine type IIb sodium phosphate
      cotransporter.
AB  - Intestinal absorption and renal resorption play a critical role in overall
      phosphorus homeostasis in chickens. Using RNase-ligase-mediated rapid
      amplification of cDNA ends PCR, we obtained a cDNA from the broiler small
      intestine that encodes a type IIb Na-dependent phosphate transporter. The cDNA
      has an open reading frame of 2,022 bp and predicts a 674-amino acid protein with
      a molecular mass of approximately 74 kDa. Prediction of membrane spanning domains
      based on the hydrophilic and hydrophobic properties of the amino acids suggests 8
      transmembrane domains, with both the NH(2) and COOH termini being intracellular.
      The Na-inorganic phosphate (Pi) IIb cotransporter has relative high homology with
      other type II Na-Pi cotransporters but low homology with the type I or type III
      Na-Pi cotransporters. Northern blot analysis demonstrated the presence of a
      single mRNA transcript present predominantly in the small intestine, with the
      highest expression in the duodenum, followed by the jejunum and ileum. In situ
      hybridization indicated that the Na-Pi cotransporter mRNA is expressed throughout
      the vertical cryptvillus axis of the small intestine. Reduction of P in the diet
      of chicks from hatch to 4 d of age resulted in a significant induction of Na-Pi
      cotransporter mRNA expression in the small intestine. Further study is needed to
      elucidate its physiological role in intestinal phosphate absorption in chickens.

PMID- 17179419
TI  - Age-related influence of a cocktail of xylanase, amylase, and protease or phytase
      individually or in combination in broilers.
AB  - This 21-d experiment was conducted to determine if the response of chicks to a
      cocktail of xylanase, amylase, and protease (XAP) or Escherichia coli-derived
      phytase individually or in combination when fed a nutritionally marginal corn
      soybean meal diet is age-dependent. Six hundred 1-d-old chicks were allocated to
      5 dietary treatments in a randomized complete block design. The treatments were
      as follows: 1) positive control with supplemental inorganic P; 2) negative
      control (NC) marginal in P and ME; 3) NC plus XAP to provide (per kg of diet)
      650, 1,650, and 4,000 U of xylanase, amylase, and protease, respectively; 4) NC
      plus phytase added to provide 1,000 phytase units/kg; and 5) NC plus a
      combination of XAP and phytase. Low ME and P in the NC diet depressed weight gain
      and gain:feed (P < 0.001). A cocktail of XAP alone did not improve performance,
      but phytase supplementation improved (P < 0.001) weight gain. The enzymes were
      additive in their effects on growth performance. The enzymes had no effect on
      ileal digestible energy. Ileal N digestibility was higher (P < 0.05) in diet with
      XAP or phytase individually compared with NC. Both phytase and XAP individually
      and in combination improved (P < 0.01) ileal P digestibility compared with NC.
      Total tract nutrient retention and ME increased (P < 0.01) as the birds grew
      older. There were age x diet interactions (P < 0.001) on total tract retention of
      P and Ca; improvement in P retention due to phytase use decreased by 50% as the
      chicks matured. The current study shows that a combination of XAP and phytase
      improved performance, but the enhancement in performance appears to be mainly
      from phytase. Both XAP and phytase were effective in improving P digestibility
      and retention of chicks receiving nutritionally marginal corn-soybean meal. The
      data also shows that the chicks benefited more from the enzyme addition at a
      younger age and that the contribution of the enzymes to nutrient retention
      decreased with age in chickens.

PMID- 17179420
TI  - Growth performance and ileal and total tract amino acid digestibility in broiler
      chickens fed diets containing bacterial protein produced on natural gas.
AB  - A total of 180 broiler chickens were fed 1 of 3 diets from day-old to slaughter
      at 35 d: a control diet with 35% soybean meal (SOY) or diets in which either 6%
      basic bacterial protein meal (BBP) or 6% autolysed bacterial protein meal (AUT)
      partially replaced soybean meal protein. Ileal and total tract apparent amino
      acid digestibility were examined in 5 chickens per diet using TiO(2) as an inert
      marker. Chickens fed the diets with bacterial protein had higher weight gain and
      feed consumption than control chicks during the first 3 wk, but there were no
      differences in growth or feed intake during the last 2 wk or during the total
      experimental period. The birds fed the BBP diet showed more efficient feed
      conversion compared with chickens fed the SOY and AUT diets. Litter quality at 5
      wk was poorer in pens where the chickens were fed the AUT diet compared with the
      other 2 treatments. There were no differences among diets in the dressing
      percentage. Ileal amino acid digestibility at 5 wk of age revealed only minor
      differences between diets. There was a tendency toward lower ileal digestibility
      (0.12 > P > 0.07) of Arg, Lys, Met, and Phe in the AUT diet compared with the SOY
      diet, whereas there were no differences between the SOY and BBP diets. Total
      tract amino acid digestibilities at 5 wk were similar or slightly lower than the
      ileal digestibilities within diets. Total tract amino acid digestibility at 2 wk
      was similar to the total tract amino acid digestibility at 5 wk. The diets
      containing bacterial protein showed lower total tract digestibility of most amino
      acids compared with the SOY diet. It was concluded that 6% of either basic or
      autolysed bacterial protein can replace soybean meal in diets for broiler
      chickens without impairing growth performance, and the basic bacterial protein
      seemed to be a slightly better substitute than the autolysed bacterial protein.

PMID- 17179421
TI  - A comparison of methods to determine amino acid digestibility of feed ingredients
      for chickens.
AB  - Two experiments were conducted to compare standardized ileal amino acid (AA)
      digestibility in 7- and 21-d-old chicks and true AA digestibility as determined
      by the precision-fed cecectomized rooster assay for several ingredients used in
      poultry feeds. Diets were formulated to contain soybean meal, cottonseed meal,
      poultry by-product meal, and fish meal in experiment 1 and corn, wheat, soybean
      meal, poultry by-product meal, feather meal, and fish meal in experiment 2 as the
      sole sources of protein. Celite, used as an indigestible marker, was added at
      1.5% of the diet. The test diets were fed ad libitum to broiler chicks from 0 to
      7 d of age in experiment 1 and from 4 to 7 and 17 to 21 d of age in experiment 2.
      Ileal digesta samples were collected after euthanizing the birds at 7 d of age in
      experiment 1 and at 7 and 21 d of age in experiment 2. Additionally,
      cecectomized, Single-Comb White Leghorn roosters were used for crop intubation of
      the test diets for determination of true AA digestibility. In experiment 1, AA
      digestibility of all ingredients tested was significantly lower at 7 d of age
      than when determined by the rooster assay. In experiment 2, no differences were
      detected between AA digestibility at 7 or 21 d of age in the chick assay for the
      majority of the indispensable AA. However, the AA digestibility coefficients
      obtained by the chick assay at 7 d and, in some cases, at 21 d of age, were
      significantly lower than those obtained by the rooster assay. In conclusion,
      there were differences in the AA digestibility coefficients obtained through the
      chick and the rooster assays. Such discrepancies could be associated with an age
      effect or the methodological differences between both methods.

PMID- 17179422
TI  - An inexpensive, simple protocol for DNA isolation from blood for high-throughput
      genotyping by polymerase chain reaction or restriction endonuclease digestion.
AB  - We describe simple, inexpensive, and reliable methods for isolating DNA from
      avian blood, semen, or feather pulp. The procedures are readily applicable to
      high-throughput 96-well plate isolation for genotype analysis of chicken DNA
      based on restriction endonuclease digestion or PCR. Isolation cost is primarily
      the cost of a deep-well assay block and a few pipet tips; current price is less
      than 0.10 dollar per sample, providing a significant cost advantage over
      commercial kits. The procedure employs inexpensive, nonhazardous reagents and
      yields intact, double-stranded DNA from as little as 2 to 10 microL of avian
      blood, suitable for RFLP analysis or hundreds of PCR amplifications. We compared
      our method to published procedures for alkaline extraction from feather pulp and
      found our method to be more reliable with the advantage of isolating intact DNA
      sequences that can be easily quantified. With minor modifications, the method can
      isolate DNA for PCR genotyping from mammalian whole blood.

PMID- 17179423
TI  - Offspring produced from orthotopic transplantation of chicken ovaries.
AB  - The loss of avian genetic variation and the threat of disease lend urgency to the
      cryopreservation of remaining poultry stocks. However, techniques for freezing
      ova and embryos are not available for birds, and the recovery of genetic material
      has been a major obstacle to cryopreservation. To overcome this problem, we
      transplanted chicken ovarian tissue just after hatch with or without subsequent
      treatment of the recipient with an immunosuppressant. Nine of 12 hens in the
      nonimmunosuppressed group and 6 of 9 birds in the immunosuppressed group produced
      eggs, whereas 3 hens in each group produced donor-derived offspring. These
      results suggest that transplantation of ovarian tissue of chickens is possible if
      performed just after hatch. This finding should allow efficient cryopreservation
      of female germ cells in chickens with regeneration in live birds. In addition,
      ovarian transplantation could be useful for studies in genetics or developmental
      biology or could provide convenient access to the female germline for genetic
      manipulation.

PMID- 17179425
TI  - Dietary inulin affects the morphology but not the sodium-dependent glucose and
      glutamine transport in the jejunum of broilers.
AB  - Inulin, a prebiotic, is a fermentable oligosaccharide that may affect the
      intestinal mucosal architecture and the electrophysiological parameters. The
      effects of a diet with added inulin were tested on the jejunal morphology and
      electrogenic transport of Glc and Gln from the jejunal mucosa in broilers. Short
      circuit current and transmucosal tissue resistance of jejunal flaps were measured
      in Ussing chambers. The feeding experiment was carried out in broilers (n = 40)
      using 1% inulin with an application period of 5 wk. The inulin-containing diet
      resulted in longer jejunal villi (P < 0.05) and deeper crypts (P < 0.01) than in
      control birds without affecting villus:crypt depth. Basal short-circuit current
      value remained unaffected by dietary treatment. Inulin supplementation did not
      modify the electrogenic transport of Glc and Gln in the jejunal mucosa. The basal
      value of transmucosal tissue resistance was significantly lower (P < 0.001) in
      the inulin-fed group compared with the control group. In conclusion, inulin
      supplementation affected the jejunal mucosal architecture but did not modify the
      electrogenic transport of Glc and amino acid under present experimental
      condition.

PMID- 17179424
TI  - Deficiency of growth hormone receptor does not affect male reproduction in dwarf
      chickens.
AB  - Sex-linked dwarf chickens caused by the mutation of the growth hormone receptor
      gene are characterized by normal growth hormone (GH), very low insulin-like
      growth factor I (IGF-I) level in the blood, and reduced growth. It has been
      demonstrated that the sex-linked dwarfing gene has negative effects on female
      reproduction. In the current study, dwarf cocks and their phenotypic normal
      siblings were used to investigate the effects of dwarf gene on male reproduction.
      Dwarf cocks grew slower than the normal cocks did, and at 20 wk of age, their BW
      were 36.4% smaller. However, all parameters for semen quality, including volume,
      sperm concentration, viability, mobility, pH, and percentage of abnormal sperms,
      examined at 30 wk of age showed no significant difference between normal and
      dwarf cocks. The fertility of dwarf cocks was 95.2%, and the normal was 92.4%.
      The concentrations of GH and IGF-I in serum and seminal plasma were measured with
      RIA and ELISA, respectively. The serum GH in the dwarf cocks was significantly
      higher than their normal siblings (P < 0.05), whereas the serum IGF-I in the
      dwarf cocks was very low. However, the concentration of seminal IGF-I in dwarf
      cocks was similar to that of their normal siblings, indicating that IGF-I might
      be produced and acted independently in testis. In conclusion, the deficiency in
      GH receptor did not affect the male reproduction in dwarf chickens, and the
      fertility of dwarf cocks could be satisfactory for production when artificial
      insemination was adopted.

PMID- 17179426
TI  - Spoilage microflora of broiler carcasses washed with electrolyzed oxidizing or
      chlorinated water using an inside-outside bird washer.
AB  - The effect of acidic, electrolyzed oxidizing (EO) water and chlorinated water on
      the spoilage microflora of processed broiler carcasses was examined. Carcasses
      were sprayed for 5 s at 80 psi with tap, chlorinated, or EO water in an inside
      outside bird washer. Treated carcasses were then stored at 4 degrees C for 0, 3,
      7, or 14 d, and the microbial flora of the carcasses was sampled using the whole
      carcass rinse procedure. Populations of psychrotrophic bacteria and yeasts in the
      carcass rinsates were enumerated. Results indicated that immediately after
      spraying the carcasses, significantly fewer psychrotrophic bacteria were
      recovered from carcasses sprayed with chlorinated or EO water than from carcasses
      sprayed with tap water. Furthermore, significantly fewer yeasts were recovered
      from carcasses sprayed with EO water than from carcasses sprayed with tap or
      chlorinated water. The population of psychrotrophic bacteria and yeasts increased
      on all carcasses during refrigerated storage. However, after 14 d of storage,
      significantly fewer psychrotrophic bacteria and yeasts were recovered from
      carcasses sprayed with EO water than from carcasses sprayed with tap or
      chlorinated water, and significantly fewer microorganisms were recovered from
      carcasses sprayed with chlorinated water than from carcasses sprayed with tap
      water. Pseudomonas spp. and Candida spp. were the primary microbial isolates
      recovered from the broiler carcasses. Findings from the present study indicate
      that EO water can effectively be used in inside-outside bird washers to decrease
      the population of spoilage bacteria and yeasts on processed broiler carcasses.

PMID- 17179427
TI  - Effect of genotype on slaughtering performance and meat physical and sensory
      characteristics of organic laying hens.
AB  - Slaughtering yields and some meat physical and sensorial parameters of laying
      hens reared under organic system production were studied. The hens belonged to
      both Italian dual-purpose breeds [Ermellinata di Rovigo (ER; brown eggshell) and
      Robusta Maculata (RM; brown eggshell)] as well as hybrid genotypes [Hy Line White
      36 (white eggshell) and Hy Line Brown (brown eggshell)]. The birds were reared
      under organic farming system production from 24 to 44 wk of age, when they were
      slaughtered. They were reared throughout summer and autumn, and the temperature
      ranged from about 28 to 3 degrees C. Local breeds presented higher (P < 0.01)
      live BW and dressing percentage compared with hybrids. The RM and ER carcasses
      had (P < 0.01) the highest breast and leg (thigh and drumstick) percentage,
      respectively. The muscle-bone ratio of the Hy Line White 36 drumstick was lower
      (P < 0.05) than the RM ratio, whereas the other groups were intermediate. The ER
      breast presented the highest (P < 0.01) lightness value and the lowest (P < 0.01)
      final pH value compared with the other 3 groups. The breast meat significantly
      differed according to genotype for almost all the studied sensorial parameters
      (adhesivity, fibrousness, chewiness, solubility, juiciness, tenderness, shear
      resistance), with the exception of aroma and odor intensity. In the thigh,
      genotype significantly affected aroma, adhesivity, fibrousness, solubility,
      tenderness, and shear resistance.

PMID- 17179428
TI  - Prediction of meatiness and fatness in ducks by using a skin slice with
      subcutaneous fat and carcass weight without skin.
AB  - The experiment was performed on Pekin ducks (A-44 strain; 60 males and 60
      females). The birds were reared to 7 wk of age and fed standard diets ad libitum.
      At the completion of the rearing period, the ducks were killed. The carcasses
      were chilled, and skin slices with s.c. fat were removed by a new method. The
      remaining part of the carcass was dissected into meat, intermuscular fat, and
      bones. The statistical analysis showed that the weight of a skin slice with s.c.
      fat, taken from the carcass surface excluding the forearms and wing tips [skin
      slice with fat (X(2))], and the weight of a carcass without this slice, forearms,
      and wing tips (X(1)) were very good indicators of the content of skin with fat (r
      = 0.99) and meat (r = 0.96), respectively, in a whole carcass. The above traits
      provided the basis for deriving regression equations to estimate the content of
      meat (Y) or skin with s.c. and intermuscular fat (U) in whole carcasses of ducks.
      The following 2 equations may be recommended for practical application: Y = 0.691
      X(1) - 0.77 (S(y) = 21.6 g) U = 1.056 X(2) + 53.32 (S(u) = 10.6 g).

PMID- 17179429
TI  - Microbial composition in bioaerosols of a high-throughput chicken-slaughtering
      facility.
AB  - The microbial composition of the air in various areas of a high-throughput
      chicken-slaughtering facility was investigated. Over a 4-mo period, 6 processing
      areas were sampled, and the influence of environmental factors was monitored. The
      highest counts of microorganisms were recorded in the initial stages of
      processing, comprising the receiving-killing and defeathering areas, whereas
      counts decreased toward the evisceration, air-chilling, packaging, and dispatch
      areas. Maximum microbial counts were as follows: coliforms, 4.9 x 10(3) cfu/m(3);
      Escherichia coli 3.4 x 10(3) cfu/m(3); Bacillus cereus, 5.0 x 10(4) cfu/m(3);
      Staphylococcus aureus, 1.6 x 10(4) cfu/m(3); Pseudomonas aeruginosa, 7.0 x 10(4)
      cfu/m(3); presumptive Salmonella spp., 1.5 x 10(4) cfu/m(3); Listeria
      monocytogenes, 1.6 x 10(4) cfu/m(3); and fungi, 1.4 x 10(4) cfu/m(3). Higher
      counts of airborne microorganisms found in the receiving-killing and defeathering
      areas indicate the importance of controlling microbial levels before processing
      to prevent the spread of organisms downstream. This should limit the risk of
      carrying over contaminants from areas known to generate high counts to areas
      where the final food product is exposed to air and surface contamination.

PMID- 17179430
TI  - Marination of turkey breast fillets to control the growth of Listeria
      monocytogenes and improve meat quality in deli loaves.
AB  - Turkey deli loaves were evaluated using organic marinades in the raw product to
      control the growth of Listeria monocytogenes (LM) and improve meat quality in the
      cooked product. Treatments included sodium tripolyphosphate (STP; 0.45%,
      control), sodium lactate (3%), sodium diacetate (0.25%), sodium citrate (0.75%),
      and sodium lactate (3%)/sodium diacetate (0.25%) combination, all containing 1.5%
      salt. Data collected in the 2 trials included pH; lightness, redness, and
      yellowness; bind ability; cooked meat moisture; oxidation (thiobarbituric acid
      reactive substances); aerobic plate count (d 0 to 80); and sensory evaluation.
      Also, thirty-two slices from each loaf were inoculated with a 10(3) cfu/ mL
      surface inoculum streptomycin-resistant LM cocktail and analyzed for LM levels (d
      0 to 77). The sodium lactate treatment was lower in pH (5.84) postmarination.
      Lactate, citrate, and the combination treatments had significantly lower
      lightness values; lactate, diacetate, and citrate had higher redness values; and
      lactate had lower yellowness values postmarination compared with premarination.
      Cook loss, moisture, and bind ability were higher in the STP treatment. Citrate
      and the combination treatments had lower thiobarbituric acid reactive substances
      on d 3, but there were no differences by d 15. Cohesiveness was significantly
      higher in the STP, lactate, and diacetate treatments, and turkey flavor was more
      intense in the combination treatment. The STP loaves had >10(6) cfu/cm(2) aerobic
      plate count by 14 d, lactate by 20 d, citrate by 40 d, diacetate by 70 d, and
      lactate/diacetate by 74 d. Sodium diacetate, citrate, and lactate/diacetate all
      extended the lag phase of LM. Therefore, acidic marinades applied in the raw
      product do have a negative effect on some cooked product quality attributes but
      do improve shelf life and decrease LM growth by extending the lag phase through
      21 d postmortem.

PMID- 17179431
TI  - The effect of blood removal on oxidation and shelf life of broiler breast meat.
AB  - Blood components, especially hemoglobin, are powerful promoters of lipid
      oxidation and may decrease the shelf life of meat products. Therefore, this study
      examined different slaughter techniques to determine their effects on pH (24 h),
      color (L*a*b* values at 24 h), lipid oxidation, residual hemoglobin concentration
      (24 h), and sensory evaluation (d 1 and 4 postmortem; PM) in broiler breast
      fillets. The treatments included 1) CO(2) slaughter and not bled, 2) no stunning
      and bled, 3) electrical stunning (ES) and bled, 4) CO(2) stunning and bled, and
      5) ES and decapitation. The birds were conventionally processed, and analyses
      were performed at 24 h PM except residual hemoglobin for which the samples were
      frozen (-80 degrees C) until analyses ( < 2 mo). There were no significant
      differences in pH or b* values at 24 h PM among any of the treatments. L* values
      were significantly higher, indicating lighter fillets in the ES and decapitated
      birds compared with the darker fillets from the CO(2) stunned and bled birds. The
      CO(2) slaughter and not bled birds had significantly higher a* values, indicating
      more red color, when compared with the ES and bled and decapitated birds. There
      were no significant differences in the residual hemoglobin contents in the
      broiler breast muscle when comparing all of the treatments except CO(2) slaughter
      and not bled, which was significantly (around 15%) greater. Overall TBA-reactive
      substances (TBARS; raw, cooked at 24 h, and cooked at 72 h PM) indicated that ES
      and bled birds had the lowest TBARS when compared with the remaining treatments.
      Consumer panels detected increased aroma (chicken meaty and warmed-over aromas)
      and flavor (chicken meaty and warmed-over flavors) in not bled samples at 24 h
      PM. By 72 h PM, however, there were no significant differences in aroma or
      flavor. Therefore, different slaughter and bleeding method may affect color and
      sensory properties of the broiler breast fillets, and the ES and decapitation
      method had the most favorable results for sensory quality.

PMID- 17179432
TI  - Cross contamination of turkey carcasses by Salmonella species during
      defeathering.
AB  - Salmonella present on the feathers of live birds could be a source of
      contamination to carcass skin during defeathering. In this study, the possibility
      of transfer of Salmonella from the feathers of live turkeys to carcass tissue
      during the defeathering process at a commercial turkey processing plant was
      investigated. The contribution of scald water and the fingers of the picker
      machines to cross contamination were also examined. Over 4 visits, swab samples
      were collected from 174 randomly selected tagged birds before and after
      defeathering. Two swab samples from the fingers of the picker machines and a
      sample of scald water were also collected during each visit. Detection of
      Salmonella was carried out following standard cultural and identification
      methods. The DNA fingerprints obtained from pulsed field gel electrophoresis of
      Salmonella serotypes isolated before and after defeathering, from scald water,
      and from the fingers of the picker machines were compared to trace cross
      contamination routes. Salmonella prevalence was similar before and after
      defeathering during visits 2 and 3 and significantly increased after defeathering
      during visits 1 and 4. Over the 4 visits, all Salmonella subtypes obtained after
      defeathering were also isolated before defeathering. The results of this study
      suggest that Salmonella was transferred from the feathers to carcass skin during
      each visit. On each visit, the Salmonella subtypes isolated from the fingers of
      the picker machines were similar to subtypes isolated before and after
      defeathering, indicating that the fingers facilitate carcass cross contamination
      during defeathering. Salmonella isolated from scald water during visit 4 was
      related to isolates obtained before and after defeathering, suggesting that scald
      water is also a vehicle for cross contamination during defeathering. By using
      molecular subtyping, this study demonstrated the relationship between Salmonella
      present on the feathers of live turkeys and carcass skin after defeathering,
      suggesting that decontamination procedures applied to the external surfaces of
      live turkeys could reduce Salmonella cross contamination during defeathering.

PMID- 17179433
TI  - Feeding broiler breeder males. 1. Effect of feeding program and dietary crude
      protein during rearing on body weight and fertility of broiler breeder males.
AB  - A 2 x 2 factorial experiment was conducted to compare the effects of 2 male
      broiler breeder feed allocation programs (Concave or Sigmoid) during the rearing
      period to 26 wk of age and the interaction with dietary CP (12 or 17%) on BW and
      fertility. From 0 to 2 wk, all birds received a starter diet, after which, pens
      were randomly assigned to the 4 treatment combinations that ended at 26 wk of
      age. All males were weighed individually at 4, 8, 12, 16, 22, 26, 28, 32, 36, 40,
      48, 52, 56, and 64 wk of age, and fertility was determined weekly from 27 to 32
      wk of age and then every 2 wk to 64 wk of age. At 49 wk of age, the male feed
      allocation for all treatments was increased by 5 g/d. Even when fed the same as
      Sigmoid program males during the production period, males reared on the Concave
      feeding program lost BW from 32 to 40 wk of age and exhibited lower BW from 40 to
      48 wk of age, which corresponded to a more rapid decrease in fertility. The 17%
      CP diet increased BW from 8 to 32 wk of age, but no significant differences were
      subsequently observed. The 12% CP rearing diet improved both weekly and
      cumulative fertility. A significant interaction between rearing feeding program
      and dietary CP during the third quartile period showed that the Concave program
      17% CP diet combination was most negatively affected. The increase in male feed
      allocation at 49 wk restored fertility and caused differences among treatments to
      diminish. These data suggested that BW during the early rearing period did not
      affect fertility, but an increased BW due to either providing fast feed
      increments toward the end of the rearing period (Concave) or feeding a 17% CP
      diet produced males that were unable to sustain fertility after 40 wk of age
      without an appropriate allocation of feed.

PMID- 17179434
TI  - Feeding broiler breeder males. 2. Effect of cumulative rearing nutrition on body
      weight, shank length, comb height, and fertility.
AB  - Two experiments were conducted to evaluate the effects of 2 planes (low and high)
      of cumulative nutrient intake during the rearing period on performance of broiler
      breeder males. The low cumulative nutrition program supplied 29,580 kcal of ME
      and 1,470 g of CP, whereas the high cumulative nutrition program supplied 33,500
      kcal of ME and 1,730 g of CP to photostimulation at 21 wk of age. Two diets
      (LoDiet and HiDiet) were used with a single feeding program in experiment 1. In
      experiment 2, a single diet with 2 feeding programs (LoFeed and HiFeed) was used.
      In experiment 1, the 2 diets were blended from 21 to 24 wk to provide a gradual
      transition to a single common laying breeder diet that was fed during the
      production period. At 21 wk of age in experiment 2, males were divided into light
      or heavy BW groups to complete a 2 x 2 factorial design during the production
      period. The high plane of nutrition increased BW, shank length, and comb height
      during the rearing period, but the differences disappeared after 28 wk of age.
      Retrospective analysis showed that the heavy males at 21 wk of age in experiment
      2 were also the heaviest males at 8 wk of age. Both low plane groups (LoDiet in
      experiment 1 and LoFeed in experiment 2) exhibited better fertility during late
      production. A cumulative nutrient intake during the rearing period of 29,580 kcal
      of ME and 1,470 g of CP was minimally sufficient for subsequent male reproductive
      performance.

PMID- 17179435
TI  - Effect of an acidifying diet combined with zeolite and slight protein reduction
      on air emissions from laying hens of different ages.
AB  - The objectives of the study were to evaluate the effectiveness of a reduced
      emission (RE) diet containing 6.9% of a CaSO(4)-zeolite mixture and slightly
      reduced CP to 21-, 38-, and 59-wk-old Hy-Line W-36 hens (trials 1, 2, and 3,
      respectively) on egg production and emissions of NH(3), H(2)S, NO, NO(2), CO(2),
      CH(4), and non-CH(4) total hydrocarbons as compared with feeding a commercial
      (CM) diet. At each age, 640 hens were allocated, randomly to 8 environmental
      chambers for a 3-wk period. On an analyzed basis, the CM diet contained 18.0,
      17.0, and 16.2% CP and 0.25, 0.18, and 0.20% S in trials 1, 2, and 3, and the RE
      diet contained 17.0, 15.5, and 15.6% CP and 0.99, 1.20, and 1.10% S in trials 1,
      2, and 3. Diets were formulated to contain similar Ca and P contents. Average
      daily egg weight (56.3 g), average daily egg production (81%), average daily feed
      intake (92.4 g), and BW change (23.5 g), across ages, were unaffected by diet (P
      > 0.05) over the study period. Age effects were observed for all performance
      variables and NH(3) emissions (P < 0.05). In trials 1, 2, and 3, daily NH(3)
      emissions from hens fed the RE diets (185.5, 312.2, and 333.5 mg/bird) were less
      than emissions from hens fed the CM diet (255.1, 560.6, and 616.3 mg/bird; P <
      0.01). Daily emissions of H(2)S across trials from hens fed the RE diet were 4.08
      mg/bird compared with 1.32 mg/bird from hens fed the CM diet (P < 0.01). Diet (P
      < 0.05) and age (P < 0.05) affected emissions of CO(2) and CH(4). A diet effect
      (P < 0.01) on NO emissions was observed. No diet or age effects (P > 0.05) were
      observed for NO(2) or non-CH(4) total hydrocarbons. Results demonstrated that
      diet and layer age influence air emissions from poultry operations.

PMID- 17179436
TI  - Modeling the growth and death kinetics of Salmonella in poultry litter as a
      function of pH and water activity.
AB  - Contaminated poultry litter, serving as a reservoir for Salmonella, can be linked
      to both food safety concerns when contaminated birds enter processing plants and
      environmental concerns when used as a fertilizer. Predictive modeling allows for
      the estimation of microbial growth or inactivation as a function of controlling
      environmental growth factors. A study was conducted to observe the combined
      effects of pH and water activity (A(w)) at a constant temperature on Salmonella
      populations in used turkey litter to predict microbial response over time.
      Litter, first pH-adjusted and then inoculated with a 3-strain Salmonella serovar
      cocktail to an initial concentration of approximately 10(7) cfu/g, was placed
      into individual sealed plastic containers with saturated salt solutions for
      controlling A(w). A balanced design including 3 A(w) values (0.84, 0.91, 0.96), 3
      pH values (4, 7, 9), and a constant temperature of 30 degrees C was used, with
      litter samples periodically removed and analyzed for Salmonella populations, pH,
      and A(w). At each combination of environmental factors, the Churchill or
      exponential inactivation mathematical models were used to describe the growth and
      death of Salmonella over time. Salmonella populations exhibited growth
      (approximately 2 log) with little decline up to 42 d in litter environments of pH
      7 and 9 and a A(w) of 0.96. As litter A(w) and pH levels were reduced,
      populations declined, with the most drastic reductions (approximately 5 log in 9
      h) occurring in low-pH (4) and low-A(w) (0.84) environments. Generalized models
      for bacterial growth and death under grouped pH environments were successfully
      developed to predict Salmonella behavior in litter over time. These findings
      suggest that the best management practices and litter treatments that lower
      litter A(w) to < or =0.84 and pH to < or =4 are effective in reducing Salmonella
      populations. The use of a single equation to predict the growth and decline of
      Salmonella populations as a function of pH and A(w) has potential application for
      use in the development of effective pathogen control strategies at the farm
      level.

PMID- 17179437
TI  - Expression of positional candidates for shell thickness in the chicken.
AB  - Expression of 12 positional candidates for QTL affecting shell thickness at 53 wk
      of lay age (ST53) was investigated by real-time PCR in the distal part of chicken
      oviducts (uterus) with a forming eggshell. In the local chicken breed Green
      legged Partridgenous, the complete cDNA CR523443 (ChEST985k21) was downregulated
      with ratio of means 0.49 (P < or = 0.01) in the group with low ST53 (248.6 +/-
      16.62 microm) relative to the group with the highest ST53 (372.4 +/- 2.07
      microm). Expression of this gene was highly correlated (0.85, P < or = 0.01) with
      shell thickness. No significant difference in expression between the 2 groups
      with thick (378.4 +/- 3.65 microm) and thin (227.8 +/- 8.99 microm) shell and no
      significant correlation of expression level with ST53 were detected in Rhode
      Island Red, which could be explained by strict selection to egg quality traits,
      including optimal shell thickness in this commercial layer breed. These data
      suggested that CR523443 was a candidate gene for QTL ST53 in the chicken.

PMID- 17179439
TI  - Task switching after stroke.
AB  - BACKGROUND AND PURPOSE: Task switching is a cognitive skill that may be
      compromised after brain damage. The purposes of this study were to examine task
      switching abilities in the subacute phase after stroke, to determine whether a
      switching task under endogenous or internal control is more difficult than a
      switching task under exogenous or cued control, and to determine whether deficits
      in switching attenuate in the first few months after stroke. SUBJECTS: The
      participants in this study were 46 adults with stroke and 38 adults without
      stroke. METHODS: Subjects performed 2 computer-based switching tasks, an
      alternating task that relied on endogenous control and a cued task that relied on
      exogenous control. Testing was done in subjects' homes at 1 and 3 months after
      stroke and at a 2-month interval for control subjects. Switch costs, or the
      difference between the no-switch condition and the switch condition, were
      calculated for accuracy and response time. RESULTS: Subjects in the stroke group
      had higher switch costs for accuracy than did subjects in the control group. The
      alternating task was more difficult than the cued task, with higher switch costs
      for accuracy and response time. The alternating task was particularly difficult
      for subjects in the stroke group, with high switch costs for accuracy. Both
      groups showed decreased response time switch costs at the second testing session.
      DISCUSSION AND CONCLUSION: Task switching, particularly if under endogenous
      control, is impaired in adults in the subacute phase after stroke. Clinicians
      should be aware of performance deficits that may relate to task switching.

PMID- 17179440
TI  - Performance of physical activities by adolescents with cerebral palsy.
AB  - BACKGROUND AND PURPOSE: Mobility and self-care are important considerations for
      successful transition of adolescents with cerebral palsy to adulthood. The
      purpose of this study was to characterize performance of physical activities from
      the perspective of adolescents themselves. SUBJECTS: The subjects were 156
      adolescents with cerebral palsy, 11.6 to 17.7 years of age. METHODS: A therapist
      completed the Gross Motor Function Classification System (GMFCS). Adolescents
      completed the Activities Scale for Kids-Performance Version (ASKp) twice over a 1
      year period. RESULTS: A repeated-measures analysis of variance indicated a main
      effect for GMFCS level. The main effect for time and the GMFCS level x time
      interaction were not significant. Post hoc comparisons indicated that ASKp scores
      differed among all GMFCS levels. DISCUSSION AND CONCLUSION: Performance of
      physical activities by adolescents with cerebral palsy differed based on GMFCS
      level and did not change over 1 year. The ASKp scores of adolescents in levels II
      through V suggest the need for physical assistance at times throughout the day.
      The results have implications for the role of the physical therapist in
      transition planning.

PMID- 17179441
TI  - Paretic upper-limb strength best explains arm activity in people with stroke.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the
      relationship among variables of upper-limb impairment, upper-limb performance in
      activities of daily living (activity), and engagement in life events and roles
      (participation) in people with chronic stroke. SUBJECTS: The subjects were 93
      community-dwelling individuals with stroke (> or =1 year). METHODS: This study,
      which was conducted in a tertiary rehabilitation center, used a cross-sectional
      design. The main measures of impairment were the Modified Ashworth Scale,
      handheld dynamometry, sensory testing (monofilaments), and the Brief Pain
      Inventory. The main measures of activity were the Chedoke Arm and Hand Activity
      Inventory (CAHAI) and the Motor Activity Log (MAL). The main measure of
      participation was the Reintegration to Normal Living (RNL) Index. RESULTS:
      Paretic upper-limb strength (force-generating capacity) (r=.89, P<.01), grip
      strength (r=.69, P<.01), and tone (resistance to passive movement) (r=-.80,
      P<.01) were the impairment variables that were most strongly related to activity.
      Tone (r=-.23, P<.05) and CAHAI scores (r=.22, P<.05) had a significant, but weak,
      relationship to participation. Upper-limb strength accounted for 87% of the
      variance of the CAHAI scores and 78% of the variance of the MAL scores. In the
      participation models, tone and CAHAI scores accounted for 5% of the variance of
      the RNL Index scores. DISCUSSION AND CONCLUSION: Paretic upper-limb strength had
      the strongest relationship with variables of activity and best explained upper
      limb performance in activities of daily living. Grip strength, tone, and
      sensation also were factors of upper-limb performance in activities of daily
      living. Increased tone and upper-limb performance in activities of daily living
      had a weak relationship with participation.

PMID- 17179442
TI  - Effect of neuromuscular electrical stimulation on ankle swelling in the early
      period after ankle sprain.
AB  - BACKGROUND AND PURPOSE: Neuromuscular electrical stimulation (NMES) is frequently
      used to decrease swelling in the early period after ankle sprain. The purpose of
      this study was to evaluate its effectiveness in this treatment. SUBJECTS: Thirty
      four subjects (11 female, 23 male; mean age=30.2 years) who were recovering from
      ankle sprain participated. METHODS: Outcome measures were ankle-foot volume,
      ankle girth, and self-assessed ankle function. Three testing raining sessions
      occurred within 5 days of injury. Subjects were randomly assigned to 1 of 3
      groups: a group that received NMES treatment, a group that received submotor ES
      treatment (designed to act as a control group), and a group that received sham
      treatment. RESULTS: There were no statistically significant differences among the
      groups for ankle-foot volume and self-assessed ankle function. The statistically
      significant differences for ankle girth may have been compromised due to the
      significantly different values among groups at baseline. Ankle girth measurements
      were shown to be statistically significant from session 1 to session 3 for the
      NMES group but not for the other 2 groups. DISCUSSION AND CONCLUSION: The results
      indicate that NMES, as designed and used in this study, is not effective in
      decreasing ankle-foot volume or increasing self-assessed ankle function in the
      early period after ankle sprain.

PMID- 17179443
TI  - DNA (cytosine-5) methyltransferase inhibitors: a potential therapeutic agent for
      schizophrenia.
AB  - In this issue of Molecular Pharmacology, Kundakovic et al. (p. 644) present
      compelling evidence suggesting that the promoters for reelin and GAD67 are
      coordinately regulated. The regulation occurs at the level of DNA (cytosine-5)
      methylation. Moreover, the authors present evidence suggesting that pharmacologic
      inhibition of DNA methyltransferase results in reversal of methylation, loss of
      methyl-DNA binding proteins and relief of repression. Repression of both reelin
      and GAD67 has been implicated in the pathogenesis of schizophrenia. Therefore,
      these results suggest that the reelin and GAD67 promoters are subject to
      continuous repression by DNA methyltransferase and that inhibitors of DNA
      methyltransferase represent a potential treatment for Schizophrenia.

PMID- 17179445
TI  - The cover. Portrait of a Lady.

PMID- 17179444
TI  - Essential role for class II phosphoinositide 3-kinase alpha-isoform in Ca2+
      induced, Rho- and Rho kinase-dependent regulation of myosin phosphatase and
      contraction in isolated vascular smooth muscle cells.
AB  - The laser confocal fluorescent microscope-based observation of contractile
      responses in green fluorescent protein-expressing differentiated vascular smooth
      muscle cells, combined with the RNA interference-mediated gene-silencing
      technique, allowed us to determine the role of phosphoinositide 3-kinase (PI3K)
      class II alpha-isoform (PI3K-C2alpha) as a novel, Ca2+-dependent regulator of
      myosin light-chain phosphatase (MLCP) and contraction. The Ca2+-ionophore
      ionomycin induced a robust contractile response with an increase in the
      intracellular free Ca2+ concentration ([Ca2+]i). The PI3K-C2alpha-specific short
      interfering RNA (siRNA) induced a selective and marked reduction in PI3K-C2alpha
      protein expression. The siRNA-mediated knockdown of PI3K-C2alpha, but not class I
      PI3K p110alpha, suppressed ionomycin-induced contraction without altering Ca2+
      mobilization. PI3K-C2alpha is uniquely less sensitive to the PI3K inhibitor 2-(4
      morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) than the other PI3K
      members, including p110alpha. Ionomycin-induced contraction was inhibited only by
      a relatively high concentration of LY294002. Consistent with our previous
      observations showing that ionomycin and membrane depolarization induced Rho
      activation in vascular smooth muscle tissues in a Ca2+-dependent manner,
      ionomycin-induced contraction was dependent on Rho and Rho-kinase. Ionomycin
      induced phosphorylation of the MLCP-regulatory subunit myosin targeting protein
      1(MYPT1) at Thr850 and the 20-kDa myosin light chain (MLC) in a Rho kinase
      dependent manner. Knockdown of PI3K-C2alpha suppressed phosphorylation of both
      MYPT1 and MLC. The receptor agonist noradrenaline, which induced a rapid increase
      in the [Ca2+]i and Ca2+-dependent contraction, stimulated phosphorylation of
      MYPT1 and MLC, which was also dependent on Ca2+, PI3K-C2alpha, and Rho-kinase.
      These observations indicate that PI3K-C2alpha is necessary for Ca2+-induced Rho-
      and Rho kinase-dependent negative regulation of MLCP and consequently MLC
      phosphorylation and contraction.

PMID- 17179446
TI  - A piece of my mind. A long time ago.

PMID- 17179447
TI  - Stem cells probed as diabetes treatment.

PMID- 17179448
TI  - Drug therapy for prehypertension questioned.

PMID- 17179449
TI  - New policy puts some newborns at risk: medical groups denounce Medicaid changes.

PMID- 17179450
TI  - Cancer-reducing lifestyle factors probed.

PMID- 17179451
TI  - Acetaminophen and aminotransferase elevations.

PMID- 17179453
TI  - The incidentalome.

PMID- 17179452
TI  - Congestive heart failure and diurnal blood pressure pattern.

PMID- 17179454
TI  - The incidentalome.

PMID- 17179455
TI  - Contraception and prevention of HIV infection.

PMID- 17179456
TI  - Use of children as interpreters.

PMID- 17179458
TI  - Relation between Medicare screening reimbursement and stage at diagnosis for
      older patients with colon cancer.
AB  - CONTEXT: Medicare's reimbursement policy was changed in 1998 to provide coverage
      for screening colonoscopies for patients with increased colon cancer risk, and
      expanded further in 2001 to cover screening colonoscopies for all individuals.
      OBJECTIVE: To determine whether the Medicare reimbursement policy changes were
      associated with an increase in either colonoscopy use or early stage colon cancer
      diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Patients in the Surveillance,
      Epidemiology, and End Results Medicare linked database who were 67 years of age
      and older and had a primary diagnosis of colon cancer during 1992-2002, as well
      as a group of Medicare beneficiaries who resided in Surveillance, Epidemiology,
      and End Results areas but who were not diagnosed with cancer. MAIN OUTCOME
      MEASURES: Trends in colonoscopy and sigmoidoscopy use among Medicare
      beneficiaries without cancer were assessed using multivariate Poisson regression.
      Among the patients with cancer, stage was classified as early (stage I) vs all
      other (stages II-IV). Time was categorized as period 1 (no screening coverage,
      1992-1997), period 2 (limited coverage, January 1998-June 2001), and period 3
      (universal coverage, July 2001-December 2002). A multivariate logistic regression
      (outcome = early stage) was used to assess temporal trends in stage at diagnosis;
      an interaction term between tumor site and time was included. RESULTS:
      Colonoscopy use increased from an average rate of 285/100,000 per quarter in
      period 1 to 889 and 1919/100,000 per quarter in periods 2 (P<.001) and 3 (P vs
      2<.001), respectively. During the study period, 44,924 eligible patients were
      diagnosed with colorectal cancer. The proportion of patients diagnosed at an
      early stage increased from 22.5% in period 1 to 25.5% in period 2 and 26.3% in
      period 3 (P<.001 for each pairwise comparison). The changes in Medicare coverage
      were strongly associated with early stage at diagnosis for patients with proximal
      colon lesions (adjusted relative risk period 2 vs 1, 1.19; 95% confidence
      interval, 1.13-1.26; adjusted relative risk period 3 vs 2, 1.10; 95% confidence
      interval, 1.02-1.17) but weakly associated, if at all, for patients with distal
      colon lesions (adjusted relative risk period 2 vs 1, 1.07; 95% confidence
      interval, 1.01-1.13; adjusted relative risk period 3 vs 2, 0.97; 95% confidence
      interval, 0.90-1.05). CONCLUSIONS: Expansion of Medicare reimbursement to cover
      colon cancer screening was associated with an increased use of colonoscopy for
      Medicare beneficiaries, and for those who were diagnosed with colon cancer, an
      increased probability of being diagnosed at an early stage. The selective effect
      of the coverage change on proximal colon lesions suggests that increased use of
      whole-colon screening modalities such as colonoscopy may have played a pivotal
      role.

PMID- 17179457
TI  - Long-term effects of cognitive training on everyday functional outcomes in older
      adults.
AB  - CONTEXT: Cognitive training has been shown to improve cognitive abilities in
      older adults but the effects of cognitive training on everyday function have not
      been demonstrated. OBJECTIVE: To determine the effects of cognitive training on
      daily function and durability of training on cognitive abilities. DESIGN,
      SETTING, AND PARTICIPANTS: Five-year follow-up of a randomized controlled single
      blind trial with 4 treatment groups. A volunteer sample of 2832 persons (mean
      age, 73.6 years; 26% black), living independently in 6 US cities, was recruited
      from senior housing, community centers, and hospitals and clinics. The study was
      conducted between April 1998 and December 2004. Five-year follow-up was completed
      in 67% of the sample. INTERVENTIONS: Ten-session training for memory (verbal
      episodic memory), reasoning (inductive reasoning), or speed of processing (visual
      search and identification); 4-session booster training at 11 and 35 months after
      training in a random sample of those who completed training. MAIN OUTCOME
      MEASURES: Self-reported and performance-based measures of daily function and
      cognitive abilities. RESULTS: The reasoning group reported significantly less
      difficulty in the instrumental activities of daily living (IADL) than the control
      group (effect size, 0.29; 99% confidence interval [CI], 0.03-0.55). Neither speed
      of processing training (effect size, 0.26; 99% CI, -0.002 to 0.51) nor memory
      training (effect size, 0.20; 99% CI, -0.06 to 0.46) had a significant effect on
      IADL. The booster training for the speed of processing group, but not for the
      other 2 groups, showed a significant effect on the performance-based functional
      measure of everyday speed of processing (effect size, 0.30; 99% CI, 0.08-0.52).
      No booster effects were seen for any of the groups for everyday problem-solving
      or self-reported difficulty in IADL. Each intervention maintained effects on its
      specific targeted cognitive ability through 5 years (memory: effect size, 0.23
      [99% CI, 0.11-0.35]; reasoning: effect size, 0.26 [99% CI, 0.17-0.35]; speed of
      processing: effect size, 0.76 [99% CI, 0.62-0.90]). Booster training produced
      additional improvement with the reasoning intervention for reasoning performance
      (effect size, 0.28; 99% CI, 0.12-0.43) and the speed of processing intervention
      for speed of processing performance (effect size, 0.85; 99% CI, 0.61-1.09).
      CONCLUSIONS: Reasoning training resulted in less functional decline in self
      reported IADL. Compared with the control group, cognitive training resulted in
      improved cognitive abilities specific to the abilities trained that continued 5
      years after the initiation of the intervention. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00298558.

PMID- 17179459
TI  - Cancer incidence before and after kidney transplantation.
AB  - CONTEXT: Immune suppression after organ transplantation is associated with a
      markedly increased risk of nonmelanoma skin cancer and a few virus-associated
      cancers. Although it is generally accepted that other cancers do not occur at
      increased rates, there have been few long-term population-based cohort studies
      performed. OBJECTIVE: To compare the incidence of cancer in patients receiving
      immune suppression after kidney transplantation with incidence in the same
      population in 2 periods before receipt of immune suppression: during dialysis and
      during end-stage kidney disease before renal replacement therapy (RRT). DESIGN,
      SETTING, AND PARTICIPANTS: A population-based cohort study of 28,855 patients
      with end-stage kidney disease who received RRT, with 273,407 person-years of
      follow-up. Incident cancers (1982-2003) were ascertained by record linkage
      between the Australia and New Zealand Dialysis and Transplant Registry and the
      Australian National Cancer Statistics Clearing House. MAIN OUTCOME MEASURE:
      Standardized incidence ratios (SIRs) of cancer, using age-specific, sex-specific,
      calendar year-specific, and state/territory-specific population cancer incidence
      rates. RESULTS: The overall incidence of cancer, excluding nonmelanoma skin
      cancer and those cancers known to frequently cause end-stage kidney disease, was
      markedly increased after transplantation (n = 1236; SIR, 3.27; 95% confidence
      interval [CI], 3.09-3.46). In contrast, cancer incidence was only slightly
      increased during dialysis (n = 870; SIR, 1.35; 95% CI, 1.27-1.45) and before RRT
      (n = 689; SIR, 1.16; 95% CI, 1.08-1.25). After transplantation, cancer occurred
      at significantly increased incidence at 25 sites, and risk exceeded 3-fold at 18
      of these sites. Most of these cancers were of known or suspected viral etiology.
      CONCLUSIONS: Kidney transplantation is associated with a marked increase in
      cancer risk at a wide variety of sites. Because SIRs for most types of cancer
      were not increased before transplantation, immune suppression may be responsible
      for the increased risk. These data suggest a broader than previously appreciated
      role of the interaction between the immune system and common viral infections in
      the etiology of cancer.

PMID- 17179460
TI  - Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis.
AB  - CONTEXT: Epidemiological and experimental evidence suggests that high levels of
      vitamin D, a potent immunomodulator, may decrease the risk of multiple sclerosis.
      There are no prospective studies addressing this hypothesis. OBJECTIVE: To
      examine whether levels of 25-hydroxyvitamin D are associated with risk of
      multiple sclerosis. DESIGN, SETTING, AND PARTICIPANTS: Prospective, nested case
      control study among more than 7 million US military personnel who have serum
      samples stored in the Department of Defense Serum Repository. Multiple sclerosis
      cases were identified through Army and Navy physical disability databases for
      1992 through 2004, and diagnoses were confirmed by medical record review. Each
      case (n = 257) was matched to 2 controls by age, sex, race/ethnicity, and dates
      of blood collection. Vitamin D status was estimated by averaging 25
      hydroxyvitamin D levels of 2 or more serum samples collected before the date of
      initial multiple sclerosis symptoms. MAIN OUTCOME MEASURES: Odds ratios of
      multiple sclerosis associated with continuous or categorical levels (quantiles or
      a priori-defined categories) of serum 25-hydroxyvitamin D within each
      racial/ethnic group. RESULTS: Among whites (148 cases, 296 controls), the risk of
      multiple sclerosis significantly decreased with increasing levels of 25
      hydroxyvitamin D (odds ratio [OR] for a 50-nmol/L increase in 25-hydroxyvitamin
      D, 0.59; 95% confidence interval, 0.36-0.97). In categorical analyses using the
      lowest quintile (<63.3 nmol/L) as the reference, the ORs for each subsequent
      quintile were 0.57, 0.57, 0.74, and 0.38 (P = .02 for trend across quintiles).
      Only the OR for the highest quintile, corresponding to 25-hydroxyvitamin D levels
      higher than 99.1 nmol/L, was significantly different from 1.00 (OR, 0.38; 95%
      confidence interval, 0.19-0.75; P = .006). The inverse relation with multiple
      sclerosis risk was particularly strong for 25-hydroxyvitamin D levels measured
      before age 20 years. Among blacks and Hispanics (109 cases, 218 controls), who
      had lower 25-hydroxyvitamin D levels than whites, no significant associations
      between vitamin D and multiple sclerosis risk were found. CONCLUSION: The results
      of our study suggest that high circulating levels of vitamin D are associated
      with a lower risk of multiple sclerosis.

PMID- 17179461
TI  - Evaluation and management of patients after implantable cardioverter
      defibrillator shock.
AB  - CONTEXT: There has been a tremendous increase in the use of implantable
      cardioverter-defibrillators (ICDs) after several large clinical trials
      demonstrated their ability to effectively reduce mortality in selected
      populations of patients with cardiac disease. Thus, the nonelectrophysiologist
      will often encounter patients who have received an ICD shock. OBJECTIVE: To
      assess options for the evaluation and management of patients who have received an
      ICD shock. EVIDENCE ACQUISITION: Literature search using the PubMed and MEDLINE
      databases to identify articles published from January 1990 to September 2006,
      using the Medical Subject Headings defibrillators, implantable; defibrillators,
      implantable/adverse effects; anti-arrhythmic agents; electric countershock;
      quality of life; tachycardia therapy; algorithm; ventricular
      tachycardia/diagnosis; and supraventricular tachycardia/diagnosis. Case reports
      were excluded and articles were limited to those published in English. Scientific
      statements and guidelines from the American College of Cardiology, the American
      Heart Association, and the Heart Rhythm Society were also reviewed, as were the
      reference lists of retrieved articles, to identify any additional articles for
      inclusion. EVIDENCE SYNTHESIS: There are multiple causes of both appropriate and
      inappropriate ICD shocks. Irrespective of appropriateness, receiving ICD shocks
      substantially impairs a patient's quality of life. A variety of techniques are
      available using ICD programming to reliably limit the occurrence of appropriate
      or inappropriate ICD shocks. Antiarrhythmic medications can also effectively
      reduce the occurrence of shocks. CONCLUSIONS: Through the use of effective ICD
      programming and antiarrhythmic medications, the occurrence of ICD shocks can be
      reduced while maintaining the lifesaving ability of the ICD. A basic
      understanding of the range of available options is fundamental for evaluation and
      management of the patient who has received an ICD shock.

PMID- 17179462
TI  - A systems approach to patient-centered care.

PMID- 17179463
TI  - Behavior-based interventions to enhance cognitive functioning and independence in
      older adults.

PMID- 17179464
TI  - Medicare policy and colorectal cancer screening: will changing access change
      outcomes?

PMID- 17179466
TI  - Chemokine regulation of the inflammatory response to a low-dose influenza
      infection in CCR2-/- mice.
AB  - Influenza virus infections induce chemokines and cytokines, which regulate the
      immune response. The chemokine receptor CCR2 plays an important role in
      macrophage recruitment and in the development of T1 immunity. In the present
      study, we addressed the role of CCR2 in influenza A virus infection. CCR2
      knockout (-/-) mice are protected against influenza A virus infection, despite
      delayed recruitment of macrophages. We show that low-dose influenza infection of
      CCR2-/- mice leads to increased neutrophilia between Days 5 and 10 after
      infection and decreased monocyte/macrophage and CD4(+) T cell recruitment to the
      lungs between Days 5 and 7 after infection. These changes in leukocyte
      recruitment did not result from or cause increased viral titers or delayed viral
      clearance. Neutrophilia in the lungs correlated with increased keratinocyte
      derived chemokine (KC) and/or MIP-2 expression in CCR2-/- mice between Days 5 to
      10 after infection, although the kinetics of neutrophil recruitment was not
      altered. MIP-2 mRNA and protein expression was increased three- to fivefold, and
      KC protein levels were increased two- to threefold in CCR2-/- compared with CCR2
      wild-type mice at Day 5 after infection. This preceded the peak neutrophil
      influx, which occurred 7 days after infection. In vitro studies confirmed that
      MIP-2 and KC accounted for neutrophil chemotactic activity in the bronchoalveolar
      lavage. CCR2 deficiency also resulted in increased MIP-1alpha, MIP-1beta, MCP-1,
      and IFN-inducible protein 10 and decreased RANTES mRNA expression. Furthermore,
      IL-6 and TNF-alpha cytokine production were elevated after infection. These
      studies suggest that CCR2 plays a multifactorial role in the development of the
      immune response to influenza.

PMID- 17179467
TI  - Role of 90-kDa heat shock protein (Hsp 90) and protein degradation in regulating
      neuronal levels of G protein-coupled receptor kinase 3.
AB  - Cellular levels of G protein-coupled receptor kinase (GRK)3 determine the
      sensitivity of the alpha(2A/B)-adrenoceptor (alpha(2)-AR) to agonist-induced down
      regulation. Using human neuroblastoma BE(2)-C cells, this study examines how
      cellular GRK3 levels are affected by several mechanisms reported to influence
      stability and degradation of other GRKs. We first examined the interaction
      between the 90-kDa heat shock protein (Hsp90) and GRK3; Hsp90 reportedly affects
      the maturation and stability of GRK2. In unstimulated cells, GRK3
      coimmunoprecipitates with Hsp90, suggesting a physical interaction. Moreover,
      when GRK3 protein expression was increased by 24-h epinephrine (EPI) treatment,
      Hsp90 protein expression increased with a similar but slightly delayed time
      course. To investigate the influence of Hsp90 on GRK3 protein stability, we
      determined the effect of the Hsp90 inhibitor geldanamycin (GA) on cellular GRK3
      levels. GA eliminated the interaction between Hsp90 with GRK3 and produced a
      rapid, proteasome-mediated, 70% decrease in GRK3 levels within 24 h. To
      investigate the influence of Hsp90 on up-regulation of GRK3 expression, we
      examined the effect of GA on EPI-induced up-regulation. GA reduced the absolute
      increase in GRK3; however, the percentage of increase in GRK3 by EPI was not
      significantly different in the absence versus presence of GA (141 +/- 41 versus
      94 +/- 12%). Finally, we examined the influence of Ca(2+)-activated proteases on
      cellular GRK3. Treatment with the calcium ionophore ionomycin produced a rapid
      decrease in GRK3 levels that was inhibited by the calpain inhibitor calpeptin. In
      conclusion, several mechanisms influence the degradation of GRK3 and therefore
      have the potential to affect GPCR signaling by regulating GRK3 levels in neurons.

PMID- 17179468
TI  - Structural requirements for optimized delivery, inhibition of oxidative stress,
      and antiapoptotic activity of targeted nitroxides.
AB  - Suppression of mitochondrial production of reactive oxygen species is a promising
      strategy against intrinsic apoptosis typical of degenerative diseases. Stable
      nitroxide radicals such as 4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl
      (TEMPOL) and its analogs combine several important features, including
      recycleability, electron acceptance from respiratory complexes, superoxide
      dismutase mimicry, and radical scavenging. Although successful in antioxidant
      protection, their effective concentrations are too high for successful in vivo
      applications. Recently (J Am Chem Soc 127:12460, 2005), we reported that 4-amino
      2,2,6,6-tetramethyl-1-piperidinyloxy, covalently conjugated to a five-residue
      segment of gramicidin S (GS), was integrated into mitochondria and blocked
      actinomycin D (ActD)-induced superoxide generation and apoptosis. Using a model
      of ActD-induced apoptosis in mouse embryonic cells, we screened a library of
      nitroxides to explore structure-activity relationships between their
      antioxidant/antiapoptotic properties and chemical composition and three
      dimensional (3D) structure. High hydrophobicity and effective mitochondrial
      integration are necessary but not sufficient for high antiapoptotic/antioxidant
      activity of a nitroxide conjugate. By designing conformationally preorganized
      peptidyl nitroxide conjugates and characterizing their 3D structure
      experimentally (circular dichroism and NMR) and theoretically (molecular
      dynamics), we established that the presence of the beta-turn/beta-sheet secondary
      structure is essential for the desired activity. Monte Carlo simulations in model
      lipid membranes confirmed that the conservation of the d-Phe-Pro reverse turn in
      hemi-GS analogs ensures the specific positioning of the nitroxide moiety at the
      mitochondrial membrane interface and maximizes their protective effects. These
      new insights into the structure-activity relationships of nitroxide-peptide and 
      peptide isostere conjugates are instrumental for development of new mechanism
      based therapeutically effective agents.

PMID- 17179469
TI  - Rapid suppression of plasma testosterone levels and tumor growth in the dunning
      rat model treated with degarelix, a new gonadotropin-releasing hormone
      antagonist.
AB  - Degarelix (FE 200486) is a member of a new class of water-soluble (>50 mg/ml)
      gonadotropin-releasing hormone (GnRH) antagonists in clinical development for
      prostate cancer. Upon subcutaneous administration, degarelix forms a gel that
      results in a sustained release of the compound into the circulation, immediately
      blocking GnRH receptors in the pituitary and inducing a fast and sustained
      suppression of gonadotrophin secretion in rats and primates. One of the few
      animal models of prostate adenocarcinoma is the Dunning R-3327H rat carcinoma
      transplanted into Copenhagen rats. The growth of the Dunning tumor can be
      inhibited by various treatments reported to be effective in the clinic, such as
      GnRH superagonists, antiandrogens, 5-alphareductase inhibitors, tyrosine kinase
      inhibitors, and surgical castration. We report in this study that degarelix
      produces a fast and sustained suppression of the pituitary gonadal axis in rats
      and a similar inhibition of tumor growth compared with surgical castration in the
      Dunning R-3327H rat carcinoma model. First, degarelix as been compared with d
      Trp(6)-luteinizing hormone-releasing hormone and surgical castration on a short
      term study (2 months); and second, degarelix has been compared with leuprolide
      and surgical castration on a long-term study (12 months). In both studies,
      degarelix demonstrated a sustained inhibition of tumor growth at least comparable
      with surgical castration. These data provide a convincing profile of degarelix as
      a potential candidate for the clinical management of sex steroid-dependent
      pathologies, such as prostate cancer, where long-term reversible chemical
      castration is required.

PMID- 17179470
TI  - Dietary fat and breast cancer: contributions from a survival trial.

PMID- 17179471
TI  - Cancer stem cells and radiotherapy: new insights into tumor radioresistance.

PMID- 17179472
TI  - Tumor complexity prompts caution about sequencing.

PMID- 17179473
TI  - Lack of progress in teen and young adult cancers concerns researchers, prompts
      study.

PMID- 17179474
TI  - 5-year survival data not always a good measure of progress.

PMID- 17179475
TI  - Stat bite: Breast cancer in young U.S. women.

PMID- 17179476
TI  - E-prescribing first step to improved safety.

PMID- 17179477
TI  - The European Commission may network tissue banks to boost cancer research,
      promote cooperation.

PMID- 17179479
TI  - The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation.
AB  - BACKGROUND: If cancer arises and is maintained by a small population of cancer
      initiating cells within every tumor, understanding how these cells react to
      cancer treatment will facilitate improvement of cancer treatment in the future.
      Cancer-initiating cells can now be prospectively isolated from breast cancer cell
      lines and tumor samples and propagated as mammospheres in vitro under serum-free
      conditions. METHODS: CD24(-/low)/CD44+ cancer-initiating cells were isolated from
      MCF-7 and MDA-MB-231 breast cancer monolayer cultures and propagated as
      mammospheres. Their response to radiation was investigated by assaying clonogenic
      survival and by measuring reactive oxygen species (ROS) levels, phosphorylation
      of the replacement histone H2AX, CD44 levels, CD24 levels, and Notch-1 activation
      using flow cytometry. All statistical tests were two-sided. RESULTS: Cancer
      initiating cells were more resistant to radiation than cells grown as monolayer
      cultures (MCF-7: monolayer cultures, mean surviving fraction at 2 Gy [SF(2Gy)] =
      0.2, versus mammospheres, mean SF(2Gy) = 0.46, difference = 0.26, 95% confidence
      interval [CI] = 0.05 to 0.47; P = .026; MDA-MB-231: monolayer cultures, mean
      SF(2Gy) = 0.5, versus mammospheres, mean SF(2Gy) = 0.69, difference = 0.19, 95%
      CI = -0.07 to 0.45; P = .09). Levels of ROS increased in both mammospheres and
      monolayer cultures after irradiation with a single dose of 10 Gy but were lower
      in mammospheres than in monolayer cultures (MCF-7 monolayer cultures: 0 Gy, mean
      = 1.0, versus 10 Gy, mean = 3.32, difference = 2.32, 95% CI = 0.67 to 3.98; P =
      .026; mammospheres: 0 Gy, mean = 0.58, versus 10 Gy, mean = 1.46, difference =
      0.88, 95% CI = 0.20 to 1.56; P = .031); phosphorylation of H2AX increased in
      irradiated monolayer cultures, but no change was observed in mammospheres.
      Fractionated doses of irradiation increased activation of Notch-1 (untreated,
      mean = 10.7, versus treated, mean = 15.1, difference = 4.4, 95% CI = 2.7 to 6.1,
      P = .002) and the percentage of the cancer stem/initiating cells in the
      nonadherent cell population of MCF-7 monolayer cultures (untreated, mean = 3.52%,
      versus treated, mean = 7.5%, difference = 3.98%, 95% CI = 1.67% to 6.25%, P =
      .009). CONCLUSIONS: Breast cancer-initiating cells are a relatively
      radioresistant subpopulation of breast cancer cells and increase in numbers after
      short courses of fractionated irradiation. These findings offer a possible
      mechanism for the accelerated repopulation of tumor cells observed during gaps in
      radiotherapy.

PMID- 17179478
TI  - Dietary fat reduction and breast cancer outcome: interim efficacy results from
      the Women's Intervention Nutrition Study.
AB  - BACKGROUND: Preclinical and observational studies suggest a relationship between
      dietary fat intake and breast cancer, but the association remains controversial.
      We carried out a randomized, prospective, multicenter clinical trial to test the
      effect of a dietary intervention designed to reduce fat intake in women with
      resected, early-stage breast cancer receiving conventional cancer management.
      METHODS: A total of 2437 women were randomly assigned between February 1994 and
      January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n
      = 1462) groups. An interim analysis was performed after a median follow-up of 60
      months when funding for the intervention ceased. Mean differences between dietary
      intervention and control groups in nutrient intakes and anthropometric variables
      were compared with t tests. Relapse-free survival was examined using Kaplan-Meier
      analysis, stratified log-rank tests, and Cox proportional hazards models.
      Statistical tests were two-sided. RESULTS: Dietary fat intake was lower in the
      intervention than in the control group (fat grams/day at 12 months, 33.3 [95%
      confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7],
      respectively; P<.001), corresponding to a statistically significant (P = .005), 6
      pound lower mean body weight in the intervention group. A total of 277 relapse
      events (local, regional, distant, or ipsilateral breast cancer recurrence or new
      contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the
      dietary group and 181 of 1462 (12.4%) women in the control group. The hazard
      ratio of relapse events in the intervention group compared with the control group
      was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034
      for adjusted Cox model analysis). Exploratory analyses suggested a differential
      effect of the dietary intervention based on hormonal receptor status.
      CONCLUSIONS: A lifestyle intervention reducing dietary fat intake, with modest
      influence on body weight, may improve relapse-free survival of breast cancer
      patients receiving conventional cancer management. Longer, ongoing
      nonintervention follow-up will address original protocol design plans, which
      called for 3 years of follow-up after completion of recruitment.

PMID- 17179480
TI  - Cost-utility analysis of short- versus long-course palliative radiotherapy in
      patients with non-small-cell lung cancer.
AB  - BACKGROUND: Radiotherapy can effectively palliate the symptoms of poor-prognosis
      patients with non-small-cell lung cancer. However, controversy remains about
      whether short-course or more protracted radiotherapy schedules provide better
      value for the money. We conducted a societal cost-utility analysis of a Dutch
      multicenter randomized trial with 1-year follow-up that compared the efficacy of
      radiotherapy schedules consisting of 10 fractions of 3 Gy (10 x 3 Gy) versus two
      fractions of 8 Gy (2 x 8 Gy) in 297 patients with inoperable stage IIIA/B or
      stage IV non-small-cell lung cancer. this trial found that the 10 x 3-Gy group
      had better survival than the 2 x 8-Gy group. METHODS: Lifetime quality-adjusted
      life-years (QALYs) were estimated using the EuroQol questionnaire. Lifetime
      societal costs were estimated using a model estimated based on data from cost
      questionnaires filled out by a subset of patients (n = 56). Differences were
      analyzed statistically using two-sided nonparametric bootstrapping. RESULTS:
      Compared with the 2 x 8-Gy group, the 10 x 3-Gy group accrued statistically
      significantly more QALYs (20.0 versus 13.2 weeks; difference = 6.8 weeks, 95%
      confidence interval [CI] = 0.1 to 13.5 weeks, P = .05), which was mainly due to
      the statistically significantly better survival (38.1 versus 27.4 weeks;
      difference = 10.7 weeks, 95% CI = 0.9 to 20.6 weeks, P = .03) without a
      statistically significant difference with respect to the average valuation of
      health (P = .27). Total radiotherapy and radiotherapy-related costs were
      estimated at 5236 dollars for the 10 x 3-Gy group and 2512 dollars for the 2 x 8
      Gy group (difference = 2724 dollars, 95% CI = 2501 dollars to 2947 dollars,
      P<.001). The 39% increase in life expectancy in the 10 x 3-Gy group as compared
      with the 2 x 8-Gy group was associated with a 30% increase in survival-related
      nonradiotherapy costs (11,254 dollars versus 8651 dollars, difference 2602
      dollars, 95% CI = -357 dollars to 5562 dollars, P = .09). The cost-utility ratio
      for the 10 x 3-Gy schedule versus the 2 x 8-Gy schedule was estimated at 40,900
      dollars per QALY (95% CI = 19,400 dollars to 1,100,000 dollars per QALY).
      CONCLUSIONS: In these poor-prognosis non-small-cell lung cancer patients, the
      estimated cost-utility ratio for the palliative 10 x 3-Gy schedule was acceptable
      according to current economic standards. However, the additional costs for the
      protracted schedule were justified not by improved quality of life but by longer
      survival.

PMID- 17179481
TI  - Radiation-induced leukemia at doses relevant to radiation therapy: modeling
      mechanisms and estimating risks.
AB  - BACKGROUND: Because many cancer patients are diagnosed earlier and live longer
      than in the past, second cancers induced by radiation therapy have become a
      clinically significant issue. An earlier biologically based model that was
      designed to estimate risks of high-dose radiation-induced solid cancers included
      initiation of stem cells to a premalignant state, inactivation of stem cells at
      high radiation doses, and proliferation of stem cells during cellular
      repopulation after inactivation. This earlier model predicted the risks of solid
      tumors induced by radiation therapy but overestimated the corresponding leukemia
      risks. METHODS: To extend the model to radiation-induced leukemias, we analyzed-
      in addition to cellular initiation, inactivation, and proliferation--a
      repopulation mechanism specific to the hematopoietic system: long-range migration
      through the blood stream of hematopoietic stem cells (HSCs) from distant
      locations. Parameters for the model were derived from HSC biologic data in the
      literature and from leukemia risks among atomic bomb survivors who were subjected
      to much lower radiation doses. RESULTS: Proliferating HSCs that migrate from
      sites distant from the high-dose region include few preleukemic HSCs, thus
      decreasing the high-dose leukemia risk. The extended model for leukemia provides
      risk estimates that are consistent with epidemiologic data for leukemia risk
      associated with radiation therapy over a wide dose range. For example, when
      applied to an earlier case-control study of 110,000 women undergoing radiotherapy
      for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for
      leukemia among women who received a large inhomogeneous fractionated external
      beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR
      (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11
      cases observed). As a corresponding example for brachytherapy, the predicted ERR
      of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone
      marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% CI = -0.2
      to 1.9). CONCLUSIONS: An extended, biologically based model for leukemia that
      includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia,
      long-range HSC migration predicts, with reasonable accuracy, risks for radiation
      induced leukemia associated with exposure to therapeutic doses of radiation.

PMID- 17179483
TI  - Statin drugs and risk of advanced prostate cancer.
AB  - BACKGROUND: Statins are commonly used cholesterol-lowering drugs that have
      proapoptotic and antimetastatic activities that could affect cancer risk or
      progression. Results from previous epidemiologic studies of the association
      between statin use and cancer have been inconsistent. We investigated the
      association of statin use with total and advanced prostate cancer, the latter
      being the most important endpoint to prevent. METHODS: We analyzed data from an
      ongoing prospective cohort study of 34,989 US male health professionals who were
      cancer free in 1990 and were followed to 2002. Participants reported their use of
      cholesterol-lowering drugs on biennial questionnaires. Prostate cancer diagnosis
      was confirmed by medical record review. Multivariable-adjusted relative risks
      (RRs) were estimated from Cox proportional hazards regression models. Statistical
      tests were two-sided. RESULTS: During 376,939 person-years of follow-up, we
      ascertained 2579 prostate cancer cases, 316 of which were advanced (regionally
      invasive, metastatic, or fatal). The age-standardized incidence rates of advanced
      prostate cancer were 38 and 89 per 100,000 person-years in current statin users
      and in past or never users, respectively. The multivariable-adjusted relative
      risk of advanced disease was 0.51 (95% confidence interval [CI] = 0.30 to 0.86)
      and of metastatic or fatal disease was 0.39 (95% CI = 0.19 to 0.77) for current
      statin use compared with no current use. The associations remained after
      adjusting for prostate-specific antigen screening history (advanced disease: RR =
      0.57, 95% CI = 0.30 to 1.11; metastatic or fatal disease: RR = 0.35, 95% CI =
      0.14 to 0.92). Risk of advanced disease was lower with longer statin use
      (P(trend) = .003); compared with never use, the relative risk for less than 5
      years of use was 0.60 (95% CI = 0.35 to 1.03) and for 5 or more years of use was
      0.26 (95% CI = 0.08 to 0.83). We found no association between statin use and risk
      of total prostate cancer (RR = 0.96, 95% CI = 0.85 to 1.09). CONCLUSIONS: In this
      cohort of male health professionals, use of statin drugs was not associated with
      risk of prostate cancer overall but was associated with a reduced risk of
      advanced (especially metastatic or fatal) prostate cancer.

PMID- 17179482
TI  - Effect of cromolyn on S100P interactions with RAGE and pancreatic cancer growth
      and invasion in mouse models.
AB  - BACKGROUND: We previously found that S100P, a member of the S100 protein family,
      is expressed in more than 90% of pancreatic tumors and is associated with tumor
      growth and invasion. In the current study, we investigated the ability of the
      antiallergy drug, cromolyn, to block S100P function. METHODS: Interactions
      between cromolyn and S100P were investigated using a drug affinity column and by
      examining cromolyn's effects on coimmunoprecipitation of S100P and receptor for
      advanced glycation end-products (RAGE). The effects of cromolyn on cell growth,
      invasion, and nuclear factor-kappaB (NFkappaB) activity of pancreatic cancer
      cells with (BxPC-3 and MPanc-96) and without (Panc-1) endogenous S100P were
      investigated by cell proliferation assay, by cell invasion assay, and by
      luciferase reporter gene assay, respectively. The effects of cromolyn on tumor
      growth in vivo were investigated in three orthotopic models (n = 20 mice per
      model) by administration of cromolyn (5 mg/kg body weight, daily) with and
      without gemcitabine (125 mg/kg body weight, biweekly), the drug currently used to
      treat pancreatic cancer. Tumor growth was assayed by reporter gene expression.
      All statistical tests were two-sided. RESULTS: S100P was retained on a cromolyn
      affinity column. Cromolyn blocked the coimmunoprecipitation of S100P and RAGE. In
      vitro, cromolyn (100 microM) inhibited S100P-stimulated Panc-1 cell proliferation
      (S100P, mean = 0.93 U, versus S100P + cromolyn, mean = 0.56 U, difference = 0.37
      U; 95% confidence interval [CI] = 0.24 to 0.49 U; P = .001, n = 3), invasion
      (S100P, mean = 58.0%, versus S100P + cromolyn, mean = 9.4%, difference = 48.6%;
      95% CI = 38.8% to 58.8%; P<.001, n = 3), and NFkappaB activity (S100P, mean =
      14,460, versus S100P + cromolyn, mean = 7360 photons/s, difference = 7100
      photons/s; 95% CI = 3689 to 10 510 photons/s; P = .005, n = 3). In vivo, cromolyn
      inhibited tumor growth in mice bearing tumor with endogenous S100P (BxPC-3:
      control, mean = 1.6 x 10(9) photons/s, versus cromolyn, mean = 4.4 x 10(8)
      photons/s, difference = 1.2 x 10(9) photons/s; 95% CI = 6.2 x 10(8) to 1.6 x
      10(9) photons/s; P<.001, n = 5; MPanc-96: control, mean = 1.1 x 10(10) photons/s,
      versus cromolyn, mean = 4.8 x 10(9) photons/s, difference = 6.2 x 10(9)
      photons/s; 95% CI = 1.9 x 10(9) to 1.0 x 10(10) photons/s; P = .009, n = 5) and
      increased the effectiveness of gemcitabine (BxPC-3: gemcitabine, mean = 9.2 x
      10(8) photons/s, versus combination, mean = 1.8 x 10(8) photons/s, difference =
      7.4 x 10(8) photons/s; 95% CI = 4.5 x 10(8) to 1.0 x 10(9) photons/s; P<.001;
      MPanc-96: gemcitabine, mean = 4.1 x 10(9) photons/s, versus combination, mean =
      2.0 x 10(9) photons/s, difference = 2.1 x 10(9) photons/s; 95% CI = 4.4 x 10(8)
      to 3.8 x 10(9) photons/s; P<.001). However, cromolyn had no effect on growth of
      tumors lacking S100P (Panc-1). CONCLUSION: Cromolyn binds S100P, prevents
      activation of RAGE, inhibits tumor growth, and increases the effectiveness of
      gemcitabine in experimental models.

PMID- 17179484
TI  - Re: Frequency and cost of chemotherapy-related serious adverse effects in a
      population sample of women with breast cancer.

PMID- 17179485
TI  - Re: Incidence of initial local therapy among men with lower-risk prostate cancer
      in the United States.

PMID- 17179486
TI  - Body mass index, weight change, and risk of prostate cancer in the Cancer
      Prevention Study II Nutrition Cohort.
AB  - BACKGROUND: Obesity has been associated with aggressive prostate cancer. The
      extent of this association, which varies by stage and grade, remains unclear. The
      role of recent weight change had not been previously examined. METHODS: We
      examined body mass index (BMI) and weight change in relation to incident prostate
      cancer by disease stage and grade at diagnosis among 69,991 men in the Cancer
      Prevention Study II Nutrition Cohort. Participants provided information on height
      and weight in 1982, and again at enrollment in 1992. During follow-up through
      June 30, 2003 (excluding the first 2 years of follow-up), we documented 5,252
      incident prostate cancers. Cox proportional hazards models were used to estimate
      rate ratios (RR) and 95% confidence intervals (95% CI). RESULTS: The association
      between BMI in 1992 and risk of prostate cancer differed by stage and grade at
      diagnosis. BMI was inversely associated with risk of nonmetastatic low-grade
      prostate cancer (RR, 0.84; 95% CI, 0.66-1.06), but BMI was positively associated
      with risk of nonmetastatic high-grade prostate cancer (RR, 1.22; 95% CI, 0.96
      1.55) and risk of metastatic or fatal prostate cancer (RR, 1.54; 95% CI, 1.06
      2.23). Compared with weight maintenance, men who lost >11 pounds between 1982 and
      1992 were at a decreased risk of nonmetastatic high-grade prostate cancer (RR,
      0.58; 95% CI, 0.42-0.79). CONCLUSION: Obesity increases the risk of more
      aggressive prostate cancer and may decrease either the occurrence or the
      likelihood of diagnosis of less-aggressive tumors. Men who lose weight may reduce
      their risk of prostate cancer.

PMID- 17179487
TI  - Obesity is negatively associated with prostate-specific antigen in U.S. men, 2001
      2004.
AB  - BACKGROUND: Recent studies have shown a negative association between body mass
      index (BMI) and prostate-specific antigen (PSA), a commonly used serum marker for
      the detection and diagnosis of prostate cancer. We have examined the association
      between several anthropometric measures and PSA in a nationally representative
      sample of men. METHODS: We analyzed data from the 2001-2004 National Health and
      Nutrition Examination Survey. Participants in this study were men ages >or=40
      years without previously diagnosed prostate cancer who had PSA measured. Height,
      weight, waist circumference, BMI, triceps skinfold, subscapular skinfold, and
      calculated total body water were examined categorically by quintiles using
      multiple linear regression models. All tests of significance were two sided.
      RESULTS: Among white men, we report a trend for decreasing PSA with increasing
      weight, BMI, waist circumference, triceps skinfold thickness, and calculated
      total body water. Among Mexican American men, we found a trend for decreasing PSA
      with increasing BMI, and among black men we found a trend for decreasing PSA with
      increasing triceps thickness. None of the interaction terms between
      race/ethnicity and any of the anthropometric measures were statistically
      significant. Controlling for age and race/ethnicity in the multiple linear
      regression model, we found moderate declines in PSA with a 1 SD increase in BMI
      [5.9% decrease (95% confidence interval, -9.0% to -2.8%) in geometric mean PSA
      per 5.2-unit increase], weight [5.9% decline (-8.8% to -2.8%) per 17.7-kg
      increase], waist circumference [6.6% decline (-9.4% to -3.6%) per 13.4-cm
      increase], triceps skinfold [5.4% decline (-8.9% to -1.8%) per 6.4-mm increase],
      and calculated total body water [5.7% decline (-8.9% to -2.4%) per 6.5-liter
      increase]. CONCLUSION: Our population-based, nationally representative results
      expand the validity of previous studies on obesity and PSA. Higher weight, BMI,
      waist circumference, triceps skinfold, and total body water are associated with
      moderately lower PSA values. A prospective study is needed to verify whether this
      association affects the accuracy of the PSA test in obese men.

PMID- 17179488
TI  - Physical activity and breast cancer risk: the European Prospective Investigation
      into Cancer and Nutrition.
AB  - There is convincing evidence for a decreased risk of breast cancer with increased
      physical activity. Uncertainties remain, however, about the role of different
      types of physical activity on breast cancer risk and the potential effect
      modification for these associations. We used data from 218,169 premenopausal and
      postmenopausal women from nine European countries, ages 20 to 80 years at study
      entry into the European Prospective Investigation into Cancer and Nutrition.
      Hazard ratios (HR) from multivariate Cox regression models were calculated using
      metabolic equivalent value-based physical activity variables categorized in
      quartiles, adjusted for age, study center, education, body mass index, smoking,
      alcohol use, age at menarche, age at first pregnancy, parity, current oral
      contraceptive use, and hormone replacement therapy use. The physical activity
      assessment included recreational, household, and occupational activities. A total
      physical activity index was estimated based on cross-tabulation of these separate
      types of activity. During 6.4 years of follow-up, 3,423 incident invasive breast
      cancers were identified. Overall, increasing total physical activity was
      associated with a reduction in breast cancer risk among postmenopausal women
      (P(trend) = 0.06). Specifically, household activity was associated with a
      significantly reduced risk in postmenopausal (HR, 0.81; 95% confidence interval,
      0.70-0.93, highest versus the lowest quartile; P(trend) = 0.001) and
      premenopausal (HR, 0.71; 95% confidence interval, 0.55-0.90, highest versus
      lowest quartile; P(trend) = 0.003) women. Occupational activity and recreational
      activity were not significantly related to breast cancer risk in both
      premenopausal and postmenopausal women. This study provides additional evidence
      for a protective effect of physical activity on breast cancer risk.

PMID- 17179489
TI  - Intermediate filaments as signaling platforms.
AB  - Intermediate filaments (IFs) are cytoskeletal structures that are crucial for
      maintaining the structural and mechanical integrity of cells and tissues.
      Intriguingly, a wide range of previously unknown nonmechanical roles for the IF
      cytoskeleton are emerging: Recent studies have linked IFs to the integration of
      signals related to the determination of cell size, the regulation of cell
      migration and cell survival, and the buffering of the effects of stress-activated
      kinases. The characteristic structural features and expression patterns of the
      different members of this diverse family of highly abundant proteins make them
      well suited to act as cell- and tissue-specific modifiers and organizers of
      signaling.

PMID- 17179490
TI  - From fluctuations to phenotypes: the physiology of noise.
AB  - There are fundamental physical reasons why biochemical processes might be subject
      to noise and stochastic fluctuations. Indeed, it has long been understood that
      random molecular-scale mechanisms, such as those that drive genetic mutation, lie
      at the heart of population-scale evolutionary dynamics. What we can now
      appreciate is how stochastic fluctuations inherent in biochemical processes
      contribute to cellular and organismal phenotypes. Advancements in techniques for
      empirically measuring single cells and in corresponding theoretical methods have
      enabled the rigorous design and interpretation of experiments that provide
      incontrovertible proof that there are important endogenous sources of
      stochasticity that drive biological processes at the scale of individual
      organisms. Recently, some studies have progressed beyond merely ascertaining the
      presence of noise in biological systems; they trace its role in cellular
      physiology as it is passed through and processed by the biomolecular pathways
      from the underlying origins of stochastic fluctuations in random biomolecular
      interactions to their ultimate manifestations in characteristic species
      phenotypes. These emerging results suggest new biological network design
      principles that account for a constructive role played by noise in defining the
      structure, function, and fitness of biological systems. They further show that
      stochastic mechanisms open novel classes of regulatory, signaling, and
      organizational choices that can serve as efficient and effective biological
      solutions to problems that are more complex, less robust, or otherwise suboptimal
      to deal with in the context of purely deterministic systems. Research in
      Drosophila melanogaster eye color-vision development and Bacillus subtilis
      competence induction has elegantly traced the role of noise in vital
      physiological processes from fluctuations to phenotypes, and is used here to
      highlight these developments.

PMID- 17179491
TI  - "Beam me up, Scotty!".

PMID- 17179492
TI  - Chronic cough and phlegm in young adults: should we worry?

PMID- 17179494
TI  - When it comes to genes--IPF or NSIP, familial or sporadic--they're all the same.

PMID- 17179493
TI  - Reverse phenotyping in sarcoidosis.

PMID- 17179495
TI  - Tuberculosis fueled by HIV: putting out the flames.

PMID- 17179496
TI  - Notice of duplicate publication.

PMID- 17179497
TI  - Diagnosing empyema in children.

PMID- 17179498
TI  - Interpreting lung functional changes.

PMID- 17179499
TI  - Ventilator-induced lung injury distribution: the key to understanding injury
      mechanisms.

PMID- 17179500
TI  - Appropriate interpretation of lung function and exercise capacity in a
      longitudinal follow-up of preterm children.

PMID- 17179503
TI  - What have we learned from NECOSAD? Practical implications for peritoneal dialysis
      patients.

PMID- 17179504
TI  - Agents that modulate peritoneal membrane structure and function.
AB  - Extensive experience with chronic peritoneal dialysis has identified a series of
      functional and anatomical pathologic changes in the peritoneal membrane thought
      to be the result of repeated insults from bioincompatible solutions. Laboratory
      and clinical findings from recent investigations often conflict and are difficult
      to interpret due to variations in methodologies, animal models, study designs,
      and data analyses. The principal pathophysiologic mechanisms identified thus far
      are oxidative stress, inflammation, and their consequences. Many substances used
      to neutralize the action of these insults, prevent formation of toxic compounds,
      or directly alter solute and water transport to improve peritoneal membrane
      performance have been studied. We herein review the most promising of these
      substances or those that deserve attention because their use has contributed to
      better understanding of peritoneal pathophysiology. Most peritoneal solution
      additives have proved useless due to their toxicity and undesirable effects,
      ineffectiveness, or manufacturing limitations. A few substances deserve more
      attention, particularly those capable of restoring negatively charged membrane
      sites, those that somehow improve permselectivity, scavengers of oxidants, and
      advanced glycation end-product inhibitors and breakers. Recent publications on
      clinical experience with neutral pH, low glucose degradation product (GDP)
      peritoneal solutions, although few and preliminary, are most encouraging. The
      virtual elimination of GDPs in these novel solutions will probably preclude the
      need for GDP scavengers and inhibitors. Nonetheless, there is room for further
      significant improvement in solution biocompatibility and for compounds that may
      restore peritoneal function.

PMID- 17179505
TI  - Musings on guidelines and evidence: a pragmatic and nephrocentric view.

PMID- 17179506
TI  - Musings on guidelines and evidence: an opposing view.

PMID- 17179509
TI  - Impact of nutritional status on peritonitis in CAPD patients.
AB  - OBJECTIVE: To determine the impact of nutritional status on peritonitis in
      patients on continuous ambulatory peritoneal dialysis (CAPD) in a developing
      country. METHODS: 56 patients with end-stage renal disease on CAPD were randomly
      selected for this study. These patients were assessed for nutritional status and
      peritonitis episodes. Nutritional parameters were assessed by anthropometry,
      diet, body mass index (BMI), Nutritional Risk Index (NRI), serum albumin level,
      and Subjective Global Assessment (SGA). Based on SGA, patients were categorized
      into either group 1 (malnutrition, n = 31) or group 2 (normal nutritional status,
      n = 25). Peritonitis was considered the primary outcome and was compared between
      the two groups. RESULTS: Demographic profiles, Kt/V, creatinine clearance, and
      mean follow-up of the two groups were similar. Number of peritonitis episodes was
      significantly higher in patients with malnutrition (25/31) compared to patients
      with normal nutritional status (4/25) (p = 0.001). Mean peritonitis rate per
      patient per year was also significantly higher in patients with malnutrition
      (0.99 +/- 1.07) compared to patients with normal nutritional status (0.18 +/-
      0.42) (p = 0.007). On univariate analysis, malnutrition based on SGA (p = 0.009),
      NRI (p = 0.02), serum albumin level (p = 0.005), and calorie intake (p = 0.006)
      was a significant predictor of peritonitis. On multivariate Cox regression
      analysis, only SGA (p = 0.001, odds ratio 0.08, 95% confidence interval 0.02
      0.36) was found to be a significant predictor of peritonitis. On general linear
      model, the observed power of prediction of peritonitis was 0.96 based on SGA. On
      Kaplan-Meier survival analysis, peritonitis-free survival in patients with normal
      nutrition (42 months) was significantly higher compared to patients with
      malnutrition (21 months) based on SGA (log rank p = 0.003). CONCLUSION: We
      conclude that peritonitis rate is high in patients with malnutrition and that
      malnutrition indices, especially SGA, can predict the peritonitis rate in CAPD
      patients.

PMID- 17179510
TI  - Empirical antibiotic treatment for peritoneal dialysis-related peritonitis: can
      "one size" fit all?

PMID- 17179511
TI  - Ghrelin in chronic kidney disease: too much or too little?

PMID- 17179512
TI  - Ciprofloxacin and cefazolin as a combination for empirical initial therapy of
      peritoneal dialysis-related peritonitis: five-year follow-up.
AB  - The treatment of peritoneal dialysis (PD)-related peritonitis has been a matter
      of extensive investigation, frequently generating therapeutic trials. Several
      combinations of antibiotics have served as newer protocols and tended to be
      efficacious, comfortable, and cost-effective. According to the more recent
      recommendations from the International Society for Peritoneal Dialysis, the
      rationale for empirical initial therapy of clinically detected peritonitis in PD
      patients has been to follow the bacterial profile derived from cultured specimens
      of PD effluents. The current study describes 5 year's experience with the use of
      a new antibiotic regimen for the treatment of peritonitis. We herein analyze the
      outcome of 95 episodes of peritonitis in 54 patients on either automated PD or
      continuous ambulatory PD at the dialysis unit of the Federal University of Rio de
      Janeiro. Peritoneal dialysis-related peritonitis was treated with the combination
      of oral ciprofloxacin and intraperitoneal cefazolin. The observed cure rate was
      85.2% and the sensitivity test was observed to be positive for this combination
      of antibiotics in 88.9% of positive cultures. Of the 14 unsuccessful episodes, 7
      were due to catheter colonization and the rest did not respond to the proposed
      therapy within 48 hours. These 7 cases were also related to peritoneal fluid
      cultures that were resistant to both ciprofloxacin and cefazolin. From this
      study, we propose this combination of oral ciprofloxacin and intraperitoneal
      cefazolin as a first choice for empirical initial therapy of PD-related
      peritonitis, given its efficacy and low cost. However, in order to apply the most
      adequate cost-effective therapy, careful examination of the bacterial profile and
      sensitivities to antibiotics used in each unit is strongly recommended.

PMID- 17179513
TI  - Plasma ghrelin levels in children with chronic renal failure on peritoneal
      dialysis.
AB  - OBJECTIVES: Malnutrition and loss of appetite represent a serious problem in
      children with chronic renal failure. Ghrelin is a newly described hormone
      involved in control of growth hormone secretion, stimulation of food intake, and
      regulation of energy balance. METHODS: Plasma ghrelin levels were compared
      between 12 children on automated peritoneal dialysis (APD) and 9 children on
      conservative treatment of chronic renal failure. Eight healthy children matched
      for age and body mass index (BMI) served as a control group. RESULTS: Plasma
      ghrelin levels were similar in children on APD (698.3 +/- 59.7 pg/mL) and
      children on conservative treatment (675.4 +/- 41.9 pg/mL) compared to healthy
      controls (700.1 +/- 24.7 pg/mL). There was no difference in plasma ghrelin levels
      in children with chronic renal failure regardless of the method of treatment
      (peritoneal dialysis vs conservative treatment). The plasma ghrelin index was
      similar in all three investigated groups: APD 40.2 +/- 8.7 vs conservative
      treatment 39.1 +/- 5.6 vs controls 41.0 +/- 7.8 (pg/mL)/BMI (kg/m2). Plasma
      ghrelin levels did not correlate with age, duration of dialysis treatment,
      height, weight, BMI, creatinine and urea levels, adequacy parameters, or nightly
      glucose load. CONCLUSION: Plasma ghrelin levels in children on APD were not
      different from levels in children on conservative treatment or healthy controls
      with comparable BMI. The persistent state of toxic influence of uremic end
      products could be responsible for such a lack of correlation with
      anthropometrical parameters. Further studies on a larger group of children on APD
      are needed to clarify the effect of ghrelin on nutritional status in children
      with chronic renal failure.

PMID- 17179514
TI  - Predictors of survival and technique success after reinsertion of peritoneal
      dialysis catheter following severe peritonitis.
AB  - BACKGROUND: Peritonitis remains the most important complication of peritoneal
      dialysis (PD). The success rate of restarting PD after severe peritonitis
      (peritonitis unresolved despite treatment with appropriate antibiotics for 3
      days, or fungal or pseudomonas infections) is unclear. We wished to determine PD
      technique survival and overall mortality when PD is offered to these patients and
      to identify predictors of successful reinitiation. METHOD: We conducted a
      retrospective single-center study of 556 patients undergoing PD between January
      2000 and December 2001. We collected demographic information from the 106
      patients who had their PD catheter removed for peritonitis, details about their
      dialysis history and peritonitis, and whether they successfully restarted PD and
      if not, the reason. RESULTS: We divided patients into groups as follows: group 1
      (n = 42) underwent catheter reinsertion, group 2 (n = 16) had no medical
      contraindication to restarting PD but the patients elected to remain on
      hemodialysis, group 3 (n = 35) were deemed medically unsuitable to return to PD,
      and group 4 (n = 13) were those that died within 4 weeks of presenting with
      peritonitis. If there were no medical contraindications, Indo-Asians were more
      likely to retry PD. In group 1, after a mean follow-up of 20 +/- 7.3 months, 23
      of 42 patients restarted PD successfully. Technique survival for group 1 as a
      whole was 69% at 3 months and 55% at the end of follow-up. Patients of greater
      dialysis vintage were more likely to develop PD technique failure after
      restarting. Of those judged suitable for PD, there was no statistically
      significant difference in the mortality of patients who wished to either restart
      PD or remain on hemodialysis (group 1 vs group 2). Significant numbers of
      patients returned successfully to PD after pseudomonas and fungal peritonitis.
      CONCLUSION: Restarting PD after severe peritonitis was possible and safe.
      Ethnicity was an important predictor for wanting to retry PD, but not for
      technique failure: given the choice, Indo-Asians preferred PD and had a higher
      failure rate after restarting, but this did not reach statistical significance.
      Only dialysis vintage predicted technique failure. We conclude that, after severe
      peritonitis, patients should be given the choice to return to PD but risk
      stratification based on dialysis vintage is important. Patient retraining and
      creating a backup arteriovenous fistula might minimize morbidity in these high
      risk patients.

PMID- 17179515
TI  - SEN virus infection in patients on peritoneal dialysis.
AB  - BACKGROUND: Many reports have demonstrated SEN virus (SEN-V) infection rates in
      hemodialysis patients, but the SEN-V infection rate in peritoneal dialysis (PD)
      patients has never been reported. In this study, we determined the prevalence
      rate of SEN-V viremia in a PD population. METHODS: Serum samples from 47 PD
      patients and a control group of 43 subjects from the general population at their
      health examination were assayed for SEN-V-D and -H viremia using polymerase chain
      reaction. RESULTS: The proportions of female gender (p = 0.001), previous
      transfusion (p < 0.0001), and higher mean serum AST level (p = 0.012) were
      significantly higher in PD patients. The prevalence rates of SEN-V-D and/or -H
      viremia were not significantly different between PD patients and controls (27.7%
      vs 32.6%). SEN-V-D(+) patients had lower mean duration of PD than SEN-V(-)
      patients. Mean ALT level was significantly lower in SEN-V-H(+) than in SEN-V(-)
      patients (12.8 +/- 5.8 vs 19.6 +/- 12.1 (IU/L), p = 0.025). None of the SEN-V
      infected PD patients had overt clinical or biochemical signs of liver disease.
      There were no statistically significant differences in prevalence of SEN-V-D
      and/or -H viremia between automated PD (APD) patients and continuous ambulatory
      PD (CAPD) patients. CONCLUSIONS: These results indicate that the SEN-V infection
      rate is not different between healthy individuals and PD patients. Infection with
      SEN-V is not associated with evident liver disease in PD patients and SEN-V
      infection rate is not different between APD patients and CAPD patients.

PMID- 17179516
TI  - Vancomycin disposition following intraperitoneal administration in children
      receiving peritoneal dialysis.
AB  - BACKGROUND: Little information is available on the disposition of vancomycin
      during chronic peritoneal dialysis (PD) in children. The primary objective of
      this study was to investigate the disposition of vancomycin following
      intraperitoneal (IP) administration in children receiving short-dwell [e.g.,
      automated PD (APD)] and long-dwell [e.g., continuous ambulatory PD (CAPD)] PD.
      METHODS: A 6-hour exchange containing vancomycin 500 mg/L, using an exchange
      volume of 1100 mL/m2 body surface area (BSA), was followed by 4-, 6-, and 8-hour
      antibiotic-free exchanges. The 8-hour exchange was followed by three to four 90
      minute antibiotic-free exchanges. Serial blood and dialysis effluent samples were
      obtained and analyzed for vancomycin concentration by high-pressure liquid
      chromatography. Pharmacokinetic parameters were computed using noncompartmental
      methods. RESULTS: The bioavailability of vancomycin during a 6-hour IP exchange
      was 70% +/- 5%, resulting in a delivered dose of 12.0 +/- 1.8 mg/kg, and a 6-hour
      serum vancomycin concentration of 23.3 +/- 7.2 microg/mL. Total body vancomycin
      clearance measured 10.72 +/- 4.52 mL/minute/1.73 m2 BSA, while clearance
      attributable to PD measured 2.78 +/- 1.08 mL/min/1.73 m2 BSA and accounted for
      29% +/- 11% of total vancomycin clearance. Dialysis clearance during long-dwell
      (CAPD) and short-dwell (APD) regimens was similar, measuring 2.46 +/- 1.04 and
      3.09 +/- 1.28 mL/min/1.73 m2 BSA, accounting for 25% +/- 13% and 32% +/- 12% of
      total body clearance respectively. CONCLUSIONS: Intraperitoneal absorption and
      dialysis clearance of vancomycin in children receiving PD are similar to those
      reported in adult dialysis patients. In contrast, total body clearance of
      vancomycin appears to be increased and the elimination half-life decreased in
      children, due to increased elimination by non-renal nondialysis routes. For
      intermittent IP vancomycin therapy in children with peritonitis, an IP load
      containing vancomycin 1000 mg/L (or 30 mg/kg), followed a single full-fill (1100
      mL/m2 BSA) daily exchange, containing vancomycin 250 mg/L (or 7.5 mg/kg), from
      day 2 until the end of treatment will maintain a vancomycin dialysate
      concentration of >4 microg/mL.

PMID- 17179517
TI  - Decreased formation of advanced glycation end-products in peritoneal fluid by
      carnosine and related peptides.
AB  - BACKGROUND: Formation of advanced glycation end-products (AGEs) is a major
      problem in uremic patients treated with peritoneal dialysis (PD). Application of
      additives with known anti-glycosylation properties to PD fluid may be beneficial
      in minimizing the formation of AGEs. This study aimed to evaluate the effect of
      carnosine and its related peptides homocarnosine and anserine against the
      formation of AGEs in PD fluid. METHODS: PD solutions (1.5% dextrose) were
      incubated with human serum albumin (HSA) or collagen (type IV) with or without 10
      mmol/L of each of carnosine, anserine, homocarnosine, histidine, and
      aminoguanidine. The formation of AGEs was followed by fluorescence
      spectrophotometry at weekly intervals for 7 weeks. For the determination of the
      acute effect of carnosine and related compounds, HSA and collagen were incubated
      with 4.25% dextrose PD solutions for 24 hours, followed by incubation with 20
      mmol/L of carnosine and related compounds for another 24 hours. The rate of AGE
      formation was monitored by fluorescence spectrophotometry. RESULTS: Carnosine and
      related compounds showed effective regression in AGE formation in both types of
      proteins in both long- and short-term exposure to PD fluids at a rate of
      effectiveness of the order of carnosine > homocarnosine > anserine,
      aminoguanidine > histidine in long-term exposure, and homocarnosine > carnosine >
      aminoguanidine > anserine > histidine in short-term exposure. CONCLUSION:
      Carnosine and related peptides could suppress the formation of AGEs initiated by
      PD fluid. This observation may provide a new therapeutic approach for the
      prevention and treatment of the AGE-related complications in PD patients.

PMID- 17179518
TI  - Ileal loop strangulation and infarction through a hernia-like opening of local
      adhesive pseudo-membrane after withdrawal from peritoneal dialysis.

PMID- 17179519
TI  - Long-term effect of peritoneal dialysis fluid with neutral pH and low glucose
      degradation product concentration on peritoneum: a case report.

PMID- 17179520
TI  - Analysis of depression and its effect on outcome among adult Indian peritoneal
      dialysis patients.

PMID- 17179521
TI  - Significant intra- and interpatient variation in ultrafiltration achieved by
      icodextrin in APD patients.

PMID- 17179523
TI  - Peritoneal dialysis after orthotopic liver transplant surgery.

PMID- 17179522
TI  - Inflammation and peritoneal dialysis fluids.

PMID- 17179524
TI  - Malnutrition and refeeding syndrome associated with encapsulating peritoneal
      sclerosis.

PMID- 17179525
TI  - Acinetobacter junii causes refractory peritonitis in a patient on automated
      peritoneal dialysis.

PMID- 17179526
TI  - Erythropoietin dose and angiotensin-converting enzyme inhibitors.

PMID- 17179528
TI  - Risk factor research and prevention for anxiety disorders: introduction to the
      special series on risk and prevention of anxiety pathology.
AB  - In relation to treatment-related research in the United States, there is
      relatively little systematic effort focused on the combination of risk and
      prevention for anxiety pathology. This article broadly discusses risk factor
      research and prevention program development for anxiety psychopathology. The
      authors also specifically discuss papers in this special issue that are focused
      on these topics. Risk factor research should be used by clinical researchers to
      inform prevention programs, and reciprocally, prevention knowledge should be
      effectively utilized to drive new, clinically focused risk factor research.

PMID- 17179529
TI  - Pubertal status and emotional reactivity to a voluntary hyperventilation
      challenge predicting panic symptoms and somatic complaints: a laboratory-based
      multi-informant test.
AB  - The main and interactive effects of pubertal status and emotional reactivity to
      bodily sensations elicited by a voluntary hyperventilation challenge were
      examined in relation to panic symptoms and self- and parent-reported somatic
      complaints among 123 (56 females) adolescents between the ages of 12 and 17 years
      (M(age) = 15.05; SD = 1.50). As expected, after controlling for baseline anxiety,
      age, and gender, there was a significant interaction between pubertal status and
      challenge response in predicting the outcome variables. Specifically, adolescents
      reporting more advanced pubertal status and greater reactivity to the challenge
      evidenced greater levels of panic symptoms and somatic complaints, whereas
      pubertal status had relatively less of an effect on these variables among
      adolescents who did not respond as fearfully to the challenge. Results are
      discussed in terms of extant theory and research on anxiety vulnerability among
      adolescents.

PMID- 17179530
TI  - Prediction of "fear" acquisition in healthy control participants in a de novo
      fear-conditioning paradigm.
AB  - Studies using fear-conditioning paradigms have found that anxiety patients are
      more conditionable than individuals without these disorders, but these effects
      have been demonstrated inconsistently. It is unclear whether these findings have
      etiological significance or whether enhanced conditionability is linked only to
      certain anxiety characteristics. To further examine these issues, the authors
      assessed the predictive significance of relevant subsyndromal characteristics in
      72 healthy adults, including measures of worry, avoidance, anxious mood,
      depressed mood, and fears of anxiety symptoms (anxiety sensitivity), as well as
      the dimensions of Neuroticism and Extraversion. Of these variables, the authors
      found that the combination of higher levels of subsyndromal worry and lower
      levels of behavioral avoidance predicted heightened conditionability, raising
      questions about the etiological significance of these variables in the
      acquisition or maintenance of anxiety disorders. In contrast, the authors found
      that anxiety sensitivity was more linked to individual differences in orienting
      response than differences in conditioning per se.

PMID- 17179531
TI  - Prevention and intervention strategies to alleviate preoperative anxiety in
      children: a critical review.
AB  - Preoperative anxiety (anxiety regarding impending surgical experience) in
      children is a common phenomenon that has been associated with a number of
      negative behaviors during the surgery experience (e.g., agitation, crying,
      spontaneous urination, and the need for physical restraint during anesthetic
      induction). Preoperative anxiety has also been associated with the display of a
      number of maladaptive behaviors postsurgery, including postoperative pain,
      sleeping disturbances, parent-child conflict, and separation anxiety. For these
      reasons, researchers have sought out interventions to treat or prevent childhood
      preoperative anxiety and possibly decrease the development of negative behaviors
      postsurgery. Such interventions include sedative premedication, parental presence
      during anesthetic induction, behavioral preparation programs, music therapy, and
      acupuncture. The present article reviews the existing research on the various
      modes of intervention for preoperative anxiety in children. Clinical implications
      and future directions are discussed.

PMID- 17179532
TI  - A critical analysis of approaches to targeted PTSD prevention: current status and
      theoretically derived future directions.
AB  - Although efforts to prevent posttraumatic stress disorder (PTSD) have met with
      relatively limited success, theoretically driven preventive approaches with
      promising efficacy are emerging. The current article critically reviews
      investigations of PTSD prevention programs that target persons at risk for being
      exposed to a traumatic event or who have been exposed to a traumatic event. This
      review uniquely extends prior reviews in this area by using theories of PTSD to
      suggest future directions in the area of PTSD prevention. The authors first
      discuss the primary mechanisms of action believed to account for the failure for
      PTSD symptoms to remit among a substantial minority of traumatic event-exposed
      individuals. Second, empirical progress in PTSD prevention efforts is reviewed.
      Third, the authors consider how existing prevention programs target these
      mechanisms of action. Finally, the authors consider directions for future
      research in the area of targeted PTSD prevention.

PMID- 17179533
TI  - Developmental course(s) of lifetime cigarette use and panic attack comorbidity:
      an equifinal phenomenon?
AB  - The present investigation examined the developmental course(s) of lifetime
      cigarette use and panic attack comorbidity. Participants included 4,409 adults,
      ages 15 to 54 years of age (M(Age) = 33.1, SD = 10.7, N (females) = 2,221) from
      the National Comorbidity Survey (NCS). The primary objective of the present
      investigation was to better understand the developmental course(s) of lifetime
      cigarette use and panic attacks. A second objective of the investigation was to
      evaluate the developmental features of smoking-panic comorbidity in relation to
      other comorbid psychiatric and substance outcomes. Results demonstrated two
      distinct and novel operative developmental patterns of smoking-panic attack co
      occurrence. The theoretical and clinical implications of delineating course
      related factors underlying smoking-panic attack comorbidity are discussed.

PMID- 17179534
TI  - Evaluation in beef cattle of six deoxyribonucleic acid markers developed for
      dairy traits reveals an osteopontin polymorphism associated with postweaning
      growth.
AB  - The objectives of this study were to 1) estimate the allelic frequencies in US
      beef cattle of 6 DNA markers reported to be associated with variation in dairy
      production traits; and 2) evaluate the association of these markers with beef
      production traits. Several genetic markers have been associated with milk yield
      or composition, including polymorphisms in secreted phosphoprotein 1 (SPP1; also
      called osteopontin), growth hormone receptor (GHR), casein S1 (CSN1S1),
      diacylglycerol O-acyltransferase 1 (DGAT1), peroxisome proliferator-activated
      receptor gamma co-activator-1alpha (PPARGC1A), and ATP-binding cassette subfamily
      G (white) member 2 (ABCG2). Allelic frequencies for these 6 markers, and their
      association with 21 phenotypes, were evaluated in 2 crossbred beef cattle
      populations that sample influential industry sires. Five of 6 markers were
      segregating in beef cattle populations; the exception was ABCG2. The SPP1 marker
      was associated with yearling weight (P = 0.025), live weight at slaughter (P =
      0.016), postweaning ADG (P = 0.007), and HCW (P = 0.007) in a large, multisire
      population representing the 7 most populous beef breeds in the United States.
      Postweaning growth trait associations were confirmed in an independent population
      of similar construction, including sires from tropically adapted breeds. The SPP1
      marker was associated with yearling weight (P = 0.034), live weight at slaughter
      (P = 0.011), and postweaning ADG (P = 0.015) and showed a trend toward
      association with HCW (P = 0.083) in this population. Whereas DGAT1, GHR, and
      CSN1S1 polymorphisms showed association with some traits in individual
      populations, the lack of consistent predictive merit between populations
      indicates they may not be suited for beef cattle selection. No significant
      associations were observed for the PPARGC1A marker and any of 21 recorded traits,
      indicating this marker had no apparent value in selection for the beef cattle
      traits tested in these populations. The SPP1 marker had consistent associations
      and effect sizes (10.5 to 11.5 kg of live weight at slaughter) in both
      populations, providing strong evidence for utility of the SPP1 marker for
      postweaning growth in beef cattle.

PMID- 17179535
TI  - Joint analysis of the influence of CYP11B1 and DGAT1 genetic variation on milk
      production, somatic cell score, conformation, reproduction, and productive
      lifespan in German Holstein cattle.
AB  - Recent publications indicate genetic variation in milk production traits on
      proximal BTA14, which cannot be explained solely with genetic variation in the
      DGAT1 gene. To elucidate these QTL effects, animals from a German Holstein
      granddaughter design (18 families, 1,291 sons) were genotyped for CYP11B1 (V30A)
      and DGAT1 (K232A) polymorphisms. Frequencies of alleles of maternal descent were
      estimated for CYP11B1(V) (0.776) and DGAT1(K) (0.549). Allele substitution
      effects (alpha/2) were first calculated for both alleles in separate models and
      then in a joint model. From the joint analysis, CYP11B1(V) effects on fat content
      (+0.04%) and protein content (+0.01%) were positive. Effects on milk yield (-82
      kg), fat yield (-0.5 kg), and protein yield (-1.9 kg) were negative. Compared
      with the individual analysis, DGAT1(K) effects on fat content (+0.28%), protein
      content (+0.06%), and milk yield (-258 kg) were reduced; fat yield (+10.8 kg) was
      enhanced; and protein yield (-3.8 kg) was reduced. In the joint analysis, allele
      substitution effects of CYP11B1(V) and DGAT1(K) together explained more of the
      variation in milk production traits than DGAT1(K) alone. Further significant
      effects were found for CYP11B1(V) and DGAT1(K) among 6 reproduction traits and 14
      conformational traits. These observations indicate a possible negative influence
      of DGAT1(K) on maternal nonreturn rate, and thus, on length of productive life.

PMID- 17179536
TI  - Variance component analysis of quantitative trait loci for pork carcass
      composition and meat quality on SSC4 and SSC11.
AB  - In a previous study, QTL for carcass composition and meat quality were identified
      in a commercial finisher cross. The main objective of the current study was to
      confirm and fine map the QTL on SSC4 and SSC11 by genotyping an increased number
      of individuals and markers and to analyze the data using a combined linkage and
      linkage disequilibrium analysis method. A modified version of the method excludes
      linkage disequilibrium information from the analysis, enabling the comparison of
      results based on linkage information only or results based on combined linkage
      and linkage disequilibrium information. Nine additional paternal half-sib
      families were genotyped for 18 markers, resulting in a total of 1,855 animals
      genotyped for 15 and 13 markers on SSC4 and SSC11, respectively. The QTL
      affecting meat color on SSC4 was confirmed, whereas the QTL affecting LM weight
      could not be confirmed. The combined linkage and linkage disequilibrium analysis
      resulted in the identification of new significant effects for 14 traits on the 2
      chromosomes. Heritabilities of the QTL effects ranged from 1.8 to 13.2%. The
      analysis contributed to a more accurate positioning of QTL and further
      characterized their phenotypic effect. However, results showed that even greater
      marker densities are required to take full advantage of linkage disequilibrium
      information and to identify haplotypes associated with favorable QTL alleles.

PMID- 17179537
TI  - Genetic correlations between performance traits and radiographic findings in the
      limbs of German Warmblood riding horses.
AB  - Results of mare performance tests in the field (MPT-F) of 10,949 mares, mare
      performance tests at station (MPT-S) of 1,712 mares, and inspections of horses
      intended for sale at riding horse auctions (AU) of 4,772 horses were used to
      investigate genetic correlations between corresponding performance traits. Mare
      performance tests were held in 1995 to 2004 and auction inspections in 1999 to
      2004. Scores on a scale from 0 to 10 were given for gaits under rider (walk,
      trot, canter), rideability (evaluated by judging commission and test rider), free
      jumping (ability, style, total), and character. Radiography results of 5,102
      Hanoverian Warmblood horses were used to investigate genetic correlations between
      performance traits and particular radiographic findings. The radiographic
      findings included osseous fragments in fetlock and hock joints, deforming
      arthropathy in hock joints, and distinct radiographic findings in the navicular
      bones, which were analyzed as binary traits, and radiographic appearance of the
      navicular bones, which was analyzed as a quasi-linear trait. Genetic parameters
      were estimated multivariately in linear animal models with REML using information
      on the horses radiographed and their contemporaries (n = 18,609). Heritability of
      performance traits ranged between 0.14 and 0.61, and heritability of radiographic
      findings between 0.14 and 0.33. Additive genetic correlations between
      corresponding performance traits were close to unity for MPT-F and MPT-S, ranged
      from 0.81 to 0.90 for MPT-F and AU, and were 0.75 to 0.92 for MPT-S and AU.
      Genetic correlations between performance and radiography results were mostly
      close to zero. Indications of negative additive genetic correlations were
      observed for deforming arthropathy in hock joints and canter, rideability
      evaluated by test rider, jumping traits and character, and osseous fragments in
      hock joints and character. Selection of horses for radiological health of their
      limbs will assist further genetic improvement of the performance of young Warm
      blood riding horses.

PMID- 17179538
TI  - Genetic parameters for body weight, hip height, and the ratio of weight to hip
      height from random regression analyses of Brahman feedlot cattle.
AB  - The objective of this research was to assess the genetic control of BW, hip
      height, and the ratio of BW to hip height (n = 5,055) in Brahman cattle through
      170 d on feed using covariance function-random regression models. A progeny test
      of Brahman sires (n = 27) generated records of Brahman steers and heifers (n =
      724) over 7 yr. Each year after weaning, calves were assigned to feedlot pens,
      where they were fed a high-concentrate grain diet. Body weights and hip heights
      were recorded every 28 d until cattle reached a targeted fatness level. All
      calves had records through 170 d on feed; subsequent records were excluded.
      Models included contemporary group (sex-pen-year combinations, n = 63) and age at
      the beginning of the feeding period as a covariate. The residual error structure
      was modeled as a random effect, with 2 levels corresponding to two 85-d periods
      on feed. Information criterion values indicated that linear, random regression
      coefficients on Legendre polynomials of days on feed were most appropriate to
      model additive genetic effects for all 3 traits. Cubic (hip height and BW:hip
      height ratio) or quartic (BW) polynomials best modeled permanent environmental
      effects. Estimates of heritability across the 170-d feeding period ranged from
      0.31 to 0.53 for BW, from 0.37 to 0.53 for hip height, and from 0.23 to 0.6 for
      BW:hip height ratio. Estimates of the permanent environmental proportion of
      phenotypic variance ranged from 0.44 to 0.58 for BW, 0.07 to 0.26 for hip height,
      and 0.30 to 0.48 for BW:hip height ratio. Within-trait estimates of genetic
      correlation on pairs of days on feed (at 28-d intervals) indicated lower
      associations of BW:hip height ratio EBV early and late in the feeding period but
      large positive associations for BW or hip height EBV throughout. Estimates of
      genetic correlations among the 3 traits indicated almost no association of BW:hip
      height ratio and hip height EBV. The ratio of BW to hip height in cattle has
      previously been used as an objective measure of BCS in cows or calves; it may
      offer a unique assessment of body dimension. Results indicated that there is
      substantial additive genetic variation for this trait, and it may be possible to
      use EBV to increase BW without increasing frame score in Brahman cattle.

PMID- 17179539
TI  - Genetic parameters for reproduction and production traits of Landrace sows in
      Thailand.
AB  - Data from Thai Landrace sows were used to estimate genetic parameters for
      reproduction and production traits in first and later parities. The reproduction
      traits investigated were total number of piglets born per litter (TB), number of
      stillborn piglets (SB), and number of piglets born alive but dead within 24 h
      (BAD). The reproduction data pertained to 12,603 litters born between 1993 and
      2005. The production measures were ADG and backfat thickness (BF); these were
      recorded in 4,163 boars and 15,171 gilts. Analyses were carried out with a
      multivariate animal model using average information REML procedures. Heritability
      estimates of reproduction traits for first parity were 0.03 +/- 0.02 for TB, 0.04
      +/- 0.02 for SB, and 0.06 +/- 0.02 for BAD. For later parities, they were 0.07 +/
      0.01 for TB, 0.03 +/- 0.04 for SB, and 0.02 +/- 0.01 for BAD. Heritability
      estimates for production traits were 0.38 +/- 0.02 for ADG and 0.61 +/- 0.02 for
      BF. Genetic correlations between ADG and TB tended to be favorable, and genetic
      correlations between BF and TB tended to be unfavorable in all parities. However,
      BF was genetically correlated unfavorably with SB in later parities, and the
      genetic correlations between TB and BAD tended to be unfavorable in all parities.
      The genetic correlations of TB, SB, and BAD between first and later parities were
      0.85 +/- 0.13, 0.79 +/- 0.16, and 0.71 +/- 0.24, respectively. Selection for high
      growth rate will probably increase TB, and selection for low BF will decrease TB
      and increase SB. The results obtained also indicated that BAD will increase if
      there is selection pressure for high TB.

PMID- 17179540
TI  - Genetic (co)variance components for ewe productivity traits in Katahdin sheep.
AB  - The objective of this study was to estimate genetic parameters, in Katahdin
      sheep, for total weight of litter weaned per ewe lambing (TW) and its components,
      number of lambs born (NB), number of lambs weaned (NW), and average weight of
      lambs weaned (AW) measured as traits of the ewe. Weaning weights of lambs (WW)
      were adjusted to 60 d of age and for effects of ewe age, lamb sex, and type of
      birth and rearing and averaged over all lambs in the litter to obtain AW. The 60
      d age-adjusted WW were adjusted for ewe age and lamb sex and summed over all
      lambs in the litter to obtain TW. A total of 2,995 NB and NW records, 2,622 AW,
      and 2,714 TW records were available from 1,549 ewes (progeny of 235 sires) over 4
      yr. Heritabilities were initially estimated for each trait from univariate REML
      analyses. Estimates of genetic correlations were obtained from bi- and trivariate
      analyses. Models for NB, NW, AW, and TW included random ewe additive and
      permanent environmental effects. A random service sire effect was also fit for AW
      and TW. Heritabilities of TW, NB, NW, and AW from univariate analyses were 0.12,
      0.12, 0.09, and 0.13 (all P < 0.01), respectively. Permanent environmental
      effects were significant (P < 0.01) for TW and AW. Genetic correlations of TW
      with NB, NW, and AW ranged from 0.27 to 0.33, 0.88 to 0.91, and 0.72 to 0.76,
      respectively; those of NB with NW and AW ranged from 0.70 to 0.75 and -0.01 to
      0.02, respectively; and that between NW and AW ranged from 0.40 to 0.55. Genetic
      parameters were also obtained for lamb survival to weaning (LS) and WW measured
      as traits of the lamb, and the relationships between WW of the ewe as a lamb and
      her subsequent records for NB and NW were also estimated. A total of 5,107 LS and
      5,444 WW records were available. Models for WW and LS included random animal and
      maternal genetic, maternal permanent environmental, and litter effects.
      Heritability of WW ranged from 0.15 to 0.20. There was no evidence of genetic
      effects on LS. Direct genetic correlations of WW with NB and NW were not
      significantly different from zero. The correlation between maternal genetic
      effects on WW, and animal genetic effects on NW, averaged 0.35. Results of this
      study indicate that there are no major antagonisms among TW and its components,
      so that selection for TW would not have adverse effects on any component traits
      and vice versa. Maternally superior ewes for WW appear to also be somewhat
      superior for NW.

PMID- 17179541
TI  - Genetic relationships among calving ease, calving interval, birth weight, and
      weaning weight in the Asturiana de los Valles beef cattle breed.
AB  - The aim of this paper was to estimate direct and maternal genetic parameters for
      calving ease (CE), birth weight (BrW), weaning weight (WW), and calving interval
      (CI) to assess the possibility of including this information in beef cattle
      improvement programs. Field data, including a total of 59,813 animals (1,390
      sires and 1,147 maternal grand sires) from the Asturiana de los Valles beef
      cattle breed, were analyzed with a multivariate linear model. Estimates of
      heritability for direct genetic effects (CED, CID, BrWD, and WWD) were 0.191 +/-
      0.019, 0.121 +/- 0.013, 0.390 +/- 0.030, and 0.453 +/- 0.035, respectively,
      whereas those for maternal genetic effects (CEM, BrWM, and WWM) were 0.140 +/-
      0.015, 0.208 +/- 0.020, and 0.138 +/- 0.022, respectively. Genetic correlations
      between direct or maternal genetic effects across traits were, in general,
      positive and moderate to low. However, genetic correlation for the pair CED-BrWD
      was positive and high (0.604 +/- 0.064). Genetic correlations between the direct
      and maternal genetic effects within a trait were negative and moderate (-0.219 +/
      0.097 for CE, -0.337 +/- 0.080 for BrW, and -0.440 +/- 0.102 for WW). Genetic
      correlations for CED-BrWM and CED-WWM were -0.121 +/- 0.090 and -0.097 +/- 0.113,
      respectively. The genetic correlation for CEM-CID was unfavorable (0.485 +/-
      0.078), and those for CEM-BrWD (-0.094 +/- 0.079) and CEM-WWD (-0.125 +/- 0.082)
      were low and negative. The genetic correlation between CID and WWM was favorable
      (-0.148 +/- 0.106). Overall, the data presented here support the hypothesis that
      maternal effects for CE and BrW are not the same and that the genetic
      relationships between CI and maternal effects for WW in beef cattle follow a
      similar pattern to that reported between CI and milk yield in dairy cattle.
      Moreover, the need to include direct and maternal breeding values in beef cattle
      selection programs is suggested.

PMID- 17179542
TI  - A longitudinal study on growth and growth variables in dogs of four large breeds
      raised in domestic environments.
AB  - The main objective of this study was to describe the growth patterns of 4 large
      dog breeds [Newfoundland (NF), Labrador retriever (LR), Leonberger (LEO), and
      Irish wolfhound (IW)] raised in domestic environments and concomitant changes in
      2 growth-related clinical variables: total serum alkaline phosphatase (ALP) and
      the circumference of the distal radius and ulna (CDRU). The second objective was
      to investigate whether these measurements were affected by a range of independent
      variables like age, sex, litter number, and birth weight. Seven hundred dogs were
      included in the study, and BW data, separated by breed and sex, were fitted to
      the Gompertz function. Birth weight, adjusted for litter number, differed
      significantly between sexes for 3 breeds (LEO, P = 0.004; NF, P = 0.02; LR, P =
      0.009) and approached significance for IW (P = 0.07). Estimated mean BW increased
      rapidly during the first 100 d after birth in all 4 breeds, then plateaued, with
      maturity being reached between 351 (female LR) and 413 d (male NF). Estimated
      mature BW ranged from 30.8 kg for the female LR up to 65.7 kg for the male IW.
      Weight gain, as expressed by the derivative of the Gompertz function, reached its
      peak in the smallest breed (LR) at the youngest age, 89 d for the females and 95
      d for males. Log-transformed BW was significantly related to age, breed, and sex,
      and the age x sex and age x breed interactions. Within breeds, age, birth weight,
      and litter number had a significant effect on log-transformed BW. The estimated
      average CDRU increased from 90 d of age toward a peak at 180 d. Thereafter, CDRU
      declined and stabilized at about 1 yr of age. The estimated total ALP
      concentrations decreased from 90 to 360 d of age, after which they stabilized, at
      mean concentrations varying among breeds from 98 to 131 IU/L. Maximum least
      squares mean total ALP concentrations were found at 3 mo of age in all breeds,
      with the greatest least squares mean concentration in the IW breed (713 IU/L). In
      a mixed model analysis of the complete data set, total ALP was affected (P <
      0.001) by age, breed, and the interaction of age x breed. This study described
      the main factors influencing growth and provided reference data for other
      studies, including those related to nutrition and disorders of growth.

PMID- 17179543
TI  - Modeling the growth of the Goettingen minipig.
AB  - The Goettingen minipig developed at the University of Goettingen, Germany, is a
      special breed for medical research. As a laboratory animal it has to be as small
      and light as possible to facilitate handling during experiments. For achieving
      the breeding goal of small body size in the future, the growth pattern of the
      minipig was studied. This study deals with the analysis of minipig BW by modeling
      growth with linear and nonlinear functions and comparing the growth of the
      minipigs with that of normal, fattening pigs. Data were provided by Ellegaard
      Goettingen minipigs, Denmark, where 2 subpopulations of the Goettingen basis
      population are housed. In total 189,725 BW recordings of 33,704 animals collected
      from birth (d 0) to 700 d of age were analyzed. Seven nonlinear growth functions
      and 4 polynomial functions were applied. The growth models were compared by using
      the Akaike's information criterion (AIC). Regarding the whole growth curve,
      linear polynomials of third and fourth order of fit had the smallest AIC values,
      indicating the best fit for the minipig BW data. Among the nonlinear functions,
      the logistic model had the greatest AIC value. A comparison with fattening pigs
      showed that the minipigs have a nearly linear BW development in the time period
      from birth to 160 d. Fattening pigs have very low weight gains in their first 7
      wk in relation to a specific end weight. After 7 wk, fattening pigs have
      increased growth, resulting in a growth curve that is more sigmoid than the
      growth curve of the minipig. Based on these results, further studies can be
      conducted to analyze the growth with random regression models and to estimate
      variance components for optimizing the strategies in minipig breeding.

PMID- 17179544
TI  - Immune responses of piglets to weaning stress: impacts of photoperiod.
AB  - An acute stress response can be provoked by abrupt social, nutritional, and
      environmental changes associated with weaning, and this may disrupt homeostasis
      and thus compromise well-being. Manipulating environmental factors, such as
      photoperiod, might provide a simple way to reduce the physiological consequences
      that piglets experience due to weaning stress. The objective of this study was to
      evaluate the impacts of photoperiod manipulation across various weaning ages on
      leukocyte populations, lymphocyte proliferation, natural killer cytotoxicity
      (NK), chemotaxis, phagocytosis, and immunoglobulin G, cortisol, and BW of piglets
      during the nursery phase. Sixty-eight crossbred piglets were obtained from sows
      kept on a short-day (8 h of light/d) photoperiod from d 90 of gestation until
      weaning. Piglets were weaned at 14, 21, or 28 d of age and kept on a short or
      long (16 h of light/d) photoperiod until 10 wk of age. Piglet BW and blood
      samples were collected at weaning and at 6, 8, and 10 wk of age. Pigs weaned at
      28 d had reduced neutrophil counts (P < 0.001), phagocytosis (P < 0.001), and
      lymphocyte proliferation (P < 0.05) at weaning compared with those weaned at 14
      and 21 d. Pigs weaned at 21 d tended to have lower (P = 0.08) lymphocyte counts
      than did pigs weaned at 14 or 28 d. Pigs weaned at 14 d had reduced (P < 0.01) NK
      relative to those weaned at 21 or 28 d. Photoperiod also influenced pig BW and
      immune status. Generally, those pigs on the long-day photoperiod and weaned at 28
      d were heavier (P < 0.001) than their counterparts weaned at 14 or 21 d. At 6 wk
      of age, NK was greater (P = 0.002) in pigs kept on a long day and weaned at 14 or
      21 d than in pigs weaned at 28 d. Phagocytosis was less (P = 0.005) at 6 wk of
      age, but was greater at 8 wk, in piglets kept on the long day and weaned at 28 d
      than in long-day pigs weaned at 14 or 21 d. These results suggest that
      photoperiod differentially influences immune responses in piglets weaned at
      different ages and indicate an inverse relationship between growth and immune
      status. Here, weaning at 28 d and a long-day photoperiod was the treatment
      combination that was most physiologically beneficial to piglets, whereas a 14-d
      weaning and short-day photoperiod was least physiologically beneficial.

PMID- 17179545
TI  - Insulin sensitivity during pregnancy, lactation, and postweaning in primiparous
      gilts.
AB  - The objectives were to examine changes in the insulin response during pregnancy,
      lactation, and postweaning in an experiment involving 10 primiparous Landrace x
      Large White gilts. Gilts were catheterized at 50 d of pregnancy, and tests were
      conducted at approximately 59 d of pregnancy (midpregnancy; MP), 106 d of
      pregnancy (end of pregnancy; EP), 17 d of lactation (L), and 9 d after weaning
      (PW), respectively. Changes in plasma glucose, insulin, and NEFA concentrations
      were studied after 3 different tests: ingestion of 1.3 kg of feed (meal test); a
      glucose tolerance test; and 2 euglycemic, hyperinsulinemic clamp tests, in which
      20 and 55 ng of insulin x kg of BW(-1) x min(-1) were infused during 150 min.
      Fasting concentrations of plasma glucose were less during L than during the other
      stages (P < 0.001). Concentrations of glucose and insulin increased after
      ingestion of the meal and decreased thereafter. Plasma insulin returned to basal
      concentrations at all stages, whereas glucose reached basal concentrations before
      the end of the meal at the PW test only. Postprandial concentrations of plasma
      glucose and area under the curve for insulin were greater during L than at the
      other stages (P < 0.05); both tended to be greater during EP than during MP or
      after weaning. Concentrations of NEFA were greater during L than at other stages
      before as well as after a meal (P < 0.001). Glucose half-life was greatest during
      L, least during MP and PW, and intermediate during EP. Compared with other
      stages, insulin secretion during the tolerance tests seemed to be delayed during
      L and, to a lesser extent, at EP. Irrespective of insulin dose, glucose infusion
      rates during the clamps did not differ between MP and PW, and were greater than
      during EP and L (P < 0.001). Plasma concentrations of NEFA decreased less rapidly
      during L than during the other stages. Gilts from EP developed a state of insulin
      resistance that was further accentuated during L. Changes in insulin
      responsiveness at MP, EP, and L may be an adaptation that allows gilts to
      acclimate to the increasing demand of glucose by the growing conceptus and the
      even greater demands of lactation.

PMID- 17179546
TI  - Long-term feed intake regulation in sheep is mediated by opioid receptors.
AB  - These experiments were conducted to determine if 1) syndyphalin-33 (SD33), a mu
      opioid receptor ligand, affects feed intake; 2) SD33 effects on feed intake are
      mediated by actions on opioid receptors; and 3) its activity can counteract the
      reduction in feed intake associated with administration of bacterial endotoxin.
      In Exp. 1, 5 mixed-breed, castrate male sheep were housed indoors in individual
      pens. Animals had ad libitum access to water and concentrate feed. Saline (SAL;
      0.9% NaCl) or SD33 (0.05 or 0.1 micromol/kg of BW) was injected i.v., and feed
      intake was determined at 2, 4, 6, 8, 24, and 48 h after the i.v. injections. Both
      doses of SD33 increased (at least P < 0.01) feed intake at 48 h relative to
      saline. In Exp. 2, SAL + SAL, SAL + SD33 (0.1 micromol/kg of BW), naloxone (NAL;
      1 mg/kg of BW) + SAL, and NAL + SD33 were injected i.v. Food intake was
      determined as in Exp. 1. The SAL + SD33 treatment increased (P = 0.022) feed
      intake at 48 h relative to SAL + SAL. The NAL + SAL treatment reduced (at least P
      < 0.01) feed intake at 4, 6, 8, 24, and 48 h, whereas the combination of NAL and
      SD33 did not reduce feed intake at 24 (P = 0.969) or 48 h (P = 0.076) relative to
      the saline-treated sheep. In Exp. 3, sheep received 1 of 4 treatments: SAL + SAL,
      SAL + 0.1 micromol of SD33/kg of BW, 0.1 microg of lipopolysaccharide (LPS)/kg of
      BW + SAL, or LPS + SD33, and feed intake was monitored as in Exp. 1.
      Lipopolysaccharide suppressed cumulative feed intake for 48 h (P < 0.01) relative
      to saline control, but SD33 failed to reverse the reduction in feed intake during
      this period. These data indicate that SD33 increases feed intake in sheep after
      i.v. injection, and its effects are mediated via opioid receptors. However, the
      LPS-induced suppression in feed intake cannot be overcome by the opioid receptor
      ligand, SD33.

PMID- 17179547
TI  - Influence of litter size on metabolic status and reproductive axis in primiparous
      sows.
AB  - This study on primiparous sows was designed to 1) determine the impact of nursing
      a large litter on LH secretion and follicular development, and 2) investigate the
      metabolic adaptations by which milk yield increases with litter size. At
      farrowing, crossbred, primiparous sows were assigned to 1 of 3 experimental
      groups differing in litter size and feed allowance. Sows with 13 or 14 piglets
      (13AL, n = 7) were fed ad libitum. Sows with 7 piglets were fed ad libitum (7AL,
      n = 6) or were feed-restricted (7R, n = 8). The restriction was based on the
      estimated energy deficiency for the 13AL sows. On d 9 +/- 1 of lactation, a
      jugular catheter was surgically implanted. Serial blood samplings and glucose
      tolerance tests were performed in mid- and late lactation. Sows were slaughtered
      3 d after weaning, and ovarian characteristics were recorded. During lactation,
      the 7AL sows lost no or little body reserves, and their estimated energy balance
      was near zero. The 13AL and 7R sows exhibited similar negative energy balances
      and similar losses of backfat and estimated lipid content. Litter growth rate was
      greater (P < 0.05) in the 13AL than in the 7AL and 7R groups. After weaning, the
      volume of the largest 14 follicles was smaller (P < 0.05) in sows nursing 13 or
      14 piglets than in sows with 7 piglets. Plasma concentrations of LH and LH pulse
      frequency did not differ between groups (P > 0.1). The longer glucose half-life
      on d 16 than on d 27 of lactation (22.5 vs. 18.8 min; P < 0.05) indicated a lower
      glucose tolerance in mid- than in late lactation. The area under the insulin
      curve was greater in the 7AL than in the 13AL sows (P = 0.08) and intermediate in
      the 7R group, with no differences in glucose profiles. This led to the suggestion
      that the 7AL sows were more resistant to insulin than the 13AL sows. In all
      groups of sows, follicular development after weaning was correlated with LH
      secretion in midlactation. Active follicular development was associated with
      prolonged secretion of insulin in response to glucose challenge. Our results show
      that besides litter size, a sow's metabolic status in lactation influences
      follicular maturation after weaning and also indicate that the metabolic
      adaptations by which primiparous sows nursing large litters increase litter
      growth rate and body reserve mobilization do not involve an accentuated
      peripheral insulin resistance.

PMID- 17179548
TI  - Luteinizing hormone release after administration of the gonadotropin-releasing
      hormone agonist Fertilan (goserelin) for synchronization of ovulation in pigs.
AB  - The generic GnRH agonist, Fertilan (goserelin), was tested for the ability to
      induce an LH surge and ovulation in estrus-synchronized gilts. Three experiments
      were performed to 1) examine the effect of various doses of Fertilan on secretion
      of LH in barrows, to select doses to investigate in gilts (Exp. 1); 2) determine
      doses of Fertilan that would induce a preovulatory-like rise of LH in gilts (Exp.
      2); and 3) determine the time of ovulation after Fertilan treatment (Exp. 3). In
      Exp. 1, 10 barrows were injected on d 1, 4, 7, 10, and 13 with 10, 20, or 40
      microg of Fertilan; 50 microg of Gonavet (depherelin; GnRH control) or saline
      (negative control); and sequential blood samples were collected for 480 min.
      There was a dose-dependent stimulation (P < 0.05) of LH release. Maximal plasma
      concentrations of LH (LH(MAX)) were 2.1 +/- 0.2, 4.1 +/- 0.3, 2.6 +/- 0.4, and
      3.4 +/- 0.3 ng/mL after 10, 20, and 40 microg of Fertilan and 50 microg of
      Gonavet, respectively, and duration of release was 78 +/- 9, 177 +/- 12, 138 +/-
      7, and 180 +/- 11 min, respectively. Fertilan doses of 10 and 20 microg were
      deemed to be the most suitable for testing in gilts. In Exp. 2, 12 gilts received
      (after estrus synchronization with Regumate and eCG) injections of 10 or 20
      microg of Fertilan or 50 microg of Gonavet 80 h after eCG to stimulate a
      preovulatory-like LH surge and ovulation. An LH surge was induced in 3 of the 4
      gilts in both of the Fertilan groups and in all of the Gonavet-treated gilts.
      Characteristics of induced release of LH did not differ among groups: LH(MAX),
      5.0 +/- 0.9 vs. 4.6 +/- 1.8 vs. 6.6 +/- 1.1 ng/mL; duration, 11.7 +/- 2.0 vs.
      12.3 +/- 2.2 vs. 14.3 +/- 0.5 h; interval from GnRH injection to LH(MAX), 4.0 +/-
      2.0 vs. 6.7 +/- 1.3 vs. 5.8 +/- 1.6 h. In Exp. 3, estrus-synchronized gilts were
      injected with 20 microg of Fertilan (n = 8) or 50 microg of Gonavet (n = 4), and
      the time of ovulation was determined by repeated endoscopic examination. Time of
      ovulation ranged from 34 to 42 h postGnRH; however, ovulation occurred earlier in
      the Gonavet compared with the other groups (P < 0.05). Results of these
      experiments indicate that 1) barrows are an appropriate model for determining
      GnRH doses that can be effective in inducing a preovulatory-like LH surge in
      females; 2) the generic GnRH agonist Fertilan, at doses of 10 to 20 microg, can
      stimulate an LH surge in gilts, with subsequent ovulation; and 3) Fertilan at
      doses of 10 and 20 microg should be examined further for use in fixed-time
      insemination protocols.

PMID- 17179549
TI  - Rescuing valuable genomes by animal cloning: a case for natural disease
      resistance in cattle.
AB  - Tissue banking and animal cloning represent a powerful tool for conserving and
      regenerating valuable animal genomes. Here we report an example involving cattle
      and the rescue of a genome affording natural disease resistance. During the
      course of a 2-decade study involving the phenotypic and genotypic analysis for
      the functional and genetic basis of natural disease resistance against bovine
      brucellosis, a foundation sire was identified and confirmed to be genetically
      resistant to Brucella abortus. This unique animal was utilized extensively in
      numerous animal breeding studies to further characterize the genetic basis for
      natural disease resistance. The bull died in 1996 of natural causes, and no semen
      was available for AI, resulting in the loss of this valuable genome. Fibroblast
      cell lines had been established in 1985, cryopreserved, and stored in liquid
      nitrogen for future genetic analysis. Therefore, we decided to utilize these
      cells for somatic cell nuclear transfer to attempt the production of a cloned
      bull and salvage this valuable genotype. Embryos were produced by somatic cell
      nuclear transfer and transferred to 20 recipient cows, 10 of which became
      pregnant as determined by ultrasound at d 40 of gestation. One calf survived to
      term. At present, the cloned bull is 4.5 yr old and appears completely normal as
      determined by physical examination and blood chemistry. Furthermore, in vitro
      assays performed to date indicate this bull is naturally resistant to B. abortus,
      Mycobacterium bovis, and Salmonella typhimurium, as was the original genetic
      donor.

PMID- 17179550
TI  - Growth factor messenger ribonucleic acid expression during differentiation of
      porcine embryonic myogenic cells.
AB  - The growth factors, IGF-I and II, their binding proteins, IGFBP, and members of
      the transforming growth factor (TGF) superfamily (myostatin and TGFbeta1) are
      known to regulate proliferation and differentiation of myogenic cells. We
      hypothesized that changes in the relative expression of members of the IGF and
      TGFbeta systems play a significant role in regulating myogenesis in porcine
      embryonic myogenic cell (PEMC) cultures. Therefore, determining the expression
      patterns of these factors during PEMC myogenesis is important. Consequently, we
      used real-time PCR to explore the pattern of IGF-I; IGF-II; IGFBP-2, -3, and -5;
      IGF-type-I receptor; myogenin; myostatin; and TGFbeta1 mRNA expression during
      PEMC myogenesis. The progression of differentiation was assessed using creatine
      kinase activity and myogenin mRNA expression. As anticipated, creatine kinase
      activity was low in PEMC cultures at 48 h and increased 20-fold (P < 0.0001)
      between 48 h and its peak at 144 h. Similarly, myogenin mRNA was low at 48 h and
      increased approximately 5-fold (P < 0.0001) as differentiation progressed,
      peaking at 120 h and decreasing at 144 h. The patterns of IGF-I and IGFBP-2 mRNA
      expression were similar and were relatively lower in 48-h PEMC cultures,
      increasing approximately 5-fold (P < 0.0001) to their greatest levels at 120 h.
      In contrast, IGF-II and IGFBP-5 mRNA levels were relatively high at 48 h, peaking
      at 72 h, and steadily decreasing by 60 and 80%, respectively (P < 0.001), at 144
      h. The level of IGF-type-I receptor mRNA was relatively high until 96 h of
      culture, after which it decreased 40% (P < 0.01), reaching a low at 144 h. Levels
      of IGFBP-3 mRNA were relatively high at 48 h, dropped approximately 40% to their
      lowest level at 72 h (P < 0.001), and then increased approximately 60% (P <
      0.001) to their greatest levels at 144 h. Levels of TGFbeta1 mRNA decreased
      approximately 30% (P < 0.0001) between 48 and 96 h, then quickly rebounded to a
      peak at 120 h, and by 144 h had dropped to the levels seen at 72 h. Myostatin
      mRNA was at its greatest level at 48 h and declined rapidly between 72 and 96 h,
      finally decreasing by approximately 80% at 144 h (P < 0.0001). Our data
      demonstrate that these factors are differentially regulated during PEMC
      myogenesis and provide new information about their pattern of mRNA expression in
      cultured porcine muscle cells.

PMID- 17179551
TI  - Ovarian, hormonal, and reproductive events associated with synchronization of
      ovulation and timed appointment breeding of Bos indicus-influenced cattle using
      intravaginal progesterone, gonadotropin-releasing hormone, and prostaglandin
      F2alpha.
AB  - The objectives of this study were to 1) compare cumulative pregnancy rates in a
      traditional management (TM) scheme with those using a synchronization of
      ovulation protocol (CO-Synch + CIDR) for timed AI (TAI) in Bos indicus-influenced
      cattle; 2) evaluate ovarian and hormonal events associated with CO-Synch + CIDR
      and CO-Synch without CIDR; and 3) determine estrual and ovulatory distributions
      in cattle synchronized with Select-Synch + CIDR. The CO-Synch + CIDR regimen
      included insertion of a controlled internal drug-releasing device (CIDR) and an
      injection of GnRH (GnRH-1) on d 0, removal of the CIDR and injection of PGF2alpha
      (PGF) on d 7, and injection of GnRH (GnRH-2) and TAI 48 h later. For Exp. 1,
      predominantly Brahman x Hereford (F1) and Brangus females (n = 335) were
      stratified by BCS, parity, and day postpartum (parous females) before random
      assignment to CO-Synch + CIDR or TM. To maximize the number of observations
      related to TAI conception rate (n = 266), an additional 96 females in which TM
      controls were not available for comparison also received CO-Synch + CIDR.
      Conception rates to TAI averaged 39 +/- 3% and were not affected by location,
      year, parity, AI sire, or AI technician. Cumulative pregnancy rates were greater
      (P < 0.05) at 30 and 60 d of the breeding season in CO-Synch + CIDR (74.1 and
      95.9%) compared with TM (61.8 and 89.7%). In Exp. 2, postpartum Brahman x
      Hereford (F1) cows (n = 100) were stratified as in Exp. 1 and divided into 4
      replicates of 25. Within each replicate, approximately one-half (12 to 13)
      received CO-Synch + CIDR, and the other half received CO-Synch only (no CIDR). No
      differences were observed between treatments, and the data were pooled.
      Percentages of cows ovulating to GnRH-1, developing a synchronized follicular
      wave, exhibiting luteal regression to PGF, and ovulating to GnRH-2 were 40 +/- 5,
      60 +/- 5, 93 +/- 2, and 72 +/- 4%, respectively. In Exp. 3, primiparous Brahman x
      Hereford, (F1) heifers (n = 32) and pluriparous cows (n = 18) received the Select
      Synch + CIDR synchronization regimen (no GnRH-2 or TAI). Mean intervals from CIDR
      removal to estrus and ovulation, and from estrus to ovulation were 70 +/- 2.9, 99
      +/- 2.8, and 29 +/- 2.2 h, respectively. These results indicate that the
      relatively low TAI conception rate observed with CO-Synch + CIDR in these studies
      was attributable primarily to failure of 40% of the cattle to develop a
      synchronized follicular wave after GnRH-1 and also to inappropriate timing of
      TAI/GnRH-2.

PMID- 17179552
TI  - Effect of exercise, training, circadian rhythm, age, and sex on insulin-like
      growth factor-1 in the horse.
AB  - Insulin-like growth factor-1 could be a useful marker in the horse for
      diagnostic, selection, or forensic purposes, provided its physiological
      regulation is well understood. The objective of this study was to investigate
      factors, such as acute exercise, fitness training, time of day, sex, and age,
      that may influence serum IGF-1 in normal, healthy horses. Throughout a 9-wk
      training program, 6 geldings maintained a mean (+/- SEM) IGF-1 concentration of
      302 +/- 29 ng/mL. Moderate or high intensity exercise had no effect on IGF-1
      concentrations, when pre- and postexercise values were compared. Over a 24-h
      period, there was some variation in IGF-1 concentrations but no clear diurnal
      rhythm. Concentrations of IGF-1 were measured in a large population of
      thoroughbred horses (1,880) on 3 continents. The population deviated slightly
      from a normal distribution (P < 0.001) because of large IGF-1 concentrations in
      10 horses. The global mean IGF-1 concentration was 310 +/- 2.2 ng/mL, with a
      greater mean value (P < 0.001) in gonad-intact males (336 +/- 5.6 ng/mL) than in
      females (303 +/- 3.2 ng/mL) or geldings (302 +/- 3.2 ng/mL). However, the
      greatest IGF-1 concentrations observed for all stallions, mares, and geldings
      were 627, 676, and 709 ng/mL, respectively. In mares and geldings, IGF-1
      concentrations showed a gradual decrease with advancing age (P < 0.001), but the
      effect was much less marked in stallions. This study confirms that IGF-1
      concentrations are stable, compared with GH concentrations, in the horse and that
      a meaningful measure of IGF-1 status can be obtained from a daily serum sample.

PMID- 17179553
TI  - Invited review: Amino acid bioavailability and digestibility in pig feed
      ingredients: terminology and application.
AB  - In this review, the terminology that is used to describe the bioavailability and
      ileal digestibility of AA in pig feed ingredients is defined. Aspects of the
      methodology to establish bioavailability and ileal digestibility values also are
      discussed, and recommendations about the use of these values are provided. Two
      main factors can contribute to differences between bioavailability and ileal
      digestibility of AA. First, some AA, such as Lys, may be absorbed in chemical
      complexes that preclude their use for metabolism. Second, fermentation in the
      upper gut may result in a net loss or gain of AA to the animal. In addition,
      dietary effects on the efficiency of using bioavailable AA intake for tissue
      growth or milk production should be considered and may be attributed to
      endogenous AA losses in the hindgut and the metabolic costs associated with
      endogenous gut protein synthesis and losses. Ileal digestibility values may be
      expressed as apparent ileal digestibility (AID), standardized ileal digestibility
      (SID), or true ileal digestibility (TID). These terms are used to specify how
      ileal endogenous AA losses are reflected in digestibility values. Ileal
      endogenous AA losses may be separated into basal losses, which are not influenced
      by feed ingredient composition, and specific losses, which are induced by feed
      ingredient characteristics such as levels and types of fiber and antinutritional
      factors. Values for AID are established when total ileal outflow of AA (i.e., the
      sum of endogenous losses and nondigested dietary AA) is related to dietary AA
      intake. A concern with the use of AID values is that these are not additive in
      mixtures of feed ingredients. This concern may be overcome by correcting AID
      values for defined basal endogenous losses of AA, which yields SID values.
      Furthermore, if the AID values are corrected for basal and specific endogenous
      losses, then values for TID are calculated. However, reliable procedures to
      routinely measure specific endogenous losses are not yet available. It is
      recommended that basal ileal endogenous losses of AA should be measured in
      digestibility experiments using a defined protein-free diet and that these losses
      are reported with observed AID and SID values. It is suggested that SID values
      should be used for feed formulation, at least until more information on TID
      values becomes available.

PMID- 17179554
TI  - Effect of substitution of a soybean hull and grape seed meal mixture for
      traditional fiber sources on digestion and performance of growing rabbits and
      lactating does.
AB  - The aim of this work was to determine what concentration of a mixture of soybean
      hulls and defatted grape seed meal (SHDG) could be included in diets that meet or
      exceed ADL and particle size requirements for rabbits. Four isonitrogenous and
      isofibrous pelleted diets were formulated, with similar ADL concentration and
      particle size (18.3% CP, 42.6% NDF, 7.1% ADL, and 34.9% of particles larger than
      0.315 mm, on a DM basis). Diets contained a constant ratio of soybean
      hulls:defatted grape seed meal (81:19) provided at 0, 13.3, 26.7, or 40% SHDG,
      which was substituted for a 35:35:30 mixture of alfalfa hay, sunflower hulls, and
      wheat straw. Thirty-six rabbits were used to determine nutrient digestibility and
      cecotrophy traits. A feeding trial was carried out using 160 weanling rabbits (30
      d of age; 536 +/- 7.1 g). Milk production was measured in 56 rabbit does.
      Increasing concentrations of SHDG in the diet did not affect digestibilities of
      DM, GE, or NDF or DE that were on average 54.7, 55.2, and 21.6% and 10.2 MJ/kg of
      DM, respectively. Digestibility of CP decreased in diets containing 40% (P =
      0.002) and 26.7% (P = 0.054) SHDG compared with diets containing a lower percent
      of SHDG. Daily recycling of CP through cecotrophy, an indicator of microbial
      protein production, was not affected by SHDG inclusion. Growing rabbits fed 40%
      SHDG had reduced ADFI and ADG compared with rabbits fed 26.7% SHDG or less (106
      vs. 113, 111, or 111 g/d, and 35.8 vs. 37.8, 36.6, or 37.6 g/d, respectively).
      There was no effect on G:F from adding SHDG to the diets. In the 2-wk period
      after weaning, ADG decreased (P = 0.031) for rabbits fed 40% SHDG compared with
      rabbits fed 26.7% SHDG or less (28.4 vs. 32.2, 30.8, of 32.2 g/d), with no effect
      on ADFI or G:F. Type of diet did not influence mortality during the fattening
      period, which averaged 6.25%. Rabbit does fed 40% SHDG had reduced ADFI (411 vs.
      430 g/d; P = 0.023) compared with rabbits fed 26.7% SHDG or less, with no effect
      (P > 0.11) on milk production, weight of the litter at 21 d and at weaning (30
      d), or parturition-effective mating interval. In conclusion, SHDG can be included
      up to 26.7% in diets for fattening rabbits and lactating does that meet ADL and
      particle size requirements.

PMID- 17179555
TI  - Dietary B vitamin needs of strains of pigs with high and moderate lean growth.
AB  - Ten sets of 5 littermate pigs from each of 2 genetic strains were utilized to
      determine the impact of the dietary concentration of 5 B vitamins (riboflavin,
      niacin, pantothenic acid, cobalamin, and folacin) on growth from 9 to 28 kg of BW
      in pigs with high or moderate capacity for lean growth. All pigs (penned
      individually) were reared via a segregated, early weaning scheme, so that the
      lean growth potential of each strain could be expressed. The basal diet provided
      the 5 test vitamins at concentrations of total and estimated bioavailability
      equivalent to a minimum of 100 and 70%, respectively, of their estimated
      requirements (NRC, 1998) for 5- to 10-kg pigs. At a BW of 9 +/- 0.9 kg, pigs
      within each litter were allotted to the basal diet supplemented with sources of
      the 5 test vitamins equivalent to an additional 0, 100, 200, 300, or 400%
      (bioavailable) of the NRC requirements. Pigs from the high lean strain consumed
      less feed (P < 0.05) and gained BW faster (P < 0.02) and more efficiently (P <
      0.01) than pigs of the moderate lean strain. In both lean strains, the rate and
      efficiency of growth were improved (P < 0.01) as dietary B vitamin concentrations
      were increased. However, the dietary B vitamin concentrations needed to optimize
      G:F were greater (P < 0.03) in the high (>470% of NRC, 1998) vs. moderate (270%)
      lean strain. Based on these data, the dietary needs for 1 or more of the 5 B
      vitamins are greater than current NRC (1998) estimates, particularly in pigs
      expressing a high rate of lean tissue growth. The greater need for these vitamins
      is not associated with greater dietary energy intake or body energy accretion
      rate but is potentially due to shifts in the predominant metabolic pathways.

PMID- 17179556
TI  - Nutritional evaluation of high-digestible sorghum for pigs and broiler chicks.
AB  - Two experiments were conducted to evaluate the nutritional quality of 2 varieties
      of Purdue high-digestible sorghum (PHD1 and PHD2) and a normal sorghum, compared
      with corn, in diets of pigs and broiler chicks. In Exp. 1, 12 pigs (average BW,
      55 kg) fitted with ileal T-cannula were fed 4 diets containing 946 g of corn or
      sorghum (PHD1, PHD2, and normal) per kg in a 2-period crossover design (i.e.,
      each pig received 2 diets over a 2-wk period with 6 pigs per dietary treatment)
      to determine apparent ileal or total tract digestibility of nutrients and energy.
      There was no difference in the ileal or total tract digestibility of DM, energy,
      P, Ca, or N among dietary treatments. In Exp. 2, a total of 192 broiler chicks
      were grouped by weight into 8 blocks of 4 cages each with 6 chicks per cage, and
      cages were assigned randomly to 1 of the 4 dietary treatments within each block.
      Chicks were fed corn-soybean meal (SBM) or sorghum-SBM diets for 21 d to
      determine apparent total tract retention and then switched to diets containing
      935 g of the corresponding corn or 1 of the 3 sorghum varieties per kg for 7 d to
      determine apparent ileal digestibility and total tract retention. Apparent ileal
      digestibilities of DM and P, as well as energy, were not different in chicks fed
      diets containing 935 g of corn or 1 of the 3 sorghum varieties per kg. However,
      apparent total tract retention of DM, energy, and N in chicks fed corn was
      greater (P < 0.05) than those fed 1 of the 3 sorghum varieties. Although the
      apparent ME content of corn was greater than PHD1 and normal sorghum (P < 0.01),
      it was not different from PHD2 sorghum. There was no difference in apparent total
      tract retention of DM between chicks fed the corn-SBM and PHD-SBM diets, but it
      was greater (P < 0.05) in chicks fed the corn-SBM diet than those fed the normal
      sorghum-SBM diet. Apparent total tract retention of N in chicks fed the PHD1-SBM
      diet was lower (P < 0.05) than in those fed the corn-SBM diet but greater (P <
      0.05) than in chicks fed the normal sorghum-SBM meal diet. No difference in the
      apparent ME content between the corn-SBM and PHD2-SBM diets was observed, but it
      was greater (P < 0.05) for the corn-SBM diet than the PHD1- or normal sorghum-SBM
      diet. Weight gain, feed intake, and feed efficiency were not different in chicks
      fed the corn-SBM or sorghum-SBM diets. Sorghum could serve as a substitute for
      corn in cereal grain-SBM diets for pigs and broiler chicks.

PMID- 17179557
TI  - The impact of dietary protein source on observed and predicted metabolizable
      energy of dry extruded dog foods.
AB  - Fifty-five observations were used to determine the ME content of 8 foods
      containing different protein sources. The major protein sources tested included
      low-oligosaccharide whole soybeans; 2 low-oligosaccharide, low-phytate whole
      soybeans; 2 conventional soybean meals; low-ash poultry meal; low
      oligosaccharide, low-phytate soybean meal; and conventional whole soybeans. The
      ME content of all foods ranged from 3,463 to 4,233 kcal/kg of DM. The first
      objective was to utilize the observed ME data and test the accuracy of the
      modified Atwater equation. In this study, the modified Atwater equation generally
      underpredicted ME compared with the observed ME (residual mean = 247 kcal/kg).
      The second objective was to use individual data to develop an equation, based on
      the chemical composition of the food, to predict the ME content of the foods. A
      multivariate regression analysis was used to predict ME content based on chemical
      composition. Five models were fitted to the data. Model 1 included CP, ether
      extract (EE), and crude fiber (CF). Because the foods varied in protein sources,
      and the ratio of total AA (TAA) to non-AA (NAA) CP ranged from 3.5:1 to 14.4:1,
      it was hypothesized that accounting for the proportion of TAA and NAA in CP would
      improve the fit of the model. Therefore, model 2 included TAA, NAA, EE, and CF.
      Defining CP in terms of TAA and NAA improved the r2 of the model from 0.46 to
      0.79. Subsequently, models 3, 4, and 5 replaced the CF term with ADF, NDF, and
      hemicellulose (HEM). Model 3 included TAA, NAA, EE, and NDF. Model 4 included
      TAA, NAA, EE, ADF, and HEM. Model 5 included TAA, NAA, EE, and HEM. Defining
      dietary fiber in terms of HEM improved the r2 of model 2 from 0.79 to 0.81.
      Residual analysis suggested that replacing the CF term with HEM (model 5)
      improved the prediction of ME content. In contrast, defining fiber in terms of
      NDF (model 3) did not result in an improvement over model 2, whereas the ADF term
      (model 4) did not (P > 0.34) contribute to the overall model. Fractionating CP
      into TAA and NAA components further defined the chemical composition of the food.
      These data suggest that defining protein composition improves the accuracy of
      predicting the ME content of dog foods.

PMID- 17179558
TI  - Technical note: A system for continuous recording of ruminal pH in cattle.
AB  - Continuous recording of ruminal pH in cannulated cattle has been practiced to
      study rumen metabolism. However, most systems reported did not permit animal
      mobility during pH recording. Therefore, the objective of this study was to
      develop a continuous rumen pH data acquisition system that permitted animal
      mobility during data acquisition. A further objective was to compare the pH
      readings obtained using the continuous recording system to readings obtained at
      the same time using spot sampling. The continuous recording system was composed
      of a heavy-duty electrode and a data logger. The electrode was attached to a 0.5
      kg weight to help maintain the electrode in the ventral sac of the rumen. The
      electrode was connected via a 0.5-m cable to a lightweight data logger that was
      mounted on the animal's back using a belt wrapped around the girth. The data
      logger was battery powered and could hold over 13,000 pH data values. A personal
      digital assistant was used to configure and download data from the data logger
      during the experiment. Ruminal pH was continuously recorded (every 10 s) using a
      dry Holstein cow fed alfalfa hay ad libitum in a 3-d experiment to compare the
      performance of the continuous system to spot samples taken from the ventral sac
      of the rumen, the same location as the continuous electrode. The spot samples
      were collected 3 times per d for 3 d. At every sampling time, 3 replicate samples
      were collected, pH was determined immediately using a handheld pH meter, and
      readings were averaged (n = 3) and compared with the average of the 3 pH readings
      recorded using the continuous system at the same time. The pH recorded by spot
      sampling (6.63 +/- 0.04) was greater (P = 0.009) than that of the continuous
      system (6.56 +/- 0.03), with a correlation of r = 0.88 (P = 0.002). The
      continuous recording system has the potential to facilitate measurement of
      ruminal pH in free-roaming cattle.

PMID- 17179559
TI  - Evidence of phenotypic relationships among behavioral characteristics of
      individual pigs and performance.
AB  - The objective of this research was to estimate phenotypic relationships among
      backtest scores (BTS), resident-intruder test scores (RIS), growth rate, LM area,
      and backfat in pigs. Little is known about the relationships among measures of
      behavioral characteristics of individual pigs and economically important traits.
      However, it may be expected that a pig's behavior affects its performance and
      that of its pen mates. The backtest was used in this experiment because it was
      previously shown to be a measure of individual stress-coping behavior and was
      related to lean gain. The resident-intruder test was used because it is a measure
      of a pig's tendency for aggressive behavior toward an unfamiliar pig. Each test
      was performed twice on pigs (n = 150) from 20 litters, and complete performance
      data was available on 140 pigs. Between 7 and 14 d of age, the backtest was
      performed by placing each pig in a supine position and gently restraining it for
      60 s. The number of escape attempts (bouts of struggling) and total time spent
      struggling were recorded. The BTS was the summation of escape attempts during
      both tests. Resident intruder tests were assessed when pigs were between 30 and
      50 d of age. A solid divider was placed in the resident pig's pen. The resident
      was placed alone on 1 side of the divider, away from its penmates. An intruder
      pig of the same sex and smaller size was then placed into the pen. When an attack
      was initiated by the resident, the pigs were immediately separated, the test was
      terminated, and a score of 1 was recorded. If no attack occurred by 5 min, the
      test was terminated and was given a score of zero. The cumulative score from both
      tests was the RIS. Dam effects influenced BTS (P < 0.01) and RIS (P < 0.03).
      Preweaning ADG of pigs with a BTS of 8 was 120 g greater than that of pigs with a
      BTS of 2. However, ADG from 20 to 76 d of age was 131 g greater in pigs with BTS
      = 2 than in pigs with BTS = 8. Lean gain of pigs with RIS = 2 was 25 g/d greater
      than in those with RIS = 0 or 1. This resulted in pigs with RIS = 2 having 1.6 kg
      more acceptable, standardized, fat-free lean. Conflicting results were found when
      relating the BTS to performance. However, with the RIS, greater aggression toward
      other pigs was associated with better performance. It was concluded that an
      unfavorable phenotypic relationship existed between RIS and lean growth.

PMID- 17179560
TI  - Effect of the seaweed Ascophyllum nodosum on lambs during forced walking and
      transport.
AB  - The objective of this study was to determine the effect of feeding Ascophyllum
      nodosum (ANOD) to lambs at 0 (control), 0.5, 1, or 2% of DMI/d for 2 wk on lamb
      physiology in response to forced walking and transport during hot weather. Forty
      four lambs (26 kg +/- 4.3) were used, and each lamb swallowed 3 gelatin capsules
      filled with ANOD or their normal 16% CP, pelleted grain ration twice daily, with
      the amount of ANOD dependent on the treatment. The amount of ANOD did not affect
      ear canal temperature or cortisol concentrations during 60 min of forced walking.
      The range between the minimum and maximum ear canal temperature for each lamb
      during 12 h of transport was narrower in lambs receiving the 2% ANOD than the
      control group (P = 0.05), and the 2% ANOD group also had lower (P = 0.05) ear
      canal temperatures than the control group during hot periods of transport. After
      4 (P = 0.09) and 8 h (P = 0.05) of transport, the control group tended to have
      greater cortisol concentrations than the 2% ANOD group. Many differences among
      treatments were found in plasma protein, albumin, calcium, phosphorus, glucose,
      blood urea nitrogen, aspartate aminotransferase, magnesium, sodium, potassium,
      and chloride concentrations posttransport; mainly, the control and 0.5% ANOD
      groups had greater (P < 0.05) concentrations than the other 2 treatments.
      Aldosterone concentrations were greater in the control and 0.5% ANOD group than
      in the 1 and 2% ANOD groups before transport, whereas the concentrations were not
      different after transport, suggesting pretransport concentrations were lowered by
      supplementation. The 1 and 2% ANOD groups lost more BW than the control group as
      a result of transport (P = 0.04). After transport, no differences were observed
      in the latency for lambs to drink, eat, or lay. There was a suppression of the
      IgG and IgM antibody responses at 4 and 7 d after administration of ovalbumin,
      with greater ANOD supplementation rates suppressing antibody response the
      greatest. Although ANOD decreased ear canal temperature in hot periods of
      transport, stabilized electrolyte concentrations, and decreased cortisol
      throughout transport, it also suppressed the antibody response indicating that
      the effect of ANOD on immune function merits further investigation.

PMID- 17179561
TI  - Feeding live cultures of Enterococcus faecium and Saccharomyces cerevisiae
      induces an inflammatory response in feedlot steers.
AB  - Two experiments were conducted to investigate the effects of oral supplementation
      of the lactic-acid-producing bacterium Enterococcus faecium EF212 alone or in
      combination with Saccharomyces cerevisiae (yeast) on mediators of the acute phase
      response in feedlot steers. Eight fistulated steers were used to study the
      effects of E. faecium alone or with yeast in a crossover design with 2 Latin
      squares, 4 steers within each square, and 2 periods. The length of each period
      was 3 wk, with a 10-d adaptation and an 11-d measurement period. The experimental
      diet contained 87% steam-rolled barley, 8% whole-crop barley silage, and 5%
      supplement (DM basis). In Exp. 1, treatments were control vs. the lactic-acid
      producing bacterium E. faecium (6 x 10(10) cfu/d). In Exp. 2, treatments were
      control vs. E. faecium (6 x 10(10) cfu/d) and S. cerevisiae (6 x 10(10) cfu/d).
      The bacteria and yeast supplements were blended with calcium carbonate to supply
      6 x 10(10) cfu/d when top-dressed into the diet once daily at the time of feeding
      (10 g/d). Steers fed the control diet received only carrier (10 g/d). Blood
      samples were collected from the jugular vein on d 17 and 21 of each period, and
      serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), haptoglobin, and
      alpha1-acid glycoprotein (alpha1-AGP) were measured. Supplementation of feed with
      E. faecium had no effect on concentrations of SAA, LBP, haptoglobin, or alpha1
      AGP in plasma compared with those of controls. However, feeding E. faecium and
      yeast increased (P = 0.02) plasma concentrations of SAA, LBP, and haptoglobin but
      had no effect on plasma alpha1-AGP. In conclusion, oral supplementation of E.
      faecium alone had no effect on the mediators of the acute phase response that
      were measured, whereas feeding of E. faecium and yeast induced an inflammatory
      response in feedlot steers fed high-grain diets. Further research is warranted to
      determine the mechanism(s) by which E. faecium and yeast stimulated production of
      acute phase proteins in feedlot steers.

PMID- 17179562
TI  - Effects of social isolation and restraint on adrenocortical responses and
      hypoalgesia in loose-housed dairy cows.
AB  - Effects of social isolation or restraint, applied outside the home pen, on
      adrenocortical and nociceptive responses were examined in 28 loose-housed dairy
      cows. Treatments lasted 15 min and consisted of social isolation in novel
      surroundings or restraint by the head in a test pen. A control treatment was
      applied in the test pen as well. Each cow was exposed to all treatments in a
      balanced order, with 3 to 4 d between treatments. Compared with the control
      treatment, social isolation in novel surroundings led to increased plasma
      concentration of cortisol (P < 0.001) as well as to indications of hypoalgesia
      [posttreatment lack of decrease in latency to respond toward nociceptive laser
      stimulation, a tendency for decreased frequency of kicking in the pauses between
      laser stimulations (P = 0.06), and an increased proportion of leg moving (least
      possible active response) after treatment (P = 0.04)]. Indications of hypoalgesia
      were also observed after restraint (reduced kicking in response to laser
      stimulation, P = 0.04); however, the indications were to a lesser extent than
      after social isolation, and restraint treatment did not lead to increased plasma
      concentration of cortisol. For control and restraint treatment, an initial
      increase (P < 0.02) in plasma concentration of cortisol was found, suggesting
      effects of pretreatment factors such as handling. No correlations between
      adrenocortical and nociceptive responses toward social isolation were found. The
      results confirm earlier reports stating that nociceptive changes induced by
      environmental challenges can be shown in dairy cows, even when they are kept in
      groups and removed from the home pen during the study of stress responses.
      However, testing outside the home pen seemed to affect the nociceptive and
      adrenocortical responses, thereby suggesting that care should be taken to avoid
      effects of pretreatment situational factors.

PMID- 17179563
TI  - Suitability of electronic mini-boluses for early identification of lambs.
AB  - Three types of ceramic mini-boluses, B1 [13.8 g; 10.5 x 51.0 mm (o.d. x length)],
      B2 (16.2 g; 12.2 x 42.2 mm), and B3 (20.1 g; 11.2 x 56.4 mm), were used to
      electronically identify as soon as possible after birth a total of 545 lambs of 3
      breeds: Ripollesa (meat breed, n = 274), Manchega (dairy breed, n = 129), and
      Lacaune (dairy breed, n = 142). Boluses were administered by a trained operator
      using a balling gun or directly by hand. Lambs were also identified with 2 types
      of plastic ear tags in the left (temporary, 1.5 g) and the right (permanent, 4.1
      g) ears. Lamb and identification device performances were checked during suckling
      (to wk 5 or 7) and fattening. At 24 kg of BW, lambs were slaughtered (n = 385) or
      kept for breeding (n = 144). No differences in performance were observed between
      the 2 dairy breeds, and their data were pooled. Minimum BW for bolus
      administration was lower in dairy than in meat lambs (P < 0.001). Across breeds,
      B1 and B3 did not differ in lamb age (27 d) and weight (9.2 kg) at
      administration, but B2 required older and heavier lambs (33 d and 11.1 kg; P <
      0.01). Boluses did not affect lamb performance, but final readability at
      slaughter differed between B1 and B2 (97.7 and 95.2%, respectively) and B3
      (100%), and between ear tags (temporary, 98.1; permanent, 100%). Bolus recovery
      was 100% in all cases, but the proportion of boluses found in the reticulum
      varied among bolus type (83.3 to 93.8%; P < 0.05). Three B1 (2%) were recovered
      from the abomasum. In a second experiment, effects of the intermediate mini-bolus
      (B2) on diet digestibility were evaluated. Digestibility of control and bolus
      administered, Manchega ram lambs (14.9 kg of BW; n = 8) fed ad libitum with 2
      pelleted concentrates and barley straw was assessed in digestibility crates. Feed
      intake and nutrient digestibility were measured in four 21-d periods, during
      which lambs received the 2 diets consecutively. No differences in intake, growth
      performance, or nutrient digestibility were observed between control and bolused
      lambs. In conclusion, the B3 mini-bolus proved to be an efficient device for
      identification of lambs before weaning (recommended age, >4 wk; recommended BW,
      >10 kg), allowing a reliable traceability of dairy and meat lambs until
      slaughter.

PMID- 17179564
TI  - Postweaning growth check in pigs is markedly reduced by intermittent suckling and
      extended lactation.
AB  - The objective of this study was to determine whether intermittent suckling (IS)
      combined with an extended lactation can reduce postweaning growth check in pigs.
      Three weaning regimens [conventional weaning (CW), IS with 6-h separation
      intervals (IS6), and IS with 12-h separation intervals (IS12)] were compared. In
      CW (n = 17 litters), litters had continuous access to the sow until weaning (d
      21, d 0 = farrowing). In IS6 and IS12, litters were separated from the sow for 12
      h/d, beginning at d 14 and lasting until weaning (d 41 to 45). Litters were with
      the sow from 1400 to 2000 and from 0200 to 0800 (IS6, n = 14) or between 2000 and
      0800 (IS12, n = 14). Litter size was standardized within 2 d after farrowing by
      crossfostering, resulting in an average litter size of 10.9 +/- 1.8 piglets.
      Piglets had ad libitum access to creep feed from d 7 onward. One week after the
      onset of IS (d 20), creep feed intake was increased in litters from both IS
      groups compared with CW litters (P < 0.05). Both IS groups consumed considerable
      amounts of creep feed before weaning (d 41 to 45). Total feed intake before
      weaning was greater (P = 0.004) in IS12 (3,808 +/- 469 g/piglet) than in IS6
      (2,717 +/- 404 g/piglet). In comparison, CW litters consumed 18 +/- 9 g/piglet
      before weaning (d 21). Irrespective of weaning regimen, total feed intake of
      litters before weaning was highly correlated with post-weaning feed intake (P <
      0.001). Furthermore, in all treatment groups, total preweaning feed intake was
      correlated with postweaning growth (P < 0.10). Irrespective of treatment, piglets
      suckling anterior teats grew faster than piglets suckling middle or posterior
      teats during the first 2 wk of lactation. Body weights at the end of the
      experiment (d 55) were similar among weaning regimens. Onset of IS induced a
      growth check in both IS groups (34% for IS12 and 22% for IS6). Only a mild growth
      check was observed after weaning of IS litters (14% for both IS groups). However,
      a serious growth check (98%) was observed after weaning of CW litters. Results of
      the current study indicate that IS stimulated feed intake during lactation,
      providing a more gradual transition to weaning. Because the IS6 regimen did not
      prevent the growth check after the onset of IS and is rather laborious, we
      suggest that IS12 might be preferable for a practical implementation of IS.

PMID- 17179565
TI  - Serum hormone concentrations relative to carcass composition of a random
      allotment of commercial-fed beef cattle.
AB  - Cattle (n = 995 steers and 757 heifers) were randomly selected from a commercial
      abattoir (Emporia, KS) to determine the relationships between USDA quality and
      yield grade characteristics and serum concentrations of leptin, IGF-I, and GH.
      Animals were randomly selected postexsanguination on the slaughter line on 4
      occasions (March, May, August, and January). Blood was collected at
      exsanguination and transported to the University of Missouri for analysis. Sex
      and hide color were recorded. Carcass data included HCW, 12th-rib fat thickness,
      KPH, LM area, and marbling score, which were collected from each carcass
      approximately 24 h postmortem. Average serum leptin concentrations were greater
      (P = 0.008) for heifers (11.9 ng/mL) than steers (10.9 ng/mL). Heifers had
      lighter carcasses (331.9 vs. 352.2 kg, P < 0.001), greater 12th-rib fat
      measurements (1.3 vs. 1.1 cm, P < 0.001), greater KPH (2.5 vs. 2.4%, P < 0.001),
      and more marbling (Small(40) vs. Small(10), P < 0.001) than steers. Positive
      correlations (P < 0.01) existed between leptin concentration and marbling score
      (r = 0.28), 12th-rib fat depth (r = 0.37), KPH (r = 0.23), and USDA yield grade
      (r = 0.32). Negative correlations were found between leptin and IGF-I (r = -0.11;
      P < 0.001) and leptin and GH (r = -0.32; P < 0.001). Negative correlations (P <
      0.01) were observed for IGF-I and KPH (r = -0.23) and marbling score (r = -0.20),
      whereas GH was most highly negatively correlated with KPH (r = -0.23; P < 0.001).
      Leptin concentration accounted for variation (P < 0.001) in a model separating
      least squares means across USDA quality grade, separating USDA standard (8.5
      ng/mL), select (10.3 ng/mL), low choice (12.2 ng/mL), and upper 2/3 choice/prime
      (>12.9 ng/mL) carcasses. There was no difference (P = 0.31) observed in leptin
      concentrations between the upper 2/3 choice and prime carcasses (12.9 and 14.2
      ng/mL, respectively). Relationships within endocrine profiles and between
      endocrine concentrations and carcass quality characteristics may prove to be a
      useful tool for the prediction of beef carcass composition.

PMID- 17179566
TI  - Afternoon harvest increases readily fermentable carbohydrate concentration and
      voluntary intake of gamagrass and switchgrass baleage by beef steers.
AB  - Our objective was to determine if harvest in the morning (AM, 0600) vs. the
      afternoon (PM, 1800) affects composition and voluntary DMI of gamagrass (GG) or
      switchgrass (SG) stored as baleage. Iuka GG (Tripsacum dactyloides L.) and Alamo
      SG (Panicum virgatum L.) were cut with a mower-conditioner, immediately round
      baled, wrapped in plastic, and stored as baleage. Beef steers (255 +/- 7 kg of
      BW) were assigned (5 steers/treatment) to GG/AM, GG/PM, SG/AM, or SG/PM. Ad
      libitum intake was measured for 21 d (7-d adjustment and 14-d intake estimate)
      followed by 7-d adjustment and 5-d digestion and N balance study. Chewing
      behavior was recorded during the balance study. Compared with AM, PM had more (P
      < 0.01) starch (9.3 vs. 4.7 g/kg of DM), total nonstructural carbohydrate (30.4
      vs. 19.0 g/kg of DM), and monosaccharides (17.1 vs. 11.2 g/kg of DM). Compared
      with AM, PM had less (P = 0.05) acetate (13.0 vs. 18.6 g/kg of DM) and propionate
      (0.29 vs. 0.82 g/kg of DM) and tended (P < 0.13) to have less lactate (2.9 vs.
      3.5 g/kg of DM) and butyrate (3.9 vs. 5.1 g/kg of DM). Compared with SG, GG had
      more (P = 0.01) DM (324 vs. 242 g/kg of baleage), CP (114 vs. 97 g/kg of DM),
      lactate (4.8 vs. 1.6 g/kg of DM), starch (9.4 vs. 4.7 g/kg of DM), total
      nonstructural carbohydrate (34.2 vs. 15.2 g/kg of DM), and monosaccharides (20.8
      vs. 7.4 g/kg of DM). However, GG had a lower (P = 0.01) pH (5.32 vs.5.79) and
      less (P < 0.01) ethanol (18.7 vs. 27.3 g/kg of DM), acetate (12.3 vs. 19.2 g/kg
      of DM), propionate (0.00 vs. 1.11 g/kg of DM), and butyrate (0.6 vs. 8.4 g/kg of
      DM). Daily DMI (2.16 vs. 1.83% of BW) and digestible DMI (1.15 vs. 0.95% of BW)
      were greater (P = 0.03) for PM than AM. Plasma urea N concentrations at the end
      of the ad libitum intake phase were greater (P = 0.01) for AM (3.91 mM) than for
      PM (2.31 mM) and greater (P = 0.07) for GG (3.51 mM) than for SG (2.71 mM).
      Steers fed PM spent more time eating (P = 0.04) and less time resting (P = 0.01)
      during meals than steers fed AM. Apparent digestibility of DM and fiber
      components was not affected (P < 0.18) by treatment. Apparent digestibility and
      retention of N decreased from PM to AM for SG, but increased for GG (P = 0.05).
      Retention of N as a percentage of N intake or N digested decreased more from PM
      to AM for SG than for GG (P < 0.05). We conclude that increased nonstructural
      carbohydrate content of the PM harvest of these grasses stored as baleage caused
      increased voluntary intake and improved use of dietary N by beef steers.

PMID- 17179567
TI  - Thalidomide. Treat with caution!

PMID- 17179570
TI  - From Trousseau to angiogenesis: the link between the haemostatic system and
      cancer.

PMID- 17179571
TI  - Application of guidelines on preoperative antibiotic prophylaxis in Leon,
      Nicaragua.
AB  - BACKGROUND: To determine adherence to the guideline for preoperative antibiotic
      use in Nicaragua. METHODS: An observational study in the University Hospital of
      Leon, Nicaragua. All surgical patients in the departments of general surgery,
      orthopaedics, gynaecology and obstetrics, and paediatrics during a four-week
      period were included. Patients with infections prior to surgery were excluded.
      Main outcome measures were the proportion of patients that received appropriate
      preoperative antibiotics based on wound classification, suspected pathogens,
      administered antibiotics (type and dose), therapy duration and timing according
      to the local protocol. RESULTS: In the study, 297 patients received a total of
      395 antibiotics with 2595 doses for a total of 1087 days. Only 68% of patients
      received antibiotic prophylaxis for indications mentioned in the protocol.
      Antibiotics were given without indication or as treatment in 23%. In 9% of the
      cases no preoperative antibiotic therapy was given (no indication for 6%, but
      indicated for 3%). Of the 201 patients with an indication for prophylaxis, 25%
      received more antibiotic therapies than indicated. Antibiotic choice was
      discordant with the protocol in 69%, dose in 20%, and both the moment of
      administration and duration in 78%. Overall adherence was achieved in 7% of
      patients. Complete protocol violations were observed in 12%. The 243 patients in
      the prophylaxis group received 1707 doses, 83% of which were administered
      unnecessarily. CONCLUSION: Protocol violations are frequent in preoperative
      antibiotic prophylaxis in Nicaragua leading to considerable overprescription.
      Educational strategies to reinforce protocolised antibiotic use are essential for
      reducing costs and antibiotic resistance rates.

PMID- 17179572
TI  - Safety of electroconvulsive therapy in patients with asthma.
AB  - BACKGROUND: Patients with depression and other psychiatric disorders being
      considered for electroconvulsive therapy (ECT) may also have asthma. Since ECT
      requires the administration of general anaesthesia, it is assumed that extra care
      should be taken with asthmatic patients before and during ECT. We sought to
      investigate the safety of ECT in asthmatic patients. METHODS: A retrospective
      review was conducted of the medical records of all of the patients with currently
      active and managed asthma who underwent ECT for severe depressive syndromes at
      Mayo Clinic, Rochester, Minnesota, between 1 January 1998, and 30 June 2006.
      RESULTS: Thirty-four patients with asthma who also underwent ECT were identified.
      Of these, 27 (79%) were women. The median age was 45 years (range 23-84 years).
      All 34 patients were using asthma medications daily at the time of ECT. The 34
      patients underwent a total of 459 ECT sessions. Four (12%) patients experienced
      exacerbation of their asthma on a total of five occasions. Each exacerbation was
      successfully treated with standard asthma medications, and all four patients
      completed their courses of ECT. CONCLUSION: ECT in patients with asthma appears
      to be safe. Although exacerbation of asthma after ECT was rare in our series, a
      prospective study would be needed to determine the precise risk of pulmonary
      complications of ECT in asthmatic patients.

PMID- 17179574
TI  - Thalidomide as treatment for digestive tract angiodysplasias.
AB  - An 80-year-old man with von Willebrand's disease was admitted with severe
      melaena. Despite suppletion with von Willebrand concentrate he continued to be
      dependent on blood transfusions. Endoscopic examination did not show a bleeding
      focus. Video capsule endoscopy showed active bleeding from angiodysplasias in the
      proximal section of the small intestine. Ultimately, treatment with thalidomide
      was initiated at a dose of 100 mg/day. Soon after starting treatment his stools
      became normal and his haemoglobin level stabilised. No bleeding problems occurred
      for 11 months, after which the thalidomide treatment was stopped because of the
      potential side effects. Two months later he again developed melaena and treatment
      with thalidomide was restarted with a successful outcome. Trying to lower the
      dose to 50 mg resulted in rebleeding after three months with stabilisation after
      increasing the dose to 100 mg again. Monotherapy with thalidomide improves the
      clinical picture but may not be sufficient in the long term. Additional therapy,
      such as argon plasma coagulation or the use of the novel drug lenalidomide, might
      be necessary.

PMID- 17179573
TI  - Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum.
AB  - We report successful treatment of a refractory myelodysplastic syndrome
      associated pyoderma gangrenosum with the combination of thalidomide and
      interferon-alpha2a in a single patient. A non-healing wound developed on a 40
      year-old woman's left thumb after minor trauma. Massive ulcerovegetative lesions
      developed after reconstruction surgery. Histopathological examination of the bone
      marrow and cytogenetic studies revealed an atypical
      myeloproliferative/myelodysplastic syndrome. The skin lesions resolved
      dramatically after two months of thalidomide and interferon-alpha2a combination
      therapy and the haematological status improved.

PMID- 17179575
TI  - Right subclavian vein cannulation? Insertion of a central venous catheter with
      inadvertent cannulation of the subclavian artery.

PMID- 17179576
TI  - Blue rubber bleb nevus syndrome co-existing with celiac disease.
AB  - BACKGROUND: Anaemia caused by iron deficiency is one of the most common disorders
      in the world. We describe a patient with iron deficiency anaemia in whom
      absorption was limited due to celiac disease, superimposed to chronic blood loss
      due to the blue rubber bleb nevus syndrome, a rare syndrome characterised by
      multiple cutaneous venous malformations in association with visceral lesions.
      CASE REPORT: A 54-year-old patient with severe iron deficiency anaemia showed
      marked rubbery cutaneous lesions on the body surface, extremities, under and on
      the left side of the tongue as well as in the stomach and duodenum. The
      appearance and pathological examination of the lesions were consistent with the
      diagnosis of blue rubber bleb nevus syndrome (BRBNS). Biopsy of the mucosa of the
      duodenum showed celiac disease. No association between celiac disease and BRBNS
      has been previously described. CONCLUSION: Combined loss of iron and
      malabsorption from the gastrointestinal tract can lead to severe iron deficiency.
      Early recognition of both diseases can result in early treatment. Patients can
      recover completely with iron suppletion and a gluten-free diet. Recognising
      typical BRBNS skin lesions would provide a potential diagnosis and could prevent
      unnecessary procedures or invasive surgery.

PMID- 17179578
TI  - [Case report of simultaneous coronary artery bypass grafting with cardiopulmonary
      bypass and total thymectomy in patient with myasthenia gravis].
AB  - In this article we want to describe the successful simultaneous operation of
      coronary artery bypass grafting with cardiopulmonary bypass and thymectomy in
      patient with ischemic heart disease and myasthenia gravis. Myasthenia gravis
      complicates the course of anesthesia and operation, because of the inadequate
      restoration of muscle function, especially of respiratory and swallowing muscles,
      inducing the prolonged mechanical ventilation, gastrooesophageal reflux and
      pulmonary infection. There are lot of different techniques of the anesthesia
      during myasthenia gravis - no use of any myorelaxantes, restriction of opioids,
      use an inhalation anaesthetics and propofol, and continuous monitoring of
      neuromuscular junction function. Till now it is discussable question of necessity
      and the time of thymectomy. This case from clinical practice shows, that the
      correct choice of tactics of pre- and postoperative treatment makes simultaneous
      coronary artery bypass grafting with cardiopulmonary bypass and thymectomy
      possible.

PMID- 17179577
TI  - Effectiveness of percutaneous ethanol injection therapy in benign nodular and
      cystic thyroid diseases: 12-month follow-up experience.
AB  - This study was designed to clarify the long-term efficacy of percutaneous ethanol
      injection (PEI) therapy in benign nodular and cystic thyroid diseases. Solid
      nodule and complex cyst were classified into three groups in accordance with
      volume reduction. In solid nodule (n = 38) and complex cyst (n=8), initial volume
      was significantly reduced to final volumes, and volume reduction persisted during
      follow-up period. Complete response, partial response and no response were as
      follows: 21 %, 63 %, 15 % in solid nodule; 37,5 %, 50 %, 12,5 % in complex cyst,
      respectively. Differences of volume reduction according to initial volume (>10 mL
      vs <10 mL) were significant. Correlation between initial and final volumes, and
      between initial volume and volume reduction were also significant. Complications
      were developed in 10,5 % of patients but there were not permanent complications.
      In conclusion, our data suggest that PEI therapy could be an effective and safe
      therapeutic modality for benign nodular and cystic thyroid diseases especially
      when initial volume is more than 10 mL.

PMID- 17179579
TI  - Contemporary experimental models of traumatic brain injury.
AB  - This review article aims to bring investigators' attention to experimental models
      of traumatic brain injury, widely employed in research in western countries and
      almost unknown in Eastern Europe. We describe the most successful animal models
      that cause neurotrauma by applying mechanical energy to the head, skull or dura.
      It attempts to provide a short compendium of the main characteristics of each of
      these experimental models of TBI in respect to main human neurotrauma features,
      histological findings and behavioral impairment in neurologic motor and cognitive
      function.

PMID- 17179580
TI  - [Spontaneous ruptures of the urinary bladder in the routine forensic
      examination].
AB  - This article analyses three cases of death following a spontaneous rupture of the
      urinary bladder. One case is based on an extensive tamponade of the bladder eight
      days after a transurethral resection of the prostate gland. Two other cases of
      death by spontaneous rupture resulted from increased alcohol consumption. The
      paper presents an overview of pathomorphological findings such as the typical
      intraperitoneal rupture localisation at the posterior wall of the urinary bladder
      or bladder dome and the subsequent diagnosed causes of death. In addition
      predisposing (anamnestic) influencing factors such as chronic alcoholism are
      highlighted and their relevance for the clinical urologist and the forensic
      pathologist are discussed.

PMID- 17179581
TI  - [Influence of antioxidants on the development of benign prostatic hyperplasia].
AB  - The main objectives of the study was the evaluation of concentration of
      endogenous antioxidants (Vitamins E, A, C and Beta-carotene) in the blood plasma
      of elderly men and to determine their roles in the development of benign
      prostatic hyperplasia. There were carried out investigations in 110 men during
      2003-2006 in the Urological Clinic of the Tbilisi State Medical Academy. 71
      patient entered into the main group (65-81 years old), who were diagnosed for
      benign prostate hyperplasia. The control group included 30 men (60-80 years old)
      who did not suffer from the typical signs of benign prostatic hyperplasia.
      Besides, to evaluate normal levels of endogenous antioxidants (Vitamins E, A, C
      and Beta-carotene) concentration in the blood plasma additionally were studied
      young practically healthy 10 persons (20-35 years old), they compiled the second
      control group. Our study showed that endogenous antioxidants concentration
      reduces in the blood plasma with the age, this reduction becomes more obvious
      with the clinical detection of prostate benign hyperplasia. It is recommended for
      elderly patients to control periodically the endogenous antioxidants level
      (Vitamins A, C, E and Beta-carotene) in the blood plasma and in the case of
      changes to get food enriched with vitamins or combined vitamins preparations.
      This will be accomplice factor for the prophylactic of benign prostatic
      hyperplasia. This will be prophylactic activity during the conservative treatment
      process (by alpha-adrenoceptor blocking drugs, phytotherapy medicines, 5 alpha
      reductase inhibitors and others). Inclusion of vitamins complexes which contains
      antioxidants is necessary. Prescription of antioxidants complex after the
      operative treatment will accelerate the healing process and reduce the
      rehabilitation period.

PMID- 17179582
TI  - Estimate the insulin absorption in diabetic patients on peritoneal dialysis.
AB  - Good control of blood glucose obtains both with subcutaneus and with
      intraperitoneal insulin administration. Intraperitoneally administered insulin is
      absorbed more rapidly and evenly than subcutaneously administered insulin. It
      passes directly into the portal vein system. But insulin requirement in
      peritoneal insulin administration is higher then in subcutaneous. Factors
      affecting this insulin absorption are unclear, and our aim was to find the
      relationship of insulin absorption with the parameters, which theoretically might
      be play role in insulin absorption process. 10 diabetic patients on peritoneal
      dialysis were studied. Transport status was determined by a standard 4-hour
      peritoneal equilibration test (PET). Dialysate insulin was analyzed using the
      enzyme-linked immunosorbent assay (ELISA). As it was expected, intraperitoneal
      insulin absorption is related with membrane transport status, glicemia, infusion
      volume of dialysate and insulin dose. According to our results obese and
      dislipidemia are not important factors in insulin absorption process.

PMID- 17179583
TI  - [About correlation of dysfunction of the thyroid gland with fibrocystic diseases
      in women].
AB  - The reference data contain a lot of information on the interrelation between
      destroying of a thyroid gland and fibrocystic diseases. However contradictions in
      these data proves that this issue is not solved completely. The aim of the given
      study was the investigation of interrelations between frequency of occurrence of
      pathology of a functional condition of the thyroid gland and the frequency of
      occurrence of fibrocystic diseases. 90 women aged 23-50 were investigated.
      Concentration of thyroxin (FT4), thyrotrophic hormone (TSH), titers of antibodies
      to thyreoperoxidase, microsomal fraction of thyreocytes and thyreoglobulin were
      measured by ELISA. Palpation and ultrasonic investigations of thyroid and mammary
      glands were used, morphology of central formations of mammary glands according to
      indications was also carried out. A special questionnaire was completed for each
      patient. Our investigations showed that along with the declining of function of
      thyroid gland and the increased level of TSH in the blood, the risk of
      development of fibrocystic diseases is increased twice.

PMID- 17179584
TI  - [Optimization of urogenital chlamydiosis diagnosis in reproductive age women].
AB  - The aim of the study is to optimize laboratory diagnosis of urogenital
      chlamydiosis (UGH) in reproductive age women. 133 women 18-49 years old have been
      investigated. Colpitis were diagnosed in 43-40, 8% of patients, cervicitis and
      cervical pathology in 61-46,9%, PID in 59-45,4% .For diagnosis of UGH we use
      polymerase chain reaction (PCR) method. Results of investigation show, that
      analisis of urethral specimens together with cervical specimens increase the
      detection of Chlamydia trachomatis in 13,6%; performance of analysis in second
      phase of menstrual cycle increase the detection of Chlamydia trachomatis in
      15,4%; use of magnitotherapy increase detection of Chlamydia trachomatis in 25%.
      We use magnitotherapy in cases of chronic UGC with reproductive function failure
      and /or suspicion of persistent form of UGH. For improvement of diagnosis of UGH
      in reproductive age women we recommend performing analysis taking specimens from
      urethra and cervix in second phase of menstrual cycle. In case of chronic UGH and
      /or suspicion of persistent form of UGH we recommend use of magnitotherapy and
      then analysis for chlamydial infection.

PMID- 17179585
TI  - [Influence of the soybean flavonoid supplement on the synthesis of nitric oxide
      (NO) in the patients with atherosclerosis].
AB  - 66 patients of 40-77 age group with atherosclerosis were studied. The observation
      period made up 4 weeks. The patients were divided into two groups. Group I-
      experimental group (50 patients) and group II-control group (16 patients) The
      patients of both groups were given standard therapy, but the patients of group I
      were additionally given 200mg soybean flavonoid supplement (daily dose 100mg. in
      capsules two times a day after meals). Clinical observation showed that the
      patients had no adverse reactions due to intake of the natural food supplement.
      Compared to the control patients better dynamics of clinical signs was observed
      in experimental group: reduction of chest pain intensity, arrhythmia and
      breathlessness, increase of tolerance to physical load, manifested of
      normalisation arterial hypertension and reduction of heart rate. Biochemical
      analysis showed an antiatherogenic and hypolipidemic effect of the soybean
      flavonoid supplement. Statistically reliable increase of NO; reduction of general
      peripherial vascular resistance and improvement of systolic function. Therefore
      it can be concluded that given biologically active supplement can be used in the
      treatment of atherosclerosis as an effective therapeutic tool.

PMID- 17179586
TI  - [Basal ganglia calcification: clinical manifestations and diagnostic evaluation].
AB  - Physiological intracranial calcification occurs in about 0,3-1,5% of cases. It is
      asymptomatic and is detected incidentally by neuroimaging. Pathological basal
      ganglia calcification is due to various causes, such as: metabolic disorders,
      infectious and genetic diseases and other. Hypoparathyroidism and
      pseudohypoparathyroidism are the most common causes of pathological basal ganglia
      calcification. Besides tetany and seizures this condition is presented by
      parkinsonism and dementia. Such parkinsonism doesn't respond to drugs containing
      levodopha. Infections (toxoplasmosis, rubella, cytomegalovirus, cysticercosis,
      AIDS) give multiple and asymmetric intracranial calcification. Inherited and
      neurodegenerative diseases cause symmetrical, bilateral basal ganglia
      calcification which is not related to metabolic disorders (blood calcium level
      and other), those are: Cockayne syndrome, tuberous sclerosis, Fahr's syndrome,
      Down syndrome and other. We observed some cases of basal ganglia calcification
      and studied clinical manifestations and treatment tolerance of this pathological
      condition. Since adequate treatment of hypoparathyroidism may lead to marked
      clinical improvement, serum concentration of calcium, phosphorus, and
      parathyreoid hormone is suggested to be determined in all individuals with
      calcification of the basal ganglia to rule out hypoparathyroidism. Basal ganglia
      calcification in young patient with acute hepatitis may be result of Wilson
      disease.

PMID- 17179587
TI  - [The role of oxidative stress in pathogenesis of GBS].
AB  - Axon degeneration accompanying its demielinization is a main course of
      neurological insufficiency typical for GBS. The mechanisms of axon degeneration,
      considered as the secondary result of serve inflammation are not established. We
      aimed to determine the role of oxidative metabolism in viral polyneuropathy
      pathogenesis. The activity of pro- and antioxidant systems of the body was
      studied by electron paramagnetic resonance (EPR) method. In blood and
      cerebrospinal fluid the intensive EPR signals of nitric oxide (NO), complexes of
      NO with nonhemic iron (HbNO), lypo- and superoxide radicals content noticeably
      increases, the signals of free Mn2+ and Fe2+ revealed, the activity of blood
      antioxidant enzymes, ceruloplasmin and katalasa increases (by 60%),
      superoxidedismitase's and glutation reductases activity decreases (by 20% and 70%
      correspondingly). It was considered, that inflammatory damage of nervous system
      induced by different infectious stimulus is initiated by activated immune cell
      proinflamatory agents (reactive oxygen and nitrogen species). Subsequently the
      oxidative stress, as result of accumulation of generators of reactive oxygen
      species, disordered intracellular metabolism products, contributes to axon
      demielinization and degeneration.

PMID- 17179588
TI  - [Colorimetric determination of eccrine sudoriferous glands functional condition
      in case of hyperhidrosis and their correction by belladonna].
AB  - For study of the sweat secretion in 27 patients suffered by local hyperhidrosis
      method of colorimetric determination of functioning sudoriferous glands number
      and a Minor's tests were used. The confines and intensity of sweat secretion have
      been determined. Study was carried out before and during the treatment as well as
      at the moment of clinical recovery. Revealing of vegetative syndromes was
      provided by Vein's inquirer. In patients with hyperhidrosis vegetative
      abnormalities were combined with asthenic disorders. Duration of illness had
      impact on frequency and character of neurasthenic syndrome manifestation. Offered
      scheme of local hyperhidrosis treatment with staged use of belladonna and
      antihistaminic preparation "hydroxyzine" (having antimuscarinic action) could be
      characterized as a well endurable and significantly ameliorative of patient's
      clinical status.

PMID- 17179589
TI  - Growth hormone (GH) determinations by RIA and IFA during GH stimulation tests in
      children with short stature.
AB  - Growth hormone deficiency (GHD) as a syndrome comprises multiple pathogenetically
      distinct entities caused by disorders of secretion or peripherial action of
      growth hormone (GH). Confirmation of the diagnosis of GH deficiency in children
      is based on provocative testing for human growth hormone (hGH). Immunofunctional
      assay (IFA) allows quantitation of only biological active GH forms in
      circulation. The aim of this study was to compare the results of GH
      determinations by radioimmunoassay (RIA) and IFA, and to establish cut-off-levels
      for IFA in insulin tolerance test (ITT). We have investigated 32 children (30
      males and 2 females) with short stature. All patients underwent insulin tolerance
      test (ITT), GH was measured in duplicate by radioimmunoassay (RIA, Seria) and IFA
      (DSL). Children with peak GH concentration below 10 ng/ml in ITT (by RIA)
      underwent arginin tolerance test (ATT, arginin 0,5 g/kg). The correlation between
      the results of growth hormone determination by radioimmunoassay and
      immunofunctional assay was excellent and cut-off-level in stimulatory test was
      established for the immunofunctional assay.

PMID- 17179590
TI  - Inhibitors of the kinin system as an alternative method of prevention or
      reduction reperfusive damages within thrombolytic therapy in patients with acute
      myocardium infarction.
AB  - The aim is to show the effectiveness of inhibitors of the kallikrein-kinin system
      (KKS) to avoid early microcirculation impairment and low reperfusion damages in
      the ischemic area during systemic thrombolysis (T) in order to achieve optimal
      results of thrombolytic therapy (TLT) in patients with acute myocardium
      infarction. Patients (n=104) with acute myocardium infarction were divided into 4
      groups: treatment with early TLT infusing Contrycal (Aprotinin) and Heparin (CH)
      during the first 2 hrs from the onset of disease (Gr. 1); treatment for isolated
      T at an early stage (Gr. 2); TLT with late T (in 3-6 hrs) (Gr. 3); and
      conventional therapy (Gr. 4). The dynamics of clinical and ECG data were
      evaluated for each of the groups. Before the clinical study was fully evaluated,
      an experimental-morphological, controlled study was carried out on dogs. These
      results showed improved retrograde blood flow of the acute ischemized myocardium
      and decrease in ischemia level, together with reduction of frequency and area of
      reperfused intramiocardial haemorrhages (RPIMH) in infarction areas under the TLT
      and CH infusion. When CH was infused a significant advantage was revealed in
      early T that showed high antianginal and antiarrhythmic effect, while no Q wave
      was observed or it was deepened non-significantly. More clinical dynamic problems
      with extrasystols and significant deepening of Q wave were seen in the earlier
      isolated T (Gr. 2) that were worse than those seen in Gr. 1 conditions, but the
      problems were more negative in the patients from Gr. 3 and 4. CH optimizes the
      situation causing suppression of the pathological activation of KKS, decreasing
      vessel permeability, and reducing reperfusion damage. The latest thrombolytic
      drugs ensure faster thromb lysing but do not prevent the reperfusion damage, as
      higher fibrinolytic activity at the moment of T causes enhanced activation of KKS
      and RPIMH development and prevents peroxide oxidation of the lipids but this may
      result in higher affectivity of antioxidant use. Earlier administration of KKS
      inhibitors optimizes the affectivity of TLT and widens the indication to the
      systemic and intracoronary T, minimizes complications, and may cause higher
      affectivity of coronary angioplasty (CAP) and aorta-coronary shunting in patients
      with acute myocardium infarction.

PMID- 17179591
TI  - Effectiveness of needle/syringe exchange program in Tbilisi.
AB  - IDUs are under the high risk of HIV and other blood born diseases. In Georgia
      injecting drug use is associated with two third of registered HIV/AIDS cases.
      Majority of them are also infected with B and C Hepatitis. One of the main
      components of HIV/AIDS prevention among drug users is considered to be harm
      reduction programs, among them syringe exchange program. We conducted
      observational cohort study and performed interviewing participants of syringe
      exchange program using structured questionnaire. The interviewing was conducted
      at intake, after 3 months and at the end of the program. During interviewing we
      used risk assessment questionnaire which we have little adapted (Risk Assessment
      Battery, Navaline, et al, 1994). The data were statistically analysed using SPPS
      11, 5 program. The aim of the study was to assess the efficacy of outreach and
      needle exchange programs in terms of reduction of HIV risk behavior of injection
      drug users in Tbilisi. The results of the study show visible reduction in
      injection risk behavior for clients being in the program for at least three
      months. There was not seen any significant change in the level of sexual risk
      behavior, which might suggest the need for targeting this behavior during the
      further interventions. The results of the study suggest a visible potential
      benefit to drug users and communities that could be gained through the wide scale
      implementation of harm reduction programs in Georgia.

PMID- 17179592
TI  - Parameters of oxidative metabolism in neonates suffering from sepsis and anemia.
AB  - Neonatal sepsis still remains as one of the actual problems in modern medicine
      due to its high morbidity and mortality rates determined by diagnostic
      difficulties and absence of sufficient evidence for effective therapy. Literature
      data have shown that essential role in pathogenesis of sepsis belongs to the
      cellular oxidation-reduction misballance and development of the oxidative stress.
      The aim of our work was to assess indices of pro- and antioxidant systems in term
      neonates with sepsis on the background of anemia and without it. A total of 41
      neonates (17 male, 24 female) with the age range from 3 to 7 days, with early
      sepsis, and in 2003-2005 years treated at the department of neonates' therapy and
      intensive care unit of pediatric clinics of the Tbilisi State Medical University
      were under observation. The control group involved 17 practically healthy
      neonates of the same age range. In consequence of the analyses there was
      ascertained, that with anemia increases intensification free-radical oxidation
      process. At the same time, antioxidant system activity was not change
      significantly in the sepsis with anemia, than other one. Pathogenesis of anemia
      may was founded undergo hemolitic anemia results by oxidative stress. According
      to the results of investigations could be concluded that in case of anemia
      developed at neonatal sepsis supports intensify of oxidative stress and at the
      same time anemia is the result of the oxidative stress.

PMID- 17179593
TI  - [Influence of ecological factors on the frequency of respiratory diseases in
      children in the zone of oil catastrophe].
AB  - In the village Ninotsminda, district of Sagarejo, the important environmental
      contamination was provoked by the explosion of oil bore-hole. Intoxication of the
      children' s respiratory system with the oil-associated gases was studied. 420
      children, residing at the contaminated district of Ninotsminda and 50 children,
      residing at the nearby ecologically clear village Badiauri (in the distance of 6
      km) were investigated. The observations were done quarterly and included clinical
      laboratory investigations. As a result of the study it was shown that the
      frequency of different diseases was increased sharply among the children from the
      in catastrophe zone in comparison with the control zone, diseases of upper
      respiratory system dominated in the nozological structures of diseases.

PMID- 17179594
TI  - A new method of standartization of health-promoting pomegranate fruit (Punica
      granatum) extract.
AB  - This study analyzes the major phenolic constituents of pomegranate fruit juice
      and pericarp feedstock, and dry extracts thereof, using high-performance liquid
      chromatography. Pomegranate pericarp was extracted with water (WE) and alcohol
      (AE) as solvents, and liquid extracts were subsequently freeze-dried. The results
      indicate that ellagitannins punicalagin A and punicalagin B are the major
      constituents in the primary pomegranate feedstock and in both types of extracts.
      Ellagic acid, a common botanical constituent that is currently used to
      standardize pomegranate extracts, as well as ellagitannin punicalin, were found
      to be only minor constituents. Total punicalagins (the sum of punicalagins A+B
      and punicalin) and ellagic acid content in the pomegranate fruit pericarp
      feedstock WE were 7,6+/-0,3% and 0,2+/-0,1% by dry weight, respectively, and in
      the AE feedstock 7,0+/-0,2 and 0,4+/-0,1%, respectively. Total phenolic content
      (the sum of punicalagins and ellagic acid) in the pomegranate WE and AE were
      45,8+/-1,2% and 42,3+/-1,1%, respectively. The concentrations of ellagic acid in
      the pomegranate WE and AE were 0,8+/-0,2% and 3,9+/-0,2%, respectively. Total
      phenolics in fresh single-strength pomegranate whole fruit juice contained
      2,216+/-70 mg/L (95% punicalagins), whereas commercial pomegranate juice that was
      purchased from local stores was 317+/-13 mg/L (70% punicalagins). Our results
      strongly suggest that the commercially produced pomegranate extracts should be
      standardized to the content of total punicalagins as well as ellagic acid. The
      current standard uses only ellagic acid, which is unreliable, potentially
      misleading and vulnerable to commercial adulteration.

PMID- 17179595
TI  - Efficiency of pharmacologically-active antioxidant phytomedicine Radical Fruits
      in treatment hypercholesteremia at men.
AB  - The purpose of this randomized, double-blind, placebo controlled intervention
      clinical trial was to investigate the effect of orally administered dietary
      supplement Radical Fruits (www.gardenoflife.com) consisting of highly
      concentrated edible fruits and berries on the concentration of plasma
      cholesterol, urinary 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) and 11
      dehydrothromboxane B2 (11-dehydro-TXB2) in none-obese, non-smoking, non-diabetic
      hypercholesteremic male volunteers. Forty four (n=44) none-obese, non-smoking,
      non-diabetic male volunteers with an average age of 40+/-12 years, average body
      weight of 77,4+/-5,0 kg, average body mass index (BMI) of 22,2+/-2,7 kg/m2 and
      average total plasma cholesterol level 280+/-22 mg/dL were recruited to take part
      in a 4 week double-blind, randomized, placebo-controlled clinical trial. After
      evaluating 12 different antioxidant supplements for their phytochemical
      compositions and bioavailability, a dietary supplement Radical Fruits was chosen
      for this clinical trial. Radical Fruits contains standardized extracts and
      concentrates of prune, pomegranate, apple, grape, raspberry, blueberry, white
      cherry and strawberry. Subjects were randomly assigned to the treatment group and
      the placebo group using Simple Randomization Procedure. Subjects in the treatment
      group (n=22) were directed to take 900 mg of Radical Fruits supplement three
      times a day before meals. Subjects in the control group (n=22) were directed to
      take placebo according to the same schedule. Food record analysis, body
      composition, blood and urine samples were assessed on admission and then once a
      week. The duration of the clinical trial was 4 weeks. Administration of Radical
      Fruits(TM) for 4 weeks resulted in statistically significant reduction of total
      plasma cholesterol from 280+/-23 to 250+/-11 mg/dL, (p<0,001). Total plasma
      cholesterol changes in the placebo group were not statistically significant. The
      average plasma LDL was reduced from 195+/-23 to 169+/-21 mg/dL (p<0,001) in the
      Radical Fruits(TM) group, while in the placebo group there were no statistically
      significant changes. Plasma HDL increased by 3,2=/-0,6% in the Radical Fruits
      treated group (p<0,001). No significant changes in the HDL levels were observed
      in the placebo group. Urinary 8-epi-PGF2alpha level decreased from 450+/-170 to
      330+/-159 pg/mg creatinine (p<0,001); urinary 11-dehydro-TXB2 level decreased
      from 1,200+/-420 to 790+/-320 pg/mg creatinine (p<0,001) with no changes in the
      placebo group. Administration of pharmacologically active antioxidant supplement
      Radical Fruit(TM) in hypercholesteremic men significantly increased plasma HDL
      and reduced total cholesterol and LDL, and urinary oxidative and inflammatory
      isoprostanes and thromboxane.

PMID- 17179596
TI  - [Healing activity of the oil extract of tea leaf].
AB  - At the department of organic chemistry and chemical technology oil extraction of
      tea leaf has been received (conditionally EM ChL). Pharmacological action of the
      medicine EM ChL has been studied on the models of linear and plane wounds,
      thermal and chemical burns of a skin in white rats. As a drug of comparison Aekol
      has been used in the comparable doses according to the recommendations of
      pharmacological committee (registration number 87/295/3). Effect of drug EM ChL
      on the consolidation of wound scar was studied in the purebred white male with
      the weight range of 120-140 gr. For tensiometry the device adapted for
      determination of the module of elasticity of gum BH-5307 has been used. Using the
      model of linear wound, stimulating effect of the preparation EM ChL on the
      healing process has been shown using tensiometry and hystological data. The
      preparation accelerates the healing process of the wound.

PMID- 17179597
TI  - [Effects of ultracaine on the local blood flow of the gum and on the development
      of cerebral seizures in experiment].
AB  - We have studied the effect of ultracaine DS forte on local blood flow of the rat
      gum as well as on the development of the convulsion activity of the brain at
      systemic injection. Experiments were carried out on 12 mongrel albino mail rats
      of 200-250 g weight. In the I group of animals under the light chloral hydrate
      anesthesia we studied the changes of local blood flow in the rat gum of lower jaw
      after ultracaine DS forte injection (right side) and the similar quantity of
      phisiological solution (left side). According to our data, in the right gum, the
      rate of local blood flow decreases statistically significantly at 18%, while the
      injection of physiological solution did not result in any changes. In the II
      group, experiments were carried out on the animals with bipolar electrodes in
      neocortex, as well as in the right and the left dorsal hippocampus. On the fifth
      day after surgical intervention, on the background of registration of electric
      activity of the above stated structures 0,03-0,04 ml of ultracaine Ds forte was
      injected intraperitoneally, which did not result in any significant deviation on
      the encephalogram. 10-fold doze injection was followed by abortion of epileptic
      discharges (0,3 ml), but repeated injection of 0,3 ml of preparation resulted in
      generalized clone-tonus type seizure activity. Simultaneously, clone-tonus type
      behavioral manifestation was revealed.

PMID- 17179598
TI  - [Influence of the chronic exposure to network frequency electromagnetic field on
      rats under interrupted and continuous action of EMF].
AB  - The aim of the study was the investigation of chronic exposure to network
      frequency electromagnetic field in the rats under interrupted or continuous
      action of electric magnetic field. We were studying their behavior by the method
      of "open field". Comparison of behavior of rats in the "open field" has shown
      that the significant difference in the emotional activity of rats was stated. The
      number of boluses and urination in rats of B group is 4,5 times more than in the
      individuals of C group (p<0,001), but the significant difference between the rats
      of control A and B groups has not been stated. Although, the number of boluses in
      the rats of B group was a little raised, this raise was not statistically
      significant (p<0,5). The rats of control A and C groups significantly
      distinguished from one another. The number of boluses and urination in the
      animals of C group was significantly lower (p<0,001). In that way, the rats which
      were under the discontinuous action of electromagnetic field were distinguished
      by high emotionality, which occur by increase of boluses and urination, the high
      number grooming behavior and increase of the number of translocation, that
      influences the functioning of hypothalamohypophysial system.

PMID- 17179599
TI  - [Revealing of the role of NO in the pathogenesis of hypothyroidism].
AB  - There have been studied changes in blood and tissue NO levels and its correction
      in rats exposed to thyrectomy. NO levels were measured by the method of EPR using
      spin-trap sodium diethyldithiocarbamat. In 22 hours after thyrectomy contents of
      free nitric oxide in myocardium and liver tissues increased by 33% and 43,3%
      respectively. At the same time, intensive EPR signals of nitrosyl complexes of
      non-heme iron (FeSNO, g=2,03) were registered in EPR spectra of liver and
      myocardium tissues, at that free nitric oxide levels in blood of animals
      significantly decreased. In conclusion, NO-dependent signal system plays
      important role in the regulation of redox-homeostasis at hypothyroidism; long
      term inadequate activation of NO synthesis may cause intensification of body
      oxidative stress, which in turn results in oxidative degradation of vasoactive
      nitric oxide, disturbance of blood vessel reactivity, alteration of tissue blood
      and oxygen supply, that in turn facilitate farther aggravation of oxidative
      metabolism disorder and the development of irreversible alterations in tissues.
      In case of treatment with L-thyroxin or L-thyroxin + oligocrin oxidative
      metabolism markers and content of NO in blood and tissues normalize, at that
      oligocrin enhances thyroxin efficacy. Thus, based on the obtained results of the
      conducted research we suggest that application of pharmaceutical preparations
      with antioxidant activity along with specific hormonal therapy is appropriate for
      treatment of hypothyroidism.

PMID- 17179600
TI  - [Peculiarities of ion transport of calcium in tumor cells under conditions of
      irradiation by ionizing radiation, chemopreparations and homeopathic means].
AB  - The goal of given investigation was to reveal an effect of different agents on
      ion transport of Ca2+ in tumor cells (Erlich's carcinomas). Ionizing radiation,
      antitumor preparation vinkristin as well as homeopathic means - stimulated
      phosphoric acid diluted at 10-14 were used. Small doses of radiation (0,05 and
      0,1 Gr) always had a stimulating effect on ion transport even in combination with
      vinkristin, which separately always depressed it. Both separately and in any
      combination stimulated phosphoric acid always reinforced transmembrane ion
      transport. In regard to Ca2+ a hypothesis about its participation in the process
      of reparation of tumor cell has been suggested. At increasing of Ca2+
      concentrations a transmembrane transport of this ion in the environment increases
      what induces strengthening of adhesive properties of the cell. However, it is
      known that in tumors these properties are decreased. Apparently, in this case two
      contrary processes - strengthening and decrease of adhesive properties take place
      pointing to the fact that there appear reparative forces in tumor process.

PMID- 17179601
TI  - [Analysis of the situation of some urgent surgical services during the reform
      period in health care system in Adjara].
AB  - The reform that started in 1995 in health care system still is in progress in our
      country. It is necessary to evaluate the advantages and disadvantages of past
      period in order to achieving the objectives. For this aim we used the statistical
      facts gathered during the reforms and according to those data we tried to analyse
      the existing situation of urgent surgical service. We describe the main problems
      that would be the best way to solve them in the future. The results show that the
      urgent surgical help in a hospital still has enough reserve for optimization and
      reorganization, but it is clear, that for field working improvement there is
      necessity of the appropriate reformation of institutional organization,
      financing, program maintaining and human resources.

PMID- 17179602
TI  - A symmetrical indexing scheme for decagonal quasicrystals analogous to Miller
      Bravais indexing of hexagonal crystals.
AB  - The problems of redundancy and superfluous indices in indexing the planes and
      axes in a decagonal quasicrystal are considered, using a scheme of five coplanar
      vectors in the quasiperiodic plane and one perpendicular vector. Of all the
      indexing schemes in use, this scheme offers the maximum advantage. An analogy is
      drawn to the hexagonal system using Miller-Bravais indices. Based on this, a
      symmetry-based indexing system for decagonal phases is devised that follows a
      simplified approximate zone law analogous to the exact zone law for the hexagonal
      case. The indices based on this scheme will be designated as ;Frank indices'.
      High-symmetry electron diffraction zone-axis patterns as well as powder X-ray
      diffraction patterns are indexed using Frank indices and compared with those of
      other indexing schemes.

PMID- 17179603
TI  - Multiple twinning in cubic crystals: geometric/algebraic study and its
      application for the identification of the Sigma3(n) grain boundaries.
AB  - Multiple twinning in cubic crystals is represented geometrically by a three
      dimensional fractal and algebraically by a groupoid. In this groupoid, the
      variant crystals are the objects, the misorientations between the variants are
      the operations, and the Sigma3(n) operators are the different types of operations
      (expressed by sets of equivalent operations). A general formula gives the number
      of variants and the number of Sigma3(n) operators for any twinning order.
      Different substructures of this groupoid (free group, semigroup) can be
      equivalently introduced to encode the operations with strings. For any coding
      substructure, the operators are expressed by sets of equivalent strings. The
      composition of two operators is determined without any matrix calculation by
      string concatenations. It is multivalued due to the groupoid structure. The
      composition table of the operators is used to identify the Sigma3(n) grain
      boundaries and to reconstruct the twin related domains in the electron back
      scattered diffraction maps.

PMID- 17179604
TI  - Simultaneous fitting of X-ray and neutron diffuse scattering data.
AB  - Conventional crystallographic refinement uses the Bragg-peak intensities and
      gives the single-site average crystal structure. Information about short-range
      order and local order is contained in the diffuse scattering that is distributed
      throughout reciprocal space. Models of the short-range order in materials can now
      be automatically refined. The complementarity of X-ray and neutron diffraction
      data, and the value of simultaneously refining a structural model against both
      types of data, has long been known. This paper presents the first refinement of a
      short-range-order model against comprehensive X-ray and neutron diffuse
      scattering data simultaneously. The sample is the organic molecular crystal
      benzil, C(14)H(10)O(2) (for neutron work H is replaced by D). The technique gives
      new insights into local order in crystalline materials, including the dynamic
      correlation structure indicative of the dynamics of molecules in the crystalline
      state, and successfully overcomes limitations of using only the X-ray data set.

PMID- 17179605
TI  - Effectiveness of iterative algorithms in recovering phase in the presence of
      noise.
AB  - Inversion of coherent X-ray diffraction patterns allows the imaging of three
      dimensional density distributions. The recovery of such shapes often requires
      application of iterative algorithms, such as Fienup's error reduction or hybrid
      input/output. Since the measurement of such a pattern records the intensity in
      reciprocal space, any errors due to noise will probably not have a
      straightforward impact on the final real-space result. In this paper, the effect
      of the types of noise common in coherent X-ray diffraction (CXD) experiments,
      counting statistics, scatter from alien particles and detector noise, on the
      recovered real-space density projection is explored by simulating a two
      dimensional CXD pattern and adding noise. It is found that an R factor measuring
      the reproducibility between the best and second-best real-space result is a
      leading indicator of performance.

PMID- 17179606
TI  - Accurate structure factors and experimental charge densities from synchrotron X
      ray powder diffraction data at SPring-8.
AB  - Accurate structure factors of silicon and diamond have been experimentally
      determined from powder diffraction data measured at the third-generation
      synchrotron-radiation source SPring-8, BL02B2. The accuracy of the obtained
      structure factors has been evaluated by comparing with structure factors in the
      literature measured by the Pendellosung method and with some from theoretical
      calculations. The results indicate that the structure factors from powder data
      are accurate enough to discuss the experimental charge-density distributions of
      these materials. The number of structure factors of silicon determined in the
      present study is 104, which is three times more than that of previous
      Pendellosung data. The experimental charge densities have been obtained by the
      maximum-entropy method from the present structure factors. The charge densities
      at bond mid-points for silicon and diamond show good agreement with different
      kinds of theoretical calculations. The present study proved that the powder
      diffraction at SPring-8 is a promising method for determination of experimental
      charge density for a wider range of materials.

PMID- 17179607
TI  - Infinite geodesic paths and fibers, new topological invariants in periodic
      graphs.
AB  - Rings are well known invariants of nets. In this work, a generalization of the
      concepts of cycles and rings is introduced. Infinite paths in periodic graphs are
      defined as connected, acyclic, regular subgraphs of degree two; geodesics are
      defined as infinite paths such that the unique path between any pair of vertices
      is a geodesic path in the whole graph. An infinite path can be thought of as an
      infinite cycle and a geodesic as an infinite ring. In a further step, a geodesic
      fiber is defined as a minimal 1-periodic subgraph that contains all geodesic
      paths between any pair of its vertices. Geodesic fibers are topological
      invariants of periodic graphs whose labeled quotient graphs are subgraphs of the
      labeled quotient graph of the whole graph; the paper describes applications of
      geodesic fibers to the analysis of the automorphisms of minimal nets,
      crystallographic and non-crystallographic nets.

PMID- 17179608
TI  - Direct Bragg-peak phase retrieval by a hybrid-input-output algorithm with proper
      intensity normalization.
AB  - A hybrid-input-output algorithm is applied to reconstruct hypothetical carbon
      cluster crystals in both two and three dimensions. It is shown that normalizing
      the Bragg peaks to those from a cluster of solid spheres or discs with uniform
      electron density can often lead to faithfully reconstructed objects at both
      atomic and low resolutions. It is shown that, even without the central peak, low
      resolution structures can still be reconstructed with good fidelity. The effect
      of Bragg-peak noise on object reconstruction is examined throughout the paper.
      Successful reconstructions of 500- and 1000-atom carbon cluster crystal
      structures at both atomic and low resolutions are given.

PMID- 17179609
TI  - Transformational space-group symbols.
AB  - Ambiguities present in space-group construction from the Hermann-Mauguin (H-M)
      symbols enforce the use of other space-group designations or H-M symbol
      modifications. Therefore, a transformational space-group symbol (TSG) composed of
      the well defined standard space-group identifier, an axis-system transformation
      and origin shift is proposed as a symbol of any space-group description. The
      first description given in International Tables for Crystallography [(1983), Vol.
      A, Space-Group Symmetry, edited by Th. Hahn. Dordrecht: Reidel (ITA83)] or the
      second one for space groups with two origins is suggested here as a reference
      description. For standard descriptions based on the ITA generators and compiled
      list of the TSG symbols, all conventional space-group settings listed in ITA83
      can be reconstructed.

PMID- 17179612
TI  - Antiretroviral therapy: need for a long-term view.

PMID- 17179613
TI  - Prurigo pigmentosa: an underdiagnosed disease?
AB  - Prurigo pigmentosa is a distinctive inflammatory disease first described by the
      Japanese dermatologist Masaji Nagashima in 1971. It is typified by recurrent,
      pruritic erythematous macules, papules and papulovesicles that resolve leaving
      behind netlike pigmentation. The disease is rarely diagnosed outside Japan,
      because clinicians outside Japan are not well conversant with the criteria for
      its diagnosis. Only one patient from India has been published previously under
      the diagnosis of prurigo pigmentosa, a hint that the disease may be under
      recognized in India. We present an account of our observations in patients
      diagnosed with prurigo pigmentosa who were of five different nationalities,
      namely, Japanese, German, Indonesian, Turkish and Iranian. With this article we
      seek to increase awareness for the condition among dermatologists in India and we
      provide criteria for its diagnosis, both clinically and histopathologically.

PMID- 17179614
TI  - Immune reconstitution inflammatory syndrome.

PMID- 17179615
TI  - Profile of systemic sclerosis in a tertiary care center in North India.
AB  - AIM: To study the clinical and immunological profile in patients of systemic
      sclerosis from North India and compare it with other ethnic groups. METHODS:
      Patients presenting to us between the years 2001 and 2004 and fulfilling the
      American Rheumatism Association (ARA) criteria for systemic sclerosis were
      included. There were 84 females and 16 males with the mean age of 32.5 +/-11.62
      years and a mean duration of 6.49 +/- 4.34 years. All patients were admitted to
      the dermatology ward for detailed history and examination including Rodnan score.
      Investigations including hemogram, hepatic and renal functions, serum
      electrolytes, urine for albumin, sugar, microscopy and 24h urinary protein
      estimation, antinuclear antibody, chest X-ray, barium swallow, pulmonary function
      test, electrocardiogram and skin biopsy were done. RESULTS: The most common
      presenting symptoms were skin binding-down (98.5%), Raynaud's phenomenon 92.9%,
      pigmentary changes 91%, contracture of fingers 64.6%, fingertip ulcer 58.6%,
      restriction of mouth opening 55.5%, dyspnea 51.1%, joint complaints 36.7% and
      dysphagia in 35.2%. The mean Rodnan score was 25.81 +/- 10.04 and the mean mouth
      opening was 24.6 +/- 19.01 mm. The laboratory abnormalities included raised ESR
      in 87.8%, ANA positive in 89.1%, proteinuria in 6.0%, abnormal chest X-ray in
      65.3%, abnormal barium swallow in 70.2% and reduced pulmonary function test in
      85.8%. CONCLUSION: The clinical and immunological profile of systemic sclerosis
      in North India is similar to that of other ethnic groups except that pigmentary
      changes are commoner and renal involvement is relatively uncommon.

PMID- 17179616
TI  - Study of upper gastrointestinal tract involvement in pemphigus by esophago-gastro
      duodenoscopy.
AB  - INTRODUCTION: Involvement of upper gastrointestinal tract in pemphigus vulgaris
      is not uncommon. AIM: To study the involvement of upper gastrointestinal tract
      (UGIT) with the help of esophago-gastro-duodenoscopy (EGD) in patients of
      vesiculobullous dermatoses with emphasis on pemphigus vulgaris. METHODS: Forty
      two patients (M-22, F-20) with vesiculobullous dermatoses, diagnosed on the basis
      of clinical features and skin histopathology as pemphigus vulgaris (PV)-40
      patients and pemphigus foliaceus (PF)-2 patients were included in the study. The
      EGD was performed and mucosa of the esophagus, stomach and first part of the
      duodenum were examined. Mucosal biopsies were taken from the lower esophagus in
      26 patients of PV and studied after H and E staining. RESULTS: On EGD, esophageal
      involvement was seen in 67% patients of PV (27/40). Of these, Grade I esophagitis
      was observed in seven, Grade II in 11, Grade III in four and Grade IV involvement
      was seen in five patients of PV. Three PV patients had associated esophageal
      candidiasis. Involvement of esophageal mucosa was also observed in one out of two
      patients of PF. Gastric mucosa was involved in 52% and duodenal mucosa in 20% of
      PV patients. Acantholysis was observed in seven out of 26 (27%) esophageal
      biopsies of PV patients. Two patients of PV vomited a tube-like structure,
      indicative of 'esophagitis dissecans superficialis'. The involvement of the
      gastric mucosa in patients with history of oral corticosteroid intake (60%) was
      compared to the group without history of oral corticosteroids (30%). CONCLUSION:
      Among PV patients under study, significant involvement of oral (87%), esophageal
      (67%), gastric (52%) and duodenal mucosa (20%) was observed.

PMID- 17179617
TI  - Men who have sex with men and transgenders in Mumbai, India: an emerging risk
      group for STIs and HIV.
AB  - BACKGROUND: Men who have sex with men and transgenders are an important risk
      group for sexually transmitted infections (STIs) and human immunodeficiency virus
      (HIV). They have risky sexual behaviors but low risk perception. OBJECTIVES: To
      assess the sexual behavior, STIs, HIV and identify factors associated with HIV in
      men who have sex with men (MSM) and transgenders (TGs) in Mumbai. METHODS:
      Participants were enrolled from two clinics in Mumbai. They completed an
      interviewer-administered questionnaire and were evaluated for STIs and HIV
      infection. RESULTS: A total of 150 participants, 122 MSM and 28 TGs were
      evaluated; 17% of MSM and 68% of the TGs were HIV infected. HIV infection in MSM
      was associated with serological positivity for HSV2 IgG [adjusted odds ratio
      (aOR), 95% confidence interval (CI): 9.0 (2.2-36.9)], a positive Treponema
      pallidum hemagglutination assay (TPHA) [aOR (95% CI): 6.0 (1.5-24.0)], greater
      than five acts of receptive anal sex in the past six months [aOR (95% CI): 4.3
      (1.2-15.0)] and per category increase in age (18-24 yrs, 25-29 yrs, > 30 yrs)
      [aOR (95% CI): 3.1 (1.3-7.1)] in multivariate analysis. Consistent condom use
      during receptive anal sex in the past six months was low (27%). Many MSM were
      married (22%) or had sex with females and may act as a 'bridge population'. HIV
      infection in TGs was associated with a positive TPHA [OR (95% CI): 9.8 (1.5
      63.9)] and HSV 2 IgG [OR (95% CI): 6.7 (1.1-40.4)] in univariate analysis.
      CONCLUSION: Prior STIs were strongly associated with HIV infection in MSM and
      TGs. These groups should be the focus of intensive intervention programs aimed at
      STI screening and treatment, reduction of risky sexual behavior and promotion of
      HIV counseling and testing.

PMID- 17179618
TI  - Preparation and evaluation of cosmetic patches containing lactic and glycolic
      acids.
AB  - BACKGROUND: Alpha-hydroxy acids such as glycolic acid (GA) and lactic acid (LA),
      are used in cosmetic patches. The important fact in cosmetic patches is its
      suitable adhesion and peel properties. AIM: The objective of this study was to
      prepare LA- and GA-containing cosmetic patches and evaluate in-vitro/in-vivo
      correlation of adhesion properties. METHODS: Pressure-sensitive adhesives with
      different concentrations of GA and LA were cast on a polyethylene terephthalate
      film. The patches were evaluated for peel adhesive strength. On the basis of in
      vitro adhesion properties the patches were selected for wear performance tests
      and skin irritation potential. RESULTS: The adhesion properties (adhesion to
      steel plate and skin) and cohesive strength tests indicated the substantial
      influence of GA and LA concentrations. Based on in vitro adhesion studies the
      patches containing 3% (w/w) GA were selected for in vivo studies. In vivo studies
      show that a formulation containing 3% GA displays good adhesion on the skin, but
      it leaves little residues on the skin. Skin Irritation studies on healthy human
      volunteers showed negligible erythema at the site of application after 48 h.
      CONCLUSION: The noninvasive patch test model was found useful for detecting
      irritant skin reactions to the cosmetic patch containing GA. Our results
      demonstrated a strong correlation between the adhesion to steel plate and
      adhesion to skin. But a weak correlation between the degree of adhesive residue
      on the skin in in vitro and in vivo tests was observed for the formulation
      containing 3% (w/w) GA.

PMID- 17179619
TI  - Cutaneous vasculitis as a presenting feature of multiple myeloma: a report of 2
      cases.
AB  - We report two male patients who presented with symmetrical, painful purpura that
      evolved into bullae and necrotic ulcers, predominantly on the extremities, over
      two months in spite of conventional therapy including oral steroids. Examination
      showed livedoid and purpuric patches with necrotic centers in starburst pattern
      over the extremities and buttocks. The first case also had similar lesions over
      the ears. The clinical presentation and the histopathological examination
      suggested a diagnosis of necrotizing leukocytoclastic vasculitis (LCV). Blood
      testing ruled out connective tissue disease, hepatitis B or C infection or
      streptococcal infection as underlying cause of vasculitis. Serum antinuclear
      factor, antineutrophilic cytoplasmic antibody and anticardiolipin anticoagulant
      were negative in both cases. Cryoglobulins were positive in case 2. An incidental
      finding was raised serum proteins and globulins in case 2. Further investigations
      revealed M band on electrophoresis and features of multiple myeloma on bone
      marrow biopsy in both cases. These cases emphasize the importance of simple
      investigations like serum proteins in the evaluation of LCV.

PMID- 17179620
TI  - Bullous variant of acral erythema due to methotrexate.
AB  - Chemotherapy-induced acral erythema is a painful erythema of the palms and soles
      which occurs following chemotherapy. It is usually seen due to cytarabine,
      doxorubicin and fluorouracil. We present a 40-year-old male patient, a biopsy
      proven case of squamous cell carcinoma of the floor of the mouth, who developed a
      bullous variant of acral erythema after a single intravenous dose of
      methotrexate. He also had fever, buccal mucositis, leucopenia, thrombocytopenia
      and hyperpigmented macular rash on the face and upper trunk. The bullous variant
      of acral erythema due to methotrexate has rarely been reported.

PMID- 17179622
TI  - Epithelioid sarcoma: a diagnostic challenge.
AB  - Epithelioid sarcoma is an uncommon slow-growing soft tissue malignancy,
      associated with a high incidence of local recurrence and metastasis. We report a
      26-year-old male with epithelioid sarcoma on the right palm with a long history
      of over seven years, which was initially misdiagnosed as cutaneous tuberculosis
      and epithelioid hemangioendothelioma, as a result of which the treatment was
      delayed. No metastasis was found in our patient. The patient was referred to the
      oncology centre where he underwent wide excision of the lesion followed by
      radiotherapy. The review of the literature including clinical and histological
      differential diagnosis is presented as it mimics inflammatory, benign tumors as
      well as other malignant conditions.

PMID- 17179621
TI  - Lymphangitic chromoblastomycosis.
AB  - Chromoblastomycosis (CM), a chronic subcutaneous mycosis, is caused by several
      dematiaceous fungi, the most common being Fonsecaea pedrosoi. It usually occurs
      in the lower extremities following traumatic implantation of the organisms. We
      are reporting a case of chromoblastomycosis on the right lower limb in a
      sporotrichoid pattern caused by F. pedrosoi. The pattern was probably due to
      lymphatic spread that seems to be one of the rare presentations. The
      histopathology showed typical muriform or medlar bodies both intracellularly and
      extracellularly within the granuloma. Culture revealed sporulating organisms
      (Cladosporium and Rhinocladiella type) by a combination method, characteristic of
      F. pedrosoi. Our case responded well to itraconazole.

PMID- 17179623
TI  - Variant of Vohwinkel's syndrome.
AB  - A 28-year-old female born to consanguineous parents, presented with progressive
      palmoplantar keratoderma since the age of six months and a constricting band on
      right fourth finger of one year duration. There was history of similar complaints
      being present in two other family members. Associated clinical findings included
      starfish-shaped cornified plaques on knuckles, resorption of distal phalanges and
      keratotic plaques on elbows, groins and knees. The patient was mentally sound and
      had normal audiometry. Biopsy from hyperkeratotic plaque showed hyperkeratosis,
      parakeratosis, increased granular layer and papillomatosis. Gene mapping for
      loricrin mutation was found to be negative.

PMID- 17179624
TI  - Condom leukoderma.
AB  - Contact dermatitis from natural latex of condom has been reported and is
      attributed to latex sensitivity. Chemical leukoderma from rubber condom is
      probably not reported. Here we present a case of chemical leukoderma in a 32-year
      old male who developed depigmentation around the shaft of the penis in a
      circumferential pattern. Since the lesion was solitary and the site corresponded
      to the point of maximum contact of the condom, a diagnosis of contact leukoderma
      due to latex condom was thought of. Patch testing was done with
      mercaptobenzothiazole (MBT), dusting powder present in the condom and condom
      latex as such. The patient tested positive (3+) with mercaptobenzothiazole and
      the condom latex. On discontinuation of condom use and with UVB phototherapy,
      lesions repigmented in eight weeks.

PMID- 17179625
TI  - Alopecia universalis in Down syndrome: response to therapy.

PMID- 17179626
TI  - Dapsone-induced acute myopia.

PMID- 17179627
TI  - Dapsone-induced agranulocytosis in a patient of leprosy.

PMID- 17179628
TI  - Generalized pustular psoriasis of pregnancy treated with oral cyclosporin.

PMID- 17179629
TI  - Anti-aging therapies: other half of the story.

PMID- 17179630
TI  - Intradermal tests in dermatology-I: tests for infectious diseases.

PMID- 17179631
TI  - Imiquimod.

PMID- 17179632
TI  - Erythematous plaque over the face.

PMID- 17179633
TI  - A case of occupational bronchial asthma and contact dermatitis caused by ortho
      phthalaldehyde exposure in a medical worker.

PMID- 17179634
TI  - Human herpesvirus 6 reactivation in trichloroethylene-exposed workers suffering
      from generalized skin disorders accompanied by hepatic dysfunction.
AB  - Idiosyncratic generalized skin disorders resembling serious drug
      hypersensitivities have reportedly occurred after occupational exposure to
      trichloroethylene. However, factors associated with the disorders remain unknown
      except for trichloroethylene exposure. This study aimed at clarifying whether
      infectious diseases contributed to the development of rash or hepatitis in
      patients with trichloroethylene-related generalized skin disorders. Fifty-nine
      patients consecutively hospitalized between March 2002 and December 2003 and 59
      healthy exposed workers selected on an age-matched basis in the patients'
      factories were enrolled in the study. Information on possible risk factors for
      rash and hepatitis was collected with structured checklists. Antibody titers were
      measured for hepatitis A, B and C viruses, Mycoplasma pneumoniae, herpes simplex
      viruses 1 and 2, Epstein-Barr virus, cytomegalovirus, human herpesvirus 6,
      measles and rubella virus. Thirty-six cases (59%) showed exfoliative dermatitis,
      17 (28%) erythema multiforme, 4 (7%) Stevens-Johnson syndrome, and 4 (7%) toxic
      epidermal necrolysis. Before the onset of rash, 16 (27%) cases had received
      medication prescribed for the preceding fever, a main first symptom of the
      disorders. Marked increases in anti-human herpesvirus 6 IgG titer (> or =256),
      which indicated viral reactivation, were noted in 14 (25%) patients, while no
      abnormal increase was detected in the controls (p<0.001). Anti-measles IgM titer
      was positive in 2 (7%) cases but not in the controls (p=0.49). The involvement of
      other known risk factors of rash or hepatitis was ruled out. These results
      suggest that part of trichloroethylene-related generalized cutaneous disorders
      occurring in China and drug-induced hypersensitivity syndrome overlap in terms of
      human herpesvirus 6 reactivation.

PMID- 17179635
TI  - Carcinogenicity and chronic toxicity in rats and mice exposed by inhalation to
      1,2-dichloroethane for two years.
AB  - Carcinogenicity and chronic toxicity of 1,2-dichloroethane (DCE) were examined by
      inhalation exposure of groups of 50 F344 rats and 50 BDF1 mice of both sexes to
      DCE vapor or clean air as control for 6 h/d, 5 d/wk and 104 wk. The rats were
      exposed to 10, 40 or 160 ppm (v/v) DCE, while the mice were exposed to 10, 30 or
      90 ppm. The 2-yr exposure to DCE produced a dose-dependent increase in incidences
      of benign and malignant tumors, including subcutaneous fibroma, mammary gland
      fibroadenoma and peritoneal mesothelioma in male rats; subcutaneous fibroma and
      mammary gland adenoma, fibroadenoma and adenocarcinoma in female rats; and
      bronchiolo-alveolar adenoma and carcinoma, endometrial stromal polyp, mammary
      gland adenocarcinoma and hepatocellular adenoma in female mice. No exposure
      related change in the incidence of non-neoplastic lesions or in any
      hematological, blood biochemical or urinary parameter occurred in any DCE-exposed
      rat or mouse group. The types of tumors and their target organs found in this
      study were consistent with those observed in rats and mice administered DCE by
      gavage in a NCI study. Selection of the exposure concentrations was considered
      appropriate with reference to the maximum tolerated dose for the highest doses
      and an occupational exposure limit of DCE for the lowest dose. The present
      findings suggest that those carcinogenic responses be primarily considered for
      standard setting of occupational and environmental exposure to DCE.

PMID- 17179637
TI  - Subjective fatigue and stress hormone levels in urine according to duration of
      shiftwork.
AB  - To determine the associations between urinary catecholamines and cortisol and
      subjective complaints of fatigue in shiftworkers, we conducted a field survey of
      113 male shiftworkers at a manufacturing company in South Korea from late October
      to late November in 1999. The shiftwork system in the company was the backward
      rapidly rotating 4-crew 3-shift, with the morning shift starting at 7:30 AM.
      Using a self-report questionnaire, we assayed demographic characteristics, past
      medical history and working hours, as well as subjective complaints of fatigue in
      3 categories of questionnaire. We found that, among workers with less than 5 yr
      of shiftwork experience, the concentrations of norepinephrine, epinephrine (Epi),
      and dopamine during the afternoon shift were positively correlated with Set II
      (difficulties in concentration) and Set III (projection of disintegration) of
      subjective fatigue symptoms. In addition, Epi concentrations were positively
      correlated with Set I (drowsiness and dullness), II, and III of subjective
      fatigue symptoms during the night shift. However, among workers with 5 or more
      years of shiftwork experience, there was no significant positive correlation
      between urinary catecholamine and subjective fatigue symptoms. In the long term
      shiftwork experience group, only the complaints scores of Set II fatigue symptoms
      (difficulties in concentration) during the morning shift were significantly
      higher than those of the short-term shiftwork experience group within the same
      shift.

PMID- 17179636
TI  - Behavior of rock wool in rat lungs after exposure by nasal inhalation.
AB  - To evaluate the safety of rock wool (RW) fibers, we examined the biopersistence
      of RW fibers in the lungs of rats, based on the changes of fiber number and fiber
      size in the length and width, in a nose-only inhalation exposure study. Twenty
      male Fischer 344 rats (6 to 10 wk old) were exposed to RW fibers at a fiber
      concentration of 70.6 (20.4) fiber/m(3) and a dispersion density of 30.4 (6.6)
      mg/m(3) [arithmetic mean (SD)] continuously for 3 h daily for 5 consecutive days.
      Five rats each were sacrificed shortly after exposure ended (baseline group) and
      at 1, 2, and 4 wk after exposure, and their lung tissues were ashed by a low
      temperature plasma-asher. The numbers and sizes of fibers in the ash samples were
      determined using a phase contrast microscope and a computed image analyzer. The
      fiber numbers in the lungs at 4 wk after exposure had significantly decreased
      from the baseline value, i. e. shortly after exposure (p<0.05). The half-lives of
      RW fibers calculated using the one-compartment model were 32 d for total fibers
      and 10 d for fibers longer than 20 microm in length. Fiber number was 53.6% of
      the baseline at 4 wk after exposure (baseline group=100%). Likewise, fiber sizes
      had significantly decreased at 4 wk after exposure (p<0.05), probably because
      fibers had been dissolved in body fluid, phagocytosed by alveolar macrophages or
      discharged from the body by mucociliary movement. In future studies, it will be
      necessary to examine the carcinogenicity of RW fibers through long-term
      inhalation studies.

PMID- 17179638
TI  - The effects of pre-entry career maturity and support networks in workplace on
      newcomers' mental health.
AB  - The present study examined the effects of pre-entry experiences (i.e. career
      maturity), as well as support networks (i.e. informational and friendship), on
      newcomers' mental health (i.e. depression, self-esteem, psychosomatic symptoms,
      and work motivation). We performed a longitudinal study of 890 men and women who
      first entered the workplace in 2003. Surveys were distributed at two time points:
      just prior to entering the workplace, and two months after entering. Results
      indicated that career maturity related positively to newcomers' mental health,
      and newcomers with high career maturity were more successful in establishing
      positive relationships with superiors and co-workers. Although, informational
      support networks positively related to work motivation, friendship networks did
      not show any direct effects on mental health. These results underscore the
      crucial roles of career maturity and informational networks in facilitating the
      transition to the workplace. The results also provide empirical support for an
      expanded view of the importance of pre-entry experiences to workplace newcomers'
      mental health.

PMID- 17179639
TI  - Effects of inhalation exposure to propylene oxide on respiratory tract,
      reproduction and development in rats.
AB  - Nasal, respiratory, reproductive and developmental toxicities of propylene oxide
      (PO) were examined by exposing male and female Sprague-Dawley rats to PO vapor by
      inhalation at a concentration of 0 (control), 125, 250, 500 or 1,000 ppm for 6
      h/d, 7 d/wk, during a 5- to 6-wk period, including premating, mating and
      postmating or gestation. The inhalation exposure to 1,000 ppm PO seriously
      affected parental survival, the upper and lower respiratory tract, male and
      female reproductive systems, motor function, and fetal survival and development,
      whereas the exposure to 500 ppm or less primarily caused nasal lesions without
      any sign of reproductive or developmental toxicity. Because atrophy of the
      olfactory epithelium in the male rats exposed to 250 ppm was the most sensitive
      endpoint for PO toxicity, the NOAEL was determined to be 125 ppm for the nasal
      endpoint. An additional inhalation experiment was carried out to further examine
      developmental toxicity by exposing pregnant rats to 0, 125, 250, 500, 750 or
      1,000 ppm PO during a 2-wk period of gestation, Day 6 through Day 19. The 2-wk
      inhalation experiment revealed that reduced fetal body weights and delayed
      ossification occurred in association with significantly reduced body weights of
      the dams exposed to 750 and 1,000 ppm, whereas neither fetal death nor
      teratogenicity occurred at those two exposure levels. It was concluded that the
      developmental toxicity of fetal death was manifested at parentally toxic exposure
      levels above 500 ppm, a level which seriously affected parental survival, the
      upper and lower respiratory tracts and reproductive system.

PMID- 17179640
TI  - Mental health of healthcare workers who experience needlestick and sharps
      injuries.
AB  - Healthcare workers (HCWs) are exposed daily to the risk of injury by needlesticks
      and other medical instruments. However, the psychiatric impacts of such injuries
      have not been evaluated. The aim of this study was to evaluate the mental health
      status of HCWs with experiences of needlestick and sharps injuries. A cross
      sectional written survey was performed. The psychological symptoms before injury
      and current status were measured using the Beck Depression Inventory (BDI),
      Hamilton Anxiety Scale (HAM-A) and Perceived Stress Scale (PSS). The proportions
      of HCWs with and without needlestick and sharps injuries were 71.1% (n=263) and
      28.9% (n=107), respectively. HAM-A and BDI scores were significantly higher among
      HCWs with injury experiences (p<0.01). HCWs with injury experiences exhibited
      higher PSS and BDI scores after the injury and higher levels of anxiety and
      depression. Particular attention should be directed towards the psychological
      consequences of needlestick and sharps injuries in HCWs.

PMID- 17179641
TI  - Toxicity study of the volatile constituents of Myoga utilizing acute dermal
      irritation assays and the Guinea-pig Maximization test.
AB  - Myoga is a fragrant plant which is the special product of Japan and is cultivated
      throughout Japan. According to our earlier investigation (unpublished data) of
      myoga cultivators in Japan, 8 of 35 cultivators experienced contact dermatitis in
      the harvest season. The purpose of this study was to assess the allergenicity of
      myoga and its major volatile components. The volatile components of myoga were
      analyzed by gas chromatograph (GC). They included a-pinene, beta-pinene and R-(+)
      limonene. We performed a toxicity study of each of the major fragrant components
      of myoga using acute dermal irritation assays and the Guinea-Pig Maximization
      test (GPMT) in order to probe the mechanism of allergic contact dermatitis. In
      acute dermal irritation assays, alpha-pinene, beta-pinene and limonene showed
      positive responses at concentrations of 4%; limonene oxide at 20% and myoga
      showed a positive response at concentrations of 100%. From the results of the
      GPMT, according to Kligman scores, limonene oxide was identified as an extreme
      skin sensitizer and myoga as a mild skin sensitizer. The results of the present
      study show that R-(+)-limonene is the most important allergen amongst the
      chemical components of myoga, and we consider it to be the reason why myoga
      cultivators experience allergic contact dermatitis.

PMID- 17179642
TI  - Association of psychological well-being with oral conditions in Japanese workers.
AB  - Although the effect of disorders on psychological well-being is well-known, there
      are few studies focusing on oral conditions at the worksite. The present study
      examined the association between psychological well-being and oral conditions of
      Japanese workers. A cross-sectional study was performed using data from 1381
      Japanese civil service officers aged 20-59 yr old. Psychological well-being was
      measured with the 12-item version of the General Health Questionnaire (GHQ-12) in
      a comprehensive health questionnaire, while measures for oral condition included
      self-rated oral health, oral symptoms and clinical indicators: dental caries,
      periodontal status and number of missing teeth. The mean GHQ scores according to
      the levels of each oral condition were estimated by analysis of variance,
      separately for males and females. Higher scores corresponded to poorer
      psychological well-being. Age, gender, smoking and type of occupation were
      adjusted in a multivariate analysis. Psychological well-being was not associated
      significantly with dental caries, periodontal status or number of missing teeth.
      The adjusted means of the GHQ scores for ;conscious of appearance of mouth' were
      significantly different among the categories for both genders (male: p<0.001,
      female: p=0.018). For five of six oral symptoms, the adjusted means of GHQ scores
      were lowest for those respondents who rated their oral symptoms as ;never or
      hardly ever.' Our results did not show that psychological well-being was
      associated with oral conditions measured by clinical indicators. However, an
      association was found between some oral symptoms and psychological well-being.
      Absence of oral symptoms seems to be related to better psychological well-being.

PMID- 17179643
TI  - Effects of the job stress education for supervisors on psychological distress and
      job performance among their immediate subordinates: a supervisor-based randomized
      controlled trial.
AB  - As job stress is now one of the biggest health-related problems in the workplace,
      several education programs for supervisors have been conducted to reduce job
      stress. We conducted a supervisor-based randomized controlled trial to evaluate
      the effects of an education program on their subordinates' psychological distress
      and job performance. The subjects were 301 employees (46 supervisors and 255
      subordinates) in a Japanese sake brewery. First, we randomly allocated
      supervisors to the education group (24 supervisors) and the waiting-list group
      (22 supervisors). Then, for the allocated supervisors we introduced a single
      session, 60-min education program according to the guidelines for employee mental
      health promotion along with training that provided consulting skills combined
      with role-playing exercises. We conducted pre- and post-intervention (after 3
      months) surveys for all subordinates to examine psychological distress and job
      performance. We defined the intervention group as those subordinates whose
      immediate supervisors received the education, and the control group was defined
      as those subordinates whose supervisors did not. To evaluate the effects, we
      employed a repeated measures analysis of variance (ANOVA). Overall, the
      intervention effects (time x group) were not significant for psychological
      distress or job performance among both male (p=0.456 and 0.252) and female
      (p=0.714 and 0.106) subordinates. However, young male subordinates engaged in
      white-collar occupations showed significant intervention effects for
      psychological distress (p=0.012) and job performance (p=0.029). In conclusion,
      our study indicated a possible beneficial effect of supervisor education on the
      psychological distress and job performance of subordinates. This effect may vary
      according to specific groups.

PMID- 17179644
TI  - Association between intention to stay on the job and job satisfaction among
      Japanese nurses in small and medium-sized private hospitals.
AB  - In order to examine the relationship between the intention to stay on the job and
      job satisfaction among Japanese nurses, and to obtain clues for preventing
      turnover, we conducted a questionnaire survey. The subjects involved in the
      survey included 625 female nurses (registered nurses, licensed practical nurses
      and assistant nurses) working in 4 small and medium-sized private hospitals,
      excluding directors of nursing. Of the 625 questionnaires distributed, 556
      (89.0%) were returned. After excluding the questionnaires with missing values,
      480 questionnaires were analyzed (effective response rate, 76.8%). The average
      age of the respondents was 32.8 yr (range: 20-65). The content of the
      questionnaire was nurse attributes, job satisfaction (30 items) and intention to
      stay on the job. For job satisfaction, factor analysis (principal factor method
      and promax rotation) was performed, and factors with an eigenvalue of > or =1
      were extracted. Six factors were extracted by factor analysis. These factors were
      interpreted as "Work as specialists" (1st factor), "Relationship with superiors"
      (2nd factor), "Comfortable life" (3rd factor), "Relationship among nurses" (4th
      factor), "Communication with physicians" (5th factor) and "Working conditions"
      (6th factor). The factor scores were calculated and used as a scale for the
      evaluation of job satisfaction. To investigate the factors associated with
      intention to stay on the job among nurses, the standard partial regression
      coefficient was computed by multiple linear regression analysis, with intention
      to stay on the job as the dependent variable, and nurse attributes and job
      satisfaction (factor scores) as independent variables. Various factors including
      the organizational culture of each hospital may affect the relationship between
      job satisfaction and the intention to stay on the job. In order to adjust for
      these factors, differences among hospitals were included in the statistical model
      as independent variables. The result of the multiple regression analysis suggests
      that the intention to stay on the job was higher among nurses who were older and
      more satisfied with work as specialists (1st factor) and working conditions (6th
      factor).

PMID- 17179645
TI  - Study of a mortality surge among transport workers in Japan.

PMID- 17179646
TI  - Genotoxic risks to nurses from contamination of the work environment with
      antineoplastic drugs in Japan.
AB  - The aims of the present study were to clarify the work environment contamination
      by antineoplastic drugs in a hospital ward and to assess the genotoxic risks to
      nurses who routinely handle antineoplastic drugs in Japan. The exposed group
      consisted of 19 female nurses who routinely handled antineoplastic drugs. The
      control group consisted of 18 female nurses who did not handle antineoplastic
      drugs in the same hospital as the exposed group. The genotoxicity of the 19
      antineoplastic drugs used in the hospital ward and 8 wipe samples of the
      workbench after handling of antineoplastic drugs were measured using the umu
      assay. Lymphocyte DNA damage (tail length) was measured with alkaline methods of
      the single cell gel electrophoresis assay (comet assay). Of the 19 antineoplastic
      drugs, dacarbazine, bleomycin, daunorubicin, doxorubicin, pirarubicin,
      carboplatin, cisplatin and etoposide induced genotoxicity. Of the 8 sampling d,
      the umu activity of the wipe sample was positive on 3 d. Contamination of the
      workbench was found when the nurses handled more drugs than on other days. The
      medians of the tail length in the comet assay were 8.5 and 5.1 microm,
      respectively, for the exposed and control groups, with a significant difference
      (p=0.004 by Mann-Whitney's U-test). In the present study, the nurses of the
      exposed group were considered to have been exposed to antineoplastic drugs and
      lymphocyte DNA damage of the exposed group was suggested to be induced by
      antineoplastic drugs.

PMID- 17179647
TI  - Effects of 2.45 GHz electromagnetic fields with a wide range of SARs on bacterial
      and HPRT gene mutations.
AB  - Present day use of mobile phones is ubiquitous. This causes some concern for
      human health due to exposure to high-frequency electromagnetic fields (HFEMF)
      from mobile phones. Consequently, we have examined the effects of 2.45 GHz
      electromagnetic fields on bacterial mutations and the hypoxanthine-guanine
      phosphoribosyl transferase (HPRT) gene mutations. Using the Ames test, bacteria
      were exposed to HFEMF for 30 min at specific absorption rates (SARs) from 5 to
      200 W/kg. In all strains, there was no significant difference in the frequency of
      revertant colonies between sham exposure and HFEMF-exposed groups. In examination
      of mutations of the HPRT gene, Chinese hamster ovary (CHO)-K1 cells were exposed
      to HFEMF for 2 h at SARs from 5 to 200 W/kg. We detected a combination effect of
      simultaneous exposure to HFEMF and bleomycin at the respective SARs. A
      statistically significant difference was observed between the cells exposed to
      HFEMF at the SAR of 200 W/kg. Cells treated with the combination of HFEMF at SARs
      from 50 to 200 W/kg and bleomycin exhibited increased HPRT mutations. As the
      exposure to HFEMF induced an increase in temperature, these increases of mutation
      frequency may be a result of activation of bleomycin by heat. We consider that
      the increase of mutation frequency may be due to a thermal effect.

PMID- 17179648
TI  - Protective effects of inosine on mice subjected to lethal total-body ionizing
      irradiation.
AB  - Mammals can barely survive total-body ionizing irradiation greater than 10 Gy. To
      date, there are few drugs available for radioprotective therapy under such
      circumstances. Inosine, a natural derivative of adenosine, has been known to
      provide powerful protection for many kinds of cells and tissues against various
      insults both in vitro and in vivo. In the present study, we examined whether
      inosine was also beneficial for mammals subjected to an absolutely lethal total
      body ionizing irradiation. Immediately after adult Balb/c mice were exposed to
      (60)Co gamma-rays at a single dose of 12 Gy, a moiety of them were administered
      daily with inosine or adenosine, either at doses of 375 or 750 micromol/kg up to
      death, and their body weight and survival time were recorded. Some irradiated
      mice were administered inosine or adenosine daily at doses of 750 micromol/kg and
      assessed for spatial memory abilities using the Morris water maze. The results
      demonstrated that, although inosine could not prevent body weight loss in
      irradiated mice, it was able to significantly prolong their survival time at
      doses of 750 micromol/kg. Moreover, inosine but not adenosine could suppress
      spatial memory deficit in irradiated mice. The data suggested that inosine had
      protective effects on mammals suffering from total-body ionizing irradiation at a
      single lethal dose.

PMID- 17179649
TI  - Molecular characteristics of porcine Fas-associated death domain (FADD) and
      procaspase-8.
AB  - To reveal the intracellular signal transduction molecules involved in granulosa
      cell apoptosis in porcine ovarian follicles, we cloned the porcine Fas-associated
      death domain (FADD), an adaptor protein for the cell death receptor, and
      procaspase-8, an initiator caspase. Porcine FADD (pFADD) was 636 bp (211 amino
      acids: aa) long and showed 74.0 and 65.4% homology with human and murine FADD,
      respectively. Porcine procaspase-8 (pprocaspase-8) was 1,431 bp (476 aa) long and
      70.6 and 63.4% homologous with human and murine procaspase-8, respectively. To
      confirm the apoptosis-inducing abilities, we constructed pFADD and pprocaspase-8
      cDNA expression vectors with enhanced green fluorescence protein (EGFP) and then
      transfected them into human uterine cervix tumor (HeLa-K), human granulosa cell
      derived (KGN), murine granulosa-derived tumor (KK1), and porcine granulosa cell
      derived (JC410) cells. When pFADD and pprocaspase-8 were overexpressed, cell
      death was induced in these transfected cells. However when caspase-inhibitor p35
      was cotransfected, cell death was inhibited. The pFADD and pprocaspase-8 genes
      are well conserved, as are the physiological functions of their products.

PMID- 17179650
TI  - Growing porcine oocyte-granulosa cell complexes acquired meiotic competence
      during in vitro culture.
AB  - The aim of this study was to establish a culture system to improve the meiotic
      competence of porcine oocyte-granulosa cell complexes (OGCs) obtained from
      preantral or early antral follicles. Porcine OGCs were recovered from follicles
      with diameters of 230-300 (preantral follicles), 300-500, and 500-700 mum (early
      antral follicles) using scalpels. The OGCs were cultured for 2 weeks in culture
      medium. We examined the effects of the sizes of the follicles from which OGCs
      were recovered, the concentrations of polyvinylpyrrolidone (PVP, 0-8%) in the
      culture medium, and 2 types of culture dish (Falcon 3002 vs 1007) on formation of
      the antrum of OGCs. After culture, the oocytes were matured for 44 h to assess
      their meiotic competence. OGCs recovered from small follicles (230-500 microm)
      required longer (P<0.05) than larger follicles to form the antrum structure. The
      percentage of OGCs forming the antrum structure that were cultured in 2% PVP
      (31%) was higher (P<0.05) than for those cultured in other PVP concentrations (0
      11%). The percentages of antrum-structure formation for OGCs cultured on Falcon
      3002 (83% for 2% PVP and 60% for 4% PVP) were higher (P<0.05) than those cultured
      on Falcon 1007 (47% for 2% PVP and 9% for 4% PVP). Furthermore, all of the intact
      oocytes that were obtained from culture of OGCs and that formed an antrum were in
      the GV stage (n=28). When these immature oocytes were cultured for 44 h, the
      percentage of oocytes that reached the metaphase II stage (25%, n=68) was higher
      (P<0.0001) than that of oocytes matured without culture (0.7%, n=137). The
      results of the present study show that porcine OGCs obtained from preantral or
      early antral follicles acquire meiotic competence in vitro.

PMID- 17179651
TI  - Cytogenetic analysis and developmental assessment of mouse embryos derived from
      in vitro fertilization of oocytes reconstructed by meiosis-II chromosome
      transplantation.
AB  - An electrofusion methodology for transferring meiosis-II chromosomes (M-II-t) has
      not been completely established. The present study compared the use of two
      temperatures (fusion at 37 C for Group A and 25 C for Group B) during an
      electrofusion procedure for mouse oocyte M-II-t and investigated the cytogenetic
      normality and developmental competence of embryos derived from in vitro
      fertilization using oocytes reconstructed by M-II-t. The M-II-t oocytes were
      fertilized in vitro and cultured to the blastocyst stage; the resultant embryos
      were analyzed cytogenetically. Subsequently, chromosomal normality of the
      resultant embryos at the prometaphase stage of first cleavage division and the
      integrity of the meiosis-II spindles of the reconstructed oocytes were analyzed.
      The success rate of electrofusion in Group B was 92.1%, which was significantly
      different from that in Group A (49.2%) (P<0.05). The fertilization rates (A,
      80.7%; B, 77.2%) and development rates (A, 70.9%; B, 65.5%) in the M-II-t groups
      were significantly lower than those in the control group (95.0 and 92.2%,
      respectively) (P<0.05). The incidence of chromosomal abnormalities in the Group A
      embryos (20.5%) at the blastocyst stage was significantly higher than that in the
      control group embryos (8.5%) (P<0.05), but the incidence of chromosomal
      abnormalities in Group B (12.5%) was not significantly different compared with
      the other groups. A temperature of 25 C during the electrofusion procedure for M
      II-t resulted in a good fusion rate, good development rate, and efficient
      production of chromosomally normal blastocysts. Furthermore, the incidence of
      chromosomal abnormalities in the first cleavage embryos at the prometaphase stage
      in Group B (9.6%) did not differ significantly from that in the control group
      (6.6%). The spindle morphology of the M-II-t oocytes in Group B was normal.

PMID- 17179652
TI  - The Effects of GABA on embryonic gonadotropin-releasing hormone neurons in rat
      hypothalamic primary culture.
AB  - Gonadotropin-releasing hormone (GnRH) neurons arise in the olfactory placode,
      migrate into the preoptic area (POA), and then extend axons to the median
      eminence during embryogenesis. Little information is available concerning the
      properties of GnRH neurons during the late gestational period when GnRH neurons
      reach the POA and form neuronal networks, although many studies have examined
      such properties during earlier developmental stages or the postnatal period. The
      present study was performed to elucidate the involvement of gamma-aminobutyric
      acid (GABA), one of the major neurotransmitters modifying GnRH neural activity,
      in regulation of GnRH gene expression on embryonic day 18.5 (E18.5) using
      transgenic rats expressing enhanced green fluorescence protein (EGFP) under the
      control of GnRH promoter. First, using RT-PCR, the mRNA of two isoforms of the
      GABA-synthesizing enzyme glutamic acid decarboxylase (GAD), GAD65 and GAD67 was
      detected in E18.5 embryonic POA-containing tissues. GAD67-positive cells were
      also demonstrated in close vicinity to GnRH-positive cells by
      immunohistochemistry, and immunoreactivity for both the GABA-A and GABA-B
      receptor subunits was detected in GnRH neurons. Next, primary cultures derived
      from anterior hypothalamic tissue of E18.5 embryos were prepared, and the effects
      of GABA and its agonists on GnRH promoter activity were evaluated using EGFP
      expression as a marker. GABA and the GABA-A receptor agonist muscimol, but not
      the GABA-B receptor agonist baclofen, significantly increased the EGFP
      positive/GnRH-positive cell ratio. These results suggest that GABA plays a role
      in stimulating GnRH gene expression through GABA-A receptors in embryonic GnRH
      neurons in late gestational stages.

PMID- 17179653
TI  - Involvement of granulin in estrogen-induced neurogenesis in the adult rat
      hippocampus.
AB  - Recent studies have demonstrated the presence of neurogenesis in the adult
      mammalian hippocampus, and it has been suggested that estrogen and various growth
      factors influence the processes of adult neurogenesis. The present study assessed
      cell proliferation in the dentate gyrus and the mRNA expression levels of
      granulin, insulin-like growth factor-I (IGF-I), and brain-derived neurotrophic
      factor (BDNF) in the hippocampus 4 h after treatment with estradiol benzoate (EB)
      in 3- and 12-month old ovariectomized rats. At 3 months of age, mRNA expression
      of granulin precursor and cell proliferation were increased by EB treatment,
      although the mRNA expressions of IGF-I and BDNF remained unchanged. At 12 months
      of age, however, neither mRNA expression of the three genes nor cell
      proliferation in the dentate gyrus were affected by EB treatment. In addition,
      17beta-estradiol enhanced the proliferation of neural progenitor cells derived
      from hippocampal tissue of 3-month-old female rats in vitro; this was inhibited
      by neutralization of granulin with specific antibody. These results suggest that
      estrogen induces granulin gene expression in the hippocampus and that the product
      of this gene is involved in the mitogenic effects of estrogen in the dentate
      gyrus, although the responses to estrogen decline with age.

PMID- 17179654
TI  - Arginase alteration in the reproductive system of alloxan-diabetic dogs.
AB  - This study was conducted to evaluate possible alteration in the activity of
      arginase, an important enzyme of cell proliferation and vascular smooth muscle
      contraction regulator in diabetics, that may be correlated with low fertility in
      diabetic patients. In this investigation, 6 apparently healthy adult male dogs
      were selected and divided in two groups, diabetics and non-diabetics. Diabetes
      mellitus was induced in one group by intravenous (IV) injection of alloxan (100
      mg/kg). Dogs with a fasting blood glucose (FBS) of more than 200 mg/dl were
      considered to be diabetic. Four weeks following induction of diabetes mellitus,
      the animals in both groups were anesthetized by an IV injection of sodium
      thiopental. Livers and whole reproductive systems, including the testes, penis,
      urethra, and prostate, were dissected. The epididymides, corpus cavernosum,
      corpus spongiosum, penile urethra, and vas deferens were also dissected and
      removed from the reproductive system. Arginase activity and total protein were
      measured by the urea and Lowry's methods respectively in above mentioned
      sections. Plasma testosterone was determined by the radioimmunoassay method. The
      results showed significantly (P<0.05) increased arginase specific activity (ASA)
      in the liver, epididymis, prostate, corpus cavernosum and corpus spongiosum of
      the diabetic dogs. In the reproductive system of the diabetic dog, the maximum
      and minimum ASA was seen in the corpus cavernosum and testes, respectively
      (105.12 +/- 8.76 vs. 25.0 +/- 0.55). No such variation was observed in the ASA of
      normal dogs (39.0 +/- 5.47 vs. 25.0 +/- 5.47). There was no significant
      difference in plasma testosterone level between the groups. In conclusion,
      diabetes increased the ASA in liver, prostate, epididymis, corpora cavernosa, and
      corpora spongiosum of the male dogs and may contribute to erectile dysfunction or
      low fertility in diabetics.

PMID- 17179655
TI  - Maternal gene transcription in mouse oocytes: genes implicated in oocyte
      maturation and fertilization.
AB  - Maternal gene expression is an important biological process in oocyte maturation
      and early cleavage. To gain insights into oocyte maturation and early embryo
      development, we used microarray analysis to compare the gene expression profiles
      of germinal vesicle (GV)- and metaphase II (MII)-stage oocytes. The differences
      in spot intensities were normalized and grouped using the Avadis Prophetic
      software platform. Of the 12164 genes examined, we found 1682 genes with more
      highly expression in GV-stage oocytes than in MII-stage oocytes, while 1936 genes
      were more highly expressed in MII-stage oocytes (P<0.05). The genes were grouped
      on the basis of the Panther classification system according to their involvement
      in particular biological processes. The genes that were up-regulated in GV
      oocytes were more likely to be involved in protein metabolism and modification,
      the mitotic cell cycle, electron transport, or fertilization or belong to the
      microtubule/cytoskeletal protein family. The genes specifically upregulated in
      the MII oocytes were more likely to be involved in DNA replication, amino acid
      metabolism, or expression of G protein-coupled receptors and signaling molecules.
      Identification of genes that are preferentially expressed at particular oocyte
      maturation stages provides insights into the complex gene regulatory networks
      that drive oocyte maturation and fertilization.

PMID- 17179656
TI  - Effect of daily treatment with Thai herb, Kaempferia parviflora, in Hershberger
      assay using castrated immature rats.
AB  - The aim of the present study was to investigate the testosterone-like effect of
      Kaempferia parviflora (KP). Castrated immature rats were randomized and divided
      into two groups (control and KP-treatment groups). The rats (n=7-8) were treated
      daily for 5 days by oral route with water in the control group and 1,000 mg/kg of
      KP in the treatment group. All rats were decapitated 24 h after their last dose
      and then blood samples were collected for assay of serum FSH, LH, testosterone,
      progesterone and corticosterone levels. The seminal vesicles plus coagulating
      glands, ventral prostate, levator ani muscle plus bulbocavernosus muscle, glans
      penis, kidneys and the adrenal glands were collected and weighed for organ wet
      weight. Body weight and weight of food intake were recorded throughout the study
      period. The results show that relative body weight gain in the KP-treatment group
      was significantly increased 24 and 48 h after the first dose (P<0.05) and then
      was indistinguishable from the control group. There were no significant
      differences in the relative reproductive and non-reproductive organ weights
      between the groups, although all organ weights, except for the glans penis,
      tended to increase in the KP-treatment group. The serum testosterone levels were
      significantly increased in the KP-treatment group. There were no significant
      differences in the serum FSH, LH, progesterone, or corticosterone levels between
      the groups, even though the serum progesterone level tended to increase and serum
      LH level tended to decrease in the KP-treatment group. The present study
      indicates that KP has no testosterone-like effect on reproduction in male rats.

PMID- 17179657
TI  - Apoptosis inhibition by insulin-like growth factor (IGF)-I during in vitro
      maturation of bovine oocytes.
AB  - Recently, significant progress has been achieved in improving the yield of good
      quality embryos in vitro. However, efforts are still required to recognize the
      factors and understand the mechanisms of oocyte maturation, which are essential
      for subsequent embryo development. The aims of the present study were to
      determine the frequency of apoptosis in oocytes recovered from slaughterhouse
      ovaries and to investigate whether insulin-like growth factor (IGF)-I action
      during oocyte maturation in vitro may withhold apoptosis and improve oocyte
      quality. Only oocytes of proper morphology with homogenous ooplasm and compact
      cumulus cells were selected for this study. All oocytes recovered from the
      slaughterhouse ovaries were divided into two groups. One group of oocytes, chosen
      for apoptosis detection, was examined immediately after recovery. The other group
      of oocytes was maturated in vitro. Oocytes were maturated with IGF-I
      supplementation (100 ng/ml). Oocytes without supplementation were used as a
      control. Apoptosis in oocytes was determined by positive results of TUNEL assay
      and active caspase labeling. The percentage of apoptotic oocytes detected by
      TUNEL fell to zero when the maturation medium was supplemented with IGF-I in
      comparison to the control matured oocytes (0 vs. 9.87%; P<0.05). However, active
      caspase labeling was only slightly decreased in the IGF-I matured oocytes
      compared with the control matured oocytes (1.13 vs. 2.08%; P<0.05). The results
      indicate that IGF-I may serve as an anti-apoptotic factor during oocyte
      maturation. We suggest that IGF-I may inhibit apoptosis in oocytes at the stage
      of caspase activation and may prevent further advancement of oocyte apoptosis.

PMID- 17179658
TI  - Changes in rat uterine and cervical phospholipase A2 activity following
      progesterone agonist or antagonist administration at term.
AB  - Our previous study revealed that a fall in plasma progesterone (P(4)) level was
      associated with a transient increase in cytosolic phospholipase A(2) (PLA(2))
      activity and prostaglandin F(2)alpha level in the rat uterus and cervix during
      natural parturition. This study determined the changes in the PLA(2) activities
      during modulated occurrence of delivery by P(4) antagonist or agonist late in
      pregnancy. In rats undergoing P(4) antagonist-induced preterm delivery, the
      PLA(2) activities of both uterine and cervical cytosol significantly decreased 12
      h after the challenge and tended to be attenuated within 72 h. The plasma P(4)
      level altered in a similar pattern. Blockade of delivery by chronic treatment
      with P(4) agonist was not associated with changes in uterine PLA(2) activity
      compared with that in normally delivering rats, although there was a persistent
      rise in cervical PLA(2) activity. The obtained data indicates that the PLA(2)
      activities in rat uterine and cervical cytosol are not regulated solely by P(4)
      and that delivery can occur without activation of this enzyme.

PMID- 17179659
TI  - The ABCs (Antibody, B cells, and Carbohydrate epitopes) of cholera immunity:
      considerations for an improved vaccine.
AB  - Cholera, a diarrheal disease, is known for explosive epidemics that can quickly
      kill thousands. Endemic cholera is a seasonal torment that also has a significant
      mortality. Not all nations with extensive rural communities can achieve the
      required infrastructure or behavioral changes to prevent epidemic or endemic
      cholera. For some communities, a single-dose cholera vaccine that protects those
      at risk is the most efficacious means to reduce morbidity and mortality. It is
      clear that our understanding of what a protective cholera immune response is has
      not progressed at the rate our understanding of the pathogenesis and molecular
      biology of cholera infection has. This review addresses V. cholerae
      lipopolysaccharide (LPS)-based immunogens because LPS is the only immunogen
      proven to induce protective antibody in humans. We discuss the role of anti-LPS
      antibodies in protection from cholera, the importance and the potential role of B
      cell subsets in protection that is based on their anatomical location and the
      intrinsic antigen-receptor specificity of various subsets is introduced.

PMID- 17179660
TI  - Protective immunity against Bordetella pertussis by a recombinant DNA vaccine and
      the effect of coinjection with a granulocyte-macrophage colony stimulating factor
      gene.
AB  - A recombinant pertussis DNA vaccine was described here with its immunogenicity
      and the ability to induce protection against B. pertussis infection in mice.
      Three immunodominant antigen gene fragments of pertussis, pertussis toxin subunit
      1 (pts1), fragments of pertactin (prn) and filamentous hemagglutinin (fha), were
      recombined as fragment pts1-prn-fha named ppf, and it was cloned to plasmid pVAX1
      as pVAX1/ppf. Compared to those injected with pVAX1, the mice injected with
      pVAX1/ppf significantly elicited more antigen specific antibody anti-PTS1, anti
      PRN, anti-FHA and cytokine IL-10, IFN-gamma. When pGM-CSF was coinjected with
      pVAX1/ppf, the mice showed significantly increases of the three antibodies and
      cytokine IL-10, IL-4, IFN-gamma and TNF-alpha compared to those injected with
      pVAX1 only. The mice in group pVAX1/ppf & pGM-CSF, in particular; induced much
      more anti-PTS1, IL-4 and TNF-alpha than those in group pVAX1/ppf. In the
      intracerebral mouse protection test, the mice immunized with pVAX1/ppf or
      pVAX1/ppf & pGM-CSF induced protection to a lethal dose of B. pertussis. The
      results indicate that recombinant DNA vaccine and pGM-CSF coinjection can induce
      protective immunity against B. pertussis, demonstrating a valuable method to
      prevent pertussis.

PMID- 17179661
TI  - Analysis of bacterial community structure in the natural circulation system
      wastewater bioreactor by using a 16S rRNA gene clone library.
AB  - A variety of physical and chemical parameters are routinely monitored during
      operation of the Natural Circulation System, a wastewater purification bioreactor
      in which only natural materials and no synthetic chemicals are used. However, the
      microbial community structures existing in the Natural Circulation System have
      not been well characterized. Thus, bacterial community structure and composition
      in this system were studied using clone library analysis of 16S ribosomal RNA
      genes amplified using PCR with universal bacterial primer sets. The PCR products
      were then subcloned into the pGEM-T vector. Each unique restriction fragment
      length polymorphism pattern, created by using two pairs of restriction
      endonucleases, was designated as an operational taxonomic unit (OTU). The Natural
      Circulation System comprises five tanks, the second and third of which play a
      major role in the bioreactor. Clone library pro-files and principal component
      analysis revealed differences in the bacterial community structures of the second
      (anaerobic chamber) and the third (aerobic chamber) tanks. However, the beta
      proteobacteria, Bacteroidetes/ Chlorobi and gamma-proteobacteria groups were
      dominant in both tanks. Bacterial composition was more complex in the second tank
      (107 OTUs) than in the third tank (68 OTUs). Of a total of 154 OTUs in the clone
      libraries, only 21 were common to the two tanks. The results obtained in this
      study should provide important information for future research into and
      management of the Natural Circulation System wastewater bioreactor.

PMID- 17179662
TI  - Screening of upregulated genes in suckling mouse central nervous system during
      the disease stage of rabies virus infection.
AB  - The pathogenesis of hydrophobia remains unclear. The aim of this study was to
      identify the differentially upregulated genes that correlated with disease
      development in an experimental mouse model to provide better understanding of
      pathological mechanisms in rabies. The present work employed Clontech mouse array
      1.2 II containing 1,176 gene transcripts. Suckling mice were intracerebrally
      infected with canine rabies virus. The gene expression profiles on day 2, 4 and 6
      post inoculation were followed. The results show genes whose expression increased
      at least twofold above the control, mock-infected brain. The numbers of genes
      showing altered expression level were 29, 109 and 98 genes on day 2, 4 and 6,
      respectively. The genes with altered expression were classified into eight major
      groups, namely immune response, metabolism, receptor and transporter, growth
      factors, death mediated factors, transcription and translation factors,
      proteases, and kinases. The numbers of upregulated genes during the disease stage
      was much higher than during the asymptomatic stage. This suggested that direct
      interaction between RABV and target cells induced massive destruction of a
      cellular homeostasis which may lead to functional termination of the CNS.

PMID- 17179663
TI  - Genotypic analyses of Escherichia coli isolated from chickens with colibacillosis
      and apparently healthy chickens in Japan.
AB  - A genotypic comparison using pulsed-field gel electrophoresis (PFGE), amplified
      ribosomal restriction analysis (ARDRA) as well as PCRs targeting virulence
      associated genes reported elsewhere in avian pathogenic Escherichia coli(APEC)
      was made between E. coli strains isolated from chickens with colibacillosis and
      those from the feces of apparently healthy chickens in Japan. The majority (67%)
      of clinical isolates belonged to a certain phylogenetic ARDRA but not PFGE
      cluster, with virulence-related genes carried by ColV plasmid being markedly
      prevalent. The result suggests that APEC strains originated from the same
      "ancestor" in the course of E. coli evolution.

PMID- 17179664
TI  - Sulfatide and its synthetic analogues recognition by Moraxella catarrhalis.
AB  - Moraxella catarrhalis is one of the major pathogens of respiratory and middle ear
      infections. Attachment of this bacterium to the surface of human pharyngeal
      epithelial cells is the first step in the pathogenesis of infections. This study
      revealed that sulfatide might act as a binding molecule for the attachment of M.
      catarrhalis to human pharyngeal epithelial cells. Furthermore, six different
      synthetic sulfatides were found to inhibit the attachment of M. catarrhalis
      significantly at an optimum concentration of 10 microg/ml. Synthetic sulfatides
      may have the potential to be used as a therapy to prevent M. catarrhalis
      infections.

PMID- 17179665
TI  - Prolonged viral RNA detection in blood and lymphoid tissues from coxsackievirus
      B4 E2 orally-inoculated Swiss mice.
AB  - The spreading of viral RNA within Swiss Albino mice orally inoculated with
      coxsackievirus B4 E2 strain (CVB4 E2) was studied by using RT-PCR and semi-nested
      RT-PCR methods. Viral RNA was detected in various organs: pancreas, heart, small
      intestine, spleen, thymus, and blood at various postinfectious (p.i.) times
      ranging from 8 hr to 150 days. Our results show that (i) outbred mice can be
      infected with CVB4 E2 following an oral inoculation, which results in systemic
      spreading of viral RNA, (ii) CVB4 E2 infection can be associated with a prolonged
      detection of viral RNA in spleen, thymus and blood, up to 70 days p.i. and
      further in other organ tissues.

PMID- 17179666
TI  - Sensitivity of rabies virus to type I interferon is determined by the
      phosphoprotein gene.
AB  - The growth of a virulent strain of fixed rabies virus, Nishigahara, in mouse
      neuroblastoma NA cells treated with type I interferon (IFN) was compared with
      that of a derivative avirulent strain, Ni-CE. Nishigahara strain was slightly
      sensitive to IFN treatment but still grew more efficiently than did Ni-CE strain
      in IFN-treated NA cells. Furthermore, a virulent chimeric virus with the
      phosphoprotein gene from Nishigahara strain in the Ni-CE genome was less
      sensitive to IFN treatment than was Ni-CE strain, indicating that the IFN
      sensitivity is determined by the phosphoprotein gene of the virus.

PMID- 17179667
TI  - Autoimmune regulator (AIRE) gene is expressed in human activated CD4+ T-cells and
      regulated by mitogen-activated protein kinase pathway.
AB  - The autoimmune regulator (AIRE) gene is a gene responsible for autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy. Here we show that AIRE is
      expressed in human peripheral CD4-positive T-cells, and most highly in antigen
      and interleukin 2-stimulated T (IL-2T) cells. Mitogen-activated protein kinases
      (MAPKs), including MAPK kinase (MEK) 1/2 and p38 MAPK, were phosphorylated in IL
      2T cells and the expression of the AIRE gene was inhibited by a specific p38 MAPK
      inhibitor (SB203580), thereby indicating that AIRE gene expression is controlled
      by the MAPK pathway in IL-2T cells. These data suggested the possible
      significance of the AIRE gene in the peripheral immune system.

PMID- 17179668
TI  - Recombinant vaccinia DIs expressing simian immunodeficiency virus gag and pol in
      mammalian cells induces efficient cellular immunity as a safe immunodeficiency
      virus vaccine candidate.
AB  - A highly attenuated vaccinia virus substrain of Dairen-I (DIs) shows promise as a
      candidate vector for eliciting positive immunity against immune deficiency virus.
      DIs was randomly obtained by serial 1-day egg passages of a chorioarantoic
      membrane-adapted Dairen strain (DIE), resulting in substantial genomic deletion,
      including various genes regulating the virus-host-range. To investigate the
      impact of that deletion and of the subsequent insertion of a foreign gene into
      that region of DIs on the ability of the DIs recombinant to induce antigen
      specific immunity, we generated a recombinant vaccinia DIs expressing fulllength
      gag and pol genes of simian immunodeficiency virus (SIV) (rDIsSIV gag/pol) and
      studied the biological and immunological characteristics of the recombinant
      natural mutant. The rDIsSIV gag/pol developed a tiny plaque on the chick embryo
      fibroblast (CEF). Viral particles of rDIsSIV gag/pol as well as SIV Gag-like
      particles were electromicroscopically detected in the cytoplasm. Interestingly,
      the recombinant DIs strain grows well in CEF cells but not in mammalian cells.
      While rDIsSIV gag/pol produces SIV proteins in mammalian HeLa and CV-1 cells,
      recombinant modified vaccinia Ankara strain (MVA) expressing SIV gag and pol
      genes (MVA/SIV239 gag/pol) clearly replicates in HeLa and CV-1 cell lines under
      synchronized growth conditions and produces the SIV protein in all cell lines.
      Moreover, intradermal administration of rDIsSIV gag/pol or of MVA/SIV239 gag/pol
      elicited similar levels of IFN-gamma spot-forming cells specific for SIV Gag. If
      the non-productive infection characteristically induced by recombinant DIs is
      sufficient to trigger immune induction, as we believe it is, then a human
      immunodeficiency virus vaccine employing the DIs recombinant would have the twin
      advantages of being both effective and safe.

PMID- 17179669
TI  - Identification and characterization of a novel human collectin CL-K1.
AB  - Collectins are a family of C-type lectins with two characteristic structures,
      collagen like domains and carbohydrate recognition domains. They recognize
      carbohydrate antigens on microorganisms and act as host-defense. Here we report
      the cloning and characterization of a novel collectin CL-K1. RT-PCR analyses
      showed CL-K1 mRNA is present in all organs. The deduced amino acid sequence and
      the data from immunostaining of CL-K1 cDNA expressing CHO cells revealed that CL
      K1 is expressed as a secreted protein. CL-K1 is found in blood by immunoblotting
      and partial amino acid analyses. CL-K1 showed Ca(2+)-dependent sugar binding
      activity of fucose and weakly mannose but not N-acetyl-galactosamine, N-acetyl
      glucosamine, or maltose, though mannose-binding lectin (MBL) containing similar
      amino acid motif. CL-K1 can recognize specially several bacterial saccharides due
      to specific sugar-binding character. Elucidation of the role of two ancestor
      collectins of CL-K1 and CL-L1 could lead to see the biological function of
      collectin family.

PMID- 17179670
TI  - Pretreatment with N-nitro-L-arginine methyl ester improved oxygenation after
      inhalation of nitric oxide in newborn piglets with Escherichia coli pneumonia and
      sepsis.
AB  - We evaluated the effects of a combined therapy of pre-blockade endogenous nitric
      oxide synthase (NOS) with N-nitro-L-arginine methyl ester (L-NAME) and continuous
      inhaled NO (iNO) on the gas exchange and hemodynamics of Escherichia coli
      pneumonia and sepsis in newborn piglets. Seven to ten day old ventilated newborn
      piglets were randomized into 5 groups: control, E. coli pneumonia control,
      pneumonia with iNO 10 ppm, pneumonia pre-treated with L-NAME 10 mg/kg, and
      pneumonia with the combined therapy of L-NAME pretreatment and iNO. E. coli
      pneumonia was induced via intratracheal instillation of Escherichia coli, which
      resulted in progressively decreased cardiac index and oxygen tension; increased
      pulmonary vascular resistance index (PVRI), intrapulmonary shunting, and
      developed septicemia at the end of 6 hr experiment. iNO ameliorated the
      progressive hypoxemia and intrapulmonary shunting without affecting the PVRI.
      Only two of 8 animals with L-NAME pretreated pneumonia survived. Whereas when iNO
      was added to infected animals with L-NAME pretreatment, the progressive hypoxemia
      was abolished as a result of a decrease in intrapulmonary shunting without
      reverse of the high PVRI and systemic vascular resistance index induced by the L
      NAME injection. This result suggests that a NOS blockade may be a possible
      supportive option for oxygenation by iNO treatment in neonatal Gram-negative
      bacterial pneumonia and sepsis.

PMID- 17179671
TI  - Three-year follow-up of an outbreak of Serratia marcescens bacteriuria in a
      neurosurgical intensive care unit.
AB  - We report on the investigations and interventions conducted to contain an
      extended outbreak of Serratia marcescens bacteriuria that lasted for years in a
      neurosurgical intensive care unit (NSICU). A case-control study was performed to
      identify the risk factors for S. marcescens acquisition in urine. In case
      patients, urine sampling for tests and central venous catheterization were
      performed more frequently before the isolation of S. marcescens. Case patients
      were more frequently prescribed third-generation cephalosporins. Adherence to
      hand antisepsis was encouraged through in-service educational meetings and
      infection control measures, especially concerning the manipulation of indwelling
      urinary catheters, were intensified. The outbreak persisted despite the
      reinforcement of infection control measures. However, no patient has newly
      acquired the organism in the NSICU since December 2004. Multiple factors,
      including inadequate infection control practices and inappropriate antimicrobial
      usage, possibly contributed to the persistence of this S. marcescens outbreak.
      Healthcare workers should consistently follow infection control policies to
      ensure quality care.

PMID- 17179672
TI  - Lack of Toll-like receptor 4 and 2 polymorphisms in Korean patients with
      bacteremia.
AB  - Toll-like receptors (TLRs) are pattern-recognition receptors that are important
      in innate immune responses to bacterial infection. The purpose of this study is
      to describe the prevalence of TLRs genetic variations in the bacteremic patients
      in Korea. A total of 154 patients with bacteremia and 179 healthy volunteers were
      included. The Asp299Gly and Thr399Ile allele of the TLR4 gene and Arg753Gln and
      Arg677Trp allele of the TLR2 gene were tested by PCR-RFLP. The DNA sequences were
      determined to confirm the PCR-RFLP results. Contrary to the expectation, no
      genetic polymorphisms were detected in both groups of this study, suggesting that
      it is very rare in Korean.

PMID- 17179673
TI  - G and P genotyping of human rotavirus isolated in a university hospital in Korea:
      implications for nosocomial infections.
AB  - To characterize rotavirus G and P genotypes circulating among infants and young
      children hospitalized with severe diarrhea in a university hospital in Gyeonggi
      province, Korea, and to examine any association of the genotypes and nosocomial
      infections, we genotyped 103 isolates of rotavirus by multiplex RT-PCR. In July
      2001-June 2002, we found that globally common strains constituted 64.2% (G2P[4]
      28.3%, G3P[8] 28.3%, G4P[8] 5.7%, and G1P[8] 1.9%), and the uncommon strain,
      G4P[6], constituted 26.4%. During July 2002-June 2003, the percentage of common
      strains decreased to 44.0% (G3P[8] 18.0%, G2P[4] 16.8%, and G1P[8] 10.0%), but
      G4P[6] increased to 36.0%. G9P[8] was identified in 10.0% of cases, and thus can
      be considered an emerging strain in Korea. Eight-eight percent of G4P[6] was
      isolated from newborn babies. Among the 103 patients, there was an evidence of
      nosocomial rotavirus infection in 23 children (22.3%). Of these, 19 (82.6%) were
      newborns infected with G4P[6] strains of rotavirus. Most of the children who
      acquired rotavirus infection nosocomially showed symptoms of diarrhea, vomiting,
      fever, poor sucking, or dehydration, regardless of the genotype. This study
      revealed that G4P[6] has been the major genotype causing nosocomial rotavirus
      infection in our hospital.

PMID- 17179674
TI  - Complications of 2-D echocardiography guided transfemoral right ventricular
      endomyocardial biopsy.
AB  - Endomyocardial biopsy (EMBx) is a useful tool for diagnosing various cardiac
      pathologies. However, the routine use of EMBx has not gained widespread
      acceptance due to the possible complications related to the EMBx. Thus, not much
      information is available on the complications related to the EMBx. We
      prospectively evaluated 90 consecutive patients who underwent 2-D
      echocardiography guided transfemoral right ventricular EMBx at Kyungpook National
      University Hospital between March 2002 and November 2005 to determine the
      incidence, nature and subsequent management of complications related to EMBx. The
      clinical diagnoses before the EMBx were arrhythmogenic right ventricular
      dysplasia in 54, dilated cardiomyopathy in 19, Brugada syndrome in 9, myocarditis
      in 6 and miscellaneous in 2 patients. The overall major complication rate was
      5.6% and no procedure-related mortality occurred. Myocardial perforation (n=3),
      which was the most frequent complication, did not progress to cardiac tamponade
      requiring pericardiocentesis in any patient. Hemodynamically unstable ventricular
      tachycardia occurred in 1 patient. New and persistent right bundle branch block
      occurred in another. Our findings suggest that 2-D echocardiography guided
      transfemoral right ventricular EMBx is a relatively safe procedure.

PMID- 17179675
TI  - Causes of sudden death related to sexual activity: results of a medicolegal
      postmortem study from 2001 to 2005.
AB  - Sexual activity (SA), combined with organic heart disease, may cause sudden death
      (SD). However, the causes of SD related to SA are not known well. The aim of this
      study was to assess the causes of SD related to SA. From August 2001 to November
      2005, all autopsies (n=1,379) performed at Kyungpook National University were
      prospectively searched for SD cases related to SA. Fourteen cases (46+/-11 yr
      old, 9 males) of SD related to SA were found. All were heterosexual. The
      toxicologic study was negative in all. Ten cases were witnessed; during SA in 4
      cases, just after SA in another 4 cases, 2 and 5 hr after in 1 each case. In 4
      unwitnessed cases the victims were found dead less than 12 hr from the end of
      their SA. The partners were steady extramarital partners (n=8), prostitutes
      (n=2), marital partner (n=1) and unknown (n=3). The causes of the SD were as
      follows; coronary artery disease in 6, subarachnoid hemorrhage with ruptured
      berry aneurysm in 4, fibromuscular dysplasia of the atrioventricular nodal artery
      in 2, and unknown in 2. Coronary artery disease and subarachnoid hemorrhage with
      ruptured berry aneurysm were important as causes of SD related to SA.

PMID- 17179676
TI  - Cotransplanted bone marrow derived mesenchymal stem cells (MSC) enhanced
      engraftment of hematopoietic stem cells in a MSC-dose dependent manner in
      NOD/SCID mice.
AB  - Transplantation of marrow-derived mesenchymal stem cells (MSCs), expanded by
      culture in addition to whole bone marrow, has been shown to enhance engraftment
      of human hematopoietic stem cells (HSCs). Our hypothesis was that there might be
      an optimum ratio range that could enhance engraftment. We examined the percent
      donor chimerism according to the ratio of HSCs to MSCs in non-obese
      diabetic/severe combined immunodeficiency (NOD/SCID) mice. We tested a series of
      ratios of co-transplanted CD34(+) -selected bone marrow cells, and marrow-derived
      MSCs into sublethally irradiated NOD/SCID mice. In all experiments, 1x10(5) bone
      marrow derived human CD34(+) cells were administered to each mouse and human MSCs
      from different donors were infused concomitantly. We repeated the procedure three
      times and evaluated engraftment with flow cytometry four weeks after each
      transplantation. Serial ratios of HSCs to MSCs were 1:0, 1:1, 1:2 and 1:4, in the
      first experiment, 1:0, 1:1, 1:2, 1:4 and 1:8 in the second and 1:0, 1:1, 1:4, 1:8
      and 1:16 in the third. Cotransplantation of HSCs and MSCs enhanced engraftment as
      the dose of MSCs increased. Our results suggest that the optimal ratio of HSCs
      and MSCs for cotransplantation might be in the range of 1:8-1:16; whereas, an
      excessive dose of MSCs might decrease engraftment efficiency.

PMID- 17179678
TI  - Comparison of allergic indices in monosensitized and polysensitized patients with
      childhood asthma.
AB  - Monosensitization differs both immunologically and clinically from
      polysensitization, and specific immunotherapy is more effective in patients
      sensitized only to a single pollen than in multiple-pollen sensitized patients.
      To further examine the differences between monosensitized and polysensitized
      allergies, allergic indices were examined in 68 monosensitized and 62
      polysensitized patients with childhood asthma. Measurements included symptom
      scores, eosinophil counts, skin prick tests, serum total and specific IgE levels,
      and IL-10 levels, and were used to compare allergic indices between the two
      groups. Patients were followed for 18 months following immunotherapy to examine
      the effectiveness of the treatment. Symptom scores and total IgE levels were
      significantly higher in the polysensitized group than those in the monosensitized
      group (p<0.05). The levels of skin test response decreased significantly in both
      groups following immunotherapy. In the monosensitized group, symptom scores and
      specific IgE levels were significantly reduced after immunotherapy (p<0.05). In
      the polysensitized group, symptom scores were reduced after immunotherapy
      (p<0.05), but the degree of reduction was less than that of the monosensitized
      group (p<0.05). Moreover, in the polysensitized group, specific IgE levels after
      immunotherapy did not differ from that before immunotherapy. Serum IL-10 levels
      were not significantly increased after immunotherapy in either group. In
      conclusion, polysensitized patients tend to show higher allergic indices and
      immunotherapy might be less effective for these patients.

PMID- 17179677
TI  - IL-2 pathway blocking in combination with anti-CD154 synergistically establishes
      mixed macrochimerism with limited dose of bone marrow cells and prolongs skin
      graft survival in mice.
AB  - To facilitate the establishment of mixed chimerism with limited dose of bone
      marrow (BM) cells, and to achieve tolerance in skin graft model, combined
      blocking of costimulatory pathway and IL-2 pathway was used in minimally
      myeloablative model using busulfan. BM cells (2.5x10(7)) of BALB/c were injected
      into C57BL/6 mice at day 0 with full thickness skin graft after single dose
      injection of busulfan (25 mg/kg) on day-1. Recipients were grouped and injected
      the anti-CD154, CTLA4-Ig, anti-IL-2R at days 0, 2, 4, and 6 according to
      protocol. Mixed macrochimerism were induced in groups treated with anti
      CD154+anti-CTLA4-Ig, anti-CD154+anti-IL-2R, and anti-CD154+anti-CTLA4 Ig+anti-IL
      2R. Three groups having chimerism enjoyed prolonged graft survival more than 6
      months. Superantigen deletion study revealed deletion of alloreactive T cells in
      combined blockade treated groups. In graft versus host disease model using CFSE
      staining, CD4+ T cell and CD8+ T cell proliferation were reduced in groups
      treated with CTLA4-Ig or anti-IL-2R or both in combination with anti-CD154.
      However, anti-IL-2R was not so strong as CTLA4-Ig in terms of inhibition of T
      cell proliferation. In conclusion, IL-2 pathway blocking combined with anti-CD154
      can establish macrochimerism with limited dose of BM transplantation and induce
      specific tolerance to allograft.

PMID- 17179679
TI  - Main bronchial reconstruction with sparing of pulmonary parenchyma for benign
      diseases.
AB  - Main bronchial reconstruction is anatomically suitable for benign main bronchial
      stenosis. But, it has been hardly recommended for operative mortality and
      morbidity. This study was aimed at providing validity and the proper clinical
      information of bronchoplasty for benign main bronchial stenosis by reviewing the
      results we obtained over the last ten years for main bronchial reconstruction
      operations. We retrospectively reviewed admission and office records. Twenty
      eight consecutive patients who underwent main bronchoplasty were included.
      Enrolled patients underwent main bronchial reconstruction for benign disease
      (tuberculosis in 21, trauma in 4, endobronchial mass in 3). Concomitant
      procedures with main stem bronchoplasty were performed in 19 patients. There were
      no incidences of postoperative mortality and significant morbidity. There were 2
      cases of retained secretions, and these problems were resolved by bronchoscopy or
      intubation. All of the patients are still alive without obstructive airway
      problem. Bronchoplasty should be considered as one of the primary treatment
      modalities, if it is anatomically feasible.

PMID- 17179680
TI  - GSTM1 and GSTP1 polymorphisms as potential factors for modifying the effect of
      smoking on inflammatory response.
AB  - Inflammation has been known to be an important underlying condition for
      development of various diseases including cancer. The aims of this study were to
      investigate whether tobacco smoke exposure increases the level of inflammation
      biomarkers and the GSTM1 and GSTP1 gene polymorphisms are associated with
      inflammatory response due to tobacco smoke exposure. We measured urinary cotinine
      level in 300 healthy university students. Total serum TNF-alpha levels and blood
      WBC counts were determined to evaluate inflammatory response. Allelic loss of the
      GSTM1 and the GSTP1 (Ile105Val) polymorphism were determined by PCR and RFLP.
      Tobacco smoke exposure was found to be associated with increase of both TNF-alpha
      level and WBC count. Particularly, smokers with combination of GSTM1 null and
      GSTP1 AG or GG genotypes showed higher TNF-alpha level than those with the other
      genotype combinations (p=0.07). This result suggests that smoking may induce
      inflammation measured as TNF-alpha level or WBC count and combinations of the
      GSTM1 and GSTP1 polymorphisms may modify the effect of smoking on serum TNF-alpha
      level.

PMID- 17179681
TI  - The prevalence and evolution of anemia associated with tuberculosis.
AB  - Tuberculosis (TB) may produce abnormalities in the peripheral blood, including
      anemia. However, the evolution of TB-associated anemia with short-term
      combination anti-TB chemotherapy has not been well elucidated. The aim of this
      study was to characterize TB-associated anemia by clarifying its prevalence,
      characteristics, and evolution, through involving large numbers of patients with
      TB. The medical records of adult patients with TB diagnosed between June 2000 and
      May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on
      diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in
      only 45 patients (5.0%). Anemia was more frequently associated with the female
      and old age. Good treatment response, young age (< or =65 yr-old) and initial
      high hemoglobin were the predictive factor for resolution of anemia. In 202
      patients with anemia (71.9%), anemia was normocytic and normochromic. During or
      after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients
      without iron intake. The mean duration of resolution from the initiation of anti
      TB treatment was 118.8+/-113.2 days. In conclusion, anemia is a common
      hematological abnormality in patients with TB and close observation is sufficient
      for patients with TB-associated anemia, because TB-associated anemia is usually
      mild and resolves with anti-TB treatment.

PMID- 17179682
TI  - Mid-term outcomes of side-to-side stapled anastomosis in cervical
      esophagogastrostomy.
AB  - This study was conducted to evaluate the mid-term results of cervical
      esophagogastric anastomosis using a side-to-side stapled anastomosis method for
      treatment of patients with malignant esophageal disease. A total of 13 patients
      were reviewed retrospectively from January 2001 to November 2005 who underwent
      total esophagectomy through a right thoracotomy, gastric tube formation through a
      midline laparotomy and finally a cervical esophagogastric anastomosis. Average
      patient age was 62.6 yr old and the male to female ratio was 11:2. The mean
      anastomosis time was measured to be about 32.5 min; all patients were followed
      for about 22.8+/-9.9 months postoperatively. There were no early or late
      mortalities. There were no complications of anastomosis site leakage or conduit
      necrosis. A mild anastomotic stricture was noted in one patient, and required two
      endoscopic bougination procedures at postoperative 4th month. Construction of a
      cervical esophagogastric anastomosis by side-to-side stapled anastomosis is
      relatively easy to apply and can be performed in a timely manner. Follow up
      outcomes are very good. We, therefore, suggest that the side-to-side stapled
      anastomosis could be used as a safe and effective option for cervical
      esophagogastric anastomosis.

PMID- 17179683
TI  - Efficacy of two triple eradication regimens in children with Helicobacter pylori
      infection.
AB  - Triple therapy with bismuth subsalicylate, amoxicillin, metronidazole (BAM) or
      with omeprazole, amoxicillin, clarithromycin (OAC) has been commonly used for the
      eradication of Helicobacter pylori infection. We compared the efficacy of these
      triple therapies in children with H. pylori infection. We retrospectively
      analyzed results in 233 children with H. pylori infection and treated with OAC
      (n=141) or BAM (n=92). Overall eradication rates of triple therapy with OAC and
      BAM were 74% and 85%, respectively, which showed no statistical difference. Our
      study showed that the triple therapy with BAM was more effective for the first
      line eradication of H. pylori infection in Korean children, but has no
      statistical difference with OAC regimen.

PMID- 17179684
TI  - Analysis of endoscopic electronic image of intramucosal gastric carcinoma using a
      software program for calculating hemoglobin index.
AB  - Hemoglobin is the predominent pigment in the gastrointestinal mucosa, and the
      development of electronic endoscopy has made it possible to quantitatively
      measure the mucosal hemoglobin volume, by using a hemoglobin index (IHb). The
      aims of this study were to make a software program to calculate the IHb and then
      to investigate whether the mucosal IHb determined from the electronic endoscopic
      data is a useful marker for evaluating the color of intramucosal gastric
      carcinoma with regard to its value for discriminating between the histologic
      types. We made a software program for calculating the IHb in the endoscopic
      images. By using this program, the mean values of the IHb for the carcinoma (IHb
      C) and those of the IHb for the surrounding non-cancerous mucosa (IHb-N) were
      calculated in 75 intestinal-type and 34 diffuse-type intramucosal gastric
      carcinomas. We then analyzed the ratio of the IHb-C to the IHb-N (C/N ratio). The
      C/N ratio in the intestinal-type carcinoma group was higher than that in the
      diffuse-type carcinoma group (p<0.001). In the diffuse-type carcinoma group, the
      C/N ratio in the body was lower than that in the antrum (p=0.022). The accuracy
      rate, sensitivity, specificity, and the positive and negative predictive values
      for the differential diagnosis of the diffuse-type carcinoma from the intestinal
      type carcinoma were 94.5%, 94.1%, 94.7%, 88.9% and 97.3%, respectively. IHb is
      useful for making quantitative measurement of the endoscopic color in the
      intramucosal gastric carcinoma, and the C/N ratio by using the IHb would be
      helpful for distinguishing the diffuse-type carcinoma from the intestinal-type
      carcinoma.

PMID- 17179685
TI  - Cut-off values of visceral fat area and waist circumference: diagnostic criteria
      for abdominal obesity in a Korean population.
AB  - The aim of this study was to determine the appropriate cut-off values for
      visceral fat area and waist circumference (WC) associated with an increase in
      risk for obesity-related disorder, and to validate diagnostic criteria for
      abdominal obesity and the metabolic syndrome in a Korean adult population. We
      included 413 subjects (174 men and 239 women) for this study. Subjects were
      selected among Korean adults who visited the obesity clinic at St. Mary's
      Hospital and Kangnam St. Mary's Hospital from January 1999 to August 2005. All
      patients had computed tomography performed. The cut-off value, of visceral fat
      area associated with an increase risk of obesity-related disorder, according to
      the receiver operating characteristics curve, was 103.8 cm2 (sensitivity 74.5%,
      specificity 64.7%, p<0.001). The cut-off value for the WC was 89.8 cm in men
      (sensitivity 84.7%, specificity 91.7%, p<0.005) and 86.1 cm in women (sensitivity
      83.9%, specificity 62.9%, p<0.001). Based on the results of this study, the
      visceral fat area associated with an increased risk of obesity-related disorder
      in Korea was 103.8 cm2 and the WC was 89.8 cm in men and 86.1 cm in women.

PMID- 17179686
TI  - Cost is a barrier to widespread use of liquid-based cytology for cervical cancer
      screening in Korea.
AB  - This study aimed to document current cervical cancer screening practices of
      physicians in Korea. Questionnaires were distributed to 852 Korean obstetricians
      and gynecologists, who attended the 91st Conference of the Korean Society of
      Obstetrics and Gynecology held during May, 2005. Questionnaires were returned by
      30.6% (260/852) of the recipients and 254 of these were eligible for analysis.
      Sixty-seven percent started cervical cancer screening women at age 20, and 65%
      replied that they would continue annual screening in a 35-yr-old woman with three
      consecutive normal cytologic tests. Over 65% of respondents preferred
      conventional cytologic screening to liquid-based cytology. The cost was a major
      determinant for selecting screening method. Fifty-three percent used the human
      papillomavirus DNA test as a triage for atypical squamous cells of undetermined
      significance. Our findings suggest that majority of Korean obstetricians and
      gynecologists in hospital prefer annual conventional cytologic testing to liquid
      based cytology for financial reason.

PMID- 17179687
TI  - Effects of bladder training and/or tolterodine in female patients with overactive
      bladder syndrome: a prospective, randomized study.
AB  - We compared the effects of bladder training and/or tolterodine as first line
      treatment in female patients with overactive bladder (OAB). One hundred and
      thirty-nine female patients with OAB were randomized to treatment with bladder
      training (BT), tolterodine (To, 2 mg twice daily) or both (Co) for 12 weeks.
      Treatment efficacy was measured by micturition diary, urgency scores and
      patients' subjective assessment of their bladder condition. Mean frequency and
      nocturia significantly decreased in all treatment groups, declining 25.9% and
      56.1%, respectively, in the BT group; 30.2% and 65.4%, respectively, in the To
      group; and 33.5% and 66.3%, respectively in the Co group (p<0.05 for each). The
      decrease in frequency was significantly greater in the Co group than in the BT
      group (p<0.05). Mean urgency score decreased by 44.8%, 62.2% and 60.2% in the BT,
      To, and Co groups, respectively, and the improvement was significantly greater in
      the To and Co groups than in the BT group (p<0.05 for each). Although BT, To and
      their combination were all effective in controlling OAB symptoms, combination
      therapy was more effective than either method alone. Tolterodine alone may be
      instituted as a first-line therapy, but may be more effective when combined with
      bladder training.

PMID- 17179689
TI  - mRNA expression and RNA editing (2451 C-to-U) of IL-12 receptor beta2 in adult
      atopic patients.
AB  - Interleukin (IL)-12 activates T helper (Th) 1 cells to produce interferon (IFN)
      gamma which inhibits atopic inflammation. IL-12 acts through interaction with its
      receptor, especially beta(2) subunit. In several studies, the low production of
      IFN-gamma in peripheral mononuclear cells of atopic patients on response to IL-12
      stimulation has been reported. Therefore we investigated the IL-12 receptor
      beta(2) (IL-12R beta(2)) mRNA expression and RNA editing, nucleotide 2451 C-to-U
      conversion, to find the cause of low responsiveness to IL-12 in atopy.
      Quantitative real time PCR for mRNA expression and sequence analysis for RNA
      editing were performed in 80 atopic patients and 54 healthy controls. The
      expression of IL-12R beta(2) mRNA was significantly lower in atopic patients than
      healthy controls (p<0.05). In sequence analysis, RNA editing on nucleotide 2451
      was not found from either atopic patients or healthy controls. In additional
      evaluation, there was no relationship between expression of IL-12R beta(2) mRNA
      and serum total IgE or blood eosinophil count. Reduced IL-12R beta(2) mRNA
      expression in atopic patients indicate the reduced capacity to respond to IL-12
      which induce IFN-gamma production and this may contribute to Th2-skewed immune
      response in atopy.

PMID- 17179688
TI  - Cyclooxygenase-2 and inducible nitric oxide synthase expression in thyroid
      neoplasms and their clinicopathological correlation.
AB  - To evaluate the expressions of cyclooxygenase-2 (COX-2) and inducible nitric
      oxide synthase (iNOS) in thyroid neoplasms in a Korean population, we studied a
      total of 154 cases: papillary carcinoma of classical type (PTC), 86; follicular
      adenoma (FA), 21; follicular carcinoma (FC), 35; medullary carcinoma (MC), 3;
      undifferentiated carcinoma (UC), 5; and Hurthle cell neoplasm (HN), 4. Using
      immunohistochemical staining, COX-2 expression was detected in 62 (72.1%) PTC
      specimens, 5 (23.8%) FA specimens, 10 (28.6%) FC specimens, 0 (0.0%) MC
      specimens, 1 (20.0%) UC specimen, and 3 (75%) HN specimens. iNOS expression was
      detected in 66 (76.7%) PTC specimens, 4 (19.0%) FA specimens, 13 (37.1%) FC
      specimens, 0 (0.0%) MC specimens, 3 (60.0%) UC specimens, and 4 (100%) HN
      specimens. The results showed that COX-2 and iNOS were frequently expressed in
      the PTC and HN specimens, and iNOS was more frequently overexpressed in the FC
      specimens than in the FA specimens. In PTC, COX-2 and iNOS were significantly
      overexpressed in patients over 45 yr of age (p=0.029, p=0.041), and iNOS
      expression was increased in patients with a large primary tumor (p=0.028). These
      results suggest that the upregulation of COX-2 and iNOS may contribute to the
      tumor progression of thyroid gland, particularly in PTC and HN, and iNOS may play
      an adjuvant role during the tumor progression of FC.

PMID- 17179690
TI  - Association of the GSTP1 and NQO1 polymorphisms and head and neck squamous cell
      carcinoma risk.
AB  - The GSTP1 and NQO1 have been reported to be associated with an increased risk for
      smoking related head and neck squamous cell carcinoma (HNSCC). The purpose of
      this study was to determine the effect of these metabolic gene polymorphisms on
      the risk of HNSCC. The study population included 294 histologically confirmed
      HNSCC cases and 333 controls without cancer. Genotyping analysis of the GSTP1
      Ile105Val and NQO1 Trp139Arg genes was performed by polymerase chain reaction
      based techniques on DNA prepared from peripheral blood. The Mantel-Haenszel chi2
      test was used for statistical analysis. The allele frequencies of the GSTP1 and
      NQO1 polymorphisms were not statistically significant between cases and controls.
      In analyzing the association between smoking amounts and genetic polymorphisms,
      GSTP1 and NQO1 polymorphisms were associated with cigarette smoking amounts in
      cases. G allele containing genotypes in GSTP1 and T allele containing genotypes
      in NQO1 were associated with a tobacco dose-dependent increase in risk of HNSCC
      and these genotype distributions were statistically significant (p<0.05). We
      found that the GSTP1 105Val allele and NQO1 139Arg allele were associated with
      tobacco dose-dependent increase in risk of HNSCC. GSTP1 and NQO1 genotype
      polymorphisms may play an important role in the development of smoking related
      HNSCC.

PMID- 17179691
TI  - Single transconjunctival incision and two-point fixation for the treatment of
      noncomminuted zygomatic complex fracture.
AB  - The ultimate goal in treating zygomatic complex fracture is to obtain an
      accurate, stable reduction while minimizing external scars and functional
      deformity. The present authors present our experiences with a single
      transconjunctival incision and two-point (inferior orbital rim and
      frontozygomatic suture) fixation in 53 patients with zygomatic complex fracture
      which were not comminuted. All patients had transconjunctival approaches with
      lateral canthal extensions, and six out of 53 patients also had an additional
      small (about less than 2 cm) gingivobuccal incision to achieve an accurate
      reduction. There were 3 minor complications, and the overall esthetics and
      functional results were satisfactory with a long term follow-up. Our method has
      the following advantages in the reduction of zygomatic complex fracture; It
      leaves only an inconspicuous lateral canthal scar. In addition, it provides
      excellent simultaneous visualization of the inferior orbital rim and
      frontozygomatic suture area. Hence, two point fixation through a single incision
      can be performed with a satisfactory stability.

PMID- 17179692
TI  - A correlation between low back pain and associated factors: a study involving 772
      patients who had undergone general physical examination.
AB  - Many factors are associated with the development of low back pain. Among them,
      exercise, obesity, smoking, age, educational level and stress are the most
      common. This study examined the association of these factors with low back pain.
      An additional aim was to determine a procedure for preventing low back pain. This
      study analyzed the responses to a questionnaire sent to 772 individuals who had
      undergone a medical examination at this hospital in 2003 and excluded the
      individuals who had shown symptoms or their test results indicated a particular
      disease. Assuming that there were no variables, individuals who exercised
      regularly 3-4 times per week would have a lower chance of having low back pain
      than those who did not exercise regularly. The analysis revealed that individuals
      with a college degree or higher education have a lower chance of experiencing low
      back pain than those with only a high school education or even college drop-outs.
      When the other variables were constant, age, extent of obesity (body mass index),
      smoking and level of stress were not found to affect the development of low back
      pain. The level of education was associated with the development of low back
      pain. However, regular exercise 3-4 times per week or more would be most
      effective in reducing the incidence and duration of low back pain.

PMID- 17179693
TI  - Validation in the cross-cultural adaptation of the Korean version of the Oswestry
      Disability Index.
AB  - Disability questionnaires are used for clinical assessment, outcome measurement,
      and research methodology. Any disability measurement must be adapted culturally
      for comparability of data, when the patients, who are measured, use different
      languages. This study aimed to conduct cross-cultural adaptation in translating
      the original (English) version of the Oswestry Disability Index (ODI) into
      Korean, and then to assess the reliability of the Korean versions of the Oswestry
      Disability Index (KODI). We used methodology to obtain semantic, idiomatic,
      experimental, and conceptual equivalences for the process of cross-cultural
      adaptation. The KODI were tested in 116 patients with chronic low back pain. The
      internal consistency and reliability for the KODI reached 0.9168 (Cronbach's
      alpha). The test-retest reliability was assessed with 32 patients (who were not
      included in the assessment of Cronbach's alpha) over a time interval of 4 days.
      Test-retest correlation reliability was 0.9332. The entire process and the
      results of this study were reported to the developer (Dr. Fairbank JC), who
      appraised the KODI. There is little evidence of differential item functioning in
      KODI. The results suggest that the KODI is internally consistent and reliable.
      Therefore, the KODI can be recommended as a low back pain assessment tool in
      Korea.

PMID- 17179694
TI  - Validation study of tripartite model of anxiety and depression in children and
      adolescents: clinical sample in Korea.
AB  - Although the currently available literature has provided some empirical support
      for a tripartite model of child and adolescent anxiety and depression, one of the
      limitations of these studies was that they have been conducted in America,
      primarily with Caucasians. In order to make this model more applicable to diverse
      ethnic and cultural groups, this study used a tripartite model for child and
      adolescent anxiety and depression in Korea, using confirmatory factor analysis
      with logically selected items from the Revised Children's Manifest Anxiety Scale
      (RCMAS), as well as the Children's Depression Inventory (CDI). The results
      indicated that the model fit of a three-factor model was superior to one- and two
      factor models. In addition, the findings of discriminant analysis demonstrated
      that the correct classification rate with three factors of the tripartite model
      was superior to the classification rate achievable using CDI and RCMAS. In a
      departure from Clark and Watson's hypothesis, however, the correlations of three
      factors were significantly higher than had been expected. The results are
      discussed on the basis of cultural background.

PMID- 17179695
TI  - Adaptive responses induced by low dose radiation in dentate gyrus of rats.
AB  - The purpose of this study is to investigate the mechanism of alternative
      responses to low dose irradiation for neuronal cell proliferation in the dentate
      gyrus of rats. To determine the effect of a single exposure to radiation, rats
      were irradiated with a single dose of 0.1, 1, 10 or 20 Gy. To determine the
      effect of the cumulative dose, the animals were irradiated daily with 0.01 Gy or
      0.1 Gy from 1 to 4 days. The neuronal cell proliferation was evaluated using
      immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU), Ki-67 and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining.
      Four consecutive daily irradiations with a 0.01 Gy/fraction increased the number
      of BrdU-positive and Ki-67-positive cells in a dose dependent manner, but this
      did not affect the number of TUNEL-positive cells. However, there was not a dose
      dependent relationship for the 0.1 Gy/fraction irradiation with the number of
      BrdU, Ki-67 and TUNEL positive cells. Our data support the explanation that the
      adaptive response, induced by low-dose radiation, in the hippocampus of rats is
      more likely a reflection of the perturbations of cell cycle progression.

PMID- 17179696
TI  - A case of hypersensitivity syndrome to both vancomycin and teicoplanin.
AB  - Drug hypersensitivity syndrome to both vancomycin and teicoplanin has not been
      previously reported. We describe here a 50-yr-old male patient with vertebral
      osteomyelitis and epidural abscess who developed hypersensitivity syndrome to
      both vancomycin and teicoplanin. Skin rash, fever, eosinophilia, interstitial
      pneumonitis, and interstitial nephritis developed following the administration of
      each drug, and resolved after withdrawing the drugs and treating with high dose
      corticosteroids. The vertebral osteomyelitis was successfully treated with 6-week
      course of linezolid without further complications. Skin patch tests for
      vancomycin and teicoplanin was done 2 months after the recovery; a weak positive
      result for vancomycin (10% aq.,+at D2 and +at D4 with erythema and vesicles;
      ICDRG scale), and a doubtful result for teicoplanin (4% aq.-at D2 and+/-at D4
      with macular erythema; ICDRG scale). We present this case to alert clinicians to
      the hypersensitivity syndrome that can result from vancomycin and teicoplanin,
      with possible cross-reactivity, which could potentially be life-threatening.

PMID- 17179697
TI  - Spontaneous closure of iatrogenic coronary artery fistula to left ventricle after
      septal myectomy for hypertrophic obstructive cardiomyopathy.
AB  - Cases of iatrogenic coronary artery fistulas draining into the left ventricle
      after surgical myectomy for hypertrophic obstructive cardiomyopathy have been
      published as sporadic reports. However, its management scheme and prognosis are
      not clear because of the low incidence. A 46-yr-old woman was hospitalized for
      evaluation of chest pain and shortness of breath for 3 months. Transthoracic
      echocardiographic examination showed typical hypertrophic obstructive
      cardiomyopathy with a peak pressure gradient of 71 mmHg across the left
      ventricular outflow tract. The patient underwent surgical septal myectomy.
      Postoperative color Doppler imaging revealed a diastolic blood flow from the
      interventricular septal myocardium to the left ventricular cavity, i.e.
      iatrogenic coronary artery fistula to the left ventricle. Ten days later, the
      fistula closed spontaneously which was diagnosed by transthoracic
      echocardiography and confirmed by coronary angiography.

PMID- 17179698
TI  - A patient with mixed type Evans syndrome: efficacy of rituximab treatment.
AB  - Mixed type Evans syndrome is a very rare hematologic disease. Although mixed type
      Evans syndrome may initially respond well to steroids, this disease usually runs
      a chronic course with intermittent exacerbations. We describe here a 46-yr-old
      female with the steroid-refractory, mixed type Evans syndrome, and she had a
      prompt response to rituximab. She was diagnosed as having the mixed type Evans
      syndrome with the clinical features of symptomatic anemia, jaundice and
      thrombocytopenia. Prednisone therapy was commenced and her hemoglobin and
      platelet level returned to the normal. However, after 15 weeks, she relapsed with
      hemolytic anemia and thrombocytopenia. We started rituximab at the dose of 375
      mg/m(2) once weekly for a total of 4 doses, which was well-tolerated and this
      induced the normalization of hemoglobin, bilirubin and lactic dehydrogenase, and
      there was also a significant increase of the platelet count.

PMID- 17179699
TI  - Plasma cell granuloma associated with pulmonary actinomycosis: a case report.
AB  - Plasma cell granuloma (PCG) of the lung is a rare disease that usually presents
      as a pulmonary nodule or mass on incidental radiographic examination without
      symptoms. Although the etiology of PCG is still controversial, many findings have
      lent support to the lesion being a reactive inflammatory process rather than a
      neoplastic one. We describe a 53-yr-old male who presented with a hemoptysis and
      have a lung mass at the left upper lobe on chest radiograph. The lung mass was
      primarily diagnosed as PCG by percutaneous needle aspiration and biopsy, and the
      patient was treated with oral steroid because he and relatives refused the
      operation. However, the size of the lung mass did not change and open thoracotomy
      and lobectomy were done therefore. He was confirmed as having pulmonary
      actinomycosis with PCG after surgery. To our knowledge, this is the first report
      of PCG associated with actinomycosis in Korea.

PMID- 17179700
TI  - A case of renal crisis in a Korean scleroderma patient with anti-RNA polymerase I
      and III antibodies.
AB  - Scleroderma (SSc) renal crisis has been reported to be associated with anti-RNA
      polymerase I and III (RNAP I/III) antibodies in Caucasians and the Japanese.
      However, no report is available for Korean SSc patients. Here, we describe the
      case of a 65-yr-old female SSc patient who developed renal crisis and whose serum
      contained anti-RNAP I/III antibodies. She was finally diagnosed as having diffuse
      cutaneous SSc based on skin thickening proximal to the elbows and knees. Sudden
      hypertension, oliguria, and pulmonary edema were features of her renal crisis.
      Despite the use of captopril and adequate blood pressure control, her renal
      function deteriorated. Subsequent renal biopsy findings showed severe fibrinoid
      necrosis with luminal obliteration in interlobar arteries and arterioles
      consistent with SSc renal crisis. Serum anti-RNAP I/III antibodies were detected
      by radioimmunoprecipitation. This is the first report of a renal crisis in a
      Korean SSc patient with RNAP I/III antibodies.

PMID- 17179701
TI  - Macrophage activation syndrome in juvenile rheumatoid arthritis successfully
      treated with cyclosporine A: a case report.
AB  - Macrophage activation syndrome (MAS) is one of the serious complications of
      juvenile rheumatoid arthritis (JRA) and recently, cyclosporine A has been found
      to be effective in patients with corticosteroid-resistant MAS. A 29-yr-old male
      was admitted with high fever and jaundice for one month. He was diagnosed as
      juvenile arthritis 16 yr ago. Physical and laboratory results showed
      hepatosplenomegaly, high fever, pancytopenia and impaired liver and renal
      function tests, elevated triglyceride and serum ferritin levels. Bone marrow
      biopsy showed hyperplasia of histiocytes with active hemophagocytosis. He was
      diagnosed as MAS associated with juvenile rheumatoid arthritis and managed with
      high-dose corticosteroids initially, but clinical symptoms and laboratory
      findings did not improve immediately. Finally, he completely recovered after
      treatment with cyclosporine A (3 mg/kg/day).

PMID- 17179702
TI  - Idiopathic palmar fasciitis with polyarthritis syndrome.
AB  - A 31-yr-old Korean woman was presented with 4-month history of bilateral hand
      swelling and stiffness. On clinical examination, she had a painful synovitis of
      both hands, wrists, knees and ankles. The radiologic and histological
      examinations confirmed it with palmar fasciitis and polyarthritis syndrome
      (PFPAS). PFPAS is an uncommon disorder characterized by progressive flexion
      contractures of both hands, inflammatory fasciitiis, fibrosis, and a generalized
      inflammatory arthritis. Although most reported cases of PFPAS have been
      associated with various malignancies, our patient have not been associated with
      malignancy during 24 months follow up period from her first symptom onset. Her
      symptoms were improved with moderate dose of corticosteroid and she is currently
      taking prednisone 5 mg daily without any evidence for internal malignancy. We
      present here in a young Korean patient with idiopathic PFPAS who was successfully
      treated with administration of corticosteroid.

PMID- 17179703
TI  - Tethered spinal cord with double spinal lipomas.
AB  - Although lumbosacral lipoma is reported to occur in 4-8 of 100,000 patients, and
      66% of lipomyelomeningoceles in young patients are accompanied by hypertrophic
      filum terminale, it is very rare to find two isolated spinal lipomas
      simultaneously. A 3 month-old baby girl was admitted to the hospital for a
      protruding, non-tender, soft, subcutaneous 2.5 cm mass of the lumbosacral area
      that had been present since birth. Simple radiography showed a spinal posterior
      arch defect from L3 to L5, and magnetic resonance imaging (MRI) demonstrated two
      isolated spinal lipomas, a transitional type from L3 to L5, and a terminal type
      below S1 without dural defect. The cornus medullaris was severely tethered
      descending to the S1, but there was no cerebellar or brain stem herniation on the
      MRI. We suggest that the presence of a combined spinal lipoma should be a point
      for careful differentiation in an infant with spinal lipoma.

PMID- 17179704
TI  - Schwannomatosis involving peripheral nerves: a case report.
AB  - Schwannomatosis or neurilemmomatosis has been used to describe patients with
      multiple nonvestibular schwannomas with no other stigmata of neurofibromatosis
      type-2 (NF-2). In our case, schwannomatosis, multiple schwannomas were present in
      a 21-yr-old woman with no stigmata or family history of NF-1 or NF-2. She had no
      evidence of vestibular schwannoma or other intracranial tumors. Multiple
      peripheral tumors were found in the carotid space of the neck, and soft tissue of
      posterior shoulder, lower back, ankle and middle mediastinum. All of those tumors
      were completely limited to the right side of the body. All surgically removed
      tumor specimens in this patient proved to be schwannomas.

PMID- 17179705
TI  - Reliability and validity of the Korean Cancer Pain Assessment Tool (KCPAT).

PMID- 17179706
TI  - The effects of carbamazepine, valproic acid and phenobarbital on the oxidative
      and antioxidative balance in epileptic children.
AB  - BACKGROUND: Oxidative stress has been related in a wide variety of ways with
      nervous tissue. We studied the effect of antiepileptic monotherapy on serum level
      of total antioxidant capacity, lipid hydroperoxide, total peroxide, oxidative
      stress index, and individual serum antioxidants such as albumin, bilirubin and
      uric acid. PATIENTS AND METHODS: We studied 122 subjects including healthy
      controls, untreated epileptic patients and epileptic patients treated with
      valproic acid, carbamazepine or phenobarbital. Serum total antioxidant capacity
      was measured as an index of antioxidants, and total peroxide was measured as
      index of oxidative stress. The serum concentrations of uric acid, albumin,
      bilirubin and lipid hydroperoxide were monitored simultaneously. RESULTS: We
      found that serum total antioxidant capacity levels were significantly decreased
      in the untreated group compared with the controls. Serum total peroxide levels
      were markedly increased in the untreated and carbamazepine-treated groups
      compared to in the controls; and lipid hydroperoxide and oxidative stress index
      levels were significantly higher in the phenobarbital-treated group than in the
      controls. Uric acid concentrations were significantly lower in the valproic-acid
      treated group than in the untreated group, and total bilirubin concentrations
      were higher in the untreated group than in the controls. CONCLUSION: Epileptic
      children exposed to oxidative stress and conventional antiepileptic drugs change
      the oxidative/antioxidative balance. The serum oxidant and antioxidant status of
      epileptic children with valproic acid monotherapy are better regulated compared
      with children with carbamazepine and phenobarbital monotherapy.

PMID- 17179707
TI  - Brain lesions on MRI in elderly patients with type 2 diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus (DM) type 2 has been associated with
      poor cognitive performance and dementia, particularly in elderly patients. The
      exact mechanisms underlying the cognitive dysfunction in DM remain unclear.
      Imaging studies of the brain could be helpful to give more insight into possible
      structural brain lesions underlying these cognitive dysfunctions. Therefore, we
      performed a study in independently living patients with DM type 2 in order to
      investigate the association between DM and brain imaging abnormalities. METHODS:
      The study population consisted of 45 patients with DM type 2 without hypertension
      (mean age 73.4 +/- 5.1 years, mean duration 16.5 +/- 11.5 years), 45 patients
      with DM type 2 and hypertension (mean age 73.5 +/- 6.1 years, mean duration 11.9
      +/- 9.2 years) and 44 control subjects (mean age 73.1 +/- 5.4 years). All
      patients and control subjects underwent an MRI of the brain. White matter lesions
      (WML), cerebral atrophy and medial temporal lobe atrophy were rated by a
      standardized visual rating scale. Lacunar infarcts were defined as focal hypo
      intensities on fluid-attenuated inversion recovery sequences with a hyperintense
      rim around it. RESULTS: WML occurred more frequently in diabetic patients with
      hypertension as well as without hypertension. Significantly more deep WML were
      found in DM patients with and without hypertension when compared to control
      subjects, whereas no difference was found in the occurrence of periventricular
      hyperintensities. In all 3 groups, lacunar infarcts occurred sporadically. A
      trend towards higher atrophy scores was seen in patients with DM compared to
      control subjects. CONCLUSIONS: The data of this cross-sectional study suggest
      that type 2 DM is an independent risk factor for deep WML in the independently
      living elderly patients.

PMID- 17179708
TI  - Prognostic value of hyperintense vessel signals on fluid-attenuated inversion
      recovery sequences in acute cerebral ischemia.
AB  - BACKGROUND: Fluid-attenuated inversion recovery (FLAIR) sequences may reveal
      hyperintense vessel signals (HVS) at the acute stage of cerebral ischemia. The
      aim of this study was to test the hypothesis that HVS are associated with a worse
      outcome. METHODS: We included 30 consecutive patients admitted within 12 h after
      onset of hemispheric cerebral ischemia. The outcome was assessed with the
      modified Rankin Scale at month 1. RESULTS: Proximal HVS were present in 9
      patients and distal HVS in 16. All patients with proximal occlusions on time-of
      flight sequences had distal HVS on FLAIR. Patients with poor outcome at month 1
      (modified Rankin Scale 3-6) more frequently had had HVS on MRI (12/13 vs. 4/17;
      p< 0.001). CONCLUSION: Distal HVS found on FLAIR sequences within 12 h of acute
      cerebral ischemia are associated with a worse 1-month outcome.

PMID- 17179709
TI  - Wilson's disease: a great masquerader.
AB  - BACKGROUND: Wilson's disease (WD) is a treatable autosomal recessive metabolic
      disorder which could lead to protean hepatic or neurologic manifestations. WD
      could mimic many neurologic disorders and is often diagnosed with a long delay.
      This study describes central nervous system manifestations of a group of Iranian
      patients with neurologic WD. METHODS: Data from case records of patients with
      neurologic WD presenting at a referral university hospital and a private clinic
      in Tehran from 1984 to 2004 were analyzed. RESULTS: Fifty patients from 44
      unrelated families with WD were identified, whose mean duration of follow-up was
      51.8 (+/-58.5) months. The median age of onset of neurologic symptoms in 37
      patients with primary neurologic or simultaneous hepatic-neurologic presentation
      was 16 (10-38) years, whereas in 13 patients with prior hepatic damage, this was
      18.5 (11-34) years. The 6 most common manifestations were dysarthria (80%),
      drooling (48%), tremor in limbs (44%), abnormal gait (44%), psychiatric and/or
      sleep symptoms (44%), and dystonia in limbs (42%). CONCLUSION: Neurologic WD has
      heterogeneous manifestations and should be considered in young patients
      presenting with dysarthria, drooling, any kind of movement disorders or
      psychiatric symptoms.

PMID- 17179710
TI  - Contribution of nerve biopsy to unclassified neuropathy.
AB  - OBJECTIVES: To evaluate the diagnostic yield of nerve biopsy in patients with
      peripheral neuropathy of undetermined cause despite extensive diagnostic workup.
      METHODS: From November 2001 through January 2004, 38 patients underwent nerve
      biopsy because of unclassified neuropathy. RESULTS: The etiology of the
      neuropathies could be defined in 14 patients (37%), i.e. in 15% of chronic
      symmetric, 30% of chronic asymmetric, 50% of subacute symmetric and 62.5% of
      subacute asymmetric neuropathies. The biopsy was diagnostic in 6 patients (16%),
      where it showed a vasculitis, and supportive in 8 patients (21%). CONCLUSIONS:
      The contribution of nerve biopsy to the diagnosis of peripheral neuropathy was
      highest in acute and subacute asymmetric forms of neuropathy and lowest in
      chronic symmetric forms. The main indication for nerve biopsy remains the
      diagnosis of vasculitic neuropathy, a potentially treatable disorder.

PMID- 17179711
TI  - Hypertension and sensorimotor peripheral neuropathy in type 2 diabetes.
AB  - BACKGROUND: The mechanisms responsible for the onset of sensorimotor peripheral
      diabetic neuropathy (SMPN) remain largely unknown. To address this issue, we
      studied the relationship between traditional cardiovascular risk factors,
      parameters of metabolic control, and the presence of SMPN in patients with type 2
      diabetes of relatively short duration. METHODS: Blood pressure, glycated
      hemoglobin, lipid profile, and the presence of micro- and macrovascular
      complications were assessed and monitored in 31 consecutive ambulatory patients
      with type 2 diabetes (age 60.7 +/- 7.5 years, mean +/- SD) within 10 years of
      diagnosis (mean diabetes duration 6.0 +/- 2.3 years). RESULTS: Clinical and
      neurophysiological features of SMPN were present in 10 patients (SMPN+, 32%).
      There were no significant differences in age, gender distribution, diabetes
      duration, body mass index, metabolic control, and serum cholesterol between SMPN-
      and SMPN+ patients. However, the prevalence of hypertension (i.e. blood pressure
      >/=140/90 mm Hg) was higher in SMPN+ patients (10/10 vs. 13/21, chi(2 =) 5.13, p
      = 0.025). Regression analysis showed that, after correcting for age, gender,
      duration of diabetes, glycated hemoglobin, and cholesterol, the presence of
      hypertension was independently associated with SMPN (R(2) = 0.17, p = 0.023).
      CONCLUSIONS: There is a strong association between hypertension and SMPN in type
      2 diabetic patients with relatively short duration of disease. This relationship
      is independent of other risk factors.

PMID- 17179712
TI  - A new subtype classification of ischemic stroke based on treatment and etiologic
      mechanism.
AB  - A new subtype classification of ischemic stroke was developed to reflect recent
      therapeutic strategies as well as evolving concepts of stroke definitions and
      mechanisms. In 200 consecutive patients with acute ischemic stroke, the inter
      rater reliability and proportion of subtypes of the new classification system
      were assessed and compared with those of the Trial of ORG 10172 in the Acute
      Stroke Treatment (TOAST) classification. The most frequent subtype of the new
      classification was atherothrombosis (n = 80, 40%), followed by stroke of
      undetermined etiology (n = 54, 27%), small artery disease (n = 33, 16.5%),
      cardioembolism (n = 26, 13%), and stroke of other determined etiology (n = 7,
      3.5%). Three raters agreed to the stroke subtype diagnosis in 165 out of 200
      cases and the overall kappa value was excellent (kappa = 0.82). The new
      classification system for brain infarction was easy to use and had high inter
      rater reliability.

PMID- 17179713
TI  - Cerebral amyloid angiopathy with symptomatic or occult subarachnoid haemorrhage.

PMID- 17179714
TI  - Co-occurrence of astasia and unilateral asterixis caused by acute mesencephalic
      infarction.

PMID- 17179715
TI  - Thrombosis of internal carotid artery after cisplatin-based chemotherapy.

PMID- 17179716
TI  - Encephalitis of unknown etiology with anti-GluR epsilon2 autoantibody, showing
      divergent neuroradiologic and clinical findings.

PMID- 17179717
TI  - Phenotype variant of the common duplication at 17p11.2.

PMID- 17179718
TI  - New-onset Tourette syndrome following human growth hormone therapy.

PMID- 17179719
TI  - Burton's line in lead poisoning.
AB  - Lead poisoning in both its acute and chronic forms has been recognised since the
      second century BCE. Lead colic, anaemia, renal tubulopathies and motor
      neuropathies are well recognised. This paper sketches the early history and
      remembers the important contribution of Henry Burton, who described the gums to
      be bordered by a narrow leaden-blue line, about the one-twentieth part of an inch
      in width, whilst the substance of the gum apparently retained its ordinary colour
      and condition. The sign though inconstant, is still a valuable clinical clue.

PMID- 17179720
TI  - Synaesthesia.
AB  - Synaesthesia is the intriguing, involuntary experience of feeling one sensation
      in response to a different sensory stimulus. Recognised since described in 1890
      by John Locke and clarified by Galton in the 1880s, it has been analysed in the
      last 50 years. Grapheme-colour synaesthesia is the commonest form, but many other
      sensory linkages are reported. Experiments show that it is a genuine immediate
      perception, not merely a memory or learned association. Many of the mechanisms
      posited are based on indirect methods, and we know little of the
      neurophysiological mechanisms.

PMID- 17179721
TI  - Valetudinarian.

PMID- 17179722
TI  - Amnesia.

PMID- 17179723
TI  - Prognostic relevance of early MRI vessel signs is highly overrated--part 2.

PMID- 17179724
TI  - Fragmented pictures revisited: long-term changes in repetition priming, relation
      to skill learning, and the role of cognitive resources.
AB  - BACKGROUND: Whereas age-related declines in declarative memory have been
      demonstrated in multiple cross-sectional and longitudinal studies, the effect of
      age on non-declarative manifestations of memory, such as repetition priming and
      perceptual skill learning, are less clear. The common assumption, based on cross
      sectional studies, is that these processes are only mildly (if at all) affected
      by age. OBJECTIVE: To investigate long-term changes in repetition priming and age
      related differences in identification of fragmented pictures in a 5-year
      longitudinal design. METHOD: Healthy adults (age 28-82 years) viewed drawings of
      objects presented in descending order of fragmentation. The identification
      threshold (IT) was the highest fragmentation level at which the object was
      correctly named. After a short interval, old pictures were presented again along
      with a set of similar but novel pictures. Five years later the participants
      repeated the experiment. RESULTS: At baseline and 5-year follow-up alike, one
      repeated exposure improved IT for old (priming) and new (skill acquisition)
      pictures. However, long-term retention of priming gains was observed only in
      young adults. Working memory explained a significant proportion of variance in
      within-occasion priming, long-term priming, and skill learning. CONCLUSION:
      Contrary to cross-sectional results, this longitudinal study suggests perceptual
      repetition priming is not an age-invariant phenomenon and advanced age and
      reduced availability of cognitive resources may contribute to its decline.

PMID- 17179725
TI  - Molecular genetic analysis of normosmic hypogonadotropic hypogonadism in a
      Turkish population: identification and detailed functional characterization of a
      novel mutation in the gonadotropin-releasing hormone receptor gene.
AB  - BACKGROUND/AIMS: Currently known mutations account for less than 15% of cases
      with normosmic hypogonadotropic hypogonadism (nIHH). The objective of the study
      was to identify novel hereditary associations in the pathogenesis of nIHH.
      METHODS: We investigated 26 Turkish patients with nIHH (21 males and 5 females)
      from 22 families. The coding regions of the GnRH receptor, GnRH1, GPR54, and
      KISS1 genes were directly sequenced. RESULTS: In two sisters, a novel homozygous
      missense mutation, R139C, located in the conserved DRS motif at the junction of
      the third transmembrane and the second intracellular loop of the GnRH receptor
      was identified. The R139C mutation almost completely abolished plasma membrane
      expression while having little effect on GnRH-binding affinity. The mutant
      receptor expression was rescued by a membrane-permeant, non-peptide GnRH receptor
      antagonist IN3. CONCLUSIONS: Consistent with the previous studies we were able to
      find mutations in only 7.6% of a well-defined group of patients with nIHH, which
      further suggests that yet unidentified genetic associations to explain nIHH
      exist.

PMID- 17179726
TI  - Candidate-gene association study of mothers with pre-eclampsia, and their
      infants, analyzing 775 SNPs in 190 genes.
AB  - Pre-eclampsia (PE) affects 5-7% of pregnancies in the US, and is a leading cause
      of maternal death and perinatal morbidity and mortality worldwide. To identify
      genes with a role in PE, we conducted a large-scale association study evaluating
      775 SNPs in 190 candidate genes selected for a potential role in obstetrical
      complications. SNP discovery was performed by DNA sequencing, and genotyping was
      carried out in a high-throughput facility using the MassARRAY(TM) System. Women
      with PE (n = 394) and their offspring (n = 324) were compared with control women
      (n = 602) and their offspring (n = 631) from the same hospital-based population.
      Haplotypes were estimated for each gene using the EM algorithm, and empirical p
      values were obtained for a logistic regression-based score test, adjusted for
      significant covariates. An interaction model between maternal and offspring
      genotypes was also evaluated. The most significant findings for association with
      PE were COL1A1 (p = 0.0011) and IL1A (p = 0.0014) for the maternal genotype, and
      PLAUR (p = 0.0008) for the offspring genotype. Common candidate genes for PE,
      including MTHFR and NOS3, were not significantly associated with PE. For the
      interaction model, SNPs within IGF1 (p = 0.0035) and IL4R (p = 0.0036) gave the
      most significant results. This study is one of the most comprehensive genetic
      association studies of PE to date, including an evaluation of offspring genotypes
      that have rarely been considered in previous studies. Although we did not
      identify statistically significant evidence of association for any of the
      candidate loci evaluated here after adjusting for multiple testing using the
      false discovery rate, additional compelling evidence exists, including multiple
      SNPs with nominally significant p values in COL1A1 and the IL1A region, and
      previous reports of association for IL1A, to support continued interest in these
      genes as candidates for PE. Identification of the genetic regulators of PE may
      have broader implications, since women with PE are at increased risk of death
      from cardiovascular diseases later in life.

PMID- 17179728
TI  - FOLFOX-4 stop and go and capecitabine maintenance chemotherapy in the treatment
      of metastatic colorectal cancer.
AB  - OBJECTIVE: Patients with metastatic colorectal cancer (MCC) usually receive
      FOLFOX-4, or other oxaliplatin (L-HOP)-based regimens, until the occurrence of
      progressive disease, with an increase in the incidence of neurotoxicity which is
      correlated to the cumulative dose of L-HOP. The aim of this study was to evaluate
      if FOLFOX-4 stop and go and capecitabine maintenance chemotherapy is associated
      with a low incidence of severe neurotoxicity in the treatment of MCC patients.
      METHODS: Thirty-three patients were treated with FOLFOX-4 (L-HOP 85 mg/m(2) day
      1, leucovorin 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) and 22 h 600 mg/m(2)
      days 1 and 2, every 2 weeks). Patients who achieved objective response (OR) or
      stable disease (SD) then received oral capecitabine 2,500 mg/m(2) days 1-14 every
      3 weeks; L-HOP was reintroduced as soon as progression occurred. RESULTS: Twenty
      eight of the 29 patients who achieved OR or SD then received capecitabine. FOLFOX
      4 was reintroduced in 18 patients (56.2%). The median response duration (RD) was
      9.2 months and median progression-free survival (PFS) was 8.6 months. Twenty
      eight patients (87.5%) had peripheral neuropathy during treatment, but grade 3
      neurotoxicity was observed in only 1 patient (3.1%). CONCLUSIONS: FOLFOX-4 stop
      and go and capecitabine maintenance chemotherapy was associated with a very low
      incidence of grade 3 neurotoxicity. Although the number of patients enrolled was
      far too low for a definite conclusion, RD and PFS were comparable to those
      usually reported in the treatment of MCC patients.

PMID- 17179729
TI  - Fatigue assessment questionnaire: standardization of a cancer-specific instrument
      based on the general population.
AB  - OBJECTIVES: Fatigue has become a major issue of concern in the care of cancer
      patients, as it has been shown to compromise their quality of life in a
      significant and lasting way. However, there is a lack of economic and specific
      measures. The Fatigue Assessment Questionnaire (FAQ) has been developed based on
      thorough interviews and tested on a large mixed sample of cancer patients. The
      purposes of this paper are to test the psychometric properties of the FAQ and to
      provide norms for the German population. METHODS: The FAQ was administered to a
      representative sample of the German population (1,340 female and 1,101 male
      participants) along with standardized scales of depression, mood and life
      satisfaction. RESULTS: We could confirm that fatigue is multidimensional and can
      be measured by the scales of physical, affective and cognitive fatigue with good
      reliability and validity. The dependency of fatigue on sex and age makes it
      useful to have standard fatigue scores for oncological research as provided in
      this paper. CONCLUSION: The FAQ is a promising, differentiated, yet economic
      instrument for further use in oncological research.

PMID- 17179727
TI  - Subsets of Finns with high HDL to total cholesterol ratio show evidence for
      linkage to type 2 diabetes on chromosome 6q.
AB  - OBJECTIVES: The purpose of this study was to examine carefully heterogeneity
      underlying evidence for linkage to type 2 diabetes (T2DM) on chromosome 6q from
      two sets of FUSION families. METHODS: Ordered subsets analysis (OSA) was
      performed on two sets of FUSION families. For OSA results showing significant
      improvement in evidence for linkage, T2DM-related phenotypes were compared
      between individuals with T2DM within the subset versus the complement. RESULTS:
      OSA analysis revealed 105 families with the highest average HDL to total
      cholesterol ratio (HDL ratio) that had strongly increased evidence for linkage
      (MLS = 7.91 at 78.0 cM; uncorrected p = 0.00002). Subjects with T2DM within this
      subset were significantly leaner, had lower fasting glucose, insulin, and C
      peptide, and more favorable cardiovascular risk profile compared to the
      complement set of subjects with T2DM. OSA also revealed 33 families with the
      lowest average fasting insulin that had increased evidence for linkage at a
      second locus (MLS = 3.45 at 128 cM; uncorrected p = 0.017) coincident with
      quantitative trait locus linkage analysis results for fasting and 2-hour insulin
      in subjects without T2DM. CONCLUSIONS: These results suggest two diabetes
      susceptibility loci on chromosome 6q that may affect subsets of individuals with
      a milder form of T2DM.

PMID- 17179730
TI  - Single-agent gemcitabine for biliary tract cancers. Study outcomes and systematic
      review of the literature.
AB  - OBJECTIVE: The aim of this study was to investigate the outcomes of gemcitabine
      treated patients with inoperable biliary tract cancers. METHODS: We conducted a
      retrospective study of consecutively treated 22 inoperable biliary tract cancer
      patients with gemcitabine (500-1,000 mg/m(2) on days 1, 8, 15 every 4 weeks) as
      first-line, and 17 patients as second- or third-line treatment. RESULTS: The
      response rate of patients treated with gemcitabine as first-line and second- or
      third-line treatment was 5.3 and 28.5%, respectively. The median overall survival
      time in the first-, and second- or third-line treatment groups was 8.3 and 17.0
      months, and the 1-year survival rate was 44.0 and 50.9%, respectively. The
      present study also suggests the possibility that the prognosis of patients with
      high levels of C-reactive protein and total bilirubin, or a low level of albumin
      might be worse. CONCLUSIONS: Our results indicate that the treatment of
      inoperable biliary tract cancers with gemcitabine is feasible. There was no
      difference in the response rate and overall survival between biliary tract cancer
      patients in the first- and second- or third-line treatment groups. We also
      present the systematic review of literature of the recent treatment results of
      biliary tract cancers treated with gemcitabine.

PMID- 17179731
TI  - Predictive role of thymidylate synthase, dihydropyrimidine dehydrogenase and
      thymidine phosphorylase expression in colorectal cancer patients receiving
      adjuvant 5-fluorouracil.
AB  - OBJECTIVE: The combined assessment of thymidylate synthase (TS),
      dihydropyrimidine dehydrogenase (DPD) and thymidine phosphorylase (TP) gene
      expressions in metastatic colorectal cancer has been reported to be able to
      predict the efficacy of fluoropyrimidine-based chemotherapy. In order to evaluate
      the prognostic role in the adjuvant setting, we investigated the TS, DPD and TP
      expression in primary tumors of colorectal cancer patients treated with 5
      fluorouracil (5-FU). METHODS: TS, DPD and TP expression levels were determined by
      immunohistochemistry in paraffin-embedded primary tumor tissues from 62 patients
      with Dukes' stage B and C colorectal cancers who underwent surgery and received
      adjuvant systemic chemotherapy with 5-FU. The median follow-up was 90 months
      (range 17-127). RESULTS: Dukes' stage C cancer and high TS expression were
      independent markers of poor prognosis for disease-free survival (DFS; p = 0.0009
      and p = 0.007, respectively) and overall survival (OS; p = 0.0005 and p = 0.011,
      respectively). By multivariate analysis, patients with high DPD expression had
      significantly shorter DFS (p = 0.007) and OS (p = 0.005) compared to patients
      with low DPD expression. In the combined analysis of 2 markers, patients with low
      TS and low DPD had the best outcome in terms of DFS (p = 0.007) and OS (p =
      0.03). The analysis of all 3 proteins showed that the patients with low
      expression of all 3 markers had significantly longer DFS (p = 0.04) and OS (p =
      0.01) than patients with a high value of any one of the protein expressions.
      However, the joint analysis of 3 markers (group with TS-/DPD-/TP-) could not
      identify a subgroup of patients with a better prognosis compared to the analysis
      of 2 markers (group with TS-/DPD-). The analysis of Dukes' stage C cancer
      patients confirmed a significant benefit in terms of DFS and OS (p = 0.001 and p
      = 0.006, respectively) when all 3 markers had low expression. We also found a
      positive significant correlation between TS and TP protein expression (p =
      0.033). CONCLUSIONS: This retrospective investigation suggests that the combined
      assessment of TS and DPD may be useful to evaluate the prognosis of patients with
      Dukes' B and C colon carcinoma receiving 5-FU adjuvant chemotherapy. The role of
      TP as a predictor for 5-FU-based therapy needs further investigations.

PMID- 17179732
TI  - Gli-1 expression is associated with lymph node metastasis and tumor progression
      in esophageal squamous cell carcinoma.
AB  - OBJECTIVE: We investigated the expression and function of the hedgehog (Hh)
      pathway in human esophageal squamous cell carcinoma (ESCC). METHODS: The
      expression of Hh pathway molecules were detected in 34 human ESCC cell lines by
      RT-PCR. Subsequently, we investigated the effects of cyclopamine, a specific
      inhibitor of the Hh pathway, on cell proliferation, migration and invasion. Next,
      the effects of siRNA targeting Gli-1 were examined. Immunohistochemically, the
      expression of Gli-1 was studied in 104 ESCC specimens and compared with the
      clinicopathological characteristics of the patients. RESULTS: Gli-1 were
      expressed in 31 of 34 cell lines (91%), while Sonic hedgehog (SHh), Patched
      (Ptch), and Smoothened (Smo) expression was noted in all 34 cell lines.
      Cyclopamine significantly inhibited cell proliferation and migration in ESCC
      cells that expressed Gli-1. siRNA targeting Gli-1 inhibited cell growth in ESCC
      cells. Gli-1 was expressed in 52 of 104 cancer specimens (50%). Gli-1 expression
      was associated with tumor depth (p < 0.001), positive lymph node metastasis (p =
      0.004) and a poor prognosis (p = 0.0047). CONCLUSION: Our results raise the
      possibility that the inhibition of the Hh pathway could be a novel target for
      esophageal cancer therapy.

PMID- 17179733
TI  - Alternative medicine use in dialysis patients: potential for good and bad!
AB  - Although alternative medicines are widely used within the general population, the
      extent of their use within the dialysis population is unknown. It is possible
      that dialysis patients may be more likely to turn towards alternative therapies
      in view of the chronicity of their disease. In addition, this particular patient
      population could be at an increased risk of toxicity from these therapies due to
      an absence of renal excretion. A detailed assessment of complementary and
      alternative medicine use in our dialysis patients revealed that 18% of our
      patients had used or were using some form of alternative medicine therapy. An
      additional 63% of our patients, however, were willing to use a complementary or
      alternative medication. Our results suggest that hemodialysis patients are
      extremely receptive to the use of such therapies and are therefore exposed to all
      their potential benefit and harm.

PMID- 17179734
TI  - Prospective randomized study evaluating the efficacy of the spherical adsorptive
      carbon AST-120 in chronic kidney disease patients with moderate decrease in renal
      function.
AB  - AIMS: We studied whether adding the spherical adsorptive carbon AST-120 to
      conventional treatments is effective in inhibiting progression of chronic kidney
      disease (CKD) at the stage of moderate decrease in renal function. METHODS: 43
      CKD patients with moderately impaired renal function indicated by glomerular
      filtration rate (GFR) of 20-70 ml/min as measured by non-radiolabeled iothalamate
      clearance method were enrolled in the study. 26 patients showing a decrease of
      GFR by 5 ml/min during a 1-year observation period were randomized to receive
      ongoing treatments only (control group, 12 cases) or with AST-120 co-administered
      with ongoing treatment (AST-120 group, 14 cases). The intervention period was 1
      year and the change in GFR was the primary evaluation variable. RESULTS: The mean
      changes of GFR per month (DeltaGFR) in the intervention period were not
      significantly different between both groups. However, when comparing the DeltaGFR
      in the observation and intervention periods for each group, the rate of decline
      in GFR was significantly retarded (p < 0.001) in the AST-120 group while no
      significant difference was observed in the control group. CONCLUSION: These
      results suggest that co-administration of AST-120 with conventional treatments
      retards decline in renal function in CKD patients with moderate decrease in renal
      function.

PMID- 17179735
TI  - Biphasic pattern of exercise-induced proteinuria in sedentary and trained men.
AB  - BACKGROUND/AIMS: Exercise-induced proteinuria is a common consequence of physical
      activity, although its mechanism is not clear. Oxidant stress has been proposed
      as one of different factors involved in postexercise proteinuria in rats. In this
      study we investigated whether reactive oxygen radicals generated during exercise
      play a role in exercise-induced proteinuria in sedentary and trained men.
      METHODS: The validity of oxidant stress following stepwise maximal exercise on
      proteinuria was investigated in sedentary and trained subjects before and after
      antioxidant vitamin treatment (A, C, and E) for 2 months. While protein carbonyl
      content in serum and thiobarbituric acid reactive substances (TBARS) in
      erythrocytes and urine were used as oxidant stress markers, total protein,
      albumin, beta(2)-microglobulin in urine were assayed for proteinuria in five
      consecutive specimens after exercise. Urines were collected before exercise, then
      30 min, 2, 8 and 24 h postexercise. RESULTS: Increased urinary protein levels and
      mixed type proteinuria were determined after 30 min of exercise in sedentary and
      trained subjects. Proteinuria was normalized at 2 and 8 h specimens. However,
      glomerular type proteinuria was identified at 24 h specimen in both groups.
      Oxidant stress markers were significantly elevated in sedentary and trained
      subjects. Antioxidant treatment prevented the increase in oxidant stress markers,
      urinary protein levels and the occurrence of glomerular type proteinuria after
      exhaustive exercise at 24 h in both groups. CONCLUSIONS: These findings suggest
      that the exercise-induced oxidant stress may contribute to exercise-induced
      proteinuria in sedentary and trained men.

PMID- 17179736
TI  - In vitro paclitaxel and radiation effects on the cell types responsible for
      vascular stenosis: a preliminary analysis.
AB  - Hemodialysis vascular access dysfunction as a result of venous neointimal
      hyperplasia in dialysis access grafts and fistulae is currently a huge clinical
      problem. The aim of this study was to assess the effects of paclitaxel and
      radiation, both singly and in combination on the proliferation of cell types
      present within the lesion of venous neointimal hyperplasia (vascular smooth
      muscle cells, fibroblasts and endothelial cells within the neointimal
      microvessels). Vascular smooth muscle cells, fibroblasts and endothelial cells
      were plated onto 96-well plates and exposed to different concentrations and doses
      of paclitaxel and radiation, respectively (both individually and in combination).
      Growth inhibition was assessed with an MTT assay. Both paclitaxel and radiation
      resulted in significant growth inhibition of all three cell types. However, even
      small doses of paclitaxel appeared to attenuate the antiproliferative effect of
      radiation on these cell types. Further experiments to elucidate the mechanism
      behind these findings could result in a better understanding of combination
      antiproliferative therapies.

PMID- 17179737
TI  - Comparison of recurrence rates after anterior colporrhaphy for cystocele using
      three different surgical techniques.
AB  - AIMS: To compare the recurrence rates after anterior colporrhaphy for cystocele
      using three different surgical techniques: standard plicating, purse-string, and
      rolling anterior colporrhaphy. METHODS: A retrospective chart review of women
      undergoing anterior colporrhaphy for cystocele with or without concomitant
      operations between 1988 and 2000 was conducted. Women were assessed by vaginal
      examination pre- and postoperatively at 6 weeks and over 2 years. Grades of
      cystocele were assessed by Baden-Walker halfway grading system. chi(2) tests and
      ANOVAs were performed for categorical and continuous variables, respectively. Cox
      regressions were used to calculate recurrent rates. RESULTS: Among the studied
      363 women, 296, 33, and 34 underwent standard plicating, purse-string and rolling
      techniques, respectively. There was no significant difference in age, parity,
      menopausal status, or mean length of follow-up among the three groups. The purse
      string group revealed a significantly higher risk of recurrence than the standard
      plicating group (hazard ratio: 2.67; 95% CI: 1.05-6.08). The severity of
      cystocele was another key role of determining the prognosis for recurrences
      (grades 3 & 4 relative to grade 1, hazard ratio: 3.35; 95% CI: 1.34-8.38).
      CONCLUSION: Our study showed that standard plicating and rolling technique
      provided similar anatomic cure rates. However, the purse-string technique was
      less effective in restoring vaginal anatomy than standard plicating anterior
      colporrhaphy.

PMID- 17179739
TI  - Cyclic GMP synthesis by human retinal pigment epithelial cells is mainly mediated
      via the particulate guanylyl cyclase pathway.
AB  - BACKGROUND/AIMS: Cyclic 3',5'-guanosine monophosphate (cGMP), a central molecule
      in the phototransduction cascade, is also involved in a number of other
      physiological processes in the retina, like stimulating the absorption of
      subretinal fluid by activating the retinal pigment epithelium (RPE) cell pump.
      The aim of this study was to quantify cGMP synthesis by RPE cells and to
      investigate the role of two separate enzymatic pathways (soluble versus
      particulate guanylyl cyclase) in its production. METHODS: cGMP expression was
      evaluated by immunochemistry and radioimmunoassay following culture of the D407
      RPE cell line in the presence of a nonselective phosphodiesterase inhibitor
      (IBMX), in combination with the particulate guanylyl cyclase stimulator atrial
      natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium
      nitroprusside (SNP). RESULTS: Stimulation of the particulate guanylyl cyclase in
      RPE cells with ANP resulted in high intra- and extracellular cGMP levels.
      Stimulation of the soluble guanylyl cyclase by SNP resulted in a slight elevation
      of cGMP levels compared to controls. CONCLUSIONS: These results show that
      cultured human RPE cells are capable of producing cGMP and that most cGMP is
      generated following stimulation of the particulate guanylyl cyclase pathway.

PMID- 17179740
TI  - Protective effects of sodium daidzein sulfonate on trabecular bone in
      ovariectomized rats.
AB  - The ovariectomized (OVX) rat, as an established animal model of human
      osteoporosis, was adopted in the present experiment to study the protective
      effects of sodium daidzein sulfonate (SDS) on trabecular bone. Six-month-old
      Sprague-Dawley rats were sham-operated or ovariectomized. Five days later, the
      OVX rats were randomly assigned to one of three experimental groups and treated
      for 90 days with vehicle, 17beta-estradiol (E(2)) or SDS. Compared with OVX rats,
      SDS administration (15 mg/kg) prevented OVX-induced decrease in lumbar vertebral
      and femoral bone mineral density (BMD), and significantly increased bone
      mechanical strength parameters, including ultimate stress and elastic modulus. In
      the OVX group, the structure of trabecular plate in the femoral head was absorbed
      and became progressively thinner or was removed completely, accompanied by
      enlargement of marrow cavities and amalgamation of two or more marrow cavities.
      Administration of SDS and E(2 )prevented the change of trabecular bone
      microarchitecture induced by OVX, increasing the trabecular bone area and
      trabecular thickness, while decreasing the trabecular separation. These results
      indicate that SDS administration prevents OVX-induced decrease in BMD and bone
      mechanical strength, and has a moderate protective effect on the
      microarchitecture of trabecular bone in aged Sprague-Dawley rats.

PMID- 17179742
TI  - microRNA-mediated silencing inside P-bodies.
AB  - Cytoplasmic processing bodies, or P-bodies, contain a high concentration of
      enzymes and factors required for mRNA turnover and translational repression.
      Recent studies provide evidence that the mRNAs silenced by miRNAs are localized
      to P-bodies for storage or degradation, perhaps in adjacent subcompartments. mRNP
      remodeling, potentially induced by miRISC or RNA helicase activity, may cause the
      modification of the translation initiation complex at the 5' end of mRNA,
      following translational repression and localization to P-bodies. Further
      remodeling in P-bodies may facilitate access of the decapping complex to the cap
      structure, thus inducing mRNA degradation. However, with appropriate signals,
      stored mRNAs in P-bodies could be released and returned to the translational
      machinery through mechanisms requiring binding of regulatory proteins to the 3'
      UTR of mRNAs. Here a model is proposed to explain the repression and degradation
      stages of the mRNAs within PBs. This model includes preservation or disruption of
      a stable closed loop structure of the mRNAs, compartmentalization in PBs and mRNA
      escape triggered by additional binding proteins.

PMID- 17179741
TI  - Activation of serum response element by D2 dopamine receptor is governed by
      Gbetagamma-mediated MAPK and Rho pathways and regulated by RGS proteins.
AB  - In this study, we investigated the activation of the serum response element (SRE)
      by the D2 dopamine receptor (D2R) agonist quinpirole. Stimulation of CHO cells
      expressing the D2R by quinpirol evoked a dose-dependent SRE activation, which was
      completely blocked by overnight treatment of pertussis toxin or by co-expression
      of the beta-adrenergic receptor kinase C-terminus, implicating the involvement of
      Galpha(i )and Gbetagamma in the signal transduction. Furthermore, using MEK
      inhibitors and dominant negative mutants of RhoA, Rac1, and Cdc42, we showed that
      the Gbetagamma-mediated activation of the SRE in CHO cells utilizes both MAPK and
      Rho pathways. Expression of either regulator of G protein signaling 2 or 4 (RGS2
      or RGS4) proteins significantly attenuated the quinpirole-induced SRE activation.
      These results delineate the signaling pathways which couple D2 receptor to the
      transcriptional activation of SRE and demonstrate a modulatory role for RGS
      proteins in these processes.

PMID- 17179743
TI  - mRNA 3' of the A site bound codon is located close to protein S3 on the human 80S
      ribosome.
AB  - Ribosomal proteins neighboring the mRNA downstream of the codon bound at the
      decoding site of human 80S ribosomes were identified using three sets of mRNA
      analogues that contained a UUU triplet at the 5' terminus and a
      perfluorophenylazide cross-linker at guanosine, adenosine or uridine residues
      placed at various locations 3' of this triplet. The positions of modified mRNA
      nucleotides on the ribosome were governed by tRNA(Phe) cognate to the UUU triplet
      targeted to the P site. Upon mild UV-irradiation, the mRNA analogues cross-linked
      preferentially to the 40S subunit, to the proteins and to a lesser extent to the
      18S rRNA. Cross-linked nucleotides of 18S rRNA were identified previously. In the
      present study, it is shown that among the proteins the main target for cross
      linking with all the mRNA analogues tested was protein S3 (homologous to
      prokaryotic S3, S3p); minor cross-linking to protein S2 (S5p) was also detected.
      Both proteins cross-linked to mRNA analogues in the ternary complexes as well as
      in the binary complexes (without tRNA). In the ternary complexes protein S15
      (S19p) also cross-linked, the yield of the cross-link decreased significantly
      when the modified nucleotide moved from position +5 to position +12 with respect
      to the first nucleotide of the P site bound codon. In several ternary complexes
      minor cross-linking to protein S30 was likewise detected. The results of this
      study indicate that S3 is a key protein at the mRNA binding site neighboring mRNA
      downstream of the codon at the decoding site in the human ribosome.

PMID- 17179744
TI  - RNA interference: from biology to drugs and therapeutics.
AB  - RNA interference (RNAi) is a newly discovered and popular technology platform
      among researchers not only in the fields of RNA biology and molecular cell
      biology. It has created excitement in clinical sciences such as oncology,
      neurology, endocrinology, infectious diseases and drug discovery. There is an
      urgent need to educate and connect academic and industry researchers for the
      purpose of knowledge transfer. Thus, GeneExpression Systems of Waltham organized
      its Second International Conference in Waltham City (May 2-4, 2004, MA, USA) on
      the theme of 'RNA interference: From Biology to Drugs & Therapeutics.' About 200
      participants and 32 speakers attended this two and half-day event which was
      arranged in six scientific and three technology sessions and ended with a panel
      discussion. This report covers a few representative talks from academia, biotech
      and the drug industry.

PMID- 17179745
TI  - The complexity of mitochondrial tRNA import.
AB  - Import of nucleus-encoded, cytoplasmic tRNAs into mitochondria to compensate
      evolutionary loss of the corresponding mitochondrial genes has been documented in
      a large number of species. Although the phenomenon has been known for more than
      25 years, it was only recently that the mechanism of tRNA import started
      receiving the sustained attention of workers investigating yeast, protozoal and
      higher plant systems. The purpose of this review is to summarize recent
      developments that shed new light on the selectivity of the process, the identity
      of the import apparatus and the nature of the bioenergetic transactions leading
      to tRNA translocation, and to build a working model of the import complex
      suggested by these observations.

PMID- 17179746
TI  - RNomenclature.
AB  - RNAs that do not encode proteins, increasing evidence shows, are the rule rather
      than the exception. How do we call these RNAs? The term non-coding RNA should be
      rejected, we argue, since it constitutes a contradiction in terms: most if not
      all RNAs carry a code, even though that code may not specify an amino acid
      sequence. In naming these RNAs, we suggest to follow a natural distinction
      between two broad classes of RNAs. Class I RNAs are those that are transcribed
      but not translated, i.e., do not contain a translatable Open Reading Frame (ORF).
      Class II RNAs are transcribed and subsequently translated into amino acid
      sequences by the ribosomal translational apparatus. Class II RNAs comprise the
      familiar mRNAs, including peptide-coding RNAs. Class I RNAs, we suggest, are most
      fittingly called utRNAs (untranslated RNAs). The term npcRNAs (non
      peptide/protein coding) can be used synonymously.

PMID- 17179747
TI  - miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may
      downregulate the high affinity cationic amino acid transporter CAT-1.
AB  - These studies show that miR-122, a 22-nucleotide microRNA, is derived from a
      liver-specific noncoding polyadenylated RNA transcribed from the gene hcr. The
      exact sequence of miR-122 as well as the adjacent secondary structure within the
      hcr mRNA are conserved from mammalian species back to fish. Levels of miR-122 in
      the mouse liver increase to half maximal values around day 17 of embryogenesis,
      and reach near maximal levels of 50,000 copies per average cell before birth.
      Lewis et al. (2003) predicted the cationic amino acid transporter (CAT-1 or
      SLC7A1) as a miR-122 target. CAT-1 protein and its mRNA are expressed in all
      mammalian tissues but with lower levels in adult liver. Furthermore, during mouse
      liver development CAT-1 mRNA decreases in an almost inverse correlation with miR
      122. Eight potential miR-122 target sites were predicted within the human CAT-1
      mRNA, with six in the 3'-untranslated region. Using a reporter construct it was
      found that just three of the predicted sites, linked in a 400-nucleotide sequence
      from human CAT-1, acted with synergy and were sufficient to strongly inhibit
      protein synthesis and reduce mRNA levels. In summary, these studies followed the
      accumulation during development of miR-122 from its mRNA precursor, hcr, through
      to identification of what may be a specific mRNA target, CAT-1.

PMID- 17179748
TI  - Mutagenesis of Arg335 in bovine mitochondrial elongation factor Tu and the
      corresponding residue in the Escherichia coli factor affects interactions with
      mitochondrial aminoacyl-tRNAs.
AB  - During protein biosynthesis, elongation factor Tu (EF-Tu) delivers aminoacyl-tRNA
      (aa-tRNA) to the A-site of the ribosome. Mammalian mitochondrial EF-Tu (EF
      Tu(mt)) carries out this activity using aa-tRNAs that lack many of the invariant
      or semi-invariant residues that stabilize the 3-dimensional structures of
      canonical tRNAs. The primary sequence of EF-Tu is highly conserved. However,
      several residues involved in aa-tRNA binding are not conserved between the
      mitochondrial and bacterial factors. One such residue, located at position 287 in
      Escherichia coli EF-Tu, is adjacent to the 5' end of the aa-tRNA and is acidic in
      all prokaryotic factors but is basic in EF-Tu(mt). Site-directed mutagenesis of
      this residue (Glu287) in E. coli EF-Tu and complementary mutagenesis of the
      corresponding Arg335 in EF-Tu(mt) was performed to create E. coli EF-Tu E287R and
      EF-Tu(mt) R335E respectively. EF-Tu(mt) R335E has a reduced activity in ternary
      complex formation and A-site binding with mitochondrial Phe-tRNA.(Phe) In
      contrast, E. coli EF-Tu E287R is more active that the wild-type factor in forming
      ternary complexes with mitochondrial Phe-tRNA,(Phe) and the variant promotes the
      binding of mitochondrial aa-tRNA to the ribosome more effectively than does the
      wild-type factor. Both EF-Tu(mt) R335E and E. coli EF-Tu E287R have activities
      comparable to the corresponding wild-type factors in assays using E. coli Phe
      tRNA.(Phe) These data suggest that the residue at position 287 plays an important
      role in the binding and EF-Tu-mediated delivery of mitochondrial aa-tRNAs to the
      A-site of the ribosome.

PMID- 17179749
TI  - The translation elongation factor eEF1B plays a role in the oxidative stress
      response pathway.
AB  - The multi-subunit guanine nucleotide exchange factor eEF1B for Saccharomyces
      cerevisiae Translation Elongation Factor 1A (eEF1A) has catalytic (eEF1Balpha)
      and noncatalytic (eEF1Bgamma) subunits. Deletion of the two nonessential genes
      encoding eEF1Bgamma has no dramatic effects on total protein synthesis or
      translational fidelity. Instead, loss of each gene gives resistance to oxidative
      stress, and loss of both is additive. The level of stress resistance is similar
      to overexpression of the Yap1p stress transcription factor and is dependent on
      the presence of the YAP1gene. Cells lacking the catalytic eEF1Balpha subunit show
      even greater resistance to CdSO(4), with or without eEF1Bgamma present. Thus, the
      loss of guanine nucleotide exchange activity promotes the resistance. As
      nucleotide exchange is a critical regulator of most G-proteins, these results
      indicate a new mechanism in the growing list of examples of post-transcriptional
      responses to cellular stress.

PMID- 17179750
TI  - FMR1 RNA within the intranuclear inclusions of fragile X-associated tremor/ataxia
      syndrome (FXTAS).
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a recently identified
      neurodegenerative disorder affecting older adult males with premutation alleles
      of the fragile X mental retardation 1 (FMR1) gene. The principal clinical
      features of FXTAS include progressive intention tremor, gait ataxia,
      parkinsonism, and autonomic dysfunction. The disorder affects at least one-third
      of carrier males over 50 years of age and, with an estimated carrier frequency of
      approximately 1/800 males, is likely to be one of the most common heritable forms
      of tremor and ataxia among older adult males in the general population. Brains
      from all FXTAS cases examined to date (10/10) possess numerous ubiquitin-positive
      intranuclear inclusions in broad distribution throughout the cerebrum and
      brainstem. The absence of either the neurodegenerative disorder or inclusions
      among adults with fragile X syndrome (who lack the FMR1 protein), coupled with
      elevated FMR1 mRNA with expanded CGG repeats in premutation carriers, has led us
      to propose an RNA toxic gain-of-function model for FXTAS. Consistent with this
      model, we have now identified FMR1 mRNA within the intranuclear inclusions
      isolated from post-mortem (FXTAS) brain tissue.

PMID- 17179751
TI  - mRNAs associated with the Sam68 RNA binding protein.
AB  - The Src associated substrate in mitosis of 68kDa, Sam68, is an RNA-binding
      protein that belongs to the KH domain family of proteins. KH-type RNA binding
      proteins are known to mediate high affinity RNA binding and regulate RNA
      metabolism including pre-mRNA splicing, mRNA export and protein translation. The
      RNA binding specificity of Sam68 as well as its RNA targets are poorly
      understood. Herein we cross-linked mRNA associated with Sam68 and identified some
      of the mRNA associated with the Sam68 RNA binding protein complex. By using this
      strategy, we have identified 23 mRNAs that are associated with the
      immunoprecipitated endogenous Sam68 protein complex. Five of the identified mRNAs
      were validated by co-immunoprecipitation assay followed by reverse transcription
      PCR confirming that we had indeed identified mRNAs associated with the Sam68
      protein complex.

PMID- 17179752
TI  - The emergence of networks in human genome epidemiology: challenges and
      opportunities.

PMID- 17179753
TI  - "Big" science and the little guy.

PMID- 17179754
TI  - The evolution of epidemiologic research: from cottage industry to "big" science.

PMID- 17179755
TI  - How big is big enough for epidemiology?

PMID- 17179756
TI  - Are existing bacterial indicators adequate for determining recreational water
      illness in waters impacted by nonpoint pollution?

PMID- 17179757
TI  - Silica and lung cancer: when is enough evidence enough?

PMID- 17179758
TI  - Developmental arsenic neurotoxicity in retrospect.

PMID- 17179759
TI  - Detection of spatial clusters: application to cancer survival as a continuous
      outcome.
AB  - In this article, we develop the first detailed illustration of the use of a
      cluster detection method using a spatial scan statistic based on an exponential
      survival model. We use this approach to study the spatial patterns of survival of
      patients with stage III or stage IV colorectal cancer or with stage I/II, stage
      III, or stage IV lung cancer in the State of California and the County of Los
      Angeles (LA) diagnosed during 1988 through 2002. We present the location of the
      detected clusters of short survival or long survival and compute nonparametric
      estimates of survival inside and outside of those detected clusters confirming
      the survival pattern detected by the spatial scan statistic in both areas. In LA
      County, we investigate the possible relationship between the cluster locations
      and race, sex, and histology using nonparametric methods, and we compare
      socioeconomic factors such as education, employment, income, and health insurance
      inside and outside of the detected clusters. Finally, we evaluate the effect of
      related covariates on statistically significant long and short survival clusters
      detected in LA County using logistic regression models. This article illustrates
      a new way to understand survival patterns that may point to health disparities in
      terms of diagnosis and treatment patterns.

PMID- 17179760
TI  - Organochlorine exposures during pregnancy and infant size at birth.
AB  - BACKGROUND: Organochlorines, including polychlorinated biphenyls (PCBs) and
      pesticides, are environmentally persistent contaminants that concentrate in the
      food chain as well in human adipose tissue and readily cross the placenta.
      METHODS: To follow up on studies suggesting an association of organochlorine
      exposure with reduced birth size, we investigated the association of PCBs and
      organochlorine pesticides (including p,p'-dichlorodiphenyl dichloroethene [p,p'
      DDE], the major degradation product of p,p'-dichlorodiphenyl trichloroethane
      [p,p'-DDT], and hexachlorobenzene [HCB]), with birth weight, crown-heel length,
      and head circumference. We evaluated a cohort of 722 infants born between 1993
      and 1998 to mothers residing near a PCB-contaminated harbor and Superfund site in
      New Bedford, Massachusetts. RESULTS: Small negative associations were observed
      for PCBs and birth weight; associations were weaker for birth length and head
      circumference. There was evidence for effect modification by smoking during
      pregnancy on the association between PCBs and birth weight. No associations were
      found with p,p'-DDE or HCB for any measures of birth size. CONCLUSIONS: This
      study supports the growing literature that demonstrates at most a weak
      association between very low-level organochlorine exposure and birth size.

PMID- 17179761
TI  - Toward a global agenda for research in environmental epidemiology.
AB  - The global environment is in critical decline. Whether one's concern about
      environmental epidemiology stems from the perspectives of environmental health,
      climate change, ecological collapse, or growing inequity, clear problems exist.
      Natural capital resources are being depleted; disregard for the integrity of
      ecosystems is entrenched in current business practices. Indeed, despite
      increasing rhetoric to the contrary, the disregard displayed by those who hold
      power globally toward long-term sustainability and, thus, the health and well
      being of future generations, could be described as wanton. Six years ago, the
      Millennium Development Goals were announced by the United Nations as a rallying
      point for action to achieve a sustainable future, particularly by reducing the
      gap between the "have mores" and "have nots." The attainment of these Goals is
      now endangered, as is, apparently, the spirit of optimism and idealism that
      inspired them at the Millennium Summit. We call for a reinvigoration of both
      concern about-and action on-sustainability. In particular, we appeal to those
      engaged in the field of environmental epidemiology (and other specialties with
      whom they engage) to consider how they might help by incorporating sustainability
      issues (including global ecological integrity and global environmental justice)
      into their own research programs. This incorporation would make a vital
      contribution to protect both present and future generations and to reduce
      resource and health gaps between North and South. Simply put, we propose that
      sustainability becomes integral to advancing the science of environmental
      epidemiology and related environmental disciplines.

PMID- 17179762
TI  - Environmental sustainability: a target for environmental epidemiology?

PMID- 17179763
TI  - Joseph James Kinyoun: first director of the National Institutes of Health.

PMID- 17179764
TI  - Rotating shift work and risk of prostate cancer.

PMID- 17179765
TI  - Space-time clustering of cryptorchidism and hypospadias.

PMID- 17179766
TI  - Depressive symptoms increase risk of HIV disease progression and mortality among
      women in Tanzania.
AB  - The effect of depression on HIV disease progression was examined among 996 HIV
      positive Tanzanian women participating in a trial on micronutrients and pregnancy
      outcomes, vertical transmission, and disease progression. Depression and social
      support were measured 2 months after HIV screening and every 6 to 12 months
      thereafter. Depression measures from pregnancy and more than 12 months postpartum
      were included in this analysis. Participants' clinical condition and access to
      supportive individual or group counseling was assessed throughout the 6 to 8
      years of follow-up. Cox proportional hazard models were used to estimate the time
      varying effect of depression on progression to HIV clinical stage III/IV (World
      Health Organization) and all-cause mortality. Participation in group or
      individual counseling and baseline social support were also examined. More than
      half (57%) of the study sample had symptoms comparable with depression at least
      once during the follow-up period. Controlling for sociodemographic variables,
      psychosocial support, and clinical condition at enrollment, depression was
      associated with an increased risk of disease progression (HIV clinical stage
      III/IV [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.28 to 2.03] and
      mortality [HR = 2.65, 95% CI: 1.89 to 3.71]). Depression is common among HIV
      infected Tanzanian women and increases the risk of disease progression. Screening
      for depression and providing psychosocial interventions should be considered part
      of comprehensive HIV care.

PMID- 17179767
TI  - Incidence and risk factors for weight loss during dual HIV/hepatitis C virus
      therapy.
AB  - BACKGROUND: Clinical observations suggest that patients with HIV/hepatitis C
      virus (HCV) may lose body weight during dual therapy, but this has not been
      confirmed analytically. OBJECTIVES: To determine if the incidence and degree of
      weight loss among patients with HIV/HCV receiving highly active antiretroviral
      therapy (HAART) and pegylated (PEG)-interferon plus ribavirin were greater than
      in (1) HCV-monoinfected patients receiving PEG-interferon plus ribavirin and (2)
      HIV-monoinfected patients receiving HAART. Risk factors for weight loss among
      patients with HIV/HCV were also examined. METHODS: A retrospective cohort study
      was performed among HIV/HCV-coinfected, HCV-monoinfected, and HIV-monoinfected
      patients. Body weights were assessed up to 6 months before and up to 12 months
      after initiation of HCV therapy (HIV/HCV-coinfected and HCV-monoinfected
      subjects) and over 18 months on HAART (HIV-monoinfected subjects). The primary
      outcome was clinically significant weight loss (> or =5% of baseline weight).
      RESULTS: Of 192 subjects, 63 had HIV/HCV, 64 had HCV alone, and 65 had HIV alone.
      Clinically significant weight loss occurred in 48 (76%) subjects with HIV/HCV
      versus 25 (39%) subjects with HCV (P < 0.001) and 2 (3%) subjects with HIV (P <
      0.001), yielding adjusted hazard ratios (HRs) of 2.76 (95% confidence interval
      [CI]: 1.67 to 4.55) and 38.5 (95% CI: 8.5 to 174.7), respectively. Receipt of
      more than 2 nucleoside reverse transcriptase inhibitors increased the risk of
      clinically significant weight loss (adjusted HR = 8.17, 95% CI: 2.37 to 28.20).
      CONCLUSIONS: The incidence of weight loss is greater in dually treated patients
      with HIV/HCV than in treated HCV- or HIV-monoinfected patients. Prospective
      studies should evaluate additional risk factors for weight loss and changes in
      body composition to elucidate the mechanism for this weight loss.

PMID- 17179768
TI  - Time trends for HIV-1 antiretroviral resistance among antiretroviral-experienced
      and naive pregnant women in New York City during 1991 to early 2001.
AB  - Time trends in the prevalence of drug resistance to antiretroviral therapy (ART)
      in pregnant women have not been studied. Treatment and prophylactic efficacy
      could be compromised by drug-resistant HIV strains. We conducted a repeated cross
      sectional study of antiretroviral resistance mutations to nucleoside reverse
      transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase
      inhibitors (NNRTIs) and of major mutations to protease inhibitors (PIs) in virus
      isolates from 300 HIV-infected pregnant women in New York City from 1991 to early
      2001. The overall prevalence of mutations for NRTIs from 1991 to early 2001 was
      higher for ART-experienced (25.6% [95% confidence interval (CI): 19.1% to 32.1%])
      than ART-naive (8.6% [95% CI: 3.7% to 13.4%]) mothers (P < 0.002). For NNRTIs,
      the overall prevalence of mutations was somewhat higher among ART-experienced
      (5.8% [95% CI: 2.3% to 9.3%]) versus ART-naive (1.6% [95% CI: 0% to 3.7%]) women
      (P = 0.06), and increased over time for ART-naive women (0%-7.4%; P = 0.03) and
      ART-experienced women (0%-19.4%; P = 0.0002). The prevalence of PI-associated
      mutations was also higher overall among ART-experienced mothers (5.8% [95% CI:
      2.3% to 9.3%] vs. 1.6% [95% CI: 0% to 3.7%]; P = 0.06), with increases over time
      seen for ART-naive women (0%-7.4%; P = 0.03) and ART-experienced women (0%-16.1%;
      P = 0.0008). The increasing prevalence of drug resistance in pregnant women,
      including those who are drug-naive, underscores the necessity for resistance
      testing to guide treatment to achieve suppression of the mother's virus.

PMID- 17179769
TI  - A comparison of on-line and off-line sexual risk in men who have sex with men: an
      event-based on-line survey.
AB  - OBJECTIVE: To assess whether men who have sex with men (MSM) are more likely to
      report unprotected anal intercourse (UAI) with partners met on-line compared with
      those met off-line. METHODS: A total of 6122 individuals consented to participate
      in an anonymous behavioral survey on-line. This event-based analysis is limited
      to the 1683 men from the United States and Canada who had sex in the 3 months
      before the study and reported that their last sexual encounter included a new or
      casual male partner or partners. Prevalence and predictors of UAI were analyzed
      separately for the 386 men reporting more than 1 partner (multiple) and the 1297
      men reporting only 1 (single) partner in their last encounter. RESULTS: Of the
      1683 MSM recruited on-line, 51% met their partner(s) in their last sexual
      encounter on-line and 23% reported UAI. No difference in risk for UAI was found
      for partners met on-line versus off-line in the bivariate or multivariate
      analyses. In a multivariate analysis of men with multiple-partner encounters, UAI
      was significantly associated with being HIV-seropositive (adjusted odds ratio
      [OR] = 2.87; P = 0.02) in a model that included age; education; whether partners
      were met on-line or off-line; and use of crystal methamphetamine, sildenafil, or
      alcohol before sex. Using the same model, significant predictors of UAI in men
      reporting a single-partner encounter were use of crystal methamphetamine
      (adjusted OR = 5.67; P = 0.001) and no college degree (adjusted OR = 1.63; P =
      0.01). CONCLUSIONS: MSM recruited on-line who reported a new or casual sex
      partner(s) in the prior 3 months are at considerable risk of HIV or other
      sexually transmitted infections, but they are equally likely to report UAI
      whether sex partners were met on-line or off-line. The Internet may be an ideal
      venue for reaching high-risk MSM.

PMID- 17179770
TI  - Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV
      infected patients taking potent antiretroviral therapy: a randomized prospective
      study.
AB  - To assess the evolution of triglyceride (TG) levels in HIV-infected patients
      receiving stable potent antiretroviral therapy treated with N-3 polyunsaturated
      fatty acids (PUFAs), a prospective double-blind randomized design for a reliable
      assessment of TG evolution was performed. One hundred twenty-two patients with TG
      levels >2 g/L and < or =10 g/L after a 4-week diet (baseline TG: 4.5 +/- 1.9 g/L)
      were randomized for 8 weeks to N-3 PUFAs (2 capsules containing 1 g of fish oil 3
      times daily, n = 60), or placebo (1 g of paraffin oil capsules, n = 62). An 8
      week open-label phase of N-3 PUFAs followed. Evaluation criteria were TG percent
      change at week 8, percentage of responders (normalization or > or =20% TG
      decrease), and safety issues. Ten patients with baseline TG levels >10 g/L were
      not randomized and received N-3 PUFAs as open treatment. The difference (PUFA -
      placebo) in TG percent change at week 8 was -24.6% (range: -40.9% to -8.4%; P =
      0.0033), the median was -25.5% in the PUFA group versus 1% in the placebo group,
      and mean TG levels at week 8 were 3.4 +/- 1.8 g/L and 4.8 +/- 3.1 g/L,
      respectively. TG levels were normalized in 22.4% (PUFA) versus 6.5% (placebo) of
      patients (P = 0.013) with a > or =20% reduction in 58.6% (PUFA) versus 33.9%
      (placebo) of patients (P = 0.007). Under the open-label phase of N-3 PUFAs, the
      decrease in TG levels was sustained at week 16 for patients in the PUFA group
      (mean TG: 3.4 +/- 1.7 g/L), whereas a 21.2% decrease in TG levels occurred for
      patients in the placebo group (mean TG: 3.3 +/- 1.4 g/L). No significant
      differences were observed between groups in the occurrence of adverse events. The
      median TG change at week 8 was -43.6% (range: Q1-Q3; 95% CI: -66.5% to -4.6%) for
      patients with baseline TG levels >10 g/L. The difference in mean total
      cholesterol between groups (PUFA - placebo) at week 8 was -8.5% (P = 0.0117).
      This study demonstrated the efficacy of PUFAs to lower elevated TG levels in
      treated HIV-infected hypertriglyceridemic patients. N-3 PUFAs have a good safety
      profile.

PMID- 17179771
TI  - The role of vertical transmission and health care-related factors in HIV
      infection of children: a community study in rural Uganda.
AB  - OBJECTIVES: To determine the probable route of transmission of HIV to children
      aged 12 years or younger in a rural area of Uganda from 1999 through 2000 and to
      examine associations between HIV infection and health care-related variables.
      METHODS: The HIV infections status for 6991 children was determined from 1 round
      of an ongoing population surveillance system, and the reported numbers of
      injections in the past year and blood transfusions were determined for 5922 of
      these children based on a medical questionnaire. Data from the surveillance
      system and from an additional survey were used to assess the potential for
      vertical infection from a mother to her child. RESULTS: The HIV prevalence among
      children was 0.4%. Of 23 definite and 4 probable cases of HIV infection in
      children, vertical transmission was not possible for 1 case, not likely for
      another case, and possibly not vertical for another case. The population
      attributable fraction for vertical transmission was between 90% and 94%. Large
      numbers of injections in the past year and ever having a blood transfusion were
      only associated with HIV infection in children exposed to vertical transmission.
      CONCLUSIONS: Up to 10% of HIV infections in children in the study area were not
      attributable to vertical transmission, and thus were possibly attributable to
      iatrogenic transmission. Associations seen between health care-related variables
      and HIV were likely to be attributable to treatment for AIDS-related illness in
      children infected vertically.

PMID- 17179772
TI  - The effects of intravaginal clindamycin and metronidazole therapy on vaginal
      mobiluncus morphotypes in patients with bacterial vaginosis.
AB  - OBJECTIVE: The objective of this study was to compare the effects of treatments
      for bacterial vaginosis (BV) on vaginal Mobiluncus morphotypes. STUDY DESIGN:
      Analyses were performed on Mobiluncus scores from similarly conducted studies
      evaluating clindamycin vaginal single-dose cream (CVSDC) or metronidazole vaginal
      gel (MVG) in 55 patients with BV and with Mobiluncus morphotypes at baseline.
      RESULTS: Both treatment groups demonstrated significant reductions in Mobiluncus
      score. However, the Mobiluncus score at test-of-cure was lower in the CVSDC than
      in the MVG group (P=0.0471). More patients in the CVSDC group than in the MVG
      group achieved microbiologic (57.5% vs. 26.7%; P=0.04), clinical (57.5% vs.
      26.7%; P=0.04), and therapeutic cures of BV (45.0% vs. 20.0%; P=0.09).
      CONCLUSION: Clindamycin reduces vaginal Mobiluncus morphotypes to a greater
      extent than metronidazole in patients with BV; this correlates with a higher BV
      cure rate.

PMID- 17179773
TI  - Rising rates of syphilis in the era of syphilis elimination.
AB  - OBJECTIVE: The objective of this study was to assess the impact of syphilis
      control activities in King County, Washington. STUDY DESIGN: We calculated rates
      of early syphilis and trends in numbers of persons tested and diagnosed through
      screening and partner notification from 1998 to 2005. RESULTS: Early syphilis
      cases increased from 38 in 1998 to 188 in 2005 with 92% occurring among men who
      have sex with men (MSM). Our health department conducted public awareness
      campaigns, increased publicly financed syphilis screening among MSM by 179%, and
      intensified partner notification efforts. Despite these efforts, the prevalence
      of syphilis among screened populations was only 1.1%, and 71% syphilis cases were
      diagnosed after seeking care for symptoms. The proportion of cases diagnosed
      through screening and partner notification did not significantly change during
      the evaluation period. Early syphilis incidence among MSM more than doubled
      between 2003 and 2005. CONCLUSIONS: New, innovative approaches to syphilis
      control are needed.

PMID- 17179774
TI  - Discussing HIV serostatus with prospective sex partners: a potential HIV
      prevention strategy among high-risk men who have sex with men.
AB  - OBJECTIVE: To study factors associated with HIV serostatus discussions among men
      who have sex with men (MSM). DESIGN: The authors conducted a cross-sectional
      survey among MSM visiting an urban sexually transmitted infection (STI) clinic.
      METHODS: MSM were asked about sex partner recruitment, serostatus of partners,
      condom use, drugs use, and HIV serostatus discussions with sex partners. RESULTS:
      Among 1,400 MSM reporting occasional sex partners, serostatus discussion with
      100% of partners was reported by 509 (36.3%), with 50% to 99% of partners by 263
      (18.8%), and with <50% of partners by 628 (44.9%). Factors associated with
      serostatus discussion included lower number of sex partners, anal sex with an
      occasional partner, and sex partner recruitment through the Internet. Partner
      recruitment in bathhouses and having sex with both men and women were negatively
      associated. CONCLUSIONS: Discussion of HIV serostatus was common among MSM
      studied. Although this strategy has limitations, interventions should address HIV
      status discussions. Because the Internet may facilitate these discussions, web
      based interventions should be evaluated.

PMID- 17179775
TI  - Effectiveness of a risk-based visitor-prioritizing system at a sexually
      transmitted infection outpatient clinic.
AB  - OBJECTIVE: The objective of this study was to study the efficacy/effectiveness of
      a risk-based visitor-prioritizing system at a sexually transmitted infection
      (STI) clinic aimed to improve screening capacity by providing tailored service.
      STUDY DESIGN: In April 2004, a prioritizing system was implemented that
      classifies visitors as high or low risk depending on reported sexual behavior and
      previous STI events. The high- and low-risk groups are assigned to standard and
      short screening protocols, respectively. Both protocols include diagnostic
      testing for syphilis, urogenital gonorrhea, chlamydia, and optional for HIV. To
      assess the effectiveness of the system, differences in prevalence of STI
      diagnoses in the standard and short protocol were analyzed by chi test. RESULTS:
      In total, 14,391 visitors (64%) received standard screening and 8,056 visitors
      (36%) received short screening. The STI prevalence in both groups was 18.1% and
      7.6%, respectively (P <0.001); prevalence of HIV was 1.8% and 0.3%, respectively
      (P <0.001). The sensitivity of the prioritizing system was 74%. Specificity was
      substantially lower (42%). CONCLUSIONS: This prioritizing system is effective in
      differentiating between visitors at high and low risk for STI, contributing to
      provision of tailored STI service, increasing efficiency, and client access to
      STI service.

PMID- 17179777
TI  - Time trends in failure to return for HIV test results.
AB  - GOAL: The purpose of this study was to examine time trends of failure to return
      for HIV test results among a mobile van population in Los Angeles. STUDY DESIGN:
      This study examined administrative records from 9340 patients of the Mobile HIV
      Testing van between January 1997 and December 2004. RESULTS: Between 1997 and
      2004, a worsening trend was found in the percentage of clients who failed to
      return for HIV test results. Multivariate analyses showed that the adjusted odds
      of returning for test results significantly increased relative to 1997, the first
      year tested. The odds of returning for test results ranged from 1.56 (95% CI =
      1.21, 2.00) in 1998 to 2.46 (95% CI = 1.89, 3.19) in 2004. CONCLUSION: The
      proportion of MoHOP clients failing to return for test results was high and
      increased substantially between 1997 and 2004. Given the importance of
      identifying HIV-infected persons, understanding ways to improve return rates for
      test results is critical, especially for public health officials, clinicians, and
      researchers implementing and evaluating HIV prevention strategies.

PMID- 17179778
TI  - Primary frozen shoulder: global capsular stiffness versus localized contracture.
AB  - Stiffness in primary (idiopathic) frozen shoulders has been attributed to a
      global fibroplasia of the capsule despite the fact surgical release of the
      capsule at the rotator interval and of the coracohumeral ligament restores motion
      in almost all patients. Occurrence of vimentin, a cytocontractile protein known
      to be present in Dupuytren's contracture and in club-feet, has been reported in
      resection specimens of anterior capsular structures. We hypothesized vimentin
      would occur only in the anterior structures but fibroplasia would occur
      throughout the capsule. Tissues removed from four patients were stained with
      antibodies against vimentin, allowing us to confirm its presence in only in
      anterior capsular structures, supporting our first hypothesis contracture is due
      to a selective involvement of the anterior capsule. Staining the sections against
      types I and III collagen permitted the detection of both collagens in the
      anterior and the posterior capsular structures and thus confirmed our second
      hypothesis that fibroplasia involves the entire joint capsule. Therefore it
      seems, in patients with primary frozen shoulder, fibroplasia and contracture are
      two distinct processes.

PMID- 17179776
TI  - Demonstrating public health at work: a demonstration project of congenital
      syphilis prevention efforts in Bolivia.
AB  - OBJECTIVES: We introduced syphilis immunochromatic strip (ICS) tests into
      antenatal care (ANC) settings in Bolivia and evaluated feasibility, patient and
      provider acceptability, and introduction costs. We conducted complementary
      studies on related topics, strengthened quality of care, and aided the response
      to sensitive aspects of maternal/congenital syphilis control (e.g., partner
      notification). GOAL: The goal of this study was to discuss our experience working
      with Bolivian stakeholders to document potential public health benefits of
      syphilis ICS test introduction in ANC settings. STUDY DESIGN: We trained public
      health personnel and offered the Abbott Determine Rapid Syphilis TP test in 4
      urban maternity hospitals and 37 rural clinics. RESULTS: Using the ICS test,
      11,618 women were tested for syphilis; 5% had positive results and 93.2% received
      treatment. Women and health personnel found the test acceptable and introduction
      costs were not prohibitive. CONCLUSIONS: Based on these findings, by mid-2006,
      the Bolivian Ministry of Health will offer the ICS tests in rural ANC settings.

PMID- 17179779
TI  - The epidemiology of major joint contractures: a systematic review of the
      literature.
AB  - Current knowledge on the epidemiology of major joint contractures is limited. We
      systematically reviewed the literature to identify studies examining the
      epidemiology of joint contracture regardless of clinical condition. Epidemiologic
      measures of interest were prevalence, incidence, and prognostic risk factors. We
      used Medline to identify all epidemiologic studies of major joint contractures
      published from 1966 to March 2005. There was a high prevalence of major joint
      contractures. Most studies focused on one joint rather than including all
      relevant major contractures. However, most studies did provide a definition of a
      contracture or the measures used to assess contractures. Immobility is a highly
      prevalent disability in at-risk populations, and constitutes a tremendous burden
      to patients in nursing homes, hospitals, and the outpatient community. The lack
      of epidemiologic data is a major impediment to providing appropriate treatment.

PMID- 17179780
TI  - Quantitative analysis of local changes in patellar cartilage in spinal cord
      injured subjects.
AB  - Most studies investigating articular cartilage changes use global parameters and
      neglect the large topological variation in the response of cartilage to
      immobilization and remobilization. We hypothesized a registration-based semi
      automatic segmentation method would be highly reproducible to detect local
      changes in patellar articular cartilage thickness. We also hypothesized thinning
      of the cartilage is detectable in the smaller subregions of the patella in
      patients with a spinal cord injury (SCI) and the use of difference maps would
      allow us to detect early local thinning of the patellar cartilage. To determine
      the reproducibility, magnetic resonance images of the knee of seven healthy
      volunteers were acquired four times. Longitudinal changes were measured in the
      knees of seven patients with SCI as soon as possible, 6 months, and 12 months
      after the injury. Thickness maps and morphologic parameters for the cartilage of
      the patella and the four sub-regions were computed. The individual difference
      maps of 43% of the patients showed local areas of substantial thinning 6 and 12
      months after injury.

PMID- 17179781
TI  - Ceramic liner fracture after cementless alumina-on-alumina total hip
      arthroplasty.
AB  - Advances in technology have reduced the risk of fracture of ceramic total hip
      arthroplasty implants, but concerns remain about fracture of both components. We
      retrospectively reviewed 133 patients (157 hips) who had cementless alumina-on
      alumina total hip arthroplasties with a sandwich-type acetabular component. Six
      patients (seven hips) died and five patients (six hips) were interviewed by
      telephone (95% followup). The 122 patients (144 hips) examined had a minimum
      followup of 36 months (average, 45 months; range, 36-68 months). All acetabular
      cups and femoral stems were radiographically stable at the last followup. Five
      hips in five patients (3.5%) were revised because of ceramic liner fractures.
      Ceramic liner fractures occurred at a mean of 35 months (range, 24-48 months)
      postoperatively. Acetabular cups in the fracture group (n = 5) were more
      anteverted than those in the nonfracture group (n = 139). In three patients the
      fracture apparently occurred during squatting, resulting in hyperflexion and wide
      hip abduction. Early ceramic liner fracture was associated with impingement
      associated with excessive anteversion of the acetabular cup in Korean patients
      who habitually squat.

PMID- 17179782
TI  - Benefit of single-leaf resection for horizontal meniscus tear.
AB  - When treating a horizontal meniscus tear, the surgeon must decide whether to
      resect one or both leaves of the tear. We asked whether there is a biomechanical
      advantage to sparing one leaf when performing a partial meniscectomy for
      horizontal meniscus tear. We used pressure-sensitive film to measure the contact
      area, mean pressure, and peak pressure on the lateral tibial plateau of cadaveric
      sheep knees loaded to 2x body weight. For tears restricted to the posterior
      third, single-leaf resection decreased contact area by 40% compared with the
      intact case. Sparing one leaf was beneficial because resection of the second leaf
      reduced contact area an additional 15%. Similarly, mean pressure was increased
      24% for single-leaf resection and an additional 27% for double-leaf resection.
      Peak pressure showed no differences with single- and double-leaf resections. For
      tears that span the entire meniscus, single-leaf resection reduced contact area
      by 59%, increased mean pressure by 55%, and increased peak pressure by 19%.
      Double-leaf resection in this situation did not change these values
      substantially, suggesting sparing one leaf offers no benefit over resecting both
      leaves with extensive horizontal meniscus tears.

PMID- 17179783
TI  - Treatment of grade III acromioclavicular joint injuries: a systematic review.
AB  - Although nonoperative treatment is considered the standard of care for the
      treatment of Grade I and II acromioclavicular (AC) joint injuries, the treatment
      of Grade III injuries is controversial. There are as many methods of nonoperative
      treatment as there are for operative stabilization. Most of the literature
      represents Level IV evidence with very few Level II and III studies upon which to
      base decisions. A systematic review of the English-language literature was
      performed to determine if Grade III AC joint separations are best treated
      operatively or nonoperatively. Based on limited low-evidence, nonoperative
      treatment was deemed more appropriate than traditional nonoperative treatments
      because the results of the latter were not clearly better and were associated
      with higher complication rates, longer convalescence, and longer time away from
      work and sport.

PMID- 17179784
TI  - Surgical treatment of chronic patellar tendinosis: a systematic review.
AB  - There is no consensus in the literature on the best surgical procedure for
      patellar tendinosis when nonoperative treatment fails. With a systematic review,
      we asked whether surgical treatment of the inferior pole of the patella, closing
      of the paratenon, or immobilization affected the percentage of patients reporting
      good to excellent results (percent success). We completed a systematic review of
      surgical treatment for patellar tendinosis. A literature search of Medline,
      CINAHL, and Sport Discus revealed 30 articles on treatment of patellar
      tendinosis. Ten met our initial inclusion criteria. Most studies were
      retrospective and used varying techniques. Outcome measures were individual to
      the specific article, making it difficult to compare the results of the studies.
      Studies that described surgical treatment of the inferior pole of the patella had
      70.9% success compared to 91.7% for those that performed no patella bony work.
      Closure of the paratenon was reported in seven studies with 84.8% success
      compared to 91.5% for the other studies. Immobilization was used in four studies
      with 82.4% success compared to 94.9% success for four studies that did not
      immobilize postoperatively. Care must be taken when comparing these weighted
      averages since only two of the nine studies described exactly the same technique.
      Ideally, prospective controlled studies with validated assessment tools and
      activity scores are required to determine the best treatment for our patients.

PMID- 17179785
TI  - All-inside meniscus repair: a systematic review.
AB  - All-inside meniscus repairs are becoming more common with the invention of
      meniscal arrows, darts, screws, staples, and other suture devices. With the
      rising popularity of these new all-inside meniscal repair devices, it is
      necessary to assess the effectiveness of various all-inside surgical
      interventions used in the treatment of meniscal tears. We performed an evidence
      based review of the outcomes of all-inside meniscus repair devices. Seventy-seven
      percent of identified studies were case series; 10% were retrospective
      comparative studies; 6.5% were prospective comparative studies; and 6.5% were
      prospective randomized studies. The failure rates ranged from 0 to 43.5%. We
      found no substantial differences in the failure rates among various meniscus
      devices. We also found no substantial differences in failure rates with length of
      followup. Given the paucity of randomized controlled studies comparing different
      all-inside meniscal repairs, no definite conclusions can be made regarding the
      difference in clinical outcomes of various all-inside meniscal repair devices.

PMID- 17179787
TI  - Passive dorsiflexion flexibility after cast immobilization for ankle fracture.
AB  - Ankle fracture is frequently managed with cast immobilization, but immobilization
      may produce ankle contracture (loss of flexibility). We aimed to quantify
      recovery of ankle dorsiflexion flexibility in people treated with cast
      immobilization after ankle fracture, and to determine if initial orthopaedic
      management was associated with recovery. Ankle flexibility was measured in 150
      people with plantarflexion contracture who had been referred for outpatient
      physical therapy following cast immobilization for ankle fracture. We obtained
      measurements using an instrumented footplate within 5 days of cast removal and
      then 4 weeks and 3 months later. Data were compared with published normative
      data. Both stiffness and the torque corresponding to the peak dorsiflexion angle
      at baseline decreased during the 3 month recovery period, but recovery was still
      incomplete 3 months after cast removal. Surgical fixation was associated with
      higher stiffness, preload and torque values. Passive ankle flexibility does not
      return to normal values within 3 months of cast removal after ankle fracture.
      Recovery of normal ankle dorsiflexion flexibility typically takes longer than the
      initial period of immobilization.

PMID- 17179786
TI  - Indications for rotator cuff repair: a systematic review.
AB  - Despite the popularity of surgical repair of rotator cuff tears, literature
      regarding the indications for and timing of surgery are sparse. We performed a
      systematic review of the literature to investigate factors influencing the
      decision to surgically repair symptomatic, full-thickness rotator cuff tears.
      Specifically, how do demographic variables, duration of symptoms, timing of
      surgery, physical examination findings, and size of tear affect treatment outcome
      and indications for surgery? We reviewed the best available evidence, which
      offers some guidelines for surgical decision making. Variables suggest earlier
      surgical intervention may be needed in the setting of weakness and substantial
      functional disability. With regard to demographic variables, the evidence is
      unclear regarding their association with treatment outcome. However, older
      chronological age does not seem to portend a worse outcome. Pending worker's
      compensation claims does seem to negatively affect treatment results. Further
      research is required to define the indications for surgery for full thickness
      rotator cuff tears. However, the design and conduct of an ethical study to obtain
      Level I evidence on this issue will be a major challenge.

PMID- 17179788
TI  - Anatomy of the distal biceps brachii tendon and its clinical relevance.
AB  - Rupture of the distal biceps tendon is a relatively uncommon injury. Different
      methods have been described for its surgical repair. According to published
      reports, current surgical techniques result in decreased strength and endurance
      of upper extremity functions requiring supination and flexion. In our anatomic
      study of 74 cadaveric elbows, we observed that the distal biceps tendon spirals
      in a predictable manner and has a complex fiber arrangement. Successful surgical
      repair of a ruptured distal biceps tendon should be predicated on an
      understanding of the tendon anatomy, but current surgical techniques do not take
      into account the salient anatomic features of the distal biceps tendon. To our
      knowledge, there is no description in the surgical literature of the fiber
      arrangement of the distal biceps tendon. We provide a basis for developing an
      anatomically accurate protocol for repairing a distal biceps tendon rupture.

PMID- 17179789
TI  - Changing use of hormone therapy among minority women since the Women's Health
      Initiative.
AB  - OBJECTIVE: There has been a significant shift in the use of hormone therapy (HT)
      among nonminority women since the publication of results of the Women's Health
      Initiative (WHI). Little is known about how the WHI results affected minority
      populations. This survey measured patterns of HT use among inner city women after
      publication of the WHI results, identified factors involved in the decision to
      continue or discontinue HT, and characterized the symptom burden and the
      experience of women who attempted to discontinue HT. DESIGN: We conducted a cross
      sectional survey of 101 English- and Spanish-speaking women in an inner city
      general internal medicine clinic from August 2003 to April 2004. All women had
      been taking HT at the time of the publication of the WHI results. The survey
      included questions on patient-reported experience with HT, symptoms of menopause,
      and use of alternative treatments. RESULTS: Overall, 101 of 142 (71%) eligible
      women agreed to participate. The mean age of participants was 60 years; 43% were
      African American and 46% were Hispanic. The mean duration of HT use was 9.6
      years. Three quarters (74%) had heard about the WHI findings, and 87% had
      attempted to stop taking HT after their publication. The most common reason for
      attempting to stop HT was concern about an increased risk of cancer or a general
      increase in risk to health. Of those who stopped HT, the vast majority (85%)
      reported vasomotor symptoms, and 26% restarted HT, mostly to treat those
      symptoms. CONCLUSIONS: Nearly all minority women in this small sample attempted
      to stop HT use after the results of the WHI were published. Restarting HT for
      treatment of symptoms was common.

PMID- 17179790
TI  - Acupuncture for hot flashes.

PMID- 17179791
TI  - Nonvertebral "osteoporotic" fractures: a brain disease or bone disease?

PMID- 17179792
TI  - Evidence and opinion: closing the gap.

PMID- 17179793
TI  - Dual ectopic thyroid: case series and review of the literature.
AB  - Ectopic thyroid tissue is an uncommon congenital aberration. It is further
      unusual for ectopic thyroid to be present at 2 different sites simultaneously.
      Only 19 cases of dual ectopic thyroid have been reported in the English
      literature. Most of the patients were adolescents and presented with anterior
      neck swelling with or without altered metabolic status. Lingual/sublingual
      thyroid was the most common ectopic location. Subhyoid was the most common site
      of a second ectopic thyroid in these patients. The thyroid scan has been used
      successfully to diagnose ectopic thyroid tissue. We report 4 such cases in which
      ectopic thyroid tissue was simultaneously present at 2 different locations using
      thyroid scanning. The literature of already reported cases is reviewed in detail.

PMID- 17179794
TI  - Mismatch of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) and
      Tc-99m pertechnetate single photon emission computed tomography (SPECT) in a
      euthyroid multinodular goiter.
AB  - Imaging results of F-18 fluorodeoxyglucose (FDG) PET/CT scanning and Tc-99m
      pertechnetate scintigraphy of the thyroid gland are described and compared with
      pathology in a patient who was followed after left nephrectomy for renal cell
      carcinoma diagnosed 10 years earlier. On F-18 FDG PET/CT scanning, a multinodular
      struma with increased localized F-18 FDG uptake in 4 nodules was seen. Two
      nodules with increased glucose metabolism appeared normal on Tc-99m pertechnetate
      scintigraphy. Pathology indicated hyperplastic nodules. High focal F-18 FDG
      uptake was also seen in a lesion that corresponded with a "cold" nodule on Tc-99m
      pertechnetate scintigraphy, suggesting malignant disease. However, pathology
      revealed hyperplastic nodules with a background of aspecific lymphocytic
      thyroiditis. A fourth nodule with increased F-18 FDG uptake appeared mixed
      ("cold"/"hot") on Tc-99m pertechnetate scintigraphy. On pathology, a well
      differentiated follicular carcinoma was found. These findings, in a single
      patient, illustrate the wide spectrum of matched and mismatched F-18 FDG and Tc
      99m pertechnetate thyroid uptake along with their variable pathologic correlates.

PMID- 17179795
TI  - Preoperative dual-phase parathyroid imaging with tc-99m-sestamibi: accuracy and
      reproducibility of the pinhole collimator with and without oblique images.
AB  - BACKGROUND: Previously, we have found that the additional use of a pinhole
      collimator in parathyroid scintigraphy resulted in a decrease in the number of
      incorrect side localizations and an increase in reproducibility compared with
      that of using a parallel-hole collimator alone. PURPOSE: The aim was to
      investigate whether the addition of anterior oblique views to parathyroid
      scintigraphy (PS) with a pinhole collimator could further enhance the diagnostic
      ability and reproducibility. The level of preoperative parathyroid hormone (PTH)
      as a potential predictor of the usefulness of the supplementary views was also
      studied. METHOD AND MATERIAL: Forty-seven patients with primary
      hyperparathyroidism (HPT) underwent dual-phase PS using a combined protocol with
      parallel-hole and pinhole collimators. The pinhole collimator was used in the
      anterior as well as right and left anterior oblique positions. Thyroid
      pertechnetate scans were undertaken in the same positions. Two observers assessed
      the images independently. RESULTS: By adding oblique views, the gain in correct
      side localization occurred in all cases but one was seen in patients with rapid
      washout. The level of PTH could not predict these patients. The observer
      agreement on correct side localizations rose significantly from 81% to 94%.
      CONCLUSION: The addition of oblique views to the imaging protocol using the
      pinhole collimator for parathyroid and thyroid scintigraphy in primary HPT
      results in an increase in observer agreement and the number of correct side
      localizations in patients with rapid washout of MIBI. The preoperative level of
      PTH cannot, however, predict these patients.

PMID- 17179796
TI  - F-18 FDG PET/CT demonstration of an adrenal metastasis in a patient with
      anaplastic thyroid cancer.
AB  - An adrenal metastasis was identified on an F-18 FDG PET/CT scan in a patient with
      anaplastic thyroid cancer. There are very few reports of thyroid cancer, even
      anaplastic thyroid cancer, metastasizing to the adrenal.

PMID- 17179797
TI  - Hepatobiliary scintigraphy with SPECT in infancy.
AB  - Hepatobiliary scintigraphy (HBS) is an important investigation for the diagnosis
      of biliary atresia (BA) and its differentiation from causes of conjugated
      hyperbilirubinemia that do not require surgical intervention. Delayed imaging at
      24 hours and phenobarbitone augmentation for 5 days has been required to achieve
      high sensitivity and specificity with current techniques. This study explores
      whether adding single photon emission computed tomography (SPECT) performs as
      well as existing methods without requiring delayed 24-hour imaging and whether
      the phenobarbitone premedication is necessary in all cases. METHODS: A
      retrospective analysis of 105 HBS studies on 94 patients was performed. HBS
      included SPECT at 4 to 6 hours postinjection when no tracer was seen in the
      gastrointestinal tract in the first 60 minutes. This was done in 80 patients.
      RESULTS: Gastrointestinal activity was seen in 14 patients within 60 minutes. For
      4- to 6-hour studies, standard HBS and HBS with SPECT data showed a sensitivity
      of 100% for the diagnosis of BA. The specificity, accuracy, and positive
      likelihood ratios (PLR) were 67%, 75%, and 3 (confidence interval [CI]=2.03-4.16)
      for planar imaging at 4 to 6 hours and 90%, 93%, and 10 (CI=4.42-19) for 4- to 6
      hour planar and SPECT imaging. When the 11 patients who had phenobarbitone
      stimulation were included, the results improved to 97%, 98%, and 30 (CI=7.06-80).
      CONCLUSION: The addition of SPECT 4 to 6 hours postinjection of tracer
      significantly improves the diagnostic accuracy of hepatobiliary scintigraphy
      compared with planar imaging alone. This accuracy is as good as HBS performed
      after phenobarbitone stimulation. The combined technique of HBS with SPECT and
      phenobarbitone has the highest accuracy. Delayed imaging at 24 hours is usually
      not necessary.

PMID- 17179798
TI  - Different concentrations of I-123 MIBG and In-111 pentetreotide in the two main
      liver lobes in children: persisting regional functional differences after birth?
AB  - PURPOSE: At examinations in children with I-123 metaiodobenzylguanidine or with
      In-111 pentetreotide using SPECT, we have observed a different distribution of
      the radiopharmaceuticals between the left and right main liver lobes. This
      phenomenon was studied in retrospect from clinical examinations. PATIENTS AND
      METHODS: Seventeen children (mean age, 51 months; range, 11-150 months) with
      neuroblastoma or ganglioneuroma examined with both radiopharmaceuticals within 1
      week using SPECT were assessed. There was no history of liver disease and all
      liver lobes showed uniform activity distribution. Simultaneous radiologic
      examinations were all normal with regard to the liver. No child with a pathologic
      liver chemistry test was included. The activity ratios between the left and right
      main liver lobes were calculated from transverse tomographic sections. RESULTS:
      The mean left:right lobar activity ratio for I-123 metaiodobenzylguanidine was
      1.26+/-0.12 (null hypothesis=1.00; P<0.001) and for In-111 pentetreotide 0.88+/
      0.06 (null hypothesis=1.00; P<0.001). There was no age-dependent distribution of
      the tracers. The correlation between the tracer uptake of the different liver
      lobes was very weak. CONCLUSION: A functional difference between the 2 main liver
      lobes in utero is believed to reflect differences of the vascular supply. The
      current findings indicate a persisting functional heterogeneity of the liver
      after birth not caused by perfusion differences. A relatively higher uptake of I
      123 MIBG and a lower uptake of In-111 pentetreotide of the left liver lobe are
      normal findings.

PMID- 17179799
TI  - A second radiographic skeletal survey for child abuse triggered by bone
      scintigraphy found positive after the initial survey was called negative.

PMID- 17179800
TI  - Prostatic calcifications on Tc-99m-oxidronate bone SPECT.

PMID- 17179801
TI  - Tc-99m MDP bone scintigraphy and positron emission tomography/computed tomography
      (PET/CT) imaging in Erdheim-Chester disease.

PMID- 17179802
TI  - Combined effects of granulocyte colony stimulating factor and radiation.

PMID- 17179803
TI  - Paraesophageal hernia and aspiration of oral secretions demonstrated by nuclear
      salivagram.

PMID- 17179804
TI  - Sphenoid sinus bleeding during generalized seizure: a rare SISCOM (subtraction
      ictal SPECT coregistered with MRI) finding mimicking skull base tumor.

PMID- 17179805
TI  - Pleural effusion resulting from ventriculopleural shunt demonstrated on
      radionuclide shuntogram.

PMID- 17179806
TI  - Poor renal uptake of Tc-99m DMSA in a patient with oculocerebrorenal dystrophy
      (Lowe syndrome).

PMID- 17179807
TI  - Visualization of an insect bite on a bone scan.

PMID- 17179808
TI  - F-18 FDG PET imaging of disseminated sarcoidosis.

PMID- 17179809
TI  - Round pneumonia mimicking pulmonary malignancy on F-18 FDG PET/CT.

PMID- 17179811
TI  - Incidental PET/CT detection of thyroid and breast cancer during recurrence of
      colorectal carcinoma.

PMID- 17179810
TI  - Adenocarcinoma in an Indiana pouch on PET-CT.

PMID- 17179812
TI  - Abnormal iodine-131 uptake in a benign mucinous ovarian cystadenoma mimicking
      struma ovarii.

PMID- 17179813
TI  - Focal asymmetric longus colli uptake on FDG PET/CT.

PMID- 17179814
TI  - False-negative myocardial perfusion scintigraphy possibly as a result of
      administration of low-molecular-weight heparin.

PMID- 17179815
TI  - Incidental finding of thyroid uptake of tc-99m tetrofosmin on a myocardial
      perfusion scan.

PMID- 17179816
TI  - Isolated papillary muscle uptake on FDG PET/CT.

PMID- 17179818
TI  - Current readings in nuclear medicine.

PMID- 17179817
TI  - Primary cutaneous plasmacytoma presenting with multiple subcutaneous nodules by F
      18 FDG imaging.

PMID- 17179819
TI  - Heparin-induced inhibitory effects of a prothrombin complex concentrate on global
      tests of haemostasis.
AB  - Prothrombin complex concentrates (PCC) have been used as bypassing agents for the
      treatment of haemophilia A patients with inhibitor as well as for replacement
      therapy in congenital and acquired deficiencies of vitamin-K-dependent clotting
      factors. The efficacy of PCC is variable, however, especially during long-term
      and high-dose use, and all currently available products of this nature contain
      heparin. We have examined the haemostatic properties of PCC using reconstituted
      whole blood made by mixing coagulation-factor-deficient plasma and washed blood
      cells. In rotation thromboelastometry (ROTEM), the recommended therapeutic dose
      of Proplex ST corrected the abnormal patterns. At higher concentrations, however,
      the ROTEM patterns regressed. In addition, specific assays of coagulation factors
      appeared unreliable in the presence of 2.5 U/ml Proplex ST; the abnormalities
      were corrected when protamine sulfate was added. The findings suggest that the
      presence of heparin in PCC might have a greater effect on global haemostasis.
      Careful attention to the anticoagulant effect as well as thrombogenicity of PCC
      is required. Monitoring therapy using such as ROTEM analysis could be highly
      informative.

PMID- 17179820
TI  - Assessment of biochemical aspirin resistance at rest and immediately after
      exercise testing.
AB  - Some aspirin-treated patients experience thromboembolic events, a phenomenon
      termed 'aspirin resistance', which may be clinical or biochemical by definition.
      Physical exercise is known to enhance platelet secretion and aggregability. To
      evaluate the presence of biochemical aspirin resistance at rest and immediately
      after exercise in individuals with stable coronary artery disease or coronary
      artery disease risk factors. We prospectively enrolled 101 patients who had
      received 100 or 300 mg/day enteric-coated aspirin for at least 7 days.
      Biochemical aspirin resistance (defined as normal collagen-epinephrine closure
      time < 165 s) was studied using the standardized platelet function analyzer. Of
      the 101 patients, 63 were aspirin sensitive both at rest and immediately after
      exercise, 18 exhibited biochemical aspirin resistance both at rest and after
      exercise, and 20 were aspirin sensitive at rest but exhibited biochemical aspirin
      resistance immediately after exercise. The results of exercise testing were
      similar in all three groups (each P > 0.05). Our results indicate that in almost
      20% of the patients, aspirin did not seem to protect against exercise-induced
      platelet activation, despite the presence of aspirin sensitivity at rest. We did
      not, however, determine the extent to which the biochemical aspirin resistance
      noted in our study applied to clinical events.

PMID- 17179821
TI  - The alteration of plasminogen activator inhibitor-1 expression by linoleic acid
      and fenofibrate in HepG2 cells.
AB  - The present study investigated the influence of linoleic acid and fenofibrate on
      plasminogen activator inhibitor-1 (PAI-1) expression in HepG2 cells and the
      mechanism possibly involved. Using gene recombination techniques, chloromycetin
      acetyltransferase (CAT) reporter gene plasmids containing nuclear factor-kappaB
      response element deletion (del1-PAI-pCAT) or very-low-density lipoprotein/fatty
      acid response element deletion (del2-PAI-pCAT) in the PAI-1 promoter were
      constructed and transiently transfected into HepG2 cells, respectively. Linoleic
      acid and fenofibrate were added to induce the transfected cells. The PAI-1
      expression in mRNA and protein level was significantly induced by linoleic acid,
      but suppressed by fenofibrate. In the HepG2 cells transfected with PAI-pCAT
      plasmid, the PAI-1 transcription activity was significantly induced by linoleic
      acid, but suppressed by fenofibrate. Under transfection with del1-PAI-pCAT, both
      linoleic acid and fenofibrate increased the PAI-1 transcriptional activity;
      whereas in those cells transfected with del2-PAI-pCAT, fenofibrate significantly
      reduced PAI-1 transcriptional activity but no change was found with linoleic acid
      stimulation. Peroxisome proliferator-activated receptor alpha may be one of
      transcription factors playing a role in the upregulation of PAI-1 gene expression
      by linoleic acid in HepG2 cells. The inhibition of the nuclear factor-kappaB
      signaling pathway may be involved in the downregulation of PAI-1 gene expression
      by fenofibrate.

PMID- 17179822
TI  - The inflammation and coagulation cross-talk in patients with systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder with a high
      prevalence of cardiovascular disease due to accelerated atherosclerosis, as well
      as an increased risk of venous thromboembolism. Many of these clinical features
      have been attributed to the high prevalence of autoantibodies that are directed
      against phospholipid-bound antigens and that induce prothrombotic effects and
      disturb endothelial cell function. We conducted a case-control study in a cohort
      of female patients with SLE and in age-matched and sex-matched normal
      individuals. Patients had significantly higher levels of plasma inflammatory
      markers, but their overall coagulation status assessed by prothrombin fragment 1
      + 2 and D-dimer plasma levels was not different from controls. Resistance against
      activated protein C (APC), assessed by a thrombin generation-based as well as an
      activated partial thromboplastin time-based method, however, was increased in
      patients. This defect was neither due to factor V Leiden carriership or to the
      use of oral contraceptives. This acquired form of APC resistance was due to
      proinflammatory changes associated with lower plasma levels of free protein S. In
      conclusion, acquired APC resistance may be an important determinant of the risk
      of thrombosis in patients with SLE, probably due to an active cross-talk between
      inflammation and coagulation systems.

PMID- 17179823
TI  - Quantification of the effects of thrombin activatable fibrinolysis inhibitor and
      alpha2-antiplasmin on fibrinolysis in normal human plasma.
AB  - Two major proteins that inhibit fibrinolysis include thrombin activatable
      fibrinolysis inhibitor (TAFI) and alpha2-antiplasmin. Our goal was to quantify
      the contribution of TAFI and alpha2-antiplasmin to antifibrinolytic defenses with
      thrombelastography. Plasma activated with tissue factor/kaolin was subjected to
      fibrinolysis with tissue-type plasminogen activator (100 U/ml). Prior to
      activation, TAFI activity was inhibited with either potato carboxypeptidase
      inhibitor (25 microg/ml) or an anti-TAFI antibody, and alpha2-antiplasmin
      activity was inhibited with an anti-alpha2-antiplasmin antibody. Data were
      collected for 30 min, with the time of onset and rate of fibrinolysis determined.
      Compared with uninhibited samples, TAFI inhibition significantly (P < 0.05)
      decreased the time of onset of fibrinolysis by 70% and increased the rate of
      lysis by 70%. There was no difference between potato carboxypeptidase inhibitor
      and anti-TAFI antibody inhibition. Inhibition of alpha2-antiplasmin resulted in a
      significantly (P < 0.05) decreased time of onset (85%) and increased the rate of
      lysis (557%) compared with uninhibited samples. Inhibition of alpha2-antiplasmin
      activity resulted in a significantly (P < 0.05) greater fibrinolytic response
      than TAFI inhibition. In conclusion, utilization of standard inhibitors and
      thrombelastography permitted quantification of the effects of TAFI and alpha2
      antiplasmin on fibrinolysis in plasma. Future investigation of diseases involving
      hypofibrinolysis (e.g. left ventricular assist devices) could be conducted using
      this assay system.

PMID- 17179824
TI  - Epsilon-aminocaproic acid inhibition of fibrinolysis in vitro: should the
      'therapeutic' concentration be reconsidered?
AB  - The therapeutic concentration of epsilon-aminocaproic acid (EACA) has been 130
      microg/ml or greater for nearly 50 years. We tested the effects on clot
      growth/disintegration of EACA with a plasmatic model of hyperfibrinolysis in
      vitro. Human plasma was exposed to 1000 U/ml tissue-type plasminogen activator
      containing 0, 13, 65 or 130 microg/ml EACA, with clot growth/disintegration
      kinetics quantified via thrombelastography. Data were analyzed with one-way
      analysis of variance or Kruskal-Wallis analysis of variance as appropriate.
      Exposure of plasma to 1000 U/ml tissue-type plasminogen activator resulted in a
      brief-lived clot, lasting 2 min. EACA at all concentrations tested significantly
      increased the rate of clot growth compared with samples with 0 microg/ml EACA.
      Clot strength was significantly increased by EACA in a concentration-dependent
      fashion. Similarly, EACA significantly prolonged the time of onset of clot lysis
      and decreased the rate of lysis. Samples with 130 microg/ml EACA had no sign of
      lysis present for 30 min. Subtherapeutic to therapeutic concentrations of EACA
      significantly attenuated or abolished fibrinolysis in the presence of a
      concentration of tissue-type plasminogen activator more than 2000-fold that
      encountered systemically during cardiopulmonary bypass. Further clinical
      investigation is warranted to determine whether smaller concentrations of EACA
      could provide a reduction in bleeding with a concomitant decrease in thrombotic
      complications.

PMID- 17179825
TI  - Research for bleeding tendency in patients presenting with significant epistaxis.
AB  - To evaluate the association of inherited coagulopathies and acquired conditions
      (e.g. hypertension, aspirin use) with emergency department admission due to
      epistaxis. Patients admitted to the emergency department with epistaxis were
      included. A questionnaire for personal and family history of any bleeding
      disorder was used. Physical examination including ear, nose and throat
      examination was performed. Platelet counts, International Normalized Ratio,
      activated partial thromboplastin time, factors VIII, IX and XI, von Willebrand
      factor and ristocetin cofactor activity levels were determined. Nineteen patients
      were included in the study. Personal history of mucocutaneous bleeding was
      present in four cases and family history in two cases. Only one case (5%) had a
      decreased von Willebrand factor level (45%), and also had a personal and family
      history of bleeding tendency. Ten patients (53%) had a history of aspirin use.
      Thirteen (68%) patients had hypertensive values on admission. Aspirin use and
      hypertension were the leading causes of emergency service admission in adults due
      to epistaxis in this study, although the number of the patients was relatively
      low. Regarding the low prevalence of inherited coagulopathies, detailed
      coagulation tests should be reserved for adult patients with positive personal
      and/or family history of bleeding.

PMID- 17179826
TI  - Thrombelastographic measures of clot propagation: a comparison of alpha with the
      maximum rate of thrombus generation.
AB  - The alpha angle alpha (degrees) is a thrombelastographic measure of clot
      propagation. A parametric measurement of clot propagation [maximum rate of
      thrombus generation (MRTG), dynes/cm2 per s], however, has recently been
      utilized. Thus, the relationship of changes in alpha with changes in MRTG were
      determined. alpha and MRTG values obtained from 859 thrombelastograms was
      collected from nine studies. Data were analyzed and the relationship between
      alpha and MRTG defined with commercially available software. Additional
      comparisons were made retrospectively from whole-blood and plasma data obtained
      from 33 normal individuals. Data from the nine studies demonstrated that MRTG
      increased in an exponential fashion compared with increases in alpha (R2 = 0.88,
      P < 0.001). Whole-blood alpha values were in the range 66.7-74.7 whereas MRTG
      values were 5.5-10.8, and plasma alpha values were 65.1-77.9 with corresponding
      MRTG values of 3.5-12.0. Assessment of clot propagation utilizing MRTG provides a
      more parametric evaluation than the determination of alpha. While normal alpha
      values may vary by only 12-20%, MRTG values vary by approximately 200-300%. The
      MRTG should be progressively utilized to a greater extent in both laboratory and
      clinical settings to parametrically quantify clot growth kinetics with
      thrombelastography.

PMID- 17179828
TI  - In-vitro efficacy of different platelet glycoprotein IIb/IIIa antagonists and
      thrombolytics on platelet/fibrin-mediated clot dynamics in human whole blood
      using thrombelastography.
AB  - Suppressing platelet activation improves efficacy of thrombolytic therapy for
      stroke and acute myocardial infarction. Combination treatment with recombinant
      tissue plasminogen activator (r-tPA) and glycoprotein IIb/IIIa (GPIIb/IIIa)
      inhibitor that binds with high affinity to platelets may therefore improve the
      efficacy of thrombolytic therapy. The effect of platelet GPIIb/IIIa antagonists
      and/or r-tPA on the dynamics of platelet/fibrin clot formation, strength, and
      lysis was determined using thrombelastography in human blood under thrombin or
      tissue factor stimulation. The study utilized platelet GPIIb/IIIa antagonists
      with high affinity and slow off-rate (Class I) from resting and activated
      platelets in comparison with Class II antagonists (lower affinity and fast off
      rate from platelet GPIIb/IIIa receptors). The combination of the active form of
      roxifiban (XV459; Class I) or the active form of orbofiban (Class II) with a
      subeffective concentration of r-tPA resulted in a synergistic effect in clot
      lysis with roxifiban active form XV459 but not with that of orbofiban at
      therapeutically achievable concentrations that inhibit human platelet
      aggregation. These data indicate differential enhanced thrombolysis of low levels
      of r-tPA with high-affinity Class I but not with low-affinity Class II GPIIb/IIIa
      antagonists in the absence of anticoagulants.

PMID- 17179827
TI  - Hydroxyethyl starch enhances argatroban-mediated decreases in clot propagation
      and strength by diminishing thrombin-fibrinogen interactions.
AB  - Direct thrombin inhibitors (DTIs) have been administered for anticoagulation
      during cardiopulmonary bypass for patients with heparin-induced thrombocytopenia.
      While DTIs prolonged clot initiation and decreased clot propagation, clot
      strength did not change. Hydroxyethyl starches (HES), however, significantly
      decreased clot propagation and strength. We hypothesized that DTI with HES could
      significantly decrease hemostasis more than DTI alone. Plasma was exposed to 0 or
      5 microg/ml argatroban with 0 or 30% dilution with 0.9% NaCl, 10% pentastarch or
      6% Voluven. Additional argatroban-exposed samples diluted with HES had addition
      of alpha-thrombin (0.25 U/ml) and fibrinogen (150 mg/ml). Clot kinetics were
      determined via thrombelastography. While dilution with 0.9% NaCl significantly (P
      < 0.05) decreased the clot strength by 17% compared with samples only exposed to
      argatroban, dilution with pentastarch and Voluven significantly (P < 0.05)
      markedly decreased clot strength (53 and 78%, respectively). Voluven dilution
      significantly increased the time to clot initiation and decreased the velocity of
      clot propagation compared with samples only exposed to argatroban. Addition of
      alpha-thrombin/fibrinogen restored clot strength. DTI/HES administration
      diminished hemostasis to a greater extent than DTI exposure alone. Further
      investigation is warranted to determine whether this therapeutic approach can
      improve the safety of anticoagulation during cardiopulmonary bypass in patients
      with heparin-induced thrombocytopenia.

PMID- 17179829
TI  - Thrombin generation by hemolysis.
AB  - Hemolysis is the fragmentation of erythrocytes into microparticles (Hb-MP).
      Clinical hemolysis can result in a severe procoagulant state. The influence of Hb
      MP on thrombin generation was quantified. Unfrozen citrated normal plasma (five
      donors) was supplemented with 0 or 1 g/l Hb-MP obtained through erythrocyte
      destruction by hypotonic lysis, freezing/thawing, or blood oxidation with 1 or 2
      mmol/l chloramine-T. Pooled normal plasma was supplemented with 0-10 g/l Hb-MP
      and with 0-1 IU/ml low-molecular-weight heparin (dalteparin). Samples (50 microl)
      were tested in the recalcified coagulation activity assay. At 10 min coagulation
      reaction time the hypotonic lysis of erythrocytes appears to be the most
      procoagulant condition, followed by twice freezing/thawing, three times
      freezing/thawing, and once freezing/thawing. Oxidation of whole blood with 1 or 2
      mmol/l chloramine-T decreases thrombin generation by about 20 or 50%,
      respectively. The thrombin generation in 1 mmol/l chloramine-T or 2 mmol/l
      oxidized plasma decreases by about 70 or 85%, respectively. The 50% inhibitory
      concentrations of low-molecular-weight heparin against recalcified thrombin
      generation are 0.01, 0.025, or 0.035 IU/ml for plasma supplemented with 0, 0.1,
      or 1 g/l Hb-MP, respectively. The recalcified coagulation activity assay allows
      one to quantify thrombin generation in critical hemolytic samples. It is
      suggested to find the appropriate pharmacologic dose of low-molecular-weight
      heparin.

PMID- 17179830
TI  - Influence of coagulation factors on intrinsic thrombin generation.
AB  - The intrinsic coagulation activity assay (INCA) is a new thrombin-generation test
      that imitates the intrinsic pathway of blood coagulation. The aim of the present
      study was to investigate the influence of the main coagulation factors on the
      INCA. The INCA was performed with citrated plasma samples supplemented with
      different amounts of fibrinogen. The INCA and activated partial thromboplastin
      time determination were performed with factor-depleted plasmas and with mixtures
      of depleted plasmas with normal plasma. Supplemented purified fibrinogen resulted
      in a decrease of intrinsic thrombin generation (50% inhibitory concentration =
      0.8 g/l). The INCA depends on the intrinsic factors (factors VIII, IX, XI and
      XII) and on the factors of the common pathway (factors II, V and X): for normal
      thrombin generation, at least about 50% of normal factor II is necessary. For the
      majority of factors, the sensitivity of the INCA appears to be approximately one
      order of magnitude better than that of the activated partial thromboplastin time.
      The INCA allows one to diagnose defects in the intrinsic coagulation system and
      might be a useful test to support development and characterization of new drugs
      targeted at the intrinsic generation of thrombin.

PMID- 17179831
TI  - A case of afibrinogenemia associated with A-alpha chain gene compound
      heterozygosity (HUMFIBRA c.[4110delA]+[3200+1G>T]).
AB  - The clinical features and molecular biology data of a case of afibrinogenemia are
      reported. The propositus is a 14-year-old girl who suffered several bleeding
      manifestations that were successfully treated with fibrinogen infusion. The
      afibrinogenemia results from compound heterozygosity for two mutations on the
      Aalpha chain gene (c.[4110delA]+[3200+1G>T]). The first mutation is a novel
      frameshift mutation inherited from her father. The second is a previously
      described Aalpha chain gene splice junction mutation inherited from her mother.
      Neither of the parents fulfills the criteria for hypofibrinogenemia.

PMID- 17179832
TI  - Negative pressure dressing for promoting wound healing of purpura fulminans in a
      newborn with homozygous protein C deficiency.
AB  - A negative pressure dressing to promote wound healing of purpura fulminans in a
      girl aged 35 days with homozygous protein C deficiency is reported. Two wounds of
      11 x 11 cm2 at the abdominal wall and 14 x 14 cm2 at the left trunk were covered
      with sterile sponges embedded with a multiple-hole drain tube and transparent
      plastic film. The exposed end of the drain was then connected to the wall suction
      apparatus to create negative pressure at -120 mmHg. The dressing was changed
      every 2 days. Within 4-6 weeks, the wounds were completely healed and skin
      grafting was not required.

PMID- 17179833
TI  - Molecular characterization of an Italian patient with plasminogen deficiency and
      ligneous conjunctivitis.
AB  - Plasminogen deficiency is a rare disease characterized by ligneous conjunctivitis
      and infections. We observed a 3-year-old Italian boy presenting ligneous
      conjunctivitis and low plasma levels of plasminogen. Twenty-three different
      mutations on the PLG gene have been reported to date, but mutation analysis had
      been troublesome for the presence of highly homologous genes. The aim of the
      study was to identify the underlying mutation avoiding coamplification of
      unwanted genetic materials using a long polymerase chain reaction strategy,
      instead of the previously reported subcloning methods. By this simple strategy
      the complete sequence analysis of PLG gene was performed, and a previously
      reported missense homozygous mutation (K19E) was identified.

PMID- 17179834
TI  - Modifications of protein Z and interleukin-6 during the acute phase of coronary
      artery disease.

PMID- 17179835
TI  - Preanalytical variables in coagulation testing.

PMID- 17179836
TI  - An interdisciplinary expert consensus statement on assessment of pain in older
      persons.
AB  - This paper represents an expert-based consensus statement on pain assessment
      among older adults. It is intended to provide recommendations that will be useful
      for both researchers and clinicians. Contributors were identified based on
      literature prominence and with the aim of achieving a broad representation of
      disciplines. Recommendations are provided regarding the physical examination and
      the assessment of pain using self-report and observational methods (suitable for
      seniors with dementia). In addition, recommendations are provided regarding the
      assessment of the physical and emotional functioning of older adults experiencing
      pain. The literature underlying the consensus recommendations is reviewed.
      Multiple revisions led to final reviews of 2 complete drafts before consensus was
      reached.

PMID- 17179837
TI  - Cardiopulmonary resuscitation: how far have we come?
AB  - In the 43 years since it was first described, cardiopulmonary resuscitation (CPR)
      has grown from an obscure medical theory to a basic first aid skill taught to
      adults and is now the near-universal technique used in CPR instruction. This
      article provides insight into the history of CPR. We explore the phenomenon of
      sudden cardiac arrest, the historical roots of CPR, current practice data and
      recommendations, and the society's role in the development of this life-saving
      technique. We conclude with a review of CPR's economic impact on the healthcare
      system and the ethical and policy issues surrounding CPR.

PMID- 17179840
TI  - Healing Touch: a low-tech intervention in high-tech settings.
AB  - Healing Touch is a complementary therapy that can be used as a nursing
      intervention for patients in critical care settings. Use of healing touch may
      facilitate positive patient outcomes. However, further research is needed to
      adequately evaluate the effectiveness of healing touch in the critical care
      setting. The use of Healing Touch in critically ill patients is explored in this
      article.

PMID- 17179842
TI  - Innovative solutions: leading the way: an innovative approach to support nurses
      on general care units with an early nursing intervention team.
AB  - In an effort to improve patient outcomes, there has been a global initiative to
      prevent avoidable adverse events. The rapid response team or medical emergency
      team concept has been in existence for the past several years and there has been
      a significant improvement in patient outcomes. This article will describe one
      institution's success in taking this concept even further by rounding on general
      care units before patient problems are evident. The focus of this discussion will
      be on the remarkably positive nursing staff outcomes that have been achieved as a
      result of a program called the Early Nursing Intervention Team, a totally nurse
      led program.

PMID- 17179843
TI  - A grief team within a healthcare system.
AB  - Grief is an emotion experienced by many nurses upon the death of a patient, and,
      far too often, the nurse may not know how to deal effectively with his or her
      grief. This article describes the development of a grief team within a hospital
      setting to assist nurses in coping with grief.

PMID- 17179844
TI  - Barriers to achieving patient-centered care in Ireland.
AB  - In today's healthcare environment, patient care has become fragmented and
      impersonalized even though we desire to give person-centered care. Many factors
      affect the way we must deliver nursing care. This article discusses patient care
      in Ireland in the contemporary intensive care setting that has become more task
      oriented and less patient-centered.

PMID- 17179851
TI  - The power of silence.

PMID- 17179854
TI  - Event-related theta activity reflects memory processes in pronoun resolution.
AB  - A recent eye-tracking study reported a reverse effect of a noun's lexical
      frequency in the context of the resolution of coreferring pronouns. Investigating
      the neurophysiological basis of this effect, the present electroencephalographic
      study found differential patterns in theta activation when participants read
      pronouns referring to nouns of different frequency classes. Evoked theta power
      after pronoun onset increased with the frequency of the critical noun. This
      finding suggests differential load on memory resources depending on the nouns'
      frequency. Elevated attention promoting memory encoding for low-frequency words
      is assumed to facilitate the resolution of pronouns. Location of sources of
      differential theta activity in the parahippocampal region is accounted for by its
      role in an association network that mediates memory processes.

PMID- 17179855
TI  - Spatial integration of visual motion with separate speed and direction
      information.
AB  - We present evidence to support the possibility that motion information is divided
      into two scalars: direction and speed, to integrate local motions over a wide
      spatial range. With various motion stimuli composed of numerous red and green
      dots, observers perceived that peripheral dots moved similar to central dots on
      the basis of the same direction or speed, even when speed or direction was
      different. The results indicate that the direction and speed of local motion can
      be processed separately and that the distributions are analyzed independently to
      integrate the local motions. This process, based on two motion scalars, may be
      useful for the perception of complex motions that would be difficult to perceive
      with a process based on motion vectors.

PMID- 17179856
TI  - Conserved role of brain-derived neurotrophic factor in Val66Met: target-selective
      reinforcement of GABAergic synapses.
AB  - Brain-derived neurotrophic factor has been implicated in higher cognitive
      functions, and several neurological and psychiatric disorders. Recently, a
      variant brain-derived neurotrophic factor (BDNFMet), having a substitution
      referred to as Val66Met, was reported as a product of a bdnf allele with a common
      single nucleotide polymorphism. It has been reported that BDNFMet is impaired in
      its potential for activity-dependent release. We sparsely transfected cultured
      hippocampal neurons with BDNFMet or wild-type BDNFVal cDNAs and examined the
      amount of GABA-synthetic enzyme glutamic acid decarboxylase 65 (GAD65) in the
      adjacent region, probably in the GABAergic synapses. BDNFMet transfection
      increased the GAD65 level to the same extent as transfection with BDNFVal. Our
      findings suggest that the activity-independent secretion of brain-derived
      neurotrophic factor may be sufficient to induce inhibitory regulation.

PMID- 17179857
TI  - Neural correlates of absolute pitch differ between blind and sighted musicians.
AB  - Several reports have indicated a higher incidence of absolute pitch in blind than
      in sighted musicians. Employing a pitch memory task, we examined whether a blind
      absolute pitch musician would rely on different neural correlates than a group of
      sighted absolute pitch musicians. The blind musician showed significantly more
      activation of bihemispheric visual association areas, lingual gyrus, parietal and
      frontal areas than the sighted musicians. Sighted musicians showed more
      activation of the right primary auditory cortex and the cerebellum when compared
      with the blind musician. These differences in the activation pattern suggest the
      use of a different neural network including visual association areas while
      performing pitch categorization and identification in this blind musician in
      comparison with sighted musicians.

PMID- 17179859
TI  - Quantitative analyses of leukemia inhibitory factor in the cerebrospinal fluid in
      mouse embryos.
AB  - Leukemia inhibitory factor contributes to the self-renewal of neural stem cells
      in the forebrain. Although the existence of endogenous leukemia inhibitory factor
      in the brain parenchyma has been controversial, the cerebrospinal fluid is known
      to be another source of leukemia inhibitory factor. No reports of the measurement
      of leukemia inhibitory factor concentrations in the cerebrospinal fluid, however,
      exist. In the present study, we determined the leukemia inhibitory factor
      concentration in cerebrospinal fluid, amniotic fluid, and sera of embryos and
      dams in mice by enzyme-linked immunosorbent assay. The leukemia inhibitory factor
      concentrations were found to be constitutively high in the cerebrospinal fluid
      from embryonic day 11 to embryonic day 17, with a peak on embryonic day 13 and
      embryonic day 14. These findings correspond to the timing of cortical neuron
      production in mouse cerebrum.

PMID- 17179858
TI  - A novel P755L mutation in LRRK2 gene associated with Parkinson's disease.
AB  - Parkinson's disease is a common neurodegenerative disorder. The identification of
      leucine-rich repeat kinase 2 (LRRK2) gene mutations as a cause of Parkinson's
      disease has greatly expanded our knowledge of the genetic and molecular
      pathogenesis of this disorder. By denaturing high-performance liquid
      chromatography and gene sequencing in patients and controls, we identified a
      novel frequent heterozygous 2264C-->T substitution, which causes a proline-to
      leucine mutation (P755L) in LRRK2 gene. In our sample of 598 patients of Chinese
      Han ancestry, 12 cases carried the same LRRK2 mutation. Our results indicated
      that this single mutation was implicated in 2% of sporadic patients. We suggest
      that testing for this mutation will be important in the management and genetic
      counseling of patients with Parkinson's disease.

PMID- 17179860
TI  - Expression of the exon 3 skipping form of GLAST, GLAST1a, in brain and retina.
AB  - GLAST is a glial glutamate transporter; mRNA for a splice variant, GLAST1a, which
      lacks exon 3, has previously been identified. To detect GLAST1a protein, we
      generated antibodies against a peptide sequence encompassing the splice site. We
      demonstrate by Western blotting and immunocytochemistry the expression of GLAST1a
      in brains and retinae. Robust immunolabelling was present in the cerebellar
      Bergmann glia, and weaker labelling was evident in the retinal Muller cells.
      GLAST1a is differentially targeted to some cellular compartments such as the end
      feet of the Muller cells. As GLAST1a protein may interfere with the transport of
      glutamate by normally spliced GLAST, differentially targeted expression of
      GLAST1a may represent a mechanism for selectively regulating GLAST function in
      the mammalian nervous system.

PMID- 17179861
TI  - Clusterin enhances proliferation of primary astrocytes through extracellular
      signal-regulated kinase activation.
AB  - Clusterin, a secretory glycoprotein, has been shown to be up-regulated in the
      reactive astrocytes in response to brain injury and neurodegenerative diseases,
      but its function has not been clearly elucidated. In this study, we investigate
      whether clusterin has growth-stimulatory activity in astrocytes. Suppression of
      clusterin with antisense oligonucleotide induced growth arrest, whereas transient
      overexpression of clusterin by cDNA transfection or exogenous treatment with
      purified clusterin promoted proliferation of the primary astrocytes in culture.
      This clusterin-stimulated proliferation was abrogated by PD98059, an inhibitor of
      mitogen-activated protein kinase kinase. These results suggest that clusterin
      might play an important role in astrogliosis by stimulating the proliferation of
      astrocytes through activation of the extracellular signal-regulated kinase 1/2
      signaling pathway.

PMID- 17179862
TI  - Mechanisms of glutamate receptor induced proliferation of astrocytes.
AB  - Astrocytes express mainly metabotropic glutamate receptor 3 and metabotropic
      glutamate receptor 5 receptor subtypes, which show opposing effects on cellular
      proliferation upon activation. In this study, we investigated the mechanisms by
      which activation of these receptors modulates astrocyte proliferation. Activation
      of metabotropic glutamate receptor 5 with (S)-3,5-dihydroxyphenylglycine
      increased phospholipase D activity in astrocytes as well as astrocyte
      proliferation. The 3,5-dihydroxyphenylglycine-induced proliferation was inhibited
      in the presence of the metabotropic glutamate receptor 5 antagonist (2-methyl-6
      (phenylethynyl)pyridine), the protein kinase C inhibitor GF109203X, brefeldin A
      and 1-butanol. Activation of metabotropic glutamate receptor 3 with (2'S,2'R,3'R)
      2-(2',3'-dicarboxycyclopropyl)glycine-IV (DCG-IV) inhibited astrocyte
      proliferation without affecting metabotropic glutamate receptor 5-mediated
      phospholipase D activity. Metabotropic glutamate receptor 3 activation, however,
      only partially inhibited metabotropic glutamate receptor 5-mediated
      proliferation. In conclusion, metabotropic glutamate receptor 5 stimulates
      astrocyte proliferation via a protein kinase C-phospholipase D-phosphatidic acid
      dependent pathway, whereas metabotropic glutamate receptor 3-mediated inhibition
      of astrocyte proliferation does not involve phospholipase D, and is independent
      of metabotropic glutamate receptor 5-mediated effects.

PMID- 17179863
TI  - Alpha-synuclein potentiates Ca2+ influx through voltage-dependent Ca2+ channels.
AB  - Alpha-synuclein localized in synaptic terminals plays an important role in the
      pathogenesis of neurodegenerative diseases. The central domain of the protein,
      the nonamyloid component, is probably responsible for alpha-synuclein toxicity.
      Here, we report that alpha-synuclein and its nonamyloid component induced Ca2+
      influx in rat synaptoneurosomes. The effect of alpha-synuclein was eliminated by
      the N-type specific Ca2+ channel blocker, omega-conotoxin GVIA. The antioxidant,
      resveratrol, and the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine,
      did not prevent alpha-synuclein-induced Ca2+ influx. Our findings indicate that
      alpha-synuclein stimulated Ca2+ influx through N-type voltage-dependent Ca2+
      channels by a mechanism other than free radicals. A direct interaction between
      alpha-synuclein and N-type Ca2+ channels could be responsible for their effects
      on Ca2+ influx through voltage-dependent Ca2+ channels.

PMID- 17179864
TI  - Passive reactivation of background information from long-term memory during
      reading.
AB  - The present study examined the nature of background information activation in
      text reading with a moving-window technique, previously used in behavioral
      studies. We compared brain activation evoked by a locally coherent target
      sentence that was either consistent, qualified (conflict-then-consistent) or
      inconsistent with some background information in long-term memory. With a
      significantly longer reading time of the target sentence, the inconsistent
      condition showed greater brain activation in several cortical regions than did
      the consistent and the qualified conditions. Neither reading time nor brain
      activations showed any differences between the consistent and the qualified
      conditions. The results indicate that processing of a sentence in text reading
      involves passive reactivation of updated background information stored in long
      term memory, consistent with proposal from a 'here-and-now' theory.

PMID- 17179865
TI  - Cerebral networks for spontaneous and synchronized singing and speaking.
AB  - Singing in unison is usually easier than singing alone, but the neural mechanism
      underlying these two contrasting modes of singing remains unknown. We
      investigated neural correlates of singing by a functional magnetic resonance
      imaging study focusing on the capacities of spontaneity and synchronization and
      compared them with those of speaking. The left inferior frontal gyrus appears
      important for self-generation of text in singing and speaking without auditory
      input, whereas the left posterior planum temporale plays a key role in
      synchronizing both text and melody, in combination with the bilateral inferior
      parietal lobule for singing along, and with the left angular gyrus for speaking
      in chorus. These findings indicate that text and melody are not processed
      symmetrically or parallel in singing a well-learned song.

PMID- 17179866
TI  - Association of G72/G30 polymorphisms with early-onset and male schizophrenia.
AB  - To explore the effect of G72/G30 polymorphisms on the clinical manifestations of
      schizophrenia, especially on the age at onset and sex of patients, we examined
      three single nucleotide polymorphisms in 216 schizophrenic patients and 321
      healthy controls. Significant associations of schizophrenia with the A allele of
      rs947267 (P=0.012) and haplotype A-A-G (rs2391191-rs947267-rs778294) (P=0.008)
      were found in early-onset schizophrenic patients. So did the same allele
      (P=0.034) and haplotype (P=0.009) as mentioned above in male patients. These
      findings suggest that the G72/G30 gene may modulate the age at onset and there
      might be a potential interaction between this locus and sex in the pathogenesis
      of schizophrenia.

PMID- 17179867
TI  - Expression of p25 impairs contextual learning but not latent inhibition in mice.
AB  - The cyclin-dependent kinase 5 activator p25, which is derived from cleavage of
      p35, is thought to be formed in the brain of patients with Alzheimer's disease
      and schizophrenia. Female, but not male, transgenic mice expressing low levels of
      p25 have enhanced hippocampal long-term potentiation and improved spatial
      learning, raising the hypothesis that p25 may compensate for early learning
      deficits in Alzheimer's disease in a sex-dependent manner. Here, we show that low
      levels of p25 do not alter latent inhibition, a phenomenon that is impaired in
      patients with schizophrenia. We also demonstrate that contextual fear
      conditioning is impaired in female, but not in male, p25 transgenic mice. Thus,
      low levels of p25 are not always beneficial for learning as was previously
      hypothesized.

PMID- 17179868
TI  - The Parent-Teen Sexual Risk Communication Scale (PTSRC-III): instrument
      development and psychometrics.
AB  - BACKGROUND: Adolescents are a group at high risk for sexually transmitted
      infections (STIs), including the human immunodeficiency virus (HIV). Several
      parenting processes, including parental monitoring, support, role modeling, and
      sexual communication, have been shown to be significant influences of
      adolescents' sexual attitudes, beliefs, and behaviors. Parent-child sexual risk
      communication, in particular, has been associated significantly with adolescents'
      attitudes, beliefs, and behaviors related to risk of and prevention of STIs and
      HIV. OBJECTIVE: The aim of this study was to report on the development of the
      Parent-Teen Sexual Risk Communication Scale (PTSRC-III), an eight-item self
      report instrument for measuring the amount of communication about sexual risk and
      sexual risk reduction occurring between parents and their adolescent children, as
      reported by the adolescent. METHODS: Psychometrics of the PTSRC-III and the
      stability of the psychometric properties across two samples of late adolescents,
      college freshmen (N=95) and female licensed drivers aged 19 to 21 years (N=234),
      are reported. RESULTS: Internal reliability of the scale was excellent (alpha of
      >.93 and >.88 for sexual risk communication with mothers and fathers,
      respectively); test-retest reliability was acceptable (r=.88 and .79 over 2
      months for PTSRC with mothers and fathers, respectively). Concurrent validity,
      predictive validity, and stability of psychometrics were also demonstrated.
      Factor analysis demonstrated a two-factor structure. DISCUSSION: The PTSRC-III
      provides a valid and reliable measure for assessing female adolescents'
      perceptions of parent-teen sexual risk communication, particularly with their
      mothers. Psychometrics were shown to be stable across the two samples.
      Implications for use and future development are discussed.

PMID- 17179869
TI  - Anesthesia staffing and anesthetic complications during cesarean delivery: a
      retrospective analysis.
AB  - BACKGROUND: Obstetrical anesthesia services may be provided by Certified
      Registered Nurse Anesthetists (CRNAs), anesthesiologists, or a combination of the
      two providers. Research is needed to assist hospitals and anesthesia groups in
      making cost-effective staffing choices. OBJECTIVES: To identify differences in
      the rates of anesthetic complications in hospitals whose obstetrical anesthesia
      is provided solely by CRNAs compared to hospitals with only anesthesiologists.
      METHODS: Washington State hospital discharge data were obtained from 1993 to 2004
      for all cesarean sections, and were merged with a survey of hospital obstetrical
      anesthesia staffing. Anesthetic complications were identified via International
      Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)
      diagnosis codes. Resulting rates were risk-adjusted using regression analysis.
      RESULTS: Hospitals with CRNA-only staffing had a lower rate of anesthetic
      complications than those with anesthesiologist staffing (0.58% vs. 0.76%,
      p=.0006). However, after regression analysis, this difference was not significant
      (odds ratio for CRNA vs. anesthesiologist complications: 1.046 to 1, 95%
      confidence interval 0.649-1.658, p=.85). DISCUSSION: There is no difference in
      rates of complications between the two types of staffing models. As a result,
      hospitals and anesthesiology groups may safely examine other variables, such as
      provider availability and costs, when staffing for obstetrical anesthesia.
      Further study is needed to validate the use of ICD-9-CM codes for anesthesia
      complications as an indicator of quality.

PMID- 17179870
TI  - Motivational interviewing to increase physical activity in long-term cancer
      survivors: a randomized controlled trial.
AB  - BACKGROUND: Physical activity can confer many benefits on cancer survivors,
      including relief of persistent symptoms related to cancer treatment. OBJECTIVES:
      To evaluate the effect of a motivational interviewing (MI) intervention on
      increasing physical activity (Community Healthy Activities Model Program for
      Seniors questionnaire) and improving aerobic fitness (6-minute walk), health
      (Medical Outcomes Study Short-Form 36), and fatigue (Schwartz Cancer Fatigue
      Scale) in cancer survivors. A secondary purpose was to evaluate whether the
      effect of MI on physical activities depended on self-efficacy. METHODS: Fifty-six
      physically inactive adult cancer survivors (mean=42 months since completion of
      treatment) were assigned randomly to intervention and control groups. The MI
      intervention consisted of one in-person counseling session followed by two MI
      telephone calls over 6 months. Control group participants received two telephone
      calls without MI content. Outcomes were measured at baseline, 3 months, and 6
      months, and were analyzed using multilevel modeling. RESULTS: The results of the
      MI intervention explained significant group differences in regular physical
      activities (measured in caloric expenditure per week), controlling for time since
      completion of cancer treatment (p<.05). Aerobic fitness, physical and mental
      health, and fatigue were not different between groups. In the intervention group,
      individuals with high self-efficacy for exercise at baseline increased their
      physical activity more than those with low self-efficacy (p<.05). In the control
      group, increases in physical activity did not depend on self-efficacy.
      DISCUSSION: Use of MI may increase physical activity in long-term cancer
      survivors, especially in persons with high self-efficacy for exercise. Multilevel
      modeling analysis revealed individual changes that would not have been shown by
      analysis of group means. Future studies with larger samples or more intense MI
      interventions may show changes in aerobic fitness, physical and mental health,
      and fatigue.

PMID- 17179871
TI  - Complementary therapy and older rural women: who uses it and who does not?
AB  - BACKGROUND: Despite the growing use of complementary therapy by consumers in the
      United States, very little is known about the factors associated with the use of
      these therapies among older rural women. OBJECTIVE: The aim of this study was to
      answer the following research question using data from a portion of a larger
      study: What factors predict the use of complementary therapy among older rural
      women? METHODS: Data were collected by telephone interview from a random sample
      of older residents of 19 rural towns in Montana and North Dakota. Interviews were
      conducted using a guide that included questions about the use of allopathic and
      complementary healthcare and related issues such as health status, health
      problems, and reasons for seeking care. A direct logistic regression analysis was
      performed on the use of complementary or alternative medicine (CAM) as outcome
      and eight potential predictors. Data from 156 women were included in this
      analysis. RESULTS: A total of 25.6% (n=40) of the women reported using CAM in the
      recent past. Rural women most likely to use CAM were those who were fairly well
      educated, not currently married, and in their early older years. They had one or
      more significant chronic illnesses and lower health-related quality of life due
      to emotional concerns. DISCUSSION: By improving the existing understanding of who
      is or is not likely to use CAM, the results of this study can be used in giving
      comprehensive care for rural women, including all healthcare practices, self-care
      and practitioner provided, and complementary and conventional.

PMID- 17179872
TI  - Observation scales for pain assessment in older adults with cognitive impairments
      or communication difficulties.
AB  - BACKGROUND: Several pain observation scales have been developed to accurately
      assess and manage pain in older adults with severe cognitive impairments,
      communication difficulties, or both. OBJECTIVE: To review relevant pain
      observation scales and the psychometric qualities of these scales. METHODS: The
      literature was searched for articles reporting the use of a pain observation
      scale in an empirical study and describing psychometric properties in older
      adults with cognitive impairments, communication difficulties, or both. RESULTS:
      Thirteen pain observation scales were included. Scales differed in numbers of
      items, types of categories, and psychometric properties. Facial expression,
      vocalization, motor behavior, and social behavior or mood are categories present
      in most of the scales. In terms of reliability and validity, however, most
      studies are too limited or incomplete to allow definite conclusions to be drawn
      about usefulness in daily practice. DISCUSSION: As different methods of
      evaluating reliability and validity were used, and different aims (e.g., type of
      pain) were pursued, the available scales cannot be compared easily. Nevertheless,
      a few are promising, given preliminary results. These should be examined further
      on psychometric properties and usefulness in different populations because
      optimal pain assessment is necessary for efficient and effective pain treatment.

PMID- 17179873
TI  - Depression and anxiety in women with breast cancer and their partners.
AB  - BACKGROUND: Psychosocial interventions can improve psychological quality of life
      (symptoms of depression and anxiety) of both women with breast cancer and their
      partners, but are not offered routinely to women and their partners. OBJECTIVE:
      To test the hypotheses that telephone-delivered psychosocial interventions
      decrease depression and anxiety in women with breast cancer and their partners.
      METHODS: The design of the study was a three-wave repeated measures with a
      between-subjects factor (treatment group). Ninety-six women and their 96 partners
      were assigned randomly to participate in one of three different 6-week programs:
      (a) telephone interpersonal counseling (TIP-C); (b) self-managed exercise; or (c)
      attention control (AC). RESULTS: The mixed-model analysis of variance for
      symptoms of depression among women with breast cancer revealed women's depressive
      symptom scores decreased over time in all groups. For anxiety, women's symptoms
      of anxiety decreased in the TIP-C and exercise groups over time, but not in the
      AC group. A parallel set of analyses was conducted on partners' depression and
      anxiety data. Symptoms of depression and anxiety among the partners decreased
      substantially over the course of the investigation. Similar to the women,
      partners' symptoms of anxiety decreased significantly in the TIP-C and exercise
      groups, but not in the AC group. DISCUSSION: Findings from this study support
      that these telephone-delivered psychosocial interventions were effective for
      decreasing symptoms of depression and anxiety to improve psychological quality of
      life when compared to an AC group.

PMID- 17179874
TI  - Intervention research: establishing fidelity of the independent variable in
      nursing clinical trials.
AB  - BACKGROUND: Internal validity of a randomized clinical trial of a nursing
      intervention is dependent on intervention fidelity. Although several methods have
      been developed, evaluating audio or audiovisual tapes for prescribed and
      proscribed interventionist behaviors is considered the gold standard test of
      treatment fidelity. This approach requires development of a psychometrically
      sound instrument to meaningfully categorize and quantify interventionist
      behaviors. OBJECTIVE: To outline critical steps necessary to develop a treatment
      fidelity instrument. METHODS: A comprehensive literature review was conducted to
      determine procedures used by other researchers. The literature review produced
      five quantitative studies of treatment fidelity, all in the field of
      psychotherapy, and two replication studies. A synthesis of methodologies across
      studies combined with researchers' experiences resulted in identification of the
      steps necessary to develop a treatment fidelity measure. RESULTS: Seven
      sequential steps were identified as essential to the development of a valid and
      reliable measure of treatment fidelity. These steps include (a) identification of
      the essential elements of the experimental and control treatment modalities; (b)
      construction of scale items; (c) development of item scaling; (d) identification
      of the units for coding; (e) item testing and revision; (f) specification of
      rater qualifications and development of rater training program; and (g)
      development and completion of pilot testing to test psychometric properties.
      Development of the Possibilities Project Psychotherapy Coding Questionnaire is
      described as an illustration of the seven-step process. DISCUSSION: The results
      show the essential steps that are unique to the development of treatment fidelity
      measures and show the feasibility of using these steps to construct a
      psychometrically sound treatment-specific fidelity measure.

PMID- 17179875
TI  - Self-reported integration as a proxy for acculturation: a qualitative study.
AB  - BACKGROUND: It is essential to account for acculturation in any research
      conducted in multicultural populations. Both unidimensional and bidimensional
      approaches are used to measure the extent of acculturation; however, neither one
      of them is optimal. OBJECTIVE: To explore the immigrants' rating of the extent of
      their acculturation (self-reported integration) in contrast to an external
      (researchers') measurement. METHODS: Fifteen in-depth interviews with
      strategically sampled Russian-speaking men and women aged 25-70 years, with
      varying marital and employment status and living permanently in Stockholm,
      Sweden, were analyzed using a content analysis technique. The results were
      validated by means of a series of additional mini-interviews by telephone.
      RESULTS: The immigrants' self-reported integration corresponded with the
      researchers' bidimensional measurement of the extent of acculturation of these
      immigrants. Self-reported integration accounted for the mastering of the formal
      criteria of integration, resolving of grief concerning the homeland, and
      fulfilling the internal criteria of integration. DISCUSSION: Self-reported
      integration may be used as a proxy for acculturation but its application should
      be tested primarily in other settings and in a quantitative analysis.

PMID- 17179879
TI  - National plastic surgical nursing survey.
AB  - An understanding of the scope and nature of negative psychological complications
      resulting from plastic surgery is vital. This knowledge is essential to improve
      the complex interactions that patients experience as part of their surgical
      intervention. This is a national survey of patients' psychological complications
      reported by 312 board certified plastic surgical nurses. Perceived patient
      psychological complications were reported at a higher rate than perceived
      physical complications (p > .001), with peri-operative complications of anxiety
      and mild depression being most prevalent. Less frequent psychological
      complications included patient disappointment and severe depression. Not
      surprisingly, surgical site pain and nonspecific physical distress were the most
      frequent physical complications; sleep disturbance was common. Psychological
      complications occur at higher rates than do physical complications in plastic
      surgical practices. Patients with pre-existing psychological conditions are more
      at risk for peri-operative psychological complications. Nurses should be
      adequately prepared to screen, support, and coordinate psychological treatment
      for plastic surgery patients with the plastic surgeon.

PMID- 17179880
TI  - Discussing the relationship between quality care and cost-effective care in Swiss
      pediatric wound care.
AB  - The growing individual and public demand for high-quality care within a context
      of restricted budgets dominates the political as well as medical agenda. This
      demand for "quality care" has developed an "industry" and lobby relating to
      auditing practice even in the small subpopulation of pediatric surgical patients.
      With children, complex and nonhealing wounds are quite rare, but there are
      pressures to provide modern and high-quality wound care even in Switzerland.
      Thus, in accordance with practice in neighboring countries, guidelines for wound
      care have been established in the Swiss healthcare sector. Their validity and
      reliability in the context of cost-effective versus quality care are critically
      discussed in this paper.

PMID- 17179883
TI  - Patient simulation to enhance patient safety.

PMID- 17179881
TI  - Nursing implications for older adult patient education.

PMID- 17179884
TI  - The history of the American Society of Plastic and Reconstructive Surgical
      Nurses.

PMID- 17179885
TI  - Specialty support surfaces for the prevention and treatment of pressure ulcers.

PMID- 17179886
TI  - Informed consent.

PMID- 17179887
TI  - Malignant hyperthermia.

PMID- 17179889
TI  - Nursing certification: why it matters.

PMID- 17179892
TI  - Why is the study of iron important for magnetic resonance imaging?

PMID- 17179893
TI  - Role of iron in neurodegenerative disorders.
AB  - Although the pathophysiology underlying a number of neurodegenerative diseases is
      complex and, in many aspects, only partly understood, increased iron levels in
      pathologically relevant brain areas and iron-mediated oxidative stress seem to
      play a central role in many of them. Much has been learned from monogenetically
      caused disturbances of brain iron metabolism including pantothenate kinase
      associated neurodegeneration type 2, hereditary ferritinopathies affecting the
      basal ganglia, and aceruloplasminemia that may well be applied to the most common
      neurodegenerative disorders associated with brain iron accumulation including
      Parkinson disease and Alzheimer disease. Iron-mediated oxidative stress in
      neurodegenerative diseases caused by other genetic pathways like Huntington
      disease and Friedreich ataxia underscore the complex interaction of this trace
      metal and genetic variations. Therapeutical strategies derived from application
      of iron chelators in monogenetically caused disturbances of brain iron metabolism
      and new iron and oxidative stress diminishing substances in animal models of
      Parkinson disease are promising and warrant further investigational effort.

PMID- 17179894
TI  - Multispectral quantitative magnetic resonance imaging of brain iron stores: a
      theoretical perspective.
AB  - OBJECTIVES: To review published magnetic resonance imaging (MRI) iron
      quantification techniques in the context of quantitative MRI and MR relaxation
      theories. To analyze comparatively and as a function of age the simultaneous
      measurements of the proton density (PD), the relaxation times (T1 and T2), and
      the longitudinal to transverse relaxation times ratio (T1/T2) of brain regions
      known to accumulate iron preferentially. METHODS: Twenty-seven human subjects
      were scanned with the mixed turbo spin echo pulse sequence, which is
      multispectral in PD, T1, and T2. Quantitative MRI (Q-MRI) maps of PD, T1, T2, and
      T1/T2 were generated, and region of interest measurements were performed in 5
      brain regions, namely, frontal white matter (WM), genu of corpus callosum,
      caudate nucleus, putamen, and globus pallidus. RESULTS: Relaxation time
      measurements are consistent with results of others and provide further
      confirmation to our basic understanding of the relaxation effects of iron stores
      in the brain. Specifically, we found that the iron-rich globus pallidus exhibits
      enhanced T1 and T2 relaxation relative the iron poorer gray matter tissues
      (caudate nucleus and putamen) and also relative to the WM matter tissues (frontal
      WM and genu of the corpus callosum). We also observe that under riding this
      hypothesis-because we do not have independent confirmation-that iron caused
      relaxation enhancement, are the normal brain aging patterns, which suggest that
      the brain tissues become wetter with increasing age. Also noted is the virtual
      removal of age dependence observed for the T1/T2 ratio of WM tissues, further
      suggesting that this ratio may become of clinical significance in the diagnosis
      of neoplastic processes as well as for quantifying iron in tissue. CONCLUSIONS:
      The theoretical underpinnings of published brain iron Q-MRI techniques have been
      reviewed. We also examined MR relaxation theory essentials in relation to H
      proton relaxation phenomena in diamagnetic tissues as well as theoretical
      extensions to describe relaxation effects in tissues containing iron deposits
      with a focus on ferritin. Also reported are in vivo Q-MRI results of 27 human
      brains obtained with a multispectral technique that uses the mixed turbo spin
      echo pulse sequence and a model conforming Q-MRI algorithms.

PMID- 17179895
TI  - Magnetic resonance imaging of iron deposition in neurological disorders.
AB  - Deposition of iron in the brain is proposed to play a role in the pathophysiology
      of the normal aging process and neurodegenerative diseases. Whereas iron is
      required for normal neuronal metabolism, excessive levels can contribute to the
      formation of free radicals, leading to lipid peroxidation and neurotoxicity.
      Magnetic resonance imaging (MRI) is a powerful tool to detect excessive iron in
      the brain and longitudinally monitor changes in iron levels. Iron deposition is
      associated with a reduction in the T2 relaxation time, leading to hypointensity
      on spin-echo and gradient-echo T2-weighted images. The MRI changes associated
      with iron deposition have been observed both in normal aging and in various
      chronic neurological diseases, including multiple sclerosis, Alzheimer disease,
      and Parkinson disease. Magnetic resonance imaging metrics providing information
      about iron concentrations include R2, R2', and R2*. The purpose of this review is
      to discuss the role of iron and its detection by MRI in various neurological
      disorders. We will review the basic biochemical properties of iron and its
      influence on MRI signal. We will also summarize the sensitivity and specificity
      of MRI techniques in detecting iron. The MRI and pathological findings pertaining
      to brain iron will be reviewed with respect to normal aging and a variety of
      neurological disorders. Finally, the biochemistry and pathophysiology surrounding
      iron, oxidative stress, free radicals, and lipid peroxidation in the brain will
      be discussed, including therapeutic implications. The potential role of iron
      deposition and its assessment by MRI provides exciting potential applications to
      the diagnosis, longitudinal monitoring, and therapeutic development for disorders
      of the brain.

PMID- 17179896
TI  - High-field magnetic resonance imaging of brain iron in Alzheimer disease.
AB  - OBJECTIVES: Increased iron deposition in the brain may occur in several
      neurodegenerative diseases, including Alzheimer disease (AD). Iron deposits
      shorten T2 relaxation times on T2-weighted magnetic resonance (MR) images. Iron
      dependent contrast increases with magnetic field strength. We hypothesized that
      T2 mapping using 3 T MR imaging (MRI) can disclose differences between normal
      controls and AD subjects. METHODS: High-resolution brain imaging protocols were
      developed and applied to 24 AD patients and 20 age-matched controls using 3 T
      MRI. Eight anatomical regions of interest were manually segmented, and T2
      histograms were computed. A visual analysis technique, the heat map, was modified
      and applied to the large image data sets generated by these protocols. RESULTS: A
      large number (163) of features from these histograms were examined, and 38 of
      these were significantly different (P < 0.05) between the groups. In the
      hippocampus, evidence was found for AD-related increases in iron deposition
      (shortened T2) and in the concentration of free tissue water (lengthened T2).
      Imaging of a section of postmortem brain before and after chemically extracting
      the iron established the presence of MRI-detectable iron in the hippocampus,
      cortex, and white matter in addition to brain regions traditionally viewed as
      containing high iron concentrations.

PMID- 17179897
TI  - Sitagliptin (Januvia) for type 2 diabetes.

PMID- 17179898
TI  - Oral oxymorphone (Opana).

PMID- 17179899
TI  - Drugs for some common eye disorders.

PMID- 17179900
TI  - Investigation of the catalytic and structural roles of conserved histidines of
      human coproporphyrinogen oxidase using site-directed mutagenesis.
AB  - BACKGROUND: The catalytic contribution of four conserved histidines of human
      coproporphyrinogen oxidase (CPO) has been investigated using site-directed
      mutagenesis to change histidine (H) into alanine (A). MATERIAL/METHODS: The wild
      type and mutant enzyme forms were analyzed for their ability to utilize
      coproporphyrinogen-III, mesoporphyrinogen-VI, and harderoporphyrinogen as
      substrates. RESULTS: Wild-type CPO had specific activities of 4.9+/-0.9 nmole
      product/min/mg for coproporphyrinogen-III, 1.7+/-0.7 nmole product/min/mg for
      mesoporphyrinogen-VI, and 5.1+/-1.8 nmole product/min/mg for
      harderoporphyrinogen. The four mutant enzymes were catalytically competent with
      all three substrates, but to varying degrees. The most affected mutant was the
      H158A enzyme which exhibited approximately 50-fold lower activity than wild-type
      recombinant CPO. CONCLUSIONS: Thus, His158 of human CPO may have a role in the
      active site, but none of the conserved histidine residues of human
      coproporphyrinogen oxidase is essential for catalytic activity although changes
      in histidines have been implicated in the disease state hereditary
      coproporphyria.

PMID- 17179901
TI  - Importance of the autonomic nervous system in an experimental model of commotio
      cordis.
AB  - BACKGROUND: Young athletes may die suddenly when they are struck in the chest
      (commotio cordis). Proposed mechanisms of sudden death in commotio cordis include
      hypervagatonia and activation of the sympathetic nervous system. In an
      experimental model of commotio cordis, the importance of the sympathetic and
      parasympathetic nervous system in the initiation of ventricular fibrillation was
      evaluated. MATERIAL/METHODS: Juvenile swine weighing between 8 and 12 kg were
      anesthetized with ketamine and isoflurane and placed prone in a sling. Twenty
      animals were randomized to pretreatment with placebo or sympathetic and
      parasympathetic blockade. Chest blows were guided by echocardiography to the
      center of the left ventricle and animals received 1-3 strikes with a regulation
      baseball propelled at 30 mph and timed to impact 10-30 ms prior to the peak of
      the T-wave. RESULTS: With 17 impacts in 10 autonomically blocked animals, 6
      episodes of ventricular fibrillation were seen; with 15 impacts in 10 control
      animals, ventricular fibrillation occurred 6 times. There was also no significant
      difference between the groups in occurrence of nonsustained polymorphic
      ventricular tachycardia or ST elevation. Transient complete heart block was less
      commonly seen in animals treated with autonomic blockade, although this did not
      achieve statistical significance. CONCLUSIONS: In this experimental model of
      commotio cordis, autonomic blockade did not affect the frequency of sudden
      cardiac death, polymorphic ventricular tachycardia or ST segment elevation. Thus,
      vagotonic and sympathetic surges likely do not contribute to the syndrome of
      sudden death due to chest blows in young people and athletes.

PMID- 17179902
TI  - Apoptosis and proliferation of mesangial cells isolated from kidneys undergoing
      compensatory growth following contralateral nephrectomy: role of the renin
      angiotensin system.
AB  - BACKGROUND: Contralateral nephrectomy stimulates compensatory growth of the
      remaining kidney. Intensive growth is frequently associated with increased
      apoptosis. The proliferation and apoptosis of cultured rat mesangial cells
      isolated from the remaining kidney following contralateral nephrectomy were
      evaluated. The involvement of the renin-angiotensin system was concomitantly
      assessed. MATERIAL/METHODS: Apoptosis was assessed by TUNEL assay and hematoxylin
      staining, proliferation by (3)H-thymidine incorporation, angiotensin-II (A-II)
      production by RIA, bradykinin synthesis by specific EIA, and AT-1/AT-2 receptor
      mRNA expression by RT-PCR.( 125)I-A-II labeling was applied for AT-1/AT-2
      receptor density evaluation. RESULTS: Apoptosis of unstimulated control cultures
      progressively increased from a baseline of 2.02+/-0.55% to 8.3+/-1.19% in 30-min
      and 12.8+/-4.11% in 24-h cultures (p<0.0001 in each comparison), accompanied by
      augmented cell proliferation and both could be abolished by captopril treatment.
      Endogenous A-II synthesis was increased in postnephrectomy cultures. Exogenous A
      II enhanced apoptosis of control, but not of postnephrectomy cells. Bradykinin
      synthesis was elevated in cultures treated with captopril, but not with losartan
      or PD123319. AT-1 mRNA was increased 24 h following nephrectomy. Total A-II
      receptor density was decreased 30 min and 24 h following nephrectomy, while
      blockade of AT-1/AT-2 receptors was ineffective. CONCLUSIONS: 1. Contralateral
      nephrectomy stimulates apoptosis and proliferation of mesangial cells in the
      remaining kidney via increased endogenous A-II. 2. The mechanism by which A-II
      triggers apoptosis and proliferation of mesangial cells is not related to the AT
      1/AT-2 receptor pathway. 3. The effects of angiotensin-II can be abolished by ACE
      inhibition and are, at least in part, mediated via bradykinin activity.

PMID- 17179903
TI  - Regular egg consumption does not increase the risk of stroke and cardiovascular
      diseases.
AB  - BACKGROUND: We performed this study to examine the association between egg
      consumption and risk of cardiovascular diseases and mortality in a nationally
      representative cohort of 9734 adults aged 25 to 74 years. MATERIAL/METHODS: Egg
      consumption was categorized into no or less than 1 egg, 1 to 6 eggs, or greater
      than 6 eggs per week. Cox proportional hazards analysis was used to identify the
      relative risk (RR) of incident stroke, ischemic stroke, coronary artery disease
      and mortality over a 20-year follow-up in all participants and subsequently in
      diabetic participants. RESULTS: After adjusting for differences in age, gender,
      race, serum cholesterol level, body mass index, diabetes mellitus, systolic blood
      pressure, educational status and cigarette smoking, no significant difference was
      observed between persons who consumed greater than 6 eggs per week compared to
      those who consume none or less than 1 egg per week in regards to any stroke (RR,
      0.9; 95% confidence interval (CI), 0.7 to 1.1), ischemic stroke (RR, 0.9; 95% CI,
      0.7 to 1.1), or coronary artery disease (RR, 1.1; 95% CI, 0.9 to 1.3). In
      subgroup analysis among diabetics, consumption of greater than 6 eggs per week
      was associated with an increased risk of coronary artery disease (RR 2.0, 95% CI
      1.0-3.8). CONCLUSIONS: Consumption of greater than 6 eggs per week (average of 1
      egg or greater per day) does not increase the risk of stroke and ischemic stroke.
      The increased risk of coronary artery disease associated with higher egg
      consumption among diabetics warrants further investigations.

PMID- 17179904
TI  - Morphological changes of the upper gastrointestinal tract mucosa and Helicobacter
      pylori infection in HIV-positive patients with severe immunodeficiency and
      symptoms of dyspepsia.
AB  - BACKGROUND: HIV infection causes progressive immune defense system dysfunction,
      including the gastrointestinal (GI) tract. The aim of the study was to evaluate
      the morphological changes in the upper-GI tract mucosa in HIV-infected patients
      in relation to the degree of immunodeficiency, presence of H. pylori, fungal
      colonization, and antiretroviral treatment (HAART). MATERIAL/METHODS: One hundred
      forty-six patients (94 HIV positive, 52 HIV negative) with dyspeptic symptoms
      were evaluated by upper GI endoscopy and biopsy. The HIV-infected were divided
      into two groups: 47 patients with CD4+ count >200/mm(3) and 47 with severe
      immunodeficiency (CD4+ count <200/mm(3)); 42 of the total patients were treated
      with HAART. Gastric biopsies for histopathology and urease test, esophageal
      swabs, and gastric aspirates for mycological evaluation were taken. RESULTS: The
      HIV-infected patients with severe immunodeficiency had a lower prevalence of H.
      pylori infection and active chronic gastritis in the gastric antrum compared with
      the other HIV-infected patients and controls (H. pylori in 40%, 72%, and 69%,
      respectively; p<0.05). Mycotic esophagitis and mycotic colonization of the
      stomach were more frequent in patients with severe immunodeficiency. The
      prevalence of gastric mucosa changes was not different between the patients
      treated and not treated with HAART; H. pylori infection was less frequent in HIV
      infected patients treated with HAART (p<0.05). CONCLUSIONS: In severely
      immunodeficient patients with dyspeptic symptoms, the prevalence of H. pylori and
      active chronic gastritis in the gastric antrum is much lower than in HIV-negative
      patients. H. pylori infection is less frequent in patients treated with HAART.

PMID- 17179905
TI  - Thrombolytic therapy with urokinase for pulmonary embolism in patients with
      stable hemodynamics.
AB  - BACKGROUND: Thrombolytic agents such as urokinase have been used in the treatment
      of patients with massive pulmonary embolism and hypotension, but their effect in
      patients with submassive pulmonary embolism and normal blood pressure has been
      controversial. MATERIAL/METHODS: Urokinase (20,000 IU /kg) was intravenously
      administered to 36 patients who had pulmonary embolism and a normal blood
      pressure. This was followed by subcutaneous injection of a low-molecular-weight
      heparin for a week. RESULTS: Improvement in clinical symptoms and reduction in
      pulmonary pressure was observed in 28 (77.8%) patients within the first week of
      the thrombolytic therapy. The improvement rate in patients with embolic symptoms
      of less than 14 days, and in those who had symptoms between 14 and 30 days before
      the thrombolytic therapy was 86% and 50%, respectively (p<0.01). Non-life
      threatening bleeding complications were observed in 10 (22.2%) patients.
      CONCLUSIONS: Thrombolytic therapy with urokinase followed by low-molecular-weight
      heparin is an effective therapeutic strategy for patients with pulmonary embolism
      and stable haemodynamics. However, the long-term benefits of this strategy remain
      to be seen and further studies are warranted.

PMID- 17179906
TI  - Mechanism of gastric emptying through the pyloric sphincter: a human study.
AB  - BACKGROUND: The current view holds that gastric emptying is effected by the force
      of the antral peristaltic wave squeezing food particles through pyloric sphincter
      resistance. Whether this is accomplished by a reflex action was investigated.
      MATERIAL/METHODS: The study comprised 12 healthy volunteers (age: 42.2+/-10.6
      years). A balloon-tipped and a manometric tube were introduced into the stomach.
      Pressure responses in the proximal stomach, pyloric antrum, and pyloric sphincter
      to distension of the proximal stomach and of the antrum were recorded. Pyloric
      sphincter distension was induced to test its effect on antral and proximal
      stomach pressure. These tests were repeated in nine men after separately
      anesthetizing the pyloric antrum and sphincter. RESULTS: Distension of the
      proximal stomach produced no pressure changes in the proximal stomach, pyloric
      antrum, or sphincter (p>0.05). Antral distension effected a significant rise in
      antral pressure, but not in the proximal stomach. Significant sphincter pressure
      decrease occurred only with antral distension volumes >50 ml. Pyloric sphincter
      distension produced a significant rise in antral pressure, but not in the
      proximal stomach. Sphincteric or antral anesthetization produced no pressure
      changes in the pyloric sphincter, antrum, or proximal stomach. CONCLUSIONS:
      Pyloric sphincter relaxation upon antral distension implies a reflex relationship
      the authors call the "antro-sphincteric inhibitory reflex". Pyloric sphincter
      distension effected antral contraction, which is suggested to be a reflex in
      nature and which they term the "sphinctero-antral excitatory reflex". It is
      postulated that these two reflexes act to churn and transport gastric contents to
      the duodenum.

PMID- 17179907
TI  - Oxidant-antioxidant balance in patients with psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by
      pathological skin lesions due to various exogenous and endogenous factors and
      associated with a number of biochemical and immunological disturbances.
      Antioxidant enzymes may be involved in the pathogenesis of the disease. The aim
      of this study was to evaluate the concentration of lipid peroxidation products
      and glutathione peroxidase (GPx) activity in the blood of patients with psoriasis
      before and after treatment by conventional methods. MATERIAL/METHODS: The patient
      group consisted of 67 persons with psoriasis vulgaris who were treated at the
      Department and Clinic of Dermatology. The duration of the disease was from 3 to
      34 years. All patients were treated topically. The concentration of
      thiobarbituric acid reactive substances (TBARS) was determined in the blood
      plasma. The activity of GPx was determined in erythrocytes. RESULTS: In the
      healthy persons, GPx activity was 16.8+/-3.7 U/g Hb and TBARS concentration
      0.63+/-0.16 nmol MDA/ml of plasma. In the psoriasis patients, GPx activity in
      erythrocytes was 14.8+/-4.3 U/g Hb and TBARS concentration was 0.73+/-0.22 nmol
      MDA/ml of plasma before treatment. The applied external treatment caused
      improvement in the clinical state and a slow increase in GPx activity as well as
      a decrease in TBARS concentration to values comparable to those of the healthy
      volunteers. CONCLUSIONS: The results suggest that disorders in antioxidant
      defense mechanisms may play an important role in the pathogenesis of psoriasis.

PMID- 17179908
TI  - Incidence of cyclosporiasis in patients with gastrointestinal symptoms in western
      Turkey.
AB  - BACKGROUND: This study was designed to investigate the distribution of
      cyclosporiasis between October 2003 and October 2004 and the relationship between
      Cyclospora infection and seasonal as well as patient factors in western Turkey.
      MATERIAL/METHODS: Stool samples from 4660 immunocompetent patients with
      gastrointestinal symptoms and 326 immunocompetent patients with allergic symptoms
      from western Turkey were examined between October 2003 and October 2004 using wet
      preparation, formalin-ethyl acetate concentration, Trichrome stain, and modified
      Kinyoun's acid-fast staining methods. RESULTS: Twenty-three patients were found
      to be infected with Cyclospora oocysts. Parasites such as Cryptosporidium,
      Giardia intestinalis, Entamoeba histolytica/dispar, Blastocystis hominis and
      others were also observed. The incidence of cyclosporiasis was higher in summer
      and early autumn and most of the Cyclospora-infected patients were without
      diarrhea. CONCLUSIONS: Clinicians with patients from Turkey and abroad who have
      intestinal symptoms after visiting the country should be aware that Cyclospora
      infections could be considered as a possible cause of gastrointestinal symptoms
      in the absence of diarrhea in immunocompetent patients during the summer period
      in Turkey.

PMID- 17179909
TI  - The effect of Blastocystis hominis on the growth status of children.
AB  - BACKGROUND: B. hominis is a protozoan parasite commonly found in the human
      gastrointestinal tract. The pathogenesis of B. hominis is still controversial,
      although it is one of the most common parasites found in stool samples.
      MATERIAL/METHODS: This study was conducted at the Adnan Menderes Medical Faculty
      between January 2002 and June 2003 to evaluate the relationship between B.
      hominis and growth status in children in Aydin, Turkey. Healthy children with
      positive stool samples for B. hominis but negative for other parasites were
      selected as the case group (n=89). Two controls matched to each case by age and
      gender were selected by random sampling of children with negative stool samples
      for any parasite (n=178). RESULTS: The anthropometric measurements and body mass
      index were significantly lower in the case group than in the control group
      (p<0.05). CONCLUSIONS: According to this study there is a correlation between the
      presence of B. hominis and lower anthropometric indexes in children.

PMID- 17179910
TI  - The efficacy of hydrotalcite compared with OTC famotidine in the on-demand
      treatment of gastroesophageal reflux disease: a non-inferiority trial.
AB  - BACKGROUND: Antacids and gastric acid inhibitors are effective in the self
      treatment of gastroesophageal reflux disease (GERD). The aim was to investigate
      onset of action of the antacid hydrotalcite compared with the OTC H2-receptor
      antagonist famotidine in patients suffering from heartburn. MATERIAL/METHODS: A
      total of 53 patients with endoscopically diagnosed GERD grade 0-1 took part in
      this open, randomized, parallel-group comparison trial: 26 patients received a
      single dose of 1000 mg hydrotalcite and 27 patients a single dose of 10 mg
      famotidine on the occasion of a symptomatic reflux episode. Severity of heartburn
      and accompanying symptoms were documented on a four-point verbal rating scale
      (VRS) at baseline and up to four hours after intake. Onset and duration of action
      were defined by the number of patients experiencing improvement of heartburn from
      severe or moderate to mild or none compared with baseline. RESULTS: Hydrotalcite
      was significantly superior (p<0.001) to famotidine in increasing the proportion
      of responders within the first 45 minutes, starting 10 minutes after drug intake.
      Between 60 and 120 minutes, both compounds showed equal efficacy. Three hours
      after intake the response rate was 90.9% for hydrotalcite and 92.0% for
      famotidine. After four hours the response rates were 86.4% for hydrotalcite and
      96.0% for famotidine. In both groups, no adverse events were observed.
      CONCLUSIONS: The results indicate that hydrotalcite relieves the symptoms of
      gastroesophageal reflux faster than OTC famotidine and is equally effective for
      up to two hours. It is a safe and effective self-medication for on-demand
      treatment of heartburn.

PMID- 17179911
TI  - Combined spinal epidural analgesia for labor with and without 3 ml of 1.5%
      epidural lidocaine.
AB  - BACKGROUND: Lidocaine is used as a 'test dose' to detect misplacement of epidural
      catheters. When administered immediately after the initiation of a combined
      spinal epidural for labor analgesia, it was found to interfere with motor
      function. The authors hypothesized that an epidural test dose of 3 ml of 1.5%
      lidocaine injected immediately after the initiation of combined spinal epidural
      analgesia and followed by a continuous epidural infusion would prolong the
      duration of analgesia and decrease the incidence of breakthrough pain.
      MATERIAL/METHODS: Sixty nulliparous parturients were recruited for this
      randomized controlled trial. Combined spinal epidural analgesia was performed
      with intrathecal levobupivacaine 2.5 mg and fentanyl 25 microg. The patients were
      randomized into three groups: group L receiving 3 ml of 1.5% epidural lidocaine,
      group S 3 ml of normal saline, and group C the control group receiving no test
      solution. An epidural infusion of 0.1% levobupivacaine and 2 microg of
      fentanyl/ml at 10 ml/hr was initiated immediately. Their need for supplementary
      analgesia, duration of analgesia, sensory block, motor block, side-effects, and
      overall satisfaction were recorded. RESULTS: The breakthrough pain rate in all
      groups were similar. Their mean duration of analgesia (mean survival times) were
      not significantly different. Group C had the lowest incidence of lower limb motor
      block. The satisfaction scores were significantly highest in group L.
      CONCLUSIONS: The administration of epidural lidocaine and saline immediately
      after intrathecal levobupivacaine 2.5 mg and fentanyl 25 microg did not reduce
      the incidence of breakthrough pain in combined spinal epidural labor.

PMID- 17179912
TI  - Curious fatal intentional poisoning case with organophosphate pesticide.
AB  - BACKGROUND: A case of organophosphorus intoxication with rebounding symptoms is
      reported. CASE REPORT: Case report of a 24-year-old man who poisoned himself with
      organophosphorus pesticide and was hospitalized in a 22-bed adult medical
      surgical intensive care unit at a tertiary care hospital. The patient had
      ingested organophosphorus pesticide after an argument and fight with his family
      and had presented typical clinical and biological manifestations of intoxication
      by this chemical. He was treated by mechanical ventilation, large fluid infusion,
      gastric lavage, as well as atropine and pralidoxime. After 48 hours of intensive
      care, the patient improved considerably, but shortly after this improvement,
      mental, hemodynamic, and respiratory status altered again. Gastric fibroscopy
      showed a small plastic bag containing powder in the stomach which was responsible
      for the rebounding symptoms of the intoxication. CONCLUSIONS: Gastric fibroscopy
      can be helpful in case of organophosphorus intoxication with persistent or
      rebounding symptoms.

PMID- 17179913
TI  - Multimodality imaging features in a case of bronchial carcinoid including FDG
      PET.
AB  - BACKGROUND: Pulmonary carcinoid tumors are rare, low-grade neuroendocrine
      malignancies which comprise 1-2% of all lung neoplasms. Approximately 80% of
      carcinoid tumors occur in the central airways and present clinically as
      obstructive pneumonia or hemoptysis. Experience with F18 FDG PET to image
      pulmonary carcinoid tumors is limited. CASE REPORT: A 67 year old woman presented
      with two episodes of hemoptysis within one month. A whole body FDG PET scan was
      performed in addition to a contrast enhanced chest CT, a whole body In111
      octreotide scan, and quantitative lung perfusion scan during the diagnostic
      evaluation. An endobronchial lesion was discovered and the patient underwent a
      successful resection of the right middle and lower lobes. The histopathology of
      the lesion was consistent with a typical carcinoid tumor. CONCLUSIONS: We
      describe multimodality imaging findings along with the histopathology and a
      review of the literature, focusing on the role of FDG PET in the management of
      patients with bronchial carcinoid tumors.

PMID- 17179914
TI  - Atypical features of dementia in a patient with Creutzfeldt-Jakob disease.
AB  - BACKGROUND: This article describes a Polish patient (female, right-handed, age 68
      at onset) diagnosed with the Heidenhain variant of Creutzfeldt-Jakob Disease
      (HvCJD), characterized clinically by isolated visual disturbances with no ocular
      dysfunction prior to the development of myoclonus and other symptoms of CJD. CASE
      REPORT: Nothing in the history pointed to iatrogenic or acquired CJD, and genetic
      testing ruled out familial CJD. The neuroradiological picture (MRI) showed non
      specific features of cerebral atrophy (cortical and subcortical). An EEG revealed
      periodic triphasic sharp waves, particularly in the occipital lobes, and
      myoclonus occurring synchronically with generalized periodic epileptiform
      discharges. Comprehensive neuropsychological testing documented rapidly
      progressive dementia, with dysgraphia and aphasia deteriorating to organic
      mutism. Post-mortem neuropathological examination confirmed spongiform
      encephalopathy, especially in occipital cortex, with amyloid plaques but without
      neurofibrillary tangles. CONCLUSIONS: Over the crucial 6-week period the patient
      went from "Mild Cognitive Impairment" to a status resembling the final stages of
      Alzheimer's disease, without any evidence of a CVA. The only aspect of this case
      that does not fit the usual criteria for the Heidenhain variant is the fact that
      the patient survived over a year in a persistent vegetative state.
      Ophthalmologists and family physicians should be aware of the possibility of
      HvCJD in any patient over 60 presenting with otherwise inexplicable visual
      disturbances in the absence of significant ocular pathology, even when other
      symptoms of dementia may not be immediately noticeable.

PMID- 17179915
TI  - Stem cells from non-viable versus post-mortem tissues.

PMID- 17179916
TI  - Targets for antiepileptic drugs in the synapse.
AB  - Antiepileptic drugs (AEDs) have many proposed mechanisms of action and are still
      not fully understood. AEDs are widely used today to treat epilepsy, migraine,
      neuropathic pain, and bipolar disorder, and other disorders are also being
      investigated. The focus in this review is the main targets for AEDs in the
      GABAergic and glutamatergic synapses and possible future sites of action for AEDs
      to clarify their wide spectrum of activity. The study is a review of recently
      published investigations of the mechanisms of action of AEDs. The main targets
      for AEDs in the synapses include enhancement of GABAergic inhibitory
      neurotransmission, decrease in glutamatergic excitatory neurotransmission
      directly or via inhibition of voltage-dependent sodium and calcium channels, and
      interference with intracellular signaling pathways. Vigabatrin, tiagabine, and
      valproate possess their main actions in the GABAergic synapse. Levetiracetam,
      topiramate, lamotrigine, carbamazepine, oxcarbazepine, gabapentin, pregabalin,
      felbamate, and zonisamide decrease glutamatergic excitability. In addition,
      valproate, carbamazepine, and oxcarbazepine modulate intracellular signaling
      pathways. Several AEDs of a new generation based on the existing drugs are in
      development. Future targets to decrease excitability may include GABA and
      glutamate ionotropic and metabotropic receptors and astrocytes. Knowledge of the
      sites of action of AEDs in the synapse is important to improve our understanding
      of their broad spectrum of clinical efficacy and to develop future effective
      drugs for the treatment of both epilepsy and other neurological and psychiatric
      disorders.

PMID- 17179917
TI  - High fat diet modulation of glucose sensing in the beta-cell.
AB  - Type 2 diabetes is primarily associated with beta-cell failure, insulin
      resistance and elevated hepatic glucose production. The islet beta-cell is
      specialized for the synthesis, storage and secretion of insulin. Beta-cell
      failure is characterized by the inability of the beta-cell to secrete sufficient
      insulin in response to glucose, which ultimately results in hyperglycemia- the
      clinical hallmark of Type 2 diabetes. Impairment in glucose sensing contributes
      to beta-cell dysfunction. The facilitative glucose transporter, GLUT-2, and
      glucose phosphorylating enzyme, glucokinase, are key for glucose sensing of the
      pancreatic beta-cell, the initial event in the pathway for glucose-stimulated
      insulin secretion. There is an increase in dietary fat intake, particularly
      saturated fat, in both the developing and Westernized world, which predisposes
      individuals to become obese and to potentially develop insulin resistance, beta
      cell dysfunction and Type 2 diabetes. A high fat diet is known to reduce both
      GLUT-2 and glucokinase expression thereby impairing glucose-stimulated insulin
      secretion. Furthermore, a high fat diet and specific free fatty acids, induces
      oxidative stress and apoptosis which reduces beta-cell mass and compromises beta
      cell function. Glucose sensing is the initial event of glucose-stimulated insulin
      secretion therefore it is imperative to maintain adequate expression levels of
      GLUT-2 and GK for ensuring normal beta-cell function. The development of
      pharmaceutical agents that improve glucose-stimulated insulin secretion may
      replenish expression of these glucose sensing genes after their attenuation by
      high fat feeding.

PMID- 17179918
TI  - The secular trend of body weight of Greek schoolchildren in the 20th century.
AB  - BACKGROUND: Improvements in socioeconomic conditions in the 20th century had a
      dramatic impact on the growth and development of children, resulting in greater
      somatic growth and earlier pubertal maturation. Furthermore, in the last part of
      that century childhood obesity took on epidemic proportions in many countries The
      aim of the study was to present the secular trend of body weight of Greek
      schoolchildren in the 20th century. MATERIAL/METHODS: The data were taken from
      growth studies the authors conducted themselves or were able to find in the Greek
      literature. All studies were cross-sectional and spanned the years from 1920 to
      1995. The studies referred mainly to children living in Athens or other major
      cities of the country. RESULTS: The data were taken from growth studies the
      authors conducted themselves or were able to find in the Greek literature. All
      studies were cross-sectional and spanned the years from 1920 to 1995. The studies
      referred mainly to children living in Athens or other major cities of the
      country. CONCLUSIONS: Improvement in the socioeconomic conditions in Greece
      resulted in an increase in body weight in Greek schoolchildren in the 20th
      century. However, this increase tended to stop in adolescent girls.

PMID- 17179921
TI  - Islet transplantation for type 1 diabetes--where should we go?

PMID- 17179919
TI  - Hormesis, epitaxy, the structure of liquid water, and the science of homeopathy.
AB  - According to the western medical establishment, homeopathy is both "unscientific"
      and "implausible". A short overview of its history and the methods it uses,
      however, easily reveals that homeopathy is a true science, fully grounded on the
      scientific method and on principles, such as, among others, the Arndt-Schultz
      law, hormesis, and epitaxy, whose plausibility has been clearly and definitely
      demonstrated in a number of scientific publications and reports. Through a review
      of the scientific literature, an explanation of the basic principles of
      homeopathy is proposed based on arguments and evidence of mainstream science to
      demonstrate that, in spite of the claims of conventional medicine, homeopathy is
      both scientific and plausible and that there is no reasonable justification for
      its rejection by the western medical establishment. Hopefully, this hurdle will
      be overcome by opening academic institutions to homeopathy to enlarge the
      horizons of medical practice, recover the value of the human relationship with
      the patient, and through all this, offer the sick a real alternative and the
      concrete perspective of an improved quality of life.

PMID- 17179922
TI  - Severe iatrogenic hypoglycemia in type 2 diabetes mellitus.

PMID- 17179923
TI  - Are antihypertensive drugs associated with an increased risk of incident type 2
      diabetes?

PMID- 17179924
TI  - Clinical and public health implications of glycemic relapse in type 2 diabetes.

PMID- 17179925
TI  - How prevalent are diabetes-related complications in patients with youth-onset
      type 2 diabetes mellitus?

PMID- 17179926
TI  - The neuropathic diabetic foot.
AB  - Diabetic foot problems are common throughout the world, and result in major
      medical, social and economic consequences for the patients, their families, and
      society. Foot ulcers are likely to be of neuropathic origin and, therefore, are
      eminently preventable. Individuals with the greatest risk of ulceration can
      easily be identified by careful clinical examination of their feet: education and
      frequent follow-up is indicated for these patients. When infection complicates a
      foot ulcer, the combination can be limb-threatening, or life-threatening.
      Infection is defined clinically, but wound cultures assist in identification of
      causative pathogens. Tissue specimens are strongly preferred to wound swabs for
      wound cultures. Antimicrobial therapy should be guided by culture results, and
      although such therapy may cure the infection, it does not heal the wound.
      Alleviation of the mechanical load on ulcers (offloading) should always be a part
      of treatment. Plantar neuropathic ulcers typically heal in 6 weeks with
      nonremovable casts, because pressure at the ulcer site is mitigated and
      compliance is enforced. The success of other approaches to offloading similarly
      depends on the patient's adherence to the strategy used for pressure relief.

PMID- 17179927
TI  - The changing costs and benefits of screening for asymptomatic coronary heart
      disease in patients with diabetes.
AB  - Aggressive medical therapy can be justified in most patients with diabetes, but
      there may be some higher-risk asymptomatic patients who could benefit from
      revascularization and/or medical therapy for myocardial ischemia. Silent
      myocardial ischemia (SMI) might be used to identify these high-risk individuals.
      In this Review we define SMI as objective evidence of ischemia from any
      noninvasive test occurring in an asymptomatic patient. We outline what is known
      about asymptomatic coronary heart disease (CHD) in diabetes and how this relates
      to SMI. We examine how SMI predicts angiographic CHD and CHD events, and we
      describe the changing role of CHD screening as reflected by various guidelines.
      We identify the recent research suggesting that there may be substantial numbers
      of high-risk asymptomatic patients who have diabetes with undiagnosed CHD and who
      could benefit from more-active intervention; however, with the recent advances in
      medical therapy, and the uncertain benefits of screening, current guidelines
      strongly discourage this practice, except in limited clinical situations, such as
      before major surgery. Carefully conducted clinical trails using state-of-the-art
      investigations and therapy in well-characterized patients with diabetes are
      urgently required to inform physicians on when and how to intervene.

PMID- 17179928
TI  - Fulminant type 1 diabetes: a novel clinical entity requiring special attention by
      all medical practitioners.
AB  - Fulminant type 1 diabetes is a recently discovered subtype of type 1 diabetes. It
      is defined as diabetes in which the process of beta-cell destruction and the
      progression of hyperglycemia and ketoacidosis are extremely rapid. The
      pathogenesis of this disease remains to be clarified, but the involvement of both
      genetic background-especially human leukocyte antigen genes-and viruses has been
      suggested. Fulminant type 1 diabetes has the following clinical characteristics:
      duration of hyperglycemic symptoms is 4 days on average; there is a high
      prevalence of preceding common-cold-like and gastrointestinal symptoms; there is
      a near-normal level of glycated hemoglobin in spite of very high plasma glucose
      levels associated with ketoacidosis; the disease is sometimes related to
      pregnancy; and there are increased serum pancreatic enzyme levels, absent C
      peptide levels, but virtually no detectable autoantibodies against constituents
      of pancreatic beta cells. The presence of the above characteristics strongly
      indicates the diagnosis of fulminant type 1 diabetes. Once the diagnosis of this
      disease is suspected, treatment of diabetic ketoacidosis must be started
      immediately, as in all other cases of type 1 diabetes. Otherwise, the death of
      the patient is likely to occur within 24 h. All medical practitioners must
      remember that this extremely rapidly progressing type of diabetes does exist, and
      they must pay special attention not to overlook it.

PMID- 17179929
TI  - Mechanisms of Disease: endothelial dysfunction in insulin resistance and
      diabetes.
AB  - Endothelial dysfunction is one manifestation of the many changes induced in the
      arterial wall by the metabolic abnormalities accompanying diabetes and insulin
      resistance. In type 1 diabetes, endothelial dysfunction is most consistently
      found in advanced stages of the disease. In other patients, it is associated with
      nondiabetic insulin resistance and probably precedes type 2 diabetes. In obesity
      and insulin resistance, increased secretion of proinflammatory cytokines and
      decreased secretion of adiponectin from adipose tissue, increased circulating
      levels of free fatty acids, and postprandial hyperglycemia can all alter gene
      expression and cell signaling in vascular endothelium, cause vascular insulin
      resistance, and change the release of endothelium-derived factors. In diabetes,
      sustained hyperglycemia causes increased intracellular concentrations of glucose
      metabolites in endothelial cells. These changes cause mitochondrial dysfunction,
      increased oxidative stress, and activation of protein kinase C. Dysfunctional
      endothelium displays activation of vascular NADPH oxidase, uncoupling of
      endothelial nitric oxide synthase, increased expression of endothelin 1, a
      changed balance between the production of vasodilator and vasoconstrictor
      prostanoids, and induction of adhesion molecules. This review describes how these
      and other changes influence endothelium-dependent vasodilation in patients with
      insulin resistance and diabetes. The clinical utility of endothelial function
      testing and future therapeutic targets is also discussed.

PMID- 17179930
TI  - Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in
      neonates.
AB  - Hyperinsulinism is the single most common mechanism of hypoglycemia in neonates.
      Dysregulated insulin secretion is responsible for the transient and prolonged
      forms of neonatal hypoglycemia, and congenital genetic disorders of insulin
      regulation represent the most common of the permanent disorders of hypoglycemia.
      Mutations in at least five genes have been associated with congenital
      hyperinsulinism: they encode glucokinase, glutamate dehydrogenase, the
      mitochondrial enzyme short-chain 3-hydroxyacyl-CoA dehydrogenase, and the two
      components (sulfonylurea receptor 1 and potassium inward rectifying channel,
      subfamily J, member 11) of the ATP-sensitive potassium channels (K(ATP)
      channels). K(ATP) hyperinsulinism is the most common and severe form of
      congenital hyperinsulinism. Infants suffering from K(ATP) hyperinsulinism present
      shortly after birth with severe and persistent hypoglycemia, and the majority are
      unresponsive to medical therapy, thus requiring pancreatectomy. In up to 40-60%
      of the children with K(ATP) hyperinsulinism, the defect is limited to a focal
      lesion in the pancreas. In these children, local resection results in cure with
      avoidance of the complications inherent to a near-total pancreatectomy.
      Hyperinsulinism can also be part of other disorders such as Beckwith-Wiedemann
      syndrome and congenital disorders of glycosylation. The diagnosis and management
      of children with congenital hyperinsulinism requires a multidisciplinary approach
      to achieve the goal of therapy: prevention of permanent brain damage due to
      recurrent hypoglycemia.

PMID- 17179932
TI  - Retrograde neuronal tracing with a deletion-mutant rabies virus.
AB  - We have constructed a deletion-mutant rabies virus encoding EGFP and find it to
      be an excellent tool for studying detailed morphology and physiology of neurons
      projecting to injection sites within the mammalian brain. The virus cannot spread
      beyond initially infected cells yet, unlike other viral vectors, replicates its
      core within them. The cells therefore fluoresce intensely, revealing fine
      dendritic and axonal structure with no background from partially or faintly
      labeled cells.

PMID- 17179933
TI  - Recombineering in Mycobacterium tuberculosis.
AB  - Genetic dissection of M. tuberculosis is complicated by its slow growth and its
      high rate of illegitimate recombination relative to homologous DNA exchange. We
      report here the development of a facile allelic exchange system by identification
      and expression of mycobacteriophage-encoded recombination proteins, adapting a
      strategy developed previously for recombineering in Escherichia coli.
      Identifiable recombination proteins are rare in mycobacteriophages, and only 1 of
      30 genomically characterized mycobacteriophages (Che9c) encodes homologs of both
      RecE and RecT. Expression and biochemical characterization show that Che9c gp60
      and gp61 encode exonuclease and DNA-binding activities, respectively, and
      expression of these proteins substantially elevates recombination facilitating
      allelic exchange in both M. smegmatis and M. tuberculosis. Mycobacterial
      recombineering thus provides a simple approach for the construction of gene
      replacement mutants in both slow- and fast-growing mycobacteria.

PMID- 17179934
TI  - Disentangling conformational states of macromolecules in 3D-EM through likelihood
      optimization.
AB  - Although three-dimensional electron microscopy (3D-EM) permits structural
      characterization of macromolecular assemblies in distinct functional states, the
      inability to classify projections from structurally heterogeneous samples has
      severely limited its application. We present a maximum likelihood-based
      classification method that does not depend on prior knowledge about the
      structural variability, and demonstrate its effectiveness for two macromolecular
      assemblies with different types of conformational variability: the Escherichia
      coli ribosome and Simian virus 40 (SV40) large T-antigen.

PMID- 17179935
TI  - SILENCE: a new forward genetic technology.
AB  - Silencing induced by long terminal repeat (LTR)-encoded cis-acting response
      element, termed SILENCE, is a forward genetic system that allows for conditional,
      epigenetic control of host-gene transcription. This new research tool is
      independent of gene mutation or disruption, does not require complementation, and
      conditional gene repression appears complete at the level of protein function.
      SILENCE functions in hypodiploid cells and is a platform technology with broad
      applications in gene discovery.

PMID- 17179936
TI  - MRI-based localization of electrophysiological recording sites within the
      cerebral cortex at single-voxel accuracy.
AB  - The localization of microelectrode recording sites in the layers of primate
      cerebral cortex permits the analysis of relationships between recorded neuronal
      activities and underlying anatomical connections. We present a magnetic resonance
      imaging method for precise in vivo localization of cortical recording sites. In
      this method, the susceptibility-induced effect thickens the appearance of the
      microelectrode and enhances the detectability of the microelectrode tip, which
      usually occupies less than a few percent of the volume of an image voxel. In a
      phantom study, the optimized susceptibility-induced effect allowed tip detection
      with single-voxel accuracy (in-plane resolution, 50 mum). We applied this method
      to recording microelectrodes inserted into the brains of macaque monkeys, and
      localized the microelectrode tip at an in-plane resolution of 150 mum within the
      cortex of 2-3 mm in thickness. Subsequent histological analyses validated the
      single-voxel accuracy of the in vivo tip localization. This method opens up a way
      to investigate information flow during cognitive processes in the brain.

PMID- 17179937
TI  - Major signal increase in fluorescence microscopy through dark-state relaxation.
AB  - We report a substantial signal gain in fluorescence microscopy by ensuring that
      transient molecular dark states with lifetimes >1 micros, such as the triplet
      state relax between two molecular absorption events. For GFP and Rhodamine dye
      Atto532, we observed a 5-25-fold increase in total fluorescence yield before
      molecular bleaching when strong continuous-wave or high-repetition-rate pulsed
      illumination was replaced with pulses featuring temporal pulse separation >1
      micros. The signal gain was observed both for one- and two-photon excitation.
      Obeying dark or triplet state relaxation in the illumination process signifies a
      major step toward imaging with low photobleaching and strong fluorescence fluxes.

PMID- 17179938
TI  - Accurate phylogenetic classification of variable-length DNA fragments.
AB  - Metagenome studies have retrieved vast amounts of sequence data from a variety of
      environments leading to new discoveries and insights into the uncultured
      microbial world. Except for very simple communities, the encountered diversity
      has made fragment assembly and the subsequent analysis a challenging problem. A
      taxonomic characterization of metagenomic fragments is required for a deeper
      understanding of shotgun-sequenced microbial communities, but success has mostly
      been limited to sequences containing phylogenetic marker genes. Here we present
      PhyloPythia, a composition-based classifier that combines higher-level generic
      clades from a set of 340 completed genomes with sample-derived population models.
      Extensive analyses on synthetic and real metagenome data sets showed that
      PhyloPythia allows the accurate classification of most sequence fragments across
      all considered taxonomic ranks, even for unknown organisms. The method requires
      no more than 100 kb of training sequence for the creation of accurate models of
      sample-specific populations and can assign fragments >or=1 kb with high
      specificity.

PMID- 17179939
TI  - Sensitive protein detection via triple-binder proximity ligation assays.
AB  - The detection of weakly expressed proteins and protein complexes in biological
      samples represents a fundamental challenge. We have developed a new proximity
      ligation strategy named 3PLA that uses three recognition events for the highly
      specific and sensitive detection of as little as a hundred molecules of the
      vascular endothelial growth factor (VEGF), the biomarkers troponin I, and
      prostate-specific antigen (PSA) alone or in complex with an inhibitor-
      demonstrating the versatility of 3PLA.

PMID- 17179940
TI  - Heart rate reduction by inhibition of If or by beta-blockade has different
      effects on postsystolic wall thickening.
AB  - BACKGROUND AND PURPOSE: Postsystolic wall thickening (PSWT) is part of thickening
      that occurs after end-systole and represents wasted effort as it does not
      contribute to ejection. The effects of antianginal drugs on PSWT remain to be
      established. We compared the effects on PSWT of two agents that reduce heart
      rate, the beta-blocker atenolol and the selective inhibitor of If current,
      ivabradine. EXPERIMENTAL APPROACH: Six dogs were prepared to measure wall
      thickening by sonomicrometry in the conscious state, at rest and during exercise,
      after administration of saline, atenolol (1 mg.kg-1) or ivabradine (1 mg.kg-1).
      KEY RESULTS: Atenolol and ivabradine similarly reduced heart rate vs saline at
      rest (about 10-20%) and during exercise (about 30%). Atenolol but not ivabradine
      decreased dP/dtmax. Concomitantly, PSWT increased with atenolol vs saline at rest
      (0.35+/-0.07 vs 0.21+/-0.03 mm, respectively) and during exercise (0.30+/-0.04 vs
      0.15+/-0.04 mm, respectively). In contrast, ivabradine did not alter PSWT.
      Importantly, atenolol but not ivabradine increased the ratio of postsystolic to
      systolic wall thickening by 80+/-23%. This enhanced thickening during diastole
      with atenolol was accompanied by impeded isovolumic relaxation of the left
      ventricle, as illustrated by the significant correlation between the isovolumic
      relaxation time constant tau and the postsystolic to systolic wall thickening
      ratio. None of these effects of atenolol were abolished when heart rate was
      controlled with atrial pacing. CONCLUSION AND IMPLICATIONS: For a similar heart
      rate reduction at rest and during exercise, ivabradine, but not atenolol, did not
      alter PSWT and preserved the part of thickening contributing to ejection.

PMID- 17179941
TI  - Comparative antagonist pharmacology at the native mouse bradykinin B2 receptor:
      radioligand binding and smooth muscle contractility studies.
AB  - BACKGROUND AND PURPOSE: The aim was to characterize the recently discovered non
      peptide antagonist MEN16132 at the mouse B2 receptor, relative to other
      antagonists. EXPERIMENTAL APPROACH: [3H]-BK binding experiments used mouse lung
      and ileum tissue membranes and antagonist potency was measured in the isolated
      ileum contractility assay. KEY RESULTS: Two BK binding sites resulted from
      saturation and homologous competition experiments. A role for the B1 receptor was
      excluded because of the poor affinity of B1 receptor ligands (pIC50<5). MEN16132,
      and the other reference antagonists, inhibited only one portion of BK specific
      binding, and the rank order of potency was (pIC50): Icatibant (lung 10.7; ileum
      10.2)=MEN11270 (lung 10.4; ileum 9.9)=MEN16132 (lung 10.5; ileum 9.9).>LF16-0687
      (lung 8.9; ileum 8.8)>FR173657 (lung 8.6; ileum 8.2). BK homologous curves
      performed with lung membranes after treatment with the antagonist MEN16132 or
      Icatibant (10 nM) displayed only the low affinity site. The functional antagonism
      by MEN16132 (pA2 9.4) and Icatibant (pA2 9.1), towards BK (control EC50 6.1 nM)
      induced ileum contractions, was concentration-dependent and surmountable, but the
      Schild plot slope was less than unity. CONCLUSIONS AND IMPLICATIONS: In mouse
      tissue, radiolabelled BK recognizes two binding sites and B2 receptor antagonists
      can compete only for the higher affinity one. The pharmacological profile of the
      novel non-peptide antagonist MEN16132 indicates that it exhibits subnanomolar
      affinity and potency for the mouse B2 receptor and is suitable for further
      characterization in in vivo pathophysiological models.

PMID- 17179942
TI  - Effects of budesonide on P-glycoprotein expression in intestinal cell lines.
AB  - BACKGROUND AND PURPOSE: P-glycoprotein (P-gp) is an important efflux transporter
      that supports the barrier function of the gut against invading antigens and
      against administered drugs. Since glucocorticoids, such as budesonide, are
      frequently used during inflammatory bowel disease we investigated how budesonide
      influences P-gp expression in different intestinal cell lines. EXPERIMENTAL
      APPROACH: LS180 and Caco-2 cells were incubated with budesonide and changes in P
      gp expression were determined on mRNA, protein and functional level. The mRNA
      expression levels of glucocorticoid receptor (GR) and pregnane X receptor (PXR)
      were determined in these cell lines. PXR receptor was transiently transfected
      into Caco-2 cells. KEY RESULTS: Budesonide showed an induction of P-gp in LS180
      cells and a down-regulation in Caco-2 cells. Expression levels of nuclear
      receptors revealed high expression of PXR only in LS180 cells and exclusive
      expression of GR in Caco-2 cells. Mifepristone, an anti-glucocorticoid, could not
      reverse the down-regulation of P-gp by budesonide in Caco-2 cells. In PXR
      transfected Caco-2 cells the budesonide-mediated down-regulation of P-gp was
      abolished. Furthermore the expression of cytochrome P450 3A4 (CYP3A4), another
      PXR target gene, was induced in PXR-transfected Caco-2 cells after budesonide
      treatment. CONCLUSIONS AND IMPLICATIONS: Budesonide has the potential to
      influence MDR1 expression in vitro. In LS180 cells, the induction of MDR1 by
      budesonide probably is mediated via PXR. The mechanism of the down-regulation in
      Caco-2 cells still remains unclear, but GR does not seem to be involved. Further
      studies are required to evaluate how budesonide alters P-gp expression in vivo.

PMID- 17179943
TI  - Inhibitors of phosphodiesterase 5 (PDE 5) inhibit the nerve-induced release of
      nitric oxide from the rabbit corpus cavernosum.
AB  - BACKGROUND AND PURPOSE: Nitrergic neurons are important for erectile responses in
      the corpus cavernosum and impaired signalling results in erectile dysfunction,
      today treated successfully by oral administration of the selective
      phosphodiesterase 5 (PDE 5) inhibitors sildenafil, tadalafil and vardenafil.
      Although the importance of nitrergic neurons in urogenital function has become
      evident, it has not been investigated if the PDE 5 inhibitors affect the nerve
      induced release of nitric oxide (NO). In a previous study we found that the
      soluble guanylate cyclase (sGC)/cyclic guanosine 3',5'-monophosphate (cGMP)
      pathway might modulate nerve-induced release of NO in isolated cavernous tissue.
      EXPERIMENTAL APPROACH: Electrical field stimulation (EFS 5 Hz, 40 V, 0.3 ms pulse
      duration, 25 pulses at intervals of 2 min) of rabbit isolated cavernous tissue
      elicited reproducible, nerve-mediated relaxations in the presence of scopolamine
      (10(-5) M), guanethidine (10(-5) M) and phenylephrine (3 x 10(-6) M). In
      superfusion experiments, nerve stimulation (20 Hz, 40 V, 1 ms) of the cavernous
      tissue evoked release of NO/NO2-, measured by chemiluminescence. KEY RESULTS:
      Sildenafil, tadalafil and vardenafil decreased the muscular tone and prolonged
      the relaxations to nerve stimulation. The evoked release of NO decreased to 72+/
      11%, 55+/-16% and 61+/-14% of control, respectively after addition of sildenafil,
      tadalafil or vardenafil (all 10(-4) M, n=6-8, p<0.05). CONCLUSIONS AND
      IMPLICATIONS: Selective PDE 5 inhibitors influence the nerve-induced release of
      NO, probably via cGMP-mediated negative feedback. This negative feedback might
      explain why priapism is not seen during monotherapy with the PDE inhibitors.

PMID- 17179944
TI  - The antinociceptive effects of intraplantar injections of 2-arachidonoyl glycerol
      are mediated by cannabinoid CB2 receptors.
AB  - BACKGROUND AND PURPOSE: 2-arachidonoyl glycerol (2-AG) is an endogenous
      cannabinoid with central antinociceptive properties. Its degradation is catalysed
      by monoacylglycerol lipase (MGL) whose activity is inhibited by URB602, a new
      synthetic compound. The peripheral antinociceptive effects of 2-AG and URB602 in
      an inflammatory model of pain are not yet determined. We have evaluated these
      effects with and without the cannabinoid CB(1) (AM251) and CB(2) (AM630) receptor
      antagonists. EXPERIMENTAL APPROACH: Inflammation was induced in rat hind paws by
      intraplantar injection of formalin. Nociception was assessed behaviourally over
      the next 60 min, in 19 experimental groups: (1) control; (2-6) 2-AG (0.01-100
      microg); (7) AM251 (80 microg); (8) AM251+2-AG (10 microg); (9) AM630 (25
      microg); (10) AM630+2-AG (10 microg); (11-16) URB602 (0.1-500 microg); (17) 2
      AG+URB602 (ED(50)); (18) AM251+URB602 (ED(50)); (19) AM630+URB602 (ED(50)). Drugs
      were injected s.c. in the dorsal surface of the hind paw (50 microl), 15 min
      before formalin injection into the same paw. KEY RESULTS: 2-AG and URB602
      produced dose-dependent antinociceptive effects for the late phases of the
      formalin test with ED(50) of 0.65+/-0.455 mug and 68+/-14.3 microg, respectively.
      Their combination at ED(50) doses produced an additive antinociceptive effect.
      These effects were inhibited by AM630 but not by AM251 for 2-AG and by the two
      cannabinoid antagonists for URB602. CONCLUSIONS AND IMPLICATIONS: Locally
      injected 2-AG and URB602 decreased pain behaviour in a dose-dependent manner in
      an inflammatory model of pain. The antinociceptive effect of 2-AG was mediated by
      the CB(2) receptor.

PMID- 17179945
TI  - Identification of an antagonist that selectively blocks the activity of
      prostamides (prostaglandin-ethanolamides) in the feline iris.
AB  - BACKGROUND AND PURPOSE: The prostamides (prostaglandin-ethanolamides) and
      prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the
      respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist
      studies suggest that their pharmacologies are unique and unrelated to prostanoid
      receptors. This concept was further investigated using antagonists. EXPERIMENTAL
      APPROACH: The isolated feline iris was used as a key preparation, where
      prostanoid FP receptors and prostamide activity co-exist. Activity at human
      recombinant FP and other prostanoid receptors was determined using stable
      transfectants. KEY RESULTS: In the feline iris, AGN 204396 produced a rightward
      shift of the dose-response curves for prostamide F2alpha and the prostamide
      F2alpha analog bimatoprost but did not block the effects of PGF2alpha and
      synthetic FP receptor agonists. Studies on human recombinant prostanoid receptors
      confirmed that AGN 204396 did not behave as a prostanoid FP receptor antagonist.
      AGN 204396 exhibited no antagonism at DP and EP1-4, but was a highly effective TP
      receptor antagonist. Contrary to expectation, the FP receptor antagonist AL-8810
      efficaciously contracted the cat iris. AGN 204396 did not affect AL-8810 induced
      contractions, demonstrating that AL-8810 and AGN 204396 are pharmacologically
      distinct. Unlike AL-8810, the ethylamide derivate of AL-8810 was not an agonist.
      Al-8810 did not block prostamide F2alpha activity. Finally, AGN 204396 did not
      block PGE2-glyceryl ester activity. CONCLUSIONS AND IMPLICATIONS: The ability of
      AGN 204396 to selectively block prostamide responses suggests the existence of
      prostamide sensitive receptors as entities distinct from receptors recognizing
      PGF2alpha and PGE2-glyceryl ester.

PMID- 17179946
TI  - A high throughput drug screen based on fluorescence resonance energy transfer
      (FRET) for anticancer activity of compounds from herbal medicine.
AB  - BACKGROUND AND PURPOSE: We report the development of a very efficient cell-based
      high throughput screening (HTS) method, which utilizes a novel bio-sensor that
      selectively detects apoptosis based on the fluorescence resonance energy transfer
      (FRET) technique. EXPERIMENTAL APPROACH: We generated a stable HeLa cell line
      expressing a FRET-based bio-sensor protein. When cells undergo apoptosis, they
      activate a protease called 'caspase-3'. Activation of this enzyme will cleave our
      sensor protein and cause its fluorescence emission to shift from a wavelength of
      535 nm (green) to 486 nm (blue). A decrease in the green/blue emission ratio thus
      gives a direct indication of apoptosis. The sensor cells are grown in 96-well
      plates. After addition of different chemical compounds to each well, a
      fluorescence profile can be measured at various time-points using a fluorescent
      plate reader. Compounds that can trigger apoptosis are potential candidates as
      anti-cancer drugs. KEY RESULTS: This novel cell-based HTS method is highly
      effective in identifying anti-cancer compounds. It was very sensitive in
      detecting apoptosis induced by various known anti-cancer drugs. Further, this
      system detects apoptosis, but not necrosis, and is thus more useful than the
      conventional cell viability assays, such as those using MTT. Finally, we used
      this system to screen compounds, isolated from two plants used in Chinese
      medicine, and identified several effective compounds for inducing apoptosis.
      CONCLUSIONS AND IMPLICATIONS: This FRET-based HTS method is a powerful tool for
      identifying anti-cancer compounds and can serve as a highly efficient platform
      for drug discovery.

PMID- 17179947
TI  - Suberosin inhibits proliferation of human peripheral blood mononuclear cells
      through the modulation of the transcription factors NF-AT and NF-kappaB.
AB  - BACKGROUND AND PURPOSE: Extracts of Plumbago zeylanica containing suberosin
      exhibit anti-inflammatory activity. We purified suberosin from such extracts and
      studied its effects on a set of key regulatory events in the proliferation of
      human peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin
      (PHA). EXPERIMENTAL APPROACH: Proliferation of PBMC in culture was measured by
      uptake of 3H-thymidine; production of cytokines and cyclins by Western blotting
      and RT-PCR. Transcription factors NF-AT and NF-kappaB were assayed by
      immunocytochemistry and EMSA. KEY RESULTS: Suberosin suppressed PHA-induced PBMC
      proliferation and arrested cell cycle progression from the G1 transition to the S
      phase. Suberosin suppressed, in activated PBMC, transcripts of interleukin-2 (IL
      2), interferon-gamma (IFN-gamma), and cyclins D3, E, A, and B. DNA binding
      activity and nuclear translocation of NF-AT and NF-kappaB induced by PHA were
      blocked by suberosin. Suberosin decreased the rise in intracellular Ca2+
      concentration ([Ca2+]i) in PBMC stimulated with PHA. Suberosin did not affect
      phosphorylation of p38 and JNK but did reduce activation of ERK in PHA-treated
      PBMC. Pharmacological inhibitors of NF-kappaB, NF-AT, and ERK decreased
      expression of mRNA for the cyclins, IL-2, and IFN-gamma and cell proliferation in
      PBMC activated by PHA. CONCLUSIONS AND IMPLICATIONS: The inhibitory effects of
      suberosin on PHA-induced PBMC proliferation, were mediated, at least in part,
      through reduction of [Ca2+]i, ERK, NF-AT, and NF-kappaB activation, and early
      gene expression in PBMC including cyclins and cytokines, and arrest of cell cycle
      progression in the cells. Our observations provide an explanation for the anti
      inflammatory activity of P. zeylanica.

PMID- 17179948
TI  - Antagonist, partial agonist and antiproliferative actions of B-9870 (CU201) as a
      function of the expression and density of the bradykinin B1 and B2 receptors.
AB  - BACKGROUND AND PURPOSE: A bradykinin (BK) B2 receptor (B2R) antagonist, B-9870
      (CU201), has been proposed to behave as a 'biased agonist' at B2Rs and to exert
      anti-neoplasic effects. It was unclear whether these effects were determined by
      the activation of B2Rs by the drug. B-9870 was evaluated for antagonism or
      stimulation of several responses mediated by the rabbit B2R or B1 receptor (B1R);
      its anti-proliferative activity was also characterized. EXPERIMENTAL APPROACH AND
      KEY RESULTS: B-9870 was an insurmountable B2R antagonist in the rabbit jugular
      vein contractility assay, but a partial agonist in HEK 293 cells expressing the
      rabbit B2R or a green fluorescent protein (GFP) conjugate of the latter (ERK1/2
      phosphorylation, [Ca2+]i, [3H]-arachidonate release, endocytosis). The agonist
      like effects of B-9870 were inhibited by the B2R antagonist LF 16.0687 and absent
      in untransfected cells. In addition, B-9870 was a surmontable antagonist of the
      rabbit B1R in the aorta contractility assay, and blocked Lys-des-Arg9-BK-induced
      ERK1/2 phosphorylation in HEK 293 cells expressing a fluorescent B1R conjugate. B
      9870 inhibited the growth of MDA-MB-231 cells. The latter effect was not
      influenced by B1R or B2R antagonists and was not apoptotic. MDA-MB-231 cells
      expressed a small population of B2Rs but no B1Rs; they responded to BK (small
      calcium transients) and B-9870 behaved as an antagonist. CONCLUSION AND
      IMPLICATIONS: B-9870 is a dual B1R and B2R antagonist with confirmed stimulating
      effects at the B2R in high expression systems only. Its cell type-specific anti
      proliferative effect occurs at a high concentration, independently from kinin
      receptors and apoptosis.

PMID- 17179949
TI  - Do studies in caveolin-knockouts teach us about physiology and pharmacology or
      instead, the ways mice compensate for 'lost proteins'?
AB  - A wide array of phenotypic changes have been reported in mice with knockout of
      expression of caveolin-1. Neidhold et al. (2007) describe results in this issue
      that continue this trend by showing that saphenous arteries from adult caveolin-1
      knockout mice lack caveolae, lose beta1-adrenoceptor-promoted relaxation, gain
      beta3-adrenoceptor-promoted relaxation but show no change in vasomotor response
      to beta2-adrenoceptor activation. Neither the physiological importance for wild
      type animals nor the mechanistic basis for these changes is clear. Although the
      caveolin-1 knockout and wild-type mice express similar levels of the receptor
      mRNAs, the protein expression of the receptors is not specified and represents,
      in our view, an important limitation of the study. We also question the
      physiological relevance of the findings and ask: Do studies in total
      body/lifespan caveolin-knockout mice further understanding of physiology and
      pharmacology or do they primarily characterize secondary consequences? We propose
      that alternative approaches that decrease caveolin expression in a temporally and
      spatially discrete manner are more likely to facilitate definitive conclusions
      regarding caveolin-1 and its role in regulation of beta-adrenoceptors and other
      pharmacological targets.

PMID- 17179950
TI  - The function of alpha- and beta-adrenoceptors of the saphenous artery in caveolin
      1 knockout and wild-type mice.
AB  - BACKGROUND AND PURPOSE: Adrenoceptors can associate with cardiac caveolae. To
      investigate the function of vascular caveolae, adrenoceptor-mediated effects were
      compared in the saphenous artery of caveolin-1 knockout (cav-1KO) and wild-type
      (WT) mice. EXPERIMENTAL APPROACH: Electronmicroscopy was used to detect caveolae.
      Real-Time quantitative PCR was used for adrenoceptor subtypes. Catecholamine
      evoked contractions and relaxations were studied in arterial segments. KEY
      RESULTS: Caveolae were found in arterial smooth muscle from WT but not from cav
      1KO mice. Arterial mRNA levels for the adrenoceptors alpha1A, alpha1B, alpha1D,
      beta1, beta2 and beta3 were similar in cav-1KO and WT. (-)-Noradrenaline
      contracted cav-1KO (-log EC50M=7.1) and WT (-log EC50M=7.3) arteries through
      prazosin-sensitive receptors. Maximum (-)-noradrenaline-evoked contractions were
      greater in cav-1KO than WT arteries. (-)-Isoprenaline relaxed WT arteries (-log
      EC50M=7.3) more potently than cav-1KO arteries (-log EC50M=6.8); the effects were
      antagonized partially and similarly by the beta2-selective antagonist ICI118551
      (50 nM). The (-)-isoprenaline-evoked relaxation was partially antagonized by the
      beta1-adrenoceptor-selective antagonist CGP20712 (300 nM) in WT but not cav-1KO
      arteries. The beta3-adrenoceptor-selective antagonist L748337 (100 nM) partially
      antagonized the relaxant effects of (-)-isoprenaline in cav-1KO but not in WT
      arteries. BRL37344 partially relaxed arteries through beta3-adrenoceptors in cav
      1KO but not WT. The relaxant effects of BRL37344 were decreased by the NO
      synthase inhibitor OmegaL-nitroarginine. CONCLUSIONS AND IMPLICATIONS: The
      function of arterial alpha1- and beta2-adrenoceptors is similar in cav-1KO and WT
      mice. beta1-adrenoceptor-mediated relaxation in WT is lost in cav-1KO and
      replaced by the appearance of beta3-adrenoceptors.

PMID- 17179951
TI  - Omega-3 polyunsaturated fatty acids (PUFAs or fish oils) and atrial fibrillation.

PMID- 17179952
TI  - n-3 (omega-3) polyunsaturated fatty acids prevent acute atrial
      electrophysiological remodeling.
AB  - BACKGROUND AND PURPOSE: Recent reports suggest that n-3 (omega-3) polyunsaturated
      fatty acids (PUFAs) may reduce atrial fibrillation (AF). Reduction of the atrial
      effective refractory period (ERP) is believed to be an important early remodeling
      event that favors the development and perpetuation of AF. We hypothesized that n
      3 PUFAs would attenuate early atrial electrophysiolgical remodeling in a canine
      model of acute atrial tachypacing. EXPERIMENTAL APPROACH: Adult dogs of either
      sex received n-3 PUFAs (n=6), n-6 PUFAs (n=6), or saline (n=6) infused over 1 h.
      After a stable ERP was established, treatment was initiated concurrently with 6 h
      of rapid atrial pacing (400 b.p.m.). Serial right atrial ERPs were measured
      during rapid atrial pacing, and induction of atrial tachyarrhythmias was
      attempted at the conclusion of each study. KEY RESULTS: There was no change in P
      wave duration or in the PQ, QRS, QT or QTc intervals in any of the treatment
      groups. N-3 PUFA treatment significantly reduced the shortening of atrial ERP,
      compared to both control groups (P<0.05). In separate experiments, the same n-3
      PUFA infusion was given to dogs remaining in normal sinus rhythm. During sinus
      rhythm, n-3 PUFA infusion did not alter any electrocardiogram (ECG) parameter or
      the atrial ERP. CONCLUSIONS AND IMPLICATIONS: We conclude that acute n-3 PUFA
      treatment prevents acute atrial electrophysiological remodeling during high rate
      activity, which may minimize the self-perpetuation of AF.

PMID- 17179953
TI  - Characterization of kinin receptors in human cultured detrusor smooth muscle
      cells.
AB  - BACKGROUND AND PURPOSE: Kinins have an important role in inflammatory cystitis
      and in animal pathophysiological models, by acting on epithelium, fibroblasts,
      sensory innervation and smooth muscle. The aim of this study was to characterize
      the receptors responsible for direct motor responses induced by kinins on human
      detrusor. EXPERIMENTAL APPROACH: Human detrusor cells from biopsies were isolated
      and maintained in culture. B(1) and B(2) kinin receptors were characterized by
      means of radioligand and functional experiments (PI accumulation and PGE(2)
      release). KEY RESULTS: [(3)H]-[desArg(9)]-Lys-BK and [(3)H]-BK saturation studies
      indicated receptor density (B(max)) and K (d) values of 19 or 113 fmol mg(-1),
      and 0.16 or 0.11 nM for the B(1) or B(2) receptors, respectively. Inhibition
      binding studies indicated the selectivity of the B(1) receptor antagonist
      [desArg(9)Leu(8)]-Lys-BK and of the B(2) receptor antagonists Icatibant and
      MEN16132. [DesArg(9)]-Lys-BK and BK induced PI accumulation with an EC(50) of 1.6
      and 1.4 nM and different maximal responses (E(max) of [desArg(9)]-Lys-BK was 10%
      of BK). BK also induced prostaglandin E(2) release (EC(50) 2.3 nM), whereas no
      response was detected with the B(1) receptor agonist. The incubation of detrusor
      smooth muscle cells with interleukin 1beta (IL-1beta) or tumour necrosis factor
      alpha (TNF-alpha) (10 ng ml(-1)) induced a time-dependent increase in radioligand
      specific binding, which was greater for the B(1) than for the B(2) receptor.
      CONCLUSIONS AND IMPLICATIONS: Human detrusor smooth muscle cells in culture
      retain kinin receptors, and represent a suitable model to investigate the
      mechanisms and changes that occur under chronic inflammatory conditions.

PMID- 17179954
TI  - Protease-activated receptor-4: a novel mechanism of inflammatory pain modulation.
AB  - BACKGROUND AND PURPOSE: Protease-activated receptor-4 (PAR(4)), the most recently
      discovered member of the PARs family, is activated by thrombin, trypsin and
      cathepsin G, but can also be selectively activated by small synthetic peptides
      (PAR(4)-activating peptide, PAR(4)-AP). PAR(4) is considered a potent mediator of
      platelet activation and inflammation. As both PAR(1) and PAR(2) have been
      implicated in the modulation of nociceptive mechanisms, we investigated the
      expression of PAR(4) in sensory neurons and the effects of its selective
      activation on nociception. EXPERIMENTAL APPROACH AND KEY RESULTS: We demonstrated
      the expression of PAR(4) in sensory neurons isolated from rat dorsal root ganglia
      by reverse transcription-polymerase chain reaction and immunofluorescence. We
      found that PAR(4) colocalized with calcitonin gene-related peptide and substance
      P. We also showed that a selective PAR(4)-AP was able to inhibit calcium
      mobilization evoked by KCl and capsaicin in rat sensory neurons. Moreover, the
      intraplantar injection of a PAR(4)-AP significantly increased nociceptive
      threshold in response to thermal and mechanical noxious stimuli, while a PAR(4)
      inactive control peptide had no effect. The anti-nociceptive effects of the
      PAR(4)-AP were dose-dependent and occurred at doses below the threshold needed to
      cause inflammation. Finally, co-injection of the PAR(4)-AP with carrageenan
      significantly reduced the carrageenan-induced inflammatory hyperalgesia and
      allodynia, but had no effect on inflammatory parameters such as oedema and
      granulocyte infiltration. CONCLUSIONS AND IMPLICATIONS: Taken together, these
      results identified PAR(4) as a novel potential endogenous analgesic factor, which
      can modulate nociceptive responses in normal and inflammatory conditions.

PMID- 17179956
TI  - Role of p38 mitogen-activated protein kinase in cardiac remodelling.
AB  - BACKGROUND AND PURPOSE: Mitogen-activated protein kinases (MAPK) are centrally
      involved in several mechanisms important for heart failure such as apoptosis,
      activation of inflammatory responses and cell proliferation. We therefore
      evaluated the effect of the selective p38 MAPK inhibitor SB 239063 on progression
      of left ventricular remodelling after myocardial infarction (MI) in rats.
      EXPERIMENTAL APPROACH: Rats were treated for 9 weeks with placebo or SB 239063 by
      gavage (15 mg kg(-1)) twice daily starting 7 days after ligation of the left
      anterior descending artery. Serial transthoracic echocardiography was performed
      at days 7, 36 and 70. KEY RESULTS: Over the 9 weeks, mortality was not different
      between the groups. On echocardiography, animals after myocardial infarction
      exhibited significant left ventricular dilatation as expected (week 10, end
      systolic diameter, placebo sham 5.21+/- 0.34 vs. placebo MI 8.44+/- 0.57 mm).
      However, there was no difference between placebo and SB 239063-treated rats (week
      10, end-systolic diameter, SB MI 7.76+/- 0.74 mm, not significantly different
      from placebo MI). Haemodynamics changed accordingly. Moreover, SB 239063 had no
      effect on left ventricular hypertrophy. Treatment with SB 239063 significantly
      reduced cytokine expression of tumour necrosis factor and interleukin-1beta after
      myocardial infarction. However, collagen content was not influenced by the
      treatment. CONCLUSION: Despite a reduction of inflammation, treatment with the
      p38 inhibitor SB 239063 does not affect cardiac remodelling and cardiac function
      when treatment is started 7 days after myocardial infarction.

PMID- 17179957
TI  - Ultrastructural features of lymphocyte suppression induced by anthrax lethal
      toxin and treated with chloroquine.
AB  - Antibacterial therapy does not fully protect against anthrax because of severe
      systemic intoxication. Lysosomal processing of anthrax lethal toxin (LTX) is a
      key event in the disease pathogenesis, and agents interfering with this process,
      like chloroquine (CQ), may have practical applications. Although LTX is known to
      induce T-cell suppression, precise mechanisms of this phenomenon are not
      completely characterized. In the present study, we investigated alterations of
      lymphocyte ultrastructure caused by LTX and associated with favorable effect of
      CQ on the LTX-related dysfunction. Peripheral blood lymphocytes were activated
      via CD3 crosslinking in the presence or absence of LTX and CQ, and examined by
      transmission electron microscopy, flow cytometry and immunoblotting. Crosslinking
      of CD3 induced ultrastructural signs of lymphocyte activation, mostly disappeared
      after LTX treatment. The cell ultrastructure was well preserved in LTX-treated
      cells, despite dose- and time-dependent inhibition of T-cell function associated
      with impaired activation of mitogen-activated protein kinase. Regardless of
      intracellular signaling abnormalities, LTX did not decrease T-cell viability. CQ
      restored expression of CD69 (P<0.001) and improved phosphorylation of p38
      (P=0.022) in LTX-exposed T lymphocytes. The exposure of cells to CQ, with or
      without LTX, led to appearance of many phagolysosomes with heterogeneous content,
      possibly representing unprocessed internalized material. In conclusion, LTX
      suppressed T-cell functions, but did not affect the viability and caused no
      ultrastructural damage. Ultrastructural observations indicated that CQ reduced
      harmful effects of LTX, possibly by interfering with lysosomal activity.

PMID- 17179955
TI  - Role of carbon monoxide in electrically induced non-adrenergic, non-cholinergic
      relaxations in the guinea-pig isolated whole trachea.
AB  - BACKGROUND AND PURPOSE: Nitric oxide (NO) and vasoactive intestinal peptide (VIP)
      are considered transmitters of non-adrenergic, non-cholinergic (NANC) relaxations
      in guinea-pig trachea, whereas the role of carbon monoxide (CO) is unknown. This
      study was designed to assess the participation of CO, and to investigate the
      localization of haem oxygenase-2 (HO-2), the CO-producing enzyme, in tracheal
      neurons. EXPERIMENTAL APPROACH: NANC responses to electrical field stimulation
      (EFS) at 3 and 10 Hz were evaluated in epithelium-free whole tracheal segments as
      intraluminal pressure changes. Drugs used were: L-nitroarginine methyl ester (L
      NAME, 100 microM) to inhibit NO synthase (NOS), alpha-chymotrypsin (2 U ml(-1))
      to inactivate VIP, zinc protoporphyrin-IX (ZnPP-IX, 10 microM) to inhibit HO-2,
      and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM), a soluble
      guanylyl cyclase inhibitor. For immunohistochemistry, tissues were exposed to
      antibodies to PGP 9.5, a general neuronal marker, HO-2 and NOS, and processed
      with an indirect immunofluorescence method. KEY RESULTS: alpha-Chymotrypsin did
      not affect NANC relaxations. ODQ inhibited NANC responses by about 60%, a value
      similar to that obtained by combining L-NAME and ZnPP-IX. The combination of ODQ,
      L-NAME and ZnPP-IX reduced the responses by 90%. Subpopulations of HO-2 positive
      neurons containing NOS were detected in tracheal sections. CONCLUSIONS AND
      IMPLICATIONS: In the guinea-pig trachea, NANC inhibitory responses at 3 and 10 Hz
      use NO and CO as main transmitters. Their participation is revealed following
      inhibition of NOS, HO-2 and soluble guanylyl cyclase. The involvement of CO as a
      relaxing transmitter paves the way for novel therapeutic approaches in the
      treatment of airway obstruction.

PMID- 17179960
TI  - Organ-specific regulation of innate immunity.
AB  - Immune responses to microbial challenge in various tissues are not the same.
      Organ-specific immune responses are adapted to maintain organ physiology.

PMID- 17179958
TI  - Roles of coagulation pathway and factor Xa in rat mesangioproliferative
      glomerulonephritis.
AB  - Tissue factor initiates the extrinsic coagulation pathway by activating
      coagulation factor X to factor Xa, and factor V is a cofactor for the prothrombin
      activation by factor Xa. As factor Xa is known to promote the proliferation of
      mesangial cells in culture, the roles of the coagulation pathway and factor Xa
      were studied in an animal model of mesangioproliferative glomerulonephritis
      (MsPGN). MsPGN was induced in Wistar rats by an intravenous injection of anti-Thy
      1.1 monoclonal antibody, OX-7. To clarify the role of factor Xa in MsPGN, a
      specific factor Xa inhibitor, DX-9065a, was injected intravenously at 2.5 or 10
      mg/kg at the same time as OX-7, and kidney involvement was assessed by
      immunohistological analyses. We also examined p44/42 mitogen-activated protein
      (MAP) kinase activation. Time-course study revealed that expressions of tissue
      factor, factor V, and protease-activated receptor 2 (PAR2) were peaked on day 3,
      followed by factor X accumulation and mesangial proliferation. DX-9065a treatment
      significantly ameliorated proteinuria in a dose-dependent manner on day 8.
      Histological analyses showed a significant reduction in the size of glomeruli,
      the total number of glomerular cells, and crescent formation by DX-9065a
      treatment. Macrophage infiltration, which was rapidly observed on day 1 in
      disease control rats was not inhibited on days 1-3 by DX-9065a treatment, however
      it was suppressed on days 5-8. The deposition of fibrin, the number of PCNA
      positive cells, and phosphorylation of p44/42 MAP kinase were markedly increased
      in the disease control group, whereas they were significantly reduced in the
      treatment group. Tissue factor and factor V induction may accelerate MsPGN
      through the activation and accumulation of factor X via proinflammatory and
      procoagulant mechanisms, and the inhibition of factor Xa would be a promising
      method to regulate the disease process.

PMID- 17179961
TI  - Conceptualizing immune responsiveness.
AB  - Communicating about and comprehending immune responses and immunity will be
      facilitated by greater attention to semantic precision and consistency and
      increased willingness to engage with the full dimensionality and quantitative
      nature of immunological phenomena.

PMID- 17179962
TI  - On observing and analyzing disease versus signals.
AB  - The immune system has co-evolved with microbes that cause acute infectious
      disease. Immune responses must be appropriate to allow survival of both the
      individual and the species. These responses involve complex interactions that
      often go unmeasured.

PMID- 17179963
TI  - Friendly and dangerous signals: is the tissue in control?
AB  - In their own defense, tissues send a panoply of signals that initiate immunity
      and guide the choice of effector class. T(H)1-T(H)2 and T(reg) is far too simple
      a representation of the breathtaking variety of the resulting responses.

PMID- 17179964
TI  - Shigella rewrites host transcriptional responses.

PMID- 17179965
TI  - DEteCTINg fungal pathogens.

PMID- 17179966
TI  - Osteopontin-induced survival of T cells.

PMID- 17179967
TI  - Trimming creates a new self-image.

PMID- 17179969
TI  - T cell-directed therapies: lessons learned and future prospects.
AB  - Agents interfering with T cell function are therapeutic mainstays for various
      autoimmune diseases and for transplant approaches to organ failure. The
      understanding of T cell biology has blossomed since the development of most
      agents now in use. Here we discuss T cell-specific agents now in use, others
      recently added to the therapeutic armamentarium and promising agents being
      investigated in clinical and preclinical studies. In addition, we reflect on the
      risks and benefits involved in the testing of such agents clinically, with
      examples of agents that have successfully been used in the clinic and agents that
      failed to reach therapeutic use.

PMID- 17179970
TI  - Guidelines for the conduct of clinical trials for spinal cord injury as developed
      by the ICCP panel: clinical trial design.
AB  - The International Campaign for Cures of Spinal Cord Injury Paralysis established
      a panel tasked with reviewing the methodology for clinical trials for spinal cord
      injury (SCI), and making recommendations on the conduct of future trials. This is
      the fourth of four papers. Here, we examine the phases of a clinical trial
      program, the elements, types, and protocols for valid clinical trial design. The
      most rigorous and valid SCI clinical trial would be a prospective double-blind
      randomized control trial utilizing appropriate placebo control subjects. However,
      in specific situations, it is recognized that other trial procedures may have to
      be considered. We review the strengths and limitations of the various types of
      clinical trials with specific reference to SCI. It is imperative that the design
      and conduct of SCI clinical trials should meet appropriate standards of
      scientific inquiry to insure that meaningful conclusions about efficacy and
      safety can be achieved and that the interests of trial subjects are protected. We
      propose these clinical trials guidelines for use by the SCI clinical research
      community.

PMID- 17179971
TI  - Guidelines for the conduct of clinical trials for spinal cord injury as developed
      by the ICCP Panel: clinical trial inclusion/exclusion criteria and ethics.
AB  - The International Campaign for Cures of Spinal Cord Injury Paralysis established
      a panel tasked with reviewing the methodology for clinical trials for spinal cord
      injury (SCI), and making recommendations on the conduct of future trials. This is
      the third of four papers. It examines inclusion and exclusion criteria that can
      influence the design and analysis of clinical trials in SCI, together with
      confounding variables and ethical considerations. Inclusion and exclusion
      criteria for clinical trials should consider several factors. Among these are (1)
      the enrollment of subjects at appropriate stages after SCI, where there is
      supporting data from animal models or previous human studies; (2) the severity,
      level, type, or size of the cord injury, which can influence spontaneous recovery
      rate and likelihood that an experimental treatment will clinically benefit the
      subject; and (3) the confounding effects of various independent variables such as
      pre-existing or concomitant medical conditions, other medications, surgical
      interventions, and rehabilitation regimens. An issue of substantial importance in
      the design of clinical trials for SCI is the inclusion of blinded assessments and
      sham surgery controls: every effort should be made to address these major issues
      prospectively and carefully, if clear and objective information is to be gained
      from a clinical trial. The highest ethical standards must be respected in the
      performance of clinical trials, including the adequacy and clarity of informed
      consent.

PMID- 17179972
TI  - Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as
      developed by the ICCP panel: clinical trial outcome measures.
AB  - An international panel reviewed the methodology for clinical trials of spinal
      cord injury (SCI), and provided recommendations for the valid conduct of future
      trials. This is the second of four papers. It examines clinical trial end points
      that have been used previously, reviews alternative outcome tools and identifies
      unmet needs for demonstrating the efficacy of an experimental intervention after
      SCI. The panel focused on outcome measures that are relevant to clinical trials
      of experimental cell-based and pharmaceutical drug treatments. Outcome measures
      are of three main classes: (1) those that provide an anatomical or neurological
      assessment for the connectivity of the spinal cord, (2) those that categorize a
      subject's functional ability to engage in activities of daily living, and (3)
      those that measure an individual's quality of life (QoL). The American Spinal
      Injury Association impairment scale forms the standard basis for measuring
      neurologic outcomes. Various electrophysiological measures and imaging tools are
      in development, which may provide more precise information on functional changes
      following treatment and/or the therapeutic action of experimental agents. When
      compared to appropriate controls, an improved functional outcome, in response to
      an experimental treatment, is the necessary goal of a clinical trial program.
      Several new functional outcome tools are being developed for measuring an
      individual's ability to engage in activities of daily living. Such clinical end
      points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures
      often do not correlate tightly with the above outcome tools, but may need to form
      part of Phase 3 trial measures.

PMID- 17179973
TI  - Guidelines for the conduct of clinical trials for spinal cord injury as developed
      by the ICCP panel: spontaneous recovery after spinal cord injury and statistical
      power needed for therapeutic clinical trials.
AB  - The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP)
      supported an international panel tasked with reviewing the methodology for
      clinical trials in spinal cord injury (SCI), and making recommendations on the
      conduct of future trials. This is the first of four papers. Here, we examine the
      spontaneous rate of recovery after SCI and resulting consequences for achieving
      statistically significant results in clinical trials. We have reanalysed data
      from the Sygen trial to provide some of this information. Almost all people
      living with SCI show some recovery of motor function below the initial spinal
      injury level. While the spontaneous recovery of motor function in patients with
      motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI
      patients (American spinal injury Association impairment scale (AIS) C and AIS D)
      is both more substantial and highly variable. With motor complete lesions (AIS
      A/AIS B) the majority of functional return is within the zone of partial
      preservation, and may be sufficient to reclassify the injury level to a lower
      spinal level. The vast majority of recovery occurs in the first 3 months, but a
      small amount can persist for up to 18 months or longer. Some sensory recovery
      occurs after SCI, on roughly the same time course as motor recovery. Based on
      previous data of the magnitude of spontaneous recovery after SCI, as measured by
      changes in ASIA motor scores, power calculations suggest that the number of
      subjects required to achieve a significant result from a trial declines
      considerably as the start of the study is delayed after SCI. Trials of treatments
      that are most efficacious when given soon after injury will therefore, require
      larger patient numbers than trials of treatments that are effective at later time
      points. As AIS B patients show greater spontaneous recovery than AIS A patients,
      the number of AIS A patients requiring to be enrolled into a trial is lower. This
      factor will have to be balanced against the possibility that some treatments will
      be more effective in incomplete patients. Trials involving motor incomplete SCI
      patients, or trials where an accurate assessment of AIS grade cannot be made
      before the start of the trial, will require large subject numbers and/or better
      objective assessment methods.

PMID- 17179974
TI  - A demographic profile of traumatic and non-traumatic spinal injury cases: a
      hospital-based study from India.
AB  - STUDY DESIGN AND SUBJECTS: Retrospective descriptive analysis of data of patients
      with spinal injuries admitted to a tertiary referral medical center from January
      1, 2003 to December 31, 2004. OBJECTIVES: To identify the demographic profile of
      patients with spinal injuries admitted in this hospital. SETTING: Medical records
      department, Kasturba Hospital, Manipal, Karnataka, India. METHODS: A total of 207
      patients with traumatic and non-traumatic spinal injuries were included in the
      study. The patient characteristics that were included were age groups, neurologic
      status, mode and neurological level of injury, management and recovery pattern.
      RESULTS: Ratio of men to women who sustained spinal injuries was 3.6:1. The
      maximum number of patients was in the age range of 20-39 years. The different
      levels of spine that sustained injuries were cervical spine (36.2%), thoracic
      spine (34.3%) and lumbar spine (29.5%). There were 118 patients with neurological
      deficit. Mechanisms of injury recorded were fall from height (58.9%), fall of
      weight (7.2%), motor vehicle accidents (21.3%) and non-traumatic causes (12.6%).
      Of these 207 spinal injury patients, 74.4% were managed conservatively, whereas
      25.6% patients were managed surgically. OBSERVATION: This study gives a
      preliminary overview of the characteristics of patients with spinal injuries in
      this hospital.

PMID- 17179975
TI  - Proteus bacteriuria is associated with significant morbidity in spinal cord
      injury.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVES: We investigated the
      morbidity associated with Proteus bacteriuria in a spinal cord injured (SCI)
      population. SETTING: Michael E DeBakey Veterans Affairs Medical Center in
      Houston, Texas, USA. METHODS: We reviewed the medical records of all veterans
      with SCI who received care in our medical center during the past 3 years. Proteus
      bacteriuria was defined as the growth of Proteus species in any urine culture
      during the study period. Urinary stones were defined as either renal or bladder
      calculi. RESULTS: During the study period, 71 of the 501 subjects (14%) had
      Proteus and 90 (18%) had urinary stones. Twenty-seven percent of the subjects
      with Proteus had stones, and the association of Proteus with stones was
      significant (P<0.05). Proteus bacteriuria was likewise associated with complete
      injury, hospitalization, decubitus ulcers, and history of stones (P<0.001).
      Subjects using indwelling catheters, either transurethral or suprapubic, were
      significantly more likely to have Proteus, whereas subjects practising
      spontaneous voiding and clean intermittent catheterization were significantly
      less likely to have Proteus. In the 90 patients with stones, Proteus was
      associated with requiring treatment for stones and having multiple stones
      (P<0.01). Twenty-five of the 90 patients with stones (28%) required treatment,
      most often with lithotripsy, and 6 (7%) developed urosepsis. CONCLUSIONS: In
      persons with SCI, Proteus was found in subjects with a greater degree of
      impairment who were more likely to be hospitalized, to have decubiti, and to use
      indwelling catheters. Bacteriuria with Proteus predicted urologic complications
      in persons with SCI. STATEMENT OF ETHICS: All applicable institutional and
      governmental regulations concerning the ethical use of human volunteers were
      followed during the course of this research.

PMID- 17179976
TI  - Condition-related coping strategies in persons with spinal cord lesion: a cross
      national validation of the Spinal Cord Lesion-related Coping Strategies
      Questionnaire in four community samples.
AB  - STUDY DESIGN: Cross-sectional, questionnaire. OBJECTIVES: Coping strategies
      employed to manage the consequences of a spinal cord lesion (SCL) have been found
      to be distinctly related to emotional well-being. However, research and clinical
      implications have been hampered by the lack of cross-validated measures that are
      directly related to the lesion and its consequences. This study investigates the
      psychometric performance of the SCL-related Coping Strategies Questionnaire in
      four different countries. SETTING: Austria, Germany, Switzerland and UK. METHODS:
      The study sample comprised 355 community residing persons with SCL. Multi
      trait/multi-item analysis methods and non-parametric and parametric tests were
      used. RESULTS: The Acceptance coping scale showed satisfactory psychometric
      qualities, whereas there were some problems in the Fighting spirit scale and
      greater problems in the Social reliance scale. Compared with the Swedish
      developmental sample, Acceptance was used more in the four study countries.
      Consistent with the original sample, Acceptance and Fighting spirit coping
      correlated with fewer signs of emotional distress, persons lesioned > or = 5
      years tended to report more Acceptance than the newly lesioned and coping
      strategies were mainly unrelated to neurological status. CONCLUSION: The English
      and German language versions of the Acceptance coping scale were valid and
      reliable, whereas some translated items in the Fighting spirit scale need to be
      revised. Translations of the Social reliance scale need to be thoroughly revised
      and retested. The results add further evidence to the literature on the stability
      of the link between adapting life priorities (ie Acceptance) and emotional well
      being.

PMID- 17179977
TI  - Acute spinal cord injury changes the disposition of some, but not all drugs given
      intravenously.
AB  - STUDY DESIGN: Experimental laboratory investigations in paraplegic rats.
      OBJECTIVE: In order to understand why acute spinal cord injury (SCI) changes the
      disposition of some, but not all drugs given intravenously (i.v.),
      pharmacokinetic parameters of drugs with different pharmacological properties
      were evaluated to determine the influence of SCI on physiological processes such
      as distribution, metabolism and excretion. SETTING: Mexico City, Mexico. METHODS:
      Rats were subjected to severe SCI (contusion) at T-9 level; pharmacokinetic
      studies of phenacetin, naproxen or gentamicin were performed 24 h after. These
      drugs were not chosen as markers because of their therapeutic properties, but
      because of their pharmacokinetic characteristics. Additional studies including
      plasma proteins, liver and renal function tests, and micro-vascular hepatic blood
      flow, were also performed at the same time after injury. RESULTS: Acute SCI
      significantly reduced distribution of drugs with intermediate and low binding to
      plasma proteins (phenacetin 30% and gentamicin 10%, respectively), but
      distribution did not change when naproxen - a drug highly bound to plasma
      proteins (99%) - was used, in absence of changes in plasma proteins. Metabolism
      was significantly altered only for a drug with liver blood flow - limited
      clearance (phenacetin) and not for a drug with liver capacity-limited clearance
      (naproxen). The liver function test did not change, whereas the hepatic micro
      vascular blood flow significantly decreased after SCI. Renal excretion, evaluated
      by gentamicin clearance, was significantly reduced as a consequence of SCI,
      without significant changes in serum creatinine. CONCLUSIONS: Changes in drug
      disposition associated to acute SCI are complex and generalization is not
      possible. They are highly dependent on each drug properties as well as on the
      altered physiological processes. Results motivate the quest for strategies to
      improve disposition of selective i.v. drugs during spinal shock, in an effort to
      avoid therapeutic failure.

PMID- 17179978
TI  - Apical soft tissue biopsies predict biochemical failure in radical perineal
      prostatectomy patients with apical cancer involvement.
AB  - The aim of the study was to prospectively assess the role of apical soft tissue
      biopsies in radical perineal prostatectomy (RPP) patients with documented apical
      prostate cancer (PCA) involvement. Between June 1998 and May 1999, 77 consecutive
      men with localized PCA and documented invasion of the prostatic apex underwent
      RPP by a single surgeon. Soft tissue biopsies were systematically obtained from
      the prostatic fossa overlying the apex at the time of surgery. Time to
      biochemical failure was calculated using the Kaplan-Meier method. The rates of
      positive apical margins and positive apical soft tissue biopsies were 23.4%
      (18/77) and 15.6% (12/77). The sensitivity, specificity and positive predictive
      value of positive apical margins for residual apical disease as determined by
      apical soft tissue biopsy were 41.7, 80, and 28%, respectively. The overall
      biochemical failure rate was 28.6% (22/77) with a median follow-up of 51 months
      (range 3-73 months). The 36-month biochemical recurrence-free survival rate was
      55.9+/-14.9% for patients with positive apical biopsies and 78.7+/-5.3% for those
      with negative biopsies (P=0.023). In conclusion, positive apical soft tissue
      biopsy is an independent predictor of biochemical failure in patients with apical
      PCA who undergo RPP. Positive apical surgical margins poorly predict residual
      apical disease that is frequently identifiable by apical soft tissue biopsy.
      Apical soft tissue biopsies should therefore be obtained in patients with known
      extensive apical cancer involvement at the time of RPP.

PMID- 17179979
TI  - The association between body size, prostate volume and prostate-specific antigen.
AB  - Increasing prostate volume contributes to urinary tract symptoms and may obscure
      prostate cancer detection. We investigated the association between obesity and
      prostate volume, prostate-specific antigen (PSA) and PSA density among 753 men
      referred for prostate biopsy. Among men with a negative biopsy, prostate volume
      significantly increased approximately 25% from the lowest to highest body mass
      index (BMI), waist or hip circumference or height categories. PSA was 0.7 ng/ml
      lower with a high waist-to-hip ratio. These associations were less consistent
      among subjects diagnosed with high-grade prostatic intraepithelial neoplasia or
      cancer. Our data suggest that obesity and height are independently associated
      with prostate volume..

PMID- 17179980
TI  - Functional analysis of a cotton glucuronosyltransferase promoter in transgenic
      tobaccos.
AB  - The 5' fragment (1 647 bp) of the cotton glucuronosyltransferase gene (GhGlcAT1)
      was transcriptionally fused to the beta-glucuronidase (GUS) gene, and
      functionally analyzed for important regulatory regions controlling gene
      expression in transgenic tobacco plants. GUS activity analysis revealed that the
      full-length promoter drives efficient expression of the GUS gene in the root cap,
      seed coat, pollen grains and trichomes. Exposure of the transgenic tobacco to
      various abiotic stresses showed that the promoter was mainly responsive to the
      sugars (glucose and sucrose) as well as gibberellic acid. Progressive upstream
      deletion analyses of the promoter showed that the region from -281 to +30 bp is
      sufficient to drive strong GUS expression in the trichomes of shoot, suggesting
      that the 311 bp region contains all cis-elements needed for trichome-specific
      expression. Furthermore, deletion analysis also revealed that the essential cis
      element(s) for sucrose induction might be located between -635 and -281 bp. In
      addition, sequence analysis of the regulatory region indicated several conserved
      motifs among which some were shared with previously reported seed-specific
      elements and sugar-responsive elements, while others were related with trichome
      expression. These findings indicate that a 1 647-bp fragment of the cotton
      GhGlcAT1 promoter contains specific transcription regulatory elements, and
      provide clues about the roles of GhGlcAT1 in cotton fiber development. Further
      analyses of these elements will help to elucidate the molecular mechanisms
      regulating the expression of the GhGlcAT1 gene during fiber elongation.

PMID- 17179981
TI  - Beyond tumorigenesis: cancer stem cells in metastasis.
AB  - The importance of cancer stem cells (CSCs) in tumor-initiation has been firmly
      established in leukemia and recently reported for a variety of solid tumors.
      However, the role of CSCs in multistage cancer progression, particularly with
      respect to metastasis, has not been well-defined. Cancer metastasis requires the
      seeding and successful colonization of specialized CSCs at distant organs. The
      biology of normal stem cells and CSCs share remarkable similarities and may have
      important implications when applied to the study of cancer metastasis.
      Furthermore, overlapping sets of molecules and pathways have recently been
      identified to regulate both stem cell migration and cancer metastasis. These
      molecules constitute a complex network of cellular interactions that facilitate
      both the initiation of the pre-metastasis niche by the primary tumor and the
      formation of a nurturing organ microenvironment for migrating CSCs. In this
      review, we surveyed the recent advances in this dynamic field and propose a
      unified model of cancer progression in which CSCs assume a central role in both
      tumorigenesis and metastasis. Better understanding of CSCs as a fundamental
      component of the metastatic cascade will lead to novel therapeutic strategies
      against metastatic cancer.

PMID- 17179982
TI  - Assessment of microsatellite instability status for the prediction of
      metachronous recurrence after initial endoscopic submucosal dissection for early
      gastric cancer.
AB  - The technique of endoscopic submucosal dissection (ESD) has been developed for en
      bloc resection of early gastric cancer (EGC); however, little is known about the
      risk of metachronous cancer in the remnant stomach after initial ESD. In this
      study, we investigated the correlation between microsatellite instability (MSI)
      status and the incidence of metachronous recurrence of gastric cancer. According
      to the genetic/molecular background determined with MSI status and expression
      levels of hMLH1 and p53 tumour suppressor, 110 EGCs removed with ESD were
      subclassified into three groups: the mutator/MSI-type (8%), suppressor/p53-type
      (45%) and unclassified type (47%). Interestingly, patients with the mutator/MSI
      type tumour had a high incidence (67%) of metachronous recurrence of gastric
      cancer within a 3-year observation after initial ESD, which was significantly
      higher than those with the suppressor/p53-type and unclassified type tumours
      (P<0.01). Although we investigated mucin phenotypes, there was no correlation
      between mucin phenotype and the recurrence of EGC. These findings suggest that
      subclassification of molecular pathological pathways in EGCs is required for the
      assessment of patients with a high risk of recurrent gastric cancer. The
      information delivered from our investigation is expected to be of value for
      decisions about therapy and surveillance after ESD.

PMID- 17179983
TI  - Elevated Bmi-1 expression is associated with dysplastic cell transformation
      during oral carcinogenesis and is required for cancer cell replication and
      survival.
AB  - Bmi-1 is a polycomb group protein that was identified as c-myc cooperating
      oncogene in murine lymphomagenesis. The current study was undertaken to determine
      the role of Bmi-1 in human oral carcinogenesis. Bmi-1 protein and RNA expression
      levels were markedly enhanced in the cells of oral squamous cell carcinomas
      (OSCC) compared with that of normal human oral keratinocytes (NHOK). Enhanced-Bmi
      1 expression was also detected in situ in the archived oral mucosal tissues with
      cancerous and precancerous histopathology, including that of mild epithelial
      dysplasia. Thus, Bmi-1 expression occurs at a very early stage in oral
      carcinogenesis. To determine the biological role of Bmi-1 in cell proliferation,
      endogenous Bmi-1 was knocked down in actively proliferating SCC4 cells and NHOK
      by RNA interference. After Bmi-1 knockdown, cell replication was severely
      retarded. However, the expression of p16(INK4A), a known cellular target of Bmi
      1, was not changed in cells with or without Bmi-1 knockdown. Furthermore, Bmi-1
      knockdown in HOK-16B-BaP-T cells, in which the p16(INK4A)/pRb pathway was
      abrogated, led to immediate arrest of replication and loss of viable cells. Thus,
      our data suggest that Bmi-1 may act through p16(INK4A)-independent pathways to
      regulate cellular proliferation during oral cancer progression.

PMID- 17179984
TI  - A prospective study of postmenopausal hormone use and ovarian cancer risk.
AB  - The relationship between postmenopausal hormone use (PMH) and ovarian cancer risk
      is unclear, particularly for specific hormone formulations, but recent studies
      suggest that there is a positive association. We conducted a prospective
      observational study with 82,905 postmenopausal women, including 389 ovarian
      cancers, in the Nurses' Health Study from 1976 to 2002. Compared with never users
      of PMH, both current and past users of > or =5 years had a significantly elevated
      risk of ovarian cancer (RR=1.41, 95% confidence interval (CI) 1.07-1.86 and
      relative risk (RR)=1.52, 95% CI 1.01-2.27, respectively). Examined by hormone
      type in continuous years, use of unopposed estrogen was associated with a
      significant increase in the risk of epithelial ovarian cancer (P for trend
      <0.001; RR for 5-year increment of use=1.25, 95% CI 1.12-1.38). Use of estrogen
      plus progestin (RR for 5-year increment of use=1.04, 95% CI 0.82-1.32) was not
      significantly associated with ovarian cancer risk. Generally, results were
      similar for serous tumours (RR for 5-year increment of unopposed estrogen
      use=1.23, 95% CI 1.07-1.40) and slightly stronger for endometrioid tumours (RR
      for 5-year increment of unopposed estrogen use=1.53, 95% CI 1.20-1.94). Recency
      of use was not significantly associated with ovarian cancer risk, but statistical
      power was limited here.

PMID- 17179985
TI  - Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence
      and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.
AB  - Hypoxia-inducible factor-1 (HIF-1)alpha expression was studied in the gastric
      carcinogenesis sequence and as a prognostic factor in surgically resected gastric
      and gastro-oesophageal junction tumours. Protein expression was examined using
      immunohistochemistry on formalin-fixed biopsies of normal mucosa (n=20),
      Helicobacter pylori associated gastritis (n=24), intestinal metaplasia (n=24),
      dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. The
      relationship between HIF-1alpha expression and prognosis was assessed in
      resection specimens from 177 patients with gastric and gastro-oesophageal
      junction adenocarcinoma. Hypoxia-inducible factor-1alpha expression was not
      observed in normal gastric mucosa but increased in density (P<0.01) and intensity
      (P<0.01) with progression from H. pylori-associated gastritis, intestinal
      metaplasia, dysplasia to adenocarcinoma. The pattern of staining in the resection
      specimens was focally positive in 49 (28%) and at the invasive tumour edge in 41
      (23%). Invasive edge expression was associated with lymph node metastases
      (P=0.034), advanced TNM stage (P=0.001) and was an adverse prognostic factor for
      cancer-specific survival (P=0.019). In univariate analysis and in comparison with
      tumours not expressing HIF-1alpha, invasive edge staining was associated with a
      hazard ratio of 1.6 (95% CI 1.0-2.5) and focally positive staining a hazard ratio
      of 0.7 (95% CI 0.5-1.2). Hypoxia-inducible factor-1alpha lost prognostic
      significance in multivariate analysis. The results suggest HIF-1alpha is involved
      in gastric carcinogenesis and disease progression, but is only a weak prognostic
      factor for survival.

PMID- 17179986
TI  - Wait times for breast cancer care.
AB  - Measurement of care time intervals is complex, being influenced by many factors.
      The definition of the care interval monitored can also bias the detection of
      changes in waits. The implications of using different care interval definitions
      to report wait times and identify delays in care provision were examined using a
      retrospective chart review of 637 women with surgically treated breast cancer who
      were referred to a cancer centre between September 1999 and 2000 or September
      2003 and 2004. Overall waits between detection and adjuvant treatment increased
      by 12 days over the two periods, but their exact location and cause(s) could not
      be determined at such a low-resolution interval. At higher resolutions of care
      intervals, reporting the comprehensive sequence of care events, the prolongation
      was mainly associated with delayed access to surgery (4 days) and delivery of
      adjuvant chemotherapy (4 days). The latter went unnoticed when waits were
      reported at intermediate (referral to adjuvant treatment) and low (detection to
      adjuvant treatment) resolutions. Disease stage and type of first adjuvant
      treatment consistently and significantly influenced the length of waits.
      Comprehensive monitoring of the entire care path is essential to effectively
      prioritize interventions, assess their outcomes and optimise access to cancer
      care.

PMID- 17179987
TI  - Targeting BRAF in thyroid cancer.
AB  - Activating mutations in the gene encoding BRAF are the most commonly identified
      oncogenic abnormalities in papillary thyroid cancer. In vitro and in vivo models
      have demonstrated that overexpression of activated BRAF induces malignant
      transformation and aggressive tumour behaviour. BRAF and other RAF kinases are
      frequently activated by other thyroid oncogenes and are important mediators of
      their biological effects including dedifferentiation and proliferation. Because
      current therapeutic options for patients with thyroid cancers that are aggressive
      and/or do not respond to standard therapies are limited, BRAF and its downstream
      effectors represent attractive therapeutic targets. In this review, data
      supporting a role for BRAF activation in thyroid cancer development and
      establishing the potential therapeutic efficacy of BRAF-targeted agents in
      patients with thyroid cancer will be reviewed.

PMID- 17179988
TI  - Stem cells of ependymoma.
AB  - Ependymomas are tumours that arise throughout the central nervous system. Little
      is known regarding the aberrant cellular and molecular processes that generate
      these tumours. This lack of knowledge has hampered efforts to reduce the
      significant mortality and morbidity that are associated with ependymoma. Here, we
      review recent data that suggest that radial glia are cells of origin of
      ependymoma, and discuss the processes that might transform these neural
      progenitors into ependymoma cancer stem cells.

PMID- 17179989
TI  - The potential role of podoplanin in tumour invasion.
AB  - Podoplanin is a small mucin-like transmembrane protein, widely expressed in
      various specialised cell types throughout the body. Here, we revisit the
      mechanism of podoplanin-mediated tumour invasion. We compare molecular pathways
      leading to single and collective cell invasion and discuss novel distinct
      concepts of tumour cell invasion.

PMID- 17179990
TI  - Helicobacter pylori and oesophageal and gastric cancers in a prospective study in
      China.
AB  - In a cohort of 29,584 residents of Linxian, China, followed from 1985 to 2001, we
      conducted a case-cohort study of the magnitude of the association of Helicobacter
      pylori seropositivity with cancer risk in a random sample of 300 oesophageal
      squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed
      gastric non-cardia adenocarcinomas, and a random sample of the entire cohort
      (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA
      H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric
      cardia and non-cardia cancers were increased in individuals exposed to H. pylori
      (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26-2.14, and 1.60; 1.15
      2.21, respectively), whereas risk of oesophageal squamous cell cancer was not
      affected (1.17; 0.88-1.57). For both cardia and non-cardia cancers, HRs were
      higher in younger individuals. With longer time between serum collection to
      cancer diagnosis, associations became stronger for cardia cancers but weaker for
      non-cardia cancers. CagA positivity did not modify these associations. The
      associations between H. pylori exposure and gastric cardia and non-cardia
      adenocarcinoma development were equally strong, in contrast to Western countries,
      perhaps due to the absence of Barrett's oesophagus and oesophageal
      adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather
      than a mixture of gastric and oesophageal malignancies.

PMID- 17179991
TI  - Host epigenetic modifications by oncogenic viruses.
AB  - Epigenetic alterations represent an important step in the initiation and
      progression of most human cancers, but it is difficult to differentiate the early
      cancer causing alterations from later consequences. Oncogenic viruses can induce
      transformation via expression of only a small number of viral genes. Therefore,
      the mechanisms by which oncogenic viruses cause cancer may provide clues as to
      which epigenetic alterations are critical in early carcinogenesis.

PMID- 17179992
TI  - A phase I trial of the selective oral cyclin-dependent kinase inhibitor
      seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21
      days.
AB  - Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable
      inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial.
      Preclinical studies showed antitumour activity in a broad range of human tumour
      xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule.
      Twenty-one patients (median age 62 years, range: 39-73 years) were treated with
      doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg
      b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4
      hypokalaemia. Other toxicities included reversible raised creatinine (grade 2),
      reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion
      was investigated further in 12 patients, three of whom had MAG3 renograms. One
      patient with a rapid increase in creatinine on day 3 had a reversible fall in
      renal perfusion, with full recovery by day 14, and no changes suggestive of renal
      tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib
      reached peak plasma concentrations between 1 and 4 h and elimination half-life
      was 2-5 h. Inhibition of retinoblastoma protein phosphorylation was not
      demonstrated in peripheral blood mononuclear cells. No objective tumour responses
      were noted, but disease stabilisation was recorded in eight patients; this lasted
      for a total of six courses (18 weeks) in a patient with ovarian cancer.

PMID- 17179993
TI  - The Hollow Fibre Assay as a model for in vivo pharmacodynamics of
      fluoropyrimidines in colon cancer cells.
AB  - The Hollow Fibre Assay (HFA) is usually applied as an early in vivo model for
      anti-cancer drug screening, but is potentially an excellent model for short-term
      in vivo pharmacodynamic studies. We used the model to study the in vivo role of
      thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD
      ECGF) in the cytotoxicity and pharmacodynamics of TAS-102 in colon cancer cells.
      TAS-102 is a new oral drug formulation, which is composed of trifluorothymidine
      (TFT) and thymidine phosphorylase inhibitor (TPI), which prevents TFT
      degradation. We compared the activity with Xeloda (capecitabine), which is
      activated by TP into 5FU. Hollow fibres filled with human Colo320 or Colo320TP1
      colorectal cancer cells with deficient or high TP expression, respectively, were
      implanted subcutaneously (s.c.) at both flanks of BALB/c mice. The mice were
      treated orally over 5 days with TAS-102, TFT alone, 5'DFUR+/-TPI or capecitabine
      at their maximum tolerated dose (MTD). The cells were retrieved from the fibres
      and assayed for growth (MTT assay), cell cycle distribution (flow cytometry) and
      apoptosis induction (FragEL method). TAS-102 induced considerable growth
      inhibition (50%, P<0.01) to both cell lines, which was completely abolished in
      the absence of TPI. Capecitabine and its metabolite 5'DFUR reduced proliferation
      of Colo320TP1 cells in the fibres significantly (down to 25-40%), but much less
      in Colo320 cells, whereas addition of TPI reduced the effect of 5'DFUR, although
      not completely. These differences in cytotoxic effects were reflected in the
      pharmacodynamic evaluation. TAS-102 induced a G2M-phase arrest (from 25 to 40%)
      and apoptosis (>8-fold), which was more pronounced in Colo320 than in Colo320TP1.
      Again, omission of TPI neutralised the effect of TAS-102. Similarly, 5'DFUR and
      capecitabine induced a significant G2M-phase arrest (up to 45%) in the Colo320TP1
      cell line, but less pronounced in the parental Colo320. Addition of TPI to 5'DFUR
      reduced this effect to control levels. Also induction of apoptosis was reduced in
      the presence of TPI. The data demonstrated that the HFA is excellently suited for
      studying short-term pharmacodynamic effects of fluoropyrimidines in vivo. TAS-102
      is only effective in inducing cytotoxicity when systemic TPI is present, but acts
      against both low and high TP expressing colon cancer cells, while 5'DFUR needs
      cellular TP to exert significant activity.

PMID- 17179994
TI  - Beyond mammography screening: quality assurance in breast cancer diagnosis (The
      QuaMaDi Project).
AB  - As many breast cancer cases are detected outside mammographic screening, a
      multidisciplinary quality management (QuaMaDi) project involving gynaecologists,
      double reading by radiologists. and centralised assessment, documentation,
      evaluation and feedback was implemented into routine breast cancer diagnosis in
      part of Schleswig-Holstein (Germany) with a population of 365,000 women. A cohort
      of 59,514 patients eligible for diagnostic mammography was examined from May 2001
      to December 2005 and quality indicators, breast cancer incidence and tumour stage
      distribution were analysed. A total of 102,744 diagnostic processes were
      initiated, for 23.8% of which (24,470) a third expert reading at the reference
      centre was performed. Further assessment was recommended for 6.3% (6442) of all
      patients. In total, 1056 breast cancer cases were diagnosed (10.3 per 1000
      examinations). Patients of the QuaMaDi project had a higher proportion of 'in
      situ' and T1 tumours (62.6% vs Schleswig-Holstein: 48.6%), showing that the
      implementation of high standards in routine diagnostic mammography can improve
      the quality of breast cancer diagnosis and care.

PMID- 17179995
TI  - Fine mapping of the MAPT locus using quantitative trait analysis identifies
      possible causal variants in Alzheimer's disease.
AB  - In addition to senile plaques, neurofibrillary tangles are characteristic of
      Alzheimer's disease (AD) pathology, suggesting a clear involvement of the
      microtubule-associated protein tau (MAPT) in AD. Recent findings, suggesting that
      the H1c haplotype is associated with increased risk, now also implicate MAPT
      genetically. In this study, we aim to clarify this association by a fine mapping
      approach using both a traditional phenotypic association analysis and a
      quantitative trait (QT) analysis using cerebrospinal fluid (CSF) tau protein
      levels in the German population. Here, we report that both methodologies identify
      that the H1c haplotype may play important role in AD (AD risk, P=0.007,
      uncorrected; CSF tau levels, P=0.027, uncorrected). Further, the use of a sliding
      window approach in the QT analysis allowed for the narrowing down of the region
      where a probable causal variant may be located. The data suggest that this may
      lie at or within close proximity to the rs242557 single nucleotide polymorphism
      as association with CSF tau levels seems to be primarily driven by rs242557 in a
      gene dosage-dependent manner (trend model: P=0.002, uncorrected). These findings
      provide functional evidence to support the genetic association of MAPT with AD.

PMID- 17179996
TI  - Linkage and association studies in African- and Caucasian-American populations
      demonstrate that SHC3 is a novel susceptibility locus for nicotine dependence.
AB  - Our previous linkage study demonstrated that the 9q22-q23 chromosome region
      showed a 'suggestive' linkage to nicotine dependence (ND) in the Framingham Heart
      Study population. In this study, we provide further evidence for the linkage of
      this region to ND in an independent sample. Within this region, the gene encoding
      Src homology 2 domain-containing transforming protein C3 (SHC3) represents a
      plausible candidate for association with ND, assessed by smoking quantity (SQ),
      the Heaviness of Smoking Index (HSI) and the Fagerstrom Test for ND (FTND). We
      utilized 11 single-nucleotide polymorphisms within SHC3 to examine the
      association with ND in 602 nuclear families of either African-American (AA) or
      European-American (EA) origin. Individual SNP-based analysis indicated three SNPs
      for AAs and one for EAs were significantly associated with at least one ND
      measure. Haplotype analysis revealed that the haplotypes A-C-T-A-T-A of rs12519
      rs3750399-rs4877042-rs2297313-rs1547696-rs1331188, with a frequency of 27.8 and
      17.6%, and C-T-A-G-T of rs3750399-rs4877042-rs2297313-rs3818668-rs1547696, at a
      frequency of 44.7 and 30.6% in the AA and Combined samples, respectively, were
      significantly inversely associated with the ND measures. In the EA sample,
      another haplotype with a frequency of 10.6%, A-G-T-G of rs1331188-rs1556384
      rs4534195-rs1411836, showed a significant inverse association with ND measures.
      These associations remained significant after Bonferroni correction. We further
      demonstrated the SHC3 contributed 40.1-59.2% (depending on the ND measures) of
      the linkage signals detected on chromosome 9. As further support, we found that
      nicotine administered through infusion increased the Shc3 mRNA level by 60% in
      the rat striatum, and decreased it by 22% in the nucleus accumbens (NA). At the
      protein level, Shc3 was decreased by 38.0% in the NA and showed no change in the
      striatum. Together, these findings strongly implicate SHC3 in the etiology of ND,
      which represents an important biological candidate for further investigation.

PMID- 17179999
TI  - DNA fragmentation.

PMID- 17179997
TI  - Interleukin 3 and schizophrenia: the impact of sex and family history.
AB  - Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia.
      In this paper, we report evidence that multiple single nucleotide polymorphisms
      in and around interleukin 3 (IL3) are associated with the disease in the Irish
      Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control
      Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO).
      The associations are sex-specific and depend on the family history (FH) of
      schizophrenia. In all three samples, rs31400 shows female-specific and FH
      dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and
      ITRIO, respectively). Several markers have similar associations in one or two of
      the three samples. In haplotype analyses, identical risk and protective
      haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker
      combinations. For ICCSS, the same haplotypes are implicated; however, the risk
      haplotypes observed in the family samples become protective. Several significant
      markers, rs440970, rs31400 and rs2069803, are located in and around known
      estrogen response elements, promoter and enhancer of the IL3 gene. They may
      explain the sex-specific associations and be functional for the expression of IL3
      gene.

PMID- 17180000
TI  - About the involvement of deoxyribonuclease I in apoptosis.
AB  - Cell death by apoptosis is involved in a large variety of developmental events
      and physiological processes requiring a reduction in cell count. Nuclear
      collapse, one of the first visible changes denoting irreversible commitment to
      cell death by apoptosis, is frequently accompanied by chromatin degradation into
      nucleosome-sized fragments of multiples thereof. The identity of the endonuclease
      responsible for this DNA digestion has attracted some interest in recent years
      and several candidate endonucleases have been proposed. The scope of this article
      is to summarise the present knowledge about deoxyribonuclease I, one of the
      candidate enzymes.

PMID- 17180001
TI  - Deoxyribonuclease II in apoptosis and the significance of intracellular
      acidification.
AB  - Many endonucleases have been identified in cells, but which are involved in
      apoptosis remains controversial. We detected and characterized an endonuclease as
      deoxyribonuclease II. Its most important characteristic is its acidic pH optimum
      that requires decreased intracellular pH for activation. Intracellular
      acidification has been observed during apoptosis in a number of systems. This
      acidification results from a selective loss of pH regulation, and is likely due
      to dephosphorylation of proton exchangers. The fact that growth factors normally
      prevent apoptosis and also phosphorylate ion exchangers suggests the critical
      role of intracellular kinase cascades for preventing apoptosis.

PMID- 17179998
TI  - Dissecting the locus heterogeneity of autism: significant linkage to chromosome
      12q14.
AB  - Autism is a common neurodevelopmental disorder with a significant genetic
      component and locus heterogeneity. To date, 12 microsatellite genome screens have
      been performed using various data sets of sib-pair families (parents and affected
      children) resulting in numerous regions of potential linkage across the genome.
      However, no universal region or consistent candidate gene from these regions has
      emerged. The use of large, extended pedigrees is a recognized powerful approach
      to identify significant linkage results, as these families potentially contain
      more potential linkage information than sib-pair families. A genome-wide linkage
      analysis was performed on 26 extended autism families (65 affected, 184 total
      individuals). Each family had two to four affected individuals comprised of
      either avuncular or cousin pairs. For analysis, we used a high-density single
      nucleotide polymorphism genotyping assay, the Affymetrix GeneChip Human Mapping
      10K array. Two-point analysis gave peak heterogeneity limit of detection (HLOD)
      of 2.82 at rs2877739 on chromosome 14q. Suggestive linkage evidence (HLOD>2) from
      a two-point analysis was also found on chromosomes 1q, 2q, 5q, 6p,11q and 12q.
      Chromosome 12q was the only region showing significant linkage evidence by
      multipoint analysis with a peak HLOD=3.02 at rs1445442. In addition, this linkage
      evidence was enhanced significantly in the families with only male affected
      (multipoint HLOD=4.51), suggesting a significant gender-specific effect in the
      etiology of autism. Chromosome-wide haplotype analyses on chromosome 12 localized
      the potential autism gene to a 4 cM region shared among the affected individuals
      across linked families. This novel linkage peak on chromosome 12q further
      supports the hypothesis of substantial locus heterogeneity in autism.

PMID- 17180002
TI  - Apoptotic DNA degradation: evidence for novel enzymes.
AB  - Apoptosis is characterized by multiple morphological and biochemical changes. One
      biochemical change that has been primarily associated with apoptosis is the
      cleavage of chromatin in the internucleosomal regions. We have taken two
      independent approaches to investigating the enzyme(s) responsible for such
      cleavage. First, using SDS-PAGE gels with (32)P-labelled DNA incorporated into
      the matrix, we identified a nuclease activity (termed NUC18) from apoptotic
      thymocytes. This enzyme has been purified to homogeneity and the activity of the
      pure protein is dependent on Ca(2+) and Mg(2+) while inhibited by Zn(2+) and
      aurintricarboxylic acid. This protein is found in the nucleus of apoptotic and
      nonapoptotic cells but is maintained in nondying cells in a large-molecular
      weight inactive complex. NUC18 has a denatured molecular weight of 18 Kd but
      elutes from gel filtration columns with a native molecular weight of
      approximately 25 Kd. Although an exhaustive search has not been performed, NUC18
      has been identified in several cell lines and tissues. Our second approach is
      designed specifically to detect internucleosomal cleavage of DNA, an obvious
      requirement for an apoptotic nuclease. By examining the degradation of HeLa
      chromatin, we have identified a low-molecular-weight of approximately 23 Kd
      native molecular weight) internucleosomal cleavage enzyme active in nuclear
      extracts from glucocorticoid-treated thymocytes. This activity is also dependent
      upon Ca(2+)and Mg(2+) and is inhibited by Zn(2+) as well as aurintricarboxylic
      acid. It is present in a variety of cell lines and tissues and is maintained in
      control cells in a latent state prior to apoptosis. In addition to similarities
      in physical properties, the two enzymes appear to be immunologically related to
      one another by virtue of their ability to interact with the same antibody.
      Overall, using independent approaches, we have identified two nucleases with
      similar biochemical properties whose activity correlates with apoptosis. The
      current work suggests that these are novel and perhaps closely related enzymes.

PMID- 17180003
TI  - Apoptosis: the skin from a new perspective.
AB  - In this review we present skin biology from the perspective of apoptosis. We
      stress that apoptosis acts as an important homeostatic and defence mechanism in
      the developing and mature epidermis. Programmed cell death functions in
      establishing the architecture of the human epidermis and its appendages during
      development by deletion of stage-specific cells and in the adult epidermis by
      elimination of excess and abnormal cells. Arguments are presented to support the
      hypothesis that known regulators of keratinocyte growth may act as survival
      factors which suppress the cell death pathway. Surviving cells continue to divide
      until they encounter anti-proliferative factors. Then, unless cells are severely
      injured and die of necrosis, they will terminally differentiate to death or will
      die by apoptosis. The mechanisms controlling keratinocyte maturation are co
      ordinated with cell position within the epidermal strata. Inappropriate
      regulatory signals or response of a cell inappropriate to its state will activate
      apoptosis. Parallels between terminally differentiating keratinocytes and
      apoptotic cells imply that terminal differentiation and apoptosis proceed along
      the same death pathway. For terminally differentiating cells, however, this
      pathway is more elaborate because it allows expression of tissue- and
      differentiation-specific genes. A model is presented that integrates apoptosis
      and keratinocyte growth and differentiation.

PMID- 17180004
TI  - Signal antonymy: a mechanism for apoptosis induction.
AB  - The unfolding of the developmental programme and the organization of
      multicellular organisms require that cell numbers in differentiating and
      differentiated tissues are regulated. This is done by two distinct processes :
      control of cell proliferation and differentiation to a post-mitotic stage; and
      control of survival in post-mitotic cells. It is argued that elimination of cells
      by programmed cell death (PCD), which operates in both cases, is regulated by
      distinct mechanisms: PCD in post-mitotic cells corresponds to 'death-by-default'
      of (counter apoptotic) survival signals (Raff, 1992), while apoptosis in cycling
      cells, or in resting cells submitted to proliferative signals, results from
      antonymy in signalling pathways, i.e. a situation where a cell simultaneously
      engages into incompatible pathways of proliferation and cell cycle arrest.
      Antonymy arises in cells irreversibly committed to either proliferation or arrest
      and responding to a contradictory signal. In turn, the irreversible commitment
      arises by uncoupling of signal transduction from co-ordinated pathways (as in
      transformed cells with constitutive expression of growth-associated genes or in
      terminally differentiated post-mitotic cells).

PMID- 17180005
TI  - Induction of apoptosis by transiently transfected metabolically stable wt p53 in
      transformed cell lines.
AB  - Biochemical and functional properties of wild-type (wt) and mutant p53 were
      studied under the same cellular environment by transient transfection. Exogenous
      wt p53 expressed in transformed cell lines was found to be as metabolically
      stable as mutant p53. Yet only mutant p53 bound to hsp70 whereas wt p53 did not,
      suggesting that the metabolic stability of p53 does not depend on its ability to
      form complexes with hsp70. The wt protein was expressed essentially in the
      nucleus, while mutant p53 showed both nuclear and cytoplasmic expression, as
      determined by immunofluorescence staining with PAb122. In addition, staining with
      PAb1801 revealed a number of strongly fluorescent cell fragments in cultures
      transfected by wt p53. Morphological features of apoptosis were observed in these
      cultures. Quantitative analysis by flow cytometry confirmed that only the cell
      population expressing wt p53 had a significant amount of cell debris. Thus,
      transient expression of a metabolically stable wt, but not mutant, p53 induces
      cell death by apoptosis. The present study demonstrates a model system to
      investigate the functional domains of p53 in the induction of apoptosis.

PMID- 17180006
TI  - Signals transduced via insulin-like growth factor I receptor (IGF(R)) mediate
      resistance to retinoic acid-induced cell growth arrest in a human neuroblastoma
      cell line.
AB  - Retinoic Acid (RA) has been shown to control growth and induce differentiation in
      a number of human neuroblastoma (NB) cell lines. However, a number of NB cell
      lines may be termed resistant to RA as they fail to growth arrest and
      differentiate. In studying the mechanism mediating RA-resistance, we noted that
      invariably RA-resistant NB cell lines constitutively express Insulin-like Growth
      Factor 2 (IGF2) (Gaetano, 1991b). The NB cell line LAN-1-15N (15N) represented an
      interesting model in which to study the development of RA-resistance as initially
      15N cells are growth arrested by RA, however with prolonged culture (8-10 days)
      cells begin to proliferate. Coincidentally, RA induces IGF2 mRNA and protein
      secretion in 15N NB cells (Matsumoto, 1992). In this study we isolated RA
      resistant 15N cell lines and analyzed their growth properties and changes in cell
      cycle related (cdc2, cdk2, cyclins A, B, D and E) and early response (fos and
      jun) gene expression to evaluate the role IGF2 may play in mediating RA
      resistance. We found that exogenous IGF2 stimulates growth in 15N and is capable
      of altering RA induced inhibition of NB cell growth. Finally we show that by
      blocking the Insulin-like Growth Factor Receptor (IGF1(R)) with a monoclonal
      antibody (alpha-IR3) in the presence of RA the growth of RAR cell lines could be
      completely blocked. These data are consistent with the concept that signals by
      IGF2 and transduced via the IGF1(R) can mediate resistance to the growth
      inhibiting properties of RA.

PMID- 17180008
TI  - Meeting Report: The high-tech aspect of death.

PMID- 17180007
TI  - Immediate and delayed apoptotic cell death mechanisms: UVA versus UVB and UVC
      radiation.
AB  - The mechanism of cell death induced by the different waveband regions of
      ultraviolet radiation (UVR), i.e., UVA1 (340-400 nm), UVB (290-320 nm) and UVC
      (200-290 nm) was investigated, using equilethal doses (90% reproductive death) on
      L5178Y-R murine lymphoma cells. To distinguish between necrosis and apoptosis,
      the following endpoints were monitored over time using flow cytometry and
      transmission electron microscopy: percentage of remaining cells, membrane
      permeabilized cells, dead cells, apoptotic cells, and ultrastructural changes.
      All waveband regions of UVR were found to cause apoptosis as opposed to necrosis.
      However, UVA1-induced immediate (0-4 h) apoptosis, while UVB- or UVC-induced
      delayed apoptosis (<34 h). Moreover, the membrane permeability changes that only
      result from exposure to UVA1 radiation, especially to red blood cells, suggests
      that the immediate apoptotic mechanism involves membrane damage. Therefore, the
      results suggest that there are three death mechanisms available to one cell type:
      necrosis, immediate apoptosis, and delayed apoptosis (or programmed cell death).

PMID- 17180009
TI  - AIDS: A PCD pathology?

PMID- 17180010
TI  - Does apoptosis contribute to CD4 T cell depletion in human immunodeficiency virus
      infection ?
AB  - Despite an extensive knowledge of the molecular characteristics of the human
      immunodeficiency virus (HIV) identified more than ten years ago as the cause of
      AIDS (acquired immune deficiency syndrome) (Barre-Sinoussi et al. 1983) some
      critical questions have not been answered yet: Is the progressive disappearance
      of CD4+ helper T lymphocytes, the hallmark of AIDS, directly related to the
      killing of infected cells by the virus? If not, how do CD4+T cells die? Is HIV
      using its viral factory to kill uninfected bystander cells? What causes the
      immune system collapse in HIV infection? In the past three years some important
      studies have provided stimulating clues suggesting that AIDS is not only related
      to the killing of host cells by HIV but is also a consequence of mechanisms of
      misactivation of the immune system, leading to anergy or apoptosis of non
      infected effector cells. We discuss some of the in vivo and in vitro models
      providing evidence that HIV is able to kill and cripple the immune system either
      by acting directly on its targets or indirectly in bystander T cells keeping in
      mind that HIV disease must be considered as a multifactorial process.

PMID- 17180011
TI  - Programmed cell death and AIDS: significance, perspectives and unanswered
      questions.

PMID- 17180012
TI  - Are CD4 and Fas peptide identities of gp120 relevant to the molecular basis of
      AIDS pathogenesis?
AB  - The release of virions from HIV-1-infected CD4 cells, although occurring readily
      as a result of immune activation, does not appear to be the only mechanism
      mediating T-cell loss in AIDS. Three other interacting HIV-1-induced immune
      disorders in association with viral release (the source of gp120 molecules) may
      also account for the constitutive T-cell depletion and functional immune
      suppression: 1. gp120-induced CD4(+) cell anergy, which can be reproduced in
      cultures of immune activated normal T-cells in the presence of gp120 or gp120
      peptide containing the SLWDQ sequence identity to the CD4 molecule; 2.
      overproduction of IFNalpha and gamma, 3. activation-driven apoptosis of non
      infected T-cells. Apoptosis of T-cells could also be: 1. induced by effector
      components - particularly CTL and lymphotoxins produced by helper T-cells of the
      anti-Fas autoimmune reaction triggered by gp120 epitopes shared with the Fas/APO
      1 molecule; 2. enhanced by IFN overproduction. These molecular mechanisms stress
      the importance in the progression to AIDS of both the viral load and HIV-induced
      cytokine dysregulation, including overproduction of IFNalpha, which should be
      considered as targets in the development of strategies for AIDS prophylaxis and
      immunotherapy.

PMID- 17180013
TI  - A model for the hierarchical structure of the human epidermal cornified cell
      envelope.
AB  - The epidermal cornified cell envelope (CE) is a 15 nm thick layer of highly
      insoluble protein that is assembled on the intracellular surface of the cell
      membrane during terminal differentiation, and comprises about 10% of the mass of
      the cornified dead layers of the tissue. The CE consists of a complex amalgam of
      several known proteins that are crosslinked by isodipeptide bonds formed by the
      action of transglutaminases, but little is known about their order of accretion
      during CE assembly, or how they are crosslinked. In this paper, CEs purified from
      human foreskin epidermis were examined by immunogold electron microscopy before
      and after digestion with proteases.The mass fractions of the proteins remaining
      in CE remnants during digestion were estimated from the amino acid compositions
      by mathematical modelling. Together, the data support a new model for the complex
      hierachical structure of the CE. The cytoplasmic surface of intact purified CEs
      consists of filaggrin, loricrin, SPRs and keratin intermediate filaments. The
      bulk of the CE consists of a mixture of loricrin (75%) and SPRs (5%). Following
      removal of most of these, the novel protein elafin is exposed, which contributes
      about 6% of CE mass. The protein material on the inner CE 'core' adjacent or
      attached to the lipid envelope consists of cystatin alpha (5%), involucrin (2%),
      keratin filaments (3%) and possibly other as yet unidentified protein(s)(2-5%).
      This model supports but considerably extends an earlier extant hypotheis for CE
      structure, and thus provides the basis for further detailed biochemical and ultra
      structural studies.

PMID- 17180014
TI  - Downregulation of the antioxidant defence during glucocorticoid-mediated
      apoptosis.
AB  - Recent studies implicate oxidative stress in the mechanism of apoptosis. We have
      examined the expression of genes, whose products counteract oxidative stress,
      during glucocorticoid-mediated apoptosis of a murine thymoma-derived cell line.
      Using Northern blot hybridisation analyses, we observed a progressive decline
      over a 24 h period in the transcript levels for catalase, manganese superoxide
      dismutase, copper, zinc-superoxide dismutase, DT-diaphorase and thioredoxin. The
      changes were first seen within 2-8 h of the addition of the hormone which is well
      in advance of appreciable apoptosis. Using Western blot hybridisation analyses we
      found that a dexamethasone-mediated increase in glutathione S-transferase message
      level was followed closely by an increase in glutathione S-transferase mu class
      protein and a 20% decrease in reduced glutathione levels. Our findings suggest
      that the downregulation of cellular oxidant defense enzymes with a consequent
      increase in oxidant damage could contribute to the molecular mechanism of
      apoptosis.

PMID- 17180015
TI  - Characterisation of eye-lens DNases: long term persistence of activity in post
      apoptotic lens fibre cells.
AB  - Fibre cells in the ocular lens exhibit a constitutive apoptotic process of
      nuclear degradation that includes chromatin breakage, generating a ladder pattern
      of DNA fragments. This process is intrinsic to the normal terminal
      differentiation program. Despite the loss of nucleus and cytoplasmic organelles,
      the terminal differentiated fibre cells remain in the lens during the whole life
      span of the individual. The lens cells thus provide a unique system in which to
      determine the presence and fate of endonucleases once the chromatin has been
      cleaved. We report here on the presence of DNase activity in nucleated and
      anucleated lens cells. Using a nuclease gel assay and double-stranded DNA as
      substrate, we found active 30 and 60 kDa DNases. The enzymatic activities were
      Ca(2+), Mg(2+) dependent, and active at neutral pH. The relative amount of these
      forms changed during development and aging of the lens fibre cells. Both forms
      were inhibited by Zn(2+), aurintricarboxylic acid, and G-actin. The proteins were
      also separated by SDS-PAGE, renatured after removing SDS and incubated in the
      presence of native DNA adsorbed to a membrane. Therefore it was possible to
      demonstrate, by means of a nick translation reaction, that the enzymes produced
      single strand cuts. Based on these findings we propose that these chick lens
      nucleases are probably related to DNase I.

PMID- 17180016
TI  - Cell-cycle progression and apoptosis in K562 and Molt-4 cells after cell-to-cell
      transmission of HTLV-I: modulation by interferons.
AB  - Human T-cell leukemia virus type I (HTLV-I) is mainly propagated by cell division
      and therefore the virus-driven proliferation of infected cells can represent a
      predisposing condition to final development of adult T-cell leukemia (ATL) in
      vivo. To correlate virus expression and cell cycle progression of recipient cells
      after acute infection with HTLV-I, K562 multipotent erytholeukemia and Molt-4 T
      lymphoma cells were used as recipient cells in a cell-to-cell virus transmission
      model. Cell cycle progression was studied by flow cytometry during one
      duplication cycle of recipient cells and transcription of HTLV-I was evaluated
      during the same time course. The antiproliferative and antiviral effects of
      recombinant interferons alpha, beta and gamma were also evaluated on cell cycle
      progression and HTLV-I expression. Transcription of HTLV-I in immortalised virus
      donor MT-2 T-cells was found to be related to cell cycle. After coculturing
      recipient K562 or Molt-4 cells with lethally irradiated, non-dividing virus-donor
      MT-2 cells, progression into cell cycle of recipient cells was delayed. A pre
      G(1) peak, corresponding to 6-11 % apoptotic cells, was identified in cocultured
      Molt-4/MT-2 cells and not in Molt-4 controls, and was not affected by treatment
      with IFNs. Notably, no such peak was identified either in control or in
      cocultured K562 cells. During this time course, transcription of the viral
      subgenomic mRNA encoding for the env-pX region was prevalently observed.
      Treatment with IFNalpha and especially with IFNbeta at the onset of the cultures
      inhibited the growth of both control and virus-exposed recipient cells. IFNgamma
      was less effective. A clearcut reduction of the percentage of cells entering the
      S phase was observed only after treatment with IFNbeta. At the same time, in
      IFNbeta-treated cocultures a marked inhibition of transcription of viral mRNA was
      observed, suggesting that, during acute infection, treatment with IFNbeta
      contributes to reduce the infection of recipient cells by down-regulating both
      the cellular proliferation rate and virus transcription in infected cells.

PMID- 17180017
TI  - Bcl-2 relieves deoxyadenylate stress and suppresses apoptosis in pre-B leukemia
      cells.
AB  - The influence of bcl-2 activity on 2'-deoxyadenosine-induced apoptosis was
      investigated in 697 human pre-B leukemia cells stably transfected with expression
      plasmid pHeBo-BCL-2alpha (697/BCL2 cells). Apoptosis was induced by the 2'
      deoxyadenosine analogue, 2-chloro-2'-deoxyadenosine (Cl-dA), with the
      concentration for apoptosis in one-half of the cells at 24 hours (LD(50)) being
      10 microM for 697 cells and 120 microM for 697/Bcl 2 cells. There was a strong
      positive correlation between Cl-dATP levels and apoptotic index (coefficient of
      determination, r(2)=0.95; P=0.027). When 697 cell and 697/Bcl 2 cell lines were
      treated with 5 microM Cl-dA, Cl-dATP did not significantly accumulate in the
      latter. The Cl-dATP/dATP ratio was 0.03 in Cl-dA treated 697/Bcl 2 cells but
      nearly 6 in treated 697 cells. Bcl 2 overproduction also suppressed the
      accumulation of dAMP, dADP and dATP in cells exposed to 2'-deoxyadenosine in the
      presence of pentostatin to abrogate the pronounced inversion of ATP/dATP pools
      associated with 2'-deoxyadenosine exposure. These results suggest that one
      consequence of bcl-2 activity is suppression of 2'-deoxyadenosine phosphorylation
      and elevation in the apoptotic target cells. Relief from deoxyadenylate stress
      imbalances implies a novel upstream site of bcl-2 activity.

PMID- 17180018
TI  - Meeting Report: Apoptosis based new approaches to cancer therapy.

PMID- 17180019
TI  - C-Rel: a multifunctional transcription factor ?

PMID- 17180020
TI  - The abl oncogene family and apoptosis.
AB  - The role of the abl oncogene family in cellular transformation has been well
      established, but knowledge of its role in apoptosis is limited. Recent studies
      demonstrate that it may act as a suppressor of apoptosis in certain
      circumstances. The growth factor independence conferred on IL-3 dependent myeloid
      progenitor cell lines following v-Abl transformation is due to the suppressive
      effects of this oncogene on apoptosis. Similarly, inhibition of the deregulated
      activity of the p210(bcr-abl) protein in both myeloid progenitor lines and CML
      granulocytes has proven effective in reversing resistance to apoptosis in such
      cells. The Bcr-Abl fusion protein might therefore promote myeloid expansion by
      suppression of apoptotic cell death rather than through promoting proliferation.
      While oncogenic forms of Abl appear to be anti-apoptotic, the function of c-Abl
      remains elusive. Through the elucidation of the roles in cell growth and survival
      of the Abl family members we may gain valuable insights into the regulation of
      apoptosis and the mechanisms of oncogenesis.

PMID- 17180021
TI  - c-myb down regulation is associated with apoptosis in human neuroblastoma cells.
AB  - The c-myb transcriptional regulator plays a crucial role in the control of
      several proliferative/differentiative processes in haematopoietic cells. Its
      expression and function is not lineage-restricted, since c-myb is also expressed
      in solid tumours such as neuroblastomas, where its transcription is decreased by
      retinoic acid. In response to retinoic acid, neuroblastomas differentiate either
      towards a neuronal phenotype or undergo apoptosis. The temporal relationship
      between reduction in c-myb mRNA levels and the
      differentiative/proliferative/apoptotic processes suggests that c-myb may play a
      key role in the control of growth of these neuroectodermal tumours. Transfection
      of neuroblastoma cells with expression vectors containing segments of human c-myb
      cDNA in antisense orientation yielded fewer transfectant clones, with a far
      slower proliferation rate, than transfection with the corresponding sense
      construct. The dramatic growth arrest and reduction in cell number in the
      antisense transfectants is due to the induction of apoptosis. Apoptosis in the c
      myb antisense-transfected cells is further increased in reduced serum conditions.

PMID- 17180023
TI  - Dose-dependent zinc inhibition of DNA ladder in apoptotic HeLa cells regulates
      the activity of poly(ADP-ribose) polymerase and does not protect from death
      induced by VP-16.
AB  - Zinc ions exert an inhibitory effect on Ca(2+)Mg(2+)-dependent endonuclease which
      is supposed to be responsible for the fragmentation of DNA during apoptosis. In
      the experimental system we used, that is HeLa cells treated with VP-16, the
      protection from internucleosomal DNA degradation is modulated by Zn concentration
      and appears to be dependent on the time after treatment. This effect does not
      prevent cell death or occurrence of apoptotic parameters, suggesting that DNA
      ladder appearance is not a crucial event in apoptosis. The activation of poly(ADP
      ribose)polymerase following the administration of VP-16, is not observed in cells
      in which DNA fragmentation has been abolished by zinc, supporting the hypothesis
      that this event is regulated by the appearance of small-sized DNA fragments.

PMID- 17180022
TI  - Studies on the induction of apoptosis in WEHI 231 cells by pharmacological agents
      and lipid mediators. Sphingosine and ceramide induce apoptosis in WEHI 231.
AB  - We report the results of a systematic study of the effects of pharmacological
      agents known to cause or modify physiological cell death (PCD). Using WEHI 231
      cells as a model, we investigated the effects of dexamethasone, cAMP, selected
      growth factors/ cytokines, DNA damaging agents, metabolic inhibitors and lipid
      mediators. We found that WEHI 231 cells are not affected by cAMP(1-90 microM) or
      TGFbeta (1-50 ng/ml), both of which are known to induce PCD in other systems. We
      also failed to detect protection from PCD in WEHI 231 cells cultured with Zn(++),
      E64 and leupeptin. In contrast, dexamethasone (400 microg/ml), etoposide (10(
      4)M), emetine (10(-5)M), calyculin (10(-5)M), sphingosine (8-16 microM) and
      ceramide (20-40 microM) all cause PCD in WEHI 231 cells. The effects of ceramide
      can be blocked by LPS but not by overexpression of bcl2.The role of killer lipids
      in PCD is discussed.

PMID- 17180024
TI  - Cellular localization of the bcl-2 protein and response to glucocorticoid stress.
AB  - We performed immunoelectronmicroscopy, immunofluorescence and subcellular
      fractionation studies of insect cells (Spodopetra frugiperda or SF9) infected
      with recombinant baculovirus containing bcl-2 cDNA to determine the cellular
      localization of the bcl-2 product. Similar studies were also undertaken in pre-B
      cells carrying a bcl-2 gene activated by t(14;18) chromosomal translocation. By
      immunogold electron microscopy, bcl-2 was localized at several intracellular
      sites including the nuclear membrane, endoplasmic reticulum, mitochondria and
      plasma membrane. Immunofluorescence studies revealed the presence of the bcl-2
      product throughout the cytoplasm, whereas biochemical fractionation studies
      indicated a similar pattern to that observed on electron microscopy. Our
      investigation clearly indicates that the bcl-2 product is expressed at several
      intracellular sites. Studies were also undertaken to determine any changes in the
      subcellular distribution of bcl-2 protein following glucocorticoid exposure of
      immature B lymphocytes. Although no major changes in the distribution of bcl-2
      protein were observed, more aggregated patches of gold labelled bcl-2 particles
      were found under glucocorticoid stress. Aggregation of bcl-2 molecules might
      represent dimerization necessary to prevent apoptosis.

PMID- 17180025
TI  - Applied Sciences: Absence of CD44-standard in human neuroblastoma correlates with
      histological dedifferentiation, N-myc amplification and reduced survival
      probability.
AB  - Expression of CD44 was examined by immunohistochemistry in 205 primary
      neuroblastomas together with histological grading according to the Shimada
      classification at the time of diagnosis. In addition, Southern blot analysis to
      determine N-myc gene amplification was carried out in the same tissue. When
      compared with clinical data such as stage, age and event-free survival
      probability it was found that CD44 expression characterizes well differentiated
      tumours and thus correlates with prognosis (event-free survival probability in
      CD44 positive patients 0.6 (n = 129) vs. 0.0 (n = 21) in CD44 negative patients).
      In tumours with N-myc = 1, CD44 positivity was found in 91% of patients as
      compared to 57% of patients with N-myc > 1 in tumours. All tumours of 13 patients
      with metastatic stage 4s (with good prognosis) showed CD44s expression. Thus,
      detection of CD44s expression might serve as a prognostic indicator which can be
      rapidly detected at diagnosis.

PMID- 17180026
TI  - Cell death in muscle pathology.

PMID- 17180027
TI  - The effect of p53 status on the radiosensitivity of haemopoietic stem cells.

PMID- 17180028
TI  - Post-ischemic apoptotic death of rat neonatal cardiomyocytes.
AB  - Despite the clinical importance of cardiomyocyte death following ischemia and
      reperfusion, little is known about the nature of the process. In primary rat
      neonatal cardiomyocyte cultures, cell death was induced by ischemia (deprivation
      of oxygen, serum and glucose) and reperfusion. We report here that ischemia
      induced primarily necrosis, whereas subsequent reperfusion induced apoptosis.
      Apoptosis of rat neonatal cardiomyocytes could not be prevented by protein
      synthesis inhibitors, suggesting that molecular components of the apoptotic
      pathway pre-exist in these cells. IGFs and calpain inhibitors had no effect on
      necrotic death during ischemia, but they significantly reduced apoptotic death
      during reperfusion. These results support the concept that inhibition of post
      ischemic apoptotic death in the myocardium may provide a valuable new therapeutic
      strategy for the treatment of acute myocardial ischemia.

PMID- 17180029
TI  - Programmed cell death in dystrophic (mdx) muscle is inhibited by IGF-II.
AB  - The pathology of Duchenne Muscular Dystrophy (DMD) is characterised by unstable
      muscle fibres and by increased cell turnover due to the absence of functional
      dystrophin protein. We have used skeletal muscle, primary muscle stem cell
      cultures (Smith and Schofield, 1994; Smith et al., paper submitted) and clonal
      cell lines of the mouse DMD model (mdx) and its congenic control (C57BI) to
      demonstrate that programmed cell death (PCD) and apoptotic morphology is
      increased in dystrophic (mdx) muscle and in cultured muscle cells. We also show
      that the peptide growth factor (IGF-II), which is thought to play a role in
      mammalian myogenesis, reduces PCD in mammalian skeletal muscle myoblasts both in
      vivo and in vitro. This is the first time that apoptosis or PCD have been
      demonstrated in normal mammalian skeletal muscle. We discuss the potential of
      this system in determining the role of PCD in mammalian myogenesis and skeletal
      muscle maturation, its significance in dystrophic muscle, and suggest a novel
      therapeutic route whereby the pathology of DMD may be alleviated using the
      survival properties of IGF-II.

PMID- 17180030
TI  - Inhibition of ceramide-induced apoptosis by Bcl-2.
AB  - Ceramide, a long chain sphingolipid that is generated intracellularly upon
      hydrolysis of membrane-associated sphingomyelin, has recently been implicated as
      a second messenger-like molecule that is produced distal to ligation of the
      tumour necrosis factor receptor type 1 (TNFR1), as well as the related Fas
      (CD95/Apo-1) molecule. It is well established that ligation of TNFR1 or Fas leads
      to apoptosis in most cases. Furthermore, it has also recently been demonstrated
      that exposure to cell-permeable synthetic ceramides can result in apoptosis in
      many cases. These and other observations have led to the hypothesis that
      accumulation of intracellular ceramide may be a common element of several
      pathways that result in apoptosis. Here we show that exposure to synthetic
      ceramides triggers apoptosis in the human T lymphoblastoid cell lines, CEM and
      Jurkat, and that overexpression of the apoptosis-repressor protein, Bcl-2,
      renders these cells resistant to the apoptosis-inducing effects of ceramide, as
      well as to several other stimuli. Since exposure to ceramides can result in
      either cell proliferation, differentiation, cycle arrest, or death, the level of
      Bcl-2 expression in a cell may be an important factor in determining the outcome
      of signals that result in intracellular generation of this sphingolipid.

PMID- 17180031
TI  - Modulation of apoptosis by starvation: morphological and biochemical study of rat
      intestinal mucosa.
AB  - Morphology at light and electron microscopic levels, expression and activation of
      transglutaminase and DNA fragmentation at internucleosomal sites were used as
      markers to study the effect of starvation on the apoptosis of small intestinal
      epithelial cells. The cells entering apoptotic programme in well-fed animals
      undergo many morphological changes in apical cytoplasm involving alterations in
      actin cytoskeleton organisation which may cause a discharge of microvilli. Some
      free floating cells in the intestinal lumen show characteristics of apoptotic
      cell death, e.g. shrinkage of cell and peripheral condensation of chromatin,
      while mitochondria and lysosomes remain unchanged. Apoptotic bodies are also seen
      in scanning electron micrographs. During progressive starvation, epithelial cells
      do not enter the apoptotic cell death programme. Biochemical markers for
      apoptosis such as increased transglutaminase activity and DNA fragmentation are
      clearly discernible in normally fed animals. The percentage of cells labelled
      immunohistochemically by antibody against transglutaminase decreased during
      starvation while DNA fragmentation was absent. The exact mechanism for
      suppressing apoptosis in intestinal cells under starvation is not known. However,
      the data presented here support the existence of such a regulatory process.

PMID- 17180032
TI  - Inactivation of p53 is associated with decreased levels of radiation-induced
      apoptosis in medulloblastoma cell lines.
AB  - Radiation is the primary therapeutic modality for children with medulloblastoma,
      a pediatric brain tumour. We examined the response of four medulloblastoma cell
      lines to ionising radiation. Our evaluation utilising flow cytometry,
      morphological analysis and terminal deoxynucleotidyl transferase assays
      demonstrated that medulloblastoma cells undergo radiation-induced apoptosis. p53
      mediates radiation-induced apoptosis in many cell types, and p53 mutations have
      been associated with increased resistance to ionising radiation. p53 mutations
      are rare in medulloblastoma. We found that wildtype p53 is required for high
      levels of apoptosis in medulloblastoma, and cell lines in which p53 had been
      inactivated by mutation had very low levels of apoptosis. Inactivation of
      endogenous wildtype p53 in medulloblastoma cells by introduction of a dominant
      negative mutant of p53 decreased the level of radiation-induced apoptosis. Our
      results suggest that the sensitivity of medulloblastoma to irradiation involves
      p53-mediated apoptosis and that p53 gene status may be a predictor of response to
      radiation therapy.

PMID- 17180033
TI  - Expression and activity of cell cycle regulators during proliferation and
      programmed cell death in the mammary gland.
AB  - In the mammary gland distinct phases of proliferation, differentiation and
      programmed cell death of epithelial cells occur at defined stages of development.
      Here we show that the expression and activity of cell cycle regulators during
      normal and preneoplastic proliferation and programmed cell death are remarkably
      similar. In all cases we found elevated levels of a protein kinase A activity and
      of transcription factor AP-1, cFos and JunD being the major components of the AP
      1 DNA binding complex. A correlation between cFos and JunD expression and
      chromosomal DNA fragmentation during programmed cell death was observed. Several
      genes associated with G1, including cyclin D1, D2 and D3 and c-fos, c-jun, junB,
      JunD, c-myc and p53, are induced in proliferating and in apoptotic mouse mammary
      tissue. Whereas the expression of these genes correlated with active
      proliferation of epithelial cells in terminal end buds during puberty, very
      little proliferation or DNA synthesis, but, instead, extensive apoptosis of
      epithelial cells, was observed during involution. Our results suggest that a G1
      like state is associated with programmed cell death of mammary epithelial cells
      in vivo and that apoptosis occurs without S-phase induction.

PMID- 17180034
TI  - Apoptosis in a unicellular eukaryote (Trypanosoma cruzi): implications for the
      evolutionary origin and role of programmed cell death in the control of cell
      proliferation, differentiation and survival.
AB  - The origin of programmed cell death (PCD) has been linked to the emergence of
      multicellular organisms. Trypanosoma cruzi, a member of one of the earliest
      diverging eukaryotes, is a protozoan unicellular parasite that undergoes three
      major differentiation changes and requires two different hosts. We report that
      the in vitro differentiation of the proliferating epimastigote stage into the
      G0/G1 arrested trypomastigote stage is associated with massive epimastigote death
      that shows the cytoplasmic and nuclear morphological features and DNA
      fragmentation pattern of apoptosis, the most frequent phenotype of PCD in
      multicellular organisms. Apoptosis could be accelerated or prevented by modifying
      culture conditions or cell density, indicating that extracellular signals
      influenced the epimastigote decision between life and death. Epimastigotes
      responded to complement-mediated immunological agression by undergoing apoptosis,
      while undergoing necrosis in response to nonphysiological saponin-mediated
      damage. PCD may participate into the optimal adaptation of T. cruzi to its
      different hosts, and the avoidance of a local competition between a G0/G1
      arrested stage and its proliferating progenitor. The existence of a regulated
      cell death programme inducing an apoptotic phenotype in a unicellular eukaryote
      provides a paradigm for a widespread role for PCD in the control of cell
      survival, which extends beyond the evolutionary constraints that may be specific
      to multicellular organisms and raises the question of the origin and nature of
      the genes involved. Another implication is that PCD induction could represent a
      target for therapeutic strategies against unicellular pathogens.

PMID- 17180036
TI  - The early intracellular production of a reactive oxygen intermediate mediates
      apoptosis in dexamethasone-treated thymocytes.
AB  - Many conditions that induce an oxidative stress are capable of evoking apoptosis.
      This has lead to the proposal of oxidative stress as a mediator of apoptosis. We
      show that, in murine thymocytes, oxidative stress and apoptosis occur in the same
      cell. We identified four distinct apoptotic subpopulations that appeared
      sequentially in time. Catalase protected from dex-amethasone-induced death in the
      initial stages of apoptosis, while iron chelators and Vitamin E did not. Further
      studies provided evidence supporting the early production of an intracellular
      oxidative intermediate as an obligatory step for the efficient induction of
      apoptosis. We propose that at least one of the molecules capable of filling this
      role is hydrogen peroxide.

PMID- 17180035
TI  - Mechanisms controlling death, survival and proliferation in a model unicellular
      eukaryote Tetrahymena thermophila.
AB  - Below a critical cell density of 750 cells ml(-1), and in a manner familiar
      throughout much of cell culture technology, Tetrahymena thermophila die within a
      few hours despite being supported by a nutritionally complete synthetic medium,
      SSM, in which a supracritical inoculum (1000 cells ml(-1)) nevertheless
      proliferates and quickly reaches 1 x 10(6) cells ml(-1). The kinetics of cell
      death, and the conditions required to keep cells alive at and below the critical
      density have now been more fully investigated. Interestingly, cell death follows
      first order kinetics, with a half-life of less than two hours at 250 cells ml(
      1). Survival can be extended by an order of magnitude, however, when protein
      synthesis is reduced by inoculation of cells at this density in: (a)Tris/HCI
      buffer;(b) SSM deficient in an essential amino acid (arginine or phenylalanine);
      or, (c) SSM containing cycloheximide. In the presence of actinomycin D, the
      critical density required for proliferation can be lowered to 100 cells ml(-1).
      These results are discussed in relation to the capacity of Tetrahymenaio produce
      and release signal molecules (loosely referred to as growth factors), which need
      to be present above a certain threshold level before proliferation occurs. The
      evidence for the demise of cells at low density being active - in terms of
      requirement for, or dependency on, new transcriptional and translational
      processes - is discussed, along with more general implications of the findings
      for the control of cell death in populations of 'free-living' unicellular
      organisms in culture compared with their normal habitats.

PMID- 17180037
TI  - Comparative cytotoxic effects of two protein phosphatase inhibitors, okadaic acid
      and calyculin A, on thyroid cells.
AB  - The cytotoxicity of two inhibitors of protein phosphatases PP1 and PP2A has been
      investigated on primary cultures of dog thyrocytes. Both compounds, okadaic acid
      and calyculin A elicited dose- and time- related effects, i.e. apoptosis and
      necrosis. In addition a pronounced detachment of the cells from the monolayer was
      also observed. Based on the different patterns of morphological alterations and
      on the biochemical data, it was concluded that each compound induced different
      types of cell death; this provides additional evidence that a specific cell type
      can initiate distinct programs of death depending on the triggering stimulus. To
      explain the effects recorded when both compounds were added concomitantly, a
      functional interaction between PP1 and PP2A has been proposed. Finally, all the
      effects appeared modulated, to different extent, by cycloheximide and by
      actinomycin D. This supports the view that de novo RNA synthesis is required for
      the induction of death by these phosphatase inhibitors in these cells.

PMID- 17180038
TI  - Role of c-fes protooncogene in myeloid differentiation.
AB  - The main purpose of this report is to provide a review of the present knowledge
      on the structure, function, and possible regulatory role of c-fes in the genetic
      programs underlying the proliferation and differentiation of hematopoietic
      myeloid cells. Fes encodes a non-receptor tyrosine kinase that is highly
      expressed in immature and differentiated cells of the granulocytic and mono
      macrophagic lineages. It is therefore possible that c-fes is involved in the
      signal transduction of myeloid cell differentiation, even if the specific
      substrates phosphorylated by this protooncogene are only poorly characterised.
      Several experimental models have been established to evaluate the role of c-fes
      in myeloid differentiation, in particular: the differentiation capacity of HL60
      cells lacking the p92(c-fes) protein, the transfection of c-fes gene into K562
      cells and transgenic animals overexpressing c-fes. The results obtained point to
      the importance of c-fes in myeloid cells, since it appears to be involved in
      granulocytic maturation as an antiapoptotic gene, and in macrophagic maturation
      as a regulatory gene.

PMID- 17180039
TI  - Cell surface sialylation plays a role in modulating sensitivity towards APO-1
      mediated apoptotic cell death.
AB  - APO-1/Fas(CD95), a member of the tumour necrosis factor (TNF)/nerve growth factor
      (NGF) receptor superfamily transduces apoptotic signals into apoptosis sensitive
      cells. In metabolic labelling experiments using the highly APO-1 positive cell
      lines HUT78 (adultT cell leukemia) and SKW6.4 (Blymphoblastoid cell line) APO-1
      was characterised as a long living protein with a complex glycosylation pattern
      involving terminal sialic acid groups which account for 8-kDa of its apparent
      molecular weight on SDS-PAGE. APO-1 expression and the degree of sialylation were
      determined in additionalT and B cell lines. On the group I Burkitt's lymphoma
      cell line BL60 transfected with human APO-1 (K50) low sialylated species were
      detected only on the cell surface, suggesting that sialylation might be
      functionally important. Removal of terminal sialic acid groups by treatment of B
      and T cell lines with Vibrio cholerae neuraminidase (VCN) augmented sensitivity
      towards anti-APO-1 and human APO-1 ligand induced apoptosis. Similarly, VCN
      treated U937 cells were rendered more sensitive to TNFalpha-induced cell death.
      Thus, sialylation may be one mechanism to regulate sensitivity towards ligand
      mediated cell death in this receptor family.

PMID- 17180040
TI  - Biochemical and functional comparisons of Mcl-1 and Bcl-2 proteins: evidence for
      a novel mechanism of regulating Bcl-2 family protein function.
AB  - Mcl-1 is a recently described homologue of Bcl-2 whose function and biochemical
      characteristics remain poorly defined. Gene transfer experiments in lnterleukin-3
      (IL-3)-dependent myeloid progenitor 32D.3 cells and pro-B-lymphoid FL5.12 cells
      demonstrated that enforced production of high levels of Mcl-1 protein failed to
      prolong the survival of cells when cultured in the absence of IL-3, whereas Bcl-2
      did delay cell death. Mcl-1 also did not prolong the survival in vitro of 32D.3
      cells that had been induced to differentiate into mature neutrophils using
      Granulocyte-Colony Stimulating Factor (G-CSF), whereas Bcl-2 did. 32D.3 and
      FL5.12 cells co-transfected with Mcl-1 and Bcl-2 displayed survival kinetics
      essentially identical to cells transfected with Bcl-2 alone, when cultured in the
      absence of IL-3, indicating that Mcl-1 neither enhances nor impairs Bcl-2
      function. In contrast to the lack of effects of Mcl-1 in 32D.3 and FL5.12 cells,
      Mcl-1 (like Bcl-2) was able to neutralise Bax-induced cytotoxicity in yeast (S.
      cerevisiae). Moreover, the recombinant GST-Mcl-1 protein bound specifically to in
      vitro translated Bax protein, as well as to Bax protein present in detergent
      lysates prepared from 32D.3 and FL5.12 cells, based on in vitro binding assays.
      However, Mcl-1 and Bax proteins could not be co-immunoprecipitated from control
      and transfected 32D.3 and FL5.12 cells, whereas Bcl-2 and Bax were easily co
      immunoprecipitated under the same conditions. The findings suggest that while Mcl
      1 has the capacity to bind to and neutralise the cell death promoting activity of
      Bax, other factors such as perhaps additional proteins or undefined post
      translational modifications may influence its ability to bind to Bax in vivo and
      thus affect its function as a cell death blocker.

PMID- 17180041
TI  - UV-induced apoptosis in skin equivalents: inhibition by phorbol ester and Bcl-2
      overexpression.
AB  - To determine the role of apoptosis in epidermal homeostasis and to identify its
      regulators in skin, we have developed and characterised a physiologically
      relevant in vitro model of epidermal apoptosis. First, we show that keratinocyte
      cell death can be induced by ultraviolet irradiation within the stratified
      epidermis of the skin equivalent in an in vivo-like manner. DNA fragmentation and
      changes in the patterns of expression of p53 and Bcl-2 suggest that the
      mechanisms operating in UV-induced apoptosis in the skin equivalent are
      controlled by these factors. Secondly, we demonstrate that apoptosis in this
      model is amenable to modulation by exogenous factors present in the culture
      medium, such as phorbol ester, and by tranfected genes, as shown by
      overexpression of bcl-2. These studies show that the skin equivalent is a
      valuable model in which to determine the controllable steps of the apoptotic
      pathway independently of the immune system and to correlate apoptosis to the
      physiologic state of the keratinocyte.

PMID- 17180042
TI  - Activation and possible involvement of calpain, a calcium-activated cysteine
      protease, in down-regulation of apoptosis of human monoblast U937 cells.
AB  - An active form of calpain mu, a low-Ca(2+)-requiring intracellular cysteine
      protease, was detected using a cleavage site-directed antibody in apoptotic human
      monoblast U937 cells treated with tumor necrosis factor-alpha and interferon
      gamma. Membrane-permeable calpain inhibitors accelerated apoptosis of U937 cells
      thus induced and suppressed the activation of procalpain. These findings suggest
      that calpain down-regulates apoptosis by shutting off the intracellular signals
      for cell death.

PMID- 17180043
TI  - DNA synthesis precedes gliotoxin-induced apoptosis.
AB  - The toxin gliotoxin induces apoptosis or programmed cell death in a variety of
      immune cells including thymocytes. Apoptosis induced by gliotoxin in thymocytes
      is unaffected by protein synthesis inhibitors nor is it associated with early
      changes in intracellular calcium levels (Beaver and Waring, 1994). This work
      shows that the cell lines P815 and WEHI7 and murine thymocytes when treated with
      gliotoxin show an early incorporation of tritiated thymidine over the
      concentration range which causes apoptosis. Proliferating cell nuclear antigen
      (PCNA), a marker for S phase, is elevated in cells following gliotoxin treatment
      and S phase DNA content is increased. Thymidine incorporation is inhibited by
      hydroxyurea, an inhibitor of replicative DNA synthesis not repair. Free radical
      scavangers have no effect on apoptosis induced by gliotoxin in thymocytes.
      Hydrogen peroxide-treated cells showed no enhanced thymidine incorporation and no
      apoptosis. Thus oxidative stress does not appear to be a factor in gliotoxin
      induced apoptosis. Thymocytes treated with gliotoxin show increased
      phosphorylation of a 16.3 kDa protein, and apoptosis is inhibited by the tyrosine
      kinase inhibitor genistein, which also inhibited the increased thymidine
      incorporation in P815 cells. We conclude that one mechanism by which gliotoxin
      can cause apoptosis may be the induction of inappropriate entry of cells into the
      cell cycle followed by death.

PMID- 17180044
TI  - The rodent non-genotoxic hepatocarcinogen Nafenopin and EGF alter the
      mitosis/apoptosis balance promoting hepatoma cell clonal growth.
AB  - The responses of a series of rat hepatoma cell lines (FaO, HTC, RH1) to the
      rodent non-genotoxic hepatocarcinogen and per-oxisome proliferator (PP) Nafenopin
      were studied to determine if this PP acts with EGF, a naturally occurring liver
      growth regulator, to perturb the balance between mitosis and apoptosis. EGF
      enhanced the growth of FaO cells (well differentiated) and HTC cells
      (intermediate differentiation) but not of the poorly differentiated RH1 cell
      line. Nafenopin also increased FaO cell growth but, surprisingly, retarded the
      growth of both HTC and RH1 cells. Since population expansion kinetics result from
      mitosis and death, replicative DNA synthesis (RDS) and apoptotic cell death were
      measured in HTC cells. As expected, EGF elevated RDS and suppressed cell death.
      However, Nafenopin depressed HTC net population expansion via a suppression of
      cell death coupled to a more marked inhibition of RDS. This apparent paradox was
      investigated using soft agar cloning. This revealed sub-populations with
      differing growth kinetics suggesting selective clonal expansion via an alteration
      in the balance between mitosis and apoptotic cell death. At later stages, cells
      are refractory to EGF and Nafenopin, suggesting that genetic changes may have
      superseded such factor-dependence.

PMID- 17180045
TI  - Meeting Report: Apoptosis: is it a digestive problem?

PMID- 17180047
TI  - Normal hepatocytes or foie gras?

PMID- 17180046
TI  - Viruses hold the keys of death.

PMID- 17180048
TI  - O(2( )) Wanted: dead or alive.

PMID- 17180049
TI  - Anti-apoptotic genes of baculoviruses.
AB  - Baculoviruses possess two different classes of genes with anti-apoptptic
      activity: p35 and iap. The p35 gene product (P35) is able to block apoptosis
      induced by a variety of stimuli in phylogenetically diverse organisms. P35 has
      recently been shown to be capable of inhibiting the ICE/ced-3 family of cysteine
      proteases, a family of enzymes which are implicated in cell death and which
      exhibit specificity for cleavage at aspartate residues. The products of the iap
      genes are a distinct class of proteins containing a carboxyl ring finger and
      tandem duplications of a unique motif known as the BIR motif. Homologues of the
      baculovirus iap genes have been identified in the human genome. Both classes of
      baculovirus anti-apoptotic genes will continue to be important tools in defining
      the pathways involved in apoptosis. Since our demonstration in 1991 that a
      baculovirus prevents host cells from undergoing apoptosis by expressing a gene
      known as p35(Clem et al., 1991), the study of baculovirus-induced apoptosis and
      the anti-apoptotic genes they possess has led to discoveries with far-reaching
      implications for viral pathogenesis, human disease, and the study of cell death.
      It is now known that a variety of eukaryotic viruses encode genes which allow
      them to control cellular apoptosis. Understanding the mechanism(s) by which these
      viral gene products act provides fundamental insights into the pathways
      regulating apoptosis. In this review, we discuss the inhibition of apoptosis by
      baculoviruses, concentrating mainly on the nature and mechanism of action of the
      two classes of baculovirus genes, p35 and iap, which are able to control
      apoptosis in a diversity ofeukaryotes.

PMID- 17180050
TI  - Cell proliferation, cell death and hepatocarcinogenesis.
AB  - The carcinogenic process in the liver is a multistep process, characterised by an
      altered ratio between cell proliferation and cell death. In the last few years,
      we have undertaken studies aimed at determining the possible differences
      exhibited by two different types of cell proliferation, namely compensatory
      regeneration and direct hyperplasia at a molecular and cellular level. These two
      types of proliferative stimuli appear to play different roles in liver
      carcinogenesis. The scope of this article is to summarise the present knowledge
      about the differences in the expression of genes involved in the entry of liver
      cells into cell cycle, between liver regeneration following cell loss and/or cell
      death and direct hyperplasia induced by primary mitogens.

PMID- 17180051
TI  - Hepatocyte growth factor is a pleiotropic factor protecting epithelial cells from
      apoptosis.
AB  - Hepatocyte Growth Factor (HGF) is a pleiotropic factor, capable of evoking
      complex biological responses such as mitogenesis, motogenesis and morphogenesis
      in a variety of epithelial and endothelial cells. Nonetheless, the meaning of the
      acronym is consistent with the key role of the factor in liver regeneration, in
      vivo and in liver development during embryogenesis. The receptor for HGF is the
      tyrosine kinase encoded by the c-MET proto-oncogene. Upon ligand binding, the
      receptor kinase is activated by tyrosine autophosphorylation and recruits
      cytoplasmic transducers involved in HGF-triggered signal transduction. We
      investigated the role of HGF as a survival factor in protecting cells from
      apoptosis and we show that HGF is able to counteract staurosporin-induced
      apoptosis of epithelial cells.

PMID- 17180052
TI  - C/EBPbeta is required for the late phases of acute phase genes induction in the
      liver and for tumour necrosis factor-alpha, but not Interleukin-6, regulation.
AB  - C/EBPbeta is a leucine-zipper transcription factor believed to play an important
      role in the control of liver functions, and in particular in the transcriptional
      regulation of acute phase genes in response to several inflammatory stimuli and
      to recombinant cytokines. Moreover, this factor has been proposed as an important
      activator of several cytokine genes. We recently described the generation of mice
      in which the C/EBPbeta gene has been inactivated by gene targeting, showing that
      they are viable, but present specific defects in the myeloid and lymphoid
      compartments. Here we demonstrate that C/EBPbeta does indeed play a role in the
      transcriptional induction of some, but not all, liver acute phase genes.
      Activation is in particular defective in C/EBPbeta-deficient mice in the later
      phases of induction, suggesting that the early phases may be triggered by factors
      other than C/EBPs. Moreover, IL-6 activation is normal and TNFalpha activation is
      defective in the mutant mice, indicating a differential role of C/EBPbeta in the
      control of these two cytokines' production.

PMID- 17180053
TI  - Two RAREs and an overlapping CRE are involved in the hepatic transcriptional
      regulation of the Q10 MHC class I gene.
AB  - The Q10 gene is a member of the major histocompatibility complex of the mouse
      that is expressed in the liver and kidney of the adult. Using transient
      expression assays, we found that the Q10 promoter was activated by retinoic acid
      (RA) and exogenous RARs and/or RXRs in a cell type-dependent manner. In addition,
      the basal activity of the Q10 promoter in HepG2 cells is lowered by expressing a
      dominant negative form of RARalpha. Incidentally, we have identified two cis
      elements which consist of sequences related to retinoic acid response elements
      (RAREs) and a putative cAMP responsive element (CRE) the sequence of which
      overlaps one of the RAREs. RAR, RXR, CREB-ATF, and COUP-TF factors bind these
      elements and/or affect their activity. We also demonstrate that the CRE mediates
      part of the stimulation induced by activation of the cAMP pathway on the Q10
      promoter, the residual activation being mediated by RARs. Our results suggest
      that Q10 expression in liver depends upon RA and the interaction between nuclear
      receptors that are expressed in this organ. The overlapping of the CRE with one
      of the RAREs together with the results of PKA activation also suggest that RA and
      cAMP signalling pathways are linked.

PMID- 17180054
TI  - Rapid activation of latent transcription factor complexes reflects initiating
      signals in liver regeneration.
AB  - Liver regeneration following partial hepatectomy represents a physiologic
      response to a growth stimulus occurring in the intact animal. Understanding what
      growth factors and cytokines trigger liver regeneration will provide insights
      into recovery from hepatic injury mediated by viruses and toxins, and promote an
      understanding of normal cellular growth control. The modification of pre-existing
      latent transcription factors in the remnant liver by extracellular signals
      immediately post-hepatectomy provides a mechanism for the transcriptional
      activation of primary or immediate early growth response genes, thereby
      establishing a transcriptional cascade. Two factors activated within minutes to
      hours post-hepatectomy in a protein synthesis-independent fashion include PHF/NF
      kappaB and Stat3. Interestingly, these factors are commonly activated by
      cytokines such as TNFalpha, IL-1 and IL-6 suggesting that there may be a
      connection between cytokine release and the onset of liver regeneration. In
      addition to these known transcription factor complexes, we have used a reporter
      gene assay in transgenic mice to attempt to identify promoter sequences that are
      responsible for the transcriptional activation of the liver-restricted IGFBP-1
      immediate early gene within minutes posthepatectomy. Studies so far indicate that
      an upstream region of 800 bp is able to confer both tissue-restricted expression
      and induction during liver regeneration. Identification of the transcriptional
      activators or liver regeneration factors responsible for this induction will
      result in further dissection of the initiating signals.

PMID- 17180055
TI  - Intracellular redox changes during apoptosis.
AB  - In the current paradigm for apoptotic cell death, the activity of a family of
      proteases related to interleukin 1-beta converting enzyme (ICE) orchestrates the
      multiple downstream events (such as cell shrinkage and chromatin degradation)
      that comprise apoptosis. A variety of stimuli can induce this type of cell death.
      One of the most reproducible inducers is mild oxidative stress, although it is
      unclear how an oxidative stimulus activates ICE-like proteases. Oxidative
      modification of proteins and lipids have also been observed in cells undergoing
      apoptosis in response to non-oxidative stimuli, suggesting that intracellular
      oxidation may be a general feature of the effector phase of apoptosis. However,
      attempts to consistently detect a requirement for reactive oxygen species in
      apoptosis have been inconclusive. Recent experiments revealing that apoptosis is
      typically accompanied by a depletion of intracellular reduced glutathione (GSH)
      are also discussed. In JURKATT lymphocytes treated with antibodies to the Fas/APO
      1 surface receptor, this depletion results from an accelerated efflux of the
      reduced thiol rather than any intracellular oxidation. As GSH is the most
      abundant cytosolic reductant, we propose that its efflux may provide a non
      oxidative mechanism by which the reducing environment of apoptotic cells is lost.
      An increase in oxidative damage to proteins and lipids would then result even in
      the absence of an increase in the production of oxidants. This may explain the
      seemingly contradictory findings that increased oxidative stress is not required
      for apoptosis even though antioxidants often inhibit the process and peroxidised
      products accumulate in apoptotic cells.

PMID- 17180056
TI  - Modulation of the antioxidant defence as a factor in apoptosis.
AB  - This review focuses on evidence that oxidative stress during apoptosis is
      controlled, at least in part, by modulating cellular antioxidant defences.
      Evidence is presented from studies of apoptosis induced by glucocorticoids, HIV-1
      infection and tumour necrosis factor-alpha. Glucocorticoid treatment of murine
      lymphocyte cell lines leads to the down-regulation of primary antioxidant defence
      enzymes, including catalase, superoxide dismutases, thioredoxin and DT
      diaphorase. Following HIV-1 infection, disturbances in glutathione metabolism are
      seen, and decreased antioxidant enzyme activities have been reported for HIV-1
      infected cell lines. The viral protein Tat may mediate these effects. Cellular
      resistance to apoptosis induced by tumour necrosis factor-alpha is modulated by
      the expression of manganese superoxide dismutase or Bcl-2. The loss of
      antioxidant defences is predicted to lead to oxidative stress, which could
      contribute to the mechanism of apoptosis through an effect on redox-sensitive
      transcription factors, calcium homeostasis or cysteine proteases.

PMID- 17180057
TI  - Free radicals and neuronal cell death.
AB  - Production of oxygen free radicals is a natural consequence of aerobic metabolism
      and they are constantly generated in vivo by chemical reactions and metabolic
      processes. Antioxidant defence systems scavenge and minimise the formation of
      oxygen-radical-derived biochemical products, however, these defences are not
      completely effective even under normal physiological conditions. In pathologic
      situations, oxygen free radicals can be generated in excess of a cell's
      antioxidant capacity resulting in severe damage to cellular constituents
      including proteins, DNA and lipids. The inherent biochemical and physiological
      charateristics of the brain, including high lipid concentrations and energy
      requirements, make it particularly susceptible to free radical mediated insult.
      Increasing evidence indicates that many neurological disorders may have
      components of free radical and oxidative stress induce injury.

PMID- 17180058
TI  - The role of hydrogen peroxide and RRR-alpha-tocopherol in smooth muscle cell
      proliferation.
AB  - Oxidants can be considered early growth signals, since they have been shown to
      activate a number of pathways that are also stimulated by growth factors. In
      particular, H(2)O(2) activates the protein kinase C signal transduction pathway
      in smooth muscle cells. These events certainly play a role in the activation of
      the DNA synthesis machinery although it is still unclear whether they can also
      regulate the lethal response. Evidence exists of an oxidant-mediated increase in
      tyrosine protein phosphorylation as an early event in the signal transduction
      cascade of growth factor receptors, leading to augmentation of cell
      proliferation. Oxidants can also induce transcription of enzymes, such as
      ornithine decarboxylase and the phosphatase CL-100. CL-100 is the first example
      of a new class of protein phosphatases responsible for modulating the activation
      of MAP kinase following exposure of quiescent cells to growth factors and further
      implicates MAP kinase activation/deactivation in the cellular response to
      hydrogen peroxide. Moreover H(2)O(2) activates the MAP kinase cascade by
      stimulating the tyrosine kinase and protein kinase C pathways. JNK1, a relative
      of the MAP kinase group, is activated by dual phosphorylation at Thr and Tyr
      during the UV response. RRR-alpha-tocopherol and RRR-beta-tocopherol have
      different and competing effects on smooth muscle cell proliferation, indicating
      that they do not act as antioxidants. The earliest event brought by RRR-alpha
      tocopherol in the signal transduction cascade contolling receptor mediated cell
      growth is the inhibition of the transcription factor AP-1, activated by phorbol
      esters. RRR-beta-tocopherol alone is without effect but in combination with RRR
      alpha-tocopherol prevents the AP-1-inhibiting effect of the latter. Protein
      kinase C is inhibited by RRR-alpha-tocopherol and not by RRR-beta-tocopherol,
      which also in this case prevented the effect of RRR-alpha-tocopherol. The
      inhibition of RRR-alpha-tocopherol of protein kinase C is not the consequence of
      a direct interaction but is due to a diminution, produced by RRR-alpha-tocopherol
      of the kinase phosphorylation. A tocopherol binding protein appears to be at the
      basis of the RRR-alpha-tocopherol, that discriminates between RRR-alpha
      tocopherol and RRR-beta-tocopherol and initiates a cascade of events at the level
      of cell signal transduction leading to cell proliferation inhibition.

PMID- 17180059
TI  - Protection of hepatocytes from Fas-mediated apoptosis by a non-transforming SV40
      T-antigen mutant.
AB  - Apoptosis is crucial for the normal development of multicellular organisms and is
      also important for clearing injured cells, such as virus-infected cells or cancer
      cells. Defective regulation of apoptosis may contribute to viral pathogenesis and
      aetiology of cancer. Apoptosis of injured cells is principally triggered by the
      immune system through cytokines such as Fas-ligand and TNF-alpha. Thus, one of
      the functions of a viral oncogene, such as SV40T-antigen, may be to inhibit
      cytokine-mediated apoptosis. We previously demonstrated that Fas-mediated
      apoptosis of hepatocytes is blocked by the wild-type SV40T-antigen during
      hepatocarcinogenesis. We determined whether this inhibition was directly related
      to the T-antigen or whether it is a secondary event of cell transformation, by
      generating transgenic mice expressing a non-transforming T-antigen mutant able to
      bind endogenous p53 in the liver. This T-antigen mutant cannot induce
      hepatocarcinoma, unlike the wild-type T-antigen. However, like the wild-type T
      antigen, the mutant was a potent inhibitor of apoptosis induced by the Fas
      receptor, but not by the TNF-receptor. Therefore, SV40T-antigen has a new
      property; the inhibition of Fas-mediated apoptosis, which could facilitate the
      emergence of transformed hepatocytes, but is not sufficient to induce it.

PMID- 17180060
TI  - Spontaneous apoptosis in a rat hepatoma cell line and its inhibition by
      dexamethasone.
AB  - Cultures of dedifferentiated rat hepatoma Rab1-5-1 cells exhibit spontaneously a
      high level of mortality during the exponential growth phase. We demonstrate that
      these cells die by apoptosis, showing chromatin condensation and internucleosomal
      DNA fragmentation. Cells of the original H4II cell line and of its differentiated
      and dedifferentiated derivatives also die by apoptosis, but only in heavily
      confluent cultures. We evaluated mortality with time in Rab1-5-1 cultures by
      establishing growth curves, including quantification of floating cells, and
      conclude that up to half of the cells in a culture are lost to apoptosis. The
      production of apoptotic cells is abolished by the presence of 10(-6) M
      dexamethasone and this inhibition is reversible in 48 hours. Rab1-5-1 cells that
      spontaneously die by apoptosis with high frequency represent a novel model to
      investigate factors that regulate the spontaneous frequency of death, and to
      study the nature and the kinetics of commitment to the apoptotic pathway.

PMID- 17180061
TI  - Prevention of apoptosis in CNTF-dependent neurons by a mutant ICE and by viral
      protein CrmA but not by proto-oncogene product Bcl-2.
AB  - The interleukin-1beta converting enzyme (ICE) gene family, (homologues of C.
      elegans cell death gene product Ced-3) plays an important role in controlling
      programmed cell death. Nerve growth factor (NGF) promotes survival of cultured
      embryonic chicken dorsal root ganglion neurons. Ciliary ganglion neurons depend
      exclusively on ciliary neurotrophic factor (CNTF) for survival. Complete
      depletion of NGF or CNTF from culture medium induces apoptosis in both types of
      neurons. We can prevent apoptosis, due either to NGF or CNTF withdrawal and in
      either type of neuron, by overexpression of a mutant inactive ICE and an ICE
      inhibitor, the product of cowpox virus gene crmA. Bcl-2 does not prevent
      apoptosis in CNTF-dependent ciliary neurons or DRG neurons as it does in NGF
      dependent neurons. These results suggest that neuronal cell death is mediated
      through a common effector mechanism involving the Ice family of genes, whereas
      different suppression mechanisms are engaged depending upon the specific
      neurotrophic factors present.

PMID- 17180062
TI  - The ability of Bcl-x(L) and Bcl-2 to prevent apoptosis can be differentially
      regulated.
AB  - Although expression of Bcl-2 has been shown to prevent apoptosis under many
      circumstances, there are several systems in which Bcl-2 fails to promote cell
      survival. We have previously reported that Bcl-2 and Bcl-x(L) display
      differential ability to protect WEHI-231 cells from multiple inducers of
      apoptosis. A possible explanation for this paradox was provided by the discovery
      of Bax. Bax is a Bcl-2-related protein which can inhibit the ability of Bcl-2 to
      enhance the survival of growth factor-dependent cell lines in the absence of
      growth factor. Consistent with the possibility that Bcl-2 function in WEHI-231
      cells is inhibited by Bax, WEHI-231 cells were found to express a high level of
      Bax. To directly test the effects of Bax expression on Bcl-x(L) function, FL5.12
      cells were transfected with both genes. Although Bax overexpression can inhibit
      Bcl-2 from prolonging cell survival upon growth factor withdrawal, Bax
      overexpression did not inhibit Bcl-x(L) from preventing apoptosis in this cell
      line. Although Bcl-2 and Bcl-x(L) were both found to be able to form heterodimers
      with Bax, the majority of Bax in both cases was not complexed to a partner. Our
      data suggest that Bcl-x(L) does not function by simply preventing the formation
      of Bax homodimers which promote cell death. Instead Bax appears to display
      selectivity in its ability to inhibit Bcl-2 but not Bcl-x(L) from prolonging
      survival. Furthermore, our data suggest that the abilities of Bcl-2 and Bcl-x(L)
      to promote cell survival are not identical and can be independently regulated
      within a cell. Regulation of a cell's apoptotic threshold is likely to result
      from a complex set of interactions among Bcl-2 family members and other, as yet
      uncharacterised, regulators of apoptosis.

PMID- 17180063
TI  - The role of Sertoli cells in the differentiation and exclusion of rat testicular
      germ cells in primary culture.
AB  - We have previously established a primary co-culture of spermatogenic and somatic
      cells of the rat testis, in which spermatogenic cells differentiate to some
      extent in terms of the occurrence of testis-specific gene expression. In the
      present study, the interaction between spermatogenic and somatic Sertoli cells
      was investigated in this culture system. Spermatogenic differentiation did not
      proceed when these two cell types were placed on opposite sides of a permeable
      membrane, thus avoiding direct contact. Further, a significant proportion of
      spermatogenic cells died by apoptosis during culture, and Sertoli cells engulfed
      and digested the degenerating spermatogenic cells. These results indicate that
      Sertoli cells participate both in the differentiation of spermatogenic cells and
      in the exclusion of degenerating spermatogenic cells, by directly attaching to
      those cells.

PMID- 17180064
TI  - Intestinal cell apoptosis and Bcl-2 expression.
AB  - Programmed cell death (apoptosis) is a normal characteristic of cells with a
      limited life span like the enterocyte and the usual mode of death for
      proliferative crypt cells subjected to radiation or chemotherapy. The Bcl-2 proto
      oncogene is considered a major regulator of apoptosis. We investigated the
      relationship of enterocyte apoptosis and Bcl-2 expression in rat intestine and
      tissue culture cells. Fragmentation of DNA and levels of Bcl-2 transcripts were
      evaluated in rat enterocyte fractions of the crypt-to-villus axis of
      differentiation and in IEC tissue culture cells. A low percentage of isolated
      nuclei from each enterocyte fraction showed features of DNA fragmentation,
      including crypt cells. Detectable DNA fragmentation was seen in IEC cells only
      when cells were subjected to long-term confluent culture conditions. Bcl-2 mRNA
      was not detected in isolated rat intestinal cells but was detected in IEC cells
      where its level increased with serum deprivation and long-term culture. We
      conclude that increased Bcl-2 expression may be important in rescue of
      proliferative enterocytes subjected to stress.

PMID- 17180066
TI  - Differentiation and delayed cell death in embryonal stem cells exposed to low
      doses of ionising radiation.
AB  - Embryonal stem cells have been used to study the effects of environmentally
      relevant doses of radiation on cell death and differentation. The ES cells were
      found to have a greater than 60% chance of surviving the traversal of a single
      alpha-particle, the lowest possible dose of high linear energy transfer radiation
      a cell may receive. The ES cells appeared to possess the cell cycle checkpoints
      believed to prevent the transmission of the radiation damage. However, delayed
      effects were observed in the progeny. An increased incidence of apoptosis and
      haempoietic differentiation capacity was found to persist in the ES cell
      population over many cell divisions. Since both cell death and differentiation
      are known to play a key role in tissue kinetics, an ES cell model will provide a
      valuable and versatile cell system for studying the role of cell death and
      differentiation in the pathology of radiogenic diseases.

PMID- 17180065
TI  - Nuclear pore clustering is a consistent feature of apoptosis in vitro.
AB  - Two cell lines which show different patterns of DNA fragmentation have been
      examined for variations of their nuclear morphology during apoptosis. FDCP-Mix, a
      pluripotent murine haemopoietic stem cell line which undergoes typical
      internucleosomal cleavage of DNA when induced to apoptosis either by drugs or
      withdrawal of growth factor (IL-3) was compared with the human lymphoid leukemia
      cell line MOLT-4, a cell line which undergoes apoptosis without production of a
      typical DNA 'ladder'. The nuclear morphology of FDCP-Mix cells was consistent
      after apoptotic induction by drug or by growth factor withdrawal. Apoptotic
      nuclear morphology for MOLT-4 and FDCP-Mix showed variations in the distribution,
      density and texture of the electron dense nuclear marginations. Despite these
      differences, clustering of nuclear pore complexes (NPCs) after treatment with the
      topoisomerase II inhibitor etoposide was a common phenomenon for both cell lines.
      Moreover, pore clustering for FDCP-Mix nuclei occurred independently from the way
      in which apoptosis was induced, either by growth factor withdrawal or etoposide
      treatment. In a novel approach, we visualised the clustering of NPCs three
      dimensionally by field emission in-lens scanning electron microscopy (FEISEM).

PMID- 17180068
TI  - Meeting report: the first gordon conference on cell death.

PMID- 17180067
TI  - BCL-2 suppresses ceramide-induced cell killing.

PMID- 17180069
TI  - The faces of death.

PMID- 17180070
TI  - Cell death: programmed, apoptosis, necrosis, or other?
AB  - There are at least two major types of active or physiological cell death. The
      most well-known form, apoptosis or Type I, involves early nuclear collapse,
      condensation of chromatin, generation of nucleosomal ladders, and cell
      fragmentation with little or no early alteration of lysosomes. It is most
      commonly seen in cells deriving from highly mitotic lines, and the cells are
      phagocytosed by neighboring cells or infiltrating macrophages. In metamorphosing
      or secretory cells, and under conditions where the majority of cells die, the
      bulk of the cytoplasm is consumed by expansion of the lysosomal system well
      before nuclear collapse is manifest. This form of cell death has been termed Type
      II cell death, and we revert to this terminology. The requirement for protein
      synthesis is more characteristic of Type II cell death in developmental
      situations than it is for Type I cell death. The variations seen force a
      reassessment of those aspects of physiological cell death that are truly
      universal, thereby focusing attention on the biology of the process. A better
      understanding of the biology and morphology of dying cells will help clarify the
      significance of the molecular and biochemical findings.

PMID- 17180071
TI  - Degradation of chromatin in apoptotic cells.
AB  - We present here a model for the degradation of chromatin in cells undergoing
      apoptosis. This model rationalises all aspects of the fragmentation process that
      have been described to date, explaining not only the patterns of degradation seen
      within individual cells, but also the variability in extent of degradation seen
      in different cells. Although DNA fragmentation in apoptosis was initially
      considered to be solely internucleosomal, it is now apparent that the process is
      much more complex and most, if not all, cells also produce much larger DNA
      fragments. However, in the same way that internucleosomal DNA fragmentation is a
      reflection of chromatin structure, the generation of these larger fragments is a
      reflection of chromatin structure, too. By comparing the ionic requirements for
      the complete pattern of chromatin degradation in nuclei with those required for
      apoptosis, it is apparent that the whole process may be catalysed by two pools of
      Mg-activated?Ca-modulated DNase I-like enzyme activities.

PMID- 17180072
TI  - A role for Grb2 in apoptosis?
AB  - Src homology type 2 (SH2) and type 3 (SH3) domains appear to have an important
      role in signal transduction pathways initiated by tyrosine kinases. SH2 domains
      allow proteins with signalling functions to interact with tyrosine kinases and
      tyrosine-phosphorylated proteins at the plasma membrane, whereas SH3 domains
      allow a distinct type of interaction through binding to proline-rich sequences.
      The adaptor protein Grb2 consists of one SH2 domain and two SH3 domains and
      connects tyrosine kinase receptors to activation of the Ras pathway. Its closely
      related counterpart, Grb3-3, thought to arise by alternative splicing of Grb2
      transcripts, lacks a functional SH2 domain but retains functional SH3 domains. We
      recently presented evidence that Grb3-3 might deliver specific signals causing
      cells to undergo apoptosis. This review will document the mechanism of Grb3-3
      function and discuss its putative involvement in several pathologies. It also
      further strengthens the notion that cells may use alternative splicing as a means
      to drive either a proliferative or a suicidal program.

PMID- 17180073
TI  - Isolation of cell death-associated cDNAs from involuting mouse mammary
      epithelium.
AB  - Although apoptosis is important in determining cell fate and maintaining tissue
      homeostasis, the initiation and control of apoptotic cell death in epithelium is
      not well understood. Post-lactationai involution of the mammary gland provides
      both an important developmental process and a normal physiological setting for
      studying apoptosis of epithelium. We used a differential screening strategy,
      based on previous studies correlating morphology with gene expression and nucleic
      acid integrity during mammary gland involution, to isolate genes involved in the
      regulation and execution of apoptotic cell death in regressing mammary
      epithelium. This screening strategy yielded a large number of genes the
      expression of which is significantly altered during mammary gland involution.
      These include genes associated with cell death processes, tissue remodelling and
      mesenchymal differentiation. In addition, a number of novel genes have been
      isolated. We have used Northern analysis and in situ hybridisation to study the
      expression of a selection of these putative death-associated genes during post
      lactational mouse mammary gland involution.

PMID- 17180074
TI  - s-Myc acts as a transcriptional activator and its sequence-specific DNA binding
      is required for induction of programmed cell death in glioma cells.
AB  - We previously reported that s-Myc expression effectively induces programmed cell
      death (PCD) by apoptosis in glioma cells that express only mutated p53. To
      determine the molecular mechanism of s-Myc-induced PCD, we examined the
      correlation between transcriptional activation of s-Myc and its ability to induce
      PCD. Using a reporter plasmid having an upstream promoter region containing four
      repeats of the hexanucleotide CACGTG, we found that s-Myc can activate
      transcription of a reporter gene from this plasmid. Two mutated forms of s-Myc
      protein, s-MycCKII and s-MycmBR, were created. While s-MycCKII whose casein
      kinase (CK) II cognate sequence was restored in the internal acidic domain
      activated transcription as efficiently as wild-type s-Myc and induced PCD in
      glioma cells, s-MycmBR having a mutated basic region unable to bind the CACGTG
      motif did not. These findings suggest that transactivation activity of s-Myc
      through sequence-specific DNA binding may be indispensable for induction of PCD
      but that lack of a CK-II cognate sequence in the internal acidic domain may have
      little effect on these functions of s-Myc.

PMID- 17180075
TI  - Primary cultured murine hepatocytes but not hepatoma cells regulate the cell
      number through density-dependent cell death.
AB  - The mechanisms by which hepatocytes regulate their cell numbers in culture have
      been examined. We found that when murine hepatocytes were cultured at an
      overconfluent stage, the number of viable cells were reduced to that of the
      confluent stage 48 h later by cell death. Cell death was accompanied by LDH
      release, and it was observed only in primary cultured hepatocytes but not in
      hepatoma cells. Genomic DNA analysis using electrophoresis showed that DNA
      fragmentation, a biochemical hallmark of apoptosis, was induced in superconfluent
      cultures of hepatocytes in a cell-density-dependent fashion, but not in pre
      confluent cells. DNA fragmentation was rapidly induced 2 h after the beginning of
      the in vitro culture and continued up to 24 h later. Flow cytometry analysis
      demonstrated that the nuclei from the hepatocytes in a high density culture were
      condensed and that the DNA content was reduced. These data suggest that the
      mechanism of cell death is apoptosis. The DNA fragmentation seen in the high
      density hepatocyte culture was not observed in hepatoma cell lines. Moreover,
      apoptosis was induced in hepatocytes of MRL/lpr mice, suggesting that the Fas
      antigen was not involved in the apoptotic process. Apoptosis was inhibited by a
      protein synthesis inhibitor, cycloheximide, and by a calmodulin antagonist, W-7.
      Taken together, the results indicate that high density culture of murine
      hepatocytes though not hepatoma cells regulate their cell numbers by an apoptotic
      mechanism. The apoptosis is dependent on de novo protein synthesis and
      intracellular calcium metabolism.

PMID- 17180076
TI  - Pathways of tumour cell killing by activated macrophages: both tumour cell
      membrane and nucleus can be the primary target.
AB  - Plasma membrane and nucleus can be primary targets of tumour cell killing by
      activated macrophages (AMo). Necrotic-type cytotoxicity with loss of membrane
      integrity and cytoplasmic swelling was expressed by AMo from normal and from
      perforin-deficient mice, indicating that perforin was not involved. Incubation
      with AMo consistently triggered the release of thymidine from prelabelled
      targets, whereas chromatin condensation and small DNA fragments were only
      occasionally detected. It is shown by means of Pulsed-Field Gel Electrophoresis
      that DNA degradation in target cells is a slowly progressing process that may
      stop at any time, indicating that nuclear-type killing doesnot necessarily lead
      to the formation of low molecular weight fragments. Neither Fas nor the p55
      tumour necrosis factor receptor appear to be involved in signalling nuclear-type
      killing. Accordingly, AMo do mediate membrane- and nuclear-type killing but the
      mechanisms differ from those identified in T cell cytotoxicity.

PMID- 17180077
TI  - The CD95(APO-1/Fas) receptor/ligand system: death signals and diseases.

PMID- 17180078
TI  - CD95 (APO-1/Fas)-associating signalling proteins.
AB  - The CD95 (APO-1/Fas) receptor has attracted great interest in recent years
      because it transduces an apoptotic signal in a variety of different tissues. CD95
      belongs to the NGF/TNF-receptor superfamily, members of which need to be
      trimerized by specific protein ligands in order to generate a signal. This review
      focuses on recent advances in the understanding of the proximal signal
      transduction mechanism of CD95. The cloning of numerous proteins that interact
      with CD95 and other members of this receptor family and the in vivo
      identification of several proteins that associate with CD95 in a ligand-dependent
      fashion opens the way to delineate the death pathway and to explain crosstalk
      among these receptors on a molecular basis.

PMID- 17180079
TI  - Fas-mediated apoptosis and sphingomyelinase signal transduction: the role of
      ceramide as a second messenger for apoptosis.
AB  - In this article, we review the role of sphingomyelinases and ceramide in the Fas
      mediated apoptosis signal transduction cascade. Several stimuli, including
      ligation of Fas, have been shown to enhance either neutral and/or acidic
      sphingomyelinase activity and increase ceramide content in intact cells or cell
      membrane preparations. Ceramide seems to have different functions, including
      induction of apoptosis, growth arrest, and/or differentiation, depending on cell
      type or location of sphingomyelin hydrolysis within the cell. Several putative
      targets for ceramide activity, including a kinase and a phosphatase, have also
      been identified. While ceramide and acidic sphingomyelinase activity appear to be
      involved in apoptotic signalling for Fas and other members of the tumour necrosis
      factor receptor family, it is clear that other signals and mechanisms are
      necessary for Fas-mediated apoptosis.

PMID- 17180080
TI  - Role of ICE-related and other proteases in Fas-mediated apoptosis.
AB  - Interleukin-1beta-converting enzyme (ICE)-like proteases comprise a novel family
      of unusual cysteine proteases which have been implicated in programmed cell death
      in both invertebrates and mammals. Current available evidence indicates a role of
      ICE proteases as central executioners of apoptosis triggered by the cell surface
      receptor Fas (APO-l). The presence of multiple mammalian ICE proteases with
      partially overlapping but distinct activities suggests a complex proteolytic
      cascade which is induced upon Fas ligation. The precise role of single members of
      the ICE family in Fas-mediated apoptosis, however, is still unclear. Here, we
      summarize the present knowledge about the relevance of ICE proteases, their
      potential targets, and interaction with unrelated proteases in cell death
      mediated by Fas and other apoptotic stimuli.

PMID- 17180081
TI  - Disturbances of the CD95 (APO-1/Fas) system in disorders of lymphohaematopoietic
      cells.
AB  - Control of tissue homeostasis is maintained through programs that balance
      proliferation and cell death. Physiologic cell death is primarily mediated
      through apoptosis. Deregulations of the cellular programs and genes that
      determine apoptosis have recently been considered to be involved in a variety of
      human diseases. One of the central regulatory systems for apoptosis is the CD95
      (APO-1/Fas) system. Defects in the CD95 cell surface receptor and deregulated
      expression of CD95 and the CD95 ligand have been shown to be involved in diseases
      such as lymphoproliferation, AIDS and haematopoietic failure. This review
      summarizes our current knowledge on the implication of the CD95 system especially
      in lymphohaematopoietic diseases in humans.

PMID- 17180082
TI  - The influence of calcium and reactive oxygen species on influenza virus-induced
      apoptosis.
AB  - In previous studies we observed that influenza A and B viruses induce apoptosis
      in Madin-Darby canine kidney (MDCK) cells and that this apoptosis is blocked by
      expression of bcl-2. Using a well-characterized, highly virulent, avian influenza
      virus, A/Turkey/Ontario/7732/66 (H5N9) (Ty/Ont), we sought to better understand
      this system. We investigated the influence of two cellular factors that are known
      to function in other models of apoptosis inhibited by bcl-2, calcium (Ca(2+)) and
      reactive oxygen species (ROS). Although Ca(2+) chelators generally inhibit
      apoptosis, treatment of MDCK cells with either an extracellular chelator, EGTA,
      or an intracellular chelator, BAPTAAM, induced apoptosis instead and enhanced
      Ty/Ont-induced apoptosis. Conversely, treatment with an ionophore, ionomycin,
      blocked the viral-induced apoptosis. In terms of ROS, neither treatment with
      antioxidants, N(2) flushing to induce hypoxia, nor nigericin (a compound which,
      like bcl-2, stabilizes the mitochondrial membrane potential against the effects
      of ROS and subsequent Ca(2+) dysregulation) were able to block Ty/Ont-induced
      apoptosis. Therefore, it is likely that ROS play little, if any, role in
      influenza-induced apoptosis in MDCK cells and the influence of Ca(2+) appears to
      be opposite to that in the majority of other more classical models of apoptosis.

PMID- 17180083
TI  - Isolation, differential splicing and protein expression of a DNase on the human X
      chromosome.
AB  - A systematic search for genes differentially expressed in human tissues resulted
      in the isolation of a gene encoding a protein with high homology to DNase I. In
      addition to the recently described cDNA sequence (Parrish et al., 1995) we have
      isolated a transcript, alternatively spliced in the 5' noncoding region. The gene
      is located between the QM and the XAP-2 gene in Xq28 and encodes a 302 amino acid
      protein with 39% identity to human DNase I. Besides a high homology at the
      nucleotide and amino acid level, most exon-intron boundaries of DNase I and DNase
      X are identical, indicating that both genes may have evolved from a common
      ancestor. The predicted function was verified by expression of a recombinant
      protein in an inducible bacterial system and detection of DNase activity. In
      contrast to DNase I a 18 kdal amino terminal fragment of the full length 35 kdal
      protein exhibited DNase activity.

PMID- 17180084
TI  - Decreased antioxidant defence and increased oxidant stress during dexamethasone
      induced apoptosis: bcl-2 prevents the loss of antioxidant enzyme activity.
AB  - When the WEHI7.2 mouse lymphoid cell line was treated with dexamethasone to
      induce apoptosis the activities and transcript levels of the antioxidant defence
      enzymes catalase, superoxide dismutase (SOD) and DT-diaphorase exhibited a
      progressive decrease over 48 hours. Catalase activity was maintained and total
      SOD and DT-diaphorase activity showed smaller decreases following dexamethasone
      treatment of WEHI7.2 cells transfected with the bcl-2 oncogene, which protects
      the cells against apoptosis. Treatment of wild-type WEHI7.2 and bcl-2 transfected
      cells with a catalase inhibitor, aminotriazole, was not sufficient to induce
      apoptosis. Antioxidants, including bovine liver catalase, bovine erythrocyte CuZn
      SOD, sodium selenite and Trolox, a water soluble vitamin E analogue, as well as
      hypoxia, inhibited dexamethasone-induced apoptosis. These results suggest that
      oxidant stress due to the decreased activity of antioxidant defence enzymes may
      play a role in dexamethasone-mediated lymphoid cell apoptosis and that bcl-2 may
      prevent apoptosis by maintaining the level of critical antioxidant defence
      mechanisms, which include catalase.

PMID- 17180085
TI  - Over-expression of Bcl-2 protects against apoptosis induced by the bioreductive
      cytotoxic drug SR4233 (Tirapazamine).
AB  - The human B-cell lymphoma cell line PW undergoes radiation-induced programmed
      cell death (PCD). Bcl-2 transfected PW cells, that overexpressed Bcl-2, were
      significantly more radioresistant than parental or neomycin control transfected
      PW cells. The viability of Bcl-2 transfected cells was significantly greater than
      that of parental PW cells treated with the bioreductive cytotoxin SR4233 under
      aerobic conditions. Bcl-2 transfectants were also significantly more resistant to
      hypoxia-induced PCD. However, there was no significant difference in the
      viability of parental and Bcl-2 transfected cells exposed to SR4233 under hypoxic
      conditions (pO(2)<100 ppm). Incubation of parental PW cells with N-acetyl
      cysteine decreased the cytotoxicity of SR4233 under aerobic but not anaerobic
      conditions. Depletion of cellular glutathione with buthionine sulphoxamine killed
      nearly 100% of control PW cells, but none of the Bcl-2 transfectants under the
      same conditions. The TBARS assay for lipid peroxidation showed that Bcl-2
      transfectants had a significantly lower level of lipid peroxidation than parental
      PW cells following a 24 hour constant exposure to SR4233 under aerobic
      conditions. These results suggest that Bcl-2 overexpression inhibits PCD induced
      by the bioreductive cytotoxin SR4233 under aerobic conditions as well as PCD
      induced by hypoxia, and that there are other pathways leading to PCD that are
      unaffected by Bcl-2 overexpression.

PMID- 17180086
TI  - Lovastatin induces apoptosis in a metastatic ovarian tumour cell line.
AB  - Lovastatin is a very specific and potent inhibitor of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase, which regulates a rate-limiting step in the
      cellular synthesis of isoprenoid and cholesterol. In this study, we demonstrate
      that treatment of rat ovarian metastatic OV1N cells with lovastatin induces
      apoptosis. Furthermore, apoptotic death of lovastatin-treated OV1N cells can be
      prevented by the addition of either mevalonic acid (an immediate metabolite of
      HMG-CoA) or farnesyl pyrophosphate (one of the downstream products of mevalonic
      acid metabolism). However, metabolic derivatives of farnesyl pyrophosphate failed
      to prevent the apoptotic effect of lovastatin on cells. Therefore farnesyl
      pyrophosphate appears to be important for cell survival and the relationship of
      this compound to protein farnesylation and apoptosis induction is discussed.

PMID- 17180087
TI  - Apoptosis in procyclic Trypanosoma brucei rhodesiense in vitro.
AB  - Apoptosis is a phenomenon previously associated exclusively with metazoan
      organisms. We show here that procyclic insect form Trypanosoma brucei
      rhodesiense, a protozoan parasite, when treated in vitro with concanavalin A
      displayed several features normally associated with apoptosis in metazoan cells.
      Lectin treatment induced cleavage of nuclear DNA into oligonucleosomal fragments,
      suggesting activation of an endogenous nuclease in the parasite. Treated
      trypanosomes, although agglutinated and non-motile, exhibited fluorescence after
      treatment with the vital stain fluorescein diacetate and retained (3)H-uridine
      indicating that their cell membranes remained intact during the period of DNA
      fragmentation. Electron micrographs showed characteristic morphology of cells
      undergoing apoptosis, including surface membrane vesiculation and migration of
      chromatin to the periphery of the nuclear membrane while mitochondria remained
      intact. These results suggest that treatment with concanavalin A triggers a cell
      death mechanism in T. b. rhodesiense similar to the process of apoptosis
      described in metazoa.

PMID- 17180089
TI  - Obituary: chiara d'onofrio (1953 - 1996).

PMID- 17180088
TI  - Chromatin isolated from viable human PBLs contains DNA fragmented to >/=50 kb.
AB  - Massive chromatin fragmentation (around 50 kb, to several hundred kb) is observed
      in nuclear lysates of human peripheral blood lymphocytes (PBLs) upon their
      treatment with nuclease-free protein-denaturants. There is a consistent variation
      in the fragment size distributions that parallels the proliferative activity of
      the cells. Predominantly approximately 50 kb fragmentation is exhibited in
      samples from cells immunsuppressed via CD4 crosslinking, as opposed to the
      heterogeneous, higher molecular weight DNA of anti-TcR/CD3-, phytohemagglutininor
      concanavalin A-stimulated cells. Tritiated thymidine incorporated into DNA in the
      latter cultures can be detected in the approximately 50 kb band. Direct lysis of
      agarose-embedded, live cells in alkali+detergent also yields fragmented DNA, with
      a single-strand size of >/=50 kb. These data suggest that (i) the cells yielding
      fragmented DNA were alive at the time of DNA extraction, (ii) either regularly
      arranged, preformed nicks or hypersensitive sites may be present at every roughly
      50-100 kb in the chromatin of PBLs, (iii) these sites or the fragmentation
      mechanism acting upon them, appear to be regulated in concert with the transit of
      cells between the resting and proliferative compartments.

PMID- 17180090
TI  - Meeting Report: Recent advances in apoptosis: a report on The Third
      Euroconference on Apoptosis.

PMID- 17180091
TI  - Educational Corner: Activation-induced T cell death.

PMID- 17180092
TI  - Educational Corner: Ceramide-mediated pathways in FAS/APO-1 signalling.

PMID- 17180093
TI  - Proteases in apoptosis.

PMID- 17180094
TI  - The ICE family of cysteine proteases as effectors of cell death.
AB  - Programmed cellular suicide follows a set of distinct morphological events
      involving profound cytoplasmic and nuclear changes. The recent discovery of a
      family of mammalian homologues of the Caenorhabditis elegans cell death protein
      CED-3 is now providing insight into how these events might be brought about.
      These mammalian proteins encode cysteine proteases with homology to the
      interleukin-1beta converting enzyme (ICE). CED-3 and seven of its currently known
      mammalian homologues cleave their substrates after an aspartate residue, a
      property shared only by the cytotoxic T cell (CTL) protease granzyme B which is
      necessary for the CTL-mediated killing of target cells. A number of proteins
      previously known to be cleaved in cells undergoing apoptosis have now been shown
      to be targeted by ICE-like proteases. Although many questions remain, it is
      becoming increasingly clear that this unique group of proteases play a central
      effector role in the process of physiological cell death. This article reviews
      various aspects of the ICE family of proteases.

PMID- 17180095
TI  - Activation of apoptosis pathways by granzyme B.
AB  - Cytotoxic lymphocytes induce apoptosis of target cells by degranulating and
      releasing the serine protease granzyme B and the pore forming protein perforin.
      Granzyme B is an aspartic acid protease similar to members of the interleukin
      1beta converting enzyme (ICE) family. We review the evidence for the
      participation members of the ICE family of proteases and cdc2 kinase in granzyme
      B-induced apoptosis.

PMID- 17180096
TI  - Calpain and cell death.
AB  - Neither the early nor the late steps in apoptosis have been defined
      biochemically. Several different signalling pathways have been implicated, and
      these are familiar from other signalling paradigms. In what way could they lead
      to cell death, when under the usual conditions they are involved in reversible
      activation events? A possible role for proteolysis is suggested, because the
      cleavage of a peptide bond is one of the few irreversible processes in cellular
      metabolism, and death, after all, is an irreversible outcome. In this review we
      discuss the calcium-dependent neutral protease calpain, a member of the papain
      family of cysteine proteases quite distinct from the ICE family. Calpain has been
      shown to play an essential role in several important examples of physiologic
      apoptosis. It seems to play its part after the various 'private' pathways have
      been invoked, but before the final common pathway.

PMID- 17180097
TI  - Inactivation of retinoblastoma gene product RB or an RB-related protein by SV40 T
      antigen in MDCK epithelial cells results in massive apoptosis.
AB  - SV40 T antigen (LT) transformation of renal MDCK epithelial cells resulted in
      massive apoptosis in the presence of serum. Cell death was dependent on the
      ability of LT to bind RB or a related protein, since MDCK cells expressing LT
      mutants unable to bind RB did not die. Apoptosis could be rescued by treatment of
      cells with EGF and TPA, a property linked to their ability to promote cell
      growth. Our results indicate an inverse correlation between proliferation and
      apoptosis. Thus LT transformation induced survival-factor dependence in
      epithelial cells, in contrast to its effect in fibroblasts. RB inactivation also
      resulted in a strong down-regulation of c-myc and c-fos, which were previously
      found to be highly and constitutively expressed in epithelial cells. RB gene
      transfer in MDCK(LT) cells restored cell viability and high c-myc expression. C
      myc gene transfer in these cells also resulted in a significant survival effect.
      These results suggest that RB anti-cell death activity is at least partly
      mediated by up-regulation of c-myc. Overexpression of Bcl2 also protected cells
      against apoptosis. The role of RB and c-myc in cell survival is discussed and
      related to maintenance of the differentiation state rather than to their
      properties in cell cycle progression.

PMID- 17180098
TI  - Monitoring of CD95 (APO-1/Fas) ligand expression in human T cells by quantitative
      RT-PCR.
AB  - CD95 (APO-1/Fas) receptor/ligand interaction is a key regulatory pathway for
      apoptosis in lymphoid cells. We developed a quantitative RT-PCR for the human
      CD95-L to determine expression levels in lymphoid cell lines and in lymphocytes
      derived from blood of healthy individuals. In untreated peripheral blood T
      lymphocytes and T cell lines constitutive expression of the CD95-L mRNA was found
      at low levels. Stimulation of T cells by treatment with PMA and ionomycine (P/I)
      lead up to a 100-fold maximal increase in CD95-L mRNA after 4 h. CD95-L mRNA is
      produced by activated CD8 and CD4T cells. In vivo increased CD95-L mRNA
      expression was found in freshly isolated T cells during the acute phase of EBV
      infection. In contrast to T cells, CD95-L mRNA could be induced in some B lineage
      cell lines only after five days of stimulation. Since defective or accelerated
      CD95/CD95-L interaction is considered to be involved in the pathogenesis of
      lymphoproliferation, autoimmunity and AIDS, the quantitative RT-PCR assay
      described in this paper may provide a powerful tool for monitoring CD95-L
      expression in these diseases.

PMID- 17180099
TI  - Concanavalin A-induced apoptosis in murine macrophages through a Ca(2+)-
      independent pathway.
AB  - Concanavalin A (ConA), normally a mitogen of T lymphocytes, was found to induce
      apoptosis or programmed cell death in murine peritoneal macrophages. The
      following observations support this assertion: 1) incubation of peritoneal
      macrophages or cultured PU5-1.8 macrophage cells with ConA caused a dose- and
      time-dependent reduction of mitochondrial dehy-drogenase activity as measured by
      3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, 2)
      treatment of cells with ConA induced formation of apoptotic bodies as seen under
      the confocal laser scanning microscope, 3) challenge of cells with ConA produced
      a considerable amount of cell debris with DNA content next to G0 phase as
      revealed by flow cytometry and 4) ConA was able to elicit DNA fragmentation in
      these cells. The involvement of Ca(2+) in mediating the apoptosis was studied in
      single cells by confocal laser scanning microscope using the Ca(2+) fluorescence
      dye, fluo-3. Our results show that ConA induced an immediate rise of
      intracellular free Ca(2+) concentration as well as opening of Ca(2+) channels on
      cell surface. But when the cells were treated with 1,2-bis(o-aminophenoxy) ethane
      N, N, N', N'-tetraacetic acid/AM (BAPTA/AM), a Ca(2+) chelator, to buffer the
      rise of internal Ca(2+), ConA still caused DNA fragmentation. Furthermore,
      injection of Ca(2+) into the cell with ionomycin had no stimulatory effect on DNA
      fragmentation. These results suggest that Ca(2+) changes induced by ConA are not
      a prerequisite for apoptosis in macrophages.

PMID- 17180100
TI  - Expression of p53, bcl-2, bax, bcl-x2 and c-myc in radiation-induced apoptosis in
      Burkitt's lymphoma cells.
AB  - Apoptosis, a form of physiological cell death, is a genetically determined
      program essential for normal development and maintenance of tissues, which has
      been linked to a variety of gene products. We have examined the susceptibility to
      radiation-induced apoptosis of cell lines derived from the human B cell tumour,
      Burkitt's lymphoma (BL), displaying a variety of phenotypic characteristics and
      expressing genes implicated in apoptosis at different levels. The susceptibility
      to apoptosis following gamma radiation varied significantly amongst the lines.
      Cell lines with wild type p53 were susceptible to radiation-induced apoptosis but
      two of five BL lines with only mutant p53 allele also displayed similar
      susceptibility. Some BL cell lines that expressed bcl-2 at levels comparable with
      Epstein-Barr virus (EBV) transformed normal B cells were highly susceptible to
      gamma radiation-induced apoptosis, whereas others expressing low levels were
      resistant. When these lines were analysed for bax and bcl-X(L) expression again
      no correlation was observed with susceptibility or resistance to apoptosis. Two
      BL cell lines having deregulated expression of c-myc were resistant to the
      induction of apoptosis while two others which had regulated c-myc expression were
      susceptible. Thus the status of p53, c-myc, bcl-2, bcl-X(L) and bax is not
      sufficiently informative in BL lines to predict susceptibility to radiation
      induced apoptosis.

PMID- 17180101
TI  - Apparent inhibition of apoptosis by polyamines and aminothiols in DNA
      fragmentation assays is artifactual.
AB  - We report that, in commonly used DNA fragmentation assays, polyamines and the
      radioprotective aminothiol WR1065 artifactually depress the degree of spontaneous
      or induced cellular apoptosis in two distinct ways. Firstly, in assays utilizing
      Hoechst 33258 dye to measure apoptotic DNA, both amines quench the fluorescence
      of low affinity dye/DNA binding resulting in preferential underestimation of DNA
      in the apoptotic DNA fraction and a resultant underestimation of the extent of
      DNA fragmentation. Secondly, these amines can cause aggregation and condensation
      of apoptotic DNA, causing anomalous sedimentation under conditions universally
      employed to separate apoptotic from intact DNA in cell lysates. This anomalous
      sedimentation of apoptotic DNA leads to underestimation of fragmentation in
      fluorescence assays as well as in agarose gel assays. We demonstrate that
      manipulation of the ionic strength of the lysis buffer or lowering the dye
      concentration ameliorates the effects of dye quenching in the Hoechst assay.
      Alternatively, this effect is alleviated by substituting DAPI for Hoechst in this
      assay. Inclusion of a polyanion to the lysis buffer antagonizes the condensation
      and anomalous sedimentation of apoptotic DNA observed regardless of which dye is
      used in the assay. These studies call into question the validity of previously
      reported studies suggesting that polyamines and the radioprotective aminothiol,
      WR1065, inherently suppress the apoptotic process and underline the need to
      consider alternative endpoints of apoptosis such as morphology in order to assess
      effects on cellular apoptosis of exogenously added agents, particularly di- or
      polycations.

PMID- 17180103
TI  - Educational Corner: The ICE/Ced-3-family proteases as the apoptotic executioner.

PMID- 17180102
TI  - Imidazole antifungals Miconazole and Econazole induce apoptosis in mouse lymphoma
      and human T cell leukemia cells: regulation by Bcl-2 and potential role of
      calcium.
AB  - We have recently reported that thapsigargin (TG), a specific endoplasmic
      reticulum (ER)-associated Ca(2+)-ATPase inhibitor, induces apoptosis in mouse
      lymphoma cells. In view of recent evidence that the imidazole antifungals
      econazole (EC) and miconazole (MC) inhibit TG-sensitive Ca(2+)-ATPase activity in
      normal rat thymocytes, we investigated the effect of these agents on
      intracellular Ca(2+) homeostasis and cell survival in WEHI7.2 mouse lymphoma
      cells and human CEMT-cell leukemia cells. In this report, we demonstrate that MC
      treatment releases Ca(2+) from the TG-sensitive ER pool of WEHI7.2 cells. MC
      induced apoptosis, based on morphological and biochemical criteria, and on
      inhibition by the Bcl-2 oncogene. Moreover, intracellular Ca(2+) changes induced
      by MC treatment were inhibited by overexpression of Bcl-2. In addition to
      inducing cell death in WEHI7.2 cells, MC induced apoptosis in the glucocorticoid
      sensitive and resistant human T-cell leukemia lines, CEM-C7 and CEM-C1
      respectively, in normal thymocytes and in normal lymphocytes. Based on their
      apoptosis-inducing activity, imidazole derivatives should be explored as
      potential immunosuppressive and/or chemotherapeutic agents.

PMID- 17180104
TI  - Eosinophils and skin: a new link on cell death.

PMID- 17180105
TI  - Novel therapeutic strategies via the apoptosis pathways to resolve chronic
      eosinophilic inflammation.
AB  - Physiologic cell death is a necessary process to maintain correct cell numbers.
      Alterations in this process may contribute to the pathogenesis of a number of
      human diseases. During the past few years, evidence has been adduced indicating
      that eosinophilic disorders are associated with a defect in eosinophil apoptosis.
      Here we review our recent progress in understanding the processes regulating
      eosinophil apoptosis, and the implications of these results for novel therapeutic
      possibilities.

PMID- 17180106
TI  - The relationships among adhesion, stratification and differentiation in
      keratinocytes.
AB  - Epidermis is a self-renewing, multilayered tissue composed primarily of
      keratinocytes. The epidermal keratinocyte follows a terminal differentiation
      pathway that under normal circumstances is tightly linked to its position within
      the epidermis and culminates in the formation of the protective barrier (stratum
      corneum) that constitutes the outermost layer of skin. Strong but pliant adhesive
      mechanisms are essential for normal functioning of the epidermis. In the
      epidermis, adhesion is mediated primarily by four structures: hemidesmosomes and
      focal adhesions, which function in cell-matrix adhesion, and desmosomes and
      adherens junctions, which function in cell-cell adhesion. In this review we
      concentrate on the transmembrane components of these structures, which are
      thought to mediate directly the adhesive function. Members of the integrin family
      of adhesion molecules comprise the transmembrane components of hemidesmosomes and
      focal adhesions, although hemidesmosomes also have a second, unrelated
      transmembrane molecule known as 'bullous pemphigoid antigen 2'. Members of the
      cadherin family are the transmembrane constituents of desmosomes and adherens
      junctions. Desmosomes consistently contain two types of cadherins (desmoglein and
      desmocollin), while adherens junctions may contain only one type of cadherin (E-
      or P-cadherin). Expression of most of the transmembrane components varies with
      the position of the keratinocyte within the epidermis and thus may reflect the
      degree of epidermal differentiation. All of the integrin subunits have been
      localized predominantly to the basal layer. In contrast, the cadherins show very
      complex expression patterns throughout the epidermis. Desmogleins and
      desmocollins (the desmosomal cadherins) are each encoded by three genes, and the
      expression of each gene is limited to certain epidermal layers. With respect to
      the cadherins of the adherens junction, it has been shown that E-cadherin is
      present throughout the epidermis, while P-cadherin is limited to the basal layer.
      Interestingly, these complex expression patterns of integrins and cadherins
      within the epidermis may not simply be passive events in differentiation; rather,
      evidence is accumulating that adhesion molecules can exert a dynamic role in
      epidermal differentiation/stratification. For example, decreased adhesion to
      extracellular matrix, induced by changes in one or more integrins, appears to be
      a signal that induces certain differentiation-related events. Even more profound
      effects on epidermal morphogenesis have been demonstrated for the cadherins. E-
      and/or P-cadherin is required not only to initiate normal intercellular junction
      formation but also for the subsequent development of a stratified epithelium.
      Thus, the findings to date with both integrins and cadherins suggest that
      adhesion molecules may function not just as direct mediators of adhesion, but
      also as regulators of epidermal stratification, differentiation, and
      morphogenesis.

PMID- 17180107
TI  - Epidermal keratinocytes - genes and their regulation.
AB  - In recent years, the human epidermal keratinocyte has been extensively studied.
      These studies have shown that epidermal growth factor (EGF), transforming growth
      factor-beta (TGFbeta), retinoids, phorbol ester, vitamin D and other agents
      regulate keratinocyte proliferation, differentiation, apoptosis and gene
      expression. We review progress in understanding the mechanisms that regulate
      keratinocyte structural gene expression. In most cases little is known regarding
      the factors that regulate gene expression in response to a physiological agent.
      However, the available results suggest a role for a variety of transcription
      factors, including STAT factors, NFkappaB, octamer site (OCT) binding proteins
      and activator protein 1 (AP1) factors in regulating expression of these genes.
      Among these transcriptional regulators, AP1 appears to play a central role. We
      review the current literature regarding the regulation of involucrin, loricin,
      transglutaminase type 1 and cytokeratin gene expression. This survey indicates
      that the AP1 family of transcriptional regulators is implicated in the regulation
      of nearly all of these genes. We also discuss recent studies which describe the
      distribution of the AP1 factors, c-jun, junB, junD, Fra-1,Fra-2, c-fos and fosB,
      in epidermis.

PMID- 17180108
TI  - A chance-selection model for cell differentiation.
AB  - A chance-selection model is proposed to explain cell differentiation. It is based
      on the general idea that stochasticity at the molecular level generates diversity
      in cell types whereas cell interactions impose a characteristic order on the
      developing embryo. In this model, gene expression depends on stochastic molecular
      interactions between transcriptional regulators and DNA. Random diffusion of
      these regulators along DNA causes differential gene expression in differentiating
      cells.The role of phosphorylation or dephosphorylation of transcriptional
      regulators, triggered by cell interactions, is to control their random diffusion
      and to stabilize stochastic gene expression in differentiated cells. This model
      is based on well documented phenomena: random diffusion of DNA binding molecules
      along DNA, phosphorylation or dephosphorylation of transcription factors by
      protein kinases or phosphatases and control of DNA binding of transcription
      factors through this latter process. The different explanatory powers of
      deterministic and stochastic models are discussed.

PMID- 17180109
TI  - Small DNA fragments isolated from human T-cell clones are enriched in sequences
      involved in DNA bending.
AB  - IL-2 deprivation induces apoptosis in human IL-2-dependent T-cell clones. This
      process is characterized by typical cell morphology, changes in the cellular
      membranes and fragmentation of chromatin into units of single and multiple
      nucleosomes. We isolated apoptotic DNA of an IL-2-deprived T-cell clone and
      sequenced randomly selected fragments representing single and multiple
      nucleosomes.The frequency of phased adenosine tracts was markedly increased in
      the small apoptotic fragments as compared to oligonucleosomes. Our results thus
      indicate that chromatin fragmentation in human apoptotic T-cells is not random
      but preferentially involves DNA sequences with the capability to form bent DNA.
      Whether this indicates a colocalization of DNase cleavage sites and phased
      adenosine tracts on the chromosomes or a bias in selecting sites for apoptotic
      DNA fragmentation is discussed. Analysing the underlying mechanisms will shed new
      light on DNA degradation in apoptosis.

PMID- 17180110
TI  - Morphometric and functional study of apoptotic cell chromatin.
AB  - Apoptosis is usually characterized by profound morphological nuclear changes.
      Chromatin undergoes a progressive condensation that eventually involves all the
      nucleus. At earlier stages chromatin appears as divided in compact and diffuse
      areas, while the nuclear pores disappear from the nuclear envelope that surrounds
      the compact areas, and cluster around diffuse chromatin. Here we have performed a
      morphometric study on the different chromatin areas of freeze-fractured apoptotic
      cell nuclei in order to investigate its morphometric and functional organization.
      We have found large portions of inactive chromatin aggregations corresponding to
      the dense cap-shaped patches, while domains of nucleosomic fibres have been
      identified in the diffuse chromatin areas. The correlation of the nucleosomic
      fibre/diffuse chromatin domain with the nuclear pore clusters is demonstrated,
      and its implications with a possible residual nuclear activity are discussed.

PMID- 17180112
TI  - Thapsigargin induces mitochondrial dysfunction and apoptosis in the mastocytoma
      P815 cell line and in mouse thymocytes.
AB  - Thapsigargin is a plant-derived inhibitor of the endoplasmic reticulum Ca(2+)
      ATPase.Treatment with thapsigargin leads to a rapid, large and prolonged increase
      in the intracellular calcium ion concentration ([Ca(2+)](i)). Previously
      thapsigargin has been shown to inhibit proliferation and induce apoptosis. Here
      we report the results of thapsigargin treatment in thymocytes harvested from 10
      day-old mice and in the P815 mastocytoma cell line. In thapsigargin-treated cells
      we observed enlarged mitochondria with disrupted cristae structure. These
      mitochondria closely resembled those observed after the induction of phase
      transition. To determine if the mitochondria were functioning normally the cells
      were stained with rhodamine 123 (R123) and analysed with flow cytometry. After
      thapsigargin treatment the R123 staining decreased, indicative of a loss of
      mitochondrial membrane potential. Furthermore intracellular ATP concentrations
      were also found to be reduced in cells treated with thapsigargin. Taken together
      these results indicate an increase in the [Ca(2+)](i) caused by thapsigargin
      treatment results in dysfunctional mitochondria and reduced ATP. We propose that
      this decrease in the concentration of ATP provokes the onset of thapsigargin
      induced apoptosis. To investigate the effect of thapsigargin treatment on the
      cell cycle, rapidly cycling P815 cells were sorted into populations enriched for
      either G(0)/G(1) or S/G(2)/M phases, and these populations were then treated with
      thapsigargin. Thapsigargin treatment induced a cell cycle block before S phase.
      We propose that the block in the cell cycle induced by thapsigargin was a result
      of the decreased intracellular ATP concentration interfering with the energy
      requiring processes of DNA replication. The block could also be related to the
      high intracellular calcium ion concentration that would interfere with the subtle
      calcium transients involved in the cell's preparations for replication and
      mitosis. Apoptosis occurred to an equal extent in both populations of cells.

PMID- 17180111
TI  - Bile acid activation of the gadd153 promoter and of p53-independent apoptosis:
      relevance to colon cancer.
AB  - Bile acids are strongly implicated in the etiology of colon cancer. Bile acids
      also induce apoptosis, and this action may be a key to understanding their role
      in colon cancer. However the mechanism of bile acid induction of apoptosis is not
      known. We present evidence of bile acid activation of the gadd153 promoter (a
      promoter activated by DNA damaging agents). We also show that bile acid induction
      of apoptosis is p53-independent. In addition, bile salts were found to induce
      blebbing preceding the actual morphological onset of apoptosis, which indicates
      early cytoskeletal alterations.

PMID- 17180113
TI  - Sequence of events leading to apoptosis in long term cultured HeLa cells.
AB  - We have maintained HeLa cells in culture in the original medium for increasing
      times to induce growth arrest. Cell viability was evaluated by trypan blue dye
      exclusion assay. We observed that when cells are maintained in culture for
      several days, morphological hallmarks of apoptosis become evident. DNA synthesis
      rate, followed by (3)H-thymidine incorporation slowed down in long term cultured
      cells. This evidence was supported by the analysis of cell cycle progression
      determined by proliferating cell nuclear antigen (PCNA) immunostaining. Apoptotic
      cells have been characterized with respect to the sequential appearance of high
      molecular weight and internucleosomal DNA fragmentation. We have provided
      evidence that in this experimental model the first step in DNA degradation is
      represented by the formation of high molecular weight fragments, whereas
      nucleosomal DNA ladder is visible later on. The activation of the enzyme poly(ADP
      ribose)polymerase, considered a marker of apoptotic death, has been observed. The
      results suggest that long term culture conditions activate the apoptotic
      programme.

PMID- 17180114
TI  - MHC non-restricted, CD95-independent apoptosis of immature thymocytes induced by
      thymic epithelial cells.
AB  - The interaction of thymocytes with thymic epithelial cells in the absence of an
      exogenous antigen was studied in vitro. Thymic, but not splenic epithelial cells
      induced apoptosis of thymocytes. A thymic epithelial cell line (TEC) induced
      apoptosis of thymocytes but not of splenic T-cells. The target population for TEC
      induced death were immature CD4(+)8(+) (double positive), but not mature single
      positive thymocytes. TEC also induced DNA fragmentation in day 18 foetal
      thymocytes, most of which are CD4(+)8(+) cells. Radiation leukemia virus (RadLV)
      transformed thymic lymphoma clones expressing various phenotypes reflected this
      sensitivity, in that a CD4(+)8(+)3(+) clone apoptosed by thymic epithelial cells
      or TEC. Other, single positive or double negative clones were resistant.
      Thymocytes from C3H (H-2(k)), C57BL/6 (H-2(b)) and Balb/C (H-2(d)) mice apoptosed
      equally in response to either C57BL/6 thymic epithelial cells or TEC (H-2(b) x H
      2(d)). Likewise, thymocytes from MRLIpr((-/-)) and B6Ipr((-/-)) mice, which do
      not express CD95 were also apoptosed by TEC.The data suggest that thymic
      epithelial cells induce MHC non-restricted, Fas-independent apoptosis of immature
      thymocytes. This response may reflect a mechanism through which thymocytes
      expressing TcR with no affinity to self MHC/peptide complexes are eliminated.

PMID- 17180115
TI  - Meeting Report: How life may come from death: lessons from reproductive biology.

PMID- 17180116
TI  - Educational Corner: Inhibition of eosinophil apoptosis in chronic allergic
      disease.

PMID- 17180117
TI  - Stable transgene expression in mice generated from retrovirally transduced
      embryonic stem cells.
AB  - Silencing of transduced genes hampers production of transgenic mice using
      retroviral vectors. We show stable expression of the enhanced green fluorescent
      protein (EGFP) gene in chimeric mice generated from retrovirally transduced
      embryonic stem cells. The vector was a murine stem cell virus-typed retroviral
      vector (GCDsap) in which the long terminal repeat and primer-binding site were
      derived from a PCC4 cell-passaged myeloproliferative sarcoma virus and the
      endogenous retrovirus dl587rev, respectively. To increase the viral titer, the
      vector was packaged with vesicular stomatitis virus G protein, which allowed
      concentration of the virus into pellets followed by resuspension in serum-free
      medium. In chimeric mice, EGFP was detected in various tissues including
      hematopoietic cells, neurons, cardiac muscle, and intestine. Furthermore, high
      expression was maintained in the progeny of these mice, suggesting successful
      germline transmission of active proviruses. Although the proportion of EGFP
      expressing cells and the mean intensity of EGFP expression varied among tissues
      and mice, 100% of peripheral blood leukocytes expressed EGFP in mice carrying a
      single provirus copy, as well as in their progeny. Therefore, the gene transfer
      system described here provides a useful tool not only to generate transgenic
      animals but also to manipulate human embryonic stem cells..

PMID- 17180119
TI  - Enhancement of gene transfer to human myeloid cells by adenovirus-fiber
      complexes.
AB  - Adenoviral (Ad) vectors are currently being developed for immunotherapy and
      vaccine delivery, particularly for cancer and antiviral treatment (e.g., human
      immunodeficiency virus vaccine). However, the inefficient transduction of antigen
      presenting cells of myeloid lineage such as dendritic cells (DCs) by conventional
      Ad5-based vectors limits these applications. DCs lack the coxsackie and
      adenovirus receptor but express CD46, a member of the family of complement
      regulatory proteins, as well as sialic acid glycoconjugates, a situation that
      allows infection by Ad type 37 as well as most subgroup B Ads. In this study, we
      generated recombinant Ad fiber knobs (FKs) to probe Ad37 receptor usage on immune
      cells. Remarkably, treatment of human myeloid cells with Ad37 FK (37FK) enhanced,
      rather than inhibited transduction by Ad5 or Ad37 pseudotyped virions. The
      enhanced gene transfer was dose dependent, involved association with alpha(2,6)
      linked sialic acid residues, and was limited to blood cells of myeloid lineage,
      including immature and mature DCs. We also provide evidence that 37FK binds
      directly to Ad5 virus particles, likely acting as a bridge to facilitate greater
      virus-cell interaction.

PMID- 17180118
TI  - Enhanced survival of the LINCL mouse following CLN2 gene transfer using the rh.10
      rhesus macaque-derived adeno-associated virus vector.
AB  - Late infantile neuronal ceroid lipofuscinosis (LINCL) is a lysosomal storage
      disorder caused by mutations in the CLN2 gene and a deficiency of tripeptidyl
      peptidase I (TPP-I). Prior studies with adeno-associated virus (AAV) serotype 2
      or 5 mediated transfer of the CLN2 complementary DNA to the central nervous
      system (CNS) of CLN2(-/-) mice cleared CNS storage granules, but provided no
      improvement in the phenotype or survival of this model of LINCL. In this study,
      AAV serotypes (AAV2, AAV5, AAV8, and AAVrh.10) were compared for the delivery of
      the same CLN2 expression cassette. AAVrh.10, derived from rhesus macaque,
      provided the highest TPP-I level and maximum spread beyond the site of injection.
      The AAVrh.10-based vector functioned equally well in naive rats and in rats
      previously immunized against human serotypes of AAV. When administered to the CNS
      of CLN2(-/-) mice, the AAVrh.10CLN2 vector provided widespread TPP-I activity
      comparable to that in the wild-type mice. Importantly, the AAVrh.10CLN2-treated
      CLN2(-/-) mice had significant reduction in CNS storage granules and demonstrated
      improvement in gait, nest-making abilities, seizures, balance beam function, and
      grip strength, as well as having a survival advantage.

PMID- 17180120
TI  - Modulation of adenoviral transduction in vitro and in vivo by hyaluronan and its
      receptor CD44.
AB  - Adenovirus infection is a significant cause of ocular, respiratory, and
      gastrointestinal illness and can spread rapidly. Morbidity is considerable in
      immune-suppressed individuals and there is significant mortality. There are no
      effective therapies. During preclinical studies of adenoviral-mediated gene
      therapy for ocular disorders, we noticed a significant increase in transduction
      when the target cells were exposed to adenovirus in the presence of ocular
      vitreous. The vitreous is mainly comprised of water, collagen, and the large
      polysaccharide hyaluronan. In this paper, we report data that implicate
      hyaluronan in the adenoviral infectious process and show that interference with
      the interaction between hyaluronan and its cellular receptor CD44 can block
      adenovirus transduction in vitro and in vivo.

PMID- 17180121
TI  - Mutation screening of brain-expressed X-chromosomal miRNA genes in 464 patients
      with nonsyndromic X-linked mental retardation.
AB  - MiRNAs are small noncoding RNAs that control the expression of target genes at
      the post-transcriptional level and have been reported to modulate various
      biological processes. Their function as regulatory factors in gene expression
      renders them attractive candidates for harbouring genetic variants with subtle
      effects on IQ. In an attempt to investigate the potential role of miRNAs in the
      aetiology of X-linked mental retardation, we have examined all 13 known, brain
      expressed X-chromosomal miRNAs in a cohort of 464 patients with non-syndromic X
      linked MR and found four nucleotide changes in three different pre-miRNA
      hairpins. All the observed changes appear to be functionally neutral which, taken
      together with the rarity of detected nucleotide changes in miRNA genes, may
      reflect strong selection and thus underline the functional importance of miRNAs.

PMID- 17180122
TI  - Cystic fibrosis and lactase persistence: a possible correlation.

PMID- 17180123
TI  - Neurobehavioral and immunological consequences of prenatal immune activation in
      rats. Influence of antipsychotics.
AB  - Increasing evidence suggests that pre- or perinatal events that influence the
      immune system contribute to the development of behavioral or neuropsychiatric
      disorders. For instance, exposure of pregnant rats to the bacterial endotoxin
      lipopolysaccharide (LPS) disrupts sensorimotor information processing, as
      assessed by the prepulse inhibition test (PPI), and also the immune function in
      adult offspring, which might be of particular relevance as regards schizophrenia.
      However, the consequences of maternal LPS exposure during pregnancy on synaptic
      functioning in adult offspring and, more importantly, the therapeutic opportunity
      to re-establish PPI and immune function have still to be demonstrated. In this
      work, we analyzed the consequences of prenatal LPS exposure on dopaminergic
      neurotransmission and presynaptic markers in adult brain areas related to PPI
      circuitry. In addition, we tested whether oral treatment with the typical
      antipsychotic drug haloperidol (HAL) could reinstate PPI performances and
      cytokine serum levels in six-month-old male rats with prenatal LPS exposure. Both
      sensory information processing deficits and immune anomalies induced by prenatal
      exposure to LPS were accompanied by changes in dopaminergic neurotransmission and
      synaptophysin expression. It is important to note that PPI disruption and serum
      increases in cytokines induced by prenatal LPS exposure were both reversed by
      HAL. Taken together, these results demonstrate the critical influence of prenatal
      immune events on the functioning of adult nervous and immune systems, in
      association with the putative role of the immune system in the development of
      behavior relevant to schizophrenia.

PMID- 17180125
TI  - Rationale for the administration of acellular pertussis vaccine to parents of
      infants in the neonatal intensive care unit.
AB  - Pertussis infections in the United States are increasing as a consequence of
      waning immunity and increased surveillance. Those most at-risk of mortality
      include infants less than 6 months of age and premature infants. The 2006
      immunization schedule emphasizes an adolescent pertussis booster at 12 years of
      age. However, of concern is the current generation of parents and grandparents
      who will still be un-immunized and therefore, available vectors of pertussis to
      vulnerable neonates. Given the proximity of parents to medical care in the
      Neonatal Intensive Care Unit (NICU), and the potential for severe disease in
      their children, NICU personnel should consider administration of acellular
      pertussis vaccine to parents of hospitalized infants.

PMID- 17180124
TI  - Measurement of brain metabolites in patients with type 2 diabetes and major
      depression using proton magnetic resonance spectroscopy.
AB  - Type 2 diabetes and major depression are disorders that are mutual risk factors
      and may share similar pathophysiological mechanisms. To further understand these
      shared mechanisms, the purpose of our study was to examine the biochemical basis
      of depression in patients with type 2 diabetes using proton MRS. Patients with
      type 2 diabetes and major depression (n=20) were scanned along with patients with
      diabetes alone (n=24) and healthy controls (n=21) on a 1.5 T MRI/MRS scanner.
      Voxels were placed bilaterally in dorsolateral white matter and the subcortical
      nuclei region, both areas important in the circuitry of late-life depression.
      Absolute values of myo-inositol, creatine, N-acetyl aspartate, glutamate,
      glutamine, and choline corrected for CSF were measured using the LC-Model
      algorithm. Glutamine and glutamate concentrations in depressed diabetic patients
      were significantly lower (p<0.001) in the subcortical regions as compared to
      healthy and diabetic control subjects. Myo-inositol concentrations were
      significantly increased (p<0.05) in diabetic control subjects and depressed
      diabetic patients in frontal white matter as compared to healthy controls. These
      findings have broad implications and suggest that alterations in glutamate and
      glutamine levels in subcortical regions along with white matter changes in myo
      inositol provide important neurobiological substrates of mood disorders.

PMID- 17180126
TI  - The labor induction: integrated clinical and sonographic variables that predict
      the outcome.
AB  - OBJECTIVE: To analyze the clinical and sonographic variables that predicts the
      success of labor induction. STUDY DESIGN: We studied the Bishop score, cervical
      length and parity in 196 pregnant women in the prediction of successful vaginal
      delivery within 24 h of induction. Logistic regression and segmentation analysis
      were performed. RESULTS: Cervical length (odds ratio (OR) 1.089, P<0.001), Bishop
      score (OR 0.751, P=0.001) and parity (OR 4.7, P<0.001) predict the success of
      labor induction. In a global analysis of the variables studied, the best
      statistic sequence that predicts the labor induction was found when we introduced
      parity in the first place. The success of labor induction in nulliparous was 50.8
      and 83.3% in multiparous women (P=0.0001). CONCLUSIONS: Cervical length, Bishop
      score and parity, integrated in a flow chart, provide independent prediction of
      vaginal delivery within 24 h of induction.

PMID- 17180127
TI  - Perinatal outcome of quadruplet pregnancies in relation to chorionicity.
AB  - OBJECTIVE: To compare the perinatal outcome of quadruplets in relation to
      chorionicity. PATIENTS AND METHODS: In this retrospective study, the maternal,
      neonatal and chorionicity data were collected from 24 sets of quadruplet
      pregnancies delivered between January 1985 and December 2001. Perinatal and
      neonatal data were evaluated in relation to chorionicity. RESULTS: Sixteen
      pregnancies were quadra-chorionic quadramniotic (QC) and eight had at least one
      monochorionic pair (TC). The median gestational age at delivery was 31 weeks (23
      to 34 weeks) with overall perinatal mortality rate of 177 per 1000 total birth.
      Delivery before 30 weeks (OR 89; 95% CI 9 to 607; P<0.01) and discordant birth
      weight of >25% (OR 7.6; 95% CI 2 to 29; P<0.01) had independent effects on
      perinatal loss rate. The perinatal loss was five fold higher in TC quadruplets
      than those of QC (OR 5.1; 95% CI 1.7 to 15.4; P<0.001). This was attributed to
      higher risk of very low birth weight (69 vs 13%; P<0.01), delivery before 30
      weeks (63 vs 13%; P<0.001) in TC quadruplets compared to QC gestation.
      CONCLUSIONS: The quadruplets with MC pair have 5 times higher perinatal mortality
      than quadra-chorionic quadruplet pregnancies owing to preterm delivery and
      discordant birth weight.

PMID- 17180128
TI  - Treating feeding intolerance with an enteral solution patterned after human
      amniotic fluid: a randomized, controlled, masked trial.
AB  - OBJECTIVE: Feeding intolerance is a common problem in the neonatal intensive care
      unit (NICU) and some cases might be causally related to atrophic changes in the
      small bowel mucosa. We speculated that for such patients, feeding tolerance might
      improve after oral administration of enterocyte growth factors in a sterile,
      isotonic solution patterned after amniotic fluid. STUDY DESIGN: Twenty neonates
      meeting criteria for feeding intolerance were eligible for this trial. They were
      randomized to either Group 1 (test solution) or Group 2 (control). Group 1
      received 2.5 ml of test solution/kg every 3 h by oral-gastric or nasal-gastric
      (OG/NG) tube. This was begun when the patient was NPO because of feeding
      intolerance and continued until 80 ml/k/day of milk feedings were tolerated, or
      for a maximum of 7 days. Group 2 received a sham OG/NG administration every 3 h,
      until 80 ml/k/day of milk feedings were tolerated, or for a maximum of 7 days.
      Only the bedside nurse and the NICU pharmacist were aware which patients received
      the test solution and which received the sham administrations. The volumes of
      milk feedings were increased by order of the attending neonatologist and nurse
      practitioner. The study outcome was enteral calories/kg/day during and for 7 days
      after the cessation of the treatments. RESULTS: Eleven patients were randomized
      to receive the test solution and nine to receive sham administrations. At study
      entry, the two groups were not different in gestational age, postnatal age, signs
      of feeding intolerance or cal/k/day taken enterally during the previous 3 days.
      The study doses were given for an average of just under 6 days (range, 2 to 7
      days). During the week following the administrations, the test solution
      recipients trended toward more enteral calories. Specifically, they had an
      increase averaging 78+/-20.8 cal/k/day more than before the study, whereas the
      sham recipients had an increase averaging 55.9+/-33 cal/k/day more than before
      the study (P=0.05 for a one-sided test and P=0.10 for a two-sided test). The test
      solution recipients also had a trend toward fewer formula changes than did the
      sham recipients (P=0.10). In this small, randomized, controlled, masked trial,
      the administration of a sterile, non-caloric, growth factor containing solution
      patterned after human amniotic fluid was associated with trends that we interpret
      as reflecting better tolerance of milk feedings. On this basis, we suggest that a
      phase III efficacy trial should be accomplished, using the present data for
      sample size calculations.

PMID- 17180129
TI  - Enteral water for hypernatremia and intestinal morbidity in infants less than or
      equal to 1000 g birth weight.
AB  - OBJECTIVE: To evaluate the relationship between enteral water infusion for
      hypernatremia and significant intestinal morbidity in infants <or=1000 grams.
      STUDY DESIGN: This is a retrospective study of 321 infants <or=1000 g birth
      weight. Infants were grouped by the highest serum sodium (mmol/l) during the
      first 14 days of life as follows: <150 (normal control), >or=150 (high sodium
      control), >or=150 and treated with sterile water (study group). Significant
      intestinal morbidity was defined as probable or proven necrotizing enterocolitis
      or spontaneous intestinal perforation. Statistical analysis included Student's t
      test for continuous variables and chi(2) with Yeats correction for frequency
      variables. Multivariate logistic regression analysis was then performed to
      evaluate confounding variables among groups. RESULTS: The incidence of intestinal
      morbidity was significantly higher in the high sodium-water treated group
      compared to each of the other groups (13/33 (38%) for high sodium-water versus
      16/100 (16%) for high sodium control and 18/188 (10%) for normal sodium control,
      P<0.01 chi(2)). Logistic regression analysis indicated that enteral water and
      hydrocortisone were risk factors for significant intestinal morbidity.
      CONCLUSIONS: Enteral sterile water for hypernatremia appears to be associated
      with significant intestinal morbidity in infants <or=1000 g. Hydrocortisone is
      also a risk factor.

PMID- 17180130
TI  - Impact of simple interventions on neonatal mortality in a low-resource teaching
      hospital in India.
AB  - OBJECTIVE: To evaluate impact of simple interventions on neonatal mortality in a
      low-resource teaching hospital in India. STUDY DESIGN: Before-and-after
      intervention trial setting: limited resource teaching hospital; DESIGN: Before
      and after study. INTERVENTIONS: A package of simple interventions was evolved.
      The interventions included: rational admissions and early discharge, entrusting
      mothers in care-giving, enforcing asepsis routines, aggressive enteral feeding,
      abandoning unnecessary interventions, protocol-based management, rational
      antibiotics and training and empowerment of nurses. STATISTICAL METHODS: The
      categorical and continuous variables were compared with chi (2) and two-tailed
      tests, respectively. RESULTS: Neonatal mortality rate declined significantly
      during the intervention period as compared to control period (20.3 versus 29.3
      per 1000 live births; relative risk 0.69, 95% confidence interval (CI) 0.57 to
      0.85). Most significant decline occurred in sepsis-related deaths. The survival
      of neonates with birth weight 1000 to 1499 improved over two folds (56.7% versus
      24.5%, P<0.01). There was a significant decline in antibiotics use (635/878,
      72.3% versus 299/897, 23.2%; P=0.00). The duration of stay in neonatal unit was
      decreased by a mean of 1.5 day (95% CI 0.9 to 2.8 days) after interventions.
      CONCLUSIONS: Simple interventions can result in a significant decline in neonatal
      mortality in hospitals with limited resources. This package is likely to be
      effective in hospitals with a high proportion of the sepsis deaths.

PMID- 17180131
TI  - Global minute: water and health--walking for water and water wars.
AB  - Water is a precious commodity and needs to be conserved. Water plays an important
      role in daily life: in sustenance of life, sanitation and food production.
      Scarcity of water may lead to water wars among water-stressed nations. Therefore,
      there is a need for development of democratic principles among nations to assure
      free access to water to one and all. In view of the fact that lack of access to
      clean water affects health and infant mortality gap. Great importance is given to
      improve water resources in the communities (Millennium Development Goal number
      7). As professionals entrusted with the health of mother and child, we must
      strive to improve access to potable clean water to communities in underdeveloped
      countries.

PMID- 17180132
TI  - Successful term pregnancy following MR-guided focused ultrasound treatment of
      uterine leiomyoma.
AB  - OBJECTIVE: Term vaginal delivery after magnetic resonance-guided focused
      ultrasound therapy (MRgFU) for symptomatic uterine leiomyoma. STUDY DESIGN: A 38
      year-old nulligravida underwent MRgFU treatment per study protocol for a solitary
      9 x 10 x 10 cm uterine myoma and conceived 18 months following the procedure. She
      was counseled on the unknown implications of MRgFU during subsequent pregnancy.
      Myoma size increased significantly during gestation. At 39 weeks, she underwent
      indicated labor induction with vacuum-assisted vaginal delivery of a healthy male
      infant. CONCLUSION: In one pregnancy following MRgFU, there were no associated
      antepartum or intrapartum obstetrical complications.

PMID- 17180134
TI  - Non-sinus bradyarrhythmias in very low birth weight infants.
AB  - Transient bradycardias occur frequently in preterm infants with apnea of
      prematurity. However, occurrence of non-sinus bradyarrhythmias in very low birth
      weight (VLBW) infants has received very little attention. This case series
      documents transient bradyarrhythmias in VLBW infants. Most frequently observed
      arrhythmia was a non-sinus atrial rhythm followed by junctional escape rhythm.
      Ventricular rhythm with wide QRS complexes occurred rarely. The majority of these
      episodes occurred in the absence of oxygen desaturation. Increase in vagal tone
      is presumed to mediate this response.

PMID- 17180133
TI  - Neonatal anemia and hydrops fetalis after maternal mycophenolate mofetil use.
AB  - After admitting a patient to our Neonatal Intensive Care with a severe anemia and
      an ear malformation, we ruled out any other cause than maternal medication use.
      Knowing she used mycophenolate mofetil during pregnancy, we looked for related
      articles. Two articles were found describing ear malformations, but no article
      was ever written about anemia caused by this medication. Consulting the
      international registers of drug effects through the National Institute for Public
      Health and the Environment, we found out that the anemia was never seen or
      reported before.

PMID- 17180135
TI  - Early cystic lung disease in a premature neonate with perinatally acquired
      capnocytophaga.
AB  - We describe a premature infant with early cystic lung lesions and sepsis due to
      prenatally acquired Capnocytophaga infection. Early cystic lesions have not been
      described previously as a characteristic of this infection.

PMID- 17180137
TI  - Myocardial cell therapy at the crossroads.

PMID- 17180136
TI  - Arterial versus total blood volume changes during neural activity-induced
      cerebral blood flow change: implication for BOLD fMRI.
AB  - Quantifying both arterial cerebral blood volume (CBV(a)) changes and total
      cerebral blood volume (CBV(t)) changes during neural activation can provide
      critical information about vascular control mechanisms, and help to identify the
      origins of neurovascular responses in conventional blood oxygenation level
      dependent (BOLD) magnetic resonance imaging (MRI). Cerebral blood flow (CBF),
      CBV(a), and CBV(t) were quantified by MRI at 9.4 T in isoflurane-anesthetized
      rats during 15-s duration forepaw stimulation. Cerebral blood flow and CBV(a)
      were simultaneously determined by modulation of tissue and vessel signals using
      arterial spin labeling, while CBV(t) was measured with a susceptibility-based
      contrast agent. Baseline versus stimulation values in a region centered over the
      somatosensory cortex were: CBF=150+/-18 versus 182+/-20 mL/100 g/min,
      CBV(a)=0.83+/-0.21 versus 1.17+/-0.30 mL/100 g, CBV(t)=3.10+/-0.55 versus 3.41+/
      0.61 mL/100 g, and CBV(a)/CBV(t)=0.27+/-0.05 versus 0.34+/-0.06 (n=7, mean+/
      s.d.). Neural activity-induced absolute changes in CBV(a) and CBV(t) are
      statistically equivalent and independent of the spatial extent of regional
      analysis. Under our conditions, increased CBV(t) during neural activation
      originates mainly from arterial rather than venous blood volume changes, and
      therefore a critical implication is that venous blood volume changes may be
      negligible in BOLD fMRI.

PMID- 17180138
TI  - Cell therapy for cardiac disease: where do we go from here?

PMID- 17180139
TI  - Catheter ablation should not be first-line therapy for atrial fibrillation.

PMID- 17180140
TI  - Are men more at risk of recurrent venous thromboembolism than women?

PMID- 17180142
TI  - Can lipid-lowering medication reduce the prevalence of atrial fibrillation in
      patients with left ventricular dysfunction?

PMID- 17180141
TI  - Can biomarkers improve prediction of future cardiovascular events in patients
      with cardiovascular disease?

PMID- 17180143
TI  - Are there differences in outcome following PCI between patients with STEMI and
      those with non-STEMI?

PMID- 17180144
TI  - Does renal impairment increase mortality risk in patients with heart failure?

PMID- 17180145
TI  - Can cardiac magnetic resonance imaging reclassify uremic cardiomyopathy in
      patients with end-stage renal failure?

PMID- 17180146
TI  - Is clopidogrel associated with poor outcome in patients with non-ST-segment
      elevation ACS after early CABG surgery?

PMID- 17180147
TI  - Interaction of vascular and bone disease in patients with normal renal function
      and patients undergoing dialysis.
AB  - The cardiovascular risk of patients undergoing dialysis is 20-30 times higher
      than that of individuals of the same age, without abnormal renal function, from
      the general population. Observational studies of patients with normal and
      abnormal renal function have shown that there is an association between bone
      disease, vascular calcification and cardiovascular outcome and that worsening of
      these conditions happens in parallel. Basic science studies are elucidating
      several mechanisms that could explain the interaction between bone disease,
      vascular calcification and cardiovascular outcome. For example, the expression of
      osteoprotegerin-a protein that regulates bone resorption by binding receptor
      activator of nuclear factor kappaB (RANK) ligand (RANKL), thus preventing
      interaction with the receptor RANK and the stimulation of osteoclast maturation
      is regulated by several cytokines. Additionally, osteoprotegerin seems involved
      in the genesis of atherosclerosis. Imbalances of bone mineral metabolism, bone
      matrix secretion and vascular smooth-muscle-cell apoptosis seem involved in the
      ossification of the arterial wall in chronic kidney disease, and could explain
      some of the complex interactions between bone and vascular disease in renal
      failure. In this article we present a brief review of some of the basic
      mechanisms involved in vascular calcification and the clinical evidence of an
      association of vascular and bone disease.

PMID- 17180148
TI  - Popular weight-loss diets: from evidence to practice.
AB  - The increasing number of overweight and obese individuals has become one of the
      leading public health concerns in many countries around the world. Concomitant
      with this increase in the prevalence of obesity has been the rise in the number
      of weight-loss diets, many of which alter macronutrient composition, but with the
      majority focused on carbohydrate restriction. Low-carbohydrate diets are
      attractive because they promise rapid weight loss without having to count
      calories and compromise the consumption of many palatable foods. By contrast,
      traditional dietary recommendations for weight loss endorse a fat-restricted and
      calorie-restricted diet high in complex carbohydrates. Evidence indicates that
      low-carbohydrate diets could be better in terms of short-term weight loss
      relative to traditional low-fat diets, but little is known about their long-term
      utility and safety. Diets based on the traditional Mediterranean dietary pattern
      are becoming increasingly popular because of their healthful benefits,
      particularly regarding cardiovascular outcomes. Mediterranean diets encourage
      consumption of a variety of palatable foods, optimizing adherence and
      sustainability. In this Review we discuss the current evidence on the efficacy of
      low-fat, low-carbohydrate and Mediterranean dietary patterns for weight loss,
      their potential mechanisms of action and important clinical considerations.

PMID- 17180149
TI  - Drug insight: aspirin resistance--fact or fashion?
AB  - The term aspirin resistance has been used increasingly in clinical studies. The
      aim of this Review is to analyze the origin of this term, to discuss the
      biochemical, functional and clinical correlates of the phenomenon and to offer a
      conceptual framework to redefine the major determinants of variability between
      individuals in response to aspirin. Awareness needs to be increased of factors
      that might interfere with the desired antiplatelet effect of aspirin,
      particularly in terms of patients' adherence to treatment and avoidable drug
      interactions with some traditional NSAIDs. Gaining such knowledge could result in
      improved care of patients and might avoid the requesting of unnecessary platelet
      function tests of unproven clinical significance.

PMID- 17180150
TI  - Reduction of mitral valve regurgitation caused by acute papillary muscle
      ischemia.
AB  - BACKGROUND: A 67-year-old man was admitted to a coronary care unit for non-ST
      segment elevation myocardial infarction with complicating acute heart failure.
      Severe mitral regurgitation was detected by echocardiography at presentation.
      Repeat echocardiography carried out during another ischemic episode revealed a
      marked reduction in the patient's mitral regurgitation that was related to
      decreased apical traction of the valve leaflets. INVESTIGATIONS: Physical
      examination, electrocardiography, laboratory tests, coronary angiography, chest
      radiography, echocardiography. DIAGNOSIS: Mitral regurgitation associated with
      acute coronary syndrome. MANAGEMENT: Early revascularization by percutaneous
      coronary intervention, supported by pharmacological therapy to decrease left
      ventricular filling pressure.

PMID- 17180151
TI  - Migraine with aura following atrial septostomy for pulmonary arterial
      hypertension.
AB  - BACKGROUND: A 34-year-old woman with known familial pulmonary arterial
      hypertension presented with syncope. Despite medical therapy with an endothelin
      receptor antagonist and a phosphodiesterase inhibitor, the patient had NYHA class
      III symptoms, with exertional dyspnea. Right heart catheterization revealed
      severe pulmonary hypertension (right atrial pressure 15 mmHg, right ventricular
      pressure 80/15 mmHg, pulmonary artery pressure 80/35 mmHg, mean pulmonary artery
      pressure 52 mmHg). The patient underwent balloon atrial septostomy, creating a
      right-to-left shunt. Although she had no history of headaches or migraine
      attacks, the patient developed a migraine headache with aura on the third day
      after the procedure. Migraine attacks recurred for the next 2 days, but symptoms
      were relieved with simple analgesia. INVESTIGATIONS: Physical examination,
      electrocardiography, laboratory testing, 6-min-walk test, right heart
      catheterization, chest radiography, transesophageal echocardiography,
      transthoracic echocardiography. DIAGNOSIS: Migraine with aura following atrial
      septostomy. MANAGEMENT: Bosentan, sildenafil, furosemide, spironolactone and
      warfarin therapy, atrial septostomy, and paracetamol therapy for migraine.

PMID- 17180152
TI  - Preschool children's eating behaviours are related to dietary adequacy and body
      weight.
AB  - OBJECTIVE: The aim of this paper is to analyse the relationships between eating
      behaviours (picky eating, irregular eating and overeating), and dietary adequacy
      in accordance with nutrition recommendations and body weight during the preschool
      years. DESIGN AND SETTING: Our analyses were performed using data from the
      Longitudinal Study of Child Development in Quebec (1998-2002), a population-based
      birth cohort. SUBJECTS: The study followed a representative sample (n=2103) of
      children born in 1998 in the Canadian province of Quebec. METHODS: Eating
      behaviours were derived from self-administered questionnaires when children were
      2.5, 3.5 and 4.5 years. Nutrition data were collected from one 24-hour recall
      interview conducted at home by trained nutritionists at 4.5 years. Children's
      weight and height were measured at 4.5 years. Statistical analyses were carried
      out with SAS (version 8.2). Weighted data adjusted for within-variability were
      used in the analysis, and the significance level was set at 5%. RESULTS: Picky
      eaters consume fewer total fats, less energy and less protein than children never
      reporting picky eating behaviours. Picky eaters were more likely to consume less
      than dietary recommendations for fruit and vegetables, and meat and alternatives.
      Overeaters consumed more total energy and more of each macronutrient than
      children who were never reported as overeaters during the preschool years. These
      children consumed more servings of grain products and meats and alternatives per
      day than children not classified as overeaters. Even when the number of servings
      of grain products consumed was similar for overeaters and children who were never
      overeaters, overeaters had higher body mass index. CONCLUSION: Given that
      children as young as 4.5 years are displaying some form of problematic eating
      behaviour which is shown to be related to dietary adequacy and body weight,
      public health professionals should be targeting parents of young children to
      provide messages about strategies for coping with problematic eating behaviours
      in early childhood.

PMID- 17180153
TI  - A rare mutation in AgRP, +79G>A, affects promoter activity.
AB  - The agouti-related protein is a powerful orexigenic peptide. A rare mutation,
      +79G>A, was identified in its minimal promoter in two white carriers. Comparison
      of the 45-year-old male proband, who was also a carrier of the common Ala67Thr
      polymorphism, with an age- and weight-matching wild-type population showed
      marginal differences for resting metabolic rate (RMR) and body mass index. The
      second carrier however was an obese 57-year-old female with reduced RMR.
      Functional analysis in hypothalamus- and periphery-derived cell lines showed
      reduced promoter activity for the +79A allele in the adrenocortical cells only,
      suggesting that it could affect the peripheral expression levels of AgRP. The
      +79G>A mutation could predispose to body weight gain (as suggested by the
      phenotype of the second carrier), but it could only affect the proband at an
      older age as he may be protected by the Ala67Thr polymorphism that is associated
      with resistance to late-onset fatness.

PMID- 17180154
TI  - Multiple socio-economic circumstances and healthy food habits.
AB  - OBJECTIVE: To examine associations between seven indicators of socio-economic
      circumstances and healthy food habits, while taking into account assumed temporal
      order between these socio-economic indicators. DESIGN AND SETTING: Data were
      derived from cross-sectional postal questionnaires in 2000-2002. Socio-economic
      circumstances were assessed by parental education, childhood economic
      difficulties, own education, occupational class, household income, home ownership
      and current economic difficulties. Healthy food habits were measured by an index
      consisting of consumption of fresh vegetables, fruit or berries, rye bread, fish
      and choosing vegetable fats on bread and oil in cooking. Sequential logistic
      regression models were used, adjusting for age and marital status. PARTICIPANTS:
      Employees of the City of Helsinki, Finland (n=8960, aged 40-60 years). RESULTS:
      Healthy food habits were reported by 28% of women and by 17% of men. Own
      education, occupational class, household income, home ownership and current
      economic difficulties were associated with healthy food habits. These
      associations were attenuated but mainly remained after mutual adjustments for the
      socio-economic indicators. Among women, a pathway was found suggesting that part
      of the effects of education on food habits were mediated through occupational
      class. CONCLUSIONS: Employees in higher and lower socio-economic positions differ
      in their food habits, and those in lower positions and economically disadvantaged
      are less likely to report healthy food habits. Health promotion programmes and
      food policies should encourage healthier food choices among those in lower socio
      economic positions and among those with economic difficulties in particular.

PMID- 17180155
TI  - Prevalence of overweight and obesity in Irish school children, using four
      different definitions.
AB  - OBJECTIVE: To determine the prevalence of overweight and obesity in Irish
      children using four different weight-for-height methods and to examine secular
      trends from previous national data. DESIGN: A cross-sectional survey. Weight and
      height were measured according to standard procedures and used to determine the
      prevalence of overweight and obesity using four weight-for-height methods of
      assessment, actual relative weight, the Centers for Disease Control and
      Prevention body mass index (BMI) for age charts for boys and girls, the BMI
      reference curves for the UK 1990 and the International Obesity Task Force age-
      and sex-specific BMI cutoffs. SETTING: The survey was carried out between 2003
      and 2004 in the Republic of Ireland. SUBJECTS: Random representative sample of
      596 children aged 5-12 years. RESULTS: The prevalence of overweight and obesity
      in Irish children is high, but varies considerably with each method. The
      prevalence of obesity in boys ranged from 4.1 to 11.2 % and in girls from 9.3 to
      16.3%. Between 1990 and 2005, depending on the method used, there was a two-to
      fourfold increase in obesity in children aged 8-12 years. CONCLUSION: It is
      evident given the variation displayed in the prevalence of obesity when using the
      different methods, that there is a discernible need for a single definition to
      identify the obese child in Ireland. The findings show a high prevalence of
      overweight and obesity in Irish school children and the increase in the
      prevalence of obesity over the last 15 years highlights this growing public
      health issue.

PMID- 17180156
TI  - Exercise improves albumin fractional synthetic rate in chronic hemodialysis
      patients.
AB  - OBJECTIVE: To determine whether exercise augments the improvements in fractional
      synthetic rate (FSR) of albumin observed with nutrition alone. DESIGN: Randomized
      crossover study. Each patient randomly participated in two protein metabolism
      kinetic studies using primed-constant infusion of (13C) leucine 2 h before,
      during and 2 h after hemodialysis. Plasma enrichments of (13C) leucine and (13C)
      ketoisocaproate were examined to determine the FSR of albumin. SETTING: General
      Clinical Research Center at Vanderbilt University Medical Center. SUBJECTS: Five
      chronic hemodialysis (CHD) patients. INTERVENTIONS: Intra-dialytic parenteral
      nutrition (IDPN) with or without exercise. RESULTS: Exercise performance during
      hemodialysis significantly improves the FSR of albumin beyond what is observed
      with IDPN alone (26.2+/-3.1% per day versus 17.7+/-1.9% per day, P<0.05).
      CONCLUSION: Exercise improves albumin fractional synthetic rate beyond what is
      observed with IDPN alone in the acute setting in CHD patients.

PMID- 17180157
TI  - Prediction of visceral fat area in Japanese adults: proposal of prediction method
      applicable in a field setting.
AB  - OBJECTIVE: This study aimed to develop a prediction equation for the visceral fat
      area at the umbilical level (VFA(L4-5)) in Japanese adults, using internal fat
      mass (IFM) estimated from a few anthropometric variables. METHODS: Subjects were
      112 adults aged from 25 to 82 years (body mass index (BMI)=24.2+/-3.1 kg/m(2),
      ranged from 15.7 to 31.2 kg/m(2)). Another 60 adults aged from 21 to 71 years
      were recruited for the crossvalidation group (BMI=24.5+/-4.0 kg/m(2), ranged from
      17.1 to 34.6 kg/m(2)). We examined (1) the prediction of IFM based on a small
      number of skinfold thicknesses; (2) the prediction of VFA(L4-5) using IFM and (3)
      the application of bioelectrical impedance analysis (BIA) measurement. VFA(L4-5)
      was measured by computed tomography (reference value). Total fat mass was
      measured by dual-energy X-ray absorptiometry (DXA) and single-frequency BIA with
      8-point tactile electrodes. RESULTS: Three skinfolds at the abdomen, side chest
      and suprailiac were selected to estimate IFM. From IFM estimated using these
      three skinfolds, waist-to-hip ratio (WHR), sex and age, about 75% of the variance
      of VFA(L4-5) could be explained (Eq(VFA)1: R=863, R(2)=0.745, standard error of
      estimate (s.e.e.)=20.483 cm(2)). When substituting IFM based on BIA measurement
      (IFM(BIA)) into Eq(VFA)1, there were no significant mean differences from the
      reference in both equations, and high correlations were found (r=0.860,
      s.e.e.=20.902 cm(2)), although a significant mean difference in total fat mass
      was found between DXA and BIA measurements. The prediction equation using
      IFM(BIA) (Eq(VFA)2) could have prediction accuracy comparable with that of
      Eq(VFA)1 (Eq(VFA)2: R=879, R(2)=0.773, s.e.e.=20.324 cm(2)). Furthermore, when
      applying these equations to the crossvalidation group, there were cross-validity
      in both equations. CONCLUSION: This study proposed a prediction equation for
      VFA(L4-5) from WHR and IFM based on three skinfolds, and the validity of BIA
      measurement in Japanese adults. We can propose the procedure for a field setting.

PMID- 17180158
TI  - Increased body fat percentage and physical inactivity are independent predictors
      of gestational diabetes mellitus in South Asian women.
AB  - OBJECTIVE: This study aims to identify lifestyle predictors of gestational
      diabetes mellitus (GDM) in South Asian women. Pre-gravid body mass index, body
      composition, rate of weight gain during pregnancy, physical activity (PA) and
      dietary intake were studied. DESIGN: Prospective cohort study (n=611) of South
      Asian women at Aga Khan University Hospital antenatal clinic in Karachi,
      Pakistan. Weight, height and body fat % were measured and data on PA, diet and
      socio-economic covariates were collected at baseline. A glucose screen was
      performed at 29.8+/-2.6 weeks. RESULTS: Using logistic regression analysis for
      the full cohort, the risk of GDM increased with older maternal age (odds ratio
      (OR) 1.13, confidence interval (CI) 1.06-1.21), increased body fat % (OR 1.07, CI
      1.03-1.13) and the risk was inversely associated with PA (100 kcal) (OR 0.79
      0.99, CI 0.89). Using a nested case (n=49) control (n=98) design to study dietary
      intake, the risk of GDM decreased with increasing protein (% energy) in the diet
      (OR 0.75, CI 0.60-0.95). CONCLUSIONS: Body fat %, physical inactivity and,
      possibly, diet quality are important modifiable risk factors for GDM. 2006.

PMID- 17180159
TI  - Development of a tomato-based food for special medical purposes as therapy
      adjuvant for patients with HCV infection.
AB  - OBJECTIVE: The present study aimed to develop a food for special medical purposes
      (FSMP) and to assess its efficacy as adjuvant therapy in patients with chronic
      hepatitis C virus (HCV). DESIGN: Open randomized clinical trials with a tomato
      based FSMP used as adjuvant treatment to the pharmacological therapy with
      pegilated interferon and ribavirin. SUBJECTS: Eight healthy volunteers and 39 HCV
      patients. INTERVENTIONS: For the bioavailability study, healthy subjects consumed
      100 g/die FSMP for a week and their serum carotenoid profile at baseline, after
      the week of administration and 7 days later was determined. The same quantity of
      FSMP for 6 months by 20 of the 39 HCV patients was consumed in the clinical
      trial. Serum transaminase, haemoglobin (Hb) and hydroperoxide concentrations
      during the therapy were monitored in all patients. RESULTS: FSMP consumption
      caused a fourfold increase of lycopene serum concentration in healthy subjects. A
      significant increase of carotenoids after 1 month of consumption also in patients
      with HCV was recorded. Transaminase and Hb serum levels, as well as therapeutic
      response, were not influenced by FSMP. The decrease in serum hydroperoxides was
      independent from FSMP consumption in long-term responder patients, whereas
      nonresponder (NR) patients of FSMP group showed higher reductions than NR
      patients of Control group. CONCLUSIONS: The FSMP was effective in improving
      carotenoid status in healthy subjects. In HCV patients, it did not influence the
      therapeutic response, but it prevented carotenoid serum depletion and it was
      effective in improving the oxidative status during antiviral therapy in NR
      patients.

PMID- 17180160
TI  - How to make a mesodiencephalic dopaminergic neuron.
AB  - Dopaminergic neurons located in the ventral mesodiencephalon are essential for
      the control of voluntary movement and the regulation of emotion, and are severely
      affected in neurodegenerative diseases such as Parkinson's disease. Recent
      advances in molecular biology and mouse genetics have helped to unravel the
      mechanisms involved in the development of mesodiencephalic dopaminergic (mdDA)
      neurons, including their specification, migration and differentiation, as well as
      the processes that govern axonal pathfinding and their specific patterns of
      connectivity and maintenance. Here, we follow the developmental path of these
      neurons with the goal of generating a molecular code that could be exploited in
      cell-replacement strategies to treat diseases such as Parkinson's disease.

PMID- 17180161
TI  - HIV and antiretroviral therapy in the brain: neuronal injury and repair.
AB  - Approximately 40 million people worldwide are infected with human
      immunodeficiency virus (HIV). Despite HIV's known propensity to infect the CNS
      and cause neurological disease, HIV neurocognitive disorders remain under
      recognized. Although combination antiretroviral therapy has improved the health
      of millions of those living with HIV, the penetration into the CNS of many such
      therapies is limited, and patients' quality of life continues to be diminished by
      milder, residual neurocognitive impairment. Synaptodendritic neuronal injury is
      emerging as an important mediator of such deficits in HIV. By carefully selecting
      specific antiretrovirals and supplementing them with neuroprotective agents,
      physicians might be able to facilitate innate CNS repair, promoting enhanced
      synaptodendritic plasticity, neural function and clinical neurological status.

PMID- 17180162
TI  - Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron
      networks.
AB  - Gamma frequency oscillations are thought to provide a temporal structure for
      information processing in the brain. They contribute to cognitive functions, such
      as memory formation and sensory processing, and are disturbed in some psychiatric
      disorders. Fast-spiking, parvalbumin-expressing, soma-inhibiting interneurons
      have a key role in the generation of these oscillations. Experimental analysis in
      the hippocampus and the neocortex reveals that synapses among these interneurons
      are highly specialized. Computational analysis further suggests that synaptic
      specialization turns interneuron networks into robust gamma frequency
      oscillators.

PMID- 17180163
TI  - Microglia-mediated neurotoxicity: uncovering the molecular mechanisms.
AB  - Mounting evidence indicates that microglial activation contributes to neuronal
      damage in neurodegenerative diseases. Recent studies show that in response to
      certain environmental toxins and endogenous proteins, microglia can enter an
      overactivated state and release reactive oxygen species (ROS) that cause
      neurotoxicity. Pattern recognition receptors expressed on the microglial surface
      seem to be one of the primary, common pathways by which diverse toxin signals are
      transduced into ROS production. Overactivated microglia can be detected using
      imaging techniques and therefore this knowledge offers an opportunity not only
      for early diagnosis but, importantly, for the development of targeted anti
      inflammatory therapies that might slow or halt the progression of
      neurodegenerative disease.

PMID- 17180164
TI  - Ideas about pain, a historical view.
AB  - The expression 'painful' can be used to describe both an embarrassing moment and
      a cut on the finger. An explanation for this dichotomy can be found in the
      convoluted history of ideas about pain. Whether pain is an independent sensation
      and the product of dedicated neural mechanisms continues to be a topic of debate.
      This overview concentrates on the issue of specificity together with other
      notable information regarding pain that has emerged since 1800.

PMID- 17180165
TI  - A simple adaption to cycling selection: a complex population dynamic explained by
      a single-locus Mendelian model for litter size.

PMID- 17180166
TI  - Conserved gene order belies rapid genome turnover: the dynamic interplay between
      genomic DNA and the outside world.

PMID- 17180167
TI  - An investigation of inbreeding depression and purging in captive pedigreed
      populations.
AB  - We use regression models to investigate the effects of inbreeding in 119 zoo
      populations, encompassing 88 species of mammals, birds, reptiles and amphibians.
      Meta-analyses show that inbreeding depression for neonatal survival was
      significant across the 119 populations although the severity of inbreeding
      depression appears to vary among taxa. However, few predictors of a population's
      response to inbreeding are found reliable. The models are most likely to detect
      inbreeding depression in large populations, that is, in populations in which
      their statistical power is maximised. Purging was found to be significant in 14
      populations and a significant trend of purging was found across populations. The
      change in inbreeding depression due to purging averaged across the 119
      populations is <1%, however, suggesting that the fitness benefits of purging are
      rarely appreciable. The study re-emphasises the necessity to avoid inbreeding in
      captive breeding programmes and shows that purging cannot be relied upon to
      remove deleterious alleles from zoo populations.

PMID- 17180168
TI  - NTP-CERHR monograph on the potential human reproductive and developmental effects
      of methylphenidate.
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for methylphenidate
      to cause adverse effects on reproduction and development in humans.
      Methylphenidate was selected for evaluation because of 1) widespread usage in
      children, 2) availability of developmental studies in children and experimental
      animals, and 3) public concern about the effect of this stimulant on child
      development. Methylphenidate is a central nervous system stimulant approved by
      the U.S. Food and Drug Administration for the treatment of attention deficit
      hyperactivity disorder (ADHD) in persons 6 years of age and older and for
      narcolepsy. The results of this evaluation on methylphenidate are published in an
      NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report
      on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public
      comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP
      reached the following conclusions regarding the possible effects of exposure to
      methylphenidate on human development and reproduction. First, there is negligible
      concern for methylphenidate-induced tics and movement disorders. This conclusion
      is based on studies showing that children treated with therapeutic doses of
      methylphenidate have no evidence of movement disorders or tics due to the
      medication. Second, there is minimal concern for methylphenidate-induced growth
      restriction. This conclusion is based on growth restriction being observed in
      animal studies only at high doses of methylphenidate using a non-therapeutic
      route of exposure. The effect on growth was reversible. Finally, there are
      insufficient data to draw conclusions on 1) an association between
      methylphenidate therapy in pregnant women and pregnancy loss and 2) possible
      reproductive effects of methylphenidate in humans. NTP-CERHR monographs are
      transmitted to federal and state agencies, interested parties, and the public and
      are available in electronic PDF format on the CERHR web site
      http://cerhr.niehs.nih.gov/ and in printed text or CD-ROM from the CERHR.

PMID- 17180170
TI  - Highlights from the 2006 Scientific Sessions of the American Heart Association.

PMID- 17180169
TI  - NTP-CERHR monograph on the potential human reproductive and developmental effects
      of styrene.
AB  - The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human
      Reproduction (CERHR) conducted an evaluation of the potential for styrene to
      cause adverse effects on reproduction and development in humans. Styrene was
      selected for evaluation because of (1) public concern about styrene exposure and
      (2) recently available exposure studies. Styrene (ethenylbenzene; CAS RN: 100-42
      5) is a high production volume chemical (a million pounds or more produced each
      year) and is used in the production of polystyrene resins and as a co-polymer
      with acrylonitrile and 1,3-butadiene. Styrene is found in items such as foam
      cups, dental fillings, matrices for ion exchange filters, construction materials,
      and boats. It is also used in protective coatings, reinforced glass fiber,
      agricultural products, and as a food additive. The Food and Drug Administration
      regulates styrene for use as a synthetic flavoring substance and as a component
      of polymers in contact with dry food, and also regulates the amount of residual
      styrene monomer allowed in polystyrene intended for use in contact with food. The
      public can be exposed to styrene by ingesting food or drink that has been in
      contact with styrene polymers or through inhalation of polluted air and cigarette
      smoke. The results of this evaluation on styrene are published in a NTP-CERHR
      monograph that includes: (1) the NTP Brief, (2) the Expert Panel Report on the
      Reproductive and Developmental Toxicity of Styrene, and (3) public comments
      received on the expert panel report. The NTP reached its conclusion of negligible
      concern for adverse developmental and reproductive effects resulting from styrene
      exposures in humans based on information presented in the NTP-CERHR Expert Panel
      Report on the Reproductive and Developmental Toxicity of Styrene and the public
      comments on that report. This conclusion is based on estimated exposures in both
      the general population and in people whose occupation involves styrene exposure.
      The expert panel estimated styrene exposure in the general U.S. population to be
      less than 0.3 microg/kg body weight/day in nonsmokers and 3.51 and 2.86 microg/kg
      body weight/day in smokers ages 12-19 years and 20-70 years, respectively.
      Average occupational exposures are estimated to range from 1,400-52,000 microg/kg
      body weight/day. Studies in humans show no evidence that occupational exposures
      or exposure of the general population to styrene adversely affect reproduction or
      development. Further, data from experimental animal studies show no adverse
      reproductive or developmental effects at styrene doses far above human exposure
      levels. The NTP will transmit the NTP-CERHR monograph on styrene to federal and
      state agencies, interested parties, and the public and it will be available in
      electronic PDF format on the CERHR web site http://cerhr.niehs.nih.gov and in
      printed text or CD-ROM from the CERHR: M.D. Shelby, Ph.D., Director, CERHR,
      NIEHS, P.O. Box 12233, MD EC-32, Research Triangle Park, NC 27709, 919-541-3455
      [phone], 919-316-4511 [fax], shelby@niehs.nih.gov [email].

PMID- 17180172
TI  - Real-time monitoring for bioaerosols--flow cytometry.
AB  - Bioaerosol detection in real time is an urgent civilian and military requirement.
      In this article, bioaerosol mass spectrometry, an instrument for real-time
      detection of bioaerosols using simultaneous measurement of particle aerodynamic
      size and intrinsic fluorescence, real-time qPCR, and FCM/FL were discussed.
      Although, challenging work remains to determine the interfering substances (e.g.
      particulates) of different environments, distinguish the specific species with
      specific probe, and overcome the high detection limit of FCM (10(4)-10(8) cells
      ml(-1)), literature reports suggested that FCM/FL has a great potential for real
      time monitoring of bioaerosols.

PMID- 17180173
TI  - Toxic metal species and food regulations--making a healthy choice.
AB  - As a safeguard for human health, guidelines and regulations stipulating maximum
      permissible concentrations (MPCs) of metals in foods have been set to limit our
      dietary exposure to toxic metals. It is now well accepted, however, that the
      chemical form of the metal must be considered when assessing the possible human
      health consequences of exposure, and this in turn has led to discussion on the
      incorporation of speciation data in the setting of MPCs for metals in foods. Some
      practical aspects and implications of framing food legislation in terms of metal
      species are presented.

PMID- 17180174
TI  - Super-washing does not leave single walled carbon nanotubes iron-free.
AB  - We demonstrate with transmission electron microscopy and X-ray photoelectron
      spectroscopy that single-walled carbon nanotubes contain significant amounts of
      iron in the form of Fe(3)O(4), which even after acid washing, is not removed.

PMID- 17180175
TI  - Lipid cartography of atherosclerotic plaque by cluster-TOF-SIMS imaging.
AB  - Several frozen vessels bearing atherosclerotic lesion were analysed by cluster
      TOF-SIMS (time-of-flight secondary ion mass spectrometry) to map their lipid
      (fatty acids, cholesterol, vitamin E, phosphatidic acids, phosphatidylinositols
      and triglycerides) content at a micrometric resolution.

PMID- 17180176
TI  - Electrochemical modulation of sickle cell haemoglobin polymerisation.
AB  - Sickle cell haemoglobin (HbS) differs from normal haemoglobin by a single amino
      acid in its beta chain. This amino acid replacement, from glutamic acid to
      valine, causes polymerisation of proteins into defined long insoluble fibres with
      a typical diameter of 21.5 nm. The polymerisation is triggered by the formation
      of deoxyhaemoglobin (deoxyHb) from oxyhaemoglobin (oxyHb) in low oxygen partial
      pressures, which results in a conformational change in the secondary structure of
      the protein. We describe an electrochemical method to modulate the oxygen
      concentration in an optically transparent thin layer cell to produce
      deoxyhaemoglobin whilst monitoring the extent of polymerisation using turbidity
      measurements. The oxygen is depleted in the vicinity of the electrode and
      triggers the polymerisation. The kinetics of polymerisation were investigated
      using a model for fibrillogenesis describing a two-step process of nucleation
      followed by elongation. Rate constants describing the nucleation and growth at
      monomer concentration of 300 mg cm(-3) (4.65 x 10(-3) M) were determined to be
      9.45 (+/-0.08) x 10(-6) s(-1) and 1.22 (+/-0.03) x 10(-3) s(-1) respectively,
      showing that nucleation was far slower than the growth. A similar difference
      between the rate constants for the nucleation (2.99 (+/-0.4) x 10(-8) s(-1)) and
      growth (1.08 (+/-0.2) x 10(-3) s(-1)) was seen at monomer concentration of 50 mg
      cm(-3) (7.75 x 10(-4) M). These results show that nucleation was monomer
      concentration dependent; however growth was largely independent of monomer
      concentration. In this study we present a methodology that may be used as a
      screening method for substances that effect the fibre nucleation and or growth
      that could be valuable to the pharmaceutical industry for treating sickle cell
      disease.

PMID- 17180177
TI  - Analysis of pharmaceutical formulations using atmospheric pressure ion mobility
      spectrometry combined with liquid chromatography and nano-electrospray
      ionisation.
AB  - The hyphenation of liquid chromatography with atmospheric pressure ion mobility
      spectrometry is reported using a custom-made dynamic nano-electrospray ionisation
      (nano-ESI) interface. The analysis of pharmaceutical actives is described,
      including beta blocker (timolol), antidepressant (paroxetine), analgesic
      (paracetamol) and opiate (codeine) preparations. On-line ultraviolet diode array
      (UV) spectroscopic detection was used prior to sample ionisation, to evaluate
      chromatographic and nano-ESI interface performance. Active drug responses were
      characterised by chromatographic retention time and electrophoretic ion mobility
      drift time, and selected ion mobility responses were used to evaluate method
      performance. Limits of detection for active drugs were in the low-nmol to pmol
      range. Quantitative responses were investigated using a series of standard
      solutions of caffeine, showing good linearity (R(2) = 0.9982, n = 6) and
      reproducibility (RSD = 2.3 %, n = 6). The analysis of an over the counter
      pharmaceutical formulation demonstrates the potential of ion mobility
      spectrometry combined with liquid chromatography and nano-electrospray ionisation
      for the rapid determination of active drugs, as a result of the electrophoretic
      separation and selectivity afforded by IMS.

PMID- 17180178
TI  - In vitro continuous amperometric monitoring of 5-hydroxytryptamine release from
      enterochromaffin cells of the guinea pig ileum.
AB  - A diamond microelectrode was used to sensitively, reproducibly and stably record
      overflow of 5-hydroxytryptamine (5-HT, serotonin) from enterochromaffin cells
      (EC) of the intenstinal mucosal layer. 5-HT is an important neurotransmitter and
      paracrine signalling molecule in the gastrointestinal tract. The diamond
      microelectrode was formed by overcoating a sharpened 76 microm diameter Pt wire
      with a thin layer of conducting diamond. After insulation with polypropylene, the
      conically-shaped microelectrode had a diameter of about 10 microm at the tip and
      80 microm at the cylindrical portion. The exposed length was 100-200 microm.
      Continuous amperometry with the microelectrode poised at a detection potential of
      700 mV vs. Ag|AgCl was used to measure 5-HT overflow as an oxidation current. 5
      HT overflow was elicited by both mechanical and electrical stimulation. Some
      minor electrode fouling, a common problem with the oxidative detection of 5-HT,
      was seen for diamond but the response stabilized enabling recording in vitro.
      Both 5-HT and the paracrine hormone, melatonin, were detected in the
      extracellular solution. The 5-HT oxidation current increased in the presence of
      the serotonin transporter (SERT) inhibitor, fluoxetine (1 microM), providing
      evidence that the oxidation current was associated with 5-HT.

PMID- 17180180
TI  - Highly stable electrochemical oxidation of phenolic compounds at carbon ionic
      liquid electrode.
AB  - A carbon ionic liquid electrode (CILE) was used for the investigation of the
      electrochemical oxidation of phenolic compounds in acidic media using cyclic
      voltammetry, chronoamperometry and square wave voltammetry techniques. The
      results indicate that, contrary to many other electrodes, the oxidation of
      phenolic compounds on CILE is highly stable and does not result in electrode
      fouling. Cyclic voltammetry showed that phenolic compounds such as phenol, 2,4
      dichlorophenol and catechol were oxidized at CILE and remained electroactive
      after multiple cycles and at high concentrations of phenol. The cyclic
      voltammetric response of the CILE is very stable with more than 99% of the
      initial activity remaining after 20 s of stirring of a 0.5 mM solution of phenol.

PMID- 17180179
TI  - Depth profiling of calcifications in breast tissue using picosecond Kerr-gated
      Raman spectroscopy.
AB  - Breast calcifications are found in both benign and malignant lesions and their
      composition can indicate the disease state. Calcium oxalate (dihydrate) (COD) is
      associated with benign lesions, however calcium hydroxyapatite (HAP) is found
      mainly in proliferative lesions including carcinoma. The diagnostic practices of
      mammography and histopathology examine the morphology of the specimen. They can
      not reliably distinguish between the two types of calcification, which may
      indicate the presence of a cancerous lesion during mammography. We demonstrate
      for the first time that Kerr-gated Raman spectroscopy is capable of non
      destructive probing of sufficient biochemical information from calcifications
      buried within tissue, and this information can potentially be used as a first
      step in identifying the type of lesion. The method uses a picosecond pulsed laser
      combined with fast temporal gating of Raman scattered light to enable spectra to
      be collected from a specific depth within scattering media by collecting signals
      emerging from the sample at a given time delay following the laser pulse. Spectra
      characteristic of both HAP and COD were obtained at depths of up to 0.96 mm, in
      both chicken breast and fatty tissue; and normal and cancerous human breast by
      utilising different time delays. This presents great potential for the use of
      Raman spectroscopy as an adjunct to mammography in the early diagnosis of breast
      cancer.

PMID- 17180181
TI  - Using blood hemoglobin for blood analysis.
AB  - This paper demonstrates that the spectrophotometric properties of blood
      hemoglobin (Hb) can be used for the direct determination of biochemical compounds
      in blood. Glucose is used as a model, but the methodology can be applied to many
      other compounds (only a previous enzymatic reaction producing H(2)O(2) is
      needed). In order to develop the method, a model relating the Hb absorbance
      variation during the reaction with the glucose concentration has been developed
      to provide theoretical support for the method and to predict its application to
      other compounds. In addition, clear blood samples need to be prepared without pre
      treatment and lateral reactions of H(2)O(2) with other blood constituents need to
      be blocked; this has been achieved with 100 : 1 v/v blood dilution in bi
      distilled water and azide addition. The linear response range of the method can
      be fitted between 2 and 540 mg dL(-1) glucose relative to the original blood
      sample (RSD about 4%, 70 mg dL(-1)). The analyte concentration can be obtained by
      an absolute calibration method or by the standard addition method; both have been
      applied for direct glucose determination in several blood samples and good
      correlations with those obtained by an automatic analyzer have been obtained.

PMID- 17180182
TI  - Score-moment combined linear discrimination analysis (SMC-LDA) as an improved
      discrimination method.
AB  - A new discrimination method called the score-moment combined linear
      discrimination analysis (SMC-LDA) has been developed and its performance has been
      evaluated using three practical spectroscopic datasets. The key concept of SMC
      LDA was to use not only the score from principal component analysis (PCA), but
      also the moment of the spectrum, as inputs for LDA to improve discrimination.
      Along with conventional score, moment is used in spectroscopic fields as an
      effective alternative for spectral feature representation. Three different
      approaches were considered. Initially, the score generated from PCA was projected
      onto a two-dimensional feature space by maximizing Fisher's criterion function
      (conventional PCA-LDA). Next, the same procedure was performed using only moment.
      Finally, both score and moment were utilized simultaneously for LDA. To evaluate
      discrimination performances, three different spectroscopic datasets were
      employed: (1) infrared (IR) spectra of normal and malignant stomach tissue, (2)
      near-infrared (NIR) spectra of diesel and light gas oil (LGO) and (3) Raman
      spectra of Chinese and Korean ginseng. For each case, the best discrimination
      results were achieved when both score and moment were used for LDA (SMC-LDA).
      Since the spectral representation character of moment was different from that of
      score, inclusion of both score and moment for LDA provided more diversified and
      descriptive information.

PMID- 17180183
TI  - Capillary electrophoresis-mass spectrometry of proteins at medium pH using
      bilayer-coated capillaries.
AB  - The feasibility of using noncovalently bilayer-coated capillaries for capillary
      electrophoresis-mass spectrometry (CE-MS) of acidic proteins was investigated
      using background electrolytes (BGEs) of medium pH. The capillary was coated by
      successively rinsing the capillary with solutions of the oppositely charged
      polymers polybrene (PB) and poly(vinyl sulfonic acid) (PVS). Volatile BGEs
      containing ammonium formate and/or N-methyl morpholine were tested at pH 7.5 and
      8.5. Overall, these BGEs provided relatively fast protein separations (analysis
      times of ca. 12 min) and showed high efficiencies (70,000-300,000 plates) when
      the ionic strength was sufficiently high. Migration-time reproducibilities were
      very favorable with RSDs of less than 1.0%. Infusion experiments showed
      satisfactory MS responses for studied proteins dissolved in ammonium formate (pH
      8.5), however, high concentrations of N-methyl morpholine appeared to seriously
      suppress the MS protein signals. Evaluation of the CE-MS system was performed by
      analyzing a mixture of intact proteins yielding efficient separations and good
      quality mass spectra. CE-MS analysis of a reconstituted formulation of the
      biopharmaceutical recombinant human growth hormone (rhGH) which was stored for a
      prolonged time, revealed one degradation product which was provisionally
      identified as desamido rhGH. Based on the MS responses the amount of degradation
      was estimated to be ca. 25%.

PMID- 17180184
TI  - Electron-triggered motions in technomimetic molecules.
AB  - Technomimetic molecules are molecules designed to imitate macroscopic objects at
      the molecular level, also transposing the motions that these objects are able to
      undergo. This article focuses on technomimetic molecules with motions triggered
      by electrons. The first part is devoted to our work in the field of molecular
      switches: after having demonstrated the possibility of controlling an
      intramolecular electron transfer by photoisomerisation, we are now trying to
      control the isomerisation, either by electrochemistry, or by embedding the
      photochromic compound in a self-assembled monolayer and testing the electrical
      conduction with a STM tip. In a second part, we present our strategy on
      controlling the rotation in a molecular rotary motor and the family of ruthenium
      complexes designed to perform such a task. The molecules have a piano-stool
      structure with a "stator" meant to be grafted on an oxide surface, and a "rotor"
      bearing redox-active groups, so that addressing the molecule with nano-electrodes
      would trigger rotation. The electrical control of the charge state of a molecule
      by a STM tip is developed in a final part.

PMID- 17180185
TI  - Homoleptic lanthanide(II)-bis(guanidinate) complexes, [Ln(Giso)(2)] (Giso =
      [(ArN)(2)CN(C(6)H(11))(2)](-), Ar = C(6)H(3)Pr(i)(2)-2,6): planar 4-coordinate
      (Ln = Sm or Eu) vs distorted tetrahedral (Ln = Yb) geometries.
AB  - The first homoleptic lanthanide(II)-guanidinate complexes have been prepared and
      shown to have differing coordination geometries (including unprecedented examples
      of planar 4-coordination) that depend on the size of the lanthanide metal.

PMID- 17180186
TI  - Unexpected reduction pathway of a Co(2+) salt to [HCo(CO)(4)] via [Co(2)(CO)(8)]
      in an ionic liquid.
AB  - In the 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ionic liquid
      ([BMI][NTf(2)]), [Co(NTf(2))(2)] is reduced under 5.5 MPa of H(2)-CO to
      [Co(2)(CO)(8)] prior to [HCo(CO)(4)], provided a pyridine ligand is present in
      the medium.

PMID- 17180187
TI  - Synthesis, electrochemistry and luminescence of [Pt{4'-(R)trpy}(CN)](+) (R = Ph,
      o-CH(3)C(6)H(4), o-ClC(6)H(4) or o-CF(3)C(6)H(4); trpy = 2,2':6',2''
      terpyridine): crystal structure of [Pt{4'-(Ph)trpy}(CN)]BF(4) x CH(3)CN.
AB  - The synthesis and characterization of [Pt{4'-(R)trpy}(CN)]X (R = Ph, X = BF(4) or
      SbF(6); R = o-CH(3)C(6)H(4), X = SbF(6); R = o-ClC(6)H(4), X = SbF(6); or R = o
      CF(3)C(6)H(4), X = SbF(6)) are described where trpy = 2,2':6',2''-terpyridine.
      Single crystals of [Pt{4'-(Ph)trpy}(CN)]BF(4).CH(3)CN were grown by vapour
      diffusion of diethyl ether into an acetonitrile solution of [Pt{4'
      (Ph)trpy}(CN)]BF(4). An X-ray crystal structure determination of the solvated
      complex confirms the near linear coordination of the cyanide ligand to the
      platinum centre. The cation is almost planar as evidenced by a twist of only 1.9
      degrees of the phenyl group out of the plane of the terpyridyl moiety. Cyclic
      voltammograms were recorded in DMF/0.1 M TBAH for the [Pt{4'-(R)trpy}(CN)](+)
      cations. Two quasi-reversible one-electron reduction (cathodic) waves are
      observed with E(1/2) values that show the trend expected for an increasingly
      lower energy of the trpy-based LUMO of the complex i.e., [Pt{4'-(Ph)trpy}(CN)](+)
      approximately [Pt{4'-(o-CH(3)C(6)H(4))trpy}(CN)](+) < [Pt{4'-(o
      ClC(6)H(4))trpy}(CN)](+) < [Pt{4'-(o-CF(3)C(6)H(4))trpy}(CN)](+). All the [Pt(4'
      (R)trpy}(CN)](+) cations are photoluminescent in dichloromethane. Emission by
      [Pt{4'-(Ph)trpy}(CN)](+) is from an excited state with largely (3)MLCT orbital
      parentage, but with some intraligand (3)pi-pi* character mixed-in (tau = 0.1
      micros). In contrast, the other three cations display emission that appears
      exclusively intraligand (3)pi-pi* in origin (tau approximately 0.8 micros).
      Emission spectra have been recorded in a low concentration frozen DME {1 : 5 : 5
      (v/v) DMF-MeOH-EtOH} glass. For the R = o-CH(3)C(6)H(4), o-ClC(6)H(4) and o
      CF(3)C(6)H(4) cations the envelope of vibronic structure and energies of the
      vibrational components are essentially the same as that recorded in
      dichloromethane. However, for the [Pt{4'-(Ph)trpy}(CN)](+) cation, there is a
      blue-shift in the energies of the vibrational components as compared to that
      recorded in dichloromethane, as well as a change in the envelope of vibronic
      structure to a more "domed" pattern; this has been interpreted in terms of a
      higher percentage of intraligand (3)pi-pi* character in the emitting state for
      the glass. Increasing the concentration of the glass invariably leads to
      aggregation of the cations and the consequent development of new low energy
      bands, such that at 0.200 mM broad peaks centred at ca. 650 and 700 nm dominate
      the spectrum; these bands are assigned to excimeric (3)pi-pi* and (3)MMLCT
      emission, respectively.

PMID- 17180188
TI  - Monomeric and polymeric copper and zinc tripyrrins.
AB  - Neutral transition metal complexes of different alpha,omega-dimethyltripyrrins
      TrpyMX with M = Cu(II) and Zn(II) have been prepared with a variety of anionic
      halogeno and pseudohalogeno ligands X, and have been studied with respect to
      coordination modes and structural distortion. Only four- and five-coordinate
      species have been observed throughout the series. All four-coordinate species
      display unstrained, but distorted tetrahedral or strained and distorted square
      planar coordination environments for zinc(II) and copper(II) species,
      respectively, thus following the expectations from simple ligand field arguments.
      Five-coordinate species do not form easily and were observed either in donor
      solvents or in the solid as 1D coordination polymers with distorted trigonal
      bipyramidal coordination and different topologies.

PMID- 17180189
TI  - Bifunctional chelators for copper radiopharmaceuticals: the synthesis of
      [Cu(ATSM)-amino acid] and [Cu(ATSM)-octreotide] conjugates.
AB  - Two new bifunctional chelators that are derivatives of the bis(thiosemicarbazone)
      ATSMH(2) proligand have been prepared, one with two phenyl carboxylate
      substituents on the exocyclic nitrogens (L(1)H(2)) and one with a single phenyl
      carboxylate (L(2)H(2)). The new ligands have been characterised by NMR
      spectroscopy, mass spectrometry and in the case of L(1)H(2) by X-ray
      crystallography. The copper, nickel and zinc complexes of the new ligands have
      been synthesised and characterised. Electrochemical measurements show that the
      copper(II) complexes undergo a reversible reduction attributable to a
      Cu(II)/Cu(I) process. The new proligands have been tethered to the N-alpha-Boc
      protected amino acids lysine and ornithine using solution and solid phase
      methods. The new amino acid conjugates form copper complexes and the complexes
      have been characterised by mass spectrometry and electronic spectroscopy. The
      bifunctional chelator L(2)H(2) has been conjugated to the tumour targeting
      peptide octreotide and the new ATSMH(2)-octreotide conjugate and its copper
      complex have been characterized by mass spectrometry. These new systems have the
      potential to be used for new targeted copper radiopharmaceuticals for imaging and
      therapy.

PMID- 17180190
TI  - Cu(2+) and Pt(2+) complexes of pyrazole and triazole based dinucleating ligands.
AB  - A series of pyrazole and triazole based dinucleating ligands have been
      synthesized and their complexation potential for metal ions, which exhibit square
      planar coordination geometry has been studied. In the case of Cu(2+) the
      complexation equilibria in solution have been determined using pH titrations.
      Species with 1 : 1 stoichiometry [CuLH(n)], 2 : 1 stoichiometry [Cu(2)LH(m)], and
      of dimeric nature [Cu(2)L(2)H(p)], have been detected and their overall stability
      constants have been measured. The reactivity of the dinuclear species [Cu(2)LH(
      1)] towards phosphate ester hydrolysis have shown that the OH-functionality
      incorporated in some of the ligands does not enhance the hydrolysis rate. Several
      ligands were reacted with Pt(2+) to give insoluble dinuclear species
      [Pt(2)LI(3)]. One of them was studied by X-ray diffraction and shows that the two
      Pt(2+) are bridged by the pyrazolide group and by one I(-). The remaining two
      positions are occupied by the amino group in alpha position of the heterocyclic
      ring and a terminal I(-). The nearly planar [Pt(2)LI(3)] units form sheets in the
      crystals, which are about 4 A apart and thus indicate pi stacking interactions.

PMID- 17180191
TI  - Preparation and structural characterization of trimethyltin(IV) tropolonate.
      Investigation of a rare methyl-migrational dismutation in the solution, solid and
      liquid states.
AB  - The synthesis and structural characterisation, by low temperature X-ray
      diffraction and solid-state NMR, of the highly reactive monomeric Me(3)Sn(trop)
      (1) complex has been studied; 1 rearranges into Me(2)Sn(trop)(2) (2) and Me(4)Sn
      by methyl-transfer dismutation. Based on the NMR kinetic data it appears that
      complex demethylates faster in the solid and liquid than in dilute CDCl(3)
      solution, but with a slower rate than in dilute CD(3)OD solution.

PMID- 17180192
TI  - Differences of Eu(III) and Cm(III) chemistry in ionic liquids: investigations by
      TRLFS.
AB  - In this study the coordination structure and chemistry of Eu(III) and Cm(III) in
      the ionic liquid C(4)mimTf(2)N (1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide) was investigated by time-resolved laser
      fluorescence spectroscopy (TRLFS). The dissolution of 1 x 10(-2) M
      Eu(CF(3)SO(3))(3) and 1 x 10(-7) M Cm(ClO(4))(3) in C(4)mimTf(2)N leads to the
      formation of two species for each cation with fluorescence emission lifetimes of
      2.5 +/- 0.2 ms and 1.0 +/- 0.3 ms for the Eu-species and 1.0 +/- 0.3 ms and 300.0
      +/- 50 micros for the Cm-species. The interpretation of the TRLFS data indicates
      a comparable coordination for both the lanthanide and actinide cation in this
      ionic liquid. The quenching influence of Cu(II) on the fluorescence emission of
      Eu(III) and Cm(III) was also measured by TRLFS. While Cu(ii) does not quench the
      Cm(III) fluorescence emission in C(4)mimTf(2)N the Eu(III) fluorescence emission
      lifetime for both Eu-species in C(4)mimTf(2)N decreases with increasing Cu(II)
      concentration. Stern-Volmer constants were calculated (k(SV) = 1.54 x 10(6) M(-1)
      s(-1) and k(SV) = 2.70 x 10(6) M(-1)). By contrast, the interaction of Cu(II)
      with Eu(III) and Cm(III) in water leads to a quenching of both the lanthanide and
      actinide fluorescence. The calculated Stern-Volmer constants are 1.20 x 10(4) M(
      1) s(-1) for Eu(III) and 1.27 x 10(4) M(-1) s(-1) for Cm(III). The investigations
      show, while the chemistry of trivalent lanthanides and actinides is similar in an
      aqueous system it is dramatically different in ionic liquids. This difference in
      chemical behavior may provide the opportunity for a separation of lanthanides and
      actinides with regard to the reprocessing of nuclear fuel.

PMID- 17180193
TI  - Interplay between covalent and aurophilic interactions in a series of
      isostructural 3D Hoffman-like frameworks containing bipyrimidine and
      dicyanoaurate bridges. X-Ray structure and magnetic properties of {(mu
      Au(CN)(2)](2)[(M(NH(3))(2))(2)(mu-bpym)]}[Au(CN)(2)](2) (M = Ni(II), Co(II) and
      Cu(II)).
AB  - The isomorphous coordination polymers {micro-Au(CN)(2)](2)[(M(NH(3))(2))(2)(mu
      bpym)]}[Au(CN)(2)](2) (M = Co(II) (1), Ni(II) (2), Cu(II) (3)) have been prepared
      from the reaction of 2 equiv. M(NO(3))(2) x nH(2)O (M = Cu(II), n = 3; M = Ni(II)
      and Co(II), n = 6) with 1 equiv. of bipyrimidine (bpym) in aqueous ammonia and
      then with an aqueous solution containing 1 equiv. of K[Au(CN)(2)]. The structures
      of these complexes are made of bpym bridged centrosymmetric dinuclear
      [M(NH(3))(2)(mu-bpym)M(NH(3))(2)] units connected by [Au(CN)(2)](-) anions to
      four other dinuclear units giving rise to a cationic 2D (4,4) rectangular grid
      network, its charge being balanced by two non-coordinated [Au(CN)(2)](-). The
      layers are stacked in such a way that the ammonia coordinated molecules are
      interdigitated and aligned above and below one sheet with cavities in
      neighbouring sheets, giving rise to an ABAB[dot dot dot] repeat pattern of
      layers. Gold atoms of bridging and non-bridging dicyanoaurate anions are involved
      in short aurophilic interactions (Au1-Au2 distances in the range 3.12-3.14
      Angstrom), leading to a chain of gold atoms running along the a direction.
      Neighbouring gold chains are further connected by weaker aurophilic interactions
      (Au1-Au1 distances in the range 3.43-3.49 Angstrom), affording a honeycomb-like
      2D network of gold atoms. The (4,4) rectangular sheets and (6,3) honeycomb sheets
      share the Au2 atoms, leading to a unique 3D network. Magnetic measurements
      clearly show the existence of antiferromagnetic exchange coupling between the
      metal ions with susceptibility maxima at 17 K (1), 22 K (2), and 17 K (3). The
      data of 1 were analyzed through a full Hamiltonian involving spin-orbit coupling,
      axial distortion, Zeeman interactions and magnetic exchange coupling between
      Co(II), and the best fit gives J = -9.23 cm(-1), kappa = 0.99, lambda = -142 cm(
      1), Delta = -562 cm(-1). For 2 and 3, magnetic data were fitted to the
      theoretical equations derived from the isotropic Hamiltonian: H = -JS(1)S(2). The
      best fit parameters were g = 2.050(1), J = -17.51(1) and P = 0.01(2) for 2 and g
      = 2.068(5), J = -20.07(8) and P = 0.015(4) for 3, respectively (P takes into
      account the amount of paramagnetic impurity). In order to explain the weak
      magnetic interaction between copper(II) ions mediated by the bipyrimidine
      bridging ligand in 3, we have carried out electronic structure calculations based
      on the density functional theory (DFT).

PMID- 17180194
TI  - Alkali metal complexes of sterically demanding amino-functionalized secondary
      phosphanide ligands.
AB  - The reaction between {(Me(3)Si)(2)CH}PCl(2) (4) and one equivalent of either
      [C(6)H(4)-2-NMe(2)]Li or [2-C(5)H(4)N]ZnCl, followed by in situ reduction with
      LiAlH(4) gives the secondary phosphanes {(Me(3)Si)(2)CH}(C(6)H(4)-2-NMe(2))PH (5)
      and {(Me(3)Si)(2)CH}(2-C(5)H(4)N)PH (6) in good yields as colourless oils.
      Metalation of 5 with Bu(n)Li in THF gives the lithium phosphanide
      [[{(Me(3)Si)(2)CH}(C(6)H(4)-2-NMe(2))P]Li(THF)(2)] (7), which undergoes
      metathesis with either NaOBu(t) or KOBu(t) to give the heavier alkali metal
      derivatives [[{(Me(3)Si)(2)CH}(C(6)H(4)-2-NMe(2))P]Na(tmeda)] (8) and
      [[{(Me(3)Si)(2)CH}(C(6)H(4)-2-NMe(2))P]K(pmdeta)] (9) after recrystallization in
      the presence of the corresponding amine co-ligand [tmeda = N,N,N',N'
      tetramethylethylenediamine, pmdeta = N,N,N',N'',N''
      pentamethyldiethylenetriamine]. The pyridyl-functionalized phosphane 6 undergoes
      deprotonation on treatment with Bu(n)Li to give a red oil corresponding to the
      lithium compound [{(Me(3)Si)(2)CH}(2-C(5)H(4)N)P]Li (10) which could not be
      crystallized. Treatment of this oil with NaOBu(t) gives the sodium derivative
      [{[{(Me(3)Si)(2)CH}(2-C(5)H(4)N)P]Na}(2) x (Et(2)O)](2) (11), whilst treatment of
      with KOBu(t), followed by recrystallization in the presence of pmdeta gives the
      complex [[{(Me(3)Si)(2)CH}(2-C(5)H(4)N)P]K(pmdeta)](2) (12). Compounds 5-12 have
      been characterised by (1)H, (13)C{(1)H} and (31)P{(1)H} NMR spectroscopy and
      elemental analyses; compounds 7-9, and 12 have additionally been characterised by
      X-ray crystallography. Compounds 7-9 crystallize as discrete monomers, whereas 11
      crystallizes as an unusual dimer of dimers and 12 crystallizes as a dimer with
      bridging pyridyl-phosphanide ligands.

PMID- 17180195
TI  - The molecular structure of N-fluorobis(trifluoromethanesulfonyl)imide,
      NF(SO(2)CF(3))(2), as studied in the gas phase by electron diffraction restrained
      by ab initio calculations.
AB  - The structure of N-fluorobis(trifluoromethylsulfonyl)imide, prepared by a
      relatively safe and easy method, has been determined by gas-phase electron
      diffraction (GED), employing the SARACEN method, with flexible restraints based
      on the MP2/6-311G* structure, and by X-ray crystallography at 150 K. The strongly
      electron-withdrawing CF(3) and SO(2)CF(3) groups make the C-S and N-S distances
      long, averaging 187.7(3) and 171.7(3) pm, respectively, in the gas phase. The gas
      consists of two conformers, one (75%) with a CF(3) group on each side of the SNS
      plane, one anti-periplanar and one syn-periplanar to the further N-S bond (ap,
      sp), and the other with both CF(3) groups on the same side, i.e. denoted ap, ap.
      These conformers have very different SNS angles, 126.9(9) degrees and 117.1(17)
      degrees respectively. In the crystal all molecules have the ap, sp conformation,
      with parameters similar to those found for this conformer in the gas phase.

PMID- 17180196
TI  - Novel palladium complexes employing mixed phosphine phosphonates and phosphine
      phosphinates as anionic chelating [P,O] ligands.
AB  - A route to various substituted phosphine phosphonic acid compounds of the general
      form Ar(2)PC(6)H(4)PO(OH)(2) (Ar = Ph, o-MeC(6)H(4), o-MeOC(6)H(4)) has been
      investigated. These compounds were employed as bidentate anionic [P,O] ligands in
      neutral palladium complexes. The [P,O] chelating coordination was determined by X
      ray crystallography of a representative palladium complex. Furthermore, the
      bifunctional ligand Ph(2)PC(6)H(4)PO(OH)Ph represents the first example of a
      chelating anionic [P,O] ligand resulting from the combination of a phosphine and
      a phosphinate moiety.

PMID- 17180200
TI  - Nanowire electrochemical sensors: can we live without labels?

PMID- 17180201
TI  - Solvent resistant microfluidic DNA synthesizer.
AB  - We fabricated a microfluidic DNA synthesizer out of perfluoropolyether (PFPE), an
      elastomer with excellent chemical compatibility which makes it possible to
      perform organic chemical reactions, and synthesized 20-mer oligonucleotides on
      chip.

PMID- 17180202
TI  - An integrated fluorescence detection system for lab-on-a-chip applications.
AB  - We present a low-cost miniaturized fluorescence detection system for lab-on-a
      chip applications with a sensitivity in the low nanomolar range; a built-in lock
      in amplifier enables measurements under ambient light.

PMID- 17180203
TI  - Microtechnology: meet neurobiology.
AB  - The field of neuroscience has always been attractive to engineers. Neurons and
      their connections, like tiny circuit elements, process and transmit information
      in a dramatic way that is intimately curious to researchers in the computer
      science and engineering fields. Of particular interest has been the recent push
      in applying microtechnology to the field of neuroscience. This review is meant to
      provide an overview of some of the subtle nuances of the nervous system and
      outline recent advances in lab on a chip applications in neurobiology. It also
      aims to highlight some of the challenges the field faces in the hopes of
      encouraging new engineering researchers to collaborate with neurobiologists to
      help advance our basic understanding of the nervous system and create novel
      applications based on neuroengineering principles.

PMID- 17180204
TI  - Lab-on-a-chip devices for global health: past studies and future opportunities.
AB  - A rapidly emerging field in lab-on-a-chip (LOC) research is the development of
      devices to improve the health of people in developing countries. In this review,
      we identify diseases that are most in need of new health technologies, discuss
      special design criteria for LOC devices to be deployed in a variety of resource
      poor settings, and review past research into LOC devices for global health. We
      focus mainly on diagnostics, the nearest-term application in this field.

PMID- 17180205
TI  - Integrated thin-film polymer/fullerene photodetectors for on-chip microfluidic
      chemiluminescence detection.
AB  - We report the use of solution-processed thin-film organic photodiodes for
      microscale chemiluminescence. The active layer of the photodiodes comprised a 1 :
      1 blend by weight of the conjugated polymer poly(3-hexylthiophene) [P3HT] and
      [6,6]-phenyl-C(61)-butyric acid-methylester [PCBM]--a soluble derivative of
      C(60). The devices had an active area of 1 mm x 1 mm, and a broad-band response
      from 350 to 700 nm, with an external quantum efficiency of more than 50% between
      450 and 550 nm. The photodiodes have a simple layered structure that permits
      facile integration with planar chip-based systems. To evaluate the suitability of
      the organic devices as integrated detectors for microscale chemiluminescence, a
      peroxyoxalate based chemiluminescence reaction (PO-CL) was monitored within a
      poly(dimethyl-siloxane) (PDMS) microfluidic device. Quantitation of hydrogen
      peroxide indicated excellent linearity and yielded a detection limit of 10
      microM, comparable with previously reported results using micromachined silicon
      microfluidic chips with integrated silicon photodiodes. The combination of
      organic photodiodes with PDMS microfluidic chips offers a means of creating
      compact, sensitive and potentially low-cost microscale CL devices with wide
      ranging applications in chemical and biological analysis and clinical
      diagnostics.

PMID- 17180206
TI  - Characterization of fibrinogen adsorption onto glass microcapillary surfaces by
      ELISA.
AB  - Adsorption of biomolecules onto microchannel surfaces remains a critical issue in
      microfluidic devices. This paper investigates the adsorption of fibrinogen on
      glass microcapillaries using an immunoassay method (ELISA) and X-ray
      photoelectron spectroscopy (XPS). Various adsorption conditions such as protein
      concentrations and incubation times, buffer pH, buffer ionic strengths and
      effects of flow are presented. ELISA is successfully demonstrated as a facile and
      robust technique to examine these phenomena. The highest adsorption level occurs
      near the isoelectric point of fibrinogen (pH 5.0) and low buffer ionic strengths
      (0-8 mM). Microchannel surface saturation was achieved at a fibrinogen solution
      concentration of approximately 50 microg ml(-1). Fibrinogen adsorption under flow
      was always higher than that seen in static systems. The importance of diffusion
      phenomena in microchannels on protein adsorption was demonstrated. ELISA
      experiments using fused silica and PEEK have also confirmed significant
      adsorption on these mass spectrometer transfer line materials.

PMID- 17180207
TI  - A microfluidic system in combination with optical tweezers for analyzing rapid
      and reversible cytological alterations in single cells upon environmental
      changes.
AB  - We report on the development of an experimental platform where epi-fluorescence
      microscopy and optical tweezers are combined with a microfluidic system to enable
      the analysis of rapid cytological responses in single cells. The microfluidic
      system allows two different media to be merged in a Y-shaped channel. Microscale
      channel dimensions ensure purely laminar flow and, as a result, an environmental
      gradient can be created between the two media. Optical tweezers are used to move
      a single trapped cell repeatedly between the different environments. The cell is
      monitored continuously by fluorescence microscopy during the experiment. In a
      first experiment on yeast (Saccharomyces cerevisiae) we observed changes in cell
      volume as the cell was moved between environments with different osmolarity. This
      demonstrated that the platform allowed analysis of cytological alterations on a
      time scale shorter than 0.2 s. In a second experiment we observed the spatial
      migration of the Yap1p transcription factor fused to GFP as a cell was moved from
      an environment of low to high oxidative capacity. The system is universal
      allowing the response to numerous environmental changes to be studied on the sub
      second time scale in a variety of model cells. We intend to use the platform to
      study how the age of cells, their progression through the cell cycle, or their
      genetic landscape, alter their capacity (kinetics and amplitude) to respond to
      environmental changes.

PMID- 17180209
TI  - Enhancement of an electroporation system for gene delivery using electrophoresis
      with a planar electrode.
AB  - In this paper a new electroporation (EP) system is developed, which includes an
      EP microchip and a logic circuit, which combined with electrophoresis (ES), can
      provide site-specific enhancement of gene concentration. In this ES-EP microchip,
      an arc planar electrode provides the ES function for DNA attraction, and
      interdigitated array electrodes provide appropriate electric fields for the EP on
      the chip surface. In addition, the adherent cells can be manipulated in situ
      without detachment of the ES-EP microchip, which performs the "Lab on a chip".
      Experimental results have shown that the efficiency of gene transfection with an
      attracting-electric field (35.89%) becomes much higher than that without an
      attracting-electric field (16.62%). Cell numbers as low as 10(4) cells, and DNA
      as little as 4 microg are sufficient for evaluating the phenotypic effects
      following the over-expression of the introduced genes on the ES-EP microchip. The
      proposed system has the advantages of portability, cost-effectiveness, a high
      transfection rate and ease of operation.

PMID- 17180210
TI  - Quantitative on-chip determination of taurine in energy and sports drinks.
AB  - A new method for the quantitative determination of taurine in beverages by
      microchip electrophoresis was developed. A rapid and simple sample preparation
      procedure, only including two dilution steps and the addition of the fluorogenic
      labeling reagent NBD-Cl (4-chloro-7-nitrobenzofurazan), is applied. Using a home
      built wavelength-resolved fluorescence detector, the separation and determination
      of the taurine derivative could be achieved in only 12 s, while the additional
      spectral information was utilized to ensure peak purity. Spanning from 0.1 to 50
      mmol L(-1), the linear dynamic range of the applied method was adapted to the
      apparent contents in common taurine containing beverages. The smallest detectable
      amount of the taurine derivative actually injected into the separation channel
      was as low as 60 amol. The method was successfully validated by an independent
      liquid chromatographic method.

PMID- 17180208
TI  - A high-throughput microfluidic real-time gene expression living cell array.
AB  - The dynamics of gene expression are fundamental to the coordination of cellular
      responses. Measurement of temporal gene expression patterns is currently limited
      to destructive low-throughput techniques such as northern blotting, reverse
      transcription polymerase chain reaction (RT-PCR), and DNA microarrays. We report
      a scalable experimental platform that combines microfluidic addressability with
      quantitative live cell imaging of fluorescent protein transcriptional reporters
      to achieve real-time characterization of gene expression programs in living
      cells. Integrated microvalve arrays control row-seeding and column-stimulation of
      256 nanoliter-scale bioreactors to create a high density matrix of stimulus
      response experiments. We demonstrate the approach in the context of hepatic
      inflammation by acquiring approximately 5000 single-time-point measurements in
      each automated and unattended experiment. Experiments can be assembled in hours
      and perform the equivalent of months of conventional experiments. By enabling
      efficient investigation of dynamic gene expression programs, this technology has
      the potential to make significant impacts in basic science, drug development, and
      clinical medicine.

PMID- 17180211
TI  - Electrophoretic partitioning of proteins in two-phase microflows.
AB  - This work reports on protein transport phenomena discovered in partitioning
      experiments with a novel setup for continuous-flow two-phase electrophoresis
      consisting of a microchannel in which a phase boundary is formed in flow
      direction. Proteins can be partitioned exploiting their affinity to different
      aqueous phases in two-phase systems. This separation process may be enhanced or
      extended by applying an electric field perpendicular to the phase boundary. In
      this context, microsystems offer new possibilities, as interfacial forces usually
      dominate over volume forces, thus allowing a superior control of the formation
      and arrangement of liquid/liquid phase boundaries. The two immiscible phases
      which are injected separately into the microchannel are taken from a polyethylene
      glycol (PEG)-dextran system. The side walls of the channel are partially made of
      gel material which serves as an ion conductor and decouples the channel from the
      electrodes, thus preventing bubble generation inside the separation channel. The
      experiments show that the electrophoretic transport of proteins between the
      laminated liquid phases is characterized by a strong asymmetry. When bovine serum
      albumin (BSA) is introduced into the PEG-rich phase, it can easily be transferred
      into the dextran-rich phase via an applied electric field of low strength or just
      by diffusion. In the reverse case, up to a certain field strength the transfer to
      the opposing phase is strongly inhibited. Only if the field strength is further
      increased will the BSA molecules leave the dextran-rich phase almost completely.

PMID- 17180212
TI  - Mechano-transduction of DNA hybridization and dopamine oxidation through
      electrodeposited chitosan network.
AB  - While microcantilevers offer exciting opportunities for mechano-detection, they
      often suffer from limitations in either sensitivity or selectivity. To address
      these limitations, we electrodeposited a chitosan film onto a cantilever surface
      and mechano-transduced detection events through the chitosan network. Our first
      demonstration was the detection of nucleic acid hybridization. In this instance,
      we electrodeposited the chitosan film onto the cantilever, biofunctionalized the
      film with oligonucleotide probe, and detected target DNA hybridization by
      cantilever bending in solution (static mode) or resonant frequency shifts in air
      (dynamic mode). In both detection modes, we observed a two-order of magnitude
      increase in sensitivity compared to values reported in literature for DNA
      immobilized on self-assembled monolayers. In our second demonstration, we coupled
      electrochemical and mechanical modes to selectively detect the neurotransmitter
      dopamine. A chitosan-coated cantilever was biased to electrochemically oxidize
      dopamine solution. Dopamine's oxidation products react with the chitosan film and
      create a tensile stress of approximately 1.7 MPa, causing substantial cantilever
      bending. A control experiment was performed with ascorbic acid solution. It was
      shown that the electrochemical oxidation of ascorbic acid does not lead to
      reactions with chitosan and does not change cantilever bending. These results
      suggest that chitosan can confer increased sensitivity and selectivity to
      microcantilever sensors.

PMID- 17180213
TI  - On-chip pumping for pressure mobilization of the focused zones following
      microchip isoelectric focusing.
AB  - Isoelectric focusing (IEF), traditionally accomplished in slab or tube gels, has
      also been performed extensively in capillary and, more recently, in microchip
      formats. IEF separations performed in microchips typically use electroosmotic
      flow (EOF) or chemical treatment to mobilize the focused zones past the detection
      point. This report describes the development and optimization of a microchip IEF
      method in a hybrid PDMS-glass device capable of controlling the mobilization of
      the focused zones past the detector using on-chip diaphragm pumping. The
      microchip design consisted of a glass fluid layer (separation channels), a PDMS
      layer and a glass valve layer (pressure connections and valve seats). Pressure
      mobilization was achieved on-chip using a diaphragm pump consisting of a series
      of reversible elastomeric valves, where a central diaphragm valve determined the
      volume of solution displaced while the gate valves on either side imparted
      directionality. The pumping rate could be adjusted to control the mobilization
      flow rate by varying the actuation times and pressure applied to the PDMS to
      actuate the valves. In order to compare the separation obtained using the chip
      with that obtained in a capillary, a serpentine channel design was used to match
      the separation length of the capillary, thereby evaluating the effect of
      diaphragm pumping itself on the overall separation quality. The optimized mIEF
      method was applied to the separation of labeled amino acids.

PMID- 17180214
TI  - Capillary pumps for autonomous capillary systems.
AB  - Autonomous capillary systems (CSs), where liquids are displaced by means of
      capillarity, are efficient, fast and convenient platforms for many bioanalytical
      applications. The proper functioning of these microfluidic devices requires
      displacing accurate volumes of liquids with precise flow rates. In this work, we
      show how to design capillary pumps for controlling the flow properties of CSs.
      The capillary pumps comprise microstructures of various shapes with dimensions
      from 15-250 microm, which are positioned in the capillary pumps to encode a
      desired capillary pressure. The capillary pumps are designed to have a small flow
      resistance and are preceded by a constricted microchannel, which acts as a flow
      resistance. Therefore, both the capillary pump and the flow resistance define the
      flow rate in the CS, and flow rates from 0.2-3.7 nL s(-1) were achieved. The
      placement and the shape of the microstructures in the capillary pumps are used to
      tailor the filling front of liquids in the capillary pumps to obtain a reliable
      filling behaviour and to minimize the risk of entrapping air. The filling front
      can, for example, be oriented vertically or tilted to the main axis of the
      capillary pump. We also show how capillary pumps having different hydrodynamic
      properties can be connected to program a sequence of slow and fast flow rates in
      a CS.

PMID- 17180215
TI  - Containerless reaction monitoring in ionic liquids by means of Raman
      microspectroscopy.
AB  - Reaction monitoring by Raman microspectroscopy in levitated room temperature
      ionic liquid (RTIL) droplets is reported. Due to their non-volatility, RTIL
      droplets are well-suited to act as wall-less microreactors. The droplets were
      produced by a piezoelectric flow-through microdispenser connected to an automated
      flow injection system and were levitated by an acoustic trap. Taking advantage of
      the flow system versatility, the sequence of reagents was easily changed to study
      a model organic reaction: the Knoevenagel condensation. The reaction was followed
      by Raman microspectrometry and the obtained spectra were analysed using
      multivariate curve resolution to retrieve the concentration profiles and pure
      spectra of reactants, intermediates and products involved in the reaction. In
      addition, information about solvation interactions was obtained by monitoring the
      desolvation process taking place when a volatile co-solvent evaporated from the
      droplet.

PMID- 17180216
TI  - Novel microfibrous composite bed reactor: high efficiency H2 production from NH3
      with potential for portable fuel cell power supplies.
AB  - A novel microfibrous composite bed reactor was developed and was demonstrated for
      high efficiency hydrogen production by the decomposition of ammonia at moderate
      temperatures in portable fuel cell power system applications. By using a high
      speed and low-cost papermaking technology combined with a subsequent sintering
      process, sinter-locked three-dimensional microfibrous networks consisting of
      approximately 3 vol% 8 microm (dia.) nickel microfibers were utilized to entrap
      approximately 35 vol% 100-200 microm dia. porous Al(2)O(3) support particulates.
      A CeO(2) promoter and active Ni component were then dispersed onto the pore
      surface of the entrapped Al(2)O(3) support particulates by a stepwise incipient
      wetness impregnation method. The microfibrous structure took advantage of a large
      void volume, entirely open structure, high heat/mass transfer, high permeability,
      good thermal stability, and unique form factors. Addition of ceria significantly
      promoted the low-temperature activity of Ni/Al(2)O(3) catalyst particulates
      incorporated into the micorfibrous structure. The use of fine particles of
      catalyst significantly attenuated the intraparticle mass transport limitations.
      As a result, the present novel microfibrous composite bed reactor provided
      excellent activity and structure stability in ammonia decomposition, as well as
      low pressure drop and high efficiency reactor design. At a 90% conversion of a
      145 sccm ammonia feed rate, the microfibrous entrapped Ni/CeO(2)-Al(2)O(3)
      catalyst composite bed could provide a 4-fold reduction of catalytic bed volume
      and a 5-fold reduction of catalytic bed weight (or 9-fold reduction of catalyst
      dosage), while leading to a reduction of reaction temperature of 100 degrees C,
      compared to a packed bed with 2 mm dia. Ni/CeO(2)-Al(2)O(3) catalyst pellets.
      This composite bed was capable of producing roughly 22 W of hydrogen power, with
      an ammonia conversion of 99% at 600 degrees C in a bed volume of 0.5 cm(3)
      throughout a 100 h continuous test. These initial and promising results
      established that the microfibrous nickel-based catalyst composites were effective
      for high efficiency production of hydrogen by ammonia decomposition, while
      achieving a significant reduction of overall catalytic bed weight and volume. We
      anticipate our assay to be a new point for small-scale hydrogen production, where
      the microfibrous catalytic reactors considered in isolation can satisfy several
      of the most fundamental criteria needed for useful operation.

PMID- 17180217
TI  - Scaling out of electrolyte free electrosynthesis in a micro-gap flow cell.
AB  - The electro-reductive coupling of activated olefins and benzyl bromide
      derivatives has been selected to compare the performance of single and multiple
      channel (scaled-out) micro-gap electrochemical flow reactors. Two working
      electrode configurations were evaluated; in the first a single set of electrodes
      was used in conjunction with a multiple flow manifold to give two and four
      separate flow channels; in the second independent electrodes were used within the
      same flow manifold. Problems with shunt currents and Joule heating in the first
      configuration meant that only the second configuration was reliable, giving
      results comparable to those obtained for the single flow cell. Excellent yields
      of the coupling products such as 2-benzyl-succinic acid dimethyl ester and
      derivatives were obtained. This demonstrates micro reactor scale-out for
      unsupported electrosyntheses.

PMID- 17180219
TI  - Imprinting and locking chiral memory for stereoselective catalysis.
AB  - A salen ligand based Co(III) complex +/- with imprintable chiral memory was
      locked-in and used for stereoselective catalysis.

PMID- 17180218
TI  - Molecular and supramolecular C60-oligophenylenevinylene conjugates.
AB  - Fullerene derivatives are attractive building blocks for the preparation of
      molecular and supramolecular photoactive devices. As a part of this research,
      combination of C60 with oligophenylenevinylene (OPV) subunits has generated
      significant research efforts. These results are summarized in the present account
      to illustrate the current state-of-the-art of fullerene chemistry for the
      development of new photoactive materials.

PMID- 17180220
TI  - Large continuous, transparent and oriented self-supporting films of layered
      double hydroxides with tunable chemical composition.
AB  - Highly ordered transparent self-supporting films of layered double hydroxides
      (LDHs) with a size of the order of cm2 have been obtained by a simple method; the
      chemical composition of both the layers and interlayers can be readily tuned, as
      demonstrated by the preparation of [ZnAl-NO3] LDH, [NiAl-NO3] LDH and [Tb(EDTA)]-
      intercalated-ZnAl LDH films.

PMID- 17180221
TI  - Formazans as beta-diketiminate analogues. Structural characterization of
      boratatetrazines and their reduction to borataverdazyl radical anions.
AB  - Formazans react with boron triacetate to produce boratatetrazines, which can be
      reduced to yield borataverdazyl radical anions--the first boron containing
      verdazyl radicals.

PMID- 17180222
TI  - pH driven self-assembly of a ternary lanthanide luminescence complex: the sensing
      of anions using a beta-diketonate-Eu(III) displacement assay.
AB  - The synthesis and the photophysical evaluation of a novel pH dependent lanthanide
      luminescent self-assembly in water between a cyclen based europium complex and a
      beta-diketonate is described and its use as a luminescent sensor in displacement
      assays for anions such as acetate, bicarbonate and lactate, where the Eu(III)
      emission was quenched upon anion recognition.

PMID- 17180223
TI  - Disruption of the hexagonal networks of trimesic acid (benzene-1,3,5
      tricarboxylic acid, TMA) by acetic acid.
AB  - The single crystal X-ray structure of the acetic acid solvate of trimesic acid
      shows the complete disruption of the hydrogen-bonded hexagonal networks of TMA by
      bonding to an acetic acid molecule.

PMID- 17180224
TI  - Synthesis and structure of 1-D Na6 cluster chain with short Na-Na distance:
      organic like aromaticity in inorganic metal cluster.
AB  - A unique 1-D chain of sodium cluster containing (Na6) rings stabilized by a
      molybdenum containing metalloligand has been synthesized and characterized and
      the DFT calculations show striking resemblance in their aromatic behaviour with
      the corresponding hydrocarbon analogues.

PMID- 17180225
TI  - Sputtered Nb2O5 as an effective blocking layer at conducting glass and TiO2
      interfaces in ionic liquid-based dye-sensitized solar cells.
AB  - The thin Nb(2)O(5) layer works as a remarkable blocking layer when deposited by
      the rf magnetron sputtering method between fluorine-doped tin oxide and a
      mesoporous TiO(2) layer, improving open-circuit photovoltage (V(oc)) and fill
      factor (FF) with power conversion efficiency over 5.5% at 1 sun irradiation of
      the dye-sensitized TiO(2) solar cells using ionic liquid electrolytes.

PMID- 17180226
TI  - Trapping a pseudo-Hofmann rearrangement on a ruthenium cluster.
AB  - In the clusters [Ru3(micro(3)-NPPh(3))(micro(3)-OSiMe(3))(micro-X)(micro(C,O)
      OC[double bond]NPPh(3))(micro-CO)(CO)6] (X = NCO, 2; X = Cl, 3), which were
      prepared by a pyrolytic reaction of Ph(3)PNSiMe(3) with Ru(3)(CO)12, the ligands
      result from a cluster-mediated pseudo-Hofmann rearrangement involving the micro
      NCO, micro(C,O)-Ph(3)P[double bond]N-CO and micro(3)-NPPh(3) fragments.

PMID- 17180227
TI  - Uniform NH4TiOF3 mesocrystals prepared by an ambient temperature self-assembly
      process and their topotaxial conversion to anatase.
AB  - For the first time, we describe a simple, room-temperature surfactant-mediated
      route to inorganic mesocrystals of NH(4)TiOF(3) and their remarkable topotaxial
      conversion by washing or annealing to TiO(2) as anatase mesocrystals.

PMID- 17180228
TI  - Silver(I) N-heterocyclic carbene-bridged calix[4]arene analogues as efficient
      [60]fullerene receptors.
AB  - Two silver(I) N-heterocyclic carbene-bridged calix[4]arene analogues 4 and 5 were
      synthesized by a fragment-coupling approach; the preliminary inclusion properties
      of 5 with [60]fullerene shows that it is a novel efficient [60]fullerene
      fluorescent sensor.

PMID- 17180229
TI  - Oxidative desulfurization of dibenzothiophene with molecular oxygen using
      emulsion catalysis.
AB  - Dibenzothiophene (DBT) is oxidized to the corresponding sulfoxide and sulfone in
      an emulsion system (W/O) composed of polyoxometalate anion
      [C(18)H(37)N(CH(3))3](5)[PV(2)Mo(10)O(40)] as both the surfactant and catalyst,
      using molecular oxygen as the oxidant and aldehyde as the sacrificial agent under
      mild conditions.

PMID- 17180230
TI  - A rare ferromagnetic manganese(III) 'cube'.
AB  - A {Mn(III)4} distorted cube has been synthesized that possesses an S = 8 ground
      state and single-molecule magnetism behaviour.

PMID- 17180231
TI  - ESI mass spectrometry and X-ray diffraction studies of adducts between anticancer
      platinum drugs and hen egg white lysozyme.
AB  - The interactions of cisplatin and its analogues, transplatin, carboplatin and
      oxaliplatin, with hen egg white lysozyme were analysed through ESI mass
      spectrometry, and the resulting metallodrug-protein adducts identified; the X-ray
      crystal structure of the cisplatin lysozyme derivative, solved at 1.9 A
      resolution, reveals selective platination of imidazole Nepsilon of His15.

PMID- 17180232
TI  - Electrochemical synthesis of cobalt hydroxide films with tunable interlayer
      spacings.
AB  - An electrochemical synthetic condition is developed to produce cobalt hydroxide
      films with significantly increased basal spacings (d(001)>or= 25.0 A) by
      incorporating anionic surfactants (i.e. sodium dodecyl sulfate and 1
      hexadecanesulfonate) into the interlayer regions via electrodeposition.

PMID- 17180233
TI  - An efficient electrochemical synthesis of diamino-o-benzoquinone: mechanistic and
      kinetic evaluation of the reaction of azide ion with o-benzoquinone.
AB  - An efficient method for the synthesis of diamino-o-benzoquinone based on the
      Michael reaction of electrochemically generated o-benzoquinone with azide ion is
      described, as well as an estimation of the homogeneous rate constant (k(obs)) of
      the reaction of o-benzoquinone with azide ion by the digital-simulation method.

PMID- 17180235
TI  - Encapsulating fluorescein using adipic acid self-assembly on the surface of PPI-3
      dendrimer.
AB  - A water-soluble self-assembly has been formed by associating adipic acid
      molecules onto the surface of the third generation poly(propyleneimine) dendrimer
      and this system has been used to encapsulate fluorescein.

PMID- 17180234
TI  - Geometric self-sorting in DNA self-assembly.
AB  - Two types of DNA star motifs (tiles) can recognize and associate with like tiles
      to form 2D arrays but exclude unlike tiles even though the local interactions
      between any two tiles are exactly the same.

PMID- 17180236
TI  - Can the peroxosuccinate complex in the catalytic cycle of taurine/alpha
      ketoglutarate dioxygenase (TauD) act as an alternative oxidant?
AB  - Density functional theoretical studies on the catalytic properties of the
      peroxosuccinate intermediate in the catalytic cycle of taurine/alpha
      ketoglutarate dioxygenase suggest that it cannot act as a second oxidant.

PMID- 17180237
TI  - A simple NMR analysis of the protonation equilibrium that accompanies
      aminoglycoside recognition: dramatic alterations in the neomycin-B protonation
      state upon binding to a 23-mer RNA aptamer.
AB  - A complete characterisation of the protonation equilibrium that accompanies the
      molecular recognition of neomycin-B by a specific RNA receptor has been achieved
      by employing simple NMR measurements.

PMID- 17180238
TI  - glucoBox--a new carbohydrate-based bis(oxazoline) ligand. Synthesis and first
      application.
AB  - The synthesis of a new bis(oxazoline) ligand from D-glucosamine and its
      application in enantioselective copper(I) catalysed cyclopropanations of olefins
      is described.

PMID- 17180239
TI  - Double strand DNA cleavage with a binuclear iron complex.
AB  - Covalently linking two single strand DNA cleaving agents resulted in a new
      biomimetic binuclear iron complex capable of effecting oxidative double strand
      DNA cleavage.

PMID- 17180240
TI  - Tandem Staudinger-azaWittig mediated ring expansion: rapid access to new
      isofagomine-tetrahydroxyazepane hybrids.
AB  - New seven-membered iminosugars with potent and selective inhibition towards
      glycosidases have been prepared as 1-N-iminosugar homologues via a tandem
      Staudinger-azaWittig mediated ring expansion.

PMID- 17180241
TI  - Stereoselective stilbene epoxidation over supported gold-based catalysts.
AB  - The gold reference catalyst Au/TiO(2) exhibits high activity in the
      stereoselective epoxidation of trans-stilbene in methylcyclohexane in the
      presence of 5 mol% TBHP, by taking part in a chain reaction involving the
      activation of molecular oxygen by a radical produced from methylcyclohexane.

PMID- 17180242
TI  - The spin state of a charged non-IPR fullerene: the stable radical cation of
      Sc3N@C68.
AB  - In-situ ESR/UV-vis-NIR spectroelectrochemistry was implemented to probe the spin
      state of the radical cation of a non-IPR cluster-fullerene Sc(3)N@C(68), which
      represents the first study on the stable paramagnetic cation of an endohedral
      fullerene.

PMID- 17180243
TI  - {Ge10Si[Si(SiMe3)3]4(SiMe32)Me}-: a Ge10Si framework reveals a structural
      transition onto elemental germanium.
AB  - The reaction of the metastable high temperature molecule GeCl synthesized via a
      co-condensation technique with LiSi(SiMe(3))3 leads to a metalloid Ge(10)Si
      cluster compound, in which the arrangement of the germanium atoms can be seen as
      a cutout from the structure of elemental germanium.

PMID- 17180244
TI  - Photonic Boolean logic gates based on DNA aptamers.
AB  - We designed a pair of DNA-based logic gates that sense single-stranded DNAs and
      aptamer ligands to produce fluorescence outputs according to Boolean logic
      functions AND and OR.

PMID- 17180245
TI  - Trying to keep ahead of lice: a therapeutic challenge.
AB  - Pediculosis capitis, or head lice, is a world-wide public health concern
      affecting persons of all ages and socioeconomic backgrounds. It is caused by
      Pediculus humanus capitis, an obligate ectoparasite that lives on human hair and
      feeds on the blood from the skin. Upon diagnosis, treatment should be initiated,
      since established infestations with head lice generally do not spontaneously
      resolve. Chemical pediculicides are currently the standard treatment, however,
      issues of resistance have made it necessary to explore new alternatives. If an
      infestation is resistant to these drugs, then the physician should consider
      treating with an agent from a different class of pediculicides or, potentially,
      with newer nonpediculicides.

PMID- 17180246
TI  - Treatment of acne scarring.
AB  - Acne scarring is common but surprisingly difficult to treat. Scars can involve
      textural change in the superficial and deep dermis, and can also be associated
      with erythema, and less often, pigmentary change. In general, treatment of acne
      scarring is a multistep procedure. First, examination of the patient is necessary
      to classify the subtypes of scarring that are present. Then, the patient's
      primary concerns are elicited, and the patient is offered a menu of procedures
      that may address the various components of the scarring process. It is important
      to emphasize to the patient that acne scarring can be improved but never entirely
      reversed.

PMID- 17180247
TI  - DNA damage induces N-acetyltransferase NAT10 gene expression through
      transcriptional activation.
AB  - NAT10 (N-acetyltransferase 10) is a protein with histone acetylation activity and
      primarily identified to be involved in regulation of telomerase activity. The
      presented research shows its transcriptional activation by genotoxic agents and
      possible role in DNA damage. NAT10 mRNA could be markedly increased by using
      hydrogen peroxide (H2O2) or cisplatin in a dose- and time-dependent way, and the
      immunofluorescent staining revealed that the treatment of H2O2 or cisplatin
      induced focal accumulation of NAT10 protein in cellular nuclei. Both H2O2 and
      cisplatin could stimulate the transcriptional activity of the NAT10 promoter
      through the upstream sequences from -615 bp to +110 bp, with which some nuclear
      proteins interacted. Ectopic expression of NAT10 could enhance the number of
      survival cells in the presence of H2O2 or cisplatin. The above results suggested
      that NAT10 could be involved in DNA damage response and increased cellular
      resistance to genotoxicity.

PMID- 17180250
TI  - Artificial neural network: predicted vs observed survival in patients with
      colonic cancer.
AB  - PURPOSE: An Internet-web-based artificial neural network has been developed for
      practicing clinical oncologists and medical researchers as part of an ongoing
      program designed for the implementation of advanced neural networks for
      prognostic estimates and eventually for management/treatment decisions in
      individual patients with colonic cancer. METHODS: An interdisciplinary team of
      academic oncologists and physicists has configured and implemented a Partial
      Logistic Artificial Neural Network and trained it to predict cancer-related
      survival in patients with confirmed colorectal cancer by using a database (1,558
      patients) made available for the study by the Information & Statistics Division
      of National Health Service Scotland. The reliability of the trained network was
      evaluated against Kaplan-Meier observed survival plots of a random sample of 300
      patients not used in the training but forming part of the same data set. RESULTS:
      The predicted survival curves obtained as the output from the artificial neural
      network showed close agreement with observed actual survival rates of a cohort of
      300 patients with four grades of risk of dying from the cancer within five years
      of diagnosis. CONCLUSIONS: The web-based Partial Logistic Artificial Neural
      Network system accurately predicts survival after staging and treatment of
      colonic cancer. It can be made web-accessible where it is powerful enough to
      serve hundreds of users simultaneously.

PMID- 17180249
TI  - Loss of heterozygosity of the p53 gene and deregulated expression of its mRNA and
      protein in human brain tumors.
AB  - Tumor-specific alterations at the p53 gene locus were analyzed in 40 human brain
      tumor samples. Gliomas were more prevalent in young males and meningiomas in old
      females. Structural changes at the intron 1 region of the p53 gene were analyzed
      in these tumors by Southern blotting. Among the 40 tumors, 33 were informative
      and 21 of these (63.6%) informative cases showed loss of heterozygosity (LOH).
      This is the first report showing LOH at the intron 1 region of p53 gene in human
      brain tumors. The level of p53 mRNA, p53 protein and Ser 392 phosphorylated p53
      protein were also analyzed in all tumor samples. Normal sized p53 mRNA and
      protein were present in all the tumor samples; however, their levels were 1.5- to
      4-fold higher compared to the control suggesting deregulated p53 pathway in these
      tumors. No correlation was found between LOH status and the levels of p53 mRNA
      and protein. In all high-grade glioblastomas majority of the p53 protein existed
      as Ser 392 phosphorylated form as compared to low-grade gliomas. In addition, the
      percentage of Ser 392 phosphorylated form of p53 protein was lower in meningiomas
      and other brain tumor types irrespective of tumor grade. These results suggest
      involvement of Ser 392 phosphorylated form of p53 protein during the later stages
      of glioma development. These results also indicate that deregulation of p53 gene
      could occur at various steps in p53 pathway and suggest an overall deregulation
      of p53 gene in most brain tumor types.

PMID- 17180251
TI  - The effect of Crohn's disease on outcomes after restorative proctocolectomy.
AB  - PURPOSE: This study was designed to compare postoperative adverse events and
      functional outcomes after ileal pouch-anal anastomosis between patients with
      Crohn's disease and those with non-Crohn's disease diagnoses. METHODS: A
      literature search was performed to identify studies published between 1980 and
      2005 comparing outcomes of patients undergoing ileal pouch-anal anastomosis for
      Crohn's disease, ulcerative colitis, and indeterminate colitis. Random-effect,
      meta-analytical techniques were used and sensitivity analysis was performed.
      RESULTS: Ten studies comprising 3,103 patients (Crohn's disease=225; ulcerative
      colitis=2,711; indeterminate colitis=167) were included. Patients with Crohn's
      disease developed more anastomotic strictures than non-Crohn's disease diagnoses
      (odds ratio, 2.12; P=0.05) and experienced pouch failure more frequently than
      patients with ulcerative colitis (Crohn's disease vs. ulcerative colitis: 32 vs.
      4.8 percent, P<0.001; Crohn's disease vs. indeterminate colitis: 38 vs. 5
      percent, P<0.001). Urgency was more common in Crohn's disease compared with non
      Crohn's disease: 19 vs. 11 percent (P=0.02). Incontinence occurred more
      frequently in Crohn's disease compared with non-Crohn's disease patients: 19 vs.
      10 percent (odds ratio, 2.4; P=0.01). Twenty-four-hour stool frequency did not
      differ significantly between Crohn's disease, ulcerative colitis, or
      indeterminate colitis. Patients with isolated colonic Crohn's disease were not
      significantly at increased risk of postoperative complications or pouch failure
      (P=0.06). CONCLUSIONS: Patients with Crohn's disease undergoing ileal pouch-anal
      anastomosis should be appropriately counseled toward poorer functional outcomes
      and higher failure compared with non-Crohn's disease patients. It maybe possible
      to preoperatively select patients with isolated colonic Crohn's disease who may
      benefit from ileal pouch-anal anastomosis with acceptable adverse outcomes.

PMID- 17180248
TI  - Importance of the trans-sulfuration pathway in cancer prevention and promotion.
AB  - The trans-sulfuration pathway is a biochemical mechanism that links methionine
      metabolism to the biosynthesis of cellular redox-controlling molecules, like
      cysteine, glutathione, and taurine. While there is some knowledge about the
      metabolic intermediates and enzymes that participate in trans-sulfuration, little
      is known about the physiological importance of this mechanism. Deficiencies
      within the trans-sulfuration pathway induces (i) the generation of reactive
      species of oxygen (ROS) and halogens (RHS), (ii) homocyst(e)ine accumulation, and
      (iii) the synthesis of proinflammatory molecules by macrophages, and contribute
      to humans pathologies like atherosclerosis and tumor development. In this review
      we outline the role of this biochemical pathway in tumor development and analyze
      current findings on the role of trans-sulfuration in mammalian physiology. The
      potential relationship between chronic inflammation, and tumor and
      atherosclerotic development are discussed.

PMID- 17180253
TI  - Percutaneous gelfoam embolization of chronic enterocutaneous fistulas: report of
      three cases.
AB  - PURPOSE: A relatively simple radiologically guided method for the treatment of
      enterocutaneous fistula by gelfoam embolization is described. METHODS: Three
      cases of chronic enterocutaneous fistula are presented. In each case, a sheath
      was positioned with its tip at the enteric opening of the fistula. Gelfoam was
      injected to occlude the fistula at its enteric opening. RESULTS: In each case,
      there was successful closure of the fistula. CONCLUSIONS: Radiologically guided
      embolization with gelfoam is a safe, relatively simple procedure, which may be
      useful in the treatment of chronic enterocutaneous fistula.

PMID- 17180254
TI  - Adenocarcinoma of the small bowel arising from a previous strictureplasty for
      Crohn's disease: report of a case.
AB  - Small-bowel adenocarcinoma is an uncommon tumor, comprising<2 percent of all
      gastrointestinal tract malignancies. These tumors are known to occur in
      association with Crohn's disease. To date, there have been only two documented
      cases of adenocarcinoma arising at the site of previous strictureplasty reported
      in the literature. We report the third such case in a patient with no other
      premalignant conditions affecting the small bowel and question whether we may see
      an increasing trend in this type of presentation.

PMID- 17180255
TI  - Long-term results after stapled hemorrhoidopexy: high patient satisfaction
      despite frequent postoperative symptoms.
AB  - PURPOSE: Stapled hemorrhoidopexy has been demonstrated to be advantageous in the
      short term compared with the traditional techniques. We aimed to evaluate long
      term results after stapled hemorrhoidopexy and to assess patient satisfaction in
      association with postoperative hemorrhoidal symptoms. METHODS: This prospective
      study included 216 patients with Grade 2 or 3 hemorrhoids, who had stapled
      hemorrhoidopexy using the circular stapled technique. The results were evaluated
      by a standardized questionnaire at least 12 months after the operation. The
      primary end point was patient satisfaction; secondary end points included
      specific hemorrhoidal symptoms. RESULTS: Followup data were obtained for 193 of
      216 patients (89 percent) with a median follow-up of 28 (range, 12-53) months,
      most of whom (89 percent) were satisfied or very satisfied with the surgery. The
      main preoperative symptom was no longer present postoperatively in 66 percent of
      patients, was relieved in 28 percent, and had worsened in 2 percent.
      Postoperative complaints included symptoms of hemorrhoidal prolapse (24 percent
      of patients), anal bleeding (20 percent), anal pain (25 percent) fecal
      soiling/leakage (31 percent), fecal urgency (40 percent), and local discomfort
      (38 percent). Bivariate analysis showed significant associations between each of
      these symptoms and patient satisfaction. Nine patients (5 percent) were
      reoperated on during the follow-up period. CONCLUSIONS: Long-term patient
      satisfaction was high in most of patients after stapled hemorrhoidopexy for
      second-degree and third-degree hemorrhoids. However, an unsatisfactory outcome
      was significantly related to postoperative hemorrhoidal symptoms such as
      prolapse, fecal soiling/leakage, and new onset of fecal urgency.

PMID- 17180256
TI  - Prognostic groups in 1,676 patients with T3 rectal cancer treated without
      preoperative radiotherapy.
AB  - PURPOSE: The use of preoperative radiotherapy in patients with T3 tumors shows
      considerable variation among countries and institutions. The Norwegian guidelines
      have been very restrictive, limiting the indication to T4. This study was
      designed to identify subgroups of patients with T3 tumors with presumed high
      risks on adverse outcome and to use these results to reevaluate the national
      guidelines for preoperative radiotherapy. METHODS: This was a national cohort
      study of 2,460 patients with pT3 rectal adenocarcinoma, undergoing major surgery
      without preoperative radiotherapy from November 1993 to December 2002.
      Circumferential resection margin in millimeters was given for 1,676 patients.
      RESULTS: Multivariate analyses identified circumferential resection margin and
      nodal status as independent prognostic factors for local recurrence, metastases,
      and overall mortality. Analyses based on 12 combinations of N stage and
      circumferential resection margin showed that the estimated five-year rate of
      local recurrence increased from 11.1 percent (circumferential resection margin >3
      mm; N0) to 36.5 percent (circumferential resection margin < or =1 mm; N2). The
      rate of distant metastases increased from 18.5 to 77.7 percent and the five-year
      survival decreased from 68.6 to 25.7 percent, respectively. CONCLUSIONS: There is
      great variation in outcome for patients with T3 cancers, and the outcome is not
      acceptable for the groups of patients with circumferential resection margin <3 mm
      or involved lymph nodes. These groups should be considered for neoadjuvant
      therapy.

PMID- 17180257
TI  - Short-term outcome after laparoscopic or open restorative mesorectal excision for
      rectal cancer: a comparative cohort study.
AB  - PURPOSE: The laparoscopic approach to rectal cancer is still a controversial
      procedure. A comparative cohort study was conducted to assess short-term results
      of laparoscopic restorative mesorectal excision. METHODS: From January 1998 to
      December 2000, laparotomy was performed on all primary rectal cancer undergoing
      radical excision. From January 2002 to September 2004, all cases about to undergo
      radical excision were considered for laparoscopy. Patients with fixed tumor or
      T4, indications for synchronous hepatectomy, emergencies, and medical
      contraindications were not included. The study was based on the intention-to
      treat principle. RESULTS: Short-term outcome was compared between the laparoscopy
      group (n=104) and the laparotomy group (n=68). Demographic, general and tumor
      data, and rates of preoperative irradiation were comparable, as were surgical
      procedures and perioperative management. Hospital mortality (1 and 2.9 percent,
      P=0.33) and three-month overall morbidity (43.3 and 48.5 percent, P=0.49) were
      comparable between laparoscopy and laparotomy groups. Surgical complication rates
      were comparable (39.3 and 35.5 percent, P=0.58), but a significantly lower
      medical complication rate was observed in laparoscopy patients (8.7 and 20.6
      percent, P=0.025), mainly because this group had fewer respiratory complications.
      Hospital stay was shorter in laparoscopy patients (10 and 14 days, P<0.001).
      Oncologic quality criteria were comparable, in terms of number of lymph nodes,
      lateral and distal margins, and delivery of postoperative chemotherapy.
      CONCLUSIONS: The laparoscopic approach to restorative mesorectal excision for
      cancer does not increase postoperative morbidity or reduce oncologic quality. Our
      results suggest that the short-term outcome is probably improved with this
      procedure.

PMID- 17180259
TI  - Endoscopic full-thickness plication for the treatment of GERD: long-term
      multicenter results.
AB  - BACKGROUND: The purpose of the present study was to assess the long-term safety
      and durability of effect for endoscopic full-thickness plication for the
      treatment of symptomatic gastroesophageal reflux disease (GERD). The Plicator
      (NDO Surgical, Inc., Mansfield, MA) used delivers a transmural suture through the
      gastric cardia to restructure the antireflux barrier. Published reports have
      shown the Plicator procedure to be effective in reducing GERD symptoms and
      medication use at 1 year post-plication. METHODS: Twenty-nine patients with
      chronic heartburn requiring maintenance daily anti-secretory therapy were treated
      at five sites. Patients received a single full-thickness plication in the gastric
      cardia 1cm below the gastroesophageal junction (GE) junction. Re-treatments were
      not permitted. Patients were evaluated at baseline for GERD symptoms and
      medication use. Intermediate (12 month) and long-term subject follow-up (median
      follow-up: 36.4 months; range, 31.2-43.9 months) were completed to evaluate
      procedure safety and durability of effect. RESULTS: Twenty-nine patients
      completed the 12-month and 36-month follow-up. All procedure-related adverse
      events occurred acutely, and no new events were observed during extended follow
      up. At 36-months post-procedure, 57% (16/28) of baseline proton pump inhibitor
      (PPI)-dependent patients remained off daily PPI therapy. Treatment effect
      remained stable from 12- to 36-months, with 21/29 patients off daily PPI at 12
      months compared to 17/29 patients at 36-months. Median GERD- Health Related
      Quality of Life (HRQL) scores remained significantly improved at 36 months versus
      baseline off-meds scores (8 versus 19, p < 0.001). In addition, the proportion of
      patients achieving > or = 50% improvement in GERD-HRQL score was consistent from
      12 months (59%) to 36 months (55%). CONCLUSIONS: Endoscopic full-thickness
      plication can reduce GERD symptoms and medication use for at least 3-years post
      procedure. Treatment effect is stable from 1 to 3 years, and there are no long
      term procedural adverse effects.

PMID- 17180260
TI  - Developing a multimedia environment for customized teaching of an adrenalectomy.
AB  - We have developed a computer based simulation process which allows a surgical
      expert to create a customized operative environment. This virtual environment,
      the Toolkit for Illustration of Procedures in Surgery (3D TIPS), is deployed on a
      low-cost computer system and requires minimal training for the programmer. The
      learner can be engaged in training immediately and the educator can modify the
      system and annotate the procedure to highlight specific points using video clips,
      operative images, and the like. A laparoscopic adrenalectomy is presented as a
      proof of concept in the accompanying article.

PMID- 17180261
TI  - Pooled data analysis of laparoscopic vs. open ventral hernia repair: 14 years of
      patient data accrual.
AB  - BACKGROUND: The purpose of this study was to analyze the published perioperative
      results and outcomes of laparoscopic (LVHR) and open (OVHR) ventral hernia repair
      focusing on complications and hernia recurrences. METHODS: Data were compiled
      from all English-language reports of LVHR published from 1996 through January
      2006. Series with fewer than 20 cases of LVHR, insufficient details of
      complications, or those part of a larger series were excluded. Data were derived
      from 31 reports of LVHR alone (unpaired studies) and 14 that directly compared
      LVHR to OVHR (paired studies). Chi-squared analysis, Fisher's exact test, and two
      tailed t-test analysis were used. RESULTS: Forty-five published series were
      included, representing 5340 patients (4582 LVHR, 758 OVHR). In the pooled
      analysis (combined paired and unpaired studies), LVHR was associated with
      significantly fewer wound complications (3.8% vs. 16.8%, p < 0.0001), total
      complications (22.7% vs. 41.7%, p < 0.0001), hernia recurrences (4.3% vs. 12.1%,
      p < 0.0001), and a shorter length of stay (2.4 vs. 4.3 days, p = 0.0004). These
      outcomes maintained statistical significance when only the paired studies were
      analyzed. In the pooled analysis, LVHR was associated with fewer gastrointestinal
      (2.6% vs. 5.9%, p < 0.0001), pulmonary (0.6% vs. 1.7%, p = 0.0013), and
      miscellaneous (0.7% vs. 1.9%, p = 0.0011) complications, but a higher incidence
      of prolonged procedure site pain (1.96% vs. 0.92%, p = 0.0469); none of these
      outcomes was significant in the paired study analysis. No differences in cardiac,
      neurologic, septic, genitourinary, or thromboembolic complications were found.
      The mortality rate was 0.13% with LVHR and 0.26% with OVHR (p = NS). Trends
      toward larger hernia defects and larger mesh sizes were observed for LVHR.
      CONCLUSIONS: The published literature indicates fewer wound-related and overall
      complications and a lower rate of hernia recurrence for LVHR compared to OVHR.
      Further controlled trials are necessary to substantiate these findings and to
      assess the health care economic impact of this approach.

PMID- 17180262
TI  - Adverse effects of porcine small intestine submucosa (SIS) implants in
      experimental ventral hernia repair.

PMID- 17180264
TI  - Inclusion of an S-nitrosylating agent in the insufflating gas does not alter
      gastric activity in rats following pneumoperitoneum.
AB  - BACKGROUND: We have previously shown that mixing the S-nitrosylating agent ethyl
      nitrite with carbon dioxide can attenuate pneumoperitoneum-induced decreases in
      splanchnic blood flow, but it was unclear if this agent would alter gastric
      function. This question was answered using rats by assessing gastric emptying and
      gastrointestinal transit times following gavage with radioactive chromium.
      METHODS: There were five experimental groups: absolute control, anesthesia
      control, and carbon dioxide alone or with 100 or 300 parts per million ethyl
      nitrite. The period of insufflation was 1 h, and all animals were euthanized 6.5
      h after chromium administration. RESULTS: The mean amount of radioactivity
      remaining in the stomach ranged between 16% and 27% of the total administered;
      these differences were not statistically significant (p > 0.05). Modest
      differences in chromium distribution were identified in the gastrointestinal
      tract, but for all treatments, the peak amount of radioactivity was located in
      the distal portion. Location of the peak, expressed as a percentage of total
      tract length, varied between 70% and 85% (p = 0.366). CONCLUSIONS: This study
      found no adverse effect of ethyl nitrite on postoperative gastric emptying or
      gastrointestinal transit time following pneumoperitoneum. The findings support
      continued assessment of the clinical utility of ethyl nitrite in the setting of
      laparoscopic surgery.

PMID- 17180266
TI  - Laparoscopic suture gastropexy for gastric volvulus: a report of 14 cases.
AB  - BACKGROUND: Gastric volvulus is an uncommon condition that affects mostly older
      men. It occurs mainly as a result of congenital laxity of the stomach's
      attachments and might be accompanied by a diaphragmatic hernia. This sometimes
      causes the stomach to herniate into the thorax, giving rise to respiratory
      compromise. A patient can have acute or chronic disease. We present our series of
      14 patients who were managed with simple laparoscopic suture gastropexy. METHODS:
      We managed 14 patients with gastric volvulus during the past ten years; 2
      patients had primary type and 12 had secondary type gastric volvulus. Elective
      surgery was performed for the ten patients with chronic volvulus and emergency
      surgery was done for the four patients with acute volvulus. One of the patients
      with diaphragmatic hernia was six months pregnant and presented with acute
      symptoms. RESULTS: All patients recovered well from surgery, including the
      pregnant patient. The average hospital stay was five days; the pregnant woman was
      discharged on the sixth postoperative day. DISCUSSION: Symptoms of chronic
      gastric volvulus resemble those of reflux disease, whereas the acute condition is
      a surgical emergency. Gastric volvulus is a rare disease, so chances of
      laparoscopic management are also rare. There are also combined endoscopic and
      laparoscopic approaches for treatment; even percutaneous endoscopic gastrostomy
      has been tried with good results. In secondary volvulus, the diaphragmatic defect
      has to be repaired, preferably with mesh. Gastropexy is performed in all cases.
      CONCLUSION: Even though worldwide experience in laparoscopic surgery for gastric
      volvulus is limited, the results are encouraging. Based on our experience,
      laparoscopic management seems to be safe and feasible in acute and gastric
      volvulus.

PMID- 17180265
TI  - A laboratory study on anticipatory movement in laparoscopic surgery: a behavioral
      indicator for team collaboration.
AB  - BACKGROUND: To assess team collaboration in the context of laparoscopic surgery,
      laparoscopic cutting tasks performed by single operators and dyad teams were
      observed. Our previous work suggested that the anticipatory movement performed by
      a teammate may lead to a shorter total task time than for a single bimanual
      operator. This report further explores this phenomenon by quantifying the
      frequency of anticipatory movements and discussing their significance to team
      collaboration. METHODS: Subjects were required to reach, grasp, and cut a piece
      of thread using a laparoscopic grasper and scissors. The task was performed by
      either 8 individual subjects bimanually or 16 paired subjects unimanually (using
      their preferred hands). The performances were video recorded. The total task
      time, the time used for thread grasping and cutting, and the number of
      anticipatory movements were computed and compared between the single operator and
      the dyad team group. In this report, anticipatory movement is defined as
      movements of the scissors before the completion of grasping and holding the
      thread. RESULTS: Shorter durations of total task time were shown for the dyad
      than for the bimanual group. Anticipatory movements were counted significantly
      more often when the scissors were controlled by a teammate on the dyad team (96%)
      than when they were controlled by the preferred hand of the operator (45%). The
      number of anticipatory movements increased with practice, but no significant
      difference was shown among practice phases. CONCLUSION: Higher frequency of
      anticipatory movement was observed in the dyad team, which led to superior
      performance for team collaboration, as compared with that of the single operator.
      Performance of anticipatory movements in the dyad team was explained by a shared
      mental model, which postulates combined capacity for information processing among
      team members. Results have implications for surgical education, team training,
      and error prevention in the performance of laparoscopic surgery.

PMID- 17180263
TI  - The role of the surgeon in the evolution of flexible endoscopy.
AB  - Several cultures, including the Egyptians, Greeks, Romans, and Arabs, made
      attempts to view accessible human body cavities using a variety of instruments
      such as spatulas and specula. The first endoscope was created in 1806 when
      Phillip Bozzini, a German-born urologist, constructed the lichtleiter, which used
      concave mirrors to reflect candlelight through an open tube into the esophagus,
      bladder, or rectum. Maximilian Carl-Friedrich Nitze, another German urologist,
      produced the first usable cystoscope in 1877 by using series of lenses to
      increase magnification. He was also the first to place light inside the organ of
      interest to aid visualization. In 1880 Mikulicz made the first gastroscope using
      a system similar to Nitze's cystoscope. Modern endoscopy was born with the
      introduction of the fiberoptic endoscope in the late 1950s. Over the ensuing 50
      years endoscopy revolutionized many aspects of the surgeon's practice. Endoscopy
      can now be used to diagnose and often treat gastrointestinal cancer, hemorrhage,
      obstruction, and inflammatory conditions. This review was initiated by the SAGES
      Flexible Endoscopy Committee to chronicle the role of the surgeon in the
      development and introduction of flexible endoscopy into clinical practice,
      historically and in contemporary surgery. Flexible endoscopy evolved out of
      surgeons' need to overcome diagnostic and therapeutic challenges. There have been
      many recent technological advances that facilitate endoluminal therapies, and
      flexible endoscopy is now traversing new ground. Surgeons have been major
      contributors in the development of all aspects of endoscopy. There is a
      continually expanding list of therapeutic options available to patients. The
      difficult questions of which procedure, on which patient, and when can be
      answered best by the surgeon versed in endoscopic, laparoscopic, and open
      surgical techniques.

PMID- 17180267
TI  - A camera handler for Miccoli's minimally invasive video-assisted thyroidectomy
      and paratiroidectomy procedures.
AB  - BACKGROUND: Minimally invasive video-assisted thyroidectomy and paratiroidectomy
      (MIVAT/P) are surgical procedures performed with 5-mm cameras handled by a camera
      assistant. METHODS: The authors created a new camera handler for video-assisted
      neck surgery. It consists of a telescopic tripod device designed for mechanical
      handling of the camera, which is directly oriented by the operator even in solo
      surgery procedures. The camera is placed inside an O-shaped support, and moved by
      the operator himself for exploration and work on the surgical field. RESULTS:
      Thanks to this simple device, the camera holder provides a firm field and
      prevents blood stains in limited working spaces. CONCLUSIONS: The novel camera
      handler may be useful in either MIVAT/P or other simple laparoscopic procedures
      (i.e., cholecystectomy) for a steady handling of the camera, even in solo surgery
      procedures.

PMID- 17180268
TI  - Intraperitoneal aerosolization of bupivacaine reduces postoperative pain in
      laparoscopic surgery: a randomized prospective controlled double-blinded clinical
      trial.
AB  - BACKGROUND: Laparoscopic strategies for managing intraabdominal pathologies offer
      significant benefits compared with conventional approaches. Of interest are
      reports of decreased postoperative pain, resulting in shorter hospitalization and
      earlier return to normal activity. However, many patients still require strong
      analgesia postoperatively. This study analyzed the use of intraoperatively
      delivered aerosolized intraperitoneal bupivacaine and its ability to reduce
      postoperative pain. METHODS: For this study, 80 patients undergoing laparoscopic
      cholecystectomy were recruited and divided randomly into four groups: control (n
      = 20), aerosolized bupivacaine (n = 20), aerosolized normal saline (n = 20), and
      local bupivacaine in the bladder bed (n = 20). All the patients had standard
      preoperative, intraoperative, and postoperative care. Pain scores were recorded
      by the nursing staff in recovery, then 6, 12, and 24 h postoperatively using a
      standard 0 to 10 pain scoring scale. In addition, opiate consumption and oral
      analgesia were recorded. RESULTS: Aerosolized bupivacaine significantly reduced
      postoperative pain in comparison with all other treatments (p < 0.05). Injection
      of bupivacaine into the gallbladder bed did not result in a significant
      difference from the control condition. CONCLUSION: Aerosolized intraperitoneal
      local anesthetic is an effective method for controlling postoperative pain. It
      significantly helped to reduce opiate use and contributed to rapid mobilization,
      leading to short hospitalization and possible reduction in treatment cost.

PMID- 17180269
TI  - Laparoscopic Roux-en-Y gastric bypass versus laparoscopic vertical banded
      gastroplasty: results of a 2-year follow-up study.
AB  - BACKGROUND: The world's epidemic of obesity is responsible for the development of
      bariatric surgery in recent decades. The number of gastrointestinal surgeries
      performed annually for severe obesity (BMI > 40 kg/m2) in the United States has
      increased from about 16,000 in the early 1990s to about 103,000 in 2003. The
      surgical techniques can be classified as restrictive, malabsorptive, or mixed
      procedures. This article presents the results for 2 years of bariatric surgery in
      the authors' minimally invasive center and analyzes the results of the most used
      surgical techniques with regard to eating habits. METHODS: Between January 2002
      and January 2004, the authors attempted operations for morbid obesity in 110
      consecutive patients adequately selected by a multidisciplinary obesity unit.
      This represented 43% of all consultations for morbidly obese patients. The
      patients were classified as sweet eaters or non-sweet eaters. All sweet eaters
      underwent gastric bypass. The procedures included 70 Roux-en-Y gastric bypasses,
      39 Mason's vertical banded gastroplasties, and 1 combination of vertical
      gastroplasty with an antireflux procedure. Revision procedures were excluded.
      RESULTS: The mean age of the patients was 41.36 years (range, 23-67 years), and
      72.3% were female. The mean preoperative body mass index was 44.78 kg/m2 (range,
      34.75-70.16 kg/m2). The mean operating time was longer for gastric bypass than
      for the Mason procedure. Three patients required conversion to an open procedure
      (2.7%). The two operative techniques had the same efficacy in weight reduction.
      Early complications developed in 11 patients (10%), and late complications
      occurred in 9 patients (8.1%). The postoperative length of hospital stay averaged
      4.4 days (range, 1-47 days; median, 4 days), and was longer in the gastric bypass
      group. The mortality rate was zero. Data were available 2 years after surgery for
      101 of the 110 patients (91%). Most comorbid conditions resolved by 1 year after
      surgery regardless of the type of operation used. CONCLUSION: With zero mortality
      and low morbidity, bariatric surgery performed for adequately selected patients
      is the most effective therapeutic intervention for weight loss and subsequent
      amelioration or resolution of comorbidities. The patient's eating habits before
      surgery play an important role in the choice of the operative technique used.

PMID- 17180270
TI  - Surgical simulation: a current review.
AB  - BACKGROUND: Simulation tools offer the opportunity for the acquisition of
      surgical skill in the preclinical setting. Potential educational, safety, cost,
      and outcome benefits have brought increasing attention to this area in recent
      years. Utility in ongoing assessment and documentation of surgical skill, and in
      documenting proficiency and competency by standardized metrics, is another
      potential application of this technology. Significant work is yet to be done in
      validating simulation tools in the teaching of endoscopic, laparoscopic, and
      other surgical skills. Early data suggest face and construct validity, and the
      potential for clinical benefit, from simulation-based preclinical skills
      development. The purpose of this review is to highlight the status of simulation
      in surgical education, including available simulator options, and to briefly
      discuss the future impact of these modalities on surgical training.

PMID- 17180271
TI  - Outcome of laparoscopic colectomy for polyps not suitable for endoscopic
      resection.
AB  - BACKGROUND: Large colonic polyps or polyps that lie in anatomical locations that
      are difficult to access at endoscopy may not be suitable for endoscopic resection
      and therefore may require partial colectomy. This approach eradicates the polyp
      and allows an oncologic resection should the polyp prove to be malignant. The
      purpose of this study was to assess outcomes of a laparoscopic approach for the
      management of these polyps. METHODS: Patients referred for laparoscopic colectomy
      for colonic polyps were identified from the prospective colorectal laparoscopic
      surgery database. Demographics, operative details, and final pathology were
      reviewed. RESULTS: Fifty-one consecutive patients (27 male) with a mean age of 68
      +/- 11.4 years, ASA classification (1/2/3/4) of 0/21/27/3, and body mass index
      (BMI) of 26.5 +/- 4.9 were identified. Right (RHC) and left (LHC) colectomy was
      performed for 39 right and 12 left colonic polyps. Mean operating time (OT) was
      87 +/- 30 min (81 for RHC, 105 for LHC) and mean hospital stay was 3.1 +/- 1.9
      days. There were six complications (17.7%), including anastomotic leak (n = 1),
      small bowel obstruction (n = 2), abscess (n = 1), and exacerbation of preexisting
      medical conditions (n = 2). Four patients were readmitted (7.8%); one required CT
      scan-guided abscess drainage (1.9%) and two required reoperation (3.9%). Five
      patients (9.8%) were converted because of adhesions (n = 3), obesity (n = 1), and
      inability to identify the area that was tattooed at colonoscopy (n = 1). Mean
      polyp size was 3.1 cm, and pathology revealed tubular (n = 14), tubulovillous (n
      = 33) and villous adenoma (n = 2), pseudopolyp (n = 1), and prolapse of the
      appendix into the cecum mimicking an adenoma (n = 1). High-grade dysplasia was
      seen in four tubular (33%) and five tubulovillous adenomas (15.5%).
      Adenocarcinoma not identified at colonoscopy was found in 11 polyps (20%), 9
      tubulovillous (27.8%) and both villous adenomas (100%). CONCLUSIONS: Large
      colonic polyps unresectable at colonoscopy are associated with a high rate of
      unsuspected cancer. This requires a formal colectomy rather than transcolonic
      polypectomy. Laparoscopic colectomy offers safe and effective management of these
      polyps with the benefits of accelerated postoperative recovery.

PMID- 17180272
TI  - The introducer technique is the optimal method for placing percutaneous
      endoscopic gastrostomy tubes in head and neck cancer patients.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are often placed in
      head and neck cancer patients to provide nutritional support, but studies have
      found the complication rates to be higher than other subsets of patients who
      undergo PEG placement. Complication rates as high as 50% have been reported, with
      the bulk of these complications being PEG site issues (i.e., cellulitis, abscess,
      fascitis, and tumor implantation). Because the pull technique has been the
      primary technique used, the theory is that the transoral tube passage is the
      source of the complications in these patients. Alternatively, the introducer
      technique uses a transabdominal approach to place the device, avoiding any tube
      contamination by upper aerodigestive organisms or tumor cells. At our
      institution, this technique has been used exclusively for head and neck cancer
      patients and this article reports our experience. METHODS: One hundred forty-nine
      head and neck cancer patients who had a prophylactic PEG tube placed were
      reviewed from January 1, 1999 to December 31, 2003. The rates of placement
      success, morbidity, and complications were determined. RESULTS: Successful
      placement was achieved in 148 (99%) patients without any PEG-related deaths.
      Overall, 17 complications (11%) occurred, with only one major complication (0.7%)
      identified. PEG site infections were uncommon with only five cases (3.4%) and all
      were mild cellulitis. CONCLUSIONS: The introducer technique is the safest method
      for PEG tube placement in head and neck cancer patients. The overall rate of
      complications is low and PEG site infectious complications are rare. The
      introducer technique should be the method of choice for PEG tubes in head and
      neck cancer patients.

PMID- 17180274
TI  - Performance and ergonomic characteristics of expert surgeons using a face-mounted
      display during virtual reality-simulated laparoscopic surgery: an
      electromyographically based study.
AB  - BACKGROUND: Display positions for laparoscopy in current operating rooms may not
      be optimal for surgeon comfort or task performance, and face-mounted displays
      (FMDs) have been forwarded as a potential ergonomic solution. Little is known
      concerning expert use characteristics of these devices that might help define
      their role in future surgical care. The authors report the performance and
      ergonomic characterization of an FMD using virtual reality simulation technology
      to recreate the surgical environment. METHODS: An FMD was studied in short- and
      long-duration trials of validated virtual reality-simulated surgical tasks. For
      the short-duration phase 7, expert surgeons were familiarized with a task on a
      conventional monitor, then returned on two separate occasions to repeat the task
      with the FMD while digital photos were taken during task performance and at the
      end in a standardized fashion. For the long-duration phase 5, expert surgeons
      performed two separate trials with repetitive groups of validated tasks for a
      minimum of 30 min while electromyelogram and performance data were measured.
      Photos of their gaze angle during and at the end of the trial were taken.
      RESULTS: All the participants consistently assumed a gaze angle slightly below
      horizontal during task performance. Performance scores on the FMD did not differ
      from those obtained with a conventional display, and remained stable with
      repetitive task performance. No participant had electromyelogram signals that
      exceeded the established thresholds for fatigue, but some had values within the
      threshold range. CONCLUSION: The natural gaze angle during simulated surgery was
      consistently a bit below horizontal during rigorous virtual reality-simulated
      tasks. Performance was not compromised during expert surgeons' use of an FMD, nor
      did muscle fatigue characteristics arise under these conditions. The findings
      suggest that these devices may represent a viable alternative to conventional
      displays for minimally invasive surgery, but definition of specific roles
      requires further investigation.

PMID- 17180273
TI  - Surgical strategy for gastric gastrointestinal stromal tumors: laparoscopic vs.
      open resection.
AB  - BACKGROUND: Because wide resections and extensive lymphadenectomies are usually
      not required, the laparoscopic approach has been considered reasonable for
      gastrointestinal stromal tumors (GISTs) of gastric origin and has been reported
      with increased frequency. However, its long-term oncologic outcome has not been
      fully assessed. METHODS: We reviewed 67 consecutive patients who underwent
      laparoscopic (LAP) or traditional open (OPEN) resection of gastric GISTs from
      January 1993 to May 2004. RESULTS: There were 39 LAP and 28 OPEN cases. One LAP
      case was converted to open (2.6%). Patients in both groups had comparable
      backgrounds. Tumor location, size, and risk classification were similar. There
      was no difference in operating time and blood loss. Five patients (one in LAP and
      four in OPEN) showed recurrence and/or metastases after a median followup period
      of 26 months. Tumor enucleation resulted in a higher recurrence rate in both
      groups: one after three enucleations in LAP and two after six in OPEN. In cases
      with tumors that were larger than 5 cm, laparoscopic manipulation became
      technically challenging, although no recurrence was noted in this subgroup.
      Overall recurrence rate was comparable in the two groups. CONCLUSION:
      Laparoscopic surgery is oncologically justified for gastric GISTs, while its
      indication should be carefully discussed for cases with bulky and high-risk
      tumors. Tumor enucleations should be avoided whichever approach
      (open/laparoscopic) is selected.

PMID- 17180275
TI  - Laparoscopic sentinel node navigation achieved by infrared ray electronic
      endoscopy system in patients with gastric cancer.
AB  - BACKGROUND: The sentinel node (SN) concept has attracted considerable attention
      recently for the treatment of patients with early gastric cancer (EGC). This
      study evaluated the feasibility of laparoscopic SN navigation achieved by means
      of an infrared ray electronic endoscopy (IREE) system with indocyanine green
      (ICG) injection in patients with EGC. METHODS: Laparoscopic SN navigation was
      performed for 16 patients with preoperatively diagnosed EGC. After identification
      of SNs, routine laparoscopically assisted distal gastrectomy with lymphadenectomy
      was performed. Lymph nodes were examined histologically for metastasis by
      hematoxylin and eosin staining on one section of each node. RESULTS: One or more
      SNs and lymphatic basins were detected in all 16 patients. The average number of
      SNs detected was 2.9. Lymph node metastasis was found in 2 of the 16 patients
      (13%). In one of these two patients, lymph node metastasis was found in SNs. In
      the other patient, metastasis was found in a non-SN rather than a SN, but in the
      same lymphatic basin. The accuracy of this detection method was 94%, and there
      was one false-negative case. No adverse events occurred after injection of ICG.
      CONCLUSION: Laparoscopic SN navigation by means of IREE combined with ICG
      injection is feasible for patients undergoing laparoscopic surgery for EGC.

PMID- 17180276
TI  - Ringed silicon rubber attachment prevents laparoscopic surgeon's thumb.
AB  - BACKGROUND: This investigation, using the nerve conduction study, aimed to
      quantify the degree of laparoscopic surgeon's thumb, and to evaluate the effect
      of the ringed silicon rubber attachment (RSRA) developed by the authors. METHODS:
      For the study, 26 residents or students performed surgical tasks (grasping and
      dissecting) using both the laparoscopic forceps with RSRA and the conventional
      instrument. The paresthesia was evaluated with a severity score obtained by
      interview and measurement of sensory nerve conduction velocity (SCV). RESULTS:
      The mean severity score was 2.57 +/- 0.58 m/s for the conventional forceps and
      1.05 +/- 0.80 m/s for the forceps with RSRA (p < 0.01). For the grasping task
      with the conventional forceps, the mean SCV was 58.3 +/- 2.81 m/s before and 54.8
      +/- 2.83 m/s after the task (p < 0.01), whereas for the dissecting task, the
      corresponding values were 57.5 +/- 2.46 m/s and 56.1 +/- 2.93 m/s (p < 0.01). For
      the grasping task with the RSRA, the mean SCV was 57.1 +/- 3.33 m/s before and
      55.9 +/- 3.18 m/s after the task (p < 0.01), whereas for the dissecting task, the
      corresponding values were 55.7 +/- 4.59 m/s and 55.8 +/- 3.50 m/s (nonsignificant
      difference). CONCLUSIONS: Laparoscopic surgeon's thumb was induced by compression
      of the lateral digital nerve. The RSRA significantly reduced the degree of
      paresthesia.

PMID- 17180277
TI  - Prediction of recurrence after laparoscopic fundoplication for erosive reflux
      esophagitis based on anatomy-function-pathology (AFP) classification.
AB  - BACKGROUND: The usefulness of the anatomy-function-pathology (AFP) score was
      examined to evaluate its prediction of recurrence after laparoscopic
      fundoplication for erosive reflux esophagitis. METHODS: Of the patients
      undergoing laparoscopic fundoplication for erosive reflux esophagitis of Los
      Angeles classification grade A or higher from December 1994 to December 2004, 107
      who underwent preoperative barium esophagogram, pH monitoring, and endoscopy were
      selected as subjects. The AFP score was calculated by A, F, and P factor grades
      of the AFP classification. By comparing patients with and without recurrence, the
      usefulness of the AFP score for predicting recurrence was examined. RESULTS:
      Reflux esophagitis recurred in seven patients. No significant difference in age,
      sex, or A or F factor was observed between the groups, whereas a significant
      difference was observed in the P factor (p = 0.008). On the other hand, the mean
      AFP score in the recurrence group was 16.9 +/- 5.3, whereas that in the
      nonrecurrence group was 8.9 +/- 5.3 (p = 0.0021). Among the patients with a score
      of 17 points or more (n = 23), recurrence was found in 6 patients (26%). On the
      other hand, among the patients with a score lower than 17 points (n = 84),
      recurrence was found in 1 patient, but not in the remaining 83 patients (1%).
      Sensitivity was thus 85.7% (95% confidence interval [CI], 42.1-99.6), and
      specificity was 83% (95% CI, 74.2-89.8). The positive predictive value was 26.1%
      (95% CI, 10.2-48.4), and the negative predictive value was 98.8% (95% CI, 93.5
      99.9). Multiple logistic regression analysis was performed, and receiver
      operating characteristics curves were obtained. The area under the curve for the
      AFP score was 0.8457, whereas that for the P factor was 0.7907 (p = 0.0045),
      suggesting that the AFP score may more accurately predict recurrence than the P
      factor. CONCLUSION: The AFP score may be useful for predicting postoperative
      recurrence. If surgery is performed when the AFP score is lower than 17 points,
      the likelihood of postoperative recurrence is expected to be very low.

PMID- 17180278
TI  - Hartmann's gallbladder pouch revisited 60 years later.
AB  - BACKGROUND: Hartmann's gallbladder pouch was the subject of an article in The
      Lancet 60 years ago. It has regained new interest in view of laparoscopic
      cholecystectomy. However, different opinions exist with regard to its incidence
      and nature. To elucidate these discrepancies, a descriptive study was performed
      with regard to the incidence and morphology of Hartmann's pouch. METHODS:
      Gallbladders were obtained after elective laparoscopic cholecystectomy. In
      addition, gallbladders were obtained during routine postmortem examination. The
      gallbladders were divided in two groups: those with Hartmann's pouch and those
      without Hartmann's pouch. All the gallbladders were examined macroscopically and
      microscopically. Fisher's Exact Probability Test (p < 0.05, two-tailed) was used
      to analyze the data. RESULTS: A total of 98 gallbladders were examined: 49
      obtained after laparoscopic or open cholecystectomy and 49 obtained after
      postmortem examination. Among the gallbladders with Hartmann's pouch (n = 51),
      65% contained stones and 35% had no stones. Among the gallbladders without
      Hartmann's pouch, 43% contained stones and 57% had no stones. Macroscopically, in
      all the gallbladders with Hartmann's pouch, the pouch was observed to result from
      adhesions between the cystic duct and the neck of the gallbladder. After cleavage
      of these adhesions, the phenomenon of Hartmann's pouch was abolished in all
      cases. CONCLUSIONS: Hartmann's gallbladder pouch is a frequent but inconstant
      feature of normal and pathologic human gallbladders. There is a significant
      association between the presence of Hartmann's pouch and stones (p < 0.05).
      Adhesions between the cystic duct and the neck of the gallbladder are responsible
      for Hartmann's pouch. Consequently, Hartmann's gallbladder pouch is a morphologic
      rather than an anatomic entity.

PMID- 17180279
TI  - Optimal port placement and enhanced guidance in robotically assisted cardiac
      surgery.
AB  - BACKGROUND: Optimal port placement and enhanced guidance in robotically assisted
      cardiac surgery is required to improve preoperative planning and intraoperative
      navigation. METHODS: Offline optimal port placement is planned on a three
      dimensional virtual reconstruction of the patient's computed tomography scan.
      Using this data, an accurate in vivo port placement can be performed, which is
      achieved by augmented reality techniques superimposing virtual models of the
      thorax and the teleoperator arms on top of the real worldview. RESULTS: A new
      system incorporating both port placement planning and intraoperative navigation
      in robotically assisted minimally invasive heart surgery was established to aid
      the operative workflow. A significant reduction of operation time by improved
      planning and intraoperative support is anticipated. CONCLUSIONS: The enhanced
      intraoperative orientation possibilities may lead to further decrease in
      operation time and have the continuing ability to improve quality.

PMID- 17180280
TI  - A nontransfusional perioperative management regimen for patients with sickle cell
      disease undergoing laparoscopic cholecystectomy.
AB  - BACKGROUND: Patients with sickle cell disease (SCD) are at increased risk for
      cholelithiasis. Laparoscopic cholecystectomy is the most frequent general
      surgical operation performed for this group of patients. Acute chest syndrome
      (ACS) is the most common cause of postoperative death among SCD patients. This
      study aimed to evaluate the impact of a novel perioperative management regimen
      involving prophylactic continuous positive airways pressure (CPAP) ventilation
      and avoidance of preoperative blood transfusion on postoperative SCD-related
      complications after laparoscopic cholecystectomy. METHODS: A retrospective study
      included all SCD patients who underwent laparoscopic cholecystectomy since 1997
      at our institution. Medical notes were analyzed to assess the rates of
      postoperative complications in relation to the severity of SCD. RESULTS: A total
      of 13 patients were identified. There were no recorded episodes of acute painful
      crises and only one patient experienced an episode of ACS requiring protracted
      CPAP. CONCLUSION: Laparoscopic cholecystectomy can be safely performed for SCD
      patients without prior blood transfusion. A defined perioperative regimen
      including the use of routine postoperative prophylactic CPAP for these patients
      helps to reduce SCD-related postoperative complications such as ACS and painful
      vaso-occlusive crises.

PMID- 17180282
TI  - Integrating simulation into a surgical residency program: is voluntary
      participation effective?
AB  - OBJECTIVE: Surgical training programs nationwide are struggling with the
      integration of simulation training into their curriculum given the constraints of
      the 80-h work week. We examine the effectiveness of voluntary training in a
      simulation lab as part of the surgical curriculum. METHODS: The ProMIS simulator
      was introduced into the general surgery residency at Boston University Medical
      Center. All categorical residents (28) and non-categorical residents (23) were
      offered a 2-h training session and curriculum review. After the introductory
      session, time spent in the lab was encouraged, but voluntary. Use of the
      simulator was tracked for all residents. Participation in the simulation
      curriculum was defined as three or more uses of the simulator. After 3 months,
      all residents completed a survey regarding the simulation lab and their simulator
      usage. RESULTS: Twenty-six (93%) categorical residents and three (6%) non
      categorical residents completed the introductory simulator training session. Over
      a 3 month period, use of the simulator at least once was 31% among all eligible
      residents; 80% of postgraduate year (PGY)1, 40% of PGY2, 60% of PGY3, and 0% of
      PGY4 and PGY5. Four residents (14%) participated in the simulation curriculum.
      Overall, 70% of simulator usage was during working hours, and 30% was completed
      post-call or when the resident was off duty. Most residents agreed that the
      simulator was easy to use and that its use improved their operative skills, but
      they did not think it was a good substitute for actual operative experience.
      Reported reasons for not using the simulator included off-site rotation (44%), no
      time (30%), and no interest (11%). CONCLUSIONS: Voluntary use of a surgical
      simulation lab leads to minimal participation in a training curriculum.
      Participation should be mandatory if it is to be an effective part of a residency
      curriculum.

PMID- 17180281
TI  - Endoscopic ablation of intestinal metaplasia containing high-grade dysplasia in
      esophagectomy patients using a balloon-based ablation system.
AB  - BACKGROUND: This study aimed to determine the optimal treatment parameters for
      the ablation of intestinal metaplasia (IM) containing high-grade dysplasia (HGD)
      using a balloon-based ablation system for patients undergoing esophagectomy.
      METHODS: Immediately before esophagectomy, patients underwent ablation of
      circumferential segments of the esophagus containing IM-HGD using the HALO360
      system. The treatment settings were randomized to 10, 12, or 14 J/cm2 for two,
      three, or four applications. After esophagectomy, multiple sections from ablation
      zones were microscopically evaluated. Histologic end points included maximum
      ablation depth (histologic layer) and complete ablation of all IM-HGD (yes/no).
      RESULTS: Eight men with a mean age of 57 years (range, 45-71 years) were treated,
      and 10 treatment zones were created. There were no device-related adverse events.
      At resection, there was no evidence of a transmural thermal effect. Grossly,
      ablation zones were clearly demarcated sections of ablated epithelium. The
      maximum ablation depth was the lamina propria or muscularis mucosae. The highest
      energy (14 J/cm2, 4 applications) incurred edema in the superficial submucosa,
      but no submucosa ablation. Complete ablation of IM and HGD occurred in 9 of 10
      ablation zones (90%), defined as complete removal of the epithelium with only
      small foci of "ghost cells" representing nonviable, ablated IM-HGD and
      demonstrating loss of nuclei and cytoarchitectural derangement. One focal area of
      viable IM-HGD remained at the margin of one ablation zone (12 J/cm2, 2
      applications) because of incomplete overlap. CONCLUSION: Complete ablation of IM
      HGD without ablation of submucosa is possible using the HALO360 system. Ablation
      depth is dose related and limited to the muscularis mucosae. In one patient,
      small residual foci of IM-HGD at the edge of the ablation zone were attributable
      to incomplete overlap, which can be avoided. This study, together with
      nonesophagectomy IM-HGD trials currently underway, will identify the optimal
      treatment parameters for IM-HGD patients who would otherwise undergo
      esophagectomy or photodynamic therapy.

PMID- 17180283
TI  - Laparoscopic total extraperitoneal (TEP) inguinal hernia repair under epidural
      anesthesia: a detailed evaluation.
AB  - BACKGROUND: Laparoscopic total extraperitoneal (TEP) inguinal hernia repair is as
      efficacious as the open Lichtenstein procedure, can be learned with proper
      training, and causes less postoperative pain, better cosmesis, and earlier return
      to work. The one major factor preventing the widespread acceptance of TEP is the
      requirement for general anesthesia (GA). In contrast, open hernia is performed
      using local or regional anesthesia, thereby having the advantage of quicker
      recovery, decreased postoperative nausea and vomiting (PONV), fewer hemodyanamic
      changes, reduced metabolic responses to surgical stress, and better muscle
      relaxation. This study attempted to evaluate whether laparoscopic TEP can be
      performed under less invasive anesthesia, such as regional anesthesia, and to
      determine its feasibility and limitations METHODS: All total of 22 male patients
      were studied between January 2002 and March 2003 in a tertiary care referral
      hospital. Epidural anesthesia with 2% lignocaine with adrenaline (Adr) was given
      via a lumbar epidural catheter, achieving a sensory level of T6. The standard
      technique for TEP was followed, using three midline infraumbilical ports.
      RESULTS: Twenty-two patients (20 unilateral, 2 bilateral) underwent operation.
      The mean operating time was 67.8 +/- 18 (range, 40-110) min. All 22 cases were
      started with epidural anesthesia, 7 of which (31.9%) were converted to GA; the
      other 15 (68.1%) were completed under epidural anesthesia. All cases were
      successfully completed laparoscopically, and there were no conversions. There
      were no intraoperative complications. There was no significant difference between
      the cases conducted under epidural anesthesia (67.6 +/- 23 min) and those
      converted to GA (69.3 +/- 7.3 min). There was no statistically significant
      difference between the conversion rates of smaller versus larger hernias in this
      study (p value 0.22). A significant association of success of the procedure was
      seen with a sensory level of T6 and above (2/15 conversions to GA; i.e., 13.3%)
      and cases with a sensory level below T6 (5/7 converted; i.e., 71.4%) and adequate
      epidural catheter length (p = 0.015). Prevention and management of
      pneumoperitoneum and subsequent shoulder-tip pain was the key to preventing
      conversions (6 of 9 converted to GA; i.e., 67%; p = 0.006). There were no
      significant postoperative complications, and no recurrences were noted during a
      mean follow-up period of 29 months (range, 20-36 months). CONCLUSIONS: From the
      present study it is clear that TEP is possible under epidural anesthesia provided
      a minimal sensory level of T6 is achieved. To achieve that level, an appropriate
      higher site for catheter insertion and/or adequate intraepidural catheter length
      needs specific attention. Pneumoperitoneum, shoulder-tip pain, intraoperative
      straining, and inadequate preperitoneal space are factors whose interplay leads
      to conversion to GA. The size of the hernia is not related to pneumoperitoneum or
      conversion to GA.

PMID- 17180284
TI  - Interventional pancreaticojejunostomy after pancreatoduodenectomy.
AB  - BACKGROUND: Leakage from the pancreaticoenteric anastomosis after
      pancreatoduodenectomy (PD) is closely associated with intra-abdominal hemorrhage
      with ensuing high mortality. METHODS: Interventional pancreaticojejunostomy was
      performed in 10 patients with external drainage of pancreatic juice after two
      staged PD or leakage from pancreaticojejunostomy after PD. The jejunum was
      punctured using a 22-gauge needle into the pancreatic fistula during endoscopic
      observation of the jejunal lumen, followed by the insertion of two 0.35-inch
      guide-wires into the jejunum and pancreatic fistula. Finally, a stenting tube was
      placed between the jejunum and pancreatic fistula. RESULTS: No severe
      complications developed. Oral intake was instituted the following day in 8 of 10
      patients, and on the 7th day in the remaining two patients. CONCLUSION: This
      interventional procedure is considered to be safe and easy to perform, and in the
      future, it may permit a reduction in the number of second laparotomies in
      pancreatic fistula.

PMID- 17180285
TI  - Establishing a laparoscopic bariatric program in a safety net hospital.
AB  - BACKGROUND: Most laparoscopic bariatric programs are situated in a community- or
      university-based hospital. The authors have recently initiated a program at a
      safety net hospital. This investigation hypothesizes that a laparoscopic
      bariatric program can be established at a safety net hospital with good clinical
      and financial results. METHODS: A laparoscopic bariatric program was initiated
      December 2002 at a safety net hospital. The program included a dedicated
      operative suite, an operative team, a bariatric unit, and a clinical pathway. The
      data for all the patients who underwent laparoscopic gastric bypasses up to June
      2003 were analyzed. The patients were analyzed by type of insurance: government
      sponsored insurance (G) or commercial insurance (C). RESULTS: There were 104
      patients during this period. Their mean age was 40 years (range, 18-63 years),
      and their mean body mass index was 48 (range, 38-62). The median length of
      hospital stay was 2 days (mean, 3.9 days). Hypertension and diabetes were
      resolved for more than 80% of the patients. The average percentage of excess body
      weight loss was 73% after 1 year. There were no significant clinical differences
      between payor groups. The payor mix was 31% G and 69% C. The mean collection
      rates for hospital charges were 10% for G versus 53% for C (p < 0.0001).
      CONCLUSIONS: A laparoscopic bariatric program can be established in a safety net
      hospital with good clinical results. Findings showed that 1-year weight loss and
      comorbidity improvement/resolution compares favorably with those of other
      programs. Despite the overall poor payor mix of many safety net hospitals, a
      bariatric program can be established and can attract a high rate of commercially
      insured patients.

PMID- 17180286
TI  - Impact of endoscopic ultrasonography (EUS) on surgical decision-making in upper
      gastrointestinal tract cancer: an international multicenter study.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) is an integrated part of the
      pretherapeutic evaluation program for patients with upper gastrointestinal (GI)
      tract cancer. Whether the clinical impact of EUS differs between surgeons from
      different countries is unknown. The same applies to the potential clinical
      influence of EUS misinterpretations. The aim of this study was to evaluate the
      interobserver agreement on predefined treatment strategies between surgeons from
      four different countries, with and without EUS, and to evaluate the clinical
      consequences of EUS misinterpretations. METHODS: One hundred patients with upper
      GI tract cancer were randomly selected from all upper GI tract cancer patients
      treated at Odense University Hospital between 1997 and 2000. Based on patient
      records and EUS database results, a case story was created with and without the
      EUS result for each patient. Four surgeons were asked to select the relevant
      treatment strategy in each case, at first without knowledge of the EUS and
      thereafter with the EUS result available. Interobserver agreement and impact of
      EUS misinterpretations were evaluated using the actual final treatment of each
      patient as reference. RESULTS: Three of four or all four surgeons agreed on the
      same treatment strategy for nearly 60% of the patients with and without the EUS
      results. Treatment decisions were changed in 34% based on the EUS results, and
      the majority of these changes were toward nonsurgical and palliative treatments
      (85%). Interobserver agreement was relatively low, but overall EUS increased
      kappa values from 0.16 ("poor") to 0.33 ("fair"), thus indicating increased
      overall agreement after the EUS results were available. EUS conclusion regarding
      stage or resectability was wrong in 17% of the cases, but only one serious event
      would have been the clinical result of EUS misinterpretations. CONCLUSION:
      Despite being used in different ways by different surgeons, EUS did change
      patient management in one third of the cases. The impact of EUS
      misinterpretations seemed very low, and this study confirmed one of the strongest
      clinical possibilities of EUS, i.e., the ability to detect nonresectable cases.
      EUS is an important imaging modality for oncosurgeons from different countries.

PMID- 17180287
TI  - Outcomes analysis of laparoscopic resection of pancreatic neoplasms.
AB  - BACKGROUND: Experience with laparoscopic resection of pancreatic neoplasms
      remains limited. The purpose of this study is to critically analyze the
      indications for and outcomes after laparoscopic resection of pancreatic
      neoplasms. METHODS: The medical records of all patients undergoing laparoscopic
      resection of pancreatic neoplasms from July 2000 to February 2006 were reviewed.
      Data are expressed as mean +/- standard deviation. RESULTS: Laparoscopic
      pancreatic resection was performed in 22 patients (M:F, 8:14) with a mean age of
      56.3 +/- 15.1 years and mean body mass index (BMI) of 26.3 +/- 4.5 kg/m2. Nine
      patients had undergone previous intra-abdominal surgery. Indications for
      pancreatic resection were cyst (1), glucagonoma (1), gastrinoma (2), insulinoma
      (3), metastatic tumor (2), IPMT (4), nonfunctioning neuroendocrine tumor (3), and
      mucinous/serous cystadenoma (6). Mean tumor size was 2.4 +/- 1.6 cm. Laparoscopic
      distal pancreatectomy was attempted in 18 patients and completed in 17, and
      enucleation was performed in 4 patients. Laparoscopic ultrasound (n = 10) and a
      hand-assisted technique (n = 4) were utilized selectively. Mean operative time
      was 236 +/- 60 min and mean blood loss was 244 +/- 516 ml. There was one
      conversion to an open procedure because of bleeding from the splenic vein. The
      mean postoperative LOS was 4.5 +/- 2.0 days. Seven patients experienced a total
      of ten postoperative complications, including a urinary tract infection (UTI)
      (1), lower-extremity deep venous thrombosis (DVT) and pulmonary embolus (1),
      infected peripancreatic fluid collection (1), pancreatic pseudocyst (1), and
      pancreatic fistula (6). Five pancreatic fistulas were managed by percutaneous
      drainage. The reoperation rate was 4.5% and the overall pancreatic-related
      complication rate was 36.4%. One patient developed pancreatitis and a pseudocyst
      5 months postoperatively, which was managed successfully with a pancreatic duct
      stent. There was no 30-day mortality. CONCLUSIONS: Laparoscopic pancreatic
      resection is safe and feasible in selected patients with pancreatic neoplasms.
      With a pancreatic duct leak rate of 27%, this problem remains an area of
      development for the minimally invasive technique.

PMID- 17180288
TI  - Laparoscopic donor nephrectomy: intraoperative safety, immediate morbidity, and
      delayed complications with 500 cases.
AB  - BACKGROUND: Several large series of laparoscopic donor nephrectomy (LDN) have
      been published, largely focusing on immediate results and short-term
      complications. The aim of this study was to examine the results of LDN and
      collect medium-term and long-term donor followup. METHODS: We examined the
      results of two surgeons who performed 500 consecutive LDNs from 1996 to 2005.
      Prospective databases were reviewed for both donors and recipients to record
      demographics, medical history, intraoperative events, and complications. Patients
      were followed between 1 month and 9 years after surgery to assess for delayed
      complications, especially hypertension, renal insufficiency, incisional hernia,
      bowel obstruction, and chronic pain. RESULTS: Left kidneys were procured in 86.2%
      of cases. Mean operative time was 3.5 h, and warm ischemia time averaged 3.4 min.
      Hand-assistance was used in 13.8%, and conversion rate was 1.8%. Intraoperative
      complication rate was 5.8% and was predominantly bleeding (93.1%). Most (86.2%)
      of the operative complications occurred during the initial 150 cases of a
      surgeon, compared with 10.3% in the subsequent 150 cases (p = 0.003). Operative
      time decreased by 87 min after the initial 150 cases (p < 0.001). Immediate graft
      survival was 97.5%. Delayed graft function occurred in 3.0% of recipients, and
      acute tubular necrosis occurred in 7.0%. Thirty-day donor complication rate was
      9.8%. Mean donor creatinine was 1.24 on the first postoperative day, 1.27 at 2
      weeks, and 1.24 at 1 year. At a mean followup of 32.8 months, long-term donor
      complications consisted of 11 cases of hypertension, 9 cases of prolonged pain or
      paresthesia, 2 incisional hernias, 1 small bowel obstruction requiring
      laparoscopic lysis of adhesions, and 1 hydrocele requiring repair. CONCLUSIONS:
      LDN can be performed with acceptable immediate morbidity and excellent graft
      function. Operative time and complications decreased significantly after a
      surgeon performed 150 cases. Long-term complications were uncommon but included a
      likely underestimated incidence of hypertension.

PMID- 17180289
TI  - Laparoscopic distal pancreatectomy: results of a prospective non-randomized study
      from a tertiary center.
AB  - BACKGROUND: Though laparoscopic distal pancreatectomy for benign conditions was
      first described in the early 1990s, it has not become as popular as other
      laparoscopic surgeries. Published literature on this topic consists of several
      case reports and a handful of small series. We present our experience, which, to
      the best of our knowledge, is the largest series reported to date. METHODS: Since
      1998, 22 patients have undergone distal pancreatectomy at our institute. The
      technique of distal pancreatosplenectomy, as well as spleen-preserving distal
      pancreatectomy, is described. RESULTS: Four males and 18 females in the age range
      of 12-69 years underwent operation. Splenic preservation was possible in 7
      patients. The tumor diameter ranged from 2.1 cm to 7.4 cm. The mean operating
      time was 215 min. The mean length of incision required for specimen retrieval was
      3.4 cm. All patients were started on a liquid diet on the first postoperative
      day. The median hospital stay was 4 days. One patient developed a pancreatic
      fistula that was managed conservatively. At the end of an average follow-up of
      4.6 years, no recurrence has been reported. CONCLUSIONS: Laparoscopic distal
      pancreatectomy is a safe procedure, with minimal morbidity, rapid recovery, and
      short hospital stay. In appropriate cases, splenic preservation is feasible.

PMID- 17180290
TI  - Is there an optimal time for laparoscopic cholecystectomy in acute cholecystitis?
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) is safe in acute cholecystitis, but
      the exact timing remains ill-defined. This study evaluated the effect of timing
      of LC in patients with acute cholecystitis. METHODS: Prospective data from the
      hospital registry were reviewed. All patients admitted with acute cholecystitis
      from June 1994 to January 2004 were included in the cohort. RESULTS: Laparoscopic
      cholecystectomy was attempted in 1,967 patients during the study period; 80% were
      women, mean patient age was 44 years (range, 20-73 years). Of the 1,967 LC
      procedures, 1,675 were successful, and 292 were converted to an open procedure
      (14%). Mean operating time for LC was 1 h 44 min (SD +/- 50 min), versus 3 h 5
      min (SD +/- 79 min) when converted to an open procedure. Average postoperative
      length of stay was 1.89 days (+/- 2.47 days) for the laparoscopic group and 4.3
      days (+/- 2.2 days) for the conversion group. No clinically relevant differences
      regarding conversion rates, operative times, or postoperative length of stay were
      found between patients who were operated on within 48 h compared to those
      patients who were operated on post-admission days 3-7. CONCLUSIONS: The timing of
      laparoscopic cholecystectomy in patients with acute cholecystitis has no
      clinically relevant effect on conversion rates, operative times, or length of
      stay.

PMID- 17180291
TI  - Laparoscopic Witzel gastrostomy--a reappraised technique.
AB  - BACKGROUND: Laparoscopic gastrostomy is the best alternative for long-term
      enteral feeding when percutaneous endoscopic gastrostomy is not possible. The aim
      of the present study was to determine the feasibility, complications, adequacy of
      feeding support, and tolerability of laparoscopic Witzel gastrostomy (LWG) in
      head and neck cancer patients. The initial results and the results of extended
      follow-up were evaluated. METHODS: A consecutive series of 48 patients with
      stenotic head and neck or esophageal cancer were referred for laparoscopic
      gastrostomy. The patients consisted of 42 men and 6 women aged 36 to 82 years
      (mean, 54 years). After laparoscopic placement of a Foley catheter of 16 F into
      the stomach, a seromuscular tunnel 4 cm in length is created, embedding the
      catheter by interrupted sutures. Three stay sutures for gastropexy are fixed and
      tied on the abdominal skin at the end of the procedure. The mean duration of the
      procedure was 62.4 +/- 11 min (52-124 min). RESULTS: Laparoscopic Witzel
      gastrostomy could be performed successfully in all patients with aerodigestive
      cancer. None of the laparoscopic gastrostomy tube placement procedures was
      converted to an open surgery, and none of the 48 patients in this series died as
      a result of the laparoscopic procedure. All LWG complications (11%) were minor,
      consisting of superficial wound infections, balloon rupture, and chronic
      granulation. No major complications were encountered. The mean usage time of
      gastrostomy was 6.3 +/- 5.3 months. CONCLUSIONS: Current techniques of LWG could
      be an alternative to percutaneous endoscopic gastrostomy (PEG) for long-term
      enteral access, because it has proved to be safe and reproducible with relatively
      few complications.

PMID- 17180292
TI  - Transthoracic repair of Morgagni's hernia: a 20-year experience from open to
      video-assisted approach.
AB  - BACKGROUND: Foramen of Morgagni's hernia is an uncommon congenital diaphragmatic
      hernia. Repair is mostly performed through laparotomy. We prefer the
      transthoracic approach, which allows better and safer control during thoracic
      dissection, although it is considered more painful and related to greater
      morbidity. In recent years we introduced the transxiphoid hand-assisted
      videothoracoscopic approach, which combines the advantages of the thoracic route
      with a mini-invasive procedure facilitated by one hand inside the chest. METHODS:
      A retrospective review was performed over a 20-year period (1985-2005). Twenty
      two patients who had a foramen of Morgagni's hernia repaired were identified and
      relevant data were collected. Average age was 57 +/- 10 years and one half of the
      patients were asymptomatic. Chest roentgenograms, chest computerized tomography,
      and barium enema were used as diagnostic utilities. Posterolateral thoracotomy
      was performed in 17 (15 right-sided) patients, whereas in 5 (all right-sided) the
      defect was repaired by transxiphoid hand-assisted videothoracoscopy. Operative
      time, pain scored by visual analog scale, hospital stay, and cosmetic results by
      acceptance score were reviewed for every patient. RESULTS: Hernial sac was
      present in all cases and contained only omentum (n = 13), omentum plus transverse
      colon (n = 7), omentum plus transverse colon and small bowel (n = 2). In 6
      patients (2 videothoracoscopy) we repaired the large defects with polypropylene
      mesh. Videothoracoscopy achieved significant good results compared to thoracotomy
      in operative time (85 +/- 7.9 versus 110 +/- 11.3 min, p < 0.01), 24-h visual
      analog scale (3.5 +/- 1.1 versus 6.7 +/- 3.9, p < 0.01), hospital stay (2.6 +/-
      0.5 versus 6.4 +/- 1.2 days, p < 0.01), and acceptance score (4.3 +/- 0.5 versus
      3.1 +/- 0.8, p < 0.05). Postoperative course was always uneventful. Patients were
      followed for an average period of 58.6 +/- 14.7 and 109.7 +/- 43.5 months,
      respectively: no recurrences were found in any group. CONCLUSIONS: We believe
      that the transthoracic approach is a safe and effective method for repairing
      Morgagni's hernia. The videothoracoscopic approach is a promising alternative and
      it may be facilitated by introducing a hand inside the chest.

PMID- 17180293
TI  - A prospective case-matched comparison of clinical and financial outcomes of open
      versus laparoscopic colorectal resection.
AB  - BACKGROUND: We aimed to assess the clinical outcomes and costs associated with
      laparoscopic resection within an elective colorectal practice. METHOD: Over a 12
      month period data were prospectively collected on patients undergoing elective
      colorectal resection under the care of a single consultant surgeon. Thirty
      patients undergoing laparoscopic colorectal resection were case-matched by type
      of resection, disease process, and, where appropriate, cancer stage to patients
      having open surgery. A cost analysis was carried out incorporating cost of
      surgical bed stay, theater time, and specific equipment costs. RESULTS: In the 30
      patients having laparoscopic resection, a conversion rate of 13% was observed.
      Surgery was performed for colorectal cancer in 83% of patients, and 53% of
      resections were rectal. No significant differences were found in age (65 versus
      69 years, p = 0.415), BMI (27.4 versus 26.1, p = 0.527), POSSUM physiology score
      (16 versus 16.5, p = 0.102), American Society of Anesthesiologists (ASA) grade (2
      versus 2, p = 0.171), or length of theater time (160 min versus 160 min, p =
      0.233) between the laparoscopic and open patients. Hospital stay was reduced in
      the laparoscopic group (5 versus 9 days, p < 0.001). Average cost of surgical
      equipment used for a laparoscopic resection was greater than for open surgery
      (912.39 versus 276.41 pounds, p = 0.001). Cost of hospital stay was significantly
      less (1259.75 versus 2267.55 pounds, p < 0.001). Cost of operating room time was
      similar for the two groups (2066.63 versus 1945.07 pounds, p = 0.152). Overall no
      significant cost difference could be found between open and laparoscopic
      resection (4560.9 versus 4348.45 pounds, p = 0.976). More postoperative
      complications were seen in the open resection group (14 versus 4, p < 0.001).
      CONCLUSIONS: Intraoperative equipment costs are greater for laparoscopic
      resection than for open surgery. However, benefits can be seen in terms of
      quicker recovery and shorter hospital stay. Laparoscopic surgery is a financially
      viable alternative to open resection in selected patients.

PMID- 17180294
TI  - Laparoscopic colectomy for colon cancer: lymph node number and survival rates.

PMID- 17180295
TI  - New applications for endoscopy: the emerging field of endoluminal and
      transgastric bariatric surgery.
AB  - Endoluminal and transgastric procedures are evolving concepts that combine the
      skills and techniques of flexible endoscopy with minimally invasive surgery.
      Precisely how this technology and skill set will be applied in the field of
      general surgery is not yet known, but the treatment of obesity with an
      endoluminal or transgastric procedure holds great promise. As the demand for
      bariatric surgery increases, efforts will be directed toward developing less
      morbid and less costly treatment options that can provide substantial weight loss
      and resolution of comorbid conditions. Natural orifice bariatric procedures may
      include short-term weight loss in preparation for a definitive laparoscopic
      procedure, revisional procedures to reduce stoma or pouch size or repair
      fistulas, or primary therapy that provides durable weight loss. The latter
      application will undoubtedly appeal to patients and referring physicians if it
      can be performed as an outpatient procedure with significantly less morbidity
      than a laparoscopic procedure. Early preclinical and clinical work has been
      published in this area, but many technical obstacles must be overcome before a
      primary endoluminal or transgastric bariatric procedure can be offered. This
      article reviews the endoluminal and transgastric technology currently available,
      the endoluminal procedures currently performed, and the future of these
      technologies with respect to bariatric surgery.

PMID- 17180296
TI  - Diagnosis-related frequency of compulsory measures in 10 German psychiatric
      hospitals and correlates with hospital characteristics.
AB  - OBJECTIVE: To investigate the incidence of coercive measures in standard
      psychiatric care in different psychiatric hospitals. METHODS: We developed a
      common documentation of mechanical restraint, seclusion, and medication by
      coercion, and introduced it in 10 participating hospitals. We developed software
      able to process the data and to calculate four key indicators for routine
      clinical use. RESULTS: 9.5% of 36,690 cases treated in 2004 were exposed to
      coercive measures with the highest percentage among patients with organic
      psychiatric disorders (ICD-10 F0) (28.0%). Coercive measures were applied a mean
      5.4 times per case and lasted a mean 9.7 h each. The incidence and duration of
      coercive measures varied highly between different diagnostic groups and different
      hospitals. Use of detailed guidelines for seclusion and restraint was associated
      with a lower incidence of coercive measures. DISCUSSION: Data interpretation
      should consider numerous confounding factors such as case mix and hospital
      characteristics. Suggestions on how to cope with ethical and technical problems
      in the processing of large multi-site data sets in routine clinical use are made.

PMID- 17180297
TI  - Unusual presentation of triple A syndrome mimicking Sjogren's syndrome.
AB  - Triple A syndrome is a rare autosomal recessive disorder characterized by
      alacrima, achalasia, and adrenal insufficiency. Sjogren's syndrome (SS) is a
      chronic inflammatory disorder manifested primarily by diminished lacrimal and
      salivary gland secretions, resulting in symptoms of dry eyes and dry mouth, the
      so-called "sicca complex". However, a variety of other manifestations also can
      occur, which can be termed "nonexocrine manifestations". One of the frequent
      nonexocrine manifestations is dysphagia. In this paper, we present an unusual
      form of Triple A disease mimicking Sjogren's syndrome, which leads to a
      challenging diagnosis.

PMID- 17180299
TI  - Juvenile onset systemic sclerosis: a single center experience of 23 cases from
      Asia.
AB  - The aim of this paper was to study the spectrum of juvenile scleroderma (JSSc)
      seen at a tertiary care referral center in Asia. Retrospective analysis of case
      records of patients with systemic sclerosis, having age of onset less than 16
      years and seen at our hospital from 1988 to 2004, was done. Patients with linear
      scleroderma and morphea were excluded. There were 23 patients (19 girls, 4 boys)
      with median age of onset of 12 years (range 5-16 years). The median age at
      presentation was 17 years (range 10-34 years). The median time from first
      symptoms to presentation was 4 years (range 0.2-26 years). Among these, 14 had
      diffuse systemic sclerosis (DSSc), while 9 had limited scleroderma (LSSc). The
      clinical features seen at presentation in patients were: Raynaud's phenomenon in
      19, digital ulcers in 14, loss of finger tip pulp in 12, reflux in 8, dysphagia
      in 7, arthritis in 8, digital gangrene in 2, and pulmonary artery hypertension in
      1. Antinuclear antibody was positive in 15 out of 18 patients tested.
      Interstitial lung disease was seen in 15 patients, 6 of whom had diffuse disease.
      The median skin score was 22 (range 7-48) . One patient died of primary pulmonary
      hypertension within 1 year of onset of symptoms. At a mean follow-up of 34
      months, 14 patients were stable or had improvement in skin score or dyspnea on
      exertion. DSSc and LSSc in childhood have a clinical presentation similar to
      adult patients, with cardiopulmonary involvement being the major predictor of
      outcome. The short-term prognosis of JSSc is good.

PMID- 17180298
TI  - Oral and ocular/orbital manifestations of temporal arteritis: a disease with
      deceptive clinical symptoms and devastating consequences.
AB  - Temporal arteritis (TA) is a chronic, systemic vasculitis most often presenting
      with severe headaches localized in the temporal region, low-grade fever,
      anorexia, weight loss and generalized malaise. Besides these typical
      characteristics, a number of vague and non-specific oral and/or ocular symptoms
      may also be present. A search using Medline (1955-2006) was performed for unusual
      oral and ocular/orbital presentations of TA. A variety of oral and ocular/orbital
      manifestations associated with TA have been reported. These can mislead
      physicians, causing a delay in establishing a diagnosis and initiating treatment.
      Increased awareness is necessary for the prompt recognition of this potentially
      devastating disease. Particularly, dentists and ophthalmologists should include
      TA in their differential diagnosis, as they may be the first to deal with these
      patients.

PMID- 17180301
TI  - Influence of temperature on taste perception.
AB  - Daily experience tells us that temperature has a strong influence on how we
      taste. Despite the longstanding interest of many specialists in this aspect of
      taste, we are only starting to understand the molecular mechanisms underlying the
      temperature dependence of different taste modalities. Recent research has led to
      the identification of some strong thermosensitive molecules in the taste
      transduction pathway. The cold activation of the epithelial Na(+) channel and the
      heat activation of the taste variant of the vanilloid receptor (TRPV1t) may
      underlie the temperature dependence of salt responses. Heat activation of the
      transient receptor potential channel TRPM5 explains the enhancement of sweet
      taste perception by warm temperatures. Current development of methods to study
      taste cell physiology will help to determine the contribution of other
      temperature-sensitive events in the taste transduction pathways. Vice versa, the
      analysis of the thermodynamic properties of these events may assist to unveil the
      nature of several taste processes.

PMID- 17180300
TI  - Histidine-induced injury to cultured liver cells, effects of histidine
      derivatives and of iron chelators.
AB  - The amino acid histidine is an excellent buffer and is therefore included in
      several organ preservation solutions used in transplantation medicine. However,
      when used at concentrations as in these solutions, histidine has a marked
      injurious potential. Therefore, we here assessed the mechanism of histidine
      induced cell injury and searched for ways to use the buffering power of histidine
      but avoid histidine toxicity. When cultured hepatocytes were incubated in HTK
      solution or in modified Krebs-Henseleit buffer containing 198 mM L-histidine at
      37 degrees C, most cells lost viability within 3 h (LDH release 86 +/- 7% and 89
      +/- 5%, respectively). This injury was accompanied by marked lipid peroxidation,
      and was strongly inhibited by hypoxia, by the antioxidants trolox, butylated
      hydroxytoluene and N-acetylcysteine and by the membrane-permeable iron chelators
      2,2'-dipyridyl, 1,10-phenanthroline, LK 614, LK 616 and deferoxamine. Thus,
      histidine-induced cell injury appears to be mediated by an iron-dependent
      formation of reactive oxygen species. D-Histidine, imidazol and L-histidine
      methyl ester also elicited marked injury, while the N-substituted derivatives
      Nalpha-acetyl-L-histidine and tert-butyl-oxycarbonylhistidine and histidine
      containing dipeptides showed almost no toxicity. Histidine toxicity, its iron
      dependence and the superiority of Nalpha-acetyl-L-histidine were also evident
      during/after cold (4 degrees C) incubations. Therefore, we suggest the addition
      of iron chelators to histidine-containing solutions, and/or replacing histidine
      with Nalpha-acetyl-L-histidine in organ preservation solutions.

PMID- 17180302
TI  - Regulation of membrane trafficking and endocytosis by protein kinase C: emerging
      role of the pericentrion, a novel protein kinase C-dependent subset of recycling
      endosomes.
AB  - The protein kinase C (PKC) family of isoenzymes has been shown to regulate a
      variety of cellular processes, including receptor desensitization and
      internalization, and this has sparked interest in further delineation of the
      roles of specific isoforms of PKC in membrane trafficking and endocytosis. Recent
      studies have identified a novel translocation of PKC to a juxtanuclear
      compartment, the pericentrion, which is distinct from the Golgi complex but
      epicentered on the centrosome. Sustained activation of PKC (longer than 30 min)
      also results in sequestration of plasma membrane lipids and proteins to the same
      compartment, demonstrating a global effect on endocytic trafficking. This review
      summarizes these studies, particularly focusing on the characterization of the
      pericentrion as a distinct PKC-dependent subset of recycling endosomes. We also
      discuss emerging insights into a role for PKC as a central hub in regulating
      vesicular transport pathways throughout the cell, with implications for a wide
      range of pathobiologic processes, e.g. diabetes and abnormal neurotransmission or
      receptor desensitization.

PMID- 17180303
TI  - Olfactory groove meningiomas: functional outcome in a series treated
      microsurgically.
AB  - BACKGROUND: A systematic investigation of long-term follow-up results after
      microsurgical treatment of patients harbouring an olfactory groove meningioma,
      particularly with regard to postoperative olfactory and mental function, has
      rarely been performed. We reassessed a series of patients treated microsurgically
      for an olfactory groove meningioma in regard to clinical presentation, surgical
      approaches and long-term functional outcome. METHOD: Clinical, radiological and
      surgical data in a consecutive series of 56 patients suffering from olfactory
      groove meningioma were retrospectively reviewed. FINDINGS: Presenting symptoms of
      the 41 women and 15 men (mean age 51 years) were mental changes in 39.3%, visual
      impairment in 16.1% and anosmia in 14.3% of the patients. Preoperative
      neurological examination revealed deficits in olfaction in 71.7%, mental
      disturbances in 55.4% and reduced vision in 21.4% of the cases. The tumour was
      resected via a bifrontal craniotomy in 36, a pterional route in 13, a unilateral
      frontal approach in 4 and via a supraorbital approach in 3 patients. Extent of
      tumour resection according to Simpson's classification system was grade I in
      42.9% and grade II in 57.1% of the cases. After a mean follow-up period of 5.6
      years (range 1-13 years) by clinical examination and magnetic resonance imaging
      (MRI), 86.8% of the patients resumed normal life activity. Olfaction was
      preserved in 24.4% of patients in whom pre- and postoperative data were
      available. Mental and visual disturbances improved in 88 and 83.3% of cases,
      respectively. Five recurrences (8.9%) were observed and had to be reoperated.
      CONCLUSIONS: Frontal approaches allowed better resection of tumours with gross
      infiltration of the anterior cranial base, tumours extending into the ethmoids or
      nasal cavity and in cases with deep olfactory grooves. Preservation of olfaction
      should be attempted in patients with normal or reduced smelling preoperatively.

PMID- 17180305
TI  - Skull metastasis from hepatocellular carcinoma.
AB  - Metastasis to the skull frequently occurs in patients with lung, breast and
      prostate cancer. However, skull metastases from hepatocellular carcinoma (HCC)
      have been rarely reported. We review the literature on skull metastasis from HCC
      and report a case of a 46-year-old male, who was diagnosed as HCC and was
      operated on by trans-arterial embolization and lobectomy in Oct. 2004. He
      complained of a painless mass over the left frontal region for two months.
      Radiograph of the skull revealed an osteolytic mass about 4-5 cm in size over the
      left frontal region. A cranial computerized tomography demonstrated a destructive
      lesion with soft tissue mass over the left frontal region. A left frontal
      craniectomy was performed and tumor was totally removed. The histological
      diagnosis was cranial metastasis from HCC. Postoperative recovery was uneventful
      without any neurological deficits. Because of improved and advancing treatment
      for HCC, survival time for HCC has been lengthened and distant metastases will
      thus be found to increase. Early diagnosis is essential to treat the primary
      disease. Skull metastases from HCC should be considered as a differential
      diagnosis in patients with scalp subcutaneous mass and osteolytic defect on X-ray
      skull films.

PMID- 17180304
TI  - Spontaneous resolution of arachnoid cysts: review and features of an unusual
      case.
AB  - Most intra-cranial arachnoid cysts are quiescent and remain asymptomatic
      throughout life. Within the natural course of arachnoid cyst evolution,
      spontaneous resolution has been known to occur rarely, but its frequency is
      probably underestimated due to lack of systematic detection and long-term
      observation. We illustrate the spontaneous regression of arachnoid cysts with a
      patient which was conjointly diagnosed with an arachnoid cyst and a post
      traumatic epidural haematoma. Cyst regression was observed 16 months later, upon
      examination following a second benign cranial trauma. Mechanisms underlying the
      resolution of the arachnoid cyst are discussed.

PMID- 17180306
TI  - Acquired encephaloceles and epilepsy in osteopetrosis.
AB  - Osteopetrosis is a condition in which there is a defect in bone resorption by
      osteoclasts. With thickening of the skull and skull base, the cranial capacity
      becomes compromised and skull foramina gradually occlude, resulting in a wide
      range of neurological symptoms and signs. We present a case of autosomal dominant
      osteopetrosis with temporal lobe epilepsy and nasal obstruction due to acquired
      bifrontal encephaloceles associated with a decreased intracranial capacity.
      Neurosurgical reconstruction of the frontal skull base alleviated the symptoms of
      epilepsy and nasal obstruction.

PMID- 17180307
TI  - Decompressive hemicraniectomy in patients with subarachnoid hemorrhage and
      intractable intracranial hypertension.
AB  - BACKGROUND AND PURPOSE: To evaluate the outcome of patients with aneurysmal
      subarachnoid hemorrhage (aSAH) developing intractable intracranial hypertension
      and treated by decompressive hemicraniectomy (DHC). METHODS: Of 193 patients with
      aSAH 38 patients were treated with DHC after early aneurysm clipping. Indications
      for DHC were 1. Signs of brain swelling during aneurysm surgery (group 1: primary
      DHC). 2. Intracranial pressure- (ICP)-elevation and epidural, subdural or
      intracerebral hematoma after aneurysm surgery (group 2: secondary DHC due to
      hematoma) 3. Brain edema and elevated ICP without radiological signs of
      infarction (group 3: secondary DHC without infarction). 4. Brain edema and
      elevated ICP with radiological signs of infarction (group 4: secondary DHC with
      infarction). RESULTS: Thirty-one patients (81.6%) suffered from high grade aSAH
      Hunt & Hess 4-5. 21 belonged to group 1, five to group 2, six to group 3 and six
      to group 4. Of a total of 38 patients a good functional outcome according to
      Glasgow Outcome Score (GOS 4 & 5) could be reached in 52.6% of the cases. 26.3%
      survived severely disabled (GOS 3), no case suffered from a vegetative state (GOS
      2) but 21.1% died (GOS 1). After 12 months good functional outcome could be
      achieved in 52.4% of the cases in group 1, in 60% in group 2, in 83.3% in group 3
      and in 16.7% in group 4. CONCLUSIONS: In more than half of the patients with
      intractable intracranial hypertension after aSAH a good functional outcome could
      be achieved after DHC. Patients with progressive brain edema without radiological
      signs of infarction and those with hematoma may benefit most. The indication for
      DHC should be set restrictively if secondary infarcts are manifest.

PMID- 17180308
TI  - 20 years follow-up after the first microsurgical lumbar discectomies in Iceland.
AB  - BACKGROUND: Microsurgical discectomies are an established procedure in spinal
      surgery. This operating technique was first used in the Department of
      Neurosurgery in Iceland in 1981 and has become standard operative treatment for
      herniated lumbar discs. There is a great variability in outcome reports regarding
      recurrence rate and re-operation rate. Few articles are based on follow-up of
      more than 10 years. This article presents the results of a 20 years follow-up
      study. METHODS: A retrospective study of all patients undergoing microsurgical
      discectomy for herniated lumbar disc, from June 1, 1981 to December 31, 1984.
      Outcome, based on recurrence rate, return to work and patient satisfaction was
      determined by a self-evaluation questionnaire, phone interviews and patient
      medical records. FINDINGS: Of the 170 patients, 134 (78.8%) were included in the
      study (M:F, 58:42%). Preoperative symptoms: back pain with sciatica 108 (80.6%),
      sciatica 20 (14.9%), back pain 2 (1.5%). Mean follow-up time was 20.7 years (19.5
      22.8). Recurrence rate was 12.7%. 19 patients (14.2%) underwent a subsequent
      lumbar operation at a different level or side. A majority of patients 108 (80.6%)
      returned to previous level of work, 26 (19.4%) lost some or all working
      capabilities. Patient satisfaction was high, 91.1% reporting excellent (68.7%) or
      good (22.4%) results. 5.2% of patients rated the outcome fair and 3.7% poor.
      Women reported worse outcome than men, excellent M:F 74.7:60.7%, and poor
      7.1:1.3%. There was no significant difference in patient satisfaction in patients
      undergoing additional operations or those with recurrence of the herniated disc.
      CONCLUSIONS: Outcome was very good with 92.0% return to work and 91.1% patient
      satisfaction. The recurrence rate was 12.7% with a substantial number of cases
      occurring 10-20 years after operation. To conclude, microsurgical discectomies
      maintain a high success rate in the long-term.

PMID- 17180309
TI  - Tetraploid somatic hybrids of potato (Solanum tuberosum L.) obtained from diploid
      breeding lines.
AB  - Intraspecific somatic hybrids between 16 different diploid breeding lines of
      Solanum tuberosum L. were produced by PEG-induced fusion. Manually selected
      heterokaryons were cultured in a Millicells-CM using a post-fusion protoplast
      mixture. Plants were regenerated from calli derived from heterokaryons obtained
      from 10 out of 38 combinations of diploid lines. Of the tested putative somatic
      hybrids, 14.2% were diploid, 72.8% were tetraploid and 13% pentaploid. The DNA
      amplification pattern obtained with RAPD or semi-random primers confirmed that 6
      fusion combinations were hybrids. In most cases, the morphological traits were
      intermediate to those of the diploid fusion partners. About 23.0% of the tested
      somatic hybrids showed variation in their morphology. Of the tested somatic
      hybrids, 78.0% flowered and 86.0% tuberized. The cytoplasm of 9 diploid lines and
      6 somatic hybrid combinations was analysed. Two of the diploid lines had W/S
      chloroplasts and alpha or epsilon mitochondria; the remainder contained T
      chloroplasts and beta mitochondria. All the analysed somatic hybrids carried T
      chloroplasts and beta mitochondria.

PMID- 17180310
TI  - Genetic instability in the RAD51 and BRCA1 regions in breast cancer.
AB  - Breast cancer is the most prevalent cancer type in women. Accumulating evidence
      indicates that the fidelity of double-strand break repair in response to DNA
      damage is an important step in mammary neoplasias. The RAD51 and BRCA1 proteins
      are involved in the repair of double-strand DNA breaks by homologous
      recombination. In this study, we evaluated loss of heterozygosity (LOH) in the
      RAD51 and BRCA1 regions, and their association with breast cancer. The
      polymorphic markers D15S118, D15S214 and D15S1006 were the focus for RAD51, and
      D17S855 and D17S1323 for BRCA1. Genomic deletion detected by allelic loss varied
      according to the regions tested, and ranged from 29 to 46% of informative cases
      for the RAD51 region and from 38 to 42% of informative cases for the BRCA1
      region. 25% of breast cancer cases displayed LOH for at least one studied marker
      in the RAD51 region exclusively. On the other hand, 31% of breast cancer cases
      manifested LOH for at least one microsatellite marker concomitantly in the RAD51
      and BRCA1 regions. LOH in the RAD51 region, similarly as in the BRCA1 region,
      appeared to correlate with steroid receptor status. The obtained results indicate
      that alteration in the RAD51 region may contribute to the disturbances of DNA
      repair involving RAD51 and BRCA1 and thus enhance the risk of breast cancer
      development.

PMID- 17180311
TI  - Peripheral nervous system lesion syndromes and the mechanisms of their formation
      in connective tissue diseases.
AB  - Systemic rheumatological diseases are often accompanied by the development of
      central and peripheral nervous system pathology. Data providing evidence of the
      high incidence of peripheral nervous system lesions in systemic lupus
      erythematosus and systemic scleroderma are presented. These diseases in
      particular are characterized by polyneuropathies and tunnel syndromes. Our own
      observations, along with published data, revealed the following major
      pathogenetic mechanisms of peripheral nervous system lesions in diffuse
      connective tissue diseases - ischemic, immunological, and metabolic.
      Consideration of these mechanisms will lead to pathogenetically based treatment
      and improved therapeutic outcomes.

PMID- 17180312
TI  - Typology of post-traumatic stress disorder in children and adolescents.
AB  - Results obtained from clinical and psychopathological studies of 161 patients
      with post-traumatic stress disorder (PTSD) aged 3-18 years with symptom durations
      from one month to four years are presented. Four major clinical variants of the
      type of PTSD were identified in children and adolescents: insomniac( 34.8%),
      phobic (23.6%), psychopathic-like (21.7%), and asthenic-depressive (19.9%). These
      variants, differing in terms of course and prognosis, occurred at different
      frequencies in different age and ethnic groups; there were no gender-related
      differences.

PMID- 17180314
TI  - Effects of rapid and slow cooling on thermoregulatory reactions in hypertensive
      rats after administration of calcium.
AB  - Iontophoretic administration of calcium ions into the skin close to the
      application site of a cold stimulus decreased the threshold of thermoregulatory
      reactions in hypertensive rats to a greater extent than in normotensive control
      animals, which may be evidence that the tissues involved in thermoregulatory
      reactions to cold have a greater sensitivity to calcium in hypertensive rats. The
      initially earlier onset of vascular and metabolic reactions and the increase in
      the vascular reaction seen in hypertensive rats became more marked after
      administration of calcium. Treatment with calcium, increasing the vascular
      reaction to cooling, facilitates a more marked discrimination between hyper-and
      normotensive animals in terms of the appearance of the vasoconstrictor reactions
      of skin blood vessels in response to cold. The effects of the added calcium on
      cold-dependent reactions depended on the rate of cooling.

PMID- 17180313
TI  - Cognitive function and the emotional state of stroke patients on antihypertensive
      therapy.
AB  - Combined antihypertensive therapy based on 2.5-5 mg of cilazapril (an angiotensin
      converting enzyme inhibitor) to normalize arterial pressure (ABP) was studied in
      22 patients (12 male, 10 female) aged 49-74 years (mean 63 +/- 7 years) with
      stroke (18 patients) or transient ischemic attacks (three patients). Magnetic
      resonance tomography (MRT) including perfusion studies, along with
      neuropsychological studies and assessment of emotional status (Beck depression
      inventory, Spielberger anxiety scale), were performed before and after treatment.
      After six months of treatment, patients showed normalization of ABP (systolic
      pressure decreased from 154.7 +/- 12 to 128 +/- 23 mmHg, diastolic from 90.3 +/-
      9.6 to 79.4 +/- 23 mmHg). There were no side effects and no patient experienced
      stroke. MRT revealed no signs of new foci and there were no significant changes
      in brain blood flow. By the end of treatment, improvements in cognitive functions
      were noted on the Mini Mental State Examination, the 10-word memory test, the
      Boston naming test, or the Wisconsin card-sorting test, though there were no
      changes in the patients' emotional status.

PMID- 17180315
TI  - Characteristics of extinction of a conditioned passive avoidance reflex in mice
      with different levels of anxiety.
AB  - The relationship between the extinction of a conditioned passive avoidance reflex
      and the initial anxiety level was studied in mice. The time spent in the open
      arms of an elevated cross maze was used to classify the mice into high-,
      intermediate-and low-anxiety individuals. Each level of anxiety was found to
      correspond to a defined extinction dynamic. Highly anxious mice were
      characterized by the absence of extinction of the conditioned passive avoidance
      reflex and stability of good reproduction of the memory trace on testing to as
      long as 15 days. In intermediately anxious individuals, a deficit in performance
      of the avoidance reflex appeared from day 7 of extinction. In low-anxiety mice,
      memory trace reproduction deteriorated from test day 11.

PMID- 17180316
TI  - Behavior and measures of respiration in rabbits differing in terms of movement
      activity in an open field.
AB  - Analysis of the behavior of 19 Chinchilla rabbits the first time they were placed
      in an open field allowed them to be divided into three groups differing in terms
      of investigative movement activity (passive rabbits accounted for 37%, active for
      21%, and intermediate for 42%). On repeat placing in the open field, passive
      rabbits increased and active rabbits decreased their levels of activity.
      Correlations were found between the rabbits' behavior in the open field and the
      nature of their external respiration in the absence of movements in the comfort
      situation. Passive rabbits, as compared with intermediate and active animals,
      showed longer respiratory cycles, expirations, and breath holds in expiration.
      Animals with a predominance of right-hand turns in the open field showed shorter
      respiratory cycles and expirations than animals with a predominance of left-hand
      turns. These studies led to the conclusion that the characteristics of external
      respiration can serve as a predictive factor for the passive-defensive strategy
      of behavior in rabbits in emotionally negative situations.

PMID- 17180317
TI  - A possible mechanism of unilateral hippocampal stroke after bilateral occlusion
      of the common carotid arteries in rats with different types of behavior.
AB  - This article discusses the possible mechanisms of unilateral ischemic strokes
      arising in hippocampal field CA1 and the anterior dorsal nuclei of the thalamus
      after bilateral occlusion of the common carotid arteries in rats with different
      types of behavior.

PMID- 17180318
TI  - Effects of corticoliberin CRF(4-6) fragment on pain sensitivity in rats.
AB  - The effects of the tripeptide fragment corticoliberin CRF(4-6) (Pro-Pro-Ile) on
      pain sensitivity were studied in rats using the hotplate method. CRF(4-6) given
      centrally (6, 30, and 150 nmol/rat) had dose-dependent antinociceptive actions:
      the latent period of the paw-licking response increased by 7.4 +/- 1.4, 10.1 +/-
      1.5, and 16.7 +/- 4.2 sec from the control level of 10.2 +/- 0.9 sec. The
      durations of the effect were 30 min for CRF(4-6) at a dose of 6 nmol and 60 min
      for doses of 30 and 150 nmol of tripeptide. Administration of the corticoliberin
      antagonist alpha h CRF(9-41) (centrally, 6.5 nmol) 60 min before tripeptide
      completely blocked the antinociceptive effects of CRF(4-6) (6 nmol). Thus,
      corticoliberin receptors are involved in mediating the antinociceptive influence
      of CRF(4-6). It can be suggested that the tripeptide either directly interacts
      with corticoliberin receptors or modulates the activity of CRFergic neurons.

PMID- 17180319
TI  - Characteristics of behavior and stress reactivity of the hypophyseal
      adrenocortical system in rats with prenatal inhibition of testosterone
      metabolism.
AB  - The effects of administration of the aromatase blocker 1,4,6-androstatrien-3,17
      dione (ATD) to female rats in the last third of pregnancy on the stress
      reactivity of the hypophyseal-adrenocortical system (HACS), behavior in a novel
      environment (an open field), and anxiety in an elevated cross maze in their adult
      offspring of both genders were studied. Inhibition of testosterone aromatization
      in the brain during the prenatal period of development was found to lead to a
      decrease in the basal activity of the HACS in males and longer-lasting hormonal
      stress responses in animals of both genders. However, the intergender differences
      in the nature of the stress reactivity of the system in the experimental animals
      persisted. Prenatal administration of ATD also induced increases in the levels of
      anxiety and emotionality and the duration of grooming reactions in males and
      females and eliminated intergender differences between control males and
      experimental females in terms of measures of behavior in a new environment such
      as movement activity, duration of the freezing reaction, and grooming. These data
      led to the conclusion that impaired testosterone metabolism in the brain during
      the prenatal period of development induced by administration of the aromatase
      blocker leads to changes in the nature of the stress response of the HACS in
      adult male and female rats and impairs the formation of sexual dimorphism in
      anxiety levels and the extent of behavioral reactions to environmental novelty in
      females.

PMID- 17180320
TI  - Mechanisms of recognition of the outlines of "vanishing" optotypes.
AB  - The aim of the present work was to study the interaction between the optical
      properties of images of " disappearing" optotypes and their recognition
      thresholds. The "disappearing" optotypes were figures with complex outlines and
      had a unique property - they were close to the threshold of recognition and
      observation, which increases the accuracy of measurement of visual acuity and the
      subjects' attention to them. The recognition distances of "disappearing"
      optotypes were measured. A relationship was found between the recognition
      distance of "disappearing" optotypes and different optical density profiles on
      the one hand and the spatial and spatial frequency characteristics of the stimuli
      on the other. The decisive factor determining the threshold of recognition of
      optotypes in spatial frequency terms is its spatial frequency spectrum; that in
      spatial terms is the width of the black/white pair or black-white triad in the
      complex outline. Regardless of the shape of the optotype, one of the most
      important limiting factors was the concordance of this test with the scattering
      function of the subject's eye optics.

PMID- 17180321
TI  - Effects of alexithymia on the activity of the anterior and posterior areas of the
      cortex of the right hemisphere in positive and negative emotional activation.
AB  - The aim of the present work was to assess the effects of alexithymia (a
      psychoemotional disorder associated with difficulties in identifying and
      describing personal feelings) on regional activity in the cerebral cortex during
      positive and negative emotional activation in a non-clinical set of subjects. EEG
      (62-channel) recordings were made during presentation of special emotional video
      clips to alexithymics (17 subjects) and controls (27 subjects). Alexithymia was
      found to influence EEG activity in the theta-2, alpha-1, and alpha-2 ranges;
      alexithymics showed greater reactivity in the anterior and/or posterior areas of
      the cortex of the right hemisphere in all frequency ranges during watching of
      both positive and negative clips. The similarity of the responses of alexithymics
      in conditions of positive and negative emotional activation identifies the
      increase in emotional reactivity, independent of the sign of the incoming
      emotional information, as non-specific. This phenomenon may provide evidence of
      the need for recruiting additional cognitive resources for identifying emotional
      feelings in relation to the impairments of the symbolic perception of emotional
      information seen in alexithymics observed here.

PMID- 17180322
TI  - Effects of ionotropic glutamate receptor channel blockers on the development of
      pentylenetetrazol kindling in mice.
AB  - Experiments on mice were performed to study the ability of monocationic and
      dicationic adamantane and phenylcyclohexyl derivatives to prevent the development
      of kindling induced by i.p. administration of pentylenetetrazol (Corasol, 35
      mg/kg). The monocationic phenylcyclohexyl derivative IEM-1921 effectively slowed
      the development of kindling, this being seen over a wide range of doses (0.0001
      0.1 micromol/kg). A monocationic adamantane derivative (memantine), also a
      selective non-competitive blocker of NMDA receptors, produced a similar effect at
      doses 100 times higher. The anticonvulsive activity of the dicationic
      phenylcyclohexyl derivative IEM-1925, which could block both types of glutamate
      receptors, differed from the activity of the monocationic derivative by having a
      more complex dose-response relationship. Thus, the development of kindling was
      suppressed by essentially the same doses as needed for the monocation IEM-1921
      (0.001 micromol/kg). However, on reducing the dose by a factor of 10 (0.0001
      micromol/kg), IEM-1925 facilitated the development of kindling. This difference
      in the prophylactic activities of selective NMDA receptor blockers and substances
      able to block both NMDA and AMPA receptors provides evidence that the mechanism
      of kindling involves both types of ionotropic glutamate receptor and the effects
      of compounds depend not only on the ratio of the contributions of these
      receptors, but also on the kinetic characteristics of the blocking action.

PMID- 17180323
TI  - Transcription factor serum response factor is selectively involved in the
      mechanisms of long-term synapse-specific plasticity.
AB  - Our previous studies demonstrated that acquisition of nociceptive sensitization
      in common snails is accompanied by long-term facilitation of the responses of
      defensive behavior command neurons LPl1 and RPl1 to sensory stimuli, this being
      dependent on the processes of translation and transcription. The mechanism of
      induction of long-term synaptic facilitation at the sensory inputs of neurons
      from chemoreceptors on the head involves cAMP and the immediate early gene
      transcription factor C/EBP (CCAAT-enhancer-binding protein), while regulation of
      the other sensory input of neurons LPl1 and RPl1 - from mechanoreceptors on the
      head - depends on protein kinase C. The present report describes studies of the
      involvement of the transcription factor serum response factor (SRF) in the
      processes of the synapse-specific plasticity of neuron LPl1 during the
      acquisition of sensitization in snails. The acquisition of sensitization during
      intracellular administration of oligonucleotides specifically inhibiting SRF led
      to the selective suppression of synaptic facilitation in the responses of neuron
      LPl1 to tactile stimulation of the snail's head. Synaptic facilitation of
      responses to chemical stimulation of the head and tactile stimulation of the foot
      developed just as in neurons in control sensitized animals. The results were
      assessed in relation to a hypothesis postulating that synapse-specific plasticity
      on learning may occur because of selective neurochemical "projection" of synaptic
      connections to various genes within neurons.

PMID- 17180324
TI  - Acute appendicitis: diagnostic value of nonenhanced CT with selective use of
      contrast in routine clinical settings.
AB  - The purposes of this study were to determine the (1) frequency with which
      nonenhanced computed tomography (CT) (NECT) permits conclusive diagnosis of acute
      appendicitis, (2) accuracy of NECT when findings are conclusive, and (3) overall
      accuracy of a CT protocol consisting of NECT with selective use of contrast. Five
      hundred and thirty-six patients underwent a NECT protocol with selective use of
      contrast. Diagnostic accuracy was then determined separately for (1) patients
      with conclusive initial NECT, (2) patients with inconclusive initial NECT, and
      (3) all patients. NECT was conclusive on initial interpretation in 404/536
      patients and inconclusive in 132/536. Of 132 inconclusive studies, 126 were
      repeated with contrast (intravenous, oral or rectal). Sensitivity, specificity,
      and positive and negative predictive value for diagnosis of acute appendicitis
      were (1) 90%, 96.0%, 84.8%, and 97.4% in patients with conclusive NECT (n = 404);
      (2) 95.6%, 92.3%, 73%, and 99% in patients with inconclusive NECT followed by
      repeat CT with contrast; and (3) 91.3%, 95%, 82%, and 98% in all patients. The
      initial diagnosis of appendicitis may be made by NECT in 75% of patients, with
      contrast administration reserved for inconclusive NECT studies.

PMID- 17180326
TI  - Visual and automatic grading of coronary artery stenoses with 64-slice CT
      angiography in reference to invasive angiography.
AB  - The aim of this study was to assess the performance of a software tool for
      quantitative coronary artery analysis of computed tomography coronary angiography
      (CT-QCA) in comparison with invasive coronary angiography with quantitative
      analysis (CAG-QCA) as standard of reference. Two radiologists reviewed the CT
      angiography data sets (Siemens Sensation 64) of 25 patients, grading coronary
      artery stenoses visually and with a software tool (Circulation, Siemens). Twenty
      three data sets with sufficient image quality were included in the final
      analysis. CAG revealed a total of 30 wall irregularities and 28 stenoses, of
      which 17 were graded as moderate and nine as hemodynamically significant. CT-QCA
      showed a better agreement to CAG-QCA, with a systematic overestimation of the
      degree of stenosis of 6.1% and limits of agreement of +36.1% and -23.9; the
      correlation coefficient was 0.82 (p < 0.0001). Using CT-QCA, sensitivity,
      specificity, and positive and negative predictive value were 89%, 100%, 89%, and
      100%, respectively, for significant area stenoses greater than 75%. The positive
      predictive value for the visual assessment amounted to 53%. Interobserver
      variability between CT-QCA and visual assessment showed a kappa value of 0.72. In
      conclusion, software-supported CT-QCA makes it possible to quantify significant
      coronary artery stenoses automatically, with good agreement to CAG-QCA.

PMID- 17180325
TI  - Adrenal metastases: CT-guided and MR-thermometry-controlled laser-induced
      interstitial thermotherapy.
AB  - The aim of the study was to evaluate the feasibility, safety and effectiveness of
      CT-guided and MR-thermometry-controlled laser-induced interstitial thermotherapy
      (LITT) in adrenal metastases. Nine patients (seven male, two female; average age
      65.0 years; range 58.7-75.0 years) with nine unilateral adrenal metastases (mean
      diameter 4.3 cm) from primaries comprising colorectal carcinoma (n = 5), renal
      cell carcinoma (n = 1), oesophageal carcinoma (n = 1), carcinoid (n = 1), and
      hepatocellular carcinoma (n = 1) underwent CT-guided, MR-thermometry-controlled
      LITT using a 0.5 T MR unit. LITT was performed with an internally irrigated power
      laser application system with an Nd:YAG laser. A thermosensitive, fast low-angle
      shot 2D sequence was used for real-time monitoring. Follow-up studies were
      performed at 24 h and 3 months and, thereafter, at 6-month intervals (median 14
      months). All patients tolerated the procedure well under local anaesthesia. No
      complications occurred. Average number of laser applicators per tumour: 1.9
      (range 1-4); mean applied laser energy 33 kJ (range 15.3-94.6 kJ), mean diameter
      of the laser-induced coagulation necrosis 4.5 cm (range 2.5-7.5 cm). Complete
      ablation was achieved in seven lesions, verified by MR imaging; progression was
      detected in two lesions in the follow-up. The preliminary results suggest that CT
      guided, MR-thermometry-controlled LITT is a safe, minimally invasive and
      promising procedure for treating adrenal metastases.

PMID- 17180327
TI  - Bone marrow changes in beta-thalassemia major: quantitative MR imaging findings
      and correlation with iron stores.
AB  - The purpose of this study is to describe the MR imaging features of bone marrow
      in beta-thalassemia major and investigate their relation to ferritin, liver and
      spleen siderosis. Spinal bone marrow was prospectively assessed on abdominal MR
      studies of 40 transfused beta-thalassemic patients and 15 controls using T1-w,
      Pd, T2*-w Gradient Echo (GRE) and T1-w turbo Spin Echo (TSE) sequences. Signal
      intensity (SI) ratios of liver, spleen and bone marrow to paraspinous muscles
      (L/M, S/M, B/M respectively) and the respective T2 relaxation rates (1/T2) were
      calculated. Serum ferritin levels were recorded. Bone marrow hypointensity in at
      least T2*-w GRE sequence was noted in 29/40 (72.5%) patients. Eleven/40 patients
      exhibited normal B/M on all MR sequences. Five/40 patients had normal B/M and low
      L/M. B/M correlated with L/M in T1-w TSE sequence only (r = 0.471, p = 0.05). B/M
      correlated with S/M and mean ferritin values in all sequences (r > 0.489, p <
      0.01 and r > - 0.496, p < 0.03 respectively). Marrow 1/T2 did not correlate with
      ferritin values or liver and spleen 1/T2. B/M in transfused beta-thalassemic
      patients is related to splenic siderosis and ferritin levels. Although marrow is
      usually hypointense, it may occasionally display normal SI coexisting with liver
      hypointensity, a pattern typical of primary hemochromatosis.

PMID- 17180329
TI  - Tuberculous adenitis: comparison of CT and MRI findings with histopathological
      features.
AB  - Our aim was to investigate the relationship between the various histopathological
      features and the CT and MRI findings in routinely submitted histopathological
      specimens for the diagnosis of tuberculous lymphadenopathy. Twelve formalin
      fixed, paraffin-embedded tissue blocks from ten patients who were clinically
      suspected of having tuberculous lymphadenopathy were evaluated. We assessed the
      presence of histopathological features including granuloma formation, caseous
      necrosis, and presence of Langhans-type giant cells, calcifications, fibrosis or
      normal lymphoid tissue. We performed polymerase chain reaction (PCR)-based assay
      for mycobacterial DNA and Ziehl-Neelsen staining for acid-fast bacilli (AFB).
      Findings were compared with those of CT and MRI, including signal intensities on
      unenhanced MR images, lymph node homogeneity, attenuation values on contrast
      enhanced CT and enhancement patterns on MRI. Based on CT and MRI findings, four
      lymph node types could be defined: (1) homogeneous nodes, visible on both pre-
      and post-contrast images and corresponding histopathologically to granulation
      tissue without or with minimal caseation necrosis (n = 2); (2) heterogeneous
      nodes, showing heterogeneous enhancement patterns with central non-enhancing
      areas and corresponding to minor or moderate intranodal caseation/liquefaction
      necrosis (n = 3); (3) nodes showing peripheral rim enhancement and corresponding
      to moderate or extensive intranodal caseation/liquefaction necrosis (n = 5); (4)
      heterogeneous nodes showing intranodal hyperdensities on CT and hypointense areas
      on T1- and T2-weighted images and corresponding to fibrosis and calcifications (n
      = 2). On CT and MRI, the findings reflect different stages of the tuberculous
      process. Imaging findings depend on the presence and the degree of granuloma
      formation, caseation/liquefaction necrosis, fibrosis and calcifications.

PMID- 17180328
TI  - Characterization of hypoechoic focal hepatic lesions in patients with fatty
      liver: diagnostic performance and confidence of contrast-enhanced ultrasound.
AB  - The objective of this study was to assess the diagnostic performance of contrast
      enhanced ultrasound (CEUS) to characterize hypoechoic focal hepatic lesions
      (HFHL) in fatty liver (FL). A study group of 105 patients with FL and 105 HFHLs
      (52 malignant and 53 benign) underwent CEUS after SonoVue administration. Two
      blinded readers independently reviewed baseline ultrasound (US) and CEUS scans
      and classified each lesion as malignant or benign on a five-point scale of
      confidence, and recorded whether further imaging work-up was needed. Sensitivity,
      specificity, areas under the receiver operating characteristic (ROC) curve (A
      (z)), and interobserver agreement were calculated. We observed that the
      diagnostic confidence improved after reviewing CEUS scans for both readers (A
      (z)=0.706 and 0.999 and A (z)=0.665 and 0.990 at baseline US and CEUS,
      respectively; p<0.0001). Inter-reader agreement increased (weighted k=0.748 at
      baseline US vs. 0.882 at CEUS). For both readers, after CEUS, the occurrence of
      correctly characterized lesions increased (from 27/105 [27.5%] to 94/105 [89.5%],
      and from 19/105 [18.1%] to 93/105 [88.6%], respectively; p<0.0001) and the need
      for further imaging decreased (from 93/105 [88.6%] to 26/105 [24.8%], and from
      96/105 [91.4%] to 40/105 [38.1%], respectively; p<0.0001). We conclude that CEUS
      improves the diagnostic performance of radiologists in the characterization of
      HFHLs in FL and reduces the need for further imaging work-up.

PMID- 17180330
TI  - MRI investigation of normal fetal lung maturation using signal intensities on
      different imaging sequences.
AB  - To purpose of this paper is to study the relation between normal lung maturation
      signal and changes in intensity ratios (SIR) and to determine which magnetic
      resonance imaging sequence provides the strongest correlation of normal lung SIs
      with gestational age. 126 normal singleton pregnancies (20-37 weeks) were
      examined with a 1.5 Tesla unit. Mean SIs for lungs, liver, and gastric fluid were
      assessed on six different sequences, and SIRs of lung/liver (LLSIR) and
      lung/gastric fluid (LGSIR) were correlated with gestational age for each
      sequence. To evaluate the feasibility of SIRs in the prediction of the state of
      the lung maturity, accuracy of the predicted SIRs (D*) was measured by
      calculating relative residuals (D*-D)/D for each sequence. LLSIRs showed
      significant changes in every sequence (p<0.05), while LGSIRs only on two
      sequences. Significant differences were shown for the mean of absolute residuals
      for both LLSIRs (p<0.001) and for LGSIRs (p=0.003). Relative residuals of LLSIRs
      were significantly smaller on T1-weighted sequence, whereas they were
      significantly higher for LGSIRs on FLAIR sequence. Fetal liver seems to be
      adequate reference for the investigation of lung maturation. T1-weighted sequence
      was the most accurate for the measurement of the lung SIs; thus, we propose to
      determine LLSIR on T1-weighted sequence when evaluating lung development.

PMID- 17180331
TI  - Imaging findings predicting the outcome of cervical facet joint blocks.
AB  - To determine which cross-sectional imaging findings predict the short-term
      outcome of cervical facet joint blocks (FJB) and to evaluate the effect of
      combined intra-/periarticular versus periarticular injection on pain. Fifty facet
      joints in 37 patients were included in the study. Single, unilateral FJBs in 24
      patients, and bilateral single level FJBs in 13 patients were performed,
      respectively. In all patients, pain relief was assessed using a visual analogue
      scale. All computed tomography (CT) examinations were blindly reviewed by two
      radiologists. Osteoarthritis was rated using the Kellgren classification. The
      presence of combined intra-/periarticular vs. sole periarticular injection of
      contrast was evaluated. Kellgren Grades 0 (n=23), 1 (n=5), 2 (n=3), 3 (n=9), and
      4 (n=10) were found. Mean pain relief after injection was 35% (range: 0-100%).
      40% of all injections were combined intra-/periarticular. There was neither a
      statistically significant difference between pain relief and combined intra
      /periarticular versus sole periarticular injection (p=0.64) nor the grade of
      osteoarthritis (p=0.49). Pain relief after cervical FJBs does not correlate with
      morphologic alterations seen on CT. Periarticular FJBs are not less successful
      than combined intra-/periarticular FJBs.

PMID- 17180332
TI  - An unusual case of elevated liver enzymes (2006: 10b). Hepatic necrosis following
      HELLP syndrome.
AB  - HELLP syndrome is a form of severe pre-eclampsia with multisystem involvement.
      Laboratory markers include haemolysis (H), elevated liver enzymes (EL), and low
      platelets (LP). We present a patient to our institution with HELLP syndrome
      complicated by liver necrosis. The patient underwent urgent Caesarian section
      prior to transfer.

PMID- 17180333
TI  - Additional value of integrated PET-CT in the detection and characterization of
      lung metastases: correlation with CT alone and PET alone.
AB  - The purpose was evaluating retrospectively the additional value of integrated
      positron emission tomography (PET) and computed tomography (CT) in the detection
      of pulmonary metastases in comparison with CT and PET alone. Fifty-six lung
      nodules, divided into three groups according their size, detected in 24
      consecutive patients with a known primary tumor were retrospectively evaluated
      with integrated PET-CT, CT and PET. The nature of these nodules was determined by
      either histopathology or a follow-up of at least 6 months. The CT and PET images
      of the integrated PET-CT were evaluated separately by a radiologist and a nuclear
      medicine physician, the integrated PET-CT images were evaluated by a chest
      radiologist and nuclear medicine physician in consensus. The investigators were
      asked to search lung nodules and to determine whether these nodules were
      metastases or not. Sensitivity and accuracy for CT, PET and integrated PET-CT for
      characterization of all pulmonary nodules were, respectively: 100%, 90%, 100% and
      57%, 55%, 55%. There was no significant difference in the characterization of
      pulmonary nodules between integrated PET-CT and CT alone (P=1.000) and PET alone
      (P=0.1306). An accurate evaluation is only possible for lesions larger than 1 cm.

PMID- 17180334
TI  - Ceruminous adenoma mimicking furunculosis in the external auditory canal.
AB  - Tumors arising from the ceruminous glands are very rare. Herein, we report a case
      of ceruminous adenoma mimicking furunculosis in the external auditory canal
      (EAC), along with a discussion of the various pathological types and a review of
      their management.

PMID- 17180336
TI  - The potentiometric behavior of polymer-supported metallophthalocyanines used as
      anion-selective electrodes.
AB  - Liquid polymer membrane electrodes based on nickel and manganese phthalocyanines
      were examined for use as anion-selective electrodes. The electrodes were prepared
      by incorporating the ionophores into plasticized poly(vinyl chloride) membranes,
      which were directly coated onto the surfaces of graphite electrodes. The
      resulting electrodes demonstrate near-Nernstian responses over a wide linear
      range of perchlorate anion (5 x 10(-7) to 1 x 10(-1) M). The electrodes have a
      fast response time, submicromolar detection limits (5 x 10(-7) M perchlorate),
      and could be used over a wide pH range of 3.5-10. The influences of lipophilic
      cationic and anionic additives on the response properties of the electrodes were
      investigated. The proposed sensors revealed high selectivity for perchlorate over
      a number of common inorganic and organic anions. The highest selectivity was
      observed for the electrode based on manganese phthalocyanine in the presence of
      the lipophilic anionic additive sodium tetrakis[3,5
      bis(trifluoromethyl)phenyl]borate. Application of the electrodes to determine
      perchlorate in tap water and human urine is also reported.

PMID- 17180337
TI  - Electrochemical study of brucine on an electrode modified with magnetic carbon
      coated nickel nanoparticles.
AB  - A novel type of glassy carbon electrode modified with magnetic carbon-coated
      nickel nanoparticles (C-Ni/GCE) was fabricated and the electrochemical properties
      of brucine were studied using it. The carbon-coated nickel nanoparticles showed
      excellent electrocatalytic activity for the redox of brucine and an enhanced
      electron transfer rate. The electrochemical behavior of brucine on the C-Ni/GCE
      was explored by cyclic voltammetry (CV), and a redox mechanism for brucine was
      proposed. A series of electrochemical parameters were calculated for brucine by
      CV and controlled-potential electrolysis. The C-Ni/GCE showed good sensitivity,
      selectivity and stability, and was applied to determine the concentration of
      brucine. The differential pulse voltammetry (DPV) response of the C-Ni/GCE showed
      that the catalytic current was linear with the concentration of brucine in the
      range of 4.7 x 10(-8) to 2.4 x 10(-4) mol l(-1), with a correlation coefficient
      of 0.998. The detection limit was 1.4 x 10(-8) mol l(-1).

PMID- 17180335
TI  - Effect of cocaine self-administration on striatal PKA-regulated signaling in male
      and female rats.
AB  - RATIONALE: Chronic cocaine produces changes in the dopamine (DA)/D1/cAMP/protein
      kinase A (PKA)-regulated signaling pathway that may underlie the development of
      addiction. OBJECTIVE: Given sex differences in the progression to cocaine
      addiction, we examined the possibility that the PKA pathway is differentially
      activated by cocaine in male and female rats. MATERIALS AND METHODS: Rats were
      given 24-h access to cocaine (1.5 mg/kg) or saline for 7 days under a discrete
      trial procedure (four trials per hour). Rats were then retested on responding for
      cocaine under a progressive-ratio schedule after either 0 (no-delay retest) or 10
      (10-day-delay retest) days of abstinence. Markers of PKA-regulated signaling in
      the striatum and nucleus accumbens were evaluated by Western blotting, including
      phosphorylation of DA and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) at
      Thr 34 and glutamate receptor 1 (GluR1) at Ser 845. RESULTS: Compared to males,
      females had higher levels of DARPP-32 phosphorylated at the PKA site in the
      striatum. Increased phosphorylation of DARPP-32 at the PKA site was also seen in
      the nucleus accumbens of females compared to males, particularly among controls
      and rats tested after a 10-day abstinence period. DARPP-32 phosphorylation was
      also increased as a consequence of cocaine when tested after a 0-day abstinence
      period in male rats but not female rats. CONCLUSION: These findings indicate sex
      differences in PKA-regulated signaling in drug-naive controls. Furthermore, these
      data suggest that regulation of PKA signaling by cocaine is differentially
      influenced in male and female rats as a consequence of cocaine exposure and
      cocaine abstinence period.

PMID- 17180338
TI  - An adaptive strategy for selecting representative calibration samples in the
      continuous wavelet domain for near-infrared spectral analysis.
AB  - Sample selection is often used to improve the cost-effectiveness of near-infrared
      (NIR) spectral analysis. When raw NIR spectra are used, however, it is not easy
      to select appropriate samples, because of background interference and noise. In
      this paper, a novel adaptive strategy based on selection of representative NIR
      spectra in the continuous wavelet transform (CWT) domain is described. After
      pretreatment with the CWT, an extension of the Kennard-Stone (EKS) algorithm was
      used to adaptively select the most representative NIR spectra, which were then
      submitted to expensive chemical measurement and multivariate calibration. With
      the samples selected, a PLS model was finally built for prediction. It is of
      great interest to find that selection of representative samples in the CWT
      domain, rather than raw spectra, not only effectively eliminates background
      interference and noise but also further reduces the number of samples required
      for a good calibration, resulting in a high-quality regression model that is
      similar to the model obtained by use of all the samples. The results indicate
      that the proposed method can effectively enhance the cost-effectiveness of NIR
      spectral analysis. The strategy proposed here can also be applied to different
      analytical data for multivariate calibration.

PMID- 17180340
TI  - Some new trends in the ionoluminescence of minerals.
AB  - Ionoluminescence (IL) has mainly been used to detect impurities or defects inside
      synthetic materials. This paper gives a summary of new applications of IL to
      natural minerals that might be found in ancient pieces of jewellery or decorative
      artefacts (affreschi, stucchi, mosaics). Some relevant examples of its use for
      archaeometrical purposes are given to highlight the potential of the technique.
      Chemical information can be obtained by luminescent characterization of minerals.
      IL spectra act as digital imprint for elements or defects inside each material,
      enabling differentiation of natural specimens from imitations and/or synthetic
      analogues. Crystal field theory indicates it is the coordination number of the
      emitter inside the crystalline structure that gives information on its valence.
      Historical confusion between rubies and red spinel can easily be resolved by
      analysis of IL spectra. Modern synthetic diamonds can also be discriminated and
      blue sapphire can be distinguished from blue kyanite, a silicate that is
      currently being sold as its imitation. The technique can also differentiate
      between the synthetic and the natural gems. Polymorphs can be identified, and it
      is possible to recognize minerals from isomorphic series (from the same chemical
      group with the same structure) even when they share the same light emitter (e.g.
      Mn(2+), in carbonates). High-quality glasses (e.g. laser glasses) which are
      normally used for faking gemstones can be also detected. We fully believe IL
      will, in the future, be a powerful technique for determining the crystallinity of
      solids. This paper gives an overview of possible applications of IL to
      archaeometry for mineral characterization; this is a new application that still
      requires further study.

PMID- 17180339
TI  - Fate and occurrence of X-ray contrast media in the environment.
AB  - Interest in the presence of pharmaceuticals in the environment has recently
      increased. Despite continuous research efforts there is still a large gap in our
      knowledge of their fate and effects on the ecosystem. This review covers current
      information on the occurrence of iodinated X-ray contrast media (ICM) in the
      environment and developments in the analysis of these highly polar organic
      micropollutants in aqueous environmental samples. Findings from monitoring
      surveys conducted on wastewater-treatment plants (WWTP), surface waters, and
      drinking waters are compiled, and strategies for removal of the compounds in WWTP
      and waterworks using advanced treatment are reported. Characteristics and
      advantages of different compound-specific or element-specific mass spectrometric
      techniques used to monitor ICM in the environment are compared, and applications
      in elucidation of the structures of biotransformation products, generated in
      laboratory-scale experiments that simulate sewage treatment or river
      water/sediment systems, are described.

PMID- 17180341
TI  - Spectrally resolved fluorescence lifetime imaging microscopy (SFLIM)--an
      appropriate method for imaging single molecules in living cells.

PMID- 17180342
TI  - Mycotoxin analysis: state-of-the-art and future trends.

PMID- 17180343
TI  - Angiotensinogen impairs angiogenesis in the chick chorioallantoic membrane.
AB  - Angiotensinogen shares with other members of the serine protease inhibitor
      (serpin) family antiangiogenic properties. Angiotensinogen inhibits in vitro
      endothelial cell proliferation, and is antiangiogenic in ovo in the chick
      chorioallantoic membrane assay. The cellular mode of action of angiotensinogen
      has been studied by applying purified human angiotensinogen or Chinese hamster
      ovary cells producing recombinant angiotensinogen onto the developing
      chorioallantoic membrane. Vessel density of the control and angiotensinogen
      treated areas was quantitated by using Sambucus nigra lectin, a specific
      endothelial cell marker. After 48 h of angiotensinogen treatment by either
      applying purified angiotensinogen or angiotensinogen-producing Chinese hamster
      ovary cells, there was a 70% decrease in mesodermic vessel density in comparison
      to the control sections. Angiotensinogen treatment induced a strong decrease in
      endothelial cell proliferation of the chorioallantoic membrane vasculature, as
      shown by incorporation of bromo-deoxyuridine. Two days after local
      angiotensinogen treatment, increased apoptosis of endothelial cells of mesodermal
      blood vessels was detected by transferase-mediated deoxyuridine triphosphate nick
      end labeling assay. As assessed by in situ hybridization, the gene expression
      pattern of the main vascular growth factors and their receptors was not altered
      by angiotensinogen. Angiotensinogen, therefore, impairs angiogenesis without
      altering the expression level of vascular growth factors through the induction of
      apoptosis and decreased endothelial cell proliferation.

PMID- 17180344
TI  - Elevated placental expression of the imprinted PHLDA2 gene is associated with low
      birth weight.
AB  - The identification of genes that regulate fetal growth will help establish the
      reasons for intrauterine growth restriction. Most autosomal genes are expressed
      biallelically, but some are imprinted, expressed only from one parental allele.
      Imprinted genes are associated with fetal growth and development. The growth of
      the fetus in utero relies on effective nutrient transfer from the mother to the
      fetus via the placenta. Some current research on the genetic control of fetal
      growth has focused on genes that display imprinted expression in utero. The
      expression levels of four imprinted genes, the paternally expressed insulin
      growth factor 2 (IGF2), the mesoderm-specific transcript isoform 1 (MEST); the
      maternally expressed pleckstrin homology-like domain, family A, member 2
      (PHLDA2); and the polymorphically imprinted insulin-like growth factor 2 (IGF2R)
      gene are all known to have roles in fetal growth and were studied in the
      placentae of 200 white European, normal term babies. The quantitative expression
      analysis with real-time PCR showed the maternally expressing PHLDA2 but not the
      paternally expressing IGF2 and MEST, nor the polymorphic maternally expressing
      IGF2R placental levels to have a statistically significant effect on birth
      weight. PHLDA2 expression levels are negatively correlated with size at birth.
      These data implicate PHLDA2 as an imprinted gene important in fetal growth and
      also as a potential marker of fetal growth.

PMID- 17180345
TI  - Suicidal erythrocyte death in sepsis.
AB  - Sequelae of sepsis include anemia which presumably results from accelerated
      clearance of erythrocytes from circulating blood. The underlying mechanisms,
      however, remained hitherto elusive. Most recent studies disclosed that increased
      cytosolic Ca2+ activity and ceramide both trigger suicidal erythrocyte death
      (i.e., eryptosis), which is characterized by lipid scrambling of the cell
      membrane leading to phosphatidylserine exposure at the erythrocyte surface.
      Phosphatidylserine exposing erythrocytes may adhere to vascular walls or may be
      engulfed by macrophages equipped with phosphatidylserine receptors. To explore
      whether sepsis leads to eryptosis, erythrocytes from healthy volunteers were
      exposed to plasma of patients suffering from sepsis, or to supernatants from
      sepsis producing pathogens. Then, phosphatidylserine exposure (annexin V
      binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3
      fluorescence), and ceramide formation (anti-ceramide antibody) were determined by
      flow cytometry. Challenge of erythrocytes with plasma from the patients but not
      with plasma from healthy individuals triggered annexin V binding. The effect of
      patient plasma on erythrocyte annexin V binding was paralleled by formation of
      ceramide and a significant increase of cytosolic Ca2+ activity. Exposure of
      erythrocytes to supernatant of pathogens similarly induced eryptosis, an effect
      correlating with sphingomyelinase activity. The present observations disclose a
      novel pathophysiological mechanism leading to anemia and derangement of
      microcirculation during sepsis. Exposure to plasma from septic patients triggers
      phosphatidylserine exposure leading to adherence to the vascular wall and
      clearance from circulating blood.

PMID- 17180346
TI  - Prevalence of fecal carriage of ESBL-producing Enterobacteriaceae in hospitalized
      and ambulatory patients during two non-outbreak periods.

PMID- 17180347
TI  - Use of the INNO LiPA Rif.TB for detection of Mycobacterium tuberculosis DNA
      directly in clinical specimens and for simultaneous determination of rifampin
      susceptibility.
AB  - The INNO LiPA Rif.TB (Innogenetics, Ghent, Belgium) is a reverse hybridization
      test developed to detect genetic markers of resistance to rifampin in
      Mycobacterium tuberculosis complex. In the present study, this test was used
      directly on 3,763 clinical specimens by adopting a nested amplification of the
      target. The specificity of the system (98.4%) was optimal, but sensitivity
      (69.5%) was unsatisfactory. However, when use of the system was limited to smear
      positive specimens, the sensitivity rose to 91.7%. As expected, the ability of
      the system to predict rifampin resistance was not influenced by its direct use on
      clinical specimens and confirmed the favorable results repeatedly reported in the
      literature.

PMID- 17180348
TI  - C6 peptide ELISA test in the serodiagnosis of Lyme borreliosis in Sweden.
AB  - The aim of this study was to evaluate the synthetic C6 peptide test as a first
      line test in a two-tiered scheme for Borrelia serology in a clinically well
      characterized population of patients with Lyme borreliosis in Kalmar County,
      Sweden. The study population consisted of a prospective group (n = 200), a
      control group (n = 255), and a retrospective group (n = 29). The test panel
      consisted of the Immunetics Quick ELISA C6 Borrelia assay kit (Immunetics,
      Cambridge, MA, USA), the Virotech Borrelia burgdorferi ELISA (Genzyme Virotech,
      Russelsheim, Germany), and the Liaison Borrelia CLIA (DiaSorin, Saluggia,
      Vercelli, Italy). Seroprevalence among 200 healthy blood donors was significantly
      lower in the C6 test (8%) compared to the Virotech ELISA (14%) and the Liaison
      CLIA (12%). In convalescent sera (2-3 months and 6 months post infection) from
      158 patients with erythema migrans, the seropositivity in the C6 test was also
      significantly lower compared to both the Virotech ELISA and the Liaison CLIA.
      Serosensitivity in the acute phase of erythema migrans and other clinical
      manifestations of borreliosis did not differ significantly between the C6 test
      and the Virotech ELISA or the Liaison CLIA. Overall, a positive C6 test seems to
      correlate well with acute borreliosis. Cross-reactivity was lower in the C6 test
      in sera positive for Epstein-Barr virus infection as compared to the Virotech
      ELISA. This study supports the use of the C6 test as a screening test for
      borreliosis, in endemic areas.

PMID- 17180349
TI  - Burkholderia cepacia complex nasal isolation in immunocompetent patients with
      sinonasal polyposis not associated with cystic fibrosis.

PMID- 17180350
TI  - Changes in gene expression in beta cells after islet isolation and
      transplantation using laser-capture microdissection.
AB  - AIMS/HYPOTHESIS: The process of islet isolation can cause chemical and mechanical
      injury to beta cells. In addition, hyperglycaemia after islet transplantation can
      compromise beta cell function. The aim of this experiment was to evaluate changes
      in gene expression in endogenous islets using laser-capture microdissection
      (LCM). MATERIALS AND METHODS: Islets from B6AF1 mice were studied in situ in the
      pancreas as well as those freshly isolated or cultured for 24 h. Fresh islets
      were transplanted under the kidney capsule of syngeneic diabetic (streptozocin
      induced) and non-diabetic mice. Frozen sections from all the samples were
      prepared for LCM to obtain beta cell-enriched tissue; RNA was extracted and
      amplified using T7 polymerase. RT-PCR was used to assess expression of selected
      genes critical for beta cell function (Ins, Ipf1 [previously known as Pdx1],
      Slc2a2 [previously known as GLUT2] and Ldha) and the stress response (Hmox1
      [previously known as HO-1], Gpx1, Tnfaip3 [previously known as A20] and Fas).
      Immunostaining was also performed. RESULTS: In freshly isolated and cultured
      islets, insulin and Ipf1 mRNA levels were decreased by 40% (compared with islets
      in situ), while stress genes were upregulated. Comparison between in situ
      pancreatic islets and engrafted beta cells of cured mice showed declines in Ipf1
      expression. CONCLUSIONS/INTERPRETATION: Our experiment, the first report to
      investigate changes in gene expression in endogenous islets using LCM, indicate
      that beta cells following islet isolation and residing in a foreign graft
      environment have decreased expression of genes involved in insulin production and
      increased expression of stress genes. Our data suggest that an islet graft, even
      in successful transplantation, may be different from endogenous islets in gene
      expression.

PMID- 17180351
TI  - Impaired insulin secretion in vivo but enhanced insulin secretion from isolated
      islets in pancreatic beta cell-specific vascular endothelial growth factor-A
      knock-out mice.
AB  - AIMS/HYPOTHESIS: Endothelial cells are considered to be essential for normal
      pancreatic beta cell function. However, there have been no reports showing their
      importance for beta cell function. MATERIALS AND METHODS: Using mice with
      disrupted vascular endothelial growth factor-A gene specifically in beta cells,
      we investigated the relation between islet vascular structure and beta cell
      function. RESULTS: Mice with disrupted vascular endothelial growth factor-A gene
      specifically in beta cells had reduced islet vascular density with impaired
      formation of endothelial fenestration. While their fasting glucose and body
      weight were comparable with control mice, their glucose- and tolbutamide-induced
      rapid insulin release were impaired, thus resulting in glucose intolerance. On
      the other hand, glucose and KCl enhanced the levels of insulin secreted from
      islets isolated from these mice. In addition, the production of soluble N
      ethylmaleimide-sensitive factor attachment protein receptors in the islets was
      increased. Insulin content and expression of insulin I and pancreas duodenum
      homeobox 1 mRNA in the islets were also increased. CONCLUSIONS/INTERPRETATION:
      Our results indicate that an abnormal quality and quantity of blood vessels due
      to reduced expression of vascular endothelial growth factor-A in beta cells could
      be a cause of impaired insulin secretion without impairment of beta cell
      function.

PMID- 17180352
TI  - Role of inflammatory mediators in the suppression of insulin receptor
      phosphorylation in circulating mononuclear cells of obese subjects.
AB  - AIMS/HYPOTHESIS: Obesity is associated with insulin resistance and inflammation.
      The circulating human mononuclear cell (MNC) has been shown to respond to low
      dose insulin infusion. We have now investigated whether in obesity: (1)
      phosphorylated insulin receptor beta subunit (p-INSR-beta) is reduced in the MNC;
      (2) pro-inflammatory mediators including inhibitor of kappa light polypeptide
      gene enhancer in B cells-kinase beta (IKBKB), suppressor of cytokine signalling-3
      (SOCS) and protein kinase C-beta 2 (PRKCB2) are increased and related to p-INSR
      beta; and (3) the reduction in MNC p-INSR-beta is related to the reduction in
      insulin sensitivity. MATERIALS AND METHODS: MNCs were prepared from fasting blood
      samples of 16 normal weight and 16 obese female subjects. RESULTS: Our data show
      that p-INSR-beta is reduced significantly in MNCs from obese subjects compared
      with that of normal controls. MNCs from obese subjects have higher IKBKB
      expression, increased nuclear factor kappa B (NFkappaB) binding and higher mRNA
      expression of TNFAIP1 and IL6 genes. NFkappaB binding, TNFAIP1 mRNA and plasma C
      reactive protein are inversely related to p-INSR-beta. PRKCB2 mRNA and protein
      expression were significantly higher in the obese subjects and were related
      significantly to pro-inflammatory mediators but not to p-INSR-beta. SOCS3 mRNA
      expression was markedly elevated and positively related to pro-inflammatory
      mediators including IKBKB and PRKCB2 on the one hand and inversely related to p
      INSR-beta on the other. CONCLUSIONS/INTERPRETATION: We conclude that in obesity
      the MNC is characterised by reduced p-INSR-beta and increased inflammatory
      mediators including IKBKB, PRKCB2 and SOCS3. The increase in SOCS3 but not IKBKB
      or PRKCB2 is related inversely to p-INSR-beta and might mediate the inhibition of
      p-INSR-beta. These data elucidate the relationship between inflammation and
      insulin resistance using the MNC as a model.

PMID- 17180353
TI  - Epidemiological characteristics of diabetes mellitus and impaired glucose
      regulation in a Chinese adult population: the Shanghai Diabetes Studies, a cross
      sectional 3-year follow-up study in Shanghai urban communities.
AB  - AIMS/HYPOTHESIS: To estimate the prevalence and incidence of diabetes mellitus
      and impaired glucose regulation (IGR) in a Chinese population aged 20-94 years.
      SUBJECTS AND METHODS: A group of 5,628 randomly selected adults, aged 20-94
      years, living in the Huayang and Caoyang communities in Shanghai, China, were
      investigated between 1998 and 2001. During 2002-04, 2,666 subjects were followed
      up. All the participants underwent anthropometric measurements, blood biochemical
      analyses and a 75-g OGTT. RESULTS: Based on the 2000 census data of China, the
      age-standardised prevalences were 6.87% for diabetes and 8.53% for IGR at
      baseline. More than two in five cases with diabetes were undiagnosed. The age
      adjusted prevalence of diabetes and IGR increased with age. The age-adjusted
      prevalences of hypertension, dyslipidaemia and overweight in males were
      significantly higher (p < 0.001) than in females. The 3-year cumulative incidence
      rates of diabetes and IGR were 4.96 and 11.10%, respectively. The relative risk
      of developing diabetes was significantly higher in subjects with IGR than in
      subjects with NGT (p < 0.001). CONCLUSIONS/INTERPRETATION: The prevalence and
      incidence rates for diabetes or IGR have increased dramatically over the last
      decades, especially in younger age groups. A large proportion of cases are
      undiagnosed. We strongly recommend that population-based diabetes screening
      programmes should be implemented and generalised for younger people.

PMID- 17180354
TI  - Increased expression of CCAAT/enhancer binding protein-beta and -delta and
      monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats.
AB  - AIMS/HYPOTHESIS: We evaluated whether hyperinsulinaemia stimulates the expression
      of transcription factor CCAAT/enhancer binding protein (C/EBP)-beta and C/EBP
      delta and leads to the induction of the chemokine (C-C motif) ligand 2 gene
      (Ccl2, also known as MCP-1) expression in aortas. METHODS: Hyperinsulinaemia was
      induced by feeding rats a high-fructose diet. CCL2 production was analysed by
      ELISA. The expression of Ccl2, Cebpb and Cebpd mRNAs was investigated by
      quantitative RT-PCR. The binding of C/EBP-beta to Ccl2 was assessed by chromatin
      immunoprecipitation (ChIP) assay. RESULTS: Insulin at a concentration of 10
      nmol/l significantly stimulated the expression of Cebpb, Cebpd and Ccl2 mRNAs,
      depending on activation of phosphatidylinositol 3-kinase (PI3K) in cultured
      vascular smooth muscle cells. The knock-down of C/EBP-beta with siRNA abolished
      the insulin-induced Ccl2 mRNA expression. In the aortas from fructose-fed rats,
      the levels of phosphorylation of Akt/protein kinase B, a downstream effector of
      PI3K, were also increased. The expression of Cebpb, Cebpd and Ccl2 mRNAs in the
      aortas from fructose-fed rats were significantly elevated, by 330, 300 and 300%,
      respectively, compared with those of control-fed rats. The induction Ccl2 mRNA
      expression in the aortas was significantly correlated with the expression of
      Cebpb and Cebpd mRNAs in the aortas. Furthermore, the ChIP assay showed elevated
      binding of C/EBP-beta to the 5' upstream region of Ccl2 in the aortas from
      fructose-fed rats. CONCLUSIONS/INTERPRETATION: These findings clearly indicate
      the role of C/EBPs in the mechanism of upregulation of CCL2, an inflammation
      related protein, observed in the hyperinsulinaemic state, which may initiate the
      process of atherosclerosis.

PMID- 17180355
TI  - [Modern diagnosis of Chlamydia trachomatis infections].
AB  - Chlamydia trachomatis is the most frequent sexually transmitted bacterial
      infection. Tests to diagnose C. trachomatis infections include growth on cell
      culture and assays detecting bacterial antigens or nucleic acids. Until recently,
      culture was considered the gold standard of testing because of its high
      specificity. However, the sensitivity of culture is limited. Nucleic acid
      amplification tests (NATs) have the highest sensitivity and are almost as
      specific as culture. They are best suited for screening. Chlamydial antigen EIAs
      are considerably less sensitive and specific, resulting in low positive
      predictive values, especially when low-prevalence populations are studied. Thus,
      positive results of chlamydia antigen EIAs should be confirmed by another test.

PMID- 17180356
TI  - Cervical disc prosthesis replacement and interbody fusion: a comparative study.
AB  - The purpose of this paper is to compare the new functional intervertebral
      cervical disc prosthesis replacement and the classical interbody fusion
      operation, including the clinical effect and maintenance of the stability and
      segmental motion of cervical vertebrae. Twenty-four patients with single C5-6
      intervertebral disk hernias were specifically selected and divided randomly into
      two groups: One group underwent artificial cervical disc replacement and the
      other group received interbody fusion. All patients were followed up and
      evaluated. The operation time for the single disc replacement was (130 +/- 50)
      minutes and interbody fusion was (105 +/- 53) minutes. Neurological or vascular
      complications were not observed during or after operation. There was no
      prosthesis subsidence or extrusion. The JOA score of the group with prosthesis
      replacement increased from an average of 8.6 to 15.8. The JOA score of the group
      with interbody fusion increased from an average of 9 to 16.2. The clinical effect
      and the ROM of the adjacent space of the two groups showed no statistical
      difference. The short follow-up time does not support the advantage of the
      cervical disc prosthesis. The clinical effect and the maintenance of the function
      of the motion of the intervertebral space are no better than the interbody
      fusion. At least 5 years of follow-up is needed to assess the long-term
      functionality of the prosthesis and the influence on adjacent levels.

PMID- 17180357
TI  - Patterns of peroxidative ethane emission from submerged rice seedlings indicate
      that damage from reactive oxygen species takes place during submergence and is
      not necessarily a post-anoxic phenomenon.
AB  - Using ethane as a marker for peroxidative damage to membranes by reactive oxygen
      species (ROS) we examined the injury of rice seedlings during submergence in the
      dark. It is often expressed that membrane injury from ROS is a post-submergence
      phenomenon occurring when oxygen is re-introduced after submergence-induced
      anoxia. We found that ethane production, from rice seedlings submerged for 24-72
      h, was stimulated to 4-37 nl gFW(-1), indicating underwater membrane
      peroxidation. When examined a week later the seedlings were damaged or had died.
      On de-submergence in air, ethane production rates rose sharply, but fell back to
      less than 0.1 nl gFW(-1) h(-1) after 2 h. We compared submergence-susceptible and
      submergence-tolerant cultivars, submergence starting in the morning (more damage)
      and in the afternoon (less damage) and investigated different submergence
      durations. The seedlings showed extensive fatality whenever total ethane emission
      exceeded about 15 nl gFW(-1). Smaller amounts of ethane emission were linked to
      less extensive injury to leaves. Partial oxygen shortage (O(2) levels <1%)
      imposed for 2 h in gas phase mixtures also stimulated ethane production. In
      contrast, seedlings under anaerobic gas phase conditions produced no ethane until
      re-aerated: then a small peak was observed followed by a low, steady ethane
      production. We conclude that damage during submergence is not associated with
      extensive anoxia. Instead, injury is linked to membrane peroxidation in seedlings
      that are partially oxygen deficient while submerged. On return to air, further
      peroxidation is suppressed within about 2 h indicating effective control of ROS
      production not evident during submergence itself.

PMID- 17180358
TI  - Indolacetic and humic acids induce lateral root development through a concerted
      plasmalemma and tonoplast H+ pumps activation.
AB  - Increasing evidences have indicated that humic substances can induce plant growth
      and productivity by functioning as an environmental source of auxinic activity.
      Here we comparatively evaluate the effects of indole-3-acetic acid (IAA) and
      humic acids (HA) isolated from two different soils (Inseptsol and Ultisol) and
      two different organic residues (vermicompost and sewage sludge) on root
      development and on activities of plasmalemma and tonoplast H(+ )pumps from maize
      roots. The data show that HA isolated from these different sources as well as low
      IAA concentrations (10(-10) and 10(-15) M) improve root growth through a markedly
      proliferation of lateral roots along with a differential activation not only of
      the plasmalemma but also of vacuolar H(+)-ATPases and H(+)-pyrophosphatase.
      Further, the vacuolar H(+)-ATPase had a peak of stimulation in a range from 10(
      8) to 10(-10) M IAA, whereas the H(+)-pyrophosphatase was sensitive to a much
      broader range of IAA concentrations from 10(-3) to 10(-15) M. It is proposed a
      complementary view of the acid growth mechanism in which a concerted activation
      of the plasmalemma and tonoplast H(+ )pumps plays a key role in the root cell
      expansion process driven by environment-derived molecules endowed with auxinic
      activity, such as that of humic substances.

PMID- 17180359
TI  - The family of DOF transcription factors: from green unicellular algae to vascular
      plants.
AB  - This article deals with the origin and evolution of the DOF transcription factor
      family through a phylogenetic analysis of those DOF sequences identified from a
      variety of representative organisms from different taxonomic groups: the green
      unicellular alga Chlamydomonas reinhardtii, the moss Physcomitrella patens, the
      fern Selaginella moellendorffii, the gymnosperm Pinus taeda, the dicotyledoneous
      Arabidopsis thaliana and the monocotyledoneous angiosperms Oryza sativa and
      Hordeum vulgare. In barley, we have identified 26 different DOF genes by sequence
      analyses of clones isolated from the screening of genomic libraries and of ESTs,
      whereas a single DOF gene was identified by bioinformatics searches in the
      Chlamydomonas genome. The phylogenetic analysis groups all these genes into six
      major clusters of orthologs originated from a primary basal grade. Our results
      suggest that duplications of an ancestral DOF, probably formed in the
      photosynthetic eukaryotic ancestor, followed by subsequent neo-, sub
      functionalization and pseudogenization processes would have triggered the
      expansion of the DOF family. Loss, acquisition and shuffling of conserved motifs
      among the new DOFs likely underlie the mechanism of formation of the distinct
      subfamilies.

PMID- 17180360
TI  - Gadolinium and nephrogenic fibrosing dermopathy in pediatric patients.

PMID- 17180361
TI  - Clinical predictors of neurocognitive deficits in children with chronic kidney
      disease.
AB  - The purpose of the study was to explore associations between neurocognitive
      function and chronic kidney disease (CKD)-related clinical characteristics.
      Twenty-nine children, ages 7 to 19 years, with an estimated creatinine clearance
      (eCrCl) of 4-89 ml/min per 1.73 m2 body surface area were enrolled. Intellectual
      function (IQ), memory, and attention were measured and expressed as age-based
      standard scores. Clinical data were obtained by physical examination, laboratory
      testing, parental questionnaires and medical chart review. Pearson correlations
      and standard Student's t-tests were used to identify significant (P < 0.05)
      relationships between targeted clinical variables and neurocognitive scores.
      Increased CKD severity correlated with lower IQ (P = 0.001) and memory function
      (P = 0.02). Memory function was lower in children with longer duration of disease
      (P = 0.03). Similarly, IQ scores were lowest when kidney disease had started at a
      younger age (P = 0.03) and with a greater percent of life with CKD (P = 0.04).
      Our findings provide preliminary evidence that increased disease severity, longer
      duration of disease, and younger age of onset of kidney disease potentially place
      children with CKD at increased risk of neurocognitive deficits. Additional
      investigation is required to better quantify these risk factors, particularly
      regarding how much variability is accounted for by these specific risk factors.

PMID- 17180362
TI  - Comparison of chronic peritoneal dialysis outcomes in children with and without
      spina bifida.
AB  - This study was designed to compare chronic peritoneal dialysis (CPD) long-term
      outcomes (patient and technique survival, incidence of peritonitis, and overall
      average death outcomes) between seven patients with lumbar spina bifida (SB) and
      20 controls without SB. Both groups were matched for potentially outcome
      confounding factors: gender, and socioeconomic status (SES). SES was established
      using modified Graffar's method. No significant differences were found in CPD
      outcomes. The incidence of peritonitis was one episode per 17.6 and 10.3 months
      in SB patients and controls, respectively (p = 0.5). Overall patient survival at
      5 years was 86% and 73% in SB patients and controls, respectively (p = 0.55).
      Overall average death rate between SB and control patients was 47.6/1,000 and
      79.4/1,000 patient years, respectively (p = 0.63). Overall technique survival at
      5 years was 83% and 73% in SB patients and controls, respectively (p = 0.84).
      There were no cases of retrograde brain ventricular infection secondary to PD
      related peritonitis. We conclude that SB is not a risk factor for CPD, and
      therefore, it is an effective renal replacement alternative in children with SB.

PMID- 17180363
TI  - Is typing for HLA class II alleles beneficial in Indian children with idiopathic
      nephrotic syndrome?
AB  - This study was conducted to test the hypothesis that analysis of HLA class II
      type alleles will give important information on the prognosis of NS in children.
      We prospectively studied 100 consecutive children with idiopathic nephrotic
      syndrome and 202 controls belonging to the same geoethnic background. Typing for
      HLA Class II alleles at DR and DQ locus was carried out by using SSP (sequence
      specific oligonucleotides based method). In our study children were more likely
      to have nephrotic syndrome if the allele DQ-beta1*020X was present as compared to
      controls. On the other hand, DR-beta1*1001, DR-beta1*130X and DQ-beta1*030X were
      significantly lower among patients and likely to be protective. On analysing the
      different steroid response categories, we observed that the allele DQ-beta1*020X
      was significantly higher in infrequent relapsers (IFR) with a high etiological
      fraction of 0.714. Children were more likely to be steroid resistant if the
      allele DR-beta1*150X was present and the etiological fraction was high (0.754).
      The allele DQ-beta1*030X was significantly lower in steroid resistant patients
      (p=0.019, RR=0.1819, 95% CI=0.04430-0.7471) and likely to be protective. On
      analysing the haplotype distribution, we observed that occurrence of DR
      beta1*070X-DQ-beta1*020X haplotype was significantly more common among patients
      with steroid sensitive nephrotic syndrome (23.94%) as compared to controls
      (12.5%) (p=0.01). In the steroid resistant group we observed that the haplotype
      DR-beta1*150X-DQ-beta1*060X was significantly more frequent as compared to
      steroid sensitive patients as well as controls p=0.01. We conclude that HLA
      typing in Indian children with NS helps to predict relapse frequency and steroid
      resistance.

PMID- 17180364
TI  - Gender difference in achieving rate of maturity of the vesicoureteric junction.
AB  - BACKGROUND: Our previous study on the Doppler waveform of the urinary jet at the
      vesicoureteric junction (VUJ) indicates that there is an active sphincteric
      mechanism in humans. We have also shown that there are immature and mature
      patterns of the jet, and the VUJ matures around the age of 4 years. OBJECTIVE: To
      determine if there is any gender difference in the time of achieving maturity of
      the VUJ. MATERIALS AND METHODS: The Doppler pattern of the jets from both ureters
      was recorded in 273 normal boys and 248 normal girls. The subjects were
      considered to have immaturity of the VUJ if an immature jet waveform was detected
      in either ureter. RESULTS: The mean age of VUJ maturity was 4.54 years for the
      whole population, 4.88 years for boys and 4.34 years for girls. The difference
      between ROC curves for boys and girls was not significant (P > 0.05, simple Z
      test). CONCLUSION: There is no significant gender difference in the maturation of
      the VUJ. Detection of a persistent immature jet pattern beyond the age of
      maturity might have prognostic implications if there is a concurrent pathological
      condition related to the urinary tract in children.

PMID- 17180365
TI  - Muscle changes in brachial plexus birth injury with elbow flexion contracture: an
      MRI study.
AB  - BACKGROUND: Muscle pathology of the arm and forearm in brachial plexus birth
      injury (BPBI) with elbow flexion contracture has not been evaluated with MRI.
      OBJECTIVE: To determine whether limited range of motion of the elbow in BPBI is
      correlated with specific patterns of muscular pathology. MATERIALS AND METHODS:
      For 15 BPBI patients, total active motion (TAM) of the elbow (extension-flexion)
      and the forearm (pronation-supination) were measured. MRI of the elbow joints and
      musculature allowed assessment of elbow congruency. Fatty infiltration and size
      reduction of the muscles were graded semiquantitatively. RESULTS: Mean TAM of the
      elbow was 113 degrees (50 degrees-140 degrees) and that of the forearm 91 degrees
      (10 degrees-165 degrees). The greater the size reduction of the brachioradialis
      muscle, the more diminished was elbow TAM. The more extensive the BPBI and muscle
      pathology of the pronator teres muscle, the more limited was the TAM of the
      forearm. Pathology of the supinator and brachialis muscles was evident in every
      patient. CONCLUSION: Extensive BPBI may result in marked limitation of TAM. Elbow
      flexion contracture seems to be caused mainly by brachialis muscle pathology.
      Prosupination of the forearm is better preserved when the pronator teres is not
      severely affected. MRI can reliably show the extent of muscle pathology in BPBI.

PMID- 17180366
TI  - Pelvic MRI in children with Crohn disease and suspected perianal involvement.
AB  - MRI is an important imaging tool in evaluation of adult and pediatric patients
      with Crohn disease. Pelvic MRI, in particular, has become the method of choice to
      evaluate for perianal fistulas and associated complications of Crohn disease. MRI
      can define the extent and location of perianal fistulas and abscesses, as well as
      provide critical information for operative management. In this pictorial essay,
      we describe useful MRI techniques for evaluation of perianal complications in
      pediatric patients with Crohn disease. We review pertinent anatomy and illustrate
      typical examples of perianal fistulas with and without abscess. We show one case
      of clinically suspected perianal fistula that was actually a pilonidal sinus.

PMID- 17180367
TI  - CT features of tuberculous intracranial abscesses in children.
AB  - BACKGROUND: Intracranial tuberculous (TB) abscesses still cause a diagnostic
      dilemma on both CT and MRI as they may mimic neoplasms. Recognition of TB
      abscesses may prompt further imaging and appropriate trial of therapy, and may
      reduce the need for biopsy. OBJECTIVE: To report the CT features of eight
      intracranial TB lesions in children initially diagnosed as neoplasms and
      eventually treated as TB abscesses. MATERIALS AND METHODS: We undertook a 3-year
      retrospective review of children with an initial CT diagnosis of intracranial
      neoplasm who were subsequently diagnosed as having TB abscesses. RESULTS: Eight
      patients out of 60 with an initial diagnosis of a neoplasm on CT were
      misdiagnosed and were ultimately determined to have TB abscesses after biopsy or
      a trial of anti-TB therapy. The most consistent constellation of findings for the
      lesions were low density (n = 5), ring enhancement (n = 8), cerebral hemisphere
      location (n = 7), mass effect (n = 6), surrounding oedema (n = 5) and absence of
      a soft-tissue-density mass (n = 8). CONCLUSION: In endemic regions, intracranial
      lesions with these appearances on CT should undergo further imaging and possibly
      a trial of anti-TB therapy before considering biopsy.

PMID- 17180368
TI  - Retrograde flow in the dural sinuses detected by three-dimensional time-of-flight
      MR angiography.
AB  - INTRODUCTION: Retrograde flow in the left dural sinuses is sometimes detected by
      three-dimensional time-of-flight (3D-TOF) magnetic resonance (MR) angiography.
      The purpose of this study was to evaluate the incidence of this phenomenon and
      its characteristic features on 3D-TOF MR angiograms. METHODS: We retrospectively
      reviewed cranial MR angiography images of 1,078 patients examined at our
      institution. All images were obtained by the 3D-TOF technique with one of two 1.5
      T scanners. Maximum intensity projection (MIP) images in the horizontal rotation
      view were displayed stereoscopically. We reviewed the source images,
      inferosuperior MIP images, and horizontal MIP images and identified retrograde
      flow in the dural sinuses. RESULTS: We found retrograde flow in the dural sinuses
      of 67 patients on the source images from 3D-TOF MR angiography; the incidence was
      6.2%. In 47 of the 67 patients, retrograde flow was identified in the left
      inferior petrosal sinus, in 13, it was seen in the left sigmoid sinus, and in 6,
      it was seen in the left inferior petrosal and left sigmoid sinuses. The remaining
      patient had retrograde flow in the left inferior petrosal and left and right
      sigmoid sinuses. The mean age of the patients with retrograde flow was slightly
      greater than that of the patients without this phenomenon (70 years vs 63 years).
      CONCLUSION: Retrograde flow in the dural sinuses frequently occurs on the left
      side in middle-aged and elderly patients during 3D-TOF MR angiography performed
      with the patient in the supine position. This phenomenon should not be
      misdiagnosed as a dural arteriovenous fistula.

PMID- 17180369
TI  - Drought effects on above- and belowground production of a grazed temperate
      grassland ecosystem.
AB  - The effect of climatic variation on terrestrial aboveground productivity (ANPP)
      has been well studied. However, little is known about how variable climate,
      including drought, may influence belowground productivity (BNPP), which
      constitutes most of the annual primary production of grasslands. The objectives
      of this study were to (1) examine how a 3-year period of declining moisture,
      which began as climatically wet to average across Yellowstone National Park (YNP)
      and ended in drought, affected ANPP and BNPP in grasslands of YNP and (2) how
      herds of grazing ungulates, which were shown previously to stimulate grassland
      shoot and root growth in YNP, may have interacted with climatic conditions to
      influence grassland production. ANPP and 0-20 cm BNPP, representing the bulk of
      the root dynamics, were measured in grazed and ungrazed (fenced) grassland at
      nine sites ranging widely in elevation, soil conditions and plant production
      during the 3-year study. Results revealed that 0-20 cm BNPP was strongly
      influenced by drought (P = 0.0005) and declined from 1999 to 2001 among ungrazed
      and grazed grasslands by 39 and 49%, respectively. The greater reduction in 0-20
      cm BNPP among grazed grasslands was due, in part, to a decline (P = 0.07) in the
      stimulatory effect of grazing, i.e., the ratio g BNPP stimulated: g shoot
      consumed. In contrast, ANPP was unaffected by drought in either type of
      grassland. Thus, the effect of this drought in YNP was a large reduction in BNPP,
      which was a function of (1) a direct negative influence of increased moisture
      stress on root growth and (2) a weak interaction between drought and herbivory
      that led to a decline in the positive feedback from grazers to BNPP. These
      findings highlight the need to better understand factors that control root growth
      and to study the effects of climatic variation on grasslands within an ecosystem
      framework to include potentially important climate-consumer interactions.

PMID- 17180370
TI  - Fitness consequences of infection of Arabidopsis thaliana with its natural
      bacterial pathogen Pseudomonas viridiflava.
AB  - Variation in plant resistance to pathogen infection is commonly observed in
      interactions between wild plants and their foliar pathogens. Models of host
      pathogen interactions indicate that a large cost of infection is generally
      necessary to maintain this variation, yet there is limited evidence that foliar
      pathogens cause detectable fitness reductions in wild host plants. Most published
      work has focused on fungal pathogens. Pseudomonas viridiflava, a common bacterial
      pathogen of the annual weed Arabidopsis thaliana across its range, comprises two
      distinct genetic clades that cause disease symptoms of different severity. Here
      we measured the extent of infection of wild A. thaliana populations in the
      Midwest, USA, and examined the effect on seed production, in field and growth
      chamber experiments, of experimental inoculation with isolates from the two
      clades. We found infection with P. viridiflava varied from 0 to 56% in Midwest A.
      thaliana populations, with the possibility of several leaves per plant infected
      later in the growing season. In the growth chambers, experimental inoculation
      reduced seed set by averages of 15 and 11% for clades A and B, respectively. In
      the field experiment, only clade A affected plant fitness significantly, reducing
      seed set by an average of 38%. Underlying these average effects we observed both
      negative and positive effects of infection, and variation in both fitness among
      plant genotypes and sensitivity to environmental conditions.

PMID- 17180371
TI  - The role of genetic and chemical variation of Pinus sylvestris seedlings in
      influencing slug herbivory.
AB  - This study investigated the genetic and chemical basis of resistance of Pinus
      sylvestris seedlings to herbivory by a generalist mollusc, Arion ater. Using
      feeding trials with captive animals, we examined selective herbivory by A. ater
      of young P. sylvestris seedlings of different genotypes and correlated
      preferences with seedling monoterpene levels. We also investigated the feeding
      responses of A. ater to artificial diets laced with two monoterpenes, Delta(3)
      carene and alpha-pinene. Logistic regression indicated that two factors were the
      best predictors of whether seedlings in the trial would be consumed. Individual
      slug variation (replicates) was the most significant factor in the model;
      however, alpha-pinene concentration (also representing beta-pinene, Delta(3)
      carene and total monoterpenes due to multicollinearity) of needles was also a
      significant factor. While A. ater did not select seedlings on the basis of
      family, seedlings not eaten were significantly higher in levels of alpha-pinene
      compared to seedlings that were consumed. We also demonstrated significant
      genetic variation in alpha-pinene concentration of seedlings between different
      families of P. sylvestris. Nitrogen and three morphological seedling
      characteristics (stem length, needle length and stem diameter) also showed
      significant genetic variation between P. sylvestris families. Artificial diets
      laced with high (5 mg g(-1) dry matter) quantities of either Delta(3)-carene or
      alpha-pinene, were eaten significantly less than control diets with no added
      monoterpenes, supporting the results of the seedling feeding trial. This study
      demonstrates that A. ater selectively feed on P. sylvestris seedlings and that
      this selection is based, in part, on the monoterpene concentration of seedlings.
      These results, coupled with significant genetic variation in alpha-pinene
      concentration of seedlings and evidence that slug herbivory is detrimental to P.
      sylvestris fitness, are discussed as possible evidence for A. ater as a selective
      force on the evolution of defensive chemistry in P. sylvestris.

PMID- 17180372
TI  - Beaver herbivory on aquatic plants.
AB  - Herbivores have strong impacts on marine and terrestrial plant communities, but
      their impact is less well studied in benthic freshwater systems. For example,
      North American beavers (Castor canadensis) eat both woody and non-woody plants
      and focus almost exclusively on the latter in summer months, yet their impacts on
      non-woody plants are generally attributed to ecosystem engineering rather than
      herbivory. Here, we excluded beavers from areas of two beaver wetlands for over 2
      years and demonstrated that beaver herbivory reduced aquatic plant biomass by
      60%, plant litter by 75%, and dramatically shifted plant species composition. The
      perennial forb lizard's tail (Saururus cernuus) comprised less than 5% of plant
      biomass in areas open to beaver grazing but greater than 50% of plant biomass in
      beaver exclusions. This shift was likely due to direct herbivory, as beavers
      preferentially consumed lizard's tail over other plants in a field feeding assay.
      Beaver herbivory also reduced the abundance of the invasive aquatic plant
      Myriophyllum aquaticum by nearly 90%, consistent with recent evidence that native
      generalist herbivores provide biotic resistance against exotic plant invasions.
      Beaver herbivory also had indirect effects on plant interactions in this
      community. The palatable plant lizard's tail was 3 times more frequent and 10
      times more abundant inside woolgrass (Scirpus cyperinus) tussocks than in
      spatially paired locations lacking tussocks. When the protective foliage of the
      woolgrass was removed without exclusion cages, beavers consumed nearly half of
      the lizard's tail leaves within 2 weeks. In contrast, leaf abundance increased by
      73-93% in the treatments retaining woolgrass or protected by a cage. Thus,
      woolgrass tussocks were as effective as cages at excluding beaver foraging and
      provided lizard's tail plants an associational refuge from beaver herbivory.
      These results suggest that beaver herbivory has strong direct and indirect
      impacts on populations and communities of herbaceous aquatic plants and extends
      the consequences of beaver activities beyond ecosystem engineering.

PMID- 17180373
TI  - Correlated variation of floral and leaf traits along a moisture availability
      gradient.
AB  - Variation in flower size is an important aspect of a plant's life history, yet
      few studies have shown how flower size varies with environmental conditions and
      to what extent foliar responses to the environment are correlated with flower
      size. The objectives of this study were to (1) develop a theoretical framework
      for linking flower size and leaf size to their costs and benefits, as assessed
      using foliar stable carbon isotope ratio (delta(13)C) under varying degrees of
      water limitation, and then (2) examine how variation in flower size within and
      among species growing along a naturally occurring moisture availability gradient
      correlates with variation in delta(13)C and leaf size. Five plant species were
      examined at three sites in Oregon. Intra- and inter-specific patterns of flower
      size in relation to moisture availability were the same: the ratios of the area
      of flower display to total leaf area and of individual flower area to leaf area
      were greater at sites with more soil moisture compared to those sites with less
      soil moisture. The increase in flower area per unit increase in leaf area was
      greater at sites with more soil moisture than at sites where water deficit can
      occur. Values of delta(13)C, an index of water-use efficiency, were greater for
      plants with larger floral size. The patterns we observed generalize across
      species, irrespective of overall plant morphology or pollination system. These
      correlations between flower size, moisture availability, and delta(13)C suggest
      that water loss from flowers can influence leaf responses to the environment,
      which in turn may indirectly mediate an effect on flower size.

PMID- 17180374
TI  - Importance of fragmentation-tolerant species as seed dispersers in disturbed
      landscapes.
AB  - Forest fragmentation can negatively affect plants if animal seed-dispersers
      become locally extinct in fragments. We conducted a 2-year experiment to evaluate
      the importance of tree squirrels (Sciurus) as seed dispersers for Quercus, Carya,
      and Juglans, and to assess dispersal consequences in patches where fragmentation
      sensitive eastern gray squirrels (Sciurus carolinensis) are absent. We accounted
      for fates of approximately 15,700 seeds from five tree species in four exclosure
      treatments at 18 fragments during a high (2003-2004) and low seed (2004-2005)
      year. Two treatments excluded Sciurus to mimic disperser loss. We sampled nut
      tree seedling density at 259 sites across eight watersheds, half of which were
      too fragmented to support S. carolinensis, but supported fragmentation-tolerant
      fox squirrels (Sciurus niger). Autumn-to-spring seed survival was low (
      approximately 1%) for all species during low seed production. During high seed
      production, survival was higher for Juglans nigra (20%) and Carya ovata (16%)
      than for three Quercus species ( approximately 4% for Quercus palustris and
      Quercus rubra in two exclosure types; approximately 1% for Quercus alba in all
      treatments). Survival of J. nigra, C. ovata, and Q. rubra was >or=2.1-7.7 times
      higher for seeds in exclosures that Sciurus could access. Seed displacement
      distance was higher in the low seed than the seed-rich year, but the proportion
      of seeds surviving to greater distances was higher in seed-rich years for all
      seed types except Q. rubra. This affirms the importance of masting to seed
      survival and dispersal, but also suggests an advantage to trees of producing seed
      in non-mast years. Seedling densities were comparable in watersheds with and
      without S. carolinensis. These results demonstrate the importance of tree
      squirrels as dispersers of nut-bearing trees, but suggest that fragmentation may
      not disrupt dispersal of certain species if losing S. carolinensis from disturbed
      landscapes is compensated for by fragmentation-tolerant fox squirrels (S. niger).

PMID- 17180375
TI  - A mechanism for morphogen-controlled domain growth.
AB  - Many developmental systems are organised via the action of graded distributions
      of morphogens. In the Drosophila wing disc, for example, recent experimental
      evidence has shown that graded expression of the morphogen Dpp controls cell
      proliferation and hence disc growth. Our goal is to explore a simple model for
      regulation of wing growth via the Dpp gradient: we use a system of reaction
      diffusion equations to model the dynamics of Dpp and its receptor Tkv, with
      advection arising as a result of the flow generated by cell proliferation. We
      analyse the model both numerically and analytically, showing that uniform domain
      growth across the disc produces an exponentially growing wing disc.

PMID- 17180376
TI  - Genetic mapping of sulfur assimilation genes reveals a QTL for onion bulb
      pungency.
AB  - Onion exhibits wide genetic and environmental variation in bioactive organosulfur
      compounds that impart pungency and health benefits. A PCR-based molecular marker
      map that included candidate genes for sulfur assimilation was used to identify
      genomic regions affecting pungency in the cross 'W202A' x 'Texas Grano 438'.
      Linkage mapping revealed that genes encoding plastidic ferredoxin-sulfite
      reductase (SiR) and plastidic ATP sulfurylase (ATPS) are closely linked (1-2 cM)
      on chromosome 3. Inbred F(3) families derived from the F(2 )population used to
      construct the genetic map were grown in replicated trials in two environments and
      bulb pungency was evaluated as pyruvic acid or lachrymatory factor. Broad-sense
      heritability of pungency was estimated to be 0.78-0.80. QTL analysis revealed
      significant associations of both pungency and bulb soluble solids content with
      marker intervals on chromosomes 3 and 5, which have previously been reported to
      condition pleiotropic effects on bulb carbohydrate composition. Highly
      significant associations (LOD 3.7-8.7) were observed between ATPS and SiR Loci
      and bulb pungency but not with bulb solids content. This association was
      confirmed in two larger, independently derived F(2) families from the same cross.
      Single-locus models suggested that the partially dominant locus associated with
      these candidate genes controls 30-50% of genetic variation in pungency in these
      pedigrees. These markers may provide a practical means to select for lower
      pungency without correlated selection for lowered solids.

PMID- 17180377
TI  - Genetic distance sampling: a novel sampling method for obtaining core collections
      using genetic distances with an application to cultivated lettuce.
AB  - This paper introduces a novel sampling method for obtaining core collections,
      entitled genetic distance sampling. The method incorporates information about
      distances between individual accessions into a random sampling procedure. A basic
      feature of the method is that automatically larger samples are obtained if
      accessions are further apart and smaller samples if accessions are closer
      together. Genetic distance sampling can be used in conjunction with predefined
      stratifications of the accessions. Sample sizes are determined automatically;
      they depend on the distances between accessions within strata. The method is
      applied to the collection of cultivated lettuce of the Centre for Genetic
      Resources, the Netherlands. In this paper, genetic distances between accessions
      are obtained using AFLP marker data. However, genetic distance sampling can be
      applied using any measure of genetic distance between accessions. Some properties
      of genetic distance sampling are discussed.

PMID- 17180378
TI  - The genetics of nitrogen use in hexaploid wheat: N utilisation, development and
      yield.
AB  - A genetic study is presented for traits relating to nitrogen use in wheat.
      Quantitative trait loci (QTLs) were established for 21 traits relating to growth,
      yield and leaf nitrogen (N) assimilation during grain fill in hexaploid wheat
      (Triticum aestivum L.) using a mapping population from the cross Chinese Spring x
      SQ1. Glutamine synthetase (GS) isozymes and estimated locations of 126 genes were
      placed on the genetic map. QTLs for flag leaf GS activity, soluble protein,
      extract colour and fresh weight were found in similar regions implying shared
      control of leaf metabolism and leaf size. Flag leaf traits were negatively
      associated with days to anthesis both phenotypically and genetically,
      demonstrating the complex interactions of metabolism with development. One QTL
      cluster for GS activity co-localised with a GS2 gene mapped on chromosome 2A, and
      another with the mapped GSr gene on 4A. QTLs for GS activity were invariably co
      localised with those for grain N, with increased activity associated with higher
      grain N, but with no or negative correlations with grain yield components.
      Peduncle N was positively correlated, and QTLs co-localised, with grain N and
      flag leaf N assimilatory traits, suggesting that stem N can be indicative of
      grain N status in wheat. A major QTL for ear number per plant was identified on
      chromosome 6B which was negatively co-localised with leaf fresh weight, peduncle
      N, grain N and grain yield. This locus is involved in processes defining the
      control of tiller number and consequently assimilate partitioning and deserves
      further examination.

PMID- 17180379
TI  - Hybrid maize breeding with doubled haploids: II. Optimum type and number of
      testers in two-stage selection for general combining ability.
AB  - Optimum allocation of test resources is of crucial importance for the efficiency
      of breeding programs. Our objectives were to (1) determine the optimum allocation
      of the number of lines, test locations, as well as number and type of testers in
      hybrid maize breeding using doubled haploids with two breeding strategies for
      improvement of general combining ability (GCA), (2) compare the maximum selection
      gain (DeltaG) achievable under both strategies, and (3) give recommendations for
      the optimum implementation of doubled haploids in commercial hybrid maize
      breeding. We calculated DeltaG by numerical integration for two two-stage
      selection strategies with evaluation of (1) testcross performance in both stages
      (BS1) or (2) line per se performance in the first stage followed by testcross
      performance in the second stage (BS2). Different assumptions were made regarding
      the budget, variance components (VCs), and the correlation between line per se
      performance and GCA. Selection gain for GCA increased with a broader genetic base
      of the tester. Hence, testers combining a large number of divergent lines are
      advantageous. However, in applied breeding programs, the use of single- or double
      cross testers in the first and inbred testers in the second selection stage may
      be a good compromise between theoretical and practical requirements. With a
      correlation between line per se performance and GCA of 0.50, DeltaG for BS1 is
      about 5% higher than for BS2, if an economic weight of line per se performance is
      neglected. With increasing economic weight of line per se performance, relative
      efficiency of BS2 increased rapidly resulting in a superiority of BS2 over BS1
      already for an economic weight for line per se performance larger than 0.1.
      Considering the importance of an economic seed production, an economic weight
      larger than 0.1 seems realistic indicating the necessity of separate breeding
      strategies for seed and pollen parent heterotic groups.

PMID- 17180380
TI  - Herpes simplex and varicella-zoster virus infections during pregnancy: current
      concepts of prevention, diagnosis and therapy. Part 2: Varicella-zoster virus
      infections.
AB  - Varicella during pregnancy can be associated with severe illnesses for both the
      mother and her neonate. Varicella pneumonia must be regarded as a medical
      emergency, since pregnant women are at risk of life-threatening ventilatory
      compromise and death. After maternal chickenpox in the first and second
      trimesters, congenital varicella syndrome may occur in nearly 2% of the cases.
      The characteristic symptoms consist of skin lesions in dermatomal distribution,
      neurological defects, eye diseases and skeletal anomalies. If the mother develops
      varicella rashes between day 4 (5) antepartum and day 2 postpartum, generalized
      neonatal varicella leading to death in about 20% of the cases has to be expected.
      Normal zoster has not been shown to be associated with maternal pneumonia, birth
      defects or problems in the perinatal period. On the basis of the clinical
      consequences of varicella-zoster virus infections during pregnancy, the present
      paper summarizes the currently available concepts of prevention, diagnosis and
      therapy.

PMID- 17180381
TI  - Volatiles of bacterial antagonists inhibit mycelial growth of the plant pathogen
      Rhizoctonia solani.
AB  - Bacterial antagonists are bacteria that negatively affect the growth of other
      organisms. Many antagonists inhibit the growth of fungi by various mechanisms,
      e.g., secretion of lytic enzymes, siderophores and antibiotics. Such inhibition
      of fungal growth may indirectly support plant growth. Here, we demonstrate that
      small organic volatile compounds (VOCs) emitted from bacterial antagonists
      negatively influence the mycelial growth of the soil-borne phytopathogenic fungus
      Rhizoctonia solani Kuhn. Strong inhibitions (99-80%) under the test conditions
      were observed with Stenotrophomonas maltophilia R3089, Serratia plymuthica HRO
      C48, Stenotrophomonas rhizophila P69, Serratia odorifera 4Rx13, Pseudomonas
      trivialis 3Re2-7, S. plymuthica 3Re4-18 and Bacillus subtilis B2g. Pseudomonas
      fluorescens L13-6-12 and Burkholderia cepacia 1S18 achieved 30% growth reduction.
      The VOC profiles of these antagonists, obtained through headspace collection and
      analysis on GC-MS, show different compositions and complexities ranging from 1 to
      almost 30 compounds. Most volatiles are species-specific, but overlapping
      volatile patterns were found for Serratia spp. and Pseudomonas spp. Many of the
      bacterial VOCs could not be identified for lack of match with mass-spectra of
      volatiles in the databases.

PMID- 17180382
TI  - [Diagnostic management of children with craniocerebral trauma].

PMID- 17180384
TI  - A public-private analysis of the new Dutch health insurance system.

PMID- 17180385
TI  - Estimation and comparison of ostomy appliance costs with tariffs in Belgium.
AB  - This study estimated costs of production and distribution of ostomy appliances,
      and compared cost estimates with tariffs in Belgium. The cost model took into
      account manufacturing costs, overhead, R&D, warehousing, profits, and
      distribution margins. Data were derived from manufacturers, a decomposition of
      finished products, and interviews with stakeholders. The cost model generated
      estimated retail prices of euro 2.96 for one-piece appliances, euro 1.62 for two
      piece pouches, and euro 2.06 for two-piece flanges. Production and distribution
      costs accounted for 40 and 60% of retail prices, respectively. Estimated retail
      prices corresponded well with tariffs for one-piece appliances and for two-piece
      pouches. For two-piece regular flanges, a substantial difference was observed
      between the calculated price of euro 2.06 and the tariffs of euro 6.05. In the
      absence of publicly disclosed information on the cost structure of appliances,
      estimating ostomy appliance costs is valuable to reimbursement agencies when
      setting tariffs.

PMID- 17180383
TI  - [Trauma of the spine and intervertebral disk. A challenge for the expert in
      compensation claims after sustained "trifle trauma"].
AB  - In the literature, the association between chronic pain syndromes of the spine
      and sustained "trifle trauma" is a matter of controversy. "Trifle trauma" is
      identified as a contusion, compression and/or sprain without a definite, acute
      imaging sign of injury to the bone, the disk or the ligaments of the spine. Most
      of the time, striking isolated changes to the intervertebral disks are
      interpreted as preexisting without relevance to an acute injury. However, complex
      chronic pain syndromes causing permanent and significant functional limitations
      in daily life and work may occur. Besides the diagnostic and therapeutic
      challenge for the treating physician, the expert confronted with compensation
      claims very often has to answer questions as to whether "trifle trauma" of the
      spine may lead to significant and permanent functional limitations or loss with
      chronic pain syndromes, and what the importance of possible isolated changes in
      intervertebral disks is. The data from literature dealing with this topic is
      contradictory and deficient. In this article, we critically examine the causality
      between "trifle trauma" to the spine and possible permanent chronic complaints
      based on currently available data from the literature in order to support the
      process of decision making in questions of litigation and controversial
      compensation claims.

PMID- 17180386
TI  - [A new technique for transcrestal sinus floor elevation with press-fit bone
      cylinders (dowel lift): short communication of the first in vitro results].
AB  - The minimally invasive sinus floor elevation as first described by Summers is
      limited in augmentation volume, whereas a more invasive approach is required for
      the technique of Tatum for larger bone defects. We developed a new technique for
      the transcrestal elevation of the sinus floor with bone dowels using a press-fit
      technique (dowel lift). We present the technique with first in vitro results in a
      fresh, unpreserved, human cadaver.

PMID- 17180387
TI  - Thrombotic thrombocytopenic purpura secondary to mifepristone in a patient of
      medical termination in early pregnancy.

PMID- 17180388
TI  - The effect of hydroxyurea on P-glycoprotein/BCRP-mediated transport and CYP3A
      metabolism of imatinib mesylate.
AB  - PURPOSE: It has been reported that the combination therapy of imatinib mesylate,
      a tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase
      inhibitor, is associated with remarkable antitumor activity in patients with
      recurrent glioblastoma multiforme. However, the mechanism of the added activity
      of hydroxyurea to imatinib is not known. The purpose of this study was to
      investigate in vitro, whether hydroxyurea could enhance the central nervous
      system penetration of imatinib, by inhibition of the ATP-dependent transporter
      proteins P-glycoprotein (ABCB1; MDR1; Pgp) and Breast Cancer Resistance Protein
      (ABCG2; BCRP), or by inhibition of cytochrome P450 3A (CYP3A) metabolism of
      imatinib. METHODS: The effect of hydroxyurea on the Pgp and BCRP mediated
      transport of imatinib was investigated by the sulforhodamine-B (SRB) drug
      cytotoxicity assay and transepithelial transport assay. In vitro
      biotransformation studies with supersomes expressing human CYP3A4 were performed
      to investigate whether hydroxyurea inhibited CYP3A4. RESULTS: In both in vitro
      cytotoxicity and transport assays, hydroxyurea did not affect Pgp and BCRP
      mediated transport of imatinib. In a biotransformation assay, hydroxyurea had no
      influence on the metabolic degradation of imatinib either. CONCLUSION: The
      results indicate that hydroxyurea does not interact with imatinib by inhibition
      of Pgp and BCRP mediated transport or by CYP3A4 mediated metabolism of imatinib.

PMID- 17180389
TI  - Unexpected superimposition of nutcracker effect in various conditions: is it an
      unrecognized confounding factor? Comment on: Henoch-Schonlein purpura presenting
      duodenal involvement similar to superior mesenteric artery syndrome in a girl.
      (Eur J Pediatr. 2006 Sep 29; [Epub ahead of print]).

PMID- 17180390
TI  - Redo transanal endorectal pull-through: a preliminary study.
AB  - The aim of this study is to evaluate the safety and efficacy of the redo
      transanal endorectal pull-through (TEPT) for patients with persistent symptoms
      after pull-through for Hirschsprung's disease (HD). Seven children were included
      in the study, their ages ranged from 2.5 to 6 years (four males and three
      females). They presented with persistent obstructive symptoms after pull-through
      for HD, which was remediated with redo TEPT. Indications were persistent
      constipation, anastomotic stricture unresponsive to dilatation with or without
      attacks of enterocolitis. Mean follow-up period was 12 months (ranged from 8 to
      16 months). Obstructive symptoms were relieved in all patients with no soiling
      throughout the period of follow-up. Enterocolitis developed once in two patients
      who responded to conservative management after hospitalization. There were no
      deaths and anastomotic leakage, persistent stricture and cuff abscess did not
      develop in our series. EMG mapping of the external anal sphincter showed a good
      resting and powerful squeezing pressure curve. Redo TEPT is a useful alternative
      procedure for persistent symptoms of HD, and it appears to be safe and effective.

PMID- 17180392
TI  - Euthanasia: a word no longer to be used or abused.

PMID- 17180391
TI  - Year in review in Intensive Care Medicine, 2006. I. Experimental studies.
      Clinical studies: brain injury, renal failure and endocrinology.

PMID- 17180393
TI  - Lipopolysaccharide induces sCD40L release through human platelets TLR4, but not
      TLR2 and TLR9.

PMID- 17180394
TI  - The current status of palliative care teams in Japanese university hospitals: a
      nationwide questionnaire survey.
AB  - GOAL: Although the importance of the palliative care team (PCT) to university
      hospitals is widely accepted, the issues of palliative care at the national level
      have not been clarified. We conducted a nationwide survey of the current status
      of PCTs in all (123) Japanese university hospitals. MATERIALS AND METHODS: In
      2003, 2004 and 2005, the authors conducted a self-reporting cross-sectional
      survey. Questionnaires were mailed to nursing directors and selected PCT members
      of all Japanese university hospitals. RESULTS: Of 123 hospitals in 2005, 99 (80%)
      returned the questionnaire; 33% used PCTs, and 11% used certified PCTs. Our
      findings include: annual number of patients treated by PCTs (83/70 +/- 64,
      mean/median +/- SD), daily number of patients treated by PCTs (12/11 +/- 14), and
      days of PCT care per patient (30/30 +/- 22). Certified PCTs treated more patients
      per year (p = 0.004) and more patients per day (p < 0.001) compared to
      noncertified PCTs. Over the 3-year period, the number of hospitals utilizing PCTs
      only slightly increased (2003: 27%, 2004: 29%, 2005: 33%), as did those using
      certified PCTs (2003: 3%, 2004: 9%, 2005: 11%). In 2005, the reasons for
      noncertification of PCTs included "lack of physicians who specialize in
      palliative care (82%)" and "lack of nurses who specialize in palliative care
      (56%)." CONCLUSIONS: The entire system of palliative care in Japanese university
      hospitals is currently insufficient. The lack of physicians and nurses who
      specialize in palliative care is a significant barrier, and therefore, the
      initiation of a formal training system for these health care professionals is a
      high priority issue.

PMID- 17180395
TI  - [Impact factors and publication time spans in urological journals].
AB  - The impact factor, cited half-life, and immediacy index are three important
      methods that can be used to demonstrate how a journal's articles are cited over
      the course of a specific time span. These three factors thus represent
      instruments for measuring the importance and reputation of a scientific magazine.
      The goal of our study was to evaluate the constancy of journals specialized in
      the field of urology and to analyze those listed in the 2005 Journal Citation
      Report (JCR) using the standardized methods specified by the Institute of
      Scientific Information (ISI) and JCR. Primarily we wanted to examine the
      different time spans needed for publication of original papers submitted to
      certain journals; in more exact terms: the time span from submission of an
      article or original paper to its publication and from the time of acceptance of
      an original paper or article to its publication in a urological journal.
      Furthermore, we wanted to investigate the dynamics of urological journals
      regarding their impact factors for the years 2000-2005. The study was performed
      using the ISI JCR and the library as well as the online library of the Friedrich
      Alexander University in Erlangen. A very satisfactory development can be observed
      in the field of urology with the standardized methods of the (ISI) JCR.

PMID- 17180396
TI  - [Ureteral rupture when changing a suprapubic vesical catheter].
AB  - We describe, for the first time, a rupture of the ureter caused by changing a
      suprapubic vesical catheter. The guide wire passed into the ostium of the left
      ureter during the procedure, and the catheter was pushed over the wire into the
      left ureter blocking it. The lesion was diagnosed by intravenous pyelography. A
      pigtail stent was placed in the left ureter.

PMID- 17180398
TI  - Coordinate system representations of movement direction in the premotor cortex.
AB  - Recently, we compared the encoding of movement direction in primary motor cortex
      (MI) under three coordinate systems, an extrinsic cartesian (CA), an intrinsic
      joint angle (JA), and an intermediate shoulder-centered (SC) and found that no
      single coordinate system was uniquely represented in MI. Here we extend this
      investigation to the premotor area which is regarded as a major source of input
      to the MI. Multiple single units were simultaneously recorded from the caudal
      portions of dorsal premotor (PMd) and ventral premotor (PMv) cortices as a
      behaving monkey moved its hand over the horizontal work space. We compared the
      mutual information between the neuronal firing rate of each unit and hand
      movement direction under each of the three coordinate systems. As in the MI
      study, the results showed that there was no evidence for a unique coordinate
      system representation. There was a bias towards the SC system in PMd, albeit
      weaker than the SC bias observed in MI. In PMv, there was a strong bias for both
      SC and JA coordinate systems as compared to a CA coordinate system. These results
      provided further evidence against a unique coordinate system for movement
      direction within the motor cortex. However, the directional information within
      both PMd and PMv was significantly less than that of MI suggesting that factors
      other than the detailed motion of the arm account for much of the variance of
      activity within the premotor cortex.

PMID- 17180399
TI  - Concomitant fracture of bilateral occipital condyle and inferior clivus: what is
      the mechanism of injury?
AB  - With the routine use of multi-slice high resolution computed tomography,
      increasing number of occipital condyle fractures have been reported in the last
      decade. The authors report a very rare case of bilateral occipital condyle
      fracture complicated by the fracture of the inferior clivus and discuss the
      possible mechanisms of injury.

PMID- 17180400
TI  - Headache in patients with cervical radiculopathy: a prospective study with
      selective nerve root blocks in 275 patients.
AB  - Since many years we routinely use diagnostic selective nerve root blocks (SNRB)
      at our department when evaluating patients with cervical radiculopathy.
      Frequently patients who also presented with headache reported that the headache
      disappeared when the nerve root responsible for the radicular pain was blocked
      with local anaesthetics. Headache has been described as a companioning symptom
      related to cervical radiculopathy but has never before been evaluated with SNRB
      performed in the lower cervical spine. For this reason we added to our routine an
      evaluation of the response from the SNRB on headache in patients with cervical
      radiculopathy. The aim was to describe the frequency of headache in patients with
      cervical radiculopathy and its response to a selective nerve root block of the
      nerve root/roots responsible for the radiculopathy. Can nerve root compression in
      the lower cervical spine produce headache? In this consecutive series of 275
      patients with cervical radiculopathy, 161 patients reported that they also
      suffered from daily or recurrent headache located most often unilaterally on the
      same side as the radiculopathy. All patients underwent a careful clinical
      examination by a neurosurgeon and a MRI of the cervical spine. The significantly
      compressed root/roots, according to the MRI, underwent SNRB with a local
      anaesthetic. The effect of the nerve root block on the radiculopathy and the
      headache was carefully noted and evaluated by a physiotherapist using visual
      analogue scales (VAS) before and after the SNRB. All patients with headache had
      tender points in the neck/shoulder region on the affected side. Patients with
      headache graded significantly more limitations in daily activities and higher
      pain intensity in the neck/shoulder/arm than patients without headache. After
      selective nerve root block, 59% of the patients with headache reported 50% or
      more reduction of headache and of these 69% reported total relief. A significant
      correlation was seen between reduced headache intensity and reduced pain in the
      neck, shoulder and arm. The result indicates that cervical root compression from
      degenerative disease in the lower cervical spine producing radiculopathy might
      also induce headache.

PMID- 17180401
TI  - Analysis of anatomic morphometry of the pedicles and the safe zone for through
      pedicle procedures in the thoracic and lumbar spine.
AB  - Posterior instrumentation through the pedicle is a common surgery. Understanding
      the morphometry of the pedicle and the anatomy of adjacent neural structures
      should help decrease the risk of postoperative complications. T1-L5 segments from
      15 sets of human vertebrae were separated into individual vertebrae and the
      morphometric characteristics of the thoracic and lumbar spine and the safe zone
      of the pedicle were analyzed. T11-L5 segments from six human cadavers were
      dissected. Measurements were taken from the pedicle to the dura and nerve roots
      superiorly, inferiorly, medially, and laterally, and the transverse angles of the
      nerve roots were measured. Pedicles were widest in L5 and narrowest in T4 in the
      transverse plane, and widest in T11 or T12 and narrowest in T1 in the sagittal
      plane. In individual pedicle, the ranges of the safe zone width and height were
      3.4-7.7 and 8.6-13.7 mm, respectively, in T1-T10; and 7.2-17.8 and 13.9-16.7 mm,
      respectively, in T11-L5. The transverse angle of the pedicle decreases
      progressively from T1 to T12, then increase from L1 to L5. In sagittal angle, the
      largest angle localized at T2 and the smallest at L5. The mean distances from
      pedicles to adjacent neural structures were greater superiorly and laterally than
      inferiorly and medially. The lateral distance between nerve root and the pedicle
      ranged from 2.4 to 9.6 mm in lumbar spine. This study provides potential safe
      zones for the application of through-pedicle procedures to help decrease the risk
      of postoperative complications.

PMID- 17180402
TI  - Variation in articular cartilage in rats between 3 and 32 months old. A
      histomorphometric and scanning electron microscopy study.
AB  - In this study we assess the thickness, the cellular density, the cell sizes and
      the collagen of the three superficial cartilage zones and the morphology of the
      articular surface of the femoral trochlea in rats with 3, 12 and 32 months of
      age. The cartilage was studied using light microscopy and scanning electron
      microscopy. The quantitative results are expressed as means +/- SEM. The data
      were compared statistically (P < 0.05). Both the thickness and the cellular
      density significantly diminish with age, in the three cartilage zones studied.
      The reduction of cellular density is more pronounced in the superficial and
      intermediate zones of the cartilage (zones I and II, respectively). In zone III
      (deep zone), the cellular density declines only as from 12 months of age. The
      area of the chondrocytes diminishes in the superficial and deep zones, but only
      as from 12 months old. In the intermediate zone, there is no chondrocyte
      hypotrophy with age. The types of collagen in the zones of the cartilage change
      with age. In the superficial zone, the collagen type I predominates at 3 months
      of age while the collagen type II predominates at 12 and 32 months of age. In the
      intermediate and deep zones, the collagen type I that predominates at 3 months of
      age is substituted by the collagen type III at 12 and 32 months of age. The
      articular surface in the 3-month-old rats is relatively smooth, presenting few
      undulations. In 12-month-old animal cartilages, few fissures and craters are
      found. In the 32-month-old animals, it was observed a higher number of this kind
      of degenerative changes and with a more severe look.

PMID- 17180403
TI  - Seasonal variability of heavy metals in surface sediment of Lake Sapanca, Turkey.
AB  - Lake Sapanca is exposed to heavy urbanization and industrialization because of
      its natural beauty and its proximity to the metropolitan Istanbul, Turkey. In
      this study, it was aimed to investigate seasonal changes of some heavy metals
      (Pb, Cr, Cu, Mn, Ni, Zn and Cd) concentration of surface sediment. Nine different
      stations were chosen as sampling points. Samples were taken every three months
      and the seasonal and annual average concentration of the elements were
      determined. Seasonal highest values of heavy metals were observed as follows; Cr,
      Cu, Mn, Ni and Zn in Summer, Cd in Autumn. There was no seasonal difference for
      Pb, Cr and Cd. It seems that Lake Sapanca has not been polluted yet. However, it
      was found that Cu and Ni concentrations in surface sediment exceed lowest effect
      level.

PMID- 17180404
TI  - Multivariate analysis of interactions between phytoplankton biomass and
      environmental variables in Taihu Lake, China.
AB  - Phytoplankton variation in large shallow eutrophic lakes is characterized by high
      spatial and temporal heterogenity. Understanding the pattern of phytoplankton
      variation and the relationships between it and environmental variables can
      contribute to eutrophic lakes management. In this study Taihu Lake, one of the
      largest eutrophic fresh water lake in China, was taken as study area. The water
      body of Taihu Lake was divided into five regions viz. Wuli bay (WB), Meilian Bay
      (MB), West Taihu Lake (WTL), Main Body of Taihu Lake (MBTL) and East Taihu Lake
      (ETL). Concentrations of chlorophyll-a and the related environmental variables
      were determined in each region in the period 2000-2003. Factor analysis and
      multivariate analysis were applied to evaluate the interactions between
      phytoplankton variation and environmental variables. Results showed that the
      highest average concentrations of TN, TP and Chl-a were observed in WB, followed
      in a descending order by MB and WTL, and the lowest concentrations of TN, TP and
      Chl-a were observed in MBTL and ETL. Chl-a and TP concentrations in most regions
      (except ETL) declined during the study period. It suggested that to some extent
      the lake was recovering from eutrophication. However, persistent ascending of TN
      and NH(4)-N in all five regions indicated the deteriorating of water quality in
      the study period. Results of multivariate showed that the relationships between
      phytoplankton biomass and environmental variables varied among regions. TP
      illustrated itself a controlling role on phytoplankton in WB, MB, WTL and MBTL
      according to the significant positive relations to phytoplankton biomass in these
      regions. Nitrogen could be identified as a limiting factor to phytoplankton
      biomass in ETL in view of the positive correlations between TN and phytoplankton
      and between NH(4)-N and phytoplankton. Spatial variation of interactions between
      phytoplankton and environmental parameters suggested proper eutrophication
      control measures were needed to restore ecological system in each region of Taihu
      Lake.

PMID- 17180405
TI  - Diel cycling of zinc in a stream impacted by acid rock drainage: initial results
      from a new in situ Zn analyzer.
AB  - Recent work has demonstrated that many trace metals undergo dramatic diel (24-h)
      cycles in near neutral pH streams with metal concentrations reproducibly changing
      up to 500% during the diel period (Nimick et al., 2003). To examine diel zinc
      cycles in streams affected by acid rock drainage, we have developed a novel
      instrument, the Zn-DigiScan, to continuously monitor in situ zinc concentrations
      in near real-time. Initial results from a 3-day deployment at Fisher Creek,
      Montana have demonstrated the ability of the Zn-DigiScan to record diel Zn
      cycling at levels below 100 microg/l. Longer deployments of this instrument could
      be used to examine the effects of episodic events such as rainstorms and snowmelt
      pulses on zinc loading in streams affected by acid rock drainage.

PMID- 17180406
TI  - Characterization of volatile organic compounds (VOCs) and their sources in the
      air of Izmir, Turkey.
AB  - Air samples were collected in Izmir, Turkey at two (suburban and urban) sites
      during three sampling programs in 2002 and 2004 to determine the ambient
      concentrations of several monoaromatic, chlorinated and oxygenated volatile
      organic compounds (VOCs). Samples were analyzed for 60 VOCs using gas
      chromatography/mass spectrometry and 28 compounds were detected in most samples.
      On the average, urban air VOC concentrations were about four times higher than
      those measured at the suburban site. Toluene (40.6%) was the most abundant
      compound in suburban site and was followed by benzene (7.4%), o,m-xylene (6.5%),
      and 1,2-dichloroethane (5.1%). In urban site, toluene (30.5%), p-xylene (14.9%),
      o,m-xylene (11.4%), and ethyl benzene (7.2%) were the dominating compounds in
      summer. In winter, toluene (31.1%), benzene (23.9%), 1,2-dichloroethane (9.5%),
      and o,m-xylene (8.2%) were the most abundant compounds. Receptor modeling
      (positive matrix factorization) has been performed to estimate the contribution
      of specific source types to ambient concentrations. Six source factors (gasoline
      vehicle exhaust, diesel vehicle exhaust+residential heating, paint
      production/application, degreasing, dry cleaning, and an undefined source) were
      extracted from the samples collected in the urban site. Three source factors
      (gasoline vehicle exhaust, diesel vehicle exhaust, and paint
      production/application) were identified for the suburban site.

PMID- 17180408
TI  - Comparative on causes and accumulation of selenium in the tree-rings ambient high
      selenium coal combustion area from Yutangba, Hubei, China.
AB  - Toxic trace elements emitted during coal combustion are the main sources of air
      pollution. They are released into the atmosphere mainly in the forms of fine ash,
      smoke and flue, and thus adversely affect plant, animal and human health.
      Selenium is one of toxic and the most volatile in coal. Large amount of
      atmospheric emission of selenium, as well as selenium present and scrubber
      stockpiles in ash may create serious environmental problems. In the paper, on the
      basis of investigating the abundance and distribution of selenium in plant-rings
      during recent 20 years, the bioaccumulation of selenium is explained that
      selenium in plant, which were collected from the village of selenium-rich coal
      combustion, is much higher than that in plants collected away from the village of
      selenium-rich coal combustion. The main origins of selenium are selenium-rich
      coal combustion and high-selenium rock weathered. The selenium recycle by food
      chain and selenium will accumulate and redistribute in environments.

PMID- 17180407
TI  - Particle-phase polycyclic aromatic hydrocarbon emissions from non-catalysed, in
      use four-stroke scooters.
AB  - The emissions of particle-phase polycyclic aromatic hydrocarbons (PAHs) were
      evaluated in the exhaust of four (two EURO-0 and two EURO-1) four-stroke engine,
      in-use scooters with displacement of 150 cc, which were not equipped with
      catalytic converters. Non-catalysed motorcycles still represent a large
      proportion of circulating two-wheelers in Italy and, possibly, also in other
      countries. Tests were performed on a dynamometer bench, using the ECE-40 test
      cycle procedure. Particulate matter into the exhaust emissions was collected both
      during the "hot" phase of the ECE-40 driving cycle and including the first two
      elementary cycles of engine warming-up heating (whole cycle). Fourteen PAHs were
      quantified and total PAH emission factors (Sigma PAH) ranged from 7 to 169 microg
      km(-1). Expressed in benzo(a)pyrene equivalent (BaP(eq)), emission factors ranged
      from 0.6 to 18 microg km(-1). Results from the tested scooters show that despite
      their small engine size, non-catalysed motorcycles can emit amounts of
      particulate PAHs that can be comparable or even higher than emissions reported
      elsewhere from gasoline- and diesel-powered passenger cars and light- and heavy
      duty vehicles. In countries where a large number of non-catalysed motorcycles are
      circulating, PAH emissions in urban areas from this class of vehicles might be of
      the same order of magnitude of emissions from diesel passenger cars.

PMID- 17180409
TI  - Sampling and analysis of quaternary ammonium compounds (QACs) traces in indoor
      atmosphere.
AB  - Quaternary Ammonium Compounds (QACs) are widely found in disinfectants used in
      hospitals. Benzalkonium chloride (BAC) and didecyldimethylammonium chloride
      (DDAC) predominate in the disinfecting formulations. These compounds are strong
      irritants and can play a role in the induction of Occupational Asthma among the
      professionals of health and cleaning. In order to evaluate the potential health
      effect of these quaternary ammonium compounds to hospital employers, the
      development of an analytical method for their quantification in indoor air was
      developed. DDAC aerosols are trapped by adsorption on XAD-2 resin SKC tube. The
      air in hospital buildings was sampled using a constant debit Gillian pump at a
      flow of 1.0 l/min (+/-5%). Ion Chromatography (IC) was chosen for the analysis of
      DDAC especially for its high sensitivity and specificity. The Limit of Detection
      (LOD) by IC for DDAC is 0.56 mug/ml. Therefore the LOD of atmospheric DDAC is 28
      microg/m(3) with an air volume of 100 l and a desorption volume of 5 ml. All DDAC
      air samples were lower than the LOD of the analytical method by IC. Under the
      standard conditions of use of the disinfecting solutions (Surfanios, Ampholysine
      Plus and Amphospray 41), the insignificant volatility of DDAC would not seem to
      be able to contaminate the indoor hospital atmosphere during the disinfection
      process. However, the DDAC can contaminate working atmospheres if it is put in
      suspension by aerosolisation.

PMID- 17180410
TI  - Leaf litterbag sampling for larval plethodontid salamander populations in
      Georgia.
AB  - Survey techniques for larval salamanders vary in their effectiveness and
      efficiencies. In this study, the leaf litterbag sampling technique was employed
      to gather data on larval salamander populations in perennial streams of southern
      Georgia. Salamanders were collected monthly for 12 months to analyze capture
      counts and population size-class structure. Simultaneous dipnet sweep data were
      used to examine potential count data biases of the leaf litterbag sampling
      technique. In both leaf litterbag and dipnet sweep surveys, adult and larval
      Southern Two-lined Salamanders (Eurycea cirrigera) and larval Southern Red
      Salamanders (Pseudotriton ruber) were sampled. In leaf litterbags, larval E.
      cirrigera were captured most frequently, followed by adult E. cirrigera and
      larval P. ruber, respectively. However, the efficiency of collecting adult E.
      cirrigera and larval P. ruber could not be determined because of small sample
      sizes. Larval E. cirrigera counts detected from leaf litterbags were frequently
      lower than those associated with dipnet sweeps, suggesting that the former may
      underestimate larval salamander counts. Leaf litterbags successfully detected all
      E. cirrigera size-classes (i.e., first-year, second-year, and adult), further
      indicating that larvae in Georgia spend 2 years in the aquatic phase. Leaf
      litterbags are an effective method of sampling larval salamanders when used to
      assess species assemblage and age-class distribution.

PMID- 17180411
TI  - C2-C6 background hydrocarbon concentrations monitored at a roof top and green
      park site, in Dublin City centre.
AB  - A 5 week monitoring campaign was carried out in Dublin City centre, to establish
      which site gave a more accurate background city centre estimation: a roof-top or
      green field site. This background represented a conservative estimate of HC
      exposure in Dublin City centre, useful for quantifying health effects related to
      this form of pollution and also for establishing a local background relative to
      the four surrounding main roads when the wind direction is travelling towards
      each road with the background receptor upwind. Over the entire monitoring
      campaign, the lowest concentrations and relative standard deviations were
      observed at the green field site, regardless of time of day or meteorological
      effects.

PMID- 17180412
TI  - Hydrocarbon uptake by roots of Vicia faba (Fabaceae).
AB  - Vicia faba was grown in crude oil polluted soil and its roots were extracted for
      the detection and estimation of hydrocarbons. Saturated and unsaturated Aliphatic
      Hydrocarbons (AHs) ranging from C(22) to C(36) were identified in AHs fraction.
      However, PAHs were not present in the same extract. This could be due to the fact
      that PAHs being toxic compounds are not accumulated in the plant root extracts of
      V. faba grown in crude oil polluted soil. Three phytoalexins were identified and
      estimated by mass spectrometric analysis in the root extracts of V. faba. These
      three compounds are 2-t-butyl-4-(dimethyl benzyl) phenol, 2, 4-bis (dimethyl
      benzyl) phenol and 2,4-bis (dimethyl benzyl)-6-butyl phenol. These phenolics in
      V. faba are being reported for the first time. These compounds are presumably
      elicited as a direct stress on crude oil hydrocarbons on the roots of this plant.

PMID- 17180413
TI  - Spatial distribution and temporal change of carbon storage in timber biomass of
      two different forest management units.
AB  - Forests make up large ecosystems and can play an important role in mitigating the
      emissions of CO2, the most important greenhouse gas. However, they are sources of
      atmospheric carbon when they are disturbed by human or natural causes. Storage of
      carbon through expansion and adaptive management of forest ecosystems can assist
      in reducing carbon concentrations in atmosphere. This study proposes a
      methodology to produce spatially explicit estimates of the carbon storages
      (aboveground plus belowground) depending on land use/cover changes in two
      different forest ecosystems during various periods. Carbon storages for each
      forest ecosystem were projected according to inventory data, and carbon storages
      were mapped in a geographic information system (GIS). Results showed that total
      carbon stored in above and belowground of both forest ecosystems increased from
      one period to other because of especially increase of productive forest areas and
      decline of degraded forest areas as well as protection of spruce forests subject
      to insect attacks.

PMID- 17180414
TI  - Solid phase extraction of gold(III) on Amberlite XAD-2000 prior to its flame
      atomic absorption spectrometric determination.
AB  - A solid phase extraction method for the determination of gold(III) at trace
      levels by flame atomic absorption spectrometer (FAAS) was developed. The method
      was based on retention of gold as chloro complexes through the Amberlite XAD
      2000. The effect of some analytical parameters including hydrochloric acid
      concentration, sample volume, sample and eluent flow rates, eluent volume, eluent
      concentration and interfering ions on the recovery of gold(III) was investigated.
      The retention of gold(III) from 1.5 mol l(-1) HCl solution and the recovery of
      gold with 0.07 mol l(-1) NH3 solution were quantitative (>or=95%). The relative
      standard deviation (RSD) was calculated as 3.2% (n = 10). The detection limit for
      gold was 2 microg l(-1). The accuracy was checked with the determination of gold
      spiked an artificial seawater and a pure copper samples.

PMID- 17180415
TI  - Hydrogeochemistry and groundwater quality assessment of lower part of the
      Ponnaiyar River Basin, Cuddalore district, South India.
AB  - The Lower Ponnaiyar River Basin forms an important groundwater province in South
      India constituted by Tertiary formations dominated by sandstones and overlain by
      alluvium. The region enjoyed artesian conditions 50 years back but at present
      frequent failure of monsoon and over exploitation is threatening the aquifer.
      Further, extensive agricultural and industrial activities and urbanization has
      resulted in the increase in demand and contamination of the aquifer. To identify
      the sources and quality of groundwater, water samples from 47 bore wells were
      collected in an area of 154 km2 and were analysed for major ions and trace
      metals. The results reveal that the groundwater in many places is contaminated by
      higher concentrations of NO3, Cl, PO4 and Fe. Four major hydrochemical facies Ca
      Mg-Cl, Na-Cl, Ca-HCO3 and Na-HCO3 were identified using Piper trilinear diagram.
      Salinity, sodium adsorption ratio, and sodium percentage indicate that most of
      the groundwater samples are not suitable for irrigation as well as for domestic
      purposes and far from drinking water standards. The most serious pollution threat
      to groundwater is from nitrate ions, which are associated with sewage and
      fertilizers application. The present state of the quality of the lower part of
      Ponnaiyar River Basin is of great concern and the higher concentration of toxic
      metals (Fe and Ni) may entail various health hazards.

PMID- 17180416
TI  - Temporal variations of airborne particles concentration in the Brussels
      environment.
AB  - We report and analyze data on the PM10 fraction of airborne particles measured at
      five recording stations in the Brussels region from October 2002 till September
      2003. These stations are representative of the various activity sectors of the
      Brussels urban area. The objective was the determination of the origin of the
      PM10 particles (particles up to 10 mum) that are recorded in that region in order
      to follow the EU directives concerning tolerance level of airborne particles
      concentration. In order to evaluate the impacts of local and external factors
      that inject solid particles in the atmosphere of Brussels we compared
      concentration data from working and not working (holidays) periods. Moreover, we
      also compared concentrations from periods of agricultural activity and rest in
      the Brabant provinces surrounding the Brussels region for various crop types. The
      results lead to the conclusion that the impact or urban traffic is rather limited
      while that of the agricultural activities is important. Moreover, there appears a
      clear-cut distinction between different types of crops.

PMID- 17180417
TI  - Alterations in the levels of ions in blood and liver of freshwater fish, Cyprinus
      carpio var. communis exposed to dimethoate.
AB  - The fingerlings of Cyprinus carpio var. communis were exposed to sublethal
      concentration of dimethoate for 7, 14 days to evaluate the impact of the
      pesticide dimethoate on different ions namely sodium, potassium, chloride,
      calcium, magnesium. The blood potassium, calcium, magnesium and liver chloride
      and magnesium levels were elevated under sublethal condition. The blood sodium,
      chloride and liver sodium, potassium, and calcium levels were found to be
      significantly decreased.

PMID- 17180418
TI  - Determination of impact of urbanization on agricultural land and wetland land use
      in Balcovas' delta by remote sensing and GIS technique.
AB  - Because of their intense vegetation and the fact that they include areas of
      coastline, deltas situated in the vicinity of big cities are areas of greet
      attraction for people who wish to get away from in a crowded city. However,
      deltas, with their fertile soil and unique flora and fauna, need to be protected.
      In order for the use of such areas to be planned in a sustainable way by local
      authorities, there is a need for detailed data about these regions. In this
      study, the changes in land use of the Balcova Delta, which is to the immediate
      west of Turkey's third largest city Izmir, from 1957 up to the present day, were
      investigated. In the study, using aerial photographs taken in 1957, 1976 and 1995
      and an IKONOS satellite image from the year 2005, the natural and cultural
      characteristics of the region and changes in the coastline were determined
      spatially. Through this study, which aimed to reveal the characteristics of the
      areas of land already lost as well as the types of land use in the Balcova delta
      and to determine geographically the remaining areas in need of protection, local
      authorities were provided with the required data support. Balcova consists of
      flat and fertile wetland with mainly citrus-fruit orchards and flower-producing
      green houses. The marsh and lagoon system situated in the coastal areas of the
      delta provides a habitat for wild life, in particular birds. In the Balcova
      Delta, which provides feeding and resting for migratory birds, freshwater sources
      are of vital importance for fauna and flora. The settlement area, which in 1957
      was 182 ha, increased 11-fold up to the year 2005 when it reached 2,141 ha. On
      the other hand, great losses were determined in farming land, olive groves,
      forest and in the marsh and lagoon system. This unsystematic and rapid
      urbanization occurring in the study region is not only causing the loss of
      important agricultural land and wetland, but also lasting water and soil
      pollution.

PMID- 17180419
TI  - Optimized coagulation of high alkalinity, low temperature and particle water: pH
      adjustment and polyelectrolytes as coagulant aids.
AB  - The Yellow River in winter as source water is characterized as high alkalinity,
      low temperature and low particle concentrations, which have brought many
      difficulties to water treatment plants. This study fully examines the optimized
      coagulation process of the Yellow River by conventional and pre-polymerized metal
      coagulants, pH adjustment and polyelectrolytes as the primary coagulants or
      coagulant aids. For all the metal coagulants, polyaluminum chlorides are superior
      to traditional metal coagulants due to their stable polymeric species and low
      consumption of alkalinity. The removal of natural organic matter by monomeric
      metal coagulants can be improved through pH adjustment, which is in accordance
      with the higher concentration of polymeric species formed at corresponding pH
      value. With the addition of polyelectrolytes as coagulant aids, the coagulation
      performance is significantly improved. The effective removal of dissolved organic
      matter is consistent with high charge density, while molecular weight is
      relatively important for removing particles, which is consistent with
      polyelectrolytes as primary coagulants. These results suggest that the
      coagulation mechanisms in the removal of dissolved organic matter and particles
      are different, which may be exploited for optimized coagulation for the typical
      source water in practice.

PMID- 17180420
TI  - Tsunami survey expedition: preliminary investigation of Maldivian coral reefs two
      weeks after the event.
AB  - On December 26th 2004, a earthquake west of Sumatra generated a devastating
      tsunami. Hundreds of thousands of people fell victim. Economic losses were
      greatest in those countries dependant on tourism. The impact in the Maldives on
      persons and things was modest. Immediately following the event and
      notwithstanding the lack of scientific data, the mass media gave catastrophic
      reports on the state of coral reefs in the area. This paper reports on the first
      survey on coral reefs in the Maldives after the Tsunami. Ocean walls, passes,
      inner reefs, and shoals in the North and South Male atolls, were surveyed two
      weeks after the event. Significant damage was recorded in the passes in the South
      Male atoll. Our observations showed that the damage was more or less extensive
      depending on latitude and topography. Sri Lanka may have broken the wave's rush,
      reducing the extent of the impact on northern atolls. The water's acceleration
      inside the passes was so intense as to cause reef collapses. The observed damage
      represents a minimum fraction of the entire coral reef system. Tourist perception
      of the area seems unchanged. These data may be used to disseminate correct
      information about the state of Maldives coral reefs, which would be useful in
      relaunching local economy.

PMID- 17180421
TI  - Assessment of the health impacts of particulates from the redevelopment of Kings
      Cross.
AB  - The Kings Cross/St. Pancras area has been a rail transport hub from Central
      London to the Midlands and North Eastern England since the middle of the
      nineteenth century and dust from the Kings Cross railway lands was even described
      by Charles Dickens. The Channel Tunnel high speed Rail Link (CTRL) is being
      constructed between 2001 and 2007 to connect continental Europe to Central
      London. The CTRL and associated development will help regenerate an area that is
      surrounded by deprived high density housing estates. London Borough of Camden has
      set up an extensive particulate monitoring programme to determine if there are
      any health impacts on local residents from emissions from the demolition and
      construction work. This article assesses the results from particulate
      measurements in 2003-2004 and compares this to baseline conditions before the
      redevelopment work began. The evidence suggests that although 2003 had higher
      than average pollution levels in the UK as a whole, even higher levels of
      particulates in the size range PM(10)-PM(2.5) (defined as PM(coarse)) were
      measured in Kings Cross. Due to the size of these particulates, they tend to be
      released from construction works rather than transport or secondary particulate
      sources. Concentrations in 2004 were lower than 2003, but this was primarily due
      to meteorological conditions. The paper also looks at the health of the local
      population and discusses whether these elevated levels are creating a problem and
      legally constitute a statutory nuisance. The Council continues to work with the
      contractors to try and ensure best practical means to minimise dust emissions and
      their effect on local residents.

PMID- 17180422
TI  - Evaluation of bulk deposition in protected woodland area in western Poland.
AB  - Research on precipitation carried out systematically at the University station at
      Jeziory in the Wielkopolski National Park (western Poland) allowed the
      determination of pollutants deposited with precipitation in this forest
      ecosystem. During 13 years of study, the pH of precipitation was found to persist
      at a low level (4.33 on average), which resulted a substantial deposition of
      H(+). Values of acidifying and basic ions deposited in this area were determined
      and compared with the respective figures obtained at selected EMEP stations
      studying background pollution, the means for Poland, and areas subjected to
      considerable human impact. The use of the critical load function made it possible
      to establish that the S and N deposition for 2002-2005 were below its line.

PMID- 17180423
TI  - Identification of residues of sulfosulfuron and its metabolites in subsoil
      dissipation kinetics and factors influencing the stability and degradation of
      residues from topsoil to subsoil under predominant cropping conditions.
AB  - Long term stability of sulfosulfuron was investigated in subsoil under the
      natural wheat cropping conditions. Experiments were conducted by applying a
      commercial formulation of sulfosulfuron on soil at 50 g/ha and 100 g/ha. To
      understand the factors influencing the persistence of residues two different
      experiments were conducted. In one experiment wheat crop was cultivated once at
      the beginning of the two years study period and subsequently the plots were kept
      undisturbed for the remaining period. In another experiment cultivation of
      subsequent crops were continued during the study period. In both the cases
      sulfosulfuron was applied only once at the beginning of the study. Representative
      soil samples were collected from the depths viz., 0-5, 15, 30, 45, 60 and 90 cm
      on different pre determined sampling occasions 50, 100, 200, 300, 400, 500 and
      600 days after the application of the herbicide. The collected soil samples were
      analyzed for the residues of sulfosulfuron. Under the influence of continuous
      cropping conditions residues of sulfosulfuron were found to be relatively low
      when compared with the soil samples collected from the agriculture plots
      maintained without any cultivation. The residues detected are in the range 0.001
      to 0.017 microg/g. Samples collected from the depth, at 30 to 45 cm showed higher
      residual concentrations. Soil samples were also showed the presence of break down
      products. The data has been confirmed by LC-MS/MS. The relation between residue
      content of sulfosulfuron and the factors contributing the stability of herbicide
      concentration were also studied.

PMID- 17180424
TI  - Pattern classification and recognition of invertebrate functional groups using
      self-organizing neural networks.
AB  - Self-organizing neural networks can be used to mimic non-linear systems. The main
      objective of this study is to make pattern classification and recognition on
      sampling information using two self-organizing neural network models.
      Invertebrate functional groups sampled in the irrigated rice field were
      classified and recognized using one-dimensional self-organizing map and self
      organizing competitive learning neural networks. Comparisons between neural
      network models, distance (similarity) measures, and number of neurons were
      conducted. The results showed that self-organizing map and self-organizing
      competitive learning neural network models were effective in pattern
      classification and recognition of sampling information. Overall the performance
      of one-dimensional self-organizing map neural network was better than self
      organizing competitive learning neural network. The number of neurons could
      determine the number of classes in the classification. Different neural network
      models with various distance (similarity) measures yielded similar
      classifications. Some differences, dependent upon the specific network structure,
      would be found. The pattern of an unrecognized functional group was recognized
      with the self-organizing neural network. A relative consistent classification
      indicated that the following invertebrate functional groups, terrestrial blood
      sucker; terrestrial flyer; tourist (nonpredatory species with no known functional
      role other than as prey in ecosystem); gall former; collector (gather, deposit
      feeder); predator and parasitoid; leaf miner; idiobiont (acarine ectoparasitoid),
      were classified into the same group, and the following invertebrate functional
      groups, external plant feeder; terrestrial crawler, walker, jumper or hunter;
      neustonic (water surface) swimmer (semi-aquatic), were classified into another
      group. It was concluded that reliable conclusions could be drawn from comparisons
      of different neural network models that use different distance (similarity)
      measures. Results with the larger consistency will be more reliable.

PMID- 17180425
TI  - Transport and adhesion of Escherichia coli JM109 in soil aquifer treatment (SAT):
      one-dimensional column study.
AB  - Bacteria transport and adhesion experiments under water-saturated and partially
      saturated conditions were examined over a wide range of ionic strength, from 1 to
      100 mM KCl, CaCl(2), and MgCl(2), and at water contents of 0.15 and 0.22 in sand
      columns packed with three different sands, baked, sterilized, and raw sands in
      order to investigate the effects of ionic strength, water content, and porous
      media type on the microbial adhesion in soil aquifer treatment (SAT). Well
      characterized Escherichia coli JM109 were used as model bacterial cells in this
      study. Column study results showed that bacterial deposition rates increased with
      increasing ionic strength and decreasing water content, and were higher in raw
      sand columns than those in other sand columns. The Derjaguin-Landau-Verwey
      Overbeek (DLVO) theory was applied to experimental results in order to consider
      the interaction energies between the bacterial cells and collector grains;
      results revealed that a considerable amount of bacterial cells was weakly
      deposited onto the solid surfaces in secondary minimum.

PMID- 17180426
TI  - A new method for determination of chlorophylls in freshwater algae.
AB  - A new method (NMM, using acetic acid fiber filter and 90% ethanol) was
      established to determine chlorophyll in freshwater algae, and it was compared
      with US standard method (USM, using glass fiber filter and 90% acetone) and the
      method recommend by EPA of China (CHM, using acetic acid fiber filter and 90%
      acetone). The precision and repeatability of NMM is equivalent to that of USM,
      but NMM is safer to laboratory workers than USM and CHM because ethanol was used
      as solvent in NMM instead of acetone used in USM and CHM, and time and money were
      also greatly saved by the new method. The precision and repeatability of CHM was
      much less than USM and NMM, and the advice improving the method was proposed that
      the extraction time must be prolonged.

PMID- 17180427
TI  - Early responses to acute ozone exposure in two Fagus sylvatica clones differing
      in xeromorphic adaptations: photosynthetic and stomatal processes, membrane and
      epicuticular characteristics.
AB  - Two Fagus sylvatica L. clones were used to investigate the early responses to
      acute O3 exposure (150 nL L(-1), i.e., 1.35x ambient hourly peak in rural Italy)
      and whether xeromorphic adaptations affect gas exchange, membrane, and
      epicuticular responses. One clone originated in a wet and temperate climate in
      Central Italy (Tuscany); the other clone originated in a warmer and drier climate
      in the southern-most part of the F. sylvatica distribution (Sicily). Because of
      higher base gas exchange rates, the most negative effects of O3 exposure (gas
      exchange impairment, uncoupling between net photosynthesis and stomatal
      conductance, increased membrane lipid peroxidation) were found in the southern
      clone. Xeromorphic adaptations (higher epicuticular waxes and stomatal density,
      lower leaf wettability and size) were found in this clone. Our results suggest
      that xeromorphism may increase O3 sensitivity in species not adapted to face
      water stress, like the mesophilic F. sylvatica, when experiments are carried out
      with full irrigation. We present evidence describing the relationship between gas
      exchange and number and status of stomata. Stomatal density and the structural
      damage to stomata resulting from O3 exposure did not affect gas exchange: In
      fact, non-stomatal limitations to photosynthesis prevailed over stomatal
      limitations.

PMID- 17180428
TI  - Are nitrogen-fertilized forest soils sinks or sources of carbon?
AB  - We developed a simple conceptual model that tracks nitrogen and carbon jointly
      through an N fertilized forest ecosystem. The stimulation of growth increases the
      litterfall and imports substrate for soil microorganisms. Microbial biomass forms
      according to the supply of C and N. The formation of microbial biomass is
      accompanied by respiratory C losses. The quantity of CO2 efflux depends on the C
      use efficiency of microbes. When excess N is available, the microbial activity is
      accelerated and the demand for substrate is high. Litterfall supplies an
      insufficient amount of C to the soil. In such a case, labile soil C is
      mineralized and the net effect of N fertilization is a loss of soil C. A strong N
      fertilization effect on the aboveground biomass can offset the soil C loss. In
      the case of a low N dosage or high N losses due to leaching or emission of
      nitrogen oxides, the soil C loss is small. The conceptual model was applied to a
      case study. The field data, collected over a time span of several decades, could
      not support sound conclusions on the temporal trend of soil C because the spatial
      and temporal variability of the chemical data was high. The conceptual model
      allowed to give an evaluation of the fertilization effect on soil C based on
      reproducible principles.

PMID- 17180429
TI  - Effects of acid rock drainage on stocked rainbow trout (Oncorhynchus mykiss): an
      in-situ, caged fish experiment.
AB  - In-situ caged rainbow trout (Oncorhynchus mykiss) studies reveal significant fish
      toxicity and fish stress in a river impacted by headwater acid rock drainage
      (ARD). Stocked trout survival and aqueous water chemistry were monitored for 10
      days at 3 study sites in the Snake River watershed, Colorado, U.S.A. Trout
      mortality was positively correlated with concentrations of metals calculated to
      be approaching or exceeding conservative toxicity thresholds (Zn, Mn, Cu, Cd).
      Significant metal accumulation on the gills of fish stocked at ARD impacted study
      sites support an association between elevated metals and fish mortality.
      Observations of feeding behavior and significant differences in fish relative
      weights between study site and feeding treatment indicate feeding and metals
      related fish stress. Together, these results demonstrate the utility of in-situ
      exposure studies for stream stakeholders in quantifying the relative role of
      aqueous contaminant exposures in limiting stocked fish survival.

PMID- 17180430
TI  - Spatial and temporal variations of eutrophication in Western Chaohu Lake, China.
AB  - Chaohu Lake is one of the five largest fresh lakes in China. Now it is one of the
      three most eutrophic lakes of China attracting more and more attention in the
      world-wide-concern. From Zhongmiao Temple to Qitouzui Cape, the lake is divided
      into two parts. The eutrophication state of the lake western part is more serious
      than that of the eastern part, mainly because the former is the final place of
      industrial and municipal wastewater from Hefei City, the capital of Anhui
      Province. Through six routine national sampling sites of the Western Chaohu Lake,
      we analyzed the yearly variation of eutrophication from 1984 to 2004, the monthly
      variation from 2001 to 2004 and the spatial distribution and variation of the six
      sampling sites in the year 1992, 1996, 2000 and 2004 with Trophic State Index
      (TSI). The main reasons for Chaohu Lake eutrophication and the spatial and
      temporal variations of eutrophication in Western Chaohu Lake were discussed.

PMID- 17180432
TI  - Geostatistical analysis of spatial and temporal variations of groundwater level.
AB  - Groundwater and water resources management plays a key role in conserving the
      sustainable conditions in arid and semi-arid regions. Applying management tools
      which can reveal the critical and hot conditions seems necessary due to some
      limitations such as labor and funding. In this study, spatial and temporal
      analysis of monthly groundwater level fluctuations of 39 piezometric wells
      monitored during 12 years was carried out. Geostatistics which has been
      introduced as a management and decision tool by many researchers has been applied
      to reveal the spatial and temporal structure of groundwater level fluctuation.
      Results showed that a strong spatial and temporal structure existed for
      groundwater level fluctuations due to very low nugget effects. Spatial analysis
      showed a strong structure of groundwater level drop across the study area and
      temporal analysis showed that groundwater level fluctuations have temporal
      structure. On average, the range of variograms for spatial and temporal analysis
      was about 9.7 km and 7.2 months, respectively. Ordinary and universal kriging
      methods with cross-validation were applied to assess the accuracy of the chosen
      variograms in estimation of the groundwater level drop and groundwater level
      fluctuations for spatial and temporal scales, respectively. Results of ordinary
      and universal krigings revealed that groundwater level drop and groundwater level
      fluctuations were underestimated by 3% and 6% for spatial and temporal analysis,
      respectively, which are very low and acceptable errors and support the
      unbiasedness hypothesis of kriging. Although, our results demonstrated that
      spatial structure was a little bit stronger than temporal structure, however,
      estimation of groundwater level drop and groundwater level fluctuations could be
      performed with low uncertainty in both space and time scales. Moreover, the
      results showed that kriging is a beneficial and capable tool for detecting those
      critical regions where need more attentions for sustainable use of groundwater.
      Regions in which were detected as critical areas need to be much more managed for
      using the current water resources efficiently. Conducting water harvesting
      systems especially in critical and hot areas in order to recharge the
      groundwater, and altering the current cropping pattern to another one that need
      less water requirement and applying modern irrigation techniques are highly
      recommended; otherwise, it is most likely that in a few years no more crop would
      be cultivated.

PMID- 17180431
TI  - Pesticide residues in bovine milk from a predominantly agricultural state of
      Haryana, India.
AB  - One hundred forty seven samples of bovine milk were collected from 14 districts
      of Haryana, India during December 1998-February 1999 and analysed for the
      presence of organochlorine pesticide (OCPs) residues. summation operator HCH,
      summation operator DDT, summation operator endosulfan and aldrin were detected in
      100%, 97%, 43% and 12% samples and with mean values of 0.0292, 0.0367, 0.0022 and
      0.0036 microg/ml, respectively. Eight percent samples exceeded the maximum
      residue limit (MRL) of 0.10 mg/kg as recommended by WHO for summation operator
      HCH, 4% samples of 0.05 mg/kg for alpha-HCH, 5% samples of 0.01 mg/kg for gamma
      HCH, 26% samples of 0.02 mg/kg for beta-HCH as recommended by PFAA and 24%
      samples of 0.05 mg/kg as recommended by FAO for summation operator DDT.
      Concentrations of beta-HCH and p,p'-DDE were more as compared to other isomers
      and metabolites of HCH and DDT.

PMID- 17180434
TI  - Assessment of seasonal enrichment of heavy metals in respirable suspended
      particulate matter of a sub-urban Indian city.
AB  - Heavy metals in respirable suspended particulate matter (RSPM) were analyzed for
      different seasons, from July 2002 to December 2002, at different locations in
      Hisar (Haryana, India). The samples were analyzed for Pb, As, Ni, Cu, Mn, Fe and
      Mg on atomic absorption spectrophotometer (AAS) in air-acetylene flame. The
      concentration of heavy metals was more in the studied residential area followed
      by industrial area and commercial area. The concentrations of Fe, As, Ni and Mn
      were found to be more compared to other metals. Further, the concentrations of
      all the heavy metals were higher in pre-monsoon (extended summer) and monsoon
      followed by post-monsoon, autumn and winter. Meteorology played an important role
      in concentration of heavy metals in RSPM. Turbulent conditions resulted in higher
      concentration owing to re-suspension and external input whereas, low wind speed,
      low temperature and high relative humidity favoured low concentration of the
      pollutants. The evaluation of enrichment factor revealed that Pb, As, Ni, Cu, and
      Mn are emitted, chiefly from anthropogenic sources and Fe and Mg are associated
      with natural sources.

PMID- 17180433
TI  - Contaminants-induced oxidative damage on the carp Cyprinus carpio collected from
      the upper Yellow River, China.
AB  - The Yellow River, the second largest river in China, is the most important
      resource of water supply in North China. In the last 40 years, even in the upper
      Yellow River, with the development of industry and agriculture, more and more
      contaminants have been discharged into this river and greatly polluted the water.
      Although a routine chemical component analysis has been performed, little is
      known about the real toxic effects of the polluted water on organisms at
      environmental level. To explore whether the pollutants induced oxidative stress
      and damage to aquatic organisms, malondialdehyde (MDA) level and activities of
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and
      glutathione S-transferase (GST) in hepatopancreas, kidney and intestine of the
      field-collected carp Cyprinus carpio from a mixed polluted (Lanzhou Region, LZR)
      and a relatively unpolluted (Liujiaxia Region, LJXR) sites of the upper Yellow
      River were measured. The results showed that when the values of LZR compared with
      those of LJXR, SOD and GST activities increased and GPx activity decreased
      significantly in all the three organs (P < 0.05-0.01); CAT activity decreased but
      MDA level increased significantly (P < 0.05-0.01) only in kidney and intestine.
      In conclusion, the results of this study suggest that the pollutants can induce
      obvious oxidative damage in the carp, and the SOD, GST and GPx might be better
      indicators for the oxidative damage in aquatic organisms.

PMID- 17180435
TI  - Forest vegetation monitoring and foliar chemistry of red spruce and red maple at
      Acadia National Park in Maine.
AB  - The USDA Forest Service Forest Health Monitoring (FHM) program indicators,
      including forest mensuration, crown condition classification, and damage and
      mortality indicators were used in the Cadillac Brook and Hadlock Brook watershed
      forests at Acadia National Park (ANP) along coastal Maine. Cadillac Brook
      watershed burned in a wildfire in 1947. Hadlock Brook watershed, undisturbed for
      several centuries, serves as the reference site. These two small watersheds have
      been gauged and monitored at ANP since 1998 as part of the Park Research and
      Intensive Monitoring of Ecosystems Network (PRIMENet). Forest vegetation at
      Hadlock Brook was dominated by late successional species such as Acer saccharum,
      Fagus grandifolia, Betula alleghaniensis, Acer rubrum and Picea rubens. Forest
      vegetation at Cadillac Brook, on the other hand, was younger and more diverse and
      included those species found in Hadlock as well as early successional species
      such as Betula papyrifera and Populus grandidentata. Differences in forest
      species composition and stand structure were attributed to the severe wildfire
      that affected the Cadillac Brook watershed. Overall, the forests at these ANP
      watersheds were healthy with a low percentage (</=22%) of trees showing symptoms
      of damage.Foliar nitrogen (N) concentrations were higher in A. rubrum and P.
      rubens trees growing in Hadlock Brook watershed, but differences were significant
      only for P. rubens. Foliar aluminum (Al) concentrations were also higher in both
      species growing in Hadlock Brook watershed but differences were significant only
      for A. rubrum. Foliar calcium (Ca) and manganese (Mn) concentrations, on the
      other hand, were significantly lower in Hadlock Brook watershed for both species.
      Foliar potassium (K) was significantly higher for P. rubens growing in Hadlock
      Brook. No differences in foliar concentrations of magnesium (Mg), phosphorus (P),
      boron (B), copper (Cu) and lead (Pb) were found between watersheds. The higher
      foliar N concentrations as well as higher foliar concentrations of Ca and Al
      might indicate early stages of N saturation and acidification in Hadlock Brook
      watershed as also suggested by Hadlock Brook stream N flux data in published
      PRIMENet studies at ANP.

PMID- 17180436
TI  - Watershed nitrogen and mercury geochemical fluxes integrate landscape factors in
      long-term research watersheds at Acadia National Park, Maine, USA.
AB  - This paper is an overview of this special issue devoted to watershed research in
      Acadia National Park (Acadia NP). The papers address components of an integrated
      research program on two upland watersheds at Acadia NP, USA (44 degrees 20' N
      latitude; 68 degrees 15' E longitude). These watersheds were instrumented in 1998
      to provide a long-term foundation for regional ecological and watershed research.
      The research was initiated as part of EPA/NPS PRIMENet (Park Research and
      Intensive Monitoring of Ecosystems Network), a system of UV-monitoring stations
      and long-term watershed research sites located in US national parks. The initial
      goals at Acadia NP were to address research questions about mercury, acid rain,
      and nitrogen saturation developed from prior research. The project design was
      based on natural differences in forests and soils induced by an intense wildfire
      in one watershed in 1947. There is no evidence of fire in the reference watershed
      for several hundred years. We are testing hypotheses about controls on surface
      water chemistry, and bioavailability of contaminants in the contrasting
      watersheds. The unburned 47-ha Hadlock Brook watershed is 70% spruce-fir mature
      conifer forest. In contrast, burned 32-ha Cadillac Brook watershed, 4 km
      northeast of the Hadlock watershed, is 20% regenerating mixed northern hardwoods
      and 60% shrub/rocky balds. Differences in atmospheric deposition are controlled
      primarily by forest stand composition and age. The watersheds are gauged and have
      water chemistry stations at 122 m (Cadillac) and 137 m (Hadlock); watershed
      maximum elevations are 468 and 380 m, respectively. The stream water chemistry
      patterns reflect, in part, the legacy of the intense fire, which, in turn,
      controls differences in forest vegetation and soil characteristics. These factors
      result in higher nitrogen and mercury flux from the unburned watershed,
      reflecting differences in atmospheric deposition, contrasting ecosystem pools of
      nitrogen and mercury, and inferred differences in internal cycling and
      bioavailabilty.

PMID- 17180438
TI  - The origin of an unusual sex chromosome constitution in Acomys sp. (Rodentia,
      Muridae) from Tanzania.
AB  - This paper describes a case which presents an evident variation from the
      "standard" XX/XY sex chromosomal constitution in a rodent, Acomys sp. This
      species known to be found in three localities of East Africa has only recently
      been separated from A. spinosissimus, its closest relative. In our study, five
      specimens of Acomys sp. and eight specimens of A. spinosissimus were live-trapped
      in five localities. Comparisons between the two taxa assed by G-banding show a
      complete homology in the chromosomal shape and banding pattern for 29 pairs of
      chromosomes corresponding to the complete autosomal set of A. spinosissimus.
      However, while all the A. spinosissimus analysed have 2n = 60 and a XY-XX system,
      in Acomys sp. males and females constitute mosaics for sex chromosomes in the
      bone marrow cells. Females (2n = 59, 60) have an excess (97%) of aneuploid cells
      with one single giant X chromosome, and males (2n = 60, 61) show X0/XY cells
      occurring in somatic tissues and XY cells in the germinal lineage. In addition,
      an odd heterochromatic submetacentric chromosome was identified in all the cells
      examined in two males and a female of Acomys sp. Since this chromosome was not
      related to sex determination and it is not present in all the analysed specimens,
      it can be considered as a B chromosome. Finally, the in situ fluorescence
      hybridisation (FISH) with telomeric probes showed a very intense interstitial
      telomeric signal (ITS) at the medial part on the long heterochromatic arm of the
      X chromosome. This could be due to recent chromosomal rearrangement.

PMID- 17180437
TI  - Bioreclamation of coalmine overburden dumps--with special empasis on
      micronutrients and heavy metals accumulation in tree species.
AB  - Major environmental impacts of opencast mining are degradation of landscape and
      aesthetics of the area by creating huge overburden dumps and deep voids at the
      mining sites. These overburden dumps are characterised by high rock fragment
      contents, low moisture retention capacity, higher bulk density, low nutrients,
      lower pH and elevated metal concentrations. Overburden dumps are reclaimed by
      tree species for stabilising as well as pollution control and overall improvement
      of the visual aesthetics. A field study was carried out in the old reclaimed coal
      mine overburden dumps at KD Heslong project, Central Coalfields, India to study
      the physico-chemical changes in the reclaimed overburden dumps and determines the
      magnitude of trace elements accumulation in the planted tree species. Total,
      bioavailable and acid extractable trace metals concentration in minesoils of
      overburden dump and topsoil in the mining areas was compared with undisturbed
      soil. The study showed that tree plantation improves the moisture contents, bulk
      density, pH and overall nutrient contents of minesoils. The study revealed that
      lower pH in the minesoils increases the bioavailabity of metals but concentration
      were found within toxic limits. However, ratio between total and bioavailable
      metals was found lower in overburden dumps than topsoil due to low pH and lack of
      organic matter. Out of six tree species studied, Bambusa shows highest
      accumulation of Fe and Cr. Bioaccumulation coefficient for Cr and Zn was found 74
      times in Bambusa and 83 times in Dalbergia sissoo. The results of the study
      underscore the need for close monitoring of trace elements in reclaimed
      overburden dumps. Tree species like Dalbergia sissoo, Eucalyptus, Cassia seamea,
      Acaccia mangium and Peltaphorum were found to be the best species for
      bioreclamation of overburden dumps.

PMID- 17180439
TI  - Isolation and characterization of salmonid telomeric and centromeric satellite
      DNA sequences.
AB  - Satellite DNA clones with a 37 bp repeat unit were obtained from BglII-digested
      genomic DNA of Masu salmon (Oncorhynchus masou) and Chum salmon (O. keta).
      Fluorescence in situ hybridization (FISH) analysis with the isolated clones as a
      probe showed that these repetitive sequences were localized in the telomeric
      regions of chromosomes in both species. Southern and dot blot analyses suggested
      conservation of homologous sequences with similar repeat unit in other salmonids
      including the species of the genus Oncorhynchus and Salvelinus, but lack or
      scarcity of such sequences in the genus Hucho and Salmo. Similarly, polymerase
      chain reaction (PCR)-based cloning of satellite DNA referring to a reported
      Rainbow trout (O. mykiss) centromeric sequence was successful for the
      Oncorhynchus, Salvelinus and Hucho species. The obtained satellite DNA clones
      were localized with FISH in the centromeric regions of chromosomes of the species
      from these three genera. Although PCR cloning of the centromeric satellite DNA
      had failed in the Salmo species due to some base changes in the priming sites,
      dot blot hybridization analysis suggested conservation of homologous satellite
      DNA in the genus Salmo as in the other three genera. In the neighbor-joining tree
      of cloned centromeric satellite DNA sequences, the genus Oncorhynchus and
      Salvelinus formed adjacent clades, and the clade of the genus Hucho included the
      reported centromeric sequence of the genus Salmo. Conservation pattern and
      molecular phylogeny of the telomeric and centromeric satellite DNA sequences
      isolated herein support a close phylogenetic relationship between the genus
      Oncorhynchus and Salvelinus and between the Salmo and Hucho.

PMID- 17180441
TI  - Extensive balanitis xerotica obliterans (BXO) involving the anterior urethra and
      scrotum.
AB  - We describe an unusual case of balanitis xerotica obliterans (BXO) involving the
      entire anterior urethra and the scrotum that had presented as a palpable nodular
      scrotal mass with obstructive voiding symptoms in middle aged man. He was managed
      by a staged urethroplasty. We report the first such case of BXO involving the
      scrotum resulting in a nodular mass that has not been described and reported till
      date.

PMID- 17180440
TI  - Microvessel density and regulators of angiogenesis in malignant and nonmalignant
      prostate tissue.
AB  - The aim of this study was to investigate the relationship between microvessel
      density (MVD), positive and negative angiogenic factors, and established
      prognostic factors in prostate cancer (PC), and, to clarify the effect of
      angiogenic factors to angiogenesis. The vascularization of neoplastic, non
      neoplastic prostate tissue was determined by CD34 immunostaining. Angiogenetic
      mediators VEGF, bFGF, TSP-1, and p53 were studied by immunohistochemistry.
      Neovascularization and p53, VEGF, and TSP-1 expressions of tumorous tissue were
      higher than non-tumorous tissue. The bFGF expression in these tissues was not
      different. The p53 expression was not correlated with the expressions of VEGF,
      bFGF, and TSP-1 in PC. Our results demonstrate a significant increase in MVD,
      VEGF, TSP-1, and p53 expressions in prostate tumorigenesis. The pretreatment sPSA
      was the only parameter demonstrating significant correlation with tumor grade and
      may have a value in the prediction of aggressive tumor behavior in PC.

PMID- 17180442
TI  - Unexpected complication after cystometry in the hypocompliant urinary bladder:
      formation of a knot in the double lumen urethral catheter--a case report.
AB  - Urodynamic evaluation is frequently used in the follow-up of the treatment and
      diagnosis of incontinence, which develops in connection with a neurogenic or non
      neurogenic reason. There is no identified serious complication during or after
      urodynamic evaluation, present in the literature up to date. Hematuria, due to
      the urethral catheter, the development of oedema in the urinary bladder wall and
      the development of urinary bladder spasm as a result of catheter irritation, are
      some of the complications, which may occur. In this paper, twist and knot
      formation in the double lumen urethral catheter after cystometry of a patient
      with a hypocompliant urinary bladder, has been presented.

PMID- 17180443
TI  - Localization and expression of selenoprotein S in the testis of Psammomys obesus.
AB  - Selenium is an essential trace element and selenoprotein S is a member of the
      selenoprotein family that has the non-standard amino acid selenocysteine
      incorporated into the polypeptide. Dietary selenium has been shown to play an
      important protective role in a number of diseases including cancer, immune
      function and the male reproductive system. In this study, we have observed high
      levels of selenoprotein S gene expression in the testis from Psammomys obesus.
      Real-time PCR and immunofluorescence demonstrate that selenoprotein S expression
      is low in testes from 4-week-old animals but increases significantly by 8 weeks
      of age and remains high until 17 weeks of age. Selenoprotein S protein is
      detected in primary spermatocytes, Leydig and Sertoli cells of 8, 12 and 17-week
      old animals. These results suggest that selenoprotein S may play a role in
      spermatogenesis.

PMID- 17180445
TI  - NMR assignment of the leucine-rich repeat domain of LANP/Anp32a.

PMID- 17180444
TI  - Fine-tuning of protein domain boundary by minimizing potential coiled coil
      regions.
AB  - Structural determination of individual protein domains isolated from multidomain
      proteins is a common approach in the post-genomic era. Novel and thus
      uncharacterized domains liberated from intact proteins often self-associate due
      to incorrectly defined domain boundaries. Self-association results in missing
      signals, poor signal dispersion and a low signal-to-noise ratio in (1)H-(15)N
      HSQC spectra. We have found that a putative, non-canonical coiled coil region
      close to a domain boundary can cause transient hydrophobic self-association and
      monomer-dimer equilibrium in solution. Here we propose a rational method to
      predict putative coiled coil regions adjacent to the globular core domain using
      the program COILS. Except for the amino acid sequence, no preexisting knowledge
      concerning the domain is required. A small number of mutant proteins with a
      minimized coiled coil region have been rationally designed and tested. The
      engineered domains exhibit decreased self-association as assessed by (1)H-(15)N
      HSQC spectra with improved peak dispersion and sharper cross peaks. Two
      successful examples of isolating novel N-terminal domains from AAA-ATPases are
      demonstrated. Our method is useful for the experimental determination of domain
      boundaries suited for structural genomics studies.

PMID- 17180446
TI  - On using oscillating time-dependent restraints in MD simulation.
AB  - The use of time-dependent restraints in molecular simulation in order to generate
      a conformational ensemble for molecules that is in accordance with measured
      ensemble averages for particular observable quantities is investigated. Using a
      model system consisting of liquid butane and the cyclic peptide antamanide the
      reproduction of particular average (3) J-coupling constant values in a molecular
      dynamics simulation is analysed. It is shown that the multiple-valuedness and the
      sizeable gradients of the Karplus curve relating (3) J-coupling constants
      measured in NMR experiments to the corresponding torsional-angle values cause
      severe problems when trying to restrain a (3) J-coupling constant to a value
      close to the extrema of the Karplus curve. The introduction of a factor
      oscillating with time into the restraining penalty function alleviates this
      problem and enhances the restrained conformational sampling.

PMID- 17180447
TI  - Human glomerular mesangial IP15 cell line as a suitable model for in vitro
      cadmium cytotoxicity studies.
AB  - Cadmium represents a major environmental pollutant that may induce severe damage,
      especially in the kidney where cadmium accumulates. While cadmium is known to
      severely impair renal tubular functions, glomerular structures are also potential
      targets. Owing to their contractile properties, glomerular mesangial cells play a
      major role in the control of glomerular hemodynamics and influence the
      ultrafiltration coefficient. Cell cultures provide alternative and fruitful
      models for study of in vitro toxicology. However, the use of primary human
      mesangial cell cultures is hampered by their limited survival span and their
      rapid dedifferentiation during passages. This study presents a human stable
      immortalized mesangial cell line, designated IP15. Cell characteristics were
      investigated by the detection of known mesangial markers, as well as their
      ability to contract in response to angiotensin II. IP15 cells were used to
      investigate cadmium uptake and morphological changes such as cell contraction and
      cytoskeleton protein expression. The IC(50) cytotoxicity index was obtained with
      3.55 micromol/L using neutral red assay for 24 h. After cadmium exposure (1
      micromol/L, determined as nonlethal concentration), 0.38 microg Cd/mg protein was
      internalized by the cells as evaluated by inductively coupled plasma optical
      emission spectrometry (ICP/OES). Cadmium induced a significant cell surface
      reduction that correlated with smooth-muscle alpha-actin disorganization. Thus,
      the IP15 cell line is a suitable model for study of in vitro cadmium cytotoxicity
      in mesangial cells and allows sufficient material to be obtained for future
      studies of the intracellular effects of cadmium exposure.

PMID- 17180448
TI  - Measurement of carbonic anhydrase isozyme VI (CA-VI) in bovine sera, saliva, milk
      and tissues.
AB  - Concentrations of bovine carbonic anhydrase isozyme VI (CA-IV) in bovine serum,
      saliva, normal milk, colostrum, submandibular gland, liver, and mammary gland
      were determined. CA-VI was purified from bovine saliva and an antibody to CA-VI
      was generated. The concentrations of CA-VI in the saliva (7.8 +/- 7.9 microg/ml),
      serum (2.1+/- 5.7 ng/ml), milk (7.9 +/- 12.1 ng/ml), submandibular gland (284.7
      microg/g protein), liver (921.0 +/- 180.7 ng/g protein) and mammary gland (399.6
      +/- 191.2 ng/g protein) were determined by ELISA. No seasonal change in CA-VI
      levels was observed in normal milk. The concentration of CA-VI in colostrum (day
      1 post partum) was 119 ng/ml and decreased rapidly by 1 month following birth.
      Mammary gland contained much smaller amounts than the submandibular gland. CA-VI
      mRNA was detected in the liver and mammary gland of cow by RT-PCR. The ELISA used
      in this study proved to be a precise and sensitive method for determining CA-VI
      concentrations in saliva, serum, milk and tissue specimens from cows. The ELISA
      may enable the study of changes in CA-VI associated with hereditary or metabolic
      disorders of the salivary gland, mammary gland and liver using small samples of
      saliva, serum or milk.

PMID- 17180449
TI  - Prevalence, molecular characterization and antimicrobial resistance of
      thermophilic campylobacter isolates from cattle, hens, broilers and broiler meat
      in south-eastern Italy.
AB  - Eleven cattle farms, 8 layer farms, 7 broiler farms and 30 broiler meat samples
      were investigated in south-eastern Italy throughout 2003 to evaluate the
      prevalence, the molecular type and antimicrobial resistance of thermophilic
      Campylobacters. A total of 398 samples were analysed. One Campylobacter isolate
      for each positive faecal swab and three isolates per positive broiler meat sample
      were selected for further analysis. Multiplex PCR was performed for species-level
      identification and PCR-RFLP of the flagellin A gene for genotyping. Resistance to
      14 antimicrobials was studied in 188 Campylobacter isolates. Prevalence of
      campylobacters was high both on farms (100%) and in food samples (73%). On 4/11
      cattle farms and on 10/15 poultry farms more than one species was isolated. The
      presence of more than one genotype was found on 8/11 cattle farms, on 10/15
      poultry farms and in 8/22 Campylobacter-positive food samples. High rates of
      resistance to quinolone were observed: 9/31 (29%) C. jejuni bovine isolates, 4/22
      (18%) C. jejuni poultry isolates, and 14/26 (54%) C. coli poultry isolates.
      Resistance to sulphamethoxazole-trimethoprim was also observed frequently: 18/26
      (69%) of the avian C. coli strains, 25/31 (80%) of the C. jejuni strains isolated
      from poultry and 15/22 (68%) of those isolated from cattle were resistant. There
      was a significant difference between the rate of resistance to macrolides of C.
      coli and C. jejuni isolated in poultry, which amounted to 23% and 3%,
      respectively. This study provided data on the prevalence and antimicrobial
      resistance of thermophilic campylobacters in south-eastern Italy and confirmed
      that flaA-typing is an efficient tool to study the epidemiology of Campylobacter
      strains in short-term investigations.

PMID- 17180450
TI  - Validation of a commercially available human immunoturbidimetric assay for
      haptoglobin determination in canine serum samples.
AB  - Haptoglobin is a positive acute-phase protein with a valuable role as a marker of
      inflammation in both human and veterinary medicine. The aim of this study was to
      validate a commercially available immunoturbidimetric method designed for human
      haptoglobin determination (Izasa SA, Barcelona, Spain) for its use in canine
      samples. Cross-reactivity between anti-human haptoglobin antiserum and canine
      haptoglobin was found when agarose gel immunodiffusion and ELISA tests were
      performed. The use of canine pooled serum with haptoglobin concentration of 6.3
      g/L as standard provided higher analytical range than commercially available
      standards. Intra-assay and inter-assay coefficients of variation were 2.49% and
      4.60%, respectively. A linear regression model between immunoturbidimetric
      results and a previously validated spectrophotometric method (Tridelta
      Development Limited, Ireland) yielded a slope at 95% confidence interval of 0.94
      (0.86, 1.02) and y-intercept at 95% confidence interval of 0.11 (-0.59, 0.82). No
      significant differences were produced by anticoagulants, lipaemia and
      bilirubinaemia, although haemolysis significantly decreased haptoglobin. A
      significant increase of haptoglobin concentration was detected in inflammatory
      conditions such as pyometra and leishmaniasis, in neoplastic conditions, and
      after glucocorticoid administration. Canine serum haptoglobin concentration can
      be reliably measured using the commercially available Izasa immunoturbidimetric
      method developed for human haptoglobin determination. This method is precise and
      accurate, provides a wider analytical range than previous reported methods, and
      can be easily automated and used for routine haptoglobin determination in canine
      samples.

PMID- 17180452
TI  - Polymerase chain reaction (PCR) amplification of IS6110 sequences to detect
      Mycobacterium tuberculosis complex from formalin-fixed paraffin-embedded tissues
      of deer (Axis axis).

PMID- 17180451
TI  - Segment-dependent expression of muscarinic acetylcholine receptors and G-protein
      coupling in the equine respiratory tract.
AB  - Muscarinic receptors are considered to be of comparable clinical importance in
      chronic obstructive pulmonary disease (COPD) in equines and in humans. At
      present, data are scarce on the expression and distribution of probable subtypes
      of these receptors and their signalling pathways in airway segments, including
      lung parenchyma and bronchial and tracheal epithelium with the underlying smooth
      muscle in horses. Specific [N-methyl-3H]scopolamine chloride ([3H]NMS) binding to
      all three tissues was saturable and of high affinity, with KD values ranging
      between 1.6+/-0.7 and 1.9+/-0.3 nmol/L. [3H]NMS binding identified a higher
      density of total muscarinic receptors (fmol/mg protein) in the trachea (720+/-59
      nmol/L) than in bronchi (438+/-48 nmol/L) or lung (22 +/- 3 nmol/L). Competitive
      binding studies using [3H]NMS and the unlabelled subtype-selective antagonists
      pirenzepine and telenzepine (M1), methoctramine and himbacine (M2), 4
      diphenylacetoxy-N-methylpiperidine (4-DAMP) (M3), tropicamide (M4) and mamba
      toxin (MT-3) (M4) indicated the presence of at least three muscarinic receptor
      subtypes in peripheral lung tissue (50:40:24-28%: M2>M3>M1), whereas in bronchus
      and trachea M2 subtypes (87-90%) predominated over M3 (14-22%), and M1 subtypes
      were lacking. No differences were found between tissues in high-affinity binding
      sites for carbachol in the absence (31-36%) or presence of guanosine 5'
      triphosphate (GTP) (approximately 100%). Western blotting for G-protein alpha
      subunits showed a much more robust expression of G(alphai1/2) in the trachea
      (with highest receptor density) than in the lung or bronchi, whereas G(alphas)
      protein was dominantly expressed in bronchus. Concomitantly, carbachol inhibited
      isoproterenol- and GTP-stimulated adenylyl cyclase activity with increasing
      muscarinic receptor expression (trachea > bronchi > lung). We conclude that the
      expression and signalling pathways of muscarinic receptors in the equine
      respiratory tract are segment-dependent. These receptors might contribute to the
      pathogenesis of COPD in the horse and could provide potential drug targets for
      the therapeutic use of anticholinergics in this species.

PMID- 17180453
TI  - Analysis of cerebrospinal fluid from clinically healthy Iranian fat-tailed sheep.

PMID- 17180454
TI  - Effects of long-term cyanide ingestion by pigs.
AB  - Animal performance and health status are adversely affected by long-term cyanide
      ingestion; however, the effects of cyanide ingestion by pigs have not been fully
      determined. The aim of the present study was to determine the effects of
      prolonged exposure to different doses of potassium cyanide (KCN) in growing
      finishing swine. Twenty-four pigs, 45 days of age, were divided into four equal
      groups and treated with different doses of KCN: 0, 2.0, 4.0 or 6.0 mg per kg body
      weight per day for 70 consecutive days. The results showed a significant
      alteration in thiocyanate, creatinine and urea levels and in alanine
      aminotransferase activity of swine dosed with 4.0 and 6.0 mg/kg/KCN. Thyroid
      weight was significantly increased in those pigs from 4.0 mg/kg KCN group, but no
      change in cholesterol, triiodothyronine or thyroline levels were observed. Body
      and carcase weights, body weight gain, and bacon thickness were not affected by
      KCN treatment. The histopathological study revealed increased numbers of vacuoles
      in the colloid of thyroid follicles, degeneration of cerebellar white matter and
      Purkinje cells, degeneration of renal tubular epithelial cells, caryolysis and
      pyknosis in hepatocytes, and disturbance of the normal lobular architecture of
      the liver in all treated pigs. Thus, long-term administration of KCN to swine
      affects several tissues and could adversely affect animal production.

PMID- 17180455
TI  - Serum sialic acid levels in calves with pneumonia.

PMID- 17180457
TI  - Empathizing and systemizing in adults with and without autism spectrum
      conditions: cross-cultural stability.
AB  - This study tests the empathizing-systemizing (E-S) theory of sex differences and
      the extreme male brain (EMB) theory of autism. Three groups of participants took
      part: n = 48 people with autism spectrum, n = 137 general population controls,
      and n = 1,250 university student controls. Each participant completed the Empathy
      Quotient (EQ) and the Systemizing Quotient (SQ). RESULTS: The autism spectrum
      condition (ASC) group scored significantly lower than controls on the EQ, and
      significantly higher on the SQ. Among both control groups, females scored
      significantly higher than males on the EQ, whilst males scored significantly
      higher than females on the SQ. The distribution of 'brain types', based on the
      difference between EQ and SQ scores, showed distinct profiles for people with
      ASC, control males and control females.

PMID- 17180456
TI  - Distinct roles for the 5' and 3' untranslated regions in the degradation and
      accumulation of chloroplast tufA mRNA: identification of an early intermediate in
      the in vivo degradation pathway.
AB  - Elongation factor Tu in Chlamydomonas reinhardtii is a chloroplast-encoded gene
      (tufA) whose 1.7-kb mRNA has a relatively short half-life. In the presence of
      chloramphenicol (CAP), which freezes translating chloroplast ribosomes, a 1.5-kb
      tufA RNA becomes prominent. Rifampicin-chase analysis indicates that the 1.5-kb
      RNA is a degradation intermediate, and mapping studies show that it is missing
      176-180 nucleotides from the 5' end of tufA. The 5' terminus of the intermediate
      maps to a section of the untranslated region (UTR) predicted to be highly
      structured and to encode a small ORF. The intermediate could be detected in older
      cultures in the absence of CAP, indicating that it is not an artifact of drug
      treatment. Also, it did not overaccumulate in the chloroplast ribosome-deficient
      mutant, ac20 cr1, indicating its stabilization is specific to elongation-arrested
      ribosomes. To determine if the 5' UTR of tufA is destabilizing, the corresponding
      region of the atpA-aadA-rbcL gene was replaced with the tufA sequence, and
      introduced into the chloroplast genome; the 3' UTR was also substituted for
      comparison. Analysis of these transformants showed that the transcripts
      containing the tufA 3'-UTR accumulate to significantly lower levels. Data from
      constructs based on the vital reporter, Renilla luciferase, confirmed the
      importance of the tufA 3'-UTR in determining RNA levels, and suggested that the
      5' UTR of tufA affects translation efficiency. These data indicate that the in
      vivo degradation of tufA mRNA begins in the 5' UTR, and is promoted by
      translation. The data also suggest, however, that the level of the mature RNA is
      determined more by the 3' UTR than the 5' UTR.

PMID- 17180458
TI  - Development of a video-based evaluation tool in Rett syndrome.
AB  - This paper describes the development of a video-based evaluation tool for use in
      Rett syndrome (RTT). Components include a parent-report checklist, and video
      filming and coding protocols that contain items on eating, drinking,
      communication, hand function and movements, personal care and mobility. Ninety
      seven of the 169 families who initially agreed to participate returned a
      videotape within 8 months of the first request. Subjects whose videos were
      returned had a similar age profile to those who did not provide a video but were
      more likely to have classical than atypical RTT. Evidence of the content and
      social validity and inter-rater reliability on 11 videos is provided. Video may
      provide detailed, objective assessment of function and behaviour in RTT.

PMID- 17180459
TI  - The Autism Diagnostic Observation Schedule: revised algorithms for improved
      diagnostic validity.
AB  - Autism Diagnostic Observation Schedule (ADOS) Modules 1-3 item and domain total
      distributions were reviewed for 1,630 assessments of children aged 14 months to
      16 years with an autism spectrum disorder (ASD) or with heterogeneous non
      spectrum disorders. Children were divided by language level and age to yield more
      homogeneous cells. Items were chosen that best differentiated between diagnoses
      and were arranged into domains on the basis of multi-factor item-response
      analysis. Reflecting recent research, the revised algorithm now consists of two
      new domains, Social Affect and Restricted, Repetitive Behaviors (RRB), combined
      to one score to which thresholds are applied, resulting in generally improved
      predictive value.

PMID- 17180461
TI  - Emotion perception in Asperger's syndrome and high-functioning autism: the
      importance of diagnostic criteria and cue intensity.
AB  - This study compared emotion perception accuracy between children with Asperger's
      syndrome (AS) and high-functioning autism (HFA). Thirty children were diagnosed
      with AS or HFA based on empirically supported diagnostic criteria and
      administered an emotion perception test consisting of facial expressions and tone
      of voice cues that varied in intensity. Participants with AS and the typically
      developing standardization sample of the emotion perception instrument had the
      same mean emotion perception accuracy, whereas participants with HFA performed
      significantly worse. Results also provided preliminary evidence for a difference
      in accuracy perceiving low-intensity tone of voice cues between participants with
      HFA and AS. Future research to build on these initial findings should include
      attention to tone of voice, underlying processing, and cue intensity.

PMID- 17180460
TI  - Communicative competence in parents of children with autism and parents of
      children with specific language impairment.
AB  - While the primary language deficit in autism has been thought to be pragmatic,
      and in specific language impairment (SLI) structural, recent research suggests
      phenomenological and possibly genetic overlap between the two syndromes. To
      compare communicative competence in parents of children with autism, SLI, and
      down syndrome (DS), we used a modified pragmatic rating scale (PRS-M). Videotapes
      of conversational interviews with 47 autism, 47 SLI, and 21 DS parents were
      scored blind to group membership. Autism and SLI parents had significantly lower
      communication abilities than DS parents. Fifteen percent of the autism and SLI
      parents showed severe deficits. Our results suggest that impaired communication
      is part of the broader autism phenotype and a broader SLI phenotype, especially
      among male family members.

PMID- 17180463
TI  - Multivariate objective response detectors (MORD): statistical tools for
      multichannel EEG analysis during rhythmic stimulation.
AB  - The presence of cerebral evoked responses can be tested by using objective
      response detectors. They are statistical tests that provide a threshold above
      which responses can be assumed to have occurred. The detection power depends on
      the signal-to-noise ratio (SNR) of the response and the amount of data available.
      However, the correlation within the background noise could also affect the power
      of such detectors. For a fixed SNR, the detection can only be improved at the
      expense of using a longer stretch of signal. This can constitute a limitation,
      for instance, in monitored surgeries. Alternatively, multivariate objective
      response detection (MORD) could be used. This work applies two MORD techniques
      (multiple coherence and multiple component synchrony measure) to EEG data
      collected during intermittent photic stimulation. They were evaluated throughout
      Monte Carlo simulations, which also allowed verifying that correlation in the
      background reduces the detection rate. Considering the N EEG derivations as close
      as possible to the primary visual cortex, if N = 4, 6 or 8, multiple coherence
      leads to a statistically significant higher detection rate in comparison with
      multiple component synchrony measure. With the former, the best performance was
      obtained with six signals (O1, O2, T5, T6, P3 and P4).

PMID- 17180462
TI  - Iron acquisition by Legionella pneumophila.
AB  - For nearly 20 years, it was believed that Legionella pneumophila does not produce
      siderophores. Yet, we have now determined that L. pneumophila secretes a
      siderophore (legiobactin) that is detectable by the CAS assay. We have optimized
      conditions for legiobactin expression, shown its biological activity, and found
      genes (lbtAB) involved in its production and secretion. LbtA is homologous with
      siderophore synthetases from E. coli (aerobactin), Sinorhizobium (rhizobactin),
      and Bordetella (alcaligin), while LbtB is a member of the major facilitator
      superfamily of multidrug efflux pumps. Mutants lacking lbtAB produce 40-70% less
      CAS reactivity. The lbtA mutant is also defective for growth in deferrated media
      containing citrate, indicating that legiobactin is required in conditions of
      severe iron limitation. lbtAB mutants grow normally in macrophages and amoebae
      host cells as well as within the lungs of mice. L. pneumophila does express lbtA
      in macrophages, suggesting that legiobactin has a dispensable role in infection.
      Legiobactin is iron repressed and does not react in the Csaky and Arnow assays.
      Anion-exchange HPLC has been used to purify legiobactin, and thus far, structural
      analysis suggests that the molecule is similar but not identical to rhizobactin,
      rhizoferrin, and alcaligin. The residual CAS reactivity present in supernatants
      of the lbtAB mutants suggests that L. pneumophila might produce a second
      siderophore. Besides siderophores, we have determined that ferrous iron
      transport, encoded by feoB, is critical for L. pneumophila growth in low-iron
      conditions, in host cells, and in the mammalian lung. Some of our other studies
      have discovered a critical, yet undefined, role for the L. pneumophila cytochrome
      c maturation locus in low-iron growth, intracellular infection, and virulence.

PMID- 17180464
TI  - Implementation issues in approximate methods for stochastic Hodgkin-Huxley
      models.

PMID- 17180465
TI  - Physiologic pulsatile flow bioreactor conditioning of poly(ethylene glycol)-based
      tissue engineered vascular grafts.
AB  - Mechanical conditioning represents a potential means to enhance the biochemical
      and biomechanical properties of tissue engineered vascular grafts (TEVGs). A
      pulsatile flow bioreactor was developed to allow shear and pulsatile stimulation
      of TEVGs. Physiological 120 mmHg/80 mmHg peak-to-trough pressure waveforms can be
      produced at both fetal and adult heart rates. Flow rates of 2 mL/sec,
      representative of flow through small diameter blood vessels, can be generated,
      resulting in a mean wall shear stress of approximately 6 dynes/cm(2) within the 3
      mm ID constructs. When combined with non-thrombogenic poly(ethylene glycol) (PEG)
      based hydrogels, which have tunable mechanical properties and tailorable
      biofunctionality, the bioreactor represents a flexible platform for exploring the
      impact of controlled biochemical and biomechanical stimuli on vascular graft
      cells. In the present study, the utility of this combined approach for improving
      TEVG outcome was investigated by encapsulating 10T-1/2 mouse smooth muscle
      progenitor cells within PEG-based hydrogels containing an adhesive ligand (RGDS)
      and a collagenase degradable sequence (LGPA). Constructs subjected to 7 weeks of
      biomechanical conditioning had significantly higher collagen levels and improved
      moduli relative to those grown under static conditions.

PMID- 17180466
TI  - Primary coloduodenal fistula in Crohn's disease.
AB  - The posterior surface of the proximal transverse colon and the anterior surface
      of the descending duodenum are intimately related, predisposing to fistulization
      in this area. We herein describe a rare case of benign duodenocolic fistula
      secondary to Crohn's disease. We emphasize the clinical presentation with
      fecaloid vomiting, as well as the establishment of the diagnosis by endoscopy,
      which are both extremely rare. The presence of a colonic stricture supports the
      hypothesis that the disease started in the colon rather than in the duodenum, and
      mandates surgical rather than medical therapy. Our case illustrates the
      possibility of coloduodenal fistula in patients with long-standing Crohn's
      disease, which should be considered in patients presenting with fecaloid
      vomiting, abdominal pain, and weight loss.

PMID- 17180467
TI  - The interaction between polycationic poly-lysine dendrimers and charged and
      neutral fluorescent probes.
AB  - The interactions between polycationic poly-lysine dendrimers and hydrophobic
      fluorescent probes (anionic ANS and neutral Prodan) were studied. R121 and R131
      dendrimers were not able to interact with anionic and neutral hydrophobic groups.
      R124 was able to interact with neutral and anionic hydrophobic fluorescent
      probes, however mainly through hydrophobic forces. Dendrimers R155 and R169
      showed the maximal effects. The strongest interactions observed for R169 can be
      explained by intramolecular folding (stacking) of its two L-proline residues.
      Using double fluorescence titration technique for ANS probe allowed to receive
      such constant of binding and the number of binding centers: for R121, 1.8 x 10(3)
      (mol/l)(-1) and 1.07; for R124, 12.1 x 10(3) (mol/l)(-1) and 0.48; for R131, 4.7
      x 10(3) (mol/l)(-1) and 0.48; for R155, 9.2 x 10(3) (mol/l)(-1) and 1.36; for
      R169, 39.6 x 10(3) (mol/l)(-1) and 0.97. Thus, neutral and anionic hydrophobic
      probes can be used for the fast preliminary screening of binding properties of
      newly synthesized polycationic dendrimers.

PMID- 17180468
TI  - A cross-linguistic speech error investigation of functional complexity.
AB  - This work is a systematic, cross-linguistic examination of speech errors in
      English, Hindi, Japanese, Spanish and Turkish. It first describes a methodology
      for the generation of parallel corpora of error data, then uses these data to
      examine three general hypotheses about the relationship between language
      structure and the speech production system. All of the following hypotheses were
      supported by the data. Languages are equally complex. No overall differences were
      found in the numbers of errors made by speakers of the five languages in the
      study. Languages are processed in similar ways. English-based generalizations
      about language production were tested to see to what extent they would hold true
      across languages. It was found that, to a large degree, languages follow similar
      patterns. However, the relative numbers of phonological anticipations and
      perseverations in other languages did not follow the English pattern. Languages
      differ in that speech errors tend to cluster around loci of complexity within
      each language. Languages such as Turkish and Spanish, which have more
      inflectional morphology, exhibit more errors involving inflected forms, while
      languages such as Japanese, with rich systems of closed-class forms, tend to have
      more errors involving closed-class items.

PMID- 17180471
TI  - Invited commentary on animal models in psychiatry: animal models of non
      conventional human behavior.
AB  - Conventional behavior, of which linguistic behavior is the principal variety, is
      identified as responses having formal properties that are not determined by the
      natural properties of stimulus objects, but instead by properties attributed to
      those objects under the auspices of particular groups. Given the ubiquity of this
      type of behavior in the repertoires of human beings and its complete absence in
      those of non-humans, the argument is made that animal models of human disorders,
      in which disturbances of conventional behaviors constitute defining features, are
      not sufficiently analogous to these conditions in humans to be pursued with good
      result. Because conventional behavior of the linguistic type is ubiquitous in the
      repertoires of normally developed human adults, it is suggested that the behavior
      of pre-verbal infants and/or non-verbal persons is preferable to that of adults
      as the phenomenal source for the construction of animal models of human
      psychological events. The observation and measurement of psychological events is
      held to be complicated by a number of their characteristics, including their
      complexity by virtue of whole organism participation, their essential
      complementarily with stimulus events, and the corrigibility of both form and
      function over their repeated occurrences, among others. The implications of these
      features for modeling enterprises are discussed.

PMID- 17180469
TI  - Insights on blastomere nuclearity.
AB  - PURPOSE: To analyze the results of our transferred embryos, especially those that
      "changed" their blastomere nuclearity from Multinucleated (MN) to Mono-nucleated
      during development. METHODS: Pregnancies where at least one MN embryo was
      transferred were retrospectively evaluated and categorized in order to record and
      follow-up on the ones that were implanted. Embryos were classified as normal
      (when all blastomeres were mono-nucleated on day one and two of development),
      corrected (multinucleated embryos on day one that became mono-nucleated on day
      two) and non-corrected (multinucleated either on day one, on day two or both
      days). RESULTS: There were 633 transfer cycles analyzed. Thirty-three percent
      (206) had at least one embryo with a MN blastomere at a given stage of
      development. Pregnancy and implantation rates were 29.0% and 19.0% for the group
      of exclusively mono-nucleated embryo transfers, and 28.6% and 15.8% for the group
      with at least one MN embryo transferred. The pregnancy outcome for "corrected"
      and "non-corrected" embryos could be corroborated unequivocally in only 9 cases,
      with an outcome of 8 and 4 normal babies, respectively. CONCLUSIONS: Because the
      amount of data analyzed is not satisfactorily large, differences were not
      significantly different; however, a trend may exist showing that normal at term
      pregnancies obtained from corrected embryos are more likely to occur than those
      from non-corrected embryos. Nuclear observation on a daily basis should be one of
      the strategies used to select the best embryos for transferring, to improve
      implantation rates and avoid multiple pregnancies.

PMID- 17180470
TI  - Potent systemic antitumor immunity induced by vaccination with chemotactic
      prostate tumor associated antigen gene-modified tumor cell and blockade of B7-H1.
AB  - We previously reported that several DNA fragments from human prostate-specific
      membrane antigen (hPSM), mouse prostatic acid phosphatase (mPAP), and human
      prostate-specific antigen (hPSA) genes were selected and fused to create a novel
      hPSM-mPAP-hPSA fusion gene (named 3P gene), and human secondary lymphoid tissue
      chemokine (SLC), 3P, and human IgG Fc genes were inserted into pcDNA3.1 to
      construct a DNA vaccine, designated pSLC-3P-Fc. In this report, to establish a
      more efficient treatment for immunotherapy against prostate cancer, the construct
      was transfected into B16F10 to generate gene-modified tumor cell vaccine (named
      B16F10-SLC-3P-Fc). In poorly immunogenic B16F10 mouse melanoma model, the
      immunization with B16F10-SLC-3P-Fc resulted in a strong antitumor response and
      50% of tumor-bearing mice achieved long-term survival (>120 days). In vivo
      depletion of lymphocytes indicated that CD8(+) T cells were involved in the
      direct tumor killing, whereas CD4(+) T lymphocytes were required for the
      induction of CD8(+) CTL response in B16F10-SLC-3P-Fc-immunized mice. Splenocytes
      from B16F10-SLC-3P-Fc-immunized mice specifically recognized and lysed PSM, PAP,
      PSA, and 3P expressing tumor cells. The combined therapy of B16F10-SLC-3P-Fc plus
      anti-B7-H1 MAbs further enhanced the immune response. Rechallenge experiment
      showed that a persistent memory response was successfully induced by the combined
      therapy. These observations suggest pSLC-3P-Fc-modified tumor cells could serve
      as a vaccine against prostate cancer, and the therapy combined with anti-B7-H1
      MAbs further enhanced the antitumor immune response.

PMID- 17180472
TI  - Invasive early-onset neonatal group B streptococcal cases--Alaska, 2000-2004.
AB  - OBJECTIVE: We conducted a review of invasive early-onset neonatal group B
      Streptococcus (GBS) infections that occurred during 2000-2004 in Alaska to
      determine the proportion of cases that might have been prevented by complete
      implementation of the 2002 Centers for Disease Control and Prevention (CDC)
      guidelines. METHODS: Cases were identified from statewide laboratory-based
      surveillance conducted by the CDC Arctic Investigations Program, and from the
      Alaska Medicaid database using International Classification of Diseases 9 codes
      038.0, 041.02, 320.2, and 482.3. Neonates were considered to have early-onset
      disease if clinical illness within 6 days after birth was accompanied by GBS
      isolation from a normally sterile site. Maternal and neonatal medical records
      were reviewed. Potentially preventable cases were those for whom the 2002 CDC GBS
      maternal screening and intrapartum antimicrobial prophylaxis (IAP) guidelines
      were not completely implemented. Preventability of events not related to
      clinician implementation of the guidelines were not considered. RESULTS: Twenty
      one neonates with invasive early-onset GBS disease were identified (0.42/1,000
      live births). Three of the eight mothers for whom IAP was indicated, did not
      receive adequate IAP. Nine of the 13 mothers for whom there was no indication for
      IAP, had not been screened appropriately. Therefore, a total of 12 neonates were
      determined to have had potentially preventable GBS disease. CONCLUSIONS: Over 50%
      of the invasive early-onset neonatal GBS cases in Alaska were potentially
      preventable. The majority of these cases may have been prevented by closer
      adherence to either specific IAP administration guidelines or to maternal
      screening guidelines.

PMID- 17180473
TI  - An innovative, effective and cost effective survey method using a survey-check
      response format.
AB  - Maximizing the response rate to surveys involves thoughtful choices about survey
      design, sampling and collection methods. This paper describes an innovative
      survey method, to provide immediate reinforcement for responding and to minimize
      the response cost. This method involves using a questionnaire printed as checks
      on security (anti-fraud) paper with questions and responses separated using a
      perforated tear off section. Once a participant completes the survey, the
      response area is detached from the questions, thus protecting the confidentiality
      of the subject, and the check is returned via the banking system. This report
      describes the survey-check methodology, the survey flow process, and the results
      from four research studies which have used this method. These studies include (1)
      a technology accessibility survey of parents with children enrolled in a low
      income preschool program; (2) a parent report of their child's behavior used as
      screening criteria for inclusion in a computer-mediated parent education project;
      (3) a follow-up questionnaire as part of a longitudinal study of child behavior,
      covering home and classroom interventions, and service utilization, and; (4) a
      survey of dentists in support of efforts to recruit them to participate in a
      randomized control trial of tobacco cessation in dental offices. The results of
      using this method show great improvement in response rates over traditionally
      administered surveys for three of the four reported studies. Results are
      discussed in terms of future applications of this method, limitations, and
      potential cost savings.

PMID- 17180474
TI  - Breast cancer local recurrence: risk factors and prognostic relevance of early
      time to recurrence.
AB  - BACKGROUND: Local recurrence occurs in 10%-20% of patients treated with breast
      conserving surgery for stage I-II breast cancer. The aim of the present study was
      to investigate breast cancer local recurrence, potential risk factors, and
      prognostic impact. METHODS: A total of 503 patients treated with breast
      conserving surgery were included in the study. All patients underwent axillary
      dissection and postoperative radiotherapy, and all patients had negative margins
      at pathological examination. Median follow-up was 82 months. Local recurrence was
      classified as early when it occurred within 2 years from surgery. The risk
      factors for local recurrence and overall survival were estimated by univariate
      and multivariate analyses. RESULTS: Forty-six cases (9.1%) of local recurrence
      were observed, 11 of which occurred within 24 months of surgery; the other 35,
      sometime later. Statistically significant risk factors for local recurrence were
      premenopausal status, peritumoral vascular invasion, multifocality, and absence
      of estrogen receptors. Independent negative prognostic factors for overall
      survival at 5 and 10 years were N stage, absence of estrogen receptors, and early
      time to recurrence. Overall survival at 10 years was 10.0% for patients with
      early recurrence, 87.5% for patients with late recurrence, and 87.9% for patients
      without recurrence. CONCLUSIONS: None of the studied clinicopathological
      characteristics alone is a determinant for the choice of surgical treatment.
      Younger patients treated with breast-conserving surgery should receive aggressive
      postsurgical treatment and should be followed with an intensive follow-up program
      when metastatic axillary lymph nodes, negative estrogen receptors, or peritumoral
      vascular invasion are present.

PMID- 17180476
TI  - Parameter predicting the recurrence of adhesive small bowel obstruction in
      patients managed with a long tube.
AB  - INTRODUCTION: Some of our patients showed a recurrence of adhesive small bowel
      obstruction (ASBO) with nonoperative management. The aim of this study was to
      evaluate the parameters predicting the recurrence of ASBO in patients managed
      with a long tube. METHODS: Of 234 patients with ASBO admitted from April 1998 to
      September 2002, a total of 91 who recovered with nonoperative management after
      long tube placement were enrolled in this retrospective clinical study. We
      divided them into two groups for follow-up: the recurrence group and the no
      recurrence group. We compared baseline characteristics, the number of previous
      ASBO admissions, the number of abdominal operations, the interval from the onset
      of symptoms to long-tube insertion, the duration of long-tube placement, the type
      of the contrasted intestine through the long tube, the location of the long-tube
      tip, and the drainage volume through the long tube between the two groups. We
      then examined the cumulative recurrence rate. RESULTS: A significant difference
      was found in the number of previous ASBO admissions, the duration of long-tube
      placement (77 hours vs. 43 hours), the contrasted intestine through the long
      tube, and the location of the long-tube tip. By multivariate analysis, the
      duration of long-tube placement was an independent parameter predicting the
      recurrence of ASBO. CONCLUSIONS: These results suggest that the duration of long
      tube placement might serve as a parameter for predicting recurrence of ASBO in
      patients managed with a long tube.

PMID- 17180475
TI  - Iatrogenic vascular injuries in varicose vein surgery: a systematic review.
AB  - BACKGROUND: Iatrogenic vascular injuries during varicose vein surgery are
      serious. The aim of this study was to investigate their nature and consequences.
      METHOD: A systematic literature research was performed. RESULTS: The incidence is
      low (0.0017%-0.3%). We found 81 patients suffering from 87 vascular injuries-44
      arterial and 43 deep vein injuries. CONCLUSION: Vascular injuries during varicose
      surgery are rare but serious. They are avoidable, and when they occur, early
      recognition is crucial. Bleeding is a common symptom, especially in deep venous
      injury. In our study, we reviewed the literature on 81 patients with 87 vascular
      injuries. Laceration or division of the femoral vein dominated venous injuries
      (28/43). Partial stripping of the femoral vein was not common (4/43) and occurred
      when the strip probe passed into the deep veins through a perforator. Arterial
      stripping predominated in arterial injuries (17/44) and happened when stripping
      distally during a primary operation, as reported by experienced surgeons, in
      nonobese women. Major arterial complications resulted in ischemia, often with
      diagnostic delay and poor reconstruction results. Only 30% (13/44) of arterial
      injuries were detected peroperatively. The amputation rate was 34% (15/44), but
      rose to 100% if combined with intra-arterial sclerotherapy (5/5 cases). When
      stripping an artery below the femoral artery, the amputation rate was high (42%;
      5/12) and morbidity severe (85%; 11/12). All fatal injuries (5 cases) were
      venous. Anatomic knowledge and awareness of the possibility of vascular
      complications should be preventive. Early detection by routine checking of
      arterial circulation is important.

PMID- 17180477
TI  - Impact of tumor spread to the cystic duct on the prognosis of patients with
      gallbladder carcinoma.
AB  - INTRODUCTION: The importance of gallbladder carcinoma spread to the cystic duct
      has not yet been described. Although the cystic duct is contiguous with the
      gallbladder, it is located in the hepatoduodenal ligament and differs in
      structure from the gallbladder. The incidence and prognostic significance of
      cancer spread to the cystic duct in patients with gallbladder cancer is unclear.
      METHODS: Surgical specimens from 42 patients who underwent resection for advanced
      gallbladder carcinoma were examined retrospectively. RESULTS: Altogether, 13
      (31%) of the patients had cancer spread to the cystic duct. The incidences of
      perineural invasion, lymph node metastasis, and venous invasion were
      significantly higher in these patients than in the other 29 patients without
      cancer spread to the cystic duct (P = 0.027, 0.034, and 0.034, respectively). The
      3- and 5-year survival rates of these 13 patients were significantly lower than
      those of the other 29 patients (15.4% vs. 51.0% and 7.7% vs. 46.6%, respectively,
      P < 0.0001 each). Multivariate analysis using the Cox proportional hazard model
      identified positive cancer spread to the cystic duct and depth of invasion
      (beyond serosa) as significant independent indicators of a poor prognosis.
      CONCLUSIONS: Cancer spread to the cystic duct is an indicator of poor prognosis
      in patients with gallbladder carcinoma. This may be due to the high incidence of
      concomitant perineural invasion and lymph node metastasis associated with cancer
      spread.

PMID- 17180478
TI  - Impact of patient- and disease-specific factors on SLNB in breast cancer
      patients. Are current guidelines justified?
AB  - BACKGROUND: The evidence on which to base guidelines for sentinel lymph node
      biopsy (SLNB) in breast cancer is still limited. In order to facilitate the
      further implementation of renewed guidelines, we evaluated patient- and disease
      specific factors for their impact on the results of SLNB. MATERIALS AND METHODS:
      Prospective data acquisition from patients undergoing surgery for primary
      invasive breast cancer was performed. All patients underwent SLNB using the
      radiocolloid or the combined technique. The association of patient- and disease
      specific factors to detection rate and false-negative rate was calculated using
      univariate and multivariate analyses (P < 0.05 considered as significant).
      Calculation of the false-negative rate was based on patients who underwent a
      backup axillary dissection. RESULTS: Among 455 consecutively enrolled patients, a
      significant inverse association to the detection rate was found for extracapsular
      extension of non-SLN metastases, body mass index (BMI), number of involved lymph
      nodes, pT category, tumor size, and age. A significant association to the false
      negative rate to identify macrometastases was found for pT category, tumor size,
      and grading. Other factors, such as prior surgery, multicentric tumor growth, or
      vascular invasion, showed no influence. A cut-point analysis revealed that a
      tumor size of 2 cm separated the collective of patients with the highest
      significance in regard to the false-negative rate (9% vs. 25%). CONCLUSION: Our
      results indicate that SLNB can be safely used in elderly and obese patients with
      multicentric tumors and those having undergone prior surgery for benign breast
      disease. However, the method should be applied with caution in patients with
      tumors larger than 2 cm.

PMID- 17180479
TI  - Computer-assisted operative planning in adult living donor liver transplantation:
      a new way to resolve the dilemma of the middle hepatic vein.
AB  - An adequate venous outflow is essential for securing viability of both graft and
      remnant in adult living donor liver transplantation (ALDLT). Seventy-five
      potential live liver donors were evaluated for LDLT by means of an "all-in-one"
      CT, which defined the biliary tree, portal vein, hepatic artery, and hepatic vein
      anatomy. The acquired data sets were further analysed by means of the software
      HepaVision (MeVis, Germany). Only a minority (29%) of potential donors were found
      to have a vascular and biliary anatomy consistent with the classically described
      "normal" patterns. The vast majority (71%) had "anatomical variations". Thirty
      nine (52%) donors underwent ALDLT hepatectomy. The right hepatic vein was
      dominant in 64 cases, representing 48 +/- 6% of the total liver volume (TLV). The
      middle hepatic vein was dominant in 11 cases, making up 40 +/- 8% of the TLV. The
      left hepatic vein was never dominant. The volume contribution of the middle
      hepatic vein (MHV) was 114-782 ml for the right and 87-419 ml for the left
      hemiliver. Computer-assisted planning allows for the 3D reconstruction of the
      vascular and biliary anatomy, automatic calculation of the total and territorial
      liver volumes, and risk analysis of hepatic vein dominance relationships. This
      comprehensive data acquisition supports preoperative evaluation and provides a
      high degree of safety for donors and improved outcomes for recipients.

PMID- 17180481
TI  - Pro: SLNB in DCIS.

PMID- 17180480
TI  - Primary hyperaldosteronism secondary to unilateral adrenal hyperplasia: an
      unusual cause of surgically correctable hypertension. A review of 30 cases.
AB  - INTRODUCTION: Unilateral adrenal hyperplasia (UAH) is a rare, surgically
      correctable cause of primary hyperaldosteronism (PH). We report 2 cases and
      review the literature for cases of PH secondary to UAH successfully treated via
      surgery. METHODS: Two cases of UAH treated at our institution were
      retrospectively reviewed. In addition, we reviewed 28 cases of UAH previously
      reported in the English literature. RESULTS: Median patient age was 49 (range: 10
      62) years, with a male to female ratio of 1.7:1. All patients were hypertensive,
      with a median preoperative systolic and diastolic blood pressure of 170 (range:
      135-250) mmHg and 110 (range: 75-140) mmHg, respectively. Most patients were
      hypokalemic, with a median serum potassium level of 2.8 (range: 1.4-3.9) mmol/l.
      Ten out of 13 patients (77%) who underwent postural studies had a decrease or no
      change in the plasma aldosterone level, suggesting a unilateral source of
      hyperaldosteronism, and 9/17 patients (53%) who underwent a computed tomography
      (CT) scan were correctly localized. Twelve patients underwent adrenal
      scintigraphy with or without dexamethasone suppression, of whom 6 (50%) were
      correctly localized. In 1 patient, adrenal scintigraphy demonstrated localization
      to the opposite gland. Adrenal venous sampling (AVS) was performed in 22 patients
      and successfully localized the lesion in all the patients. At a median follow-up
      of 12 (range: 3-96) months postsurgery, 47% of patients (14/30) were completely
      cured of their hypertension and 50% (15/30) had improved control. All 30 patients
      were cured of hypokalemia. CONCLUSION: Although the existence of UAH remains
      controversial, it is increasingly accepted as a unique pathologic entity and has
      an excellent outcome after unilateral adrenalectomy.

PMID- 17180482
TI  - Assessment of in vivo effects of the prestige fuel oil spill on the mediterranean
      mussel immune system.
AB  - A laboratory experiment was carried out to study immune function alteration of
      the mussel Mytilus galloprovincialis when exposed to the Prestige oil spilled in
      November 2002 on the northwestern Spanish coast. Mussels were maintained for 4
      months in tanks with flowing seawater and with 1, 2, and 0 kg (controls) Prestige
      fuel oil. Polycyclic aromatic hydrocarbon concentrations, which were determined
      in gills and digestive glands, were higher in digestive glands. The
      methylphenantrene and dibenzothiophene profiles confirmed the real exposure of
      mussels to the fuel oil. Immune data analysis revealed that no differences
      between fuel-treated and control animals were found in the cellular immune
      parameters measured (hemocyte viability, phagocytic activity, nitric oxide
      production, and chemiluminescence emission). In addition, histologic observations
      did not reveal tissue lesions in any of the samples, probably because of the
      short time of fuel-oil exposure. In contrast, significant differences were found
      in serum protein concentration and lysozyme activity between the fuel-treated
      mussels and controls. However, these humoral immune parameters were dependant on
      numerous environmental and physiologic factors, so it was difficult to ascertain
      the real effect of the fuel oil on their variability. Because hemocytes are the
      primary line of defense of bivalve mollusks, the results obtained in the present
      study suggest that the mussel immune system was not significantly affected by
      exposure to the Prestige fuel oil.

PMID- 17180483
TI  - Studies of uptake, elimination, and late effects in Atlantic salmon (Salmo salar)
      dietary exposed to Di-2-ethylhexyl phthalate (DEHP) during early life.
AB  - The phthalate esters are a group of industrial chemicals considered to have
      endocrine-disrupting properties. The most common tonnage product among these, di
      2-ethylhexyl phthalate (DEHP), is widely spread in the environment. The
      objectives with the present work were to study uptake and metabolism of orally
      administered DEHP and its major metabolite mono-2-ethyl hexyl phthalate (MEHP)
      and to evaluate the impact of early life exposure on sex differentiation in
      Atlantic salmon. The feeding with contaminated diet started immediately after
      yolk sac resorption and continued for 4 weeks. Nominal concentrations of DEHP in
      the diet were 400 (measured 359), 800 (measured 827), and 1500 (measured 1648) mg
      DEHP/kg and a control group was fed food mixed with solvent. After the exposure
      period, fish were fed non-contaminated diet until final sampling 4 months post
      exposure. There were no effects on growth or survival of the fish and no late
      effects on hepatosomatic index or sex ratio. However, the histological
      examination of gonads from fish exposed to 1500 mg DEHP/kg revealed a small but
      significant incidence (3%) of intersex fish (ovo-testis). Chemical residues of
      DEHP and MEHP were analyzed weekly during the first 3 months of the post-exposure
      period. Both DEHP and MEHP were rapidly eliminated to near background levels
      within one week post exposure. The study indicates that exposure of Atlantic
      salmon to relatively high concentrations of DEHP during a sensitive part of the
      life cycle may interfere with gonad differentiation.

PMID- 17180484
TI  - Alpha-tocopheryl succinate (alpha-TOS) modulates human prostate LNCaP xenograft
      growth and gene expression in BALB/c nude mice fed two levels of dietary soybean
      oil.
AB  - BACKGROUND: Malignancy of the prostate constitutes a leading cause of cancer
      related deaths in America and Europe. Alpha-tocopheryl succinate (alpha-TOS) has
      been shown to inhibit human prostate cancer growth in vitro, via several
      mechanisms, including inhibiting prostate-specific antigen (PSA) and vascular
      endothelial growth factor (VEGF) expressions. The route of alpha-TOS
      administration has a profound effect on its antitumor activity, and few studies
      have investigated its effects on prostate cancer growth in vivo. AIM OF THE
      STUDY: The present study tested the hypothesis that alpha-TOS wil reduce the
      growth of human prostate LNCaP tumors in mice fed low (7%) and high (20%) levels
      of dietary soybean oil, compared to the controls receiving vehicle, by modulating
      PSA and VEGF gene expressions in the tumor tissue. METHODS: BALB/c nude mice (n =
      42) were subcutaneously inoculated with 1 x 10(6) LNCaP cells and assigned to one
      of four dietary groups; 7% or 20% soybean oil diet with or without alpha-TOS
      treatment. Three weeks later, mice received daily intraperitoneal injections of
      alpha-TOS (100 mg/kg body weight) in sesame seed oil (SSO) for two weeks;
      controls received SSO injections. Tumor volumes were recorded weekly. Sera,
      liver, and tumor tissues were collected at seven weeks for serum PSA,
      testosterone and alpha-tocopherol analyses, histopathological examination, and
      reverse transcription and polymerase chain reaction (RT-PCR) amplification of PSA
      and VEGF gene fragments in tumors. Relative quantification of gene expression was
      performed using real-time PCR. P < or = 0.05 was considered significant. RESULTS:
      Intraperitoneal injections of alpha-TOS caused decreased tumor growth in both
      groups (7% and 20% fat, P < 0.05), versus controls. alpha-TOS treatment
      significantly reduced serum PSA and testosterone levels in comparison to the SSO
      treated controls (P < 0.05). Control tumors had a greater degree of angiogenesis
      than alpha-TOS tumors, as demonstrated by the greater number of blood-filled
      vessels. PSA and VEGF mRNA expressions, were also reduced with alpha-TOS
      treatment (P < 0.05), revealing the possible molecular mechanisms of growth
      inhibition of LNCaP xenografts by alpha-TOS. CONCLUSIONS: Our study shows
      significant reduction in LNCaP xenograft growth with alpha-TOS treatment in nude
      mice fed a low (7%) and high (20%) fat soybean oil diets versus controls. Serum
      PSA and testosterone, tumor angiogenesis, and PSA and VEGF mRNA expressions were
      markedly reduced by alpha-TOS administration, suggesting a possible role of alpha
      TOS as a chemotherapeutic agent in human prostate cancer, and warrants further
      investigations on the dose and delivery of alpha-TOS in humans.

PMID- 17180488
TI  - Gravitational biology. Proceedings of the 2004 "Gravimeeting". Erlangen, Germany.

PMID- 17180485
TI  - Effect of a milk drink supplemented with whey peptides on blood pressure in
      patients with mild hypertension.
AB  - BACKGROUND: Inhibition of the angiotensin I-converting enzyme (ACE) is a widely
      used principle for the treatment of hypertension. Fermentation of milk proteins
      was shown to lead to the formation of peptides with ACE-inhibiting activity. Milk
      products with ACE-inhibiting peptides may provide a useful approach to prevent or
      treat hypertension. AIM OF THE STUDY: To investigate the effect of a milk drink
      supplemented with whey peptides on blood pressure in mildly hypertensive
      subjects. METHODS: A randomized, placebo-controlled, double blind clinical trial
      in two parallel groups was performed. A total of 54 hypertensive patients
      received either 125 ml of a milk drink supplemented with whey peptides every
      morning or a control product for 12 weeks after a run-in period of 2 weeks.
      Previous in vitro tests of the whey powder demonstrated ACE-inhibitory activity.
      Blood pressure was measured at 0, 2, 4, 8, and 12 weeks. Fasting blood samples
      were collected at 0, 4, 8, and 12 weeks for analysis of metabolic and
      inflammatory variables. RESULTS: Resting systolic and diastolic blood pressure
      values did not change in the milk drink group 144.1 +/- 8.6/91.0 +/- 5.5 mmHg at
      baseline vs. 143.7 +/- 13.5/90.4 +/- 6.5 mmHg after 12 weeks. In the control
      group systolic (p = 0.0431) and diastolic (p = 0.0081) blood pressure was
      significantly reduced 140.6 +/- 11.7/90.3 +/- 5.8 mmHg at baseline vs. 137.0 +/-
      14.4/87.7 +/- 6.6 mmHg after 12 weeks. There was no difference between the two
      groups at any time point. No changes were seen when the results of the 24-h
      continuous blood pressure monitoring were compared after 12 weeks. No significant
      changes were detected for circulating levels of selected inflammation markers
      (interleukin (IL)-6, C-reactive protein (CRP), number of leukocytes, and
      plasminogen activator inhibitor-1 (PAI-1) as well as for metabolic variables
      (insulin, plasma glucose, and lipids). CONCLUSIONS: The daily consumption of 125
      ml of a milk drink supplemented with whey peptides was not found to reduce blood
      pressure and/or inflammation markers in mildly hypertensive subjects, although
      preceding in vitro tests showed a potent ACE-inhibition.

PMID- 17180489
TI  - Gravitational biology within the German Space Program: goals, achievements, and
      perspectives.
AB  - Gravity plays an important role for the evolution, orientation and development of
      organisms. Most of us, however, tend to overlook its importance because--due to
      its constant presence from the beginning of evolution some 4 billion years ago-
      this environmental parameter is almost hardwired into our interpretation of
      reality. This negligence of gravity is the more surprising as we all have our
      strong fights with this factor, especially during the very early and again during
      the late phases of our lives. On the other hand, scientists have been fascinated
      to observe the effects of gravity especially on plants and microorganisms for
      more than a hundred years, since Darwin and Sachs demonstrated the role of the
      root cap for downward growing plants. Different experimental approaches are
      nowadays available in order to change the influence of gravity and to study the
      corresponding influences on the physiology of biological systems. With the advent
      of spaceflight, a long-term nearly nullification of gravity is possible.
      Utilisation of this so-called "microgravity" condition for research in life
      sciences thus became an important asset in the space programs of various space
      agencies around the world. The German Space Life Sciences Program is managed-
      like all other space programs and activities in Germany--by the German Aerospace
      Center (DLR) in its role as space agency for Germany. Within the current space
      program, approved by the German government in May 2001, the overall goal for its
      life sciences part was defined as to gain scientific knowledge and to disclose
      new application potential by research under space conditions, especially by
      utilising the microgravity environment of the International Space Station. Three
      main scientific fields have been identified in collaboration with the scientific
      community: integrative human physiology, biotechnological applications of the
      microgravity environment, and fundamental biology of gravity and radiation
      responses (i.e., gravitational and radiation biology). In the present
      contribution, specific goals as well as achievements and perspectives of research
      in gravitational biology are given. In addition, some information is provided on
      spaceflight opportunities available.

PMID- 17180490
TI  - Indications for acceleration-dependent changes of membrane potential in the
      flagellate Euglena gracilis.
AB  - The effects of the calcium sequester EGTA on gravitactic orientation and membrane
      potential changes in the unicellular flagellate Euglena gracilis were
      investigated during a recent parabolic-flight experiment aboard of an Airbus
      A300. In the course of a flight parabola, an acceleration profile is achieved
      which yields subsequently about 20 s of hypergravity (1.8 g(n)), about 20 s of
      microgravity, and another 20 s of hypergravity phases. The movement behavior of
      the cells was investigated with real-time, computer-based image analysis.
      Membrane potential changes were detected with a newly developed photometer which
      measures absorption changes of the membrane potential-sensitive probe oxonol VI.
      To test whether the data obtained by the oxonol device were reliable, the signal
      of non-oxonol-labelled cells was recorded. In these samples, no absorption shift
      was detected. Changes of the oxonol VI signals indicate that the cells depolarize
      during acceleration (very obvious in the step from microgravity to hypergravity)
      and slightly hyperpolarize in microgravity, which can possibly be explained with
      the action of Ca-ATPases. These signals (mainly the depolarization) were
      significantly suppressed in the presence of EGTA (5 mM). Gravitaxis in parallel
      was also inhibited after addition of EGTA. Initially, negative gravitaxis was
      inverted into a positive one. Later, gravitaxis was almost undetectable.

PMID- 17180491
TI  - Graviresponses of Paramecium biaurelia during parabolic flights.
AB  - The thresholds of graviorientation and gravikinesis in Paramecium biaurelia were
      investigated during the 5th DLR (German Aerospace Center) parabolic-flight
      campaign at Bordeaux in June 2003. Parabolic flights are a useful tool for the
      investigation of swimming behaviour in protists at different accelerations. At
      normal gravity (1 g) and hypergravity (1 g to 1.8 g), precision of orientation
      and locomotion rates depend linearly on the applied acceleration as seen in
      earlier centrifuge experiments. After transition from hypergravity to decreased
      gravity (minimal residual acceleration of <10(-2) g), graviorientation as well as
      gravikinesis show a full relaxation with different kinetics. The use of twelve
      independent cell samples per flight guarantees high data numbers and secures the
      statistical significance of the obtained data. The relatively slow change of
      acceleration between periods of microgravity and hypergravity (0.4 g/s) enabled
      us to determine the thresholds of graviorientation at 0.6 g and of gravikinesis
      at 0.4 g. The gravity-unrelated propulsion rate of the sample was found to be 874
      microm/s, exceeding the locomotion rate of horizontally swimming cells (855
      microm/s). The measured thresholds of graviresponses were compared with data
      obtained from earlier centrifuge experiments on the sounding rocket Maxus-2.
      Measured thresholds of gravireactions indicate that small energies, close to the
      thermal noise level, are sufficient for the gravitransduction process. Data from
      earlier hypergravity experiments demonstrate that mechanosensitive ion channels
      are functioning over a relative wide range of acceleration. From this, we may
      speculate that gravireceptor channels derive from mechanoreceptor channels.

PMID- 17180492
TI  - Gravisusception by buoyancy: a mechanism ubiquitous among fungi?
AB  - Gravitropism is ubiquitous among the fungal taxa; however, the mechanism(s) of
      gravisusception have overall remained obscure so far. In the vegetative
      sporangiophore of the zygomycete Phycomyces blakesleeanus some 200 large lipid
      globules form a conspicuous spherical complex which is positioned in a dense mesh
      of filamentous actin about 100 microm below the growing tip of the apex.
      Experimental suppression of that complex by transient growth at low temperature
      greatly diminishes the gravitropic response of the sporangiophore. With respect
      to size and abundance of the globules, the complex of lipid globules meets basic
      physical criteria for a possible function of gravisusception. Accumulations of
      similar lipid globules of critical size are documented in the apex of
      gravitropically growing hyphae of the endomycorrhizal fungus Gigaspora margarita
      (Glomeromycota) and have been described in the hyphal apices of members of
      various fungal phyla. We suppose that--in contrast to plants which use starch as
      a carbon storage and amyloplasts as statoliths--the fungi utilise the buoyancy of
      carbon-storing oil droplets for gravisusception.

PMID- 17180493
TI  - Gravity-induced absorption changes in Phycomyces blakesleeanus during parabolic
      flights: first spectral approach in the visible.
AB  - Gravity-induced absorption changes as experienced during a series of parabolas on
      the Airbus 300 Zero-G have been measured previously pointwise on the basis of
      dual-wavelength spectroscopy. Only the two wavelengths of 460 and 665 nm as
      generated by light-emitting diodes have been utilised during our first two
      parabolic-flight campaigns. In order to gain complete spectral information
      throughout the wavelength range from 400 to 900 nm, a miniaturized rapid scan
      spectrophotometer was designed. The difference of spectra taken at 0 g and 1.8 g
      presents the first gravity-induced absorption change spectrum measured on wild
      type Phycomyces blakesleeanus sporangiophores, exhibiting a broad positive hump
      in the visible range and negative values in the near infrared with an isosbestic
      point near 735 nm. The control experiment performed with the stiff mutant A909 of
      Phycomyces blakesleeanus does not show this structure. These results are in
      agreement with those obtained with an array spectrophotometer. In analogy to the
      more thoroughly understood so-called light-induced absorption changes, we assume
      that gravity-induced absorption changes reflect redox changes of electron
      transport components such as flavins and cytochromes localised within the plasma
      membrane.

PMID- 17180494
TI  - Rhizoids and protonemata of characean algae: model cells for research on
      polarized growth and plant gravity sensing.
AB  - Gravitropically tip-growing rhizoids and protonemata of characean algae are well
      established unicellular plant model systems for research on gravitropism. In
      recent years, considerable progress has been made in the understanding of the
      cellular and molecular mechanisms underlying gravity sensing and gravity-oriented
      growth. While in higher-plant statocytes the role of cytoskeletal elements,
      especially the actin cytoskeleton, in the mechanisms of gravity sensing is still
      enigmatic, there is clear evidence that in the characean cells actin is
      intimately involved in polarized growth, gravity sensing, and the gravitropic
      response mechanisms. The multiple functions of actin are orchestrated by a
      variety of actin-binding proteins which control actin polymerisation, regulate
      the dynamic remodelling of the actin filament architecture, and mediate the
      transport of vesicles and organelles. Actin and a steep gradient of cytoplasmic
      free calcium are crucial components of a feedback mechanism that controls
      polarized growth. Experiments performed in microgravity provided evidence that
      actomyosin is a key player for gravity sensing: it coordinates the position of
      statoliths and, upon a change in the cell's orientation, directs sedimenting
      statoliths to specific areas of the plasma membrane, where contact with membrane
      bound gravisensor molecules elicits short gravitropic pathways. In rhizoids,
      gravitropic signalling leads to a local reduction of cytoplasmic free calcium and
      results in differential growth of the opposite subapical cell flanks. The
      negative gravitropic response of protonemata involves actin-dependent relocation
      of the calcium gradient and displacement of the centre of maximal growth towards
      the upper flank. On the basis of the results obtained from the gravitropic model
      cells, a similar fine-tuning function of the actomyosin system is discussed for
      the early steps of gravity sensing in higher-plant statocytes.

PMID- 17180495
TI  - Gravity: one of the driving forces for evolution.
AB  - Mechanical load is 10(3) larger for land-living than for water-living organisms.
      As a consequence, antigravitational material in form of compound materials like
      lignified cell walls in plants and mineralised bones in animals occurs in land
      living organisms preferentially. Besides cellulose, pectic substances of plant
      cell walls seem to function as antigravitational material in early phases of
      plant evolution and development. A testable hypothesis including vesicular
      recycling processes into the tensegrity concept is proposed for both sensing of
      gravitational force and responding by production of antigravitational material at
      the cellular level.

PMID- 17180496
TI  - Halotolerance is enhanced in carrot callus by sensing hypergravity: influence of
      calcium modulators and cytochalasin D.
AB  - Carrot callus was centrifuged at 10 g and compared to callus growing at 1 g on
      agar in the presence of increasing sodium chloride concentrations. Growth after
      14 days was enhanced in the centrifuged samples versus samples kept at 1 g. This
      effect was not found when the samples were grown on potassium chloride. At 50 mM
      NaCl, the calcium ionophore ionomycin was applied to centrifuged and
      noncentrifuged callus samples. In both experiments, the growth of callus
      increased with increasing ionomycin concentrations but under 10 g this increase
      was more enhanced. As inhibitors of calcium influx, lanthanum and gadolinium
      chloride were chosen in the presence of 50 mM NaCl. Both inhibitors inhibited
      growth at 1 g at low concentrations of around 2 microM, whereas the centrifuged
      samples were not or much less so inhibited. We tested an involvement of actin by
      application of cytochalasin D to callus grown in the presence of 50 mM NaCl. In
      both types of samples, growth at 1 g and growth at 10 g, cytochalasin D enhanced
      growth but the effect was clearly stronger at 10 g than at 1 g. As increased
      halotolerance was only observed in the presence of increased sodium ions, not
      potassium ions, and as halotolerance is known to be induced by an influx of
      calcium, the data suggest that a calcium influx induced by hypergravity and
      possibly modulated by actin caused the observed increase in halotolerance at 10
      g.

PMID- 17180497
TI  - Microgravity-related changes in gene expression after short-term exposure of
      Arabidopsis thaliana cell cultures.
AB  - Cell cultures of Arabidopsis thaliana (cv. Columbia) were used to screen for
      early alterations in gene expression as a response to altered gravitational
      fields. Genes of interest were selected from a larger group whose expression was
      altered under hypergravity (microarray study; M. Martzivanou and R. Hampp,
      Physiol. Plant. 118: 221-231, 2003). Transcriptional changes of these genes were
      studied within a time frame of up to 10 min of exposure to microgravity in a
      sounding-rocket experiment, to clinorotation (random positioning machine), and to
      hypergravity (8 g). We could identify a set of nine genes (mainly components of
      signaling chains) with increased transcript levels after about 6 min of exposure
      to microgravity. As clinorotation and hypergravity treatment did not alter the
      respective transcript amounts, we assume that the identified genes could be
      involved in a microgravity-related response.

PMID- 17180498
TI  - Inositol 1,4,5-trisphosphate and Ran expression during simulated and real
      microgravity.
AB  - In order to gain further insight into the signal transduction pathway concerning
      gravitropism, we studied the expression profiles of mRNA in etiolated sunflower
      (Helianthus annuus L.) seedlings. Differential-display reverse transcriptase PCR
      product assayed by capillary electrophoresis revealed the small GTPase Ran,
      regulating nuclear import and export of proteins. Parallel analysis of inositol
      1,4,5-trisphosphate (Ins(1,4,5)P3) release by a highly advanced system of metal
      dye detection combined with high-performance liquid chromatography provided
      evidence that the second messenger Ins(1,4,5)P3 is modulated by changes of the
      gravity vector. Investigations by fast clinorotation and sounding rockets
      established a positive correlation between the Ins(1,4,5)P3 level and the
      expression rate of Ran mRNA during simulated and real microgravity. Since an
      asymmetric distribution of auxin during graviresponse is suggested to induce
      differential cell elongation, additional information on the perception and
      transduction pathways was achieved by auxin stimulation experiments. While we
      were able to demonstrate an auxin-dependent production of Ins(1,4,5)P3, the
      expression of Ran mRNA was not affected by auxin. Finally, besides the
      phosphoinositide system as one element of the signal transduction chain linking
      graviperception to graviresponse, a Ran-mediated interaction model of
      extracellular microgravity signal perception and intercellular transduction
      pathway is proposed.

PMID- 17180499
TI  - Auxin transport and gravitational research: perspectives.
AB  - Gravity is a fundamental factor which affects all living organisms. Plant
      development is well adapted to gravity by directing roots downward and shoots
      upwards. For more than a century, plant biologists have been fascinated to
      describe the molecular mechanisms underlying the gravitropic response of plants.
      Important progress towards signal perception, transduction, and response has been
      made, but new tools are beginning to uncover the regulatory networks for
      gravitropic control. We summarise recent progress in study of gravitropism and
      discuss strategies to identify the molecular basis of the gravity response in
      Arabidopsis thaliana. This will put us on a road towards the molecular systems
      biology of the Arabidopsis gravitropic response.

PMID- 17180501
TI  - Morphometric investigations of sensory vestibular structures in tadpoles (Xenopus
      laevis) after a spaceflight: implications for microgravity-induced alterations of
      the vestibuloocular reflex.
AB  - In lower vertebrates, gravity deprivation by orbital flights modifies the
      vestibuloocular reflex. Using the amphibian Xenopus laevis, the experiments
      should clarify to which extent macular structures of the labyrinth are
      responsible for these modifications. In particular, the shape of otoconia and
      number and size of sensory macular cells expressing CalBindin were considered.
      CalBindin is common in mature sensory cells including vestibular hair cells and
      is probably involved in otoconia formation. Two developmental stages were used
      for this study: stage 26/27 embryos, which were unable to perform the roll
      induced vestibuloocular reflex (rVOR) at onset of microgravity, and stage 45
      tadpoles, which had already developed the reflex. The main observations were that
      the developmental progress of the animals was not affected by microgravity; that
      in the young tadpole group with normal body shape the rVOR was not modified by
      microgravity, while in the older group with microgravity experience, the rVOR was
      augmented; and that significant effects on the shape of otoconia and on the
      number and size of CalBindin-expressing cells of the labyrinthine maculae cells
      were absent. In addition, behavioural data were never significantly correlated
      with morphological features of macular structures such as size and number of
      CalBindin-expressing cells. It is postulated that mechanisms of vestibular
      adaptation to microgravity during early development are probably based on
      mechanisms located in central structures of the vestibular system.

PMID- 17180500
TI  - Gravitropic plant growth regulation and ethylene: an unsought cardinal coordinate
      for a disused model.
AB  - According to the Cholodny-Went hypothesis, gravitropic differential growth is
      brought about by the redistribution of auxin (indolyl-3-acetic acid, IAA). We
      reinvestigated the relevance of different auxins and studied the role of ethylene
      in hypocotyls of sunflower and shoots and roots of rye and maize seedlings.
      Incubation of coleoptiles and of sunflower hypocotyls in solutions of IAA and
      dichlorophenoxyacetic acid as well as naphthylacetic acid resulted in a two- to
      threefold length increase compared to water controls. In spite of this pronounced
      general effect on elongation growth, gravi-curvature was similar to water
      controls. In contrast to this, inhibition of ethylene synthesis by
      aminoethoxyvinylglycine prevented differential growth of both hypocotyls and
      coleoptiles and of roots of maize. In horizontally stimulated maize roots growing
      on surfaces, inhibition of ethylene perception by methylcyclopropene inhibited
      roots to adapt growth to the surface, resulting in a lasting vertical orientation
      of the root tips. This effect is accompanied by up- and down-regulation of a
      number of proteins as detected by two-dimensional matrix-assisted laser
      desorption-ionization time-of-flight mass spectrometry. Together the data query
      the regulatory relevance of IAA redistribution for gravitropic differential
      growth. They corroborate the crucial regulatory role of ethylene for gravitropic
      differential growth, both in roots and coleoptiles of maize as well as in
      hypocotyls.

PMID- 17180502
TI  - On the role of the central nervous system in regulating the mineralisation of
      inner-ear otoliths of fish.
AB  - Stato- or otoliths are calcified structures in the organ of balance and
      equilibrium of vertebrates, the inner ear, where they enhance its sensitivity to
      gravity. The compact otoliths of fish are composed of the calcium carbonate
      polymorph aragonite and a small fraction of organic molecules. The latter form a
      protein skeleton which determines the morphology of an otolith as well as its
      crystal lattice structure. This short review addresses findings according to
      which the brain obviously plays a prominent role in regulating the mineralisation
      of fish otoliths and depends on the gravity vector. Overall, otolith
      mineralisation has thus been identified to be a unique, neuronally guided
      biomineralisation process. The following is a hypothetical model for regulation
      of calcification by efferent vestibular neurons: (1) release of calcium at tight
      junctions in the macular epithelia, (2) macular carbonic anhydrase activity
      (which in turn is responsible for carbonate deposition), (3) chemical composition
      of matrix proteins. The rationale and evidence that support this model are
      discussed.

PMID- 17180503
TI  - Zebrafish and medaka as models for bone research including implications regarding
      space-related issues.
AB  - Teleost fish develop bones directly from mesenchymal condensations and from
      cartilage precursors. At the cellular level, the involved cell populations share
      many features with their mammalian counterparts. In addition, several genes are
      already described in fish showing high homology in amino acid sequence and
      expression with the corresponding genes of tetrapods that are involved in bone
      metabolism. Therefore, analysis of the underlying molecular mechanism in fish, in
      particular zebrafish and medaka, will increase the knowledge in teleosts.
      Furthermore, it will help to identify novel genes and regulatory pathways of bone
      homeostasis and skeletal disorders also in higher vertebrates, including
      disorders caused by altered gravity.

PMID- 17180504
TI  - Establishment of stable human fibroblast cell lines constitutively expressing
      active Rho-GTPases.
AB  - Small GTP-binding proteins of the Rho family (RhoA, Cdc42, Rac1) regulate the
      organisation and the turnover of the cell's cytoskeleton and adhesion structures.
      A significant function of these cellular structures is to translate and
      counterbalance forces applied to, or generated by, cells in order to maintain
      homeostasis and control cell movement. We therefore hypothesised that Rho-GTPases
      are directly involved in cellular gravity perception and may participate in the
      alterations induced in microgravity. To define an adequate cellular model
      allowing to investigate this issue, we have established stable cell lines
      constitutively expressing active forms of either RhoA, Cdc42, or Rac1. The three
      cell lines differ by morphology and by their ability to form filopodia,
      lamellipodia, and bundles of actin stress fibers. Overexpression of the active
      form of either RhoA, Cdc42, or Rac1 is compatible with cell viability and does
      not affect cell population doubling time. Thus, our series of mutant cells appear
      well suited to gain further knowledge on the molecular mechanisms of cellular
      gravity perception.

PMID- 17180505
TI  - Respiratory burst as a biomarker for stress responses.
AB  - A module for the detection of immunotoxic events within the test system Triple
      Lux to be used during spaceflights was developed. It is based on the production
      of reactive oxygen species within the respiratory burst during phagocytosis or
      after stimulation of the phagocytes with phorbol 12-myristate 13-acetate (PMA).
      For this purpose, luminol-dependent chemiluminescence was measured. The assays
      were carried out with polymorphonuclear leukocytes purified from sheep peripheral
      blood. The influence of hydrocortisone and Cd2+ on the respiratory burst in
      polymorphonuclear leukocytes was assayed. Hydrocortisone in concentrations
      between 10(-4) and 10(-9) mol/liter showed an immunostimulating effect after PMA
      treatment. An immunosuppressive effect was observed for Cd2+ in concentrations
      between 10(-4) and 10(-7) mol/liter. Cryoconservation, which has often been
      critical for primary cells, can be accomplished without any subsequent loss of
      function by freezing the cells in dimethyl sulfoxide-containing medium.

PMID- 17180506
TI  - Effects of altered gravity on the actin and microtubule cytoskeleton of human SH
      SY5Y neuroblastoma cells.
AB  - Human SH-SY5Y neuroblastoma cells were used to study the effects of altered
      gravity on the actin and microtubule cytoskeleton dynamics. A cholinergic
      stimulation of the cells during a 6 min period of changing gravity (3 parabolas)
      resulted in an enhanced actin-driven protrusion of evoked lamellipodia. Likewise,
      the spontaneous protrusive activity of nonactivated cells was promoted during
      exposure to changing gravity (6 up to 31 parabolas). Ground-based experiments
      revealed a similar enhancement of the spontaneous and evoked lamellar protrusive
      activity when the cells were kept at 2 g hypergravity for at least 6 min. This
      gravity response was independent of the direction of the acceleration vector in
      respect to the cells. Exposure of the cells to "simulated weightlessness"
      (clinorotation) had no obvious influence on this type of lamellar actin
      cytoskeleton dynamics. A 20 min exposure of the cells to simulated weightlessness
      or to changing gravity (6 to 31 parabolas) - but not to 2 g (hypergravity,
      centrifugation) - resulted in an altered arrangement of microtubules indicated by
      bending, turning, and loop formation. A similar altered arrangement was shown by
      microtubules which had polymerized into lamellipodia after release from a taxol
      block at simulated weightlessness (clinorotation) or during changing gravity (5
      parabolas). Our data suggest that in human SH-SY5Y neuroblastoma cells,
      microgravity affects the dynamics and spatial arrangement of microtubules but has
      no influence on the Rac-controlled lamellar actin cytoskeleton dynamics and cell
      spreading. The latter, however, seems to be promoted at hypergravity.

PMID- 17180507
TI  - Microgravity dependence of excitable biological and physicochemical media.
AB  - Neuronal tissue and especially the central nervous system (CNS) is an excitable
      medium. Self-organisation, pattern formation, and propagating excitation waves as
      typical characteristics in excitable media consequently have been found in
      neuronal tissue. The properties of such phenomena in excitable media do
      critically depend on the parameters (i.e., electromagnetic fields, temperature,
      chemical drugs) of the system and on small external forces to which gravity
      belongs. The spreading depression, a propagating excitation depression wave of
      neuronal activity, is one of the best described of the those wave phenomena in
      the CNS. Especially in the retina as a true part of the CNS it can be easily
      observed with optical techniques due to the high intrinsic optical signal of this
      tissue. Another of such waves in neuronal tissue is the propagating action
      potential in nerve fibres. In this paper, data from our laboratories concerning
      the influence of gravity on the velocity of propagating waves in excitable media
      are summarized mainly in terms of the retinal spreading depression and
      propagating action potentials. Additionally, we have used waves in gels of the
      Belousov-Zhabotinsky reaction as the physicochemical model system of biological
      activity as the properties of these waves follow the same theories as the
      spreading depression and action potentials and they have some striking
      similarities in wave behavior. Thus propagating Belousov-Zhabotinsky waves are
      described by their gravity dependence.

PMID- 17180508
TI  - Cytoskeleton changes and impaired motility of monocytes at modelled low gravity.
AB  - Investigations performed in space have shown that gravity changes affect
      important cellular mechanisms like proliferation, differentiation, genetic
      expression, cytoskeletal architecture, and motility in lymphocytes, monocytes,
      and other mammalian cells. In particular, a dramatic depression of the mitogenic
      in vitro activation of human peripheral blood lymphocytes was observed at low
      gravity. The hypothesis of the present work is that a reduced interaction between
      T lymphocytes and monocytes, essential for the second signalling pathway, might
      be one of the reasons for the observed depression of the in vitro activation of
      human lymphocytes. Cell motility and with it a continuous rearrangement of the
      cytoskeletal network within the cell is essential for cell-to-cell contacts.
      Whereas nonactivated lymphocytes in suspension are highly motile at low gravity,
      no data are available so far on the motility of adherent monocytes. It thus can
      be argued that impaired monocyte locomotion and cytoskeletal changes could be
      responsible for a reduced interaction of monocytes with T lymphocytes. In this
      study, the locomotion ability of J-111 cells, an adherent monocyte cell line,
      attached to colloidal gold particles on coverslips and exposed to modelled low
      gravity in the random positioning machine was found to be severely reduced
      compared with that of controls and the structures of actin, tubulin, and vinculin
      were affected.

PMID- 17180509
TI  - Cancer of unknown primary site: review of consecutive cases at the National
      Cancer Center Hospital of Japan.
AB  - BACKGROUND: Cancer of unknown primary (CUP) is not a rare clinical entity,
      accounting for 3%-5% of all solid malignancies. METHODS: We retrospectively
      reviewed 86 (38 male/48 female) patients with a diagnosis of CUP (exclusive of
      female patients with adenocarcinoma involving the axillary lymph nodes alone and
      patients with squamous cell carcinoma of the cervical lymph nodes) who were
      referred to the National Cancer Center Hospital between April 1996 and October
      2002. RESULTS: The median interval between the first visit to a local community
      hospital and referral to our hospital was 1 month (range, 1 to 45 months). The
      histological diagnosis was adenocarcinoma in 61 patients (71%), poorly
      differentiated carcinoma in 18 patients (21%), and squamous cell carcinoma in 4
      patients (5%). Twenty-three female patients had peritoneal carcinomatosis of
      adenocarcinoma. Seventy-eight patients (91%) received platinum-containing
      chemotherapy. Sixty-one of the 86 patients (71%) were categorized as a subgroup
      of CUP without a specific therapy, and 55 of these 61 patients (90%) received
      platinum-containing regimens. The median survivals of all 86 patients and the 61
      patients in the subgroup without a specific therapy in this series were 13 months
      and 11 months, respectively. CONCLUSION: In this series, the survival of the
      patients in the CUP subgroup without a specific therapy did not seem worse than
      that in previous reports. Empirical chemotherapy with platinum-containing
      regimens may benefit some CUP patients in a subgroup without a specific
      chemotherapy.

PMID- 17180510
TI  - p53 expression status is a significant molecular marker in predicting the time to
      endocrine therapy failure in recurrent breast cancer: a cohort study.
AB  - BACKGROUND: Hormone receptor status has been one of the most important factors in
      predicting the response to endocrine therapy in breast cancer patients. However,
      half of those patients with estrogen receptor-positive tumors do not respond to
      endocrine therapy. There have been no universal factors for predicting resistance
      to endocrine therapy in this population. Recently, p53 status has been
      extensively used as a predictive factor for response to systemic therapy, because
      tumor cells lacking p53 function do not respond to systemic therapy due to a
      failure in apoptosis. We therefore studied the relationship between the efficacy
      of endocrine therapy and biological factors, including p53. METHODS: The
      expression of p53, Ki67, and human epidermal growth factor receptor (HER)2 was
      examined by immunostaining in the primary tumors of 53 patients who received
      endocrine therapy for recurrent or advanced breast cancer. The following clinical
      factors were also analyzed: site treated, disease-free interval, and response to
      first-line endocrine therapy. To evaluate the significance of these factors, time
      to endocrine therapy failure (TTEF), or the total duration of sequential
      endocrine therapies was adopted as representing the clinical outcome. RESULTS:
      The median TTEF was 16.1 months (range, 2.5-89.9 months). Multivariate analysis
      showed significantly reduced TTEF associated with no response to first-line
      endocrine therapy (P = 0.006 and P = 0.002 in all patients and in recurrent
      patients, respectively) and associated with positive p53 expression (P = 0.066
      and P = 0.004, respectively). CONCLUSION: p53 expression status was a significant
      molecular marker as well as the response to first-line endocrine therapy for
      predicting TTEF in recurrent breast cancer with hormone-sensitive disease.

PMID- 17180511
TI  - A low-dose combination therapy of interleukin-2 and interferon-alpha is effective
      for lung metastasis of renal cell carcinoma: a multicenter open study.
AB  - BACKGROUND: To confirm the usefulness of a combination therapy of interleukin-2
      (IL-2) and interferon-alpha (IFN-alpha) against metastatic renal cell carcinoma,
      the recommended dose of IFN-alpha to use in combination with low-dose IL-2 was
      determined (phase 1). Efficacy and safety at this dose was evaluated (phase 2).
      METHODS: In phase 1, the dose of IL-2 was fixed at 0.7 x 10(6) Japan reference
      unit (JRU)/person for 5 days a week. The dose of IFN-alpha was increased from 3 x
      10(6) IU for 3 days a week (level I) to 6 x 10(6) IU for 3 days a week (level II)
      and to 6 x 10(6) IU for 5 days a week (level III). RESULTS: In phase 1, 10
      patients were registered, with 9 (3 at each level) able to be evaluated. Because
      grade 3 and grade 4 neutropenia were observed at level III in 1 patient each,
      level II was found to be the recommended regimen. The response rate in phase 1
      was 44.4% (4/9). In phase 2, 46 patients were registered, with a response rate in
      37 patients, classified as per protocol set (PPS), of 21.6% (8/37). Toxicities
      observed were primarily flu-like symptoms due to cytokines, and gastrointestinal
      symptoms. Leukocyte abnormalities were observed, but they were milder and
      tolerable. CONCLUSION: In the 46 patients evaluated in phase 1 and phase 2, the
      response rate was 26.1% (12/46), being highest in 38.7% (12/31) of those who were
      nephrectomized, and with only lung metastases.

PMID- 17180512
TI  - "Watch-and-see" policy for the clinically positive neck in head and neck cancer
      treated with chemoradiotherapy.
AB  - BACKGROUND: Chemoradiotherapy (CRT) is becoming more widely used for head and
      neck cancer. However, there are conflicting theories regarding the best
      management options for patients with advanced nodal disease. METHODS: From 1990
      to 1999, we treated 96 patients with N1-N2 neck disease by concomitant CRT for
      organ preservation, using weekly carboplatin or a low daily dose of cisplatin,
      followed by a "watch-and-see" policy for the neck. In the present study, we
      retrospectively analyzed the treatment outcome in 63 of these patients who
      received definitive CRT for primary and neck diseases and were monitored for neck
      disease for more than 2 years. RESULTS: In 12 of the 22 (55%) N1 patients, CRT
      successfully controlled the neck disease. CRT was successful in 18 of the 41
      (44%) patients with N2 disease. In 6 (60%) of 10 patients with residual or
      recurrent N1 disease, salvage surgery was successful. Of the 23 patients with
      residual or recurrent N2 disease, salvage surgery was successful in 8 patients
      (35%). The group of patients who showed a clinical complete response (CCR) to CRT
      had an overall survival rate of 62.4% (33 patients), whereas for those with a
      less than complete response (<CCR), the figure was 13.3% (30 patients; P <
      0.001). Among the <CCR-neck group, patients who underwent neck dissection (ND) as
      well (n = 20) did not have a significantly better overall survival than those who
      did not undergo ND (n = 10; P = 0.069). CONCLUSION: We propose a treatment plan
      for neck disease that involves observing the neck closely following CRT. ND
      should be planned only when there is evidence that neck disease exists.

PMID- 17180513
TI  - In vitro chemosensitivity test to predict chemosensitivity for paclitaxel, using
      human gastric carcinoma tissues.
AB  - BACKGROUND: Therapy guided by chemotherapy sensitivity and resistance assays may
      lead to rational treatment decisions. Paclitaxel, one of several new drugs for
      gastric carcinoma, has not been extensively evaluated by in vitro
      chemosensitivity tests. METHODS: Chemosensitivity testing by histoculture drug
      response assay (HDRA) was performed with fresh specimens of primary tumor from
      113 patients with gastric carcinoma. The test was performed in medium containing
      paclitaxel at three different concentrations for the initial 45 samples.
      Correlations between the results of chemosensitivity testing, determined at the
      optimal concentration, and the patients' clinicopathologic factors and outcome
      were then assessed for all patients. RESULTS: By analyzing the initial 45
      samples, 10 microg/ml was considered the optimal concentration of paclitaxel for
      this test. HDRA was successfully performed for 100 of 113 samples and
      chemosensitivity, calculated as the percentage of optical density of a tumor
      treated with anticancer drugs in relation to the optical density of the tumor
      cultured in the medium only, was distributed widely at this concentration. No
      significant correlation was observed between chemosensitivity and age, sex,
      clinical stage, histopathologic type, and outcome of patients with gastric
      carcinoma. CONCLUSION: A histoculture drug response assay can now be performed to
      predict the chemosensitivity of paclitaxel at the concentration found in the
      current study. The accuracy of the assay to actually predict survival needs to be
      validated by a prospective clinical trial involving patients who have received
      paclitaxel in the postoperative adjuvant setting.

PMID- 17180514
TI  - Dose escalation study of docetaxel and nedaplatin in patients with relapsed or
      refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5
      fluorouracil, and radiation.
AB  - BACKGROUND: Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil
      (5FU) has been playing an important role in the treatment of esophageal cancer,
      but some patients are not curable or have recurrent lesions. However, few
      chemotherapeutic regimens are available for such patients. Docetaxel and
      nedaplatin are active for esophageal cancer. We conducted a dose-escalation study
      of docetaxel and nedaplatin as second line-chemotherapy after definitive
      chemoradiation in patients with relapsed or refractory squamous cell carcinoma of
      the esophagus after chemoradiation. METHODS: Nedaplatin was administered on day 1
      and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation
      was based on the dose-limiting toxicity (DLT) observed during the first cycle.
      RESULTS: Twelve patients were enrolled. At a docetaxel dose of 30 mg/m(2) and a
      nedaplatin dose of 80 mg/m(2), one grade 4 neutropenia occurred and caused one
      treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and
      80 mg/m(2), respectively, two grade 4 neutropenias and one grade 2 thrombopenia
      occurred and caused three treatment breaks longer than 2 weeks. Therefore, the
      maximum tolerated dose was established at this dose level. Two grade 3 anorexias
      and one grade 3 nausea occurred, but other non-hematological toxicities were
      generally mild. Responses were seen in one-fourth of the 12 patients, including
      one complete remission. CONCLUSION: The recommended doses of docetaxel and
      nedaplatin were 30 and 80 mg/m(2), respectively. This combination could be a
      potential second-line treatment for this target population.

PMID- 17180515
TI  - Inflammatory pseudotumor of the lung: clinicopathological analysis in seven adult
      patients.
AB  - BACKGROUND: As the origin and pathology of inflammatory pseudotumor is not
      clearly understood, there has recently been some confusion regarding the
      diagnosis of inflammatory pseudotumor. METHODS: We performed clinicopathological
      analyses in seven patients with inflammatory pseudotumors of the lung
      histologically diagnosed after surgical resection. The seven patients, selected
      from patients admitted to Kawasaki Medical School Hospital between April 1989 and
      December 2005, consisted of four men and three women (average age, 60.4 years).
      The detection method was from clinical symptoms in two patients and from health
      examinations in five patients. RESULTS: Five patients had a solitary nodular
      shadow on chest radiographs and the other two patients had multiple shadows.
      Because it was difficult to distinguish pseudotumor from lung cancer by chest
      computed tomography in the five patients showing a solitary nodular shadow, the
      final diagnosis was obtained by surgical resection. In the other two patients,
      with multiple shadows, one of whom had nodular shadows with cavitary lesions,
      surgical resection was performed to distinguish the pseudotumor from metastatic
      lung cancer. The histological types according to the criteria of Matsubara were
      fibrous histiocytic in five patients, organizing pneumonia in one, and
      lymphoplasmocytic in one. The histological types according to the World Health
      Organization criteria were compact spindle-cell pattern in six patients and
      hypocellular fibrous pattern in one. CONCLUSION: Because it is difficult to make
      a preoperative diagnosis of inflammatory pseudotumor by radiological findings or
      histological findings using specimens obtained by transbronchial lung biopsy,
      surgical resection, such as video-assisted thoracic surgery or open lung biopsy,
      is required to differentiate inflammatory pseudotumors from primary or metastatic
      lung cancers.

PMID- 17180516
TI  - Intrapleural extravasation of epirubicin, 5-fluouracil, and cyclophosphamide,
      treated with dexrazoxane.
AB  - The extravasation of DNA-binding vesicant drugs, such as epirubicin, is a feared
      complication of chemotherapy and can lead to extensive damage at injury sites. We
      describe a 56-year-old woman with breast cancer who received adjuvant
      chemotherapy after a breast-preserving surgical procedure. Due to catheter tip
      misplacement, epirubicin, 5-fluouracil, and cyclophosphamide were administered
      intrapleurally. To minimize long-term sequelae, flushing of the cavities and
      systemic administration of steroids were performed. Besides this treatment,
      empirically, 3-day therapy with dexrazoxane was added to prevent tissue damage
      and the risk of cardiac damage. Because of the potential benefits of dexrazoxane
      and its relatively mild side effects, its use should be considered in cases of
      the intrapleural extravasation of anthracyclines. We do emphasis the need for
      stringent surgical and oncological nursing procedures when using central venous
      access catheters in oncology.

PMID- 17180517
TI  - Unresectable gastric cancer with multiple liver metastases effectively treated
      with combined paclitaxel and doxifluridine chemotherapy.
AB  - We report a 72-year-old man who was diagnosed by gastroscopy as having a type III
      poorly differentiated adenocarcinoma in the lesser curvature, with the longest
      diameter being 10 cm. An abdominal computed tomography (CT) scan revealed
      multiple liver metastases, thickening of the gastric wall, and an enlarged
      paraaortic lymph node. The serum carcinoembryonic antigen (CEA) level was 60
      ng/ml and the carbohydrate antigen (CA) 19-9 level was 1355 U/ml. The patient
      received combined chemotherapy with doxifluridine (800 mg/body per day) and
      paclitaxel (one course comprised three weekly infusions at a dose of 70 mg/m(2)
      followed by 1-week rest). After the completion of three courses, the patient
      achieved a complete response (CR), with complete disappearance of the primary
      tumor, the metastatic foci in the liver, and the enlarged abdominal lymph nodes;
      as well, the tumor markers were normalized. Adverse effects included only mild
      anorexia that was limited to grade 1. He maintained a CR for 1 year and 2 months.
      Combination chemotherapy with paclitaxel and doxifluridine can be an effective
      treatment for unresectable advanced gastric carcinoma.

PMID- 17180518
TI  - Clear cell tumor of the lung.
AB  - Clear cell tumor of the lung is a rare benign tumor. We report herein a case of
      clear cell tumor of the lung. A 45 year-old woman with a round mass lesion of
      approximately 2 cm diameter on chest X-ray underwent a thoracotomy. Pathologic
      examination revealed sheets of large round or polygonal cells with clear
      cytoplasm and immunoreactive positivity for HMB-45 and vimentin. Investigation
      with abdominal CT scans showed no evidence of renal disease, and the tumor was
      diagnosed as clear cell tumor of the lung.

PMID- 17180519
TI  - The therapeutic challenge of a nonresectable solitary fibrous tumor in a
      hypoglycemic patient.
AB  - We report a patient with a nonresectable histologically benign solitary fibrous
      tumor who suffered from paraneoplastic non-islet cell tumor hypoglycemia (NICTH).
      Diagnostic workup revealed malignant characteristics in which the tumor showed up
      as, presumably, false-negative on fluorodeoxyglucose-positron emission tomography
      (FDG-PET), while being positive on tyrosine-PET. Neoadjuvant treatment, which
      consisted of combined chemo-radiation and consecutive selective embolization of
      the tumor feeding vessels, caused such a therapeutic effect, on both NICTH and
      reduction in tumor volume, that a secondary resection, with the patient in a
      normoglycemic status, was possible. Our report highlights several important
      issues in the management of the patient with a nonresectable solitary fibrous
      tumor with severe episodes of hypoglycemia due to NICTH.

PMID- 17180520
TI  - Avascular necrosis of bilateral femoral head as a result of long-term steroid
      administration for radiation pneumonitis after tangential irradiation of the
      breast.
AB  - We report a patient with avascular necrosis of the bilateral femoral head
      resulting from long-term steroid administration for radiation pneumonitis that
      occurred after tangential irradiation of the breast. The patient was a 50-year
      old postmenopausal woman with breast cancer, stage IIIB (T4bN0M0) in the right C
      area. Following wide excision of right breast carcinoma and level III axillary
      lymph node dissection, whole-breast X-ray irradiation was given, at a dose of 2
      Gy per fraction; the total dose was 50 Gy. On day 84 after the initiation of
      radiation therapy, she developed radiation pneumonitis. As the lung shadow
      expanded to the contralateral lung, she received steroid medication. Despite the
      steroid medication, the symptoms were exacerbated; therefore, she underwent
      steroid pulse administration with subsequent oral steroid medication. She
      improved immediately, but subsequently the radiation pneumonitis relapsed three
      times when the steroid medication was stopped. The period of medication was 423
      days and the cumulative amount of steroids was 7365 mg before complete resolution
      occurred. In the 19 months after she stopped the steroid administration, she
      developed avascular necrosis (AVN) of the bilateral femoral head. This was
      regarded as a complication of the steroid treatment. Patients treated with long
      term or high-dose steroid administration have been suggested to be at great risk
      of developing AVN, but this hypothesis remains controversial. The probability of
      AVN occurrence may be very small, but it should be considered as one of the
      complications of steroids, which are often used to treat radiation pneumonitis.

PMID- 17180521
TI  - Resistance to gefitinib.
AB  - Subsets of patients with non-small cell lung cancer (NSCLC) who carry somatic
      mutations in the epidermal growth factor receptor (EGFR) have responded
      remarkably well to a tyrosine kinase inhibitor (TKI), gefitinib. Despite the
      dramatic response to this inhibitor, most patients nevertheless ultimately have a
      relapse. We herein report a case of advanced NSCLC in a patient carrying mutated
      EGFR (delE746-A750) who had a relapse after dramatic improvement by gefitinib
      treatment. The DNA sequence of the EGFR gene in a tumor biopsy specimen obtained
      from the relapse site revealed the presence of a second point mutation, resulting
      in a threonine-to-methionine amino acid substitution at position 790 of EGFR,
      which could not be detected in the tumor specimen taken before the treatment.
      Screening subjects with EGFR mutations therefore allows us to identify patients
      who can be successfully treated with gefitinib. Such observations should also
      help us in the search for more effective therapies against a specific subset of
      NSCLC.

PMID- 17180522
TI  - Aqueous humor dynamics associated with the phorbol ester-induced decrease in
      intraocular pressure in the rabbit.
AB  - PURPOSE: To determine the effects of injection of the protein kinase C (PKC)
      activator phorbol 12-myristate 13-acetate (PMA) into the anterior chamber of the
      eye on intraocular pressure (IOP) and aqueous humor dynamics. METHODS: IOP was
      measured for 24 h after intracameral injection of PMA (3 to 50 pmol) in
      unanesthetized rabbits. Aqueous humor dynamics (aqueous flow, total outflow
      facility, and uveoscleral outflow) were determined approximately 6 h after
      injection of 50 pmol of PMA in animals pretreated with indomethacin. RESULTS:
      Intracameral injection of 50 pmol of PMA induced a biphasic effect on IOP,
      consisting of a transient increase apparent at 0.5 and 1 h and a sustained
      decrease apparent after 2 h. This effect of PMA was dose dependent. Whereas
      pretreatment with indomethacin attenuated the PMA-induced increase in IOP, the
      sustained decrease in IOP remained apparent in the pretreated rabbits.
      Intracameral injection of 4alpha-PMA, an inactive PMA analog, had no effect on
      IOP. PMA also significantly increased uveoscleral outflow, but it had no effect
      on aqueous flow or total outflow facility. CONCLUSION: Intracameral injection of
      PMA reduced IOP in the rabbits by increasing the rate of uveoscleral outflow.
      This IOP-lowering effect of PMA may be mediated by activation of PKC.

PMID- 17180523
TI  - Effect and mechanism of betaxolol and timolol on vascular relaxation in isolated
      rabbit ciliary artery.
AB  - PURPOSE: In order to clarify the vasodilatory mechanism of betaxolol and timolol,
      we studied the effects of these drugs in isolated rabbit ciliary arteries.
      METHODS: Rabbit ciliary artery specimens were mounted in a double myograph
      system, and betaxolol, timolol, or another agent was introduced into the organ
      chamber. The mechanical response of the arteries was studied using an isometric
      tension recording method. The intracellular free calcium concentration [Ca2+]i
      was also measured using fluorescence photometry. RESULTS: Betaxolol and timolol
      induced dose-dependent relaxation in the rabbit ciliary arteries precontracted by
      high-K+ Krebs solution. The minimum concentrations required to cause relaxation
      were 10 microM of betaxolol, and 30 microM of timolol. At the maximum
      concentration of 1 mM, betaxolol induced almost complete relaxation of the
      ciliary arteries, whereas timolol induced approximately 70% relaxation. These
      actions were not inhibited by pretreatment with 100 microM NG-nitro-l-arginine
      methylester (L-NAME), a nitric oxide synthase inhibitor, or by denudation of the
      vascular endothelium. However, 300 microM of betaxolol or timolol decreased the
      [Ca2+]i of the vascular smooth muscle, an action similar to that of diltiazem, a
      typical L-type voltage calcium-channel blocker. CONCLUSIONS: Betaxolol, a
      selective beta1-adrenoceptor antagonist, and timolol, a nonselective beta
      adrenoceptor antagonist, both frequently used in the medical management of
      glaucoma, decrease [Ca2+]i by acting as Ca2+ channel blockers, thus causing
      relaxation of isolated rabbit ciliary artery.

PMID- 17180524
TI  - Alteration of leukocyte-endothelial cell interaction during aging in retinal
      microcirculation of hypertensive rats.
AB  - PURPOSE: Hypertension, one of the more common chronic diseases affecting the
      elderly, has been reported to influence leukocyte-endothelial cell interaction.
      The leukocyte-mediated inflammatory process contributes to age-related changes in
      vessels. This study was designed to evaluate age-related changes in leukocyte
      endothelial cell interaction in the hypertensive rat retina. METHODS: Male
      spontaneous hypertensive rats (SHR; 1.5, 3, 6, 12, and 20 months of age) and age
      matched Wistar-Kyoto rats (WKY) were used. The number of accumulated leukocytes
      was counted in sections of flat-mounted retinal tissue. The expression of
      intercellular adhesion molecule-1 (ICAM-1) and CD18 (the common beta-chain of
      ICAM-1 ligands) was evaluated. Retinal thickness was evaluated histologically.
      RESULTS: The number of accumulated leukocytes and the expression of ICAM-1 and
      CD18 increased in the aged retina. The number of leukocytes that accumulated and
      the expression of CD 18 were significantly higher in the SHR group than in the
      WKY group (P < 0.01). In addition, retinal thickness decreased with age.
      CONCLUSION: Leukocyte-endothelial cell interaction increased in the aged retina
      and these changes were more severe in SHR retina than in WKY retina. This
      increased interaction was first observed at 3 months, a relatively young age.

PMID- 17180525
TI  - Vitreoretinal disorders in anterior megalophthalmos.
AB  - PURPOSE: To describe vitreoretinal abnormalities in patients with anterior
      megalophthalmos (AM) and to report the results of vitreoretinal surgery in these
      cases. METHODS: In a retrospective, noncomparative case series, a diagnosis of AM
      was made according to the following criteria: megalocornea, iris hypoplasia, lens
      subluxation, cataract formation at an early age, and absence of congenital
      glaucoma. Vitreous biomicroscopy and funduscopy were performed in all patients.
      Patient records were also reviewed. RESULTS: Twenty-four patients with AM (12
      male, 12 female), aged 4 months to 64 years, were included in this study.
      Funduscopy was possible in 46 eyes. Vitreous degeneration was the most common
      abnormal posterior segment finding, present in 34 eyes (73.9%). Nine eyes (19.5%)
      had optically empty vitreous with strands. Lattice degeneration was seen in five
      eyes (10.8%). Spontaneous vitreous hemorrhage occurred in three eyes, and
      peripheral retinal neovascularization was detected in two. Retinal detachment
      occurred in 18 eyes (37.5%); retinal breaks were detected in eight of these
      before surgery. Thirteen eyes underwent a total of 18 procedures. Retinal
      reattachment was finally achieved in 12 of the 13 eyes. CONCLUSIONS: Anterior
      megalophthalmic eyes seem to be affected by a type of vitreoretinopathy
      predisposing to retinal detachment. Current vitreoretinal surgical techniques
      usually achieve good anatomic results in these cases.

PMID- 17180526
TI  - Verteporfin therapy for neovascular age-related macular degeneration in Indian
      eyes.
AB  - PURPOSE: To determine visual outcome after a 12-month follow-up period of
      verteporfin therapy for subfoveal choroidal neovascularization (CNV) secondary to
      age-related macular degeneration (AMD) in Indian patients. METHODS: Twenty-five
      patients (26 eyes) who completed a 12-month follow-up after photodynamic therapy
      for subfoveal CNV secondary to AMD were included in the study. The follow-up
      schedule was every month for 2 months and then every 3 months thereafter until 12
      months. Improvement in visual acuity was defined as a >or=10-letter gain, and
      deterioration as a >or=10-letter loss in the Early Treatment Diabetic Retinopathy
      Study chart at 4 m. RESULTS: The mean age of the 25 patients was 62.3 +/- 9
      years. There were 17 male patients (68%). The mean initial letter acuity was 28.
      4 +/- 14.1, and the final letter acuity was 25.5 +/- 18.4 at 12 months. Initial
      visual acuity was >or=20/40 in seven eyes, 20/50-20/80 in nine eyes, and 20/100
      20/200 in ten eyes; seven eyes had a >or=10-letter gain, and three eyes had a
      >or=10-letter loss. At the end of 12 months, six eyes had a >or=10-letter gain
      and ten eyes had a >or=10-letter loss. CONCLUSION: Photodynamic therapy appears
      to preserve the vision in subfoveal CNV secondary to AMD in the eyes of Indian
      patients.

PMID- 17180527
TI  - Pars plana vitrectomy with removal of posterior hyaloid face in treatment of
      refractory diabetic macular edema resistant to triamcinolone acetonide.
AB  - BACKGROUND: Triamcinolone acetonide (TA) has recently been used to treat diabetic
      macular edema (DME) but its effectiveness is limited. CASES: Three patients
      (three eyes) with unresolved diffuse DME who did not respond to a posterior sub
      Tenon's injection of TA underwent vitrectomy. OBSERVATIONS: Intraoperatively, it
      was found that all of the eyes had a posterior hyaloid face that was adherent to
      a large area of the posterior pole retina, although this had not been detected by
      slit-lamp biomicroscopy or optical coherence tomography. After vitrectomy and
      removal of the posterior hyaloid face, there was a significant reduction in the
      central macular thickness of all three eyes and an improvement in the visual
      acuity of the patients. CONCLUSIONS: When TA treatment is not effective for DME,
      vitrectomy with the complete removal of the posterior hyaloid face, including
      removal of the internal limiting membrane, should be considered.

PMID- 17180528
TI  - Improvement of scotopic electroretinograms and night blindness with recovery of
      serum zinc levels.
AB  - BACKGROUND: We sought to determine the cause of reduced scotopic and photopic
      electroretinograms (ERGs) and night blindness in a 46-year-old man with liver
      dysfunction but no history of alcoholism. CASE: A 46-year-old Japanese man with a
      complaint of visual difficulties in dim light for 1 month. OBSERVATIONS: By
      electrophysiological investigation, the patient was found to have low levels of
      serum zinc and vitamin A on admission. The rod b wave was unrecordable, and the
      bright-flash ERGs were reduced, with the a wave > b wave. The amplitudes of the
      cone and 30-Hz flicker responses were also reduced, and their implicit times were
      prolonged. Three weeks after admission, the patient's serum zinc level recovered
      to normal levels, but his serum vitamin A level was still low. The symptoms of
      night blindness were gone, and the rod ERGs and single bright-flash responses
      were within normal limits. However, the cone ERGs and 30-Hz flicker responses
      were still depressed. CONCLUSIONS: The recovery of scotopic function together
      with the recovery of zinc but not vitamin A levels suggests that the ERG changes
      were most likely related to low zinc levels.

PMID- 17180530
TI  - Ciliary body schwannoma successfully treated by local resection.
AB  - BACKGROUND: Schwannoma arising from the ciliary body is a rare intraocular
      neoplasm, and most cases previously reported were diagnosed histopathologically
      after eyeball enucleation because of a diagnosis of ciliary body melanoma. CASE:
      A case of ciliary body schwannoma was dissected locally. OBSERVATIONS: A 19-year
      old woman was referred to us with a diagnosis of iris cyst. Local resection of
      the tumor was performed because of deteriorated visual acuity caused by
      displacement of the lens. In histopathological analysis, the encapsulated tumor
      showed a proliferation of the spindle cells with no atypia, and in
      immunohistochemical analysis, tumor cells were positive for S-100 protein; these
      findings were compatible with schwannoma. Visual acuity improved postoperatively,
      and no complications or recurrence have been observed in the 4 years since
      surgery. CONCLUSIONS: Schwannoma should be considered in the differential
      diagnosis of a ciliary body tumor.

PMID- 17180531
TI  - No apparent association between ocular perfusion pressure and visual field damage
      in normal-tension glaucoma patients.
AB  - PURPOSE: To investigate the correlation of ocular perfusion pressure (OPP) with
      general and localized visual field damage in normal-tension glaucoma (NTG)
      patients. METHODS: Correlations between OPP, blood pressure, age, intraocular
      pressure, refractive error, and extent of visual field damage in the eye with the
      worst mean deviation (MD) were investigated retrospectively in 94 eyes of 94 NTG
      patients. Visual fields were analyzed statistically with respect to 15 sectors
      between two age-matched groups of subjects with high or low OPP. RESULTS:
      Significant positive correlations were found between OPP and age (P < 0.001),
      blood pressure and age (P < 0.05), and MD and refractive error (P < 0.01). OPP
      had no significant correlation with MD or mean sensitivity in the visual field in
      any of the visual field sectors. CONCLUSION: OPP and systemic blood pressure have
      no evident effect on the extent or pattern of visual field damage in NTG.

PMID- 17180529
TI  - Early relapse in multiple sclerosis-associated optic neuritis following the use
      of interferon beta-1a in Chinese patients.
AB  - PURPOSE: The incidence of multiple sclerosis (MS) is relatively rare in Chinese.
      The beneficial effect of interferon beta-1a in modifying the disease course of MS
      has been rarely analyzed in Chinese patients. The aim of this study was to
      investigate the clinical response to interferon beta1-a in Chinese patients with
      MS-associated optic neuritis (ON). METHODS: A retrospective case control study
      was conducted in 20 MS patients with optic nerve involvement. The interferon (IF)
      group comprised ten patients receiving interferon beta-1a. The noninterferon
      (NIF) group comprised another ten MS patients with optic nerve involvement who
      did not receive interferon treatment. The clinical characteristics, laboratory
      data, management, and disease course were retrospectively analyzed. The main
      outcomes of the study were the annualized relapse rate (ARR) for MS, and final
      visual outcome data. RESULTS: The ARR did not differ between the pretreatment
      period and the posttreatment period within the IF group. There was also no
      significant decrease of ARR in the IF group when compared with the NIF group.
      However, we observed an early recurrence of ON in 50% of the IF cases following
      the use of interferon beta-1a. The final visual outcome did not differ between
      the IF group and the NIF group. CONCLUSIONS: The use of interferon beta-1a should
      be carefully monitored because early relapse of ON may complicate the treatment
      course in this patient group.

PMID- 17180532
TI  - Surgical excision of retinal macroaneurysms with submacular hemorrhage.
AB  - PURPOSE: To report the visual outcome following the surgical excision of retinal
      macroaneurysms with submacular hemorrhage. METHODS: Two patients presented with
      decreased vision caused by submacular hemorrhage from retinal macroaneurysms. In
      the first case, the macroaneurysm was too large to be treated by
      photocoagulation, and in the second case the direct photocoagulation during the
      first vitrectomy did not prevent the recurrence of hemorrhages. Vitrectomy with
      surgical excision of the retinal macroaneurysm using scissors and diathermy with
      a drainage of the submacular hemorrhage was then performed. RESULTS: In the first
      patient, the visual acuity was light perception before treatment and 2/200 16
      months after the excision. In the second patient, the visual acuity was 20/667
      before treatment and 20/40 11 months after the excision. No hemorrhage has
      recurred in either case after the second vitrectomy. CONCLUSIONS: The surgical
      excision of retinal macroaneurysms might be an effective procedure in cases where
      the macroaneurysm is too large or cannot be treated by photocoagulation during
      vitrectomy.

PMID- 17180533
TI  - Relaxation of encircling buckle improved choroidal blood flow in a patient with
      visual field defect following encircling procedure.
AB  - BACKGROUND: We report a patient with a visual field defect after retinal
      reattachment by the encircling procedure for rhegmatogenous retinal detachment.
      We confirmed improved ocular blood flow after relaxation of the buckle. CASE: A
      24-year-old woman with a visual field defect appearing after an encircling
      procedure for rhegmatogenous retinal detachment. OBSERVATIONS: Before and after
      relaxing the encircling buckle, we measured tissue blood flow in the fundus of
      each eye of the patient using a Heidelberg retina flow meter. Preoperative
      measurements showed a reduction of blood flow at the disc rim in the diseased
      fundus, while retinal blood flow was not reduced (P = 0.026, disc rim area versus
      retinal area, one-factor analysis of variance, ANOVA). Indocyanine green
      angiography showed extensive peripheral filling delay. Electroretinography showed
      low a-wave and b-wave amplitudes, but normal oscillatory potential. The base
      value of the electro-oculogram was severely reduced in the right eye. The blood
      flow values after surgery indicated a significant improvement of blood flow (P =
      0.01, one-factor ANOVA). No further progression in the visual field defect was
      observed, and visual acuity of the right eye improved from 0.8 to more than 1.0.
      CONCLUSIONS: These results suggest that the choroidal circulation disturbance,
      which was found after the encircling procedure, had a plausible role in the
      development of the visual field defect.

PMID- 17180534
TI  - Iris involvement in natural killer/T-cell lymphoma.

PMID- 17180535
TI  - Chronic panuveitis and scleritis in a patient with cryptogenic organizing
      pneumonia.

PMID- 17180536
TI  - Intraocular concentration of intravenous prednisolone in experimental autoimmune
      uveoretinitis mice.

PMID- 17180537
TI  - Frosted branch angiitis-like fundus following presumed influenza virus type A
      infection.

PMID- 17180539
TI  - Foveal retinal detachment and retinoschisis without macular hole associated with
      tilted disc syndrome.

PMID- 17180540
TI  - Visual hallucinations following stellate ganglion block in a patient with central
      retinal artery occlusion.

PMID- 17180538
TI  - Pseudomonas scleral abscess following pars plana vitrectomy.

PMID- 17180541
TI  - Canonical correlation analysis of factors involved in the occurrence of peptic
      ulcers.
AB  - The impact of risk factors on the development of peptic ulcers has been shown to
      vary among different populations. We sought to establish a correlation between
      these factors and their involvement in the occurrence of peptic ulcers for which
      a canonical correlation analysis was applied. We included 7,014 patient records
      (48.6% women, 18.4% duodenal ulcer [DU], 4.6% gastric ulcer [GU]) of those
      underwent upper gastroendoscopy for the last 5 years. The variables measured are
      endoscopic findings (DU, GU, antral gastritis, erosive gastritis, pangastritis,
      pyloric deformity, bulbar deformity, bleeding, atrophy, Barret esophagus and
      gastric polyp) and risk factors (age, gender, Helicobacter pylori infection,
      smoking, alcohol, and nonsteroidal anti-inflammatory drugs [NSAIDs] and aspirin
      intake). We found that DU had significant positive correlation with bulbar
      deformity (P=2.6 x 10(-23)), pyloric deformity (P=2.6 x 10(-23)), gender (P=2.6 x
      10(-23)), H. pylori (P=1.4 x 10(-15)), bleeding (P=6.9 x 10(-15)), smoking (P=1.4
      x 10(-7)), aspirin use (P=1.1 x 10(-4)), alcohol intake (P=7.7 x 10(-4)), and
      NSAIDs (P=.01). GU had a significantly positive correlation with pyloric
      deformity (P=1,6 x 10(-15)), age (P=2.6 x 10(-14)), bleeding (P=3.7 x 10(-8)),
      gender (P=1.3 x 10(-7)), aspirin use (P=1.1 x 10(-6)), bulbar deformity (P=7.4 x
      10(-4)), alcohol intake (P=.03), smoking (P=.04), and Barret esophagus (P=.03).
      The level of significance was much higher in some variables with DU than with GU
      and the correlations with GU in spite of being highly significant the majority,
      were small in magnitude. In conclusion, Turkish patients with the following
      endoscopic findings bulbar deformity and pyloric deformity are high-risk patients
      for peptic ulcers with the risk of the occurrence of DU being higher than that of
      GU. Factors such as H. pylori, smoking, alcohol use, and NSAIDs use (listed in a
      decreasing manner) are risk factors that have significant impact on the
      occurrence of DU; aspirin has a significant impact on both DU and GU.

PMID- 17180542
TI  - Global research on Helicobacter pylori.

PMID- 17180544
TI  - Inguinal herniorrhaphy in women: should the mesh be implanted preperitoneal?

PMID- 17180543
TI  - Necrotizing fasciitis of the abdominal wall with lethal outcome: a case report.
AB  - Necrotizing fasciitis is an acute surgical condition that demands prompt and
      multi-faceted treatment. Early recognition, aggressive surgical debridement, and
      targeted antibiotic therapy significantly affect the overall course of treatment
      and survival. The author reports here the case of a woman with necrotizing
      fasciitis of the abdominal wall and the course and methods of treatment. Two
      comorbidity factors (extreme obesity, diabetes) and the late diagnosis of
      necrotizing fasciitis, the latter masked by celullitis and phlegmona of the
      abdominal wall, resulted in overdue adequate surgical treatment. The combination
      of these factors contributed to medical treatment failure and, consequently, a
      lethal outcome.

PMID- 17180545
TI  - A morphometrical study of the medullary cavity of the ulna referred to
      intramedullary nailing.
AB  - Intramedullary fixation is preferred for osteosynthesis in the case of long bone
      fractures; but the problem of the nails' adjustment to the anatomical needs
      remains. About 80 cadaveric ulnae were examined to elucidate the curvature of the
      medullary cavity, the point of varus angulation, the thickness of the radial and
      ulnar cortical bone and the diameter of the medullary cavity at that point.
      Furthermore, the point of varus angulation of the posterior border was compared
      to that of the medullary cavity, to evaluate if it allows any conclusion to the
      curvature of the medullary cavity. The point of varus angulation of the medullary
      cavity ranged from 45 to 110 mm (mean 71.02), its angle from 4 to 13.5 grade
      (mean 8.95). At this point, the thickness of the cortical bone on the radial side
      was between 2.5 and 7 mm (mean 4.44) and ulnar between 2 and 8 mm (mean 4.37).
      The diameter ranged from 4 to 10.5 mm (mean 6.96). The point of varus angulation
      of the posterior border was between 65 and 110 mm (mean 85.88) and differs from
      that of the medullary cavity observed between 45 and 110 mm (mean 71.02). The
      point of varus angulation of the posterior border and the medullary cavity
      differs from 1 to 60 mm and it is found in most cases to be more distal than the
      point of varus angulation of the medullary cavity so the palpable posterior
      border allows no reliable conclusion of the curvature of the medullary cavity.

PMID- 17180546
TI  - Larger numbers of immature dendritic cells augment an anti-tumor effect against
      established murine melanoma cells.
AB  - The dendritic cell (DC) is a potentially promising tool for cancer immunotherapy.
      To date, however, DC-based immunotherapy has not yielded data with which firm
      conclusions can be drawn. In the present study, we tested the dose-dependant
      enhancement of the anti-tumor effect induced by DCs. When large numbers of DCs
      were used, tumor growth was suppressed up to 41% when compared to control mice.
      Survival of the animals was prolonged to 54 days compared to the 33-day survival
      the control mice. The delayed-type hypersensitivity (DTH) response induced was 26
      fold higher than in the controls. Larger numbers of DCs also led to higher
      expansion of IFN-gamma-secreting-CD8(+) T cells. Furthermore, the secretion of IL
      12p70 and IFN-gamma by spleen cells were enhanced in proportion to the dosage.
      However, the level of IL-4 secreted from spleen cells was negligible compared to
      the level of IFN-gamma that was released. These results indicate that DCs induce
      Th1-dominant immune response and that more DCs could lead to better immunological
      results, a finding which was consistent with our therapeutic results.

PMID- 17180547
TI  - Effects of side-chain orientation on the 13C chemical shifts of antiparallel beta
      sheet model peptides.
AB  - The dependence of the (13)C chemical shift on side-chain orientation was
      investigated at the density functional level for a two-strand antiparallel beta
      sheet model peptide represented by the amino acid sequence Ac-(Ala)(3)-X
      (Ala)(12)-NH(2) where X represents any of the 17 naturally occurring amino acids,
      i.e., not including alanine, glycine and proline. The dihedral angles adopted for
      the backbone were taken from, and fixed at, observed experimental values of an
      antiparallel beta-sheet. We carried out a cluster analysis of the ensembles of
      conformations generated by considering the side-chain dihedral angles for each
      residue X as variables, and use them to compute the (13)C chemical shifts at the
      density functional theory level. It is shown that the adoption of the locally
      dense basis set approach for the quantum chemical calculations enabled us to
      reduce the length of the chemical-shift calculations while maintaining good
      accuracy of the results. For the 17 naturally occurring amino acids in an
      antiparallel beta-sheet, there is (i) good agreement between computed and
      observed (13)C(alpha) and (13)C(beta) chemical shifts, with correlation
      coefficients of 0.95 and 0.99, respectively; (ii) significant variability of the
      computed (13)C(alpha) and (13)C(beta) chemical shifts as a function of chi(1) for
      all amino acid residues except Ser; and (iii) a smaller, although significant,
      dependence of the computed (13)C(alpha) chemical shifts on chi(xi) (with xi > or
      = 2) compared to chi(1) for eleven out of seventeen residues. Our results suggest
      that predicted (13)C(alpha) and (13)C(beta) chemical shifts, based only on
      backbone (phi,psi) dihedral angles from high-resolution X-ray structure data or
      from NMR-derived models, may differ significantly from those observed in solution
      if the dihedral-angle preferences for the side chains are not taken into account.

PMID- 17180548
TI  - Resonance assignment of the RGS domain of human RGS10.

PMID- 17180549
TI  - Separated local field NMR experiments on oriented samples rotating at the magic
      angle.
AB  - Biophysical studies on membrane proteins by solid state NMR (SSNMR) can be
      carried out directly in a membrane environment. Samples are usually prepared in
      form of multi-lamellar dispersions for magic angle sample spinning or as aligned
      multi-layers for orientation dependent NMR experiments without sample rotation. A
      new development is the application of MAS NMR to aligned samples (MAOSS; Magic
      Angle Oriented Sample Spinning). In combination with separated local field (SLF)
      experiments, size and orientation of heteronuclear dipolar couplings may be
      extracted from two-dimensional experiments which correlate dipolar couplings with
      isotropic chemical shifts. The orientation of these (1)H-X dipolar couplings can
      be directly related to the orientation of molecular groups in the sample. Here,
      we demonstrate the feasibility of these experiments on highly ordered
      polyethylene fibers which serve as model compound. Based on these data, the
      experiment is also applied to ordered multi-layers of bacteriorhodopsin (purple
      membrane) which is used as a model for aligned membrane proteins. We present a
      detailed analysis of different experimental designs with respect to angular
      sensitivity and the influence of residual sample disorder ("mosaic spread"). The
      results of the MAOSS-SLF experiment are discussed within the context of
      established solid state NMR experiments which are usually performed without
      sample rotation and we compare the data to orientation information obtained from
      X-ray diffraction.

PMID- 17180550
TI  - 1H, 13C, and 15N chemical shift assignments for the N-terminal extracellular
      domain of T-cadherin.

PMID- 17180552
TI  - The periosteum--a surface for all seasons.

PMID- 17180551
TI  - Observation of microsecond time-scale protein dynamics in the presence of Ln3+
      ions: application to the N-terminal domain of cardiac troponin C.
AB  - The microsecond time-scale motions in the N-terminal domain of cardiac troponin C
      (NcTnC) loaded with lanthanide ions have been investigated by means of a (1)H(N)
      off-resonance spin-lock experiment. The observed relaxation dispersion effects
      strongly increase along the series of NcTnC samples containing La(3+), Ce(3+),
      and Pr(3+) ions. This rise in dispersion effects is due to modulation of long
      range pseudocontact shifts by micros time-scale dynamics. Specifically, the
      motion in the coordination sphere of the lanthanide ion (i.e. in the NcTnC EF
      hand motif) causes modulation of the paramagnetic susceptibility tensor which, in
      turn, causes modulation of pseudocontact shifts. It is also probable that
      opening/closing dynamics, previously identified in Ca(2+)-NcTnC, contributes to
      some of the observed dispersions. On the other hand, it is unlikely that monomer
      dimer exchange in the solution of NcTnC is directly responsible for the
      dispersion effects. Finally, on-off exchange of the lanthanide ion does not seem
      to play any significant role. The amplification of dispersion effects by Ln(3+)
      ions is a potentially useful tool for studies of micros-ms motions in proteins.
      This approach makes it possible to observe the dispersions even when the local
      environment of the reporting spin does not change. This happens, for example,
      when the motion involves a 'rigid' structural unit such as individual alpha
      helix. Even more significantly, the dispersions based on pseudocontact shifts
      offer better chances for structural characterization of the dynamic species. This
      method can be generalized for a large class of applications via the use of
      specially designed lanthanide-binding tags.

PMID- 17180553
TI  - A randomized comparison of transobturator tape and Burch colposuspension in the
      treatment of female stress urinary incontinence.
AB  - This study was performed to compare the efficacy of transobturator tape (TOT) and
      Burch colposuspension in the treatment of female stress urinary incontinence
      (SUI). This is a prospective randomized single blind study of 100 women diagnosed
      as with urodynamic SUI who were randomized either to TOT procedure (n = 49) or
      Burch procedure (n = 51). The outcome was evaluated at 1 and 2 years. The mean
      operation time and hospital stay were significantly shorter in the TOT group
      compared to Burch group (p < 0.001). Procedure-related complications and
      postoperative voiding problems including postoperative urinary retention, de novo
      voiding difficulties and de novo urge incontinence were similar in the two
      groups. Both the subjective and objective cure rates of SUI at 1 year were 85.7
      and 87.5%, respectively, in the TOT group. This was similar to subjective and
      objective cure rates at one year of 84.3% (p = 0.8) and 80.3% (p = 0.4) in the
      Burch group, respectively. At the end of 2 years, 32 patients were available in
      the TOT group and 31 patients were available in the Burch group for analysis.
      Both the subjective and objective cure rates of SUI at 2 years were 87.5 and
      87.5% in the TOT group which was similar to the 87% (p = 0.9) and 83.8% (p = 0.6)
      in the Burch group, respectively. TOT procedure results in similar cure rates of
      SUI at 1 and 2 years compared to Burch procedure. The TOT procedure has a shorter
      operative time and length of hospital stay.

PMID- 17180554
TI  - Posterior retroperitoneoscopic adrenalectomy: a comparison between the initial
      experience in the invention phase and introductory phase of the new surgical
      technique.
AB  - BACKGROUND: Today, the posterior retroperitoneoscopic technique has become a
      standard procedure in adrenal surgery. The procedure allows direct access to the
      adrenal glands, but it seems to be difficult because of the uncommon anatomic
      view. This study compares the learning period of the new procedure of "posterior
      retroperitoneoscopic adrenalectomy" in the primary invention phase and the
      secondary introductory phase in a different hospital 10 years later. MATERIALS
      AND METHODS: The analysis included 100 posterior retroperitoneoscopic
      adrenalectomies (PRA) and involved 50 procedures in each center. Group A
      consisted of 44 patients (14 males, 30 females; age: 48.7 +/- 14.5 years)
      undergoing surgery between 07/1994 and 8/1996 (24 right, 26 left; 8 Cushing
      adenomas, 14 Conn adenomas, 11 pheochromocytomas, 7 nonfunctioning adrenocortical
      adenomas, 10 ACTH-dependent adrenal hyperplasias). Group B consisted of 50
      patients (12 males, 38 females; mean age 59.3 +/- 10.7 years) operated between
      01/2004 and 01/2006 (28 right, 22 left tumors; 5 Cushing adenomas, 12 Conn
      adenomas, 4 pheochromocytomas, 29 nonfunctioning adrenocortical adenomas). All
      PRAs were performed with the patient in the prone position with 3-4 trocars
      placed caudally in the region of the 11th and 12th ribs. In group A, the surgical
      team developed the technique of PRA themselves. Before their first PRA, the
      surgical team of group B was introduced to the technique by the group A surgeons
      and afterwards were supervised continuously. RESULTS: No serious intraoperative
      or postoperative complication occurred in either group. Group A experienced 7
      conversions to open surgery, whereas group B had one conversion and one early
      reoperation due to bleeding (P = 0.03; chi(2)-test). The mean operative time was
      117 +/- 41 minutes versus 83 +/- 35 minutes (group A and B respectively; P <
      0.001; t-test). Estimated blood loss was similar in the two groups (47.2 +/- 46.2
      ml versus 54 +/- 16.3 ml, group A versus B, respectively; P = 0.36; t-test).
      CONCLUSIONS: The study demonstrates the feasibility, safety, and reproducibility
      of the new surgical method of PRA both when it is employed in the early phase of
      invention, as well as when performed by surgeon-learners. After comprehensive
      training, the operative time and conversion rate are dramatically reduced,
      allowing for a short learning period.

PMID- 17180557
TI  - "Management of Simple Cysts of the Pancreas: More Work Required"

PMID- 17180556
TI  - The natural history and traditional management of appendicitis revisited:
      spontaneous resolution and predominance of prehospital perforations imply that a
      correct diagnosis is more important than an early diagnosis.
AB  - BACKGROUND: The principle of early exploration on wide indications in order to
      prevent perforation has been the guiding star for the management of patients with
      suspected appendicitis for over 100 years, dating back to a time when
      appendicitis was a significant cause of mortality. Since then there has been a
      dramatic decrease in mortality due to appendicitis. Emerging evidence calls for a
      new understanding of the natural history of untreated appendicitis. This
      motivates a reappraisal of the fundamental principles for the management of
      patients with suspected appendicitis. METHODS: Analysis of epidemiologic and
      clinical studies that elucidate the natural history of appendicitis, i.e. the
      possibility of spontaneous resolution or the risk of progression to perforation,
      the determinants of the proportion of perforations and mortality, and the
      consequence of in-hospital delay. RESULTS: The results presented in a number of
      studies suggest that spontaneous resolution of appendicitis is common, that
      perforation can seldom be prevented, that the risk of perforation has been
      exaggerated and that in-hospital delay is safe. An alternative understanding of
      the inverse relationship between the proportion of negative explorations and
      perforation and the increasing proportion of perforation with length of time is
      presented, mainly explaining these findings by selection due to spontaneous
      resolution. CONCLUSION: Evidence suggests that spontaneous resolution of
      untreated, non-perforated appendicitis is common and that perforation can rarely
      be prevented and is associated with a lower increase in mortality than was
      previously thought. This motivates a shift in focus from the prevention of
      perforation to the early detection and treatment of advanced appendicitis. In
      order to minimize mortality, morbidity and costs avoidance of negative
      appendectomies is more important then preventing perforation. In patients with an
      equivocal diagnosis where advanced appendicitis is deemed less likely a correct
      diagnosis is more important than a rapid diagnosis. These patients can safely be
      managed by active observation with an improved diagnostic work-up under
      observation, which has consistently shown a low proportion of negative
      appendectomies without an increase in the proportion of perforations or
      morbidity. A high proportion of perforations can be explained by selection due to
      undiagnosed resolving appendicitis. The proportion of perforation is therefore a
      questionable measure of the quality of the management of patients with suspected
      appendicitis and should be used with caution.

PMID- 17180555
TI  - Value of laparoscopic appendectomy in perforated appendicitis.
AB  - BACKGROUND: The purpose of this clinical study was to evaluate the efficacy of
      laparoscopic appendectomy in patients with perforated appendicitis. METHODS: This
      study involved a total of 73 consecutive patients who had undergone appendectomy
      for perforated appendicitis between January 1999 and December 2004. While 39
      patients underwent open appendectomy (OA) during the first 3 years, the remaining
      34 patients underwent laparoscopic appendectomy (LA) during the last 3 years.
      RESULTS: There was no case of LA converted to OA. No significant difference was
      found in the operating time between the two groups. Laparoscopic appendectomy was
      associated with less analgesic use, earlier oral intake restart (LA, 2.6 days;
      OA, 5.1 days), shorter median hospital stay (LA, 11.7 days; OA, 25.8 days), and
      lower rate of wound infections (LA, 8.8%; OA, 43.6%). CONCLUSIONS: These results
      suggest that LA for perforated appendicitis is a safe procedure that may prove to
      have significant clinical advantages over conventional surgery.

PMID- 17180558
TI  - Clinico-pathological characteristics and long-term outcome in patients with
      distant metastases from differentiated thyroid carcinoma.

PMID- 17180559
TI  - The use of latissimus dorsi miniflap for reconstruction following breast
      conserving surgery: experience of a small breast unit in a district hospital.
AB  - BACKGROUND: Immediate reconstruction with autogenous tissue is one of the options
      for reconstruction following breast-conservation surgery for breast cancers in
      major centres with ready availability of appropriate skills. Immediate correction
      of volume deficit by latissimus dorsi miniflap (LDMF) in addition has cosmetic
      appeal by filling the defect without extra skin incision. METHODS: Data was
      collected retrospectively from clinical records of 51 patients who underwent LDMF
      procedures in a district general hospital between June 2000 and December 2004,
      and the results were analysed. Postal questionnaire survey was done to assess the
      level of subjective satisfaction of the cosmetic outcome. RESULTS: Wide local
      excision and axillary-node sampling/clearance along with immediate reconstruction
      with a LDMF (involving a musculo-subcutaneous flap without skin) were performed
      in all patients. Patients' median age was 50 years. Sixty-five percent of the
      tumours were in the upper-outer quadrant, median weight of the specimen was 217.5
      g (31-510 g), median clearance margin was 5 mm (0-15 mm) and median pathological
      size of the tumour was 20 mm (8-60 mm). Four patients required mastectomy later,
      whereas 1 patient had flap necrosis. At a median follow-up of 33 months, there
      has been no recurrence. Eighty-six percent of the patients who responded to the
      postal survey were satisfied with the cosmetic outcome. CONCLUSION: Immediate
      LDMF reconstruction is an acceptable way of correcting deformity after breast
      conservation surgery. We demonstrate by our experience that it is a viable option
      for breast cancer in small district hospitals/ breast units.

PMID- 17180560
TI  - Nerve-identifying inguinal hernia repair: a surgical anatomical study.
AB  - BACKGROUND: Pain syndromes of somatic and neuropathic origin are considered to be
      the main causes of chronic pain after open inguinal hernia repair. Nerve
      identification during open hernia repair is suggested to be associated with less
      postoperative chronic pain. The aim of this study was to define clinically
      relevant surgical anatomical zones facilitating efficient identification of the
      three inguinal nerves during open herniorrhaphy. METHOD: Through dissection of 18
      inguinal areas of embalmed and unembalmed human cadavers, identification zones
      were developed for the inguinal nerves (in particular for the genital branch of
      the genitofemoral nerve). RESULTS: The iliohypogastric nerve was identifiable
      running approximately horizontally and ventrally to the internal oblique muscle
      perforating the external oblique aponeurosis at a mean of 3.8 cm (range 2.5-5.5
      cm) cranially from the external ring. When present, the ilioinguinal nerve was
      identifiable running ventrally and parallel to the spermatic cord, dorsally from
      the aponeurosis of the external oblique muscle. Identification of the genital
      branch of the genitofemoral nerve was more comprehensive. The course of the
      genital branch is laterocaudal at the level of the internal inguinal ring.
      CONCLUSION: Based on the newly defined identification zones, peroperative
      identification of all inguinal nerves is possible. Further research is warranted
      to assess clinical feasibility of these zones and to evaluate the influence of
      (facultative) division, preservation or omittance of the identification of
      inguinal nerves on the incidence of chronic pain.

PMID- 17180561
TI  - Early video-assisted thoracic surgery for primary spontaneous hemopneumothorax.
AB  - INTRODUCTION: Primary spontaneous hemopneumothorax (PSHP) is a rare surgical
      emergency. The aim of this study was to compare the previous strategy of tube
      thoracostomy followed by thoracotomy when complications developed with early
      video-assisted thoracic surgery (VATS) for PSHP. METHODS: Between November 1989
      and May 2005, a total of 24 consecutive patients with PSHP were retrospectively
      reviewed. Before January 2000, there were 13 patients who were subjected to the
      treatment strategy of initial tube thoracostomy and underwent operation if the
      condition deteriorated or later complications occurred (group T). Under this
      strategy, all of these patients later required operations. After January 2000,
      another 11 patients were treated with VATS as soon as their condition stabilized
      after tube thoracostomy and resuscitation (group V). The data for the two groups
      were compared: sex, age, involved side, initial heart rate (HR) and mean blood
      pressure (BP), initial hemoglobin (Hb), preoperative blood loss, operating time,
      amount of blood transfusion, period of chest tube drainage (POD), length of
      hospital stay (LOS), complications, and length of follow-up. RESULTS: The sex,
      age, involved side, and the initial HR, BP, and Hb of the two groups were
      similar. The patients of group V had a significantly longer operating time [group
      V, 111 minutes (mean); group T, 85 minutes, P = 0.002]; less preoperative blood
      loss (group V, 946 ml; group T, 1687 ml, P = 0.003); less blood transfusion
      (group V, 465 ml; group T, 1044 ml, P = 0.002); shorter POD (group V, 4 days;
      group T, 7 days, P = 0.011); and shorter LOS (group V, 5 days; group T, 10 days,
      P = 0.002). No mortality or recurrence was noted in the entire series.
      CONCLUSIONS: Our study suggests that surgery should be undertaken for PSHP as
      soon as possible after the clinical condition has stabilized. Under this
      strategy, VATS is an acceptable approach. It allows a shorter hospital stay and
      is exempt from unnecessary blood transfusion. Later complications, such as
      empyema and impaired lung reexpansion, can also be avoided.

PMID- 17180562
TI  - Intraperitoneal polypropylene mesh hernia repair complicates subsequent abdominal
      surgery.
AB  - BACKGROUND: Prosthetic incisional hernia repair (PIHR) is superior to primary
      closure in preventing hernia recurrence. Serious complications have been
      associated with the use of prosthetic material. Complications of subsequent
      surgical interventions after prior PIHR in relation to its anatomical position
      were the objectives of this study. PATIENTS AND METHODS: Patients who underwent
      subsequent laparotomy/laparoscopy after PIHR between January 1992 and February
      2005 at our institution were evaluated. Intraperitoneal and preperitoneal mesh
      was related to complication rates after subsequent surgical interventions.
      RESULTS: Sixty-six of 335 patients underwent re-laparotomy after PIHR. The
      perioperative course was complicated in 76% (30/39) of procedures with
      intraperitoneal placed grafts compared to 29% (8/27) of interventions with
      preperitoneally positioned meshes (P < 0.001). Small bowel resections were
      necessary in 21% of the intraperitoneal group (8/39) versus 0% in the
      preperitoneal group. Surgical site infection rates were higher in the
      intraperitoneal group (10/39, 26%, versus 1/27, 4%). Enterocutaneous fistula
      formation was rare and occurred in two patients after subsequent laparotomy (5%).
      CONCLUSIONS: Re-laparotomy after PIHR with polypropylene meshes are associated
      with more preoperative and postoperative complications when the mesh is placed
      intraperitoneally. Therefore 0intraperitoneal positioning of polypropylene mesh
      at incisional hernia repair should be avoided if possible.

PMID- 17180563
TI  - Utility of once-daily dose of low-molecular-weight heparin to prevent venous
      thromboembolism in multisystem trauma patients.
AB  - INTRODUCTION: Venous thromboembolism is a preventable cause of death in the
      severely injured patient. Low-molecular-weight heparins (LMWHs) have been
      recommended as effective, safe prophylactic agents. However, LMWH use remains
      controversial in patients at risk for bleeding, those with traumatic brain
      injury, and those undergoing multiple invasive or operative procedures. We
      hypothesized that a protocol utilizing once-daily LMWH prophylaxis in high-risk
      trauma patients, regardless of the need for invasive procedures, is feasible,
      safe, and effective. METHODS: From August 1998 to August 2000, all patients
      admitted to our American College of Surgeons-verified Level I trauma facility
      following injury were evaluated for deep venous thrombosis (DVT) risk and
      prospectively followed. Patients at high risk for DVT, including those with
      stable intracranial injuries, were placed on our institutional protocol and
      prospectively followed. Patients on the protocol received daily injections of the
      LMWH, dalteparin; DVT screening was performed with duplex ultrasonography within
      48 hours of admission and after 7 to 10 days after injury. Regimen compliance,
      bleeding complications, DVT rates, and pulmonary embolus (PE) rates were
      analyzed. RESULTS: During the 2-year study period, 6247 trauma patients were
      admitted; 743 were considered at high risk for DVT. Most of the patients were men
      (72%), with a mean age of 38.7 years (range 15-89 years) and a mean injury
      severity score (ISS) of 19.5. Compliance with the daily regimen was maintained in
      74% of patients. DVT was detected in 3.9% and PE in 0.8%. The wound complications
      rate was 2.7%, and the need for unexplained transfusions was 3%. There were no
      exacerbations of head injury following dalteparin initiation due to bleeding.
      There were 16 patient deaths; none was caused by PE or late hemorrhage.
      CONCLUSIONS: Once-daily dosing of prophylactic LMWH dalteparin is feasible, safe,
      and effective in high-risk trauma patients. Our protocol allows one to "operate
      through" systemic prophylaxis and ensures timely prophylaxis for brain-injured
      and multisystem trauma patients.

PMID- 17180565
TI  - Assessments of anal canal sensitivity in patients with soiling 5 years or more
      after colectomy, mucosal proctectomy, and ileal J pouch-anal anastomosis for
      ulcerative colitis.
AB  - INTRODUCTION: To clarify the significance of anal canal sensitivity contribution
      to soiling in patients after ileal J pouch-anal anastomosis (IPAA) for ulcerative
      colitis (UC), we studied the sensory function of the anal canal. METHODS: Forty
      patients with UC who had undergone IPAA with ileostomy closure at least 60 to 132
      months (mean 103.6 months) previously, and who had no preoperative or
      postoperative complications were recruited. They were divided into two groups:
      group A [n = 26; patients without soiling (16 males, 10 females; ages 15-49
      years, mean 36.6 years)] and group B [n = 14; patients with soiling (10 men, 4
      women; ages 24-56 years, mean 40.9 years)] compared with group C [n = 28; control
      subjects (18 men, 10 women; aged 19-49 years, mean 38.5 years)]. Patients with
      soiling were also divided into three groups (B1, rare soiling; B2, occasional
      soiling; B3, frequent soiling). The anal canal sensitivity threshold was measured
      using an anal canal electrosensitivity test (ACEST). The measurement point of
      anal canal was divided into three parts: lower part [1 cm below the dentate line
      (DL), middle part (just on the DL), and upper part (1 cm above the DL]. A small
      electric current from a constant-current generator was passed between the
      electrodes until the patient felt a sensation often described as tingling or
      pulsing. The threshold of sensitivity was assessed in the upper, middle, and
      lower parts of the anal canal. RESULTS: In patients of group C, recording at the
      middle part of the anal canal showed the best results. The anal canal sensitivity
      threshold of group B was significantly higher than those of groups A and C at the
      upper and middle parts (P < 0.0001, respectively). There were no significant
      differences at the lower part among groups. The anal canal sensitivity threshold
      of subgroup B3 was significantly higher than those of groups B1 or B2 at both the
      upper part (P = 0.0002, P = 0.0038, respectively) and middle part (P = 0.0001, P
      = 0.0480, respectively). There were no significant differences at the lower part
      among groups. CONCLUSIONS: The ACEST shows significantly lower sensitivity in the
      proximal and middle anal canal in IPAA patients with soiling.

PMID- 17180564
TI  - Disturbances in melatonin, cortisol and core body temperature rhythms after major
      surgery.
AB  - BACKGROUND: It has been suggested that circadian rhythm disturbances are present
      after major surgery and that this may play a role in the development of
      postoperative sleep disturbances, fatigue, cognitive dysfunction and
      cardiovascular morbidity. The objective of this study was to examine the profile
      of melatonin, cortisol and core body temperature rhythms before and after major
      surgery. METHODS: Blood samples (melatonin and cortisol) and core body
      temperature readings were collected every hour in the 24-h period prior to
      surgery and the 48 h after surgery from 11 patients undergoing major abdominal
      surgery. All patients had private rooms. Light exposure was controlled and
      monitored. Phase markers [50% dim light melatonin onset (DLMO 50%) and offset
      (DLMOff 50%), cortisol and core body temperature acrophase] for the three
      circadian rhythm profiles were calculated before and after surgery. The
      correlation between the melatonin rhythm and time of surgery, duration of surgery
      and opioid use was examined. RESULTS: A median delay in the onset of melatonin
      was seen on the first postoperative day [median DLMO 50% 22:46 hours (range:
      21:15-01:08 hours) on the preoperative day compared with 23:54 hours (range:
      19:09-02:46 hours) on the first postoperative day; P </= 0.05] . A significant
      positive correlation existed between the duration of surgery and the time of
      melatonin onset (r = 0.67, P </= 0.05) . There was a significantly reduced basal
      secretion of melatonin immediately after surgery, with a subsequent significant
      increase in maximum melatonin values on the second postoperative night. A median
      delay of up to 4 h was seen in the timing of the peak of the temperature rhythm
      on the second postoperative day. Both cortisol secretion and core body
      temperature were increased after surgery and did not return to preoperative
      values in the 48 h of the postoperative study period. No significant correlation
      between opioid dose and the basal or maximum melatonin levels or the time of
      melatonin onset was found. CONCLUSION: We found disturbances in three circadian
      markers after major surgery. The clinical consequences of postoperative circadian
      disturbances should be investigated further in the future.

PMID- 17180566
TI  - Pudendal nerve terminal motor latency in patients with or without soiling 5 years
      or more after low anterior resection for lower rectal cancer.
AB  - BACKGROUND: To clarify the neurological function with respect to external anal
      sphincter (EAS) muscles in patients with or without soiling after low anterior
      resection (LAR) for lower rectal cancer, we examined the terminal motor latency
      in the pudendal motor nerves (PNTML). MATERIALS AND METHODS: Thirty-eight
      patients after LAR for lower rectal cancer were studied electrophysiologically
      and compared with 30 healthy volunteers as controls (19 men and 11 women, aged 44
      to 76 years of age, with a mean age of 65.5 years). Patients after LAR were
      divided into two groups [18 patients with soiling (12 men and 6 women, aged 51 to
      77 years with a mean age of 64.8 years), 20 patients without soiling (13 men and
      7 women, aged 47 to 75 years with a mean age of 62.1 years)]. The mean follow-up
      time from LAR was 67.2 months (range 60-84 months). Bilateral (left-sided and
      right-sided) PNTML tests were performed on all patients in order to measure the
      latency of the response in the bilateral EAS muscle following digitally directed
      transrectal pudendal nerve stimulation. RESULTS: The distance from the anal verge
      to the level of anastomosis in patients with soiling (mean, 2.2 cm) was
      significantly shorter than that in patients without soiling (mean, 4.1 cm) (P <
      0.05). Conduction delay of the bilateral PNTML in patients with soiling was
      longer than that in patients without soiling and normal subjects, significantly
      (P < 0.01, respectively). There was no significant difference between the right
      sided and left-sided PNTML. CONCLUSIONS: These findings support the hypothesis
      that soiling after LAR may be partially caused by damage to the bilateral
      pudendal motor nerves.

PMID- 17180567
TI  - Effects of pyrrolidine dithiocarbamate on healing of colonic anastomoses in the
      cecal ligation and puncture model of intraperitoneal sepsis in rats.
AB  - INTRODUCTION: Pyrrolidine dithiocarbamate (PDTC) is a low-molecular thiol
      antioxidant and potent inhibitor of nuclear factor-kappaB (NF-kappaB) activation.
      In recent animal studies, the delaying effect of intraperitoneal sepsis on
      healing of colonic anastomoses has been demonstrated. In this study, we aimed to
      investigate the effects of PDTC on healing of colonic anastomoses in the presence
      of intraperitoneal sepsis induced by a rodent model of cecal ligation and
      puncture (CLP). METHODS: Anastomosis of the left colon was performed on the day
      following CLP in 30 rats that were divided into three groups: sham-operated
      control (laparotomy and cecal mobilization, group I, n =10), cecal ligation and
      puncture (CLP) (group II, n = 10), PDTC-treated group (100 mg/kg IV before
      construction of the colonic anastomosis) (group III, n = 10). On postoperative
      day 6, all animals were sacrificed, and anastomotic bursting pressures were
      measured in vivo. Tissue samples were obtained for further investigation of
      colonic anastomotic hydroxyproline (HP) contents, perianastomotic myeloperoxidase
      (MPO) activity, and malondialdehyde (MDA) and glutathione (GSH) levels. RESULTS:
      There was a statistically significant increase in the activity of MPO and MDA
      levels in the CLP group (group II) along with a decrease in GSH levels, colonic
      anastomotic HP contents, and bursting pressure values when compared to controls
      (group I). However, PDTC treatment led to a statistically significant increase in
      the tissue HP contents, GSH levels, and colonic anastomotic bursting pressure
      values, along with a decrease in MPO activity and MDA levels in group III (p <
      0.05). CONCLUSIONS: This study showed that PDTC treatment significantly prevented
      the delaying effect of CLP-induced intraperitoneal sepsis on anastomotic healing
      in the colon. Further clinical studies are needed to clarify whether PDTC may be
      a useful therapeutic agent to increase the safety of the anastomosis during
      particular operations where sepsis-induced injury occurs.

PMID- 17180569
TI  - Nuss procedure: pediatric surgical solution for adults with pectus excavatum.
AB  - INTRODUCTION: The aim of the study was to compare results of the Nuss procedure
      in adults and children. METHODS: The data were collected prospectively.
      Antibiotic prophylaxis was used in all patients. Differences were tested
      statistically. RESULTS: A total of 35 adults (28 men; male/female ratio 4:1) with
      a median age of 23 years (range 18 years to 47 years 1 month) were included in
      the study. A previous Welch operation had been performed in one (3%). The median
      operating time was 65 minutes (range 45-105 minutes). Two bars were inserted in
      one patient, and stabilizers were used in all. Pneumothorax occurred in 9 (26%),
      wound abscess in 3 (9%), and bar slips in 5 (14%). The median hospital stay was 7
      days (range 4-10 days). Bars were removed in 14 (40%) patients without
      complications. Follow-up occurred 6 and 12 months after bar removed, at which
      times no recurrence of the pectus and no sternal protrusions were seen. In the
      other part of the study, 141 children and adolescents (105 boys; male/female
      ratio 3:1) with a median age of 13 years (range 4 years 11 months to 17 years 8
      months) were included. A previous Welch operation had been performed in five
      (4%). Two bars were inserted in four, and stabilizers were used in 100 (71%). The
      median operating time was 65 minutes (40-185 minutes). Pneumothorax occurred in
      33 (24%), wound abscess in 1 (0.7%), and bar slips in 18 (13%). The median
      hospital stay was 7 days (range 5-18 days). Bars were removed in 77 (55%) without
      complications. Follow-up occurred 6 and 12 months after bar removed, and the last
      follow-up was eventually planned at the end of growth (age 18). The pectus
      recurred in one patient with Marfan syndrome, and sternal protrusion occurred in
      one. Differences between groups were as follows: a significantly higher
      proportion of adult patients were treated with stabilizers (P < 0.001), and there
      were significantly more wound abscesses in adults (P < 0.001). CONCLUSIONS: The
      Nuss procedure is as effective for correcting pectus excavatum in adults as it is
      in children. However, in adults the bars tended to be less stable, and wound
      abscesses occurred more frequently.

PMID- 17180570
TI  - Which comorbid conditions predict complications after surgery for colorectal
      cancer?
AB  - BACKGROUND: Accurate presurgical assessment is important to anticipate
      postoperative complications, especially in the growing proportion of elderly
      cancer patients. We designed a study to define which comorbid conditions at the
      time of diagnosis predict complications after surgery for colorectal cancer.
      PATIENTS: A random sample of 431 patients recorded in the population-based
      Eindhoven Cancer Registry who underwent resection for stage I-III colorectal
      cancer, newly diagnosed between 1995 and 1999 were entered into this study.
      METHODS: The influence of specific comorbid conditions on the incidence and type
      of complications after surgery for colorectal cancer was analyzed. RESULTS:
      Overall, patients with comorbidity did not develop more surgical complications.
      However, patients with a tumor located in the colon who suffered from concomitant
      chronic obstructive pulmonary disease (COPD) more often developed pneumonia (18%
      versus 2%; P = 0.0002) and hemorrhage (9% versus 1%; P = 0.02). Patients with
      colon cancer who suffered from deep vein thrombosis (DVT) at the time of cancer
      diagnosis more often had surgical complications (67% versus 30%; P = 0.04),
      especially more minor infections (44% versus 11%; P = 0.002) and major infections
      (56% versus 10%; P < 0.0001), pneumonia (22% versus 2%; P = 0.01), and
      thromboembolic complications (11% versus 3%; P = 0.02). Patients with a tumor
      located in the rectum who suffered from COPD more frequently had any surgical
      complication (73% versus 46%; P = 0.04), and the presence of DVT at the time of
      cancer diagnosis was predictive of thromboembolic complications (17% versus 4%; P
      = 0.045). The presence of DVT remained significant after adjustment for relevant
      patient and tumor characteristics (odds ratio 9.0, 95% confidence interval 1.1
      27.9). CONCLUSIONS: Among patients undergoing surgery for colorectal cancer,
      development of complications was especially predicted by presence of COPD and
      DVT. In patients with the latter comorbidity, regulation of the pre- and
      postsurgical hemostatic balance needs full attention.

PMID- 17180568
TI  - Improving outcomes in hernia repair by the use of light meshes--a comparison of
      different implant constructions based on a critical appraisal of the literature.
AB  - BACKGROUND: Despite convincing advantages offered by meshes, their use in hernia
      surgery remains controversial because of fears concerning the long-term effects
      of their implantation. To improve biocompatibility, a large variety of newly
      developed light meshes has been introduced to the market. This overview of the
      literature aimed to establish whether absolute material reduction (g per
      implanted mesh), use of absorbable components, and coating by inert materials are
      evidence-based ways to improve biocompatibility of meshes. METHOD: A review of
      the current English and German language literature on the outcome of groin und
      incisional hernia mesh repair was performed. Both basic research and clinical
      trials were used as sources of data. Meta-analyses and randomized controlled
      trials were given priority and were referred to whenever possible. RESULTS:
      Operative technique was an independent prognostic factor for the clinical
      outcome. Mesh construction and composition as characterized by pore size and
      filament structure appeared to be more important determinants of foreign body
      reaction after implantation than absolute material reduction of 1 g or more per
      implant. No data exist about an oncogenic effect of alloplastic materials in
      humans, but disturbed fertility in animal studies remains an issue of concern and
      should be further investigated. CONCLUSIONS: According to data from current
      randomized controlled trials and retrospective studies, light meshes seem to have
      some advantages with respect to postoperative pain and foreign body sensation.
      However, their use is associated with increased recurrence rates. Light meshes
      offer no advantages with respect to alleviating severe chronic groin pain. At the
      same time, experimental data reveal that material composition and mesh structure
      may significantly affect foreign body reaction.

PMID- 17180571
TI  - Volumetric analysis of septal region in schizophrenia and affective disorder.
AB  - MRI and post-mortem studies indicate an increased prevalence of cavum septi
      pellucidi (CSP) in schizophrenia and affective disorder. The aim of this study
      was to characterize the CSP and the septal tissue among patients with
      schizophrenia, patients with affective disorder, and control subjects. The
      volumes of CSP and septal tissue were measured in post-mortem brains in 42
      patients with schizophrenia, 14 patients with affective disorder, and 17 normal
      control cases by planimetry of serial sections. Enlargements of CSP (>100 mm(3))
      were found in eight of the 42 (19%) patients with schizophrenia. There were no
      significant differences in CSP volumes between patients with affective disorder
      and controls. Enlarged CSP in schizophrenia were not associated with reduced
      septal tissue volumes. By contrast, a significant positive correlation between
      volumes of CSP and septal tissue volumes in patients with schizophrenia (P =
      0.03) and in control cases (P < 0.01) was found, but not in patients with
      affective disorder (P = 0.53). The finding of enlarged CSP in schizophrenia
      strongly supports the hypothesis of an early developmental abnormality in this
      key structure of the limbic system.

PMID- 17180572
TI  - A randomized controlled trial comparing hydration therapy to additional
      hemodialysis or N-acetylcysteine for the prevention of contrast medium-induced
      nephropathy: the Dialysis-versus-Diuresis (DVD) Trial.
AB  - Contrast medium-induced nephropathy (CIN) is a serious complication with
      increasing frequency and an unfavorable prognosis. Previous analyses of surrogate
      parameters have suggested beneficial effects of hemodialysis that are assessed in
      this randomized clinical trial. We performed a prospective single-center trial in
      424 consecutive patients with serum creatinine concentrations between 1.3- 3.5
      mg/dl who underwent elective coronary angiography. Patients were randomized to
      one of three treatment strategies with all patients receiving pre- and
      postprocedural hydration: One group received no additional therapy, patients in
      the second group were hemodialyzed once, and the third group received oral N
      acetylcysteine. The frequency of CIN (defined as an increase in serum
      creatinine>or=0.5 mg/dl) from 48 to 72 h after catheterization was 6.1% in the
      hydration-only group, 15.9% with hemodialysis treatment, and 5.3% in the N-ACC
      group (intention-to-treat analysis; P=0.008). There were no differences between
      the treatment groups with regard to increased (>or=0.5 mg/dl) serum creatinine
      concentrations after 30-60 days (4.8%, 5.1%, and 3.1%, respectively; P=0.700).
      Analyses of long-term follow-up (range 63 to 1316 days) by Cox regressions models
      of the study groups found quite similar survival rates (P=0.500). In contrast to
      other (retrospective) studies, long-term survival of patients with vs those
      without CIN within 72 h was not different, but patients who still had elevated
      creatinine concentrations at 30-60 days suffered from a markedly higher 2-year
      mortality (46% vs 17%, P=0.002). In conclusion, hemodialysis in addition to
      hydration therapy for the prevention of CIN provided no evidence for any outcome
      benefit but evidence for probable harm. Increased creatinine concentrations at 30
      60 days, but not within 72 h, were associated with markedly reduced long-term
      survival.

PMID- 17180574
TI  - Recurrent pericarditis in children: elevated cardiac autoantibodies.
AB  - Recurrent pericarditis is a rare disease in childhood. Nevertheless, it may
      represent a challenge to the clinician due to its resistance to anti-inflammatory
      treatment. The initial etiology often remains unclear; specific laboratory
      parameters predicting the frequency or severity of the recurrences are lacking.
      We report on four patients with recurrent pericarditis in whom antimyolemmal
      antibodies (AMLAs) were detected. A prolonged persistence of IgM-type AMLAs was
      found in three patients: two of them presented with acute inflammation as the
      initial event and one with 48 recurrences during 5.5 years. The fourth patient
      showed a fast conversion from IgM to IgG-type AMLAs after a less acute initial
      presentation and showed 4 mild recurrences during the 48-month follow-up.
      CONCLUSION: We were able to detect AMLAs in four children with recurrent
      pericarditis. This finding may be attributed to an auto-immunological disease
      following a first, acute event. We propose the detection of AMLAs in all children
      with unexplained recurrent pericarditis. Pediatric patients with a persistence of
      IgM-type AMLAs may face frequent recurrences and should be monitored therefore
      more closely. In addition, medical treatment may be changed in these patients
      with a slower tapering of the dosage of steroidal and non-steroidal
      antiinflammatory drugs.

PMID- 17180573
TI  - Pathology, natural history and treatment of abdominal aortic aneurysms.
AB  - With increasing age of the population and improvement of diagnostic tools, the
      incidence of abdominal aortic aneurysms (AAA) has been rising steadily. Despite
      an improvement in operative and interventional treatment options, AAA is the
      cause of death in 1-3% of men over 65 years of age in industrial countries,
      mostly due to rupture [1]. Therefore, routine screening for AAA by
      ultrasonography has been postulated in the past: a 60 year old man with an
      abdominal aortic diameter of less than 3 cm has a life-time risk of developing
      AAA close to zero. However, routine screening has not been found to be cost
      effective. Despite of the results of two well-designed studies, the limits of AAA
      qualifying the patient for surgery or intervention in contrast to conservative
      treatment is still a matter of debate. The present review article summarizes the
      current knowledge of the pathology, incidence, risks, natural course as well as
      symptoms and current treatment strategies of AAA on the basis of the recent
      literature.

PMID- 17180575
TI  - Pulmonary and caval blood flow patterns in patients with intracardiac and
      extracardiac Fontan: a magnetic resonance study.
AB  - AIMS: We compared in vivo blood flow and pulsatility after different types of
      Fontan operation using magnetic resonance imaging. MATERIAL AND METHODS: A total
      of 37 consecutive patients (mean age 19+/-7.9 years, 7.3+/-3.2 years after Fontan
      operation), 7 with atriopulmonary anastomosis (APC), 18 with intra-atrial lateral
      tunnel (LTFO) and 12 with extracardiac Fontan (ECFO) were studied using magnetic
      resonance phase-contrast velocity mapping. Blood flow (volume flow) in the
      superior vena cava (SVC), inferior vena cava (IVC) and both pulmonary arteries
      were measured and a pulsatility index was calculated for each vessel. RESULTS:
      For all modifications, the blood flow distribution between the SVC and IVC was
      normal (1:2). Patients with APC had a normal pulsatility, a dilated right atrium,
      partial backward flow in the IVC and physiological blood flow distribution
      between the pulmonary arteries. LTFO and ECFO patients had no retrograde flow in
      the IVC, equal blood flow distribution between the pulmonary arteries and very
      low or absent pulsatility. CONCLUSIONS: MRI allows hemodynamic quantification and
      characterization of various types of Fontan modifications and may be a valuable
      tool to predict Fontan failure. Despite showing normal pulsatility, patients with
      APC have right atrial dilatation and partial backward flow in the IVC,
      demonstrating suboptimal Fontan circulation. LTFO and ECFO both produce
      unidirectional antegrade flow in the IVC but pulsatility is very low or absent,
      which may promote poor pulmonary artery growth and increase of pulmonary vascular
      resistance contributing to late Fontan failure.

PMID- 17180576
TI  - Effect of stress-induced reversible ischemia on serum concentrations of ischemia
      modified albumin, natriuretic peptides and placental growth factor.
AB  - OBJECTIVE: There is controversy whether new biomarkers are able to identify
      myocardial ischemia in the absence of myonecrosis. METHOD: We measured NT-pro
      BNP, NT-pro ANP, ischemia-modified albumin (IMA) and placental growth factor
      (PlGF) in patients undergoing nuclear stress testing for suspected ischemic heart
      disease. A thallium scan was used for detection of reversible myocardial ischemia
      and cardiac troponin T (cTnT) for exclusion of stress-induced myonecrosis. Of 195
      patients, 24 with reversible and 62 with no perfusion defect were included in the
      analysis. Plasma levels were measured before, 18 min and 4 h after stress
      testing. RESULTS: Of the 86 patients, 52 received an exercise stress and 34
      dipyridamol. New myonecrosis indicated by cTnT could be excluded in all patients.
      Plasma levels of NT-pro BNP and NT-pro ANP before testing were significantly
      higher in patients who later developed reversible perfusion defects (NT-pro BNP
      139.00 (58.25/367.01) pg/mL vs 327.45 (120.50/972.85) pg/mL, p<0.05; NT-pro ANP
      732.5 (470.0/1220.0) pg/mL vs 1470.0 (694.0/1910.0) pg/mL, p<0.05). Plasma levels
      of NT-pro BNP, NT-pro ANP and PIGF did not change significantly after stress
      testing, IMA levels rose significantly after 4 h in patients with and without
      reversible perfusion defects. CONCLUSION: The elevation of NTpro BNP and NT-pro
      ANP at baseline may represent the cumulative effect of repeated bouts of
      myocardial ischemia. A single brief episode of provoked ischemia does not cause a
      significant increase of the measured biomarkers beside from IMA after exercise
      stress test potentially indicating skeletal muscle ischemia.

PMID- 17180578
TI  - Glucocorticoid-induced alternative promoter usage for a novel 5' variant of
      granzyme A.
AB  - Glucocorticoids exert diverse physiological functions through transcriptional
      regulation of genes including granzyme A (GZMA). GZMA is one of the apoptotic
      effectors localized in cytotoxic T lymphocytes and is considered to mediate
      glucocorticoid-induced apoptosis of human leukemia 697 cells. In the present
      study, we identified a novel 5' variant transcript of GZMA in dexamethasone (DEX)
      treated 697 cells. We designated this novel transcript as GZMAbeta. The
      transcription of GZMAbeta starts at 290 bp downstream of the first intronic
      glucocorticoid response element (GRE). Chromatin immunoprecipitation assay showed
      that glucocorticoid receptor (GR) binds to the intronic GRE in a DEX-dependent
      manner. Luciferase assay and RT-PCR also showed that DEX induces GZMAbeta
      transcription mediated by GR binding to the intronic GRE. Our results show that
      there exist at least two transcripts in human GZMA, whose expression is
      differentially regulated by glucocorticoid.

PMID- 17180577
TI  - Is late stent thrombosis in drug-eluting stents a real clinical issue? A single
      center experience and review of the literature.
AB  - BACKGROUND: Randomized studies have not found an increased rate of late stent
      thrombosis (LAST) in drug-eluting stents (DES) compared with bare metal stents
      (BMS) but those studies were statistically not powered to show such a difference.
      At the same time there is an increasing number of reports of LAST in DES patients
      in the current literature. PATIENTS AND METHODS: We tried to describe the
      incidence of LAST in an unselected DES and BMS patient population. All patients
      who underwent stenting in our hospital between October 2003 and March 2006 were
      included in the study (n=1377). A total of 424 (30.1%) patients were treated with
      only BMS stents, 520 (37.8%) with paclitaxel-eluting stents (PES), 384 (27.9%)
      with sirolimus-eluting stents (SES) and 49 (3.6%) with BMS and DES. Long-term
      follow-up of all patients was used to determine the incidence of LAST as defined
      by angiographically proven stent thrombosis associated with acute symptoms more
      than 30 days after stent implantation. Followup was between 1 month and 2 years 7
      months (mean 12 months). Patients treated with DES were younger (66+/-11 years)
      than BMS patients (72+/-10 years; p<0.001) and more often had diabetes (24.2% vs
      17.4%; p < 0.001). A previous PCI had been performed in 27.1% of DES patients vs
      13.9% of BMS patients (p < 0.001). RESULTS: There were 9 cases of LAST: 2 with
      SES (at 6 and 11 months after implantation), 6 with PES (at 6, 9 (2x), 10, 16 and
      26 months), and one with BMS (at 22 months). All patients with LAST presented
      with STEMI and without an angina history that suggested restenosis. Two cases
      were related to complete cessation of antiplatelet therapy, one because of
      patient non-compliance (SES), one after aspirin was stopped for orthopedic
      surgery (BMS). Two cases occurred within 1 month of cessation of clopidogrel
      therapy and while these patients were on aspirin therapy. Five cases occurred on
      aspirin monotherapy 2, 3, 4, 10 and 20 months, respectively after planned
      cessation of clopidogrel. None of the cases occurred under dual antiplatelet
      therapy. All patients underwent primary PCI; none died. CONCLUSION:
      Angiographically proven LAST occurred in our unselected patient population with
      an incidence of 0.84% in patients treated with DES and 0.21% in BMS patients
      within a mean follow-up of 12 months (p = 0.36). LAST may indeed occur in
      clinically stable patients while on aspirin monotherapy. Since LAST led in all
      patients to STEMI it seems to be a serious clinical issue that prompts further
      investigation and discussion of length of dual platelet therapy.

PMID- 17180579
TI  - Genetic polymorphisms associated with adverse events and elimination of
      methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma.
AB  - Methotrexate is administered in high doses to treat childhood acute lymphoblastic
      leukemia and malignant lymphoma. Hepatotoxicity and bone marrow suppression often
      limit its use, however. The objective of this study was to determine the genetic
      polymorphisms associated with the hepatotoxicity and elimination of methotrexate.
      Genetic polymorphisms of glutathione S-transferase (GST) genes including GSTT1
      positive/null, GSTM1 positive/null, and GSTP1 A313G, and genes for reduced folate
      carrier 1 G80A (RFC1 G80A), methylenetetrahydrofolate reductase C677T (MTHFR
      C677T), and breast cancer resistant protein C421A (BCRP C421A) were determined
      for 26 patients by the polymerase chain reaction (PCR) method or by direct
      sequencing. A high frequency of hepatotoxicity (P = 0.035) was observed for
      patients with GSTM1 positive and RFC1 AA(80), and serum concentrations of
      methotrexate 48 h after the start of infusion were higher for patients with the
      TT(677) genotype of MTHFR (P = 0.028). In conclusion, GSTM1 positive/null and
      RFC1 G80A polymorphisms could be predictors for hepatotoxicity, and the MTHFR
      C677T polymorphism is associated with elimination of methotrexate.

PMID- 17180580
TI  - Haplotype analysis at the alcohol dehydrogenase gene region in New Zealand Maori.
AB  - Alcohol response is a genetically influenced trait, and there is significant
      variation in the patterns of alcohol consumption between Maori and Caucasians in
      New Zealand. Previous studies have found that a variant of the alcohol
      dehydrogenase (ADH) gene (ADH1B*47His) is associated with protection against
      alcohol dependence in Maori. Here we extend our investigation of the ADH genes,
      hypothesising a different haplotype signature in Maori compared to Caucasians. We
      analysed nine single nucleotide polymorphisms (SNPs) spanning a 500-kb region on
      chromosome 4q surrounding the ADH1B variant and several other alcohol
      metabolising genes (ADH 4, 5, 6, 7). Genotyping was carried out on 47 unrelated
      Maori individuals, and allele frequencies were compared to the Caucasian
      population. Large differences in minor allele frequencies were observed between
      Maori and Caucasian populations for six SNPs (P < 0.01). There was also strong
      linkage disequilibrium (LD) observed among SNP alleles in Maori indicating the
      presence of extended ancestral haplotype blocks (P < 0.01). Our results suggest
      that the Maori population has a different haplotype signature at the ADH gene
      region compared to Caucasians. These findings probably reflect the unique gene
      flow history of this genomic region in Maori and should be beneficial for
      designing future genetic association studies of alcohol-response traits and
      associated disorders in Polynesians.

PMID- 17180581
TI  - Antibiotic treatment of diseases without an evident infectious etiology.

PMID- 17180582
TI  - ECDC's growing responsibilities in defending Europe against infectious diseases.

PMID- 17180583
TI  - Surveillance of antimicrobial use and antimicrobial resistance in German
      intensive care units (SARI): a summary of the data from 2001 through 2004.
AB  - OBJECTIVE: To report the experience gained over 4 years in working with the
      German SARI project (Surveillance of Antimicrobial Use and Antimicrobial
      Resistance in Intensive Care Units), and to compare SARI with data from the
      Swedish STRAMA and the US AUR surveillance system. METHODS: Prospective unit and
      laboratory based surveillance was carried out in 40 German ICUs from 2001 through
      2004. WHO 2004 definitions of defined daily doses (DDD) per 1,000 patient days
      (pd) were used to express antimicrobial consumption (AD). Apart from the
      proportion of resistant isolates (RP), the incidence density of resistant
      isolates (RD) was calculated on the basis of the number of resistant isolates per
      1,000 pd. To determine the changes over time, the Wilcoxon signed rank test for
      paired samples was used. RESULTS: From 1/2001 through 12/2004, 40 ICUs provided
      data on 53,399 isolates, a total of 789,569 DDD and 597,592 pd. Total AD ranged
      from 427 to 2,798, with the median being 1,351. There was no statistically
      significant change in total antimicrobial use, but a statistically significant
      decrease was observed in the use of aminoglycosides. RD was highest for MRSA with
      4.4 resistant isolates/1,000 pd followed by imipenem resistant Pseudomonas
      aeruginosa with 1.7 resistant isolates/1,000 pd. The corresponding RPs were 21.5%
      and 23.2%. Over the 4-year period (2001-2004), significant increases were seen in
      the RDs of third generation cephalosporin and ciprofloxacin resistant Escherichia
      coli. In 2004, the mean RD reached 0.28 and 1.41, respectively. In comparison,
      the RP of selected pathogens was highest in the US ICUs and lowest in Swedish
      ICUs, with the exception of imipenem resistant P. aeruginosa. CONCLUSION:
      Antibiotic consumption remained stable over a period of 4 years, (the mean being
      1,321 DDD/1,000 pd). The same applied to the situation regarding resistance in
      Staphylococcus aureus, enterococci and P. aeruginosa. For most pathogens the RP
      was higher in SARI ICUs than in Swedish ICUs, but lower than in US ICUs.

PMID- 17180584
TI  - Incidence of surgical site infections in general surgery in Italy.
AB  - BACKGROUND: Epidemiological study to determine surgical site infection (SSI)
      rates in surgical patients in Italy using the National Nosocomial Infections
      Surveillance system (NNIS), to monitor current surgical antimicrobial
      prophylaxis, and to identify possible modifiable risk factors for SSI. MATERIALS
      AND METHODS: Thirty-two general surgeries participated in the study. Main
      criteria for site inclusion were: > 20 operations per week and
      amoxycillin/clavulanate among prophylactic options. Each patient operated from
      April 1st to May 30th 2002 was surveyed until 30 days after the operation. SSI
      cumulative incidence rates and 95% confidence intervals (95%CI) were calculated.
      RESULTS: During the study period, 3,066 surgical procedures were performed in
      2,972 patients. A total of 158 SSI were diagnosed in 154 patients: 96 (62.3%)
      were at superficial incision, 23 (14.9%) were at deep incision and 35 (22.7%)
      were at organ-space site. Incidence of SSI every 100 operations was 5.2% (95% CI
      4.4-6.0). Of the 2,437 operated patients with clean or elective
      clean/contaminated or contaminated surgical procedure, 2,105 (86.4%) received
      antimicrobial prophylaxis, mainly amoxicillin/clavulanate (28.3%) and ceftizoxime
      (11.4%). Pre-operative hospital stay > or = 48 h, diabetes, obesity, and HIV/AIDS
      infection were statistically significantly associated with increased risk of SSI.
      CONCLUSIONS: The SSI rates found are comparable with European studies and can be
      a benchmark for national incidence data and for inter- and intra-hospital SSI
      rate comparisons.

PMID- 17180585
TI  - Morganella morganii infections in a general tertiary hospital.
AB  - BACKGROUND: Morganella morganii is a commensal Gram-negative bacillus of the
      intestinal tract of humans and other mammals and reptiles. Few reports exist in
      the literature regarding infections caused by this organism. METHODS: A
      retrospective study at the 650-bed University Hospital of Heraklion, Crete,
      Greece was performed during a 4-year period (2001-2004) to identify and analyze
      infections caused by M. morganii. RESULTS: Twenty-four patients had M. morganii
      isolated from clinical specimens during the study period. Thirteen patients (54%)
      suffered from skin and soft tissue infections, five from pyelonephritis, three
      from female genital tract infections, one from pneumonia, one from gangrenous
      appendicitis, and one from tonsillitis. M. morganii was a constituent of
      polymicrobial infections in 14 patients (58%). The patients received various
      antibiotics, i.e., six patients received ciprofloxacin, four
      piperacillin/tazobactam, two amoxicillin/clavulanic acid, one
      ticarcillin/clavulanic acid, one ceftriaxone, one imipenem, and one cefuroxime
      monotherapy, whereas the remaining eight received antibiotic combinations. Two
      (both debilitated) of 24 patients (8%) died, despite antibiotic treatment.
      CONCLUSION: Skin and soft tissue infection was the commonest type of infection
      due to M. morganii in our series. M. morganii is commonly a part of polymicrobial
      infections and can rarely cause fatalities in debilitated patients.

PMID- 17180586
TI  - Comparison of risk factors for candidemia versus bacteremia in hospitalized
      patients.
AB  - BACKGROUND: Classic risk factors for candidemia include use of total parenteral
      nutrition (TPN), hospital location, use of central venous catheter, and others.
      Unfortunately, most of these variables are now also risk factors for antibiotic
      resistant bacteria. Thus, use of these risk factors to identify patients at high
      risk for candidemia is difficult. The purpose of this study was to compare these
      classic risk factors for candidemia in patients with bloodstream infections to
      determine the relative strength of these predictors in differentiating patients
      with candidemia and bacteremia. METHODS: Clinical data were collected from the
      medical charts of patients who had been hospitalized between 2002 and 2004.
      Patients with their first episode of candidemia or bacteremia during their
      hospital stays were included. Risk factors were assessed using a multivariate
      logistic regression model and internally validated using a bootstrap analysis. A
      p-value < 0.05 was considered significant. RESULTS: A total of 164 patients (82
      with candidemia) were evaluated. According to the logistic analysis, patients who
      had stayed in the intensive care unit (ICU) (OR = 6.24; 95% CI: 2.58-15.09) or
      had been using TPN (OR = 4.69; 95% CI: 1.76-12.48) were more likely to have
      candidemia than bacteremia. While patients with pulmonary (OR = 0.15; 95% CI:
      0.055-0.39) or cardiac disease (OR = 0.21; 95% CI: 0.086-0.51) had a greater
      chance to have bacteremia than candidemia (p < 0.01 for all variables). These
      results were further validated using bootstrap analysis. CONCLUSION: Among
      classic risk factors for candidemia, the ICU location at the time of culture and
      TPN use were most predictive of candidemia while certain medical disorders
      predicted patients at the highest risk for bacteremia. These results can be used
      to help identify patients most likely to benefit from empiric antifungal therapy.

PMID- 17180587
TI  - Safety profile of concomitant use of caspofungin and cyclosporine or tacrolimus
      in liver transplant patients.
AB  - BACKGROUND: Caspofungin is the first substance of a new class of antifungal
      agents, the echinocandins that interfere with fungal cell wall synthesis by
      inhibition of glucan synthesis. Alanine aminotransferase (ALT) elevations were
      seen in phase I studies of patients receiving caspofungin and cyclosporine A
      (CyA). Actually, there is no information regarding hepatotoxicity in liver
      transplant patients treated concomitantly with caspofungin and immunosuppressant
      agents like CyA or tacrolimus (TAC). PATIENTS AND METHODS: We conducted a
      retrospective study in 12 liver transplant patients (9 patients Child C, 3
      patients acute liver failure) to assess the hepatic safety of simultaneous
      administration of caspofungin with CyA or TAC. Caspofungin was administered as
      first-line agent to patients for a 2-week period with either proofed invasive
      fungal infection (IFI) (n = 4), IFI-probable (n = 4), and IFI-possible (n = 4).
      All patients received concomitantly CyA or TAC as immunosuppressant agent.
      RESULTS: Two patients died within the first 10 days after start of treatment,
      caused by gram-negative rods. All other ten patients completed the 14-day
      treatment period. No liver enzyme elevation was recorded in these patients and
      administration of caspofungin with CyA or TAC was well tolerated without
      hepatotoxicity. CONCLUSION: The concomitant use of caspofungin with CyA or TAC in
      liver transplant patients is safe and seemed to be without hepatotoxic effect.

PMID- 17180588
TI  - Primary invasive aspergillosis of the digestive tract: report of two cases and
      review of the literature.
AB  - BACKGROUND: Disseminated aspergillosis is thought to occur as a result of
      vascular invasion from the lungs with subsequent bloodstream dissemination, and
      portals of entry other than sinuses and/or the respiratory tract remain
      speculative. METHODS: We report two cases of primary aspergillosis in the
      digestive tract and present a detailed review of eight of the 23 previously
      published cases for which detailed data are available. RESULTS AND CONCLUSION:
      These ten cases presented with symptoms suggestive of typhlitis, with further
      peritonitis requiring laparotomy and small bowel segmental resection. All cases
      were characterized by the absence of pulmonary disease at the time of
      histologically-confirmed gastrointestinal involvement with vascular invasion by
      branched Aspergillus hyphae. These cases suggest that the digestive tract may
      represent a portal of entry for Aspergillus species in immunocompromised
      patients.

PMID- 17180589
TI  - Antimicrobial resistance of community-acquired bloodstream isolates of viridans
      group streptococci.
AB  - Infections due to antimicrobial-resistant viridans group streptococci are
      increasing. The present study was done to determine the frequency of antibiotic
      resistance among community-acquired viridans group streptococci isolated from
      blood cultures and to identify the risk factors associated with acquiring
      antibiotic-resistant viridans group streptococci. Twenty-eight community-acquired
      viridans group streptococcal isolates were recovered from 27 patients, of which
      89%, 86%, 79%, 61%, and 39% were susceptible to ceftriaxone, clindamycin,
      tetracycline, penicillin, and erythromycin, respectively; 100% were susceptible
      to levofloxacin and vancomycin. Among the patients with previous antibiotic use,
      73% had penicillin non-susceptible viridans group streptococci, compared with 18%
      who did not receive prior antibiotics (p = 0.006). Patients with and without
      prior antibiotic use, 27% and 0%, respectively, had ceftriaxone non-susceptible
      viridans group streptococci isolates, respectively (p = 0.05). Patients with and
      without prior antibiotic use, 45% and 6%, respectively, had tetracycline non
      susceptible viridans group streptococci isolates, respectively (p = 0.02). No
      other risk factors for isolation of non-susceptible viridans group streptococci
      were identified.

PMID- 17180590
TI  - Long-term antibiotic treatment with roxithromycin in patients with multiple
      sclerosis.
AB  - BACKGROUND: There are conflicting results concerning an association between
      Chlamydia pneumoniae and MS (multiple sclerosis). In the present study, we
      investigated a possible therapeutic option with antibiotics. PATIENTS AND
      METHODS: In our randomized, placebo-controlled double-blind study, 28 patients
      with the confirmed diagnosis of MS [61% relapsing-remitting MS (RR-MS), 32%
      secondary chronic-progressive MS (SP-MS) and 7% primary chronic progressive MS
      (PP-MS)] were treated over a time period of 12 months with three cycles of a 6
      week oral antibiotic therapy with roxithromycin (300 mg per day) or placebo.
      RESULTS: No significant differences were observed in patients with RR-MS
      regarding the expanded disability status scale (EDSS) and the relapse rate when
      comparing treatment with roxithromycin and placebo. CONCLUSION: Our study shows
      that the patients with MS do not profit from a long-term antibiotic treatment
      with roxithromycin compared to placebo treatment. A causative connection between
      bacterial infections with C. pneumonia and MS therefore does seem very unlikely.

PMID- 17180591
TI  - Development of candidemia on caspofungin therapy: a case report.
AB  - Caspofungin, an echinocandin, is approved for use in invasive candidiasis. Few
      cases of break-through candidal infections during caspofungin therapy have been
      reported and none have involved Candida parapsilosis. Here, we report a patient
      who developed multiple post-operative complications after pancreaticoduodenectomy
      for a pancreatic mass, including fungemia due to C. parapsilosis, while on
      caspofungin for treatment of Candida glabrata peritonitis. The fungemia resolved
      after a central venous catheter was removed and therapy was switched from
      caspofungin to amphotericin B lipid complex. Studies of C. parapsilosis
      susceptibility and the pharmacodynamics and drug interactions of caspofungin that
      may contribute to breakthrough fungemia are discussed.

PMID- 17180592
TI  - Myeloradiculitis: a rare event in schistosoma infection.
AB  - Schistosomiasis a parasitic disease caused by trematodes is widely distributed in
      (sub-)tropical countries. Depending on the species the infection manifests
      clinically as gastrointestinal (preferentially Schistosoma mansoni and S.
      japonicum) or urinary (preferentially S. haematobium) disorders. Here we present
      an uncommon case of myeloradiculitis leading to bladder palsy and sensory loss at
      the lower limbs.

PMID- 17180594
TI  - Mycoplasma pneumoniae pericarditis and cardiac tamponade in a 7-year-old girl
      with cystic fibrosis.

PMID- 17180593
TI  - Coexistence of Ramsay Hunt syndrome and varicella-zoster virus encephalitis.
AB  - We describe a patient with Ramsay Hunt syndrome and varicella-zoster virus
      encephalitis. The coexistence of these conditions is rare and to our knowledge
      has not been clearly documented in the English-language literature. We summarize
      the clinical characteristics of our patient and seven similar patients described
      in previous reports, including those published in Japanese. Although concomitant
      diseases such as diabetes and chronic renal failure may lead to an aggressive
      course, all patients described in detail have had good outcomes.

PMID- 17180595
TI  - Evaluation of neuropsychological performance of HIV-infected patients with minor
      motor cognitive dysfunction treated with highly active antiretroviral therapy.

PMID- 17180596
TI  - NKIM-6, a new immortalized human brain capillary endothelial cell line with
      conserved endothelial characteristics.
AB  - Primary human brain capillary endothelial cells (hBCECs) are available only in
      small quantities and have a short life span in vitro; this restricts their use as
      in vitro model for the blood-brain barrier (BBB). To overcome these limitations,
      we have established an immortalized hBCEC line (NKIM-6) by transfection with
      pLXSN16E6E7, which encodes the human papillomavirus type 16 E6 and E7 genes. The
      cell line exhibits an extended life span in vitro and retains its characteristic
      endothelial morphology, endothelial markers, and physiology. Likewise, as
      demonstrated by immunohistochemistry and reverse transcription/polymerase chain
      reaction (RT-PCR), NKIM-6 cells express BBB markers, and the lack of glial,
      neuronal, and epithelial markers confirms their endothelial origin. Moreover,
      with quantitative RT-PCR, we have been able to demonstrate that several ATP
      binding cassette-transporters are expressed in NKIM-6 cells with a conserved
      expression order compared with primary hBCECs. Our results suggest that this cell
      line might be suitable as in vitro model for several aspects of the BBB.

PMID- 17180597
TI  - Expression of retinaldehyde dehydrogenase (RALDH)2 and RALDH3 but not RALDH1 in
      the developing anterior pituitary glands of rats.
AB  - Retinoic acid (RA) plays an important role in cell growth and tissue development
      and is also a regulating factor of pituitary function. However, whether RA is
      generated in the pituitary gland and plays a role as a paracrine and/or autocrine
      hormone is generally unknown. RA is synthesized from retinoids through oxidation
      processes. Dehydrogenases catalyzing the oxidation of retinal to RA are members
      of the retinaldehyde dehydrogenase (RALDH) family. In this study, we examined the
      expression of RALDH1, RALDH2, and RALDH3 mRNA in the rat embryonic pituitary
      gland. By in situ hybridization with digoxigenin-labeled cRNA probes, we detected
      mRNA expression for RALDH2 and RALDH3, but not RALDH1. The expression of RALDH2
      and RALDH3 was located in Rathke's pouch at embryonic day 12.5 (E12.5) and
      subsequently in the developing anterior pituitary gland. We also used
      quantitative real-time polymerase chain reaction to analyze RALDH2 and RALDH3
      mRNA expression levels during the development of the pituitary gland. We found
      that pituitary RALDH2 and RALDH3 mRNA levels were high at E17.5 and decreased
      markedly after birth. Our study is the first to show that RALDH2 and RALDH3, but
      not RALDH1, are expressed in the embryonic anterior pituitary gland of the rat.

PMID- 17180599
TI  - Enameloid/enamel transition through successive tooth replacements in Pleurodeles
      waltl (Lissamphibia, Caudata).
AB  - Study of the evolutionary enameloid/enamel transition suffers from discontinuous
      data in the fossil record, although a developmental enameloid/enamel transition
      exists in living caudates, salamanders and newts. The timing and manner in which
      the enameloid/enamel transition is achieved during caudate ontogeny is of great
      interest, because the caudate situation could reflect events that have occurred
      during evolution. Using light and transmission electron microscopy, we have
      monitored the formation of the upper tooth region in six successive teeth of a
      tooth family (position I) in Pleurodeles waltl from late embryos to young adult.
      Enameloid has only been identified in embryonic tooth I(1) and in larval teeth
      I(2) and I(3). A thin layer of enamel is deposited later by ameloblasts on the
      enameloid surface of these teeth. From post-metamorphic juvenile onwards, teeth
      are covered with enamel only. The collagen-rich enameloid matrix is deposited by
      odontoblasts, which subsequently form dentin. Enameloid, like enamel, mineralizes
      and then matures but ameloblast participation in enameloid matrix deposition has
      not been established. From tooth I(1) to tooth I(3), the enameloid matrix becomes
      ever more dense and increasingly comes to resemble the dentin matrix, although it
      is still subjected to maturation. Our data suggest the absence of an
      enameloid/enamel transition and, instead, the occurrence of an enameloid/dentin
      transition, which seems to result from a progressive slowing down of odontoblast
      activity. As a consequence, the ameloblasts in post-metamorphic teeth appear to
      synthesize the enamel matrix earlier than in larval teeth.

PMID- 17180598
TI  - Gene expression during chemically induced liver fibrosis: effect of halofuginone
      on TGF-beta signaling.
AB  - Hepatic fibrosis is associated with the activation of stellate cells (HSCs), the
      major source of extracellular matrix (ECM) proteins. Transforming growth factor
      beta (TGF-beta), signaling via Smad3, is the most profibrogenic cytokine and the
      major promoter of ECM synthesis. Halofuginone, an inhibitor of liver fibrosis,
      inhibits TGF-beta-dependent Smad3 phosphorylation in human HSCs in culture. We
      have used transcriptional profiling to evaluate the effect of halofuginone on
      gene expression during the progression of thioacetamide (TAA)-induced liver
      fibrosis in the rat and have focused on genes that are associated with TGF-beta.
      TAA treatment causes alterations in the expression of 7% of liver genes.
      Halofuginone treatment prevents the changes in the expression of 41% of these
      genes and results in the inhibition of HSC activation and collagen synthesis.
      During the early stages of the disease, halofuginone affects genes involved in
      alcohol, lipid, protein, and phosphate metabolism and cell adhesion and, at later
      stages, in the cell cycle (cell development, differentiation, cell proliferation,
      and apoptosis). The activation of TGF-beta-dependent genes, such as tartrate
      resistant acid phosphatase, its putative substrate osteopontin, stellate cell
      activation-association protein, and fibrillin-1, during chemically induced
      fibrosis is prevented by halofuginone. This study thus highlights the role of TGF
      beta signaling in liver fibrosis and especially its potential for pharmacological
      intervention. Halofuginone, which has demonstrated efficacy and tolerance in
      animals and humans, could become an effective and novel therapy for liver
      fibrosis.

PMID- 17180602
TI  - Comment on Varpula et al.: Mixed venous oxygen saturation cannot be estimated by
      central venous oxygen saturation in septic shock.

PMID- 17180600
TI  - In vivo assessment of [11C]MRB as a prospective PET ligand for imaging the
      norepinephrine transporter.
AB  - PURPOSE: Antagonism of norepinephrine reuptake is now an important
      pharmacological strategy in the treatment of anxiety and depressive disorders,
      and many antidepressants have substantial potential occupancy of the
      norepinephrine transporter (NET) at recommended dosages. Despite the importance
      of understanding this transporter's role in psychiatric disease and treatment, a
      suitable radioligand for studying NET has been slow to emerge. (S,S)
      Methylreboxetine (MRB) is among the more promising ligands recently adapted for
      positron emission tomography (PET), and the present study aimed to evaluate its
      potential for use in higher primates. METHODS: Affinities for various brain
      targets were determined in vitro. PET studies were conducted in baboon under both
      test-retest and blocking conditions using 1 mg/kg nisoxetine. RESULTS: MRB has
      sixfold higher affinity for NET than the serotonin transporter, and negligible
      affinity for other sites. PET studies in baboons showed little regional
      heterogeneity in binding and were minimally affected by pretreatment with the NET
      antagonist nisoxetine. CONCLUSION: Despite improvement over previous ligands for
      imaging NET in vivo, the low signal to noise ratio indicates [(11)C]MRB lacks
      sensitivity and reliability as a PET radiotracer in humans.

PMID- 17180603
TI  - [Expert opinion aspects of thrombosis prophylaxis].
AB  - The boom in medical liability shows no sign of easing even for thrombosis
      prophylaxis, so that it is becoming increasingly more common that experts must
      decide whether this has been correctly carried out. From this point of view they
      are legally only "assistants" to the judge, but practically they make the
      decision in liability disputes. It is therefore of great importance that the
      experts fulfil their key role in an unbiased and professionally competent manner
      and limit their opinions to their own field of expertise. They must also be fully
      aware of the different prerequisites for liability in both civil and criminal
      proceedings and the legal definitions of, for example the terms "standard medical
      professional practice", "grossly" negligent treatment, "a probability bordering
      on certainty", "obligation to the evidential value" and be familiar with the
      facts in question. Without this necessary knowledge in the legal field,
      regrettable judicial errors will always reoccur.

PMID- 17180604
TI  - [Pulmonary embolism and deep vein thrombosis in the inferior vena cava affected
      by a rare anomaly].
AB  - Persistent left-sided inferior vena cava (VCI) is a rare venous anomaly, its
      prevalence being estimated at 0.2-0.5%. Thrombotic occlusion of a VCI has been
      reported in only a few of these cases. We report the case of a 24-year old woman
      who suffered an acute thrombosis in a left-sided VCI and recurrent pulmonary
      embolism. After thrombectomy the course was uneventful. The diagnostic approach
      and the treatment strategy are discussed with reference to the literature.

PMID- 17180605
TI  - [Motor vehicle accidents with entrapment. A medical and technical investigation
      of crash mechanism, injury pattern and severity of entrapment of motor vehicle
      occupants between 1983 and 2003].
AB  - AIM: Crash mechanisms, injury patterns, and severity of injury of entrapped motor
      vehicle occupants were analysed by the Accident Research Unit's scientific teams
      between 1983 and 2003. RESULTS: Of the 1281 vehicle passenger entrapments in our
      study, 18.3% happened on highways, 25.6% on federal roads, 35.9% on country
      roads, and 18.3% on city roads. Of those involved, 69.9% were drivers, 19.4% were
      front passengers, and 8.5% were rear passengers. Coinvolved objects in car
      collisions were: other cars 30.9%, trucks 50.2%, objects 18.6%, and motorbikes
      0.3%. Coinvolved objects in truck collisions were: other trucks 61.8% and objects
      38.2%. The mean Delta-V was 42 km/h (cars 46.2, trucks 32.2). Maximum AIS levels
      were 31% I, 25.2% II, 19.4% III, 7.8% IV, 7.8% V, and 8.6% VI. Of injuries, 68.7%
      were to the head, 23.5% to the neck, 50.8% to the chest, 43.6% to upper
      extremities, 15.4% to the abdomen, 16.4% to the pelvis, and 52.9% to lower
      extremities. The incidence of multiple injuries (ISS>16) was 23.7%, and mortality
      was 15.9%. CONCLUSION: Car drivers are more at risk of accidents with entrapment
      on rural streets, and truck drivers are more at risk on highways. In most cases
      car occupants crash with trucks or other cars, and truck drivers collide more
      frequently with other trucks or objects. Besides a high degree of severe single
      injuries, there is also a high incidence of multiple injury victims and high
      mortality. Of the fatalities, 74.5% occur during the preclinical course and 24.5%
      during the clinical course.

PMID- 17180606
TI  - [A sizeable chance--surgical management of profound obesity concurrent with post
      traumatic osteoarthrosis].
AB  - In times of plentiful nutrition an environmental advantage turns into a problem -
      obesity. Apart from an increase in morbidity and overall mortality the
      development of osteoarthrosis is well documented. Pre-arthrotic conditions may
      arise from trauma and can lead, depending on the pattern of injury, to full-blown
      arthrosis. The presence of obesity can play the role of a relevant progressive
      factor in this setting. Here we report about the case of an obese man (BMI 53.5
      kg/m(2)), who suffered a fracture of the femoral head with acetabular
      participation (Pipkin IV) as well as a fracture of the tibial plateau. Operative
      management and rehabilitation were followed by gastric bypass surgery for weight
      reduction. The case is discussed with regard to the present literature.

PMID- 17180607
TI  - [Photodynamic therapy of AMD for the first (better sight) and the second (worse
      sight) eyes].
AB  - BACKGROUND: Photodynamic therapy (PDT) is the standard treatment procedure for
      many forms of exudative and/or neovascular AMD. Despite therapy, visual acuity
      often drops to low vision levels. The cost efficiency of treating the eye in
      which vision is worse is therefore the subject of some controversy. PATIENTS AND
      METHODS: A retrospective case-control study was conducted in all patients who
      were treated with PDT at the Universitatsspital Zurich between September 1999 and
      November 2004. Each patient's first (with worse vision) and second (with better
      vision) eyes were compared for situation on presentation and course during
      treatment. RESULTS: In 117/228 cases (51.3%) visual acuity of the treated eye was
      better than (or identical to) that of the fellow eye at presentation. Visual
      acuity before therapy was an average of 0.58+/-0.27 logMAR [Snellen: 0.26 (0.14
      0.49)] in the eyes with better visual acuity and 0.69+/-0.4 logMAR [Snellen 0.20
      (0.08-0.51)] in the fellow eyes (p=0.015). After therapy there was no significant
      difference between the patient groups in visual acuity or in the magnitude of any
      change in visual acuity, or in lesion size or change in lesion size. CONCLUSION:
      The outcome of PDT of a second eye (with better visual acuity) is not
      significantly better than the result obtained in the first eye (the one with
      worse visual acuity initially).

PMID- 17180608
TI  - Spread of a single multiresistant methicillin-resistant Staphylococcus aureus
      clone carrying a variant of staphylococcal cassette chromosome mec type III
      isolated in a university hospital.
AB  - The purpose of the study was the molecular characterization of methicillin
      resistant Staphylococcus aureus (MRSA) isolates cultured from patients treated in
      seven wards of a university hospital in Lublin, Poland, over a 14-month period.
      Eleven nosocomial MRSA isolates were analyzed. Phenotypic identification of the
      isolates as MRSA was confirmed by the detection of the nuc and mecA genes using a
      multiplex PCR assay. The MRSA isolates were further characterized by pulsed-field
      gel electrophoresis, 16S-23S rRNA spacer length polymorphism analysis, and the
      simplex and multiplex SCCmec PCR assays. The MRSA isolates were found to be
      multiresistant: in addition to resistance to beta-lactam agents, they
      demonstrated resistance to ciprofloxacin, tetracycline, erythromycin, and
      gentamicin. The MRSA isolates were genetically identical and shared common pulsed
      field gel electrophoresis profiles and 16S-23S rRNA spacer length polymorphism
      profiles. The PCR-based method revealed that the profile of the Lublin clone was
      identical to that of the Brazilian pandemic MRSA isolates. By SCCmec typing, all
      MRSA isolates harbored the C variant of the SCCmec type III that differed from
      the typical SCCmec type III pattern by the lack of locus F (414 bp). The results
      of this study indicate the spread of a single, multiresistant, MRSA clone in
      various wards of a university hospital over a 14-month period. The SCCmec
      structure harbored by the Lublin clone has previously been identified among
      Polish MRSA isolates representing the HoMRSA-Pol1 clone. The data from this study
      indicate that the Lublin MRSA clone is most probably genetically related to the
      HoMRSA-Pol1 clone. Moreover, this latter clone belongs to ST239, the same
      sequence type as the Hungarian and Brazilian pandemic MRSA isolates.

PMID- 17180609
TI  - Retrospective analysis of 49 cases of brain abscess and review of the literature.
AB  - The case records of 49 patients discharged from St George's Hospital, London,
      between December 2000 and March 2004 with the diagnosis of brain abscess were
      reviewed in order to document the epidemiology, causes, treatment, and prognostic
      factors associated with brain abscess. Brain abscess occurred at all ages, more
      frequently in men than in women. Headache and altered mental status were common
      presenting symptoms. The frontal lobe was the most common site. Streptococcal
      infection was seen most commonly, but staphylococcal infection predominated in
      cases following neurosurgery. Computed tomography provided sufficient diagnostic
      information in most cases. All but five patients had early surgical drainage.
      Cefotaxime and metronidazole were used most often for empirical therapy. Thirty
      nine patients recovered fully or had minimal incapacity. Five patients died.
      Patients with underlying cranial neoplasms or medical conditions had a worse
      outcome than those with a contiguous focus of infection or post-traumatic
      abscess. Changes in disease pattern were determined by comparison to a literature
      review. A PubMed search of the literature using the keywords "brain abscess" was
      undertaken, and identified papers and relevant citations were reviewed. Compared
      to earlier series, there was a marked decrease in the number of cases of brain
      abscess secondary to otitis media and congenital heart disease. There was an
      increase in the number of cases of brain abscess secondary to neurosurgery and
      trauma. Changes in the epidemiology of predisposing conditions for brain abscess
      are associated with changes in the patient population and causative organisms.
      Though still a potentially fatal infection, there have been recent improvements
      in diagnosis, treatment, and outcome.

PMID- 17180610
TI  - Magnetic resonance imaging of iron-oxide labeled SK-Mel 28 human melanoma cells
      in the chick embryo using a clinical whole body MRI scanner.
AB  - PURPOSE: To evaluate advantages and limitations of magnetic resonance imaging
      (MRI) to monitor the migration of superparamagnetic iron oxide (SPIO) labeled
      cells in the chick embryo. MATERIALS AND METHODS: Labeled human SK-Mel 28
      melanoma cells were injected into the E2 chick embryo neural tube. Embryos were
      examined with a clinical 3 T MRI whole body system using 3D T*(2)-weighted
      sequences with isotropic spatial resolutions of 0.3-1.0 mm. MR-measurements of
      embryos were performed 2 - 16 days after cell injection. MRI findings were
      verified by dissection and histology. RESULTS: After injection, melanoma cells
      formed aggregations that were detectable in the neural tube as signal voids in MR
      images from day 2 after injection. Emigrating cells later left MRI detectable
      tracks. Aggregates that remained in the neural tube left label that was absorbed
      by glia cells. In E18 chick embryos, signals of haematopoiesis interfered with
      signals from cell labeling. CONCLUSION: It was shown that SK-Mel 28 cells will
      resume the neural crest pathways after injection into the embryonic micro
      environment. SPIO cell labeling allows monitoring of transplanted melanoma cells
      during embryonic development. MRI using the standard clinical equipment promises
      to be valuable for high-sensitive monitoring of ex-vivo labeled cells in the
      chick embryo.

PMID- 17180612
TI  - Electroretinographic findings in the Standard Wire Haired Dachshund with
      inherited early onset cone-rod dystrophy.
AB  - PURPOSE: To describe electroretinographic (ERG) findings in a strain of Standard
      Wire Haired Dachshund (SWHD)-derived dogs at the ages of approximately 5, 8 and
      52 weeks selected for inherited early onset cone-rod dystrophy. METHODS: Nineteen
      affected and 13 age-matched control SWHDs were included in the study. All dogs
      were subjected to standardized bilateral Ganzfeld ERGs and ophthalmoscopic
      examinations at regular intervals. RESULTS: Photopic cone-derived ERG amplitudes
      were significantly lower and never reached similar levels as those recorded in
      control dogs. In affected dogs there was no increase with age in amplitudes
      recorded using 30.1 and 50.1 Hz flicker stimuli. In contrast, in the control
      groups the photopic b-wave amplitude recorded at 50.1 Hz increased significantly
      from age 5 to 8 and from 5 to 52 weeks. In affected animals, scotopic rod-derived
      amplitudes were significantly lower for most recordings compared to those of
      control dogs, although they increased significantly from age 5 to 8 weeks in both
      affected and controls. Both a- and b-wave implicit times were significantly
      longer in the youngest affected group when compared to the age-matched control
      group at 0.6 log cd s/m(2) and 5.1 Hz single flash light stimuli. In the control
      dogs, however, there was a significant shortening in a-wave implicit times from
      age 5 to 8 weeks, and in a- and b-wave implicit times recorded at 5.1 Hz single
      flash stimuli from age 5 to 52 weeks. CONCLUSIONS: The described retinal
      degeneration in the SWHD is an early onset cone-rod dystrophy, initially
      affecting the cone system most severely. Early functional changes are seen in the
      rod system as well. Inner retina also appears affected already at a young age
      with findings indicating postsynaptic functional changes already at the earliest
      time point studied, at age 5 weeks. The present study further indicates that the
      canine retina reaches maturity later than previously reported, or that there
      exist major breed differences.

PMID- 17180611
TI  - 31P MR spectroscopy and in vitro markers of oxidative capacity in type 2 diabetes
      patients.
AB  - BACKGROUND: Skeletal muscle mitochondrial function in type 2 diabetes (T2D) is
      currently being studied intensively. In vivo (31)P magnetic resonance
      spectroscopy ((31)P MRS) is a noninvasive tool used to measure mitochondrial
      respiratory function (MIFU) in skeletal muscle tissue. However, microvascular co
      morbidity in long-standing T2D can interfere with the (31)P MRS methodology. AIM:
      To compare (31)P MRS-derived parameters describing in vivo MIFU with an in vitro
      assessment of muscle respiratory capacity and muscle fiber-type composition in
      T2D patients. METHODS: (31)P MRS was applied in long-standing, insulin-treated
      T2D patients. (31)P MRS markers of MIFU were measured in the M. vastus lateralis.
      Muscle biopsy samples were collected from the same muscle and analyzed for
      succinate dehydrogenase activity (SDH) and fiber-type distribution. RESULTS:
      Several (31)P MRS parameters of MIFU showed moderate to good correlations with
      the percentage of type I fibers and type I fiber-specific SDH activity (Pearson's
      R between 0.70 and 0.75). In vivo and in vitro parameters of local mitochondrial
      respiration also correlated well with whole-body fitness levels (VO (2peak)) in
      these patients (Pearson's R between 0.62 and 0.90). CONCLUSION: Good correlations
      exist between in vivo and in vitro measurements of MIFU in long-standing insulin
      treated T2D subjects, which are qualitatively and quantitatively consistent with
      previous results measured in healthy subjects. This justifies the use of (31)P
      MRS to measure MIFU in relation to T2D.

PMID- 17180613
TI  - Multifocal ERG findings in carriers of X-linked retinoschisis.
AB  - PURPOSE: To determine whether retinal dysfunction in obligate carriers of X
      linked retinoschisis (XLRS) could be observed in local electroretinographic
      responses obtained with the multifocal electroretinogram (mfERG). METHODS: Nine
      obligate carriers of XLRS (mean age, 46.2 years) were examined for the study.
      Examination of each carrier included an ocular examination and mfERG testing. For
      the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal
      area of approximately 40 degrees in diameter. The amplitudes and implicit times
      in each location for the mfERG were compared with the corresponding values
      determined for a group of 34 normally-sighted, age-similar control subjects.
      RESULTS: Mapping of 103 local electroretinographic response amplitudes and
      implicit times within a central 40 degrees area with the mfERG showed regions of
      reduced mfERG amplitudes and delayed implicit times in two of nine carriers.
      CONCLUSIONS: The mfERG demonstrated areas of retinal dysfunction in two carriers
      of XLRS. When present, retinal dysfunction was evident in the presence of a
      normal-appearing fundus. Multifocal ERG testing can be useful for identifying
      some carriers of XLRS.

PMID- 17180614
TI  - Last Glacial mammals in South America: a new scenario from the Tarija Basin
      (Bolivia).
AB  - The chronology, sedimentary history, and paleoecology of the Tarija Basin
      (Bolivia), one of the richest Pleistocene mammalian sites in South America, are
      revised here based on a multidisciplinary study, including stratigraphy,
      sedimentology, geomorphology, paleontology, isotope geochemistry, and (14)C
      geochronology. Previous studies have indicated a Middle Pleistocene age for this
      classic locality. We have been able to obtain a series of (14)C dates
      encompassing all the fossil-bearing sequences previously studied in the Tarija
      Basin. The dated layers range in age from about 44,000 to 21,000 radiocarbon
      years before present (BP), indicating that the Tarija fauna is much younger than
      previously thought. Glacial advances correlated to marine isotopic stages (MIS) 4
      and 2 (ca. 62 and 20 ka BP, respectively) are also documented at the base and at
      the very top of the Tarija-Padcaya succession, respectively, indicating that the
      Bolivian Altiplano was not dry but sustained an ice cap during the Last Glacial
      Maximum. The results of this multidisciplinary study enable us to redefine the
      chronological limits of the Tarija sequence and of its faunal assemblage and to
      shift this paleontological, paleoclimatological, and paleoecological framework to
      the time interval from MIS 4 to MIS 2.

PMID- 17180615
TI  - Slanted joint axes of the stick insect antenna: an adaptation to tactile acuity.
AB  - Like many flightless, obligatory walking insects, the stick insect Carausius
      morosus makes intensive use of active antennal movements for tactile near range
      exploration and orientation. The antennal joints of C. morosus have a peculiar
      oblique and non-orthogonal joint axis arrangement. Moreover, this arrangement is
      known to differ from that in crickets (Ensifera), locusts (Caelifera) and
      cockroaches (Blattodea), all of which have an orthogonal joint axis arrangement.
      Our hypothesis was that the situation found in C. morosus represents an important
      evolutionary trait of the order of stick and leaf insects (Phasmatodea). If this
      was true, it should be common to other species of the Phasmatodea. The objective
      of this comparative study was to resolve this question. We have measured the
      joint axis orientation of the head-scape and scape-pedicel joints along with
      other parameters that affect the tactile efficiency of the antenna. The obtained
      result was a complete kinematic description of the antenna. This was used to
      determine the size and location of kinematic out-of-reach zones, which are
      indicators of tactile acuity. We show that the oblique and non-orthogonal
      arrangement is common to eight species from six sub-families indicating that it
      is a synapomorphic character of the Euphasmatodea. This character can improve
      tactile acuity compared to the situation in crickets, locusts and cockroaches.
      Finally, because molecular data of a recent study indicate that the Phasmatodea
      may have evolved as flightless, obligatory walkers, we argue that the antennal
      joint axis arrangement of the Euphasmatodea reflects an evolutionary adaptation
      to tactile near range exploration during terrestrial locomotion.

PMID- 17180616
TI  - Inhibition of eryptosis and intraerythrocytic growth of Plasmodium falciparum by
      flufenamic acid.
AB  - Non-selective (NSC) cation channels participate in the Ca(2+) leak of human
      erythrocytes. Sustained activity of these channels triggers suicidal erythrocyte
      death (eryptosis), which is characterized by Ca(2+)-stimulated cell shrinkage and
      phosphatidylserine (PS) exposure. PS-exposing erythrocytes are rapidly cleared
      from circulating blood. PGE(2) activates the NSC channels, and erythrocyte PGE(2)
      formation is stimulated by a decrease in intra- or extracellular Cl(-)
      concentration. In addition, the intraerythrocytic malaria parasite Plasmodium
      falciparum activates the NSC channels, most probably to accomplish Na(+) and
      Ca(2+) entry into the erythrocyte cytosol required for parasite development. By
      Ca(2+) uptake the parasite maintains a low Ca(2+) concentration in the
      erythrocyte cytosol and thus delays the suicidal death of the host erythrocyte.
      Flufenamic acid has previously been shown to inhibit NSC channels. The present
      study thus explored the effect of flufenamic acid on erythrocyte Ca(2+) entry, on
      suicidal erythrocyte death and on intraerythrocytic growth of P. falciparum.
      Within 48 h, replacement of extracellular Cl(-) with gluconate or application of
      PGE(2) (50 microM) increased Fluo3 fluorescence reflecting cytosolic Ca(2+)
      activity, decreased forward scatter reflecting cell volume and increased annexin
      V binding reflecting PS exposure in FACS analysis. All those effects were
      significantly blunted in the presence of flufenamic acid (10 microM). Flufenamic
      acid (25 microM) further significantly delayed the intraerythrocytic growth of P.
      falciparum and the PS exposure of the infected erythrocytes. The present
      observations disclose a novel effect of flufenamic acid, which may allow the
      pharmacological manipulation of erythrocyte survival and the course of malaria.

PMID- 17180617
TI  - Disruption of the US pre-exposure effect and latent inhibition in two-way active
      avoidance by systemic amphetamine in C57BL/6 mice.
AB  - RATIONALE: Pre-exposure to either one of the two to-be-associated stimuli alone
      is known to reduce the efficiency of the learning of their association when they
      are subsequently paired explicitly. In classical conditioning, pre-exposure to
      the conditioned stimulus (CS) gives rise to latent inhibition (LI); and pre
      exposure to the unconditioned stimulus (US) results in the US pre-exposure effect
      (USPEE). Considerable evidence supports an important role of central dopamine in
      the regulation and modulation of LI; it has been suggested that the USPEE may be
      similarly controlled by dopamine, but this parallelism has only been directly
      demonstrated in the conditioned taste aversion paradigm. OBJECTIVE: The present
      study tested this hypothesis by comparing the efficacy of systemic amphetamine
      treatment to affect the expression of LI and the USPEE in a two-way active
      avoidance paradigm. METHODS: C57BL/6 male mice were tested in active avoidance
      using a tone CS and a foot-shock US. Twenty-four hours before, they were pre
      exposed to 100 presentations of the CS or the US, or to the test apparatus only.
      Amphetamine (2.5 mg/kg) or saline was administered before stimulus pre-exposure
      and conditioned avoidance test, in which the mice learned to avoid the shock by
      shuttling in response to the tone. RESULTS: Amphetamine disrupted both stimulus
      pre-exposure effects, thus, lending further support to the hypothesis that the
      USPEE is similar to LI in its sensitivity to dopamine receptor agonist. Hence,
      the USPEE paradigm may represent a valuable addition to the study of dopamine
      sensitive processes of selective learning currently implicated in LI and Kamin
      blocking.

PMID- 17180618
TI  - Risk of adverse behavioral effects with pediatric use of antidepressants.
AB  - OBJECTIVES: This article reviews evidence that led the Food and Drug
      Administration to issue a "black box" warning about the risk of "suicidality"
      (suicidal thoughts and behavior) in children and adolescents during treatment
      with antidepressants. RESULTS: Re-analysis of data from randomized clinical
      trials of antidepressants in the pediatric population revealed a significantly
      greater overall (all drugs across all indications) risk ratio for drug 1.95 (95%
      Cl, 1.28-2.98) compared to placebo in this sample of approximately 4,000
      subjects. DISCUSSION: The essential message of the "black box" is to remind
      prescribers and consumers about the importance of monitoring closely for adverse
      behavioral changes during the initiation of (or changes in) antidepressant
      therapy. Possible mechanisms that might account for this phenomenon, particularly
      the so-called activation syndrome, are discussed. CONCLUSION: Empirical studies
      are needed to identify the precursors of suicidality and to predict which
      individuals are most susceptible to adverse behavioral side effects of
      antidepressants.

PMID- 17180620
TI  - Simultaneous determination of beta-lactamic antibiotics by a new high-performance
      low-pressure chromatographic system using a multisyringe burette coupled to a
      monolithic column (MSC).
AB  - A technique based on multisyringe chromatography (MSC) was developed to determine
      three beta-lactamic antibiotics. Amoxicillin (AMOXI), ampicillin (AMPI) and
      cephalexin (CEPHA) were analyzed using a system with a very simple design and
      very low-cost equipment consisting of a multisyringe module, three low-pressure
      solenoid valves, a monolithic Chromolith Flash RP-18e column and a diode array
      spectrophotometric detector monitoring at 250 nm. Mobile phases containing
      methanol:acetic acid (0.1 M)-sodium acetate (0.1 M), pH 6.2, were tested for
      various ratios of methanol:acetic acid-sodium acetate, but a ratio of 10:90 gave
      optimum results with a flow rate of 2 ml min(-1). Validation parameters were
      evaluated for amoxicillin. The response to amoxicillin was linear over the range
      0.04-0.4 mg/mL, with a correlation coefficient of 0.9996; precisions, evaluated
      as the repeatability for 0.04, 0.16 and 0.4 mg/mL amoxicillin, were 0.6%, 0.1%
      and 0.6%, respectively. Recovery from a generic formulation of amoxicillin was
      evaluated. The method showed selectivity in the presence of excipients commonly
      used in capsules, and satisfactory specificity was observed for amoxicillin and
      hydrolytic degradation products. The linearity was also evaluated for cephalexin
      and ampicillin. The conditions selected for MSC separation were compared with
      those for a HPLC system, and similar results were obtained in terms of
      chromatographic parameters but a difference in retention times was observed.

PMID- 17180619
TI  - Effects of elevated plasma tryptophan on brain activation associated with the
      Stroop task.
AB  - RATIONALE: Central fatigue, such as that found in chronic fatigue syndrome, is a
      state in which cognition and action require increasing effort and performance is
      impaired without evidence for reduced peripheral motor responsiveness. Previous
      studies identified functional changes in subcortical regions in patients who
      experience central fatigue but did not address neural correlates of the
      subjective experience of fatigue. OBJECTIVES: This study investigated responses
      to acute tryptophan feeding (after administration of 30 mg/kg body mass) using
      functional magnetic resonance imaging to investigate neural correlates of central
      fatigue during a cognitively demanding exercise, the counting Stroop task.
      MATERIALS AND METHODS: In a double-blind, cross-over study, eight subjects
      ingested L: -tryptophan (Trp) or placebo (Plac) on two separate test days.
      Neutral (N) and interference (I) Stroop tasks were carried out. RESULTS: Plasma
      free tryptophan (p[FT]) increased tenfold after L: -Trp administration (P <
      0.01). Although reaction times were longer after Trp (mean+/-SD, Plac-Neut 669 +/
      163 ms, I 715 +/- 174 ms, P < 0.01; Trp-Neut 712 +/- 193 ms, I 761 +/- 198 ms, P
      < 0.05), the Stroop effect was not significantly different between Plac and Trp.
      L: -Trp administration was associated with relatively decreased activation in
      regions, including the left postcentral, angular, inferior frontal, and the
      lateral orbital gyri and the inferior frontal sulcus relative to Plac. Relatively
      increased activation was found after Trp in the left precuneus and in the
      posterior cingulate gyrus. CONCLUSIONS: Thus, Trp administration before the
      Stroop task caused distributed functional changes in primary sensory and in
      multimodal neocortex, including changes in a brain region, the activity of which
      has been shown previously to vary with conscious awareness (precuneus). Previous
      reports suggest that primary mechanisms of central fatigue may be predominantly
      subcortical. The present results demonstrate that neocortical activity changes
      are also found. Whether this activity contributes to the primary mechanisms
      underlying central fatigue or not, the neocortical activity changes may provide
      an index of the conscious experience.

PMID- 17180621
TI  - Plasma protein distribution and its impact on pharmacokinetics of liposomal
      amphotericin B in paediatric patients with malignant diseases.
AB  - OBJECTIVE: This study investigates the association of liposomal amphotericin B (L
      AmB) with plasma proteins and its impact on the pharmacokinetics of L-AmB in
      paediatric patients with malignant diseases. METHODS: Paediatric oncology
      patients (n = 39) who received multiple-doses of L-AmB were recruited into this
      study. The association of the drug with plasma lipoprotein was investigated using
      single vertical spin density gradient ultracentrifugation and quantitated with a
      validated HPLC assay. The unbound amphotericin B (AmB) in the plasma was
      separated by ultrafiltration and determined with a validated LC/MS/MS assay.
      RESULTS: The ex vivo lipoprotein distribution of L-AmB found that 68.3 +/- 11.8%
      of the drug was associated with the high density lipoprotein (HDL) fraction,
      which demonstrated a significant inverse correlation with posterior Bayesian
      estimates of L-AmB clearance (r = -0.690, p < 0.01). The average of unbound
      fraction of AmB in plasma of patients administered with L-AmB was 0.005, but its
      relationship with L-AmB clearance did not reach a statistical significance.
      CONCLUSION: L-AmB displays different lipoprotein distribution profile from that
      of the conventional AmB formulation, with L-AmB preferentially associated with
      HDL in plasma. The inverse correlation of L-AmB clearance to its HDL distribution
      contributes to the difference in the pharmacokinetic profile of L-AmB.

PMID- 17180623
TI  - High rate of mutation reporter gene inactivation during human T cell
      proliferation.
AB  - Caspase activation and degradation of deoxyribonucleic acid (DNA) damage response
      factors occur during in vitro T-cell proliferation, and an increased frequency of
      hypoxanthine-guanine phosphoribosyltransferase (HPRT)-negative variants have been
      reported in conditions associated with in vivo T-cell proliferation. We have
      applied two human somatic cell mutation reporter assays, for the HPRT and
      phosphatidylinositol glycan class A (PIG-A) genes, to human T cells activated in
      vitro with anti-CD3 and anti-CD28. We demonstrate proliferation throughout 6
      weeks of cultivation, and find that the frequency of variant cells phenotypically
      negative for HPRT and PIG-A, respectively, increases from 10(-5) up to 10(-3) 
      10(-2). We also report preliminary evidence for low-density CpG methylation in
      the HPRT promoter suggesting that epigenetic modification may contribute to this
      markedly heightened rate of gene inactivation.

PMID- 17180622
TI  - Structure, dynamics and topology of membrane polypeptides by oriented 2H solid
      state NMR spectroscopy.
AB  - Knowledge of the structure, dynamics and interactions of polypeptides when
      associated with phospholipid bilayers is key to understanding the functional
      mechanisms of channels, antibiotics, signal- or translocation peptides. Solid
      state NMR spectroscopy on samples uniaxially aligned relative to the magnetic
      field direction offers means to determine the alignment of polypeptide bonds and
      domains relative to the bilayer normal. Using this approach the (15)N chemical
      shift of amide bonds provides a direct indicator of the approximate helical tilt,
      whereas the (2)H solid-state NMR spectra acquired from peptides labelled with
      3,3,3-(2)H(3)-alanines contain valuable complimentary information for a more
      accurate analysis of tilt and rotation pitch angles. The deuterium NMR line
      shapes are highly sensitive to small variations in the alignment of the C(alpha)
      C(beta) bond relative to the magnetic field direction and, therefore, also the
      orientational distribution of helices relative to the membrane normal. When the
      oriented membrane samples are investigated with their normal perpendicular to the
      magnetic field direction, the rate of rotational diffusion can be determined in a
      semi-quantitative manner and thereby the aggregation state of the peptides can be
      analysed. Here the deuterium NMR approach is first introduced showing results
      from model amphipathic helices. Thereafter investigations of the viral channel
      peptides Vpu(1-27) and Influenza A M2(22-46) are shown. Whereas the (15)N
      chemical shift data confirm the transmembrane helix alignments of these
      hydrophobic sequences, the deuterium spectra indicate considerable mosaic spread
      in the helix orientations. At least two peptide populations with differing
      rotational correlation times are apparent in the deuterium spectra of the viral
      channels suggesting an equilibrium between monomeric peptides and oligomeric
      channel configurations under conditions where solid-state NMR structural studies
      of these peptides have previously been performed.

PMID- 17180624
TI  - Is non-operative intussusception reduction effective in older children? Ten-year
      experience in a university affiliated medical center.
AB  - Ileo-colic intussusception in older children is frequently caused by a
      pathological lead point. Therefore, in many cases, no attempts at hydrostatic or
      air reduction are performed in non-pediatric hospitals. This study summarizes our
      experience in management of intussusception in children aged 3 years or older, in
      order to determine its efficacy and safety in this age group. We retrospectively
      reviewed medical records and radiological images of 26 cases of intussusception
      in 24 children older than 3 years admitted to our hospital over a 10-year period.
      In one child no attempt of reduction was made. Three children underwent
      unsuccessful imaging-guided reduction and an underlying tumor was identified at
      surgery and resected. In 18 cases air reduction was successful and no
      pathological lead point was discovered. In four children hydrostatic or air
      reductions failed. Manual reduction was performed, with no predisposing cause
      found. No complications were observed in any of our patients. Older age is not a
      contraindication for imaging-guided intussusception reduction attempt. Most of
      these patients can benefit from such an attempt, thereby avoiding surgery.

PMID- 17180625
TI  - Complete genome sequence of an isolate of Papaya ringspot virus from India.

PMID- 17180626
TI  - Enteric caliciviruses in domestic pigs in Hungary.
AB  - Caliciviruses closely related to human norovirus and sapovirus were recently
      detected in domestic pigs, causing discussions about the animal reservoir and the
      potential for zoonotic transmission to humans. To detect porcine caliciviruses,
      17 fecal samples collected on two swine farms in southwestern Hungary were tested
      by reverse transcription-polymerase chain reaction. Three (17.6%) samples were
      positive for caliciviruses. This study confirms the presence of caliciviruses,
      both porcine sapovirus (genus Sapovirus) and porcine norovirus (genus Norovirus),
      in domestic pigs in Hungary and provides additional information on the viral
      genetic diversity and relationship to viruses referred to as human caliciviruses.

PMID- 17180629
TI  - Diagnostic sensitivity of contrast swallow for leakage after gastric resection.
AB  - INTRODUCTION: We examined the clinical manifestations and computed tomography
      findings of patients with leakage after gastrectomy for cancer and determined the
      sensitivity of the contrast swallow for the leakage diagnosis. METHODS: The
      medical records of 331 consecutive patients undergoing gastrectomy between
      January 1992 and December 2003 were reviewed. Routine contrast swallow was
      performed in all patients before oral intake. Once leakage was suspected, an
      emergency contrast swallow was performed and its diagnostic sensitivity
      determined. RESULTS: In total, leakage was diagnosed 9 of 17 times by the
      contrast swallow, for a diagnostic sensitivity of 53%. The clinical signs or
      another imaging modality often corrected the misdiagnosis. CONCLUSIONS: The
      diagnostic sensitivity of contrast swallow for leakage after gastrectomy was low.
      Therefore, if we employ the contrast swallow technique, we should keep in mind
      its low sensitivity.

PMID- 17180630
TI  - Parathyroid cyst: often mistaken for a thyroid cyst.
AB  - INTRODUCTION: Parathyroid cysts are rare but clinically significant lesions. They
      can be functional, mistaken for a thyroid cyst, and/or managed nonoperatively on
      occasion. METHODS: We identified seven patients (1 male, 6 females) with the
      diagnosis of parathyroid cyst from 1998 to 2003. RESULTS: Altogether, 33% of the
      patients had functional cysts. Sestamibi scans were performed in three of the
      seven patients, including two with functional cysts; none showed focal uptake. In
      toto, six of the seven cysts (86%) were found in an inferior parathyroid gland.
      All of the cysts had crystal-clear aspirate. C-terminal parathormone (PTH) levels
      were obtained from the aspirate from five of the seven (71%) patients. The mean
      level was 269,736 pg/ml (1970-1,268,074 pg/ml). Surgery was performed in three of
      the seven (43%) patients. All patients who underwent surgery improved
      postoperatively based on symptoms and serum levels of calcium and PTH. The four
      patients (57%) who were treated nonoperatively were subjected to aspiration
      alone; three (75%) of those patients required multiple aspirations. CONCLUSIONS:
      Most parathyroid cysts are nonfunctional and are rarely symptomatic. They are
      usually located in an inferior gland. If aspirated, most of the cysts
      reaccumulate fluid. Operative management is usually straightforward and
      alleviates symptoms and any biochemical abnormalities caused by the cyst.

PMID- 17180631
TI  - General health mediates the relationship between loneliness, life satisfaction
      and depression. A study with Malaysian medical students.
AB  - OBJECTIVE: To examine the associations between life satisfaction, loneliness,
      general health and depression among 172 medical students in Malaysia. METHOD:
      Participants completed a questionnaire battery, which included the 12-item
      General Health Questionnaire, Beck's Depression Inventory, the Revised UCLA
      Loneliness Scale and the Satisfaction With Life Scale. RESULTS: Life satisfaction
      was negatively and significantly correlated with suicidal attitudes, loneliness
      and depression; and positively with health, which was negatively and
      significantly correlated with depression and loneliness. Self-concept was
      negatively correlated with loneliness and depression, depression was positively
      and significantly correlated with loneliness. Mediational analyses showed that
      the effects of loneliness and life dissatisfaction on depression were fully
      mediated by health. CONCLUSION: Even though less satisfied, and particularly
      lonelier, individuals are more likely to report higher levels of depression, this
      is only the case because both higher loneliness and life dissatisfaction are
      associated with poorer health. These results are discussed in terms of their
      implications for the diagnosis and treatment of mental health disorders in
      developing nations.

PMID- 17180632
TI  - Laparoscopic repair of Morgagni hernia.
AB  - BACKGROUND: Foramen of Morgagni hernias are rare diaphragmatic hernias. They
      account for 3-5% of all diaphragmatic hernias and the majority of the cases are
      asymptomatic. They are caused by trauma, obesity or pregnancy. With the
      advancements of laparoscopic surgery, laparoscopic repair has become an excellent
      alternative to open repair for Morgagni hernias. We report five cases of Morgagni
      hernia repaired with the laparoscopic approach in conjunction with a review of
      the literature. PATIENTS: A retrospective review comprised five patients who had
      a Morgagni hernia repaired with a laparoscopic approach. Data from these patients
      were collected for the period between February 2001 and May 2005. RESULTS: The
      average age at operation was 61. The anatomic pathology was detected
      preoperatively using X-rays and computerized tomography (CT) scans in four of our
      patients. Hernia was detected incidentally in one patient during an elective
      cholecysectomy. Three hernias were right-sided and two were left-sided. The
      contents of the hernias were omentum and transverse colon in the majority of the
      patients. The hernia was repaired with a laparoscopic approach in all patients.
      Four patients had composite mesh repair and one patient had primary closure with
      nonabsorbable sutures. There were no postoperative complications and all patients
      tolerated laparoscopic repair. There were also no recurrences during follow-up.
      CONCLUSIONS: Laparoscopic repair is a candidate to be a standard treatment for
      Morgagni-type hernias. It is an effective and safe technique and can be performed
      by all compotent general surgeons with a certain learning curve. It has several
      advantages relative to the open operation.

PMID- 17180633
TI  - Superior phrenic artery: an anatomic study.
AB  - The majority of anatomical textbooks offer very little information concerning the
      anatomy and distribution of the superior phrenic artery (SPA). However, in the
      last decade, a number of reports have appeared with reference to the
      transcatheter arterial chemoembolization of the collateral arterial supply of
      hepatic carcinoma (HC). Considering the potential role of the SPA as a source of
      collateral blood supply to HC, the aim of this study was to identify the origin
      and distribution of the SPA. One hundred formalin-fixed adult cadavers with no
      evidence of significant gross diaphragmatic pathology were examined. The right
      SPA originated from the aorta (R1) in 42%, as a branch of the proximal segment of
      the 10th intercostal artery (R2) in 33%, and as a branch of the distal segment of
      the 10th intercostal artery (R3) in 25%, of the specimens. The left SPA
      originated from the aorta (L1) in 51%, from proximal segment of the left 10th
      intercostal artery (L2) in 40%, and from the distal segment of the left 10th
      intercostal artery (L3) in 9%, of the specimens. In types R1, R2, L1 and L2 the
      SPA terminated, after a short course, within the medial and posterosuperior
      surfaces of the thoracic diaphragm and diaphragmatic crura. Conversely, in types
      R3 and L3 the lateral origin of the SPAs confined the ultimate distribution of
      the vessels to the posterior surface of the diaphragm. These findings could
      provide a better understanding of the anatomy and distribution of the arterial
      supply of the diaphragm and the potential involvement of the right SPA as an
      extrahepatic collateral artery developed in HC.

PMID- 17180634
TI  - Three-dimensional CT study on normal anatomical features of atlanto-axial joints.
AB  - It has long been a research hotspot to diagnose atlanto-axial disorder by
      observing the shape and motions of atlanto-axial joints. The basis for
      correlative studies is to ascertain the normal anatomic features of atlanto-axial
      joints. In our study, 33 normal subjects were examined for atlanto-axial joints,
      by three-dimensional CT (3D-CT) in functional positions (neutral, left and right
      rotary position). The contraposition between superior and inferior articular
      facets of lateral atlanto-axial joints (AFLAJ), including its shape and type, the
      width of rotational facets displacement (RFD), head's rotational angle (HRA) and
      rotational angle at C(1-2) (RAC(1-2)) were observed and measured on 3D-CT images.
      In neutral position, a complete contraposition of AFLAJ was found in 25 subjects
      as well as a basic contraposition in 8. In rotary position, the width of RFD was
      between 6.16 and 8.68 mm, the angle of HRA was between 30.2 degrees and 45.8
      degrees , and RAC(1-2) between 26.7 degrees and 38.9 degrees . There is no
      significant difference in RFD, HRA or RAC(1-2) (P > 0.05) in between levorotatory
      and dextrogyrate orientation, and there is a positive correlation between RFD and
      RAC(1-2) (r = 0.5078, P < 0.05). Our study results show that the contraposition
      of AFLAJ can be clearly displayed by 3D-CT, and complete or basic contraposition
      in neutral position and symmetry RFD, HRA and RAC(1-2) in rotary position, are
      the normal anatomic features of atlanto-axial joints.

PMID- 17180635
TI  - Chromosome painting and molecular dating indicate a low rate of chromosomal
      evolution in golden moles (Mammalia, Chrysochloridae).
AB  - Golden moles (Chrysochloridae) are poorly known subterranean mammals endemic to
      Southern Africa that are part of the superordinal clade Afrotheria. Using G
      banding and chromosome painting we provide a comprehensive comparison of the
      karyotypes of five species representing five of the nine recognized genera:
      Amblysomus hottentotus, Chrysochloris asiatica, Chrysospalax trevelyani,
      Cryptochloris zyli and Eremitalpa granti. The species are karyotypically highly
      conserved. In total, only four changes were detected among them. Eremitalpa
      granti has the most derived karyotype with 2n = 26 and differs from the remaining
      species (all of whom have 2n = 30) by one centric and one telomere:telomere
      fusion. In addition, two intrachromosomal rearrangements were detected in A.
      hottentotus. The painting probes also suggest the presence of a unique satellite
      DNA family located on chromosomes 11 and 12 of both C. asiatica and C. zyli. This
      represents a synapomorphy linking these two sympatric species as sister taxa. A
      molecular clock was calibrated adopting a relaxed Bayesian approach for multigene
      data sets comprising publicly available sequences derived from five gene
      fragments representative of three golden moles and 39 other eutherian species.
      The data suggest that golden moles diverged from a common ancestor approximately
      28.5 mya (95% credibility interval = 21.5-36.5 mya). Based on an inferred
      chrysochlorid ancestral karyotype of 2n = 30, the estimated rate of 0.7
      rearrangements per 10 my (95% Credibility Interval = 0.54-0.93) differs from the
      'default rate' of mammalian chromosomal evolution which has been estimated at one
      change per 10 million years, thus placing the Chrysochloridae among the slower
      evolving chromosomal lineages thus far recorded.

PMID- 17180637
TI  - Cross-cultural adaptation of the Behcet's Disease Current Activity Form (BDCAF)
      to Brazilian Portuguese language.
AB  - The Behcet's Disease Current Activity Form (BDCAF) is a clinical instrument used
      to assess the activity of Behcet's disease (BD), which was originally developed
      in English. The aim of the present study was to perform a cross-cultural
      adaptation of the BDCAF to Brazilian Portuguese language and to evaluate its
      reliability in a population of Brazilian patients with BD. Brazilian Portuguese
      version of the BDCAF, named BR-BDCAF, was obtained according to established
      guidelines. Forty Brazilian patients with BD diagnosed according to the
      International Study Group for Behcet's Disease criteria were assessed by two
      rheumatologists in independent sessions and submitted to the BR-BDCAF. Inter- and
      intraobserver agreement were then evaluated by kappa scores (values higher than
      0.6 indicated good agreement). Good inter- and intraobserver agreements were
      achieved for the most common manifestations of BD: kappa scores higher than 0.6
      were obtained for oral and genital ulcerations, skin lesions, and articular and
      general complaints. Moderate interobserver agreement was obtained for ocular
      activity (kappa 0.483) and fair interobserver agreement was obtained for
      gastrointestinal (kappa 0.322), major vessel (kappa 0.281), and central nervous
      system activity (kappa 0.304). BR-BDCAF was found to be a reliable instrument for
      the classic mucocutaneous and articular manifestations of BD and for general
      complaints, but complementary assessment is needed to evaluate specific visceral
      involvement for disease activity.

PMID- 17180636
TI  - Effects of hyaluronan on nitric oxide levels and superoxide dismutase activities
      in synovial fluid in knee osteoarthritis.
AB  - The aim of the present study was to evaluate the effects of hyaluronan (HA) on
      nitric oxide (NO) levels and superoxide dismutase (SOD) enzyme activities in
      synovial fluid (SF) in the treatment of patients with knee osteoarthritis (OA).
      SF samples were aspirated from OA patients before the commencement of the
      treatment (n=23) and 6 weeks after they were treated with HA products. NO levels
      and SOD activities were compared between the pre- and post-treatment of OA
      patients and of the control group (n=10). SF NO levels were significantly higher
      in patients with OA before the commencement of the treatment compared with the
      post-treatment (p<0.001) and the control groups. The SF SOD activity of patients
      before the commencement of the treatment was lower than the values in the
      controls and post-treatment (p<0.001). There is no significant correlation
      between SF NO and SOD levels and the radiographic changes of the OA knee
      according to Kellgren-Lawrence grading (p>0.05). Also, the Western Ontario and
      McMaster Universities Osteoarthritis index (WOMAC) pain scores and physical
      function scores were gradually improved. These findings made us think that SF NO
      was a potent mediator in cartilage damage in OA, whereas SOD was an antioxidant
      mediator in the same process. Exogenous HA injections might reduce the NO levels
      and increase SOD activities in synovial fluid. These effects also do not seem to
      be dependent on the radiographic grading of the OA knee. More comprehensive
      studies are needed to clarify a possible clinical significance of this topic, and
      we suggest that this is an important area for further research into new treatment
      options.

PMID- 17180638
TI  - Tension-free vaginal tape for stress incontinence in women with detrusor
      overactivity.
AB  - In this case report, we discuss two cases of the successful use of the tension
      free vaginal tape (TVT) to treat women with detrusor overactivity (DO) but no
      evidence of urodynamic stress incontinence (USI). The use of the TVT for the
      treatment of DO has been evaluated in a small number of studies of women with
      mixed incontinence. There is no data in the literature concerning its use in
      women with DO only. Here, we briefly review the literature including the
      postulated mechanism by which stress leakage due to DO is cured by the TVT.

PMID- 17180639
TI  - Coping and adjustment in children with cancer: a meta-analytic study.
AB  - The current meta-analysis assessed the efficacy of coping strategies on
      psychological and physical adjustment in children with cancer (n = 1230). Coping
      strategies were operationalized in accordance with two coping taxonomies; the
      first is based on the general orientation of the child's coping attempts
      (approach or avoidance), and the second is based upon coping efforts to regulate
      the stressor and/or feelings of distress attributed to it (problem-focused and
      emotion-focused). Approach, avoidance, and emotion-focused coping were unrelated
      to overall adjustment. A small-to-medium but negative association was found
      between problem-focused coping and adjustment, indicating more use of the
      strategies that compose this dimension are associated with poorer adjustment.
      However, homogeneity analyses also indicated significant variation for all of
      these effect sizes. Follow-up moderator analyses found coping-adjustment
      relations were both dependent upon time since diagnosis and the particular
      stressor the child was dealing with during treatment.

PMID- 17180641
TI  - Travelling waves in two-dimensional smectic-C domains.
AB  - Continued irradiation of smectic-C-like domains of photosensitive Langmuir
      monolayers from azobenzene derivatives induces the nucleation and propagation of
      orientational travelling waves as observed with Brewster angle microscopy (BAM).
      BAM image analysis has allowed to identify different dynamical behaviors
      involving the generation and propagation of such waves. A model based on the
      coupling between an orientational and a composition field proposes a scenario for
      dynamic self-assembly that accounts for most of the observed phenomena, and
      allows to pinpoint the relevance of boundary defects in wave-emitting structures.
      1.

PMID- 17180642
TI  - Citric-acid-coated magnetite nanoparticles for biological applications.
AB  - Water-based magnetic fluids, generally intended for biomedical applications,
      often have various coating molecules that make them stable and compatible with
      biological liquids. Magnetic fluids containing iron oxide particles have been
      prepared by a co-precipitation method, using citric acid as stabilizer. The
      magnetic particles of the magnetic fluids were obtained by chemical precipitation
      from ferric (FeCl(3)) and ferrous salts (FeSO(4) or FeCl(2)) in alkali medium
      (ammonia hydroxide). Citric acid was used to stabilize the magnetic-particle
      suspension. Physical tests were performed in order to determine various
      microstructural and rheological features. Transmission electron microscopy was
      the main investigation method for assessing the magnetic-particle size. The
      dimensional distribution of the magnetic-particle physical diameter was analyzed
      using the box-plot statistical method while infrared absorption spectra were used
      to study the colloidal particle structure. The magnetic-fluid density
      (picnometric method), viscosity (capillary method) and surface tension
      (stalagmometric method) were measured using standard methods.

PMID- 17180643
TI  - [On guidelines for the treatment management].

PMID- 17180644
TI  - [Acute coronary syndrome with and without ST elevation].
AB  - Coronary artery disease accounts for most deaths in western communities. The
      acute coronary syndrome subsidizes ST elevation myocardial infarction, non-ST
      elevation myocardial infarction, and unstable angina pectoris. They are
      characterized by an acute onset of chest pain. The high number of acute coronary
      syndromes of more than 400,000 per year in Germany demonstrates the necessity of
      guidelines. Such guidelines are available from different cardiac societies. The
      implementation of the guidelines of the German Cardiac Society and the European
      Society of Cardiology in the daily clinical practice are demonstrated in this
      review by means of two case presentations. Special attention has been given to
      diagnostic measures, risk stratification, and different therapeutic options. For
      the diagnostic work-up in the acute phase, the ECG and the assessment of cardiac
      biomarkers play the central role. For patients with ST elevation myocardial
      infarction, primary interventional diagnostics and therapy are the first choice.
      For patients presenting with acute coronary syndromes without ST elevation, a
      risk-adapted therapeutic approach should be chosen. High-risk patients (elevated
      troponins, clinical, rhythmologic, and hemodynamic instability, ST depression, or
      diabetes mellitus) should be treated with an early invasive approach within 48-72
      h. Low-risk patients can be treated primarily conservatively. For all patients
      who undergo interventional treatment, administration of an aggressive
      antiaggregatory therapy, including acetylsalicylic acid, clopidogrel,
      glycoprotein IIb/IIIa receptor antagonists, and heparin, is indicated in the
      acute phase. In the chronic phase, an adequate treatment of cardiovascular risk
      factors is of paramount importance.

PMID- 17180640
TI  - The fear-avoidance model of musculoskeletal pain: current state of scientific
      evidence.
AB  - Research studies focusing on the fear-avoidance model have expanded considerably
      since the review by Vlaeyen and Linton (Vlaeyen J. W. S. & Linton, S. J. (2000).
      Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of
      the art. Pain, 85(3), 317--332). The fear-avoidance model is a cognitive
      behavioral account that explains why a minority of acute low back pain sufferers
      develop a chronic pain problem. This paper reviews the current state of
      scientific evidence for the individual components of the model: pain severity,
      pain catastrophizing, attention to pain, escape/avoidance behavior, disability,
      disuse, and vulnerabilities. Furthermore, support for the contribution of pain
      related fear in the inception of low back pain, the development of chronic low
      back pain from an acute episode, and the maintenance of enduring pain, will be
      highlighted. Finally, available evidence on recent clinical applications is
      provided, and unresolved issues that need further exploration are discussed.

PMID- 17180645
TI  - [Chronic stable angina pectoris. A comparison of diagnostic pathways].
AB  - Against the background of a variety of international guidelines and a national
      disease management program for patients with coronary heart disease, a national
      health-care guideline for the management of patients with chronic ischemic heart
      disease ("Nationale VersorgungsLeitlinie Chronische KHK [NVL KHK]") was first
      published in Germany in 2006. This guideline is an interdisciplinary initiative
      of several German health-care authorities and medical societies. Because of the
      limited diagnostic sensitivity of about 70% only, and a high percentage of
      patients, who are unable to exercise, a negative stress ECG can definitely not
      exclude hemodynamically significant coronary heart disease. Therefore, the well
      known evidence-based algorithms of the American College of Cardiology/American
      Heart Association (ACC/AHA) guidelines for noninvasive stress testing and
      complementary stress imaging were newly adopted by the NVL KHK. In flow charts
      for patients with suspected or already known chronic ischemic heart disease, the
      essential importance of stress imaging is depicted on different levels of
      decision. Stress imaging methods considered comparable and interchangeable are:
      stress echocardiography combined with physical or pharmacological stress testing,
      myocardial perfusion imaging with physical or pharmacological stress testing,
      dobutamine stress magnetic resonance imaging (DSMR), or myocardial perfusion
      magnetic resonance tomography (MRT). Basically, no stress imaging method is
      definitely superior to the others, each method has its own advantages and
      disadvantages that should be considered and adjusted to the individual patient.
      Moreover, the NVL KHK gives the recommendation that with the decision for one
      method also the local availability and institutional expertise of diagnostic
      centers should be taken into account. However, according to the Bayes theorem,
      stress imaging combined with physical or pharmacological stress testing is only
      indicated in patients with an intermediate pretest probability for chronic
      ischemic heart disease between 10% and 90%. However, the assessment of the
      pretest probability is difficult or impossible in totally asymptomatic patients
      with suspected chronic ischemic heart disease. This is exemplified by a typical
      case report.

PMID- 17180646
TI  - [The European Society of Cardiology (ESC) guidelines for percutaneous coronary
      interventions (PCI). Three case reports].
AB  - The European Society of Cardiology (ESC) for the first time issued guidelines for
      percutaneous coronary interventions (PCI) in spring 2005. The strengths of
      recommendations stated in the ESC guidelines (as in those of the AHA/ACC
      [American Heart Association/American College of Cardiology]) are traditionally a
      combination of recommendation classes (I, IIa, and IIb) and a level of evidence
      (A, B, or C). This paper explains and discusses selected focal points of the ESC
      PCI guidelines based on three representative cases from daily practice. 1. Stable
      coronary artery disease (CAD): PCI in a 53-year-old patient without angina
      pectoris and proof of myocardial ischemia. With a clear indication of ischemia in
      the anterior myocardial wall, the ESC PCI guidelines indicated coronary
      angiography with possible PCI, even without angina pectoris symptoms. Cardiac
      catheterization showed a 99% proximal LAD stenosis, which was immediately dilated
      and stented based on the indicated ischemia. According to the ESC PCI guidelines,
      an intervention is indicated for CAD when a larger ischemic area is clearly
      evident even in the absence of typical angina (recommendation class I A). 2. ST
      segment elevation myocardial infarction (STEMI): PCI even after successful
      thrombolysis. A 70-year-old patient experienced acute substernal pain and
      immediately went to his nearby hospital. The ECG clearly showed anterior
      myocardial wall STEMI, which in this hospital without a cardiac cath lab
      indicated thrombolysis, since it could be initiated within 3 h after the onset of
      chest pain. Pain relief was evident soon after thrombolysis, combined with a
      resolution of the ST segment elevations. As suggested by the ESC PCI guidelines,
      a transfer to a cardiac cath lab took place the next day, where the 50% residual
      stenosis of the LAD was stented. The ESC PCI guidelines suggest coronary
      angiography with possible PCI within 1-2 days following successful thrombolysis
      (recommendation class I A). Thus, even "successful" thrombolysis is not regarded
      as the final treatment for STEMI. 3. Premature termination of clopidogrel after
      stent implantation: stent thrombosis with acute myocardial infarction. A 46-year
      old patient visited the practice due to increasing dyspnea. 4 months earlier, a
      Taxus stent had been implanted at a heart center into the second RPLS of the RCX;
      3 days later, a Cypher stent was implanted in the LAD. Upon being discharged on a
      Friday at noon, the patient was advised to see his general practitioner soon to
      attain a prescription for clopidogrel. The patient was given an appointment at
      his general practitioner for the following Wednesday afternoon. But on that
      Wednesday morning the patient went into cardiogenic shock. Although the occluded
      LAD (stent thrombosis) could be quickly reopened, left ventricular myocardium
      became severely damaged. Until a cardiac transplantation will be performed, a
      defibrillator was implanted. This "organizational" gap in clopidogrel
      administration did not conform to the ESC PCI guidelines: after implantation of
      any coronary stent, dual antiplatelet treatment (acetylsalicylic acid and
      clopidogrel) must be consistently administered for at least 4 weeks. After
      implantation of drug-eluting stents (DES), the ESC PCI guidelines call for
      clopidogrel administration for at least 6 months; when small vessels, long
      lesions or a complex anatomy (e. g., bifurcation stenting) are involved, a
      duration of 1 year or even longer is recommended. The optimal duration of
      platelet aggregation inhibition following PCI with DES of unprotected left main
      stem stenoses is unknown at this time. The traditional levels of evidence
      according to ESC, AHA and ACC criteria (levels A, B, or C) do no longer meet the
      actual requirements to assess the scientific evidence of randomized PCI trials
      and registry studies. For example, only two small randomized studies with few
      patients and insufficient statistical power utilizing a clinically insignificant
      surrogate endpoint would be enough to attain level of evidence A. Consequently, a
      new scoring system will be proposed, which considers criteria such as the
      importance of a primary clinical endpoint, the statistical power achieved, and
      the presence of an independent external data review and safety monitoring board.

PMID- 17180648
TI  - [Sudden cardiac death, ICD and resynchronization therapy].
AB  - The guidelines for the implantation of cardioverter defibrillators recommend the
      primary prevention of sudden cardiac death based on the results of MADIT II,
      Companion and SCD-HeFT. The main risk factors for ventricular arrhythmias are
      previous myocardial infarction, depressed left ventricular function, and chronic
      heart failure. The presented case reports demonstrate the indication for a
      defibrillator or biventricular defibrillator as a basis of clinical pathways.

PMID- 17180647
TI  - Management of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting an
      estimated 4.5 million people within the European Union. Indeed, the prevalence of
      AF continues to rise, in view of the aging population and the better management
      of heart attacks, making it the new "epidemic". Irrespective of a rate control or
      rhythm control strategy, appropriate antithrombotic therapy is central to AF
      management, by reducing the risk of stroke and thromboembolism. This overview
      focuses on the management of AF, with reference to recently published guidelines
      and describes their application in clinical practice using three clinical case
      scenarios.

PMID- 17180649
TI  - [Infective endocarditis. A case report as mirror of the guidelines].
AB  - Even today, in times of modern antibiotic therapy, infective endocarditis is a
      disease with a high mortality which is difficult to diagnose and to treat. The
      changing clinical face of this disease in the last decades results from a
      changing predisposition of the patients, an increasing age, and is accompanied
      with shift from streptococci toward staphylococci as the main causative
      microorganisms. Evidence from randomized trials is limited due to a low incidence
      of the disease. Thus, application of the guidelines for diagnosis and treatment
      on a patient has always to respect the individual history, and the individual
      clinical course. The authors describe and comment the case of a patient with
      endocarditis of the native aortic valve due to S. epidermidis from diagnosis to
      discharge from the hospital following the current German guidelines for diagnosis
      and treatment of infective endocarditis.

PMID- 17180650
TI  - Midventricular obstruction and clinical decision-making in obstructive
      hypertrophic cardiomyopathy.
AB  - The presence of intraventricular obstruction is a powerful predictor of outcome
      in patients with hypertrophic cardiomyopathy (HCM) and, when associated with
      severe, drug-refractory symptoms, should be managed aggressively. Resting left
      ventricular outflow obstruction is found in approximately 20% of the patients,
      classically occurs at the subaortic level, and is associated with mitral valve
      systolic anterior motion (SAM). In a minority of patients, however, the impedance
      to flow occurs at midventricular level, unrelated to SAM. Symptomatic
      midventricular obstruction represents a clinical challenge, and its treatment is
      not standardized. In these patients, both surgical myectomy and alcohol septal
      ablation (ASA) are technically feasible. A rational approach to the management of
      these patients depends on accurate characterization of the pathophysiology,
      coupled with comparison of the results of different management strategies. To
      illustrate these points, the details of a patient who first underwent
      percutaneous ASA and subsequently required redo surgical treatment are described
      here, with special emphasis on the implications to the management of
      midventricular obstruction, as well as to the more global issue of obstructive
      HCM.

PMID- 17180651
TI  - Diagnostic and therapeutic algorithms in chronic heart failure.
AB  - The Treatment of chronic heart failure (CHF) has improved markedly over the last
      10-15 years. Mortality and morbidity have been reduced significantly. However,
      CHF is still associated with a high mortality and is costly due to the need for
      hospitalization of many patients. The best management of patients with CHF
      includes correct diagnosis and risk assessment, symptomatic treatment of fluid
      retention, if present, and a combination of at least two neurohormonal
      antagonists to improve prognosis. Optimal practice in most organizations needs a
      structured approach to the management. In order to achieve this optimal
      management, guidelines are used to harmonize and encourage implementation of
      treatments. Guidelines from Europe and North America are harmonized as they are
      based on the same evidence. However, in some important aspects there can be
      differences in the interpretation of the evidence. A comparison of four major
      guideline documents was published recently.

PMID- 17180652
TI  - Management of patients with suspected (peri-)myocarditis and inflammatory dilated
      cardiomyopathy.
AB  - Inflammatory cardiomyopathy and myocarditis are considered acquired forms of
      dilated cardiomyopathy. Whereas consensus documents on the diagnosis of
      myocarditis and perimyocarditis do exist, guidelines on the specific treatment
      have been established only for the management of pericardial diseases, which at
      least partly can be applied in analogy to myocarditis. Presently, feasible
      clinical pathways are available, which can lead to a correct diagnosis and
      specific treatment. This is illustrated with two cases of fulminant myocarditis,
      in one with successful diagnosis and treatment of a cardiac sarcoid and another
      one in which diagnostic nihilism led to a lethal outcome in giant cell
      myocarditis at necropsy. A case of active parvo B19-positive myocarditis
      demonstrates the role of immunoglobulin treatment under these conditions.

PMID- 17180653
TI  - Management strategies in pericardial emergencies.
AB  - BACKGROUND: The most frequent pericardial emergency is cardiac tamponade, but
      complications of an acute coronary syndrome and aortic dissection may also
      involve the pericardium. Acute pericarditis can also represent a medical
      emergency due to chest pain of upsetting intensity. Decompensations in chronic
      advanced constriction and in the clinical course of purulent pericarditis
      necessitate critical care as well. DIAGNOSIS AND MANAGEMENT: The diagnosis of
      cardiac tamponade is based on clinical presentation and physical findings,
      confirmed by echocardiography and cardiac catheterization. Tamponade is an
      absolute indication for urgent drainage, either by pericardiocentesis or surgical
      pericardiotomy. The approach for pericardiocentesis can be subxiphoid or
      intercostal using echocardiographic or fluoroscopic guidance. Urgent drainage,
      combined with intravenous antibiotics, is also mandatory in suspected purulent
      pericarditis. If confirmed, it should be combined with intrapericardial rinsing
      (best by a surgical drainage). Pericardiocentesis is contraindicated in cardiac
      tamponade complicating aortic dissection. This condition should immediately lead
      to cardiac surgery. Although pericardiectomy is the only treatment for permanent
      constriction, this procedure is contraindicated when extensive myocardial
      fibrosis and/or atrophy are demonstrated. CASE STUDY: Iatrogenic tamponade may
      occur during percutaneous mitral valvuloplasty, implantation of pacemakers,
      electrophysiology and radiofrequency ablation procedures, right ventricular
      endomyocardial biopsy, percutaneous coronary interventions, and rarely during
      Swan-Ganz catheterization. The authors report on a 79-year-old who suffered
      coronary perforation and cardiac tamponade during elective stent implantation.
      Tamponade was successfully treated with pericardiocentesis and implantation of a
      membrane-covered graft stent. Subsequent recurrent pericarditis/postpericardial
      injury syndrome with moderate pericardial effusion was initially treated with
      aspirin and then with aspirin and colchicine. At 6 months, the patient is in
      stable remission even after withdrawal of colchicine. CONCLUSION: Natural history
      of pericardial diseases can be complicated with pericardial emergencies requiring
      prompt diagnosis, intensive care with hemodynamic monitoring, and early
      aggressive management. Medical supportive measures, drainage of pericardial
      effusion, surgical pericardiotomy, and pericardiectomy should be applied when
      needed with no delay. This procedural approach also applies to iatrogenic
      interventions leading to tamponade.

PMID- 17180654
TI  - [Syncope].
AB  - Syncope is a transient, self-limiting loss of consciousness usually leading to a
      fall. The onset of syncope is relatively rapid and the subsequent recovery is
      spontaneous, complete and usually prompt. As syncope is a symptom, the aim of the
      diagnostic work-up is to assess whether there is a syncope or another
      "nonsyncopal" condition, whether there are clinical features suggesting the
      diagnosis, whether the patient has an increased risk for mortality or recurrent
      episodes, and whether the patient must be admitted to hospital. The diagnostic
      work-up is given for two cases: a 68-year-old male with insulin-dependent
      diabetes experienced his first syncope after lunch. The clinical judgment
      suggested a neurocardiogenic syncope. The initial evaluation consisting of
      history, physical examination and twelve-lead ECG evidenced that the patient
      received several drugs for arterial hypertension so that an orthostatic
      hypotension had to be ruled out. The twelve-lead ECG showed a left bundle branch
      block suggesting an arrhythmic syncope and the need for additional diagnostics:
      an echocardiography mainly to assess the left ventricular function which was
      normal, and a 24-h long-term ECG to rule out arrhythmias which were not observed.
      The patient gets an explanation of his risk and the reassurance about his
      excellent prognosis and some preventive lifestyle modifications such as
      sufficient volume intake. The second case is a sick 58-year-old male with
      tracheal cough und aggravating breathing who had a syncope on his way to the
      toilette. The cause of the syncope was related to a bronchitis with high fever.
      The patient received a causative treatment and recovered completely.

PMID- 17180655
TI  - Congestive heart failure: a diagnostic approach in cardiac amyloidosis. Role for
      cardiac magnetic resonance imaging.

PMID- 17180656
TI  - Strong expression of a longevity-related protein, SIRT1, in Bowen's disease.
AB  - The class III histone deacetylase (HDAC), SIRT1, is a mammalian homologue of the
      Saccharomyces cerevisiae chromatin-silencing factor Sir2 that regulates
      longevity. SIRT1 regulates cell survival via deacetylation of p53 and forkhead
      transcription factors, and overexpression of SIRT1 is reported to be essential
      for cell growth and survival in some kinds of cancer. To elucidate the role of
      SIRT1 in human skin carcinogenesis, we have examined SIRT1 protein expression in
      20 cases each of squamous cell carcinoma (SCC), basal cell carcinoma (BCC),
      Bowen's disease (BD), and actinic keratosis (AK) by immunohistochemical analysis.
      Overexpression of SIRT1 is frequently observed in all kinds of non-melanoma skin
      cancers included in this study. In particular, strong expression was observed in
      all cases of BD. In addition, no obvious difference between AK and SCC was
      observed in the expression of SIRT1, suggesting that overexpression of SIRT1 may
      have some relevance to the early stage of skin carcinogenesis. We suppose that
      SIRT1 could be one of the critical targets for future therapy with the aim of
      inhibiting cell proliferation and promoting apoptosis in non-melanoma skin
      cancers.

PMID- 17180658
TI  - Complicated giant polycystic ovary mimicking tumor: MR imaging findings.
AB  - A previously healthy 14-year-old girl presented with a 1-year history of
      abdominal pain that had worsened during the past 4 days. She had a right lower
      abdominal mass that was initially diagnosed as an ovarian tumor. MR imaging
      revealed a unilaterally enlarged and partially torted left polycystic ovary.
      Polycystic ovary is a common cause of increased ovarian volume in women of
      reproductive age. It is characterized by numerous small peripherally located
      follicles and increased stroma. It may mimic a neoplasm and lead to difficulties
      in diagnosis. In this case report, we discuss the unusual MR imaging findings and
      the pitfalls in diagnosis.

PMID- 17180657
TI  - Accuracy of ultrasonography for the diagnosis of intussusception in infants in
      Vietnam.
AB  - BACKGROUND: Intussusception (IS) is the most common cause of acute bowel
      obstruction in infants and young children. Ultrasonography is being increasingly
      used as the primary investigation for the diagnosis of IS and to guide air or
      hydrostatic enema reduction. However the accuracy of ultrasonography outside
      tertiary care settings in developed countries has not been assessed, particularly
      in Asia where the incidence of IS based on sonographic diagnosis has been
      reported as the highest in the world. OBJECTIVE: The aim of this study was to
      evaluate the accuracy of ultrasonography in the diagnosis of acute IS in infants
      less than 2 years of age in a paediatric hospital in Vietnam. MATERIALS AND
      METHODS: A prospective study was conducted at the National Hospital for
      Paediatrics, Hanoi, Vietnam, over a 14-month period recruiting patients <2 years
      of age with IS. Abdominal ultrasonography was performed on each patient and the
      accuracy of the diagnosis was evaluated against the final diagnosis provided by
      air enema and/or surgery. RESULTS: A total of 640 infants <2 years of age
      presented with clinical symptoms and signs of IS. The diagnosis was confirmed in
      533 patients via air enema or surgery. Abdominal ultrasonography was 97.5%
      (466/478) sensitive and 99% (106/107) specific in the detection of IS.
      CONCLUSION: Ultrasonography is an accurate, safe and valuable clinical tool in
      the diagnosis of IS. The use of ultrasonography as a primary investigation for
      patients with suspected IS prevents unnecessary radiological or surgical
      procedures being performed, and reduces radiation exposure while maintaining a
      high level of diagnostic accuracy. These results validate the use of
      ultrasonography for the diagnosis of IS in a developing country setting.

PMID- 17180659
TI  - Integrated PET/CT as a first-line re-staging modality in patients with suspected
      recurrence of ovarian cancer.
AB  - PURPOSE: The aims of this study were to compare CT with PET/CT results in
      patients with suspected ovarian cancer recurrence and to assess the impact of the
      PET/CT findings on their clinical management. METHODS: Thirty-two consecutive
      patients with suspected ovarian cancer recurrence were retrospectively included
      in the study. Abdominal contrast-enhanced CT and PET/CT with [(18)F]FDG, in
      addition to conventional follow-up, were performed in all 32 patients. After the
      comparison between CT and PET/CT results, based on clinical reports, changes in
      the clinical management of patients (intermodality changes) due to PET/CT
      information were analysed. RESULTS: Twenty of the 32 patients were positive at CT
      (62.5%) versus 29 (90.6%) at PET/CT. Intermodality changes in management, i.e.
      use of a different treatment modality, after PET/CT examination were indicated in
      14/32 (44%) patients. In particular, before PET/CT study, the planned management
      was as follows: wait-and-see in 7/32 (22%), further instrumental examinations in
      4/32 (12%), chemotherapy in 10/32 (31%), diagnostic surgical treatment in 6/32
      (19%) and surgical treatment in the remaining 5/32 (16%). After PET/CT study,
      wait-and-see was indicated in 1/32 (3%), further instrumental examinations in
      7/32 (22%), chemotherapy in 16/32 (50%), diagnostic surgical treatment in 2/32
      (6%) and surgical treatment in the remaining 6/32 (19%). CONCLUSION: Integrated
      PET/CT could detect tumour relapse in a higher percentage of patients than could
      CT. A change in the clinical management was observed in 44% of cases when PET/CT
      information was added to conventional follow-up findings.

PMID- 17180660
TI  - Comparison of the prognostic value of SPECT after nitrate administration and
      metabolic imaging by PET in patients with ischaemic left ventricular dysfunction.
AB  - PURPOSE: We compared the prognostic value of 99mTc-tetrofosmin single-photon
      emission computed tomography (SPECT) after nitrate administration and positron
      emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with
      ischaemic left ventricular (LV) dysfunction. METHODS: Eighty-nine patients with
      previous myocardial infarction and LV dysfunction (LV ejection fraction 33 +/-
      10%) underwent 99mTc-tetrofosmin SPECT under control conditions (baseline) and
      after sublingual administration of 10 mg of isosorbide dinitrate (nitrate).
      Within 1 week, all patients underwent PET imaging with 18F-FDG. Four patients
      were excluded because of inadequate FDG uptake caused by severe diabetes. Follow
      up data were obtained by phone contact with patients and by review of hospital or
      physicians' records. Cardiac death, myocardial infarction and late
      revascularisation for unstable angina were considered as events. Follow-up data
      were not available in three patients. Follow-up was 96% complete at a mean period
      of 29 +/- 19 months. RESULTS: At baseline SPECT, 59 (72%) patients had evidence
      of viable myocardium, while 23 did not. Of these latter patients, 12 (52%)
      demonstrated viable myocardium after nitrate and 13 (56%) had preserved metabolic
      activity. Cardiac events (cardiac death, myocardial infarction and late
      revascularisation for unstable angina) occurred in 24 (29%) patients. Event-free
      survival was similar in patients with and patients without viable myocardium at
      baseline SPECT (p = 0.8). In contrast, event-free survival was lower in patients
      with viable myocardium at nitrate SPECT and PET compared to those without viable
      myocardium (both p<0.05). CONCLUSION: In patients with ischaemic LV dysfunction,
      the prognostic value of SPECT imaging after nitrate is comparable to that of PET
      metabolic imaging.

PMID- 17180661
TI  - Effects of an increase in summer precipitation on leaf, soil, and ecosystem
      fluxes of CO2 and H2O in a sotol grassland in Big Bend National Park, Texas.
AB  - Global climate models predict that in the next century precipitation in desert
      regions of the USA will increase, which is anticipated to affect
      biosphere/atmosphere exchanges of both CO(2) and H(2)O. In a sotol grassland
      ecosystem in the Chihuahuan Desert at Big Bend National Park, we measured the
      response of leaf-level fluxes of CO(2) and H(2)O 1 day before and up to 7 days
      after three supplemental precipitation pulses in the summer (June, July, and
      August 2004). In addition, the responses of leaf, soil, and ecosystem fluxes of
      CO(2) and H(2)O to these precipitation pulses were also evaluated in September, 1
      month after the final seasonal supplemental watering event. We found that plant
      carbon fixation responded positively to supplemental precipitation throughout the
      summer. Both shrubs and grasses in watered plots had increased rates of
      photosynthesis following pulses in June and July. In September, only grasses in
      watered plots had higher rates of photosynthesis than plants in the control
      plots. Soil respiration decreased in supplementally watered plots at the end of
      the summer. Due to these increased rates of photosynthesis in grasses and
      decreased rates of daytime soil respiration, watered ecosystems were a sink for
      carbon in September, assimilating on average 31 mmol CO(2) m(-2) s(-1) ground
      area day(-1). As a result of a 25% increase in summer precipitation, watered
      plots fixed eightfold more CO(2) during a 24-h period than control plots. In June
      and July, there were greater rates of transpiration for both grasses and shrubs
      in the watered plots. In September, similar rates of transpiration and soil water
      evaporation led to no observed treatment differences in ecosystem
      evapotranspiration, even though grasses transpired significantly more than
      shrubs. In summary, greater amounts of summer precipitation may lead to short
      term increased carbon uptake by this sotol grassland ecosystem.

PMID- 17180662
TI  - The narrow-leaf syndrome: a functional and evolutionary approach to the form of
      fog-harvesting rosette plants.
AB  - Plants that use fog as an important water-source frequently have a rosette growth
      habit. The performance of this morphology in relation to fog interception has not
      been studied. Some first-principles from physics predict that narrow leaves,
      together with other ancillary traits (large number and high flexibility of
      leaves, caudices, and/or epiphytism) which constitute the "narrow-leaf syndrome"
      should increase fog-interception efficiency. This was tested using aluminum
      models of rosettes that differed in leaf length, width and number and were
      exposed to artificial fog. The results were validated using seven species of
      Tillandsia and four species of xerophytic rosettes. The total amount of fog
      intercepted in rosette plants increased with total leaf area, while narrow leaves
      maximized interception efficiency (measured as interception per unit area). The
      number of leaves in the rosettes is physically constrained because wide-leafed
      plants can only have a few blades. At the limits of this constraint, net fog
      interception was independent of leaf form, but interception efficiency was
      maximized by large numbers of narrow leaves. Atmospheric Tillandsia species show
      the narrow-leaf syndrome. Their fog interception efficiencies were correlated to
      the ones predicted from aluminum-model data. In the larger xerophytic rosette
      species, the interception efficiency was greatest in plants showing the narrow
      leaf syndrome. The adaptation to fog-harvesting in several narrow-leaved rosettes
      was tested for evolutionary convergence in 30 xerophytic rosette species using a
      comparative method. There was a significant evolutionary tendency towards the
      development of the narrow-leaf syndrome the closer the species grew to areas
      where fog is frequently available. This study establishes convergence in a very
      wide group of plants encompassing genera as contrasting as Tillandsia and Agave
      as a result of their dependence on fog.

PMID- 17180663
TI  - Enhancement of juvenile Caribbean spiny lobsters: an evaluation of changes in
      multiple response variables with the addition of large artificial shelters.
AB  - Shortage of natural crevice shelters may produce population bottlenecks in
      juvenile Caribbean spiny lobsters (Panulirus argus), a socially gregarious
      species. We conducted a field experiment to test enhancement of a local
      population of juvenile P. argus with the addition of artificial shelters
      ("casitas") that mimic large crevices (1.1 m(2) in surface area and 3.8 cm in
      height). Changes in density and biomass of juvenile lobsters 15-50 mm carapace
      length (CL) were assessed with a multiple before-after control-impact (MBACI)
      analysis. Separate analyses were also conducted on small (15-35 mm CL) and large
      (35.1-50 mm CL) juveniles to assess size-related effects. First, we carried out
      13 lobster surveys on nine fixed 1-ha sites over a shallow reef lagoon ("before"
      period). Then, we deployed ten casitas in each of five sites and left four sites
      as controls, and conducted 22 further surveys ("after" period). Deployment of
      casitas resulted in a sixfold increase in juvenile density (76% contributed by
      small and 24% by large juveniles) and a sevenfold increase in biomass (40 and
      60%, respectively). Capture-recapture results revealed that enhancement was
      achieved not by promoting individual growth but by increasing survival,
      persistence, and foraging ranges of small and large juveniles. Casitas both
      mitigated shortage of natural shelter and increased sociality, allowing for
      cohabitation of smaller, more vulnerable juveniles with larger conspecifics that
      have greater defensive abilities. Casitas may help enhance local populations of
      juvenile P. argus in Caribbean seagrass habitats, typically poor in natural
      crevice shelters. The use of MBACI and the simultaneous assessment of multiple
      interrelated response variables may be a powerful analytical approach to test
      shelter limitation in other species and to examine the function of structural
      habitat in other systems.

PMID- 17180665
TI  - N-Acetylcysteine derivative inhibits procoagulant activity of human islet cells.
AB  - AIMS/HYPOTHESIS: The early loss of beta cells after islet cell transplantation
      has been attributed in part to blood coagulation at the implant site. Tissue
      factor expressed by beta cells and contaminating duct cells is considered to
      activate this process. Here, we investigated the ability of N-acetyl-L-cysteine
      to suppress the in vitro procoagulant activity of duct cells and human islet cell
      preparations. MATERIALS AND METHODS: The effects of Nacystelyn, a salt derivative
      of N-acetyl-L-cysteine, were first assessed on procoagulant activity induced in
      human plasma by recombinant tissue factor, human primary duct cells or human
      islet cell preparations. The influence of Nacystelyn on clot formation, platelet
      counts and D-dimers were measured in a whole blood tubing loop model. Human beta
      cell viability and insulin synthesis after Nacystelyn treatment were assessed to
      exclude cytotoxicity of Nacystelyn. RESULTS: Nacystelyn efficiently inhibited the
      procoagulant activity of human recombinant tissue factor, primary duct cells and
      human islet cell preparations at clinically relevant concentrations without
      cellular toxicity. CONCLUSIONS/INTERPRETATION: Nacystelyn is a pharmaceutical
      candidate to reduce early beta cell loss related to tissue factor-dependent
      coagulation after islet transplantation.

PMID- 17180664
TI  - Serum calcium is independently associated with insulin sensitivity measured with
      euglycaemic-hyperinsulinaemic clamp in a community-based cohort.
AB  - AIMS/HYPOTHESIS: Diabetes mellitus type 2 is associated with altered calcium
      metabolism. Moreover, in diseases with supranormal serum calcium levels, such as
      primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively
      little is known about the relationship between serum calcium concentration and
      the underlying causes of diabetes-insulin resistance and defective insulin
      secretion-in the normocalcaemic general population. MATERIALS AND METHODS: We
      investigated associations between serum calcium concentration and insulin
      sensitivity and secretion in a population-based cohort of elderly men (Uppsala
      Longitudinal Study of Adult Men, n = 961). Insulin sensitivity index (M/I;
      glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed
      using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated
      from the early insulin response (EIR) during an OGTT. RESULTS: In a multivariable
      linear regression model adjusting for BMI, physical activity, smoking,
      consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and
      serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg(
      1) min(-1) (mU/l)(-1) x 100 (0.024 mg kg(-1) min(-1) [pmol/l](-1) x 100) decrease
      in M/I (p = 0.01). The results remained robust in individuals with normal fasting
      glucose, normal glucose tolerance and serum calcium within the normal range (n =
      413, regression coefficient for 1 SD increase -0.45, p = 0.001). Serum calcium
      was not associated with EIR. Dietary intake of calcium was not independently
      associated with insulin sensitivity or EIR. CONCLUSION/INTERPRETATION: Our data
      support the notion that endogenous calcium may be involved early in the
      development of diabetes and that this effect is mediated mainly through effects
      on insulin sensitivity rather than defective insulin secretion. Dietary intake of
      calcium does not seem to influence insulin sensitivity.

PMID- 17180666
TI  - Determination of resveratrol in wine by photochemically induced second-derivative
      fluorescence coupled with liquid-liquid extraction.
AB  - Basic studies on the photochemical behaviour of trans-resveratrol and its
      photoproduct are reported. Photometrically and fluorimetrically calculated
      acidity constants of the former were determined. The usefulness of the
      determination of resveratrol by photochemically induced fluorescence and second
      derivative photochemically induced fluorescence was also examined. The very
      weakly fluorescent trans-resveratrol is converted into a highly fluorescent
      photoproduct by irradiating hydroethanolic solutions of trans-resveratrol
      containing 40% v/v of ethanol for 60 s with intense UV radiation. The
      photoproduct presents excitation and emission maxima centred at 260 nm, and 364
      and 382 nm, respectively. Under these conditions, a linear relationship between
      fluorescence intensity and trans-resveratrol concentration was found between 6.6
      and 66 ng mL-1. Optimum conditions for the extraction of trans-resveratrol from
      an aqueous phase at pH 5.0 with diethylether were a phase ratio (aqueous/organic)
      of 2, a shaking time of 60 s and a buffer concentration of 0.15 mol L-1. An
      extraction recovery of 100% was reached under these conditions. The optimized
      extraction procedure was applied to the analysis of resveratrol in wine samples,
      employing the amplitude between 356 and 364 nm of the second-derivative
      photoinduced emission spectrum as analytical signal. It was found that there is
      not matrix effect and recoveries around 100% were obtained at different
      fortification levels.

PMID- 17180668
TI  - [Comparison between German and Turkish descent in ischemic stroke. Risk factors,
      initial findings, rehabilitative therapy, and social consequences].
AB  - BACKGROUND: Until now no data has been available on possible specific features of
      the Turkish minority in Germany with respect to stroke. PATIENTS AND METHODS: We
      compared 20 Turkish stroke patients with matched German controls analyzing risk
      factors, findings at admission, rehabilitative treatments, and psychosocial
      aspects. RESULTS: In the Turkish group the interval between onset of symptoms and
      admission was longer (532 min vs 255 min, P < 0.01). All other findings during
      acute treatment and rehabilitation were comparable. At follow-up after 22 months,
      the Barthel index was 90 for the Turks and 100 for the Germans. The Turkish
      patients reported more consultations with physicians than their German
      counterparts (68 vs 12 per year, P < 0.01). Scores for quality of life and
      outcome did not differ. The Turkish patients more frequently required care and
      had a higher degree of disability. CONCLUSIONS: Turkish stroke patients have a
      longer time to admission. Risk factors, findings at admission, and treatment in
      the acute phase and rehabilitation are comparable. Several findings point towards
      a different health behavior. These results highlight the need for specific
      education of the Turkish population in Germany.

PMID- 17180667
TI  - Hypoxia-induced genetic instability--a calculated mechanism underlying tumor
      progression.
AB  - The cause of human cancers is imputed to the genetic alterations at nucleotide
      and chromosomal levels of ill-fated cells. It has long been recognized that
      genetic instability-the hallmark of human cancers-is responsible for the cellular
      changes that confer progressive transformation on cancerous cells. How cancer
      cells acquire genetic instability, however, is unclear. We propose that tumor
      development is a result of expansion and progression-two complementary aspects
      that collaborate with the tumor microenvironment-hypoxia in particular, on
      genetic alterations through the induction of genetic instability. In this
      article, we review the recent literature regarding how hypoxia functionally
      impairs various DNA repair pathways resulting in genetic instability and discuss
      the biomedical implications in cancer biology and treatment.

PMID- 17180669
TI  - [Adult-onset neuronal ceroid lipofuscinosis].
AB  - Neuronal ceroid lipofuscinoses are a heterogenous group of genetic progressive
      neurodegenerative disorders. Curative therapeutic strategies are not known. These
      are largely diseases of childhood; adult-onset forms are rare and poorly
      characterized. The classical adult variant is CLN4 (Kufs' disease), in which
      autosomal-recessive and autosomal dominant forms are known. Furthermore the
      "classic infantile" CLN1, caused by a deficiency of the enzyme palmitoylprotein
      thioesterase, may be of adult onset Neuronal ceroid lipofuscinoses in adulthood
      are multifaceted diseases. Their clinical picture is mainly characterized by
      progressive dementia, seizures, and extrapyramidal motor symptoms. In contrast to
      the infantile forms, visual loss is an uncommon feature that appears only in
      adult CLN1 but not CLN4, which may be helpful in clinical differential diagnosis.

PMID- 17180670
TI  - [Maintenance treatment of opiate addicts].
AB  - Maintenance treatment is now the most common treatment of opiate addicts in
      Germany. The principle of maintenance treatment is the administration of an
      opioid in order to suppress withdrawal symptoms and heroin craving. In this
      manner, maintenance treatment successfully reduces heroin abuse and directly
      associated risk behaviour. Only a minority of maintenance patients became opiate
      abstinent (including the maintenance drug). Racemic methadone is the most
      extensively evaluated maintenance drug. A differential indication between medical
      opioids has not been scientifically established. According to the German
      regulations psychosocial support is an obligatory part of maintenance treatment.
      Most opiate addicts suffer from comorbid mental and somatic diseases. Therefore
      psychiatric and somatic treatment is indicated and of proven value.

PMID- 17180671
TI  - Immunotherapy of myeloid leukaemia.
AB  - The treatment of myeloid leukaemia has progressed in recent years with the advent
      of donor leukocyte infusions (DLI), haemopoietic stem cell transplants (HSCTs)
      and targeted therapies. However, relapse has a high associated morbidity rate and
      a method for removing diseased cells in first remission, when a minimal residual
      disease state is achieved and tumour load is low, has the potential to extend
      remission times and prevent relapse especially when used in combination with
      conventional treatments. Acute myeloid leukaemia (AML) and myelodysplastic
      syndrome (MDS) are heterogeneous diseases which lack one common molecular target
      while chronic myeloid leukaemia (CML) patients have experienced prolonged
      remissions through the use of targeted therapies which remove BCR-ABL(+) cells
      effectively in early chronic phase. However, escape mutants have arisen and this
      therapy has little effectivity in the late chronic phase. Here we review the
      immune therapies which are close to or in clinical trials for the myeloid
      leukaemias and describe their potential advantages and disadvantages.

PMID- 17180672
TI  - Identification of putative ancestors of the multidrug-resistant Salmonella
      enterica serovar typhimurium DT104 clone harboring the Salmonella genomic island
      1.
AB  - The origin of multidrug-resistant Salmonella enterica serovar typhimurium (S.
      typhimurium) harboring the Salmonella Genomic Island 1 (SGI1), which was detected
      for the first time in the mid-1980s is unknown. In this study, we performed
      microarray genomotyping of four multidrug-resistant SGI1 positive strains and
      found that unlike the S. typhimurium LT2 strain, the multidrug-resistant strains
      lacked genes STM0517-0529 allowing the utilization of allantoin as a sole
      nitrogen source. We extended this observation by PCR screening of additional 120
      S. typhimurium field strains and found that this locus was absent in all SGI1
      positive and also in 24% of SGI1 negative strains, which were proposed to be the
      original recipients of SGI1. To prove this hypothesis, we compared the STM0517
      0529 negative strains (with or without the SGI1) by PFGE and PCR prophage typing
      and found that 8 out of 11 of the SGI1 negative strains and 17 out of 22 SGI1
      positive strains were of identical PFGE pattern and PCR prophage pattern, while
      this specific pattern was never observed among STM0517-0529 positive strains. We
      therefore propose that a lineage of the S. typhimurium DT104 sensitive strain
      first lost the ability to metabolize allantoin and then acquired SGI1.

PMID- 17180673
TI  - MDCT diagnosis of ileocolic intussusception secondary to an appendiceal mucocele:
      value of multiplanar reformation.
AB  - We describe an extremely rare case of an ileocolic intussusception with an
      appendiceal mucocele as the lead-point and cause of acute right lower quadrant
      pain in an adult patient. There are only few reported cases of this entity in the
      radiologic literature. We describe the multislice (computed tomography) CT
      features and emphasize the value of multiplanar reformations. We also discuss how
      specific findings on CT should allow for a correct preoperative diagnosis.

PMID- 17180674
TI  - Whole body 16-row multislice CT in emergency room: effects of different protocols
      on scanning time, image quality and radiation exposure.
AB  - The objective of this study was to compare two different scanning protocols in
      patients suspected to have multiple trauma using multidetector 16-row computed
      tomography (CT) to better define scanning time, imaging quality and radiation
      exposure. Forty-six patients, between March 2004 and March 2005, with suspected
      multiple trauma (cerebral, spine, chest, abdominal and pelvis) were evaluated
      with two different protocols: Protocol "A" 26 patients; Protocol "B" 20 patients.
      Protocol A consists of a single-pass continuous whole-body acquisition (from
      vertex to pubic symphysis), whereas Protocol B of conventional segmented
      acquisition with scanning of body segments individually. Both protocols were
      performed using a multidetector 16-rows CT (Light-Speed 16, General Electric
      Medical System, Milwaukee, WI, USA) with the same technical factors. Radiation
      dose was evaluated in two ways: computer tomography dose index (CTDI) = dose
      measured in central and peripheral region of the subjects as a direct result of a
      CT section acquisition of T millimeters thick (independent from the two
      protocols) and dose length product (DLP) = total dose deposited over the length
      of the acquisition (dependent from the two protocols). Image quality was rated
      according to the following scores: 1, excellent; 2, good; 3, satisfactory; 4,
      moderate and 5, poor. The results were compared using Wilcoxon's test to identify
      significant difference in terms of image quality, scanning time, radiation
      exposure and presence of artifacts, assuming significance at a p value of <0.05.
      In the single-pass scanning, DLP was 2.671 mGy x cm and a total scan time of 35
      s. In whole-body protocols, we have seen artifacts due to arm adduction in thorax
      and less image quality in brain. In the conventional segmented study, DLP was
      3.217 mGy x cm and a total scan time of 65 s; this protocol offered less
      extraction capabilities of off-axial on focused images of the entire spine,
      aorta, facial bones or hip without rescanning. Protocol A revealed a significant
      decrease in scan time (35 vs 65 min, p < 0.05), time in the CT examination room
      (21.7 vs 31.6 min.; p < 0.05), and final image analysis (83.7 vs 102.9 min; p <
      0.05) and radiation dose compared to protocol B (p < 0.05). No significant
      difference was found for patient transport time, image reconstruction time and
      imaging quality. Reconstruction and isotropic reformation of axial image acquired
      by whole-body, single-pass protocols due to entire spine evaluation, aortic and
      splanchnic CT angiography eliminate additional studies. The whole-body, single
      pass protocols, compared with segmented acquisitions protocols, resulted in a
      reduced total radiation dose without relevant loss of diagnostic image
      information.

PMID- 17180676
TI  - [Automatic guided endoscopy in nasal sinus surgery].

PMID- 17180675
TI  - The cenH3 histone variant defines centromeres in Giardia intestinalis.
AB  - Histone H3 variants play critical roles in the functional specialization of
      chromatin by epigenetically marking centromeric chromatin and transcriptionally
      active or silent genes. Specifically, the cenH3 histone variant acts as the
      primary epigenetic determinant of the site of kinetochore assembly at
      centromeres. Although the function of histone variants is well studied in plants,
      animals, and fungi, there is little knowledge of the evolutionary conservation of
      histone variants and their function in most protists. We find that Giardia
      intestinalis--a diplomonad parasite with two equivalent nuclei--has two
      phylogenetically distinct histone H3 variants with N-terminal extensions and
      nonconserved promoters. To determine their role in chromatin dynamics,
      conventional H3 and the two H3 variants were GFP-tagged, and their subcellular
      location was monitored during interphase and mitosis. We demonstrate that one
      cenH3-like variant has a conserved function in epigenetically marking
      centromeres. The other H3 variant (H3B) has a punctate distribution on
      chromosomes, but does not colocalize with active transcriptional regions as
      indicated by H3K4 methylation. We suggest that H3B could instead mark
      noncentromeric heterochromatin. Giardia is a member of the Diplomonads and
      represents an ancient divergence from metazoans and fungi. We confirm the ancient
      role of histone H3 variants in modulating chromatin architecture, and suggest
      that monocentric chromosomes represent an ancestral chromosome morphology.

PMID- 17180677
TI  - [Sonography aided computer assisted surgery (SACAS) in orbital surgery].
AB  - BACKGROUND: The application of computer assisted procedures in orbital surgery is
      made more difficult by the intraoperative tissue shift in intraorbital
      structures, since this intraoperative dislocation cannot be imaged in
      preoperative CT/MR datasets. METHODS: After preoperative recording of CT and/or
      MR datasets in five patients with orbita affected by frontobasal tumors, we used
      intraoperative sonography by coupling the ultrasound unit to the navigation
      system. RESULTS: Registration, referencing and calibration of the ultrasound
      system proceeded without any difficulties. Intraoperatively, the structures of
      the anterior and middle thirds of the orbita and their tissue shift could be
      particularly well evaluated sonographically. CONCLUSION: The use of navigated
      sonography enables repeated intraoperative re-evaluation of preoperative CT/MR
      datasets. The fusion of intraoperative sonography with preoperative imaging
      visualizes the tissue shift and facilitates the identification of anatomical
      structures and the spatial orientation of the surgeon. This appears to allow both
      increased operative radicality and greater tissue protection. In our opinion, the
      intraoperative parallel application of a non-calibrated ultrasound system and an
      only CT/MRT based navigation system cannot fulfill these requirements because of
      anatomical complexity.

PMID- 17180678
TI  - Fatal fat embolism complicating cemented total knee replacement: another
      manifestation of the metabolic syndrome?
AB  - We report the case of a 52-year-old man who died of massive fat emboli 39 h after
      undergoing elective total knee replacement. His past medical history included
      hypertension, obesity and diabetes (most of the clusters of the metabolic
      syndrome). Post-mortem pathological examination showed fat embolism in the
      kidneys and the brain. This is the first reported case of fat emboli as the cause
      of death in an association with metabolic syndrome, and the case suggests that
      the fat embolism should be anticipated in over weight and obese individuals with
      three or more of the risk factors of the metabolic syndrome.

PMID- 17180679
TI  - ADAM-17 associated with CD44 cleavage and metastasis in oral squamous cell
      carcinoma.
AB  - ADAM-17 (a disintegrin and metalloproteinase 17) is a membrane-anchored protein,
      which can cleave the ectodomain in a variety of transmembrane proteins. In the in
      vitro experiments with tumor cells, ADAM-17 is reported to cleave CD44, an
      adhesion molecule that interacts with hyaluronic acid, to promote tumor cell
      migration. In the present study, we examined ADAM-17 expression and CD44 cleavage
      in specimens from 50 patients diagnosed to have oral squamous cell carcinoma
      (SCC). Each specimen was divided into two pieces, one was studied by
      immunohistochemistry and the other was subjected to a Western blot. By
      coordinating the results of both analyses, ADAM-17 expression was evaluated to be
      high in 23 cases (46%). When CD44 cleavage was also studied by
      immunohistochemical staining as well as with Western blotting, CD44 cleavage was
      judged to be positive in 29 cases (58%). When the ADAM-17 expression level was
      compared with the CD44 cleavage state, most of the cases expressing high levels
      of ADAM-17 (87%) showed positive CD44 cleavage. The level of ADAM-17 expression
      was significantly correlated to the nodal metastasis and local recurrence in oral
      SCC. Our findings suggest that ADAM-17 is involved in CD44 cleavage and
      contributes to tumor progression in oral SCC.

PMID- 17180680
TI  - Comprehensive multi-stage linkage analyses identify a locus for adult height on
      chromosome 3p in a healthy Caucasian population.
AB  - There have been a number of genome-wide linkage studies for adult height in
      recent years. These studies have yielded few well-replicated loci, and none have
      been further confirmed by the identification of associated gene variants. The
      inconsistent results may be attributable to the fact that few studies have
      combined accurate phenotype measures with informative statistical modelling in
      healthy populations. We have performed a multi-stage genome-wide linkage analysis
      for height in 275 adult sibling pairs drawn randomly from the Victorian Family
      Heart Study (VFHS), a healthy population-based Caucasian cohort. Height was
      carefully measured in a standardised fashion on regularly calibrated equipment.
      Following genome-wide identification of a peak Z-score of 3.14 on chromosome 3 at
      69 cM, we performed a fine-mapping analysis of this region in an extended sample
      of 392 two-generation families. We used a number of variance components models
      that incorporated assortative mating and shared environment effects, and we
      observed a peak LOD score of approximately 3.5 at 78 cM in four of the five
      models tested. We also demonstrated that the most prevalent model in the
      literature gave the worst fit, and the lowest LOD score (2.9) demonstrating the
      importance of appropriate modelling. The region identified in this study
      replicates the results of other genome-wide scans of height and bone-related
      phenotypes, strongly suggesting the presence of a gene important in bone growth
      on chromosome 3p. Association analyses of relevant candidate genes should
      identify the genetic variants responsible for the chromosome 3p linkage signal in
      our population.

PMID- 17180681
TI  - Patterns of constitutive and IFN-gamma inducible expression of HLA class II
      molecules in human melanoma cell lines.
AB  - Major histocompatibility complex (MHC) class II proteins (HLA-DR, HLA-DP and HLA
      DQ) play a fundamental role in the regulation of the immune response. The level
      of expression of human leukocyte antigen (HLA) class II antigens is regulated by
      interferon-gamma (IFN-gamma) and depends on the status of class II trans
      activator protein (CIITA), a co-activator of the MHC class II gene promoter. In
      this study, we measured levels of constitutive and IFN-gamma-induced expression
      of MHC class II molecules, analysed the expression of CIITA and investigated the
      association between MHC class II transactivator polymorphism and expression of
      different MHC class II molecules in a large panel of melanoma cell lines obtained
      from the European Searchable Tumour Cell Line Database. Many cell lines showed no
      constitutive expression of HLA-DP, HLA-DQ and HLA-DR and no IFN-gamma-induced
      increase in HLA class II surface expression. However, in some cases, IFN-gamma
      treatment led to enhanced surface expression of HLA-DP and HLA-DR. HLA-DQ was
      less frequently expressed under basal conditions and was less frequently induced
      by IFN-gamma. In these melanoma cell lines, constitutive surface expression of
      HLA-DR and HLA-DP was higher than that of HLA-DQ. In addition, high constitutive
      level of cell surface expression of HLA-DR was correlated with lower inducibility
      of this expression by IFN-gamma. Finally, substitution A-->G in the 5' flanking
      region of CIITA promoter type III was associated with higher expression of
      constitutive HLA-DR (p<0.005). This study yielded a panel of melanoma cell lines
      with different patterns of constitutive and IFN-gamma-induced expression of HLA
      class II that can be used in future studies of the mechanisms of regulation of
      HLA class II expression.

PMID- 17180682
TI  - Localization of the pre-squalene segment of the isoprenoid biosynthetic pathway
      in mammalian peroxisomes.
AB  - Previous studies have indicated that the early steps in the
      isoprenoid/cholesterol biosynthetic pathway occur in peroxisomes. However, the
      role of peroxisomes in cholesterol biosynthesis has recently been questioned in
      several reports concluding that three of the peroxisomal cholesterol biosynthetic
      enzymes, namely mevalonate kinase, phosphomevalonate kinase, and mevalonate
      diphosphate decarboxylase, do not localize to peroxisomes in human cells even
      though they contain consensus peroxisomal targeting signals. We re-investigated
      the subcellular localization of the cholesterol biosynthetic enzymes of the pre
      squalene segment in human cells by using new stable isotopic techniques and data
      computations with isotopomer spectral analysis, in combination with
      immunofluorescence and cell permeabilization techniques. Our present findings
      clearly show and confirm previous studies that the pre-squalene segment of the
      cholesterol biosynthetic pathway is localized to peroxisomes. In addition, our
      data are consistent with the hypothesis that acetyl-CoA derived from peroxisomal
      beta-oxidation of very long-chain fatty acids and medium-chain dicarboxylic acids
      is preferentially channeled to cholesterol synthesis inside the peroxisomes
      without mixing with the cytosolic acetyl-CoA pool.

PMID- 17180683
TI  - Pleomorphic extra-renal manifestation of the glomerular podocyte marker
      podocalyxin in tissues of normal beagle dogs.
AB  - Podocalyxin (PC) was initially identified as a major sialoprotein on the apical
      surface of glomerular podocytes to perform the filtration barrier function.
      Later, it was reported to be expressed in endothelial cells,
      megakaryotes/platelets, and hemangioblasts, the common progenitor cells of the
      hematopoietic and endothelial cells. Recently, increasing numbers of reports have
      indicated that PC is not merely a molecule restricted at renal glomerulus,
      angiogenic or hematopoietic system. To further elucidate the expression pattern
      and address the possible physiological role of PC in adult mammals, we conducted
      an extensive study by immunohistochemistry and immunofluorescence staining on
      various tissues of healthy adult beagle dogs. By combinatory usage of two
      different anti-podocalyxin antibodies recognizing distinct epitopes in PC, we
      have demonstrated that (1) PC is expressed in renal tubules, mesothelium,
      myocardium, striated muscles in tongue, esophagus and extraocular region,
      myoepithelial cells in esophagus and salivary glands, neurons, and ependyma,
      etc.; (2) there are at least three forms of PC proteins, depending upon the
      accessibility of two different PC antibodies, expressed in different
      organs/systems; and (3) a particular form of PC is distributed in a vesicle-like
      compartment in certain organs/systems, such as the central nervous system.

PMID- 17180686
TI  - Posterolateral fusion using laminectomy bone chips in the treatment of lumbar
      spondylolisthesis.
AB  - We retrospectively reviewed the outcome of posterolateral fusion (PLF) in 136
      patients with lumbar spondylolisthesis (LS), who had undergone posterior
      decompression laminectomy with foraminotomy and PLF using laminectomy bone chips
      as bone graft, with reduction of the slipped vertebra with transpedicle screws,
      between 1993 and 2003. Diagnosis of LS was confirmed by plain lumbar radiography,
      with computed tomography (CT) scan or magnetic resonance imaging (MRI) studies
      performed to confirm an associated condition, such as ruptured disc and spinal
      stenosis. The outcome of spinal fusion was good with 129 (94.85%) patients
      attaining solid fusion, while failed fusion was noted in seven (5.15%) patients.
      None of our patients complained of excessive postoperative wound pain.
      Additionally, no complications, such as wound infection, were encountered. Proper
      decortication of the posterior paravertebral gutters with an osteotome and
      removal of all soft tissues from the laminectomy bone chips are significant
      factors contributing to the successful outcome of the laminectomy bone chips in
      PLF. The fusion rate obtained with this type of autogenous bone graft is
      comparable to that of the iliac bone crest autogenous graft; hence, it is a good
      substitute for the iliac crest bone autogenous graft in performing PLF in
      treating lumbar spondylolisthesis.

PMID- 17180685
TI  - Hox gene expression in larval development of the polychaetes Nereis virens and
      Platynereis dumerilii (Annelida, Lophotrochozoa).
AB  - The bilaterian animals are divided into three great branches: the Deuterostomia,
      Ecdysozoa, and Lophotrochozoa. The evolution of developmental mechanisms is less
      studied in the Lophotrochozoa than in the other two clades. We have studied the
      expression of Hox genes during larval development of two lophotrochozoans, the
      polychaete annelids Nereis virens and Platynereis dumerilii. As reported
      previously, the Hox cluster of N. virens consists of at least 11 genes (de Rosa
      R, Grenier JK, Andreeva T, Cook CE, Adoutte A, Akam M, Carroll SB, Balavoine G,
      Nature, 399:772-776, 1999; Andreeva TF, Cook C, Korchagina NM, Akam M, Dondua AK,
      Ontogenez 32:225-233, 2001); we have also cloned nine Hox genes of P. dumerilii.
      Hox genes are mainly expressed in the descendants of the 2d blastomere, which
      form the integument of segments, ventral neural ganglia, pre-pygidial growth
      zone, and the pygidial lobe. Patterns of expression are similar for orthologous
      genes of both nereids. In Nereis, Hox2, and Hox3 are activated before the
      blastopore closure, while Hox1 and Hox4 are activated just after this. Hox5 and
      Post2 are first active during the metatrochophore stage, and Hox7, Lox4, and Lox2
      at the late nectochaete stage only. During larval stages, Hox genes are expressed
      in staggered domains in the developing segments and pygidial lobe. The pattern of
      expression of Hox cluster genes suggests their involvement in the vectorial
      regionalization of the larval body along the antero-posterior axis. Hox gene
      expression in nereids conforms to the canonical patterns postulated for the two
      other evolutionary branches of the Bilateria, the Ecdysozoa and the
      Deuterostomia, thus supporting the evolutionary conservatism of the function of
      Hox genes in development.

PMID- 17180684
TI  - Zebrafish orthopedia (otp) is required for isotocin cell development.
AB  - Several behavioral and physiological processes such as social, sexual, and
      maternal behaviors, learning and memory, and parturition are influenced by the
      neurohypophysial peptide oxytocin. Studies in knockout mice have identified four
      transcriptional regulatory genes that are required for oxytocin neuronal
      development in the hypothalamus. These are the basic helix-loop-helix PAS genes
      Single-minded 1 (Sim1) and Arylhydrocarbon receptor nuclear translocator 2
      (Arnt2), the POU homeobox gene Pou3f2, and the paired homeobox gene Orthopedia
      (Otp). Overall, however, the molecular control of oxytocin cell development is
      poorly understood. Studies in zebrafish provide a complementary view to mouse
      knockout experiments and facilitate understanding of neuroendocrine cell
      development. Isotocin, which is orthologous to oxytocin, is expressed early in
      the developing zebrafish brain. In this paper we show that zebrafish otp mRNA
      expression in the embryonic forebrain is dynamic and complex, and that it
      overlaps with isotocin expression in the dorsal preoptic area. Additionally,
      these studies demonstrate that otp is required for isotocin cell development.
      Evidence is also provided that otp and sim1 function in parallel to direct the
      differentiation of isotocin cells, and that otp is unlikely to affect brain
      patterning. Overall, these studies support the hypothesis that the role of otp in
      zebrafish neuroendocrine cell development is evolutionarily conserved with that
      of mammals.

PMID- 17180687
TI  - A hemicord locomotor network of excitatory interneurons: a simulation study.
AB  - Locomotor burst generation is simulated using a full-scale network model of the
      unilateral excitatory interneuronal population. Earlier small-scale models
      predicted that a population of excitatory neurons would be sufficient to produce
      burst activity, and this has recently been experimentally confirmed. Here we
      simulate the hemicord activity induced under various experimental conditions,
      including pharmacological activation by NMDA and AMPA as well as electrical
      stimulation. The model network comprises a realistic number of cells and synaptic
      connectivity patterns. Using similar distributions of cellular and synaptic
      parameters, as have been estimated experimentally, a large variation in dynamic
      characteristics like firing rates, burst, and cycle durations were seen in single
      cells. On the network level an overall rhythm was generated because the synaptic
      interactions cause partial synchronization within the population. This network
      rhythm not only emerged despite the distributed cellular parameters but relied on
      this variability, in particular, in reproducing variations of the activity during
      the cycle and showing recruitment in interneuronal populations. A slow rhythm
      (0.4-2 Hz) can be induced by tonic activation of NMDA-sensitive channels, which
      are voltage dependent and generate depolarizing plateaus. The rhythm emerges
      through a synchronization of bursts of the individual neurons. A fast rhythm (4
      12 Hz), induced by AMPA, relies on spike synchronization within the population,
      and each burst is composed of single spikes produced by different neurons. The
      dynamic range of the fast rhythm is limited by the ability of the network to
      synchronize oscillations and depends on the strength of synaptic connections and
      the duration of the slow after hyperpolarization. The model network also produces
      prolonged bouts of rhythmic activity in response to brief electrical activations,
      as seen experimentally. The mutual excitation can sustain long-lasting activity
      for a realistic set of synaptic parameters. The bout duration depends on the
      strength of excitatory synaptic connections, the level of persistent
      depolarization, and the influx of Ca(2+) ions and activation of Ca(2+)-dependent
      K(+) current.

PMID- 17180688
TI  - [Introduction to the topic: the science of sleep. Guide to dreaming].

PMID- 17180689
TI  - Xylose transport studies with xylose-utilizing Saccharomyces cerevisiae strains
      expressing heterologous and homologous permeases.
AB  - In the present study, we modified xylose uptake properties of a recombinant
      xylose-utilizing yeast Saccharomyces cerevisiae by expression of heterologous and
      homologous permease-encoding genes. In a mutant yeast strain with the main seven
      hexose transporter genes deleted, and engineered for xylose utilization, we
      screened an expression cDNA library of the filamentous fungus Trichoderma reesei
      (Hypocrea jecorina) for enhanced growth on xylose plates. One cDNA clone with
      significant homology to fungal sugar transporters was obtained, but when the
      clone was retransformed into the host, it did not support significant growth on
      xylose. However, during a long liquid culture of the strain carrying the cDNA
      clone, adaptive mutations apparently occurred in the host, which led to growth on
      xylose but not on glucose. The new transporter homologue, Trxlt1 thus appears to
      code for a protein specific for xylose uptake. In addition, xylose-transporting
      properties of some homologous hexose transporters were studied. All of them,
      i.e., Hxt1, Hxt2, Hxt4, and Hxt7 were capable of xylose uptake. Their affinities
      for xylose varied, K (m) values between 130 and 900 mM were observed. The single
      Hxt strains showed a biphasic growth mode on xylose, alike the Trxlt1 harboring
      strain. The initial, slow growth was followed by a long lag and finally by
      exponential growth.

PMID- 17180690
TI  - Molecular cloning and expression of two new allergens from Anisakis simplex.
AB  - The nematode Anisakis simplex is a marine parasite that causes allergy as well as
      anisakiasis. Although five Anisakis allergens have already been identified,
      immunoblotting studies suggested that unidentified allergens still exist. In this
      study, an expression cDNA library constructed from A. simplex was subjected to
      immunoscreening using an Anisakis-allergic patient serum, and two positive clones
      coding for allergens (named Ani s 5 and 6) were obtained. Ani s 5 (152 amino acid
      residues) is homologous with nematode proteins belonging to the SXP/RAL-2 protein
      family and Ani s 6 (84 amino acid residues) with serine protease inhibitors from
      various animals. Of the 28 patient sera examined, seven and five reacted to
      recombinant Ani s 5 and 6 expressed in Escherichia coli, respectively. By
      inhibition immunoblotting experiments using the recombinant allergens as
      inhibitors, natural Ani s 5 could be identified as a 15-kDa protein in the crude
      extract of A. simplex but natural Ani s 6 could not be identified probably due to
      its low expression. In conclusion, Ani s 5 and 6 are new allergens of A. simplex
      that are specific to some Anisakis-allergic patients.

PMID- 17180692
TI  - [ADANO-Fall Meeting 2006 in Freiburg].

PMID- 17180691
TI  - Fasciola hepatica: ultrastructural effects of a combination of triclabendazole
      and clorsulon against mature fluke.
AB  - A study has been carried out to investigate the ultrastructural effects of
      triclabendazole (TCBZ) at half-normal concentration, clorsulon at half-normal
      concentration, and a combination of these two drugs against mature Fasciola
      hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments.
      Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 microg/ml),
      clorsulon (5 microg/ml), or a combination of the two drugs. For the in vivo
      experiment, rats were dosed with TCBZ (5 mg/kg body weight), clorsulon (5 mg/kg
      body weight), or a combination of the two drugs, and flukes recovered after 48 h.
      Fine structural changes within the tegumental syncytium and tegumental cells were
      assessed by transmission electron microscopy. Treatment with the combination of
      drugs produced greater disruption to the flukes than the individual drugs at half
      normal concentrations, both in vivo and in vitro; also than TCBZ.SO at normal
      concentration in vitro. The changes observed aid in the understanding of the
      gross changes to the tegumental surface described previously (Meaney M, Allister
      J, McKinstry B, McLaughlin K, Brennan GP, Forbes AB, Fairweather I. Parasitol Res
      99:609-621, 2006). The results indicate that there are additive effects between
      TCBZ and clorsulon and suggest that the use of drug combinations would be of
      value in the treatment of TCBZ-resistant fluke.

PMID- 17180693
TI  - [Estimating the prognosis of peripheral facial paralysis: is the minimal nerve
      excitability test still up to date?].
AB  - BACKGROUND: In this retrospective study, we assessed the long-term prognostic
      value of the minimal nerve excitability test (NET) by comparing the results it
      yielded with the House-Brackmann (HB) index in patients with the most common
      types of facial paralysis, Bell's palsy and traumatic facial palsy. PATIENTS AND
      METHODS: Three hundred and fifty patients aged 9-85 years (mean age 42.4 years;
      156 male and 194 female), all of whom were treated initially with the same
      steroid therapy, entered on study. Patients in whom decompression surgery had
      been performed were excluded so as to avoid falsely optimistic prognoses. The 350
      study patients were divided into two groups: group 1 was made up of 250 with
      Bell's palsy and group 2, of 100 with nonpenetrating traumatic facial palsy
      following temporal bone fracture. The NET was conducted repeatedly in all
      patients for 3 weeks from the start of day 3 of treatment, the value recorded on
      day 14 being used in the evaluation. For each patient, the result of the NET was
      recorded as 'normal', 'diminished' or 'without response' according to the
      difference between the two sides of the face. The final HB grading was determined
      after 1 year to check for the agreement between the electrical prognosis and the
      clinical outcome and thus the reliability of the prognosis indicated by the NET.
      RESULTS: The results indicate that a normal NET forecast a satisfactory outcome
      that could be classed as HB I-II in almost all the patients in both groups. Among
      patients who had no response on NET, 85% of those with Bell's palsy and 90% of
      those with traumatic facial palsy failed to recover nerve function. Diminished
      nerve excitability proved to be a sign of a relatively favourable prognosis: 74%
      of patients in each group recovered normal facial function. CONCLUSION: The NET
      is a method of investigation that is easily applied and can make a positive
      contribution to the assessment of prognosis in Bell's palsy and in traumatic
      facial palsy, reflecting the functional state of the facial nerve reliably in
      most of cases.

PMID- 17180694
TI  - [Dorsal nasal mass formation - postrhinoplasty cyst].

PMID- 17180695
TI  - [Homeopathy in acute rhinosinusitis: a double-blind, placebo controlled study
      shows the efficiency and tolerability of a homeopathic combination remedy].
AB  - BACKGROUND: The efficacy and tolerability of a homeopathic combination remedy for
      the treatment of acute rhinosinusitis was investigated. PATIENTS AND METHODS: A
      total of 144 patients with acute rhinosinusitis were treated in a randomized,
      double-blind study either with a homeopathic remedy (n=72) or placebo (n=72). At
      the control examinations after 7, 14 and 21 days, five sinusitis-typical symptoms
      were measured with scores from 0 (absent) to 4 (very strong). The change of sum
      score of the sinusitis-typical symptoms (max. 20 points) during the treatment
      served as the primary efficacy criterion. RESULTS: In the homeopathic treatment
      group, the average sum score dropped from initially 12.1+/-1.6 to 5.9+/-2.0
      points after 7 days. In the placebo group it decreased from 11.7+/-1.6 to 11.0+/
      2.9 points (p<0.0001). The homeopathic treatment resulted in freedom from
      complaints in 90.3% of the patients and improvement in a further 8.3%, whereas in
      the placebo group, the complaints remained unchanged or became worse in 88.9% of
      the patients. Only one adverse event occurred in one patient from the placebo
      group. CONCLUSION: The homeopathic product allows an effective and tolerable
      treatment of acute rhinosinusitis.

PMID- 17180696
TI  - [Cisplatin-induced hearing loss in children in relation to eye color].
AB  - BACKGROUND: Cisplatin is commonly used as a chemotherapeutic agent in the
      treatment of solid tumors. Ototoxicity is an important side-effect. Melanin in
      the inner ear either plays an otoprotective role or has a negative influence on
      hearing. The concentration of cochlear melanin correlates with its concentration
      in the iris. PATIENTS AND METHODS: We retrospectively examined 65 children (37
      males, 28 females, average age 7.5 years) treated with cisplatin at the
      University Clinic of Muenster, Germany. We checked whether their eye color could
      be inferred from the prevalence and extent of cisplatin-induced hearing loss.
      RESULTS: We found a hearing loss of >20 dB in 29 light-eyed and in 21 dark-eyed
      patients. Seven light-eyed and eight dark-eyed patients did not suffer from
      hearing impairment. Using the chi(2)-test on these four parameters, we found no
      significant connection between iris pigmentation and the prevalence or extent of
      hearing loss, although light-eyed children (80.6%) suffered more from hearing
      loss than dark-eyed children (72.4%). After the end of therapy with cisplatin,
      the prevalence of hearing loss was 83.3% in children up to 6 years and 71.4% in
      children older than 6 years. The average cumulative dose of cisplatin was 372
      mg/m(2) of body surface in children with hearing loss, compared to 390 mg/m(2) in
      children without hearing loss. CONCLUSION: We found no significant correlation
      between iris pigmentation (eye color) and hearing loss. Cisplatin-induced hearing
      loss occurs frequently and requires repeated monitoring.

PMID- 17180697
TI  - [Minimally invasive injection therapy in lumbar syndromes].
AB  - Minimally invasive injection therapy is an effective approach for the treatment
      of sciatica with less complications. This therapy is a sufficient option in cases
      without absolute indications for operation.The paper describes in detail the
      different injection techniques like spinal nerve analgesia, epidural
      dorsal/perineural injections, vertebral joint infiltrations, and
      radiculographies.

PMID- 17180698
TI  - Neonatal imitation in chimpanzees (Pan troglodytes) tested with two paradigms.
AB  - Primate species differ in their imitative performance, perhaps reflecting
      differences in imitative capacity. The developmentally earliest form of imitation
      in humans, neonatal imitation, occurs in early interactions with social partners,
      and may be a more accurate index of innate capacity than imitation of actions on
      objects, which requires more cognitive ability. This study assessed imitative
      capacity in five neonatal chimpanzees, within a narrow age range (7-15 days of
      age), by testing responses to facial and vocal actions with two different test
      paradigms (structured and communicative). Imitation of mouth opening was found in
      both paradigms. In the communicative paradigm, significant agreement was found
      between infant actions and demonstrations. Additionally, chimpanzees matched the
      sequence of three actions of the TC model, but only on the second demonstration.
      Newborn chimpanzees matched more modeled actions in the communicative test than
      in the structured paradigm. These performances of chimpanzees, at birth, are in
      agreement with the literature, supporting a conclusion that imitative capacity is
      not unique to the human species. Developmental histories must be more fully
      considered in the cross-species study of imitation, as there is a greater degree
      of innate imitative capacity than previously known. Socialization practices
      interact with innate and developing competencies to determine the outcome of
      imitation tests later in life.

PMID- 17180699
TI  - Do avian brood parasites eavesdrop on heterospecific sexual signals revealing
      host quality? A review of the evidence.
AB  - Eavesdropping can be defined as the extraction of information from the
      interactions between other individuals. It provides a relatively cheap way of
      gathering relevant information for fitness enhancement. Here, we propose that
      obligate avian brood parasites, which always lay their eggs in foreign nests of
      individuals of other species, may eavesdrop on their host sexual signals to
      locate nests of high quality individuals in which to lay their parasitic eggs.
      Sexual signal variation can honestly signal parental quality. Thus, by
      eavesdropping on sexual signals, parasites may select high quality foster parents
      for their own offspring. Such a use of sexual signals within host populations by
      brood parasites differs from signal exploitation theory that proposes that
      parasite only use signals to locate potential host independently from signaller
      quality. Here, we review the avian literature concerning host choice within a
      host species by obligate avian brood parasites and find evidence for host
      selection within individuals of a host species on the basis of cues potentially
      functioning as sexually selected traits, or at least revealing parental
      abilities. We have also found support for the existence of benefits linked to
      host selection by avian brood parasites. Finally, one study reported on the
      attenuation of a sexual ornament in host populations under strong pressure by
      brood parasites. Most of these findings have been interpreted as evidence for
      host selection by avian brood parasites based on the conspicuousness of sexual
      signals. We suggest, however, that these findings may in fact reveal
      eavesdropping on host signalling performance by brood parasites which would use
      the information extracted to choose the better individuals among conspecifics of
      a given host. This provides a new perspective for the study of host selection in
      obligate brood parasites, and raises interesting questions for the study of
      animal cognition that would deserve experimental studies.

PMID- 17180701
TI  - Cyclic AMP-dependent memory mutants are defective in the food choice behavior of
      Drosophila.
AB  - Acute choice behavior in ingesting two different concentrations of sucrose in
      Drosophila is presumed to include learning and memory. Effects on this behavior
      were examined for four mutations that block associative learning (dunce,
      rutabaga, amnesiac, and radish). Three of these mutations cause cyclic AMP
      signaling defects and significantly reduced taste discrimination. The exception
      was radish, which affects neither. Electrophysiological recordings confirmed that
      the sensitivity of taste receptors is almost indistinguishable in all flies,
      whether wild type or mutant. These results suggest that food choice behavior in
      Drosophila involves central nervous learning and memory operating via cyclic AMP
      signaling pathways.

PMID- 17180702
TI  - Resonant neurons and bushcricket behaviour.
AB  - The resonant properties of the intrinsic dynamics of single neurons could play a
      direct role in behaviour. One plausible role is in the recognition of temporal
      patterns, such as that seen in the auditory communication systems of Orthoptera.
      Recent behavioural data from bushcrickets suggests that this behaviour has
      interesting resonance properties, but the underlying mechanism is unknown. Here
      we show that a very simple and general model for neural resonance could directly
      account for the different behavioural responses of bushcrickets to different song
      patterns.

PMID- 17180700
TI  - The histone chaperone Asf1 at the crossroads of chromatin and DNA checkpoint
      pathways.
AB  - Nucleosome assembly involves deposition of a heterotetramer of histones H3/H4
      onto DNA followed by two heterodimers of histones H2A/H2B. Cycles of nucleosome
      assembly and disassembly are essential to cellular events such as replication,
      transcription, and DNA repair. After synthesis in the cytoplasm, histones are
      shuttled into the nucleus where they are associated with chaperone proteins.
      Chaperones of histones H3/H4 include CAF-I, the Hir proteins, and Asf1. CAF-I and
      the Hir proteins function as replication-coupled and replication-independent
      deposition factors for H3/H4, respectively, whereas Asf1 may play a role in both
      pathways. In addition to acting as assembly factors, histone chaperones assist
      nucleosome dissociation from DNA and they may recruit other proteins to
      chromatin. The past few years have witnessed a notable accumulation of genetic,
      biochemical, and structural data on Asf1, which motivated this review. We discuss
      the sequence and structural features of Asf1 before considering its roles in
      nucleosome assembly/disassembly, the cellular response to DNA damage, and the
      regulation of gene expression. We emphasize the key role of Asf1 as a central
      node in a network of partners that place it at the crossroads of chromatin and
      DNA checkpoint pathways.

PMID- 17180705
TI  - Role of gravity-based information on the orientation and localization of the
      perceived body midline.
AB  - The present study focused on the influence of gravity-based information on the
      orientation and localization of the perceived body midline. The orientation was
      investigated by the rolling adjustment of a rod on the subjects' Z-axis and the
      localization by the horizontal adjustment of a visual dot as being straight
      ahead. Experiment 1 investigated the effect of the dissociation between the Z
      axis and the direction of gravity by placing subjects in roll tilt and supine
      postures. In roll tilt, the perception of the body midline orientation was
      deviated in the direction of body tilt and the perception of its localization was
      deviated in the opposite direction. In the supine body orientation, estimates of
      the Z-axis and straight-ahead remained veridical as when the body was upright.
      Experiment 2 highlighted the relative importance of the otolithic and tactile
      information using diffuse pressure stimulation. The estimation of body midline
      orientation was modified contrarily to the estimation of its localization. Thus,
      subjects had no absolute representation of their egocentric space. The main
      hypothesis regarding the dissociation between the orientation and localization of
      the body midline may be related to a difference in the integration of sensory
      information. It can be suggested that the horizontal component of the vestibulo
      ocular reflex (VOR) contributed to the perceived localization of the body
      midline, whereas its orientation was mainly influenced by tactile information.

PMID- 17180707
TI  - Density functional calculations of the properties of silicon-substituted
      hydroxyapatite.
AB  - Ab initio density functional plane-wave calculations are performed on silicon
      substituted hydroxyapatite (SiHA). Formation energies are obtained for the
      substitution of a phosphorus atom by a silicon atom in each of the six phosphate
      groups of the unit cell in turn. It is found that the co-removal of a hydroxyl
      group to maintain charge neutrality is energetically favourable and the
      calculated unit cell volumes for the single silicon substitutions agree extremely
      well with experimental observation. The substitution of a second silicon atom in
      the unit cell is found to be almost as energetically favourable as the first (and
      on one site more favourable) and there can be an attractive interaction between
      the two Si substituents when they are closely separated. However, experimental
      observation suggests that for this concentration of silicon a phase
      transformation to a different structure occurs which, because of the imposed
      boundary conditions, could not be accessed in the calculations. The density of
      states of the SiHA indicates that new states are introduced deep into the valence
      band and the band gap decreases by 1.6 eV compared to phase-pure HA. No new
      states are introduced into the band gap indicating that the Si incorporation does
      not make the material inherently electrically active. Furthermore a population
      analysis shows that the Si impurity has only a small effect on the neighbouring
      ionic charge.

PMID- 17180703
TI  - Homologues of serotonergic central pattern generator neurons in related
      nudibranch molluscs with divergent behaviors.
AB  - Homologues of a neuron that contributes to a species-specific behavior were
      identified and characterized in species lacking that behavior. The nudibranch
      Tritonia diomedea swims by flexing its body dorsally and ventrally. The dorsal
      swim interneurons (DSIs) are components of the central pattern generator (CPG)
      underlying this rhythmic motor pattern and also activate crawling. Homologues of
      the DSIs were identified in six nudibranchs that do not exhibit dorsal-ventral
      swimming: Tochuina tetraquetra, Melibe leonina, Dendronotus iris, D. frondosus,
      Armina californica, and Triopha catalinae. Homology was based upon shared
      features that distinguish the DSIs from all other neurons: (1) serotonin
      immunoreactivity, (2) location in the Cerebral serotonergic posterior (CeSP)
      cluster, and (3) axon projection to the contralateral pedal ganglion. The DSI
      homologues, named CeSP-A neurons, share additional features with the DSIs:
      irregular basal firing, synchronous inputs, electrical coupling, and reciprocal
      inhibition. Unlike the DSIs, the CeSP-A neurons were not rhythmically active in
      response to nerve stimulation. The CeSP-A neurons in Tochuina and Triopha also
      excited homologues of the Tritonia Pd5 neuron, a crawling efferent. Thus, the
      CeSP-A neurons and the DSIs may be part of a conserved network related to
      crawling that may have been co-opted into a rhythmic swim CPG in Tritonia.

PMID- 17180706
TI  - Prevention strategies for type 1 diabetes.
AB  - Type 1 diabetes (T1D) is a common chronic disease of childhood. Patients with T1D
      are at significant risk for developing serious health complications.
      Understanding of the genetics, environmental factors, and natural history of
      diabetes has lead to greater understanding of the etiology and epidemiology of
      T1D. Furthermore, technology has greatly improved glycemic control and reduction
      of complications. However, prevention of the development of diabetes remains
      elusive. This review article describes the past, current and upcoming strategies
      for diabetes prevention for patients at risk for developing autoimmunity, after
      antibody production, and patients with new onset diabetes.

PMID- 17180709
TI  - Interaction of quantitative PCR components with polymeric surfaces.
AB  - This study investigated the effect of exposing a polymerase chain reaction (PCR)
      mixture to capillary tubing of different materials and lengths, at different
      contact times and flow rates and the adsorption of major reaction components into
      the tubing wall. Using 0.5 mm ID tubing, lengths of 40 cm and residence times up
      to 45 min, none of the tested polymeric materials was found to affect subsequent
      PCR amplification. However, after exposure of the mixture to tubing lengths of 3
      m or reduction of sample volume, PCR inhibition occurred, increasing with the
      volume to length ratio. Different flow velocities did not affect PCR yield. When
      the adsorption of individual PCR components was studied, significant DNA
      adsorption and even more significant adsorption of the fluorescent dye Sybr Green
      I was found. The results indicate that PCR inhibition in polymeric tubing results
      from adsorption of reaction components to wall surfaces, increasing substantially
      with tubing length or sample volume reduction, but not with contact time or flow
      velocities typical in dynamic PCR amplification. The data also highlight that
      chemical compatibility of polymeric capillaries with DNA dyes should be carefully
      considered for the design of quantitative microfluidic devices.

PMID- 17180708
TI  - Molecular cloning and characterization of the DNA adenine methyltransferase gene
      in Feldmannia sp. virus.
AB  - The genome of Feldmannia sp. virus (FsV), a marine brown alga virus, contains a
      putative DNA adenine methyltransferase (dam) gene of 1,245 bp that encodes a
      polypeptide of 45.8 kDa. A BLAST search with the FsV dam gene showed high amino
      acid identity to two putative methyltransferase genes, ORF B29 of Feldmannia
      irregularis virus (FirrV, 54%) and ORF129 of Ectocarpus siliculosus virus (EsV,
      36%); and a PSI BLAST search revealed similarity to the N(6)-adenine
      methyltransferases (MTases) of other species. Most conserved motifs of beta-class
      MTases were observed in the FsV dam gene. However, neither of the highly
      conserved sequences in motifs I (FxGxG) or IV [(S/N/D)PP(Y/F/W)] perfectly
      matched those in the FsV dam gene. The highly conserved DPPY consensus sequence
      in motif IV was NTPW in the FsV dam gene, perfectly matching the sequences in ORF
      B29 of FirrV and ORF129 of EsV. Therefore, the dam genes in brown algae viruses
      may belong to a yet undiscovered group. The FsV Dam protein expressed from the
      cloned FsV dam gene methylated E. coli chromosomal DNA. This is the first report
      showing that a virus infecting marine filamentous brown algae encodes a
      functional Dam protein.

PMID- 17180710
TI  - Manufacturing monodisperse chitosan microparticles containing ampicillin using a
      microchannel chip.
AB  - The purpose of this study was using a developed microfluidic chip to prepare size
      controlled monodisperse chitosan microparticles encapsulating ampicillin. Our
      strategy is that a chitosan aqueous solution (the disperse phase) is fed into the
      microfluidic chip equipped with a cross-junction microchannel, and is sheared by
      the viscous oil flows (the continuous phase) to form monodisperse semi-product,
      chitosan emulsions. These fine emulsions are then gelled into stability upon
      gelation by injection of copper sulfate solution at the terminal microchannel of
      the microfluidic chip, and finally the uniform chitosan microparticles are formed
      in an efficient manner. The proposed chip is fabricated by a CO(2) laser machine
      on a conventional poly methyl methacrylate (PMMA) substrate. This microfluidic
      chip has four inlet ports, one cross-channel and one outlet port. We have
      demonstrated that one can control the size of chitosan microparticles from 100 to
      800 microm in diameter (with a variation less than 5%) by altering the relative
      sheath/sample flow rate ratio. Experimental data showed that when given a steady
      continuous phase (oil flow), the emulsion size increases with the increase in
      average velocity of the dispersed phase flow (sample flow). In addition, the
      release of the model drug (ampicillin) from these microspheres is proved to be
      once-daily for clinical application. We also revealed that appropriate particle
      sizes for different release patterns are predictable, enabling better
      applications of chitosan as a drug carrier.

PMID- 17180711
TI  - The RANK/RANKL/OPG triad in cancer-induced bone diseases.
AB  - The maintenance of skeletal integrity in a healthy individual requires a balanced
      regulation of the processes of bone formation, mediated by osteoblasts, and bone
      resorption, mediated by osteoclasts. This balanced process of bone remodeling
      becomes co-opted in the skeleton by tumor cells and this dramatically accelerates
      the process of remodeling and disrupts the normal equilibrium resulting in a
      spectrum of osteolytic to osteoblastic bone lesions. Certain tumor types, such as
      breast and prostate, frequently metastasize to the bone. It is now widely
      understood that the molecular triad--receptor activator of NF-kappaB ligand
      (RANKL), its receptor RANK, and the endogenous soluble RANKL inhibitor,
      osteoprotegerin (OPG)--play direct and essential roles in the formation,
      function, and survival of osteoclasts. Osteoclastic bone resorption contributes
      to the majority of skeletal sequelae, or skeletal-related events (SREs), in
      patients with bone metastases. In addition, osteoclastic bone resorption also
      contributes to the establishment of tumors in the skeleton. Therefore, blocking
      osteoclast activity and differentiation via RANKL inhibition may not only provide
      a beneficial treatment for skeletal complications of malignancy, but may also
      prevent bone metastases. In this review, we will first describe the operative
      role of osteoclasts and the RANK/RANKL/OPG triad in the pathophysiology of cancer
      induced bone diseases, specifically solid tumor metastases to the bone. Secondly,
      we will describe a therapeutic approach that specifically targets the RANKL
      molecule.

PMID- 17180712
TI  - Heritability of bipolar EEG spectra in a large sib-pair population.
AB  - The additive genetic heritability of both monopolar and bipolar EEG spectral
      power in a sample of 305 non-twin sibships comprising 690 individuals (age range
      7-65) was estimated in order to investigate their regional variation. The
      heritabilities of the bipolar EEG spectral power ranged from 0.10 to 0.63 in 38
      electrode-pairs, and those of monopolar power ranged from 0.23 to 0.68 in 19
      electrodes in six frequency bands from theta to high beta. The bipolar data shows
      significantly greater topographic variation compared to that of the monopolar
      data. The mean of bivariate genetic correlations were consistently lower for the
      bipolar data and the coefficients of variation consistently higher when compared
      to those of the monopolar data for each of the frequency bands. The results from
      the bipolar derivations are in greater accord with genetic findings in brain
      anatomy and show the possibility of multiple genetic sources for the phenotypic
      variability of EEG activity.

PMID- 17180714
TI  - Brief report: relative effectiveness of different home-based behavioral
      approaches to early teaching intervention.
AB  - The effectiveness of home-based early behavioral interventions for children (2:6
      4:0 years old) with autistic spectrum disorders was studied over 9-10 months.
      Measures of autistic severity, intellectual, educational, and adaptive behavioral
      functioning were taken. There was no evidence of recovery from autism. High
      intensity behavioral approaches (mean 30 h/week) produced greater gains than low
      intensity programs (mean 12 h/week). Lovaas- and complete application of behavior
      analysis to schools approach-type interventions produced largest gains [similar
      to gains produced by longer-term clinic-based applied behavior analysis (ABA)
      programs]. Within the high-intensity groups, increased temporal input on the
      program was not associated with increased gains in the children. The results from
      clinic-based ABA trials were partially replicated on a home-based sample, using
      children with greater autistic and intellectual impairments.

PMID- 17180715
TI  - Social approach and autistic behavior in children with fragile X syndrome.
AB  - Social avoidance is a core phenotypic characteristic of fragile X syndrome (FXS)
      that has critical cognitive and social consequences. However, no study has
      examined modulation of multiple social avoidant behaviors in children with FXS.
      In the current study, we introduce the Social Approach Scale (SAS), an
      observation scale that includes physical movement, facial expression, and eye
      contact approach behaviors collected across multiple time points. Our findings
      suggested that social approach behaviors in children with FXS were affected by
      age, gender, setting, and time spent with an examiner. Selected social approach
      behaviors were related to autistic behavior. Increased eye contact over the
      course of a research assessment, in particular, was found to be a strong
      predictor of lower autistic behavior.

PMID- 17180713
TI  - Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion).
AB  - The extent to which the phenotype of children comorbid for velocardiofacial
      syndrome (VCFS) and autism spectrum disorders (ASD) differs from that of VCFS
      only has not been studied. The sample consisted of 41 children (20 females) with
      VCFS, ranging in age from 6.5 years to 15.8 years. Eight children with VCFS met
      formal DSM-IV diagnostic criteria for autism based upon the ADI-R. These eight
      plus an additional nine participants met diagnostic criteria for an autistic
      spectrum disorder (VCFS + ASD). Ninety-four percent of the children with VCFS +
      ASD had a co-occurring psychiatric disorder while 60% of children with VCFS had a
      psychiatric disorder. Children with VCFS + ASD had larger right amygdala volumes.
      All other neuroanatomic regions of interest were statistically similar between
      the two groups.

PMID- 17180716
TI  - A parent-report instrument for identifying one-year-olds at risk for an eventual
      diagnosis of autism: the first year inventory.
AB  - A parent-report instrument, the First Year Inventory (FYI), was developed to
      assess behaviors in 12-month-old infants that suggest risk for an eventual
      diagnosis of autism. The target behaviors were identified from retrospective and
      prospective studies. FYIs were mailed to 5,941 families and 25% (N = 1,496) were
      returned, with higher return rates for white families and for families with
      greater educational attainment. Ad hoc groups of questions afforded measurement
      of eight specific constructs, which were combined to establish a general risk
      index. Boys had higher risk scores than did girls. Maternal race and education
      influenced answers. A small percentage of infants appeared to be at notably
      elevated risk. Large-scale longitudinal research is warranted to determine
      whether the FYI can predict an eventual diagnosis of autism.

PMID- 17180717
TI  - Predictors of language acquisition in preschool children with autism spectrum
      disorders.
AB  - In 118 children followed from age 2 to 5 (59 with autism, 24 with PDD-NOS and 35
      with non-spectrum developmental disabilities), age 2 and age 3 scores of non
      verbal ability, receptive communication, expressive communication and
      socialization were compared as predictors of receptive and expressive language at
      age 5. Non-verbal cognitive ability at age 2 was generally the strongest
      predictor of age 5 language, while at age 3 communication scores were a stronger
      predictor of age 5 language for children with autism. Early joint attention as
      well as vocal and motor imitation skills were more impaired in children who did
      not develop language by age 5 (but had relatively strong non-verbal cognitive
      skills) than in children who did develop language by 5.

PMID- 17180718
TI  - Goal achievement and the accountability of consumer-run organizations.
AB  - This study explores how consumer-run organizations (CROs) can maintain
      independence while meeting the accountability needs of funding agencies. The
      importance of both funding agency needs for accountability and CRO needs for
      independence are discussed. A goal-tracking process is proposed as a potential
      strategy for balancing the potentially conflicting needs of accountability and
      independence. To demonstrate the utility of the goal tracking approach, this
      study analyzes goal tracking documentation in 3 years of quarterly reports from
      21 CROs (also known as consumer drop-in centers and self-help agencies). Results
      detail the different goals of CROs. A 68% goal achievement rate suggests general
      organizational competence. Furthermore, CRO operations appear to be relatively
      cost-efficient, with an average of $11.51 spent per person per day. The analysis
      of quarterly reports leads to a discussion of several insights that may be useful
      to CROs, funding agencies, researchers, and mental health professionals.

PMID- 17180719
TI  - Performance-based funding of supported employment for persons with severe mental
      illness: vocational rehabilitation and employment staff perspectives.
AB  - Vocational rehabilitation (VR) supervisors and counselors (n = 35) as well as
      supported employment (SE) program managers and employment specialists (n = 26)
      were enrolled in a 12-month evaluation comparing two models of funding services
      for persons with severe mental illness: fee-for-service and results-based funding
      (RBF). Quantitative measures of job satisfaction and preference for funding
      method were obtained prospectively on a quarterly basis, and SE staff activity
      logs were collected monthly. Qualitative data were collected using a series of
      focus groups conducted at the conclusion of the study. Despite recording a
      substantial increase in semi-annualized VR billing charges when using RBF (45
      49%), SE staff expressed less satisfaction with RBF over time. Staff raised
      concerns about increased financial risks and pressures to achieve job placements
      under RBF. Vocational rehabilitation staff were consistently more satisfied with
      RBF, expressing particular satisfaction with perceived effectiveness and the
      payment authorization process. Both VR and SE staff expressed some reservations
      about RBF, primarily concerning possible pressures for adverse client selection.

PMID- 17180720
TI  - Effects of a tobacco ban on long-term psychiatric patients.
AB  - A total ban on all tobacco products was implemented in a diverse psychiatric
      institution. A post hoc evaluation examined the effect of the ban on long-term
      patients by comparing their characteristics the year before the ban to the year
      after. Several variables measuring physical health, psychiatric symptomatology,
      feelings of well-being, and interpersonal conflict were coded with very high
      reliability from health records. For the majority of patients who were in the
      maximum security forensic division, the tobacco ban was associated with almost no
      detectable ill effects with some clear benefits. Among the remainder of the long
      term patients, the ban might have been associated with a temporary increase in
      physical aggression towards staff members. It was concluded that successful
      implementation, and the avoidance of ill effects, depended entirely on the
      success staff members had in actually preventing patient access to tobacco.

PMID- 17180721
TI  - The South Oaks Gambling Screen-revised Adolescent (SOGS-RA) revisited: a cut
      point analysis.
AB  - The lack of a criterion validity gold standard defining adolescent pathological
      gambling represents a major limitation of the adolescent gambling literature. The
      present study employed Receiver Operating Characteristic curve analysis (ROC) to
      examine the performance of the South Oaks Gambling Screen-Revised Adolescent
      (SOGS-RA) recommended cut-point of 4 against two-proxy gold standards: self
      identified need for, or receipt of, help for gambling. Logistic regression
      analysis examined the correlates of self-identified need for help with gambling.
      The sample was comprised of 12990 adolescents from Atlantic Canada whose average
      age was 15 years and 50% of whom were male. The SOGS-RA performed as well or
      better with these proxy gold standards than with proxies used in previous
      studies. We concluded that the proxy gold standards based on self-identified need
      for or receipt of help represent a pragmatic solution to the lack of an
      adolescent-specific definition of problem or pathological gambling. Students in
      grade seven and SOGS-RA scores of 4 or greater were independent predictors of
      self-identifying a need for help.

PMID- 17180722
TI  - Fidelity of implementation in Project Towards No Drug Abuse (TND): a comparison
      of classroom teachers and program specialists.
AB  - This paper presents the results of an effectiveness trial of Project Towards No
      Drug Abuse [TND], in which we compared program delivery by regular classroom
      teachers and program specialists within the same high schools. Within 18 schools
      that were randomly assigned to the program or control conditions, health
      classrooms were assigned to program delivery by teachers or (outside)
      specialists. Classroom sessions were observed by pairs of observers to assess
      three domains of implementation fidelity: adherence, classroom process, and
      perceived student acceptance of the program. Pre- and immediate posttest survey
      data were collected from 2331 students. Of the four composite indexes of
      implementation fidelity that were examined, only one (quality of delivery) showed
      a difference between specialists and teachers, with marginally higher ratings of
      specialists (p < .10). Both teachers and program specialists achieved effects on
      three of the five immediate outcome measures, including program-specific
      knowledge, addiction concern, and social self-control. Students' posttest ratings
      of the program overall and the quality of program delivery failed to reveal
      differences between the teacher- and specialist-led classrooms. These results
      suggest that motivated, trained classroom teachers can implement evidence-based
      prevention programs with fidelity and achieve immediate effects.

PMID- 17180723
TI  - Chernobyl disaster sequelae in recent immigrants to the United States from the
      former Soviet Union (FSU).
AB  - Long-term mental health sequelae of the 1986 Chernobyl disaster have been
      documented for exposed populations who remained in the former Soviet Union (FSU)
      (Havenaar et al., 1997), and in a cohort migrated to Israel (Cwikel et al.,
      1997). This paper reports on Chernobyl disaster sequelae in emigres (n = 321) to
      the United States. Demographic characteristics, migration factors, and self
      reported physical health were considered. Both geographical proximity to the 1986
      disaster, and perception of radiation risk stood as long-term indicators of
      current psychological distress. Proximity was related to poor self-perceived
      physical health, as well as current symptoms of depression (p<.05), anxiety
      (p<.01), and Chernobyl-related trauma distress (p<.001) on standardized measures.
      Environmental contamination as a reason for migration was also associated with
      greater mental health symptomatology.

PMID- 17180724
TI  - The HIV transmission gradient: relationship patterns of protection.
AB  - We describe a gradient of potential HIV transmission from HIV-infected persons to
      their partners and thence to uninfected populations. The effect of this newly
      discovered transmission gradient is to limit the spread of HIV. We roughly
      estimate a 2% long-term transmission probability for sex and 14% for drug
      injection for two-step transmission. Then we test theories to account for this
      pattern on a network sample of 267 inner city drug users and nonusers. Although
      HIV positive persons engaged in a high level of risk with one another, they
      engaged in less risk with HIV negative partners, and these partners engaged in
      even lower levels of risk with other HIV negative persons. Analyses suggest that
      the primary motivation for sexual risk reduction is partner protection, while
      emotional closeness is the major barrier. Hypotheses accounting for risk in terms
      of self protection, social norms, gender power, and drug use were weakly
      supported or unsupported.

PMID- 17180726
TI  - The effect of film thickness on thermal aerosol generation.
AB  - PURPOSE: Rapid heating of thin films of pharmaceutical compounds can vaporize the
      molecules, which leads to formation of aerosol particles of optimal size for
      pulmonary drug delivery. The aim of this work was to assess the effect of coated
      film thickness on the purity of a thermally generated (condensation) drug
      aerosol. MATERIALS AND METHODS: Pharmaceuticals in their free base form were
      spray-coated onto stainless steel foils and subsequently heated and vaporized in
      airflow via a rapid resistive heating of the foil. Aerosol particles were
      collected on filters, extracted, and analyzed using reverse phase HPLC to assess
      the amount of degradation induced during the vaporization process. RESULTS:
      Condensation aerosols of five pharmaceuticals were formed from a wide range of
      film coating thicknesses. All five showed a roughly linear trend of increasing
      aerosol purity with decreasing film thickness, although with quite different
      slopes. These findings are consistent with a model based on general vaporization
      and degradation kinetics. Small non-uniformities in the film do not significantly
      alter aerosol purity. CONCLUSIONS: Rapid vaporization of pharmaceuticals coated
      as thin films on substrates is an efficient way of generating drug aerosols. By
      controlling the film thickness, the amount of aerosol decomposition can be
      minimized to produce high purity aerosols.

PMID- 17180725
TI  - Preparation and characterization of nickel nanoparticles for binding to his-tag
      proteins and antigens.
AB  - PURPOSE: The purpose of these studies was to prepare nanoparticles (NPs) with a
      small amount of surface-chelated nickel for obtaining enhanced binding of
      histidine-tagged (his-tag) proteins compared to non-histidine-tagged protein
      binding to charged nanoparticles. MATERIALS AND METHODS: NPs were prepared from
      oil-in-water microemulsion precursors using emulsifying wax, 3 mM Brij 78 and 0.1
      mM DOGS-NTA-Ni lipid (referred to as Ni-NPs). The amount of lipid entrapped in
      the NPs was quantitated by atomic emission spectroscopy (AES). The Ni-NPs were
      investigated for binding to two his-tag proteins, green fluorescent protein (GFP)
      and his-tag HIV-1 Gag p24. In vivo studies in mice were carried out to evaluate
      the immune responses obtained to his-tag Gag p24 bound to Ni-NPs. RESULTS: AES
      studies demonstrated that approximately 5% of the DOGS-NTA-Ni lipid used was
      entrapped in the NPs. The optimal binding ratio his-tag GFP and his-tag Gag p24
      to Ni-NPs was found to be 1:33.7 and 1:35.4 w/w, respectively. This interaction
      was stable at 37 degrees C in PBS, pH 7.4 over 4 h and the interaction of his-tag
      GFP with the Ni-NPs was enhanced compared to control NPs prepared with no Ni on
      the surface (NTA-NPs). The in vivo studies demonstrated enhanced serum IgG and
      IgG2a responses to his-tag Gag p24 bound to Ni-NPs compared to protein adjuvanted
      with Alum or adsorbed on the surface of control NTA-NPs. CONCLUSIONS: Ni-NPs can
      be used to bind strongly to his-tag proteins. This system was demonstrated to
      have potential applications in vaccine delivery for enhancing immune responses to
      protein-based vaccines.

PMID- 17180728
TI  - Assessment of the first and second generation antihistamines brain penetration
      and role of P-glycoprotein.
AB  - PURPOSE: The sedating effect of first generation H(1)-antihistamines has been
      associated with their ability to penetrate the blood-brain barrier (BBB) and lack
      of efflux by P-glycoprotein (Pgp). Second generation H(1)-antihistamines are
      relatively free of sedation and their limited brain penetration has been
      suggested to arise from Pgp-mediated efflux. The objective of this work was to
      evaluate the role of Pgp in brain penetration of first and second generation
      antihistamines. METHODS: Potential of antihistamines to be Pgp substrates was
      tested in vitro using Madin Darby canine kidney cells transfected with human Pgp.
      The role of Pgp in limiting brain penetration of antihistamines was tested by
      using the in situ brain perfusion technique. RESULTS: Majority of antihistamines
      were Pgp substrates in vitro. Following in situ brain perfusion, the first
      generation antihistamines substantially penetrated into rat brain independently
      from Pgp function. The second generation antihistamines terfenadine and
      loratadine, achieved substantial brain penetration, which was further enhanced by
      Pgp inhibition by cyclosporin A (CSA). In contrast, fexofenadine and cetirizine,
      penetrated brain poorly regardless of CSA administration. CONCLUSIONS:
      Antihistamines greatly differ in their ability to cross the BBB as well as in the
      role of Pgp in limiting their transport into the CNS in vivo.

PMID- 17180727
TI  - Gene therapy of the other genome: the challenges of treating mitochondrial DNA
      defects.
AB  - Human mitochondrial DNA is a 16.5 kb circular DNA molecule located inside the
      mitochondrial matrix. Although accounting for only about 1% of total cellular
      DNA, defects in mitochondrial DNA have been found to have major effects on human
      health. A single mtDNA mutation may cause a bewildering variety of clinical
      symptoms mainly involving the neuromuscular system at any age of onset. Despite
      significant advances in the understanding of mitochondrial DNA defects at a
      molecular level, the clinical diagnosis of mtDNA diseases remains a significant
      challenge and effective therapies for such diseases are as yet unavailable. In
      contrast to gene therapy for chromosomal DNA defects, mitochondrial gene therapy
      is a field that is still in its infancy and attempts towards gene therapy of the
      mitochondrial genome are rare. In this review we outline what we believe are the
      unique challenges associated with the correction of mtDNA mutations and summarize
      current approaches to gene therapy for the "other genome".

PMID- 17180730
TI  - Mechanistic investigation of drug release from asymmetric membrane tablets:
      effect of media gradients (osmotic pressure and concentration), and potential
      coating failures on in vitro release.
AB  - PURPOSE: An asymmetric membrane (AM) tablet was developed for a soluble model
      compound to study the in vitro drug release mechanisms in challenge conditions,
      including osmotic gradients, concentration gradients, and under potential coating
      failure modes. Porous, semipermable membrane integrity may be compromised by a
      high fat meal or by the presence of a defect in the coating that could cause a
      safety concern about dose-dumping. METHODS: The osmotic and diffusional release
      mechanisms of the AM tablet were independently shut down such that their
      individual contribution to the overall drug release was measured. Shut off of
      osmotic and diffusional release was accomplished by performing dissolution
      studies into receptor solutions with osmotic pressure above the internal core
      osmotic pressure and into receptor solutions saturated with drug, respectively.
      The effect of coating failure modes on in vitro drug release from the AM tablet
      was assessed through a simulated high-fat meal and by intentionally compromising
      the coating integrity. RESULTS: The predominant drug release mechanism for the AM
      tablet was osmotic and accounted for approximately 90-95% of the total release.
      Osmotic release was shutoff when the receptor media osmotic pressure exceeded 76
      atm. Diffusional release of the soluble drug amounted to 5-10% of the total
      release mechanism. The observed negative in vitro food effect was attributed to
      the increased osmotic pressure from the high fat meal when compared to the
      predicted release rates in sucrose media with the same osmotic pressure. This
      suppression in drug release rate due to a high fat meal is not anticipated to
      affect in vivo performance of the dosage form, as the rise in pressure is short
      lived. CONCLUSIONS: Drug release from the AM system studied was determined to be
      robust to varying and extreme challenge conditions. The conditions investigated
      included varying pH, agitation rate, media osmotic pressure, media saturated with
      drug to eliminate the concentration gradient, simulated high fat meal, and
      intentionally placed film coating defects. Osmotic and diffusional shut off
      experiments suggest that the mechanism governing drug release is a combination of
      osmotic and diffusional at approximately 90-95% and 5-10%, respectively. In
      addition, the coating failure mode studies revealed this formulation and design
      is not significantly affected by a high fat meal or by an intentionally placed
      defect in the film coating, and more specifically, did not result in a burst of
      drug release.

PMID- 17180729
TI  - In SCID mice with transplanted joint tissues from rheumatism patients, a model
      mice of human rheumatoid arthritis, anti-human fas antibody (R-125224)
      distributes specifically to human synovium.
AB  - PURPOSE: We investigated the tissue distribution of a humanized anti-human Fas
      monoclonal antibody, R-125224, in SCID mice transplanted with synovial tissues
      from patients with rheumatoid arthritis (SCID-HuRAg mice). The binding kinetics
      of R-125224 was also determined, using isolated human synovial cells. MATERIALS
      AND METHODS: Tissue distribution was assessed at 1, 24 and 168 h after
      intravenous administration of (125)I-R-125224 to SCID-HuRAg mice (0.4 mg/kg). The
      in vitro binding of (125)I-R-125224 to isolated human synovial cells was
      investigated. RESULTS: After intravenous administration of (125)I-R-125224 to
      SCID-HuRAg mice, the radioactivity distributed to various tissues at 1 h.
      Thereafter, the radioactivity in the tissues gradually decreased except for the
      transplanted synovial tissues, in which the radioactivity increased in a time
      dependent manner, and at 168 h, the tissue/plasma concentration ratio was about
      1. The in vitro binding affinity of (125)I-R-125224 to human synovial cells was
      high with a dissociation constant of 1.32 +/- 0.62 nM and the binding was
      inhibited by non-labeled R-125224 in a concentration-dependent manner.
      CONCLUSION: R-125224, a candidate compound for treating rheumatoid arthritis,
      specifically distributed to the pharmacological target site, human synovium
      transplanted in SCID mice, with high affinity.

PMID- 17180732
TI  - Protein and mRNA expression of tissue factor pathway inhibitor-1 (TFPI-1) in
      breast, pancreatic and colorectal cancer cells.
AB  - BACKGROUND: Patients with solo tumour malignancy are at higher risk of developing
      venous thromboembolism. When prophylactic anticoagulation (and in particular
      heparin) is used during cancer therapy however, patients appear to have a
      prolonged survival. Tumours express large quantities of procoagulant molecules,
      which predispose patients to these conditions. Tissue Factor (TF) is an important
      example, which may have a role in the biology of malignant disease. Intra-tumour
      vessel coagulation however is not a common phenomenon. Our hypothesis is that
      cancer cells produce anticoagulant molecules, which may prevent intra-tumour
      vessel auto-coagulation. Our results show that one such factor--Tissue Factor
      Pathway Inhibitor (TFPI-1) is expressed by a number of different cancer cells.
      METHODS: Seven human cancer cell lines were studied: three breast, two colorectal
      and two pancreatic. Cells were maintained in cell culture, and at 90% confluence
      protein and RNA were extracted. RNA integrity was confirmed using an RNA
      integrity gel and RNA purity determined by spectrophotometry. Reverse
      transcription polymerase chain reaction (RT-PCR) was used for TFPI-1 mRNA
      detection and immunoblotting used for TFPI-1 protein detection. RESULTS: Six cell
      lines (two breast, two colorectal, and two pancreatic) expressed the TFPI-1 gene.
      Gene function was confirmed by detection of TFPI-1 protein expression in these
      cell lines. CONCLUSION: TFPI-1 is expressed by breast cancer and other cancer
      cell lines maintained in cell culture. This has not been previously reported.
      Functional expression of TFPI-1 by cancer cells suggests that it has an important
      role in cancer biology. Further experiments are required to establish its
      function.

PMID- 17180731
TI  - Assessment of a new prototype hydrogel CO( 2 ) sensor; comparison with air
      tonometry.
AB  - OBJECTIVE: Gastrointestinal ischemia is always accompanied by an increased
      luminal CO(2). Currently, air tonometry is used to measure luminal CO(2). To
      improve the response time a new sensor was developed, enabling continuous CO(2)
      measurement. It consists of a pH-sensitive hydrogel which swells and shrinks in
      response to luminal CO(2), which is measured by the pressure sensor. We evaluated
      the potential clinical value of the sensor during an in vitro and in vivo study.
      METHODS: The response time to immediate, and stepwise change in pCO(2) was
      determined between 5 and 15 kPa, as well as temperature sensitivity between 25
      and 40 degrees C at two pCO(2) levels. Three sensors were compared to air
      tonometry (Tonocap) in healthy volunteers using a stepwise incremental exercise
      test, followed by a period of hyperventilation and an artificial CO(2)-peak.
      RESULTS: The in vitro response time to CO(2) increase and decrease was mean 5.9
      and 6.6 min. The bias, precision and reproducibility were +5%, 3% and 2%, resp.
      Increase of 1 degrees C at constant pCO(2) decreased sensor signal by 8%. In vivo
      tests: The relation with the Tonocap was poor during the exercise test. The
      response time of the sensor was 3 min during hyperventilation and the CO(2) peak.
      CONCLUSION: The hydrogel carbon dioxide sensor enabled fast and accurate pCO(2)
      measurement in a controlled environment but is very temperature dependent. The
      current prototype hydrogel sensor is still too unstable for clinical use, and
      should therefore be improved.

PMID- 17180734
TI  - A large-scale collection of phenotypic data describing an insertional mutant
      population to facilitate functional analysis of rice genes.
AB  - In order to facilitate the functional analysis of rice genes, we produced about
      50,000 insertion lines with the endogenous retrotransposon Tos17. Phenotypes of
      these lines in the M2 generation were observed in the field and characterized
      based on 53 phenotype descriptors. Nearly half of the lines showed more than one
      mutant phenotype. The most frequently observed phenotype was low fertility,
      followed by dwarfism. Phenotype data with photographs of each line are stored in
      the Tos17 mutant panel web-based database with a dataset of sequences flanking
      Tos17 insertion points in the rice genome (http://tos.nias.affrc.go.jp/). This
      combination of phenotypic and flanking sequence data will stimulate the
      functional analysis of rice genes.

PMID- 17180733
TI  - Identification of a key functional region in harpins from Xanthomonas that
      suppresses protein aggregation and mediates harpin expression in E. coli.
AB  - In the current study, we identified a key functional region in harpins from
      Xanthomonas that suppressed protein aggregation and mediated its expression in E.
      coli. Our data suggested that the presence of two common features in harpins [Wei
      et al. (1992) Science 257:85-88], namely, high glycine content and lack of
      cysteine residues, were not sufficient for Xanthomonas to elicit hypersensitive
      response (HR) activity or heat stability. Additionally, bioinformatic analyses
      revealed that the secondary structure of a conserved N-terminal region consisting
      of 12 highly hydrophilic amino acids (QGISEKQLDQLL) was alpha-helical. Following
      site-directed mutagenesis deletion of this region, the three mutated harpin
      proteins, in cultures induced at 37 degrees C, failed to elicit a HR in tobacco
      leaves. However, at 24 degrees C, two mutated harpins retained the ability to
      elicit HR, albeit with lower expression levels than that noted with the wild
      type. SDS-PAGE and Western blot data suggested the HpaG mutant protein was found
      almost entirely in the inclusion body. These data demonstrated that these
      conserved amino acid residues played a critical role in protein aggregation and
      inclusion body formation in harpins from Xanthomonas.

PMID- 17180735
TI  - Use of a PTGS-MAR expression system for efficient in planta production of
      bioactive Arabidopsis thaliana plant defensins.
AB  - Plant defensins, exhibiting various levels of inhibitory activity against fungal
      pathogens, are potent candidates for pharmaceutical or agricultural antimycotics.
      Study of the plant defensins from the model plant Arabidopsis thaliana requires
      the purification of these peptides. However, heterologous production of defensins
      for large-scale in vitro bioactivity assays is often experienced as a major
      problem. In this study we describe the transgenic expression of a previously
      identified seed-specific and a so far uncharacterized plant defensin gene in
      their host A. thaliana using a formerly developed plant expression system.
      Therefore, both genes were cloned in a matrix attachment region (MAR) based plant
      transformation vector and expressed in post-transcriptional gene silencing (PTGS)
      impaired A. thaliana plants. The peptides were purified to homogeneity and were
      correctly processed, as confirmed by mass spectrometry analysis. Finally, they
      were assessed for their in vitro antifungal activity and mode of antifungal
      action. Our results indicate that the PTGS-MAR expression system can be applied
      to obtain significant amounts of bioactive, rightly processed plant peptides from
      leaves of first generation transgenic plants.

PMID- 17180736
TI  - Urological management of indinavir-associated acute renal failure in HIV-positive
      patients.
AB  - INTRODUCTION: Indinavir, a protease inhibitor that is commonly used to treat HIV
      infection, may cause crystal formation within the renal tubules when urine pH is
      above 3.5. Crystallization in the urine may lead to intrarenal crystal deposition
      and acute renal failure (ARF). AIM: To establish the beneficial urological
      management of acute renal failure caused by indinavir treatment of HIV/AIDS
      patients. PATIENTS--METHODS: Five HIV positive patients (four men, one woman)
      with a mean age of 32 years (range 28-36 years) were referred to our Department
      of Urology from an AIDS outpatient Clinic, because of the development of
      postrenal acute renal failure with continuously elevated creatinine and urea
      plasma levels after indinavir therapy. Among the initial therapeutic maneuvers,
      indinavir administration was interrupted for 1 week while bilateral double-J
      ureteral stents were inserted in all the HIV/AIDS patients, during the first 24
      72 h to secure upper-tract drainage. Concurrently urine has been acidified by
      oral administration of the amino acid L: -methionine and oral fluid intake was
      increased. RESULTS: All the patients responded well to the treatment and their
      renal function was effortlessly restored to normal within a few days. CONCLUSION:
      HIV-positive patients receiving indinavir therapy might be complicated by acute
      renal failure, mainly due to intrarenal crystal deposition (tubules) or
      urolithiasis (postrenal obstruction). This adverse effect may simply manage by
      the discontinuation of indinavir administration, urine acidification, as well as
      the possible early insertion of bilateral double-J ureteral stents.

PMID- 17180737
TI  - A delayed case of renal artery pseudoaneurysm presented with gross hematuria and
      azotemia in solitary kidney following percutaneous nephrostomy: treated by
      transcatheter coil embolization.
AB  - Renal arteriovenous fistula or pseudoaneurysms developing after invasive
      procedures are either asymptomatic or show only transient symptoms. We describe
      here a case of symptomatic renal artery pseudoaneurysm that presented with gross
      hematuria and azotemia. The pseudoaneurysm of renal artery was diagnosed by
      ultrasonography and abdominal magnetic resonance imaging (MRI), and it was
      successfully treated by percutaneous transcatheter coil embolization. A high
      index of suspicion is essential for the early diagnosis and treatment of delayed
      gross hematuria in patients with history of percutaneous nephrostomy.

PMID- 17180738
TI  - Use of the University of California Los Angeles Integrated Staging System (UISS)
      to predict survival in localized renal cell carcinoma in an Asian population.
AB  - OBJECTIVES: To evaluate the applicability of the University of California Los
      Angeles Integrated Staging System (UISS) in predicting the prognosis of Chinese
      patients with localized renal cell carcinoma after radical nephrectomy, with
      reference to that reported by Patard et al in an international multicenter study
      (J Clin Oncol 2004, 22:3316-3322). METHODOLOGY: One hundred and twenty-eight
      Chinese patients with localized renal cell carcinoma were stratified into low
      risk (LR), intermediate risk (IR) and high risk (HR) groups according to the
      UISS, based on the TMN staging and Fuhrman grading of the tumor and the Eastern
      Cooperative Oncology Group performance status of the patients. The survival
      curves of each risk group were then calculated. RESULTS: The number of patients
      in the LR, IR and HR was 24 (18.8%), 94 (73.4%) and 10 (7.8%) respectively. The
      estimated 2-year survival rates were 100%, 89.9% and 100% for the LR, IR and HR
      groups respectively. Whereas the estimated 5-year survival rates were 93.3%,
      72.4% and 80% for the LR, IR and HR groups respectively. The LR and IR patients
      had comparable 2-year and 5-year estimated survival rates with those reported by
      Patard et al. However, the estimated survival rate for HR patients was better
      than that reported. CONCLUSIONS: UISS provided a valuable tool in predicting the
      survival of Chinese patients with localized renal cell carcinoma of LR and IR
      groups, as reported in other international centers. Further large scale study may
      be needed to confirm the applicability in HR population.

PMID- 17180739
TI  - A comparison of the vascular density of VEGF expression with microvascular
      density determined with CD34 and CD31 staining and conventional prognostic
      markers in renal cell carcinoma.
AB  - AIM: The aim of this study was to compare the vascular density of Vascular
      endothelial growth factor (VEGF) expression with microvascular density determined
      by CD34 and CD31 with conventional prognostic parameters. METHODS: The study
      involved 50 renal cell carcinoma (RCC) cases. VEGF, CD34, and CD31 were stained
      by immunohistochemistry, and then preparations were evaluated by two pathologists
      under light microscopy. The whole tumor area was scrutinized in all the sections.
      In the evaluation of VEGF, due to the lack of homogenous staining within the
      tumor, two parameters, distribution and intensity of expression, were evaluated
      semiquantitively. In the evaluation of microvascular density with CD34 and CD31
      staining, three hot areas with the highest density were determined. In x200
      magnification of these areas, on a single plane, the quantity of vascular
      structures with lumens was determined. RESULTS: Intensity of VEGF Expression was
      higher in papillary type carcinoma of kidney parenchyma (P = 0.014) and it was
      significantly correlated with tumor stage (P = 0.013), survival time (P = 0.01),
      and tumor size (P = 0.035). Distribution of VEGF expression was also higher in
      papillary RCC (P = 0.055) and it was significantly correlated with tumor stage (P
      = 0.043) and tumor size (P = 0.039). Vascular density determined with CD34
      staining was higher in conventional RCC (P < 0.05); in addition, it was
      significantly correlated with distribution and intensity of VEGF expression (P <
      0.05) and tumor stage (P < 0.05). Vascular density determined with CD31 staining
      was not significantly correlated with tumor type, tumor stage, nuclear grade, and
      survival time. CONCLUSIONS: Intensity and distribution of VEGF were higher in
      papillary RCC. Both parameters were significantly correlated with tumor size,
      stage, and vascular density determined with CD34 staining. Intensity of VEGF was
      also significantly correlated with capsule invasion. Vascular density determined
      with CD34 staining, however, was higher in conventional RCC, and it was
      correlated with tumor size and stage.

PMID- 17180740
TI  - Hand-assisted laparoscopic radical cystoprostatectomy and urethrectomy with ileal
      conduit construction.
AB  - INTRODUCTION: Hand-assisted laparoscopy was first performed in the 1990s by
      inserting the surgeon's finger or hand through a small tight wound. Although
      leakage of gas from the incision initially limited the usefulness of the
      technique, the hand-assisted procedures have advanced extensively since the
      introduction of the hand-assisted laparoscopy port. Laparoscopic procedure has
      only rarely been applied to radical cystoprostatectomy. Favorable reports for
      laparoscopic radical prostatectomy encouraged us to attempt a cystoprostatectomy
      under hand-assisted laparoscopy. PATIENT: The patient was a 70-year-old male with
      an invasive bladder tumor and no distant metastasis. Informed consent for
      undergoing hand-assisted laparoscopic radical cystoprostatectomy and ileal
      conduit construction was obtained. METHODS AND RESULTS: The bladder was dissected
      free and extracted whole through the incision for the hand port. The bilateral
      ureters and a loop of small intestine were withdrawn through the same incision.
      An ileal segment was isolated and small intestine continuity was recovered. Each
      ureter was anastomosed to one extreme of the ileal segment that was then
      reintroduced into the abdomen. The stoma was constructed through the right side
      port without additional incision. No intraoperative complications were observed.
      Recuperation was unusually quick and painless, and few postoperative analgesics
      were needed. CONCLUSIONS: Hand-assisted laparoscopic cystoprostatectomy and
      urinary diversion could provide the advantage of decreased postoperative
      morbidity without the long operation time and technical difficulty of a strictly
      laparoscopic procedure.

PMID- 17180742
TI  - Immunohistochemical localization of estrogen receptors ERalpha and ERbeta in the
      spiny mouse (Acomys cahirinus) ovary during postnatal development.
AB  - This study was designed to determine the expression pattern of estrogen receptor
      (ER) subtypes in the Acomys cahirinus ovarian cells during its postnatal
      development. Immunohistochemical studies revealed the presence of ERalpha and
      ERbeta in germinal epithelium cells and interstitial tissue. Both these ER
      subtypes were also seen in granulosa cells and oocytes of growing follicles,
      however, the level of ERbeta expression was higher in comparison with ERalpha. In
      contrast to ERbeta, ERalpha protein was also present in theca cells. The
      expression of ERs increased with animals' age, but it decreased during follicular
      maturation. Moreover, the immunolocalization of ER subtypes in luteal cells
      showed that not ERbeta, but ERalpha expression is up-regulated throughout corpus
      luteum development. These immunohistochemical studies demonstrate, for the first
      time, that ERalpha is also expressed in the mouse granulosa cells and it may be a
      mediator of estrogen action in granulosa cells proliferation and differentiation.

PMID- 17180743
TI  - Lectin and other histochemical studies of the articular cartilage and the chondro
      osseous junction of the normal human knee joint.
AB  - There are few studies on normal, adult diarthrodial joints which look in detail
      at the histochemical properties of the chondro-osseous junctional region. This
      study of the normal human knee joint was performed using lectin and other
      histochemical techniques. There were differences in the reactions of mineralised
      cartilage compared to those of hyaline cartilage with the former demonstrating
      more collagen and less glycosaminoglycans. Lectin histochemistry revealed more
      accessible terminal 2-deoxy,2-acetamido-alpha-D: -galactose and more N
      acetyllactosamine but less fucosyl and alpha-2,6-linked-sialyl termini in the
      mineralised cartilage. The hyaline cartilage chondrocytes stained for N-glycans
      but those of mineralised cartilage did not. The staining patterns of
      prolongations and islands of uncalcified cartilage running through the calcified
      layer to abut bone and marrow spaces were distinct, resembling the patterns of
      the hyaline cartilage but with some unique features. A possible relationship was
      revealed between the presence of the Maclura pomifera ligand
      (Galbeta1,3GalNAcalpha1-) and mineralisation. Subchondral bone had a markedly
      restricted glycoprofile.

PMID- 17180744
TI  - The Eurasian nose: aesthetic principles and techniques for augmentation of the
      asian nose with autogenous grafting.
AB  - Nasal augmentation is a highly popular technique used among Asian patients to
      change the characteristic flat Asian nose to a more prominent nose. The extent of
      augmentation is determined by the aesthetic desires of the patient, and the
      method of augmentation is provided by the surgeon, who takes into account the
      technical limitations of his or her preferred technique and the proposed surgical
      result. Although a silicone prosthesis is the most common implant used to improve
      the nasal appearance, the author prefers an autogenous approach with the
      olecranon bone used as a dorsal implant and conchal cartilages used to improve
      nasal tip projection because of the long-term stable results. A series of 31
      cases over 15 years is reviewed. The technique varies little from that described
      for saddle nose by Hodgkinson in 1992 [5]. The procedure is a variation of the
      ulnar donor site originally described by Antia et al. [1].

PMID- 17180745
TI  - Operative time is a poor surrogate for the learning curve in laparoscopic
      colorectal surgery.
AB  - BACKGROUND: Previous studies have relied on conversion rate and operative time
      for construction of learning curves in laparoscopic colorectal surgery. The
      authors hypothesized that conversion rate and operative time were less important
      than complication and readmission rates in defining good outcomes and hence the
      learning curve. METHODS: A database of 287 consecutive laparoscopic colorectal
      resections from a single tertiary referral center was analyzed. Outcome measures
      included operative time, conversion rate, major and minor complications, length
      of hospital stay, and the 15- and 30-day hospital readmission rate. Data were
      analyzed both by surgeons and by quartile case numbers. RESULTS: A total of 151
      right colectomies and 136 left colectomies were performed between 1995 and 2005.
      For both right and left colectomies, the conversion rate decreased in each of the
      first three quartiles, reaching a nadir of 0% for right colectomies and 3% for
      left colectomies in the third quartile. The conversion rates increased slightly
      in the fourth quartile. The operative time remained stable for three quartiles,
      then increased slightly in the fourth quartile. Two surgeons managed 199 of the
      287 cases. Analysis of the two high-volume surgeons demonstrated that for left
      sided resections, the surgeon with the shorter operative times had the higher
      major complication rate (13% vs 2%), overall complication rate (22% vs 2%), 30
      day readmission rate (13% vs 0%), and length of stay (3.8 vs 3.1 days) (p < 0.05
      for all comparisons). CONCLUSIONS: In this series, operative time failed to
      decrease with experience, and shorter operative times did not correlate with
      better clinical outcomes. The failure of operative time to decline with
      experience often reflects surgeons' willingness to attempt more difficult cases
      rather than an accurate representation of a "learning curve." Therefore,
      complication and readmission rates are more important than operative time and
      conversion rates for evaluating the learning curve and quality of laparoscopic
      colorectal surgery.

PMID- 17180746
TI  - Molecular evolution of peptide methionine sulfoxide reductases (MsrA and MsrB):
      on the early development of a mechanism that protects against oxidative damage.
AB  - Methionine sulfoxide reductases, enzymes that reverse the oxidation of methionine
      residues, have been described in a wide range of species. The reduction of the
      diastereoisomers of oxidized methionine is catalyzed by two different monomeric
      methionine sulfoxide reductases (MsrA and MsrB) and is best understood as an
      evolutionary response to high levels of oxygen either in the Earth's atmosphere
      or possibly in more localized environments. Phylogenetic analyses of these
      proteins suggest that their distribution is the outcome of a complex history
      including many paralogy and lateral gene transfer events.

PMID- 17180748
TI  - Coffee drinking may benefit women's cardiovascular health.

PMID- 17180747
TI  - Multiple-stress tolerance of ionizing radiation-resistant bacterial isolates
      obtained from various habitats: correlation between stresses.
AB  - Isolation of five ionizing radiation (IR)-resistant bacteria by screening of
      isolates from various habitats classified as common and stressed is reported. IR
      resistant isolates exhibited varying degrees of resistance to gamma-radiation and
      were classified as highly and moderately radiation resistant. Resistance to
      ultraviolet (UV) radiation correlated well with gamma-radiation resistance,
      whereas a comparable desiccation resistance for all the highly and moderately
      radiation-resistant isolates was observed. However, salt tolerance failed to
      correlate with IR resistance, indicating a divergent evolution of the salt
      tolerance and radiation resistance. Characterization of isolates by the amplified
      rDNA restriction analysis profiling attested to the clustering of these isolates
      with their stress phenotype. 16S rRNA gene-based analysis of the isolates showed
      that the bacteria with similar-resistance physiologies clustered together and
      belonged to related genera. Hydrogen peroxide resistance and mitomycin survival
      patterns of the isolates indicated the roles of oxidative-stress tolerance in
      desiccation survival and recombination repair in higher radiation resistance,
      respectively.

PMID- 17180749
TI  - Aerobic exercise equipment. Home is where the gym is.

PMID- 17180750
TI  - As winter approaches, do you have any tips to prevent the possibility of having
      carbon monoxide in my house?

PMID- 17180751
TI  - Winners and losers in Framework 6.

PMID- 17180752
TI  - Other ways in palliative care.

PMID- 17180753
TI  - [Liberalization of the law with regard to physicians under contract to public
      health insurance bodies. New potential for cooperation by physicians].

PMID- 17180754
TI  - [Radiation protection. Implications for clinical practice on the new regulations
      governing roentgen ray irradiation and radioprotection].
AB  - In 2001 or 2002, the legislator made substantial alterations to the
      "Rontgenverordnung" [regulations governing use of roentgen ray radiation] and
      "Strahlenschutzverordnung" [regulations governing radiation protection]. This was
      done to bring German law in line with EU Directives 96/29/Euratom (basic safety
      standards for the protection of the health of workers and the general public
      against the dangers arising from ionizing radiation) and 97/43/Euratom (health
      protection of individuals against the dangers of ionizing radiation in relation
      to medical exposure). Proper use of radiation in medicine requires that those
      involved in its application are aware of the biological effect of radiation. When
      staff and others are protected good organization and appropriate technology at
      the workplace can achieve a great deal. In the new directives, the radiation
      protection for the patient is quantified and the responsibility of the physician
      is clearly pointed out. The most important aim is uniform quality throughout
      Europe in radiological diagnosis and radiation protection.

PMID- 17180755
TI  - Nausea and Vomiting: An Interdisciplinary Approach. Proceedings of an
      International Workshop, Duesseldorf, Germany, 30 September-1 October 2005.

PMID- 17180756
TI  - [Mirror phenomena in patients with different autoimmune disorders].
AB  - The aim of the article was to study functional asymmetry between hemispheres and
      to find an ability to mirror phenomena in 25 patients with systemic lupus
      erythematosus (SLE) and 12 patients with multiple sclerosis. Patients with SLE
      had the following individual profiles of functional asymmetry: right, mainly
      right, mixed and mainly left. Nobody of them had either symmetric or left
      profiles. An ability to mirror phenomena (mirror drawing and mirror writing) has
      been found in 56% of SLE patients with different individual profiles of
      functional asymmetry. These patients significantly differed from the control
      group and patients with multiple sclerosis.

PMID- 17180758
TI  - Correction: Standard HR.1.25, Element of Performance 1, for laboratory.

PMID- 17180757
TI  - [7-year experience in usage of mirapex in patients with different forms of
      primary parkinsonism].
AB  - The results of mirapex (pramipexol) treatment of 402 patients with Parkinson's
      disease and juvenile parkinsonism during the period from 6 months to 7 years are
      summarized. Mirapex was used in monotherapy as well as in combination with
      levadopa and other antiparkinsonic drugs. The drug was well tolerated and
      effective in rest tremor, hypokinesia, muscle rigidity and depression, the more
      pronounced effect being seen at the early stage of the disease. The use of
      mirapex allows an effective control of motor fluctuations developing during long
      term continuous levodopa therapy. The results obtained characterize mirapex as a
      drug of choice in the treatment of juvenile parkinsonism. In case of a break in
      mirapex treatment, the recommencement of treatment usually is not accompanied by
      reduced sensitivity to drug effect.

PMID- 17180759
TI  - Revision: Standard HR.1, Element of Performance 7, for health care staffing
      services.

PMID- 17180760
TI  - Guideline watch. CDC recommends universal, routine adult HIV screening.

PMID- 17180761
TI  - Constancy and characteristics of the anterior cutaneous branch of the first
      intercostal nerve: correcting the descriptions in human anatomy texts.
AB  - Human anatomy texts state that the anterior cutaneous branch of the first
      intercostal nerve (Rca-Th1) does not exist or that, even if it does, it is poorly
      developed. However, an anterior cutaneous branch in the first intercostal space
      (Rca-1) was observed in 74.8% of cases examined (104/139 sides) and was not
      poorly developed at all. Some of the observed Rca-I were even larger than the
      anterior cutaneous branches in the second intercostal space (Rca-ll). The segment
      of origin of the Rca-I was analyzed in 37 sides and 66.2% (49/74 branches) were
      confirmed to be from Th1. As a result, in contrast with traditional beliefs, it
      was shown that Rca-Th1 exists. The Rca-I was classified into two types according
      to the course and distribution: (i) an anterior cutaneous branch that appeared at
      the anterior end of the first intercostal space (ICS), ran through the pectoralis
      major muscle and extended in the first ICS (Rca-1); and (ii) another branch that
      appeared at the same place but ran downward along the anterior surface of the
      second costal cartilage, deep to the pectoralis major muscle, to reach the
      inferior edge of the second costal cartilage or the second ICS, passed through
      the pectoralis major muscle and extended to the second rib or the second ICS
      (pseudo Rca-2). It was found that 77.8% (35/45 branches) of Rca-1 and 48.3%
      (14/29 branches) of pseudo Rca-2 were derived from Th1. Accordingly, the author
      suggests that the description in human anatomy texts should be revised to read,
      '... the Rca-Th1 exists quite constantly and some of appear at a position
      resembling Rca-Th2'.

PMID- 17180762
TI  - [The Tenovofir trial in Cameroun. Analysis of the controversial positions and
      proposal for an ethical alternative].

PMID- 17180763
TI  - [H5N1: vaccine solutions in men and animals].

PMID- 17180764
TI  - Contraindication for dronabinol.

PMID- 17180765
TI  - Presumption of innocence: FDA's authority to regulate the specifics of
      prescription drug labeling and the preemption debate.

PMID- 17180766
TI  - Unravelling the X in sex.
AB  - New cytological techniques combined with genome-wide expression studies and ChIP
      on-chip have revealed that random X-inactivation is not a simple one-step process
      that occurs uniformly across the entire chromosome, but a complex series of
      events with clear links to both the epigenetic silencing of autosomal genes and
      the imprinted X-inactivation that occurs in male meiosis. It appears to be less
      bizarre, as the French love to say, and as such an even better model of
      epigenetic gene silencing, than previously thought.

PMID- 17180767
TI  - The Food and Drug Administration's evolving regulation of press releases: limits
      and challenges.

PMID- 17180768
TI  - When you have a hammer everything looks like a nail: misapplication of the False
      Claims Act to off-label promotion.

PMID- 17180769
TI  - Is Noerr-Pennington immunity still a viable defense against antitrust claims
      arising from Hatch-Waxman litigation?

PMID- 17180770
TI  - FDA v. ephedra: is it time to lift the ban?

PMID- 17180771
TI  - What will it take to reap the clinical benefits of pharmacogenomics?

PMID- 17180772
TI  - Enhancing risk management at ORA.

PMID- 17180773
TI  - Science, ethics and economics in FDA decision-making: the legal framework.

PMID- 17180774
TI  - Protecting FDA's ability to protect public health.

PMID- 17180775
TI  - Ethics and FDA.

PMID- 17180776
TI  - Disaster preparedness manual. The Florida Dental Association's five step guide
      for disaster preparedness & recovery. Second edition.

PMID- 17180777
TI  - Florida Dental Association. Sourcebook 2006-2007.

PMID- 17180778
TI  - Florida Dental Association. Membership directories.

PMID- 17180779
TI  - [Renal cell carcinoma with vena cava involvement].

PMID- 17180780
TI  - Quality guidelines for endodontic treatment: consensus report of the European
      Society of Endodontology.
AB  - The assurance of the quality of a service rendered by a member of the dental
      profession is an essential feature of any system of peer review in dentistry.
      This document addresses two essential elements: (i) appropriateness of treatment
      modality and (ii) quality or level of treatment rendered. In revising these
      guidelines the European Society of Endodontology is responding to a public and
      professional need. In receiving care of a specialized nature such as endodontic
      treatment, patients need and deserve treatment that meets the standard of care
      generally given by competent practitioners. The European Society of Endodontology
      has the expertise and professional responsibility necessary to assist the dental
      profession by instituting guidelines on the standard of care in the special area
      of Endodontics. In accepting this responsibility the European Society of
      Endodontology formulated treatment guidelines that are intended to represent
      current good practice.

PMID- 17180781
TI  - Negotiating workers' comp managed care contracts.

PMID- 17180782
TI  - Sonographic diagnosis in infantile cholestasis.

PMID- 17180783
TI  - Allergens and allergic diseases in children.
AB  - The prevalence of allergic diseases is increasing gradually. Exposure to
      allergens is one of the trigger factors for symptoms in sensitized individuals.
      House dust mites and cockroach are the two most common indoor aeroallergens in
      Taiwan. There are wide differences in the numbers in different locations and in
      different seasons of these allergens. Sensitization to food allergens is
      prominent in young infants and can predict further aeroallergen sensitization.
      However, whether early exposure to allergens might develop or prevent allergic
      diseases in later childhood requires further research. Up to the present,
      allergen avoidance has demonstrated no prominent clinical efficacy in the
      improvement of allergic symptoms, although it is able to reduce allergen load in
      the environment. In a clinical regard, allergen avoidance should still be
      included as a part of treatment plans and be well explained to patients.

PMID- 17180784
TI  - Differential diagnosis of infantile choledochal cyst with or without biliary
      atresia.
AB  - BACKGROUND: The choledochal cyst, a cystic dilatation of the biliary tree, in
      infancy may be associated with biliary atresia (BACH) or without biliary atresia
      (CH). Infants in both groups usually have similar clinical symptoms at
      presentation but different management and prognosis. METHODS: We retrospectively
      identified 29 infants, aged younger than 1 year, who had surgically proven
      choledochal cysts from 1991 to 2004. They were diagnosed as CH in 18 patients and
      BACH in eleven. They had undergone preoperative abdominal ultrasonography (29
      patients) and intravenous radionuclide cholangiography (IVRC) (19 patients).
      RESULTS: The comparison of the clinical characteristics and laboratory
      examinations between the two groups showed that BACH patients had no sex
      predominance contrasting to female predominance in CH patients, more often
      presented with prolonged jaundice and clay-colored stool, and had higher
      bilirubin levels. In diagnosing BACH by ultrasonography, using the diameter of
      the extrahepatic cystic dilatation < or =1.5 cm but not atretic gallbladder
      further increased the sensitivity, specificity, positive and negative predictive
      rates (81.8%, 100%, 100%, 90% vs 54.5%, 88.8%, 75%, 76.2%, respectively),
      yielding an increased diagnostic accuracy (93.1% and 75.9%, respectively). In
      diagnosing BACH by IVRC, the sensitivity, specificity, positive and negative
      predictive value and diagnostic acCuracy were 100%, 70%, 75%, 100% and 84.2%,
      respectively. CONCLUSIONS: We concluded that there were clinical and laboratory
      discrepancies between the two groups, including female predominance, prolonged
      jaundice, clay-colored stool, bilirubin levels and size of cyst. In diagnosing
      BACH, the accuracy of abdominal ultrasonography will be increased if we use the
      diameter of the extrahepatic cystic dilatation < or = l.5 cm but not atretic
      gallbladder as one of the diagnostic cretia. Hepatobiliary scintigraphy had less
      diagnostic accuracy than ultrasonography but can be added to exclude the
      diagnosis of BACH.

PMID- 17180785
TI  - Small versus large volume dilute surfactant lavage for meconium aspiration
      syndrome.
AB  - BACKGROUND: Surfactant lavage has been used to treat neonatal meconium aspiration
      syndrome (MAS). OBJECTIVE: To assess the effects of lavage with a small volume of
      dilute surfactant in neonates with MAS, and compare the results with those of
      historical controls treated with larger volumes. METHODS: From August 2002 to
      June 2005, we treated 11 newborns with MAS using 20 ml of dilute surfactant at a
      phospholipid concentration of 10 mg/ml (SVL group). We compared the results with
      those of 9 infants previously treated with large-volume lavage (LVL group), using
      40 ml of dilute surfactant, 5 mg/ml. RESULTS: Both groups were similar at
      baseline except for a higher mean birth weight in the LVL group (3.29+/-0.36 vs
      2.92+/-0.4 kg, P = 0.04). The lavage procedure was longer in the LVL than the SVL
      group (48.89 +/-7.41 vs. 30.91+/-5.83 mins, P <0.001). Measures of oxygenation,
      including mean PaO2, oxygenation index, and arterial/alveolar 02 ratio, showed no
      significant difference between the two groups. Adverse events in the LVL group
      included transient hypoxemia in 3 infants and white- out on chest x-ray in 5
      cases. None of the patients in the SVL group had these findings. The peak mean
      airway pressure in.the LVL group was higher than that in the SVL group (16.0+/-2.
      65 vs 13.3+/-3.01 cmH2O, P = 0.046). CONCLUSIONS: SVL has the same benefits in
      neonatal MAS as LVL. However, SVL appears to be associated with fewer adverse
      events.

PMID- 17180786
TI  - Metabolic disorders in children and adolescents with type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) in children and adolescents is
      increasing in incidence worldwide. It is the leading type of newly diagnosed
      diabetes in Taiwan among school children. T2DM is associated with metabolic
      syndrome in adults, so we tried to find out if these metabolic disorders are
      present in children. METHODS: From 1989 to 2003, 22 children and adolescents were
      diagnosed with T2DM in our hospital. Their ages ranged from 8.8 to 17.0 (11.7+/
      2.3) years; 6 of them were boys. We compared their clinical characteristics with
      those of 42 healthy and 237 obese children and adolescents. Physical examination
      was performed and plasma glucose and serum cholesterol, triglycerides, uric acid,
      creatinine, HDL-cholesterol, and insulin levels were measured and LDL-cholesterol
      was calculated. Demographic and laboratory data were compared among the T2DM,
      obese and control groups. RESULTS: The female: male ratio among the patients was
      2.7: 1; 18% were overweight and 68% obese, and 64% had acanthosis nigricans.
      There were no significant differences between the T2DM and obese groups in terms
      of biochemistry profiles except for the higher plasma glucose in the T2DM group.
      Children with T2DM had higher levels of cholesterol and triglycerides but lower
      levels of HDL-cholesterol compared with healthy children. Among obese children
      without T2DM, the levels of glucose, triglycerides, uric acid, insulin, HOMA-IR
      were higher than in the healthy group, and HDL-cholesterol levels were lower.
      CONCLUSIONS: Children with T2DM or obesity should be evaluated for metabolic
      disorders.

PMID- 17180787
TI  - Acute pancreatitis in children: 10-year experience in a medical center.
AB  - BACKGROUND: Acute pancreatitis is uncommon in children compared with adults. The
      purpose of this study was to evaluate the etiologies, clinical presentations,
      image findings and outcome of children's acute pancreatitis. METHODS: The medical
      records of children and adolescent patients admitted due to pancreatitis from
      July 1992 to July 2002 were reviewed. The diagnosis of pancreatitis was based on
      clinical symptoms, at least threefold elevation of serum pancreatic enzymes, and
      image findings. RESULTS: This study comprised 75 patients with 96 episodes of
      pancreatitis. There were 36 males and 39 females, with a mean age of 10 years.
      The leading etiologies were idiopathic (26.7%), systemic diseases (22.7%),
      biliary tract disease (21.3%), and trauma (16%). Common initial manifestations
      included abdominal pain (93.8%), vomiting (64.2%), and fever (33.3%). The
      sensitivities of ultrasonography (US) and computed tomography (CT) in detecting
      pancreatitis were 57.3% and 74.4%, respectively. The morbidity included 6
      pseudocysts and 16 repeated pancreatitis. Four pseudocysts were resulted from
      traumatic pancreatitis. Patients with hyperlipidemia and biliary tract disorder
      were more likely to have repeated attacks. Fifty-five (73.3%) patients recovered
      after conservative management, the remaining 20 (26.7%) patients needed surgical
      or other interventional treatment. The mortality rate was 5.3%. Three fatal cases
      (75%) had underlying medical diseases. CONCLUSIONS: The etiologies of acute
      pancreatitis are diverse. Abdominal CT is more sensitive than US in the diagnosis
      of pancreatitis. Pseudocysts are more likely to occur in patients with traumatic
      pancreatitis. Patients with hyperlipidemia are prone to recurrent pancreatitis.
      The prognosis of children's pancreatitis is good. Most patients with fatal
      outcome had coexistent medical diseases.

PMID- 17180788
TI  - Combined transcatheter closure of atrial septal defect and patent ductus
      arteriosus: report of two cases.
AB  - Atrial septal defect (ASD) and patent ductus arteriosus (PDA) are common
      congenital heart defects and usually isolate. The combination of these two
      defects is infrequent. Nowadays, both defects are amenable to transcatheter
      closure, without surgery. However, both defects by transcather closure was rarely
      reported. Here we report that two children with ASD and PDA benefited from
      combined interventional therapy using the Amplatzer septal occluder for the ASD
      and Gianturco coils for the PDA. Based on our limited experience, closing the PDA
      before the ASD may be a better option.

PMID- 17180789
TI  - Arteriovenous malformation of the mandible presented as massive upper
      gastrointestinal bleeding: report of one case.
AB  - Arteriovenous malformation is an uncommon cause of upper gastrointestinal
      bleeding in children. It should be taken into consideration when a child has
      upper gastrointestinal bleeding because without proper management, it might be
      fatal. We report a 10-year-old boy whose initial presentation was massive
      hematemesis and impending shock. After angiography, arteriovenous malformation
      (AVM) of the mandible was found and treated with embolization. This 10-year-old
      boy also had chicken pox during admission. Case reports regarding AVM of dental
      arches in literature are reviewed and the proposed managements are summarized.
      Embolization combined with surgical excision might be the optimal way to manage
      AVM of dental arches.

PMID- 17180790
TI  - Neonatal bacterial meningitis complicated with multiple brain abscesses and
      intraventricular rupture: report of one case.
AB  - Brain abscess is rarely encountered in neonates and carries a high morbidity and
      mortality. Here we report a premature infant who developed systemic Escherichia
      coli (E. coli) infection resulting in multiple brain abscesses with
      intraventricular rupture at 3 months postnatal age. He was treated successfully
      with a combination of surgical and antimicrobial therapies. Related literature on
      brain abscess with special emphasis on intraventricular rupture is reviewed.

PMID- 17180791
TI  - [Analyses of answers presented by children with and without specific language
      impairment].
AB  - BACKGROUND: children start to differentiate questions from non-questions and also
      start to adjust their answers at the age of two. This participation in verbal
      exchanges requires basic conversational abilities such as the competence to
      initiate interact and reply appropriately, and to maintain the interaction. AIM:
      to analyze and correlate the pragmatic aspects of language, related to the type
      of answers, during an adult/child interaction in children with normal language
      development and in those diagnosed with Specific Language Impairment (SLI).
      METHOD: 16 children with SLI (GP) and ages between three and six years, and 60
      children with normal language development (GC) and ages between three to five
      years - 20 for each age group, 10 of each gender. Data gathering occurred in two
      different days, with the adult/child interaction being facilitated by toys. Data
      (speech of child and adult) were transcribed and analyzed, obtaining a
      Reliability Index of 93.75%, and later were submitted to statistical analyses.
      RESULTS: answers were classified in categories and grouped according to the
      following: Adequate Answers (RA) and Inadequate Answers (RI), always in
      accordance to the established communicative context. GC presented a significantly
      higher average of RA when compared to GP, and GP presented a significantly higher
      average of RI when compared to GC. GC presented a decrease in the use of RI at
      the increase of age. GP maintained the use of RI at the increase of age,
      including the age group of six. CONCLUSION: it was observed that the increase in
      age emphasized differences between GP and GC. GP presented a less effective
      communication maintaining unintelligible speech, whereas GC presented more
      elaborate communication abilities. More studies with older children are necessary
      for the better understanding of the observed trends.

PMID- 17180792
TI  - [Analyses of the communicative functions expressed by language therapists and
      patients of the autistic spectrum].
AB  - BACKGROUND: communicative functions used by language therapists and patients.
      AIM: to analyze the communicative functions used by language therapists and
      patients of the autistic spectrum. METHOD: the communicative functions expressed
      by six therapists in interaction with six patients each were analyzed,
      constituting 36 profiles of communicative functions expressed by the dyad
      therapist-patient. All therapists were part of a Training Program in Childhood
      Psychiatric Disorders and the patients were diagnosed within the autistic
      spectrum. Data were gathered using the transcriptions of a videotaped therapy
      session and these were analyzed according to the criteria suggested by Fernandes
      (2000). The communicative functions were divided in two different ways:
      interpersonal and non-interpersonal, and instrumental, regulatory, interactive,
      personal, heuristic and imaginative. RESULTS: the comparison between the
      functions used by the language therapists and the patients indicated a
      statistically significant difference in use of the following functions: request
      of social routine, request of information, request of action, comment,
      recognition of other, exclamation, non-focused, exploratory, exhibition, play and
      reactive. There was also a statistically significant difference between the use
      of interpersonal, non-interpersonal, regulatory, interactive, personal and
      heuristic communicative functions. CONCLUSION: the functional communicative
      profile of language therapists is different from the one presented by their
      patients when comparing each communicative function and when the communicative
      functions are grouped (interpersonal and non-interpersonal, and instrumental,
      regulatory, interactive, personal, heuristic and imaginative). Therapists use
      communicative functions to fill in the communicative space and to make requests.
      This finding agrees with the findings of previous studies.

PMID- 17180793
TI  - [Anthropometrical measurements of the height of the upper lip and length of the
      philtrum].
AB  - BACKGROUND: indirect anthropometrical measurements of the height of the upper lip
      and length of the philtrum. AIM: to describe the measurements of the height of
      the upper lip and length of the philtrum, extracted from video x-rays, in
      children with mixed dentition, relating these measurements to facial typology-
      medium and long-, to occlusion--Angle's class I and II--and to the rest position
      of the lips--with and without lip seal. METHOD: verification of 123 x-rays, in
      lateral norm, of children with ages between 7:7 and 11:10 years, 56 male and 67
      female, extracted from archives of orthodontical documentation prior to
      treatment. RESULTS: the T-Student test, with a significance level of 5%, was used
      for the statistical analyses and the obtained results were: for the height of the
      upper lip no statistical difference was found considering the variables of face
      typology, occlusion and gender; there was no statistical difference for the
      measurements of the philtrum considering the variables of face typology and
      occlusion, but a statistically significant difference was found for the variable
      gender: a statistically significant difference was found for the height of the
      upper lip and length of the philtrum considering the variable rest position of
      the lips--with and without lip seal--being this a determinant factor for the
      measurements. This finding suggests that a direction of structural modifications
      may exist. CONCLUSION: the mean value for the height of the upper lip was
      established at 21mm; the mean value for the length of the philtrum was
      established at 12mm. It is important to consider the rest posture of the lips,
      during assessment and therapy, when taking the measurements of the height of the
      upper lip and length of the philtrum.

PMID- 17180794
TI  - [Acclimatization: speech recognition in hearing aid users].
AB  - BACKGROUND: acclimatization is the period that succeeds the fitting of hearing
      aids, when a progressive improvement of the hearing and speech recognition
      abilities is observed due to the new speech cues that are available to the
      hearing aid user. AIM: to verify acclimatization after the fitting of hearing
      aids through objective (speech tests) and subjective (Questionnaire) evaluations.
      METHOD: 16 hearing impaired individuals were evaluated on the first day of
      hearing aid fitting and were monthly reassessed for three months. In all three
      months the following speech tests were used: PISR - percentage index of speech
      recognition through monosyllabic words and SRT--speech recognition threshold
      through sentences, determining the speech/ noise ratio (S/N). The International
      Outcome Inventory of Hearing Aid (IOI-HA) was also applied in the first and third
      months after the hearing aids were fitted. RESULTS: the comparison between the
      first day, first, second and third months after the hearing aids were fitted
      revealed a statistically significant improvement (p<0.001) between the results,
      not only for the PISR but also for the S/N ratio. No statistically significant
      difference was found for the results obtained through the questionnaire applied
      in the first and third months. CONCLUSION: the objective evaluation, using speech
      recognition tests, presents better results in the months following the hearing
      aids fitting indicating a progressive improvement in the speech abilities from
      the first month onwards. The subjective evaluation does not reveal an improvement
      when comparing the first and third moths after the hearing aids were fitted.

PMID- 17180795
TI  - [Relationship between speech, tonus and non-verbal praxis of the stomatognathic
      system in preschoolers].
AB  - BACKGROUND: relationship between speech, tonus and non-verbal praxis. AIM: to
      verify the relationship between speech, tonus and non-verbal praxis of the
      stomatognathic system in preschoolers. METHOD: 120 children, with ages between
      4:0 and 5:11 years, were assessed. This assessment consisted of an anamnesis and
      a speech-language evaluation. The anamnesis was carried out with each child and
      was completed with information obtained through a questionnaire filled out by
      parents or guardians. The speech-language assessment involved: assessment of
      tonus (resistance), of mobility (execution of isolated movements), praxis of lips
      and tongue (repetition of sequential movements) and of speech (picture naming).
      RESULTS: statistically significant findings were: normal tongue tonus in the
      group of children with normal praxis (p = 0.003); tongue with altered tonus in
      the group of children with altered praxis (p = 0.003) and normal speech in the
      group of children with normal praxis (p < 0.001). Other observations were: normal
      lip tonus in the group of children with normal praxis (p = 0.058); altered speech
      (omission, substitution and distortion) in the group of children with altered lip
      tonus (p = 0.149), normal speech in the group of children with normal tongue
      tonus (p = 0.332): altered speech (omission, substitution and distortion) in the
      group of children with altered lip praxis (p = 0.241). Differences in speech
      related to gender or age were not observed in the present study. However,
      children with ages between 4:0 and 4:11 years presented speech alterations in a
      higher proportion when compared to children with ages between 5:0 and 5:11 years.
      CONCLUSION: it was not possible to prove the existence of a relationship between
      tonus and lip praxis, and between lip praxis and speech. A relationship exists
      between tonus and non-verbal tongue praxis and also between non-verbal tongue
      praxis and speech.

PMID- 17180796
TI  - [Auditory evoked potentials in individuals over 50 years].
AB  - BACKGROUND: auditory evoked potentials. AIM: to describe the results of brainstem
      auditory evoked potentials (PEATE), middle latency auditory evoked potentials
      (PEAML) and cognitive potential (P300) in individuals over 50 years. METHOD: this
      study was developed at the Speech and Hearing Investigation Laboratory in
      Auditory Evoked Potentials of the Speech-Language and Hearing Course of the
      Department of Physiotherapy, Speech-language and Hearing Sciences and
      Occupational Therapy of FMUSP. Twenty four subjects (45 ears) were evaluated
      through PEATE and P300, and only 18 of these subjects (36 ears) were evaluated
      through PEAML. All subjects had ages between 51 and 74 years and were divided in
      three groups: GI (50-59 years), GII (60-69 years) and GIII (70-79 years). All
      subjects presented either normal hearing or neurossensorial hearing loss of a
      moderate-severe level in the PEATE, and of a moderate level in the PEAML and in
      the P300. The frequency range evaluated in the PEATE and in the PEAML varied from
      3000 to 6000Hz, while in the P300 it varied from 1000 to 1500Hz. For the
      statistical analyses of the data, the Kruskal-Wallis test, the Mann-Whitney test
      and the two proportion equality test were used. RESULTS: significant statistical
      differences were simultaneously observed between the groups for the interpeak I-V
      in the PEATE and for the Na wave latency in the PEAML - in the PEATE the
      difference was caused by GIII and in the PEAML it was caused by GI. A
      statistically significant difference between the groups was observed for the
      latency of the P300 component. Considerable alterations were also found regarding
      the quality of the responses of the auditory evoked potentials, indicating a
      strong correlation between the deterioration of the responses and the increase in
      age. CONCLUSION: the aging process of the auditory system progressively affects
      the auditory pathways throughout the brainstem and temporal lobe.

PMID- 17180797
TI  - [Ordering and temporal resolution in professional singers and in well tuned and
      out of tune amateur singers].
AB  - BACKGROUND: temporal ordering and temporal resolution. AIM: to compare the
      performance of professional singers with that of well tuned and out of tune
      amateur singers in the pitch pattern test (PPT) and in the Random Gap Detection
      Test (RGDT). METHOD: participants were 78 individuals, male and female, with ages
      ranging from 18 to 55 years. All of the participants were singers with normal
      hearing - previously assessed using pure tone and speech audiometry--and had no
      language, speech, voice or hearing complaints. Each individual answered a
      questionnaire concerning, among other subjects, perception about own voice when
      singing, number of years of professional singing, difficulties when singing new
      songs and number of years of music study. For the objective assessment the PPT
      and the RGDT were used in order to investigate temporal ordering and temporal
      resolution respectively. RESULTS: regarding the RGDT, there was no statistically
      significant difference between the groups and variables. As for the PPT, it was
      observed that professional singers presented a better performance, with statistic
      significance, when compared to well tuned amateur singers and these a better
      performance when compared to out of tune amateur singers. The performance in the
      PPT was related to specialized training and study of music theory. CONCLUSION:
      the RGDT did not prove to be a sensitive test to distinguish professional and
      amateur singers. On the other hand, the PPT did. The performance in the PPT
      reflects the number of years of specialized auditory training and music theory
      study.

PMID- 17180798
TI  - [Auditory training in workshops: group therapy option].
AB  - BACKGROUND: auditory training in groups. AIM: to verify in a group of individuals
      with mental retardation the efficacy of auditory training in a workshop
      environment. METHOD a longitudinal prospective study with 13 mentally retarded
      individuals from the Associacao de Pais e Amigos do Excepcional (APAE) of
      Congonhas divided in two groups: case (n=5) and control (n=8) and who were
      submitted to ten auditory training sessions after verifying the integrity of the
      peripheral auditory system through evoked otoacoustic emissions. Participants
      were evaluated using a specific protocol concerning the auditory abilities (sound
      localization, auditory identification, memory, sequencing, auditory
      discrimination and auditory comprehension) at the beginning and at the end of the
      project. Data (entering, processing and analyses) were analyzed by the Epi Info
      6.04 software. RESULTS: the groups did not differ regarding aspects of age (mean
      = 23.6 years) and gender (40% male). In the first evaluation both groups
      presented similar performances. In the final evaluation an improvement in the
      auditory abilities was observed for the individuals in the case group. When
      comparing the mean number of correct answers obtained by both groups in the first
      and final evaluations, a statistically significant result was obtained for sound
      localization (p=0.02), auditory sequencing (p=0.006) and auditory discrimination
      (p=0.03). CONCLUSION: group auditory training demonstrated to be effective in
      individuals with mental retardation, observing an improvement in the auditory
      abilities. More studies, with a larger number of participants, are necessary in
      order to confirm the findings of the present research. These results will help
      public health professionals to reanalyze the theory models used for therapy, so
      that they can use specific methods according to individual needs, such as
      auditory training workshops.

PMID- 17180799
TI  - [Picture naming and imitation tests as tools for the diagnosis of phonological
      disorder].
AB  - BACKGROUND: phonological disorder. AIM: to verify the association between the
      phonological performance in picture naming and imitation tasks, assessing the
      occurrence of phonological processes and using the severity indexes of Percentage
      of Correct Consonants and Phonological Density Index. METHOD: participants of
      this research were 50 phonologically disordered children, with no history of
      prior speech-language therapy and with ages between 4:0 and 12 years. RESULTS:
      The analysis of the phonological processes indicated that the non-productive
      processes were more frequent than the productive ones, not only in the imitation
      task but also in the picture naming task. It was observed that in both tasks,
      most participants presented the phonological processes of cluster reduction,
      liquid simplification and final consonant deletion, independently of their
      productivity. When comparing both tasks, there was an association and agreement
      regarding the number of participants who presented phonological processes as well
      as a correlation regarding the total number of phonological processes; there was
      no evidence of differences concerning the averages of the phonological processes
      observed in the imitation and picture naming tasks; a negative correlation was
      observed between the severity indexes Percentage of Correct Consonants and
      Phonological Density Index; moreover, these values presented a strong correlation
      in both tests, indicating that they detect similar severity levels. CONCLUSION:
      the study verified an association and agreement between the picture naming and
      imitation tasks, not only for the number of participants who presented
      phonological processes, but also for the number of phonological processes, thus
      indicating the importance of using structured tests for the diagnosis of
      phonological disorder. Furthermore, for the severity indexes, Percentage of
      Correct Consonants and Phonological Density Index, a high correlation was
      observed between the tasks, indicating that both tasks are useful instruments in
      detecting phonological disorder.

PMID- 17180800
TI  - [Respiratory dynamics measurements in children with four to ten years of age].
AB  - BACKGROUND: respiratory dynamics measurements are frequently used in the speech
      language pathology practice, but few are the scientific data for children. AIM:
      to study the respiratory dynamics in children with nasal breathing. METHOD: the
      study was performed with a stratified random sample of 106 nasal breathing
      children, male and female, from schools of the city of Marilia-SP, with ages
      between four and ten years. The following measurements were obtained: vital
      capacity (VC) in both standing and sitting positions, with and without nasal
      occlusion; maximum phonation time (MPT) of sustained vowels and consonants and
      also of speech when counting numbers. RESULTS: the mean values for VC in the
      standing position with and without nasal occlusion were of 1515.56ml and
      1538.67ml respectively and for the sitting position of 1524ml and 1539.15ml
      respectively. MPT of vowels in seconds were: /a/ = 8.32, /i/ = 8.61 and /ul =
      8.42; of consonants: /s/ = 6.64 and /z/ = 7.65; and when counting numbers: 7.76.
      It was observed that the mean values of these measurements progressively
      increased according to age. There was a statistically significant difference
      (p<0.05) not only for the MPT of vowels but also for the MPT of consonants in
      older children, i.e. between 4 and 10 year olds, 4 and 9 year olds and 4 and 8
      year olds. There was no significant statistical difference for the VC values in
      consecutive age groups. There was a strong association between VC and the child's
      physical development. CONCLUSION: this study presented respiratory dynamics
      measurements in children that can be used for the spech-language diagnosis and
      therapy. Other studies should be developed in order to bring additional
      information on the subject.

PMID- 17180801
TI  - [Bone conduction auditory brainstem responses in normal hearing individuals].
AB  - BACKGROUND: bone conduction auditory brainstem responses (ABR) in normal hearing
      individuals. AIM: to evaluate the clinical applicability of bone conduction ABR,
      characterizing normality and determining an assessment protocol. METHOD:
      participants of this study were 22 individuals with normal hearing (20dB NA),
      with ages between 20 and 30 years, 14 female and 8 male. All individuals were
      assessed using air and bone (vibrator positioned on the forehead and mastoid)
      conduction ABR. EP25 equipment, Interacoustic; 3A insertion phone; B-71 bone
      vibrator; click stimulus. RESULTS: it was possible to evaluate the bone
      conduction ABR in all individuals. The results demonstrate that the
      electrophysiological threshold obtained when the vibrator was positioned on the
      forehead (32.69+/-5.63 and 32.5+/-7.07dB nHL) was higher than that obtained when
      the vibrator was positioned on the mastoid (25.00+/-7.33 and 30.00+/-5.34dB nHL)
      for both genders respectively. For this reason the vibrator was positioned on the
      mastoid. The electrophysiological threshold obtained by bone conduction was
      higher than that obtained by air conduction for both genders and also when all
      individuals were grouped together. Thus it is necessary to use a correction
      factor, according to the results, of 10dB nHL. The latency-intensity values of
      the V wave in the ipsilateral and contralateral recordings differed statistically
      according to gender, and should be considered separately. The value of 26.81+/
      6.99dB nHL was adopted as being the normal threshold for bone conduction ABR.
      CONCLUSION: it is possible to evaluate bone conduction ABR in the clinical
      environment. These results, when considered along with the air conduction ABR,
      increase the chances of a more precise diagnosis regarding the type of hearing
      loss.

PMID- 17180802
TI  - [Genetics and language in Williams-Beuren Syndrome: a distinct neurobehavioral
      disorder].
AB  - BACKGROUND: genetic, cognitive and language aspects of the Williams-Beuren
      Syndorme (WBS). AIM: to present a review of the literature about WBS,
      highlighting its genetic, cognitive and language characteristics. CONCLUSION: the
      literature indicates that although the etiology of WBS is known, early diagnosis
      is difficult due to the great variability of its clinical characteristics. This
      great phenotypic variability has been associated to a deletion of several genes
      in region 7q 11.23 which includes the elastin gene. The deletion of this gene is
      identified by the Fluorecent in situ Hibridization test (FISH). The incidence of
      this syndrome is 1 in every 20,000 birth and is the result of a "de novo" genetic
      alteration. The syndrome is characterized by an elfin type face, cardiac
      alterations, cognitive deficits and behavioral aspects that include language. A
      peculiar cognitive profile has often been described as consisting of outstanding
      social and verbal skills associated to visuo-spatial impairments. Cognitive
      deficits are variable and may not be present. Studies that describe language
      abilities indicate that syntax might be intact or partially intact; speech can be
      precise and intelligible indicating that the phonological system is preserved.
      The receptive vocabulary is mentioned in a few studies as being adequate and in
      others as being impaired according to mental age. Researches have produced
      incongruent findings regarding the cognitive and linguistic abilities. The
      correlation between the language and cognitive abilities and the divergent
      findings presented in the literature will be discussed in this article.

PMID- 17180804
TI  - [Surveillance on Pseudomonas aeruginosa isolated in Gifu prefecture (2004)].
AB  - We analyzed Pseudomonas aeruginosa isolates in Gifu prefecture between September
      and October 2004. We conducted antimicrobial susceptibility test for 266 strains
      isolated from 8 medical institutes and 1 clinical laboratory, based on broth
      microdilution method. The MIC50 and MIC90 of piperacillin, amikacin, imipenem,
      and ciprofloxacin were 4 and 64, 4 and 8, 1 and 16, 0.25 and 8 microg/mL,
      respectively. The strains isolated from urine had higher MIC level in comparison
      with from sputum, which was remarkable in penicillins, cephalosporins and
      fluoroquinolones. We isolated 7 strains of multi-drug resistant Pseudomonas
      aeruginosa (MDRP), in which 3 strains showed under 16 microg/mL in MIC against
      anti-MRSA (methicillin-resistant Staphylococcus aureus) drug arbekacin.
      Continuous surveillance would be needed for antimicrobial resistance on P.
      aeruginosa in Gifu prefecture.

PMID- 17180803
TI  - [Susceptibilities of bacteria isolated from patients with lower respiratory
      infectious diseases to antibiotics (2004)].
AB  - From October 2004 to September 2005, we collected the specimen from 319 patients
      with lower respiratory tract infections in 12 institutions in Japan, and
      investigated the susceptibilities of isolated bacteria to various antibacterial
      agents and patients' characteristics. Of 383 strains that were isolated from
      specimen (mainly from sputum) and assumed to be bacteria causing in inflammation,
      381 strains were examined. The breakdown of the isolated bacteria were:
      Staphylococcus aureus 87, Streptococcus pneumoniae 80, Haemophilus influenzae 78,
      Pseudomonas aeruginosa (non-mucoid) 35, P. aeruginosa (mucoid) 9, Klebsiella
      pneumoniae 15, Moraxella subgenus Branhamella catarrhalis 30, etc. Of 87 S.
      aureus strains, those with 2 microg/mL or less of MIC of oxacillin (methicillin
      sensitive S. aureus: MSSA) and those with 4 microg/mL or more of MIC of oxacillin
      (methicillin-resistant S. aureus: MRSA) were 40 (46.0%) and 47 (54.0%) strains,
      respectively. Against MSSA, imipenem had the most potent antibacterial activity
      and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA,
      vancomycin showed the most potent activity and inhibited the growth of all the
      strains at 1 microg/mL. Arbekacin (ABK) also showed the potent activity and its
      MIC90 was 2 microg/mL. Carbapenems showed the most potent activities against S.
      pneumoniae and inhibited the growth of all the strains at 0.25-0.5 microg/mL.
      Cefozopran (CZOP) also had a preferable activity (MIC90: 1 microg/mL) and
      inhibited the growth of all the strains at 2 microg/mL. In contrast, there were
      high-resistant strains (MIC: 128 microg/mL or more) for ABK (2.5%), erythromycin
      (37.5%), and clindamycin (38.8%). Against H. influenzae, levofloxacin showed the
      most potent activity and inhibited the growth of all the strains at 0.125
      microg/mL. Meropenem showed the most potent activity against P. aeruginosa
      (mucoid) and inhibited the growth of all the strains at 2 microg/mL. Against P.
      aeruginosa (non-mucoid), amikacin (AMK) had the most potent activity and its
      MIC90 was 4 microg/mL. The activity of CZOP against the non-mucoid type also was
      preferable and its MIC90 was 8 microg/mL. Against K. pneumoniae, CZOP,
      cefmenoxime, cefpirome, flomoxef were the most potent activity and inhibited the
      growth of all the strains at 0.063 microg/mL. Also, all the agents generally
      showed a potent activity against M. (B.) catarrhalis and the MIC90 of them were 4
      microg/mL or less. The approximately half the number (57.0%) of the patients with
      respiratory infection were aged 70 years or older. Bacterial pneumonia and
      chronic bronchitis accounted for 50.8% and 23.8% of all the respiratory
      infection, respectively. The bacteria frequently isolated from the patients with
      bacterial pneumonia were S. aureus (21.6%), S. pneumoniae (24.7%) and H.
      influenzae (20.1%). S. aureus (20.9%), S. pneumoniae (16.1%), and H. influenzae
      (16.1%) also were relatively frequently isolated from the patients with chronic
      bronchitis. Before the drug administration, the bacteria frequently isolated from
      the patients were S. pneumoniae (22.3%) and H. influenzae (25.1%). The bacteria
      relatively frequently isolated from the patients treated with macrolides were P.
      aeruginosa and the isolation frequency was 43.5%.

PMID- 17180805
TI  - [Clinical investigation on administration method of gatifloxacin based on PK/PD
      theory].
AB  - There have not been sufficient clinical studies based on
      pharmacokinetics/pharmacodynamics (PK/PD) theory, on which many clinical doctors
      have recently focused. To consider the optimized administration method based on
      PK/PD theory for gatifloxacin (GFLX), which was one of the oral fluoroquinolone
      antibacterial, we influenzae investigated clinical efficacies and adverse events
      for pelvic inflammatory disease (PID) in giving GFLX daily 400 mg divided twice a
      day or four times a day. The number of leukocyte and the value of CRP were
      significantly reduced by chemotherapy in twice a day group, compared with four
      times a day group. We were able to measure the blood level in 4 cases. The
      AUC/MIC values for presumption causative bacteria (causative bacteria in both
      cases: Escherichia coli) in cured patients were 142.28 and 280.16, however, in
      therapy-failed patients, the AUC/MIC value to presumption causative bacterium
      were 4.10 (causative bacteria: Prevotella bivia) and 4.35 (causative bacteria:
      Pseudomonas aeruginosa). These results suggested the importance of the
      therapeutic method based on PK/PD theory.

PMID- 17180806
TI  - [Relationship between protein binding and antimicrobial activities of antibiotics
      against Streptococcus pneumoniae and Haemophilus influenzae].
AB  - Fifty isolates of Streptococcus pneumoniae and 42 isolates of Haemophilus
      influenzae were isolated from the blood of children admitted to pediatric wards
      of hospitals in subprefucture between January 1998 and December 2005. The
      susceptibilities were measured by a microbroth dilution method using a standard
      broth and a broth containing 4.5% albumin. Against S. pneumoniae, penicillin G,
      ampicillin, cefotaxime, ceftriaxone, panipenem, meropenem, vancomycin,
      cefditoren, cefcapene, cefteram, faropenem and tebipenem were used and against H.
      influenzae, ampicillin, piperacillin, cefotaxime, ceftriaxone, panipenem,
      meropenem, clavulanic acid/ amoxicillin, cefditoren, cefcapene, cefteram,
      faropenem and tebipenem were used. Against S. pneumoniae, tebipenem was the
      highest antimicrobial activity in oral antibiotics (MIC90; < or = 0.06 microg/ml)
      and panipenem showed the highest activity for intravenous antibiotics (MIC90; <
      or = 0.12 microg/ml). Against H. influenzae, cefditoren was the highest activity
      for oral antibiotics (MIC90; < or = 0.06 microg/ml) and meropenem showed the
      highest activity for intravenous antibiotics (MIC90; < or = 50.06 microg/ml). The
      MIC90s measured by albumin containing broth were higher than those measured by
      standard broth. Protein binding rates of ceftriaxone, cefditoren, and faropenem
      were greater than 90%, and the MIC90 of these antibiotics measured by albumin
      addition methods were over 4-fold higher than those measured by standard methods.

PMID- 17180807
TI  - Coconut fats.
AB  - In many areas of Sri Lanka the coconut tree and its products have for centuries
      been an integral part of life, and it has come to be called the "Tree of life".
      However, in the last few decades, the relationship between coconut fats and
      health has been the subject of much debate and misinformation. Coconut fats
      account for 80% of the fat intake among Sri Lankans. Around 92% of these fats are
      saturated fats. This has lead to the belief that coconut fats are 'bad for
      health', particularly in relation to ischaemic heart disease. Yet most of the
      saturated fats in coconut are medium chain fatty acids whose properties and
      metabolism are different to those of animal origin. Medium chain fatty acids do
      not undergo degradation and re-esterification processes and are directly used in
      the body to produce energy. They are not as 'bad for health' as saturated fats.
      There is the need to clarify issues relating to intake of coconut fats and
      health, more particularly for populations that still depend on coconut fats for
      much of their fat intake. This paper describes the metabolism of coconut fats and
      its potential benefits, and attempts to highlight its benefits to remove certain
      misconceptions regarding its use.

PMID- 17180808
TI  - Selection of students to medical school.

PMID- 17180809
TI  - Screening for gestational diabetes mellitus: the Sri Lankan experience.
AB  - OBJECTIVE: To evaluate tests used for screening and confirmation of gestational
      diabetes mellitus (GDM) in Sri Lanka. METHODS FIELD BASED: Consecutive pregnant
      women in Homagama DDHS area (n = 853), were assessed for risk factors and
      subjected to random and postprandial urinary Benedict's and Dipstick tests,
      fasting and 2 hour post 75 g glucose capillary blood glucose (FBG and 2hBG) which
      were validated against 75 g oral glucose tolerance test (OGTT) performed at 24-28
      weeks (WHO criteria). HOSPITAL BASED: Retrospective analysis of consecutive high
      risk women (n = 999) and prospective study of randomly selected GDM women (n =
      66) to assess predictive value of the OGTT. RESULTS FIELD BASED: Sensitivity and
      specificity respectively of random urine Benedict's, 10%, 99.2%; postprandial
      urine Benedict's, 52.2%, 94.5%; postprandial urine Dipstick, 68.7%, 90%;
      capillary FBG threshold 4.1 mmol/l, 62.6%, 73%; capillary 2hBG threshold 7.2
      mmol/l, 98.5%, 95.2%; risk factors, 93.1%, 22.2%. HOSPITAL BASED: OGTT-11.6% lag
      curves, 16.3% abnormal, FPG accuracy at 4.7mmol/l; predictive value of 2 hPG > or
      = 8.9 mmol/l for insulin treatment-sensitivity 97.2%, specificity 71.4%.
      CONCLUSIONS: Current practice of random urine testing in community screening for
      gestational diabetes is unreliable, and glucose specific postprandial urine test
      improves sensitivity. FPG is unsuitable for screening, the 2 hour post 75 g blood
      glucose at a threshold of > 7.2 mmol/l is sensitive and specific. In laboratory
      confirmation using 75 g OGTT the fasting plasma glucose has low predictive value,
      2 hour test performed alone is liable to false positives and 2 hour glucose > 8.9
      mmol/l following a peak at 1 hour suggests the need for insulin treatment.

PMID- 17180810
TI  - Factors associated with home deliveries in Thampalakamam, Trincomalee.
AB  - INTRODUCTION: In Sri Lanka, more than 95% of women deliver in hospital. There is
      regional variation in the rate of home deliveries, and in some areas a
      significant number of mothers deliver at home. OBJECTIVE: The objective of the
      present study was to identify the factors associated with home deliveries in
      Thampalakamam, Trincomalee. METHODOLOGY: Ours was a community based, exploratory
      type of case control study. Cases were home deliveries during the period from Jan
      1, 2000 to Dec 31, 2002 in Thampalakamam Divisonal Director of Health Services
      (DDHS) area. Controls were institutional deliveries among women residing in
      Thampalakamam DDHS area during the same period. A total of 139 cases and 278
      controls were identified for this study. Data was collected at the household
      level using an interviewer-administered questionnaire. RESULTS: The following
      factors were found to have strong association with home deliveries: being a
      Muslim (OR = 33.0, 95% CI 16.8-64.8), low (< grade 5) maternal education (OR =
      3.5, 95% CI 1.8-6.6), parity more than 3 (OR = 3.2, 95% CI 1.5-6.6) not being
      visited by a public health midwife (OR = 2.4, 95% CI 0.8-6.9), not being seen by
      a medical officer during the antenatal period (OR = 7.0, 95% CI 0.6-83.3). Lack
      of transport (35.5%) was mentioned as main reason for home deliveries by the
      women. Of the home deliveries 95% were assisted by a traditional birth attendant.
      CONCLUSIONS: Poor education of women and deficiencies in the delivery of
      antenatal care were found to be important risk factors for home deliveries.

PMID- 17180811
TI  - Nutritional status of children under five in three state foster care institutions
      in Sri Lanka.
AB  - This study evaluated the prevalence of protein energy malnutrition (PEM) in
      children under five years (n = 52), in three randomly selected, State operated
      foster care institutions in Sri Lanka. The prevalence of PEM, was (51.9%),
      underweight (63.5%) and wasting (25.0%) was found to be considerably higher than
      the national prevalence (13.5%, 29.4%, 14.0%, respectively). Based on this
      preliminary evidence, it is recommended that a study representative of all
      institutionalised children in both State and private facilities be conducted to
      identify deficiencies and recommend improvements to institutional care in Sri
      Lanka.

PMID- 17180812
TI  - Cushing syndrome due to an adrenal phaeochromocytoma.

PMID- 17180813
TI  - Herniation of a hamartomatous growth of the liver in an infant masquerading as a
      cardiac tumour.

PMID- 17180814
TI  - Fatal Burkholderia pseudomallei septicaemia.

PMID- 17180815
TI  - Endoscopic snare polypectomy of a periampullary neoplasm.

PMID- 17180816
TI  - Disseminated tuberculosis following BCG vaccination.

PMID- 17180817
TI  - A structured training programme in laparoscopic cholecystectomy.

PMID- 17180818
TI  - Myocarditis in three patients with dengue virus type DEN 3 infection.

PMID- 17180819
TI  - Avian influenza.

PMID- 17180820
TI  - Ariel Sharon's illness: should we dedicate a medical journal issue to a single
      case study?

PMID- 17180821
TI  - The health of leaders: information, interpretation and the media.

PMID- 17180822
TI  - When leaders become ill.

PMID- 17180823
TI  - Caring for VIPs in the hospital: the ethical thicket.

PMID- 17180824
TI  - Transparency with respect to the health of political leaders.

PMID- 17180825
TI  - Problems and questions regarding the treatment of political leaders.

PMID- 17180826
TI  - Mass-mediated medicine.

PMID- 17180827
TI  - Patient's condition--severe but stable. The press and the medical community:
      mutual expectations surrounding the health of national leaders.
AB  - A value system that espouses the right of an individual to guard his privacy has
      moral, theoretical and practical validity, while equal weight must be given,
      morally, conceptually and socially, to a concept that extols freedom of
      expression and the public's right to know. The built-in contradiction between
      these two schools of thought is expressed, inter alia, in the inter-relationship
      between the media and the medical community when the health of a national leader
      ceases to be his private affair and becomes the legitimate concern of the public.
      In Israel, no set rules exist regarding how such situations are reported. This
      article aims to suggest such a procedure.

PMID- 17180828
TI  - Echocardiography as a tool in the evaluation of conditions with a high likelihood
      of cardiogenic embolism.

PMID- 17180829
TI  - Anticoagulants to prevent stroke occurrence and worsening.

PMID- 17180830
TI  - Anticoagulation for stroke prevention.

PMID- 17180831
TI  - Trombolysis in acute stroke.
AB  - BACKGROUND: Rapid restoration of cerebral blood flow is the principle goal of
      acute ischemic stroke therapy. Intravenous recombinant tissue plasminogen
      activator is an effective therapy for acute ischemic stroke. It has been
      available in the United States for over a decade and was approved for use in
      Israel at the end of 2004. OBJECTIVES: To assess the implementation of
      intravenous rt-PA in routine clinical care at our center after its formal
      approval in Israel, and the therapeutic and logistic implications for reperfusion
      therapy for acute ischemic stroke in Israel. METHODS: Patients with acute
      ischemic stroke admitted between January 2005 and June 2006 who were treated with
      intravenous rt-PA or endovascular-based reperfusion were reviewed.
      Implementation, timing, safety and clinical outcomes were assessed. RESULTS:
      Forty-six patients received reperfusion therapy (37 with intravenous rt-PA and 9
      with endovascular-based therapy), corresponding to 4.0% of ischemic stroke
      patients in 2005 and a projection of 6.2% in 2006. The mean age of intravenously
      treated patients was 67 years (range 22-85 years), median baseline NIHSS score
      was 14 (25-75%, 10-18) and the median 'onset to drug time' was 150 minutes (25
      75%, 120-178). Symptomatic intracerebral hemorrhage and orolingual angioedema
      each occurred in one patient (2.7%). Significant clinical improvement occurred in
      54% of treated patients, and 38% of patients were independent at hospital
      discharge. CONCLUSIONS: The use of reperfusion therapy for acute ischemic stroke
      has increased in our center after the formal approval of rt-PA therapy to over
      5%, with 'onset to drug time', safety and outcome after intravenous rt-PA
      treatment comparing favorably with worldwide experience. A prerequisite for the
      implementation of effective reperfusion therapy and expansion of the proportion
      of patients treated nationwide is the establishment of a comprehensive
      infrastructure.

PMID- 17180832
TI  - Novel therapies for acute ischemic stroke.
AB  - Acute ischemic stroke is one of the leading causes of mortality and chronic
      disability in the western world. Yet, despite the enormous socioeconomic burden
      that it imposes, therapies to combat AIS are not widely available. Moreover,
      revascularization of the ischemic tissue with tissue plasminogen activator, the
      only FDA-approved therapy for AIS, is hampered by a very narrow therapeutic time
      window and is only used in a minority of patients. Cerebral ischemia leads to
      brain damage caused by several pathologic mechanisms that can potentially be
      blocked by neuroprotective drugs that aim to salvage the ischemic penumbra.
      However, despite numerous clinical trials, no single drug candidate has proved
      efficacious in AIS. The current situation calls for novel therapeutic strategies
      to be used in acute ischemic stroke. This review surveys some of these novel and
      promising cutting edge therapies.

PMID- 17180833
TI  - Patent foramen ovale: echocardiographic evaluation and clinical implications.

PMID- 17180834
TI  - Stroke in congenital heart disease and patent foramen ovale.
AB  - Congenital heart disease is usually regarded as an esoteric field of medicine,
      dealt with primarily by dedicated specialists. However, over the last two
      decades, increased attention has been given by the medical profession, the media
      and the general public to the possible association between a minor and common
      congenital heart defect, namely patent foramen ovale, and stroke. In recent
      months, unusual and unfortunate circumstances have made this topic one of the
      most fiercely debated medical issues in Israel. It is the belief of the authors
      of this paper that the association of PFO and stroke can be better understood if
      the PFO is viewed as part of the broader context of congenital heart disease, and
      as such it will be presented. Paradoxical embolism is a mechanism of stroke
      unique to congenital heart disease. The direction and volume of shunted blood in
      various conditions have a central role in determining the risk of stroke, as will
      be explained. With this basic knowledge in mind, we shall critically assess the
      potential role of PFO in stroke patients, suggesting that each case be evaluated
      individually using the above-mentioned principles. Conditions that enhance the
      formation of clot or other embolic material will be discussed briefly. The review
      will conclude with the various treatment options and our center's own experience
      with this challenging topic.

PMID- 17180835
TI  - Cerebral amyloid angiopathy--a disease or age-related condition.
AB  - Cerebral amyloid angiopathy is characterized by deposition of amyloid in the
      walls of leptomeninged and cerebral blood vessels. Its most common form, sporadic
      CAA that results from deposition of beta-amyloid peptide, which is the subject of
      this short review, is present in virtually all cases of Alzheimer disease and is
      also common among non-demented subjects where its prevalence increases with age.
      Stroke due to massive cerebral lobar hemorrhage is the main clinical presentation
      of CAA, but transient neurologic symptoms due to microhemorrhages may also occur.
      CAA is also a risk factor for cerebral infarction and there is increasing
      evidence that CAA contributes to cognitive impairment in the elderly, usually in
      association with white matter abnormalities on imaging. Although the definitive
      diagnosis of CAA is neuropathologic, reliable diagnosis can be reached
      clinically, based on the occurrence of strictly lobar hemorrhages, particularly
      in the cortico-subcortical area when using gradient-echo or T2*-weighted magnetic
      resonance imaging. Experimental studies have shown that the origin of the
      vascular amyloid is neuronal, and that age-related degenerative changes in the
      vessel walls prevent its clearance from the brain along perivascular spaces and
      promote Abeta aggregation and CAA formation. The entrapped Abeta aggregates are
      toxic to various vascular wall components, including smooth muscle cells,
      pericytes and endothelial cells, leading to their eventual destruction and
      predisposition of the vessel wall to rupture and hemorrhage. However, more
      research is necessary to decipher the mechanism of CAA formation and its relation
      to cognitive decline in the elderly.

PMID- 17180836
TI  - Recombinant factor VIIa for rapid reversal of anticoagulant effect in patients
      with intracranial hemorrhage: the Israeli experience and review of the
      literature.

PMID- 17180837
TI  - Treatment of acute intracerebral hemorrhage.

PMID- 17180838
TI  - Spontaneous intracerebral hemorrhage: to operate or not to operate, that's the
      question.
AB  - BACKGROUND: The occurrence of a spontaneous intracerebral hemorrhage in Israel's
      Prime Minister attracted the scrutiny of local and international media on
      neurosurgeons as they made therapeutic decisions. In the ensuing public debate,
      it was suggested that extraordinary measures (surgical treatment) were undertaken
      only because of the celebrity of the patient. OBJECTIVES: To evaluate the
      criteria used to select surgical versus medical management for SICH. METHODS: We
      retrospectively reviewed the files of 149 consecutive patients with SICH admitted
      to our medical center from January 2004 through January 2006. Their mean age was
      66 (range 3-92 years), and 62% were male. SICH localization was lobar in 50% of
      patients, thalamus in 23%, basal ganglia in 15%, cerebellum in 13%,
      intraventricular in 6%, and pontine in 1%. Mean admission Glasgow Coma Score was
      9 (range 3-15). Risk factors included hypertension (74%), diabetes mellitus
      (34%), smoking (14%) and amyloid angiopathy (4%). Fifty percent of patients were
      on anticoagulant/antiplatelet therapy, including enoxaparin (3%), warfarin (7%),
      warfarin and aspirin (9%), or aspirin alone (34%). RESULTS: Craniotomy was
      performed in 30% of patients, and ventriculostomy alone in 3%. Rebleed occurred
      in 9% of patients. Six months after treatment 36% of operated patients were
      independent, 42% dependent, and 13% had died. At 6 months, 37% of non-operated
      patients were independent, 15% dependent, and 47% had died. CONCLUSIONS: One
      third of the SICH patients, notably those who were experiencing ongoing
      neurologic deterioration and had accessible hemorrhage, underwent craniotomy. The
      results are good, considering the inherent mortality and morbidity of SICH.

PMID- 17180839
TI  - Vegetative state.
AB  - Nowadays more and more patients survive severe brain injury, whether due to
      traumatic or other causes, owing to the technological advances in medicine. Added
      to this is a better understanding of pathophysiologic processes, the quality and
      availability of emergency medicine, and increased medical knowledge in the field.
      More patients are regaining consciousness than previously. Recovery of functional
      ability ranges from those still requiring significant nursing care to those able
      to function independently in activities of daily living. These changes in the
      levels of consciousness and function can also occur after very long periods of
      vegetative state. In our personal experience in the hospital, in 2004, 81% of
      patients in a post-traumatic vegetative state recovered some level of
      consciousness.

PMID- 17180840
TI  - The cost of health care.

PMID- 17180841
TI  - Sanford School of Medicine of the University of South Dakota update.

PMID- 17180842
TI  - Why does Dr. Bareis think, "almost all physicians abhor abortion?".

PMID- 17180843
TI  - Case report: sirolimus associated interstitial lung disease.

PMID- 17180844
TI  - The 2005 Annual Report of the Regional Infant and Child Mortality Review
      Committee.
AB  - The annual report of the Regional Infant and Child Mortality Review Committee
      (RICMRC) is attached. This Committee has as its mission the review of infant and
      child deaths so that information can be transformed into action to protect young
      lives. The 2005 review area includes South Dakota's Minnehaha, Turner, Lincoln,
      Moody, Lake, McCook, Union, Hansen, Miner, and Brookings counties. Although there
      was only one death meeting the criteria of the Sudden Infant Death Syndrome
      (SIDS) in our region, there were four infant deaths associated with soft, unsafe,
      sleeping surfaces where asphyxia could not be excluded. We need to continue to
      promote the "Back to Sleep" campaign message of not only placing infants to sleep
      on their backs, but also making sure infants are put down to sleep on safe, firm,
      sleeping surfaces. Nine of ten accidental deaths were related to motor vehicle
      crashes (versus three in 2004). Unlike previous years, there were no fire-related
      deaths. In 2005 there were two child abuse related homicides and one teenage
      suicide. The RICMRC invites other communities to join in its efforts to review
      deaths to prevent potential life threatening hazards to children in their local
      environs.

PMID- 17180845
TI  - Insulin in the adult intensive care unit.

PMID- 17180846
TI  - Preventing hospital payment errors.

PMID- 17180847
TI  - Physician communications program.

PMID- 17180848
TI  - It wasn't my fault....

PMID- 17180850
TI  - A doctor's story.

PMID- 17180849
TI  - Postmenopausal osteoporosis management--a Wegner Health Science Information
      Center information update. November 2006.

PMID- 17180851
TI  - The state of childhood asthma, United States, 1980-2005.

PMID- 17180852
TI  - [Legal basis of licensing of medical units and establishments of the Russian
      Federation MD].

PMID- 17180853
TI  - [Surgical aid to wounded in counter-terrorist operations in the Northern
      Caucasus: specialized surgical aid in the medicals establishments of 2-3
      echelones (sixth message)].

PMID- 17180854
TI  - [Surgical service aid to wounded in the counter-terrorist in the Northern
      Caucasus: coming into being of military field surgery of local wars and armed
      conflicts (seventh message, final)].

PMID- 17180855
TI  - [Results of usage of temporary prosthetics in cases of combat injuries of
      extremities].
AB  - The comparative analyzes of the results of usage of temporary prosthetics (TP) of
      injured main arteries during the war in Afghanistan (1979-1989) and counter
      terrorist operations in the Northern Caucasus (1994-1996, 1999-2002) has been
      carried out. The development of new models of temporary prosthetics of vessels
      has been experimentally substantiated. In Afghanistan the two-staged usage of TP
      was made along with the amputation of extremities in 35,1% of cases and in the
      Northern Caucasus - in 15,0%. The reason for that was the considerable reduction
      of terms of evacuation of wounded. The average terms of presence of TP in the
      arteries in Afghanistan were 26,2+/-4,0 hours and in the Northern Caucasus -
      18,1+/-3,4 hours. During a series of experiments on comparative testing of
      efficiency of three types of TP it was determined that prosthetics made of
      armored silicone (10,1+/-0,6 hours)and, especially made of enlarged micropored
      polytetraftoraethylen (11,5 +/-0,6 hours) are thrombosed slower comparing to
      polyclorvinil tube from the blood transfusion system (7,9+/-0,7 hours).

PMID- 17180856
TI  - [Clinical experience of usage of neurostimulator in regionar anesthesia].
AB  - The elaboration of more reliable and simple methods of transmitted and plexus
      anestesias has provided a wide clinical usage of regionar anestesia (RA) during
      the operations on extremities. The creation of devices to identificate (locate)
      nerval bearer and plexes was also an important factor for increasing quantity of
      RA. For such identification we use the portable "Innervator 232" neurostimulator
      manufactured by "Fisher & Paykel Ltd.", New Zealand. Successful conduction of
      transmitted and plexus anesthesia depends a lot on anesthesiologist's knowledge
      of anatomy-topography location of nerval bearer and plexes, precise fulfillment
      of anesthesia, manual capabilities of physician and obtaining a paresthesia or
      muscular contraction during the identification of nerval bearer with the help of
      neurostimulator. RA is secure, effective, and provides less risk for a patient.
      With neurostimulation the amount of successful anesthesias increases up to 98%.
      The neurostimulator is easy to use, clinically effective in emergency and planned
      surgeries for identification of nerval bearer and plexes.

PMID- 17180857
TI  - [Surgical infection in drug dependands: determination of severity degree and
      treatment-tactical characteristics].
AB  - Basing on examination of 187 opium taking patients with surgical infection, the
      method of identification of infection severity degree and treatment-tactical
      policy of delivery of specialized medical care for those patients have been
      developed. The probable positive result of the proposed method is 90,4%. The rest
      9,6% is a true negative result or a pure error of the proposed method of
      dentification of infection severity degree. The usage of the developed method in
      every day activity of surgical hospitals provides the possibility of differential
      approach to reaching the treatment-tactical goals revealing the patients with
      light degree of surgical infection and favorable outcome, medium degree of
      surgical infection and relatively favorable outcome, high degree of surgical
      infection and relatively unfavourible outcome and extremely high degree and
      unfavourible outcome.

PMID- 17180858
TI  - [The role of antioxidants in treatment of combined cardiorespiratory pathology].

PMID- 17180859
TI  - [Endovideosurgery in the war surgery].

PMID- 17180860
TI  - [Comparative effciency of bakloferon and tolperizon central muscle relaxants in
      complex therapy of back pain].

PMID- 17180861
TI  - [Distinguished surgeon and organizer of military health care (the 130th
      anniversary of N.N.Burdenko].

PMID- 17180862
TI  - [The war surgery--yesterday and today].

PMID- 17180863
TI  - [The Keller A. A. contribution to medical geography and ecology].

PMID- 17180864
TI  - ["I have passed my examinations during the war" (interview with captain of
      medical service (retired) professor M.K. Kuzmin (interview)].

PMID- 17180865
TI  - Are neurodegenerative disorder and psychotic manifestations avoidable brain
      dysfunctions with adequate dietary omega-3?
AB  - The present mismatch between what our brain needs, and the modern diet neglects
      our marine heritage. Last century, the priority in nutrition and food production
      was to achieve a high protein diet and somatic growth and function. The dietary
      content of omega-3 (N-3) required by the brain was neglected although evidence
      for the essentiality of certain fatty acids was published in 1929 and
      specifically re-affirmed for omega 3 in the brain in the 1970s. Cognitive decline
      with age and neurodegenerative disorder with dementia are now rising. This review
      describes signs of N-3 deficit in Alzheimer and Parkinson Disease, where maximum
      change involves the primary sites: olfactory cortex and the hippocampus. The
      olfactory agnosia observed in schizophrenia supports an N-3 deficit as does a
      reduction of key ologodendrocyte- and myelin-related genes in this disorder and
      affective disorder, where a rise in dementia accords with a deficit of N-3 also
      in this disorder. N-3 normalizes cerebral excitability at all levels. That the
      two disorders are localized at the extremes of excitability, is supported by
      their opposing treatments: convulsant neuroleptics and anti-epileptic
      antidepressants. An adequate N-3 diet will probably prevent most psychotic
      episodes and prove that neurodegenerative disorder with dementia is also to a
      large extent not only preventable but avoidable.

PMID- 17180866
TI  - Subtle changes in the ageing human brain.
AB  - Subtle changes in the human brain constitute a third element in addition to
      plaques and tangles as markers of vulnerability to Alzheimer's disease (AD).
      Neurofibrillary tangle (NFT) distribution shows the closest relationship to the
      severity of dementia. Two features of the distribution (regional selectivity and
      columnar clustering) provide clues about the structural changes due to normal
      ageing that may precede tangle formation. It is hypothesized that the columnar
      organization of the cortex, determines the pattern of pathological spread in AD
      and, consequently, the pattern of function loss. Minicolum thinning occurs in
      normal ageing and echoes the selective regional distribution of NFT formation in
      AD. NFT vulnerability appears to emerge from hierarchical variation in neural
      plasticity associated with the hierarchical variation in size and spacing of mini
      and macro-columns in the cortex. Regional differences may involve regional
      variation in gene expression. Dietary Omega 3 fatty acid intake has been shown to
      have neuroprotective effects on the cytoarchitectural features that contribute to
      this cortical hierarchy.

PMID- 17180867
TI  - Prevention of dementia: a role for B vitamins?
AB  - Dementia has reached epidemic proportions, with an estimated 4.6 million new
      cases worldwide each year. With an aging world population the prevalence of
      dementia will increase dramatically in the next few decades. Of the predicted 114
      million who will have dementia in 2050 about three-quarters will live in the less
      developed regions. Although strongly age -related, dementia is not an inevitable
      part of aging but is a true disease caused by exposure to several genetic and non
      genetic risk factors. Prevention will be possible when the non genetic risk
      factors have been identified. Apart from age, more than 20 non-genetic risk
      factors have been postulated but very few have been established by randomised
      intervention studies. Elevated blood concentrations of total homocysteine and low
      normal concentrations of B vitamins (folate, vitamins B-12 and B-6) are candidate
      risk factors for both Alzheimer's disease and vascular dementia. A review of the
      literature up to the end of 2005 shows the following. Seventy seven cross
      sectional studies on > 34,000 subjects and 33 prospective studies on > 12,000
      subjects have shown associations between cognitive deficit or dementia and
      homocysteine and/or B vitamins. Biologically plausible mechanisms have been
      proposed to account for these associations, including atrophy of the cerebral
      cortex, but a definite causal pathway has yet to be shown. Raised plasma total
      homocysteine is a strong prognostic marker of future cognitive decline, and is
      common in world populations. Low-normal concentrations of the B vitamins, the
      main determinant of homocysteine concentrations, are also common and occur in
      particularly vulnerable sections of the population, such as infants and the
      elderly. Large-scale randomised trials of homocysteine-lowering B vitamins are
      needed to see if a proportion of dementia in the world can be prevented.

PMID- 17180868
TI  - Nutrigenomic approaches to study the effects of n-3 PUFA diet in the central
      nervous system.
AB  - Deficiencies in essential, mainly omega-3 and omega-6 (n-3, n-6) long chain
      polyunsaturated fatty acids (LC-PUFA) result in visual and cognitive impairment
      and disturbances in mental functions in animals and could be the main reason for
      the increasing incidence of different mental disorders in humans. Traditional
      approaches cannot give us a detailed picture on how dietary lipids exert their
      effects, because they focus on only a few genes or biomarkers. Dietary lipids not
      only influence the biophysical state of the cell membranes but, via direct and
      indirect routes, they also act on multiple pathways including signalling and gene
      and protein activities. Therefore, to understand the molecular basis of the
      effects and roles of n-3 PUFA in the central nervous system global screening
      techniques such as DNA- or protein microarrays were used to assess the changes,
      in a global way, at the transcriptome and at the proteome level. With DNA
      microarrays we found that cholesterol and fish oil (high in PUFA) diets altered
      the expression of several genes involved in raft formation and membrane
      protrusions. By using protein microarrays we detected a decreased concentration
      of protein kinase C beta, gamma, phospholipase C gamma and other changes in the
      expression level of proteins involved in the signal transduction pathway in the
      brain in response to high cholesterol diet. Besides the known cellular effects of
      lipid nutritions (changing eicosanoid make up, effects on membrane fluidity and
      raft stability) it is now evident that dietary lipids influence gene and protein
      activity levels, protein modifications and probably play important role in
      modulating protein aggregation.

PMID- 17180869
TI  - The role of dietary fatty acids in children's behaviour and learning.
AB  - A growing awareness and understanding of the profiles of local children in County
      Durham, UK, experiencing learning and behavioural difficulties throughout the
      education system, has resulted in a number of school based nutritional
      intervention studies being undertaken. Evidence suggests that some children and
      young adults with developmental difficulties have a deficiency of particular
      omega 3 and omega 6 polyunsaturated fatty acids and supplementation with these
      nutrients can have an impact on their behaviour, concentration and performance on
      standardised assessments. The first randomised placebo controlled trial to be
      carried out on children in Durham with developmental coordination disorder has
      demonstrated significant effects of fatty acid supplementation on behaviour,
      reading and spelling performance. We are conducting further scientific studies
      within Durham and neighbouring Authorities in the North of England to be
      published at a future time. We have also carried out a number of open label
      treatment studies within schools to help us understand better the role that
      nutritional intervention can play across a broader range of age groups and
      abilities. The results suggest positive outcomes for a substantial proportion of
      children who are more able to engage with the educational opportunities presented
      to them. This is an important finding to be shared with educationalists, health
      professionals and importantly the parents.

PMID- 17180870
TI  - Docosahexaenoic acid protects from amyloid and dendritic pathology in an
      Alzheimer's disease mouse model.
AB  - Genetic data argues that Alzheimer's disease (AD) can be initiated by aggregates
      of a 42 amino acid beta amyloid peptide (Abeta42). The Abeta aggregates, notably
      small oligomer species, cause a cascade of events including oxidative damage,
      inflammation, synaptic toxicity and accumulation of intraneuronal inclusions;
      notably neurofibrillary tangles. Cognitive deficits are likely to begin with a
      failure of synaptogenesis and synaptic plasticity with dendritic spine loss and
      dying back of dendritic arbor. This is followed by neuron loss in key areas
      involved in learning and memory. Significant prevention or delay of clinical
      onset may be achievable by modifying environmental risk factors that impact the
      underlying pathogenic pathways. Because low fish intake and low blood levels of
      the marine lipid, docosahexaenoic acid (DHA) have been associated with increased
      AD risk we have tested the impact of depleting or supplementing with dietary DHA
      on AD pathogenesis in transgenic mice bearing a mutant human gene known to cause
      AD in people. We reported that even with intervention late in life dietary DHA
      depletion dramatically enhanced oxidative damage and the loss of dendritic
      markers, while DHA supplementation markedly reduced Abeta42 accumulation and
      oxidative damage, corrected many synaptic deficits and improved cognitive
      function. Loss of brain DHA was exacerbated in mice expressing the mutant human
      AD transgene, this is consistent with evidence for increased oxidative attack on
      DHA oxidation in AD. Treatment with the curry spice extract curcumin, a
      polyphenolic antioxidant that inhibits AP aggregation, has been strongly
      protective in the same mouse model. Many Western diets are typically deficient in
      DHA and low in polyphenolic antioxidant intake. These and other data argue that
      increasing dietary intake of both DHA and polyphenolic antioxidants may be useful
      for AD prevention.

PMID- 17180871
TI  - Docosahexaenoic acid: a pluripotent molecule acting as a membrane fluidizer, a
      cellular antioxidant and a modulator of gene expression.

PMID- 17180872
TI  - Docosahexaenoic acid in neural signaling systems.
AB  - Docosahexaenoic acid has been conserved in neural signalling systems in the
      cephalopods, fish, amphibian, reptiles, birds, mammals, primates and humans. This
      extreme conservation, despite wide genomic changes over 500 million years,
      testifies to a uniqueness of this molecule in the brain. The brain selectively
      incorporates docosahexaenoic acid and its rate of incorporation into the
      developing brain has been shown to be greater than ten times more efficient than
      its synthesis from the omega 3 fatty acids of land plant origin. Data has now
      been published demonstrating a significant influence of dietary omega 3 fatty
      acids on neural gene expression. As docosahexaenoic acid is the only omega 3
      fatty acid in the brain, it is likely that it is the ligand involved. The
      selective uptake, requirement for function and stimulation of gene expression
      would have conferred an advantage to a primate which separated from the
      chimpanzees in the forests and woodlands and sought a different ecological niche.
      In view of the paucity of docosahexaenoic acid in the land food chain it is
      likely that the advantage would have been gained from a lacustrine or marine
      coastal habitat with access to food rich in docosahexaenoic acid and the
      accessory micronutrients, such as iodine, zinc, copper, manganese and selenium,
      of importance in brain development and protection against peroxidation. Land
      agricultural development has, in recent time, come to dominate the human food
      chain. The decline in use and availability of aquatic resources is not considered
      important by Langdon (2006) as he considers the resource was not needed for human
      evolution and can be replaced from the terrestrial food chain. This notion is not
      supported by the biochemistry nor the molecular biology. He misses the point that
      the shoreline hypothesis is not just dependent on docosahexaenoic acid but also
      on the other accessory nutrients specifically required by the brain. Moreover he
      neglects the basic principle of Darwinian evolution. The well documented greater
      efficiency of preformed docosahexaenoic acid for brain incorporation during
      development would have conferred a distinct survival advantage over those without
      it. All terrestrial mammals lost brain capacity in relation to advancing increase
      in body size. The rise in mental ill health and brain disorders, to replace all
      other costs in the European list of burdens of ill health, (Andlin Sobocki et
      al., 2005) raises interesting questions as to its association with the reduced
      availability and consumption of marine and fresh water products. The threat posed
      by the continued rise in brain disorders also raises questions of importance to
      present and future food and agricultural policies.

PMID- 17180873
TI  - The impact of diet and exercise on brain plasticity and disease.
AB  - Lifestyle involves our preference to engage in behaviors that can remarkably
      influence the fitness level of our body and brain. Dietary factors are a powerful
      means to influence brain function on a daily basis. We have shown that the
      consumption of a diet rich in saturated fat decreases learning and memory and
      increases metabolic distress. Conversely, diets supplemented either with omega-3
      fatty acids, vitamin E or the curry spice curcumin benefit cognitive function.
      Equally impressive is the action of exercise on cognitive function as documented
      by studies showing that exercise enhances learning and memory. The beneficial
      action of exercise on the brain can be used therapeutically to overcome the
      effects of consuming a poor diet. We suggest that the managed use of diet and
      exercise can help the brain to cope with several types of insults and ultimately
      benefit brain function.

PMID- 17180874
TI  - From genetics to epigenetics.
AB  - In the post human-genome area, the challenge is to derive details of heritable
      variation in relation to how human variation reflects adaptation to the different
      environments. Heterozygote advantage represents a superior genetic adaptation
      presumably explaining the presence of the allele at frequencies above those to be
      expected from a simple replacement of a homozygous lethal allele by mutation
      alone (Saugstad 1977a, 1975b, 1972). Mean birthweight of unaffected offspring of
      parents heterozygous for the phenylketonuria (PKU) allele averaged significantly
      above mean weight of all Norwegian births, rendering unaffected offspring more
      viable at birth and thus improving the chance for survival of the allele. A
      successful adaptation requires natural selection acting on that part of the body
      that makes a difference in survival. Skin colour variation is such a successful
      adaptation, for the North as opposed to the dark skins of the equator. Human
      Evolution in Africa and subsequent adaptations have enabled human survival all
      over the world with highly different light intensity (Jablonski & Chaplin 2000).
      That continuous variables, height, pubertal age and brain development, are
      multifactorially inherited and affected by epigenetic factors, was nicely
      demonstrated in the increase in height in Norway 1860-1960 with at the same time
      a reduction in pubertal age by 4yrs which may have affected the final stage in
      brain development. This created an increased need for brain food, N-3, to secure
      optimal brain function. Body growth is not brain growth. Given that the
      consumption of brain food (N-3) has declined to 20% only of the level 100yrs ago,
      what disorders are to be expected with an N-3 dietary deficit: in pregnancy,
      infancy and later in life? In this paper I discuss the significance of
      prepubertal selective pruning of excitatory synapses compared to delayed pruning
      and suggest relationships with brain disorders.

PMID- 17180875
TI  - Cortical plasticity and motor activity studied with transcranial magnetic
      stimulation.
AB  - For decades cortical representations of the parts of the body have been
      considered to be unchangeable. This view has changed radically during the past 20
      years using new tools designed to study plasticity in the adult human brain.
      Transcranial magnetic stimulation (TMS) is a valuable non-invasive technique for
      exploring the ability of the motor cortex to change during motor skill
      acquisition. Results obtained with TMS in neurological patients as well as in
      normal subjects demonstrate that cortical plasticity is a necessity for correct
      adaptation to the continuously changing environment. Topographical reorganization
      of the motor cortex depends on the types of movements performed by the subjects.
      During simple training, the cortical representation is enlarged, and it returns
      to its initial size when the task is overlearned. These transient modifications
      characterize simple motor training. Motor skills in which coordination of distal
      and proximal muscles, precision of the task and spatio-temporal constraints are
      associated, has a different impact on cortical reorganization. We propose that
      years of practice of a complex motor skill induces a new cortical topography that
      must be interpreted as structural plasticity which provides the capacity to
      execute a plastic behaviour instead of a stereotypical movement. We review the
      neuronal mechanisms underlying plasticity in different types of movement. We
      stress new emerging notions, such as overlap of cortical maps, and system
      dynamics at single neuron and network levels, to explain the reorganization of
      movement representations that encode motor skill. Dendritic arborizations as
      functional computing elements, newly generated neurons in adult brain, and
      plastic architectures of cortical networks operating as distributed functional
      modules are new hypotheses for structural plasticity.

PMID- 17180876
TI  - Involvement of the nitric oxide pathway in synaptic dysfunction following amyloid
      elevation in Alzheimer's disease.
AB  - Amyloid-beta (Abeta), a peptide thought to play a crucial role in Alzheimer's
      disease (AD), has attracted scientific interest with the aim of characterizing
      the mechanisms by which it is involved in AD pathogenesis. Abeta has been found
      to markedly impair hippocampal long-term potentiation (LTP), a widely studied
      cellular model of synaptic plasticity that is thought to underlie learning and
      memory. The overall purpose of this review is to define the role of the nitric
      oxide (NO)/cGMP/cAMP-regulatory element binding (CREB) pathway in beta-amyloid
      induced changes of basal neurotransmission and synaptic plasticity in the
      hippocampus, a structure within the temporal lobe of the brain critical for
      memory storage.

PMID- 17180877
TI  - Noradrenergic control of emotion-induced amnesia and hypermnesia.
AB  - Emotional memory encoding is associated with retrograde and anterograde episodic
      memory changes involving amnesia and hypermnesia, respectively. These effects are
      noradrenergic-dependent and reflect an interaction with emotional arousal and
      valence. Whereas anterograde amnesic effects most likely result from attentional
      capture by emotional arousal, retrograde amnesic and hypermnesic effects may
      reflect a valence-dependent filter mechanism that operates during emotional
      memory encoding and controls episodic memory access based upon behavioral
      significance. This filter mechanism may originnate in amygdala-hippocampal
      interactions that are modulated by both ascending locus coeruleus and descending
      prefrontal cortex inputs.

PMID- 17180878
TI  - A behavioral homeostasis theory of habituation and sensitization: II. Further
      developments and predictions.
AB  - Habituation may be viewed as a decremental behavioral change to iterative stimuli
      of little immediate relevance. It is observed from protozoa to humans, indicating
      its evolutionary significance. If habituation is interpreted as the process of
      filtering out unimportant repetitive stimuli, then how should sensitization be
      interpreted? The 'behavioral homeostasis theory' of these two behaviors is based
      on the notion that organisms at a high level of 'alertness' prior to experiencing
      a new iterative stimulus will show a large initial response followed by a
      decrement (habituation) if the stimulus is of little significance. Conversely,
      the same organism at a low level of 'alertness' will show a small initial
      response to the same stimulus followed by an increase in 'alertness' and a larger
      response to the next stimulus (sensitization) in order to receive enough
      information to assess its significance. Circadian rhythmicity is hypothesized to
      play a role in determining 'alertness' to a new iterative stimulus at any given
      time. The level of responsiveness in initial habituaters and sensitizers, as an
      asymptote is approached, is a balance between being too 'alert' to an unimportant
      stimulus and missing other significant stimuli, and being too 'un-alert' and
      missing a change in the relevance of the present iterative stimulus. The concept
      of 'behavioral homeostasis' includes behaviors beyond habituation and
      sensitization across phylogeny. It includes instinctive as well as learned, and
      group as well as individual behavior. Such behavioral homeostatic processes to
      optimize detection and assessment of constantly occurring external stimuli are
      critical for organism survival. Clinical implications of this theory are also
      examined.

PMID- 17180880
TI  - Polyunsaturated phosphatidylinositol and diacylglycerol substantially modify the
      fluidity and polymorphism of biomembranes: a solid-state deuterium NMR study.
AB  - One of the main biological systems that can be used as a model for studying the
      molecular mechanisms involved in membrane fusion is the formation of the nuclear
      envelope (NE). NE assembly to form the male pronucleus at fertilization occurs by
      binding of NE membrane precursor vesicles to chromatin and their fusion. MV1 is
      an NE precursor vesicle population of low density, highly enriched in
      [18:0/20:4]PI. The modification of [18:0/20:4]PI to [18:0/20:4]DAG leads to NE
      formation, and the depletion of MV1 from the total membrane precursors results in
      the inhibition of NE assembly. Here we show by 2H NMR studies of various
      physiologically relevant model membranes made of [18:0/20:4]PI, [18:0/20:4]DAG,
      and saturated and unsaturated PC that membranes of composition similar to MV1
      exhibit dramatically enhanced fluidity and non-lamellar structures, thus
      providing a possible explanation for the essential role of MV1 and the
      modification of PI to DAG in membrane precursor vesicles during NE assembly.

PMID- 17180881
TI  - Markedly raised intake of saturated and monounsaturated fatty acids in rats on a
      high-fat ketogenic diet does not inhibit carbon recycling of 13C-alpha
      linolenate.
AB  - Under various dietary and physiological conditions, carbon from alpha-linolenic
      acid (ALA) is extensively recycled into saturated and monounsaturated fatty
      acids. In this study we investigated whether carbon is still recycled from ALA
      when a dietary source of saturated and monounsaturated fatty acids is provided in
      excess. 13C-labeled ALA was given to rats consuming a high-fat ketogenic diet and
      to rats consuming a low-fat control diet. In rats on the ketogenic diet, 13C
      recycling from alpha-linolenate into several, but not all, saturated and
      monounsaturated fatty acids matched or exceeded that in the controls (P < 0.05).
      We conclude that carbon recycling into saturated and monounsaturated fatty acids
      persists when the main end products of ALA recycling are provided in excess,
      using a ketogenic diet.

PMID- 17180882
TI  - Effect of conjugated linoleic acid type, treatment period, and dosage on
      differentiation of 3T3 cells.
AB  - This study was conducted to determine effect of CLA and linoleic acid (LA) on
      cell differentiation, cellular glycerol-3-phosphate dehydrogenase (GPDH)
      activity, and FA accumulation in differentiating 3T3-L1 cells (3 isomers x 3
      treatment periods x 4 doses). The cells were cultured in 24-well plates for
      proliferation until confluence. Then they were treated with media containing 0,
      10, 35, or 70 mg/L (0, 35, 125, or 250 mmol/L, respectively) of LA, cis9,trans11-
      or trans10,cis12-CLA during early (day 0-2), intermediate and late (day 3-8), or
      overall (day 0-8) differentiation periods. Dexamethasone, methyl
      isobutylxanthine, and insulin were supplemented to the media only for the early
      period to induce the differentiation. On day 8 of postconfluence the cells were
      harvested for Oil Red O staining, analysis of GPDH activity, and determination of
      the FA Concentration. Cellular LA or CLA was found to accumulate in a dose
      response manner, mainly during the intermediate/late period. Treatment with
      trans10,cis12-CLA lowered (P < 0.05) GPDH activity and the concentration of FA
      including palmitic acid (16:0) and palmitoleic acid (16:1), especially during the
      intermediate/late and overall periods, or whenever a high dose of 70 mg/L was
      applied. This also resulted in a higher (P < 0.05) ratio of saturated FA to
      monounsaturated FA. Treatment with LA or cis9,trans11-CLA lowered cellular FA
      only when they applied during the early period at a dose of 70 mg/L. The results
      demonstrated that the inhibitory effects of CLA on differentiation, GPDH
      activity, and FA accumulation of 3T3-L1 cells are dependent on the isomer type,
      treatment period, and dose.

PMID- 17180879
TI  - Anticancer activity of natural and synthetic acetylenic lipids.
AB  - This review is a comprehensive survey of acetylenic lipids and their derivatives,
      obtained from living organisms, that have anticancer activity. Acetylenic
      metabolites belong to a class of molecules containing triple bond(s). They are
      found in plants, fungi, microorganisms, and marine invertebrates. Although
      acetylenes are common as components of terrestrial plants, fungi, and bacteria,
      it is only within the last 30 years that biologically active polyacetylenes
      having unusual structural features have been reported from plants, cyanobacteria,
      algae, invertebrates, and other sources. Naturally occurring aquatic acetylenes
      are of particular interest since many of them display important biological
      activities and possess antitumor, antibacterial, antimicrobial, antifouling,
      antifungal, pesticidal, phototoxic, HIV-inhibitory, and immunosuppressive
      properties. There is no doubt that they are of great interest, especially for the
      medicinal and/or pharmaceutical industries. This review presents structures and
      describes cytotoxic and anticancer activities only for more than 300 acetylenic
      lipids and their derivatives isolated from living organisms.

PMID- 17180884
TI  - [The ratio between the phasic and tonic components of the frontal midline theta
      rhythm in the attention test].

PMID- 17180883
TI  - Fatty acids and monoacylglycerols inhibit growth of Staphylococcus aureus.
AB  - Staphylococcus aureus causes a variety of human infections including toxic shock
      syndrome, osteomyelitis, and mastitis. Mastitis is a common disease in the dairy
      cow, and S. aureus has been found to be a major infectious organism causing
      mastitis. The objectives of this research were to determine which FA and
      esterified forms of FA were inhibitory to growth of S. aureus bacteria. FA as
      well as their mono-, di-, and triacylglycerol forms were tested for their ability
      to inhibit a human toxic shock syndrome clinical isolate (MN8) and two S. aureus
      clinical bovine mastitis isolates (305 and Novel). The seven most potent
      inhibitors across all strains tested by minimum inhibitory concentration analysis
      included lauric acid, glycerol monolaurate, capric acid, myristic acid, linoleic
      acid, cis-9, trans-11 conjugated linoleic acid, and trans-10, cis-12 conjugated
      linoleic acid. Some of these lipids were chosen for 48-h growth curve analysis
      with a bovine mastitis S. aureus isolate (Novel) at doses of 0, 20, 50, and 100
      microg/mL except myristic acid, which was tested at 0, 50, 100, and 200
      microg/mL. The saturated FA (lauric, capric, myristic) and glycerol monolaurate
      behaved similarly and reduced overall growth. In contrast, the polyunsaturated FA
      (linoleic and cis-9, trans-11 conjugated linoleic acid) delayed the time to
      initiation of exponential growth in a dose-dependent fashion. The results suggest
      that lipids may be important in the control of S. aureus during an infection.

PMID- 17180885
TI  - [Psychophysiological indices in six- to eight-year-old children under information
      load depending on anxiety as a stable individual characteristic].

PMID- 17180886
TI  - [The functional state of the sympathoadrenal system and the autonomic regulation
      of the cardiac rhythm in younger schoolchildren].

PMID- 17180887
TI  - [Correction of psychoemotional disturbances during pregnancy by the method of
      adaptive bioregulation with feedback according to EEG].

PMID- 17180888
TI  - [Comparative informativeness of neural network models in diagnostics of latent
      arterial hypertension on the basis of data on daily blood pressure monitoring].

PMID- 17180889
TI  - [Inhibition of calmodulin prevents spasms in autologous arterial bypass grafts
      during surgical treatment of ischemic heart disease].

PMID- 17180890
TI  - [Adaptive changes of heart activity to physical exercise in female physical
      education teachers in the European North].

PMID- 17180891
TI  - ["Negative phase" of the heart rate and stroke volume in young athletes after the
      Harvard Step Test].

PMID- 17180892
TI  - [The patterns of changes in the electromyographic profile of muscles in some gait
      disorders].

PMID- 17180893
TI  - [The dynamics of the psychophysiological state of navigator students during
      sailing].

PMID- 17180894
TI  - [Cerebral hemodynamic response to a maximal physical load].

PMID- 17180895
TI  - [Effect of an alternating magnetic field on the working capacity of human muscles
      under the conditions of local or general fatigue].

PMID- 17180896
TI  - [Relationships between hemorheology, erythrocyte metabolism, and von Willebrand
      factor in athletes and patients with peripheral arterial disease].

PMID- 17180897
TI  - [Changes in the protein composition of human saliva during modeling of
      psychological and emotional stress].

PMID- 17180899
TI  - [Adaptive changes in temperature sensitivity in humans under the conditions of
      cold, heat, and prolonged physical load].

PMID- 17180898
TI  - [Secretory activity of neutrophilic leukocytes in inflammatory periodontal
      diseases].

PMID- 17180900
TI  - [Etiology of endotoxin aggression and its role as an obligate pathogenetic factor
      in iridocyclites of different origins].

PMID- 17180901
TI  - [Changes in the lactogenic and stress hormone contents in the blood of pregnant
      women].

PMID- 17180902
TI  - [Plasticity of cortical structures under the conditions of neurological deficit
      accompanied by a disorder of hand movement. Modern approaches to rehabilitation].

PMID- 17180903
TI  - [Heart rate variability in subjects with different respiratory rates].

PMID- 17180904
TI  - [Effect of emotionally strained activity on sensory and secretory process in the
      oral cavity].

PMID- 17180905
TI  - [Correlation between electrophoretic mobility and aggregation rate of human red
      blood cells].

PMID- 17180906
TI  - [Derivatives of N-amidinoproline and their use in conventional and solid phase
      peptide synthesis].
AB  - N-Amidinoproline, a hybrid structure modeling key features of the Arg-Pro
      sequence, was synthesized. The activation of carboxyl group of free N
      amidinoproline was found to result in the formation of a cyclic side product,
      whose structure was confirmed by ESI MS, 1H NMR, and 13C NMR spectra. The
      preparation of N-(mesitylenesulfonylamidino)-L-proline using the
      mesitylenesulfonyl derivative of 2-methylisourea was demonstrated to be
      accompanied by partial racemization. The target product was synthesized by
      modification of N-amidinoproline by mesitylenesulfonyl chloride. The possibility
      of using N-amidinoproline in the N-terminal modification of a peptide chain was
      shown by the example of synthesis of an analogue of the 95-98 fragment of
      fibrinogen alpha chain.

PMID- 17180907
TI  - [Fluorescently labeled differentiating myelopeptide-4: specific binding to and
      penetration into target cells].
AB  - Myelopeptide-4 (MP-4) (Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro), inducing the terminal
      differentiation of HL-60 leukemia cells, was labeled with fluorescein
      isothiocyanate. The specific binding of this modified peptide to the surface of
      HL-60 cells and its ability to penetrate into the cells were studied. It was
      shown by cytometry and confocal microscopy to be bound on the HL-60 cell surface,
      to penetrate into their cytoplasm, and finally to concentrate around the cell
      nucleus. These phenomena are probably necessary for the exhibition of MP-4
      differentiating activity.

PMID- 17180908
TI  - [Rapid and efficient extraction of soluble proteins from gram-negative
      microorganisms without disruption of cell walls].
AB  - The ability of buffer solutions containing low concentrations of nonionic
      detergents (Triton X-100, Tween 20, Brij 58, and Lubrol PX) and the anionic
      detergent sodium deoxycholate, as well as mixtures of these detergents with
      chaeotropes (urea and guanidine hydrochloride), to extract intracellular proteins
      of Gram-negative microorganisms (Escherichia coli and Pseudomonas aeruginosa) was
      studied. It was established that the solutions containing Triton X-100 and sodium
      deoxycholate and the mixtures of these detergents with urea are the most
      effective. It was shown that the extraction of proteins from bacterial cells
      under the studied conditions is not accompanied by a release of DNA into solution
      but is associated with extraction of low-molecular RNAs. The level of protein
      extraction reaches 80%. No disruption of the bacterial cell wall occurs during
      the extraction, and proteins probably permeate through meshes of the murein
      network. The efficiencies of our buffer mixtures are close to or higher than that
      of the commercial reagent CelLytic B (Sigma, United States). The practical uses
      of the chaeotropic mixtures developed are discussed.

PMID- 17180909
TI  - [Residual dipolar couplings and molecular dynamic calculations as a source for
      refinement of protein spatial structures].
AB  - The precision of techniques and factors affecting the interpretation of residual
      dipolar couplings (RDCs) in analysis of spatial structures of partially aligned
      proteins are discussed. Experimental RDC values were obtained for pairs of 1H-15N
      nuclei of the protein barstar partially aligned in a liquid crystalline matrix of
      bicelles composed of dimiristoylphosphatidylcholine and
      dihexanoylphosphatidylcholine. The observed couplings agree well with the spatial
      structures of barstar determined earlier by X-ray and NMR methods. However, the
      differences between the experimental and calculated RDCs that were calculated on
      the basis of the known spatial structures of barstar, exceed the experimental
      errors three- to fourfold. These discrepancies can be explained by differences in
      the protein structures in solution and in crystal, a limited precision of the X
      ray analysis, and the intramolecular mobility of the protein molecule. A
      comparison of the results of modeling of the molecular dynamics of barstar in
      solution, crystal structures, and the experimental RDCs showed that the methods
      of molecular dynamics provide for a reasonable description of the character and
      amplitudes of internal motions and they should be considered for the correct
      determination of protein spatial structures from NMR spectroscopic data.

PMID- 17180911
TI  - [Retention of nucleic acid integrity in guanidine thiocyanate lysates of whole
      blood].
AB  - High-molecular-mass RNA and DNA have been shown to retain their integrity for
      three days at room temperature, no less than two weeks at +4 degrees C, and more
      than a year at -20 degrees C when whole blood samples are stored as lysates
      containing 4 M guanidine thiocyanate. Storage time at room temperature can be
      prolonged at least up to 14 days if nucleic acids were precipitated by two
      volumes of isopropanol. This preservation technique allows storage and
      transportation of samples at ambient temperature and is completely compatible
      with the procedure of subsequent isolation of nucleic acids.

PMID- 17180912
TI  - [Synthesis of heteroaromatic N-beta-glycosides of N-acetylglucosamine under the
      conditions of phase transfer catalysis: I. Glucosaminides of 2-oxobenzazoles].
AB  - Glycosylation of methylbenzoxazolone-2 and benzothiazolone-2 with the full
      acetate of alpha-D-glucosaminyl chloride in the phase transfer systems
      investigated (solid-organic solvent and aqueous alkali-organic solvent)
      regioselectively leads to the corresponding N-beta-D-glucosaminides, which is
      proved by 1H NMR spectroscopy and X-ray analysis.

PMID- 17180910
TI  - [New derivatives of alkyl- and aminocarbonylphosphonic acids containing 3'-azido
      3'-deoxythymidine].
AB  - New 5'-phosphonates of 3'-azido-3'-deoxythymidine were synthesized and shown to
      be low-toxic and markedly active in MT-4 cell cultures infected with HIV-1.

PMID- 17180913
TI  - [Structural characterization of tissue-specific galactan from flax fibers by 1H
      NMR and MALDI TOF mass spectrometry].
AB  - A high-molecular-mass polysaccharide galactan (M 2000 kDa) was isolated from flax
      at the stage of cell wall thickening of the bast fiber development. The polymer
      structure was studied by 1H NMR spectroscopy and MALDI TOF mass spectrometry. It
      is built up of Gal (59%), Rha (15%), GalA (23%), and Ara (3%) residues. The
      galactan backbone consists of successively alternating monomer disaccharide units
      (--> 4GalA1 --> 2Rha1 -->)n and is similar in its structure to the backbone of
      rhamnogalacturonan-1 (RG-I). Rhamnose residues bear in position 4 beta-(1 --> 4)
      galactose side chains of various lengths with a polymerization degree of up to 28
      or higher. A part of the side chains have branchings.

PMID- 17180914
TI  - [A uniform approach to the synthesis of carbohydrate conjugates of polyhedral
      boron compounds as potential agents for boron neutron capture therapy].
AB  - A uniform approach to the synthesis of carbohydrate conjugates with polyhedral
      boron compounds (PBCs) was developed. Oligosaccharide derivatives with an
      aglycone moiety amino group can be coupled with PBC carboxyl derivatives using N
      methyl-N-(4,6-dimethoxy-1,3,5-triazin-2-yl)morpholinium chloride as a coupling
      agent. Both N- and O-glycosides differing in the conformational mobility around
      the glycoside bond were shown to be useful as oligosaccharides with a functional
      group in the aglycone moiety. This allows the application of this approach to the
      synthesis of PBC conjugates with a wide range of oligosaccharides. For example,
      not only oligosaccharides obtained by chemical synthesis but also reducing
      oligosaccharides isolated from natural sources can be transformed into N
      glycosides. The approach was tested by the example of conjugation of the carboxyl
      derivatives of ortho-carborane and dodecaborate anion with lactose as a model
      oligosaccharide. Lactose, an easily available disaccharide, is a ligand for
      lectins expressed on the surface of melanoma cells. The approach suggested is the
      first example of the synthesis of such conjugates that does not require
      protective groups for the carbohydrate residue. It is especially important for
      obtaining dodecaborate-carbohydrate conjugates for which the removal of
      protective groups is often a non-trivial task.

PMID- 17180915
TI  - [Aminooxy analogues of spermine and their monoacetyl derivatives].
AB  - Convenient methods of synthesis of 1-aminooxy-3,8-diaza-11-aminoundecane, its
      earlier unknown N1-and N1 -acetyl derivatives, and also 1,10-bis(aminooxy)-3,8
      diazadecane are suggested. It is shown a possibility to selectively delete the
      acid-labile ethoxyethylidene protection of aminooxy group by hydrosulfates in the
      presence of N-tert-butyloxycarbonyl group.

PMID- 17180916
TI  - [Synthesis of (24S)-hydroxy- and (24S)-24,25-epoxycholesterol analogues,
      potential agonists of nuclear LXR receptors].
AB  - A new approach to the synthesis of a series of isomeric 24-hydroxy- and 24,25
      epoxysteroids starting from lithocholic acid was proposed. Sharpless asymmetric
      hydroxylation of intermediate delta24-olefines was used as a reaction determining
      the stereochemistry of target compounds. The resulting derivatives are potential
      agonists of nuclear receptors LXRalpha and LXRbeta and are potentially useful in
      the structure-function studies.

PMID- 17180917
TI  - [Synthesis and immunomodulating activity of new glycopeptides of glycyrrhizic
      acid containing residues of L-glutamic acid].
AB  - New glycopeptides of glycyrrhizic acid (GA) containing Glu residues and their
      alpha-methyl esters, gamma-methyl esters, and alpha,gamma-dimethyl esters were
      synthesized using N,N'-dicyclohexylcarbodiimide in the presence of N
      hydroxybenzotriazole or N-hydroxysuccinimide. Formation of amide bonds was
      observed on all the three COOH groups of GA, or selectively on the COOH groups of
      the GA carbohydrate part in dependence on the ratio of reagents and the reaction
      conditions. The GA glycopeptide with three residues of Glu(OH)-OMe at a dose of 2
      mg/kg stimulated the production of antibody-forming cells in mouse spleen in
      comparison with the control. The GA glycopeptide containing Glu residues only in
      the GA carbohydrate part turned out to be an immunosuppressor. The glycopeptide
      of the 30-methyl ester of GA with residues of free Glu in its carbohydrate part
      increased the hemagglutinine titer at oral doses of 2 and 10 mg/kg. All the
      studied compounds had practically no effect on the delayed-type hypersensitivity
      in mice.

PMID- 17180918
TI  - [Regulation of metabolic and energetic mitochondrial functions by hormones and
      signal transduction systems].
AB  - The discovery of the complex regulation of mitochondria functions by hormones and
      signal transduction systems is one of the new and important achivements of
      mitochondriology. A number of hormones of all the chemical classes and with
      different action mechanisms stimulate many mitochondrial processes, including
      Krebs cycle, respiratory chain, oxidative phosphorylation, energy dependent
      syntheses. These effects are realized and/or reproduced by receptors, the second
      messengers (cAMP, Ca2+, diacylglycerol), protein and tyrosine kinases, anchor
      proteins, transcription factors. All the main kinases are found in mitochondria;
      protein kinases and/or tyrosine kinases phosphorylate the protein 18 kDa from
      complex I, cytochrome c-oxidase, ATP-synthase, protein binding to cAMP/Ca2+
      response element, voltage dependent anione channel, steroidogenic acute protein,
      proapoptotic protein BAD and also other proteins of mitochondrial membranes.
      Pleiotropy of calcium regulation of mitochondrial functions is proved. The
      receptors of lipophilic hormone, growth hormone, epidermal growth factor and
      neurotrophins are discovered in mitochondria. In cellular signaling mitochondria
      play the integrative role.

PMID- 17180919
TI  - [Study of conformational homology for the HIV-1 gpi20 V3 loop. structural
      analysis of the HIV-RF and HIV-Thailand viral strains].
AB  - A conformation of the H-IV-RF gp120 V3 loop giving rise to the virus principal
      neutralizing determinant as well as determinants of cell tropism and syncytium
      formation was built by computer modeling methods using NMR spectroscopy data. The
      elements of the HIV-RF V3 loop secondary structure and conformational states of
      its irregular stretches were determined. The structural elements preserved in two
      viral strains, were identified using the comparative analysis of simulated
      structure with that of homologous site for the HIV-Thailand gp120 V3 loop.
      Conservative structure elements of the HIV-1 V3 loop are considered to be
      promising targets for deriving its chemically modified forms characterized by the
      enhanced immunogenicity and cross-reactivity of neutralizing antibodies, as well
      as for the antiviral drug design resulting from these researches.

PMID- 17180921
TI  - [Hypoclorous acid modifies rat liver and heart enzymes of the pentose phosphate
      pathway and antioxidative defence in vitro].
AB  - Hypoclorous acid is an effective biological oxidant produced by activated
      neutrophils. HOCl plays a role of the major inflammation mediator in mammalian
      tissues. The aim of the present study was to investigate the mechanisms of
      hypochlorous acid-induced modification of antioxidant enzymes, which defence the
      cell under oxidative stress, and enzymes of the pentose phosphate pathway, which
      supply reducing equivalents in the cell. HOCl (100-1000 microM) in vitro
      inhibited considerably in a dose-dependent manner the activity of the enzymes of
      the pentose phosphate pathway in the rat liver postmitochondrial fraction. HOCI
      at a concentration of 100 nmol/mg protein inhibited transketolase activity by 65
      +/- 5%, glucose-6-phosphate dehydrogenase--by 50 +/- 5% and 6-phosphogluconate
      dehydrogenase--by 55 +/- 5%. The activities of glutathione peroxidase and
      catalase slightly decreased. On the contrary, in the rat heart postmitochondrial
      fraction HOCl (100-1000 microM) inhibited considerably catalase, increased
      glutathione peroxidase activity and decreased significantly the activity of the
      key enzymes of the pentose phosphate pathway. The inhibition of the pentose
      phosphate pathway enzymes was accompanied by oxidation of intracellular reduced
      glutathione, oxidative protein modification (protein carbonyl group accumulation,
      mixed protein-glutathione disulphides and chloramine formation), and membrane
      lipid peroxidation. The sensitivity of rat heart cell components to oxidative
      damage by HOCl was higher in comparison with that of the liver.

PMID- 17180920
TI  - [Nanoelectrochemistry of cytochrome P450s: direct electron transfer and
      electrocatalysis].
AB  - The present study demonstrates the direct electron transfer between cytochrome
      P450 2B4 (CYP2B4), P450 1A2 (CYP1A2), sterol 14alpha-demethylase (CYP51MT) and
      screen printed graphite electrodes, modified with gold nanoparticles and
      didodecyldimethylammonium bromide (DDAB). Electrodetection of heme proteins is
      possible when 2-200 pmol P450/electrode were adsorbed on the surface of
      nanostructured electrochemical interfaces. Electron transfer, direct
      electrochemical reduction and interaction with P450 substrates (oxygen,
      benzphetamine, lanosterol) and inhibitor ketoconazole were analyzed using cyclic
      voltammetry (CV), square wave (SWV) or differential pulse (DPV) voltammetry,
      amperometry.

PMID- 17180922
TI  - [Catalytic properties of 6-phosphogluconate dehydrogenase from rat liver in
      normal state and during toxic hepatitis].
AB  - Experimental toxic hepatitis is accompanied by a decrease of 6-phosphogluconate
      dehydrogenase (6PGD, 1.1.1.44) activity in rat liver. Enzyme preparations of
      6PGD, obtained from livers of control group rats and animals with toxic exhibit
      the same molecular mass of 114.2 +/- 5.8 kDa. However G6PD isolated from liver of
      animals with toxic hepatitis exhibited altered Km and pH-optimum values. Reduced
      glutathione inhibited 6PGD-activity from the liver of control group rats and did
      not affect the enzyme from liver of animals with toxic hepatitis. Inhibition
      effect of oxidized glutathione is stronger in the pathological state. Malate,
      citrate, 2-oxoglutarate and isocitrate activated the enzyme from control animals,
      but did not the enzyme isolated from animals with hepatitis. Regulation of 6PGD
      activity from liver of control and experimental animals by some nucleotides (NAD,
      ADP, AMP) and ribose-5-phosphate was also different.

PMID- 17180923
TI  - [Interrupted alcohol treatment and liver: free radical homeostasis, nitric oxide,
      adaptive mechanisms].
AB  - Alcohol administration can result in liver damage. Reactive oxygen species (ROS),
      nitric oxide (NO) and their interaction are crucial factors in this process. The
      aim of work was to investigate, free radical state and mechanisms of adaptation
      of the antioxidant system (AOS) to stress, caused by interrupted alcohol intake.
      Repeated cycles of alcoholization caused an imbalance between production and
      utilization of various ROS. This imbalance was due to impairments in the system
      superoxide dismutase/catalase. Nevertheless, in most experimental groups there
      was clear reduction of lipid peroxidation (LPO) products evaluated by
      thiobarbituric acid reactive substances. This might be attributed to the
      antioxidant effect of NO. However, there was an increased level of transaminases
      in blood plasma. After 28 days of this experimental scheme all the parameters
      studied normalized.

PMID- 17180924
TI  - [A short test for potential carcinogenicity of water soluble synthetic polymers].
AB  - The effect of synthetic water-soluble polymer with different structure on the
      appearance in SZNA mice of carcinogen-protein adducts (CPA) containing endogenous
      carcinogen, 3-oxyanthranilic acid (3-OAA), was investigated. CPA containing 3-OAA
      (3-OAA-CPA) were detected during the administration of 24 of 30 investigated
      polymers. The induction of 3-OAA-CPA and the character of their distribution in
      the organism (in all investigated tissues: serum, extracts of liver, spleen,
      lungs and kidneys tissues or in single tissues) depended on the chemical
      structure of polymers. It is concluded, that synthetic polymers represent
      potential cancerogenic danger, because their administration causes formation of 3
      OAA-CPA in the organism of animals.

PMID- 17180925
TI  - [Bioluminescent method for determination of concentration metabolic substrates
      and NAD+ in the lymphocytes].
AB  - We have developed a new bioluminescent method for determination of concentrations
      of pyruvate, lactate, malate, glutamate and NAD+ in the periferal blood
      lymphocytes from mice with Ehrlich ascites carcinoma. There were blood samples of
      intact mice for control. We found that variations of these substrates, depend on
      stage of malignant growth.

PMID- 17180926
TI  - [Suppression of 5-lipoxygenase activity by anionic cholesterol derivatives].
AB  - 5-Lipoxygenase (5-LO) is a key enzyme involved in leukotriene (LTs) biosynthesis
      which act as host defense mediators, and inflammatory agents as well. In this
      work the influence of anionic cholesterol derivatives on 5-LO activity has been
      investigated. Cholesterol sulfate activated human polymorphonuclear leukocytes
      (PMNL) and stimulated their adhesion to endothelium and collagen. Cholesterol
      sulfate and cholesterol phosphate suppressed leukotriene production in PMNL and
      in rat RBL-1 cells. Kinetic characteristics of this process are presented.
      Cholesterol phosphate (charge -2) was shown to be more potent inhibitor then
      cholesterol sulfate (charge-1) in all experiments. We suppose that this fact
      highlights the importance of negatively charged ester groups to suppress 5-LO
      activity.

PMID- 17180928
TI  - [Depressive disorders in general medical practice].

PMID- 17180927
TI  - [The non-functioning chaperonin GroEL stimulates protein aggregation].
AB  - To clarify the role of chaperones in the development of amyloid diseases, the
      interaction of the chaperonin GroEL with misfolded proteins and recombinant
      prions has been studied. The efficiency of the chaperonin-assisted folding of
      denatured glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was shown to decrease
      in the presence of prions. Prions are capable of binding to GroEL immobilized on
      Sepharose, but this does not prevent the interaction between GroEL and other
      denatured proteins. The sizes of individual proteins (GroEL, GAPDH, and the
      recombinant prion), as well as aggregates formed after their mixing, were
      determined by the dynamic light scattering method. It was shown that at 25
      degrees C the non-functioning chaperonin (equimolar mixture of GroEL and GroES in
      the absence of Mg-ATP) bound prion yielding large aggregates (greater than 400
      nm). The addition of Mg-ATP decreased significantly the aggregate size to 70-80
      nm. On the blocking of one of the chaperonin centers by oxidized denatured GAPDH,
      the aggregate size increased to 1200 nm, and the addition of Mg-ATP did not
      prevent the aggregation. These data indicate the significant role of chaperonins
      in the formation of amyloid structures and demonstrate the acceleration of
      aggregation in the presence of functionally inactive chaperonins. The suggested
      model can be used for the analysis of the efficiency of antiaggregants in the
      system containing chaperonins.

PMID- 17180929
TI  - [Platelet activation and inflammation markers in patients with coronary heart
      disease and depression].
AB  - AIM: To study morphological features and functional activity of platelets, their
      relations with the level of inflammation markers in coronary heart disease (CHD)
      patients with depression. MATERIAL AND METHODS: The study group consisted of 33
      CHD patients with stable effort angina (NY-HA FC I-III), 14 had depression, 19
      were free of depression. Sixteen healthy volunteers comprised the control group.
      Platelet aggregation was registered by a mean size of aggregates and
      turbidometrically. Platelets shape, leukocytic-thrombocytic and erythrocytic
      thrombocytic aggregates (LTA, ETA) in the whole blood were studied electron
      microscopically. The levels of IL-2, IL-6, TNF-alpha, sVCAM, hsCRP were measured
      in the blood, serotonin--in platelets. RESULTS: Spontaneous aggregation enhanced
      in 52.6% CHD patients (p < 0.05). The blood contained reticular platelets, high
      number of prothrombocytes (p < 0.05), mean volume of thrombocytes was greater (p
      < 0.05). This reflected changes in megakaryocytopoiesis. Some of the patients had
      LTA and ETA. Out of inflammation markers, only IL-6 and sVCAM were elevated (p <
      0.01), hsCRP concentration rose, but not above normal range. Serotonin in
      platelets was the same in the patients and controls. Depression aggravated the
      disorders and elevated other indices. Spontaneous aggregation was high in 71.4%
      of depressive CHD patients. The count of reticular platelets, prothrombocytes,
      mean volume platelets were also elevated. LTA and ETA were high in all the
      depressive patients. Elevated were also concentrations of IL-6, sVCAM, IL-2,
      hsCRP. Serotonin in platelets was low (p < 0.05). CONCLUSION: Depression
      stimulates functional activity of platelets, is a factor of risk of intravascular
      inflammation and contributes to development of thrombotic complications in CHD
      patients.

PMID- 17180930
TI  - [Acute disorders of cerebral circulation: prognostic factors in essential
      hypertension].
AB  - AIM: To study subclinical signs of cerebrovascular pathology as prognostic
      factors of development of acute disorders of cerebral circulation (ADCC) in
      essential hypertension (EH). MATERIAL AND METHODS: A prospective (10-13 years)
      cohort trial of prognostic significance of subclinical forms of cerebral
      pathology in EH in relation to ADCC development covered 111 men aged 45-55 years
      who had undergone a unified neurological and cardiological examination in 1992
      1993. RESULTS: Such factors as disordered circulation along major arteries of the
      head (a relative risk 3.1 [1.2; 10.3]), thick intima-media complex of the common
      carotid artery (a relative risk: 5.2 [2.1; 14.3]), the presence of asymptomatic
      lacunar brain infarctions (a relative risk: 6.6 [2.3; 13.5]) were revealed to be
      of unfavourable prognostic significance in respect to development of ADCC in EH.
      CONCLUSION: Some subclinical risk factors may have prognostic value in relation
      to development of ADCC in EH.

PMID- 17180933
TI  - [Damage to the kidneys in diabetes mellitus type 2].

PMID- 17180932
TI  - [Stroke and diabetes mellitus type 2. Possibilities of prevention].

PMID- 17180931
TI  - [Infarction-like changes on electrocardiogram in acute disorder of cerebral
      circulation].

PMID- 17180934
TI  - [Multicomponent approach to treatment of diabetes mellitus and its complications
      (lecture)].

PMID- 17180936
TI  - [Use of proteasome inhibitors in the treatment of patients with multiple
      myeloma].

PMID- 17180935
TI  - [Current options of insulin resistence correction in patients with metabolic
      syndrome].
AB  - AIM: To study thiasolidindion drug pioglitazone for efficacy in metabolic
      syndrome (MS). MATERIAL AND METHODS: Twenty patients with MS were examined at
      baseline and after 12 week therapy with pioglitazone. The examination included
      estimation of fasting and postprandial glycemia, insulin resistance index, HOMA
      IR index, HbAlc, lipid profile, microalbuminuria (MAU), blood pressure,
      endothelium-related vasodilation. RESULTS: Pioglitazone therapy for 12 weeks
      significantly reduced HbAlc, fasting and postprandial glycemia, insulinemia, HOMA
      IR, improved blood lipid spectrum, reduced visceral obesity. CONCLUSION: Positive
      effects were also achieved on blood pressure, MAU and endothelium-related
      vasodilation.

PMID- 17180937
TI  - [The modified program NHL-BFM-90 in the treatment of patients with diffuse large
      B-cell lymphosarcoma].
AB  - AIM: To investigate efficacy of the modified protocol NHL-BFM-90 in patients with
      diffuse large B-cell lymphosarcoma (DLBCLS). MATERIAL AND METHODS: A total of 13
      DLBCLS patients with stage II-IV of the disease with affection of lymph nodes at
      the disease onset (nodal lesion) and stage II with tumor size more than 10 cm
      (bulky disease) received first-line treatment according to the modified program
      NHL-BFM-90 from 2002 to 2005. The diagnosis was made by WHO criteria. RESULTS: A
      complete remission was achieved in 76.9% patients. Resistance to therapy was
      observed in the patients with bone marrow affection. The 2.5-year overall
      survival was 74%, 2-year event-free survival was 75% (the events were recurrence
      and resistance). Follow-up continued from 5 to 47 months. CONCLUSION: The
      efficacy of the modified protocol NHL-BFM-90 in DLBCLS patients with stage III-IV
      of the "nodal" disease and stage II of the "bulky" disease was high.

PMID- 17180938
TI  - [Allogeneic transplantation of the kidney in a patient with B-small cell
      lymphocytic lymphoma and chronic renal failure].

PMID- 17180939
TI  - [Diagnosis of arteriogenic erectile dysfunction at the level of primary health
      care].
AB  - AIM: To study relations between endothelial function of the brachial and
      cavernous arteries (BA and CA). MATERIAL AND METHODS: The trial was made in 148
      males with erectile dysfunction (ED) aged 21 to 80 years (a mean age 52.6 years)
      and 40 males aged 24 to 76 years (a mean age 50.2 years) with normal erection
      (the control group). A pathogenetic form of ED was determined in each patient. CA
      endothelium function was estimated in the patients and controls by an original
      technique of ultrasonic investigation of postcompression changes in CA diameter.
      Such changes were also estimated for BA diameter. RESULTS: The correlation
      analysis of BA and CA endothelial function has not found significant correlations
      between BA and CA endothelial functions both in the groups and in all the
      examinees. Prevalence of systemic endothelial dysfunction in the controls and
      patients with psychogenic, neurogenic and vein-occusive ED was maximum 30% while
      in arteriogenic ED endothelial dysfunction was discovered in all the examinees.
      CONCLUSION: In diagnosis of arteriogenic ED the study of BA endothelial function
      can not adequately replace such of CA, but the presence of BA endothelial
      dysfunction may be associated with CA endothelial dysfunction.

PMID- 17180940
TI  - [Nebivolol effects on the cardiovascular system and the kidneys in pregnant and
      puerperal women with hypertension].
AB  - AIM: To study nebivolol efficacy in pregnant and puerperal women with
      hypertension. MATERIAL AND METHODS: Monitoring of endothelial function, central
      and peripheral hemodynamics (HD), myocardial function, intrarenal circulation and
      microalbuminuria (MAU) was performed in 90 pregnant (67 hypertensive and 23
      normotensive) and 18 puerperal women who were diagnosed to have hypertension in
      pregnancy. The above parameters were estimated in 23 hypertensive gravidas and 18
      puerperas treated with nebivolol. RESULTS: Hypertensive gravidas had marked
      endothelial dysfunction (ED), impaired intrarenal HD, MAU, high total peripheral
      vascular resistance and left ventricular myocardial mass index (LVMMI). The
      puerperas with hypertension had ED, MAU, frequently HD disorders and a trend to a
      LVMMI rise. Nebivolol effectively reduced blood pressure, had a nephroprotective
      action, and improved HD and endothelial function. CONCLUSION: Nebivolol (a highly
      selective beta 1-adrenoblocker) administration is effective pathogenetic
      treatment of pregnant and puerperal women with hypertension and may improve short
      and long-term prognoses of such patients.

PMID- 17180941
TI  - [Acute urate nephropathy in perimenopausal women].

PMID- 17180942
TI  - [Clinical, vegetative and cognitive disorders in hypertensive postmenopausal
      women in relation to menopause causes].
AB  - AIM: To specify clinical, vegetative and cognitive disorders in hypertensive
      women depending on the type of menopause. MATERIAL AND METHODS: A total of 195
      hypertensive women were divided into three groups: group 1 (n = 50, age 45.6 +/-
      4.5 years) consisted of premenopausal women, group 2 (n = 100, age 57.4 +/- 4.7
      years) - of women with natural menopause, group 3 (n = 45, age 55.1 +/- 5.9
      years)--with early and/or surgical menopause. Severity of the menopausal
      syndrome, anxiety, depression, alexitimia, mental performance, vegetative
      regulation of heart rhythm were examined. RESULTS: The premenopausal women were
      characterized by cardial and cerebral disorders, unaffected psychovegetative
      function and initial symptoms of lowering mental performance. Hypertensive women
      with natural menopause showed combination of cardial and cerebral symptoms with
      moderate anxio-depressive disorders, alexitimia, subnormal parasympathetic
      activity of the autonomic nervous system in high centralization of heart rhythm
      regulation and attention disturbances. Patients with surgical and/or early
      menopause had marked cardial and cerebral symptoms, moderate anxiodepressive
      disorders, alexitimia, inhibition of mental performance, vegetative dysfunction,
      overcentralization of heart rhythm control. CONCLUSION: With development of
      postmenopausal metabolic symptom complex, severity of hypertension grows with
      emergence of anxiodepressive disorders which combine with vegetative regulation
      disorders and attenuation of mental performance.

PMID- 17180943
TI  - [Chronic myeloproliferative diseases and pregnancy].
AB  - AIM: To analyse the course of pregnancy in chronic myeloproliferative diseases
      (CMPD) with hyperthrombocytosis, primarily, essential thrombocytemia. MATERIAL
      AND METHODS: The analysis of thrombogenic risk factors covered literature data
      and 8 cases observed by the authors. RESULTS: Six pregnant women received long
      term treatment with preparations of interferon-alpha in a dose 9-20 million IU a
      week (both before and during pregnancy). Rapid reduction of hyperthrombocytosis
      (1100-4000 x 10(9) l) and the absence of a negative effect on development of the
      fetus were seen in all the cases. Normal delivery on week 37-39 was in 4
      patients, spontaneous abortion on week 24 was provoked by a car accident. Three
      gravidas (gestational week 28, 33 and 34) are still under observation. Lupus
      anticoagulant or elevation of anticardiolipin antibodies level was detected in 4
      of 8 patients, 2 patients had heterozygous mutation of
      methylentetrahydrofolatereductase genes and factor V (Leiden). These patients
      were given lannacher, faxiparine, folic acid and discrete plasmapheresis (in 2
      cases). CONCLUSION: Gravidas with hyperthrombocytosis, if not contraindicated,
      must be treated with aspirin and interferon-alpha preparations at any gestational
      term. Moreover, it is necessary to exclude additional most prevalent causes of
      thrombophilia for adequate prevention of thromboses.

PMID- 17180944
TI  - [Biochemical markers of bone formation in hemodialysis and after
      allotransplantation of cadaveric kidney].
AB  - AIM: To ascertain informative value of estimation of bone forming markers in
      patients on chronic hemodyalisis (CHD) and recipients of cadaveric kidney (CK).
      MATERIAL AND METHODS: Parathyroid hormone (PTH), beta-crosslaps (CTX),
      osteocalcin (OC), amino-terminal procollagen propeptide 1 (PINP), bone alkaline
      phosphatase (BAP), bone mineral density (BMD) were determined in 152 patients on
      CHD (89 males and 63 females aged 49 +/- 13 years) and 195 CK recipients (106
      males and 89 females aged 42 +/- 12 years) 30 +/- 38 months after kidney
      transplantation. RESULTS: PTH, CTX and BAP determination specifies skeletal
      disease (secondary hyperparathyroidism or adynamic bone disease) in CHD patients.
      In patients with CK recipients osteoporosis differed from osteopenia by higher
      levels of PTH, CTX, OC in the absence of any differences in BAP, PINP. All bone
      forming markers were lower than CTX showing suppression of bone forming. Bone
      fractures in CK recipients' anamnesis were associated with OC and BAP decrease in
      men and low border of normal OC in women. Determination of bone formation and
      resorption markers in patients on CHD and CK recipients is of great clinical
      importance.

PMID- 17180945
TI  - [Implanted cardioverters-defibrillators in the treatment of arrhythmias and
      prevention of sudden death].
AB  - AIM: To present 15-year experience in use of implantable cardioverters
      defibrillators (ICD) in patients with life threatening arrhythmias and a high
      risk of sudden cardiac death (SCD). MATERIAL AND METHODS: A total of 151 patients
      (116 males and 35 females aged 12-75 years) with life threatening arrhythmias and
      ICD were studied. RESULTS: There were neither complications nor lethality.
      Electrocardiotherapy was performed in 89 (58.9%) patients 4.5 +/- 9.4 months, on
      the average, after ICD implantation. Attacks of ventricular tachycardia (VT) were
      arrested by antitachycardia stimulation (974 episodes, 37.5 +/- 92.5 per patient,
      on the average). Effective cardioversion in VT was observed in 63 (41.7%) cases.
      Episodes of rapid ventricular tachycardia and ventricular fibrillation were
      stopped by defibrillation shocks in 28 (18.5%) patients. Additional surgical
      interventions were made in 3 patients because of electrodes dislocation, in 1-
      because of electrode brakage and in 1--suppuration of the bed. Fifteen patients
      (9%) died during follow-up because of cardiac failure (n = 13), cancer (n = 1),
      unknown cause (n = 1). CONCLUSION: Clinical application of ICD is not only
      treatment of arrhythmia and prevention of SCD but it is also a method of
      diagnosis, collection and accumulation of information about the disease course.

PMID- 17180946
TI  - [Atherosclerosis and osteoporosis: common views on the problem].

PMID- 17180947
TI  - [Current knowledge about the role of infection in genesis of atherosclerosis].

PMID- 17180948
TI  - [Low back pain and its treatment].

PMID- 17180949
TI  - What is "emerging"?

PMID- 17180950
TI  - Perfluorinated surfactants contaminate German waters.

PMID- 17180951
TI  - What lurks in cooling towers?

PMID- 17180952
TI  - Composting industrial waste.

PMID- 17180953
TI  - Barbiturates' environmental legacy.

PMID- 17180954
TI  - Emerging DBPs in drinking water.

PMID- 17180955
TI  - PBDEs in Great Lakes fish.

PMID- 17180956
TI  - A European union of analytical labs.

PMID- 17180957
TI  - REACH--the new European chemicals law.

PMID- 17180958
TI  - Campylobacter in waterfowl and aquatic environments: incidence and methods of
      detection.
AB  - Campylobacters are emerging as one of the most significant causes of human
      infections worldwide, and the role that waterfowl and the aquatic environment
      have in the spread of disease is beginning to be elucidated. On a world scale
      campylobacters are possibly the major cause of gastrointestinal infections.
      Campylobacters are common commensals in the intestinal tract of many species of
      wild birds, including waterfowl. They are also widely distributed in aquatic
      environments where their origins may include waterfowl as well as sewage
      effluents and agricultural runoff. Campylobacters have marked seasonal trends. In
      temperate aquatic environments they peak during winter, whereas spring-summer is
      the peak period for human infection. Campylobacter species may survive, and
      remain potentially pathogenic, for long periods in aquatic environments. The
      utility of bacterial fecal indicators in predicting the presence of
      campylobacters in natural waters is questionable. Viable but nonculturable
      Campylobacter cells may occur, but whether they have any role in the generation
      of outbreaks of campylobacteriosis is unclear. The routine detection of
      Campylobacter spp. in avian feces and environmental waters largely relies on
      conventional culture methods, while the recognition of a particular species or
      strain is based on serotyping and increasingly on molecular methods. Thus, PCR
      combined with selective enrichment enhances the detection of campylobacters in
      water and feces, while DNA sequencing facilitates recognition of particular
      species and strains.

PMID- 17180959
TI  - Human adenoviruses in water: occurrence and health implications: a critical
      review.
AB  - Adenoviruses are important human pathogens that are responsible for both enteric
      illnesses and respiratory and eye infections. Recently, these viruses have been
      found to be prevalent in rivers, coastal waters, swimming pool waters, and
      drinking water supplies worldwide. United Sates Environmental Protection Agency
      (USEPA) listed adenovirus as one of nine microorganisms on the Contamination
      Candidate List for drinking water because their survival characteristic during
      water treatment is not yet fully understood. Adenoviruses have been found to be
      significantly more stable than fecal indicator bacteria and other enteric viruses
      during UV treatment. Adenovirus infection may be caused by consumption of
      contaminated water or inhalation of aerosolized droplets during water recreation.
      The goal of this review is to summarize the state of technology for adenovirus
      detection in natural and drinking waters and the human health risk imposed by
      this emerging pathogen. The occurrence of these viruses in natural and treated
      waters is summarized from worldwide reports.

PMID- 17180960
TI  - Occurrence of Escherichia coli O157:H7 and other enterohemorrhagic Escherichia
      coli in the environment.
AB  - Enterohemorrhagic Escherichia coli (EHEC) (O157 and other serotypes) are zoonotic
      pathogens linked with severe human illnesses. The main virulence factors of EHEC
      are the Shiga toxins, among others. Most of the genes coding for these toxins are
      bacteriophage-encoded. Although ruminants are recognized as their main natural
      reservoir, water has also been documented as a way of transmission of EHEC. E.
      coli O157:H7 and other EHEC may contaminate waters (recreational, drinking or
      irrigation waters) through feces from humans and other animals. Indeed, the
      occurrence of EHEC carrying the stx2 gene in raw municipal sewage and animal
      wastewater from several origins has been widely documented. However, the
      evaluation of the persistence of naturally occurring EHEC in the environment is
      still difficult due to methodological problems. Methods proposed for the
      detection and isolation of stx-encoding bacteria, ranging from the classic
      culture-based methods to molecular approaches, and their application in the
      environment, are discussed here. Most virulence factors associated with these
      strains are linked to either plasmids or phages, and consequently they are likely
      to be subject to horizontal gene transfer between species or serotypes. Moreover,
      the presence of infectious stx-phages isolated as free particles in the
      environment and their high persistence in water systems suggest that they may
      contribute to the spread of stx genes, as they are directly involved in the
      emergence of new pathogenic strains, which might have important health
      consequences.

PMID- 17180961
TI  - Environment arrays: a possible approach for predicting changes in waterborne
      bacterial disease potential.
AB  - Current molecular techniques for identifying bacteria in water have proven
      useful, but they are not reliably predictive of impending disease outbreaks.
      Genomics-based approaches will help to detect the presence of pathogens quickly
      and well before they grow into a population that poses a risk to public health.
      We suggest that genomics is only one component of the toolbox that will be needed
      to identify emerging waterborne threats. We propose a methodology beyond
      genomics, based on activity in the mobile genome. This approach makes use of a
      new device called an environment array. The array will depend upon the same
      research necessary for genomics-based detection, but will not require an a priori
      knowledge of virulence genes. Environment arrays are assembled from molecular
      profiles of the infectious elements that transfer between bacteria. The advantage
      of the array is that it monitors the activity of the mobile genome, rather than
      the presence of particular DNA sequences. Environmental arrays should thus be
      many times more sensitive than traditional hybridization or PCR-based techniques
      that target already-known DNA sequences. Mobile elements are known to respond to
      new environmental conditions that may correlate with a chemical contamination or
      the bloom of bacterial pathogens, potentially allowing for a much broader
      application in detecting unknown or unanticipated biological and chemical
      contaminants.

PMID- 17180962
TI  - Are there other persistent organic pollutants? A challenge for environmental
      chemists.
AB  - The past 5 years have seen some major successes in terms of global measurement
      and regulation of persistent, bioaccumulative, and toxic (PB&T) chemicals and
      persistent organic pollutants (POPs). The Stockholm Convention, a global
      agreement on POPs, came into force in 2004. There has been a major expansion of
      measurements and risk assessments of new chemical contaminants in the global
      environment, particularly brominated diphenyl ethers and perfluorinated alkyl
      acids. However, the list of chemicals measured represents only a small fraction
      of the approximately 30,000 chemicals widely used in commerce (>1 t/y). The vast
      majority of existing and new chemical substances in commerce are not monitored in
      environmental media. Assessment and screening of thousands of existing chemicals
      in commerce in the United States, Europe, and Canada have yielded lists of
      potentially persistent and bioaccumulative chemicals. Here we review recent
      screening and categorization studies of chemicals in commerce and address the
      question of whether there is now sufficient information to permit a broader array
      of chemicals to be determined in environmental matrices. For example, Environment
      Canada's recent categorization of the Domestic (existing) Substances list, using
      a wide array of quantitative structure activity relationships for PB&T
      characteristics, has identified about 5.5% of 11,317 substances as meeting P & B
      criteria. Using data from the Environment Canada categorization, we have listed,
      for discussion purposes, 30 chemicals with high predicted bioconcentration and
      low rate of biodegradation and 28 with long range atmospheric transport potential
      based on predicted atmospheric oxidation half-lives >2 days and log air-water
      partition coefficients > or =5 and < or =1. These chemicals are a diverse group
      including halogenated organics, cyclic siloxanes, and substituted aromatics. Some
      of these chemicals and their transformation products may be candidates for future
      environmental monitoring. However, to improve these predictions data on emissions
      from end use are needed to refine environmental fate predictions, and analytical
      methods may need to be developed.

PMID- 17180963
TI  - Poly and perfluorinated carboxylates in North American precipitation.
AB  - Although perfluorocarboxylates (PFCAs) have been detected in a number of
      environmental matrices, there are very few reports on concentrations in
      precipitation. In this study PFCAs, fluorotelomercarboxylates (FTCAs), and
      fluorotelomer-unsaturated carboxylates (FTUCAs), were determined in wet only
      precipitation samples from nine sites in North America. The analytical method
      involved derivatization of the carboxylates and measurement of the 2,4
      difluoroanilide by GC-MS. Samples from three remote sites in Canada had low
      concentrations of perfluorooctanoate (PFOA) (<0.1-6.1 ng/L). Significantly higher
      concentrations of PFOA were found at 4 northeastern United States and 2 southern
      urban Canadian sites, with Delaware having the highest levels (85 ng/L PFOA, with
      a range of 0.6-89 ng/L) and a maximum flux of 13 000 ng/m2. 8:2- and 10:2 FTCAs
      and FTUCAs were detected at all 4 U.S. sites and 2 urban Canadian sites (<0.07
      8.6 ng/L), most frequently at the Delaware site. Longer chained PFCAs (deca-,
      undeca-, and dodeca-perfluorocarboxylates) were detected (<0.07-5.2 ng/L) at 2
      urban Ontario sites but not determined in other samples. Air mass back trajectory
      results for 3 U.S. sites indicate highly populated urban areas in the New York to
      Washington corridor as the main sources of PFOA, although low PFOA levels
      associated with air masses coming off the Atlantic Ocean imply multiple sources.

PMID- 17180964
TI  - Occurrence of a new generation of disinfection byproducts.
AB  - A survey of disinfection byproduct (DBP) occurrence in the United States was
      conducted at 12 drinking water treatment plants. In addition to currently
      regulated DBPs, more than 50 DBPs that rated a high priority for potential
      toxicity were studied. These priority DBPs included iodinated trihalomethanes
      (THMs), other halomethanes, a nonregulated haloacid, haloacetonitriles,
      haloketones, halonitromethanes, haloaldehydes, halogenated furanones, haloamides,
      and nonhalogenated carbonyls. The purpose of this study was to obtain
      quantitative occurrence information for new DBPs (beyond those currently
      regulated and/or studied) for prioritizing future health effects studies. An
      effort was made to select plants treating water that was high in total organic
      carbon and/or bromide to enable the detection of priority DBPs that contained
      bromine and/or iodine. THMs and haloacetic acids (HAAs) represented the two major
      classes of halogenated DBPs formed on a weight basis. Haloacetaldehydes
      represented the third major class formed in many of the waters. In addition to
      obtaining quantitative occurrence data, important new information was discovered
      or confirmed at full-scale plants on the formation and control of DBPs with
      alternative disinfectants to chlorine. Although the use of alternative
      disinfectants (ozone, chlorine dioxide, and chloramines) minimized the formation
      of the four regulated THMs, trihalogenated HAAs, and total organic halogen (TOX),
      several priority DBPs were formed at higher levels with the alternative
      disinfectants as compared with chlorine. For example, the highest levels of
      iodinated THMs-which are not part of the four regulated THMs-were found at a
      plant that used chloramination with no prechlorination. The highest concentration
      of dichloroacetaldehyde was at a plant that used chloramines and ozone; however,
      this disinfection scheme reduced the formation of trichloroacetaldehyde.
      Preozonation was found to increase the formation of trihalonitromethanes. In
      addition to the chlorinated furanones that have been measured previously,
      brominated furanones-which have seldom been analyzed-were detected, especially in
      high-bromide waters. The presence of bromide resulted in a shift to the formation
      of other bromine-containing DBPs not normally measured (e.g., brominated ketones,
      acetaldehydes, nitromethanes, acetamides). Collectively, -30 and 39% of the TOX
      and total organic bromine, respectively, were accounted for (on a median basis)
      bythe sum of the measured halogenated DBPs. In addition, 28 new, previously
      unidentified DBPs were detected. These included brominated and iodinated
      haloacids, a brominated ketone, and chlorinated and iodinated aldehydes.

PMID- 17180965
TI  - Benzotriazole and tolyltriazole as aquatic contaminants. 1. Input and occurrence
      in rivers and lakes.
AB  - The complexing agents benzotriazole (BT) and tolyltriazole (TT) are not only
      widely applied as anticorrosives, e.g., in aircraft deicer and anti-icer fluid
      (ADAF), but they are also used for so-called silver protection in dishwasher
      detergents. Due to their low biodegradability and limited sorption tendency, BT
      and TT are only partly removed in wastewater treatment. Residual concentrations
      of BT and TT were determined in ambient surface waters in Switzerland including 7
      rivers which have distinct water flows and receive treated wastewater effluents
      at various dilution ratios. A maximum BT concentration of 6.3 microg/L was found
      in the Glatt River, and a maximum mass flow of 277 kg BT per week was observed in
      the Rhine River. In most cases, TT was about a factor 5-10 less abundant. During
      winter 2003/4, BT mass flows at 2 locations in the lower stretch of the Glatt
      River clearly indicated the input from nearby Zurich airport, where BT was
      applied as an anticorrosive ADAF component. BT concentrations measured in the
      three lakes Greifensee, Lake Zurich, and Lake Geneva were approximately 1.2, 0.1
      0.4, and 0.2 microg/L, respectively. The observed environmental occurrences
      indicate that BT and TT are ubiquitous contaminants in the aquatic environment
      and that they belong to the most abundant individual water pollutants.

PMID- 17180966
TI  - Discharge of three benzotriazole corrosion inhibitors with municipal wastewater
      and improvements by membrane bioreactor treatment and ozonation.
AB  - A set of three benzotriazole corrosion inhibitors was analyzed by liquid
      chromatography-mass spectrometry in wastewaters and in a partially closed water
      cycle in the Berlin region. Benzotriazole (BTri) and two isomers of tolyltriazole
      (TTri) were determined in untreated municipal wastewater with mean dissolved
      concentrations of 12 microg/L (BTri), 2.1 microg/L (4-TTri), and 1.3 microg/L (5
      TTri). Removal in conventional activated sludge (CAS) municipal wastewater
      treatment ranged from 37% for BTri to insignificant removal for 4-TTri. In
      laboratory batch tests 5-TTri was mineralized completely and 4-TTri was
      mineralized to only 25%. This different behavior of the three benzotriazoles was
      confirmed by following the triazoles through a partially closed water cycle, into
      bank filtrate used for drinking water production, where BTri (0.1 microg/L) and 4
      TTri (0.03 microg/ L) but no 5-TTri were detected after a travel time of several
      months. The environmental half-life appears to increase from 5-TTri over BTri to
      4-TTri. Treatment of municipal wastewater by a lab-scale membrane bioreactor
      (MBR) instead of CAS improved the removal of BTri and 5-TTri but could not avoid
      their discharge. Almost complete removal was achieved by ozonation of the
      treatment plant effluent with 1 mg O3/mg DOC.

PMID- 17180967
TI  - Occurrence and fate of barbiturates in the aquatic environment.
AB  - Barbiturates have been widely used as sedative hypnotics in the mid-1960s and
      since then mainly as veterinary drugs. To monitor their presence and fate in the
      aquatic environment, a method based on gas chromatography-mass spectrometry (GC
      MS) has been developed to quantify butalbital, secobarbital, hexobarbital,
      aprobarbital, phenobarbital, and pentobarbital, all with a limit of detection
      (LOD) down to 1 ng/L. From the various investigated waste and surface water
      samples, barbiturates were only, but regularly detected in the Mulde, a tributary
      of the river Elbe in Germany at relevant concentrations up to several microg/L.
      Investigations of groundwater being affected with wastewater infiltration several
      decades ago also revealed a barbiturate pattern, indicating a strong
      recalcitrance of these drugs. To confirm this hypothesis, studies were carried
      out on biotic and abiotic degradation. Both, the biodegradability under aerobic
      conditions and hydrolysis did not show any degradation, implementing, that the
      investigated barbiturates, once released into the aquatic environment, show high
      stability over a long period of time.

PMID- 17180968
TI  - Survey of organic wastewater contaminants in biosolids destined for land
      application.
AB  - In this study, the presence, composition, and concentrations of organic
      wastewater contaminants (OWCs) were determined in solid materials produced during
      wastewater treatment. This study was undertaken to evaluate the potential of
      these solids, collectively referred to as biosolids, as a source of OWCs to soil
      and water in contact with soil. Nine different biosolid products, produced by
      municipal wastewater treatment plants in seven different states, were analyzed
      for 87 different OWCs. Fifty-five of the OWCs were detected in at least one
      biosolid product. The 87 different OWCs represent a diverse cross section of
      emerging organic contaminants that enter wastewater treatment plants and may be
      discharged without being completely metabolized or degraded. A minimum of 30 and
      a maximum of 45 OWCs were detected in any one biosolid. The biosolids used in
      this study are produced by several production methods, and the plants they
      originate from have differing population demographics, yet the percent
      composition of total OWC content, and of the most common OWCs, typically did not
      vary greatly between the biosolids tested. The summed OWC content ranged from 64
      to 1811 mg/kg dry weight. Six biosolids were collected twice, 3-18 months apart,
      and the total OWC content of each biosolid varied by less than a factor of 2.
      These results indicate that the biosolids investigated in this study have OWC
      compositions and concentrations that are more similar than different and that
      biosolids are highly enriched in OWCs (as mass-normalized concentrations) when
      compared to effluents or effluent-impacted water. These results demonstrate the
      need to better describe the composition and fate of OWCs in biosolids since about
      50% of biosolids are land applied and thus become a potentially ubiquitous
      nonpoint source of OWCs into the environment.

PMID- 17180969
TI  - Kinetics of oxytetracycline reaction with a hydrous manganese oxide.
AB  - Tetracycline antibiotics comprise a class of broad spectrum antimicrobial agents
      finding application in human therapy, animal husbandry, aquaculture, and fruit
      crop production. To better understand the processes affecting these antibiotics
      in soils and sediments, the kinetics of oxytetracycline transformation by a
      hydrous manganese oxide (MnO2) were investigated as a function of reactant
      concentration, pH, and temperature. Oxytetracycline was rapidly degraded by MnO2.
      Initial reaction rates exhibited pronounced pH-dependence, increasing as pH
      decreased. Reaction of oxytetracycline with MnO2 was accompanied by generation of
      Mn(II) ions, suggesting oxidative transformation of the antibiotic. At pH 5.6,
      apparent reaction orders for oxytetracycline and MnO2 were 0.7 and 0.8. Reaction
      order with respect to H+ was 0.6 between pH 4 and 9. Initial reaction rates
      increased by a factor of approximately 2.4 for 10 degrees C temperature
      increases; the apparent activation energy (60 kJ x mol(-1)) was consistent with a
      surface-controlled reaction. Reactivity of tetracycline antibiotics toward MnO2
      increased in the following order: rolitetracyline oxytetracycline < or
      =tetracycline approximately meclocycline < chlortetracycline. The initial rate of
      chlortetracycline degradation by MnO2 was substantially larger than that of the
      other tetracycline antibiotics investigated. MnO2 reactivity toward
      oxytetracycline decreased with time; a retarded rate equation was used to
      describe oxytetracycline reaction with MnO2 under declining rate conditions. This
      study indicates that natural manganese oxides in soils and sediments are likely
      to promote appreciable degradation of tetracycline antibiotics, and that reaction
      rates are strongly dependent on reaction time scale and solution conditions.

PMID- 17180970
TI  - Oxidation of sulfonamide antimicrobials by ferrate(VI) [Fe(VI)O4(2-)].
AB  - Sulfonamide antimicrobials are used in both human therapy and animal husbandry.
      Sulfonamides are not readily biodegradable and have been detected in surface
      water and in secondary wastewater effluents. The chemical oxidation of
      sulfonamides by an environmentally friendly oxidant, ferrate(VI) (Fe(VI)O4(2-),
      Fe(VI)), was conducted. The sulfonamides used in the oxidation studies were
      sulfisoxazole, sulfamethazine, sulfamethizole, sulfadimethoxine, and
      sulfamethoxazole. Kinetics of the reactions were determined as a function of pH
      (7.0-9.7) and temperature (15-45 degrees C) by a stopped-flow technique. The rate
      law for the oxidation of sulfonamides by Fe(VI) is first-order with respect to
      each reactant. The observed second-order rate constants decreased nonlinearly
      with an increase in pH and are possibly related to the protonation of Fe(VI)
      (HFeO4- <==> H+ + FeO4(2-); pK(a,HFeO4) = 7.23) and sulfonamides (SH <==> H+ + S
      ; pK(a,SH) = 5.0-7.4). The activation parameters of the reactions vary with pH
      due to temperature dependence on the protonation of Fe(VI) and sulfonamides.
      These results were used to obtain enthalpy of dissociation of sulfonamides.
      Stoichiometry and products of sulfamethoxazole (SMX) reactions with Fe(VI) were
      studied in detail using various analytical techniques to evaluate the effect of
      the oxidation process on the fate of sulfonamides in water. At a stoichiometric
      ratio of 4:1 (Fe(VI): SMX), complete removal of SMX was achieved. Analyses of
      oxidation products of the reaction as well as kinetic measurements of
      substructural models of SMX suggest that the attack of Fe(VI) occurs at the
      isoxazole moiety as well as at the aniline moiety with minimal preference. The
      results of the studies reported suggest that Fe(VI) has the potential to serve as
      a chemical oxidant for removing sulfonamides and converting them to relatively
      less toxic byproducts in water.

PMID- 17180971
TI  - Reaction kinetics and transformation of carbadox and structurally related
      compounds with aqueous chlorine.
AB  - The potential release of carbadox (CDX), a commonly used antibacterial agent in
      swine husbandry, into water systems is of a concern due to its carcinogenic and
      genotoxic effects. Until this study, the reactivity of carbadox (possessing
      quinoxaline N,N'-dioxide and hydrazone moieties) toward aqueous chlorine has
      yetto be investigated in depth. Chemical reactivity, reaction kinetics, and
      transformation pathways of carbadox and structurally related compounds with free
      chlorine under typical water treatment conditions were determined. This study
      found that only CDX and desoxycarbadox (DCDX), a main metabolite of CDX with no
      ring N-oxide groups, react rapidly with free chlorine while other structurally
      related compounds including olaquindox, quindoxin, quinoxaline N-oxide,
      quinoxaline, and quinoline N-oxide do not. The reaction kinetics of CDX and DCDX
      with chlorine are highly pH dependent (e.g., the apparent second-order rate
      constant, kapp, for CDX ranges from 51.8 to 3.15 x 10(4) M(-1)s(-1) at pH 4-11).
      The high reactivity of CDX and DCDX to chlorine involves deprotonation of their
      hydrazone N-H moieties where initial chlorine attack results in a reactive
      intermediate that is further attacked by nucleophiles in the matrix to yield non
      chlorinated, hydroxylated, and larger molecular weight byproducts. All of the
      CDX's byproducts retain their biologically active N-oxide groups, suggesting that
      they may remain as active antibacterial agents.

PMID- 17180972
TI  - Water hardness as a photochemical parameter: tetracycline photolysis as a
      function of calcium concentration, magnesium concentration, and pH.
AB  - The environmental photochemical kinetics of the antibiotic compound tetracycline
      were investigated. The aqueous speciation of tetracycline over a range of natural
      pH and water hardness values is dominated by association with Ca2+ and Mg2+ ions.
      The association constants necessary to calculate tetracycline aqueous speciation
      given knowledge of pH, [Ca2+], and [Mg2+] were measured by spectrophotometric
      titrations and matrix deconvolution of a series of UV-vis absorption spectra into
      individual component species. A series of photolysis experiments was performed
      under simulated sunlight, and quantum yields for the solar photolysis of each
      environmentally relevant species were calculated. The results indicate that the
      pseudo-first-order rate constant for tetracycline photolysis at varied Mg2+ and
      Ca2+ concentrations relevant to natural conditions can vary by up to an order of
      magnitude. A self-sensitization effect was observed and was accounted for by
      varying the initial tetracycline concentration under each set of photolysis
      conditions.

PMID- 17180973
TI  - Occurrence and fate of the cytostatic drugs cyclophosphamide and ifosfamide in
      wastewater and surface waters.
AB  - The two oxazaphosphorine compounds cyclophosphamide and ifosfamide are important
      cytostatic drugs used in the chemotherapy of cancer and in the treatment of
      autoimmune diseases. Their mechanism of action, involving metabolic activation
      and unspecific alkylation of nucleophilic compounds, accounts for genotoxic
      effects described in the literature and is reason for environmental concern. The
      occurrence and fate of cyclophosphamide and ifosfamide were studied in wastewater
      treatment plants (WWTPs) and surface waters in Switzerland, using a highly
      sensitive analytical method based on solid-phase extraction and liquid
      chromatography tandem mass spectrometry. The compounds were detected in untreated
      and treated wastewater at concentrations of <0.3-11 ng/L, which corresponded well
      with concentrations predicted from consumption data and typical renal excretion
      rates. Weekly loads determined in influent and effluent wastewater were
      comparable and suggested a high persistence in WWTPs. Furthermore, no degradation
      was observed in activated sludge incubation experiments within 24 h at
      concentrations of approximately 100 ng/L. Processes that may be relevant for
      elimination in natural waterbodies were studied with a set of incubation
      experiments in the laboratory. After extrapolation to natural conditions in
      surface waters, a slow dark-chemical degradation (half-lives on the order of
      years) is the most important transformation process. Degradation by
      photochemically formed HO* radicals may be of some relevance only in shallow,
      clear, and nitrate-rich waterbodies but could be further exploited for
      elimination of these compounds by advanced oxidation processes, i.e., in a
      treatment of hospital wastewater. In surface waters, concentrations ranged from <
      or =50 to 170 pg/L and were thus several orders of magnitude lower than the
      levels at which acute ecotoxicological effects have been reported in the
      literature (mg/L range). However, due to a lack of studies on chronic effects on
      aquatic organisms and data on occurrence and effects of metabolites, a final risk
      assessment cannot be made.

PMID- 17180974
TI  - Sorption of perfluorinated surfactants on sediments.
AB  - The sorption of anionic perfluorochemical (PFC) surfactants of varying chain
      lengths to sediments was investigated using natural sediments of varying iron
      oxide and organic carbon content. Three classes of PFC surfactants were evaluated
      for sorptive potential: perfluorocarboxylates, perfluorosulfonates, and
      perfluorooctyl sulfonamide acetic acids. PFC surfactant sorption was influenced
      by both sediment-specific and solution-specific parameters. Sediment organic
      carbon, rather than sediment iron oxide content, was the dominant sediment
      parameter affecting sorption, indicating the importance of hydrophobic
      interactions. However, sorption also increased with increasing solution [Ca2+]
      and decreasing pH, suggesting that electrostatic interactions play a role.
      Perfluorocarbon chain length was the dominant structural feature influencing
      sorption, with each CF2 moiety contributing 0.50-0.60 log units to the measured
      distribution coefficients. The sulfonate moiety contributed an additional 0.23
      log units to the measured distribution coefficient, when compared to carboxylate
      analogs. In addition, the perfluorooctyl sulfonamide acetic acids demonstrated
      substantially stronger sorption than perfluorooctane sulfonate (PFOS). These data
      should prove useful for modeling the environmental fate of this class of
      contaminants.

PMID- 17180975
TI  - Attenuation of wastewater-derived contaminants in an effluent-dominated river.
AB  - Although wastewater-derived chemical contaminants undergo transformation through
      a variety of mechanisms, the relative importance of processes such as
      biotransformation and photolysis is poorly understood under conditions
      representative of large rivers. To assess attenuation rates under conditions
      encountered in such systems, samples from the Trinity River were analyzed for a
      suite of wastewater-derived contaminants during a period when wastewater effluent
      accounted for nearly the entire flow of the river over a travel time of
      approximately 2 weeks. While the concentration of total adsorbable organic
      iodide, a surrogate for recalcitrant X-ray phase contrast media in wastewater,
      was approximately constant throughout the river, concentrations of
      ethylenediamine tetraacetate, gemfibrozil, ibuprofen, metoprolol, and naproxen
      all decreased between 60% and 90% as the water flowed downstream. Comparison of
      attenuation rates estimated in the river with rates measured in laboratory-scale
      microcosms suggests that biotransformation was more important than photolysis for
      most of the compounds. Further evidence for biotransformation in the river was
      provided by measurements of the enantiomeric fraction of metoprolol, which showed
      a gradual decrease as the water moved downstream. Results of this study indicate
      that natural attenuation can result in significant decreases in concentrations of
      wastewater-derived contaminants in large rivers.

PMID- 17180976
TI  - Partitioning and bioaccumulation of PBDEs and PCBs in Lake Michigan.
AB  - Water from Lake Michigan and fish from all five Great Lakes have been sampled and
      analyzed for a suite of six polybrominated diphenyl ether (PBDE) congeners and
      110 polychlorinated biphenyl congeners (PCBs). The Lake Michigan dissolved phase
      PBDE congener concentrations (0.2 to 10 pg/L) are similar to dissolved phase PCB
      congener concentrations (nondetected to 13 pg/L). Partitioning of PBDEs between
      the particulate and dissolved phases exhibits behavior similar to that of PCBs.
      Organic-carbon-normalized water-particle partition coefficients (log K(OC)s)
      ranged from 6.2 to 6.5. Lake trout are depleted in BDE-99 relative to dissolved
      phase concentrations, and in contrast to what is expected from the PCB congener
      patterns. This reflects suspected debromination of BDE-99 in the food web of Lake
      Michigan. A regression of the log of the bioaccumulation factor (BAF) and the log
      of the octanol-water partition coefficent (K(OW)) indicated a positive
      relationship for both PCB congeners and PBDE congeners. BDE-99 does not appear to
      followthe same trend, a further indication that it is subject to
      biotransformation. Using the PBDE BAFs for Lake Michigan and the PBDE fish
      concentrations from the other Great Lakes it is expected that the dissolved phase
      concentrations of congeners in the other lakes would range from 0.04 to
      approximately 3 pg/L.

PMID- 17180977
TI  - Comparison of antimony behavior with that of arsenic under various soil redox
      conditions.
AB  - The oxidation states and host phases of Sb and As in soil samples of mine tailing
      (Ichinokawa mine, Ehime, Japan) and in laboratory soil-water systems were
      determined by X-ray absorption fine structure (XAFS) spectroscopy. HPLC-ICP-MS
      was used for speciation of Sb and As in soil water. In the Ichinokawa soil water
      system, Sb was present exclusively as the oxidized form, Sb(V), over a wide redox
      range (from Eh = 360 to -140 mV, pH 8), while As was present as a mixture of
      As(III) and As(V). This finding was confirmed in the laboratory experiments.
      These results suggest that Sb(V) is a very stable form in the environment and
      that Sb is oxidized at more negative Eh than As. Combining the results of Fe and
      Mn XAFS analyses and a positive correlation among Sb, As, and Fe abundances in
      the soil, the host phases of Sb and As in soil were Fe(III) hydroxide. XAFS
      analyses of Sb and As are also consistent with this finding. Under reducing
      conditions, the concentration of As in the soil water increased whereas that of
      Sb decreased in both the Ichinokawa and laboratory systems. This suggests that
      this contrasting behavior is controlled mainly by the different redox properties
      of Sb and As.

PMID- 17180978
TI  - Sorption of Sb(III) and Sb(V) to goethite: influence on Sb(III) oxidation and
      mobilization.
AB  - Antimony is an element of growing interest for a variety of industrial
      applications, even though Sb compounds are classified as priority pollutants by
      the Environmental Protection Agency of the United States. Iron (Fe) hydroxides
      appear to be important sorbents for Sb in soils and sediments, but mineral
      surfaces can also catalyze oxidation processes and may thus mobilize Sb. The aim
      of this study was to investigate whether goethite immobilizes Sb by sorption or
      whether Sb(III) adsorbed on goethite is oxidized and then released. The sorption
      of both Sb(III) and Sb(V) on goethite was studied in 0.01 and 0.1 M KClO4 M
      solutions as a function of pH and Sb concentration. To monitor oxidation
      processes Sb species were measured in solution and in the solid phase. The
      results show that both Sb(III) and Sb(V) form inner-sphere surface complexes at
      the goethite surface. Antimony(III) strongly adsorbs on goethite over a wide pH
      range (3-12), whereas maximum Sb(V) adsorption is found below pH 7. At higher
      ionic strength, the desorption of Sb(V) is shifted to lower pH values, most
      likely due to the formation of ion pairs KSb(OH)6 degrees. The sorption data of
      Sb(V) can be fitted by the modified triple-layer surface complexation model.
      Within 7 days, Sb(III) adsorbed on goethite is partly oxidized at pH 3, 5.9 and
      9.7. The weak pH-dependence of the rate coefficients suggests that adsorbed
      Sb(III) is oxidized by 02 and that the coordination of Sb(III) to the surface
      increases the electron density of the Sb atom, which enhances the oxidation
      process. At pH values below pH 7, the oxidation of Sb(III) did not mobilize Sb
      within 35 days, while 30% of adsorbed Sb(III) was released into the solution at
      pH 9.9 within the same time. The adsorption of Sb(III) on Fe hydroxides over a
      wide pH range may be a major pathway for the oxidation and release of Sb(V).

PMID- 17180979
TI  - Prioritization of pesticide environmental transformation products in drinking
      water supplies.
AB  - Receiving waters within catchments may be exposed to many different
      transformation products following the application of pesticides. As environmental
      waters are abstracted for drinking water treatment these compounds may pose a
      risk to human health. This paper describes a prioritization approach for
      identifying the most important transformation products in drinking water sources.
      The approach can be applied to different geographical areas that have suitable
      pesticide usage data. The risk based approach incorporates data on pesticide
      usage and toxicity as well as transformation product formation, mobility, and
      persistence. The application of the approach is illustrated for two geographical
      areas that have good quality pesticide usage data: Great Britain and California.
      The transformation products with the highest risk index and a complete
      experimentally derived data set for Great Britain were 3,5,6-trichloro-2
      pyridinol, thifensulfuron acid, and kresoxim-methyl acid and for California were
      carbendazim, aldicarb sulfoxide, and RP30228.

PMID- 17180980
TI  - Modeling the formation of N-nitrosodimethylamine (NDMA) from the reaction of
      natural organic matter (NOM) with monochloramine.
AB  - This paper presents mechanistic studies on the formation of NDMA, a newly
      identified chloramination disinfection byproduct, from reactions of
      monochloramine with natural organic matter. A kinetic model was developed to
      validate proposed reactions and to predict NDMA formation in chloraminated water
      during the time frame of 1-5 days. This involved incorporating NDMA formation
      reactions into an established comprehensive model describing the oxidation of
      humic-type natural organic matter by monochloramine. A rate-limiting step
      involving the oxidation of NOM is theorized to control the rate of NDMA formation
      which is assumed to be proportional to the rate of NOM oxidized by
      monochloramine. The applicability of the model to describe NDMA formation in the
      presence of three NOM sources over a wide range in water quality (i.e., pH, DOC,
      and ammonia concentrations) was evaluated. Results show that with accurate
      measurement of monochloramine demand for a specific supply, NDMA formation could
      be modeled over an extended range of experimental conditions by considering a
      single NOM source-specific value of thetaNDMA, a stoichiometric coefficient
      relating the amount of NDMA produced to the amount of NOM oxidized, and several
      kinetic parameters describing NOM oxidation. Furthermore, the oxidation of NOM is
      the rate-limiting step governing NDMA formation. This suggests that NDMA
      formation over a 1-5 day time frame may be estimated from information on the
      chloramine or free chlorine demand of the NOM and the source-specific linear
      relationship between this demand and NDMA formation. Although the proposed model
      has not yet been validated for shorter time periods that may better characterize
      the residence time in some distribution systems, the improved understanding of
      the important reactions governing NDMA formation and the resulting model should
      benefit the water treatment industry as a tool in developing strategies that
      minimize NDMA formation.

PMID- 17180981
TI  - Predicting the partitioning behavior of various highly fluorinated compounds.
AB  - Due to their high degree of fluorination, highly fluorinated compounds (HFCs)
      have unique substance properties that differ from many other organic
      contaminants. To predict the environmental behavior of HFCs, models that predict
      both absorptive and adsorptive partitioning are needed; however, the accuracy of
      existing models has not heretofore been thoroughly investigated for these
      compounds. This report has two parts: first we show that a well-established
      polyparameter linear free energy relationship used to predict experimental
      adsorption constants underestimates values for HFCs by several orders of
      magnitude. We found a mechanistic explanation for the model's inaccuracy and
      adjusted it accordingly. In the second part of this report, we evaluate various
      models that predict saturated subcooled liquid vapor pressure (pL*), air-water
      partition constant (Kaw), and the octanol-water partition constant (Kow) based on
      molecular structure. These parameters are typically required for general
      environmental fate and transport models. Here, we found that SPARC and COSMOtherm
      make predictions usually within 1 order of magnitude of the experimental value,
      while the commonly used EPI SUITE and ClogP perform more inaccurately. The least
      accurate predictions occurred with ClogP for the fluorotelomer alcohols, where
      the estimated values were off by 2 to almost 5 orders of magnitude.

PMID- 17180982
TI  - Quantitative determination of 1,4-dioxane and tetrahydrofuran in groundwater by
      solid phase extraction GC/MS/MS.
AB  - Groundwater contamination by cyclic ethers, 1,4-dioxane (dioxane), a probable
      human carcinogen, and tetrahydrofuran (THF), a co-contaminant at many chlorinated
      solvent release sites, are a growing concern. Cyclic ethers are readily
      transported in groundwater, yet little is known about their fate in environmental
      systems. High water solubility coupled with low Henry's law constants and octanol
      water partition coefficients make their removal from groundwater problematic for
      both remedial and analytical purposes. A solid-phase extraction (SPE) method
      based on activated carbon disks was developed for the quantitative determination
      of dioxane and THF. The method requires 80 mL samples and a total of 1.2 mL of
      solvent (acetone). The number of steps is minimized due to the "in-vial" elution
      of the disks. Average recoveries for dioxane and THF were 98% and 95%,
      respectively, with precision, as indicated by the relative standard deviation of
      <2% to 6%. The method quantitation limits are 0.31 microg/L for dioxane and 3.1
      microg/L for THF. The method was demonstrated by analyzing groundwater samples
      for dioxane and THF collected during a single sampling campaign at a TCA-impacted
      site. Dioxane concentrations and areal extent of dioxane in groundwater were
      greater than those of either TCA or THF.

PMID- 17180983
TI  - Analysis of pharmaceuticals in water by isotope dilution liquid
      chromatography/tandem mass spectrometry.
AB  - A method has been developed for the trace analysis of 15 pharmaceuticals, four
      metabolites of pharmaceuticals, three potential endocrine disruptors, and one
      personal care product in various waters. The method employs solid-phase
      extraction (SPE) and liquid chromatography/tandem mass spectrometry (LC-MS/MS),
      using electrospray ionization (ESI) in both positive and negative modes. Unlike
      many previous LC-MS/MS methods, which suffer from matrix suppression, this method
      uses isotope dilution for each compound to correct for matrix suppression, as
      well as SPE losses and instrument variability. The method was tested in five
      matrices, and results indicate that the method is very robust. Matrix spike
      recoveries for all compounds were between 88 and 106% for wastewater influent, 85
      and 108% for wastewater effluent, 72 and 105% for surface water impacted by
      wastewater, 96 and 113% for surface water, and 91 and 116% for drinking water.
      The method reporting limits for all compounds were between 0.25 and 1.0 ng/L,
      based on 500 mL of sample extracted and a final extract volume of 500 microL.
      Occurrence of the compounds in all five matrices is also reported.

PMID- 17180984
TI  - Simultaneous determination of psychoactive drugs and their metabolites in aqueous
      matrices by liquid chromatography mass Spectrometry.
AB  - A multi-residue method was developed that allows for the simultaneous
      determination of psychoactive compounds such as opioids, tranquilizers,
      antiepileptics (primidone, carbamazepine plus two metabolites),the cocaine
      metabolite benzoylecgonine, the antidepressant doxepin, as well as the calcium
      channel blocker verapamil in raw and treated wastewater, surface water,
      groundwater, and drinking water. After solid-phase extraction with Oasis HLB at
      neutral pH, the analytes were detected by LC electrospray tandem MS in the
      positive ion mode. With a few exceptions relative recoveries of the analytes
      exceeded 70%. The limits of quantification were in the low ng/L range. Matrix
      effects were compensated by using appropriate deuterated or 13C-15N-labeled
      surrogate standards. For raw and treated wastewater, concentration factors were
      lowered to reduce matrix effects. Most analytes (15 of 20) were found in raw and
      treated wastewater as well as in surface water, and hence, are presumably
      ubiquitously present in the environment. Antiepileptics, the opium alkaloids
      morphine and codeine, dihydrocodeine, the two tranquilizers oxazepam and
      temazepam, the opioid tramadol, doxepin, and verapamil were detected in STP
      discharges and German rivers at concentrations up to the microg/L range. In
      drinking water, only carbamazepine, its metabolite 10,11-dihydroxy-10,11
      dihydrocarbamazepine, and primidone were present at concentrations up to 0.020
      microg/L.

PMID- 17180985
TI  - Metal-catalyzed reduction of N-nitrosodimethylamine with hydrogen in water.
AB  - There is considerable need for the rapid destruction of N-nitrosodimethylamine
      (NDMA) in water because current alternative treatment methods are relatively
      inefficient. Powdered metal catalysts in conjunction with hydrogen gas showed
      notable potential for rapid destruction of N-nitrosodimethylamine (NDMA) in
      water. Palladium, copper-enhanced palladium, and nickel catalysts showed
      significant efficacy for NDMA reduction, with observed half-lives on the order of
      hours using 10 mg L(-1) catalyst metal. Other catalysts were screened because of
      their well-documented efficacy for reduction of halogenated hydrocarbons,
      including zerovalent iron, nickel-enhanced iron, nickel, and manganese. Starting
      with 100 microg L(-1) NDMA, a level observed at multiple field sites, pseudo
      first-order kinetics were observed for all catalysts tested. No reaction
      intermediates were observed in any experiment; the amine group of NDMA was
      cleaved and reduced to dimethylamine with carbon balance in excess of 97%.
      Reductive catalysis may prove an efficient technology for mitigating the health
      risk posed by NDMA; this study provides the foundation for mechanistic and
      longevity research.

PMID- 17180986
TI  - Effect of process variables and natural organic matter on removal of microcystin
      LR by PAC-UF.
AB  - The release of cyanobacterial toxins, such as microcystin-LR, in drinking water
      supplies is of increasing concern. In this study, we investigated the use of
      ultrafiltration (UF) combined with adsorption on powdered activated carbon (PAC)
      for the removal of microcystin-LR from drinking water. Process variables examined
      included PAC type, PAC dosage, membrane characteristics (material and pore size),
      and the presence of natural organic matter (NOM). Due to greater mesopore volume,
      wood-based activated carbon was up to 4-times more effective at removing
      microcystin-LR than coconut-based carbon, depending on contact time. Cellulose
      acetate (CA) membranes with a molecular weight cutoff (MWCO) of 20,000 Da did not
      reject or adsorb microcystin-LR. Membranes composed of polyethersulfone (PES) of
      similar pore size, on the other hand, adsorbed microcystin-LR presumably through
      hydrophobic interactions. A PES membrane with a MWCO of 5000 Da sorbed
      microcystin-LR, and also rejected 8.4% of the toxin through a size exclusion
      mechanism. When PAC was coupled to UF using PES membranes, greater removal of
      microcystin-LR occurred compared to when CA membranes were used due to sorption
      of the toxin to the PES membrane surface. The presence of Suwannee River fulvic
      acid (SRFA) reduced microcystin-LR removal by PAC-UF, primarily due to
      competition between SRFA and microcystin-LR for sites on the PAC surface.

PMID- 17180987
TI  - Use of reverse osmosis membranes to remove perfluorooctane sulfonate (PFOS) from
      semiconductor wastewater.
AB  - Perfluorooctane sulfonate (PFOS) and related substances are persistent,
      bioaccumulative, and toxic, and thus of substantial environmental concern. PFOS
      is an essential photolithographic chemical in the semiconductor industry with no
      substitutes yet identified. The industry seeks effective treatment technologies.
      The feasibility of using reverse osmosis (RO) membranes for treating
      semiconductor wastewater containing PFOS has been investigated. Commercial RO
      membranes were characterized in terms of permeability, salt rejection, scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), and membrane
      surface zeta potential (streaming potential measurements). Filtration tests were
      performed to determine the membrane flux and PFOS rejection. Over a wide range of
      feed concentrations (0.5 - 1500 ppm), the RO membranes generally rejected 99% or
      more of the PFOS. Rejection was better for tighter membranes, but was not
      affected by membrane zeta potential. Flux decreased with increasing PFOS
      concentration. While the flux reduction was severe for a loose RO membrane
      probably due to its higher initial flux, very stable flux was maintained for
      tighter membranes. At a very high feed concentration (about 500 ppm), all the
      membranes exhibited an identical stable flux. Isopropyl alcohol, present in some
      semiconductor wastewaters, had a detrimental effect on membrane flux. Where
      present it needs to be removed from the wastewater prior to using RO membranes.

PMID- 17180989
TI  - Occurrence and fate of organic contaminants during onsite wastewater treatment.
AB  - Onsite wastewater treatment systems serve approximately 25% of the U.S.
      population. However, little is known regarding the occurrence and fate of organic
      wastewater contaminants (OWCs), including endocrine disrupting compounds, during
      onsite treatment. A range of OWCs including surfactant metabolites, steroids,
      stimulants, metal-chelating agents, disinfectants, antimicrobial agents, and
      pharmaceutical compounds was quantified in wastewater from 30 onsite treatment
      systems in Summit and Jefferson Counties, CO. The onsite systems represent a
      range of residential and nonresidential sources. Eighty eight percent of the 24
      target compounds were detected in one or more samples, and several compounds were
      detected in every wastewater sampled. The wastewater matrices were complex and
      showed unique differences between source types due to differences in water and
      consumer product use. Nonresidential sources generally had more OWCs at higher
      concentrations than residential sources. Additional aerobic biofilter-based
      treatment beyond the traditional anaerobic tank-based treatment enhanced removal
      for many OWCs. Removal mechanisms included volatilization, biotransformation, and
      sorption with efficiencies from <1% to >99% depending on treatment type and
      physicochemical properties of the compound. Even with high removal rates during
      confined unit onsite treatment, OWCs are discharged to soil dispersal units at
      loadings up to 20 mg/m2/d, emphasizing the importance of understanding removal
      mechanisms and efficiencies in onsite treatment systems that discharge to the
      soil and water environments.

PMID- 17180988
TI  - Fluorochemical mass flows in a municipal wastewater treatment facility.
AB  - Fluorochemicals have widespread applications and are released into municipal
      wastewater treatment plants via domestic wastewater. A field study was conducted
      at a full-scale municipal wastewater treatment plant to determine the mass flows
      of selected fluorochemicals. Flow-proportional, 24 h samples of raw influent,
      primary effluent, trickling filter effluent, secondary effluent, and final
      effluent and grab samples of primary, thickened, activated, and anaerobically
      digested sludge were collected over 10 days and analyzed by liquid chromatography
      electrospray-ionization tandem mass spectrometry. Significant decreases in the
      mass flows of perfluorohexane sulfonate and perfluorodecanoate occurred during
      trickling filtration and primary clarification, while activated sludge treatment
      decreased the mass flow of perfluorohexanoate. Mass flows of the 6:2
      fluorotelomer sulfonate and perfluorooctanoate were unchanged as a result of
      wastewater treatment, which indicates that conventional wastewater treatment is
      not effective for removal of these compounds. A net increase in the mass flows
      for perfluorooctane and perfluorodecane sulfonates occurred from trickling
      filtration and activated sludge treatment. Mass flows for
      perfluoroalkylsulfonamides and perfluorononanoate also increased during activated
      sludge treatment and are attributed to degradation of precursor molecules.

PMID- 17180990
TI  - Enhanced biodegradation of iopromide and trimethoprim in nitrifying activated
      sludge.
AB  - Iopromide (an X-ray contrast agent) and trimethoprim (an antibacterial drug) are
      frequently detected pharmaceuticals in effluents of wastewater treatment plants
      (WWTPs) and in surface waters due to their persistence and high usage. Laboratory
      scale experiments showed that a significantly higher removal rate in nitrifying
      activated sludge as compared to conventional activated sludge was observed for
      both iopromide and trimethoprim. When the activity of the nitrifying bacteria was
      inhibited, the percent removal of iopromide decreased from 97 to 86% while
      trimethoprim removal decreased from 70 to 25%. The metabolite of iopromide
      identified when nitrification was not inhibited was a dehydroxylated iopromide at
      the two side chains. However, when the nitrifying bacteria were inhibited the
      metabolite identified was a carboxylate, formed during the oxidation of the
      primary alcohol on the side chain of iopromide. These results suggest that the
      nitrifying bacteria are important in the observed biodegradation of iopromide in
      the activated sludge with higher solid retention time (SRT). Results from the
      laboratory-scale study were corroborated by the observed removal efficiencies in
      a full-scale municipal WWTP, which showed that iopromide (ranging from 0.10 to
      0.27 microg/L) and trimethoprim (ranging from 0.0.08 to 0.53 microg/L) were
      removed more effectively in the nitrifying activate sludge which has a higher SRT
      (49 days) than in the conventional activated sludge (SRT of 6 days). In
      nitrifying activated sludge, the percent removal of iopromide in the WWTP reached
      61%, while in conventional activated sludge, average removal was negligible. For
      trimethoprim, removal was limited to about 1% in the conventional activated
      sludge, while in the nitrifying activated sludge, the removal was increased to
      50%.

PMID- 17180991
TI  - Uptake of N-nitrosodimethylamine (NDMA) from water by phreatophytes in the
      absence and presence of perchlorate as a co-contaminant.
AB  - The uptake and fate of the emerging contaminants N-nitrosodimethylamine (NDMA)
      and perchlorate in phreatophytes was studied in a hydroponics system under
      greenhouse conditions. NDMA is a potent carcinogen, and perchlorate disrupts the
      functioning ofthe human thyroid gland. The rate of removal of NDMA from solution
      by rooted cuttings of black willow (Salix nigra) and hybrid poplar (Populus
      deltoides x nigra, DN34) trees varied seasonally, with faster removal in summer
      months when transpiration rates were highest. A linear correlation between the
      volume of water transpired and mass of NDMA removed from the root zone was
      observed, especially at higher NDMA concentrations. In bioreactors dosed with
      both NDMA (0.7-1.0 mg L(-1)) and perchlorate (27 mg L(-1)), no competitive uptake
      of NDMA and perchlorate was observed. While NDMA was primarily removed from
      solution by plant uptake, perchlorate was predominantly removed by
      rhizodegradation. In the presence of NDMA, a slower rate of rhizodegradation of
      perchlorate was observed, but still significantly faster than the rate of NDMA
      uptake. For experiments conducted with radiolabeled NDMA, 46.4 +/- 1.1% of the
      total 14C-activity was recovered in the plant tissues and 47.5% was
      phytovolatilized. The 46.4 +/- 1.1% recovered in the plants was distributed as
      follows: 18.8 +/- 1.4% in leaves, 15.9 +/- 5.9% in stems, 7.6 +/- 3.2% in
      branches, and 3.5 +/- 3.3% in roots. The poor extractability of NDMA with
      methanol-water (1:1 v/v) from stem and leaf tissues suggested that some fraction
      of NDMA was assimilated. The calculated transpiration stream concentration factor
      (TSCF) of 0.28 +/- 0.06 suggests that NDMA is passively taken up by
      phreatophytes, and mainly phytovolatilized.

PMID- 17180992
TI  - Removal of natural steroid hormones from wastewater using membrane contactor
      processes.
AB  - Growing demands for potable water have strained water resources and increased
      interest in wastewater reclamation for potable reuse. This interest has brought
      increased attention to endocrine-disrupting chemicals (EDCs) as emerging water
      contaminants. The effect of EDCs, and in particular natural steroid hormones, on
      humans is of heightened interest in the study of wastewater reuse in advanced
      life support systems (e.g., space missions) because they are excreted in urine
      and have high endocrine-disrupting potencies. Direct contact membrane
      distillation (DCMD) and forward osmosis (FO) are being investigated for
      wastewater treatment in space. Retention of two natural steroid hormones, estrone
      and 17beta-estradiol, by these two processes was evaluated in the current
      investigation. DCMD provided greater than 99.5% hormone rejection; DCMD also
      provided constant flux, greater than 99.9% urea and ammonia rejection, and high
      water recovery. FO provided from 77 to 99% hormone rejection depending on
      experiment duration and feed solution chemistry.

PMID- 17180993
TI  - Life-cycle effects of single-walled carbon nanotubes (SWNTs) on an estuarine
      meiobenthic copepod.
AB  - Single-walled carbon nanotubes (SWNT) are finding increasing use in consumer
      electronics and structural composites. These nanomaterials and their
      manufacturing byproducts may eventually reach estuarine systems through
      wastewater discharge. The acute and chronic toxicity of SWNTs were evaluated
      using full life-cycle bioassays with the estuarine copepod Amphiascus tenuiremis
      (ASTM method E-2317-04). A synchronous cohort of naupliar larvae was assayed by
      culturing individual larvae to adulthood in individual 96-well microplate wells
      amended with SWNTs in seawater. Copepods were exposed to "as prepared" (AP)
      SWNTs, electrophoretically purified SWNTs, or a fluorescent fraction of
      nanocarbon synthetic byproducts. Copepods ingesting purified SWNTs showed no
      significant effects on mortality, development, and reproduction across exposures
      (p < 0.05). In contrast, exposure to the more complex AP-SWNT mixture
      significantly increased life-cycle mortality, reduced fertilization rates, and
      reduced molting success in the highest exposure (10 mg x L(-1)) (p < 0.05).
      Exposure to small fluorescent nanocarbon byproducts caused significantly
      increased life-cycle mortality at 10 mg x L(-1) (p < 0.05). The fluorescent
      nanocarbon fraction also caused significant reduction in life-cycle molting
      success for all exposures (p < 0.05). These results suggest size-dependent
      toxicity of SWNT-based nanomaterials, with the smallest synthetic byproduct
      fractions causing increased mortality and delayed copepod development over the
      concentration ranges tested.

PMID- 17180994
TI  - Stable colloidal dispersions of C60 fullerenes in water: evidence for
      genotoxicity.
AB  - Stable aqueous suspensions of colloidal C60 fullerenes free of toxic organic
      solvents were prepared by two methods: ethanol to water solvent exchange
      (EthOH/nC60 suspensions) and extended mixing in water (aqu/nC60 suspensions). The
      extended mixing method resulted in the formation of larger (dp approximately 178
      nm) and less negatively charged (zeta approximately -13.5 mV) nC60 colloids than
      nC60 prepared by ethanol to water solvent exchange (dp approximately 122 nm, zeta
      approximately -31.6 mV). Genotoxicity of these suspensions was evaluated with
      respect to human lymphocytes using single-cell gel electrophoresis assay (Comet
      assay). The assay demonstrated genotoxicity for both types of suspensions with a
      strong correlation between the genotoxic response and nC60 concentration, and
      with genotoxicity observed at concentrations as low as 2.2 microg/L for aqu/nC60
      and 4.2 microg/L for EtOH/nC60. The Olive tail moments (OTM) for these two
      concentrations were 1.54 +/- 0.24 and 1.34 +/- 0.07, respectively, which in
      comparison to the negative control OTM of 0.98 +/- 0.17 is statistically
      different with a p value of at least 0.05. Aqu/nC60 suspensions elicited higher
      genotoxic response than EthOH/nC60 for the same nC60 concentration. The results
      represent the first genotoxicity data for colloidal fullerenes produced by simple
      mixing in water.

PMID- 17180995
TI  - Comparative ecotoxicological hazard assessment of beta-blockers and their human
      metabolites using a mode-of-action-based test battery and a QSAR approach.
AB  - We analyzed nontarget effects of the beta-blockers propranolol, metoprolol, and
      atenolol with a screening test battery encompassing nonspecific, receptor
      mediated, and reactive modes of toxic action. All beta-blockers were baseline
      toxicants and showed no specific effects on energy transduction nor endocrine
      activity in the yeast estrogen and androgen screen, and no reactive toxicity
      toward proteins and DNA. However, in a phytotoxicity assay based on the
      inhibition of the photosynthesis efficiency in green algae, all beta-blockers
      were 10 times more toxic than their modeled baseline toxicity. Baseline- and
      phytotoxicity effects increased with hydrophobicity. The beta-blockers showed
      concentration addition in mixture experiments, indicating a mutual specific
      nontarget effect on algae. Using literature data and quantitative structure
      activity relationships (QSAR), we modeled the total toxic potential of mixtures
      of the beta-blockers and their associated human metabolites for the phytotoxicity
      endpoint with two scenarios. The realistic scenario (I) assumes that the
      metabolites lose their specific activity and act as baseline toxicants. In the
      worst-case scenario (II) the metabolites exhibitthe same specific mode of action
      as their parent drug. For scenario (II), metabolism hardly affected the overall
      toxicity of atenolol and metoprolol, whereas propranolol's hazard potential
      decreased significantly. In scenario (I), metabolism reduced the apparent EC50 of
      the mixture of parent drug and metabolite even further. The proposed method is a
      simple approach to initial hazard assessment of pharmaceuticals and can guide
      higher tier testing. It can be applied to other classes of pollutants, e.g.,
      biocides, as well as to environmental transformation products of pollutants.

PMID- 17180996
TI  - Aquatic toxicity of nine aircraft deicer and anti-icer formulations and relative
      toxicity of additive package ingredients alkylphenol ethoxylates and 4,5-methyl
      1H-henzotriazoles.
AB  - Characterization of the effects of aircraft deicer and anti-icer fluid (ADAF)
      runoff on aquatic organisms in receiving streams is a complex issue because the
      identities of numerous toxic additives are proprietary and not publicly
      available. Most potentially toxic and endocrine disrupting effects caused by ADAF
      are due to the numerous additive package ingredients which vary among
      manufacturers and types of ADAF formulation. Toxicity investigations of nine ADAF
      formulations indicate that endpoint concentrations for formulations of different
      manufacturers are widely variable. Type IV ADAF (anti-icers) are more toxic than
      Type I (deicers) for the four organisms tested (Vibrio fischeri, Pimephales
      promelas, Ceriodaphnia dubia, and Selenastrum capricornutum). Acute toxicity
      endpoint concentrations ranged from 347 to 7700 mg/L as ADAF for Type IV and from
      1550 to 45,100 mg/L for Type I formulations. Chronic endpoint concentrations
      ranged from 70 to 1300 mg/L for Type IV and from 37 to 18,400 mg/L for Type I
      formulations. Alkylphenol ethoxylates and tolyltriazoles are two known classes of
      additives. Nonylphenol, nonylphenol ethoxylates, octylphenol, octylphenol
      ethoxylates, and 4,5-methyl-1H-benzotriazoles were quantified in the nine ADAF
      formulations, and toxicity tests were conducted with nonylphenol ethoxylates and
      4,5-methyl-1H-benzotriazoles. Toxicity units computed for glycol and these
      additives, with respect to toxicity of the ADAF formulations, indicate that a
      portion of ADAF toxicity can be explained by the known additives and glycols, but
      much of the toxicity is due to unidentified additives.

PMID- 17180997
TI  - Distribution of human polyomaviruses, adenoviruses, and hepatitis E virus in the
      environment and in a drinking-water treatment plant.
AB  - Large numbers of viruses are excreted in human feces and urine, which even at low
      concentrations may cause illness when ingested. Some of these viruses have not
      been traditionally monitored in terms of waterborne diseases and are considered
      emergent viruses, such as hepatitis E virus (HEV) and JC and BK polyomavirus
      (JCPyV and BKPyV). The high prevalence of human adenoviruses (HAdV) and
      polyomaviruses, which both show DNA genomes, in sewage from widely divergent
      areas has suggested the relevance of evaluating these viruses as possible
      indicators of viral contamination. The concentration of these viruses was
      analyzed in sewage and river water and after treatment in a drinking-water
      treatment plant including chlorination, flocculation, ozonation, and granulate
      active carbon (GAC) filtration. Samples of GAC-filtered water were collected
      before a second chlorination treatment. The river used as a source of fresh water
      presented an average concentration of 2.6 x 10(1) JCPyV and 4 x 10(2) HAdV GC
      (genome copies)/L. A removal of 2 logarithms (99%) of HAdV and JCPyV was observed
      in the drinking-water treatment plant. All the GAC-filtered water samples studied
      contained HAdV, with a mean value of 4.3 HAdV GC/L. HEV strains belonging to
      genotype 3 were frequently detected in low concentrations in urban sewage and in
      biosolids or sewage containing swine feces but not in the river water samples
      studied. The detection of viruses by molecular techniques is useful for
      genetically describe emergent viruses in community wastewaters and water
      supplies. Quantification of JCPyV and HAdV using quantitative real-time PCR
      (QPCR) may be useful for evaluating virus removal efficiency in water treatment
      plants and as an index of the virological quality of water and of the potential
      presence of human viruses.

PMID- 17180998
TI  - Genetic variation in the conservative gene region of Norovirus genogroup II
      strains in environmental and stool samples.
AB  - Noroviruses (NoVs) have been one of leading etiological agents for infectious
      gastroenteritis over the world. Gastroenteritis caused by NoVs is prevalent in
      winter season, and the contamination of the water environment with NoVs in the
      epidemic cold season is frequently reported. In contrast, the number of
      gastroenteritis patients and NoVs in the water environment are reduced during the
      nonepidemic summer season, and the year-round fate of NoVs has remained to be
      elucidated. In this study, we collected nucleotide sequences of NoV genogroup II
      (GII) from domestic sewage, sewage sludge, treated wastewater, river water, and
      stool samples of gastroenteritis patients in geographically close areas.
      Phylogenetic analysis of the obtained NoV gene revealed that six out of seven
      isolates from environmental samples and 10 out of 11 isolates from stool samples
      belong to genotype 3 (NoV GII.3) or 4 (NoV GII.4), which have been prevalent
      throughout the world. Genetic distances between the conservative gene region of
      NoV GII.4 variants implied that genetically diverse strains are likelyto occur in
      environmental samples. The evaluation of the evolutionary change of NoV gene
      obtained from environmental samples would make it possible to elucidate the year
      round fate of NoVs.

PMID- 17180999
TI  - Quantitative risk assessment of noroviruses in drinking water based on
      qualitative data in Japan.
AB  - Noroviruses are one of the major causes of viral gastroenteritis in Japan. A
      quantitative risk assessment was conducted to evaluate the health risk caused by
      this virus in drinking water. A Monte Carlo analysis was used to calculate both
      the probability of infection and the disease burden using disability-adjusted
      life years (DALYs). The concentration of noroviruses in tap water was estimated
      based on qualitative data and a most probable number (MPN) method with an assumed
      Poisson lognormal distribution. This numerical method was evaluated using two
      sets of available count data of Cryptosporidium: that collected from a river and
      that found in tap water in Japan. The dose-response relationships for noroviruses
      were estimated using assumed ID50 (10 or 100). The annual risk was higher than
      the US-EPA acceptable level (10(-4) [infection/ person-year]) but around the WHO
      level (10(-6) [DALYs/ person-year]). As suggested by others, since microbial
      concentrations are generally lognormally distributed, the arithmetic mean was
      directly related to the annual risk, suggesting that the arithmetic mean is more
      useful in representing the degree of microbial contamination than the geometric
      mean.

PMID- 17181000
TI  - Effect of intracellular resuscitation of Legionella pneumophila in Acanthamoeba
      polyphage cells on the antimicrobial properties of silver and copper.
AB  - The property of Legionella pneumophila entering into a viable but noncultivable
      (VBNC) state under drinking water conditions (50 mL, pH 7.0, and 25 degrees C)
      and the intracellular resuscitation in Acanthamoeba polyphage cells were
      investigated. Then, the survival profiles of L. pneumophila residing in the
      planktonic phase and the endosymbiosis phase against antimicrobial silver and
      copper reagents were differentially compared with the case of Pseudomonas
      aeruginosa. The number of L. pneumophila in a cultivable state was rapidly
      reduced to below the detection limit (5.0 log reduction) within 30 days of
      incubation in synthetic drinking water, while the number of L. pneumophila in a
      viable state varied in only 0.1 log reduction during the same period, and the
      levels were sustained constantly for 190 days; in contrast, P. aeruginosa
      multiplied even in drinking water and continuously maintained its cultivability
      and viabilityfor 190 days. Distinctively, the numbers of E. coli in both
      cultivable and viable states were simultaneously diminished as 3.0 log and 1.6
      log reduction. The cultivability of L. pneumophila in the VBNC state was
      recovered and started to multiply after coincubation with A. polyphage in the
      same environment (initial population of inoculated amoeba was adjusted as 1.0 x
      10(5) amoeba/ mL), and P. aeruginosa also multiplied in amoeba cells. Finally,
      the populations of L. pneumophila in the planktonic phase after 10 days
      coincubation were detected at 1.7 x 10(7) CFU/mL, and this population was
      considered to have originated from the release of bacteria residing inside amoeba
      caused by the destruction of amoeba cells. Bacteria in the planktonic phase that
      were exposed to silver and copper were completely inactivated (more than 7 log
      reduction) within 30 min, while bacteria in the endosymbiosis phase showed much
      higher resistance against the exposure to the same concentrations of silver and
      copper. L. pneumophila and P. aeruginosa in A. polyphage cells survived to levels
      of 5.6 x 10(1) and 1.1 x 10(1) CFU/mL at the silver exposure (0.1 mgAg/L) and 7.3
      x 10(3) and 6.1 x 10(4) CFU/ mL at the copper exposure (1.0 mgCu/L),
      respectively, after 7 days.

PMID- 17181001
TI  - Occurrence of infected amoebae in cooling towers compared with natural aquatic
      environments: implications for emerging pathogens.
AB  - Many species of bacteria pathogenic to humans, such as Legionella, are thought to
      have evolved in association with amoebal hosts. Several novel unculturable
      bacteria related to Legionella have also been found in amoebae, a few of which
      have been thought to be causes of nosocomial infections in humans. Because
      amoebae can be found in cooling towers, we wanted to know whether cooling tower
      environments might enhance the association between amoebae and bacterial
      pathogens of amoebae in order to identify potential "hot spots" for emerging
      human pathogens. To compare occurrence of infected amoebae in natural
      environments with those in cooling towers, 40 natural aquatic environments and 40
      cooling tower samples were examined. Logistic regression analysis determined
      variables that were significant predictors of the occurrence of infected amoebae,
      which were found in 22 of 40 cooling tower samples but in only 3 of the 40
      natural samples. An odds ratio showed that it is over 16 times more likely to
      encounter infected amoebae in cooling towers than in natural environments.
      Environmental data from cooling towers and natural habitats combined revealed
      dissolved organic carbon (DOC) and pH were predictors of the occurrence of the
      pathogens, however, when cooling tower data alone were analyzed, no variables
      accounted for the occurrence. Several bacteria have novel rRNA sequences, and
      most strains were not culturable outside of amoebae. Such pathogens of amoebae
      may spread to the environment via aerosols from cooling towers. Studies of
      emerging infectious diseases should strongly consider cooling towers as a source
      of amoeba-associated pathogens.

PMID- 17181002
TI  - Antibiotic resistance genes as emerging contaminants: studies in northern
      Colorado.
AB  - This study explores antibiotic resistance genes (ARGs) as emerging environmental
      contaminants. The purpose of this study was to investigate the occurrence of ARGs
      in various environmental compartments in northern Colorado, including Cache La
      Poudre (Poudre) River sediments, irrigation ditches, dairy lagoons, and the
      effluents of wastewater recycling and drinking water treatment plants.
      Additionally, ARG concentrations in the Poudre River sediments were analyzed at
      three time points at five sites with varying levels of urban/agricultural impact
      and compared with two previously published time points. It was expected that ARG
      concentrations would be significantly higher in environments directly impacted by
      urban/agricultural activity than in pristine and lesser-impacted environments.
      Polymerase chain reaction (PCR) detection assays were applied to detect the
      presence/absence of several tetracycline and sulfonamide ARGs. Quantitative real
      time PCR was used to further quantify two tetracycline ARGs (tet(W) and tet(O))
      and two sulfonamide ARGs (sul(I) and sul(II)). The following trend was observed
      with respect to ARG concentrations (normalized to eubacterial 16S rRNA genes):
      dairy lagoon water > irrigation ditch water > urban/agriculturally impacted river
      sediments (p < 0.0001), except for sul(II), which was absent in ditch water. It
      was noted that tet(W) and tet(O) were also present in treated drinking water and
      recycled wastewater, suggesting that these are potential pathways for the spread
      of ARGs to and from humans. On the basis of this study, there is a need for
      environmental scientists and engineers to help address the issue of the spread of
      ARGs in the environment.

PMID- 17181003
TI  - Meanwhile, healthcare issues worth watching.

PMID- 17181004
TI  - Whistleblowers: there ain't no cure, but there is prevention.
AB  - Under federal and an increasing number of state laws, disgruntled and former
      employees are given significant financial incentives to report fraud to federal
      and state regulators. This article addresses strategies for reducing the
      likelihood that your practice will be the target of a whistleblower suit.

PMID- 17181005
TI  - How to value a buy-in/buy-out.
AB  - Buy-ins and buy-outs provide an opportunity for both existing owners of medical
      practices and prospective new physicians. For physicians, buy-ins represent the
      chance to have a financial stake in the practice, under the physician control and
      direction. This article explores helpful guidelines for valuing the practice and
      provides perspective in viewing the situations of buy-in and buy-out.

PMID- 17181006
TI  - Special tips for working with new patients.
AB  - The new patient's experience of your practice from th very first time he or she
      calls your office can influence the kind of relationship you will have as well as
      the patient's satisfaction and loyalty. This article suggests specific techniques
      hat turn new patients into loyal, established ones. It provides how-to-guidance
      about scheduling appointments for new patients, pronouncing and spelling new
      patients' names properly, screening new patients' phone calls for vital
      information, establishing the authority of the doctor, telling new patients what
      to expect, ending the first contact with new patients enthusiastically, and
      rolling out the red carpet at the first appointment. This article also offers
      strategies for following up with new patients and provides sample text for
      letters to send to new patients and for developing a new-patient get-acquainted
      checklist. Finally, this article includes strategies for turning new patients
      into strong referral sources.

PMID- 17181007
TI  - Disruptive physicians...and how to deal with them.
AB  - Physician behavioral issues take a toll on medical groups, and practice leaders
      often lack the basic tools to address them. All too often, medical practice
      leaders and administrators look the other way when physicians are disruptive or
      behave inappropriately. They delay dealing with negative conduct for a variety of
      reasons and allow physicians to continue to act out in ways that would never be
      tolerated in a staff member. Much has been written about how to deal with serious
      issues in physician behavior, such as impairment and addiction. This article
      addresses how to recognize and manage less extreme and more chronic disruptive
      behaviors. It provldes the reader with comprehensive tools to identify and
      address these issues, including a "do and don't" list and a simple five-question
      test to assess in an unbiased way what steps should be taken.

PMID- 17181008
TI  - Mission statements and vision documents in medical practices.
AB  - Thoughtful, carefully constructed mission statements and vision documents serve
      both to signal the purpose of a medical practice to the public and other
      professional colleagues, and to keep the practice's providers focused on its key
      purposes. Practice culture is the primary driver ofmission and vision. We clarify
      the differences between mission statements and vision documents, and offer
      guidelines to aid in constructing them.

PMID- 17181009
TI  - When disaster strikes: getting ready for the next big one: part II.
AB  - This two-part article deals with the role of the physician when disaster strikes.
      This second part expands on the role of the physician andpractice in the
      community and details how the physician and staff can work within the network of
      the medical societies, hospital systems, government agencies, and others in the
      event of a far-reaching disaster such as Hurricane Katrina or September 11. It
      also discusses what the physician can do to educate patients as to how to prepare
      to meet a disaster.

PMID- 17181010
TI  - CPR for your AR.
AB  - Physicians' practices constantly seek to improve their cash flow by better
      managing their accounts receivable. While one "best" method to make this happen
      does not exist, practices ofall types and sizes can adopt a number of simple and
      sensible procedures to help maximize collections--and the earlier a practice
      begins the collection process, the higher the probability of optimizing the
      results. Creating easy-to-understand goals, involving the right teams,
      demonstrating progress, and fostering a culture of accountability are but a few
      ofthe ways practices can begin working toward the goal of a more positive cash
      flow for the practice.

PMID- 17181011
TI  - Using denial management techniques to maximize practice reimbursements.
AB  - In today's world of continually decreasing reimbursements and widely anticipated
      technology expenses, it is imperative that practices maximize their existing
      reimbursement rates. This article explains the basic concepts of denial
      management and offers suggestions to ensure that denial management practices are
      successfully implemented in the practice setting using either an internal or
      external billing model.

PMID- 17181012
TI  - Auditing medical records: you can't make it up.

PMID- 17181013
TI  - PROMETHEUS payment: better for patients, better for physicians.
AB  - Although pay for performance is a positive development in the history of quality
      improvement in this country, it is generally accepted that most pay-for
      performance programs do not offer a sustainable business model. PROMETHEUS
      Payment is a new approach to provider payment that is predicated on paying for
      the resources to be brought to bear to treat a patient for a condition in
      accordance with good clinical practice guidelines. It is explicitly designed to
      reduce the administrative burden on physicians in favor of improved care
      coordination and collaboration among providers without requiring them to
      financially integrate or take insurance risk.

PMID- 17181014
TI  - Computer briefs: the open triangle.

PMID- 17181015
TI  - Advanced access works! Improved patient satisfaction, access, and P4P scores.
AB  - Practices continue to struggle with patient scheduling and assuring access to
      care for their patients. Consequently, practices are seeking new, innovative ways
      to redesign practice operations to improve patient, physician, and staff
      satisfaction. One of the foundations of this redesign is Advanced Access.
      Advanced Access is a system that gives patients the ability to schedule an
      appointment with their physician when they want or need to be seen. It redesigns
      patient access and the scheduling process to increase patient throughput and the
      medical practice's capacity. This article describes the tenets and implementation
      process Advanced Access and addresses the challenges that practices face as they
      implement Advanced Access.

PMID- 17181016
TI  - The virtual connection.

PMID- 17181017
TI  - What every physician needs to know about disability insurance.
AB  - Physicians and their patients rely on disability insurance to provide economic
      protection against unforeseen illness or injury. This article discusses various
      types of disability coverage and issues that arise in disability claims both from
      the perspective of the physician as treater as well as consumer.

PMID- 17181018
TI  - Trends in the consumer price index.

PMID- 17181019
TI  - Hospital financial health: increasing staff productivity.

PMID- 17181020
TI  - Synthesizing biofunctionalized nanoparticles to image cell signaling pathways.
AB  - This minireview outlines the synthetic efforts, from our research group, to
      produce nanomaterials for use as imaging agents to study cell signaling pathways.
      An overview of our approach to the synthesis and biofunctionalization of metal,
      semiconductor, and ceramic nanomaterials is presented. The probes investigated
      include coinage metals, Cd-based, Ge(o), naturally occurring fluorescent (NOF)
      minerals, and Ln-based nanoparticles which were synthesized from novel metal
      alkoxide, amide, and alkyl precursors. We illustrate the applications of some of
      these materials as imaging probes to detect signaling pathway components and
      cellular responses to signals (apoptosis and degranulation) in inflammatory and
      cancer cells.

PMID- 17181022
TI  - Polymerization of nanocrystal quantum dot-tubulin bioconjugates.
AB  - Nanocrystal quantum dot (NQD)-tubulin bioconjugates were prepared using a two
      step crosslinking procedure. NQD-decorated microtubules were successfully
      polymerized directly from the NQD-tubulin conjugates to form nonaggregated, full
      length (several micrometers) biopolymers. However, polymerization kinetics were
      slowed in comparison with unmodified tubulin and tubulin modified with small
      molecule dyes or biotin. Association with the relatively large nanocrystals,
      therefore, interferes to some extent with tubulin's ability to polymerize. These
      results suggest that before NQDs are used extensively as fluorescent labels in
      studies of biomolecular activity, the impact of NQD bioconjugation must be well
      understood.

PMID- 17181021
TI  - Peptide coated quantum dots for biological applications.
AB  - Quantum dots (QDOTs) have been widely recognized by the scientific community and
      the biotechnology industry, as witnessed by the exponential growth of this field
      in the past several years. We describe the synthesis and characterization of
      visible and near infrared QDots--a critical step for engineering organic
      molecules like proteins and peptides for building nanocomposite materials with
      multifunctional properties suitable for biological applications.

PMID- 17181023
TI  - Detecting single quantum dot motion with nanometer resolution for applications in
      cell biology.
AB  - Quantum dots (QDs), semiconductor particles of nanometer dimension, have emerged
      as excellent fluorescent analogs in tracer experiments with single molecule
      sensitivity for bioassays. Cell imaging greatly benefits from the remarkable
      optical and physical properties of these inorganic nanocrystals: QDs are much
      brighter and exhibit a higher resistance to photobleaching than traditional
      fluorophores, and their narrow emission spectrum and flexible surface chemistry
      make them particularly suitable for multiplex imaging. Here, we have demonstrated
      the achievement of a nanometer spatial resolution on the position of a single QD
      in a simple optomechanical instrument using a high-sensitivity low-noise
      detector, an intensified CCD camera. Furthermore, nanometer variations in the
      amplitude of a QD's sinusoidal oscillations could be quantitatively distinguished
      after fast Fourier transform (FFT) based data processing. As confirmed by
      experiments where QDs were attached to the surface of bovine aortic endothelial
      cells, this method can be exploited in biology to assess molecular and
      subcellular contributions to responses such as motility, intracellular
      trafficking, and mechanotransduction, with high resolution and minimal
      disturbance to cells.

PMID- 17181024
TI  - Tissue and species differences in the application of quantum dots as probes for
      biomolecular targets in the inner ear and kidney.
AB  - Quantum dots (QDs) are useful biological probes because of the increased
      photostability and quantum efficiency they offer over organic fluorophores.
      However, toxicity concerns arise because the QD core is composed of cadmium and
      selenium, metals known to be unsafe for humans and animals. We investigated the
      feasibility of quantum dots as biological labels for imaging studies of inner ear
      and kidney, tissues that share a polarized epithelial arrangement and drug
      susceptibility. We found that methods for labeling the actin cytoskeleton of
      monolayers of cultured amphibian kidney cells (Xenopus A6) with 565 nm QD
      conjugates were not feasible with large Xenopus inner ear organs. We then
      compared the uptake of 565 nm cationic peptide-targeted and nontargeted QDs in
      live kidney cell lines (amphibian, A6 and XLK-WG; human, HEK-293). Results showed
      that targeted QDs are internalized by all three kidney cell lines, and that
      nontargeted CdSe nanocrystals are sequestered only by human kidney cells.
      CellTracker Red CMTPX confirmed the membrane integrity and viability of HEK-293
      cells that internalized QDs. Our results demonstrate species and tissue
      differences in QD uptake and labeling, and underscore the need for long-term
      studies of QD toxicity and fate in cells.

PMID- 17181025
TI  - Quantum dot as a drug tracer in vivo.
AB  - Quantum dots (QDs) have been applied to a wide range of biological studies by
      taking advantage of their fluorescence properties. There is almost no method to
      trace small molecules including medicine. Here, we used QDs for fluorescent
      tracers for medicine and analyzed their kinetics and dynamics. We conjugated QDs
      with captopril, anti-hypertensive medicine, by an exchange reaction while
      retaining the medicinal properties. We investigated the medicinal effect of QD
      conjugated captopril (QD-cap) in vitro and in vivo. We also evaluated the
      concentration and the distribution of the QD-cap in the blood and the organs with
      their fluorescence. We demonstrate that the QD-cap inhibits the activity of ACE
      in vitro. The QD-cap reduced the blood pressure of hypertensive model rats. The
      concentration of the QD-cap in the blood was measured by using the standard curve
      of the fluorescence intensity. The blood concentration of the QD-cap decrease
      exponentially and QD-cap has approximately the same half-life as that of
      captopril. In addition, the fluorescence of the QDs revealed that QD-cap
      accumulates in the liver, lungs, and spleen. We succeeded in analyzing the
      dynamics and kinetics of small molecules using fluorescence of QDs.

PMID- 17181026
TI  - Quantum dot probes for monitoring dynamic cellular response: reporters of T cell
      activation.
AB  - Antibody-conjugated quantum dots (QDs) have been used to map the expression
      dynamics of the cytokine receptor interleukin-2 receptor-alpha (IL-2Ralpha)
      following Jurkat T cell activation. Maximal receptor expression was observed 48 h
      after activation, followed by a sharp decrease consistent with IL-2R
      internalization subsequent to IL-2 engagement. Verification of T cell activation
      and specificity of QD labeling were demonstrated using fluorescence microscopy,
      ELISA, and FACS analyses. These antibody conjugates provide a versatile means to
      rapidly determine cell state and interrogate membrane associated proteins
      involved in cell signaling pathways. Ultimately, incorporation with a
      microfluidic platform capable of simultaneously monitoring several cell signaling
      pathways will aid in toxin detection and discrimination.

PMID- 17181027
TI  - Nano- and microscale holes modulate cell-substrate adhesion, cytoskeletal
      organization, and -beta1 integrin localization in SV40 human corneal epithelial
      cells.
AB  - Human corneal epithelial cells (HCECs) interface with a basement membrane in vivo
      that possesses complex nanoscale topographic features. We report that synthetic
      substrates patterned with nano- and microscale holes differentially modulate the
      proliferation, shape and adhesion of SV40 human corneal epithelial cells (SV40
      HCECs) as a function of feature size: 1) Cell proliferation was inhibited on
      nanoscale features (features size less than 800 nm in pitch) compared to
      microscale features or planar substrates in identical culture conditions. 2)
      Cells on nanoscale holes had a stellate morphology compared to those on
      microscale features that were more evenly spread. 3) Cells adhered more to
      nanoscale features than to microscale features when exposed to shear stress in a
      laminar flow chamber. Transmission electron microscopy showed that cells cultured
      on the 400 nm pitch patterns had longer and more numerous filopodia and
      retraction fibers than cells cultured on the 1600 nm pitch patterns. Immunogold
      labeling of -beta1 integrins revealed that these receptors were localized at the
      cell periphery and in the aforementioned cytoskeletal elements. Our findings
      indicate that surface discontinuities and the activation of mechanochemical cell
      signaling mechanisms may contribute to the observed responses exhibited by SV40
      HCECs cultured on nano- and microscale topography.

PMID- 17181028
TI  - All-optical switching in plant blue light photoreceptor phototropin.
AB  - We theoretically analyze all-optical switching in the recently characterized LOV2
      domain from Avena sativa (oat) phot1 phototropin, a blue-light plant
      photoreceptor, based on nonlinear intensity-induced excited-state absorption. The
      transmission of a cw probe laser beam at 660 nm corresponding to the peak
      absorption of the first excited L-state, through the LOV2 sample, is switched by
      a pulsed pump laser beam at 442 nm that corresponds to the maximum initial D
      state absorption. The switching characteristics have been analyzed using the rate
      equation approach, considering all the three intermediate states and transitions
      in the LOV2 photocycle. It is shown that for a given pump pulse intensity, there
      is an optimum pump pulsewidth for which the switching contrast is maximum. It is
      shown that the probe laser beam can be completely switched off (100% modulation)
      by the pump laser beam at 50 kW/cm2 for a concentration of 1 mM with sample
      thickness of 5.5 mm. The switching characteristics are sensitive to various
      parameters such as concentration, rate constant of L-state, peak pump intensity
      and pump pulse width. At typical values, the switch-off and switch-on time is 1.6
      and 22.3 micros, respectively. The switching characteristics have also been used
      to design all-optical NOT and the universal NOR and NAND logic gates.

PMID- 17181029
TI  - Grid-enabled high-throughput in silico screening against influenza A
      neuraminidase.
AB  - Encouraged by the success of the first EGEE biomedical data challenge against
      malaria (WISDOM), the second data challenge battling avian flu was kicked off in
      April 2006 to identify new drugs for the potential variants of the influenza A
      virus. Mobilizing thousands of CPUs on the Grid, the six-week-long high
      throughput screening activity has fulfilled over 100 CPU years of computing power
      and produced around 600 gigabytes of results on the Grid for further biological
      analysis and testing. In the paper, we demonstrate the impact of a worldwide Grid
      infrastructure to efficiently deploy large-scale virtual screening to speed up
      the drug design process. Lessons learned through the data challenge activity are
      also discussed.

PMID- 17181030
TI  - [Simply ... move!].

PMID- 17181031
TI  - [What is the athlete's heart?].
AB  - The different components of the cardiovascular system adapt to the stress related
      to physical training. These adaptations, mainly functional and partly
      morphological, concern both the heart and the vessels. They play a key role in
      physical performance improvement, especially in case of endurance sports.

PMID- 17181032
TI  - [What the cardiologist should know about physical training].
AB  - Because of the cardiovascular stresses and the potential risks of physical
      training, cardiologists are often asked to give an opinion on aptitude for sport.
      It is therefore important to understand the fundamentals of physical training.
      This is based on specific rules; general physical preparation, progressive nature
      of the activity, individualisation of training programmes, specificity of
      sporting activity, recovery times and planning of exercise. The two main types of
      training (aerobics and weight training) are used preferentially according to the
      type of sport but good aerobic capacity is required in all specialities. The
      training implies a certain physical stress and the individual has his own
      limitations. The cardiologist may help identify an imbalance between the two
      without being an expert in all sporting disciplines. In this field, the physician
      is no substitute for the coach but can help in managing the sportsman's health.

PMID- 17181033
TI  - [Specific features of the interrogation and examination of athletes].
AB  - The motivations of a physician and a competitive athlete are fundamentally
      divergent. A competitor has short-term objectives and wants to win whatever the
      cost physically and to obtain the attention of the media. The physician's
      priorities are a healthy and long life for his patient and therefore looks to the
      future with precautionary measures. Medical confidentiality is a fundamental
      ethic of the profession (which does not help the sporting journalists...). The
      physician who chooses to look after top class athletes should not lower his
      ethical principles but should absolutely understand the motivations of
      competitors.

PMID- 17181034
TI  - [Echocardiographic assessment of cardiac remodeling in the high-level football
      player].
AB  - INTRODUCTION: The aim of this study is to assess the morphological and
      hemodynamic cardiovascular changes of 24 high-level football players, using
      Doppler-echocardiography, and compare them to a similar control group. METHODS
      AND RESULTS: Twenty-four elite football players were matched to 24 normal
      subjects according to age, sex, and body surface. All participants had a clinical
      examination, resting ECG, Doppler-echocardiography and a measurement of maximal
      oxygen uptake (VO2 max). The echocardiographic variables were compared between
      two groups by the Student's t-test and other statistical tests, using the SPSS 12
      for Windows software. Compared to the control group, the wall thickness (10.49 +
      1.04 vs. 7.5 + 2.04 mm, p < 0.05), the LV end-diastolic diameter (57.1 + 3.70 vs.
      41.2 + 3.65 mm, p < 0.01) and left atrium surface (20.16 + 2.03 vs. 16.16 + 1.83
      cm2, p < 0.01) were significantly more important in football players. The LV and
      RV ejection fractions were similar in both groups. The RV long-axis diastolic
      diameter (8 + 0.5 vs. 6.5 + 1.1 mm, p < 0.01) and S-wave using DTI (0.17 + 0.02
      vs. 0.14 + 0.02, p < 0.05) were more important among football players.
      DISCUSSION: The hemodynamic and morphological changes result from an acquired
      cardiac adaptation in athletes with important endurance and resistive efforts.
      The majority of players presented an intermediate-type of remodeling, but the
      more offensive ones had an endurance-type heart, whereas the defense players had
      a resistance-type aspect. CONCLUSION: This study on the cardiac remodeling in
      high-level athletes permits to have a distinctive approach between physiological
      and pathological remodeling. This remodeling varies according to the player's
      post and exercise capacities. In a football player, a correlation between
      physical level and physical capacity is plausible.

PMID- 17181035
TI  - [Echocardiography in athletes].
AB  - Echocardiography of athletes focuses on the left ventricle: in many cases, the
      interpretation is difficult, showing features of either dilated of hypertrophic
      cardiomyopathy. Accurate analysis requires careful recording of the left
      ventricle in the fundamental mode. Diagnostic errors by excess are common:
      overestimation of the chamber size (inadequate incidence), overestimation of wall
      thickness (failure to recognise right ventricular bands or false tendons). The
      body size of the individual must be considered when interpreting the chamber
      dimensions. The diastolic left ventricular dimension is often < 60 mm but it may
      attain 70 mm. In these cases, left ventricular function must be accurately
      determined and shown to be normal, which may prove difficult as the resting left
      ventricular ejection fraction is physiologically lower in trained athletes. The
      use of stress echo (exercise left ventricular ejection fraction) and Doppler
      tissue imaging (left ventricular filling) are often indispensable. Left
      ventricular wall thickness is rarely > 13 mm. a situation where the possibility
      of hypertrophic cardiomyopathy has to be assessed. Left atrial dilatation is
      inconstant and aortic root dilatation is very unusual. The right heart chambers
      are usually globally dilated and the inferior vena cava may seem abnormally
      dilated.

PMID- 17181036
TI  - [Exercise test in athletes].
AB  - The particularities of exercise tests in athletes concern mainly the exertion
      protocols adapted to their increased physical capacities and the interpretation
      of ECG tracing which can sometimes be very special at rest and also misleading
      during exercise. In the great majority of cases, the test used is both cardiac
      and pulmonary, in order to assess the aerobic capacities, the maximal aerobic
      power, and the determination of ventilation thresholds (programming and follow-up
      of training...). More infrequently, the test is used to detect cardiovascular
      diseases, especially during a longitudinal follow-up of high-level athletes, or
      to exclude it in case of cardiovascular symptoms, atypical resting ECG or even in
      case of suspicion of disease (arrhythmia, cardiac chamber hypertrophy or dilation
      at echocardiography). In more aged sportsmen (athletes masters), exercise tests
      performed are usually required for screening coronary heart disease. In this case
      the test protocols should be more adapted for screening than for the assessment
      of sportive capacities.

PMID- 17181037
TI  - [Cardiological aspects of fatigue states in athletes].
AB  - The physical load increase during training can lead to the development of
      clinical patterns of intolerance differing according to their severity, prognosis
      and reversibility. However, they always include fatigue as a key symptom. The aim
      of this paper is to review recent data on fatigue states in sportsmen, their
      clinical presentation and diagnostic orientations. A continuum exists, from acute
      fatigue states after one or several highly-intensive training sessions, to
      overreaching, associated to performances alteration which can be easily reversed,
      and to overtraining, representing a severe clinical pattern which can hardly be
      reversed. Overreaching and overtraining are characterized by a persisting fatigue
      state, associated to performances alteration and mood disorders. In an athlete
      with unexplained alteration of performances associated to physical fatigue, the
      medical interrogation is critical, in order to check the durable character of
      sportive performances alteration, to describe the fatigue and identify risk
      factors of occurrence of overtraining (training program intensity, mental stress,
      diet factors, hypoxic training, etc.). The use of a validated and adapted
      questionnaire as the one proposed by the French Society of Sports Medicine is
      valuable. In majority, in athletes and those doing sports regularly, the
      cardiological alert signs are rare, and the clinical examination by a specialist
      is poorly contributive, except for eliminating an organic cause of fatigue.

PMID- 17181038
TI  - [Prevalence of sudden cardiac death during sports activities].
AB  - Sudden death during sport is a rare and unexpected event. It essentially affects
      young males, and a cardiomyopathy that had not been diagnosed during medical
      examinations is present in the majority of cases. In young subjects, there is
      generally hypertrophic cardiomyopathy or arhythmogenic right ventricular
      dysplasia. This is revealed during sporting activity, and sudden death is often
      the first symptom of the disease. Competitive sport increases the relative risk
      of sudden death to 2.5 compared to the risk in a non-sporting subject. The
      prevalence of sudden death during competitive sport is poorly understood. From
      the rare studies available, it could be estimated at 2.3/100,000 athletes per
      year. In Europe, it essentially occurs during football matches. However, the
      prevalence of sudden death during so-called 'recreational' sports is not
      precisely known. It could be much higher because these activities involve a
      larger number of people, and take place without supervision and usually without a
      medical examination beforehand. The participants are older, and coronary
      pathology is usually implicated.

PMID- 17181039
TI  - [Recommendations for sports participation in patients with arrhythmia].
AB  - Nowadays, sports are a wonderful mean for social success, and the high-level
      athlete is the symbol of a perfect hygiene of life. Despite this, the occurrence
      of unexplained sudden death (SD) is not exceptional, especially during training
      and competition. In this context, it is important to intensify medical controls
      for these athletes, especially in a very early phase, in order to detect subjects
      at risk. In case of detection of a cardiac disease prone to cardiovascular or
      arrhythmic event, the practice of any high-level sportive activity or even any
      sustained sportive activity must be forbidden without hesitation, with the aim of
      protecting these subjects. Even though a total interdiction of sports practice
      can be a tough decision to be accepted, it should prevail on the dramatic
      consequences of sudden death. Physicians' responsibility issues in the screening
      and management of competition or leisure-time sportsmen are of high importance
      since in case of sudden death, the physician and the medical community
      liabilities can be considered. As a consequence, the medical community set up
      recommendations on the screening, treatment and even interdiction of sportive
      activity for athletes, which should also be applied to leisure-time sportsmen. In
      the first part of this article, the different causes (especially the arrhythmia
      related) of sudden death occurring in sportsmen are reviewed. In the second part,
      the recommendations on practice of high-level sports in case of arrhythmia or
      genetic arrhythmic cardiac disease are summarized.

PMID- 17181040
TI  - [Coronary risk related to sport].
AB  - Regular physical activity is beneficial because it is associated with a 40%
      reduction in the risk of death or myocardial infarction. However, sport
      momentarily increases the risk of adverse cardiovascular events during the
      sporting activity. This increased risk is higher in the less accomplished
      sportsmen and in those with cardiovascular risk factors. Regular weekly exercise,
      even of mild to moderate intensity, has a protective effect. An adverse coronary
      event on exercise is observed in 1200 to 1500 patients per year in France. It
      results from underlying coronary artery disease which is often occult. In the
      under 35 year age group, although atherosclerotic plaque is already present, the
      possibility of a congenital anomalous coronary arterial anatomy should be
      considered. This can sometimes be detected by transoesophageal echocardiography.
      After 35 years of age, coronary arteriosclerosis is almost the only pathology
      observed. The probability of a coronary event is higher in under trained
      "veteran" with known classical cardiovascular risk factors, often occurring by
      "error" in the practice of an activity too intense for the level of physical
      fitness. It should be remembered that 50% of these complications occur in people
      who have experienced symptoms on exercise in the days or weeks before the event.
      This article also discusses which risk factors aggravate the risk in known
      coronary patients and what advice should be given to coronary patients who want
      to benefit from the effects of regular physical exercise.

PMID- 17181041
TI  - [Cardiomyopathy and sport].
AB  - Hypertrophic cardiomyopathy (HCM) remains the main cause of sudden death in top
      class sportsmen and women. In these persons, practicing over 10 hours of sport
      per week and/or engaging in competitions in the younger age group, the
      distinction between physiological and pathological left ventricular hypertrophy,
      (LVH) is usually easy. In favour of physiological LVH, the hypertrophy is
      symmetrical, < 13mm on echocardiography (12mm in women and adolescents), non
      obstructive, with normal or slightly increased left ventricular size (> or =
      55mm), only slight left atrial dilatation, mitral E/A ratio > 1 with normal
      tissue Doppler parameters, normal ECG with no symptoms or family history (HCM or
      sudden death). When left ventricular wall thickness is 13 to 15 mm, in the
      absence of these reassuring criteria, further investigations (stress ECG and
      echocardiography, Holter ECG) should be systematic, as should be a family enquiry
      and, if possible, echocardiography after stopping training in order to check
      regression of the LVH. Left ventricular wall thickness > 15mm should be
      considered HCM and sporting activities should be forbidden. The problem of
      dilated cardiomyopathy should be considered when LV diastolic diameters > 60mm
      (especially as its regression after stopping training is variable) and LV
      ejection fractions are < 50% and do not improve on exercise: other warning signs
      include regional dilatation and wall motion abnormalities, abnormal Doppler
      filling indices or a positive family history.

PMID- 17181042
TI  - [Screening for high risk cardiac diseases in athletes].
AB  - The prevention of cardiovascular complications occurring during sporting activity
      requires detection of well-known pathologies which are often clinically latent
      but which may present with sudden death. The problem of detection and the
      recommendations and French laws concerning this subject are summarised in this
      article.

PMID- 17181043
TI  - [The heart and underwater diving].
AB  - Cardiovascular examination of a certain number of candidates for underwater
      diving raises justifiable questions of aptitude. An indicative list of
      contraindications has been proposed by the French Federation of Underwater
      Studies and Sports but a physiopathological basis gives a better understanding of
      what is involved. During diving, the haemodynamic changes due not only to the
      exercise but also to cold immersion, hyperoxaemia and decompression impose the
      absence of any symptomatic cardiac disease. Moreover, the vasoconstriction caused
      by the cold and hyperoxaemia should incite great caution in both coronary and
      hypertensive patients. The contraindication related to betablocker therapy is
      controversial and the debate has not been settled in France. The danger of
      drowning makes underwater diving hazardous in all pathologies carrying a risk of
      syncope. Pacemaker patients should be carefully assessed and the depth of diving
      limited. Finally, the presence of right-to-left intracardiac shunts increases the
      risk of complications during decompressionand contraindicates underwater diving.
      Patent foramen ovale is a special case but no special investigation is required
      for its detection. The cardiologist examining candidates for underwater diving
      should take all these factors into consideration because, although underwater
      diving is a sport associated with an increased risk, each year there are more and
      more people, with differing degrees of aptitude, who wish to practice it.

PMID- 17181044
TI  - [The heart and the mountains].
AB  - In a normal subject, exposure to high altitude is accompanied by a diminution in
      performance that is proportional to the hypoxia. In order to advise a cardiac
      patient who is contemplating undertaking a physical activity in the mountains and
      wishes to avoid taking any unnecessary risks in an environment that can quickly
      become very hostile, it is important to have a recent evaluation of the
      cardiopathy, and some appreciation of the expected problems linked to the
      activity and the location. Certain pathologies are absolute contraindications to
      high altitude, such as pulmonary arterial hypertension, thrombo-embolic disease,
      and unstable cardiac disease. The majority of stable cardiopathies allow some
      modified activity. The role of the cardiologist is to evaluate the patient's
      functional capacity, to calculate the effect of altitude on this capacity, and to
      postulate whether the reserve will be sufficient to cope with the expected
      demand.

PMID- 17181045
TI  - [The heart and doping].
AB  - Doping is becoming an everyday problem in sports medicine. Its main feature is
      its universality: it concerns all sports, even the most unexpected, from cycling
      to billiards; all countries are affected with certain continental preferences
      with regards to the substances used; it is seen in all levels of competition,
      both in amateurs and professionals. Doping is observed early on, even in
      childhood. Many substances are used and they are increasingly available: all
      bodily functions are targeted: cerebral, metabolic, cardiovascular, respiratory,
      haematological and, in the near future, genetic. Detection of doping is difficult
      and unpredictable in a legislative environment which is gradually improving. The
      different modes of action of the doping substances often target the
      cardiovascular system, especially with regards to their potential complications:
      hypertension, arrhythmias, thrombosis, coronary artery and peripheral artery
      diseases and also cardiomyopathies. Every cardiologist should therefore be aware
      of the problem, even outside the context of sport, as it may impact on daily
      cardiological practice.

PMID- 17181046
TI  - [Value and limitations of sport in cardiac patients].
AB  - Regular physical exercise increases effort capacity, the quality of life, and
      improves symptoms in all cardiac patients. In addition, and much more
      importantly, all studies show a close correlation between exercise and the
      reduction of mortality and morbidity with a beneficial effect on the progression
      of atherosclerosis. This relationship is particularly well documented in patients
      with coronary artery disease. Exercise has a beneficial effect due to its action
      on all the principal coronary risk factors, an endothelial dysfunction,
      coagulability and prevention of thrombosis and an autonomic nervous system tone.
      All forms of physical activity and some sports may therefore be considered by
      these patients. In some cases, competitive sport may be permitted, in accordance
      with popular social custom. In order to obtain these cardiocirculatory
      protection, physical exercise and sporting activities should be the object of a
      personalised therapeutic prescription which takes into account the intensity, the
      type of effort, its duration and frequency. Indeed, if the intensity of the
      exercise is too low, these patients may not obtain the desired benefits. On the
      other hand, excessively intensive exercise could trigger serious adverse effects
      such as severe arrhythmias, sudden death or an acute coronary syndrome. It is,
      therefore, essential before "prescribing" exercise to perform a preliminary
      evaluation to stratify the patient's risk and in order to recommend appropriate
      and well adapted exercise programs.

PMID- 17181047
TI  - [Sports activity in heart disease: synthesis of new recommendations].
AB  - The practice of moderate and regular sports is beneficial for health, and should
      then always be promoted. The intensive practice of sports, especially for
      competition, increases the risk of cardiovascular events in patients with heart
      disease. Facing to a patient with heart disease requiring a certificate of non
      contra-indication for sports practice, the cardiologist can sometimes consider
      himself/herself helpless for managing accurately the situation. Recently,
      recommendations have been published and summarized herein, in order to guide the
      final decision.

PMID- 17181048
TI  - [Certification for non-contra-indication for sports practice: the physician's
      liability].

PMID- 17181049
TI  - Comparative analysis of direction, value, and duration atrial pressure of shifts
      caused by depressor agents.
AB  - Shifts in right- and left-atrial pressure after administration of acetylcholine,
      histamine, or isoproterenol to cats were oppositely directed in 69% cases; both
      parameters decreased in 11% cases (changes were more pronounced in the right
      atrium) and increased in 20% cases (similar shifts). Changes in the left-atrial
      pressure persisted for a longer time (compared to those in the right atrium) and
      their dynamics was similar to that of venous return and cardiac output.

PMID- 17181050
TI  - Interaction between dopamine D1 and D2 receptors in modulation of the immune
      response.
AB  - The interaction between dopamine D1 and D2 receptors plays a role in
      immunomodulation. The results of thus interaction depends on the degree of
      receptor activation with selective agonists in different doses. Combined
      treatment with agonists of D1 and D2 receptors in high doses had a synergistic
      effect in the mechanisms of immunomodulation. Receptor agonists in low doses
      suppressed the immune response. Our results suggest that weak activation of one
      of these receptors is accompanied by inactivation of the other receptor type.

PMID- 17181051
TI  - Role of Thy-1,2+ cells in hemopoiesis regulation during hypoxia.
AB  - We studied the role of Thy-1,2+ cells in the regulation of hemopoiesis during
      oxygen deficiency of different genesis. These cells of the hemopoiesis-inducing
      microenvironment play an important role in the compensatory and adaptive
      reactions of the blood system to hypoxia. Thy-1,2+ cells directly or indirectly
      (via interaction with adherent myelokaryocytes) stimulated hemopoietic
      precursors. The effect of these cells on committed erythroid precursors was most
      pronounced.

PMID- 17181052
TI  - Effect of complex phytoadaptogen on MPTP-induced Parkinson's syndrome in mice.
AB  - Oral administration of 10% solution of Phytomix-40 (multicomponent plant
      phytoadaptogen) to C57Bl/6 mice with MPTP-induced Parkinson's syndrome alleviated
      symptoms (oligokinesia and muscle rigidity), compensated for the deficiency of
      dopamine and its metabolites (DOPAC and homovanillic acid), and reduced the level
      of lipid peroxides in the striatum. In vitro Phytomix-40 in a concentration of
      3.3 x 10(-2) g/liter exhibited a pronounced antioxidant effect (5-fold decreased
      MDA level in mouse brain homogenate in Fe(2+)-ascorbate-dependent LPO).

PMID- 17181053
TI  - Deltaran prevents an adverse effect of emotional stress on the course of cerebral
      ischemia in low-resistant animals.
AB  - Local cerebral blood flow in the left hemisphere decreased most significantly in
      low-resistant Wistar rats preexposed to emotional stress. Deltaran selectively
      increased blood flow in the left hemisphere and improved blood supply to neuronal
      activity unit of the brain in these animals. This drug prevented progressive
      decrease in local cerebral blood flow in both hemispheres during the acute stage
      of ischemia. The effect of Deltaran was related to modulation of collateral blood
      flow and adequate blood supply to neuronal activity unit in the brain tissue.
      Deltaran decreased the mortality rate (by 62%) and alleviated the symptoms of
      cerebral ischemia. The positive effect of Deltaran was more pronounced in the
      left hemisphere.

PMID- 17181054
TI  - Effects of L-arginine on various types of pain sensitivity.
AB  - Intraperitoneal injection of L-arginine to male Wistar rats 12 min before the
      start of the experiment produced a nociceptive effect on models of
      electrocutaneous stimulation of the tail or hot-plate test and increased
      nociceptive behavior due to high sensitivity of supraspinal nociceptive
      structures to this compound. The nociceptive effect of this amino acid was more
      pronounced and persistent under conditions of electrocutaneous stimulation.

PMID- 17181055
TI  - Prolonged decrease in stress reactivity caused by dehydroepiandrosterone sulfate.
AB  - In male rats exposed to repeated stress, the decrease in stress reactivity
      produced by subcutaneous injection of dehydroepiandrosterone sulfate (recorded by
      the decrease in stress-induced concentrations of corticosterone and
      adrenocorticotropic hormone in blood plasma) was observed 1-6 days postinjection
      and involved central regulatory mechanisms.

PMID- 17181056
TI  - Disturbances in hormonal regulation of vascular tone during traumatic shock.
AB  - Changes in hormonal regulation of the vascular tone in Wistar rats were studied
      on Cannon model of traumatic shock. The pressor response to angiotensin II
      decreased by 30-40% 3 h after the incidence of trauma. The reaction to
      vasopressin remained unchanged. However, phenylephrine in medium and high doses
      produced a more pronounced pressor response under these conditions. One day after
      trauma we revealed a decrease in vascular sensitivity not only to angiotensin II,
      but also to vasopressin and alpha1-adrenoceptor agonist phenylephrine. The
      vascular response was observed only after treatment with phenylephrine in maximum
      doses. Traumatic shock was accompanied by inverse response to serotonin:
      hypertensive effect instead of blood pressure drop. Our results show that
      traumatic shock is accompanied by specific changes in vascular reactivity.

PMID- 17181057
TI  - Evaluation of the progeny of rats treated with topoisomerase II inhibitor
      vepesid.
AB  - Progeny of Wistar rats treated with vepesid 1, 3, and 6 months before mating is
      characterized by common pathological changes. These changes were more pronounced
      and more diverse in animals descending from females receiving the cytostatic
      compared to the progeny of treated males. The severity of toxic effects depended
      on the period between mating and vepesid treatment. Cytostatic treatment 3 months
      before mating was associated with minimum toxicity for the progeny.

PMID- 17181058
TI  - Changes on the surface of erythrocyte membrane during chronic stress in rats.
AB  - Binding of galactose-specific lectin PNA to the surface of erythrocyte membrane
      decreased by more than 90% in stressed rats. In the presence of sodium dodecyl
      sulfate, the lectin-binding fraction was electrophoretically separated into 3
      major glycoprotein subfractions with molecular weights of 25, 37, and 50 kDa.

PMID- 17181059
TI  - Neurotrophic effects of polyhydroxylated steroids and steroid glycosides in
      cultured neuroblastoma cells.
AB  - The effects of steroid compounds from Pacific Ocean starfishes were studied using
      cultured neuroblastoma C-1300 cells. Vital observations and examination of silver
      impregnated preparations showed that the test substances in a concentration of 2
      10 microM stimulate differentiation and improves survival of neuroblastoma cells
      under adverse conditions (similarly to neurotrophins). These substances in high
      concentrations (20-40 microM) had no effect or exhibited cytotoxic activity. The
      screening test allowed us to select several compounds for further studies of
      neurotrophic and neuroprotective properties.

PMID- 17181060
TI  - Effect of nitroglycerine on content of second messengers in myocytes of rat
      thoracic aorta.
AB  - We evaluated the concentration dependence and time dependence of the effect of
      nitroglycerine on intracellular content of cAMP, cGMP, and free Ca2+. It was
      shown that after norepinephrine stimulation, nitroglycerine exhibited calcium
      blocking activity in lower concentrations (starting from 10(-7) M). Under
      conditions of experimental nitrate tolerance the dose-dependent effect of
      nitroglycerine on intracellular cGMP and Ca2+ was less pronounced. Calcium
      blocking activity of nitroglycerine decreased most significantly upon stimulation
      of myocytes with norepinephrine.

PMID- 17181061
TI  - Effect of polysaccharides on the blood system in rats.
AB  - Natural plant polysaccharides stimulated hemopoiesis, increased the content of
      some macroglobulins in blood plasma, modulate the weight and cellular composition
      of lymphoid and hemopoietic organs, activated lymphopoiesis, and enhanced enzyme
      activity in healthy animals.

PMID- 17181062
TI  - Distribution of bemitil in organs and tissues of rats after single or repeated
      administration.
AB  - After single and repeated peroral administration of bemitil to rats this drug was
      found in the liver, brain, kidneys, spleen, heart, skeletal muscles, lungs,
      adipose tissue, and testicles. After single treatment accumulation of bemitil was
      most pronounced in the liver. After repeated treatment the decrease in bemitil
      concentration in the liver was probably associated with increased elimination of
      the drug from liver tissue due to intensification of its biotransformation. We
      conclude that bemitil can accumulate in the blood, but not in tissues.

PMID- 17181063
TI  - Effect of single and repeated administration of high-molecular-weight heparin in
      low doses on brain content of neurotransmitters in Wistar rats.
AB  - We demonstrated high sensitivity of the brain neurotransmitter system to high
      molecular-weight heparin in Wistar rats. Single and repeated administration of
      heparin modulated the content of monoamines and neurotransmitter amino acids in
      the hippocampus, striatum, and cerebral cortex. Antistress activity of high
      molecular-weight heparin and its positive effects on memory under experimental
      conditions suggest that this preparation in low doses can be used in the therapy
      of neurological and age-related diseases.

PMID- 17181064
TI  - Binding of zinc cations to human serum gamma-globulin.
AB  - Binding of zinc cations to human serum gamma-globulin was studied by molecular
      ultrafiltration. The content of free metal in the filtrate was evaluated by
      reaction with o-phenanthroline. Conformation characteristics of the protein were
      determined by UV spectrophotometry. Our findings suggest that gamma-globulin
      molecule contains several zinc binding sites differing by corresponding constants
      and successively occupied with increase in the content of bound metal. The
      parameters of zinc binding correspond to those obtained in experiments with
      copper. Conformation status of protein with bound zinc differs significantly from
      that of protein with bound copper cations.

PMID- 17181065
TI  - Dysregulation of apoptotic death in the pathogenesis of virus-induced cytogenetic
      instability of blood lymphocytes.
AB  - The cytogenetic status and activity of regulatory systems for stability of the
      cell genome were evaluated in patients with chronic viral persistence. Hepatitis
      B and C viruses damage the chromosome apparatus of peripheral blood lymphocytes.
      Cytogenetic instability of immunocompetent cells during chronic viral infection
      was associated with inhibition of DNA excision repair system and dysregulation of
      apoptosis in target cells.

PMID- 17181066
TI  - Analysis of genetic markers of N. gonorrhoeae resistance to beta-lactam
      antibiotics.
AB  - A complex method for detection of genetic markers of N. gonorrhoeae resistance to
      penicillin was developed. Mutations in penA and ponA genes were detected by
      minisequencing reaction with subsequent detection of reaction products by MALDI
      TOF mass spectrometry. This approach was tested on 31 clinical strains of N.
      gonorrhoeae with minimum inhibitory concentration of penicillin from 0.03 to 8
      microg/ml and higher. Mutations in penA and ponA genes in moderately resistant
      strains were shown (minimum inhibitory concentration up to 0.5 microg/ml) and
      mutations in penA, ponA, and penB genes in resistant strains (minimum inhibitory
      concentration more than 1.0 microg/ml). beta-Lactamase genes were detected in 4
      strains with high resistance (minimum inhibitory concentration 4-8 and more
      microg/ml). Correlation between microbiological resistance and presence of
      respective mutations in the studied locuses was detected.

PMID- 17181067
TI  - Phytoadaptogen correction of clinical and immunobiological parameters in patients
      with benign prostatic hyperplasia.
AB  - Correction of hormonal, immune, interferon, and antioxidant status and genetic
      abnormalities with a complex phytoadaptogen leads to positive clinical effects in
      elderly patients with benign prostatic hyperplasia.

PMID- 17181068
TI  - Study of antibody production to Tamm-Horsfall protein in renal transplant donors
      and recipients.
AB  - The content of Tamm-Horsfall protein was measured in the urine of humans without
      renal diseases, pregnant women, and donors and recipients of renal transplant
      using a new test system for measuring Tamm-Horsfall protein including antigenic
      diagnostic agent and immune serum. Production of antibodies to Tamm-Horsfall
      protein was characterized using antigen diagnostic system.

PMID- 17181069
TI  - Peculiarities of hemoglobin interaction with serum proteins of mice with Ehrlich
      carcinoma.
AB  - In male C57Bl/6 mice with transplanted Ehrlich carcinoma, hemoglobin forms a
      complex with serum proteins characterized by a molecular weight of about 300 kDa.
      The complex incorporates proteins weighing 100, 68, 65, and 15 kDa identified by
      MALDI-TOF mass spectrometry as haptoglobin, serum albumin, gi/26341396 nameless
      protein Mus musculus, and alpha-hemoglobin, respectively. This complex can
      possess biological activity and contribute to the control of tumor growth.

PMID- 17181071
TI  - Effect of GABAergic and adrenergic agents on activity of Na+/K+ pump and Cl(-)
      cotransport in somatic muscle cells of earthworm Lumbricus Terrestris.
AB  - GABA, baclofen, epinephrine, and norepinephrine hyperpolarized the membrane of
      earthworm somatic cells. This effect was prevented by furosemide, removal of Cl-
      from the medium, or activation of Na+/K+ pump by 3-fold increase external
      potassium concentration. It was hypothesized that GABA, baclofen, epinephrine,
      and norepinephrine stimulate Na+/K+ transport via specific receptor inputs, but
      their effect on resting potential can be realized only under conditions of
      working Cl- symport.

PMID- 17181070
TI  - Poly(ADP-ribose)-polymerase-1 and aging: experimental study of possible
      relationship on stationary cell cultures.
AB  - Experiments on "stationary aging" cultures of B11dii-FAF28 Chinese hamster cells
      showed that contact inhibition of cell growth and further culturing of cells in
      the stationary phase led to continuous inhibition of enzymes realizing poly-ADP
      ribosylation of chromatin proteins. Cell density in the monolayer and percentage
      of damaged cells detected by trypan blue staining decreases during this process.

PMID- 17181072
TI  - Changes in the lipid composition of blood plasma and liver in rats induced by
      severe psychic trauma.
AB  - The concentration of high-density lipoprotein cholesterol and triglycerides in
      rat serum sharply decreased after psychic trauma caused by life hazard. The
      content of these substances remained unchanged for not less than 1 week after
      trauma. The concentration of high-density lipoprotein cholesterol was low, while
      serum content of triglycerides increased 6 weeks after trauma. The concentration
      of high-density lipoprotein cholesterol significantly decreased after repeated
      psychic trauma. These changes were accompanied by a sharp increase in the
      concentration of triglycerides in the serum. Total cholesterol concentration in
      the liver decreased under these conditions.

PMID- 17181073
TI  - Structural reorganization of the rat liver under cytotoxic effect of doxorubicin.
AB  - We studied structural reorganization of the liver after toxic injury caused by a
      single injection of doxorubicin in a sublethal dose (10 mg/kg). The morphogenesis
      of doxorubicin injury to the liver is determined by two main pathogenetic
      factors: cytotoxic effect of doxorubicin and its metabolites on liver cell
      populations (primarily hepatocytes) and pronounced hemodynamic disorders in the
      greater circulation resulting from the development of chronic cardiac
      insufficiency. Changes in hepatocyte caused by doxorubicin manifest by fatty
      degeneration in the periportal zones and by pronounced lytic changes in the
      pericentral zones, most pronounced by day 30 of the experiment. Doxorubicin in
      the studied dose exhibited no cytostatic effect on the hepatocyte population.
      Hepatocyte proliferation, observed during the entire experiment, leads to an
      appreciable increase in their count and liver weight.

PMID- 17181074
TI  - Morphological and functional state of rat ovaries in the early and late periods
      after injection of vepesid.
AB  - Morphological and functional state of the ovaries in female Wistar rats was
      assessed in the early and late periods after administration of antitumor drug
      vepesid in a single maximum tolerated dose. In the early period, the drug
      pronouncedly decreased the number of primordial follicles, bi- and multilayer
      follicles, and the total number of generative elements. The number of graafian
      vesicles and corpora lutea did not decrease. In the late period, exhaustion of
      the reserved potencies of gonads was more pronounced than in the control.
      Morphological alterations in the ovaries were accompanied by inhibition of the
      functional state of the female reproductive system in the period corresponding to
      the action on mature and primordial follicles. This inhibition manifested in
      increased postimplantation mortality.

PMID- 17181075
TI  - Morphological changes in the implantation zone of Prolen and Esfil reticular
      endoprostheses.
AB  - Comparative histological and electron microscopic study of tissues in the zone of
      implantation of polypropylene endoprostheses Prolen and Esfil was carried out in
      mice. Implantation of a reticular endoprosthesis Esfil was associated with a more
      pronounced infiltration with neutrophilic granulocytes, macrophages, and
      lymphocytes. Both nets were characterized by pronounced integration in the
      adjacent tissues in the implantation zone and can be recommended for clinical
      use.

PMID- 17181076
TI  - Intracellular changes in rat hepatocytes after intratracheal administration of
      highly dispersed silicon dioxide and uridine effects on these changes.
AB  - Rat hepatocytes were examined under electron microscope at early terms after
      intratracheal administration of highly dispersed silicon dioxide powder against
      the background of uridine treatment. Penetration of powder particles into
      hepatocyte cytoplasm, nuclei, mitochondria, and peroxisomes and development of
      bacteria in these cells were observed. Uridine reduced the destructive effect of
      powder on the organelles, increased glycogen content in hepatocytes, and
      inhibited the formation of capsulated bacterial forms in these cells.

PMID- 17181077
TI  - Preparedness for influenza pandemic in Hong Kong nursing units.
AB  - BACKGROUND: To present preparedness planning for an influenza pandemic for two
      nursing subunits: nursing services in hospitals and schools of nursing in
      universities. DISCUSSION: The preparedness plan is modeled on a modified Haddon
      matrix, a logical approach to identify measures appropriate for the pre-event,
      event, and postevent phases of an influenza pandemic. For the pre-event phase,
      the objective is to ensure preparedness for the potential pandemic outbreak
      through training, communication, surveillance, infection control, and
      vaccination. Once the pandemic outbreak is declared, the aim is to implement
      effective measures to ensure a rapid and appropriate response. For the postevent
      phase, the plan is focused on the restoration of core functions, vigilance for a
      second or possibly more waves of the pandemic, and psychosocial support to staff
      and students. CONCLUSION: Measures required to prepare for, respond to, and
      manage the consequences of influenza pandemic are identified. This planning
      indicates the need to balance a logical approach with contextual perspectives and
      the importance for nursing leaders to develop plans for subunits of larger
      entities.

PMID- 17181078
TI  - Injury as a global phenomenon of concern in nursing science.
AB  - PURPOSE: To discuss injury research as a phenomenon of concern in nursing
      science. ORGANIZING CONSTRUCT: Injury is defined as the physical damage that
      results when the human body is briefly subjected to intolerable levels of energy.
      It is the leading cause of death in the first 4 decades of life in high-income
      nations and is second only to infectious diseases as a leading cause of death in
      low- and middle-income nations. METHODS: Review and discussion of relevant
      scientific and theoretical literature in both injury and nursing science.
      FINDINGS: Nurse scientists can apply unique perspectives to increase
      understanding of injury and its consequences. Fertile areas for nursing inquiry
      include identifying people at risk, developing models to explain the association
      between risk-taking and injury, testing interventions to prevent and limit
      injury, and creating and refining interventions that are culturally relevant to
      subpopulations most at risk for injury. CONCLUSIONS: The mandate to improve
      global heath should lead to nursing inquiry about this phenomenon, including
      developing and testing interventions to prevent and reduce injury.

PMID- 17181079
TI  - Educating African pastors on mother-to-child transmission of HIV/AIDS.
AB  - PURPOSE: To educate pastors of the Assemblies of God in Burkina Faso concerning
      HIV/AIDS and mother-to-child transmission (MTCT). DESIGN: A pretest-posttest
      design was used with a convenience sample of 102 pastors attending the
      educational program on HIV/AIDS and MTCT in January, February, and March of 2005.
      The educational program was implemented in local Bible colleges in Ouagadougou,
      Burkina Faso. METHODS: Participants attended an 18-hour program on HIV/AIDS and
      MTCT. A picture booklet was designed and used to help explain the prevention of
      MTCT of HIV The pretest-posttest examination and follow-up evaluation were
      designed for this project. FINDINGS: Results of the pretest showed minimal
      knowledge of pastors regarding HIV/AIDS. The median composite scores on the
      knowledge questions increased from 16% on the pretest to 92% on the posttest.
      Within the 3-month follow-up period, 34 follow-up evaluations were received.
      Although all the responding pastors had recommended testing for expectant
      mothers, only 13 had discussed MTCT in their churches or communities.
      CONCLUSIONS: The educational program was effective in increasing the pastors'
      knowledge of HIV/AIDS and MTCT. Further research is needed to identify barriers
      to full utilization of that knowledge.

PMID- 17181080
TI  - Chronic dementing conditions, genomics, and new opportunities for nursing
      interventions.
AB  - PURPOSE: To (a) provide an overview of chronic dementing conditions; (b) discuss
      the etiologic and clinical characteristics of Alzheimer disease (AD) and
      Parkinson disease (PD) within the framework of the family systems genetic illness
      model; and (c) to explore opportunities to enhance outcomes through the
      integration of genomics information and technologies into nursing practice.
      DESIGN: An integrated review of the literature, including the organizing
      construct of the family systems genetic illness model. FINDINGS: AD and PD are
      both influenced by genetic and environmental factors; in a small percentage of
      families, gene mutations are the primary etiologic factor. Genetic testing is an
      option for some families experiencing early-onset, familial disease.
      Presymptomatic and diagnostic genetic testing have limited clinical utility for
      the more common late-onset AD and PD. CONCLUSIONS: The current abilities of
      healthcare professionals to effectively intervene in people with AD and PD are
      limited by an incomplete understanding of the biologic basis of these diseases.
      Advances in genomics research and technology are providing the information and
      tools necessary to understand the molecular basis of these devastating disorders
      toward the goal of more specific and effective interventions.

PMID- 17181081
TI  - Non-Hodgkin's lymphoma as an exemplar of the effects of genetics and genomics.
AB  - PURPOSE: To discuss the interface of genetics and genomics science in the
      identification and management of non-Hodgkin's lymphoma. The field of oncology is
      an exemplar of how the genomic revolution is influencing more individualized care
      and treatment of people with cancer and their families. DESIGN: Integrated review
      of the cancer genetics and genomics literature. METHODS: Published peer-reviewed
      research, conference proceedings, and peer-reviewed internet sites regarding the
      genetics and genomics of cancer and non-Hodgkin's lymphoma were reviewed,
      analyzed, and data synthesized. FINDINGS: All malignancies have a genetic and
      genomic basis. Genetic and genomic break-throughs are rapidly being applied to
      all aspects of cancer care including: (a) identification of at-risk individuals
      before disease occurs, (b) diagnosis and characterization of disease and its
      aggressiveness when it appears via gene expression, (c) and individualization of
      therapies over the disease course based on these new molecular technologies.
      CONCLUSIONS: Oncology nurses in every role, clinical subspecialty, and type of
      education are among the first nurses to integrate genetic and genomic information
      in such a broad context. This experience shows how genetic and genomic
      discoveries will interface with other health conditions and ultimately, will
      affect the practice of all nurses.

PMID- 17181082
TI  - Metabolic control of adults with type 2 diabetes mellitus through education and
      counseling.
AB  - PURPOSE: To test the efficacy of a controlled nursing intervention focused on
      education and counseling to improve metabolic control of adults diagnosed with
      diabetes mellitus type 2 in (DMT2) ambulatory care. DESIGN: A quasi-experimental
      design with repeated measures was selected. A sample of 45 subjects participated,
      of which 25 were in the experimental group, and 20 in the comparison group.
      Measures were taken at 0, 3, 6, 9, and 12 months, including glycosylated
      hemoglobin (HbAlc), psychosocial, and clinical variables. FINDINGS: Results
      showed a significant decrease in HbAlc in the experimental group, as well as
      positive effects of self-care agency, adaptation, and barriers to treatment (plus
      one interaction) on the HbA1c levels and on the scores of self-care actions.
      CONCLUSIONS: The counseling and educational model applied in the intervention was
      effective to improve the metabolic control of diabetic patients in the
      experimental group. Self-care agency, adaptation, and barriers were predictors of
      self-care measures and level of HbA1c.

PMID- 17181083
TI  - A cross-cultural analysis of dignified dying.
AB  - PURPOSE: To describe the characteristics of dignified dying and other terminology
      nurses used to describe this phenomenon in Ethiopia, India, Kenya, and the United
      States (US). DESIGN: A cross-sectional descriptive survey with a convenience
      sample of nurses who cared for dying patients in Ethiopia (n=14), India (n=229),
      Kenya (n=36), and the US (n=281). Data were collected between 2002 and 2004.
      METHODS: Nurses were recruited to complete the ICNP Dignified Dying survey, which
      consists of demographic information, 2 open-ended questions, and 14 questions
      about characteristics of dignified dying. FINDINGS: The 14 characteristics on the
      dignified dying scale reliably measured dignified dying, with a Cronbach's alpha
      coefficient of .91. All characteristics were rated as representative of dignified
      dying, with content validity scores ranging from .62 to .77. Factor analysis
      yielded a two-factor solution, which accounted for 53% of the variance.
      CONCLUSIONS: Findings of this study contribute to the ongoing development of the
      International Classification of Nursing Practice (ICNP) regarding the nursing
      phenomenon of dignified dying. The ICNP a unified nursing language system, is
      used to promote and facilitate scholarly exchange among nurses across countries.

PMID- 17181084
TI  - Improving cognition and function through exercise intervention in Alzheimer's
      disease.
AB  - PURPOSE: To analyze the effects of cognition on function and to explore the
      potential of aerobic exercise for promoting cognitive and functional capacities.
      DESIGN: Integrative review of literature. METHODS: Studies were selected based on
      an extensive search of electronic databases and manual cross-referencing for 1980
      to 2006, using the combination of key words: Alzheimer's disease (AD), dementia,
      or cognitive impairment with function or activities of daily living. FINDINGS:
      Three broad themes were identified from the literature analysis. First, global
      cognition has mainly been used to examine the effect of cognition on function,
      indicating an assumption that functional decline progresses in a hierarchical
      manner in AD. Second, specific cognitive domains affect functional decline in
      different ways. Executive functioning might have more effect on function than
      does memory. Third, aerobic exercise might promote cognitive and functional
      capacities in people with AD by modifying neuropathological changes in the brain.
      CONCLUSIONS: Specific cognitive domains such as executive functioning are
      important for understanding function in people with AD and are potentially
      modifiable by aerobic exercise.

PMID- 17181086
TI  - Nurses' narratives of unforgettable patient care events.
AB  - PURPOSE: To explore the experience of registered nurses (RNs) caring for patients
      in contemporary hospitals. DESIGN: The descriptive phenomenological study was
      based in the philosophical perspectives of Husserl and Merleau-Ponty. METHODS: A
      purposive sample of 46 RNs employed in acute care hospitals in the southeastern
      United States (US) were recruited by network sampling. Data from unstructured
      interviews were analyzed in an interpretive group and themes were identified.
      FINDINGS: Four themes were identified: (a) extraordinary caregiving events, (b)
      incomprehensibility, (c) questioning whether anything else could have been done,
      and (d) "alone or together," indicating the isolation nurses often experience
      while giving care as well as profound moments of connection, especially with
      patients. CONCLUSIONS: Caregiving experiences resulted in an accumulating residue
      of moral distress which in turn became ground for future experiences in the
      everyday work life of RNs. Sometimes years later, participants were still trying
      to justify and understand the outcomes and perhaps to absolve themselves from
      blame. Participants were confronted with the limits of science and skill and
      plunged into the realm of existential questions for which they had no ready
      answers.

PMID- 17181085
TI  - Psychometric evaluation of the center for epidemiological studies depression
      scale in Chinese poststroke older adults.

PMID- 17181087
TI  - Exploring the subconcepts of the Wittmann-Price theory of emancipated decision
      making in women's health care.
AB  - PURPOSE: To explore the subconcepts of the Wittmann-Price Theory of Emancipated
      Decision-Making (EDM); which is proposed as a new theoretical model for the
      nursing care of women to increase women's satisfaction with decision-making about
      healthcare issues. Infant feeding method was used as the clinical exemplar.
      DESIGN AND METHOD: A descriptive correlational design was used to test the five
      identified subconcepts of EDM (empowerment, flexible environment, personal
      knowledge, reflection, and social norms) in women's healthcare. The relationship
      of emancipated decision-making and satisfaction were explored with the Subject
      Demographic Questionnaire (SDQ), the Wittmann-Price Theory of Emancipated
      Decision-making Scale (EDMS), and the Satisfaction with Decision (SWD) scale. The
      research design was retrospective, without random sampling of subjects. Four
      research questions were posed for this investigation. Women who had uncomplicated
      deliveries and met the selected criteria were enrolled (N=97). FINDINGS: All five
      subconcepts of EDM were scored on subscales on the EDMS; flexible environment and
      personal knowledge had the highest mean scores. Pearson correlations showed that
      all five subscales were significantly related to each other except reflection
      with personal knowledge and reflection with social norms. A significant
      relationship was found between the EDM and satisfaction with the decision.
      Personal knowledge and flexible environment were the best predictors of
      satisfaction with the decision. CONCLUSIONS: The Wittmann-Price Theory of EDM is
      a theoretical model with implications for nursing care of women who are involved
      in a healthcare decision, such as choice of infant feeding. Further studies are
      needed to determine the importance of each of the subconcepts in relation to
      emancipated decision-making.

PMID- 17181088
TI  - Testing a questionnaire to measure asthma-related quality of life among children.

PMID- 17181089
TI  - Cross-cultural reliability of the Health Perception Index and the Health Control
      and Competence Index.
AB  - PURPOSE: To test the reliability of two Spanish instruments to measure (a) health
      perceptions, and (b) health control and competence. DESIGN: Triangulated
      methodology used with two different Latino populations. METHODS: Preliminary
      qualitative data were collected in Mexico. Based on themes from Mexico, data were
      collected from 44 men (Dominican Republic, n=24 ; Peru, n=20) with two
      instruments, the Health Competence and Control Index and the Health Perception
      Index. Alpha reliability estimates were obtained. FINDINGS: Results of the study
      confirmed reliability of the instruments in one of the Latino populations,
      consistent with understanding of the constructs found in the Mexican study.
      Reliability was low in the second Latino population. CONCLUSIONS: Although
      results from this study are useful, further translation and research procedures
      are needed to address the many differences among ethnically similar groups and to
      further strengthen internal and external validity of instruments designed to
      assess Latino men's perceptions of health and their control over health.

PMID- 17181090
TI  - Barriers to nurses' reporting of medication administration errors in Taiwan.
AB  - PURPOSE: To describe nurses' perceptions of reporting barriers to reporting
      medication administration errors (MAE) and to examine the relationship between
      the barriers to MAE reporting and cultural factors and nursing work environment
      in Taiwan. METHODS: A cross-sectional, descriptive correlational design with self
      administered questionnaires was conducted in one large medical center hospital in
      southern Taiwan. The measurement tools included the Chinese versions of the Work
      Environment Questionnaire, Barriers to MAE Reporting, Index of Hierarchy of
      Authority, and Face-Concern scale. A mail survey of 807 nurses using the Total
      Design Method was implemented for data collection with 597 questionnaires used in
      data analyses. FINDINGS: The major perceived barrier was fear. Regression
      analysis showed that power hierarchy, face-saving concern, and work environment
      factors (e.g., quality management and peer relations) accounted for 54.6%
      variance in the barriers. Age, educational background, working experience,
      experience of having made MAEs, and failure to report MAEs were not associated
      with the barriers. CONCLUSIONS: Taiwanese nurses perceived similar barriers to
      MAE reporting. The more power hierarchy and face-saving concern the nurses agreed
      on, the more barriers they perceived. The association between the barriers and
      nursing work environment was negative and weak.

PMID- 17181091
TI  - Sexual harassment of female nurses by patients in Japan.
AB  - PURPOSE: To determine the prevalence and details of sexual harassment of female
      nurses by patients and nurses' reactions in Japanese hospitals. METHODS: A
      research survey with a self-administered questionnaire was conducted.
      Questionnaires were distributed to hospital nurses, and 473 of 600 (78.8%)
      questionnaires were returned. A content analysis was done with descriptive data
      from the questionnaires. FINDINGS: The proportion of female nurses who have ever
      been sexually harassed by patients was 55.8%. Sexual harassment was prevalent in
      the hospital environment and some details were serious. Conversely, nurses tended
      to react passively and moderately and, in many cases, they did not attempt to
      stop the patients. Relatively few incidents were reported to the appropriate
      supervisors. CONCLUSIONS: This sample of Japanese hospital nurses were at high
      risk for sexual harassment, and administrators tended to underestimate the
      problem. No effective policies to combat this situation have yet been established
      in Japanese hospitals.

PMID- 17181092
TI  - Study of nasal cycles in children by acoustic rhinometry.
AB  - BACKGROUND: Studies concerning nasal cycle physiology in children are still rare,
      and controversies exist about its existence. This study was ascertained to
      evaluate the dynamic behavior of inferior turbinates in children by acoustic
      rhinometry. METHODS: Sixteen volunteer patients, aged 2-11 years old (mean, 6.25
      years), were evaluated between April and July 2003. The patients submitted to
      periodic acoustic rhinometry, with triplicate measurements (each 30 minutes) for
      3 hours. RESULTS: All evaluated children presented nasal cycles, with five
      children presenting a classic pattern (31.25%), three children presenting a
      concert pattern (18.75%), and eight children presenting an irregular pattern
      (50%). CONCLUSION: This study suggests that children present nasal cycles, as
      well as adults. Nevertheless, the most prevalent pattern in children was the
      irregular pattern, whereas in adults the most frequently detected is the classic
      pattern.

PMID- 17181093
TI  - Topical steroid drops for the treatment of sinus ostia stenosis in the
      postoperative period.
AB  - BACKGROUND: Chronic oral steroid use causes significant morbidity, including
      osteoporosis, immunosuppression, and adrenal insufficiency. Refractory chronic
      rhinosinusitis patients often take repeated oral steroid courses to treat
      polypoid disease or sinus ostia stenosis. This study evaluated topical steroid
      drop efficacy in treating recurrent sinus ostia stenosis in the postoperative
      period. METHODS: The 5-year single institution experience with topical steroid
      drop use after endoscopic sinus surgery (ESS) was evaluated by retrospective
      review. Patients were included if they began topical dexamethasone ophthalmic,
      prednisolone ophthalmic, or ciprofloxacin/ dexamethasone otic intranasally (used
      off-label) within 3 months after ESS. Outcomes (i.e., ostia patency, oral steroid
      use, revision surgery, and complications) were assessed for a 6-month period
      after steroid drop initiation. RESULTS: Thirty-six patients met inclusion
      criteria. Forty-four surgeries were performed during the study period; 67 sides
      were treated postoperatively with topical steroid drops. In 86.6% of cases,
      steroid drops were used to treat frontal ostium stenosis or frontal recess edema;
      93.2% of surgeries were revision procedures. Sixty-four percent of sinuses were
      treated successfully with topical steroid drops, 14.9% remained stable, and 20.9%
      failed. Reasons for failure included persistent/worsening edema, scarring, or
      noncompliance. Ten patients (27.8%) required oral steroids and 4 patients (6%)
      underwent revision surgery during the study period. One case of adrenal
      suppression occurred. CONCLUSION: Topical steroid drops are beneficial in
      preventing sinus ostia stenosis in the postoperative period and may decrease the
      propensity toward repeated oral steroid therapy. This is particularly noteworthy
      in this challenging cohort, largely composed of revision frontal sinus surgery
      patients.

PMID- 17181094
TI  - An assessment of sinus quality of life and pulmonary function in children with
      cystic fibrosis.
AB  - BACKGROUND: Treatment of patents with cystic fibrosis (CF) is primarily directed
      at the lungs. However, there is a growing feeling that the status of the sinuses
      may have a profound influence on the status of the lungs in these patients. A
      number of investigators have demonstrated a relationship among coexisting
      rhinitis, sinusitis, other upper airway conditions, and lung disease. Several
      studies have shown that treatment and resolution of sinusitis results in an
      improvement in a number of pulmonary conditions. We hypothesize that pulmonary
      function test scores will be lower in patients with CF with more severe
      sinusitis. METHODS: Consecutive CF patients were asked to complete a sinus
      specific quality-of-life instrument, the 16-item Sino-Nasal Outcome Test (SNOT
      16), and these scores, were compared to FEV, scores. RESULTS: Univariate analysis
      revealed a significant correlation between SNOT-16 and FEV1 in patients under the
      age of 12. There was a trend toward significance in the older children and
      evaluation of the raw data shows that children with the highest FEV, had the
      lowest SNOT-16. CONCLUSION: This study indicates that the severity of sinus
      disease correlates with the severity of pulmonary disease in CF patients under
      the age of 12. We plan to use the SNOT-16 to assess sinus interventions on
      pulmonary status.

PMID- 17181096
TI  - Brain perfusion single photon emission computed tomography findings in patients
      with posttraumatic anosmia and comparison with radiological imaging.
AB  - BACKGROUND: Different techniques in neuroimaging have been proposed for
      assessment of olfactory dysfunction but they are not without limitations.
      Recently, some studies showed the usefulness of single photon emission-computed
      tomography (SPECT) in evaluation of patients with posttraumatic anosmia. This
      study was designed to assess the possible diagnostic value of SPECT findings in
      patients with posttraumatic anosmia in comparison with magnetic resonance imaging
      (MRI)/CT imaging. METHODS: Sixteen patients who had head trauma and consequently
      anosmia, which was defined according to Cain's identification test, were included
      in this study. Two nonanosmic groups, traumatic patients and nontraumatic healthy
      individuals, were selected as control groups for this study. Qualitative and
      semiquantitative brain perfusion SPECT was performed by measuring the uptake
      ratio of the orbital frontal cortex to occipital pole in the sagittal projections
      (uptake index). All 16 target patients had a previous CT scan and/or MRI.
      Semiquantitative and qualitative brain perfusion SPECT were compared with
      radiological imaging. RESULTS: Semiquantitative assessment of brain perfusion
      SPECT revealed remarkable orbital frontal hypoperfusion as compared with two
      control groups. 87.5% of anosmic patients showed orbital frontal hypoperfusion (
      2 SD below the lowest level in healthy controls). In addition, the
      semiquantitative SPECT method detected more orbitofrontal abnormality than the
      qualitative method or radiological imaging (MRI and/or CT). CONCLUSION: Findings
      suggest that by using SPECT, posttraumatic anosmia corresponds to the
      hypoperfusion in the orbital frontal cortex in a great number of patients.
      Because of its availability, rather low cost, technical ease, and possibility to
      obtain objective quantitative information, brain perfusion SPECT can be
      complementary to other diagnostic techniques in the evaluation of olfactory
      function, although additional neurophysiological and imaging studies are needed.

PMID- 17181095
TI  - Medical and surgical considerations in patients with Samter's triad.
AB  - BACKGROUND: The aim of this study was to report on objective and subjective
      outcomes of patients with Samter's triad (ST) treated with functional endoscopic
      sinus surgery (FESS), and correlate these results with aspirin desensitization
      (DS) in patients. METHODS: We performed a retrospective analysis of prospectively
      collected data in 15 patients requiring revision FESS after failing maximum
      medical therapy and prior sinus surgery for chronic rhinosinusitis in the context
      of ST. Five patients underwent aspirin DS and 10 patients did not (non-DS). These
      patients represent a subset of patients previously reported who were treated in a
      tertiary rhinology setting over a 3-year period (1999-2001). CT scans were graded
      according to the Lund-Mackay grading scale and symptom scores were assessed using
      the Sino-Nasal Outcome Test (SNOT-20). Endoscopy was scored according to the
      Rhinosinusitis Task Force methodology. All patients had a minimum 2-year follow
      up. RESULTS: Preoperative CT scores were 20.1+/-1.9 for non-DS patients and
      20.4+/-2.0 for DS patients (p = NS). Preoperative and postoperative SNOT-20
      scores for non-DS patients were 31.8+/-3.9 and 8.8+/-1.7, respectively, as
      compared with 32.0 z 3.6 and 7.3 +/-1.7 for DS patients (p = NS). Preoperative
      and postoperative endoscopy scores for non-DS patients were 7.6+/-1.2 and 2.0+/
      0.4, respectively, as compared with 7.6 +/-1.3 and 1.1+/-0.4 for DS patients (p =
      NS). Of DS patients, none required additional surgery whereas 8 of 10 non-DS
      patients required additional revision during the follow-up period (p = 0.003).
      CONCLUSION: Revision FESS benefits patients with ST; however, the addition of
      aspirin DS decreases the likelihood that patients with ST will require additional
      surgical intervention over a 2-year period.

PMID- 17181097
TI  - Invasive fungal rhinosinusitis: what is the appropriate follow-up?
AB  - BACKGROUND: Early detection and aggressive surgical and medical management have
      been associated with higher overall survival rates among patients with invasive
      fungal rhinosinusitis (IFS). With improved survival comes the question of how to
      appropriately manage these patients once disease stability has been achieved.
      Previous reports suggest follow-up only as long as the patients remain
      immunocompromised. This study attempts to answer the question of long-term
      clinical follow-up and suggests a regimen suitable for ensuring minimal
      posttreatment complications. METHODS: A retrospective review included all
      patients diagnosed with IFS between 1988 and 2004. The study group included
      patients who survived the initial treatment course, with at least 30 days of
      posttreatment follow-up of their IFS. Patient records were reviewed for
      significant complications, evidence of chronic sinus disease, the clinical status
      of their underlying medical comorbidities, and frequency and mode of follow-up.
      RESULTS: Thirteen patients were included. The average follow-up time was 633
      days. Significant complications included one patient with acute bacterial
      sinusitis with resultant visual loss and one patient with chronic osteomyelitis
      of the orbit and skull base. Six of 13 patients had persistent chronic bacterial
      rhinosinusitis with crusting and bone sequestration. All complications were noted
      to occur after initial IFS eradication was thought to have taken place.
      CONCLUSION: Significant complications of IFS can occur after medical remission
      and recovery of immune competence. Patients with IFS should be followed long term
      until remucosalization of the sinuses, resolution of crusting, and cessation of
      bony sequestration has occurred.

PMID- 17181098
TI  - Respiratory epithelial adenomatoid hamartomas and chondroosseous respiratory
      epithelial hamartomas of the sinonasal tract: a case series and literature
      review.
AB  - BACKGROUND: Respiratory epithelial adenomatoid hamartomas (REAH) and
      chondroosseous respiratory epithelial (CORE) hamartomas are rare
      sinonasal/nasopharyngeal lesions first characterized in 1995. Although REAH and
      CORE hamartomas are benign, nonneoplastic lesions, awareness and recognition of
      these lesions are important because they can be confused grossly and
      microscopically with more threatening sinonasal tumors. METHODS: This report
      presents two cases of REAH and one case of a CORE hamartoma. The literature
      regarding REAH and CORE hamartomas is reviewed, and their distinction from
      related entities of the sinonasal tract and nasopharynx is discussed.
      CONCLUSIONS: Misdiagnosing REAH or CORE hamartoma as either inverted papilloma or
      adenocarcinoma may lead to far more aggressive surgical intervention then is
      necessary.

PMID- 17181099
TI  - The role of mitomycin C in surgery of the frontonasal recess: a prospective open
      pilot study.
AB  - BACKGROUND: Mitomycin C (MMC) inhibits fibroblast proliferation. The objective of
      this study was to determine the efficacy of MMC in reducing frontal ostium
      stenosis after endoscopic sinus surgery. METHODS: A prospective open pilot study
      was conducted in 28 patients who had undergone one or more previous surgical
      interventions for frontal sinusitis. MMC solution was applied to the frontal
      ostial region via an endoscopic or combined endoscopic and external approach.
      Patency of the frontal ostium was evaluated endoscopically during regular follow
      up. If restenosis was observed further, endoscopic application of MMC was
      undertaken. RESULTS: There were 17 men and 11 women (mean age, 51.7 years; range,
      26-86 years). Mean number of applications was 1.5 (range, 1:3). Mean follow-up
      was 19 months (range, 6-32 months). Patency rate was 86%. CONCLUSION: Mitomycin
      appears to have an important role in reducing postoperative scarring, which may
      obviate the need for repeated and more extensive surgery.

PMID- 17181100
TI  - Long-term effect of stenting after an endoscopic modified Lothrop procedure.
AB  - BACKGROUND: The aim of this study was to study the effect of stenting with a
      silastic sheet on the long-term patency of the common frontal ostium after an
      endoscopic modified Lothrop procedure (EMLP). METHODS: A retrospective analysis
      was performed of prospectively collected data at an academic tertiary referral
      center, where 72 patients underwent an EMLP between 1996 and 2003. Patency of the
      common frontal ostium was studied as an ordinal variable with three classes
      (patent, stenotic, and closed). RESULTS: A common ostium was endoscopically
      visualized in 94% of the patients (61.1% patent and 33.3% stenotic). Symptoms
      improved in 75% of the patients. A significant positive correlation was found
      between ostium patency and symptom improvement. Twenty-five patients were stented
      postoperatively. There was no statistical difference between the stented and the
      nonstented groups with regards to ostium patency and symptoms improvement.
      CONCLUSION: Short-term stenting does not appear to reduce the rate of
      postoperative stenosis of the common frontal ostium after an EMLP.

PMID- 17181101
TI  - Silicone tubing after endoscopic dacryocystorhinostomy: is it necessary?
AB  - BACKGROUND: Endoscopic dacryocystorhinostomy (EN-DCR) is increasing in popularity
      as a treatment of nasolacrimal obstructions because it has proven to be an
      effective and safe procedure. In this study the success of EN-DCR combined with
      or without bicanalicular silicone stents was evaluated in patients with
      nasolacrimal obstructions. METHODS: Forty-two consecutive EN-DCR procedures were
      performed in 36 patients during 2000-2004. The surgery was primary in 23 cases
      and revision in 19 cases. Bicanalicular silicone stents were inserted in 18 cases
      and in 24 cases stenting was avoided. RESULTS: The overall success rate after EN
      DCR was 81%. The success rate of EN-DCR was 89% with silicone tubing and 75%
      without silicone tubing. The mean duration of postoperative follow-up was 4
      months. CONCLUSION: In our retrospective study no significant statistical
      differences were seen between the patients with stenting compared with patients
      without stenting. However, prospective, randomized studies are clearly needed to
      answer the question of whether the use of stents is advisable.

PMID- 17181102
TI  - High-resolution computed tomography analysis of the greater palatine canal.
AB  - BACKGROUND: The greater palatine foramen injection is effective for minimizing
      bleeding during sinus surgery. The correct depth is important to minimize risk of
      orbital penetration. This study analyzed the length of the greater palatine canal
      using high-resolution computed tomography (HRCT). METHODS: HRCT sinus scans from
      100 adults were analyzed. One thousand two hundred measurements were performed by
      three observers. RESULTS: The mean distance of the greater palatine foramen to
      the orbital floor was 40+/-3 mm in men and 37+/-3 mm in women (range, 32-46 mm).
      The mean distance of the greater palatine foramen to the sphenopalatine foramen
      was 28+/-2 mm in men and 27+/-2 mm in women (range, 23-33 mm). CONCLUSION: The
      greater palatine foramen injection is an appropriate method to minimize bleeding
      during endoscopic sinus surgery. The authors recommend an injection depth of 25
      mm in adults to minimize the risk of intraorbital complications.

PMID- 17181103
TI  - Key maneuvers for successful correction of a deviated nose in Asians.
AB  - BACKGROUND: The authors present surgical results of 64 Asian patients with
      deviated nose and introduce important key maneuvers used in the surgery. METHODS:
      Sixty-four consecutive patients who underwent corrective rhinoplasty because of a
      deviated nose were analyzed retrospectively. Approaches and techniques used for
      the surgery, surgical results, and complications were evaluated. A questionnaire
      was used to evaluate each patient's functional and esthetic satisfaction.
      Preoperative and postoperative standardized photographs of the face were
      evaluated to judge objectively the esthetic outcomes of the surgery. RESULTS: An
      endonasal approach was used in 44 patients and an open approach was used in 20
      patients. Five important key maneuvers to correct the deviation were noted, in
      the order of frequency: septoplasty, osteotomy, spreader graft, turbinoplasty,
      and camouflage graft. Additional procedures included augmentation of the dorsum,
      tip surgery, and hump removal. On a 5-point box scale of 0-4, the patients scored
      their satisfaction on functional improvements as 3.2+/-0.79 and their esthetic
      satisfaction as 3.0+/-0.8. The objective evaluation of the appearance showed
      complete correction in 84.4%, a minimally visible deviation in 10.9%, and a
      residual deviation but less than before surgery in 4.7%. Aside from residual
      deviations, complications included a slight depression of the middorsum after
      spreader graft and a malpositioning of the dorsal cartilage graft. CONCLUSION:
      Deviated nose in Asians can be managed successfully by combining key maneuvers
      that correct specific anatomic abnormalities. Many of these key maneuvers require
      modifications that take into account the race-specific characteristics of the
      Asian nose.

PMID- 17181104
TI  - A multicenter evaluation of the safety of Gore-Tex as an implant in Asian
      rhinoplasty.
AB  - BACKGROUND: A retrospective multicenter study examined the safety of Gore-Tex as
      a nasal implant in rhinoplasty. METHODS: This study involved 853 patients (656
      primary surgeries and 197 secondary surgeries) who had undergone rhinoplasty and
      used Gore-Tex either at the dorsum or at the nasal tip. Data were extracted from
      the medical records by surgeons and entered on a standard form. Data included the
      information about the demographics and history of the patient, method and results
      of surgery, complications, follow-up, and various factors believed to predispose
      to complications. RESULTS: The average follow-up period was 18 months. Overall
      complication rate associated with Gore-Tex was 2.5% (21 cases). Infection was the
      most common complication (18 cases; 2.1%) followed by two cases of seroma and one
      case of persistent nasal swelling. Among the 21 suffering complications, 19
      patients (91%) needed graft removal. Nine cases of infection developed in primary
      surgeries (1.4%) and nine cases developed in secondary surgeries (4.6%), which
      represented a statistically higher complication rate in those undergoing
      secondary surgery (p = 0.0062). Infections developed within 1 month in five cases
      and nine cases developed infection >6 months postoperatively. Other complications
      including esthetic problems were identified in 16 cases (1.9%). CONCLUSION: Gore
      Tex should be used judiciously in rhinoplasty because of a 2.1% infection rate, a
      risk that is higher still after secondary surgery; moreover, once infected, Gore
      Tex implants usually require removal.

PMID- 17181105
TI  - The role of accompanying sinonasal abnormalities in the outcome of endonasal
      dacryocystorhinostomy.
AB  - BACKGROUND: Acquired nasolacrimal duct obstruction may occur simultaneously and
      possibly as a consequence of sinonasal disease, because the nasolacrimal system
      is anatomically related to important nasal and sinus structures. METHODS: Thirty
      seven patients with nasolacrimal canal obstruction (42 eyes) were evaluated with
      paranasal sinus computerized tomography (CT) to determine the presence of
      sinonasal abnormalities if any. All of the patients underwent endoscopic
      dacryocystorhinostomy (end-DCR) and accompanying sinonasal pathology was treated
      also in the same session. RESULTS: Paranasal sinus CT examinations revealed one
      or more sinonasal abnormalities in 26 (73.3%) patients. The postoperative success
      rate of end-DCR procedure in patients with sinonasal abnormalities was 82.8%,
      whereas this figure increased to 92.3% in patients without additional sinonasal
      disease. However, additional rhinological surgery did not affect the success rate
      of end-DCR procedure significantly (p = 0.640). CONCLUSION: These data establish
      a positive correlation between sinonasal abnormalities and the presence of
      nasolacrimal outflow obstruction, but the additional rhinological surgery does
      not significantly affect the results of the end-DCR procedure.

PMID- 17181106
TI  - The relationship between atopy and chronic rhinosinusitis.
AB  - BACKGROUND: The aim of this study was to determine whether atopy influences
      either clinical and radiological severity or surgical revision rates in patients
      with chronic rhinosinusitis (CRS). METHODS: Patients who had been scheduled for
      endoscopic sinus surgery were classified as having CRS or nasal polyposis. Their
      atopic status was determined by ImmunoCAP testing. Disease severity was assessed
      clinically by the Lund symptom and Sino-Nasal Outcome Test 20 (SNOT-20) quality
      of-life scores and radiologically by the Lund-Mackay CT score. RESULTS: One
      hundred ninety-three consecutive patients with rhinosinusitis were included in
      the study. The prevalence of atopy in this group was found to be 30%. No
      association was found between atopic status and Lund symptom scores. Analysis of
      the SNOT-20 scores indicated that atopic patients had higher sneezing scores (p <
      0.03), reduced productivity (p < 0.01), and reduced concentration (p < 0.01). The
      mean CT score was significantly higher in the atopic patients than in nonatopic
      patients overall (14.2+/-1.6 versus 12.2+/-1.3; p = 0.05), although within each
      of the clinical subgroups no statistically significant relationship was observed
      between a patients' atopic status and their CT scores. The rate of revision
      surgery was not significantly different between atopic and nonatopic patients.
      CONCLUSION: These results suggest that atopic status has minimal impact on the
      severity of CRS.

PMID- 17181107
TI  - The up-regulated expression of tenascin C in human nasal polyp tissues is related
      to eosinophil-derived transforming growth factor beta1.
AB  - BACKGROUND: Tissue remodeling is an important characteristic of nasal polyps
      (NPs). However, the mechanisms underlying the remodeling processes are poorly
      defined. This study investigated the role of transforming growth factor (TGF)
      beta1 and eosinophils in the expression of tenascin C (Tn-C), an extracellular
      matrix glycoprotein, in NPs. METHODS: The protein expression of Tn-C and TGF
      beta1 was examined by means of immunohistochemistry in NPs and normal control
      inferior turbinate tissues. Furthermore, cell culture, quantitative RT-PCR, and
      in situ immunocytofluorescence techniques were used to investigate the direct
      effect of TGF-beta1 and eosinophils on Tn-C production in primary nasal
      epithelial cells. RESULTS: Tn-C protein expression was significantly up-regulated
      in NP tissues and correlated with TGF-beta1+ eosinophils. TGF-beta1 and
      eosinophils dramatically induced Tn-C mRNA and protein expression in nasal
      epithelial cells. The effect of eosinophils could be inhibited partly by a
      neutralizing antibody to TGF-beta1. CONCLUSION: Eosinophil-derived TGF-beta1 may
      contribute, at least in part, to the tissue remodeling in NPs.

PMID- 17181108
TI  - Detection of rhinovirus in turbinate epithelial cells of chronic sinusitis.
AB  - BACKGROUND: In contrast to the well-established association of rhinovirus (RV)
      with acute sinusitis, little is known about the role of RV infections in the
      pathogenesis of chronic sinusitis. Therefore, we assayed the nasal cavity mucosae
      of chronic sinusitis patients lacking signs of acute viral infection for the
      presence of RV. METHODS: Nasal lavage fluids and turbinate epithelial cells from
      39 sinusitis patients and 27 control subjects were tested. Turbinate epithelial
      cells were collected using a Rhino-probe mucosal curette. Picornavirus was
      assayed by an initial reverse-transcription polymerase chain reaction (PCR), and
      picornavirus-positive samples were assayed by nested reverse-transcription PCR to
      detect RV. RESULTS: All lavage fluids from both groups, as well as control
      epithelial cells, were negative for picornavirus. In contrast, 8 of 39 (21%)
      epithelial cell samples from sinusitis patients were positive for picornavirus.
      RV-specific nested-PCR revealed that all eight of these samples were positive for
      RV. CONCLUSION: The detection of RV in the turbinate epithelial cells of chronic
      sinusitis patients suggests that RV may be important in the pathogenesis of
      chronic sinusitis.

PMID- 17181109
TI  - Do nasal polyps and inverted papilloma have similar disorders in cell cycle
      regulation?
AB  - BACKGROUND: The aim of this study was to determine the expression of cell cycle
      regulation genes in patients with inverted papilloma (IP) and compare this with
      expression in patients with nasal polyps (NPs). METHODS: Tissue from 18 patients
      with IP and 5 patients with NPs were stained by immunohistochemistry techniques
      for p53 and p27. Measurement of the gene expression was performed by three
      assessors, who we blinded with respect to the specimens. RESULTS: The mean score
      for p53 expression (3.33) was significantly higher in the IP group than the NP
      group (1.46). The mean difference between IP and NPs was 1.80 (CI, 1.15-2.46; p =
      0.003). Additionally, we showed in a number of individuals variation in the p53
      expression within the same specimen. There was no difference in the mean scores
      for p27, with the mean difference 0.79 (CI, 0.30-1.89; p = 0.147). CONCLUSION:
      Our study established a significantly increased expression of p53 in IP when
      compared with NPs. Additionally, there appear to be two different cell
      populations identified within the same specimens, which exhibited variation in
      their p53 expression.

PMID- 17181111
TI  - Polymorphism at the glutathione S-transferase P1 locus in Korean patients with
      perennial allergic rhinitis.
AB  - BACKGROUND: Oxidative stresses, which induce the reactive oxygen species (ROS),
      can cause airway inflammation. The glutathione S-transferases (GSTs) protect
      cells against the effects of ROS. GSTP1 polymorphism may have some effect on
      allergic rhinitis. Therefore, we have compared the effects of GSTP1 polymorphisms
      on the perennial allergic rhinitis in Koreans. METHODS: Patients with perennial
      allergies (149 patients) were selected. The control group included 156 healthy
      people. Genotypes were evaluated via polymerase chain reaction and restriction
      fragment length polymorphism, using the Alw26I restriction enzyme. RESULTS: There
      was no significant difference between groups in the proportions of the Ile/Ile
      (wild type) and Ile/Val (heterozygote) genotypes. However, the Val/Val (mutant
      type homozygote) was expressed in only one case (0.7%) in the perennial allergic
      rhinitis group, as compared with 11 cases (7.1%) in the controls (p < 0.05).
      CONCLUSION: Our results indicate that the Val/Val genetic polymorphism of GSTP1
      may exert some protective effects in allergic inflammation.

PMID- 17181110
TI  - Role of FEF25-75 as an early marker of bronchial impairment in patients with
      seasonal allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis may be associated with asthma. Forced expiratory
      flow between 25 and 75% of vital capacity (FEF2575) is a measure of small airways
      narrowing. The aim of this study was to evaluate whether patients with seasonal
      allergic rhinitis (SAR) without symptoms of asthma might, nevertheless, have
      airways obstruction both in and out of the pollen season. METHODS: Fifty patients
      (mean age, 23.7+/-4.9 years) with SAR were evaluated both during and outside the
      pollen season. All of them had moderate-severe grade of nasal obstruction. Total
      symptom score, rhinomanometry, nasal lavage, nasal scraping, spirometry, and
      methacholine (MCH) bronchial challenge were assessed in all subjects. RESULTS:
      Although data on forced vital capacity and response to MCH were similar in and
      out of the pollen season, all other parameters were markedly different. The major
      finding of the study was that FEF25-75 was significantly associated with nearly
      all of the parameters considered, including bronchial hyperreactivity, with
      Pearson R ranging from 31 to 75% and differences in mean FEF25-75 ranging between
      14.5 and 16.5% of predicted. The more significant association was with nasal
      airflow in the pollen season (R = 82.8%; p < 0.001). A significant association
      persisted for all parameters while controlling for season. CONCLUSION: This study
      highlights the link between upper and lower airways and the role of FEF25-75 as
      an early marker of bronchial impairment in those patients with SAR alone.

PMID- 17181112
TI  - Differential effects of insulin-like growth factors on scratch wound repair in
      respiratory epithelial cells.
AB  - BACKGROUND: Insulin-like growth factors (IGFs) I and II, being potent promoters
      of cellular growth and differentiation, were investigated for their effectiveness
      in improving the rate of scratch closure in human respiratory epithelium in
      vitro. METHODS: Human epithelial cell lines from the nasal, bronchial, and
      tracheal regions were analyzed for their response to IGF-I and IGF-II, in a
      confluent monolayer scratch assay. IGF-binding proteins (IGFBPs) produced by
      certain cells are able to reduce the effectiveness of the IGFs. Consequently, the
      analogues LongR3 IGF-I, Des1-3 IGF-I and Arg3 IGF-I were investigated also
      because of their lower affinity for the IGFBPs, while still retaining unaffected
      affinity for the IGF-I receptor. RESULTS: All growth factors that were analyzed
      significantly improved the rate of scratch closure in bronchial and tracheal
      epithelial cells (p < or = 0.05). In comparison, scratch closure was markedly
      slower in nasal epithelial cells and IGF-I was the most effective growth factor
      at effecting scratch closure in these cells. The IGF-I analogues did not
      significantly improve scratch closure compared with IGF-I, despite the presence
      of IGFBP-3 in nasal, bronchial, and tracheal epithelial cells. CONCLUSION:
      Addition of IGF-I to wounded nasal epithelial cells increases the rate of scratch
      closure and therefore may have potential for improving the healing of the nasal
      mucosa.

PMID- 17181113
TI  - Making the call: the diagnosis of acute community-acquired bacterial sinusitis.
AB  - BACKGROUND: Although one of the most common illnesses encountered in the primary
      care setting, acute community-acquired bacterial sinusitis (ACABS) can be a
      challenge to diagnose. METHODS: Existing diagnostic modalities ranging from
      clinical history to imaging studies used to diagnose ACABS are discussed.
      RESULTS: Numerous methods exist but they do not distinguish well between viral
      and bacterial illness. CONCLUSION: Diagnosis of ACABS should primarily be made
      based on the clinical history. Other modalities provide useful information in
      select cases.

PMID- 17181114
TI  - Therapeutic choices in the treatment of acute community-acquired bacterial
      rhinosinusitis.
AB  - BACKGROUND: Acute bacterial rhinosinusitis (ABRS) is a common medical problem
      affecting a large percentage of the population. The disease will most often
      follow a viral upper respiratory tract infection. METHODS: Appropriately
      diagnosed, ABRS is best treated with antibiotics, but other medications may play
      a role in some circumstances. Increasing antibiotic resistance to the common
      bacteria causing ABRS has occurred in the past 20 years, driven largely by
      inappropriate or unnecessary antibiotic use. RESULTS: There are many antibiotics
      available that may be used for the treatment of ABRS. The selection of the best
      antibiotic option is determined by evaluating a number of factors, with the
      potential antibiotic resistance being an important consideration. CONCLUSION:
      This article reviews current recommendations for the antibiotic treatment of
      ABRS.

PMID- 17181115
TI  - Antimicrobial resistance: current status and future direction.
AB  - BACKGROUND: Antimicrobial resistance is initiated through mutations in bacterial
      genes, culminating in end products that help circumvent the action of specific
      antimicrobial agents. Resistant mutants can proliferate under a number of
      circumstances but primarily through the action of selective pressure from the
      overuse of antimicrobial agents. METHODS: The results of surveillance studies
      over approximately the last ten years were evaluated. CONCLUSION: Resistance
      rates in the group of microorganisms associated with respiratory tract infections
      had been increasing rapidly over the past 10 years, but, recently, many seem to
      have reached a plateau. However, newer, more invasive clones of methicillin
      resistant Staphylococcus aureus (MRSA), differing from health care-associated
      MRSA (HA-MRSA), and typically associated with community-acquisition (CA-MRSA),
      recently have begun to proliferate. Burgeoning use of fluoroquinolones has
      impacted the Gram-negative bacilli (e.g., Pseudomonas aeruginosa, Escherichia
      coli, and Salmonella), causing their resistance rates to approach the critical
      point. A better understanding of the epidemiology of resistance and responsible
      use of antimicrobial agents are mandatory if the continuing rates of increasing
      resistance are to be abrogated.

PMID- 17181117
TI  - MVP targets chronically ill Medicaid recipients.

PMID- 17181116
TI  - Retraction: duplicate article.

PMID- 17181118
TI  - Nonadherence to beta blockers is a big issue with patients post-MI.
AB  - Although healthcare organizations have made great strides in boosting prescribing
      rates for beta blockers in patients who have suffered a myocardial infarction,
      (MI) data show that patients are not reaping the full value from these life
      saving drugs. The problem is poor medication compliance. Experts maintain that
      providers and healthcare organizations should now turn their attention to this
      pressing problem.

PMID- 17181119
TI  - North Carolina initiative targets CVD and diabetes with telehealth intervention.
AB  - Disadvantaged populations are adversely affected by chronic disease, but they are
      among the toughest to reach with preventive care. However, the innovators behind
      a bold initiative in North Carolina are hoping that a telehealth intervention can
      bridge at least some of these gaps in care and possibly even change the course of
      chronic disease in schoolchildren.

PMID- 17181120
TI  - New scoring system helps providers assess risk in bariatric surgery candidates.
AB  - Two-thirds of American adults are obese, and conservative approaches to the
      problem are not working in many of these cases. However, it is not entirely clear
      when providers should recommend bariatric surgery. To help providers better guide
      their patients, investigators at Duke University in Durham, NC, have unveiled a
      simple risk-scoring system that stratifies patients into low-, medium-, and high
      risk categories. The approach needs further validation, but investigators believe
      they have presented enough data to have a positive effect on informed consent.

PMID- 17181121
TI  - United States Government Accountability Office (GAO) targets laboratory quality.

PMID- 17181122
TI  - The rule of law and bioterrorism.
AB  - Bioterrorism is multi-faceted. Its impact will extend beyond the victims, the
      agent used, and the perpetrator(s). The rule of law must be considered in the
      wake of September 11 and the fall 2001 anthrax attacks. Bioterrorism preparedness
      should address rule of law and social issues. Laboratory professionals must be
      prepared for professional, civil justice, and social impact in the event of a
      future major bioweapons event.

PMID- 17181123
TI  - Diego(a) antigen frequency and anti-Diego(a) frequency in a South Texas
      community.
AB  - OBJECTIVE: The objective of this study was to determine the percent of the donor
      population in a South Texas community positive for the red cell antigen Diego(a)
      (Di(a)) and to determine the percent of anti-Di(a) in previously transfused
      patients. DESIGN: Donor segments from 270 type A and type O donors were typed
      with anti-Di(a) and 305 previously transfused patients were screened for anti
      Di(a). SETTING: The study was conducted using donor segments from units collected
      by the South Texas Blood Center and blood samples from patients in three
      hospitals in Corpus Christi TX. PATIENTS OR OTHER PARTICIPANTS: The typing serum
      was from a type A donor, so only A and O donors were used for the antigen typing.
      The sera used for the antibody screens were from patients with previous
      transfusions in the local hospitals. Duplicate samples were eliminated. RESULTS:
      Of the 270 type A and O donors, seven (2.6%) were found to be Di(a) positive and
      four (1.3%) of the 305 previously transfused patients had anti-Di(a).
      CONCLUSIONS: In 1985, red blood cell antigen typing of Mexican American blood
      donors in the Corpus Christi area revealed a Di(a) antigen frequency of 14.7%
      with eight percent in Mexican American blood donors from two other areas of
      Texas. With an Hispanic population of 50.4%, it was expected that four percent to
      seven percent of the donor population would be positive for the antigen. The
      finding of only 2.6% Di(a) positive donors demonstrates about a 20% Mexican
      American donor population. Anti-Di(a) was found in 1.3% of the plasma samples
      from previously transfused patients. These results would indicate a 0.03% to
      0.05% transfusion incompatibility in patients with a negative antibody screen for
      the Corpus Christi area. Areas of the United States with a higher percent Mexican
      American donor population would expect a higher percent incompatibility. Since
      the Mexican American population is increasing in South Texas and several other
      areas in the United States, the antibody may become increasingly important in
      transfusion therapy and as a cause of hemolytic disease of the newborn.

PMID- 17181124
TI  - Introducing clinical laboratory science: CLS students help shape the future.
AB  - OBJECTIVES: The profession of clinical laboratory science (CLS) is in dire need
      of increased exposure to young people. By introducing the clinical laboratory
      sciences to students at a critical point in their science education and by making
      it relevant to their lives, more choices are made available to them when
      considering future career options. With this in mind, the CLS faculty at Texas
      Tech University Health Sciences Center (TTUHSC) redesigned a recruitment program
      and developed it into one making use of CLS student knowledge, enthusiasm, and
      professionalism. CLS students were given the assignment of designing an entire
      curriculum for a ten day presentation of clinical laboratory science topics to
      middle and secondary school students. Following the presentations, participants
      in the program were asked to provide feedback regarding CLS student performance
      and overall opinion of their interest in clinical laboratory science. The
      objectives of this study were twofold: 1) to determine if educational
      methodologies could be appropriately applied by CLS students to present CLS
      disciplines to middle and high school students; and 2) to determine if the
      student presentation was successful in initiating interest in the CLS profession
      based on outcome measures. DESIGN: As a component of the CLS laboratory
      management course, CLS students were instructed in education methodologies
      including objective writing, teaching-unit preparation, and evaluation tool
      design. In the following semester, these students were divided into groups and
      assigned a specific CLS discipline that would then be presented to middle and
      secondary school students in a two week, 30 hour educational program. This
      program was offered by the TTUHSC CLS program in cooperation with the Institute
      for the Development and Enrichment of Advanced Learners (IDEAL) at Texas Tech
      University. The curriculum prepared by the CLS students (with faculty
      supervision) provided the framework for the present study. SETTING: Didactic
      instruction of the CLS students regarding objective writing, curriculum design,
      and preparation of evaluations was included as a component of a CLS laboratory
      management course. The educational program presented by IDEAL in conjunction with
      the TTUHSC CLS program within the School of Allied Health Sciences occurred in
      the CLS student laboratories located in Lubbock, Texas. PARTICIPANTS: TTUHSC
      senior CLS students in a 2 + 2 baccalaureate level CLS program acted as
      instructors in the educational program which was presented to middle and
      secondary school students from around the region. CLS program faculty served as
      supervisors of this program. MAIN OUTCOME MEASURES: Questionnaires with Likert
      scaled responses were used to evaluate outcomes. These questionnaires regarded 1)
      faculty assessment of CLS student performance relative to instruction in
      education methods; 2) participant feedback on the effectiveness and competence of
      the CLS student instructors and overall appeal of the presented subject material;
      and 3) peer evaluations of attitude, contribution, and effort of the group
      members. RESULTS: CLS faculty strongly agreed that the CLS students demonstrated
      a high level of competence when writing objectives, planning age-appropriate
      curriculum and activities, and demonstrating a positive image of the profession.
      Regarding satisfaction of the IDEAL student participant, questionnaire responses
      demonstrated a high rate (84% or greater for middle school participants and 85%
      for high school students). The program design has been so successful that it has
      been implemented for several other programs offered by TTU and IDEAL. CONCLUSION:
      The education methods used in presenting the IDEAL program mirror those found in
      clinical and academic settings and is an effective technique to introduce CLS
      students to the varied aspects of educational methodology. The presentation by
      the CLS students also demonstrated that introduction of clinical laboratory
      science disciplines early in the education of middle and secondary school
      students leads to an interest in the CLS profession and to the desire to learn
      more about it.

PMID- 17181125
TI  - The use of B-type natriuretic peptide to diagnose congestive heart failure.
AB  - This paper explains the background and current use of B-type natriuretic peptide
      (BNP) assays to differentiate congestive heart failure (CHF) from other causes of
      dyspnea. With a large and growing elderly population, CHF is being diagnosed much
      more often in emergency rooms in the United States. Doctors need a way to quickly
      distinguish whether a patient with respiratory distress is suffering from cardiac
      insufficiency or another etiology. BNP is released from the ventricles in
      response cardiac overload from CHF or some other form of left ventricular
      systolic dysfunction. Therefore, the detection and measurement of BNP is a fast
      and accurate method of determining if CHF is the cause of a patient's breathing
      difficulties.

PMID- 17181126
TI  - Factor V Leiden: an overview.
AB  - This paper provides an update and an overview of factor V Leiden, an inherited
      condition, which predisposes affected individuals to thrombosis. Factor V Leiden
      occurs due to a single point mutation on chromosome one. Tests for factor V
      Leiden include screening for activated protein C (APC) resistance, and if
      positive, testing for the Factor V Leiden mutation.

PMID- 17181127
TI  - Two non-invasive diagnostic tools for invasive aspergilosis: (1-3)-beta-D-glucan
      and the galactomannan assay.
AB  - Invasive aspergillosis (IA) is a serious cause of morbidity and mortality among
      immunocompromised patients. Prompt and non-invasive methods for diagnosing IA are
      needed to improve the management of this life-threatening infection in patients
      with hematological disorders. In summary, this retrospective review of studies
      performed on the two assays finds that both assays have high sensitivity and
      specificity but are more useful when used together as a diagnostic strategy for
      patients with invasive aspergillosis.

PMID- 17181128
TI  - Cessation of menstruation improves the correlation of FPG to hemoglobin A1c in
      Caucasian women.
AB  - BACKGROUND: Anemia is known to cause spurious hemoglobin A1c (HbA1c) results. The
      effect of menstruation on HbA1c was tested by correlating it to FPG in non-anemic
      premenopausal and in menopausal women. METHOD: Non-diabetic, non-obese middle
      aged Caucasian women were classified as premenopausal or menopausal. Hemogram,
      FPG, and A1c results were obtained. RESULTS: Hemoglobin concentrations were lower
      in the premenopausal group. FPG showed a poor correlation to A1c value overall (r
      = 0.251, p = 0.001) which was improved by multiplying the A1c % by the total
      hemoglobin concentration to create an absolute A1c value (r = 0.362, p = 0.000).
      When the data was sorted by menopause status, the correlation of FPG to Absolute
      A1c improved (r = 0.463, p = 0.000) in the menopausal women, but remained low (r
      = 0.283, p = 0.005) in the premenopausal women. CONCLUSIONS: Menstruation may be
      a significant factor affecting the accuracy of A1c concentrations.

PMID- 17181129
TI  - An overview of the human immunodeficiency virus featuring laboratory testing for
      drug resistance.
AB  - The human immunodeficiency virus (HIV) pandemic is unique in human history in its
      rapid spread, its persistence, and the depth of its impact. The Joint United
      Nations Programme on HIV/AIDS (UNAIDS) estimates that approximately 65 million
      people have been infected with HIV since the beginning of the epidemic. During
      this time, approximately 25 million people have died from acquired immune
      deficiency syndrome AIDS. HIV-associated morbidity and mortality was
      substantially reduced during the last decade following the introduction of highly
      active antiretroviral therapy (HAART). In spite of the striking success of HAART
      in treating HIV infection, many patients experience treatment failure as genetic
      changes emerge in the virus leading to drug resistance. Laboratory testing for
      drug resistance in HIV strains is now used in combination with other methods to
      guide antiretroviral therapy. The purpose of this report is to review the
      background information on HIV with the focus on the problem of drug resistance
      and to describe the laboratory methods of testing for drug resistance in HIV
      strains.

PMID- 17181130
TI  - Contactless optical scanning of fingerprints with 180 degrees view.
AB  - Fingerprint recognition technology is an integral part of criminal
      investigations. It is the basis for the design of numerous security systems in
      both the private and public sectors. In a recent study emulating the
      fingerprinting procedure with widely used optical scanners, it was found that, on
      average, the distance between ridges decreases about 20% when a finger is
      positioned on a scanner. Using calibrated silicon pressure sensors, the authors
      scanned the distribution of pressure across a finger, pixel by pixel, and also
      generated maps of the average pressure distribution during fingerprinting.
      Controlled loading of a finger demonstrated that it is impossible to reproduce
      the same distribution of pressure across a given finger during repeated
      fingerprinting procedures. Based on this study, a novel method of scanning the
      fingerprint with more than a 180 degrees view was developed. Using a camera
      rotated around the finger, small slices of the entire image of the finger were
      acquired. Equal sized slices of the image were processed with a special program
      assembling a more than 180 degrees view of the finger. Comparison of two images
      of the same fingerprint, namely the registered and actual images, could be
      performed by a new algorithm based on the symmetry of the correlation function.
      The novel method is the first contactless optical scanning technique to view 180
      degrees of a fingerprint without moving the finger. In a machine which is under
      design, it is expected that the full view of one finger would be acquired in
      about a second.

PMID- 17181131
TI  - Differential interference contrast and confocal reflectance imaging of collagen
      organization in three-dimensional matrices.
AB  - The remodeling of extracellular matrices by cells plays a defining role in
      developmental morphogenesis and wound healing as well as in tissue engineering.
      Three-dimensional (3-D) type I collagen matrices have been used extensively as an
      in vitro model for studying cell-induced matrix reorganization at the macroscopic
      level. However, few studies have directly assessed the process of 3-D
      extracellular matrix (ECM) remodeling at the cellular and subcellular level. In
      this study, we directly compare two imaging modalities for both quantitative and
      qualitative imaging of 3-D collagen organization in vitro: differential
      interference contrast (DIC) and confocal reflectance imaging. The results
      demonstrate that two-dimensional (2-D) DIC images allow visualization of the same
      population of collagen fibrils as observed in 2-D confocal reflectance images.
      Thus, DIC can be used for qualitative assessment of fibril organization, as well
      as tracking of fibril movement in sequential time-lapse 2-D images. However, we
      also found that quantitative techniques that can be applied to confocal
      reflectance images, such as Fourier transform analysis, give different results
      when applied to DIC images. Furthermore, common techniques used for 3-D
      visualization and reconstruction of confocal reflectance datasets are not
      generally applicable to DIC. Overall, obtaining a complete understanding of cell
      matrix mechanical interactions will likely require a combination of both wide
      field DIC imaging to study rapid changes in ECM deformation which can occur
      within minutes, and confocal reflectance imaging to assess more gradual changes
      in cell-induced compaction and alignment of ECM which occur over a longer time
      course.

PMID- 17181132
TI  - Pressure effect of growing with electron beam-induced deposition with tungsten
      hexafluoride and tetraethylorthosilicate precursor.
AB  - Electron beam-induced deposition (EBID) provides a simple way to fabricate
      submicron- or nanometer-scale structures from various elements in a scanning
      electron microscope (SEM). The growth rate and shape of the deposits are
      influenced by many factors. We have studied the growth rate and morphology of
      EBID-deposited nanostructures as a function of the tungsten hexafluoride (WF6)
      and tetraethylorthosilicate (TEOS) precursor gas pressure and growth time, and we
      have used Monte Carlo simulations to model the growth of tungsten and silicon
      oxide to elucidate the mechanisms involved in the EBID growth. The lateral radius
      of the deposit decreases with increasing pressure because of the enhanced
      vertical growth rate which limits competing lateral broadening produced by
      secondary and forward-scattered electrons. The morphology difference between the
      conical SiO(x) and the cylindrical W nanopillars is related to the difference in
      interaction volume between the two materials. A key parameter is the residence
      time of the precursor gas molecules. This is an exponential function of the
      surface temperature; it changes during nanopillar growth and is a function of the
      nanopillar material and the beam conditions.

PMID- 17181133
TI  - Spectral characteristics of autofluorescence and second harmonic generation from
      ex vivo human skin induced by femtosecond laser and visible lasers.
AB  - The spectral properties of one-photon, two-photon excited autofluorescence and
      second harmonic generation (SHG) from ex vivo human skin induced by a femtosecond
      (fs) laser and three visible lasers in backscattering geometry are systematically
      investigated. Our experimental results indicate that peak position of
      autofluorescence spectra from the dermis and epidermis shift toward long
      wavelengths, and the fluorescent intensity decreases when the excitation
      wavelength increases due to an effect of the excitation wavelength on
      autofluorescence signals. However, the intensity of the SHG signal in collagen
      has the maximal value of 800 nm excitation wavelength. This may be the result
      that the energy of the SHG signal is in resonance with an electronic absorption
      band. The two-photon excited autofluorescence and SHG intensity all obey a
      quadratical dependence on the excitation power. Compared with the two-photon
      excited fluorescence and SHG, the one-photon excited fluorescence in the dermis
      and epidermis exhibits different spectral characteristics. The investigation of
      the spectral characteristics of autofluorescence and SHG from ex vivo human skin
      can provide new insights into morphologic structures and biochemical components
      of tissues, which are vital for improving the application of laser-induced
      autofluorescence and SHG spectroscopy technique for noninvasive in vivo tissue
      diagnostics.

PMID- 17181134
TI  - Microstructural characterization of degradation in a high-chromium alloy in the
      sugar industry.
AB  - A new high (24%)-chromium alloy was experimentally manufactured by combining the
      particular chemical composition of various materials with the use of thermal
      treatments to produce pump impellers for the sugar industry. The alloy metal was
      tested in situ in a sugar medium and then evaluated by electrochemical
      measurements; the two former procedures were associated with a nontraditional
      method to assess the susceptibility and resistance to corrosion. Potentiostatic
      and atomic absorption measurements were carried out to characterize the
      degradation and damage morphology by scanning electron microscopy (SEM)
      observations. The trials proved a good performance for the new alloy in the sugar
      medium in spite of nonsignificant localized damages involving erosion-corrosion
      mechanisms and surface microcrackings of the material.

PMID- 17181135
TI  - An accurate approximation for the highly efficient sampling of polar scattering
      angle of electron elastic single-scattering events.
AB  - In single-event Monte Carlo electron transport simulations, elastic scattering
      events dominate the changes in electron trajectories due to collisions.
      Classically, the polar scattering angle due to an elastic collision can be
      sampled efficiently from the screened Rutherford cross section. However, the
      screened Rutherford cross section fails for both high Z materials and when the
      incident electron energy becomes too low. Alternatively, improved simulation
      accuracy for electrons in all energy ranges and through all materials may be
      obtained by sampling directly from differential data derived from partial-wave
      expansion method (PWEM) calculations based on theoretical atomic potential
      models. While sampling directly from wave calculations will yield simulation
      results to the best known physical accuracy, it comes at the cost of simulation
      time. This is due to a sampling process that is typically more involved when
      compared with using the screened Rutherford cross section. In this work we
      present a relationship capable of reproducing the moments of the differential
      cross section derived from PWEM calculations, resulting in good preservation of
      forward and backscattering peaks. The relationship is directly invertible and is
      as easily sampled as the Rutherford cross section. Most important, the data
      presented in this paper in combination with this relationship produce Monte Carlo
      simulation results which are comparable with those using the exact differential
      cross section from PWEM calculations for elements Z = 1 to 96 and for incident
      electron energies from 300,000 down to 50 eV.

PMID- 17181136
TI  - NIH picks up where internet stalls.

PMID- 17181137
TI  - Structure-brain exposure relationships.

PMID- 17181138
TI  - Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2
      methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a novel,
      acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity.
AB  - The discovery of novel acyclic amide cannabinoid-1 receptor inverse agonists is
      described. They are potent, selective, orally bioavailable, and active in rodent
      models of food intake and body weight reduction. A major focus of the
      optimization process was to increase in vivo efficacy and to reduce the potential
      for formation of reactive metabolites. These efforts led to the identification of
      compound 48 for development as a clinical candidate for the treatment of obesity.

PMID- 17181139
TI  - Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer
      gamma-secretase modulators.
AB  - N-sulfonylated and N-alkylated carprofen derivatives were investigated for their
      inhibition and modulation of gamma-secretase, which is associated with
      Alzheimer's disease. The introduction of a lipophilic substituent transformed the
      COX-2 inhibitor carprofen into a potent gamma-secretase modulator. Several
      compounds (e.g., 9p, 11f) caused selective reduction of Abeta42 and an increase
      of Abeta38. The most active compounds displayed activities in the low micromolar
      range and no effect on the gamma-secretase cleavage at the e-site.

PMID- 17181140
TI  - Synthesis of low-hemolytic antimicrobial dehydropeptides based on gramicidin s.
AB  - The synthesis and biological activity of a novel cyclic beta-sheet-type
      antimicrobial dehydropeptide based on gramicidin S (GS) is described. The GS
      analogue, containing two (Z)-(beta-3-pyridyl)-alpha,beta-dehydroalanine
      (DeltaZ3Pal) residues at the 4 and 4' positions (2), was synthesized by solution
      phase methodologies using Boc-Leu-DeltaZ3Pal azlactone. Analogue 2 exhibited high
      antimicrobial activity against Gram-positive bacteria and had much lower
      hemolytic activity than wild-type GS and the corresponding (Z)-alpha,beta
      dehydrophenylalanine (DeltaZPhe) analogue (1).

PMID- 17181141
TI  - Discovery of potent, orally-active, and muscle-selective androgen receptor
      modulators based on an N-aryl-hydroxybicyclohydantoin scaffold.
AB  - A novel, N-aryl-bicyclohydantoin selective androgen receptor modulator scaffold
      was discovered through structure-guided modifications of androgen receptor
      antagonists. A prototype compound (7R,7aS)-10b from this series is a potent and
      highly tissue-selective agonist of the androgen receptor. After oral dosing in a
      rat atrophied levator ani muscle model, (7R,7aS)-10b demonstrated efficacy at
      restoring levator ani muscle mass to that of intact controls and exhibited >50
      fold selectivity for muscle over prostate.

PMID- 17181142
TI  - New benzopyran-based openers of the mitochondrial ATP-sensitive potassium channel
      with potent anti-ischemic properties.
AB  - This study was aimed at evaluating, on a limited number of benzopyran compounds,
      whether the insertion of an electron-rich spirocyclic substituent at the C4
      carbon of the benzopyran molecular nucleus may improve the cardioprotective
      properties against ischemia. Some of the new compounds (1b, 2b, and 4b) exhibited
      interesting anti-ischemic properties without affecting significantly the blood
      pressure parameters.

PMID- 17181143
TI  - Discovery of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5- methylfuran-2
      yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123): a potent,
      orally bioavailable CXCR2/CXCR1 receptor antagonist.
AB  - Structure-activity studies on lead cyclobutenedione 3 led to the discovery of 4
      (SCH 527123), a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist with
      excellent cell-based activity. Compound 4 displayed good oral bioavailability in
      rat and may be a potential therapeutic agent for the treatment of various
      inflammatory diseases.

PMID- 17181144
TI  - Novel multipotent tacrine-dihydropyridine hybrids with improved
      acetylcholinesterase inhibitory and neuroprotective activities as potential drugs
      for the treatment of Alzheimer's disease.
AB  - In this work we describe the synthesis and biological evaluation of the tacrine
      1,4-dihydropyridine (DHP) hybrids (3-11). These multipotent molecules are the
      result of the juxtaposition of an acetylcholinesterase inhibitor (AChEI) such as
      tacrine (1) and a 1,4-DHP such as nimodipine (2). Compounds 3-11 are very
      selective and potent AChEIs and show an excellent neuroprotective profile and a
      moderate Ca2+ channel blockade effect. Consequently, these molecules are new
      potential drugs for the treatment of Alzheimer's disease.

PMID- 17181145
TI  - Design, synthesis, potency, and cytoselectivity of anticancer agents derived by
      parallel synthesis from alpha-aminosuberic acid.
AB  - Chemotherapy in the last century was characterized by cytotoxic drugs that did
      not discriminate between cancerous and normal cell types and were consequently
      accompanied by toxic side effects that were often dose limiting. The ability of
      differentiating agents to selectively kill cancer cells or transform them to a
      nonproliferating or normal phenotype could lead to cell- and tissue-specific
      drugs without the side effects of current cancer chemotherapeutics. This may be
      possible for a new generation of histone deacetylase inhibitors derived from
      amino acids. Structure-activity relationships are now reported for 43 compounds
      derived from 2-aminosuberic acid that kill a range of cancer cells, 26 being
      potent cytotoxins against MM96L melanoma cells (IC50 20 nM-1 microM), while 17
      were between 5- and 60-fold more selective in killing MM96L melanoma cells versus
      normal (neonatal foreskin fibroblasts, NFF) cells. This represents a 10- to 100
      fold increase in potency and up to a 10-fold higher selectivity over previously
      reported compounds derived from cysteine (J. Med. Chem. 2004, 47, 2984).
      Selectivity is also an underestimate, because the normal cells, NFF, are rarely
      all killed by the drugs that also induce selective blockade of the cell cycle for
      normal but not cancer cells. Selected compounds were tested against a panel of
      human cancer cell lines (melanomas, prostate, breast, ovarian, cervical, lung,
      and colon) and found to be both selective and potent cytotoxins (IC50 20 nM-1
      microM). Compounds in this class typically inhibit human histone deacetylases, as
      evidenced by hyperacetylation of histones in both normal and cancer cells, induce
      expression of p21, and differentiate surviving cancer cells to a nonproliferating
      phenotype. These compounds may be valuable leads for the development of new
      chemotherapeutic agents.

PMID- 17181148
TI  - A comparative molecular field analysis (CoMFA) and comparative molecular
      similarity indices analysis (CoMSIA) of anthranilamide derivatives that are
      multidrug resistance modulators.
AB  - In a continuing effort to develop potent and selective modulators of P
      glycoprotein (P-gp) activity overcoming the chemoresistance acquired by tumor
      cells during cancer chemotherapy, we developed 3D quantitative structure-activity
      relationship (3D QSAR) models using CoMFA and CoMSIA analyses. This study
      correlates the P-glycoprotein inhibitory activities of 49 structurally related
      anthranilamide derivatives to several physicochemical parameters representing
      steric, electrostatic, acceptor, donor, and hydrophobic fields. Both CoMFA and
      CoMSIA models using three different alignment conformations gave good internal
      predictions, and their cross-validated r2 values are between 0.503 and 0.644.
      These most comprehensive CoMFA and CoMSIA models are useful in understanding the
      structure-activity relationships of anthranilamide derivatives as well as aid in
      the design of novel derivatives with enhanced modulation of P-gp activity.

PMID- 17181147
TI  - Synthesis of novel caspase inhibitors for characterization of the active caspase
      proteome in vitro and in vivo.
AB  - Caspases are cysteine proteases that are essential for cytokine maturation and
      apoptosis. To facilitate the dissection of caspase function in vitro and in vivo,
      we have synthesized irreversible caspase inhibitors with biotin attached via
      linker arms of various lengths (12a-d) and a 2,4-dinitrophenyl labeled inhibitor
      (13). Affinity labeling of apoptotic extracts followed by blotting reveals that
      these affinity probes detect active caspases. Using the strong affinity of avidin
      for biotin, we have isolated affinity-labeled caspase 6 from apoptotic cytosolic
      extracts of cells overexpressing procaspase 6 by treatment with 12c, which
      contains biotin attached to the N(epsilon)-lysine of the inhibitor by a 22.5 A
      linker arm, followed by affinity purification on monomeric avidin-sepharose
      beads. Compound 13 has proven sufficiently cell permeable to rescue cells from
      apoptotic execution. These novel caspase inhibitors should provide powerful
      probes for the study of the active caspase proteome during apoptosis both in
      vitro and in vivo.

PMID- 17181146
TI  - Antitubercular nucleosides that inhibit siderophore biosynthesis: SAR of the
      glycosyl domain.
AB  - Tuberculosis is the leading cause of infectious disease mortality in the world by
      a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of
      the adenylation enzyme MbtA, which is responsible for the second step of
      mycobactin biosynthesis, exhibited potent antitubercular activity. Here we
      systematically investigate the structure-activity relationships of the
      bisubstrate inhibitor glycosyl domain resulting in the identification of a
      carbocyclic analogue that possesses a KIapp value of 2.3 nM and MIC99 values of
      1.56 microM against M. tuberculosis H37Rv. The SAR data suggest the intriguing
      possibility that the bisubstrate inhibitors utilize a transporter for entry
      across the mycobacterial cell envelope. Additionally, we report improved
      conditions for the expression of MbtA and biochemical analysis, demonstrating
      that MbtA follows a random sequential enzyme mechanism for the adenylation half
      reaction.

PMID- 17181149
TI  - Modeling subtype-selective agonists binding with alpha4beta2 and alpha7 nicotinic
      acetylcholine receptors: effects of local binding and long-range electrostatic
      interactions.
AB  - The subtype-selective binding of 14 representative agonists with alpha4beta2 and
      alpha7 nicotinic acetylcholine receptors (nAChRs) has been studied by performing
      homology modeling, molecular docking, geometry optimizations, and microscopic and
      phenomenological binding free energy calculations. All of the computational
      results demonstrate that the subtype selectivity of the agonists binding with
      alpha4beta2 and alpha7 7 nAChRs is affected by both local binding and long-range
      electrostatic interactions between the receptors and the protonated structures of
      the agonists. The effects of the long-range electrostatic interactions are mainly
      due to the distinct difference in the net charge of the ligand-binding domain
      between the two nAChR subtypes. For the alpha4beta2-selective agonists examined,
      the microscopic binding modes with the alpha4beta2 nAChR are very similar to the
      corresponding modes with the alpha7 nAChR, and therefore, the subtype selectivity
      of these agonists binding with alpha4beta2 and alpha7 nAChRs is dominated by the
      long-range electrostatic interactions. For the alpha7-selective agonists, their
      microscopic binding modes with the alpha7 nAChR are remarkably different from
      those with the alpha4beta2 nAChR so that the local binding (including the
      hydrogen bonding and cation-pi interactions) with the alpha7 nAChR is much
      stronger than that with the alpha4beta2 nAChR. The calculated phenomenological
      binding free energies are in good agreement with available experimental data for
      the relative binding free energies concerning the subtype selectivity of agonists
      binding with the two different nAChR subtypes. The fundamental insights obtained
      in the present study should be valuable for future rational design of potential
      therapeutic agents targeted to specific nAChR subtypes.

PMID- 17181150
TI  - Insights on resistance to reverse transcriptase: the different patterns of
      interaction of the nucleoside reverse transcriptase inhibitors in the
      deoxyribonucleotide triphosphate binding site relative to the normal substrate.
AB  - It is presently known that the long-term failure in the treatment of AIDS with
      the currently available nucleotide reverse transcriptase inhibitors (NRTIs) is
      related to the development of resistance by reverse transcriptase (RT) at the
      binding or incorporation level or both, or subsequent to the nucleotide
      incorporation (excision). To achieve greater insight on the differential
      interactions of two NRTIs that are mainly discriminated by different mechanisms,
      2',3'-didehydro-2',3'-dideoxythymidine-5'-triphosphate (d4TTP, that is,
      phosphorylated stavudine) and 2',3'-dideoxycytidine-5'-triphosphate (ddCTP, that
      is, phosphorylated zalcitabine), with the primer/template (p/t) and with the N
      binding site of reverse transcriptase (RT) in relation to the normal substrate
      (dNTP), we have conducted a series of molecular dynamics (MD) simulations. We
      propose that the different resistance profiles arise from the different
      conformations adopted by the inhibitors at the N site. d4TTP adopts an ideal
      conformation for catalysis because it forms an ion-dipole intramolecular
      interaction with the beta-phosphate oxygen of the triphosphate, as does the
      normal substrate. In ddCTP, the lack of this essential interaction results in a
      different, noncatalytic conformation.

PMID- 17181151
TI  - 2-substituted estradiol bis-sulfamates, multitargeted antitumor agents:
      synthesis, in vitro SAR, protein crystallography, and in vivo activity.
AB  - The anticancer activities and SARs of estradiol-17-O-sulfamates and estradiol
      3,17-O,O-bis-sulfamates (E2bisMATEs) as steroid sulfatase (STS) inhibitors and
      antiproliferative agents are discussed. Estradiol 3,17-O,O-bis-sulfamates 20 and
      21, in contrast to the 17-O-monosulfamate 11, proved to be excellent STS
      inhibitors. 2-Substituted E2bisMATEs 21 and 23 additionally exhibited potent
      antiproliferative activity with mean graph midpoint values of 18-87 nM in the NCI
      60-cell-line panel. 21 Exhibited antiangiogenic in vitro and in vivo activity in
      an early-stage Lewis lung model, and 23 dosed p.o. caused marked growth
      inhibition in a nude mouse xenograft tumor model. Modeling studies suggest that
      the E2bisMATEs and 2-MeOE2 share a common mode of binding to tubulin, though
      COMPARE analysis of activity profiles was negative. 21 was cocrystallized with
      carbonic anhydrase II, and X-ray crystallography revealed unexpected coordination
      of the 17-O-sulfamate of 21 to the active site zinc and a probable additional
      lower affinity binding site. 2-Substituted E2bisMATEs are attractive candidates
      for further development as multitargeted anticancer agents.

PMID- 17181152
TI  - Rapid discovery and structure-activity profiling of novel inhibitors of human
      immunodeficiency virus type 1 protease enabled by the copper(I)-catalyzed
      synthesis of 1,2,3-triazoles and their further functionalization.
AB  - Building from the results of a computational screen of a range of triazole
      containing compounds for binding efficiency to human immunodeficiency virus type
      1 protease (HIV-1-Pr), a novel series of potent inhibitors has been developed.
      The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), which provides ready
      access to 1,4-disubstituted-1,2,3-triazoles, was used to unite a focused library
      of azide-containing fragments with a diverse array of functionalized alkyne
      containing building blocks. In combination with direct screening of the crude
      reaction products, this method led to the rapid identification of a lead
      structure and readily enabled optimization of both azide and alkyne fragments.
      Replacement of the triazole with a range of alternative linkers led to greatly
      reduced protease inhibition; however, further functionalization of the triazoles
      at the 5-position gave a series of compounds with increased activity, exhibiting
      Ki values as low as 8 nM.

PMID- 17181153
TI  - Synthesis and characterization of a novel liver-targeted prodrug of cytosine-1
      beta-D-arabinofuranoside monophosphate for the treatment of hepatocellular
      carcinoma.
AB  - Cytotoxic nucleosides have proven to be ineffective for the treatment of
      hepatocellular carcinoma (HCC) due, in part, to their inadequate conversion to
      their active nucleoside triphosphates (NTP) in the liver tumor and high
      conversion in other tissues. These characteristics lead to poor efficacy, high
      toxicity, and a drug class associated with an unacceptable therapeutic index.
      Cyclic 1-aryl-1,3-propanyl phosphate prodrugs selectively release the
      monophosphate of a nucleoside (NMP) into CYP3A4-expressing cells, such as
      hepatocytes, while leaving the prodrug intact in plasma and extrahepatic tissues.
      This prodrug strategy was applied to the monophosphate of the well-known
      cytotoxic nucleoside cytosine-1-beta-D-arabinofuranoside (cytarabine, araC).
      Compound 19S (MB07133), in mice, achieves good liver targeting compared to araC,
      generating >19-fold higher cytarabine triphosphate (araCTP) levels in the liver
      than levels of araC in the plasma and >12-fold higher araCTP levels in the liver
      than in the bone marrow, representing a >120-fold and >28-fold improvement,
      respectively, over araC administration.

PMID- 17181154
TI  - Small-molecule targeting of heat shock protein 90 chaperone function: rational
      identification of a new anticancer lead.
AB  - Heat shock protein 90 (Hsp90) is a significant target in the development of
      rational cancer therapy due to its role at the crossroads of multiple signaling
      pathways associated with cell proliferation and cell viability. Here we present a
      combined structure- and dynamics-based computational design strategy, taking the
      flexibility of the receptor and of a lead peptidic antagonist into account
      explicitly, to identify the nonpeptidic small molecule 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside (AICAR) as a structurally novel inhibitor of
      Hsp90. The compound is selected to bind the Hsp90 N-terminal domain, mimicking
      the chemical and conformational properties of the recently described peptidic
      antagonist of the survivin-Hsp90 complex, shepherdin [Plescia et al. Cancer Cell
      2005, 7, 457-468]. Experimental tests show that AICAR binds the Hsp90 N-domain,
      destabilizes multiple Hsp90 client proteins in vivo, including survivin, and
      exhibits antiproliferative and proapoptotic activity in multiple tumor cell
      lines, while not affecting proliferation of normal human fibroblasts. We propose
      that AICAR represents a viable lead for further development of anticancer drugs
      with wide therapeutic opportunities.

PMID- 17181155
TI  - Structure-activity relationship studies of ethyl 2-amino-6-bromo-4-(1-cyano-2
      ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA 14-1), an antagonist for
      antiapoptotic Bcl-2 proteins to overcome drug resistance in cancer.
AB  - The structure-activity relationship studies of ethyl 2-amino-6-cyclopentyl-4-(1
      cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (1, HA 14-1), an antagonist
      of the antiapoptotic Bcl-2 proteins, are reported. A series of analogues of 1
      with varied functional groups at the 6-position of the chromene ring were
      synthesized. These candidates were evaluated for their binding interactions with
      three antiapoptotic proteins: Bcl-2, Bcl-XL, and Bcl-w. They were also assayed
      for their in vitro cytotoxicities against a set of Jurkat cells with varied
      levels of Bcl-2 and Bcl-XL proteins and a non-small-cell lung carcinoma cell line
      (NCI-H460). It was found that the 6-bromo of 1 was not essential for its
      bioactivity and the 6-position can accommodate a variety of alkyl groups. 1 and
      its analogues bind to all of the three antiapoptotic Bcl-2 proteins tested.
      Positive correlations were observed between the binding affinities of these
      candidates to the antiapoptotic Bcl-2 proteins and their in vitro cytotoxicities,
      suggesting that the antiapoptotic Bcl-2 proteins are likely to be the cellular
      targets of 1 and its analogues. (In this study, the binding interactions of the
      small molecules to antiapoptotic Bcl-2 proteins were studied by assaying their
      abilities to compete against a Bak peptide binding to the antiapoptotic Bcl-2
      proteins. Inhibitory constants, instead of dissociation constants, were obtained
      in such assays. The term "binding affinity" is used in this article for
      simplicity.) The most active compound, 3g, had a >3-fold increase of binding
      affinity to the antiapoptotic Bcl-2 proteins and a >13-fold increase of in vitro
      cytotoxicity over 1. Though Jurkat cells with transgenic overexpression of Bcl-2
      or Bcl-XL protein can develop resistance to standard cancer therapies, such cells
      failed to develop resistance to 1 based candidates. 1 also sensitizes Jurkat
      cells to cisplatin. These studies provide further support that 1 and its
      analogues function as antagonists for antiapoptotic Bcl-2 proteins and that they
      have the potential, either as a single agent or as a combination therapy with
      other anticancer agents, to treat cancers with the overexpression of
      antiapoptotic Bcl-2 proteins.

PMID- 17181156
TI  - A systematic study of nitrated indenoisoquinolines reveals a potent topoisomerase
      I inhibitor.
AB  - The biological activity of indenoisoquinoline topoisomerase I inhibitors is
      significantly enhanced by nitration of the isoquinoline ring. In the present
      study, nitrated analogues were synthesized with the indenone ring substituted
      with methoxy groups to further explore a previously identified structure-activity
      relationship between the nitrated isoquinoline ring and a methylenedioxy
      substituted indenone ring. The results indicate that a single methoxy group at
      the 9-position of an indenoisoquinoline affords superior biological activity.
      Hypothetical binding models have been developed to rationalize these results, and
      they indicate that pi-stacking between the indenoisoquinolines and the DNA base
      pairs, as visualized by electrostatic complementarity, is important for the
      intercalation and biological activity of the indenoisoquinoline analogues.
      Collectively, the analysis of methoxy groups on the indenone ring also
      illustrates a strict steric requirement for substituents extending toward the
      nonscissile DNA backbone and emphasizes a need for planarity to afford potent
      biological activity.

PMID- 17181158
TI  - N1-substituted thymine derivatives as mitochondrial thymidine kinase (TK-2)
      inhibitors.
AB  - Novel N1-substituted thymine derivatives related to 1-[(Z)-4-(triphenylmethoxy)-2
      butenyl]thymine have been synthesized and evaluated against thymidine kinase-2
      (TK-2) and related nucleoside kinases [i.e., Drosophila melanogaster
      deoxynucleoside kinase (Dm-dNK) and herpes simplex virus type 1 thymidine kinase
      (HSV-1 TK)]. The thymine base has been tethered to a distal triphenylmethoxy
      moiety through a polymethylene chain (n = 3-8) or through a (2-ethoxy)ethyl
      spacer. Moreover, substitutions at position 4 of one of the phenyl rings of the
      triphenylmethoxy moiety have been performed. Compounds with a hexamethylene
      spacer (18, 26b, 31) displayed the highest inhibitory values against TK-2 (IC50 =
      0.3-0.5 microM). Compound 26b competitively inhibited TK-2 with respect to
      thymidine and uncompetitively with respect to ATP. A rationale for the biological
      data was provided by docking some representative inhibitors into a homology-based
      model of human TK-2. Moreover, two of the most potent TK-2 inhibitors (18 and
      26b) that also inhibit HSV-1 TK were able to reverse the cytostatic activity of 1
      (beta-D-arabinofuranosyl)thymine (Ara-T) and ganciclovir in HSV-1 TK-expressing
      OST-TK-/HSV-1 TK+ cell cultures.

PMID- 17181157
TI  - Topomimetics of amphipathic beta-sheet and helix-forming bactericidal peptides
      neutralize lipopolysaccharide endotoxins.
AB  - Release of lipopolysaccharide (LPS) endotoxin from Gram negative bacterial
      membranes triggers macrophages to produce large quantities of cytokines that can
      lead to septic shock and eventual death. Agents that bind to and neutralize LPS
      may provide a means to clinically prevent septic shock upon bacterial infection.
      Previously, we reported the design of antibacterial helix peptide SC4 and beta
      sheet-forming betapep peptides that neutralize LPS in vitro. We hypothesized that
      the ability of these and other such peptides to neutralize LPS rested in the
      common denominator of positively charged amphipathic structure. Here, we describe
      the design and synthesis of nonpeptide, calixarene-based helix/sheet topomimetics
      that mimic the folded conformations of these peptides in their molecular
      dimensions, amphipathic surface topology, and compositional properties. From a
      small library of topomimetics, we identified several compounds that neutralize
      LPS in the 10-8 M range, making them as effective as bactericidal/permeability
      increasing protein and polymyxin B. In an endotoxemia mouse model, three of the
      most in vitro effective topomimetics are shown to be at least partially
      protective against challenges of LPS from different bacterial species. NMR
      studies provide mechanistic insight by suggesting the site of molecular
      interaction between topomimetics and the lipid A component of LPS, with binding
      being mediated by electrostatic and hydrophobic interactions. This research
      contributes to the development of pharmaceutical agents against endotoxemia and
      septic shock.

PMID- 17181159
TI  - Synthesis of 2-methyl-3-indolylacetic derivatives as anti-inflammatory agents
      that inhibit preferentially cyclooxygenase 1 without gastric damage.
AB  - Novel substituted 2-methyl-3-indolylacetic derivatives were synthesized and
      evaluated for their activity in vitro and in vivo on COX-1 and COX-2. Active
      compounds were screened to determine their gastrointestinal tolerability in vivo
      in the rat. Results showed that 3 and 4 preferentially inhibited COX-1 in vitro
      and in vivo. MD simulations indicated an induced fit for COX-1 but not for COX-2,
      probably because of a lower plasticity of the latter.

PMID- 17181160
TI  - Design, synthesis, and biological evaluation of peptidomimetic inhibitors of
      factor XIa as novel anticoagulants.
AB  - Human coagulation factor XIa (FXIa), a serine protease activated by site-specific
      cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme
      in the amplification phase of the coagulation cascade. To investigate the
      potential of FXIa inhibitors as safe anticoagulants, a series of potent,
      selective peptidomimetic inhibitors of FXIa were designed and synthesized. Some
      of these inhibitors showed low nanomolar FXIa inhibitory activity with >1000-fold
      FXa selectivity and >100-fold thrombin selectivity. The X-ray structure of one of
      these inhibitors, 36, demonstrates its unique binding interactions with FXIa.
      Compound 32 caused a doubling of the activated partial thromboplastin time in
      human plasma at 2.4 microM and was efficacious in a rat model of venous
      thrombosis. These data suggest that factor XIa plays a significant role in venous
      thrombosis and may be a suitable target for the development of antithrombotic
      therapy.

PMID- 17181161
TI  - Transplatin is cytotoxic when photoactivated: enhanced formation of DNA cross
      links.
AB  - It is well-known that although cisplatin, [cis-[PtCl2(NH3)2], is an anticancer
      drug, its isomer transplatin is not cytotoxic. Here we show that transplatin is
      almost as cytotoxic as cisplatin when treated cells (human keratinocytes HaCaT
      and ovarian cancer A2780 cells) are irradiated with UVA light (50 min, 1.77 mW cm
      2). Chemical studies show that light activates both chloride ligands of
      transplatin, and experiments on pSP73 plasmid DNA and a 23 base-pair DNA duplex
      show that irradiation can greatly enhance formation of interstrand cross-links
      and of DNA-protein cross-links (which are not formed in the dark). Comet assays
      showed that UVA irradiation of transplatin-treated cells resulted in an increased
      inhibition of H2O2-induced DNA migration, supporting the conclusion that the
      cytotoxicity of photoactivated transplatin is mainly due to formation of DNA
      interstrand and DNA-protein cross-links.

PMID- 17181162
TI  - Synthesis, in vitro antiviral evaluation, and stability studies of novel alpha
      borano-nucleotide analogues of 9-[2-(phosphonomethoxy)ethyl]adenine and (R)-9-[2
      (phosphonomethoxy)propyl]adenine.
AB  - We describe here the synthesis of 9-[2-(boranophosphonomethoxy)ethyl]adenine (6a)
      and (R)-9-[2-(boranophosphonomethoxy)propyl]adenine (6b), the first alpha
      boranophosphonate nucleosides in which a borane (BH3) group substitutes one
      nonbridging oxygen atom of the alpha-phosphonate moiety. H-phosphinates 5a and 5b
      and alpha-boranophosphonates 6a and 6b were evaluated for their in vitro activity
      against human immunodeficiency virus (HIV) infected cells and against a panel of
      DNA or RNA viruses. Compounds 5a, 5b, 6a, and 6b exhibited no significant
      antiviral activity in vitro and cytotoxicity. To measure the chemical and
      enzymatic stabilities of the target compounds 6a and 6b, kinetic data of
      decomposition for derivatives 5a, 5b, 6a, 6b, and standard compounds were studied
      at 37 degrees C in several media. The alpha-boranophosphonates 6a and 6b were
      metabolized in culture medium into H-phosphinates 5a and 5b, with half-live
      values of 5.3 h for 6a and 1.3 h for 6b.

PMID- 17181163
TI  - Synthesis and evaluation of multisubstrate bicyclic pyrimidine nucleoside
      inhibitors of human thymidine phosphorylase.
AB  - A series of novel, multisubstrate, bicyclic pyrimidine nucleoside inhibitors of
      human thymidine phosphorylase (TP) is described. Thymidine phosphorylase has been
      implicated in angiogenesis and plays a significant role in tumor progression and
      metastasis. The presence and orientation of the phosphonate moiety (acting as a
      phosphate mimic) in these derivatives were critical for inhibitory activity. The
      most active compounds possessed a phosphonate group in an endo orientation. This
      was consistent with molecular modeling results that showed the endo isomer
      protein-ligand complex to be lower in energy than the exo complex.

PMID- 17181164
TI  - 9-Benzylidene-naphtho[2,3-b]thiophen-4-ones as novel antimicrotubule agents
      synthesis, antiproliferative activity, and inhibition of tubulin polymerization.
AB  - A novel series of 9-benzylidene-naphtho[2,3-b]thiophen-4-ones and structurally
      related compounds were synthesized and evaluated for their ability to inhibit
      tubulin polymerization. The 4-hydroxy-3,5-dimethoxy-benzylidene analogue 15d was
      identified as a potent cytotoxic agent in an assay based on K562 leukemia cells.
      Antiproliferative activity of 15d and the 2,4-dimethoxy-3-hydroxy-benzylidene
      analogue 15e was additionally evaluated against a panel of 12 tumor cell lines,
      including multidrug resistant phenotypes. All resistant cell lines were sensitive
      to these compounds. Concentration-dependent flow cytometric studies showed that
      K562 cells as well as KB/HeLa cells treated by 15d were arrested in the G2/M
      phases of the cell cycle. Moreover, four compounds strongly inhibited tubulin
      polymerization with activities higher or comparable to those of the reference
      compounds. In competition experiments, the most active compounds strongly
      displaced radiolabeled colchicine from its binding site in the tubulin, showing
      IC50 values virtually 3- to 4-fold lower than that of colchicine.

PMID- 17181165
TI  - Arylpiperazinylalkylpyridazinones and analogues as potent and orally active
      antinociceptive agents: synthesis and studies on mechanism of action.
AB  - A number of arylpiperazinylalkylpyridazinones structurally related to the
      previously described lead A (5-{[4-(3-chlorophenyl)piperazin-1-yl]-propyl}-3
      methyl-7-phenylisossazolo[4,5-d]pyridazin-4-(5H)-one) were synthesized and tested
      for their analgesic activity. Many of the tested molecules, at the dose of 20 mg
      kg-1 p.o., showed high antinociceptive activity, in particular, compounds 5a,
      11c, 15a, 21 and 22, which were able to reduce the number of abdominal
      constrictions by more than 50% in writhing test. The pharmacological
      investigation of lead A led us to clarify the mechanism of action of this
      compound, showing that it carries out its analgesic action through the inhibition
      of reuptake of noradrenaline. The antinociception of some of the most interesting
      new molecules was completely prevented by pretreatment with alpha2-antagonist
      yohimbine, suggesting the involvement of alpha2-adrenoceptors, as with prototype
      A.

PMID- 17181167
TI  - Synthesis and structure-activity relationships of 3,8-diazabicyclo[4.2.0]octane
      ligands, potent nicotinic acetylcholine receptor agonists.
AB  - A series of potent neuronal nicotinic acetylcholine receptor (nAChR) ligands
      based on a 3,8-diazabicyclo[4.2.0]octane core have been synthesized and evaluated
      for affinity and agonist efficacy at the human high affinity nicotine recognition
      site (halpha4beta2) and in a rat model of persistent nociceptive pain (formalin
      model). Numerous analogs in this series exhibit picomolar affinity in radioligand
      binding assays and nanomolar agonist potency in functional assays, placing them
      among the most potent nAChR ligands known for the halpha4beta2 receptor. Several
      of the compounds reported in this study (i.e., 24, 25, 28, 30, 32, and 47)
      exhibit equivalent or greater affinity for the halpha4beta2 receptor relative to
      epibatidine, and like epibatidine, many exhibit robust analgesic efficacy in the
      rat formalin model of persistent pain.

PMID- 17181166
TI  - Biological mechanisms of action of novel C-10 non-acetal trioxane dimers in
      prostate cancer cell lines.
AB  - The mechanisms of action of three C-10 non-acetal trioxane dimers (TDs) were
      examined in human (LNCaP) and mouse (TRAMP-C1A and -C2H) prostate cancer cell
      lines. 1 (AJM3/23), 2 (GHP-TM-III-07w), and 3 (GHP-KB-06) inhibited cell growth
      with 3 being the most potent in C1A (GI50 = 18.0 nM), C2H (GI50 = 17.0 nM), and
      LNCaP (GI50 = 17.9 nM) cells. In comparison to a standard cytotoxic agent such as
      doxorubicin (GI50 = 45.3 nM), 3 (GI50 = 17.9 nM) inhibited LNCaP cell growth more
      potently. TDs induced G0/G1 cell cycle arrest in LNCaP cells and decreased cells
      in the S phase. These changes correlated with modulation of G1 phase cell cycle
      proteins including decreased cyclin D1, cyclin E, and cdk2 and increased p21waf1
      and p27Kip1. TDs also promoted apoptosis in LNCaP cells with increased expression
      of proapoptotic bax. These results demonstrate that TDs are potentially useful
      agents that warrant further preclinical development for treatment of prostate
      cancer.

PMID- 17181168
TI  - Synthesis and antituberculosis activity of a novel series of optically active 6
      nitro-2,3-dihydroimidazo[2,1-b]oxazoles.
AB  - In an effort to develop potent new antituberculosis agents that would be
      effective against both drug-susceptible and drug-resistant strains of
      Mycobacterium tuberculosis, we prepared a novel series of optically active 6
      nitro-2,3-dihydroimidazo[2,1-b]oxazoles substituted at the 2-position with
      various phenoxymethyl groups and a methyl group and investigated the in vitro and
      in vivo activity of these compounds. Several of these derivatives showed potent
      in vitro and in vivo activity, and compound 19 (OPC-67683) in particular
      displayed excellent in vitro activity against both drug-susceptible and drug
      resistant strains of M. tuberculosis H37Rv (MIC = 0.006 microg/mL) and dose
      dependent and significant in vivo efficacy at lower oral doses than rifampicin in
      mouse models infected with M. tuberculosis Kurono. The synthesis and structure
      activity relationships of these new compounds are presented.

PMID- 17181169
TI  - Synthesis and anti-human immunodeficiency virus activity of 4'-branched (+/-)-4'
      thiostavudines.
AB  - Motivated by our recent finding that 4'-ethynylstavudine (4) is a promising anti
      human immunodeficiency virus type 1 (HIV-1) agent, we synthesized its 4'-thio
      analogue, as well as other 4'-thiostavudines having a carbon substituent at the
      4'-position, as racemates in this study. Methyl 3-oxo-tetrahydrothiophen-2
      carboxylate (5) was used as a starting material to construct the requisite 4
      thiofuranoid glycal (13). Introduction of a thymine base was carried out by an
      electrophilic addition reaction to 13 using N-iodosuccinimide (NIS) and
      bis(trimethylsilyl)thymine. The desired beta-anomer (16beta) obtained as a major
      product in this reaction underwent ready elimination with activated Zn to give
      the 4'-carbomethoxy derivative (18). By using 18 as a common intermediate, 4'
      carbon-substituted (CH2OH, CO2Me, CONH2, CH=CH2, CN, and C(triple bond)CH) 4'
      thiostavudines were prepared. Among these six compounds, 4'-cyano (28) and 4'
      ethynyl (29) analogues were found to show inhibitory activity against HIV-1 with
      ED50 values of 7.6 and 0.74 microM, respectively. The activity of 29 was
      comparable to that of stavudine, but 29 was not as active as 4. Optical
      resolution of 29 was briefly examined.

PMID- 17181170
TI  - Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5
      methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles.
AB  - Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5
      methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase
      activity. We previously reported that analogs of 1 with thiophene groups at C-7
      retained the Src activity of the parent compound. The corresponding C-7 furan
      analogs were prepared and it was found that the 3,5-substituted furan analog had
      increased activity compared to that of the 2,5-substituted furan isomer. Addition
      of a methoxy group at C-6 decreased the Src inhibitory activity of the C-7 2,5
      substituted furan analog but increased the activity of the C-7 3,5-substituted
      furan isomer. This compound, 10, was a more potent Src inhibitor than 1 in both
      enzymatic and cell-based assays. The kinase selectivity profile of 10 was similar
      to that of 1, with 10 also inhibiting the activity of Abl and Lck. When tested in
      a solid tumor xenograft model, 10 had comparable oral activity to that of 1.

PMID- 17181172
TI  - Quinol-4-ones as steroid A-ring mimetics in nonsteroidal dissociated
      glucocorticoid agonists.
AB  - We report on the nuclear receptor binding affinities, cellular activities of
      transrepression and transactivation, and anti-inflammatory properties of a quinol
      4-one and other A-ring mimetic containing nonsteroidal class of glucocorticoid
      agonists.

PMID- 17181171
TI  - Synthesis, antifungal activity, and structure-activity relationships of
      coruscanone A analogues.
AB  - Coruscanone A, a plant-derived cyclopentenedione derivative, showed potent in
      vitro antifungal activity against Candida albicans and Cryptococcus neoformans
      comparable to amphotericin B and fluconazole. A series of analogues have been
      synthesized by modification of the cyclopentenedione ring, the enolic methoxy
      functionality, and the side chain styryl moiety of this natural product lead. A
      structurally close 1,4-benzoquinone analogue was also prepared. All the compounds
      were examined for their in vitro activity against major opportunistic fungal
      pathogens including C. albicans, C. neoformans, and Aspergillus fumigatus and
      fluconazole-resistant C. albicans strains, with several analogues demonstrating
      potent antifungal activity. Structure-activity relationship studies indicate that
      the 2-methoxymethylenecyclopent-4-ene-1,3-dione structural moiety is the
      pharmacophore responsible for the antifungal activity of this class of compounds
      while the side chain styryl-like moiety plays an important complementary role,
      presumably contributing to target binding.

PMID- 17181173
TI  - Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5
      nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1).
AB  - The design and synthesis of antitumor imidazothiazole guanylhydrazones are
      reported. The compounds were submitted to NCI for testing. All but one were more
      active than methyl-GAG. A few compounds were selected for further studies in
      search of a possible mechanism of action. The results from these studies and a
      final search with the NCI COMPARE algorithm suggest that the guanylhydrazones
      described in this paper are acting through a novel mechanism of action.

PMID- 17181174
TI  - Binding properties of aromatic carbon-bound fluorine.
AB  - A systematic computational analysis of the ability of aromatic carbon-bound
      fluorine to participate in hydrogen bonding and electrostatic interactions has
      been completed. The interaction energies between the most common fluoroaromatics
      used in medicinal chemistry and both water, the prototypical hydrogen bond donor,
      and several cations have been calculated at different levels of theory (HF, MP2,
      DFT). Our results show that aromatic fluorine can participate in significant
      hydrogen bonds and can also interact with charged molecules.

PMID- 17181175
TI  - N,N'-Bisbenzylidenebenzene-1,4-diamines and N,N'-Bisbenzylidenenaphthalene-1,4
      diamines as Sirtuin Type 2 (SIRT2) Inhibitors.
AB  - A series of N,N'-bisbenzylidenebenzene-1,4-diamine and N,N'
      bisbenzylidenenaphthalene-1,4-diamine derivatives were synthesized as inhibitors
      for human sirtuin type 2 (SIRT2). The design of the new compounds was based on
      two earlier reported hits from molecular modeling and virtual screening. The most
      potent compound was N,N'-bis(2-hydroxybenzylidene)benzene-1,4-diamine, which was
      equipotent with the most potent hit compound and well-known SIRT2 inhibitor
      sirtinol.

PMID- 17181176
TI  - Design, synthesis, and biological evaluation of phenylamino-substituted 6,11
      dihydro-dibenzo[b,e]oxepin-11-ones and dibenzo[a,d]cycloheptan-5-ones: novel p38
      MAP kinase inhibitors.
AB  - The pathogenesis of chronic inflammatory diseases is promoted by various pro
      inflammatory cytokines. p38 MAP kinase seems to be a valid target as it controls
      proinflammatory cytokine levels on both transcriptional and translational levels.
      Starting from benzophenone-type inhibitors, a rigidisation strategy lead to 3
      amino-6,11-dihydro-dibenzo[b,e]thiepin-11-one, phenylamino-substituted 6,11
      dihydro-dibenzo[b,e]oxepin-11-ones, and dibenzo[a,d]cyclohepten-5-ones.
      Synthesis, p38 inhibition, and CYP-inhibition of selected compounds are
      described.

PMID- 17181177
TI  - Design, synthesis, and evaluation of a potent, cell-permeable, conformationally
      constrained second mitochondria derived activator of caspase (Smac) mimetic.
AB  - A potent, cell-permeable, conformationally constrained second mitochondria
      derived activator of caspase mimetic (SM-131, 2) has been designed, synthesized,
      and evaluated. Compound 2 binds to X-linked inhibitors of apoptosis proteins
      (XIAP) with a Ki of 61 nM in a competitive binding assay and directly antagonizes
      the XIAP inhibition of caspase-9 activity in a cell-free functional assay.
      Compound 2 achieves an IC50 of 100 nM in inhibition of cell growth and
      effectively induces cell death in the MDA-MB-231 human breast cancer cell line.

PMID- 17181183
TI  - Spin-labeled alkylphospholipids in a dipalmitoylphosphatidylcholine bilayer:
      molecular dynamics simulations.
AB  - Molecular dynamics simulation has been performed to investigate the structural
      properties of perifosine and its synthetic spin-labeled alkylphospholipid
      analogues. The conformations adopted by these compounds in water and in a
      dipalmitoylphosphatidylcholine bilayer as a function of the presence and position
      of the N-oxyl-4',4'-dimethyloxazolidine ring (doxyl group) have been investigated
      by all-atom molecular dynamics. No predominant conformation was observed in
      water, but the molecules adopt specific orientations and conformations in the
      lipid bilayer. As is expected, alkyl chains tend to insert into the hydrophobic
      core, while charged groups stay at the lipid-water interface. A doxyl group in
      the middle of the alkyl chain moves up to the interface region, thus preventing
      adoption of the extended conformation. Compounds with a doxyl group close to the
      polar head group adopt conformations similar to that of unlabeled perifosine
      within the first nanoseconds of simulation. When the doxyl group is at the end of
      alkyl chain, the spin-labeled molecule needs more time to reach equilibrium.
      These results indicate a considerable effect of the doxyl position within the
      alkyl chain on its localization in the lipid bilayer and can be extended further
      to other similar spin probes used in the electron paramagnetic resonance
      spectroscopy of biological membranes.

PMID- 17181184
TI  - Tilt: major factor in sterols' ordering capability in membranes.
AB  - Using extensive atomistic simulations, we show that there is a single
      experimentally accessible parameter--the sterol tilt--that can be used to
      determine a sterol's capability to induce order, and thus to promote, e.g.,
      formation of lipid rafts. The observations also facilitate designing new
      effective sterols.

PMID- 17181185
TI  - Coordination symmetry-dependent structure restoration function of one-dimensional
      MOFs by molecular respiration.
AB  - One-dimensional metal-organic compounds with cis, trans symmetry-controlled
      counter anions were synthesized (cis compound
      {[Cu(azpy)(H2O)2(OTs)2]*2H2O*(acetone)} (1) and trans compound
      {[Cu(H2O)4Cu(azpy)2(OTs)2(H2O)2]*2(OTs)*2H2O*2EtOH} (2)). Only 2, having trans
      conformation, exhibited a complete structure-restoration effect with a mechanism
      involving layering of molecular "bricks" of water and solvent molecules.

PMID- 17181186
TI  - Size-dependent spectroscopic properties of conjugated polymer nanoparticles.
AB  - This paper is focused on how the spectroscopic properties of conjugated polymers
      evolve in the size range between single polymer chains and the bulk material. The
      measurements used single-particle spectroscopy techniques and include both static
      and dynamic measurements. The main observation of this work is that the
      spectroscopic properties of MEH-PPV evolve rapidly as a function of nanoparticle
      size and achieve bulk-like properties for nanoparticles greater than 10 nm in
      size. Nanoparticles were assembled by a reprecipitation technique and
      characterized by fluorescence emission spectroscopy. The physical origin of the
      size-dependent spectroscopic properties is assigned to the distance dependence of
      four main processes: electronic energy transfer between blue and red sites,
      triplet-triplet annihilation, singlet exciton quenching by triplets, and singlet
      exciton quenching by hole polarons.

PMID- 17181187
TI  - Self-assembly of heterogeneous supramolecular structures with uniaxial
      anisotropy.
AB  - Uniaxial anisotropy in two-dimensional self-assembled supramolecular structures
      is achieved by the coadsorption of two different linear molecules with
      complementary amine and imide functionalization. The two-dimensional monolayer is
      defined by a one-dimensional stack of binary chains, which can be forced to line
      up along steps in vicinal surfaces. The competing driving forces in the self
      organization process are discussed in light of the structures observed during
      single molecule adsorption and coadsorption on flat and vicinal surfaces and the
      corresponding theoretical calculations.

PMID- 17181188
TI  - N+NO reaction on Rh(111) surfaces studied with fast near-edge X-ray absorption
      fine structure spectroscopy: role of NO dimer as an extrinsic precursor.
AB  - We studied the mechanism of the N+NO reaction on Rh(111) surfaces by means of
      fast near-edge X-ray absorption fine structure spectroscopy. This reaction is
      important as a basis of NOx reduction reactions on platinum-group metal surfaces.
      Atomic nitrogen layers on Rh(111) were titrated with NO at various temperatures.
      N2O is exclusively formed and desorbs into the gas phase below 350 K. The
      consumption rate of atomic nitrogen exhibits strange temperature dependence
      between 100 and 350 K; the reaction proceeds slower with increasing temperature.
      Reaction kinetics analyses and isotope-controlled experiments have revealed that
      the surface N atoms do not react with chemisorbed NO molecules but with NO dimers
      weakly bound on top of the chemisorbed layer, which play a role as an extrinsic
      precursor. The present results may support the possibility that NO dimers
      participate in various NO-related synthetic, biochemical, and surface reactions
      as an intermediate.

PMID- 17181189
TI  - Entangled photon absorption in an organic porphyrin dendrimer.
AB  - Two-photon absorption spectroscopy is an intensity dependent nonlinear effect
      related to the excitation of virtual intermediate states. The classical two
      photon absorption has an extremely low efficiency which is quantified by its
      cross-section (delta approximately 10(-48) cm4 s at 800 nm). To overcome this
      limitation, we demonstrate a novel effect of the two-photon absorption method
      utilizing the high degree of quantum optical correlation between photon pairs
      created by the process of spontaneous parametric downconversion. A large
      entangled two-photon absorption cross-section (delta(e) approximately 10(-17) cm2
      at 800 nm) was measured in an organic porphyrin dendrimer. We also discuss the
      nonmonotonic behavior of variation of the entangled two-photon absorption cross
      section by controlling the entanglement time. This novel effect may open new
      avenues for ultrasensitive detection in chemical and biological systems. TPA
      spectroscopy has been considered as a powerful tool in physics, chemistry, and
      biology. The inherent nonlinear process of the classical TPA is distinguishable
      from the single photon absorption (SPA) linear process. Although the benefits of
      greater penetration depth and better control and reduction of scattering, the TPA
      spectroscopy has been restricted by the necessity of a high power optical source
      due to the low efficiency of the TPA effect. The use of entangled photons from a
      correlated source for the purpose of the two-photon effect is promising in this
      regard as one may obtain two-photon effects with very small numbers of photons.

PMID- 17181190
TI  - Oxidic or metallic palladium: which is the active phase in pd-catalyzed aerobic
      alcohol oxidation?
AB  - In situ X-ray absorption spectroscopy combined with on-line catalytic
      measurements using FT-IR spectroscopy unequivocally identified that metallic
      palladium is the more active phase in the aerobic oxidation of benzyl alcohol
      than palladium oxide. The aerobic oxidation of benzyl alcohol in cyclohexane at
      50 degrees C was low over oxidized 0.5%Pd/Al2O3 and 5%Pd/Al2O3 catalysts. XANES
      and EXAFS showed that the catalysts in the as-received state were almost fully
      oxidized and no reduction of the palladium constituent was observed during time
      on-stream. After in situ reduction by hydrogen-saturated cyclohexane, the
      catalysts were much more active (over 50 times) than before reduction. Both XANES
      and EXAFS uncovered that the palladium constituent was mainly in a reduced state
      under these conditions of high catalytic activity. This demonstrates that
      metallic palladium is the active phase for alcohol dehydrogenation.

PMID- 17181191
TI  - Aggregates of quadrupolar dyes: giant two-photon absorption from biexciton
      states.
AB  - A model for aggregates of quadrupolar (DAD or ADA) molecules is presented that
      relaxes the dipolar approximation for intermolecular electrostatic interactions.
      New effects, including the appearance of bound biexcitons in clusters of nonpolar
      molecules, are predicted with interesting and unforeseen consequences on the
      material properties. Specifically, we show that the large two-photon absorption
      cross-section, typical of quadrupolar chromophores, can be further amplified by
      orders of magnitude as a result of aggregation.

PMID- 17181192
TI  - Diffusion and viscosity in a crowded environment: from nano- to macroscale.
AB  - Although water is the chief component of living cells, food, and personal care
      products, the supramolecular components make their viscosity larger than that of
      water by several orders of magnitude. Using fluorescence correlation spectroscopy
      (FCS), photon correlation spectroscopy (PCS), NMR, and rheology data, we show how
      the viscosity changes from the value for water at the molecular scale to the
      large macroviscosity. We determined the viscosity experienced by nanoprobes (of
      sizes from 0.28 to 190 nm) in aqueous micellar solution of hexaethylene-glycol
      monododecyl-ether (in a range of concentration from 0.1% w/w to 35% w/w) and
      identified a clear crossover at the length scale of 17 +/- 2 nm (slightly larger
      than persistence length of micelles) at which viscosity acquires its macroscopic
      value. The sharp dependence of the viscosity coefficients on the size of the
      probe in the nanoregime has important consequences for diffusion-limited
      reactions in crowded environments (e.g., living cells).

PMID- 17181193
TI  - Experimental anion affinities for the air/water interface.
AB  - Anion affinities, gammaX-, for the aerial interface of aqueous (Br- + NO3- + I- +
      SCN- + BF4- + ClO4-) solutions are determined by electrospray ionization mass
      spectrometry. The composition of the ions ejected from the surface of fissioning
      nanodroplets shows that gammaX- increase (decrease) exponentially with anionic
      radii, aX-(dehydration free energies, dGX-), and selectively respond to the
      presence of surfactants. BF4-, the least hydrated and polarizable anion of the
      set, has one of the largest gammaX- values. Non-ionic surfactants decrease gammaI
      and gammaSCN- but increase gammaBF4-. Cetyltrimethyl ammonium markedly enhances
      the gammaX- of smaller anions. A similar but weaker effect is observed upon
      lowering the pH of the bulk solutions from 8.2 to 3.0. Dodecyl sulfate has a
      negligible effect on gammaX-. Considering that (i) universal many-body
      electrodynamic interactions will progressively stabilize the interfacial layer as
      its dielectric permittivity falls relative to that of the bulk solution and (ii)
      water permittivity is uniformly depressed by increasing concentrations of these
      anions, we infer that the observed Hofmeister correlation, ln gammaX- infinity -
      dGX-, is consistent with the optimal depression of the permittivity of the drier
      interfacial layer by the least hydrated ions. Interfacial ion-ion interactions
      can significantly influence gammaX- in environmental aqueous media.

PMID- 17181194
TI  - Functionalization of titanium oxide surfaces by means of poly(alkyl
      phosphonates).
AB  - The use of a multiple attachment sites strategy is considered in order to improve
      the stability of monomolecular adlayers. The hypothesis was tested in the case of
      PEG-ylated compounds carrying phosphonate groups, known for their affinity toward
      titanium oxide surfaces. As a result, a new class of co- and terpolymers were
      synthesized by free-radical polymerization of three different monomers:
      dialkyl(methacryloyloxyalkyl)phosphonates, PEG methyl ether methacrylate, and/or
      butyl methacrylate monomers. Adlayers were formed following a simple dip-and
      rinse protocol using diluted aqueous polymer solutions and were characterized by
      evaluating their thicknesses with variable angle spectroscopic ellipsometry
      (VASE) and their elemental compositions with X-ray photoelectron spectroscopy
      (XPS). The same techniques were used to determine changes of the adlayer as a
      function of exposure to electrolytes at different pH values and to monitor
      nonspecific protein adsorption upon serum exposures. The results indicated that
      the poly(alkyl-phosphonate)-based adlayers combine multiple site attachment of
      phosphonic groups and presentation of PEG side chains to the aqueous environment,
      resulting in both improved stability over a wide pH range in comparison to the
      tested reference surfaces and excellent resistance to protein adsorption when
      exposed to full human serum.

PMID- 17181195
TI  - Volatile diffusional character of cytoplasm.
AB  - The fluctuating extracellular environment of microbial organisms influences
      diffusional mobility of macromolecules in the cytoplasm. This effect may be
      measured experimentally on the one hand by directly tracking the trajectories of
      individual macromolecules. We discuss how it may also be indirectly estimated
      from fluctuations in the amount of cytoplasmic water and from the varying
      patterns of protein expression seen in 2d gel analysis.

PMID- 17181196
TI  - Structural investigation of the confinement of finite amounts of trehalose in
      water-containing sodium Bis(2-ethylhexyl)sulfosuccinate reversed micelles.
AB  - The structural effect of trehalose confined in water-containing sodium bis(2
      ethylhexyl)sulfosuccinate (AOT) reversed micelles at water to AOT molar ratio W =
      5 and 10 as a function of the trehalose to AOT molar ratio T (0 < T < 0.1) has
      been investigated by small-angle neutron scattering (SANS). SANS data analysis is
      consistent with the hypothesis that trehalose is encapsulated within the quite
      spherical hydrophilic micellar cores of water-containing reversed micelles,
      causing an increase of the aggregate size and a decrease of the polydispersion.
      Moreover, SANS results suggest that the trehalose confinement in water-containing
      reversed micelles involves marked changes on the molecular packing of the water
      containing micellar cores. In particular, according to the obtained findings, we
      can hypothesize the intercalation of the trehalose molecules between the polar
      surfactant headgroups. The preferential solubilization in this specific
      nanodomain could explain the trehalose capability to prevent, upon dehydration,
      the transition to a gel phase, hindering serious damage to biostructures.

PMID- 17181197
TI  - Time-resolved photoluminescence characteristics of subnanometer ZnO clusters
      confined in the micropores of zeolites.
AB  - Subnanometric ZnO clusters confined in different micropore zeolites are studied
      by steady-state and nanosecond time-resolved photoluminescence (PL) spectroscopy.
      The microsecond-scale lifetime is observed at room temperature for ZnO clusters
      confined in zeolites, which is significantly different from that of
      macrocrystalline ZnO on the external surface of zeolites. The dependence of
      luminescence lifetime on the amount of ZnO in zeolites indicates that the
      electron-phonon interactions between the ZnO clusters and the zeolite host
      significantly affect the dynamic relaxation process of ZnO clusters. The long
      lifetime luminescence of ZnO clusters can be achieved by weakening the coupling
      of electronic transition to zeolites host phonons. The similar long-lived
      luminescence is obtained when dispersing ZnO clusters into the porous SiO2. It is
      suggested that encapsulating the semiconductor cluster in the porous support is a
      possible way to inhibit or to retard the electron-hole recombination.

PMID- 17181198
TI  - Nanoparticle-assembled capsule synthesis: formation of colloidal polyamine-salt
      intermediates.
AB  - There is current interest in developing new synthesis strategies for
      multifunctional hollow spheres with tunable structural properties that would be
      useful in encapsulation and controlled release applications. A new route was
      reported recently, in which the sequential reaction of polyamines, multivalent
      anions, and charged nanoparticles leads to the formation of polymer-filled and
      water-filled organic/inorganic micron-sized structures known as nanoparticle
      assembled capsules. This technique is unique among other capsule preparation
      routes, as it allows the rapid and scalable formation of robust shells at room
      temperature, in near-neutral water, and with readily available precursors. This
      nanoparticle assembly synthesis route involves two steps: the formation of
      polymer aggregates and the subsequent deposition of particles around the
      aggregates. The purpose of this paper is to understand in greater detail the
      noncovalent chemistry of the polymer-salt aggregation step. With poly(allylamine
      hydrochloride) (PAH) as the model polymer, aggregate formation was investigated
      as a function of charge ratio, pH, and time through dynamic light scattering,
      electrophoretic mobility measurements, chloride ion measurements, and optical
      microscopy. PAH formed aggregates by the cross-linking action of divalent and
      higher-valent anions above a critical charge ratio and in a pH range defined by
      the pKa values of PAH and the anion. The aggregates grew in size through
      coalescence and with growth rates that depended on their surface charge.
      Controlling polymer aggregate growth provided a direct and simple means to adjust
      the size of the resultant capsule materials.

PMID- 17181199
TI  - Solvent quality changes the structure of G8 PAMAM dendrimer, a disagreement with
      some experimental interpretations.
AB  - We have performed approximately 20-40 ns of molecular dynamics (MD) simulations
      for the generation 8 PAMAM dendrimer in explicit water under varying pH
      conditions to study the structure of the dendrimer (approximately 156,738 atoms
      at low pH). This is the first report of such a long MD simulation of a larger
      generation PAMAM dendrimer including the effect of salt and counterions with
      explicit water molecules. We find that changing the pH from a high value
      (approximately 12) to a low value (approximately 3) changes the radius of
      gyration from Rg = 37.8 to 43.1 A (increasing by 13%). We also find significant
      back-folding of the primary amines and a large amount of water penetration inside
      the polymer. The increase in size with decrease in pH is consistent with our
      earlier studies on G3-G6 and agrees with the Monte Carlo theory by Welch and
      Muthukumar of G8 (Macromolecules, 1998, 31, 5892) and the experiments on G5 and
      G8 PAMAM dendrimer by Topp et al. (Macromolecules, 1999, 32, 7232). However,
      these results disagree dramatically with the interpretations of SANS experiments
      of G8 PAMAM dendrimers by Nisato et al. (Macromolecules, 2000, 33, 4172) who
      observe no change in the size of the dendrimer with variations of solution pH and
      ionic strength. We assume that the disagreement might arise from neglecting
      nonspherical shape, penetration of water and ions into the core, and aggregation,
      all of which might depend on pH.

PMID- 17181200
TI  - Modified rare earth semiconductor oxide as a new nucleotide probe.
AB  - Recent rapid developments in biological analysis, medical diagnosis,
      pharmaceutical industry, and environmental control fuel the urgent need for
      recognition of particular DNA sequences from samples. Currently, DNA detection
      techniques use radiochemical, enzymatic, fluorescent, or electrochemiluminescent
      methods; however, these techniques require costly labeled DNA and highly skilled
      and cumbersome procedure, which prohibit any in-situ monitoring. Here, we report
      that hybridization of surface-immobilized single-stranded oligonucleotide on
      praseodymium oxide (evaluated as a biosensor surface for the first time) with
      complimentary strands in solution provokes a significant shift of electrical
      impedance curve. This shift is attributed to a change in electrical
      characteristics through modification of surface charge of the underlying modified
      praseodymium oxide upon hybridization with the complementary oligonucelotide
      strand. On the other hand, using a noncomplementary single strand in solution
      does not create an equivalent change in the impedance value. This result clearly
      suggests that a new and simple electrochemical technique based on the change in
      electrical properties of the modified praseodymium oxide semiconductor surface
      upon recognition and transduction of a biological event without using labeled
      species is revealed.

PMID- 17181201
TI  - Phenylthiophene-dipicolinic acid-based emitters with strong solution blue and
      solid state green emission.
AB  - The synthesis and characterization of highly efficient blue emitting phenyl
      thiophene compounds derivatized with dipicolinic acid bis(diethylamide) and
      dipicolinic acid diethyl ester 1, 2, and 3 are reported. Quantum yields were
      determined to be between 97% and 76% in methanol and 99% and 49% in toluene
      solution. The solvent dependences of the solution luminescence behavior are
      discussed in terms of solvent refractive index and dielectric constant as well as
      hydrogen-bonding capability. Luminescence is also observed in the solid state for
      the three compounds. A bathochromic shift in the emission wavelength is
      accompanied by solid-state quantum yields between 29% and 4%. HOMO and LUMO
      energies, in the range -5.55 to -5.71 eV and -2.20 to -2.48 eV, respectively,
      were determined experimentally from cyclic voltammetry and absorption
      spectroscopy experiments. The electrochemical characterization revealed that
      cyclic voltammetry can be utilized to deposit thin films of 3. An X-ray quality
      single crystal of 1 was isolated. This compound crystallizes in the monoclinic
      space group P21/c with cell parameters a = 15.224(3) A, b = 8.9383(18) A, c =
      17.234(3) A, beta =114.36(3) degrees, and V = 2136.4(7) A3. Appreciable solid
      state interactions in the form of pi-pi or S-S short contacts are not present,
      only weaker C-H...pi. A large torsion angle of 30.28 degrees between the phenyl
      and thiophene moieties and a small torsion angle of -3.37 degrees between the
      pyridine and the thiophene moieties are seen.

PMID- 17181202
TI  - Microenvironment in the corona region of triblock copolymer micelles: temperature
      dependent solvation and rotational relaxation dynamics of coumarin dyes.
AB  - Dynamic Stokes' shift and fluorescence anisotropy measurements using coumarin-153
      (C153) and coumarin-151 (C151) as the fluorescence probes have been carried out
      in aqueous poly(ethylene oxide)20-poly(propylene oxide)70-poly(ethylene oxide)20
      (P123) and poly(ethylene oxide)100-poly(propylene oxide)70-poly(ethylene
      oxide)100 (F127) block copolymer micelles with an aim to understand the water
      structures and dynamics in the micellar corona region. It has been established
      that the probes reside in the micellar corona region. It is indicated that the
      corona regions of P123 and F127 micelles are relatively less hydrated than the
      Palisade layers of neutral micelles like Triton-X-100 and Brij-35. From the
      appraisal of total Stokes' shift values for the probes in the two block copolymer
      micelles, it is inferred that the F127 micelle is more hydrated than the P123
      micelle. It is observed that the dynamic Stokes' shift values for both of the
      probes remain more or less similar at all the temperatures studied in the P123
      micelle. For C153 in F127, however, the observed Stokes' shift is seen to
      decrease quite sharply with temperature, though it remains quite similar for
      C151. Moreover, the fraction of the unobserved initial dynamic Stokes' shift is
      appreciably higher for both the probes in the F127 micelle compared to that in
      P123. Over the studied temperature range of 293-313 K, the spectral shift
      correlation function is described adequately by a bi-exponential function.
      Rotational relaxation times for C153 in both the micelles show a kind of
      transition at around 303 K. These results have been rationalized assuming
      collapse of the poly(ethylene oxide) (PEO) blocks and formation of water clusters
      in the corona region due to dehydration of poly(ethylene oxide) blocks with an
      increase in temperature. A dissimilar probe location has been inferred for the
      differences in the results with C153 and C151 probes in F127. Comparison of the
      microviscosity and the hydration of the block copolymer micelles has also been
      made with those of the other commonly used neutral micelles, for a better
      understanding of the results in the block copolymer micelles.

PMID- 17181203
TI  - Electrochemistry of conductive polymers 39. Contacts between conducting polymers
      and noble metal nanoparticles studied by current-sensing atomic force microscopy.
AB  - Electrical properties of contacts formed between conducting polymers and noble
      metal nanoparticles have been examined using current-sensing atomic force
      microscopy (CS-AFM). Contacts formed between electrochemically prepared pi
      conjugated polymer films such as polypyrrole (PPy), poly(3-methylthiophene)
      (P3MeT), as well as poly(3,4-ethylenedioxythiophene) (PEDOT) and noble metal
      nanoparticles including platinum (Pt), gold (Au), and silver (Ag) have been
      examined. The Pt nanoparticles were electrochemically deposited on a pre-coated
      PPy film surface by reducing a platinum precursor (PtCl62-) at a constant
      potential. Both current and scanning electron microscopic images of the film
      showed the presence of Pt islands. The Au and Ag nanoparticles were dispersed on
      the P3MeT and PEDOT film surfaces simply by dipping the polymer films into
      colloid solutions containing Au or Ag particles for specified periods (5 to
      approximately 10 min). The deposition of Au or Ag particles resulted from either
      their physical adsorption or chemical bonding between particles and the polymer
      surface depending on the polymer. When compared with PPy, P3MeT and PEDOT showed
      a stronger binding to Au or Ag nanoparticles when dipped in their colloidal
      solutions for the same period. This indicates that Au and Ag particles are
      predominantly linked with the sulfur atoms via chemical bonding. Of the two,
      PEDOT was more conductive at the sites where the particles are connected to the
      polymer. It appears that PEDOT has better aligned sulfur atoms on the surface and
      is strongly bonded to Au and Ag nanoparticles due to their strong affinity to
      gold and silver. The current-voltage curves obtained at the metal islands
      demonstrate that the contacts between these metal islands and polymers are ohmic.

PMID- 17181204
TI  - Dielectrophoresis of an inhomogeneous colloidal particle under an inhomogeneous
      field: a first-principles approach.
AB  - In reality, colloidal particles often possess an arbitrary inhomogeneity profile.
      We present a first-principles approach to dielectrophoresis of such an
      inhomogeneous colloidal particle under an inhomogeneous field of an oscillating
      electric dipole moment. For numerical simulations, we treat the inhomogeneous
      particle as a specific graded one with a physically motivated dielectric model
      and conductivity profile. We find that both multipolar interactions and spatial
      fluctuations inside the particle can affect the dielectrophoretic spectrum of the
      particle significantly.

PMID- 17181205
TI  - Raman spectroscopic studies of terthiophenes for molecular electronics.
AB  - The effect of thiol and selenol functionalization on the vibrational spectra and
      photochemical stability of terthiophene based molecular wires was investigated
      using surface-enhanced Raman scattering (SERS). The molecules were found to
      exhibit markedly different properties at the silver surface of the SERS
      substrate, despite having almost identical Raman spectra in solution and in the
      solid state. In contrast to terthiophene (3T), the bisthiolterthiophene (T3) and
      biselenol-terthiophene (Se3) molecules were stable against photoinduced
      structural changes when adsorbed to the metal surface at low concentrations. This
      indicates that the strong bonds to the silver surface, via S or Se terminal
      atoms, leads to a rapid decay of photoexcited states. Comparison with ab initio
      calculations shows that both T3 and Se3 bind with only one of the functional
      groups to the Ag surface.

PMID- 17181206
TI  - Atomic and electronic structures of fluorinated BN nanotubes: computational
      study.
AB  - The atomic and electronic structures of fluorinated BN nanotubes (BNNTs) were
      investigated by generalized gradient approximation (GGA) density functional
      theory (DFT). The reaction energies of F2 with pristine single-walled BNNTs to
      form fluorinated BNNTs are exothermic up to 50% coverage. At lower F coverages
      (below 50%), fluorines prefer external attachments to boron atoms and stay as far
      away as possible. At 50% F coverage, fluorines favor attachment to all the boron
      atoms of the outer surface energetically. Such preferable fluorination patterns
      and highly exothermic reaction energies hold true for double-walled (and
      multiwalled) BNNTs when the outer tube surface is considered. Fluorination
      transforms BNNTs into p-type semiconductors at low F coverages, while high F
      coverages convert BNNTs into p-type conductors. Therefore, the electronic and
      transport properties of BNNTs can be engineered by fluorination, and this
      provides potential applications for fluorinated BNNTs in nanoelectronics.

PMID- 17181207
TI  - Crystal structure, Raman spectroscopy, and ab initio calculations of a new
      bialkali alanate K2LiAlH6.
AB  - A new bialkali alanate K2LiAlH6 was synthesized at 320-330 degrees C and 100-700
      bar. It was structurally characterized by powder X-ray diffraction. It
      crystallizes in space group R3m (No. 166) with unit cell parameters a =
      5.62068(8) and c = 27.3986(6) A. The Li and K cation sites are mutually
      exclusive, and Rietveld refinement finds no cation mixing. First-principles total
      energy calculations were performed for nine competing database structures of the
      stoichiometry A2BCX6, taken from fluoride and oxide compounds in the Inorganic
      Crystal Structure Database (ICSD). The relaxed structures were compared via their
      total energies and their agreement with experimental diffraction spectra. Two
      database structures K2LiAlF6 (R3m) and Cs2NaAlF6 (C2/m) were found to have the
      lowest total energies, but with the Rietveld method the K2LiAlF6 structure type
      was shown to be the most favorable. Ab initio total energy calculations support
      the validity of the structure determination. First-principles calculations also
      indicate that cation mixing is energetically unfavorable. Hydride properties such
      as plateau pressure are therefore more difficult to manipulate through alloying
      in this class of compounds.

PMID- 17181208
TI  - Structure and dynamics of L-selenomethionine in the solid state.
AB  - L-selenomethionine 1 crystallizes in P2(1) space group with two molecules in the
      asymmetric unit. Solid-state NMR spectroscopy is used for searching of structure
      and dynamics of 1 in the crystal lattice. The distinct molecular motion of side
      chains for A and B molecules of 1 is apparent from measurements of relaxation
      parameters (1H 1rho, 13C T1) and analysis of CSA data (2D-PASS experiment). The
      13C delta(ii) and 77Se delta(ii) parameters are correlated with theoretical
      shielding parameters obtained by means DFT GIAO calculations. Attempt to explain
      the mechanism of phase transition of crystals of 1 at 313K is presented.

PMID- 17181209
TI  - Shape control of single crystalline bismuth nanostructures.
AB  - A synthesis approach for shape control of single crystalline Bi nanostructures
      has been developed. By controlling the molar ratio of PVP and Bi in a polyol
      process, Bi nanocubes with an edge length of approximately 60-80 nm, triangular
      nanoplates with an edge length of 200-500 nm, and nanospheres with an average
      diameter of 75 nm have been successfully synthesized. In the same synthetic
      process, Bi nanobelts with lengths of up to 80 microm and widths of up to 0.6
      microm were synthesized in large quantities by introducing a trace amount of Fe3+
      species into the reaction system. These single crystalline nanostructure Bi
      materials are expected to find potential applications in a variety of areas
      including high efficiency thermoelectric devices.

PMID- 17181210
TI  - Photoluminescence response of terbium-exchanged MFI-type materials to Si/Al
      ratio, texture, and hydration state.
AB  - Terbium-exchanged MFI zeolite type materials, i.e., microporous-mesoporous
      Zeotile-1 with the Si/Al ratio in the range 33-200, Zeogrid with the Si/Al ratio
      of 75, and nanocrystalline MFI with the Si/Al ratio of 75, were prepared via an
      ion exchange procedure. All of these zeolites were investigated by means of time
      resolved photoluminescence techniques in various hydration states: as-synthesized
      (hydrated), calcined (heated at 450 degrees C in air), and rehydrated (after a
      six-month exposure to the atmospheric moisture). The photoluminescence decays and
      spectra were analyzed by discrete exponential fitting, distribution lifetimes
      analysis, and area-normalized time-resolved photoluminescence spectra. The
      results sustained a single average terbium species coordinated to both water
      molecules and framework oxygens in the hydrated zeolites. The framework
      contribution increased with the Si/Al ratio in Zeotile-1 and was greatest for the
      nanocrystalline MFI zeolite. For the calcined Zeotile-1 and Zeogrid, two main
      terbium species of different environments were found. For the nanocrystalline
      Tb3+-MFI, a distinct number of species could not be inferred, indicating a more
      heterogeneous distribution. Rehydration further differentiated among the Tb3+
      exchanged zeolites. Photoluminescence line shape and decay of Tb3+-Zeotile-1 were
      between those of the hydrated and calcined states indicating a slow rehydration
      rate in contrast with the photoluminescence properties of Tb3+-MFI, which fully
      recovered the values of the hydrated state. Tb3+-Zeogrid presented an
      intermediate case: while the PL line shape was fully restored to that measured
      for the hydrated sample, the decay was still longer than that measured with the
      hydrated sample. Terbium photoluminescence response related to zeolite texture,
      Si/Al ratio, and hydration state suggest different sitting and location of
      terbium in Zeotile-1, Zeogrid, and nanocrystalline MFI materials. In mesoporous
      Zeotile-1 and Zeogrid, the results sustained two types of terbium sites: one on
      the internal surface of mesopores, the other inside the pores, while for the
      nanocrystalline MFI, terbium sites inside the pores predominate.

PMID- 17181211
TI  - A comparison between photon counting histogram and fluorescence intensity
      distribution analysis.
AB  - Photon counting histogram (PCH) and fluorescence intensity distribution analysis
      (FIDA) are two methods that were developed independently but reported almost
      simultaneously. Both of them have been successfully applied to fluorescence
      fluctuation spectroscopy (FFS). Though publications have indicated that they are
      theoretically equivalent, they are still commonly considered as different
      methods, especially in their ways to treat the point spread functions (PSFs). In
      this paper, the two methods are examined in detail for a direct comparison. After
      a direct proof of the theoretical equivalence, the authors further point out that
      PCH and FIDA are completely equivalent in the way of modeling PSFs; that is, any
      modeling approach developed from one of them can always be applied to the other.
      It is also demonstrated that simplified FIDA and PCH formulas in the form of
      power series can be applied for fast and precise numerical calculations. The two
      methods are also compared for their merits in the calculation efficiency.

PMID- 17181212
TI  - Seeded-growth approach to fabrication of silver nanoparticle films on silicon for
      electrochemical ATR surface-enhanced IR absorption spectroscopy.
AB  - Ag nanoparticle films (simplified as nanofilms hereafter) on Si for
      electrochemical ATR surface enhanced IR absorption spectroscopy (ATR-SEIRAS) have
      been successfully fabricated by using chemical deposition, which incorporates
      initial embedding of Ag seeds on the reflecting plane of an ATR Si prism and
      subsequent chemical plating of conductive and SEIRA-active Ag nanofilms. Two
      alternative methods for embedding initial Ag seeds have been developed: one is
      based on self-assembly of Ag colloids on an aminosilanized Si surface, whereas
      the other the reduction of Ag+ in a HF-containing solution. A modified silver
      mirror reaction was employed for further growth of Ag seeds into Ag nanofilm
      electrodes with a theoretically average thickness of 40-50 nm. Both Ag seeds and
      as-deposited Ag nanofilms display island structure morphologies facilitating
      SEIRA, as revealed by AFM imaging. The cyclic voltammetric feature of the as
      prepared Ag nanofilm electrodes is close to that of a polycrystalline bulk Ag
      electrode. With thiocyanate as a surface probe, enhancement factors of ca. 50-80
      were estimated for the as-deposited Ag nanofilms as compared to a mechanically
      polished Ag electrode in the conventional IRAS after reasonable calibration of
      surface roughness factor, incident angles, surface coverage, and polarization
      states. As a preliminary example for extended application, the pyridine
      adsorption configuration at an as-deposited Ag electrode was re-examined by ATR
      SEIRAS. The results revealed that pyridine molecules are bound via N end to the
      Ag electrode with its ring plane perpendicular or slightly tilted to the local
      surface without rotating its C2 axis about the surface normal, consistent with
      the conclusion drawn by SERS in the literature.

PMID- 17181213
TI  - Swelling kinetics of poly(N-isopropylacrylamide) minigels.
AB  - We synthesize poly(N-isopropylacrylamide) (PNIPAM) gels with different sizes in
      the micrometer scale by a slight variation of a recent emulsion polymerization
      method (ref 1). The procedure is different than that typically used for obtaining
      macroscopic PNIPAM hydrogels. The resultant minigel suspension is polydisperse
      thus allowing the swelling kinetics for different gel sizes to be studied; we do
      so at temperatures below the volume-transition temperature by wetting with water
      previously dried particles. The resultant swelling is followed by optical video
      microscopy. We find that the characteristic swelling time scales with the inverse
      of the particle dimension squared, in agreement with theoretical predictions (ref
      2). The proportionality constant is the network diffusion coefficient D, which
      for the minigels under consideration appears to be in between that of PNIPAM
      macrogels and the self-diffusion coefficient of water.

PMID- 17181214
TI  - Mechanistic investigations of PEG-directed assembly of one-dimensional ZnO
      nanostructures.
AB  - Mechanistic investigation on spherical assembly of the unique one-dimensional ZnO
      nanorods, solid nanocones, or hollow prisms with the closed -c end, directed by
      poly ethylene glycol (PEG) with different molecular weights, has been carried out
      using spectroscopic methods. The single crystalline ZnO nanoprisms, hollow along
      the c axis but closed at the -c end, aggregate to urchin-type globules in the
      microscale when PEG 2000 is used as directing reagent, while spherical aggregates
      of single crystalline ZnO nanocones are obtained under the direction of PEG 200.
      Studies reveal that both the PEG molecules aggregate to globules by interacting
      with zinc species in suitable solvents and englobe the zinc species. By the short
      time of ultrasonic pretreatment on the solution, a kind of flagellum structure is
      induced around the globules, in long tubular shapes for PEG 2000 but as shorter
      wedges for PEG 200. The globules with flagellums are templates for the assembly
      of the ZnO nanotubes or ZnO nanocones in the hydrothermal treatment. The tiny ZnO
      crystallites, produced in the hydrothermal process, stack to the templates and
      amalgamate to single crystalline nanotubes or nanocones, similar to the oriented
      attachment mechanism. The PEG 2000 template is included in the ZnO cavity of
      nanotubes, while PEG 200 is excluded from the ZnO nanocones due to the different
      intertwist properties between the two PEG molecules. Both the urchin-type
      assemblies, possessing the same external crystalline plane, compose a isotropic
      powder and emit very strong yellow light, centered at approximately 2.1 eV, under
      the excitation of the He-Cd laser at 325 nm, which has been correlated to the
      specific crystal plane. The special powders will be easily coated onto any type
      of surface for the decoration of a large area of surfaces for future
      applications.

PMID- 17181215
TI  - Phase transformations in bulk nanostructured potassium niobiosilicate glasses.
AB  - In potassium niobiosilicate (KNS) glasses, nanostructuring can be driven and
      controlled by thermal treatments at the glass transition temperature and/or by
      modulation of the chemical composition. The tight relationship between
      nanostructure and nonlinear optical properties suggests these bulk nanomaterials
      as an appealing route to nanophotonics. The focus of this paper is placed on
      assessing the phase transformations which occur in these materials upon annealing
      at the glass transition temperature and subsequent heating. High-temperature
      resolved X-ray diffraction (HTXRD) and high-resolution transmission electron
      microscopy (HRTEM) experiments are integrated with previously published results
      for in-depth insight. It will be shown that nanostructuring evolves from
      nucleation of niobium-rich nanocrystals, which are up to 20 nm large, uniformly
      distributed in the matrix bulk, and metastable. Formation kinetics as well as
      phase transformation of the nanocrystals are determined by the glass composition.
      Depending on it, nanocrystal nucleation can be preceded or not by phase
      separation, and the nanocrystals' phase transition can be of first or second
      order.

PMID- 17181216
TI  - Direct synthesis of nanowires with anatase and TiO2-B structures at near ambient
      conditions.
AB  - In this study, we present a new approach toward titanium oxide nanowires. In this
      approach, the growth formation of the wires sets in at a temperature as low as 40
      degrees C under ambient pressure. Moreover, we provide evidence that nanowires
      with distinctive TiO2-anatase and TiO2-B structures can be directly produced
      without further thermal treatment using controlled reaction conditions.

PMID- 17181217
TI  - Structure and dynamics of perfluoroalkane/beta-cyclodextrin inclusion compounds
      as studied by solid-state 19F MAS and 1H -->19F CP/MAS NMR spectroscopy.
AB  - The molecular structure and dynamics of novel inclusion compounds (ICs)
      consisting of n-perfluoroalkane (PFA) guests and beta-cyclodextrin (beta-CD) host
      (PFA/beta-CD) have been investigated using 19F magic angle spinning (MAS) and 1H-
      >19F cross polarization (CP)/MAS NMR spectroscopy with the aid of thermal
      analyses, FT-IR spectroscopy, and X-ray diffraction method. The ICs of C9F20/beta
      CD and C20F42/beta-CD were successfully obtained as precipitates from mixtures of
      respective PFAs and saturated aqueous solution of beta-CD. The wide-angle X-ray
      diffraction (WAXD) revealed that C9F20/beta-CD forms a channel-type crystallite,
      while C20F42/beta-CD is nearly amorphous at room temperature. The structural
      orders in both ICs increase at elevated temperatures. The 19F NMR signals
      obtained by the direct polarization (DP) method for PFA/beta-CD are resonated at
      higher frequencies than those for original PFA. This can be ascribed to the lower
      dielectric environment of the beta-CD cavity. Above 80 degrees C, 1H-->19F CP/MAS
      NMR technique revealed that C9F20 molecules undergo vigorous molecular motion and
      partly come out of the beta-CD channel. However, the guests hardly degrade or
      evaporate unless the host is pyrolytically decomposed above ca. 300 degrees C.
      The spin-lattice relaxation times in the laboratory frame for 19F (T1F) are
      almost identical for all the fluorines in PFA/beta-CD at each temperature, while
      significantly different values were observed for fluorines in neat PFA. This
      indicates that effective intramolecular spin diffusion occurs within a PFA
      molecule included in beta-CD.

PMID- 17181218
TI  - Molecular dynamics simulation study of the structural characteristics of water
      molecules confined in functionalized carbon nanotubes.
AB  - Molecular dynamics (MD) simulations were performed to study the structural
      properties of water molecules confined in functionalized carbon nanotubes (CNTs).
      Four CNTs, two armchair-type (6, 6), (7, 7) and two zigzag-type (10, 0), (12, 0)
      CNTs, representing different helicities and different diameters, were chosen and
      functionalized at their open ends by the hydrophilic -COOH and the hydrophobic 
      CH3 groups. The structural properties of water molecules inside the
      functionalized CNTs, including the orientation distributions of dipole moment and
      O-H bonds, the length of the single-file water chain, and the average number of
      hydrogen bonds, were analyzed during a process of simulations. MD simulation
      results in this work showed that the -CH3 functional groups exert little special
      effects on the structural properties of water molecules. It is mainly due to the
      relatively small size of the -CH3 group and its hydrophobic nature, which is
      consistent with hydrophobic CNTs. For CNTs functionalized by -COOH groups, the
      configurations of -COOH groups, incurvature or excurvature, determine whether
      water molecules can enter the CNTs. The incurvature or excurvature configurations
      of -COOH groups are the results of synergy effects of the CNTs' helicity and
      diameter and control the flow direction of water molecules in CNTs.

PMID- 17181219
TI  - Mg1.8La0.2Ni-xNi nanocomposites for electrochemical hydrogen storage.
AB  - Mg1.8La0.2Ni hydrogen storage alloy was ball-milled with Ni powder, leading to
      the formation of a nanocrystalline and amorphous microstructure with particle
      sizes less than 50 nm in diameter. Each sample was examined by transmission
      electron microscopy (TEM), energy-dispersive spectroscopy (EDS), and X-ray
      diffraction (XRD). This structure was beneficial for the reduction of
      electrochemical impedance, as well as significant improvement of its discharge
      capacity, cycle life, and rate capability for electrochemical hydrogen storage in
      an alkaline solution. When the molar ratio (x) of Ni over Mg1.8La0.2Ni was equal
      to 2, the dehydriding capacity reached 2.55 wt % from electrochemical pressure
      temperature isotherms (P-C-T). It was in good agreement with its initial
      discharge capacity, 716 mA*h/[g of (Mg1.8La0.2Ni)], observed from the
      electrochemical charge and discharge process. After 50 cycles, its discharge
      capacity still reached 381 mA*h/[g of (Mg1.8La0.2Ni)]. Further results showed
      that this composite had a promising high rate capability. At the current density
      of 1200 mA/g its discharge capacity reached 48% of its initial capacity.

PMID- 17181220
TI  - Solute-solvent contact by intermolecular cross-relaxation. 2. The water-micelle
      interface and the micellar interior.
AB  - The intermolecular dipole-dipole cross-relaxation is measured between 19F nuclei
      of sodium perfluorooctanoate in micelles and 1H nuclei of the water solvent. The
      cross-relaxation rates for fluorines in the different moieties along the
      surfactant vary strongly by the resonance frequency in the investigated range of
      188-470 MHz. This frequency dependence indicates that the cross-relaxation
      between water and amphiphilic aggregates is not controlled solely by the fast
      local water dynamics but significantly contributed to by the long-range
      translational diffusion of water. The cross-relaxation rates, analyzed in the
      framework of a model (Nordstierna, L.; Yushmanov, P. V.; Furo, I. J. Chem. Phys.
      2006, 125, 074704), provide information about the dynamic retardation of water
      molecules by the micellar headgroup region and the location of the various
      moieties along the hydrophobic tail with respect to the water-micelle interface.
      Both intermolecular cross-relaxation and aggregation-induced 19F chemical shift
      changes indicate no direct water contact to fluorines except for those closest to
      the head group.

PMID- 17181221
TI  - Synthesis and characterization of mesoporous ceria with hierarchical
      nanoarchitecture controlled by amino acids.
AB  - In this work, we report the synthesis and characterization of mesoporous ceria
      with hierarchical nanoarchitectures controlled by amino acids. During the
      synthesis procedure, cerium oxalate precipitate was treated hydrothermally with
      different amino acids as crystallization modifiers, and hierarchically structured
      cerium oxalate precursors were obtained. Ceria can be produced after thermal
      decomposition of the cerium oxalate precursors. Structure and properties of the
      product were characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy, N2
      adsorption analysis, and X-ray photoelectron spectroscopy (XPS) methods. The
      results indicate that the mesoporous ceria with hierarchical nanoarchitectures
      are composed of nanosized ceria crystallites as building units and possess high
      surface area and high concentration of oxygen vacancy. Depending on different
      amino acids as the crystallization modifiers, the ceria exhibit different
      morphologies, such as dendritic aggregation of rods, dumbbells of nanorod arrays,
      or aggregated spheres. It is proposed that both the type of functional side
      groups and the length of the side groups of the amino acids influence the
      morphologies of the ceria. Meanwhile, the solvent and hydrothermal treatment
      temperatures also play important roles in the morphological control. The method
      reported in this work would be regarded as a general way to fabricate mesoporous
      metal oxides with hierarchical nanoarchitectures.

PMID- 17181222
TI  - In situ electrochemical fluorescence studies of PPV.
AB  - Conjugated phenylene-vinylene polymers are widely used in organic light-emitting
      and photovoltaic devices. The comprehension of the optical properties upon charge
      injection is of crucial importance for the improvement of such organoelectronic
      devices. The processes of electrochemical doping, electrolyte diffusion, and
      degradation have been studied by cyclic voltammetry and chronoamperometric
      methods. Kinetic studies by in situ fluorescence spectroscopy have been used for
      the determination of the mobility of charge carriers in the polymer making used
      of electrochemical Stern-Volmer analysis. The mobility of holes for MDMO-PPV
      measured by this method was 2.5 x 10(-7) cm2 V s(-1). Non-Faradic variations of
      the fluorescence after doping-dedoping cycles have been related to morphological
      changes in the polymeric layer. The evolution of the fluorescence obeys a first
      order kinetics law, similarly to the trend of the variation of volume during gel
      shrinking.

PMID- 17181223
TI  - Architecture of fiber network: from understanding to engineering of molecular
      gels.
AB  - A new approach of engineering of molecular gels was established on the basis of a
      nucleation-initiated network formation mechanism. A variety of gel network
      structures can be obtained by regulating the starting temperature of the sol-gel
      transition. This enables us to tune the network from the spherulitic domains
      pattern to the extensively interconnected fibrillar network. As the consequence
      of fibrous network structure turning, desirable rheological and other in-use
      properties of the materials can be obtained accordingly. This approach of micro
      /nanostructural fabrication may open up a new route for micro-/nanofunctional
      materials engineering in general.

PMID- 17181224
TI  - Hydrate kinetics study in the presence of nonaqueous liquid by nuclear magnetic
      resonance spectroscopy and imaging.
AB  - The dynamics of methane hydrate growth and decomposition were studied by nuclear
      magnetic resonance (NMR) spectroscopy and imaging (MRI). Three well-known large
      molecule guest substances (LMGS) were used as structure H hydrate formers: 2,2
      dimethylbutane (NH), methylcyclohexane (MCH), tert-butyl methyl ether (TBME). In
      addition, the impact of a non-hydrate former (n-heptane/nC7) was studied. The
      methane diffusion and hydrate growth were monitored by recording the 2H NMR
      spectra at 253 K and approximately 4.5 MPa for 20 h. The results revealed that
      methane diffuses faster in TBME and NH, slower in nC7, and slowest in MCH. The
      TBME system gives the fastest hydrate formation kinetics followed by NH, MCH, and
      nC7. The conversion of water into hydrate was also observed. The imaging study
      showed that TBME has a strong affinity toward ice, which is not the case for the
      NH and MCH systems. The degree of ice packing was also found to affect the LMGS
      distribution between ice particles. Highly packed ice increases the mass transfer
      resistance and hence limits the contact between LMGS and ice. It was also found
      that "temperature ramping" above the ice point improves the conversion
      significantly. Finally, hydrates were found to dissociate quickly within the
      first hour at atmospheric pressure and subsequently at a much slower rate.
      Methane dissolved in LMGS was also seen. The residual methane in hydrate phase
      and dissolved in LMGS phase explain the faster kinetics during hydrate re
      formation.

PMID- 17181225
TI  - Ab initio molecular dynamics study of 45S5 bioactive silicate glass.
AB  - Bioglass 45S5, the prototype of bioactive melt-quenched silicate glasses, was
      modeled by means of Car-Parrinello molecular dynamics (CPMD) simulations.
      Although long-range structural properties cannot be modeled by using this ab
      initio approach, the accuracy of CPMD simulations is exploited here to provide
      insight into the short-range structure and to analyze vibrational and electronic
      properties of this biomaterial. Detailed structural analysis in the short-range
      scale provided insight into the local environment of modifier Na and Ca ions: a
      possible key role of these cations in organizing the glass network by connecting
      different chains and fragments into specific, rather flexible geometries was
      proposed. The individual contributions of different species to the vibrational
      density of states were separated and discussed, allowing the identification of
      specific features in the vibrational spectrum, such as those related to phosphate
      groups. The components of the electronic density of states were also analyzed,
      enabling us to identify correlations between the electronic structure and the
      structural properties, such as the different bonding character of Si-O bonds
      involving bridging or nonbridging oxygen atoms.

PMID- 17181226
TI  - Structural feature and catalytic performance of Cu species distributed over TiO2
      nanotubes.
AB  - Copper oxide was deposited on tubular TiO2 via Cu2+ introduction into a titanate
      nanotube aggregate followed by calcination. The titanate has a layered structure
      allowing Cu intercalation and can readily transform into anatase TiO2 via
      calcination for condensation of the constituting layers. The activity of the
      tubular catalysts, with a Cu content of 2 wt %, in selective NO reduction with
      NH3 was compared with those of other 2 wt % Cu/TiO2 catalysts using TiO2
      nanoparticles as the support. The Cu species supported on the nanotubes showed a
      higher activity than those supported on the nanoparticles. X-ray absorption near
      edge structure (XANES) analysis showed that the Cu species on all the TiO2
      supports are in the +2 state. Extended X-ray absorption fine structure (EXAFS)
      investigations of these catalysts reflected higher degrees of CuO dispersion and
      Cu2+ dissolution into the TiO2 lattice for the tubular Cu/TiO2 catalysts. Absence
      of CuO bulk detection by a temperature-programmed reduction analysis for the
      tubular catalysts confirmed the high CuO-dispersion feature of the tubular
      catalysts. The dissolution of Cu2+ to form a CuxTi1-xO2 type of solid solution
      was improved by using an in-situ ion-intercalation method for Cu deposition on
      the nanotubes. A fraction as high as 40% for Cu2+ dissolution was obtained for
      the tubular catalysts while only 20% was obtained for the particulate catalysts.
      The CuxTi1-xO2 species were considered one form of the active sites on the
      Cu/TiO2 catalysts.

PMID- 17181227
TI  - Synthesis of hexagonal BaTa2O6 nanorods and influence of defects on the
      photocatalytic activity.
AB  - Hexagonal barium tantalate (BaTa2O6) nanorods were synthesized by a hydrothermal
      method based on the reaction of concentrated Ba(OH)2 solution and Ta2O5. BaTa2O6
      samples show a uniform cylindrical structure with diameters of 5-30 nm and the
      lengths of 50-200 nm. The formation of BaTa2O6 nanorods follows a dissolution
      recrystallization mechanism and is governed by hydrothermal temperature and time.
      BaTa2O6 nanorod samples prepared at 270 degrees C for 72 h have exhibited the
      highest photocatalytic activity in the degradation of Rhodamine B (RhB) in
      aqueous solution under UV radiation. Hydrogen-related defects were detected in
      BaTa2O6 nanorods, which originate from the oxygen octahedron. The number of
      defects was dependent on the hydrothermal temperature, and the photocatalytic
      activities of BaTa2O6 nanorods increase with the decrease of defect amounts. On
      the basis of the experiment results, the difference in photocatalytic activities
      for samples is mainly caused by lattice defects, which can act as inactivation
      centers.

PMID- 17181228
TI  - Mechanochemical synthesis and crystal structure of alpha'-AlD3 and alpha-AlD3.
AB  - AlD3 AlD3 was synthesized by ball milling of 3LiAlD4 + AlCl3. Planetary ball
      milling at room temperature resulted in a mixture of AlD3 (alpha and alpha') and
      Al in addition to LiCl, whereas cryomilling at 77 K resulted in only AlD3 and
      LiCl. The AlD3 obtained was a mixture of about 2/3alpha and 1/3alpha'. Alpha' was
      determined by powder neutron diffraction to take the beta-AlF3 structure with
      space group Cmcm and a = 6.470(3), b = 11.117(5), and c = 6.562(2) A. It is built
      up of corner-sharing AlD6 octahedra in an open structure with hexagonal holes of
      radius 3.9 A. Alpha' slowly decomposes during storage at 40 degrees C. Alpha-AlD3
      is also described by a corner-sharing AlD6 network but in a more dense ReO3-type
      arrangement. Both AlD3 modifications have slightly shorter Al-D distances
      compared to Na3AlD6, Na2LiAlD6, and K2NaAlH6.

PMID- 17181229
TI  - Dendrimer pattern formation in evaporating drops.
AB  - The redistribution of organic solutes during drop evaporation is a nanoscale self
      assembly process with relevance to technologies ranging from inkjet printing of
      organic displays to synthesis of biosmart interfaces for sensing and screening.
      We have used solutions of dendrimer molecules with incrementally varying terminal
      site chemistry to explore whether the condensed dendrimer patterns resulting from
      microdroplet evaporation sensitively depend on, and are characteristic of, the
      surface chemistry of the solute molecules. This hypothesis has been
      experimentally confirmed by comparing the behavior of microdroplets of G4, G4
      25%C12, and G4-50%C12 dendrimers dissolved in pentanol and deposited on mica
      substrates. For the dilute concentration studied here, the presence of
      periodically 'scalloped' dendrimer rings is ubiquitous. The instability
      wavelength of the scalloped rings is found to be proportional to the width of the
      ring, similar to observations of the rim instability in dewetting holes. The
      effect of dendrimer surface chemistry is obvious in the detailed structure of the
      self-assembled rings. G4 rings are diffuse and disordered with no evidence for
      layered growth. G4-25%C12 exhibits highly ordered ring structures and the onset
      of monomolecular terracing. G4-50%C12 exhibits highly periodic scallops and very
      distinct monomolecular height terraced growth of the rings with flat terraces and
      sharply defined steps. On the basis of these results, it is likely that the
      morphology of condensed molecule-based ring patterns formed by evaporation of
      microdroplets on surfaces can be used as a 'fingerprint' to identify, for
      example, solute molecule surface chemistry and concentration and function as a
      sensor for a variety of biochemical events.

PMID- 17181230
TI  - Dispersing and functionalizing multiwalled carbon nanotubes in TiO2 sol.
AB  - We report that oxidized multiwalled carbon nanotubes (MWCNTs) can be
      synchronously dispersed and functionalized in TiO2 sol via an in situ sol-gel
      process. Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy
      (XPS), Raman spectroscopy, and atomic force microscopy (AFM) were used to
      characterize the functionalized MWCNTs. The results revealed that the hydrolysis
      and condensation originated from Ti(OC4H9)4 molecules favor the dispersion of
      MWCNTs in as-prepared TiO2 sol. Based on the strong interaction between the
      oxidized MWCNTs and TiO2 sol during the in situ sol-gel process, MWCNT (core)
      TiOx (shell) tubular composites and TiO2 nanotubes can be obtained through
      filtrating, washing, and annealing of this kind of TiO2 sol containing
      functionalized MWCNTs, as revealed by TEM, XPS, Raman spectroscopy, and
      redispersion experiment. By casting the dilute dispersion of functionalized
      MWCNTs onto a hydrophilic Si surface, discrete and individual nanotubes can be
      observed by AFM.

PMID- 17181231
TI  - Conversion of ZnO nanorod arrays into ZnO/ZnS nanocable and ZnS nanotube arrays
      via an in situ chemistry strategy.
AB  - Vertically aligned ZnO nanorods with uniform diameter and length have been
      synthesized on a zinc foil substrate with ammonium persulfate as oxidant via a
      facile, larger scale production and inexpensively synthesized method without any
      templates or additives. SEM and XRD studies indicate that ZnO nanorods are well
      oriented along the c-axis. The PL spectrum indicates that our as-synthesized ZnO
      nanorods with a stronger and wider green emission are promising candidates as
      electron nanoconductors in nano-optoelectronic devices. Furthermore, by an
      effective thioglycolic acid-assisted solution route, well-aligned ZnO/ZnS
      nanocable and ZnS nanotube arrays have been successfully synthesized. ZnS
      nanotubes show a perfect hexagonal and obvious tubular shape. Our present
      strategy shows mild growth conditions and good reproducibility.

PMID- 17181232
TI  - Hydrogen production from a combination of the water-gas shift and redox cycle
      process of methane partial oxidation via lattice oxygen over LaFeO3 perovskite
      catalyst.
AB  - A redox cycle process, in which CH4 and air are periodically brought into contact
      with a solid oxide packed in a fixed-bed reactor, combined with the water-gas
      shift (WGS) reaction, is proposed for hydrogen production. The sole oxidant for
      partial oxidation of methane (POM) is found to be lattice oxygen instead of
      gaseous oxygen. A perovskite-type LaFeO3 oxide was prepared by a sol-gel method
      and employed as an oxygen storage material in this process. The results indicate
      that, under appropriate reaction conditions, methane can be oxidized to CO and H2
      by the lattice oxygen of LaFeO3 perovskite oxide with a selectivity higher than
      95% and the consumed lattice oxygen can be replenished in a reoxidation procedure
      by a redox operation. It is suggested that the POM to H2/CO by using the lattice
      oxygen of the oxygen storage materials instead of gaseous oxygen should be
      possibly applicable. The LaFeO3 perovskite oxide maintained relatively high
      catalytic activity and structural stability, while the carbonaceous deposits,
      which come from the dissociation of CH4 in the pulse reaction, occurred due to
      the low migration rate of lattice oxygen from the bulk toward the surface. A new
      dissociation-oxidation mechanism for this POM without gaseous oxygen is proposed
      based on the transient responses of the products checked at different surface
      states via both pulse reaction and switch reaction over the LaFeO3 catalyst. In
      the absence of gaseous-phase oxygen, the rate-determining step of methane
      conversion is the migration rate of lattice oxygen, but the process can be
      carried out in optimized cycles. The product distribution for POM over LaFeO3
      catalyst in the absence of gaseous oxygen was determined by the concentration of
      surface oxygen, which is relevant with the migration rate of lattice oxygen from
      the bulk toward the surface. This process of hydrogen production via selective
      oxidation of methane by lattice oxygen is better in avoiding the deep oxidation
      (to CO2) and enhancing the selectivity. Therefore, this new route is superior to
      general POM in stability (resistance to carbonaceous deposition), safety
      (effectively avoiding accidental explosion), ease of operation and optimization,
      and low cost (making use of air not oxygen).

PMID- 17181233
TI  - A first-principles analysis of hydrogen interaction in Ti-doped NaAlH4 surfaces:
      structure and energetics.
AB  - First principles density functional theory studies have been carried out to
      investigate the hydrogen interactions in Ti-doped NaAlH4 (001) and (100)
      surfaces. In both surfaces, Ti was found to energetically favor the interstitial
      sites formed by three neighboring AlH4- units and interact directly with them.
      The resulting local structure corresponds to a formula of TiAl3Hx with x = 12
      before hydrogen desorption starts. The hydrogen desorption energies from many
      positions of TiAl3Hx are reduced considerably as compared with that from the
      corresponding clean, undoped NaAlH4 surfaces. The almost invariant local
      environment surrounding Ti during dehydrogenation makes the TiAl3Hx complex a
      precursor state for the formation of experimentally observed TiAl3. The
      importance of the complex has been explored by analyzing the structures and
      energetics accompanying hydrogen desorption from the complex and from the
      neighboring AlH4- units. The TiAl3Hx has extended effects beyond the locally
      reducing hydrogen desorption energy. It facilitates low-energy hydrogen
      desorption by either transferring hydrogen to the TiAl3Hx complex or reducing
      hydrogen desorption energy in the neighboring AlH4- by linking these AlH4- units
      with the complex structure. The possible mechanisms for forming octahedral AlH6(3
      ) were also identified in the vicinity of TiAl3Hx. Desorbing hydrogen atoms
      between Ti and Al atoms causes a symmetrical expansion of Ti-Al bonds and leads
      to the formation of octahedral AlH6(3-).

PMID- 17181234
TI  - Novel Zn1-xMnxSe (x = 0.1-0.4) one-dimensional nanostructures: nanowires,
      zigzagged nanobelts, and toothed nanosaws.
AB  - Novel Zn1-xMnxSe one-dimensional nanostructures-straight nanowires (x = 0.1 and
      0.3), zigzagged nanobelts (x = 0.4), and toothed nanosaws (x = 0.4)-were
      synthesized using the chemical vapor deposition method. They all consisted of
      single-crystalline wurtzite ZnSe crystals, irrespective of the Mn content. In
      particular, the nanosaws have a unique structure in which double-sided teeth are
      rooted in the nanowire core and bent so as to align as two parallel rows. The
      long axis is parallel to the [010] direction, and all of the teeth have the
      [0001] growth direction. The X-ray diffraction pattern confirms the formation of
      wurtzite ZnSe crystal and the decrease of the lattice constant owing to Mn
      doping. The Mn2+ emission at 2.1 eV (appeared below 100 K), originating from the
      d-d (4T1 --> 6A1) transition, proves the effective substitution of Mn2+ ions at
      the tetrahedral coordinate sites.

PMID- 17181235
TI  - Equilibrium distributions of dipalmitoyl phosphatidylcholine and dilauroyl
      phosphatidylcholine in a mixed lipid bilayer: atomistic semigrand canonical
      ensemble simulations.
AB  - Conventional molecular dynamics (MD) simulations are seriously limited by the
      slow rate of diffusive mixing in their ability to predict lateral distributions
      of different lipid types within mixed-lipid bilayers using atomistic models. A
      method to overcome this limitation, using configuration-bias Monte Carlo (MC)
      "mutation" moves to transform lipids from one type to another in dynamic
      equilibrium, is demonstrated in binary fluid-phase mixtures of lipids whose tails
      differ in length by four carbons. The hybrid MC-MD method operates within a
      semigrand canonical ensemble, so that an equilibrium composition of the mixture
      is determined by a constant difference in chemical potential (Delta(mu)) chosen
      for the components. Within several nanoseconds, bilayer structures initiated as
      pure dipalmitoyl phosphatidylcholine (DPPC) or pure dilauroyl phosphatidylcholine
      (DLPC) converge to a common composition and structure in independent simulations
      conducted at the same Delta(mu). Trends in bilayer thickness, area per lipid,
      density distributions across the bilayer, and order parameters have been
      investigated at three mixture compositions and compared with results from the
      pure bilayers at 323 K. The mixtures showed a moderate increase in DPPC acyl tail
      sites crossing the bilayer midplane relative to pure DPPC. Correlations between
      lateral positions of the two lipid types within or across the bilayer were found
      to be weak or absent. While the lateral distribution is consistent with nearly
      ideal mixing, the dependence of composition on Delta(mu) indicates a positive
      excess free energy of mixing.

PMID- 17181236
TI  - Aqueous block copolymer-surfactant mixtures and their ability in solubilizing
      chlorinated organic compounds. A thermodynamic and SANS study.
AB  - Within the topic of surfactant enhanced solubilization of additives sparingly
      soluble in water, volumetric, solubility, conductivity, and small-angle neutron
      scattering (SANS) experiments on mixtures composed of alpha,omega-dichloroalkane,
      surfactant, copolymer, and water were carried out at 298 K. The triblock
      copolymers (ethylene oxide)132(propylene oxide)50(ethylene oxide)132 (F108) and
      (ethylene oxide)76(propylene oxide)29(ethylene oxide)76 (F68) were chosen to
      investigate the role of the molecular weight keeping constant the
      hydrophilic/hydrophobic ratio. The selected surfactants are sodium decanoate
      (NaDec) and decyltrimethylammonium bromide (DeTAB) with comparable hydrophobicity
      and different charged heads. The alpha,omega-dichloroalkanes were chosen as
      contaminant prototypes. For the water + surfactant + copolymer mixtures, both the
      volume and the SANS results straightforwardly evidenced that (1) monomers of
      NaDec and copolymer unimers generate small mixed aggregates, (2) monomers of
      DeTAB combined with copolymer unimers do not form aggregates, and (3) unimeric
      copolymer is solubilized into NaDec and DeTAB micelles. The alpha,omeaga
      dichloroalkanes presence induces the F108 aggregation even at very low copolymer
      composition. The addition of surfactant disintegrates the F108 aggregates and,
      consequently, the additive is expelled into the aqueous phase. Once F108 is in
      the unimeric state, it forms copolymer-micelle aggregates which incorporate the
      oil. In the case of F68 both the volumetric and the SANS data reveal that the
      additive does not alter the copolymer unimeric state. Moreover, they show that
      for the aqueous DeTAB-F68 system the additive trapping in both the copolymer
      micelle aggregate and the pure micelles takes place being enhanced in the former
      aggregate in agreement with solubility experiments. For the NaDec-F68 mixtures,
      an additional solubilization process in the premicellar copolymer-surfactant
      microstructures occurs. SANS and conductivity data show that the additive
      incorporation into the mixed and the pure micelles does not essentially influence
      the structural properties of the aggregates.

PMID- 17181237
TI  - Host matrix dependent fluorescence intensity modulation by an electric field in
      single conjugated polymer chains.
AB  - An electric field oscillating at a frequency approximately 1 Hz is found to
      induce strong modulation of the fluorescence intensity of single poly[2-methoxy,5
      (2'-ethyl-hexyloxy)-p-phenylene vinylene] (MEH-PPV) molecules (MW approximately
      10(6)) embedded in a poly(methyl methacrylate) (PMMA) matrix. The MEH-PPV polymer
      chains are carefully isolated from the electrodes to avoid effects of injection.
      In a polystyrene matrix, fluorescence intensity modulations are on average much
      less pronounced. The difference in average modulation depth can be explained in
      terms of lower field-induced exciton dissociation rates in the MEH
      PPV/polystyrene system compared to MEH-PPV/PMMA because of a lack of suitable
      acceptor sites. The observed electric field dependence of single-molecule
      fluorescence strongly suggests that energy transfer from singlet or even triplet
      excitons to long-living on-chain hole polarons contributes to the observed
      modulations. The observed large qualitative differences between the responses of
      different molecules probably reflect differences in chain topology and strongly
      anisotropic distributions of acceptor sites, while the hysteretic response of
      some molecules indicates conformational switching.

PMID- 17181238
TI  - Dispersion stability of colloids in sub- and supercritical water.
AB  - Dispersion stability of colloids has been investigated in sub- and supercritical
      water by measuring the hydrodynamic diffusion coefficients of the particles by
      means of dynamic light scattering. It is interestingly found that coagulation of
      the colloids in sub- and supercritical water is a universal phenomenon
      irrespective of the material of the colloids. Highly charged colloids were found
      to be more stable in water against high temperature. Numerical analysis reveals
      that the stability of the colloids at elevated temperature and pressure is
      primarily governed by the temperature dependence of the dielectric constant of
      the medium. The effect of the temperature dependence of the ion product of water
      (pKw) was found to be very little. Surface charge density and Stern potential may
      change with respect to temperature due to the readjustment of the ion
      concentration in the diffuse layer through the enhanced ion product and reduced
      dielectric constant of water. These are the secondary causes of the particle
      coagulations in sub- and supercritical water.

PMID- 17181239
TI  - Engineered complex emulsion system: toward modulating the pore length and
      morphological architecture of mesoporous silicas.
AB  - In the complex alkane/P123/TEOS/H2O emulsion system, an emulsion engineering
      method to modulate pore length and morphological architecture of mesoporous
      materials has been built. With fine tuning of the synthetic parameters (e.g., the
      composition of the synthetic mixtures, temperature, stirring, etc.), a series of
      chemically significant mesostructures (i.e., short-pore SBA-15 materials) with
      tunable pore length and morphological architecture have been successfully
      constructed. The effects of alkane solubilizates on pore length and particle
      morphology are discussed. The resulting short-pore materials would have potential
      applications in the fields of adsorption/separation of biomolecules and inclusion
      chemistry of guest species, etc.

PMID- 17181240
TI  - Characterization of Pt nanoparticles deposited onto carbon nanotubes grown on
      carbon paper and evaluation of this electrode for the reduction of oxygen.
AB  - Multiwalled carbon nanotubes (MWCNTs) were grown on the fibers of a commercial
      porous carbon paper used as carbon-collecting electrodes in fuel cells. The tubes
      were then covered with Pt nanoparticles in order to test these gas diffusion
      electrodes (GDEs) for oxygen reduction in H2SO4 solution and in H2/O2 fuel cells.
      The Pt nanoparticles were characterized by cyclic voltammetry, transmission
      electron microscopy, and X-ray photoelectron spectroscopy. The majority of the Pt
      particles are 3 nm in size with a mean size of 4.1 nm. They have an
      electrochemically active surface area of 60 m2/g Pt for Pt loadings of 0.1-0.45
      mg Pt/cm2. Although the electroactive Pt surface area is larger for commercial
      electrodes of similar loadings, Pt/MWCNT electrodes largely outperform the
      commercial electrode for the oxygen reduction reaction in GDE experiments using
      H2SO4 at pH 1. On the other hand, when the same electrodes are used as the
      cathode in a H2/O2 fuel cell, they perform only slightly better than the
      commercial electrodes in the potential range going from approximately 0.9 to
      approximately 0.7 V and have a lower performance at lower voltages.

PMID- 17181241
TI  - MP2 study on adsorption of hydrated Na+ and Au+ cations on the Au(111) surface.
AB  - The interactions of Na+ and Au+ cations with an Au(111) surface in the presence
      and absence of water molecules were investigated using Au18 and Au22 cluster
      models and the MP2 method with a triple-zeta valence basis set. The interactions
      between Na+ ions and the Au(111) surface were found to be primarily
      electrostatic, contrary to the much stronger Au+-Au(111) interactions that were
      dominated by orbital contributions. The largest CP-corrected MP2 adsorption
      energies were -156.9 kJ/mol for Na+ and -478.7 kJ/mol for Au+. When hydrated, Na+
      prefers to be completely surrounded by water molecules rather than adsorbed to
      the surface, whereas Au+ remains adsorbed to the surface as water molecules bond
      with each other and with the Au surface. CP correction did not change the
      relative adsorption energy trends of Na+ or Au+ ions, but it had an effect on the
      interaction energy trends of the hydrated cations because of the weak water
      surface and water-water interactions.

PMID- 17181242
TI  - Self-assembled monolayers on mercury probed in a modified surface force
      apparatus.
AB  - Self-assembled monolayers (SAMs) of three thiol compounds formed on mercury are
      investigated by a combination of cyclic voltammetry, electrocapillary curves, and
      a novel method of measuring electrical double-layer properties. The last method
      involves a modified surface force apparatus in which a flat mica surface is
      pressed down toward a fixed mercury drop held beneath it, while both are immersed
      in aqueous electrolyte solution. Optical interference measurements are made of
      the mica-mercury separation as a function of electrical potential applied to the
      mercury, which yields information on the double-layer interaction between the two
      surfaces. Mercury is decorated by SAMs of 11-mercapto-1-undecanoic acid, which is
      shown to bring negative charge to the mercury/aqueous interface due to
      dissociation of the carboxylic acid groups; 11-mercapto-1-undecanol, which
      although it is uncharged changes the dipole potential of the interface; and 1
      undecanethiol, which likewise changes the dipole potential, but by a different
      amount. The difference between the changes in dipole potential (90 mV) can be
      related to the different terminal groups of these two SAMs, -CH3 compared to -OH,
      that are in contact with the aqueous phase.

PMID- 17181243
TI  - First principles density functional study of the adsorption and dissociation of
      carbonyl compounds on magnesium oxide nanosurfaces.
AB  - The adsorption and dissociation of three carbonyl compounds, formaldehyde,
      acetaldehyde, and acetone, on the magnesium oxide nanosurface, consisting of four
      stacked (MgO)3 hexagons, is investigated by first principles density functional
      theory (DFT). In the case of formaldehyde, strongly chemisorbed species, with
      carboxylate-like structures, are initially formed. These may subsequently undergo
      heterolytic cleavage of an aldehyde C-H bond to form formate ions involving a
      surface oxide ion and a hydride ion adsorbed over the magnesium dication
      [(MgH+)(HCOO-)]. For acetaldehyde, besides this reaction leading to the formation
      of acetate, the methyl hydrogen of the adsorbed species also tends to attach
      itself to a surface oxide ion, yielding surface hydroxyl ions and adsorbed
      [CH2=C(H)OMg]+. These results are in accord with our previous experimental and
      theoretical results. In particular, the shift of the aldehyde C-H vibration band
      to higher frequency and the appearance of OH bands in the infrared spectrum are
      clearly accounted for. For acetone, the mechanism is found to be similar, i.e., a
      methyl hydrogen shift to yield surface enolate. Again, this is in agreement with
      experimental studies.

PMID- 17181244
TI  - Structures and reaction mechanisms of propene oxide isomerization on H-ZSM-5: an
      ONIOM study.
AB  - The isomerization mechanisms of propene oxide over H-ZSM-5 zeolite have been
      investigated via the utilization of 5T and 46T cluster models calculated by the
      B3LYP/6-31G(d,p) and the ONIOM(B3LYP/6-31G(d,p):UFF) methods, respectively. The
      reactions are considered to proceed through a stepwise mechanism: (1) the epoxide
      ring protonation, and concurrently the ring-opening, and (2) the 1,2-hydride
      shift forming the adsorbed carbonyl compound. Because of the asymmetric structure
      of propene oxide, two different C-O bonds (more or less substituted carbon atom
      sides) can be broken leading to two different types of products, propanal and
      propanone. The ring-opening step of these mechanisms is found to be the rate
      determining step with an activation barrier of 38.5 kcal/mol for the propanal and
      of 42.4 kcal/mol for the propanone. Therefore, the propanal is predicted to be
      the main product for this reaction.

PMID- 17181245
TI  - Photophysical properties of hydroxylated amphiphilic poly(p-phenylene)s.
AB  - A homologous series of polyhydroxylated poly(p-phenylene)s with different alkoxy
      groups (C6PPPOH, C12PPPOH, and C18PPPOH) were synthesized with use of the Suzuki
      polycondensation reaction. Comparative studies of the structure correlation
      between their photophysical properties and film morphology is described. The
      absorption and emission spectra of polymers in solution and thin films showed
      similar features indicating that the electronic properties in solution were
      retained in the film state. Compared to the polymer with the short alkoxy chains
      (C6PPPOH), the polymers with long alkoxy groups (C12PPPOH and C18PPPOH) showed
      improved film forming properties with continuous and smooth film morphology. The
      absorption properties of the C12PPPOH showed an enhanced effective conjugation
      length and high quantum yield implying planarization of the backbone through
      alkoxy chain packing (C12H25O-) and potential hydrogen bonds. No overlap in the
      absorption and emission spectra was observed, which indicated minimized excimer
      formation or excitation energy transfer in the films. Time-resolved fluorescence
      measurements showed that the decay times increased from 43 ps (C6PPPOH) to 78 ps
      (C12PPPOH) and 99 ps (C18PPPOH). Electrochemical studies were performed for all
      polymers and the observed oxidation potential for C6PPPOH was higher than that of
      C12PPPOH and C18PPPOH. In addition, the C12PPPOH has the lowest band gap of
      DeltaE = 2.59 eV when compared to the 3.1 (C6PPPOH) and 2.61 eV (C18PPPOH) gaps.
      The optical band gaps estimated from the absorption onset of the polymers are
      significantly higher than those obtained from electrochemical data. C12PPPOH was
      chosen for investigating the charge carrier mobility by the time-of-flight (TOF)
      technique. The observed results also showed negative field dependent values of
      the drift mobility for the polymer C12PPPOH.

PMID- 17181246
TI  - Preparation, crystal structure, and thermal stability of the cadmium sulfide
      nanoclusters Cd6S44+ and Cd2Na2S4+in the sodalite cavities of zeolite A (LTA).
AB  - The crystal structure and thermal stability of two cadmium sulfide nanoclusters
      prepared in zeolite A (LTA) have been studied by XPS, TGA, and single-crystal and
      powder XRD. The crystal structures of Cd2.4Na3.2(Cd6S4)0.4(Cd2Na2S)0.6(H2O)> or
      =5.8[Si12Al12O48]-LTA (a = 12.2919(7) A, crystal 1 (hydrated)) and
      /Cd4Na2(Cd2O)(Na2O)/[Si12Al12O48]-LTA (a = 12.2617(4) A, crystal 2 (dehydrated))
      were determined by single-crystal methods in the cubic space group Pm3m at 294(1)
      K. Crystal 1 was prepared by ion exchange of Na12-LTA in an aqueous stream 0.05 M
      in Cd2+, followed by washing in a stream of water, followed by reaction in an
      aqueous stream 0.05 M in Na2S. Crystal 2 was made by dehydrating crystal 1 at 623
      K and 1 x 10(-6) Torr for 3 days. In crystal 1, Cd6S4(4+) nanoclusters were found
      in and extending out of about 40% of the sodalite cavities. Central to each
      Cd6S4(4+) cluster is a Cd4S4 unit (interpenetrating Cd2+ and S2- tetrahedra with
      near Td symmetry, Cd-S = 2.997(24) A, Cd-S-Cd = 113.8(12) degrees, and S-Cd-S =
      58.1(24) degrees). Each of the two remaining Cd2+ ions bonds radially through a 6
      ring of the zeolite framework to a sulfide ion of this Cd4S4 unit (Cd-S = 2.90(8)
      A). In each of the remaining 60% of the sodalite cavities of crystal 1, a planar
      Cd2Na2S4+ cluster was found (Cd-S/Na-S = 2.35(5)/2.56(14) A and Cd-S-Cd/Na-S-Na =
      122(5)/92(7) degrees). Cd6S4(4+) and Cd2Na2S4+ are stable within the zeolite up
      to about 700 K in air. Upon vacuum dehydration at 623 K, all sulfur was lost
      (crystal 2). Instead as anions, only two oxide ions remain per sodalite unit. One
      bridges between two Cd2+ ions (Cd2O2+, Cd-O = 2.28(3) A) and the other between
      two Na+ ions (Na2O, Na-O = 2.21(10) A).

PMID- 17181247
TI  - Cleaning and hydrophilization of atomic force microscopy silicon probes.
AB  - The silicon surface of commercial atomic force microscopy (AFM) probes loses its
      hydrophilicity by adsorption of airborne and package-released hydrophobic organic
      contaminants. Cleaning of the probes by acid piranha solution or discharge plasma
      removes the contaminants and renders very hydrophilic probe surfaces. Time-of
      flight secondary-ion mass spectroscopy and X-ray photoelectron spectroscopy
      investigations showed that the native silicon oxide films on the AFM probe
      surfaces are completely covered by organic contaminants for the as-received AFM
      probes, while the cleaning methods effectively remove much of the hydrocarbons
      and silicon oils to reveal the underlying oxidized silicon of the probes.
      Cleaning procedures drastically affect the results of adhesive force measurements
      in water and air. Thus, cleaning of silicon surfaces of the AFM probe and sample
      cancelled the adhesive force in deionized water. The significant adhesive force
      values observed before cleaning can be attributed to formation of a bridge of
      hydrophobic material at the AFM tip-sample contact in water. On the other hand,
      cleaning of the AFM tip and sample surfaces results in a significant increase of
      the adhesive force in air. The presence of water soluble contaminants at the tip
      sample contact lowers the capillary pressure in the water bridge formed by
      capillary condensation at the AFM tip-sample contact, and this consequently
      lowers the adhesive force.

PMID- 17181248
TI  - Phase transitions of capillary-held liquids in a slit-like pore.
AB  - Dynamics of capillary held liquids plays important roles in a wide range of
      systems including adhesion, printing of paints and inks, the behavior of wet
      granular materials, and the mass transfer through porous media. Recent study
      suggested the presence of two distinct modes for the disappearance of capillary
      held liquids in a slit-like pore of adjustable slit width that depended on the
      slit-opening rates. In contrast to the first mode that is well-documented in
      terms of the Young-Laplace equation, a novel and unexpected mode was observed
      when the liquid bridge was held in the vicinity of the thermodynamic phase
      boundary (equilibrium Kelvin length). Here we extended the study to three new
      compounds that have a wide range of vapor pressures. An evaporating liquid bridge
      developed large refractive index gradients that extended over a few micrometers
      from the edge of the meniscus once the slit width was increased beyond the
      equilibrium Kelvin length. This interfacial region with depleted refractive index
      retreated inward as the meniscus shrank with time, and the refractive index of
      the entire bridge subsequently fell from that of the liquid once the interfacial
      regions from the opposite sides of the shrinking bridge met at the center. The
      refractive index recovered to that of the liquid when the slit width was closed
      to below the Kelvin length and the vapor was allowed to recondense. The time
      scale of the evaporation and condensation depended on the size of the surface
      gap, and, when the surfaces were placed at a separation very close to the Kelvin
      length, it was possible to detect a stage in which the system was in an apparent
      kinetic equilibrium between two physical states--with and without the liquid
      connecting the two surfaces.

PMID- 17181249
TI  - Biocompatible lipid-based liquid crystals and emulsions.
AB  - Due to its potential relevance as a fully biocompatible formulation useful in
      cosmetic, food, and pharmaceutical applications, the glycerol trioleate/sodium
      oleate/water ternary system was investigated via optical microscopy and NMR
      methods. The ternary diagram is dominated by monophasic and biphasic regions
      where a lamellar phase coexists with different isotropic phases. A broad emulsion
      region, characterized by small oil droplets dispersed within the lamellar phase,
      extends from the center toward the water corner of the diagram. Information on
      the inner structure of these emulsion-like samples is supplied by modeling water
      and oil NMR self-diffusion data. Sizing of oil droplets was provided at different
      storage times. A highly polydisperse log-normal distribution was observed. The
      presence of the liquid crystalline phase is called into play for the negligible
      differences found in the droplets size distribution upon samples aging. Indeed,
      samples within this region stored at 25 degrees C did not show phase separation
      after several months from their preparation.

PMID- 17181250
TI  - "Nanocasting": using SBA-15 silicas as hard templates to obtain ultrasmall
      monodispersed gamma-Fe2O3 nanoparticles.
AB  - This work describes the use of mesoporous SBA-15 silicas as hard templates for
      the size-controlled synthesis of oxide nanoparticles, with the pores acting as
      nanoscale reactors. This fundamental work is mainly aimed at understanding
      unresolved issues concerning the occurrence and size dependence of phase
      transitions in oxide nanocrystals. Aqueous solutions of Fe(NO3)3*9H2O are
      deposited inside the pores of SBA-15 silicas with mesopore diameters of 4.3, 6.6,
      and 9.5 nm. By calcination, the nitrate salt transforms into FeOx oxides. The XRD
      peaks of nanocrystals are broad and overlapping, resulting in ambiguities
      attributed to a given allotropic variety of Fe2O3 (alpha, epsilon, or gamma) or
      Fe3O4. The association of XRD, SAED, and Raman information is necessary to solve
      these ambiguities. The metastable gamma-Fe2O3 variety is selectively formed at
      low Fe/Si atomic ratio (ca. 0.20) and when a low calcination temperature is used
      (773 or 873 K followed by quenching to room temperature once the targeted
      temperature is reached). The small size dispersion of the patterned
      nanoparticles, suggested on a local scale by TEM, is confirmed statistically by
      magnetic measurements. The nanoparticles have a superparamagnetic behavior around
      room temperature. Their magnetic moments (from 220 to 370 mB), their sizes (from
      4.0 to 4.8 nm), and their blocking temperatures (from 36 to 58 K) increase with
      the silica template mesopore diameter. Their magnetic properties are compared to
      those of standard gamma-Fe2O3 nanoparticles of similar size, obtained by
      coprecipitation in water and stabilized by a citrate coating.

PMID- 17181251
TI  - Oxidative decomposition of rhodamine B dye in the presence of VO2+ and/or Pt(IV)
      under visible light irradiation: N-deethylation, chromophore cleavage, and
      mineralization.
AB  - In order to make clear the roles of dissolved O2 in the photocatalytic
      decomposition of organic pollutants and to discriminate different degradation
      pathways (N-deethylation, chromophore cleavage, and mineralization) during the
      degradation of dye, the photodegradation of rhodamine B (RhB) has been
      investigated using vanadate and/or platinum species as electron acceptors in the
      presence or absence of O2 under visible light irradiation. It was found that with
      VO2+ as electron acceptor, RhB underwent efficient N-deethylation under visible
      light irradiation and O2 was found to slow down this process significantly.
      Little mineralization has been observed in the presence and absence of O2 in VO2+
      systems. By contrast, Pt(IV) resulted in the cleavage of conjugated chromophore
      structure (bleaching) of RhB dye under the otherwise identical conditions. In
      this case, the presence of O2 did not affect the bleaching rate of the dye, but
      enhanced greatly the mineralization. Both cleavage of conjugated chromophore
      structure and N-deethylation occurred simultaneously upon the coaction of VO2+
      and Pt(IV) under visible light irradiation. The mineralization yield of the
      combined system was evidently higher than the expected summation of separate
      ones. TOC, XPS, and ESR results indicate that in the VO2+ and Pt(IV) combined
      system VO2+ not only oxidized RhB leading to deethylation but also oxidized the
      reduced Pt(II) to regenerate Pt(IV) leading to the further cleavage of
      chromophore structure of RhB, which behaved quite different from the separate
      ones. A mechanism was also proposed to interpret the different pathways for the
      oxidative photodecomposition of RhB under visible irradiation.

PMID- 17181252
TI  - In situ FT-IR studies on the mechanism of selective catalytic reduction of NOx by
      propene over SnO2/Al2O3 catalyst.
AB  - The mechanism of the selective catalytic reduction (SCR) of NOx by propene over
      SnO2/Al2O3 catalyst in the presence of oxygen has been investigated using in situ
      Fourier transform infrared (FT-IR) spectroscopy. In situ IR measurements indicate
      that acetate and formate, which are the derivatives of the partial oxidation of
      propene, play a crucial role in the formation of NCO by reacting with the
      reactive monodentate nitrate species. The resulting NCO species subsequently
      reacts with NOx to form N2. The presence of oxygen substantially contributes to
      the partial oxidation of propene and thus shows a promoting effect for the NOx
      reduction.

PMID- 17181253
TI  - SOx storage materials under Lean-Rich cycling conditions--Part II: influence of
      Pt, H2O, and cycling time.
AB  - The role of Pt and the influence of the reaction conditions during lean-rich
      cycling experiments were studied on a second generation SOx trapping material.
      The combination of the Generalized 2-D Correlation Analysis, 2-D Sample-Sample
      Correlation Analysis, and Factor Analysis using the MCR-ALS technique was applied
      to identify the reactive species. Transient surface sulfate species were formed
      under oxidative reaction conditions (lean mode) and decomposed under reducing
      reaction conditions (rich operation mode). The reduction of this species was
      identified to be the main contribution to the SO2 release observed under dynamic
      flow conditions. Pt facilitates the formation of sulfates but also catalyzes the
      reduction of the transient surface sulfate species leading to a higher amount of
      SO2 released under rich conditions. In the presence of water, this effect was
      diminished, which was found to be mainly a result of the suppressed formation of
      surface sulfate species caused by the faster transport of SO2 into the bulk phase
      of the SOx trapping component (BaCO3). Increasing the time under reducing
      conditions in the cycles leads to an enhanced reduction of the surface during
      rich conditions. The presence of water did not influence the bulk type species.
      It is proposed that for effective SO2 storage materials, strong SOx adsorption
      sites on the surface, the presence of water, and a short time under reducing
      conditions are essential.

PMID- 17181254
TI  - Adsorption of glucose oxidase onto plasma-polymerized film characterized by
      atomic force microscopy, quartz crystal microbalance, and electrochemical
      measurement.
AB  - Adsorption of glucose oxidase (GOD) onto plasma-polymerized thin films (PPF) with
      nanoscale thickness was characterized by atomic force microscopy (AFM), quartz
      crystal microbalance (QCM), and electrochemical measurements. The PPF surface is
      very flat (less than 1-nm roughness), and its properties (charge and wettability)
      can be easily changed while retaining the backbone structure. We focused on three
      types of surfaces: (1) the pristine surface of hexamethyldisiloxane (HMDS) PPF
      (hydrophobic and neutral surface), (2) an HMDS PPF surface with nitrogen-plasma
      treatment (hydrophilic and positive-charged surface), and (3) an HMDS PPF surface
      treated with oxygen plasma (hydrophilic and negative-charged surface). The AFM
      image showed that the GOD molecules were densely adsorbed onto surface 2 and that
      individual GOD molecules could be observed. The longer axis of GOD ellipsoid
      molecules were aligned parallel to the surface, called the "lying position",
      because of electrostatic association. On surface 1, clusters of GOD molecules did
      not completely cover the original PPF surface (surface coverage was ca. 60%). The
      10-nm-size step height between the GOD clusters and the PPF surface suggests that
      the longer axes of individual GOD molecules were aligned perpendicular to the
      surface, called the "standing position". On surface 3, only a few of the GOD
      molecules were adsorbed because of electrostatic repulsion. These results
      indicate that the plasma polymerization process can facilitate enhancement or
      reduction of protein adsorption. The AFM images show a corresponding tendency
      with the QCM profiles. The QCM data indicate that the adsorption behavior obeys
      the Langmuir isotherm equation. The amperometric biosensor characteristics of the
      GOD-adsorbed PPF on a platinum electrode showed an increment in the current
      because of enzymatic reaction with glucose addition, indicating that enzyme
      activity was mostly retained in spite of irreversible adsorption.

PMID- 17181255
TI  - A microfluidic channel flow cell for electrochemical ESR.
AB  - The design, fabrication, and characterization of microfluidic channel flow
      devices for in situ simultaneous hydrodynamic electrochemical ESR is reported.
      The microelectrochemical reactors consist of gold film electrodes situated within
      rectangular ducts of height 350 microm and widths in the range 500-2000 microm.
      The small dimensions of the channels result in minimal dielectric loss when
      centralized within a cylindrical TE011 resonant cavity, leading to a high level
      of sensitivity. This is demonstrated by using the one-electron oxidation of
      N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) in acetonitrile as a model
      system, wherein the ESR spectra obtained for the corresponding stable radical
      cation are of a high signal-to-noise ratio. Signal intensity is measured as a
      function of flow rate for this system, and the behavior is validated by means of
      3-dimensional numerical modeling of the hydrodynamic flow profile.

PMID- 17181256
TI  - Effect of pre-covered oxygen on the dehydrogenation reactions over copper
      surface: a density functional theory study.
AB  - Dehydrogenation of five species including CH3OH, CH3O, H2COO, NH3, and H2O over
      clean and oxygen-modified copper surfaces has been investigated by the first
      principle density functional calculations within the generalized gradient
      approximation. The reaction enthalpies and the activation energies have been
      calculated for 10 elementary steps corresponding to the direct and oxygen
      assisted cleavage of X-H bonds (X = O, N, C). The DFT-GGA results showed that the
      pre-adsorbed oxygen always facilitates the dehydrogenation reaction by decreasing
      the reaction enthalpies and the activation energies. The obtained results are in
      general agreement with experimental observations.

PMID- 17181257
TI  - Electrooxidation of methanol on upd-Ru and upd-Sn modified Pt electrodes.
AB  - The electrochemical oxidation of methanol has been investigated on
      underpotentially deposited-ruthenium-modified platinum electrode (upd-Ru/Pt) and
      on underpotentially deposited-tin-modified platinum electrode (upd-Sn/Pt). The
      submonolayers of upd-Ru and upd-Sn on a Pt electrode increased the rate of
      methanol electrooxidation several times as large as that on a pure Pt electrode.
      The best performance for methanol electrooxidation was obtained on a ternary
      platinum based catalyst modified by upd-Ru and upd-Sn simultaneously. The
      influence of the submonolayers of upd-Ru adatoms and upd-Sn adatoms on the
      oxidation of methanol in acid has been investigated. The effect of Ru on methanol
      electrooxidation lies on the distribution of Ru adatoms on a Pt surface. It has
      been shown that as long as the amount of upd-Ru deposits were controlled in a
      proper range, upd-Ru deposits would enhance the methanol oxidation obtained on a
      Pt electrode at whichever deposition potential the upd-Ru deposits were obtained.
      The effects of tin are sensible to the potential range. The enhancement effect of
      upd-Sn adatoms for the oxidation of methanol will disappear as the electrode
      potential is beyond a certain value. It is speculated that there exists a
      synergetic effect on the Pt electrode as adatoms Ru and Sn participate
      simultaneously in the methanol oxidation.

PMID- 17181258
TI  - Effect of branched conjugation structure on the optical, electrochemical, hole
      mobility, and photovoltaic properties of polythiophenes.
AB  - Four branched polythiophenes (PTs) with different ratios of conjugated
      terthiophene-vinylene side chains, PT-TThV10 to PT-TThV40, were synthesized by
      Stille coupling reaction. The polymers exhibited reversible p-doping/dedoping
      (oxidation/re-reduction) and n-doping/dedoping (reduction/reoxidation) processes.
      The absorption spectra, hole mobility, and photovoltaic properties of the
      polymers were much improved in comparison with the PT derivative without the
      terthiophene-vinylene side chain and were influenced by the content of the
      conjugated side chains. With the increase of the content of the conjugated side
      chains, the absorption peak of the branched PTs enhanced and blue-shifted. The
      maximum hole mobility reached 6.35 x 10(-4) cm2/V.s (SCLC method) and the maximum
      power conversion efficiency of the polymer solar cell reached 1.91% under the
      illumination of AM 1.5, 100 mW/cm2, for the polymer with 20% terthiophene
      vinylene side chains. The results indicate that the branched PTs with suitable
      content of the terthiophene-vinylene side chains could be promising photovoltaic
      materials.

PMID- 17181259
TI  - Quenching of photoluminescence in conjugates of quantum dots and single-walled
      carbon nanotube.
AB  - Development of quantum dot (QD) based device components requires controlled
      integration of QDs into different photonic and electronic materials. In this
      regard, introduction of methods for regular arrangement of QDs and investigation
      of properties of QD-based assemblies are important. In the current work we report
      (1) controlled conjugation of CdSe-ZnS QDs to sidewall-functionalized single
      walled carbon nanotube (SWCNT) templates (2) and the effect of conjugation of QDs
      to SWCNT on the photoluminescence (PL) properties of QDs. We identified that PL
      intensity and lifetime of QDs are considerably reduced after conjugation to
      SWCNT. The origin of the quenching of the PL intensity and lifetime was discussed
      in terms of Forster resonance energy transfer (FRET). FRET involves nonradiative
      transfer of energy from a photoexcited QD (energy donor) to a nearby SWCNT
      (energy acceptor) in the ground state. This was examined by varying the density
      of QDs on SWCNT and conjugating smaller and bigger QDs to the same SWCNT. We
      estimated the FRET efficiency in QD-SWCNT conjugates from the quenching of the PL
      intensity and lifetime and identified that FRET is independent of the density and
      type of QDs on SWCNT but inherent to QD-SWCNT conjugates.

PMID- 17181260
TI  - Tuning the hole injection barrier at the organic/metal interface with self
      assembled functionalized aromatic thiols.
AB  - Self-assembled functionalized aromatic thiols (oligophenylenes composed of
      building blocks of dimethoxy-substituted phenylenes, perfluoro-substituted
      phenylenes, and a terminal thiol group) were used to tune the hole injection
      barrier (Delta(h)) of copper(II) phthalocyanine (CuPc) on Au(111). Synchrotron
      based high-resolution photoemission spectroscopy study reveals a significant
      reduction of Delta(h) by as much as 0.75 eV from Delta(h) = 0.9 eV for
      CuPc/Au(111) to Delta(h) = 0.15 eV for CuPc/BOF/Au(111), where BOF represents 4
      pentafluorophenyl-1-(p-thiophenyl)-2,5-dimethoxybenzene. The delocalized pi
      orbitals of these functionalized aromatic thiols greatly facilitate effective
      charge transfer (hole or electron) across the SAM interface as compared to
      alkanethiols, hence making this novel interface modification scheme a simple and
      effective way to tune the hole injection barrier. This method has potential
      applications in molecular electronics, organic light-emitting diodes (OLED),
      organic field-effect transistors (OFETs), and organic solar cells.

PMID- 17181261
TI  - Infrared spectroscopy of competitive interactions between liquid crystals, metal
      salts, and dimethyl methylphosphonate at surfaces.
AB  - We report the use of Fourier transform polarization modulation infrared
      reflection-absorption spectroscopy (PM-IRRAS) to characterize the influence of
      dimethyl methylphosphonate (DMMP) on the molecular interactions occurring within
      thin films of nitrile-containing liquid crystals supported on surfaces presenting
      metal perchlorate salts. Infrared spectra obtained using thin films of 4'-octyl-4
      biphenylcarbonitrile (8CB) supported on copper(II) perchlorate salts reveal the
      nitrile groups of 8CB to be coordinated to the copper(II) on these surfaces, and
      subsequent exposure of the system to DMMP to result in the elimination of these
      coordinated nitrile groups. Concurrently, evidence of coordination of the
      phosphoryl group of DMMP with copper(II) is provided by measurement of a shift of
      the phosphoryl stretch from 1246 to 1198 cm(-1). In contrast, surfaces presenting
      nickel(II) perchlorate salts only weakly coordinate with DMMP [the phosphoryl
      peak shifts from 1246 to 1213 cm(-1) in the presence of nickel(II)], and exposure
      of 8CB to DMMP results in only partial loss of coordination of the nitrile groups
      of 8CB with nickel(II). These PM-IRRAS measurements and others reported in this
      article provide insights into the molecular origins of macroscopic ordering
      transitions that are observed when micrometer-thick films of nitrile-containing
      liquid crystals supported on copper(II) or nickel(II) perchlorate are exposed to
      DMMP: Upon exposure to DMMP, nematic phases of 4'-pentyl-4-biphenylcarbonitrile
      (5CB) supported on copper(II) perchlorate salts undergo ordering transitions,
      whereas 5CB supported on nickel(II) perchlorate salts do not. Our IR results
      support the hypothesis that these ordering transitions reflect the relative
      strengths of coordination interactions occurring between the 5CB, DMMP, and the
      metal salts at these interfaces.

PMID- 17181262
TI  - Detection and spectral analysis of trifluoromethyl groups at a surface by sum
      frequency generation vibrational spectroscopy.
AB  - Sum frequency generation (SFG) vibrational spectroscopy was used to detect the
      presence of trifluoromethyl groups on the surface of 4-(trifluoromethyl)benzyl
      alcohol (TFMBA) in air. Supplementary data from infrared and Raman spectra were
      correlated to ab initio calculations by use of density functional theory (DFT)
      for TFMBA and three related compounds to reliably assign vibrational modes to the
      spectra. It was shown that strongly ordered CF3 groups dominate the surface of
      the TFMBA, and the vibrational modes of this functional group are strongly
      coupled to the benzene ring of the benzyl alcohol. This coupling, along with the
      SFG activity of the CF3 group, is removed with the insertion of an oxygen atom
      between the CF3 group and the benzene ring.

PMID- 17181263
TI  - Dynamic instabilities and mechanism of the electrochemical oxidation of
      thiosulfate.
AB  - The electrochemical oxidation of thiosulfate is revealed to have two distinct
      oscillatory regimes in both linear potential and galvanic voltammograms, where
      various nonlinear behaviors such as period-2, mixed-mode and quasi-periodic
      oscillations, and chaos are observed under potentiostatic or galvanostatic
      conditions. Electrochemical impedance spectroscopy and iR compensation
      characterization indicate that, depending on the operating conditions, the system
      could be either a strictly potentiostatic oscillator or an S-shaped negative
      differential resistance oscillator. Chronoamperometry measurements reveal that
      the first oscillatory process involves a single-electron transfer, whereas within
      the second oscillatory regime the average number of electrons transferred is
      around 3.8. Measurements with capillary electrophoresis and chemical methods
      illustrate that the oxidation products include S2O6(2-), S4O6(2-), S5O6(2-),
      S3O6(2-), and SO4(2-).

PMID- 17181264
TI  - Multiple Coordination of CO on Molybdenum Nanoparticles: Evidence for
      Intermediate Mox(CO)y Species by XPS and UPS.
AB  - CO chemisorption on the metallic molybdenum nanoparticles supported on the thin
      alumina film was investigated by X-ray photoelectron spectroscopy (XPS) and
      ultraviolet photoelectron spectroscopy (UPS). A binary compound of molybdenum and
      CO is found to be formed on the surface upon CO dose, accompanied with a positive
      binding energy shift of the Mo 3d doublet and a localized Mo 4d valence band. A
      loose packing of the metallic molybdenum favors the formation of this
      intermediate Mox(CO)y species. The formation of the Mox(CO)y species implies that
      the property of the metallic molybdenum nanoparticles on the thin alumina film is
      much different from that of the bulk molybdenum, indicating a significant
      nanometer size effect.

PMID- 17181265
TI  - Effect of aluminum on the nature of the iron species in Fe-SBA-15.
AB  - We report the preparation of highly ordered mesoporous Fe-Al-SBA-15 with isolated
      extraframework Fe species under acidic conditions. The materials were
      characterized by means of UV resonance Raman spectroscopy, in conjunction with
      BET, XRD, TEM, UV-vis, H2-TPR, FT-IR, and 27Al MAS NMR spectroscopy. The addition
      of both Fe and Al to the synthesis gel of SBA-15 results in the formation of
      isolated extraframework Fe species located close to the framework Al ions and the
      Fe content an order of magnitude higher than that in Fe-SBA-15 synthesized
      without Al. The existence of anchored extraframework Fe species was confirmed by
      the presence of a strong absorption band at 270 nm, hydrogen reduction at
      relatively low temperature, and the presence of a resonance Raman band at 1140
      cm(-1). The location of Fe in close proximity to framework Al nuclei is further
      supported by 27Al MAS NMR measurements. Two characteristic UV Raman bands at 510
      cm(-1) and 1090 cm(-1) excited by 244-nm laser are assigned to Fe-O-Si symmetric
      and asymmetric stretching modes of isolated tetrahedral Fe ions in the silica
      framework for Fe-SBA-15. The resonance Raman band at 1140 cm(-1) excited by 325
      nm laser is attributed to the asymmetric stretching mode of the isolated
      extraframework iron species in Fe-Al-SBA-15. The isolated Fe species close to
      framework Al species are stable in acidic HCl solution, whereas the majority of
      Fe species in Fe-SBA-15 can be easily removed.

PMID- 17181267
TI  - Specific heat of molecular crystals from atomic mean square displacements with
      the Einstein, Debye, and Nernst-Lindemann models.
AB  - Analysis of atomic displacement parameters (ADPs) from multitemperature
      diffraction data provides mean-field molecular translation and libration
      frequencies. These quantities have been combined with molecular deformation
      frequencies calculated ab initio, e.g. by DFT methods, to calculate the specific
      heat Cv of molecular crystals of naphthalene, anthracene, and
      hexamethylenetetramine. If the difference Cp - Cv is represented by the Nernst
      Lindemann relation, Cp curves from diffraction experiments and ab initio
      calculations agree well with those based on calorimetry. Agreement is better if
      the Debye rather than the Einstein model is chosen to represent the contribution
      of the translational vibrations. Compressibilities estimated from the differences
      Cp - Cv are 2-5 times higher than those obtained from compressibility
      measurements at 298 K and Gruneisen constants derived from the temperature
      dependence of ADPs.

PMID- 17181266
TI  - Excess Gibbs potential model for multicomponent hydrogen clathrates.
AB  - A new thermodynamic calculation procedure is introduced to predict the
      equilibrium conditions of multicomponent gas hydrates containing hydrogen. This
      new approach utilizes an excess Gibbs potential term to account for second- or
      higher-order water-cavity distortions due to the presence of multiple guest
      species. The excess Gibbs potential describes changes in reference chemical
      potentials according to different compositions of guest mixtures in the hydrate
      phase. To determine the equilibrium conditions of multicomponent gas hydrates,
      the excess Gibbs potential term is incorporated to the Lee-Holder model along
      with the Zele-Lee-Holder cell distortion model. For binary gas hydrates between
      hydrogen and the other gas molecule, the predicted equilibrium pressure deviates
      within 10-20% from the experimental value. For the ternary and quaternary mixture
      hydrates, the model prediction is reasonably good but its error increases with
      increasing pressure and temperature under the presence of THF.

PMID- 17181268
TI  - Phase behavior of elemental aluminum using monte carlo simulations.
AB  - Monte Carlo simulations are presented for two models of aluminum: an embedded
      atom model and an explicit many-body model. Vapor/liquid coexistence curves are
      determined using Gibbs ensemble Monte Carlo simulations. The normal boiling
      points predicted by both models are somewhat higher (by about 10%) than the
      experimental value. Isothermal constant-stress simulations are used to simulate
      solid Al from 300 K to the triple point. The solid structures are at least
      metastable in the face-centered cubic configuration, and the specific heat is
      determined to be lower than the experimental value. The melting point for the
      embedded-atom model determined via thermodynamic integration along a pseudo
      supercritical path is approximately 20% higher than the experimental value.

PMID- 17181269
TI  - Kinetic study for the inclusion complex of carboxylic acids with cyclodextrin by
      the ultrasonic relaxation method.
AB  - Ultrasonic absorption coefficients in the frequency range of 0.8-95 MHz were
      measured in aqueous solutions containing both beta-cyclodextrin (beta-CD) (host)
      and butanoic acid (in its dissociated form and undissociated one) (guest). A
      single relaxational phenomenon was observed only when the solutes were
      coexisting, although no relaxation was found in the beta-CD solution or in the
      acid solutions. The absorption was also measured in a solution of pentanoic acid
      (dissociated form) with beta-CD, and single relaxation was detected. The
      ultrasonic relaxation observed in these solutions was due to a perturbation of a
      chemical equilibrium related to a reaction of an inclusion complex formed by the
      host and guest. The equilibrium constant was obtained from the dependence of the
      maximum absorption per wavelength on the guest concentration. The rate constant
      for the inclusion process of the guest into a cavity of beta-CD and that for the
      leaving process from the cavity were determined from the obtained relaxation
      frequency and the equilibrium constant. The standard volume change of the
      reaction was also computed from the maximum absorption per wavelength. These
      results were compared with those in solutions containing both beta-CD and
      different guest molecules. It was found that the hydrophobicity of guest
      molecules played an important role in the formation of the inclusion complex and
      also that the charge on the carboxylic group had a considerable effect on the
      kinetic characteristics of the complexation reaction.

PMID- 17181270
TI  - Crystalline polymorphism and molecular structure of sodium pravastatin.
AB  - In this work different crystallization processes of sodium pravastatin are
      explored and a new polymorph is obtained. The analytical results of powder X-ray
      diffraction (PXRD) and thermal analysis for this new polymorph indicate that it
      is different from the polymorphs previously reported. This new crystal form shows
      different physical-chemical properties than the previous forms, such as
      crystallographic structure, thermal behavior, and melting point, 181.5 degrees C.
      Besides, all crystallization processes previously reported use an aprotic solvent
      as antisolvent. However, we propose a new crystallization process for sodium
      pravastatin that uses only protic solvents, overcoming industrial scaling and
      environmental problems. Variable-temperature PXRD experiments show a
      transformation between different crystal forms in the range of 80-120 degrees C.
      Solid-state 13C NMR, reported in this work for the first time, and Fourier
      transform infrared (FT-IR) studies of some polymorphs show some differences in
      intermolecular interactions, especially with carboxylate and hydroxyl groups.
      Quantum mechanical calculations of the pravastatin molecule are also presented
      for the first time, obtaining a molecular structure similar to the experimental
      structure existing within the crystal lattice of the tert-octylamonium salt of
      pravastatin.

PMID- 17181271
TI  - Role of aerosil dispersion on the activated kinetics of the LC1-xSilx system.
AB  - This study explores the role of aerosil dispersion on activated phase transitions
      of bulk octylcyanobiphenyl (8CB) liquid crystals by performing heating rate
      dependent experiments. Differential scanning calorimetry (DSC) was used at
      various heating ramp rates in order to probe the activated phase dynamics of the
      system. The system, LC1-xSilx, was prepared by mixing aerosil nanoparticles (7 nm
      in diameter) in the bulk 8CB by the solvent dispersion method (SDM). LC
      represents bulk 8CB, and Sil represents aerosil nanoparticles with concentration
      x in percent. The concentration of the aerosil nanoparticles (x) varied from 0 to
      0.2 g/cm3 in the bulk 8CB. Well-defined, endothermic peaks were found on a
      heating scan at melting and at the smectic-A to nematic (SmA-N) and nematic to
      isotropic (N-I) transitions. These peaks show a temperature shift and a change in
      their shapes and sizes in the presence of aerosil nanoparticles. In addition, an
      exothermic peak also appeared before the melting peak during the heating scan in
      the presence of aerosil nanoparticles. All transitions shifted significantly with
      different heating ramp rates, following an Arrhenius behavior, showing activated
      kinetics. The presence of aerosil nanoparticles caused a significant increase in
      the enthalpy and a decrease in the activation energy compared to the results
      found in bulk 8CB. This behavior can be explained by aerosil dispersion in the
      LC1-xSilx, inducing a disorder in the bulk 8CB. Infrared (IR) spectroscopy shows
      a shift to higher frequency for the broad peak at 1082 cm-1, corresponding to an
      Si-O bond as the density of the aerosil increases, and can be explained in terms
      of surface and molecular interactions between aerosil nanoparticles and 8CB
      liquid crystal molecules.

PMID- 17181272
TI  - Synthetic polymers and biomembranes. How do they interact? Atomistic molecular
      dynamics simulation study of PEO in contact with a DMPC lipid bilayer.
AB  - The understanding of interactions of poly(ethylene glycol) (PEG) or poly(ethylene
      oxide) (PEO) with biological interfaces has important technological application
      in industry and in medicine. In this paper, structural and dynamical properties
      of PEO at the dimyristoylphospatidylcholine (DMPC) bilayer/water interface have
      been investigated by molecular dynamics (MD) and steered molecular dynamics (SMD)
      simulations. The structural properties of a PEO chain in bulk water, at the
      water/vacuum interface, and in the presence of the membrane were compared with
      available experimental data. The presence of a barrier for the PEO penetration
      into the DMPC bilayer has been found. A qualitative estimation of the barrier
      provided a value equal to approximately 19 kJ/mol, that is, 7 times the value of
      kT at 310 K.

PMID- 17181273
TI  - The electronic structures of Co and Ni tetraazaannulenes.
AB  - We compare the electronic structure of two metal-centered tetramethyldibenzo
      tetraazaannulene (TMTAA) macrocyclic complex molecules: 5,7,12,14- tetramethyl
      2,3:9,10-dibenzo[b,i]-1,4,8,11-tetraazacyclotetradecine nickel (II) and 5,7,12,14
      tetramethyl-2,3:9,10-dibenzo[b,i]-1,4,8,11-tetraazacyclotetradecine cobalt (II).
      The experimental gap between the highest occupied molecular orbital to the lowest
      unoccupied molecular orbital for both molecules, obtained from combined
      ultraviolet photoemission and inverse photoemission studies, is close to the
      value of 6.6 eV expected from simple model calculations, but with the Fermi level
      placed closer to the lowest unoccupied molecular orbital. While both the Co(II)
      (s = 1/2) and Ni(II) (s = 0) TMTAA molecular electronic structures are very
      similar, the Ni(II) adopts a high-symmetry molecular configuration upon
      adsorption, with a strong preferential orientation.

PMID- 17181274
TI  - Molecular dynamics simulations of hexahydro-1,3,5-trinitro-1,3,5-s-triazine (RDX)
      using a combined Sorescu-Rice-Thompson AMBER force field.
AB  - We present the results of molecular dynamics simulations of crystalline hexahydro
      1,3,5-trinitro-1,3,5-s-triazine (RDX) using the SRT-AMBER force field (P. M.
      Agrawal et al., J. Phys. Chem. B 2006, 110, 5721), which combines the rigid
      molecule force field developed by Sorescu-Rice-Thompson (D. C. Sorescu, B. M.
      Rice, and D. L. Thompson, J. Phys. Chem. B 1997, 101, 798) with the
      intramolecular interactions obtained from the Generalized AMBER Force Field (Wang
      et al., J. Comput. Chem. 2004, 25, 1157). The calculated crystal density at room
      conditions is about 10% lower than the measured value, while the lattice
      parameters and thermodynamic melting point are within about 5% at ambient
      pressure. The chair and inverted chair conformation, bond lengths, and bond
      angles of the RDX molecule are accurately predicted; however, there are some
      inaccuracies in the calculated orientations of the NO2 groups. The SRT-AMBER
      force field predicts overall reasonable results, but modifications, probably in
      the torsional parameters, are needed for a more accurate force field.

PMID- 17181275
TI  - Thermal properties of bi nanowire arrays with different orientations and
      diameters.
AB  - The thermal properties of single-crystalline Bi nanowire arrays with different
      orientations and diameters were studied by differential scanning calorimeter and
      in situ high-temperature X-ray diffraction. Bi nanowires were fabricated by a
      pulsed electrodeposition technique within the porous anodic alumina membrane. The
      relationships between the orientation and diameter of Bi nanowires and the
      corresponding thermal properties are deduced solely from experimental results. It
      is shown that the melting point decreases with decreasing nanowire diameter, and
      there is an anisotropic thermal expansion property of Bi nanowires with different
      orientations and diameters. The transition of the thermal expansion coefficient
      from positive at low temperature to negative at high temperature for Bi nanowire
      arrays was analyzed and discussed.

PMID- 17181276
TI  - Re-entrant nematic behavior in the 7OCB+9OCB mixtures: evidence for multiple
      nematic-smectic tricritical points.
AB  - The metastable phase diagram of the two-component system heptyloxycyanobiphenyl
      (7OCB)+nonyloxycyanobiphenyl (9OCB) was determined by means of modulated
      differential scanning calorimetry (MDSC) and optical microscopy measurements. It
      was experimentally established that the 7OCB+9OCB two-component system exhibits a
      monotropic re-entrant nematic behavior. A complete quantitative thermodynamic
      analysis, through Oonk's equal G analysis, was performed, allowing for the
      calculation of the monotropic re-entrant behavior and the prediction of two
      tricritical points, one of them experimentally accessible for the SmAd-to-N
      transition and the other non-experimentally accessible for the RN-to-SmAd
      transition. From specific-heat measurements, latent heats were obtained for those
      mixtures displaying a first-order SmAd-to-N transition. Additionally, for some
      mixtures, the specific-heat critical exponents (alpha), through the second-order
      SmAd-to-N transition, were obtained. Both batches of data enable us to access to
      the experimental tricritical temperature for the SmAd-to-N transition.

PMID- 17181277
TI  - Isothermal compressibility maxima of hydrogen fluoride in the supercritical and
      superheated vapor regions.
AB  - The highly nonideal behavior of hydrogen fluoride (HF) vapor has been considered
      to be the origin of its numerous vapor phase anomalies. In this work, we report
      one such potential vapor phase anomaly for HF. For a nonassociating substance
      like propane, the response functions go through a maximum only once in the
      supercritical region. However, for HF, when an association model is used to
      predict the isothermal compressibility (KT), it exhibits a maximum in the
      supercritical region more than once, and this peak extends well in to the
      superheated vapor region upon decompression. This theoretical prediction is also
      supported by two other models recently developed for HF. Note that experimental
      values of KT for HF have not been reported in the literature so far. Preliminary
      investigations on this KT maximum for HF have suggested no reentrant spinodal,
      singularity-free scenario, or any additional first-order phase transition, unlike
      water, and, also, no lambda (or higher-order phase) transitions, unlike liquid
      helium. However, this KT peak is similar to the experimentally supported heat
      capacity (CP) peak of HF which extends into the supercritical and superheated
      vapor regions. Similar to the CP peak, which is understood based on vapor-phase
      clustering in HF, we relate KT to the derivatives of enthalpy and entropy of the
      system. Also, we analyze some of the P-v-T experimental data that are available
      to provide an overview of the KT behavior in the region of interest, and compare
      them with the model results. Finally, to explore the effect of including a
      distribution pattern for the oligomers, we report the results on a model that
      only includes association. Using this approach, we report KT results with and
      without a Poisson-type oligomer distribution and show that the KT appears once
      this distribution scheme is specified.

PMID- 17181278
TI  - On enhanced translational diffusion or the fractional Stokes-Einstein relation
      observed in a supercooled ionic liquid.
AB  - From their experimental studies of the supercooled molecular ionic liquid 1-butyl
      3-methylimidazolium hexafluorophosphate (BMIM-HFP), Ito and Richert [J. Phys.
      Chem. B 2006, in press.] found that the Stokes-Einstein and the Debye-Stokes
      Einstein laws do not hold. Instead, enhanced translational diffusion or
      fractional Stokes-Einstein and fractional Debye-Stokes-Einstein relations are
      observed, just like in nonionic glass-forming liquids, including 1,3-bis(1
      naphthyl)-5-(2-naphthyl)benzene, o-terphenyl, and sucrose benzoate. The
      comprehensive measurements made by Ito and Richert have determined the critical
      parameters that the coupling model needs to explain the observed fractional
      Stokes-Einstein and fractional Debye-Stokes-Einstein relations in the supercooled
      molecular ionic liquid.

PMID- 17181279
TI  - Study of the thermal diffusion behavior of alkane/benzene mixtures by thermal
      diffusion forced rayleigh scattering experiments and lattice model calculations.
AB  - In this work the thermal diffusion behavior of binary mixtures of linear alkanes
      (heptane, nonane, undecane, tridecane, pentadecane, heptadecane) in benzene has
      been investigated by thermal diffusion forced Rayleigh scattering (TDFRS) for a
      range of concentrations and temperatures. The Soret coefficient ST of the alkane
      was found to be negative for these n-alkane/benzene mixtures indicating that the
      alkanes are enriched in the warmer regions of the liquid mixtures. For the
      compositions investigated in this work, the magnitude of the Soret coefficient
      decreases with increasing chain length and increasing alkane content of the
      mixtures. The temperature dependence of the Soret coefficient depends on mixture
      composition and alkane chain length; the slope of ST versus temperature changes
      from positive to negative with increasing chain length at intermediate
      compositions. To study the influence of molecular architecture on the Soret
      effect, mixtures of branched alkanes (2-methylhexane, 3-methylhexane, 2,3
      dimethylpentane, 2,4-dimethylpentane, 2,2,3-trimethylbutane, and 2,2,4
      trimethylpentane) in benzene were also investigated. Our results for the Soret
      coefficients show that the tendency for the alkanes to move to the warmer regions
      of the fluid decreases with increasing degree of branching. The branching effect
      is so strong that for 2,2,4-trimethylpentane/benzene mixtures the Soret
      coefficient changes sign at high alkane content and that equimolar 2,2,3
      trimethylbutane/benzene mixtures have positive Soret coefficients in the
      investigated temperature range. In order to investigate the effect of molecular
      interactions on thermal diffusion, we adapted a recently developed two-chamber
      lattice model to n-alkane/benzene mixtures. The model includes the effects of
      chain-length, compressibility, and orientation dependence of benzene-benzene
      interactions and yields good qualitative predictions for the Soret effect in n
      alkane/benzene mixtures. For the branched isomers, we find some correlations
      between the moments of inertia of the molecules and the Soret coefficients. PACS
      numbers: 66.10.Cb, 61.25.Hq.

PMID- 17181280
TI  - Coupling quantum Monte Carlo to a nonlinear polarizable continuum model for
      spherical solutes.
AB  - Starting from the nonlinear dielectric response model of Sandberg and Edholm, we
      derive an analytical expression of the polarization contribution to the solvation
      free energy in terms of the electronic density of the solute and the dielectric
      properties of the solvent. The solvent inhomogeneity is taken into account with
      the use of a smooth switching function whose spacial variation is established on
      the basis of how the solvent is arranged around the solute. An explicit form of a
      local potential representing the solvent effect on the solute is thus obtained by
      functional analysis. This effective potential can be combined with density
      functional or quantum chemical methods for the quantum mechanical treatment of
      the solute. Here, we use quantum Monte Carlo techniques for the solute and apply
      the method to the hydration of atomic ions finding very good agreement with
      experimental data.

PMID- 17181281
TI  - A Monte Carlo study of spherical electrical double layer of macroions
      polyelectrolytes systems in salt free solutions.
AB  - A canonical Monte Carlo simulation is performed to investigate the microstructure
      and the electrical double layer (EDL) of polyelectrolytes around macroions in the
      bulk systems based on the primitive model. We explore the influences of particles
      size, chain length, and charge density of polyelectrolytes on the microscopic
      behavior of the macroions-polyelectrolytes systems. The simulation results show
      that the surface charge density and the chain length of the polyelectrolytes are
      two key factors that affect the microstructure of polyelectrolytes around the
      macroions and potential of mean force between the macroions as well as the zeta
      potential of the spherical EDL constructed by polyelectrolytes. The high surface
      charge density of a polyelectrolyte leads to the polyelectrolyte acting as a
      bridge for the aggregation of macroions, causing the presence of the attraction
      between macroions. The polyelectrolytes with a long chain length present a
      cooperativity effect for the adsorption of the polyelectrolytes on the surface of
      the macroions. Furthermore, the two key factors both induce the overcharge of the
      macroions. The longer the chain length and the higher surface charge density of
      the polyelectrolytes, the stronger is the overcharge.

PMID- 17181282
TI  - Electron-attachment resonances of glycine zwitterions from quantum scattering
      calculations: modeling macrosolvation effects.
AB  - A computational study of the quantum dynamics for low-energy electrons scattered
      by the isolated zwitterionic species of the glycine molecule is carried out using
      a model interaction potential described in the main text. The macroscopic effects
      of water solvation on the target molecule in the electron scattering problem are
      described through a continuum polarizable model (CPCM) which modifies the target
      molecular structure. In such a way, realistic molecular orbitals depicting the
      glycine zwitterion in solution are used to model the electron-molecule
      interaction. The results of the calculations indicate the presence of five
      different transient negative ions (TNIs) formed at energies from the threshold
      and up to about 6 eV. Although no nuclear motion was explicitly considered in the
      ensuing decay processes, the analysis of the nodal structures and density
      distributions for the resonant excess electron wavefunctions over the molecular
      space suggests possible anionic fragmentations that produce (Gly-H)-, H-, -CO2-,
      and -NH3. The likely consequences of such releases into the medium are briefly
      discussed.

PMID- 17181283
TI  - Dynamics of the nitroxide side chain in spin-labeled proteins.
AB  - The dynamics of the tether linking methanethiosulfonate (MTSSL) spin probes to
      alpha-helices has been investigated with the purpose of rationalizing its effects
      on ESR line shapes. Torsional profiles for the chain bonds have been calculated
      ab initio, and steric interactions with the alpha-helix and the neighboring
      residues have been introduced at the excluded-volume level. As a consequence of
      the restrictions deriving from chain geometry and local constraints, a limited
      number of allowed conformers has been identified that undergo torsional
      oscillations and conformational jumps. Torsional fluctuations are described as
      damped oscillations, while transition rates between conformers are calculated
      according to the Langer multidimensional extension of the Kramers theory. The
      time scale and amplitude of the different motions are compared; the major role
      played by rotations of the outermost bonds of the side chain emerges, along with
      the effects of substituents in the pyrroline ring on the conformer distribution
      and dynamics. The extent and symmetry of magnetic tensor averaging produced by
      the side chain motions are estimated, the implications for the ESR spectra of
      spin-labeled proteins are discussed, and suggestions for the introduction of
      realistic features of the spin probe dynamics into the line shape simulation are
      presented.

PMID- 17181285
TI  - Study of gramicidin A--phospholipid interactions in Langmuir monolayers: analysis
      of their mechanical, thermodynamical, and electrical properties.
AB  - The mechanisms of interactions between gramicidin A (gA) and
      dimyristoylphosphatidylcholine (DMPC) in monolayers formed at the air-water
      interface were studied by analyzing their mechanical, thermodynamical, and
      electrical properties evaluated from measurements of pressure-area isotherms and
      of Maxwell displacement currents (MDC). A contactless method of recording MDC
      enabled us to monitor changes in the charge state of the monolayer-constituting
      molecules and to find the relation between a phase state of the monolayer and
      structural transitions of gA. The peptide-lipid interactions were quantified in
      terms of the excess of Gibbs free energy, excess entropy, as well as the
      molecular dipole moments at various gA/DMPC molar ratios, at various temperatures
      (in the gel phase and also in the liquid-crystalline phase of DMPC molecule), and
      at various surface pressures. It was found that the strongest interactions
      between gA and DMPC took place at the gA/DMPC molar ratio at around 0.25. At this
      monolayer composition, the phospholipids, via their carbonyl moieties, dominantly
      interact with the single helical gA, which mostly stands upright on the surface
      and is anchored by its C-terminus to the water surface, and prevent the formation
      of the intertwined helical gA dimers. The optimum ratio was confirmed also by
      anomalous electrical behavior of electrical dipole moments derived from MDC
      measurements.

PMID- 17181284
TI  - Modeling the effects of structure and dynamics of the nitroxide side chain on the
      ESR spectra of spin-labeled proteins.
AB  - In the companion paper (J. Phys. Chem. B 2006, 110, jp0629487), a study of the
      conformational dynamics of methanethiosulfonate spin probes linked at a surface
      exposed alpha-helix has been presented. Here, on the basis of this analysis, X
      band ESR spectra of these spin labels are simulated within the framework of the
      Stochastic Liouville equation (SLE) methodology. Slow reorientations of the whole
      protein are superimposed on fast chain motions, which have been identified with
      conformational jumps and fluctuations in the minima of the chain torsional
      potential. Fast chain motions are introduced in the SLE for the protein
      reorientations through partially averaged magnetic tensors and relaxation times
      calculated according to the motional narrowing theory. The 72R1 and 72R2 mutants
      of T4 lysozyme, which bear the spin label at a solvent-exposed helix site, have
      been taken as test systems. For the side chain of the R2 spin label, only a few
      noninterconverting conformers are possible, whose mobility is limited to
      torsional fluctuations, yielding almost identical spectra, typical of slightly
      mobile nitroxides. In the case of R1, more complex spectra result from the
      simultaneous presence of constrained and mobile chain conformers, with relative
      weights that can depend on the local environment. The model provides an
      explanation for the experimentally observed dependence of the spectral line
      shapes on temperature, solvent, and pattern of substituents in the pyrroline
      ring. The relatively simple methodology presented here allows the introduction of
      realistic features of the spin probe dynamics into the simulation of ESR spectra
      of spin-labeled proteins; moreover, it provides suggestions for a proper account
      of such dynamics in more sophisticated approaches.

PMID- 17181286
TI  - Cylindrical inclusions in a copolymer membrane.
AB  - The membrane-mediated interaction between two parallel, cylindrical inclusions is
      investigated by using the self-consistent field theory (SCFT). The rodlike
      inclusions are located within the interior of the bilayer and are enveloped by
      two monolayers. They may exhibit one of the two basic types of behaviors
      involving pinching two monolayers together and swelling them outward. For
      different parameters, we calculate the density profile of the deformation
      membrane, the associated interaction free energy, as well as the conformational
      entropy of polymer chains. The similarity of the two types of interaction
      potentials is the qualitative characteristics. An energy barrier separates an
      attractive from a repulsive region; the repulsive region is preceded by a weak
      attraction at a large distance. The difference between them, which is due to the
      different contact environments around the rods, lies in the appearance of a small
      barrier at a short distance in the pinching structure. Particular emphasis is put
      on the closely energetic and entropic analyses of the interaction potential. We
      show that the chemical potential energy has provided a qualitative trend and
      roughly dominated the basic shape of the interaction potential; the amphiphile
      entropy in the swelling structure and the solvent entropy in the pinching
      structure, combined with the corresponding chemical potential energy, are
      responsible for the repulsive barrier at an intermediate distance and for the
      weak attraction at a large distance, respectively. The influence of inclusion
      hydrophobicity on the interaction potential is taken into account. In particular,
      the pinching and swelling structures can appear and can transform into each other
      in a system at intermediate hydrophobicity.

PMID- 17181288
TI  - Nanosecond relaxation dynamics of protein GB1 identified by the time-dependent
      red shift in the fluorescence of tryptophan and 5-fluorotryptophan.
AB  - The B1 domain of Streptococcal protein G (GB1) is a small, thermostable protein
      containing a single tryptophan residue. We recorded time-resolved fluorescence of
      the wild-type GB1 and its 5-fluorotryptophan (5FTrp) variant at more than 30
      emission wavelengths between 300 and 470 nm. The time-resolved emission spectra
      reveal no signs of heterogeneity, but show a time-dependent red shift
      characteristic of microscopic dielectric relaxation. This is true for both 5FTrp
      and unmodified Trp in GB1. The time-dependent red shifts in the fluorescence of
      5FTrp and unmodified Trp are essentially identical, confirming that the shift is
      caused by the relaxation of the protein matrix rather than by the fluorophore
      itself. The total amplitude (but not the rate) of the time-dependent red shift
      depends on the fluorophore, specifically, on the magnitude of the vector
      difference between its excited state and ground state electric dipole moments;
      for 5FTrp this is estimated to be about 88% of that for the unmodified Trp. The
      decay of the excited state fluorophore population is not monoexponential for
      either fluorophore; however, the deviation from the monoexponential decay law is
      larger in the case of unmodified Trp. The relaxation dynamics of GB1 was found to
      be considerably faster than that of other proteins studied previously, consistent
      with the small size, tightly packed core, and high thermodynamic stability of
      GB1.

PMID- 17181287
TI  - An investigation into the mechanisms of DNA strand breakage by direct ionization
      of variably hydrated plasmid DNA.
AB  - The mechanisms by which ionizing radiation directly causes strand breaks in DNA
      were investigated by comparing the chemical yield of DNA-trapped free radicals to
      the chemical yield of DNA single strand break (ssb) and double strand break
      (dsb), as a function of hydration (Gamma). Solid-state films of plasmid pUC18,
      hydrated to 2.5 < Gamma < 22.5 mol, were X-irradiated at 4 K, warmed to room
      temperature, and dissolved in water. Free radical yields were determined by EPR
      at 4 K. With use of the same samples, Gel electrophoresis was used to measure the
      chemical yield of total strand breaks, which includes prompt plus heat labile
      ssb; G'total(ssb) decreased from 0.092 +/- 0.016 micromol/J at Gamma= 2.5 to
      0.066 +/- 0.008 micromol/J at Gamma= 22.5. Most provocative is that at Gamma= 2.5
      the yield of total ssb exceeds the yield of trapped deoxyribose radicals:
      G'total(ssb) - G'sugar(fr) = 0.06 +/- 0.02 micromol/J. Nearly 2/3 of the strand
      breaks are derived from precursors other than radicals trapped on the deoxyribose
      moiety. To account for these nonradical precursors, we hypothesize that strand
      breaks are produced by two one-electron oxidations at a single deoxyribose
      residue within an ionization cluster.

PMID- 17181289
TI  - One- and two-color photon echo peak shift studies of photosystem I.
AB  - Wavelength-dependent one- and two-color photon echo peak shift spectroscopy was
      performed on the chlorophyll Qy band of trimeric photosystem I from
      Thermosynechococcus elongatus. Sub-100 fs energy transfer steps were observed in
      addition to longer time scales previously measured by others. In the main PSI
      absorption peak (675-700 nm), the peak shift decays more slowly with increasing
      wavelength, implying that energy transfer between pigments of similar excitation
      energy is slower for pigments with lower site energies. In the far-red region
      (715 nm), the decay of the peak shift is more rapid and is complete by 1 ps, a
      consequence of the strong electron-phonon coupling present in this spectral
      region. Two-color photon echo peak shift data show strong excitonic coupling
      between pigments absorbing at 675 nm and those absorbing at 700 nm. The one- and
      two-color peak shifts were simulated using the previously developed energy
      transfer model (J. Phys. Chem. B 2002, 106, 10251; Biophysical Journal 2003, 85,
      140). The simulations agree well with the experimental data. Two-color photon
      echo peak shift is shown to be far more sensitive to variations in the molecular
      Hamiltonian than one-color photon echo peak shift spectroscopy.

PMID- 17181290
TI  - Exploring the binding of serotonin to the 5-HT3 receptor by density functional
      theory.
AB  - The 5-HT3 receptor is a typical ligand-gated ion channel of the Cys-loop
      superfamily, which is activated by binding of serotonin (5-HT). Models of the
      binding site of this protein reveal potential interactions between 5-HT and
      Tyr143, Tyr153, and Tyr234. Here we describe a series of ab initio calculations,
      based on density functional theory, to assess the effects of mutating these
      tyrosine residues on the binding of 5-HT. A series of mutations to these
      tyrosines, previously studied experimentally, were tested, and the binding
      energies compared with the available experimental data. Our results show that
      Tyr153 could form a hydrogen bond with the tertiary amine of 5-HT, and that
      mutation in this location revealed binding energies broadly in line with
      experimentally determined EC50s. Tyr143 could also form a hydrogen bond, but as
      EC50s do not relate to binding energies, it is unlikely that such a bond is
      formed here. Tyr234 is quite distinct in that it may interact with 5-HT via a
      mixed hydrogen bond/cation-pi interaction.

PMID- 17181291
TI  - A combined ONIOM quantum chemical-molecular dynamics study of zinc-uracil bond
      breaking in yeast cytosine deaminase.
AB  - A QM/MM method that combines ONIOM quantum chemistry and molecular dynamics is
      developed and applied to a step in the deamination of cytosine to uracil in yeast
      cytosine deaminase (yCD). A two-layer ONIOM calculation is used for the reaction
      complex, with an inner part treated at a high level for the chemical reaction
      (bond breaking) and a middle part treated at a lower level for relevant protein
      residues that are frozen in the quantum optimization. An outer layer (protein and
      solvent) is treated using MD. Configurations for the entire system are generated
      using MD and optimized with ONIOM. The method permits the use of high-level
      quantum calculations along with sufficient configurational sampling to
      approximate the potential of mean force for certain bond-breaking reactions. A
      previously proposed reaction mechanism for deamination (Sklenak, S.; Yao, L. S.;
      Cukier, R. I.; Yan, H. G. J. Am. Chem. Soc. 2004, 126, 14879) requires breaking
      the bond between a catalytic zinc and the O4 of uracil in order to permit product
      release. Using an ONIOM approach, direct bond cleavage was found to be
      energetically unfavorable. In the work presented here, the combined ONIOM MD
      method is used to show that the barrier for bond cleavage is small, approximately
      3 kcal/mol, and, consequently, should not be the rate-limiting step in the
      reaction.

PMID- 17181292
TI  - Excited-state properties and transitions of fluorescent 8-vinyl adenosine in DNA.
AB  - 8-vinyl-adenosine (8VA) is a new fluorescent nucleoside analogue with improved
      spectroscopic properties as compared to 2-aminopurine (2AP). To further
      understand its photophysics, we analyzed by the time-dependent density functional
      theory and the configuration interaction single method, the electronic
      properties, and transitions of 8VA in its free form and stacked with one or two
      flanking bases. For free 8VA, the predicted excited-state energy gaps, absorbance
      peak position, and oscillator strength were found to be in excellent agreement
      with the experimentally determined ones. Moreover, its high fluorescence quantum
      yield was found to be associated with the dipole-allowed S1 --> S0 transition.
      Stacking of 8VA with C, T, or A in dimers or trimers resulted in fluorescence
      quenching through mechanisms that depend on the nature and relative orientation
      of the flanking base(s). When 8VA is stacked with T, quenching mainly results
      from nonradiative relaxation to low-lying dark excited state(s) that do not exist
      in free 8VA. When 8VA is stacked with A, quenching results mainly from mixing of
      the molecular orbitals in the ground state. Both types of quenching are thought
      to accompany the stacking of 8VA with C. In addition, the C-8VA-C trimer was
      found to exhibit a low-lying S1 emissive state that may generate an increased
      fluorescence quantum yield and lifetime. The predicted photophysical properties
      of the trimers are highly consistent with the spectroscopic data of a series of
      15-mer oligonucleotides differing only by the nature of the residues flanking the
      central 8VA.

PMID- 17181293
TI  - Stability and migration of metal ions in G4-wires by molecular dynamics
      simulations.
AB  - We present a molecular dynamics investigation of guanine quadruple helices based
      on classical force fields. We analyze the dependence of the helical conformation
      on various compositional factors, such as the length of the G4-wire, as well as
      the incorporation into the helix channel of alkali ions of different species and
      in different amounts. In compliance with previous indications, our results
      suggest that monovalent alkali cations assist the stability of the quadruplex
      arrangement against disruption on the few nanoseconds time scale in the order of
      increasing van der Waals radius. Whereas very short G4-wire fragments immediately
      unfold in the absence of coordinating metal ions or in the presence of tiny ions
      (e.g., Li+) in agreement with the experimental evidence that empty short guanine
      quadruplexes are not formed in any synthetic conditions, our simulations show
      that longer empty helices do not discompose. This finding supports the
      possibility of producing long G4-wires with different guanine-cation
      stoichiometries than those routinely known. The classical trajectories allow us
      to identify different stationary axial sites for the different metal species,
      which are confirmed by complementary quantum calculations.

PMID- 17181294
TI  - DNA-based molecular wires: multiple emission pathways of individual constructs.
AB  - The extent of photon energy transfer through individual DNA-based molecular wires
      composed of five dyes is investigated at the single molecular level. Combining
      single-molecule spectroscopy and pulse interleaved excitation imaging, we have
      directly resolved the time evolution spectral response of individual constructs,
      while simultaneously probing DNA integrity. Our data clearly show that intact
      wires exhibit photon-transfer efficiencies close to 100% across five dyes.
      Dynamical and multiple pathways for the photon emission resulting from
      conformational freedom of the wire are readily uncovered. These results provide
      the basis for guiding the synthesis of DNA-based supramolecular arrays with
      improved photon transport at the nanometer scale.

PMID- 17181295
TI  - Proton antenna effect of the gamma-cyclodextrin outer surface, measured by
      excited state proton transfer.
AB  - The reversible proton dissociation and geminate recombination of the common
      photoacid, 8-hydroxypyrene-1,3,6-trisulfonate (pyranine), either in dilute
      aqueous solution or when forming a complex with gamma-cyclodextrin (gamma-CD),
      has been studied by time-resolved fluorescence spectroscopy and supplemented by
      molecular modeling and dynamics simulations. We find that the dissociation rate
      of the proton from the excited molecule was decreased to about approximately 50%
      of its value in water, while the rate of recombination was doubled. These
      observations were evaluated by molecular modeling of the reactants at atomic
      resolution. The combination of the two methodologies indicates that the pyranine
      in the complex can assume more than one level of interaction with the solvent.
      The polysugar torus surrounding the pyranine perturbs the hydrogen bond in the
      dye's immediate vicinity and deforms the electrostatic potential inside the
      Coulomb cage, causing major deviations from a simple spheric symmetry. These
      observations can account for the special kinetic features measured for the
      complex. We suggest that this system can be used as a basic model for evaluating
      the mechanism of proton transfer in non-homogeneous systems, such as the surface
      of proteins or biomembranes.

PMID- 17181296
TI  - Microscopic modes and free energies of 3-phosphoinositide-dependent kinase-1
      (PDK1) binding with celecoxib and other inhibitors.
AB  - Celecoxib, also known as Celebrex (approved by FDA in 1998) and remembered as the
      fastest-selling drug in history, was used as a cyclooxygenase-2 (COX-2) selective
      inhibitor having both anti-inflammatory and anticancer activities. Most recent
      studies have revealed that the apoptotic activity of celecoxib (and its
      derivatives) is actually independent of the COX-2 inhibitory activity and that
      celecoxib also inhibits the kinase activity of 3-phosphoinositide-dependent
      protein kinase-1 (PDK1), suggesting that the well-known anticancer activity of
      celecoxib is not due to the inhibition of COX-2, but possibly is due to the
      inhibition of PDK1. It is highly desirable to develop new celecoxib derivatives
      as PDK1-specifc inhibitors to avoid the side effects of COX-2 inhibitors. To
      understand how PDK1 binds with celecoxib and its derivatives, we have performed
      extensive molecular docking and combined molecular dynamics (MD) simulations and
      molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) binding free energy
      calculations on eight representative PDK1 inhibitors, leading to the finding of a
      new, more favorable binding mode which is remarkably different from the
      previously proposed binding mode. Based on the determined most stable binding
      structures, the calculated binding free energies are all in good agreement with
      the corresponding experimental data, and the biological activity data available
      for celecoxib and its derivatives can be better interpreted. The obtained new
      insights, concerning both the binding mode and computational protocol, will be
      valuable not only for future rational design of novel, more potent PDK1-specific
      inhibitors as promising anticancer therapeutics, but also for rational design of
      drugs targeting other proteins.

PMID- 17181297
TI  - Molecular recognition in cyclodextrin complexes of amino acid derivatives: the
      effects of kinetic energy on the molecular recognition of a pseudopeptide in a
      nonconstraining host environment as revealed by a temperature-dependent
      crystallographic study.
AB  - The crystal structure of a triclinic 2:2 inclusion complex of beta-cyclodextrin
      with N-acetyl-L-phenylalanine methyl ester has been determined at several
      temperatures between 298 and 20 K to further study molecular recognition using
      solid-state supramolecular beta-cyclodextrin complexes. The study reveals kinetic
      energy dependent changes in guest molecule conformations, orientations, and
      positions in the binding pocket presented by the crystal lattice. Accompanying
      these changes are observable differences in guest-guest interactions and hydrogen
      bonding interactions in the binding pocket that involve guest molecules, water of
      hydration molecules, and beta-cyclodextrin molecules. On the basis of the
      differences observed in the crystal structures, we present a solid-state example
      of a system that displays the properties of both classical and quantum chemical
      models. At higher temperatures, the structure conforms to a classical mechanical
      model with dynamic disorder. At lower temperatures, the observations conform to
      examples in which there is static disorder representative of models in which
      quantum states differing in conformation, position, and orientation of components
      in the crystal structure are occupied. Ab initio theoretical calculations on the
      different guest molecule conformations have been carried out. Superpositions of
      theoretical electrostatic surface potential diagrams on the observed molecular
      positions in the complexes provide confidence that the deconvolution of the guest
      molecule disorder is acceptable. Temperature-dependent solid-state magic angle
      spinning deuteron NMR measurements provide evidence for large-amplitude,
      diffusive motion on a microsecond time scale in the complex.

PMID- 17181298
TI  - Dimerization and double proton transfer-induced tautomerism of 4(3H)-pyrimidinone
      in solution studied by IR spectroscopy and quantum chemical calculations.
AB  - The tautomerism and dimerization of 4(3H)-pyrimidinone (4(3H)Pyr) in carbon
      tetrachloride (CCl4) and chloroform (CHCl3) solutions were investigated using IR
      spectroscopy and quantum chemical calculations. The observed IR spectra in the NH
      and OH stretching regions clearly revealed the predominance of the keto tautomer
      in both solvent systems. The enol form only exists in a very small proportion in
      the CCl4 solution. The tautomeric constant for the two monomers KT[OH/NH] = 0.012
      and DeltaE = 2.62 kcal/mol were estimated at 25 degrees C. This result was
      supported by the self-consistent reaction field/polarizable continuum (SCRF/PCM)
      calculation at the MP4(full, SDQ)/aug-cc-pVDZ level, which predicted DeltaE =
      3.06 kcal/mol in CCl4. In the C=O stretching region, two bands were observed,
      suggesting the coexistence of two keto structures at equilibrium. The calculated
      IR spectra indicated that the bands at 1711 and 1675 cm(-1) arise from the keto
      monomer and keto-keto (KK) ring dimer, respectively. At elevated temperature, the
      populations of both the keto and enol monomers increased for the CCl4 solution.
      The present study revealed that the keto <--> enol tautomerization does not occur
      in the isolated monomer molecule. The double proton transfer (DPT) reaction in
      the KK ring dimer presumably plays a substantial role in the population increase
      of the enol monomer. To our knowledge, this may be the first observation of the
      tautomerization in a model base pair via the temperature-induced ground-state DPT
      reaction under a nonpolar liquid environment reported so far. This tautomerism
      can serve as a mimic circumstance for the spontaneous mutations induced by proton
      transfer in the DNA base pairs.

PMID- 17181299
TI  - Multiple time scales in solvation dynamics of DNA in aqueous solution: the role
      of water, counterions, and cross-correlations.
AB  - Recent time domain experiments have explored solvation dynamics of a probe
      located inside a DNA duplex, in an effort to gain information, e.g., on the
      dynamics of water molecules in the DNA major and minor grooves and their
      environment. Multiple time constants in the range of a few picoseconds to several
      nanoseconds were obtained. We have carried out 15 ns long atomistic molecular
      dynamics simulations to study the solvation dynamics of bases of a 38 base-pair
      long DNA duplex in an aqueous solution containing counterions. We have computed
      the energy-energy time correlation function (TCF) of the four individual bases
      (A, T, G, and C) to characterize the solvation dynamics. All the TCFs display
      highly nonexponential decay with time. When the trajectories are analyzed with
      100 fs time resolution, the TCF of each base shows initial ultrafast decay (with
      tau1 approximately equal 60-80 fs) followed by two intermediate components (tau2
      approximately equal 1 ps, tau3 approximately equal 20-30 ps), in near complete
      agreement with a recent time domain experiment on DNA solvation. Interestingly,
      the solvation dynamics of each of the four different nucleotide bases exhibit
      rather similar time scales. To explore the existence of slow relaxation at longer
      times reported recently in a series of experiments, we also analyzed the
      solvation TCFs calculated with longer time trajectories and with a larger time
      resolution of 1 ps. In this case, an additional slow component with a time
      constant of the order of 250 ps is observed. Through an analysis of partial
      solvation TCFs, we find that the slow decay originates mainly from the
      interaction of the nucleotides with the dipolar water molecules and the
      counterions. An interesting negative cross-correlation between water and
      counterions is observed, which makes an important contribution to relaxation at
      intermediate to longer times.

PMID- 17181300
TI  - Dynamic competition between catch and slip bonds in selectins bound to ligands.
AB  - Atomic force measurements of unbinding rates (or off-rates) of ligands bound to a
      class of cell adhesion molecules from the selectin family show a transition from
      catch to slip bonds as the value of external force (f) is increased. At low
      forces (<10 pN), the unbinding rates decrease (catch regime), while, at high
      forces, the rates increase in accord with the Bell model (slip regime). The
      energy landscape underlying the catch-slip transition can be captured by a two
      state model that considers the possibility of redistribution of population from
      the force-free bound state to the force-stabilized bound state. The excellent
      agreement between theory and experiments is used to extract the parameters
      characterizing the energy landscape of the complex by fitting the calculated
      curves to lifetime data (obtained at constant f) for the monomeric form of PSGL-1
      (sPSGL-1). We used the constant force parameters to predict the distributions of
      unbinding times and unbinding forces as a function of the loading rate. The
      general two-state model, which also correctly predicts the absence of catch bonds
      in the binding of antibodies to selectins, is used to resolve the energy
      landscape parameters characterizing adhesive interactions of P- and L-selectins
      with physiological ligands such as sPSGL-1 and endoglycan and antibodies such as
      G1 and DREG56. Despite high sequence similarity, the underlying shapes of the
      energy landscape of P-selectin and L-selectin interacting with sPSGL-1 are
      markedly different. The underlying energy landscape of the selectin cell adhesion
      complex is sensitive to the nature of the ligand. The unified description of
      selectins bound to physiological ligands and antibodies in conjunction with
      experimental data can be used to extract the key parameters that describe the
      dynamics of cell adhesion complexes.

PMID- 17181301
TI  - Photoinduced intramolecular electron-transfer reactions of reconstituted met- and
      zinc-myoglobins appending acridine and methylacridinium ion as DNA-binders.
AB  - Three types of reconstituted met- and zinc-myoglobin (metMb and ZnMb) dyads,
      ZnMbAc(4)Me+, ZnMbAc(6)Me+, and metMbAc(6) have been prepared by incorporating
      chemically modified metalloporphyrin cofactor appending an acridine (Ac) or a
      methylacridinium ion ([AcMe]+) into apo-Mb. In the bimolecular system between
      ZnMb and [AcMe]+, the photoexcited triplet state of ZnMb, 3(ZnMb)*, was
      successfully quenched by [AcMe]+ to form the radical pair of ZnMb cation (ZnMb*+)
      and reduced methylacridine ([AcMe]*), followed by a thermal back ET reaction. The
      rate constants for the intermolecular quenching ET (kq) and the back ET reaction
      (kb) at 25 degrees C were successfully obtained as kq = (8.8 +/- 0.4) x 10(7) M(
      1) s(-1) and kb = (1.2 +/- 0.1) x 10(8) M(-1) s(-1), respectively. On the other
      hand, in case of the intramolecular photoinduced ET reactions of ZnMbAc(4)Me+ and
      ZnMbAc(6)Me+ dyads, the first-order quenching rate constants (kET) of 3(ZnMb)* by
      [AcMe]+ moiety were determined to be kET = 2.6 x 10(3) and 2.5 x 10(3) s(-1),
      respectively. When such ET occurs along the alkyl spacer via through-bond
      mechanism at the surface of Mb, the obtained kET is reasonable to provide decay
      constant of beta (1.0-1.3 A(-1)). Upon photoirradiation of [AcMe]+ moiety,
      kinetic studies also presented the intramolecular quenching reactions from the
      excited singlet state, 1([AcMe]+)*, whose likely process is the photoinduced
      energy-transfer reaction. For metMbAc(6) dyad, steady-state fluorescence was
      almost quenched, while the signal around 440 nm gradually appeared in the
      presence of various concentrations of DNA. Our study implies that synthetic
      manipulation at the Mb surface, by using an artificial DNA-binder coupled with
      photoinduced reaction, may provide valuable information to construct new Mb-DNA
      complex and sensitive fluorescent for DNA.

PMID- 17181302
TI  - Investigation of sol-gel transition in pluronic F127/D2O solutions using a
      combination of small-angle neutron scattering and monte carlo simulation.
AB  - Physical gelation in the concentrated Pluronic F127/D2O solution has been studied
      by a combination of small-angle neutron scattering (SANS) and Monte Carlo
      simulation. A 15% F127/D2O solution exhibits a sol-gel transition at low
      temperature and a gel-sol transition at the higher temperature, as evidenced by
      SANS and Monte Carlo simulation studies. Our SANS and simulation results also
      suggest that the sol-gel transition is dominated by the formation of a percolated
      polymer network, while the gel-sol transition is determined by the loss of bound
      solvent. Furthermore, different diffusion behaviors of different bound solvents
      and free solvent are observed. We expect that this approach can be further
      extended to study phase behaviors of other systems with similar sol-gel phase
      diagrams.

PMID- 17181303
TI  - Electrochemical and PM-IRRAS studies of the effect of cholesterol on the
      properties of the headgroup region of a DMPC bilayer supported at a Au(111)
      electrode.
AB  - Polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS)
      was employed to investigate the interaction of cholesterol with the headgroups of
      dimyristoylphosphatidycholine (DMPC) molecules under a static electric field.
      DMPC/cholesterol (7:3 molar ratio) mixtures form a bilayer on a Au(111) electrode
      surface by fusion and spreading of small unilamellar vesicles. PM-IRRAS
      experiments provided detailed information concerning the conformation and
      hydration of headgroups of DMPC bilayers in the presence and absence of 30%
      cholesterol. The presence of 30% cholesterol increases the space between the
      headgroups of DMPC molecules and hence increases the hydration of the
      DMPC/cholesterol mixed bilayer. The conformational state of the headgroups of
      DMPC molecules in the mixed bilayer is also significantly changed. The phosphate
      group is closer to the surface compared with the pure DMPC bilayer. The
      conformation of the -O-C-C-N moiety changes from gauche to trans in the presence
      of cholesterol.

PMID- 17181304
TI  - Experimental charge density study of estrogens: 17beta-estradiol.urea.
AB  - To relate the molecular electrostatic potential to the biological activities of
      estrogens, a comparative charge density study of different derivatives has been
      initiated. The second completed charge density analysis of this series for 17beta
      estradiol*urea is presented here. This is a large organic system with 52 atoms in
      a noncentrosymmetric space group, therefore special tools such as an optimal
      coordinate system and slow, initially constrained refinement have been used to
      accomplish this study. Our results for the urea molecule reasonably agree with
      previous experimental and theoretical results. In the 17beta-estradiol molecule,
      the oxygen atoms appear to be close to sp3 in shape, exhibiting two consistent,
      distinct lone pairs despite different chemical environments. No significant
      interaction of the hydroxyl group oxygen with the orbitals of the aromatic ring
      is observed. Analysis of the electrostatic potential revealed that the negative
      potential in the lone pair region of the two oxygen atoms is quite different. The
      topological analysis of the electron density has been performed, and the atomic
      charges have been estimated.

PMID- 17181305
TI  - Steered molecular dynamics studies of the potential of mean force of a Na+ or K+
      ion in a cyclic peptide nanotube.
AB  - Potential of mean force (PMF) profiles of a single Na+ or K+ ion passing through
      a cyclic peptide nanotube, cyclo[-(D-Ala-Glu-D-Ala-Gln)2-], in water are
      calculated to provide insight into ion transport and to understand the
      conductance difference between these two ions. The PMF profiles are obtained by
      performing steered molecular dynamics (SMD) simulations that are based on the
      Jarzynski equality. The computed PMF profiles for both ions show barriers of
      around 2.4 kcal/mol at the channel entrances and exits and energy wells in the
      middle of the tube. The energy barriers, so-called dielectric energy barriers,
      arise due to the desolvation of water molecules when ions move across the
      nanotube, and the energy wells appear as a result of attractive interactions
      between the cations and negatively charged carbonyl oxygens on the backbone of
      the tube. We find more and deeper energy wells in the PMF profile for Na+ than
      for K+, which suggests that Na+ ions have a longer residence time inside the
      nanotube and that permeation of Na+ ions is reduced compared to K+ ions.
      Calculations of the radial distribution functions (RDF) between the ions and
      oxygens in the water molecules and in carbonyl groups on the tube and an
      investigation of the orientations of the carbonyl groups show that, in contrast
      with the dynamic carbonyl groups observed in the selectivity filter of the KcsA
      ion channel, the carbonyl groups in the cyclic peptide nanotube are relatively
      rigid, with only slight reorientation of the carbonyl groups as the cations pass
      through. The rigidity of the carbonyl groups in the cyclic peptide nanotube can
      be attributed to their role in hydrogen bonding, which is responsible for the
      tube structure. Comparison of the PMF profiles with the electrostatic energy
      profiles calculated from the Poisson-Boltzmann (PB) equation, a dielectric
      continuum model, reveals that the dielectric continuum model breaks down in the
      confined region within the tube that governs ion transport.

PMID- 17181306
TI  - Chlorine-35/37 NMR spectroscopy of solid amino acid hydrochlorides: refinement of
      hydrogen-bonded proton positions using experiment and theory.
AB  - Trends in the chlorine chemical shift (CS) tensors of amino acid hydrochlorides
      are investigated in the context of new data obtained at 21.1 T and extensive
      quantum chemical calculations. The analysis of chlorine-35/37 NMR spectra of
      solid L-tryptophan hydrochloride obtained at two magnetic field strengths yields
      the chlorine electric field gradient (EFG) and CS tensors, and their relative
      orientations. The chlorine CS tensor is also determined for the first time for DL
      arginine hydrochloride monohydrate. The drastic influence of 1H decoupling at
      21.1 T on the spectral features of salts with particularly small 35Cl quadrupolar
      coupling constants (CQ) is demonstrated. The chlorine CS tensor spans (Omega) of
      hydrochloride salts of hydrophobic amino acids are found to be larger than those
      for salts of hydrophilic amino acids. A new combined experimental-theoretical
      procedure is described in which quantum chemical geometry optimizations of
      hydrogen-bonded proton positions around the chloride ions in a series of amino
      acid hydrochlorides are cross-validated against the experimental chlorine EFG and
      CS tensor data. The conclusion is reached that the relatively computationally
      inexpensive B3LYP/3-21G* method provides proton positions which are suitable for
      subsequent higher-level calculations of the chlorine EFG tensors. The computed
      value of is less sensitive to the proton positions. Following this cross
      validation procedure, /CQ(35Cl)/ is generally predicted within 15% of the
      experimental value for a range of HCl salts. The results suggest the
      applicability of chlorine NMR interaction tensors in the refinement of proton
      positions in structurally similar compounds, e.g., chloride ion channels, for
      which neutron diffraction data are unavailable.

PMID- 17181307
TI  - Unified model for the ultrafast decay of pyrimidine nucleobases.
AB  - Ultrafast decay processes detected after absorption of UV radiation in gas-phase
      pyrimidine nucleobases uracil, thymine, and cytosine are ascribed to the
      barrierless character of the pathway along the low-lying 1(pipi*) hypersurface
      connecting the Franck-Condon region with an out-of-plane distorted ethene-like
      conical intersection with the ground state. Longer lifetime decays and low
      quantum yield emission are on the other hand related to the presence of a
      1(pipi*) state planar minimum on the S1 surface and the barriers to access other
      conical intersections. A unified model for the three systems is established on
      the basis of accurate multiconfigurational CASPT2 calculations, whereas the
      effect of the different levels of theory on the results is carefully analyzed.

PMID- 17181308
TI  - Mossbauer study and magnetic properties of M-type barium hexaferrite doped with
      Co + Ti and Bi + Ti ions.
AB  - Using X-ray powder diffractions, Mossbauer spectroscopy, and magnetic
      measurements, the effect of complex dopants (Co2+ + Ti4+) and (Bi3+ + Ti4+) on
      the fine structure and magnetic properties of M-type barium hexaferrite prepared
      by hydroxide and carbonate precipitations has been studied. The distribution of
      cations over five nonequivalent positions of barium hexaferrite with
      magnetoplumbite structure is discussed. It has been shown that doped barium
      hexaferrite can be used for high-coercitivity data storage media.

PMID- 17181309
TI  - Modified lithium borohydrides for reversible hydrogen storage (2).
AB  - This paper reports the results of the effort to destabilize lithium borohydride
      for reversible hydrogen storage. Various metals, metal hydrides, and metal
      chlorides were selected and evaluated as destabilization agents for reducing
      dehydriding temperatures and improving dehydriding/rehydriding reversibility. The
      most effective material was LiBH4 + 0.2MgCl2 + 0.1TiCl3 which starts desorbing 5
      wt % of hydrogen at 60 degrees C and can be rehydrogenated to 4.5 wt % at 600
      degrees C and 70 bar. X-ray diffraction and Raman spectroscopic analysis show the
      interaction of LiBH4 with additives and the unusual change of B-H stretching.

PMID- 17181310
TI  - Theoretical investigation of static characterization on nonlinear elementary
      excitations in trans-polyacetylene.
AB  - Semiempirical quantum chemical studies on neutral and positively charged H(CH)nH
      homologues have been performed for systems with n up to 101, where different
      kinds of nonlinear excitation are found with increasing chain length. The Pariser
      Parr-Pople (PPP) model has been employed and solved with the density matrix
      renormalization group (DMRG) method. The geometrical and electronic distortions
      induced by defects are obtained and compared with previous theoretical work,
      indicating that an adequate account of the electron correlation is essential for
      describing such systems. The structural distortion of a charged soliton (half
      width calculated as L = 13) is shown to be more extended than that of a neutral
      soliton (L = 6); the geometrical distortion is even more extended in a polaron.
      In bipolarons, our calculations show that the coupling of the soliton-antisoliton
      pair might be longer ranged than expected. The phase transition from a bipolaron
      to a separated soliton-antisoliton pair occurs when n is close to 100.

PMID- 17181311
TI  - Photexcitation of aqueous ruthenium(II)-tris-(2,2'-bipyridine) with high
      intensity femtosecond laser pulses.
AB  - We report a femtosecond pump-probe study on the photochemistry of concentrated
      aqueous solutions of [RuII(bpy)3]2+, as a function of pump power (up to 2 TW/cm2)
      at 400 nm excitation. The transient absorption spectra in the 345-660 nm range up
      to 1 ns time delay enable the observation of the following photoproducts: the
      triplet 3MLCT (metal-to-ligand-charge-transfer) excited state, the reduced form
      [RuII(bpy)3]+, the oxidized species [RuIII(bpy)3]3+, and the solvated electron
      e(aq). The 3MLCT state is formed within the excitation pulse and undergoes
      vibrational relaxation in 3-5 ps, as evidenced by the shift of the ligand
      centered (LC) absorption band below 400 nm. Even at the highest pump powers, the
      majority of e(aq) originates from multiphoton ionization of [RuII(bpy)3]2+ and
      not from the solvent, generating [RuIII(bpy)3]3+ as a byproduct. At 10 ps time
      delay, the total concentration of the three product species is balanced by the
      depleted concentration of [RuII(bpy)3]2+, even at the highest fluences used,
      indicating that no further reaction products significantly contribute to the
      overall photochemistry. On the 100 ps time scale, most probably diffusion
      controlled reduction of ground-state [RuII(bpy)3]2+ by solvated electrons occurs,
      next to recombination between e(aq) and [RuIII(bpy)3]3+.

PMID- 17181315
TI  - Interaction of polar molecules with resonant radio frequency electric fields:
      imaging of the NO molecular beam splitting.
AB  - The interaction between a NO supersonic beam and a resonant radio frequency (RF)
      field is investigated using laser ionization coupled to imaging techniques. It is
      shown how the resonant interaction leads to a beam splitting of +/-0.2 degrees
      toward both positive and negative direction perpendicular to the beam propagation
      axis. This phenomenon is rationalized using a model based on molecular
      interferences produced by the action of the resonant RF electric field.

PMID- 17181316
TI  - Excited-state proton transfer from pyranine to acetate in gamma-cyclodextrin and
      hydroxypropyl gamma-cyclodextrin.
AB  - Excited-state proton transfer (ESPT) from pyranine (8-hydroxypyrene-1,3,6
      trisulfonate, HPTS) to acetate has been studied by picosecond and femtosecond
      emission spectroscopy in gamma-cyclodextrin (gamma-CD) and 2-hydroxypropyl-gamma
      cyclodextrin (HP-gamma-CD) cavities. In both the CDs, ESPT from HPTS to acetate
      is found to be very much slower (90 and 200 ps) than that in bulk water (0.15 and
      6 ps). From molecular modeling, it is shown that in the cyclodextrin cavity the
      acetate is separated from the OH group of HPTS by water bridges. As a result,
      proton transfer in the cavity requires rearrangement of the hydrogen-bond network
      involving the cyclodextrin. This is responsible for the marked slowdown of ESPT.
      ESPT of HPTS in substituted gamma-CD is found to be slower than that in the
      unsubstituted one. This is attributed to the hydroxypropyl groups, which prevent
      close approach of acetate to HPTS.

PMID- 17181317
TI  - Photophysics of an indigo derivative (keto and leuco structures) with singular
      properties.
AB  - Spectral and photophysical properties of the indigo derivative Cibalackrot in
      keto and reduced (leuco) forms were studied by absorption spectra, fluorescence
      and pulse radiolysis and compared with the structurally similar indigo. With the
      keto form of this dye, fluorescence (phiF = 0.76) and intersystem crossing (phiT
      = 0.11) are dominant, whereas with indigo, efficient internal conversion (phiIC =
      0.99) is observed, probably involving proton transfer through intramolecular
      hydrogen bonds. With Cibalackrot, this pathway is blocked, supporting the above
      model for indigo. With the reduced form of Cibalackrot, more than 98% of the
      absorbed quanta are dissipated through S1 approximately --> S0 internal
      conversion, which contrasts with leuco-indigo, where fluorescence (phiF = 0.35),
      internal conversion (phiIC = 0.53) and intersystem crossing (phiT = 0.125) are
      found to be competitive. In addition, a synthetic precursor of Cibalackrot
      (preCiba) was also investigated. This has a rigid molecular structure (with a
      moiety identical to Cibalackrot and the other to indigo), but intra- or
      intermolecular proton transfer is allowed between adjacent carbonyl and N-H
      groups. With this precursor in its keto structure the photophysical parameters
      are generally very close to those of the keto form of indigo, and different from
      those of Cibalackrot. A more detailed investigation of the time-decay profiles of
      preCiba in dioxane (and with added water and D2O) has shown that these follow
      biexponential laws with a shorter component of 14-25 ps, which appears associated
      with a risetime at longer wavelength emissions (and to a positive preexponential
      at shorter emission wavelengths) and a longer lived (decay) component of 104-130
      ps. In the steady-state spectra of preCiba, the variation with temperature
      reveals a blue shift of the emission maxima, which is interpreted as the presence
      (simultaneous emission) of two species (keto and enol) in the excited state.
      Indigo and deuterated indigo are also found to present a similar behavior. The
      overall data are interpreted as to be due to an excited-state process involving
      the proton transfer between keto and enol forms. Rate constants with values of 7
      x 10(10) s-1 for preCiba and 1.6 x 10(11) s-1 for deuterated indigo were
      obtained. This inverse isotope effect is justified on the basis of the proposed
      model for proton-transfer excited-state deactivation.

PMID- 17181319
TI  - Quenching of singlets and triplets by reversible ionization followed by charge
      recombination.
AB  - The reversible electron transfer from donor to excited molecule (acceptor of
      electron) is shown to be the irreversible energy quenching, if it is completed by
      subsequent irreversible recombination radical-ions which are produced. The Stern
      Volmer constant of fluorescence as well as the Markovian rate constant of triplet
      quenching are calculated analytically, assuming the electron transfer is contact.
      The multiple Rehm-Weller effect is shown to be peculiar to both constants.

PMID- 17181318
TI  - Photophysical properties of a 1,2,3,4,5,6-hexasubstituted fullerene derivative.
AB  - The photophysical properties of a novel 1,2,3,4,5,6-hexasubstituted fullerene
      derivative (1) are examined in this study. In addition to the ground state
      absorption spectrum of 1, we report its triplet-triplet absorption spectrum and
      molar extinction coefficient (Deltae(T-T)), as well as the triplet quantum yield
      (PhiT), lifetime (tauT), and energy (ET). The saturation of a single six-member
      ring on the fullerene cage results in significant changes in the triplet state
      properties as compared to that of pristine C60. The triplet-triplet absorption
      spectrum shows a hypsochromic shift in long wavelength absorption, and both the
      triplet state lifetime and the triplet quantum yield are decreased. The triplet
      energy was found to be similar to that of C60. In addition, the quantum yield
      (PHI(delta)) of singlet oxygen generated by 1 was calculated and is found to be
      significantly less than in the case of C60.

PMID- 17181321
TI  - Direct dynamics simulations of O(3P) + HCl at hyperthermal collision energies.
AB  - The dynamics of the O(3P) + HCl reaction at hyperthermal collision energies were
      investigated using the quasiclassical trajectory method. Stationary points on the
      OClH 3A" and 3A' potential energy surfaces (PESs) were also examined. The lowest
      transition state leading to OCl + H on the 3A" surface is 2.26 eV above the
      reagents at the CCSD(T)/cc-pVTZ level of theory. This saddle point is bent and
      product-like. Direct dynamics calculations at the MP2/cc-pVTZ level of theory
      were used to investigate the excitation functions for OH + Cl, OCl + H, and O + H
      + Cl formation. OCl is formed mainly from small-impact-parameter collisions, and
      the OCl + H excitation function peaks around 5 eV, where it is similar in
      magnitude to the OH + Cl excitation function. The shape of the OCl + H excitation
      function is discussed, and features are identified that should be general to
      hyperthermal collision dynamics.

PMID- 17181320
TI  - Photoinduced bimolecular electron transfer investigated by femtosecond time
      resolved infrared spectroscopy.
AB  - Ultrafast infrared transient absorption spectroscopy is used to study the
      photoinduced bimolecular electron transfer reaction between perylene in the first
      singlet excited state and 1,4-dicyanobenzene in acetonitrile and dichloromethane.
      Following vibrational marker modes on both donor and acceptor sides in real time
      provides direct insight into the structural dynamics during the reaction. A band
      narrowing on a time scale of a few tens of picoseconds observed on the
      antisymmetric CN stretching vibration of the dicyanobenzene radical anion
      indicates that a substantial part of the excess energy is channeled into
      vibrational modes of the product, despite the fact that the reaction is weakly
      exergonic. An additional narrowing of the same band on a time scale of several
      hundreds of picoseconds observed in acetonitrile only is interpreted as a
      signature of the dissociation of the geminate ion pairs into free ions.

PMID- 17181323
TI  - Optical and photophysical properties of indolocarbazole derivatives.
AB  - We present a study of the optical and photophysical properties of five ladder
      indolo[3,2-b]carbazoles, namely, M1, M2, M3, M4, and M5. The ground-state
      optimized structures were obtained by B3LYP/6-31G* density functional theory
      (DFT) calculations, whereas the optimization (relaxation) of the first singlet
      excited electronic state (S1) was performed using the restricted configuration
      interaction (singles) (RCIS/6-31G*) approach. The excitation to the S1 state does
      not cause important changes in the geometrical parameters of the compounds, as
      corroborated by the small Stokes shifts. The excitation and emission energies
      have been obtained by employing the time-dependent density functional theory
      (TDDFT). For all the compounds, excitation to the S1 state is weakly allowed,
      whereas the S2 <-- S0 electronic transition of each oligomer possesses a much
      larger oscillator strength. The absorption and fluorescence spectra of the
      compounds have been recorded in chloroform. A reasonable agreement is obtained
      between TDDFT vertical transition energies and the (0,0) absorption and
      fluorescence bands. On one hand, the pattern of the aliphatic side chains does
      not affect the absorption and fluorescence maxima of the compounds. On the other
      hand, the replacement of aliphatic chains by phenyl or thiophene rings induces
      hypsochromic shifts in the absorption and fluorescence spectra. Finally, the
      fluorescence quantum yield and lifetime of the compounds in chloroform have been
      obtained. From these data, the radiative and nonradiative rate constants of the
      deactivation of the S1 state have been determined.

PMID- 17181322
TI  - Electrolyte screening effect on the photoprotolytic cycle of excited photoacid in
      ice.
AB  - Time-resolved emission was used to measure the photoprotolytic cycle of an
      excited photoacid as a function of temperature, both in liquid water and in ice,
      in the presence of an inert salt. The inert salt affects the geminate
      recombination between the transferred proton with the conjugate base of the
      photoacid. We used the Debye-Huckel theory to express the screening of the
      Coulomb electrical potential by the inert salt. We find that in the liquid phase
      the measured screening effect is small and the Debye-Huckel expression slightly
      overestimates the experimental effect. In ice, the screening effect is rather
      large and the Debye-Huckel expression under estimates the measured effect. We
      explain the large screening in ice by the "salting-out" effect in ice that tends
      to concentrate the impurities to confined volumes to minimize the ice crystal
      energy.

PMID- 17181324
TI  - Vaporization thermodynamic studies by high-temperature mass spectrometry on some
      three-phase regions over the MnO-TeO2 binary line in the Mn-Te-O ternary system.
AB  - Knudsen effusion mass spectrometric measurements have been performed in the
      temperature range of 850-950 K over four three-phase mixtures, each phase mixture
      having at least one phase lying on the MnO-TeO2 binary line of the Mn-Te-O phase
      diagram, and the rest of the phases lying above this binary line. The three-phase
      mixtures investigated are Mn3O4 + MnO + Mn6Te5O16; Mn3O4 + Mn6Te5O16 + MnTeO3;
      Mn3O4 + Mn3TeO6 + MnTeO3; and Mn3TeO6 + MnTeO3 + Mn2Te3O8. The vapor pressures of
      the gaseous species TeO2, TeO, and Te2 over these three-phase mixtures were
      measured, and various heterogeneous solid-gas reactions were evaluated along with
      the homogeneous gas-phase reaction TeO2(g) + 0.5Te2(g) = 2 TeO(g). The enthalpy
      and Gibbs free energy of formation of the four ternary Mn-Te-O phases were
      deduced at T = 900 K. These values (in kJ.mol-1), along with the estimated
      uncertainties in them are Delta(f)H(o)m = 4150 +/- 19, 752 +/- 11, 1710 +/- 11,
      1924 +/- 40, and Delta(f)G(o)m= 2835 +/- 28, 511 +/- 11, 1254 +/- 19, 1238 +/-
      38, for Mn6Te5O16, MnTeO3, Mn3TeO6, and Mn2Te3O8, respectively. A thermochemical
      assessment was made to examine the conditions under which the ternary Mn-Te-O
      phases could be formed on a stainless steel clad of mixed-oxide-fueled (MO2; M =
      U + Pu) fast breeder nuclear reactors. The phase Mn3TeO6 could be formed when the
      fuel is even slightly hyperstoichiometric (O/M = 2.0002) and the phase Mn6Te5O16
      could also be formed when O/M = 2.0004. The threshold tellurium potential for the
      formation of Mn3TeO6 is higher than that for MnTe0.80 and CrTe1.10, but is
      comparable to that for MoTe1.10, and even lower than that for FeTe0.81 or
      NiTe0.63.

PMID- 17181325
TI  - Infrared vibrational autodetachment spectroscopy of microsolvated benzonitrile
      radical anions.
AB  - Vibrational spectra of microsolvated benzonitrile radical anions (C6H5CN- -S; S =
      H2O and CH3OH) were measured by probing the electron detachment efficiency in the
      3 microm region, representing resonance bands of autodetachment via OH stretching
      vibrations of the solvent molecules. The hydrogen-bonded OH band for both the
      cluster anions exhibited a large shift to the lower energy side with
      approximately 300 cm-1 compared to those for the corresponding neutral clusters.
      The solvent molecules are bound collinearly to the edge of the CN group of the
      benzonitrile anion in the cluster structures optimized with the density
      functional theory, in which the simulated vibrational energies are in good
      agreement with the observed band positions. Natural population analyses were
      performed for a qualitative implication in changes of solvent orientation upon
      electron attachment. Asymmetric band shapes depending on the vibrational modes
      are discussed with respect to dynamics of the autodetachment process from a
      theoretical aspect incorporated with density functional calculations.

PMID- 17181326
TI  - Cationic and anionic fragmentation of dichloromethane following inner-shell (Cl
      1s) photoexcitation.
AB  - The cationic and anionic fragmentation of dichloromethane (CH2Cl2) molecule have
      been investigated in the energy range of the Cl K shell by using synchrotron
      radiation, ion yield spectroscopy, and electron-ion coincidence spectroscopy.
      Total and partial ion-yield and mass spectra have been recorded as a function of
      the photon energy. We were able to identify several singly and multiply charged
      cationic fragments and the following anionic species: H-; C-; Cl-. The present
      results provide the first experimental report of negative ion formation from a
      molecule excited at the Cl 1s edge. In addition, our electron-ion coincidence
      data provide strong evidence of the preservation of molecular alignment for the
      photodissociation of CH2Cl2 after deep core-electron resonant excitation.

PMID- 17181327
TI  - Intracluster ion-molecule reactions of Ti+ with C2H5OH and CF3CH2OH clusters:
      influence of fluorine substituents on chemical reactivity.
AB  - A laser ablation-molecular beam/reflectron time-of-flight mass spectrometric
      technique was used to investigate the ion-molecule reactions that proceed within
      Ti+(ROH)n (R = C2H5, CF3CH2) heterocluster ions. The mass spectra exhibit a major
      sequence of cluster ions with the formula Ti+(OR)m(ROH)n (m = 1, 2), which is
      attributed to sequential insertions of Ti+ into the O-H bond of C2H5OH or
      CF3CH2OH molecules within the heteroclusters, followed by H eliminations. The
      TiO+ and TiOH+ ions produced from the reactions of Ti+ with C2H5OH are
      interpreted as arising from insertion of Ti+ into the C-O bond, followed by C2H5
      and C2H6 eliminations, respectively. When Ti+ reacted with CF3CH2OH, by contrast,
      considerable contributions from TiFOH+, TiF2+, and TiF2OH+ ions were observed in
      the mass spectrum of the reaction products, indicating that F and OH abstractions
      are the dominant product channels. Ab initio calculations of the complex of Ti+
      with 2,2,2-trifluoroethanol show that the minimum energy structure is that in
      which Ti+ is attached to the O atom and one of the three F atoms of 2,2,2
      trifluoroethanol, forming a five-membered ring. Isotope-labeling experiments
      additionally show that the chemical reactivity of heterocluster ions is greatly
      influenced by the presence of fluorine substituents and cluster size. The
      reaction energetics and formation mechanisms of the observed heterocluster ions
      are discussed.

PMID- 17181328
TI  - Dynamics of 9-hydroxyphenalenone studied by one-dimensional solid-state spin
      exchange NMR.
AB  - We present a new NMR method to clarify the dynamics of proton tautomerism in
      solid 9-hydroxyphenalenone. Two 13C resonance lines influenced by the proton
      tautomerism have a chemical-shift difference between them, which increases with
      decreasing temperature. To depict the precise potential curve of the proton
      tautomerism, the chemical-shift difference when the proton tautomerism is
      completely frozen is necessary. For solid 9-hydroxyphenalenone and its
      derivatives, the freezing temperatures are often under -100 degrees C. When the
      freezing temperatures are below the temperature range in which standard magic
      angle spinning NMR probes can perform a sample spinning, it is very difficult to
      obtain the shift difference. The NMR experiments based on this new method are
      performed at a temperature significantly higher than -100 degrees C at which the
      proton tautomerism is still active. The new method yields the 13C spin relaxation
      rates, the rates for the proton tautomerism, and the populations of the two
      tautomers. Using the populations and the 13C chemical-shift difference at that
      temperature, we determined the chemical-shift difference at the freezing
      temperature. We also obtained several parameters characterizing the potential
      profile for the proton dynamics in solid 9-hydroxyphenalenone.

PMID- 17181329
TI  - Infrared spectra and ab initio calculations for the F- -(CH4)n (n = 1-8) anion
      clusters.
AB  - Infrared spectra of mass-selected F- -(CH4)n (n = 1-8) clusters are recorded in
      the CH stretching region (2500-3100 cm-1). Spectra for the n = 1-3 clusters are
      interpreted with the aid of ab initio calculations at the MP2/6-311++G(2df 2p)
      level, which suggest that the CH4 ligands bind to F- by equivalent, linear
      hydrogen bonds. Anharmonic frequencies for CH4 and F--CH4 are determined using
      the vibrational self-consistent field method with second-order perturbation
      theory correction. The n = 1 complex is predicted to have a C3v structure with a
      single CH group hydrogen bonded to F-. Its spectrum exhibits a parallel band
      associated with a stretching vibration of the hydrogen-bonded CH group that is
      red-shifted by 380 cm-1 from the nu1 band of free CH4 and a perpendicular band
      associated with the asymmetric stretching motion of the nonbonded CH groups,
      slightly red-shifted from the nu3 band of free CH4. As n increases, additional
      vibrational bands appear as a result of Fermi resonances between the hydrogen
      bonded CH stretching vibrational mode and the 2nu4 overtone and nu2+nu4
      combination levels of the methane solvent molecules. For clusters with n < or =
      8, it appears that the CH4 molecules are accommodated in the first solvation
      shell, each being attached to the F- anion by equivalent hydrogen bonds.

PMID- 17181330
TI  - Raman spectral conformational order indicators in perdeuterated alkyl chain
      systems.
AB  - Conformational order indicators for perdeuterated alkyl chain systems are
      identified in the Raman spectra of nonadecane-d40, polyethylene-d4, and stearic
      acid-d35. Six spectral indicators are identified:
      I[nu(a)(CD2)2196]/I[nu(a)(CD2)2172], I[nu(C-C)G]/I[nu(C-C)T],
      I[nu(s)(CD3)]/I[nu(a)(CD2)2172], I[nu(s)(CD2)]/I[nu(a)(CD2)2172], and the full
      width at half-maximum (fwhm) and frequency of the nu(s)(CD2) mode. Among these
      indicators, the ratio of I[nu(a)(CD2)2196]/I[nu(a)(CD2)2172] is considered a
      primary indicator of conformational order, since it responds to alkyl chain
      conformational changes in a manner similar to the I[nu(a)(CH2)]/I[nu(s)(CH2)]
      primary indicator for hydrogenated systems. Other indicators are correlated to
      this primary indicator to derive a better understanding of the effect of
      structural attributes on conformational order in perdeuterated alkyl chain
      systems. These Raman spectral order indicators are applicable to any
      perdeuterated alkyl-containing system including lipids, biological membranes,
      alkylsilane-based chromatographic stationary phases, and self-assembled
      monolayers.

PMID- 17181331
TI  - Altering the emission behavior with the turn of a thiophene ring: the
      photophysics of condensed ring systems of alternating benzenes and thiophenes.
AB  - Six aromatic compounds with embedded thiophenes differing in the number of rings
      (2-5) and thiophene orientation along the long axis of the molecule (syn, anti)
      were investigated. Photophysical properties, steady-state absorption,
      fluorescence, phosphorescence, lifetimes, quantum yields, and a comprehensive
      time-resolved spectroscopic analysis (femtosecond and nanosecond transient
      absorption spectroscopy) have been studied as a function of molecular structure.

PMID- 17181332
TI  - Infrared spectra of the complexes of trifluoroethene with dimethyl ether,
      acetone, and oxirane: a cryosolution study.
AB  - Infrared spectra of solutions of trifluoroethene and dimethyl ether, acetone, or
      oxirane in liquid krypton and liquid argon have been studied. For each Lewis base
      the formation of a 1:1 complex with the Lewis acid was observed. The C-H
      stretching of trifluoroethene being perturbed by a strong Fermi resonance, the
      complexes with trifuloroethene-d were also investigated and showed that in each
      case the hydrogen bond between the acid and base is of the traditional, red
      shifting type. The structures of the complexes were investigated using ab initio
      calculations. These indicate that with dimethyl ether and acetone two different
      isomeres can be formed, but with a single one detected in the solution in each
      case. The Fermi resonance in the complex with unlabeled trifluoroethene is
      discussed using data derived form ab initio potential and dipole hypersurface
      calculations. The complexation enthalpies of the complexes were obtained from
      temperature dependent studies of the solutions and are discussed in relation to
      the ab initio complexation energies and Monte Carlo free energy perturbation
      calculations of solvent effects.

PMID- 17181333
TI  - Empirical determination of the harmonic force constants in benzene. 4. The Fermi
      resonances.
AB  - In this article, we present a continuation of our work on the refinement of the
      harmonic force constants Fi,k in benzene (in symmetrized Whiffen's coordinates)
      and on a growing number of higher order (anharmonic) force constants, Fi,j,k and
      Fi,j,k,l, that are of importance for the benzene isotopomer invariant potential
      energy surface. The refined set of harmonic and anharmonic force constants
      improves the agreement between the experimental levels and those calculated
      theoretically. The emphasis of the present work is on the analysis of the two
      notable Fermi resonances in benzene (nu8 +nnu1 <=> (n +1)nu1 + nu6, where n = 0,
      1, ... m, and nu20 <=> nu8 + nu19 <=> nu1 + nu6 + nu19). For this purpose, we
      have further extended our fully dimensional, fully symmetrized, and
      nonperturbative vibrational procedure to the vibrational structure of the benzene
      isotopic species with D6h symmetry.

PMID- 17181334
TI  - Furan-formic acid dimers: an ab initio and matrix isolation study.
AB  - The dimers formed by formic acid (FA) and furan are investigated by ab initio
      methods and matrix isolation spectroscopy. Nine complexes with binding energies
      between -3.91 and -0.82 kcal/mol (MP2/6-311++G(d,p) + ZPE + BSSE) are identified.
      Another five weaker bound complexes are localized at lower level of theory only.
      The binding in the furan-FA dimers can be described in terms of OH...O, C=O...H,
      HO...H, CH...O, OH...pi, and CH...pi interactions. Therefore, the furan-FA
      complexes are classified in two types: (1) the dimers where the OH hydrogen of
      formic acid interacts with the furan molecule and (2) the dimers where the main
      interactions of FA with the furan molecule are via the less acidic CH hydrogen.
      Duning's and Pople's triple and double basis sets were used to study the
      dependence of the geometries and energies of the complexes from the basis set.
      BSSE (basis set superposition error) counterpoise corrections (CP) were included
      during the geometry optimizations of all dimers at the MP2/6-31G(d,p) level of
      theory. Matrix isolation spectroscopy allowed us to record the IR spectrum of
      aggregates between FA and furan. By comparison of the experimental IR spectrum
      with calculated IR spectra of a variety of complexes, it was possible to identify
      the most stable furan-FA dimer as the major product of the aggregation.

PMID- 17181335
TI  - Matrix isolation and theoretical study of the reaction of substituted phosphines
      with CrCl2O2.
AB  - The reactions between CrO2Cl2 and a series of substituted phosphines have been
      investigated using matrix isolation infrared spectroscopy. For all of the
      phosphines except PF3, twin jet co-deposition of the two reagents into argon
      matrices at 14 K initially led to the formation of weak bands due to the
      corresponding phosphine oxide. For all of the phosphines, subsequent irradiation
      with light of lambda > 300 nm led to the growth of a number of intense new bands
      that have been assigned to the phosphine oxide complexed to CrCl2O, following an
      oxygen atom transfer reaction. Gas-phase, merged jet reactions prior to matrix
      deposition led to a significant yield of the uncomplexed phosphine oxide.
      Theoretical calculations at the B3LYP/6-311++g(d,2p) level were carried out in
      support of the experimental work, to support product band assignments and clarify
      the nature of the molecular complexes.

PMID- 17181336
TI  - Spectroscopic signatures of halogens in clathrate hydrate cages. 1. Bromine.
AB  - We report the first UV-vis spectroscopic study of bromine molecules confined in
      clathrate hydrate cages. Bromine in its natural hydrate occupies 51262 and 51263
      lattice cavities. Bromine also can be encapsulated into the larger 51264 cages of
      a type II hydrate formed mainly from tetrahydrofuran or dichloromethane and
      water. The visible spectra of the enclathrated halogen molecule retain the
      spectral envelope of the gas-phase spectra while shifting to the blue. In
      contrast, spectra of bromine in liquid water or amorphous ice are broadened and
      significantly more blue-shifted. The absorption bands shift by about 360 cm-1 for
      bromine in large 51264 cages of type II clathrate, by about 900 cm-1 for bromine
      in a combination of 51262 and 51263 cages of pure bromine hydrate, and by more
      than 1700 cm-1 for bromine in liquid water or amorphous ice. The dramatic shift
      and broadening in water and ice is due to the strong interaction of the water
      lone-pair orbitals with the halogen sigma* orbital. In the clathrate hydrates,
      the oxygen lone-pair orbitals are all involved in the hydrogen-bonded water
      lattice and are thus unavailable to interact with the halogen guest molecule. The
      blue shifts observed in the clathrate hydrate cages are related to the spatial
      constraints on the halogen excited states by the cage walls.

PMID- 17181337
TI  - Heterogeneous uptake of ozone on reactive components of mineral dust aerosol: an
      environmental aerosol reaction chamber study.
AB  - We have undertaken a kinetic study of heterogeneous ozone decomposition on alpha
      Fe2O3 (hematite) and alpha-Al2O3 (corundum) aerosols under ambient conditions of
      temperature, pressure, and relative humidity in order to better understand the
      role of mineral dust aerosol in ozone loss mechanisms in the atmosphere. The
      kinetic measurements are made in an environmental aerosol reaction chamber by use
      of infrared and ultraviolet spectroscopic probes. The apparent heterogeneous
      uptake coefficient, gamma, for ozone reaction with alpha-Fe2O3 and alpha-Al2O3
      surfaces is determined as a function of relative humidity (RH). The uptake of
      ozone by the iron oxide surface is approximately an order of magnitude larger
      than that by the aluminum oxide sample, under dry conditions. At the pressures
      used, alpha-Fe2O3 shows clear evidence for catalytic decomposition of ozone while
      alpha-Al2O3 appears to saturate at a finite ozone coverage. The measured uptake
      for both minerals decreases markedly as the RH is increased. Comparison with
      other literature reports and the atmospheric implications of these results are
      discussed.

PMID- 17181338
TI  - Competitive consecutive electron transfer in determination of ionization
      potentials: ketene derivatives.
AB  - Kinetics of competitive consecutive electron transfer was used to determine
      ionization potentials of transient species. Kinetics of two-stage electron
      transfer reactions in aprotic solvent was studied using 355 nm laser flash
      photolysis. The concentrations of transients produced by the laser flash
      photolysis were monitored by their light absorption. Triplet-excited tetrachloro
      p-benzo-quinone (p-chloranil) generated by a 355 nm laser flash oxidized diethyl
      ketene, diphenyl ketene, or phenyl ethyl ketene to form radical cations. The
      ketene radical cations, in turn, oxidized tertiary amine, forming ground state
      ketene and ammonium radical cation. The kinetics of the disappearance of ketene
      radical cations (and/or appearance of ammonium radical cations) due to
      consecutive, competitive electron transfer to ketene and p-chloranil radical
      cations was monitored. By monitoring kinetics in the presence of tertiary amines
      with different oxidation potentials, it was established that in acetonitrile the
      oxidation potential of diethyl ketene was 5.4 eV; for phenyl ethyl ketene, it was
      approximately 4.8 eV; and for diphenyl ketene, it was 4.6 eV. The results were in
      agreement with the oxidation potentials of ketenes computed using published data.

PMID- 17181340
TI  - Chain photoreduction of CCl3F in TiO2 suspensions: enhancement induced by O2.
AB  - Trichlorofluoromethane (CFC 11) was photoreduced in aqueous suspensions of TiO2
      particles containing HCO2- ions and air. Dissolved O2 inhibited the reaction
      during an induction period that preceded the rapid formation of chloride ions.
      Reaction rates were higher in systems containing O2 as compared to analogous
      reactions that occurred in anaerobic suspensions. High photonic efficiencies of
      Cl- formation (> or =15) were achieved using suspensions with pH > or = 5. As was
      the case for studies with air-free suspensions, reactions are best described
      using a photoinitiated chain mechanism that produced CHCl2F and Cl- during the
      propagation steps. The enhanced yields obtained in the presence of air are
      attributed to the removal by O2 of electrons trapped in the oxide, which are
      converted first into H2O2 and then into reducing radicals that participate in the
      chain process. Enhanced yields of Freon photoreduction were also observed during
      illumination of air-free suspensions containing hydrogen peroxide, which were
      interpreted using a similar mechanism.

PMID- 17181339
TI  - EPR studies of amine radical cations. Part 2. Thermal and photo-induced
      rearrangements of propargylamine and allylamine radical cations in low
      temperature freon matrices.
AB  - Matrix EPR studies and quantum chemical calculations have been used to
      characterize the consecutive H-atom shifts undergone by the nitrogen-centered
      parent radical cations of propargylamine (1b*+) and allylamine (5*+) on thermal
      or photoinduced activation. The radical cation rearrangements of these
      unsaturated parent amines occur initially by a 1,2 H-atom shift from C1 to C2
      with pi-bond formation at the positively charged nitrogen; this is followed by a
      consecutive reaction involving a second H-atom shift from C2 to C3. Thus,
      exposure to red light (lambda > 650 nm) converts 1b*+ to the vinyl-type distonic
      radical cation 2*+ which in turn is transformed on further photolysis with blue
      green light (lambda approximately 400-600 nm) to the allene-type heteroallylic
      radical cation 3*+. Calculations show that the energy ordering is 1b*+ > 2*+ >
      3*+, so that the consecutive H-atom shifts are driven by the formation of more
      stable isomers. Similarly, the parent radical cation of allylamine 5*+ undergoes
      a spontaneous 1,2-hydrogen atom shift from C1 to C2 at 77 K with a t1/2 of
      approximately 1 h to yield the distonic alkyl-type iminopropyl radical cation
      6*+; this thermal reaction is attributed largely to quantum tunneling, and the
      rate is enhanced on concomitant photobleaching with visible light. Subsequent
      exposure to UV light (lambda approximately 350-400 nm) converts 6*+ by a 2,3 H
      shift to the 1-aminopropene radical cation 7*+, which is confirmed to be the
      lowest-energy isomer derived from the ionization of either allylamine or
      cyclopropylamine. Although the parent radical cations of N, N-dimethylallylamine
      (9*+) and N-methylallylamine (11*+) are both stabilized by the electron-donating
      character of the methyl group(s), the photobleaching of 9*+ leads to the
      remarkable formation of the cyclic 1-methylpyrrolidine radical cation 10*+. The
      first step of this transformation now involves the migration of a hydrogen atom
      to C2 of the allyl group from one of the methyl groups (rather than from C1); the
      reaction is then completed by the cyclization of the generated MeN + (=CH2)
      CH2CH2CH2* distonic radical cation, possibly in a concerted overall process. In
      contrast to the ubiquitous H-atom transfer from carbon to nitrogen that occurs in
      the parent radical cations of saturated amines, the alternate rearrangements of
      either 1b*+ or 5*+ to an ammonium-type radical cation by a hypothetical H-atom
      shift from C1 to the ionized NH2 group are not observed. This is in line with
      calculations showing that the thermal barrier for this transformation is much
      higher (approximately 120 kJ mol-1) than those for the conversion of 1b*+ --> 2*+
      and 5*+--> 6*+ (approximately 40-60 kJ mol-1).

PMID- 17181341
TI  - Dynamics study of the OH + O3 atmospheric reaction with both reactants
      vibrationally excited.
AB  - The dynamics of the title five-atom atmospheric reaction is studied by the
      quasiclassical trajectory method for vibrational states of OH over the range 2 <
      or = v < or = 9 and initial vibrational energies of O3 between 9 and 21 kcal mol
      1 using a previously reported double many-body expansion potential energy surface
      for HO4(2A). The results show that the reaction is controlled by both capture-
      and barrier-type mechanisms, with the rate constants depending strongly on the
      reactants' internal energy content. Also suggested from the magnitude of the
      calculated rate coefficients is that the title processes may not be ignorable
      when studying the stratospheric ozone budget.

PMID- 17181342
TI  - Influence of reagent rotation on (H-, D2) and (D-, H2) collisions: a quantum
      mechanical study.
AB  - Time-independent quantum mechanical (TIQM) approach (helicity basis truncated at
      k = 2) has been used for computing differential and integral cross sections for
      the exchange reaction H- + D2 (v = 0, j = 0-4) --> HD + D- and D- + H2 (v = 0, j
      = 0-3) --> HD + H- in three dimensions on an accurate ab initio potential energy
      surface. It is shown that the j-weighted differential reaction cross section
      values are in good agreement with the experimental results reported by Zimmer and
      Linder at four different relative translational energies (Etrans = 0.55, 0.93,
      1.16 and 1.48 eV) for (H-, D2) and at one relative translational energy (Etrans =
      0.6 eV) by Haufler et al. for both (H-, D2) and (D-, H2) collisions. The j
      weighted integral reaction cross section values are in good agreement with the
      crossed beam measurements by Zimmer and Linder in the Etrans range 0.5-1.5 eV and
      close to the guided ion beam results by Haufler et al. for (H-, D2) in the range
      0.8-1.2 eV. Time-dependent quantum mechanical (TDQM) results obtained using
      centrifugal sudden approximation are reported in the form of integral reaction
      cross section values as a function of Etrans in the range 0.3-3.0 eV for both
      reactions in three dimensions on the same potential energy surface. The TDQM
      reaction cross section values decline more sharply than the TIQM results with
      increase in the initial rotational quantum number (j) for the D2 molecules in
      their ground vibrational state (v = 0) for (H-, D2) collisions. The computed j
      weighted reaction cross section values are in good agreement with the
      experimental results reported by Zimmer and Linder for (H-, D2) collisions and
      guided ion beam results by Haufler et al. for both (H-, D2) and (D-, H2)
      collisions for energies below the threshold for electron detachment channel.

PMID- 17181343
TI  - An all-atom force field for metallocenes.
AB  - A new all-atom force field, for the molecular modeling of metallocenes was
      constructed. Quantum chemical calculations were performed to obtain several force
      field terms not yet defined in the literature. The remainder were transferred
      from the OPLS-AA/AMBER framework. The parametrization work included the obtention
      of geometrical parameters, torsion energy profiles, and distributions of atomic
      charges that blend smoothly with the OPLS-AA specification for a variety of
      organic molecular fragments. Validation was carried out by comparing simulated
      and experimental data for five different ferrocene derivatives in the crystalline
      phase. The present model can be regarded as a step toward a general force field
      for metallocenes, built in a systematic way, easily integrated with OPLS-AA, and
      transferable between different metal-ligand combinations.

PMID- 17181344
TI  - Covalent interaction and semiempirical modeling of small molecules.
AB  - The use of sophisticated methods for modeling complex systems is gaining ever
      more importance recently because they allow the design of material with
      properties tailored to specific applications. However, problems may arise from
      conflicts between different reaction pathways inherent in the wide variety of
      chemical elements used. This is reflected by the impossibility of exactly solving
      the Schroedinger equation or of exactly describing the exchange interaction in
      density functional theory when the system complexity increases. An alternative is
      offered by the application of semiempirical methods because they strongly reduce
      system complexity. Normally, this is accomplished by increasing the degree of the
      approximations to the detriment of the formalism generality. This work is aimed
      to improve the semiempirical electronegativity equalization method. This is
      accomplished by modifying the point charge Madelung potential with the
      introduction of covalent interaction to better describe the chemical bonds.

PMID- 17181345
TI  - Diffusion-controlled reactions: hydrodynamic interaction between charged,
      uniformly reactive spherical reactants.
AB  - In this work, different models of hydrodynamic interaction (HI) are examined in
      the diffusion-controlled reaction between uniformly reactive charged spherical
      particles. In addition to Oseen "stick" and "slip" models of HI, one is
      considered that accounts for the disturbance of fluid flow by the ions around one
      reactive partner as they interact with a neighboring reactive species. This
      interaction is closely related to the "electrophoretic effect" in electrokinetics
      and can be described by a fairly simple electrophoretic, or E-tensor. These
      models are applied to the electron-transfer quenching reaction of Ru(bpy)3(2+)
      and methyl viologen (MV2+) over a wide range of NaCl concentrations (Chiorboli,
      C. et al., J. Phys. Chem. 1988, 92, 156). The back reaction is also considered.
      From a comparison of the salt dependence of the model and experimental rates, it
      is concluded that the "E-tensor" model works best and ignoring HI altogether
      works worst. The Oseen "stick" and "slip" models fall between these.

PMID- 17181346
TI  - Ionic association of hydroperoxide anion HO2- in the binding mean spherical
      approximation. Spectroscopic study of hydrogen peroxide in concentrated sodium
      hydroxide solutions.
AB  - The ultraviolet-visible (UV-vis) spectroscopy of hydrogen peroxide in
      concentrated sodium hydroxide solutions was studied. The peroxide band in the UV
      range shifts from approximately 214 nm to approximately 236 nm as the NaOH
      concentration increases from 0.338 mol dm-3 to 13.1 mol dm-3. The band originates
      from an intramolecular electronic transition of the hydroperoxide anion HO2-, as
      indicated by the negligible temperature effect on the band position and confirmed
      by ab initio quantum mechanical calculations. It is postulated that the
      bathochromic shift of the peroxide band that accompanies the increase in NaOH
      concentration originates from the formation of the ion pair (Na+HO2-). The
      equilibrium constant for the ion association reaction (0.048 mol-1 dm3) and the
      characteristics of the individual absorption bands of the hydroperoxide anion and
      its associate with Na+ were determined from the numerical modeling of the
      absorbance data, using the binding mean spherical approximation (BIMSA).

PMID- 17181347
TI  - On the spectroscopic and thermochemical properties of ClO, BrO, IO, and their
      anions.
AB  - A coupled cluster composite approach has been used to accurately determine the
      spectroscopic constants, bond dissociation energies, and heats of formation for
      the X1(2)II(3/2) states of the halogen oxides ClO, BrO, and IO, as well as their
      negative ions ClO-, BrO-, and IO-. After determining the frozen core, complete
      basis set (CBS) limit CCSD(T) values, corrections were added for core-valence
      correlation, relativistic effects (scalar and spin-orbit), the pseudopotential
      approximation (BrO and IO), iterative connected triple excitations (CCSDT), and
      iterative quadruples (CCSDTQ). The final ab initio equilibrium bond lengths and
      harmonic frequencies for ClO and BrO differ from their accurate experimental
      values by an average of just 0.0005 A and 0.8 cm-1, respectively. The bond length
      of IO is overestimated by 0.0047 A, presumably due to an underestimation of
      molecular spin-orbit coupling effects. Spectroscopic constants for the spin-orbit
      excited X2(2)III(1/2) states are also reported for each species. The predicted
      bond lengths and harmonic frequencies for the closed-shell anions are expected to
      be accurate to within about 0.001 A and 2 cm-1, respectively. The dissociation
      energies of the radicals have been determined by both direct calculation and
      through use of negative ion thermochemical cycles, which made use of a small
      amount of accurate experimental data. The resulting values of D0, 63.5, 55.8, and
      54.2 kcal/mol for ClO, BrO, and IO, respectively, are the most accurate ab initio
      values to date, and those for ClO and BrO differ from their experimental values
      by just 0.1 kcal/mol. These dissociation energies lead to heats of formation,
      DeltaH(f) (298 K), of 24.2 +/- 0.3, 29.6 +/- 0.4, and 29.9 +/- 0.6 kcal/mol for
      ClO, BrO, and IO, respectively. Also, the final calculated electron affinities
      are all within 0.2 kcal/mol of their experimental values. Improved
      pseudopotential parameters for the iodine atom are also reported, together with
      revised correlation consistent basis sets for this atom.

PMID- 17181348
TI  - Quantum mechanical size and steric hindrance.
AB  - A quantum mechanical definition of molecular size and shape is formulated from
      the electronic second moment of the Hartree-Fock wave function. The shape tensor
      is defined to be invariant with respect to the origin. The geometric average of
      the eigenvalues of the tensor correlates very well with van der Waals and Bragg
      Slater radii. There is also a close linear relationship between this definition
      of molecular size and molecular volumes determined computationally using
      isodensity contours. Furthermore, this definition of molecular size is effective
      in predicting the steric effects of substituents, as predicted by existing
      methods, such as the modified Taft Ee(s), P-values, and n-values.

PMID- 17181349
TI  - Isomer stability and bond-breaking energies of N8C8H8 cages.
AB  - Molecules consisting entirely or predominantly of nitrogen have been extensively
      investigated for their potential as high-energy density materials (HEDM). Such
      molecules react to produce N2 and large amounts of energy, but many such
      molecules are too unstable for practical applications. In the present study, cage
      isomers of N8C8H8 are studied using theoretical calculations to determine the
      structural features that lead to the most stable cages and determine the
      energetics of dissociation for the various isomers. The isomers are evaluated for
      thermodynamic (isomer vs isomer) stability and kinetic (with respect to
      dissociation) stability. Density functional theory (B3LYP), perturbation theory
      (MP2), and coupled-cluster theory [CCSD(T)] are employed, in conjunction with the
      cc-pVDZ basis set of Dunning. Trends in isomer stability and dissociation
      energies are calculated and discussed.

PMID- 17181350
TI  - Density functional study on geometrical features and electronic structures of di
      mu-oxo-bridged [Mn2O2(H2O)8]q+ with Mn(II), Mn(III), and Mn(IV).
AB  - We report the geometrical features and electronic structures of di-mu-oxo-bridged
      Mn-Mn binuclear complexes with H2O ligands [Mn2O2(H2O)8]q+ in the iso- and mixed
      valence oxidation states. All of the combinations among Mn(II), Mn(III), and
      Mn(IV) ions are considered the oxidation states of the Mn-Mn center, and the
      changes in molecular structure induced by the different electron configurations
      of Mn-based orbitals are investigated in relation to the oxygen-evolving complex
      (OEC) of photosystem II. The stable geometries of complexes are determined by
      using the hybrid-type density functional theory for both of the highest- and
      lowest-spin couplings between Mn sites, and the lowest-spin-coupled states are
      energetically more favorable than the highest-spin-coupled states except in the
      case of the complexes with the Mn(II) ion. The coordination positions of H2O
      ligands at the Mn(II) site tend to shift from the octahedral positions in
      contrast to those at the Mn(III) and Mn(IV) sites. The shape of the Mn2O2 core
      and the distances between the Mn ions and the H2O ligands vary depending on the
      electron occupations of the octahedral eg orbitals on the Mn site with an
      antibonding nature for the Mn-ligand interactions, indicating the trend as Mn(II)
      O > Mn(III)-O and Mn(IV)-O, O-Mn(II)-O > O-Mn(III)-O > O-Mn(IV)-O among the iso
      valence Mn2O2 cores, and O-Mn(lower)-O < O-Mn(higher)-O within the mixed-valence
      Mn2O2 core, and as Mn(II)-OH2 and Mn(III)-OH2 > Mn(IV)-OH2 for the axial H2O
      ligand. The optimized geometries of model complexes are compared with the X-ray
      structure of the OEC, and it is suggested that the cubane-like Mn cluster of the
      active site may not contain a Mn(II) ion. The effective exchange integrals are
      estimated by applying the approximate spin projection to clarify the magnetic
      coupling between Mn sites, and the superexchange pathways through the di-mu-oxo
      bridge are examined on the basis of the singly occupied magnetic orbitals derived
      from the singlet-coupled natural orbitals in the broken-symmetry state. The
      comparisons of the calculated results between [Mn2O2(H2O)8]q+ in this study and
      [Mn2O2(NH3)8]q+ reported by McGrady et al. suggest that the symmetric pathways
      are dominant to the exchange coupling constant, and the crossed pathway would be
      less important for the former than it would for the latter in the Mn(III)
      Mn(III), Mn(IV)-Mn(IV), and Mn(III)-Mn(IV) oxidation states.

PMID- 17181351
TI  - Dual-basis analytic gradients. 1. Self-consistent field theory.
AB  - Analytic gradients of dual-basis Hartree-Fock and density functional theory
      energies have been derived and implemented, which provide the opportunity for
      capturing large basis-set gradient effects at reduced cost. Suggested pairings
      for gradient calculations are 6-31G/6-31G**, dual[-f,-d]/cc-pVTZ, and 6-311G*/6
      311 + +G(3df,3pd). Equilibrium geometries are produced within 0.0005 A of large
      basis results for the latter two pairings. Though a single, iterative SCF
      response equation must be solved (unlike standard SCF gradients), it may be
      obtained in the smaller basis set, and integral screening further reduces the
      cost for well-chosen subsets. Total nuclear force calculations exhibit up to 75%
      savings, relative to large-basis calculations.

PMID- 17181352
TI  - Ab initio study of hydrogen-bond formation between cyclic ethers and selected
      amino acid side chains.
AB  - Binding energies for hydrogen-bonded complexes of six cyclic ethers with five
      hydrogen-bond donor molecules that mimic selected amino acid side chains have
      been calculated at the MP2/6-31G*, MP2/6-31+G*, MP2/6-311++G**(single point), and
      MP2/aug-cc-pvtz levels, using geometries obtained with or without counterpoise
      corrections throughout the geometry optimization. The calculated basis set
      superposition error (BSSE) amounts to 10-20% and 5-10% of the uncorrected binding
      energies for the neutral and ionic species, respectively, at the MP2/aug-cc-pvtz
      level. The authors conclude that the O...H distances in the hydrogen bonds and
      binding energies for the studied systems may be determined with uncertainties of
      up to 0.08 A and 1-2 kcal/mol, respectively, in comparison with the MP2/aug-cc
      pvtz values at a reasonable computational cost by performing standard geometry
      optimization at the MP2/6-31+G* level. Hydrogen-bond formation energies are more
      negative for cyclic ethers compared to their counterparts with a C=C double bond
      in the ring next to the oxygen atom. The less negative hydrogen-bonding energy
      and the increased O...H separation have been attributed to the reduced basicity
      of the ether oxygen when the lone pairs can enter conjugation with the pi
      electrons of the Calpha=Cbeta double bond. The present study is the first step
      toward the development of an affordable computational level for estimating the
      binding energies of natural product, fused ring ether systems to the human
      estrogen receptor.

PMID- 17181353
TI  - Quantum mechanical calculations of tryptophan and comparison with conformations
      in native proteins.
AB  - We report a detailed analysis of the potential energy surface of N-acetyl-l
      tryptophan-N-methylamide, (NATMA) both in the gas phase and in solution. The
      minima are identified using the density-functional-theory (DFT) with the 6-31g(d)
      basis set. The full potential energy surface in terms of torsional angles is
      spanned starting from various initial configurations. We were able to locate 77
      distinct L-minima. The calculated energy maps correspond to the intrinsic
      conformational propensities of the individual NATMA molecule. We show that these
      conformations are essentially similar to the conformations of tryptophan in
      native proteins. For this reason, we compare the results of DFT calculations in
      the gas and solution phases with native state conformations of tryptophan
      obtained from a protein library. In native proteins, tryptophan conformations
      have strong preferences for the beta sheet, right-handed helix, tight turn, and
      bridge structures. The conformations calculated by DFT, the solution-phase
      results in particular, for the single tryptophan residue are in agreement with
      native state values obtained from the Protein Data Bank.

PMID- 17181354
TI  - New findings on the Diels-Alder reactions. An analysis based on the bonding
      evolution theory.
AB  - Two Diels-Alder type reactions, i.e., normal electron demand (NED) between 1,3
      butadiene (BD) and acrolein (Acr) and inverse electron demand (IED) between 2,4
      pentadienal (PDA) and methyl vinyl ether (MVE), have been investigated using the
      bonding evolution theory (BET). BET combines topological analysis of the electron
      localization function (ELF) and catastrophe theory. Catalyst effect has been
      incorporated through Lewis acid BH3. The B3LYP hybrid HF/DFT method along with 6
      31G(d), 6-311++G(d,p) basis sets have been used. All reactions yield two-stage
      mechanism and there is no topological evidence that they might be concerted with
      two bonds partially formed during transition structure. A formation of six
      membered ring requires 10 (or 11) steps separated by two types of catastrophes:
      fold and cusp. The first "intermolecular" bond (C1-C6) is formed at 1.93, 1.92 A
      (NED) and 1.92, 1.97 A (IED). The six-membered ring is "closed" at 2.11, 2.13 A
      (NED) and 2.5, 2.6 A (IED) via formation of the second bond C4-C5. All reactions
      begin with "reduction" of C=C bonds to single C-C (cusp catastrophes).
      Subsequently, the nonbonding electron density is concentrated (fold catastrophes)
      on terminal C atoms. Finally the new bonds, C1-C6 and C4-C5, are established
      (cusp catastrophes). Both magnitude and regularity of the electron
      redistribution, happening during reactions enable us to distinguish two effects:
      (1) the "ring effect", where a large amount of electron density is regularly
      transferred from double C=C bonds to intermolecular regions and single C-C bonds,
      (2) the "side chain effect"--usually weaker and irregular--involving
      substituents' bonds. In the transition structure, well formed bonding basin
      V(C1,C6), is observed only for the PDA...BH3/MVE reaction. For other reactions
      only the nonbonding basins: V(C1) and V(C6), are found in the interaction region
      C1...C6.

PMID- 17181355
TI  - Computational study on the bond dissociation enthalpies in the enolic and ketonic
      forms of beta-diketones: their influence on metal-ligand bond enthalpies.
AB  - A computational study on the thermodynamic properties of 13 beta-diketones is
      presented. The B3LYP//6-311+G(2d,2p)//B3LYP/6-31G(d) theoretical approach was
      employed to compute the O-H and C-H bond dissociation enthalpies and enthalpy of
      tautomerization and to estimate standard gas-phase enthalpies of formation for
      the radicals and for the parent molecules. The gas-phase enthalpies of formation
      for the neutral molecules are in excellent agreement with available experimental
      data, supporting the estimates made for the radicals. The latter are very
      important for the clarification of the thermochemistry of many beta-diketonato
      metal complexes previously reported in the literature. Importantly, when
      substituents R = -CHR' are attached to the beta-diketone's scaffold, C-H
      homolytic bond cleavage is always favored with respect to O-H bond scission.

PMID- 17181356
TI  - Theoretical investigation of one-photon and two-photon absorption properties for
      multiply N-confused porphyrins.
AB  - We have theoretically investigated a series of multiply N-confused porphyrins and
      their Zn or Cu complexes for the first time by using DFT(B3LYP/6-31G*) and
      ZINDO/SOS methods. The electronic structure, one-photon absorption (OPA), and two
      photon absorption (TPA) properties have been studied in detail. The calculated
      results indicate that the OPA spectra of multiply N-confused porphyrins are red
      shifted and the OPA intensities decrease compared to normal porphyrin. The
      maximum two photon absorption wavelengths lambda(max) are blue-shifted and the
      TPA cross sections delta(max) are increased 22.7-112.1 GM when the N atoms one by
      one are inverted from core to beta position to form multiply N-confused
      porphyrins. Especially delta(max) of N3CP get to 164.7 GM. The electron donors 
      C6F5s at meso-position can make the TPA cross section delta(max) increase. After
      forming metal complexes with Cu or Zn, the TPA properties of multiply N-confused
      porphyrins are further increased except for N3CP, N4CP. Our theoretical findings
      demonstrate that the multiply N-confused prophyrins as well as their metal
      complexes and derivatives are promising molecules that can be assembled series of
      materials with large TPA cross section, and are sure to be the subject of further
      investigation.

PMID- 17181357
TI  - Ground and lowest-lying electronic states of CoN. A multiconfigurational study.
AB  - The lowest-lying X1Sigma+, a3Phi, b3II, c5Delta, A1Phi, and B1II electronic
      states of CoN have been investigated at the ab initio MRCI and MS-CASPT2 levels,
      with extended atomic basis sets and inclusion of scalar relativistic effects.
      Among the singlet states, the A1Phi and B1II states have been described for the
      first time. Potential energy curves, excitation energies, spectroscopic
      constants, and bonding character for all states are reported. Comparison with
      other early transition-metal nitrides (ScN, TiN, VN, and CrN), isoelectronic
      (NiC) and isovalent (RhN and IrN) species has been made, besides analyzing the
      B1II <=> X1+ electronic transition in terms of Franck-Condon factors, Einstein
      coefficients, and radiative lifetimes. At both levels of theory, the following
      energetic order has been obtained: X1Sigma+, a3Phi, b3II, c5Delta, A1Phi, and
      B1II, with good agreement with experimental results. In contrast, previous DFT
      and MRCI calculations predicted the ground state to be the 5Delta state.

PMID- 17181358
TI  - Is NO3 formed during the decomposition of nitramine explosives?
AB  - Quantum chemistry calculations reveal that it is both thermodynamically and
      kinetically feasible for NO2 to be oxidized by RDX (1,3,5-trinitrohexahydro-s
      triazine) or its initial decomposition products. Thus, NO3 (nitrate radical) may
      be produced during the thermal decomposition of RDX and other nitramines.
      However, experimental studies of the gaseous products, by mass spectrometry and
      microwave spectroscopy, have never detected NO3. This fact is reconciled with the
      calculations by noting that (1) the electron-impact, positive-ion mass spectrum
      of NO3 shows little parent ion, (2) NO3 lacks a permanent electric dipole moment
      and is therefore invisible to microwave spectroscopy, and (3) NO3 is quite
      reactive. Further experiments are encouraged and could lead to a new method for
      detecting concealed nitramines.

PMID- 17181359
TI  - Quantum chemical study of the structure and thermochemistry of the five-membered
      nitrogen-containing heterocycles and their anions and radicals.
AB  - The nitrogen-containing heterocycles are of interest as high-energy-density
      materials for use as propellants and explosives, while the pyrolysis of these
      compounds is also important in understanding the evolution of unwanted NO and NO2
      (NOx) from organic fuels such as coal and biomass. We have used ab initio and
      density functional methods to study the molecular structures and thermochemical
      properties of the five-membered nitrogen-containing heterocycles and their anions
      and radicals corresponding to respective heterolytic and homolytic loss of a
      hydrogen atom from either a nitrogen or carbon site. Many of these thermochemical
      properties have not previously been measured, especially for the heterocycles
      containing three and four nitrogen atoms. Using the theoretical methods CBS-APNO,
      G3, and G3B3, we calculate enthalpies of formation of 26.5, 42.4, 31.9, 63.7,
      46.8, 81.0, and 79.0 kcal mol-1 for pyrrole, pyrazole, imidazole, 1,2,3-triazole,
      1,2,4-triazole, 1H-tetrazole, and 2H-tetrazole. A correlation is developed
      between the number of nitrogen atoms in a heterocycle and its enthalpy, and we
      extrapolate this relationship to predict the enthalpy of formation of pentazole.
      N-H BDEs in the heterocycles typically increase with the number of nitrogen atoms
      in the molecule, while C-H BDEs are similar in all of the studied heterocycles,
      at around 120 kcal mol-1. In all cases the N-H BDEs are weaker than the C-H BDEs,
      suggesting abstraction of the N-H hydrogen atom is more likely. Deprotonation
      enthalpies and free energies reveal that the N-H protons become more acidic with
      increasing number of nitrogen atoms in the heterocycle. C-H protons are less
      acidic than N-H protons by ca. 49 kcal mol-1, or ca. 35 kcal mol-1 when adjacent
      to the NH group. Trends in N-H and C-H acidities can be qualitatively explained
      by electrostatic effects and electron affinities. From its use as a reference
      species in our calculations, we identify that the experimental enthalpy of
      pyrimidine (1,3-diazine) may be in error by ca. 1-3 kcal mol-1, and we recommend
      an enthalpy of formation of 44.8 +/- 1.0 kcal mol-1.

PMID- 17181360
TI  - Theoretical studies of symmetric five-membered heterocycle derivatives of
      carbazole and fluorene: precursors of conducting polymers.
AB  - Structures, electron ionization and excitation energies, and electron density
      distribution are studied for carbazole and fluorene derivatives substituted
      symmetrically by thiophene, ethylenodioxythiophene, furane, or pyrrole. The
      calculated properties of the molecules directly or indirectly mimic molecular
      parameters that are important for the design of processes of polymerization or
      for modeling the final polymer. The studies have been focused on the variation in
      the properties as a function of the chemical composition of the central fragment
      and the external rings. The calculated properties of consecutive oligomers
      indicate their fast convergence to values characterizing polymers.

PMID- 17181361
TI  - Sum-over-states calculation of the specific rotations of some substituted
      oxiranes, chloropropionitrile, ethane, and norbornenone.
AB  - A sum-over-states approach has been applied to the calculation of the specific
      rotations of several substituted oxiranes, 2-chloropropionitrile, and 30 degrees
      rotated ethane. In each case, the first few excited states proved to have only a
      relatively small effect on the calculated specific rotation. It was necessary to
      use a very large number of excited states in order to achieve convergence with
      the results of the more direct linear response method. However, the latter does
      not give information on which excited states are important in determining the
      specific rotation. Norbornenone is unique in that its greatly enhanced specific
      rotation as compared to norbornanone is associated with the low-energy n-pi*
      transition. The C=C bond orbitals interact with the C=O in the LUMO, and a
      density difference plot for going from the ground state to the first excited
      state clearly shows the perturbation of the C=C.

PMID- 17181362
TI  - Origin of the single chain magnet behavior of the Co(H2L)(H2O) compound with a 1D
      structure.
AB  - The paper is aimed at the elucidation of the main factors responsible for the
      single-chain magnet behavior of the cobalt(II) disphosphonate compound
      Co(H2L)(H2O) with a 1D structure. The model takes into account the spin-orbit
      interaction, the axial component of the octahedral crystal field acting on the
      ground-state cubic 4T1 terms of the Co(II) ions, the antiferromagnetic exchange
      interaction between Co(II) ions as well as the difference in the crystallographic
      positions of these ions. The conditions that favor the single-chain magnet
      behavior based on spin canting in a 1D chain containing inequivalent Co(II)
      centers are discussed. The peculiarities of this behavior in chains containing
      orbitally degenerate ions are revealed. The qualitative explanation of the
      experimental data is given.

PMID- 17181363
TI  - Ab initio exploration of rearrangement reactions: intramolecular hydrogen
      scrambling processes in acetone.
AB  - The recently developed metadynamics method is applied to the intramolecular
      hydrogen migration reactions of acetone in the gas phase. Comparison of different
      sets of collective coordinates allows efficient description of the underlying
      free energy surface. The simulations yielded numerous reactions: the enol-oxo
      tautomerism, the decomposition of acetone to various products, and rearrangement
      reactions. On the basis of the calculated activation barriers it is concluded
      that the enol-oxo tautomerism is the most frequent intramolecular proton-exchange
      process the acetone undergoes in the gas phase.

PMID- 17181364
TI  - Tunneling through weak interactions: comparison of through-space-, H-bond-, and
      through-bond-mediated tunneling.
AB  - Results from ab initio electronic structure theory calculations on model systems
      allow for the detailed comparison of tunneling through covalently bonded
      contacts, hydrogen bonds, and van der Waals contacts. Considerable geometrical
      sensitivity as well as an exponential distance dependence of the tunneling is
      observed for tunneling through various nonbonded contacts. However, the
      fundamental result from the present study is that at most a modest difference is
      observed between tunneling mediated by H-bonds and tunneling mediated by van der
      Waals contacts at typical distances for each type of interaction. These results
      are considered in relation to the pathways model of Beratan and Onuchic, and
      implications for understanding long-range tunneling in biological systems are
      discussed.

PMID- 17181365
TI  - Investigation on the correlation between the interaction energies of all
      substituted groups and the molecular stabilities of nitro compounds.
AB  - A model, similar to an isodesmic reaction, is for the first time presented in
      this paper for describing, defining, and calculating the interaction energies of
      the indirectly linked groups or atoms within one molecule. Its applications to
      nitro substitutes of methane, benzene, and cubane verify its validity for a
      separate group of closely related compounds by the reasonable correlation between
      the calculated interaction energies of all substituted groups and the molecular
      stabilities or experimental impact sensitivities. Comparing with some existing
      rules of assessing the molecular stability, this so-called interaction energy is
      calculated using a model considering the chemical structures, that is, the
      electronic environments of compounds, and can be well related with the
      stabilities of nitro compounds. All investigation results show that the so-called
      interaction energy is a new, quantitative, and useful tool to evaluate the
      stabilities of nitro compounds.

PMID- 17181366
TI  - Effect of adsorption site, size, and composition of Pt/Au bimetallic clusters on
      the CO frequency: a density functional theory study.
AB  - Density functional theory (DFT) calculations were performed to investigate the C
      O stretching frequency changes when a CO molecule was adsorbed to Pt/Au clusters
      of 2-4 atoms. Our calculations show that the adsorption site is the most
      sensitive quantity to the C-O stretching frequency shifts. All the bridge site
      adsorptions yield a CO frequency band of 1737-1927 cm-1 with the CO bond distance
      of 1.167-1.204 A regardless of cluster composition and size, and all the atop
      site adsorptions yield a CO frequency band of 2000-2091 cm-1 with the CO bond
      distance of 1.151-1.167 A. More detailed analysis of the two frequency bands
      shows that each band may consist of two emerging subbands with the lower
      frequencies corresponding to the CO adsorption to Pt atoms and the higher
      frequencies to the CO adsorption to Au atoms. The insensitivity of the CO
      frequency shift to the cluster size indicates that the trend discussed here for
      small clusters may be used to interpret the experimental observations for
      nanoparticles. Our results also illustrated that the Fourier transform infrared
      spectroscopy measurement may be used as a sensitive tool to identify adsorption
      sites of the Pt/Au nanoparticles using CO adsorption as the probe.

PMID- 17181367
TI  - Spatiotemporal dynamics of the Landolt reaction in an open spatial reactor with
      conical geometry.
AB  - In a previous study, the iodate-sulfite proton autoactivated reaction (Landolt
      reaction) was shown to exhibit spatial bistability and spatiotemporal
      oscillations when operated in an open spatial reactor with fixed "thickness",
      i.e., feed boundary to core distance. Here, we show that the spatial reactors
      with conical geometry enable one to rapidly probe the sensitivity of the above
      phenomena over a large range of the "thickness" parameter. This often-neglected
      parameter in chemical pattern studies plays an important role on the selection
      and stability of states. We reveal that the quenching capacity of slow diffusing
      polyacrylate ions on the spatiotemporal oscillations depends on this "thickness".
      The presented results should be useful for further research on reaction diffusion
      patterns and chemomechanical structures.

PMID- 17181368
TI  - Calorimetrically measurable enthalpic isotope effect.
AB  - Calorimetric techniques have revealed that the enthalpy of reaction with water is
      more exothermic by about 2.2 kcal/mol, for the perdeuteriated naphthalene anion
      radical (K+C10D8*-(s) + H2O(liq) --> 1/2C10D8H2(s) + 1/2C10D8(s) + KOH(aq)) than
      it is for the perprotiated system. These results, when coupled with the known
      enthalpy of electron transfer between naphthalene and its perdeuteriated analogue
      imply that the heat of hydrogenation of naphthalene decreases by about 1.8
      kcal/mol upon perdeuteriation of the naphthalene.

PMID- 17181372
TI  - New potential agents in treating diabetic kidney disease: the fourth act.
AB  - Despite the worldwide epidemic of chronic kidney disease complicating diabetes
      mellitus, current therapies directed against nephroprogression are limited to
      angiotensin conversion or receptor blockade. Nonetheless, additional therapeutic
      possibilities are slowly emerging. The diversity of therapies currently in
      development reflects the pathogenic complexity of diabetic nephropathy. The three
      most important candidate drugs currently in development include a
      glycosaminoglycan, a protein kinase C (PKC) inhibitor and an inhibitor of
      advanced glycation. In targeting primary mechanisms by which hyperglycaemia
      contributes to diabetic complications, these drugs could provide risk reduction
      complementary to the partial reduction proven for ACE inhibitors and angiotensin
      II receptor antagonists (angiotensin receptor blockers). Glycosaminoglycans act
      to restore glycoproteins present in reduced amounts in the glomerular basement
      membrane and mesangium of diabetic animal models. Components of the drug
      sulodexide prevent pathological changes and proteinuria in diabetic rats.
      Reductions in albuminuria, a hallmark of early diabetic kidney disease, have been
      reported in initial human trials. In the US, a multicentre phase II study has
      been completed, with an interim analysis indicating reduction in urinary albumin
      losses. Pivotal phase II trials have begun in patients with type 2 diabetes. A
      second metabolic pathway of diabetic complications is overexpression of PKC.
      Several activators of this family of intracellular kinases have been identified
      and PKC activation may result in tissue damage through a variety of mechanisms.
      In animal models, the inhibitor ruboxistaurin reduces albuminuria, diabetic
      histological changes and kidney injury. Like sulodexide, drug development of
      ruboxistaurin has reached completion of a phase II evaluation with mixed results.
      The third metabolic target is the nonenzymatic formulation of advanced glycation
      end-products (AGEs) through well described biochemical pathways. Multiple
      pathways lead to AGE accumulation in tissues in diabetes and diverse AGE products
      are formed. AGE deposition has been implicated in animal models of diabetic
      nephropathy. The leading AGE inhibitor currently in development is pyridoxamine,
      which has multiple actions that inhibit glycation. Pyridoxamine is an efficient
      AGE inhibitor in experimental diabetes. A phase II study in diabetic patients
      with nephropathy reported mixed efficacy results and a favourable safety profile.
      Phase III evaluation of pyridoxamine has not begun. These three classes of
      potential therapies, if successfully developed, will confirm that diabetic kidney
      disease has entered the era of biochemical treatments.

PMID- 17181374
TI  - Selecting the optimal oral antihistamine for patients with allergic rhinitis.
AB  - Allergic rhinitis (AR) is now recognised as a global health problem that affects
      10-30% of adults and up to 40% of children. Each year, millions of patients seek
      treatment from their healthcare provider. However, the prevalence of AR maybe
      significantly underestimated because of misdiagnosis, under diagnosis and failure
      of patients to seek medical attention. In addition to the classical symptoms such
      as sneezing, nasal pruritus, congestion and rhinorrhoea, it is now recognised
      that AR has a significant impact on quality of life (QOL). This condition can
      lead to sleep disturbance as a result of nasal congestion, which leads to
      significant impairment in daily activities such as work and school.
      Traditionally, AR has been subdivided into seasonal AR (SAR) or perennial AR
      (PAR). SAR symptoms usually appear during a specific season in which
      aeroallergens are present in the outdoor air such as tree and grass pollen in the
      spring and summer and weed pollens in the autumn (fall); and PAR symptoms are
      present year-round and are triggered by dust mite, animal dander, indoor molds
      and cockroaches. Oral histamine H(1)-receptor antagonists (H(1) antihistamines)
      are one of the most commonly prescribed medications for the treatment of AR.
      There are several oral H(1) antihistamines available and it is important to know
      the pharmacology, such as administration interval, onset of action, metabolism
      and conditions that require administration adjustments. When prescribing oral
      H(1) antihistamines, the healthcare provider must take into account the clinical
      efficacy and weigh this against the risk of adverse effects from the agent. In
      addition to the clinical efficacy, potential for improvement in QOL with a
      particular treatment should also be considered.

PMID- 17181373
TI  - Tuberculosis and HIV co-infection: a practical therapeutic approach.
AB  - HIV and tuberculosis (TB) are leading global causes of mortality and morbidity,
      and yet effective treatment exists for both conditions. Rifamycin-based
      antituberculosis therapy can cure HIV-related TB and, where available, the
      introduction of highly active antiretroviral therapy (HAART) has markedly reduced
      the incidence of AIDS and death. Optimal treatment regimens for HIV/TB co
      infection are not yet clearly defined. Combinations are limited by alterations in
      the activity of the hepatic cytochrome P450 (CYP) enzyme system, which in
      particular may produce subtherapeutic plasma concentrations of antiretroviral
      drugs. For example, protease inhibitors often must be avoided if the potent CYP
      inducer rifampicin is co-administered. However, an alternative rifamycin,
      rifabutin, which has similar efficacy to rifampicin, can be used with appropriate
      dose reduction. Available clinical data suggest that, for the majority of
      individuals, rifampicin-based regimens can be successfully combined with the non
      nucleoside reverse transcriptase inhibitors nevirapine and efavirenz. Most
      available HAART regimens in areas that have a high burden of TB contain one or
      the other of these drugs as a backbone. However, significant questions remain as
      to the optimal dose of either agent required to ensure therapeutic plasma
      concentrations, especially in relation to particular ethnic groups. The timing of
      HAART initiation after starting antituberculosis therapy continues to be
      controversial. Debate centres upon whether early initiation of HAART increases
      the risk of paradoxical reactions (immune reconstitution-related events) and
      other adverse events, or whether delay greatly elevates the risk of disease
      progression. Further prospective clinical data are needed to help inform practice
      in this area.

PMID- 17181375
TI  - Patient-controlled analgesia in the management of postoperative pain.
AB  - Patient-controlled analgesia (PCA) is a delivery system with which patients self
      administer predetermined doses of analgesic medication to relieve their pain.
      Since its introduction in the early 1980s, the daily management of postoperative
      pain has been extensively optimised. The use of PCA in hospitals has been
      increasing because of its proven advantages over conventional intramuscular
      injections. These include improved pain relief, greater patient satisfaction,
      less sedation and fewer postoperative complications. All PCA modes contain the
      following variables: initial loading dose, demand dose, lockout interval,
      background infusion rate and 1-hour or 4-hour limits. Morphine is the most
      studied and most commonly used intravenous drug for PCA. In spite of the fact
      that it is the 'first choice' for PCA, other opioids have been successfully used
      for this option. The most observed adverse effects of opioid-based PCA are nausea
      and vomiting, pruritus, respiratory depression, sedation, confusion and urinary
      retention. Although intravenous PCA is the most studied route of PCA, alternative
      routes have extensively been described in the literature. PCA by means of
      peridural catheters and peripheral nerve catheters are the most studied.
      Recently, transdermal PCA has been described. The use of peripheral or neuraxial
      nerve blocks is recommended to avoid the so called opioid tolerance observed with
      the intravenous administration of opioids. Numerous studies have shown the
      superiority of epidural PCA to intravenous PCA. The beneficial postoperative
      effects of epidural analgesia are more apparent for high-risk patients or those
      undergoing higher risk procedures. PCA with peripheral nerve catheters results in
      increased postoperative analgesia and satisfaction for surgery on upper and lower
      extremities. Serious complications occur rarely with these catheters. With the
      introduction of an Acute Pain Service, management of postoperative pain can be
      improved. This will also help to minimise adverse effects related to PCA and to
      avoid lethal mishaps.

PMID- 17181376
TI  - An overview of the diagnosis and treatment of erectile dysfunction.
AB  - Epidemiological studies have demonstrated an age-stratified increase in the
      incidence and prevalence of erectile dysfunction (ED). There is a greater degree
      of openness today when discussing sexual matters and more information on the
      treatment of ED is available to the public through the media. Quality-of-life
      issues are now a matter of great importance to the aging population. Men and
      their partners are no longer prepared to merely accept ED as a natural
      consequence of aging. The advent of a simple and effective oral therapy for ED
      has also indirectly fueled the increase in treatment-seeking behaviour among men.
      Despite great strides in research into ED, our knowledge and understanding of the
      pathophysiological mechanisms is still in its infancy. As a result, we are able
      to treat only the symptom of ED rather than prevent it. Common diseases found in
      the population, such as diabetes mellitus and coronary artery disease appear to
      be risk factors for the development of ED. Therefore, physicians need to identify
      any underlying co-existing organic diseases in their patients presenting with ED.
      Whenever possible, patients are encouraged to attend their consultation sessions
      with their partners because ED is a condition affecting 'the couple' and not just
      the man. Psychogenic aspects of ED should also be explored during the
      consultation. Efforts need to be made to uncover and address the presence of any
      psychological stressors, if necessary with the help of a psychosexual therapist.
      The first-line treatment of ED is oral phosphodiesterase-5 inhibitors. For those
      who do not respond to oral therapy, there is no defined 'step-ladder' escalation
      in alternative therapy. It is up to the physician to discuss the options with the
      patient or couple and reach a decision based on their preference.

PMID- 17181378
TI  - Recombinant full-length parathyroid hormone (1-84).
AB  - Full-length parathyroid hormone (PTH) 1-84 is a recombinant version of human PTH.
      It is approved in the EU for the treatment of postmenopausal women with
      osteoporosis who have a high risk of fractures. Once-daily subcutaneous
      administration of PTH(1-84) stimulates new bone formation and increases bone
      mass. In the pivotal, randomised, double-blind, multicentre, 18-month TOP trial
      in 2532 postmenopausal women with osteoporosis, subcutaneous PTH(1-84) 100
      microg/day significantly reduced the incidence of new or worsened vertebral
      fractures relative to placebo (primary endpoint). Moreover, the increase from
      baseline in bone mineral density (BMD) at the lumbar spine, total hip, femoral
      neck and trochanter was also significantly greater than in the placebo group. In
      another well designed study (PaTH; n = 238), 1 year of subcutaneous PTH(1-84) 100
      microg/day followed by 1 year of alendronate 10 mg/day resulted in significantly
      greater increases in total spine, femoral neck and total hip BMD at 24 months
      compared with patients who received placebo for the second year. During the first
      year, PTH(1-84) in combination with alendronate was no more effective than PTH(1
      84) monotherapy in terms of increasing areal lumbar spine BMD. PTH(1-84) is
      generally well tolerated, although patients should be monitored for elevated
      serum calcium.

PMID- 17181377
TI  - Shift work sleep disorder: burden of illness and approaches to management.
AB  - More than 6 million Americans work night shifts on a regular or rotating basis.
      The negative consequences of shift work have been established, and recent
      evidence suggests that patients with shift work sleep disorder (SWSD) are at
      increased risk of these consequences and co-morbidities. SWSD is a relatively
      common but under-recognised, and hence undertreated, condition with potentially
      serious medical, social, economic and quality-of-life consequences. In addition
      to increased risk of gastrointestinal and cardiovascular disease, patients with
      SWSD experience clinically significant excessive sleepiness or insomnia
      associated with work during normal sleep times, which has important safety
      implications. A number of studies have evaluated countermeasures or interventions
      in shift workers; proposed treatments include chronobiotic interventions, such as
      light exposure, melatonin, hypnotic agents, caffeine and CNS stimulants
      (amphetamine), and the wake-promoting agents modafinil and armodafinil. However,
      most studies evaluating pharmacological therapies and nonpharmacological
      interventions simulate night-shift work under conditions that may not accurately
      reflect real-world activities. Pharmacological and nonpharmacological
      countermeasures evaluated mostly in simulated laboratory conditions have been
      shown to improve alertness or sleep in shift workers but have not yet been
      evaluated in patients with SWSD. To date, three randomised, double-blind clinical
      studies have evaluated pharmacological therapies in patients with SWSD. These
      studies showed that modafinil and armodafinil significantly improve the ability
      to sustain wakefulness during waking activities (e.g. working, driving), overall
      clinical condition, and sustained attention or memory in patients with SWSD. In
      conclusion, SWSD is a common condition that remains under-recognised and
      undertreated. Further research is needed to evaluate different treatment
      approaches for this condition, to clarify the substantial health and economic
      consequences of SWSD, and to determine the potential for interventions or
      treatments to reduce the negative consequences of this condition.

PMID- 17181383
TI  - Fentanyl buccal tablet: in breakthrough pain in opioid-tolerant patients with
      cancer.
AB  - The fentanyl buccal tablet (FBT) is a new formulation of fentanyl that uses an
      effervescent drug delivery system to enhance penetration across the buccal mucosa
      for the treatment of breakthrough pain in opioid-tolerant patients with cancer.
      Fentanyl is rapidly absorbed from FBT across the buccal mucosa and into the
      bloodstream. Fentanyl is more rapidly absorbed and bioavailability is higher from
      FBT than from the oral transmucosal fentanyl citrate formulation. In a well
      designed phase III trial in opioid-tolerant patients with cancer, a single dose
      of FBT 100-800 microg provided clinically significant improvements in pain
      intensity from 15 to 60 minutes after the dose. Single FBT doses of 100-800
      microg were generally well tolerated; the majority of adverse events were mild to
      moderate in nature and typical of those associated with opioids.

PMID- 17181387
TI  - Setting the stage: early child and family characteristics as predictors of later
      loneliness in children with developmental disabilities.
AB  - Children with developmental disabilities often report having few friends.
      Researchers have tended to focus on social skill deficits, neglecting other
      potent predictors of children's feelings of loneliness. In a sample of 82
      children with developmental disabilities, we examined characteristics of the
      child at age 3 (i.e., the conclusion of early intervention services) as well as
      family income and emotional climate as predictors of children's reported feelings
      of loneliness at school during middle childhood (age 10). Children with lower
      levels of externalizing behavior problems at age 3 and from families with a more
      positive family climate, as indicated by the Family Environment Scale, reported
      less loneliness at age 10. Implications for children, families, and early
      intervention services are discussed.

PMID- 17181386
TI  - Famciclovir: a review of its use in herpes zoster and genital and orolabial
      herpes.
AB  - Famciclovir (Famvir) is the oral prodrug of penciclovir, an agent that has
      demonstrated antiviral activity against herpes simplex viruses, type 1 (HSV-1)
      and 2 (HSV-2) [which cause orolabial and/or genital herpes simplex], and against
      varicella zoster virus (VZV) [a reactivation of which leads to herpes zoster].
      Famciclovir has efficacy similar to that of aciclovir (in immunocompetent or
      immunocompromised patients) or valaciclovir (in immunocompetent patients) in the
      treatment of herpes zoster, and efficacy similar to aciclovir in the treatment of
      first or recurrent episodes of genital herpes (in immunocompetent or
      immunocompromised patients). Famciclovir also has efficacy in the suppression of
      recurrent episodes of genital herpes, and in the treatment of orolabial herpes,
      in immunocompetent patients. As such, famciclovir is a well tolerated first-line
      option for the treatment of herpes zoster and the treatment and suppression of
      genital herpes, and is approved for the treatment of recurrent orolabial herpes.
      Convenient patient-initiated single-day (for recurrent genital herpes) and single
      dose (for orolabial herpes) dosage regimens may contribute to treatment
      compliance, patient acceptability and subsequent treatment outcomes.

PMID- 17181388
TI  - Expressive language during conversational speech in boys with fragile X syndrome.
AB  - We compared the expressive syntax and vocabulary skills of 35 boys with fragile X
      syndrome and 27 younger typically developing boys who were at similar nonverbal
      mental levels. During a conversational speech sample, the boys with fragile X
      syndrome used shorter, less complex utterances and produced fewer different words
      than did the typically developing boys after controlling for their nonverbal MA,
      speech intelligibility, and mother's education. The boys with fragile X used less
      complex noun phrases, verb phrases, and sentence structure, but did not use fewer
      questions and negations. These findings suggest that the language difficulties in
      boys with fragile X reflect an overall expressive language delay and not a
      specific syntactic or vocabulary delay.

PMID- 17181389
TI  - Short form of the developmental behaviour checklist.
AB  - A 24-item short form of the 96-item Developmental Behaviour Checklist was
      developed to provide a brief measure of Total Behaviour Problem Score for
      research purposes. The short form Developmental Behaviour Checklist (DBC-P24) was
      chosen for low bias and high precision from among 100 randomly selected item
      sets. The DBC-P24 was developed from epidemiological data in the first three
      waves of the Australian Child to Adult Development study, and cross validated for
      groups with autism, fragile X, Prader-Willi, and Williams in this longitudinal
      study and in cross sectional Dutch, English, and Finnish samples of young people
      with intellectual disability. The DBC-P24 has low bias and high precision in
      cross-validation samples and achieves high sensitivity and specificity to full
      DBC-P based caseness decisions.

PMID- 17181390
TI  - Effect of "missing" information on fast mapping by individuals with vocabulary
      limitations associated with intellectual disability.
AB  - One phenomenon of language development is a dramatic increase in vocabulary size,
      driven by rapid word learning. For individuals with intellectual disabilities,
      the size of the lexicon often lags behind what would be expected both for CA and
      MA. I examined how well individuals with severely limited receptive vocabulary
      associated with intellectual disability retained a new word-picture map after a
      single exposure under conditions of varying difficulty. This study was a direct
      replication of a previous investigation with typically developing preschool
      children, enabling a direct comparison. Individuals with intellectual
      disabilities performed equally as well as control children in the initial
      exposure phase but poorer when asked to remember the initial map in the presence
      of other novel distracters or labels.

PMID- 17181391
TI  - Conjunctive visual search in individuals with and without mental retardation.
AB  - A comprehensive understanding of the basic visual and cognitive abilities of
      individuals with mental retardation is critical for understanding the basis of
      mental retardation and for the design of remediation programs. We assessed visual
      search abilities in individuals with mild mental retardation and in MA- and CA
      matched comparison groups. Our goal was to determine the effect of decreasing
      target-distracter disparities on visual search efficiency. Results showed that
      search rates for the group with mental retardation and the MA-matched comparisons
      were more negatively affected by decreasing disparities than were those of the CA
      matched group. The group with mental retardation and the MA-matched group
      performed similarly on all tasks. Implications for theory and application are
      discussed.

PMID- 17181392
TI  - Dynamical origins of stereotypy: relation of postural movements during sitting to
      stereotyped movements during body-rocking.
AB  - The relation between the movement dynamic properties of sitting still and of
      seated body-rocking in adults with stereotyped movement disorder and mental
      retardation and a contrast group of typically developing age-matched adults was
      examined. Continuous measurement of sequential displacements in center-of
      pressure was made using a force platform while subjects were engaged in seated
      body-rocking and quiet sitting. Properties of movement were compared across
      conditions (rocking, sitting) and groups (stereotyped movement disorder,
      contrast). The contrast group had the same modal frequency for both movement
      properties. The intrinsic dynamics of the stereotyped movement disorder group
      were similar to those of the contrast group for body-rocking but very different
      for quiet sitting. Findings support the suggestion that body-rocking in
      stereotyped movement disorder originates partly as an adaptation to an inability
      to control posture in a seated position.

PMID- 17181394
TI  - Different responsiveness of alveolar and tibial bone to bone loss stimuli.
AB  - Mandibular and systemic bone loss are poorly associated. We compared the effect
      of isocaloric protein undernutrition and/or ovariectomy on BMD and microstructure
      of mandibular alveolar and proximal tibia sites in adult rats. Mandibular bone
      was significantly less affected. INTRODUCTION: Whether mandibular bone and axial
      or peripheral skeleton respond similarly to systemic bone loss remains a subject
      of controversy. We have previously shown that mechanical loading during
      mastication influences bone mass and architecture of the mandibular alveolar
      bone. Isocaloric protein undernutrition and ovariectomy are known to cause bone
      loss and deterioration of bone microarchitecture at various axial and peripheral
      skeletal sites. We studied how the mandible, which is subjected to heavy, abrupt,
      and intermittent forces during mastication, responds to low-protein intake and/or
      ovariectomy and compared this response to that of the proximal tibia in adult
      rats. MATERIALS AND METHODS: Forty-four 6-month-old female Sprague-Dawley rats
      underwent transabdominal ovariectomy (OVX; n=22) or sham operation (n=22) and
      were pair-fed isocaloric diets containing either 15% or 2.5% casein (sham 15%,
      n=11; sham 2.5%, n=11; OVX 15%, n=11; and OVX 2.5%, n=11) for 16 weeks. BMD and
      bone microarchitecture parameters (e.g., bone volume fraction [BV/TV] and
      trabecular thickness and number) of the mandible and the proximal tibia were
      measured at the end of the experiment using DXA and microCT. RESULTS: Mandibular
      alveolar bone was negatively influenced by both protein undernutrition and OVX,
      but to a significantly lesser extent than the proximal tibia. In sham-operated
      animals, low-protein intake led to a 17.3% reduction of BV/TV in the mandible and
      84.6% in the tibia (p<0.001). In normal protein diet-fed animals, OVX led to a
      reduction of BV/TV of 4.9% in the mandible but 82% in the tibia (p<0.001). In the
      mandible, protein undernutrition resulted in thinner trabeculae (p<0.05), whereas
      OVX led to a reduction of trabecular number (p<0.05). CONCLUSIONS: Mandibular
      alveolar bone was found to be less sensitive to either protein undernutrition or
      OVX than the proximal tibia spongiosa. We hypothesize that the mechanical loading
      of the alveolar process during mastication may protect the alveolar bone from the
      detrimental effects observed in other skeletal sites, such as the proximal tibia.
      Morphological and embryological differences between the two skeletal sites might
      also play a role.

PMID- 17181395
TI  - Alterations of cortical and trabecular architecture are associated with fractures
      in postmenopausal women, partially independent of decreased BMD measured by DXA:
      the OFELY study.
AB  - We assessed the role of low aBMD and impaired architecture-assessed by an HR-pQCT
      system-in a case-control study of postmenopausal women with fractures. Vertebral
      and nonvertebral fractures are associated with low volumetric BMD and
      architectural alterations of trabecular and cortical bone, independent of aBMD
      assessed by DXA. INTRODUCTION: Alterations of bone architecture and low BMD both
      contribute to skeletal fragility, but the contribution of cortical and trabecular
      architecture, independently of areal BMD (aBMD), to the risk of fracture in
      postmenopausal women has not been thoroughly evaluated. We assessed the role of
      impaired architecture and low BMD in postmenopausal women with fractures.
      MATERIALS AND METHODS: A matched case-control study in women from the OFELY
      cohort was performed after 13 years of follow-up. One hundred one women (mean,
      73.7+/-8 years) who sustained a fragility fracture during the follow-up of the
      study were age-matched with one control who never had a fracture. Density and
      architecture at the distal radius and tibia were measured with high-resolution
      pQCT (HR-pQCT) using an XTreme CT (Scanco Medical AG, Bassersdorf, Switzerland).
      aBMD at the total hip and ultradistal radius was measured by DXA. RESULTS: There
      were 80 peripheral fractures in 72 women, 44 vertebral fractures in 34 women, and
      both types of fractures in 5 women over the 14 years of follow-up. At the distal
      radius, women with fractures had lower volumetric total (D tot) and trabecular (D
      trab) BMDs, BV/TV, cortical thickness (Cort Th), trabecular number (TbN), and
      trabecular thickness (TbTh) and higher trabecular separation (TbSp) and
      distribution of trabecular separation (TbSpSd) than controls without fractures.
      In a logistic model, each SD decrease of volumetric total and trabecular
      densities was associated with a significantly increased risk of fracture at both
      sites (ORs ranged from 2.00 to 2.47). After adjusting for aBMD measured by DXA at
      the ultradistal radius, differences between cases and controls remained
      significant for D trab, and there was a similar trend for TbN, TbSp, and TbSpSd,
      with adjusted ORs ranging from 1.32 to 1.50. At the distal tibia, before and
      after adjusting for total hip aBMD, differences between cases and controls
      remained significant for D tot, D trab, Cort Th, and TbTh, with adjusted ORs
      ranging from 1.80 to 2.09. CONCLUSIONS: In postmenopausal women, vertebral and
      nonvertebral fractures are associated with low volumetric BMD and architectural
      alterations of trabecular and cortical bone that can be assessed noninvasively
      and that are partially independent of aBMD assessed by DXA.

PMID- 17181396
TI  - Exercise and calcium combined results in a greater osteogenic effect than either
      factor alone: a blinded randomized placebo-controlled trial in boys.
AB  - We examined the combined effects of exercise and calcium on BMC accrual in pre-
      and early-pubertal boys. Exercise and calcium together resulted in a 2% greater
      increase in femur BMC than either factor alone and a 3% greater increase in BMC
      at the tibia-fibula compared with the placebo group. Increasing dietary calcium
      seems to be important for optimizing the osteogenic effects of exercise.
      INTRODUCTION: Understanding the relationship between exercise and calcium during
      growth is important given that the greatest benefits derived from these factors
      are achieved during the first two decades of life. We conducted a blinded
      randomized-controlled exercise-calcium intervention in pre- and early-pubertal
      boys to test the following hypotheses. (1) At the loaded sites (femur and tibia
      fibula), exercise and calcium will produce greater skeletal benefits than either
      exercise or calcium alone. (2) At nonloaded sites (humerus and radius-ulna),
      there will be an effect of calcium supplementation. MATERIALS AND METHODS: Eighty
      eight pre- and early-pubertal boys were randomly assigned to one of four study
      groups: moderate impact exercise with or without calcium (Ca) (Ex+Ca and
      Ex+placebo, respectively) or low impact exercise with or without Ca (No-Ex+Ca and
      No-Ex+Placebo, respectively). The intervention involved 20 minutes of either
      moderate- or low-impact exercise performed three times a week and/or the addition
      of Ca-fortified foods using milk minerals (392+/-29 mg/day) or nonfortified foods
      over 8.5 months. Analysis of covariance was used to determine the main and
      combined effects of exercise and calcium on BMC after adjusting for baseline BMC.
      RESULTS: At baseline, no differences were reported between the groups for height,
      weight, BMC, or bone length. The increase in femur BMC in the Ex+Ca group was
      approximately 2% greater than the increase in the Ex+placebo, No-Ex+Ca, or No
      Ex+Placebo groups (all p<0.03). At the tibia-fibula, the increase in BMC in the
      Ex+Ca group was approximately 3% greater than the No-Ex+placebo group (p<0.02)
      and 2% greater than the Ex+Placebo and the No-Ex+Ca groups (not significant). No
      effect of any group was detected at the humerus, ulna-radius, or lumbar spine for
      BMC, height, bone area, or volume. CONCLUSIONS: In this group of normally active
      boys with adequate calcium intakes, additional exercise and calcium
      supplementation resulted in a 2-3% greater increase in BMC than controls at the
      loaded sites. These findings strengthen the evidence base for public health
      campaigns to address both exercise and dietary changes in children for optimizing
      the attainment of peak BMC.

PMID- 17181397
TI  - Delayed development of Paget's disease in offspring inheriting SQSTM1 mutations.
AB  - Familial Paget's disease is associated with mutations in SQSTM1. We compared the
      age at diagnosis and severity of Paget's disease in parents with SQSTM1 mutations
      to their offspring who inherited a mutation. At any given age, the offspring were
      less likely to be diagnosed with Paget's disease and had less severe disease than
      their parents. INTRODUCTION: Mutations in sequestosome 1 (SQSTM1) occur in 25-50%
      of cases of familial Paget's disease and are thought to be disease-causing. We
      sought to determine whether there are differences in age at diagnosis and
      severity of disease in parents and their offspring who share the same genetic
      predisposition to Paget's disease. MATERIALS AND METHODS: Eighty-four offspring
      from 10 families (29 index patients with Paget's disease) with mutations in
      SQSTM1 were approached, and 58 agreed to participate. The ubiquitin-binding
      domain region of SQSTM1 was sequenced, and the presence or absence of the known
      mutation was established. The presence of Paget's disease in offspring who had
      inherited an SQSTM1 mutation was determined by bone scintigraphy and measurement
      of serum alkaline phosphatase (ALP). RESULTS: Twenty-three of 58 offspring had
      inherited a germline mutation in SQSTM1. The mean ALP was 77 U/liter in offspring
      with mutations and 72 U/liter in those without mutations (p=0.84). Scintiscans
      from four offspring (mean age, 45 years; mean ALP, 139 U/liter; mean skeletal
      involvement, 6%) showed evidence of Paget's disease but were normal in the other
      19 (mean age, 44 years; mean ALP, 64 U/liter). In comparison, in the 15 parents
      of the 23 offspring, the mean age of diagnosis was 48 years, the mean ALP was 850
      U/liter, and the mean skeletal involvement was 30%. There was a 63% reduction in
      the risk of being diagnosed with Paget's disease at a comparable age in the
      offspring compared with the parents (p=0.028). CONCLUSIONS: Only 17% of offspring
      inheriting an SQSTM1 mutation had evidence of Paget's disease on scintigraphy,
      and this was diagnosed at a later age and was less extensive than in their
      affected parents. SQSTM1 thus shows incomplete penetrance. The data are
      consistent with the hypothesis that an environmental factor is important in the
      pathogenesis and clinical phenotype of familial Paget's disease and that exposure
      to this factor may be falling.

PMID- 17181398
TI  - Enhanced bone regeneration associated with decreased apoptosis in mice with
      partial HIF-1alpha deficiency.
AB  - HIF-1alpha activates genes under hypoxia and was hypothesized to regulate bone
      regeneration. Surprisingly, HIF-1alpha+/- fracture calluses are larger, stronger,
      and stiffer than HIF-1alpha+/+ calluses because of decreased apoptosis. These
      data identify apoptosis inhibition as a means to enhance bone regeneration.
      INTRODUCTION: Bone regeneration subsequent to fracture involves the synergistic
      activation of multiple signaling pathways. Localized hypoxia after fracture
      activates hypoxia-inducible factor 1alpha (HIF-1alpha), leading to increased
      expression of HIF-1 target genes. We therefore hypothesized that HIF-1alpha is a
      key regulator of bone regeneration. MATERIALS AND METHODS: Fixed femoral
      fractures were generated in mice with partial HIF-1alpha deficiency (HIF-1alpha+/
      ) and wildtype littermates (HIF-1alpha+/+). Fracture calluses and intact
      contralateral femurs from postfracture days (PFDs) 21 and 28 (N=5-10) were
      subjected to microCT evaluation and four-point bending to assess morphometric and
      mechanical properties. Molecular analyses were carried out on PFD 7, 10, and 14
      samples (N=3) to determine differential gene expression at both mRNA and protein
      levels. Finally, TUNEL staining was performed on PFD 14 samples (N=2) to
      elucidate differential apoptosis. RESULTS: Surprisingly, fracture calluses from
      HIF-1alpha+/- mice exhibited greater mineralization and were larger, stronger,
      and stiffer. Microarray analyses focused on hypoxia-induced genes revealed
      differential expression (between genotypes) of several genes associated with the
      apoptotic pathway. Real-time PCR confirmed these results, showing higher
      expression of proapoptotic protein phosphatase 2a (PP2A) and lower expression of
      anti-apoptotic B-cell leukemia/lymphoma 2 (BCL2) in HIF-1alpha+/+ calluses.
      Subsequent TUNEL staining showed that HIF-1alpha+/+ calluses contained larger
      numbers of TUNEL+ chondrocytes and osteoblasts than HIF-1alpha+/- calluses.
      CONCLUSIONS: We conclude that partial HIF-1alpha deficiency results in decreased
      chondrocytic and osteoblastic apoptosis, thereby allowing the development of
      larger, stiffer calluses and enhancing bone regeneration. Furthermore, apoptosis
      inhibition may be a promising target for developing new treatments to accelerate
      bone regeneration.

PMID- 17181399
TI  - Negative regulation by p70 S6 kinase of FGF-2-stimulated VEGF release through
      stress-activated protein kinase/c-Jun N-terminal kinase in osteoblasts.
AB  - To clarify the mechanism of VEGF release in osteoblasts, we studied whether p70
      S6 kinase is involved in basic FGF-2-stimulated VEGF release in osteoblast-like
      MC3T3-E1 cells. In this study, we show that p70 S6 kinase activated by FGF-2
      negatively regulates VEGF release through SAPK/JNK in osteoblasts. INTRODUCTION:
      Vascular endothelial growth factor (VEGF) plays an important role in bone
      metabolism. We have previously reported that fibroblast growth factor-2 (FGF-2)
      stimulates the release of VEGF through p44/p42 mitogen-activated protein (MAP)
      kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in
      osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively
      regulates VEGF release. However, the mechanism behind VEGF release in osteoblasts
      is not precisely known. MATERIALS AND METHODS: The levels of VEGF released from
      MC3T3-E1 cells were measured by enzyme immunoassay. The phosphorylation of each
      protein kinase was analyzed by Western blotting. To knock down p70 S6 kinase in
      MC3T3-E1 cells, the cells were transfected with siRNA to target p70 S6 kinase.
      RESULTS: FGF-2 time-dependently induced the phosphorylation of p70 S6 kinase.
      Rapamycin significantly enhanced the FGF-2-stimulated VEGF release and VEGF mRNA
      expression. The FGF-2-induced phosphorylation of p70 S6 kinase was suppressed by
      rapamycin. Rapamycin markedly enhanced the FGF-2-induced phosphorylation of
      SAPK/JNK without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP
      kinase. SP600125, a specific inhibitor of SAPK/JNK, suppressed the amplification
      by rapamycin of the FGF-2-stimulated VEGF release similar to the levels of FGF-2
      with SP600125. Finally, downregulation of p70 S6 kinase by siRNA significantly
      enhanced the FGF-2-stimulated VEGF release and phosphorylation of SAPK/JNK.
      CONCLUSIONS: These results strongly suggest that p70 S6 kinase limits FGF-2
      stimulated VEGF release through self-regulation of SAPK/JNK, composing a negative
      feedback loop, in osteoblasts.

PMID- 17181400
TI  - Is a school-based physical activity intervention effective for increasing tibial
      bone strength in boys and girls?
AB  - This 16-month randomized, controlled school-based study compared change in tibial
      bone strength between 281 boys and girls participating in a daily program of
      physical activity (Action Schools! BC) and 129 same-sex controls. The simple,
      pragmatic intervention increased distal tibia bone strength in prepubertal boys;
      it had no effect in early pubertal boys or pre or early pubertal girls.
      INTRODUCTION: Numerous school-based exercise interventions have proven effective
      for enhancing BMC, but none have used pQCT to evaluate the effects of increased
      loading on bone strength during growth. Thus, our aim was to determine whether a
      daily program of physical activity, Action Schools! BC (AS! BC) would improve
      tibial bone strength in boys and girls who were pre- (Tanner stage 1) or early
      pubertal (Tanner stage 2 or 3) at baseline. MATERIALS AND METHODS: Ten schools
      were randomized to intervention (INT, 7 schools) or control (CON, 3 schools). The
      bone-loading component of AS! BC included a daily jumping program (Bounce at the
      Bell) plus 15 minutes/day of classroom physical activity in addition to regular
      physical education. We used pQCT to compare 16-month change in bone strength
      index (BSI, mg2/mm4) at the distal tibia (8% site) and polar strength strain
      index (SSIp, mm3) at the tibial midshaft (50% site) in 281 boys and girls
      participating in AS! BC and 129 same-sex controls. We used a linear mixed effects
      model to analyze our data. RESULTS: Children were 10.2+/-0.6 years at baseline.
      Intervention boys tended to have a greater increase in BSI (+774.6 mg2/mm4; 95%
      CI: 672.7, 876.4) than CON boys (+650.9 mg2/mm4; 95% CI: 496.4, 805.4), but the
      difference was only significant in prepubertal boys (p=0.03 for group x maturity
      interaction). Intervention boys also tended to have a greater increase in SSIp
      (+198.6 mm3; 95% CI: 182.9, 214.3) than CON boys (+177.1 mm3; 95% CI: 153.5,
      200.7). Change in BSI and SSIp was similar between CON and INT girls.
      CONCLUSIONS: Our findings suggest that a simple, pragmatic program of daily
      activity enhances bone strength at the distal tibia in prepubertal boys. The
      precise exercise prescription needed to elicit a similar response in more mature
      boys or in girls might be best addressed in a dose-response trial.

PMID- 17181401
TI  - Quantitative trait loci for BMD and bone strength in an intercross between
      domestic and wildtype chickens.
AB  - With chicken used as a model species, we used QTL analysis to examine the genetic
      contribution to bone traits. We report the identification of four QTLs for
      femoral traits: one for bone strength, one for endosteal circumference, and two
      affecting mineral density of noncortical bone. INTRODUCTION: BMD is a highly
      heritable phenotype, governed by elements at numerous loci. In studies examining
      the genetic contribution to bone traits, many loci have been identified in humans
      and in other species. The goal of this study was to identify quantitative trait
      loci (QTLs) controlling BMD and bone strength in an intercross between wildtype
      and domestic chickens. MATERIALS AND METHODS: A set of 164 markers, covering 30
      chromosomes (chr.), were used to genotype 337 F2-individuals from an intercross
      of domesticated white Leghorn and wildtype red junglefowl chicken. DXA and pQCT
      were used to measure BMD and bone structure. Three-point bending tests and
      torsional strength tests were performed to determine the biomechanical strength
      of the bone. QTLs were mapped using forward selection for loci with significant
      marginal effects. RESULTS: Four QTLs for femoral bone traits were identified in
      QTL analysis with body weight included as a covariate. A QTL on chr. 1 affected
      female noncortical BMD (LOD 4.6) and is syntenic to human 12q21-12q23. Also
      located on chr. 1, a locus with synteny to human 12q13-14 affected endosteal
      circumference (LOD 4.6). On chr. 2, a QTL corresponding to human 5p13-p15, 7p12,
      18q12, 18q21, and 9q22-9q31 affected BMD in females; noncortical (LOD 4.0) and
      metaphyseal (LOD 7.0) BMD by pQCT and BMD by DXA (LOD 5.9). A QTL located on chr.
      20 (LOD 5.2) affected bone biomechanical strength and had sex-dependent effects.
      In addition to the significant QTLs, 10 further loci with suggestive linkage to
      bone traits were identified. CONCLUSIONS: Four QTLs were identified: two for
      noncortical BMD, one for endosteal circumference, and one affecting bone
      biomechanical strength. The future identification of genes responsible for these
      QTLs will increase the understanding of vertebrate skeletal biology.

PMID- 17181402
TI  - Osteoporosis-related kyphosis and impairments in pulmonary function: a systematic
      review.
AB  - We conducted a systematic review to examine the relationship between osteoporotic
      vertebral fractures, kyphosis, and pulmonary function. Findings suggest modest
      but predictable declines in vital capacity related to the degree of kyphosis.
      However, there were only four studies, and all had significant methodologic
      limitations. Further high-quality research is needed. INTRODUCTION: Our objective
      was to systematically review the extent to which osteoporosis-related vertebral
      fractures and kyphosis affect pulmonary function. MATERIALS AND METHODS: We used
      a literature search from 1966 to 2006 (using Medline, EMBASE, and hand searches
      of references) for studies examining pulmonary function in patients without known
      lung disease who had vertebral fractures or kyphosis secondary to osteoporosis.
      Two reviewers independently abstracted data. Heterogeneity precluded formal meta
      analysis. RESULTS: Initial searches yielded 453 articles. After applying
      eligibility criteria, only four case-control studies of limited quality (e.g.,
      only one study was blinded) remained. Since 1966, only 109 patients (6 men) have
      been studied. All four studies reported reductions in vital capacity (VC), with
      values ranging from 68% to 94% of predicted values. This was quantified as a 9%
      reduction in predicted VC per vertebral fracture in one study. The degree of
      kyphosis clinically (one study) or radiographically (three studies) correlated
      with declines in VC; impairments were most notable at kyphotic angles>55 degrees.
      Statistically significant differences in percent predicted VC were obtained only
      when arm span or recalled height, rather than measured height, was used (two
      studies). CONCLUSIONS: Despite conventional teaching, the evidence relating
      osteoporotic vertebral fractures or kyphosis to pulmonary function is limited. On
      the basis of available studies, declines in VC secondary to kyphosis seem modest
      and directly related to the number of vertebral fractures or degree of kyphosis.
      Future studies need longitudinal follow-up of larger numbers of men and women,
      appropriate proxies for height, standardized measures for pulmonary function and
      kyphosis, and efforts to blind outcomes ascertainment.

PMID- 17181403
TI  - Describing the methicillin-resistant Staphylococcus aureus epidemic: a public
      health challenge.

PMID- 17181404
TI  - Structured treatment interruptions in chronic HIV management: where next?

PMID- 17181406
TI  - The Caribbean and Latin America: HIV prevalence.

PMID- 17181407
TI  - Filoviruses: recent advances and future challenges.

PMID- 17181408
TI  - Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis.
AB  - Faropenem medoxomil is the first oral penem in a new class of beta-lactam
      antibiotics. Faropenem medoxomil has excellent in vitro activity against
      Streptococcus pneumoniae, Haemophilus influenzae and other key pathogens
      implicated in acute bacterial rhinosinusitis. Clinical studies have demonstrated
      that, in the treatment of acute bacterial rhinosinusitis in adults, 7 days of
      treatment with faropenem medoxomil is as clinically and bacteriologically
      effective as 10 days of treatment with cefuroxime axetil. One study showed
      faropenem medoxomil to be superior to cefuroxime axetil. Overall, the safety
      profile of faropenem medoxomil is similar to that of most comparators.
      Specifically, the minimal impact of faropenem medoxomil on the gastrointestinal
      flora leads to less diarrhea and other adverse events than coamoxicillin
      clavulanate. Faropenem medoxomil has almost no drug-drug interactions and little
      requirement for dosage adjustments in the typical acute rhinosinusitis
      population.

PMID- 17181409
TI  - Ramoplanin: a topical lipoglycodepsipeptide antibacterial agent.
AB  - Ramoplanin, a novel antibiotic with activity against aerobic and anaerobic gram
      positive bacteria, acts to prevent cell wall peptidoglycan formation by binding
      to a key intermediate moiety, lipid II. It has been fast-tracked by the US FDA
      for the prevention of enterococcal infections and the treatment of Clostridium
      difficile. The minimum inhibitory concentration(90s) have been < or = 1.0
      microg/ml against gram-positive organisms examined. In carriers of vancomycin
      resistant enterococci, a double-blind, placebo-controlled Phase II trial of two
      doses of ramoplanin versus placebo showed proof of concept. A second Phase II
      trial also demonstrated the equivalence of ramoplanin compared with vancomycin
      for the treatment of C. difficile colitis. The clinical value and place in
      therapy of ramoplanin is dependent upon the results of Phase III trials
      addressing its utility in suppressing carriage of target organisms in the
      gastrointestinal tract or in the nares.

PMID- 17181410
TI  - Use of linezolid in children: an overview of recent advances.
AB  - Linezolid is the first member of a new generation of antibiotics, the synthetic
      oxazolidinones, to become available, with a broad spectrum of in vitro activity
      against gram-positive organisms, including methicillin-resistant Staphylococcus
      aureus, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E.
      faecium. Linezolid is showing great promise currently for the treatment of
      multiresistant gram-positive bacterial infections, especially complicated skin
      infections, catheter-induced bacteremia or nosocomial pneumonia both in the
      community and in a hospital setting, in children and in adults. Although most
      recent reports are favorable and anticipatory of a more extensive use of
      linezolid in appropriately selected pediatric population groups in the near
      future, following treatment failure of conventional antimicrobial agents, more
      clinical trials are, however, required to investigate the safety profile and
      tolerability of this new antibiotic in the pediatric population.

PMID- 17181411
TI  - First demonstration of the effectiveness of inhibitors of cellular protein
      kinases in antiviral therapy.
AB  - Viral replication and pathogenesis involves many cellular protein kinases, and
      many specific inhibitors of such kinase have been developed for the treatment of
      noninfectious diseases. As expected, such drugs have been repeatedly demonstrated
      to inhibit viral replication in cultured cells. Cellular protein kinases have
      thus been considered for several years as potentially valid targets for antiviral
      therapy. However, until recently there was no proof of such activity in vivo. The
      three papers discussed herein demonstrate that inhibitors of cellular protein
      kinases are indeed effective for the treatment of virus-induced disease in animal
      models and human clinical trials.

PMID- 17181412
TI  - Prophylactic antibiotics in obstetrics-gynecology: a current asset, a future
      liability?
AB  - Currently, prophylactic antibiotics have proven effective in lowering the
      postoperative and postprocedure infection rate following vaginal hysterectomy,
      emergency cesarean section for the patient in labor, radical hysterectomy,
      abdominal hysterectomy, pregnancy termination, hysterosalpingogram and
      intrauterine device insertion. Guidelines for the most effective and safe use are
      presented. Concerns are raised regarding the widespread prolonged use of
      prophylactic antibiotics on women in labor to prevent Group B streptococcal
      infections in newborn children and women with prolonged preterm membrane rupture.
      There is also an awareness needed of a growing incidence of infections seen in
      the hospital from community-acquired methicillin-resistant Staphylococcus aureus
      and Clostridium difficile. These problems have not been addressed by the current
      prophylactic antibiotic strategies.

PMID- 17181413
TI  - Didanosine, lamivudine-emtricitabine and efavirenz as initial therapy in naive
      patients.
AB  - There are currently several suitable and different antiretroviral regimens to
      start highly active antiretroviral therapy (HAART), and many clinicians and
      patients prefer once-daily therapy. The efficacy and potency of efavirenz (EFV)
      has been established in many clinical trials and cohort studies; its
      pharmacokinetics, allowing for a convenient once-daily administration, make EFV
      one of the first agents to be included in once-daily regimens in naive patients.
      The two nucleoside reverse transcriptase inhibitors (NRTIs) accompanying the
      third drug have become the central skeleton, or the 'backbone' of the therapeutic
      scheme. Among the different NRTI pairs, a didanosine-lamivudine (3TC) or
      emtricitabine backbone for combination antiretroviral therapy may be a good
      option compared with any current NRTI-combinations due to its security, tolerance
      and once-daily dose. In this article, we review the advantages and drawbacks of
      didanosine-XTC-EFV as the initial regimen of HAART in HIV-infected patients.

PMID- 17181414
TI  - Clinical implications of macrolide resistance in community-acquired respiratory
      tract infections.
AB  - Laboratory surveillance data suggest that macrolide resistance among
      Streptococcus pneumoniae has increased dramatically over the past 15 years. This
      review examines the specifics of macrolide resistance and the clinical relevance
      of in vitro susceptibility testing in light of the pharmacokinetics and
      pharmacodynamics of azithromycin and clarithromycin. These drugs concentrate
      extensively within respiratory tissue and have other positive characteristics not
      reflected by in vitro susceptibility testing. In general, clarithromycin is the
      most potent macrolide and the one most likely to maintain clinical efficacy
      against the low-level resistance associated with most macrolide-resistant
      pneumococci in the USA. These findings suggest that susceptibility data may
      underestimate clinical utility and that clarithromycin still has a place in the
      empiric treatment of respiratory infections.

PMID- 17181415
TI  - Evaluation and management of patients with pulmonary nontuberculous mycobacterial
      infections.
AB  - Nontuberculous mycobacteria (NTM) are emerging pathogens increasingly associated
      with chronic pulmonary disease. NTM are environmental saprophytes found in soil,
      dust and water and, unlike Mycobacterium tuberculosis, NTM are not transmitted
      from person to person. Pulmonary disease caused by NTM is a particular problem in
      older people without underlying immune compromise. The diagnosis of NTM pulmonary
      disease usually requires either multiple respiratory cultures that grow NTM or
      heavy growth of NTM from a single bronchoscopy or lung-biopsy specimen. High
      resolution computed tomography is the most useful radiographic study for
      diagnosis and to determine the extent of disease. Treatment includes multiple
      medications with activity against the particular NTM species, as single-drug
      therapy is likely to select for resistant organisms. Data demonstrating the
      effectiveness of specific drug regimens for NTM pulmonary disease are limited.
      Clarithromycin and azithromycin form the backbone of most treatment regimens
      because these drugs are active against many NTM species. Drug tolerability and
      cost are the major barriers to successful treatment of NTM pulmonary disease.
      Adjunctive therapies, including mucus clearance techniques and appetite
      stimulants, are unproven but may be of value in management of NTM pulmonary
      disease. Multicenter, randomized trials of macrolide-based therapies are sorely
      needed to determine the safest and most effective treatments for NTM pulmonary
      disease.

PMID- 17181416
TI  - Current clinical management of Legionnaires' disease.
AB  - Legionella pneumophila is increasingly recognized as a cause of both sporadic and
      epidemic community-acquired pneumonia. Clinical manifestations of Legionnaires'
      disease are not specific and current diagnostic scores are of limited use.
      Urinary antigen detection is an effective test for rapid diagnosis of infection
      caused by L. pneumophila serogroup 1. Improved outcomes regarding the time to
      defervescence, development of complications and length of stay, have been
      recently observed for patients treated with levofloxacin monotherapy. Current
      case-fatality rates for hospitalized patients with community-acquired Legionella
      pneumonia are lower than those traditionally reported for this infection.
      Effective preventive strategies are needed.

PMID- 17181417
TI  - Advances in the antiviral therapy of herpes virus infection in children.
AB  - Herpes viruses are ubiquitous and primary infections, with many of these viruses
      common during childhood. In general, children tolerate primary infection well,
      with only mild symptoms, but in the immunocompromised, including the newborn,
      infection can be associated with serious morbidity and mortality. Drug treatment
      for many of the herpes infections is available but is often associated with
      serious side effects. In the pediatric age group, treatment is further hindered
      by a lack of information on suitable dosing regimes, unavailability of oral
      solutions and a lack of clinical trials specifically investigating response to
      treatment in this group of patients. This article will review current evidence
      regarding the pharmacokinetics and dosing of the most commonly used antiherpetic
      agents and will look specifically at the treatment of the more common herpes
      virus infections in children.

PMID- 17181418
TI  - Current and future trends in the prevention, treatment and control of rabies.
AB  - Rabies remains a global zoonosis of major public health, agricultural and
      economic significance. Dogs are the major animal reservoirs in developing
      regions, wildlife maintain cycles of infection even in developed countries and
      new viral etiological agents continue to emerge. Nearly all human rabies cases
      are related directly to animal bite and thus, primary disease prevention requires
      minimization of suspected exposures. Once exposure occurs, modern prophylaxis
      entails immediate wound care, local infiltration of rabies immune globulin and
      parenteral administration of modern cell culture vaccines in multiple doses. Pre
      exposure vaccination should occur in selected population groups at risk of
      occupational exposure. Historically, survival from fatal rabies by at least five
      human patients, vaccinated prior to the onset of clinical signs, signaled initial
      optimism as to the theoretical utility of medical intervention. Recently, the
      heroic recovery of an unvaccinated teenager from clinical rabies offers hope of
      future specific therapy. Canine rabies elimination is the key towards ultimate
      reduction of the disease burden, as first illustrated in developed countries.
      Implementation of oral vaccination in free-ranging carnivore hosts demonstrates
      the feasibility of disease abatement in particular wildlife populations, such as
      demonstrated in Europe and North America, with an enhanced need for application
      to developing countries in the Americas, Africa and Eurasia.

PMID- 17181419
TI  - Recent advances in the understanding of infectious mononucleosis: are prospects
      improved for treatment or control?
AB  - Symptomatic primary Epstein-Barr virus infection is known more commonly as
      infectious mononucleosis, an illness known for afflicting adolescents and younger
      adults as a febrile illness accompanied by pharyngitis and lymphadenopathy.
      Historically believed to be generally benign, infectious mononucleosis has been
      linked more recently to increased risks of developing Hodgkin's lymphoma and
      multiple sclerosis. Advances in the understanding of host immune responses to
      Epstein-Barr virus have begun to elucidate the reasons why younger children
      typically experience subclinical infection whereas older individuals develop
      infectious mononucleosis. This review will highlight recent advances in the
      understanding of primary Epstein-Barr virus infection, and whether prospective
      treatments or vaccine strategies may affect native infection and its sequelae.

PMID- 17181420
TI  - Advances in the diagnosis and management of neurocysticercosis.
AB  - Neurocysticercosis is the most common cause of late-onset epilepsy in developing
      countries. The larval stage of Taenia solium is the causative agent of the
      disease. Recent advances in neuroimaging and serologic diagnostic techniques have
      led to increased recognition of its importance, but its pathogenesis is just
      beginning to be clarified. Experts now agree that the clinical manifestations,
      pathogenic mechanisms and optimal treatment vary with the number of parasites,
      their location and the degree of host inflammation. Symptomatic therapy (i.e.,
      antiepileptic medications and, when indicated, surgery) is critically important
      but there are also important roles for antiparasitic and anti-inflammatory drugs.
      Neurocysticercosis is a potentially eradicable disease but this is probably
      unlikely to be achieved in the short term.

PMID- 17181421
TI  - Role of pharmacogenetics in the use of CNS drugs: from drug pipeline to primary
      care?

PMID- 17181422
TI  - Stroke: ethnic differences do exist.

PMID- 17181425
TI  - In utero antiepileptic drug exposure.
AB  - Until recently, retrospective reports and small prospective studies have
      suggested that all antiepileptic drugs could be associated with teratogenicity.
      Over the last year alone, several important reports have been released from North
      America, Australia and the UK. The recently released Neurodevelopmental Effects
      of Antiepileptic Drugs study combining cohorts from the USA and the UK enrolled
      women from 1999-2004 and extended these results to include not only risks for
      major malformations, but also cognitive problems independent of anatomical
      consequences. In addition, future plans to describe the postnatal manifestations
      during the first 6 years of life may shed some light on later effects, not
      previously identified. Information from worldwide pregnancy registries are now
      reporting results that are alarmingly similar with respect to the increased risk
      of pregnancies born to women with epilepsy, consistently demonstrating greater
      degrees of major congenital malformations with the use of valproate, polytherapy
      and high-dose antiepileptic drugs administered within the first trimester of
      pregnancy.

PMID- 17181424
TI  - Role of aripiprazole in treating mood disorders.
AB  - Atypical antipsychotics have been used to treat patients with schizophrenia for
      many years, but now there is increasing evidence of their utility in the
      treatment of mood disorders. In the past few years, several atypical agents have
      received regulatory approval for use in mania. The evidence shows that atypical
      antipsychotics are effective in the treatment of manic symptoms, either alone or
      in combination with traditional mood stabilizers, such as lithium and divalproex.
      Although emerging data indicate that atypical antipsychotics will be a promising
      addition to those therapies that are currently available for managing patients
      during the maintenance phase of bipolar illness, their potential in the long-term
      management of bipolar disorder remains to be fully explored. Aripiprazole is a
      recently released antipsychotic medication that differs from other atypical
      antipsychotic agents by its mode of action as a dopamine D2 partial agonist. It
      is administered orally and has a long half-life. Randomized studies have
      demonstrated the efficacy of aripiprazole compared with placebo in the treatment
      of acute relapse of schizophrenia and schizoaffective disorder, maintenance
      treatment of schizophrenia, treatment of acute mania, and prevention of manic
      relapse in patients who responded to the drug during a manic episode. Further
      studies are ongoing in bipolar and unipolar depression. Aripiprazole is generally
      well tolerated compared with other antipsychotic medications, although commonly
      reported side effects include extrapyramidal symptoms and motoric activation
      similar to akathisia. Further studies and postmarketing data will be helpful in
      providing additional information regarding the comparative safety, efficacy and
      tolerability of aripiprazole in the treatment of affective disorders.

PMID- 17181426
TI  - Role of genetics in the diagnosis and treatment of epilepsy.
AB  - Epilepsy is a heterogeneous group of multifactorial diseases, the vast majority
      determined by interactions between many genes and environmental factors; however,
      there are rare epilepsy syndromes that can be caused by a single gene mutation
      and are inherited according to classical mendelian genetic principles. Finding
      disease-causing genetic mutations in epilepsy has provided new opportunities for
      aiding diagnosis and developing therapies. Thus, the discovery of KCNQ2 mutations
      in benign familial neonatal convulsions, SCN1A mutations in severe myoclonic
      epilepsy of infancy and in generalized epilepsy with febrile seizures plus, and
      CHRA4 and CHRB2 mutations in autosomal-dominant nocturnal frontal lobe epilepsy,
      has led to the establishment of epilepsy as a disorder of ion channel function
      and, furthermore, has led to the introduction of genetic tests that are available
      clinically to aid in diagnosis and treatment. At the present time, clinical use
      of genetic testing in epilepsy is greatest in suspected cases of severe myoclonic
      epilepsy of infancy, generalized epilepsy with febrile seizures plus, atypical
      cases of benign familial neonatal convulsions and 'occult' cases of autosomal
      dominant nocturnal frontal lobe epilepsy without a family history. Overall,
      clinical use is limited by the low number of documented disease-associated
      mutations and the uncertain clinical significance of many test results. Further
      elucidation of the relationship between gene mutations and channel function will
      add value to genetic testing in the future, as will better characterization of
      the association between gene mutations and clinical phenotypes.

PMID- 17181427
TI  - Poststroke epilepsy: occurrence, predictors and treatment.
AB  - Although a well-known clinical phenomenon, there still remain some questions
      regarding the definitions, pathophysiology and epidemiology of early and late
      poststroke seizures and of poststroke epilepsy. Poststroke seizures and epilepsy
      constitute important complications in patients surviving a stroke. Several
      studies of the prevalence and possible predictors of poststroke seizures and
      epilepsy have been undertaken during the past few decades. Unfortunately, these
      studies have not consistently used the established definitions. There are only
      few studies concerning treatment of poststroke epilepsy in the elderly,
      especially regarding the effect of the newer antiepileptic drugs. The aim of this
      article is to give an overview of the latest studies of poststroke seizures, with
      special emphasis on poststroke epilepsy, by presenting data on occurrence,
      predictors and treatment. The results from the recent studies on both poststroke
      seizures (early and late) and poststroke epilepsy are quite consistent.
      Poststroke epilepsy appears to occur in 2-4% of patients. The most convincing
      predictors of late poststroke seizures and epilepsy and treatment options are
      discussed in this review.

PMID- 17181428
TI  - Nonmotor symptoms of Parkinson's disease.
AB  - Nonmotor symptoms occur commonly in Parkinson's disease (PD) patients and are
      frequently under-recognized and undertreated. Symptoms include sleep
      abnormalities, fatigue, autonomic disturbances, mood disorders and cognitive
      dysfunction. Early recognition and treatment of nonmotor symptoms in PD is
      critical to providing optimal management. A new screening questionnaire and the
      revised Unified PD Rating Scale should assist healthcare providers to better
      identify and evaluate these symptoms. This article reviews the identification and
      treatment of nonmotor symptoms in PD.

PMID- 17181429
TI  - Fetal risks related to the treatment of multiple sclerosis during pregnancy and
      breastfeeding.
AB  - In women with multiple sclerosis, pregnancy does not have a long-term adverse
      effect on lifetime disability; however, there is an increased risk of relapses
      during the postpartum. Therapies taken during pregnancy may have adverse effects
      on pregnancy outcome. The small number of pregnancies included in most studies,
      particularly those evaluating the risks related to the administration of
      immunomodulating drugs, do not allow firm conclusions to be drawn with regards to
      their safety. Therefore, until more information regarding safety is available,
      glatiramer acetate, mitoxantrone and interferon-beta should be discontinued
      before an anticipated pregnancy. By contrast, glucocorticoids can be used to
      treat acute relapses during pregnancy.

PMID- 17181430
TI  - Highlights in muscle relaxants.
AB  - The aim of this article is to provide an overview on neuromuscular blocking
      agents and a rational selection of the most appropriate agents, along with
      pharmacological and pharmacoeconomic considerations on neuromuscular blockers and
      their antagonists. Neuromuscular blocking agents are used during anesthesia to
      facilitate endotracheal intubation and provide surgically required paralysis.
      There is continuing development in the field of neuromuscular blocking agents,
      with new products appearing at regular intervals. All new agents come at
      increased costs. The proportion of anesthesia-related drug costs on a per-patient
      basis are small and vary from country to country, but account for no more than
      12% of hospital drug budgets. However, given the large number of anesthetics
      performed over time, the total cost is significant. Moreover, such costs should
      be put into the perspective of the operating theater and patient admission costs.
      Appropriate selection of neuromuscular blocking agents can help not only to
      reduce biological costs secondary to complications, but also to make operating
      lists proceed smoothly and without incident. The paucity of outcome studies in
      relation to anesthetic drugs is not surprising given that anesthesia is used to
      facilitate the provision of therapy rather than being therapeutic in its own
      right. Accordingly, the assessment of anesthetic drugs has a different priority
      to therapeutic drugs. As anesthetic drugs are nontherapeutic, it is also
      difficult to determine the best choice of agent. However, new neuromuscular
      blocking agents are marketed on the basis of improvements in the frequency of
      side effects, safety, reliability, duration, reversibility and undesirable
      hemodynamic effects.

PMID- 17181431
TI  - Pharmacotherapy of pathological gambling: review of new treatment modalities.
AB  - Pathological gambling is classified in the Diagnostic and Statistical Manual of
      Mental Disorders, 4th Edition as an impulse-control disorder. In the
      International Classification of Diseases of the WHO, pathological gambling is
      coded under the heading of 'Habit and Impulse Disorders'. Pathological gambling
      is a chronic, progressive disorder, which has a prevalence of 1-3.4% among
      western civilizations. The enormous personal and social consequences of this
      disorder include a high rate of suicide attempts, job loss, marital and family
      problems, legal problems, and criminal behavior. Recent studies have demonstrated
      that pathological gambling patients respond well to treatment with selective
      serotonin reuptake inhibitors, mood stabilizers and opioid antagonists. These
      findings support the idea that pathological gambling and other disorders of
      impulse control may be conceptualized as part of the obsessive-compulsive
      spectrum disorders or addictive disorders. This article will discuss possible
      treatment strategies according to different behavior patterns in pathological
      gambling and also remind the physicians who intend to treat this disorder of the
      possible diagnosis of pathological gambling.

PMID- 17181432
TI  - Pandemic influenza vaccine development: time is of the essence.

PMID- 17181435
TI  - RTS,S/AS02A for malaria.
AB  - Malaria prevention and treatment is becoming increasingly difficult as drug
      resistant strains of parasites spread globally and affordable antimalarial drugs
      become ineffective. Therefore, there is a need for a safe and effective vaccine.
      In recent years, significant technological advances and an increase in funding
      for malaria vaccine research, including better public-private collaboration, have
      increased optimism that highly effective vaccines can be developed. RTS,S/AS02A
      is a novel pre-erythrocytic vaccine based on the Plasmodium falciparum
      circumsporozoite surface protein. Among all candidate vaccines developed thus
      far, only the RTS,S/AS02A vaccine has consistently been demonstrated to be well
      tolerated and provide significant protective efficacy in challenge studies and
      clinical trials in malaria-endemic countries.

PMID- 17181436
TI  - Pollinex Quattro: a novel and well-tolerated, ultra short-course allergy vaccine.
AB  - Pollinex Quattro is a novel, ultra short-course vaccine for treatment of seasonal
      allergic rhinitis from grass, tree or ragweed pollen allergy. Its unique
      formulation combines chemically modified allergens adsorbed onto a L-tyrosine
      depot to enhance tolerability with the novel adjuvant, monophosphoryl lipid A, to
      improve efficacy. Controlled clinical studies indicate that four preseasonal
      injections with grass or tree formulations significantly reduce
      rhinoconjunctivitis symptoms and medication use, as well as elevate allergen
      specific immunoglobulin G and blunt elevation of immunoglobulin E upon allergen
      exposure. Postmarketing surveillance studies indicate similar clinical outcomes.
      In all cases, the allergy vaccine was well tolerated with minimal local
      reactions, while systemic reactions were rare and mild. Results from recent
      investigational trials with grass and ragweed formulations are consistent with
      previous efficacy and safety outcomes, and will be used toward product
      registration in North America.

PMID- 17181437
TI  - Do vaccines modify the prevalence of asthma and allergies?
AB  - Epidemiological studies suggest the hypothesis that the increase in asthma and
      allergies in the industrialized world can be explained by a decline in the number
      of infectious diseases occurring during childhood. In the context of this
      'hygiene hypothesis', is immunization in early life a risk factor for promoting
      allergic diseases? The majority of studies, especially those conducted with more
      extensive populations, have not found an increased risk, and although 'not
      finding an increased risk' is not the same as 'the non-existence of any risk at
      all', it seems that the evidence is tipped in favor of the absence of risk.
      Conversely, although some surveys have described a protective effect of
      vaccination, the majority refuted this result. If there is any effect, it is
      probably a weak one.

PMID- 17181438
TI  - Postlicensure epidemiology of childhood vaccination: the Danish experience.
AB  - The efficacy, the ability to confer protection against a target disease and the
      safety of a vaccine are assessed in great detail before licensure. However,
      inherent limitations in the prelicensure assessment necessitate continued
      epidemiological evaluations of efficacy and safety issues after the introduction
      of vaccines into use. In Denmark, the opportunities available for epidemiological
      research are unique. In 2001, an initiative was undertaken to take advantage of
      these opportunities to study the postlicensure epidemiology of childhood
      vaccination with respect to effectiveness and safety. First, we describe the
      unique opportunities for postlicensure research in Denmark with respect to the
      data sources available and the epidemiological and statistical methods used. We
      then describe a number of recent postlicensure studies of effectiveness and
      safety that took advantage of these opportunities. Specifically, studies on the
      effectiveness of Haemophilus influenzae type b vaccination, the effectiveness of
      pertussis vaccination, the impact of a preschool pertussis booster on infant
      pertussis, measles-mumps-rubella vaccine and autism, thimerosal-containing
      vaccine and autism, measles-mumps-rubella vaccine and febrile seizures, childhood
      vaccination and Type 1 diabetes, and childhood vaccination and nontargeted
      infectious disease are discussed.

PMID- 17181439
TI  - Nasopharyngeal colonization: a target for pneumococcal vaccination.
AB  - The pneumococcal conjugate vaccine (PCV), licensed in 2000, is highly efficient
      in preventing serious disease caused by serotypes in the vaccine and also
      prevents symptomless colonization of the nasopharynx. Prevention of this first
      step in the infection cycle has important consequences: it reduces chances of
      spread of the infection and indirectly protects from disease. Through these
      indirect effects, the protection afforded by the vaccine extends to the whole
      population, including those not vaccinated (herd immunity). Already now, after 5
      years of wide use of PCV for infant immunization in the USA, more cases are
      prevented through the indirect effects than by vaccine-induced immunity in those
      vaccinated. The extended protection increases the cost-effectiveness of PCV and
      should clearly encourage its use in poorly resourced countries. However, the
      accumulated experience also shows that the herd immunity, due to PCV, is partly
      offset by replacement of the vaccine serotypes by other, nonvaccine serotypes.
      Owing to the general reduced virulence of the latter, this has only had a modest
      effect on disease, but the possibility of more virulent nonvaccine serotypes
      arising cannot be ignored and should be the focus of continued surveillance.

PMID- 17181440
TI  - Live-attenuated Shigella vaccines.
AB  - Several live-attenuated Shigella vaccines, with well-defined mutations in
      specific genes, have shown great promise in eliciting significant immune
      responses when given orally to volunteers. These responses have been measured by
      evaluating antibody-secreting cells, serum antibody levels and fecal
      immunoglobulin A to bacterial lipopolysaccharide and to individual bacterial
      invasion plasmid antigens. In this review, data collected from volunteer trials
      with live Shigella vaccines from three different research groups are described.
      The attenuating features of the bacterial strains, as well as the immune response
      following the use of different dosing regimens, are also described. The responses
      obtained with each vaccine strain are compared with data obtained from challenge
      trials using wild-type Shigella strains. Although the exact correlates of
      protection have not been found, some consensus may be derived as to what may
      constitute a protective immune response. Future directions in the field of live
      Shigella vaccines are also discussed.

PMID- 17181441
TI  - Towards a universal group B Streptococcus vaccine using multistrain genome
      analysis.
AB  - Genomics has revolutionized the way in which novel vaccine candidates are
      identified for the development of efficacious vaccines. Reverse vaccinology,
      whereby all candidates of interest are identified by analysis of a pathogen's
      genome, enables characterization of many candidates simultaneously. It
      accelerates the initial steps of vaccine development and greatly increases the
      chances of obtaining reliable candidates or cocktails thereof. The availability
      of one or two genome sequences for any given pathogen provides access to strain
      specific vaccine candidates but often fails to identify candidates that would
      confer general protection. The analysis of multiple genomes of group B
      Streptococcus revealed tremendous diversity and identified candidates that are
      not shared by all the strains sequenced, but provide general protection when
      combined.

PMID- 17181442
TI  - Live vaccines for human metapneumovirus designed by reverse genetics.
AB  - Human metapneumovirus (HMPV) was first described in 2001 and has quickly become
      recognized as an important cause of respiratory tract disease worldwide,
      especially in the pediatric population. A vaccine against HMPV is required to
      prevent severe disease associated with infection in infancy. The primary strategy
      is to develop a live-attenuated virus for intranasal immunization, which is
      particularly well suited against a respiratory virus. Reverse genetics provides a
      means of developing highly characterized 'designer' attenuated vaccine
      candidates. To date, several promising vaccine candidates have been developed,
      each using a different mode of attenuation. One candidate involves deletion of
      the G glycoprotein, providing attenuation that is probably based on reduced
      efficiency of attachment. A second candidate involves deletion of the M2-2
      protein, which participates in regulating RNA synthesis and whose deletion has
      the advantageous property of upregulating transcription and increasing antigen
      synthesis. A third candidate involves replacing the P protein gene of HMPV with
      its counterpart from the related avian metapneumovirus, thereby introducing
      attenuation owing to its chimeric nature and host range restriction. Another live
      vaccine strategy involves using an attenuated parainfluenza virus as a vector to
      express HMPV protective antigens, providing a bivalent pediatric vaccine.
      Additional modifications to provide improved vaccines will also be discussed.

PMID- 17181443
TI  - Therapeutic vaccination in chronic hepatitis B virus carriers.
AB  - Despite effective prophylactic vaccines against hepatitis B virus existing for
      over 20 years, more than 2.5 billion people worldwide have been exposed to the
      disease and approximately 370 million people are chronically infected with it.
      Chronic infection in more than two thirds of infected patients results in chronic
      liver disease, which may lead to cirrhosis, exposure to noncarcinomatous
      complications and hepatocellular carcinoma. Currently available therapies fail to
      allow complete control of viral replication in most patients. Viral persistence
      has been associated with a defect in the development of hepatitis B virus
      specific cellular immunity. Immunomodulatory strategies to boost or to broaden
      the weak virus-specific T-cell response have been proposed to bypass the chronic
      hepatitis B infection, including hepatitis B virus envelope- and nucleocapsid
      based vaccines, and new formulations for recombinant and DNA-based vaccines,
      which are currently being evaluated in clinical trials.

PMID- 17181444
TI  - Cancer immunotherapy using virally transduced dendritic cells: animal studies and
      human clinical trials.
AB  - The immune system uses a process known as 'immunosurveillance' to help prevent
      the outgrowth of tumors. In cancer immunotherapy, a major goal is for immunity
      against tumor-associated antigens to be generated or strengthened in patients. To
      achieve this goal, several approaches have been tested, including the use of
      highly potent antigen-presenting cells called dendritic cells (DCs), which can
      activate T cells efficiently. Presentation of peptides derived from tumor
      antigens on the surface of DCs can stimulate strong antitumor immunity. Using
      recombinant viral vectors encoding tumor-associated antigens, DCs can be
      engineered efficiently to express sustained levels of tumor-antigen peptides.
      This review discusses the effectiveness of virally transduced DCs in treating
      tumors and generating antigen-specific T-cell responses. It covers mouse and
      nonhuman primate studies, preclinical in vitro human cell experiments and
      clinical trials.

PMID- 17181445
TI  - Tamoxifen-induced non-alcoholic steatohepatitis: where are we now and where are
      we going?
AB  - Tamoxifen is a cheap and effective estrogen-receptor antagonist, used as the
      adjuvant hormonal treatment of choice in women with estrogen-receptor-positive
      breast cancer. Tamoxifen-induced non-alcoholic steatohepatitis (NASH) may
      increase the demand on oncologists, not only with regard to screening for
      diabetes, but also for the suggested link of NASH with high incidence of coronary
      heart disease. At present, there is no guideline for treatment of hyperlipidaemia
      associated with tamoxifen-induced NASH. However, exemstane (and other aromatase
      inhibitors) has been shown to lower triglyceride and have a neutral effect on low
      denisty lipoprotein and cholesterol levels. These may be alternative agents if
      severe progressive liver disease or hyperlipidaemia were encountered with
      tamoxifen administration. Other lipid-lowering medications may have potential
      benefits in the treatment of tamoxifen-induced NASH and is discussed in this
      article.

PMID- 17181446
TI  - Insulin glulisine: efficacy and safety compared with other rapid-acting insulin
      analogues.
AB  - Glulisine insulin is the latest addition to the class of rapid-acting insulin
      analogues. It is important that it is comparable in safety not only to human
      regular insulin, but also to the well established analogue insulins, aspart and
      lispro. In this summary the evidence comparing the safety and efficacy of
      glulisine with its counterpart insulins in various groups of diabetic patients is
      discussed.

PMID- 17181447
TI  - Do cheap internet drugs threaten the safety of the doctor-patient relationship?
AB  - During traditional office visits, trusted physicians give their patients careful
      and leisurely diagnostic attention, communicate sound and understandable clinical
      impressions and, more often than not, write prescriptions that can be filled at
      convenient neighborhood pharmacies. Or do they? In reality, harried doctors rush
      through appointments, leaving patients confused about prescriptions they cannot
      afford, either because their insurance plans do not cover the recommended
      medication or because they lack the cash to pay out of pocket for obscenely
      priced products. Internet pharmaceutical acquisition offers a cheap alternative.
      Or does it?

PMID- 17181448
TI  - The safety of asthma medications during pregnancy.
AB  - This article reviews the literature on asthma or use of antiasthmatic drugs
      during pregnancy, the impact on pregnancy and delivery outcome, and on the infant
      born. Some anomalies have been demonstrated. It is unclear if these are due to
      asthma or are the effect of antiasthma drug use. The former explanation appears
      to be most likely, and the outcome appears to co-vary with the severity of the
      disease. Therefore, an adequate therapy of asthma is important during pregnancy,
      and although a small increase in certain congenital malformations may exist, this
      is of little significance for the individual patient. Further efforts should be
      made to isolate the possible specific effects of antiasthmatic drugs, notably for
      recent additions to the therapeutic arsenal.

PMID- 17181449
TI  - Uses and complications of mitomycin C in ophthalmology.
AB  - Mitomycin C is a chemotherapeutic agent that acts by inhibiting DNA synthesis.
      Its use and application in ophthalmology has been increasing in recent years
      because of its modulatory effects on wound healing. Current applications include
      pterygium surgery, glaucoma surgery, corneal refractive surgery, cicatricial eye
      disease, conjunctival neoplasia and allergic eye disease. Although it has been
      used successfully in these conditions, it has also been associated with
      significant complications. This article reviews the current trends and uses of
      mitomycin C in the eye and its reported complications.

PMID- 17181450
TI  - Is it safe to use topical NSAIDs for corneal sensitivity in Sjogren's syndrome
      patients?
AB  - Sjogren's syndrome dry eye is an inflammatory disease accompanied by an
      impairment of the autonomous nervous system of the ocular surface. The therapy
      for this condition is shifting from the mere tear replacement to a more complex
      approach including an anti-inflammatory treatment. Clinical trials have evidenced
      that the use of NSAIDs is followed by a reduction of the ocular discomfort
      symptoms in dry-eye patients. However, sporadic case reports of corneal melting
      in dry-eye subjects who underwent surgical procedures has brought attention to
      the possible effect that NSAIDs may have on corneal sensitivity. Therefore, the
      effect of NSAID treatment on corneal sensitivity in normal subjects and in
      patients with dry eye was studied. The results of these trials seem to
      demonstrate that some NSAIDs, diclofenac in particular, have the effect of
      reducing corneal sensitivity both in normal subjects and in patients with dry
      eye. Therefore, NSAIDs should be used with caution in Sjogren's syndrome
      patients.

PMID- 17181451
TI  - The side effects of the prostaglandin analogues.
AB  - In the last decade topically applied prostaglandin F2alpha analogues
      (bimatoprost, latanoprost, travoprost and unoprostone) have become widely used as
      a means to reduce elevated intraocular pressure in patients with glaucoma and
      ocular hypertension. These molecules all have similar side-effect profiles, which
      include both side effects that occur frequently (e.g., conjunctiva hyperaemia,
      increase of iris pigmentation and eyelash changes) and rare adverse reactions
      (e.g., periocular pigmentation, damage to the blood-aqueous barrier and cystoid
      macular oedema). Conjunctiva hyperaemia, eyelash changes and cystoid macular
      oedema are reversible, but certain other side effects, such as increased iris
      pigmentation, are not. However, the systemic side-effect profile is favourable
      for all the prostaglandin analogues, and some of the local side effects are only
      of cosmetic significance. Numerous clinical studies suggest that discontinuing
      treatment with prostaglandin analogues on account of their side effects is rare
      in clinical practice.

PMID- 17181452
TI  - Safety of topotecan in the treatment of recurrent small-cell lung cancer and
      ovarian cancer.
AB  - The topoisomerase I inhibitor, topotecan, is approved for the treatment of
      recurrent small-cell lung cancer (SCLC) and ovarian cancer (OC). Patients with
      recurrent SCLC and OC typically experience multiple relapses and receive multiple
      rounds of chemotherapy. In these settings, disease stabilisation is considered a
      treatment benefit, and quality-of-life effects and cumulative toxicities of
      treatments should be considered. Many patients with recurrent cancer may be
      predisposed to treatment-related adverse events because of advanced age, renal
      impairment or extensive prior therapy. The standard regimen of topotecan, 1.5
      mg/m(2) on days 1-5 of a 21-day cycle, has generally mild nonhaematological
      toxicity and a well-defined haematological toxicity profile characterised by
      reversible and noncumulative neutropenia. Alternative regimens may lower the
      incidence of haematological toxicities and maintain antitumour efficacy.
      Topotecan may provide physicians with a versatile therapeutic option for the
      treatment of patients with relapsed SCLC or OC.

PMID- 17181453
TI  - Safety considerations for erythropoietin treatment in patients with cancer.
AB  - Cancer-related anaemia, which affects many patients with cancer, can effectively
      be treated by erythropoietic proteins. Erythropoietic proteins increase
      haemoglobin levels, reduce the risk for transfusions and also improve the quality
      of life of patients. When used according to published practice guidelines, these
      proteins benefit many patients and are generally well tolerated. Important side
      effects are hypertension and thromboembolic events, either of which occurs in <
      10% of the patients. Administration only in anaemic patients, avoidance of target
      haemoglobin levels > 130 g/l, proper dose adjustments and close monitoring during
      treatment will ensure the clinical safety of these proteins. However, the
      association between erythropoietic proteins and outcome of anticancer therapy,
      including survival, requires further study.

PMID- 17181454
TI  - Prediction of drug-induced intrahepatic cholestasis: in vitro screening and QSAR
      analysis of drugs inhibiting the human bile salt export pump.
AB  - Drug-induced intrahepatic cholestasis is one of the major causes of
      hepatotoxicity, which often occur during the drug discovery and development
      process. Human ATP-binding cassette transporter ABCB11 (sister of P
      glycoprotein/bile salt export pump) mediates the elimination of cytotoxic bile
      salts from liver cells to bile, and, therefore, plays a critical role in the
      generation of bile flow. The authors have recently developed in vitro high-speed
      screening and quantitative structure-activity relationship analysis methods to
      investigate the interaction of ABCB11 with a variety of compounds. Based on the
      extent of inhibition of the bile salt export pump, the authors analysed the
      quantitative structure-activity relationship to identify chemical groups closely
      associated with the inhibition of ABCB11. This approach provides a new tool to
      predict compounds with a potential risk of drug-induced intrahepatic cholestasis.

PMID- 17181457
TI  - Psychosocial correlates of dietary intake among overweight and obese men.
AB  - OBJECTIVES: To investigate the relationship between theoretically based
      psychosocial constructs and dietary components among overweight men. METHODS:
      Participants were 441 men (BMI M = 34.2). Psychosocial constructs included self
      efficacy, decisional balance, social support, and behavior change strategies.
      Dietary components were fat, fiber, and fruit and vegetable intake. RESULTS: All
      significant findings were in the expected direction. Multiple regression models
      indicated that the psychosocial factors accounted for the most variance in
      vegetable intake (R(2)=.13) and the least variance in fat (R(2)=.05).
      CONCLUSIONS: Theoretically based psychosocial constructs were related to
      overweight men's dietary intake and have potential for use in tailored behavior
      change interventions.

PMID- 17181458
TI  - Demographic, health, and behavioral factors associated with smoking in adults
      with type 1 or type 2 diabetes.
AB  - OBJECTIVES: To identify demographic, health, and behavioral factors associated
      with smoking behavior in adults with diabetes. METHODS: Canadian adults 18+ years
      with type 1 (n=697) or type 2 (n=1621) were investigated. Logistic regression
      analyses were conducted separately for both diabetes subgroups. RESULTS: When
      comparing never versus ever smokers, never versus current smokers, and former
      smokers who quit versus current smokers, similarities and differences for
      demographic, health, and behavioral factors were found for the 2 diabetes
      subgroups. CONCLUSIONS: Diabetes type, demographic, health, and behavioral
      factors should be considered when tailoring smoking cessation and prevention
      programs.

PMID- 17181459
TI  - Inhalant use among indiana school children, 1991-2004.
AB  - OBJECTIVE: To examine the prevalence and trend of inhalant use among Indiana
      public school students. METHODS: The Alcohol, Tobacco, and Other Drug Use among
      Indiana Children and Adolescents surveys conducted annually between 1991 and 2004
      were reanalyzed using 2-way moving average, Poisson regression, and ANOVA tests.
      RESULTS: The prevalence had increased during 1991- 1997, decreased during 1997-
      2002, and increased again since 2003. Poisson model estimated an average annual
      decrease rate of 5.6%. The intensity of inhalant use had also decreased. More
      males and Hispanics use inhalants. CONCLUSION: Inhalant use needs to be addressed
      in drug prevention programs.

PMID- 17181460
TI  - Effectiveness of a nutrition intervention with rural low-income women.
AB  - OBJECTIVES: To evaluate Cookin' Up Health, a computer-based interactive nutrition
      intervention. METHODS: After randomization to intervention and control groups,
      262 women in rural clinics in West Virginia completed both a baseline and 3-month
      follow-up survey. RESULTS: Compared to the control group, the intervention group
      had significantly improved scores on knowledge of dietary fats, food label
      reading, and readiness to eat 5 fruits and vegetables a day and foods lower in
      fat. CONCLUSIONS: This brief interactive nutrition intervention shows potential
      as a strategy to begin the process of change, but follow-up may be needed for
      actual behavior change to occur.

PMID- 17181462
TI  - Cigarette and nargileh smoking practices among school students in Beirut,
      Lebanon.
AB  - OBJECTIVES: To determine the prevalence and predictors of smoking nargileh and/or
      cigarettes among school students in Greater Beirut, Lebanon. METHODS: A
      proportionate random sample of 2443 students from 13 public and private schools
      was selected and asked to complete self-administered anonymous questionnaires.
      RESULTS: The prevalence of smoking cigarettes only, nargileh only, and both was
      2.5%, 25.6%, and 6.3%, respectively. Stepwise regression analyses revealed that
      the predictors of smoking for either type are different, whereby nargileh smoking
      is more culturally accepted than cigarette smoking. CONCLUSIONS: Design
      interventions to increase awareness towards the hazards of the misconceived
      harmless effects of nargileh smoking.

PMID- 17181461
TI  - Evaluation of a social marketing campaign targeting preschool children.
AB  - OBJECTIVES: To determine the effectiveness of a pilot social marketing program to
      increase preschoolers' willingness to try new foods. METHODS: Four Head Start
      centers participated (2 experimental, 2 control) in a study using a quasi
      experimental design. Experimental sites received a 12-week intervention developed
      using social marketing techniques. The program was evaluated via preference
      assessments, classroom observations, and teacher surveys. RESULTS: Increased
      preference for and willingness to try new foods were observed in children from
      the experimental sites (P<0.05). The program was positively received by Head
      Start staff. CONCLUSIONS: A social marketing campaign is an effective method to
      reduce children's neophobia.

PMID- 17181463
TI  - Awareness and adoption of a nationally disseminated dietary curriculum.
AB  - OBJECTIVE: To identify regional, organizational, and personal characteristics
      that predict awareness and adoption of a dietary curriculum training and CD among
      educators. METHODS: A cross-sectional study of educators (n=675) representing 48
      states report program awareness and factors that influenced adoption. RESULTS:
      Among those surveyed, 354 educators were aware (52%) of the CD and 192 educators
      adopted it (54%). Adopters were nearly 8 times more likely to identify training
      time and nearly 7 times more likely to identify CD training method as influencing
      adoption. CONCLUSION: Although regional and organizational characteristics are
      predictors of awareness, these variables were less likely to predict adoption of
      such programs.

PMID- 17181464
TI  - Structural equation modeling: a primer for health behavior researchers.
AB  - OBJECTIVE: To introduce the state of the art of structural equation modeling
      (SEM). METHOD: This primer is organized in a manner allowing readers to review
      any one of 5 freestanding sections. RESULTS: SEM maintains several advantages
      over regression and other multivariate techniques. Through a 2-step modeling
      process, SEM strengthens research by allowing for the specification of complex,
      theory-driven models that can be tested with empirical data. Although use of SEM
      alone is not a magic solution, new software developments provide users with
      unparalleled flexibility for improving research. CONCLUSION: SEM must be thrust
      into the daily vocabulary and routine practice of health behavior researchers.

PMID- 17181466
TI  - Perceived goal ownership, regulatory goal cognition, and health behavior change.
AB  - OBJECTIVE: To investigate the links among perceived goal ownership, regulatory
      goal cognition, and health behavior change. METHODS: A sample of 390 college
      students completed measures of (a) perceived goal ownership for a goal related to
      a health behavior that they, their dating partner, or both were seeking to
      change, (b) 9 aspects of regulatory goal cognition, and (c) health behavior
      change. RESULTS: As compared to participants with self-set and joint-set goals,
      participants with partner-set goals reported less adaptive regulatory goal
      cognition and were less likely to report positive changes in health behavior.
      CONCLUSION: Efforts to change dating partner's health behaviors should be framed
      as joint-set goals.

PMID- 17181465
TI  - Measurement of perceived school climate for active travel in children.
AB  - OBJECTIVES: To describe the development of an original scale that measures
      perceived school climate for active travel in fourth- and fifth-grade girls and
      boys. METHODS: The data were analyzed using confirmatory factor analysis (CFA) to
      provide evidence of factorial validity, factorial invariance, and construct
      validity. RESULTS: The CFA supported the fit of a 3-factor (encouragement,
      praise, and importance) correlated model for the school climate for active travel
      measure. This hierarchical model was invariant between sex and across a 7-month
      time period, and initial evidence for construct validity was provided.
      CONCLUSIONS: School climate for active travel is a measurable construct, and
      preliminary evidence suggests relationships with more support for active travel
      from friends and family.

PMID- 17181468
TI  - Proteome chips: a future perspective.

PMID- 17181470
TI  - Proteomics: challenges and emerging technologies, EuroSciCon.

PMID- 17181471
TI  - Fourth International Conference on High-Pressure Biosciences and Biotechnology.

PMID- 17181472
TI  - Multiplexed immunofluorescence microscopy for the interrogation of cellular
      protein complexes.
AB  - Knowing that a specific protein is present within a cell provides little insight
      into its function. In a study by Schubert and colleagues, the investigators
      present a multidimensional method that utilizes fluorescence microscopy and
      automated antibody introduction and detection, which is potentially capable of
      localizing hundreds of proteins within individual cells. The method, referred to
      as multiepitope-ligand cartography, is validated in the analysis of cell-surface
      receptors in peripheral mononuclear blood cells, and then used to map protein
      complexes in a series of disease models, including psoriasis and chronic
      constriction injury. Within each experiment, the locales of each protein are
      presented in a binary format and the data are interpreted to recognize specific
      proteins that control the topology of the protein network. The hope is that by
      identifying partnerships between proteins and those proteins that are most
      responsible for these interactions, novel diagnostic features and therapeutic
      targets can be established.

PMID- 17181473
TI  - Top-down mass spectrometry of integral membrane proteins.
AB  - Top-down mass spectrometry focuses on intact proteins, thereby avoiding loss of
      information accompanying 'shotgun' protocols that reduce the proteome to a
      collection of peptides. A suite of liquid-chromatography technologies has been
      developed for purification of intact integral membrane proteins in
      aqueous/organic solvent mixtures compatible with biological 'soft-ionization'
      mass spectrometry, preserving covalent structure into the gas phase. Multiply
      charged protein ions are fragmented in the gas phase, using either collision
      activated or electron-capture dissociation, thus yielding complex spectra of
      sequence-dependent product ions that collectively define the original native
      covalent state of an intact protein. Top down offers a more detail-orientated
      approach to post-transcriptional and post-translational diversity allowing an
      enhanced insight beyond genomic translation, which has now extended into the
      bilayer proteome.

PMID- 17181475
TI  - Overcoming the dynamic range problem in mass spectrometry-based shotgun
      proteomics.
AB  - Protein profiling using mass spectrometry technology has emerged as a powerful
      method for analyzing large-scale protein-expression patterns in cells and
      tissues. However, a number of challenges are present in proteomics research, one
      of the greatest being the high degree of protein complexity and huge dynamic
      range of proteins expressed in the complex biological mixtures, which exceeds six
      orders of magnitude in cells and ten orders of magnitude in body fluids. Since
      many important signaling proteins have low expression levels, methods to detect
      the low-abundance proteins in a complex sample are required. This review will
      focus on the fundamental fractionation and mass spectrometry techniques currently
      used for large-scale shotgun proteomics research.

PMID- 17181474
TI  - Proteomic applications of protein quantification by isotope-dilution mass
      spectrometry.
AB  - Over the decades, isotope-dilution mass spectrometry (IDMS) has been implemented
      extensively for accurate quantification of drugs, metabolites and peptides in
      body fluids and tissues. More recently, it has been extended for quantifying
      specific proteins in complex mixtures. In this extended methodology, proteins are
      subjected to endoprotease action and specific resultant peptides are quantified
      by using synthetic stable isotope-labeled standard (SIS) peptides and IDMS. This
      article outlines the utilities and applications of quantifying proteins by IDMS,
      emphasizing its complementary value to global survey-based proteomic studies. The
      potential of SIS peptides to provide quantitative insights into cell signaling is
      also highlighted, with specific examples. Finally, we propose several novel mass
      spectrometric data acquisition strategies for large-scale applications of IDMS
      and SIS peptides in systems biology and protein biomarker validation studies.

PMID- 17181476
TI  - Genome annotating proteomics pipelines: available tools.
AB  - Proteomics based on tandem mass spectrometry is a powerful tool for identifying
      novel biomarkers and drug targets. Previously, a major bottleneck in high
      throughput proteomics has been that the computational techniques needed to
      reliably identify proteins from proteomic data lagged behind the ability to
      collect the immense quantity of data generated. This is no longer the case, as
      fully automated pipelines for peptide and protein identification exist, and these
      are publicly and privately accessible. Such pipelines can automatically and
      rapidly generate high-confidence protein identifications from large datasets in a
      searchable format covering multiple experimental runs. However, the main
      challenge for the community now is to use these resources as they are, by taking
      full advantage of the pooling of information, so that the next barrier in our
      understanding of biology may be broken. There are currently two pipelines in the
      public domain that provide such potential: PeptideAtlas and the Genome Annotating
      Proteomic Pipeline. This review will introduce their features in the context of
      high-throughput proteomics, and provide indicative results as to their usefulness
      and usability through a side-by-side comparison of results obtained when
      processing a set of human plasma samples.

PMID- 17181477
TI  - Mass spectrometry-based immunoassays for the next phase of clinical applications.
AB  - Recent applications of affinity mass spectrometry into clinical laboratories
      brought a renewed interest in immunoaffinity mass spectrometry as a more specific
      affinity method capable of selectively targeting and studying protein biomarkers.
      In mass spectrometry-based immunoassays, proteins are affinity retrieved from
      biological samples via surface-immobilized antibodies, and are then detected via
      mass spectrometric analysis. The assays benefit from dual specificity, which is
      brought about by the affinity of the antibody and the protein mass readout. The
      mass spectrometry aspect of the assays enables single-step detection of protein
      isoforms and their individual quantification. This review offers a comprehensive
      review of mass spectrometry-based immunoassays, from historical perspectives in
      the development of the immunoaffinity mass spectrometry, to current applications
      of the assays in clinical and population proteomic endeavors. Described in more
      detail are two types of mass spectrometry-based immunoassays, one of which
      incorporates surface plasmon resonance detection for protein quantification. All
      mass spectrometry-based immunoassays offer high-throughput targeted protein
      investigation, with clear implications in clinical research, encompassing
      biomarker discovery and validation, and in diagnostic settings as the next
      generation immunoassays.

PMID- 17181478
TI  - Direct class I HLA antigen discovery to distinguish virus-infected and cancerous
      cells.
AB  - Class I human leukocyte antigen molecules are nature's proteome-scanning chips,
      presenting thousands of endogenously loaded peptides on the surface of virtually
      every cell in the body. Cytotoxic T cells survey the class I human leukocyte
      antigen peptide cargo presented, recognize peptides unique to unhealthy cells and
      destroy diseased cells. A precise understanding of how class I molecules
      distinguish diseased cells is positioned to drive immune-based diagnostics,
      therapies and vaccines. When identifying epitopes unique to unhealthy cells, the
      most experimentally direct approach is to examine the class I-presented peptides
      of infected/cancerous cells. Here we discuss the strategies adapted for protein
      production, protein/peptide purification, peptide separation and for maintaining
      experimental reproducibility during the direct characterization of class I human
      leukocyte antigen peptides.

PMID- 17181479
TI  - Protein profiling of pancreatic islets.
AB  - The insulin-producing beta cell in the islet of Langerhans is central in glucose
      homeostasis. Its dysfunction is part of the pathogenesis of both Type 1 and 2
      diabetes mellitus. In both forms of the disease, there is a cytotoxic component
      either induced by cytokines, as in Type 1 diabetes, or by elevated levels of
      glucose and fatty acids, as in Type 2 diabetes. To find the mechanisms
      responsible for the cytotoxic effects of these compounds proteomic approaches
      with 2D gel electrophoresis and surface-enhanced laser desorption/ionization time
      of-flight mass spectrometry have been undertaken. In this article, we describe
      these methods, and other methodological aspects of protein profiling of
      pancreatic islets, and summarize the results obtained with these methods.

PMID- 17181480
TI  - Contribution of mass spectrometry-based proteomics to immunology.
AB  - Antigen processing forwards various information about the cellular status and the
      proteome to the cell surface for scrutiny by the cellular immune system. Thus the
      repertoire of major histocompatibility complex (MHC)-bound peptides and the MHC
      ligandome, indirectly mirrors the proteome in order to make alterations instantly
      detectable and, if necessary, to oppose them. Mass spectrometry is the core
      technology for analysis of both proteome and MHC ligandome and has evoked several
      strategies to gain qualitative and quantitative insight into the MHC-presented
      peptide repertoire. After immunoaffinity purification of detergent-solubilized
      peptide-MHC complexes followed by acid elution of peptides, liquid chromatography
      mass spectrometry is applied to determine individual peptide sequences and, thus,
      allow qualitative characterization of the MHC-bound repertoire. Differential
      quantification based on stable isotope labeling enables the relative comparison
      of two samples, such as diseased and healthy tissue. Targeted searches for
      certain natural ligands, such as the 'predict-calibrate-detect' strategy, include
      motif-based epitope prediction and calibration with reference peptides. Thus,
      various approaches are now available for exposing and understanding the
      intricacies of the MHC ligand repertoire. Analysis of differences in the MHC
      ligandome under distinct conditions contributes to our understanding of basic
      cellular processes, but also enables the formulation of immunodiagnostic or
      immunotherapeutic strategies.

PMID- 17181481
TI  - Immunoprevention of cancer: time to reconsider timing of vaccination against
      cancer.

PMID- 17181483
TI  - Genistein and resveratrol: mammary cancer chemoprevention and mechanisms of
      action in the rat.
AB  - The environment, including diet, plays a critical role in a woman's subsequent
      risk of breast cancer. Two dietary polyphenols that have received attention from
      the health and research communities for their ability to protect against breast
      cancer are: genistein, a component of soy; and resveratrol, a phytoalexin found
      in red grapes and red wine. We and others have shown that both genistein and
      resveratrol can protect against mammary cancer in rodents. The timing of exposure
      to genistein appears critical for its mammary protective effects. It has been
      reported that genistein early in life causes enhanced mammary gland
      differentiation, alterations in cell proliferation and apoptosis, and
      upregulation of tumor-suppressor genes. With resveratrol in the diet, changes in
      cell proliferation and apoptosis in terminal ductal structures of the mammary
      gland might help to explain its protective effects. We conclude that genistein
      and resveratrol can protect against breast cancer by regulating important mammary
      growth and differentiation pathways.

PMID- 17181484
TI  - Small-cell carcinoma of the urinary bladder: diagnosis and management.
AB  - Small-cell carcinoma of the urinary bladder (SCCUB) accounts for less than 1% of
      all cancers arising in the urinary bladder. Current diagnosis and management of
      SCCUB are often patterned after small-cell lung cancer (SCLC). However, SCCUB
      therapy is different from that for SCLC. For example, many patients with SCCUB
      undergo local resection, which is rarely performed in SCLC. As in SCLC, platinum
      etoposide combination chemotherapy is employed as the main systemic treatment
      option for SCCUB. Chemotherapy is usually combined with other therapeutic
      modalities, especially in patients whose disease is limited to the locoregional
      area. Owing to the rarity of this malignancy, no prospective study has been
      performed that establishes the efficacy and duration of chemotherapy or the
      relative efficacy of platinum-etoposide versus other chemotherapeutic regimens.
      This article provides a comprehensive review of the current status of SCCUB
      diagnosis and management, as well as some unique insights into this rare tumor.

PMID- 17181485
TI  - Urachal carcinoma: surgical and chemotherapeutic options.
AB  - The urachal ligament is an embryologic remnant connecting the dome of the bladder
      to the umbilicus via the ligamentum commune. Autopsy series suggest that in
      approximately a third of subjects, the urachal remnant may persist with tubular
      or cystic structures. However, tumors of this site are extremely rare. Patients
      usually present with hematuria and upon imaging, have evidence of a cystic or
      solid structure in the bladder dome or in the bladder midline. If a biopsy
      confirms adenocarcinoma, these tumors should be considered an urachal cancer
      until proven otherwise. Although there are no prospective clinical trials
      reported to date, large single-institution reports suggest surgical resection
      with a partial cystectomy and en bloc resection of the urachal ligament with
      umbilicus as the treatment of choice in the setting of localized disease.
      Although there is currently no definitive role for neoadjuvant or adjuvant
      chemotherapy in this tumor, risk factors predicting progression may allow for the
      selection of patients at higher relapse risk for prospective studies.
      Unfortunately, there are many patients who present with metastatic disease that
      currently is not likely to be curable. There is no standard chemotherapy regimen
      for these patients; however, there is new-found hope with a currently accruing
      clinical trial exploring a 5-fluorouracil-based chemotherapy combination in this
      patient population.

PMID- 17181487
TI  - Percutaneous radiofrequency ablation: minimally invasive therapy for renal
      tumors.
AB  - Currently, up to 60% of renal tumors are detected incidentally by abdominal
      imaging. Most of these tumors are small and localized to the kidney. Owing to the
      shift to lower stage at diagnosis, radical nephrectomy has fallen out of favor
      and has been replaced by nephron-sparing surgery. Currently, partial nephrectomy
      is the treatment of choice for patients with small renal tumors. As the trend
      towards less invasive therapy continues, laparoscopic and percutaneous ablation
      techniques have gained popularity for the treatment of renal tumors in patients
      who are high-risk surgical candidates, or have a solitary kidney, limited renal
      function or multifocal disease. Percutaneous radiofrequency ablation is a safe,
      minimally invasive treatment option for those patients.

PMID- 17181486
TI  - Superficial bladder cancer: part 1. Update on etiology, classification and
      natural history.
AB  - Superficial 'nonmuscle-invasive' bladder tumors represent a heterogeneous group
      of cancers, which include those that are papillary in nature and limited to the
      mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that
      invade the submucosa or lamina propria (T1). The natural history of these bladder
      cancers is that of disease recurrence and progression to higher grade and stage.
      Furthermore, recurrence and progression rates of superficial bladder cancer vary
      according to several tumor characteristics. The goal in the treatment of
      superficial bladder cancer is twofold: reducing tumor recurrence and the
      subsequent need for additional therapies, such as cystoscopy, transurethral
      resections, intravesical therapy and the morbidity associated with these
      treatments; and preventing tumor progression and the subsequent need for more
      aggressive therapy, such as radical cystectomy. The administration of
      intravesical chemotherapy and immunotherapy has become an important component in
      accomplishing these goals. This update is the first part of two articles
      reviewing important contemporary concepts in the etiology, classification and
      natural history of superficial bladder cancer, while part II of the series will
      review and highlight important aspects in management of superficial bladder
      cancer.

PMID- 17181488
TI  - Partial nephrectomy achieves local tumor control and prevents chronic kidney
      disease.
AB  - Over the last 10 years, a rapidly changing clinical landscape has created an
      optimal environment to expand the use of partial nephrectomy for the treatment of
      renal cortical tumors. The main factors responsible for the increasing use of
      partial nephrectomy relate to the appreciation of the diversity of renal cortical
      tumor histology, the tumor stage and size migration associated with their
      incidental detection, and the oncological efficacy of partial nephrectomy for
      tumors of 7 cm or smaller. Evidence has now emerged that radical nephrectomy
      performed during the treatment of a small renal mass may further reduce an
      already impaired baseline renal function and place the patient in the realm of
      chronic kidney disease. Important new information concerning chronic kidney
      disease, a condition far more prevalent in the aging US population than
      previously appreciated, and its associated cardiovascular morbidity and
      mortality, now places maximal renal functional preservation on a par with local
      tumor control as surgical plans are formulated for the resection of a small renal
      cortical tumor.

PMID- 17181489
TI  - Molecularly targeted therapy in renal cell carcinoma: where do we go from here?
AB  - The angiogenic phenotype of renal cell carcinoma results from vascular
      endothelial growth factor pathway activation. Several different strategies
      targeting various aspects of the pathway have emerged as clinically relevant
      therapeutics in metastatic renal cell carcinoma. Key clinical data regarding
      these approaches are presented in this article. Furthermore, there are several
      considerations as to the further development of these agents and their
      appropriate application in metastatic renal cell carcinoma, such as timing of
      therapy, choice of initial therapy, continued role of debulking nephrectomy and
      toxicity concerns. These issues are discussed in light of current data and
      strategies for further drug development are presented.

PMID- 17181490
TI  - Targeted therapies in metastatic renal cell carcinoma: the light at the end of
      the tunnel.
AB  - The year 2006 will mark a turning point in the daily management of patients with
      metastatic renal cell carcinoma. The impact of immunotherapy with interferon
      alpha or interleukin-2 has been shown to be restricted to a minority of patients.
      The growing understanding of molecular mechanisms involved in the pathogenesis of
      the disease, especially clear-cell carcinoma, has led to the development of
      multiple targeted therapies with significant clinical benefits. Two compounds
      that predominantly inhibit the tyrosine kinase activity of the vascular
      endothelial growth factor receptor have been shown to improve the progression
      free survival of patients in first- (sunitinib versus interferon-alpha) or second
      line (sorafenib versus placebo) treatment. Temsirolimus, an agent that inhibits
      the serine-threonine kinase activity of the mammalian target of rapamycin, offers
      better overall survival than interferon in patients with poor-risk
      characteristics. Further studies are needed to determine the optimal combinations
      of these agents in metastatic disease and to assess their impact in the adjuvant
      setting.

PMID- 17181491
TI  - Immunotherapy of multiple myeloma: the start of a long and tortuous journey.
AB  - The field of tumor immunotherapy is still in its infancy. It is becoming clear
      that the human immune response is the result of highly complex, continuously
      evolving interactions between cells of the adaptive and innate arms of the immune
      system, the internal and external environments, and normal and abnormal cells
      (e.g., myeloma plasma cells). Despite the considerable advances in our knowledge
      over the past 30 years, we have still only scratched the surface of the immune
      system's interaction with malignant diseases such as myeloma and to date, this
      has not translated into significantly better outcomes for patients with this
      disease. This review will summarize our current knowledge of the fundamental
      immunology of myeloma, review immunotherapy trials reported to date and discuss
      whether, in light of the current information, immunotherapy of multiple myeloma
      is an achievable goal.

PMID- 17181492
TI  - Role of immunochemotherapy in the treatment of chronic lymphocytic leukemia.
AB  - Major advances have been made in our understanding of the biology and
      opportunities for treatment of chronic lymphocytic leukemia in recent times.
      Newer treatment regimens incorporating purine nucleoside analogs have increased
      the rate of successful remission induction in chronic lymphocytic leukemia
      patients. Moreover, recent combination chemoimmunotherapy regimens have produced
      more frequent complete molecular remissions, and early evidence seems to suggest
      that this could result in prolonged duration of responses, although this
      association remains to be clearly demonstrated. This review will summarize recent
      advances in the biology and the management of chronic lymphocytic leukemia,
      including prognostic factors, pointing mainly on combination chemotherapy based
      on nucleoside analogs and monoclonal antibodies. In our opinion, in the future a
      significant improvement of clinical benefits in chronic lymphocytic leukemia will
      be obtained through the administration of cocktails of monoclonal antibodies
      combined with chemotherapy in different modalities.

PMID- 17181494
TI  - The ghost of George Bernard Shaw and Australian doctors' dilemmas.

PMID- 17181493
TI  - Hybrid adeno-associated virus bearing nonhomologous inverted terminal repeats
      enhances dual-vector reconstruction of minigenes in vivo.
AB  - We have previously demonstrated that hybrid adeno-associated viral (AAV) vectors
      bearing nonhomologous inverted terminal repeats (ITRs) enhance directional
      intermolecular recombination and the efficiency of dual-AAV vector trans-splicing
      in cultured cells. Using hybrid-ITR vectors carrying two exons of a lacZ
      minigene, we demonstrate that this dual-vector approach also mediates higher
      levels (3- to 6-fold) of gene reconstitution in mouse skeletal muscle, liver, and
      heart. Inhibition of the proteasome by systemic administration of Doxil (Food and
      Drug Administration-approved lipid-formulated doxorubicin) further enhanced dual
      vector trans-splicing 6- to 12-fold in two mouse strains. Hence, using hybrid-ITR
      AAV vectors in combination with proteasome modulation enhanced dual-vector
      delivery of a transgene approximately 36-fold over the current dual-vector trans
      splicing approaches. These data provide in vivo evidence that ITR sequence
      dependent homologous recombination, rather than nonhomologous end joining, is the
      predominant mechanism for AAV genome heterodimerization. Hence, enhanced
      directional recombination provided by hybrid-ITR vectors may be a useful in vivo
      strategy for improving dual-vector delivery of transgenes larger than the AAV
      packaging limit.

PMID- 17181495
TI  - Refugees in Australia: Changing faces, changing needs.

PMID- 17181496
TI  - Camp to clinic: A refugee journey.

PMID- 17181498
TI  - Barriers to access to health care for newly resettled sub-Saharan refugees in
      Australia.
AB  - OBJECTIVE: To determine barriers that affect access to health care for refugees
      from sub-Saharan Africa resettled in Sydney. DESIGN: Descriptive epidemiological
      study and survey. PARTICIPANTS AND SETTING: Parents of newly resettled refugee
      children seen at a tertiary hospital paediatric clinic between 10 June 2005 and
      19 May 2006. MAIN OUTCOME MEASURES: Socioeconomic indicators, health seeking
      behaviour, social barriers, and beliefs about health. RESULTS: Parents of 34 of a
      possible 35 families (97%) agreed to participate. Barriers to accessing health
      care include language barriers, financial handicap, lack of health information,
      not knowing where to seek help, and poor understanding of how to access health
      services. Most refugee families established connections with community and
      religious groups soon after arrival in Australia. CONCLUSIONS: Our findings
      suggest that most refugee families are not totally isolated in Australia, but
      form early connections with cultural, social and religious groups of their own
      ethnic background. These groups provide an opportunity to deliver health
      education and health information that would improve their access to health
      services.

PMID- 17181499
TI  - McCune-Albright syndrome.

PMID- 17181497
TI  - Community perceptions about infectious disease risk posed by new arrivals: A
      qualitative study.
AB  - OBJECTIVE: To report on perceptions about the risk of infectious diseases from
      new arrivals to Australia arising from a wider study of mothers' attitudes to
      childhood vaccination. DESIGN, PARTICIPANTS AND SETTING: Six focus groups on
      perceptions about the benefits and risks of vaccination with 37 mothers of
      children aged 5 weeks to 18 years, mostly conducted in middle-class areas of
      Sydney between 6 October and 15 December 1999. MAIN OUTCOME MEASURES: Mothers'
      views about infectious disease risk posed by immigration as a major reason to
      favour immunising children. RESULTS: The idea of immigration being the primary
      source of infectious diseases was striking, and arose among a number of
      participants in every group conversation. Mothers expressed their dread of new
      diseases "from overseas", and a sense that there are "more germs nowadays",
      mostly from increased immigration to Australia and international travel. Some
      perceived people coming from other countries as having more disease because of an
      innate susceptibility or through cultural practices. CONCLUSION: Recent media
      coverage about infectious diseases importation by African refugees not only
      feeds, but reflects, community concerns about new arrivals as a source of
      allegedly rampant infection threatening Australians. These concerns have little
      evidence base. Public health advocates need to be proactive with the media to
      provide sophisticated counter-messages that expose the underlying subtexts and
      educate the community about the true risks of infectious diseases.

PMID- 17181500
TI  - Outpatient treatment of malaria in recently arrived African migrants.
AB  - OBJECTIVE: To describe the clinical features and management of African migrants
      recently arrived in Western Australia and subsequently diagnosed with malaria.
      DESIGN, PARTICIPANTS AND SETTING: Retrospective case record analysis of African
      migrants aged > or = 16 years with malaria referred to Royal Perth Hospital (RPH)
      from the WA Migrant Health Unit (MHU) between 1 March 2003 and 30 September 2005.
      MAIN OUTCOME MEASURES: Demographic variables; clinical and laboratory variables;
      Plasmodium species; antimalarial medications used and their efficacy. RESULTS: 57
      (3.5%) of 1609 adult African migrants screened at the MHU were diagnosed with
      malaria and referred for treatment. 52 were infected with P. falciparum, two with
      P. ovale, one with P. malariae, and one with both P. falciparum and P. malariae;
      the malaria parasite could not be identified in one individual. No patients had
      severe malaria by World Health Organization criteria. Most patients (53/57) were
      treated as outpatients with oral antimalarial therapy; four patients without
      severe malaria were admitted to hospital for treatment and observation.
      Atovaquone-proguanil was the antimalarial medication most commonly used (in
      52/57), and treatment was well tolerated in most patients. Post-treatment follow
      up was possible in 50 patients; all 27 of those who were followed for 4 weeks or
      longer were cured. Cure could not be concluded in patients with shorter follow-up
      periods. All follow-up blood films were negative for malarial parasites.
      CONCLUSIONS: Outpatient treatment of malaria in recently arrived adult African
      migrants appeared to be safe and efficacious in our cohort.

PMID- 17181501
TI  - Health issues in newly arrived African refugees attending general practice
      clinics in Melbourne.
AB  - OBJECTIVE: To identify the most common health issues diagnosed by general
      practitioners in newly arrived African refugees. DESIGN: Descriptive study based
      on a purposive sample of six GPs to collate data from medical records of patients
      from African countries who had attended their clinics for the first time between
      1 January and 30 June 2005. SETTING: Two community health centres and two private
      general practices in metropolitan Melbourne. PARTICIPANTS: African refugee
      patients who arrived in Australia after 1 June 2004 and were seen by the six
      participating GPs between 1 January and 30 June 2005. MAIN OUTCOME MEASURES:
      Demographic characteristics, laboratory test results and final diagnoses.
      RESULTS: Data were collected from 258 patient files. Most patients were from
      Sudan (57%) or Liberia (17%). Half were aged under 15 years. The most common
      health problems identified were inadequate vaccinations, nutritional deficiencies
      (vitamin D and iron), infectious diseases (gastrointestinal infections,
      schistosomiasis, and latent tuberculosis) and dental disease. Musculoskeletal,
      psychological and social problems were common in adults. 37% of patients were
      tested for latent tuberculosis, and 25% of these tested positive. CONCLUSIONS:
      African refugees require comprehensive health assessments for undiagnosed and
      untreated health problems. While most of the common diseases identified are non
      communicable, if left untreated they will affect the long-term health and
      productivity of new settlers.

PMID- 17181502
TI  - Changing faces: A review of infectious disease screening of refugees by the
      Migrant Health Unit, Western Australia in 2003 and 2004.
AB  - OBJECTIVE: To document demographic characteristics and prevalence of infectious
      diseases in refugees and humanitarian entrants attending the Migrant Health Unit
      (MHU) in Perth for health assessment from 1 January 2003 to 31 December 2004.
      DESIGN: Retrospective case series. PARTICIPANTS: All refugees and humanitarian
      entrants arriving in Western Australia on subclass 200 and subclass 202 visas who
      were invited to attend the MHU. MAIN OUTCOME MEASURES: Demographic details,
      results of Mantoux tests, and blood and faecal tests for infectious diseases and
      parasites. RESULTS: WA accepted 2781 refugee and humanitarian entrants in 2003
      and 2004; 2617 were invited to attend the MHU, and 2111 (81%) actually attended
      for screening. Over three-quarters arrived from Africa. Overall, 25% had a
      positive Mantoux test result, 5% were carriers of hepatitis B, and 5% had
      positive serological test results for syphilis. People arriving from sub-Saharan
      Africa had the highest prevalence of most diseases, with 8% having malaria, 7%
      schistosomiasis, 5% hookworm, and 2% strongyloidiasis. CONCLUSION: Disease
      prevalence varied greatly between refugees from different countries and was
      particularly high in those arriving from sub-Saharan Africa, the origin of most
      of Australia's refugee and humanitarian entrants. These data support the need for
      refugees and humanitarian entrants from countries with high rates of disease to
      have access to a comprehensive postarrival medical assessment and appropriate
      follow-up health care. Health services must provide beneficial and cost-effective
      services that protect the health of both individual refugees and the wider
      community.

PMID- 17181504
TI  - Working to build a healthy Australia: A new era for the NHMRC.
AB  - The National Health and Medical Research Council Act 1992 (Cwlth) was amended in
      2006 to streamline governance arrangements and help the National Health and
      Medical Research Council (NHMRC) to become a more responsive organisation and
      more effective at both acquisition and implementation of new knowledge. As part
      of the NHMRC's plans for the future, we will implement the recommendations of the
      Investment Review of Health and Medical Research on policy- and practice-focused
      research, commercialisation, and recruitment of health and research professionals
      to the NHMRC. The NHMRC is also improving its process for selecting and
      supporting the best research across biomedical, clinical, public health and
      health services disciplines; and will develop, trial and introduce new forms of
      communicating evidence-based information.

PMID- 17181503
TI  - Severe Plasmodium falciparum malaria in refugee children despite reported
      predeparture antimalarial treatment.

PMID- 17181505
TI  - Research misconduct: Can Australia learn from the UK's stuttering system?
AB  - Research and publication misconduct is commoner than many believe, hard to detect
      and difficult to investigate, with institutions often being reluctant to take
      action. The first countries to set up formal systems for policing research
      misconduct were the United States and some Scandinavian countries. The US Office
      of Research Integrity (ORI) is a useful model for other countries; rather than
      conduct investigations, the ORI supervises the investigation by the respondent's
      institution. The United Kingdom has taken more than 10 years to set up a national
      supervisory body - the UK Panel for Research Integrity in Health and Biomedical
      Sciences. Unlike the ORI, it has no statutory basis. It is too early to tell
      whether the procedures set up in the UK will work. The present trend for
      governments to encourage universities to link up with industry may lead to a
      culture of secrecy and confused accountability. In any country, including
      Australia, intent on policing research, it is only possible for editors,
      reviewers or readers to initiate investigations, not undertake them, as power
      lies in the hands of employers, research funders and regulatory bodies.

PMID- 17181506
TI  - Australia needs an office of academic integrity.
AB  - Institutions investigating allegations of research misconduct are vulnerable to
      claims that their processes are inadequate or that they have an institutional
      conflict of interest. The Office of Research Integrity in the United States sets
      down standards for and reviews the adequacy of investigations of research
      misconduct by institutions; recognises that internal politics and the involvement
      of non-experts can lead to honest mistakes being regarded as serious misconduct;
      requires complainants and investigators to act "in good faith"; and reduces
      damaging publicity when complaints are misconceived or false. Australia needs an
      office of academic integrity to ensure that all complaints are thoroughly
      investigated; the investigative procedures meet international standards; fair
      processes are provided for complainants and respondents; and institutions are
      protected from claims of "cover-up" and institutional conflict of interest.

PMID- 17181507
TI  - Implementing a research governance framework for clinical and public health
      research.
AB  - Research conduct in Australia and worldwide is mostly unaudited. The purpose of
      good research governance is to ensure integrity in research through
      accountability, transparency and responsibility. Institutional responsibility for
      research governance has been adopted by Monash University's Department of
      Epidemiology and Preventive Medicine, providing clear lines of accountability for
      researchers as well as support and guidance. A research audit tool has been
      developed, identifying areas where practice could be improved especially among
      less experienced researchers; the most common adverse findings concerned research
      protocols and procedure manuals. The need for participant confidentiality,
      privacy and data security was found to be understood, and adhered to widely by
      all researchers. An evaluation of the effect of audit on researchers found that
      the process was well accepted.

PMID- 17181508
TI  - Preventing traffic accidents by mobile phone users.

PMID- 17181509
TI  - Phone use and crashes while driving: A representative survey of drivers in two
      Australian states.
AB  - OBJECTIVE: To explore the use and effects of using mobile phones while driving.
      DESIGN: Cross-sectional survey. SETTING: New South Wales and Western Australia,
      20 October to 7 November 2003. PARTICIPANTS: 1347 licensed drivers aged 18 to 65
      years. Data were weighted to reflect the corresponding driving population in each
      state. MAIN OUTCOME MEASURES: Mobile phone use while driving (hand-held, hands
      free and text messaging); adverse effects of use. RESULTS: While driving, an
      estimated 57.3% +/- 1.5% of drivers have ever used a mobile phone and 12.4% +/-
      1.0% have written text messages. Men, younger drivers and metropolitan residents
      were more likely to use a phone while driving and to report a higher frequency of
      use. Enforcement of hand-held phone restrictions was perceived to be low (69.0%
      +/- 1.5%) and an estimated 39.4% +/- 2.1% of people who phone while driving use a
      hand-held phone. Half of all drivers (50.1% +/- 1.6%) did not agree with
      extending the ban to include hands-free phones. Among drivers aged 18-65 years in
      NSW and WA, an estimated 45 800 +/- 16 466 (0.9% +/- 0.3%) have ever had a crash
      while using a mobile phone and, in the past year, 146 762 +/- 26 856 (3.0% +/-
      0.6%) have had to take evasive action to avoid a crash because of their phone
      use. CONCLUSIONS: Phone use while driving is prevalent and can result in adverse
      consequences, including crashes. Despite legislation, a significant proportion of
      drivers continue to use hand-held mobile phones while driving. Enhanced
      enforcement is needed.

PMID- 17181510
TI  - Assessing the wisdom of funding DrinkWise.

PMID- 17181511
TI  - Estimating the cost of alcohol-related absenteeism in the Australian workforce:
      The importance of consumption patterns.
AB  - OBJECTIVE: To estimate the extent and cost of alcohol-related absenteeism in the
      Australian workforce. DESIGN: A secondary analysis of select data obtained from
      13 582 Australian workers (aged > or = 14 years) collected as part of the 2001
      National Drug Strategy Household Survey. MAIN OUTCOME MEASURES: Self-reported
      measures of alcohol-related absenteeism, illness or injury absenteeism and
      alcohol consumption categorised according to National Health and Medical Research
      Council (NHMRC) guidelines for short- and long-term risk. RESULTS: The use of
      self-reported measures of alcohol-related absenteeism resulted in an estimate of
      2,682,865 work days lost due to alcohol use in 2001, at a cost of 437 million
      dollars. The use of self-reported measures of illness or injury absenteeism to
      determine the extent of absenteeism attributable to alcohol use resulted in an
      estimate of 7,402,341 work days lost, at a cost of 1 .2 billion dollars. These
      estimates are about 12 to 34 times greater than previous estimates based on
      national data. Low-risk drinkers and infrequent or occasional risky and high-risk
      drinkers accounted for 49%-66% of alcohol-related absenteeism. CONCLUSIONS: The
      extent and cost of alcohol-related absenteeism is far greater than previously
      reported, and more than half the burden of alcohol-related absenteeism is
      incurred by low-risk drinkers and those who infrequently drink heavily.

PMID- 17181512
TI  - The adventures of an alienist.

PMID- 17181513
TI  - The challenge of public health in Australia and the region.

PMID- 17181514
TI  - Solving the shortage of general practitioners in remote and rural Australia: A
      Sisyphean task?

PMID- 17181515
TI  - Rural and remote health in Australia: How to avert the deepening health care
      drought.

PMID- 17181516
TI  - Vegemite and chocolate sprinkles: Dutch medical students in rural Australia.
AB  - The Primary Health Care (PHC) working group of the Department of General Practice
      of Maastricht University in the Netherlands was founded in 1998 specifically to
      introduce students to patient care, research and education in primary health care
      settings outside the Netherlands. Rural health care in Australia is appealing to
      international medical students because of its unique setting. In the past 5
      years, 42 medical students from Maastricht University have pursued a medical
      elective in rural Australia, supervised by the PHC working group. Doctors and
      coordinators in primary care clinics across Australia have welcomed and
      supervised students from Maastricht and exposed them to the reality of rural
      health care. Future collaboration with other Australian primary care clinics is
      welcomed.

PMID- 17181517
TI  - Is Sir Astley Cooper's 1823 advice to medical students still relevant?
AB  - In an 1823 lecture to medical students on the principles and practice of surgery,
      London surgeon Sir Astley Cooper raised many issues still discussed among doctors
      today, including: the importance of studying anatomy; factors leading to what
      would now be called "adverse events"; and the possible legal consequences of
      making errors. Cooper stressed the need for open communication between doctors
      and patients. Cooper practised surgery during a period when old medical guild
      controls were breaking down and before new professional regulatory bodies had
      developed. Cooper's lecture suggests that the important principles that underpin
      competent, caring professional practice endure today.

PMID- 17181518
TI  - The possible causes of the pandemic of peptic ulcer in the late 19th and early
      20th century.
AB  - Helicobacter pylori is established as a cause of peptic ulcer (PU). Less well
      recognised is that an epidemic of PU began around the middle of the 19th century,
      reached a peak at the turn of the century, and is now on the wane. As the
      epidemic developed, the risk of PU increased in successive generations throughout
      life. Then the epidemic diminished in successive generations. The risk of gastric
      ulcer (GU) was highest in people born around 1885, while the risk of duodenal
      ulcer (DU) was highest in those born about 10-30 years later. H. pylori infection
      offers an inadequate explanation of the PU epidemic. Although the epidemic
      coincided with a major rise in cigarette smoking, PU then declined in spite of an
      increased incidence of smoking. None of the other possible causes of ulcer (non
      steroidal anti-inflammatory drugs, stress or diet) satisfactorily explains the
      epidemics of GU and DU and their asynchronicity. The best, but inadequate,
      explanation for the epidemic is the coincidence of the acquisition of a new
      potent strain of H. pylori in childhood and the uptake of smoking in adult life.

PMID- 17181519
TI  - The demise of professional courtesies: cui bono?

PMID- 17181520
TI  - Clinical paradigms revisited.

PMID- 17181521
TI  - The essence of the art of medicine.

PMID- 17181522
TI  - Should doctors appear in advertisments?

PMID- 17181523
TI  - Drug company sponsored symposia fulfil an important educational role.

PMID- 17181524
TI  - Disclosure needs to include the extent of a relationship.

PMID- 17181525
TI  - Don't regulate--abolish.

PMID- 17181527
TI  - Misleading title.

PMID- 17181529
TI  - A possible animal model of naturally occurring multinodular goitre in the
      Nilgiris of southern India.

PMID- 17181530
TI  - Medicine along the Mekong.

PMID- 17181531
TI  - Celebrity-based medicine.
AB  - OBJECTIVE: To collect contemporary accounts of celebrity use of complementary and
      alternative medicine (CAM), to aid clinicians in determining which CAM treatments
      patients are likely to use. DESIGN: Articles published during 2005 and 2006
      reporting celebrity use of CAM. RESULTS: 38 celebrities were found to use a wide
      range of CAM interventions. Homeopathy, acupuncture and Ayurveda were the most
      popular modalities. CONCLUSIONS: There may be many reasons why consumers use CAM,
      and wanting to imitate their idols is one of them.

PMID- 17181532
TI  - The repairing effect of a recombinant human connective-tissue growth factor in a
      burn-wounded rhesus-monkey (Macaca mulatta) model.
AB  - CTGF (connective-tissue growth factor) has been characterized as an extracellular
      matrix-associated protein that modulates basic-fibroblast-growth-factor
      signalling and angiogenesis. In the present paper, the cloning of the ctgf gene
      from human umbilical-vein endothelial cells and expression of the protein in
      Escherichia coli as an N-terminal hexahistidine fusion protein is described.
      Recombinant human CTGF (rhCTGF) was expressed and purified so that we could
      investigate its effect on the proliferation of human embryo fibroblast KMB-17 and
      NIH3T3 cells. The results indicated not only that the protein was properly
      folded, but also that it had the same specific activity and stability as the
      native protein. Furthermore, we administered this recombinant protein in a non
      human primate [rhesus monkey (Macaca mulatta)] burn-wound model and report the
      clinical findings and structural effects. Epitheliotrophic effects were
      conspicuous in wounded tissues at 10-100 ng of CTGF/cm(2), suggesting that
      administered rhCTGF can play a normal physiological role in wound repairing in a
      non-human primate model.

PMID- 17181534
TI  - Anesthesia for a child with giant axonal neuropathy.

PMID- 17181535
TI  - Remifentanil-induced mechanical responses and membrane potential changes in human
      umbilical arteries.
AB  - BACKGROUND: The aim of this study was to evaluate the characteristic features of
      the mechanical responses and membrane potential changes induced by remifentanil
      in human umbilical arteries (HUAs). The ionic mechanisms underlying the
      electrophysiological responses were pharmacologically assessed using two K(+)
      channel blockers. METHODS: Thirty-eight HUAs were obtained. Contraction
      relaxation, membrane potential changes and electrical responses of the HUAs were
      recorded. RESULTS: Remifentanil produced concentration-dependent relaxation in
      both endothelium-intact and endothelium-denuded HUA rings. Remifentanil produced
      a significantly greater relaxation response in intact than in denuded HUA rings.
      In endothelium-intact rings, pre-treatment with L-nitroarginine [N(w)-NITRO-(L)
      ARGININE (L-NO-ARG)] or indomethacin decreased the degree of remifentanil-induced
      relaxation. Remifentanil (10(-9)-10(-6) mol/l) produced a transient concentration
      dependent membrane hyperpolarization, which was not decreased by pre-treatment
      with L-NO-ARG or indomethacin. It also produced a small concentration-dependent
      hyperpolarization in the presence of charybdotoxin or tetraethylammonium.
      CONCLUSION: In both endothelium-intact and endothelium-denuded HUAs, remifentanil
      induces concentration-dependent vasorelaxation and simultaneously releases nitric
      oxide, prostaglandins and possibly an endothelium-derived hyperpolarizing factor.
      In addition, it produces hyperpolarization in a dose-dependent manner.
      Hyperpolarization induced by remifentanil involves the activation of Ca(2+)
      dependent and Ca(2+)-independent potassium channels regulated by intracellular
      Ca(2+).

PMID- 17181536
TI  - Therapeutic hypothermia after out-of-hospital cardiac arrest: experiences with
      patients treated with percutaneous coronary intervention and cardiogenic shock.
AB  - BACKGROUND: Therapeutic hypothermia has been shown to increase survival after out
      of-hospital cardiac arrest (OHCA). The trials documenting such benefit excluded
      patients with cardiogenic shock and only a few patients were treated with
      percutaneous coronary intervention prior to admission to an intensive care unit
      (ICU). We use therapeutic hypothermia whenever cardiac arrest patients do not
      wake up immediately after return of spontaneous circulation. METHODS: This paper
      reports the outcome of 50 OHCA patients with ventricular fibrillation admitted to
      a tertiary referral hospital for immediate coronary angiography and percutaneous
      coronary intervention when indicated. Patients were treated with intra-aortic
      balloon counterpulsation (IABP) (23 of 50 patients) if indicated. All patients
      who were still comatose were treated with therapeutic hypothermia at 32-34
      degrees C for 24 h before rewarming. The end-points were survival and cerebral
      performance category (CPC: 1, best; 5, dead) after 6 months. RESULTS: Forty-one
      patients (82%) survived until 6 months. Thirty-four patients (68%) were in CPC 1
      or 2, and seven (14%) were in CPC 3. Of the 23 patients treated with IABP, 14
      (61%) survived with CPC 1 or 2. In patients not treated with IABP, 20 patients
      (74%) survived with CPC 1 or 2. Forty patients (80%) developed myocardial
      infarction. Percutaneous coronary intervention was performed in 36 patients
      (72%). CONCLUSION: In OHCA survivors who reached our hospital, the survival rate
      was high and the neurological outcome acceptable. Our results indicate that the
      use of therapeutic hypothermia is justified even in haemodynamically unstable
      patients and those treated with percutaneous coronary intervention.

PMID- 17181533
TI  - Ca2+, NAD(P)H and membrane potential changes in pancreatic beta-cells by methyl
      succinate: comparison with glucose.
AB  - The present study was undertaken to determine the main metabolic secretory
      signals generated by the mitochondrial substrate MeS (methyl succinate) compared
      with glucose in mouse and rat islets and to understand the differences.
      Glycolysis and mitochondrial metabolism both have key roles in the stimulation of
      insulin secretion by glucose. Both fuels elicited comparable oscillatory patterns
      of Ca2+ and changes in plasma and mitochondrial membrane potential in rat islet
      cells and clonal pancreatic beta-cells (INS-1). Saturation of the Ca2+ signal
      occurred between 5 and 6 mM MeS, while secretion reached its maximum at 15 mM,
      suggesting operation of a K(ATP)-channel-independent pathway. Additional
      responses to MeS and glucose included elevated NAD(P)H autofluorescence in INS-1
      cells and islets and increases in assayed NADH and NADPH and the ATP/ADP ratio.
      Increased NADPH and ATP/ADP ratios occurred more rapidly with MeS, although
      similar levels were reached after 5 min of exposure to each fuel, whereas NADH
      increased more with MeS than with glucose. Reversal of MeS-induced cell
      depolarization by Methylene Blue completely inhibited MeS-stimulated secretion,
      whereas basal secretion and KCl-induced changes in these parameters were not
      affected. MeS had no effect on secretion or signals in the mouse islets, in
      contrast with glucose, possibly due to a lack of malic enzyme. The data are
      consistent with the common intermediates being pyruvate, cytosolic NADPH or both,
      and suggest that cytosolic NADPH production could account for the more rapid
      onset of MeS-induced secretion compared with glucose stimulation.

PMID- 17181537
TI  - Tracheal shortening during laparoscopic gynecologic surgery.
AB  - BACKGROUND: During laparoscopic gynecologic surgery, pneumoperitoneum combined
      with the Trendelenburg position moves the carina towards the tip of the
      endotracheal tube (ETT), decreasing the margin of safety for the ETT position and
      increasing accidental endobronchial intubation. However, it remains to be
      established whether the tracheal length itself is actually changed. We conducted
      a prospective observational study to measure the change in the length of the
      trachea and the distance between the ETT tip and the carina in patients
      undergoing gynecologic laparoscopic surgery. METHODS: Twenty-three patients
      scheduled for laparoscopic gynecologic surgery were enrolled. In the neutral
      position, the tracheal length was measured using a fiberoptic bronchoscope. The
      distance between the ETT tip and the carina was also measured. The tracheal
      length and the distance between the ETT tip and the carina were measured again 10
      min after carbon dioxide (CO(2)) pneumoperitoneum (12-14 mmHg) combined with the
      Trendelenburg position (15 degrees ). RESULTS: In the neutral position, the
      tracheal length was 11.09 +/- 0.90 cm and the distance between the ETT tip and
      the carina was 3.36 +/- 1.04 cm. After pneumoperitoneum combined with the
      Trendelenburg position, the distance between the ETT tip and the carina had
      decreased by 0.85 +/- 0.28 cm. The tracheal length had also decreased by 0.42 +/-
      0.19 cm, which was equivalent to 49.7% of the decrease in the distance between
      the ETT tip and the carina. CONCLUSIONS: These results suggest that tracheal
      shortening may contribute to a decrease in the distance between the ETT tip and
      the carina, increasing the risk of accidental endobronchial intubation during
      laparoscopic gynecologic surgery.

PMID- 17181540
TI  - Kinetics of electron transfer from NADH to the Escherichia coli nitric oxide
      reductase flavorubredoxin.
AB  - Escherichia coli flavorubredoxin (FlRd) belongs to the family of flavodiiron
      proteins (FDPs), microbial enzymes that are expressed to scavenge nitric oxide
      (NO) under anaerobic conditions. To degrade NO, FlRd has to be reduced by NADH
      via the FAD-binding protein flavorubredoxin reductase, thus the kinetics of
      electron transfer along this pathway was investigated by stopped-flow absorption
      spectroscopy. We found that NADH, but not NADPH, quickly reduces the FlRd
      reductase (k = 5.5 +/- 2.2 x 10(6) M(-1).s(-1) at 5 degrees C), with a limiting
      rate of 255 +/- 17 s(-1). The reductase in turn quickly reduces the rubredoxin
      (Rd) center of FlRd, as assessed at 5 degrees C working with the native FlRd
      enzyme (k = 2.4 +/- 0.1 x 10(6) m(-1).s(-1)) and with its isolated Rd-domain (k
      approximately 1 x 10(7) M(-1).s(-1)); in both cases the reaction was found to be
      dependent on pH and ionic strength. In FlRd the fast reduction of the Rd center
      occurs synchronously with the formation of flavin mononucleotide semiquinone. Our
      data provide evidence that (a) FlRd-reductase rapidly shuttles electrons between
      NADH and FlRd, a prerequisite for NO reduction in this detoxification pathway,
      and (b) the electron accepting site in FlRd, the Rd center, is in very fast redox
      equilibrium with the flavin mononucleotide.

PMID- 17181539
TI  - Protein disulfide isomerase family proteins involved in soybean protein
      biogenesis.
AB  - Protein disulfide isomerase family proteins are known to play important roles in
      the folding of nascent polypeptides and the formation of disulfide bonds in the
      endoplasmic reticulum. In this study, we cloned two similar protein disulfide
      isomerase family genes from soybean leaf (Glycine max L. Merrill cv. Jack) mRNA
      by RT-PCR using forward and reverse primers designed from the expressed sequence
      tag clone sequences. The cDNA encodes a protein of either 364 or 362 amino acids,
      named GmPDIS-1 or GmPDIS-2, respectively. The nucleotide and amino acid sequence
      identities of GmPDIS-1 and GmPDIS-2 were 68% and 74%, respectively. Both proteins
      lack the C-terminal, endoplasmic reticulum-retrieval signal, KDEL. Recombinant
      proteins of both GmPDIS-1 and GmPDIS-2 were expressed in Escherichia coli as
      soluble folded proteins that showed both an oxidative refolding activity of
      denatured ribonuclease A and a chaperone activity. Their domain structures were
      identified as containing two thioredoxin-like domains, a and a', and an ERp29c
      domain by peptide mapping with either trypsin or V8 protease. In cotyledon cells,
      both proteins were shown to distribute to the endoplasmic reticulum and protein
      storage vacuoles by confocal microscopy. Data from coimmunoprecipitation and
      crosslinking experiments suggested that GmPDIS-1 associates with proglycinin, a
      precursor of the seed storage protein glycinin, in the cotyledon. Levels of
      GmPDIS-1, but not of GmPDIS-2, were increased in cotyledons, where glycinin
      accumulates during seed development. GmPDIS-1, but not GmPDIS-2, was induced
      under endoplasmic reticulum-stress conditions.

PMID- 17181541
TI  - Diversification of the insulin receptor family in the helminth parasite
      Schistosoma mansoni.
AB  - Insulin signalling is a very ancient and well conserved pathway in metazoan
      cells, dependent on insulin receptors (IR) which are transmembrane proteins with
      tyrosine kinase activity. A unique IR is usually present in invertebrates whereas
      two IR members are found with different functions in vertebrates. This work
      demonstrates the existence of two distinct IR homologs (SmIR-1 and SmIR-2) in the
      parasite trematode Schistosoma mansoni. These two receptors display differences
      in several structural motifs essential for signalling and are differentially
      expressed in parasite tissues, suggesting that they could have distinct
      functions. The gene organization of SmIR-1 and SmIR-2 is similar to that of the
      human IR and to that of the IR homolog from Echinococcus multilocularis (EmIR),
      another parasitic platyhelminth. SmIR-1 and SmIR-2 were shown to interact with
      human pro-insulin but not with pro-insulin-like growth factor-1 in two-hybrid
      assays. Phylogenetic results indicated that SmIR-2 and EmIR might be functional
      orthologs whereas SmIR-1 would have emerged to fulfil specific functions in
      schistosomes.

PMID- 17181538
TI  - N-glycans of the porcine nematode parasite Ascaris suum are modified with
      phosphorylcholine and core fucose residues.
AB  - In recent years, the glycoconjugates of many parasitic nematodes have attracted
      interest due to their immunogenic and immunomodulatory nature. Previous studies
      with the porcine roundworm parasite Ascaris suum have focused on its
      glycosphingolipids, which were found, in part, to be modified by
      phosphorylcholine. Using mass spectrometry and western blotting, we have now
      analyzed the peptide N-glycosidase A-released N-glycans of adults of this
      species. The presence of hybrid bi- and triantennary N-glycans, some modified by
      core alpha1,6-fucose and peripheral phosphorylcholine, was demonstrated by
      LC/electrospray ionization (ESI)-Q-TOF-MS/MS, as was the presence of
      paucimannosidic N-glycans, some of which carry core alpha1,3-fucose, and
      oligomannosidic oligosaccharides. Western blotting verified the presence of
      protein-bound phosphorylcholine and core alpha1,3-fucose, whereas
      glycosyltransferase assays showed the presence of core alpha1,6
      fucosyltransferase and Lewis-type alpha1,3-fucosyltransferase activities.
      Although, the unusual tri- and tetrafucosylated glycans found in the model
      nematode Caenorhabditis elegans were not found, the vast majority of the N
      glycans found in A. suum represent a subset of those found in C. elegans; thus,
      our data demonstrate that the latter is an interesting glycobiological model for
      parasitic nematodes.

PMID- 17181542
TI  - S-Layers as a basic building block in a molecular construction kit.
AB  - Crystalline arrays of protein or glycoprotein subunits forming surface layers (S
      layers) are the most common outermost envelope components of prokaryotic
      organisms (archaea and bacteria). The wealth of information on the structure,
      chemistry, genetics, morphogenesis, and function of S-layers has revealed a broad
      application potential. As S-layers are periodic structures, they exhibit
      identical physicochemical properties for each molecular unit down to the
      subnanometer level and possess pores of identical size and morphology. Many
      applications of S-layers in nanobiotechnology depend on the ability of isolated
      subunits to recrystallize into monomolecular lattices in suspension or on
      suitable surfaces and interfaces. S-Layer lattices can be exploited as
      scaffolding and patterning elements for generating more complex supramolecular
      assemblies and structures, as required for life and nonlife science applications.

PMID- 17181543
TI  - Nanoparticle-enzyme hybrid systems for nanobiotechnology.
AB  - Biomolecule-nanoparticle (NP) [or quantum-dot (QD)] hybrid systems combine the
      recognition and biocatalytic properties of biomolecules with the unique
      electronic, optical, and catalytic features of NPs and yield composite materials
      with new functionalities. The biomolecule-NP hybrid systems allow the development
      of new biosensors, the synthesis of metallic nanowires, and the fabrication of
      nanostructured patterns of metallic or magnetic NPs on surfaces. These advances
      in nanobiotechnology are exemplified by the development of amperometric glucose
      sensors by the electrical contacting of redox enzymes by means of AuNPs, and the
      design of an optical glucose sensor by the biocatalytic growth of AuNPs. The
      biocatalytic growth of metallic NPs is used to fabricate Au and Ag nanowires on
      surfaces. The fluorescence properties of semiconductor QDs are used to develop
      competitive maltose biosensors and to probe the biocatalytic functions of
      proteases. Similarly, semiconductor NPs, associated with electrodes, are used to
      photoactivate bioelectrocatalytic cascades while generating photocurrents.

PMID- 17181544
TI  - Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene
      implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID)
      in Somalia and a single, common haplotype indicates common ancestry.
AB  - Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that
      causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in
      the majority of cases to a less severe form in a small minority of patients. Five
      patients of Somali origin from four unrelated families, with severe ADA-SCID,
      were registered in the Greater London area. Patients and their parents were
      investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations
      K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3'
      end of an Alu element (AluVpA) positioned 1.1 kb upstream of the ADA
      transcription start site. All patients were homozygous for the haplotype ADA
      7T/ADA-239G/ADA-425G/AluVpA7. Among 207 Somali immigrants to Denmark, the
      frequency of ADA c7C>T and the maximum likelihood estimate of the frequency of
      the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7 were both 0.012 (carrier frequency
      2.4%). Based on the analysis of AluVpA alleles, the ADA c7C/T mutation was
      estimated to be approximately 7,100 years old. Approximately 1 out of 5 - 10000
      Somali children will be born with ADA deficiency due to an ADA c7C/T mutation,
      although within certain clans the frequency may be significantly higher. ADA-SCID
      may be a frequent immunodeficiency disorder in Somalia, but will be
      underdiagnosed due to the prevailing socioeconomic and nutritional deprivation.

PMID- 17181545
TI  - The relationship between CAG repeat length and age of onset differs for
      Huntington's disease patients with juvenile onset or adult onset.
AB  - Age of onset for Huntington's disease (HD) varies inversely with the length of
      the disease-causing CAG repeat expansion in the HD gene. A simple exponential
      regression model yielded adjusted R-squared values of 0.728 in a large set of
      Venezuelan kindreds and 0.642 in a North American, European, and Australian
      sample (the HD MAPS cohort). We present evidence that a two-segment exponential
      regression curve provides a significantly better fit than the simple exponential
      regression. A plot of natural log-transformed age of onset against CAG repeat
      length reveals this segmental relationship. This two-segment exponential
      regression on age of onset data increases the adjusted R-squared values by 0.012
      in the Venezuelan kindreds and by 0.035 in the HD MAPS cohort. Although the
      amount of additional variance explained by the segmental regression approach is
      modest, the two slopes of the two-segment regression are significantly different
      from each other in both the Venezuelan kindreds [F(2, 439) = 11.13, P= 2 x 10(
      5)] and in the HD MAPS cohort [F(2, 688) = 38.27, P= 2 x 10(-16)]. In both
      populations, the influence of each CAG repeat on age of onset appears to be
      stronger in the adult-onset range of CAG repeats than in the juvenile-onset
      range.

PMID- 17181546
TI  - Use of biomolecular templates for the fabrication of metal nanowires.
AB  - The nano-scale spatial organization of metallic and other inorganic materials
      into 1D objects is a key task in nanotechnology. Nano-scale fibers and tubes are
      very useful templates for such organization because of their inherent 1D
      organization. Fibrillar biological molecules and biomolecular assemblies are
      excellent physical supports on which to organize the inorganic material.
      Furthermore, these biological assemblies can facilitate high-order organization
      and specific orientation of inorganic structures by their utilization of highly
      specific biological recognition properties. In this minireview, I will describe
      the use of biomolecules and biomolecular assemblies, including DNA, proteins,
      peptides, and even viral particles, which are excellent templates for 1D
      organization of inorganic materials into wires. This ranges from simple attempts
      at electroless deposition on inert biological templates to the advanced use of
      structural motifs and specific protein-DNA interactions for nano-bio-lithography
      as well as the fabrication of multilayer organic and inorganic composites. The
      potential technological applications of these hybrid biological-inorganic
      assemblies will be discussed.

PMID- 17181547
TI  - Electrochemical biosensing with nanoparticles.
AB  - This minireview looks at the latest trends in the use of nanoparticles (NPs) in
      electrochemical biosensing systems. It includes electrochemical characterization
      of NPs for use as labels in affinity biosensors and other applications. DNA
      analysis involving NPs is one of the most important topics of current research in
      bionanotechnology. The advantages of the use of NPs in designing novel
      electrochemical sensors for DNA analysis are reviewed. Electrochemical NPs can
      also be used in designing immunoassays, offering the possibility of easy, low
      cost and simultaneous detection of several proteins. Research into NP
      applications in electrochemical analysis is in its infancy. Several aspects
      related to sensitivity as well integration of all the assay steps into a single
      one need to be improved.

PMID- 17181549
TI  - Role of peroxynitrite in secondary oxidative damage after spinal cord injury.
AB  - Peroxynitrite (PON, ONOO(-)), formed by nitric oxide synthase-generated nitric
      oxide radical ( NO) and superoxide radical (O(2) (-)), is a crucial player in
      post-traumatic oxidative damage. In the present study, we determined the spatial
      and temporal characteristics of PON-derived oxidative damage after a moderate
      contusion injury in rats. Our results showed that 3-nitrotyrosine (3-NT), a
      specific marker for PON, rapidly accumulated at early time points (1 and 3 h) and
      a significant increase compared with sham rats was sustained to 1 week after
      injury. Additionally, there was a coincident and maintained increase in the
      levels of protein oxidation-related protein carbonyl and lipid peroxidation
      derived 4-hydroxynonenal (4-HNE). The peak increases of 3-NT and 4-HNE were
      observed at 24 h post-injury. In our immunohistochemical results, the co
      localization of 3-NT and 4-HNE results indicates that PON is involved in lipid
      peroxidative as well as protein nitrative damage. One of the consequences of
      oxidative damage is an exacerbation of intracellular calcium overload, which
      activates the cysteine protease calpain leading to the degradation of several
      cellular targets including cytoskeletal protein (alpha-spectrin). Western blot
      analysis of alpha-spectrin breakdown products showed that the 145-kDa fragments
      of alpha-spectrin, which are specifically generated by calpain, were
      significantly increased as soon as 1 h following injury although the peak
      increase did not occur until 72 h post-injury. The later activation of calpain is
      most likely linked to PON-mediated secondary oxidative impairment of calcium
      homeostasis. Scavengers of PON, or its derived free radical species, may provide
      an improved antioxidant neuroprotective approach for the treatment of post
      traumatic oxidative damage in the injured spinal cord.

PMID- 17181550
TI  - Bone morphogenetic protein down-regulation of neuronal pituitary adenylate
      cyclase-activating polypeptide and reciprocal effects on vasoactive intestinal
      peptide expression.
AB  - Among bone morphogenetic proteins (BMPs), the decapentaplegic (Dpp; BMP2, BMP4)
      and glass bottom boat (Gbb/60A; BMP5, BMP6, BMP7) subgroups have well-described
      functions guiding autonomic and sensory neuronal development, fiber formation and
      neurophenotypic identities. Evaluation of rat superior cervical ganglia (SCG)
      post-ganglionic sympathetic neuron developmental regulators identified that
      selected BMPs of the transforming growth factor beta superfamily have reciprocal
      effects on neuronal pituitary adenylate cyclase-activating polypeptide (PACAP)
      and vasoactive intestinal peptide (VIP) expression. Dpp and Gbb/60A BMPs rapidly
      down-regulated PACAP expression, while up-regulating other sympathetic
      neuropeptides, including PACAP-related VIP. The suppressive effects of BMP on
      PACAP mRNA and peptide expression were potent, efficacious and phosphorylated
      mothers against decapentaplegic homolog (Smad) signaling-dependent. Axotomy of
      SCG dramatically increases PACAP expression, and the possibility that abrogation
      of inhibitory retrograde target tissue BMP signaling may contribute to this up
      regulation of sympathetic neuron PACAP was investigated. Replacement of BMP6 to
      SCG explant preparations significantly blunted the injury-induced elevated PACAP
      expression, with a concomitant decrease in sympathetic PACAP-immunoreactive
      neuron numbers. These studies suggested that BMPs modulate neuropeptide identity
      and diversity by stimulating or restricting the expression of specific
      peptidergic systems. Furthermore, the liberation of SCG neurons from target
      derived BMP inhibition following axotomy may be one participating mechanism
      associated with injury-induced neuropeptidergic plasticity.

PMID- 17181551
TI  - Characterization of wild-type and mutant forms of human tryptophan hydroxylase 2.
AB  - Tryptophan hydroxylase (TPH) catalyses the rate-limiting step in the biosynthesis
      of serotonin. In vertebrates, the homologous genes tph1 and tph2 encode two
      different enzymes with distinct patterns of expression, enzyme kinetics and
      regulation. Variants of TPH2 have recently reported to be associated with reduced
      serotonin production and behavioural alterations in man and mice. We have
      produced the human forms of these enzymes in Esherichia coli and in human
      embryonic kidney cell lines (HEK293) and examined the effects of mutations on
      their heterologous expression levels, solubility, thermal stability, secondary
      structure, and catalytic properties. Pure human TPH2 P449R (corresponds to mouse
      P447R) had comparable catalytic activity (V(max)) and solubility relative to the
      wild type, but had decreased thermal stability; whereas human TPH2 R441H had
      decreased activity, solubility and stability. Thus, we consider the variations in
      kinetic values between wild-type and TPH2 mutants to be of secondary importance
      to their effects on protein stability and solubility. These findings provide
      potential molecular explanations for disorders related to the central
      serotonergic system, such as depression or suicidal behaviour.

PMID- 17181552
TI  - Arachidonic acid potentiates exocytosis and allows neuronal SNARE complex to
      interact with Munc18a.
AB  - Neuronal communication relies on the fusion of neurotransmitter-containing
      vesicles with the neuronal plasma membrane. Recent genetic studies have
      highlighted the critical role played by polyunsaturated fatty acids in
      neurotransmission, however, there is little information available about which
      fatty acids act on exocytosis and, more importantly, by what mechanism. We have
      used permeabilized chromaffin cells to screen various fatty acids of the n-3 and
      n-6 series for their acute effects on exocytosis. We have demonstrated that an n
      6 series polyunsaturated fatty acid, arachidonic acid, potentiates secretion from
      intact neurosecretory cells regardless of the secretagogue used. We have shown
      that arachidonic acid dose dependently increases soluble NSF attachment protein
      receptor complex formation in chromaffin cells and bovine cortical brain extracts
      and that a non-hydrolysable analogue of arachidonic acid causes a similar
      increase in SNARE complex formation. This prompted us to examine the effect of
      arachidonic acid on SNARE protein interactions with Munc18a, a protein known to
      prevent Syntaxin1a engagement into the SNARE complex in vitro. In the presence of
      arachidonic acid, we show that Munc18a can interact with the neuronal SNARE
      complex in a dose-dependent manner. We further demonstrate that arachidonic acid
      directly interacts with Syntaxin1a.

PMID- 17181553
TI  - Fibroblast growth factor receptor 3 kinase domain mutation increases cortical
      progenitor proliferation via mitogen-activated protein kinase activation.
AB  - We have previously shown that mice carrying the K644E kinase domain mutation in
      fibroblast growth factor receptor 3 (Fgfr3) (EIIa;Fgfr3(+/K644E)) have enlarged
      brains with increased proliferation and decreased apoptosis of the cortical
      progenitors. Despite its unique rostral-low caudal-high gradient expression in
      the cortex, how Fgfr3 temporally and spatially influences progenitor
      proliferation is unknown. In vivo BrdU labelling now showed that progenitor
      proliferation was 10-46% higher in the EIIa;Fgfr3(+/K644E) cortex compared with
      wild type during embryonic day 11.5 (E11.5)-E13.5. The difference in
      proliferation between the EIIa;Fgfr3(+/K644E) and wild-type cortices was the
      greatest in the caudal cortex at E12.5 and E13.5. Inhibition of mitogen-activated
      or extracellular signal-regulated protein kinase (MEK) in vitro at E11.5 reduced
      the proliferation rate of the EIIa;Fgfr3(+/K644E) cortical progenitors to similar
      levels observed in the wild type, indicating that the majority of the increase in
      cell proliferation caused by the Fgfr3 mutation is mitogen-activated protein
      kinase (MAPK) pathway-dependent at this stage. In addition, elevated levels of
      Sprouty were observed in the EIIa;Fgfr3(+/K644E) telencephalon at E14.5,
      indicating the presence of negative feedback that may have suppressed further
      MAPK activation. We suggest that temporal activation of MAPK is largely
      responsible for cell proliferation caused by the Fgfr3 mutation during early
      stages of cortical development.

PMID- 17181554
TI  - Overexpression of midkine contributes to anti-apoptotic effects in human
      meningiomas.
AB  - Meningiomas are the second most common intracranial tumours. Most meningiomas
      grow slowly; however, atypical and anaplastic meningiomas show an aggressive
      biological behaviour. Overexpression of growth factors is considered to be a
      cause of carcinogenesis. Midkine and pleiotrophin are heparin-binding growth
      factors that promote growth, survival, migration and differentiation of various
      target cells. Both molecules are highly expressed during human embryogenesis but
      are rarely seen in the adult. We show that in relation to normal dura and
      arachnoid tissues, midkine was overexpressed in meningiomas on the mRNA and
      protein level, whereas pleiotrophin was not. Thereby, not only the intact but
      also the truncated form of midkine could be observed. The expression of midkine
      receptors was variable in different samples. Midkine stimulation of cultured
      meningioma cells induced phosphorylation of Akt, whereas no increase in
      phosphorylation of p42/44 MAPK or p38 MAPK could be detected. Midkine did not
      influence the proliferation of meningioma cells in vitro, but it did protect
      meningioma cells from camptothecin-mediated apoptotic cell death through
      reduction in the amounts of active caspase-3. These findings provide evidence for
      the overexpression of midkine in meningiomas which contributes to protection from
      cell death in these second most common intracranial tumours.

PMID- 17181555
TI  - Differential coupling of alpha7 and non-alpha7 nicotinic acetylcholine receptors
      to calcium-induced calcium release and voltage-operated calcium channels in PC12
      cells.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation
      channels that can modulate various neuronal processes by altering intracellular
      Ca(2+) levels. Following nAChR stimulation Ca(2+) can enter cells either
      directly, through the intrinsic ion channel, or indirectly following voltage
      operated Ca(2+) channel (VOCC) activation; Ca(2+) levels can subsequently be
      amplified via Ca(2+)-induced Ca(2+) release from intracellular stores. We have
      used subtype-selective nAChR agonists to investigate the Ca(2+) sources
      contributing to alpha7 and non-alpha7 nAChR-mediated increases in intracellular
      Ca(2+) in PC12 cells. Application of the alpha7 nAChR positive allosteric
      modulator PNU 120596 (10 mum), in conjunction with the alpha7 nAChR agonist,
      compound A [(R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2
      carboxamide), 10 nm], produces a rapid increase in fluo-3 fluorescence that is
      prevented by the selective alpha7 nAChR antagonist alpha-bungarotoxin. The non
      alpha7 nAChR agonist 5-Iodo-A-85380 produces alpha-bungarotoxin-insensitive
      increases in intracellular Ca(2+) (EC(50) = 11.2 mum). Using these selective
      agonists or KCl in conjunction with general and selective VOCC inhibitors, we
      demonstrate that the primary route of Ca(2+) entry following either non-alpha7
      nAChR activation or KCl stimulation is via L-type VOCCs. In contrast, the alpha7
      nAChR-mediated response is unaffected by VOCC blockers but is inhibited by
      modulators of intracellular Ca(2+) stores. These results indicate that alpha7 and
      non-alpha7 nAChRs are differentially coupled to Ca(2+)-induced Ca(2+) release and
      VOCCs, respectively.

PMID- 17181556
TI  - CCR7, CCR8, CCR9 and CCR10 in the mouse hippocampal CA1 area and the dentate
      gyrus during and after pilocarpine-induced status epilepticus.
AB  - The present study showed CCR7, CCR8, CCR9 and CCR10 in the normal Swiss mouse
      hippocampus at both protein and mRNA levels. CCR7, CCR9 and CCR10 were mainly
      localized in hippocampal principal cells and some interneurons. CCR9 was also
      found in the mossy fibres and/or terminals, suggesting an axonal or presynaptic
      localization, and CCR10 in apical dendrites of pyramidal neurons in the CA1 area.
      CCR8 was observed in interneurons. Double-labelling immunocytochemistry revealed
      that most of calbindin (CB)-, calretinin (CR)- and parvalbumin (PV)
      immunopositive neurons expressed CCR7-10, except CR-immunopositive cells in which
      only 10 to 12% expressed CCR8. During and after pilocarpine-induced status
      epilepticus, progressive changes of each of CCR7, CCR8, CCR9 and CCR10 proteins
      occurred in different patterns at various time points. Sensitive real-time PCR
      showed similar change patterns at mRNA level. At the chronic stage, i.e. at 2
      months after pilocarpine-induced status epilepticus, significant reduction of
      CCR7-10 expression in CB-, CR- and PV-immunpositive interneurons may suggest the
      phenotype change of surviving interneurons. Double labelling of CCR7, CCR8 and
      CCR9 with glial fibrillary acidic protein (GFAP) at the chronic stage may suggest
      an induced expression in reactive astrocytes. The present study may, therefore,
      for the first time, provide evidence that CCR7-10 may be involved in normal
      hippocampal activity. The demonstration of the progressive changes of CCR7-10
      during and after status epilepticus may open a new area to reveal the mechanism
      of neuronal loss after status epilepticus and of epileptogenesis.

PMID- 17181557
TI  - Immune tolerance and control of CNS autoimmunity: from animal models to MS
      patients.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease resulting in
      demyelination and axonal loss within the CNS. An autoimmune reaction directed
      against myelin antigens contributes to the disease process. As the CNS has long
      been considered an immune privileged site, how such an immune response can
      develop locally has remained enigmatic. Recent data, mostly based on the study of
      animal models for MS, have shown that the CNS is in fact more permissive to the
      development of immune responses than previously thought. This observation is
      counterbalanced by the fact that immune tolerance to myelin antigens can be
      induced outside the CNS. This review focuses on the mechanisms preventing CNS
      autoimmunity, which act in three separate tissues. In the thymus, expression of
      CNS autoantigens promotes partial protection, notably through elimination of
      autoreactive T cells. In the secondary lymphoid organs, the remaining
      autoreactive T cells are kept under control by the naturally occurring regulatory
      T cells of the CD4(+)Foxp3(+) phenotype. In the CNS, multiple mechanisms
      including the local activation of regulatory T cells further limit autoimmunity.
      A better understanding of the induction of regulatory T cells, of their
      mechanisms of action, and of approaches to manipulate them in vivo may offer new
      therapeutic opportunities for MS patients.

PMID- 17181558
TI  - In vivo analysis of serotonin clearance in rat hippocampus reveals that repeated
      administration of p-methoxyamphetamine (PMA), but not 3,4
      methylenedioxymethamphetamine (MDMA), leads to long-lasting deficits in serotonin
      transporter function.
AB  - p-Methoxyamphetamine (PMA) has been implicated in fatalities as a result of
      'ecstasy' (MDMA) overdose worldwide. Like MDMA, acute effects are associated with
      marked changes in serotonergic neurotransmission, but the long-term effects of
      PMA are poorly understood. The aim of this study was to determine the effect of
      repeated PMA administration on in vitro measures of neurodegeneration: serotonin
      (5-HT) uptake, 5-HT transporter (SERT) density and 5-HT content in the
      hippocampus, and compare with effects on in vivo 5-HT clearance. Male rats
      received PMA, MDMA (4 or 15 mg/kg s.c., twice daily) or vehicle for 4 days and 2
      weeks later indices of SERT function were measured. [(3)H]5-HT uptake into
      synaptosomes and [(3)H]cyanoimipramine binding to the SERT were significantly
      reduced by both PMA and MDMA treatments. 5-HT content was reduced in MDMA-, but
      not PMA-treatment. In contrast, clearance of locally applied 5-HT measured in
      vivo by chronoamperometry was only reduced in rats treated with 15 mg/kg PMA. The
      finding that 5-HT clearance in vivo was unaltered by MDMA treatment suggests that
      in vitro measures of 5-HT axonal degeneration do not necessarily predict
      potential compensatory mechanisms that maintain SERT function under basal
      conditions.

PMID- 17181559
TI  - Tropisetron modulation of the glycine receptor: femtomolar potentiation and a
      molecular determinant of inhibition.
AB  - The 5-hydroxytryptamine type-3 receptor antagonist tropisetron is in clinical use
      as an anti-emetic drug. This compound also exerts both potentiating and
      inhibitory effects on the glycine receptor chloride channel. The inhibitory
      effects occur at micromolar concentrations, whereas the potentiating effects are
      shown here to occur at femtomolar concentrations at the homomeric alpha1
      receptor. Potentiation occurred only when tropisetron was applied in the presence
      of glycine. We also sought to identify molecular determinants of tropisetron
      inhibition at the alpha1 glycine receptor by serially mutating residues located
      in or near known ligand-binding sites. We discovered that conservative mutations
      to N102 ablated tropisetron inhibition without affecting the magnitude or
      sensitivity of tropisetron potentiation. Several lines of evidence, including a
      structure-activity analysis of tropisetron, atropine and SB203186, suggest that
      N102 may bind to the tropisetron tropane nitrogen via H-bonding. Mutation of the
      N125 residue in the beta subunit, which corresponds to N102 in the alpha1
      subunit, had little effect on tropisetron inhibitory potency. These results show
      that N102 is required for tropisetron inhibition but not potentiation and that
      inhibitory tropisetron binds in different orientations at different subunit
      interfaces. To our knowledge, tropisetron is the most exquisitely sensitive
      modulator yet identified for a cys-loop receptor.

PMID- 17181560
TI  - How to fight antimicrobial resistance.
AB  - Antimicrobial misuse results in the development of resistance and superbugs. Over
      recent decades, resistance has been increasing despite continuing efforts to
      control it, resulting in increased mortality and cost. Many authorities have
      proposed local, regional and national guidelines to fight against this
      phenomenon, and the usefulness of these programmes has been evaluated.
      Multifaceted intervention seems to be the most efficient method to control
      antimicrobial resistance. Monitoring of bacterial resistance and antibiotic use
      is essential, and the methodology has now been homogenized. The implementation of
      guidelines and infection control measures does not control antimicrobial
      resistance and needs to be reinforced by associated measures. Educational
      programmes and rotation policies have not been evaluated sufficiently in the
      literature. Combination antimicrobial therapy is inefficient in controlling
      antimicrobial resistance.

PMID- 17181561
TI  - N-terminal pro-brain natriuretic peptide and coronary artery disease.

PMID- 17181562
TI  - The metabolic syndrome: metabolic changes with vascular consequences.
AB  - Despite criticism regarding its clinical relevance, the concept of the metabolic
      syndrome improves our understanding of both the pathophysiology of insulin
      resistance and its associated metabolic changes and vascular consequences. Free
      fatty acids (FFA) and tumour necrosis factor-alpha (TNF-alpha) play prominent
      roles in the development of insulin resistance by impairing the intracellular
      insulin signalling transduction pathway. Obesity is an independent risk factor
      for cardiovascular disease and strongly related to insulin resistance. In case of
      obesity, FFAs and TNF-alpha are produced in abundance by adipocytes, whereas the
      production of adiponectin, an anti-inflammatory adipokine, is reduced. This
      imbalanced production of pro- and anti-inflammatory adipokines, as observed in
      adipocyte dysfunction, is thought to be the driving force behind insulin
      resistance. The role of several recently discovered adipokines such as resistin,
      visfatin and retinol-binding protein (RBP)-4 in the pathogenesis of insulin
      resistance is increasingly understood. Insulin resistance induces several
      metabolic changes, including hyperglycaemia, dyslipidaemia and hypertension, all
      leading to increased cardiovascular risk. In addition, the dysfunctional
      adipocyte, reflected largely by low adiponectin levels and a high TNF-alpha
      concentration, directly influences the vascular endothelium, causing endothelial
      dysfunction and atherosclerosis. Adipocyte dysfunction could therefore be
      regarded as the common antecedent of both insulin resistance and atherosclerosis
      and functions as the link between obesity and cardiovascular disease. Targeting
      the dysfunctional adipocyte may reduce the risk for both cardiovascular disease
      and the development of type 2 diabetes. Although lifestyle intervention remains
      the cornerstone of therapy in improving insulin sensitivity and its associated
      metabolic changes, medical treatment might prove to be important as well.

PMID- 17181563
TI  - N-terminal pro-brain natriuretic peptide used for the prediction of coronary
      artery stenosis.
AB  - BACKGROUND: The level of the inactive N-terminal fragment of pro-brain (B-type)
      natriuretic peptide (NT-proBNP) is a prognostic marker in patients with acute and
      chronic coronary artery disease (CAD). It might also be valuable for non-invasive
      diagnosis of coronary artery disease. MATERIALS AND METHODS: The NT-proBNP was
      measured in 781 consecutive patients with normal left ventricular function
      referred for coronary angiography owing to symptoms or signs of CAD. The
      diagnostic value of NT-proBNP was assessed for predicting CAD at angiography.
      RESULTS: Elevated NT-proBNP levels were associated with the extent of CAD and
      with the female sex (P < 0.001). The ability of NT-proBNP to predict significant
      coronary disease at angiography was assessed separately for men using a cut-off
      point of 85 pg mL(-1), positive likelihood ratio 2.2 (95% CI, 1.7-3.0), negative
      likelihood ratio 0.53 (95% CI 0.45-0.63) and area under the receiver-operating
      characteristic (ROC) curve 0.72: for women, it was assessed using a cut-off point
      of 165 pg mL(-1), positive likelihood ratio 2.4 (95% CI, 1.7-3.4), negative
      likelihood ratio 0.55 (95% CI, 0.44-0.70) and area under ROC curve 0.71. In
      multiple logistic-regression analysis, NT-proBNP added significant independent
      predictive power to other clinical variables in models predicting CAD (odds ratio
      2.76, 95% CI, 1.76-4.32, P < 0.001). CONCLUSIONS: The NT-proBNP is a marker of
      non-obstructive CAD and of significant coronary stenosis. In conjunction with
      other clinical information, measurement of NT-proBNP with the use of sex-specific
      reference ranges may improve the non-invasive prediction of CAD.

PMID- 17181564
TI  - Effects of cardioversion of atrial fibrillation on endothelial function in
      hypertension or diabetes.
AB  - BACKGROUND: Cardioversion (CV) to sinus rhythm corrects endothelial dysfunction
      secondary to atrial fibrillation (AF). As AF often complicates hypertension and
      diabetes (disorders associated with impaired endothelial function) the study
      probed whether these comorbidities to AF produced an additive effect and to what
      extent CV might be advantageous. MATERIALS AND METHODS: Brachial artery flow
      mediated dilatation (FMD) was evaluated before and after CV in 17 lone AF
      patients (group 1), 16 patients with AF + hypertension (group 2) and 17 patients
      with AF + diabetes type II (group 3), while in supine and head-up tilting (HUT)
      positions, as this is when endothelial vasodilation is emphasized as a
      counterbalance to neurogenic vasoconstriction. RESULTS: After 2 weeks, CV in
      group 1 increased (P < 0.01) supine FMD (from 7.22-->9.50%) and restored its HUT
      potentiation (from 9.31-->17.22%). In group 2, FMD also improved significantly
      with CV (supine from 4.92-->7.11% and HUT from 5.29-->11.83%; P < 0.01). In group
      3, CV did not promote significant FMD changes (supine from 5.12-->4.92% and HUT
      from 4.98-->4.73%). After 3 months, FMD improvement persisted in groups 1 and 2
      with enduring sinus rhythm, but not in those with AF relapse. In group 3, FMD
      remained unchanged regardless of cardiac rhythm. CONCLUSIONS: Cardioversion
      persistently increases supine shear stress endothelial responsiveness and
      restores the orthostatic modulation in AF alone or in association with
      hypertension, but not with diabetes. Differences in background endothelial
      impairment may explain the presence (hypertension) or the absence (diabetes) of
      an additive AF effect in comorbidities, as well as CV results.

PMID- 17181566
TI  - Impaired cardiac autonomic function in women with prior gestational diabetes
      mellitus.
AB  - BACKGROUND: Cardiac autonomic neuropathy is a common dysfunction in manifest
      diabetes mellitus and is associated with duration of diabetes and/or an
      inadequate glycaemic control. Heart rate variability (HRV) reflects autonomic
      heart function. The aim of the present study was to investigate whether in women
      with prior gestational diabetes (GD; pre-type 2 diabetes) alterations of cardiac
      autonomic function can be observed after delivery in relation to insulin
      sensitivity and glycaemic control. MATERIALS AND METHODS: Forty-eight healthy
      women with prior GD were consecutively admitted to the study. HRV was analysed by
      both time, as well as frequency, domain methods using 24-h Holter monitoring. In
      addition, 20 women with normal glucose tolerance during and after pregnancy were
      investigated as control subjects. All women underwent a frequently sampled
      intravenous glucose tolerance test (FSIGT) for measurement of insulin
      sensitivity. RESULTS: Time domain analysis (standard deviation of normal RR
      intervals; SDNN) showed a reduced HRV in 25 out of the 48 (52%) women with prior
      GD. Frequency domain analysis revealed that in these 25 subjects both low and
      high frequency components of power spectral density (reflecting mainly
      sympathetic respectively parasympathetic activity) were reduced, indicating that
      sympathetic as well as parasympathetic functional impairment may be assumed.
      However, a relative predominance of the sympathetic over parasympathetic cardiac
      function was observed. The impairment of cardiac autonomic function (reduced
      SDNN) was correlated with HbA1c values and the 2-h blood glucose concentration
      (oral glucose tolerance test) but not with insulin sensitivity. CONCLUSION: The
      present results demonstrate that in 52% of the women examined who had prior GD,
      an impairment of cardiac sympathetic as well as parasympathetic function was
      present, which related to glycaemic control, but not to insulin sensitivity. This
      infers that functional autonomic changes could be an early prognostic indicator
      in pre-type 2 diabetes.

PMID- 17181565
TI  - Reduced endothelial progenitor cells in European and South Asian men with
      atherosclerosis.
AB  - BACKGROUND: Circulating endothelial progenitor cells (EPCs) play a role in the
      repair and regeneration of the endothelium and may represent a novel
      cardiovascular risk factor. South Asian subjects have an increased risk of
      cardiovascular disease which is not fully explained by known risk factors. This
      study examined associations of EPCs with atherosclerosis and possible ethnic
      differences in EPCs. MATERIALS AND METHODS: A population sample of 58 European
      and South Asian adult men was enriched with the recruitment of an additional 59
      European and South Asian men with known coronary disease. The coronary artery
      calcification score was measured by multi-slice computerized tomography (CT),
      carotid and femoral intima-media thickness (IMT), and femoral plaques were
      measured by ultrasound. The subjects were further subdivided into three
      categories of coronary artery disease on the basis of coronary artery
      calcification score and clinical history. Total EPCs and non-senescent EPCs (ns
      EPCs) were quantified after 5 days cell culture and the number of late outgrowth
      colonies was measured over a 6-week test period. Circulating CD34+ haematopoietic
      precursor cells were measured by flow cytometry. RESULTS: Individuals with
      femoral plaques had reduced total and ns-EPCs. The number of ns-EPCs were reduced
      in individuals with the most coronary atheroma and were inversely related to the
      coronary calcification score and femoral IMT. These relationships persisted after
      multivariate adjustment for other risk factors. The numbers of late outgrowth
      colonies or circulating CD34+ cells were unrelated to the presence of
      atherosclerosis. There were no differences in the number of EPCs between European
      and South Asian subjects. CONCLUSION: The number of EPCs are reduced in subjects
      with atherosclerosis independent of other risk factors. Reduction in EPC numbers
      may be an independent risk factor for atherosclerosis but does not explain ethnic
      differences in cardiovascular risk.

PMID- 17181567
TI  - Serum concentrations of the tissue polypeptide specific antigen in patients
      suffering from non-alcoholic steatohepatitis.
AB  - BACKGROUND: Liver histology is the gold standard for diagnosis of non-alcoholic
      fatty liver disease. Ethical considerations and patient choice often preclude
      performing a liver biopsy, especially considering the rare but potential risk.
      Searching for a good serological marker substitute for the invasive procedure was
      the aim of our study. Keratins, mainly 8 and 18, play not only a mere structural
      role providing mechanical stability to hepatocytes, but also represent a target
      via toxic stress ultimately inducing apoptosis/necrosis. Tissue polypeptide
      specific antigen (TPS), a serological mirror of keratin 18, is widely used as a
      marker for various cancers. This antigen was assessed in three different groups
      who were overweight or obese. MATERIALS AND METHODS: In this cross-sectional case
      control study, 48 cancer-free patients with non-alcoholic steatohepatitis (NASH,
      Group 1), 48 patients with pure fatty liver (FL, Group 2), and 47 volunteers
      (Group 3) were studied. All of them were referred to our metabolic unit for
      routine evaluation. RESULTS: The median (range) TPS levels were 123 (56-286) ng
      mL(-1) in NASH patients. FL patients and volunteers had significantly lower TPS
      levels, 76 (38-98) ng mL(-1) and 64 (28-87) ng mL(-1), respectively (P = 0.0001).
      A value of 88 ng mL(-1) in patients with underlying bright liver was associated
      with a high probability of NASH (sensitivity and specificity = 92% and 96%,
      respectively). One patient (2.1%) with FL had a TPS value > 88 ng mL(-1), but in
      the same group, 29 FL patients (60.4%) had an alanine aminotransferase value > 40
      U L(-1). Based on a recent classification of liver fibrosis, the median (range)
      TPS values were significantly different among the stages: F1 (n = 23) = 100 (76
      264) ng mL(-1); F2 (n = 21) = 134 (56-276) ng mL(-1); and F3 (n = 4) = 199.5 (123
      286) ng mL(-1), respectively (P = 0.014). CONCLUSIONS: Our study shows that TPS
      is a better marker than alanine aminotransferase activity, ultrasonography or the
      combination of both parameters in differentiating NASH from FL.

PMID- 17181568
TI  - Induction of hepatitis C virus (HCV)-specific T cells by needle stick injury in
      the absence of HCV-viraemia.
AB  - BACKGROUND: The risk of hepatitis C virus (HCV) infection after occupational
      exposure is low with seroconversion rates between 0 and 5%. However, factors
      associated with natural resistance against HCV after needle stick injury are
      poorly defined. HCV-specific T-cell responses have been described in cross
      sectional studies of exposed HCV-seronegative individuals. MATERIALS AND METHODS:
      In this study, we prospectively followed 10 healthcare professionals who
      experienced an injury with an HCV-contaminated needle. Blood samples were taken
      on the day or the day after the event and at different time points during follow
      up for up to 32 months. HCV-specific T-cell responses were investigated directly
      ex vivo and in T-cell lines. RESULTS: None of the individuals became positive for
      HCV-RNA in serum tested with the highly sensitive transcription-mediated
      amplification (TMA)-assay or in peripheral blood mononuclear cells (PBMC). All of
      them remained anti-HCV negative throughout follow-up. At the time of injury, HCV
      specific CD4+ T-cell responses were already detectable in two individuals and
      became detectable thereafter in three additional persons. Transient HCV-specific
      CD8+ T-cell responses developed in two HLA-A2 positive patients, which became
      negative until the most recent follow-up after 5 and 17 months, respectively.
      CONCLUSION: We demonstrate the development of HCV-specific T cells in HCV-exposed
      individuals after needle stick injury indicating subinfectious exposure to HCV. T
      cell immunity against HCV may contribute to the low prevalence of HCV in medical
      healthcare professionals in Western countries.

PMID- 17181569
TI  - Relaxation of human placental arteries and veins by ATP-sensitive potassium
      channel openers.
AB  - BACKGROUND: Adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP))
      are important modulators of vascular tone. Preliminary data from our laboratory
      suggests that K(ATP) channels are expressed in the fetoplacental vasculature
      where addition of pinacidil, a specific K(ATP) opener, promotes relaxation. We
      aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental
      vasculature, which are putative K(ATP) channel openers. MATERIALS AND METHODS:
      Functional activity of K(ATP) channels was assessed in chorionic plate arteries
      and veins using wire myography. Cromakalim-, KRN2391- and KRN4884-induced
      relaxations were assessed in the presence and absence of agonist-induced pretone.
      Cromakalim, an established K(ATP) channel opener, acted as control. RESULTS:
      KRN2391 evoked significantly greater relaxation of chorionic plate arteries and
      veins than either KRN4884 or cromakalim. KRN2391-induced relaxation of
      precontracted arteries and veins was reduced in the presence of inhibitors of the
      nitric oxide pathway (L-NNA or LY83583). With KRN4884, there was no contribution
      of nitric oxide to the induced relaxation. CONCLUSIONS: We conclude that K(ATP)
      channels play an important role in controlling placental vascular tone. KRN2391
      induces relaxation of human placental blood vessels by activation of K(ATP)
      channels and via activation of nitric oxide-dependent pathways.

PMID- 17181570
TI  - Expression of the target receptor CD33 in CD34+/CD38-/CD123+ AML stem cells.
AB  - BACKGROUND: CD33 (Siglec-3) is becoming increasingly important as a target of
      antibody-mediated therapy in acute myeloid leukaemia (AML). In normal
      myelopoiesis, expression of CD33 is restricted to advanced stages of
      differentiation, whereas primitive stem cells do not express CD33. In the present
      study, we asked whether leukaemic stem cells in patients with AML express CD33.
      MATERIALS AND METHODS: A multicolour-staining technique was applied in 11
      patients with AML, and leukaemic progenitors defined as CD34(+)/CD38(-)/CD123(+)
      cells. AML stem cells were purified by cell sorting and were examined for
      expression of CD33 mRNA by reverse transcriptase-polymerase chain reaction (RT
      PCR). RESULTS: In all patients in whom the majority of myeloblasts expressed CD33
      (n = 8), AML progenitors reacted with the CD33 antibody P67.6. Repopulation
      experiments utilizing irradiated NOD/SCID mice confirmed that AML stem cells in
      these patients reside within the CD33(+) subpopulation of the leukaemic clone.
      Moreover, highly purified AML stem cells (> 98% purity) from patients with
      CD33(+) AML were found to express CD33 mRNA in RT-PCR analyses. CD33 was neither
      detectable on CD34(+)/CD38(-) cells in normal bone marrow nor on leukaemic stem
      cells in patients with CD33-negative AML. CONCLUSIONS: Leukaemic stem cells in
      patients with CD33(+) AML express CD33. This observation is in favour of novel
      treatment concepts employing CD33-targeting antibodies in AML.

PMID- 17181571
TI  - Use of midregional proadrenomedullin in the detection of myocardial ischaemia.

PMID- 17181573
TI  - Compomers in restorative therapy of children: a literature review.
AB  - OBJECTIVE: The restoration of carious primary teeth plays an underestimated role
      in paediatric dentistry. This is astonishing for many reasons, not least because
      many new materials have been introduced in recent years. New or modified
      techniques and materials, with better aesthetics and flexural properties, allow
      minimally invasive treatment. A transfer of techniques between different
      dentitions, however, may be problematic because of both micromorphological
      differences and compliance. Therefore, this paper deals with options for
      restoring primary teeth and the early stages of the mixed dentition using
      polyacid-modified composites, the so-called compomers. METHODS: Medline and
      Embase were scanned from 1990 through 2006. Furthermore, a hand-search of
      nonlisted but peer-reviewed papers was performed. The search items were
      compomer*, dent*, primary* and deciduous*, which identified 109 relevant
      publications. CONCLUSIONS: Based on high clinical success rates, compomers are
      now an effective alternative to other materials for restorative therapy in the
      anterior and posterior primary teeth. A minimum amount of compliance is still
      mandatory in order to allow for a few minutes of adhesive pretreatment and
      layering without contamination. If this is not the case, compomers make no sense.
      Stainless steel crowns are still the most effective from of restoration for
      severely decayed primary molars.

PMID- 17181574
TI  - Anomalies of tooth formation in hypohidrotic ectodermal dysplasia.
AB  - OBJECTIVE: The X-linked hypohidrotic ectodermal dysplasia (HED) is the most
      common type of ectodermal dysplasia. The clinical identification of possible
      heterozygous females can be difficult because of the varying degrees of clinical
      signs caused by X-chromosome inactivation. This study is the first to elaborate
      on anomalies of tooth formation found in a group of hemizygous males and
      heterozygous females with known ED1 mutations. These tooth anomalies may be used
      as dental biomarkers for heterozygous females, enabling an earlier diagnosis, and
      therefore, better treatment and genetic counselling. METHODS: Anomalies of tooth
      formation were examined using panoramic radiographs, dental casts and oral
      photographs in hemizygous males and heterozygous females who were identified by
      molecular genetic analysis. The results were compared to existing controls and
      normative data. RESULTS: All affected males had multiple missing permanent teeth
      and tooth malformations. The heterozygous females had a significantly higher
      frequency of agenesis of permanent teeth compared to normative data. The
      heterozygous females had an increased prevalence of tooth malformations and
      reduced tooth size, especially in the mesiodistal dimension. CONCLUSIONS: We
      conclude that observed anomalies of tooth formation may be used as dental
      biomarkers in the clinical identification of potentially heterozygous females.

PMID- 17181575
TI  - Children with Down syndrome: oral development and morphology after use of palatal
      plates between 6 and 48 months of age.
AB  - OBJECTIVE: The aim of this study was to describe the number of erupted teeth,
      sucking habits, tongue morphology, facial expression and speech in children with
      Down syndrome (DS) aged 48 +/- 6 months and treated from 6 months of age with
      palatal plates in combination with speech and language therapy. METHODS: The
      research took the form of a multicentre, multidisciplinary, longitudinal study of
      children with DS followed from the age of 6 months. A total of 37 children with
      DS were included. One child could not cooperate at all and was excluded from the
      evaluations. In combination with speech and language intervention provided by
      speech and language therapists, the children used palatal plates provided by
      dentists from 6 months of age. In the evaluation, the children in the sample (n =
      36) were compared with two similarly aged control groups: one group of children
      with DS who never had used palatal plates (n = 31) and one group of children with
      normal development (n = 36). The evaluation of oral parameters was performed by
      dentists after calibration. Registration of facial expression and speech was done
      by a speech and language therapist, and the evaluation was done by two speech and
      language therapists and one phonetician who were calibrated in joint discussions.
      RESULTS: In contrast to the children with DS in the control group, the subjects
      in the study were found to have as many erupted teeth as the children with normal
      development. The prevalence of sucking habits did not differ between the three
      groups. Only children with DS sucked their tongue, a toy or other things in
      addition to a thumb or dummy. The prevalence of tongue diastase in the study
      group with DS was of the same magnitude as in the evaluation at the age of 18 +/-
      3 months. The palatal plates were used by 57-65% of the children without any
      larger problems. In the study sample, the possible beneficial effects of palatal
      plate therapy were a lower prevalence of posterior cross-bite, a higher
      prevalence of frontal cusp-to-cusp relation and a lower prevalence of frontal
      open bite. Evaluation of facial expression and speech showed a higher score for
      facial expression and a better communicative capacity in the children in the
      study group than in the control children with DS. CONCLUSIONS: In children with
      DS, palatal plate therapy between 6 and 48 months of age in connection with
      speech and language intervention had a positive effect on occlusion, oral motor
      function, facial expression and speech. No harmful effects were observed.
      Although this is a valuable method, however, it must be emphasized that palatal
      plate therapy puts additional demands on already burdened children and their
      caretakers.

PMID- 17181576
TI  - The use of theatre time for paediatric dentistry under general anaesthesia.
AB  - OBJECTIVE: The aim of this paper was to determine the use of theatre time for all
      procedures performed under general anaesthetic on a paediatric dental list.
      METHODS: A prospective study of paediatric dental general anaesthetic procedures
      was undertaken at Ninewells Hospital and Medical School, NHS Tayside, Dundee, UK.
      Data were collected prospectively for 71 operating lists over a 3-year period
      from April 2003 to March 2006. Both operator status and the procedure being
      undertaken were recorded. In addition, pre-anaesthetic, anaesthetic, operating
      and disconnection times were recorded. RESULTS: Of the 71 lists examined, 61
      either finished early or on time, with a median unused time of 32.50 min
      (interquartile range = 19.50, 50.00 min), whilst 10 lists finished late with a
      median overrun time of 30.50 min (interquartile range = 9.25, 45.50 min).
      Comparing lists which finished late with those which were completed within time,
      the median pre-anaesthetic time was significantly longer (Mann-Whitney U-test, W
      = 20.05, P = 0.048). Overall, the theatre was in use for 78.22% of time combining
      pre-anaesthetic, anaesthetic, operating and disconnection times; hence, there was
      poor time utilization of theatre for 21.78% of the total theatre time.
      CONCLUSIONS: Overall, 85.9% of theatre sessions for dental procedures under
      general anaesthetic in children finished early or on time. Where lists finished
      late, the duration of the pre-anaesthetic time appeared to be the significant
      factor.

PMID- 17181578
TI  - Social and biological early life influences on the prevalence of open bite in
      Brazilian 6-year-olds.
AB  - OBJECTIVE: Little is known about the effects of social and biological risk
      factors for open bite on the primary dentition. The aim of this study was to
      assess the early-life risk factors affecting anterior open bite. METHODS: A cross
      sectional study using a birth cohort was carried out in Pelotas, Brazil. A sample
      of 400, 6-year-old children was employed. The Foster and Hamilton criteria were
      used to classify open bite. Data concerning social conditions, and perinatal and
      childhood health and behaviour were obtained from birth to 12 months of age and
      during the fifth year of the children's lives. Unconditional bivariate and
      multiple logistic regression analysis were performed. RESULTS: The prevalence of
      anterior open bite was 46.3%. Risk factors included: a maternal age of between 30
      and 39 years, as compared with children whose mothers were younger; breast
      feeding for < 9 months; dental caries experience; pacifier sucking between 12
      months and 5 years, as compared to no sucking or a shorter duration of sucking;
      and the presence of finger-sucking at 6 years of age. CONCLUSION: Open bite in
      the primary dentition was associated with older mothers, early weaning, dental
      caries occurrence, long-term use of a pacifier and finger-sucking at 6 years of
      age. These findings support the common risk approach for intervention to prevent
      open bite in the primary dentition.

PMID- 17181579
TI  - An assessment of rubber dam usage amongst specialists in paediatric dentistry
      practising within the UK.
AB  - OBJECTIVE: Rubber dam is recommended by the British Society of Paediatric
      Dentistry (BSPD) for various restorative and endodontic procedures. To date,
      there has been no report of actual usage of rubber dam within the speciality of
      paediatric dentistry. The aim of this study was to assess the usage of rubber dam
      amongst paediatric dentistry specialists within the UK. METHODS: A postal
      questionnaire was distributed to all practitioners registered on the UK General
      Dental Council's 2004 specialist list in paediatric dentistry. RESULTS: Data were
      available for 162 questionnaires (a 75% response rate), and of these, 85% of
      respondents worked in the National Health Service (NHS), 4% were private
      practitioners and the remainder had a mixed NHS/private practice. Regarding the
      benefits of rubber dam, 65% and 52% of respondents quoted patient safety and
      moisture control, respectively. Perceived difficulties of dam usage were lack of
      patient cooperation and the non-necessity for a particular treatment, as quoted
      in 64% and 36% of the completed questionnaires, respectively. The most common
      modes of isolation for anterior and posterior teeth were Dry Dam(R) (58%), and
      clamp and dam (80%), respectively. CONCLUSION: Current BSPD guidelines recommend
      rubber dam usage for many restorative procedures; however, it would appear that
      there is wide variability in the application, as well as under-use, of rubber
      dam.

PMID- 17181577
TI  - Longitudinal scintigraphic study of parotid and submandibular gland function
      after total body irradiation in children and adolescents.
AB  - OBJECTIVE: Total body irradiation (TBI) and cyclophosphamide (CY) during
      allogeneic stem cell transplantation (ASCT) cause salivary gland dysfunction in
      children. The aim of this investigation was to study the scintigraphic functional
      changes over time of the parotid and submandibular glands in children and young
      adults one year after treatment with CY and TBI at ASCT. METHODS: Salivary gland
      scintigraphy (SGS) was performed before ASCT, and 3-6 months and 12 months after
      ASCT. The three male patients who fulfilled the scintigraphic study had a mean
      age (+/- SD) of 17.3 +/- 9.8 years at ASCT. RESULTS: The parotid secretion
      capacity (SPar) was 83.5 +/- 3.2% before ASCT and 48.5 +/- 25.8% during the next
      3-6 months (P < 0.05). The SPar did not increase (48.1 +/- 12.4%) during the rest
      of the first year after ASCT. The submandibular emptying capacity (SSub) was 91.3
      +/- 12.9% before ASCT and 35.4 +/- 2.3% after 3-6 months (P < 0.05). The SSub was
      87.9 +/- 17.9% one year after ASCT. CONCLUSIONS: The parotid glands were more
      sensitive to irradiation since they did not recover lost capacity to secrete
      saliva, while the submandibular glands recovered the secretion capacity at the
      one-year follow-up.

PMID- 17181580
TI  - Enamel defects and ectopic eruption in a child with Usher syndrome and a cochlear
      implant.
AB  - BACKGROUND: Usher syndrome is a genetic disorder consisting of progressive loss
      of vision and hearing. CASE REPORT: The paper describes an 8-year-old girl with
      Usher syndrome type I who presented with generalized defects of the permanent
      dentition and ectopic eruption of the right maxillary first permanent molar. A
      cochlear implant had been fitted for her hearing loss, and the report reviews the
      implications of this device for dental treatment. The impacted first permanent
      molar was encouraged to erupt into the correct position by shaving the distal
      surface of the second primary molar. CONCLUSION: This is the first report to
      describe in detail an association between Usher syndrome and enamel defects.

PMID- 17181581
TI  - Is amelogenesis imperfecta an indication for renal examination?
AB  - BACKGROUND: The term 'amelogenesis imperfecta' (AI) describes a diverse group of
      hereditary conditions primarily affecting the quality and/or quantity of dental
      enamel. CASE REPORT: This paper describes a case in which hypoplastic AI with
      delayed/failure of eruption of the permanent teeth was shown to be associated
      with renal calcification. CONCLUSION: Given the importance of the renal
      involvement, the authors suggest that paediatric dentists consider referring all
      children with this dental phenotype for renal ultrasound examination.

PMID- 17181582
TI  - Impalement injuries of the oral cavity in children: a case report and survey of
      the literature.
AB  - BACKGROUND: Impalement injuries of the soft palate and oropharynx are common in
      children, especially those of preschool age. These injuries are particularly
      common in toddlers, given their propensity to fall easily while carrying objects
      in their mouths. Although most of these injuries do not have lasting sequelae,
      some can have devastating neurological complications, and consequently, careful
      assessment of the patient during the early stages of trauma is imperative. Close
      follow-up for up to 72 h, and parental counselling and instruction should be
      considered as part of their immediate care. CASE REPORT: A case of toothbrush
      impalement in a 4-year-old child is presented. The foreign body was noted to be
      lodged in the cheek. After careful triaging, history taking and appropriate
      imaging, surgical removal of this brush was carried out uneventfully under
      general anaesthesia. No further complications were noted postoperatively, and
      because of the type of injury, the patient was discharged within 24 h and
      reviewed as an outpatient. CONCLUSION: A survey of the literature confirms that
      most injuries of this kind can be treated conservatively, and in many cases,
      without surgical intervention. However, careful assessment by an experienced
      clinician is necessary to rule out other complications. The present paper
      discusses the prevalence, management and complications associated with impalement
      injuries of the oral cavity in children.

PMID- 17181583
TI  - Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency with inadvertent caries in
      infants.
AB  - BACKGROUND: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a
      rare systemic disease that is associated with early tooth decay. CASE REPORT:
      This report describes the case of a 3-year-old boy suffering from LCHADD. At the
      time of referral, extensive carious lesions of the subject's maxillary dentition
      necessitated the surgical removal of eight teeth. Preventive treatment for LCHADD
      involves a regular oral intake of glucose that is vital for the survival of the
      affected individual. In young infants, the glucose solution needs to be
      administered as often as every 3 h in order to prevent hypoglycaemia, leading to
      a local environment similar to that experienced in nursing bottle syndrome. While
      nursing bottle syndrome can be resolved by eliminating the sugar substrate and
      curtailing the feeding sessions, these alternatives are not available in cases of
      LCHADD. CONCLUSION: This report highlights this rare disease and emphasizes its
      dire consequences for the dentition. Prophylactic recommendations for high-risk
      children are reviewed. Familiarity with LCHADD allows this high-risk group of
      patients to be identified, and thus, ensures diligent prophylactic action.

PMID- 17181584
TI  - Antibodies to a novel antigen in acute hepatitis C virus infections.
AB  - BACKGROUND: Conformational viral proteins potentially play an important role in
      the immunobiology of acute hepatitis C virus (HCV) infection and may enable
      earlier antibody detection. MATERIALS AND METHODS: HCV RNA was detected using
      nucleic acid testing. Early antibody production was evaluated using three enzyme
      immunoassays (EIAs) containing antigenic proteins not present in licensed EIAs.
      Respectively, these contained: (1) multiple-epitope fusion antigen (MEFA) 7.1
      NS3/4a, (2) F and Core, and (3) E1/E2 proteins. NS3/4a is a conformational
      antigen retaining protease and helicase enzymatic activities. MEFA 7.1 contains
      the linear epitopes used in licenced EIAs, including the latest EIA-3.0, in
      combination with genotype 1-3 specific epitopes. Forty-two RNA positive, EIA-3.0
      negative samples, including two persistently serosilent cases, were used to
      evaluate these research EIAs. As controls, 54 EIA-3.0 negative/RNA negative and
      three HCV RNA+/antibody positive specimens were included. RESULTS: Only the MEFA
      7.1-NS3/4a EIA was positive in seven (17%) of the 42 HCV RNA + specimens, in all
      three EIA-3.0 positive controls but in none of 54 EIA-3.0 negative/HCV RNA
      negative controls. Notably, six of the seven (86%) specimens had evidence of
      active hepatitis (ALT > 210 IU/l). The two serosilent cases were research EIA
      negative. CONCLUSION: A novel EIA with conformational and linear epitopes
      detected HCV antibodies in 17% of viraemic specimens missed by the standard
      reference EIA-3.0. Our research EIA appears to detect HCV antibodies closer to
      the initiation of acute hepatitis. Given that the average RNA-positive, antibody
      negative window period is 56.4 days, this 17% yield would translate into a 10-day
      earlier detection of antibodies.

PMID- 17181585
TI  - Analytical and clinical sensitivity of the Procleix Ultrio HIV-1/HCV/HBV assay in
      samples with a low viral load.
AB  - BACKGROUND AND OBJECTIVES: The Procleix Ultrio human immunodeficiency virus type
      1 (HIV-1)/hepatitis C virus (HCV)/hepatitis B virus (HBV) (Ultrio) assay
      simultaneously detects HIV-1 RNA, HCV RNA and HBV DNA in individual blood
      donations. The main objective of the study was to assess the analytical and
      clinical sensitivity of the multiplex and discriminatory probe assays in samples
      with a low viral load. MATERIAL AND METHODS: The VQC HIV RNA genotype B, HCV RNA
      genotype 1 and HBV DNA genotype A standard dilutions were tested in 26 repeats.
      The probability of detection by Ultrio was compared with previously obtained data
      of the Procleix Duplex HIV-1/HCV assay on the same reference panels. A selection
      of 121 anti-HIV-1, 138 anti-HCV and 190 HBsAg positive samples from patients
      receiving antiviral therapy were tested. The majority of patient samples had a
      viral load below the detection limit of the diagnostic nucleic acid test assays,
      which made them suitable to evaluate the performance of the multiplex and
      discriminatory assays on yield cases with a similar low viral load. RESULTS: The
      95% and 50% detection end-points of the Ultrio assay along with the corresponding
      95% confidence intervals are 53.7 (32.9-117.2) and 8.6 (6.2-12.1) geq/ml for HIV
      1 RNA, 30.3 (19.0-62.4) and 5.2 (3.7-7.2) geq/ml for HCV RNA and 393.7 (147.9
      6978) and 54.5 (22.4-143.8) geq/ml for HBV DNA. The analytical sensitivity of
      Ultrio expressed as a potency factor relative to previously obtained Duplex
      results on the same HIV-1 RNA and HCV-RNA standard dilutions was 1.09 (0.20-6.10)
      and 1.11 (0.21-5.89), respectively. The assay detected all 22 HIV-1 infected
      patients with viral load > 50 copies/ml, and 41 of 99 patients (41%) with viral
      load < 50 copies/ml, of which 23 (56%) were detected by the discriminatory assay.
      All 47 patients with HCV RNA load > 521 IU/ml and 10/91 polymerase chain reaction
      negative patients with viral load < 50 IU/ml tested positive in Ultrio assay of
      which five were missed in the discriminatory test. The assay detected 53/55 HBV
      infected patients (96%) with viral load > 250 copies/ml and 108/135 patients
      (80%) with viral load < 250 copies/ml of which 17 (16%) were missed by the
      discriminatory test. CONCLUSIONS: The new Procleix Ultrio assay is as sensitive
      as the Procleix Duplex assay for HIV-1 and HCV detection meeting the requirements
      of universal guidelines. The ability of the assay to detect HBV DNA in low viral
      load samples could be useful for screening blood. Inevitable negative results of
      discriminatory probe assays caused by stochastic sample variation will reduce the
      chance of recognizing low viraemic blood donors detected by individual donation
      nucleic acid test.

PMID- 17181586
TI  - Comparison of three bacterial detection methods under routine conditions.
AB  - BACKGROUND AND OBJECTIVES: Since 2004, bacterial screening of platelets has been
      required in the USA and is also done on a voluntary basis in many European
      countries. The German Red Cross blood donor services conducted a prospective
      multicentre study in order to investigate the prevalence of bacterially
      contaminated pool platelet concentrates and apheresis platelet concentrates. This
      substudy compares three different bacterial detection systems. STUDY DESIGN AND
      METHODS: Platelet concentrates were tested in parallel with BacT/ALERT,
      Scansystem and Pall eBDS (n = 6307) in pool platelets. Apheresis platelets were
      tested in parallel with BacT/ALERT and Pall eBDS (n = 4730). All initially
      positive results were evaluated by a standardized procedure including evaluation
      by a microbiology reference laboratory. RESULTS: One in 6307 pool platelets were
      confirmed positive by BacT/ALERT, whereas Pall eBDS and Scansystem failed to
      detect these samples. Only three samples were initially reactive with Pall eBDS
      without proof of any bacteria strains. The rate of false-positive results was
      substantially higher for BacT/ALERT (0.25%, 28 in 11,037 tested samples) than for
      eBDS (0.03%, 3 in 11 037 tested samples) or Scansystem (0.0%, 0 in 6307 tested
      samples). Three of 4730 apheresis platelets were confirmed positive by
      BacT/ALERT. These were negative with Pall eBDS. CONCLUSION: Sensitivity was best
      for BacT/ALERT, whereas specificity was enhanced for Pall eBDS and Scansystem.
      Scansystem required specially trained staff, whereas BacT/ALERT and Pall eBDS
      were easy, quick, user-friendly and objective methods.

PMID- 17181587
TI  - Extended storage of red blood cells under anaerobic conditions.
AB  - BACKGROUND: Red blood cells (RBC) are subject to oxidative stress by reactive
      oxygen species during refrigerated storage. Near-complete removal of oxygen from
      red cells during storage should eliminate this contributor to the red cell
      'storage lesion'. The in vitro effects of storing red cells under oxygen-depleted
      conditions for extended periods were investigated, and these were correlated with
      the observed recoveries after reinfusion. STUDY DESIGN AND METHODS: Units of red
      cells, obtained after 'soft spin', were placed in a double volume of AS-3
      additive solution and subdivided. Oxygen in the test units was depleted by
      repeated exposure to Ar gas (to O(2) saturation < 4%), and units were stored in
      anaerobic canisters for up to 15 weeks. Samples were taken weekly to monitor
      adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), cell-free
      haemoglobin, and vesicle production. In a parallel experiment, six units of red
      cells was depleted of oxygen in a similar manner, stored for 8, 9 and 10 weeks,
      and reinfused autologously to determine the 24 h post-transfusion recovery via
      (51)Cr/(99m)Tc radiolabelling. A similar study was also carried out using EAS61
      additive solution, which by itself, had shown the ability to support 9-week
      storage, comparing biochemical profiles and in vivo recovery after aerobic vs.
      anaerobic storage. RESULTS: Oxygen-depleted AS-3 units had significantly elevated
      ATP levels compared to controls. They also had significantly lower cell free
      haemoglobin and vesicle production when RBCs were stored for more than 9 weeks.
      An average of over 75% post-transfusion survival was observed after 9 weeks of
      anaerobic storage with less than 0.43% haemolysis. However, no further extension
      of storage was achieved with EAS61 additive. CONCLUSION: Anaerobic conditions
      permit acceptable 9-week storage of RBCs using double-volume AS-3 additive
      solution. It did not synergize with the alkaline, 9-week additive, EAS61, to
      further lengthen the acceptable storage time. These studies indicate that
      anaerobic storage may allow reduction in the effect of the storage lesion, but
      suggest that other factors contribute to limitations of RBC storage as well.

PMID- 17181588
TI  - Sterilization method of platelet storage containers affects in vitro parameters.
AB  - BACKGROUND AND AIM: Four butyryl trihexyl phthalate plasticized polyvinyl
      chloride (BTHC-PVC) containers were compared for storage of leukoreduced platelet
      concentrates (LR-PC): three ethylene oxide (EtO) sterilized (Gambro, Haemonetics,
      Fresenius), and one steam-sterilized (Fresenius). METHODS: LR-PCs were made from
      5 buffy coats and 300 ml Composol additive solution, and leukoreduced by
      filtration. Four LR-PCs were pooled and subsequently divided over the 4 BTHC-PVC
      bags to prevent donor-dependent differences, and sampled for in vitro analysis on
      day 1, 2, 5, 7 and 9. RESULTS: The pH values on day 9 were (mean +/- SD, n = 10):
      7.12 +/- 0.03 (Gambro), 7.12 +/- 0.04 (Haemonetics), and 7.07 +/- 0.09
      (Fresenius, EtO-sterilized) (not significantly different), vs. 6.91 +/- 0.12
      (Fresenius, steam-sterilized; P < 0.001 vs. all EtO-sterilized bags). LR-PCs
      stored in the steam-sterilized bag exhibited significantly higher glucose
      consumption and lactate production (P < 0.001 vs. all EtO-sterilized bags).
      CONCLUSION: All BTHC-PVC containers allow storage of LR-PCs for up to 9 days with
      good in vitro parameters. However, the method of sterilization affects the
      storage conditions of the LR-PCs in these bags.

PMID- 17181589
TI  - Apheresis products of the Amicus and the AS.TEC 204 cell separators are
      comparable with regard to dendritic cells derived from the mononuclear cell
      collection.
AB  - BACKGROUND: In this study, we investigated the quality of autologous mononuclear
      cells (MNC) collected with two different cell separators using standard MNC
      apheresis procedure modalities. MNCs were purified by density gradient
      centrifugation and cultured according to standard protocols to generate dendritic
      cells (DC) and 1 x 10(7)/ml immature DCs were pulsed with tumour lysate for 3
      days and subsequently characterized by fluorescent-activated cell sorter
      analysis. RESULTS: No difference was found in the monocyte content of either
      apheresis product (P = 0.07) and in the overall yield of MNCs (P = 0.7). Mature
      DCs as defined by their phenotype revealed also no significant difference:
      Amicus, 118 x 10(6) cells +/- 91 vs. AS.TEC 204, 128 x 10(6) cells +/- 137 (P =
      0.55), respectively, although the contamination with platelets (threefold) and
      red cells (twofold) was significantly higher in the AS.TEC 204 group (P < 0.05)
      than in the Amicus group. CONCLUSION: The Amicus and the AS.TEC 204 are equally
      capable in providing MNCs for the generation of DCs and the amount of
      concomitantly collected red cells and platelets had no impact on the final DC
      yield.

PMID- 17181590
TI  - A new liquid, intravenous immunoglobulin product (IGIV 10%) highly purified by a
      state-of-the-art process.
AB  - BACKGROUND AND OBJECTIVES: The ultimate goal was to generate an industrial-scale
      process suitable to produce a high-yield, safe and stable immunoglobulin G (IgG)
      preparation for intravenous administration, which is ready to use for customer
      convenience. This new liquid 10% IgG preparation (IGIV 10%) was compared to
      Gammagard SD, a licenced lyophilized immunoglobulin in biochemical and
      preclinical testing. MATERIALS AND METHODS: The new process, which includes three
      dedicated virus clearance steps, is a streamlined combination of the currently
      applied and well-established manufacturing procedures. The biochemical
      characterization is done by standard methods focusing on purity, integrity and
      functionality of the preparation. Efficacy is demonstrated in vivo by mouse
      protection testing and in vitro by opsonization and protein A affinity
      chromatography. Pharmacokinetics in rats is evaluated after a single intravenous
      dose. The anaphylactoid potential is determined in rats and in guinea pigs, while
      thrombogenicity is assessed in a rabbit model. The influence of the products on
      vital functions is tested on dogs, while acute toxicity studies are carried out
      on mice and rats. RESULTS: The biochemical characterization data demonstrate the
      high purity of monomeric IgG in the product. The mouse protection test showed
      that the protective activity against systemic bacterial infections of IGIV 10% is
      at least as good as the reference Gammagard SD. This result is supported by the
      broad spectrum of antibodies in high titres against bacteria and viruses and the
      high functional integrity of the IgG molecule (> or = 90% functionally intact
      IgG) in IGIV 10%. The opsonic activity of all IGIV 10% lots is similar to the one
      of the reference Gammagard SD. In safety and thrombogenicity studies, no adverse
      effects of IGIV 10% were observed. Pharmacokinetic studies showed no
      statistically significant differences between the two products. In the acute
      toxicity animal studies, IGIV 10% compared favourably to the reference Gammagard
      SD. CONCLUSIONS: The new manufacturing process enables the production of a highly
      purified IgG preparation for intravenous administration. The product has an IgG
      subclass distribution similar to plasma and contains a broad spectrum of
      functionally intact antibodies. Preclinical studies demonstrate that the liquid
      IGIV 10% combines excellent qualities of efficacy, safety and tolerability.

PMID- 17181591
TI  - Effect of manufacturing process parameters on virus inactivation by dry heat
      treatment at 80 degrees C in factor VIII.
AB  - BACKGROUND AND OBJECTIVES: Dry heat treatment at 80 degrees C for 72 h is used as
      a virus inactivation step for some coagulation factor concentrates such as Bio
      Products Laboratory's (BPL) factor VIII 8Y. In the current study, the effect of
      this process has been tested on a range of viruses. In addition the effect of
      various manufacturing process parameters on virus inactivation has been
      investigated. MATERIALS AND METHODS: Samples of product intermediate were
      obtained from manufacturing, spiked with virus and subjected to freeze drying and
      dry heat treatment. Virus inactivation was determined by infectivity assay.
      RESULTS: Freeze drying followed by dry heat treatment was effective for
      inactivating a wide range of enveloped and nonenveloped viruses. Sucrose or
      protein concentration had no effect on virus inactivation. Product presentation
      or the interruption of heat treatment also had no effect. The inactivation of
      some of the viruses was greater at higher residual water content but under such
      conditions the stability of the product was reduced. CONCLUSION: This virus
      inactivation step was effective for a wide range of viruses and over the range of
      process conditions encountered in manufacturing. This demonstrates the robustness
      of this process step.

PMID- 17181592
TI  - Portable microscopic cell counter for the determination of residual leucocytes in
      blood components.
AB  - BACKGROUND AND OBJECTIVES: The accurate determination of residual white blood
      cell (WBC) in blood components is of considerable clinical importance, and a
      variety of methods have been devised for the counting of low levels of residual
      WBC. In this study, we evaluated the performance of microscopic cell counter with
      microchannel plastic chip (C-reader) with regard to its ability to quantify WBC
      in WBC-reduced red cell concentrates. MATERIALS AND METHODS: In order to quantify
      residual WBC with the microscopic cell counter, WBC-reduced red cell concentrate
      was stained using propidium iodide. Three studies were performed: linearity,
      precision and correlation compared to those of manual Nageotte chamber counting
      and automatic flow cytometric methods. RESULTS: Dilution experiments, conducted
      over a range of 0.7-712 WBC/microl, showed a linearity of r(2) > 0.999, with
      coefficient of variation values of < or = 15.6% and accuracy of 93.8% over all
      tested ranges. In comparison with the Nageotte chamber counting and flow
      cytometric methods, the correlation coefficients were r(2) > 0.995. The detection
      limit of this method was 0.24 WBC/microl. Total analysis time per sample was
      approximately 5 min. CONCLUSION: The microscopic cell counter for residual WBC
      counting was determined to be efficient at the level of currently defined
      standards, with acceptable precision and accuracy. This method may prove useful
      for the quality assurance and control of WBC-depleted blood products.

PMID- 17181593
TI  - Massive blood transfusion and outcome in 1062 polytrauma patients: a prospective
      study based on the Trauma Registry of the German Trauma Society.
AB  - BACKGROUND AND OBJECTIVES: About 15% of polytrauma patients receive massive blood
      transfusion (MBT) defined as > or = 10 units of packed red blood cells (PRBC). In
      general, the prognosis of trauma patients receiving MBT is considered to be poor.
      The purpose of this study was to investigate the impact of MBT on the outcome of
      polytrauma patients. MATERIALS AND METHODS: Records of 10 997 patients in the
      Trauma Registry of the German Trauma Society were analysed. Transfusion data were
      available from 8182 severe trauma patients with a mean injury severity score of
      24.5 and, of these 8182 patients, 1062 received > or = 10 units of PRBC. First, a
      logistic regression model for the predictors of mortality was performed. Second,
      incidences of organ failure and sepsis as well as survival rates were analysed.
      RESULTS: The highest risk for mortality was age over 55 years (odds ratios [OR]
      4.7; confidence intervals [CI 95%], 3.5-6.5) followed by Glasgow Coma Scale < or
      = 8 (OR 4.6; 3.4-6.1), MBT > or = 20 units of PRBC (OR 3.3; 2.1-5.4),
      thromboplastin time < 50% (OR 3.2; 2.2-4.4) and injury severity score > or = 24
      (OR 2.9; 2.1-4.1). Transfusion of 10-19 PRBC was identified as the variable with
      the lowest risk for mortality (OR 1.5; 1.0-2.3). Risk of organ failure, sepsis
      and death correlated with increasing transfusion amount. For the MBT patients,
      the survival rate was 56.9% (CI 95%, 53.9-59.9%) compared to 85.2% (84.4-86.0%)
      of non-MBT patients (P < 0.001). In the MBT group with > 30 PRBC (mean 40.6 PRBC)
      39.6% survived (31.7-47.5%). CONCLUSION: Massive blood transfusion is one main
      prognostic factor for mortality in trauma. Although MBT is generally considered
      to be critical, every second trauma patient with MBT survived. A cut-off value
      for the number of PRBC could not be determined. Extended transfusion management
      even with high amounts of PRBC seems to be justified.

PMID- 17181594
TI  - Prenatal diagnosis of haemophilia A by chorionic villus sampling and
      cordocentesis: all India Institute of Medical Science experience.
AB  - BACKGROUND AND OBJECTIVE: We looked at the two most commonly used methods for
      prenatal diagnosis, cordocentesis and chorionic villus sampling for prenatal
      diagnosis of haemophilia A in an Indian setting. MATERIAL AND METHODS: The study
      sample included 16 families which reported to us for prenatal diagnosis of
      haemophilia A at All India Institute of Medical Science, New Delhi, India.
      Prenatal tests were done on chorionic villus samples or on cord blood
      (cordocentesis). Molecular work-up included the use of indirect mutation analysis
      in the form of linkage markers like CA-13, CA-22, Xba1 and Bcl1 as well as direct
      mutation analysis in the form of inversion 1 and 22 detection. Non-molecular work
      up included primarily factor VIII assays. RESULT: Chorionic villus sampling was
      performed in eight mothers. Of the other eight mothers, six underwent cord blood
      factor VIII assays because these had absence of family history and were negative
      for linkage and inversion 1 and 22. One patient had a female child and another
      had a fetus that showed congenital abnormalities. CONCLUSION: We found that the
      choice of either technique, chorionic villus or cordocentesis, is not really an
      alternative, but rather dependent on the gestational age of presentation.

PMID- 17181595
TI  - Impact of nonmyeloablative conditioning regimens on the occurrence of pure red
      cell aplasia after ABO-incompatible allogeneic haematopoietic stem cell
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: In the setting of major ABO-incompatible allogeneic
      haematopoietic stem cell transplantation (HSCT), pure red cell aplasia (PRCA) is
      linked to the persistence of host residual plasma cells secreting antidonor
      isohaemagglutinins (HA) after transplantation. There are conflicting results
      regarding the impact of the intensity of conditioning regimen on the occurrence
      of PRCA after major ABO-mismatched HSCT. MATERIAL AND METHODS: To address this
      question, we compared two cases occurring after nonmyeloablative (NMA) and
      myeloablative (MA) HSCT and reviewed previous cases reported in the NMA setting.
      RESULTS AND CONCLUSIONS: We observed a delayed disappearance of antidonor HAs in
      the NMA setting, associated to a more prolonged period of red blood cells
      transfusion dependence than in the MA setting. In our case as in several others,
      the disappearance of antidonor HAs and resolution of PRCA were observed after
      reinforcement of the graft-versus-host effect (i.e. immunosuppression removal or
      donor leukocytes infusion).

PMID- 17181596
TI  - International forum on 'Perioperative blood salvage': a Spanish contribution.

PMID- 17181598
TI  - Melatonin and sleep disorders associated with intellectual disability: a clinical
      review.
AB  - BACKGROUND: Melatonin is used to treat sleep disorders in both children and
      adults with intellectual disability (ID), although it has no product license for
      such use. The evidence for its efficacy, potential adverse effects and drug
      interactions are reviewed in the context of prescribing to people with ID.
      METHODS: A literature search was performed using multiple electronic databases.
      More literature was obtained from the reference lists of papers gathered through
      the searches. RESULTS: Most of the studies were uncontrolled and the few
      controlled trials available were of small size. Melatonin appears effective in
      reducing sleep onset latency and is probably effective in improving total sleep
      time in children and adolescents with ID. It appears to be ineffective in
      improving night-time awakenings. Melatonin is relatively safe for short-term use.
      Its safety for long-term use is not established. Potential drug interactions,
      possible effects on puberty and concerns regarding the use of melatonin in
      epilepsy, asthma and depressive disorders are discussed. CONCLUSIONS: Melatonin
      appears to be an effective sleep-initiator for children and adolescents with ID
      and probably has a similar effect for adults. There may be heterogeneity of
      response depending on the nature of the sleep problem and cause of the ID or
      associated disabilities. Further studies are necessary before firm conclusions
      can be drawn and guidelines for the use of melatonin for people with ID
      formulated.

PMID- 17181599
TI  - An evaluation of Beck's cognitive theory of depression in adults with
      intellectual disability.
AB  - BACKGROUND: The theories supporting cognitive treatment for depression among
      individuals with intellectual disability (ID) have not been formally tested with
      this population. The current study evaluated Beck's cognitive theory of
      depression to determine its appropriateness for adults with ID. METHODS: Forty
      eight adults with primarily mild or moderate ID participated in semi-structured
      interviews, twice approximately 16 weeks apart, as did an additional 12 adults
      diagnosed with depression. Participants reported on depressed mood, the cognitive
      triad, as measured by views of the self, the world and the future, hopelessness
      and self-esteem. RESULTS: The Cognitive Triad Inventory for Children (CTI-C)
      displayed adequate psychometric properties in this sample. In addition, it was
      correlated with depressed mood, and individuals diagnosed with depression had
      significantly higher scores on the CTI-C than those with no psychiatric
      diagnoses. Contrary to hypotheses, a negative cognitive triad did not predict
      depressed mood 4 months later, but the inverse relationship where depressed mood
      predicted a later negative cognitive triad approached statistical significance.
      CONCLUSIONS: The findings indicate that the cognitive triad can be measured among
      individuals with mild or moderate ID and is related to depression and depressed
      mood. However, the role of the cognitive triad in the development of depression
      is still unknown. The findings provide some support for Beck's cognitive theory
      of depression among individuals with ID and provide suggestions for further
      testing the theory. Implications for the treatment of depression among
      individuals with ID are discussed.

PMID- 17181600
TI  - What symptoms predict the diagnosis of mania in persons with severe/profound
      intellectual disability in clinical practice?
AB  - BACKGROUND: While researchers have attempted to address the difficulties of
      diagnosing affective disorders in the intellectually disabled population,
      diagnosing bipolar disorder in an individual with severe intellectual disability
      (ID) remains a challenge. The aim of this study was to identify what symptoms can
      predict a diagnosis of mania in the intellectually disabled population. METHODS:
      Three groups of persons with ID participated in this study: (1) individuals with
      a bipolar diagnosis who were currently manic; (2) individuals with an Axis I
      diagnosis other than bipolar disorder; and (3) individuals without an Axis I
      diagnosis. Two recognized measures of mania (i.e. Diagnostic Assessment for the
      Severely Handicapped-Revised and Parent Version of Young Mania Rating Scale) were
      used to evaluate symptoms of mania. A logistical regression procedure was
      conducted on mania items to identify which items correctly identify persons with
      ID who were currently manic. RESULTS: Psychomotor agitation, decreased sleep,
      changes in mood and aggression were significantly related to the diagnosis of
      mania. Further, psychomotor agitation and disturbed sleep were significant
      predictors of a diagnosis of mania. CONCLUSIONS: Problems of sleep and
      psychomotor agitation should alert clinicians that further assessment of bipolar
      symptomatology is warranted. Focusing on observable behaviours based on
      Diagnostic and Statistical Manual of Mental Disorder-IV criteria can be useful in
      formulating a diagnosis of bipolar disorder in persons with ID.

PMID- 17181602
TI  - Risk factors for psychiatric disturbance in children with intellectual
      disability.
AB  - BACKGROUND: Children with intellectual disability (ID) have a higher risk for
      psychiatric disturbance than their peers with normal intelligence, but research
      data on risk factors are insufficient and partially conflicting. METHOD: The
      subjects comprised 75 children with ID aged 6-13 years. Data were obtained from
      case files and the following four questionnaires completed by their parents or
      other carers: Developmental Behaviour Checklist, American Association of Mental
      Deficiency (AAMD) Adaptive Behavior Scale, a questionnaire on additional
      disabilities, and a questionnaire on family characteristics and child
      development. RESULTS: The risk of psychopathology was most significantly
      increased by moderate ID, limitations in adaptive behaviour, impaired language
      development, poor socialization, living with one biological parent, and low socio
      economic status of the family. CONCLUSIONS: The risk of psychopathology in
      children with ID is increased by factors related to family characteristics and
      child development. Identifying these factors will help diagnose and possibly
      prevent psychiatric disorders in these children.

PMID- 17181601
TI  - The course and outcome of psychiatric illness in people with Prader-Willi
      syndrome: implications for management and treatment.
AB  - BACKGROUND: This study is part of a larger UK-wide study investigating
      psychiatric illness in people with Prader-Willi syndrome (PWS), and describes the
      longitudinal aspect of psychiatric illness, in particular psychotic illness, and
      examines the use and role of psychotropic medication. METHOD: A total of 119
      individuals with genetically confirmed PWS were included in the study. An
      informant-based questionnaire was administered for each participant to screen for
      a history of psychopathology. Those who screened positive were visited at their
      homes to obtain further information. This assessment included a full psychiatric
      history and mental state examination using the Psychiatric Assessment Schedule
      for Adults with Developmental Disability and the Operational Criteria Checklist
      for psychotic and affective illness to collect information regarding
      phenomenology and course of illness, and a modified life events questionnaire. At
      the end of the study period, informant-based telephone interviews were again
      carried out, up to 2.5 years after the initial screening. Information regarding
      medication usage was collected. RESULTS: The results confirm previous findings
      that psychiatric illness in people with PWS resembles an affective disorder.
      Individuals with the maternal uniparental disomy genetic subtype had a more
      severe course of illness than those with the deletion genetic subtype in terms of
      a greater risk of recurrence, more episodes, higher incidence and a possibly
      poorer response to medication with more side-effects. Individuals with a
      recurrent episode during the follow-up period had a poorer course of illness.
      Selective serotonin reuptake inhibitor medication is frequently used, and
      beneficial effects may reflect fundamental pathological processes in PWS. Mood
      stabilizing medication was found to be of little benefit and reasons for this are
      examined. CONCLUSION: The longitudinal course of psychiatric illness and response
      to medication in people with PWS is fully described. Further research is needed
      regarding the effect of psychotropic medications, particularly mood-stabilizing
      medication. These data will enable informed decisions to be made regarding
      management options and provide information on the possible long-term outcome of
      illness.

PMID- 17181603
TI  - Behavioural equivalents of anxiety in children with fragile X syndrome: parent
      and teacher report.
AB  - BACKGROUND: Identifying many of the diagnostic criteria for anxiety and
      depression in individuals with intellectual disability (ID) can be challenging
      because they may be unable to recognize and communicate their emotional
      experiences accurately. The purpose of this study is to identify behavioural
      equivalents of anxiety in children with fragile X syndrome (FXS), the leading
      inherited cause of ID. METHODS: Parents and teachers of 43 children (aged 6-14
      years) with full mutation FXS completed two standardized questionnaires on
      children's problem behaviour and psychiatric symptoms. Items from the
      questionnaires thought to be possible behavioural equivalents of anxiety were
      identified and grouped into four domains: Avoidance Behaviours - Confrontational;
      Avoidance Behaviours - Non-confrontational; Anxiety Continuum Behaviours; and
      Behavioural Dysregulation. The mean rating for the four groups of items was used
      to predict the children's status for exhibiting significant problems with anxiety
      as defined by the Diagnostic and Statistical Manual of Mental Disorders-oriented
      Anxiety Subscale from the problem behaviour scale. RESULTS: The predictor
      variables classified 81% (parent rating) and 86% (teacher rating) of the children
      correctly. Avoidance Behaviours - Confrontational and Avoidance Behaviours - Non
      confrontational (teacher rating) and Anxiety Continuum Behaviours (parent and
      teacher rating) made unique contributions to the models. CONCLUSIONS: Children
      who are unable to identify and communicate that they worry about general day-to
      day events may exhibit more observable behaviours resembling active and passive
      avoidance (e.g. arguing, avoiding difficult tasks, staring off) or have specific
      phobias and compulsions. These findings suggest that there are behavioural
      equivalents for anxiety disorder in children with FXS and, more generally,
      support the notion of behavioural equivalents in ID.

PMID- 17181605
TI  - Queensland psychiatrists' attitudes and perceptions of adults with intellectual
      disability.
AB  - BACKGROUND: Quality mental health care for adults with an intellectual disability
      (ID) depends upon the availability of appropriately trained and experienced
      psychiatrists. There have been few surveys of psychiatrists working with this
      population. METHOD: This Australian study obtained psychiatrists' attitudes to
      and perceptions of the mental health needs of adults with an ID. Training needs
      were also sought. The survey instrument used was a purposely designed, 28-item
      self-administered questionnaire featuring multiple-choice and open-ended
      questions. RESULTS: The majority of psychiatrists expressed concerns about
      treatment of this group, describing unmet needs. A total of 75% considered that
      antipsychotics were overused to control aggression, and 34% of psychiatrists were
      reluctant to treat adults with an ID. In total, 85% agreed that mental health in
      ID should be offered as a training option for psychiatric registrars, and that
      specialized mental health services would provide a high standard of care for this
      population. CONCLUSION: Broad concerns are raised regarding pathways to mental
      health care for adults with an ID in Australia. An Australia-wide training
      strategy needs to be developed. Partnerships between mental health, disability
      and community services that serve the mental health needs of this population,
      should actively seek to engage psychiatrists.

PMID- 17181606
TI  - Prevention of clozapine-induced granulocytopenia/agranulocytosis with granulocyte
      colony stimulating factor (G-CSF) in an intellectually disabled patient with
      schizophrenia.
AB  - BACKGROUND: While clozapine is an effective treatment for refractory
      schizophrenia, its use is limited by haematological side effects. Treatment
      options that allow continued prescription of clozapine by tackling these side
      effects will greatly aid patients for whom this medication is all too often their
      only hope of recovery. METHOD: In this case report, we describe what we believe
      are two 'firsts' in the clozapine literature: the use of granulocyte-colony
      stimulating factor on a prophylactic basis in an intellectually disabled patient
      receiving clozapine for refractory schizophrenia. RESULT: Treatment with
      granulocyte-colony stimulating factor prevented discontinuation of clozapine,
      enabling our intellectually disabled patient's recovery from a schizophrenic
      illness.

PMID- 17181604
TI  - Integrative treatment in persons with intellectual disability and mental health
      problems.
AB  - BACKGROUND: Clinical experience has proven thus far that a monodisciplinary
      treatment approach to behavioural and psychiatric problems in persons with
      intellectual disability (ID), such as psychotropic medication or behaviour
      modification programmes, has yielded limited success. It is clear that the
      complexity of behavioural and psychiatric problems in this population calls for a
      treatment approach from different perspectives. METHODS: A multidimensional
      treatment approach to the persons with ID who suffer from behaviour problems and
      psychiatric disorders is described. RESULTS: Four dimensions - biological,
      psychological, social and developmental - are represented as well in an
      integrative diagnosis as in an integrative treatment, embodied by cooperation of
      different professionals, such as a psychiatrist, psychologist, pedagogues, social
      worker, nurse and, where possible, the person's caretakers. The developmental
      dimension receives a salient attention of assessors. By introducing the
      developmental dimension in diagnostics and treatment, the bio-psycho-social
      dimensions are set in a new context, more appropriate for persons with ID.
      CONCLUSION: The integrative treatment should not be primarily directed towards
      the symptoms of the disorder but towards restoring a person's mental well-being.
      The disorder is combated through treatment of the underlying processes that have
      led to its onset. Different treatment methods from different perspectives may be
      applied. Strategy and methodological procedures of an integrative treatment are
      discussed by way of case presentations.

PMID- 17181609
TI  - Is the use of 'race' in epidemiological studies useful?

PMID- 17181611
TI  - Gillies Lecture: ocular motility in a time of paradigm shift.
AB  - Abstract Recent progress in understanding of the structure and function of
      extraocular muscles, and our ability to image them clinically, allows prediction
      of revolutionary progress in diagnosis and treatment of strabismus in the coming
      decades. This perspective memorializes a lecture given in honour of Dr William
      Gillies, who has for decades been the paternal leader of strabismology in
      southern Australia.

PMID- 17181613
TI  - Dynamic contour tonometry: principle and use.
AB  - Interindividual variability of central corneal thickness has been found to be a
      source of error for conventional Goldmann applanation tonometry. The dynamic
      contour tonometer represents a potentially new technology for non-invasive and
      direct intraocular pressure (IOP) measurement, and has been proposed to
      accurately measure the true IOP irrespective of the corneal thickness. It is
      based on the principle that when the tip of the device exactly matches the
      contour of the cornea, the pressure measured by a transducer placed on its tip is
      an accurate indicator of the true IOP. This device is also capable of measuring
      the ocular pulse amplitude, a variable that has controversial significance in the
      diagnosis and management of glaucoma. Even though this technique seems to be very
      promising, further studies are required to conclusively determine the
      effectiveness of the dynamic contour tonometer in patients having an abnormal or
      irregular corneal contour.

PMID- 17181612
TI  - Failure of medical therapy despite normal intraocular pressure.
AB  - The disease glaucoma is now defined by characteristic optic disc and visual field
      change, without specific reference to the intraocular pressure (IOP). Success of
      treatment is no longer judged by the mere attainment of IOP less than 21 mmHg.
      Controversy remains, however, in deciding appropriate management where optic disc
      and/or visual field damage continues to progress despite a 'normal' IOP having
      been achieved with medical treatment. A panel of international glaucoma experts
      has provided management recommendations in four clinical scenarios--open-angle
      glaucoma, open-angle glaucoma in a myopic contact lens wearer, uveitic glaucoma
      and open-angle glaucoma in combination with visually significant cataract--where
      optic nerve and visual field progression has continued despite an IOP less than
      21 mmHg on full medical treatment. Surgical intervention with mitomycin
      trabeculectomy is the most favoured further therapy.

PMID- 17181614
TI  - A surgical technique with connective tissue repair for the management of
      subconjunctival orbital fat prolapse.
AB  - Abstract Subconjunctival orbital fat prolapse is an uncommon benign entity. In
      addition to insufficient information concerning the mechanisms of the prolapse,
      detailed surgical methods that can be followed are uncommon in the literature. We
      prospectively studied six consecutive eyes in four males who were to undergo our
      novel surgical sequence, attempting to avoid postoperative complications by
      reconstructing intermuscular septa on the basis of the assumption that the
      spontaneous prolapsed fat at the superior temporal quadrant stemmed from
      intraconal fat. Intraoperative findings were in agreement with our hypothesis
      that the anterior part of the herniated fat is covered by both the intermuscular
      septum and Tenon's capsule. All the surgeries were uneventful and cosmetic
      improvement without postoperative complications was obtained. Our early results
      indicated the safety and efficacy of this newly developed technique for
      spontaneous orbital fat prolapse.

PMID- 17181615
TI  - Combined positron emission tomography/computed tomography for evaluation of
      presumed choroidal metastases.
AB  - BACKGROUND: Choroidal metastases are the most common intraocular malignancy and
      are the first sign of systemic malignancy in approximately one-third of patients.
      Of patients with no previous diagnosis of cancer, oncological evaluation fails to
      find the primary lesion in approximately 50% of cases. Newer imaging modalities
      such as combined positron emission tomography/computed tomography (PET/CT) may
      improve the yield of the systemic work-up. METHODS: Consecutive patients
      presenting with presumed choroidal metastases were evaluated with whole body
      combined PET/CT scanning. RESULTS: Four patients presenting to a tertiary
      referral hospital with choroidal metastases as the first sign of systemic
      malignancy were evaluated. In all four cases, PET/CT demonstrated the ocular
      lesion, and the primary malignancy which was confirmed by tissue biopsy. False
      negative results were seen in two cases of cerebral metastases. PET/CT
      demonstrated lesions not visible on CT or magnetic resonance imaging in two
      cases. CONCLUSIONS: Combined PET/CT is a useful addition to the work-up of
      patients with choroidal metastases. It provides the opportunity to detect lesions
      not visible with other imaging modalities and the ability to image patients with
      contraindications to magnetic resonance imaging. It is essential to correlate PET
      images with clinical information and the results of other imaging modalities and
      tissue biopsy remains the gold standard in the diagnosis of malignancy. False
      positives and negatives can occur with PET/CT, and further research is needed
      before this promising technology becomes a routine part of the evaluation of
      patients with choroidal metastases.

PMID- 17181616
TI  - Optic nerve head parameters of an indigenous population living within Central
      Australia.
AB  - PURPOSE: Clinical examination of the optic disc is an essential element in the
      assessment of its health. Previous work has described normal optic disc
      appearance among different races. No such description of optic discs exists for
      indigenous Australians, who are at low risk of developing glaucoma. This study
      was designed to evaluate optic disc parameters of indigenous Australians.
      METHODS: A sample of 208 indigenous Australians were recruited as they presented
      to remote clinics in Central Australia. Each subject underwent optic disc
      photography using a Topcon TRC-NW100 digital fundus camera. Optic discs were
      measured and analysed with Topcon ImageNet 2000 software. RESULTS: Among other
      parameters, mean vertical disc diameter and disc area were 2.13 +/- 0.21 mm (mean
      +/- SD) and 3.13 +/- 0.57 mm2, respectively, for right eyes and 2.14 +/- 0.21 mm
      and 3.16 +/- 0.58 mm2 for left eyes. When compared with published studies, these
      parameters were significantly larger than Caucasians, but similar to African
      individuals. CONCLUSION: Our results suggest that indigenous Australians have
      optic discs that are larger than those of Caucasians, but similar to those of
      Africans who are considered to at a greater risk of glaucoma. Factors other than
      optic disc area are likely to underlie the higher prevalence of primary open
      angle glaucoma among African individuals.

PMID- 17181618
TI  - Clinical evaluation using Custom Control Software technology in coaxial
      phacoemulsification.
AB  - PURPOSE: The aim of this study was to evaluate the clinical outcomes of the
      Custom Control Software technology in coaxial phacoemulsification. METHODS: This
      prospective, randomized, double-masked clinical trial was conducted at the Eye
      Center, Affiliated Second Hospital, College of Medicine, Zhejiang University. The
      patients were grouped according to nuclear sclerosis and randomly assigned to
      undergo conventional phacoemulsification or phacoemulsification using Millennium
      Custom Control Software (CCS). All surgeries were performed by a single surgeon.
      The phaco time and average power of phacoemulsification were recorded and then
      calculated as absolute phaco time (APT). Visual acuity, pachymetry, endothelial
      cell density and anterior chamber flare count of both groups were noted at
      preoperatively day 1 and 3 months after surgery. RESULTS: The APT of the CCS
      group was statistically lower than Conventional group in grades II, III and IV (P
      < 0.05) nuclear sclerosis, but the two groups had no statistically significant
      differences in the grade I group. At day 1 post surgery, there were significant
      differences in the thickened pachymetry (P = 0.047) and anterior chamber flare
      counts (P = 0.008) between two groups. At 3 months post surgery, the endothelial
      cell loss ratio showed statistical difference (P = 0.032) between two groups.
      CONCLUSIONS: Using CCS technology in coaxial phacoemulsification can provide
      lower APT and better power efficiency. This new power modulation may make the
      surgery safer and more effective than Conventional phacoemulsification.

PMID- 17181617
TI  - Outcomes of autoconjunctival grafting for primary pterygia when performed by
      consultant compared with trainee ophthalmologists.
AB  - PURPOSE: To define rates of recurrence and surgical complications of primary
      pterygia excision with autoconjunctival grafting when the surgery is performed by
      consultant ophthalmologists compared with trainee ophthalmologists. METHODS: A
      total of 174 patients with primary pterygia treated by excision and
      autoconjunctival grafting were included for analysis. Patients were divided into
      two groups according to whether their surgery was performed by a consultant
      ophthalmologist (group A) or a trainee ophthalmologist (group B). Data were
      collected with respect to demographics, surgical complications and recurrence.
      Recurrence rates were analysed utilizing Fisher's exact test. Additionally,
      Kaplan-Meier survival curves for interval censored data were constructed.
      Surgical complications were analysed utilizing Fisher's exact test. RESULTS: The
      recurrence rate in group A was 6.8% and in group B was 19.4%. This difference was
      statistically significant (P = 0.05). The rate of surgical complication occurring
      in group A was 6.6% and in group B was 23.3% and this was also statistically
      significant (P = 0.005). No relationship was found between either patient age or
      the size of pterygium and recurrence or complications in either group A or group
      B. CONCLUSION: Autoconjunctival grafting is regarded as the gold standard for
      preventing pterygium recurrence following excision. This study suggests that the
      experience of the surgeon can influence success rates and complications. There is
      a significant learning curve indicating the need to supervise trainee surgeons.

PMID- 17181619
TI  - Outcome of posterior capsulotomy in late capsular block syndrome with posterior
      capsular opacification.
AB  - BACKGROUND: To examine the results of neodymium:yttrium-aluminium-garnet (Nd:YAG)
      laser posterior capsulotomy in eyes with late or previously unrecognized capsular
      block syndrome (CBS) presenting with deterioration of vision owing to posterior
      capsular opacification (PCO). METHODS: Patients, who underwent uneventful
      phacoemulsification with intraocular implantation and were referred for Nd:YAG
      laser capsulotomy owing to PCO, were prospectively examined for the presence of
      CBS. When indicated, Nd:YAG laser posterior capsulotomy was carried out.
      Prospective follow-up examinations were performed for the next 6 months. The
      outcome measures were post-laser change in best corrected visual acuity,
      refraction, change in intraocular pressure, inflammation and complication rate.
      RESULTS: Of 655 patients referred for capsulotomy, eight had an associated CBS in
      that eye. These eight eyes comprised the study cases. The presence of CBS had not
      been recognized before the development of PCO. Best corrected visual acuity
      improved in all cases. In seven out of eight (87.5%) eyes refraction was
      unchanged throughout the follow up. Ocular hypertension, inflammation or other
      complications did not develop. CONCLUSION: Nd:YAG laser capsulotomy in eyes with
      PCO and late or previously unrecognized CBS is a safe procedure, resulting in
      improved visual acuity without refractive change.

PMID- 17181620
TI  - Cataract and its surgery in Timor-Leste.
AB  - PURPOSE: To determine the prevalence of visually significant and unoperated
      blinding cataract, and the coverage, characteristics and outcome of cataract
      surgery in Timor-Leste. METHODS: Based on the World Health Organization Rapid
      Assessment of Cataract Surgical Services protocol, a population-based cross
      sectional survey was conducted in 2005. By two-stage cluster random sampling, 50
      clusters of 30 people aged 40 years and older were selected. Each eye with a
      presenting visual acuity worse than 6/18 and/or a history of cataract surgery was
      examined. RESULTS: Of the 1470 people enumerated, 96.2% were examined. Of the
      eyes examined, 11.5% were blind (presenting vision less than 6/60). Cataract
      caused 66.3% of this, and 40.2% of vision impairment (presenting vision less than
      6/18). For those people who were blind (7.7%; presenting vision less than 6/60 in
      the better eye), cataract was the most frequent cause (76.1%). Cataract surgery
      had occurred in 2% of participants. Gender and domicile were not associated with
      cataract blindness or surgery. Cataract Surgical Coverage (6/60) was 16.3% for
      Eyes and 20.2% for Persons. Surgical outcomes were poor, falling well short of
      World Health Organization guidelines. Astigmatism and posterior capsule opacity
      were important contributors to this. CONCLUSIONS: Until census data are
      available, age-gender-domicile correction of sample findings cannot be
      calculated. In the meantime, it is estimated there are 11 500 cataract blind in
      Timor-Leste. Long-term, indigenous cataract surgical services need to be capable
      of significantly increased output. Better surgical outcomes are required to
      ensure scarce resources are well used. Laser capsulotomy needs to be planned for
      as surgical numbers increase.

PMID- 17181621
TI  - Cataract and its surgery in Papua New Guinea.
AB  - PURPOSE: To determine the prevalence of visually significant cataract, unoperated
      blinding cataract, and cataract surgery for those aged 50 years and over in Papua
      New Guinea. Also, to determine the characteristics, rate, coverage and outcome of
      cataract surgery, and barriers to its uptake. METHODS: Using the World Health
      Organization Rapid Assessment of Cataract Surgical Services protocol, a
      population-based cross-sectional survey was conducted in 2005. By two-stage
      cluster random sampling, 39 clusters of 30 people were selected. Each eye with a
      presenting visual acuity worse than 6/18 and/or a history of cataract surgery was
      examined. RESULTS: Of the 1191 people enumerated, 98.6% were examined. The 50
      years and older age-gender-adjusted prevalence of cataract-induced vision
      impairment (presenting acuity less than 6/18 in the better eye) was 7.4% (95%
      confidence interval [CI]: 6.4, 10.2, design effect [deff] = 1.3). That for
      cataract-caused functional blindness (presenting acuity less than 6/60 in the
      better eye) was 6.4% (95% CI: 5.1, 7.3, deff = 1.1). The latter was not
      associated with gender (P = 0.6). For the sample, Cataract Surgical Coverage at
      6/60 was 34.5% for Eyes and 45.3% for Persons. The Cataract Surgical Rate for
      Papua New Guinea was less than 500 per million population per year. The age
      gender-adjusted prevalence of those having had cataract surgery was 8.3% (95% CI:
      6.6, 9.8, deff = 1.3). Vision outcomes of surgery did not meet World Health
      Organization guidelines. Lack of awareness was the most common reason for not
      seeking and undergoing surgery. CONCLUSION: Increasing the quantity and quality
      of cataract surgery need to be priorities for Papua New Guinea eye care services.

PMID- 17181622
TI  - Giant cell angiofibroma of the orbit with periosteal adherence.
AB  - We report a case of orbital giant cell angiofibroma, an unusual, recently
      reported benign spindle cell neoplasm. Preoperative clinical assessment and
      radiology suggested a benign mass and early operative findings were in
      concordance with this. Surgical excision was however, hampered by periosteal
      adhesion and lack of distinct encapsulation in the posterior part of the lesion.
      The histology of giant cell angiofibroma and its principle pathological
      differential diagnoses is discussed. As with some lymphangiomas, this is another
      benign orbital tumour which may present difficulties in complete surgical
      excision that are not anticipated based on the preoperative findings.

PMID- 17181623
TI  - Pseudoepitheliomatous hyperplasia mimicking ocular surface squamous neoplasia
      following cultivated limbal epithelium transplantation.
AB  - A 12-year-old girl with total limbal stem cell deficiency in the right eye
      following chemical burns underwent autologous cultivated limbal epithelium
      transplantation from the healthy left eye. Postoperatively at 6 weeks a mass at
      the limbus was noted, which increased in size and involved infero-nasal limbus
      extending over 5 mm on bulbar conjunctiva. It was a gelatinous, placoid freely
      movable mass with irregular surface, multiple intralesional cysts without feeder
      vessels or intrinsic vascularization and stained brilliantly with rose bengal.
      Histopathology following excision biopsy showed hyperplastic epithelium with
      stratified columnar cells and goblet cells. At the last follow-up, 6 months
      following cultivated limbal epithelium transplantation the ocular surface was
      stable without any recurrence of the lesion. We herein report a rare complication
      of epithelial hyperplasia presenting as leukoplakia following cultivated limbal
      epithelium transplantation mimicking ocular surface squamous neoplasia.

PMID- 17181625
TI  - Bilateral macular cyst after lightning visualized with optical coherence
      tomography.
AB  - The authors report a 14-year-old girl who was struck by lightning with bilateral
      macular cyst that was diagnosed with optical coherence tomography (OCT). Her
      fundus examination revealed bilateral macular lesions that simulated macular
      holes. The Watzke-Allen sign was negative in the right eye and positive in the
      left eye. Fluorescein angiography showed a foveal window defect in both eyes. OCT
      demonstrated a small foveal cyst evident as a hyporeflective lucency, visible
      just anterior to the retinal pigment epithelium/choriocapillaris complex in both
      eyes. OCT seems to be useful in the evaluation of lighting maculopathy to rule
      out full-thickness macular hole in these cases, and avoid unnecessary surgery.

PMID- 17181626
TI  - Corneal injury by wild taro.
AB  - We report a case of crystalline keratopathy caused by Alocasia macrorrhiza. The
      diagnosis was made based on the observation of needle-like crystals in the
      corneal stroma following injury to that eye. The condition resolved in 3 months
      with the disappearance of the crystals confirmed by follow-up confocal
      microscopy.

PMID- 17181627
TI  - Spontaneous resolution of corneal oedema after inadvertent 'descemetorhexis'
      during cataract surgery.
AB  - A 96-year-old lady underwent cataract surgery complicated by the loss of a 5.5 mm
      diameter area of Descemet's membrane (DM) centrally. Postoperatively, severe
      corneal oedema with folds in the remaining annular ring of DM were observed. The
      patient was managed conservatively and the corneal oedema gradually resolved over
      5 months. Loss of DM can be managed conservatively with good visual outcome
      without the need for surgical intervention.

PMID- 17181628
TI  - Orbital cellulitis as a postoperative complication of sub-Tenon anaesthesia in
      cataract surgery.
AB  - Orbital cellulitis is a rarely reported sight-threatening complication of sub
      Tenon anaesthesia. We report a case of orbital cellulitis in a patient who had
      received sub-Tenon anaesthesia for routine cataract surgery. We discuss the
      potential under-reporting of complications of sub-Tenon anaesthesia that had a
      delayed presentation, and the possible association between the use of
      hyaluronidase in the anaesthetic mixture and orbital cellulitis following sub
      Tenon anaesthesia.

PMID- 17181629
TI  - Monitoring cataract surgery outcomes in Papua New Guinea.

PMID- 17181630
TI  - Assessment of clinical notes in Papua New Guinea.

PMID- 17181631
TI  - Targeting leukocyte trafficking to inflamed skin: still an attractive therapeutic
      approach?
AB  - Research into leukocyte trafficking and its therapeutic exploitation appears to
      be a multistep process, just like the trafficking cascade itself. The initial
      euphoria evoked by an early understanding of the trafficking steps was followed
      by considerable disappointment following the clinical failure of the first
      selectin antagonist Cylexin (CY-1503), a sialyl Lewis(X) mimetic. The research
      area recovered and identified additional attractive pharmacological targets such
      as chemokine receptors and integrins. However, after lack of efficacy in anti
      chemokine trials and the fatalities associated with anti VLA-4 therapy (Tysabri),
      the question arose again whether targeting leukocyte trafficking is really
      promising or whether such a complex, multistep process with many redundant and/or
      functionally overlapping molecules is simply too challenging to deal with. In
      this article, we delineate some pros and cons of this approach followed by a
      brief update on where we stand in the field and where we might move in the
      future.

PMID- 17181632
TI  - Frequency, function and CLA expression of CD4+CD25+FOXP3+ regulatory T cells in
      bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with
      autoantibodies to collagen XVII and tissue-separation along the dermo-epidermal
      junction. We addressed the question whether the loss of tolerance in BP patients
      is associated with a reduction and/or functional impairment of CD4+CD25+FOXP3+
      regulatory T cells, which are essential for the active maintenance of self
      tolerance. The relative and absolute frequency of CD4+CD25+ and CD4+CD25(high)
      regulatory T cells in the peripheral blood of newly diagnosed, untreated patients
      was similar to that of healthy controls. Interestingly, more than 50% of
      circulating CD4+CD25(high) regulatory T cells from both patients as well as
      healthy controls expressed cutaneous lymphocyte-associated antigen. Considerable
      numbers of FOXP3+ cells were detected in lesional skin of patients. CD4+CD25+
      regulatory T cells of patients were functionally intact as assessed by their
      ability to suppress allogeneic as well as antigen-specific T-cell proliferation.
      These data argue against a general defect of CD4+CD25+FOXP3+ regulatory T cells
      in patients with BP.

PMID- 17181633
TI  - Enhancement of cell migration by corticotropin-releasing hormone through ERK1/2
      pathway in murine melanoma cell line, B16F10.
AB  - Melanoma is a malignant skin cancer that displays a high rate of tumor cell
      migration and metastasis. This study examined how corticotropin-releasing hormone
      (CRH) affects the migration of melanoma cells in order to further understand the
      relationship between stress and tumor cell migration. The migration assay data
      showed that CRH treatment increased the level of B16F10 cell migration in a dose-
      and time-dependent manner. To determine whether the extracellular signal
      regulated protein kinase 1/2 (ERK1/2) signaling pathway is involved in the
      upregulation of melanoma migration, cells were pretreated with an inhibitor of
      ERK1/2 (PD098059). The pretreatment of PD098059 blocked the increase in cell
      migration. Furthermore, CRH induced the phosphorylation of ERK1/2. The maximum
      activation of ERK1/2 by CRH was observed at 15 min. Taken together, these results
      suggest that CRH is an important mediator that regulates the migration of
      melanoma cells in the skin during stress through the ERK1/2 signaling pathway.

PMID- 17181634
TI  - Early cutaneous gene transcription changes in adult atopic dermatitis and
      potential clinical implications.
AB  - Atopic dermatitis (AD) is a common pruritic dermatitis with macroscopically non
      lesional skin that is often abnormal. Therefore, we used high-density
      oligonucleotide arrays to identify cutaneous gene transcription changes
      associated with early AD inflammation as potential disease control targets. Skin
      biopsy specimens analysed included normal skin from five healthy non-atopic
      adults and both minimally lesional skin and nearby or contralateral non-lesional
      skin from six adult AD patients. Data were analysed on an individual gene basis
      and to identify biologically relevant gene networks. Transcription levels of
      selected genes were also analysed by quantitative PCR. Differential transcription
      occurring early in AD skin was indicated for (i) individual genes such as C-C
      chemokine ligand (CCL)18, CCL13, and interferon-alpha2 (IFNalpha2), (ii) genes
      associated with peroxisome proliferator-activated receptor (PPAR)alpha- and
      PPARgamma-regulated transcription, and possibly for (iii) immunoglobulin J-chain
      and heavy chain isotype transcripts. These data suggest that local changes in
      immunoglobulin-associated transcription may favour IgE over secretory
      immunoglobulin (multimeric IgM and IgA) expression in AD skin. Decreased PPAR
      activity appears common to both AD and psoriasis, and reduced cutaneous IFNalpha2
      transcription also appears characteristic of AD. Identification of these genes
      and pathways will direct future research towards controlling AD.

PMID- 17181635
TI  - Towards the development of a simplified long-term organ culture method for human
      scalp skin and its appendages under serum-free conditions.
AB  - Organ culture of human scalp skin is usually performed with serum-containing
      medium, which limits its analytical usefulness. Here we report that intact human
      scalp skin can be grown at the air/liquid interface in supplemented, serum-free
      William's E medium for more than 2 weeks. Active hair shaft growth was visible
      until day 16 and was significantly enhanced compared with minimum essential
      medium (MEM) + 10% fetal bovine serum (FBS). Moreover, William's E medium
      protected better against cell death than MEM + 10% FBS before day 12. Using
      quantitative immunochemistry, proliferating (Ki-67+) cells could still be
      observed in the epithelium of hair follicles even on day 17 of serum-free skin
      organ culture. The number of apoptotic (TUNEL+) cells in the skin epithelium rose
      steadily after day 5. Giemsa stains revealed mature skin mast cells even after 13
      days in culture. The percentage of surviving hair follicles (mostly with catagen-
      or telogen-like morphology) gradually increased over time displaying mostly
      catagen hair follicles after 17 days of culture. Although epidermis and hair
      follicle epithelium showed increasing atrophy and degeneration, and their
      pigmentation decreased gradually over time, some long-term-surviving epithelial
      islands were found in association with remnants of follicular structures as late
      as on day 88. These preliminary data suggest that a very simple serum-free organ
      culture method allows prolonged human skin and hair follicle survival as well as
      some limited hair follicle cycling in intact skin for more than 2 weeks under
      well-defined experimental conditions. This pragmatic assay invites multiple uses,
      and may become a valuable tool for both skin and hair research.

PMID- 17181636
TI  - What are subcutaneous adipocytes really good for?
AB  - Our acute awareness of the cosmetic, psychosocial and sexual importance of
      subcutaneous adipose tissue contrasts dramatically with how poorly we have
      understood the biology of this massive, enigmatic, often ignored and much-abused
      skin compartment. Therefore, it is timely to recall the exciting, steadily
      growing, yet underappreciated body of evidence that subcutaneous adipocytes are
      so much more than just 'fat guys', hanging around passively to conspire, at most,
      against your desperate attempts to maintain ideal weight. Although the subcutis,
      quantitatively, tends to represent the dominant architectural component of human
      skin, conventional wisdom confines its biological key functions to those of
      energy storage, physical buffer, thermoregulation and thermoinsulation. However,
      already the distribution of human superficial adipose tissue, by itself,
      questions how justified the popular belief is that 'skin fat' (which actually may
      be more diverse than often assumed) serves primarily thermoinsulatory purposes.
      And although the metabolic complications of obesity are well appreciated, our
      understanding of how exactly subcutaneous adipocytes contribute to extracutaneous
      disease - and even influence important immune and brain functions! - is far from
      complete. The increasing insights recently won into subcutaneous adipose tissue
      as a cytokine depot that regulates innate immunity and cell growth exemplarily
      serve to illustrate the vast open research expanses that remain to be fully
      explored in the subcutis. The following public debate carries you from the
      evolutionary origins and the key functional purposes of adipose tissue, via
      adipose-derived stem cells and adipokines straight to the neuroendocrine,
      immunomodulatory and central nervous effects of signals that originate in the
      subcutis - perhaps, the most underestimated tissue of the human body. The editors
      are confident that, at the end, you shall agree: No basic scientist and no doctor
      with a serious interest in skin, and hardly anyone else in the life sciences, can
      afford to ignore the subcutaneous adipocyte - beyond its ample impact on beauty,
      benessence and body mass.

PMID- 17181645
TI  - Telomeres rather than telomerase a key target for anti-cancer therapy?
AB  - It was in the 1930s that telomeres (from the Greek telos = end and meros = part)
      were first recognized as essential structures at the ends of the chromosomes and
      were shown to be important for chromosomal stability (Muller HJ: The remaking of
      chromosomes. The Collecting Net-Woods Hole 1938: 13: 181-198, McClintock B, The
      stability of broken ends of chromosomes in Zea mays. Genetics 1041: 26: 234-282).
      However, it was only in 1978 that the first telomeric sequence was identified --
      in the protocoa Tetrahymena, a single cell organism that at a certain stage of
      development has many identical minichromosomes with twice as many telomeres
      (Blackburn EH and Gall JG. A tandemly repeated sequence at the termini of the
      extrachromosomal ribosomal RNA genes in Tetrahymena. J. Mol. Biol. 1978: 120: 33
      53.). Today we know that telomeres form specialized, three-dimensional DNA
      protein structures and fulfil important capping functions. Besides, telomeric DNA
      is essential as ''access DNA'' for those cells that are not able to counteract
      loss of DNA during replication because they do not express telomerase, the enzyme
      responsible for telomere length maintenance. Since telomerase is mostly found in
      tumor cells and inhibition correlates with telomere shortening and finally growth
      inhibition, telomerase and lately also the telomeres themselves have become
      attractive targets for anti-cancer therapy. This review aims to critically throw
      light on different therapeutical approaches and comes to the conclusion that
      telomeres may be the better targets for cancer therapeutics.

PMID- 17181647
TI  - Gene expression and biomarkers in renal transplant ischemia reperfusion injury.
AB  - The incidence of postischemic acute renal allograft failure (ARF) occurs in
      roughly 25% of cadaveric donor kidney recipients. This high rate remained
      virtually unchanged over the last decades despite modification in recipient
      management and modern immunosuppressive strategies. It has recently been shown
      that among other reasons, the systemic inflammation in the brain death cadaveric
      organ donor contributes to subsequent ARF in the recipient. This review focuses
      on the consequences of ischemia and reperfusion on the cellular level and offers
      potential solutions for the reduction of ARF. Genome-wide gene expression
      analysis together with sophisticated biostatistical analysis made it possible to
      identify several candidate gene products and proteins that may act as specific
      and sensitive biomarker for renal inflammation and ischemia. These markers may be
      very helpful in the clinical management of patients with a high a priori risk of
      subsequent ARF such as recipients of marginal donor kidneys. Ongoing clinical
      trials will evaluate whether immunosuppression of the cadaveric organ donor
      before organ harvest will have the potential to reduce inflammation in the
      transplant kidney and subsequently lead to a reduction in the rate of ARF.

PMID- 17181648
TI  - From current immunosuppressive strategies to clinical tolerance of allografts.
AB  - In order to prevent allograft rejection, most current immunosuppressive drugs
      nonspecifically target T-cell activation, clonal expansion or differentiation
      into effector cells. Experimental models have shown that it is possible to
      exploit the central and peripheral mechanisms that normally maintain immune
      homeostasis and tolerance to self-antigens, in order to induce tolerance to
      alloantigens. Central tolerance results from intrathymic deletion of T cells with
      high avidity for thymically expressed antigens. Peripheral tolerance to nonself
      molecules can be achieved by various mechanisms including deletion of
      activated/effector T cells, anergy induction and active regulation of effector T
      cells. In this article, we briefly discuss the pathways of allorecognition and
      their relevance to current immunosuppressive strategies and to the induction of
      transplantation tolerance (through haematopoietic mixed chimerism, depleting
      protocols, costimulatory blockade and regulatory T cells). We then review the
      prospect of clinical applicability of these protocols in solid organ
      transplantation.

PMID- 17181649
TI  - No robust conclusions to be drawn from clinical trials in the absence of an
      adequate control group.

PMID- 17181650
TI  - 12-month safety and efficacy of everolimus with reduced exposure cyclosporine in
      de novo renal transplant recipients.
AB  - The proliferation signal inhibitor everolimus (Certican), has demonstrated
      efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized
      controlled studies were performed to compare 12-month efficacy and safety of
      everolimus 1.5 and 3.0 mg/day with reduced-dose CsA. Study 1 enrolled 237 de novo
      renal allograft recipients, randomizing 222 nonblack patients to either
      everolimus 1.5 or 3.0 mg/day, with the Neoral) dose guided by C(2) (monitoring of
      CsA concentration 2 h after dosing). Study 2 had a similar protocol, with
      basiliximab included, enrolling 256 recipients and randomizing 243 nonblack
      patients. In Study 1, there was a lower incidence of acute rejection in nonblack
      patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study
      2, the inclusion of basiliximab lowered the overall incidence of acute rejection;
      14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day)
      had acute rejection by 12 months (P =0.891). Renal function was preserved
      throughout the study, with no differences observed between groups within studies.
      Everolimus was well tolerated with no significant differences between doses.
      Everolimus, in combination with reduced-dose Neoral), demonstrated efficacy and
      was well tolerated. Basiliximab allows for utilization of lower doses of
      everolimus with reduced dosing of Neoral).

PMID- 17181652
TI  - Ligation of left renal vein for large spontaneous splenorenal shunt to prevent
      portal flow steal in adult living donor liver transplantation.
AB  - Persistance of a large spontaneous splenorenal shunt (SRS) may result in graft
      failure in adult living donor liver transplantation (LDLT) because it reduces the
      effective portal perfusion to the partial liver graft by diversion of
      hepatotrophic portal flow into this hepatofugal pathway. We performed a
      prospective study to evaluate the efficacy of ligation of left renal vein (LRV)
      to prevent portal flow steal and the safety of this procedure to the renal
      function in adult LDLT patients with SRS. Between October 2001 and January 2005,
      44 cirrhotic patients with large SRS underwent LDLT with ligation of LRV. Each
      patient received pre- and postoperative computed tomography and Doppler USG to
      assess the changes of collaterals and portal flow, as well as serial renal and
      liver function tests. Portal flow after ligation of LRV was statistically and
      significantly increased when compared with pre-operative value (P = 0.001).
      Whereas four patients (9.1%) demonstrated sustained, elevated serum creatinine
      levels after operation, the renal function tests returned to normal in 40
      patients. All patients recovered with satisfactory regeneration of the partial
      liver graft and there was no procedure-related permanent renal dysfunction. In
      conclusion, ligation of LRV to prevent a 'portal steal phenomenon' seems to be a
      safe and effective graft salvage procedure for large spontaneous SRS (>10-mm
      diameter) in adult LDLT.

PMID- 17181651
TI  - The clinical significance of early histological rejection with or without
      biochemical abnormality in adult living donor liver transplantation for hepatitis
      B virus related end stage liver disease.
AB  - There is no agreement regarding the treatment of early allograft rejection (EAR)
      in adult living donor liver transplantation (LDLT). A protocol biopsy was
      performed in 62 adult LDLT recipients. Twenty-one patients (33.9%) had
      histological evidence of EAR. Of these, 14 patients had biochemical abnormalities
      and seven patients had no associated biochemical abnormalities. None of the seven
      patients with subclinical EAR (11.3% of the entire study population) were
      treated, and no subsequent rejection was observed. Gender mismatch (female-to
      male) was the single independent risk factor for histological EAR [odds ratio
      (OR) = 13.458; 95% confidence interval (CI), 1.836-98.649] and the cumulative
      probability for a subsequent rejection was higher in patients with EAR (OR =
      11.085; 95% CI, 1.221-100.654). However, the actuarial 1 year patient and graft
      survival rate in patients with EAR (81.0% and 85.5%) were similar to those
      without EAR (92.7% and 97.25%; P = 0.127 and 0.302, respectively). The presence
      of an initial biochemical abnormality was an independent risk factor for both a
      decreased patient survival (OR = 5.827; 95% CI, 1.095-31.017; P = 0.039) and
      graft loss (OR = 20.646; 95% CI, 2.044-208.524; P = 0.010). Subsequent rejection
      developed more frequently in patients with EAR. However, the survival is not
      determined by the presence of EAR but by the presence of a biochemical
      abnormality.

PMID- 17181653
TI  - Group milleri streptococci: significant pathogens in solid organ recipients.
AB  - Group milleri streptococci (GMS) comprise a heterogeneous group of streptococci
      including the species intermedius, constellatus and anginosus. They may cause
      chronic intra-abdominal and intrathoracic abscesses, which are difficult to
      treat. This is a retrospective analysis including 45 transplant recipients in
      whom GMS were isolated. The epidemiology, clinical significance and the impact on
      the outcome in all transplant patients with infections caused by GMS during a 4
      year period (2001-2004) was evaluated. The 45 solid organ recipients (88
      isolates) included 34 liver-, four kidney/pancreas-, one kidney-, two small bowel
      , three combined liver/kidney- and one combined kidney/small bowel transplant
      recipient. In 42 cases GMS caused intra-abdominal infection, in two cases pleural
      empyema and in one case soft tissue infection. Only a single isolate of GMS was
      cultured from blood. In 54 of the 88 specimens (61%), which grew GMS, other
      pathogens were also isolated. GMS frequently caused recurrent cholangitis (n =
      17) associated with anastomotic and nonanastomotic biliary strictures. These
      cases were managed by repeated stenting or surgical intervention and prolonged
      antibiotic therapy. No patient died directly related to GMS infection and all
      except one case responded to combined surgical/antibiotic treatment. One pancreas
      graft was lost because of erosion haemorrhage associated with an abscess. GMS
      were susceptible to penicillin G, carbapenems and clindamycin, whereas
      cephalosporins and quinolones showed intermediate activity or resistance in some
      cases, and GMS in general were found resistant to aminoglycosides. GMS may cause
      serious infections in transplant recipients which are difficult to treat. Their
      prevalence in transplant surgical site infections thus far may have been
      underestimated.

PMID- 17181654
TI  - Incidence and risk factors for the development of lung tumors after liver
      transplantation.
AB  - Tobacco and immunosuppression are risk factors for developing upper aerodigestive
      and lung tumors after transplantation. This study comprises 701 adult recipients
      who survived more than 2 months after transplant: 276 patients underwent
      orthotopic liver transplantation (OLT) for alcoholic cirrhosis (AC) and 425 for
      nonalcoholic disease. The aim is to analyze the incidence, clinical
      characteristics, risk factors, and outcome of patients who develop lung
      malignancies after OLT. Incidence of lung cancer was 2.1% (15 patients): 4.3% (12
      patients) in the alcoholic group and 0.7% (three patients) in the nonalcoholic
      group (P < 0.001). Mean time from OLT to tumor diagnosis was 86 months. Thirteen
      patients were smokers; 12 patients were heavy drinkers; and 11 were drinkers and
      smokers. Squamous cell carcinoma was diagnosed in nine patients, large cell
      carcinoma in three, adenocarcinoma in two, and broncoalveolar in one. Tumor
      staging: 10 patients at stage IV; three at stage IIIB; and two at stage IIB.
      Tumor resection was performed in one patient, and three also received
      chemotherapy. Mean survival after tumor diagnosis was 5.4 months. There is a
      higher risk of lung cancer in smoker patients who have undergone OLT for AC, and
      have a very poor prognosis because tumors are diagnosed at advanced stages.

PMID- 17181656
TI  - Risk factors and treatment of hemorrhagic cystitis in children who underwent
      hematopoietic stem cell transplantation.
AB  - A retrospective cohort of 163 children with 171 hematopoietic stem cell
      transplantation (HSCT) performed during Mar. 1992-Dec. 2005 were analyzed to
      evaluate the incidence, risk factors, management, and outcome of hemorrhagic
      cystitis (HC). Fourteen patients (8.2%) developed HC (6 boys, median age 6.6
      years) at 0-166 days after HSCT (median 25 days), and lasted for 3-96 days
      (median 26 days). Older age at transplant (median 11.0 vs. 6.4 years, P = 0.013),
      allogeneic transplant (OR = 4.4, P = 0.02), cyclophosphamide-containing
      conditioning (OR = 4.87, P = 0.008), moderate-to-severe acute graft-versus-host
      disease (GVHD) (OR = 3.56, P = 0.025) and hepatic GVHD (OR = 3.62, P = 0.017)
      were associated with higher risks of HC in univariate but not multivariate
      analyses. While estrogen was ineffective in most patients, intravesical formalin,
      which was used in five patients, was found to be a very effective yet safe
      treatment for intractable HC. Patients with HC had longer hospital stay (median
      175 vs. 88 days, P = 0.004). HC resolved after treatments in all cases but eight
      of the 14 patients subsequently died of other complications of HSCT. In
      conclusion, HC is a serious complication of allogeneic HSCT. Treatment with
      intravesical formalin appears effective and safe and can be considered early in
      severe HC to reduce the risk of morbidity and mortality.

PMID- 17181655
TI  - Estimated donor glomerular filtration rate is the most important donor
      characteristic predicting graft function in recipients of kidneys from live
      donors.
AB  - We hypothesized that predictors of outcome in live donor transplants were likely
      to differ significantly from deceased donor transplants, in which cold ischaemia
      time, cause of donor death and other donor factors are the most important
      predictors. The primary aim was to explore the independent predictors of graft
      function in recipients of live donor kidneys (LDK). Our secondary aim was to
      determine which donor characteristics are the most useful predictors. A
      retrospective analysis was undertaken of all patients receiving live donor (n =
      206) renal transplants at our institution between 31 May 1994 and 15 October
      2002. Twelve patients were excluded from the analysis. Follow-up was completed on
      all patients until graft loss, death or 22 November 2003. We explored predictors
      of Nankivell glomerular filtration rate (GFR) at 6 months by multivariate linear
      regression. In the 194 patients studied, the mean recipient 6-month Nankivell GFR
      was 59 +/- 15 ml/min/1.73 m(2). Independent predictors of recipient GFR in at 6
      months were donor Cockcroft-Gault GFR (CrCl; beta 0.16; CI 0.13 to 0.29; P <
      0.0001), steroid resistant rejection (beta-6.07; CI -12.05 to -0.09; P = 0.006)
      and delayed graft function (DGF) (beta-10.0; CI -19.52 to -0.49; P = 0.039).
      Renal function in an LDK transplant recipients is predicted by donor GFR,
      episodes of steroid resistant rejection and DGF. Importantly, donor Cockcroft
      Gault GFR is the most important characteristic for predicting the recipient renal
      function.

PMID- 17181657
TI  - Inflammation and endothelial activation are linked to renal function in long-term
      kidney transplantation.
AB  - The aim of this study was to investigate the relationships between inflammation
      and adhesion molecules in long-term kidney transplantation. We measured serum
      concentrations of tumor necrosis factor-alpha (TNFalpha) and intercellular and
      vascular cell adhesion molecules (ICAM-1 and VCAM-1) in 35 renal transplant
      recipients (mean age of transplantation 5 +/- 3 years) and in 35 chronic renal
      insufficiency (CRI) patients; twenty-six healthy subjects were enrolled as
      controls. Transplanted showed higher values than controls of TNFalpha (P <
      0.0001), ICAM-1 (P < 0.0001), and VCAM-1 (P < 0.0001). CRI group as well
      exhibited higher concentrations than controls of TNFalpha (P < 0.0001), ICAM-1 (P
      < 0.0001), and VCAM-1 (P < 0.0001). Transplanted and CRI patients had similar
      blood pressure and renal function levels, and TNFalpha, ICAM-1, and VCAM-1 were
      not significantly different in the two groups. In transplanted group ICAM-1, VCAM
      1, and TNFalpha correlated negatively and independently with glomerular
      filtration rate (GFR) -P < 0.00001 for all. TNFalpha as well correlated with ICAM
      1 and VCAM-1 (P < 0.001, respectively). In CRI group, TNFalpha correlated with
      serum creatinine, ICAM-1, and VCAM-1 (P = 0.01 for all). In conclusion, in long
      term renal transplantation, the level of kidney function and both inflammation
      and endothelial activation are closely related. In fact, the multiple regression
      analysis demonstrated that the level of kidney insufficiency and the levels of
      the studied molecules were independently associated.

PMID- 17181658
TI  - Static normothermic preservation of renal allografts using a novel nonphosphate
      buffered preservation solution.
AB  - The aim of this study was to assess the viability and function of renal
      allografts under normothermic conditions using a novel nonphosphate buffered
      preservation solution AQIXRS-I. Porcine kidneys were flushed at 30 degrees C with
      AQIXRS-I at 100 mmHg pressure after 5-10 min warm ischaemic time and stored
      statically at either 4 degrees C or 30 degrees C for 2 h (n = 6 per group).
      Assessment of renal function by physiological and biochemical parameters was
      performed by perfusing the organs with autologous blood at 37 degrees C, with an
      initial circulating serum creatinine concentration of 1000 mumol/l on an isolated
      organ perfusion system for 6 h. Although the hypothermic group demonstrated
      overall superior renal function, the normothermic stored kidneys displayed a
      statistically comparable acid-base balance (7.37 +/- 0.15 vs. 7.3 +/- 0.09, P =
      0.24). Furthermore, renal function was still evident after 6 h perfusion with
      increasing oxygen consumption, renal blood flow and reduced renal vascular
      resistance. The effectiveness and versatility of AQIXRS-I as a preservation
      solution under both normothermic and hypothermic conditions has been
      demonstrated. Renal viability was maintained after 2 h static normothermic
      storage. This study provides a foundation for further analysis utilizing
      normothermic preservation.

PMID- 17181659
TI  - Protective effect of adenosine A2A receptor activation in small-for-size liver
      transplantation.
AB  - The aim of the present study was to investigate the potential role of adenosine
      A(2A) receptor (A(2A)R) activation in small-for-size liver transplantation. A rat
      orthotopic liver transplantation model was performed by using 40% (range: 36-46%)
      liver grafts. Recipients were given either saline (control group) or CGS 21680 (2
      p-(2-Carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride, a
      selective A(2A)R agonist), or CGS 21680+ ZM 241385 (a selective A(2A)R
      antagonist) immediately after reperfusion for 3 h. Compared with control group,
      CGS 21680 used at both low dose (0.05 microg/kg/min) and high dose (0.5
      microg/kg/min) increased the survival rate from 16.7% (2/12) to 83.3% (10/12) and
      66.7% (8/12), respectively. These effects correlated with improved liver function
      and preserved hepatic architecture. CGS 21680 effectively decreased neutrophil
      infiltration, suppressed pro-inflammatory (TNF-alpha, IL-1beta and IL-6)
      expression, promoted expression of antiapoptotic molecules, and inhibited
      apoptosis. The effects of CGS 21680 were prevented when ZM 241385 was co
      administrated. In conclusion, the present study showed that A(2A)R activation
      alleviated portal hypertension, suppressed inflammatory response, reduced
      apoptosis, and potentiated the survival of small-for-size liver grafts. Our
      findings provide the rationale for a novel therapeutic approach using A(2A)R
      activation to maximize the availability of small-for-size liver grafts.

PMID- 17181660
TI  - Successful treatment of recurrent focal segmental glomerulosclerosis after kidney
      transplantation by plasmapheresis and rituximab.
AB  - A 22-year-old patient whose primary kidney disease was focal segmental
      glomerulosclerosis (FSGS) developed severe recurrence of proteinuria (up to 57
      g/24 h) immediately after a haploidentic living donor kidney transplantation
      despite pre-operative plasmapheresis. The immunosuppressive treatment consisted
      of tacrolimus, mycophenolate mofetil, basiliximab and steroids. He underwent 10
      plasmapheresis sessions in the first 3-week post-transplantation. In addition, he
      received 2 i.v. doses of rituximab (RTX) 600 mg (375 mg/m(2)) on days 7 and 15.
      Proteinuria decreased below nephrotic range at day 14 and serum creatinine
      returned progressively to normal values. A short course of oral ciclophosphamide
      (100 mg/j) was administrated between days 22 and 40 and three additional
      plasmapheresis sessions on days 34, 39 and 49. This strategy allowed obtaining
      sustained full remission of the nephrotic syndrome (NS) and excellent graft
      function, which persists over 2 years after transplantation. No notable adverse
      events related to RTX or plasmapheresis were observed. This case suggests that
      RTX associated with plasmapheresis may be an effective treatment of recurrent NS
      because of FSGS.

PMID- 17181662
TI  - Meta-analysis of the effects of respiratory rehabilitation programmes on exercise
      capacity in accordance with programme characteristics.
AB  - AIMS AND OBJECTIVES: This study was performed to investigate the effects of
      respiratory rehabilitation programmes on exercise capacity in terms of the
      programme type, the protocol used and other programme characteristics.
      BACKGROUND: As the suitable rehabilitation programmes have not been specified,
      diverse programmes are provided in clinics. DESIGN: Meta-analysis of the primary
      study results. METHODS: A computerized search through MEDLINE and CINHAL in
      addition to tracking down references cited in bibliographies of primarily
      searched studies were performed to obtain sample studies. Finally 19 research
      reports were examined. RESULTS: The results of meta-regression showed that the
      combined effect size of the programmes on exercise capacity was unaffected by
      forced expiratory volume (in one second), age, the duration and frequency of the
      programme, or study quality. In addition, the results of meta-anova indicated
      that the combined effect size was not affected by (i) whether a programme was
      hospital based or not, (ii) whether a programme was lower-extremity or combined
      low- and upper-extremity exercise training, (iii) measurement time, and (iv)
      exercise intensity. CONCLUSIONS: The effects of programmes on exercise capacity
      were not differed in terms of the places where rehabilitation programmes were
      applied, programme content, measurement time, exercise target sites of body, and
      the duration and frequency of the programme. RELEVANCE TO CLINICAL PRACTICE: The
      results of the present study can provide objective data when constructed or
      applied on a respiratory rehabilitation programme in clinics.

PMID- 17181663
TI  - A review of the use of insulin protocols to maintain normoglycaemia in high
      dependency patients.
AB  - AIM: This paper critically examines the evidence base for and issues involved in
      the introduction of an insulin protocol to maintain normoglycaemia in patients
      within a medical/surgical high dependency ward. BACKGROUND: A growing body of
      evidence has linked hyperglycaemia to worsened clinical outcomes. This has led to
      intravenous insulin protocols becoming a new standard of care in intensive care
      units. However, the use and benefits of insulin protocols within high dependency
      units have not yet been addressed in the literature. METHODS: The literature was
      examined for the 10-year period up to January 2005. The databases searched were
      MEDLINE, OVID, CINHAL, the British Nursing Index, the EBSCO collection, the
      COCHRANE library, the Department of Health, and guidelines within the Scottish
      Intercollegiate Guidelines Network and National Institute for Clinical Excellence
      using the key words insulin, protocol, hyperglycaemia, critical care, intensive
      care and high dependency. RESULTS: The literature reports that both medical and
      surgical intensive care patients treated with intravenous insulin protocols to
      maintain normoglycaemia experienced significantly reduced mortality and
      morbidity. Resulting hypoglycaemic episodes were limited with no incidence of
      patient deterioration. A review of published intravenous insulin protocols used
      in intensive care settings revealed their safe and effective use in nurse to
      patient ratios similar to those present in high dependency units. CONCLUSIONS: In
      the light of this evidence, it would seem safe and ethically correct to enable
      high dependency patients to benefit from this cheap intervention. An insulin
      protocol tailored for the glycaemic control of high dependency patients has been
      suggested, although it may have to be commenced in conjunction with other fluid
      and nutrition protocols to safeguard the risk of hypoglycaemic events. Further
      research into the safety and benefit of insulin protocols in high dependency
      populations is required. RELEVANCE TO CLINICAL PRACTICE: The stress of critical
      illness often leads to hyperglycaemia, which is linked to worsened clinical
      outcomes. Both medical and surgical intensive care patients treated with
      intravenous insulin protocols to maintain normoglycaemia experienced
      significantly reduced mortality and morbidity. This paper identifies that, to
      date, no research into the benefits of glycaemic control in high dependency
      populations has been published. The case for the introduction of insulin
      protocols into high dependency units is therefore examined and an insulin
      protocol suggested.

PMID- 17181664
TI  - Review of advanced nursing practice: the international literature and developing
      the generic features.
AB  - AIM: The aim of this article is to review the nursing literature on the notion of
      advanced nursing practice (ANP) and consequently provide clarifications on the
      concept of advanced nurse practitioner by developing its' generic features.
      BACKGROUND: This paper commences by critically reviewing the concept of advanced
      nursing practice as it is portrayed within the literature. From this review, a
      series of contradictions emerged in terms of definitions and roles. On further
      analysis of the literature the core aims and goals of the ANP are revealed.
      METHODS: An informative and narrative systematic literature review was
      undertaken, using specific inclusion and exclusion criteria. The mass of
      retrieved material was carefully screened and methods of data saturation were
      used. Consequently, the material was read, re-read and indexed as to develop
      seven thematic units that formed the generic features of the ANP. FINDINGS: The
      generic features that emerged are: (i) the use of knowledge in practice, (ii)
      critical thinking and analytical skills, (iii) clinical judgement and decision
      making skills, (iv) professional leadership and clinical inquiry, (v) coaching
      and mentoring skills, (vi) research skills and (vii) changing practice.
      CONCLUSION: Reviewing the literature on the concept of ANP, a great variety of
      definitions, conceptualizations and roles emerged. Nonetheless, on a closer
      reading, a common goal was identified, which was the attainment of practice and
      professional autonomy via ANP roles for enhanced practice provision. Eventually,
      from the reviewed literature, seven generic features of the ANP were developed,
      thus providing clarification to the role and the characteristics of the ANP.
      RELEVANCE TO CLINICAL PRACTICE: Clarifying the confusion surrounding advanced
      nursing practice and gaining an in-depth understanding of its' generic features
      would facilitate practitioners, practice educators and clinical managers to
      develop those skills that would allow them or their staff or students to practise
      at an advanced level.

PMID- 17181665
TI  - Health promotion model for childhood violence prevention and exposure.
AB  - AIMS AND OBJECTIVES: To discuss the Health Promotion Model for Violence
      Prevention and Exposure and intervention strategies for implementation.
      BACKGROUND: Violence causes physical and psychosocial harm to children. Because
      little collaboration exists between specialties in the USA, a model that
      incorporates both a public health and psychosocial approach is needed to assess
      the risk for exposure to violence and the effects of violence as well as
      developing prevention strategies. Prevention and intervention includes primary,
      secondary and tertiary levels that focus on either the community or individual.
      However, primary and secondary prevention, such as anticipatory guidance and
      screening, can be implemented by both community and primary care nurses. METHODS:
      A review of the literature and on-line resources focusing on children's exposure
      to violence provided the basis for discussion of the commonalities and
      differences between the public health and psychosocial approach to assessing,
      preventing and intervening with children exposed to violence. This discussion led
      to the development of the proposed model. CONCLUSIONS: This model can identify
      more children at risk for social, physical and psychological harm because of
      exposure to violence. Implementing prevention or treatment interventions can
      decrease the impact of violence on children. RELEVANCE TO CLINICAL PRACTICE: This
      model can be implemented by public health, psychiatric and primary care nurses by
      incorporating the model into the well-child exam, school screenings and after
      school programs. Collaboration between specialties will increase referrals for
      participation in anti-violence programs or treatment interventions.

PMID- 17181666
TI  - A systematic review of predictors and screening instruments to identify older
      hospitalized patients at risk for functional decline.
AB  - AIMS AND OBJECTIVES: To determine a valid, reliable and clinical user-friendly
      instrument, based on predictors of functional decline, to identify older patients
      at risk for functional decline. The predictors of functional decline are
      initially considered and, subsequently, the characteristics and psychometric
      qualities of existing screening instruments are investigated. BACKGROUND:
      Functional decline is a common and serious problem in older hospitalized
      patients, resulting in a change in quality of life and lifestyle. Studies have
      shown that 30-60% of older people develop new dependencies in activities of daily
      living (ADL) during their hospital stay. Adverse health outcomes such as
      mortality, a prolonged hospital stay, nursing home placement and increased
      dependency of older people at home are the results. Not only are the personal
      costs high but also, in a rapidly growing older population, the impact on health
      care costs is also high. RESULTS: Age, lower functional status, cognitive
      impairment, preadmission disability in instrumental activities of daily life
      (IADL), depression and length of hospital stay were identified as predictors of
      functional decline. Three screening instruments to identify hospitalized patients
      at risk for functional decline were found in the literature: the Hospital
      Admission Risk Profile, the Identification of Seniors at Risk and the Care
      Complexity Prediction Instrument. The reported validity was moderate. Reliability
      and the ease of use in the clinical setting were not well described. CONCLUSION:
      These three instruments should be further tested in a hospitalized older
      population. RELEVANCE TO CLINICAL PRACTICE: Screening is a first step to identify
      patients at risk for functional decline and this will make it possible to treat
      patients who are identified so as to prevent functional decline. Because of their
      ability to observe and to guide the patients and the overall view they have,
      nurses play a key role in this process.

PMID- 17181667
TI  - Review of effective advanced cardiac life support training using experiential
      learning.
AB  - AIMS AND OBJECTIVES: This paper examines issues of contention regarding current
      practices and suggests the application of the experiential theory of learning
      (incorporating reflective practice) to advanced cardiac life support (ACLS)
      training. BACKGROUND: The need for formalized training in cardiopulmonary
      resuscitation (CPR) and ACLS is well documented. However, the effectiveness of
      traditional training programmes has not been firmly established. The question
      still remains - how to best ensure transfer of learning enabling learners to
      apply classroom knowledge successfully in the clinical setting. It is argued that
      educators can no longer rely on traditional teaching methods and more effective
      learner-centred education techniques are required. METHOD: A review of available
      literature regarding ACLS training has been conducted for this discussion. DATA
      SOURCES AND SELECTION: MEDLINE, CINAHL, OVID, Expanded Academic and Proquest were
      searched using textwords. English-language articles related to CPR and ACLS
      practices and also experiential learning were reviewed. Additional references
      were also reviewed from the bibliographies and from citation searches on key
      articles. Articles related to CPR/ACLS and experiential learning practices
      published within the last 10 years were reviewed. RESULTS: There is evidence that
      past ACLS training programmes have proven inconsistent and inadequate, with
      numerous studies reporting trainees have poor retention; and, therefore,
      ineffective ACLS skills as a result. CONCLUSIONS: The reviewed literature
      demonstrates that the need for effective ACLS training is clear. Increasing
      numbers of critically ill patients in hospitals means that it has never been more
      important to ensure the competence of healthcare professionals. Training must
      give learners a chance to pull together all aspects of ACLS and the use of
      experiential learning has the potential to achieve this aim. RELEVANCE TO
      CLINICAL PRACTICE: It is argued that providing training designed and implemented
      using experimental learning enhances learning through critical thinking and
      reflection, and subsequently should improve ACLS outcomes.

PMID- 17181668
TI  - Nitric oxide and nursing: a review.
AB  - AIMS AND OBJECTIVES: This paper, therefore, aimed to review published literature
      in this area of pharmacological exploitation, to look at the therapeutic
      applications and clinical relevance and, by so doing, provide an accessible
      source for nurses to gain insight into the role of nitric oxide in the clinical
      setting. BACKGROUND: Nitric oxide is a chemical mediator fundamental in the
      maintenance of adequate tissue perfusion and effective cardiovascular function; a
      major endogenous regulator of vascular tone. The use of nitrates are well
      established as pharmacological agents but it is only recently that it has been
      recognized that they act as a source of nitric oxide. Although widely addressed
      within the medical literature, there appears to be a paucity of nursing
      literature that explores either its physiological action, or its relevance to
      nursing practice. CONCLUSIONS: This literature review provides an overview of the
      use of nitric oxide and its implications for nursing practice and patient
      outcomes. RELEVANCE TO CLINICAL PRACTICE: Knowledge of nitric oxide and its
      action is pertinent to nurses across diverse specialities. It helps in
      understanding the principles of many nitrogen-derived medications which nurses
      administer to their patients on a daily basis. In terms of oral medication, this
      is demonstrated by greater insights into the action of nitrates, the appreciation
      of surprising developments in medications such as sildenafil and the development
      of new drug opportunities such as nitric oxide-non-steroidal anti-inflammatory
      drugs. Equally, the use of inhaled nitric oxide therapy in adult and neonatal
      critical care units appears to be an increasingly valuable source of treatment. A
      particular research challenge is found in the attempt at nitric oxide inhibition
      in the management of septic shock. The authors argue that understanding such
      esoteric areas of therapeutic developments is increasingly to be part of the
      repertoire of knowledge and skills for nurses in the 21st century.

PMID- 17181669
TI  - A review of the literature on atrial fibrillation: rate reversion or control?
AB  - AIMS: The aim of this paper is to review the current literature describing the
      aetiology of atrial fibrillation and to examine the evidence for rate reversion
      and rate control. BACKGROUND: Atrial fibrillation is the most commonly seen
      arrhythmia within the clinical setting. Treatment depends on severity of
      symptoms, which are predominantly palpitations and shortness of breath. The
      primary complications from atrial fibrillation are thrombo-embolic events (such
      as a pulmonary embolus or stroke). OBJECTIVES AND METHODS: A comprehensive
      literature review on atrial fibrillation, rate reversion and rate control was
      undertaken to examine the incidence of atrial fibrillation, to review research on
      management of atrial fibrillation and to determine if rate reversion was superior
      to rate control in the treatment of atrial fibrillation. RESULTS: Many studies
      have been carried out to determine the best treatment for this condition. The
      choices are currently pharmacological and electrical cardioversion in conjunction
      with anticoagulant therapy. Drug therapies are not without their problems,
      especially toxicity and the need for close clinical monitoring. Transaesophageal
      echocardiography has been used to establish the presence of left atrial thrombi
      and aims to reduce the anticoagulation time and reduce the risk of thrombo
      embolic events. A randomized comparative study of transaesophageal
      echocardiography and conventional anticoagulation therapy prior to cardioversion
      demonstrated statistically significant reduction in haemorrhagic events and a
      shorter time to cardioversion in those in the transaesophageal echocardiography
      group compared with the conventional group. For those with persistent atrial
      fibrillation, surgery is an option with valve repair or replacement carried out
      in conjunction with a bi-atrial surgical ablation. CONCLUSIONS: The management of
      atrial fibrillation is dependent on many factors and to date there are no proven
      clinical rationale for rate control or reversion. RELEVANCE TO CLINICAL PRACTICE:
      Atrial fibrillation requires immediate attention in order to avoid thrombo
      embolic complications and the use of transaesophageal echocardiography and
      conventional anticoagulation therapy can significantly reduce these
      complications.

PMID- 17181670
TI  - Postoperative pain in older people: a review of the literature.
AB  - AIMS AND OBJECTIVES: The literature review was conducted to explore those factors
      which complicate pain management in older people to inform future research,
      education and nursing practice in this area. BACKGROUND: Acute pain management in
      hospitalized older people is complex because of the physiological changes of
      ageing, pharmacological factors and under-representation of this patient group in
      reported research about assessing acute pain. METHODS: A review of the literature
      was undertaken using electronic databases and specified search terms, some hand
      searching was also used and included the grey literature, textbooks and
      conference proceedings. A computerized literature search was carried out using
      CINAHL, Bandolier, Cochrane, Medline, the British Nursing Index and the
      International Association for the Study of Pain website for the period 1992-2004.
      The search terms were acute pain, older people, elder care, pain assessment and
      acute pain services. Thirty-seven research-based reviews and published studies
      and 17 policy documents were included. CONCLUSIONS: Managing acute pain well in
      older adults involves understanding the influence of a series of integrated
      factors: attitudes and beliefs, physiological ageing processes, pharmacological
      factors and the social construction of the older person in healthcare contexts.
      RELEVANCE TO CLINICAL PRACTICE: This review offers new insight into those factors
      which, taken together, add complexity to managing acute pain in older people
      well. Moreover, nurses are the professional group mainly responsible for
      assessing pain, administering and now prescribing analgesia and evaluating the
      quality of pain relief in older people. On this basis, they are also the group
      most likely to effect improved patient outcomes.

PMID- 17181671
TI  - Rectal suppository insertion: the reliability of the evidence as a basis for
      nursing practice.
AB  - AIMS AND OBJECTIVES: This paper considers the correct method for inserting a
      rectal suppository, both as a medication and also to achieve bowel evacuation.
      The aim is to find out whether the correct method is blunt end or pointed end
      foremost. BACKGROUND: It follows from a question raised by a third year student
      nurse. In the classroom, she had been taught that the correct method for the
      administration of a suppository for systemic absorption was to insert it blunt
      end foremost into the rectum. However, if the suppository was to be used for
      evacuant purposes, it should be given pointed end foremost. In clinical practice,
      however, she was told the suppository should always be inserted pointed end
      foremost in all cases, whatever the purpose. DESIGN: This article seeks to
      clarify the dilemma by examining the sources of evidence underpinning different
      methods for inserting a rectal suppository. Hence, the literature on the
      insertion of rectal suppositories was gathered as systematically as possible from
      medical journals and textbooks, nursing journals and textbooks and manufacturers'
      information to patients. METHOD: Having gathered the literature, this was
      examined, appraised and critically analysed for rigour, coherence and
      reliability. RESULTS: The review of the literature appears to show that evidence
      adduced for inserting the suppository blunt end foremost derives from one study
      published in the Lancet in 1991, which challenged 'commonsense'. There did not
      appear to be other, more recent research. On the other hand, manufacturers'
      information to patients states generally that the suppository should be inserted
      pointed end foremost. This has direct relevance for the administration of
      suppositories and also raises questions as to how research may become integrated
      into healthcare practice without adequate justification. CONCLUSIONS: An article
      published in the Lancet in 1991 has had a fundamental effect on nursing practice,
      but has not been subject to scrutiny. The advice given in this Lancet article
      differs from that currently given by most manufacturers of suppositories, which
      involves the terms of their product licence. Hence, there is a potential for
      problems with legal liability should an untoward event arise. RELEVANCE TO
      CLINICAL PRACTICE: Inserting rectal suppositories, whether as a medication or to
      achieve bowel evacuation, is a very common healthcare practice. Currently, there
      is inconsistency and discrepancy in the correct method for this procedure in both
      nursing education and practice. This paper examines the reliability of existing
      evidence and shows the need for further work in order to provide a reliable
      evidence base for this commonplace clinical procedure.

PMID- 17181672
TI  - A review of the benefits of whole body exercise during and after treatment for
      breast cancer.
AB  - AIM: A current critical review of the literature was deemed necessary to evaluate
      the strength of evidence to inform clinical practice. BACKGROUND: Recently, there
      has been a noticeable increase in empirical literature surrounding the benefits
      of exercise for breast cancer patients. METHODS: A systematic search strategy was
      used to identify relevant literature. Twenty-nine articles were retained for
      critical review, appraised for quality and synthesized. RESULTS: Many early
      studies had limited internal and external validity. Recent studies were
      considerably more rigorous and robust. Consistent support for all types of
      aerobic exercise was most evident in studies of patients during adjuvant cancer
      treatments (chemotherapy and radiotherapy), compared with post-treatment studies.
      The evidence which suggested that aerobic exercise limits cancer-related fatigue
      was particularly strong. For other patient concerns, the empirical support was
      less robust, however, the potential for beneficial and measurable patient
      outcomes was indicated for cardiopulmonary function, overall quality of life,
      global health, strength, sleep, self-esteem and reduced weight gain, depression,
      anxiety and tiredness. CONCLUSIONS: Additional studies with higher methodological
      quality are required in this clinically relevant area to substantiate current
      indications particularly for patient subgroups (e.g. older people, those with
      advanced cancer and the disadvantaged). RELEVANCE TO CLINICAL PRACTICE: It is
      important for all healthcare professionals involved in the care of individuals
      affected by breast cancer to be aware of the evidence surrounding the benefits of
      exercise and to encourage patients to increase physical activity and improve
      their overall health and well-being.

PMID- 17181673
TI  - A review of the impact and effectiveness of nurse-led care in dermatology.
AB  - AIMS AND OBJECTIVES: To identify systematically, summarize and critically
      appraise the current evidence regarding the impact and effectiveness of nurse-led
      care in dermatology. BACKGROUND: A diverse range of nurse-led models of care
      exist in dermatology. Primary studies have been conducted evaluating these
      models, but review and synthesis of the findings from these studies have not been
      undertaken. METHOD: Systematic searches of CINAHL, MEDLINE, British Nursing Index
      (BNI) and the RCN Library Catalogue from 1990 until March 2005. The searches were
      supplemented by an extensive hand search of the literature through references
      identified from retrieved articles and by contact with experts in the field.
      RESULTS: Fourteen relevant publications were identified and included findings
      from both primary and secondary care. The evidence indicates that nurses are
      treating a number of dermatological conditions, primarily using treatment
      protocols, across a broad range of clinical settings. However, some nurses
      working in primary care, lack confidence to treat some of these conditions and
      the educational needs of these nurses are frequently unmet. A reduction in the
      severity of the condition and more effective use of topical therapies are
      benefits of nurse interventions on service delivery. Faster access to treatment,
      a reduction in referrals to the general practitioner or dermatologist and an
      increase in knowledge of their condition are benefits reported by patients.
      CONCLUSIONS: Findings of the review are generally positive. However, there are
      methodological weaknesses and under researched issues, e.g. cost effectiveness of
      nurse-led care and the prescription of medicines by nurses for patients with
      dermatological conditions that point to the need for further rigorous evaluation.
      RELEVANCE TO CLINICAL PRACTICE: Nurse-led care is an integral element of the
      dermatology service offered to patients. This review highlights the impact of
      this care and the issues that require consideration by those responsible for the
      development of nurse-led models of care in dermatology.

PMID- 17181675
TI  - The effect of different body positions on blood pressure.
AB  - AIM: The aim of the present study was to test the effects of different body on BP
      readings in a Turkish healthy young adults. BACKGROUND: It is known that many
      factors influence an individual's blood pressure measurement. However,
      guideliness for accurately measuring blood pressure inconsistently specify that
      patient's position and they should keep feet flat on the floor. Although there
      are more information on arm position in blood pressure measurement, surprisingly
      little information can be found in the literature with respect to the influence
      of body position on the blood pressure readings in healthy young people. METHODS:
      A total of 157 healthy young students who had accepted to participate in the
      study were randomly selected. In all subjects the blood pressure was measured
      subsequently in four positions: Sitting blood pressure was taken from the left
      arm, which was flexed at the elbow and supported at the heart level on the chair.
      After at least one minute of standing, the blood pressure was then taken
      standing, with the arm supported at the elbow and the cuff at the heart level.
      After one minute of rest, the blood pressure was subsequently taken supine
      position. Finally, after one minute the blood pressure was again taken in this
      last position with supine position with crossed legs. RESULTS: The blood pressure
      tended to drop in the standing position compared with the sitting, supine and
      supine with crossed legs. Systolic and diastolic blood pressure was the highest
      in supine position when compared the other positions. There was a difference
      between systolic blood pressures and this was statistically significant (P <
      0.001) but the difference between diastolic blood pressure was not statistically
      significant (P > 0.05). All changes in systolic blood pressure were statistically
      significant except those from supine to supine position with crossed legs.
      RELEVANCE TO CLINICAL PRACTICE: When assessing blood pressure it is important to
      take the position of the patient into consideration. Also, blood pressure
      measurement must be taken in sitting position with the arms supported at the
      right a trial level.

PMID- 17181674
TI  - A systematic review of topical skin care in aged care facilities.
AB  - AIM: This systematic review aimed to evaluate the best available evidence
      regarding the effectiveness of topical skin care interventions for residents of
      aged care facilities. INTRODUCTION: Natural changes to skin, as well as increased
      predisposition to pressure sores and incontinence, means residents of aged care
      facilities readily require topical skin care. A range of interventions exist that
      aim to maintain or improve the integrity of skin of older adults. METHODS:
      Pubmed, Embase, Current Contents, CINAHL and The Cochrane Library databases were
      searched, as well as Health Technology Assessment websites up to April 2003.
      Systematic reviews and randomized or non-randomized controlled trials were
      evaluated for quality and data were independently extracted by two reviewers.
      RESULTS: The effectiveness of topical skin interventions was variable and
      dependent on the skin condition being treated. Studies examined the effectiveness
      of washing products on incontinence irritated skin. Disposable bodyworns may
      prevent deterioration of skin condition better than non-disposable underpads or
      bodyworns. Clinisan, a no-rinse cleanser may reduce the incidence of incontinence
      associated pressure ulcers when compared with soap and water. CONCLUSION: In
      general the quality of evidence for interventions to improve or maintain the skin
      condition in the older person was poor and more research in this area is needed.
      RELEVANCE TO CLINICAL PRACTICE: Skin care is a major issue for nurses working
      with older people. On the basis of this review no clear recommendations can be
      made. This lack of strong evidence for nurses to base effective practice
      decisions is problematic. However, the 'best' evidence suggests that disposable
      bodyworns are a good investment in the fight against skin deterioration. No rinse
      cleansers are to be preferred over soap and the use of the bag bath appears to be
      a useful practice to reduce the risk of dry skin (a risk factor for breaches in
      skin integrity).

PMID- 17181676
TI  - Adherence to drug treatment in association with how the patient perceives care
      and information on drugs.
AB  - AIM: This study was to explore concordance with drugs prescribed and the
      patient's self-reported drug consumption, in relation to the older patient's
      perceived care and information given. BACKGROUND: Lack of adherence to
      prescriptions may lead to therapeutic failure with risks for relapse, unnecessary
      suffering and increased costs. DESIGN: A cross-sectional study with structured
      interviews of 200 patients who had recently been treated in a medical ward.
      METHODS: Patients' medical records were studied to obtain information on their
      current use of drugs. The data were analyzed by logistic regression, adherence
      being the dependent response variable. RESULTS: The mean age of the study group
      was 79 years. The number of drugs reported in the medical chart ranged from one
      to 17 with a mean of 6.9. The patients reported a drug consumption ranging from 0
      to 24 with a mean of 7.3. When comparing the interview results with the
      information in the medical charts, 30% of the patients showed adherence. An
      association was found between adherence and self-reported health status. Patients
      in the non-adherent group reported a higher consumption of drugs. Patients felt
      that the opportunity to ask questions of either the responsible physicians or of
      the nurses was influential in decreasing risk. CONCLUSION: In this study, the
      patient's total drug consumption was considered. The study showed a large
      discrepancy between the drugs stated in the medical chart and patient's self
      reported drug consumption. The study failed to show that perceived information or
      educational level had an impact on the results but implicate that the quality of
      information influences adherence. RELEVANCE TO CLINICAL PRACTICE: It is of
      importance to recognize patients at risk for non-adherence. Decreased health
      status and many drugs are the main risk factors for patients being non-adherent,
      and should be recognized as such.

PMID- 17181677
TI  - A first-line nurse manager's goal-profile.
AB  - AIM: The aim of this case study was to acquire understanding concerning the first
      line nurse manager's goal-profile, i.e. prioritization of goals in her work as a
      first-line nurse manager, through use of an action-theoretic and confirmatory
      theory. BACKGROUND: The first-line nurse manager's pivotal role regarding quality
      of care and development in relation to on-going changes in the health care sector
      is stressed by many researchers and the transition from nurse to manager is
      described as a demanding challenge for the first-line nurse manager. METHODS: The
      case study described in this paper concerns a first-line nurse manager in an
      actual working environment in care of older people. Data collection comprised
      interviews, observations, a job description and policy documents. A hermeneutic
      interpretation was used for data analysis. RESULTS: The results showed that the
      first-line nurse manager had three goals in her goal-profile, in the following
      order of priority: (i) a nurse goal that she had strongly accepted and in which
      she had excellent control, (ii) an administrator goal that she had accepted and
      in which she had control, (iii) a leadership goal that she had not accepted and
      in which she did not have control. Both the administrator and leadership goals
      were based on her job description, but the nurse goal was a personally chosen
      goal based on her own self-relation/goal-fulfillment. CONCLUSION: The first-line
      nurse manager's prioritized self-identity, based on successful realization of
      goals in her goal-profile, was decisive in the manifestation of her work.
      RELEVANCE TO CLINICAL PRACTICE: This study contributes to a new understanding of
      the first-line nurse manager's self-identity related to work in terms of goal
      acceptance and goal control of prioritized goals. This action-theoretic approach
      could be a valuable 'key' for understanding leadership (or lack of leadership) in
      clinical practice.

PMID- 17181678
TI  - Vaginal birth after caesarean section (VBAC): exploring women's perceptions.
AB  - AIMS AND OBJECTIVES: This study was designed to complement local audit data by
      examining the lived experience of women who elected to attempt a vaginal birth
      following a previous caesarean delivery. The study sought to determine whether or
      not women were able to exercise informed choice and to explore how they made
      decisions about the method of delivery and how they interpreted their experiences
      following the birth. BACKGROUND: The rising operative birth rate in the UK
      concerns both obstetricians and midwives. Although the popular press has
      characterized birth by caesarean section as the socialites' choice, in reality,
      maternal choice is only one factor in determining the method of birth. However,
      in considering the next delivery following a caesarean section, maternal choice
      may be a significant indicator. While accepted current UK practice favours
      vaginal birth after caesarean (VBAC) in line with the research evidence
      indicating reduced maternal morbidity, lower costs and satisfactory neonatal
      outcomes, Lavender et al. point out that partnership in choice has emerged as a
      key factor in the decision-making process over the past few decades. Chaung and
      Jenders explored the issue of choice in an earlier study and concluded that the
      best method of subsequent delivery, following a caesarean birth, is dependent on
      a woman's preference. DESIGN AND METHODOLOGY: Using a phenomenological approach
      enabled a holistic exploration of women's lived experiences of vaginal birth
      after the caesarean section. RESULTS: This was a qualitative study and, as such,
      the findings are not transferable to women in general. However, the results
      confirmed the importance of informed choice and raised some interesting issues
      meriting the further exploration. CONCLUSIONS: Informed choice is the key to
      effective women-centred care. Women must have access to non-biased evidence-based
      information in order to engage in a collaborative partnership of equals with
      midwives and obstetricians. RELEVANCE TO CLINICAL PRACTICE: This study is
      relevant to clinical practice as it highlights the importance of informed choice
      and reminds practitioners that, for women, psycho-social implications may
      supersede their physical concerns about birth.

PMID- 17181679
TI  - Management of gestational diabetes from the patient's perspective--a comparison
      of Swedish and Middle-Eastern born women.
AB  - AIM: To explore patients' evaluation of a specialized diabetes clinic for
      management of women with gestational diabetes born in Sweden and the Middle East
      and its contribution to a decreased level of stress and improved coping
      capability to promote health in patients receiving care. BACKGROUND: No studies
      comparing patients' perceptions of healthcare in women of different origin with
      gestational diabetes have been found. A perceived clinical problem in specialized
      diabetes care is of lower activity level in self-care in foreign- than Swedish
      born women and the question is whether the healthcare organization is optimal in
      meeting different individuals' needs. DESIGN: Explorative study. METHOD: Semi
      structured individual interviews by external evaluators. PARTICIPANTS:
      Consecutive sample. Females with gestational diabetes, 13 born in Sweden and 14
      born in the Middle East. RESULTS: The healthcare model was perceived as
      functioning well. Swedish women were problem focused and information seeking.
      Frustration and stress were increased due to perceived delay in information
      concerning gestational diabetes, limited access to telephone service and lack of
      confidence in staff because they lacked the expected competence. Control of
      gestational diabetes and pregnancy by different persons led to perceived lack of
      holistic care. Women from the Middle East felt cared, had been given the
      necessary information and claimed to follow advice. Adequate information reduced
      respondents' anxiety and increased their control over the situation. CONCLUSIONS:
      The clinic needs to be further improved by adapting programmes to persons to
      become problem focused by giving adequate information immediately. RELEVANCE TO
      CLINICAL PRACTICE: Cultural differences in coping strategies and attitudes to
      gestational diabetes need to be considered. Training of staff working with
      gestational diabetes patients is urgently needed.

PMID- 17181680
TI  - Primiparas with or without oxytocin augmentation: a prospective descriptive
      study.
AB  - AIMS: The aim of this study was to determine during which phase of delivery
      augmentation is started when used and to establish any correlation that might
      exist between the oxytocin infusion and the evaluations by primiparas themselves
      of their labour pain, strength of contractions and fatigue. In addition, we
      wanted to determine any differences in duration between labour with and labour
      without augmentation. We finally wanted to measure the incidence of instrumental
      deliveries, perineal trauma and neonatal outcome among the augmented vs. the non
      augmented groups. BACKGROUND: The most commonly diagnosed complication in
      primiparas is ineffective contractions or protracted labour, otherwise known as
      dystocia, which literally means arrested or prolonged labour. Different
      treatments have been tried during the active phase of labour as well as the
      second stage of labour. The most common treatment today is amniotomy, often used
      in combination with an intravenous oxytocin infusion. MATERIALS AND METHODS: The
      study was conducted at the hospital in Ostersund in central Sweden from August
      1998 to September 1999. Consecutive primiparas giving birth at full-term were
      selected to the study. The inclusion criteria were an uncomplicated pregnancy and
      a spontaneous single delivery with head presentation. The total number of
      participants was 164. RESULTS: The results showed that 50 of 164 primiparas
      needed no augmentation, while 88 were augmented during the active phase and 26
      during the second stage of labour. The duration of the active phase [median (md)
      4 hours 45 minutes, 6 hours 49 minutes and 6 hours 20 minutes respectively for
      the different groups, P = 0.03], the time between full dilation of the cervix and
      the start of the second stage (md 20 minutes, 30 minutes and 60 minutes
      respectively, P = 0.012) and the duration of the second stage of labour (md 40
      minutes, 44 minutes and 60 minutes respectively, P = 0.04) were significantly
      longer in the augmented groups. Operative deliveries, too, were more frequent in
      the augmented groups. There was a significantly higher rate of perineotomies in
      the group augmented during the second stage of labour. There were, however, no
      differences in Apgar score <7 at 1 minute. pH in the umbilical cord and the base
      deficit were higher in the group which were augmented during the second stage of
      labour (P = 0.02 and P = 0.06 respectively). Women describing their impression of
      the experience as a whole generally gave it a high rating, but women who were
      augmented during the second stage of labour gave the experience a significantly
      lower score (P = 0.01). CONCLUSION: Augmentation is used in unusually prolonged
      deliveries. We did not find that augmentation involved a higher frequency of
      perineal trauma, although it was correlated with a higher frequency of operative
      deliveries. There was no correlation between the oxytocin infusion and the
      primiparas' descriptions of the strength of contractions, pain and fatigue,
      although greater use of epidurals was observed in women with augmented labour.
      The number of nulliparas in this study was too small to analyse the incidence of
      ruptures in the sphincter or draw conclusions about differences between the
      groups with regard to Apgar scores or metabolic acidosis. RELEVANCE TO CLINICAL
      PRACTICE: In clinical practice, good routines concerning oxytocin augmentation
      are crucial. Interventions as oxytocin augmentation seem to cause harm to mother
      and child. To evaluate interventions continuously in obstetric care is therefore
      important.

PMID- 17181681
TI  - An analysis of the stressors and coping strategies of Chinese adults with a
      partner admitted to an intensive care unit in Hong Kong: an exploratory study.
AB  - AIMS: The aim of this study was to identify the major stressors affecting Chinese
      adults whose partner had been admitted to an intensive care unit and to
      understand the major coping strategies employed to manage such stressors.
      BACKGROUND: Recently a greater number of patients of higher acuity have been
      admitted to intensive care units and survive lengthy illnesses of an
      unpredictable course. Such critical illnesses have been identified as a major
      life event to family members of these patients. Little is known, however, about
      the stressors and coping mechanisms of Chinese adults whose critically ill
      partner is admitted to an intensive care unit. METHODS: An exploratory
      qualitative design was selected to achieve the aims of the study. A purposive
      sample of 10 Chinese adults with a partner in an intensive care unit of a
      regional general hospital in Hong Kong participated in tape-recorded semi
      structured interviews. Content analysis was employed to analyse the translated
      interviews. FINDINGS: Categories of stressors included uncertainty, difficulties
      in communication, changes in roles and responsibilities, difficulties in decision
      making, financial strain as well as changes in relationships. Analysis identified
      a range of coping strategies which included seeking information, seeking support,
      reliance on cultural beliefs and practices, turning to religious beliefs,
      maintaining hope and acceptance of illness. CONCLUSIONS: The findings demonstrate
      the importance of cultural beliefs and practices in determining the coping
      mechanisms employed to manage the stressors identified by this sample of Chinese
      adults. Such findings indicate the use of both internal and external coping
      strategies in order to maintain equilibrium in the family. RELEVANCE TO CLINICAL
      PRACTICE: Implications for nursing practice highlight the significance of seeking
      information throughout the critical period and also culturally appropriate
      support from healthcare professionals.

PMID- 17181682
TI  - Co-ordination of the discharge planning process in critical care.
AB  - AIM AND OBJECTIVES: This article reports on the current discharge planning
      beliefs in relation to the co-ordination of the discharge planning process in the
      critical care environment in the health care system in the state of Victoria,
      Australia. As there is a paucity of previous studies examining discharge planning
      in critical care nursing knowledge about the phenomena is consequently limited.
      BACKGROUND: The study reported here is part of a larger study exploring critical
      care nurses' perceptions and understanding of the discharge planning process in
      the health care system in the state of Victoria, Australia. While a number of
      different discharge planning models are reported in the literature there is no
      agreement on the most effective or the most efficient model. DESIGN: An
      exploratory descriptive research design was used for this study. METHODS: A total
      of 502 Victorian critical care nurses were approached to take part in the study.
      A total of 218 participants completed the survey, which represented a nett
      response rate of 43.4%. The data from the questionnaire were entered into the
      Statistical Package for Social Sciences (SPSS) Base 10.0. This allowed
      calculation of descriptive statistics and statistical analysis using chi-square
      test for goodness-of-fit. RESULTS: While just over half the participants reported
      that the discharge planning process in their unit was co-ordinated by a
      combination of personnel that included a nurse, just under half the participants
      believed that this was an appropriate model. Another key finding was of those
      participants who worked in critical care units using primary nursing, just over
      half responded that the bedside nurse/primary nurse co-ordinated the discharge
      planning process while just under half responded that a combination of health
      care team members, including a nurse, co-ordinated the process. Overall there was
      little support for the designated discharge planning nurse to co-ordinate the
      process. CONCLUSIONS: The findings presented here suggest critical care nurses
      need to examine who has the ultimate responsibility of co-ordinating the critical
      care patient's discharge plan irrespective of the nursing model employed within
      the critical care ward. There is the need to ensure that when discharge planning
      becomes everybody's responsibility it ultimately does not become no-one's
      responsibility. RELEVANCE TO CLINICAL PRACTICE: If discharge planning practices
      are to be changed with the introduction of new discharge planning models in the
      critical care environment then it is important not only to know current practice
      but also the perceptions of critical care nurses in terms of who they believe
      should co-ordinate the discharge planning process.

PMID- 17181683
TI  - Being an intensive care nurse related to questions of withholding or withdrawing
      curative treatment.
AB  - AIMS AND OBJECTIVES: The aim of the study was to acquire a deeper understanding
      of what it is to be an intensive care nurse in situations related to questions of
      withholding or withdrawing curative treatment. BACKGROUND: Nurses in intensive
      care units regularly face critically ill patients. Some patients do not benefit
      from the treatment and die after days or months of apparent pain and suffering. A
      general trend is that withdrawal of treatment in intensive care units is
      increasing. Physicians are responsible for decisions concerning medical
      treatment, but as nurses must carry out physicians' decisions, they are involved
      in the consequences. DESIGN AND METHODS: The research design was qualitative,
      based on interpretative phenomenology. The study was carried out at an adult
      intensive care unit in Norway. Data were collected by group interviews inspired
      by focus group methodology. Fourteen female intensive care nurses participated,
      divided into two groups. Colaizzi's model was used in the process of analysis.
      RESULTS: The analysis revealed four main themes which captured the nurses'
      experiences: loneliness in responsibility, alternation between optimism and
      pessimism, uncertainty--a constant shadow and professional pride despite little
      formal influence. The essence of being an intensive care nurse in the care of
      patients when questions were raised concerning curative treatment or not, was
      understood as 'being a critical interpreter and a dedicated helper.' CONCLUSIONS:
      The findings underpin the important role of intensive care nurses in providing
      care and treatment to patients related to questions of withholding or withdrawing
      curative treatment. RELEVANCE TO CLINICAL PRACTICE: The findings also show the
      need for physicians, managers and intensive care nurses themselves to recognize
      the burdens intensive care nurses carry and to appreciate their knowledge as an
      important contribution in decision making.

PMID- 17181684
TI  - The effect of ambulation after cardiac catheterization on patient outcomes.

PMID- 17181685
TI  - Commentary on Jerlock M, Gaston-Johansson F & Danielson E (2005) Living with
      unexplained chest pain. Journal of Clinical Nursing 14, 956-964.

PMID- 17181687
TI  - Commentary on Farnell S, Maxwell L, Tan, S, Rhodes A & Phillips A (2005)
      Temperature measurement: comparison of non-invasive methods used in adult
      critical care. Journal of Clinical Nursing 14, 632-639.

PMID- 17181692
TI  - Probabilistic epigenesis.
AB  - The notion that phenotypic traits, including behavior, can be predetermined has
      slowly given way in biology and psychology over the last two decades. This shift
      in thinking is due in large part to the growing evidence for the fundamental role
      of developmental processes in the generation of the stability and variations in
      phenotype that researchers in developmental and evolutionary sciences seek to
      understand. Here I review the tenets of a metatheoretical model of development
      called probabilistic epigenesis (PE) and explore its implications for furthering
      our understanding of developmental and evolutionary processes. The PE framework
      emphasizes the reciprocity of influences within and between levels of an
      organism's developmental manifold (genetic activity, neural activity, behavior,
      and the physical, social, and cultural influences of the external environment)
      and the ubiquity of gene-environment interaction in the realization of all
      phenotypes.

PMID- 17181693
TI  - Gene-environment interdependence.
AB  - Behavioural genetics was initially concerned with partitioning population
      variance into that due to genetics and that due to environmental influences. The
      implication was that the two were separate and it was assumed that gene
      environment interactions were usually of so little importance that they could
      safely be ignored. Theoretical considerations suggested that that was unlikely to
      be true and empirical findings are now accumulating on the demonstrated and
      replicated biological interactions between identified common single genetic
      variants and the operation of environmentally mediated risks. The paper outlines
      the evidence and considers why it is changing concepts in ways that matter.

PMID- 17181694
TI  - Microarrays.
AB  - Microarrays are revolutionizing genetics by making it possible to genotype
      hundreds of thousands of DNA markers and to assess the expression (RNA
      transcripts) of all of the genes in the genome. Microarrays are slides the size
      of a postage stamp that contain millions of DNA sequences to which single
      stranded DNA or RNA can hybridize. This miniaturization requires little DNA or
      RNA and makes the method fast and inexpensive; multiple assays of each target
      make the method highly accurate. DNA microarrays with hundreds of thousands of
      DNA markers have made it possible to conduct systematic scans of the entire
      genome to identify genetic associations with complex disorders or dimensions
      likely to be influenced by many genes of small effect size. RNA microarrays can
      provide snapshots of gene expression across all of the genes in the genome at any
      time in any tissue, which has far-reaching applications such as structural and
      functional 'genetic neuroimaging' and providing a biological basis for
      understanding environmental influence.

PMID- 17181695
TI  - Attention genes.
AB  - A major problem for developmental science is understanding how the cognitive and
      emotional networks important in carrying out mental processes can be related to
      individual differences. The last five years have seen major advances in
      establishing links between alleles of specific genes and the neural networks
      underlying aspects of attention. These findings have the potential of
      illuminating important aspects of normal development and its pathologies. We need
      to learn how genes and experience combine to influence the structure of neural
      networks and the efficiency with which they are exercised. Methods for addressing
      these issues are central to progress in the decade ahead.

PMID- 17181697
TI  - Music, evolution and language.
AB  - Darwin (1871) noted that the human musical faculty 'must be ranked amongst the
      most mysterious with which he is endowed'. Indeed, previous research with human
      infants and young children has revealed that we are born with variable musical
      capabilities. Here, the adaptive purpose served by these differing capabilities
      is discussed with reference to comparative findings regarding the acoustic
      behavior of nonhuman primates. The findings provide evidence supporting Darwin's
      hypothesis of an intermediate stage of human evolutionary history characterized
      by a communication system that resembles music more closely than language and
      possibly acting as a precursor for both current language and music.

PMID- 17181696
TI  - Endless minds most beautiful.
AB  - The marriage of evolution and development to produce the new discipline 'evo
      devo' in biology is situated in the general history of evolutionary biology, and
      its significance for developmental cognitive science is discussed. The discovery
      and description of the highly conserved, robust and 'evolvable' mechanisms that
      organize the vertebrate body plan and fundamental physiology have direct
      implications for what we should investigate in the evolution of behavior and
      cognition.

PMID- 17181698
TI  - Sleeper effects.
AB  - Early experience preserves and refines many capabilities that emerge prenatally.
      Here we describe another role that it plays -- establishing the neural substrate
      for capabilities that emerge at a much later point in development. The evidence
      comes from sleeper effects: permanent deficits when early experience was absent
      in capabilities that normally emerge long after birth. We provide evidence of
      sleeper effects for three aspects of vision, based on our research with children
      who were deprived of early visual input by congenital cataracts: contrast
      sensitivity for mid and high spatial frequencies, holistic face processing, and
      the ability to recognize the identity of faces based on small differences in the
      spacing among facial features.

PMID- 17181699
TI  - What's in a look?
AB  - The most common behavioral technique used to study infant perception, cognition,
      language, and social development is some variant of looking time. Since its
      inception as a reliable method in the late 1950s, a tremendous increase in
      knowledge about infant competencies has been gained by inferences made from
      measures of looking time. Here we examine the logic, utility, and future
      prospects for further gains in our understanding of infant cognition from the use
      of looking time measures.

PMID- 17181700
TI  - Action in development.
AB  - It is argued that cognitive development has to be understood in the functional
      perspective provided by actions. Actions reflect all aspects of cognitive
      development including the motives of the child, the problems to be solved, and
      the constraints and possibilities of the child's body and sensorimotor system.
      Actions are directed into the future and their control is based on knowledge of
      what is going to happen next. Such knowledge is available because events are
      governed by rules and regularities. The planning of actions also requires
      knowledge of the affordances of objects and events. An important aspect of
      cognitive development is about how the child acquires such knowledge.

PMID- 17181702
TI  - Dynamic instabilities as mechanisms for emergence.
AB  - That competences may emerge given appropriate environmental and behavioral
      context is a long-standing theme in developmental research. Work in the motor
      domain, but also in cognitive development, has made it possible to transform this
      idea into a mechanistic account closely linked to empirical evidence. In dynamic
      systems thinking, such capacities as keeping a motor goal in mind, remembering a
      location, or resisting a motor habit, are all understood in terms of the
      generation of stable patterns of neuronal activation. These may be input-driven,
      but also be stabilized by interactions within neuronal representations. A key
      theoretical insight is that whether a particular pattern of activation is stable
      or not is not determined by any single factor, learning process, or structural
      parameter. Instead, ongoing activity, recent activation history, current input,
      all may affect when a particular dynamic regime is reachable. In spite of such
      broad interdependence, sharp transitions may characterize the onset of a skill in
      any given context. Dynamic instabilities are the mechanistic basis for this
      phenomenon and thus form the basis for understanding development in terms of
      emergence. We exemplify the concepts of instability and emergence around the
      phenomenon of infant perseverative reaching and discuss implications for
      identifying key markers of development and their link to neuronal processes.

PMID- 17181701
TI  - The dynamic lift of developmental process.
AB  - What are the essential properties of human intelligence, currently unparalleled
      in its power relative to other biological forms and relative to artificial forms
      of intelligence? We suggest that answering this question depends critically on
      understanding developmental process. This paper considers three principles
      potentially essential to building human-like intelligence: the heterogeneity of
      the component processes, the embedding of development in a social world, and
      developmental processes that change the cognitive system as a function of the
      history of soft-assemblies of these heterogeneous processes in specific tasks.
      The paper uses examples from human development and from developmental robotics to
      show how these processes also may underlie biological intelligence and enable us
      to generate more advanced forms of artificial intelligence.

PMID- 17181703
TI  - Neuroconstructivism.
AB  - Neuroconstructivism is a theoretical framework focusing on the construction of
      representations in the developing brain. Cognitive development is explained as
      emerging from the experience-dependent development of neural structures
      supporting mental representations. Neural development occurs in the context of
      multiple interacting constraints acting on different levels, from the individual
      cell to the external environment of the developing child. Cognitive development
      can thus be understood as a trajectory originating from the constraints on the
      underlying neural structures. This perspective offers an integrated view of
      normal and abnormal development as well as of development and adult processing,
      and it stands apart from traditional cognitive approaches in taking seriously the
      constraints on cognition inherent to the substrate that delivers it.

PMID- 17181704
TI  - Atypical epigenesis.
AB  - It is becoming increasingly clear that little in development is predetermined or
      permanently fixed. Rather, gene expression is activity dependent, and epigenesis
      is probabilistic. So, the study of genetic disorders needs to change from the
      still widely held view that developmental disorders can be accounted for in terms
      of intact versus impaired modules, to one which takes serious account of the fact
      that the infant cortex passes from an initial state of high regional
      interconnectivity to a subsequent state of increasing specialization and
      localization of function. With such early interconnectivity in mind,
      developmental neuroscientists must consider the possibility that an early deficit
      in one part of the brain may have subtle effects on other parts of the developing
      brain, even when scores fall 'in the normal range'. In studying developmental
      disorders, it is thus crucial to examine not only domains of clear-cut deficit,
      but also domains of behavioural proficiency. Atypical epigenesis may often
      involve a lack of specialization and localization of brain function over
      developmental time, even in cases of behavioural proficiency.

PMID- 17181705
TI  - Core knowledge.
AB  - Human cognition is founded, in part, on four systems for representing objects,
      actions, number, and space. It may be based, as well, on a fifth system for
      representing social partners. Each system has deep roots in human phylogeny and
      ontogeny, and it guides and shapes the mental lives of adults. Converging
      research on human infants, non-human primates, children and adults in diverse
      cultures can aid both understanding of these systems and attempts to overcome
      their limits.

PMID- 17181706
TI  - Comparative cognitive development.
AB  - This paper aims to compare cognitive development in humans and chimpanzees to
      illuminate the evolutionary origins of human cognition. Comparison of
      morphological data and life history strongly highlights the common features of
      all primate species, including humans. The human mother-infant relationship is
      characterized by the physical separation of mother and infant, and the stable
      supine posture of infants, that enables vocal exchange, face-to-face
      communication, and manual gestures. The cognitive development of chimpanzees was
      studied using the participation observation method. It revealed that humans and
      chimpanzees show similar development until 3 months of age. However, chimpanzees
      have a unique type of social learning that lacks the social reference observed in
      human children. Moreover, chimpanzees have unique immediate short-term memory
      capabilities. Taken together, this paper presents a plausible evolutionary
      scenario for the uniquely human characteristics of cognition.

PMID- 17181707
TI  - Cognitive variability.
AB  - Children's thinking is highly variable at every level of analysis, from neural
      and associative levels to the level of strategies, theories, and other aspects of
      high-level cognition. This variability exists within people as well as between
      them; individual children often rely on different strategies or representations
      on closely related problems presented close in time. Recognizing such variability
      can help us both describe development more accurately and better explain how
      cognitive change occurs.

PMID- 17181708
TI  - Is speech learning 'gated' by the social brain?
AB  - I advance the hypothesis that the earliest phases of language acquisition -- the
      developmental transition from an initial universal state of language processing
      to one that is language-specific -- requires social interaction. Relating human
      language learning to a broader set of neurobiological cases of communicative
      development, I argue that the social brain 'gates' the computational mechanisms
      involved in human language learning.

PMID- 17181709
TI  - Shared intentionality.
AB  - We argue for the importance of processes of shared intentionality in children's
      early cognitive development. We look briefly at four important social-cognitive
      skills and how they are transformed by shared intentionality. In each case, we
      look first at a kind of individualistic version of the skill -- as exemplified
      most clearly in the behavior of chimpanzees -- and then at a version based on
      shared intentionality -- as exemplified most clearly in the behavior of human 1-
      and 2-year-olds. We thus see the following transformations: gaze following into
      joint attention, social manipulation into cooperative communication, group
      activity into collaboration, and social learning into instructed learning. We
      conclude by highlighting the role that shared intentionality may play in
      integrating more biologically based and more culturally based theories of human
      development.

PMID- 17181711
TI  - Trust.
AB  - Children rely extensively on others' testimony to learn about the world. However,
      they are not uniformly credulous toward other people. From an early age,
      children's reliance on testimony is tempered by selective trust in particular
      informants. Three- and 4-year-olds monitor the accuracy or knowledge of
      informants, including those that are familiar. They prefer to seek and endorse
      information provided by someone who has proved accurate in the past rather than
      someone who has made mistakes or acknowledged ignorance. Future research is
      likely to pinpoint other heuristics that children use to filter incoming
      testimony and may reveal more generalized patterns of trust and mistrust among
      individual children.

PMID- 17181710
TI  - 'Like me': a foundation for social cognition.
AB  - Infants represent the acts of others and their own acts in commensurate terms.
      They can recognize cross-modal equivalences between acts they see others perform
      and their own felt bodily movements. This recognition of self-other equivalences
      in action gives rise to interpreting others as having similar psychological
      states such as perceptions and emotions. The 'like me' nature of others is the
      starting point for social cognition, not its culmination.

PMID- 17181712
TI  - On pedagogy.
AB  - Humans are adapted to spontaneously transfer relevant cultural knowledge to
      conspecifics and to fast-learn the contents of such teaching through a human
      specific social learning system called 'pedagogy' (Csibra & Gergely, 2006).
      Pedagogical knowledge transfer is triggered by specific communicative cues (such
      as eye-contact, contingent reactivity, the prosodic pattern of 'motherese', and
      being addressed by one's own name). Infants show special sensitivity to such
      'ostensive' cues that signal the teacher's communicative intention to manifest
      new and relevant knowledge about a referent object. Pedagogy offers a novel
      functional perspective to interpret a variety of early emerging triadic
      communicative interactions between adults and infants about novel objects they
      are jointly attending to. The currently dominant interpretation of such triadic
      communications (mindreading) holds that infants interpret others' object-directed
      manifestations in terms of subjective mental states (such as emotions,
      dispositions, or intentions) that they attribute to the other person's mind. We
      contrast the pedagogical versus the mindreading account in a new study testing 14
      month-olds' interpretation of others' object-directed emotion expressions
      observed in a communicative cueing context. We end by discussing the far-reaching
      implications of the pedagogical perspective for a wide range of early social
      cognitive competences, and for providing new directions for future research on
      child development.

PMID- 17181713
TI  - Religion is natural.
AB  - Despite its considerable intellectual interest and great social relevance,
      religion has been neglected by contemporary developmental psychologists. But in
      the last few years, there has been an emerging body of research exploring
      children's grasp of certain universal religious ideas. Some recent findings
      suggest that two foundational aspects of religious belief - belief in mind-body
      dualism, and belief in divine agents -- come naturally to young children. This
      research is briefly reviewed, and some future directions are discussed.

PMID- 17181716
TI  - John C. Avise--recipient of 2006 Molecular Ecology prize.

PMID- 17181714
TI  - Interrelated and interdependent.
AB  - The possibilities for building and nourishing connections among the social,
      cultural, neuroscientific, biological, and cognitive sciences in the service of
      understanding children and their development are tremendously exciting. Crossing,
      and integrating across, disciplinary boundaries, especially those disciplines
      relating to biology/neuroscience, society/culture, cognition, emotion,
      perception, and motor function has greatly increased over the last decade and
      hopefully will increase exponentially in the future. All of these aspects of
      being human are multiply-interrelated and we need to make far more progress in
      understanding those interrelations.

PMID- 17181717
TI  - Whose turtles are they, anyway?
AB  - The hawksbill turtle (Eretmochelys imbricata), listed since 1996 by the IUCN as
      Critically Endangered and by the Convention on International Trade in Endangered
      Species (CITES) as an Appendix I species, has been the subject of attention and
      controversy during the past 10 years due to the efforts of some nations to re
      open banned international trade. The most recent debate has centred on whether it
      is appropriate for Cuba to harvest hawksbills from shared foraging aggregations
      within her national waters. In this issue of Molecular Ecology, Bowen et al. have
      used molecular genetic data to show that such harvests are likely to have
      deleterious effects on the health of hawksbill populations throughout the
      Caribbean.

PMID- 17181718
TI  - SINEs of progress: Mobile element applications to molecular ecology.
AB  - Mobile elements represent a unique and under-utilized set of tools for molecular
      ecologists. They are essentially homoplasy-free characters with the ability to be
      genotyped in a simple and efficient manner. Interpretation of the data generated
      using mobile elements can be simple compared to other genetic markers. They exist
      in a wide variety of taxa and are useful over a wide selection of temporal ranges
      within those taxa. Furthermore, their mode of evolution instills them with
      another advantage over other types of multilocus genotype data: the ability to
      determine loci applicable to a range of time spans in the history of a taxon. In
      this review, I discuss the application of mobile element markers, especially
      short interspersed elements (SINEs), to phylogenetic and population data, with an
      emphasis on potential applications to molecular ecology.

PMID- 17181719
TI  - Resource-based adaptive divergence in the freshwater fish Telmatherina from Lake
      Matano, Indonesia.
AB  - Adaptive radiations are an important source of biodiversity, but resolving which
      ecological pressures seed these processes in natural systems remains difficult.
      Here the adaptive radiation among Telmatherina, a genus of freshwater fish
      endemic to an ancient lake in central Sulawesi, Indonesia, was examined to
      determine its causal root. We demonstrate that all Telmatherina in this lake can
      be categorized into three lineages each possessing specialized skull shapes and
      pharyngeal jaw bones allowing them to exploit different resources. These data
      demonstrate a natural example of how resource partitioning has likely initiated
      adaptive radiation in a resource limited environment.

PMID- 17181720
TI  - Mixed-stock analysis reveals the migrations of juvenile hawksbill turtles
      (Eretmochelys imbricata) in the Caribbean Sea.
AB  - Hawksbill turtles (Eretmochelys imbricata) migrate between nesting beaches and
      feeding habitats that are often associated with tropical reefs, but it is
      uncertain which nesting colonies supply which feeding habitats. To address this
      gap in hawksbill biology, we compile previously published and new mitochondrial
      DNA (mtDNA) haplotype data for 10 nesting colonies (N = 347) in the western
      Atlantic and compare these profiles to four feeding populations and four
      previously published feeding samples (N = 626). Nesting colonies differ
      significantly in mtDNA haplotype frequencies (Phi(ST) = 0.588, P < 0.001),
      corroborating earlier conclusions of nesting site fidelity and setting the stage
      for mixed-stock analysis. Feeding aggregations show lower but significant
      structure (Phi(ST) = 0.089, P < 0.001), indicating that foraging populations are
      not homogenous across the Caribbean Sea. Bayesian mixed-stock estimates of the
      origins of juveniles in foraging areas show a highly significant, but shallow,
      correlation with nesting population size (r = 0.378, P = 0.004), supporting the
      premise that larger rookeries contribute more juveniles to feeding areas. A
      significant correlation between the estimated contribution and geographical
      distance from nesting areas (r = -0.394, P = 0.003) demonstrates the influence of
      proximity on recruitment to feeding areas. The influence of oceanic currents is
      illustrated by pelagic stage juveniles stranded in Texas, which are assigned
      primarily (93%) to the upstream rookery in Yucatan. One juvenile had a haplotype
      previously identified only in the eastern Atlantic, invoking rare trans-oceanic
      migrations. The mixed-stock analysis demonstrates that harvests in feeding
      habitats will impact nesting colonies throughout the region, with the greatest
      detriment to nearby nesting populations.

PMID- 17181721
TI  - Detecting female precise natal philopatry in green turtles using assignment
      methods.
AB  - It is well established that sea turtles return to natal rookeries to mate and lay
      their eggs, and that individual females are faithful to particular nesting sites
      within the rookery. Less certain is whether females are precisely returning to
      their natal beach. Attempts to demonstrate such precise natal philopatry with
      genetic data have had mixed success. Here we focused on the green turtles of
      three nesting sites in the Ascension Island rookery, separated by 5-15 km. Our
      approach differed from previous work in two key areas. First, we used male
      microsatellite data (five loci) reconstructed from samples collected from their
      offspring (N = 17) in addition to data for samples taken directly from females (N
      = 139). Second, we employed assignment methods in addition to the more
      traditional F-statistics. No significant genetic structure could be demonstrated
      with F(ST). However, when average assignment probabilities of females were
      examined, those for nesting populations in which they were sampled were indeed
      significantly higher than their probabilities for other populations (Mann-Whitney
      U-test: P < 0.001). Further evidence was provided by a significant result for the
      mAI(C) test (P < 0.001), supporting greater natal philopatry for females compared
      with males. The results suggest that female natal site fidelity was not
      sufficient for significant genetic differentiation among the nesting populations
      within the rookery, but detectable with assignment tests.

PMID- 17181722
TI  - High levels of variation despite genetic fragmentation in populations of the
      endangered mountain pygmy-possum, Burramys parvus, in alpine Australia.
AB  - In endangered mammals, levels of genetic variation are often low and this is
      accompanied by genetic divergence among populations. The mountain pygmy-possum
      (Burramys parvus) is an endangered marsupial restricted to the alpine region of
      Victoria and New South Wales, Australia. By scoring variation at eight
      microsatellite loci, we found that B. parvus populations exhibit high levels of
      genetic divergence and fall into three distinct groups from the northern, central
      and southern areas of the distribution of this species, consistent with previous
      assessments of mitochondrial DNA variation. F(ST) values between populations from
      these regions ranged from 0.19 to 0.54. Within the central area, there was
      further genetic fragmentation, and a linear association between genetic and
      geographical distance. This pattern is likely to reflect limited dispersal across
      barriers despite the fact that individual B. parvus can move several kilometres.
      Levels of genetic variation within populations were high with the exception of a
      southern population where there was evidence of inbreeding. From a conservation
      perspective, all three areas where B. parvus are found should be considered as
      separate gene pools; management of populations within these areas needs to take
      into account the low gene flow between populations, as well as threats posed by
      roads, resorts and other developments in the alpine region. The low genetic
      variability and inbreeding in the southern population is of particular concern
      given the high levels of variability in other B. parvus populations.

PMID- 17181723
TI  - High intercontinental migration rates and population admixture in the sapstain
      fungus Ophiostoma ips.
AB  - Ophiostoma ips is a common fungal associate of various conifer-infesting bark
      beetles in their native ranges and has been introduced into non-native pine
      plantations in the Southern Hemisphere. In this study, we used 10 microsatellite
      markers to investigate the population biology of O. ips in native (Cuba, France,
      Morocco and USA) and non-native (Australia, Chile and South Africa) areas to
      characterize host specificity, reproductive behaviour, and the potential origin
      as well as patterns of spread of the fungus and its insect vectors. The markers
      resolved a total of 41 alleles and 75 haplotypes. Higher genetic diversity was
      found in the native populations than in the introduced populations. Based on the
      origin of the insect vectors, the populations of O. ips in Australia would be
      expected to reflect a North American origin, and those in Chile and South Africa
      to reflect a European origin. However, most alleles observed in the native
      European population were also found in the native North American population; only
      the allele frequencies among the populations varied. This admixture made it
      impossible to confirm the origin of the introduced Southern Hemisphere (SH)
      populations of O. ips. There was also no evidence for specificity of the fungus
      to particular bark beetle vectors or hosts. Although O. ips is thought to be
      mainly self-fertilizing, evidence for recombination was found in the four native
      populations surveyed. The higher genetic diversity in the North American than in
      the European population suggests that North America could be the possible source
      region of O. ips.

PMID- 17181724
TI  - Phylogeography of the Ryukyu robin (Erithacus komadori): population subdivision
      in land-bridge islands in relation to the shift in migratory habit.
AB  - We analysed the mitochondrial control region sequences of 150 Ryukyu robins
      (Erithacus komadori) from five migratory and three sedentary populations. E.
      komadori is endemic to the subtropical Asian islands, is well differentiated
      among populations in morphology and migratory behaviour within its narrow habitat
      range, and is ideal for examining the effects of altered migratory habits on
      population differentiation. Maximum-likelihood analysis among the haplotypes
      resulted in the generation of a single tree in which two phylogenetic clades
      corresponding to the two subspecies were evident. Within the northern lineage,
      three distinctive subgroups of populations (one migratory and two sedentary
      groups) were observed by population genetic analysis. The migration-related wing
      morphology and molecular data were then compared among groups. The wing shape of
      the northern lineage was significantly more pointed than that of the southern
      sedentary lineage, and they were exclusively discriminated from each other. The
      difference was not so apparent between the sedentary and migratory groups within
      the northern lineage, suggesting that the present northern subspecies is
      primarily a migratory lineage. The different migratory behaviours of the robin
      played an apparent role in maintaining the genetic structure at two different
      levels--one between the southern and northern lineages and the other between the
      sedentary and migratory groups within the northern lineage. While gene flow had
      long been maintained among the islands occupied by migratory individuals,
      migrants have been unable to contribute to the gene pool of the sedentary
      populations despite passing through the breeding range of such populations twice
      each year.

PMID- 17181725
TI  - Absence of population structure of turbot (Psetta maxima) in the Baltic Sea.
AB  - We found low, albeit significant, genetic differentiation among turbot (Psetta
      maxima) in the Baltic Sea but in contrast to earlier findings we found no
      evidence of isolation by distance. In fact temporal variation among years in one
      locality exceeded spatial variation among localities. This is an unexpected
      result since adult turbot are sedentary and eggs are demersal at the salinities
      occurring in the Baltic. Our findings are most likely explained by the fact that
      we sampled fish that were born after/during a large influx of water to the Baltic
      Sea, which may have had the consequence that previously locally and relatively
      sedentary populations became admixed. These results suggest that populations that
      colonize relatively variable habitats, like the Baltic, face problems. Any
      adaptations to local conditions that may build up during stable periods may
      quickly become eroded when conditions change and/or when populations become
      admixed. Our results indicate that the ability of turbot to survive and reproduce
      at the low salinity in the Baltic is more likely due to phenotypic plasticity
      than a strict genetic adaptation to low salinity.

PMID- 17181726
TI  - The genetic effective and adult census size of an Australian population of tiger
      prawns (Penaeus esculentus).
AB  - This study compares estimates of the census size of the spawning population with
      genetic estimates of effective current and long-term population size for an
      abundant and commercially important marine invertebrate, the brown tiger prawn
      (Penaeus esculentus). Our aim was to focus on the relationship between genetic
      effective and census size that may provide a source of information for viability
      analyses of naturally occurring populations. Samples were taken in 2001, 2002 and
      2003 from a population on the east coast of Australia and temporal allelic
      variation was measured at eight polymorphic microsatellite loci. Moments-based
      and maximum-likelihood estimates of current genetic effective population size
      ranged from 797 to 1304. The mean long-term genetic effective population size was
      9968. Although small for a large population, the effective population size
      estimates were above the threshold where genetic diversity is lost at neutral
      alleles through drift or inbreeding. Simulation studies correctly predicted that
      under these experimental conditions the genetic estimates would have non-infinite
      upper confidence limits and revealed they might be overestimates of the true
      size. We also show that estimates of mortality and variance in family size may be
      derived from data on average fecundity, current genetic effective and census
      spawning population size, assuming effective population size is equivalent to the
      number of breeders. This work confirms that it is feasible to obtain accurate
      estimates of current genetic effective population size for abundant Type III
      species using existing genetic marker technology.

PMID- 17181729
TI  - Phylogeography of the green turtle, Chelonia mydas, in the Southwest Indian
      Ocean.
AB  - Patterns of mitochondrial DNA (mtDNA) variation were used to analyse the
      population genetic structure of southwestern Indian Ocean green turtle (Chelonia
      mydas) populations. Analysis of sequence variation over 396 bp of the mtDNA
      control region revealed seven haplotypes among 288 individuals from 10 nesting
      sites in the Southwest Indian Ocean. This is the first time that Atlantic Ocean
      haplotypes have been recorded among any Indo-Pacific nesting populations.
      Previous studies indicated that the Cape of Good Hope was a major biogeographical
      barrier between the Atlantic and Indian Oceans because evidence for gene flow in
      the last 1.5 million years has yet to emerge. This study, by sampling localities
      adjacent to this barrier, demonstrates that recent gene flow has occurred from
      the Atlantic Ocean into the Indian Ocean via the Cape of Good Hope. We also found
      compelling genetic evidence that green turtles nesting at the rookeries of the
      South Mozambique Channel (SMC) and those nesting in the North Mozambique Channel
      (NMC) belong to separate genetic stocks. Furthermore, the SMC could be subdivided
      in two different genetic stocks, one in Europa and the other one in Juan de Nova.
      We suggest that this particular genetic pattern along the Mozambique Channel is
      attributable to a recent colonization from the Atlantic Ocean and is maintained
      by oceanic conditions in the northern and southern Mozambique Channel that
      influence early stages in the green turtle life cycle.

PMID- 17181728
TI  - Speciation and rapid phenotypic differentiation in the yellow-rumped warbler
      Dendroica coronata complex.
AB  - The relative importance of the Pleistocene glacial cycles in driving avian
      speciation remains controversial, partly because species limits in many groups
      remain poorly understood, and because current taxonomic designations are often
      based on phenotypic characteristics of uncertain phylogenetic significance. We
      use mtDNA sequence data to examine patterns of genetic variation, sequence
      divergence and phylogenetic relationships between phenotypically distinct groups
      of the yellow-rumped warbler complex. Currently classified as a single species,
      the complex is composed of two North American migratory forms (myrtle warbler
      Dendroica coronata coronata and Audubon's warbler Dendroica coronata auduboni),
      and two largely sedentary forms: Dendroica coronata nigrifrons of Mexico, and
      Dendroica coronata goldmani of Guatemala. The latter are typically considered to
      be races of the Audubon's warbler based on plumage characteristics. However,
      mtDNA sequence data reveal that sedentary Mesoamerican forms are reciprocally
      monophyletic to each other and to migratory forms, from which they show a long
      history of isolation. In contrast, migratory myrtle and Audubon's warblers form a
      single cluster due to high levels of shared ancestral polymorphism as evidenced
      by widespread sharing of mtDNA haplotypes despite marked phenotypic
      differentiation. Sedentary and migratory forms diverged in the early Pleistocene,
      whereas phenotypic differentiation between the two migratory forms has occurred
      in the Holocene and is likely the result of geographical isolation and subsequent
      range expansion since the last glaciation. Our results underscore the importance
      of Quaternary climatic events in driving songbird speciation and indicate that
      plumage traits can evolve remarkably fast, thus rendering them potentially
      misleading for inferring systematic relationships.

PMID- 17181727
TI  - Genetic connectivity in the Florida reef system: comparative phylogeography of
      commensal invertebrates with contrasting reproductive strategies.
AB  - Effective spatial management of coral reefs including design of marine protected
      areas requires an understanding of interpopulation genetic connectivity. We
      assessed gene flow along 355 km of the Florida reef system and between Florida
      and Belize in three commensal invertebrates occupying the same host sponge
      (Callyspongia vaginalis) but displaying contrasting reproductive dispersal
      strategies: the broadcast-spawning brittle star Ophiothrix lineata and two
      brooding amphipods Leucothoe kensleyi and Leucothoe ashleyae. Multiple analytical
      approaches to sequence variation in the mitochondrial COI gene demonstrated a
      high degree of overall connectivity for all three species along the Florida reef
      system. Ophiothrix lineata showed significant genetic structuring between Florida
      and Belize, and a pattern of isolation by distance but no significant genetic
      structuring along the Florida coastline. Bayesian estimates of migration detected
      a strong southerly dispersal bias for O. lineata along the Florida reef system,
      contrary to the general assumption of northerly gene flow in this region based on
      the direction of the Florida Current. Both amphipods, despite direct development,
      also showed high gene flow along the Florida reef system. Multiple inferences of
      long-distance dispersal from a nested clade analysis support the hypothesis that
      amphipod transport, possibly in detached sponge fragments, could generate the
      high levels of overall gene flow observed. However, this transport mechanism
      appears much less effective across deep water as connectivity between Florida and
      Belize (1072 km) is highly restricted.

PMID- 17181730
TI  - Genetic polyandry and sexual conflict in the sandbar shark, Carcharhinus
      plumbeus, in the western North Atlantic and Gulf of Mexico.
AB  - To investigate patterns of polyandry in the sandbar shark (Carcharhinus
      plumbeus), 20 pregnant females were sampled from the western North Atlantic and
      Gulf of Mexico. Five species-specific microsatellite markers were used to
      genotype each shark and its litter. Of 20 litters, 17 (85%) were shown to have
      multiple sires. In multiply sired litters, the estimated minimum number of sires
      ranged from two to five with an average of 2.3 males per litter. Regression
      analysis did not demonstrate a significant relationship between female
      reproductive success and female body size or sire number and female body size.
      There was a high incidence of reproductive skew noted in litters, and two groups
      of males with significantly different mean reproductive success were observed.
      Analyses using Bateman's principles suggest that there is less direct benefit for
      females that acquire multiple mates than for males who bias paternity within
      litters. In light of past morphological and behavioural studies, these data
      suggest that patterns of polyandry in elasmobranchs may be determined by coercive
      mating, and that breeding behaviour has likely evolved in the context of sexual
      conflict.

PMID- 17181731
TI  - Does soil type drive social organization in southern hairy-nosed wombats?
AB  - Spatiotemporal distributions of key resources are hypothesized to underpin
      sociobiological patterns. Burrow availability and quality is of paramount
      importance to fossorial animals. The southern hairy-nosed wombat (Lasiorhinus
      latifrons) burrows in both hard and friable soils. Theoretical and empirical
      studies suggest that the harder substrate should promote closer geographical
      clustering of burrows than in softer soils. Clustered burrows are expected to be
      associated with larger group sizes. If sociality is driven by constraint rather
      than advantage, patterns of spatial and temporal distribution of animals within
      and among groups may show indications of avoidance or even antagonism, and
      'making the best of a bad job' via positive kin associations to offset the
      disadvantages of high-density living. To test these ideas, we compared warren
      relatedness and social structure of L. latifrons on friable soils (Nullarbor
      Plain) and hard calcrete (Brookfield Conservation Park, BCP). Individuals were
      sampled by noninvasive collection of hairs for genotyping to identify individuals
      and to estimate their space-use and associative behaviour with respect to
      relatedness. Burrows in calcrete were indeed more clumped, and warren and group
      size larger. Differences in spatiotemporal organization and relatedness structure
      between sites were in the expected direction: (i) Nullarbor males associated and
      shared warrens less than at BCP; and (ii) Nullarbor spatial relatedness
      patterning data were not consistent with proposed female breeding dispersal, in
      contrast to those at BCP. Under Nullarbor (low density) conditions, cooperation
      or tolerance between males may be less advantageous, and accessing or digging
      burrows should be less of a constraint for juvenile females.

PMID- 17181732
TI  - Population genetic signatures of diffuse co-evolution between leaf-cutting ants
      and their cultivar fungi.
AB  - Switching of symbiotic partners pervades most mutualisms, despite mechanisms that
      appear to enforce partner fidelity. To investigate the interplay of forces
      binding and dissolving mutualistic pairings, we investigated partner fidelity at
      the population level in the attine ant-fungal cultivar mutualism. The ants and
      their cultivars exhibit both broad-scale co-evolution, as well as cultivar
      switching, with short-term symbiont fidelity maintained by vertical transmission
      of maternal garden inoculates via dispersing queens and by the elimination of
      alien cultivar strains. Using microsatellite markers, we genotyped cultivar fungi
      associated with five co-occurring Panamanian attine ant species, representing the
      two most derived genera, leaf-cutters Atta and Acromyrmex. Despite the presence
      of mechanisms apparently ensuring the cotransmission of symbiont genotypes,
      different species and genera of ants sometimes shared identical fungus garden
      genotypes, indicating widespread cultivar exchange. The cultivar population was
      largely unstructured with respect to host ant species, with only 10% of the
      structure in genetic variance being attributable to partitioning among ant
      species and genera. Furthermore, despite significant genetic and ecological
      dissimilarity between Atta and Acromyrmex, generic difference accounted for
      little, if any, variance in cultivar population structure, suggesting that
      cultivar exchange dwarfs selective forces that may act to create co-adaptive ant
      cultivar combinations. Thus, binding forces that appear to enforce host fidelity
      are relatively weak and pairwise associations between cultivar lineages and ant
      species have little opportunity for evolutionary persistence. This implicates
      that mechanisms other than partner fidelity feedback play important roles in
      stabilizing the leafcutter ant-fungus mutualism over evolutionary time.

PMID- 17181733
TI  - Dispersal ecology versus host specialization as determinants of ectoparasite
      distribution in brood parasitic indigobirds and their estrildid finch hosts.
AB  - Brood parasitic birds offer a unique opportunity to examine the ecological and
      evolutionary determinants of host associations in avian feather lice
      (Phthiraptera). Brood parasitic behaviour effectively eliminates vertical
      transfer of lice between parasitic parents and offspring at the nest, while at
      the same time providing an opportunity for lice associated with the hosts of
      brood parasites to colonize the brood parasites as well. Thus, the biology of
      brood parasitism allows a test of the relative roles of host specialization and
      dispersal ecology in determining the host-parasite associations of birds and
      lice. If the opportunity for dispersal is the primary determinant of louse
      distributions, then brood parasites and their hosts should have similar louse
      faunas. In contrast, if host-specific adaptations limit colonization ability,
      lice associated with the hosts of brood parasites may be unable to persist on the
      brood parasites despite having an opportunity for colonization. We surveyed lice
      on four brood parasitic finch species (genus Vidua), their estrildid finch host
      species, and a few ploceid finches. While Brueelia lice were found on both
      parasitic and estrildid finches, a molecular phylogeny showed that lice infesting
      the two avian groups belong to two distinct clades within Brueelia. Likewise,
      distinct louse lineages within the amblyceran genus Myrsidea were found on
      estrildid finches and the parasitic pin-tailed whydah (Vidua macroura),
      respectively. Although common on estrildid finches, Myrsidea lice were entirely
      absent from the brood parasitic indigobirds. The distribution and relationships
      of louse species on brood parasitic finches and their hosts suggest that host
      specific adaptations constrain the ability of lice to colonize new hosts, at
      least those that are distantly related.

PMID- 17181734
TI  - Relationship between cancer and oral pemphigoid patients with antibodies to
      alpha6-integrin.
AB  - BACKGROUND: Mucous membrane pemphigoid is an autoimmune mucocutaneous blistering
      disease. A subset, known as anti-epiligrin cicatricial pemphigoid is associated
      with a high risk for malignancy. Oral pemphigoid (OP) is limited to the oral
      cavity. The purpose of this study was to determine the association between
      malignancy and patients with OP with antibodies to alpha6-integrin subunit.
      METHODS: We determined the incidence of cancer in 72 patients with OP and
      compared it to the expected incidence using age and sex-specific rates of
      malignancy in the National Cancer Institute's Surveillance, Epidemiology, and End
      Results (NCI SEER) Registry. RESULTS: During a mean observation period of 9.1
      years (range: 2.8-40), for 70, three OP patients developed malignancies. The
      expected number of cancers based on the NCI SEER Registry was 8.83. The relative
      risk for cancer in OP patients, with autoantibodies to alpha6-integrin, was 0.34
      (95% CI, 0.07-0.99, P < 0.05). CONCLUSION: It appears that patients with OP, with
      antibodies to alpha6, may have a possible reduced relative risk for developing
      cancer.

PMID- 17181736
TI  - Oral submucous fibrosis: study of 1000 cases from central India.
AB  - BACKGROUND: Very few reports have been published on the gender specificity of
      oral submucous fibrosis (OSF) in relation to habit patterns and the severity of
      disease in the world literature. The purpose of the study was to ascertain the
      gender specificity for different habits and severity of OSF. METHODS: A hospital
      based cross-sectional study on various habit patterns associated with OSF was
      performed in Nagpur over a 5-year period. A total of 1000 OSF cases from 266,418
      out patients comprised the study sample. RESULTS: The male-to-female ratio of OSF
      was 4.9:1. Occurrence of OSF was at a significant younger age group (<30 years)
      among men when compared with women (OR = 4.62, 3.22-6.63, P = 0.0001). Reduced
      mouth opening, altered salivation and altered taste sensation were found to be
      significantly more prevalent in women when compared with men. Exclusive areca nut
      chewing habit was significantly more prevalent in women (OR = 44.5, 25.4-79.8, P
      = 0.0001). Whereas significant increase for Gutkha (Areca quid with tobacco) (OR
      = 2.33, 1.56-3.54, P = 0.0001) and kharra/Mawa (crude combination of areca nut
      and tobacco) (OR = 6.8, 4.36-11.06, P = 0.0001) chewing was found in men when
      compared with women. CONCLUSIONS: There is a marked difference in literacy,
      socioeconomic status, areca nut chewing habits, symptoms and disease severity in
      women when compared with men in the central Indian population.

PMID- 17181735
TI  - A quantitative co-localization analysis of large unspliced tenascin-C(L) and
      laminin-5/gamma2-chain in basement membranes of oral squamous cell carcinoma by
      confocal laser scanning microscopy.
AB  - BACKGROUND: A structural interaction of the oncofetal large tenascin-C splice
      variants (Tn-C(L)) and the gamma2-chain of laminin-5 (Ln-5/gamma2) was recently
      demonstrated in oral squamous cell carcinoma (OSCC). In situ different patterns
      of co-localization and co-deposition of both proteins could be detected.
      Especially the co-localization in re-established basement membrane (BM)
      structures seemed to be biologically meaningful within the process of tumour
      progression. METHODS: The amount of Tn-C(L) incorporated in reorganized OSCC BM
      structures at the tumour margins was investigated by a laser scanning microscopy
      based quantitative co-localization analysis. RESULTS: In the BM of normal oral
      mucosa no Tn-C(L) could be detected. In dysplastic and neoplastic oral mucosa a
      distinct co-localization of Tn-C(L) and Ln-5/gamma2 in the BM region could be
      observed. The extent of Tn-C(L) arrangement into reorganized BM structures
      correlated with malignancy grade. CONCLUSIONS: The results suggest at first, a
      modulation of carcinomatous BM structures by the inclusion of oncofetal matrix
      proteins during tumour progression and secondly, the BM incorporation of the
      adhesion-modulating molecule Tn-C(L) as a pre-invasive structural phenomenon in
      OSCC.

PMID- 17181737
TI  - Highly sensitive detection of HPV-DNA in paraffin sections of human oral
      carcinomas.
AB  - BACKGROUND: Although human papillomavirus (HPV) infection has been shown to be a
      significant carcinogen in cervical squamous cell carcinoma (SCC), its
      significance in oral SCC remains unclear. METHODS: We developed highly sensitive
      detection methods for HPV to elucidate the prevalence and localization of HPV in
      paraffin sections from human oral SCC using modified in situ polymerase chain
      reaction (PCR) and in situ hybridization AT tailing (ISH-AT). Analyses revealed a
      high prevalence of several HPV types (HPV-16, -18, -22, -38 and -70) under
      optimal conditions. The ISH-AT method can be used as an alternative to in situ
      PCR. RESULTS: Various staining patterns were observed in the 20 cases examined,
      and HPV-positive cells were localized within the surface epithelium as well as in
      neoplastic cells. We demonstrated that HPV-DNA could be detected in paraffin
      sections using either the method of in situ PCR or ISH, providing an appropriate
      primer and probe are used. CONCLUSION: These results suggest that HPV infection
      could be one of several risk factors being involved in oral SCC.

PMID- 17181738
TI  - Malignant transformation in 1458 patients with potentially malignant oral mucosal
      disorders: a follow-up study based in a Taiwanese hospital.
AB  - BACKGROUND: It is generally accepted that the development of cancer in the oral
      mucosa is preceded by an identifiable non-invasive precursor lesion. The aim of
      this follow-up study was to estimate the rate and the time to transformation in a
      group of patients from southern Taiwan with potentially malignant oral epithelial
      lesions. METHODS: The follow-up time is defined as the duration between the onset
      of the initial diagnosis and the occurrence of confirmed oral cancer. A total of
      1458 patients with histological diagnoses of various pre-malignant oral lesions
      were followed up between 1991 and 2001. The average age at initial diagnosis was
      47.5 years. The histological diagnoses were divided into six categories:
      epithelial dysplasia with hyperkeratosis/epithelial hyperplasia (8.85%);
      epithelial dysplasia with submucous fibrosis (2.54%); submucous fibrosis
      (27.57%); hyperkeratosis/epithelial hyperplasia (29.01%); lichen planus (9.80%)
      and verrucous hyperplasia (22.22%). RESULTS: Within the cohort of 1458 patients,
      44 patients progressed to oral cancer in the same site as the initial lesions
      with an overall transformation rate of 3.02% and a mean follow-up time of 42.64
      months. Eight of the 166 patients with dysplastic lesions and 15 of 423 patients
      with hyperkeratosis/epithelial hyperplasia progressed to malignancy. The other
      patients with malignant transformation originated from various pre-cancerous oral
      lesions and conditions (submucous fibrosis, eight of 402; lichen planus, three of
      143; verrucous hyperplasia, 10 of 324). CONCLUSION: These results indicate that
      patients with pre-malignant oral lesions need long-term follow up.

PMID- 17181739
TI  - Osteopontin as biomarker in early invasion by squamous cell carcinoma in tongue.
AB  - BACKGROUND: Osteopontin (OPN) expression in squamous cell carcinoma (SCC) of the
      tongue has not been clearly elucidated. METHODS: We selected 46 cases of tongue
      SCC and investigated the expression of OPN by immunohistochemical staining. The
      immunopositive reaction and score for each case were semiquantitatively
      evaluated. RESULTS: Scores were significantly higher in carcinoma nests than in
      neighboring normal epithelium or epithelial dysplasia. The OPN was expressed
      clearly in the cytoplasm of carcinoma cells. In cases of early invasive
      carcinoma, in particular, expression of OPN showed a remarkable increase at the
      invasion front compared with the non-invaded regions. However, there was no
      significant correlation between expression of OPN in the primary tumor nest and
      lymphatic metastasis, recurrence, or survival rate. CONCLUSION: This suggests
      that OPN is a useful biomarker of early invasion by SCC in tongue.

PMID- 17181740
TI  - Collagen XVIII modulation is altered during progression of oral dysplasia and
      carcinoma.
AB  - BACKGROUND: Collagen XVIII is a ubiquitous basement membrane (BM) component and a
      precursor of endostatin. METHODS: Using immunohistochemistry and in situ
      hybridization, we studied the expression and localization of collagen XVIII in
      different stages of normal oral wound healing, epithelial dysplasia and squamous
      cell carcinoma (SCC). RESULTS: In mild epithelial dysplasias collagen XVIII
      appeared as a continuous signal in the BM, whereas in severe epithelial
      dysplasias and in the invasive areas of oral SCCs collagen XVIII was absent. In
      situ hybridization showed that collagen XVIII mRNA expression did not decrease in
      severe dysplasia or oral carcinoma samples when compared with the mild
      dysplasias. CONCLUSIONS: The results indicate that the absence of collagen XVIII
      protein in severe oral dysplasias is related to the processing of the protein
      rather than to changes in mRNA expression.

PMID- 17181741
TI  - MICA and MICB overexpression in oral squamous cell carcinoma.
AB  - BACKGROUND: The concentration of MICA in serum seems be a good candidate marker
      in cancer. Previous studies from our laboratory have shown that the polymorphic
      MIC gene may confer a risk for oral squamous cell carcinoma (OSCC). The study
      investigated the expression levels of MICA and MICB of OSCC patients and cancer
      cell lines. MATERIAL AND METHODS: We used RT-PCR to analyze the mRNA expression
      of MICA and MICB in four oral cancer cell lines compared with three normal human
      oral keratinocyte (NHOK) cell lines and in tissues from 36 patients with OSCC
      comparing tumor tissue with non-cancerous matched tissue (NCMT). RESULTS:
      Endogenous MICB mRNA expression in OSCC cell lines was significantly higher than
      that in NHOK (1.40 +/- 0.27 vs. 0.40 +/- 0.16; P = 0.04). In 20 of 36 sets of
      tissue from patients with OSCC, MICB mRNA expression was higher in the cancerous
      tissue than in the NCMT. The mean MICB mRNA expression in OSCC tissues was
      significantly higher than in NCMT (0.39 +/- 0.08 vs. 0.14 +/- 0.03, P = 0.009,
      paired t-test). A significantly lower MICA mRNA was found in patients who chewed
      areca nut compared with those who did not use areca (P = 0.001) and in patients
      with well-differentiated tumors compared with those with less well-differentiated
      tumors (P = 0.02). CONCLUSION: MICA and MICB mRNA expression may be increased in
      OSCC but there appears to be individual variation.

PMID- 17181742
TI  - Claudins 1, 4, 5, 7 and occludin in ameloblastomas and developing human teeth.
AB  - BACKGROUND: To analyze the distribution pattern of claudins 1, 4, 5, 7 and
      occludin in benign and malignant ameloblastomas and developing human teeth.
      METHODS: Paraffin-embedded tissue specimens of 25 benign and four malignant
      ameloblastomas and two developing human teeth were examined immunohistochemically
      using antibodies against claudins 1, 4, 5, 7 and occludin. RESULTS: In
      ameloblastomas strongest expression was seen for claudins 1 and 7 while claudin 4
      was expressed less frequently. Claudin 5 and occludin were seen only in a
      minority of cases. There were no evident differences in the expression of
      claudins or occludin neither between different histologic subtypes of
      ameloblastomas nor between benign or malignant cases. The strongest expression
      for claudins was present in the central stellatum reticulum-like cells
      surrounding the microcysts and in the areas with squamous differentiation of the
      ameloblastomas. In developing teeth both claudin 1 and 7 stained strongly in the
      enamel epithelium, ameloblasts, and enamel matrix, but staining for claudin 4 was
      relatively weak. Claudin 5 was preferentially expressed only in vessels, and
      occludin staining ranged from negative to weak in ameloblastomas and teeth germs.
      CONCLUSION: There were no clear differences in the expression levels between
      benign and malignant ameloblastic tumors. The overexpression of claudins in the
      areas with microcyst formation may indicate their attempt to maintain the
      interepithelial cohesion of the cells. The strong immunoreactivity of ameloblasts
      and newly synthesized enamel matrix for claudins 1 and 7 indicates that they may
      be involved in cell signaling influencing enamel formation.

PMID- 17181743
TI  - Hereditary benign intraepithelial dyskeratosis: a new case?
AB  - Hereditary benign intraepithelial dyskeratosis (HBID) is a rare disorder first
      described in 1960. To date, all but one published case trace their ancestry back
      to an Indian tribe in North Carolina. Affected patients usually develop
      asymptomatic ocular and oral lesions. The latter may resemble other dermatologic
      conditions that affect the oral mucosa, such as white sponge nevus. This report
      describes a case of a Brazilian patient who showed clinical and histological
      features of HBID, which appears to be the first reported case in South America.
      Although genetic analysis could not be carried out, the family history suggests a
      genetic etiology.

PMID- 17181744
TI  - Rhabdomyomatous (mesenchymal) hamartoma of the tongue: report of a case.
AB  - A 12-year-old girl presented with three yellowish polypoid lesions in the lateral
      border of tongue since birth. Histological examination showed oral mucosa covered
      by squamous epithelium and an underlying vascularized fibrous stroma, containing
      small and short bundles of striated muscle, corresponding to a rhabdomyomatous
      hamartoma.

PMID- 17181745
TI  - Concrescence of teeth: cemental union between the crown of an impacted tooth and
      the roots of an erupted tooth.
AB  - Concrescence of teeth is a condition showing a union of adjacent teeth by only
      cementum. In all the previously reported cases, the union has been observed
      between the roots of the affected teeth. Here, we describe the first case that
      showed a concrescence of the crown of an impacted tooth and the roots of the
      erupted tooth. In addition, we discuss how this condition, especially the
      deposition of acellular cementum on the crown, occurred.

PMID- 17181747
TI  - Communication skills in blind children: a preliminary investigation.
AB  - BACKGROUND: There are anecdotal reports that blind children sometimes use
      language inappropriately, but there has been no recent systematic investigation
      of the communication skills of children with congenital blindness. The aim of the
      present study was to conduct a preliminary investigation of the communication
      skills of a group of children with congenital blindness. METHODS: The parents of
      eight congenitally blind children completed the Children's Communication
      Checklist-2. RESULTS: The checklist ratings showed that the communication
      profiles of a large proportion of the group warranted clinical investigation or
      were indicative of a communication disorder. CONCLUSIONS: The results from this
      preliminary investigation support the need for a larger study on the
      communication skills of children with congenital blindness.

PMID- 17181748
TI  - Associations of motor co-ordination and attention with motor-perceptual
      development in 3-year-old preterm and full-term children who needed neonatal
      intensive care.
AB  - BACKGROUND: Children who have needed neonatal intensive care (NIC) are considered
      to be at risk for deficits such as developmental co-ordination disorder and
      attention-deficit/hyperactivity disorder. By assessing motor-perceptual
      development, motor co-ordination and attention already at 3 years of age, it
      might be possible to identify such deficits earlier than they are today. AIM: To
      investigate the motor-perceptual development in a group of 202 NIC children but
      had no major impairments, to describe associations of deficits in co-ordination
      and attention with motor-perceptual delays, and to estimate the prevalence of NIC
      children with combined deficits together with a motor-perceptual delay. METHOD:
      Co-ordination and attention in children born very preterm (n = 57), moderately
      preterm (n = 75) and full-term (n = 70) were observed according to a model for
      Combined Assessment of Motor Performance and Behaviour while they were assessed
      using a developmental scale, Motor-Perceptual Development, 0-7 years, MPU.
      RESULTS: In two out of 14 MPU areas, a larger proportion of very preterm than of
      moderately preterm and full-term children had marked developmental delay.
      Overall, the proportion of NIC children having a motor-perceptual delay increased
      with increasing incoordination and especially increasing lack of attention.
      Twenty-one (11%) of the NIC children had different motor-perceptual delays
      combined with pronounced incoordination and pronounced lack of attention.
      CONCLUSION: Deficits in co-ordination and attention were associated with motor
      perceptual delays in areas important for daily living and development of academic
      skills. Therefore, to find children at risk for developmental co-ordination
      disorder and attention-deficit/hyperactivity disorder, assessments of co
      ordination and attention should be added to assessments of motor-perceptual
      development in 3-year-old NIC children.

PMID- 17181749
TI  - The relationship between gross motor function and participation restriction in
      children with cerebral palsy: an exploratory analysis.
AB  - BACKGROUND: Children with cerebral palsy (CP) experience a variety of functional
      limitations depending on the severity of their condition that impact on their
      participation in day-to-day activities. METHODS: The gross motor function and
      participation restrictions experienced by 60 ambulant children with CP (mean age
      11.04 years) were assessed using the Gross Motor Function Measure (GMFM-88) and
      the Lifestyle Assessment Questionnaire - Cerebral Palsy (LAQ-CP). RESULTS: A
      significant negative correlation existed between the GMFM-88 and the LAQ-CP (r = 
      0.52, P < 0.001). Significant relationships were also identified between the GMFM
      88 and the physical independence, mobility, economic burden and social
      integration domains of the LAQ-CP. CONCLUSION: In ambulatory children with CP,
      better physical function is associated with a lesser impact of disability;
      however, the relationship between function and participation is complex. Measures
      of participation restriction may assist with goal setting appropriate to the
      specific needs of the child and family.

PMID- 17181750
TI  - Measuring children's participation in recreation and leisure activities:
      construct validation of the CAPE and PAC.
AB  - There is a need for psychometrically sound measures of children's participation
      in recreation and leisure activities, for both clinical and research purposes.
      This paper provides information about the construct validity of the Children's
      Assessment of Participation and Enjoyment (CAPE) and its companion measure,
      Preferences for Activities of Children (PAC). These measures are appropriate for
      children and youth with and without disabilities between the ages of 6 and 21
      years. They provide information about six dimensions of participation (i.e.
      diversity, intensity, where, with whom, enjoyment and preference) and two
      categories of recreation and leisure activities: (i) formal and informal
      activities; and (ii) five types of activities (recreational, active physical,
      social, skill-based and self-improvement). This paper presents information about
      the performance of the CAPE and PAC activity type scores using data from a study
      involving 427 children with physical disabilities between the ages of 6 and 15
      years. Intensity, enjoyment and preference scores were significantly correlated
      with environmental, family and child variables, in expected ways. Predictions
      also were supported with respect to differences in mean scores for boys vs.
      girls, and children in various age groups. The information substantiates the
      construct validity of the measures. The clinical and research utility of the
      measures are discussed.

PMID- 17181752
TI  - Children injured following TV tipovers in Israel, 1997-2003.
AB  - BACKGROUND: According to the US Consumer Product Safety Commission, about 7000
      children, many under age five, are treated annually at emergency rooms for
      injuries associated with unintentional tipping of television (TV) and furniture.
      However, the professional literature does not reflect much inquiry regarding this
      source of risk. In Israel, cases of children injured following TV tipover are
      reported in newspapers but no studies were conducted in Israel on this issue. The
      aim of this report is to present data regarding frequency and characteristics of
      children injured following a falling TV in Israel during recent years, in order
      to provide more specific information for advising policymakers and raising
      awareness about this growing danger. METHODS: Data were obtained from the Israeli
      National Trauma Registry, and included injured children (0-17) hospitalized
      between 1997 and 2003, because of TV-related injury. Demographic information,
      Injury Severity Score (ISS), injured body region, surgical intervention,
      admission to the intensive care unit, length of hospital stay, destination at
      discharge and mortality were analysed. RESULTS: There were 116 children injured
      following TV tipover during the years analysed, increasing from nine in 1997 to
      27 in 2003. Over half of the children (54.3%) were aged 1-2 years; 57.8% were
      boys. Three-quarters of the TV-related injuries were head and neck injuries;
      nearly one-fifth had ISS scores of over 15. The mean was 4.3 (median = 2 days);
      15 children (12.9%) required surgery and four children died in the hospital.
      CONCLUSION: The findings reflect the fact that TV tipover is a growing source of
      danger that can be serious and should be brought to the attention of the public,
      health professionals and policymakers. Specific, age-related recommendations
      should be proposed, such as placing TVs on low and stable surface and not placing
      the remote controls on the top of the set.

PMID- 17181751
TI  - A matched case-control study: investigating the relationship between youth assets
      and sexual intercourse among 13- to 14-year-olds.
AB  - BACKGROUND: The number of teenagers engaging in sexual intercourse has
      consistently changed over the past several years. This can become a major
      challenge when trying to determine why teens continue to have sex. The purpose of
      this paper was to investigate the relationship between youth assets and sexual
      intercourse among 13- to 14-year-olds. METHODS: Cross-sectional data were
      collected using in-person at-home interviews from a random sample of inner-city
      neighbourhood 13- to 14-year-old teenagers (n = 64 matched pairs; 36% 13-year
      olds, 53% female, 45% white, 28% African-American, 16% Hispanic and 11% Native
      American). Nine individual youth assets were analysed using conditional logistic
      regression (matching for several demographic variables) to assess the association
      between assets and abstinence in younger teens. RESULTS: Conditional logistic
      regression analyses showed that two assets, positive Peer Role Models [odds
      ratios (OR) = 4.67, 95% confidence intervals (CI) = 1.93, 11.27] and Use of Time
      (Religion) (OR = 2.20, 95% CI = 1.04, 4.65), were significantly related (P <
      0.05) to younger teens never having engaged in sexual activity. CONCLUSION: These
      findings suggest, when considering abstinence behaviour, involvement in religious
      activities and having positive peer role models appear to be protective factors
      related to delaying sexual intercourse among teens aged 13-14 years.

PMID- 17181753
TI  - Looking after well siblings of adolescent girls with anorexia: an important
      parental role.
AB  - BACKGROUND: Research has suggested that well siblings of children with chronic
      and life-threatening illnesses are at risk for negative outcomes and that
      parents' responses to the illnesses can influence the adaptation of well
      siblings. Yet, parents' efforts to look after well siblings in the context of
      illness are rarely considered in literature about sibling adaptation. The
      importance of attending to the needs of well siblings was a major theme to emerge
      from a qualitative analysis of the experiences of parents of adolescent girls
      with anorexia nervosa. METHODS: In-depth interviews were conducted with 24
      parents of adolescent girls with anorexia and analysed using grounded theory
      method. RESULTS: The data indicated that parents viewed caring for well siblings
      in the context of anorexia as an important role and responsibility. Parents
      reported making conscious and active efforts to look after well siblings by:
      maintaining normality; compensating for changes to routines; protecting siblings;
      providing emotional support; and managing the consequences. CONCLUSIONS: This
      paper provides a picture of the actions parents take to help well siblings adapt
      to anorexia in the family. Further research is needed to develop and expand this
      understanding to families experiencing a wide range of chronic and life
      threatening illnesses. The findings underline the importance of clinical
      attention and further research into the critical parental role of caring for well
      siblings.

PMID- 17181754
TI  - Cross-sectional comparison of physical activity and inactivity patterns in
      Chinese and Filipino youth.
AB  - BACKGROUND: To compare and contrast youth physical activity (PA) and inactivity
      patterns in two developing Asian countries: the Philippines and China. METHODS:
      Comparative analysis of 1997-1999 Cebu Longitudinal Health and Nutrition Survey
      and the 1997 China Health and Nutrition Survey, large-scale surveys that included
      questions on type, frequency and duration of: commuting mode to school,
      sports/exercise in and outside of school, select sedentary activities and chores.
      RESULTS: Filipino data included 760 males and 872 females aged 14-16 years. The
      comparable Chinese sample consisted of 202 males and 197 females. Active
      commuting is proportionately high in both countries (70-71% in the Philippines
      vs. 77-90% in China), although commuting by bicycling is rare in the Philippines
      (<1%) vs. China ( approximately 35%). Patterns of school sport/exercise
      participation differ between countries by gender; more Filipino males report
      school sport/exercise than females (63 vs. 49%) vs. China, where more females
      participate than males (75 vs. 69%). Sport/exercise outside of school is
      proportionately low (6-12%) for youth from both countries with a single
      exception: 74% of Filipino males participate in extra-curricular sport/exercise.
      Although a higher percentage of Filipino youth report watching television >4
      h/day (<10%) vs. Chinese youth (<1%), both are lower than comparable US reports.
      CONCLUSION: In the Philippines, continued modernization augurs a decrease in
      local primary PA sources (chores and active commuting). In China, where youth
      already are not expected to perform chores, shifts to more passive commuting
      modes (i.e. increased motorized transportation) are anticipated.

PMID- 17181755
TI  - Paths to child social adjustment: parenting quality and children's processing of
      social information.
AB  - BACKGROUND: The purpose of this research was to examine the manner in which
      multiple influences on child social adjustment operated together to predict
      differential outcomes for young children. Specifically, this study was designed
      to (i) examine the role of social cognitive and emotional factors in parents'
      observed and self-reported behaviour towards their children, and (ii) investigate
      the impact of parenting and children's social information processing (SIP)
      patterns on children's subsequent social adjustment in the school setting.
      METHODS: A model of children's peer social adjustment was evaluated using a group
      of 166 children, over-sampled for history of physical child abuse. Assessment of
      constructs was multi-method, including parent and child self-reports as well as
      teacher reports of child adjustment and observations of parent-child and child
      peer interactions. RESULTS: Using structural equation modelling, support was
      found for our theoretical model. Specifically, parents' negative child-related
      beliefs and clinical elevations in emotional distress were predictors of harsh,
      insensitive parenting, which in turn predicted children's SIP operations and
      social maladjustment 6 months later. However, children's SIP did not
      significantly predict their social adjustment above and beyond the impact of
      parenting. CONCLUSIONS: Results indicated that the quality of parenting that
      children received was more central to subsequent adjustment in peer interactions
      than were children's SIP operations. Furthermore, the quality of parenting
      children experienced was closely linked to parents' beliefs about their children
      and parents' mental health status. Directions for future research and potential
      implications for clinical practice are discussed.

PMID- 17181756
TI  - Child consent and the law: an insight and discussion into the law relating to
      consent and competence.
AB  - BACKGROUND: The law governing consent for children is not very clear. A child can
      consent to treatment but usually in practice is unable to refuse it. Even if both
      the child and parents refuse treatment, courts are reluctant to accept this,
      particularly if it is in the best interest of the child. DISCUSSION: In order to
      consent to treatment, a child must be competent enough to do so, and this
      competence is judged usually by a doctor. Children can even consent to
      contraceptives and abortion if 'competent' to do so. This concept perfectly lacks
      moral, ethical and emotional competence, and judgement of competence is carried
      out usually purely scientifically by pure science-orientated objective
      professionals like doctors. A broad discussion about the issues of children
      refusing treatment is conducted from the legal, ethical and philosophical point
      of view. Life-saving treatment and various other cases are also discussed.
      CONCLUSION: There is no right answer to the question. A more holistic approach is
      needed, and not only doctors but also sociologists, care specialists and even
      clergymen should be asked to judge competence in a multidisciplinary environment,
      particularly for contraceptives and abortion. This multidisciplinary working can
      be extended to other areas in medical law as well particularly in light of
      changes in medicine. Experience in life should be valued in a decision-making
      environment for judging competence. The law in relation to child consent is
      unclear and requires changes in order to clarify what is perceived as the child's
      best interest.

PMID- 17181757
TI  - A qualitative investigation of school-aged children's answers to items from a
      generic quality of life measure.
AB  - BACKGROUND: The development of instruments to measure child self-reported quality
      of life (QOL) is dependent on whether children can understand the concepts behind
      items. Researchers need more information on how children are interpreting and
      answering items. This paper aims to investigate the strategies school-aged
      children use to answer QOL items. METHODS: A generic 30-item QOL measure (the
      TedQL) was administered to 266 healthy children (5-6, 7-9 years old). Children
      were asked to 'think aloud' while answering a selection of 10 TedQL items (n = 4
      ability, n = 4 social, n = 2 mood items), and their responses were recorded
      verbatim. RESULTS: The strategies children reported using when answering items
      were coded into five categories: (1) social comparisons; (2) stable character
      references; (3) concrete examples; (4) other reasons; or (5) no reason given.
      Concrete examples were used most frequently by children. Strategy type was
      dependent on age, with 7-9-year-olds reporting social comparisons and concrete
      examples more frequently than 5-6-year-olds. Five-to-six-year-olds gave no
      reasons for their response choices more frequently than 7-9-year-olds. Strategy
      type also differed by item type, with social comparisons used more frequently for
      ability items, and stable character references for social items. However,
      concrete examples were used consistently highly across ability and social items.
      CONCLUSIONS: Children aged 5-9 years most commonly report using concrete examples
      of specific instances when answering QOL items. However, strategy use varies as a
      function of age and types of items. Our results highlight the importance of
      keeping in mind children's developmental age when interpreting responses from
      child QOL instruments.

PMID- 17181758
TI  - Listen to me, too! Lessons from involving children with complex healthcare needs
      in research about multi-agency services.
AB  - BACKGROUND: Children with complex healthcare needs are often excluded, both from
      active involvement in research projects and from direct consultation in services.
      During a 3-year research study into multi-agency services for children with
      complex healthcare needs, the authors involved children in a number of innovative
      ways and endeavoured to discover what impact, if any, multi-agency working made
      to them. METHODS: The researchers 'spent time' with 18 children with complex
      healthcare needs. They used a variety of methods to engage with the children in a
      meaningful way. More than half of the children had no verbal communication, so it
      was necessary in some cases to work with an advocate, usually the parent, to aid
      the process. RESULTS: Children with complex healthcare needs can take part in
      research as long as the research is set up sensitively and flexibly. In terms of
      the impact of multi-agency working, the authors concluded significant advances
      had been achieved for this group: almost all the children were living at home and
      attending school. However, there were significant gaps in addressing children's
      human rights in relation to communication, independence and relationships. In
      addition, many of the children had very little effective direct consultation with
      the multi-agency services. CONCLUSIONS: There are significant advances in
      involving disabled children in research and in service delivery, but there is
      still some way to go in involving those with complex healthcare needs. The
      challenges are considerable, but the benefits far outweigh these, not least being
      the value that parents, carers and the children themselves place upon being
      listened to.

PMID- 17181759
TI  - A pilot study to compare the use of prototypes of multipositional paediatric
      walking sticks and tripods with conventional sticks and tripods by children with
      cerebral palsy.
AB  - BACKGROUND: The researchers (B.H. and B.T.) designed prototypes of a walking
      stick and a tripod termed Multipositional Paediatric Walking Aids for children
      with cerebral palsy (CP). The design won the 'Jenx Award for Innovation in
      Paediatric Physiotherapy'. The object of this study was to ascertain whether the
      prototypes had any benefit over conventional designs in children with CP.
      METHODS: A small case series within-subject comparison design was used. There
      were four periods, AABA, each 4 weeks in length. Prototypes were used during
      period B. Eight children with CP between 4 and 11 years were recruited, four used
      sticks and four used tripods. Following an orthopaedic assessment, each child had
      assessments at the commencement of the study and every 4 weeks thereafter: (1)
      Energy used while walking using Physiological Cost Index (PCI). (2) Motor
      abilities using (a) Gross Motor Function Measure (GMFM-88) and (b) Gross Motor
      Performance Measure (GMPM). (3) Hand/forearm position recorded on a visual
      analogue. (4) Parent/child questionnaire. RESULTS: Physiological Cost Index
      improved overall when the prototypes were used suggesting the amount of energy
      used when walking with the prototypes was less than with conventional
      sticks/tripods. GMFM-88 and GMPM results improved for some but not all children.
      Results for PCI, GMFM and GMPM were not statistically significant. The
      hand/forearm position of stick users consistently improved at assessment 4.
      Questionnaire results indicated that stick users preferred the prototypes.
      CONCLUSION: Multipositional sticks/tripods may have benefits over conventional
      sticks/tripods. Children using sticks rather than tripods preferred the
      prototypes. The study demonstrates the need to undertake scientifically
      controlled trials before marketing new equipment.

PMID- 17181768
TI  - Do elite athletes experience low back, pelvic girdle and pelvic floor complaints
      during and after pregnancy?
AB  - The aim of the present investigation was to study prevalence of low back pain,
      pelvic girdle pain (PGP) and pelvic floor disorders during pregnancy and after
      childbirth in elite athletes. A postal questionnaire was sent to all elite
      athletes who had given birth registered with The Norwegian Olympic Committee and
      Confederation of Sports (n=40). Eighty age-matched women served as the control
      group. The response rates were 77.5% and 57.5% in the elite athletes and control
      groups, respectively. There were no significant differences in the prevalence of
      low back and PGP, urinary or fecal incontinence among elite athletes and controls
      at any time point. The prevalence of low back pain without radiation to the leg
      in elite athletes was 25.8%, 18.5%, 9.7% and 29% the year before pregnancy,
      during pregnancy, 6 weeks postpartum and at the time of completing the
      questionnaire, respectively. The prevalence of PGP was 0, 29.6%, 12.9% and 19.4%.
      Prevalence of stress urinary incontinence was 12.9%, 18.5%, 29% and 35.5%. None
      of the elite athletes had fecal incontinence at any time point. There were no
      differences in mode of delivery or birthweight between elite athletes and
      controls. The elite athletes had a significantly lower body mass index at 6 weeks
      postpartum and at present compared with the control group.

PMID- 17181769
TI  - Global changes in anaerobic fitness test performance of children and adolescents
      (1958-2003).
AB  - AIM: To quantify the global changes in anaerobic fitness (operationalized as
      power and speed test performance) of children and adolescents. METHODS: Following
      an extensive review of the literature, 32 studies examining secular changes in
      power and speed test performance of children and adolescents were analysed.
      Performance changes were calculated at the country x age x sex x test level using
      weighted least-squares regression, and were expressed as a percentage of the
      weighted mean value for all data points in the regression. Negative values
      indicated performance declines, and positive values indicated improvements.
      RESULTS: Changes in power (n=20 802 925) and speed (n=28 320 308) test
      performance were calculated for 6-19 year olds from 27 countries and five
      geographical regions, for the period 1958-2003. Overall, power and speed test
      performances improved at +0.03% and +0.04% per annum, respectively. Performance
      changes were remarkably similar for boys and girls, and children and adolescents,
      and somewhat similar for different geographical regions, and high and low income
      economies. The pattern of change was reasonably consistent over time. CONCLUSION:
      The relative stability in anaerobic fitness test performances in recent decades
      could be due to the negating effects of increases in fat mass and fat-free mass
      on anaerobic performance.

PMID- 17181770
TI  - Biomechanical analysis of anterior cruciate ligament injury mechanisms: three
      dimensional motion reconstruction from video sequences.
AB  - BACKGROUND: Methods for analyzing the mechanisms of injuries in sports from video
      sequences of injury situations are so far limited to a simple visual inspection,
      which has shown poor accuracy. PURPOSE: To investigate whether a new model-based
      image-matching technique could successfully be applied to estimate kinematic
      characteristics of three typical anterior cruciate ligament (ACL) injury
      situations. METHODS: A four-camera basketballvideo, a three-camera European team
      handball video and a single-camera downhill skiing video were imported into the
      program Poser 4, where a skeleton model and a model of the surroundings were
      matched to the background image frame by frame. When the match was considered
      satisfactory, joint angles as well as velocity and acceleration of the center of
      mass were calculated using Matlab. RESULTS: In the basketball and handball
      matchings, the skeleton and surrounding models were successfully matched to the
      background through all frames in all camera angles. Detailed time courses for
      joint kinematics and ground reaction force were obtained, while less information
      could be acquired from the single-view skiing accident. CONCLUSION: The model
      based image matching technique can be used to extract kinematic characteristics
      from videotapes of actual ACL injuries, and may provide valuable information on
      the mechanisms for ACL injuries in sports.

PMID- 17181771
TI  - Operative treatment of stress fractures of the proximal second metatarsal.
AB  - Proximal stress fractures of the second metatarsal are rare. They have been
      reported mainly in classical ballet dancers. Non-operative treatment has usually
      led to good results and rapid return to full activities. We present a series of
      nine cases with stress fractures of the proximal second metatarsal. The patients
      were all actively involved in sports. None of them were dancers. In all of these
      patients non-operative treatment lasting for an average of 13 months had failed.
      All of the patients were operated on using the same method. In the operation
      drilling was performed around and through the fracture line. The patients were
      followed for an average of 38 months. All except one of the patients were able to
      return to their prior level of activity within 4-6 months. In conclusion if non
      operative treatment fails surgery seems to give good results in most patients
      with a stress fracture of the proximal second metatarsal.

PMID- 17181772
TI  - Dynactin enhances the processivity of kinesin-2.
AB  - Kinesin-2 is a major microtubule-based motor in most cell types. Its in vitro
      motile properties have been analyzed extensively and been found to differ
      considerably from kinesin-1. Although recombinant kinesin-2 heterodimers exhibit
      processive movement, the processivity of the native kinesin-2 holoenzyme has
      never been evaluated. Kinesin-2 can interact with dynactin, a 'processivity
      factor' for cytoplasmic dynein, which may alter its motile properties. In this
      study, we analyze the in vitro motility of single native kinesin-2 molecules and
      determine the effects of dynactin on motor processivity. We find that individual
      native kinesin-2 molecules travel processively. Dynactin has no effect on
      velocity but significantly increases the run length of kinesin-2 movements. These
      results show that the interaction with dynactin has important functional
      consequences on the activity of the kinesin-2 motor.

PMID- 17181773
TI  - Tetraspanins as regulators of protein trafficking.
AB  - Small transmembrane proteins of the tetraspanin superfamily are believed to
      function as the main structural blocks of specialized membrane microdomains
      (referred to as tetraspanin-enriched microdomains, TERM or TEM). Through a
      multitude of homotypic and heterotypic interactions, tetraspanins regulate
      lateral clustering and, consequently, signalling involving adhesion and growth
      factor receptors as well as costimulatory proteins. The presence of major
      histocompatibility complex (MHC) I and MHCII molecules in TERM led to suggestion
      of tetraspanins' involvement in antigen presentation. In addition, certain
      tetraspanins function as viral co-receptors and may be important for viral egress
      from infected cells. It has recently become apparent that in addition to their
      purely structural function as organizers of TERM, tetraspanins also regulate
      various aspects of trafficking and biosynthetic processing of associated
      receptors. Here, we review recent studies, which specifically focus on this
      issue.

PMID- 17181774
TI  - A high-performance, small-scale microarray for expression profiling of many
      samples in Arabidopsis-pathogen studies.
AB  - Studies of the behavior of biological systems often require monitoring of the
      expression of many genes in a large number of samples. While whole-genome arrays
      provide high-quality gene-expression profiles, their high cost generally limits
      the number of samples that can be studied. Although inexpensive small-scale
      arrays representing genes of interest could be used for many applications, it is
      challenging to obtain accurate measurements with conventional small-scale
      microarrays. We have developed a small-scale microarray system that yields highly
      accurate and reproducible expression measurements. This was achieved by
      implementing a stable gene-based quantile normalization method for array-to-array
      normalization, and a probe-printing design that allows use of a statistical model
      to correct for effects of print tips and uneven hybridization. The array measures
      expression values in a single sample, rather than ratios between two samples.
      This allows accurate comparisons among many samples. The array typically yielded
      correlation coefficients higher than 0.99 between technically duplicated samples.
      Accuracy was demonstrated by a correlation coefficient of 0.88 between expression
      ratios determined from this array and an Affymetrix GeneChip, by quantitative RT
      PCR, and by spiking known amounts of specific RNAs into the RNA samples used for
      profiling. The array was used to compare the responses of wild-type, rps2 and
      ndr1 mutant plants to infection by a Pseudomonas syringae strain expressing
      avrRpt2. The results suggest that ndr1 affects a defense-signaling pathway(s) in
      addition to the RPS2-dependent pathway, and indicate that the microarray is a
      powerful tool for systems analyses of the Arabidopsis disease-signaling network.

PMID- 17181775
TI  - Spatial variation in H2O2 response of Arabidopsis thaliana root epidermal Ca2+
      flux and plasma membrane Ca2+ channels.
AB  - Hydrogen peroxide is an important regulatory agent in plants. This study
      demonstrates that exogenous H2O2 application to Arabidopsis thaliana root
      epidermis results in dose-dependent transient increases in net Ca2+ influx. The
      magnitude and duration of the transients were greater in the elongation zone than
      in the mature epidermis. In both regions, treatment with the cation channel
      blocker Gd3+ prevented H2O2-induced net Ca2+ influx, consistent with application
      of exogenous H2O2 resulting in the activation of plasma membrane Gd3+-sensitive
      Ca2+-influx pathways. Application of 10 mm H2O2 to the external plasma membrane
      face of elongation zone epidermal protoplasts resulted in the appearance of a
      hyperpolarization-activated Ca2+-permeable conductance. This conductance differed
      from that previously characterized as being responsive to extracellular hydroxyl
      radicals. In contrast, in mature epidermal protoplasts a plasma membrane
      hyperpolarization-activated Ca2+-permeable channel was activated only when H2O2
      was present at the intracellular membrane face. Channel open probability
      increased with intracellular [H2O2] and at hyperpolarized voltages. Unitary
      conductance decreased thus: Ba2+ > Ca2+ (14.5 pS) > Mg2+ > Zn2+ (20 mM external
      cation, 1 mM H2O2). Lanthanides and Zn2+ (but not TEA+) suppressed the open
      probability without affecting current amplitude. The results suggest spatial
      heterogeneity and differential sensitivity of Ca2+ channel activation by reactive
      oxygen species in the root that could underpin signalling.

PMID- 17181776
TI  - Genomic imprinting, methylation and molecular evolution of maize Enhancer of
      zeste (Mez) homologs.
AB  - Imprinted gene expression refers to differential transcription of alleles
      depending on their parental origin. To date, most examples of imprinted gene
      expression in plants occur in the triploid endosperm tissue. The Arabidopsis gene
      MEDEA displays an imprinted pattern of gene expression and has homology to the
      Drosophila Polycomb group (PcG) protein Enhancer-of-zeste (E(z)). We have tested
      the allele-specific expression patterns of the three maize E(z)-like genes Mez1,
      Mez2 and Mez3. The expression of Mez2 and Mez3 is not imprinted, with a bi
      allelic pattern of transcription for both genes in both the endosperm and
      embryonic tissue. In contrast, Mez1 displays a bi-allelic expression pattern in
      the embryonic tissue, and a mono-allelic expression pattern in the developing
      endosperm tissue. We demonstrate that mono-allelic expression of the maternal
      Mez1 allele occurs throughout endosperm development. We have identified a 556 bp
      differentially methylated region (DMR) located approximately 700 bp 5' of the
      Mez1 transcription start site. This region is heavily methylated at CpG and CpNpG
      nucleotides on the non-expressed paternal allele but has low levels of
      methylation on the expressed maternal allele. Molecular evolutionary analysis
      indicates that conserved domains of all three Mez genes are under purifying
      selection. The common imprinted expression of Mez1 and MEDEA, in concert with
      their likely evolutionary origins, suggests that there may be a requirement for
      imprinting of at least one E(z)-like gene in angiosperms.

PMID- 17181778
TI  - Subfunctionalization of PhyB1 and PhyB2 in the control of seedling and mature
      plant traits in maize.
AB  - Phytochromes are the primary red/far-red photoreceptors of higher plants,
      mediating numerous developmental processes throughout the life cycle, from
      germination to flowering. In seed plants, phytochromes are encoded by a small
      gene family with each member performing both distinct and redundant roles in
      mediating physiological responses to light cues. Studies in both eudicot and
      monocot species have defined a central role for phytochrome B in mediating
      responses to light in the control of several agronomically important traits,
      including plant height, transitions to flowering and axillary branch meristem
      development. Here we characterize Mutator-induced alleles of PhyB1 and a
      naturally occurring deletion allele of PhyB2 in Zea mays (maize). Using single
      and double mutants, we show that the highly similar PhyB1 and PhyB2 genes encode
      proteins with both overlapping and non-redundant functions that control seedling
      and mature plant traits. PHYB1 and PHYB2 regulate elongation of sheath and stem
      tissues of mature plants and contribute to the light-mediated regulation of PhyA
      and Cab gene transcripts. However, PHYB1 and not PHYB2 contributes significantly
      to the inhibition of mesocotyl elongation under red light, whereas PHYB2 and to a
      lesser extent PHYB1 mediate the photoperiod-dependent floral transition. This sub
      functionalization of PHYB activities in maize has probably occurred since the
      tetraploidization of maize, and may contribute to flowering time variation in
      modern-day varieties.

PMID- 17181779
TI  - Histidine kinases play important roles in the perception and signal transduction
      of hydrogen peroxide in the cyanobacterium, Synechocystis sp. PCC 6803.
AB  - Oxidative stress caused by reactive oxygen species and, in particular, to
      hydrogen peroxide (H(2)O(2)) has a major impact on all biological systems,
      including plants and microorganisms. We investigated the H(2)O(2)-inducible
      expression of genes in the cyanobacterium Synechocystis sp. PCC 6803 using genome
      wide DNA microarrays. Our systematic screening of a library of mutant lines with
      defects in histidine kinases (Hiks) by RNA slot-blot hybridization and DNA
      microarray analysis suggested that four Hiks, namely, Hik33, Hik34, Hik16 and
      Hik41, are involved in the perception and transduction of H(2)O(2) signals that
      regulate the gene expression of 26 of the 77 H(2)O(2)-inducible genes with
      induction factors higher than 4.0. Among the four Hiks, Hik33 was the main
      contributor and was responsible for 22 of the 26 H(2)O(2)-inducible genes under
      the control of the Hiks. By contrast to Hik33, PerR encoding putative peroxide
      sensing protein is involved in the regulation of only nine H(2)O(2)-inducible
      genes.

PMID- 17181777
TI  - Red colouration in apple fruit is due to the activity of the MYB transcription
      factor, MdMYB10.
AB  - Anthocyanin concentration is an important determinant of the colour of many
      fruits. In apple (Malus x domestica), centuries of breeding have produced
      numerous varieties in which levels of anthocyanin pigment vary widely and change
      in response to environmental and developmental stimuli. The apple fruit cortex is
      usually colourless, although germplasm does exist where the cortex is highly
      pigmented due to the accumulation of either anthocyanins or carotenoids. From
      studies in a diverse array of plant species, it is apparent that anthocyanin
      biosynthesis is controlled at the level of transcription. Here we report the
      transcript levels of the anthocyanin biosynthetic genes in a red-fleshed apple
      compared with a white-fleshed cultivar. We also describe an apple MYB
      transcription factor, MdMYB10, that is similar in sequence to known anthocyanin
      regulators in other species. We further show that this transcription factor can
      induce anthocyanin accumulation in both heterologous and homologous systems,
      generating pigmented patches in transient assays in tobacco leaves and highly
      pigmented apple plants following stable transformation with constitutively
      expressed MdMYB10. Efficient induction of anthocyanin biosynthesis in transient
      assays by MdMYB10 was dependent on the co-expression of two distinct bHLH
      proteins from apple, MdbHLH3 and MdbHLH33. The strong correlation between the
      expression of MdMYB10 and apple anthocyanin levels during fruit development
      suggests that this transcription factor is responsible for controlling
      anthocyanin biosynthesis in apple fruit; in the red-fleshed cultivar and in the
      skin of other varieties, there is an induction of MdMYB10 expression concurrent
      with colour formation during development. Characterization of MdMYB10 has
      implications for the development of new varieties through classical breeding or a
      biotechnological approach.

PMID- 17181780
TI  - The Lyme disease agent Borrelia burgdorferi requires BB0690, a Dps homologue, to
      persist within ticks.
AB  - Borrelia burgdorferi survives in an enzootic cycle, and Dps proteins protect DNA
      against damage during starvation or oxidative stress. The role of a Dps homologue
      encoded by Borrelia in spirochaete survival was assessed. Dps-deficient
      spirochaetes were infectious in mice via needle-inoculation at the dose of 10(5)
      spirochaetes. Larval ticks successfully acquired Dps-deficient spirochaetes via a
      blood meal on mice. However, after extended periods within unfed nymphs, the Dps
      deficient spirochaetes failed to be transmitted to a new host when nymphs fed.
      Our data suggest that Dps functions to protect the spirochaetes during dormancy
      in unfed ticks, and in its absence, the spirochaetes become susceptible during
      tick feeding. dps is differentially expressed in vivo- low in mice and high in
      ticks - but constitutively expressed in vitro, showing little change during
      growth or in response to oxidative stress. Borrelia Dps forms a dodecameric
      complex capable of sequestering iron. The Dps-deficient spirochaetes showed no
      defect in starvation and oxidative stress assays, perhaps due to the lack of iron
      in spirochaetes grown in vitro. Dps is critical for spirochaete persistence
      within ticks, and strategies to interfere with Dps could potentially reduce
      Borrelia populations in nature and thereby influence the incidence of Lyme
      disease.

PMID- 17181781
TI  - The small nucleoid protein Fis is involved in Vibrio cholerae quorum sensing.
AB  - Quorum sensing is a process of cell-cell communication that bacteria use to relay
      information to one another about the cell density and species composition of the
      bacterial community. Quorum sensing involves the production, secretion and
      population-wide detection of small signalling molecules called autoinducers. This
      process allows bacteria to synchronize group behaviours and act as multicellular
      units. The human pathogen, Vibrio cholerae, uses quorum sensing to co-ordinate
      such complex behaviours as pathogenicity and biofilm formation. The quorum
      sensing circuit of V. cholerae consists of two autoinducer/sensor systems, CAI
      1/CqsS and AI-2/LuxPQ, and the VarS/A-CsrA/BCD growth-phase regulatory system.
      Genetic analysis suggests that an additional regulatory arm involved in quorum
      sensing exists in V. cholerae. All of these systems channel information into the
      histidine phosphotransfer protein, LuxU, and/or the response regulator, LuxO.
      LuxO, when phosphorylated, activates the expression of four genes encoding the
      Qrr (quorum regulatory RNAs) small RNAs (sRNAs). The Qrr sRNAs destabilize the
      hapR transcript encoding the master regulator of quorum sensing, HapR. Here we
      identify the nucleoid protein Fis as playing a major role in the V. cholerae
      quorum-sensing circuit. Fis fulfils the predictions required to be the putative
      additional component that inputs information into the cascade: its expression is
      regulated in a growth phase-dependent manner; it requires LuxO but acts
      independently of LuxU, and it regulates all four qrr genes and, in turn, HapR by
      directly binding to the qrr gene promoters and modulating their expression.

PMID- 17181782
TI  - Antimicrobial peptides activate the Vibrio cholerae sigmaE regulon through an
      OmpU-dependent signalling pathway.
AB  - Vibrio cholerae, an enteric pathogen, is subject to assault by several membrane
      acting, host gut-derived antimicrobial peptides (AP). We previously found that a
      major V. cholerae outer membrane protein, OmpU, confers resistance to polymyxin B
      and to a bioactive peptide (P2) derived from the human bactericidal/permeability
      increasing protein. Here, we report that the alternative sigma factor sigma(E)
      also plays a critical role in determining V. cholerae resistance to AP and that
      OmpU and sigma(E) lie in the same pathway. In fact, we found that OmpU is a key
      determinant of basal sigma(E) expression. We also found that sublethal AP
      exposure activates sigma(E) and the sigma(E)-mediated periplasmic stress
      response. sigma(E) is not activated by P2 in V. cholerae cells lacking OmpU or
      DegS, a periplasmic protease that controls sigma(E) activity. The lack of AP
      elicited sigma(E) activation in a strain harbouring a point mutation in OmpU's
      putative DegS-binding residues provides support for a link between OmpU and DegS
      mediated activation of sigma(E). We propose that AP-induced membrane
      perturbations change the conformation of OmpU to trigger a DegS-dependent
      sigma(E)-activating cascade. Thus, OmpU appears to act as a sensor component in a
      signal transduction pathway.

PMID- 17181783
TI  - Regulation of tylosin production: role of a TylP-interactive ligand.
AB  - Gamma-butyrolactones regulate secondary metabolism and, sometimes, sporulation in
      actinomycetes by binding to specific receptor proteins, causing their
      dissociation from DNA targets and releasing the latter from transcriptional
      repression. Previously, in engineered strains of Streptomyces lividans, we showed
      that TylP, a deduced gamma-butyrolactone receptor, downregulated reporter gene
      expression driven by tylP, tylQ or tylS promoter DNA. These genes all control
      tylosin production in Streptomyces fradiae. Thus, at early stages of
      fermentation, TylQ represses tylR whereas TylS is needed for transcriptional
      activation of tylR. Importantly, TylR is the key activator of tylosin
      biosynthetic genes. Here, we show that HIS-tagged TylP binds to specific DNA
      sequences, similar to the targets for authentic gamma-butyrolactone receptors, in
      the promoters of tylP, tylQ and tylS. Moreover, such binding is disrupted by
      material produced in S. fradiae and extractable by organic solvent. That putative
      gamma-butyrolactone material was not produced when orf18 * was disrupted within
      the S. fradiae genome and only about 1% of that activity survived inactivation of
      orf16 *, suggesting roles for the respective gene products in gamma-butyrolactone
      synthesis. Continued synthesis of tylosin by the disrupted strains contrasts with
      other reports that loss of gamma-butyrolactones abolishes antibiotic production.

PMID- 17181784
TI  - Interplay between primase and replication factor C in the hyperthermophilic
      archaeon Sulfolobus solfataricus.
AB  - The heterodimeric primase from the hyperthermophilic archaeon Sulfolobus
      solfataricus synthesizes long RNA and DNA products in vitro. How primer synthesis
      by primase is coupled to primer extension by DNA polymerase in this organism is
      unclear. Here we show that the small subunit of the clamp loader replication
      factor C (RFC) of S. solfataricus interacted with both the catalytic and non
      catalytic subunits of the primase by yeast two-hybrid and co-immunoprecipitation
      assays. Further, the primase-RFC interaction was also identified in the cell
      extract of S. solfataricus. Deletion analysis indicated that the small subunit of
      RFC interacted strongly with the N-terminal domain of the catalytic subunit of
      the primase. RFC stimulated dinucleotide formation but decreased the amount of
      primers synthesized by the primase. The inhibition of primer synthesis is
      consistent with the observation that RFC reduced the affinity of the primase for
      DNA templates. On the other hand, primase stimulated the ATPase activity of RFC.
      These findings suggest that the primase-RFC interaction modulates the activities
      of both enzymes and therefore may be involved in the regulation of primer
      synthesis and the transfer of primers to DNA polymerase in Archaea.

PMID- 17181785
TI  - A novel protein kinase family in Plasmodium falciparum is differentially
      transcribed and secreted to various cellular compartments of the host cell.
AB  - Processes at the surface of Plasmodium falciparum-infected erythrocytes such as
      antigenic variation and cytoadhesion may be modulated by active signalling
      between host and parasite. Potential candidates for this role include the
      putative kinases of the FIKK family. The novel Apicomplexa-specific FIKK gene has
      expanded in P. falciparum to 20 sequence-related members distributed between 11
      chromosomes. Specific antibodies raised against different members indicated that
      most FIKK proteins locate to punctate foci in the erythrocyte cytoplasm that
      colocalized with Maurer's clefts proteins. One FIKK member dissociates at the
      trophozoite stage from the Maurer's clefts and relocates with the erythrocyte
      cytoskeleton. Another FIKK protein, despite having a PEXEL motif, remains located
      within the parasite. FIKK proteins possess the essential residues for
      phosphotransferase activity. We show that protein kinase activity was detected in
      immunoprecipitates obtained with two anti-FIKK antibodies. Quantitative PCR
      analysis revealed differential gene transcription of the FIKK paralogues in
      asexual blood stages parasites. We observed significant changes in the
      transcription pattern between parasites with different adhesion phenotypes. Our
      data suggest a role of FIKK proteins in the remodelling of the erythrocyte
      surface and reveal the existence of an adaptable parasite system able to sense
      intra- and possibly extracellular changes.

PMID- 17181786
TI  - If Rome is burning, why are we fiddling?

PMID- 17181787
TI  - Who needs to spend money on conservation science anyway?

PMID- 17181789
TI  - The trial.

PMID- 17181790
TI  - Real coda to an imaginary trial.

PMID- 17181791
TI  - Disenchanting the rhetoric: human uniqueness and human responsibility.

PMID- 17181792
TI  - Preparing students for conservation careers through project-based learning.

PMID- 17181793
TI  - Taxonomic considerations in listing subspecies under the U.S. Endangered Species
      Act.
AB  - The U.S. Endangered Species Act (ESA) allows listing of subspecies and other
      groupings below the rank of species. This provides the U.S. Fish and Wildlife
      Service and the National Marine Fisheries Service with a means to target the most
      critical unit in need of conservation. Although roughly one-quarter of listed
      taxa are subspecies, these management agencies are hindered by uncertainties
      about taxonomic standards during listing or delisting activities. In a review of
      taxonomic publications and societies, we found few subspecies lists and none that
      stated standardized criteria for determining subspecific taxa. Lack of criteria
      is attributed to a centuries-old debate over species and subspecies concepts.
      Nevertheless, the critical need to resolve this debate for ESA listings led us to
      propose that minimal biological criteria to define disjunct subspecies (legally
      or taxonomically) should include the discreteness and significance criteria of
      distinct population segments (as defined under the ESA). Our subspecies criteria
      are in stark contrast to that proposed by supporters of the phylogenetic species
      concept and provide a clear distinction between species and subspecies. Efforts
      to eliminate or reduce ambiguity associated with subspecies-level classifications
      will assist with ESA listing decisions. Thus, we urge professional taxonomic
      societies to publish and periodically update peer-reviewed species and subspecies
      lists. This effort must be paralleled throughout the world for efficient
      taxonomic conservation to take place.

PMID- 17181794
TI  - Globalization of the Amazon soy and beef industries: opportunities for
      conservation.
AB  - Amazon beef and soybean industries, the primary drivers of Amazon deforestation,
      are increasingly responsive to economic signals emanating from around the world,
      such as those associated with bovine spongiform encephalopathy (BSE, "mad cow
      disease") outbreaks and China's economic growth. The expanding role of these
      economic "teleconnections" (coupled phenomena that take place in distant places
      on the planet) led to a 3-year period (2002-2004) of historically high
      deforestation rates. But it also increases the potential for large-scale
      conservation in the region as markets and finance institutions demand better
      environmental and social performance of beef and soy producers. Cattle ranchers
      and soy farmers who have generally opposed ambitious government regulations that
      require forest reserves on private property are realizing that good land
      stewardship-including compliance with legislation-may increase their access to
      expanding domestic and international markets and to credit and lower the risk of
      "losing" their land to agrarian reform. The realization of this potential depends
      on the successful negotiation of social and environmental performance criteria
      and an associated system of certification that are acceptable to both the
      industries and civil society. The foot-and-mouth eradication system, in which
      geographic zones win permission to export beef, may provide an important model
      for the design of a low-cost, peer-enforced, socioenvironmental certification
      system that becomes the mechanism by which beef and soy industries gain access to
      markets outside the Amazon.

PMID- 17181795
TI  - Shrinking tropical forests, human agents of change, and conservation policy.
AB  - Human agents of landscape transformation in the tropics affect forests
      differently as the forests decline in size. Five agents of change--road builders,
      corporate concession holders, community forest managers, park advocates, and
      urban consumers--have different effects on large forests in remote tropical
      regions than they do on remnant forests in settled agricultural regions. Because
      forests vary so much in size across tropical regions, these differences in the
      effects of agents on forests have important implications for regional
      conservation efforts. To make these implications explicit, I compared the effects
      of the five agents in regions with large forests with their effects in regions
      with small forests. The comparisons indicated that, as forests declined in size,
      new roads no longer destroyed forests, corporate loggers left the forests,
      community forest managers became more effective, parks became less feasible as a
      means of conservation, and urban consumers initiated tree planting. My results
      suggest that awareness about the changing effects of humans on landscapes with
      shrinking forests can serve as a useful tool in formulating regionally
      appropriate policies for conserving tropical forests.

PMID- 17181796
TI  - Patch mosaic burning for biodiversity conservation: a critique of the
      pyrodiversity paradigm.
AB  - Fire management is increasingly focusing on introducing heterogeneity in burning
      patterns under the assumption that "pyrodiversity begets biodiversity." This
      concept has been formalized as patch mosaic burning (PMB), in which fire is
      manipulated to create a mosaic of patches representative of a range of fire
      histories to generate heterogeneity across space and time. Although PMB is an
      intuitively appealing concept, it has received little critical analysis. Thus we
      examined ecosystems where PMB has received the most attention and has been the
      most extensively implemented: tropical and subtropical savannas of Australia and
      Africa. We identified serious shortcomings of PMB: the ecological significance of
      different burning patterns remains unknown and details of desired fire mosaics
      remain unspecified. This has led to fire-management plans based on pyrodiversity
      rhetoric that lacks substance in terms of operational guidelines and capacity for
      meaningful evaluation. We also suggest that not all fire patterns are
      ecologically meaningful: this seems particularly true for the highly fire-prone
      savannas of Australia and South Africa. We argue that biodiversity-needs
      pyrodiversity advocacy needs to be replaced with a more critical consideration of
      the levels of pyrodiversity needed for biodiversity and greater attention to
      operational guidelines for its implementation.

PMID- 17181797
TI  - Conservation biology, genetically modified organisms, and the biosafety protocol.
AB  - Concerns have been raised regarding the potential adverse effects on biological
      diversity of the use of living modified organisms (LMOs, which are commonly known
      by similar terms such as genetically modified organisms). At the international
      level these concerns are addressed in part by an agreement known as the Cartagena
      Protocol on Biosafety and include potential toxic effects of insect-resistant
      crops on nontarget organisms and potential ecological effects of gene flow from
      modified crops, fish, microorganisms, or insects to wild species or counterparts.
      We reviewed the protocol's main provisions, including those dealing with risk
      assessment and risk management, decision making on imports, documentation
      accompanying shipments, and liability resulting from damages caused by LMOs. A
      medium-term program of work has been adopted by the parties, which includes the
      potential contribution of conservation biologists to delivering capacity
      building, developing risk assessment guidance, evaluating mechanisms of potential
      ecological damages from LMOs, and other issues. Conservation biologists and other
      experts have opportunities to influence the negotiations and implementation of
      the protocol by providing inputs at meetings, offering expertise to governments
      and organizations, and participating in or developing relevant projects and
      initiatives. Involvement of conservation biologists in the implementation and
      further development of the protocol would contribute to its effectiveness.

PMID- 17181798
TI  - Measurement and meaningfulness in conservation science.
AB  - Incomplete databases often require conservation scientists to estimate data
      either through expert judgment or other scoring, rating, and ranking procedures.
      At the same time, ecosystem complexity has led to the use of increasingly
      sophisticated algorithms and mathematical models to aid in conservation
      theorizing, planning, and decision making. Understanding the limitations imposed
      by the scales of measurement of conservation data is important for the
      development of sound conservation theory and policy. In particular, biodiversity
      valuation methods, systematic conservation planning algorithms, geographic
      information systems (GIS), and other conservation metrics and decision-support
      tools, when improperly applied to estimated data, may lead to conclusions based
      on numerical artifact rather than empirical evidence. The representational theory
      of measurement is described here, and the description includes definitions of the
      key concepts of scale, scale type, and meaningfulness. Representational
      measurement is the view that measurement entails the faithful assignment of
      numbers to empirical entities. These assignments form scales that are organized
      into a hierarchy of scale types. A statement involving scales is meaningful if
      its truth value is invariant under changes of scale within scale type. I apply
      these concepts to three examples of measurement practice in the conservation
      literature. The results of my analysis suggest that conservation scientists do
      not always investigate the scale type of estimated data and hence may derive
      results that are not meaningful. Recognizing the complexity of observation and
      measurement in conservation biology, and the constraints that measurement theory
      imposes, the examples are accompanied by suggestions for informal estimation of
      the scale type of conservation data and for conducting meaningful analysis and
      synthesis of this information.

PMID- 17181799
TI  - A global indicator for biological invasion.
AB  - "Trends in invasive alien species" is one of only two indicators of threat to
      biodiversity that form part of the Convention on Biological Diversity's (CBD)
      framework for monitoring progress toward its "2010 target" (i.e., the commitment
      to achieve by 2010 a significant reduction in the current rate of biodiversity
      loss). To date, however, there is no fully developed indicator for invasive alien
      species (IAS) that combines trends, derived from a standard set of methods,
      across species groups, ecosystems, and regions. Here we provide a rationale for
      the form and characteristics of an indicator of trends in IAS that will meet the
      2010 framework goal and targets for this indicator. We suggest single and
      composite indicators that include problem-status and management-status measures
      that are designed to be flexible, readily disaggregated, and as far as possible
      draw on existing data. The single indicators at national and global scales are
      number of IAS and numbers of operational management plans for IAS. Global trends
      in IAS are measured as the progress of nations toward the targets of stabilizing
      IAS numbers and the implementation of IAS management plans. The proposed global
      indicator thus represents a minimum information set that most directly addresses
      the indicator objective and simultaneously aims to maximize national
      participation. This global indicator now requires testing to assess its accuracy,
      sensitivity, and tractability. Although it may not be possible to achieve the
      desired objective for a global indicator of biological invasion by 2010 as
      comprehensively as desired, it seems possible to obtain trend estimates for a
      component of the taxa, ecosystems, and regions involved. Importantly, current
      indicator development initiatives will also contribute to developing the
      mechanisms necessary for monitoring global trends in IAS beyond 2010.

PMID- 17181800
TI  - Guidelines for systematic review in conservation and environmental management.
AB  - An increasing number of applied disciplines are utilizing evidence-based
      frameworks to review and disseminate the effectiveness of management and policy
      interventions. The rationale is that increased accessibility of the best
      available evidence will provide a more efficient and less biased platform for
      decision making. We argue that there are significant benefits for conservation in
      using such a framework, but the scientific community needs to undertake and
      disseminate more systematic reviews before the full benefit can be realized. We
      devised a set of guidelines for undertaking formalized systematic review, based
      on a health services model. The guideline stages include planning and conducting
      a review, including protocol formation, search strategy, data inclusion, data
      extraction, and analysis. Review dissemination is addressed in terms of current
      developments and future plans for a Web-based open-access library. By the use of
      case studies we highlight critical modifications to guidelines for protocol
      formulation, data-quality assessment, data extraction, and data synthesis for
      conservation and environmental management. Ecological data presented significant
      but soluble challenges for the systematic review process, particularly in terms
      of the quantity, accessibility, and diverse quality of available data. In the
      field of conservation and environmental management there needs to be further
      engagement of scientists and practitioners to develop and take ownership of an
      evidence-based framework.

PMID- 17181801
TI  - Assessing the effectiveness of reserve acquisition programs in protecting rare
      and threatened species.
AB  - Measuring the effectiveness of reserve networks is essential to ensure that
      conservation objectives such as species persistence are being met. We devised a
      new approach for measuring the effectiveness of land conservation in protecting
      rare and threatened species and applied it to an ecosystem of global
      significance. We compiled detailed global distributional data for 36 rare and
      threatened plants and animals found in the Lake Wales Ridge ecosystem in central
      Florida (U.S.A.). For each species, we developed a set of protection indices
      based in part on criteria used to categorize species for the World Conservation
      Union's Red List. We calculated protection indexes under three different
      conservation scenarios: a past scenario, which assumed recent, major land
      acquisition efforts never occurred; a current scenario, which assumed no
      additional areas are saved beyond what is currently protected; and a targeted
      scenario, which assumed all of the remaining areas targeted for protection are
      eventually acquired. This approach enabled us to quantify the progress, in terms
      of reduced risk of extinction, that conservationists have made in protecting
      target species. It also revealed the limited success these land-acquisition
      efforts have had in reducing those extinction risks associated with loss of
      habitat or small geographic ranges. Many species of the Lake Wales Ridge will
      remain at high risk of extinction even if planned land-acquisition efforts are
      completely successful. By calculating protection indexes with and without each
      site for all imperiled species, we also quantified the contribution of each
      protected area to the conservation of each species, enabling local conservation
      decisions to be made in the context of a larger (global) perspective. The
      protection index approach can be adapted readily to other ecosystems with
      multiple rare and threatened species.

PMID- 17181802
TI  - Incorporating evolutionary measures into conservation prioritization.
AB  - Conservation prioritization is dominated by the threat status of candidate
      species. However, species differ markedly in the shared genetic information they
      embody, and this information is not taken into account if species are prioritized
      by threat status alone. We developed a system of prioritization that incorporates
      both threat status and genetic information and applied it to 9546 species of
      birds worldwide. We devised a simple measure of a species' genetic value that
      takes into account the shape of the entire taxonomic tree of birds. This measure
      approximates the evolutionary history that each species embodies and sums to the
      phylogenetic diversity of the entire taxonomic tree. We then combined this
      genetic value with each species' probability of extinction to create a species
      specific measure of expected loss of genetic information. The application of our
      methods to the world's avifauna showed that ranking species by expected loss of
      genetic information may help preserve bird evolutionary history by upgrading
      those threatened species with fewer close relatives. We recommend developing a
      mechanism to incorporate a species' genetic value into the prioritization
      framework.

PMID- 17181803
TI  - Presence-absence versus abundance data for monitoring threatened species.
AB  - Effective detection of population trend is crucial for managing threatened
      species. Little theory exists, however, to assist managers in choosing the most
      cost-effective monitoring techniques for diagnosing trend. We present a framework
      for determining the optimal monitoring strategy by simulating a manager
      collecting data on a declining species, the Chestnut-rumped Hylacola (Hylacola
      pyrrhopygia parkeri), to determine whether the species should be listed under the
      IUCN (World Conservation Union) Red List. We compared the efficiencies of two
      strategies for detecting trend, abundance, and presence-absence surveys, under
      financial constraints. One might expect the abundance surveys to be superior
      under all circumstances because more information is collected at each site.
      Nevertheless, the presence-absence data can be collected at more sites because
      the surveyor is not obliged to spend a fixed amount of time at each site. The
      optimal strategy for monitoring was very dependent on the budget available. Under
      some circumstances, presence-absence surveys outperformed abundance surveys for
      diagnosing the IUCN Red List categories cost-effectively. Abundance surveys were
      best if the species was expected to be recorded more than 16 times/year;
      otherwise, presence-absence surveys were best. The relationship between the
      strategies we investigated is likely to be relevant for many comparisons of
      presence-absence or abundance data. Managers of any cryptic or low-density
      species who hope to maximize their success of estimating trend should find an
      application for our results.

PMID- 17181804
TI  - Uncertainty analysis for regional-scale reserve selection.
AB  - Methods for reserve selection and conservation planning often ignore uncertainty.
      For example, presence-absence observations and predictions of habitat models are
      used as inputs but commonly assumed to be without error. We applied information
      gap decision theory to develop uncertainty analysis methods for reserve
      selection. Our proposed method seeks a solution that is robust in achieving a
      given conservation target, despite uncertainty in the data. We maximized
      robustness in reserve selection through a novel method, "distribution
      discounting," in which the site- and species-specific measure of conservation
      value (related to species-specific occupancy probabilities) was penalized by an
      error measure (in our study, related to accuracy of statistical prediction).
      Because distribution discounting can be implemented as a modification of input
      files, it is a computationally efficient solution for implementing uncertainty
      analysis into reserve selection. Thus, the method is particularly useful for high
      dimensional decision problems characteristic of regional conservation assessment.
      We implemented distribution discounting in the zonation reserve-selection
      algorithm that produces a hierarchy of conservation priorities throughout the
      landscape. We applied it to reserve selection for seven priority fauna in a
      landscape in New South Wales, Australia. The distribution discounting method can
      be easily adapted for use with different kinds of data (e.g., probability of
      occurrence or abundance) and different landscape descriptions (grid or patch
      based) and incorporated into other reserve-selection algorithms and software.

PMID- 17181805
TI  - Resilience of southwestern Amazon forests to anthropogenic edge effects.
AB  - Anthropogenic edge effects can compromise the conservation value of mature
      tropical forests. To date most edge-effect research in Amazonia has concentrated
      on forests in relatively seasonal locations or with poor soils in the east of the
      basin. We present the first evaluation from the relatively richer soils of far
      western Amazonia on the extent to which mature forest biomass, diversity, and
      composition are affected by edges. In a southwestern Amazonian landscape we
      surveyed woody plant diversity, species composition, and biomass in 88x0.1 ha
      samples of unflooded forest that spanned a wide range in soil properties and
      included samples as close as 50 m and as distant as >10 km from anthropogenic
      edges. We applied Mantel tests, multiple regression on distance matrices, and
      other multivariate techniques to identify anthropogenic effects before and after
      accounting for soil factors and spatial autocorrelation. The distance to the
      nearest edge, access point, and the geographical center of the nearest community
      ("anthropogenic-distance effects") all had no detectable effect on tree biomass
      or species diversity. Anthropogenic-distance effects on tree species composition
      were also below the limits of detection and were negligible in comparison with
      natural environmental and spatial factors. Analysis of the data set's capacity to
      detect anthropogenic effects confirmed that the forests were not severely
      affected by edges, although because our study had few plots within 100 m of
      forest edges, our confidence in patterns in the immediate vicinity of edges is
      limited. It therefore appears that the conservation value of most "edge" forests
      in this region has not yet been compromised substantially. We caution that
      because this is one case study it should not be overinterpreted, but one
      explanation for our findings may be that western Amazonian tree species are
      naturally faster growing and more disturbance adapted than those farther east.

PMID- 17181806
TI  - Fire and green-tree retention in conservation of red-listed and rare deadwood
      dependent beetles in Finnish boreal forests.
AB  - Habitat loss, fragmentation, and declining habitat quality have created an
      extinction debt in boreal forests, which could be partly reversed by deliberately
      improving the habitat quality in managed areas outside reserves. We studied the
      effects of green-tree retention and controlled burning on red-listed and rare,
      deadwood-dependent (saproxylic) beetles in a large-scale field experiment in
      eastern Finland. Our factorial study design included 24 sites dominated by Scots
      pine (Pinus sylvestris L.) and with three levels of green-tree retention (0, 10,
      and 50 m3/ha) and uncut controls. Twelve of the 24 sites were burned in 2001. We
      sampled beetles with 10 flight-intercept traps on each site during the years 2000
      2002 (i.e., 1 pretreatment and 2 post-treatment years). A total sample of 153,449
      individuals representing 1,160 beetle species yielded 2,107 specimens of 84 red
      listed or rare saproxylic species. The richness of these species was higher on
      the burned than on the unburned sites, and higher levels of green-tree retention
      promoted species richness, but there were clear differences between the years.
      The richness of red-listed and rare saproxylic species increased in the first
      post-treatment year, evidently due to the treatments, continued to increase on
      the burned sites in the second post-treatment year, but decreased on the unburned
      sites. Our results showed that the living conditions of many red-listed and rare
      saproxylic species could be improved significantly with rather simple alterations
      to forest management methods. Controlled burning with high levels of green-tree
      retention creates resources for many saproxylic species, but increasing the
      levels of green-tree retention in unburned areas can also be beneficial.

PMID- 17181807
TI  - Spillover of agriculturally subsidized predators as a potential threat to native
      insect herbivores in fragmented landscapes.
AB  - Habitat loss and fragmentation can have strong negative impacts on populations of
      some native species. Spillover of generalist natural enemies from the surrounding
      landscape matrix is one mechanism potentially generating such effects, yet this
      has been rarely studied in insects. We examined the influence of habitat
      conversion to agriculture on the abundance and potential effects of predatory
      coccinellid beetles on native insect herbivores within 12 grassland remnants in
      central Nebraska (U.S.A.). Results of sweep sampling revealed that coccinellids
      were three to six times more abundant at native grassland sites embedded within
      cropland-dominated landscapes compared with control sites in grassland-dominated
      landscapes over the 3 years of the study. Exclusion experiments further
      demonstrated that predation intensity was strongly related to coccinellid
      abundances across sites and that coccinellids can dramatically reduce densities
      of a native aphid herbivore. In contrast to studies of specialized insect
      parasitoids, which have generally found reduced enemy pressure in fragmented
      landscapes, our results suggest that native herbivores may in some cases
      experience increased consumer pressure in landscapes with increasing habitat loss
      because of spillover of generalist predators from surrounding cropland habitats.

PMID- 17181808
TI  - Using ecological-niche modeling as a conservation tool for freshwater species:
      live-bearing fishes in central Mexico.
AB  - Ecological-niche modeling is an important tool for conservation assessment of
      terrestrial species; however, its applicability has been poorly explored in the
      aquatic realm. Goodeines are a monophyletic group of viviparous freshwater fishes
      that are well known in central Mexico, with 41 species in 19 genera. Given the
      number of threats to biodiversity in the region, goodeines represent an excellent
      model with which to test novel conservation approaches. We assessed the
      conservation status of the goodeines (37 species), based on their potential
      distributions predicted by ecological-niche models generated with the genetic
      algorithm for rule-set prediction (GARP). Predictions of species' distributions
      performed well in six out of eight species for which sufficient information was
      available to perform estimations of the area under the curve (AUC) in receiver
      operating characteristic plots. Extensive field surveys conducted in recent years
      in most cases confirm the models' predictions. Species richness exhibited a
      nested pattern, in which the number of species increased toward the center of the
      distribution of the group. At the basin level, the Rio Ameca Basin had the
      highest number of species (11), chiefly because of the high number of
      microendemic species (6). Human activities within water bodies (e.g., extensive
      aquaculture) and drainages (e.g., agriculture, ranching, industrial activities)
      have affected most goodeines severely, given the deleterious effects of pollution
      and introductions of exotic species, such as carp (Cyprinus carpio,
      Ctenopharingodon idella) and tilapia (Oreochromis spp.). Our results paint a
      pessimistic picture for the long-term survival of many goodeines in their natural
      environment, and realistic conservation measures are complex and would require
      immediate protection of specific areas that we have identified. Ecological-niche
      modeling is a suitable tool for conservation assessment of freshwater species,
      but availability of environmental information on aquatic systems (e.g.,
      temperature, water speed, pH, oxygen concentration) would improve distributional
      predictions.

PMID- 17181809
TI  - Forecasting the spread of invasive rainbow smelt in the Laurentian Great Lakes
      region of North America.
AB  - Rainbow smelt (Osmerus mordax) have invaded many North American lakes, often
      resulting in the extirpation of native fish populations. Yet, their invasion is
      incipient and provides the rationale for identifying ecosystems likely to be
      invaded and where management and prevention efforts should be focused. To predict
      smelt presence and absence, we constructed a classification-tree model based on
      habitat data from 354 lakes in the native range for smelt in southern Maine.
      Maximum lake depth, lake area, and Secchi depth (surrogate measure of lake
      productivity) were the most important predictors. We then used our model to
      identify lakes vulnerable to invasion in three regions outside the smelt's native
      range: northern Maine (52 of 244 lakes in the non-native range), Ontario (4447 of
      8110), and Wisconsin (553 of 5164). We further identified a subset of lakes with
      a strong potential for impact (potential-impact lakes) based on the presence of
      fish species that are affected by rainbow smelt. Ninety-four percent of
      vulnerable lakes in the non-native range in Maine are also potential-impact
      lakes, as are 94% and 58% of Ontario and Wisconsin's vulnerable lakes,
      respectively. Our modeling approach can be applied to other invaders and regions
      to identify invasion-prone ecosystems, thus aiding in the management of invasive
      species and the efficient allocation of invasive species mitigation and
      prevention resources.

PMID- 17181810
TI  - Influence of forest fragmentation on community structure of frogs and lizards in
      northeastern Costa Rica.
AB  - To better understand responses of reptiles and amphibians to forest fragmentation
      in the lowland Neotropics, we examined community and population structure of
      frogs and lizards in the fragmented landscape surrounding La Selva Biological
      Station in the Sarapiqui region of northeastern Costa Rica. We used diurnal
      quadrats and nocturnal transects to sample frogs and lizards in nine forest
      fragments (1-7 ha each) and La Selva (1100 ha). Species richness in all fragments
      combined was 85% of that found in La Selva with comparable sampling effort.
      Richness varied from 10 to 24 species among forest fragments, compared with 36
      species at La Selva. Lizard density was higher and frog density was lower in
      forest fragments than in La Selva. Community composition varied among sites and
      by fragment size class, and species occurrence was nested with respect to
      fragment area. Isolation and habitat variables did not significantly affect
      species richness, composition, or nestedness. We classified 34% of species as
      fragmentation sensitive because they were absent or occurred at low densities in
      fragments. Nevertheless, the relatively high diversity observed in the entire set
      of fragments indicates that preserving a network of small forest patches may be
      of considerable conservation value to the amphibians and reptiles of this region.

PMID- 17181811
TI  - Demographic characteristics of extinction in a small, insular population of house
      sparrows in northern Norway.
AB  - In conservation ecology there is an urgent need for indicators that can be used
      to predict the risk of extinction of populations. Identifying extinction-prone
      populations has been difficult because few data sets on the demographic
      characteristics of the final stage to extinction are available and because of
      problems in separating out stochastic effects from changes in the expected
      dynamics. We documented the demographic changes that occurred during the period
      prior to extinction of a small island population of House Sparrows (Passer
      domesticus) after the end of permanent human settlement. A mark-recapture
      analysis revealed that this decline to extinction was mainly due to increased
      mortality after closure of the last farm that resulted in a negative long-term
      specific growth rate. No change occurred in either the structural composition
      (breeding sex ratio and age distribution) of the population or in female
      recruitment. No male, however, recruits were produced on the island after the
      farm closure. Based on a simple, stochastic, density-dependent model we
      constructed a population prediction interval (PPI) to estimate the time to
      extinction. The 95% PPI slightly overestimated the time to extinction with large
      uncertainty in predictions, especially due to the influence of demographic
      stochasticity and parameter drift. Our results strongly emphasize the importance
      of access to data on temporal variation that can be used to parameterize simple
      population models that allow estimation of critical parameters for credible
      prediction of time to extinction.

PMID- 17181813
TI  - Effect of family support on the success of translocated black-tailed prairie
      dogs.
AB  - Translocation has become a widely used conservation tool but remains only
      marginally successful. High mortality is often attributed to predation, but for
      highly social species, founder group composition may also play a critical role in
      postrelease survival. I compared the fitness of black-tailed prairie dogs
      translocated with or without their family groups. Animals in the family
      translocated groups were individually marked and observed until coterie
      membership was determined. Nonfamily translocated animals were trapped without
      regard to family membership. I measured fitness by retrapping all marked animals
      remaining at release sites in the summer following release. Family translocated
      animals were five times more likely to survive and had significantly higher
      reproductive success than those translocated without families. Predation was an
      important impediment of translocation success, but family translocation
      significantly reduced the success of predators on newly established prairie dog
      colonies. Postrelease survival was also affected by the timing of release, but
      appeared to be more important for juveniles than adults. These results
      demonstrate the importance of considering familiarity when translocations are
      required. More broadly, these results illustrate the value of applying animal
      behavior to conservation efforts and suggest that other species dependent on
      social interactions for survival and reproduction may benefit substantially from
      the maintenance of social groups during translocations.

PMID- 17181812
TI  - Prioritization for conservation of northern European cattle breeds based on
      analysis of microsatellite data.
AB  - Northern European indigenous cattle breeds are currently endangered and at a risk
      of becoming extinct. We analyzed variation at 20 microsatellite loci in 23
      indigenous, 3 old imported, and 9 modern commercial cattle breeds that are
      presently distributed in northern Europe. We measured the breeds' allelic
      richness and heterozygosity, and studied their genetic relationships with a
      neighbor-joining tree based on the Chord genetic distance matrix. We used the
      Weitzman approach and the core set diversity measure of Eding et al. (2002) to
      quantify the contribution of each breed to the maximum amount of genetic
      diversity and to identify breeds important for the conservation of genetic
      diversity. We defined 11 breeds as a "safe set" of breeds (not endangered) and
      estimated a reduction in genetic diversity if all nonsafe (endangered) breeds
      were lost. We then calculated the increase in genetic diversity by adding one by
      one each of the nonsafe breeds to the safe set (the safe-set-plus-one approach).
      The neighbor-joining tree grouped the northern European cattle breeds into Black
      and-White type, Baltic Red, and Nordic cattle groups. Vane cattle, Bohus Poll,
      and Danish Jersey had the highest relative contribution to the maximum amount of
      genetic diversity when the diversity was quantified by the Weitzman diversity
      measure. These breeds not only showed phylogenetic distinctiveness but also low
      within-population variation. When the Eding et al. method was applied, Eastern
      Finncattle and Lithuanian White Backed cattle contributed most of the genetic
      variation. If the loss of the nonsafe set of breeds happens, the reduction in
      genetic diversity would be substantial (72%) based on the Weitzman approach, but
      relatively small (1.81%) based on the Eding et al. method. The safe set contained
      only 66% of the observed microsatellite alleles. The safe-set-plus-one approach
      indicated that Bohus Poll and Vane cattle contributed most to the Weitzman
      diversity, whereas the Eastern Finncattle contribution was the highest according
      to the Eding et al. method. Our results indicate that both methods of Weitzman
      and Eding et al. recognize the importance of local populations as a valuable
      resource of genetic variation.

PMID- 17181814
TI  - Decline in relative abundance of bottlenose dolphins exposed to long-term
      disturbance.
AB  - Studies evaluating effects of human activity on wildlife typically emphasize
      short-term behavioral responses from which it is difficult to infer biological
      significance or formulate plans to mitigate harmful impacts. Based on decades of
      detailed behavioral records, we evaluated long-term impacts of vessel activity on
      bottlenose dolphins (Tursiops sp.) in Shark Bay, Australia. We compared dolphin
      abundance within adjacent 36-km2 tourism and control sites, over three
      consecutive 4.5-year periods wherein research activity was relatively constant
      but tourism levels increased from zero, to one, to two dolphin-watching
      operators. A nonlinear logistic model demonstrated that there was no difference
      in dolphin abundance between periods with no tourism and periods in which one
      operator offered tours. As the number of tour operators increased to two, there
      was a significant average decline in dolphin abundance (14.9%; 95% CI=-20.8 to 
      8.23), approximating a decline of one per seven individuals. Concurrently, within
      the control site, the average increase in dolphin abundance was not significant
      (8.5%; 95% CI=-4.0 to +16.7). Given the substantially greater presence and
      proximity of tour vessels to dolphins relative to research vessels, tour-vessel
      activity contributed more to declining dolphin numbers within the tourism site
      than research vessels. Although this trend may not jeopardize the large,
      genetically diverse dolphin population of Shark Bay, the decline is unlikely to
      be sustainable for local dolphin tourism. A similar decline would be devastating
      for small, closed, resident, or endangered cetacean populations. The substantial
      effect of tour vessels on dolphin abundance in a region of low-level tourism
      calls into question the presumption that dolphin-watching tourism is benign.

PMID- 17181815
TI  - Deforestation and plant diversity of Madagascar's littoral forests.
AB  - Few studies have attempted to quantify the reduction or document the floristic
      composition of forests in Madagascar. Thus, we focused specifically on
      deforestation and plant diversity in Madagascar's eastern littoral community. We
      used a data set of approximately 13,500 specimen records compiled from both
      historical and contemporary collections resulting from recent intensive inventory
      efforts to enumerate total plant species richness and to analyze the degree of
      endemism within littoral forests. Change in littoral forest cover from original
      to current extent was estimated using geographical information systems tools,
      remote sensing data (satellite imagery and low-elevation digital photography),
      and environmental data layers. Of the original littoral forest only 10.3% remains
      in the form of small forest parcels, and only 1.5% of these remaining fragments
      are included within the existing protected-areas network. Additionally,
      approximately 13% of Madagascar's total native flora has been recorded from these
      forests that originally occupied <1% of its total land surface, and over 25% of
      the 1535 plant species known from littoral forests are endemic to this community.
      Given the ongoing pressure from human settlement along Madagascar's eastern
      coast, protection of the remaining forest fragments is critical for their
      survival. Fifteen of the largest intact littoral forest fragments we identified,
      collectively representing 41.5% of remaining littoral forest, are among priority
      sites recommended to the government of Madagascar for plant conservation and
      incorporation into the protected-areas network.

PMID- 17181816
TI  - Quantifying relative extinction risks and targeting intervention for the orchid
      flora of a natural park in the European preAlps.
AB  - Conservation currently relies largely on hindsight because demographic studies
      identify population decline after the event. Nevertheless, the degree of
      aggregation within a population is an "instantaneous" characteristic with the
      potential to identify populations presently at greatest risk of genetic
      impoverishment (via Allee effects and in-breeding depression) and local decline.
      We sought to determine the relative extinction risk for sympatric orchid species
      throughout Monte Barro natural park (Lecco, Italy), based on an index of
      dispersion (I) calculated from the size and location of subpopulations (recorded
      with GPS and mapped with GIS). Three population dispersion types were identified:
      (1) highly aggregated and locally abundant (large subpopulations restricted to
      particular sites; e.g., Gymnadenia conopsea [L.] R.Br.; I=54.5); (2) widespread
      and moderately aggregated (opportunistic throughout the elevational range of the
      mountain; e.g., Listera ovata[L.] R.Br.; I=18.9); and (3) weakly aggregated and
      locally rare (small, highly diffuse subpopulations; e.g., endemic Ophrys
      benacensis [Reisigl] O. & E. Danesch & Ehrend.; I=4.4). Type 1 populations are
      more likely to respond to in situ intervention, whereas type 2 are relatively
      invasive species for which conservation intervention is not necessary, and type 3
      are rare species that are least likely to respond to habitat management, for
      which ex situ conservation and population reinforcement would be most
      appropriate. Although our methodology provides only a "snapshot" of aboveground
      patterns of population dispersion, it can help target the application of in situ
      and ex situ conservation activities proactively and is of particular utility for
      parks for which a rapid assessment of local extinction risks is needed.

PMID- 17181817
TI  - Biodiversity and human livelihood crises in the Malay Archipelago.

PMID- 17181818
TI  - The pigeon paradox: dependence of global conservation on urban nature.

PMID- 17181819
TI  - Perceived barriers to integrating social science and conservation.

PMID- 17181826
TI  - The humoral response to human factor VIII in hemophilia A mice.
AB  - BACKGROUND: Inhibitory antibodies (Abs) to factor VIII (FVIII inhibitors)
      constitute the most significant complication in the management of hemophilia A.
      The analysis of FVIII inhibitors is confounded by polyclonality and the size of
      FVIII. OBJECTIVES: The goal of this study was to dissect the polyclonal response
      to human FVIII in hemophilia A mice undergoing a dosage schedule that mimics
      human use. METHODS: Splenic B-cell hybridomas were obtained following serial i.v.
      injections of submicrogram doses of FVIII. Results of a novel, anti-FVIII domain
      specific enzyme-linked immunosorbent assay were compared to Ab isotype and anti
      FVIII inhibitory activity. RESULTS: The robust immune response resulted in the
      production of approximately 300 hybridomas per spleen. We characterized Abs from
      506 hybridomas, representing the most comprehensive analysis of a protein antigen
      to date. Similar to the human response to FVIII, anti-A2 and anti-C2 Abs
      constituted the majority of inhibitors. A novel epitope was identified in the A2
      domain by competition ELISA. Anti-A2 and anti-C2 Abs were significantly
      associated with IgG(1) and IgG(2a) isotypes, respectively. Because the IgG(2a)
      isotype is associated with enhanced Fc receptor-mediated effector mechanisms,
      this result suggests that anti-C2 Abs and inflammation may be linked.
      Additionally, we identified a novel class of Abs with dual specificity for the A1
      and A3 domains. Forty per cent of the Abs had no detectable inhibitory activity,
      indicating that they are prominent and potentially pathologically significant.
      CONCLUSION: The expanded delineation of the humoral response to FVIII may lead to
      improved management of hemophilia A through mutagenesis of FVIII B-cell epitopes.

PMID- 17181827
TI  - Recombinant factor VIIa and trauma: treatment that does not leave you in the
      cold.

PMID- 17181828
TI  - Methionine-loading and random homocysteine tests have no added value in risk
      assessment for venous and arterial thrombosis.

PMID- 17181829
TI  - End-stage renal disease: global demographics in 2005 and observed trends.

PMID- 17181831
TI  - Significant survival prolongation in pigs with fulminant hepatic failure treated
      with a novel microgravity-based bioartificial liver.
AB  - The aim of this study was to evaluate the efficacy and safety of our novel
      Innsbruck Bioartificial Liver (IBAL; US patent no. 10/641275), which contains
      aggregates of porcine hepatocytes grown under simulated microgravity, in a
      porcine model of fulminant hepatic failure (FHF). FHF was induced by a
      combination of 75-80% liver resection and ischemia of the remnant segments for 60
      min in 12 pigs. Two experimental groups were studied: the control group (n = 5)
      received standard intensive care and the study group (n = 5) received IBAL
      treatment. The survival of pigs with FHF was significantly prolonged by about
      150% with IBAL treatment as compared to controls (controls: 20.4 +/- 2.8 h, IBAL:
      51.0 +/- 2.2 h; P = 0.00184). In addition, intracranial pressure, blood ammonia,
      lactate, aspartate aminotransferase, and alkaline phosphatase levels were lower
      in the IBAL group than in controls, indicating metabolic activity of porcine
      hepatocytes in the bioreactor. No adverse effects were observed.

PMID- 17181830
TI  - Engineering of vascular grafts with genetically modified bone marrow mesenchymal
      stem cells on poly (propylene carbonate) graft.
AB  - Bone marrow mesenchymal stem cells (MSCs) have demonstrated their pluripotency to
      differentiate into different cell lineages and may be an alternative cell source
      for vascular tissue engineering. The objective of this study is to create small
      diameter vessels by seeding and culture of genetically modified MSCs onto a
      synthetic polymer scaffold produced by an electrospinning technique. A tubular
      scaffold (2 mm in diameter) with a microstructure of nonwoven fibers was produced
      by electrospinning of poly (propylene carbonate) (PPC). Rat MSCs obtained from
      bone marrow were expanded in culture and modified with vasculoprotective gene
      endothelial nitric oxide synthase (eNOS) or marker gene green fluorescent protein
      (GFP). These MSCs were seeded onto the electrospun fibrous grafts (internal
      diameter = 2 mm), and cultured in 5% CO(2) at 37 degrees C. The growth of MSCs in
      the scaffold was analyzed with scanning electron microscopy (SEM) and hematoxylin
      and eosin (H&E) staining. The gene transfer and transgenic gene expression were
      examined with fluorescence-activated cell sorting (FACS), immunochemical
      staining, reverse transcriptase-polymerase chain reaction (RT-PCR), and western
      blot. The production of nitric oxide (NO) by the engineered vessels was measured
      with an NO detection kit. Our data showed that the seeded cells integrated with
      the microfibers of the scaffold to form a three-dimensional cellular network,
      indicating a favorable interaction between this synthetic PPC scaffold with MSCs.
      High transduction efficiency was obtained with the use of concentrated retrovirus
      in the gene transfection of MSCs. The eNOS gene transcripts and protein were
      detected in the grafts seeded with eNOS-modified MSCs by RT-PCR and
      immunochemical staining. The amount of NO produced by grafts seeded with eNOS
      modified MSCs was comparable to that produced by native blood vessels, and it was
      significantly higher than that in the grafts seeded with nonmodified MSCs. In
      summary, the vascular graft produced by culture of eNOS gene-modified MSCs onto
      the electrospun tubular scaffolds shows promising results in terms of function.
      The use of MSCs and therapeutic genes in tissue engineering of blood vessels
      could be helpful in improving vessel regeneration and patency.

PMID- 17181832
TI  - Oxygen reduces accumulation of type IV collagen in endothelial cell subcellular
      matrix via oxidative stress.
AB  - Anchorage-dependent cells in culture attach initially to proteins adsorbed to the
      culture substrate from the medium, and produce and deposit a subcellular matrix
      during the course of the cultivation. The aim of this study was to determine
      whether the concentration of O(2) in the culture atmosphere affects the
      accumulation of type IV collagen and laminin under human endothelial-cell
      monolayers. Enzyme-linked immunoassays on decellularized polystyrene substrates
      showed less type IV collagen, but not less laminin, under cells incubated in the
      standard atmosphere (5% CO(2) in air, i.e., approximately 20% O(2)) compared to
      an atmosphere of 5% O(2) and 5% CO(2) in N(2). Type IV collagen accumulation was
      inhibited via oxidative stress, because the inhibitory effect of 20% O(2) was
      antagonized by antioxidant ascorbic acid, and mimicked by prooxidant pyrogallol
      and exogenous H(2)O(2). Measurements of endogenous H(2)O(2) accumulation
      demonstrated that endothelial cells partially adapt to the high O(2)
      concentration. These results may have implications in endothelium modeling in
      vitro and in engineering of endothelial cell sheets and endothelialized vascular
      grafts.

PMID- 17181833
TI  - Procedure-induced inflammation and endothelial cell activation in an artificially
      ventilated and circulated porcine double-lung model.
AB  - Systemic inflammation is induced during extracorporeal circulation, resulting in
      an increased bleeding tendency and endothelial cell activation. Lungs from seven
      piglets were perfused by autologous blood in an extracorporeal circuit, where the
      lungs and the left atrium were attached to polyvinyl chloride (PVC) tubings and
      the blood circulated by a roller pump. The trachea was intubated and attached to
      a ventilator. The lungs maintained good gas exchange, despite a slight increase
      in lactate levels. Plasma tPA increased slightly over time, suggesting
      endothelial cell activation. Activation of inflammatory systems was reflected in
      increased levels of plasma interleukin (IL)-6 and IL-10. A model for the study of
      lung endothelial activation during extracorporeal circulation has been shown to
      be reproducible. The lung tissue was shown to be capable of gas exchange and
      activation of endothelial cells and procedure-induced inflammation were noted.

PMID- 17181834
TI  - Numerical simulation of cardiovascular dynamics with left heart failure and in
      series pulsatile ventricular assist device.
AB  - This article presents a numerical model for investigations of the human
      cardiovascular circulation system response, where the function of the impaired
      left ventricle is augmented by the pumping action of a pulsatile ventricular
      assist device (VAD) connected in series to the native heart. The numerical model
      includes a module for detailed heart valve dynamics, which helps to improve the
      accuracy of simulation in studying the pulsatile type VAD designs. Simulation
      results show that, for the case with left ventricular (LV) failure, the VAD
      support successfully compensates the impaired cardiovascular response, and
      greatly reduces the after-load of the diseased ventricle, thus assisting possible
      recovery of the ventricle from the diseased condition. The effects of these
      conditions on pulmonary circulation are also shown. To investigate the effect of
      different pumping-activation functions (VAD motion profiles) on the
      cardiovascular response, three different VAD motion profiles are investigated.
      The numerical results suggest that Hermitian type motion profiles (smooth curves
      skewed toward early systole) have the advantage of requiring minimum power to the
      VAD, and producing the minimum after-load to the left ventricle, minimum
      ventricular wall stress, and minimum ventricular work to the diseased ventricle;
      while sawtooth type motions need slightly more power input, and induce slightly
      increased aortic pressure in diastole, thus improving coronary perfusion.

PMID- 17181835
TI  - Hemolytic performance of a MagLev disposable rotary blood pump (MedTech Dispo):
      effects of MagLev gap clearance and surface roughness.
AB  - Mechanical shaft seal bearing incorporated in the centrifugal blood pumps
      contributes to hemolysis and thrombus formation. In addition, the problem of
      durability and corrosion of mechanical shaft seal bearing has been recently
      reported from the safety point of view. To amend the shortcomings of the blood
      immersed mechanical bearings, a magnetic levitated centrifugal rotary blood pump
      (MedTech Dispo Model 1; Tokyo Medical and Dental University, Tokyo, Japan) has
      been developed for extracorporeal disposable application. In this study, the
      hemolytic performance of the MedTech Dispo Model 1 centrifugal blood pump system
      was evaluated, with special focus on the narrow blood path clearance at the
      magnetic bearing between rotor and stator, and on the pump housing surface
      roughness. A pump flow of 5 L/min against the head pressure of 100 mm Hg for 4 h
      was included in the hemolytic test conditions. Anticoagulated fresh porcine blood
      was used as a working fluid. The clearance of blood path at the magnetic bearing
      was in the range of 100-250 micro m. Pump housing surface roughness was
      controlled to be around Ra = 0.1-1.5 micro m. The lowest hemolytic results were
      obtained at the clearance of 250 micro m and with the polished surface (Ra = 0.1
      micro m) yielding the normalized index of hemolysis (NIH) of less than 0.001
      g/100 L, which was 1/5 of the Biopump BP-80 (Medtronic Inc., Minneapolis, MN,
      USA, and 1/4 of the BPX-80. In spite of rough surface and narrow blood path, NIH
      levels were less than clinically acceptable level of 0.005 g/100 L. The
      noncontact, levitated impeller system is useful to improve pump performance in
      blood environment.

PMID- 17181837
TI  - Tissue-engineered approach for the treatment of steroid-induced osteonecrosis of
      the femoral head: transplantation of autologous mesenchymal stem cells cultured
      with beta-tricalcium phosphate ceramics and free vascularized fibula.
AB  - Autologous mesenchymal stem cells (MSCs) cultured with beta-tricalcium phosphate
      (beta-TCP) ceramics and with a free vascularized fibula were transplanted into
      three patients with steroid-induced osteonecrosis of the femoral head. The
      average follow-up period was 34 months and the average patient age at the time of
      surgery was 28 years old. Fifteen milliliters of bone marrow was obtained from
      the patients 4 weeks before surgery, and was used for in vitro proliferation of
      MSCs. beta-TCP granules were immersed in the MSC suspension and the cells were
      further cultured for 2 weeks. Cultured MSCs/beta-TCP composite granules were
      implanted into the cavity that remained after curettage of necrotic bone; and
      finally, a free vascularized fibula was grafted. All hips showed preoperative
      collapse and radiographic progression was observed in two hips postoperatively.
      Osteonecrosis did not progress any further and early bone regeneration was
      observed. This tissue-engineered approach has potentials for the treatment of
      osteonecrosis. However, our results suggested that the present procedure could
      not be used for cases with severe preoperative collapse.

PMID- 17181836
TI  - In vivo biocompatibility of sulfonated PEO-grafted polyurethanes for polymer
      heart valve and vascular graft.
AB  - Sulfonated poly(ethylene oxide) (PEO)-grafted polyurethane (PU) (PU-PEO-SO(3))
      prepared by bulk modification was used to coat both PU heart valves and vascular
      grafts, and their in vivo biocompatibility was evaluated using a canine shunt
      method. The two devices were implanted for up to 39 days and retrieved at
      specific time points for the analysis of blood compatibility, biostability, and
      calcium deposition. When the surface of the retrieved specimens was examined
      using scanning electron microscopy, platelet adhesion and thrombus formation
      appeared to be significantly lesser formed on the PU-PEO-SO(3)-coated implants,
      compared with the untreated PUs. While molecular weights of untreated PUs were
      found by gel permeation chromatography to be decreased after 39 days from
      implantation, the same remained barely changed with the PU-PEO-SO(3)-coated ones.
      The inductively coupled plasma study indicated that the amount of deposited
      calcium was significantly reduced in the surface-modified PU implants. The
      efficacy of PU-PEO-SO(3)-coated implants in terms of blood compatibility,
      biostability, and calcification resistance may render them as a promising
      biomedical material in the application for blood/tissue-contacting tissues and
      organs.

PMID- 17181838
TI  - Late results of gelatin-resorcin-formalin glue-aided repair in acute type A
      aortic dissection.
AB  - Gelatin-resorcin-formalin (GRF) glue has been used to obliterate the false lumen
      of dissected aortas, resulting in reduced mortality. However, because of the
      cytotoxicity of formalin, the application of GRF remains controversial. In this
      study, a total of 138 consecutive patients with acute type A dissection since
      1995, who underwent emergency graft replacement, were reviewed. The mean age was
      65.5 years. The hospital mortality rate was 6.5%. In-hospital re-exploration rate
      and patency rate of the false lumen were 6.5% and 24.7%, respectively. The
      actuarial survival rates were 81.5% after 5 years and 54.8% after 10 years.
      Reoperation-free rates were 87.9% after 5 years and 72.3% after 10 years. Tissue
      necrosis or aneurismal degeneration was not demonstrated at reoperation. In
      conclusion, GRF glue demonstrats excellent tissue adhesion and hemostasis
      capability, and contributes to improve surgical results.

PMID- 17181839
TI  - A pressure-controlled rat ventilator with electronically preset respirations.
AB  - Major experimental surgery on laboratory animals requires adequate anesthesia and
      ventilation to keep the animal alive throughout the procedure. A ventilator is a
      machine that helps the anesthesized animal breathe through an endotracheal tube
      by pumping a volume of gas (oxygen, air, or other gaseous mixtures), comparable
      with the normal tidal volume, into the animal's lungs. There are two main
      categories of ventilators for small laboratory rodents: volume-controlled and
      pressure-controlled ones. The volume-controlled ventilator injects a preset
      volume into the animal's lungs, no matter the airways' resistance (with the peak
      inspiratory pressure allowed to vary), while the pressure ventilator controls the
      inspiratory pressure and allows the inspiratory volume to vary. Here we show a
      rat pressure ventilator with a simple expiratory valve that allows gas delivery
      through electronic expiration control and offers easy pressure monitoring and
      frequency change during ventilation.

PMID- 17181840
TI  - Specialist vs generalist management of colorectal cancer.

PMID- 17181841
TI  - Tumour-associated angiogenesis in human colorectal cancer.
AB  - Tumour angiogenesis is a critical step in the growth, metastatic spread and
      regrowth of colorectal cancer. Angiogenesis specific to tumour is a complicated
      process, the mechanisms of which remain unclear. Metastasis of colorectal cancer
      may result from passive entry into the circulation secondary to the effect of
      angiogenic factors. The survival and growth of colorectal tumour and thus their
      metastases are dependent on the balance of endogenous angiogenic and anti
      angiogenic factors such that the outcome favours increased angiogenesis.
      Angiogenesis has become an attractive target for anticancer drug development,
      based on its important roles in tumour growth, invasion and metastasis. Several
      growth factors have been identified that regulate angiogenesis in colorectal
      cancer; the most important of these are vascular endothelial growth factors
      (VEGF), and of the several angiogenic factors, VEGF expression at the deepest
      invasive site of tumour is the most statistically significant prognostic
      indicator in advanced colorectal carcinoma. In this review article, we provide an
      overview on angiogenic factors and their receptors, and discuss the role of newly
      identified tumour endothelial markers (TEMs) that are involved in tumour
      associated angiogenesis in colorectal cancer.

PMID- 17181843
TI  - Influence of caseload and surgical speciality on outcome following surgery for
      colorectal cancer: a review of evidence. Part 1: short-term outcome.
AB  - OBJECTIVE: An association between caseload and outcome has been reported for
      complex surgical procedures. We systematically reviewed recent literature to
      determine whether caseload and surgical speciality are associated with short-term
      outcome following colorectal cancer surgery. METHOD: We searched the MEDLINE and
      Cochrane Library databases for relevant publications starting in 1992. We
      selected hospital caseload and type, and surgeon's caseload, education and
      experience as variables of interest. Measures of outcome were postoperative
      morbidity, in-hospital and 30-day mortality, and for rectal cancer anastomotic
      leak. We stratified the 35 reviewed studies by tumor location: colonic cancer,
      rectal cancer, or colorectal cancer and described the studies individually. A
      meta-analysis was performed only when it was considered appropriate. RESULTS: For
      colonic cancer, postoperative morbidity was associated with surgeon's caseload
      and education. Postoperative mortality was strongly associated with hospital
      caseload (OR 0.64, 95% CI 0.55-0.73), and surgeon's caseload (OR 0.50, 95% CI
      0.39-0.64). It was also influenced by surgeon's education and experience. For
      rectal cancer, we found no evidence of an association between the selected
      variables and short-term outcome, including frequency of anastomotic leak. For
      colorectal cancer, there was evidence for an association between postoperative
      morbidity and hospital caseload. CONCLUSION: Our review offers evidence for a
      positive association between high hospital caseload, surgeon's caseload, sub
      speciality and experience and improved short-term outcome in colonic cancer
      surgery. We failed to find evidence of a relationship for rectal cancer surgery,
      possibly owing to methodological artifacts. No study reported an inverse
      relation.

PMID- 17181842
TI  - Risk of dysplasia and adenocarcinoma following restorative proctocolectomy for
      ulcerative colitis.
AB  - OBJECTIVE: Restorative proctocolectomy (RPC) with or without mucosectomy is the
      treatment of choice for most patients with ulcerative colitis (UC) requiring
      surgery. The ileal mucosa in the reservoir and the anorectal columnar epithelium
      below the ileo-anal anastomosis are at risk of neoplastic transformation. METHOD:
      The literature has been reviewed to identify patients developing this
      complication and an attempt has been made to develop a rational follow-up policy
      based on the data available. RESULTS: Dysplasia in the ileal reservoir is rare.
      It is associated with histological type C changes, sclerosing cholangitis and
      unremitting pouchitis in the ileal mucosa and to the presence of sclerosing
      cholangitis. Nine patients who have developed adenocarcinoma in the residual
      anorectal mucosa and seven in the reservoir have been reported in the literature.
      A further hitherto unreported patient treated by the authors brings the total to
      17 patients. Twelve of these had histopathological data on either dysplasia or
      carcinoma in the original operative specimen. The time intervals from the onset
      of UC and from the RPC to the development of cancer were 120-528 (median 246) and
      16-216 (median 60) months respectively. Cancer appeared to be related to the
      duration of disease rather than to the interval from RPC. In all the reported
      patients the interval from the onset of UC was 10 years. CONCLUSION: Based on
      these data a surveillance programme should begin at 10 years from the onset of
      disease. Patients with dysplasia or carcinoma in the original specimen, those
      with type C ileal mucosal changes and patients with sclerosing cholangitis should
      be selected for surveillance. This will involve multiple biopsies of the ileal
      reservoir and the anorectal mucosa below the ileo-anal anastomosis.

PMID- 17181844
TI  - Influence of caseload and surgical speciality on outcome following surgery for
      colorectal cancer: a review of evidence. Part 2: long-term outcome.
AB  - OBJECTIVE: We reviewed recent literature to assess the impact of hospital
      caseload, surgeon's caseload and education on long-term outcome following
      colorectal cancer surgery. METHOD: We searched the MEDLINE and Cochrane Library
      databases for relevant literature starting from 1992. We selected hospital
      caseload, surgeon's caseload and surgeon's education, type of hospital, and
      surgeon's experience as variables of interest. Measures of outcome were
      recurrence-free survival and overall survival, and for rectal cancer frequency of
      permanent stoma. We reviewed the 34 studies according to tumour location: colonic
      cancer, rectal cancer, or colorectal cancer. We described the studies
      individually and performed a meta-analysis whenever it was considered
      appropriate. RESULTS: For colonic cancer, overall survival improved with
      increasing hospital caseload, odds ratio (OR) 1.22 [95% confidence interval (CI)
      1.16-1.28], and surgeon's education. For rectal cancer, overall survival improved
      with increasing hospital caseload, OR 1.38 (95% CI 1.19-1.60), and, possibly by
      surgeon' education and experience. Cancer-free survival was strongly influenced
      by surgeon's education. The colostomy rate was less in high caseload hospitals,
      OR 0.76 (95% CI 0.68-0.85). For colorectal cancer, overall survival improved with
      surgeon's education. CONCLUSION: The data have provided evidence that long-term
      survival following colorectal cancer surgery in general improved significantly
      with increasing hospital caseload and surgeon's education.

PMID- 17181845
TI  - Indwelling trans-anastomotic rectal tubes in colorectal surgery: a survey of
      usage in UK and Ireland.
AB  - BACKGROUND: The use of rectal tubes in colorectal surgery appears to be a matter
      of individual choice, with little documented evidence to support their use. This
      study assesses the current practice of rectal tubes amongst consultant members of
      the Association of Coloproctology of Great Britain & Ireland (ACPGBI). METHODS: A
      piloted questionnaire was sent to practising ACPGBI consultant members listed in
      the 2003-04 directory. Statistical analysis was performed using SPSS software and
      Fishers exact test. RESULTS: Three hundred and thirty-nine replies were received
      from 579 posted questionnaires (response rate = 58.5%). Rectal tubes were used by
      116 (35%) of responding surgeons. Rectal tubes were more commonly used by
      surgeons with less than 10 years practice as a consultant (P < 0.005). The main
      indications for tube placement were following ileo-anal or colonic pouch surgery
      (73%), after any anterior resection (36%) (rectal tubes were reserved for only
      low anterior resections by 16% of surgeons) and in the rectal stump after total
      or subtotal colectomy for acute colitis (11%). Twenty-three percent of these
      practising surgeons would use a rectal tube as an alternative to a diverting
      stoma, predominantly in selected patients following ileo-anal pouch surgery. A
      Foley catheter was the commonest type of tube used (70%) and this was usually
      placed above the anastomosis (80%). Rectal tubes were left in situ for a median
      of 5 days (range = 1-13 days). Three surgeons (2.6%) reported serious
      complications including tube perforation of the bowel or anastomosis. Several
      different mechanisms were suggested for the purpose and functioning of the rectal
      tube, the commonest being to decompress the rectum and/or pouch. CONCLUSION:
      Rectal tube placement is simple and safe and is used by a third of colorectal
      surgeons in UK and Ireland. Given their simplicity, the efficacy of rectal tubes
      in reducing local anastomotic complications requires further evaluation within
      the confines of a randomised controlled trial.

PMID- 17181846
TI  - Prospective randomized, double-blind, placebo-controlled study of pre- and
      postoperative administration of a COX-2-specific inhibitor as opioid-sparing
      analgesia in major colorectal surgery.
AB  - PURPOSE: To demonstrate the opioid-sparing effect and reduction in postoperative
      ileus obtained with valdecoxib 40 mg administered pre- and postoperatively in
      patients undergoing colorectal resection. METHODS: Patients for elective
      colorectal resection from December 2002 to June 2004 were randomized to receive
      either valdecoxib or placebo with standard patient-controlled analgesia (PCA)
      morphine. In the study arm, the first dose of valdecoxib 40 mg was administered
      orally as close as possible to 1 h prior to the start of surgery. Each subsequent
      dose was administered at 24-h intervals up to 120 h. Patients in the control arm
      were served placebos at the same time-points. RESULTS: Forty patients were
      enrolled in the study arm and 39 (excluding one protocol violation) in the
      control arm. The groups were comparable in age, sex, American Society of
      Anesthesiology status, body mass index, incision length, and duration and types
      of operations. Mean PCA doses at 12 and 24 h were 18.6 and 28.3 mg in the study
      arm vs 26.2 and 41.2 mg in controls, representing a one-third opioid reduction.
      Bowel sound and movement first appeared at medians of 12 and 72 h in the study
      arm vs 24 and 84 h, respectively, in controls (P < 0.05). Tolerance of solid diet
      was at a median of 60 h and discharge at a median of 4 days in the study arm vs
      72 h and 6 days in controls (P < 0.05 and P < 0.01, respectively). Seven (18%)
      morbidities occurred in the control vs six (15%) in the study arm. CONCLUSIONS:
      Patients treated with a cyclo-oxygenase 2-specific inhibitor have a shorter
      recovery time when compared with patients on a standard postoperative PCA
      morphine-only regimen after colorectal resection.

PMID- 17181847
TI  - The use of a dedicated rectosigmoidoscope for ultrasound staging of tumours of
      the upper and middle third of the rectum.
AB  - OBJECTIVE: Tumours of the upper rectum, and many in the middle third, are not
      accessible to endorectal ultrasound staging because of the difficulty in reaching
      all sites of the rectum with a rigid probe. The aim of this prospective study was
      to assess whether using a dedicated rectosigmoidoscope, endorectal
      ultrasonography (ERUS) can accurately stage any rectal lesion irrespective of its
      distance from the anal verge. METHOD: A total of 173 consecutive patients with a
      primary rectal tumour were included. A rotating, high multifrequency (5.0-10 MHz)
      endoprobe was introduced through a dedicated rectosigmoidoscope and advanced
      above the lesion. A computer allowed for three-dimensional (3D) reconstruction of
      2D images. Treatment was selected on the basis of 3D-ERUS findings. ERUS staging
      was correlated with pathological staging. RESULTS: The depth of invasion was
      correctly determined by 3D-ERUS in 78.2% of tumours of the lower rectum, 76.4% of
      tumours extending between the lower and middle third of the rectum, 80.9% of
      tumours of the middle third of the rectum, 78.5% of tumours extending between the
      middle and upper third of the rectum and 78.9% of tumours of the upper rectum.
      The accuracy for the absence of lymph node metastases was 81.2% for tumours of
      the lower rectum, 78.5% for tumours extending between the lower and middle third
      of the rectum, 85.7% for tumours of the middle third of the rectum, 83.3% for
      tumours extending between the middle and upper third of the rectum and 78.5% for
      tumours of the upper rectum. Analysis showed that there was no difference between
      the various tumour sites. CONCLUSION: Our findings indicate that using a
      dedicated proctosigmoidoscope, tumours of the upper and middle third of the
      rectum are equally accessible to ultrasonographic evaluation. The distance of the
      tumour from the anal verge does not influence the accuracy of examinations
      considered adequate by the operator.

PMID- 17181848
TI  - Investigation of stimulus position in the production of the strength duration
      curve of the external anal sphincter muscle in women with anorectal dysfunction.
AB  - OBJECTIVE: The strength duration test (SDT) is a minimally invasive test of the
      innervation of a muscle and has been successfully adapted for use on the external
      anal sphincter (EAS). The SDT has previously been performed on the EAS placing a
      stimulating probe in the 3 o'clock position. The aim of this study was to
      determine whether there was any variation in the strength duration curves (SDC)
      produced at different positions around the EAS. PATIENTS AND METHODS: Thirty-one
      patients with anorectal dysfunction attended our Institution for Anorectal
      Physiology Studies and were recruited to the study. After undergoing anal
      manometry, pudendal nerve terminal motor latency measurement and endoanal
      ultrasonography, the SDT was performed in four stimulus positions (3, 6, 9 and 12
      o'clock). The sequence of positions was randomly selected. RESULTS: Four SDCs
      were obtained successfully in 25 patients. There was no significant difference
      seen between the four positions at the longer current durations (1-100 ms).
      Significant differences occurred at the shortest current durations (0.3 and 0.1
      ms) when comparing adjacent stimulus positions except between the 6 and 9 o'clock
      positions, which were comparable. When opposing positions were compared (3-9 and
      6-12 o'clock) at these short durations no significant difference was found.
      CONCLUSION: There was no significant difference between the SDC produced at 3 and
      9 o'clock. These positions closely correspond to where the pudendal nerves enter
      the EAS. It therefore appears acceptable to perform the SDT in either of these
      positions, though 3 o'clock remains our preferred position.

PMID- 17181849
TI  - The incidence of anastomotic leaks in patients undergoing colorectal surgery.
AB  - BACKGROUND: There is evolving interest in auditing and credentialling the
      performance of surgeons. The incidence of anastomotic leakage has been proposed
      as a measure of performance following colorectal surgery. The aim of this study
      was to evaluate the incidence and risk factors associated with anastomotic
      leakage in patients undergoing resections of the colon and rectum. METHODS: A
      prospective database was developed for all patients undergoing colorectal
      surgery. Anastomotic leakage was defined prior to the commencement of the study.
      A logistic regression analysis was performed to determine independent predictors
      of leakage. The variables analysed included age, sex, American Society of
      Anesthesiology (ASA) score, anatomical location, pathology, emergency surgery,
      type of anastomosis, a covering stoma and radiotherapy. Significance was defined
      as the probability of a type 1 error of < 5%. The results are presented as odds
      ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: There were 1598
      patients who underwent 1639 anastomoses. Their mean age was 63 years, 34% of
      patients were ASA 3 or 4, and 16% of the operations were emergencies. Anastomotic
      leaks occurred in 2.4% (40/1639) of anastomoses. The leak rate for
      intraperitoneal anastomoses was 1.5% (19/1283) vs 6.6% for extraperitoneal
      anastomoses (21/316). Half of these leaks (20/40) were managed with re-operation
      or percutaneous drainage procedures. Ultra-low anterior resections were
      associated with the highest leak rate (8%, 18/225). A logistic regression
      analysis identified a covering stoma (P = 0.0001, OR 5.078, 95% CI 2.527-10.23)
      and diverticular disease (P = 0.037, OR 2.304, 95% CI 1.053-5.042) as independent
      predictors of a leak. CONCLUSIONS: Within this surgical unit, the incidence of
      leaks from intraabdominal anastomoses was relatively low. However, leaks in
      patients undergoing extraperitoneal anastomoses continue to be a major cause of
      morbidity and mortality.

PMID- 17181850
TI  - Anorectal three-dimensional endosonography and anal manometry in assessing
      anterior rectocele in women: a new pathogenesis concept and the basic surgical
      principle.
AB  - OBJECTIVE: The anatomy of the anal canal, the anorectal junction and the lower
      rectum was studied with 3-D ultrasound. METHOD: Seventeen women with normal bowel
      transit, without rectocele (group 1) and 17 female patients with a large anterior
      rectocele (group 2) were examined with a B&K Medical Rawk. Mean age was 44.5 and
      51.6 years respectively. In group 1, one (5.8%) patient was nuliparous, five
      (29.4%) had a caesarian section, 11 (64.7%) had a vaginal delivery while in group
      2, two (11.7%) patients were nuliparous, four (23.5%) had a caesarian section and
      11 (64.7%) had a vaginal delivery. Images were reconstructed in midline
      longitudinal (ML) and transverse (T) planes. The external (EAS) and internal
      (IAS) anal sphincters were measured in both projections. RESULTS: In the ML
      plane, the EAS length was longer in group 1 (1.94 cm vs 1.61 cm, P < 0.05), the
      gap length was shorter (1.54 cm vs 1.0 cm P < 0.01) and the wall thickness was
      shorter in group 2 (0.40 cm vs 0.50 cm P < 0.01). The IAS (0.18 cm vs 0.23 cm P <
      0.01) and EAS thickness (0.68 cm vs 0.77 cm, P < 0.05) (left lateral of the
      posterior quadrant) was greater in group 2. In group 1, the anterior upper anal
      canal wall in normal females was an extension of the rectal wall and the circular
      muscle was thicker in the mid-anal canal to form the IAS. In group 2, however,
      the wall layers were not identified and the IAS was found to be more distal. The
      differences were not statistically significant in the anal canal resting and
      squeeze pressures in the two groups. CONCLUSION: Obstetric trauma does not seem
      to play any role in rectocele pathogenesis because the anal sphincter muscles are
      anatomically and functionally normal and rectocele is also present in nuliparous
      and in women with caesarian sections. It seems that it is associated with the
      absence of EAS and thinner IAS in the anterior upper anal canal. Herniation
      starts at the upper anal canal extending to the lower rectum in high or large
      rectoceles and maybe produced by rectal intussusception because of excessive and
      prolonged straining during defecation. In fact, the denomination 'rectocele'
      should be changed to 'anorectocele'.

PMID- 17181851
TI  - Telephonic management of rectal bleeding in young adults: a prospective
      randomized controlled trial.
AB  - OBJECTIVE: The majority of young adults referred with rectal bleeding to a
      colorectal specialist clinic have a very low risk of serious disease such as
      cancer, and a high chance of gaining symptom relief by simple dietary changes. To
      determine whether young low-risk patients with rectal bleeding can be managed
      with a structured telephonic interview and dietary advice, rather than an
      outpatient visit. METHOD: A single-blinded, prospective, randomized controlled
      trial was performed in two stages. Patients under 40 years with rectal bleeding
      only were offered inclusion. Part-I trial: Patients were interviewed on telephone
      by the colorectal nurse specialist (CNS) and randomized to receive dietary advice
      (Advice Group) or not (Control Group). All patients were seen in clinic 6 weeks
      later by a doctor 'blinded' to their trial status. Part-II trial: Patients were
      interviewed on telephone by the CNS and again randomized to an Advice Group or a
      Control Group. The Control Group were seen in clinic 6 weeks later. The Advice
      Group were telephoned again 6 weeks later, and if their bleeding had stopped,
      were not brought to clinic. All patients were tracked for a year after the study
      to ensure no adverse diagnoses came to light. RESULTS: Part-I trial: 63 of 89
      eligible patients were contactable and none refused the study. Seventy per cent
      of the Advice Group compared with 33% (P = 0.001) of the Control Group had
      symptomatic improvement when seen in clinic. Approximately 30% of each group
      required further treatment. Part-II trial: 54 of 94 eligible patients were
      contactable. However a further nine declined to enter the trial; 90% of patients
      in the Advice Group had improved at 6 weeks as judged by telephone interview
      compared with 56% of patients in the Control Group (P = 0.024) who were seen in
      clinic. The 90% of patients who improved in the Advice Group did not need to come
      to clinic to be seen. In both parts of the trial, the CNS identified a small
      number of patients with urgent symptoms at interview and brought them to clinic.
      The majority had anal fissures or haemorrhoids although in Part-II, one patient
      had ulcerative colitis and one had colorectal cancer. CONCLUSION: Telephonic
      consultation is an effective way of identifying those patients with urgent
      symptoms among a cohort of young adults referred to the hospital with rectal
      bleeding. Telephonic dietary advice leads to resolution of rectal bleeding in the
      majority of patients without urgent symptoms.

PMID- 17181852
TI  - The effect of surgery on quality of life in patients with faecal incontinence of
      obstetric origin.
AB  - OBJECTIVE: To evaluate the results of surgery in the treatment of faecal
      incontinence of obstetric origin and assess the effect of treatment on the
      quality of life of these patients. PATIENTS AND METHODS: A consecutive series of
      43 patients, who had undergone surgery for severe faecal incontinence of
      obstetric aetiology between March 1990 and March 2004, was studied. The following
      studies were carried out: clinical evaluation, anorectal manometry, anal
      endosonography (from 1996 on) and measurement of the pudendal nerve terminal
      motor latency. The degree of incontinence, both preoperative and at the end of
      follow-up was evaluated using the Cleveland Clinic Score (CCS). Quality of life
      assessment was made using the Fecal Incontinence Quality of Life Scale (FIQL).
      RESULTS: The study was completed on 35 (87%) of the 43 patients. The mean age in
      the series was 53 years, (range 28-73). After an average follow-up of 50.4 months
      (range 4-132) the mean CCS had reduced significantly, passing from 16 (range 8
      20) to 6 (range 0-18; P < 0.001). Pudendal neuropathy was found to be a factor of
      poor prognosis. The results of the quality of life questionnaire at the end of
      follow-up were: lifestyle 3.5 (SD 0.65), coping/behaviour 3.1 (SD 0.81),
      depression/self perception 3.7 (SD 0.75) and embarrassment 3.3 (SD 0.91). There
      is a statistically significant linear relationship between incontinence measured
      on the CCS and quality of life. For the 14 patients undergoing surgery since the
      publication of the FIQL questionnaire, it was possible to complete the
      questionnaire preoperatively, with significant improvement found on each of the
      four scales (lifestyle 1.7 vs 3.5; coping/behaviour 1.4 vs 3.2; depression 2.2 vs
      3.8; embarrassment 1.8 vs 3.2; P < 0.001). CONCLUSION: Surgical treatment of
      faecal incontinence of obstetric origin achieves good results in a high
      percentage of patients and has a positive effect on their quality of life. The
      existence of prolonged preoperative pudendal nerve motor latency indicates a poor
      prognosis.

PMID- 17181853
TI  - Behavioral factors to include in guidelines for lifelong oral healthiness: an
      observational study in Japanese adults.
AB  - BACKGROUND: The aim of this study was to determine which behavioral factors to
      include in guidelines for the Japanese public to achieve an acceptable level of
      oral healthiness. The objective was to determine the relationship between oral
      health related behaviors and symptoms related to oral disease and tooth loss in a
      Japanese adult community. METHODS: Oral health status and lifestyle were
      investigated in 777 people aged 20 years and older (390 men and 387 women).
      Subjects were asked to complete a postal questionnaire concerning past diet and
      lifestyle. The completed questionnaires were collected when they had health
      examinations. The 15 questions included their preference for sweets, how many
      between-meal snacks they usually had per day, smoking and drinking habits,
      presence of oral symptoms, and attitudes towards dental visits. Participants were
      asked about their behaviors at different stages of their life. The oral health
      examinations included examination of the oral cavity and teeth performed by
      dentists using WHO criteria. Odds ratios were calculated for all subjects, all 10
      year age groups, and for subjects 30 years or older, 40 years or older, 50 years
      or older, and 60 years or older. RESULTS: Frequency of tooth brushing (OR =
      3.98), having your own toothbrush (OR = 2.11), smoking (OR = 2.71) and bleeding
      gums (OR = 2.03) were significantly associated with number of retained teeth in
      males. Frequency of between-meal snacks was strongly associated with number of
      retained teeth in females (OR = 4.67). Having some hobbies (OR = 2.97), having a
      family dentist (OR = 2.34) and consulting a dentist as soon as symptoms occurred
      (OR = 1.74) were significantly associated with number of retained teeth in
      females. Factors that were significantly associated with tooth loss in both males
      and females included alcohol consumption (OR = 11.96, males, OR = 3.83, females),
      swollen gums (OR = 1.93, males, OR = 3.04, females) and toothache (OR = 3.39,
      males, OR = 3.52, females). CONCLUSION: Behavioral factors that were associated
      with tooth retention were frequency of eating snacks between meals, tooth
      brushing frequency, having one's own toothbrush, smoking and drinking habits,
      having hobbies, having a family dentist and when they had dental treatment.
      Clinical factors included bleeding gums, swollen gums, and toothache.

PMID- 17181854
TI  - GOAnnotator: linking protein GO annotations to evidence text.
AB  - BACKGROUND: Annotation of proteins with gene ontology (GO) terms is ongoing work
      and a complex task. Manual GO annotation is precise and precious, but it is time
      consuming. Therefore, instead of curated annotations most of the proteins come
      with uncurated annotations, which have been generated automatically. Text-mining
      systems that use literature for automatic annotation have been proposed but they
      do not satisfy the high quality expectations of curators. RESULTS: In this paper
      we describe an approach that links uncurated annotations to text extracted from
      literature. The selection of the text is based on the similarity of the text to
      the term from the uncurated annotation. Besides substantiating the uncurated
      annotations, the extracted texts also lead to novel annotations. In addition, the
      approach uses the GO hierarchy to achieve high precision. Our approach is
      integrated into GOAnnotator, a tool that assists the curation process for GO
      annotation of UniProt proteins. CONCLUSION: The GO curators assessed GOAnnotator
      with a set of 66 distinct UniProt/SwissProt proteins with uncurated annotations.
      GOAnnotator provided correct evidence text at 93% precision. This high precision
      results from using the GO hierarchy to only select GO terms similar to GO terms
      from uncurated annotations in GOA. Our approach is the first one to achieve high
      precision, which is crucial for the efficient support of GO curators. GOAnnotator
      was implemented as a web tool that is freely available at
      http://xldb.di.fc.ul.pt/rebil/tools/goa/.

PMID- 17181855
TI  - Enhanced diffusion of uranium and thorium linked to crystal plasticity in zircon.
AB  - The effects of crystal-plasticity on the U-Th-Pb system in zircon is studied by
      quantitative microstructural and microchemical analysis of a large zircon grain
      collected from pyroxenite of the Lewisian Complex, Scotland. Electron backscatter
      diffraction (EBSD) mapping reveals a c.18 degree variation in crystallographic
      orientation that comprises both a gradual change in orientation and a series of
      discrete low-angle (<4 degrees) boundaries. These microstructural data are
      consistent with crystal-plastic deformation of zircon associated with the
      formation and migration of dislocations. A heterogeneous pattern of dark
      cathodoluminescence, with the darkest domains coinciding with low-angle
      boundaries, mimics the deformation microstructure identified by EBSD. Geochemical
      data collected using the Sensitive High Resolution Ion MicroProbe (SHRIMP) shows
      a positive correlation between concentrations of the elements U, Th and Pb
      (ranging from 20-60 ppm, 30-110 ppm, and 14-36 ppm, respectively) and Th/U ratio
      (1.13-1.8) with the deformation microstructure. The highest measured
      concentrations and Th/U coincide with low-angle boundaries. This enrichment is
      interpreted to reflect enhanced bulk diffusion of U and Th due to the formation
      and migration of high-diffusivity dislocations. 207Pb/206Pb ages for individual
      analyses show no significant variation across the grain, and define a concordant,
      combined mean age of 2451 +/- 14 Ma. This indicates that the grain was deformed
      shortly after initial crystallization, most probably during retrograde Inverian
      metamorphism at amphibolite facies conditions. The elevated Th over U and
      consistent 207Pb/206Pb ages indicates that deformation most likely occurred in
      the presence of a late-stage magmatic fluid that drove an increase in the Th/U
      during deformation. The relative enrichment of Th over U implies that Th/U ratio
      may not always be a robust indicator of crystallization environment. This study
      provides the first evidence of deformation-related modification of the U-Th
      system in zircon and has fundamental implications for the application and
      interpretation of zircon trace element data.

PMID- 17181856
TI  - Systematic interpretation of microarray data using experiment annotations.
AB  - BACKGROUND: Up to now, microarray data are mostly assessed in context with only
      one or few parameters characterizing the experimental conditions under study.
      More explicit experiment annotations, however, are highly useful for interpreting
      microarray data, when available in a statistically accessible format. RESULTS: We
      provide means to preprocess these additional data, and to extract relevant traits
      corresponding to the transcription patterns under study. We found correspondence
      analysis particularly well-suited for mapping such extracted traits. It
      visualizes associations both among and between the traits, the hereby annotated
      experiments, and the genes, revealing how they are all interrelated. Here, we
      apply our methods to the systematic interpretation of radioactive (single
      channel) and two-channel data, stemming from model organisms such as yeast and
      drosophila up to complex human cancer samples. Inclusion of technical parameters
      allows for identification of artifacts and flaws in experimental design.
      CONCLUSION: Biological and clinical traits can act as landmarks in transcription
      space, systematically mapping the variance of large datasets from the predominant
      changes down toward intricate details.

PMID- 17181857
TI  - Gene function and expression level influence the insertion/fixation dynamics of
      distinct transposon families in mammalian introns.
AB  - BACKGROUND: Transposable elements (TEs) represent more than 45% of the human and
      mouse genomes. Both parasitic and mutualistic features have been shown to apply
      to the host-TE relationship but a comprehensive scenario of the forces driving TE
      fixation within mammalian genes is still missing. RESULTS: We show that intronic
      multispecies conserved sequences (MCSs) have been affecting TE integration
      frequency over time. We verify that a selective economizing pressure has been
      acting on TEs to decrease their frequency in highly expressed genes. After
      correcting for GC content, MCS density and intron size, we identified TE-enriched
      and TE-depleted gene categories. In addition to developmental regulators and
      transcription factors, TE-depleted regions encompass loci that might require
      subtle regulation of transcript levels or precise activation timing, such as
      growth factors, cytokines, hormones, and genes involved in the immune response.
      The latter, despite having reduced frequencies of most TE types, are
      significantly enriched in mammalian-wide interspersed repeats (MIRs). Analysis of
      orthologous genes indicated that MIR over-representation also occurs in dog and
      opossum immune response genes, suggesting, given the partially independent origin
      of MIR sequences in eutheria and metatheria, the evolutionary conservation of a
      specific function for MIRs located in these loci. Consistently, the core MIR
      sequence is over-represented in defense response genes compared to the background
      intronic frequency. CONCLUSION: Our data indicate that gene function, expression
      level, and sequence conservation influence TE insertion/fixation in mammalian
      introns. Moreover, we provide the first report showing that a specific TE family
      is evolutionarily associated with a gene function category.

PMID- 17181858
TI  - 17Beta-estradiol effects on human coronaries and grafts employed in myocardial
      revascularization: a preliminary study.
AB  - BACKGROUND: This study was undertaken to compare the in vitro effects of 17beta
      estradiol on human epicardial coronary arteries, resistance coronary arteries and
      on arterial vessels usually employed as grafts in surgical myocardial
      revascularization. METHODS: Coronary artery rings (descending coronary artery,
      right coronary artery, circumflex coronary artery, first septal branch) and
      arterial graft rings (internal thoracic artery, gastro-epiploic artery) obtained
      from human heart donors with heart not suitable to cardiac transplantation were
      connected to force transducer for isometric force recording. Precontracted
      specimens with and without endothelium were exposed to increasing concentration
      of 17beta-estradiol (3-30-300-3000 nmol/l) and to vehicle (0.1% v/v ethanol). We
      also evaluated the effects of 17beta-estradiol on vessels before and 20 minutes
      after exposure to L-monomethyl-arginine and indomethacin. RESULTS: 17beta
      estradiol induced a significant relaxation in all precontracted vessels (mean
      maximum effect: 78,6% +/- 8,5). This effect was not different among the different
      rings and was not related to the presence of endothelium. N-monomethyl-L-arginine
      and indomethacin did not modify 17beta-estradiol relaxant effect. CONCLUSION: The
      vasodilator action of the 17beta-estradiol is similar on coronary arteries,
      resistance coronary arteries and arterial vessels usually employed as grafts in
      myocardial revascularization.

PMID- 17181859
TI  - Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti
      inflammatory drugs, and breast cancer risk.
AB  - INTRODUCTION: The association between use of nonsteroidal anti-inflammatory drugs
      (NSAIDs) and breast cancer risk remains unclear. Inconsistencies in previously
      reported findings may be partly due to differences in expression of
      cyclooxygenase (COX)-2. We hypothesized that genetic polymorphisms (COX-2 .926,
      COX-2 .5209, and COX-2 .8473) may reduce overall breast cancer risk or risk for
      subtypes of breast cancer by modulating the inflammatory response and may
      interact with aspirin or any NSAID use. METHODS: We conducted a population-based,
      case-control study in which we genotyped 1,067 breast cancer cases and 1,110
      control individuals included in the Long Island Breast Cancer Study Project.
      RESULTS: No major effects of the three COX-2 variant alleles on breast cancer
      risk were found. A total of eight distinct haplotypes and 18 diplotypes were
      observed in the population. Overall, no significant associations between COX-2
      haplotypes/diplotypes and breast cancer risk were observed. Among women who used
      aspirin or any NSAID there was little evidence for an interaction with the at
      risk COX-2 genotypes, with one exception. Among women with hormone receptor
      positive breast cancer, the reduced risk for any NSAID use was only evident among
      those who had at least one variant C allele of COX-2 .8473 (odds ratio = 0.7, 95%
      confidence interval = 0.5 to 1.0; P for the interaction = 0.02). There was no
      corresponding interaction for aspirin use, possibly because of limited power.
      CONCLUSION: These data provide modest evidence that the C allele of COX-2 .8473
      may interact with NSAIDs to reduce risk for hormone receptor positive breast
      cancer.

PMID- 17181862
TI  - Seasonal variations in pore water and sediment geochemistry of littoral lake
      sediments (Asylum Lake, MI, USA).
AB  - BACKGROUND: Seasonal changes in pore water and sediment redox geochemistry have
      been observed in many near-surface sediments. Such changes have the potential to
      strongly influence trace metal distribution and thus create seasonal fluctuations
      in metal mobility and bioavailability. RESULTS: Seasonal trends in pore water and
      sediment geochemistry are assessed in the upper 50 cm of littoral kettle lake
      sediments. Pore waters are always redox stratified, with the least compressed
      redox stratification observed during fall and the most compressed redox
      stratification observed during summer. A 2-step sequential sediment extraction
      yields much more Fe in the first step, targeted at amorphous Fe(III) (hydr)oxides
      (AEF), then in the second step, which targets Fe(II) monosulfides. Fe extracted
      in the second step is relatively invariant with depth or season. In contrast, AEF
      decreases with sediment depth, and is seasonally variable, in agreement with
      changes in redox stratification inferred from pore water profiles. A 5-step
      Tessier extraction scheme was used to assess metal association with operationally
      defined exchangeable, carbonate, iron and manganese oxide (FMO), organic/sulfide
      and microwave-digestible residual fractions in cores collected during winter and
      spring. Distribution of metals in these two seasons is similar. Co, As, Cd, and U
      concentrations approach detection limits. Fe, Cu and Pb are mostly associated
      with the organics/sulfides fraction. Cr and Zn are mostly associated with FMO. Mn
      is primarily associated with carbonates, and Co is nearly equally distributed
      between the FMO and organics/sulfide fractions. CONCLUSION: This study clearly
      demonstrates that near-surface lake sediment pore water redox stratification and
      associated solid phase geochemistry vary significantly with season. This has
      important ramifications for seasonal changes in the bioavailability and mobility
      of trace elements. Without rate measurements, it is not possible to quantify the
      contribution of various processes to natural organic matter degradation. However,
      the pore water and solid phase data suggest that iron reduction and sulfate
      reduction are the dominant pathways in the upper 50 cm of these sediments.

PMID- 17181860
TI  - Protease gene families in Populus and Arabidopsis.
AB  - BACKGROUND: Proteases play key roles in plants, maintaining strict protein
      quality control and degrading specific sets of proteins in response to diverse
      environmental and developmental stimuli. Similarities and differences between the
      proteases expressed in different species may give valuable insights into their
      physiological roles and evolution. RESULTS: We have performed a comparative
      analysis of protease genes in the two sequenced dicot genomes, Arabidopsis
      thaliana and Populus trichocarpa by using genes coding for proteases in the
      MEROPS database 1 for Arabidopsis to identify homologous sequences in Populus. A
      multigene-based phylogenetic analysis was performed. Most protease families were
      found to be larger in Populus than in Arabidopsis, reflecting recent genome
      duplication. Detailed studies on e.g. the DegP, Clp, FtsH, Lon, rhomboid and
      papain-Like protease families showed the pattern of gene family expansion and
      gene loss was complex. We finally show that different Populus tissues express
      unique suites of protease genes and that the mRNA levels of different classes of
      proteases change along a developmental gradient. CONCLUSION: Recent gene family
      expansion and contractions have made the Arabidopsis and Populus complements of
      proteases different and this, together with expression patterns, gives
      indications about the roles of the individual gene products or groups of
      proteases.

PMID- 17181861
TI  - Human antimicrobial peptide LL-37 is present in atherosclerotic plaques and
      induces death of vascular smooth muscle cells: a laboratory study.
AB  - BACKGROUND: Death of smooth muscle cells in the atherosclerotic plaques makes the
      plaques more prone to rupture, which can initiate an acute ischemic event. The
      development of atherosclerosis includes the migration of immune cells e.g.
      monocytes/macrophages and T lymphocytes into the lesions. Immune cells can
      release antimicrobial peptides. One of these, human cathelicidin antimicrobial
      peptide hCAP-18, is cleaved by proteinase 3 generating a 4.5 kDa C-terminal
      fragment named LL-37, which has been shown to be cytotoxic. The aim of the study
      was to explore a potential role of LL-37 in the pathophysiology of
      atherosclerosis. METHODS: We investigated the presence of LL-37 in human
      atherosclerotic lesions obtained at autopsy using immunohistochemistry. The
      direct effects of LL-37 on cultured vascular smooth muscle cells and isolated
      neutrophil granulocytes were investigated with morphological, biochemical and
      flow cytometry analysis. RESULTS: The neointima of atherosclerotic plaques was
      found to contain LL-37-like immunoreactivity, mainly in macrophages. In cultured
      smooth muscle cells, LL-37 at 30 mug/ml caused cell shrinkage, membrane blebbing,
      nuclear condensation, DNA fragmentation and an increase in caspase-3 activity as
      studied by microscopy, ELISA and enzyme activity assay, respectively. Flow
      cytometry demonstrated that LL-37 in a subset of the cells caused a small but
      rapidly developing increase in membrane permeability to propidium iodide,
      followed by a gradual development of FITC-annexin V binding. Another cell
      population stained heavily with both propidium iodide and FITC-annexin V.
      Neutrophil granulocytes were resistant to these effects of LL-37. CONCLUSION:
      This study shows that LL-37 is present in atherosclerotic lesions and that it
      induces death of vascular smooth muscle cells. In a subset of cells, the changes
      indicate the development of apoptosis triggered by an initial mild perturbation
      of plasma membrane integrity. The findings suggest a role for LL-37 as a mediator
      of immune cell-induced death of vascular smooth muscle cells in atherosclerosis.

PMID- 17181863
TI  - Classification methods for the development of genomic signatures from high
      dimensional data.
AB  - Personalized medicine is defined by the use of genomic signatures of patients to
      assign effective therapies. We present Classification by Ensembles from Random
      Partitions (CERP) for class prediction and apply CERP to genomic data on leukemia
      patients and to genomic data with several clinical variables on breast cancer
      patients. CERP performs consistently well compared to the other classification
      algorithms. The predictive accuracy can be improved by adding some relevant
      clinical/histopathological measurements to the genomic data.

PMID- 17181864
TI  - HIV-1 Tat interaction with Dicer: requirement for RNA.
AB  - Dicer is an RNase III which processes two classes of cellular small RNAs: the
      microRNAs (miRNA) and short interfering RNAs (siRNA). Previously, we observed
      that over-expressed HIV-1 Tat protein can suppress the processing of small RNAs
      inside cells. Here, we have investigated the requirements for Tat interaction
      with Dicer. We report that Tat-Dicer interaction depends on RNA, requires the
      helicase domain of Dicer, and is independent of Tat's transactivation domain.

PMID- 17181865
TI  - Is the HIV burden in India being overestimated?
AB  - BACKGROUND: The HIV burden estimate for India has a very wide plausibility range.
      A recent population-based study in a south Indian district demonstrated that the
      official method used in India to estimate HIV burden in the population, which
      directly extrapolates annual sentinel surveillance data from large public sector
      antenatal and sexually transmitted infection (STI) clinics, led to a 2-3 times
      higher estimate than that based on population-based data. METHODS: We assessed
      the generalisability of the reasons found in the Guntur study for overestimation
      of HIV by the official sentinel surveillance based method: addition of
      substantial unnecessary HIV estimates from STI clinics, the common practice of
      referral of HIV positive/suspect patients by private practitioners to public
      hospitals, and a preferential use of public hospitals by lower socioeconomic
      strata. We derived conservative correction factors for the sentinel surveillance
      data and titrated these to the four major HIV states in India (Andhra Pradesh,
      Maharashtra, Karnataka and Tamil Nadu), and examined the impact on the overall
      HIV estimate for India. RESULTS: HIV data from STI clinics are not used elsewhere
      in the world as a component of HIV burden estimation in generalised epidemics,
      and the Guntur study verified that this was unnecessary. The referral of HIV
      positive/suspect patients from the private to the public sector is a widespread
      phenomenon in India, which is likely causing an upward distortion in HIV
      estimates from sentinel surveillance in other parts of India as well. Analysis of
      data from the nationwide Reproductive and Child Health Survey revealed that lower
      socioeconomic strata were over-represented among women seeking antenatal care at
      public hospitals in all major south Indian states, similar to the trend seen in
      the Guntur study. Application of conservative correction factors derived from the
      Guntur study reduced the 2005 official sentinel surveillance based HIV estimate
      of 3.7 million 15-49 years old persons in the four major states to 1.5-2.0
      million, which would drop the official total estimate of 5.2 million 15-49 years
      old persons with HIV in India to 3-3.5 million. CONCLUSION: Plausible and
      cautious extrapolation of the trends seen in a recent large and rigorous
      population-based study of HIV in a south Indian district suggests that India is
      likely grossly overestimating its HIV burden with the current official sentinel
      surveillance based method. This method needs revision.

PMID- 17181866
TI  - Effects of the diabetes linked TCF7L2 polymorphism in a representative older
      population.
AB  - BACKGROUND: A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene has
      been found to be associated with type 2 diabetes in case-control studies. We
      aimed to estimate associations of the marker rs7903146 (C/T) polymorphism with
      fasting glucose, lipids, diabetes prevalence and complications in an older
      general population. METHODS: In total, 944 subjects aged > or = 65 years from the
      population representative InCHIANTI study were enrolled in this study. Those with
      fasting blood glucose of > or = 7 mmol/l or physician diagnosis were considered
      diabetic. Cut-off points for impaired fasting glucose (IFG) were > or = 5.6
      mmol/l to < 7 mmol/l. RESULTS: In the general population sample, minor (T) allele
      carriers of rs7903146 had higher fasting blood glucose (FBG) (p = 0.028) but
      lower fasting insulin (p = 0.030) and HOMA2b scores (p = 0.001), suggesting
      poorer beta-cell function. T allele carriers also had smaller waist circumference
      (p = 0.009), lower triglyceride levels (p = 0.006), and higher high-density
      lipoprotein cholesterol (p = 0.008). The prevalence of diabetes or IFG was 32.4%
      in TT carriers and 23.3% in CC carriers; adjusted OR = 1.67 (95% confidence
      interval 1.05 to 2.65, p = 0.031). Within the diabetic and IFG groups, fewer T
      allele carriers had metabolic syndrome features (p = 0.047) or had experienced a
      myocardial infarction (p = 0.037). Conversely, T allele carriers with diabetes
      had poorer renal function (reduced 24-hour creatinine clearance, p = 0.013), and
      possibly more retinopathy (p = 0.067). Physician-diagnosed dementia was more
      common in the T carriers (in diabetes p = 0.05, with IFG p = 0.024). CONCLUSION:
      The TCF7L2 rs7903146 polymorphism is associated with lower insulin levels,
      smaller waist circumference, and lower risk lipid profiles in the general elderly
      population. Patients with diabetes who are carriers of the minor allele are less
      likely to have metabolic-syndrome features, but may experience more microvascular
      complications, although the number of cases was small. If replicated, these
      findings may have implications for developing treatment approaches tailored by
      genotype.

PMID- 17181867
TI  - Prioritising between direct observation of therapy and case-finding interventions
      for tuberculosis: use of population impact measures.
AB  - BACKGROUND: Population impact measures (PIMs) have been developed as tools to
      help policy-makers with locally relevant decisions over health risks and
      benefits. This involves estimating and prioritizing potential benefits of
      interventions in specific populations. Using tuberculosis (TB) in India as an
      example, we examined the population impact of two interventions: direct
      observation of therapy and increasing case-finding. METHODS: PIMs were calculated
      using published literature and national data for India, and applied to a notional
      population of 100,000 people. Data included the incidence or prevalence of smear
      positive TB and the relative risk reduction from increasing case finding and the
      use of direct observation of therapy (applied to the baseline risks over the next
      year), and the incremental proportion of the population eligible for the proposed
      interventions. RESULTS: In a population of 100,000 people in India, the directly
      observed component of the Directly Observed Treatment, Short-course (DOTS)
      programme may prevent 0.188 deaths from TB in the next year compared with 1.79
      deaths by increasing TB case finding. The costs of direct observation are (in
      international dollars) 5960 I dollars and of case finding are 4839 I dollars or
      31702 I dollars and 2703 I dollars per life saved respectively. CONCLUSION:
      Increasing case-finding for TB will save nearly 10 times more lives than will the
      use of the directly observed component of DOTS in India, at a smaller cost per
      life saved. The demonstration of the population impact, using simple and explicit
      numbers, may be of value to policy-makers as they prioritize interventions for
      their populations.

PMID- 17181868
TI  - Functional status decline as a measure of adverse events in home health care: an
      observational study.
AB  - BACKGROUND: Research that examines the quality of home health care is complex
      because no gold standard exists for measuring adverse outcomes, and because the
      patient and clinician populations are highly heterogeneous. The objectives in
      this study are to develop models to predict functional decline for three indices
      of functional status as measures of adverse events in home health care and
      determine which index is most appropriate for risk-adjusting for future quality
      research. METHODS: Data come from the Outcomes and Assessment Information Set
      (OASIS) from a large urban home health care agency and other agency data.
      Prognostic data yields 49,437 episodes, while follow-up data yields 47,684
      episodes. We tested three indices defined as substantial decline in three or more
      (gt3_ADLs), two or more (gt2_ADLs), and one or more (gt1_ADLs) ADLs. Multivariate
      logistic regression determines the performance of the models for each index as
      measured by the c-statistic and Hosmer-Lemeshow chi square (chi2). RESULTS:
      Frequencies for gt3_ADLs, gt2_ADLs, and gt1_ADLs are 212 (0.43%), 783 (1.58%),
      and 4,271 (8.64%) respectively. Follow-up results are comparable with frequencies
      of 218 (0.46%), 763 (1.60%), and 3,949 (8.28%) for each index. Gt3_ADLs does not
      produce valid models. The model for gt2_ADLs consistently yields a higher c
      statistic compared to gt1_ADLs (0.754 vs. 0.679, respectively). Both indices'
      models yield non-significant Hosmer-Lemeshow chi square indicating reasonable
      model fit. Findings for gt2_ADLs and gt1_ADLs are consistent over time as
      indicated by follow-up data results. CONCLUSION: Gt2_ADLs yields the best models
      as indicated by a high c-statistic and a non-significant Hosmer-Lemeshow chi2,
      both of which exhibit exceptional consistency. We conclude that gt2_ADLs may be
      preferable in defining ADL adverse events in the context of home health care.

PMID- 17181870
TI  - Comparison of tissue pressure and ablation time between the LeVeen and cool-tip
      needle methods.
AB  - BACKGROUND: Radio frequency ablation (RFA) has been accepted clinically as a
      useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic
      recurrence after RFA has been reported which might be attributable to increase in
      intra-tumor pressure during RFA. To reduce the pressure and ablation time, we
      developed a novel method of RFA, a multi-step method in which a LeVeen needle, an
      expansion-type electrode, is incrementally and stepwise expanded. We compared the
      maximal pressure during ablation and the total ablation time among the multi-step
      method, single-step method (a standard single-step full expansion with a LeVeen
      needle), and the method with a cool-tip electrode. Finally, we performed a
      preliminary comparison of the ablation times for these methods in HCC cases.
      RESULTS: A block of pig liver sealed in a rigid plastic case was used as a model
      of an HCC tumor with a capsule. The multi-step method with the LeVeen electrode
      resulted in the lowest pressure as compared with the single-step or cool-tip
      methods. There was no significant difference in the ablation time between the
      multi-step and cool-tip ablation methods, although the single-step methods had
      longer ablation times than the other ablation procedures. In HCC cases, the multi
      step method had a significantly shorter ablation time than the single-step or
      cool-tip methods. CONCLUSION: We demonstrated that the multi-step method was
      useful to reduce the ablation time and to suppress the increase in pressure. The
      multi-step method using a LeVeen needle may be a clinically applicable procedure
      for RFA.

PMID- 17181872
TI  - No effect of increased water intake on blood viscosity and cardiovascular risk
      factors.
AB  - Observational data have suggested that increased water intake decreases the risk
      of CHD. A postulated mechanism is that increased water ingestion reduces blood
      viscosity. The aim of the present study was to assess the effect of increased
      fluid intake on blood viscosity. Men (n 67) and postmenopausal women (n 27) with
      one or more risk factors for CVD who reported intake of < or =0.5 litres water
      daily were randomised to a control group (n 31), an intervention group (n 32)
      that increased their daily water intake by 1 litre/d and an intervention group (n
      31) that ingested 1 litre blueberry juice/d. All were encouraged to continue
      their usual diet and lifestyle. Whole-blood viscosity and blood and urine
      chemistries were measured by standard techniques after 2 and 4 weeks. Urine
      volume increased (by a median of 872 and 725 ml in the water and blueberry juice
      groups, respectively, v. 10 ml in the control group; P< or =0.002), confirming
      the subjects' adherence to the protocol. Urine osmolality and urinary levels of
      Na, K and creatinine decreased in the water and blueberry juice groups v. the
      controls (P<0.05). No change was seen in whole-blood viscosity or in levels of
      fibrinogen, total protein, lipids, glucose, insulin, C-peptide or other chemistry
      and haematology variables. In conclusion, a postulated protective effect of
      increased water or fluid intake is not explained by a change in blood viscosity
      and increased fluid intake does not influence CVD risk factors in the short term.

PMID- 17181869
TI  - Changes in skeletal muscle gene expression following clenbuterol administration.
AB  - BACKGROUND: Beta-adrenergic receptor agonists (BA) induce skeletal muscle
      hypertrophy, yet specific mechanisms that lead to this effect are not well
      understood. The objective of this research was to identify novel genes and
      physiological pathways that potentially facilitate BA induced skeletal muscle
      growth. The Affymetrix platform was utilized to identify gene expression changes
      in mouse skeletal muscle 24 hours and 10 days after administration of the BA
      clenbuterol. RESULTS: Administration of clenbuterol stimulated anabolic activity,
      as indicated by decreased blood urea nitrogen (BUN; P < 0.01) and increased body
      weight gain (P < 0.05) 24 hours or 10 days, respectively, after initiation of
      clenbuterol treatment. A total of 22,605 probesets were evaluated with 52
      probesets defined as differentially expressed based on a false discovery rate of
      10%. Differential mRNA abundance of four of these genes was validated in an
      independent experiment by quantitative PCR. Functional characterization of
      differentially expressed genes revealed several categories that participate in
      biological processes important to skeletal muscle growth, including regulators of
      transcription and translation, mediators of cell-signalling pathways, and genes
      involved in polyamine metabolism. CONCLUSION: Global evaluation of gene
      expression after administration of clenbuterol identified changes in gene
      expression and overrepresented functional categories of genes that may regulate
      BA-induced muscle hypertrophy. Changes in mRNA abundance of multiple genes
      associated with myogenic differentiation may indicate an important effect of BA
      on proliferation, differentiation, and/or recruitment of satellite cells into
      muscle fibers to promote muscle hypertrophy. Increased mRNA abundance of genes
      involved in the initiation of translation suggests that increased levels of
      protein synthesis often associated with BA administration may result from a
      general up-regulation of translational initiators. Additionally, numerous other
      genes and physiological pathways were identified that will be important targets
      for further investigations of the hypertrophic effect of BA on skeletal muscle.

PMID- 17181871
TI  - Chemoresistance induces enhanced adhesion and transendothelial penetration of
      neuroblastoma cells by down-regulating NCAM surface expression.
AB  - BACKGROUND: Drug resistance to chemotherapy is often associated with increased
      malignancy in neuroblastoma (NB). One explanation for the link between resistance
      and malignancy might be that resistance facilitates cancer progression and
      invasion. To investigate this hypothesis, adhesion, transendothelial penetration
      and NCAM (CD56) adhesion receptor expression of drug-resistant versus drug
      sensitive NB tumor cells were evaluated. METHODS: Acquired drug resistance was
      mimicked by exposing parental UKF-NB-2, UKF-NB-3 or IMR-32 tumor cells to
      increasing concentrations of vincristine- (VCR) or doxorubicin (DOX) to establish
      the resistant tumor cell sublines UKF-NB-2VCR, UKF-NB-2DOX, UKF-NB-3VCR, UKF-NB
      3DOX, IMR-32VCR and IMR-32DOX. Additionally, the malignant behaviour of UKF-NB-4,
      which already possessed the intrinsic multidrug resistance (MDR) phenotype, was
      analyzed. UKF-NB-4 exposed to VCR or DOX were designated UKF-NB-4VCR or UKF-NB
      4DOX. Combined phase contrast - reflection interference contrast microscopy was
      used to separately evaluate NB cell adhesion and penetration. NCAM was analyzed
      by flow cytometry, western blot and RT-PCR. RESULTS: VCR and DOX resistant tumor
      sublines showed enhanced adhesion and penetration capacity, compared to their
      drug naive controls. Strongest effects were seen with UKF-NB-2VCR, UKF-NB-3VCR
      and IMR-32DOX. DOX or VCR treatment also evoked increased invasive behaviour of
      UKF-NB-4. The process of accelerated tumor invasion was accompanied by decreased
      NCAM surface and protein expression, and down-regulation of NCAM coding mRNA.
      Transfection of UKF-NB-4VCR cells with NCAM cDNA led to a significant receptor up
      regulation, paralleled by diminished adhesion to an endothelial cell monolayer.
      CONCLUSION: It is concluded that NB cells resistant to anticancer drugs acquire
      increased invasive capacity relative to non-resistant parental cells, and that
      enhanced invasion is caused by strong down-regulation of NCAM adhesion receptors.

PMID- 17181873
TI  - Conventional and real-time polymerase chain reaction assessment of the fate of
      transgenic DNA in sheep fed Roundup Ready rapeseed meal.
AB  - Conventional and real-time PCR were used to detect transgenic DNA in digesta,
      faeces and blood collected from six ruminally and duodenally cannulated sheep fed
      forage-based (F) or concentrate-based (C) diets containing 15% Roundup Ready (RR)
      rapeseed meal (n 3). The sheep were adapted for 14 d to F or C diets containing
      non-GM rapeseed, then fed the RR diets for 11 d. On day 12, they were switched
      back to non-GM diets for a further 11 d. Ruminal and duodenal fluids (RF, DF) and
      faecal samples were collected at 3 or 4 h intervals over the 4 d immediately
      following the last feeding of GM diets. DNA was isolated from whole RF and DF,
      from the cell-free supernatant fraction, and from culture fermentation liquid.
      Blood was collected on days 1, 5 and 9 of feeding the RR rapeseed meal. The 1363
      bp 5-enolpyruvylshikimate-3-phosphate synthase transgene (epsps) was quantifiable
      in whole RF and DF for up to 13 h, and a 108 bp epsps fragment for up to 29 h.
      Transgenic DNA was not detectable in faeces or blood, or in microbial DNA. Diet
      type (F v. C) did not affect (P>0.05) the quantity of transgenic DNA in digesta.
      More (P<0.05) transgenic DNA was detected in RF than in DF, but there was an
      interaction (P<0.05) between sample type and collection time. In supernatant
      fractions from RF and DF, three different fragments of transgenic DNA ranging in
      size from 62 to 420 bp were not amplifiable.

PMID- 17181874
TI  - Palmitic acid increase levels of pancreatic duodenal homeobox-1 and p38/stress
      activated protein kinase in islets from rats maintained on a low protein diet.
AB  - A severe reduction in insulin release in response to glucose is consistently
      noticed in protein-deprived rats and is attributed partly to the chronic exposure
      to elevated levels of NEFA. Since the pancreatic and duodenal transcription
      factor homeobox 1 (PDX-1) is important for the maintenance of beta-cell
      physiology, and since PDX-1 expression is altered in the islets of rats fed a low
      protein (LP) diet and that rats show high NEFA levels, we assessed PDX-1 and
      insulin mRNA expression, as well as PDX-1 and p38/stress activated protein kinase
      2 (SAPK2) protein expression, in islets from young rats fed low (6%) or normal
      (17%; control) protein diets and maintained for 48 h in culture medium containing
      5.6 mmol/l glucose, with or without 0.6 mmol/l palmitic acid. We also measured
      glucose-induced insulin secretion and glucose metabolism. Insulin secretion by
      isolated islets in response to 16.7 mmol/l glucose was reduced in LP compared
      with control rats. In the presence of NEFA, there was an increase in insulin
      secretion in both groups. At 2.8 mmol/l glucose, the metabolism of this sugar was
      reduced in LP islets, regardless of the presence of this fatty acid. However,
      when challenged with 16.7 mmol/l glucose, LP and control islets showed a severe
      reduction in glucose oxidation in the presence of NEFA. The PDX-1 and insulin
      mRNA were significantly higher when NEFA was added to the culture medium in both
      groups of islets. The effect of palmitic acid on PDX-1 and p38/SAPK2 protein
      levels was similar in LP and control islets, but the increase was much more
      evident in LP islets. These results demonstrate the complex interrelationship
      between nutrients in the control of insulin release and support the view that
      fatty acids play an important role in glucose homeostasis by affecting molecular
      mechanisms and stimulus/secretion coupling pathways.

PMID- 17181875
TI  - Genetic and environmental contributions to serum ascorbic acid concentrations:
      the Stanislas Family Study.
AB  - Although numerous environmental factors are documented to influence serum
      ascorbic concentrations, little is known about the genetic versus environmental
      contributions to variation of this trait. The aim of this study was to estimate
      family correlation and, additive genetic heritability and household effects in a
      variance component analysis for serum ascorbic acid concentrations. In a sample
      of ninety French families, information was obtained regarding serum ascorbic acid
      concentrations, usual dietary intake, lifestyle, and other related covariates.
      Spouse, parent-offspring and offspring-offspring significant correlation
      coefficients for serum ascorbic acid concentrations, adjusted for age, cigarette
      consumption and oral contraceptive use, were 0.432, 0.298 and 0.485,
      respectively, and for adjusted values for additional diet covariates (vitamin C
      intake and fruit and vegetable consumption), were 0.362, 0.154 and 0.348,
      respectively. Variance component analysis for serum ascorbic concentrations
      showed no significant genetic contribution to variability of this trait.
      Conversely, household common environment accounted for 27.7 and 42.6% in parents
      and offspring, respectively, after adjustment for age, cigarette consumption and
      oral contraceptive use. After adjustment for the two additional diet covariates
      (vitamin C intake and fruit and vegetable consumption) household common variance
      decreased to 13.6 and 30.5% in parents and offspring, respectively. These results
      show that serum ascorbic acid concentrations aggregate within healthy families
      partly due to diet intake but without a significant genetic component.

PMID- 17181876
TI  - Hypolipidaemic effect of chemically different mucilages in rats: a comparative
      study.
AB  - Different classes of fibres differ in their potential to lower lipid levels. In
      order to examine how chemically diverse fibres differ in their hypolipidaemic
      activity, mucilages of varying chemical composition isolated from three different
      sources were administered to experimental animals and the metabolism of lipids
      and lipoproteins was studied. The mucilages used were a galactomannan isolated
      from fenugreek (Trigonella foenum-graecum) seeds, a glucomannan from Dioscorea
      esculenta tubers and an arabinogalactan from Colocasia esculenta tubers. Rats
      were fed these mucilages at a dose of 4 mg/100 g body weight per d for 8 weeks
      and the changes in the levels of total cholesterol and triacylglycerols in serum,
      liver and aorta were analysed. All these mucilages decreased lipid levels both in
      serum and tissues. Among these mucilages, glucomannan showed the most
      hypolipidaemic effect followed by galactomannan and arabinogalactan. Further,
      hepatocytes were isolated from the livers of mucilage-fed rats and the synthesis
      and secretion of lipoproteins were studied using metabolic labelling. There was a
      decrease in the synthesis and secretion of apoB-containing lipoproteins, mainly
      VLDL, by hepatocytes isolated from mucilage-fed rats when compared to control
      (P<0.05). This was further confirmed by pulse chase analysis. Among the different
      mucilages, mannose-rich glucomannan showed the most effect followed by
      galactomannan, and mannose-free arabinogalactan showed minimal effect. Comparison
      of relative viscosity and water-holding capacity showed that mannan-rich
      mucilages like galactomannan and glucomannan, which showed greater hypolipidaemic
      effect, had greater relative viscosity and water-holding capacity. The present
      results suggested that the hypolipidaemic effect of dietary fibre involves a
      decrease in hepatic production of VLDL and further that it varies with the nature
      of the fibre.

PMID- 17181877
TI  - Long-term consequences of under-nutrition during suckling on glucose tolerance
      and lipoprotein profile in female and male rats.
AB  - To determine the effect of under-nutrition during suckling in adults, at delivery
      female Sprague Dawley rats were allowed to lactate litters of either eight
      (controls) or sixteen pups each (large litter, LL). The amount of milk taken by
      LL pups was less than the controls and the concentration of triacylglycerols (TG)
      in the milk of the former was lower. The increase of both body weight and length
      in LL was lower than in the controls during suckling. At weaning, pups were
      allowed to eat ad libitum a standard diet and whereas at 20 months female body
      weight did not differ between LL and control rats, LL males weighed less than
      controls. Plasma NEFA were lower in male LL than in controls at 10 months, leptin
      at 10 and 16 months and TG and VLDL-TG at 20 months, with no differences in
      females. When 20 months old, lumbar and epididymal adipose tissue weights were
      lower in male LL than in controls, but not in females. The increase in plasma
      insulin after oral glucose load was lower in LL than in controls, both in males
      and females at 4 and 16 months, and only in males at 10 months, whereas the
      change in plasma glucose remained constant between the groups. Results indicate
      that both the pancreatic beta-cell function and insulin sensitivity and adipose
      tissue metabolism are independently programmed as a consequence of under
      nutrition during suckling, the effect being more manifest for males than for
      females.

PMID- 17181878
TI  - Zn-limited diet modifies the expression of the rate-regulatory enzymes involved
      in phosphatidylcholine and cholesterol synthesis.
AB  - Suboptimal intake of Zn is one of the most common nutritional worldwide problems.
      Previously, we showed that Zn deficiency produces alterations in lung lipid
      metabolism in rats. We studied the effect of a Zn-limited (ZL) diet on the
      expression of the enzymes involved in phosphatidylcholine and cholesterol
      synthesis. After 2 months of treatment with a ZL diet we found important
      variations in the lipid content of Wistar male rats: triacylglycerol (TG)
      decreased 60% (P<0.001) while esterified cholesterol (EC), free cholesterol and
      phospholipids (PL) increased 66%, 24 % and 25% respectively. We also observed a
      decrease of 40 % in the amount of (3)H incorporated into TG and an increase of
      47% and 28% in the (3)H incorporated to PL and EC respectively. Fatty acid
      synthase and glucose-6-phosphate dehydrogenase activity was increased (P<0.01 and
      P<0.05 respectively). Glycerol-3-phosphate acyltransferase, lipoprotein lipase,
      diacyl glycerol acyl transferase and 3-hydroxy-3-methylglutaryl CoA reductase
      expression decreased (P<0.01 in all cases), while acetyl CoA carboxylase and
      cholinephosphate cytidylyltransferase increased (P<0.01 and P<0.005
      respectively). These results suggest that ZL alters the expression of enzymes
      involved in phosphatidylcholine and cholesterol synthesis, which could lead to
      increased PL and cholesterol and decreased TG. This study suggests that major
      changes in the lipid composition of lung are induced by a ZL condition.
      Therefore, Zn deficiency must be taken into account in order to design therapies
      and public health interventions, such as Zn supplementation for high-risk
      subjects or certain diseases, such as asthma.

PMID- 17181879
TI  - The fatty acid pattern of dietary fat influences the oral bioavailability of the
      flavonol quercetin in pigs.
AB  - We have shown recently that dietary fat content influences the bioavailability of
      the flavonol quercetin. In the present study, the influence of the fatty acid
      pattern of dietary fats on the oral bioavailability of quercetin was
      investigated. Quercetin (30 micromol/kg body weight) was administered to growing
      pigs (n 6) in test meals consisting either of 200 g of a standard pig diet (2%
      crude fat) or of the same diet supplemented with 15 g fat/100 g diet using either
      medium-chain (MCT) or long-chain fatty acid triacylglycerols (LCT). Blood samples
      were drawn repeatedly over a period of 24 h and analysed by HPLC. In addition,
      the influence of the different diets on gastric emptying was investigated in
      rats. In pigs, the bioavailability of quercetin was measured by quantifying its
      plasma metabolites with an intact flavonol structure. Bioavailability was
      enhanced by 38% (P<0.05) and 12% (P>0.05) after intake with the MCT and LCT
      diets, respectively, compared to the standard diet. Maximum plasma concentrations
      of quercetin were reached significantly later with the MCT diet than with the LCT
      or the standard diet (P<0.05). No differences in dry matter of the gastric
      content were observed 60 min after intake of the experimental diets in rats.
      Thus, administration of quercetin together with a diet containing MCT fat
      enhances the bioavailability of the flavonol. Absorption of quercetin was delayed
      significantly with this diet. However, this was probably not due to slower
      gastric emptying of the MCT diet.

PMID- 17181880
TI  - Serum free testosterone, leptin and soluble leptin receptor changes in a 6-week
      strength-training programme.
AB  - Strength training is usually associated with a reduction in fat mass and with
      muscle hypertrophy. The aim of the present study was to examine whether the serum
      free leptin index (FLI), measured by the molar excess of soluble leptin receptor
      (sOB-R) over leptin, is increased by 6 weeks of strength training. Eighteen male,
      physical education students were randomly assigned to two groups: a strength
      training (n 12) and a control group (n 6). Body composition (lean body mass and
      body fat) determined by dual-energy X-ray absorptiometry (DXA), muscle
      performance and leptin, sOB-R, total testosterone and free testosterone
      concentrations were determined before and after training. Fat mass was reduced by
      1 kg with strength training (P<0.05). Lean body mass of trained extremities was
      increased by 3% (P<0.05), while the concentration of free testosterone in serum
      was reduced by 17% (P<0.05) after training. However, despite the reduction in fat
      mass and free testosterone, serum leptin concentration was not significantly
      affected by strength training, even after accounting for the differences in body
      fat. By contrast, for a given fat mass, the sOB-R was increased by 13% (P<0.05)
      at the end of the strength-training programme, although the molar excess of sOB-R
      over leptin remained unchanged. Therefore, the quantity of free leptin available
      to bind to the target tissues was not significantly affected by the short
      strength-training programme, which elicited a 7% reduction in fat mass.

PMID- 17181881
TI  - Effect of diet composition on pregnancy outcome in overnourished rapidly growing
      adolescent sheep.
AB  - When pregnant adolescent sheep are overnourished to promote maternal growth
      during pregnancy, growth of the placenta is impaired and results in the premature
      delivery of low birth weight lambs relative to control-fed adolescents of
      equivalent age. These effects have been achieved by feeding two levels of the
      same complete diet. The present study evaluated the role of protein in pregnancy
      outcome in our adolescent sheep paradigm. Adolescent ewes were implanted with
      single embryos on day 4 post-oestrus. Thereafter ewes were offered ad libitum an
      isoenergetic diet (11.4 MJ metabolisable energy/kg DM) containing either 12%
      (basic, B) or 17% (extra, E) crude protein. At day 75 of gestation, half the
      pregnant ewes on each protein level were switched to yield four groups, BB, EE,
      BE and EB protein. A further optimally nourished control group received a
      moderate quantity of a ration (14% crude protein) designed to provide 100% of the
      estimated energy and protein requirement of the adolescent sheep according to
      stage of pregnancy. Pregnancy outcome was determined at term. Feed intakes were
      independent of protein level in the four groups of ewes fed ad libitum and were
      higher (P<0.001) than in the control group throughout. Maternal plasma urea
      concentrations reflected the current crude protein content of the diet offered
      and were elevated in the 17% compared with 12% protein groups (P<0.001). Within
      groups fed ad libitum, maternal plasma insulin, glucose, NEFA and homocysteine
      concentrations were largely independent of protein level. Gestation length,
      placental weight, lamb birth weight and initial colostrum yield were reduced
      (P<0.05) in all groups fed ad libitum relative to the optimally nourished control
      group. Similarly, total colostrum IgG, butterfat, lactose and crude protein
      content at parturition were attenuated in the ad libitum compared with the
      control groups. However, within ad libitum groups pregnancy outcome parameters
      were largely unaffected by level or timing of exposure to high protein intakes.
      The data imply that it is high-energy intakes that are the primary cause of
      impaired placental development and adverse pregnancy outcome in rapidly growing
      adolescent sheep.

PMID- 17181882
TI  - Overweight induced by high-fat diet delays rat cutaneous wound healing.
AB  - Prolonged wound healing is a complication that contributes to morbidity and
      mortality. Overweight people regularly undergo surgery and trauma, and often
      develop chronic wounds, but the effects of the adipose tissue excess on cutaneous
      wound healing are not well understood. This study tested the hypothesis that
      overweight induced by a high-fat diet impairs rat cutaneous wound healing. Male
      Wistar rats were fed with either a high-fat or a standard (control) diet. After
      15 weeks, an excisional lesion was done and the animals were killed 21 d later.
      Wound contraction and re-epithelialization, blood pressure, glucose and
      retroperitoneal fat were evaluated. After killing, lesion and adjacent normal
      skin were formol-fixed and paraffin-embedded. Inflammatory infiltrate,
      myofibroblasts, collagen fibres and cellular proliferation were analysed and
      blood vessels were evaluated using stereological methods. There was no difference
      in blood pressure and glucose, but retroperitoneal fat increased in the high-fat
      diet group. Animals fed with the high-fat diet presented delayed wound
      contraction and re-epithelialization. It was found that 21 d after wounding,
      overweight induced by a high-fat diet increased the inflammatory infiltrate and
      delayed myofibroblastic differentiation, collagen deposition, epithelial and
      connective tissue cell proliferation, and angiogenesis. These findings support
      the hypothesis that a high-fat diet exerts negative effects on rat cutaneous
      wound healing, due mainly to the prolongation of the inflammatory phase.

PMID- 17181884
TI  - Influence of Ramadan-type fasting on enzymes of carbohydrate metabolism and brush
      border membrane in small intestine and liver of rat used as a model.
AB  - During Ramadan, Muslims the world over abstain from food and water from dawn to
      sunset for a month. We hypothesised that this unique model of prolonged
      intermittent fasting would result in specific intestinal and liver metabolic
      adaptations and hence alter metabolic activities. The effect of Ramadan-type
      fasting was studied on enzymes of carbohydrate metabolism and the brush border
      membrane of intestine and liver from rat used as a model. Rats were fasted (12 h)
      and then refed (12 h) daily for 30 d, as practised by Muslims during Ramadan.
      Ramadan-type fasting caused a significant decline in serum glucose, cholesterol
      and lactate dehydrogenase activity, whereas inorganic phosphate increased but
      blood urea N was not changed. Fasting resulted in increased activities of
      intestinal lactate (+34%), isocitrate (+63%), succinate (+83%) and malate (+106%)
      dehydrogenases, fructose 1,6-bisphosphatase (+17%) and glucose-6-phosphatase
      (+22%). Liver lactate dehydrogenase, malate dehydrogenase, glucose-6-phosphatase
      and fructose 1,6-bisphosphatase activities were also enhanced. However, the
      activities of glucose-6-phosphate dehydrogenase and malic enzyme fell
      significantly in the intestine but increased in liver. Although the activities of
      alkaline phosphatase, gamma-glutamyl transpeptidase and sucrase decreased in
      mucosal homogenates and brush border membrane, those of liver alkaline
      phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase
      significantly increased. These changes were due to a respective decrease and
      increase of the maximal velocities of the enzyme reactions. Ramadan-type fasting
      caused similar effects whether the rats fasted with a daytime or night-time
      feeding schedule. The present results show a tremendous adaptation capacity of
      both liver and intestinal metabolic activities with Ramadan-type fasting in rats
      used as a model for Ramadan fasting in people.

PMID- 17181883
TI  - The influence of inulin on the absorption of nitrogen and the production of
      metabolites of protein fermentation in the colon.
AB  - In the present study, the production and fate of bacterial metabolites in the
      colon were investigated in a direct way using two substrates labelled with stable
      isotopes: lactose [(15)N,(15)N]ureide as a source of labelled ammonia and egg
      proteins intrinsically labelled with [(2)H4]tyrosine as a precursor of [(2)H4]p
      cresol. Both ammonia and phenolic compounds are believed to be carcinogenic.
      Stimulation of carbohydrate fermentation in order to prevent accumulation of
      these toxic metabolites was induced by inclusion of inulin in a test meal or by
      addition of inulin to the daily diet, allowing us to distinguish between changes
      induced by the actual presence of a fermentable carbohydrate and effects caused
      by a long-term dietary intervention. When a single dose of inulin was
      administered together with the labelled substrates, a significant increase in
      faecal (15)N excretion, accompanied by a proportional decrease in urinary (15)N
      excretion was observed, probably reflecting an enhanced uptake of ammonia for
      bacterial biosynthesis, since an increased concentration of labelled N in
      bacterial pellets was found. A statistically significant reduction of urinary
      [(2)H4]p-cresol excretion was also noted. Upon supplementation of inulin to the
      daily diet during 4 weeks, however, only a tendency towards decreased urinary
      excretion of both labelled and unlabelled p-cresol was noted. Further studies are
      warranted to confirm these results in a larger cohort.

PMID- 17181885
TI  - Impact of dietary counselling on nutrient intake during pregnancy: a prospective
      cohort study.
AB  - The aim of this study was to assess the impact of dietary counselling combined
      with the provision of food products on food and nutrient intake in pregnant
      women. We carried out a prospective cohort study of healthy and atopic pregnant
      women (n 209), who were randomized into dietary intervention and control groups.
      The intervention group received dietary counselling and food products to modify
      the fat composition of their diet to meet current recommendations. Three-day food
      records were collected during each trimester of pregnancy. Women in the
      intervention group consumed more vegetables, fruits, soft margarines and
      vegetable oils and less butter than those in the control group during the course
      of pregnancy (P<0.05). The main distinction between the groups in nutrient intake
      over the pregnancy was attributable to a higher energy intake (% energy) of PUFA
      by 0.5%energy (95% CI 0.1, 0.8) and to a lower intake of SFA by 0.8 % energy (95%
      CI -1.4, -0.4) in the intervention group. Dietary intake of vitamin E was 1.4 mg
      (95% CI 0.6, 2.2), folate 20.9 microg (95% CI 0.8, 41.0) and ascorbic acid 19.8
      mg (95 % CI 3.5, 36.0) higher in the intervention group compared to the controls,
      while no differences in other nutrients were detected. Dietary counselling
      combined with the provision of food products during pregnancy is of importance in
      modifying food and nutrient intake, with potential health benefits.

PMID- 17181886
TI  - Comparative dietary intake and sources of phylloquinone (vitamin K1) among
      British adults in 1986-7 and 2000-1.
AB  - Using data from 7 d weighed dietary records, dietary intake and sources of
      phylloquinone (vitamin K1) were examined by socio-demographic and lifestyle
      factors in 1916 participants aged 16-64 years from the 1986-7 Dietary and
      Nutritional Survey of British Adults, and 1423 participants aged 19-64 years from
      the 2000-1 National Diet and Nutrition Survey. Using UK-specific food content
      data, geometric mean phylloquinone intakes were estimated as 72 (95% CI 70, 74)
      and 67 (95% CI 65, 69) microg/d in 1986-7 and 2000-1 respectively (P<0.001). In
      1986-7, 47% of participants had phylloquinone intakes below the UK guideline for
      adequacy (> or =1 microg/kg body weight per d), compared with 59% in 2000-1
      (P<0.001). In both surveys, daily phylloquinone intake was higher among men than
      women and increased significantly with age. Participants of manual occupational
      social class, or who were smokers, had lower phylloquinone intake than their
      counterparts. Participants living in Scotland and northern England had lower
      phylloquinone intake than those living elsewhere in mainland Britain,
      particularly in 1986-7 when the contribution from vegetables was also lower than
      elsewhere. However, by 2000-1 this regional difference was no longer significant.
      Overall, vegetables contributed 63% of phylloquinone intake in 1986-7 and 60% in
      2000-1, with cooked leafy green vegetables (LGV) providing 23 and 19%
      respectively. In both surveys, the contribution of vegetables (cooked LGV in
      particular) was directly associated with age. These data show a decrease in
      phylloquinone intake from 1986-7 to 2000-1, mainly owing to lower consumption of
      cooked LGV.

PMID- 17181888
TI  - Anthocyanin-rich purple potato flake extract has antioxidant capacity and
      improves antioxidant potential in rats.
AB  - Anthocyanins from various vegetables and fruits have antioxidant activities,
      however, the bioactivities of coloured potato anthocyanins are not well studied.
      We examined the antioxidant capacities of pigmented fractions from purple potato
      flakes in vitro, and the antioxidant potentials of purple potato flakes in vivo.
      1,1-Diphenyl-2-picrylhydrazyl radical scavenging activity of the pigmented
      fraction from Hokkai no. 92 (H92) potato flakes was higher than that from
      Kitamurasaki (KM) potato flakes. Extracts equivalent to 600 microg pigmented
      fractions from KM and H92 potato flakes inhibited linoleic acid oxidation in the
      order trolox>H92> or =KM>control. Rats were fed 25% KM or H92 potato flake diets
      for 4 weeks. The major anthocyanin was identified as petanin. Control rats were
      fed a diet with cornstarch instead of potato flakes for 4 weeks. The serum
      antioxidant potential level in the H92 group was significantly higher than that
      in the control group. The degree of hepatic lipid peroxidation in the H92 group
      was significantly lower than that in the control group. Hepatic Cu/Zn-superoxide
      dismutase (SOD), Mn-SOD and glutathione peroxidase (GSH-Px) mRNA levels in the
      H92 group were significantly higher than those in the control group. Similar
      significant differences in Cu/Zn-SOD and Mn-SOD mRNA levels between the KM and
      control groups were found. The present results suggest that purple potato flakes
      have antioxidant functions with regard to radical scavenging activity and
      inhibition of linoleic acid oxidation, and that they improve the antioxidant
      potentials in rats by enhancing hepatic Mn-SOD, Cu/Zn-SOD and GSH-Px mRNA
      expression.

PMID- 17181887
TI  - Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in
      British adults aged 19-64 years.
AB  - Plasma phylloquinone (vitamin K1) concentration from non-fasted blood samples was
      examined by season, smoking status, socio-demographic factors and phylloquinone
      intake in a nationally representative sample of 1154 British individuals aged 19
      64 years from the 2000-1 National Diet and Nutrition Survey. Geometric mean
      plasma phylloquinone concentration was 0.94 (95% CI 0.88, 1.00) nmol/l, with 95%
      of values in the range 0.10-8.72 nmol/l. Plasma phylloquinone concentrations of
      530 men were significantly higher than those of 624 women (1.13 (95% CI 1.04,
      1.22) v. 0.81 (95% CI 0.74, 0.88) nmol/l; P<0.001), independent of other factors.
      Women aged 19-34 years had significantly lower plasma phylloquinone concentration
      than their older counterparts. Women were also found to have lower plasma
      phylloquinone concentrations during summer compared with winter and spring (each
      P<0.01). In contrast, plasma phylloquinone concentration in men did not vary
      significantly by season or any of the socio-demographic or lifestyle factors.
      Plasma phylloquinone concentrations were positively correlated with phylloquinone
      intake in men and women (r 0.26 and 0.32 respectively; each P<0.001). Overall,
      forward stepwise multiple regression analysis revealed that 8% of the variation
      in plasma phylloquinone concentration was explained by phylloquinone intake, with
      a further 10% of its variation explained by plasma concentrations of gamma
      tocopherol (6%) and retinyl palmitate (4%). After adjustment for age and
      corresponding nutrient intakes, plasma phylloquinone concentration was
      significantly associated (each P<0.01) with plasma concentrations of total and
      LDL-cholesterol, alpha- and gamma-tocopherols, retinyl palmitate, beta-carotene,
      lycopene and lutein plus zeaxanthin in men and women.

PMID- 17181889
TI  - Levels of serum transferrin receptor and its response to Fe-supplement in Fe
      deficient children.
AB  - The object of the present study was to investigate the levels of serum
      transferrin receptor (sTfR) and its response to Fe supplementation in Fe
      deficient children and the role of sTfR in detecting Fe deficiency and assessing
      the efficacy of Fe supplementation. According to the diagnostic standard, 1006
      children, aged 6-14 years in Fangshan district, Beijing, Peoples Republic of
      China, were divided into four groups: normal; Fe store depletion (IDs); Fe
      deficiency erythropoiesis (IDE); Fe deficiency anaemia (IDA). sTfR was determined
      and transferrin receptor-ferritin (TfR-F) index was calculated in 238 children,
      sixty-four normal and 174 Fe deficient. Children were administered a NaFeEDTA
      capsule containing 60 mg Fe once per week for the IDs and IDE groups and three
      times per week for the IDA group for nine consecutive weeks. The parameters
      reflecting Fe status and sTfR were determined before and after Fe
      supplementation. The levels of sTfR and TfR-F index in Fe-deficient children were
      significantly higher than those in the normal group. The receiver operating
      characteristic curve showed that sTfR has proper diagnostic efficacy for
      functional Fe deficiency. After Fe supplementation, the level of sTfR was
      significantly decreased in children with IDs, but not in children with IDE and
      IDA, while TfR-F index was significantly decreased in Fe-deficient children. sTfR
      is a reliable indicator for detecting functional Fe deficiency, and TfR-F index
      is a sensitive parameter for assessing the efficacy of Fe supplementation.

PMID- 17181890
TI  - Skeletal site-dependent response of bone mineral density and quantitative
      ultrasound parameters following a 12-month dietary intervention using dairy
      products fortified with calcium and vitamin D: the Postmenopausal Health Study.
AB  - The aim of the current study was to examine whether calcium supplementation could
      prevent bone loss in postmenopausal women or more favourable outcomes could be
      obtained via the consumption of dairy products fortified with calcium and vitamin
      D3. For this purpose changes in bone mineral density (BMD) at different skeletal
      sites, assessed by dual-energy X-ray absorptiometry, as well as in quantitative
      ultrasound (QUS) parameters of the calcaneus over 12 months were estimated. A
      population of 101 postmenopausal women (55-65 years old) was randomized into a
      dairy group (DG: n 39), receiving approximately 1200 mg calcium/d and 7.5 microg
      vitamin D3/d through fortified dairy products; a calcium-supplemented group (CaG:
      n 26) provided with a calcium supplement of 600 mg/d; and a control group (CG: n
      36). Over the intervention period the DG was found to have more favourable
      changes in pelvis (P=0.040), total spine (P<0.001) and total body BMD (P<0.001)
      than the other groups. A significant increase was also observed for DG in lumbar
      spine BMD (2.0%; 95% CI 0.5, 3.5) although it did not differentiate significantly
      compared to the other groups. No significant differences were observed with
      respect to the changes in QUS parameters. The current study revealed that
      recommended intakes of vitamin D3 and calcium via fortified dairy products for 12
      months can induce favourable changes in pelvis, total spine and total body BMD in
      postmenopausal women but not in QUS parameters. No such favourable changes were
      observed via supplementation of calcium alone.

PMID- 17181891
TI  - Parental feeding style, energy intake and weight status in young Scottish
      children.
AB  - Parental feeding style, as measured by the Child Feeding Questionnaire (CFQ), may
      be an important influence on child feeding behaviour and weight status in early
      to mid childhood, but more evidence on parental feeding style is required from
      samples outside the USA. We aimed to use the CFQ in a sample of 117 Scottish
      children (boys n 53, girls n 64 mean age 4.6 (SD 0.5) years) to: characterise
      gender differences and changes over time (in forty of the 117 children studied
      over 2 years); test associations between parental feeding style, free-living
      energy intake (measured over 3 days using the multiple pass 24-h recall), and
      weight status (BMI SD score). No dimensions of parental feeding style changed
      significantly over 2 years in the longitudinal study (P>0.05 in all cases). No
      aspects of parental feeding style as measured by the CFQ differed significantly
      between the sexes (P>0.05 in all cases). Parental perceptions of child weight
      status were generally significantly positively correlated with child weight
      status as measured by the BMI SD score. In this sample and setting, measures of
      parental control over child feeding were generally not associated with child
      energy intake or weight status.

PMID- 17181892
TI  - Perceived body size and desire for thinness of young Japanese women: a population
      based survey.
AB  - The present study describes findings in relation to perceived body size and
      'desire for thinness' by age and residential areas ('metropolitan areas', 'large
      cities', 'small cities' and 'towns') among young Japanese women. Data on 1731 non
      pregnant, non-lactating women aged 15-39 years from the 1998 National Nutrition
      Survey of Japan were used. Current body size was evaluated by BMI percentiles
      (lean, <5th; underweight, 5th or = BMI <25th; normal, 25th< or = BMI< 75th;
      overweight, 75th < or =BMI <95th; obese, > or =95th), calculated for 5-year age
      groups. Perceived body size was obtained by self-report. We defined
      'overestimation' as non-overweight, non-obese women who perceived themselves as
      being 'overweight' or 'obese'. Desired body size was evaluated by applying the
      desired BMI to these cut-off points. Of all the women, 48.4% perceived themselves
      as being 'overweight' or 'obese', and 43.7% desired a 'lean' or 'underweight'
      body size. Adjusted for the current BMI, the OR for 'overestimation' calculated
      by a logistic regression model was significantly elevated in the 15-19-year age
      group (OR 2.79; 95% CI 1.76, 4.43), compared with the 25-29-year age group. The
      OR for 'desire for thinness' was significantly high in the 35-39-year age group
      (OR 2.74; 95% CI 1.93, 3.89) and the 15-19-year age group (OR 2.26; 95% CI 1.57,
      3.24). Women living in metropolitan areas had higher OR for 'desire for thinness'
      (but not for 'overestimation') than did women in towns (OR 1.47; 95% CI 1.05,
      2.07). The findings suggest the nature of excessive weight concerns of young
      women in Japan; thus efforts to control such health-risk behaviours at a national
      level are urgent.

PMID- 17181893
TI  - Validation of foot-to-foot bioelectrical impedance analysis with dual-energy X
      ray absorptiometry in the assessment of body composition in young children: the
      EarlyBird cohort.
AB  - Foot-to-foot bioelectrical impedance analysis (BIA) is simple and non-invasive,
      making it particularly suitable for use in children. There is insufficient
      evidence of the validity of foot-to-foot BIA compared with dual-energy X-ray
      absorptiometry (DEXA) as the criterion method in healthy young children. Our
      objective was to assess the validity of foot-to-foot BIA against DEXA in a large
      cohort of healthy young children. Body composition was measured by foot-to-foot
      BIA and DEXA in 203 children (mean age 8.9 (SD 0.3) years). Bland-Altman and
      simple linear regression analyses were used to determine agreement between
      methods. BIA overestimated fat-free mass by a mean of 2.4% in boys and 5.7% in
      girls, while fat mass was underestimated by 6.5% in boys and 10.3% in girls. The
      percentage fat recorded by BIA was, accordingly, also lower than by DEXA (boys
      4.8%; girls 12.8%). In boys, however, there were correlations between the size of
      the difference between methods and the size of the measure under consideration
      such that in smaller boys fat-free mass was underestimated (r-0.57; P<0.001)
      while fat mass and percentage fat were overestimated (r 0.74 for fat mass; r 0.69
      for percentage fat; both P<0.001) with the reverse in bigger boys. Mean
      differences between techniques were greater in the girls than in the boys but in
      boys only, the direction of the differences was dependent upon the size of the
      child. Therefore, BIA may be useful for large-scale studies but is not
      interchangeable with DEXA and should be interpreted with caution in individuals.

PMID- 17181894
TI  - Fatal flaw in the fetal argument.

PMID- 17181896
TI  - Adequacy of exclusive breast-feeding in 6-month-old infants.

PMID- 17181900
TI  - The Sir David Cuthbertson Medal Lecture. Hunting for new pieces to the complex
      puzzle of obesity.
AB  - Disentangling the neuroendocrine systems that regulate energy homeostasis and
      adiposity has been a long-standing challenge in pathophysiology, with obesity
      being an increasingly important public health problem. Adipose tissue is no
      longer considered a passive bystander in body-weight regulation. It actively
      secretes a large number of hormones, growth factors, enzymes, cytokines,
      complement factors and matrix proteins, at the same time as expressing receptors
      for most of these elements, which influence fuel storage, mobilisation and
      utilisation at both central and peripheral sites. Thus, an extensive cross talk
      at a local and systemic level in response to specific external stimuli or
      metabolic changes underpins the multifunctional characteristics of adipose
      tissue. In addition to the already-known adipokines, such as IL, TNFalpha,
      leptin, resistin and adiponectin, more recently attention has been devoted to
      'newcomers' to the 'adipose tissue arena', which include aquaporin, caveolin,
      visfatin, serum amyloid A and vascular endothelial growth factor. While in vitro
      and in vivo experiments have provided extremely valuable information, the
      advances in genomics, proteomics and metabolomics are offering a level of
      information not previously attainable to help unlock the molecular basis of
      obesity. The potential and power of combining pathophysiological observations
      with the wealth of information provided by the human genome, knock-out models,
      transgenesis, DNA microarrays, RNA silencing and other emerging technologies
      offer a new and unprecedented view of a complex disease, conferring novel
      insights into old questions by identifying new pieces to the unfinished jigsaw
      puzzle of obesity.

PMID- 17181902
TI  - Dietary influences on cognitive development and behaviour in children.
AB  - There are a number of ways in which food can influence behaviour, including
      malnutrition, types of diet, eating habits, pharmacological effects, food
      allergy, fatty acid deficiency and possibly food additives. The range of
      behaviour affected is also wide, and includes attention, conduct disorder and
      mood. A particular focus of interest has been the effects of food on
      hyperactivity in children. There is some initial evidence that fatty acids may
      influence hyperactivity in children with specific learning disabilities. The
      findings also suggest that some food additives (colourings, flavourings and
      preservatives) may increase hyperactivity in children with behaviour problems.
      For children showing behaviour problems such as hyperactivity the use of dietary
      manipulation tends to be a more acceptable approach to treatment than the use of
      drugs. However, there needs to be awareness of the dangers of the use of
      unsupervised restriction diets with children, and the use of dietary treatments
      alone is not likely to be sufficient treatment for many children with attention
      deficit hyperactivity disorder. A study is currently underway to investigate the
      possible effects of additives on behaviour in the general population of children.

PMID- 17181903
TI  - Dietary quality and adequacy of micronutrient intakes in children.
AB  - Presented are longitudinal studies, extending from infancy (n 180) to 2 years of
      age (n 130) and 6 years of age (>70% participation) of diet and Fe status in a
      population with high birth weight, high frequency of breast-feeding and, at the
      time of the study, high intake of cow's milk during the weaning period. The
      association between socio-demographic and dietary factors was also studied,
      together with Fe status in early childhood and developmental status at 6 years.
      Fe status was found to be poorer than in the neighbouring Nordic countries. Every
      fifth 1-year-old was Fe-deficient (serum ferritin <12 microg/l and mean
      corpuscular volume <74 fl). It was demonstrated by regression analysis that Fe
      status was negatively associated with cow's milk consumption at 9-12 months
      (significant at >460 g/d) and was weakly positively associated with fish, meat
      and Fe-fortified cereal consumption. Fe-deficient infants had a shorter duration
      of breast-feeding, and breast-feeding was related to slower growth, which can
      protect from worsening Fe status. Fe deficiency was less common at ages 2 and 6
      years. Maternal factors associated with lower adherence to the recommended infant
      diet were less education, lower age and smoking. In a multiple stepwise
      regression analysis that included food factors, socio-demographic factors were
      not found to be associated with Fe status. Fe-depleted and Fe-deficient 1-year
      olds had lower fine motor scores when they were 6 years old than those who were
      not Fe-deficient or Fe-depleted. The findings of these studies have already led
      to changes in the local recommendations for diet in infancy. The results suggest
      that Fe deficiency at 12 months of age affects development at 6 years of age. The
      studies indicated that mothers with less education, who smoked and who were
      younger needed more guidance concerning recommendations about diet in infancy.

PMID- 17181901
TI  - Nutrition and bone growth and development.
AB  - The growth and development of the human skeleton requires an adequate supply of
      many different nutritional factors. Classical nutrient deficiencies are
      associated with stunting (e.g. energy, protein, Zn), rickets (e.g. vitamin D) and
      other bone abnormalities (e.g. Cu, Zn, vitamin C). In recent years there has been
      interest in the role nutrition may play in bone growth at intakes above those
      required to prevent classical deficiencies, particularly in relation to
      optimising peak bone mass and minimising osteoporosis risk. There is evidence to
      suggest that peak bone mass and later fracture risk are influenced by the pattern
      of growth in childhood and by nutritional exposures in utero, in infancy and
      during childhood and adolescence. Of the individual nutrients, particular
      attention has been paid to Ca, vitamin D, protein and P. There has also been
      interest in several food groups, particularly dairy products, fruit and
      vegetables and foods contributing to acid-base balance. However, it is not
      possible at the present time to define dietary reference values using bone health
      as a criterion, and the question of what type of diet constitutes the best
      support for optimal bone growth and development remains open. Prudent
      recommendations (Department of Health, 1998; World Health Organization/Food and
      Agriculture Organization, 2003) are the same as those for adults, i.e. to consume
      a Ca intake close to the reference nutrient intake, optimise vitamin D status
      through adequate summer sunshine exposure (and diet supplementation where
      appropriate), be physically active, have a body weight in the healthy range,
      restrict salt intake and consume plenty of fruit and vegetables.

PMID- 17181904
TI  - Motivation for eating behaviour in adolescent girls: the body beautiful.
AB  - Body dissatisfaction is commonplace for teenage girls and is associated with
      dieting and unhealthy weight-control behaviours. The idealisation and pursuit of
      thinness are seen as the main drivers of body dissatisfaction, with the media
      prominent in setting thin body ideals. Television and consumer magazine
      production in the UK are extensive, annually releasing 1x10(6) h programming and
      >3000 magazine titles. Their engagement by adolescent girls is high, and in
      surveys girls identify thin and revealing body images as influential to the
      appeal of thinness and their pursuit of dieting. Experimental studies show a
      short-term impact of these images on body dissatisfaction, especially in
      teenagers who are already concerned about body image. Magazine images appear more
      influential than television viewing. For many adolescents selecting thin-image
      media is purposive, permitting comparison of themselves with the models or
      celebrities featured. Indeed, the impact of the media needs to be understood
      within a social context, as engagement is often a highly-social process. Media
      influence is uneven because of differences in its content and manner of
      communication, and individual differences in vulnerability to its content.
      Greater social responsibility on the part of the media and better media literacy
      by children would be beneficial. For those working in adolescent nutrition it is
      a reminder that adolescent food choice and intake are subject to many competing,
      contradictory and non-health-related determinants.

PMID- 17181905
TI  - Body fat measurements in children as predictors for the metabolic syndrome: focus
      on waist circumference.
AB  - The global epidemic of obesity in children will see a rise in the number of cases
      of metabolic syndrome, which is a clustering of CVD risk factors, including
      atherogenic levels of blood lipids, hyperinsulinaemia and raised blood pressure.
      Rather than excess general fatness (assessed by BMI), more specifically it is
      excess abdominal fatness, quantified by waist circumference measurement, which is
      a better measure of risk for these metabolic abnormalities in children of all
      ages. Insulin resistance, a consequence of excess visceral fat, is understood to
      be the driving force underpinning the metabolic syndrome. Consequently,
      assessment of abdominal fatness in children is proving to be more clinically
      useful. Waist circumference centile charts have now been developed for the UK and
      other paediatric populations to assist in this process. Furthermore, studies in
      the UK and elsewhere have shown that abdominal fatness has increased in infants,
      children and adolescents to a greater extent than overall fatness over the past
      10-20 years, suggesting that obesity prevalence may be underestimated when based
      entirely on BMI. Additionally, ethnic differences in fat distribution have been
      demonstrated in children, with those from south Asian backgrounds having a
      greater abdominal distribution compared with Caucasian children and consequently
      having a much greater risk for type 2 diabetes. The information that can be
      provided by waist circumference measurement in children, as in adults, together
      with the recent changes in body fat distribution should provide the impetus for
      its measurement to be standardised and routinely taken in clinical and
      epidemiological settings.

PMID- 17181906
TI  - The effect of physical activity on body fatness in children and adolescents.
AB  - With the increasing prevalence of childhood obesity, there is an urgent need to
      identify risk factors that are amenable to preventative action. However, there is
      a remarkable lack of consistency between studies that have investigated the
      relationships between measurements of physical activity and energy expenditure
      and body fatness in children. This disparity could be because energy intake is a
      more important determinant in preventing obesity. Alternatively, some of the
      conflicting results could be related to methodological limitations in assessing
      activity and body composition. Erroneous conclusions may be drawn if physical
      activity energy expenditure is not adjusted for differences in body composition,
      or body fat is not appropriately adjusted for body size. For public health
      purposes it may be more informative to evaluate the amount and intensity of
      physical activity required to prevent fat-mass gain than to assess energy
      expended in physical activity. The lack of consensus in the cut-off points
      applied to define intensity levels is severely hindering comparisons between
      studies using accelerometers that have examined relationships between activity
      intensity and body fatness. Thus, it is not currently possible to develop a firm
      evidence base on which to establish physical activity recommendations until the
      limitations are addressed and more prospective studies undertaken. In order to
      turn research into effective prevention strategies a clearer understanding of the
      psycho-social, behavioural and environmental factors that influence activity is
      needed, including the interactions between physical activity and other behaviours
      such as time spent sedentary, sleeping and eating.

PMID- 17181907
TI  - Methods of defining best practice for population health approaches with obesity
      prevention as an example.
AB  - Childhood obesity has reached a crisis stage and has become a population health
      issue. The few traditional systematic reviews that have been done to identify
      best practice provide little direction for action. The concept of evidence-based
      practice has been adopted in health care, and in medicine in particular, to
      determine best practice. Evidence-based medicine has its origins in the
      scientific method and for many researchers this concept means strict adherence to
      standards determining internal validity in order to justify a practice as
      evidence based. Practitioners addressing population health face challenges in
      identifying criteria for determining evidence, in part because of the nature of
      population health with its goal of shifting the health of whole populations. As
      well, the type of evidence provided by more traditional critical appraisal schema
      is limiting. Expanded approaches in finding and defining evidence have been
      proposed that use: expert panels; broad and inclusive search and selection
      strategies; appraisal criteria that incorporate context and generalizability. A
      recent synthesis of 147 programmes addressing childhood overweight and obesity
      provides a concrete example of using a broader approach to identify evidence for
      best practice (Flynn et al. 2006). Incorporating evaluation and population health
      frameworks as criterion components in addition to traditional methodological
      rigour criteria, this synthesis has identified programmes that provide contextual
      information that can be used to populate what Swinburn et al. (2005) have
      described as the 'promise table'. Using this approach a range in 'certainty of
      effectiveness' and a range in 'potential for population impact' are integrated to
      identify promising strategies. The exercise can provide direction for agencies
      and practitioners in taking action to address obesity.

PMID- 17181908
TI  - Dietary management of food allergy in children.
AB  - Currently, the only treatment for any food hypersensitivity (including food
      allergy) is the dietary avoidance of the causative allergen, using an elimination
      diet. In addition to being used for the management of food hypersensitivity, an
      elimination diet may also be used in the diagnosis of food allergy. Dietary
      exclusion should be managed by a dietitian or other health professional with
      nutritional expertise to ensure that the exclusion does not lead to a
      nutritionally-deficient diet. There are three main types of elimination diets:
      single-food exclusion; multiple-food exclusion; the 'few-food' diet, which
      requires the avoidance of a large number of allergens and therefore concentrates
      on the foods that can be included rather than the foods that need to be avoided.
      Any sort of elimination diet is hard to manage. Thus, as well as ensuring that
      the diet is nutritionally adequate, it is essential that families are given
      advice and support relevant to their circumstances to aid them in the day-to-day
      management of the diet, so that it remains varied and enjoyable for food-allergy
      sufferers. This approach involves advice about which alternative foods are
      available, provision of 'free-from' recipes and guidance on which nutritional
      supplements are needed to meet their nutritional needs.

PMID- 17181909
TI  - Sustainability in local public health nutrition programmes: beyond nutrition
      education, towards community collaboration.
AB  - The present paper presents the approach, results and outcome of an innovative
      piece of action research amongst professionals (health and non-health) and the
      public (women and young people from low-income families in one of the deprived
      areas of Birmingham, UK). A cooperative inquiry approach was used and data were
      collected on concerns about health of professionals (n 15) and the public (n 19),
      as well as dietary practices, smoking pattern and access to healthy foods amongst
      the public (n 49). The methods of data collection were: desk research;
      observation; semi-structured individual and focus-group interviews; structured
      individual interviews. The findings highlight diverse views and expectations
      about health amongst the public and the professionals, and suggest the existence
      of tensions between the partnership and the ownership of inter-agency
      collaboration. It argues the importance of having a shared vision amongst health
      and non-health professionals regarding health strategy and the way forward for
      working together to promote the public's health. It recommends that by using the
      tenet of action research, and adapting a cooperative inquiry approach, members of
      a partnership project could learn through reflection on action and achieve
      personal development and social action.

PMID- 17181910
TI  - Getting quality in qualitative research: a short introduction to feminist
      methodology and methods.
AB  - The present paper reflects a practical activity undertaken by the Nutrition
      Society's qualitative research network in October 2005. It reflects the structure
      of that exercise. First, there is an introduction to feminist methodology and
      methods. The informing premise is that feminist methodology is of particular
      interest to practitioners (professional and/or academic) engaged in occupations
      numerically dominated by women, such as nutritionists. A critical argument is
      made for a place for feminist methodology in related areas of social research.
      The discussion points to the differences that exist between various feminist
      commentators, although the central aims of feminist research are broadly shared.
      The paper comprises an overview of organizing concepts, discussion and questions
      posed to stimulate discussion on the design and process of research informed by
      feminist methodology. Issues arising from that discussion are summarized.

PMID- 17181911
TI  - Effects of n-3 fatty acids on cartilage metabolism.

PMID- 17181912
TI  - Cognitive functioning in patients with familial bipolar I disorder and their
      unaffected relatives.
AB  - BACKGROUND: Impairments in verbal learning and memory, executive functions and
      attention are manifest in some euthymic patients with bipolar disorder (BPD).
      However, evidence is sparse on their putative role as aetiologically important
      genetic vulnerability markers for the disorder. This population-based study
      examined the cognitive functions of affected and unaffected individuals in
      families with BPD. The aim was to discover whether any cognitive function would
      indicate genetic liability to the disorder and could thus be regarded as
      endophenotypes of BPD. METHOD: A diagnostic interview and a neuropsychological
      test battery were administered to 32 familial bipolar I disorder patients, 40 of
      their unaffected first-degree relatives and 55 controls, all representing
      population-based samples. RESULTS: Unaffected first-degree relatives showed
      impairment in psychomotor performance speed and slight impairment in executive
      function. Bipolar patients were impaired in verbal learning and memory compared
      with unaffected relatives and controls. They also differed from controls in tasks
      of executive functions. There were no difference between the groups in simple
      attention and working memory tasks. CONCLUSIONS: Impaired psychomotor performance
      speed and executive function may represent endophenotypes of BPD, reflecting
      possible underlying vulnerability to the disorder. Verbal memory impairments
      appear to be more related to the fully developed disorder.

PMID- 17181913
TI  - Smoking behaviour as a predictor of depression among Finnish men and women: a
      prospective cohort study of adult twins.
AB  - BACKGROUND: Depression is associated with smoking, but the causality of the
      relationship is debated. The authors examine smoking behaviour as a predictor of
      depression among the Finnish adult twin population. METHOD: Based on responses to
      surveys in 1975 and 1981, the authors characterized the subjects as never
      smokers, persistent former smokers, quitters, recurrent smokers and persistent
      smokers. The Beck Depression Inventory (BDI) was applied in 1990 to measure
      depression (BDI score >9). Although the population consisted of twins, the
      authors first considered the subjects as individuals. Logistic regression models
      were computed for 4164 men and 4934 women. In order to control for family and
      genetic background, conditional logistic regression analyses were conducted among
      twin pairs discordant for depression. Bivariate genetic modelling was used to
      examine genetic and environmental components of the correlation between smoking
      and depression. RESULTS: Among the men, persistent smoking (OR 1 x 42, 95% CI 1 x
      07-1 x 89) and smoking in 1975 but quitting by 1981 (OR 1 x 68, 95% CI 1 x 17-2 x
      42) was associated with a higher risk of depression, while among the women only
      the quitters had an elevated risk (OR 1 x 38, 96% CI 1 x 01-1 x 87). The gender x
      smoking interaction showed persistent smoking to be a stronger risk for men. When
      family and genetic background were controlled, smoking remained a predictor of
      depression. Genetic modelling among the men suggested a modest correlation (rg=0
      x 25) between genetic components of smoking and depression. CONCLUSIONS: Smoking
      behaviour may be a gender-sensitive predictor of depression, the stronger
      association in men being partly accounted for by having underlying genes in
      common.

PMID- 17181914
TI  - Emerging epidemic diseases of frogs in Britain are dependent on the source of
      ranavirus agent and the route of exposure.
AB  - A series of transmission studies was conducted to investigate the aetiology, or
      aetiologies, of emerging fatal epidemic disease syndromes affecting the common
      frog (Rana temporaria) in Britain. The syndromes, characterized by skin
      ulceration or systemic haemorrhages, were induced upon exposure to lesion
      homogenates or cultured ranavirus. The re-isolation of ranavirus from
      experimentally affected frogs fulfilled Koch's postulates. Aeromonas hydrophila,
      previously associated with similar lesions, was not significant to disease
      development. Unexpectedly, disease outcomes were influenced by both the source of
      agent and the route of exposure, indicating that different ranaviruses with
      different tissue tropisms and pathogeneses (possibly similar to quasi-species in
      RNA virus populations) are circulating in the British common frog population. Our
      findings confirm that ranavirus disease has emerged as an important cause of
      amphibian mortality in Britain.

PMID- 17181915
TI  - Is B-cell the conductor of the lymphocyte orchestra in the salivary glands of
      patients with primary Sjogren's syndrome.

PMID- 17181916
TI  - Ultrasound imaging for the rheumatologist V. Ultrasonography of the ankle and
      foot.
AB  - Ultrasonography (US) is a useful tool for imaging, which can be used for the
      assessment of joints and periarticular structures in all rheumatological
      disorders. In patients with pain and/or swelling of the ankle and foot, US
      provides information about the presence of joint effusion, synovitis,
      tenosynovitis, tendinosis, and tendons tears, helping in the differential
      diagnosis between joint or tendon/enthesis involvement. Moreover, US allows
      clinicians to monitor and guide needle positioning to inject pharmaceutical
      substances more safely and effectively even in hard-to-reach sites. US represents
      an accurate, safe and low-cost technique that can be used for the examination of
      the ankle and foot in rheumatic disorders.

PMID- 17181917
TI  - Epidemiology of rheumatoid arthritis, juvenile idiopathic arthritis and gout in
      two regions of the Czech Republic in a descriptive population-based survey in
      2002-2003.
AB  - OBJECTIVE: To estimate the annual incidence and prevalence of rheumatoid
      arthritis (RA), juvenile arthritis (JIA) and gout in a population based study in
      two regions of the Czech Republic with total population of 186,000 inhabitants.
      METHODS: The study was conducted in the Town of Ceske Budejovice and district of
      Cheb in the Czech Republic (with a total population of 186,000 inhabitants) in
      the years 2002 and 2003. Incident cases were registered on condition that the
      definite diagnosis was confirmed according to existing classification criteria
      during the study period. Prevalence was studied on the basis of identification of
      established diagnosis from registers of patients of participating rheumatologists
      and other specialists. They were asked to report all living patients who had been
      diagnosed before 1st March 2002. Patients were only included in the study if
      their permanent address was in the selected study area. RESULTS: Overall, we
      found 48 incident and 947 prevalent cases of RA among adults (16+ years), 4
      incident and 43 prevalent cases of JIA among children (less than 16 years old),
      and 64 incident and 425 prevalent cases of gout among adults (16+ years). The
      total annual incidence of RA was 31/100,000 in the adult population aged 16 years
      and more (95% CI 20 to 42/100,000). The prevalence of RA was 610/100,000 (95% CI
      561 to 658/100,000) in the adult population. An annual incidence of gout in
      adults was 41/100,000 (95% CI 28 to 53/100,000). The prevalence of gout was
      300/100,000 (95% CI 266 to 334/100,000). The annual incidence of JIA was
      13/100,000 in children less than 16 years old (95%CI 1 to 20/100,000). The
      prevalence of JIA in children was 140/100,000 (95% CI 117 to 280/100,000).
      CONCLUSION: This study estimates the annual incidence and prevalence rates of RA,
      gout and JIA in the first population-based survey in the Czech Republic. The
      rates of RA and JIA compare well with figures reported from other countries;
      figures in gout seem to be lower than reported elsewhere.

PMID- 17181918
TI  - Decreased ratio of circulatory vascular endothelial growth factor to endostatin
      in patients with systemic sclerosis--association with pulmonary involvement.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) and endostatin appear to be
      involved in development of systemic sclerosis (SSc). We undertook this study to
      determine ratios of serum concentrations of VEGF to endostatin in SSc patients,
      healthy controls, assessments between cytokines, and lung-diffusing capacity
      (DLCO) as lung injury measurements related to interstitial lung disease (ILD).
      MATERIALS AND METHODS: Serum VEGF and endostatin levels were measured with ELISA
      in 28 SSc patients (16 with lcSSc) and 20-matched healthy volunteers, evaluating
      correlation and balance. DLCO was corrected for hemoglobin, alveolar volume, and
      determined with a single breath technique. RESULTS: SSc serum concentrations
      (median; range) of endostatin were higher than controls (107.2; 13.6-261.2 vs.
      77.8; 18.0-110.4 ng/ml, p < 0.05); VEGF levels did not differ (151.2; 4.5-836.4
      vs. 286.4; 23.7-708.5 pg/ml, p < 0.05). Ratios of VEGF to endostatin were 2.6 and
      3.6 times lower (p < 0.05) in SSc and dcSSc in comparison to healthy subjects.
      There were significant negative correlations between VEGF, endostatin in SSc (r =
      -0.51), and controls (r = -0.57). SSc with ILD (n = 20) had similar
      concentrations of VEGF, endostatin, and ratios of VEGF to endostatin compared to
      SSc alone. No correlations were seen between DLCO, VEGF, endostatin and their
      ratios in the whole SSc group. Negative correlations were noted between DLCO and
      VEGF (r = -0.82), with DLCO and the ratio of VEGF to endostatin (-0.62) in lcSSc
      with ILD (n = 10). CONCLUSION: Decreased ratios of VEGF to endostatin may reflect
      imbalances between serum angiogenic, and anti-angiogenic activity in SSc,
      explaining impaired neoangiogenesis.

PMID- 17181919
TI  - Polymerized-type I collagen for the treatment of patients with rheumatoid
      arthritis. Effect of intramuscular administration in a double blind placebo
      controlled clinical trial.
AB  - OBJECTIVE: To determine the efficacy, tolerance and safety of intramuscular
      injections of porcine type I collagen-PVP in patients with RA in a long term
      therapy. METHODS: The study was a double blind placebo-controlled and included 30
      patients with active RA (ACR). Patients were treated with intramuscular
      injections of 2 ml of collagen-PVP (3.4 mg of collagen) or 2 ml of placebo during
      6 months. The follow up was done during the next 6 months. The primary endpoints
      included the Ritchie index (RI), swollen joint count, disease activity score
      (DAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The
      secondary endpoints included morning stiffness, pain intensity on a visual
      analogue scale (VAS), and Spanish-health assessment questionnaire (HAQ-DI).
      Improvement was determined using American College of Rheumatology response
      criteria (ACR20, 50 and 70). RESULTS: Collagen-PVP was safe and well tolerated.
      There were no adverse events. Patients had a statistically significant
      improvement (p < 0.05) in collagen-PVP-treated vs. placebo at 6 months of
      treatment in: swollen joint count (7.1 +/- 0.8 vs. 16.0 +/- 1.6), RI (8.1 +/- 0.8
      vs. 15.2 +/- 1.5), morning stiffness (9.2 +/- 3.1 vs. 29.1 +/- 5.9 min), HAQ-DI
      (50.0 +/- 10.8 vs. 22.9 +/- 10.3), DAS (3.0 +/- 0.2 vs. 4.9 +/- 0.3), ACR20 (78.6
      vs. 71.4%), ACR50 (57.1 vs. 0%) and ACR70 (7.1 vs. 0%) and CRP (1.1 +/- 0.4 vs.
      2.5 +/- 0.7). Patients treated with collagen-PVP required lower doses of
      methotrexate vs. placebo (12.6 +/- 0.6 vs. 14.2 +/- 0.7 at 6 months and 12.3 +/-
      0.8 vs. 15.4 +/- 0.6 at 12 months; p < 0.05). Serological or haematological
      parameters remained unchanged. CONCLUSION: Collagen-PVP has been shown to be a
      safe and well-tolerated drug for the long-term treatment of RA. Combination of
      collagen-PVP plus methotrexate was more efficacious than methotrexate alone. This
      biodrug can be useful in the treatment of RA.

PMID- 17181920
TI  - Brazil Patient Knowledge Questionnaire (PKQ) and evaluation of disease-specific
      knowledge in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To create a Brazilian version of the Patient Knowledge Questionnaire-
      PKQ, an instrument for measuring the knowledge of patients with rheumatoid
      arthritis (RA) as regards their disease, and through the use of this instrument,
      also measure the knowledge of RA patients from reference hospitals in the city of
      Sao Paulo. METHODS: Two teachers of English translated the PKQ into Portuguese in
      order to obtain a single version, which was then translated back into English to
      evaluate its equivalence to the original version (back translation). The final
      version in Portuguese was applied to 20 patients with RA for adaptation to
      cultural issues, and questions not understood by 20% or more patients were
      subsequently modified. Inter- and intraobserver reliability and the constructive
      validity of the PKQ were tested. The questionnaire was then applied to 100 RA
      patients, selected in four outpatient clinics at reference hospitals in the city
      of Sao Paulo. RESULTS: Three of the PKQ questions were modified to adapt to
      cultural issues. Intraclass correlation coefficients used for the reliability and
      validity of the PKQ were between were between 0.62 and 0.94, therefore,
      statistically significant (p< 0.05). The mean PKQ score was 12.96 and the mean
      test application time was 10.3 minutes, for the 100 patients assessed. The lowest
      scores were observed in the domains of medications and joint protection/energy
      conservation. PKQ scores showed a positive correlation with the level of
      education (r=0.40) and a negative correlation with the patients' age (r= -0.32)
      and with HAQ (r= -0.28). CONCLUSION: The Brazilian version of the PKQ that was
      created and proved to be a reliable and valid instrument. Patients' knowledge of
      RA is poor, particularly in the domains regarding medications and joint
      protection/energy conservation.

PMID- 17181921
TI  - Regulation of serum chemokines following infliximab therapy in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: We studied the effects of the multiple infusions of infliximab, a
      chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) antibody, on the serum
      chemokines levels in patients with active rheumatoid arthritis (RA). METHODS: RA
      patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0,
      2, 6, and every 8 weeks thereafter with the same dose. All patients continued
      treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of
      interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed
      and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by
      ELISA at weeks 0, 2, 6, 14, 38, prior to infusion, and additionally at week 62.
      RESULTS: Initial infusion of infliximab caused reduction in serum IL-8, RANTES
      and MCP-1 (in all cases p < 0.001) levels. Subsequent infliximab administrations
      also significantly decreased serum chemokines levels, but was less effective.
      Prior to the first infliximab infusion serum concentrations of studied chemokines
      correlated with markers of RA activity such as the erythrocyte sedimentation rate
      (ESR) or CRP levels, number of swollen joints and disease activity score (DAS).
      Following next drug infusions such associations were far less significant.
      Infliximab treatment induced a significant reduction in the number of monocytes
      observed through the whole study (in all cases p < 0.05). CONCLUSION: Anti-TNF
      alpha antibody therapy accompanied by MTX, beside a rapid clinical improvement,
      reduced serum chemokines concentrations in RA patients. Subsequent
      administrations of infliximab sustained chemokines decrease, although to a lesser
      extent than the first two dose of infliximab.

PMID- 17181922
TI  - Interferential and horizontal therapies in chronic low back pain: a randomized,
      double blind, clinical study.
AB  - OBJECTIVE: Chronic Low Back Pain (CLBP) is one of the most frequent medical
      problems. Electrical nerve stimulation is frequently used but its efficacy
      remains controversial. METHODS: Twenty-six men and 94 women with CLBP associated
      with either degenerative disk disease or previous multiple vertebral osteoporotic
      fractures were randomly assigned to either interferential currents (IFT),
      horizontal therapy (HT) or sham HT administered for 10, 40 and 40 minutes,
      respectively, daily for 5 days per week for two weeks together with a standard
      flexion-extension stretching exercise program, Blind efficacy assessment were
      obtained at baseline and at week 2, 6 and 14 and included a functional
      questionnaire (Backill), the standard visual analog scale (VAS) and the mean
      analgesic consumption. RESULTS: At week 2 a significant and similar improvement
      in both the VAS and Backill score was observed in all three groups. The Backill
      score continued to improve only in the two active groups with changes
      significantly greater than those observed in control patients at week 14. The
      pain VAS score returned to baseline values at week 6 and 14 in the control group
      while in the IFT and HT groups it continued to improve (p< 0.01 vs controls). The
      use of analgesic medications significantly improved at week 14 versus
      pretreatment assessment and over control patients only in the HT group.
      CONCLUSION: This randomized double-blind controlled study provides the first
      evidence that IFT and HT therapy are significantly effective in alleviating both
      pain and disability in patients with CLBP. The placebo effect is remarkable at
      the beginning of the treatment but it tends to vanish within a couple of weeks.

PMID- 17181923
TI  - Comparison of functional disability scales and their relevance to radiological
      progression in patients with rheumatoid arthritis in remission.
AB  - OBJECTIVE: To look for any correlations between radiological scores and hand
      functions evaluated with two different methods in patients with rheumatoid
      arthritis in remission. METHODS: Forty-two patients diagnosed with rheumatoid
      arthritis (RA) in remission according to ACR criteria were assessed for their
      hand functions with Duruoz's Hand Index (DHI), and with Sollerman Function Test
      (SHFT) as well as with Health Assessment Questionnaire (HAQ). Hand X-rays were
      evaluated according to Modified Sharp Index; joint space narrowing score (JSNS),
      erosion score (ES), and total score (TS) were calculated. The X-rays were
      assessed by the same rheumatologist three times. RESULTS: Mean HAQ score, mean
      DHI score and mean SHFT scores were 0.88+/-0.68, 17.74+/-17.81, 72.24+/-9.23
      respectively. Radiologic scores were as follows: JSN 35.04+/-28.14, ES 25.19+/
      36.23, TS 60.26+/-66.21. Intraobserver reliability was high (r=0,98). There was a
      positive correlation between HAQ and DHI (p<0.001), a negative correlation
      between SHFT. There was also a negative correlation between DHI and SHFT. The
      correlations between JSNS, ES and TS with respect to HAQ and SHFT were strong
      (p<0.0001) along with DHI (p<0.05). CONCLUSION: HAQ was found correlated with DHI
      and SHFT. Modified Sharp scores were found correlated with the general disability
      and hand functions. SHFT, with respect to DHI, takes a longer period of time,
      depends on equipment and needs an observer. On the contrary, DHI offers a more
      practical and economical way of assessment.

PMID- 17181925
TI  - Sexual functioning of women with fibromyalgia.
AB  - OBJECTIVE: To examine sexual functioning at the specific phases of the sexual
      response cycle among women with fibromyalgia. METHODS: The Questionnaire for
      screening Sexual Dysfunctions - Short Form (QSD-SF) was filled out by 63
      premenopausal, heterosexual women with fibromyalgia (age: 21-54 years) who were
      recruited at meetings of regional patient associations. RESULTS: The women with
      fibromyalgia did not differ from healthy women of an age reference group with
      respect to functioning in the excitement and the orgasm phases, but reported more
      problems with sexual desire and satisfaction, more pain in their body, and
      insensitivity (but not pain) in their genitals before, during or after having
      sex. Mental distress, but not pain, was a significant predictor of virtually all
      aspects of sexual dysfunction. CONCLUSION: Our study generates the hypothesis
      that the psychological but not the physiological aspect of the sexual response
      cycle is more disturbed than normal in fibromyalgia. This finding needs
      confirmation in a more representative population.

PMID- 17181924
TI  - ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid
      arthritis patients.
AB  - OBJECTIVE: Methotrexate (MTX) is most widely used for the treatment of rheumatoid
      arthritis (RA). However, it has certain drawbacks with regard to individual
      differences in its therapeutic effects as well as the differences in the
      patients' response to MTX therapy. We investigated whether multi-drug resistance
      1 (ABCB1) C3435T, reduced folate carrier-1 (RFC1) G80A, 5-aminoimidazole-4
      carboxamide ribonucleotide transformylase (ATIC) C347G and a 6bp-deletion
      polymorphism in the 3'-untranslated region of the thymidylase synthase (TYMS)
      gene are predictive of MTX sensitivity and its adverse effects. METHODS: Patients
      whose last maintenance dosage of MTX was <or= 6 mg/week were regarded as
      responders, while patients whose last maintenance dosage of MTX was > 6 mg/week
      or those in whom MTX therapy was changed due to poor response to MTX were
      regarded as non-responders. The data of 124 RA patients who had received MTX
      treatment were retrospectively analyzed for polymorphisms in the ABCB1, RFC1,
      ATIC and TYMS genes, MTX sensitivity and MTX toxicity. RESULTS: There were no
      significant differences in MTX sensitivity among the genotypes of RFC1, ATIC and
      TYMS genes. ABCB1 3435TT cases included statistically significantly more non
      responders than 3435CC cases according to univariate analysis (crude odds ratio
      (OR) = 8.91, p = 0.001) and multivariate analysis (adjusted OR = 8.78, p =
      0.038). There were no significant differences in MTX toxicity among the genotypes
      of all the genes. CONCLUSION: These results suggested that the genetic diagnosis
      of ABCB1 C3435T can be applied to determine MTX sensitivity for the treatment of
      RA patients. However, further pharmacokinetics studies are required in this
      regard.

PMID- 17181926
TI  - Synovial expression of vasoactive intestinal peptide in polymyalgia rheumatica.
AB  - OBJECTIVE: Polymyalgia rheumatica (PMR) is an inflammatory disease that typically
      affects elderly people. Its clinical hallmark is the severity of pain in the
      shoulder and pelvic girdle. Mild to moderate synovitis and/or bursitis of the
      joints involved has been described. Neuropeptides are involved in nociception and
      modulation of inflammatory reaction. To evaluate whether neuropeptides have a
      role in PMR pathophysiology, we studied the expression of substance P (SP),
      calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and
      somatostatin (SOM) in shoulder synovial tissues of PMR patients. METHODS:
      Synovial expression of neuropeptides was investigated by immunohistochemical
      analysis, in two groups of PMR patients: the first one at the onset of disease
      and the second one after corticosteroid treatment, and in other joint diseases,
      rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: The only significant
      expression of VIP was found in PMR and, to a lesser extent, in RA synovial
      tissue. In PMR, we observed VIP immunostaining both in the lining layer and in
      the sublining area. In patients on corticosteroid treatment VIP lining layer
      expression was not significantly different while VIP positive cells in the
      sublining area were almost absent. CONCLUSION: Local VIP production in PMR
      synovial tissue might contribute to the typical musculoskeletal discomfort and it
      may have a role in the immunomodulation of synovial inflammation.

PMID- 17181927
TI  - A proposal of new ocular items in Sjogren's syndrome classification criteria.
AB  - OBJECTIVE: To verify whether ocular surface tests other than those included in
      primary Sjogren's syndrome (SS-I) classification criteria (Schirmer I, Break up
      Time, vital dye staining) may contribute to SS I diagnosis. METHODS: Two hundred
      and sixty-two patients (78 SS-1, 91 non-SS autoimmune diseases, 93 Sicca
      syndrome) filled a validated questionnaire on symptoms and were evaluated by
      Schirmer test without (Schirmer I) and with (Jones test) topical anaesthesia,
      Break Up Time (BUT), corneal aesthesiometry, tear clearance rate, vital dye
      (lissamine green) staining, impression conjunctival cytology, concentration of
      tear lysozyme and lactoferrin. Thresholds were selected from Receiver Operating
      Curves; sensitivity, specificity, likelihood ratio (LR+), predictive values were
      calculated for each test. A logistic regression model was constructed
      representing the best diagnostic index for SS. RESULTS: Data showed a poor
      diagnostic performance of Schirmer test I (LR+ 1.38) and BUT (LR+ 1.05); results
      from lissamine green staining may be unreliable due to incorporation bias. Tear
      lactoferrin (LR+ 4.52), Jones test (LR+ 6.24), tear lysozyme (LR+ 8.0), symptom
      questionnaire (LR+ 8.62), tear clearance rate (LR+ 18.73) and corneal
      aesthesiometry (LR+ 20.96) exhibited high diagnostic performance also taken
      together in the regression model. CONCLUSION: Because many of the tests we have
      screened in this study can be carried out by a trained ophthalmologist in any
      clinical setting, we recommend that ocular surface impairment is studied with the
      combination of tests proved to be helpful for the SS I diagnosis.

PMID- 17181929
TI  - Lack of association between macrophage migration inhibitory factor gene (-173
      G/C) polymorphism and cutaneous vasculitis.
AB  - OBJECTIVE: To assess whether polymorphism of the macrophage migration inhibitory
      factor (MIF) gene at position -173 was implicated in the incidence of Henoch
      Schonlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA). A further
      objective was to determine if any relationship existed with severe systemic
      complications of HSP, in particular with severe renal involvement and permanent
      renal dysfunction. METHODS: Unselected patients from Northwest Spain with primary
      cutaneous vasculitis classified as HSP or hypersensitivity vasculitis (HV)
      according to proposed criteria were studied. Patients with HV were included in
      this study if they fulfilled the Chapel Hill Consensus Conference on the
      Nomenclature of Systemic Vasculitis definitions for CLA. Patients and controls
      were genotyped for a single nucleotide polymorphism (SNP) in the 5'-flanking
      region at position -173 of the MIF gene, using SNapshot ddNTP primer extension,
      followed by capillary electrophoresis (ABI 3100). RESULTS: Ninety-five Caucasian
      patients (57 classified as having HSP and 38 who fulfilled definitions for CLA)
      and 122 healthy controls were studied. No allele or genotype differences between
      the whole group of HSP or CLA patients and controls were observed. This was also
      the case when HSP patients were stratified by the presence of gastrointestinal
      complications, nephritis, and permanent renal involvement (renal sequelae).
      CONCLUSION: The polymorphism in MIF gene promoter (-173 G/C) does not appear to
      be genetic risk factors for cutaneous vasculitis in Northwest Spain.

PMID- 17181928
TI  - CDRAP is expressed in adult articular cartilage, but its expression is not
      significantly regulated in osteoarthritic chondrocytes.
AB  - OBJECTIVE: In this study we assessed the differential in vivo mRNA expression
      levels of CDRAP, a potential marker of cartilage degeneration. METHODS:
      Conventional and real time PCR in a large series of normal (n = 18) and late
      stage osteoarthritic (n = 24) cartilage specimens were performed. RESULTS:
      Conventional PCR analysis could demonstrate the presence of CDRAP mRNA in normal
      and osteoarthritic chondrocytes. Real time quantitative PCR confirmed the
      presence of CDRAP mRNA expression in normal articular chondrocytes in vivo (and
      in vitro). No significant up-regulation of CDRAP was observed in osteoarthritic
      chondrocytes in vivo. CONCLUSION: The presented results confirm expression of
      CDRAP by normal and osteoarthritic articular chondrocytes, but indicate that
      increased expression levels by chondrocytes are not the cause of the increased
      levels of CDRAP in the synovial fluid of patients with osteoarthritis.

PMID- 17181930
TI  - The effects of TNF alpha inhibition on plasma fibrinolytic balance in patients
      with chronic inflammatory rheumatical disorders.
AB  - OBJECTIVE: Recent studies support an inflammatory basis for atherosclerosis.
      Patients with chronic inflammatory rheumatical disorders are at increased risk
      for cardiovascular events, and this can be partially attributed to the inhibition
      of fibrinolytic system. TNF a inhibitors such as infliximab are shown to retard
      the progression of inflammatory arthritides. In this study, we investigated the
      effects of infliximab on plasma fibrinolytic parameters. METHODS: Thirteen
      patients (7 female, 6 male; mean age: 44 +/- 11 years) with a clinical indication
      for infliximab (rheumatoid arthritis (RA) (n = 8), ankylosing spondylitis (AS) (n
      = 5)) were selected. Plasma plasminogen activator inhibitor (PAI-1), tissue
      plasminogen activator (t-PA) antigens (Ag) and high sensitive C-reactive protein
      (hs-CRP) levels were measured during low salt intake at baseline. All patients
      received infliximab (Remicaide, i.v. infusion, 3 mg/kg). Plasma PAI-1 Ag, t-PA Ag
      and hs-CRP were measured during low salt intake at the end of 2 weeks. All
      samples were collected at 9 AM. Antigen levels were determined using a 2-site
      enzyme-linked immunosorbent assay. RESULTS: Patients experienced significant
      improvement in disease related activity scores after infliximab treatment. DAS
      score (for rheumatoid arthritis) and BASDAI index (for ankylosing spondylitis)
      decreased significantly after treatment (p = 0.01 and p = 0.04 respectively).
      Infliximab significantly reduced the marker of inflammation (hs-CRP) (8.3 +/- 3.9
      vs. 4 +/- 4.1 mg/L, p < 0.01). Plasma PAI-1 antigen (64.7 +/- 26.9 vs. 40 +/-
      31.1 ng/ml, p = 0.03) and PAI-1/t-PA ratio (10.8 +/- 5.9 vs. 6.6 +/- 3.8, p =
      0.02) were significantly lower after the treatment. In contrast, plasma t-PA
      levels were unchanged (9.4 +/- 4.4 vs. 9.0 +/- 4.3 ng/ml, p = 0.73). CONCLUSION:
      This study provides evidence that TNF alpha inhibition with infliximab decreases
      PAI-1 Ag level and PAI-1/t-PA ratio, and hence activates fibrinolytic system in
      patients with chronic inflammatory disorders.

PMID- 17181931
TI  - Wegener's granulomatosis masquerading as a renal cancer: a case report and review
      of the literature.
AB  - A 32 year-old man presented with sinusitis, proteinuria, mononeuritis multiplex,
      very increased acute phase proteins. Anti-PR3 ANCA were detected and Wegener's
      granulomatosis (WG) was diagnosed. As abdominal tomodensitometry detected a
      tumoral process of the left kidney, a paraneoplastic vasculitis associated with a
      renal cancer was suspected. Biopsy of the mass showed fibrosis, inflammatory
      infiltrates and necrotizing granulomas. No malignant cells were detected. The
      outcome was favourable after administration of methylprednisolone and
      cyclophosphamide. Characteristics of the nine previously reported renal
      inflammatory pseudotumors associated with WG are discussed.

PMID- 17181932
TI  - Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic
      review.
AB  - OBJECTIVE: To review the evidence on the clinical effectiveness of etanercept and
      infliximab for the treatment of active and progressive psoriatic arthritis (PsA)
      in patients with an inadequate response to standard treatment (including DMARD
      therapy). METHODS: A systematic review was conducted. The literature search
      covered a range of 13 medical databases and submissions were provided by the
      manufacturers of etanercept and infliximab. Randomised controlled trials (RCTs)
      of etanercept or infliximab that reported outcomes of disease activity in PsA
      were reviewed. RESULTS: There were two good quality double-blind, placebo
      controlled RCTs each for etanercept and infliximab. The results demonstrated that
      after initial treatment (12 weeks for etanercept and 14 or 16 weeks for
      infliximab) both drugs had statistically significant beneficial effects compared
      with placebo on ACR 20, 50 and 70, PsARC and HAQ scores. Efficacy was not
      dependent upon concomitant methotrexate. Results at 24 weeks indicated that the
      response to treatment is maintained. Effects on psoriasis were beneficial,
      particularly with infliximab. Uncontrolled radiographic assessment data at one
      year indicated a beneficial effect of both etanercept and infliximab on the
      progression of joint disease. CONCLUSION: Our review indicates that both
      etanercept and infliximab are efficacious in the treatment of PsA with beneficial
      effects on both joint and psoriasis symptoms and on functional status. There are
      limited data indicating that etanercept and infliximab can delay joint disease
      progression. Further long-term data are required to confirm and consolidate the
      evidence base for both drugs.

PMID- 17181933
TI  - Increased concentration of plasma homocysteine in children with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Studies in adults with SLE have evidenced increase of homocysteine
      related, mainly, to thromboembolic events. The aim of our study was to evaluate
      plasma homocysteine concentration in children with systemic lupus erythematosus
      (SLE) and its correlation with renal involvement, serum and erythrocyte folate,
      vitamin B12, antiphospholipid antibodies, estimated creatinine clearance and
      dyslipidemia. METHODS: Thirty-two children (29 females) with SLE and 32 healthy
      controls (29 females) matched for age and sex were included in the study. The
      mean age of patients and controls was 14.2 years (range from 10 to 18 years).
      Only one patient presented one thrombotic event. Plasma homocysteine, erythrocyte
      and serum folate, vitamin B12, lipid profile, antiphospholipid antibodies and
      estimated creatinine clearance were evaluated. Raised homocysteine concentration
      was defined as equal or more than 12.9 mol/L. RESULTS: Raised homocysteine
      concentration was detected in 15 (46.9%) children with SLE with an important
      statistical difference in relation to control group (p < 0.001). A positive
      correlation was found between plasma homocysteine concentration and renal
      involvement (odds ratio 11.1 [95% CI 1.50-82.24], p = 0.01) based on the presence
      of renal biopsy, abnormalities of urine sediment and/or serum creatinine.
      However, when we performed the estimated creatinine clearance the correlation
      with homocysteine concentration was not positive. We did not observe
      abnormalities in serum and erythrocyte folate and vitamin B12 in our patients.
      However, they presented significant higher concentrations of TC total cholesterol
      (p = 0.005) and of LDL low-density lipoprotein (p = 0.02) than controls.
      CONCLUSION: Elevated plasma homocysteine concentration is frequent in children
      with SLE. We believe that these results may signalize to the possibility of
      complications in our patients later in life. Further long-term and prospective
      studies are needed in order to determine the real role of the homocysteine
      concentration as a risk factor in children.

PMID- 17181934
TI  - Cyclosporine A in juvenile idiopathic arthritis. Results of the PRCSG/PRINTO
      phase IV post marketing surveillance study.
AB  - OBJECTIVE: To investigate the clinical use patterns, clinical effect and safety
      of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of
      routine clinical care. METHODS: An open-ended, phase IV post marketing
      surveillance study was conducted among members of the Pediatric Rheumatology
      Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology
      International Trials Organisation (PRINTO) to identify patients with
      polyarticular course JIA who had received CSA during the course of their disease.
      RESULTS: A total of 329 patients, half of whom had systemic JIA, were collected
      in 21 countries. Data were collected during 1240 routine clinic visits. CSA was
      started at a mean of 5.8 years after disease onset and was given at a mean dose
      of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and
      along with prednisone in 65% of the patients who were still receiving CSA. Among
      patients who were still receiving CSA therapy at the last reported visit,
      remission was documented in 9% of the patients, whereas in 61% of the patients
      the disease activity was rated as moderate or severe. The most frequent reason
      for discontinuation of CSA was insufficient therapeutic effect (61% of the
      patients); only 10% of the patients stopped CSA because of remission. In 17% of
      the patients, side effects of therapy was given as the primary reason for
      discontinuation. CONCLUSION: This survey suggests that CSA may have a less
      favourable efficacy profile than MTX and etanercept, whereas the frequency of
      side effects may be similar. The exact place of CSA in the treatment of JIA can
      only be established via controlled clinical trial.

PMID- 17181935
TI  - A case of Whipple disease with pleural effusion diagnosed by means of PCR.

PMID- 17181936
TI  - Development of type 1 diabetes mellitus in a patient with rheumatoid arthritis
      receiving anti-tumor necrosis factor alpha.

PMID- 17181937
TI  - Eosinophilic fasciitis in a patient with psoriasis: an unusual association.

PMID- 17181938
TI  - [Expression of FasL and apoptosis in pulmonary tissue of rats exposed to silica
      at different time].
AB  - OBJECTIVE: To investigate the change of the expression of the FasL receptor and
      apoptosis in the pathology of silicosis of the rats exposed to silica and their
      roles. METHODS: Ninety-six wistar rats were randomizedly divided into the control
      group and the experimental group. The silicotic animal model was established by
      the direct tracheal instillation of silica into rat lungs surgically. The control
      rats underwent directly tracheal instillation of saline into lungs surgically.
      Eight rats from each group were sacrificed at different days. The expression of
      FasL receptor in the tissue of the model rats was detected by tissuechip
      microarray and immunohistochemistry and the cell apoptosis induced by silica was
      determined by TdT-mediated dUTP nick end-labeling method. The integral optical
      density of positive cells were quantitatively analyzed using Image-Pro Plus
      Version 4.5 for windows. RESULTS: The expression of FasL in the lung tissue of
      the model rats on the 7th, the 14th, the 21st, and the 28th day was significantly
      higher than that in the control group (P < 0.05), and peaked at the 14th day
      after exposure to silica. Apoptotic cells in the lung tissue of the model rats on
      the 1st, the 3rd, the 7th, the 14th, the 21st, and the 28th day were
      significantly more than those in the control group, and peaked at the 7th and the
      14th day after exposure to silica. CONCLUSION: Silica can lead to apoptosis in
      lung tissues. FasL is expressed in all kinds of cells in the pulmonary tissues of
      the rats exposed to silica and leads to apoptosis. From the 7th day to 14th day,
      inflammatory cells dominate in apoptotic cells.

PMID- 17181939
TI  - [Effect of dimethoate on serum monoamines neurotransmitters in rats].
AB  - OBJECTIVE: To study the effect of dimethoate on the monoamine Neurotransmitters,
      including norepinephrine (NE), epinephrine (E), serotonin (5-HT), dopamine (DA)
      and its metabolite (3, 4-hydroxyphenylacetic acid, DOPAC) in the serum of rats
      and furthermore to explore the non-cholinergic mechanism of organophosphate
      induced toxicity. METHODS: Groups of rats were treated with saline and 38.9, 83.7
      and 180 mg/kg dimethoate respectively and were decapitated at the different time
      course from 0.5 to 24 hours after the administration. The monoamines
      neurotransmitters were determined by the reverse-phase high-performance liquid
      chromatography with the electrochemical detection. RESULTS: The serum
      concentrations of DA (8.42% - 248.42% of the control), DOPAC (17.22% - 68.21% of
      the control) increased, according with the DM dosage and the exposure time, while
      the levels of NE (9.65% - 38.26% of the control) and E (11.00% - 32.62% of the
      control) contents decreased at the same time. CONCLUSION: These findings indicate
      that dimethoate induced toxic effects can alter the monoamine levels at the
      different dosage and the time exposure in the serum of rats. It suggests that
      some non-cholinergic mechanisms may be involved in the dimethoate intoxication.

PMID- 17181940
TI  - [Scanning aneugen and clastogen by micronuclei analysis using flow cytometry].
AB  - OBJECTIVE: To explore a flow cytometry (FCM)-based method for discriminating
      aneugen- or clastogen-induced micronuclei. METHODS: Cells were stained with anti
      CD71-FITC and PI, and the PI fluorescent signal intensity of micronucleated
      reticulocyte (MN-RET) in the peripheral blood of NIH mouse treated with COL or CP
      was detected by flow cytometry. RESULTS: The ratio of the median of the intensity
      of MN-RET fluorescent signals to that of nucleated cell was low in the
      cyclophosphamide treated mouse, while the median was high in the colchicine
      treated mouse. CONCLUSION: The flow cytometry-based micronucleus assay can be
      used to discriminate primarily smaller MN induced by the clastogen exposure from
      the larger MN induced by an aneugen.

PMID- 17181941
TI  - [Effects of lead acetate on expression of brain-derived neurotropic factor and
      P75NTR in rat brain].
AB  - OBJECTIVE: To study the effects of lead acetate on the expression of brain
      derived neurotropic factor (BDNF) and its receptor P75NTR in rat brain. METHODS:
      Lead acetate was given to SD rats by intraperitoneal injection (ip) for 5 days at
      the dosage of 25, 50 and 100mg/kg body weight respectively. The contents of lead
      in serum, cerebral cortex and hippocampus were measured by atomic absorption
      spectrophotochemistry. The levels of BDNF mRNA and protein expression in cerebral
      cortex and hippocampus were observed by RT-PCR and immunohistochemistry,
      respectively. The levels of P75NTR protein expression in rat brain were measured
      by immunohistochemistry. RESULTS: Compared with the control, the contents of lead
      were significantly increased in serum, cerebral cortex and hippocampus in the
      treatment groups respectively (P < 0.01, P < 0.05). The BDNF mRNA expression in
      the cerebral cortex (0.52 +/- 0.05, 0.33 +/- 0.03) and hippocampus (0.77 +/-
      0.10, 0.92 +/- 0.08) of 50, 100 mg/kg treated groups was significantly higher
      than that of the control group (0.52 +/- 0.05, 0.33 +/- 0.03), respectively (P <
      0.05). The results of immunohistochemistry showed that the area density of BDNF
      protein in cerebral cortex of every treatment group (0.040 +/- 0.027, 0.048 +/-
      0.027, 0.086 +/- 0.040) was significantly increased whereas the average gray
      value (187.11 +/- 11.15, 180.53 +/- 5.82, 180.15 +/- 8.01) was significantly
      lower than that of the control (0.026 +/- 0.005, 204.98 +/- 3.45) (P < 0.05, P <
      0.01). The area density of BDNF protein in hippocampus of every treatment group
      was 0.040 +/- 0.027, 0.048 +/- 0.027, 0.086 +/- 0.040, respectively, which was
      significantly increased compared with the control (0.045 +/- 0.019, P < 0.05).
      The average gray value of BDNF protein in hippocampus (181.03 +/- 5.16, 171.25 +/
      12.65) of 50, 100 mg/kg were significantly lower than that of the control
      (198.98 +/- 6.40, P < 0.01). There was no positive expression of P75NTR protein
      in the control and 25 mg/kg body weight groups. The positive expression of P75NTR
      protein was detected in 50 and 100 mg/kg body weight groups. CONCLUSION: Lead can
      increase the BDNF and P75NTR expression in rat brain which might play an
      important role in the neural damage and repair.

PMID- 17181942
TI  - [Differential proteomic expression in human liver cells stimulated by
      hydroquinone].
AB  - OBJECTIVE: To explore the differential proteomic expression in human liver cells
      L-02 after exposure to HQ. METHODS: Subcultured L-02 cells were treated by HQ for
      24 h at a 1 x 10(-4) mol/L concentration and a blank group was set as the
      control. Immediately after the treatment, total cellular proteins were extracted
      and separated by 2-DE, and the images were analyzed by PDQuest software. The
      experiment was totally repeated 3 times with 3 repetitions for each group every
      time. The well repeated spots were identified by MALDI-TOF MS and then searched
      in NCBI human protein database with Mascot. RESULTS: About 1,000 spots per gel
      were found. Compared with the control group, 17, 18 and 24 spots were
      significantly altered in 3 separate experiments. The 4 well repeated spots were
      identified by MALDI-TOF MS as Rho GDP dissociation inhibitor GDI alpha, 6
      phosphogluconolactonase, erbB3 binding protein EBP1 and lamin A/C, isoform 1
      precursor. They were involved in cell skeleton, signal transduction and energy
      metabolization in functional classification. CONCLUSION: Hydroquinone can change
      the protein expression in liver cells, which provides clues for exploring the
      toxic mechanism.

PMID- 17181944
TI  - [Effect of cadmium on blood pressure and contractile activity of isolated aortic
      muscle in rabbits].

PMID- 17181943
TI  - [Effects of TCE and PCE on cultured human keratinocyte lipid peroxidation and
      protective effect of vitamin E on it].
AB  - OBJECTIVE: To explore the different concentrations of trichloroethylene (TCE) or
      perchloroethylene (PCE) induced cultured normal human epidermal keratinocyte (KC)
      lipid peroxidation and protective effect of Vitamin E on it. METHODS: KC derived
      from 3 or more donors were pooled together and cultured with K-SFM. Neutral Red
      Uptake Assay was used to determine the IC50 of TCE or PCE, and then different
      concentrations of TCE or PCE were administered for culturing KC; 0.5 mmol/L TCE
      or 0.2 mmol/L PCE and different concentrations of Vitamin E were used to
      determine the protective effect of Vitamin E. After 4 hours' culture, kits were
      used to determine cellular MDA, SOD and ROS level. RESULTS: Treatment of KC with
      different concentrations of TCE or PCE showed significant dose-related variations
      in lipid peroxidation, with the higher concentration, higher level of MDA, ROS
      and lower activity of SOD displayed in this study. Vitamin E 10 - 200 mmol/L dose
      dependently attenuated MDA and ROS level, and increased SOD activities.
      CONCLUSION: TCE or PCE can induce the lipid peroxidation in cultured KC and
      Vitamin E protects it from TCE- or PCE-induced peroxidation.

PMID- 17181945
TI  - [Effect of amine perchlorate on mRNA expression of TGF beta1 and TNFalpha in lung
      tissues of rats].

PMID- 17181946
TI  - [Sensibility of several mouse strains to urethane induced lung tumors].

PMID- 17181947
TI  - [Pathological observation on pulmonary arterioles in coal workers with
      pneumoconiosis and pulmonary heart disease].

PMID- 17181948
TI  - [Detection and evaluation of hazardous risks in various road maintaining working
      environment].

PMID- 17181949
TI  - [Determination of urine muconic acid and biological limit in workers
      occupationally exposed to benzene].

PMID- 17181950
TI  - [HPLC with electrochemiluminescence in determination of ethidium bromide
      remnants].

PMID- 17181951
TI  - [Solid phase extraction--HPLC in determination of coumatetralyl in urine].

PMID- 17181952
TI  - [Determination of hexaazaisowurtzitane with ultraviolet spectrophotometry].

PMID- 17181953
TI  - [Titanium sulphate spectrophotometry in determination of hydrogen peroxide in
      working places].

PMID- 17181954
TI  - [Evaluation of staging indice and complications of pneumoconiosis pathological
      diagnosis criteria].

PMID- 17181955
TI  - [Clinical analysis for thrombocytopenia in 17 workers exposed to high
      concentration benzene].

PMID- 17181956
TI  - [Follow-up study on imaging of inhalation injury induced by gas explosion].

PMID- 17181958
TI  - [Suggestions on amendments of appendix of "Occupational Health Monitoring Control
      Measures"].

PMID- 17181957
TI  - [A three-year follow-up for treatment of coal workers with pneumoconiosis
      complicated with tuberculosis using of loxacin combined with anti-TB drugs].

PMID- 17181959
TI  - [Success in treatment of one patient with multiple organ function injuries
      induced by gas explosion].

PMID- 17181960
TI  - [Review of 2005 year-end final reports of preventive medicine research funded by
      Natural Science Foundation of China].

PMID- 17181961
TI  - [Projects of preventive medicine accepted and supported by Natural Science
      Foundation of China in 2006].

PMID- 17181962
TI  - [Several housekeeping gene mutation experiments and research advances].

PMID- 17181963
TI  - [Current situation and prospect of proteomics research in ovarian malignancies].

PMID- 17181965
TI  - [Proteomic analysis of human ovarian cancer cell lines and their platinum
      resistant clones].
AB  - OBJECTIVE: To perform comparative proteomic analysis of human ovarian cancer cell
      lines for detecting platinum-resistance associated proteins. METHODS: The total
      proteins of two sensitive (SKOV3 and A2780) and four resistant (SKOV3/CDDP,
      SKOV3/CBP, A2780/CDDP and A2780/CBP) human ovarian cancer cell lines were
      separated by two-dimensional gel electrophoresis (2-DE). The differentially
      expressed proteins were analyzed using image analysis software, stained with
      Coomassie Brilliant Blue, then identified using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and
      database searching. The mRNA and protein levels of the differentially expressed
      protein which was most significant in all of the four resistant cell lines were
      validated by RT-PCR and western blotting, respectively. RESULTS: Five proteins
      were found to be significant in four cell lines. Annexin A3 and destrin were up
      regulated and nicotinamide-adenine dinucleotide phosphate (NADP)-dependent
      isocitrate dehydrogenase 1 was down-regulated in all the four resistant samples.
      Glutathione transferase omega 1 had an increased expression in the other three
      resistant cell lines except for SKOV3/CBP in which its expression was not
      changed. However, cofilin 1 represented a different trend. In the two resistant
      sublines of SKOV3, cofilin 1 had a down-regulation, but it had an up-regulation
      in the cell lines induced from SKOV3. The expression of annexin A3 was up
      regulated by 3 - 20 fold and the results of RT-PCR and western blotting showed
      complete consistency with that by 2-DE. CONCLUSIONS: Proteomic techniques are
      useful to the identification of the resistance-associated proteins in ovarian
      cancer platinum-resistant cell lines and five candidates have been found. The
      five differential proteins might become hopeful candidate biomarkers for
      resistance.

PMID- 17181964
TI  - [Inhibitory effects of RNA interference on expression of matrix metalloproteinase
      9 gene and invasiveness and adhesion in ovarian cancer cells].
AB  - OBJECTIVE: To investigate the inhibitory effects of RNA interference (RNAi) on
      the expression of matrix metalloproteinase-9 (MMP-9) gene and invasiveness and
      adhesion of ovarian cancer cells. METHODS: Four groups of different specific
      target sequence in coding region of MMP-9 and one non-specific sequence were
      chosen, which were Site1, Site2, Site3, Site4 and Site5. Small interference RNA
      (siRNA) expression cassettes (SEC) were constructed by PCR and transfected into
      ovarian cancer HO-8910PM cells. RT-PCR and western blot were used to detect mRNA
      and protein expression of MMP-9 gene; the abilities of invasion and adhesion were
      detected by Matrigel invasion assay and cell adhesion assay. RESULTS: The
      expression of MMP-9 was inhibited and the inhibitory effects of different
      sequence were varied. The mRNA expression was 0.64 +/- 0.06, 0.47 +/- 0.07, 0.55
      +/- 0.10 in Site1, Site2, Site3 group, and protein expression was 0.30 +/- 0.09,
      0.27 +/- 0.08, 0.37 +/- 0.12, respectively. Site2 group had the most efficient
      inhibitory effect, followed by Site1 and Site3 groups. Cell growth curve revealed
      that cell growth was significantly inhibited in Site2 group. Invasiveness and
      adhesion were significantly reduced, the inhibitory rate on invasion in Site1,
      Site2, Site3 groups were 50.0%, 50.0% and 37.5%, respectively; the inhibitory
      rate on adhesion in Site1, Site2, Site3, Site4 groups were 43.8%, 48.8%, 33.9%,
      24.2% at 60 min and 41.6%, 40.2%, 35.1%, 16.0% at 90 min, respectively.
      CONCLUSIONS: RNAi exists in ovarian HO-8910PM cells. MMP-9 siRNA can specifically
      down-regulate MMP-9 expression and lead to the inhibition of invasiveness and
      adhesion in ovarian cancer cells.

PMID- 17181966
TI  - [Effects of estrogen receptor beta on proliferation of ovarian clear cell
      adenocarcinoma ES-2 in vitro and in vivo].
AB  - OBJECTIVE: To investigate the involvement of estrogen receptor (ER) beta in the
      proliferation of ovarian clear cell adenocarcinoma by restoring ERbeta expression
      in a cell line ES-2. METHODS: A plasmid with full length ERbeta cDNA, pRSV-ERbeta
      and its negative vector control pRSV were introduced into ES-2. The cells
      transfected were named according to the plasmids: ES-pRSV, ES-pRSV-ERbeta. RT-PCR
      and western blot were used to detect the expression of ERbeta in ES-2, ES-pRSV
      and ES-pRSV-ERbeta cells. The growth activities of cells in vitro were detected
      by methyl thiazolyl tetrazolium (MTT) assay, and in vivo growth in nude mice was
      also observed. Flow cytometry was performed to show the change of cell cycles.
      RESULTS: The ES-pRSV-ERbeta cells were identified with ERbeta mRNA and protein
      expression. The growth activities of ES-pRSV-ERbeta were inhibited in vitro. In
      MTT analysis, the values of ES-2, ES-pRSV, and ES-pRSV-ERbeta cells were 0.78 +/-
      0.05, 0.81 +/- 0.06, and 0.53 +/- 0.07 (the third was lower compared with the
      former two, P < 0.01). In vivo, the volume of transplants of ES-pRSV-ERbeta cells
      in mice, (2868 +/- 879) mm(3) was smaller than that in ES-2, (3603 +/- 724)
      mm(3), and in ES-pRSV, (3913 +/- 624) mm(3) (P < 0.05). The S phase ratios of the
      cell cycle of ES-2, ES-pRSV, and ES-pRSV-ERbeta were (37 +/- 9)%, (39 +/- 10)%,
      and (20 +/- 5)% (P < 0.05). CONCLUSIONS: ERbeta may play an important role in the
      proliferation, and DNA synthesis of ES-2. The evidence indicates ERbeta may be an
      inhibitor in the initiation and development of ovarian clear cell adenocarcinoma.

PMID- 17181967
TI  - [Pregnancy outcomes of 194 couples with balanced translocations].
AB  - OBJECTIVE: To investigate the pregnancy outcomes of couples with either maternal
      or paternal balanced translocations. METHODS: One hundred and ninety-four couples
      were divided into three groups based on the kind of translocations: 135 with
      reciprocal translocation, 52 with nonhomologous Robertsonian translocations, and
      7 with homologous Robertsonian translocations. Past reproductive histories were
      surveyed. For those who wanted to have their own babies by natural conceptions
      after knowing their karyotypes as well as the risks of abnormal offsprings,
      subsequent pregnancy outcomes were recorded. Total pregnancy outcomes were
      compared between three groups. RESULTS: (1) 503 previous and subsequent
      pregnancies were recorded in detail. The pregnancy outcomes are as follows:
      spontaneous abortions 81.7% (411/503); induced terminations because of fetal
      abnormalities 3.2% (16/503); birth defects 7.2% (36/503); normal/balanced
      offsprings 8.0% (40/503). In reciprocal translocations, nonhomologous
      Robertsonian translocations and homologous Robertsonian translocations, the birth
      defects rates were 5.7% (20/350), 10.9% (14/128) and 8.0% (2/25), respectively (P
      < 0.05). The rates of normal/balanced offsprings in each group were 6.6%
      (23/350), 13.28% (17/128) and 0, respectively (P < 0.05). The rates of
      spontaneous abortions as well as the rates of induced terminations among three
      groups had no statistical differences. (2) Among the 52 congenital defects,
      induced terminations accounted for 30.8% (16/52), and liveborn 69% (36/52).
      Cytogenetic analyses were performed for 27 congenital defects and Down's syndrome
      occupied 59% (16/27). (3) 39 couples with reciprocal or nonhomologous
      Robertsonian translocations gave birth to 40 normal/balanced offsprings, of which
      26 were karyotyped: normal karyotypes were 6 (23%) and balanced translocations 20
      (77%). Couples with homologous Robertsonian translocations had no normal/balanced
      offspring. CONCLUSIONS: Balanced translocation carriers suffer from poor
      pregnancy prognosis. Couples with homologous Robertsonian translocations have
      little chance to give birth to normal/balanced offsprings.

PMID- 17181968
TI  - [Expression of netrin-1 in placenta from patients with pre-eclampsia and the
      relation to placental angiogenesis].
AB  - OBJECTIVE: To investigate the expression of netrin-1 in placenta from patients
      with pre-eclampsia and the relation to placental angiogenesis. METHODS: Twenty
      patients with pre-eclampsia (12 mild cases and 8 severe cases) and 20 normal late
      pregnant women were investigated. The expression of netrin-1 mRNA and protein was
      determined with RT-PCR and Western blotting respectively. The placenta vascular
      density was examined by immunohistochemical F8 staining. RESULTS: (1) The values
      of netrin-1 mRNA in normal group and pre-eclampsia groups were 0.51 +/- 0.08 and
      0.41 +/- 0.06; The values of netrin-1 protein in normal group and pre-eclampsia
      groups were 26.4 +/- 1.8 and 20.5 +/- 1.3 (P < 0.01). The values of netrin-1 mRNA
      in mild and severe pre-eclampsia groups were 0.48 +/- 0.08 and 0.34 +/- 0.07; The
      values of netrin-1 protein in mild and severe pre-eclampsia groups were 22.8 +/-
      1.3 and 18.2 +/- 1.0 (P < 0.01). (2) The placenta vascular density in pre
      eclampsia (54 +/- 8) was significantly reduced than in normal group (65 +/- 10)
      (P < 0.01); the decrease was even more obvious in severe group (48 +/- 7) than in
      mild group (60 +/- 9) (P < 0.01). (3) There was positive correlation between the
      expression of netrin-1 mRNA and protein and placenta vascular density in normal
      pregnancy (r = 0.67 and 0.71, P < 0.01), as well as in pre-eclampsia group (r =
      0.61 and 0.70, P < 0.01), in mild pre-eclampsia group (r = 0.69 and 0.73, P <
      0.01), and in severe pre-eclampsia group (r = 0.71 and 0.75, P < 0.01).
      CONCLUSION: The study shows that the decrease of netrin-1 in placenta of patients
      with pre-eclampsia is one of the possible reasons for the reduction of placenta
      vascular density.

PMID- 17181969
TI  - [Influential factors of systemic lupus erythematosus activity during pregnancy
      and its relationship with pregnancy outcome].
AB  - OBJECTIVE: To investigate the influential factors of systemic lupus erythematosus
      (SLE) activity during pregnancy and their relationship with pregnancy outcome.
      METHODS: A retrospective analysis of the clinical history of 66 pregnant women
      with SLE from 1991 to 2005 was carried out. RESULTS: (1) Those patients with
      unstable status progestation, patients being newly diagnosed with SLE during
      pregnancy or patients irregularly using prednisone became active during
      pregnancy. The disease was active in 32 cases (the active group) and inactive in
      34 cases (the inactive group). (2) Obstetric complications in the active group
      included: 9 cases of preeclampsia, 13 cases of fetal growth restriction (FGR), 7
      cases of therapeutic abortion and 15 cases of premature labor; and the
      corresponding numbers in the inactive group were 1, 5, 1 and 4, respectively. All
      the numbers were significantly different between the two groups (P < 0.05). (3)
      Among all SLE injuries, the lupus nephropathy affected pregnancy mostly. With the
      logistic regression advanced method, we found the lupus nephropathy was the
      independent risk factor for preeclampsia and FGR. (4) The rates of preeclampsia,
      and fetal losses were 4.7% (2/43) and 9.3% (4/43) in the patients taking
      prednisone less than 15 mg/day, and were 33.3% (6/18) and 44.4% (8/18) in the
      patients taking prednisone more than 20 mg/day, being significantly different
      from the former (P < 0.01). CONCLUSIONS: Being unstable progestation, being newly
      diagnosed during pregnancy or irregular prednisone use are important influential
      factors of SLE activity. SLE flares during pregnancy, especially the lupus
      nephropathy correlate closely with the adverse pregnancy outcomes. The rates of
      preeclampsia, and fetal losses increase in the patients taking prednisone more
      than 20 mg/day compared with the patients taking prednisone less than 15 mg/day.

PMID- 17181970
TI  - [Prenatal diagnosis and outcomes of fetuses with cutaneous hemangioma].
AB  - OBJECTIVE: To study the ultrasonic characteristics of fetal cutaneous hemangioma
      and the association with perinatal outcomes. METHODS: Five fetuses with cutaneous
      hemangioma were detected by gray-scale and color Doppler ultrasound, compared
      with the result of pathology and hematology examinations after birth. RESULTS: Of
      the 5 cases diagnosed by ultrasound, 3 had arteriovenous fistulas. In these 3
      cases two fetuses developed high-output cardiac failure, and one developed
      cardiac insufficiency and thrombocytopenia. Finally one fetus was induced, one
      fetus died in the uterus and one neonate survived. The other two fetuses who had
      small tumors diagnosed by ultrasound did not develop any perinatal complications,
      and the neonates had favourable prognosis. CONCLUSIONS: Massive hemangiomas are
      frequently associated with life-threatening complications such as high-output
      heart failure, thrombocytopenia and disseminated intravascular coagulopathy
      (Kasabach-Merritt syndrome).

PMID- 17181971
TI  - [Lymphatic mapping and parametrial lymph nodes identification in patients with
      early stage cervical cancer].
AB  - OBJECTIVE: To determine the presence, distribution, and metastasis incidence of
      parametrial lymph nodes (PLN) of patients with cervical cancer and to investigate
      the role of lymphatic mapping and topographic section in PLN identification.
      METHODS: Sixty patients with early stage (Ib-IIa) cervical cancer undergoing
      radical hysterectomy and pelvic lymphadenectomy were included in the study.
      Before surgery 4 ml methylene was injected into the cervix around the tumor. The
      blue-dyed lymph nodes were identified as sentinel lymph nodes (SLN) during
      operation. An immediate topographic section on uterine specimen was performed to
      separate the PLN from parametria for pathologic examination. RESULTS: Ninety five
      PLN were presented in 38 (63%) of 60 specimens, with a mean size in diameter of
      (0.46 +/- 0.24) cm. Among the total PLN, 57 (60%) were located parallel to
      uterine artery through the entire broad ligament, and the other 38 (40%) were
      scattered in cardinal ligament, sacral ligament and vesicocervical ligament.
      After lymphatic mapping, 69 (73%) of PLN were dyed and identified as SLN.
      Parametrial metastasis was found in 12 (20%) patients, and parametrium was the
      only site containing positive nodes in 2 patients with parametrial metastasis. On
      routine pathologic evaluation, 17 PLN were found to be positive. Among the
      remaining 78 PLN, multilevel sectioning in conjunction with immunohistochemical
      analysis was carried out and 3 PLN containing micrometastases were identified.
      CONCLUSIONS: The study shows that PLN are usually found in the parametria, and
      these nodes often contain metastatic diseases which are easily overlooked.
      Lymphatic mapping followed by meticulous topographic section is feasible in PLN
      identification in patients with cervical cancer.

PMID- 17181972
TI  - [Construction and package of the expression plasmid pAdEasy-1 system encoding the
      human papillomavirus 16 E7 gene and the gene's influence on HeLa cells].
AB  - OBJECTIVE: To investigate the effect of human papillomavirus 16 E7 gene on cell
      cycle of cervical cancer HeLa cell, through construction and expression of human
      papillomavirus 16 E7 gene with adenovirus vector. METHODS: Recombinant adenovirus
      which expressed E7 gene was constructed and packed. Flow cytometry (FCM) was used
      to detect the changes of cell cycle phase and cyclin D1 between cells infected
      and uninfected by recombinant adenovirus. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphennyltetrazolium bromide (MTT) colorimetric assay was used in the detection
      of the alteration of cell growth. RESULTS: The recombinant adenovirus had stable
      efficiency of infection and E7 genes could be expressed stably. The result of MTT
      showed the multiplication of HeLa cells was accelerated from 0.27 +/- 0.03 before
      infection to 0.38 +/- 0.02 after infection (P < 0.01). FCM showed the number of
      cells in S phase increased from (26.0 +/- 0.4)% to (36.0 +/- 2.0)% at 12 hours
      and (49.9 +/- 4.2)% at 24 hours after infection (P < 0.05). Cyclin D1 expression
      was 22.4% before infection, and decreased to 55.2% after infection (P < 0.01).
      CONCLUSIONS: The recombinant adenovirus expressing E7 gene could infect target
      cells. E7 gene can influence cell-cycle of HeLa cells, which can be used to
      restrain cervical cancer.

PMID- 17181984
TI  - Pemetrexed disodium for the treatment of malignant pleural mesothelioma: a
      systematic review and economic evaluation.
AB  - OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of
      pemetrexed disodium in combination with cisplatin for the treatment of
      unresectable pleural mesothelioma in chemotherapy-naive patients. DATA SOURCES:
      Electronic databases were searched up to May 2005. REVIEW METHODS: The systematic
      review was conducted following accepted guidelines. An assessment of the economic
      submission received from the manufacturer of pemetrexed was also carried out.
      This comprised two sections, each employing an economic model. One of these
      models was then reformulated in order to carry out a separate exploration of
      economic performance. RESULTS: One randomised controlled trial comparing
      pemetrexed and cisplatin with cisplatin alone, and involving a total study
      population of 448 patients, met the inclusion criteria. Pemetrexed in combination
      with cisplatin in this trial showed a 2.8-month gain in median survival compared
      with cisplatin alone in an intention-to-treat (ITT) population (12.1 and 9.3
      months, respectively, p = 0.020, hazard ratio of 0.77). During the trial,
      increased reporting of severe toxicity in the pemetrexed arm led to a change in
      the protocol to add folic acid and vitamin B12 supplementation to therapy. For
      fully supplemented patients (n = 331) the hazard ratio for median survival in
      favour of pemetrexed plus cisplatin was also comparable (0.75), but of borderline
      significance between treatment arms (p = 0.051). The trial inclusion criteria
      restricted recruitment to those with a Karnofsky performance status of 70 or
      greater (equivalent to ECOG/WHO 0 or 1 scales more widely used in the UK).
      Quality of life scores using the Lung Cancer Symptom Scale demonstrated
      significantly greater improvement for pain and dyspnoea for patients in the
      combination group compared with those in the cisplatin group. In the ITT
      population, the incidence of serious toxicities with pemetrexed plus cisplatin
      was higher compared with cisplatin alone. However, the grade 3/4 toxicities of
      the combination arm, particularly leucopenia, neutropenia and diarrhoea, were
      found to be greatly improved by the addition of vitamin B12 and folic acid. The
      existing published economic literature was very limited. The economic evaluation
      conducted by the study (and that submitted by the manufacturer) suggested that
      pemetrexed is unlikely to be considered cost-effective at conventionally accepted
      thresholds in the UK for all patients, mainly because of the high cost of
      pemetrexed itself compared with cisplatin. These findings were better for some
      patient subgroups, e.g. especially for fully supplemented (FS) patients with good
      performance status (0/1) and advanced disease (AD). These findings seem robust.
      The estimated cost-effectiveness results were for the FS population, incremental
      cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained =
      pound59,600; for the FS with AD population, ICER per QALY = pound47,600; for the
      FS with performance status 0/1 population, ICER per QALY = pound49,800; and for
      the FS with performance status 0/1 and AD population, ICER per QALY =
      pound36,700. CONCLUSIONS: The new therapy examined in this document demonstrates
      an extension of life expectancy and palliation, as measured by time to
      progression of disease and other end-points. However, the absolute benefit
      obtained is small, and it needs to be weighed against the benefits of effective
      palliative care services. The limited benefit was also at the expense of
      considerable toxicity to patients. The economic evaluation conducted in this
      study and that of the manufacturers suggest that pemetrexed is not cost-effective
      at conventional thresholds for all patients. Cost-effectiveness seems better for
      some patient subgroups, e.g. especially for patients with good performance status
      and with advanced diseases, where it is estimated the ICER per QALY would be
      pound36,700. Given the relatively small number of patients with mesothelioma,
      albeit increasing, the overall budget impact of pemetrexed would be unlikely to
      be more than pound5 million per year at present costs. Much more research is
      needed into the optimum chemotherapy for patients with mesothelioma and a clear
      definition of what constitutes best supportive care.

PMID- 17181985
TI  - A systematic review and economic model of the clinical effectiveness and cost
      effectiveness of docetaxel in combination with prednisone or prednisolone for the
      treatment of hormone-refractory metastatic prostate cancer.
AB  - OBJECTIVES: A systematic review was undertaken and an economic model constructed
      to evaluate the clinical effectiveness and cost-effectiveness of docetaxel
      (Taxotere, Sanofi-Aventis) in combination with prednisone/prednisolone for the
      treatment of metastatic hormone-refractory prostate cancer (mHRPC). The main
      comparators considered were other established chemotherapy regimens and best
      supportive care. DATA SOURCES: Twenty-one resources (including MEDLINE, EMBASE
      and the Cochrane Library) were searched to April 2005. REVIEW METHODS: Two
      reviewers independently assessed studies for inclusion. Data from included
      studies were extracted and quality assessed. Where appropriate, outcomes were
      synthesised using formal analytic approaches. A new economic model was developed
      in order to establish the cost-effectiveness of docetaxel compared with a range
      of potential comparators. A separate review was undertaken to identify sources of
      utility data required to estimate quality-adjusted life-years (QALYs).
      Sensitivity analyses were also undertaken to explore the robustness of the main
      analysis to alternative assumptions related to quality of life. Monte Carlo
      simulation was used to propagate uncertainty in input parameters through the
      model in such a way that the results of the analysis could be presented with
      their uncertainty. The impact of uncertainty surrounding the decision was
      established using value of information and implementation approaches. RESULTS:
      Seven randomised controlled trials were identified that met the inclusion
      criteria. A direct comparison of docetaxel plus prednisone versus mitoxantrone
      plus prednisone in an open-label randomised trial showed improved outcomes for
      docetaxel plus prednisone in terms of overall survival, quality of life, pain and
      prostate-specific antigen decline. Two other chemotherapy regimens that included
      docetaxel: docetaxel plus estramustine and docetaxel plus prednisone plus
      estramustine, also showed improved outcomes in comparison with mitoxantrone plus
      prednisone. Indirect comparison suggested that docetaxel plus prednisone seems to
      be superior to corticosteroids alone in terms of overall survival. Conclusions on
      cost-effectiveness were primarily informed by the results of the in-house model.
      This indicated that mitoxantrone plus a corticosteroid is probably cheaper and
      more effective than corticosteroid alone. Compared with mitoxantrone plus
      prednisone/prednisolone, the use of docetaxel plus prednisone/prednisolone (3
      weekly) appears cost-effective only if the NHS is prepared to pay 33,000 pounds
      per QALY. The incremental cost-effectiveness ratio associated with docetaxel plus
      prednisone (3-weekly) remained fairly robust to these variations with estimates
      ranging from 28,000 pounds to 33,000 pounds per QALY. Value of information
      analysis revealed that further research is potentially valuable. Given a maximum
      acceptable ratio of 30,000 pounds per QALY, the expected value of information was
      estimated to be approximately 13 million pounds. CONCLUSIONS: This systematic
      review of the research suggests that docetaxel plus prednisone seems to be the
      most effective treatment for men with mHRPC. The economic model suggests that
      treatment with docetaxel plus prednisone/prednisolone is cost-effective in
      patients with mHRPC provided the NHS is prepared to pay 33,000 pounds per
      additional QALY. Future research should include the direct assessment of quality
      of life and utility gain associated with different treatments, including the
      effect of adverse events of treatment, using generic instruments, which are
      suitable for the purposes of cost-effectiveness analyses.

PMID- 17181986
TI  - Iron Overload (with Attention to Genetic Testing and Diagnosis/Management of HFE
      Wild Type Patients).
AB  - The discovery of the HFE, HJV, HAMP, TfR2, and SLC40A1 genes and preliminary
      understanding of their roles in iron homeostasis have contributed tremendously to
      our understanding of the pathogenesis of genetic hemochromatosis. Although
      several new models of iron metabolism have been proposed, some key "sensor" steps
      of iron absorption in the enterocytes and of iron storage in hepatocytes and
      other cells remain unclear. A diagnosis of non-HFE genetic hemochromatosis should
      be considered in patients with unexplained iron overload who do not have the
      common mutations in the HFE genes. Phenotypic evaluation such as liver biopsy and
      measurement of hepatic iron concentration remain important in non-HFE
      hemochromatosis because mutations in other genes are rare and there are no other
      available noninvasive tests to confirm the diagnosis. Phlebotomy remains the
      mainstay of therapy also for non-HFE hemochromatosis. However, phlebotomy may not
      be well tolerated in certain forms of non-HFE hemochromatosis such as
      "ferroportin disease."

PMID- 17181987
TI  - Animal models for human metapneumovirus (HMPV) infections.
AB  - Since its detection in 2001 the human Metapneumovirus (HMPV), a member of the
      Paramyxoviridae family, was observed to be a serious pathogen in human
      respiratory infections during childhood. Meanwhile, several animal models have
      been established to study the virus-host interactions and pathogenic effects.
      Mainly, small laboratory animals like mice and cotton rats have been used,
      although the usage of these two species for HMPV research is controversially
      discussed and contradictious results were obtained by different groups. Further
      trials with ferrets, hamsters and non human primates were performed revealing
      different success in their individual usage. In this review we present the
      different animal models, summarize their advantages and disadvantages, and
      discuss the controversial results from different studies.

PMID- 17181988
TI  - Propagation of scrapie in peripheral nerves after footpad infection in normal and
      neurotoxin exposed hamsters.
AB  - As is known from various animal models, the spread of agents causing
      transmissible spongiform encephalopathies (TSE) after peripheral infection
      affects peripheral nerves before reaching the central nervous system (CNS) and
      leading to a fatal end of the disease. The lack of therapeutic approaches for TSE
      is partially due to the limited amount of information available on the
      involvement of host biological compartments and processes in the propagation of
      the infectious agent. The in vivo model presented here can provide information on
      the spread of the scrapie agent via the peripheral nerves of hamsters under
      normal and altered axonal conditions. Syrian hamsters were unilaterally footpad
      (f.p.) infected with scrapie. The results of the spatiotemporal ultrasensitive
      immunoblot-detection of scrapie-associated prion protein (PrP(Sc)) in serial
      nerve segments of both distal sciatic nerves could be interpreted as a
      centripetal and subsequent centrifugal neural spread of PrP(Sc) for this route of
      infection. In order to determine whether this propagation is dependent on main
      components in the axonal cytoskeleton (e.g. neurofilaments, also relevant for the
      component ;a' of slow axonal transport mechanisms), hamsters were treated -in an
      additional experiment- with the neurotoxin beta,beta-iminodiproprionitrile (IDPN)
      around the beginning of the scrapie infection. A comparison of the Western blot
      signals of PrP(Sc) in the ipsilateral and in the subsequently affected
      contralateral sciatic nerve segments with the results revealed from IDPN
      untreated animals at preclinical and clinical stages of the TSE disease,
      indicated similar amounts of PrP(Sc). Furthermore, the mean survival time was
      unchanged in both groups. This in vivo model, therefore, suggests that the
      propagation of PrP(Sc) along peripheral nerves is not dependent on an intact
      neurofilament component of the axonal cytoskeleton. Additionally, the model
      indicates that the spread of PrP(Sc) is not mediated by the slow component ;a' of
      the axonal transport mechanism.

PMID- 17181989
TI  - Prevalence of Helicobacter pylori cagA, iceA and babA2 alleles in Brazilian
      patients with upper gastrointestinal diseases.
AB  - Helicobacter pylori is an important human pathogen associated with
      gastrointestinal diseases such as gastritis, gastric and duodenal ulcer (peptic
      ulcer disease, PUD), and gastric cancer. A number of pathogenic factors have been
      described for this bacterium, and some of them have been proposed as markers for
      the prediction of the clinical outcome. However, with the exception of the cag
      and vacA status, there is no universal consensus regarding the importance of the
      other virulence factors. Therefore, the aim of this study was to investigate the
      status of H. pylori strains regarding the babA and iceA alleles, as well as the
      cagA genotype, to reveal any association between these genotypes and clinical
      outcomes in Brazilian patients. The great majority (92.6%) of the strains were
      typed as iceA1, while 40.4% were found to possess the babA2 allele. The cagA gene
      was detected in 73.4% of the strains. The iceA2 and cagA genotypes were
      associated with PUD, while iceA1 was negatively correlated with PUD. However,
      considering the high percentage of strains typed as iceA1, these associations
      must be treated with caution. No clinical entity was associated with the babA2
      allele. These results suggest that iceA1 is not a good marker for the diseases
      associated with H. pylori infection in Brazil. Further studies are needed in
      order to elucidate the relevance of the babA status, because other studies
      performed in Brazil have associated the babA2 allele with clinical outcomes.
      These results also indicate the existence of regional differences in the H.
      pylori genotypes and their association with clinical outcomes.

PMID- 17181990
TI  - Analysis of 2'-O-methylated nucleosides and pseudouridines in ribosomal RNAs
      using DNAzymes.
AB  - Ribosomal RNAs (rRNAs) contain a large number of posttranscriptionally modified
      nucleosides, the physiological function of which is still unclear. The great
      majority of modifications in eukaryotes and archaea are 2'-O-ribose methylated
      nucleosides and pseudouridines. The current methods to identify rRNA
      modifications are difficult to perform and need expensive reagents. Here we
      report an easy method to detect 2'-O-ribose methylations using RNA-cleaving
      deoxyribozymes (DNAzymes) and demonstrate its application using rRNA of the yeast
      Saccharomyces cerevisiae. Using DNAzymes of the 10-23 type, we could show that
      cleavage at A(973) in the 18S rRNA or at G(1450) in the 25S rRNA from S.
      cerevisiae occurs only if the 2'-O-ribose methylations at these positions were
      missing. We also designed 8-17-DNAzymes for the detection of 2'-O-ribose
      methylations. This makes all 2'-O-ribose methylations accessible to the DNAzyme
      technique as variants of the 8-17-DNAzyme that together have the ability to
      cleave nearly any dinucleotide junction are known. Furthermore, we found that
      pseudouridine also decreases the DNAzyme cleavage efficiency at the adjacent
      phosphodiester bond and thus can also be identified with DNAzymes. The analysis
      using DNAzymes provides a new tool to easily identify ribose methylations in
      rRNAs and will help to unravel the physiological function of nucleotide
      modifications.

PMID- 17181991
TI  - Thermostable red and green light-producing firefly luciferase mutants for
      bioluminescent reporter applications.
AB  - Light emission from the North American firefly Photinus pyralis, which emits
      yellow-green (557-nm) light, is widely believed to be the most efficient
      bioluminescence system known, making this luciferase an excellent tool for
      monitoring gene expression. We present studies on the production of a set of
      thermostable red- and green-emitting luciferase mutants with bioluminescent
      properties suitable for dual-color reporter assays, biosensor measurements with
      internal controls, and imaging techniques. Starting with the luciferase variant
      Ser284Thr, we introduced the mutations Thr214Ala, Ala215Leu, Ile232Ala,
      Phe295Leu, and Glu354Lys to produce a new red-emitting enzyme with a
      bioluminescence maximum of 610 nm, narrow emission bandwidth, favorable kinetic
      properties, and excellent thermostability at 37 degrees C. By adding the same
      five changes to luciferase mutant Val241Ile/Gly246Ala/Phe250Ser, we produced a
      protein with an emission maximum of 546 nm, providing a set of thermostable
      enzymes whose bioluminescence maxima were separated by 64 nm. Model studies
      established that the luciferases could be detected at the attomole level and six
      orders of magnitude higher. In microplate luminometer format, mixtures containing
      1.0 fmol total luciferase were quantified from measurements of simultaneously
      emitted red and green light. The results presented here provide evidence that it
      is feasible to monitor two distinct activities at 37 degrees C with these novel
      thermostable proteins.

PMID- 17181992
TI  - Sedimentation velocity analytical ultracentrifugation and SEDFIT/c(s): limits of
      quantitation for a monoclonal antibody system.
AB  - Sedimentation velocity analytical ultracentrifugation (SV-AUC) has emerged in the
      biopharmaceutical industry as a technique to detect small quantities of protein
      aggregates. However, the limits of detection and quantitation of these aggregates
      are not yet well understood. Although diverse factors (molecule, instrument,
      technique, and software dependent) preclude an all-encompassing measurement of
      these limits for the complete system, it is possible to use simulated data to
      determine the quantitation limits of the data analysis software aspect. The
      current study examines the performance of the SEDFIT/c(s) data analysis tool with
      simulated antibody monomer/dimer and monomer/aggregate systems. Under completely
      ideal conditions (zero noise, known meniscus, and shape factor homogeneity), the
      software limit of quantitation was 0.01% for the monomer/aggregate system and
      0.03% for the less well-resolved monomer/dimer system. Under more realistic
      conditions (0.005 OD root mean square [RMS] noise, shape factor variability, and
      long solution column), the software limits of quantitation were 0.2 and 0.6%
      (0.002 and 0.006 OD) for the monomer/aggregate and monomer/dimer systems,
      respectively. Interestingly, diminished quantitation accuracy at very low levels
      of oligomer was not accompanied by deterioration of fit quality (as measured by
      root mean square deviation [RMSD] and residuals bitmap images).

PMID- 17181993
TI  - On the use of ratio standard curves to accurately quantitate relative changes in
      protein levels by Western blot.

PMID- 17181994
TI  - Methods for the quantitation of human milk oligosaccharides in bacterial
      fermentation by mass spectrometry.
AB  - Oligosaccharides are the third most abundant component in human milk. In the past
      decades, it became apparent that they would be able to protect against pathogens
      and participate in the development of the gut microflora for infants. However,
      their role in infants' nutrition and development remains poorly understood. To
      better understand this function, it is extremely important to have a quantitative
      tool for profiling oligosaccharides. In this article, we show the development of
      a method to quantitatively differentiate the relative amounts of oligosaccharides
      fermented by different intestinal bacteria. To determine the oligosaccharide
      consumption, bacteria were grown in a medium using human milk oligosaccharides
      (HMOs) as the only carbon source purified from breast milk and further analyzed
      by matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron
      resonance mass spectrometry (MALDI-FTICR MS). A method using an internal
      deuterium-labeled standard was developed and compared with an external standard
      method, with the internal standard method giving better precision and unambiguous
      measurements than the external standard method and providing to be a novel and
      robust tool for following bacterial fermentation of milk oligosaccharides.

PMID- 17181995
TI  - A cross-sectional study of self-reported back and neck pain among English
      schoolchildren and associated physical and psychological risk factors.
AB  - This study set out to identify the associations between ergonomics and other
      factors with back and neck pain among schoolchildren. Self-reported
      questionnaires were used to record health outcomes and potential risk factors in
      state schools. Six hundred and seventy-nine schoolchildren from Surrey in the
      United Kingdom aged 11-14 years took part. Twenty-seven percent of children
      reported having neck pain, 18% reported having upper back pain, and 22% reported
      having low back pain. A forward stepwise logistic regression was performed with
      pain categories the dependent variables. Neck pain was significantly associated
      with school furniture features, emotional and conduct problems, family history of
      low back pain and previous treatment for musculoskeletal disorders. Upper back
      pain was associated with school bag weight (3.4-4.45 kg), school furniture
      features, emotional problems and previous treatment for musculoskeletal
      disorders. Low back pain was associated with school furniture features, emotional
      problems, family history and previous injury or accident. It is important to
      recognise the influence of physical, psychological and family factors in
      children's pain.

PMID- 17181996
TI  - Modulation of hypotensive effects of kinins by cathepsin K.
AB  - Kinins are pro-inflammatory peptides, which participate in the maintenance of
      cardiovascular homeostasis, and play a key role in numerous diseases, including
      lung fibrosis and hypertension. Evidence has been provided recently for the
      presence of alternative mechanisms of bradykinin generation and/or degradation.
      Here we showed that cathepsin K may act as a potent kinin-degrading enzyme in
      bloodstream. Contrary to cathepsin L, cathepsin K attenuates kallikrein-induced
      decrease of rat blood pressure, and reduces the hypotensive effect of bradykinin
      in a dose-dependent manner. Moreover, we identified, by engineering the S2
      subsite of both recombinant enzymes, two critical residues involved respectively
      in the kininase activity of cathepsin K, i.e. Tyr67/Leu205, versus kininogenase
      activity of cathepsin L, i.e. Leu67/Ala205. In conclusion, according to its
      ability to modulate hypotensive effects of kinins, we propose that cathepsin K is
      a kininase of biological relevance, in complement of well-documented neutral
      endopeptidase or angiotensin-converting enzyme.

PMID- 17181997
TI  - The effect of epidermal growth factor on matrix metalloproteinases and tissue
      inhibitors of metalloproteinase gene expression in cultured human gingival
      fibroblasts.
AB  - OBJECTIVE: Matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs) play a role in the breakdown of the extracellular
      matrix during normal physiological processes, and in pathological processes,
      including periodontitis. The aim of this study was to evaluate the effect of
      epidermal growth factor (EGF) on the expression of MMPs and TIMPs in cultured
      human gingival fibroblasts. METHODS: Fibroblasts were stimulated with 10(-3), 10(
      6) or 10(-12)M EGF for 24h; untreated fibroblasts served as controls. Alterations
      in the expression of MMP-1, 2, 3, 7, 11, TIMP-1 and 2 were evaluated using real
      time PCR and Western blotting. beta-Actin expression was used as a reference to
      normalize gene expression. RESULTS: Increased MMP-1, 3, 7 and 11 expressions were
      observed at all EGF concentrations (p<0.05). At the lowest EGF concentration, MMP
      1, 3 and 7 presented the lowest expression and MMP-11 presented the greatest
      expression; at higher EGF concentrations, MMP-1, 3 and 7 presented greater up
      regulation, and MMP-11 lower up-regulation (p<0.05). Protein expression was
      similarly regulated by EGF: increased up-regulation of MMP-1, 3 and 7 was
      observed with increasing EGF concentrations, except for MMP-11 that exhibited
      greater up-regulation at the lower EGF concentration. The gene expression of MMP
      2, TIMP-1 and 2 was not affected by EGF (p<0.05). CONCLUSIONS: We conclude that
      EGF regulates expression for MMP-1, 3, 7 and 11 in a dose-dependent manner,
      suggesting that EGF may play a role in periodontal destruction and wound repair.

PMID- 17181998
TI  - Micromorphological and micronanalytical characterization of stagnating and
      progressing root caries lesions.
AB  - Root caries is the predominant disease of the tooth tissues in the elderly
      population and differs in progression and micromorphology from coronal dentin
      caries. Therefore, different clinical concepts are needed for the treatment of
      these progressing and arrested lesions. It was the aim of this study to
      investigate the three-dimensional structure and volume of stagnating and
      progressing root caries lesions and to determine the mineral composition of the
      different lesion zones to achieve a better understanding of the natural history
      of root caries lesion formation. Of 21 extracted human teeth of patients between
      42 and 77 years of age with stagnating and progressing root caries lesions serial
      sections were cut and investigated with polarized light and scanning electron
      microscopy. From the polarized light micrographs 3D reconstructions were made to
      determine the volumes of the lesion zones and their relations expressed in a
      demineralization index (DI). With increasing size of the demineralizing zone the
      DI increased indicating an increase in the size of the translucent zone. The 3D
      reconstructions showed distinct differences between stagnating and progressing
      root caries lesions. In the hypermineralized translucent dentin not all dentin
      tubules were obliterated by intratubular dentin and within the translucent dentin
      scattered dead tracts were found. Electron dispersive X-ray (EDX) analysis showed
      that the intertubular dentin of the translucent dentin was also demineralized to
      a certain extent. The results indicate distinct morphological differences between
      progressing and stagnating root caries lesions which may have consequences for
      treatment strategies.

PMID- 17181999
TI  - Responding to symptoms of depression and anxiety: emotion regulation,
      neuroticism, and engagement in risky behaviors.
AB  - The current study examined whether neuroticism, emotional regulation deficits,
      and/or their interaction predict increased engagement in risky behaviors
      following increases in symptoms of depression or anxiety over the course of 6
      weeks. Results of hierarchical linear modeling analyses indicated that
      individuals who exhibited high levels of both neuroticism and emotional
      regulation deficits were more likely than other individuals to report increased
      engagement in risky behaviors following increases in symptoms of either
      depression or anxiety. Unexpectedly, individuals who exhibited high levels of
      neuroticism and adaptive emotion regulation strategies exhibited decreased
      engagement in risky behaviors following increases in depressive or anxious
      symptoms.

PMID- 17182000
TI  - The ColE2-P9 Rep protein binds to the origin DNA as a monomer.
AB  - The Rep proteins of some plasmid replicons have two functions. Dimers bind to the
      operator sequences acting as auto-repressors, whereas monomers bind to the
      iterons to initiate replication of DNA. The ColE2 Rep proteins are present mostly
      in a dimeric form with some multimers larger than dimers in solution, while the
      form of Rep binding to Ori is not known. We used an EMSA-based method to
      determine the molecular weight of Rep in the Rep-Ori complex. The result
      suggested that Rep binds to Ori as a monomer. In addition, the result of EMSA
      using the Rep protein fused with the maltose binding protein and the His6-tag
      also supported this conclusion. We proposed that dimerization of Rep might
      probably be involved in keeping the copy number of the ColE2 plasmid at the
      normal low level by limiting the amount of active monomeric forms of Rep in the
      host cell.

PMID- 17182002
TI  - HDJC9, a novel human type C DnaJ/HSP40 member interacts with and cochaperones
      HSP70 through the J domain.
AB  - HSP40s are a subfamily of heat shock proteins (HSPs) and play important roles in
      regulation of cell proliferation, survival and apoptosis by serving as chaperones
      for HSP70s. Up to date hundreds of HSP40 proteins derived from various species
      ranging from Escherichia coli to homo sapiens have been identified. Here we
      report the cloning and characterization of a novel human type C DnaJ homologue,
      HDJC9, containing a typical N-terminal J domain. HDJC9 is upregulated at both
      mRNA and protein levels upon various stress and mitogenic stimulations. HDJC9 is
      mainly localized in cell nuclei under normal culture conditions while it is
      transported into cytoplasm and plasma membrane upon heat shock stress through a
      non-classical and lipid-dependent pathway. HDJC9 can interact with HSP70s and
      activate the ATPase activity of HSP70s, both of which are dependent on the J
      domain. Our data suggest that HDJC9 is a novel cochaperone for HSP70s.

PMID- 17182001
TI  - GSK3beta positively regulates Hedgehog signaling through Sufu in mammalian cells.
AB  - Hedgehog signaling plays important roles in embryonic patterning of multicellular
      organisms. This pathway is ultimately transmitted by the zinc-finger
      transcriptional factor Gli, of which activity is suppressed by Sufu, a negative
      regulator of this signaling. To clarify this regulation to more detail, we
      screened for Sufu-binding proteins. We identified GSK3beta as a specific binding
      partner of Sufu by mass spectrometric analysis. GSK3beta bound to Sufu both in
      vitro and in vivo. Down-regulation of GSK3beta expression by RNAi in Hedgehog
      responsive cells attenuated Hedgehog signaling, suggesting that GSK3beta
      functions as a positive regulator of Hedgehog signaling. In addition, an in vitro
      kinase assay showed that GSK3beta phosphorylates Sufu and phosphorylation
      mimicking mutant of Sufu showed significantly decreased ability to bind Gli1 and
      could not suppress the Gli-mediated expression of a reporter gene efficiently.
      These results strongly suggest that GSK3beta phosphorylates Sufu to positively
      regulate Hedgehog signaling in mammalian cells.

PMID- 17182003
TI  - Characterization of the plant homolog of Nijmegen breakage syndrome 1:
      Involvement in DNA repair and recombination.
AB  - The Nbs1 gene is known to code for a protein involved in the hereditary cancer
      prone disease, Nijmegen breakage syndrome. This gene is conserved in animals and
      fungi, but no plant homolog is known. The work reported here describes a homolog
      of Nbs1 isolated from higher plants. The Nbs1 proteins from both Arabidopsis
      thaliana and Oryza sativa are smaller in size than animal or yeast Nbs1, but both
      contain the conserved Nbs1 domains such as the FHA/BRCT domain, the Mre11-binding
      domain, and the Atm-interacting domain in orientations similar to what is seen in
      animal Nbs1. The OsNbs1 protein interacted not only with plant Mre11, but also
      with animal Mre11. In plants, OsNbs1 mRNA expression was found to be higher in
      the shoot apex and young flower, and AtNbs1 expression increased when plants were
      exposed to 100 Gy of X-rays. These results suggest that plant Nbs1 could
      participate in a Rad50/Mre11/Nbs1 complex, and could be essential for the
      regulation of DNA recombination and DNA damage responses.

PMID- 17182004
TI  - The induction mechanism of the molecular chaperone HSP70 in the gastric mucosa by
      Geranylgeranylacetone (HSP-inducer).
AB  - To elucidate the induction mechanism of HSP70 by geranylgeranylacetone (GGA), we
      investigated GGA specific binding proteins using a GGA-affinity column.
      Alteration of chaperone activity of HSP70 and binding affinity of HSP70 to heat
      shock factor-1 (HSF-1) was evaluated in the presence or absence of GGA. The
      binding domain of HSP70 to GGA was also analyzed. A 70-kDa protein eluted by 10
      mM GGA from the GGA-affinity column was identical to constitutively expressed
      HSP70 on immunoblotting. GGA-binding domain of HSP70 was C-terminal of the
      protein as peptide-binding domain (HSP70C). The chaperone activity of HSP70 and
      recombinant HSP70C was suppressed by GGA. Furthermore, dissociation of the HSP70
      from HSF-1 was observed in the presence of GGA. GGA preferentially binds to the C
      terminal of HSP70 which binds to HSF-1. After dissociation of HSP70, free HSF-1
      could acquire the ability to bind to HSE (the promoter region of HSP70) gene.

PMID- 17182005
TI  - GST M1/T1 and MTHFR polymorphisms as risk factors for hypertension.
AB  - The aim of this study is to investigate GSTM1, GSTT1 and MTHFR genetic
      polymorphisms and its relation with total plasma glutathione (tGSH) levels in
      hypertension. Genotype distributions of GSTM1 and GSTT1 deletion polymorphisms
      and C677T variant of MTHFR were examined in a sample of 94 hypertensive patients
      with congestive heart failure and 207 healthy unrelated Portuguese individuals
      using PCR techniques. Plasma GST activity was determined spectrophotometrically.
      The antioxidant status was evaluated by fluorometric assays of tGSH. Genotype
      distributions of GSTT1 (chi2 test; p < 0.01) and MTHFR (chi2 test; p < 0.01)
      differ significantly between control and hypertensive patients with a greater
      prevalence of "non-null GSTT1/M1" and CT (heterozygous) genotypes. Moreover, GST
      activity and tGSH were markedly decreased in hypertension but there is no
      correlation with the studied polymorphisms. GSH depletion confirmed the possible
      involvement of oxidative stress in this pathology. Deletion of GSTT1 gene might
      be considered as protective factor for hypertension.

PMID- 17182006
TI  - Hexachlorobenzene as hormonal disruptor--studies about glucocorticoids: their
      hepatic receptors, adrenal synthesis and plasma levels in relation to impaired
      gluconeogenesis.
AB  - In Wistar rats, hexachlorobenzene (HCB) depresses the gluconeogenic enzyme
      phosphoenolpyruvate-carboxykinase (PEPCK). In the liver, glucocorticoids (GC)
      normally regulate the glucose synthesis by acting on PEPCK. Thus, the aim of this
      work was to investigate, in a time-course study, the effects of HCB on plasma GC,
      its adrenal synthesis and stimulation, and the kinetic parameters of its hepatic
      receptors (GR) in relation to the gluconeogenic blockage produced by HCB. Plasma
      corticosterone (CORT) concentration, urinary porphyrins and hepatic PEPCK were
      determined after 2, 4, 6 and 8 weeks of HCB-treatment. The effect of HCB on
      kinetic parameters of GR was studied in adrenalectomized porphyric rats after 2,
      4 and 8 weeks of treatment. Additionally, adrenal CORT synthesis in the same
      weeks was measured with or without ACTH. Results show that plasma CORT in
      intoxicated animals dropped significantly after 2 and 4 weeks of treatment (23%
      and 58%, respectively), and then remained constant until the 8th week. HCB also
      promoted a reduction in the number of hepatic GR (50-55%) without modifying
      affinity. After 8 weeks, when porphyria was well established (40-50-fold increase
      in urinary porphyrins), a reduction (52%) in hepatic GR number, as well as a
      decrease in PEPCK activity (56%) were observed. Moreover, CORT biosynthesis in
      adrenals from intoxicated animals significantly decreased (60%) without changes
      in ACTH effect. Briefly, this paper shows that HCB causes a disruption in GC and
      GR. This disturbance could contribute to the negative effect on glucose synthesis
      through PEPCK regulation, thus modulating porphyria. These results enhance the
      knowledge about the hormonal disruption produced by chlorinated xenobiotics.

PMID- 17182007
TI  - Protective effect of baicalein against endotoxic shock in rats in vivo and in
      vitro.
AB  - Dried roots of Scutellaria baicalensis Georgi (Huang qin) are widely used in
      traditional Chinese medicine. Baicalein is a major bioactive flavonoid component
      of H. qin that shows a wide range of biological activities, including antioxidant
      and anti-inflammatory actions. We evaluated therapeutic effects and possible
      mechanisms of action of baicalein on circulatory failure and vascular dysfunction
      during sepsis induced by lipopolysaccharide (LPS; 10 mg/kg, i.v.) in anesthetized
      rats. Treatment of the rats with baicalein (20 mg/kg, i.v.) significantly
      attenuated the deleterious hemodynamic changes of hypotension and tachycardia
      caused by LPS and significantly inhibited the elevation of plasma tumor necrosis
      factor alpha (TNF-alpha). Baicalein also decreased levels of inducible nitric
      oxide synthase (iNOS) and the overproduction of NO and superoxide anions caused
      by LPS. It also increased the survival rate of ICR mice (25-30 g) challenged by
      LPS (60 mg/kg). Moreover, infiltration of neutrophils into the liver and lungs of
      rats 6h after treatment with LPS was also reduced by baicalein. To investigate
      the mechanism of action of baicalein on sepsis, RAW 264.7 cells were used as a
      model. Baicalein inhibited iNOS protein production, and suppressed LPS-induced
      degradation of IkappaBalpha, the formation of a nuclear factor kappa B (NF
      kappaB)-DNA complex and NF-kappaB-dependent reporter gene expression. Thus, the
      therapeutic effects of baicalein were associated with reductions in TNF-alpha and
      superoxide anion levels during sepsis. The inhibitory effects of baicalein on
      iNOS production may be mediated by inhibition of the activation of NF-kappaB.
      Baicalein may thus prove a potential agent against endotoxemia.

PMID- 17182008
TI  - Effect of agmatine on brain L-citrulline production during morphine withdrawal in
      rats: a microdialysis study in nucleus accumbens.
AB  - Agmatine, an endogenous nitric oxide (NO) synthase inhibitor and ligand for
      imidazoline receptors, has been previously shown to prevent morphine dependence
      in rats. The present study was designed to investigate NO formation in nucleus
      accumbens core region (NAcc) during naloxone (NL)-precipitated morphine
      withdrawal in rats treated with agmatine or l-NAME by using intracerebral
      microdialysis in freely moving rats, through measuring extracellular l-citrulline
      concentrations, an indirect sign of NO production since equal amounts of l
      citrulline and NO are produced from l-arginine. l-Citrulline levels in the NAcc
      core did not change following administration of agmatine (40 mg/kg i.p.) or l
      NAME (100 mg/kg i.p.) in control rats. Both agmatine and l-NAME attenuated
      withdrawal symptoms of morphine in NL (2 mg/kg i.p.)-precipitated withdrawal. l
      Citrulline levels showing the release of NO increased in morphine-dependent rats
      during NL-precipitated withdrawal. Agmatine and l-NAME treatments significantly
      suppressed the increase in l-citrulline levels compared to physiological saline
      treated rats in this setting. The results suggest that the release of l
      citrulline in NAcc may be involved in the processes of morphine withdrawal and
      agmatine as an endogenous inhibitor of NO synthase may be one of the factors
      involved in the changes in the physiology and behavioral state during opioid
      withdrawal and may have pharmacological importance.

PMID- 17182009
TI  - RT-PCR-based analysis of microRNA (miR-1 and -124) expression in mouse CNS.
AB  - More than 700 microRNAs (miRNAs) have been cloned, and the functions of these
      molecules in developmental timing, cell proliferation, and cancer have been
      investigated widely. MiRNAs are analyzed with Northern blot and sequential colony
      evaluation; however, reverse transcription-polymerase chain reaction (RT-PCR)
      based miRNA assay remains to be developed. In this report, we describe improved
      real-time RT-PCR methods using specific or non-specific RT primer for the semi
      quantitative analysis of miRNA expression. The use of the new methods in a model
      study revealed differential expression of miRNA-1 (miR-1) and miR-124 in mouse
      organs. Specifically, our methods revealed that miR-124 concentrations in the
      mouse central nervous system (CNS; cerebral cortex, cerebellum, and spinal cord)
      were more than 100 times those in other organs. By contrast, miR-1 expression in
      the CNS was 100-1000 times lower than that in skeletal muscle and heart.
      Furthermore, we revealed anatomically regional differences in miR-124 expression
      within the CNS: expression ratios versus the cerebral cortex were 60.7% for the
      cerebellum and 35.4% for the spinal cord. These results suggest that our RT-PCR
      based methods would be a powerful tool for studies of miRNA expression that is
      associated with various neural events.

PMID- 17182010
TI  - Relationships between neurons expressing neuronal nitric oxide synthase, degree
      of microglia activation and animal survival. A study in the rat cortex after
      transient ischemia.
AB  - The focal ischemia obtained in an animal model of middle cerebral artery
      occlusion (MCAo) causes the "core" of damage in the striatum and the "penumbra"
      of damage in the fronto-parietal cortex. The latter is mainly functionally
      affected and shows changes in nNOS and iNOS expression during the acute phase of
      ischemia. With the aim to study possible relationships between these changes and
      the affection entity during the animal recovery, we investigated from 24 up to
      144 h after reperfusion the expression and content of these two NOS isoforms in
      the neurons and microglia and the degree of microglia reactivity in the fronto
      parietal cortices of rats undertaken to transient MCAo. Evaluation of motor
      sensory performances and survival allowed dividing the animals into two groups.
      Immunohistochemistry, western blot and quantitative analysis demonstrated, both
      in the ischemic and contralateral cortex of the rats with longer survival,
      wellness and significantly increased number of the nNOS-IR neurons at 24 h and
      moderately activated microglia up to 144 h. In the rats not recovering, injured
      and significantly decreased nNOS-IR neurons, intensely activated microglia and
      appearance of iNOS-IR were seen at all time points. In conclusion, since the
      recovery occurs when nNOS-IR neurons are greatly increased, we presume nNOS
      protect the tissue likely controlling the passage from the state of reactive to
      that of activated microglia. Moreover, the morphological signs of wellness and
      the two-fold increase in number of the nNOS-IR neurons appear to be
      characteristic of the "penumbra" area and could explain why this region is mainly
      functionally affected.

PMID- 17182011
TI  - Determining language laterality by fMRI and dichotic listening.
AB  - For imaging studies on hemispheric specialization of the human brain, data about
      known functional asymmetries other than handedness would be valuable for a
      reliable interpretation of lateralized activation in individuals or groups of
      subjects. As certain aspects of language processing are observed to be a function
      of primarily the left, it can be used as a reference for other asymmetric
      processes such as sensory or cognitive skills. For analyzing language laterality,
      there are a variety of methods, but these differ in application or accuracy. In
      this study, we tested the reliability of two widely used methods - dichotic
      listening and fMRI - to determine language dominance in 30 individual subjects.
      The German adaptation of a dichotic listening test (Hattig, H., Beier, M., 2000.
      FRWT: a dichotic listening test for clinical and scientific contexts, Zeitschr f
      Neuropsychologie 11. 233-245.) classified 54% of the 26 right-handed subjects as
      left hemispheric dominant. The results of the fMRI paradigm (Fernandez, G., de
      Greiff, A., von Oertzen, J., et al., 2001. Language mapping in less than 15 min:
      real-time functional MRI during routine clinical investigation. Neuroimage 14,
      585-594.) tested on the same subjects, however, classified 92% of the right
      handed subjects as left dominant. The main reason for this discrepancy was that
      the ear dominance score of many subjects in the dichotic listening test was too
      low to determine a reliable ear advantage. As a consequence, this specific
      dichotic listening test cannot be used to determine language laterality in
      individual subjects. On the other hand, the fMRI results are consistent with
      numerous studies showing left dominant language processing in more than 90% of
      right-handers. In some subjects, however, language laterality critically depends
      on the areas used to determine the laterality index.

PMID- 17182012
TI  - Immunohistochemical localization of dopamine receptor subtypes (D1R-D5R) in
      Alzheimer's disease brain.
AB  - Among the neurotransmitter abnormalities that have been investigated in
      Alzheimer's disease (AD), deficits in the cholinergic system have been the most
      intensively studied. Another key neurotransmitter system involved with emotion
      and cognition is the dopaminergic system. Here we have investigated alterations
      in all five dopamine receptor subtypes in AD brain. Using antipeptide rabbit
      antibodies for each of the five dopamine receptors (D1-D5) we mapped the
      distribution of these receptors in postmortem AD and age-matched control brains
      in the frontal cortex, utilizing biotin-avidin immunocytochemistry. All five DR
      subtypes were expressed as cell surface and cytoplasmic proteins. Receptor
      specific changes in control and AD brain were identified as follows: D4R and D3R
      were the predominant receptor subtypes in age-matched controls followed by D2R
      and D1R; D5R is the least expressed receptor subtype. In AD brain, D2R and D5R
      are well expressed in comparison to D1R, D3R and D4R. Expression of D1R, D3R and
      D4R was severely reduced in AD cortex. D2R expression is moderately reduced in
      the frontal cortex of AD brain. D5R is the only receptor subtype whose expression
      is increased in AD frontal cortex. Furthermore, in AD, we found comparable
      expression of D3R in astrocytes, whereas D5R-like immunoreactivity is
      significantly increased in astrocytes, in comparison to normal frontal cortex,
      where it was predominantly neuronal. These results demonstrate subtype-specific
      changes in dopamine receptors in AD that may be important in disease
      pathophysiology and that may also serve as potential targets for therapeutic
      intervention in AD.

PMID- 17182014
TI  - Enantioselective epoxidation of non-functionalized alkenes using carbohydrate
      based salen-Mn(III) complexes.
AB  - Three new salen ligands with carbohydrate moieties were prepared from a
      salicylaldehyde derivative obtained by reaction of 1,2:5,6-di-O-isopropylidene
      alpha-D-glucofuranose with 3-tert-butyl-5-(chloro-methyl)-2-hydroxybenzaldehyde.
      These ligands were coordinated with Mn(III) to give three chiral salen-Mn(III)
      complexes. The complexes were characterized and employed in the asymmetric
      epoxidation of unfunctionalized alkenes. Catalytic results showed that although
      there are no chiral groups on the diimine bridge, these complexes had some
      enantioselectivity, which indicates the carbohydrate moiety has an asymmetric
      inducing effect in the epoxidation reaction.

PMID- 17182015
TI  - Structural determination of the O-antigenic polysaccharide from Escherichia coli
      O166.
AB  - The O-antigen of the lipopolysaccharide from Escherichia coli O166 has been
      determined by component analysis together with 1D and 2D NMR spectroscopy
      techniques. The polysaccharide has pentasaccharide repeating units consisting of
      D-glucose (1), D-galactose (2) and N-acetyl-D-galactosamine (2) with the
      following structure: [ STRUCTURE: SEE TEXT]. In the 1H NMR, spectrum resonances
      of low intensity were observed. Further analysis of these showed that they
      originate from the terminal part of the polysaccharide, thereby revealing that
      the repeating unit has a 3-substituted N-acetyl-D-galactosamine residue at its
      reducing end.

PMID- 17182013
TI  - Methylmercury induces oxidative injury, alterations in permeability and glutamine
      transport in cultured astrocytes.
AB  - The neurotoxicity of high levels of methylmercury (MeHg) is well established both
      in humans and experimental animals. Astrocytes accumulate MeHg and play a
      prominent role in mediating MeHg toxicity in the central nervous system (CNS).
      Although the precise mechanisms of MeHg neurotoxicity are ill-defined, oxidative
      stress and altered mitochondrial and cell membrane permeability appear to be
      critical factors in its pathogenesis. The present study examined the effects of
      MeHg treatment on oxidative injury, mitochondrial inner membrane potential,
      glutamine uptake and expression of glutamine transporters in primary astrocyte
      cultures. MeHg caused a significant increase in F(2)-isoprostanes (F(2)-IsoPs),
      lipid peroxidation biomarkers of oxidative damage, in astrocyte cultures treated
      with 5 or 10 microM MeHg for 1 or 6 h. Consistent with this observation, MeHg
      induced a concentration-dependant reduction in the inner mitochondrial membrane
      potential (DeltaPsi(m)), as assessed by the potentiometric dye,
      tetramethylrhodamine ethyl ester (TMRE). Our results demonstrate that DeltaPsi(m)
      is a very sensitive endpoint for MeHg toxicity, since significant reductions were
      observed after only 1 h exposure to concentrations of MeHg as low as 1 microM.
      MeHg pretreatment (1, 5 and 10 microM) for 30 min also inhibited the net uptake
      of glutamine ((3)H-glutamine) measured at 1 min and 5 min. Expression of the mRNA
      coding the glutamine transporters, SNAT3/SN1 and ASCT2, was inhibited only at the
      highest (10 microM) MeHg concentration, suggesting that the reduction in
      glutamine uptake observed after 30 min treatment with lower concentrations of
      MeHg (1 and 5 microM) was not due to inhibition of transcription. Taken together,
      these studies demonstrate that MeHg exposure is associated with increased
      mitochondrial membrane permeability, alterations in glutamine/glutamate cycling,
      increased ROS formation and consequent oxidative injury. Ultimately, MeHg
      initiates multiple additive or synergistic disruptive mechanisms that lead to
      cellular dysfunction and cell death.

PMID- 17182017
TI  - Alkenyl and alkenoyl amphiphilic derivatives of D-xylose and their surfactant
      properties.
AB  - Unsaturated fatty alkyl xylosides and the corresponding 1-O-acyl esters were
      prepared. Critical micellar concentrations, surface tension areas per molecule
      and foaming value of some of these new amphiphilic compounds have been
      determined.

PMID- 17182016
TI  - Structure of the O-polysaccharide and serological cross-reactivity of the
      lipopolysaccharide of Providencia alcalifaciens O32 containing N-acetylisomuramic
      acid.
AB  - The O-polysaccharide was obtained by mild acid degradation of the
      lipopolysaccharide of Providencia alcalifaciens O32 and studied by sugar and
      methylation analyses, solvolysis with triflic acid, 1H and 13C NMR spectroscopy,
      including two-dimensional 1H,1H COSY, TOCSY, ROESY, H-detected 1H,13C HSQC and
      HMBC experiments. It was found that the polysaccharide has a branched
      tetrasaccharide repeating unit containing 2-acetamido-3-O-[(S)-1-carboxyethyl]-2
      deoxy-D-glucose (D-GlcNAc3Slac, N-acetylisomuramic acid) with the following
      structure: [ STRUCTURE: SEE TEXT]. Serological studies with O-antisera showed
      antigenic relationships between P. alcalifaciens O32 and O29 as well as several
      other Providencia and Proteus strains sharing putative epitopes on the O
      polysaccharides.

PMID- 17182018
TI  - A new glycosidation method through nitrite displacement on substituted
      nitrobenzenes.
AB  - Benzyl, benzoyl, and acetyl protected 1-OH and 1-SH glycoses in the glucose,
      glucosamine, galactose, mannose, and lactose series react with nitrobenzenes
      activated by one or two electron withdrawing substituents like nitro and cyano to
      afford the corresponding aryl glycosides in 50-100% yield. The S(N)Ar
      displacement of nitrite by 1-OH glycoses is reversible and gives predominantly
      the alpha-glycosides, whereas 1-SH glycoses do not anomerize and afford the beta
      glycosides. Thus, the prepared dicyanophenyl gycosides are useful building blocks
      for the preparation of phthalocyanine-glycoconjugates via template synthesis.

PMID- 17182019
TI  - Synthesis of an experimental glycolipoprotein vaccine against Lyme disease.
AB  - A novel glycolipid was synthesized that corresponds to cholesteryl palmitoyl
      galactopyranoside 1 found in the spirochete Borrelia burgdorferi, the causative
      agent of Lyme disease. In order to fashion 1 in a conjugatable form, the
      palmitoyl residue was modified to include a terminal aldehydo moiety that
      anchored the glycolipid to aminooxypropylated serum albumin using oxime
      chemistry. The glycolipoprotein so obtained incorporates an average of 18
      glycolipid moieties per albumin molecule. The novel glycolipoprotein constructs
      are soluble in water and are candidates toward developing a semisynthetic vaccine
      against Lyme disease.

PMID- 17182021
TI  - A medical health report on individuals with silent butyrylcholinesterase in the
      Vysya community of India.
AB  - BACKGROUND: Butyrylcholinesterase (BChE; gi:116353) deficiency has adverse
      effects on the response to succinylcholine and mivacurium. A physiological
      function of BChE is to inactivate octanoyl ghrelin. We determined the health
      effect of complete absence of BChE in humans. METHODS: Clinical tests of cardiac,
      lung, liver, and kidney function, body weight, sperm counts and motility were
      performed on 5 men, age 20-32 y, in the Vysya community of Coimbatore, India who
      had silent BChE. Postmortem tissues from 2 cadavers with wild-type BChE were
      assayed. RESULTS: Test results were normal, except for lung function, which
      indicated mild obstruction in silent as well as in wild-type BChE subjects.
      Creatine kinase-MB levels were high in 2 subjects, but there were no other
      indications of damage to the heart. Body weight was normal. Family histories
      revealed no trend in disease susceptibility. The human body contains 10 times
      more BChE than acetylcholinesterase molecules. CONCLUSION: Individuals completely
      deficient in BChE have only minor abnormalities in clinical test results.
      However, they respond abnormally to standard doses of succinylcholine and
      mivacurium. It is expected, but not proven, that they are unusually susceptible
      to the toxicity of cocaine and organophosphorus pesticides, and resistant to
      bambuterol and irinotecan. Their normal body weight suggests alternative routes
      for deactivation of octanoyl ghrelin.

PMID- 17182020
TI  - Diabetes mellitus attenuates the repolarization reserve in mammalian heart.
AB  - OBJECTIVE: In diabetes mellitus several cardiac electrophysiological parameters
      are known to be affected. In rodent experimental diabetes models changes in these
      parameters were reported, but no such data are available in other mammalian
      species including the dog. The present study was designed to analyse the effects
      of experimental type 1 diabetes on ventricular repolarization and its underlying
      transmembrane ionic currents and channel proteins in canine hearts. METHODS AND
      RESULTS: Diabetes was induced by a single injection of alloxan, a subgroup of
      dogs received insulin substitution. After the development of diabetes (8 weeks)
      electrophysiological studies were performed using conventional microelectrodes,
      whole cell voltage clamp, and ECG. Expression of ion channel proteins was
      evaluated by Western blotting. The QTc interval and the ventricular action
      potential duration in diabetic dogs were moderately prolonged. This was
      accompanied by significant reduction in the density of the transient outward K+
      current (I(to)) and the slow delayed rectifier K+ current (I(Ks)), to 54.6% and
      69.3% of control, respectively. No differences were observed in the density of
      the inward rectifier K+ current (I(K1)), rapid delayed rectifier K+ current
      (I(Kr)), and L-type Ca2+ current (I(Ca)). Western blot analysis revealed a
      reduced expression of Kv4.3 and MinK (to 25+/-21% and 48+/-15% of control,
      respectively) in diabetic dogs, while other channel proteins were unchanged
      (HERG, MiRP1, alpha(1c)) or increased (Kv1.4, KChIP2, KvLQT1). Insulin
      substitution fully prevented the diabetes-induced changes in I(Ks), KvLQT1 and
      MinK, however, the changes in I(to), Kv4.3, and Kv1.4 were only partially
      diminished by insulin. CONCLUSION: It is concluded that type 1 diabetes mellitus,
      although only moderately, lengthens ventricular repolarization, attenuates the
      repolarization reserve by decreasing I(to) and I(Ks) currents, and thereby may
      markedly enhance the risk of sudden cardiac death.

PMID- 17182022
TI  - NT-proBNP correlates not only with ejection fraction, but also with inferior vena
      cava diameter in patients with acute heart failure.

PMID- 17182023
TI  - Do 12.5-month-old infants consider what objects others can see when interpreting
      their actions?
AB  - The present research examined whether 12.5-month-old infants take into account
      what objects an agent knows to be present in a scene when interpreting the
      agent's actions. In two experiments, the infants watched a female human agent
      repeatedly reach for and grasp object-A as opposed to object-B on an apparatus
      floor. Object-B was either (1) visible to the agent through a transparent screen;
      (2) hidden from the agent (but not the infants) by an opaque screen; or (3)
      placed by the agent herself behind the opaque screen, so that even though she
      could no longer see object-B, she knew of its presence there. The infants
      interpreted the agent's repeated actions toward object-A as revealing a
      preference for object-A over object-B only when she could see object-B (1) or was
      aware of its presence in the scene (3). These results indicate that, when
      watching an agent act on objects in a scene, 12.5-month-old infants keep track of
      the agent's representation of the physical setting in which these actions occur.
      If the agent's representation is incomplete, because the agent is ignorant about
      some aspect of the setting, infants use the agent's representation, rather than
      their own more complete representation, to interpret the agent's actions.

PMID- 17182024
TI  - Reduced model and simulation of myelinated axon using eigenfunction expansion and
      singular perturbation.
AB  - In a myelinated axon, there exist many nodes of Ranvier where myelin sheaths are
      absent and action potentials are actively regenerated. Hence, a myelinated axon
      is a nonuniform cable where myelinated parts and unmyelinated nodes of Ranvier
      are described by different cable equations. For the modelling of a myelinated
      axon, the compartment model based on finite volume or finite difference
      discretization was dominantly used. In this paper, we propose a hybrid approach
      where an eigenfunction expansion combined with singular perturbation is employed
      for myelinated parts, and demonstrate that the proposed scheme can achieve an
      order of magnitude accuracy improvement for low order models. Moreover, it is
      also shown that the proposed scheme converges faster to attain a given accuracy.
      Hence, for simulation of myelinated axons, the proposed scheme can be an
      attractive alternative to the compartment model, that leads to a low order model
      with much higher accuracy or that converges faster for a given accuracy.

PMID- 17182025
TI  - Pharmacodynamic monitoring of the immunosuppressive therapy in patients after
      heart transplantation: whole blood flow cytometric analysis of lymphocyte
      function.
AB  - Despite therapeutic monitoring and daily measurements of blood concentrations
      (pharmacokinetics) of immunosuppressive medications, immunosuppressive therapy
      remains still a challenge after heart transplantation (HTx) due to drug
      interactions, toxicities and individual responses to drug effects. We established
      whole blood flow cytometric assays of lymphocyte function to assess the
      pharmacodynamics of immunosuppressive therapy and investigated both
      pharmacokinetic and pharmacodynamic approaches after HTx. Our results showed that
      pharmacodynamic measurements provide a more direct assessment of the functional
      activity of immunosuppressants on immune cells compared to drug level monitoring
      alone. The information from both pharmacokinetic and pharmacodynamic monitoring
      has the potential to increase the efficacy and safety of individual
      immunosuppressive therapy after HTx.

PMID- 17182026
TI  - Interactive volume cutting of medical data.
AB  - Volume data cutting plays a crucial part in medical image probing, computer
      assisted diagnosis, virtual surgery, etc. Based on hardware-accelerated texture
      based volume rendering algorithm, the paper proposes a method for volume cutting.
      With Boolean operations, the method is extended to multi-object clipping and can
      meet the needs of more complicated clipping applications. Due to hardware
      acceleration, proposed algorithms achieve interactive display rate and can be
      used in volume cutting applications such as surgery simulation and so on.

PMID- 17182027
TI  - Lung nodule diagnosis using 3D template matching.
AB  - In this paper, to utilize the third dimension of Computed Tomography, regions of
      interest (ROI) slices were combined to form 3D ROI image and a 3D template was
      determined to find the structures with similar properties of nodules. Convolution
      of 3D ROI image with the proposed template strengthens the shapes similar to the
      template and weakens the other ones. False-positive (FP) per nodule and per slice
      versus diagnosis sensitivity were obtained. The Computer Aided Diagnosis system
      achieved 100% sensitivity with 0.83 FP per nodule and 0.46 FP per slice, when the
      nodule thickness was greater than or equal to 5.625 mm.

PMID- 17182028
TI  - The last 59 amino acids of Smoothened cytoplasmic tail directly bind the protein
      kinase Fused and negatively regulate the Hedgehog pathway.
AB  - The Hedgehog (HH) signaling pathway is crucial for the development of many
      organisms and its inappropriate activation is involved in numerous cancers. HH
      signal controls the traffic and activity of the seven-pass transmembrane protein
      Smoothened (SMO), leading to the transcriptional regulation of HH-responsive
      genes. In Drosophila, the intracellular transduction events following SMO
      activation depend on cytoplasmic multimeric complexes that include the Fused (FU)
      protein kinase. Here we show that the regulatory domain of FU physically
      interacts with the last 52 amino acids of SMO and that the two proteins
      colocalize in vivo to vesicles. The deletion of this region of SMO leads to a
      constitutive activation of SMO, promoting the ectopic transcription of HH target
      genes. This activation is partially dependent of FU activity. Thus, we identify a
      novel link between SMO and the cytoplasmic complex(es) and reveal a negative role
      of the SMO C-terminal region that interacts with FU. We propose that FU could act
      as a switch, activator in presence of HH signal or inhibitor in absence of HH.

PMID- 17182029
TI  - Effects of the treatment with glibenclamide, an ATP-sensitive potassium channel
      blocker, on intestinal ischemia and reperfusion injury.
AB  - Intestinal ischemia and reperfusion injury is dependent on the recruitment and
      activation of neutrophils. Glibenclamide, an ATP-sensitive potassium channel
      (K(ATP)) blocker, has been shown to suppress neutrophil migration and chemotaxis
      during acute inflammatory responses by a mechanism dependent on its K(ATP)
      channel blocking activity. In the present study, we evaluated whether the
      treatment with glibenclamide prevented local, remote and systemic injury
      following reperfusion of the ischemic superior mesenteric artery in rats. The
      artery was made ischemic for a period of 30 or 120 min followed by 30 (mild I/R)
      or 120 (severe I/R) min of reperfusion, respectively. Glibenclamide (0.8 to 20
      mg/kg) or vehicle was administered subcutaneously 40 min prior to the
      reperfusion. Glibenclamide dose-dependently inhibited the reperfusion-associated
      increase in vascular permeability and neutrophil accumulation in mild I/R. In the
      severe injury model, glibenclamide inhibited inflammatory parameters, as assessed
      by Evans blue extravasation, neutrophil influx and haemoglobin content, and the
      increase in TNF-alpha (tumor necrose factor-alpha) and IL (interleukin)-6 levels
      in the intestine and lung. The drug did not affect the increase in IL-1beta and
      IL-10 levels. TEA, a nonselective potassium channel blocker, also inhibited
      reperfusion injury in both intestine and lungs of animals submitted to mild and
      severe I/R. Our experiments suggest a role for K(ATP) channels in mediating
      neutrophil influx and consequent reperfusion-associated injury in rats. The lack
      of effect of these drugs on the reperfusion-associated hypotension and lethality
      may limit their usefulness after severe reperfusion injury.

PMID- 17182030
TI  - Inhibition of HtrA2/Omi ameliorates heart dysfunction following
      ischemia/reperfusion injury in rat heart in vivo.
AB  - High temperature requirement A2 (HtrA2)/Omi is a mitochondrial serine protease
      that is released into the cytosol from mitochondria and in turn promotes caspase
      activation by proteolyzing inhibitor of apoptosis proteins. Here we asked whether
      treatment with an HtrA2/Omi inhibitor, 5-[5-(2-nitrophenyl)furfuryliodine]-1,3
      diphenyl-2-thiobarbituric acid (UCF-101), restores heart dysfunction following
      ischemia/reperfusion injury in vivo. Rats underwent a 30-min ischemia by
      occluding the left anterior descending artery, followed by 24 h reperfusion. UCF
      101 (0.75 or 1.5 micromol/kg, i.p.) was administered 10 min before reperfusion.
      UCF-101 treatment significantly recovered the mean arterial blood pressure and
      ameliorated contractile dysfunction of the left ventricle 72 h after reperfusion
      with concomitant reduction of infarct size. Cardio-protection mediated by UCF-101
      was correlated with reduced X-linked inhibitor of apoptosis protein (XIAP)
      degradation and inhibition of Caspase-9, Caspase-3, and Caspase-7 processing.
      Furthermore, UCF-101 prevented loss of membrane integrity by inhibiting fodrin
      breakdown in cardiomyocytes. UCF-101-induced cytoprotection was also correlated
      with reduced Fas ligand expression and inhibition of FLIP degradation following
      ischemia/reperfusion. These results suggest that UCF-101 rescues cardiomyocytes
      from ischemia/reperfusion injury by inhibiting XIAP degradation and Fas/Fas
      ligand-induced apoptosis, thereby ameliorating ischemia/reperfusion-induced
      myocardial dysfunction.

PMID- 17182031
TI  - Role of the peripheral heme oxygenase-carbon monoxide pathway on the nociceptive
      response of rats to the formalin test: evidence for a cGMP signaling pathway.
AB  - The aim of the present study was to investigate the role of the peripheral heme
      oxygenase (HO)-carbon monoxide (CO) pathway on nociceptive response of rats to
      the formalin experimental model of pain. Animals were handled and adapted to the
      experimental environment for a few days before the formalin test was applied. For
      the formalin test, 50 microl of a 1% formalin solution was used and injected
      subcutaneously in the dorsal surface of the right hind paw. Following injections,
      animals were observed for 1 h, and flinching behavior was measured as the
      nociceptive response. Twenty minutes before the test rats were pretreated with
      podal injections with the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol
      (ZnDPBG) or heme-lysinate, which is known to induce the HO pathway. Control
      animals were treated with vehicles. We observed a significant increase on
      nociceptive response of rats treated with ZnDPBG, and a drastic reduction of
      flinching nociceptive behavioral response in the heme-lysinate and CO treated
      animals. Among the three different HO products, CO seems to account for the heme
      lysinate effect because the injection of the gas attenuated the flinching
      response whereas biliverdine and deferoxanine (an iron chelator) failed to cause
      any significant change. Furthermore, CO seems to act via cGMP, since methylene
      blue (a soluble guanylate cyclase inhibitor) prevented the reduction of the
      flinching nociceptive behavioral response caused by heme-lysinate. These findings
      strongly indicate that CO is the HO pathway product that plays an antinociceptive
      role during the formalin test, acting via cGMP.

PMID- 17182032
TI  - Impaired vascular function in normoglycemic mice prone to autoimmune diabetes:
      role of nitric oxide.
AB  - Type 1 diabetes is an immuno-inflammatory condition which increases the risk of
      cardiovascular disease, particularly in young adults. This study investigated
      whether vascular function is altered in mice prone to autoimmune diabetes and
      whether the nitric oxide (NO)-cyclic GMP axis is involved. Aortic rings suspended
      in organ chambers and precontracted with phenylephrine were exposed to cumulative
      concentrations of acetylcholine. To investigate the role of NO, some experiments
      were performed in the presence of either 1400W (N-(3-aminomethyl)benzyl
      acetamidine hydrochloride), a selective inhibitor of the iNOS-isoform, L-NAME
      (N(G)-nitro-L-arginine methyl ester hydrochloride), an inhibitor of all three NOS
      isoforms, or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), a selective
      inhibitor of guanylate cyclase. Moreover, contractility to phenylephrine, big
      endothelin-1, and endothelin-1 was assessed and histological analysis and iNOS
      immunohistochemistry were performed. Endothelium-dependent relaxation was reduced
      in prediabetic NOD mice (78+/-4 vs. 88+/-2%, respectively, P<0.05 vs. control)
      despite normal plasma glucose levels (n.s. vs. control). Preincubation with 1400W
      further attenuated responses in prediabetic (P<0.05 vs. untreated) but not in
      diabetic or in control mice. In contrast, basal NO bioactivity remained
      unaffected until the onset of diabetes in NOD mice. Contractile responses to big
      endothelin-1 and endothelin-1 were reduced in prediabetic animals (P<0.05 vs.
      control), whereas in diabetic mice only responses to big endothelin-1 were
      decreased (P<0.05 vs. control). These data demonstrate that endothelium-dependent
      and -independent vascular function in NOD mice is abnormal already in prediabetes
      in the absence of structural injury. Early proinflammatory activation due to iNOS
      in diabetes-prone NOD mice appears to be one of the mechanisms contributing to
      impaired vasoreactivity.

PMID- 17182033
TI  - Flt3 ligand generates morphologically distinct semimature dendritic cells in
      ovalbumin-sensitized mice.
AB  - Dendritic cells (DCs) are unique antigen presenting cells that are immature prior
      to their encounter with an antigen. Exposure to allergens induces the maturation
      of DCs with changes in morphology and presence of dendrites. Here, we demonstrate
      that the DCs in the lungs of ovalbumin (OVA)-sensitized and challenged mice are
      more mature owing to their pronounced dendrites than the DCs in the lungs and
      spleen of PBS-treated mice, which are immature and possess cytoplasmic veils.
      Intermediate to these two groups are the DCs in the Flt3 ligand-treated group
      that exhibit comparatively fewer dendrites and cytoplasmic veils and hence are
      classified as semimature. Presence of large numbers of well-developed
      mitochondria and rough endoplasmic reticulum in myeloid DCs from both lungs and
      spleen of OVA-sensitized and challenged mice indicate greater functional
      activity. Additionally, DCs from the OVA-sensitized and challenged mice also
      exhibit fat and glycogen stores, which are indicative of a mature population. In
      addition, treatment of the animals with Flt3 ligand attenuated airway
      hyperresponsiveness to methacholine in OVA-sensitized and challenged mice. These
      data suggest that morphological features could be indicative of the maturation
      and distinct functional state of DCs, and this could be associated with
      underlying mechanisms of Flt3 ligand-induced immunomodulation in allergic asthma.

PMID- 17182035
TI  - RhoE interferes with Rb inactivation and regulates the proliferation and survival
      of the U87 human glioblastoma cell line.
AB  - Rho GTPases are important regulators of actin cytoskeleton, but they are also
      involved in cell proliferation, transformation and oncogenesis. One of this
      proteins, RhoE, inhibits cell proliferation, however the mechanism that regulates
      this effect remains poorly understood. Therefore, we undertook the present study
      to determine the role of RhoE in the regulation of cell proliferation. For this
      purpose we generated an adenovirus system to overexpress RhoE in U87 glioblastoma
      cells. Our results show that RhoE disrupts actin cytoskeleton organization and
      inhibits U87 glioblastoma cell proliferation. Importantly, RhoE expressing cells
      show a reduction in Rb phosphorylation and in cyclin D1 expression. Furthermore,
      RhoE inhibits ERK activation following serum stimulation of quiescent cells.
      Based in these findings, we propose that RhoE inhibits ERK activation, thereby
      decreasing cyclin D1 expression and leading to a reduction in Rb inactivation,
      and that this mechanism is involved in the RhoE-induced cell growth inhibition.
      Moreover, we also demonstrate that RhoE induces apoptosis in U87 cells and also
      in colon carcinoma and melanoma cells. These results indicate that RhoE plays an
      important role in the regulation of cell proliferation and survival, and suggest
      that this protein may be considered as an oncosupressor since it is capable to
      induce apoptosis in several tumor cell lines.

PMID- 17182034
TI  - Topoisomerase II binds importin alpha isoforms and exportin/CRM1 but does not
      shuttle between the nucleus and cytoplasm in proliferating cells.
AB  - Resistance to anticancer drugs that target DNA topoisomerase II (topo II)
      isoforms alpha and/or beta is associated with decreased nuclear and increased
      cytoplasmic topo IIalpha. Earlier studies have confirmed that functional nuclear
      localization and export signal sequences (NLS and NES) are present in both
      isoforms. In this study, we show that topo II alpha and beta bind and are
      imported into the nucleus by importin alpha1, alpha3, and alpha5 in conjunction
      with importin beta. Topo IIalpha also binds exportin/CRM1 in vitro. However, wild
      type topo IIalpha has only been observed in the cytoplasm of cells that are
      entering plateau phase growth. This suggests that topo IIalpha may shuttle
      between the nucleus and the cytoplasm with the equilibrium towards the nucleus in
      proliferating cells but towards the cytoplasm in plateau phase cells. The CRM1
      inhibitor Leptomycin B increases the nuclear localization of GFP-tagged topo
      IIalpha with a mutant NLS, suggesting that its export is being inhibited.
      However, homokaryon shuttling experiments indicate that fluorescence-tagged wild
      type topo II alpha and beta proteins do not shuttle in proliferating Cos-1 or
      HeLa cells. We conclude that topo II alpha and beta nuclear export is inhibited
      in proliferating cells so that these proteins do not shuttle.

PMID- 17182037
TI  - Identification of proteins whose expression is up- or down-regulated in the
      mushroom bodies in the honeybee brain using proteomics.
AB  - To identify protein(s) with different expression patterns in the mushroom bodies
      (MBs) in the honeybee brain, we compared the protein profiles of MBs and optic
      lobes (OLs) using proteomics. Two-dimensional gel electrophoresis revealed that
      five and three spots were selectively expressed in the MBs or OLs, respectively.
      Liquid chromatography tandem mass spectrometry analysis identified juvenile
      hormone diol kinase and glyceraldehyde-3-phosphate dehydrogenase as MB- and OL
      selective proteins, respectively. In situ hybridization revealed that jhdk
      expression was upregulated in MB neuron subsets, whereas gapdh expression was
      downregulated, indicating that MBs have a distinct gene and protein expression
      profile in the honeybee brain.

PMID- 17182036
TI  - Studies on the protective immunity of Schistosoma japonicum bivalent DNA vaccine
      encoding Sj23 and Sj14.
AB  - In order to explore the high performance bivalent DNA vaccine of Schistosoma
      japonicum, the fatty-acid-binding protein (Sj14) and the 23 kDa transmembrane
      protein (Sj23) two proteins were selected to construct the DNA-based vaccine. It
      was successful to construct a bivalent DNA vaccine using three strategies: the co
      expression of two genes, a fusion gene expression and two kinds of plasmids in
      combination (cocktail vaccine). The bivalent DNA was proven to express well in
      vitro and in vivo by indirect immunofluorescence test (IIF) and reverse
      transcriptase-polymerase chain reaction (RT-PCR). The protective immunity of
      bivalent DNA vaccine was higher than that of univalent DNA vaccine (p<0.05).
      There were four groups of bivalent vaccine whose protective immunity was higher
      than 50%. Granuloma diameter reduction rates were in the range of 18-39%. There
      was no significant impact on immunity protection exerted by the four factors
      including dosage, inoculated times, inoculated routes and challenge time after
      the last immunization in three levels (p>0.05).

PMID- 17182038
TI  - Peg1/Mest in obese adipose tissue is expressed from the paternal allele in an
      isoform-specific manner.
AB  - Paternally expressed 1 (Peg1)/mesoderm specific transcript (Mest) is an imprinted
      gene, which is only transcribed from the paternal (father's) allele. In some
      human cancer tissues, an alternatively spliced variant of PEG1/MEST mRNA using a
      different promoter of a distinct first exon is expressed from both paternal and
      maternal alleles. We previously reported that Peg1/Mest expression was markedly
      up-regulated in obese adipose tissue in mice. Moreover, transgenic overexpression
      of Peg1/Mest in the adipose tissue resulted in the enlargement of adipocytes in
      size. Given the potential pathophysiologic relevance in obesity, we examined the
      nature of increased expression of Peg1/Mest in obese adipose tissue. In obese
      adipose tissue, expression of Peg1/Mest was increased, but not that of other
      imprinted genes tested. The transcription rate of Peg1/Mest was increased in
      obese adipose tissue. We found at least four isoforms of mouse Peg1/Mest
      generated by use of the alternative first exons. We also demonstrated that the
      abundantly expressed Peg1/Mest in obese adipose tissue retained monoallelic
      expression. This is the first report of monoallelic induction of Peg1/Mest in
      adult tissues.

PMID- 17182039
TI  - A loop of coagulation factor VIIa influencing macromolecular substrate
      specificity.
AB  - Coagulation factor VIIa (FVIIa) belongs to a family of proteases being part of
      the stepwise, self-amplifying blood coagulation cascade. To investigate the
      impact of the mutation Met(298{156})Lys in FVIIa, we replaced the Gly(283{140})
      Met(298{156}) loop with the corresponding loop of factor Xa. The resulting
      variant exhibited increased intrinsic activity, concurrent with maturation of the
      active site, a less accessible N-terminus, and, interestingly, an altered
      macromolecular substrate specificity reflected in an increased ability to cleave
      factor IX (FIX) and a decreased rate of FX activation compared to that of wild
      type FVIIa. In complex with tissue factor, activation of FIX, but not of FX,
      returned to normal. Deconvolution of the loop graft in order to identify
      important side chain substitutions resulted in the mutant
      Val(158{21})Asp/Leu(287{144})Thr/Ala(294{152})Ser/Glu(296{154})
      Ile/Met(298{156})Lys-FVIIa with almost the same activity and specificity profile.
      We conclude that a lysine residue in position 298{156} of FVIIa requires a
      hydrophilic environment to be fully accommodated. This position appears critical
      for substrate specificity among the proteases of the blood coagulation cascade
      due to its prominent position in the macromolecular exosite and possibly via its
      interaction with the corresponding position in the substrate (i.e. FIX or FX).

PMID- 17182040
TI  - Sinusoidal swinging dynamics of the telomere repair and cell growth activation
      functions of telomerase in rat liver cancer cells.
AB  - Telomerase is a multimolecular complex of reverse transcriptase, RNA template,
      and regulatory proteins. It has two known functions: catalysis of the addition of
      [TTAGGG] repeats to telomeric DNA and the activation of various genes controlling
      cell proliferation. The possible coordination of these two functions is a key
      issue in understanding the growth of cancer cells. We report long-term changes to
      this complex system, as shown by specific data analysis methods. We show that the
      dynamics of the two functions of telomerase are tightly linked, with a change in
      predominant function every 13-14 weeks. The conservative behavior of this dynamic
      system probably accounts for the persistent proliferation of cancer cells.

PMID- 17182041
TI  - Involvement of a Rho-ROCK-JNK pathway in arsenic trioxide-induced apoptosis in
      chronic myelogenous leukemia cells.
AB  - The apoptotic signals activated by As(2)O(3) in the chronic myelogenous leukemia
      (CML) cell lines K562 and KCL22 were investigated. As(2)O(3) was found to induce
      apoptosis in these cells via the intrinsic pathway. As(2)O(3) also induced a
      sustained c-Jun NH2-terminal kinase (JNK) activation which preceded and was
      necessary for caspase-9 activation. We established that Rho and its effector, the
      kinase ROCK, are activated by As(2)O(3). Inhibition of either Rho or ROCK
      prevented JNK activation and protected against apoptosis. Thus, in CML cells,
      apoptosis induced by As(2)O(3) is mediated, at least in part, via a Rho-ROCK-JNK
      axis. These findings define a novel signaling pathway for As(2)O(3)-induced
      apoptosis.

PMID- 17182042
TI  - Heat shock protein 70 inhibits the nuclear import of apoptosis-inducing factor to
      avoid DNA fragmentation in TF-1 cells during erythropoiesis.
AB  - Loss of mitochondrial membrane potential (DeltaPsi(m)) and release of AIF
      (apoptosis-inducing factor) from mitochondria are key steps in apoptosis. In TF-1
      model, DeltaPsi(m) was depolarized with AIF release during erythroid development.
      Yet, no DNA fragmentation was observed. When DeltaPsi(m) depolarization had been
      blocked, erythropoiesis was suppressed. Interestingly, heat shock protein 70
      (Hsp70) was found transiently upregulated during depolarization and it retained
      AIF in the cytosol to avoid DNA damages. When Hsp inhibitor was added, DNA
      fragmentation occurred. We show this mechanism for the first time in
      erythropoiesis how cells with DeltaPsi(m) depolarization and AIF release escape
      apoptosis.

PMID- 17182043
TI  - Intervertebral disc recovery after dynamic or static loading in vitro: is there a
      role for the endplate?
AB  - In vivo studies on disc mechanics show loss of fluid from the intervertebral disc
      (IVD) during loading and full recovery during rest. Previous work indicated that
      in vitro recovery is hampered after static loading. The aim of the present study
      was to investigate the role of the endplate after dynamic and static loading on
      mechanical recovery in vitro. Lumbar spines (caprine) were obtained from the
      local slaughterhouse and stored frozen. Twenty-four intervertebral discs were
      thawed and subjected to a compression test in a saline bath (37 degrees C). The
      discs were pre-loaded at 20 N for 15 min. Three 15-min loading cycles (static:
      2.0 MPa or dynamic: average load 2.0 MPa at 0.5 Hz) were applied, each followed
      by a 30-min period of unloading (20 N). After this protocol, the endplates of
      half of the discs were blocked with silicone paste and the long-term recovery
      protocol was applied; the discs were subjected to a single loading cycle (15 min
      of static or dynamic loading) followed by 10h of unloading at 20 N. All specimens
      showed a net loss of height and a gain in stiffness during the first part of the
      test. Eventually, height and stiffness were restored during a long-term recovery
      test. The difference in recovery between blocked and free endplates was marginal.
      If fluid flow plays a role during recovery in vitro, the role of the endplate
      appears to be limited. Our findings show no influence of loading type on recovery
      in vitro.

PMID- 17182046
TI  - Development of a simple hollow fibre supported liquid membrane extraction method
      to extract and preconcentrate dinitrophenols in environmental samples at ng L(-1)
      level by liquid chromatography.
AB  - An easy and rapid hollow-fibre supported liquid membrane method (HFSLM) has been
      developed to extract and determinate the total concentration of four
      dinitrophenols in environmental water at ng L(-1) level. This extraction method
      provides a high selectivity, short extraction time and very low cost for real
      samples. It is a three-phase system, aqueous-organic-aqueous, where the organic
      solvent is held into the fibre pores, being in contact with the two other phases.
      The organic phase is formed by two different organic solvents, with two different
      polarities, n-undecane and toluene (1:1). The optimization step was performed
      using a three-variable Doehler design, involving three factors, stirring speed,
      fibre length and sample volume. The organic phase composition, as well as the pH
      of the acceptor and donor phases was also optimized. The extraction equilibrium
      was reached after 30 min, after which essentially the total amount (90-80%) of
      the four dinitrophenolic compounds were extracted from the sample. Better
      repeatability and reproducibility at the expense of lower enrichment factors was
      obtained compared with other methods, employing incomplete extraction during a
      fixed time. The matrix effect was tested by performing extractions from leachate
      water and river water. This method is linear in the range 0.1-100 microgL(-1) in
      different matrices, with detection limit around 100 ng L(-1), after extraction of
      6 mL of sample and using high performance liquid chromatography for final
      analysis.

PMID- 17182044
TI  - Stability and repeatability of capillary columns based on porous monoliths of
      poly(butyl methacrylate-co-ethylene dimethacrylate).
AB  - Monolithic poly(butyl methacrylate-co-ethylene dimethacrylate) capillary columns
      have been prepared via either thermally or photochemically initiated
      polymerization of the corresponding monomers and the repeatability of their
      preparation has been explored. Three separate batches of 5 columns each were
      prepared using thermal and photochemical initiation for a total of 30 columns.
      All 30 capillary columns were tested in liquid chromatography-electrospray
      ionisation mass spectrometry mode for the separation of a model mixture of three
      proteins--ribonuclease A, cytochrome c and myoglobin. Excellent repeatability of
      retention times was observed for the proteins as evidenced by relative standard
      deviation (RSD) values of less than 1.5%. Somewhat broader variations with RSD
      values of up to 10% were observed for the pressure drop in the columns. The
      stability of retention times was also monitored using a single monolithic column
      and no significant shifts in either retention times or back pressure was observed
      in a series of almost 2200 consecutive protein separations.

PMID- 17182047
TI  - Continuous flow configuration for total hydrocarbons index determination in soils
      by evaporative light scattering detection.
AB  - A continuous flow configuration is proposed for the estimation of the hydrocarbon
      index in soils using for the first time evaporative light scattering detection
      (ELSD). The method is based on a membrane-enrichment of the hydrocarbons of
      interest (C10-C40), which are previously extracted from the soil matrix with a
      water:hexane mixture using a household microwave oven. The organic supernatant is
      cleaned-up through silica, evaporated and redissolved in a sodium dodecyl
      sulphate aqueous solution which is introduced in the loop of an injection valve.
      The sample, carried by an aqueous stream, passes through a continuous filtration
      unit fitted with a 1 microm pore size PTFE membrane, where the hydrocarbons are
      retained while the potential coextracted compounds are wasted. Quantitative
      elution of the C10-C40 fraction is accomplished by passing an acetone stream
      through the filter which drives the analytes to the ELSD system for analytical
      measurement. The detection limit was 1.8 microg ml(-1), the linear range 5-25
      microg ml(-1) and the precision 4.3%. The recoveries were between 93 and 97%. The
      proposed method was also evaluated by attenuated total reflexion-Fourier
      transform (ATR-FT-IR) analysis of the extracts.

PMID- 17182048
TI  - Homolog separation, a necessity for the proper identification of fungal
      metabolites.
AB  - Monitoring of fungal extracts for the production of novel metabolites, using a
      modular analytical system combining HPLC with UV-MS-ELS detection, identified
      culture LL-W1278 as a fungus producing new biopolymers. Only a non-routine HPLC
      analysis of a culture extract revealed that the standard water-acetonitrile
      elution method did not separate all members of the metabolite complex. Fine
      tuning the eluting solvents established that it was essential to include acid
      with the water-methanol system to separate the new materials. The routinely used
      water-acetonitrile system, with or without acid, was incapable of separating all
      homologues. With the modified method the new homologues W1278-Ax, Bx, and Cx were
      separated. LC/MS analysis indicated that these compounds had molecular weights of
      706, 900, and 1094, respectively, 44 mass units lower than their three major
      homologues, W1278-A, B, and C, identified previously. UV and NMR data as well as
      mass fragmentation patterns established unambiguously that the new compounds
      lacked a carboxyl group at the terminal resorcinol unit of the biopolymer,
      consisting of several catenated hydroxymellein residues. A time study concerning
      the stability of these fungal metabolites showed a slow, but complete degradation
      of the primary metabolites over several months when kept as a DMSO solution.

PMID- 17182049
TI  - Gas chromatography/mass spectrometry versus liquid chromatography/fluorescence
      detection in the analysis of phenols in mainstream cigarette smoke.
AB  - A new gas chromatographic/mass spectrometric (GC/MS) technique for the analysis
      of hydroxybenzenes (phenols) in mainstream cigarette smoke has been developed.
      The technique allows the measurement of 24 individual compounds, and the sum of a
      few other alkyl-dihydroxybenzenes. A critical evaluation is done for the new
      technique and for an established high-performance liquid chromatographic (HPLC)
      technique reported in the literature for the analysis of hydroxybenzenes in
      cigarette smoke, which uses fluorescence detection. Compared with the HPLC
      procedure, the new technique has similar accuracy, precision, and robustness.
      However, the GC/MS procedure allows for a larger number of phenols to be analyzed
      simultaneously, and eliminates any potential interference that may appear in the
      HPLC method. Using the GC/MS analysis, it was found that besides the main phenols
      typically measured in mainstream cigarette smoke such as phenol, catechol,
      hydroquinone, and cresols, many other phenols that are present at lower levels
      can be quantitated in mainstream cigarette smoke.

PMID- 17182050
TI  - Linear stability of a draining film squeezed between two approaching droplets.
AB  - In the present paper we analyze the effect of infinitesimal non-axisymmetric
      perturbations in determining the critical gap thickness at which a draining,
      finite radius thin-film becomes unstable. The film is part of the suspending
      fluid trapped between two approaching deformable drops under the action of a flow
      field. We carry out a linear stability analysis in the context of a quasi-static
      approximation where the rate of growth of the disturbances is assumed to be much
      faster than the rate of film drainage. An analytical solution is derived for the
      model in the special case of a uniformly thick film, for two types of
      perturbation: fixed-end and free-end. It is shown, for this special case, when
      the hydrodynamic force pushing the drops together from the external flow is
      constant, that the four most unstable disturbances are of the free-end kind,
      associated with the lowest frequency modes of azimuthal variation in the film
      thickness. Higher modes are stabilized by surface tension. Our analysis also
      shows that adopting the unretarded form of the van der Waals disjoining pressure
      yields results similar to the analysis when electromagnetic retardation effects
      are included in the calculation. A second case is analyzed where the film is also
      of uniform thickness but its lateral extent and the gap thickness are both time
      dependent. This case was included to extend the predictions to glancing drop
      collisions where the external hydrodynamic force is time-dependent. We find that
      there is a maximum capillary number below which the film becomes unstable, and
      that there is range of angles in the trajectory where the film becomes unstable,
      but that outside this range the film is stable.

PMID- 17182051
TI  - Chemical shift imaging of molecular transport in colloidal systems: visualization
      and quantification of diffusion processes.
AB  - Magnetic resonance imaging with chemical shift resolution is demonstrated to
      provide detailed information about molecular transport on the macroscopic scale
      in complex colloidal systems. The concentrations of species with distinct 1H
      resonance lines can be quantified from spatially resolved, high-resolution, 1H
      nuclear magnetic resonance spectra. The method is demonstrated by experiments on
      three systems with multiple simultaneous transport processes where the diffusion
      coefficients depend on position and/or on the concentration of other species: (1)
      release of poly(ethylene glycol) and imidazole from a hydrogel into an external
      reservoir of water, (2) migration of acetic acid and tetramethylammonium ions in
      a highly concentrated water-in-oil emulsion with initially non-uniform
      concentration of solutes, and (3) release of tetramethylammonium ions loaded into
      a hydrogel triggered by the diffusion of methyl green into the gel matrix.

PMID- 17182052
TI  - Synthesis and characterization of mesoporous ceria/alumina nanocomposite
      materials via mixing of the corresponding ceria and alumina gel precursors.
AB  - Mesoporous ceria/alumina, CeO(2)/Al(2)O(3), composites containing 10, 20 and 30%
      (w/w) ceria were prepared by a novel gel mixing method. In the method, ceria gel
      (formed via hydrolysis of ammonium cerium(IV) nitrate by aqueous ammonium
      carbonate solution) and alumina gel (formed via controlled hydrolysis of aluminum
      tri-isopropoxide) were mixed together. The mixed gel was subjected to subsequent
      drying and calcination for 3 h at 400, 600, 800 and 1000 degrees C. The
      uncalcined (dried at 110 degrees C) and the calcined composites were investigated
      by different techniques including TGA, DSC, FTIR, XRD, SEM and nitrogen
      adsorption/desorption isotherms. Results indicated that composites calcined for 3
      h at 800 degrees C mainly kept amorphous alumina structure and gamma-alumina
      formed only upon calcinations at 1000 degrees C. On the other hand, CeO(2) was
      found to crystallize in the common ceria, cerinite, phase and it kept this
      structure over the entire calcination range (400-1000 degrees C). Therefore, high
      surface areas, stable surface textures, and non-aggregated nano-sized ceria
      dispersions were obtained. A systematic texture change based on ceria ratio was
      observed, however in all cases mesoporous composite materials exposing thermally
      stable texture and structure were obtained. The presented method produces
      composite ceria/alumina materials that suit different applications in the field
      of catalysis and membranes technology, and throw some light on physicochemical
      factors that determine textural morphology and thermal stability of such
      important composite.

PMID- 17182053
TI  - Effect of particle size on surface modification of silica nanoparticles by using
      silane coupling agents and their dispersion stability in methylethylketone.
AB  - The effect of particle size on the reactivity of hexyltrimethoxysilane (C6S) with
      the particle surface was studied by using silica nanoparticles (SNPs) with
      different diameters (30 or 200 nm). In case of 30-nm SNPs, a large amount of
      isolated silanol was observed. On the other hand, in the case of 200-nm SNPs, the
      amount of hydrogen bonded silanol and hydrogen bonded water molecules at the
      surface of the SNPs increased. Since the hydrogen bonded silanol and the hydrogen
      bonded water enhanced the reaction of C6S with SNPs, the chemisorbed C6S on 200
      nm SNPs was larger than that on 30-nm SNPs. Furthermore, the effects of surface
      modification on the dispersion stability in MEK were studied using viscosity
      measurements and surface force measurements by the AFM colloid probe method. The
      viscosity of the dilute SNPs/MEK suspension did not change by the chemisorptions
      of C6S; however, the viscosity of dense suspension reduced effectively by surface
      modification. It was estimated that the suspension viscosity reduced effectively
      when the mean particle surface distance in the suspension was near to the
      distance where the repulsive force appeared by the surface force measurements
      using the colloid probe AFM.

PMID- 17182054
TI  - Aggregation behaviour of a dirhamnolipid biosurfactant secreted by Pseudomonas
      aeruginosa in aqueous media.
AB  - The process of micelle formation, along with the formation of higher order
      aggregates, is described for a dirhamnolipid extracellular biosurfactant secreted
      by Pseudomonas aeruginosa. As determined by surface tension measurements, at pH
      7.4 the CMC of dirhamnolipid is 0.110 mM, whereas at pH 4.0 it falls to 0.010 mM,
      indicating that the negatively charged diRL has a much higher CMC value than the
      neutral species. Centrifugation and dynamic light scattering measurements show
      formation of larger aggregates at concentrations above the CMC. These aggregates
      have been shown by electron microscopy to be mainly multilamellar vesicles of
      heterogeneous size. X-ray scattering gave a value of 32 A for the interlamellar
      repeat distance of these vesicles. Taking into account the experimental data, a
      molecular modelling of the dirhamnolipid moiety has been carried out, which
      details the size of the hydrophilic and hydrophobic portions, and suggests the
      possible intermolecular interactions responsible for the stabilisation of
      dirhamnolipid aggregates. The relevance of this aggregation behaviour is
      discussed with respect to the molecular basis of its activities.

PMID- 17182056
TI  - The 1.6 A crystal structure of the catalytic domain of PlyB, a bacteriophage
      lysin active against Bacillus anthracis.
AB  - Lysins are peptidoglycan hydrolases that are produced by bacteriophage and act to
      lyse the bacterial host cell wall during progeny phage release. Here, we describe
      the structure and function of a novel bacteriophage-derived lysin, PlyB, which
      displays potent lytic activity against the Bacillus anthracis-like strain ATCC
      4342. This molecule comprises an N-terminal catalytic domain (PlyB(cat)) and a C
      terminal bacterial SH3-like domain, SH3b. It is shown that both domains are
      required for effective catalytic activity against ATCC 4342. Further, PlyB has
      specific activity comparable to the phage lysin PlyG, an amidase being developed
      as a therapeutic against anthrax. In contrast to PlyG, however, the 1.6 A X-ray
      crystal structure of PlyB(cat) reveals that the catalytic domain adopts the
      glycosyl hydrolase (GH)-25, rather than phage T7 lysozyme-like fold. PlyB
      therefore represents a new class of anthrax lysin and a new defensive tool in the
      armament against anthrax-mediated bioterrorism.

PMID- 17182055
TI  - The X-ray crystal structures of two constitutively active mutants of the
      Escherichia coli PhoB receiver domain give insights into activation.
AB  - The PhoR/PhoB two-component system is a key regulatory protein network enabling
      Escherichia coli to respond to inorganic phosphate (Pi) starvation conditions by
      turning on Pho regulon genes for more efficient Pi uptake and use of alternative
      phosphorus sources. Under environmental Pi depletion, the response regulator (RR)
      component, PhoB, is phosphorylated at the receiver domain (RD), a process that
      requires Mg(2+) bound at the active site. Phosphorylation of the RD relieves the
      inhibition of the PhoB effector domain (ED), a DNA-binding region that binds to
      Pho regulon promoters to activate transcription. The molecular details of the
      activation are proposed to involve dimerization of the RD and a conformational
      change in the RD detected by the ED. The structure of the PhoB RD shows a
      symmetrical interaction involving alpha1, loop beta5alpha5 and N terminus of
      alpha5 elements, also seen in the complex of PhoB RD with Mg(2+), in which helix
      alpha4 highly increases its flexibility. PhoB RD in complex with Mg(2+) and
      BeF(3) (an emulator of the phosphate moiety) undergoes a dramatic conformational
      change on helix alpha4 and shows another interaction involving alpha4, beta5 and
      alpha5 segments. We have selected a series of constitutively active PhoB mutants
      (PhoB(CA)) that are able to turn on the Pho regulon promoters in the absence
      phosphorylation and, as they cannot be inactivated, should therefore mimic the
      active RD state of PhoB and its functional oligomerisation. We have analysed the
      PhoB(CA) RD crystal structures of two such mutants, Asp53Ala/Tyr102Cys and
      Asp10Ala/Asp53Glu. Interestingly, both mutants reproduce the homodimeric
      arrangement through the symmetric interface encountered in the unbound and
      magnesium-bound wild-type PhoB RD structures. Besides, the mutant RD structures
      show a modified active site organization as well as changes at helix alpha4 that
      correlate with repositioning of surrounding residues, like the active-site events
      indicator Trp54, putatively redifining the interaction with the ED in the full
      length protein.

PMID- 17182057
TI  - Depressive symptoms may explain elevated plasma levels of homocysteine in females
      with eating disorders.
AB  - Elevated plasma homocysteine levels have been found in different psychiatric
      disorders, including major depression and eating disorders. The aim of the
      present study was to evaluate whether presence of depression or depressive
      symptoms is associated with elevated homocysteine levels in patients with eating
      disorders. Total plasma homocysteine levels were assessed in 44 females with
      anorexia nervosa (n = 21) or bulimia nervosa (n = 23). Comorbid major depressive
      disorder (MDD) was diagnosed according to DSM-IV criteria using a semi-structured
      interview (SCID-I). Furthermore, depressive symptoms were assessed using Beck's
      depression inventory (BDI). Presence of MDD was not associated with elevated
      homocysteine levels (t-test: T = 0.42; df = 42; P = 0.68). However, self-rated
      presence of clinically relevant depressive symptoms (BDI score18) was associated
      with elevated homocysteine (T = -2.8; df = 42; P = 0.008). Presence of depressive
      symptoms may explain elevated homocysteine levels previously reported in patients
      with eating disorders or vice versa. Longitudinal studies are needed to unravel
      this hen or egg problem.

PMID- 17182058
TI  - Retinopathy as an indicator of silent brain infarction in asymptomatic
      hypertensive subjects.
AB  - BACKGROUND AND PURPOSE: Silent brain infarction (SBI), which is cerebral target
      organ damage of hypertensive microangiopathies, is frequently seen in
      hypertensive patients. The purpose of this study is to investigate the relation
      between hypertensive retinopathy (HTR) and SBI in subjects without a history of
      stroke or transient ischemic attack. METHODS: Five hundred-fifty hypertensive
      subjects without history of stroke or transient ischemic attack had brain MRI and
      retinal photographs taken. The presence of SBI was assessed from the MRI scans,
      which was defined as a lesion of at least 3 mm in diameter with typical imaging
      characteristics. The presence HTR was defined from digitized retinal photographs.
      RESULTS: Seventy-seven subjects (14%) showed HTR (grade 1 in 46, grade 2 in 31
      persons). A multivariate analysis showed that age (OR, 1.07; 95% CI, 1.03 to
      1.10) and HTR (OR, 2.01 for grade 1; OR, 3.03 for grade 2) were the independent
      indicators for the presence of SBI. The higher the grade of HTR, the more
      prevalent SBI than persons with normal retina (by linear by linear association
      test, p=0.001). CONCLUSION: HTR is associated with the presence of SBI. This
      finding suggests that retinal photography may be useful for identifying
      hypertensive subjects at increased risk of having SBI regardless of current blood
      pressure status.

PMID- 17182059
TI  - Epilepsy and antiepileptic drug use in elderly people as risk factors for
      dementia.
AB  - OBJECTIVE: To assess the role of epilepsy and antiepileptic drugs (AEDs) as risk
      factors for probable Alzheimer's disease (AD) and for all dementias in the
      Canadian Study of Health and Aging (CSHA). A secondary objective was to isolate
      the effect of the AED phenytoin on the development of dementia and AD. METHODS:
      The cohort consists of 5376 participants aged 65 years or older with no evidence
      of dementia, defined as Modified Mini-Mental State (3MS) score > or =78. Primary
      exposure was self-report or clinical diagnosis of epilepsy at baseline (n=39), or
      self-report of AED therapy (n=67). Primary outcomes were development of dementia,
      defined as 3MS<78, or AD, determined by clinical examination using standard
      criteria, during a 5-year follow-up period. People whose 3MS score remained > or
      =78 served as the comparison group. RESULTS: People reporting AED use at baseline
      had an age, sex and baseline 3MS adjusted odds ratio (OR) of 2.11 (95% CI 1.11 to
      4.01) for developing dementia compared to those not taking AEDs at baseline. The
      association remained significant using only phenytoin as the exposure. No
      significant association was found between AED use and development of AD, nor
      between epilepsy and development of either AD or dementia. CONCLUSIONS: Older
      adults taking AEDs are at a significantly higher relative risk of developing
      dementia than those not taking AEDs. Further investigation of this finding is
      warranted.

PMID- 17182060
TI  - An unusual late complication of intracerebral haematoma in herpes encephalitis
      after successful acyclovir treatment.
AB  - This is a case report of PCR proven herpes simplex (HSV-1) encephalitis in a 26
      years old immunocompetent adult taking an unusual course of acute intracerebral
      haematoma after successful and complete recovery with acyclovir therapy. This
      transient late complication was associated with a negative repeat CSF PCR for HSV
      suggesting that the initial 14 days course of acyclovir was successful in the
      eradication of the herpes virus infection as recommended by the International
      Herpes Management Forum (IHMF). The location of the haematoma corresponded to the
      initial encephalitic area involving the medial temporal lobe structures. Despite
      this late neuroradiologic complication, after day 18 of symptom onset, the
      patient had a favourable neurological outcome. To the best of our knowledge, this
      is the second report of the unusual, rare, and late neuroimaging complication of
      acute intracerebral haematoma formation after complete recovery from treated HSVE
      with favourable clinical outcome. The literature is reviewed and plausible
      aetiology is discussed.

PMID- 17182061
TI  - Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher
      disease patient and a carrier.
AB  - A clinical association between Gaucher disease and parkinsonism has been
      demonstrated. We herein report a Japanese patient with type 3 Gaucher disease who
      was compound heterozygous for F213I and L444P mutations in the glucocerebrosidase
      gene while his father was heterozygous for the L444P mutation. They both
      presented with parkinsonism characterized by a predominance of akinetic-rigid
      signs and a favorable response to anti-Parkinson therapies. We investigated the
      dopaminergic neuronal function using positron emission tomography (PET) with
      radioligands, [(11)C] CFT and [(11)C] raclopride. PET studies of both patients
      demonstrated the [(11)C] CFT uptake to be severely decreased in the putamen and
      the caudate nucleus, however, the [(11)C] raclopride uptake was normal in the
      basal ganglia. Although the majority of Gaucher disease patients with
      parkinsonism tend to be refractory to anti-Parkinson therapies. The clinical
      features and the findings of the PET studies suggest that patients with
      parkinsonism associated with the mutation in the glucocerebrosidase gene, even in
      heterozygosis, may be related to the presynaptic dopaminergic neuronal
      dysfunction reported in Parkinson's disease. A PET study to evaluate the
      dopaminergic neuronal function in Gaucher disease would provide both a better
      understanding of the effects of anti-Parkinson therapies and a help to improve
      our ability to make an early diagnosis of parkinsonism associated with Gaucher
      disease.

PMID- 17182062
TI  - Rapid diagnosis of tuberculous meningitis: a comparative evaluation of in-house
      PCR assays involving three mycobacterial DNA sequences, IS6110, MPB-64 and 65 kDa
      antigen.
AB  - A PCR was standardized for amplifying three different mycobacterial--IS6110, MPB
      64, 65 kDa DNA sequences. A comparative evaluation of the three PCR assays was
      carried out for the rapid diagnosis of tuberculous meningitis (TBM) using
      cerebrospinal fluid (CSF) specimens. While the IS6110 PCR was a single-step
      amplification reaction, the MPB-64 and 65 kDa antigen PCR assays were nested
      reactions. A total of 176 cerebrospinal fluid (CSF) samples from 176 patients
      were subjected to amplification of the three different mycobacterial sequences.
      Amongst them, 45 samples were obtained from confirmed cases of TBM (culture
      positive) and 56 samples were obtained from clinically suspected cases of TBM
      which were culture-negative. The remaining 75 CSF samples were categorized under
      the non-infectious and infectious illness of the central nervous system (CNS).
      Against a gold standard of culture, a sensitivity of 98% (NPV=99%) and a
      specificity of 100% (PPV=100%) was observed with the IS6110 PCR. Among the nested
      PCRs, a sensitivity of 91% (NPV=94%) and a specificity of 91% (PPV=85%) was
      observed with the MPB-64 assay, while the 65 kDa protocol had an associated
      sensitivity of 51% (NPV=76%) and a specificity of 92% (PPV=79%). These findings
      suggest that among the nested PCR assays, the MPB-64 PCR assay was associated
      with an enhanced degree of sensitivity and was comparable in terms of
      specificity. Our study also demonstrates that the IS6110 assay, while being a
      single-step PCR had the advantage of being a rapid test for the diagnosis of TBM,
      with increased sensitivity and enhanced specificity as compared to the nested PCR
      protocols.

PMID- 17182063
TI  - Evolution of indirect reciprocity in groups of various sizes and comparison with
      direct reciprocity.
AB  - Recently many studies have investigated the evolution of indirect reciprocity
      through which cooperative action is returned by a third individual, e.g.
      individual A helped B and then receives help from C. Most studies on indirect
      reciprocity have presumed that only two individuals take part in a single
      interaction (group), e.g. A helps B and C helps A. In this paper, we investigate
      the evolution of indirect reciprocity when more than two individuals take part in
      a single group, and compare the result with direct reciprocity through which
      cooperative action is directly returned by the recipient. Our analyses show the
      following. In the population with discriminating cooperators and unconditional
      defectors, whether implementation error is included or not, (i) both strategies
      are evolutionarily stable and the evolution of indirect reciprocity becomes more
      difficult as group size increases, and (ii) the condition for the evolution of
      indirect reciprocity under standing reputation criterion where the third
      individuals distinguish between justified and unjustified defections is more
      relaxed than that under image scoring reputation criterion in which the third
      individuals do not distinguish with. Furthermore, in the population that also
      includes unconditional cooperators, (iii) in the presence of errors in
      implementation, the discriminating strategy is evolutionarily stable not only
      under standing but also under image scoring if group size is larger than two.
      Finally, (iv) in the absence of errors in implementation, the condition for the
      evolution of direct reciprocity is equivalent to that for the evolution of
      indirect reciprocity under standing, and, in the presence of errors, the
      condition for the evolution of direct reciprocity is very close to that for the
      evolution of indirect reciprocity under image scoring.

PMID- 17182064
TI  - Size-structured demographic models of coral populations.
AB  - The demographic processes of growth, mortality, and the recruitment of young
      individuals, are the major organizing forces regulating communities in open
      systems. Here we present a size-structured (rather than age-structured)
      population model to examine the role of these different processes in space
      limited open systems, taking coral reefs as an example. In this flux-diffusion
      model the growth rate of corals depends both on the available free-space (i.e.
      density-dependence) and on the particular size of the coral. In our analysis we
      progressively study several different forms of growth rate functions to
      disentangle the effects of free space and size-dependence on the model's
      stability. Unlike Roughgarden et al. [1985. Demographic theory for an open marine
      population space-limited recruitment. Ecology 66(1), 54-67], whose principal
      result is that the growth of settled organisms is destabilizing, we find that
      size-dependent growth rate often has the potential to endow stability. This is
      particularly true, if the growth rate is dependent on available free space (i.e.
      density dependent), but examples are given for growth rates that even lack this
      property. Further insights into reef system fragility are found through studying
      the sensitivity of the model steady state to changes in recruitment.

PMID- 17182065
TI  - S-allylcysteine ameliorates isoproterenol-induced cardiac toxicity in rats by
      stabilizing cardiac mitochondrial and lysosomal enzymes.
AB  - This study was aimed to evaluate the preventive role of S-allylcysteine (SAC) on
      mitochondrial and lysosomal enzymes in isoproterenol (ISO)-induced rats. Male
      albino Wistar rats were pretreated with SAC (50, 100 and 150 mg/kg) daily for a
      period of 45 days. After the treatment period, ISO (150 mg/kg) was subcutaneously
      injected to rats at an interval of 24 h for two days. The activities of heart
      mitochondrial enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate
      dehydrogenase and alpha-ketoglutarate dehydrogenase) and respiratory chain
      enzymes (NADH dehydrogenase and cytochrome C oxidase) were decreased
      significantly (p<0.05) in ISO-induced rats. The activities of lysosomal enzymes
      (beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, cathepsin
      D and acid phosphatase) were increased significantly (p<0.05) in serum and heart
      of ISO-induced rats. Pretreatment with SAC (100 mg/kg and 150 mg/kg) for a period
      of 45 days increased significantly (p<0.05) the activities of mitochondrial and
      respiratory chain enzymes and decreased the activities of lysosomal enzymes
      significantly (p<0.05) in ISO-induced rats. Oral administration of SAC (50, 100
      and 150 mg/kg) for a period of 45 days to normal rats did not show any
      significant (p<0.05) effect in all the parameters studied. The altered
      electrocardiogram (ECG) of ISO-treated rats was also restored to near normal by
      treatment with SAC (100 and 150 mg/kg). These results confirm the efficacy of SAC
      in alleviating ISO-induced cardiac damage.

PMID- 17182066
TI  - Taiwanin A induced cell cycle arrest and p53-dependent apoptosis in human
      hepatocellular carcinoma HepG2 cells.
AB  - Taiwanin A, a lignan isolated from Taiwania cryptomerioides Hayata, has
      previously been reported to have cytotoxicity against human tumor cells, but the
      mechanisms are unclear. In this study, we examined the molecular mechanism of
      cell death of human hepatocellular carcinoma HepG2 cells induced by Taiwanin A.
      Taiwanin A has been found to induce cell cycle arrest at G2/M phase as well as
      caspase-3-dependent apoptosis within 24 h. We performed both in vitro turbidity
      assay and immunofluorescence staining of tubulin to show that Taiwanin A can
      inhibit microtubule assembly. Moreover, the tumor suppressor protein p53 in HepG2
      cells was activated by Taiwanin A within 12 h. Inhibition of p53 by either
      pifithrin-alpha or by short hairpin RNA which blocks p53 expression attenuates
      Taiwanin A cytotoxicity. Our results demonstrate that Taiwanin A can act as a new
      class of microtubule damaging agent, arresting cell cycle progression at mitotic
      phase and inducing apoptosis through the activation of p53.

PMID- 17182067
TI  - Stress and welfare: two complementary concepts that are intrinsically related to
      the animal's point of view.
AB  - The closely associated concepts of welfare and stress may be considered as
      opposites since welfare cannot be achieved under stress and vice versa. Stress
      was first considered as an unspecific response to any challenge taxing the
      organism's resources where the HPA axis plays a central role [Selye H. A syndrome
      produced by diverse nocuous agents. Nature 1936:32]. Along the same lines,
      welfare was considered as the state of an individual on a continuum between poor
      and good depending on the efforts required to adapt to the environment [Broom DM.
      Animal welfare: concepts and measurement. J Anim Sci 1991;69:4167-75]. However,
      these views cannot explain opposite results such as up- vs. down-regulation of
      the HPA axis and hypo- vs. hyper-behavioural reactivity under chronic stress.
      Later, it was shown that aversive situations trigger stress responses only if the
      individual perceives them as aversive. Mason [Mason JW. A re-evaluation of the
      concept of 'non-specificity' in stress theory. J Psychiatr Res 1971;8:323-33]
      suggested that the unspecificity of stress responses originates from a common
      emotion that produces them. Welfare has also been defined in terms of emotional
      states by Dawkins [Dawkins MS. Animal suffering, the science of animal welfare.
      London: Chapman and Hall Ltd.; 1980] and Duncan [Duncan IJH. Welfare is to do
      with what animals feel. J Agric Environ Ethics 1993;6:8-14]. Hence, both concepts
      are linked to mental states. Recent advances in psychology suggest that the very
      nature of an emotion results from a series of evaluations of the triggering
      situation that the individual makes based on criteria including novelty,
      predictability, controllability, and others [Scherer KR. Appraisal considered as
      a process of multi-level sequential checking. In: Scherer KR, Schorr A, Johnstone
      T, editors. Appraisal processes in emotion: theory, methods, research. New York:
      Oxford University Press; 2001. p. 92-120]. It is therefore suggested that the
      discrepancies found in the literature in terms of responses of the HPA axis or
      modification of behaviour under aversive conditions may stem from differences in
      the way a situation is evaluated. It is argued that stress comes from the
      animal's evaluation of the outcome of a situation, and that welfare is the state
      resulting from that evaluation.

PMID- 17182069
TI  - Covalent anthocyanin-flavone dimer from leaves of Oxalis triangularis.
AB  - The anthocyanin-flavone C-glycoside, (malvidin 3-O-(6(II)-O-alpha
      rhamnopyranosyl(AIV)-beta-glucopyranoside(AII))-5-O-beta-glucopyranoside(AIII))
      (apigenin 6-C-(2(II)-O-beta-glucopyranosyl(FIII)-beta-glucopyranoside(FII)))
      malonate(AV) (A(IV)-4-->A(V)-1, F(III)-6-->A(V)-3) (1), has been isolated from
      leaves of Oxalis triangularis A. St.-Hil. In the 1D (1)H NMR spectrum of 1
      dissolved in CD(3)OD-CF(3)CO(2)D (95:5), MTFA, recorded 45 min after sample
      preparation, this covalently linked dimer occurred mainly as flavylium cation
      (38%) and two equilibrium forms assigned to be quinonoidal bases (54%), whereas
      only minor amounts of the hemiacetal forms were present. After five days storage
      at 300 K, the hemiacetals (39%) and flavylium cation (38%) constituted the main
      forms of 1. More simple anthocyanins are normally considered to be on the
      flavylium cation form in acidified deuterated methanol. The cross-peaks observed
      in NOESY NMR spectra of 1 indicated the presence of vertical 'pi-pi' stacking
      between the B-ring of the flavone unit and the A-ring of each of the two forms
      assigned to be quinonoidal bases. It was not possible to discriminate between
      inter- or intramolecular association mechanisms. The equilibria between the
      various forms of 1 were studied by two-dimensional NOESY and ROESY NMR
      spectroscopy. 2D HSQC-TOCSY NMR spectroscopy was among the methods used for
      characterization of the various forms.

PMID- 17182068
TI  - Stereoisomeric pattern of lilac aldehyde in Silene latifolia, a plant involved in
      a nursery pollination system.
AB  - The monoterpene lilac aldehyde is found in floral scent of several plants
      species, among them Silene latifolia. This plant is involved in a nursery
      pollination system, because a noctuid moth, Hadena bicruris, is not only
      pollinator but also seed predator. Lilac aldehyde is the key floral scent
      compound of S. latifolia for attracting Hadena. This monoterpene has three
      stereogenic centers, and eight different isomers are possible. Here, we analysed
      the ratio of lilac aldehyde isomers from plants originating from 18 different
      populations of S. latifolia using enantioselective multidimensional GC-MS
      (enantio-MDGC-MS), and compared resulting variability with variability found in
      total scent emitted by specimen under study. Though variability in total emitted
      scent was high, ratio of lilac aldehyde isomers was a more conservative trait.
      There was no correlation between the ratio of lilac aldehyde isomers and the
      total emitted floral scent pattern. Both, ratio of stereoisomers and total
      emitted scent were independent from the geographic origin of the plants. In
      conclusion, the ratio of lilac aldehyde stereoisomers in S. latifolia is a
      reliable trait, and may used by the nursery pollinator H. bicruris for host-plant
      detection.

PMID- 17182070
TI  - Does an apple a day keep the doctor away because a phytoestrogen a day keeps the
      virus at bay? A review of the anti-viral properties of phytoestrogens.
AB  - From dengue to herpes and influenza to AIDS, the phytoestrogens that are present
      in many fruits and vegetables have been shown to exert anti-viral properties.
      Here we review the various different anti-viral mechanisms employed by
      phytoestrogens.

PMID- 17182071
TI  - Health status of returnees to Kosovo: do living conditions during asylum make a
      difference?
AB  - OBJECTIVE: From August 1999 to July 2001, asylum seekers who had come to
      Switzerland from Kosovo were repatriated. The present study aimed to assess the
      relationship between living conditions during asylum in Switzerland and health
      status among returnees. STUDY DESIGN: Cross-sectional survey of 319 ethnic
      Albanian families in Kosovo, selected from a list of 12900 heads of households
      who had received repatriation aid. METHODS: Consenting household members aged 16
      years or more who had received asylum in Switzerland were interviewed during the
      autumn of 2001. Questions explored living conditions during asylum, present socio
      economic conditions (World Bank Kosovo Poverty Assessment Survey), subjective
      physical and mental health [Medical Outcomes Study 36-item Short Form Health
      Survey (SF-36)], traumatic events (Harvard Trauma Questionnaire) and symptoms of
      post-traumatic stress disorder (PTSD; Mini International Neuropsychiatric
      Interview). RESULTS: Ninety-four per cent of selected households were located.
      Among the 580 participants, 25.5% suffered from PTSD and 65% lived in extreme
      poverty. Subjective health scores, measured by SF-36, were low, particularly for
      those affected by PTSD. Among living conditions in the host country, duration of
      stay longer than 26 weeks was associated with lower mental health scores,
      particularly among people with PTSD. CONCLUSIONS: Two years after the conflict,
      returnees had low health scores. The association between duration of stay and
      lower mental health scores may reflect the stress of adapting to asylum or the
      consequence of compulsory repatriation. This study has implications for the
      emerging healthcare system in Kosovo and for policies of asylum in host
      countries.

PMID- 17182072
TI  - Theanaphthoquinone inhibits fatty acid synthase expression in EGF-stimulated
      human breast cancer cells via the regulation of EGFR/ErbB-2 signaling.
AB  - Fatty acid synthase (FAS) is a major lipogenic enzyme catalyzing the synthesis of
      long-chain saturated fatty acids. Most breast cancers require lipogenesis for
      growth. Here, we demonstrated the effects of theanaphthoquinone (TNQ), a member
      of the thearubigins generated by the oxidation of theaflavin (TF-1), on the
      expression of FAS in human breast cancer cells. TNQ was found to suppress the EGF
      induced expression of FAS mRNA and FAS protein in MDA-MB-231 cells. Expression of
      FAS has previously been shown to be regulated by the SREBP family of
      transcription factors. In this study, we demonstrated that the EGF-induced
      nuclear translocation of SREBP-1 was blocked by TNQ. Moreover, TNQ also modulated
      EGF-induced ERK1/2 and Akt phosphorylation. Treatment of MDA-MB-231 cells with PI
      3-kinase inhibitors, LY294002 and Wortmannin, inhibited the EGF-induced
      expression of FAS and nuclear translocation of SREBP-1. Treatment with TNQ
      inhibited EGF-induced EGFR/ErbB-2 phosphorylation and dimerization. Furthermore,
      treatment with kinase inhibitors of EGFR and ErbB-2 suggested that EGFR/ErbB-2
      activation was involved in EGF-induced FAS expression. In constitutive FAS
      expression, TNQ inhibited FAS expression and Akt autophosphorylation in BT-474
      cells. The PI 3-kinase inhibitors and tyrosine kinase inhibitors of EGFR and ErbB
      2 also reduced constitutive FAS expression. In addition, pharmacological blockade
      of FAS by TNQ decreased cell viability and induced cell death in BT-474 cells. In
      summary, our findings suggest that TNQ modulates FAS expression by the regulation
      of EGFR/ErbB-2 pathways and induces cell death in breast cancer cells.

PMID- 17182073
TI  - Comparative effects of the toxic dinoflagellate Karenia brevis on clearance rates
      in juveniles of four bivalve molluscs from Florida, USA.
AB  - The effects of Karenia brevis (Gymnodiniales, Gymnodiniaceae) on the feeding
      activity of juveniles of four species of bivalve mollusc were examined in the
      laboratory to assess the potential impacts on these important shellfish
      populations from Florida. Clearance rates were determined under short-term (one
      hour) static and long-term (two days) flow-through conditions using both whole
      and lysed cultures of K. brevis. Under short-term conditions, the bay scallop,
      Argopecten irradians, was the most sensitive species, exhibiting a 79% reduction
      in clearance rate at 1000 cells ml(-1) of whole K. brevis culture compared to the
      control (no K. brevis). The eastern oyster, Crassostrea virginica, was the least
      responsive, showing a 38% reduction in clearance rate between the same
      treatments. The green mussel, Perna viridis, and the northern quahog, Mercenaria
      mercenaria, displayed intermediate responses. Similar results were also observed
      during long-term exposures to a continuous supply of K. brevis. Bay scallops
      showed a significant decline in clearance rate at 100 cells ml(-1) after 24h
      exposure; clearance rate of oysters was not affected by K. brevis at this
      concentration. No mortality was observed for any species during these brief
      exposures. The prospect for recovery of bay scallop populations in Florida
      estuaries where they were once abundant may be hampered by recurring blooms of K.
      brevis. Reduced clearance rates in M. mercenaria at high K. brevis densities
      could translate into poor growth of cultured Florida hard clams. On the other
      hand, P. viridis, which also showed reduced clearance rates at high K. brevis
      concentrations, might be negatively impacted by K. brevis blooms, thereby
      affecting their ability to spread into estuaries hampered by recurring toxic
      algal blooms.

PMID- 17182075
TI  - Temporal frequency and contrast tagging bias the type of competition in
      interocular switch rivalry.
AB  - The nature of competition underlying perceptual alternations in binocular rivalry
      remains controversial. Interocular swapping of rivalrous stimuli can result in
      either slow irregular perceptual alternations that bridge multiple interocular
      switches or fast regular alternations that are time locked to the stimulus
      exchanges. We labeled either the inputs to the eyes or the individual rivalrous
      stimuli using temporal frequency and contrast tagging. Tagging of eye-of-origin
      signals enhanced the fast regular perceptual alternations associated with eye
      rivalry, while stimulus tagging shifted perception towards slow irregular
      alternations characteristic of stimulus rivalry. Thus, the type of competition in
      binocular rivalry can be biased based on additional cues in the visual inputs.
      The results are consistent with a model in which the brain combines information
      across multiple visual features to resolve ambiguities in visual inputs.

PMID- 17182074
TI  - The conserved His8 of the Moloney murine leukemia virus Env SU subunit directs
      the activity of the SU-TM disulphide bond isomerase.
AB  - Murine leukemia virus (MLV) fusion is controlled by isomerization of the
      disulphide bond between the receptor-binding surface (SU) and fusion-active
      transmembrane subunits of the Env-complex. The bond is in SU linked to a CXXC
      motif. This carries a free thiol that upon receptor binding can be activated
      (ionized) to attack the disulphide and rearrange it into a disulphide isomer
      within the motif. To find out whether His8 in the conserved SPHQ sequence of Env
      directs thiol activation, we analyzed its ionization in MLV vectors with wtEnv
      and Env with His8 deleted or substituted for Tyr or Arg, which partially or
      completely arrests fusion. The ionization was monitored by following the pH
      effect on isomerization in vitro by Ca2+ depletion or in vivo by receptor
      binding. We found that wtEnv isomerized optimally at slightly basic pH whereas
      the partially active mutant required higher and the inactive mutants still higher
      pH. This suggests that His8 directs the ionization of the CXXC thiol.

PMID- 17182076
TI  - Chromium(VI) resistance and removal by actinomycete strains isolated from
      sediments.
AB  - Forty-one isolated actinomycetes were used to study qualitative and semi
      quantitative screening of chromium(VI) resistance. Chromate-removing activity was
      estimated using the Cr(VI) specific colorimetric reagent 1,5-diphenylcarbazide.
      Twenty percent of the isolates from El Cadillal (EC) and 14% of isolates from a
      copper filter plant (CFP) were able to grow at 13 mM of Cr(VI). All isolates from
      sugar cane (SCP) could grow up to Cr(VI) concentration of 17 mM. EC, CFP and SCP
      strains were able to remove 24%, 30% and more than 40% of Cr(VI), respectively.
      The highest and lowest Cr(VI) specific removal values were 75.5 mg g(-1) cell by
      M3 (CFP), and 1.5 mg g(-1) cell by C35 (EC) strains. Eleven Cr(VI) resistant
      strains were characterized and identified as species of the genera Streptomyces
      (10) and Amycolatopsis (1). Differences on actinomycete community composition
      between contaminated and non-contaminated soil were found. This study showed the
      potential capacity of actinomycetes as tools for Cr(VI) bioremediation.

PMID- 17182077
TI  - Microbially mediated cadmium sorption/desorption processes in soil amended with
      sewage sludge.
AB  - A multi-compartment system was used to study the importance of microorganisms for
      Cd desorption from soil amended with sewage sludge and simultaneous resorption of
      the mobilized metal by soil constituents. Using this system made it possible to
      study the participation of microorganisms (Arthrobacter, Trichoderma),
      montmorillonite, humic acids, and iron oxides in resorption of the released Cd. A
      filter-sterilized water extract of root-free soil of pH 6.7 (RF) or RF
      supplemented with glucose (RFG) were used to mobilize Cd from soil at 14 degrees
      C in 48 h. Cadmium found in those extracts after 48-h incubation was recognized
      as bioavailable. Changes in pH values and enrichment of soil extracts with
      organic acids and siderophores resulted from microbial growth. RFG with lower pH
      and a higher content of ligands mobilized, on average, 40% of Cd introduced with
      sewage sludge amended soil, whereas RF mobilized only 20% of it. Sequential
      extractions of Cd at time 0 and Cd remaining in soil showed that RFG had
      mobilized Cd mostly from the fraction bound with Fe and Mn oxides. Microbial
      biomass accounted for only up to 3.4% (w/w) of the soil constituents used in the
      experiments but resorbed 25% of mobilized Cd. The chemical composition of
      mobilizing soil extracts and the solid-to-mobilizing-extracts volume ratio had a
      significant effect on the amount of bioavailable Cd. The results of the study
      suggest that microbial metabolites were involved in Cd mobilization, while the
      biomass of microorganisms was involved in Cd resorption as a biosorbent.

PMID- 17182078
TI  - Mutagenicity evaluation of industrial sludge from common effluent treatment
      plant.
AB  - Sludge from common effluent treatment plant (CETP) receiving effluents from
      textile industries at Mandia Road, Pali, was analyzed to assess the level of
      mutagenicity. Mutagenicity assay using Salmonella typhimurium tester strains TA
      98 and TA 100 gave positive results, thus suggesting presence of genotoxic
      contaminants in the samples investigated. Further, mutagenic activity of chemical
      sludge was found to be lesser than that of biological sludge. This result is very
      surprising and unexpected as it is indicating that some mutagenic compounds are
      either being formed or certain promutagenic compounds are being converted into
      stable mutagenic metabolites during the biological treatment of the wastewater
      effluents. There have been no previous reports giving similar or contrary
      results. Most of the previous studies have reported effects of single combined
      sludge.

PMID- 17182079
TI  - Inhibition of heavy metals on fermentative hydrogen production by granular
      sludge.
AB  - This study was conducted to investigate the toxicity of six electroplating metals
      on the H(2)-producing activity of a granular sludge sampled from an H(2)
      producing upflow reactor treating sucrose-containing wastewater. The H(2)
      production activities of the sludge were measured in serum vials using wastewater
      containing not just sucrose and proper nutrient, but also individual heavy metals
      at concentrations ranging 0-5000 mg l(-1). The relative toxicity to H(2)
      production was found in the following order: Cu (most toxic)>>Ni approximately
      Zn>Cr>Cd>Pb (least toxic). The C(I,50) values, at which the bioactivity of the
      sludge was reduced to 50% of the control, for individual heavy metals were Cu 30
      mg l(-1), Ni and Zn 1600 mg l(-1), Cr 3000 mg l(-1), Cd 3500 mg l(-1), and Pb
      >5000 mg l(-1). Compared with the literature data, H(2)-producing sludge
      exhibited in general higher resistance to metal toxicity than methanogenic
      granular sludge.

PMID- 17182080
TI  - Excess copper induced physiological and proteomic changes in germinating rice
      seeds.
AB  - Copper is an essential micronutrient for plants. Present at a high concentration
      in soil, copper is also regarded as a major toxicant to plant cells due to its
      potential inhibitory effects against many physiological and biochemical
      processes. The interference of germination-related proteins by heavy metals has
      not been well documented at the proteomic level. In the current study,
      physiological, biochemical and proteomic changes of germinating rice seeds were
      investigated under copper stress. Germination rate, shoot elongation, plant
      biomass, and water content were decreased, whereas accumulation of copper and
      TBARS content in seeds were increased significantly with increasing copper
      concentrations from 0.2mM to 1.5mM followed by germination. The SDS-PAGE showed
      the preliminary changes in the polypeptides patterns under copper stress. Protein
      profiles analyzed by two-dimensional electrophoresis (2-DE) revealed that 25
      protein spots were differentially expressed in copper-treated samples. Among
      them, 18 protein spots were up-regulated and 7 protein spots were down-regulated.
      These differentially displayed proteins were identified by MALDI-TOF mass
      spectrometry. The up-regulation of some antioxidant and stress-related proteins
      such as glyoxalase I, peroxiredoxin, aldose reductase, and some regulatory
      proteins such as DnaK-type molecular chaperone, UlpI protease, and receptor-like
      kinase clearly indicated that excess copper generates oxidative stress that might
      be disruptive to other important metabolic processes. Moreover, down-regulation
      of key metabolic enzymes like alpha-amylase or enolase revealed that the
      inhibition of seed germinations after exposure to excess copper not only affects
      starvation in water uptake by seeds but also results in failure in the reserve
      mobilization processes. These results indicate a good correlation between the
      physiological and biochemical changes in germinating rice seeds exposed to excess
      copper.

PMID- 17182081
TI  - Uptake and loss of dissolved 109Cd and 75Se in estuarine macroinvertebrates.
AB  - Semaphore crabs (Heloecius cordiformis), soldier crabs (Mictyris platycheles),
      ghost shrimps (Trypaea australiensis), pygmy mussels (Xenostrobus securis), and
      polychaetes (Eunice sp.), key benthic prey items of predatory fish commonly found
      in estuaries throughout southeastern Australia, were exposed to dissolved (109)Cd
      and (75)Se for 385 h at 30 k Bq/l (uptake phase), followed by exposure to
      radionuclide-free water for 189 h (loss phase). The whole body uptake rates of
      (75)Se by pygmy mussels, semaphore crabs and soldier crabs were 1.9, 2.4 and 4.1
      times higher than (109)Cd, respectively. There were no significant (P>0.05)
      differences between the uptake rates of (75)Se and (109)Cd for ghost shrimps and
      polychaetes. The uptake rates of (109)Cd and (75)Se were highest in pygmy
      mussels; about six times higher than in soldier crabs for (109)Cd and in
      polychaetes for (75)Se - the organisms with the lowest uptake rates. The loss
      rates of (109)Cd and (75)Se were highest in semaphore crabs; about four times
      higher than in polychaetes for (109)Cd and nine times higher than in ghost
      shrimps for (75)Se - the organisms with the lowest loss rates. The loss of
      (109)Cd and (75)Se in all organisms was best described by a two (i.e. short and a
      longer-lived) compartment model. In the short-lived, or rapidly exchanging,
      compartment, the biological half-lives of (75)Se (16-39 h) were about three times
      greater than those of (109)Cd (5-12h). In contrast, the biological half-lives of
      (109)Cd in the longer-lived, or slowly exchanging compartment(s), were typically
      greater (1370-5950 h) than those of (75)Se (161-1500 h). Semaphore crabs had the
      shortest biological half-lives of both radionuclides in the long-lived
      compartment, whereas polychaetes had the greatest biological half-life for
      (109)Cd (5950 h), and ghost shrimps had the greatest biological half-life for
      (75)Se (1500 h). This study provides the first reported data for the biological
      half-lives of Se in estuarine decapod crustaceans. Moreover, it emphasises the
      importance of determining metal(loid) accumulation and loss kinetics in keystone
      prey items, which consequently influences their trophic transfer potential to
      higher-order predators.

PMID- 17182082
TI  - Daytime resolved analysis of polycyclic aromatic hydrocarbons in urban aerosol
      samples - impact of sources and meteorological conditions.
AB  - Urban aerosol was collected in a summer and a winter campaign for 7 and 3 days,
      respectively. Low volume samples were taken with a time resolution of 160 min
      using a filter/sorption cartridge system extended by an ozone scrubber.
      Concentrations of mainly particle associated polycyclic aromatic hydrocarbons
      (PAH) and oxidised PAH (O-PAH) were determined by gas chromatography/high
      resolution mass spectrometry. The sampling site was located in the city centre of
      Augsburg, Germany, near major roads with high traffic volume. The daily
      concentrations and profiles were mainly governed by local emissions from traffic
      and domestic heating, as well as by the meteorological conditions. During the
      winter campaign, concentrations were more than 10 fold higher than during the
      summer campaign. Highest concentrations were found concurrent with low boundary
      layer heights and low wind speeds. Significant diurnal variation of the PAH
      profiles was observed. Enhanced influences of traffic related PAH on the PAH
      profiles were evident during daytime in summer, whereas emissions from hot water
      generation and domestic heating were obvious during the night time of both
      seasons. A general idea about the global meteorological situation was acquired
      using back trajectory calculations (NOAA ARL HYSPLIT4). Due to high local
      emissions in combination with low air exchange during the two sampling campaigns,
      effects of mesoscale transport were not clearly observable.

PMID- 17182083
TI  - Effects of coal combustion residues on survival, antioxidant potential, and
      genotoxicity resulting from full-lifecycle exposure of grass shrimp (Palaemonetes
      pugio Holthius).
AB  - Coal combustion residues (CCRs), largely derived from coal-fired electrical
      generation, are rich in numerous trace elements that have the potential to induce
      sublethal effects including oxidative stress, alterations in antioxidant status
      and DNA single strand breaks (SSB). CCRs are frequently discharged into natural
      and man-made aquatic systems. As the effects of CCRs have received relatively
      little attention in estuarine systems, the estuarine grass shrimp, Palaemonetes
      pugio, was chosen for this study. Grass shrimp were exposed in the laboratory to
      CCR-enriched sediments and food over a full life cycle. Survival to metamorphosis
      was significantly reduced in CCR-exposed larvae (17+/-4 versus 70+/-13% in the
      controls) but not in the juveniles or adults. The COMET assay, a general but
      sensitive assay for genotoxicity, was used to quantify DNA SSB in the adults.
      Total antioxidant potential was examined to assess the overall antioxidant
      scavenging capacity of CCR-exposed and non-exposed adult grass shrimp. Grass
      shrimp exposed to CCR significantly accumulated selenium and cadmium compared to
      unexposed shrimp, although an inverse relationship was seen for mercury
      accumulation. Chronic CCR exposure caused DNA SSB in hepatopancreas cells, as
      evidenced by the significantly increased percent tail DNA, tail moment, and tail
      length as compared to reference shrimp. However, no significant difference was
      observed in total antioxidant potential. Our findings suggest that genotoxicity
      may be an important mode of toxicity of CCR, and that DNA SSB may serve as a
      useful biomarker of exposure and effect of this very common, complex waste
      stream.

PMID- 17182084
TI  - Changes in carbohydrate metabolism in fine roots of the native European black
      poplar (Populus nigra L.) in a heavy-metal-polluted environment.
AB  - Effects of copper-smelter-related deposition of heavy metals in the soil on
      carbohydrate metabolism of fine roots of the native European black poplar were
      investigated in spring and autumn. Total soluble non-structural carbohydrates in
      fine roots from trees growing in the polluted habitat were lower than in a
      control site, but this was directly associated only with a lower raffinose
      concentration. Neither glucose nor fructose concentrations differed significantly
      between polluted and unpolluted sites. In contrast, the galactose concentration
      was higher in the presence of heavy metals, especially in autumn. Also the
      stachyose concentration was higher in the polluted site, but only in autumn,
      suggesting it could be an alternative way of detoxification of galactose. No
      difference between control and polluted stands was observed in sucrose
      concentration. However, estimates of sucrolytic activity revealed markedly higher
      activities of sucrose synthase (SuSy), soluble acid (AI) and neutral (NI)
      invertases in the polluted stand than in the control. In contrast, the estimated
      glycolytic enzyme activities were not affected by the presence of heavy metals in
      soil.

PMID- 17182085
TI  - Osteosclerosis due to endemic fluorosis.
AB  - Endemic water borne fluorosis is a public health problem in Isparta, a city
      located in southern Turkey. In order to investigate the association between
      osteosclerosis and fluorosis, we retrospectively screened the results of lumbar
      spine and femur neck bone mineral density (BMD) of 1500 patients who were
      examined before, for any reason in between 2001-2003. Sixty nine patients (67
      females and 2 males, mean age 52.6+/-10.2) with vertebra T-scores>or=+2 were
      found only except a patient with osteoid osteoma in the femur neck (femur T
      score+6.64). Thirty-four of the patients could be reexamined with lateral
      vertebra BMD and investigated for fluorosis and the other etiologic causes of
      osteosclerosis. Of 34 patients, 14 had either mottled tooth enamel or urine
      fluoride level greater than 1.5 mg/l. Other etiologic causes were hypothyroidism
      (2), hypoparathyroidism (1), history of lumbar fracture (1), use of retinoids
      (1), vitamin D (7), oral calcium preparations (9), and bisphosphanates (3).
      Lateral lumbar vertebral T-score was greater than+2 in 12 patients (35.3%). Femur
      T-score was greater than+2 in 7 patients (20.6%). Fourteen patients (41.2%) had
      lateral vertebral or femur T-score>or=+2. Five (35.7%) of these patients had
      signs of fluorosis, as discussed before. Mean body mass index of individuals with
      fluorosis was 36.4+/-7.9 and this result was significantly higher than other
      osteosclerotic subjects (31.6+/-4.4). In conclusion we believe that approximately
      one third of the osteosclerosis in our region was due to endemic skeletal
      fluorosis and obesity may enhance this osteosclerotic type bone changes in
      endemic fluorosis.

PMID- 17182086
TI  - Metals and organochlorine pesticides in caudal scutes of crocodiles from Belize
      and Costa Rica.
AB  - Despite high animal diversity in the Neotropics and the largely unregulated use
      and disposal of pesticides and industrial chemicals in Central America, few data
      exist regarding accumulation of environmental contaminants in Central American
      wildlife. In this study we examined accumulation of metals and organochlorine
      (OC) pesticides in caudal scutes of crocodiles from Belize and Costa Rica. Scutes
      from Morelet's crocodiles (Crocodylus moreletii) from two sites in northern
      Belize were analyzed for metals, and scutes from American crocodiles (C. acutus)
      from one site in Costa Rica were analyzed for metals and OC pesticides. All
      scutes (n=25; one scute from each of 25 individuals) contained multiple
      contaminants. Mercury was the predominant metal detected, occurring in all scutes
      examined from both species. Other metals detected include cadmium, copper, lead,
      and zinc. American crocodile scutes from Costa Rica contained multiple OC
      pesticides, including endrin, methoxychlor, p,p'-DDE, and p,p'-DDT, all of which
      occurred in 100% of scutes analyzed (n=6). Mean metal and OC concentrations
      varied in relation to those previously reported in crocodilian scutes from other
      localities in North, Central, and South America. OC concentrations in American
      crocodile scutes were generally higher than those previously reported for other
      Costa Rican wildlife. Currently, caudal scutes may serve as general, non-lethal
      indicators of contaminant accumulation in crocodilians and their areas of
      occurrence. However, a better understanding of the relationships between
      pollutant concentrations in scutes, internal tissues, and environmental matrices
      at sample collection sites are needed to improve the utility of scutes in future
      ecotoxicological investigations.

PMID- 17182087
TI  - Design of a monitoring network and assessment of the pollution on the Lerma river
      and its tributaries by wastewaters disposal.
AB  - While the 2005 progress report of the United Nations Millennium Development Goals
      stresses out the need of a dramatic increase in investment to meet the sanitation
      target in the third world, it is important to anticipate about some parallel
      negative impacts that may have this optimistic programme (extension of sewer
      networks without sufficient treatment works). Research was initiated on Lerma
      River (Mexico), subjected to many rejects disposal, to design a monitoring
      network and evaluate the impact of wastewaters on its water quality. The
      discharges was inventorized, geo-positioned with a GPS and mapped, while the
      physico-chemical characteristics of the river water, its tributaries and main
      rejects were evaluated. Microtox system was used as an additional screening tool.
      Along the 60 km of the High Course of Lerma River (HCLR), 51 discharges, with a
      diameter or width larger than 0.3 m (including 7 small tributaries) were
      identified. Based on the inventory, a monitoring network of 21 sampling stations
      in the river and 13 in the important discharges (>2 m) was proposed. A great
      similitude was found between the average characteristics of the discharges and
      the river itself, in both the wet and dry seasons. Oxygen was found exhausted
      (<0.5 mg/L) almost all along the high course of the river, with COD and TDS
      average levels of 390 and 1980 mg/L in the dry season, against 150 and 400 mg/L
      in the wet season. In the dry season, almost all the sites along the river
      revealed some toxicity to the bacteria test species (2.9 to 150 TU, with an
      average of 27 TU). Same septic conditions and toxicity levels were observed in
      many of the discharges. Four of the six evaluated tributaries, as well as the
      lagoon (origin of the river), were relatively in better conditions (2 to 8 mg/L
      D.O., TU<1) than for the Lerma, acting as diluents and renewal of the HCLR flow
      rate. The river was shown to be quite a main sewer collector. The high surface
      water contamination by untreated wastewaters that is depicted in this research
      should be taken into account in the Millennium Goals strategies, by promoting
      treatment plan works simultaneously, when sewer networks in the third world would
      extend.

PMID- 17182088
TI  - Spatial variation in concentrations of dissolved nitrogen species in an upland
      blanket peat catchment.
AB  - The concentration of nitrogen (N), particularly as nitrate (NO3-N), in upland
      streams, lakes and rivers is frequently used as a diagnostic of the vulnerability
      of upland ecosystems to increased atmospheric nitrogen deposition and N
      saturation. The N content of running waters, however, is generally assessed on
      the basis of sampling at a limited number of points in space and time within the
      catchment under investigation. The current study was conducted at Trout Beck, an
      11.5 km2 blanket peat-dominated catchment in the North Pennine uplands of the UK.
      Results from sampling at 33 sites within this catchment demonstrated that the
      concentrations of all dissolved N species were highly variable, even over short
      distances. Statistical relationships between the concentrations of NO3-N and
      dissolved organic nitrogen (DON) and percentage catchment cover of
      Calluna/Eriophorum and Eriophorum vegetation were found. However, it was also
      noted that in catchments containing limestone outcrops, NO3-N concentration was
      much higher than in catchments where runoff was sourced directly from the blanket
      peat surface. It is possible that NH4-N and DON leached from the blanket peat are
      mineralised and nitrified, providing a source for the NO3-N found in the river
      channels. Overall, the current study suggests that interpretations of N
      saturation based on river water chemistry measurements at a single point must be
      treated cautiously, and that the influence of catchment-scale physical factors,
      such as vegetation and geology cover on the concentration of dissolved N species
      in upland river waters should not be ignored.

PMID- 17182089
TI  - Extended pelvic resection of iliacus muscle and femoral nerve for isolated
      recurrent uterine cancer.

PMID- 17182090
TI  - Effects of the CRF1 antagonist antalarmin on cocaine self-administration and
      discrimination in rhesus monkeys.
AB  - Cocaine stimulates the rapid release of ACTH, and by inference, CRF in several
      species, suggesting that the HPA "stress" axis may contribute to the abuse
      related effects of cocaine. The effects of a systemically-active CRF(1) receptor
      antagonist, antalarmin, on cocaine self-administration and cocaine discrimination
      were examined in rhesus monkeys. Antalarmin's acute (1-10 mg/kg, IV) and chronic
      (3.2 mg/kg IV) effects on IV cocaine self-administration were studied. The acute
      effects of 3.2 mg/kg IV antalarmin on the cocaine self-administration dose-effect
      curve (0.001-0.10 mg/kg/inj) were also examined. The acute effects of antalarmin
      (5 and 10 mg/kg, IM) on the cocaine discrimination dose-effect curve (0.013-1.3
      mg/kg) were examined. Antalarmin did not significantly decrease the reinforcing
      or the discriminative stimulus effects of cocaine. Acute antalarmin
      administration produced a dose-dependent but non-significant decrease in self
      administration of 0.01 mg/kg/inj cocaine but did not alter the cocaine dose
      effect curve. Chronic daily antalarmin treatment did not significantly decrease
      cocaine-maintained responding. Antalarmin did not significantly alter either the
      cocaine discrimination dose-effect curve or the time course of the cocaine
      training dose. Antalarmin (10 mg/kg) produced sedation, suggesting that it was
      centrally active, however, it did not attenuate cocaine's abuse-related effects
      in rhesus monkeys.

PMID- 17182091
TI  - Modeling the therapeutic efficacy of p53 restoration in tumors.
AB  - Although restoration of p53 function is an attractive tumor-specific therapeutic
      strategy, it remains unclear whether p53 loss is required only for transition
      through early bottlenecks in tumorigenesis or also for maintenance of established
      tumors. To explore the efficacy of p53 reinstatement as a tumor therapy, we used
      a reversibly switchable p53 knockin (KI) mouse model that permits modulation of
      p53 status from wild-type to knockout, at will. Using the well-characterized Emu
      myc lymphoma model, we show that p53 is spontaneously activated when restored in
      established Emu-myc lymphomas in vivo, triggering rapid apoptosis and conferring
      a significant increase in survival. Nonetheless, reimposition of p53 function
      potently selects for emergence of p53-resistant tumors through inactivation of
      p19(ARF) or p53. Our study provides important insights into the nature and timing
      of p53-activating signals in established tumors and how resistance to p53
      evolves, which will aid in the optimization of p53-based tumor therapies.

PMID- 17182092
TI  - Cryopreservation of tench, Tinca tinca, sperm: Sperm motility and hatching
      success of embryos.
AB  - The aim of the present study was to elaborate cryopreservation methods for ex
      situ conservation of tench. Success of cryopreservation was tested during two
      series of experiments. The first set of experiments studied the effects of two
      types of cryoprotectants (DMSO and a combination of DMSO with propanediol at
      ratio 1:1) at concentrations of 8 and 10% and three different equilibration times
      in two different immobilization solutions (IS) (Kurokura 180 and Kurokura) before
      freezing (0.0, 2.0 and 4.0h after T(0)). The K4 cooling programme was used to
      freeze 1ml of cryoextended sperm using 1.8ml cryotubes. Main monitored parameter
      was hatching rate after using of cryopreserved sperm. The second set of
      experiments studied the volume effect of 0.5, 1 and 5ml straws and compared these
      with 1.8ml cryotubes as well as the effect of the cooling programme (K4 and L1).
      Following the results of the first study, a combination of DMSO and propanediol
      (ratio 1:1) at concentration of 10% was added to extended sperm in Kurokura 180
      IS. Main monitored parameter was hatching rate after using cryopreserved sperm,
      supplementary parameters were sperm velocity and motility percentage assessed at
      10s post-activation. Sperm was collected directly into IS and stored at 4 degrees
      C for 2.5h. Thereafter were sperm samples pooled, equlibred in IS (first set of
      experiments) or directly mixed with cryoprotectants (DMSO or a mixture of DMSO
      with propanediol at ratio 1:1) and transferred to 1.8ml cryotubes or straws (0.5,
      1 and 5ml). Then the cryotubes/straws were directly transferred to pre-programmed
      PLANER Kryo 10 series III and cooled using two different cooling programmes
      including a slow cooling programme (a) named K4 (from +4 to -9 degrees C at a
      rate of 4 degrees Cmin(-1) and then from -9 to -80 degrees C at a rate of 11
      degrees Cmin(-1)) and a rapid cooling programme (b) named L1 (directly from +4 to
      -80 degrees C at a rate of 20 degrees Cmin(-1)). Both slow (K4) and rapid (L1)
      cooled samples were held 6min at -80 degrees C. Finally, samples were transferred
      into liquid N(2). The frozen spermatozoa were thawed in a water bath (40 degrees
      C) according to the frozen volume and checked for fertilization and hatching
      rates. Percentage of sperm motility and sperm velocity were measured using video
      recorded frames. ANOVA showed a significant influence of frozen and fresh sperm
      in all treatments. The hatching rates of 33.8% were obtained when sperm was
      equilibrated for 0h before freezing in IS of Kurokura 180 and frozen with a 10%
      of mixture 1:1 of DMSO and propanediol into straws of 5ml and cooled using
      program L1. The velocity of frozen-thawed spermatozoa ranged from 31 to
      46microms(-1) and in post-thawed sperm was not significantly different according
      to frozen sperm volume, but a higher velocity was obtained when sperm was fast
      frozen using programme L1. A large volume of frozen sperm could reveal the best
      procedure for freezing, but also for simulating methods of artificial propagation
      for future practical use of frozen tench sperm at a large scale.

PMID- 17182093
TI  - The effect of resin matrix composition on the polymerization shrinkage and
      rheological properties of experimental dental composites.
AB  - OBJECTIVES: This study was undertaken to evaluate the effect of the resin matrix
      composition of experimental composites on their polymerization shrinkage and
      rheological properties. METHODS: Six experimental composites consisting of
      varying ratios of Bis-GMA, TEGDMA, and UDMA were made. All composites had the
      same amount of filler (barium-aluminum-silicate glass, 76.5 wt.%) and initiator
      concentrations (camphorquinone, 1.7 wt.%). To investigate the effects of
      different resin matrices on the polymerization shrinkage, a newly developed
      measurement method was used. Using a rotational rheometer, a dynamic oscillatory
      shear test was undertaken to evaluate the rheological properties, including the
      storage shear modulus (G'), loss shear modulus (G''), loss tangent (tandelta),
      phase angle (delta), and complex viscosity (eta*) of the experimental composites
      as a function of frequency (0.1-10Hz). RESULTS: The polymerization shrinkage and
      complex viscosity of the experimental composites ranged from 2.61 to 3.88 vol.%
      and from 3.8 to 181.4Pas, respectively. The experimental composite composed of
      17.5% Bis-GMA and 4.4% TEGDMA showed the lowest shrinkage and highest viscosity.
      The composite composed of 8.7% Bis-GMA and 13.1% TEGDMA showed the highest
      shrinkage and lowest viscosity. With increasing TEGDMA content, the
      polymerization shrinkage increased but the viscosity decreased. The substitution
      of UDMA for TEGDMA reduced the shrinkage level but increased viscosity. There was
      an inverse relationship between the polymerization shrinkage and complex
      viscosity. All experimental composites exhibited pseudoplasticity. SIGNIFICANCE:
      Within the limitations of this study, resin matrix composition significantly
      affected the volumetric shrinkage and rheological properties of the experimental
      composites.

PMID- 17182094
TI  - Morphological regulation of rabbit chondrocytes on glucose-displayed surface.
AB  - A culture surface was designed to regulate morphology of rabbit chondrocytes by
      changing the ratio of D- and L-glucose isomers displayed on a glass plate. With
      increasing ratio of d-glucose displayed on the surfaces, the efficiency of cell
      attachment improved, meaning that the attachment exclusively occurred via
      mediation of an affinity between D-glucose displayed and glucose transporter on
      cell membrane. At 0% and 100% D-glucose display, the round-shaped cells appeared
      dominantly, and most of cells became stretched in shape at 50% d-glucose display,
      indicating that the frequency of round-shaped cells depicted a concave profile
      against the ratio of D-glucose displayed. From the cytoskeletal staining of F
      actin and vinculin, the immature stress fibers with fewer focal contacts were
      recognized in both the round shaped cells and those stretched in shape on 100% D
      glucose-displayed surface. The time-lapse observation revealed that the cells on
      100% D-glucose-displayed surface conducted active migration and aggregation with
      formation of collagen type II. These results suggest that 100% D-glucose
      displayed surface can offer culture environment to maintain the chondrocytic
      phenotype of cells, similarly to the conditions achieved in three-dimensional (3
      D) culture.

PMID- 17182095
TI  - Targeted and intracellular delivery of paclitaxel using multi-functional
      polymeric micelles.
AB  - Natural paclitaxel (Taxol) is an effective anti-cancer drug, although a critical
      disadvantage is its non-targeting nature. To address this issue, cholesterol
      grafted poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-co-undecenoic acid)
      was synthesized with different starting monomer ratios via a free radical
      copolymerization route. Folate was subsequently attached to the hydrophilic
      segment of the polymer in order to target folate receptors-overexpressing cancer
      cells. The success of synthesis was confirmed with 1H-NMR carried out in
      CDCl3/D2O. Using a membrane dialysis method, the polymer was then self-assembled
      into micelles whose hydrophobic cores could be utilized to encapsulate
      paclitaxel, an extremely hydrophobic compound. The polymer had a low CMC of
      approximately 20 mg/L in water. Dynamic light scattering further showed that the
      sizes of blank micelles formed from the polymer were below 180 nm at different pH
      values tested and approximately 220 nm upon drug incorporation. More importantly,
      it was demonstrated that the micelles exhibited a useful pH-induced thermo
      sensitivity, such that drug was released more rapidly at pH 5.0 (acidic
      endosomal/lysosomal environment) than at pH 7.4 (normal extracellular pH). In
      vitro cytotoxicity assays performed against KB cells then provided concluding
      evidences that the cellular uptake of micelles surface-functionalised with folate
      was indeed enhanced due to a receptor-assisted endocytosis process. This novel
      polymeric design thus has the potential to be a useful paclitaxel vehicle for the
      treatment of folate-receptor positive cancers.

PMID- 17182096
TI  - Analysis of ectopic and orthotopic bone formation in cell-based tissue-engineered
      constructs in goats.
AB  - Despite decades of extensive research, the application of cell-based bone tissue
      engineering in clinically relevant models remains challenging. To improve
      effectiveness, a better understanding of how the technique should work is
      crucial. In the current study, we investigated the onset time, rate, location and
      direction of bone formation in ectopically and orthotopically implanted
      clinically sized tissue-engineered constructs to gain insight the mechanism
      behind it. Bone marrow stromal cells (BMSCs) were obtained from 10 goats, culture
      expanded and cryopreserved. Porous biphasic calcium phosphate (BCP) disks of
      17mmx6mm were per-operatively seeded with BMSCs or left empty. Both conditions
      were implanted intramuscularly and in bilateral critical-sized iliac wing
      defects. Fluorochromes were administered at 3, 5 and 7 weeks and samples were
      retrieved after 9 weeks. Histology showed abundant and homogeneous bone formation
      throughout the intramuscular BMSC samples and little bone in the controls.
      Histomorphometry and measurements of the fluorochrome labels of the ectopical
      BMSC samples indicated that osteogenesis started at the periphery and subsequent
      osteoconduction filled the whole scaffold within 7 weeks. In the orthotopically
      implanted disks, there was good integration with the surrounding bone, but
      minimal bone in the center of the implants, in both conditions. Bone was only
      derived from the interface with the surrounding bone, there was no early bone at
      the surfaces in contact to soft tissue as was seen in the ectopical samples.
      Apparently cell survival was minimal and insufficient for relevant additional
      bone formation. However, the speed of integration with surrounding bone and
      subsequent bone apposition on the BMSC-seeded orthotopic scaffolds were found to
      be significantly enhanced, which may be relevant especially in challenging
      environments.

PMID- 17182097
TI  - Group analysis of regulation of fibroblast genome on low-adhesion nanostructures.
AB  - Nanotopographical material modification represents a possible way of producing
      surfaces that influence cellular adhesion for biomaterials purposes. Here, two
      low-adhesion surfaces are studied with human genome microarrays (120nm diameter
      pits produced by electron beam lithography and 11nm high columns produced by
      colloidal lithography). In order to present the large numbers of results produced
      in a succinct and easy to understand manner, two types of recent bioinformatics
      methods were used; iterative group analysis and Ingenuity pathway analysis. These
      methods allowed the easy comparison of the nanomaterials and showed large-scale
      changes in areas of extracellular matrix, cell signalling and inflammation. The
      results demonstrate that whilst modes of cellular response to low-adhesion
      materials are similar, the more adhesion is reduced, the further 'shut-down' of
      critical cellular activities is observed. We also feel that the analysis used
      could be of interest to biomaterials scientists looking for easy ways to display
      microarray data efficiently.

PMID- 17182098
TI  - Proteome analysis of human placentae: pre-eclampsia versus normal pregnancy.
AB  - Although placental proteins play multiple roles in fetal and placental
      development and in the maintenance of pregnancy, many remain inadequately
      characterized. In the present study, we comprehensively analyzed these proteins
      by using a proteomic approach. Samples were denatured with guanidine
      hydrochloride, which was found to be superior to the commonly used urea for the
      present purpose, and subjected to 2-dimensional (2D) electrophoresis (2-DE) to
      obtain placental proteome maps. The identified protein spots (ca. 60% of the
      total) on the proteome maps included several pregnancy-related proteins (PRPs).
      Furthermore, a novel 2D immunoblotting (2-DI) analysis of molecules related to
      pre-eclampsia revealed three immunopositive spots that appeared to correspond to
      dynactin p-50, a protein related to cell turn-over. The rate of positivity for
      dynactin p-50-reactive antibodies was significantly (P=0.0024) higher in 26 pre
      eclamptic women than in 58 normally pregnant women. These results indicate that
      dynactin p-50 may be involved in the pathophysiology of pre-eclampsia.

PMID- 17182099
TI  - Susceptibility to vertical transmission of Toxoplasma gondii is temporally
      dependent on the preconceptional infection in Calomys callosus.
AB  - Toxoplasma gondii is an obligate intracellular parasite that causes a variety of
      clinical syndromes, but the infection is more severe in immunocompromised
      individuals and in cases of congenital toxoplasmosis. This study aimed to verify
      if the susceptibility to vertical transmission of Toxoplasma gondii is temporally
      dependent on the preconceptional infection in Calomys callosus. Twelve C.
      callosus females were infected with 20 cysts of T. gondii ME49 strain and divided
      into three groups of four animals that were mated after approximately 10 days
      (group 1), 30 days (group 2), and 50 days (group 3) of infection. The animals
      were sacrificed from the 17th to 20th day of pregnancy, when placentas and
      embryos were collected for morphological and immunohistochemical studies, mouse
      bioassay for evaluating seroconversion and PCR for detecting parasite DNA. Serum
      samples from C. callosus females and mice used in bioassay were analysed for the
      detection of IgG antibodies to T. gondii by ELISA. Detection of T. gondii was
      observed by mouse bioassay and PCR in placentas and embryos from C. callosus
      females infected around 10 days pre-conception. However, only placentas, but not
      embryos, from females infected around 30 and 50 days pre-conception showed
      positivity for parasite DNA and seroconversion by mouse bioassay. In conclusion,
      this study model shows that vertical transmission of T. gondii may take place
      when maternal infection occurs within one month before conception, thus
      demonstrating the time of preconceptional seroconversion that rule out a risk of
      congenital toxoplasmosis.

PMID- 17182100
TI  - Contributions of the lipopolysaccharide outer core oligosaccharide region on the
      cell surface properties of Pseudomonas aeruginosa.
AB  - We have characterized the cell surface properties of three mutant series of
      Pseudomonas aeruginosa that show various defects in their lipopolysaccharide
      (LPS) core region. The deepest rough mutants of each series used in this study
      lacked completely rhamnose and glucose, and contained only galactosamine and
      alanine as LPS outer core constituents. However, rough mutants other than the
      deepest rough mutants showed high cell surface hydrophobicity compared to the
      corresponding parental strains, the deepest rough mutants showed less
      hydrophobicity than other rough mutants. The reactivity of an anti-lipid A
      monoclonal antibody with the deepest rough mutants was markedly higher than that
      with other counterparts. The deepest rough mutants tended to be more susceptible
      to antibiotics, such as gentamicin and polymyxin B, than the corresponding
      parental strains and other rough mutants. The above evidence indicates that
      neutral sugar, namely rhamnose and glucose, residues of the LPS outer core region
      play a critical role in the cell surface properties of P. aeruginosa.

PMID- 17182101
TI  - Evolutionary background for stress-coping styles: relationships between
      physiological, behavioral, and cognitive traits in non-mammalian vertebrates.
AB  - Reactions to stress vary between individuals, and physiological and behavioral
      responses tend to be associated in distinct suites of correlated traits, often
      termed stress-coping styles. In mammals, individuals exhibiting divergent stress
      coping styles also appear to exhibit intrinsic differences in cognitive
      processing. A connection between physiology, behavior, and cognition was also
      recently demonstrated in strains of rainbow trout (Oncorhynchus mykiss) selected
      for consistently high or low cortisol responses to stress. The low-responsive
      (LR) strain display longer retention of a conditioned response, and tend to show
      proactive behaviors such as enhanced aggression, social dominance, and rapid
      resumption of feed intake after stress. Differences in brain monoamine
      neurochemistry have also been reported in these lines. In comparative studies,
      experiments with the lizard Anolis carolinensis reveal connections between
      monoaminergic activity in limbic structures, proactive behavior in novel
      environments, and the establishment of social status via agonistic behavior.
      Together these observations suggest that within-species diversity of
      physiological, behavioral and cognitive correlates of stress responsiveness is
      maintained by natural selection throughout the vertebrate sub-phylum.

PMID- 17182103
TI  - Long-term behavioral consequences of soman poisoning in mice.
AB  - We investigated the long-term (up to 90 days) consequences of soman intoxication
      in mice on weight, motor performances (grip strength, rotarod) and mnemonic
      cognitive processes (T-maze, Morris water maze test). First, a relative weight
      loss of 20%, measured 3 days after intoxication, was evidenced as a threshold
      beyond which neuropathological damage was observed in the hippocampus. Animals
      were then distributed into either low weight loss (LWL) or high weight loss (HWL)
      groups according to the relative 20% weight loss threshold. Compared to controls,
      both groups of poisoned mice quickly exhibited a decrease in their motor
      performance subsequent to an acute soman toxicity phase. Then, total motor
      recovery occurred for the LWL group. Comparatively, HWL mice showed only
      transient recovery prior to a second decrease phase due to soman-induced delayed
      toxicity. One month after intoxication, mnemonic cognitive performances of the
      LWL group were similar to controls while the HWL group did not exhibit any
      learning skill. Three months after poisoning, compared to controls, the LWL group
      showed similar mnemonic performances in the maze test but a mild deficit in the
      Morris water maze task. At the same time, learning skills slightly recovered in
      the HWL group. Mnemonic cognitive data are discussed in relation to the
      neuropathology, neurogenesis and sprouting occurring in the hippocampus of soman
      intoxicated animals.

PMID- 17182104
TI  - The effects of physical activity in the acute treatment of bipolar disorder: a
      pilot study.
AB  - BACKGROUND: Physical activity has demonstrated efficacy in depression and
      anxiety, but its potential in the management of bipolar disorder is yet
      unexplored. This study is a pilot investigation into the effectiveness of an
      adjunctive walking program in the acute treatment of bipolar disorder. METHODS:
      This is a retrospective cohort study of all patients admitted over a 24-month
      period to a private psychiatric unit with a primary diagnosis of bipolar disorder
      (ICD-10). All patients were invited to participate voluntarily in a walking group
      during their admissions. Those who reliably attended the walking group
      (participants) were compared against those who did not attend (non-participants),
      using the clinician-rated Clinical Global Impression Severity (CGI-S) and
      Improvement (CGI-I) scales and the self-reported 21-item Depression Anxiety
      Stress Scales (DASS) as primary outcome measures. RESULTS: There were 24
      admissions for participants and 74 admissions for non-participants. The two
      groups did not differ significantly in patient demographics or admission CGI and
      DASS measures, except for a lower DASS Stress subscore for participants
      (p=0.049). At discharge, the inter-group differences in CGI measures remained non
      significant, but participants had significantly lower scores than non
      participants for DASS (p=0.005) and all its subscales (Depression p=0.048,
      Anxiety p=0.002, Stress p=0.01). LIMITATIONS: Methodological limitations include
      a retrospective design, small sample size, lack of randomisation or control, and
      indirect measure of manic symptoms. CONCLUSIONS: The results of this trial
      provide preliminary support for a therapeutic role of physical activity in
      bipolar disorder, and warrant further investigation with randomised controlled
      trials.

PMID- 17182105
TI  - Work stress, mental health and antidepressant medication findings from the Health
      2000 Study.
AB  - BACKGROUND: Population-based studies on the association between work stress and
      mental disorders are scarce, and it is not known whether work stress predicts
      mental disorders requiring treatment. AIMS: To examine the associations of work
      stress with DSM-IV mental disorders and subsequent antidepressant medication.
      METHODS: 3366 participants from a representative sample of the Finnish working
      population responded to a survey (The Health 2000 Study). 12-month prevalence of
      depressive or anxiety disorders was examined with the Composite International
      Diagnostic Interview. Data on antidepressant prescriptions with a 3-year follow
      up period were collected from a nationwide register of Social Insurance
      Institution. RESULTS: In men and women, high job demands, low job control and
      high job strain were associated with 12-month prevalence of depressive or anxiety
      disorders. After adjustment for lifetime and baseline mental disorders, men with
      high job demands and high job strain had increased risk of future antidepressant
      medication. CONCLUSIONS: Work stress is associated with mental disorders among
      both sexes and among men it is a risk factor for mental disorders treated with
      antidepressant medication.

PMID- 17182106
TI  - Plasma testosterone and dehydroepiandrosterone sulfate in male and female
      patients with dysthymic disorder.
AB  - BACKGROUND: Depressive symptomatology has been connected with an activation of
      the hypothalamus-pituitary-adrenal axis and, in several studies, with reduced
      androgen levels, while administration of androgens, usually in older subjects,
      may have positive effects on mood, both in males and females. Regarding dysthymic
      disorder (DD), low serum testosterone levels have been reported in older males,
      while information on younger male or on female patients is lacking. METHODS: We
      assessed the serum levels of testosterone (T), dehydroepiandrosterone sulfate
      (DHEAS) and cortisol in male and female patients with DD, and compared them to
      the levels of sex and age matched controls. Eighteen male and 43 female patients
      in the age range of 22 to 71 years were studied and diagnosed according to the
      Scheduled Diagnostic Interview for DSM-IV axis I disorders (SCID). Depressive
      symptomatology was assessed using the Hamilton Depression Rating Scale. Subgroups
      with subjects below or over 50 years of age were also built and compared.
      RESULTS: Serum T levels were lower than controls mainly in the subjects aged
      below 50 years, in both genders. More pronounced were reductions in DHEAS levels
      both in male and female patients, while cortisol levels were normal or reduced. T
      levels were positively correlated to both DHEAS and cortisol. The negative
      correlations of DHEAS and T to age were significant for all groups and subgroups,
      except in the group of male patients. Four male patients (22%) had T levels below
      2.0 ng/ml. CONCLUSIONS: Male and female patients with DD aged below 50 years show
      reduced gonadal and adrenal androgen levels, and normal to low cortisol levels.
      These neuroendocrine characteristics differentiate DD from depression, and place
      this diagnostic group closer to posttraumatic stress disorder.

PMID- 17182102
TI  - 17Beta-estradiol downregulates Kupffer cell TLR4-dependent p38 MAPK pathway and
      normalizes inflammatory cytokine production following trauma-hemorrhage.
AB  - Although studies have shown that 17beta-estradiol (estradiol) normalized Kupffer
      cell function following trauma-hemorrhage, the mechanism by which E2 maintains
      immune function remains unclear. Activation of Toll-like receptor 4 (TLR4)
      initiates an inflammatory cascade, involving activation of p38 mitogen-activated
      protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and nuclear factor
      kappaB (NF-kappaB). This leads to the release of proinflammatory cytokines. Thus,
      we hypothesized that the salutary effects of estradiol on Kupffer cell function
      following trauma-hemorrhage are mediated via negative regulation of TLR4
      dependent p38 MAPK and NF-kappaB. TLR4 mutant (C3H/HeJ) and wild type (C3H/HeOuJ)
      mice were subjected to trauma-hemorrhage (mean BP 35+/-5 mmHg approximately 90
      min, then resuscitation) or sham operation. Administration of estradiol following
      trauma-hemorrhage in wild type mice decreased Kupffer cell TLR4 expression as
      well as prevented the phosphorylation of p38 MAPK and NF-kappaB. This was
      accompanied by normalization of Kupffer cell production capacities of IL-6, TNF
      alpha, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 and the decrease
      in plasma cytokine levels. In contrast, TLR4 mutant mice did not exhibit the
      increase in Kupffer cell p38 MAPK and NF-kappaB activation, cytokine production,
      or the increase in circulating cytokine levels following trauma-hemorrhage. No
      difference was observed in activation of PI3K among groups. These results suggest
      that the protective effect of estradiol on Kupffer cell function is mediated via
      downregulation of TLR4-dependent p38 MAPK and NF-kappaB signaling following
      trauma-hemorrhage, which prevents the systemic release of cytokines.

PMID- 17182107
TI  - Suicide in adolescents: using life charts to understand the suicidal process.
AB  - BACKGROUND: A greater understanding of the pathways which lead young people to
      take their lives is important in ensuring that prevention strategies and health
      service delivery are as effective as possible. In this study we examined the
      duration, development and characteristics of the suicidal process in young people
      who ultimately died by suicide. METHODS: Life charts of psychological autopsy
      information from multiple informants were used to identify the suicidal process
      among 27 young people who died by suicide. RESULTS: Life charts were generated
      for 27 young people who died by suicide, of whom 93% (n=25) were male, with an
      average age at death of 20.9 years (SD=2.4). Three types of suicidal process were
      identified: Group I characterised by longstanding difficulties which spanned the
      developmental domains of home, school and peers. The suicidal process was
      longstanding, and included deliberate self-harm prior to their death and direct
      communication to friends and family about suicidal ideas and plans. The second
      group was characterised by evidence of an established psychiatric disorder. Two
      subgroups were identified, namely those individuals with a protracted suicidal
      process which lasted approximately 5-9 years, and those with a brief suicidal
      process lasting approximately one year. The third and smallest group was
      characterised by the emergence of the suicidal process as an acute response to
      life events among young people who appeared to have previously been functioning
      well, without apparent mental illness or known self-harm. However, two out of
      five in this group communicated specific suicidal intent in the weeks before
      their death. CONCLUSIONS: The suicidal process may emerge and disappear in the
      lives of young people. Repeated episodes of self-cutting by young men, against a
      backdrop of substance abuse, relationship difficulties, and mental health
      problems require further clinical attention.

PMID- 17182109
TI  - Toll-like receptor 2 ligand mediates the upregulation of angiogenic factor,
      vascular endothelial growth factor and interleukin-8/CXCL8 in human rheumatoid
      synovial fibroblasts.
AB  - Rheumatoid arthritis (RA) is characterized by infiltrations of inflammatory cells
      accompanied by neovascularization in the joint. We hypothesized that cell
      activation via the toll-like receptor (TLR) may be involved in the induction of
      angiogenic molecules, which are relevant to the pathogenesis of RA. RA fibroblast
      like synoviocytes (FLS) were stimulated with TLR-2 ligand bacterial peptidoglycan
      (PGN), TLR-4 ligand lipopolysaccharide (LPS) and various cytokines. Vascular
      endothelial growth factor (VEGF) and IL-8 were measured by ELISA in culture
      supernatants; mRNA levels were assessed by RT-PCR and real time PCR. The levels
      of TLR-2, VEGF and IL-8 were analyzed by dual immunohistochemistry in RA synovium
      and compared with osteoarthritis (OA). Regulation of MyD88, IRAK4, IRAK1, IRAK-M
      and TRAF-6 mRNA expression levels by PGN were analyzed by RT-PCR. Phosphorylation
      of I kappa B alpha was evaluated by western blotting. Levels of VEGF and IL-8
      were upregulated in culture supernatants of RA FLS stimulated with PGN, similar
      to the levels of IL-1beta and IL-17 stimulation. Neutralization of TLR-2 with a
      blocking monoclonal antibody significantly reduced both VEGF and IL-8 levels
      (P<0.05), which reflected the functional relevance of TLR-2 activation to the
      induction of VEGF and IL-8 production. Downstream intracellular signaling
      following TLR-2 stimulation involved MyD88-IRAK-4-TRAF-6 pathways, resulting in
      NF-kappaB activation. Thus, TLR-2 activation in RA FLS by microbial constituents
      could be involved in the induction of VEGF and IL-8 and thereby promote
      inflammation either directly or via angiogenesis. This possibly contributes to
      the perpetuation of synovitis in patients with RA.

PMID- 17182111
TI  - An EMG screening method (dysphagia limit) for evaluation of neurogenic dysphagia
      in childhood above 5 years old.
AB  - Oropharyngeal dysphagia is not rare in older children before the adult age,
      especially the patients with cerebral palsy. Non-invasive simple tests are needed
      for the evaluation of children with neurogenic dysphagia including the patients
      with cerebral palsy. So we aimed to evaluate non-invasive ways to screen for
      dysphagia in children and the usefulness of this almost new electrophysiologic
      method for the detection of dysphagia in children with cerebral palsy. Twenty
      eight healthy children and 12 patients with cerebral palsy were investigated for
      the applicability of this method. The movement of the larynx was monitored using
      a simple piezoelectric wafer sensor and submental surface EMG activity was
      recorded by bipolar silver-chloride electrodes taped under the chin over the
      submental muscle complex. The onset and duration of pharyngeal swallowing was
      recorded from submental-suprahyoid muscles such as the mylohyoid-genitohyoid
      anterior digastric complex. By this method, the maximal water volume capacity was
      measured in single swallows with progressively increasing water volumes, this was
      called 'dysphagia limit'. The healthy control children revealed to swallow the
      bolus at once maximally 11.2+/-0.4 and 2.5 ml in average. Dysphagia limit varied
      from 7 to above 20 ml water volume from age 5-16 years old. Patients with
      cerebral palsy had the dysphagia limit of 7.7+/-1.8 and 6.4 ml in average. The
      dysphagia limit was significantly reduced in patients with cerebral palsy
      (p<0.05). Dysphagia limit seemed to be less sensitive in demonstrating the
      oropharyngeal swallowing disorders in childhood period (90% in the adult
      dysphagic patients). But the majority of patients with cerebral palsy (58%)
      showed abnormality. This electrophysiologic method is completely non-invasive,
      devoid from any hazard and applicable to children above 5 years. It may be
      candidate as a screening test before selection of dysphagic children.

PMID- 17182110
TI  - PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of
      experimental autoimmune encephalomyelitis.
AB  - Interactions between PD-1 and its two differentially expressed ligands, PD-L1 and
      PD-L2, attenuate T cell activation and effector function. To determine the role
      of these molecules in autoimmune disease of the CNS, PD-1-/-, PD-L1-/- and PD-L2
      /- mice were generated and immunized to induce experimental autoimmune
      encephalomyelitis (EAE). PD-1-/- and PD-L1-/- mice developed more severe EAE than
      wild type and PD-L2-/- mice. Consistent with this, PD-1-/- and PD-L1-/- cells
      produced elevated levels of the pro-inflammatory cytokines IFN-gamma, TNF, IL-6
      and IL-17. These results demonstrate that interactions between PD-1/PD-L1, but
      not PD-1/PDL-2, are crucial in attenuating T cell responses in EAE.

PMID- 17182108
TI  - Effects of antidepressant treatment on neural correlates of emotional and neutral
      declarative verbal memory in depression.
AB  - BACKGROUND: Multiple studies have documented deficits in verbal declarative
      memory function in depression that improve with resolution of symptoms; imaging
      studies show deficits in anterior cingulate function in depression, a brain area
      that mediates memory. No studies to date have examined neural correlates of
      emotionally valenced declarative memory using affectively negative (sad) verbal
      material that is clinically relevant to understanding depression. Also no studies
      have examined the effects of treatment on neural correlates of verbal declarative
      memory. The purpose of this study was to examine the effects of treatment with
      antidepressants on verbal declarative memory in patients with depression.
      METHODS: Subjects with (N=18) and without (N=9) mid-life major depression
      underwent positron emission tomography (PET) imaging during verbal declarative
      memory tasks with both neutral paragraph encoding compared to a control
      condition, and emotional (sad) word pair retrieval compared to a control
      condition. Imaging was repeated in 13 subjects with depression after treatment
      with antidepressants. RESULTS: Patients with untreated depression had a failure
      of anterior cingulate activation relative to controls during retrieval of
      emotional word pairs. Antidepressant treatment resulted in increased anterior
      cingulate function compared to the untreated baseline for both neutral and
      emotional declarative memory. LIMITATIONS: Limitations include a small sample
      size and variety of antidepressants used. CONCLUSIONS: These results are
      consistent with alterations in anterior cingulate function that are reversible
      with treatment in patients with depression. These findings may have implications
      for understanding the mechanism of action of antidepressants in the treatment of
      depression.

PMID- 17182112
TI  - Generation of a transposon insertion mutant library for bovine herpesvirus 4
      cloned as a bacterial artificial chromosome by in vitro MuA based DNA
      transposition system.
AB  - Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus with no clear disease
      association. Although the BoHV-4 genome has been sequenced, the function of the
      majority of putative genes is elusive. Several features make BoHV-4 attractive as
      a backbone for use as a viral expression vector and/or as a model to study gamma
      herpesvirus biology and determining which genes are essential for its replication
      is a very important task. Starting from BoHV-4 genome cloned as infectious
      bacterial artificial chromosome (BAC-BoHV-4) in Escherichia coli. A random
      insertion mutant library for BoHV4 was generated by the use of MuA transposase
      catalyzed in vitro transposition reaction. Viral mutant transfection and direct
      sequencing allow the rapid determination of which BoHV-4 genes are essential for
      viral growth in a permissive eukaryotic cell line. BoHV-4 functional analysis
      information is fundamental when the BoHV-4 genome is modified for vector
      purposes.

PMID- 17182113
TI  - Differentiation of Potato virus Y strains using improved sets of diagnostic PCR
      primers.
AB  - Potato virus Y (PVY) is one of the most important viruses of potato world-wide,
      several strain groups are recognized. In the past two decades, novel PVY variants
      have appeared causing necrotic symptoms on potato tubers. Implicated are two
      groups of recombinant strains: PVY(N)W and PVY(NTN), and NA-PVY(NTN). While the
      first two are recombinants between PVY-N- and O-strains the latter is a
      recombinant between an N-strain and an unknown PVY strain or other Potyvirus.
      Available biological and molecular data on PVY suggest that classification of PVY
      strains has to be revised. Some drawbacks have been found with recently published
      primers used in RT-PCR based differentiation of PVY strains as some defined
      isolates could not be identified correctly. Consequently we developed new primers
      using both recently available sequences and newly generated complete sequences of
      PVY strains. The reliability of these newly developed primers and procedures was
      successfully demonstrated on nearly 100 biologically and serologically
      characterised PVY isolates.

PMID- 17182114
TI  - Deficient prepulse inhibition induced by selective breeding of rats can be
      restored by the dopamine D2 antagonist haloperidol.
AB  - Deficient sensorimotor gating, measured as prepulse inhibition (PPI) of startle,
      reflects disturbed information processing found in neuropsychiatric disorders.
      Examining the ability to selectively breed rats for high and low PPI, results
      showed significant differences of PPI scores within two generations. Comparing
      antipsychotics to restore PPI of the low group, haloperidol was shown more
      effective than clozapine. This suggests low PPI rats may be useful models for
      neuropsychiatric disorders and screening antipsychotics.

PMID- 17182115
TI  - Sequential bilateral striatal lesions have additive effects on single skilled
      limb use in rats.
AB  - Unilateral dopamine depletion in rats induced by injection of 6-hydroxydopamine
      (6-OHDA) into the nigrostriatal system causes permanent impairments in limb use.
      The disturbances in limb use, including impairments in skilled reaching, are most
      severe on the side contralateral to the lesion. A number of studies, however,
      have also described ipsilateral deficits in skilled reaching. The purpose of this
      study was to investigate the effects of sequential bilateral striatal 6-OHDA
      lesions on skilled reaching movements in rats to compare the contribution of
      contra- versus ipsilateral motor control. Rats were trained in a reaching task to
      grasp food pellets with their preferred paw prior to receiving an intrastriatal 6
      OHDA injection on the side contralateral to the preferred paw. The lesion
      significantly reduced reaching success along with qualitative impairments in limb
      use. In addition, animals displayed asymmetry in limb use and contraversive
      rotation bias after an apomorphine challenge. Three weeks later, animals received
      a second lesion induced by intrastriatal 6-OHDA injection into the hemisphere
      ipsilateral to the preferred paw. This lesion exaggerated the previous
      impairments in limb use and further reduced reaching success of the preferred
      paw. In the ladder rung walking task, additional impairments were found only in
      the forelimb ipsilateral to the first lesion. The findings of additive effects of
      sequential bilateral lesions suggest that both the contra- and ipsilateral
      striatum control single limb use. This supports the notion of bilateral control
      of skilled forelimb use by the mesostriatal dopaminergic system.

PMID- 17182116
TI  - Transient drug-primed but persistent cue-induced reinstatement of extinguished
      methamphetamine-seeking behavior in mice.
AB  - It is essential to develop animal models to study the role of genetic factors in
      the relapse of drug-seeking behavior in genetically engineered mutant mice. This
      paper reports a typical model of drug-primed and cue-induced reinstatement of
      extinguished methamphetamine (METH)-seeking behavior in mice. C57BL/6J mice were
      trained to self-administer METH (0.1mg/kg/infusion) by poking their nose into an
      active hole under a fixed ratio schedule in daily 3-h sessions. After acquiring
      stable METH self-administration behavior, the mice were subjected to extinction
      training in the absence of both METH and METH-associated cues. Once the active
      nose-poking responses were extinguished, drug-primed and cue-induced
      reinstatement were investigated according to a within-subjects design. A priming
      injection of METH reliably reinstated the extinguished drug-seeking behavior in
      the absence of both METH and METH-associated cues. Interestingly, the drug-primed
      METH-seeking behavior disappeared within 2 months after withdrawal from METH,
      while cue-induced reinstatement of extinguished METH-seeking behavior lasted for
      at least 5 months after the withdrawal. A correlation study revealed that drug
      primed, but not cue-induced, reinstatement behavior was positively correlated
      with the total amount of METH taken by individuals during METH self
      administration. In conclusion, our findings suggest that the present
      reinstatement procedure for mouse model of relapse is useful and reliable, and
      different neural mechanisms may be involved in drug-primed and cue-induced METH
      seeking behavior.

PMID- 17182117
TI  - Effect of precocious locomotor activity on the development of motoneurones and
      motor units of slow and fast muscles in rat.
AB  - We have investigated the effect of precociously increasing locomotor activity
      during early postnatal development by daily treatment with the monoaminergic
      precursor L-DOPA on the survival of motoneurones supplying the slow soleus (SOL)
      muscle and the fast, tibialis anterior (TA) and extensor digitorum longus (EDL)
      muscles as well as the contractile and histochemical properties of these muscles.
      L-DOPA treatment resulted in a significant loss of motoneurones to the slow SOL
      muscle, but not to the fast TA and EDL muscles. Moreover, motoneurones to fast
      muscles also die as when exposed to increased activity in early life, if their
      axons are repeatedly injured. The loss of normal soleus motoneurones was
      accompanied by an increase in force of the remaining motor units and sprouting of
      the surviving axons suggesting a remodelling of motor unit organisation. The time
      to peak contraction of both SOL and EDL muscles from L-DOPA treated rats was
      prolonged at 8 weeks of age. At 4 weeks the soleus muscles of the L-DOPA treated
      animal developed more tension than the saline treated one. This difference
      between the two groups did not persist and by 8 weeks of age the muscle weight
      and tetanic tension from either group were not significantly different from
      control animals. The present study shows that early transient, precocious
      locomotor activity induced by L-DOPA is damaging to normal soleus but not to
      normal EDL/TA motoneurones.

PMID- 17182118
TI  - Facilitatory effect of the intra-hippocampal pre-test administration of MT3 in
      the inhibitory avoidance task.
AB  - The cholinergic system plays a crucial role in learning and memory. Modulatory
      mechanisms of this system in the acquisition and consolidation processes have
      been extensively studied, but their participation in the memory retrieval process
      is still poorly understood. Conventional pharmacological agents are not highly
      selective for particular muscarinic acetylcholine receptor subtypes. Muscarinic
      toxins (MTs) that are highly selective for muscarinic receptors were extracted
      from the venom of the mamba snake, like the toxin MT3, selective for the M4
      receptor subtype. These toxins are useful tools in studies of the specific
      functions of the M4 mediated transmission. The M4 receptor selective antagonist
      MT3, given into the dorsal hippocampus before the test, have enhanced the memory
      retrieval of an inhibitory avoidance task in rats. MT3 had no effect in the
      habituation to a new environment, including basic motor parameters, meaning that
      the effect in he inhibitory avoidance is purely cognitive. Our results suggest an
      endogenous negative modulation of the cholinergic muscarinic system upon the
      retrieval of previously consolidated aversive memories, hereby shown by the
      facilitatory effect of MT3.

PMID- 17182119
TI  - Long-term exposure to arsenic affects head kidney and impairs humoral immune
      responses of Clarias batrachus.
AB  - The present study was aimed at determining the effects of long-term arsenic
      exposure on the head kidney (HK) and ensuing humoral immune responses in Clarias
      batrachus L. Long-term exposure (150 days) to non-lethal concentrations of
      arsenic (42.42 microM) resulted in significant time-dependent alterations in HK
      cell number eventually affecting the HK somatic index. Prolonged exposure to
      arsenic also suppressed HK-B cell proliferation and led to significant reduction
      in serum immunoglobulin levels and antigen-specific serum bacterial agglutinin
      titers. A decline in the number of antigen-specific plaque-forming cells with
      duration of arsenic exposure was noted in the HK. Enzyme linked immunosorbent
      assays further revealed that arsenic exposure inhibited the release of "IL-4 like
      factors" from HK-T cells. Histological studies documented time-dependent changes
      in the structure and cellular composition of HK characterized by extensive
      lymphocytopenia, decrease in melano-macrophage population and hemosiderin
      accumulation. From exposure-challenge studies with Aeromonas hydrophila it was
      evident that pathogens could efficiently disseminate and colonize distant host
      tissues in the exposed fish. Moreover, the ability to decrease the pathogen load
      was also significantly reduced in the arsenic-exposed fish. Thus long-term
      exposure to non-lethal concentrations of arsenic affects HK and interferes with
      the humoral immune system of C. batrachus rendering them immunocompromised and
      susceptible to pathogenic challenge.

PMID- 17182120
TI  - Regulation of TFF3 expression by homeodomain protein CDX2.
AB  - Although trefoil factor family 3 (TFF3) plays an important role in protecting the
      intestinal mucosa, the regulatory mechanisms of its expression are not fully
      understood. Since homeodomain protein CDX2 has been reported to be critically
      involved in the development and differentiation of intestinal epithelium, we
      examined whether CDX2 affects the expression of TFF3. The transcription of human
      TFF3 reporter genes was significantly up-regulated by the transient
      overexpression of CDX2 in COS-7 cells and AGS gastric cells. Electrophoretic
      mobility shift assay revealed the presence of at least two CDX-binding sites
      within the human TFF3 promoter. Deletion analysis showed the relative importance
      of the proximal CDX-binding site at -63. We also detected the up-regulation of
      endogenous TFF3 mRNA expression in AGS cells stably transfected with CDX2
      expression vectors. These results suggest that CDX2 plays a key role in the
      expression of TFF3 in the intestine and perhaps in intestinal metaplasia of the
      stomach.

PMID- 17182121
TI  - The effects of saltwater acclimation on neurotransmitters in the lingual salt
      glands of the estuarine crocodile, Crocodylus porosus.
AB  - INTRODUCTION: Most avian and reptilian salt glands display marked phenotypic
      plasticity when animals are exposed to hyperosmotic conditions. In addition, the
      activity of most salt glands is under considerable control by the nervous system
      and nerves containing cholinergic, adrenergic and peptidergic neurotransmitters
      have been identified in avian and reptilian salt gland tissues. The present study
      sought to determine whether the salt glands of the estuarine crocodile,
      Crocodylus porosus contain the peptidergic neurotransmitters SP, CGRP, VIP, and
      PACAP and the gaseous neurotransmitter, NO. In addition, we sought to determine
      whether there was any evidence for the adaptation of the C. porosus salt gland
      nervous system to hyperosmotic conditions. METHODS: Salt glands from freshwater-
      and saltwater-acclimated C. porosus hatchlings were sectioned and examined
      immunohistochemically for neurotransmitters within the tissue. RESULTS: Neurons
      containing SP, CGRP, VIP, PACAP and NO synthase were identified within C. porosus
      salt glands. There was no difference in the overall number (density) of neurons
      within SW-acclimated tissues when compared with FW-acclimated animals. However,
      there was a significant reduction in density of neurons containing SP and PACAP
      in SW-acclimated animals. CONCLUSION: C. porosus salt glands display phenotypic
      plasticity following exposure to hyperosmotic conditions. In addition to
      cholinergic and adrenergic neurons, they contain a variety of peptidergic
      neurotransmitters and the gaseous neurotransmitter NO. Additionally, there
      appears to be some evidence of acclimation of the nervous system of C. porosus to
      hypersaline conditions, although the functional significance of these changes
      remains to be determined.

PMID- 17182122
TI  - Central CART gene delivery by recombinant AAV vector attenuates body weight gain
      in diet-induced-obese rats.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptide is a neuro-peptide
      implicated in the regulation of energy homeostasis. CART mRNA and its encoded
      peptide have been found in many brain regions that regulate energy balance. To
      investigate the effects of chronic central expression of CART in the diet-induced
      obese (DIO) rats, we constructed and packaged recombinant adeno-associated virus
      (AAV) 2 vector containing rat CART cDNA and a reporter gene encoding green
      fluorescence protein (AAV-rCART-hrGFP) driven by the CMV promoter. Approximately
      1x10(11) particles of AAV-rCART-hrGFP or control vector AAV-IRES-hrGFP (AAV-hrGFP
      in short) were injected through intracerebroventricular (ICV) cannulas into adult
      male DIO Long-Evans rats. Throughout the 7-month study period, AAV-rCART-hrGFP
      injected rats had a significantly decreased food intake and body weight gain when
      compared with those of AAV-hrGFP-injected rats. AAV-rCART-hrGFP injection also
      modulated hyperphagia following a 24-hour fasting in these rats. Body composition
      analysis indicated that decreased body weight gain was due to reduction in lean
      body mass while fat mass was not affected. Expression of green fluorescence
      protein (GFP) suggested that recombinant AAV virions are located at cells
      surrounding the third ventricle and medial eminence. Our results demonstrate that
      chronic expression of CART in brain can modulate energy intake in diet-induced
      obese rats. The CART pathway plays an important role in body mass regulation in
      DIO rats.

PMID- 17182124
TI  - Identification and characterization of genes associated with the induction of
      embryogenic competence in leaf-protoplast-derived alfalfa cells.
AB  - Alfalfa leaf protoplast-derived cells can develop into somatic embryos depending
      on the concentration of 2,4-dichlorophenoxyacetic acid (2,4-D) in the initial
      culture medium. In order to reveal gene expression changes during the
      establishment of embryogenic competence, we compared the cell types developed in
      the presence of 1 and 10 microM 2,4-D, respectively, at the time of their first
      cell divisions (fourth day of culture) using a PCR-based cDNA subtraction
      approach. Although the subtraction efficiency was relatively low, applying an
      additional differential screening step allowed the identification of 38 10 microM
      2,4-D up-regulated transcripts. The corresponding genes/proteins were annotated
      and representatives of various functional groups were selected for more detailed
      gene expression analysis. Real-time quantitative PCR (RT-QPCR) analysis was used
      to determine relative expression of the selected genes in 2,4-D-treated leaves as
      well as during the whole process of somatic embryogenesis. Gene expression
      patterns confirmed 2,4-D inducibility for all but one of the 11 investigated
      genes as well as for the positive control leafy cotyledon1 (MsLEC1) gene. The
      characterized genes exhibited differential expression patterns during the early
      induction phase and the late embryo differentiation phase of somatic
      embryogenesis. Genes coding for a GST-transferase, a PR10 pathogenesis-related
      protein, a cell division-related ribosomal (S3a) protein, an ARF-type small
      GTPase and the nucleosome assembly factor family SET protein exhibited higher
      relative expression not only during the induction of somatic embryogenesis but at
      the time of somatic embryo differentiation as well. This may indicate that the
      expression of these genes is associated with developmental transitions
      (differentiation as well as de-differentiation) during the process of somatic
      embryogenesis.

PMID- 17182125
TI  - Angiotensin converting enzyme insertion/deletion polymorphism in sporadic and
      familial Alzheimer's disease and longevity.
AB  - A recent, large meta-analysis has reproposed the role of the angiotensin
      converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a risk factor
      for Alzheimer's disease (AD). To further investigate the proposed association and
      to better clarify the role of ACE as a risk factor for AD, we analyzed the
      genotype and allele frequency distribution of ACE I/D and apolipoprotein E (APOE)
      gene polymorphisms in 235 Italian patients with sporadic AD, 153 with familial AD
      (FAD), 192 healthy controls and 111 centenarians. Patients with AD were
      consecutively gathered from among the outpatients from the Neurology Department
      at the University of Florence. All 691 subjects were genotyped for ACE and APOE
      polymorphisms. There were no significant differences in ACE genotypes or allele
      frequencies in all the studied groups, even after stratification for APOE
      epsilon4 carrier status. Centenarians show the highest allele D frequency,
      although the value is not significant, thus suggesting a possible implication of
      the D allele as an epistatic allele that has pleiotropic age-dependent effects.
      In conclusion, our data suggest that the ACE allelic variant is not a
      susceptibility factor in sporadic and familial AD (FAD), nor does it mitigate the
      effect of the APOE epsilon4 allele in the risk of developing AD. Moreover, our
      data do not suggest a possible involvement of the D allele in longevity.

PMID- 17182123
TI  - Regulation of Smad activities.
AB  - TGF-beta (Transforming Growth Factor-beta) cytokines employ Smad proteins as the
      intracellular mediator of signaling. Upon TGF-beta stimulation, the cytoplasmic
      Smads become phosphorylated and consequently accumulate in the nucleus to
      regulate target gene expression. The cytoplasm-to-nucleus redistribution of
      Smads, as well as the ability of Smads to activate or repress gene transcription,
      is under multiple layers of regulation by factors not limited to TGF-beta. With
      recent advance in the knowledge of regulatory factors impinged on Smads, we are
      beginning to understand the complexity in cellular responses to TGF-beta.

PMID- 17182126
TI  - Feasibility and safety of granulocyte colony-stimulating factor treatment in
      patients with acute myocardial infarction.
AB  - BACKGROUND: This study examined feasibility and safety of granulocyte colony
      stimulating factor (G-CSF) treatment for patients with acute myocardial
      infarction (AMI). METHODS: Forty patients with AMI related with the left anterior
      descending coronary artery, who underwent successful percutaneous coronary
      intervention (PCI), were randomized into G-CSF group (n=18) or Control group
      (n=22). G-CSF treatment was started within 24 h after PCI. 99mTc-tetrofosmin
      single-photon emission computed tomography (SPECT) was performed at 4 days and 6
      months after AMI. SPECT data was analyzed for LV end-diastolic volume (LVEDV), LV
      end-systolic volume (LVESV), LV ejection fraction (LVEF) and myocardial
      perfusion. RESULTS: LVEF at 6 months was significantly better than that at 4 days
      in G-CSF group (p=0.013), but not changed in Control group (p=0.245). Although no
      significant difference was observed for LVEDV between the two groups, LVESV
      tended to be decreased only in G-CSF group. In G-CSF group, defect score (DS) was
      significantly decreased from 4 days to 6 months after AMI. Restenosis rate at 6
      months after AMI was not significantly different between the two groups.
      CONCLUSIONS: G-CSF treatment for patients with AMI was effective and did not have
      any clinical and angiographic adverse effects.

PMID- 17182129
TI  - B-type natriuretic peptide kinetics and cardiopulmonary exercise testing in heart
      failure.
AB  - BACKGROUND: In patients with chronic heart failure (CHF), B-type natriuretic
      peptide (BNP) is related to peak oxygen consumption (peak VO2) and the
      relationship between minute ventilation and carbon dioxide production (VE/VCO2
      slope). However, the exercise response depends on the mode of exercise. This
      study sought to compare peak treadmill and bicycle exercise responses with
      respect to their relationship with BNP and to assess whether BNP measured at rest
      or during exercise could identify patients with greater functional impairment and
      ventilatory inefficiency. METHODS: Twenty-three patients with mild-to-moderate
      stable systolic CHF (age 72+/-8 years, left ventricular ejection fraction 32+/
      7%) underwent treadmill and bicycle cardiopulmonary exercise testing within 5
      (interquartile range 3-7) days. BNP was measured at rest and at peak exercise.
      RESULTS: BNP at rest was an independent multivariate predictor of both peak VO2
      and the VE/VCO2 slope for both exercise modes. However, the proportion of
      variance explained univariately and multivariately was < or = 0.55, indicating
      that BNP did not strongly explain the variation of peak VO2 and the VE/VCO2
      slope. The exercise-induced rise in circulating BNP did not differ between the
      test modes [treadmill: 50 (24-89) pg/ml vs. bicycle: 46 (15-100) pg/ml; p=0.73].
      BNP levels at peak exercise were strongly related to resting values, but did not
      provide additional information on peak VO2 or the VE/VCO2 slope. CONCLUSIONS: In
      typical CHF patients, BNP measured at rest or at peak exercise does not strongly
      predict peak VO2 or the VE/VCO2 slope regardless of the exercise mode, and is
      therefore not a sufficiently accurate surrogate for cardiopulmonary exercise
      testing.

PMID- 17182130
TI  - Sexual functioning and congenital heart disease: Something to worry about?
AB  - BACKGROUND: Although sexual problems in cardiac patients are receiving increasing
      attention, research on sexual functioning of patients with congenital heart
      disease is very scarce. Therefore, this study investigated sexual functioning in
      adults with congenital heart disease and compared this with that of matched,
      healthy control subjects. METHODS: A descriptive, comparative study was
      conducted, in which 441 adults with congenital heart disease were matched to 441
      healthy counterparts, according to age, gender, and marital status. The sample
      consisted of 53.5% males. Median age was 24 years. Disease-specific determinants
      of quality of life were assessed using the CHD-TAAQOL. This 77-item instrument
      includes five items referring to sexual problems. For each item, both the
      perceived frequency and the associated distress were scored. RESULTS: Sexual
      problems were perceived by 10% to 20% of the patients. When these problems
      occurred, they were distressing in 67% to 88% of the patients. Female patients
      reported significantly more often 'not enjoying having sex', 'being insecure
      about having sex', and 'not being aroused while having sex', and experienced more
      distress at 'being insecure about having sex' than male patients. Congenital
      heart disease patients reported significantly fewer 'not enjoying having sex' and
      'worrying about your sex life' than healthy counterparts, but experienced more
      distress at 'worrying about your sex life'. CONCLUSION: In this study, we found
      that only a minority of adults with congenital heart disease reported sexual
      problems. This suggests that sexual functioning in this group of patients is not
      as problematic as in some other cardiac populations.

PMID- 17182131
TI  - Neurohormonal activation and left ventricular ejection fraction in patients with
      suspected myocardial ischemia.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) and left ventricular ejection
      fraction (LVEF) are both increasingly used in the clinical management of patients
      with suspected coronary artery disease (CAD). Unfortunately, there is very
      limited data regarding the association between BNP and LVEF. METHODS: BNP and
      LVEF were measured in 260 consecutive patients with suspected myocardial ischemia
      referred for rest/ergometry myocardial perfusion single-photon emission computed
      tomography (SPECT). The correlation between BNP and LVEF was studied using
      Spearman's correlation test. RESULTS: Median LVEF was 57% (IQR, 50 to 64), and
      median BNP level was 53 pg/ml (IQR, 24 to 109). LVEF and BNP levels showed a
      statistically significant, but overall weak correlation (r=0.274, p<0.001). The
      correlation seemed to depend on the presence of a myocardial scar, which was
      detected in 104 patients (40%), including 89 men (49% of men) and 15 women (20%
      of women). The correlation between BNP and LVEF was moderate in patients with a
      myocardial scar (r=-0.540, p<0.001), but very weak in patients without a scar
      (r=0.185, p=0.025). Moreover, the correlation between BNP and LVEF was moderate
      in men (r=-0.503, p<0.001), but not existent at all in women. In the overall
      cohort, BNP was not an accurate test to detect left ventricular systolic
      dysfunction. The area under the ROC curve was 0.643 (95% CI, 0.563-0.723).
      CONCLUSIONS: The BNP level and LVEF show only a weak correlation in patients with
      suspected myocardial ischemia. Neurohormonal and morphologic assessments provide
      different windows to the heart.

PMID- 17182132
TI  - Pulmonary arterial hypertension in congenital heart disease: an epidemiologic
      perspective from a Dutch registry.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) associated with congenital
      heart disease is usually the result of a large systemic-to-pulmonary shunt, and
      often leads to right ventricular failure and early death. The purpose of this
      study was to determine the prevalence of PAH among adult patients included in a
      national registry of congenital heart disease and to assess the relation between
      patient characteristics and PAH. METHODS: Patients with PAH associated with a
      septal defect were identified from the registry. Gender, age, underlying
      diagnosis, previous closure, age at repair and NYHA classification were recorded.
      PAH was defined as a systolic pulmonary arterial pressure (sPAP) greater than 40
      mm Hg, estimated by means of echocardiographical evaluation. RESULTS: The
      prevalence of PAH among all 5970 registered adult patients with congenital heart
      disease was 4.2%. Of 1824 patients with a septal defect in the registry, 112
      patients (6.1%) had PAH. Median age of these patients was 38 years (range 18-81
      years) and 40% were male. Of these patients, 58% had the Eisenmenger syndrome.
      Among the patients with a previously closed septal defect, 30 had PAH (3%).
      Ventricular septal defect (VSD) was the most frequent underlying defect (42%)
      among patients with PAH and a septal defect. Female sex (Odds ratio=1.5, p=0.001)
      and sPAP (Odds ratio=0.04, p<0.001) were independently associated with a
      decreased functional class. CONCLUSION: PAH is common in adult patients with
      congenital heart disease. In our registry the prevalence of PAH in septal defects
      is around 6%. More than half of these patients have the Eisenmenger syndrome,
      which accounts for 1% of the total population in the CONCOR registry. Whether the
      prevalence of PAH will decrease in the future as a result of early detection and
      intervention remains to be awaited.

PMID- 17182133
TI  - Patient-dependent variables affecting treatment and prediction of acute coronary
      syndrome are age-related. A study performed in Israel.
AB  - BACKGROUND: Acute coronary syndrome (ACS) prevails in older patients and is
      associated with higher morbidity and mortality. Little is known about patient
      related variables that may affect course and treatment of ACS in older vs.
      younger with acute chest pain. METHODS: Situational, circumstantial, and other
      patient-related variables were assessed in 1000 unselected consecutive older (>
      or =70 years) and younger (<70 years) patients admitted with chest pain and
      possible ACS. RESULTS: In 182 older vs. 818 younger patients, prevalence of
      females, those not speaking the local language, living alone, lower education
      level, non-smokers, diabetes, hypertension, preexisting coronary artery disease,
      and attempting some form of self-treatment before seeking medical help were
      significantly greater (P<0.001). Interval from chest pain onset to emergency
      department arrival was longer (P=0.05), and a higher proportion of the older
      considered hospitalization mandatory, suspecting ACS (P<0.001). ACS eventually
      developed in 19.1% of younger and 39% of older patients (P<0.001). On
      multivariate analysis, most predictive of ACS in the younger group were:
      preexisting coronary artery disease (OR 5.27; 95% CI 3.44-8.07, P<0.001), current
      smoking (OR 1.78; 95% CI 1.16-2.75, P=0.002), male sex (OR 1.57; 95% CI 1.0-2.59,
      P=0.07), and older age (OR 1.25; 95% CI 1.11-1.42, P=0.005). In the older group,
      these were: not speaking the local language (OR 2.39; 95% CI 1.19-4.79, P=0.005),
      preexisting coronary artery disease (OR 1.95; 95% CI 1.0-3.87, P=0.026), direct
      emergency department arrival (OR 1.9; 95% CI 1.0-3.77, P=0.066), and diabetes (OR
      1.84; 95% CI 1.0-3.56, P=0.079). CONCLUSIONS: We defined age-associated
      differences in patient-related variables that may predict ACS and affect
      treatment negatively. These variables might improve risk stratification upon
      hospitalization.

PMID- 17182134
TI  - A novel tilt table testing protocol for investigating patients suspected to have
      neurally mediated syncope.
AB  - We have observed that a series of 3 Valsalva maneuvers performed at 1-minute
      intervals between the 15th and 18th minute of a drug-free tilt table test
      resulted in intense presyncope and hypotension in a 32 yr old male with
      micturition syncope. In contrast, five apparently healthy subjects tolerated a 70
      degree head-up tilt table test for 45 min with five Valsalva maneuvers
      incorporated into the testing protocol. Thus, we hypothesize that the use of a
      series of Valsalva maneuvers during a drug free head-up tilt table test might
      improve the diagnostic yield without compromising test specificity in patients
      suspected to have neurally mediated syncope.

PMID- 17182136
TI  - Herbals in cardiovascular practice: are physicians neglecting anything?
AB  - BACKGROUND: Herbal products have been widely used by many patients with
      cardiovascular problems solely expecting benefit out of them. Since, it is
      important to consider patients' needs and believes to prevent breaking off the
      relationship of patients and physicians, we conducted a survey on patients
      admitted to our outpatient Cardiology department. METHODS: A questionnaire was
      prepared including 49 questions. After giving informed consent, 310 participants
      were enrolled into our survey. Participants were asked about disease states, use
      of herbal products and their tendencies. RESULTS: There were 169 male (mean age:
      54.7+/-13.3 years) and 141 female participants (mean age: 56.2+/-14.7 years).
      54.5% (n=169) had hypertension (HT), 48.7% (n=151) had coronary artery disease
      (CAD). Among all participants, 38.7% (n=120) stated that they have used herbals
      in part of their lives. Presence of dyslipidemia was associated with herbal use.
      Three fourths of herbal users (73.3%, n=88) stated that they thought they
      benefited some extent from the use of herbals, and 25% (n=30) of herbal users
      stated that they did not take their medicine regularly. Herbal users more
      frequently agreed the statement "herbals are beneficial when added to medicine"
      compared to nonusers (20.8% vs. 15.8%, p<0.001). CONCLUSION: Considering the
      facts that increasing interest on herbals is likely to continue by the people and
      the potentially hazardous interactions between the herbals and the drugs might be
      risky for the patients, there seems a need for closer, careful and respectful
      look for physicians onto herbal users and herbals themselves for the safety of
      population.

PMID- 17182135
TI  - Cardiovascular characterization of Pkd2(+/LacZ) mice, an animal model for the
      autosomal dominant polycystic kidney disease type 2 (ADPKD2).
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is caused by
      mutations in PKD1 or PKD2. Patients with ADPKD have an increased incidence of
      cardiac valve abnormalities and left ventricular hypertrophy. Systematic analyses
      of cardiovascular involvement have so far been performed only on genetically
      unclassified patients or on ADPKD1 patients, but not on genetically defined
      ADPKD2 patients. Even existing Pkd1 or Pkd2 mouse models were not thoroughly
      analyzed in this respect. Therefore, the aim of this project was the noninvasive
      functional cardiovascular characterization of a mouse model for ADPKD2. METHODS:
      Pkd2(+/LacZ) mice and wildtype controls were classified into 8 groups with
      respect to gender, age and genotype. In addition, two subgroups of female mice
      were analyzed for cardiac function before and during advanced pregnancy. Doppler
      echocardiographic as well as histological studies were performed. RESULTS:
      Doppler-echocardiography did not reveal significant cardiovascular changes. Heart
      rate and left ventricular (LV) length, LV mass, LV enddiastolic and LV
      endsystolic diameters did not differ significantly among the various groups when
      comparing wildtype and knockout mice. There were no significant differences
      except for a tendency towards higher maximal early and late flow velocities over
      the mitral valve in old wildtype mice. CONCLUSIONS: Non-invasive phenotyping
      using ultrasound did not reveal significant cardiovascular difference between
      adult Pkd2(+/LacZ) and WT mice. Due to the lack of an obvious renal phenotype in
      heterozygous mice, it is likely that in conventional ADPKD knock out mouse models
      severe cardiac problems appear too late to be identified during the reduced
      lifespan of the animals.

PMID- 17182137
TI  - Prognostic importance of troponin T and creatine kinase after elective
      angioplasty.
AB  - BACKGROUND: The prognostic importance of elevated cardiac enzymes after elective
      percutaneous coronary intervention has been debated. Therefore, we performed a
      prospective observational study to evaluate the prognostic value of
      postprocedural rise of troponin T and creatine kinase. METHODS: Troponin T (cut
      off value 0.05 ng/ml) and creatine kinase (cut-off value 180 IU/l with muscle
      brain fraction >4%) were measured 12 h after elective percutaneous coronary
      intervention in 713 consecutive patients without elevated troponin before the
      procedure. Primary endpoint was the combined incidence of death, myocardial
      infarction, stroke, repeat angiography or re-admission because of anginal
      symptoms during the follow-up period. RESULTS: Troponin was elevated after the
      procedure in 150 patients (21%) and creatine kinase in 66 pts (9%), with a strong
      association between increased troponin and creatine kinase. After a mean follow
      up of 10.9 months, mortality was low (1%) and not associated with increased
      troponin or creatine kinase. There was, however, a strong relation between
      postprocedural troponin and re-admission for angina (p=0.001) or myocardial
      infarction (p=0.001). Furthermore, troponin rise was significantly associated
      with an increased risk of the primary endpoint (relative risk 1.55 95% confidence
      interval 1.01-2.38). After multivariate analysis, troponin elevation but not
      increased creatine kinase was associated with an increased risk of the primary
      endpoint (relative risk 1.59 95% confidence interval 1.02-2.47 for troponin
      elevation versus 1.16 95% confidence interval 0.62-2.15 for increased creatine
      kinase). CONCLUSION: Increase of troponin T after elective percutaneous coronary
      intervention has stronger prognostic implication when compared to increased
      creatine kinase.

PMID- 17182138
TI  - Plasma brain natriuretic peptide levels, right ventricular volume overload and
      exercise capacity in adolescents after surgical repair of tetralogy of Fallot.
AB  - BACKGROUND: Right ventricular (RV) volume overload secondary to pulmonary
      regurgitation contributes to long-term morbidities in patients after tetralogy of
      Fallot (TOF) repair. We tested the hypothesis that plasma brain natriuretic
      peptide (BNP) levels relate to RV volume overload, pulmonary regurgitation, and
      exercise capacity in adolescents after TOF repair. METHODS: We assessed the RV
      function echocardiographically and plasma BNP levels in 32 postoperative TOF
      patients aged 14.7+/-3.1 years and 20 age-matched controls. Eighteen patients
      further underwent cardiovascular magnetic resonance imaging and 26 had exercise
      testing. RESULTS: Compared with controls, patients had significantly higher BNP
      levels (p=0.027), greater indexed RV end-diastolic dimension (p<0.001), increased
      RV myocardial performance index (p=0.005), and reduced tricuspid annular systolic
      velocity (p=0.008). Multivariate analysis identified indexed RV end-diastolic
      dimension as the only significant determinant of plasma BNP levels (beta=0.69,
      p<0.001). Plasma BNP levels correlated positively with indexed RV end-diastolic
      volume (r=0.6, p=0.009) and pulmonary regurgitant fraction (r=0.54, p=0.026), and
      negatively with exercise duration (r=-0.45, p=0.021), peak oxygen consumption (r=
      0.43, p=0.03), and minute ventilation at maximal exercise (r=-0.52, p=0.006).
      Multivariate analysis demonstrated BNP levels (beta=-0.43, p=0.034) and body mass
      index (beta=-0.40, p=0.036) to be independent predictors of peak oxygen
      consumption. No relations were found between BNP levels and RV myocardial
      performance index, tricuspid annular velocities and RV ejection fraction.
      CONCLUSIONS: In adolescent patients after TOF repair, plasma BNP levels relate to
      RV volume overload, pulmonary regurgitation and exercise capacity.

PMID- 17182139
TI  - No detectable Chlamydia pneumoniae and cytomegalovirus DNA in leukocytes in
      subjects with echolucent and echogenic carotid artery plaques.
AB  - BACKGROUND: Controversy exists whether persistent Chlamydia pneumoniae or
      cytomegalovirus infections cause initiation or progression of atherosclerosis. C.
      pneumoniae DNA in peripheral blood mononuclear cells (PBMC) has been proposed to
      be a more reliable marker of cardiovascular risk than are C. pneumoniae
      antibodies. Reported prevalences of C. pneumoniae DNA among cardiovascular
      patients vary greatly, indicating methodological limitations. There is an
      increasing concern that published results may have been biased by extensive use
      of less specific polymerase chain reaction (PCR) technology. METHODS: C.
      pneumoniae DNA and cytomegalovirus DNA were determined by probe-based real-time
      PCR technology in PBMCs among subjects with echolucent (n=29) or echogenic (n=28)
      carotid artery plaques, and in controls without carotid plaques (n=38), all
      recruited from a population-based study. Samples were examined in multiple
      repeats with PCR assays targeting two different sequences of the genome for both
      microorganisms. RESULTS AND CONCLUSION: IgG seropositivity was frequent in all
      three groups, confirming previous exposure, but C. pneumoniae DNA or
      cytomegalovirus DNA was not detected in a single PBMC sample by means of probe
      based, highly sensitive, and specific real-time PCR assays. Our results indicate
      that persistent C. pneumoniae or CMV infection is not a common phenomenon in
      subjects with carotid atherosclerosis.

PMID- 17182140
TI  - Acute myocardial infarction with normal coronary arteries: role of coronary
      artery spasm and arrhythmic complications.

PMID- 17182141
TI  - Rapid quantification of bacterial cells in potable water using a simplified
      microfluidic device.
AB  - A simplified microfluidic device for quantification of bacteria in potable water
      was fabricated and examined. Comparisons of counts of Escherichia coli by the
      microfluidic system and by epifluorescence microscopy closely correlated
      (r2=0.99). Bacteria in natural mineral water and in purified household tap water
      were accurately enumerated by using this system within 15 min after fluorescent
      staining.

PMID- 17182142
TI  - Long-term follow-up reveals low toxicity of radiosurgery for vestibular
      schwannoma.
AB  - AIM: The long-term effects of radiosurgery of vestibular schwannomas were
      investigated in a group of consecutively treated patients. METHODS AND MATERIALS:
      Between 1995 and 2001, 26 patients (median age: 67, range: 30-82) with a
      vestibular schwannoma were treated by Linac-based stereotactic radiosurgery
      (SRS). The median follow-up was 49 months (16-85 months). Only progressive
      tumours were treated. The median size of tumours was 18 mm (range 9-30 mm).
      Before SRS, 11 patients had a useful hearing (Gardner-Robertson classes 1 and 2).
      Single doses of 10-14 Gy were prescribed at the 80% isodose at the tumour margin.
      The follow-up consisted of regular imaging with MRI the first 3-6 months after
      the intervention, followed by additional yearly MRIs, a hearing test and a
      neurological examination. RESULT: The 5-year-probability of tumour control
      (defined as stabilization or decrease in size) was 95%. Five-year-probability of
      preservation of hearing and facial nerve function was 96% and 100%, respectively.
      Hearing was preserved in 10 out of 11 patients who had a normal or useful hearing
      at the time of treatment. Mild and transient trigeminal toxicity occurred in 2
      (8%) patients. It appeared to be significantly correlated to the dose used
      (p=0.044). However, only a tendency to significance could be demonstrated in the
      relationship between the two factors when using the Cox analysis (hazard
      ratio=1.7; 95% CI: 0.7-3.9; p=0.23). CONCLUSIONS: With the doses used, our study
      demonstrates that SRS provides an equivalent tumour control rate when compared to
      surgery, as well as on a long-term basis, an excellent preservation of the facial
      and the acoustic nerves. Although no permanent trigeminal toxicity was observed,
      our data confirm that doses below 14 Gy can avoid transient dysesthesias.

PMID- 17182143
TI  - Comparison of 6 MV and 18 MV photons for IMRT treatment of lung cancer.
AB  - BACKGROUND AND PURPOSE: To compare 6 MV and 18 MV photon intensity modulated
      radiotherapy (IMRT) for non-small cell lung cancer. MATERIALS AND METHODS: Doses
      for a cohort of 10 patients, typical for our department, were computed with a
      commercially available convolution/superposition (CS) algorithm. Final dose
      computation was also performed with a dedicated IMRT Monte Carlo dose engine
      (MCDE). RESULTS: CS plans showed higher D(95%) (Gy) for the GTV (68.13 vs 67.36,
      p=0.004) and CTV (67.23 vs 66.87, p=0.028) with 18 than with 6 MV photons. MCDE
      computations demonstrated higher doses with 6 MV than 18 MV in D(95%) for the PTV
      (64.62 vs 63.64, p=0.009), PTV(optim) (65.48 vs 64.83, p=0.014) and CTV (66.22 vs
      65.64, p=0.027). Dose inhomogeneity was lower with 18 than with 6 MV photons for
      GTV (0.08 vs 0.09, p=0.007) and CTV (0.10 vs 0.11, p=0.045) in CS but not MCDE
      plans. 6 MV photons significantly (D(33%); p=0.045) spared the esophagus in MCDE
      plans. Observed dose differences between lower and higher energy IMRT plans were
      dependent on the individual patient. CONCLUSIONS: Selection of photon energy
      depends on priority ranking of endpoints and individual patients. In the absence
      of highly accurate dose computation algorithms such as CS and MCDE, 6 MV photons
      may be the prudent choice.

PMID- 17182144
TI  - Genotypic characterization of Listeria spp. isolated from fresh water fish.
AB  - A total of 200 samples (muscles and viscera, 100 of each) of fresh water fish,
      walking catfish (Clarias batrachus) were screened for Listeria spp. All the
      samples were subjected to a two-step enrichment followed by plating on selective
      media. Confirmation of the isolates was on the basis of biochemical characters,
      haemolysis on blood agar and Christie, Atkins, Munch Petersen test. A total of 39
      isolates of Listeria spp. were recovered. Of these 26 (67%), 8 (21%), 3 (8%) and
      2 (5%) were Listeria monocytogenes, Listeria seeligeri, Listeria grayi and
      Listeria welshimeri, respectively. The isolates were subjected to a PCR assay for
      detection of the virulence-associated genes individually or together. The plcA,
      actA, hlyA and iap genes were detected in six strains, three genes (actA, hlyA
      and iap) in nine strains, the plcA, hlyA and iap in our strain, the hlyA and iap
      were in three strains, actA and hlyA in four strains, plcA and hlyA in our strain
      and hlyA in two strains. The hlyA and iap were also detected in L. seeligeri.

PMID- 17182145
TI  - PFGE genotyping and antimicrobial susceptibility of Campylobacter in retail
      poultry meat in Estonia.
AB  - In the present study, the Campylobacter isolates from retail poultry meat in
      Estonia were sero- and genotyped, and the antimicrobial susceptibility was
      determined. Forty-eight chicken (36 Estonian, 12 imported) and 22 turkey
      (imported) Campylobacter isolates from 580 raw broiler chicken (396 Estonian, 184
      imported) and 30 turkey (imported) meat samples were studied. Of the isolates, 64
      were C. jejuni, 4 C. coli, and 2 Campylobacter spp. Penner serotyping of 54 C.
      jejuni isolates revealed 11 different serotypes, and 22% of the isolates were
      nontypeable by the commercial antisera. The most common serotypes O:1,44; O:21,
      and O:55 accounted for 28%, 13%, and 13% of the isolates, respectively.
      Differences in serotype distribution were seen for chicken and turkey isolates.
      Genotypic characterization of all Campylobacter isolates (n=70) was performed by
      pulsed-field gel electrophoresis (PFGE). SmaI and KpnI yielded 29 and 34 PFGE
      types, respectively, revealing high diversity among isolates. The serotype
      distribution did not show an association with the origin of the sample, but the
      majority of the isolates sharing a similar PFGE genotype originated from one
      country. High levels of resistance to ciprofloxacin (66%), nalidixic acid (66%),
      tetracycline (44%), ampicillin (34%), and erythromycin (14%) were detected among
      the 70 Campylobacter isolates. The simultaneous resistance to two or three
      antimicrobial agents occurred in 60% of the isolates. The Campylobacter isolates
      from turkey meat had higher resistance to ampicillin, ciprofloxacin, nalidixic
      acid, and tetracycline than those from chicken meat. None of the chicken isolates
      were resistant to gentamicin, and no turkey isolates to erythromycin or
      gentamicin.

PMID- 17182146
TI  - Characterization of microflora in homemade semi-hard white Zlatar cheese.
AB  - The Zlatar cheese belongs to the group of traditionally homemade cheeses, which
      are produced from nonpasteurized cow's milk, without adding of any bacterial
      starter culture. Changes were followed in lactic acid bacteria population and
      chemical composition during the ripening period of cheese up to 60 days. Results
      showed that the percentage of lactic acid cocci was higher in raw milk and one
      day old cheese and their percentage was gradually decreasing, whereas the number
      of lactobacilli was increasing. After 30 days of cheese ripening the number of
      cocci increased again, reaching the number of lactobacilli. The results of API 50
      CH system and rep-PCR analysis showed that Lactobacillus paracasei subsp.
      paracasei, Lactobacillus brevis, Lactococcus lactis subsp. lactis, Enterococcuus
      faecium and Enterococcus faecalis were the main groups present during the
      ripening of Zlatar cheese. Results revealed that in older cheeses (45 and 60 days
      old) enterococci were the main group present. It was also demonstrated that 57
      isolates showed antimicrobial activity. The number of bacteria showing
      antimicrobial activity slowly decreased during the ripening period and in samples
      of 60 days old cheese producers of antimicrobial activities were not detected.

PMID- 17182147
TI  - Comparison of methods for detection of norovirus in oysters.
AB  - In the absence of culture methods for noroviruses, detection in foods relies on
      molecular techniques such as Reverse Transcription-Polymerase Chain Reaction (RT
      PCR) on extracted viral RNA followed by PCR product confirmation by hybridisation
      and/or sequencing. However, in order to obtain a successful detection it is of
      great importance to remove the tissue inhibitors during the viral RNA extraction.
      To select the most efficient extraction procedure of oysters we have compared
      four protocols. A pool of digestive gland material from oyster samples was
      divided into 1.5 g portions and spiked with 10-fold dilutions of human faecal
      samples containing norovirus genogroup II. The samples were tested on three
      different occasions using four different sample treatment protocols. The
      protocols were assessed with regard to their ability to recover viral RNA and
      detect norovirus in spiked oysters and for their in-house reproducibility. One
      method using viral elution by a Mixer Mill Cell Disrupter resulted in a 10-fold
      better recovery than the other three protocols when an RT-seminested PCR
      (G2SKR/COG2F and G2SKR/G2SKF) detection approach was applied. Although less
      distinctive this was also the case when NoV was detected by a single round RT-PCR
      approach using the primers JV13i and JV12y. The second most efficient method was
      a method using chloroform extraction and polyethylene precipitation.

PMID- 17182148
TI  - Bioreductive deposition of platinum nanoparticles on the bacterium Shewanella
      algae.
AB  - An environmentally friendly method using the metal ion-reducing bacterium
      Shewanella algae was proposed to deposit platinum nanoparticles. Resting cells of
      S. algae were able to reduce aqueous PtCl(6)(2-) ions into elemental platinum at
      room temperature and neutral pH within 60min when lactate was provided as the
      electron donor. Biogenic platinum nanoparticles of about 5nm were located in the
      periplasm--a preferable, cell surface location for easy recovery of biogenic
      nanoparticles.

PMID- 17182149
TI  - [Capacity and performance: ambulatory monitoring under controlled and real-life
      conditions].
AB  - OBJECTIVES: To determine the value of ambulatory monitoring in assessing human
      gait. To describe the sensors, the parameters and the ambulatory devices.
      MATERIALS AND METHODS: Literature review and practical experience about
      techniques, principles, objectives and limits. RESULTS: Accelerometry is the main
      technique for ambulatory monitoring because of its reliability, pertinence of
      signals and software developed for interpretation. Simultaneous monitoring of
      heart rate response is clinically relevant. Pedometers and actimeters can answer
      precise clinical questions about amount of walking activity. CONCLUSION:
      Ambulatory monitoring during long periods (one day or more) is important,
      especially for rehabilitation medicine because it measures the actual patient
      activity performed and participation. The simultaneous monitoring of
      environmental conditions of activity should improve the interpretation of the
      data collected.

PMID- 17182150
TI  - Assessing the impact of VOC-contaminated groundwater on surface water at the city
      scale.
AB  - This study is believed to be one of the first to assess the impact of urban VOC
      (volatile organic compound) contaminated groundwater on river-water quality at
      the city scale. A network of riverbed piezometers was used to study the 7.4-km
      urbanised reach of the River Tame that flows across the groundwater-effluent
      unconfined Triassic sandstone aquifer underlying the city of Birmingham (UK).
      Aquifer groundwater contained significant chlorinated VOC contamination due to
      the city's industrial heritage. Chlorinated VOC-contaminated baseflow was
      widespread along the reach with trichloroethene (TCE) dominant. VOC
      concentrations in riverbed piezometers were in the range 0.1-100 microg/l with
      typical regulatory limits occasionally exceeded by an order of magnitude.
      Although anaerobic biodegradation products such as cis-dichloroethene were
      widespread, they were unlikely to have formed in the generally aerobic riverbed.
      The lack of anaerobic conditions was ascribed to insufficient accumulation of low
      permeability, organic-carbon rich riverbed sediments in this medium-high energy
      river. Assumptions a priori that natural attenuation of chlorinated VOCs will
      occur via reductive dechlorination in urban riverbeds are likely in error,
      particularly where deposits of medium-high permeability exist transmitting much
      of the baseflow. Surface-water quality impacts were nevertheless still low with
      in-river TCE increasing by just 2 microg/l over the 7.4-km reach. Agreement of
      baseflow contaminant flux estimates based on five flow-concentration product
      methods was achieved to within an order of magnitude with 22-200 kg/yr of TCE
      estimated to discharge to the 7.4-km reach (equivalent to 0.8-7.5 mg/d/m2 of
      riverbed). Such uncertainty was not regarded as unreasonable when the large
      measurement scale and geological and chemical heterogeneities are considered.
      Improved flux estimation methods and greater monitoring densities are
      nevertheless warranted. Considering Birmingham's long industrial history and
      known incidence of VOC-contaminated groundwater, the city-scale impact of VOC
      contaminated groundwater upon surface-water quality was judged to be relatively
      modest.

PMID- 17182151
TI  - Quantifying urban river-aquifer fluid exchange processes: a multi-scale problem.
AB  - Groundwater-river exchanges in an urban setting have been investigated through
      long term field monitoring and detailed modelling of a 7 km reach of the Tame
      river as it traverses the unconfined Triassic Sandstone aquifer that lies beneath
      the City of Birmingham, UK. Field investigations and numerical modelling have
      been completed at a range of spatial and temporal scales from the metre to the
      kilometre scale and from event (hourly) to multi-annual time scales. The
      objective has been to quantify the spatial and temporal flow distributions
      governing mixing processes at the aquifer-river interface that can affect the
      chemical activity in the hyporheic zone of this urbanised river. The hyporheic
      zone is defined to be the zone of physical mixing of river and aquifer water. The
      results highlight the multi-scale controls that govern the fluid exchange
      distributions that influence the thickness of the mixing zone between urban
      rivers and groundwater and the patterns of groundwater flow through the bed of
      the river. The morphologies of the urban river bed and the adjacent river bank
      sediments are found to be particularly influential in developing the mixing zone
      at the interface between river and groundwater. Pressure transients in the river
      are also found to exert an influence on velocity distribution in the bed
      material. Areas of significant mixing do not appear to be related to the areas of
      greatest groundwater discharge and therefore this relationship requires further
      investigation to quantify the actual remedial capacity of the physical hyporheic
      zone.

PMID- 17182152
TI  - Groundwater-surface water interaction and its role on TCE groundwater plume
      attenuation.
AB  - A field investigation of a TCE plume in a surficial sand aquifer shows that
      groundwater-surface water interactions strongly influence apparent plume
      attenuation. At the site, a former industrial facility in Connecticut, depth
      discrete monitoring along three cross-sections (transects) perpendicular to
      groundwater flow shows a persistent VOC plume extending 700 m from the DNAPL
      source zone to a mid-size river. Maximum TCE concentrations along a transect 280
      m from the source were in the 1000s of microg/L with minimal degradation
      products. Beyond this, the land surface drops abruptly to a lower terrace where a
      shallow pond and small streams occur. Two transects along the lower terrace, one
      midway between the facility and river just downgradient of the pond and one along
      the edge of the river, give the appearance that the plume has strongly
      attenuated. At the river, maximum TCE concentrations in the 10s of microg/L and
      similar levels of its degradation product cis-DCE show direct plume discharge
      from groundwater to the river is negligible. Although degradation plays a role in
      the strong plume attenuation, the major attenuation factor is partial groundwater
      plume discharge to surface water (i.e. the pond and small streams), where some
      mass loss occurs via water-air exchange. Groundwater and stream mass discharge
      estimates show that more than half of the plume mass discharge crossing the first
      transect, before surface water interactions occur, reaches the river directly via
      streamflow, although river concentrations were below detection due to dilution.
      This study shows that groundwater and surface water concentration measurements
      together provide greater confidence in identifying and quantifying natural
      attenuation processes at this site, rather than groundwater measurements alone.

PMID- 17182153
TI  - Epigenetic memory loss in aging oligodendrocytes in the corpus callosum.
AB  - In this study, we address the hypothesis that aging modifies the intrinsic
      properties of oligodendrocytes, the myelin-forming cells of the brain. According
      to our model, an "epigenetic memory" is stored in the chromatin of the
      oligodendrocyte lineage cells and is responsible for the maintenance of a mature
      phenotype, characterized by low levels of expression of transcriptional
      inhibitors. We report here an age-related decline of histone deacetylation and
      methylation, the molecular mechanisms responsible for the establishment and
      maintenance of this "epigenetic memory" of the differentiated state. We further
      show that lack of histone methylation and increased acetylation in mature
      oligodendrocytes are associated with global changes in gene expression, that
      include the re-expression of bHLH inhibitors (i.e. Hes5 and Id4) and precursor
      markers (i.e. Sox2). These changes characteristic of the "aging" oligodendrocytes
      can be recapitulated in vitro, by treating primary oligodendrocyte cultures with
      histone deacetylase inhibitors. Thus, we conclude that the "epigenetic memory
      loss" detected in white matter tracts of older mice induces global changes of
      gene expression that modify the intrinsic properties of aged oligodendrocytes and
      may functionally modulate the responsiveness of these cells to external stimuli.

PMID- 17182154
TI  - Specificities of acetoxy derivatives of coumarins, biscoumarins, chromones,
      flavones, isoflavones and xanthones for acetoxy drug: protein transacetylase.
AB  - The earlier work carried out in our laboratory led to the identification of a
      novel rat liver microsomal enzyme termed as acetoxy drug: protein transacetylase
      (TAase), catalyzing the transfer of acetyl group from polyphenolic acetates (PA)
      to functional proteins. In this paper, we have reported the comparison of the
      specificities of acetoxy derivatives of coumarins, biscoumarins, chromones,
      flavones, isoflavones and xanthones with special reference to the phenyl
      moiety/bulky group on the pyran ring of PA. The results clearly indicated that
      compounds having phenyl moieties, when used as the substrates, resulted in a
      significant reduction of TAase catalyzed activity. The alteration in TAase
      catalyzed activation of NADPH cytochrome c reductase and inhibition of benzene
      induced micronuclei in bone marrow cells by PA were in tune with their
      specificities to TAase.

PMID- 17182156
TI  - Effect of footwear and orthotic devices on stress reduction and soft tissue
      strain of the neuropathic foot.
AB  - BACKGROUND: Ground reaction forces from walking result in stress (pressure) and
      soft tissue strain at the plantar aspect of the foot. Excessive plantar pressure
      and tissue strain on the insensate foot may lead to ulceration. Our study
      investigated the effect of therapeutic footwear and custom-made orthotic inserts
      on pressure and tissue strain along the second ray of the plantar foot, and how
      these two variables are associated. METHODS: Twenty subjects (mean age 57.3 [SD
      9.3] years, 12 male, 8 female, body mass index 32.5 [SD 7.4] kg/m2) with diabetes
      mellitus, peripheral neuropathy, and a history of a plantar ulcer participated.
      Plantar pressure data were recorded during computed tomography scans for four
      conditions (barefoot, shoe, shoe+total contact insert, and shoe+total contact
      insert+metatarsal pad). For each condition tested, tissue strain and plantar
      pressure were determined at the second metatarsal head and at 15 other points
      along the second ray. FINDINGS: Differences were noted between the 4 conditions
      for pressure (P<0.004) and soft tissue strain (P<0.042) at the second metatarsal
      head. Correlation coefficients demonstrated an association between pressure and
      strain (Barefoot r=0.81, Shoe r=0.75, Shoe+total contact insert r=0.73, and
      Shoe+total contact insert+metatarsal pad r=0.44). INTERPRETATION: Footwear and
      orthotic devices tested in this study decreased pressure and soft tissue strain
      at the second ray of the foot, and these two variables were strongly related. A
      better understanding of the role tissue strain plays in distributing plantar
      forces may lead to improvements in the design of orthotic devices.

PMID- 17182157
TI  - Adsorption and absorption of polycyclic aromatic hydrocarbons to rice roots.
AB  - Rice roots and surrounding air, soil and water samples were collected for
      polycyclic aromatic hydrocarbon (PAH) analysis. The rice roots were separated
      into lateral roots and nodal roots, and the PAH concentration in the former was
      found to be higher than that in the latter. In addition, root physiological
      characteristics including root biotic mass, root lipid content and specific
      surface area are also discussed. When normalizing the total, adsorption and
      absorption PAH fractions on a dry root weight basis to root biomass, root lipid,
      and surface area bases respectively, the differences between PAHs in the two
      types of roots diminished by 2 to 3 times on average. Results from sequential
      extraction indicated that PAHs were more easily absorbed by interior rice roots
      than adsorbed on the surface. In addition, more than 60% of total PAHs
      accumulated in root tissue for both lateral and nodal roots. However, the results
      were highly related to the solvent used, extraction time and methodology.
      Correlation analysis between bioconcentration factors (root over environment) and
      K(OA), K(OW) showed water to be more significant for PAH adsorption in rice roots
      than other environmental media.

PMID- 17182155
TI  - Cell-mediated immune responses in humans after immunization with one or two doses
      of oral live attenuated typhoid vaccine CVD 909.
AB  - CVD 909 is a novel live attenuated S. Typhi oral vaccine candidate derived from
      strain CVD 908-htrA which constitutively expresses Vi. Herein we investigated
      whether the genetic manipulations involved in modifying CVD 908-htrA altered its
      ability to induce potent T-cell immune responses (CMI) after a single dose (five
      subjects) and, in a separate trial, whether a second dose (eight subjects)
      further enhanced its immunogenicity. In these clinical trials we observed that
      CVD 909 immunization elicits a wide array of CMI, including cytotoxic T cells
      (CTL), IFN-gamma, TNF-alpha and IL-10 (but not IL-2, IL-4 or IL-5) production,
      and proliferation to S. Typhi antigens. However, the administration of a second
      dose did not result in increases in CMI. These results suggest that the genetic
      manipulations to constitutively express Vi did not adversely affect the ability
      of CVD 909 to elicit a wide array of CMI responses. These observations add
      impetus for the continuing evaluation of CVD 909 as a typhoid vaccine candidate.

PMID- 17182159
TI  - Essential and non-essential element concentrations in two sleeper shark species
      collected in arctic waters.
AB  - A number of elements/metals have increased in arctic biota and are of concern due
      to their potential toxicity. Most studies on elements in the Arctic have focused
      on marine mammals and seabirds, but concentrations in the Greenland shark
      (Somniosus microcephalus) and Pacific sleeper shark (Somniosus pacificus), the
      only two shark species known to regularly inhabit arctic waters, have never been
      reported. To address this data gap, concentrations and patterns of 25 elements
      were analyzed in liver of Greenland sharks collected about Cumberland Sound
      (n=24) and Pacific sleeper sharks collected about Prince William Sound (n=14).
      Several non-essential elements differed between species/locations, which could
      suggest geographical exposure differences or ecological (e.g., diet) differences
      between the species. Certain essential elements also differed between the two
      sleeper sharks, which may indicate different physiological requirements between
      these closely related shark species, although information on such relationships
      are lacking for sharks and fish.

PMID- 17182160
TI  - Hemispheric visual atentional imbalance in patients with traumatic brain injury.
AB  - We find a spatially asymmetric allocation of attention in patients with traumatic
      brain injury (TBI) despite the lack of obvious asymmetry in neurological
      indicators. Identification performance was measured for simple spatial patterns
      presented briefly to a locus 5 degrees into the left or right hemifield, after
      precuing attention to the same (ipsilateral) or opposite (cross-hemifield) side.
      Though the cue was non-predictive of target location overall, performance was
      significantly slower for cross than for ipsilateral trials in both patients and
      controls. We tested 21 TBI patients without overt focal brain damage and nine
      control subjects. Only patients demonstrated significantly worse performance for
      left side presentation in the ipsilateral condition. Furthermore, in the cross
      hemifield condition, the left-right difference seen in TBI patients was
      significantly larger-reflecting a failure in producing a leftward attention
      shift. Again no significant difference was found in controls. These hemifield
      effects suggest an asymmetry in the ability of TBI patients in shifting attention
      to the left hemifield, whether from central fixation or from a cue in the contra
      lateral hemifield. The results support basic hypotheses regarding visual
      attention: Attentional control may be asymmetric and attention may be a
      distributed, rather than localized cortical function.

PMID- 17182161
TI  - Stroke and cognition: what's hot. Abstracts from the 16th annual conference of
      the Rotman Research Institute. March 5-7, 2006. Toronto, Ontario, Canada.

PMID- 17182158
TI  - Phosphorus supply influences heathland responses to atmospheric nitrogen
      deposition.
AB  - On an upland moor dominated by pioneer Calluna vulgaris and with an understorey
      of mosses and lichens, experimental plots were treated with factorial
      combinations of nitrogen (N) at +0 and +20kg Nha(-1)yr(-1), and phosphorus (P) at
      +0 and +5kg Pha(-1)yr(-1). Over the 4-year duration of the experiment, the cover
      of the Calluna canopy increased in density over time as part of normal
      phenological development. Moss cover increased initially in response to N
      addition but then remained static; increases in cover in response to P addition
      became stronger over time, eventually causing reductions in the cover of the
      dominant Calluna canopy. Lichen cover virtually disappeared within 4 years in
      plots receiving +20kg Nha(-1)yr(-1) and also in separate plots receiving +10kg
      Nha(-1)yr(-1), but this effect was reversed by the addition of P.

PMID- 17182162
TI  - Aging and strategic retrieval in a cued-recall test: the role of executive
      functions and fluid intelligence.
AB  - Cued-recall in episodic memory was investigated in relation to low and high
      cognitive support at retrieval, executive function level and fluid intelligence
      level in 81 healthy adults divided first into two age groups (young and elderly
      adults). The first analyses showed that age-related differences were greater when
      a low cognitive support was provided to recall the words. An individual index of
      loss of performance when the number of cues was decreased was then calculated.
      Hierarchical regression analysis revealed that the executive functions measure
      (perseverative errors on the Wisconsin Card Sorting Test) was a better candidate
      than the fluid intelligence measure (Cattell's culture fair test) to account for
      the age-related variance of the size of performance loss. These findings suggest
      that age differences in implementing strategic retrieval may be mainly due to a
      decline in executive functions.

PMID- 17182163
TI  - Separation stress, litter size, and the rewarding effects of low-dose morphine in
      the dams of maternally separated rats.
AB  - Potential differences in sensitivity to the rewarding effects of morphine as a
      function of litter separation stress were assessed in post-weaning rat dams.
      During the first two weeks postnatal, Sprague-Dawley rat litters were subjected
      to daily 15- or 180-min sessions of dam-pup separation while control litters only
      experienced twice-weekly animal facility care. One week after weaning, the dams
      (n=7 per group) underwent a fully unbiased conditioned place preference (CPP)
      procedure to 1 mg/kg subcutaneous morphine. CPP responses after each conditioning
      cycle were recorded. Rates of acquisition and asymptotic levels of CPP were
      comparable in all groups; however, an inverse relationship between litter size
      and magnitude of morphine CPP was revealed. Although these initial data indicate
      no differential sensitivity to the rewarding effects of low-dose morphine
      produced by the stress of litter separation, this assessment of litter size and
      drug-induced place conditioning in post-weaning litter-separated dams is the
      first of its kind. Potential effects of other doses, drugs of abuse and post
      partum manipulations remain to be evaluated within this emerging etiological
      model.

PMID- 17182164
TI  - Antidepressant-like effect of the extract from leaves of Schinus molle L. in
      mice: evidence for the involvement of the monoaminergic system.
AB  - Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the
      treatment of depression. In this study, the antidepressant-like effect of the
      hexanic extract from leaves of S. molle was investigated in the mouse tail
      suspension test (TST), a predictive model of depression. The immobility time in
      the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.),
      without accompanying changes in ambulation when assessed in an open-field test.
      The efficacy of extract was found to be comparable to that of fluoxetine (10
      mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was
      prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA,
      100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days),
      NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg,
      s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5
      HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor
      antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist),
      yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05
      mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2)
      receptor antagonist). It may be concluded that the hexanic extract of S. molle
      produces an antidepressant-like effect that seems to be dependent on its
      interaction with the serotonergic, noradrenergic and dopaminergic systems. These
      results provide evidence that the extract from S. molle shares with established
      antidepressants some pharmacological effects, at least at a preclinical level.

PMID- 17182165
TI  - The role of vagal function in the risk for cardiovascular disease and mortality.
AB  - Cardiovascular disease (CVD) is the leading cause of death and disability
      worldwide. The understanding of the risk factors for CVD may yield important
      insights into the prevention, etiology, course, and treatment of this major
      public health concern. We review the evidence for the role of vagal function in
      the risk for cardiovascular disease and mortality. Using a broad range of
      indicators of vagal function including resting heart rate, heart rate recovery,
      heart rate variability, and baroreflex sensitivity we show that decreased vagal
      function is associated with an increased risk for morbidity and mortality. These
      effects are independent of traditional risk factors. Moreover, we show that
      decreased vagal function is associated with both traditional and emerging risk
      factors as well as modifiable and non-modifiable risk factors. Most importantly,
      we provide evidence to support the notion that decreased vagal function precedes
      the development of a number of risk factors and that modification of risk
      profiles in the direction of lower risk is associated with increased vagal
      function. We close with a brief overview of the neural concomitants of vagal
      function and suggest that a model of neurovisceral integration may provide a
      unifying framework within which to investigate the impact of risk factors,
      including psychosocial factors, on cardiovascular disease.

PMID- 17182166
TI  - Small uterine septum is an important risk variable for preterm birth.
AB  - OBJECTIVE(S): To evaluate whether a uterus with a small septum (arcuate uterus or
      class VI according to the American Fertility Society (AFS) classification)
      behaves similarly to a uterus with a larger septum (septate or subseptate uterus
      or AFS class V). STUDY DESIGN: Observational study included 826 singleton
      deliveries to 730 women with a history of hysteroscopic resection of the uterine
      septum. Data on deliveries were obtained from the National Perinatal Registry of
      Slovenia (NPIS). Multiple gestations were excluded. We analysed and compared
      perinatal outcomes before and after hysteroscopic resection in two groups of
      women: in women with a small uterine septum (Group A) and in those with a larger
      uterine septum (Group B). Data on the septum length were obtained during
      hysteroscopic resection by comparing the length of the 1.4-cm long yellow tip of
      the electric knife to the length of the resected septum. A small uterine septum
      was defined as having a length of 1.3-1.5 cm. RESULTS: The preterm birth rate in
      Group A (n=420) was 33.9% before and 7.2% after hysteroscopic resection
      (P<0.001); the preterm birth rate in Group B (n=406) was 36.5% before and 8.0%
      after hysteroscopic resection (P<0.001). The very preterm birth rate in Group A
      was 12.5% before and 3.1% after hysteroscopic resection (P<0.001); the very
      preterm birth rate in Group B was 15.0% before and 2.9% after hysteroscopic
      resection (P<0.001). After surgery, we registered a decreased need for neonatal
      intensive care, as well as a significant decrease in stillbirth and neonatal
      death rates in both groups of patients. CONCLUSION(S): Similarly to a large
      uterine septum, a small uterine septum or arcuate uterus is an important
      hysteroscopically preventable risk variable for preterm birth.

PMID- 17182167
TI  - The study of amorphous aggregation of tobacco mosaic virus coat protein by
      dynamic light scattering.
AB  - The kinetics of heat-induced and cetyltrimethylammonium bromide induced amorphous
      aggregation of tobacco mosaic virus coat protein in Na(+)/Na(+) phosphate buffer,
      pH 8.0, have been studied using dynamic light scattering. In the case of thermal
      aggregation (52 degrees C) the character of the dependence of the hydrodynamic
      radius (R(h)) on time indicates that at certain instant the population of
      aggregates is split into two components. The size of the aggregates of one kind
      remains practically constant in time, whereas the size of aggregates of other
      kind increases monotonously in time reaching the values characteristic of
      aggregates prone to precipitation (R(h)=900-1500 nm). The construction of the
      light scattering intensity versus R(h) plots shows that the large aggregates (the
      start aggregates) exist in the system at the instant the initial increase in the
      light scattering intensity is observed. For thermal aggregation the R(h) value
      for the start aggregates is independent of the protein concentration and equal to
      21.6 nm. In the case of the surfactant-induced aggregation (at 25 degrees C) no
      splitting of the aggregates into two components is observed and the size of the
      start aggregates turns out to be much larger (107 nm) than on the thermal
      aggregation. The dependence of R(h) on time for both heat-induced aggregation and
      surfactant-induced aggregation after a lapse of time follows the power law
      indicating that the aggregation process proceeds in the kinetic regime of
      diffusion-limited cluster-cluster aggregation. Fractal dimension is close to 1.8.
      The molecular chaperone alpha-crystallin does not affect the kinetics of tobacco
      mosaic virus coat protein thermal aggregation.

PMID- 17182168
TI  - Interaction of cationic vesicle with ribonucleotides (AMP, ADP, and ATP) and
      physicochemical characterization of DODAB/ribonucleotides complexes.
AB  - The interaction between ribonucleotides (AMP, ADP, and ATP) and cationic vesicles
      prepared from dioctadecyldimethylammonium bromide (DODAB) were investigated in
      detail. The physicochemical properties of ribonucleotides/cationic lipid
      complexes were present. Gel exclusion-UV spectroscopic results showed that all
      the charge ratios of DODAB/ribonucleotides (AMP, ADP, and ATP) are 2:1 when the
      maximal ribonucleotides were adsorbed onto DODAB, while the molar ratios were
      different, e.g., 2:1 for DODAB/AMP, 4:1 for DODAB/ADP and 6:1 for DODAB/ATP.
      These differences may be attributed to the different anion charges of AMP, ADP
      and ATP. The results demonstrated that ribonucleotides combined with DODAB
      vesicles with the electrostatic attraction in the complexation of DODAB and
      ribonucleotides. Transmission electron microscopic results revealed the different
      extents of aggregation of cationic vesicles in the complexation process of
      ribonucleotides with cationic lipid. The variation dependence of zeta-potentials
      or electrophoretic mobilities on vesicle size was also different. The zeta
      potentials and electrophoretic mobilities of the DODAB vesicles (0.01 and 0.02
      mM) gradually decreased when the ribonucleotide concentration increased. However,
      the mean diameters of the DODAB vesicles (0.1 and 0.5 mM) gradually increased
      when the ribonucleotide concentration increased.

PMID- 17182169
TI  - Enhancing forest carbon sequestration in China: toward an integration of
      scientific and socio-economic perspectives.
AB  - This article serves as an introduction to this special issue, "China's Forest
      Carbon Sequestration", representing major results of a project sponsored by the
      Canadian International Development Agency and the Chinese Academy of Sciences.
      China occupies a pivotal position globally as a principle emitter of carbon
      dioxide, as host to some of the world's largest reforestation efforts, and as a
      key player in international negotiations aimed at reducing global greenhouse gas
      emission. The goals of this project are to develop remote sensing approaches for
      quantifying forest carbon balance in China in a transparent manner, and
      information and tools to support land-use decisions for enhanced carbon
      sequestration (CS) that are science based and economically and socially viable.
      The project consists of three components: (i) remote sensing and carbon modeling,
      (ii) forest and soil assessment, and (iii) integrated assessment of the socio
      economic implications of CS via forest management. Articles included in this
      special issue are highlights of the results of each of these components.

PMID- 17182170
TI  - Is benign prostatic hyperplasia (BPH) an immune inflammatory disease?
AB  - OBJECTIVES: Chronic inflammation has been documented for years in benign
      prostatic hyperplasia (BPH), but only now has it become evident as a major factor
      in disease progression. This review highlights the immunologic key features of
      chronic inflammation in BPH and the present interpretation of these changes in
      the development and progression of BPH. RESULTS: Almost all BPH specimens show
      inflammatory infiltrates at histologic examination, but correlation to bacterial
      or other foreign antigens has not been established. Recognition of prostate
      secretion products by autoreactive T cells and animal models on experimental
      prostatitis demonstrate an autoimmune component to chronic inflammation. The
      infiltrate consists predominantly of chronically activated CD4(+) T lymphocytes,
      which are permanently recruited to prostate tissue via elevated expression of
      interleukin 15 (IL-15) and interferon gamma (IFN-gamma), proinflammatory
      cytokines produced by smooth muscle and T cells, respectively. With the
      appearance of infiltrates, T cell-derived cytokine production of IFN-gamma, IL-2,
      and transforming growth factor beta increases, the former two ultimately reaching
      10-fold and the latter 2-fold higher levels in fully developed BPH than in normal
      prostates. As "mature" BPH nodules develop, IL-4 and IL-13 expression increases
      >2-fold, corresponding to a T-helper (Th)0/Th2 cytokine pattern. Dysregulation of
      the immune response in BPH may occur via elevated expression of proinflammatory
      IL-17, which stimulates a multifold production of IL-6 and IL-8, key executors of
      stromal growth in BPH. CONCLUSIONS: These data strongly suggest that BPH is an
      immune inflammatory disease. Unravelling the specific nature of immune
      dysregulation may help design novel drugs with these specific targets in mind.

PMID- 17182171
TI  - Keyword extraction, ranking, and organization for the neuroinformatics platform.
AB  - Brain-related researches encompass many fields of studies and usually involve
      worldwide collaborations. Recognizing the value of these international
      collaborations for efficient use of resources and improving the quality of brain
      research, the International Neuroinformatics Coordinating Facility (INCF) started
      to coordinate the effort of establishing neuroinformatics (NI) centers and portal
      sites among the different participating countries. These NI centers and portal
      sites will serve as the conduit for the interchange of information and brain
      related resources among different countries. In Japan, several NI platforms under
      the support of NIJC (NI Japan Center) are being developed with one platform
      called, Visiome, already operating and publicly accessible at
      "http://www.platform.visiome.org". Each of these platforms requires their own set
      of keywords that represent important terms covering their respective fields of
      study. One important function of this predefined keyword list is to help
      contributors classify the contents of their contributions and group related
      resources. It is vital, therefore, that this predefined list should be properly
      chosen to cover the necessary areas. Currently, the process of identifying these
      appropriate keywords relies on the availability of human experts which does not
      scale well considering that different areas are rapidly evolving. This problem
      prompted us to develop a tool to automatically filter the most likely terms
      preferred by human experts. We tested the effectiveness of the proposed approach
      using the abstracts of the Vision Research Journal (VR) and Investigative
      Ophthalmology and Visual Science Journal (IOVS) as source files.

PMID- 17182172
TI  - The growth plate sparing effects of the selective glucocorticoid receptor
      modulator, AL-438.
AB  - Long-term use of glucocorticoids (GC) can cause growth retardation in children
      due to their actions on growth plate chondrocytes. AL-438, a non-steroidal anti
      inflammatory agent that acts through the glucocorticoid receptor (GR) retains
      full anti-inflammatory efficacy but has reduced negative effects on osteoblasts
      compared to those elicited by prednisolone (Pred) or dexamethasone (Dex). We have
      used the murine chondrogenic ATDC5 cell line to compare the effects of AL-438
      with those of Dex and Pred on chondrocyte dynamics. Dex and Pred caused a
      reduction in cell proliferation and proteoglycan synthesis, whereas exposure to
      AL-438 had no effect. LPS-induced IL-6 production in ATDC5 cells was reduced by
      Dex or AL-438, showing that AL-438 has similar anti-inflammatory efficacy to Dex
      in these cells. Fetal mouse metatarsals grown in the presence of Dex were shorter
      than control bones whereas AL-438 treated metatarsals paralleled control bone
      growth. These results indicate that the adverse effects Dex or Pred have on
      chondrocyte proliferation and bone growth were attenuated following AL-438
      exposure, suggesting that AL-438 has a reduced side effect profile on
      chondrocytes compared to other GCs. This could prove important in the search for
      new anti-inflammatory treatments for children.

PMID- 17182173
TI  - Human Thyroid Oxidases genes promoter activity in thyrocytes does not appear to
      be functionally dependent on Thyroid Transcription Factor-1 or Pax8.
AB  - Thyroid Oxidases (ThOX/DUOX) genes encode proteins that are thought to play a
      crucial role in the biosynthesis of thyroid hormone by providing the oxidizing
      agent required to allow the organification of iodine. The expression of these
      genes is not restricted to the thyroid, but the corresponding mRNAs are found in
      the thyrocyte more abundantly than in several other cell types. It raises the
      question whether the same transcription factors, namely Thyroid Transcription
      Factor-1 (TTF-1) and Pax8, that control the expression of other genes involved in
      the differentiated thyroid function, also regulate ThOX/DUOX gene transcription
      in the thyrocyte. We set up a functional co-transfection assay in which fusion
      proteins composed of the DNA-binding domain of either TTF-1 or Pax8 fused to the
      repressive domain of the drosophila engrailed protein were used to competitively
      counteract the activity of endogenous TTF-1 or Pax8 factor in the differentiated
      thyroid cell line PCCl3. Contrary to the Thyroglobulin or Thyroid Peroxidase
      promoter, the known regulatory elements of the human ThOX/DUOX genes displayed no
      reduction in transcriptional activity when either TTF-1 or Pax8 competitor was
      produced in the cell, indicating that the presently characterized control
      elements of human ThOX/DUOX genes are not responsive to these thyroid-specific
      transcription factors.

PMID- 17182174
TI  - Spontaneous resolution of acute cranial subdural hematomas.
AB  - Acute cranial subdural hematoma (SDH) represents a common consequence of
      traumatic brain injury. The vast majority of acute SDHs larger than 10mm in
      thickness require immediate surgical evacuation. In rare occasions, however,
      spontaneous resolution may occur. In our current communication, we present four
      cases of spontaneous resolution of acute cranial SDH. Further more, the proposed
      theories explaining spontaneous resolution of acute SDH, as well as, clinical
      parameters and imaging characteristics that might predict such phenomenon, are
      also reviewed. The possibility of spontaneous resolution of an acute SDH,
      although remote, may impact the decision making process regarding the management
      of these patients under certain conditions.

PMID- 17182175
TI  - Ovarian cancer survival and polymorphisms in hormone and DNA repair pathway
      genes.
AB  - We evaluated the association between 21 polymorphisms in hormone and DNA repair
      pathway genes and survival among 454 Australian women diagnosed with invasive
      epithelial ovarian cancer. The cohort was followed for mortality using personal
      identifiers which were linked to state cancer registry records and the Australian
      National Death Index. The mean follow-up time after ovarian cancer diagnosis was
      4.63 years (all women) and 8.07 years for the censored group (those alive or dead
      from non-ovarian cancer causes). Two hundred and eighty-eight (63%) ovarian
      cancer deaths occurred during the follow-up period. No association was observed
      for the vast majority of polymorphisms, but there was suggestive evidence for
      altered risk of ovarian cancer death associated with the CYP17 5'UTR C allele (HR
      1.30; 95% CI=1.02-1.68, p= 0.04), and for the SRD5A2 V89L C allele (HR 0.79; 95%
      CI=0.62-1.01, p=0.06). These results are interesting given tentative evidence
      that both of these variants are also associated with increased predisposition to
      ovarian cancer in our extended Australian study, and in other published studies.
      However, given the marginal significance of these associations and the large
      number of tests performed, independent replication will be necessary to validate
      these novel findings.

PMID- 17182177
TI  - Downregulation and CpG island hypermethylation of NES1/hK10 gene in the
      pathogenesis of human gastric cancer.
AB  - The normal epithelial cell-specific-1 (NES1)/Kallikrein 10 gene is proposed to be
      a novel putative tumor suppressor gene in several malignant diseases. The role of
      NES1 gene in gastric cancer has not been fully understood. Our study revealed
      that CpG island hypermethylation plays an important role in the downregulation of
      NES1 mRNA expression in gastric cancer. In situ hybridization showed that loss or
      reduction of NES1 mRNA expression is associated with differentiation level during
      tumor progression suggesting that NES1 inactivation might contribute to the
      malignant progression of human gastric cancers.

PMID- 17182176
TI  - Epidemiology of colonic aberrant crypt foci: review and analysis of existing
      studies.
AB  - Since first described in a rodent model in 1987, aberrant crypt foci (ACF) in the
      colon have been shown to exhibit many of the molecular features of the more
      advanced colonic neoplasms including cancer. Therefore, they may be early lesions
      with potential for progression, and be valuable biomarkers for reduction of risk
      of colorectal cancer (CRC). For this review, we searched PubMed, and reference
      lists of recent publications, for studies which reported on associations of
      features of ACF in humans, such as number or size, with subject characteristics,
      such as age or family history of CRC. Over 150 papers have reported on ACF in
      humans. However, the vast majority of these publications are concerned with
      molecular and morphological features of biopsied lesions, and not their
      epidemiology. None of the epidemiological studies were of optimum design,
      primarily due to their absence of a well-defined subject sampling frame or
      method. Given their 'first-generation' nature, consistent findings were of
      increased ACF number with age and with synchronous advanced colonic neoplasia.
      One study reported a higher mean number of ACF in subjects with a family history
      of CRC than in those without. The strongest evidence on the ability of ACF to
      predict a diagnosis of CRC will be from prospective studies with baseline ACF
      assessment in a large sample of disease-free persons (many thousands) who are
      followed carefully for many years. In the interim, because ACF are asymptomatic,
      well-designed cross-sectional studies are feasible and will yield valuable
      information on the relation of ACF to the known risk factors for CRC. This
      information can then be used to improve the design of prospective studies, and of
      clinical intervention trials that use ACF as an intermediate endpoint.

PMID- 17182178
TI  - Identification of an HLA-A*0201 restricted Bcl2-derived epitope expressed on
      tumors.
AB  - A large number of human tumor-associated antigen-derived peptides have been
      identified that are recognized by CTLs in a MHC-I restricted fashion. The
      apoptosis inhibitory protein Bcl2 is overexpressed in many human cancers as part
      of their neoplastic phenotype. Since inhibition or loss of Bcl2 expression might
      impair tumor growth and survival, this protein may serve as a rational target for
      vaccine-induced CTL responses. By Western blot technique, we screened a panel of
      established human tumor cell lines for proteins involved in the apoptotic
      process. Two of eight tumor cell lines, a B lymphoma (Loukes) and a colon
      carcinoma (CCL220) cell line showed increased Bcl2 protein expression whereas the
      majority of tumor cell lines expressed proapoptotic proteins. Neither fibroblasts
      nor peripheral blood mononuclear cells showed Bcl2 expression. An HLA-A*0201
      restricted CTL epitope was deduced in silica from the amino acid sequence of the
      Bcl2 protein and its binding affinity for HLA-A*0201 was confirmed using a
      biochemical binding assay. We here demonstrate that the 9-mer peptide Bcl2(85-93)
      induces specific CTL reactivity in immunized C57-A2K(b) or -A2D(b) tg mice. These
      Bcl2(85-93) specific CTLs react with and lyse Bcl2-expressing human colon
      carcinoma CCL220 cells which have been transfected with a chimeric HLA-A*0201/H2
      K(b) DNA construct similar to that expressed in the transgenic mice. Based on
      these observations, we suggest that Bcl2(85-93) may be a target for immune
      therapy.

PMID- 17182179
TI  - Prediction of N-nitrosodimethylamine (NDMA) formation as a disinfection by
      product.
AB  - This study investigated the possibility of a statistical model application for
      the prediction of N-nitrosodimethylamine (NDMA) formation. The NDMA formation was
      studied as a function of monochloramine concentration (0.001-5mM) at fixed
      dimethylamine (DMA) concentrations of 0.01mM or 0.05mM. Excellent linear
      correlations were observed between the molar ratio of monochloramine to DMA and
      the NDMA formation on a log scale at pH 7 and 8. When a developed prediction
      equation was applied to a previously reported study, a good result was obtained.
      The statistical model appears to predict adequately NDMA concentrations if other
      NDMA precursors are excluded. Using the predictive tool, a simple and approximate
      calculation of NDMA formation can be obtained in drinking water systems.

PMID- 17182180
TI  - Utilization of municipal solid waste incineration (MSWI) fly ash in blended
      cement Part 2. Mechanical strength of mortars and environmental impact.
AB  - This second of two articles dealing with the utilization of MSWI fly ash in
      blended cement studies the effects of two variants of the stabilization process
      on the behavior of the treated fly ash (TFA) introduced into cement-based
      mortars. From a technological point of view, the modifications of the process are
      very efficient and eliminate the swelling produced by the introduction of MSWI
      fly ash in cement-based mortars. TFA has a significant activity in cement-based
      mortars and can also advantageously replace a part of the cement in cement-based
      material. From an environmental point of view, the results of traditional
      leaching tests on monolithic and crushed mortars highlight a poor stabilization
      of some harmful elements such as antimony and chromium. The use of a cement rich
      in ground granulated blast furnace slag (GGBFS) with a view to stabilizing the
      chromium is not efficient. Since neither adequate tests nor quality criteria
      exist to evaluate the pollutant potential of a waste with a view to reusing it,
      it is difficult to conclude on the environmental soundness of such a practice.
      Further experiments are necessary to investigate the environmental impact of TFA
      introduced in cement-based mortars depending on the reuse scenario.

PMID- 17182182
TI  - Getting a handle on process and change in CBT for chronic pain.

PMID- 17182181
TI  - Age-dependent loss of NGF signaling in the rat basal forebrain is due to
      disrupted MAPK activation.
AB  - The loss of nerve growth factor (NGF) and its high affinity receptor TrkA has
      been implicated in the loss of cholinergic tone and function in Alzheimer's
      disease (AD) and normal aging. We employed an animal model of aging, the aged
      rat, which also exhibits memory loss and NGF alterations. Basal forebrain TrkA
      levels increased after injection of NGF in the hippocampus within 1h in young
      rats, but this response was diminished in aged animals as determined by Western
      blot analysis. Further, NGF activated MAPK pathways without changing total ERK
      levels and the activation of these pathways was also diminished in aged animals.
      The exogenous NGF injection did not appear to activate the PI-3K pathway or alter
      total levels of Akt significantly. These data shed light on mechanisms of NGF
      signaling in the CNS, and alterations in this signaling cascade associated with
      age and memory loss. These findings might lead to development of novel treatment
      therapies for the memory loss associated with AD and other age-associated
      neurodegenerative diseases.

PMID- 17182183
TI  - Morphine, nortriptyline and their combination vs. placebo in patients with
      chronic lumbar root pain.
AB  - Although lumbar radicular pain is the most common chronic neuropathic pain
      syndrome, there have been few randomized studies of drug treatments. We compared
      the efficacy of morphine (15-90 mg), nortriptyline (25-100 mg), their
      combination, and a benztropine "active placebo" (0.25-1 mg) in patients with
      chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of
      maintenance at the highest tolerated doses, and 2 weeks of dose tapering. The
      primary outcome was the mean daily leg pain score on a 0-10 scale during the
      maintenance period. Secondary outcomes included a 6-point ordinal global pain
      relief scale, the Beck Depression Inventory (BDI), the Oswestry Back Pain
      Disability Index (ODI) and the SF-36. In the 28 out of 61 patients who completed
      the study, none of the treatments produced significant reductions in average leg
      pain or other leg or back pain scores. Pain reduction, relative to placebo
      treatment was, 14% for nortriptyline (95% CI=[-2%, 30%]), 7% for morphine (95%
      CI=[-8%, 22%]), and 7% for the combination treatment (95% CI=[-4%, 18%]). Mean
      doses were: nortriptyline alone, 84+/-24.44 (SD) mg/day; morphine alone, 62+/-29
      mg/day; and combination, morphine, 49+/-27 mg/day plus nortriptyline, 55 mg+/
      33.18 mg/day. Over half of the study completers reported some adverse effect with
      morphine, nortriptyline or their combination. Within the limitations of the
      modest sample size and high dropout rate, these results suggest that
      nortriptyline, morphine and their combination may have limited effectiveness in
      the treatment of chronic sciatica.

PMID- 17182186
TI  - Using screening tools to identify neuropathic pain.

PMID- 17182184
TI  - Mortality from opioid analgesics must not be ignored.

PMID- 17182187
TI  - Progesterone supplementation during mid-gestation increases the risk of abortion
      in Neospora-infected dairy cows with high antibody titres.
AB  - Progesterone has been reported to reduce Th1 responses during pregnancy. Thus,
      given that an excessive Th1 response could lead to abortion in Neospora-infected
      dairy cows, we hypothesized a reduction in abortion risk following progesterone
      supplementation during the mid-gestation period in these animals. Seropositive
      animals were assigned on day 120 of gestation to a Control (n=33) or Treatment
      (n=34) group. Treatment consisted of progesterone supplementation by fitting a
      progesterone releasing intravaginal device containing 1.55g of progesterone for
      28 days. Mean Neospora caninum antibody titres tested by ELISA on days 40, 90 and
      120 of gestation were used to classify the cows as showing high (> or =30 units)
      or low (<30 units) titration. Abortion rate showed a significant increase
      (P<0.01) in the Treatment group (35%) compared to the Control (9%). Using
      logistic regression procedures, there was a significant (P<0.0001) interaction
      between progesterone treatment and antibody titration. Progesterone-treated cows
      with a high antibody titre showed a likelihood of abortion 14.3 times higher than
      those not treated, while in cows with low antibody titres, exogenous progesterone
      had not effect. Our results do not support our starting hypothesis and suggest
      that progesterone supplementation in cows with high N. caninum antibody titres
      increases the risk of abortion possibly by affecting cell-mediated immune
      responses.

PMID- 17182188
TI  - Local inflammation as a possible mechanism of resistance to gastrointestinal
      nematodes in Angus heifers.
AB  - Understanding mechanisms of resistance to gastrointestinal nematodes is important
      in developing effective and sustainable control programs. A resource population
      of Angus cattle consisting of approximately 600 animals with complete pedigree
      records has been developed. The majority of these animals were completely
      characterized for their resistance to natural challenge by gastrointestinal
      nematodes. As the first step towards understanding the molecular basis of disease
      resistance, we investigated expression profiles of 17 cytokines, cytokine
      receptors, and chemokines using real-time RT-PCR in animals demonstrating
      resistance or susceptibility to pasture challenge. The animals exposed to natural
      infection for approximately 6 months were treated to remove existing parasites
      and then experimentally challenged with both Ostertagia ostertagi and Cooperia
      oncophora. The mRNA expression profiles of these genes in abomasal and mesenteric
      lymph nodes (ALN, MLN), fundic and pyloric abomasa (FA, PA), and small intestine
      (SI) were compared between resistant and susceptible animals. Resistant heifers
      exhibited elevated expression of inflammatory cytokines such as TNFalpha, IL
      1beta, and MIP-1alpha in fundic and pyloric abomasa 7 days post infection.
      Expression levels of IL-10, polymeric immunoglobullin receptor gene (PIGR), and
      WSX-1 were also 2.7-19.9-folds higher in resistant than susceptible heifers in
      these tissues. No difference in expression of CXCL6, CXCL10, IFN-gamma, IL-2, IL
      4, IL-6, IL-8, IL-12 p40, IL-13, IL-15 and IL-18 was observed between the two
      groups. The expression of MIP-1alpha, IL-6, and IL-10 was also elevated in small
      intestines in resistant animals. In contrast, little difference in expression of
      these genes was detected between resistant and susceptible groups in the draining
      lymph nodes. These data indicate that resistant animals can better maintain
      inflammatory responses at the site of infection, suggesting a possible novel
      mechanism of resistance.

PMID- 17182189
TI  - 19F NMR studies of solvent exposure and peptide binding to an SH3 domain.
AB  - (19)F NMR was used to study topological features of the SH3 domain of Fyn
      tyrosine kinase for both the free protein and a complex formed with a binding
      peptide. Metafluorinated tyrosine was biosynthetically incorporated into each of
      5 residues of the G48M mutant of the SH3 domain (i.e. residues 8, 10, 49 and 54
      in addition to a single residue in the linker region to the C-terminal
      polyhistidine tag). Distinct (19)F NMR resonances were observed and subsequently
      assigned after separately introducing single phenylalanine mutations. (19)F NMR
      chemical shifts were dependent on protein concentration above 0.6 mM, suggestive
      of dimerization via the binding site in the vicinity of the tyrosine side chains.
      (19)F NMR spectra of Fyn SH3 were also obtained as a function of concentration of
      a small peptide (2-hydroxynicotinic-NH)-Arg-Ala-Leu-Pro-Pro-Leu-Pro
      diaminopropionic acid -NH(2), known to interact with the canonical polyproline II
      (PPII) helix binding site of the SH3 domain. Based on the (19)F chemical shifts
      of Tyr8, Tyr49, and Tyr54, as a function of peptide concentration, an equilibrium
      dissociation constant of 18 +/- 4 microM was obtained. Analysis of the line
      widths suggested an average exchange rate, k(ex), associated with the peptide
      protein two-site exchange, of 5200 +/- 600 s(-1) at a peptide concentration where
      96% of the FynSH3 protein was assumed to be bound. The extent of solvent exposure
      of the fluorine labels was studied by a combination of solvent isotope shifts and
      paramagnetic effects from dissolved oxygen. Tyr54, Tyr49, Tyr10, and Tyr8, in
      addition to the Tyr on the C-terminal tag, appear to be fully exposed to the
      solvent at the metafluoro position in the absence of binding peptide. Tyr54 and,
      to some extent, Tyr10 become protected from the solvent in the peptide bound
      state, consistent with known structural data on SH3-domain peptide complexes.
      These results show the potential utility of (19)F-metafluorotyrosine to probe
      protein-protein interactions in conjunction with paramagnetic contrast agents.

PMID- 17182190
TI  - Microbiological safety and clinical efficacy of radiation sterilized amniotic
      membranes for treatment of second-degree burns.
AB  - Amniotic membranes collected from the placentae of screened donors were processed
      and sterilized by gamma irradiation at 25 kGy. The sterility assurance level
      (SAL) of gamma irradiated amniotic membranes and clinical efficacy in second
      degree burn wound healing were evaluated. Processed air-dried amniotic tissue
      from 159 batches of processing was checked for the bioburden level before
      sterilization. About 39% of the tissues had bioburden in the range of 10(1)
      10(2)/100 cm(2) and 54.8% in the range of 10(2)-10(3)/100 cm(2). Based on the
      bioburden of the processed tissue prior to sterilization and the D(10) value of
      2.3 kGy for the radiation resistant reference strain Bacillus pumilus, the
      sterility assurance level of the amniotic membranes irradiated at 25 kGy is found
      to be 10(-7) to 10(-11). The burn wound healing rate was compared between the
      radiation sterilized amniotic membranes and glycerol preserved amniotic
      membranes. Fifty patients with partial-thickness burns (up to 70% TBSA) were
      selected for the study. The scalds constituted 82% (41 patients) whereas flame
      burns accounted for 18% (9 patients). Various aspects like ease of application,
      patient comfort, development of fluid under the membrane, bacterial culture of
      drained fluid, rate of epithelialization, development of hypertrophic scars,
      keloids, unstable scars and restriction of joint movements were recorded with the
      application of gamma irradiated and glycerol preserved membranes. Radiation
      sterilized amniotic membranes had advantage over the glycerolized membranes with
      respect to the ease of application. Five patients with glycerol preserved
      membranes and four with gamma irradiated membranes developed fluid. The
      bacteriology of fluid showed Pseudomonas aeruginosa in four cases, Staphylococcus
      aureus in two cases, Escherichia coli in two cases and Acinetobacter in one case.
      The application of radiation sterilized amniotic membranes on the burn wound
      favoured epithelialization. In all the patients, membranes dessicated and
      separated in 10-14 days time leaving behind an epithelialized surface.

PMID- 17182191
TI  - Reproducibility of repeated measurements with the Kikuhime pressure sensor under
      pressure garments in burn scar treatment.
AB  - This study investigated the reproducibility of repeated measurements with the
      Kikuhime pressure sensor under two different types of pressure garments used in
      the treatment and prevention of scars after burns. Also efficiency of garments
      was assessed in clinical circumstances by assessing pressure loss and residual
      pressure after 1 month. Intra- and inter-observer reproducibility and repeated
      measurements with 1-month time lapse were examined on 55 sites in 26 subjects by
      means of intra-class correlation coefficients and standard error of measurements.
      Results showed good to excellent ICC and low SEMs in the two conditions. There
      was a significant difference in pressure after 1 month between elastic tricot and
      weft knit garments, although evolution of pressure loss after 1 month was
      similar. Concerning different locations, there was a significant difference in
      pressure loss after 1 month between gloves and sleeves with the largest pressure
      loss for sleeves. Considering these results we concluded that the Kikuhime
      pressure sensor provides valid and reliable information and can be used in
      comparative clinical trials to evaluate pressure garments used in burn scar
      treatment. Secondly, elastic tricot garments in our study tended to have higher
      clinical pressures but both types of garments had similar pressure loss over
      time.

PMID- 17182192
TI  - Pseudomyxoma peritonei.
AB  - Pseudomyxoma peritonei (PMP) is a rare condition, which is known for its high
      mortality when not treated properly. The first step to improve prognosis of these
      patients is to recognize this clinical syndrome preferably in an early stage.
      Knowledge of pathogenesis and common diagnostic tools is essential in this
      regard. Treatment strategy for PMP should pursue complete cytoreduction and
      prevention of recurrence or progression. Combined modality treatment, consisting
      of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, seems
      very efficient in this regard. This approach is currently carried out in many
      centers throughout the world with promising results and seems to win ground as
      the standard treatment approach.

PMID- 17182193
TI  - Sleep duration and smoking cessation in student nurses.
AB  - STUDY OBJECTIVES: To assess predictors of smoking cessation in young adults.
      DESIGN: Prospective study of smoking cessation. SETTING: 32 Schools of Nursing in
      Southwest Germany. PARTICIPANTS: 500 student nurses, 82% female, median age 19.9
      years, who smoked at baseline. MEASUREMENTS AND RESULTS: Smoking status and
      potential predictors of smoking cessation were assessed by two questionnaires
      within a median time interval of 13.1 months. At follow-up, 10.6% of the
      participants had stopped smoking. Sleep duration was positively associated with
      smoking cessation. One hour additional sleep per night at baseline increased the
      relative probability to stop smoking by 1.48 (95% CI 1.14-1.93). The number of
      cigarettes per day and the 'self-assessment of smoking behaviour in 5 years' were
      additional factors predicting smoking cessation. CONCLUSIONS: Sleep duration may
      influence smoking cessation and may have relevance for advising people who want
      to quit smoking.

PMID- 17182194
TI  - Psychometrics of the Drinker Inventory of Consequences (DrInC).
AB  - The Drinker Inventory of Consequences (DrInC) was developed for Project MATCH to
      assess the consequences of drinking in five domains. The present study, using
      baseline data from the 1382 participants involved in the COMBINE Study, analyzed
      the psychometrics of the 50-item DrInC and its shorter form, the 15-item SIP.
      Findings indicate the DrInC is reliable, valid, and clinically useful and that
      DrInC subscales are internally consistent and non-redundant. In an examination of
      the shorter version of the DrInC, findings suggest that the SIP is suitable when
      assessing the overall level of drinking-related consequences.

PMID- 17182195
TI  - Participation in specific treatment components predicts alcohol-specific and
      general coping skills.
AB  - This study identified which aspects of substance abuse treatment in community
      residential facilities (CRFs) were correlated with patients' post-treatment
      coping. A total of 2376 patients supplied demographic information and completed
      measures at baseline (coping and abstinence self-efficacy) and one year after
      treatment (coping, level of drug and alcohol use, and substance-related
      problems). Staff provided information about treatment orientation and patients'
      participation in treatment (e.g., life skills training, vocational counseling).
      The data were used to predict coping 1 year after treatment. As expected, higher
      levels of general approach coping and alcohol-specific coping and lower levels of
      general avoidance coping were associated with less 1-year alcohol and drug use
      and fewer drinking problems. Patients' greater level of participation in life
      skills counseling predicted more approach coping at 1 year. In addition, positive
      social relationships and participation in 12-step self-help groups predicted less
      general avoidance coping and more alcohol-specific coping at 1 year post
      treatment. Life skills training, 12-step self-help groups, and enhancement of
      supportive relationships during CRF treatment for substance abuse are related to
      healthy coping. Future research should examine the effect of these components in
      less intensive programs and with women.

PMID- 17182197
TI  - Proteomic survey of the pathogenic Mycoplasma hyopneumoniae strain 7448 and
      identification of novel post-translationally modified and antigenic proteins.
AB  - Mycoplasma hyopneumoniae is an important pathogen for pigs, being the causative
      agent of enzootic pneumonia. Recently, the genome sequences of three strains, J,
      7448 and 232 have been reported. Here, we describe the results of a proteomic
      analysis, based on two-dimensional gel electrophoresis of soluble protein
      extracts, immunoblot and mass spectrometry, which was carried out aiming the
      identification of gene products and antigenic proteins from the M. hyopneumoniae
      pathogenic strain 7448. A preliminary M. hyopneumoniae proteome map in two pH
      ranges (3-10 and 4-7) was produced. A total of 31 different coding DNA sequences
      (CDSs), including three hypothetical ones, were experimentally verified with the
      identification of the corresponding protein products by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry. According to the Clusters
      of Orthologous Groups (COG) functional classification, the identified proteins
      were assigned to the groups of metabolism (13), cellular processes (5) and
      information and storage processing (4). Nine of the identified proteins were not
      classifiable by COG, including some related to cytoadherence and possibly
      involved in pathogenicity. Moreover, at least five highly antigenic proteins of
      M. hyopneumoniae were identified by immunoblots, including four novel ones (a
      heat shock protein 70, an elongation factor Tu, a pyruvate dehydrogenase E1-beta
      subunit and the P76 membrane protein). The now available proteome map is expected
      to serve as a reference for comparative analyses between M. hyopneumoniae
      pathogenic and non-pathogenic strains, and for methabolic studies based on cells
      cultured under modified conditions.

PMID- 17182196
TI  - Efficacy of a behavioral intervention for increasing safer sex behaviors in HIV
      positive MSM methamphetamine users: results from the EDGE study.
AB  - BACKGROUND: Methamphetamine use has been associated with rising STI/HIV
      transmission rates, particularly among men who have sex with men (MSM).
      Interventions which successfully reduce risk for HIV transmission among this
      population are a public health priority. This study examined the efficacy of a
      behavioral intervention for increasing safer sex behaviors in the context of
      ongoing methamphetamine use in a sample of HIV-positive, methamphetamine-using
      MSM. METHODS: Three-hundred and forty-one participants from San Diego, CA were
      randomly assigned to receive either a safer sex behavioral intervention (EDGE) or
      a time-equivalent diet-and-exercise attention-control condition. Random effects
      regression analyses were used to evaluate change in safer sex behaviors over a 12
      month period. RESULTS: Participants in the EDGE intervention engaged in
      significantly more protected sex acts at the 8-month (p=0.034) and 12-month
      assessment (p=0.007). By 12-months post-baseline, a greater percentage of
      protected sex acts was observed for EDGE (25.8%) vs. control participants (18.7%)
      (p=0.038). There was a significant time-by-intervention interaction (p=0.018) for
      self-efficacy for condom use, suggesting that EDGE participants' self-efficacy
      demonstrated a greater increase over time compared to control participants.
      CONCLUSIONS: These results suggest that it is possible to reduce high risk sexual
      behaviors in the context of ongoing methamphetamine use among HIV-infected MSM.

PMID- 17182198
TI  - EUROTOX's view regarding the ROLE and TRAINING of certified European registered
      toxicologists (ERT).
AB  - Toxicology's evolution from a traditional science of poisons to an extensive
      discipline has introduced complications and ambiguity in the definition of a
      scientific area of qualification and training. The need to define toxicology and
      to identify and standardise the roles and the profiles of practising
      toxicologists in order to certify the professional credibility of toxicologists
      has been recognised by national registries and certifying boards across the USA,
      Europe and Asia. Established in 1994, the EUROTOX Model (www.eurotox.com) has
      promoted the harmonisation of educational differences, practical experiences and
      common visions and requirements for the accreditation of toxicologists in Europe.
      Such harmonisation should be seen as an indispensable step towards the mutual
      recognition of registered toxicologists at a global level and to promote the
      development of shared educational and training programmes on a regional basis. A
      description of typical professional roles for toxicologists with required
      educational background, training and experience are presented in this paper and
      serve as the basis for the ERT templates, a self-evaluation tool for individuals
      seeking ERT recognition.

PMID- 17182200
TI  - Acupuncture for postmenopausal hot flashes.
AB  - OBJECTIVE: To determine whether individually tailored acupuncture is an effective
      treatment option for reducing postmenopausal hot flashes and improving quality of
      life. METHODS: In a randomized, placebo-controlled pilot study, 29 postmenopausal
      participants averaging at least seven moderate to severe hot flashes per 24h,
      with a baseline estradiol concentration of less than 50 pg/mL and a normal TSH
      level, were randomized to receive 7 weeks (nine treatment sessions) of either
      active acupuncture or placebo acupuncture (placebo needles that did not penetrate
      the skin at sham acupuncture points). Participants recorded hot flashes in logs
      that were reported daily. Global indices of the severity and frequency of hot
      flashes were derived from the participants' daily logs. RESULTS: Participants
      receiving the active treatment had a greater reduction in hot flash severity
      (24.5+/-30.7%) compared to those receiving placebo (4.4+/-17.1%, P=0.042). Within
      group repeated measures analyses of variance revealed a significant reduction in
      hot flash severity in the active (P=0.042), but not in the placebo treatment
      group (P=0.15). Although there was no significant group difference in the
      reduction of hot flash frequency between the active (42.4+/-32.2%) and placebo
      groups (32.0+/-26.5%; P>or=0.352), within group repeated measures analyses of
      variance revealed that the reduction was statistically significant in both groups
      (P<or=0.001). CONCLUSIONS: Standardized, individually tailored acupuncture
      treatment was associated with significantly greater decrease in the severity, but
      not the frequency, of hot flashes, in symptomatic postmenopausal women when
      compared to placebo acupuncture of equal duration. Future, larger scale, studies
      are needed.

PMID- 17182201
TI  - Towards a correlation between drug properties and in vitro transdermal flux
      variability.
AB  - Over recent years, there has been growing evidence that the permeability
      coefficient variability describing any specific transdermal drug delivery system
      is not always normally distributed. However, since different researchers have
      used different test compounds, methodologies and skin types, it has been
      difficult to identify any general correlation between drug properties and flux
      variability. The aim of the present study was to investigate whether there was a
      relationship between these two variables. To this end, six different compounds
      (sucrose, adenosine, aldosterone, corticosterone, oestradiol and testosterone)
      exhibiting a range of partition coefficients but relatively similar molecular
      weights were screened by taking multiple replicate measurements of their
      permeation profiles as they penetrated across porcine skin in vitro. It was found
      that for relatively hydrophilic solutes (log P(o/w)< or = approximately 2.5),
      physicochemical properties that facilitated slow transdermal flux were associated
      with more positively skewed permeability coefficient distributions while rapid
      flux was associated with more symmetric distributions. However, no correlation
      could be found between molecular properties and the extent of statistical fit to
      either the normal or log-normal distribution.

PMID- 17182203
TI  - Development of a harmonised method for the profiling of amphetamines VI:
      Evaluation of methods for comparison of amphetamine.
AB  - Amphetamine samples were analysed by gas chromatography-mass spectrometry (GC
      MS), and the peak areas of 33 target compounds were transformed by applying
      various pretreatment techniques. The objective was to optimise the ability of a
      number of distance metrics to establish links between samples of amphetamine
      originating from the same batch (henceforth referred to as linked distances).
      Furthermore, partial least squares discriminant analysis (PLS-DA) was used to
      evaluate the effects of various pretreatment methods on separation of amphetamine
      batches synthesised by the Leuckart reaction, reductive amination of benzyl
      methyl ketone, and the nitrostyrene route. The most efficient way to pretreat GC
      MS data varied for the different distance metrics, although best results were
      obtained when data were normalised to the sum of peak areas, and either the
      fourth root or a logarithm was applied to the normalised data. When pretreating
      normalised data by fourth root transformation, Pearson correlation was the
      distance metric that was most successful at finding linked samples. Normalisation
      and the use of fourth root also represented the best method of pretreating data
      when employing PLS-DA to separate samples synthesised by different routes. To
      achieve a faster and more user-friendly procedure for evaluating chromatograms,
      experiments were performed in which the number of target compounds used to
      compare samples was reduced. The effect of each compound that was removed was
      studied by applying PLS-DA and by using Pearson correlation to calculate linked
      distances as well as unlinked distances (between samples from different batches
      of amphetamine). Considering both links between samples from the same batch and
      separation of samples synthesised by different routes, the best results were
      obtained with the data set comprising 26 compounds. Finally, it was found that
      the profiling method developed in this work was superior to an existing technique
      with respect to separating linked and unlinked distances.

PMID- 17182202
TI  - Ganoderma lucidum polysaccharides enhance the function of immunological effector
      cells in immunosuppressed mice.
AB  - The present study was designed to determine in vivo efficacy of Ganoderma lucidum
      polysaccharides (Gl-PS) for enhancing the activity of immunological effector
      cells in immunosuppressed mice. Mice were injected intraperitoneally (i.p.) once
      daily with low-dose (2.5mg/kg), intermediate-dose (25mg/kg), and high-dose (250
      mg/kg) of Gl-PS, respectively, for 7 consecutive days 24h after i.p. injection of
      a immunosuppressing anti-tumor agent cyclophosphamide (Cy, 300 mg/kg). In Cy
      treated mice, compared to vehicle, low-dose Gl-PS accelerated recovery of bone
      marrow cells, red blood cells and white blood cells, as well as splenic natural
      killer cells and natural killer T cells, and enhanced T and B cell proliferation
      responses on day 8, cytotoxic T lymphocyte activity on day 5, as well as NK cell
      and lymphokine activated killer cell activity on days 7-9. Furthermore, it
      promoted phagocytosis and cytotoxicity of macrophages on day 12. The above
      beneficial effects induced by the low-dose Gl-PS treatment did not result in any
      side effects. These results demonstrate the efficacious effects of low-dose Gl-PS
      treatment for enhancing the activity of immunological effector cells in
      immunosuppressed mice, and may provide a basis for applying this herb as an
      efficacious adjacent immunopotentiating therapy against cancer chemotherapy
      induced immunosuppression.

PMID- 17182204
TI  - The relationship between cerebral T2 hyperintensity and fixation suppression of
      vestibulo-ocular reflex in elderly patients with dysequilibrium symptoms.
AB  - OBJECTIVES: To evaluate the relationship between cerebral T2 hyperintensity on
      MRI and visual suppression of vestibulo-ocular reflex (VOR) in elderly patients
      with dysequilibrium symptoms. METHODS: Eighty-nine elderly patients with no MRI
      abnormalities in the infratentorial region aged 60-89 years complaining
      dysequilibrium symptoms were studied. Cases with whom a definitive diagnosis of
      peripheral or central disease could be established were not included. T2
      hyperintense lesions in the cerebrum: basal ganglia, subcortical white matter and
      periventricular white matter were evaluated. VOR in darkness and fixation
      suppressed VOR using pseudo-sinusoidal rotation stimuli were recorded to
      calculate visual suppression rate. Correlation between visual suppression rate
      and semi-quantitative scores for severity of T2 hyperintensity in the cerebrum
      was investigated. RESULTS: Patients with T2 hyperintensity in the cerebrum
      exhibited significantly lower visual suppression rate than those without lesions
      in the cerebrum. Multiple regression analysis showed that visual suppression rate
      was significantly and negatively correlated with severity of lesions in the basal
      ganglia, but not with patient age, severity of subcortical white matter lesions,
      or that of periventricular white matter lesions. CONCLUSIONS: In elderly patients
      with dizziness with a non-specific history and otoneurological findings, fixation
      suppression of vestibular nystagmus was associated with T2 hyperintensities in
      the basal ganglia.

PMID- 17182205
TI  - Woakes' syndrome and albinism.
AB  - Nasal polyposis is a very common and multifactorial disease. Whereas eosinophil
      dominated polyps often are sensitive to anti-inflammatory treatment like
      corticosteroids, the therapy of polyps without eosinophils is more difficult and
      disappointing. We report the clinical course of a 29-year-old albino patient
      suffering from a extreme manifestation of Woakes' syndrome, which is
      characterized by severe recurrent nasal polyps, often without eosinophils on
      histological examination and with broadening of the nose. In this case, the
      recurrent fibrotic polyps without eosinophils were resistant to conventional
      medical and surgical treatment and required further treatment with radiotherapy
      with awareness of all possible future sequelae. The pathoetiology and treatment
      of Woakes' syndrome as well as of albinism were discussed.

PMID- 17182206
TI  - Telomerase induction in T cells: a cure for aging and disease?
AB  - Cells of the immune system are unique among normal somatic cells in that they
      have the capacity to upregulate the telomere-extending enzyme, telomerase, albeit
      in a precisely controlled fashion. Kinetic analysis of telomerase activity in
      long-term T cell cultures has documented that the high level of telomerase
      induced in concert with activation reaches a peak at 3-5 days, then declines by 3
      weeks. The process is recapitulated during secondary antigenic stimulation, but
      by the third, and all subsequent stimulations in vitro, CD8 T cells are unable to
      upregulate telomerase. Cell division in the absence of telomerase activity
      results in progressive telomere shortening, and ultimately, the DNA damage/cell
      cycle arrest that is signaled by critically short telomeres. Cultures of
      senescent CD8 T cells show altered cytokine patterns, resistance to apoptosis,
      and absence of expression of the CD28 costimulatory receptor. CD8 T cells with
      these and other features of replicative senescence accumulate progressively with
      age, and at an accelerated rate, during chronic infection with HIV-1. Clinical
      studies have shown that high proportions of CD8 T cells with the senescent
      phenotype correlate with several deleterious physiologic outcomes, including poor
      vaccine responses, bone loss, and increased proinflammatory cytokines.
      CD8(+)CD28(-) T cells have also been shown to exert suppressive activity on other
      immune cells. Based on the central role of telomere shortening in the replicative
      senescence program, we are developing several telomerase-based approaches as
      potential immunoenhancing treatments for aging and HIV disease. Gene therapy of
      HIV-specific CD8 T cells with the telomerase catalytic component (hTERT) results
      in enhanced proliferative capacity, increased anti-viral functions, and a delay
      in the loss of CD28 expression, with no changes in karyotype or growth kinetics.
      These proof-of-principle studies have led to screening for pharmacological
      approaches that might mimic the gene therapy effects, in a more clinically
      suitable formulation.

PMID- 17182208
TI  - Addison's disease due to adrenal tuberculosis: contrast-enhanced CT features and
      clinical duration correlation.
AB  - PURPOSE: To describe CT morphology of untreated adrenal tuberculosis during the
      different stages of the natural history of the disease and to evaluate the
      diagnostic implications of CT features. MATERIALS AND METHODS: We retrospectively
      evaluated CT features in 42 patients with documented adrenal tuberculosis for the
      location, size, morphology, and enhancement patterns shown on CT images. The
      clinical duration were correlated with the CT features. RESULTS: Of the 42
      patients with untreated adrenal tuberculosis, bilaterally enlarged adrenal glands
      were revealed in 38 cases (91%), unilaterally enlarged in 3 cases (7%), and
      normal size in 1 case (2%). Of the 41 cases (98%) with enlargement, mass-like
      enlargement was seen in 20 cases (49%) and enlargement with preserved contours in
      21 cases (51%). Peripheral rim enhancement presented in 22 cases (52%) on
      contrast-enhanced CT. Non-enhanced CT scan revealed calcification in 21 cases
      (50%). As the duration of Addison's disease increased, the presence of
      calcification and contour preservation increased concomitantly (p<0.001), whereas
      peripheral rim enhancement and mass-like enlargement decreased concomitantly on
      CT images (p<0.001). CONCLUSION: CT may be helpful in diagnosing adrenal
      tuberculosis when clinically suspected, and CT features are correlated to the
      clinical duration of Addison's disease.

PMID- 17182209
TI  - The corner of the gastroenterologist: what colonoscopy can do, what to ask to
      radiologist.
AB  - Colonoscopy is the diagnostic technique of choice for most colonic diseases and
      allows to explore the entire colonic mucosal surface and to visualize the mucosa
      of terminal ileum. When it is done with appropriate indications, significantly
      more clinically relevant diagnoses are made. Moreover, colonoscopy keeps an
      operative role in the treatment of some acute and chronic colonic diseases and it
      is the most effective colorectal cancer screening modality. The endoscopic
      exploration of colon is not infallible and presents rare complications. Programs
      of endoscopic training and practice, monitoring of quality indicators and
      continuous technological development are improving endoscopic diagnostic and
      therapeutic role. Appropriate indications for colonoscopy, its limits and
      complications and questions for the radiologist are discussed.

PMID- 17182210
TI  - MRI in long-term evaluation of reconstructed hind-feet of land-mine trauma
      patients.
AB  - INTRODUCTION: The purpose of this study was to assess the flap reconstructed hind
      feet of patients with MRI who were traumatized by land-mine. MATERIALS AND
      METHODS: T1 and T2 weighted images were obtained in 7 patients, 12 months later
      the reconstruction of their hind feet by myocutaneous flaps after land-mine
      trauma. RESULTS: In all patients T2 signal intensities of the myocutaneous flaps
      were slightly high compared to normal undisturbed muscle. Slight vascular
      engorgement was noted in the vicinity of the flaps in all cases. There were ankle
      joint ankylose (n=1), tarsal coalition (n=3), sklerosis within the calcaneus
      (n=1), bone cortex irregularities (n=3), absence of calcaneus (n=4), deformity in
      talus and bone marrow edema (n=1), navicular edema (n=2), remodeling in the
      superior aspect of talus neck (n=2), absence of talus (n=2), talocalcaneal
      ankylose (n=1), small collection in the superior aspect of flap (n=1), drenage
      canules (n=1). CONCLUSION: In reconstructed hind feet by myocutaneus flaps done
      for land-mine traumas, MRI presents useful information by displaying detailed
      anatomy of the flaps, bones, joints, soft tissues and associated complications.

PMID- 17182207
TI  - Dendritic cells in human aging.
AB  - Dendritic cells (DCs) play a critical role in linking innate and adaptive
      immunity. A role of DCs in immunosenescence and chronic inflammation associated
      with aging has not been investigated in detail. In this article, we will briefly
      review DCs biology and changes associated with human aging.

PMID- 17182211
TI  - Determination of reduced and oxidized glutathione in biological samples using
      liquid chromatography with fluorimetric detection.
AB  - A HPLC method for determination of both reduced (GSH) and oxidized (GSSG)
      glutathione in plasma, whole blood and rat hepatocytes has been developed and
      evaluated. Reduced glutathione reacts with orthophthaldehyde (OPA) to form a
      stable, highly fluorescent tricyclic derivate at pH 8, while GSSG reacts with OPA
      at pH 12. At measurement of GSSG, GSH was complexed to N-ethylmaleimide. For the
      separation, reverse phase column Discovery C(18), 150 mm x 4 mm, 5 microm, was
      used. The mixture of methanol and 25 mM sodium hydrogenphosphate (15:85, v/v), pH
      6.0, was used as mobile phase. The analytical performance of this method is
      satisfactory for both GSH and GSSG. The intra-assay coefficients of variation
      were 1.8 and 2.1% for whole blood, 2.0 and 1.9% for rat hepatocytes, 4.3 and 5.2%
      for plasma. The inter-assay coefficients of variation were 5.8 and 6.2% for whole
      blood, 6.6 and 7.1% for rat hepatocytes, 6.9 and 7.8% for plasma. The recoveries
      were as follows: 98.2% (CV 3.5%) and 101.5% (CV 4.2%) for whole blood, 99.1%
      (2.5%) and 102.3 (4.4%) for rat hepatocytes, 94.1% (CV 7.5%) and 103.5 (CV 8.5%)
      for plasma. The calibration curve was linear in the whole range tested. The limit
      of detection was 14.0 and 5.6 fmol, respectively. The preliminary reference
      ranges of reduced and oxidized glutathione in a group of blood donors are (4.69+/
      0.93) and (0.28+/-0.12)micromol/gHb for whole blood, (1.82+/-0.55) and (0.154+/
      0.044)microM for plasma.

PMID- 17182212
TI  - [Traumatic brain injury and asymmetry in pupillary size in severe head injury at
      the initial state: aetiology and value of the mydriasis].

PMID- 17182213
TI  - [Anaesthesia for Kartagener's syndrome].

PMID- 17182214
TI  - The Personality Assessment Inventory in individuals with traumatic brain injury.
AB  - This study examined the Personality Assessment Inventory (PAI) in 95 individuals
      who had suffered a traumatic brain injury (TBI). Participants were recruited from
      a rehabilitation hospital (n=60) and a military hospital (n=35); despite
      differences in demographics and injury characteristics groups did not differ on
      any of the clinical scales and were thus combined. In the combined group, the
      highest mean clinical scale elevations were on Somatic Complaints, Depression,
      and Borderline Features and the most common configural profiles, based on cluster
      analysis, were Cluster 1 (no prominent elevations), Cluster 6 (social isolation
      and confused thinking), and Cluster 2 (depression and withdrawal). Factor
      analysis indicated a robust three-factor solution that accounted for 74.86
      percent of the variance and was similar to findings from the psychiatric and non
      psychiatric populations in the standardization sample. The above findings are
      compared with the previous literature on psychopathology in TBI, particularly in
      regards to the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), as well as
      previous psychometric research on the PAI.

PMID- 17182215
TI  - The contamination levels of organochlorines and the pattern of gene expressions
      in human umbilical cords from intra-pairs of twins at delivery.
AB  - In this study, we examined the contamination levels of organochlorines and the
      patterns of gene expressions using umbilical cords of twins. The contamination
      levels of total PCBs, HCB and HCHs of intra-pair of twins were close to each
      other, but that of DDTs were not so as the others. It shows that the placental or
      fetal factor may influence the transfer or the accumulation of DDTs. The patterns
      of gene expressions of intra-pair of twins were similar to each other. It may
      because the environmental factor (sharing same mother), genetic factor or the
      both of twins are similar. This study gave us some information to understand the
      fetal exposure to organochlorines. Moreover, it showed the possibility that the
      pattern of gene expression in umbilical cord reflected the intra-uterine
      environment. However, the information from general pattern of the gene expression
      is limited. Therefore, further investigation is necessary to find new markers not
      only mRNA but also protein to estimate the effects of fetal exposure of multiple
      organochlorines.

PMID- 17182216
TI  - Adolescent fluoxetine exposure produces enduring, sex-specific alterations of
      visual discrimination and attention in rats.
AB  - Over the past two decades the use of selective serotonin reuptake inhibitors
      (SSRIs) to treat behavioral disorders in children has grown rapidly, despite
      little evidence regarding the safety and efficacy of these drugs for use in
      children. Utilizing a rat model, this study investigated whether post-weaning
      exposure to a prototype SSRI, fluoxetine (FLX), influenced performance on visual
      tasks designed to measure discrimination learning, sustained attention,
      inhibitory control, and reaction time. Additionally, sex differences in response
      to varying doses of fluoxetine were examined. In Experiment 1, female rats were
      administered (P.O.) fluoxetine (10 mg/kg ) or vehicle (apple juice) from PND 25
      thru PND 49. After a 14 day washout period, subjects were trained to perform a
      simultaneous visual discrimination task. Subjects were then tested for 20
      sessions on a visual attention task that consisted of varied stimulus delays (0,
      3, 6, or 9 s) and cue durations (200, 400, or 700 ms). In Experiment 2, both male
      and female Long-Evans rats (24 F, 24 M) were administered fluoxetine (0, 5, 10,
      or 15 mg/kg) then tested in the same visual tasks used in Experiment 1, with the
      addition of open-field and elevated plus-maze testing. Few FLX-related
      differences were seen in the visual discrimination, open field, or plus-maze
      tasks. However, results from the visual attention task indicated a dose-dependent
      reduction in the performance of fluoxetine-treated males, whereas fluoxetine
      treated females tended to improve over baseline. These findings indicate that
      enduring, behaviorally-relevant alterations of the CNS can occur following
      pharmacological manipulation of the serotonin system during postnatal
      development.

PMID- 17182217
TI  - Chromatic aberration and the roles of double-opponent and color-luminance neurons
      in color vision.
AB  - How does the visual cortex encode color? I summarize a theory in which cortical
      double-opponent color neurons perform a role in color constancy and a
      complementary set of color-luminance neurons function to selectively correct for
      color fringes induced by chromatic aberration in the eye. The theory may help to
      resolve an ongoing debate concerning the functional properties of cortical
      receptive fields involved in color coding.

PMID- 17182218
TI  - The neuroanatomical basis of affective mentalizing in schizophrenia: comparison
      of patients with schizophrenia and patients with localized prefrontal lesions.
AB  - Patients with schizophrenia show impaired emotional and social behavior, such as
      misinterpretation of social situations and lack of Theory of Mind (ToM). However,
      the neuroanatomical basis of impaired ToM and its nature in schizophrenia is
      still largely unknown. Based on previous findings, the present study suggests
      that impaired social cognition observed in schizophrenic patients may be similar
      to that observed in patients with prefrontal (PFC) damage due to impaired
      'affective ToM' abilities, rather than to a general impairment in ToM. We
      examined the behavioral and neural mechanisms that underlie the social and
      communicative impairments observed in patients with schizophrenia and with PFC
      damage, by looking at differential patterns of ToM impairment in these
      individuals. The performance of 24 patients with schizophrenia was compared to
      the responses of patients with localized lesions in the ventromedial (VM) or
      dorsolateral PFC, patients with non-frontal lesions, and healthy control
      subjects. Patients with schizophrenia and those with VM lesions were impaired on
      'affective ToM' tasks but not in cognitive ToM conditions. It was concluded that
      the pattern of mentalizing impairments in schizophrenia resembled those seen in
      patients with lesions of the frontal lobe, particularly with VM damage, providing
      support for the notion of a disturbance of the fronto-limbic circuits in
      schizophrenia.

PMID- 17182220
TI  - Cytokine modulation of retinoic acid-inducible gene-I (RIG-I) expression in human
      epidermal keratinocytes.
AB  - BACKGROUND: Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH/D box
      family proteins and designated as a putative RNA helicase, which plays various
      roles in gene expression and cellular functions in response to a variety of RNA
      viruses. OBJECTIVE: The present study was designed to investigate the effects of
      interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha on RIG-I expression
      in human keratinocytes, and the expression of RIG-I in skin lesions of psoriasis
      vulgaris, in which IFN-gamma and TNF-alpha are considered to be involved in its
      pathogenesis. METHODS: The mRNA and protein expression of RIG-I was analyzed by
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.
      Immunohistochemical staining of RIG-I was examined on psoriatic skin section.
      RESULTS: The levels of RIG-I mRNA and protein were upregulated in HaCaT
      keratinocytes in the presence of IFN-gamma or TNF-alpha. Immunohistochemically,
      RIG-I was detected in the cytoplasm of the spinous and basal layers of psoriatic
      skin. CONCLUSION: Our results suggest that RIG-I might operate not only as a RNA
      helicase but also as a mediator of the cytokine network in the inflammatory skin
      diseases, such as psoriasis vulgaris.

PMID- 17182219
TI  - Homocysteine: an activity marker in Behcet's disease?
AB  - BACKGROUND: Behcet's disease (BD) is a chronic multisystem inflammatory disorder
      commonly complicated by vascular thrombosis. OBJECTIVE: In this study, we
      investigated whether hyperhomocysteinaemia, being a well known risk factor for
      atherothrombogenesis, is also a contributive risk factor for the pathogenesis and
      the activation of Behcet's disease. METHODS: Sixty-four patients fulfilling the
      criteria of the International Study Group for Behcet's disease (48 males, 16
      females, 33+/-8 years) were enrolled. They were separated into two groups with
      respect to activation features of Behcet's disease. Additionally, we collected
      the blood samples from 13 patients with BD in both active stage and in inactive
      stage. Twenty-six healthy individuals were included as a negative control group.
      Serum total homocysteine (Hcy) levels were determined by chemiluminescence
      immunoassay. RESULTS: Mean serum homocysteine concentrations in total BD patients
      were significantly higher than in the healthy controls (11.7+/-4.6 versus 8.7+/
      2.8micromol/L, p<0.01). Mean serum homocysteine concentrations in the active
      patients were significantly higher than in the inactive patients and the healthy
      controls (13.3+/-3.6; 10.8+/-5.0; 8.7+/-2.8micromol/L, respectively) (p<0.05 and
      p<0.001, respectively). There was no significant difference between the patients
      with inactive disease and the healthy controls. When the active and the inactive
      stage of 13 patients with BD were compared, we found that mean serum total
      homocysteine levels were higher in the active stage than in the inactive stage
      (p<0.05). CONCLUSION: Hyperhomocysteinaemia may be responsible for the
      endothelial damage in BD and assumed to be a risk factor and a marker for
      activation of BD.

PMID- 17182221
TI  - Psychiatric commitment: over 50 years of case law from the European Court of
      Human Rights.
AB  - PURPOSE: To extensively review the European Court of Human Rights (ECHR) case law
      concerning psychiatric commitment, and to estimate the role of this supranational
      jurisprudence in the practice of contemporary psychiatry. METHOD: Using keywords
      to search the ECHR computerised database "HUDOC", we reviewed all cases
      concerning psychiatric commitment registered between September 1953 and December
      31, 2004. Four groups were identified: applications declared inadmissible;
      applications accepted but not judged by the Court; pending cases; and cases
      judged by the Court. RESULTS: Of the almost 118,000 decisions taken by the ECHR
      in this time frame, we found 108 situations concerning psychiatric commitment. 41
      of these applications were considered by the Court to be inadmissible. 24 other
      cases were considered admissible but not judged by the ECHR. Three admissible
      cases were still pending at the end of 2004. The ECHR judged 40 cases, and found
      in 35 of them that one or several rights as guaranteed by the Convention had been
      violated. DISCUSSION: The ECHR protects the human rights of persons subjected to
      involuntary psychiatric commitment by creating supranational law in the following
      areas: definition of "unsoundness of mind"; conditions of lawfulness of
      detention; right to a review of detention by a Court; right to information; right
      to respect for private and family life; and conditions of confinement, which
      address inhuman and degrading treatment. The respective number of applications
      submitted to the ECHR did not depend on when the Convention had entered into
      force in that country. CONCLUSION: The possibility of an individual to access the
      ECHR depends on the degree of democracy in his country and on the access to legal
      assistance through non-governmental organisations or individual intervening
      parties.

PMID- 17182222
TI  - One-year outcome of low-intensity booster sessions versus care as usual in
      psychosis patients after a short-term psychoeducational intervention.
AB  - OBJECTIVE: In this study we aimed to evaluate long-term effects of a community
      based, quality of life oriented psychoeducational intervention for schizophrenia
      with and without booster sessions. METHOD: One hundred and three outpatients with
      a diagnosis of schizophrenia or schizoaffective disorder completed a 9-week
      psychoeducational programme. At the end of the programme groups were block
      randomised to either an extension programme comprising monthly booster sessions
      for a further nine months (booster condition) or routine clinical care with no
      further group meetings (non-booster condition). Outcome measures were applied
      before and after the seminar and at 6 and 12 months. RESULTS: Positive effects
      were observed after the short-term 9-week programme with regard to symptoms,
      knowledge about the illness, illness concept, control convictions and quality of
      life. These effects were retained over the 12-month period in both conditions.
      The only relevant difference between the booster and the non-booster conditions
      concerned external control convictions. CONCLUSION: Overall this 9-week programme
      has shown encouraging effects still present at 12 months after baseline
      independent of booster or non-booster conditions. Further studies are needed to
      explore whether a subgroup of patients, those with impaired neurocognitive and
      social functioning, can benefit significantly from booster sessions.

PMID- 17182224
TI  - The dysregulation of the cell cycle and the diagnosis of Alzheimer's disease.
AB  - The 'silent epidemic' of Alzheimer's disease is becoming a considerable social
      and economical problem in the developed countries. Especially so, because we
      still cannot diagnose the disease early enough, and there is no disease-modifying
      treatment. At present the only available therapeutic option is the use of
      cholinesterase inhibitors, which have mainly symptomatic short-term benefit for
      around one third of the patients. The solution to the problem would be the
      evidence-based design of early therapies, which could reverse/halt the cellular
      mechanisms that precede the formation of the typical brain pathology. The
      development of new therapeutic strategies, however, is hindered by limited
      knowledge of the pathogenic mechanisms that lead to the development of the
      sporadic form of the disease. Additionally, by the time the disease can be
      diagnosed, using the currently available diagnostic protocols, the pathology has
      spread to large areas of the brain, causing irreversible damage and functional
      disability. It is imperative therefore that we find early biomarkers for sporadic
      Alzheimer's disease, which could identify patients before substantial pathology
      develops.

PMID- 17182223
TI  - Effect of chronic citalopram on serotonin-related and stress-regulated genes in
      the dorsal raphe nucleus of the rat.
AB  - Using a model of depression in which chronic social stress induces depressive
      like symptoms, we investigated effects of the selective serotonin-reuptake
      inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of
      male rats. Expression of tryptophan hydroxylase (TPH) protein was found to be
      upregulated by the stress and normalized by citalopram, while mRNAs for genes TPH
      1 and 2 were differentially affected. Citalopram had no effect on serotonin
      transporter mRNA but reduced serotonin-1A autoreceptor mRNA in stressed animals.
      The SSRI prevented the stress-induced upregulation of mRNA for CREB binding
      protein, synaptic vesicle glycoprotein 2b and the glial N-myc downstream
      regulated gene 2, but increased mRNA for neuron-specific enolase (NSE) in both
      stressed and unstressed animals having no effect on stress-induced upregulation
      of NSE protein. These findings demonstrate that in the dorsal raphe nucleus of
      chronically stressed rats, citalopram normalizes TPH expression and blocks stress
      effects on distinct genes related to neurotransmitter release and
      neuroplasticity.

PMID- 17182225
TI  - Expecting unpleasant stimuli--an fMRI study.
AB  - Expecting forthcoming events and preparing adequate responses are important
      cognitive functions that help the individual to deal with the environment. The
      emotional valence of an event is decisive for the resulting action. Revealing the
      underlying mechanisms may help to understand the dysfunctional information
      processing in depression and anxiety that are associated with negative
      expectation of the future. We were interested in selective brain activity during
      the expectation of unpleasant visual stimuli. Twelve healthy female subjects were
      biased to expect and then perceive emotionally unpleasant, pleasant or neutral
      stimuli during functional magnetic resonance imaging. Expecting unpleasant
      stimuli relative to expecting pleasant and neutral stimuli resulted in activation
      of mainly cingulate cortex, insula, prefrontal areas, thalamus, hypothalamus and
      striatum. While certain areas were also active during subsequent presentation of
      the emotional stimuli, distinct regions of the anterior cingulate gyrus and the
      thalamus were solely active during expectation of the unpleasant stimuli. The
      identified areas may reflect a network for internal adaptation and preparation
      processes in order to react adequately to expected unpleasant events. They are
      known as well to be altered in depression. Disorders of this network may be
      relevant for psychiatric disorders such as depression.

PMID- 17182226
TI  - Amygdala reactivity predicts automatic negative evaluations for facial emotions.
AB  - The amygdala is a key structure in a limbic circuit involved in the rapid and
      unconscious processing of facial emotions. In the present study, the role of the
      amygdala in automatic, involuntary appraisal processes, which are believed to be
      a crucial component of emotion processing, was investigated in 23 healthy
      subjects. Amygdala activity was recorded in response to masked displays of angry,
      sad, and happy facial expressions using functional magnetic resonance imaging
      (fMRI). In a subsequent experiment, the subjects performed a masked affective
      priming task that characterizes automatic emotion processing by investigating the
      biasing effect of subliminally presented emotional faces on evaluative ratings to
      subsequently presented neutral stimuli. In the affective priming task,
      significant valence-congruent evaluation manipulation was observed. Subjects
      rated neutral targets more positively if they were primed by happy faces.
      Significant correlations were found between amygdala responses to masked negative
      facial expressions and negative evaluation shifts elicited by the corresponding
      emotion quality in the affective priming task. Spontaneous amygdala reactivity to
      facial emotions appears to be a determinant of automatic negative evaluative
      response tendencies. This finding might shed some light on how amygdala
      hyperresponsivity contributes to negative cognitive biases commonly observed in
      affective disorders.

PMID- 17182227
TI  - A mycelium with polyelectrolyte complex-bunched hyphae: preparation and
      fermentation performance.
AB  - We studied the immobilization of a mycelium (Aspergillus niger) using the working
      hypothesis as follows: (a) when polycation was added to the cell suspension, a
      few parts of it would bind on the surface of a hypha, allowing to gather the
      hyphae in part but not all; (b) upon further addition of polyanion, such a
      gathering of the hyphae is tightly bunched by the polyelectrolyte complex (PEC)
      which is resulted from the remaining polycation; (c) as a result, a mycelium with
      partially bunched hyphae can be obtained. Potassium poly(vinyl alcohol) sulfate
      and trimethylammonium glycol chitosan iodide [6-O-(2-hydroxyethyl-2
      (trimethylamonio)-chitosan iodide) were used as the polyanion and the polycation,
      respectively. The optical and electron microscopic analyses showed that our
      immobilized cell contains many of PEC-bunched hyphae. The sedimentation rate
      increased with the weight ratio of PEC to dry cells and leveled off at the weight
      ratio larger than 0.5. The gluconic acid production from glucose was studied by a
      semi-large scale (1l) cultivation of the imobilized and free cells using a jar
      fermentor. It was found that an apparent specific activity of the immobilized
      cells for glucose oxidation becomes 1.44 times that of the free cells even at a
      high cell density of 40 g/l.

PMID- 17182228
TI  - [Epidemiological characteristics of children less than 15 years hospitalized at
      the children hospital of Bordeaux for the diagnosis and initial treatment of type
      1 diabetes].

PMID- 17182229
TI  - [Pyoderma gangrenosum in a child with sickle cell disease].

PMID- 17182230
TI  - Synthesis, characterization and in vitro cytotoxicity studies of a macromolecular
      conjugate of paclitaxel bearing oxytocin as targeting moiety.
AB  - The present study describes the experimental synthetic procedure and the
      characterization of a new polyaspartamide macromolecular prodrug of paclitaxel,
      bearing oxytocin residues as targeting moieties. In vitro stability studies of
      bioconjugate, performed in media mimicking biological fluids (buffer solutions at
      pH 7.4 and 5.5) and in human plasma, evidenced the high stability of the
      targeting portion (oxytocin)-polymer linkage and the ability of this conjugate to
      release linked paclitaxel in a prolonged way in plasma. Moreover, preliminary in
      vitro antiproliferative studies, carried out on MCF-7 cells, that are oxytocin
      receptor positive cells, showed that the polymeric conjugate has the same cell
      growing inhibition ability of free drug.

PMID- 17182231
TI  - Solid molecular dispersions of poorly water-soluble drugs in poly(2-hydroxyethyl
      methacrylate) hydrogels.
AB  - The applicability of cross-linked hydrogels in forming solid molecular
      dispersions to enhance the delivery of poorly soluble drugs has not been fully
      explored. The purpose of this study is to characterize physicochemical parameters
      affecting the formation of solid molecular dispersions of poorly water-soluble
      drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels and to investigate
      the effect of storage humidity levels on their physical stability. Samples were
      prepared by an equilibrium solvent loading process, using diclofenac sodium,
      piroxicam and naproxen as model drugs. These were characterized by X-ray
      diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transform
      infrared spectroscopy (FTIR), as well as changes in the physical state during
      storage under different humidity conditions. The results show that a threshold
      drug loading level of about 30% exists in these solid molecular dispersions,
      above which amorphous to crystalline transition may occur. At any given drug
      loading, the onset of such change in physical state is accelerated at higher
      relative humidity levels during storage. The presence of hydrogen bonding between
      the polymer and the drug, as reflected in the observed FTIR band shifts, improves
      the compatibility between the drug and the polymer. This, together with a
      decreased mobility in the glassy polymer, helps to retard the crystallization
      event below the loading threshold. An increase in dissolution rate is also
      observed from the polymeric solid molecular dispersion as compared with that of
      the crystalline pure drug. These physicochemical results indicate that solid
      molecular dispersions based on PHEMA hydrogels can effectively enhance the
      dissolution and therefore should be potentially useful in improving the oral
      bioavailability of poorly water-soluble drugs.

PMID- 17182232
TI  - Synthesis and properties of N-nicotinoyl-2-(5-fluorouracil-1-yl)-D,L-glycine
      ester as a prodrug of 5-fluorouracil for rectal administration.
AB  - N-Nicotinoyl-2-(5-fluorouracil-1-yl)-D,L-glycine (NFG) methyl-(NFGM), ethyl
      (NFGE) and isopropyl esters (NFGIp) were synthesized and their potential as a
      prodrug of 5-fluorouracil (5-FU) for rectal administration was investigated.
      Chemical conversion proceeded either by elimination of (5-FU) or by hydrolysis of
      ester group. 5-FU was released from NFGIp, NFGE and NFGM 90.5%, 71.3% and 48.5%
      of the dose, respectively, in 80% human plasma and 79.8%, 56.3% and 31.6%,
      respectively, in pH 7.4 buffer solution after 48 h of incubation at 37 degrees C.
      Release of 5-FU occurred mainly from NFG esters but very slightly from NFG, which
      suggested that release of 5-FU was greatly dependent on the stability of the
      ester group against hydrolysis. Solubility (M) in pH 7.4 buffer solution was
      0.13, 0.09 and 0.04 and apparent partition coefficient in 1-octanol/pH 7.4 buffer
      solution was 0.76, 1.61 and 4.2, respectively, for NFGM, NFGE and NFGIp, which
      were in the ranges suitable for rectal absorption. Plasma concentration
      (microg/mL) of NFGM, NFGE and NFGIp at 50 min after rectal administration to rats
      was 1.9, 4.6 and 6.7, respectively, and that for 5-FU was below the limit of
      detection. Their potential as prodrugs of 5-FU for rectal administration is
      suggested.

PMID- 17182233
TI  - In vitro and in vivo evaluation of the transdermal iontophoretic delivery of
      sumatriptan succinate.
AB  - The objective was to evaluate the transdermal delivery of the 5-HT(1B/1D)
      agonist, sumatriptan from an iontophoretic patch system, in vivo. Initial in
      vitro experiments were conducted to optimize formulation parameters prior to
      iontophoretic delivery in Yorkshire swine. It was found in vitro that increasing
      drug load in the patch from 9.7 to 39 mg had no statistically significant effect
      on cumulative delivery (cf. 305.6+/-172.4 vs. 389.4+/-80.4 microg cm(-2),
      respectively). However, for a given drug load (39 mg) increasing formulation pH
      from pH 4.7 to 6.8 significantly increased the cumulative amount of sumatriptan
      delivered across the skin (389.4+/-80.4 vs. 652.4+/-94.2 microg cm(-2)). A
      biphasic current profile comprising intensities of 1.8 mA from t=0 to t=180 min
      and 0.8 mA from t=181 min to t=360 min was used for the in vivo experiments. Drug
      levels in the blood were 13.7+/-4.5 and 53.6+/-10.2 ng ml(-1) at the 30 and 60
      min time-points, rising to 90-100 ng ml(-1) during the 90-180 min time-period.
      The in vivo results show that the pharmacokinetics following transdermal
      iontophoretic delivery are comparable to those after oral, nasal or rectal
      administration, but do not match those upon subcutaneous injection.

PMID- 17182235
TI  - The role of hind limb flexor muscles during swimming in the toad, Bufo marinus.
AB  - Most work examining muscle function during anuran locomotion has focused largely
      on the roles of major hind limb extensors during jumping and swimming.
      Nevertheless, the recovery phase of anuran locomotion likely plays a critical
      role in locomotor performance, especially in the aquatic environment, where
      flexing limbs can increase drag on the swimming animal. In this study, I use
      kinematic and electromyographic analyses to explore the roles of four anatomical
      flexor muscles in the hind limb of Bufo marinus during swimming: m. iliacus
      externus, a hip flexor; mm. iliofibularis and semitendinosus, knee flexors; and
      m. tibialis anticus longus, an ankle flexor. Two general questions are addressed:
      (1) What role, if any, do these flexors play during limb extension? and (2) How
      do limb flexors control limb flexion? Musculus iliacus externus exhibits a large
      burst of EMG activity early in limb extension and shows low levels of activity
      during recovery. Both m. iliofibularis and m. semitendinosus are biphasically
      active, with relatively short but intense bursts during limb extension followed
      by longer and typically weaker secondary bursts during recovery. Musculus
      tibialis anticus longus becomes active mid way through recovery and remains
      active through the start of extension in the next stroke. In conclusion, flexors
      at all three joints exhibit some activity during limb extension, indicating that
      they play a role in mediating limb movements during propulsion. Further, recovery
      is controlled by a complex pattern of flexor activation timing, but muscle
      intensities are generally lower, suggesting relatively low force requirements
      during this phase of swimming.

PMID- 17182234
TI  - Effect of poly(ethylene glycol)-block-polylactide nanoparticles on hepatic cells
      of mouse: low cytotoxicity, but efflux of the nanoparticles by ATP-binding
      cassette transporters.
AB  - The objective of this paper is to study the effects of poly(ethylene glycol)
      block-polylactide (PLA-PEG) nanoparticles on hepatic cells of mouse. Blank PLA
      PEG nanoparticles have been successfully prepared and MTT assay suggested that
      the nanoparticles with HepG2 cell co-culture model did not cause significant
      changes in membrane integrity in controlled concentration range (0.001-0.1
      mg/ml). Immunohistochemical analysis demonstrated that large dose of PLA-PEG
      nanoparticles injection (42.04 mg/kg, i.v.) did not induce hepatic cell
      apoptosis. From biochemical assay experiments, although the levels of SOD
      decreased and those of MDA, NOS increased after treatment with large dose of PLA
      PEG nanoparticles injection (42.04 mg/kg, i.v.), they were all not significant
      (p>0.05). Then Kunming mice were treated with large dose of PLA-PEG nanoparticles
      (42.04 mg/kg, i.v.) and after 4 days total RNA was isolated to elucidate patterns
      of gene expression using a mouse cDNA-microarray (SuperArray). Treatment with
      nanoparticles resulted in over-expression of a lot of ATP-binding cassette (ABC)
      transporters, especially two ABC transporters (ABCA8 and ABCC5/MRP5), and down
      regulation of GSTP1, in comparison with the control. ABCA8 could extrude low
      molecular weight polymers after PLA-PEG nanoparticles hydrolysis outside the
      cells. We also discovered that ABCC5 expressed multidrug resistance protein 5
      (MRP5) to pump out conjugate (GS-X) of PLA-PEG nanoparticles with GSH. The
      results were confirmed by RT-PCR. Results of in vitro accumulation and efflux
      experiments indicated that about 51-52% (51.5% and 52.0%) intracellular PLA-PEG
      nanoparticles was expulsed after mouse primary hepatocytes reached a saturation
      uptake of nanoparticles during the concentration range of 750-1000 microg/ml. The
      results suggested that ABC transporters (especially ABCA8) pump out the polymers
      after hydrolysis from mouse hepatic cells and large dose of PLA-PEG nanoparticles
      make mouse hepatic cells gain drug resistance to PLA-PEG nanoparticles.

PMID- 17182236
TI  - Extract of Pelargonium sidoides (EPs 7630) inhibits the interactions of group A
      streptococci and host epithelia in vitro.
AB  - EPs 7630 is an extract of the root of the South African geranium Pelargonium
      sidoides. Clinical data have shown that this herbal drug preparation can be used
      to treat upper respiratory tract infections (URTI). The objective of this study
      was to investigate the impact of EPs 7630 on group A-streptococci (GAS) adhering
      to and invading host epithelial cells in vitro. Adhesion was assessed by a flow
      cytometric adhesion assay using calcein-AM-stained S. pyogenes (DSM 2071) as test
      organism, and HEp-2 cells and buccal epithelial cells (BEC) as substrata. For
      cell invasion, HEp-2 cell monolayers were infected with S. pyogenes.
      Intracellular bacteria were determined using a penicillin/gentamicin-protection
      assay. EPs 7630 was applied in therapeutically relevant concentrations between 0
      and 30 microg/ml in both test systems. Compared to controls, EPs 7630
      significantly reduced GAS adhesion to HEp-2 cells in a concentration-dependent
      manner by up to 46% (p<0.001). This was semi-quantitatively confirmed by
      fluorescence microscopy. Adhesion kinetics additionally indicated a specific
      antagonistic effect on GAS adhesion. Pre-treatment of epithelial cells or GAS
      with EPs 7630 showed that it targets GAS rather than HEp-2 cells. However when
      using BEC as substrata, GAS adhesion increased 7-fold under the influence of EPs
      7630 (p<0.001). In viability assays, HEp-2 suspension contained over 90% vital
      cells, whereas only 10% of the BEC were viable. EPs 7630 reduced GAS invasion of
      HEp-2 cells significantly when the data taken at time points 60, 120, and 180 min
      (p=0.026) were analyzed. In conclusion, EPs 7630 develops complementary anti
      infective properties: Firstly, EPs 7630 reduces bacterial adhesion to intact
      epithelial cells and thus protects the organism from bacterial colonization and
      infection/super-infection. Secondly, EPs 7630 enhances the attachment of bacteria
      to decaying BEC. In this way pathogens may be trapped and rendered inactive.
      Thirdly, the inhibition of GAS invasion of epithelial cells protects the host
      from microorganisms that may have evaded host defences and antibiotic treatment,
      and therefore prevents recurrent infections. Thus, our investigations provide a
      rational basis for the treatment of URTI with EPs 7630.

PMID- 17182237
TI  - Inhibition of lipopolysaccharid-induced sickness behavior by a dry extract from
      the roots of Pelargonium sidoides (EPs 7630) in mice.
AB  - The host response to infections comprise the synthesis and release of
      proinflammatory cytokines (e.g. IL-1ss, TNF-alpha, IL-6) which induce symptoms of
      sickness behavior characterised by anorexia, depressed activity, listlessness or
      malaise. In laboratory animals, sickness behavior can be induced by the
      administration of cytokines itself or by cytokine-inducers such as
      lipopolysaccharide (LPS), the active fragment of endotoxin from Gram-negative
      bacteria. Preparations from roots of Pelargonium sidoides have been traditionally
      used in South African folk medicine for the treatment of different diseases (e.g.
      diarrhea, dysmenorrhea, hepatic disorders and respiratory tract infections
      including tuberculosis). Today, aqueous ethanolic extracts of Pelargonium
      sidoides are marketed mainly for respiratory tract infections. We studied the
      effects of the extract EPs 7630 and different fractions separated by
      ultrafiltration in an animal model of sickness behavior. The results of this
      study demonstrate that the extract EPs 7630 and the high-molecular weight
      fraction (F3) alleviate the symptoms of sickness behavior.

PMID- 17182239
TI  - Where will large amounts of materials accumulated within the economy go?--A
      material flow analysis of construction minerals for Japan.
AB  - For all countries analyzed so far, Material Flow Analysis/Accounting (MFA)
      studies indicate that the overall stock of materials within the economy is
      growing. Most are construction minerals such as asphalt, cement, sand and gravel,
      crushed stone, and other aggregates. In the analyses described in this paper,
      flows and stocks of construction minerals were estimated for Japan from the past
      to the future to elucidate: (1) the mechanisms by which construction minerals
      become waste, and (2) the future supply of and demand for recycled crushed stone.
      The following conclusions were drawn: (1) The amounts of waste construction
      minerals generated have been and will be at much lower levels than the domestic
      demand for construction minerals. These differences might indicate consistent
      growth of the stock of construction minerals, which will become waste in the
      future. However, certain amounts of materials that we account for as stock can be
      interpreted already in the environment as dead stock or dissipated waste; such
      materials can be called "missing stock" or "dissipated stock". Capturing that
      missing or dissipated stock is very important because it provides information
      that clarifies the environmental impacts and loss of resources that these
      materials cause; it allows estimation of appropriate future waste generation. (2)
      The amount of construction minerals that are recognized as waste was estimated to
      increase in the future. An imbalance in the supply of and demand for recycled
      crushed stone will likely occur in the near future if an expected decline in
      future road construction is considered.

PMID- 17182238
TI  - Thoracoscopic talc poudrage decreases T-lymphocytes in the peripheral blood.
AB  - BACKGROUND: Thoracoscopic talc poudrage induces peripheral blood granulocytosis
      and lymphopenia. The aim of this study is to investigate the type of lymphopenia
      in patients undergoing thoracoscopic talc poudrage. METHODS: We have measured
      peripheral blood lymphocyte subsets in 11 patients undergoing thoracoscopic talc
      poudrage, before (baseline), at 24 and 48 h after the procedure. Lymphocyte
      numbers were analysed by flow cytometry for the evaluation of the CD3+, CD4+,
      CD8+ cells (total T-lymphocytes, helper T-lymphocytes, cytotoxic T-lymphocytes,
      respectively), the CD19+ cells (B-lymphocytes), and the CD16+, CD56+ and CD57+
      cells (NK-cells). No anti-inflammatory medication was permitted before, during or
      after the procedure. RESULTS: Absolute peripheral blood lymphocyte count
      significantly decreased following thoracoscopic talc poudrage compared to
      baseline values (p=0.007). Similarly, peripheral blood CD3+, CD4+ and CD8+
      lymphocyte counts significantly decreased compared to baseline (p=0.005, 0.02 and
      0.03, respectively) with a more prominent reduction of CD3/CD45RO memory cells.
      No significant difference was found in the absolute number of CD19+, CD16+,
      CD56+, and CD57+ cells before and after thoracoscopic talc poudrage. CONCLUSION:
      Patients undergoing thoracoscopic talc poudrage display peripheral blood T
      lymphopenia following the procedure.

PMID- 17182240
TI  - Interleukin-10 [ATA] promoter haplotype and prostate cancer risk: a population
      based study.
AB  - Interleukin-10 (IL-10) is a multifunctional cytokine acting as inhibitor of
      inflammatory and immune responses as well as tumour induced angiogenesis. A
      common [ATA] haplotype formed by polymorphisms at positions -1082, -819 and 
      592in the promoter of the IL-10 gene is a strong determinant for IL-10
      expression. The presence of this haplotype can be determined by analysis of the 
      592C>A polymorphism. To analyse the role of the IL-10 [ATA] haplotype in prostate
      cancer we performed a case-control study including 561 prostate cancer patients
      and 561 male, age-matched, control subjects without malignant disease. The IL-10 
      592C>A polymorphism was determined by a 5'-nuclease assay (TaqMan). IL-10 -592
      CC, CA and AA genotype frequencies were not significantly different between
      patients (53.6%, 40.0%, 6.4%) and controls (54.3%, 39.6%, 6.1%; p=0.96). IL-10
      genotypes were furthermore not associated with tumour characteristics such as
      histological grade, T stage, PSA levels at diagnosis, or age at diagnosis.
      Therefore we conclude that the IL-10 -592C>A promoter polymorphism, tagging the
      IL-10 low-producer [ATA] haplotype, is not associated with risk for prostate
      cancer.

PMID- 17182241
TI  - EORTC guidelines for the use of erythropoietic proteins in anaemic patients with
      cancer: 2006 update.
AB  - Anaemia is frequently diagnosed in patients with cancer, and may have a
      detrimental effect on quality of life (QoL). We previously conducted a systematic
      literature review (1996-2003) to produce evidence-based guidelines on the use of
      erythropoietic proteins in anaemic patients with cancer.[Bokemeyer C, Aapro MS,
      Courdi A, et al. EORTC guidelines for the use of erythropoietic proteins in
      anaemic patients with cancer. Eur J Cancer 2004;40:2201-2216.] We report here an
      update to these guidelines, including literature published through to November
      2005. The results of this updated systematic literature review have enabled us to
      refine our guidelines based on the full body of data currently available. Level I
      evidence exists for a positive impact of erythropoietic proteins on haemoglobin
      (Hb) levels when administered to patients with chemotherapy-induced anaemia or
      anaemia of chronic disease, when used to prevent cancer anaemia, and in patients
      undergoing cancer surgery. The addition of further Level I studies confirms our
      recommendation that in cancer patients receiving chemotherapy and/or
      radiotherapy, treatment with erythropoietic proteins should be initiated at a Hb
      level of 9-11 g/dL based on anaemia-related symptoms rather than a fixed Hb
      concentration. Early intervention with erythropoietic proteins may be considered
      in asymptomatic anaemic patients with Hb levels 11.9 g/dL provided that
      individual factors like intensity and expected duration of chemotherapy are
      considered. Patients whose Hb level is below 9 g/dL should primarily be evaluated
      for need of transfusions potentially followed by the application of
      erythropoietic proteins. We do not recommend the prophylactic use of
      erythropoietic proteins to prevent anaemia in patients undergoing chemotherapy or
      radiotherapy who have normal Hb levels at the start of treatment, as the
      literature has not shown a benefit with this approach. The addition of further
      supporting studies confirms our recommendation that the target Hb concentration
      following treatment with erythropoietic proteins should be 12-13 g/dL. Once this
      level is achieved, maintenance doses should be titrated individually. There is
      Level I evidence that dosing of erythropoietic proteins less frequently than
      three times per week is efficacious when used to treat chemotherapy-induced
      anaemia or prevent cancer anaemia, with studies supporting the use of epoetin
      alfa and epoetin beta weekly and darbepoetin alfa given every week or every 3
      weeks. We do not recommend the use of higher than standard initial doses of
      erythropoietic proteins with the aim of producing higher haematological
      responses, due to the limited body of evidence available. There is Level I
      evidence that, within reasonable limits of body weight, fixed doses of
      erythropoietic proteins can be used to treat patients with chemotherapy-induced
      anaemia. This analysis confirms that there are no baseline predictive factors of
      response to erythropoietic proteins that can be routinely used in clinical
      practice if functional iron deficiency or vitamin deficiency is ruled out; a low
      serum erythropoietin (EPO) level (only in haematological malignancies) appears to
      be the only predictive factor to be verified in Level I studies. Further studies
      are needed to investigate the value of hepcidin, c-reactive protein, and other
      measures as predictive factors. In these updated guidelines, we explored a new
      question of whether oral or intravenous iron supplementation increases the
      response rate to erythropoietic proteins. We found no evidence of increased
      response with the addition of oral iron supplementation, but there is Level II
      evidence of improved response to erythropoietic proteins with the addition of
      intravenous iron. However, the doses and schedules for intravenous iron
      supplementation are not yet well defined, and further studies in this area are
      warranted. The two major goals of erythropoietic protein therapy are prevention
      or elimination of transfusions and improvement of QoL. The total body of evidence
      shows that red blood cell (RBC) transfusion requirements are reduced following
      treatment with erythropoietic proteins. This analysis also confirms that QoL is
      significantly improved in patients with chemotherapy-induced anaemia and in those
      with anaemia of chronic disease following erythropoietic protein therapy, with
      more robust evidence now available that QoL was improved in studies investigating
      early intervention in cases of chemotherapy- or radiotherapy-induced anaemia.
      There is only indirect evidence that patients with chemotherapy-induced anaemia
      or anaemia of chronic disease initially classified as non-responders to standard
      doses proceed to respond to treatment following a dose increase. None of the
      studies addressed the question in a prospective, randomised fashion, and so the
      Taskforce does not recommend dose escalation as a general approach in all
      patients who are not responding. There is still insufficient data to determine
      the effect on survival following treatment with erythropoietic proteins in
      conjunction with chemotherapy or radiotherapy. Our analysis of survival endpoints
      in studies involving patients receiving radio(chemo)therapy found that most
      studies were inconclusive, with no clear link between the use of erythropoietic
      proteins and survival. Likewise, we found no clear link between erythropoietic
      therapy and other endpoints such as local tumour control, time to progression,
      and progression-free survival. There is no evidence that pure red cell aplasia
      occurs in cancer patients following treatment with erythropoietic proteins, and
      the fear of this condition developing should not lead to erythropoietic proteins
      being withheld in patients with cancer. There is Level I evidence that the risk
      of thromboembolic events and hypertension are slightly elevated in patients with
      chemotherapy-induced anaemia receiving erythropoietic proteins. Additional trials
      are warranted, especially to define the optimal doses and schedules of
      intravenous iron supplementation during erythropoietic therapy. While our review
      did not address cost benefit evaluations in detail, the consensus is that studies
      taking into account all real determinants of cost and benefit need to be
      performed prospectively.

PMID- 17182242
TI  - T-cell lymphoma of the upper eyelid: a case report and review of the literature.
AB  - We present the case report of a 95-year-old white female with a cutaneous T-cell
      lymphoma (CTCL) of the upper eyelid. Due to her comorbid medical problems,
      multidisciplinary tumor board recommendation for treatment was surgical excision.
      She underwent excision with frontalis muscle flap and contralateral eyelid full
      thickness skin graft reconstruction. The patient has been symptom free for 3.5
      years. A literature review of cutaneous CTCL isolated to the eyelid is included.

PMID- 17182243
TI  - The influence of manure composition on emissions of odour and ammonia from
      finishing pigs fed different concentrations of dietary crude protein.
AB  - An investigation was conducted into the influence of manure composition on the
      odour emission rate (OER) and the emission rate of ammonia (NH(3)), when diets
      containing 130, 160, 190 and 210gkg(-1) crude protein (CP) were fed to finishing
      pigs. A group of four boars and four gilts, housed in environmentally sealed
      pens, were assigned to each diet for a 23-day experimental period which was
      replicated three times (n=3). Ventilation air from each pen was sampled for NH(3)
      and odour, by olfactometry, on four days during the trial period. Simultaneous
      collections of manure were taken from the surface and base of each pit. The pH
      and the concentrations of dry matter, total Kjeldahl nitrogen (TKN), total
      ammoniacal nitrogen (TAN) and volatile fatty acids in the manure were measured.
      Manure composition differed between samples from the surface and base of the pit
      (P<0.05). Reducing dietary CP concentration decreased the emission of NH(3)
      (linear, P<0.001). The acetic acid:propionic acid ratio in manure samples was
      correlated to OER (r=0.79, P<0.001). There was a quadratic relationship between
      dietary CP concentration and OER (P<0.05). OER decreased between 210gkg(-1) and
      160gkg(-1) CP and increased between 160gkg(-1) and 130gkg(-1) CP. In conclusion,
      reducing dietary crude protein levels could be used effectively to reduce ammonia
      emissions and OER, although no significant advantage was to be gained in OER from
      reducing crude protein level below 160gkg(-1).

PMID- 17182244
TI  - A novel approach for medium formulation for growth of a microalga using motile
      intensity.
AB  - Motile intensity of the cells, defined as the specific mean kinetic energy, was
      measured by image analysis and used to formulate a suitable medium for the
      cultivation of a motile microalga. Nitrogen source at 60 mg/L was used as the
      target component. The cells grown in a medium containing urea showed the highest
      motile intensities during cultivation when compared to the cells grown with
      NH(4)Cl or (NH(4))(2)SO(4) as the nitrogen source. The urea culture gave the
      highest biomass yield and lipid content of 1.06+/-0.12 g/L and 22.34+/-2.56%,
      respectively after 150 h of cultivation. These results indicated a strong
      dependence of motile intensity on the nitrogen source used in the growth medium.
      This concept, which requires only a small droplet of the sample, can find
      potential application in the design and optimization of culture media.

PMID- 17182245
TI  - Characteristics of bioemulsifier V2-7 synthesized in culture media added of
      hydrocarbons: chemical composition, emulsifying activity and rheological
      properties.
AB  - The bioemulsifier V2-7 is an exopolysaccharide (EPS) synthesized by strain F2-7
      of Halomonas eurihalina and it has the property of emulsifying a wide range of
      hydrocarbons i.e. n-tetradecane, n-hexadecane, n-octane, xylene mineral light and
      heavy oils, petrol and crude oil. Characteristics of exopolysaccharide V2-7
      produced in media supplemented with various hydrocarbons (n-tetradecane, n
      hexadecane, n-octane, xylene, mineral light oil, mineral heavy oil, petrol or
      crude oil) were studied. Yield production varied from 0.54 to 1.45 g L(-1)
      according to the hydrocarbon added, in the same way chemical composition,
      viscosity and emulsifying activity of EPS varied with the culture conditions.
      Respect to chemical composition, percentage of uronic acids found in exopolymers
      produced in hydrocarbon media was always higher than that described for V2-7 EPS
      (1.32%) obtained with glucose. This large amount of uronic acid present could be
      useful in biodetoxification and waste water treatment. On the other hand, the
      highest amount of biopolymer was synthesized with mineral light oil, while the
      most active emulsifiers were those obtained from media added with petrol and n
      octane. Furthermore, all EPS were capable of emulsifying crude oil more
      efficiently than the three chemical surfactants tested as control (Tween 20,
      Tween 80 and Triton X-100). The capacity of strain F2-7 to grow and produce
      bioemulsifier in presence of oil hydrocarbons together with the high emulsifying
      activity and low viscosity power of the biopolymers synthesized in hydrocarbons
      media could be considered highly beneficial for application of both bioemulsifier
      and producing strain in bioremediation of oil pollutants.

PMID- 17182247
TI  - A tibial-based coordinate system for three-dimensional data.
AB  - An accurate and repeatable tibial measurement system will aid in the definition
      of tibial geometry and improving tibial prosthesis design. Unlike in the femur,
      there is no standardized method for constructing a tibial coordinate frame. Most
      tibial measurements are given relative to femoral axes or the coordinate frame of
      the CT/MRI scanner or radiograph machine. The objective of this study was to
      establish an independent tibial coordinate frame. Data consisted of CT scans from
      34 subjects. The tibial anatomical axis was chosen as the axial axis. The
      anteroposterior (AP) axis was selected to be parallel to the lateral surface of
      the tibial shaft and orthogonal to the anatomical axis and from this the
      mediolateral axis could be derived. The selected AP axis was compared with the
      surgical tibial AP axis by measuring their variability relative to a common axis,
      the posterior tibial condylar line (PTCL). The mean angle between the selected AP
      axis and the perpendicular to the PTCL was measured as -4.07 degrees, standard
      deviation of 4.28 degrees. The mean angle between the surgical AP axis and the
      perpendicular to the PTCL was measured as -18.56 degrees, standard deviation of
      4.66 degrees. There was no significant difference in the variance of the two sets
      of measurements (p=0.63). Variability of the selected AP axis was even smaller
      (standard deviation of 2.74 degrees) when measured independently from the PTCL
      reference axis, by aligning virtual resection profiles. Anatomically, the
      selected AP axis was almost perpendicular to the posterior tibial condylar axis.
      This coordinate system can aid in gathering consistent and repeatable
      anthropometric data that can be used to improve tibial implant design and could
      also, in combination with CT/MR imaged-based computer assisted surgery, be used
      as a guideline for tibial component positioning in TKR.

PMID- 17182248
TI  - A new CT scan method for measuring the tibial tubercle trochlear groove distance
      in patellar instability.
AB  - Patellar malalignment leading to objective or potential patella instability can
      be caused by tibial tuberosity lateralisation. This can be treated with a
      tuberosity medialisation. CT scan measurements are needed to assess the tibial
      tubercle trochlear groove distance. When using the previously described methods
      to determine this distance it can be difficult to determine the anatomical
      structures on the maximum intensity projection images, and this can lead to
      measurement error. This study was designed to compare the reliability of a new
      computer based CT measurement to the previously described method to determine the
      tibial tubercle trochlear groove distance. For each method, four observers
      measured each of 50 knees twice. The inter- and intra-observer variability for
      the conventional method and a new method were determined. Using the conventional
      method, the number of knees for which the difference between the aggregate mean
      of all eight measurements and the mean of duplicate measurements per observer
      greater than 2 mm varied among the observers between 7 and 24 for the 50 knees,
      while this variation between four and seven for the same 50 knees using the new
      method. The limits of reproducibility based on measurements from the four
      different observers improved by 25%, indicating that the measurement error is
      considerably smaller with the new method. We advise using this more accurate
      method to improve the selection of patients for a tuberosity medialisation.

PMID- 17182249
TI  - Synthesis and characterization of poly (amino ester) for slow biodegradable gene
      delivery vector.
AB  - Many therapeutic carrier materials were exploited for human gene therapy from
      viral to polymeric vectors. This research describes the evaluation of two
      biodegradable ester-bonded polymers synthesized by double-monomer
      polycondensation for a non-viral cationic polymer-based gene delivery system. The
      backbone was constructed to include inner tertiary amines and outer primary
      amines. Self-assembly with DNA resulted in the production of regularly nano-sized
      spherical polyplexes with good transfection efficiency, especially in the
      presence of serum. The polymers showed a relatively slow degradability for an
      amine-containing ester polymer, as they maintained DNA/polymer complex for 7 days
      in physiological buffer conditions. Finally, the low toxicity and slow
      degradation concluded these polymers reliable for long-term therapeutic
      applications.

PMID- 17182250
TI  - The Adamkiewicz artery: demonstration by intra-arterial computed tomographic
      angiography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of using
      multidetector-row CT angiography (CTA) with intra-arterial contrast injection (IA
      CTA) to depict the artery of Adamkiewicz (arteria radicularis magna, ARM).
      METHODS: We performed IA-CTA in 27 preoperative patients with aneurysm or
      dissection of the descending thoracic or thoracoabdominal aorta. ARM was examined
      on multiplanar and curved planar reformation images and on the paging method, and
      we investigated detectability and visualization of the ARM, the level of
      branching, and right/left frequency as well as continuity from the origin to the
      ARM. Furthermore, the bolus characteristic of contrast medium in IA-CTA was
      investigated and compared with CTA with intravenous contrast injection (IV-CTA).
      The bolus characteristic of the contrast medium was assessed by the determination
      of the CT value in the aorta in each of the 16 cases in which both IA-CTA before
      surgery and intravenous IV-CTA at the time of admission were performed. RESULTS:
      The ARMs were clearly visualized and at least one ARM to be reserved was
      determined in all patients (100%). The average number of ARM observed was 1.4+/
      0.58 per patient (39/27). Innate origin was determined in 90% (35/39) of ARMs and
      it ranged between the 8th thoracic vertebra and the 3rd lumbar vertebra levels,
      and branching from the left accounted for 63.2% (24/38). It was possible to
      observe the exact continuity from the innate origin to the ARM as well as from
      the secondary origin to the ARM mediated by collateral vesseles in 61.5% of the
      total ARMs (24/39). The CT value in the aorta calculated on IA-CTA was
      significantly higher than that on IV-CTA (p<0.05). As a result, the high bolus
      characteristic of contrast medium in IA-CTA was confirmed. CONCLUSION: It was
      possible to detect the ARM in all patients and to obtain information about the
      origin by IA-CTA. This method is considered useful for preoperative assessment of
      a descending thoracic or a thoracoabdominal aorta for aortic aneurysm or
      dissection.

PMID- 17182251
TI  - Comparing the ultrastructural effects of two different cardiac preparation- and
      perfusion-techniques in a porcine model of extracorporal long-term preservation.
AB  - OBJECTIVE: In heart transplantation a well-preserved myocardial ultrastructure is
      an important precondition for functional regeneration. Aim of the study is to
      optimize the conditions in this new established model of extracorporeal cardiac
      perfusion. METHODS: (I) In six pigs, hearts were arrested with Bretschneider
      Histidine-Tryptophan-Ketoglutarate cardioplegia and cold ischemia, explanted and
      connected to a circulating constant pressure Langendorff system (80-90mmHg) and
      perfused with leukocyte depleted autologous blood. (II) Beating hearts of seven
      pigs were explanted and connected immediately to the Langendorff system (40
      50mmHg). Myocardial biopsies (n=55) were taken in situ and during the following
      12h of reperfusion, and were prepared for electron microscopy. RESULTS:
      Cardioplegia and hypothermia (group I) induced mitochondrial edema and
      myofibrillar degeneration in cardiomyocytes and severe endothelial edema. During
      4h of reperfusion, mitochondrial edema, myofibrillar, and sarcolemmal damages in
      cardiomyocytes increased. Moderate endothelial degeneration, interstitial edema,
      and bleedings appeared. In contrast, in group II after 6h of reperfusion
      endothelia showed only mild alterations. Cardiomyocytes showed myofibrillary but
      not mitochondrial degeneration. Interstitial edema and bleedings were mild.
      CONCLUSION: Avoiding cardioplegia and hypothermia, and using lower perfusion
      pressure resulted in a better preservation of the ultrastructure in explanted
      hearts at the Langendorff system.

PMID- 17182252
TI  - Gene transfer of a soluble IL-1 type 2 receptor-Ig fusion protein improves
      cardiac allograft survival in rats.
AB  - OBJECTIVE: Interleukin-1 (IL-1) mediates ischemia-reperfusion injury and graft
      inflammation after heart transplantation. IL-1 affects target cells through two
      distinct types of transmembrane receptors, type-1 receptor (IL-1R1), which
      transduces the signal, and the non-signaling type-2 receptor (IL-1R2), which acts
      as a ligand sink that subtracts IL-1beta from IL-1R1. We analyzed the efficacy of
      adenovirus (Ad)-mediated gene transfer of a soluble IL-1R2-Ig fusion protein in
      delaying cardiac allograft rejection and the mechanisms underlying the protective
      effect. METHODS: IL-1 inhibition by IL-1R2-Ig was tested using an in vitro
      functional assay whereby endothelial cells preincubated with AdIL-1R2-Ig or
      control virus were stimulated with recombinant IL-1beta or tumor necrosis factor
      alpha (TNF-alpha), and urokinase-type plasminogen activator (u-PA) induction was
      measured by zymography. AdIL-1R2-Ig was delivered to F344 rat donor hearts ex
      vivo, which were placed in the abdominal position in LEW hosts. Intragraft
      inflammatory cell infiltrates and proinflammatory cytokine expression were
      analyzed by immunohistochemistry and real-time reverse transcriptase-polymerase
      chain reaction (RT-PCR), respectively. RESULTS: IL-1R2-Ig specifically inhibited
      IL-1beta-induced u-PA responses in vitro. IL-1R2-Ig gene transfer reduced
      intragraft monocytes/macrophages and CD4(+) cell infiltrates (p<0.05), TNF-alpha
      and transforming growth factor-beta (TGF-beta) expression (p<0.05), and prolonged
      graft survival (15.6+/-5.7 vs 10.3+/-2.5 days with control vector and 10.1+/-2.1
      days with buffer alone; p<0.01). AdIL-1R2-Ig combined with a subtherapeutic
      regimen of cyclosporin A (CsA) was superior to CsA alone (19.4+/-3.0 vs 15.9+/
      1.8 days; p<0.05). CONCLUSIONS: Soluble IL-1 type-2 receptor gene transfer
      attenuates cardiac allograft rejection in a rat model. IL-1 inhibition may be
      useful as an adjuvant therapy in heart transplantation.

PMID- 17182253
TI  - Protective effects of mycosporine-like amino acids of Synechocystis sp. PCC 6803
      and their partial characterization.
AB  - In this work, mycosporine-like amino acids (MAAs) of Synechocystis sp. PCC 6803
      were characterized and were investigated on UV induction and protective ability.
      High performance liquid chromatographic (HPLC) studies revealed three major
      compounds in the MAAs. By UV absorption and mass spectra analysis, one of the
      compounds was tentatively identified as mycosporine-tau (M-tau). One novel
      compound similar to usujirene was tentatively named as dehydroxylusujirene, and
      the other novel compound was named as M-343 according to its absorption maximum.
      In vivo experiments indicated that M-tau was induced by both UV-A and UV-B, while
      dehydroxylusujirene and M-343 were only induced by UV-A, suggesting that
      different chromophores were involved in MAAs synthesis in Synechocystis sp. PCC
      6803. It was also indicated that M-343 could be photochemically synthesized from
      some precursors. Under both UV and oxidation stresses, M-343 was more stable than
      dehydroxylusujirene and M-tau. Considering the reaction with H2O2, M-tau and
      dehydroxylusujirene might be potential antioxidants in reaction with
      physiological reactive oxygen species in vivo. In protection experiments, the
      MAAs exhibited efficient protective ability towards UV-B and H2O2 stresses, with
      maximal protection rates of 30% and 21.5%, respectively. These results indicate
      that the MAAs in Synechocystis sp. PCC 6803 act as both UV-screen and
      antioxidant.

PMID- 17182254
TI  - Isolation, purification and characterization of a DPP-III homologue from goat
      brain.
AB  - A dipeptidyl peptidase (DPP) from goat brain has been purified. The purified
      enzyme showed a single band on sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE). It is a monomer with molecular weight of 69kDa with a
      pI of 4.5. The K(m) was estimated to be 39microM for Arg-Arg-4-methoxy-beta
      naphthylamide (Arg-Arg-4mbetaNA). This enzyme is strongly inhibited by commonly
      used metallochelators and sulfhydryl reagents. Among various beta-naphthylamides
      examined, Arg-Arg-4mbetaNA was the most rapidly hydrolyzed substrate. Although,
      initially it was thought to be the DPP-III but on the basis of its molecular
      weight and inhibition studies, it was concluded that this enzyme is a functional
      homologue of DPP-III.

PMID- 17182255
TI  - Overexpression, purification and localization of apoptosis related protein from
      Plasmodium falciparum.
AB  - A growing body of evidence has ascertained that apoptosis is not only restricted
      to metazoans but also exists in unicellular parasites. In Plasmodium falciparum,
      the presence of a putative gene having sequence homology with apoptosis related
      protein (PfARP) (Gene ID PFI0450c) has raised enormous interest to unravel the
      function of this unique protein in cell death of malaria parasite. To
      characterize this protein, the PfARP gene has been amplified from the P.
      falciparum transcriptome by RT-PCR and the amplified gene has been successfully
      cloned, over-expressed and purified to homogeneity. The purified PfARP exhibits
      minimum subunit MW of approximately 24kDa as evident from SDS-PAGE. CD analysis
      reveals that the alpha and beta content of the recombinant PfARP are 61% and 15%,
      respectively. Semiquantitative RT-PCR analysis indicates the expression of PfARP
      at both metabolically less active ring and highly active trophozoite stages of
      malaria parasite. Immunofluorescence microscopy further supports that PfARP
      expresses stage specifically with the highest expression at trophozite stage and
      very little in the schizont stage. PfARP is a cytosolic protein as evident from
      immunofluorescence microscopy. The role of this protein in P. falciparum cell
      death and stage progression is not yet known. The identification, purification
      and characterization would certainly be a step to initiate work on this protein
      to evaluate its role in P. falciparum growth, multiplication and stage
      progression.

PMID- 17182256
TI  - Structural analysis of flexible proteins in solution by small angle X-ray
      scattering combined with crystallography.
AB  - In the last few years, SAXS of biological materials has been rapidly evolving and
      promises to move structural analysis to a new level. Recent innovations in SAXS
      data analysis allow ab initio shape predictions of proteins in solution.
      Furthermore, experimental scattering data can be compared to calculated
      scattering curves from the growing data base of solved structures and also
      identify aggregation and unfolded proteins. Combining SAXS results with atomic
      resolution structures enables detailed characterizations in solution of mass,
      radius, conformations, assembly, and shape changes associated with protein
      folding and functions. SAXS can efficiently reveal the spatial organization of
      protein domains, including domains missing from or disordered in known crystal
      structures, and establish cofactor or substrate-induced conformational changes.
      For flexible domains or unstructured regions that are not amenable for study by
      many other structural techniques, SAXS provides a unique technology. Here, we
      present SAXS shape predictions for PCNA that accurately predict a trimeric ring
      assembly and for a full-length DNA repair glycosylase with a large unstructured
      region. These new results in combination with illustrative published data show
      how SAXS combined with high resolution crystal structures efficiently establishes
      architectures, assemblies, conformations, and unstructured regions for proteins
      and protein complexes in solution.

PMID- 17182257
TI  - The role of rodlet cells in the inflammatory response in Phoxinus phoxinus brains
      infected with Diplostomum.
AB  - European minnows, Phoxinus phoxinus L., are commonly infected with Diplostomum
      phoxini Faust, 1918 metacercariae. A sub-sample of 34 minnows collected from the
      River Endrick, Stirlingshire, Scotland revealed that 50% of the population were
      infected (n = 17), with the cerebellum, medulla oblongata and the optic lobe
      regions of the minnow brain bearing the heaviest infections (13.7 +/- 2.6 mean +/
      S.E.; 1-38 range). Serial histological sections through the brains of both
      uninfected and infected minnows revealed the presence of rodlet cells in the
      latter, which were occasionally observed in close proximity to the tegument of a
      metacercaria. Rodlet cells were the only type of host inflammatory cells found in
      this study and their role in the host's immune response to parasitic infection is
      commented upon.

PMID- 17182258
TI  - Gamma-range corticomuscular coherence during dynamic force output.
AB  - The beta-range synchronization between cortical motor and muscular activity as
      revealed by EEG/MEG-EMG coherence has been extensively investigated for steady
      state motor output. However, there is a lack of information on the modulation of
      the corticomuscular coherence in conjunction with dynamic force output. We
      addressed this question comparing the EEG-EMG coherence and the cortical motor
      spectral power in eight healthy subjects in a visuomotor task, in which the
      subjects exerted a steady-state or periodically modulated dynamic isometric force
      output with their right-index finger to keep a visual cursor within a target
      zone. In the static condition, significant coherence was confined to the beta
      range. In the dynamic condition, the most distinct coherence occurred in the
      gamma-range and the significant beta-range coherence was strikingly reduced. The
      cortical motor power in the beta-range during dynamic force output was decreased,
      whereas the power in the gamma-range remained without significant change. We
      conclude that during dynamic force the corticospinal oscillation mode of the
      sensorimotor system shifts towards higher (principally gamma) frequencies for the
      rapid integration of the visual and somatosensory information required to produce
      the appropriate motor command.

PMID- 17182260
TI  - Analysis of neurotransmitter receptor distribution patterns in the cerebral
      cortex.
AB  - The concentration of transmitter receptors varies between different locations in
      the human cerebral cortex, but also between the different cortical layers within
      the same area. Analyzing the regional differences in the laminar distribution
      patterns of various neurotransmitter receptor binding sites by means of
      quantitative receptor autoradiography may thus provide a functionally relevant
      insight into the organization of the cortex. Here we introduce an approach to the
      analysis of in vitro receptor autoradiographic data, providing a framework for
      the assessment of differences in both mean concentration and laminar distribution
      patterns across multiple subjects. Initially, laminar receptor distribution
      patterns for cortical areas are quantified by sampling density profiles in a
      series of regions of interest (ROIs) from digitalized autoradiographs and
      computing a mean profile per ROI. These ROI mean profiles are then corrected for
      distortions in the laminar pattern introduced by cortical folding and averaged to
      yield a mean profile per area, receptor and hemisphere. Differences in mean
      binding site concentration between areas are quantified by the asymmetry
      coefficient which is the difference of the mean concentrations divided by their
      sum. To quantify differences in laminar receptor distribution patterns between
      areas, the effects of absolute binding site concentration are first removed by
      dividing each profile by its mean value. Differences in the laminar pattern were
      then quantified by calculating the Euclidean distance between these mean
      corrected profiles. For single subject analysis, we propose a permutation test,
      comparing the differences between the mean profiles for two areas to differences
      between groups of profiles randomly assembled from all ROIs sampled in either
      area. Group inference can then be based on a between-subject conjunction analysis
      after correcting p-values to control for multiple comparisons. The feasibility of
      the presented approach is demonstrated by an exemplary analysis of the
      neurochemical differences between the ventral parts of the second and the third
      visual area.

PMID- 17182259
TI  - Dodecapus: An MR-compatible system for somatosensory stimulation.
AB  - Somatotopic mapping of human body surface using fMRI is challenging. First, it is
      difficult to deliver tactile stimuli in the scanner. Second, multiple stimulators
      are often required to cover enough area of the complex-shaped body surface, such
      as the face. In this study, a computer-controlled pneumatic system was
      constructed to automatically deliver air puffs to 12 locations on the body
      surface through an MR-compatible manifold (Dodecapus) mounted on a head coil
      inside the scanner bore. The timing of each air-puff channel is completely
      programmable and this allows systematic and precise stimulation on multiple
      locations on the body surface during functional scans. Three two-condition block
      design "Localizer" paradigms were employed to localize the cortical
      representations of the face, lips, and fingers, respectively. Three "Phase
      encoded" paradigms were employed to map the detailed somatotopic organizations of
      the face, lips, and fingers following each "Localizer" paradigm. Multiple
      somatotopic representations of the face, lips, and fingers were localized and
      mapped in primary motor cortex (MI), ventral premotor cortex (PMv), polysensory
      zone (PZ), primary (SI) and secondary (SII) somatosensory cortex, parietal
      ventral area (PV) and 7b, as well as anterior and ventral intraparietal areas
      (AIP and VIP). The Dodecapus system is portable, easy to setup, generates no
      radio frequency interference, and can also be used for EEG and MEG experiments.
      This system could be useful for non-invasive somatotopic mapping in both basic
      and clinical studies.

PMID- 17182261
TI  - Bilateral temporal lobe epilepsy in a patient with Turner syndrome mosaicism.
AB  - Turner's syndrome (TS), resulting from deletion of one X chromosome in women, is
      associated with cerebral development abnormalities, particularly in the temporal
      lobes. Symptomatic epilepsy is described only in cases with extensive
      malformations. Here, we report the first case of bilateral temporal epilepsy
      without macroscopic cerebral malformation in a woman with TS mosaicism.
      Bitemporal dysfunction was confirmed by the ictal and interictal EEG, PET, MR
      spectroscopy and the neuropsychological examination, other causes than TS
      mosaicism were excluded. In rare cases, TS mosaicism may underlie non-lesional
      temporal lobe epilepsy, probably in relation to microanatomic structural and
      functional cerebral abnormalities. Further studies are needed to determine the
      frequency of this association.

PMID- 17182263
TI  - Thalidomide for treatment of PFAPA syndrome.

PMID- 17182262
TI  - Antigen-loading compartments for major histocompatibility complex class II
      molecules continuously receive input from autophagosomes.
AB  - Major histocompatibility complex (MHC) class II molecules present products of
      lysosomal proteolysis to CD4(+) T cells. Although extracellular antigen uptake is
      considered to be the main source of MHC class II ligands, a few intracellular
      antigens have been described to gain access to MHC class II loading after
      macroautophagy. However, the general relevance and efficacy of this pathway is
      unknown. Here we demonstrated constitutive autophagosome formation in MHC class
      II-positive cells, including dendritic, B, and epithelial cells. The
      autophagosomes continuously fuse with multivesicular MHC class II-loading
      compartments. This pathway was of functional relevance, because targeting of the
      influenza matrix protein 1 to autophagosomes via fusion to the autophagosome
      associated protein Atg8/LC3 led to strongly enhanced MHC class II presentation to
      CD4(+) T cell clones. We suggest that macroautophagy constitutively and
      efficiently delivers cytosolic proteins for MHC class II presentation and can be
      harnessed for improved helper T cell stimulation.

PMID- 17182264
TI  - Measuring the height of ponies at the withers: influence of time of day, water
      and feed withdrawal, weight-carrying, exercise and sedation.
AB  - Measuring the height at the withers of a pony is one of the requirements of the
      Federation Equestre Internationale (FEI), before competitors can participate in
      an official pony event. A pony has to be measured each year until it is eight
      years old. With and without shoes the height at the withers must be below 149.0cm
      and 148.0cm, respectively. When a pony exceeds the regulated height, it is
      excluded from participating in FEI pony competitions. Besides being excluded from
      competing, the selling price of the pony decreases dramatically, because the
      animal is then classified as a horse. For these reasons some owners may be
      tempted to try to influence wither height. The aim of the study was to determine
      whether the height of a pony at the withers can be influenced by variables such
      as time of day, water and feed withdrawal, weight carrying, exercise or sedation.
      To see if there was any influence of these variables on the measured height, the
      animals were measured at the beginning of the experiment and after completion,
      according to a standardized protocol. Fifteen healthy horses aged 7-17 years old
      and 16 healthy ponies aged 5-18 years were used for the study. A statistical
      evaluation determined whether there was a significant difference between the
      height at the withers before and after the experiment (P<0.05). Time of day,
      water and feed withdrawal, carrying weight, exercise and sedation all tended to
      decrease the height at the withers, but, with the exception of the data collected
      from the sedation-trial, the results were not significant. At the beginning of
      the experiment, the mean height at the withers of all eight animals was 165.0+/
      4.6cm; 15min after giving a standard dose of 5microg/kg detomidine-HCl per horse
      IV, the mean height had decreased to 163.7+/-4.5cm. Even 2h after administration
      of the sedative, the mean height at the withers was still 163.7+/-4.6cm. However,
      at both measuring points, it was still clinically apparent that the animals were
      sedated. The results demonstrate that it is not possible for owners to
      significantly influence the height at the withers except by administrating a
      sedative.

PMID- 17182265
TI  - A quantum chemical study of the mechanism of action of Vitamin K carboxylase
      (VKC) III. Intermediates and transition states.
AB  - A reaction path including transition states is generated for the Dowd mechanism
      [P. Dowd, R. Hershlne, S.W. Ham, S. Naganathan. Vitamin K and energy
      transduction: a base strength amplification mechanism. Science 269 (2005) 1684
      1691] of action for Vitamin K carboxylase (VKC) using quantum chemical methods
      (B3LYP/6-311G**). VKC, an essential enzyme in mammalian systems, catalyzes the
      conversion of hydroquinone form of Vitamin K to the epoxide form in the presence
      of oxygen. An intermediate species of the oxidation of Vitamin K, an alkoxide,
      acts apparently to abstract the gamma hydrogen from specifically located
      glutamate residues. We are able to follow the Dowd proposed path to generate this
      alkoxide species. The geometries of the proposed model intermediates and
      transition states in the mechanism are energy optimized. We find that the most
      energetic step in the mechanism is the uni-deprotonation of the hydroquinone -
      once this occurs, there is only a small barrier of 3.5kcal/mol for the
      interaction of oxygen with the carbon to be attacked - and then the reaction
      proceeds downhill in free energy to form the critical alkoxide species. The
      results are consistent with the idea that the enzyme probably acts to facilitate
      the formation of the epoxide by reducing the energy required to deprotonate the
      hydroquinone form.

PMID- 17182266
TI  - A quantum chemical study of the mechanism of action of Vitamin K epoxide
      reductase (VKOR) II. Transition states.
AB  - A reaction path including transition states is generated for the Silverman
      mechanism [R.B. Silverman, Chemical model studies for the mechanism of Vitamin K
      epoxide reductase, J. Am. Chem. Soc. 103 (1981) 5939-5941] of action for Vitamin
      K epoxide reductase (VKOR) using quantum mechanical methods (B3LYP/6-311G**).
      VKOR, an essential enzyme in mammalian systems, acts to convert Vitamin K
      epoxide, formed by Vitamin K carboxylase, to its (initial) quinone form for
      cellular reuse. This study elaborates on a prior work that focused on the
      thermodynamics of VKOR [D.W. Deerfield II, C.H. Davis, T. Wymore, D.W. Stafford,
      L.G. Pedersen, Int. J. Quant. Chem. 106 (2006) 2944-2952]. The geometries of
      proposed model intermediates and transition states in the mechanism are energy
      optimized. We find that once a key disulfide bond is broken, the reaction
      proceeds largely downhill. An important step in the conversion of the epoxide
      back to the quinone form involves initial protonation of the epoxide oxygen. We
      find that the source of this proton is likely a free mercapto group rather than a
      water molecule. The results are consistent with the current view that the widely
      used drug Warfarin likely acts by blocking binding of Vitamin K at the VKOR
      active site and thereby effectively blocking the initiating step. These results
      will be useful for designing more complete QM/MM studies of the enzymatic pathway
      once three-dimensional structural data is determined and available for VKOR.

PMID- 17182268
TI  - [Ovarian stimulation and cancers. Zero risk is but a myth... yet, should we
      terrorize our patients in the name of the precaution principle?].

PMID- 17182267
TI  - Long-term results of infliximab therapy in rheumatoid arthritis: experience
      acquired by the North-Pas-de-Calais hospital network.
AB  - OBJECTIVE: Infliximab is effective in patients with rheumatoid arthritis (RA).
      Add-on infliximab therapy in patients on methotrexate results in a rapid gain in
      effectiveness, which lasts at least 1 year. The objective of this study was to
      evaluate the effectiveness and continuation rate of infliximab in patients with
      RA after the first year of treatment. METHODS: The first 50 patients with RA who
      were given infliximab in the North-Pas-de-Calais region of France were included
      in a multicenter open-label study. The patients had severe RA or failed to
      respond to conventional medications. Infliximab was given in a dosage of 3 mg/kg
      every 8 weeks in combination with methotrexate. Effectiveness was evaluated using
      the DAS28-3 score and EULAR response criteria. The dates and reasons of
      infliximab discontinuations were recorded. RESULTS: The 2-year infliximab
      continuation rate was 70%. Serious adverse events requiring infliximab
      discontinuation occurred in 7 patients. Mean DAS28-3 scores in the 35 patients
      who took infliximab for at least 2 years were 6.42 at baseline, 4.33 after 30
      weeks, 4.31 after 54 weeks, and 3.86 after 102 weeks. According to EULAR criteria
      after 102 weeks, there were 12 good responders, 18 moderate responders, and 5
      nonresponders. CONCLUSION: Experience acquired in the North-Pas-de-Calais
      district of France suggests that infliximab is continued for more than 2 years in
      more than two-thirds of patients and remains effective over this period.

PMID- 17182269
TI  - Higher smoking prevalence in urban compared to non-urban areas: time trends in
      six European countries.
AB  - We investigated differences in smoking prevalence between urban and non-urban
      area of residence in six Western European countries (Sweden, Finland, Denmark,
      Germany, Italy and Spain), and smoking prevalence trends over the period 1985
      2000. In most countries, smoking prevalence was highest in urban areas, and
      increased with urbanization. Urban/non-urban inequalities were most pronounced
      among individuals with low education levels, and also among females. There were
      no significant differences in annual rate of change in smoking prevalence between
      non-urban and urban areas.

PMID- 17182270
TI  - Judd-Ofelt analysis of Tm and energy transfer studies between Tm and Er codoped
      in lithium tellurite network.
AB  - Optical properties of Tm(3+) and Er(3+) and Tm(3+)+Er(3+) codoped tellurite glass
      have been studied using different wavelengths from a Ti-Sapphire laser as
      excitation source. The energy transfer from one rare earth to other on excitation
      with different wavelengths has been studied. The Judd-Ofelt theory has been used
      to calculate various optical parameters suitable for laser oscillation.

PMID- 17182271
TI  - Synthesis, spectral, catalytic and antimicrobial studies of PPh3/AsPh3 complexes
      of Ru(II) with dibasic tridentate O, N, S donor ligands.
AB  - Complexes of the type [Ru(CO)(EPh(3))(B)(L)] (E = P or As; B = PPh(3), AsPh(3),
      py or pip; L=dianion of the Schiff bases derived from thiosemicarbazone with
      acetoacetanilide, acetoacet-o-toluidide and o-chloro acetoacetanilide) have been
      synthesized from the reactions of equimolar amounts of [RuHCl(CO)(EPh(3))(2)(B)]
      and Schiff bases in benzene. The new complexes have been characterized by
      analytical and spectral (IR, electronic, NMR) data. The arrangement of PPh(3)
      groups around ruthenium metal was determined from (31)P NMR spectra. An
      octahedral structure has been assigned for all the new complexes. All the
      complexes exhibited catalytic activity for the oxidation of benzyl alcohol and
      cyclohexanol in presence of N-methylmorpholine-N-oxide as co-oxidant. The
      complexes also exhibited antibacterial activity against E. coli, Aeromonas
      hydrophilla and Salmonella typhi. The activity was compared with standard
      streptomycin.

PMID- 17182272
TI  - Identification of polycyclic aromatic hydrocarbons (PAHs) in suspended
      particulate matter by synchronous fluorescence spectroscopic technique.
AB  - The synchronous fluorescence (SF) technique has been used in the identification
      of polycyclic aromatic hydrocarbons (PAHs) from air particulate sample in an
      urban environment of Delhi, Jawaharlal Nehru University. Suspended particulate
      matter samples of 24h duration were collected on glass fiber filter papers. PAHs
      were extracted from the filter papers using dichloromethane (DCM)+hexane with
      ultrasonication method. Qualitative measurements of the polycyclic aromatic
      hydrocarbons (PAHs) were carried out using the SF technique at various wavelength
      intervals (Deltalambda). Due to the difference in chemical structure, each PAH
      gives specific characteristic spectrum for each Deltalambda. Following PAHs were
      detected in our measurement: benz(a)anthracene (BaA), pyrene (Pyr), chrysene
      (Chry), fluoranthene (Flan), phenanthrene (Phen), and benz(ghi)perylene (BghiP).
      This is in agreement with our earlier work for determination of these PAHs using
      gas chromatography (GC). The seasonal variation of the PAHs was found to be
      maximum in winter and minimum during the monsoon.

PMID- 17182273
TI  - Review editorial comments.

PMID- 17182274
TI  - Study on the inclusion interaction of p-sulfonated calix[n]arenes with Vitamin K3
      using methylene blue as a spectral probe.
AB  - The characteristics of host-guest complexation between p-sulfonated calix[n]arene
      (SCnA, n = 4, 6) and Vitamin K(3) (VK(3)) were investigated by fluorescence
      spectrometry and absorption spectrometry using methylene blue (MB) as a probe.
      Interaction with MB and SCnA led to an obvious decrease in fluorescence intensity
      of MB, accompanying with shifts of emission peaks. Absorption peaks also showed
      interesting changes; however, when VK(3) was added, fluorescence intensity and
      absorbance recovered and a slight and slow red shift was observed. The obtained
      results showed that the inclusion ability of p-sulphonated calix[n]arenes towards
      VK(3) was the order: p-sulphonated calix[6]arene (SC6A) >p-sulphonated
      calix[4]arene (SC4A). Relative mechanism was proposed to explain the inclusion
      process.

PMID- 17182275
TI  - Highly sensitive detection of benzyl free radical in the vapor phase.
AB  - The 1(2)B(2)-->3(2)B(2) transition in the absorption spectrum of the benzyl free
      radical has been recorded in the vapor phase together with a new band at shorter
      wavelengths, probably the first Rydberg band of the radical in the vapor phase.
      The photolysis flash was of short duration and it was possible to follow the
      kinetics of the radicals' decay, which occurred predominantly by bimolecular
      recombination.

PMID- 17182276
TI  - EPR of VO2+ in double format, Ba2Zn(HCOO)6(H2O)4 single crystals.
AB  - VO(2+) doped single crystal of Ba(2)Zn(HCOO)(6)(H2O)(4) (BZFA) were investigated
      using electron paramagnetic resonance (EPR) technique at ambient temperature.
      Detailed investigation of EPR spectra indicated that the VO(2+) substitutes the
      Zn(2+) in the structure. The sites with different orientations were observed for
      VO(2+) in Ba(2)Zn(HCOO)(6)(H2O)(4).single crystal, but the only intense site
      among these sites was evaluated to obtain spin-Hamiltonian parameters, which are
      the principal axis values of the g and the hyperfine tensors. The covalent
      bonding parameter for VO(2+) and Fermi contact term were calculated using the
      spin-Hamiltonian parameters.

PMID- 17182277
TI  - Permanent loss of anti-HBc after reactivation of hepatitis B virus infection in
      an anti-HBs and anti-HBc-positive patient after allogeneic stem cell
      transplantation.
AB  - BACKGROUND: Reactivation of a hepatitis B virus (HBV) infection after
      transplantation is associated with a high morbidity and mortality. HBV infections
      generally result in anti-HBc persisting lifelong. CASE REPORT: A 44-year-old
      female presented 10 years after allogeneic stem cell transplantation with a
      chronic hepatitis B. The infection was reactivated from a resolved (anti-HBs and
      anti-HBc positive) HBV infection acquired some years prior to transplantation.
      Interestingly, she lost all antibodies to HBV including anti-HBc and is upto now
      anti-HBc negative. The sequence of the surface and the core gene did not reveal
      any escape mutations. Thus, the loss of anti-HBc might suggest an immunotolerance
      of the donor's immune system against HBcAg. CONCLUSION: This data illustrate that
      an HBV infection might be reactivated despite high anti-HBs levels prior to
      transplantation. Furthermore, this is the first patient in which a complete loss
      of anti-HBc could be documented. Moreover, since anti-HBc is often used as a
      screening marker for HBV it should be kept in mind that anti-HBc negative
      patients with high viremic HBV infection may occur.

PMID- 17182278
TI  - Occurrence and daily variation of phthalate metabolites in the urine of an adult
      population.
AB  - Phthalates like di-(2-ethylhexyl) phthalate (DEHP) are commonly used as
      plasticizers and their metabolites are suspect of especially reproductive
      toxicity. The aim of our study was to assess phthalate exposure in adults by
      measuring urinary phthalate metabolite levels and to explore individual temporal
      variability. Urine samples were collected by 27 women and 23 men aged 14-60 years
      during 8 consecutive days. We quantified four monoesters, four oxidative DEHP
      metabolites, and two secondary metabolites of di-isononyl phthalate (DiNP) by a
      LC/LC-MS/MS method. If we analyzed all 399 available samples independent of
      classification, the highest median values of primary metabolites in this study
      were found for mono-n-butyl phthalate (MnBP: 49.6 microg/l), followed by mono
      isobutyl phthalate (MiBP: 44.9 microg/l), mono-benzyl phthalate (MBzP: 7.2
      microg/l), and mono-2-ethylhexyl phthalate (MEHP: 4.9 microg/l). The median
      concentrations of the oxidized metabolites of DEHP were 8.3 microg/l for mono-(2
      carboxymethylhexyl) phthalate (2cx-MMHP), 19.2 microg/l for mono-(2-ethyl-5
      hydroxyhexyl) phthalate (5OH-MEHP), 14.7 microg/l for mono-(2-ethyl-5-oxohexyl)
      phthalate (5oxo-MEHP), and 26.2 microg/l for mono-(2-ethyl-5-carboxypentyl)
      phthalate (5cx-MEPP). The concentrations of the two DiNP secondary metabolites
      mono (oxoisononyl) phthalate (oxo-MiNP) and mono(hydroxyisononyl) phthalate (OH
      MiNP) ranged from <LOD to 304 microg/l (median: 3.0 microg/l, 2.9 microg/g
      creatinine) and <LOD to 698 microg/l (median: 5.5 microg/l, 5.2 microg/g
      creatinine), respectively. Phthalate metabolite levels did not consistently
      differ by sex or age. There was substantial day-to-day variation of urinary
      levels with considerable within-subject variability. Intraclass correlation
      coefficients adjusted for sex and age ranged between 0.21 and 0.48 for unadjusted
      metabolite levels and between 0.20 and 0.57 for creatinine-adjusted levels. The
      secondary metabolites of DiNP were detectable in nearly all samples and were
      therefore sensitive biomarkers of DiNP exposure. Our results of within-subject
      variability suggest that exposure assessment should not be based on a single
      urine measurement.

PMID- 17182279
TI  - Di-iso-nonylphthalate (DINP) metabolites in human urine after a single oral dose
      of deuterium-labelled DINP.
AB  - Di-iso-nonylphthalate (DINP), a complex mixture of predominantly nine-carbon
      branched chain dialkyl phthalate isomers, has replaced di-(2-ethylhexyl)phthalate
      (DEHP) as the major plasticiser for polyvinylchloride (PVC) polymers. Similar to
      DEHP, DINP is a developmental and reproductive toxicant in rodents. This study
      for the first time describes human metabolism and elimination of DINP in a male
      volunteer after we applied a single oral DINP dose of 1.27 mg/kg body-weight. To
      avoid interference by omnipresent background exposure we used deuterium-labelled
      DINP. We investigated the urinary excretion of the simple monoester mono-iso
      nonylphthalate (MINP) and oxidised isomers with hydroxy (OH-MINP), oxo (oxo-MINP)
      and carboxy (carboxy-MINP) functional groups. We used isomeric MINP and three
      specific oxidised isomer standards for quantification: mono-(4-methyl-7-hydroxy
      octyl)phthalate (7OH-MMeOP), mono-(4-methyl-7-oxo-octyl)phthalate (7oxo-MMeOP)
      and mono-(4-methyl-7-carboxyheptyl)phthalate (7carboxy-MMeHP). These specific
      DINP metabolites are currently the only synthetic DINP metabolite standards
      available. Within 48 h we recovered 43.6% of the applied dose in urine as the
      above DINP metabolites, 20.2% as OH-MINP, 10.7% as carboxy-MINP, 10.6% as oxo
      MINP and only 2.2% as MINP. Other oxidised DINP metabolites not determined in
      this study probably increase the share of the DINP dose excreted via urine.
      Elimination followed a multi-phase pattern, elimination half-lives in the second
      phase (beginning 24h post-dose) can only roughly be estimated to be 12h for the
      OH- and oxo-MINP-metabolites and 18 h for carboxy-MINP metabolites. After 24h,
      the carboxy-MINP metabolites replaced the OH-MINP metabolites as the major
      urinary metabolites. All oxidised DINP metabolites are suitable parameters for
      biomonitoring human DINP exposure.

PMID- 17182280
TI  - Is part of the mystery surrounding fatigue complicated by context?
AB  - Historically, research into possible causes of exercise-induced fatigue has been
      found to span numerous scientific disciplines, including medicine, psychology,
      physiology, neurophysiology, biochemistry, biomechanics, and physics. In order to
      better understand the mechanisms responsible for fatigue, these disciplines have
      viewed various aspects of fatigue, including the involvement of physiological,
      physical, biomechanical, and/or psychological factors. This has resulted in a
      diverse array of interpretations of the term 'fatigue' among the scientific
      disciplines. For instance, the word 'fatigue' has been used to define a sensation
      of tiredness, a physical reduction in force, or the failure of a specific
      physiological system to maintain homeostatic integrity. As sports scientists
      begin to take on a holistic approach to understanding fatigue, it seems necessary
      that the 'context' should be highlighted when using the term and questioning the
      mystery behind it.

PMID- 17182281
TI  - Abstracts of the ASICS Conference of Science and Medicine in Sport. Fiji. 19-21
      October 19-21, 2006.

PMID- 17182282
TI  - Altered chloride homeostasis in neurological disorders: a new target.
AB  - Other than modifying either neurotransmitter release or receptor expression
      and/or properties, one way to modulate gamma-aminobutyric acid (GABA)A and
      glycine receptor-mediated signalling is to alter the transmembrane gradient for
      chloride ions. Because intracellular chloride concentration is low in neurons,
      and the reversal potential for chloride currents is close to the resting membrane
      potential, small changes in intracellular chloride concentration can dramatically
      affect the strength and even polarity of GABA/glycine-mediated transmission. It
      now appears that chloride homeostasis is actively regulated in the adult brain
      and affected by endogenous neuromodulators such as brain-derived neurotrophic
      factor. Modulating chloride gradients even emerges as a mechanism by which
      microglia can control neuronal excitability. These findings, together with the
      observation of altered chloride homeostasis in several neurological disorders,
      point to new targets for therapeutic agents.

PMID- 17182283
TI  - Superexpression of tuberculosis antigens in plant leaves.
AB  - Recent developments in genetic engineering allow the employment of plants as
      factories for 1/foreign protein production. Thus, tuberculosis (TB) ESAT6 antigen
      was expressed in different plant systems, but the level of vaccine protein
      accumulation was extremely low. We describe the technology for superexpression of
      TB vaccine proteins (Ag85B, ESAT6, and ESAT6:Ag85B fusion) in plant leaves which
      involves: (i) construction of tobacco mosaic virus-based vectors with the coat
      protein genes substituted by those for TB antigens; (ii) Agrobacterium-mediated
      delivery to plant leaf tissues of binary vectors containing the cDNA copy of the
      vector virus genome; and (iii) replication of virus vectors in plant cells under
      conditions suppressing the virus-induced gene silencing. This technology enables
      efficient production of the TB vaccine proteins in plants; in particular, the
      level of Ag85B antigen accumulation was not less than 800 mg/kg of fresh leaves.
      Expression of TB antigens in plant cells as His(6)-tagged proteins promoted their
      isolation and purification by Ni-NTA affinity chromatography. Deletion of
      transmembrane domains from Ag85B caused a dramatic increase in its intracellular
      stability. We propose that the strategy of TB antigens superproduction in a plant
      might be used as a basis for the creation of prophylactic and therapeutic vaccine
      against TB.

PMID- 17182284
TI  - Immune suppression via IL-4/IL-10-secreting T cells: a nontoxic property of anti
      HIV agent trichosanthin.
AB  - The activity of Trichosanthin (Tk) has been attributed to its toxicity since this
      plant protein was used as an anti-HIV agent. However, in this study strong
      inhibition of human lymphoproliferation to soluble and allogeneic antigens was
      induced by Tk at 0.005-0.5 microg/ml without causing cell damages including
      apoptosis. The suppression was dependent on the presence of monocytes that are
      able to internalize and process Tk molecules as exogenous antigens. Among 39 Tk
      primed T cell lines established, those with strong suppressive activity were
      CD8(+) TCRalphabeta(+) with type 2 cytokine secretion profile. Depletion of CD8
      cells from total T cells or blocking expression of HLA-DQ molecules diminished
      Tk's inhibitory activity. In addition, healthy subjects with HLA haplotype
      DRB1*0301-DQA1*0501-DQB1*0201 were susceptible to the hyporeaction induced by Tk
      or a Tk-derived peptide. This indicates that Tk could induce an HLA-associated
      immune suppression via activating IL-4/IL-10-secreting T cells, which might
      belong to CD8 Tc2 subset.

PMID- 17182285
TI  - Information infrastructure for inter-organizational mental health services: an
      actor network theory analysis of psychiatric rehabilitation.
AB  - In the supply of mental health services to communities, data and information are
      managed not only by clinical organizations, but also by welfare state agencies
      and charities. The aim of this study is to use methods of analysis from actor
      network theory to identify organizational interventions necessary for the
      development of an information infrastructure for inter-organizational mental
      health services. Data was collected in a project aimed at developing an
      information system that supports inter-organizational psychiatric rehabilitation
      in a Swedish municipality. Three organizational interventions were identified: an
      integrated service policy defined by the national government, a common legal
      framework allowing sharing of high-level client data, and commissioned support
      for local inter-agency workspaces. It is concluded that organizational
      interventions must be regarded when configuring an information infrastructure for
      mental health services. Organizational interventions should also routinely be
      addressed in systems design methods to be used in inter-organizational settings.

PMID- 17182286
TI  - Clinical trials and the response rate illusion.
AB  - Clinical trial outcome data can be presented and analyzed as mean change scores
      or as response rates. These two methods of presenting the data can lead to
      divergent conclusions. This article explores the reasons for the apparently
      divergent outcomes produced by these methods and considers their implications for
      the analysis and reportage of clinical trial data. It is shown that relatively
      small differences in improvement scores can produce relatively large differences
      in expected response rates. This is because differences in response rates do not
      indicate differences in the number of people who have improved; they indicate
      differences in the number of people whose degree of improvement has pushed them
      over a specified criterion. Therefore, patients classified as non-responders may
      have shown substantial and clinically significant improvement, and these are the
      patients who are most likely to become responders when given medication. Response
      rates based on continuous data do not add information, and they can create an
      illusion of clinical effectiveness.

PMID- 17182287
TI  - Wood creosote prevents CRF-induced motility via 5-HT3 receptors in proximal and 5
      HT4 receptors in distal colon in rats.
AB  - Wood creosote has been used as an herbal medicine against acute diarrhea caused
      by food poisoning and has an inhibitory effect on colonic motility and
      enterotoxin-induced ion secretion. Since no previous studies have examined the
      effects of wood creosote on stress-induced alteration of colonic motility, we
      examined the effects on the colonic motility altered by intracerebroventricular
      (i.c.v.) injection of corticotropin-releasing factor (CRF), which is a key
      mediator in responses to stress. We recorded motor activity in proximal and
      distal colon of unrestrained conscious rats via two manometory catheters. The
      frequencies of phase III-like contraction and the % motor indices in both
      proximal and distal colon were measured. At the same time the number of fecal
      pellets excreted was counted. I.c.v. injection of CRF increased the motor
      activity in both proximal and distal colon, and these effects were completely
      antagonized by i.c.v. injection of a selective CRF type 1 antagonist but not by a
      CRF type 2 antagonist. Changes in colonic motility induced by CRF were reversed
      by intravenously administered wood creosote. Intraluminal administration of the 5
      HT(3) receptor antagonist granisetron, or the 5-HT(4) receptor antagonist SB
      204070 blocked the increase in colonic motility induced by i.c.v. injection of
      CRF. Wood creosote prevented the increase in colonic motility induced by the 5
      HT(3) receptor agonist SR57227A in the proximal colon, while it prevented the
      increase in colonic motility induced by the 5-HT(4) receptor agonist RS67506 in
      the distal colon. These results indicate that wood creosote prevents the increase
      in colonic motility induced by CRF via 5-HT(3) receptors in the proximal colon,
      and via 5-HT(4) receptors in the distal colon, suggesting that wood creosote
      might be useful to treat stress-induced diarrhea.

PMID- 17182288
TI  - The temporal and spatial expression of Claudins in epidermal development and the
      accelerated program of epidermal differentiation in K14-CaSR transgenic mice.
AB  - The importance of the epidermal permeability barrier (EPB) in protecting the
      mammalian species against harmful UV irradiation, microorganism invasion and
      water loss is well recognized, as is the role of calcium (Ca(2+)) in keratinocyte
      differentiation, cell-cell contact and the EPB. In a previous study, we reported
      that the overexpression of the Ca(2+)-sensing receptor (CaSR) in the
      undifferentiated basal cells of the epidermis induced a modified epidermal
      differentiation program including an accelerated EPB formation in transgenic
      mice, suggesting a role for CaSR signaling in the differentiation of embryonic
      epidermal cells during development. We now describe the expression profile of
      claudins (Cldns) and keratin markers in the accelerated EPB formation of K14-CaSR
      transgenic mice during development as compared to the wild type from E12.5 to
      newborn stages. Our data show that the transgenic epidermis undergoes an advanced
      epidermal differentiation program as compared to the wild type as evidenced
      morphologically as well as by the expression of K14, K1, loricrin, Cldn6, Cldn18
      and Cldn11. In addition, we report for the first time the sequential expression
      of Cldns in epidermal development and describe that the localization of some
      Cldns change within the epidermis as it matures. Furthermore, we demonstrate that
      Cldn6 is expressed very early in epidermal morphogenesis, followed by Cldn18,
      Cldn11 and Cldn1.

PMID- 17182289
TI  - Beta-lactam allergy in adults with cystic fibrosis.
AB  - BACKGROUND: Allergic reactions to one or more beta-lactam antibiotic can pose a
      management problem in patients with cystic fibrosis (CF), and may limit
      antibiotic choice. METHOD: The aim of this study was to assess the prevalence of
      allergy to anti-pseudomonal beta-lactam antibiotics in an adult CF centre and to
      assess variables, which may contribute to the development of allergic reactions.
      A questionnaire-based interview and a review of medical records were performed.
      RESULTS: Of the 150 patients, 54 (36%) had allergic reactions to one or more beta
      lactam antibiotics and 20 (19%) had allergic reactions to multiple beta-lactam
      antibiotics. The proportion of patients allergic to specific beta-lactam
      antibiotics varied from 10% to 26%. Rates of reactions were highest for
      penicillins and cephalosporins, intermediate for carbepenems and lowest for
      aztreonam. Of all reactions, 40% occurred within 24 h of the commencement of an
      individual antibiotic course. Patients with one or more beta-lactam allergic
      reactions had received greater cumulative exposure (p<0.0001), were older
      (p=0.016) and had lower lung function (p=0.037) than patients without a history
      of beta-lactam allergy. Cystic Fibrosis transmembrane regulator (CFTR) status,
      gender, peripheral blood eosinophil count and total IgE concentrations were not
      different in patients with allergic reactions. CONCLUSIONS: This study
      demonstrates that the prevalence of allergic reactions to beta-lactam antibiotics
      is high in adults with CF. Increasing age; cumulative exposure and decreasing
      FEV(1) were associated with the development of allergy.

PMID- 17182290
TI  - Airway nociceptors activated by pro-inflammatory cytokines.
AB  - The present studies evaluate whether the vagus nerves link the lungs' immune and
      neural systems by transmitting information through pulmonary nociceptors. Single
      unit activities from pulmonary nociceptors [C fiber receptors (CFRs) and high
      threshold Adelta fiber receptors (HTARs)] were recorded from the cervical vagus
      nerve in anesthetized, open-chest, and mechanically ventilated rabbits.
      Interleukin1beta was then injected into the nociceptor field (IL-1beta, 10
      microg/ml, 20 microl). Both CFRs and HTARs were stimulated by the local
      injection; their activities increased from 0.2+/-0.1 to 1.8+/-0.5 imp/s (n=10;
      p<0.01), and from 0.2+/-0.1 to 1.1+/-0.1 imp/s, respectively (n=6; p<0.01). These
      increases were greatly attenuated by simultaneous administration of IL-1beta with
      IL-1 ra, a natural IL-1 receptor antagonist. The nociceptors were not stimulated
      by local injection of normal saline. Our data demonstrate that nociceptors can be
      activated by pro-inflammatory cytokines and support the hypothesis that airway
      nociceptors transmit immune signals from the lung to the brain.

PMID- 17182291
TI  - Comparison of methionine oxidation in thermal stability and chemically stressed
      samples of a fully human monoclonal antibody.
AB  - Methionine (Met) oxidation is a major degradation pathway of protein
      therapeutics. Met oxidation of a fully human recombinant monoclonal antibody was
      investigated under both chemically stressed conditions using tert
      butylhydroperoxide (tBHP) and thermal stability conditions where the sample was
      incubated in formulation buffer at 25 degrees C for 12 months. This antibody has
      one Met residue on each of the light chains and four Met residues on each of the
      heavy chains. In the thermal stability sample, only Met residues 256 and 432 in
      the Fc region were oxidized to form methionine sulfoxide, while Met residues in
      the Fab region were relatively stable. The susceptibility of Met residues 256 and
      432 was further confirmed by incubating samples with tBHP, which has been shown
      to induce Met oxidation. Further analysis revealed that the susceptible Met
      residues of each heavy chain were randomly oxidized in samples incubated with
      tBHP, while in the thermal stability sample, the susceptible Met residues of one
      heavy chain were preferentially oxidized.

PMID- 17182292
TI  - Proteomic analyses of amniotic fluid: potential applications in health and
      diseases.
AB  - Amniotic fluid (AF) is a potential source of biomarkers for many disorders which
      may occur during pregnancy. The purpose of this study was to evaluate the place
      of two-dimensional gel electrophoresis (2-DE) technologies to compare AF in both
      normal and pathological situations. Two-dimensional fluorescence difference gel
      electrophoresis (2D-DIGE; Ettan DIGE) as well as two-dimensional gel
      electrophoresis and silver staining followed by image analysis were used.
      Differentially expressed proteins were identified by mass spectrometry. This
      approach was used to study electrophoregrams of normal AF obtained at 17 weeks of
      gestation and at term, as well as AF from fetuses presenting with congenital
      diaphragmatic hernia. Finally, the potential of two-dimensional electrophoresis
      was assessed by studying the protein profile of plasma containing AF proteins in
      a model of premature rupture of the membranes (PROM). Our results clearly show
      that two-dimensional electrophoresis technologies still have place for analyzing
      biological fluids such as AF.

PMID- 17182293
TI  - Was there an urban height penalty in Spain, 1840-1913?
AB  - We explore whether there was an urban height penalty in Spain during the period
      of early industrialization from 1840 to 1913, using data from Spain's
      Southeastern coast and from Castile-Leon. Our results indicate that in the
      Mediterranean Coast of Southeastern Spain urban heights were well above rural
      ones for most of the period considered. In Castile-Leon, however, urban and rural
      heights were about the same until 1870 but urban heights were intermittently
      above rural ones thereafter. Hence, in Spain urban heights were not always below
      rural ones in stark contrast to the pattern obtained in other parts of Europe and
      North America.

PMID- 17182294
TI  - The pH dependence of the activity of dehaloperoxidase from Amphitrite ornata.
AB  - Dehaloperoxidase (DHP) from the terebellid polychaete, Amphitrite ornata, is the
      first hemoglobin that has peroxidase activity as part of its native function. The
      substrate 2,4,6-tribromophenol (TBP) is oxidatively debrominated by DHP to form
      2,6-dibromoquinone (DBQ) in a two-electron process. There is a well-defined
      internal binding site for TBP above the heme, a feature not observed in other
      hemoglobins or peroxidases. A study of the pH dependence of the activity of DHP
      reveals a substantial difference in mechanism. From direct observation of the
      Soret band of the heme it is shown that the pKa for heme activation in protein
      DHP is 6.5. Below this pH the heme absorbance decreases in the presence of H2O2
      with or without addition of substrate. The low pH data are consistent with
      significant heme degradation. Above pH 6.5 addition of H2O2 causes the heme to
      shift rapidly to a compound II spectrum and then slowly to an unidentified
      intermediate with an absorbance of 410 nm. However, the pKa of the substrate TBP
      is 6.8 and the greatest enzyme activity is observed above the pKa of TBP under
      conditions where the substrate is a phenolate anion (TPBO-). Although the
      mechanisms may differ, the data show that both neutral TBP and anionic TPBO- are
      converted to the quinone product. The mechanistic implications of the pH
      dependence are discussed by comparison other known peroxidases, which oxidize
      substrates at the heme edge.

PMID- 17182295
TI  - Hydrolysis of oxo- and thio-esters by human butyrylcholinesterase.
AB  - Catalytic parameters of human butyrylcholinesterase (BuChE) for hydrolysis of
      homologous pairs of oxo-esters and thio-esters were compared. Substrates were
      positively charged (benzoylcholine versus benzoylthiocholine) and neutral
      (phenylacetate versus phenylthioacetate). In addition to wild-type BuChE, enzymes
      containing mutations were used. Single mutants at positions: G117, a key residue
      in the oxyanion hole, and D70, the main component of the peripheral anionic site
      were tested. Double mutants containing G117H and mutations on residues of the
      oxyanion hole (G115, A199), or the pi-cation binding site (W82), or residue E197
      that is involved in stabilization of tetrahedral intermediates were also studied.
      A mathematical analysis was used to compare data for BuChE-catalyzed hydrolysis
      of various pairs of oxo-esters and thio-esters and to determine the rate-limiting
      step of catalysis for each substrate. The interest and limitation of this method
      is discussed. Molecular docking was used to analyze how the mutations could have
      altered the binding of the oxo-ester or the thio-ester. Results indicate that
      substitution of the ethereal oxygen for sulfur in substrates may alter the
      adjustment of substrate in the active site and stabilization of the transition
      state for acylation. This affects the k2/k3 ratio and, in turn, controls the rate
      limiting step of the hydrolytic reaction. Stabilization of the transition state
      is modulated both by the alcohol and acyl moieties of substrate. Interaction of
      these groups with the ethereal hetero-atom can have a neutral, an additive or an
      antagonistic effect on transition state stabilization, depending on their
      molecular structure, size and enantiomeric configuration.

PMID- 17182296
TI  - Clinical risk factors for fracture in postmenopausal Canadian women: a population
      based prevalence study.
AB  - Clinical risk factor assessment can be used to enhance fracture risk estimation
      based upon bone densitometry alone. Population- and age-specific risk factor
      prevalence data are required for the construction of these risk models. Our
      objective was to derive population-based prevalence estimates of specific
      clinical risk factors for postmenopausal women resident in the Province of
      Manitoba, Canada. A random sample of 40,300 women age 50 or older identified from
      the provincial health plan was mailed a validated self-report risk factor survey.
      The response rate was 8747 (21.7%) with a final study population of 8027 women
      after exclusions. The individual prevalence for each clinical risk factor ranged
      from 5.8% for hyperthyroidism to 33.0% for a fall in the preceding 12 months.
      Most point prevalence estimates were similar to other large cohort studies,
      though the prevalences of inactivity and poor mobility were higher than expected
      while height at age 25 and the prevalence of any fracture after age 50 were lower
      than expected. Most of the respondents (86.9%) had at least one non-age clinical
      risk factor, 60.6% had two or more, and 33.5% had three or more. Age affected
      risk factor prevalence, and older age was associated with a higher rate of
      multiple risk factors. The availability of age-specific risk factor prevalence
      rates in this population may allow for more accurate fracture risk modeling.

PMID- 17182297
TI  - Comparative effects of raloxifene and alendronate on fracture outcomes in
      postmenopausal women with low bone mass.
AB  - The double-blind, randomized raloxifene alendronate comparison trial was the
      first study designed to compare two osteoporosis therapies head-to-head for
      fracture risk reduction. The original protocol planned to treat 3000
      postmenopausal women with alendronate 10 mg/day (ALN) or raloxifene 60 mg/day
      (RLX) for 5 years, and to recruit women (50-80 years old) with a femoral neck
      bone mineral density (BMD) T-score between -2.5 and -4.0, inclusive, no prevalent
      vertebral fractures, and no prior bone-active agent use. The trial was stopped
      early, due to difficulty in finding treatment-naive women to meet enrollment
      goals within the planned timeline, resulting in insufficient power to show non
      inferiority between therapies in the primary endpoint (number of women with >or=1
      new osteoporotic vertebral or nonvertebral fracture). Except for vertebral
      fractures, fracture analyses were based upon 1412 of the 1423 women randomized
      (mean age of 66 years). After 312+/-254 days (mean+/-SD), 22 women in the ALN
      group and 20 in the RLX group had new vertebral or nonvertebral fractures. Four
      women in the ALN group and none in the RLX group had moderate/severe vertebral
      fractures, a pre-specified endpoint (P=0.04). Lumbar spine, femoral neck, and
      total hip BMD were increased from baseline at 2 years in each group (P<0.001),
      with greater increases in the ALN group (each P<0.05). Similar numbers of women
      in each group had >or=1 adverse event and discontinued due to an adverse event.
      The only adverse events with an incidence that differed between groups were
      colonoscopy, diarrhea, and nausea; each was more common with ALN treatment (each
      P<0.05). One woman in each group had a venous thromboembolic event. One case of
      breast cancer occurred in each group. In summary, as this trial was terminated
      early, there was insufficient power to compare the fracture risks between
      alendronate and raloxifene. Safety profiles were as expected from clinical trial
      and post-marketing reports. TRIAL REGISTRATION: ClinicalTrials.gov Identifier
      NCT00035971.

PMID- 17182318
TI  - Metabolic modelling and the closed-loop insulin delivery problem.
AB  - The approach used by Medtronic MiniMed to close the insulin delivery loop using
      the subcutaneous site for both glucose sensing and insulin delivery relies on
      modeling insulin action and beta-cell insulin secretion. This approach is
      contrasted with traditional control systems engineering.

PMID- 17182301
TI  - Continuous subcutaneous insulin infusion (CSII) in children with type 1 diabetes.
AB  - Recent studies have shown that continuous subcutaneous insulin infusion (CSII),
      or insulin pump therapy, provides a treatment option that can assist in the
      attainment of current goals of treatment in children and adolescents with type 1
      diabetes (T1DM). In pediatric patients, CSII has been demonstrated to reduce both
      glycosylated hemoglobin levels and frequency of severe hypoglycemia, without
      sacrifices in safety, quality of life, or excessive weight gain, particularly in
      conjunction with the use of new insulin analogs and improvements in pump
      technology. Clinical studies of safety and efficacy of CSII in children are
      reviewed.

PMID- 17182326
TI  - New models of population management for patients with diabetes--using informatics
      tools to support primary care.
AB  - Diabetes management continues to fall short of evidence-based goals of care.
      Population management represents a new approach to diabetes care for large
      numbers of patients with diabetes cared for within a single clinical system. This
      method is information intensive and generally requires an advanced informatics
      infrastructure. While Information Processing is a critical first step in
      population management, to have a significant impact on disease control population
      based intervention must also employ potent Clinical Action tools that lower
      barriers to effective care. In this review we present two recent population
      management interventions within our health system that illustrate the principles
      of Information Processing and Clinical Action in diabetes care.

PMID- 17182333
TI  - HIV in prisons.

PMID- 17182334
TI  - Evaluating the "A" component of the SAFE strategy.

PMID- 17182335
TI  - Responsibility in naming pathogens: the case of Pneumocystis jirovecii, the
      causal agent of pneumocystis pneumonia.

PMID- 17182338
TI  - Oral miltefosine to treat new world cutaneous leishmaniasis.

PMID- 17182336
TI  - When to start HAART for the treatment of HIV infection.

PMID- 17182339
TI  - Watch your bats.

PMID- 17182341
TI  - WHO Rapid Advice Guidelines for pharmacological management of sporadic human
      infection with avian influenza A (H5N1) virus.
AB  - Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has
      increased the threat of human infections with H5N1 virus worldwide. Despite
      international agreement to stockpile antivirals, evidence-based guidelines for
      their use do not exist. WHO assembled an international multidisciplinary panel to
      develop rapid advice for the pharmacological management of human H5N1 virus
      infection in the current pandemic alert period. A transparent methodological
      guideline process on the basis of the Grading Recommendations, Assessment,
      Development and Evaluation (GRADE) approach was used to develop evidence-based
      guidelines. Our development of specific recommendations for treatment and
      chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms,
      burden, and cost of interventions in several patient and exposure groups.
      Overall, the quality of the underlying evidence for all recommendations was rated
      as very low because it was based on small case series of H5N1 patients, on
      extrapolation from preclinical studies, and high quality studies of seasonal
      influenza. A strong recommendation to treat H5N1 patients with oseltamivir was
      made in part because of the severity of the disease. Similarly, strong
      recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in
      high-risk exposure populations. Emergence of other novel influenza A viral
      subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus
      strains, will require an update of these guidelines and WHO will be monitoring
      this closely.

PMID- 17182342
TI  - HIV in prison in low-income and middle-income countries.
AB  - High prevalence of HIV infection and the over-representation of injecting drug
      users (IDUs) in prisons combined with HIV risk behaviour create a crucial public
      health issue for correctional institutions and, at a broader level, the
      communities in which they are situated. However, data relevant to this problem
      are limited and difficult to access. We reviewed imprisonment, HIV prevalence,
      and the proportion of prisoners who are IDUs in 152 low-income and middle-income
      countries. Information on imprisonment was obtained for 142 countries.
      Imprisonment rates ranged from 23 per 100,000 population in Burkina Faso to 532
      per 100,000 in Belarus and Russia. Information on HIV prevalence in prisons was
      found for 75 countries. Prevalence was greater than 10% in prisons in 20
      countries. Eight countries reported prevalence of IDUs in prison of greater than
      10%. HIV prevalence among IDU prisoners was reported in eight countries and was
      greater than 10% in seven of those. Evidence of HIV transmission in prison was
      found for seven low-income and middle-income countries. HIV is a serious problem
      for many countries, especially where injection drug use occurs. Because of the
      paucity of data available, the contribution of HIV within prison settings is
      difficult to determine in many low-income and middle-income countries. Systematic
      collection of data to inform HIV prevention strategies in prison is urgently
      needed. The introduction and evaluation of HIV prevention strategies in prisons
      are warranted.

PMID- 17182343
TI  - Role of mini-host models in the study of medically important fungi.
AB  - Mini-host models have emerged as simple experimental systems to study the
      pathogenesis and host innate immune responses in fungal invaders and also to test
      drug efficacy against these organisms. A growing number of medically important
      fungi, including Aspergillus spp, Candida spp, Cryptococcus spp, and species in
      the class Zygomycetes, have been shown to infect and kill invertebrates such as
      roundworms, fruit flies, and wax moths. These studies have shown that several
      genes implicated in the virulence of fungi in mammalian models also have a
      similarly important pathogenic role in mini-host organisms. These mini-host
      models provide a unique opportunity of simultaneously exploring the molecular
      mechanisms of fungal pathogenicity and candidate agents with antifungal activity.
      Furthermore, the fact that some of these mini-hosts have well-defined genetics
      and conserved innate immunity offers the advantage of a comprehensive analysis of
      the molecular aspects of host immune response. We examine the relevance,
      advantages, and pitfalls of experimental systems of fungal infections in various
      mini-hosts and compare them with what is known in experimental systems in
      mammalian animal models.

PMID- 17182344
TI  - Childhood pneumonia and diarrhoea: setting our priorities right.
AB  - Childhood pneumonia and diarrhoeal disease cause almost half of all child deaths
      globally. Effective interventions against these conditions are available and
      could prevent about two-thirds of these deaths. We argue that part of the reason
      for the lack of success in delivering these interventions is the lack of
      attention to implementation challenges. We present a novel research priority
      setting model that shifts the emphasis from generation of new knowledge and
      publication to potential public-health outcomes, and propose a framework by which
      this new model can be put into operation. We believe that only in this way will
      proper attention be given to delivery of proven interventions to reduce the high
      childhood mortality caused by pneumonia and diarrhoea.

PMID- 17182345
TI  - Subdural empyema and other suppurative complications of paranasal sinusitis.
AB  - Suppurative intracranial infection, including meningitis, intracranial abscess,
      subdural empyema, epidural abscess, cavernous sinus thrombosis, and thrombosis of
      other dural sinuses, are uncommon sequelae of paranasal sinusitis. A high index
      of suspicion is necessary to identify these serious complications. We present a
      patient with subdural empyema in whom the diagnosis was delayed, followed by a
      discussion of suppurative complications of sinusitis. The case shows the rapid
      progression of subdural empyema, which represents a true neurosurgical emergency
      requiring prompt diagnosis and management.

PMID- 17182346
TI  - Anti-infective research and development--problems, challenges, and solutions.

PMID- 17182347
TI  - Prevention of esophageal variceal rebleeding.
AB  - The rate of rebleeding of esophageal varices remains high after cessation of
      acute esophageal variceal hemorrhage. Many measures have been developed to
      prevent the occurrence of rebleeding. When considering their effectiveness in
      reduction of rebleeding, the associated complications cannot be neglected. Due to
      unavoidable high incidence of complications, shunt surgery and endoscopic
      injection sclerotherapy are now rarely used. Transjugular intrahepatic
      portosystemic stent shunt was developed to replace shunt operation but is now
      reserved for rescue therapy. Nonselective beta-blockers alone or in combination
      with isosorbide mononitrate and endoscopic variceal ligation are currently the
      first choices in the prevention of variceal rebleeding. The combination of
      nonselective beta-blockers and endoscopic variceal ligation appear to enhance the
      efficacy. With the advent of newly developed measures, esophageal variceal
      rebleeding could be greatly reduced and the survival of cirrhotics with bleeding
      esophageal varices could thereby be prolonged.

PMID- 17182348
TI  - Is hypothyroidism a treatment option in conditions of liver injury and hepatic
      encephalopathy?

PMID- 17182349
TI  - Methimazole alleviates hepatic encephalopathy in bile-duct ligated cirrhotic
      rats.
AB  - BACKGROUND: Acute or chronic liver damage may lead to hepatic encephalopathy.
      Previous studies have indicated the hemodynamic and hormonal mimicry between
      portal hypertension and hyperthyroidism. Furthermore, medically or surgically
      induced hypothyroidism has been found to be beneficial in ameliorating
      hyperdynamic circulation in the portal hypertensive state and in alleviating
      acute or chronic liver injury in rats. However, the effect of chronic thyroid
      hormone inhibition on chronic hepatic encephalopathy in cirrhosis remains
      unknown. METHODS: Liver cirrhosis was induced by bile-duct ligation (BDL) in male
      Sprague-Dawley rats. Three weeks after BDL, rats were randomized to receive
      either tap water (control) or 0.04% methimazole in drinking water for 3 weeks. At
      the end of 6 weeks after BDL, severity of encephalopathy was assessed by the Opto
      Varimex animal activity meter and hemodynamic parameters were measured. Blood
      samples were collected for determination of thyroid stimulating hormone, ammonia
      and liver biochemistry. RESULTS: The heart rate of the methimazole-treated group
      was significantly lower than that of the control group (p = 0.015), whereas there
      were no differences in the mean arterial pressure and portal pressure. The total
      amount of movements were significantly increased in the methimazole group (p =
      0.029). Plasma levels of ammonia, aspartate aminotransferase and alkaline
      phosphatase were significantly lower (p = 0.01) and thyroid stimulating hormone
      significantly higher (p = 0.035) in the methimazole group. CONCLUSION: Chronic
      methimazole treatment alleviates hepatic encephalopathy and liver damage in rats
      with BDL-induced hepatic cirrhosis.

PMID- 17182350
TI  - Screening for platelet antibodies in adult idiopathic thrombocytopenic purpura: a
      comparative study using solid phase red cell adherence assay and flow cytometry.
AB  - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder
      caused by antiplatelet autoantibodies. In this study, we compared 2 methods for
      screening serum platelet antibodies in patients with ITP. METHODS: A total of 44
      adult patients were clinically classified with ITP. We used 2 indirect tests to
      detect human leukocyte antigen antibodies and/or platelet-specific antibodies in
      their sera. In method I, we used solid phase red cell adherence (SPRCA) assay. In
      method II, by flow cytometry, platelets from plateletpheresis components were
      used as target cells, and fluorescein isothiocyanate-conjugated sheep anti-human
      IgG Fc was used as the staining reagent. Positive results were defined as any
      test with the percentage of fluorescence exceeding the reference range by 3% or
      more in method II. Direct tests detecting platelet-associated IgG on platelets of
      patients with ITP were done by flow cytometry. RESULTS: Serum specimens from 44
      adult patients with ITP (28 female, 16 male) were tested. SPRCA assay could only
      detect platelet antibodies in 22 patients (50%). By method II, 31 serum specimens
      (70.5%) yielded positive results. There was a difference between the results of
      the SPRCA test and method II, with a high degree of significance (p < 0.001) by
      the McNemar test. No significant difference in platelet counts was observed for
      patients with and without discernible platelet antibodies by SPRCA assay (p =
      0.90). The direct test was positive in 12 patients (66.7%) out of 18 ITP patients
      tested. CONCLUSION: Flow cytometry is more sensitive than SPRCA assay for
      detecting platelet antibodies. Detection of platelet antibodies is useful in
      explaining the immune mechanism and platelet transfusion refractoriness in ITP.

PMID- 17182351
TI  - Craniofacial vascular malformations in Wyburn-Mason syndrome.
AB  - BACKGROUND: Wyburn-Mason syndrome (WMS) is a rare syndrome associated with
      multiple arteriovenous malformations (AVMs) involving the orbit, brain and/or
      face. The purpose of this study was to analyze the imaging spectrums of
      craniofacial vascular malformations in 14 patients with WMS. METHODS: The medical
      records of 14 patients with the diagnosis of WMS who underwent neuroimaging
      studies (computed tomography [CT], 8; magnetic resonance imaging [MRI], 12;
      conventional angiography, 14) were reviewed, emphasizing the location, extension
      and type of facial, orbital and brain vascular malformations. Complete WMS was
      defined as vascular malformations involving all the 3 zones of the face, orbit
      and brain, while partial WMS was considered as vascular malformation distributed
      in 2 zones. RESULTS: The craniofacial vascular malformations were confined on the
      left side in 7 patients, 2 were found on the right side, while the remaining
      other 5 patients had midline brain AVMs involving both sides. All but 1 of these
      14 patients had orbital and/or brain AVMs; facial vascular malformations were
      documented in 5 patients. The most common site of involvement was the optic nerve
      (n = 12), followed by the retina (n = 10), optic chiasma/hypothalamus (n = 9),
      thalamus (n = 7), basal ganglion (n = 5), midbrain (n = 2), occipital lobe (n =
      1), temporo-occipital lobe (n = 1) and fronto-temporo-parieto-occipital lobe (n =
      1). The complete form of WMS was found in 2 patients and the partial form in 12.
      CT, MRI and conventional angiography have the capacity to demonstrate the extent
      of intracranial AVMs. However, MRI is superior to both CT and angiography for
      detecting the size, extent of AVMs and the effects of AVMs on adjacent brain.
      Conventional angiography is superior to both CT and MRI in determining the
      detailed angioarchitecture of AVMs. CONCLUSION: WMS has a wide spectrum of
      multiple AVMs involving unilateral or bilateral craniofacial regions. The most
      common involved site is the orbit, followed by the brain. WMS should be
      considered in patients with ocular AVMs associated with brain AVMs.

PMID- 17182352
TI  - Posterolateral lumbar spinal fusion with autogenous bone chips from laminectomy
      extended with OsteoSet.
AB  - BACKGROUND: This study was conducted to evaluate posterolateral lumbar fusion
      with autogenous corticocancellous bone chips from the laminae and spinous
      processes extended with OsteoSet instead of cancellous bone from the iliac crest.
      METHODS: A total of 124 patients who underwent posterior decompression and
      posterolateral fusion with instrumentation between May 2001 and December 2003
      were analyzed retrospectively. The study population comprised 49 males and 75
      females with a mean age of 66 +/- 9.5 years. In all the patients,
      corticocancellous bone chips from laminectomy and OsteoSet were used as the graft
      material. There was no cancellous bone harvested from the iliac crest. The follow
      up period was 28 +/- 7.1 months. RESULTS: The overall union rate was 91%, and the
      average union time was 3.9 months. There were 3 complications, including 2
      patients with dura tear, and 1 with deep infection. At the final follow-up, the
      good and excellent results were up to 83.9%. CONCLUSION: Graft material from
      laminae and spinous processes extended with OsteoSet is reliable and effective
      enough to replace the graft from the posterior iliac crest.

PMID- 17182353
TI  - Hemorrhagic transformation of stroke secondary to spontaneous internal carotid
      artery dissection.
AB  - The clinical course of patients with hemorrhagic transformation in stroke
      secondary to spontaneous cervical internal carotid artery dissection (ICAD) has
      not been elucidated. We report a 36-year-old man with presentation of headache
      and subsequent left hemiparesis. Magnetic resonance imaging disclosed right ICAD
      with nearly complete occlusion of the right distal internal carotid artery and
      infarction over the right basal ganglion with hemorrhagic transformation in its
      central area. Hemorrhagic transformation can develop early in ICAD patients
      without preceding treatment with antithrombotic agents. Clinicians are urged to
      use antithrombotic agents with caution in patients with spontaneous ICAD with
      ischemic stroke because early hemorrhagic transformation may also be present.
      Possible pathomechanisms and treatment strategies are also discussed.

PMID- 17182354
TI  - Methylphenidate (Ritalin)-associated cataract and glaucoma.
AB  - Methylphenidate hydrochloride (Ritalin) is the drug of choice for attention
      deficit hyperactivity disorder (ADHD). However, an association of Ritalin with
      glaucoma has been reported. We report a case of Ritalin-associated cataract and
      glaucoma. A 10-year-old boy was diagnosed with ADHD and had received
      methylphenidate hydrochloride, 60 mg/day for 2 years. He presented with blurred
      vision. Best-corrected visual acuity was 6/60 in both eyes. Ocular examinations
      revealed intraocular pressure (IOP) of 30 mmHg under medication, dense posterior
      subcapsular opacity of lens, pale disc with advanced cupping, and marked
      constriction of visual field. Despite maximal anti-glaucomatous medication, IOP
      still could not be controlled. The patient then received combined cataract and
      glaucoma surgery. Visual acuity improved and IOP was within normal limits in both
      eyes postoperatively. Large dose of methylphenidate may cause cataract and
      glaucoma. The mechanism remains unclear. Doctors should be aware of the possible
      ocular side effects of methylphenidate.

PMID- 17182355
TI  - Vestibular rehabilitation in a patient with whiplash-associated disorders.
AB  - Whiplash-associated disorders are characterized by multiple physical complaints
      after a flexion-extension trauma to the neck. They are difficult to treat, and
      they often result in great impact on the patient's quality of life. In this
      paper, the comprehensive treatment of a patient with whiplash-associated
      disorders is presented. The purpose is to highlight the importance of accurate
      diagnosis and appropriate treatment plans to improve patients' quality of life.
      This 23-year-old woman experienced a traffic accident which caused severely
      painful neck disability, numbness over bilateral upper limbs, dizziness, double
      vision and loss of balance. Among these symptoms, dizziness was the problem that
      bothered the patient most. She received a comprehensive rehabilitation program
      including physical modalities, trigger point injections for relief of pain, as
      well as a vestibular rehabilitation program, which included exercises challenging
      and improving her balance function, head-eye coordination exercise, visual-ocular
      control exercise and sensory substitution-promoting exercises. She resumed her
      previous full-time work after 3 weeks of treatment. This successfully treated
      case illustrates the importance of correct diagnosis and appropriate treatment
      for patients who suffer from whiplash-associated disorders.

PMID- 17182356
TI  - Participation of Runx2 in mandibular condylar cartilage development.
AB  - OBJECTIVE: The purpose of this study was to investigate the expression pattern of
      Runx2 in mandibular condylar cartilage, a type of secondary cartilage. METHODS:
      Mandibular condyle of ddY mice were fixed from embryonic day 14 (E14) through
      just after birth (equivalent to E19). Samples were cut into 4 micro m serial
      sections through the central area of the mandibular condyle at the sagittal
      plane. Serial sections were examined using histological, immunohistochemical
      (IHC) and in situ hybridization (ISH) techniques. RESULTS: There are no
      developmental features of mandibular condyle. At the distal upper portion of
      developmental mandibular bone, mesenchymal cell proliferation and condensation
      without metacholomatic reaction to Toluidine blue (TB) were seen at E14. At E15,
      mandibular condylar cartilage was clearly evident, as TB metacholomasia. In IHC
      specimens at E14, expression of Runx2 peptide was observed in the nuclei and the
      cytoplasms cells of coagulating mesenchymal cells, both in the cytoplasm and
      nucleus. After E17, Runx2 appeared in the cells of the condylar cartilage sheath.
      In ISH examination at E14 and E15, expressions of Runx2 mRNA appeared in the
      cytoplasms of proliferating chondrocytes. From E16 to E18, Runx2 mRNA was
      detected throughout almost all cytoplasm in all layers. CONCLUSION: These IHC and
      ISH results suggest that Runx2 plays an essential role for mandibular condylar
      cartilage development, especially that Runx2 is essential for the onset of
      secondary cartilage differentiation.

PMID- 17182357
TI  - Multifocal epithelioid hemangioendothelioma: case report of a clinical
      chamaeleon.
AB  - Epithelioid hemangioendothelioma is an extremely rare vascular bone tumor with a
      slow growth and poor prognosis. The term was designed to describe neoplasms that
      had an appearance in between hemangiomas and sarcomas. Various synonyms for
      epithelioid hemangioendothelioma are used clinically: low grade anaplastic
      angiosarcoma, cellular hemangioma, histiocytoid hemangioma and angioendothelioma.
      However, it represents 1% of all vascular neoplasms and is locally aggressive. We
      report the course of disease of a 47-year-old man who presented to our clinic
      with unspecific abdominal and back pain. Radiological findings revealed multiple
      lesions in the spine as well as liver and spleen involvement. Tumor histology of
      the bone and liver biopsies confirmed the diagnosis of epithelioid
      hemangioendothelioma. Although treatment was initiated with thalidomide, the
      patient developed multiple organ dysfunction syndrome (MODS) and succumbed to his
      disease. This case report may contribute to the data on clinical findings and
      natural history of this rare tumor.

PMID- 17182358
TI  - Liver transplantation for hepatocellular carcinoma in patients beyond the Milan
      but within the UCSF criteria.
AB  - AIM: Liver transplantation (LT) is the best therapy for early hepatocellular
      carcinoma (HCC) in cirrhosis. Whereas the Milan criteria are routinely applied,
      the University of California San Francisco (UCSF) criteria are occasionally
      considered in large-volume transplant centers. Poor information is available
      about the real "gain" in patients' outcome when extending the listing criteria
      from Milan to UCSF. PATIENTS AND METHODS: Out of 100 patients transplanted for
      HCC at our center, 4 patients exceeding the Milan but meeting the UCSF criteria
      were identified. Data of these patients were analysed for the purposes of this
      study. RESULTS: Three of them are currently alive after a median follow up of 57
      months. One patient died 20 months post-transplant as a result of complications
      from hepatitis. Of the three who are alive, one underwent surgery for HCC
      recurrence 81 months post transplant. The remaining two have no evidence of tumor
      56 and 57 months post transplant, respectively. CONCLUSION: Our results, as well
      as the reviewed literature, showed that only a small percentage of transplanted
      HCC patients can be classified as "beyond Milan-within UCSF". These patients seem
      to have acceptable overall, as well as recurrence free survivals. Large-volume
      patients' series, intention- to-treat analysis based on the radiological findings
      and multi-center prospective studies are required, in order to further explore
      the outcome of patients "beyond Milan-within UCSF" criteria and in order to
      better define the risk/benefit ratio of a potential expansion of the current
      listing criteria.

PMID- 17182359
TI  - Analysis of biodegradation of copolymer dermis substitutes in the dorsal skinfold
      chamber of balb/c mice.
AB  - PEGT/PBT-block-copolymer dermis substitutes were inserted into dorsal skinfold
      chambers of balb/c mice (n=36). Scaffolding matrices with 3 different pore
      diameters (pore diameter: <75 micro m, 75-212 micro m and 250-300 micro m) were
      analyzed on days 7, 14, and 21 post implantation by scanning electron and light
      microscopy. The quantification of matrix fragmentation was performed using image
      analytical software analySIS(R). The fragmentation rate in scaffolding matrices
      with a pore size of < 75 micro m was observed to be higher than in matrices of
      larger pore sizes. Image-analytical evaluation over 21 days revealed a reduction
      of the copolymer matrix by approximately 32% for the <75 micro m matrices, 23%
      for the 75-212 micro m matrices and 18% for the matrices, where pore size ranged
      between 250 micro m and 300 micro m. Twenty-one days after implantation, the
      matrix pores of 75-212 micro m and 250-300 micro m scaffolds were totally filled
      by vascularized fibrous tissue. Contrarily, an increased formation of foreign
      body giant cells was observed in matrices with pore size <75 micro m. The pore
      size of the scaffolding PEGT/PBT dermis substitutes affects their degradative
      behaviour in vivo.

PMID- 17182360
TI  - Analysis of the Candida albicans - specific T-cell response and oropharyngeal
      Candida colonization in a cohort of HIV-1-infected patients.
AB  - To investigate Candida epidemiology and immunologic correlates of protection in
      HIV-1 infected patients, we analyzed oral Candida colonization in correlation to
      the Candida-specific T-cell response measured by g-IFN ELISPOT using different
      Candida (C.) albicans strains. In 16/46 patients (13 asymptomatic, 3 with oral
      thrush), but in 0/28 controls, Candida (13 C. albicans, 1 C. lusitaniae, 1 C.
      krusei, 1 C. parapsilosis) was isolated. Candida specific T-cells were detected
      more frequently in controls (20/28) than in HIV-1+ subjects (16/46, p= 0.03). We
      observed a significant association of higher CD4 cell numbers with both detection
      of Candida specific T-cells and lack of oral Candida colonization, but there was
      no significant correlation of oral Candida colonization to the detection of
      Candida specific T-cells, viral load or antiretroviral therapy. Thus, local
      mucosal immunity seems to be more important in the pathogenesis of Candida
      colonization than circulating Candida specific T-cells. The pathogenic C.
      albicans strain K24122 was less frequently recognized by patients (6/46) than the
      laboratory adapted strain SC5314 (14/46, p= 0.03), whereas a similar recognition
      of both strains was observed in healthy controls. This indicates an impaired
      Candida-specific T-cell repertoire in HIV+ patients that could increase the risk
      of immune evasion by C. albicans.

PMID- 17182361
TI  - Randomised and non-randomised prospective controlled cohort studies in matched
      pair design for the long-term therapy of breast cancer patients with a mistletoe
      preparation (Iscador): a re-analysis.
AB  - OBJECTIVE: Expanded presentation and re-analysis of previously published data of
      randomized and non-randomized studies on mistletoe therapy with breast cancer
      patients [3, 4]. The main question is: Does a re-analysis confirm the previously
      reported effects of prolonging the survival of patients with breast cancer under
      long-term application of a complementary/anthroposophic therapy with the European
      mistletoe preparation Iscador? DATA SOURCES: (1) Randomised matched-pairs study:
      Breast cancer patients with only lymphatic metastases (17 pairs) that had never
      used mistletoe therapy were matched for several prognostic factors. By paired
      random allocation, one patient of a pair received a suggestion of mistletoe
      therapy to be applied by the attending physician. (2) Non-randomised matched
      pairs studies: Patients that had already received mistletoe (Iscador) therapy
      were matched to control patients from the same pool using the same prognostic
      criteria. Three groups were recruited by this procedure: breast cancer with local
      recurrences and no metastases (42 pairs), breast cancer with only lymphatic
      metastases (55 pairs), and breast cancer with distant metastases (83 pairs).
      ANALYSIS: Cox proportional hazard models and sensitivity analyses based on
      subsets of the original data sets according to strict or lose application of the
      matching criteria. RESULTS: The results of this re-analysis are consistent with
      the earlier results, even when comparing different methods and subsets. In the
      randomised study, the effect of long-term Iscador therapy on overall survival is
      significantly in favour of the Iscador therapy: Estimate of the median difference
      and 95 % confidence interval in years 2.5 (0.83, 4.50). The results for the non
      randomised studies were also in favour of the Iscador therapy: Breast cancer with
      local recurrences and no metastases: estimate of hazard ratio and 95 % confidence
      interval 0.52 (0.23, 1.17); breast cancer with lymphatic metastases: 0.27 (0.15,
      0.50); breast cancer with distant metastases: 0.53 (0.32, 0.88). As a short-term
      effect of this therapy, psychosomatic self-regulation noticeably increases within
      3 months in the Iscador group in comparison to the control group in the
      randomised study: estimate of the median difference 0.90 (0, 1.75). CONCLUSION:
      The re-analysis demonstrates that the effects shown in the previously published
      data are consistent despite using different analytic methods and different
      subsets. Overall, the survival of patients receiving mistletoe treatment with
      Iscador is longer in these studies. In the short term, psychosomatic self
      regulation, as a measure of autonomous coping with the disease, rises more under
      Iscador therapy than under conventional therapy alone.

PMID- 17182362
TI  - Central action of a fixed Valerian-hops extract combination (Ze 91019) in freely
      moving rats.
AB  - Due to the electrochemical nature of the communication structure of the brain an
      intimate relationship between neurotransmitter activity on one side and field
      potentials (EEG) on the other side have been reported. From this it can be
      assumed that the electrical activity reflects the net effect of drug action. The
      influence of increasing doses of Ze 91019 on field potentials in chronically
      instrumented, freely moving rats was registered for 4 hours in order to test its
      action on the central nervous system. Doses of 200 mg and 250 mg valerian siccum
      extract (with additional 48 or 60 mg hop siccum extract) increased the spectral
      power in the delta, theta and alpha frequency bands of the frontal cortex
      suggestive of attenuated cholinergic transmission. Since adenosine administration
      into the basal forebrain also increases the low frequency activity in the frontal
      cortex it can be assumed that adenosine in the basal forebrain mediates these
      frequency changes by attenuating the frontal cholinergic system. Thus, Valerian
      and the fixed valerian hop extract combination Ze 91019 seems to cause this
      change of spectral power acting as an adenosine A1 receptor agonist. The results
      are therefore in line with the view that the fixed extract combination Ze 91019
      works as an adenosine agonist via inhibition of cholinergic transmission leading
      to sedation and sleep.

PMID- 17182363
TI  - Treatment procedures for anal fistulous cryptoglandular abscess--how to get the
      best results.
AB  - INTRODUCTION: Up to date anal fistulous cryptoglandular abscess is a subject of
      controversial scientific discussions and the number of medico legal cases dealing
      with treatment procedures is growing . In principal, there is a dispute whether
      it is reasonable to perform a primary fistulotomy at the time of abscess drainage
      or to wait for a secondary fistulotomy. The purpose of this study was to compare
      studies focussing on the treatment of anal fistulous abscess with regard to
      different treatment procedures, their outcome (recurrence, incontinence, follow
      up) and factors influencing outcome (primary or recurrent fistulous abscess,
      comorbidity, exclusion criteria, anaesthesia, microbiology, antibiotics, search
      for internal opening, classification). METHODS: A Medline search included the
      terms: fistulous abscess, anal abscess, horseshoe abscess, anorectal sepsis, and
      perianal infection/abscess. RESULTS: In 63 (1964-2004) studies we found 35
      different treatment methods: the most often used procedures were incision and
      drainage (I+D; n = 35) and incision and drainage and primary fistulotomy (I+D+pF;
      n = 23). Only in ten studies the treatment has been restricted for primary anal
      fistulous abscess; the remaining studies investigated primary and recurrent anal
      fistulous abscess. There was a considerable lack of information on morbidity,
      microbiology, and exclusion criteria. In only 16/63 studies patients were
      routinely diagnosed and treated under general anaesthesia. We found nine
      different classifications of fistulous abscess. There is a wide range of
      recurrence after different treatment procedures: up to 88% after I+D and 21%
      after I+D+pF. The incontinence rate after I+D ranged from 0-26%, after I+D+pF 0
      52%. However, in many studies there was no information on incontinence available.
      CONCLUSION: A true comparison of different treatment methods is not available.
      This is mainly due to either a lack of information on important factors
      influencing outcome, even unclear definitions in some instances. Recent
      randomized studies have been criticized for missing information and flaws in the
      randomization procedure. The choice of treatment, e.g., primary or secondary
      fistulotomy, depends on the clinical experience of the surgeon on duty, the
      hospital structure (staff, equipment, and anaesthesia), the patient's history and
      the local anatomical circumstances. On the basis of up to date knowledge there is
      no reason to condemn primary or secondary fistulotomy without more clinical
      studies and without knowing the individual situation.

PMID- 17182364
TI  - Consensus meeting on "Relevance of parenteral vitamin C in acute endothelial
      dependent pathophysiological conditions (EDPC)".
AB  - The 22 supersetnd Hohenheim Consensus Workshop took place in at the University of
      Stuttgart-Hohenheim. The subject of this conference was vitamin C and its role in
      the treatment of endothelial dysfunction. Scientists, who had published and
      reviewed scientific and regulatory papers on that topic were invited, among them
      basic researchers, toxicologists, clinicians and nutritionists. The participants
      were presented with eleven questions, which were discussed and answered at the
      workshop, with the aim of summarising the current state of knowledge. The
      explicatory text accompanying the short answers was produced and agreed on after
      the conference and was backed up by corresponding references. The therapeutic
      relevance of administration of the physiological antioxidant vitamin C in high
      parenteral doses in Endothelial Dependent Pathophysiological Conditions (EDPC)
      was discussed. Endothelial dysfunction is defined as including disturbed
      endothelial dependant relaxation of resistance vessels, breakdown of the
      microvascular endothelial barrier and/or loss of anti-adhesive function. It
      occurs in severe burn injury, intoxications, acute hyperglycemia, sepsis, trauma,
      and ischemic-reperfusion tissue injury and is induced by oxidative stress.
      Reduced plasma ascorbate levels are a hallmark of oxidative stress and occur in
      severe burns, sepsis, severe trauma, intoxication, chemotherapy/radiotherapy and
      organ transplantation. Vitamin C directly enhances the activity of nitric oxide
      synthase, the acyl CoA oxidase system and inhibits the actions of proinflammatory
      lipids. There is experimental evidence that parenteral high-dose vitamin C
      restores endothelial function in sepsis. In vitro, supraphysiological
      concentrations (> 1mM) of ascorbate restore nitric oxide bioavailability and
      endothelial function. Only parenterally, can enough vitamin C be administered to
      combat oxidative stress. There is no evidence that parenteral vitamin C exerts
      prooxidant effects in humans. Theoretical concerns in relation to competitive
      interactions between vitamin C and glucose cellular uptake are probably only
      relevant for oxidised vitamin C (dehydroascorbate).

PMID- 17182365
TI  - Differentiation between malignant and benign solitary pulmonary nodules with
      proton density weighted and ECG-gated magnetic resonance imaging.
AB  - OBJECTIVE: To estimate performance of MRI for differentiating malignant from
      benign solitary pulmonary nodules (SPN) using morphological characteristics.
      MATERIAL AND METHODS: MRI in 46 patients with SPN (mean diameter: 19 mm) was
      carried out on 1.0 Tesla scanner using ECG-gated, gradient echo sequence.
      Morphological signs of SPN were determined and compared with previously performed
      helical-CT, where final diagnosis served as reference with 52% frequency of
      malignancy. Furthermore, three observers evaluated all images. RESULTS:
      Significant differences between the two groups were found for nodules shape,
      margin, inhomogeneity and the vessel-sign in MRI, nodules shape, margin, the
      vessel-sign, and presence of spicules in CT. Using these signs, AUC were 0.746
      for MRI and 0.765 for CT. The mean sensitivity, specificity, and accuracy of
      observers for MRI/CT were 89%/95%, 42%/41%, 66%/68%, respectively. CONCLUSIONS:
      Despite discrepancies in morphologic appearance, no significant difference of
      accuracy between MRI and CT was determined. Further investigations are necessary
      to demonstrate the clinical use in combination with functional parameters,
      establishing MRI as a comprehensive diagnostic modality for SPN.

PMID- 17182366
TI  - Computation and modeling of the stone-growth related urinary depletion effect
      using "depletion V1.0".
AB  - PURPOSE: During metabolic evaluation stone patients often present with calculi in
      the urinary tract or are suffering from high frequent formation of small
      microliths passing routinely the urinary tract. These concrements are presumably
      in a state of continuous growth. Consequently, the concentrations of the
      lithogenic components in the voided urine must decrease. Thus, treatment schemes
      inevitably fail to focus on the true pathogenic urinary composition. Instead,
      they focus on underestimated concentrations. This can attain high clinical
      relevance. In recent publications, we introduced a complex physical approach and
      provided mathematical equations which can be solved analytically. However, to
      date, solving the equations with a pocket calculator remains cumbersome.
      MATERIALS AND METHODS: Depletion V1.0 was developed to integrate the calculation
      of the depletion effect into the daily treatment of stone patients. Minimum
      requirement for Depletion V1.0 is the Java 1.2 platform runtime environment,
      which is supported on nearly all operation systems including Linux, MacOS X, and
      Windows. The program can be used directly within a Java-compliant web browser
      (e.g. Firefox, Mozilla, Internet Explorer) or from the program's storage
      location. The implemented data base provides stone type relevant parameters. Data
      input is performed via an easy-to-handle graphical user interface. RESULTS:
      Results are given as values and interactive plots; computation and update of
      plots are performed in real time. Result sheets can be exported to platform
      independent EPS-format or printed out directly. CONCLUSIONS: Depletion V1.0
      enables the medical practitioner to obtain an improved interpretation of the
      stone patient's health status. As input, only one set of easy-to-achieve clinical
      standard parameters is required. The program will be available from the authors
      as freeware.

PMID- 17182367
TI  - Endocrinological markers for assessing hyperandrogenemia in women classified as
      having polycystic ovary syndrome (PCOS) according to the revised 2003 diagnostic
      criteria.
AB  - The aim of this study was to investigate whether free testosterone estimated by
      calculation from total testosterone and sex hormone-binding globulin or free
      androgen indexes were more appropriate markers for assessing hyperandrogenemia in
      patients with polycystic ovary syndrome (PCOS). 107 Caucasian women were
      presented at our Division of Gynecological Endocrinology and Reproductive
      Medicine because of their infertility and hirsutism. Hirsutism was quantitatively
      assessed using a modified Ferriman-Gallwey score; oligo-ovulation or/and
      anovulation were assessed; polycystic ovaries were assessed; afterwards women
      were classified as having PCOS according to the revised 2003 consensus on
      diagnostic criteria for PCOS or classified as controls; endocrinological
      parameters were assessed using commercial immunoassays or were calculated. 50
      women were classified as having PCOS; 57 women were classified as controls
      because they did not fulfill the criteria of PCOS. Calculated free and
      bioavailable testosterone, FAI, total testosterone, free testosterone assessed by
      immunoassay and DHEAS were significantly increased in women classified as having
      PCOS. All endocrinological markers for assessing hyperandrogenemia were elevated
      in the PCOS group regardless if they were assessed using commercial immunoassays
      or were calculated. Calculated values showed no diagnostic advantage in this
      study.

PMID- 17182368
TI  - Benign symmetric lipomatosis with axonal neuropathy and abnormalities in specific
      mitochondrial tRNA regions.
AB  - Benign symmetric lipomatosis, also called Madelung's disease, is characterized by
      lipomata and fatty infiltrations. Involvement of the nervous system has
      occasionally been described, mitochondrial dysfunctions have been suggested. We
      report a 55 year old male suffering from benign symmetric lipomatosis with
      associated axonal neuropathy and hyperlipoproteinemia. He showed a remarkable
      phenotype of neuropathy i.e. no sensory disturbance, ubiquitous fasciculations
      and muscle cramps, furthermore reduced COX activity and abnormalities in specific
      mitochondrial tRNA regions.

PMID- 17182369
TI  - TP63 gene in stress response and carcinogenesis: a broader role than expected.
AB  - The TP63 gene is a member of the TP53 gene family. In contrast with TP53, this
      gene is not frequently inactivated by mutation in cancer. Initial experiments
      with disrupted TP63 have allowed specifying p63 protein a role in the regulation
      of differentiation and morphogenesis in epithelial and mesenchymal tissues.
      Nevertheless, there is growing evidence that p63 is also involved in oncogenesis
      through several mechanisms. Indeed, amplification of TP63 is detected in about
      25% of squamous cell carcinomas of lung, head and neck and oesophagus. This
      results in overexpression of a truncated form of p63 (DeltaNp63) that may
      counteract growth suppression induced by full length p63 (TAp63), as well as by
      the other family members, p53 and TAp73. Moreover, mice heterozygous for TP63
      develop spontaneous tumours. Whereas p53 plays a major role in response to
      numerous DNA-damaging agents, the involvement of p63 in this process is not well
      documented. Nevertheless, several groups recently reported that TAp63 can induce
      cell cycle arrest and apoptosis in DNA-damaged cells, alone or in synergy with
      chemotherapeutic agents, and thus appears as a chemosensitivity factor. Overall,
      in addition to non-redundant, specific functions in differentiation and
      morphogenesis, p63 appears to exert biological functions similar to those of p53
      and to take a growing place in oncogenesis and modulation of responses to anti
      cancer therapy.

PMID- 17182370
TI  - [Nobel Price in medicine 2006].

PMID- 17182371
TI  - [Imaging and cancers].

PMID- 17182372
TI  - [Retroperitoneal sarcomas imaging].
AB  - Retroperitoneal sarcomas are rare neoplasms. The aim of this article is to expose
      imaging protocols and useful radiological signs, to show the core biopsy
      technique for diagnosis, to precise imaging key points before treatment and for
      survey.

PMID- 17182373
TI  - [Multimodalities imaging for target volume definition in radiotherapy].
AB  - Modern radiotherapy delivery nowadays relies on tridimensional, conformal
      techniques. The aim is to better target the tumor while decreasing the dose
      administered to surrounding normal tissues. Gold standard imaging modality
      remains computed-tomography (CT) scanner. However, the intrinsic lack of contrast
      between soft tissues leads to high variabilities in target definition. The risks
      are : a geographical miss with tumor underirradiation on the one hand, and a
      tumor overestimation with undue normal tissues irradiation on the other hand.
      Alternative imaging modalities like magnetic resonance imaging and functional
      positron emission tomography could theoretically overcome the lack of soft
      tissues contrast of CT. However, the fusion of the different imaging modalities
      images requires the use of sophisticated computer algorithms. We will briefly
      review them. We will then review the different clinical results reported with
      multi-modalities imaging for tumors of the head, neck, lung, esophagus, cervix
      and lymphomas. Finally, we will briefly give practical recommendations for multi
      modality imaging in radiotherapy treatment planning process.

PMID- 17182374
TI  - [Imaging strategy for staging and follow-up of endocrine tumors].
AB  - Endocrine tumours constitute a homogeneous network of tumours scattered in the
      body and characterized by several common features including their capacity to
      secrete hormones, their association as part of inherited syndrome and their
      ability to be explored either by functioning imaging than by morphological
      imaging. However, they have a broad and initially misleading clinical spectrum.
      Staging of these tumours must be multidisciplinary with the association of
      primary tumour exploration, staging and follow-up. It also contribute to the
      screening of complications due to hormonal secretions, the exploration of
      inherited syndromes and a second cancer diagnosis. First we review the technical
      characteristics of each imaging modality including morphological imaging
      (computed tomography, magnetic resonance imaging), metabolic imaging
      (somatostatin receptors scintigraphy, PET-scan), endoscopy and vascular imaging.
      Then we review for each endocrine tumour localization and clinical presentation,
      the imaging strategy as well as the most common morphological and functional
      features.

PMID- 17182375
TI  - [Evaluation of the therapeutic response: role of isotopic imaging].
AB  - In comparison with conventional imaging, nuclear medicine offers an original
      metabolic approach for the assessment of the therapeutic response. Gallium 67,
      thallium 201, technetium 99m-labeled sestamibi and diphosphonates can be
      performed for therapeutic response assessment in lymphoma, brain and breast
      tumours, sarcoma, or bone metastasis. PET-CT facilities are now easily available
      in France and are ready to provide a new and accurate tool in oncology, specially
      for therapeutic evaluation. The procedure consists in the injection of fluor-18
      fluoro-deoxyglucose (18FDG), an analogue of glucose, followed by a PET then a CT
      acquisition for FDG uptake abnormalities location. Therapeutic response is
      assessed by a decrease of 18FDG tumoral uptake between two consecutive studies.
      Methodology and interpretation criteria have been recently defined in
      international guidelines. 18FDG-PET-CT seems to be a valuable tool for
      therapeutic response assessment of patients with Hodgkin or non Hodgkin malignant
      lymphoma. Promising preliminary results have been recently published for lung,
      gastro-intestinal and head and neck cancers. PET-CT could also be able to predict
      the therapeutic response after the first courses of chemotherapy, allowing an
      early treatment optimization. Finally, new PET agents pave the way for molecular
      imaging with promising results in gene therapy and targeted treatment in
      oncology.

PMID- 17182376
TI  - [Interest of imaging for the monitoring of a treated cancer: simplified use of
      likelyhood ratio. The example of soft tissue tumor].
AB  - Systematic follow-up of patients after initial treatment of cancer is stressful
      with heavy cost. The aim of such follow-up is to detect asymptomatic lesions in
      viewing to increase global survival and quality of life. For an individual
      patient, the issue of cancer recurrence is a binary event. However, when
      developing surveillance strategies for large groups of patients, knowledge of the
      risks (tumor biology, natural history of the disease), the benefits (potential
      efficacy of salvage therapy) and diagnosis test performances is necessary to
      formulate a rationale and resource effective follow-up algorithm. The
      Bayes'nomogram is useful to assess diagnosis test. Soft tissue sarcoma is a
      example of such demonstration.

PMID- 17182377
TI  - [Current events about echography in 2006: position of the ultrasound functional
      imaging for the early evaluation of targeted therapeutics].
AB  - The early and functional evaluation of new treatments in oncology is a main goal.
      At present, technical advances in Doppler ultrasonography allow the detection of
      neovascularization for superficial and deep malignant tumours in order to
      evaluate the efficiency of new treatments such as antiangiogenic molecules.
      Contrast agents injection improves the efficiency of this technique and
      developments of perfusion softwares optimize this detection. Slow flows in tumour
      microvessels can be detected. Treatment response can be early predicted based on
      changes in the vascularization before volume modification. The availability of
      quantification softwares operating from the raw data before their compression for
      video display affords one and objective quantification of the contrast agent
      uptake.

PMID- 17182378
TI  - [Epithelial advanced ovarian carcinoma in the central region of Tunisia:
      therapeutic results and prognostic factors on 104 patients].
AB  - Between 1994 and 2004, 104 patients with epithelial advanced ovarian cancer were
      treated in the central region of Tunisia (81 stage III and 23 stage IV). Average
      age of patients was 54 years. Primary surgery was optimal (residue < 2 cm) in 40
      cases (38,5 % of patients). Fifty nine patients were treated with neo adjuvant
      chemotherapy based on platinum, associated to paclitaxel in 19 % of cases.
      Interval debulking surgery interested 30 patients and was optimal in 66,7 % of
      cases. Global survive was 57 % at 2 years and 27 % at 5 years. Survival rate for
      patients treated with optimal debulking surgery was similar to that of those
      treated with initial optimal surgery. Prognostic factors for a better survive
      were : age < 40 years (p < 0,05), stage III (p < 0,01), a normal level of CA125
      after surgery (p < 0,01), primary optimal initial surgery (p < 0,02) and response
      to neoadjuvant chemotherapy (p < 0,01). Prognosis of ovarian carcinoma is worse
      in Tunisia as like as in the world. In case of extensive tumor, the neoadjuvant
      chemotherapy before interval debulking surgery permits to improve survive and
      quality of life in some patients.

PMID- 17182379
TI  - [25th meeting of the European Society for Therapeutic Radiology and Oncology
      (ESTRO)].

PMID- 17182380
TI  - Behaviour and fate of tetracycline in river and wetland waters on the Canadian
      Northern Great Plains.
AB  - Very little is known about the factors affecting the behaviour, degradation and
      persistence of tetracycline in sensitive Prairie freshwater aquatic systems in
      Canada. Reported are results of studies conducted for the first time of
      tetracycline behaviour in Prairie river and wetland waters. For comparison,
      studies were also conducted using distilled water as a control. Different amounts
      of spiked tetracycline (0, 50 and 80 percent) was adsorbed by distilled, river
      and wetland water, respectively. These different amounts are likely due to the
      differences in the matrixes of the three waters. In wetland water, the addition
      of EDTA generally promoted the release of tetracycline indicating that a portion
      of the tetracycline was bound to metal ions. Decreasing the pH of the wetland
      water led to increased adsorption of tetracycline suggesting either that
      tetracycline epimerizes or binds, by hydrogen bonding, to acidic portions of
      organic material in the water. However, in wetland water, a significant portion
      of the spiked tetracycline (approximately =50%) was irreversibly bound to the
      water matrix and was not released by adding EDTA and/or by varying the pH. In
      laboratory experiments, the t1/2 of "free-form" tetracycline exposed to light
      (L+) in non-sterile waters was 32, 2 and 3 days in distilled, river and wetland
      water respectively, while in waters with no light exposure (L-), they were 83, 18
      and 13 days. Similarly, t1/2 of tetracycline in L+ sterile waters treatments was
      9, 1 and 1 day for distilled, river and wetland water, respectively, and 18, 11
      and 7 days in the L-. In the experiment conducted in natural sunlight,
      tetracycline t1/2 in the presence of ultraviolet radiation (UV) treatments was
      26, 17 and 18 min in distilled, river and wetland water and 39, 28 and 32 min in
      the absence of UV treatment. The combination of the effects of matrixes of the
      water, light and UV radiation therefore play a significant role in catalyzing the
      removal of tetracycline from different Prairie waters. In deep waters and in
      systems where sunlight is highly attenuated, the effects of light on tetracycline
      may be considerably reduced.

PMID- 17182381
TI  - Comparison of polycyclic aromatic hydrocarbons in sediments from the Songhuajiang
      River (China) during different sampling seasons.
AB  - The Songhuajiang River watershed is the important industrial and foodstuff base
      in the northeast part of China. However, the increasing population, industrial
      and agricultural activities around the Songhuajiang River lead to the
      introduction of contaminants and the possibility of polluting the river. This
      investigation represents an extensive study of the spatial and temporal
      distribution of polycyclic aromatic hydrocarbons (PAHs) in the sediment samples
      collected from the Songhuajing River in flood season (August, 2005) and icebound
      season (December, 2005) by using the gas chromatography-mass spectrometry (GC/MS)
      analyses. In flood season, the total PAHs concentrations in sediments ranged from
      84.44 ng g-1 to 14938.73 ng g-1, with average concentration of 2430.37 ng g-1. In
      icebound season, the total PAHs concentrations in sediments ranged from 23.61 ng
      g-1 to 15310.25 ng g-1, with average concentration of 1825.60 ng g-1. Compared to
      the concentration of PAHs between central sediment and riverbank-exposed sediment
      at some stations, the concentration in exposed sediment was higher than that in
      the central sediment in the upstream of river. It was also observed that the
      concentration of PAHs in flood season was higher than that in icebound season.
      The level of PAHs in the sediments of Songhua River was higher in comparison with
      values reported from other river and marine systems in the world. The most
      contaminated sediment samples were found in the upstream area of Songhuajiang
      River located near Jilin petrochemical industrial company for both flood and
      icebound seasons. The 4-6 ring PAHs were dominated in sediments due to their
      higher persistence. There was positive correlation between total PAHs
      concentration in sediment samples and TOC or LOI (r = 0.62 and r = 0.58, P <
      0.01, n = 31). The calculated ratio of selected PAH and principal component
      analysis (PCA) suggests the contamination source of PAHs were combined inputs of
      pyrolytic and petrogenic contamination, due to the discharge from municipal and
      industrial wastewater runoff and atmospheric fallout.

PMID- 17182382
TI  - Air-water partitioning equilibrium of tetrahydrofuran in an activated sludge
      system.
AB  - This study evaluate the effect of liquid tetrahydrofuran (THF) concentration and
      biomass content on the THF air-water partitioning equilibrium for a simulated
      activated sludge system. The equilibrium of the partition at the air-water
      interface is given by a partitioning coefficient (pc) = Cg*/CL, where Cg* denotes
      the gaseous concentration in equilibrium with the aqueous THF concentration (CL).
      Variations of pc with CL in static pure water are evaluated, and high solubility
      of THF in water caused pc values to drop as the CL increased from 29.81 +/- 0.16
      to 297.75 +/- 2.28 mg/L at a constant temperature of 27 degrees C. Meanwhile, the
      hydrophilicity of THF in water induced a biomass effect, causing pc to increase
      in the activated sludge liquor. Due to the co-effect of liquid THF concentration
      and biomass content, the pc values of THF for the liquor of mixed liquid
      suspended solid (MLSS) concentration = 1220 +/- 86 mg/L and THF CL = 242.91 +/-
      69.09 mg/L increased 22.5% compared to those in the pure agitated water. The
      biomass effect on pc of hydrophilic VOC increases the gaseous VOC emission rate
      from the activated sludge facilities.

PMID- 17182383
TI  - Thermodynamical and quantum-chemical characterization and chemometrical selection
      of representative congeners of trans-chloroazoxybenzene.
AB  - Polychlorinated trans-azoxybenzenes (PCt-AOBs) consist a group of 399
      theoretically possible congeners, which are toxicologically and environmentally
      relevant compounds. Some of PCt-AOBs have been identified as by-side impurity in
      technical grade 3,4-dichloroaniline (3,4-DCA), and also in derived of this
      chemical pesticides such as Diuron, Linuron or Propanil. In this study 31 quantum
      chemical descriptors were in silico generated and used to characterize all 399
      PCt-AOBs. Further, the basic thermodynamic and quantum-chemical property data
      matrix of PCt-AOBs made was interpreted with an aid of the Principal Component
      Analysis (PCA). The PCA of these data matrix created a three-dimensional model
      that explained 77.31% (63.79% + 8.87% + 4.65%) of the total variance.
      Polarizability, molecular weight, logarithm of the n-octanol/water partition
      coefficient, molecular refraction, valence molecular index, kappa index,
      molecular connectivity index, thermal capacity and entropy were the best
      positively correlated descriptors, which all are connected with molecular shape
      and size of the molecules. They all are explained by the first principal
      component (PC1), while energy of the highest occupied molecular orbital, Gibbs
      free energy in gas phase, standard heat of formation, the total particle energy
      and thermal energy were negatively correlated. The PC2 depended on polarizability
      vector Z and energy of the lowest unoccupied molecular orbital, while the PC3 was
      negatively impacted by the most positive partial charge on atoms. The congeners
      of trans-PCAOBs substituted with chlorine at positions 2' (ortho position) are
      non-planar. 119 Congeners of trans-chloroazoxybenzene (Ct-AOB) could be
      classified amongst stereoisomers (analogues) to highly toxic and environmentally
      persistent 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Data obtained
      after PCA were further used to create Fractional Factorial Design of PCt-AOBs and
      eight congeners, i.e., 2',3'-DiCt-AOB (no. 11), 2,2',5-TrCt-AOB (no. 32), 3',4'
      DiCt-AOB (no. 24), 2,4,5-TrCt-AOB (no. 58), 2,2',3,4',5,5'-HeCt-AOB (no. 271),
      2,2',3',4',5,5',6'-HpCt-AOB (no. 360), 2,3,3',4,4',5',6-HpCt-AOB (no. 364) and
      2,2',3,3',4',5',6'-HpCt-AOB (no. 337), which probably are the best describers of
      the whole group, could be assigned.

PMID- 17182384
TI  - The capacity of the Gunderboom in Mamaroneck Harbor on the reduction of E. coli
      and coliform bacteria from water and soft-shelled clams (Mya arenaria).
AB  - Harbor Island Park of Mamaroneck Harbor is one of the beaches that has been
      frequently closed to the public due to unsanitary swimming conditions. In 2002, a
      Gunderboom BPS (Beach Protection System) was reinstalled in Harbor Island Park to
      lower bacterial levels in swimming areas. The first Gunderboom had been destroyed
      by an oil spill several years before. The current Gunderboom is an 800 foot
      curtain made of a treated polypropylene/polyester fabric and the company claims a
      99.1% coliform reduction with its use. In this study, water inside and outside
      the Gunderboom was tested weekly from June to August 2005, and bi-weekly from
      September to December 2005. Coliscan Membrane Filtration plates were used to
      recover the relative amounts of Escherichia coli and coliform bacteria from the
      water. Soft-shelled clams (Mya arenaria) living in both these areas were also
      tested for their E. coli and coliform bacteria level using 3M Petrifilm plates.
      Water was also tested from Hudson Park in New Rochelle, a frequently closed beach
      due to high levels of coliform bacteria, as well as from Read Sanctuary in Rye, a
      "pristine" beach. Our results showed the amount of E. coli and coliform bacteria
      recovered from the water inside the Gunderboom were significantly lower (P <
      0.05) compared to outside the Gunderboom and Hudson Park. There was 81.9%
      reduction in E. coli and 51.6% reduction in coliform bacteria inside the
      Gunderboom as compared to the outside. In addition, significant differences (P <
      0.05) were found with lower numbers of E. coli and coliform bacteria recovered
      from the clams inside the Gunderboom compared to outside the Gunderboom. In
      conclusion, the Gunderboom system installed in Mamaroneck Harbor resulted in a
      significant reduction of E. coli and coliform bacteria in the water and clam
      samples, thus proving its efficiency as a water filter.

PMID- 17182385
TI  - Influence of cyclodextrin complexation on the Vibrio fischeri toxicity of
      phenylsulfonyl carboxylates.
AB  - This paper describes the research about the beta -cyclodextrin influence on
      Vibrio fischeri toxicity of 10 phenylsulfonyl carboxylates. It is illustrated
      that the formation of 1:1 cyclodextrin-solute inclusion complexes dominates the
      toxicity influence of phenylsulfonyl carboxylates to Vibrio fischeri and greatly
      weakens the toxicity level. Using the octanol-water partition coefficients lg
      KOW, the grouped electrotopological state (E-state) index S(> SO2) and the
      stability constants of inclusion complexes lg KS, three models with high squared
      correlation coefficients r2adj at 0.908, 0.951 and 0.917, respectively were
      constructed to evaluate the beta-cyclodextrin influence on Vibrio fischeri
      toxicity. For the type of phenylsulfonyl carboxylates, the inclusion stability
      constants lg KS can reliably model and predict the beta-cyclodextrin influence on
      Vibrio fischeri toxicity (TI).

PMID- 17182386
TI  - Sediment chronologies of As, Bi, and Ga in Sweden--impact of industrialisation.
AB  - The acid-leachable amount and pore water concentration of As, Bi and Ga in
      sediment cores from four remote lakes in a south to north transect in Sweden were
      used to recapitulate the pollution history of the elements. The diagenetic impact
      on the element distribution was elucidated from their solid/solution partition
      and relationships to elements indicative for diagenesis. Dating was made by their
      acid-leachable lead content in combination with the 206Pb/207Pb ratio. In one of
      the lakes this approach was validated against dating with 210Pb. The impact of
      diagenesis on the sediment distribution of theses elements was found to be low
      enough for a chronological interpretation of the sediment profiles, as evidenced
      by their ratios to elements indicative of the geological background. A closer
      examination of the diagenetic impact would however be required if a more detailed
      chronology is desired. This study has demonstrated that atmospheric deposition of
      arsenic, bismuth and gallium contributes to the sediment inventory of these
      elements. The major part of the deposition of arsenic and bismuth took place
      after the Second World War. For gallium no concentrations exceeding background
      were detected before circa 1930. Increased levels of arsenic are traceable to
      circa 1850. For bismuth increased levels are concluded to extend before 1790,
      i.e., background concentrations were not reached in the present cores. For all
      elements the atmospheric deposition has been lower towards the north.

PMID- 17182387
TI  - Treatment of wastewater containing Cu(II)-EDTA using immobilized TiO2/solar
      light.
AB  - The photocatalytic oxidation (PCO) of Cu(II)-ethylene diamine tetra-acetic acid
      (EDTA), employing immobilized TiO2, under natural sunlight rather than artificial
      UV light conditions, was investigated at a latitude 38 degrees. The immobilized
      TiO2 film was prepared using a sol gel process, the crystalline structure of
      which was identified, by X-ray diffraction analysis, as a mixture of the rutile
      and anatase forms. The PCO of Cu(II)-EDTA was examined in a circulating reactor
      with 20 L of 10(-4) M Cu(II)-EDTA and synthetic and real wastewaters at pH 4 and
      6.5, respectively. The removals of both Cu(II) and DOC were initially relatively
      rapid, but slowed as the reaction proceeded and generally followed first-order
      kinetics. The rate constants for the removal of Cu(II) and DOC were 1.1 x 10(-3)
      and 1.6 x 10(-3) min-1, respectively. The efficiency of the PCO in the
      decomplexation of Cu(II)-EDTA increased with increasing H2O2 dose using both the
      synthetic and real wastewaters. Therefore, we suggest the PCO process using the
      solar/immobilized TiO2 system, with addition of H2O2 as well as filtration for
      the removal of suspended solids, can be effectively applied to the treatment of
      Cu(II)-EDTA containing real wastewater.

PMID- 17182388
TI  - The foaming inhibitor on Nocardia and alike (FIONA) process.
AB  - A new process to abate foam-causing micro-organisms of the genus of Nocardia sp.
      and alike was developed in the Sha Tin Sewage Treatment Works of Hong Kong in
      2002 under an in-house research and development study. The new FIONA process
      relates to a process of inhibiting the growth of the foam-causing micro-organisms
      of genus Nocardia sp. and alike, which are commonly found in activated sludge
      sewage treatment process with nutrient removal. The Sha Tin Sewage Treatment
      Works is the largest secondary sewage treatment works in Hong Kong with nitrogen
      removal capability. It has been suffering from Nocardia foam since its
      commissioning in 1982, which had led to consistent non-compliant events. The new
      process has been put into full scale application since 2002 and its foaming
      abatement effect is very effective; resulting in resumption of full compliance
      with the discharge licence since November 2003. The FIONA Process basically
      comprises a chemical dosing system and a reaction zone with a mean hydraulic
      retention time of 1 hour. The dosing point of the Process can be at upstream
      sewage pumping stations as well as the inlet works of the sewage treatment works.
      The dosing chemicals are to create an anoxic environment in the sewage so as to
      boost up the removal of the readily biodegradable substrates, which are
      favourable substrates of the foam-causing micro-organisms, in the sewage prior to
      entering the bioreactors. In such way, it will help out-compete the foam-causing
      micro-organisms in the bioreactors. Full scale dosing results in the Sha Tin
      Sewage Treatment Works from 2002 to 2004 had demonstrated that the previous year
      round appearance of the Nocardia foam in the bioreactors had been greatly abated
      to an extent from little to moderate appearance only from January to April with
      complete Nocardia foam disappearance from May to December. The dosing chemical
      being used is calcium nitrate at dosing rates from 15 to 50 mL of aqueous calcium
      nitrate at 50% concentration by weight (equivalently 50 to 150 mM of calcium
      nitrate) per m3 of sewage. For other metallic nitrate salts, the nitrate mass
      content must be equivalent to the nitrate mass of calcium nitrate at the above
      dosing range. For hydrogen peroxide, it is believed the same effect would occur,
      however, there is no practical data available. A theory for the FIONA Process
      based on the bio-selector effect is also proposed albeit further research is
      necessary for its substantiation.

PMID- 17182389
TI  - Influence of nutrient level on biodegradation and bioconcentration of phthalate
      acid esters in Chlorella vulgaris.
AB  - Influences of major nutrients (N, P) on the biodegradation and bioconcentration
      of dibutyl phthalate (DBP) and di-2-ethylexyl phthalate (DEHP) by Chlorella
      vulgaris in lake water were investigated in this work. Our study demonstrated
      that nutrient addition obviously influenced biodegradation rate constants and
      apparent bioconcentration factors (BCFs) of DBP and DEHP in Chlorella vulgaris.
      The effects of P addition on biodegradation were less pronounced than the effects
      of N addition as a result of N-limitation status of phytoplankton in the lake
      water, while addition of both N and P more greatly affected biodegradation than
      addition of N or P. BCFs of DBP and DEHP decreased with increasing algal exudate
      as measured by dissolved organic carbon (DOC) and a strong correlation between
      BCFs and DOC was obtained. The results indicate that DOC plays an important role
      in the bioconcentration of DBP and DEHP.

PMID- 17182390
TI  - Removal of aluminium by constructed wetlands with water hyacinth (Eichhornia
      crassipes (Mart.) Solms) grown under different nutritional conditions.
AB  - This article reports the phytoremediation efficiencies of water hyacinth
      (Eichhornia crassipes (Mart.) Solms) grown under different nutritional conditions
      for Al rich wastewaters in batch type constructed wetlands (floating aquatic
      macrophyte-based plant treatment systems). This study was conducted for 15 weeks
      after 1 week acclimatization by culturing young water hyacinth (average height of
      20 +/- 2 cm) in 590 L capacity fiberglass tanks under different nutrient
      concentrations of 2-fold [56 and 15.4 mg/L of total nitrogen (TN) and total
      phosphorous (TP), respectively], 1-fold, 1/2-fold, 1/4-fold and 1/8-fold with
      synthetic wastewaters containing 5.62 Al mg/L. A control set-up of hyacinths
      comprising only Al with no nutrients was also studied. A mass balance was carried
      out to investigate the phytoremediation efficiencies and to identify the
      different Al removal mechanisms from the wastewaters. Chemical precipitation of
      Al(OH)3 was a dominant contribution to Al removal at the beginning of the study,
      whereas adsorption of Al3+ to sediments was observed to be a predominant Al
      removal mechanism as the study progressed. Phytoremediation mainly due to
      rhizofiltration was also an important mechanism of Al removal especially during
      the first 4 weeks of the study in almost all the set-ups. However, chemical
      precipitation and sediment adsorption of Al3+ was a dominant contribution to Al
      removal in comparison with phytoremediation. Plants cultured in the control set
      up showed the highest phytoremediation efficiency of 63% during the period of the
      4th week. A similar scenario was evident in the 1/8-fold set-up. Hence we
      conclude that water hyacinth grown under lower nutritional conditions are more
      ideal to commence a batch type constructed wetland treating Al rich wastewaters
      with a hydraulic retention time of approximately 4 weeks, after which a complete
      harvesting is recommended.

PMID- 17182391
TI  - Fluorochrome and flow cytometry to monitor microorganisms in treated hospital
      wastewater.
AB  - Flow cytometry with a fluorescent technique (FCM/FL), epifluorescence microscopy
      with a fluorescent technique (EFM/FL), and a culture method were used and
      compared to study the microorganism population profiles in wastewater treatment.
      In the two non-culture methods (FCM/FL and EFM/FL), four fluorescent dyes
      [acridine orange (AO), 4',6-diamino-2-phenylindole dihydrochloride (DAPI),
      propidium iodide (PI), and YOPRO-1] were used to determine the total
      concentration and viability of microorganisms in the wastewater samples. Results
      showed that the total cell concentrations (both the bacteria and fungi)
      determined by using the non-culture-based methods were 18 to 67 times higher than
      those by the culture method (p = 0.036): the total cell concentration ranged from
      1.10 x 10(7) to 2.44 x 10(8) cells/mL determined by both FCM and EFM with AO
      staining method, and from 1.02 x 10(7) to 2.00 x 10(8) cells/mL by EFM with DAPI
      staining method, whereas the culturable concentration of bacteria and fungi
      ranged from 0 to 3.22 x 10(6) CFU/mL and from 0 to 4.13 x 10(5) CFU/mL,
      respectively. No difference in total concentrations between dyes (AO and DAPI)
      and methods (FCM and EFM) were observed. By using EFM method, the microorganism
      viability ranged from 0.24 to 0.86 with PI staining and from 0.09 to 0.74 with
      YOPRO-1 staining. In the FCM analysis, the microorganism viability ranged from
      0.23 to 0.87 with PI staining and from 0.18 to 0.73 with YOPRO-1 staining. In
      addition, the cultivability of microorganism ranged from 0 to 0.105 by the
      culture method. The total concentrations and viabilities of microorganisms were
      highly underestimated by the culture method. Results also showed that the
      viabilities determined by using either EFM/FL or FCM/FL were significantly higher
      than the cultivabilities. In addition, significant difference in viability
      between PI and YOPRO-1 for both EFM and FCM analysis was observed. However, the
      difference in viability between EFM and FCM depended on dyes. In regard to the
      difference between bacteria and fungi, significant difference in total
      concentration, viability, and cultivability was observed. In conclusion, the
      EFM/FL and FCM/FL methods can effectively assess total concentration and
      viability of microorganisms in environmental samples.

PMID- 17182393
TI  - Simulating the transformation of heavy metals during coal or sewage sludge
      combustion.
AB  - A mathematical model (FPM) is presented to predict the transformation of heavy
      metals in the downstream of combustor or incinerator. The model accounts for the
      transformation of heavy metals through the combined effect of condensation,
      nucleation, coagulation, external force and thermophoresis force. The calculation
      of heavy metals is embodied in the post-processor appended to Fluent soft. Before
      the simulation, velocity, temperature, PbCl2 concentration and other initial
      parameters are obtained by experiment. In addition, the transformation of PbCl2
      is also experimentally studied. The comparison of experimental and predicted
      results indicate that the fine particle model (FPM) is valid for predicting the
      transformation of heavy metals in the downstream of incinerator or combustor.

PMID- 17182392
TI  - Removal of heavy metals from synthetic leachate using a biologically generated
      electric field.
AB  - Removal of heavy metals from aqueous solutions was investigated in batch reactors
      using a biologically generated electric field. An electric field with a potential
      difference of 50 mV to 100 mV was generated using an anaerobic culture and an
      aerobic culture couple. The electric field was applied to a synthetic leachate
      solution made up using cadmium, zinc or nickel salts using titanium-coated mesh
      electrodes. After 72 hours of exposure, at 15 mm electrode spacing, less than 40%
      removal of cadmium and zinc was observed while nearly 80% nickel removal
      occurred. After 72 hours and at an electrode spacing of 25 mm, nearly 40% removal
      of cadmium occurred, 60% of zinc was removed, and 80% of nickel was removed from
      solution. After 72 hours and at 45 mm electrode spacing, nearly 70% of cadmium,
      60% of zinc, and over 80% of nickel was removed. The tendency for zinc and
      cadmium to form more hydroxy complexes as compared to nickel may have contributed
      to these results. Cadmium and zinc removal were lower at an electrode spacing of
      15 mm and 25 mm, compared to removal at an electrode spacing of 45 mm. Electrode
      spacing did not affect nickel removal.

PMID- 17182394
TI  - A case study of Primary Progressive Aphasia: improvement on verbs after rTMS
      treatment.
AB  - This case-report shows that high frequency repetitive Transcranial Magnetic
      Stimulation (hf-rTMS), applied to the left prefrontal cortex, may improve the
      linguistic skills in Primary Progressive Aphasia (PPA). The patient's performance
      was evaluated on a battery of language production and memory span tasks, before
      and after two hf-rTMS treatments and one SHAM treatment. We observed a
      significant and lasting improvement of the patient's performance on verb
      production following the application of hf-rTMS versus Baseline and SHAM
      conditions. This finding suggests that hf-rTMS may directly strengthen the neural
      connections within an area of metabolic dysfunction and encourages the use of
      rTMS as an alternative therapeutic tool for neurodegenerative forms of aphasia.

PMID- 17182395
TI  - Functional imaging before and after constraint-induced language therapy for
      aphasia using magnetoencephalography.
AB  - Five patients with chronic aphasia underwent functional imaging using
      magnetoencephalography (MEG) before and after constraint-induced language therapy
      (CILT). Patients who responded well to CILT exhibited a greater degree of late
      MEG activation in posterior language areas of the left hemisphere and homotopic
      areas of the right hemisphere prior to therapy than those who did not respond
      well. Response to CILT, however, was positively correlated with the degree of pre
      therapy MEG activity within posterior areas of the right hemisphere only on an
      individual basis.

PMID- 17182396
TI  - Non-fluent progressive aphasia, depression, and OCD in a woman with progressive
      supranuclear palsy: neuroanatomical and neuropathological correlations.
AB  - This paper details the case of a 64-year-old woman who presented to the
      psychiatry service with worsening mood in the context of a diagnosis of obsessive
      compulsive disorder (OCD). On further examination she was found to have clinical
      findings consistent with frontotemporal lobar degeneration of the non-fluent
      progressive aphasia subtype. At post-mortem she was found to have progressive
      supranuclear palsy. We argue, in retrospect, that her OCD was likely prodromal to
      the development of her dementia. This case highlights the fact that
      frontotemporal lobar degeneration/progressive supranuclear palsy (FTLD/PSP) and
      other "tauopathies" represent a complex group of neurodegenerative disorders that
      may masquerade for many years as refractory psychiatric disorders.

PMID- 17182397
TI  - Neurocognitive sequelae of a giant arachnoid cyst: case study.
AB  - We conducted a comprehensive neuropsychological evaluation of a normally
      functioning man with a giant arachnoid cyst encompassing much of the space
      normally occupied by the left hemisphere. Although of solidly average
      intellectual ability, the patient demonstrated neurocognitive deficits only
      revealed upon neuropsychological assessment. Despite the remarkable left
      hemisphere lesion, the pattern of cognitive dysfunction suggested right
      hemisphere pathology. We review the arachnoid cyst literature and discuss the
      possibility of a crowding phenomenon by which language function relocates to the
      more viable hemisphere. This case illustrates striking preservation of higher
      cognition in the presence of substantial structural abnormality.

PMID- 17182398
TI  - Callosal neglect in hydrocephalus.
AB  - A functional disconnection of the corpus callosum (CC) can induce a form of
      spatial neglect where each hand (e.g., left) when attempting to bisect lines in
      the opposite (e.g., right) hemispace deviates toward its own (e.g., left)
      hemispace. Patients with hydrocephalus often show thinning of the CC but callosal
      neglect has not been reported in this condition. Two right-handed patients with
      hydrocephalus and thinning of the CC, as well as six matched controls, were
      assessed for neglect by performing the line bisection task in left, right and
      center space with their right and left hands. When compared to controls neither
      patient, using either their right or left hands, demonstrated a bias in the
      center or left space conditions, but with lines in right space both subjects'
      left hand deviated significantly to the left. Thus, patients with hydrocephalic
      interhemispheric functional disconnection might show a form of callosal neglect.
      This hemispatial-hand asymmetry of deviation, however, also might be related to
      the disinhibition of the attentionally dominant right hemisphere.

PMID- 17182399
TI  - Frontal executive impairment associated with paraneoplastic cerebellar
      degeneration: a case study.
AB  - Paraneoplastic cerebellar degeneration (PCD) is a rare cause of profound
      cerebellar dysfunction. Degenerative disorders of the cerebellum can cause
      cognitive and behavioral changes but the neuropsychological and behavioral
      sequelae of PCD are not well described. In this article, we detail selective
      frontal-executive disturbance, psychomotor slowing and affective change in a
      patient with PCD in whom there is no apparent extracerebellar involvement. The
      pattern of deficits suggests that PCD may be clinically dissociable from other
      forms of paraneoplastic encephalitis and correspond closely with the recently
      proposed "cerebellar-affective syndrome." The results underline the importance of
      the cerebellum in regulating cognitive function.

PMID- 17182403
TI  - Brow lift via the direct and trans-blepharoplasty approaches.
AB  - Brow ptosis occurs as part of the aging process, and as a complication of facial
      nerve paresis. The article addresses the options available for correction of brow
      ptosis. The direct brow lift is effective for medial and central brow ptosis, and
      additional lift laterally may occasionally be needed. This is achieved with
      either a temporal external lift or an internal lift combined with blepharoplasty.
      The direct brow lift is suitable for any degree and pattern of brow ptosis,
      usually in males. It is also suitable for older females as well as male patients
      with facial paresis or marked involutional brow ptosis. The trans-blepharoplasty
      brow lift is suitable for relatively small degrees of brow ptosis affecting
      mainly the lateral two-thirds of the brow in any age group. It is often combined
      with upper lid blepharoplasty and is performed through the same incision.
      Complications associated with the direct brow lift include a cosmetically
      disturbing scar, granuloma formation due to the use of braided absorbable sutures
      rather than monofilament sutures, and the brow descending again. There may be
      temporary patches of reduced sensation in the forehead which normally recover in
      a few months. Complications associated with the trans-blepharoplasty brow lift
      include less lift than desired, and sutures causing dimpling of the skin. These
      two techniques are useful additions to the approaches for patients with brow
      ptosis.

PMID- 17182402
TI  - Psychological elements contributing to cosmesis.

PMID- 17182400
TI  - From progressive nonfluent aphasia to corticobasal syndrome: a case report of
      corticobasal degeneration.
AB  - In a previous report, we presented longitudinal clinical, cognitive and
      anatomical data of a right-handed woman, whose clinical picture evolved from
      progressive nonfluent aphasia with apraxia of speech to corticobasal syndrome
      (CBS) in the last stage of the disease. The patient died at age 57 and
      pathological examination revealed severe atrophy in the left frontal operculum
      and left premotor area. On histological examination, there was diffuse tau
      positive pathology in gray and white cortical hemispheric gray and white matter,
      basal ganglia and substantia nigra, compatible with corticobasal degeneration
      (CBD). This case demonstrates the clinical overlap between frontotemporal lobar
      degeneration and CBD. In this case, early motor speech impairment predicted
      earlier and more accurately than CBS the presence of underlying tau-pathology and
      CBD.

PMID- 17182405
TI  - Complications of blepharoplasty.
AB  - The complications of blepharoplasty are infrequent, most often minor and
      transient, and rarely major and permanent with functional or aesthetic
      consequences. Treatment is above all preventive with screening of "at risk"
      patients in whom blepharoplasty would be contra-indicated. Patients must be
      informed of possible risks through informative booklets stressing the most
      important points. The complications may affect vision. Partial or complete visual
      loss due to ischemic optic neuropathy, or rarely to compression of the ocular
      globe by intraorbital hemorrhage, is the most serious complication. Other visual
      complications include oculomotor disorders, keratoconjunctivitis sicca, epiphora,
      and chemosis of lymphatic origin. Eyelid complications are more frequent: ptosis
      of the upper eyelid or lagophthalmia caused by incorrect resection of the skin,
      scarring, and eyelid fold anomalies. The most severe aesthetic complication is
      the malposition of the lower eyelid resulting in retraction, lagophthalmia,
      ectropion, deformation of the external canthus, or lower eyelid tissue
      relaxation. These malpositions are often minor, sometimes reversible, but they
      can be major, with psychological, aesthetic, and functional consequences. Other
      local complications include enophthalmia and hypo- or hypercorrection. General
      complications may include pigmentation anomalies or infections extending as far
      as the orbital fat tissue. Finally, complications observed after the newer
      procedures of laser surgery include ectropion, burns and residual redness.
      Complications related to periocular injections of filling material are also
      mentioned. The discussion of these complications is followed by a comprehensive
      review of the prevention, diagnosis and management of the complications after
      blepharoplasty.

PMID- 17182404
TI  - Endoscopic brow lifts uber alles.
AB  - Innumerable approaches to the ptotic brow and forehead have been described in the
      past. Over the last twenty-five years, we have used all these techniques in
      cosmetic and reconstructive patients. We have used the endoscopic brow lift
      technique since 1995. While no one technique is applicable to all patients, the
      endoscopic brow lift, with appropriate modifications for individual patients, can
      be used effectively for most patients with brow ptosis. We present the nuances of
      this technique and show several different fixation methods we have found useful.

PMID- 17182406
TI  - Combination therapies in oculofacial rejuvenation.
AB  - The oculo-facial surgeon's quest for non-invasive procedures is a response to
      increasing patient demands for enhanced results without any downtime. Technology
      has obliged us with multiple injectable and light therapeutic modalities that
      tighten skin, relax and fill in wrinkles, and improve skin dyspigmentation and
      texture. When these techniques are combined, the results are superior to the use
      of individual therapies alone. The foundation for combination therapies are:
      botulinum toxin, filling agents, chemical peels, intense pulsed light, non
      ablative and ablative lasers.

PMID- 17182407
TI  - Aesthetic surgery of the aging neck: options and techniques.
AB  - As the surgeon learns to address the aging changes of the forehead, brows,
      eyelids and cheeks, the natural progression is to understand aging of the lower
      one-third of the face and aging of the neck. An understanding of surface anatomy,
      a review of the underlying anatomical changes of aging and an overview of the
      palette of procedures applicable to the aging of the neck are presented to
      introduce the surgeon to this important part of the aging face.

PMID- 17182409
TI  - Abnormal multifocal electroretinogram (mfERG) in ethambutol toxicity.
AB  - OBJECTIVE: To report the abnormal multifocal electroretinogram (mfERG) findings
      in two cases of presumed ethambutol toxicity. DESIGN: Retrospective observational
      case series. PARTICIPANTS: Two patients with ethambutol toxicity and visual loss.
      TESTING: Multifocal electroretinography. MAIN OUTCOME MEASURE: Waveform
      measurements on multifocal electroretinography. RESULTS: Two patients with
      bilateral visual loss due to ethambutol toxicity underwent mfERG testing that
      disclosed both diffuse and central field loss compatible with retinal dysfunction
      as a contributing mechanism to the visual field loss. CONCLUSION: Ethambutol
      toxicity affects not only the optic nerve but probably other retinal elements
      based upon abnormal mfERG findings.

PMID- 17182410
TI  - GQ1b antibody testing in Guillain-Barre syndrome and variants.
AB  - Guillain-Barre syndrome (GBS) is characterized by an ascending muscle paralysis
      with progressive loss of muscle stretch reflexes. Annually, approximately 2.4
      cases per 100,000 population of GBS are reported. Variant forms do exist. These
      include the Fisher syndrome, GBS with ophthalmoplegia, Bickerstaff's brainstem
      encephalitis (BBE), and acute ophthalmoparesis without ataxia. In the last 15
      years, attention has been directed towards the association of the GQ1b IgG
      antibody and several GBS variants, particularly the Fisher syndrome and those
      associated with ophthalmoparesis. We present three cases of GBS variants. All
      three cases had associated ophthalmoplegia but only one of the three had a
      positive GQ1b antibody association.

PMID- 17182412
TI  - Traumatic unilateral internuclear ophthalmoplegia.
AB  - A 23-year-old man was admitted for a closed head injury following a fall from a
      height of 5 meters from a ladder. Because of a C-7 burst fracture, a halo and
      halo vest were applied approximately 9 hours following the fall. Approximately 21
      hours after the accident, the patient complained of diplopia. On neuro
      ophthalmology evaluation, a unilateral internuclear ophthalmoplegia was noted.
      MRI of the brain, performed 3 days after application of the halo and vest, showed
      a small infarct at the posterior aspect of the inferior midbrain, slightly left
      of midline. At 9.5 weeks there was 90% improvement of the internuclear
      ophthalmoplegia noted. Of the reported cases in the medical literature of
      traumatic internuclear ophthalmoplegia, 30 (83.33%) cases were male and 6
      (16.67%) were female. The mean age was 31.7. 54% of the cases were bilateral; 46%
      unilateral. Mechanisms include: motor vehicle accident: 28 (41.79%), fall: 7
      (10.45%), blunt trauma: 11 (16.42%), penetrating trauma 1: (1.49%), bike accident
      3: (4.48%), other: 1 (1.49%), Unknown: 16 (23.88%).

PMID- 17182411
TI  - "Staircase" saccadic intrusions plus transient yoking and neural integrator
      failure associated with cerebellar hypoplasia: a model simulation.
AB  - We present hypothesized ocular motor mechanisms of unique "staircase-like"
      sequences of saccadic intrusions in one direction that we have named, "staircase
      saccadic intrusions (SSI)," square-wave jerks/oscillations (SWJ/SWO), and
      transient failures of yoking and neural integrators in a patient with severe
      hypotonia, ataxic speech, motor and language developmental delays, and
      torticollis (Joubert syndrome). Brain magnetic resonance imaging showed
      hypoplasia of the cerebellar vermis and inferior cerebellar peduncles, abnormal
      superior cerebellar peduncles with deepening of the interpeduncular fossa, and
      enlargement of the fourth ventricle. During far and near fixation and smooth
      pursuit (rightward markedly better than leftward), the subject exhibited
      conjugate SSI (rightward more than leftward, with intersaccadic intervals
      equivalent to the normal 250 msec visual latency), SWJ, SWO, and uniocular,
      convergent and divergent saccades (including double saccades). Simulations using
      a behavioral ocular motor system model identified hypothetical mechanisms for
      SWJ, SWO, and SSI and ruled out the loss of efference copy as the cause. SSI may
      result from simultaneous dysfunctions: 1) a transient loss of accurate retinal
      error information and/or sampled, reconstructed error; plus 2) a constant
      sampled, reconstructed retinal error that drives saccades.

PMID- 17182414
TI  - Introduction to special issue on advances in the assessment and treatment of
      adolescent substance use disorders.

PMID- 17182413
TI  - Neuro-ophthalmologic manifestations of epilepsy.
AB  - This review summarizes the major neuro-ophthalmologic manifestations of epilepsy.
      Positive or negative visual manifestations such as hallucinations or visual loss
      may be seen. There is considerable overlap of the visual manifestations with
      migrainous aura and transient ischemic attack (TIA), making a detailed history
      important for accurate diagnosis. Oculomotor manifestations, such as tonic eye
      deviation, are often recognized to have localizing value. Nystagmus or repetitive
      blinking may be present and offer clues in clinically subtle seizures.

PMID- 17182415
TI  - Absence of iatrogenic or contagion effects in adolescent group therapy: findings
      from the Cannabis Youth Treatment (CYT) study.
AB  - Though widely used and presumed effective in practice, some scholars (Dishion et
      al., 1999) have raised the concern that group therapy for adolescents with
      substance use disorder and a range of deviancy has the potential for causing
      iatrogenic effects (e.g., increased substance use, behavior and legal problems)
      for those with low deviancy. Using data from 400 youth in the largest adolescent
      treatment experiment conducted to date (Dennis et al., 2004), this study shows
      that group composition in terms of conduct disorder symptoms is not associated
      with worse substance use, psychological, environmental or legal treatment
      outcomes. The results actually indicated that there was a slight advantage for
      youth with high conduct disorder to be included in the groups with less symptoms.
      The results appear consistent with recent meta-analyses of delinquency studies
      (Lipsey, 2006) which have found no evidence of iatrogenic effects. These results
      support the common clinical belief that group therapy for youths with substance
      use disorders is a safe and effective treatment modality.

PMID- 17182416
TI  - Adolescent and therapist perception of barriers to outpatient substance abuse
      treatment.
AB  - Attrition is one of the most vexing problems for the effective delivery of
      behavioral health services. Most prior studies focus on patient demographics and
      psychopathology factors predicting dropout. We examined patient and therapist
      post-treatment reports of barriers to attending treatment. Six hundred
      adolescents and their therapists completed the Perceived Barriers to Treatment
      scale (PBT) at discharge from a brief substance abuse intervention. After
      adjusting for covariates, results suggest that perceived barriers, in particular,
      practical obstacles, lack of treatment readiness, relevance, and compatibility,
      are related to sessions attended. Shifting to a more patient-centered approach
      for understanding treatment retention is discussed.

PMID- 17182417
TI  - Early therapeutic alliance as a predictor of treatment outcome for adolescent
      cannabis users in outpatient treatment.
AB  - The association of early alliance to treatment attendance and longitudinal
      outcomes were examined in 356 adolescents participating in a randomized clinical
      trial targeting cannabis use. Both patient and therapist views of alliance were
      examined, and outcomes were evaluated over 12 months after numerous other sources
      of variance were controlled. Patient-rated alliance predicted a reduction in
      cannabis use at three and six months and a reduction in substance-related problem
      behaviors at six months. Therapist-rated alliance did not predict outcomes.
      Neither patient nor therapist alliance ratings were associated with attendance.
      The findings support the important and often overlooked role that alliance can
      play in treating substance abusing, often delinquent, adolescents.

PMID- 17182418
TI  - Impact of victimization on substance abuse treatment outcomes for adolescents in
      outpatient and residential substance abuse treatment.
AB  - This paper considers whether victimization moderates adolescents' outcomes in
      substance abuse treatment. Adolescents (N=975) in outpatient and residential
      settings were assessed at intake, three, six, nine, and 12 months. Differential
      outcomes by gender and degree of victimization were analyzed. Dependent variables
      were marijuana use and substance-related problems. The residential sample
      reported higher baseline marijuana use and victimization. Both samples
      significantly reduced marijuana use and associated problems during treatment.
      Victimization was significantly related to more substance-related problems at
      intake and follow-up. More severe trauma histories in residential females were
      associated with significantly greater persistence in substance-related problems
      post-discharge.

PMID- 17182419
TI  - Suicidal ideation among adolescents with alcohol use disorders during treatment
      and aftercare.
AB  - The objectives of this study are to assess the magnitude and course of suicidal
      ideation during outpatient treatment and aftercare for adolescents with alcohol
      use disorders (AUD). One hundred seventy-seven adolescents meeting eligibility
      criteria, including no past 30-day suicidal behavior, participated in 9 weeks of
      outpatient cognitive-behavioral group therapy. Treatment completers were
      randomized into: (1) No-Active, (2) In-Person, or (3) Telephone aftercare
      conditions for a period of 12 weeks. No specific intervention for suicidal
      behavior was provided during the study. The Suicide Ideation Questionnaire (SIQ
      JR, Reynolds, 1988) was administered at baseline, end of treatment, and end of
      aftercare. The results are as follows, a higher baseline suicidal ideation was
      associated with higher retention at the end of treatment and through aftercare.
      The In-Person Aftercare condition showed a significant decrease in suicidal
      ideation, relative to the No-Active Aftercare condition. There was a trend for
      similarly reduced severity of suicidal ideation in the Telephone Aftercare
      condition. In conclusion, the type of aftercare and resulting decrease in AUD may
      play a role in the reduction in suicidal ideation. The mechanism of change by
      which suicidal ideation is reduced in adolescents in treatment for AUD needs to
      be further explored.

PMID- 17182420
TI  - Effects of motivational interviewing for incarcerated adolescents on driving
      under the influence after release.
AB  - Motivational Interviewing (MI) to reduce alcohol and marijuana-related driving
      events among incarcerated adolescents was evaluated. Adolescents were randomly
      assigned to receive MI or Relaxation Training. Follow-up assessment showed that,
      as compared to RT, adolescents who received MI had lower rates of drinking and
      driving, and being a passenger in a car with someone who had been drinking.
      Effects were moderated by levels of depression. At low levels of depression, MI
      evidenced lower rates of these behaviors; at high levels of depression, effects
      for MI and RT were equivalent. Similar patterns were found for marijuana-related
      risky driving, but effects were non-significant.

PMID- 17182421
TI  - Adolescent self-selection of service formats: implications for secondary
      interventions targeting alcohol use.
AB  - A novel motivational enhancement based secondary alcohol intervention has been
      shown to increase quit attempts for youth with heavier alcohol use histories
      (Brown et al., 2005). In the present study, we examined rates of self-selection
      into the three formats of this alcohol intervention: group, individual, and
      website; and examined differences between intervention participants and the
      general school population and across the three formats. Over four years, students
      at four schools were surveyed (n=6000) and were provided the opportunity to
      participate in Project Options (PO). Youth who were selected into PO (n=1147)
      were younger and more likely to identify as African American or Multiple/Other
      ethnicity than the school populations. More teens in PO reported lifetime alcohol
      use (65% vs. 60%); however, the school population reported more current (past 30
      day) drinking. Boys were more likely to utilize the group format and minority
      youth were more likely to select the individual format. Findings highlight the
      utility of multiple intervention formats to engage youth in early intervention
      for alcohol problems.

PMID- 17182422
TI  - Adolescents with co-occurring substance use and mental conditions in a private
      managed care health plan: prevalence, patient characteristics, and treatment
      initiation and engagement.
AB  - This study examined the prevalence, patient characteristics, and treatment
      initiation and engagement of adolescents with co-occurring substance use (SU) and
      serious mental health (MH) diagnoses in a private, managed care health plan. We
      identified 2,005 adolescents aged 12-17, who received both SU and MH diagnoses
      within a 1-year window between 1/1/2000 and 12/31/2002; 57% were girls. Gender
      variations were found in diagnoses received and point of identification. Being
      dually diagnosed in specialty departments (rather than Primary Care and
      Emergency) and receiving both diagnoses within a shorter time period were
      associated with treatment initiation and engagement.

PMID- 17182425
TI  - Changing provider practices, program environment, and improving outcomes by
      transporting multidimensional family therapy to an adolescent drug treatment
      setting.
AB  - Effective interventions for drug abusing adolescents are underutilized. Using an
      interrupted time series design, this study tested a multicomponent, multi-level
      technology transfer intervention developed to train clinical staff within an
      existing day treatment program to implement multidimensional family therapy
      (MDFT), an evidence-based adolescent substance abuse treatment. The sample
      included 10 program staff and 104 clients. MDFT was incorporated into the program
      and changes were noted in the program environment, therapist behavior, and in
      most (e.g., drug abstinence, and out of home placements) but not all (e.g., drug
      use frequency) client outcomes. These changes remained after MDFT supervision was
      withdrawn.

PMID- 17182424
TI  - The construct and predictive validity of different approaches to combining urine
      and self-reported drug use measures among older adolescents after substance abuse
      treatment.
AB  - Reconciling urine results and self-reports is a classic challenge in substance
      abuse treatment research in general. For adolescents, the problems are compounded
      by the facts that they are more likely to use marijuana (which takes longer to
      metabolize) and to be coerced into treatment (which may increase lying). This
      article examines the construct and predictive validity of several different
      approaches for combining urine and self reported drug use including using common
      individual measures (urine tests and self-reported recency, frequency, and peak
      use), taking either as positive, using a summary scale, and using a latent model.
      Data are from 819 older adolescents 24 to 42 months after intake in seven sites.
      Days of use, the GAIN's substance frequency scale, and a latent model were the
      three best methods in terms of construct and predictive validity. Implications
      for treatment and longitudinal evaluation will be discussed.

PMID- 17182426
TI  - Health care services use by adolescents with intakes into an outpatient alcohol
      and drug treatment program.
AB  - We examined utilization and cost in the 1 year pre- and post-intake among a
      sample of adolescents (N=419) entering chemical dependency (CD) treatment.
      Multivariate analyses showed that these youth used significantly more medical
      services than a demographically matched sample of members without substance use
      (SU) problems. Their utilization and costs were higher than matched members, and
      they did not show the same reductions in post-treatment costs that adults do.
      This is of concern since it would appear that the medical and mental health
      problems of adolescents entering CD treatment may be so severe that there are no
      short-term reductions in post-treatment cost, including ER and hospitalizations.

PMID- 17182423
TI  - Development and validation of the GAIN Short Screener (GSS) for internalizing,
      externalizing and substance use disorders and crime/violence problems among
      adolescents and adults.
AB  - The Global Appraisal of Individual Needs (GAIN)1 is a 1-2 hour standardized
      biopsychosocial that integrates clinical and research assessment for people
      presenting to substance abuse treatment. The GAIN - Short Screener (GSS) is 3-5
      minute screener to quickly identify those who would have a disorder based on the
      full 60-120 minute GAIN and triage the problem and kind of intervention they are
      likely to need along four dimensions (internalizing disorders, externalizing
      disorders, substance disorders, and crime/violence). Data were collected from
      6,177 adolescents and 1,805 adults as part of 77 studies in three dozen locations
      around the United States that used the GAIN. For both adolescents and adults the
      20-item total disorder screener (TDScr) and its four 5-item sub-screeners
      (internalizing disorders, externalizing disorders, substance disorders, and
      crime/violence) has good internal consistency (alpha of .96 on total screener),
      is highly correlated (r = .84 to .94) with the 123-item longer scales in the full
      GAIN. The GSS also does well in terms of its receiver operator characteristics
      (90% or more under the curve in all analyses) and has clinical decision-making
      cut points with excellent sensitivity (90% or more) for identifying people with a
      disorder and excellent specificity (92% or more) for correctly ruling out people
      who did not have a disorder. The GSS has good potential as an efficient screener
      for identifying people with co-occurring disorders across multiple systems and
      routing them to the right services and more detailed assessments.

PMID- 17182427
TI  - An interactive voice response (IVR) system for adolescents with alcohol use
      disorders: a pilot study.
AB  - In order to understand predictors of relapse among adolescents treated for
      alcohol use disorders (AUD), it is important to accurately assess the daily
      circumstances associated with use. This pilot study investigates the feasibility
      and acceptability of an interactive voice response (IVR) system in adolescents
      with AOSUD. Twenty-six adolescents 14 to 19 years old, with a mean age of 16.8,
      who were enrolled into an adolescent treatment program for AUD consented to make
      phone calls for 14 successive evenings to an IVR system and answer 14 questions
      pertaining to daily use of alcohol and other drugs. The subjects were compensated
      for their participation. A satisfaction questionnaire was administered at the end
      of the study. Participants completed 72% of scheduled recordings, with an average
      of 10.1 calls per subject. Most participants reported that they answered the
      questions honestly and accurately and were very much satisfied with the IVR
      system. The preliminary data presented here suggests that the use of IVR for the
      purpose of generating daily reports in youth is feasible and acceptable. The
      utilization of IVR systems should be explored to improve efficacy and attainment
      of generalizability to heterogeneous adolescent populations and lifestyles
      including for other psychiatric disorders.

PMID- 17182428
TI  - Cognitive behavioral treatment for suicidal alcohol abusing adolescents:
      development and pilot testing.
AB  - The purpose of this study was to pilot a cognitive behavioral treatment protocol
      for adolescents with co-occurring alcohol use disorder and suicidality, examine
      its association with symptomatic improvement, and determine its feasibility and
      acceptability. Treatment consisted of a 6 month acute treatment phase, 3 month
      maintenance phase, and a 3 month booster phase, as well as case management
      services. Participants were also permitted to receive concurrent pharmacotherapy.
      Five of six families completed the protocol. Measures of alcohol use and
      suicidality were collected at intake, end of acute treatment, and post-treatment.
      Decreases in alcohol use and suicidal ideation were reported for all
      participants. Two of the five participants, both with a prior history of suicide
      attempts, re-attempted during the course of the protocol. Both were maintained in
      the study and improved over the subsequent portion of the treatment. A high
      retention rate, strong therapeutic alliance ratings, and low perceived treatment
      obstacles provide support for the feasibility and acceptability of this
      intervention. Preliminary results suggest that integrated outpatient cognitive
      behavioral treatment for alcohol abusing suicidal adolescents is feasible,
      acceptable, and associated with symptomatic improvement.

PMID- 17182429
TI  - Comparative efficacy of family and group treatment for adolescent substance
      abuse.
AB  - Due to the continuing prevalence of adolescent substance abuse, promising
      treatment models need to be developed and evaluated. Thus, the purpose of this
      study was to evaluate the efficacy of two promising models, Strengths Oriented
      Family Therapy (SOFT) and The Seven Challenges(R) (7C). Adolescents who qualified
      for outpatient treatment and agreed to participate in our study were randomly
      assigned to one of the two treatments and assessed at 3 and 6-months following
      baseline. Using a two-part, random-effects model, we examined the odds of
      achieving abstinence or full symptom remission between treatments and over time.
      For those not achieving full abstinence or full problem remission, we
      investigated whether frequency of use or symptom severity were reduced at follow
      up. Participants in both SOFT and 7C demonstrated significant reductions in
      substance use and related problems, but treatments did not differ at 3 and 6
      months following baseline. Overall, treatment services were delivered as planned.
      Both SOFT and 7C were efficacious with adolescents who abuse substances, as
      participants in both conditions were significantly more likely to be in symptom
      remission or abstinent at follow-up interviews versus at baseline. Replication
      studies are needed that address this study's limitations.

PMID- 17182430
TI  - Employment and adolescent alcohol and drug treatment and recovery: an exploratory
      study.
AB  - Studies of adolescents in the general population show that most high school
      students are employed and that there is a positive linear relationship between
      hours worked and increases in alcohol and other drug use. Mixed methods are used
      to examine the relationship of employment for adolescents who are in outpatient
      substance abuse treatment to their use, treatment experiences, and recovery.
      Several theories offered to explain the relationship between adolescent
      employment and substance use were examined. Most adolescents were employed, often
      during treatment, with increasing numbers reporting employment over the year-long
      follow-up period. Adolescents reported frequent alcohol and other drug use after
      work and with coworkers and indicated that income from work often was used to
      purchase alcohol and other drugs. Most parents did not provide monitoring of work
      related income. Balancing employment and treatment was often logistically
      difficult and stressful for the adolescents. Employment situations are a critical
      aspect of adolescents' recovery environment, and more research is needed to learn
      how to create support for recovery in this aspect of an adolescent's life.

PMID- 17182431
TI  - Pediatric and adult hepatic embryonal sarcoma: a comparative ultrastructural
      study with morphologic correlations.
AB  - Hepatic embryonal (undifferentiated) sarcoma (ES) is a rare pediatric tumor
      occurring predominantly in the first decade of life, but a few examples of adult
      ES have also been described. Isolated ultrastructural reports describe
      contradictory lines of differentiation in these tumors. Four pediatric and 3
      adult ES cases were studied ultrastructurally and features were correlated with
      morphology. Morphologically, tumors were composed of mixture of plump spindle
      cells and bizarre giant cells, showing abundant cytoplasmic eosinophilic
      globules. Ultrastructurally, the hallmark features in all cases included dilated
      RERs and secondary lysosomes with dense precipitates. Dilated mitochondria and
      mitochondrial-RER complexes were often seen. Other features included
      intracytoplasmic fat droplets, scant actin microfilaments, and focal glycogen
      pools. In summary, pediatric and adult ES show similar morphologic and
      ultrastructural features. Ultrastructurally, hepatic ES have distinctive
      findings, including dilated RER and electron-dense lysosomal precipitates, which
      correlate with the eosinophilic hyaline bodies seen microscopically. These
      findings suggest that ES are composed of fibroblastic, fibrohistiocytic, and
      undifferentiated cells. Other lines of differentiation were not identified.

PMID- 17182432
TI  - Copper- and iron-rich matrices in hepatocellular lipofuscin particles of a young
      male patient: diagnostic ultrastructures for Wilson disease.
AB  - A 17-year-old male patient appeared with the biochemical liver damage associated
      with hypoceruloplasminemia and mild iron overload. Genetic analysis identified a
      compound heterozygosity of ATP7B responsible for the primary copper toxicosis of
      Wilson disease without mutations in HFE. A liver specimen consisted of cirrhotic
      nodules of large-sized hepatocytes with fatty change and those of fat-free small
      sized hepatocytes. Histochemically, iron was distributed diffusely in the small
      sized hepatocytes, while copper grains appeared in a few of the hepatocytes near
      the fibrous bands. X-ray microanalysis on the liver tissue fixed with a 0.1%
      osmium tetroxide solution and embedded in epoxy resin disclosed (1) complex
      formation of copper with sulfur, and iron with phosphorus in the hepatocyte
      lipofuscin particles, (2) intraparticle localization of the cuprothionein in the
      less dense matrix and ferric proteins in the dense matrix, and (3) high affinity
      of the cuprothionein to lead staining. Considering the fact that ceruloplasmin is
      the major ferroxidase essential for iron efflux, iron deposits in the
      hypoceruloplasminemic patients with Wilson disease are not a complication, but a
      natural event. This study disclosed for the first time the diagnostic
      ultrastructures of Wilson disease, which might represent different detoxification
      processes to the reactive metals of copper and iron.

PMID- 17182434
TI  - Ultrastructural investigation of Zimmermann-Laband syndrome.
AB  - Zimmermann-Laband syndrome (ZLS) is a very rare autosomal dominant inherited
      condition characterized by 3 major clinical findings of which gingival
      hyperplasia are always present. The great heterogenicity of the syndrome is
      illustrated by the numerous variable clinical findings described in the
      literature. The purpose of the study was to examine a patient diagnosed with ZLS
      and to describe possible new characteristics of this rare syndrome, including the
      ultrastructural morphology using a transmission electron microscope (TEM) of the
      gingival and dermal fibroblasts. The ultrastrucutral morphology as has not
      previously been described in the literature. Tissue was collected from the
      alveolar ridge and skin of the forearm for TEM. TEM studies indicated the
      presence of prominent fibroblasts situated among numerous regular dense
      connective tissue bundles. Genetic analysis showed a new chromosomal insertion,
      ins(12;8)(p11.2;q11.2q24.3), suggesting that the gene responsible for the
      syndrome lies on chromosome 8.

PMID- 17182433
TI  - Sickle cell anemia: conclusions from a forensic case report of a young African
      woman who died after anesthesia.
AB  - A 20-year old African woman underwent anesthesia for interruption of an unwanted
      pregnancy. As a consequence of the anesthesia, she went into coma because of an
      as yet unknown and untested homozygotic state of sickle cell anemia. Her vital
      functions were maintained for more than 1 year by intensive medicine, but she
      died finally in multiorgan failure and aspiration pneumonia. Because of the
      complications under anesthesia and the missing preanesthetic test for
      hemoglobinopathy, autopsy was conducted in the forensic medicine department and
      not in the department of pathology. The sickle cell disease was diagnosed by
      electrophoresis of the blood, by molecular detection of mutation in the
      hemoglobin gene, as well as by postmortem light and electron microscopy. Sickle
      cells were found in capillaries of brain, liver, lung, bone marrow, and spleen.
      Electrophoretic analysis revealed 80.2% HbS in addition to 3.2% HbA2 and 16.6%
      HbF, whereas no HbA0 could be detected in blood, confirming the homozygosity of
      sickle cell anemia. Because of sickle cell crisis, occluded blood vessels, and
      severe brain cortex necrosis, the patient died in spite of reanimation and
      intensive medicine. This case demonstrates that it is still important to realize
      the possibility of this disease and diagnostic obstacles even in regions where
      its manifestation is not endemic, as in Northern and Central Europe.

PMID- 17182435
TI  - The ultrastructural features of plasmablastic lymphoma.
AB  - Plasmablastic lymphoma was originally described in 1997 by Delecluse et al. and
      is an aggressive variant of diffuse large B-cell non-Hodgkin lymphoma seen
      predominantly in a setting of acquired immunodeficiency syndrome and nearly
      always in extranodal sites. The authors have seen 10 cases in their department
      between 2001 and 2005. The patients' ages ranged from 24 to 39 years and there
      were 7 females and 3 males. In 7 cases where human immunodeficiency virus had
      been tested it was positive. Eight cases were extranodal and 2 cases involved
      lymph nodes. Five cases were followed up and 4 were confirmed dead within 5
      months of diagnosis, verifying the aggressive nature of this condition. Histology
      showed large, polygonal tumor cells some of which had a slightly plasmacytic
      appearance. Six cases had a "starry sky" background. Immunohistochemical stains
      were negative in 1 case, while the other 9 cases were positive for CD138.
      Electron microscopy showed concentrically arranged rough endoplasmic reticulum in
      the cytoplasm in 9 cases. In 1 case the cells were too degenerate for evaluation.
      This study shows that the ultrastructural features are well developed and can
      help in distinguishing plasmablastic lymphoma from other light microscopically
      undifferentiated tumors.

PMID- 17182436
TI  - Ultrastructural changes in prostate cells during hormone-induced canine prostatic
      hyperplasia.
AB  - Benign prostatic hyperplasia is a prevalent disease that has received relatively
      little attention in spite of its morbidity and remarkable social impact. There
      are few animal models of prostatic hyperplasia. The dog is the only species,
      along with humans, in which prostatic hyperplasia develops spontaneously and
      almost universally with age. The aim of the present study has been to compare the
      ultrastructural findings in a model of experimentally induced canine prostatic
      hyperplasia with those of the spontaneously developed changes in untreated dogs.
      An experimental group of 5 male beagle dogs were castrated and treated with
      combined steroids (3 weekly doses for over 30 weeks). Prostate samples were
      surgically obtained every 42 days (experimental stages 0 through 6). The control
      group consisted of 3 noncastrated dogs that were treated with vehicle and in
      which samples were taken only at stages 0, 1, 4, and 6. Changes in the control
      groups were similar but of lower intensity compared to those of the experimental
      groups. In luminal cells, crowding with papillary projections, prominent,
      branching microvilli, and abundant, often compartmentalized granules were
      observed. The most striking change was the previously unreported finding of
      caveolae in basal cells. They were mostly located in the basal aspect of basal
      cells and were more prominent in the experimental group and in advanced stages of
      treatment. These ultrastructural findings have not been previously reported in
      canine or human prostatic hyperplasia and merit further research. The model of
      experimentally induced canine prostatic hyperplasia provides an adequate setting
      for the understanding of this disease.

PMID- 17182437
TI  - Comparative ultrastructural analysis and KIT/PDGFRA genotype in 125
      gastrointestinal stromal tumors.
AB  - GISTs are the most common mesenchymal neoplasms of the digestive tract and are
      thought to originate from or differentiate toward the interstitial cell of Cajal
      lineage. Almost all GISTs express KIT protein and the majority show activating
      mutations in either KIT or PDGFRA proto-oncogenes. Ultrastructurally, these
      tumors have been shown to have either a smooth muscle, neuronal, dual, or null
      phenotype. The objective of this study was to investigate the relationship
      between ultrastructural features and genotype in a large series of 125
      histologically confirmed and CD117 positive GISTs. PCR analysis for the presence
      of KIT exon 9, 11, 13, and 17 and PDGFRA exon 12 and 18 mutations was performed.
      There were 62 (50%) tumors located in the stomach and 45 (36%) in the small
      bowel. Overall, KIT mutations were detected in 93 (75%) patients: 86 (69%) in
      exon 11, and 7 (6%) in exon 9. A PDGFRA mutation was detected in 7 (6%) cases and
      25 (19%) cases had no mutation. Ultrastructurally, skeinoid fibers were seen in
      55 (44%) cases and were more common in small bowel than stomach GISTs, and
      occurred in only in 1 of 16 patients with an ITD (KIT) exon 11 or PDGFRA
      mutation. Focal actin microfilaments were identified in 82 (65%) cases and did
      not correlate with location or mutation type. Rare neurosecretory-type granules
      (NS-G) were seen in 34 (27%) of cases, but were seen in most of the cells in only
      5 (4%) cases. GISTs showing both NS-G and microtubules were associated with KIT
      exon 11 genotype and spindle cell morphology. PDGFRA mutated cases were
      associated with gastric location, predominantly epithelioid morphology and lacked
      NS-G.

PMID- 17182440
TI  - Plasticity of mesangial cells: a basis for understanding pathological
      alterations.
AB  - In the last two decades, the ability of mesangial cells to respond to various
      stimuli or injurious agents by altering their phenotype and function has become
      recognized. The plasticity of these mesangial cells has been linked to the
      morphological and functional alterations responsible for the pathologic findings.
      Many of the glomerular disorders target the mesangium as the primary and/or
      initial site of injury. Understanding how mesangial cells are altered in the
      various conditions provides a platform for conceptualizing pathologic mechanisms
      and defining key steps amenable to therapeutic intervention. The present paper
      reviews the normal and altered mesangium with an emphasis on mechanisms involved
      in alterations of mesangial homeostasis. Mesangial cells and matrix are very
      important in maintaining normal glomerular structure, and function and the
      plasticity of these cells is responsible for pathological manifestations, repair,
      and scarring. Our more sophisticated understanding of mesangial cell behavior and
      matrix biology provides very useful information to help design new therapeutic
      approaches to the treatment of renal diseases. The potential for bone marrow
      derived cells to differentiate into mesangial cells and repopulate damaged
      mesangium, thus "healing" what is today considered to be irreversible damage
      represents an exciting new area of research.

PMID- 17182439
TI  - Bupivacaine-induced regeneration of rat soleus muscle: ultrastructural and
      immunohistochemical aspects.
AB  - The regeneration of soleus muscle injury induced by the bupivacaine model was
      studied ultrastructurally and immunohistochemically. Twenty-one young (age range
      3-3.5 months) male Wistar rats were subjected to a single intramuscular injection
      of 1 mL of 0.5% Marcaine. The muscles were examined on biopsy days 1, 2, 3, 5, 7,
      14, and 21. By day 1, mononuclear inflammatory cells had invaded the necrotic
      sarcoplasm. Degenerative morphological findings counted mainly for the
      hypercontracted fibers, dilation of sarcoplasmic reticulum, plasma membrane
      defects, mitochondrial alterations, and myofibril discontinuities. By day 2
      proliferating myoblasts were seen with variety in shape, which fused on the day
      3. Myotubes with multiple central nuclei and euchromatic nucleoli were formed by
      day 5. Asynchronous repair events were seen with bundles of myofilaments toward
      the core of the fibers, in contrast to the least mature distal growth cones,
      which had free myoblasts in proximity and formatted pseudopods. Chronologically
      asynchronous regeneration stages possibly suggested successive satellite cell
      activation profiles or heterogeneity in satellite cell population. In parallel
      with the electron microscopy, in light microscope immunocytochemistry, desmin-
      and vimentin-positive mononuclear cells were observed within the first 3 biopsy
      days, but as regeneration proceeded, desmin predominated over vimentin. Merosin
      immunoreactivity revealed preservation of the basal lamina, which is crucial for
      the stability and survival of myotubes. By day 21, fibers restored the overall
      control architecture.

PMID- 17182441
TI  - Skin biopsy: a useful tool in the diagnosis of lysosomal storage diseases.
AB  - In this report, the authors summarize their 19-year experience with over 200
      biochemically proven cases of lysosomal storage diseases using electron
      microscopic screening of more than 950 skin biopsies. They found that electron
      microscopy (EM) is a highly sensitive, efficient, cost-effective, and rapid
      diagnostic screening tool for evaluation of lysosomal storage diseases in skin
      biopsies. Although EM is more expensive than a single enzyme assay, it can
      exclude more than 90% of cases in which lysosomal storage disease is being
      considered. EM is critical for diagnosis of neuronal ceroid lipofuscinosis and
      mucolipidosis IV and is the most cost-effective screening tool in patients with
      previously unrecognized storage diseases.

PMID- 17182438
TI  - Ultrastructural pathology of pediatric myocardium in acute ischemia: bioptic
      study before and after treatment with cardioplegic solution.
AB  - Protecting the myocardium from the risk of acute ischemia during heart surgery is
      still an unsolved problem; the problem is even more open and more pressing in
      pediatric heart surgery. To meet this greater risk it is advisable to use a
      cardioplegic solution with a composition that is better suited to the particular
      morphofunctional conditions of the myocardium in the child, i.e., a solution
      offering greater protection. To this purpose the authors experimented with
      Celsior cardioplegic solution during heart surgery in children to evaluate the
      efficacy compared to the standard St. Thomas solution. In this comparative study
      15 children were treated with Celsior cardioplegic solution and 15 others with
      St. Thomas cardioplegic solution. Each patient underwent 2 biopsies of the
      myocardium, the first before cardioplegic treatment and the second immediately
      after reperfusion. In both groups, focal lesions involving both the
      cardiomyocytes and the vascular-stromal structures were randomly found. The
      former had undergone a necrotic-regressive process with changes in the myofibrils
      and the mitochondria. The vascular-stromal structures showed changes in the
      permeability of the capillary endothelia, with interstitial edema. The results
      show the lesions to be similar in the 2 groups both on a quality and quantitative
      level.

PMID- 17182442
TI  - Validation of the revised Self-Administered Alcohol Screening Test (SAAST-R).
AB  - This study examined the sensitivity and specificity of the revised Self
      Administered Alcohol Screening Test (SAAST-R)1 among adult outpatients evaluated
      at community addictions and psychiatry and psychology clinics. A total of 417
      adults (mean +/- SD age of 41.4 +/- 15.0 years, 52% female, 91% Caucasian)
      completed the 36-item SAAST-R prior to their evaluation. Based on the clinician's
      documentation of the patient's alcohol use, two criterion groups were
      established: one composed of subjects classified as having no alcohol problems (n
      = 214), and one with alcohol problems (n = 203). The SAAST-R was found to have
      high internal consistency reliability (Cronbach's alpha = 0.96), sensitivity
      (90%), and specificity (82%) for differentiating outpatients with and without
      alcohol problems, respectively, using a cut point of >or=4 to indicate risk for
      alcohol-related problems. The SAAST-R was found to have good sensitivity and
      specificity among both males and females.

PMID- 17182443
TI  - Symptom severity, alcohol craving, and age of trauma onset in childhood and
      adolescent trauma survivors with comorbid alcohol dependence and posttraumatic
      stress disorder.
AB  - Posttraumatic stress disorder (PTSD) and alcohol dependence (AD) are frequently
      comorbid disorders. Given evidence that childhood traumas may be associated with
      broader, more severe psychological sequelae than later traumas, the present study
      examined whether the association between alcohol and trauma symptomatology is
      more pronounced among individuals with earlier trauma onsets in a sample of 42
      childhood and adolescent trauma survivors diagnosed with comorbid AD-PTSD. As
      predicted, individuals reporting childhood traumas reported greater severity of
      trauma and alcohol symptoms and greater alcohol craving. These results suggest
      that individuals with childhood trauma histories may be particularly vulnerable
      to relapse following AD treatment.

PMID- 17182444
TI  - Personality risk factors associated with trajectories of tobacco use.
AB  - The purpose of this longitudinal, prospective study was to evaluate trajectories
      of smoking in a cohort of African-American and Puerto Rican young adults and
      describe personality and behavioral factors associated with specific smoking
      trajectory group membership. Participants consisted of African-American and
      Puerto Rican male and female young adults (N = 451, mean age 26) from an inner
      city community. Data were collected at four time points over a period of 13 years
      using structured interviews. Interviews took place within the schools and the
      participants' homes. Scales with adequate psychometric properties were adapted
      from previously validated measures. Variables that were examined for this study
      came from the domains of internalizing behaviors, externalizing behaviors, drug
      use, and demographic information. Data were analyzed using latent growth mixture
      modeling to explore discrete smoking trajectories. Logistic regression analyses
      were then used to examine the risk factors associated with the various smoking
      trajectory groups. Four trajectory groups were determined to best fit the data:
      nonsmokers, maturing-out smokers, late-starting smokers, and early-starting
      continuous smokers. Subjects who were unconventional, experienced intrapersonal
      distress, and used alcohol and illegal drugs were more likely to belong to one of
      the smoking trajectory groups than to the nonsmoking group. The early-starting
      continuous group scored highest on these personal risk attributes. The long-term
      impact of unconventional behavior, intrapersonal distress, and drug use on
      developmental trajectories of smoking support the importance of early
      intervention and prevention.

PMID- 17182445
TI  - Outcome predictors in cocaine dependence treatment trials.
AB  - Finding the predictors of outcome in outpatient cocaine dependence treatment
      trials may be useful for the development of both psychosocial as well as
      pharmacological treatments for cocaine dependence. Among the most powerful
      predictors of response to psychosocial treatment are cocaine withdrawal symptom
      severity and the results of a urine drug screen (UDS) collected at study entry.
      The present trial seeks to extend these findings by examining outcome predictors
      in a large number of subjects participating in a series of outpatient cocaine
      pharmacotherapy trials while selecting three separate criteria to define
      successful outcome. The ability of several baseline variables were tested to
      predict treatment outcome in a series of cocaine medication trials that included
      402 cocaine-dependent subjects. Predictor variables included results from the
      baseline Addiction Severity Index (ASI), initial UDS results, and cocaine
      withdrawal symptom severity at treatment entry, as measured by scores on the
      Cocaine Selective Severity Assessment (CSSA). Outcome measures included UDS
      results obtained during the trials and results from the ASI gathered at the end
      of the trials. Baseline variables that most consistently predicted treatment
      outcome were the initial UDS results and initial CSSA scores. These findings
      indicate that baseline UDS results and CSSA scores are powerful predictors of
      outcome and should be used as stratifying variables in outpatient cocaine
      medication trials.

PMID- 17182446
TI  - What factors are associated with high-frequency drug treatment use among a
      racially and ethnically diverse population of injection drug users?
AB  - This study explored the frequency of drug treatment utilization by 36,081
      injection drug users (IDUs) in Massachusetts, 1996-2002. A number of multiple and
      logistic regression analyses examined the relationship between demographic
      characteristics, parental status, level of and type of drug use, history of
      mental health treatment use, types of drug treatment entered, and the number of
      times an IDU had entered drug treatment for the seven-year time period.
      Homelessness, using heroin as the primary drug of choice, and health insurance
      status were all associated with number of treatments entered. Logistic regression
      analysis identified that health insurance was a key factor associated with more
      frequent treatment: those with private health insurance were ten times more
      likely to be in the 90th percentile (12-107 entries) with respect to number of
      treatment entries.

PMID- 17182447
TI  - Maternal cigarette smoking during pregnancy and child aggressive behavior.
AB  - This study's objective was to examine the association between maternal smoking
      during pregnancy and childhood aggressive behavior in African-American and Puerto
      Rican children, as well as the relationship between maternal unconventional
      behavior, low maternal affection, and offspring aggression. Participants
      consisted of African-American and Puerto Rican children (N = 203; mean age = 8.6,
      SD = 0.87) and their mothers living in an inner city community. An interview
      consisting of a structured questionnaire was administered to the mothers and
      their children. Scales with adequate psychometric properties were adapted from
      previous validated measures. They included maternal smoking during pregnancy,
      maternal education, unconventionality, and warmth. Controlling for demographic
      factors, maternal unconventional behavior, and low maternal warmth, maternal
      smoking during pregnancy was associated with having offspring who were
      aggressive. Maternal unconventionality and warmth were independently related to
      childhood aggression. Although causal limitations are noted, it may be that a
      decrease in smoking during pregnancy is associated with a reduction in aggression
      in the offspring.

PMID- 17182450
TI  - Association between opium abuse and comorbidity in diabetic men.
AB  - The aims of this study were to determine the prevalence of opium abuse in
      diabetic men and to investigate its association with comorbidity. The study
      population was comprised of 312 consecutive diabetic men aged 20 years or older
      residing in the study area in 2005. The prevalence of self-reported opium abuse
      was 11.2%. Opium use was associated with low socioeconomic status, smoking, tea
      consumption, and a higher prevalence of erectile dysfunction (ED) and severe
      depression. The prevalence of severe depression was 22.8% among 35 men who used
      opium and 13.4% among 277 who did not use it. The prevalence of moderate or
      severe ED was 85.7% among opium users and 66.1% among non-users. The risk of ED
      was two times (95% CI 1.0-7.4) higher in opium users compared with nonusers.

PMID- 17182448
TI  - More severe violence exposure associated with poly-pharmaceutical use.
AB  - Exposure to emotional, physical, and sexual abuse carries varying psychological
      and somatic sequelae, including the increased use of alcohol and illicit drugs.
      Less studied is the association between violence exposure and prescription drug
      use. Using previously determined lifetime exposure profiles of 16,000 men and
      women, the current use of three specific drug categories was assessed and a
      strong relationship between victimization severity and prescription drugs used
      within the last month was found. Victimization screening has important
      implications in health care settings.

PMID- 17182449
TI  - Abstinence and initiation of treatment following inpatient detoxification.
AB  - This prospective cohort study compared in-patients who remained abstinent and
      initiated aftercare treatment following detoxification with those who did not. Of
      110 patients enrolled, 58% (46/79) were totally abstinent and 72% (67/93)
      initiated treatment during the first 30 days following hospital discharge.
      Patients who relapsed after hospital discharge were more likely than those who
      remained abstinent to have a primary drug-use disorder (p = 0.05), prior mental
      health treatment (p = .007), or previous incarceration (p = 0.035). Those who
      initiated aftercare treatment were less likely to have had prior mental health
      treatment than those who did not (p = .046).

PMID- 17182451
TI  - Cocaine use and syphilis trends: findings from the arrestee drug abuse monitoring
      (ADAM) program and syphilis epidemiology in Houston.
AB  - There has been speculation that trends in syphilis have been fueled by crack
      cocaine use. This study examined the data on syphilis notifications and arrestee
      drug abuse monitoring (ADAM) to ascertain the relationships between syphilis and
      cocaine use trends in three racial/ethnic groups. Syphilis notifications and data
      from the ADAM project were compared in Houston/Harris County, Texas, from 1991
      1998 using a linear regression equation. Data indicated significant relationships
      between the data for cocaine use and syphilis in African Americans but not
      Hispanics or non-Hispanic whites. For African Americans, 58% of the variance
      between cocaine use and syphilis was explained. When data limited to jail
      syphilis notifications and ADAM cocaine in African Americans were examined, the
      association was stronger for males than for females. For African Americans,
      cocaine (probably crack cocaine) use trends were significantly associated with
      syphilis trends in this population. These data suggest that control of crack
      cocaine may have an impact on syphilis rates and that there may be close
      relationships between some STDs and drug abuse.

PMID- 17182452
TI  - Demographic characteristics and antisocial personality disorder of early and late
      onset alcoholics identified in a primary care clinic.
AB  - A total of 1,734 persons were prospectively screened in a primary care clinic to
      examine the demographic characteristics and presence or absence of antisocial
      personality disorder among early onset alcoholics (EOA) and late onset alcoholics
      (LOA). A total of 76 EOA (male = 58 and female = 18) and 80 LOA (male = 56 and
      female = 24), as determined by the Comprehensive Drinking Profile Scale,
      participated in the study. EOA tended to be single and were younger, in a lower
      socioeconomic class, raised by non-biological parents, more likely to have
      antisocial personality disorder, and more likely to commit certain convicted
      offenses compared to LOA (p <or= .05). This study found that EOA identified in a
      primary care clinic have a different demographic profile and are more likely to
      have antisocial personality disorder compared to LOA.

PMID- 17182453
TI  - Permanent neurologic damage from chronic gamma hydroxybutyrate abuse.

PMID- 17182454
TI  - Cannabis withdrawal among adolescent cannabis users in an outpatient research
      setting.

PMID- 17182459
TI  - Encouraging responsible drinking among underage drinkers.
AB  - Public Service Announcements tailored to specific college drinking rituals
      (Treise, Wolburg and Otnes 1999) were tested on 133 underage undergraduate
      drinkers. More significant reductions in drinking intentions were found when
      using appeals focusing on drinking rituals pertaining to Maturity/Order (older
      students drink moderately: "Don't drink like a freshman.") than to Transformation
      (desired personality and mood changes), Community (social bonding and
      camaraderie), or a no-message Control. Gender did not moderate this effect.
      Underage drinkers may drink, in part, to feel more "grown up." Emphasizing that
      more senior students actually drink responsibly may diminish this belief and
      result in reduced alcohol consumption among underage students.

PMID- 17182460
TI  - Enhancing marketing recruitment strategies: administrator tenure and nursing
      expenditures.
AB  - When recruiting nurses, long-term care facilities require an ability to identify
      salient organizational characteristics that are attractive to potential nursing
      services candidates vis-a-vis their competitors. The findings of this study
      suggest that information on administrative tenure can be utilized to attract
      applicants by appealing to criteria within their high-involvement job search
      activities. High-involvement applicants proactively seek recruitment content that
      provides essential job attributes that match their needs and skills and are more
      apt to be a higher quality candidate. Based upon the study's findings, managers
      are offered marketing strategy recommendations for tailoring recruiting messages
      that appeal to high-involvement job seekers.

PMID- 17182462
TI  - The impact of unacceptable wait time on health care patients' attitudes and
      actions.
AB  - A great deal of time is spent by patients waiting for health care services in
      doctors' offices. The literature points to a negative impact of wait time on
      patients' perceptions of health care services, and on patients' subsequent
      behavior. A survey of 200 patients suggests wait time affects perceptions of
      quality, satisfaction and likeability, as well as likelihood of recommendations
      and repeat visits. In addition, response to unacceptable wait time was found to
      be significantly related to income. These findings indicate a cultural shift in
      patients' perceptions of wait time, and underline the need for providers to
      retain patients' loyalty through more timely service.

PMID- 17182461
TI  - Promoting alcohol abstinence among pregnant women: potential social change
      strategies.
AB  - Fetal Alcohol Syndrome Disorder (FASD) is one of the most preventable sources of
      developmental abnormalities, and has a singular cause-alcohol consumption during
      pregnancy. Estimates for the costs of treatment of a single case of FASD range
      often above one million dollars. The primary strategy for prevention currently
      centers on no alcohol consumption during pregnancy. However, a sizeable number of
      North American women currently drink during pregnancy. A literature review
      examined the behavior of maternal alcohol consumption in order to understand the
      rationale associated with drinking. Generally, it appears that pregnant women
      differ by their alcohol consumption habits and their reasons to drink. In an
      attempt to eliminate FASD, we review a number of educational, legal, and
      community-based programs that have been used to promote abstinence and examine
      where they have been successful. Unfortunately, social marketing strategies have
      received less attention. Several potential applications of social marketing
      directed to drinking-during- pregnancy campaigns are suggested, and possible
      contributions to the overall effort are explained.

PMID- 17182463
TI  - Great time to be involved in older adult nutrition.

PMID- 17182464
TI  - Undernutrition risk screening and length of stay of hospitalized elderly.
AB  - The purpose was to compare, in elderly hospitalized patients, the performance of
      widely used nutritional screening and assessment tools and anthropometric
      parameters with the Nutritional Risk Screening (NRS-2002); and to evaluate their
      independent association with length of hospital stay. Nutritional-status
      screening and assessment was carried out using NRS-2002, Mini Nutritional
      Assessment (MNA), Subjective Global Assessment (SGA), Malnutrition Screening Tool
      (MST), and anthropometry. Patients classified by NRS-2002 as undernourished had
      an independent higher risk of longer length-of-stay (> 8 days): Odds ratio = 2.25
      (95% Confidence Interval = 1.03 to 4.88). Nutritional "risk" by NRS-2002 is an
      independent risk factor for a long length of stay in elderly hospitalized
      patients, an important outcome predictor in this population.

PMID- 17182465
TI  - Nutritional status of the tribal elderly in India.
AB  - The objective of the paper is to assess the diet and nutritional status of the
      tribal elderly (> or = 60 years) using data from a cross-sectional study carried
      out by National Nutrition Monitoring Bureau (NNMB) exclusively in Integrated
      Tribal Development Project (ITDP) villages of 9 provincial States in India during
      1998-1999. A total of 1,239 elderly completed the diet survey (24-hour recall)
      and 3,932 elderly completed anthropometric measurements. In general, the mean
      consumption of all the foods and the median intakes of all the nutrients were
      below the Recommended Dietary Intakes (RDI) in both men and women. The mean
      heights and weights significantly decreased with increase in age in both males
      and females (p < 0.001). The prevalence of Chronic Energy Deficiency (CED = BMI <
      18.5) was relatively higher (65.4%) in females compared with their male
      counterparts (61.8%). The prevalence of CED was significantly higher (p < 0.001)
      among the elderly living in kutchaand landless households. The tribal elderly are
      subsisting on inadequate diets, which are reflected in the poor intakes of all
      the nutrients and higher prevalence of undernutrition. Significantly higher
      proportion of tribal elderly are undernourished compared with their rural
      counterparts (p < 0.001).

PMID- 17182466
TI  - The effects of nutrition-related factors on four-year mortality among a biracial
      sample of community-dwelling elders in the North Carolina piedmont.
AB  - The purpose of this epidemiological study was to estimate mortality risk
      associated with poor diet quality (consumption of five food groups), extremes of
      body mass index (BMI), waist circumference, and impaired food-related activities
      of daily living among community-dwelling older Black and White men and women. The
      design of the current study was a retrospective-prospective cohort study. The
      sample included residents (n = 1920) of five North Carolina Piedmont counties.
      The dependent variable was four-year all-cause mortality. Analyses were
      stratified by gender and race, and controlled covariates included: age, living
      with others, income, smoking and alcohol use, cognitive status, and overall self
      rated health. Data were self-reported to interviewers, except BMI and waist,
      which were measured by trained interviewers. Difficulty in fixing meals elevated
      the risk of mortality between 2.7 and 6.5 times across the four gender-race
      groups. Among older adults, inability to fix a meal conferred more risk of
      mortality than did lack of financial means. Adequate servings of vegetables were
      uniformly protective, although significant only among Black males. Neither BMI
      nor waist circumference conferred significant mortality risk. These population
      based findings suggest relationships between nutrition risk factors and mortality
      that are unique and require further focused studies.

PMID- 17182467
TI  - Factors associated with Oklahoma Older Americans Act Nutrition Program
      participants ability to shop, cook, and feed themselves.
AB  - Oklahoma Older Americans Act Nutrition Program participants' (n = 859) ability to
      shop, cook, and feed themselves was evaluated using factor analysis and logistic
      regression. Congregate participants who reported they were not able to shop,
      cook, and feed themselves had significantly lower "mobility," "financial
      management," and "financial security" factor scores; home-delivered participants
      had significantly lower "mobility," "living arrangement" and "financial
      security," and higher "social interaction" factor scores. For congregate meal
      participants the factors "mobility" and "financial management" and for home
      delivered meal participants, the factors "mobility" and "social interaction" were
      significantly associated with reported ability to shop, cook, and feed
      themselves.

PMID- 17182468
TI  - Participant characteristics predicting voluntary early withdrawal from a
      multidisciplinary program providing home-delivered meals and dietitian/social
      work case management to homebound elders.
AB  - We examine whether baseline characteristics of participants enrolled in a
      multidisciplinary program providing home-delivered meals and dietitian/social
      work case management to homebound seniors predicted voluntary early withdrawal.
      Sixty-nine participants voluntarily withdrew early and 111 completed the project.
      Six hypotheses were based on a conceptual framework incorporating (1) agreement
      between project elements and needs/preferences of individuals and (2) whether
      participants would improve and no longer require or desire the intervention.
      Three of the hypotheses were supported by means of logistic regression analysis.
      Voluntary early withdrawers at baseline: (1) were more mobile, (2) ate less
      often, and (3) responded that food tastes good less often. The results suggest
      that carefully considering the interaction of potential participant
      characteristics and project interventions will improve nutrition project
      retention.

PMID- 17182469
TI  - Assessing healthful eating among community dwelling rural older adults using self
      reported fruit and vegetable consumption via a community-wide mail-out health
      status assessment.
AB  - This project assessed fruit and vegetable intakes among rural older adults on a
      regional mail-out community health assessment. Over 95% of respondents answered
      questions regarding fruit and vegetable consumption. Rural older adults in this
      sample were willing to respond to questions regarding their fruit and vegetable
      intake; yet they were not likely to be meeting minimum recommended intakes of
      these foods. Including questions about dietary healthfulness on such an
      assessment may provide key stakeholders and policymakers a clearer understanding
      of their community's overall health status.

PMID- 17182474
TI  - Perceptions of cancer fatalism and cancer knowledge: a comparison of older and
      younger African American women.
AB  - Cancer fatalism (the belief that death is inevitable when cancer is present) may
      influence cancer screening practices among older African American women. Little
      is known about cancer fatalism among younger women. Guided by the
      Patient/Provider/System Model, this descriptive study compares cancer fatalism
      and cancer knowledge among African American college students (n = 353) and women
      from primary care centers (n = 361). Their average age was 29 years. Data were
      collected using the Powe Fatalism Inventory and breast and cervical cancer
      knowledge scales. Women at health centers had higher cancer fatalism and lower
      cancer knowledge. Differences in life experiences may help explain these
      findings.

PMID- 17182475
TI  - Turning curses into blessings: an Eastern approach to psychosocial oncology.
AB  - Cancer patients experience enormous psychological stress in addition to their
      physical suffering. Neither disease- nor symptomspecific approaches in the
      conventional Western medical model or single- modal psychological intervention
      focusing on stress and anxiety are sufficient to relieve patients of their pain
      and trauma resulting from cancer. Through years of working with Chinese cancer
      patients and witnessing their growth and resilience, we were motivated to develop
      an Eastern Body-Mind-Spirit (BMS) Group Intervention model which has a strong
      emphasis on turning crisis into opportunities, and growth through pain. This
      model blends different intervention approaches, techniques, and outcome measures
      both from the East and the West. This paper describes our intervention approaches
      and discusses the theoretical background in relation to the concept of
      transformation and some qualitative findings which provide evidence for the
      study's applicability and effectiveness.

PMID- 17182476
TI  - Social perception of speech in individuals with oropharyngeal reconstruction.
AB  - Oral cancer affects approximately 5% of the Canadian population every year. One
      option for treatment of oropharyngeal cancer includes resection of the diseased
      tissue with primary reconstruction of the defect using a microvascular free flap,
      followed by post-operative adjuvant radiation therapy. The aim of reconstructive
      surgery is to maintain functional speech and swallowing. While the literature
      provides support for the maintenance of speech intelligibility following
      reconstructive procedures, certain aspects of resonance may be altered when the
      palatal structures are involved. Little is known about the effect of such
      alterations on the perception of speakers who have been treated with
      microvascular free flap reconstruction. Social perception is a process in which
      we infer attributes of others, with the speech signal playing an integral part in
      attribution. The purpose of this study was to explore the social perceptions
      formed about speakers both before and after surgery for oropharyngeal cancer. The
      results of this study revealed that positive perceptions of speakers
      significantly diminished as a result of surgery and negative perceptions
      increased. Certain variables, such as degree of resection of the soft palate and
      base of tongue, and sex of the speaker, had influence on the results. This
      research suggests that intelligibility measurements of speech, although useful,
      do not provide a complete indication of the social impact of reconstructive
      surgery on patients with oropharyngeal resections.

PMID- 17182477
TI  - Survivorship: a qualitative investigation of Latinas diagnosed with cervical
      cancer.
AB  - Latinas experience high rates of cervical cancer (CCA) in the U.S. This health
      related quality of life (HRQOL) qualitative study was conducted with key
      informant and focus groups (N = 26). The results indicate that overall Latinas
      experience persistent concerns: Physical challenges including pain, and bladder,
      bowel, and sexual health problems; medical care barriers (e.g., difficulties
      accessing quality care, poor patient-physician relationship); functional issues
      including employment difficulties; and personal concerns including family and
      relationship burdens. Spiritual, familial, and cultural factors promote coping
      and well-being but may delay care seeking. In summary, Latinas diagnosed with CCA
      face a burdensome survivorship experience. Increases in medical and psychosocial
      services are greatly needed for Latinas to improve cancer outcomes including
      HRQOL.

PMID- 17182479
TI  - Breast cancer survivorship: expressed needs of black women.
AB  - Studies have reported that race/ethnicity, socioeconomic status, access to care,
      early diagnosis, quality of care, and spirituality are important prognostic
      factors for a breast cancer diagnosis. This exploratory study seeks to identify
      the perceived needs of Black middle-income breast cancer survivors. The Delphi
      Technique, a qualitative research approach (for deriving cultural consensus), was
      used to assess needs of 62 Black middle-income socioeconomic position survivors.
      Survivors' expressed needs were to have (1) affordable, accessible, acceptable,
      and appropriate medical and support services; (2) a caring and loving family; (3)
      contacts for information regarding breast cancer symptoms or related health
      problems; (4) an intimate relationship with God; and (5) adequate resources for
      self and family care. This pilot study suggests Black breast cancer survivors,
      regardless of a middle-income socioeconomic position (SEP), experience similar
      socioecological stressors as low-income SEP survivors.

PMID- 17182478
TI  - Measurement in group interventions for women with breast cancer.
AB  - Instrumentation is a critical component of intervention research. This article
      discusses a review of measurement tools used in research on group interventions
      for women with breast cancer. The wide variety of instruments used in research
      studies is listed. The criteria for instrument selection are compared with the
      most commonly used instrument, the Profile of Mood States. The authors summarize
      directions for future research related to instrumentation use.

PMID- 17182480
TI  - Coping in adolescents with cancer: a review of the literature.
AB  - The dual challenge of normal adolescent development combined with a diagnosis
      places high demands on the coping of adolescents with cancer (AWC). A review was
      conducted to synthesize and critique studies of coping in AWC. Findings from this
      review indicated inconsistent results for developmental and gender differences as
      well as associations of coping with distress. A number of limitations were
      associated with these studies, including the use of small samples, lack of
      consistency in the conceptualization of coping and instruments, and limited
      knowledge helpful to inform intervention research to improve effective coping in
      AWC. Future studies are needed to address these limitations.

PMID- 17182482
TI  - The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible
      neuroprotective and cognitive enhancing agent.
AB  - L-theanine (N-ethyl-L-glutamine) or theanine is a major amino acid uniquely found
      in green tea. L-theanine has been historically reported as a relaxing agent,
      prompting scientific research on its pharmacology. Animal neurochemistry studies
      suggest that L-theanine increases brain serotonin, dopamine, GABA levels and has
      micromolar affinities for AMPA, Kainate and NMDA receptors. In addition has been
      shown to exert neuroprotective effects in animal models possibly through its
      antagonistic effects on group 1 metabotrophic glutamate receptors. Behavioural
      studies in animals suggest improvement in learning and memory. Overall, L
      theanine displays a neuropharmacology suggestive of a possible neuroprotective
      and cognitive enhancing agent and warrants further investigation in animals and
      humans.

PMID- 17182481
TI  - Analysis of ephedra-free labeled dietary supplements sold in the San Francisco
      Bay area in 2003.
AB  - OBJECTIVE: To sample dietary supplements (DS) labeled as ephedra-free to evaluate
      whether products met their labeling claim. METHODS: One control DS product
      containing ephedra alkaloids and 29 DS labeled as ephedra-free were purchased
      from various retail locations in San Francisco. All products were sent to the
      California Department of Health Services (CDHS), Food and Drug Laboratory for
      content and quantity analysis. All laboratory personnel were blinded to product
      names and labeled contents. All DS products were screened for the presence of
      undeclared drugs, ephedra alkaloids, and heavy metals including lead, arsenic,
      cadmium and mercury. All products were also evaluated for compliance with the
      labeling requirements of the Dietary Supplement Health and Education Act (DSHEA)
      of 1994. RESULTS: None of the DS labeled as ephedra-free tested positive for the
      presence of ephedra alkaloids; as expected, the control product did test
      positive. Heavy metals were detected in three ephedra-free labeled DS products.
      All 24 products that tested positive for caffeine listed caffeine or a botanical
      source of caffeine on the DS label. All but two products were in compliance with
      DS labeling as required by DSHEA. CONCLUSIONS: This study demonstrates that
      manufacturers met their labeling claims for ephedra-free products. Special
      attention should be given to the presence of heavy metals and other drugs like
      caffeine, synephrine, and botanical sources of caffeine as these ingredients have
      replaced ephedra.

PMID- 17182483
TI  - The use of medicinal herbs by diabetic Jordanian patients.
AB  - Diabetes mellitus is the most common metabolic disorder worldwide. To date, there
      have been no reports on the frequency of use of herb medicines in the managements
      of diabetes mellitus in Jordan. This cross-sectional study was conducted by
      interviewing 310 diabetic patients visiting two medical centers in Jordan: Jordan
      University of Science & Technology Medical Center and Sarih Medical Center
      between December 2003 and August 2004. It is found that 31% of interviewed
      patients have used herbal products (96 patients). The results revealed that the
      most commonly used herbs by diabetic patients in Jordan were Trigonella
      foenumgraecum (22.9%), Lupinus albus (14.6%), Allium sativum (11.5%), Allium cepa
      (5.2%), Nigella sativa (7.3%), Zea mays L. (6.3%), Urtica dioica L. (8.3%),
      Eucalyptus globules LA (9.4%), Olea europea L. (3.1%), Cumminum cyminum (9.4%),
      Coriandrum sativum (10.4%), Salvia officinalis L. (3.1%), and Tilia cordata (1%).
      Furthermore, it is found that 47.9% of the patients used herbs according to
      advice from their friends on a daily basis. The side effects were reported by
      36.5% of the patients and include headache, nausea, dizziness, itching,
      palpitation, and sweating. Among the patients, 72.9% used the herbs as adjunctive
      therapy along with their anti-diabetic drugs and 80.2% of the patients informed
      their physicians about their use. A 79.2% of the sample confirmed their intention
      to re-use these herbs as 86.5% of them were satisfied with their diabetes
      control. There was a significant relationship between the use of herbs, the
      patient's place of residence and his/her level of education. The main conclusion
      of this survey is that the use of medicinal herbs among diabetic patient in
      Jordan is common. Therefore, it is essential to increase the level of awareness
      among diabetic patients and health care providers regarding the efficacy and
      toxicity of these medicinal herbs.

PMID- 17182484
TI  - Anti-ulcer activity of Adhatoda vasica Nees.
AB  - Adhatoda vasica Nees (Acantheceae), commonly known as Vasaka, is a well-known
      plant in indigenous systems of medicine and is used for its beneficial effects,
      particularly in bronchitis. The present investigation was carried out to study
      the anti-ulcer activity of Adhatoda vasica leaves using two ulcer models (1)
      Ethanol-induced, and (2) Pylorus ligation plus aspirin-induced models. Adhatoda
      vasica leaf powder showeda considerable degree of anti-ulcer activity in
      experimental rats when compared with a control. The highest degree of activity
      (80%) was observed in the ethanol-induced ulceration model. Results of the study
      suggest that in addition to its classically established pharmacological
      activities, the plant also has immense potential as an anti-ulcer agent of great
      therapeutic relevance.

PMID- 17182485
TI  - Herb use among health care professionals enrolled in an online curriculum on
      herbs and dietary supplements.
AB  - BACKGROUND: Although many adults in the United States use herbs, little is known
      about the personal use of herbs by health care professionals (HCPs) and factors
      associated with use. METHODS: We performed a cross-sectional study of HCPs prior
      to their enrollment in an online course about herbs and dietary supplements
      between September 2004 and May 2005. We used multivariable logistic regression to
      analyze demographic and practice factors associated with herb use. RESULTS: Of
      the 1249 health care professionals surveyed, 51% reported using an herb in the
      last week. The rates of use were highest among physician assistants or nurse
      practitioners (PA or NP) (63%), clinical nurses (59%), and HCP students (52%),
      while physicians (48%), dietitians (40%), and pharmacists (37%) had lower rates.
      Among health care professionals who reported herb use, the most common herbs
      taken were green tea (24%), flax seed (18%), chamomile (11%), and aloe vera (8%).
      Factors associated with herb use included older age, being a nurse, a HCP
      student, an NP or PA compared with being a physician, being non-Caucasian, living
      outside of North Carolina and having increased knowledge of herbs and dietary
      supplements.

PMID- 17182486
TI  - Inhibitory effects of peony root extract on the large conductance calcium
      activated potassium current essential in production of bursting activity.
AB  - To elucidate the mechanism of inhibitory action of peony root extract on
      pentylenetetrazol-induced bursting activity, effects of peony root extract on the
      iberiotoxin-sensitive large conductance calcium-activated potassium (BKCa)
      current that plays an essential role in the production of bursting activity were
      investigated. Peony root extract showed a clear inhibitory effect on the
      iberiotoxin-sensitive calcium-activated potassium current. Peony root extract
      also showed clear inhibitory effects on spontaneous bursting activity and BKCa
      current in the cerebral cortical neurons of the EL mouse, a hereditary epilepsy
      animal model. These results together with our previous studies, including the
      protective effect against neuron damage, indicate that peony root extract is a
      promising herbal drug for inhibition of convulsions.

PMID- 17182488
TI  - Colon cleansing: a popular, but misunderstood natural therapy.
AB  - Intestinal inflammation and leaky gut syndrome can be at the root of many health
      problems. Colon cleansing is a popular therapy among alternative practitioners,
      but many myths surround it. The scientifically inaccurate way many traditional
      healers try to explain therapeutic mechanisms is one of the obstacles that
      inhibits dialog between traditional healers and practitioners of modern medicine.
      The therapy actually has clinical value, but the explanations used to promote the
      therapies are the stuff of herbal legends, not scientific fact. The concept of
      cleansing is actually a metaphorical explanation for a therapy that improves
      detoxification via the liver and gastrointestinal tract and reduces inflammation
      or irritation to mucous membranes of the GI tract.

PMID- 17182489
TI  - Agave (Agave americana): an evidence-based systematic review by the natural
      standard research collaboration.
AB  - An evidence-based systematic review including written and statistical analysis of
      scientific literature, expert opinion, folkloric precedent, history,
      pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and
      dosing.

PMID- 17182487
TI  - Punica granatum (pomegranate) extract is active against dental plaque.
AB  - In the present work, we studied the effect of the hydroalcoholic extract (HAE)
      from Punica granatum (pomegranate) fruits on dental plaque microorganisms. The
      study was conducted on 60 healthy patients (33 females and 27 males, with age
      ranging from 9 to 25 years) using fixed orthodontic appliances, and randomly
      distributed into 3 groups of 20 patients each. The first group (control) used
      distilled water, while the second and third groups used chlorhexidine (standard)
      and HAE as mouth-rinses, respectively. The dental plaque material was collected
      from each patient, before and after a 1-min mouth-rinse with 15 ml of either
      distilled water, chlorhexidine or HAE. In both dental plaque collections, the
      material was removed from patients without oral hygiene, for 24 h (no tooth
      brushing). Dental plaque samples were diluted in phosphate buffered saline (PBS)
      plated on Mueller-Hinton agar, and incubated for 48 h, at 37 degrees C. Results,
      expressed as the number of colony forming units per milliliter (CFU/mL), show
      that the HAE was very effective against dental plaque microorganisms, decreasing
      the CFU/ml by 84% (CFU x 10(5)), before mouth-rinse: 154.0 +/- 41.18; after
      mouthrinse: 25.4 +/- 7.76). While similar values were observed with
      chlorhexidine, used as standard and positive control (79% inhibition), only an
      11% inhibition of CFU/ml was demonstrated in the distilled water group, negative
      control (CFU x 10(5)), before mouth-rinse: chlorhexidine, 208.7 +/- 58.81 and
      distilled water, 81.1 +/- 10.12; after mouth-rinse: chlorhexidine, 44.0 +/- 15.85
      and distilled water, 71.9 +/- 8.68). The HAE presented also an antibacterial
      activity against selected microorganisms, and may be a possible alternative for
      the treatment of dental plaque bacteria.

PMID- 17182490
TI  - Introduction: exploring dissociation: setting the course.

PMID- 17182491
TI  - Different types of "dissociation" have different psychological mechanisms.
AB  - The term "dissociation" has been used to describe a wide range of psychological
      and psychiatric phenomena. The popular conception of dissociation describes it as
      a unitary phenomenon, with only quantitative differences in severity between the
      various dissociative conditions. More recently, it has been argued that the
      available evidence is more consistent with a model that identifies at least two
      distinct categories of dissociative phenomena-"detachment" and
      "compartmentalization"- that have different definitions, mechanisms and treatment
      implications (Holmes, Brown, Mansell, Fearon, Hunter, Frasquilho & Oakley 2005).
      This paper presents evidence for this bipartite model of dissociation, followed
      by definitions and descriptions of detachment and compartmentalization. Possible
      psychological mechanisms underlying these phenomena are then discussed, with
      particular emphasis on the nature of compartmentalization in conversion disorder,
      hypnosis, dissociative amnesia and dissociative identity disorder.

PMID- 17182492
TI  - The dissociative processing style:a cognitive organization activated by perceived
      or actual threat in clinical dissociators.
AB  - This paper proposes a cognitive organization that operates during times of
      perceived or actual threat in individuals with dissociative psychopathology. This
      organization, referred to as the dissociative processing style (DPS), serves as a
      threat monitoring system. It is characterized by (1) a shift from selective
      attention processing to multiple streams of information processing, (2) weakened
      cognitive inhibitory functioning which allows these streams to be operational and
      (3) the directing of awareness towards some and away from other information
      streams. Whilst DPS activation has the potential for adaptive and protective
      functions, it also heightens the likelihood of dissociative symptom experience
      and dissociation itself. Dissociation is understood as a failure to integrate
      encoded information from multiple input streams. The DPS is argued to be
      activated by top-down processes which signal danger, such as the appraisal of
      contextual cues. A clinical example is used to highlight the characteristics of
      the DPS.

PMID- 17182493
TI  - A model of dissociation based on attachment theory and research.
AB  - The article offers an historical review of studies on the role played by
      attachment processes in dissociative psychopathology. The treatise proceeds from
      Bowlby's first insights, through Main and her collaborators' empirical studies on
      attachment disorganization, to the first formulation of the hypothesis linking
      disorganized early attachment to pathological dissociation. Recent research
      supporting the hypothesis is then reviewed. It is concluded that infant
      attachment disorganization is in itself a dissociative process, and predisposes
      the individual to respond with pathological dissociation to later traumas and
      life stressors. Four implications of this theory are interspersed in the review
      and are discussed in the final section: (1) pathological dissociation should be
      viewed as a primarily intersubjective reality hindering the integrative processes
      of consciousness, rather than as an intrapsychic defense against mental pain; (2)
      early defenses against attachment-related dissociation are based on interpersonal
      controlling strategies that inhibit the attachment system; (3) dissociative
      symptoms emerge as a consequence of the collapse of these defensive strategies in
      the face of events that powerfully activate the attachment system; (4)
      psychotherapy of pathological dissociation should be a phase-oriented process
      focused primarily on achieving attachment security, and only secondarily on
      trauma work. Research studies on the psychotherapy process could test some
      predictions of this model.

PMID- 17182494
TI  - Development of dissociation: examining the relationship between parenting,
      maternal trauma and child dissociation.
AB  - While many studies have demonstrated relationships between trauma and
      dissociation, relatively little is known about other factors that may increase
      children's risk for developing dissociative symptoms. Drawing on betrayal trauma
      theory and Discrete Behavioral States frameworks, the current study examined the
      contributions of maternal factors (including mothers' dissociation, betrayal
      trauma experiences, and inconsistent parenting) to children's dissociation.
      Seventy-two mother-child dyads completed self-report questionnaires. Maternal
      dissociation was found to relate positively to maternal betrayal trauma history.
      Additionally, both mothers' and children's betrayal trauma history were found to
      significantly predict children's dissociation. Implications for the
      intergenerational transmission of betrayal trauma and dissociation are discussed.

PMID- 17182495
TI  - Investigating peri-traumatic dissociation using hypnosis during a traumatic film.
AB  - We investigated the hypothesis that inducing a dissociative response (detachment)
      in healthy volunteers while they were watching a trauma film would lead to
      increased numbers of intrusive memories of the film during the following week.
      Hypnotized participants were given suggestions to dissociate during part of the
      film, and to watch the rest of the film normally from their own perspective. The
      order of these conditions, and the section of film watched under the two
      conditions, were counterbalanced. As predicted, watching the film under both
      conditions led to increases in dissociation. Explicit suggestions to dissociate
      were generally effective in inducing higher levels of dissociation. Contrary to
      prediction, there were no more intrusive memories of sections of the film for
      which participants had received dissociation suggestions. Implications of our
      results for views of the relationship between peri-traumatic dissociation and
      intrusive memories are discussed.

PMID- 17182496
TI  - Dissociation: cognitive capacity or dysfunction?
AB  - Dissociative experiences are mostly studied as a risk factor for dissociative
      pathology. Nonpathological dissociation is quite common in the general
      population, however, and may reflect a constitutionally determined cognitive
      style rather than a pathological trait acquired through the experience of adverse
      life events. In a theoretical model, we propose that nonpathological dissociation
      is characterized by high levels of elaboration learning and reconstructive
      retrieval, for which enhanced levels of attentional and working memory abilities
      are a prerequisite. These characteristics, in general, seem to be representative
      for a higher ability to (re-)construct conscious experiences. We review some of
      our behavioral as well as neural (i.e., fMRI, ERPs) studies, suggesting that high
      dissociative individuals are characterized by heightened levels of attention,
      working memory and episodic memory. In nonpathological conditions a person may
      benefit from these dissociative abilities, although after adverse (e.g.,
      traumatic) events the disposition may develop into dissociative pathology.

PMID- 17182497
TI  - The relationship between executive attention and dissociation in children.
AB  - Dissociation involves disruption in the usually integrated functions of
      consciousness, memory, identity, and perception. Recent research with adults
      suggests that dissociation is associated with alterations in attention. Little
      work, however, has examined the attentional correlates of dissociation in
      childhood. This study is the first to investigate the specificity of cognitive
      functions related to dissociation in children. Twenty-four 5- to 8-year-old
      foster children completed several subtests of the NEPSY: A Developmental
      Neuropsychological Assessment (Korkman, Kirk, & Kemp, 1998) in the Executive
      Functioning/ Attention domain. Foster caregivers completed the Child Dissociative
      Checklist (Bernstein & Putnam, 1986). Consistent with the adult literature,
      higher levels of childhood dissociation were associated with deficits in tasks
      requiring inhibition, but not with tasks requiring primarily planning, strategy,
      or multiple rule sets.

PMID- 17182501
TI  - Coxibs and NSAIDs: a chronology of confusion.

PMID- 17182504
TI  - High dose controlled-release oxycodone in hospice care.
AB  - Controlled-release oxycodone (OxyContin) is commonly used for pain relief in
      terminal cancer. This opioid may be considered as a treatment option for patients
      who prefer oral pain control, but who are unwilling to take oral morphine
      sulphate or cannot tolerate its side effects. However, little is documented about
      the use of high doses of this drug in terminal cancer patients. The purpose of
      this study was to investigate the clinical characteristics of terminally ill
      hospice inpatients treated with OxyContin for pain, and to compare those patients
      receiving high-dose OxyContin (150 mg/day) with patients taking low and more
      typical doses. This retrospective chart analysis with parallel groups included
      records of 97 consecutive terminal cancer patients. We recorded clinical and
      demographic data, as well as data regarding daily doses, rescue doses and
      parameters associated with quality of life. The mean daily OxyContin dose was
      78.6 mg per day for all patients. Only 18 (18.55%) patients were treated with
      high doses (mean daily dose 231.1 mg). No statistically significant correlations
      were found between any of the deomographic parameters and dose ranges, with the
      exception of patients with painful bony metastases who consumed significantly
      higher doses (p = 0.008). No differences were observed in sleep quality or mood
      as a factor of OxyContin doses. However, compared with patients receiving low
      dose (OR 1.0), patients treated with moderate and high doses maintained Karnofsky
      scores higher than 40 points most of the time (OR = 3.77, CI 1.1-13.0 and OR
      4.95, CI 0.8-29.9, respectively). Survival was not related to OxyContin doses
      (Log Rank test, p = 0.12; Breslow test, p = 0.37). We conclude that the use of
      high dose OxyContin for terminal cancer pain management is safe, efficient, and
      unrelated to shorter survival times. The results suggest that health care
      professionals may use higher OxyContin doses, when indicated, to enable better
      pain relief and quality end-of-life care.

PMID- 17182503
TI  - Celecoxib versus a non-selective NSAID plus proton-pump inhibitor: what are the
      considerations?.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used worldwide.
      However, associated adverse gastrointestinal effects (NSAID gastropathy) such as
      bleeding, perforation and obstruction result in considerable morbidity,
      mortality, and expense. Although it is essential to employ gastroprotective
      strategies to minimize these complications in patients at risk, controversy
      remains on whether celecoxib alone or a non-selective NSAID in conjunction with a
      proton-pump inhibitor (PPI) is a superior choice. Recent concerns regarding
      potential cardiovascular toxicities associated with cox-2 selective inhibitors
      may favor non-selective NSAID/PPI co-therapy as the preferred choice. Concomitant
      use of low-dose aspirin with any NSAID increases the risk of gastrointestinal
      complications and diminishes the improved gastrointestinal safety profile of
      celecoxib; whereas use of ibuprofen plus PPI regimens may negate aspirin's
      antiplatelet benefits. Evidence shows that concurrent use of a non-selective
      NSAID (such as naproxen) plus a PPI is as effective in preventing NSAID
      gastropathy as celecoxib, and may be more cost-effective. Patients failing or
      intolerant to this therapy would be candidates for celecoxib at the lowest
      effective dose for the shortest duration of time. Potential benefits from using
      low-dose celecoxib with a PPI in patients previously experiencing bleeding ulcers
      while taking NSAIDs remains to be proven. An evidence-based debate is presented
      to assist clinicians with the difficult decision-making process of preventing
      NSAID gastropathy while minimizing other complications.

PMID- 17182507
TI  - Overdose risk prompts UK withdrawal of propoxyphene combination.
AB  - The January 31, 2005 withdrawal of the propoxyphene-paracetamol (acetaminophen)
      from clinical use in the United Kingdom is described.

PMID- 17182505
TI  - Zoster vaccine to prevent postherpetic neuralgia.
AB  - In 2006, the U.S. Food and Drug Administration approved the first vaccine for the
      prevention of acute herpes zoster neuralgia (shingles). This vaccine has
      important implications in reducing the incidence and severity of the common
      neuropathic pain condition postherpetic neuralgia. The new vaccine is described.

PMID- 17182508
TI  - Drug combinations in pain management.
AB  - Combinations of two or more drugs in analgesic regimens are described. Clinical
      implications of such combinations are discussed.

PMID- 17182509
TI  - Treating pain in the older person.
AB  - Clinical guidance on the management of pain in elderly patients is presented. The
      way in which pain presents in elderly people and how it differs form other
      segments of the population are discussed.

PMID- 17182510
TI  - Back pain intensity underestimated.
AB  - A quality assurance program conducted by German physicians and physiotherapists
      about back pain is described. The results of the program documented that this
      common disorder was underestimated in over half of the cases.

PMID- 17182511
TI  - Your questions answered.

PMID- 17182513
TI  - The American Medical Association "Pain Management: the Online Series".
AB  - There is a growing number of Internet based programs on pain management. Many of
      them offer continuing medical education credits (CMEs). "Pain Management: The
      Online Series" from the American Medical Association (AMA) is a recent addition.
      Its content is robust but the self-assessments tests needed to obtain CME are
      weak.

PMID- 17182514
TI  - Equianalgesic dosing of opioids.
AB  - The concept of opioid equianalgesia, limitations in current dose conversion
      systems, equianalgesic dose tables, and computer assisted dose conversions are
      discussed. Conversions for methadone, fentanyl and hydromorphone are described.

PMID- 17182515
TI  - Restless legs syndrome: an update on diagnosis and management.
AB  - Restless legs syndrome (RLS) is a relatively common disorder that leads to
      considerable distress in and of itself and amplifies other physical symptoms,
      such as pain, by exacerbating sleep disturbance in affected patients. Due to its
      prevalence, it is important to query patients about this syndrome, evaluate for
      treatable causes, and provide palliative therapy to optimize comfort and
      normalize sleep patterns. This brief review summarizes current understanding of
      pathophysiology, epidemiology, differential diagnosis, and treatment modalities.

PMID- 17182516
TI  - Huntington's Chorea, Leukemia at end-of-life, G-tubes, open access to hospice.
AB  - This feature is based on actual questions and answers received and responded to
      by the Hospice Foundation of America (HFA). This is a service provided for
      families and support group members of patients with advanced disease by William
      M. Lamers, MD, HFA Medical Consultant a member of this Journal's Editorial Board.
      Effective ways to communicate with families and support groups of patients with
      advanced disease are presented. In this issue, queries and responses are
      presented addressing Hubtington's Chorea, Leukemia at end-of-life, the use of G
      tubes, and open access to hospice care.

PMID- 17182517
TI  - The role of the pain psychologist, trigger point injections, reflex sympathetic
      dystrophy.
AB  - This feature presents information for patients in a question and answer format.
      It is written to simulate actual questions that many pain patients ask and to
      provide answers in a context and language that most pain patients will
      comprehend. Issues addressed in this issue are the role of the pain psychologist,
      trigger point injections, and reflex sympathetic dystrophy.

PMID- 17182519
TI  - Evidence-Based Pain Management and Palliative Care in Issue Two for 2006 of The
      Cochrane Library.
AB  - The Cochrane Library of Systematic Reviews is published quarterly. It now
      contains 2674 complete reviews, 1686 protocols for reviews in production and 6019
      one page summaries of systematic reviews published in the general medical
      literature. In addition there are citations of 473,442 randomized controlled
      trials, 22 methodology reviews and 8255 cited papers in the Cochrane methodology
      register. The health technology assessment database contains 5648 citations. This
      edition of the Library contains 66 new reviews of which 4 have potential
      relevance for practitioners in pain and palliative medicine.

PMID- 17182520
TI  - Drowning or thirsting: the extremes of availability of medical information.
AB  - The March 2006 issue of PLoS Medicine contains the following editorial and a
      thoughtful debate on the issue of direct-to-consumer advertising of prescription
      drugs. The same issue contains a fascinating article on a "low tech" approach to
      information management, the blue trunk approach. This electronic journal is one
      of several published by the non-profit Public Library of Science (PLoS), a non
      profit organization of scientists and physicians committed to making the world's
      scientific and medical literature a freely available public resource. PLoS
      Medicine is an open-access, on-line journal that contains timely discussions and
      new findings on a broad range of medically-related topics. Readers are referred
      to the PLoS Medicine website: http://www/plosmedicne.org to read the full pro and
      con debate mentioned in this paper and to learn more about this valuable
      intellectual resource.

PMID- 17182524
TI  - The association between disordered eating and substance use and abuse in women: a
      community-based investigation.
AB  - A behavioral analysis was conducted of various eating disorder behaviors and
      their relationship with the lifetime use of different substances in a community
      based sample of young adult women, aged 18-25 years. Women with particular eating
      disorder behaviors were selected from the 517 women who completed the Women's
      Health Survey. Analyses compared the frequencies of lifetime use of a range of
      licit and illicit substances as well as the abuse of prescription medications
      between each of the eating disorder groups and the normal control group. Results
      showed that as eating disorder behaviors became more severe, or were clustered
      together, the number of substance classes used, increased. Severe bingeing was
      consistently associated with alcohol use. Dieting and purging, with or without
      bingeing, was associated with the use of stimulants/ amphetamines and the abuse
      of sleeping pills. The results of this study suggest that the co-occurrence
      between subclinical levels of eating disorders and the use and abuse of a wide
      range of substances should inform assessment and treatment planning for adult
      women.

PMID- 17182525
TI  - Diaphragm acceptability among young women at risk for HIV.
AB  - OBJECTIVES: The purpose of this study was to increase understanding of
      acceptability of the diaphragm among young women at risk for HIV and other
      sexually transmitted infections (STIs) in the U.S. METHODS: A total of 140 young
      (aged 18-25 years) women who had never used the diaphragm and who were at risk
      for HIV and other STIs completed questionnaires that included questions about the
      diaphragm and other sexual and reproductive health topics. These women were
      participants in a focus group study. RESULTS: The majority of participants
      perceived that the diaphragm had several characteristics (e.g., is a method they
      can control, is effective in preventing pregnancy, will not cause side effects,
      does not decrease sexual pleasure) considered important when selecting a birth
      control method. However, most were not confident in various aspects of diaphragm
      use, including their ability to use the method correctly, without breaking the
      mood, or when sexually excited. In multivariate analyses, intention to use the
      diaphragm was significantly higher among participants who were less motivated to
      avoid pregnancy and those with greater perceived self-efficacy to use a diaphragm
      in different contexts (e.g., when sexually excited). CONCLUSION: The diaphragm
      has characteristics that some women consider desirable, suggesting that it could
      be an acceptable HIV prevention method for some at-risk women.

PMID- 17182526
TI  - Barriers to physical activity among women in the rural midwest.
AB  - Physical activity is an important factor in chronic disease control and
      prevention. Yet women and rural residents consistently report lower rates of
      physical activity than their male and urban/suburban counterparts. The objective
      of this study was to assess the relationship between personal, social, and
      environmental barriers and meeting moderate physical activity recommendations in
      a sample of rural women. Data were obtained from a telephone survey of 2,510
      residents of rural southeastern Missouri, Tennessee, and Arkansas. After
      adjusting for age and income, women who identified personal barriers, such as
      lack of time, no motivation, disinterest in exercise, and having no one to
      exercise with were less likely to meet physical activity recommendations. There
      was evidence of a dose-response relationship between the number of barriers
      identified and meeting moderate physical activity recommendations among women
      with higher incomes and women with lower incomes; however, this relationship was
      most striking among women with annual household incomes of 25,000 US Dollar or
      more. These findings may be used to tailor physical activity interventions to
      women in rural communities.

PMID- 17182527
TI  - Obesity in low-income rural women: qualitative insights about physical activity
      and eating patterns.
AB  - Body weight is inversely related to socioeconomic status (SES) in women in the
      United States (U.S.). Reasons for the social differential in weight are poorly
      understood. This investigation sought to understand overweight and obesity from
      the perspective of low-income mothers living in rural New York State, focusing in
      particular on challenges to maintaining a healthy weight that may be unique to
      rural poverty. In-depth interviews with 28 women, who were interviewed 3 times
      over a 3-year period, were audiotaped, transcribed, and analyzed using the
      constant comparative method. Findings suggest that transportation difficulties
      confined some women to their homes, which were physical settings offering little
      opportunity for physical activity. Food insecurity and associated fluctuating
      household food supplies contributed to disordered eating patterns and to
      perceptions of dietary deprivation that affected food intake. Rural isolation
      contributed to negative emotional states that some women alleviated by eating.
      This research elucidates factors contributing to obesity among rural,
      economically disadvantaged women, highlighting the interplay between the
      structural constraints imposed by rural poverty and women's physical activity,
      eating patterns, body image, and weight. These insights further the understanding
      of social inequalities in health and could inform the design of future research
      aimed at improving the health status of low-income women and families.

PMID- 17182528
TI  - Healthy eating, exercise, and weight: impressions of sexual minority women.
AB  - Obesity is a risk factor for multiple disease outcomes, including cancer and
      cardiovascular disease. A healthy diet and physically active lifestyle can
      prevent obesity. Sexual orientation is an important demographic factor that has
      been suggested to affect engagement in health-related behaviors, and
      interventions developed for the general population of women are likely to be less
      effective in assisting sexual minority women to make healthy choices. We
      conducted seven focus groups with sexual minority women (i.e., lesbians and
      bisexual women) to explore issues, including barriers and motivations, regarding
      healthy eating, physical activity, and weight in this population. The
      participants reported a wide range of levels of engagement in health-related
      behaviors. While nearly all of the participants reported some awareness of the
      importance of good dietary choices, the majority reported some confusion about
      what constitutes a healthy diet. In contrast, the majority of participants seemed
      clearly aware that regular exercise was important for good health. These data can
      guide the design of effective intervention strategies to improve health behaviors
      in sexual minority women.

PMID- 17182529
TI  - Framing breastfeeding and formula-feeding messages in popular U.S. magazines.
AB  - Media framing of infant feeding has the ability to influence knowledge and views
      of the barriers, benefits, and solutions inherent in breastfeeding or formula
      feeding. This study examined how seven popular U.S. parenting, general women's,
      and African American magazines framed breastfeeding and formula-feeding messages
      to determine whether a sense-making approach was used and the extent to which
      visual images portrayed feeding practices. Analysis included 615 articles
      published from 1997 to 2003 that referred to infant feeding. Text and images were
      analyzed. The magazines provided more information on breastfeeding than formula
      feeding. Parenting magazines included more advice than barriers or benefits.
      African American magazines presented more breastfeeding benefits, and general
      women's magazines contained the least infant-feeding information. Messages were
      focused on individualized breastfeeding barriers and advice, seldom covered
      social and environmental issues, and placed much of the responsibility of infant
      feeding on the mother, while the role of social and partner support was
      diminished. Bottle-feeding images were nearly as common as breastfeeding images.
      Findings can be used by public health practitioners to increase the likelihood of
      reaching certain target audiences through popular magazines.

PMID- 17182530
TI  - Prisoners' perspectives of health problems and healthcare in a US women's jail.
AB  - In the last decade, the number of women in US jails has increased at an annual
      average of 7.0%. These women typically suffer from untreated, serious health
      problems. This participatory research project explored health problems and
      healthcare from the perspective of women incarcerated in a county detention
      facility located in the western US. A convenience sample of 78 inmates and former
      inmates participated in 10 focus groups. Using the constant comparative method,
      the data analysis revealed that they suffered from physical, mental, and
      iatrogenic health problems. Barriers to care included concerns about privacy and
      dignity as well as waiting time for treatment, co-payments, and concealing
      problems in order to obtain work opportunities. Women in the project identified
      solutions for these problems and analyzed why incarceration made them aware of
      previously ignored health concerns. The findings suggest the importance of
      further research with this vulnerable, hidden population.

PMID- 17182532
TI  - WNK4 kinase is a negative regulator of K+-Cl- cotransporters.
AB  - WNK kinases [with no lysine (K) kinase] are emerging as regulators of several
      membrane transport proteins in which WNKs act as molecular switches that
      coordinate the activity of several players. Members of the cation-coupled
      chloride cotransporters family (solute carrier family number 12) are one of the
      main targets. WNK3 activates the Na(+)-driven cotransporters NCC, NKCC1, and
      NKCC2 and inhibits the K(+)-driven cotransporters KCC1 to KCC4. WNK4 inhibits the
      activity of NCC and NKCC1, while in the presence of the STE20-related proline
      alanine-rich kinase SPAK activates NKCC1. Nothing is known, however, regarding
      the effect of WNK4 on the K(+)-Cl(-) cotransporters. Using the heterologous
      expression system of Xenopus laevis oocytes, here we show that WNK4 inhibits the
      activity of the K(+)-Cl(-) cotransporters KCC1, KCC3, and KCC4 under cell
      swelling, a condition in which these cotransporters are maximally active. The
      effect of WNK4 requires its catalytic activity because it was lost by the
      substitution of aspartate 318 for alanine (WNK4-D318A) that renders WNK4
      catalytically inactive. In contrast, three different WNK4 missense mutations that
      cause pseudohypoaldosteronism type II do not affect the WNK4-induced inhibition
      of KCC4. Finally, we observed that catalytically inactive WNK4-D318A is able to
      bypass the tonicity requirements for KCC2 and KCC3 activation in isotonic
      conditions. This effect is enhanced by the presence of catalytically inactive
      SPAK, was prevented by the presence of protein phosphatase inhibitors, and was
      not present in KCC1 and KCC4. Our results reveal that WNK4 regulates the activity
      of the K(+)-Cl(-) cotransporters expressed in the kidney.

PMID- 17182531
TI  - Identification of a novel signal in the cytoplasmic tail of the Na+:HCO3-
      cotransporter NBC1 that mediates basolateral targeting.
AB  - The Na(+):HCO(3)(-) cotransporter NBC1 (SLC4A4, variant A, kidney specific) is
      located exclusively on the basolateral membrane of epithelial cells, implying
      that this molecule has acquired specific signals for targeting to the basolateral
      membrane. A motif with the sequence QQPFLS (positions 1010-1015) in the
      cytoplasmic tail of NBC1 was recently demonstrated to mediate targeting of NBC1
      to the basolateral membrane. Here, we demonstrate that mutating the amino acid F
      (phenylalanine) or L (leucine) at positions 1013 or 1014 to alanine,
      respectively, resulted in the retargeting of NBC1 to the apical membrane.
      Furthermore, mutation of the FL motif to FF showed similar properties as the wild
      type; however, mutation of the FL motif to LL showed significant intracellular
      retention of NBC1. Mutating the amino acids Q-Q-P and S (positions 1010-1011-1012
      and 1015) to A-A-A and A, respectively, did not affect the membrane targeting of
      NBC1. Functional studies in oocytes with microelectrode demonstrated that the
      apically targeted mutants, as well as basolaterally targeted mutants, are all
      functional. We propose that the FL motif in the COOH-terminal tail of NBC1 is
      essential for the targeting of NBC1 to the basolateral membrane but is distinct
      from the membrane-targeting di-leucine motif identified in other membrane
      proteins.

PMID- 17182534
TI  - Pillars of immunology: The birth of a cell type.

PMID- 17182535
TI  - Pillars Article: Identification of a novel cell type in peripheral lymphoid
      organs of mice. I. Morphology, quantitation, tissue distribution. J. Exp.
      Med.1973. 137: 1142-1162.

PMID- 17182533
TI  - Renal compensation to chronic hypoxic hypercapnia: downregulation of pendrin and
      adaptation of the proximal tubule.
AB  - The molecular basis for the renal compensation to respiratory acidosis and
      specifically the role of pendrin in this condition are unclear. Therefore, we
      studied the adaptation of the proximal tubule and the collecting duct to
      respiratory acidosis. Male Wistar-Hannover rats were exposed to either
      hypercapnia and hypoxia [8% CO(2) and 13% O(2) (hypercapnic, n = 6) or normal air
      (controls, n = 6)] in an environmental chamber for 10 days and were killed under
      the same atmosphere. In hypercapnic rats, arterial pH was lower than controls
      (7.31 +/- 0.01 vs. 7.39 +/- 0.01, P = 0.03), blood HCO(3)(-) concentration was
      increased (42 +/- 0.9 vs. 32 +/- 0.24 mM, P < 0.001), arterial Pco(2) was
      increased (10.76 +/- 0.4 vs. 7.20 +/- 0.4 kPa, P < 0.001), and plasma chloride
      concentration was decreased (92.2 +/- 0.7 vs. 97.2 +/- 0.5 mM, P < 0.001). Plasma
      aldosterone levels were unchanged. In the proximal tubule, immunoblotting showed
      an increased expression of sodium/bicarbonate exchanger protein (188 +/- 22 vs.
      100 +/- 11%, P = 0.005), confirmed by immunohistochemistry. Total Na/H exchanger
      protein expression in the cortex was unchanged by immunoblotting (119 +/- 10 vs.
      100 +/- 11%, P = 0.27) and immunohistochemistry. In the cortex, the abundance of
      pendrin was decreased (51 +/- 9 vs. 100 +/- 7%, P = 0.003) by immunoblotting.
      Immunohistochemistry revealed that this decrease was clear in both cortical
      collecting ducts (CCDs) and connecting tubules (CNTs). This demonstrates that
      pendrin expression can be regulated in acidotic animals with no changes in
      aldosterone levels and no external chloride load. This reduction of pendrin
      expression may help in redirecting the CNT and CCD toward chloride excretion and
      bicarbonate reabsorption, contributing to the increased plasma bicarbonate and
      decreased plasma chloride of chronic respiratory acidosis.

PMID- 17182536
TI  - Roundtrip ticket for secretory IgA: role in mucosal homeostasis?
AB  - An important activity of mucosal surfaces is the production of Ab referred to as
      secretory IgA (SIgA). SIgA serves as the first line of defense against
      microorganisms through a mechanism called immune exclusion. In addition, SIgA
      adheres selectively to M cells in intestinal Peyer's patches, thus mediating the
      transepithelial transport of the Ab molecule from the intestinal lumen to
      underlying gut-associated organized lymphoid tissue. In Peyer's patches, SIgA
      binds and is internalized by dendritic cells in the subepithelial dome region.
      When used as carrier for Ags in oral immunization, SIgA induces mucosal and
      systemic responses associated with production of anti-inflammatory cytokines and
      limits activation of dendritic cells. In terms of humoral immunity at mucosal
      surfaces, SIgA appears thus to combine properties of a neutralizing agent (immune
      exclusion) and of a mucosal immunopotentiator inducing effector immune responses
      in a noninflammatory context favorable to preserve local homeostasis of the
      gastrointestinal tract.

PMID- 17182537
TI  - Cutting Edge: Allele-specific and peptide-dependent interactions between KIR3DL1
      and HLA-A and HLA-B.
AB  - Although it is clear that KIR3DL1 recognizes Bw4(+) HLA-B, the role of Bw4(+) HLA
      A allotypes as KIR3DL1 ligands is controversial. We therefore examined the
      binding of tetrameric HLA-A and -B complexes, including HLA*2402, a common Bw4(+)
      HLA-A allotype, to KIR3DL1*001, *005, *007, and *1502 allotypes. Only Bw4(+)
      tetramers bound KIR3DL1. Three of four HLA-A*2402 tetramers bound one or more
      KIR3DL1 allotypes and all four KIR3DL1 allotypes bound to one or more HLA-A*2402
      tetramers, but with different binding specificities. Only KIR3DL1*005 bound both
      HLA-A*2402 and HLA-B*5703 tetramers. HLA-A*2402-expressing target cells were
      resistant to lysis by NK cells expressing KIR3DL1*001 or *005. This study shows
      that HLA-A*2402 is a ligand for KIR3DL1 and demonstrates how the binding of
      KIR3DL1 to Bw4(+) ligands depends upon the bound peptide as well as HLA and
      KIR3DL1 polymorphism.

PMID- 17182538
TI  - GM-CSF production by autoreactive T cells is required for the activation of
      microglial cells and the onset of experimental autoimmune encephalomyelitis.
AB  - Multiple sclerosis (MS) is a CNS autoimmune disease believed to be triggered by T
      cells secreting Th1-specific proinflammatory cytokines, such as GM-CSF. In the
      animal model of MS, experimental autoimmune encephalomyelitis (EAE), Th1 but not
      Th2 cells have been shown to induce disease; however, to date, no single
      encephalitogenic T cell-derived cytokine has been shown to be required for EAE
      onset. Because GM-CSF-deficient mice have been shown to be resistant to EAE
      following immunization with myelin self-Ag, we investigated the cellular source
      of the required GM-CSF and found that GM-CSF production by encephalitogenic T
      cells, but not CNS resident or other peripheral cells, was required for EAE
      induction. Furthermore, we showed that microglial cell activation, but not
      peripheral macrophage activation, was a GM-CSF-dependent process. Activation of
      microglial cells by the injection of LPS abrogated the GM-CSF requirement for EAE
      induction, suggesting that microglial cell activation is required for EAE onset.
      These data also demonstrate that GM-CSF is a critical Th1 cell-derived cytokine
      required for the initiation of CNS inflammation associated with EAE, and likely
      MS.

PMID- 17182539
TI  - B cell lymphoma 10 is essential for FcepsilonR-mediated degranulation and IL-6
      production in mast cells.
AB  - The adaptor protein B cell lymphoma 10 (Bcl10) plays an essential role in the
      functions of the AgRs in T and B cells. In this study, we report that Bcl10 also
      plays an important role in mast cells. Bcl10 is expressed in mast cells. Although
      Bcl10-deficient mast cells undergo normal development, we demonstrate that Bcl10
      is essential for specific functions of FcepsilonR. Although Bcl10-deficient mast
      cells have normal de novo synthesis and release of the lipid mediator arachidonic
      acid, the mutant cells possess impaired FcepsilonR-mediated degranulation,
      indicated by decreased serotonin release, and impaired cytokine production,
      measured by release of IL-6. In addition, Bcl10-deficient mice display impaired
      IgE-mediated passive cutaneous anaphylaxis. Moreover, although Bcl10-deficient
      mast cells have normal FcepsilonR-mediated Ca(2+) flux, activation of PI3K, and
      activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells
      have markedly diminished FcepsilonR-mediated activation of NF-kappaB and
      decreased activation of AP-1. Thus, Bcl10 is essential for FcepsilonR-induced
      activation of AP-1, NF-kappaB, degranulation, and cytokine production in mast
      cells.

PMID- 17182540
TI  - Sensitivity of NK1.1-negative NKT cells to transgenic BATF defines a role for
      activator protein-1 in the expansion and maturation of immature NKT cells in the
      thymus.
AB  - NKT cells are glycolipid-reactive lymphocytes that express markers and perform
      functions common to both T lymphocytes and NK cells. Although the genetic events
      controlling conventional T cell development are well defined, the transcription
      factors and genetic programs regulating NKT cell development are only beginning
      to be elucidated. Previously, we described the NKT cell-deficient phenotype of
      transgenic (Tg) mice constitutively expressing B cell-activating transcription
      factor (BATF), a basic leucine zipper protein and inhibitor of AP-1. In this
      study, we show that Tg BATF targets the majority of Valpha14Jalpha281
      (Valpha14i(7)) NKT cells, regardless of CD4 expression and Vbeta gene usage. The
      residual NKT cells in the thymus of BATF-Tg mice are CD44(+), yet are slow to
      display the NK1.1 marker characteristic of mature cells. As a population, BATF
      expressing NKT cells are TCRbeta/CD3epsilon(low), but express normal levels of
      CD69, suggesting a failure to expand appropriately following selection.
      Consistent with the sensitivity of NKT cells to BATF-induced changes in AP-1
      activity, we detect a full complement of AP-1 basic leucine zipper proteins in
      wild-type NKT cells isolated from the thymus, spleen, and liver, and show that AP
      1 DNA-binding activity and cytokine gene transcription are induced in NKT cells
      within a few hours of glycolipid Ag exposure. This study is the first to
      characterize AP-1 activity in NKT cells and implicates the integrity of this
      transcription factor complex in developmental events essential to the
      establishment of this unique T cell subset in the thymus.

PMID- 17182541
TI  - Regulation of memory antibody levels: the role of persisting antigen versus
      plasma cell life span.
AB  - Protective Ab levels can be maintained for years upon infection or vaccination.
      In this study, we studied the duration of Ab responses as a function of the life
      span of plasma cells and tested the role of persisting Ag in maintaining B cell
      memory. Our analysis of B cell responses induced in mice immunized with virus
      like particles demonstrates the following: 1) Ab titers are long-lived, but
      decline continuously with a t(1/2) of approximately 80 days, which corresponds to
      the life span of plasma cells; 2) the germinal center (GC) reaction, which lasts
      for up to 100 days, is dependent on Ag associated with follicular dendritic
      cells; and 3) early GCs produce massive numbers of plasma and memory B cell
      precursors, whereas the late Ag-dependent GCs are dispensable for the maintenance
      of Ab levels and B cell memory.

PMID- 17182542
TI  - Granulysin-mediated tumor rejection in transgenic mice.
AB  - Granulysin (GNLY) is a cytolytic molecule expressed by human CTL and NK cells
      with activity against a variety of tumors and microbes, including Mycobacterium
      tuberculosis. Although the molecular mechanism of GNLY-induced apoptosis of
      Jurkat T cells is well defined in vitro, no direct evidence for its in vivo
      effects has been demonstrated. Because there is no murine homologue of GNLY, we
      generated mice expressing GNLY using a bacterial artificial chromosome containing
      the human GNLY gene and its 5' and 3' flanking regions. GNLY is expressed in
      leukocytes from transgenic mice with similar kinetics as in PBMC from humans:
      GNLY is constitutively expressed in NK cells and, following stimulation through
      the TCR, appears in T lymphocytes 8-10 days after activation. Both forms of GNLY
      (9 and 15 kDa) are produced by activated T cells, whereas the 15-kDa form
      predominates in freshly isolated NK cells from transgenic animals. GNLY mRNA is
      highest in spleen, with detectable expression in thymus and lungs, and minimal
      expression in heart, kidney, liver, muscle, intestine, and brain. Allospecific
      cell lines generated from GNLY transgenic animals showed enhanced killing of
      target cells. In vivo effects of GNLY were evaluated using the syngeneic T
      lymphoma tumor C6VL. GNLY transgenic mice survived significantly longer than
      nontransgenic littermates in response to a lethal tumor challenge. These findings
      demonstrate for the first time an in vivo effect of GNLY and suggest that GNLY
      may prove a useful therapeutic modality for the treatment of cancer.

PMID- 17182543
TI  - Tumor-primed human natural killer cells lyse NK-resistant tumor targets: evidence
      of a two-stage process in resting NK cell activation.
AB  - NK cells are defined as those cells that lyse tumor cells without priming. In
      this study, we show that the preincubation of resting human NK cells with the
      leukemia cell CTV-1 primes NK cells to lyse NK-resistant cell lines, primary
      leukemias, and solid tumors even when HLA-matched, allogeneic or autologous. The
      primed NK cells remained nonresponsive to HLA-C matched and mismatched normal
      mononuclear cells from multiple donors. CD69, a known NK trigger receptor, was
      shown to be the predominant trigger on the tumor-primed NK cells because lysis
      was blocked with the rCD69 protein. The lack of lytic activity against normal
      hemopoietic cells implied that the ligand for CD69 is tumor restricted, and this
      was confirmed by experiments using fluorochrome labeled rCD69. It has been
      recently shown that resting NK cells require prior stimulation with IL-2 before
      triggering by all known NK-triggering ligands. In this study, we show that a
      tumor cell can provide the NK priming signal independently of IL-2. These data
      provide evidence for two NK evasion strategies for tumor cells, namely the
      prevention of priming (type1 evasion) and failure to trigger (type 2 evasion).
      Most NK-resistant cell lines are type 1 and fail to prime resting NK cells but
      are lysed by IL-2-primed NK cells. In contrast, CTV-1 cells prime resting NK
      cells but fail to trigger (type 2), and coincubation with CTV-1 primes for
      triggering by type 1 NK-resistant tumor cells. These tumor-activated NK cells
      lyse a broad spectrum of tumor cells with a degree of specificity never
      previously reported.

PMID- 17182544
TI  - Apoptotic splenocytes drive the autoimmune response to poly(ADP-ribose)
      polymerase 1 in a murine model of lupus.
AB  - Although defects in apoptosis have been linked to both human and murine lupus,
      the exact mechanisms remain unknown. Moreover, it is not clear whether such
      defects are primary or secondary events in disease pathogenesis. To address these
      issues, we used an induced model of murine lupus, the parent-into-F(1) model of
      chronic graft-versus-host disease (cGVHD) in which a lupus-like phenotype highly
      similar to human systemic lupus erythematosus is reliably induced in normal F(1)
      mice. We addressed the role of nuclear Ags modified by caspases during apoptosis
      as potential targets of the autoantibody response and our results identify
      poly(ADP-ribose) polymerase 1 (PARP-1) as a frequently targeted autoantigen.
      Additional proteins cleaved during apoptosis were also targeted by the immune
      response. Importantly, female mice exhibited significantly greater numbers of
      apoptotic cells in germinal centers and higher serum anti-PARP-1 Ab levels
      compared with male cGVHD mice. Serum anti-PARP-1 levels in male cGVHD mice could
      be elevated to levels comparable to those of female cGVHD mice by the injection
      of apoptotic syngeneic F(1) splenocytes early in the disease course. These
      results provide a mechanism by which lupus autoantibodies target apoptotic
      molecules. Specifically, T cell-driven polyclonal B cell activation
      characteristic of systemic lupus erythematosus is sufficient to saturate
      otherwise normal apoptotic clearance mechanisms, permitting apoptotic material to
      accumulate, serve as autoantigens, and drive autoantibody production.

PMID- 17182545
TI  - Regulation of reactive oxygen species by Atm is essential for proper response to
      DNA double-strand breaks in lymphocytes.
AB  - The ataxia telangiectasia-mutated (ATM) gene plays a pivotal role in the
      maintenance of genomic stability. Although it has been recently shown that
      antioxidative agents inhibited lymphomagenesis in Atm(-/-) mice, the mechanisms
      remain unclear. In this study, we intensively investigated the roles of reactive
      oxygen species (ROS) in phenotypes of Atm(-/-) mice. Reduction of ROS by the
      antioxidant N-acetyl-l-cysteine (NAC) prevented the emergence of senescent
      phenotypes in Atm(-/-) mouse embryonic fibroblasts, hypersensitivity to total
      body irradiation, and thymic lymphomagenesis in Atm(-/-) mice. To understand the
      mechanisms for prevention of lymphomagenesis, we analyzed development of pretumor
      lymphocytes in Atm(-/-) mice. Impairment of Ig class switch recombination seen in
      Atm(-/-) mice was mitigated by NAC, indicating that ROS elevation leads to
      abnormal response to programmed double-strand breaks in vivo. Significantly, in
      vivo administration of NAC to Atm(-/-) mice restored normal T cell development
      and inhibited aberrant V(D)J recombination. We conclude that Atm-mediated ROS
      regulation is essential for proper DNA recombination, preventing
      immunodeficiency, and lymphomagenesis.

PMID- 17182546
TI  - Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B
      lymphoma growth.
AB  - Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma
      longa), has been shown in recent studies to have therapeutic potential in the
      treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the
      ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the
      growth of both murine and human B lymphoma in vitro and murine B lymphoma in
      vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma
      is through inhibition of the survival kinase Akt and its key target Bad. However,
      in vitro kinase assays show that Akt is not a direct target of curcumin. We
      identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase
      (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell
      lines and curcumin down-modulates Syk activity accompanied by down-regulation of
      Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or
      Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma
      cells. These observations suggest a novel growth promoting role for Syk in
      lymphoma cells.

PMID- 17182547
TI  - Activation of type B T cells after protein immunization reveals novel pathways of
      in vivo presentation of peptides.
AB  - Type B T cells recognize a peptide-MHC conformer generated in recycling endosomes
      and eliminated by H2-DM in late endosomes; as a result, they recognize exogenous
      peptide, but fail to respond to the identical epitope generated from the native
      protein. To investigate the behavior of these cells in vivo, we generated mice
      transgenic for a type B TCR recognizing the 48-62 epitope of hen egg white
      lysozyme (HEL) presented by I-A(k). Type B T cells responded only to peptide ex
      vivo, but responded in vivo to immunization with either protein or peptide in the
      presence of Freund's adjuvant or LPS. Presentation of the type B conformer was
      MyD88-independent, evident within 24 h after HEL immunization, and restricted to
      the CD11b/c(+) APC subset. Immunization with listeriolysin O, a potent inducer of
      cell death, also primed type B T cells in vivo, and transfer of HEL-bearing
      allogeneic dendritic cells activated type B T cells. We conclude that a number of
      conditions in vivo, some of which induce inflammation and cell death, lead to
      peptide presentation through mechanisms distinct from the classical pathways
      involving H-2DM molecules.

PMID- 17182548
TI  - Feedback regulation of murine autoimmunity via dominant anti-inflammatory effects
      of interferon gamma.
AB  - There is a paucity of knowledge concerning the immunologic sequelae that
      culminate in overt autoimmunity. In the present study, we have analyzed the
      factors that lead to disease in the model of autoimmunity, murine experimental
      autoimmune encephalomyelitis (EAE). EAE in H-2(u) mice involves autoreactive
      CD4(+) T cells that are induced by immunization with the immunodominant N
      terminal epitope of myelin basic protein. The affinity of this epitope for I-A(u)
      can be increased by substituting lysine at position 4 with tyrosine, and this can
      be used to increase the effective Ag dose. Paradoxically, high doses of Ag are
      poorly encephalitogenic. We have used quantitative analyses to study autoreactive
      CD4(+) T cell responses following immunization of mice with Ag doses that are at
      the extremes of encephalitogenicity. A dose of autoantigen that is poorly
      encephalitogenic results in T cell hyperresponsiveness, triggering an anti
      inflammatory feedback loop in which IFN-gamma plays a pivotal role. Our studies
      define a regulatory mechanism that serves to limit overly robust T cell
      responses. This feedback regulation has broad relevance to understanding the
      factors that determine T cell responsiveness.

PMID- 17182549
TI  - 1,25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid
      but not plasmacytoid dendritic cells.
AB  - 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is an immunomodulatory agent
      inducing dendritic cells (DCs) to become tolerogenic. To further understand its
      mechanisms of action, we have examined the effects of 1,25(OH)(2)D(3) on
      tolerogenic properties of blood myeloid (M-DCs) and plasmacytoid (P-DCs) human DC
      subsets. Exposure of M-DCs to 1,25(OH)(2)D(3) up-regulated production of CCL22, a
      chemokine attracting regulatory T cells, whereas production of CCL17, the other
      CCR4 ligand, was reduced. 1,25(OH)(2)D(3) also decreased IL-12p75 production by M
      DCs, as expected, and inhibited CCR7 expression. 1,25(OH)(2)D(3) treatment
      markedly increased CD4(+) suppressor T cell activity while decreasing the
      capacity of M-DCs to induce Th1 cell development. Surprisingly, 1,25(OH)(2)D(3)
      did not exert any discernible effect on tolerogenic properties of P-DCs, and even
      their high production of IFN-alpha was not modulated. In particular, the
      intrinsically high capacity of P-DCs to induce CD4(+) suppressor T cells was
      unaffected by 1,25(OH)(2)D(3). Both DC subsets expressed similar levels of the
      vitamin D receptor, and its ligation by 1,25(OH)(2)D(3) similarly activated the
      primary response gene cyp24. Interestingly, 1,25(OH)(2)D(3) inhibited NF-kappaB
      p65 phosphorylation and nuclear translocation in M-DCs but not P-DCs, suggesting
      a mechanism for the inability of 1,25(OH)(2)D(3) to modulate tolerogenic
      properties in P-DCs.

PMID- 17182550
TI  - Dectin-1 interaction with tetraspanin CD37 inhibits IL-6 production.
AB  - C-type lectins are pattern-recognition receptors important for pathogen binding
      and uptake by APCs. Evidence is accumulating that integration of incoming
      cellular signals in APCs is regulated by grouping of receptors and signaling
      molecules into organized membrane complexes, such as lipid rafts and tetraspanin
      microdomains. In this study, we demonstrate that C-type lectin dectin-1
      functionally interacts with leukocyte-specific tetraspanin CD37. Dectin-1 and
      CD37 colocalize on the surface of human APCs. Importantly, macrophages of CD37
      deficient (CD37(-/-)) mice express decreased dectin-1 membrane levels, due to
      increased dectin-1 internalization. Furthermore, transfection of CD37 into a
      macrophage cell line elevated endogenous dectin-1 surface expression. Although
      CD37 deficiency does not affect dectin-1-mediated phagocytosis, we observed a
      striking 10-fold increase of dectin-1-induced IL-6 production in CD37(-/-)
      macrophages compared with wild-type cells, despite reduced dectin-1 cell surface
      expression. Importantly, the observed increase in IL-6 production was specific
      for dectin-1, because signaling via other pattern-recognition receptors was
      unaffected in CD37(-/-) macrophages and because the dectin-1 ligand curdlan was
      used. Taken together, these findings show that tetraspanin CD37 is important for
      dectin-1 stabilization in APC membranes and controls dectin-1-mediated IL-6
      production.

PMID- 17182551
TI  - Genetic manipulation of CD74 in mouse strains of different backgrounds can result
      in opposite responses to central nervous system injury.
AB  - The ability to recover from CNS injuries is strain dependent. Transgenic mice
      that weakly express the p41 CD74 isoform (an integral membrane protein
      functioning as a MHC class II chaperone) on an I-A(b) genetic background have
      normal CD4(+) T cell populations and normal surface expression of MHC class II,
      but their B cell development is arrested while the cells are still immature.
      After a CNS injury, these mice recover better than their matched wild-type
      controls. We generated p41-transgenic mice on an I-A(d) background (p41-I-A(d)
      mice), and found that their recovery from CNS injuries was worse than that of
      controls. A correlative inverse effect was seen with respect to the kinetics of T
      cell and B cell recruitment to the injured CNS and the expression of insulin-like
      growth factor at the lesion site. These results, besides verifying previous
      findings that B cells function in the damaged CNS, demonstrate that the outcome
      of a particular genetic manipulation may be strain dependent.

PMID- 17182552
TI  - Th3 cells in peripheral tolerance. II. TGF-beta-transgenic Th3 cells rescue IL-2
      deficient mice from autoimmunity.
AB  - We developed a transgenic (Tg) mouse that expresses TGF-beta under control of the
      IL-2 promoter to investigate Th3 cell differentiation both in vitro and in vivo.
      We previously found that repetitive in vitro Ag stimulation results in constant
      expression of Foxp3 in TGF-beta-Tg Th3 cells that acquire regulatory function
      independent of surface expression of CD25. To examine the differentiation and
      function of Th3 cells in vivo and to compare them with thymic-derived
      CD4(+)CD25(+) regulatory T cells (Treg), we introduced the TGF-beta transgene
      into T cells of IL-2-deficient (IL-2(-/-)) mice. We found that the induction,
      differentiation, and function of TGF-beta-derived Foxp3(+) Th3 cells were
      independent of IL-2, which differs from thymic Tregs. In an environment that
      lacks functional CD25(+) thymic-derived Tregs, expression of the TGF-beta
      transgene in IL-2(-/-) mice led to the induction of distinct CD25(-) regulatory
      cells in the periphery. These cells expressed Foxp3 and efficiently controlled
      hyperproliferation of T cells and rescued the IL-2(-/-) mouse from lethal
      autoimmunity. Unlike IL-2(-/-) animals, TGF-beta/IL-2(-/-) mice had normal
      numbers of T cells, B cells, macrophages, and dendritic cells and did not have
      splenomegaly, lymphadenopathy, or inflammation in multiple organs. Accumulation
      of Foxp3(+) cells over time, however, was dependent on IL-2. Our results suggest
      that TGF-beta-derived Foxp3(+)CD25(+/-) Th3 regulatory cells represent a
      different cell lineage from thymic-derived CD25(+) Tregs in the periphery but may
      play an important role in maintaining thymic Tregs in the peripheral immune
      compartment by secretion of TGF-beta.

PMID- 17182553
TI  - Th3 cells in peripheral tolerance. I. Induction of Foxp3-positive regulatory T
      cells by Th3 cells derived from TGF-beta T cell-transgenic mice.
AB  - TGF-beta has been shown to be critical in the generation of CD4(+)CD25(+)Foxp3(+)
      regulatory T cells (Tregs). Because Th3 cells produce large amounts of TGF-beta,
      we asked whether induction of Th3 cells in the periphery was a mechanism by which
      CD4(+)CD25(+) Tregs were induced in the peripheral immune compartment. To address
      this issue, we generated a TGF-beta1-transgenic (Tg) mouse in which TGF-beta is
      linked to the IL-2 promoter and T cells transiently overexpress TGF-beta upon TCR
      stimulation but produce little or no IL-2, IL-4, IL-10, IL-13, or IFN-gamma.
      Naive TGF-beta-Tg mice are phenotypically normal with comparable numbers of
      lymphocytes and thymic-derived Tregs. We found that repeated antigenic
      stimulation of pathogenic myelin oligodendrocyte glycoprotein (MOG)-specific
      CD4(+)CD25(-) T cells from TGF-beta Tg mice crossed to MOG TCR-Tg mice induced
      Foxp3 expression in both CD25(+) and CD25(-) populations. Both CD25 subsets were
      anergic and had potent suppressive properties in vitro and in vivo. Furthermore,
      adoptive transfer of these induced regulatory CD25(+/-) T cells suppressed
      experimental autoimmune encephalomyelitis when administrated before disease
      induction or during ongoing experimental autoimmune encephalomyelitis. The
      suppressive effect of TGF-beta on T cell responses was due to the induction of
      Tregs and not to the direct inhibition of cell proliferation. The differentiation
      of Th3 cells in vitro was TGF-beta dependent as anti-TGF-beta abrogated their
      development. Thus, Ag-specific TGF-beta-producing Th3 cells play a crucial role
      in inducing and maintaining peripheral tolerance by driving the differentiation
      of Ag-specific Foxp3(+) regulatory cells in the periphery.

PMID- 17182554
TI  - Essential roles of c-Rel in TLR-induced IL-23 p19 gene expression in dendritic
      cells.
AB  - IL-23 plays crucial roles in both immunity against pathogens and autoimmunity
      against self. Although it is well recognized that IL-23 expression is restricted
      to the myeloid lineage and is tightly regulated at the transcriptional level, the
      nature of transcription factors required for IL-23 expression is poorly
      understood. We report, in this study, that murine dendritic cells deficient in c
      Rel, a member of the NF-kappaB family, are severely compromised in their ability
      to transcribe the p19 gene, one of the two genes that encode the IL-23 protein.
      The p19 gene promoter contains three putative NF-kappaB binding sites, two of
      which can effectively bind c-Rel as determined by chromatin immunoprecipitation
      and EMSA. Unexpectedly, mutation of either of these two c-Rel binding sites
      completely abolished the p19 promoter activity induced by five TLRs (2, 3, 4, 6,
      and 9) and four members of the NF-kappaB family (c-Rel, p65, p100, and p105).
      Based on these observations, we conclude that c-Rel controls IL-23 p19 gene
      expression through two kappaB sites in the p19 promoter, and propose a c-Rel
      dependent enhanceosome model for p19 gene activation.

PMID- 17182555
TI  - Osteoprotegerin reduces the serum level of receptor activator of NF-kappaB ligand
      derived from osteoblasts.
AB  - Osteoprotegerin (OPG) is a decoy receptor for receptor activator of NF-kappaB
      ligand (RANKL). We previously reported that OPG deficiency elevated the
      circulating level of RANKL in mice. Using OPG(-/-) mice, we investigated whether
      OPG is involved in the shedding of RANKL by cells expressing RANKL. Osteoblasts
      and activated T cells in culture released a large amount of RANKL in the absence
      of OPG. OPG or a soluble form of receptor activator of NF-kappaB (the receptor of
      RANKL) suppressed the release of RANKL from those cells. OPG- and T cell-double
      deficient mice showed an elevated serum RANKL level equivalent to that of OPG(-/
      ) mice, indicating that circulating RANKL is mainly derived from bone. The serum
      level of RANKL in OPG(-/-) mice was increased by ovariectomy or administration of
      1alpha,25-dihydroxyvitamin D(3). Expression of RANKL mRNA in bone, but not thymus
      or spleen, was increased in wild-type and OPG(-/-) mice by 1alpha,25
      dihydroxyvitamin D(3). These results suggest that OPG suppresses the shedding of
      RANKL from osteoblasts and that the serum RANKL in OPG(-/-) mice exactly reflects
      the state of bone resorption.

PMID- 17182556
TI  - alpha1beta1 Integrin+ and regulatory Foxp3+ T cells constitute two functionally
      distinct human CD4+ T cell subsets oppositely modulated by TNFalpha blockade.
AB  - The expression of the collagen receptor alpha(1)beta(1) integrin (VLA-1) on
      CD4(+) T cells is largely restricted to CCR7(-)CD45RO(+) cells that localize to
      inflamed tissues. Moreover, neutralizing alpha(1) integrin, in vivo, has been
      shown to compromise cell-mediated immunity. Our current study shows that the
      expression of VLA-1 on human CD4(+) T cells is restricted to conventional
      effectors. In contrast, Foxp3(+) T regulatory cells (Tregs) do not express this
      receptor. Moreover, Foxp3 or VLA-1 expression remained a mutually exclusive event
      in CD4(+) T cells even upon polyclonal anti-CD3-induced activation. Because
      TNFalpha blockade ameliorates certain T cell-dependent autoimmune disorders in
      humans, we investigated, in vitro, whether neutralizing TNFalpha affected the
      balance between the proinflammatory VLA-1(+) effectors and the counteracting
      Tregs. We found that anti-CD3 stimulation of freshly isolated PBL from healthy
      individuals, coupled with continuous TNFalpha blockade, inhibited the typical
      activation-dependent generation of CD4(+)VLA-1(+) Th1 cells. In contrast, it
      augmented the outgrowth of VLA-1(neg/dim)CD25(high) and Foxp3(+)CD4(+) T cells.
      Indeed, repeated anti-CD3 stimulation coupled with TNFalpha blockade generated
      CD4(+) T cell lines enriched for VLA-1(-)Foxp3(+) Tregs. Importantly, these
      CD4(+) T cells displayed potent suppressive functions toward autologous CD4(+)
      PBL, including the suppression of the activation-dependent induction of VLA-1(+)
      effectors. Thus, we propose a novel mechanism by which anti-TNFalpha therapy may
      restore self-tolerance, by shifting the balance between VLA-1(+) effectors and
      Foxp3(+) Tregs, during immune activation, in favor of the latter suppressor cell
      population.

PMID- 17182557
TI  - IFN-gamma negatively regulates CpG-induced IL-10 in bone marrow-derived dendritic
      cells.
AB  - Dendritic cells (DCs) are important players in the regulation of Th1- and Th2
      dominated immune responses. In these studies we showed that IFN-gamma, the key
      mediator of Th1 immunity, actively suppressed the production of IL-10 in murine
      DCs when activated with LPS or CpG. Our analysis revealed that both LPS and CpG
      induced IL-10 and IL-12 production but that the presence of IFN-gamma, in a dose
      dependent manner, suppressed the production of IL-10 while enhancing that of IL
      12. The observed inhibition of IL-10 production was independent of IL-12.
      Experiments performed with STAT-1 knockout mice demonstrated that the primary
      production of IL-12 induced by CpG was STAT-1 dependent, whereas the production
      of IL-10 was not. This finding was confirmed by the observation that CpG-induced
      IL-12 production could be inhibited by anti-IFN-beta Abs, whereas CpG-induced IL
      10 production could not be inhibited. These data also demonstrated that the
      inhibitory effect of IFN-gamma on IL-10 expression was STAT-1 dependent and
      transcriptionally regulated. Thus, DCs respond to CpG by producing
      proinflammatory and anti-inflammatory cytokines such as IL-12 and IL-10,
      respectively, and IFN-gamma acts to not only enhance IL-12 but also to inhibit IL
      10 production. The current data demonstrate a novel pathway for IFN-gamma
      mediated immunoregulation and suggest that IFN-gamma-dependent suppression of IL
      10 production by DCs may be involved in the antagonism between Th1 and Th2
      patterns of immune reactivity.

PMID- 17182558
TI  - Comparative roles of IL-4, IL-13, and IL-4Ralpha in dendritic cell maturation and
      CD4+ Th2 cell function.
AB  - IL-4 and IL-13 play key roles in Th2 immunity and asthma pathogenesis. Although
      the function of these cytokines is partially linked through their shared use of
      IL-4Ralpha for signaling, the interplay between these cytokines in the
      development of memory Th2 responses is not well delineated. In this
      investigation, we show that both IL-4 and IL-13 influence the maturation of
      dendritic cells (DC) in the lung and their ability to regulate secretion of IFN
      gamma and Th2 cytokines by memory CD4(+) T cells. Cocultures of wild-type T cells
      with pulmonary DC from allergic, cytokine-deficient mice demonstrated that IL-4
      enhanced the capacity of DC to stimulate T cell secretion of Th2 cytokines,
      whereas IL-13 enhanced the capacity of DC to suppress T cell secretion of IFN
      gamma. Because IL-4Ralpha is critical for IL-4 and IL-13 signaling, we also
      determined how variants of IL-4Ralpha influenced immune cell function. T cells
      derived from allergic mice expressing a high-affinity IL-4Ralpha variant produced
      higher levels of IL-5 and IL-13 compared with T cells derived from allergic mice
      expressing a low-affinity IL-4Ralpha variant. Although DC expressing different IL
      4Ralpha variants did not differ in their capacity to influence Th2 cytokine
      production, they varied in their capacity to inhibit IFN-gamma production by T
      cells. Thus, IL-4 and IL-13 differentially regulate DC function and the way these
      cells regulate T cells. The affinity of IL-4Ralpha also appears to be a
      determinant in the balance between Th2 and IFN-gamma responses and thus the
      severity of allergic disease.

PMID- 17182559
TI  - Role of the intracellular domain of IL-7 receptor in T cell development.
AB  - Signals from the IL-7R are uniquely required for T cell development and
      maintenance, despite the resemblance of IL-7R to other cytokine receptors and the
      apparent sharing of common signaling pathways. This unique requirement could
      either reflect unique expression of IL-7R or IL-7, or it could indicate that the
      IL-7R delivers unique signals. To determine whether the IL-7R provided unique
      signals, we exchanged its intracellular domain with that of other cytokine
      receptors: IL-4R, IL-9R, and prolactin receptor (PRLR). Chimeric receptors were
      used to reconstitute development of IL-7R(-/-) hemopoietic progenitors by
      transducing the receptors in retroviral vectors. Whereas IL-7R(-/-) thymocytes
      are arrested at the double-negative stage, IL-4R, IL-9R, or PRLR all imparted
      some progression to the double-positive stage. IL-4R and PRLR gave only small
      numbers of thymocytes, whereas IL-9R gave robust alphabeta T cell development and
      reconstitution of peripheral CD4 and CD8 cells, indicating that it can duplicate
      many of the functions of IL-7R. However, IL-9R failed to reconstitute
      rearrangement of the TCRgamma locus or development of gammadelta T cells. Thus,
      the IL-7R signals required in the alphabeta T cell lineage (such as survival and
      proliferation) are not unique to this receptor, whereas rearrangement of the
      TCRgamma locus may require a signal that is not shared by other receptors.

PMID- 17182560
TI  - Functional polymorphism of the KIR3DL1/S1 receptor on human NK cells.
AB  - NK cells express both inhibitory and activatory receptors that allow them to
      recognize target cells through HLA class I Ag expression. KIR3DL1 is a receptor
      that recognizes the HLA-Bw4 public epitope of HLA-B alleles. We demonstrate that
      polymorphism within the KIR3DL1 receptor has functional consequences in terms of
      NK cell recognition of target. Inhibitory alleles of KIR3DL1 differ in their
      ability to recognize HLA-Bw4 ligand, and a consistent hierarchy of ligand
      reactivity can be defined. KIR3DS1, which segregates as an allele of KIR3DL1, has
      a short cytoplasmic tail characteristic of activatory receptors. Because it is
      very similar to KIR3DL1 in the extracellular domains, it has been assumed that
      KIR3DS1 will recognize a HLA-Bw4 ligand. In this study, we demonstrate that
      KIR3DS1 is expressed as a protein at the cell surface of NK cells, where it is
      recognized by the Z27 Ab. Using this Ab, we found that KIR3DS1 is expressed on a
      higher percentage of NK cells in KIR3DS1 homozygous compared with heterozygous
      donors. In contrast to the inhibitory KIR3DL1 allotypes, KIR3DS1 did not
      recognize HLA-Bw4 on EBV-transformed cell lines.

PMID- 17182561
TI  - Cytokine-dependent Blimp-1 expression in activated T cells inhibits IL-2
      production.
AB  - After Ag activation of naive T cells in vitro, extensive growth and
      differentiation into effector cells depend upon IL-2. DNA microarray analysis was
      used to identify IL-2-dependent molecules regulating this process. In this study,
      we show that the transcriptional repressor B lymphocyte-induced maturation
      protein 1 (Blimp-1) is expressed by a cytokine-dependent pathway in activated T
      lymphocytes. IL-2 production by activated CD4(+) and CD8(+) T cells inversely
      correlated with Blimp-1 levels as higher IL-2 production was associated with
      lower Blimp-1 expression. Furthermore, ectopic expression of Blimp-1 by activated
      T cells inhibited IL-2 production but enhanced granzyme B and CD25 expression.
      Collectively, these findings indicate that there is a negative feedback
      regulatory loop in activated T cells such that IL-2 inhibits its own production
      through induction of Blimp-1 while promoting an effector cell phenotype.

PMID- 17182562
TI  - Multiple NF-kappaB and IFN regulatory factor family transcription factors
      regulate CCL19 gene expression in human monocyte-derived dendritic cells.
AB  - CCL19 chemokine has a central role in dendritic cell (DC) biology regulating DC
      traffic and recruitment of naive T cells to the vicinity of activated DCs. In
      this study, we have analyzed the regulation of CCL19 gene expression in human
      monocyte-derived DCs. DCs infected with Salmonella enterica or Sendai virus
      produced CCL19 at late times of infection. The CCL19 promoter was identified as
      having two putative NF-kappaB binding sites and one IFN-stimulated response
      element (ISRE). Transcription factor binding experiments demonstrated that
      Salmonella or Sendai virus infection increased the binding of classical p50+p65
      and alternative p52+RelB NF-kappaB proteins to both of the CCL19 promoter NF
      kappaB elements. Interestingly, Salmonella or Sendai virus infection also
      increased the binding of multiple IFN regulatory factors (IRFs), STAT1, and
      STAT2, to the ISRE element. Enhanced binding of IRF1, IRF3, IRF7, and IRF9 to the
      CCL19 promoter ISRE site was detected in Salmonella or Sendai virus-infected cell
      extracts. The CCL19 promoter in a luciferase reporter construct was activated by
      the expression of NF-kappaB p50+p65 or p52+RelB dimers. IRF1, IRF3, and IRF7
      proteins also activated CCL19 promoter in the presence of Sendai virus infection.
      CCL19 promoter constructs mutated at NF-kappaB and/or ISRE sites were only weakly
      activated. Ectopic expression of RIG-I (DeltaRIG-I, CARDIF) or TLR3/4 (TRIF,
      MyD88, IKKepsilon, or TBK1) signaling pathway components induced CCL19 promoter
      activity, suggesting that these pathways are important in CCL19 gene expression.
      Our experiments reveal that expression of the CCL19 gene is regulated by a
      combined action of several members of the NF-kappaB, IRF, and STAT family
      transcription factors.

PMID- 17182563
TI  - IL-7/STAT5 cytokine signaling pathway is essential but insufficient for
      maintenance of naive CD4 T cell survival in peripheral lymphoid organs.
AB  - Constitutive expression of suppressors of cytokine signaling (SOCS)1 in T lineage
      in vivo attenuated cytokine signaling and resulted in a dramatic reduction in the
      number of naive CD44(low)CD62L(high) CD4 T cells in the spleen. After adoptive
      transfer of thymocytes from SOCS1 transgenic mice into normal recipients, naive
      CD4 T cells rapidly disappeared from the spleen within 1 wk. Likewise, T cell
      specific deletion of STAT5a/b in vivo resulted in a similar phenotype
      characterized by loss of naive CD4 T cells. Thus, STAT5-mediated signaling is
      crucial for promoting naive T cell survival. However, forced expression of
      constitutively active STAT5 failed to rescue CD4 T cells in SOCS1 transgenic
      mice, implying that STAT5 activation is necessary but not sufficient for naive
      CD4 T cell survival. Although blockade of the IL-7R, a SOCS1 target, resulted in
      clear inhibition of naive T cell survival, the effect occurred 3 wk after anti-IL
      7R Ab treatment, but not at earlier time points. These results suggest that IL-7
      mediated STAT5 activation is essential for long-term survival of naive CD4 cells
      after export from thymus, and that another SOCS1-sensitive cytokine is critical
      for short-term naive T cell survival.

PMID- 17182564
TI  - IL-6 produced by dendritic cells from lupus-prone mice inhibits CD4+CD25+ T cell
      regulatory functions.
AB  - The B6.Sle1.Sle2.Sle3 triple congenic mouse (B6.TC) is a model of lupus
      coexpressing the three major NZM2410-derived susceptibility loci on a C57BL/6
      background. B6.TC mice produce high titers of antinuclear nephrogenic
      autoantibodies and a highly penetrant glomerulonephritis. Previous studies have
      shown the Sle1 locus is associated with a reduced number of regulatory T cells
      (Treg) and that Sle3 results in intrinsic defects of myeloid cells that
      hyperactivate T cells. In this report, we show that B6.TC dendritic cells (DCs)
      accumulate in lymphoid organs and present a defective maturation process, in
      which bone marrow-derived, plasmacytoid, and myeloid DCs express a significantly
      lower level of CD80, CD86, and MHC class II. B6.TC DCs also induce a higher level
      of proliferation in CD4(+) T cells than B6 DCs, and B6.TC DCs block the
      suppressive activity of Treg. B6.TC DCs overproduce IL-6, which is necessary for
      the blockade of Treg activity, as shown by the effect of anti-IL-6 neutralizing
      Ab in the suppression assays. The overproduction of IL-6 by DCs and the blockade
      of Treg activity maps to Sle1, which therefore not only confers a reduced number
      of Treg but also blocks their ability to regulate autoreactive T cells. Taken
      together, these results provide a genetic and mechanistic evidence for systemic
      autoimmunity resulting from an impaired regulatory T cell compartment in both
      number and function and for Sle1-expressing DCs playing a major role in the
      latter defect though their production of IL-6.

PMID- 17182565
TI  - IL-2 receptor beta-dependent STAT5 activation is required for the development of
      Foxp3+ regulatory T cells.
AB  - IL-2(-/-) mice develop autoimmunity despite having relatively normal numbers of
      regulatory T cells (Tregs). In contrast, we demonstrate that IL-2(-/-) x IL-15(-/
      ) and IL-2Rbeta(-/-) mice have a significant decrease in Treg numbers. Ectopic
      expression of foxp3 in a subset of CD4(+) T cells rescued Treg development and
      prevented autoimmunity in IL-2Rbeta(-/-) mice, suggesting that IL-2Rbeta
      dependent signals regulate foxp3 expression in Tregs. Subsequent analysis of IL
      2Rbeta-dependent signal transduction pathways established that the transcription
      factor STAT5 is necessary and sufficient for Treg development. Specifically, T
      cell-specific deletion of STAT5 prevented Treg development; conversely,
      reconstitution of IL-2Rbeta(-/-) mice with bone marrow cells expressing an IL
      2Rbeta mutant that exclusively activates STAT5 restored Treg development.
      Finally, STAT5 binds to the promoter of the foxp3 gene suggesting that IL-2Rbeta
      dependent STAT5 activation promotes Treg differentiation by regulating expression
      of foxp3.

PMID- 17182566
TI  - CD25+CD4+ regulatory T cell migration requires L-selectin expression: L-selectin
      transcriptional regulation balances constitutive receptor turnover.
AB  - The molecular mechanisms controlling regulatory CD25(+)Foxp3(+)CD4(+) T cell
      (T(reg)) migration are central to in vivo immune responses. T(reg) cell subsets
      differentially express L-selectin, an adhesion molecule mediating lymphocyte
      migration to peripheral LNs (PLNs) and leukocyte rolling during inflammation. In
      this study, L-selectin was essential for T(reg) cell migration and normal tissue
      distribution. Specifically, there was a 90% reduction in PLN T(reg) cells in L
      selectin(-/-) mice with a compensatory increase in spleen T(reg) cell numbers.
      Unexpectedly, however, 40% of the CD4(+) T cells remaining within PLNs of L
      selectin(-/-) mice were T(reg) cells. The migratory properties of T(reg) cells
      were nonetheless markedly different from those of naive CD4(+) T cells, with 3-
      to 9-fold lower migration of T(reg) cells into PLNs and approximately 2-fold
      lower migration into the spleen. T(reg) cells also turned over cell surface L
      selectin at a faster rate than CD25(-)CD4(+) T cells, but maintained
      physiologically appropriate L-selectin densities for optimal migration.
      Specifically, T(reg) cells expressed 30-40% more cell surface L-selectin when its
      endoproteolytic cleavage was blocked genetically, which resulted in a 2-fold
      increase in T(reg) cell migration into PLNs. However, increased L-selectin
      cleavage by T(reg) cells in wild-type mice was accompanied by 2-fold higher L
      selectin mRNA levels, which resulted in equivalent cell surface L-selectin
      densities on T(reg) and naive T cells. Thus, T(reg) cells and CD25(-)CD4(+) T
      cells share similar requirements for L-selectin expression during migration,
      although additional molecular mechanisms constrain T(reg) cell migration beyond
      what is required for naive CD4(+) T cell migration.

PMID- 17182567
TI  - FoxP3+ T cells undergo conventional first switch to lymphoid tissue homing
      receptors in thymus but accelerated second switch to nonlymphoid tissue homing
      receptors in secondary lymphoid tissues.
AB  - Forkhead box P3 (FoxP3)-positive T cells are a specialized T cell subset for
      immune regulation and tolerance. We investigated the trafficking receptor
      switches of FoxP3(+) T cells in thymus and secondary lymphoid tissues and the
      functional consequences of these switches in migration. We found that FoxP3(+) T
      cells undergo two discrete developmental switches in trafficking receptors to
      migrate from primary to secondary and then to nonlymphoid tissues in a manner
      similar to conventional CD4(+) T cells as well as unique to the FoxP3(+) cell
      lineage. In the thymus, precursors of FoxP3(+) cells undergo the first
      trafficking receptor switch (CCR8/CCR9-->CXCR4-->CCR7), generating mostly
      homogeneous CD62L(+)CCR7(+)CXCR4(low)FoxP3(+) T cells. CXCR4 expression is
      regained in FoxP3(+) thymic emigrants in the periphery. Consistent with this
      switch, recent FoxP3(+) thymic emigrants migrate exclusively to secondary
      lymphoid tissues but poorly to nonlymphoid tissues. The FoxP3(+) thymic emigrants
      undergo the second switch in trafficking receptors for migration to nonlymphoid
      tissues upon Ag priming. This second switch involves down-regulation of CCR7 and
      CXCR4 but up-regulation of a number of memory/effector type homing receptors,
      resulting in generation of heterogeneous FoxP3(+) T cell subsets expressing
      various combinations of trafficking receptors including CCR2, CCR4, CCR6, CCR8,
      and CCR9. A notable difference between the FoxP3(+) and FoxP3(-) T cell
      populations is that FoxP3(+) T cells undergo the second homing receptor switch at
      a highly accelerated rate compared with FoxP3(-) T cells, generating FoxP3(+) T
      cells with unconventionally efficient migratory capacity to major nonlymphoid
      tissues.

PMID- 17182568
TI  - The critical role of protein kinase C-theta in Fas/Fas ligand-mediated apoptosis.
AB  - A functional immune system not only requires rapid expansion of antigenic
      specific T cells, but also requires efficient deletion of clonally expanded T
      cells to avoid accumulation of T cells. Fas/Fas ligand (FasL)-mediated apoptosis
      plays a critical role in the deletion of activated peripheral T cells, which is
      clearly demonstrated by superantigen-induced expansion and subsequent deletion of
      T cells. In this study, we show that in the absence of protein kinase C-theta
      (PKC-theta), superantigen (staphylococcal enterotoxin B)-induced deletion of
      Vbeta8(+) CD4(+) T cells was defective in PKC-theta(-/-) mice. In response to
      staphylococcal enterotoxin B challenge, up-regulation of FasL, but not Fas, was
      significantly reduced in PKC-theta(-/-) mice. PKC-theta is thus required for
      maximum up-regulation of FasL in vivo. We further show that stimulation of FasL
      expression depends on PKC-theta-mediated activation of NF-AT pathway. In
      addition, PKC-theta(-/-) T cells displayed resistance to Fas-mediated apoptosis
      as well as activation-induced cell death (AICD). In the absence of PKC-theta, Fas
      induced activation of apoptotic molecules such as caspase-8, caspase-3, and Bid
      was not efficient. However, AICD as well as Fas-mediated apoptosis of PKC-theta(
      /-) T cells were restored in the presence of high concentration of IL-2, a
      critical factor required for potentiating T cells for AICD. PKC-theta is thus
      required for promoting FasL expression and for potentiating Fas-mediated
      apoptosis.

PMID- 17182569
TI  - Selective survival of naturally occurring human CD4+CD25+Foxp3+ regulatory T
      cells cultured with rapamycin.
AB  - Naturally occurring CD4(+)CD25(+) regulatory T (nTreg) cells are essential for
      maintaining T cell tolerance to self Ags. We show that discrimination of human
      Treg from effector CD4(+)CD25(+) non-nTreg cells and their selective survival and
      proliferation can now be achieved using rapamycin (sirolimus). Human purified
      CD4(+)CD25(high) T cell subsets stimulated via TCR and CD28 or by IL-2 survived
      and expanded up to 40-fold in the presence of 1 nM rapamycin, while
      CD4(+)CD25(low) or CD4(+)CD25(-) T cells did not. The expanding pure populations
      of CD4(+)CD25(high) T cells were resistant to rapamycin-accelerated apoptosis. In
      contrast, proliferation of CD4(+)CD25(-) T cells was blocked by rapamycin, which
      induced their apoptosis. The rapamycin-expanded CD4(+)CD25(high) T cell
      populations retained a broad TCR repertoire and, like CD4(+) CD25(+) T cells
      freshly obtained from the peripheral circulation, constitutively expressed CD25,
      Foxp3, CD62L, glucocorticoid-induced TNFR family related protein, CTLA-4, and CCR
      7. The rapamycin-expanded T cells suppressed proliferation and effector functions
      of allogeneic or autologous CD4(+) and CD8(+) T cells in vitro. They equally
      suppressed Ag-specific and nonspecific responses. Our studies have defined ex
      vivo conditions for robust expansion of pure populations of human nTreg cells
      with potent suppressive activity. It is expected that the availability of this
      otherwise rare T cell subset for further studies will help define the molecular
      basis of Treg-mediated suppression in humans.

PMID- 17182570
TI  - Loss of Src homology region 2 domain-containing protein tyrosine phosphatase-1
      increases CD8+ T cell-APC conjugate formation and is associated with enhanced in
      vivo CTL function.
AB  - Extensive evidence has been accumulated to implicate the intracellular protein
      tyrosine phosphatase, Src homology region 2 domain-containing protein tyrosine
      phosphatase-1 (SHP-1), as a negative regulator of TCR-signaling thresholds.
      Specifically, T cells from the SHP-1-deficient mouse, motheaten, exhibit a
      hyperproliferative phenotype when activated by cognate peptide-pulsed APCs.
      However, the cellular basis for this phenotype has not been fully explained.
      Using the intracellular fluorescent dye, CFSE, we show that a greater proportion
      of motheaten vs control naive CD8(+) T cells undergo cell division when activated
      by peptide-pulsed APCs. Furthermore, there is a greater likelihood of TCRs on SHP
      1-deficient vs control T cells binding to peptide/MHC ligands on APCs when using
      TCR down-regulation as an indirect measure of TCR engagement. In addition, T cell
      APC conjugate assays provide direct evidence that a greater proportion of SHP-1
      deficient T cells are capable of forming stable conjugates with APCs and this may
      explain, at least in part, their hyperproliferative response to TCR-triggered
      stimulation. The physiological relevance of the combined in vitro observations is
      demonstrated by the significantly enhanced in vivo expansion and CTL capacity
      generated in mice receiving adoptively transferred SHP-1-deficient naive CD8(+) T
      cells when compared with control T cells.

PMID- 17182571
TI  - Mycobacterium leprae inhibits dendritic cell activation and maturation.
AB  - Leprosy presents with a clinical spectrum of skin lesions that span from strong
      Th1-mediated cellular immunity and control of bacillary growth at one pole to
      poor Ag-specific T cell immunity with extensive bacillary load and Th2 cytokine
      expressing lesions at the other. To understand how the immune response to
      Mycobacterium leprae is regulated, human dendritic cells (DC), potent inducers of
      adaptive immune responses, exposed to M. leprae, Mycobacterium tuberculosis
      (Mtb), and Mycobacterium bovis bacillus Calmette-Guerin (BCG) were studied for
      their ability to be activated and to prime T cell proliferation. In contrast with
      Mtb and BCG, M. leprae did not induce DC activation/maturation as measured by the
      expression of selected surface markers and proinflammatory cytokine production.
      In MLR, T cells did not proliferate in response to M. leprae-stimulated DC.
      Interestingly, M. leprae-exposed MLR cells secreted increased Th2 cytokines as
      well as similar Th1 cytokine levels as compared with Mtb- and BCG-exposed cells.
      Gene expression analysis revealed a reduction in levels of mRNA of DC activation
      and maturation markers following exposure to M. leprae. Our data suggest that M.
      leprae does not induce and probably suppresses in vitro DC maturation/activation,
      whereas Mtb and BCG are stimulatory.

PMID- 17182572
TI  - Brahma-related gene 1-dependent STAT3 recruitment at IL-6-inducible genes.
AB  - IL-6 is an immunoregulatory cytokine with multiple functions in hemopoiesis,
      proliferation, and tumorigenesis. IL-6 triggers phosphorylation, dimerization,
      and nuclear translocation of STAT3, which binds to target promoters and activates
      transcription. Brahma-related gene 1 (BRG1), the enzymatic engine of the yeast
      mating type-switching and sucrose-nonfermenting chromatin-remodeling complex, is
      essential for recruitment of STAT1 or STAT1/STAT2-containing complexes to IFN
      targets. We hypothesized that BRG1 might also be required for STAT3 recruitment.
      In this study, we show that induction of a subset of human IL-6-responsive genes
      is BRG1 dependent. BRG1 is constitutively present at these targets and is
      required for STAT3 recruitment, downstream histone modifications, and IL-6
      induced chromatin remodeling. IL-6-induced recruitment of STAT3 to the IFN
      regulatory factor 1 promoter and subsequent mRNA synthesis is BRG1 dependent,
      even though IFN-gamma-mediated STAT1 recruitment to this locus is BRG1
      independent. BRG1 also increased basal expression of IFN-induced transmembrane
      protein 3 and IFN-gamma-induced protein 16, and the basal chromatin accessibility
      at the promoter of IFN regulatory factor 1. The effect on basal expression was
      STAT3 independent, as revealed by small interfering RNA knockdown. Together with
      prior observations, these data reveal that BRG1 has a broad role in mediating
      STAT accessibility at multiple cytokine-responsive promoters and exposes promoter
      specific differences in both the effect of BRG1 on basal chromatin accessibility
      and on access of different STAT proteins to the same target.

PMID- 17182573
TI  - Decay-accelerating factor must bind both components of the complement alternative
      pathway C3 convertase to mediate efficient decay.
AB  - Decay-accelerating factor (DAF; CD55) inhibits the complement (C) cascade by
      dissociating the multimolecular C3 convertase enzymes central to amplification.
      We have previously demonstrated using surface plasmon resonance (Biacore
      International) that DAF mediates decay of the alternative pathway C3 convertase,
      C3bBb, but not of the inactive proenzyme, C3bB, and have shown that the major
      site of interaction is with the larger cleavage subunit factor B (Bb) subunit. In
      this study, we dissect these interactions and demonstrate that the second short
      consensus repeat (SCR) domain of DAF (SCR2) interacts only with Bb, whereas SCR4
      interacts with C3b. Despite earlier studies that found SCR3 to be critical to DAF
      activity, we find that SCR3 does not directly interact with either subunit.
      Furthermore, we demonstrate that properdin, a positive regulator of the
      alternative pathway, does not directly interact with DAF. Extending from studies
      of binding to decay-accelerating activity, we show that truncated forms of DAF
      consisting of SCRs 2 and 3 bind the convertase stably via SCR2-Bb interactions
      but have little functional activity. In contrast, an SCR34 construct mediates
      decay acceleration, presumably due to SCR4-C3b interactions demonstrated above,
      because SCR3 alone has no binding or functional effect. We propose that DAF
      interacts with C3bBb through major sites in SCR2 and SCR4. Binding to Bb via SCR2
      increases avidity of binding, concentrating DAF on the active convertase, whereas
      more transient interactions through SCR4 with C3b directly mediate decay
      acceleration. These data provide new insights into the mechanisms involved in C3
      convertase decay by DAF.

PMID- 17182574
TI  - Essential role of GATA transcriptional factors in the activation of mast cells.
AB  - Mast cells are pivotal effector cells in IgE-mediated allergic reactions. GATA
      transcriptional factors such as GATA-1 and GATA-2 are expressed in mast cells,
      and recent studies have revealed that both GATA-1 and GATA-2 are required for
      mast cell development. However, the role of GATA transcriptional factors in
      differentiated mast cells has remained largely unknown. In this study, we
      repressed the activity of GATA-1 and GATA-2 by using three different approaches
      (inducible overexpression of a dominant-negative form of GATA, pharmacological
      inactivation, or small interfering RNA technology), and analyzed the molecular
      mechanisms of GATA transcriptional factors in the activation of mast cells.
      Surprisingly, the repression of GATA activity in differentiated mast cells led to
      the impairment of cell survival, IgE-induced degranulation, and cytokine
      production. Signal transduction and histone modification in the chromatin related
      to protein kinase Cbeta were defective in these cells. These results identify
      that GATA has a critical role in the activation of mast cell.

PMID- 17182575
TI  - Critical residues at the Ly49 natural killer receptor's homodimer interface
      determine functional recognition of m157, a mouse cytomegalovirus MHC class I
      like protein.
AB  - NK cell function is regulated by Ly49 receptors in mice and killer cell Ig-like
      receptors in humans. Although inhibitory Ly49 and killer cell Ig-like receptors
      predominantly ligate classical MHC class I molecules, recent studies suggest that
      their activating counterparts recognize infection. The quintessential example is
      resistance to the mouse CMV in C57BL/6 mice, which depends on the functional
      recognition of m157, a mouse CMV-encoded MHC class I-like molecule, by Ly49H, an
      activating NK cell receptor. We have taken advantage of the natural variation in
      closely related members of the Ly49C-like receptors and the availability of Ly49
      crystal structures to understand the molecular determinants of the Ly49H-m157
      interaction and to identify amino acid residues discriminating between m157
      binding and nonbinding receptors. Using a site-directed mutagenesis approach, we
      have targeted residues conserved in receptors binding to m157 (Ly49H and
      Ly49I(129)) but different from receptors lacking m157 recognition (Ly49C,
      Ly49I(B6), and Ly49U). Wild-type and mutant receptors were transfected into
      reporter cells, and physical binding as well as functional activation by m157 was
      studied. Our findings suggested that the Ly49 MHC class I contact "site 2," I226,
      may not be involved in m157 binding. In contrast, residue Y146 and G151, mapping
      at the receptor homodimer interface, are likely critical for functional
      recognition of the m157 glycoprotein. Our combined functional and three
      dimensional modeling approach suggested that the architecture of the Ly49H dimer
      is crucial to accessing m157, but not MHC class I. These results link Ly49
      homodimerization variability to the direct recognition of pathogen products.

PMID- 17182576
TI  - Distinct and shared transcriptomes are regulated by microphthalmia-associated
      transcription factor isoforms in mast cells.
AB  - The Microphthalmia-associated transcription factor (Mitf) is an essential basic
      helix-loop-helix leucine zipper transcription factor for mast cell development.
      Mice deficient in Mitf harbor a severe mast cell deficiency, and Mitf-mutant mast
      cells cultured ex vivo display a number of functional defects. Therefore, an
      understanding of the genetic program regulated by Mitf may provide important
      insights into mast cell differentiation. Multiple, distinct isoforms of Mitf have
      been identified in a variety of cell types; we found that Mitf-a, Mitf-e, and
      Mitf-mc were the major isoforms expressed in mast cells. To determine the
      physiologic function of Mitf in mast cells, we restored expression of these
      isoforms in primary mast cells from Mitf(-/-) mice. We found that these isoforms
      restored granular morphology and integrin-mediated migration. By microarray
      analysis, proteases, signaling molecules, cell surface receptor, and transporters
      comprised the largest groups of genes up-regulated by all isoforms. Furthermore,
      we found that isoforms also regulated distinct genes sets, suggesting separable
      biological activities. This work defines the transcriptome regulated by Mitf in
      mast cells and supports its role as master regulator of mast cell
      differentiation. Expression of multiple isoforms of this transcription factor may
      provide for redundancy of biological activities while also allowing diversity of
      function.

PMID- 17182577
TI  - Cross-reactivity and 1.4-A crystal structure of Malassezia sympodialis
      thioredoxin (Mala s 13), a member of a new pan-allergen family.
AB  - We have identified thioredoxins (Trx) of Malassezia sympodialis, a yeast involved
      in the pathogenesis of atopic eczema, and of Aspergillus fumigatus, a fungus
      involved in pulmonary complications, as novel IgE-binding proteins. We show that
      these Trx, including the human enzyme, represent cross-reactive structures
      recognized by serum IgE from individuals sensitized to M. sympodialis Trx.
      Moreover, all three proteins were able to elicit immediate-type allergic skin
      reactions in sensitized individuals, indicating a humoral immune response based
      on molecular mimicry. To analyze structural elements involved in these reactions,
      the three-dimensional structure of M. sympodialis Trx (Mala s 13) has been
      determined at 1.4-A resolution by x-ray diffraction analysis. The structure was
      solved by molecular replacement and refined to a crystallographic R factor of
      14.0% and a free R factor of 16.8% and shows the typical Trx fold. Mala s 13
      shares 45% sequence identity with human Trx and superposition of the solved Mala
      s 13 structure with those of human Trx reveals a high similarity with a root mean
      square deviation of 1.11 A for all Calpha atoms. In a detailed analysis of the
      molecular surface in combination with sequence alignment, we identified conserved
      solvent-exposed amino acids scattered over the surface in both structures which
      cluster to patches, thus forming putative conformational B cell epitopes
      potentially involved in IgE-mediated cross- and autoreactivity.

PMID- 17182578
TI  - Lamprey TLRs with properties distinct from those of the variable lymphocyte
      receptors.
AB  - Fish express mammalian-type (M-type) TLRs consisting of leucine-rich repeats
      (LRRs) and Toll-IL-1R (TIR) homology domain for immunity, whereas invertebrates
      in deuterostomes appear to have no orthologs of M-type TLRs. Lampetra japonica
      (lamprey) belongs to the lowest class of vertebrates with little information
      about its TLRs. We have identified two cDNA sequences of putative TLRs in the
      lamprey (laTLRs) that contain LRRs and TIR domains. The two laTLRs were 56%
      homologous to each other, and their TIRs were similar to those of members of the
      human TLR2 subfamily, most likely orthologs of fish TLR14. We named them laTLR14a
      and laTLR14b. We raised a rabbit polyclonal Ab against laTLR14b and identified a
      85-kDa protein in a human HEK293 transfectant by immunoblotting using the Ab.
      FACS, histochemical, and confocal analyses showed that laTLR14b is expressed
      intracellularly in lamprey gill cells and that the overexpressed protein resides
      in the endoplasmic reticulum of human and fish (medaka) cell lines. Because
      natural agonists of TLR14 remained unidentified, we made a chimera construct of
      extracellular CD4 and the cytoplasmic domain of laTLR14. The chimera molecule of
      laTLR14b, when expressed in HEK293 cells, elicited activation of NF-kappaB and,
      consequently, weak activation of the IFN-beta promoter. laTLR14b mRNA was
      observed in various organs and leukocytes. This lamprey species expressed a
      variable lymphocyte receptor structurally independent of laTLR14 in leukocytes.
      Thus, the jawless vertebrate lamprey possesses two LRR-based recognition systems,
      the variable lymphocyte receptor and TLR, and the M-type TLRs are conserved
      across humans, fish, and lampreys.

PMID- 17182579
TI  - IL-22 participates in an innate anti-HIV-1 host-resistance network through acute
      phase protein induction.
AB  - Certain individuals are resistant to HIV-1 infection, despite repeated exposure
      to the virus. Although protection against HIV-1 infection in a small proportion
      of Caucasian individuals is associated with mutant alleles of the CCR5 HIV-1
      coreceptor, the molecular mechanism underlying resistance in repeatedly HIV-1
      exposed, uninfected individuals (EU) is unclear. In this study, we performed
      complementary transcriptome and proteome analyses on peripheral blood T cells,
      and plasma or serum from EU, their HIV-1-infected sexual partners, and healthy
      controls, all expressing wild-type CCR5. We report that activated T cells from EU
      overproduce several proteins involved in the innate immunity response,
      principally those including high levels of peroxiredoxin II, a NK-enhancing
      factor possessing strong anti-HIV activity, and IL-22, a cytokine involved in the
      production of acute-phase proteins such as the acute-phase serum amyloid A (A
      SAA). Cell supernatants and serum levels of these proteins were up-regulated in
      EU. Moreover, a specific biomarker for EU detected in plasma was identified as an
      8.6-kDa A-SAA cleavage product. Incubation of in vitro-generated myeloid immature
      dendritic cells with A-SAA resulted in CCR5 phosphorylation, down-regulation of
      CCR5 expression, and strongly decreased susceptibility of these cells to in vitro
      infection with a primary HIV-1 isolate. Taken together, these results suggest new
      correlates of EU protection and identify a cascade involving IL-22 and the acute
      phase protein pathway that is associated with innate host resistance to HIV
      infection.

PMID- 17182580
TI  - Regulation of leukocyte degranulation by cGMP-dependent protein kinase and
      phosphoinositide 3-kinase: potential roles in phosphorylation of target membrane
      SNARE complex proteins in rat mast cells.
AB  - We examined the roles of cGMP-dependent protein kinase (PKG) and PI3K in
      degranulation induced by fMLF and by FcepsilonRI cross-linking. In rat basophilic
      leukemia-2H3 cells expressing formyl peptide receptor, the PKG inhibitors KT5823
      and Rp-8-Br-PET-cGMP, as well as the PI3K inhibitor LY294002, reduced agonist
      stimulated beta-hexosaminidase release in a dose-dependent manner. These
      inhibitors also abolished vesicular fusion with the plasma membrane, as evidenced
      by diminished annexin V staining. Agonist-induced degranulation was completely
      blocked when LY294002 was applied together with one of the PKG inhibitors,
      suggesting an additive and possibly synergistic effect. In contrast, the PKG
      inhibitors did not affect fMLF-induced intracellular calcium mobilization and Akt
      phosphorylation. Likewise, LY294002 did not alter fMLF-induced elevation of
      intracellular cGMP concentration, and the inhibitory effect of LY294002 was not
      reversed by a cell-permeable analog of cGMP. Treatment with fMLF induced
      phosphorylation of soluble N-ethylmaleimide-sensitive factor-attachment protein
      (SNAP)-23, syntaxins 2, 4, and 6, and Monc18-3. The induced phosphorylation of
      SNAP-23 and syntaxins 2 and 4 was blocked by Rp-8-Br-PET-cGMP and LY294002.
      However, LY294002 was less effective in inhibiting Munc18-3 phosphorylation. The
      induced phosphorylation of syntaxin 6 was not effectively blocked by either Rp-8
      Br-PET-cGMP or LY294002. Treatment of human neutrophils with the PKG inhibitors
      and LY294002 reduced enzyme release from primary, secondary, and tertiary
      granules. These results suggest that PKG and PI3K are involved in degranulation,
      possibly through phosphorylation of target membrane SNAP receptor proteins and
      their binding proteins.

PMID- 17182581
TI  - 3D7-Derived Plasmodium falciparum erythrocyte membrane protein 1 is a frequent
      target of naturally acquired antibodies recognizing protein domains in a
      particular pattern independent of malaria transmission intensity.
AB  - Protection against Plasmodium falciparum malaria is largely mediated by IgG
      against surface Ags such as the erythrocyte membrane protein 1 family (PfEMP1)
      responsible for antigenic variation and sequestration of infected erythrocytes.
      PfEMP1 molecules can be divided into groups A, B/A, B, C, and B/C. We have
      previously suggested that expression of groups A and B/A PfEMP1 is associated
      with severe disease and that Abs to these molecules are acquired earlier in life
      than Abs to PfEMP1 belonging to groups B, B/C, and C PfEMP1. In this study, we
      compared the acquisition of IgG to 20 rPfEMP1 domains derived from 3D7 in
      individuals living under markedly different malaria transmission intensity and
      were unable to find differences in the Ab acquisition rate to PfEMP1 of different
      groupings (A, B, or C) or domain type (alpha, beta, gamma, delta, epsilon, or x).
      Abs were acquired early in life in individuals living in the high transmission
      village and by the age of 2-4 years most individuals had Abs against most
      constructs. This level of reactivity was found at the age of 10-20 years in the
      medium transmission village and was never reached by individuals living under low
      transmission. Nevertheless, the sequence by which individuals acquired Abs to
      particular constructs was largely the same in the three villages. This indicates
      that the pattern of PfEMP1 expression by parasites transmitted at the different
      sites was similar, suggesting that PfEMP1 expression is nonrandom and shaped by
      host-parasite relationship factors operating at all transmission intensities.

PMID- 17182582
TI  - A novel function for galectin-1 at the crossroad of innate and adaptive immunity:
      galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK
      dependent pathway.
AB  - Several environmental factors can differentially regulate monocyte and macrophage
      response patterns, resulting in the display of distinct functional phenotypes.
      Galectin-1, an endogenous lectin found at peripheral lymphoid organs and
      inflammatory sites, has shown immunoregulatory activity in vivo in experimental
      models of autoimmunity and cancer. Whereas compelling evidence has been
      accumulated regarding the effects of galectin-1 on T cell fate, limited
      information is available on how galectin-1 may impact other immune cell types. In
      the present study, we report a novel role for galectin-1 in the regulation of
      monocyte and macrophage physiology. Treatment with galectin-1 in vitro
      differentially regulates constitutive and inducible FcgammaRI expression on human
      monocytes and FcgammaRI-dependent phagocytosis. In addition, galectin-1 inhibits
      IFN-gamma-induced MHC class II (MHC-II) expression and MHC-II-dependent Ag
      presentation in a dose-dependent manner. These regulatory effects were also
      evident in mouse macrophages recruited in response to inflammatory stimuli
      following treatment with recombinant galectin-1 and further confirmed in galectin
      1-deficient mice. Investigation of the mechanisms involved in these functions
      showed that galectin-1 does not affect survival of human monocytes, but rather
      influences FcgammaRI- and MHC-II-dependent functions through active mechanisms
      involving modulation of an ERK1/2-dependent pathway. Our results provide evidence
      of a novel unrecognized role for galectin-1 in the control of monocyte/macrophage
      physiology with potential implications at the crossroad of innate and adaptive
      immunity.

PMID- 17182583
TI  - Opposite regulation of IL-1beta and secreted IL-1 receptor antagonist production
      by phosphatidylinositide-3 kinases in human monocytes activated by
      lipopolysaccharides or contact with T cells.
AB  - The unbalanced production of IL-1beta and its natural, specific inhibitor, the
      secreted IL-1R antagonist (sIL-1Ra), plays an important role in chronic/sterile
      inflammation. Relevant to this condition is direct cellular contact with
      stimulated T cells which is a potent inducer of cytokine production in human
      monocytes/macrophages. We previously demonstrated that activation of PI3Ks is a
      prerequisite of the transcription of the sIL-1Ra gene in human monocytes
      activated by IFN-beta. In this study, we addressed the question of PI3K
      involvement in the production of IL-1beta and sIL-1Ra in monocytes activated by
      cellular contact with stimulated T cells (mimicked by CHAPS-solubilized membranes
      of stimulated T cells (CE(sHUT))), and a crude preparation of LPS, to compare
      stimuli relevant to chronic/sterile and acute/infectious inflammation,
      respectively. In monocytes activated by either CE(sHUT) or LPS, the inhibition of
      PI3Ks abrogated sIL-1Ra transcript expression and sIL-1Ra production,
      demonstrating that PI3Ks control the induction of sIL-1Ra gene transcription. In
      contrast, PI3K inhibition increased the production of IL-1beta protein in both
      CE(sHUT)- and LPS-activated monocytes, the enhancement being drastically higher
      in the former. This was not due to changes in IL-1beta mRNA steady-state levels
      or transcript stability, but to the involvement of PI3Ks in the repression of IL
      1beta secretion. The downstream PI3K effector, Akt, was implicated in this
      process. The present results demonstrate that PI3Ks are involved in the
      inhibition of IL-1beta secretion and in the induction of sIL-1Ra production in
      human blood monocytes by controlling different mechanisms in conditions mimicking
      chronic/sterile (CE(sHUT)) and acute/infectious (LPS) inflammation.

PMID- 17182584
TI  - Dysregulation of Src family kinases in mast cells from epilepsy-resistant ASK
      versus epilepsy-prone EL mice.
AB  - EL mice have been used as a model of epilepsy, whereas ASK mice are an epilepsy
      resistant variant originating from a colony of EL mice. Mast cell-dependent
      anaphylaxis is easily inducible by stimulation with IgE and Ag in ASK mice,
      whereas EL mice are resistant to such stimuli. In this study we have
      characterized mast cells derived from these two strains. ASK mast cells
      proliferated more vigorously than EL cells in response to IL-3 and stem cell
      factor. Although ASK mast cells degranulated less vigorously than EL mast cells
      upon stimulation with IgE and Ag, ASK cells produced and secreted several-fold
      more TNF-alpha and IL-2 than EL cells. Consistent with the similarities of these
      ASK and EL mast cell responses with phenotypes of lyn(-/-) and wild-type mast
      cells, respectively, Lyn activity was reduced in ASK cells. In addition to the
      impaired Lyn activity, ASK cells just like lyn(-/-) cells exhibited reduced Syk
      activity, prolonged activation of ERK and JNK, and enhanced activation of Akt.
      Furthermore, the lipid raft-resident transmembrane adaptor protein Cbp/PAG that
      associates with Lyn was hypophosphorylated in ASK cells. Importantly, similar to
      lyn(-/-) cells, Fyn was hyperactivated in ASK cells. Therefore, these results are
      consistent with the notion that Lyn-dependent phosphorylation of Cbp/PAG
      negatively regulates Src family kinases. This study also suggests that reduced
      activity of Lyn, a negative regulator of mast cell activation, underlies the
      susceptibility of ASK mice to anaphylaxis and implies that dysregulation of Lyn
      and other Src family kinases contributes to epileptogenesis.

PMID- 17182585
TI  - Differential regulation of cytokine release and leukocyte migration by
      lipopolysaccharide-stimulated primary human lung alveolar type II epithelial
      cells and macrophages.
AB  - Bacterial colonization is a secondary feature of many lung disorders associated
      with elevated cytokine levels and increased leukocyte recruitment. We
      hypothesized that, alongside macrophages, the epithelium would be an important
      source of these mediators. We investigated the effect of LPS (0, 10, 100, and
      1000 ng/ml LPS, up to 24 h) on primary human lung macrophages and alveolar type
      II epithelial cells (ATII; isolated from resected lung tissue). Although
      macrophages produced higher levels of the cytokines TNF-alpha and IL-1beta (p <
      0.0001), ATII cells produced higher levels of chemokines MCP-1, IL-8, and growth
      related oncogene alpha (p < 0.001), in a time- and concentration-dependent
      manner. Macrophage (but not ATII cell) responses to LPS required activation of
      ERK1/2 and p38 MAPK signaling cascades; phosphorylated ERK1/2 was constitutively
      up-regulated in ATII cells. Blocking Abs to TNF-alpha and IL-1beta during LPS
      exposure showed that ATII cell (not macrophage) MCP-1 release depended on the
      autocrine effects of IL-1beta and TNF-alpha (p < 0.003, 24 h). ATII cell release
      of IL-6 depended on autocrine effects of TNF-alpha (p < 0.006, 24 h). Macrophage
      IL-6 release was most effectively inhibited when both TNF-alpha and IL-1beta were
      blocked (p < 0.03, 24 h). Conditioned media from ATII cells stimulated more
      leukocyte migration in vitro than conditioned media from macrophages (p <
      0.0002). These results show differential activation of cytokine and chemokine
      release by ATII cells and macrophages following LPS exposure. Activated alveolar
      epithelium is an important source of chemokines that orchestrate leukocyte
      migration to the peripheral lung; early release of TNF-alpha and IL-1beta by
      stimulated macrophages may contribute to alveolar epithelial cell activation and
      chemokine production.

PMID- 17182586
TI  - The net effect of costimulatory blockers is dependent on the subset and
      activation status of the autoreactive T cells.
AB  - In this study, we investigated whether CD4 and CD8 autoreactive T cells have
      different costimulatory requirements for their activation in vitro by testing the
      effect of a panel of Abs specific for various costimulatory molecules. Our
      results showed that CD8 interphotoreceptor retinoid-binding protein-specific T
      cells are more dependent on costimulatory molecules for activation than their CD4
      counterparts. Interphotoreceptor retinoid-binding protein-specific T cells are
      less dependent on costimulatory molecules in the secondary response than the
      primary response. We also showed that blockade of costimulatory molecules can
      either promote or inhibit the proliferation of autoreactive T cells, depending on
      the degree of activation of the cells. Our results show that anti-costimulatory
      molecule treatment can have diverse actions on autoreactive T cell subsets, the
      net effect being determined by the subset of immune cells affected and the type
      and dose of treatment used.

PMID- 17182587
TI  - Critical role of the Fc receptor gamma-chain on APCs in the development of
      allergen-induced airway hyperresponsiveness and inflammation.
AB  - The FcR common gamma-chain (FcRgamma) is an essential component of the receptors
      FcepsilonRI, FcgammaRI, and FcgammaRIII, which are expressed on many inflammatory
      cell types. The role of these receptors in the initiation or maintenance of
      allergic inflammation has not been well defined. FcRgamma-deficient (FcRgamma(-/
      )) and control (wild-type (WT)) mice were sensitized and subsequently challenged
      with OVA. Following sensitization and challenge to OVA, FcRgamma-deficient
      (FcRgamma(-/-)) mice developed comparable levels of IgE and IgG1 as WT mice.
      However, numbers of eosinophils, levels of IL-5, IL-13, and eotaxin in
      bronchoalveolar lavage fluid, and mononuclear cell (MNC) proliferative responses
      to OVA were significantly reduced, as was airway hyperresponsiveness (AHR) to
      inhaled methacholine. Reconstitution of FcRgamma(-/-) mice with whole spleen MNC
      from WT mice before sensitization restored development of AHR and the numbers of
      eosinophils in bronchoalveolar lavage fluid; reconstitution after sensitization
      but before OVA challenge only partially restored these responses. These responses
      were also restored when FcRgamma(-/-) mice received T cell-depleted MNC, T and B
      cell-depleted MNC, or bone marrow-derived dendritic cells before sensitization
      from FcR(+/+) or FcgammaRIII-deficient but not FcRgamma(-/-) mice. The expression
      levels of FcgammaRIV on bone marrow-derived dendritic cells from FcR(+/+) mice
      were found to be low. These results demonstrate that expression of FcRgamma, most
      likely FcgammaRI, on APCs is important during the sensitization phase for the
      development of allergic airway inflammation and AHR.

PMID- 17182588
TI  - TLR3-mediated synthesis and release of eotaxin-1/CCL11 from human bronchial
      smooth muscle cells stimulated with double-stranded RNA.
AB  - Respiratory infections with RNA viruses, such as rhinovirus or respiratory
      syncytial virus, are a major cause of asthma exacerbation, accompanied by
      enhanced neutrophilic and/or eosinophilic inflammation of the airways. We studied
      the effects of dsRNA synthesized during RNA virus replication, and of its
      receptor, TLR3, on the synthesis of eosinophilic chemokines in bronchial smooth
      muscle cells (BSMC). Synthetic dsRNA, polyinosinic-cystidic acid (poly(I:C)),
      induced the synthesis of eosinophilic chemokines, eotaxin-1/CCL11 and
      RANTES/CCL5, from primary cultures of human BSMC, and IL-4 increased
      synergistically the synthesis of poly(I:C)-induced CCL11. A robust eosinophil
      chemotactic activity was released from BSMC stimulated with poly(I:C) and IL-4,
      which was mostly inhibited by preincubation with an anti-CCL11, but not with an
      anti-CCL5 Ab. Although the immunoreactivity of TLR3 was detectable on the
      cellular surface of BSMC by flow cytometric analysis, pretreatment with an anti
      TLR3-neutralizing Ab failed to block the poly(I:C)-induced synthesis of CCL11. We
      have determined by confocal laser-scanning microscopy that the immunoreactivity
      of TLR3 was aggregated intracellularly in poly(I:C)-stimulated BSMC, colocalizing
      with fluorescein-labeled poly(I:C). The synthesis of CCL11 was prominently
      inhibited by the transfection of TLR3-specific small interfering RNA or by
      bafilomycin A1, an endosomal acidification inhibitor, further supporting the
      essential role played by intracellular TLR3 in the synthesis of poly(I:C)-induced
      CCL11 in BSMC. In conclusion, these observations suggest that, by activating
      intracellular TLR3 in BSMC, respiratory RNA virus infections stimulate the
      production of CCL11 and enhance eosinophilic inflammation of the airways in the
      Th2-dominant microenvironment.

PMID- 17182589
TI  - Protectin D1 is generated in asthma and dampens airway inflammation and
      hyperresponsiveness.
AB  - Protectins are newly identified natural chemical mediators that counter leukocyte
      activation to promote resolution of inflammation. In this study, we provide the
      first evidence for protectin D1 (PD1, 10R,17S-dihydroxy-docosa
      4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid) formation from docosahexaenoic acid in
      human asthma in vivo and PD1 counterregulatory actions in allergic airway
      inflammation. PD1 and 17S-hydroxy-docosahexaenoic acid were present in exhaled
      breath condensates from healthy subjects. Of interest, levels of PD1 were
      significantly lower in exhaled breath condensates from subjects with asthma
      exacerbations. PD1 was also present in extracts of murine lungs from both control
      animals and those sensitized and aerosol challenged with allergen. When PD1 was
      administered before aeroallergen challenge, airway eosinophil and T lymphocyte
      recruitment were decreased, as were airway mucus, levels of specific
      proinflammatory mediators, including IL-13, cysteinyl leukotrienes, and PGD(2),
      and airway hyperresponsiveness to inhaled methacholine. Of interest, PD1
      treatment after aeroallergen challenge markedly accelerated the resolution of
      airway inflammation. Together, these findings provide evidence for endogenous PD1
      as a pivotal counterregulatory signal in allergic airway inflammation and point
      to new therapeutic strategies for modulating inflammation in asthmatic lung.

PMID- 17182590
TI  - Hepatitis B virus sensitizes hepatocytes to TRAIL-induced apoptosis through Bax.
AB  - Hepatitis B virus (HBV) infection afflicts >300 million people worldwide and is a
      leading cause of hepatocyte death, cirrhosis, and hepatocellular carcinoma. While
      the morphological characteristics of dying hepatocytes are well documented, the
      molecular mechanisms leading to the death of hepatocytes during HBV infection are
      not well understood. TRAIL, the TNF-related apoptosis-inducing ligand, has
      recently been implicated in the death of hepatocytes under certain inflammatory
      but not normal conditions. To determine the potential roles of TRAIL in HBV
      induced hepatitis, we examined the effects of HBV and its X protein (HBx) on
      TRAIL-induced hepatocyte apoptosis both in vivo and in vitro. We found that
      hepatitis and hepatic cell death in HBV transgenic mice were significantly
      inhibited by a soluble TRAIL receptor that blocks TRAIL function. We also found
      that HBV or HBx transfection of a hepatoma cell line significantly increased its
      sensitivity to TRAIL-induced apoptosis. The increase in TRAIL sensitivity were
      associated with a dramatic up-regulation of Bax protein expression. Knocking down
      Bax expression using Bax-specific small interference RNA blocked HBV-induced
      hepatitis and hepatocyte apoptosis. The degradation of caspases 3 and 9, but not
      that of Bid or caspase-8, was preferentially affected by Bax knockdown. These
      results establish that HBV sensitizes hepatocytes to TRAIL-induced apoptosis
      through Bax and that Bax-specific small interference RNA can be used to inhibit
      HBV-induced hepatic cell death.

PMID- 17182591
TI  - IL-13 is pivotal in the fibro-obliterative process of bronchiolitis obliterans
      syndrome.
AB  - Acute allograft rejection is considered to be a predominately type 1 immune
      mediated response to the donor alloantigen. However, the type 2 immune mediated
      response has been implicated in multiple fibroproliferative diseases. Based on
      the fibro-obliterative lesion found during bronchiolitis obliterans syndrome
      (BOS), we hypothesized that the type 2 immune mediated response is involved in
      chronic lung allograft rejection. Specifically, whereas acute rejection is, in
      part, a type 1 immune response, chronic rejection is, in part, a type 2 immune
      response. We found the type 2 cytokine, IL-13, to be elevated and biologically
      active in human bronchoalveolar lavage fluid during BOS. Translational studies
      using a murine model of BOS demonstrated increased expression of IL-13 and its
      receptors that paralleled fibro-obliteration. In addition, in vivo neutralization
      of IL-13 reduced airway allograft matrix deposition and murine BOS, by a
      mechanism that was independent of IL-4. Furthermore, using IL-13Ralpha2(-/-)
      mice, we found increased fibro-obliteration. Moreover, anti-IL-13 therapy in
      combination with cyclosporin A had profound effects on reducing murine BOS. This
      supports the notion that IL-13 biological axis plays an important role during the
      pathogenesis of BOS independent of the IL-4 biological axis.

PMID- 17182592
TI  - Dendritic cell transmigration through brain microvessel endothelium is regulated
      by MIP-1alpha chemokine and matrix metalloproteinases.
AB  - Dendritic cells (DCs) accumulate in the CNS during inflammatory diseases, but the
      exact mechanism regulating their traffic into the CNS remains to be defined. We
      now report that MIP-1alpha increases the transmigration of bone marrow-derived,
      GFP-labeled DCs across brain microvessel endothelial cell monolayers.
      Furthermore, occludin, an important element of endothelial tight junctions, is
      reorganized when DCs migrate across brain capillary endothelial cell monolayers
      without causing significant changes in the barrier integrity as measured by
      transendothelial electrical resistance. We show that DCs produce matrix
      metalloproteinases (MMP) -2 and -9 and GM6001, an MMP inhibitor, decreases both
      baseline and MIP-1alpha-induced DC transmigration. These observations suggest
      that DC transmigration across brain endothelial cell monolayers is partly MMP
      dependent. The migrated DCs express higher levels of CD40, CD80, and CD86
      costimulatory molecules and induce T cell proliferation, indicating that the
      transmigration of DCs across brain endothelial cell monolayers contributes to the
      maintenance of DC Ag-presenting function. The MMP dependence of DC migration
      across brain endothelial cell monolayers raises the possibility that MMP blockers
      may decrease the initiation of T cell recruitment and neuroinflammation in the
      CNS.

PMID- 17182593
TI  - C-reactive protein-mediated suppression of nephrotoxic nephritis: role of
      macrophages, complement, and Fcgamma receptors.
AB  - C-reactive protein (CRP) is a member of the pentraxin family of proteins and an
      acute phase reactant. CRP modulates the response to inflammatory stimuli
      including LPS and C5a. We recently demonstrated that CRP prevents and reverses
      proteinuria in accelerated nephrotoxic nephritis (NTN). NTN is a model of active
      inflammatory immune complex-mediated nephritis induced by injection of
      antiglomerular basement membrane. CRP treatment prevented the induction of NTN in
      C57BL/6 (B6) mice, increased survival, and reversed ongoing nephritis. Protection
      was associated with a decrease in IL-1beta and chemokines in the kidney and
      peritoneal cells as measured by quantitative RT-PCR. However, IL-10(-/-) mice
      were not protected by CRP either when given before disease onset or when disease
      activity was maximal. FcgammaRI(-/-) mice developed NTN, but were only
      transiently protected by CRP treatment. This transient protection was abrogated
      by cobra venom factor depletion of complement from FcgammaRI(-/-) mice. However,
      complement depletion did not prevent CRP-mediated protection in B6 mice, and CRP
      was protective in C3(-/-) mice. The role of macrophages in the protection
      provided by CRP was tested by treating B6 mice with liposomes containing
      clodronate. Clodronate-containing liposomes deplete mice of splenic and hepatic
      macrophages for 5-7 days. Pretreatment of NTN mice with clodronate but not
      control liposomes completely prevented CRP-mediated protection. These studies
      suggest that CRP mediates protection from NTN through the induction of IL-10 and
      that macrophages are required. In addition, FcgammaRI plays an important role but
      is not the sole mediator of CRP-mediated protection.

PMID- 17182594
TI  - Urinary bladder epithelium antigen induces CD8+ T cell tolerance, activation, and
      autoimmune response.
AB  - The effort to explore the specific autoimmune mechanisms of urinary bladder has
      long been hindered due to a lack of proper animal models. To better elucidate
      this issue, we developed a novel line of transgenic (Tg) mice, designated as URO
      OVA mice, that express the model Ag OVA as a "self"-Ag on the bladder epithelium.
      URO-OVA mice are naturally tolerant to OVA and show no response to OVA
      stimulation. Adoptive transfer of naive OVA-specific T cells showed cell
      proliferation, activation, and infiltration but no bladder histopathology. In
      contrast, adoptive transfer of activated OVA-specific T cells induced OVA
      mediated histological bladder inflammation. Increased mast cells and up-regulated
      mRNA expressions of TNF-alpha, nerve growth factor, and substance P precursor
      were also observed in the inflamed bladder. To further facilitate bladder
      autoimmunity study, we crossbred URO-OVA mice with OVA-specific CD8(+) TCR Tg
      mice (OT-I mice) to generate a dual Tg line URO-OVA/OT-I mice. The latter mice
      naturally acquire clonal deletion for autoreactive OT-I CD8(+) T cells (partial
      deletion in the thymus and severe deletion in the periphery). Despite this clonal
      deletion, URO-OVA/OT-I mice spontaneously develop autoimmune cystitis at 10 wk of
      age. Further studies demonstrated that the inflamed bladder contained
      infiltrating OT-I CD8(+) T cells that had escaped clonal deletion and gained
      effector functions before developing histological bladder inflammation. Taken
      together, we demonstrate for the first time that the bladder epithelium actively
      presents self-Ag to the immune system and induces CD8(+) T cell tolerance,
      activation, and autoimmune response.

PMID- 17182595
TI  - A local antigen-driven humoral response is present in the inflammatory
      myopathies.
AB  - The inflammatory myopathies are putative autoimmune disorders characterized by
      muscle weakness and the presence of intramuscular inflammatory infiltrates.
      Although inclusion body myositis and polymyositis have been characterized as
      cytotoxic CD8(+) T cell-mediated diseases, we recently demonstrated high
      frequencies of CD138(+) plasma cells in the inflamed muscle tissue of patients
      with these diseases. To gain a deeper understanding of the role these B cell
      family members play in the disease pathology, we examined the molecular
      characteristics of the H chain portion of the Ag receptor. Biopsies of muscle
      tissue were sectioned and tissue regions and individual cells were isolated
      through laser capture microdissection. Ig H chain gene transcripts isolated from
      the sections, regions, and cells were used to determine the variable region gene
      sequences. Analysis of these sequences revealed clear evidence of affinity
      maturation in that significant somatic mutation, isotype switching, receptor
      revision, codon insertion/deletion, and oligoclonal expansion had occurred within
      the B and plasma cell populations. Moreover, analysis of tissue regions isolated
      by laser capture microdissection revealed both clonal expansion and variation,
      suggesting that local B cell maturation occurs within muscle. In contrast,
      sequences from control muscle tissues and peripheral blood revealed none of these
      characteristics found in inflammatory myopathy muscle tissue. Collectively, these
      data demonstrate that Ag drives a B cell Ag-specific response in muscle in
      patients with dermatomyositis, inclusion body myositis, and polymyositis. These
      findings highlight the need for a revision of the current paradigm of exclusively
      T cell-mediated intramuscular Ag-specific autoimmunity in inclusion body myositis
      and polymyositis.

PMID- 17182596
TI  - B cell clonal expansion and somatic hypermutation of Ig variable heavy chain
      genes in the synovial membrane of patients with osteoarthritis.
AB  - Inflammatory mediators have been explored as possible factors in the initiation
      and/or progression of osteoarthritis (OA). This study shows that synovial
      infiltration by B lymphocytes is present in almost half of the knee OA cases. The
      degree of B lymphocyte infiltration is associated with more pronounced synovial
      inflammation and with the presence of plasma cells and lymphoid follicles in more
      severe cases. To examine whether these B cells are merely bystanders or could be
      involved in the pathogenesis of OA, we analyzed the Ig H chain variable region
      (V(H)) genes of B cells recovered from the synovial membrane of five OA patients
      with marked B cell infiltration. Sequence analysis of CDR3 regions of rearranged
      VDJ genes revealed clonal or oligoclonal B cell expansions in all cases. Expanded
      B cell clones in four of five OA patients showed clustered somatic mutations,
      occurring mainly in the CDRs and with a high replacement-to-silent ratio (>2.9),
      indicating that these cells are postgerminal center B cells that had been
      positively selected through their Ag receptor. These data demonstrate the
      presence in inflamed knee OA synovium of clonally expanded, Ag-driven B cells
      that may contribute to the development or progression of the disease.

PMID- 17182597
TI  - Elicitation of T cell responses to histologically unrelated tumors by
      immunization with the novel cancer-testis antigen, brother of the regulator of
      imprinted sites.
AB  - Brother of the regulator of imprinted sites (BORIS) was previously described as a
      transcription factor for epigenetic reprogramming the expression of which is
      strictly confined to germ cells of adult testes but is aberrantly activated in
      the vast majority of neoplastic cells. Considering the critical role of BORIS in
      cancerogenesis and the fact that its expression pattern may preclude thymic
      tolerance, we generated DNA- and protein-based mouse BORIS antitumor vaccines
      using a non-DNA-binding version of the BORIS molecule. Clinical use of BORIS as a
      vaccine Ag would require that certain safety concerns be met. Specifically,
      administration of the functional BORIS protein would hypothetically pose a risk
      of BORIS accelerating the progression of cancer. To alleviate such safety
      concerns, we have developed vaccines based on the BORIS molecule lacking the DNA
      binding zinc fingers domain. To enhance anti-BORIS cellular immune responses, we
      used a standard molecular adjuvant approach. It consisted of plasmids encoding
      murine IL-12 and IL-18 for a DNA-based vaccine and conventional Th1 type
      adjuvant, Quil A, for a protein-based vaccine. Both DNA- and protein-based
      vaccines induced Ag-specific CD4(+) T cell proliferation with Th1 and Th2
      cytokine profiles, respectively. Protein-based, but not DNA-based, BORIS vaccine
      induced a significant level of Ab production in immunized animals. Importantly,
      potent anticancer CD8(+)-cytotoxic lymphocytes were generated after immunization
      with the DNA-based, but not protein-based, BORIS vaccine. These cytolytic
      responses were observed across a wide range of different mouse cancers including
      mammary adenocarcinoma, glioma, leukemia, and mastocytoma.

PMID- 17182598
TI  - Prolonged, NK cell-mediated antitumor effects of suicide gene therapy combined
      with monocyte chemoattractant protein-1 against hepatocellular carcinoma.
AB  - Tumor recurrence rates remain high after curative treatments for hepatocellular
      carcinoma (HCC). Immunomodulatory agents, including chemokines, are believed to
      enhance the antitumor effects of tumor cell apoptosis induced by suicide gene
      therapy. We therefore evaluated the immunomodulatory effects of a bicistronic
      recombinant adenovirus vector (rAd) expressing both HSV thymidine kinase and MCP
      1 on HCC cells. Using an athymic nude mouse model (BALB/c-nu/nu), primary s.c.
      tumors (HuH7; human HCC cells) were completely eradicated by rAd followed by
      treatment with ganciclovir. The same animals were subsequently rechallenged with
      HCC cells, tumor development was monitored, and the recruitment or activation of
      NK cells was analyzed immunohistochemically or by measuring IFN-gamma mRNA
      expression. Tumor growth was markedly suppressed as compared with that in mice
      treated with a rAd expressing the HSV thymidine kinase gene alone (p < 0.001).
      Suppression of tumor growth was associated with the elevation of serum IL-12 and
      IL-18. During suppression, NK cells were recruited exclusively, and Th1 cytokine
      gene expression was enhanced in tumor tissues. The antitumor activity, however,
      was abolished either when the NK cells were inactivated with anti-asialo GM1 Ab
      or when anti-IL-12 and anti-IL-18 Abs were administered. These results indicate
      that suicide gene therapy, together with delivery of MCP-1, eradicates HCC cells
      and exerts prolonged NK cell-mediated antitumor effects in a model of HCC,
      suggesting a plausible strategy to prevent tumor recurrence.

PMID- 17182599
TI  - Suppression of skin lesions by transdermal application of CpG
      oligodeoxynucleotides in NC/Nga mice, a model of human atopic dermatitis.
AB  - Atopic dermatitis (AD) is a pruritic inflammatory skin disease characterized by
      an elevation of the total IgE level in plasma, the infiltration of mast cells and
      eosinophils, and the expression of cytokines by Th2 cells. NC/Nga mice kept in
      conventional conditions are known to develop skin lesions resembling human AD. We
      examined in this study the alterations of immune response in NC/Nga mice kept in
      conventional conditions, following transdermal application of CpG
      oligodeoxynucleotides (ODN), which plays a critical role in immunity via the
      augmentation of Th1-type and suppression of Th2-type responses. CpG-ODN
      remarkably changed the immune response from type Th2 to Th1 as determined from
      cytokine mRNA and Ab levels. The serum IgE level was decreased and the expression
      of IgG2a was up-regulated. The application of CpG-ODN to the skin also decreased
      inflammatory infiltration of mast cells, and suppression in the skin lesions was
      observed. Furthermore, the generation of regulatory T cells, which are considered
      immune suppressive T cells, was observed in the skin on treatment with CpG-ODN.
      These results suggested CpG-ODN is effective for immunotherapy in patients with
      AD, which is characterized by Th2-dominated inflammation.

PMID- 17182600
TI  - An inflammatory pathway of IFN-gamma production in coronary atherosclerosis.
AB  - Inflammation is associated with the pathogenesis of coronary atherosclerosis,
      although the mechanisms remain unclear. We investigated whether cytokine
      secretion by innate immune responses could contribute to the production of
      proarteriosclerotic Th1-type cytokines in human coronary atherosclerosis.
      Cytokines were measured by ELISA in the plasma of patients with coronary
      atherosclerosis undergoing cardiac catheterization. IL-18 was detected in all
      subjects, whereas a subset of patients demonstrated a coordinated induction of
      other IFN-gamma-related cytokines. Specifically, elevated plasma levels of IL-12
      correlated with that of IFN-gamma and IFN-gamma-inducible chemokines, defining an
      IFN-gamma axis that was activated independently of IL-6 or C-reactive protein.
      Systemic inflammation triggered by cardiopulmonary bypass increased plasma levels
      of the IFN-gamma axis, but not that of IL-18. Activation of the IFN-gamma axis
      was not associated with acute coronary syndromes, but portended increased
      morbidity and mortality after 1-year follow-up. IL-12 and IL-18, but not other
      monokines, elicited secretion of IFN-gamma and IFN-gamma-inducible chemokines in
      human atherosclerotic coronary arteries maintained in organ culture. T cells were
      the principal source of IFN-gamma in response to IL-12/IL-18 within the arterial
      wall. This inflammatory response did not require, but was synergistic with and
      primed for TCR signals. IL-12/IL-18-stimulated T cells displayed a cytokine
      producing, nonproliferating, and noncytolytic phenotype, consistent with previous
      descriptions of lymphocytes in stable plaques. In contrast to cognate stimuli, IL
      12/IL-18-dependent IFN-gamma secretion was prevented by a p38 MAPK inhibitor and
      not by cyclosporine. In conclusion, circulating IL-12 may provide a mechanistic
      link between inflammation and Th1-type cytokine production in coronary
      atherosclerosis.

PMID- 17182601
TI  - Th1 and type 1 cytotoxic T cells dominate responses in T-bet overexpression
      transgenic mice that develop contact dermatitis.
AB  - Contact dermatitis in humans and contact hypersensitivity (CHS) in animal models
      are delayed-type hypersensitivity reactions mediated by hapten-specific T cells.
      Recently, it has become clear that both CD4(+) Th1 and CD8(+) type 1 cytotoxic T
      (Tc1) cells can act as effectors in CHS reactions. T-bet has been demonstrated to
      play an important role in Th1 and Tc1 cell differentiation, but little is known
      about its contribution to CHS. In the present study, we used C57BL/6 mice
      transgenic (Tg) for T-bet to address this issue. These Tg mice, which
      overexpressed T-bet in their T lymphocytes, developed dermatitis characterized by
      swollen, flaky, and scaly skin in regions without body hair. Skin histology
      showed epidermal hyperkeratosis, neutrophil, and lymphocyte infiltration similar
      to that seen in contact dermatitis. T-bet overexpression in Tg mice led to
      elevated Th1 Ig (IgG2a) and decreased Th2 Ig (IgG1) production. Intracellular
      cytokine analyses demonstrated that IFN-gamma was increased in both Th1 and Tc1
      cells. Furthermore, Tg mice had hypersensitive responses to 2,4
      dinitrofluorobenzene, which is used for CHS induction. These results suggest that
      the level of expression of T-bet might play an important role in the development
      of contact dermatitis and that these Tg mice should be a useful model for contact
      dermatitis.

PMID- 17182602
TI  - Streptococcal preparation OK-432 promotes fusion efficiency and enhances
      induction of antigen-specific CTL by fusions of dendritic cells and colorectal
      cancer cells.
AB  - Dendritic/tumor fusion cell (FC) vaccine is an effective approach for various
      types of cancer but has not yet been standardized. Antitumor activity can be
      modulated by different mechanisms such as dendritic cell (DC) maturation state.
      This study addressed optimal strategies for FC preparations to enhance Ag
      specific CTL activity. We have created three types of FC preparations by
      alternating fusion cell partners: 1) immature DCs fused with autologous
      colorectal carcinoma cells (Imm-FCs); 2) Imm-FCs followed by stimulation with
      penicillin-inactivated Streptococcus pyogenes (OK-432) (Imm-FCs/OK); and 3) OK
      432-stimulated DCs directly fused to autologous colorectal carcinoma cells (OK
      FCs). Both OK-FCs and Imm-FCs/OK coexpressed the CEA, MUC1, and significantly
      higher levels of CD86, CD83, and IL-12 than those obtained with Imm-FCs. Short
      term culture of fusion cell preparations promoted the fusion efficiency.
      Interestingly, OK-FCs were more efficient in stimulating CD4(+) and CD8(+) T
      cells capable of high levels of IFN-gamma production and cytolysis of autologous
      tumor or semiallogeneic targets. Moreover, OK-FCs are more effective inducer of
      CTL activation compared with Imm-FCs/OK on a per fusion cell basis. The
      pentameric assay confirmed that CEA- and MUC1-specific CTL was induced
      simultaneously by OK-FCs at high frequency. Furthermore, the cryopreserved OK-FCs
      retained stimulatory capacity for inducing antitumor immunity. These results
      suggest that OK-432 promotes fusion efficiency and induction of Ag-specific CTL
      by fusion cells. We conclude that DCs fused after stimulation by OK-432 may have
      the potential applicability to the field of antitumor immunotherapy and may
      provide a platform for adoptive immunotherapy in the clinical setting.

PMID- 17182603
TI  - Results of the regional intercomparison exercise for the determination of
      operational quantity HP(10) in Latin America.
AB  - Several intercomparison exercises were organised by the International Atomic
      Energy Agency (IAEA) on the determination of operational quantities at the
      regional or interregional basis. In the Latin American region an intercomparison
      for the determination of the operational quantity Hp(10) was completed mid-2004,
      as a follow-up to previous exercises carried out during the 1990s. Eighteen
      individual external monitoring services from nineteen Member States participated
      in the first phase. The second phase grouped 15 services that had participated in
      the first phase. Dosemeter irradiations in photon beams were done by four
      Secondary Standard Dosimetry Laboratories (SSDLs) of the region. The preparation
      of this exercises involved an audit by the IAEA SSDL, where reference
      irradiations were provided to all participants for verification of their systems.
      During the first phase (2002-2003) only 9 out of 18 services met the performance
      requirements for such monitoring services. Necessary corrective actions and
      procedure verification were implemented. During the second phase (2004) 11 out of
      15 services fulfilled the performance criteria. This intercomparison shows that
      there has been improvement in the second phase and most participants demonstrated
      a satisfactory performance of the quantity tested.

PMID- 17182604
TI  - The sensitivity of the alkaline comet assay in detecting DNA lesions induced by X
      rays, gamma rays and alpha particles.
AB  - Experiments were designed and performed in order to investigate whether or not
      the different cellular energy deposition patterns of photon radiation with
      different energies (29 kV, 220 kV X rays; Co-60, Cs-137-gamma-rays) and alpha
      radiation from an Am-241 source differ in DNA damage induction capacity in human
      cells. For this purpose, the alkaline comet assay (single cell gel
      electrophoresis) was applied to measure the amount of DNA damage in relation to
      the dose received. The comet assay data for the parameters '% DNA in the tail'
      and 'tail moment' for human peripheral lymphocytes did not indicate any
      difference in the initial radiation damage produced by 29 kV X rays relative to
      the reference radiations, 220 kV X rays and the gamma rays, whether for the total
      mean dose range of 0-3 Gy nor in the low-dose range. In contrast, when the 'tail
      length' data were analysed saturation of the fitted dose response curve appeared
      for X rays at about 1.5 Gy but was not apparent for gamma rays up to 3 Gy.
      Preliminary data for alpha exposures of HSC45-M2 cells showed a significant
      increase in DNA damage only at high doses (>2 Gy Am-241), but the damage at 2 Gy
      exceeded the damage induced at 2 Gy by Cs-137-gamma-rays by a factor of 2.5. In
      contrast, other experiments involving different cell systems and DNA damage
      indicators such as chromosomal aberrations have detected a significant increase
      in DNA damage at much lower doses, that is at 0.02 Gy for Am-241 and depicte a
      higher biological effectiveness. These results indicate that differences in
      biological effects arise through downstream processing of complex DNA damage.

PMID- 17182605
TI  - Radiation-induced gamma-H2AX in mammalian cells irradiated with a synchrotron X
      ray microbeam.
AB  - In order to study the radiobiological effects from low dose radiation, a cell
      irradiation system using synchrotron X-ray microbeam has been developed, by which
      cells can be recognised individually and irradiated one by one with the desired
      dose of monochromatic X rays. The minimum beam sizes obtained are 2 microm with
      the focusing optics and 5 microm square with the non-focused beam, and the beam
      size can be changed easily with a high-precision slit in the case of a non
      focused beam. Human fibroblast cells were individually irradiated with this
      system, and immunostained by gamma-H2AX antibody to visualise the DNA damage.
      Most of the fluorescent foci were observed in a localised area in cell nuclei,
      the size of which was almost the same as the beam size.

PMID- 17182606
TI  - Electron track simulation using ETMICRO.
AB  - A new Monte Carlo code ETMICRO (Electron Transport code for MICROdosimetry) is
      now available for tracing the electrons down to 10 eV in liquid water. ETMICRO
      employs much the same frame of track construction as the previous programs except
      that the plasmon excitation is left out of consideration and thus there is no
      delocalisation of energy deposition. The inverse mean free path data and the
      corresponding differential values (DIMFPs) were prepared by adopting the Drude
      model parameters that were derived from a new optical data set for liquid water.
      The potential of electrons causing direct damage on DNA has been estimated as
      functions of the energy of electrons and their distance from DNA in an arbitrary
      direction.

PMID- 17182607
TI  - Optimal design and mathematical model applied to establish bioassay programs.
AB  - Bioassays can be used to estimate the initial intake I for the case of an acute
      intake exposure for an individual worker. To evaluate the effective dose, apart
      from I, we need to know other parameters such as activity median aerodynamic
      diameter (AMAD) or the fraction absorption ( f(1)) in the blood from the GI
      tract, but in an accident situation these parameters are often unknown. The
      bioassay measurement values can be used to estimate by fitting the parameters
      unknown. In this paper, optimal designs for the estimation of the unknown
      parameters are developed. The efficiency of the design will depend on the number
      of samples and the measurement accuracy. The method described applies D
      optimality that maximises the determinant of the Fisher information matrix to
      find the best moments where the bioassay measurements should be taken. It
      requires obtaining the analytical solution of the biokinetic model as a function
      of the parameters to be fitted. The method has been implemented in a computer
      program.

PMID- 17182608
TI  - Reticulon 3 binds the 2C protein of enterovirus 71 and is required for viral
      replication.
AB  - Enterovirus 71 is an enterovirus of the family Picornaviridae. The 2C protein of
      poliovirus, a relative of enterovirus 71, is essential for viral replication. The
      poliovirus 2C protein is associated with host membrane vesicles, which form viral
      replication complexes where viral RNA synthesis takes place. We have now
      identified a host-encoded 2C binding protein called reticulon 3, which we found
      to be associated with the replication complex through direct interaction with the
      enterovirus 71-encoded 2C protein. We observed that the N terminus of the 2C
      protein, which has both RNA- and membrane-binding activity, interacted with
      reticulon 3. This region of interaction was mapped to its reticulon homology
      domain, whereas that of 2C was encoded by the 25th amino acid, isoleucine.
      Reticulon 3 could also interact with the 2C proteins encoded by other
      enteroviruses, such as poliovirus and coxsackievirus A16, implying that it is a
      common factor for such viral replication. Reduced production of reticulon 3 by
      RNA interference markedly reduced the synthesis of enterovirus 71-encoded viral
      proteins and replicative double-stranded RNA, reducing plaque formation and
      apoptosis. Furthermore, reintroduction of nondegradable reticulon 3 into these
      knockdown cells rescued enterovirus 71 infectivity, and viral protein and double
      stranded RNA synthesis. Thus, reticulon 3 is an important component of
      enterovirus 71 replication, through its potential role in modulation of the
      sequential interactions between enterovirus 71 viral RNA and the replication
      complex.

PMID- 17182609
TI  - Two novel ubiquitin-fold modifier 1 (Ufm1)-specific proteases, UfSP1 and UfSP2.
AB  - Ubiquitin-fold modifier 1 (Ufm1) is a recently identified new ubiquitin-like
      protein, whose tertiary structure displays a striking resemblance to ubiquitin.
      Similar to ubiquitin, it has a Gly residue conserved across species at the C
      terminal region with extensions of various amino acid sequences that need to be
      processed in vivo prior to conjugation to target proteins. Here we report the
      isolation, cloning, and characterization of two novel mouse Ufm1-specific
      proteases, named UfSP1 and UfSP2. UfSP1 and UfSP2 are composed of 217 and 461
      amino acids, respectively, and they have no sequence homology with previously
      known proteases. UfSP2 is present in most, if not all, of multicellular organisms
      including plant, nematode, fly, and mammal, whereas UfSP1 could not be found in
      plant and nematode upon data base search. UfSP1 and UfSP2 cleaved the C-terminal
      extension of Ufm1 but not that of ubiquitin or other ubiquitin-like proteins,
      such as SUMO-1 and ISG15. Both were also capable of releasing Ufm1 from Ufm1
      conjugated cellular proteins. They were sensitive to inhibition by sulfhydryl
      blocking agents, such as N-ethylmaleimide, and their active site Cys could be
      labeled with Ufm1-vinylmethylester. Moreover, replacement of the conserved Cys
      residue by Ser resulted in a complete loss of the UfSP1 and UfSP2 activities.
      These results indicate that UfSP1 and UfSP2 are novel thiol proteases that
      specifically process the C terminus of Ufm1.

PMID- 17182610
TI  - Molecular basis of gephyrin clustering at inhibitory synapses: role of G- and E
      domain interactions.
AB  - Gephyrin is a bifunctional modular protein that, in neurons, clusters glycine
      receptors and gamma-aminobutyric acid, type A receptors in the postsynaptic
      membrane of inhibitory synapses. By x-ray crystallography and cross-linking, the
      N-terminal G-domain of gephyrin has been shown to form trimers and the C-terminal
      E-domain dimers, respectively. Gephyrin therefore has been proposed to form a
      hexagonal submembranous lattice onto which inhibitory receptors are anchored.
      Here, crystal structure-based substitutions at oligomerization interfaces
      revealed that both G-domain trimerization and E-domain dimerization are essential
      for the formation of higher order gephyrin oligomers and postsynaptic gephyrin
      clusters. Insertion of the alternatively spliced C5' cassette into the G-domain
      inhibited clustering by interfering with trimerization, and mutation of the
      glycine receptor beta-subunit binding region prevented the localization of the
      clusters at synaptic sites. Together our findings show that domain interactions
      mediate gephyrin scaffold formation.

PMID- 17182611
TI  - Caffeine promotes apoptosis in mitotic spindle checkpoint-arrested cells.
AB  - The spindle assembly checkpoint arrests cells in mitosis when defects in mitotic
      spindle assembly or partitioning of the replicated genome are detected. This
      checkpoint blocks exit from mitosis until the defect is rectified or the cell
      initiates apoptosis. In this study we have used caffeine to identify components
      of the mechanism that signals apoptosis in mitotic checkpoint-arrested cells.
      Addition of caffeine to spindle checkpoint-arrested cells induced >40% apoptosis
      within 5 h. It also caused proteasome-mediated destruction of cyclin B1, a
      corresponding reduction in cyclin B1/cdk1 activity, and reduction in MPM-2
      reactivity. However, cells retained MAD2 staining at the kinetochores, an
      indication of continued spindle checkpoint function. Blocking proteasome activity
      did not block apoptosis, but continued spindle checkpoint function was essential
      for apoptosis. After systematically eliminating all known targets, we have
      identified p21-activated kinase PAK1, which has an anti-apoptotic function in
      spindle checkpoint-arrested cells, as a target for caffeine inhibition. Knockdown
      of PAK1 also increased apoptosis in spindle checkpoint-arrested cells. This study
      demonstrates that the spindle checkpoint not only regulates mitotic exit but
      apoptosis in mitosis through the activity of PAK1.

PMID- 17182612
TI  - A single enzyme catalyzes both platelet-activating factor production and membrane
      biogenesis of inflammatory cells. Cloning and characterization of acetyl-CoA:LYSO
      PAF acetyltransferase.
AB  - Platelet-activating factor (PAF) is a potent proinflammatory lipid mediator
      eliciting a variety of cellular functions. Lipid mediators, including PAF are
      produced from membrane phospholipids by enzymatic cascades. Although a G protein
      coupled PAF receptor and degradation enzymes have been cloned and characterized,
      the PAF biosynthetic enzyme, aceyl-CoA:lyso-PAF acetyltransferase, has not been
      identified. Here, we cloned lyso-PAF acetyltransferase, which is critical in
      stimulus-dependent formation of PAF. The enzyme is a 60-kDa microsomal protein
      with three putative membrane-spanning domains. The enzyme was induced by
      bacterial endotoxin (lipopolysaccharide), which was suppressed by dexamethasone
      treatment. Surprisingly, the enzyme catalyzed not only biosynthesis of PAF from
      lyso-PAF but also incorporation of arachidonoyl-CoA to produce PAF precursor
      membrane glycerophospholipids (lysophosphatidylcholine acyltransferase activity).
      Under resting conditions, the enzyme prefers arachidonoyl-CoA and contributes to
      membrane biogenesis. Upon acute inflammatory stimulation with lipopolysaccharide,
      the activated enzyme utilizes acetyl-CoA more efficiently and produces PAF. Thus,
      our findings provide a novel concept that a single enzyme catalyzes membrane
      biogenesis of inflammatory cells while producing a prophlogistic mediator in
      response to external stimuli.

PMID- 17182613
TI  - Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance
      of mutant huntingtin and alpha-synuclein.
AB  - Trehalose, a disaccharide present in many non-mammalian species, protects cells
      against various environmental stresses. Whereas some of the protective effects
      may be explained by its chemical chaperone properties, its actions are largely
      unknown. Here we report a novel function of trehalose as an mTOR-independent
      autophagy activator. Trehalose-induced autophagy enhanced the clearance of
      autophagy substrates like mutant huntingtin and the A30P and A53T mutants of
      alpha-synuclein, associated with Huntington disease (HD) and Parkinson disease
      (PD), respectively. Furthermore, trehalose and mTOR inhibition by rapamycin
      together exerted an additive effect on the clearance of these aggregate-prone
      proteins because of increased autophagic activity. By inducing autophagy, we
      showed that trehalose also protects cells against subsequent pro-apoptotic
      insults via the mitochondrial pathway. The dual protective properties of
      trehalose (as an inducer of autophagy and chemical chaperone) and the
      combinatorial strategy with rapamycin may be relevant to the treatment of HD and
      related diseases, where the mutant proteins are autophagy substrates.

PMID- 17182614
TI  - Structural basis for formation and hydrolysis of the calcium messenger cyclic ADP
      ribose by human CD38.
AB  - Human CD38 is a multifunctional ectoenzyme responsible for catalyzing the
      conversions from nicotinamide adenine dinucleotide (NAD) to cyclic ADP-ribose
      (cADPR) and from cADPR to ADP-ribose (ADPR). Both cADPR and ADPR are calcium
      messengers that can mobilize intracellular stores and activate influx as well. In
      this study, we determined three crystal structures of the human CD38 enzymatic
      domain complexed with cADPR at 1.5-A resolution, with its analog, cyclic GDP
      ribose (cGDPR) (1.68 A) and with NGD (2.1 A) a substrate analog of NAD. The
      results indicate that the binding of cADPR or cGDPR to the active site induces
      structural rearrangements in the dipeptide Glu(146)-Asp(147) by as much as 2.7 A)
      providing the first direct evidence of a conformational change at the active site
      during catalysis. In addition, Glu(226) is shown to be critical not only in
      catalysis but also in positioning of cADPR at the catalytic site through strong
      hydrogen bonding interactions. Structural details obtained from these complexes
      provide a step-by-step description of the catalytic processes in the synthesis
      and hydrolysis of cADPR.

PMID- 17182615
TI  - Regulation of Schizosaccharomyces pombe Atf1 protein levels by Sty1-mediated
      phosphorylation and heterodimerization with Pcr1.
AB  - The Atf1 transcription factor plays a vital role in the ability of
      Schizosaccharomyces pombe cells to respond to various stress conditions. It
      regulates the expression of many genes in a stress-dependent manner, and its
      function is dependent upon the stress-activated MAPK, Sty1/Spc1. Moreover, Atf1
      is directly phosphorylated by Sty1. Here we have investigated the role of such
      phosphorylation. Atf1 protein accumulates following stress, and this accumulation
      is lost in a strain defective in the Sty1 signaling pathway. In addition,
      accumulation of a mutant Atf1 protein that can no longer be phosphorylated is
      lost. Measurement of the half-life of Atf1 demonstrates that changes in Atf1
      stability are responsible for this accumulation. Atf1 stability is also regulated
      by its heterodimeric partner, Pcr1. Similarly, Pcr1 levels are regulated by Atf1.
      Thus multiple pathways exist that ensure that Atf1 levels are appropriately
      regulated. Phosphorylation of Atf1 is important for cells to mount a robust
      response to H(2)O(2) stress, because the Atf1 phospho-mutant displays sensitivity
      to this stress, and induction of gene expression is lower than that observed in
      wild-type cells. Surprisingly, however, loss of Atf1 phosphorylation does not
      lead to the complete loss of stress-activated expression of Atf1 target genes.
      Accordingly, the Atf1 phospho-mutant does not display the same overall stress
      sensitivities as the atf1 deletion mutant. Taken together, these data suggest
      that Sty1 phosphorylation of Atf1 is not required for activation of Atf1 per se
      but rather for modulating its stability.

PMID- 17182616
TI  - Modulation of DRAK2 autophosphorylation by antigen receptor signaling in primary
      lymphocytes.
AB  - Death-associated protein-related apoptotic kinase-2 (DRAK2), a member of the
      death-associated protein-like family of serine/threonine kinases, is highly
      expressed in lymphoid organs and is a negative regulator of T cell activation. To
      investigate the regulation of DRAK2 activity in primary lymphocytes, we employed
      mass spectrometry to identify sites of autophosphorylation on DRAK2. These
      studies have revealed a key site of autophosphorylation on serine 12. Using a
      phospho-specific antibody to detect Ser(12) phosphorylation, we found that
      autophosphorylation is induced by antigen receptor stimulation in T and B cells.
      In Jurkat T cells, resting B cells and thymocytes, DRAK2 was hypophosphorylated
      on Ser(12) but rapidly phosphorylated with antigen receptor ligation. This
      increase in phosphorylation was dependent on intracellular calcium mobilization,
      because BAPTA-AM blocked DRAK2 kinase activity, whereas the SERCA inhibitor
      thapsigargin promoted Ser(12) phosphorylation. Our results show that DRAK2 kinase
      activity is regulated in a calcium-dependent manner and that Ser(12)
      phosphorylation is necessary for optimal suppression of T cell activation by this
      kinase, suggesting a potential feedback loop may act to modulate the activity of
      this kinase following antigen receptor signaling.

PMID- 17182617
TI  - Nonribosomal synthesis of fengycin on an enzyme complex formed by fengycin
      synthetases.
AB  - Fengycin, a lipopeptidic antibiotic, is synthesized nonribosomally by five
      fengycin synthetases (FenC, FenD, FenE, FenA, and FenB) in Bacillus subtilis F29
      3. This work demonstrates that these fengycin synthetases interlock to form a
      chain, which coils into a 14.5-nm structure. In this chain, fengycin synthetases
      are linked in the order FenC-FenD-FenE-FenA-FenB by interactions between the C
      terminal region of an upstream enzyme and the N-terminal region of its downstream
      partner enzyme, with their amino acid activation modules arranged colinearly with
      the amino acids in fengycin. This work also reveals that fengycin is synthesized
      on this fengycin synthetase chain, explaining how fengycin is synthesized
      efficiently and accurately. The results from this investigation demonstrate that
      forming a peptide synthetase complex is crucial to nonribosomal peptide
      synthesis.

PMID- 17182618
TI  - Inhibition of hypoxia-inducible factor (HIF) hydroxylases by citric acid cycle
      intermediates: possible links between cell metabolism and stabilization of HIF.
AB  - The stability and transcriptional activity of the hypoxia-inducible factors
      (HIFs) are regulated by two oxygen-dependent events that are catalyzed by three
      HIF prolyl 4-hydroxylases (HIF-P4Hs) and one HIF asparaginyl hydroxylase (FIH).
      We have studied possible links between metabolic pathways and HIF hydroxylases by
      analyzing the abilities of citric acid cycle intermediates to inhibit purified
      human HIF-P4Hs and FIH. Fumarate and succinate were identified as in vitro
      inhibitors of all three HIF-P4Hs, fumarate having K(i) values of 50-80 microM and
      succinate 350-460 microM, whereas neither inhibited FIH. Oxaloacetate was an
      additional inhibitor of all three HIF-P4Hs with K(i) values of 400-1000 microM
      and citrate of HIF-P4H-3, citrate being the most effective inhibitor of FIH with
      a K(i) of 110 microM. Culturing of cells with fumarate diethyl or dimethyl ester,
      or a high concentration of monoethyl ester, stabilized HIF-1alpha and increased
      production of vascular endothelial growth factor and erythropoietin. Similar,
      although much smaller, changes were found in cultured fibroblasts from a patient
      with fumarate hydratase (FH) deficiency and upon silencing FH using small
      interfering RNA. No such effects were seen upon culturing of cells with succinate
      diethyl or dimethyl ester. As FIH was not inhibited by fumarate, our data
      indicate that the transcriptional activity of HIF is quite high even when binding
      of the coactivator p300 is prevented. Our data also support recent suggestions
      that the increased fumarate and succinate levels present in the FH and succinate
      dehydrogenase-deficient tumors, respectively, can inhibit the HIF-P4Hs with
      consequent stabilization of HIF-alphas and effects on tumor pathology.

PMID- 17182619
TI  - Structure/function analysis of the interaction of phosphatidylinositol 4,5
      bisphosphate with actin-capping protein: implications for how capping protein
      binds the actin filament.
AB  - The heterodimeric actin-capping protein (CP) can be inhibited by
      polyphosphoinositides, which may be important for actin polymerization at
      membranes in cells. Here, we have identified a conserved set of basic residues on
      the surface of CP that are important for the interaction with
      phosphatidylinositol 4,5-bisphosphate (PIP(2)). Computational docking studies
      predicted the identity of residues involved in this interaction, and functional
      and physical assays with site-directed mutants of CP confirmed the prediction.
      The PIP(2) binding site overlaps with the more important of the two known actin
      binding sites of CP. Correspondingly, we observed that loss of PIP(2) binding
      correlated with loss of actin binding among the mutants. Using TIRF (total
      internal reflection fluorescence) microscopy, we observed that PIP(2) rapidly
      converted capped actin filaments to a growing state, consistent with uncapping.
      Together, these results extend our understanding of how CP binds to the barbed
      end of the actin filament, and they support the idea that CP can "wobble" when
      bound to the barbed end solely by the C-terminal "tentacle" of its beta-subunit.

PMID- 17182620
TI  - Association of CD38 with nonmuscle myosin heavy chain IIA and Lck is essential
      for the internalization and activation of CD38.
AB  - Activation of CD38 in lymphokine-activated killer (LAK) cells involves
      interleukin-8 (IL8)-mediated protein kinase G (PKG) activation and results in an
      increase in the sustained intracellular Ca(2+) concentration ([Ca(2+)](i)), cADP
      ribose, and LAK cell migration. However, direct phosphorylation or activation of
      CD38 by PKG has not been observed in vitro. In this study, we examined the
      molecular mechanism of PKG-mediated activation of CD38. Nonmuscle myosin heavy
      chain IIA (MHCIIA) was identified as a CD38-associated protein upon IL8
      stimulation. The IL8-induced association of MHCIIA with CD38 was dependent on PKG
      mediated phosphorylation of MHCIIA. Supporting these observations, IL8- or cell
      permeable cGMP analog-induced formation of cADP-ribose, increase in [Ca(2+)](i),
      and migration of LAK cells were inhibited by treatment with the MHCIIA inhibitor
      blebbistatin. Binding studies using purified proteins revealed that the
      association of MHCIIA with CD38 occurred through Lck, a tyrosine kinase.
      Moreover, these three molecules co-immunoprecipitated upon IL8 stimulation of LAK
      cells. IL8 treatment of LAK cells resulted in internalization of CD38, which co
      localized with MHCIIA and Lck, and blebbistatin blocked internalization of CD38.
      These findings demonstrate that the association of phospho-MHCIIA with Lck and
      CD38 is a critical step in the internalization and activation of CD38.

PMID- 17182621
TI  - CD40 ligand binds to alpha5beta1 integrin and triggers cell signaling.
AB  - It was originally thought that the critical role of the CD40 ligand (CD40L) in
      normal and inflammatory immune responses was mainly mediated through its
      interaction with the classic receptor, CD40. However, data from CD40L(-/-) and
      CD40(-/-) mice suggest that the CD40L-induced inflammatory immune response
      involves at least one other receptor. This hypothesis is supported by the fact
      that CD40L stabilizes arterial thrombi through an alphaIIbbeta3-dependent
      mechanism. Here we provide evidence that soluble CD40L (sCD40L) binds to cells of
      the undifferentiated human monocytic U937 cell line in a CD40- and alphaIIbbeta3
      independent manner. Binding of sCD40L to U937 cells was inhibited by anti-CD40L
      monoclonal antibody 5C8, anti-alpha5beta1 monoclonal antibody P1D6, and soluble
      alpha5beta1. The direct binding of sCD40L to purified alpha5beta1 was confirmed
      in a solid phase binding assay. Binding of sCD40L to alpha5beta1 was modulated by
      the form of alpha5beta1 expressed on the cell surface as the activation of
      alpha5beta1 by Mn(2+) or dithiothreitol resulted in the loss of sCD40L binding.
      Moreover, sCD40L induced the translocation of alpha5beta1 to the Triton X-100
      insoluble fraction of U937 cells, the rapid activation of the MAPK pathways
      ERK1/2, and interleukin-8 gene expression. The binding of sCD40L to CD40 on BJAB
      cells, an alpha5beta1-negative B cell line, and the resulting activation of
      ERK1/2 was not inhibited by soluble alpha5beta1, suggesting that sCD40L can bind
      concomitantly to both receptors. These results document the existence of novel
      CD40L-dependent pathways of physiological relevance for cells expressing multiple
      receptors (CD40, alpha5beta1, and alphaIIbbeta3) for CD40L.

PMID- 17182622
TI  - Kallikrein 8 is involved in skin desquamation in cooperation with other
      kallikreins.
AB  - Kallikrein type serine proteases, KLK8/neuropsin, KLK6, and KLK7, have been
      implicated in the proliferation and differentiation of epidermal keratinocytes
      and in the pathogenesis of psoriasis. However, their mechanistic roles in these
      processes remain largely unknown. We applied 12-O-tetradecanoylphorbol-13-acetate
      on the wild type (WT) and the Klk8 gene-disrupted (Klk8(-/-)) mouse skin,
      inducing keratinocyte proliferation similar to the human psoriatic lesion. Klk8
      mRNA as well as Klk6 and Klk7 mRNA were up-regulated after 12-O
      tetradecanoylphorbol-13-acetate application in the WT mice. In contrast, Klk8(-/
      ) mice showed minimum increases of Klk6 and Klk7 transcripts, the proteins, and
      enzymatic activities. Relative to the WT, the Klk8(-/-) skin showed less
      proliferation and an increase in the number of cell layers in the stratum
      corneum. However, overexpression of Klk8 by adenovirus vector in knock-out
      keratinocytes did not result in an increase in Klk6 or Klk7 mRNA. The inefficient
      cleavage of adhesion molecules DSG1 and CDSN in Klk8(-/-) skin contributes to a
      delay in corneocyte shedding, resulting in the hyperkeratosis phenotype. We
      propose that in psoriatic lesion, KLK8 modulates hyperproliferation and prevents
      excessive hyperkeratosis by shedding the corneocytes.

PMID- 17182623
TI  - dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by
      modulating gene expression of pro-inflammatory cytokines and immune response
      related factors.
AB  - dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth
      factor-like homeotic protein family whose expression is known to modulate the
      differentiation signals of mesenchymal and hematopoietic stem cells in bone
      marrow. We have demonstrated previously that Dlk1 can maintain the human bone
      marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify
      the molecular mechanisms underlying these effects, we compared the basal gene
      expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control
      hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In
      response to Dlk1 expression, 128 genes were significantly up-regulated (with >2
      fold; p < 0.001), and 24% of these genes were annotated as immune response
      related factors, including pro-inflammatory cytokines, in addition to factors
      involved in the complement system, apoptosis, and cell adhesion. Also, addition
      of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner.
      As biological consequences of up-regulating these immune response-related
      factors, we showed that the inhibitory effects of dlk1 on osteoblast and
      adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine
      expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the
      immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC,
      and led to marked transactivation of the NF-kappaB. Our data suggest a new role
      for Dlk1 in regulating the multiple biological functions of hMSC by influencing
      the composition of their microenvironment "niche." Our findings also demonstrate
      a role for Dlk1 in mediating the immune response.

PMID- 17182624
TI  - Is there a similarity between DNA damage in adults with chronic alcoholism and
      community-dwelling healthy older adults?
AB  - AIMS: Daily alcohol consumption and ageing have been linked with DNA damage,
      leading to the hypothesis that chronic alcoholism causes DNA damage similar to
      that which occurs with ageing. Likewise, it has been suggested that chronic
      alcoholism is the cause of accelerated or premature ageing. The objective of this
      study was to evaluate the frequency and magnitude of DNA damage among adults with
      chronic alcoholism and healthy older adults residing in Mexico City. METHODS: A
      cross-sectional and comparative study was carried out in a sample of 53 chronic
      alcoholics of 25-44 years of age (without alcohol ingestion in the past 30 days)
      without additional diseases, 26 healthy subjects >or=60 years of age, and 25
      healthy adults of 25-44 years of age without alcohol addiction, all residents of
      Mexico City during the past 10 years. DNA damage was evaluated by single-cell gel
      electrophoresis technique (Comet assay). RESULTS: Our results showed a similar
      percentage of DNA damage between healthy elderly subjects and chronic alcoholics
      (62 vs 55%, P >0.05), although average DNA migration was greater in alcoholics
      than in the elderly (78.1 +/- 33.2 vs 58.6 +/- 26.2, P = 0.09). However, the
      percentage of subjects with more than six damaged cells was higher in the older
      adults subjects group than in the group chronic alcoholics (19 vs 35%, P = 0.16).
      CONCLUSIONS: Data suggest that DNA damage is not similar in young subjects with
      chronic alcoholism that which occurs with ageing.

PMID- 17182625
TI  - Constructing public and political discourse on alcohol issues: towards a
      framework for analysis.
AB  - AIMS: To examine the possibilities for research into news reporting and its role
      in reflecting and informing public and political beliefs and action in relation
      to alcohol and drinking practices. METHOD: Studies on media and alcohol, focusing
      on the role of media in relation to alcohol consumption and drinking-related
      practices, policies and beliefs. RESULTS: Most research on alcohol and media has
      focused on either advertising or entertainment media content, rather than on news
      reporting and its wider social implications. CONCLUSION: The role of news
      reporting could usefully be widened. We offer a framework for analysing the role
      of news media in relation to public debate and practice with regard to alcohol
      and drinking.

PMID- 17182626
TI  - The Stanford Microarray Database: implementation of new analysis tools and open
      source release of software.
AB  - The Stanford Microarray Database (SMD; http://smd.stanford.edu/) is a research
      tool and archive that allows hundreds of researchers worldwide to store,
      annotate, analyze and share data generated by microarray technology. SMD supports
      most major microarray platforms, and is MIAME-supportive and can export or import
      MAGE-ML. The primary mission of SMD is to be a research tool that supports
      researchers from the point of data generation to data publication and
      dissemination, but it also provides unrestricted access to analysis tools and
      public data from 300 publications. In addition to supporting ongoing research,
      SMD makes its source code fully and freely available to others under an Open
      Source license, enabling other groups to create a local installation of SMD. In
      this article, we describe several data analysis tools implemented in SMD and we
      discuss features of our software release.

PMID- 17182627
TI  - Relationships between the physicochemical properties of an amphiphilic triblock
      copolymers/DNA complexes and their intramuscular transfection efficiency.
AB  - Poly(ethyleneoxide)-poly(propyleneoxide)-poly(ethyleneoxide) triblock copolymer
      (PEO-PPO-PEO) based plasmid delivery systems are increasingly drawing attention
      in the field of nonviral gene transfer because of their proven in vivo
      transfection capability. They result from the simple association of DNA molecules
      with uncharged polymers. We examined the physicochemical properties of PEO-PPO
      PEO/DNA mixtures, in which the PEO-PPO-PEO is Lutrol (PEO75-PPO30-PEO75),
      formulated under various conditions. We found that interactions between PEO-PPO
      PEO and DNA are mediated by the central hydrophobic block within the block
      copolymer. Dynamic light scattering and cryo-electron microscopy showed that the
      mean diameter of transfecting particles as well as their stability depended on
      the PEO-PPO-PEO/DNA ratio and on the ionic composition of the formulating medium.
      The most active formulation promoting a good tissue-distribution and an optimal
      transfection was characterized by a reduced electrophoretic mobility, a mean
      hydrodynamic diameter of approximately 250-300 nm and by a conserved B-DNA form
      as shown by circular dichroism studies. Our study also revealed that the
      stability of these formulations strongly depended on a concentration balance
      between the DNA and the PEO-PPO-PEO, over which the DNA conformation was
      modified, micron-sized particles were generated, and the transgene expression was
      declined. We showed that the physicochemical properties of PEO-PPO-PEO/DNA
      formulations directly impact the level of gene expression in transfected muscles.

PMID- 17182628
TI  - The 32 kDa subunit of replication protein A (RPA) participates in the DNA
      replication of Mung bean yellow mosaic India virus (MYMIV) by interacting with
      the viral Rep protein.
AB  - Mung bean yellow mosaic India virus (MYMIV) is a member of genus begomoviridae
      and its genome comprises of bipartite (two components, namely DNA-A and DNA-B),
      single-stranded, circular DNA of about 2.7 kb. During rolling circle replication
      (RCR) of the DNA, the stability of the genome and maintenance of the stem-loop
      structure of the replication origin is crucial. Hence the role of host single
      stranded DNA-binding protein, Replication protein A (RPA), in the RCR of MYMIV
      was examined. Two RPA subunits, namely the RPA70 kDa and RPA32 kDa, were isolated
      from pea and their roles were validated in a yeast system in which MYMIV DNA
      replication has been modelled. Here, we present evidences that only the RPA32 kDa
      subunit directly interacted with the carboxy terminus of MYMIV-Rep both in vitro
      as well as in yeast two-hybrid system. RPA32 modulated the functions of Rep by
      enhancing its ATPase and down regulating its nicking and closing activities. The
      possible role of these modulations in the context of viral DNA replication has
      been discussed. Finally, we showed the positive involvement of RPA32 in transient
      replication of the plasmid DNA bearing MYMIV replication origin using an in
      planta based assay.

PMID- 17182629
TI  - Specific targeting of cytosine methylation to DNA sequences in vivo.
AB  - Development of methods that will allow exogenous imposition of inheritable gene
      specific methylation patterns has potential application in both therapeutics and
      in basic research. An ongoing approach is the use of targeted DNA
      methyltransferases, which consist of a fusion between gene-targeted zinc-finger
      proteins and prokaryotic DNA cytosine methyltransferases. These enzymes however
      have so far demonstrated significant and unacceptable levels of non-targeted
      methylation. We now report the development of second-generation targeted
      methyltransferase enzymes comprising enhanced zinc-finger arrays coupled to
      methyltransferase mutants that are functionally dominated by their zinc-finger
      component. Both in vitro plasmid methylation studies and a novel bacterial assay
      reveal a high degree of target-specific methylation by these enzymes.
      Furthermore, we demonstrate for the first time transient expression of targeted
      cytosine methyltransferase in mammalian cells resulting in the specific
      methylation of a chromosomal locus. Importantly, the resultant methylation
      pattern is inherited through successive cell divisions.

PMID- 17182630
TI  - A novel E4BP4 element drives circadian expression of mPeriod2.
AB  - Period2 (Per2) is an essential component of the mammalian clock mechanism and
      robust circadian expression of Per2 is essential for the maintenance of circadian
      rhythms. Although recent studies have shown that the circadian E2 enhancer (a non
      canonical E-box) accounts for most of the circadian transcriptional drive of
      mPer2, little is known about the other cis-elements of mPer2 oscillatory
      transcription. Here, we examined the contribution of E4BP4 to Per2 mRNA
      oscillation in the cell-autonomous clock. Knockdown experiments of E4BP4 in both
      Northern blots and real-time luciferase assays suggested that endogenous E4BP4
      negatively regulates Per2 mRNA oscillation. Sequence analysis revealed two
      putative E4BP4-binding sites (termed A-site and B-site) on mammalian Per2
      promoter regions. Luciferase assays with mutant constructs showed that a novel
      E4BP4-binding site (B-site) is responsible for E4BP4-mediated transcriptional
      repression of Per2. Furthermore, chromatin immunoprecipitation assays in vivo
      showed that the peak of E4BP4 binding to the B-site on the Per2 promoter almost
      matched the trough of Per2 mRNA expression. Importantly, real-time luciferase
      assays showed that the B-site in addition to the E2 enhancer is required for
      robust circadian expression of Per2 in the cell-autonomous clock. These findings
      indicated that E4BP4 is required for the negative regulation of mammalian
      circadian clocks.

PMID- 17182631
TI  - Spermidine biases the resolution of Holliday junctions by phage lambda integrase.
AB  - Holliday junctions are a central intermediate in diverse pathways of DNA repair
      and recombination. The isomerization of a junction determines the directionality
      of the recombination event. Previous studies have shown that the identity of the
      central sequence of the junction may favor one of the two isomers, in turn
      controlling the direction of the pathway. Here we demonstrate that, in the
      absence of DNA sequence-mediated isomer preference, polycations are the major
      contributor to biasing strand cleavage during junction resolution. In the case of
      wild-type phage lambda excision junctions, spermidine plays the dominant role in
      controlling the isomerization state of the junction and increases the rate of
      junction resolution. Spermidine also counteracts the sequence-imposed bias on
      resolution. The spermidine-induced bias is seen equally on supercoiled and linear
      excisive recombination junction intermediates, and thus is not just an artefact
      of in vitro recombination conditions. The contribution of spermidine requires the
      presence of accessory factors, and results in the repositioning of Int's core
      binding domains on junctions, perhaps due to DNA-spermidine-protein interactions,
      or by influencing DNA conformation in the core region. Our results lead us to
      propose that spermidine together with accessory factors promotes the formation of
      the second junction isomer. We propose that this rearrangement triggers the
      activation of the second pair of Int active sites necessary to resolve Holliday
      junctions during phage lambda Int-mediated recombination.

PMID- 17182632
TI  - Antisense oligonucleotides containing locked nucleic acid improve potency but
      cause significant hepatotoxicity in animals.
AB  - A series of antisense oligonucleotides (ASOs) containing either 2'-O
      methoxyethylribose (MOE) or locked nucleic acid (LNA) modifications were designed
      to investigate whether LNA antisense oligonucleotides (ASOs) have the potential
      to improve upon MOE based ASO therapeutics. Some, but not all, LNA containing
      oligonucleotides increased potency for reducing target mRNA in mouse liver up to
      5-fold relative to the corresponding MOE containing ASOs. However, they also
      showed profound hepatotoxicity as measured by serum transaminases, organ weights
      and body weights. This toxicity was evident for multiple sequences targeting
      three different biological targets, as well as in mismatch control sequences
      having no known mRNA targets. Histopathological evaluation of tissues from LNA
      treated animals confirmed the hepatocellular involvement. Toxicity was observed
      as early as 4 days after a single administration. In contrast, the corresponding
      MOE ASOs showed no evidence for toxicity while maintaining the ability to reduce
      target mRNA. These studies suggest that while LNA ASOs have the potential to
      improve potency, they impose a significant risk of hepatotoxicity.

PMID- 17182633
TI  - Dynamic use of multiple parameter sets in sequence alignment.
AB  - The level of conservation between two homologous sequences often varies among
      sequence regions; functionally important domains are more conserved than the
      remaining regions. Thus, multiple parameter sets should be used in alignment of
      homologous sequences with a stringent parameter set for highly conserved regions
      and a moderate parameter set for weakly conserved regions. We describe an
      alignment algorithm to allow dynamic use of multiple parameter sets with
      different levels of stringency in computation of an optimal alignment of two
      sequences. The algorithm dynamically considers various candidate alignments,
      partitions each candidate alignment into sections, and determines the most
      appropriate set of parameter values for each section of the alignment. The
      algorithm and its local alignment version are implemented in a computer program
      named GAP4. The local alignment algorithm in GAP4, that in its predecessor GAP3,
      and an ordinary local alignment program SIM were evaluated on 257,716 pairs of
      homologous sequences from 100 protein families. On 168,475 of the 257,716 pairs
      (a rate of 65.4%), alignments from GAP4 were more statistically significant than
      alignments from GAP3 and SIM.

PMID- 17182634
TI  - Are socially disadvantaged neighbourhoods deprived of health-related community
      resources?
AB  - BACKGROUND: Recent work in a number of countries has identified growing
      geographical inequalities in health between deprived and non-deprived
      neighbourhoods. The health gaps observed cannot be entirely explained by
      differences in the characteristics of individuals living in those neighbourhoods,
      which has led to a concerted international public health research effort to
      determine what contextual features of neighbourhoods matter. This article reports
      on access to potentially health-promoting community resources across all
      neighbourhoods in New Zealand. Prevailing international opinion is that access to
      community resources is worse in deprived neighbourhoods. METHODS: Geographical
      Information Systems were used to calculate geographical access to 16 types of
      community resources (including recreational amenities, and shopping, educational
      and health facilities) in 38,350 small census areas across the country. The
      distribution of these access measures by neighbourhood socioeconomic deprivation
      was determined. RESULTS: For 15 out of 16 measures of community resources, access
      was clearly better in more deprived neighbourhoods. For example, the travel time
      to large supermarkets was approximately 80% greater in the least deprived
      quintile of neighbourhoods compared with the most deprived quintile. CONCLUSIONS:
      These results challenge the widely held, but largely untested, view that areas of
      high social disadvantage have poorer access to community resources. Poor
      locational access to community resources among deprived neighbourhoods in New
      Zealand does not appear to be an explanation of poorer health in these
      neighbourhoods. If anything, a pro-equity distribution of community resources may
      be preventing even wider disparities in neighbourhood inequalities in health.

PMID- 17182635
TI  - Epidemiologic transition interrupted: a reassessment of mortality trends in
      Thailand, 1980-2000.
AB  - BACKGROUND: In the late 1980s and early 1990s a generalized HIV epidemic affected
      Thailand which was relatively well controlled by an intensive national campaign
      by the mid 1990s. The extent to which the epidemic has slowed or possibly
      reversed the epidemiological transition in Thailand is relatively unknown.
      METHODS: Under-five mortality rates (U5MR) were determined from various sources
      and weighted least squares regression conducted to determine U5MR over the years
      1980-2000. Direct and indirect estimates of the completeness of death
      registration were used to estimate mortality levels in those aged more than 5
      years for the 1980-90 and 1990-2000 periods. Life tables were constructed using
      the various estimates to determine changes in life-expectancy between the two
      time periods. RESULTS: U5MR in Thailand is estimated to have been 58/1000 live
      births in 1980, declining to 30 in 1990 and to 23 in 2000. The vital registration
      system clearly underestimates U5MR. Successive surveys of Population Change (SPC)
      imply coverage of death registration improving from 75-77% in 1985-86 to 95% in
      1995-96, partly due to a reliance on self-reported registration in the latter
      survey. In contrast, the General Growth Balance-Synthetic Extinction Generations
      (GGB-SEG) method suggests coverage worsening from 78-85% in 1980-90 to 64-72% in
      1990-2000. Life tables based on SPC adjustments show continued declines in
      female, and to a lesser extent, male adult mortality with corresponding increases
      in life-expectancy at birth of around 6 years for both sexes from 1980-90 to 1990
      2000. In contrast, the indirect adjustments suggest a substantial increase in
      male adult mortality with female adult mortality unchanged; life expectancy
      decreased by 4 years for males and was only marginally higher in females.
      CONCLUSION: Given the conflicting evidence a definitive assessment of mortality
      change in Thailand between 1980 and 2000 is difficult to make. Indirect
      adjustments, based on demographic methods point to a major reversal in mortality
      decline among males, and a slowing in females. If adult mortality registration
      has declined, and given the continued under-registration of infant and child
      deaths, remedial measures are urgently required if the mortality system is to
      better inform and monitor health development in Thailand.

PMID- 17182636
TI  - On the synthesis and interpretation of consistent but weak gene-disease
      associations in the era of genome-wide association studies.
AB  - Emerging technologies are allowing researchers to study hundreds of thousands of
      genetic variants simultaneously as risk factors for common complex diseases. Both
      theoretical considerations and empirical evidence suggest that specific genetic
      variants causally associated with common diseases will have small effects (risk
      ratios mostly <2.0). However, the combination of even a few small effects (e.g.
      effects of fewer than 20 common genetic variants) could account for a sizeable
      population attributable fraction of common diseases and shed important light on
      disease pathogenesis and environmental determinants. Nevertheless, the
      inauguration of genome-wide association studies only magnifies the challenge of
      differentiating between the expected, true weak associations from the numerous
      spurious effects caused by misclassification, confounding and significance
      chasing biases. Standards are urgently needed for presenting and interpreting
      cumulative evidence on gene-disease associations, especially for consistent but
      weak associations. Criteria for synthesis of the evidence should include sound
      methods for study conduct and analysis, biological plausibility, experimental
      evidence and adequate replication in large-scale, collaborative studies. Efforts
      by the Human Genome Epidemiology Network (HuGENet) are currently ongoing to
      streamline and operationalize these criteria for data on genetic associations
      with common diseases.

PMID- 17182637
TI  - Association of allergic rhinitis with pesticide use among grape farmers in Crete,
      Greece.
AB  - OBJECTIVE: To explore the association of allergic rhinitis with the use of
      pesticides among grape farmers in Crete. METHODS: A cross-sectional study of 120
      grape farmers and 100 controls at the Malevisi region in Northern Crete was
      conducted. The protocol consisted of a questionnaire, skin prick tests for 16
      common allergens, measurement of specific IgE antibodies against 8 allergens, and
      spirometry before and after bronchodilatation. RESULTS: Grape farmers who used
      pesticides had higher prevalence rates of allergic rhinitis symptoms (OR, 3.0;
      95% CI, 1.4 to 6.2) compared with grape farmers who reported no current use of
      pesticides, and control subjects. Logistic regression models controlling for age,
      sex and smoking status showed that 6 of the 12 predefined groups of major
      pesticides were significantly related to allergic rhinitis symptoms. The highest
      risks were observed for paraquat and other bipyridyl herbicides (OR, 2.2; 95% CI,
      1.0 to 4.8), dithiocarbamate fungicides (OR, 2.5; 95% CI, 1.1 to 5.3) and
      carbamate insecticides (OR, 3.0; 95% CI, 1.4 to 6.5). A factor analysis of
      pesticides used identified 3 distinct factors. The most common factor was that of
      multiple pesticide use that included 9 pesticides and was significantly
      associated with allergic rhinitis (OR, 1.5; 95% CI, 1.0 to 2.3). ORs were higher
      when allergic rhinitis was defined using both questionnaire data on symptoms and
      atopy. CONCLUSIONS: Occupational exposure to multiple agricultural chemicals
      could be related to allergic rhinitis in grape farmers.

PMID- 17182638
TI  - Causes of death among lead smelters in relation to the glucose-6-phosphate
      dehydrogenase polymorphism.
AB  - OBJECTIVE: To assess, by updating a follow-up mortality study of a lead smelters
      cohort in Sardinia, Italy, the adverse health effects following occupational lead
      exposure in relation to the glucose-6-phosphate dehydrogenase (G6PD)
      polymorphism. METHOD: The 1973-2003 mortality of 1017 male lead smelters were
      followed-up, divided into two subcohorts according to the G6PD phenotype: whether
      G6PD deficient (G6PD-) or wild-type (wtG6PD). Deaths observed in the overall
      cohort and the two subcohorts were compared with those expected, on the basis of
      the age-, sex- and calendar year-specific mortality in the general male
      population of the island. Directly standardised mortality rates (sr) in the two
      subcohorts were also compared. RESULTS: Cardiovascular mortality was strongly
      reduced among production and maintenance workers, which is most related to the
      healthy worker effect. However, the sr for cardiovascular diseases was
      substantially lower among the G6PD- subcohort (5.0x10(-4)) than among the wtG6PD
      subcohort (33.6x10(-4); chi2 = 1.10; p = NS). Neoplasms of the haemopoietic
      system exceeded the expectation in the G6PD- subcohort (SMR = 388; 95% CI 111 to
      1108). No other cancer sites showed any excess in the overall cohort or in the
      two subcohorts. No death from haemolytic anaemia occurred in the G6PD- subcohort.
      CONCLUSION: With due consideration of the limited statistical power of our study,
      previous results suggesting that in workplaces where exposure is under careful
      control, expressing the G6PD- phenotype does not convey increased susceptibility
      to lead toxicity are confirmed. The observed excess risk of haematopoietic
      malignancies seems to have most likely resulted from chance.

PMID- 17182639
TI  - Air pollution and inflammation in type 2 diabetes: a mechanism for
      susceptibility.
AB  - BACKGROUND: Particulate air pollution has been associated with several adverse
      cardiovascular health outcomes, and people with diabetes may be especially
      vulnerable. One potential pathway is inflammation and endothelial dysfunction
      processes in which cell adhesion molecules and inflammatory markers play
      important roles. AIM: To examine whether plasma levels of soluble intercellular
      adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and von
      Willebrand factor (vWF) were associated with particle exposure in 92 Boston area
      residents with type 2 diabetes. METHODS: Daily average ambient levels of air
      pollution (fine particles (PM2.5), black carbon (BC) and sulphates) were measured
      approximately 500 m from the patient examination site and evaluated for
      associations with ICAM-1, VCAM-1 and vWF. Linear regressions were fit to plasma
      levels of ICAM-1, VCAM-1 and vWF, with the particulate pollutant index, apparent
      temperature, season, age, race, sex, glycosylated haemoglobin, cholesterol,
      smoking history and body mass index as predictors. RESULTS: Air pollutant
      exposure measures showed consistently positive point estimates of association
      with the inflammatory markers. Among participants not taking statins and those
      with a history of smoking, associations between PM(2.5), BC and VCAM-1 were
      particularly strong. CONCLUSIONS: These results corroborate evidence suggesting
      that inflammatory mechanisms may explain the increased risk of air pollution
      associated cardiovascular events among those with diabetes.

PMID- 17182640
TI  - Influenza immunisation: attitudes and beliefs of UK healthcare workers.
AB  - AIM: To explore attitudes to influenza immunisation and rates of uptake among
      staff working in acute hospitals in the UK. METHOD: A cross-sectional survey of
      11,670 healthcare workers in six UK hospitals was carried out using a postal
      questionnaire. RESULTS: Among 6302 responders (54% of those mailed), 19% had
      taken up influenza immunisation during winter 2002/3. Vaccination was well
      tolerated, with a low prevalence of side effects (13%) and associated time off
      work (2%). The majority of subjects who accepted vaccination (66%) were most
      strongly influenced by the personal benefits of protection against influenza.
      Prevention of sickness absence and protection of patients were the prime
      motivation for only 10% and 7% of subjects, respectively. Among 3967 who declined
      vaccination, the most common primary demotivators were concern about safety (31%)
      and efficacy (29%). 22% were most strongly deterred by lack of time to attend for
      vaccination. Free text answers indicated that 37% declined because of a perceived
      low ratio of personal benefits to adverse effects. Subjects said they would be
      persuaded to take up vaccination in future by easier access (36%), more
      information about personal benefit and risk (34%) and more information about
      effects on staff absence (24%). CONCLUSIONS: These findings indicate that the
      uptake of influenza immunisation among UK healthcare workers remains low. There
      is some scope for increasing uptake by improving accessibility and encouragement
      from professional peers. However, the results suggest that perception of small
      personal benefit in relation to risk mitigates, importantly, against higher
      uptake of routine annual influenza vaccination. Thus, resource might better be
      allocated to ensuring efficient management in epidemic years. The effect of
      publicity about pandemic influenza on risk perception and vaccine uptake among
      healthcare workers during winter 2005/6 warrants further study.

PMID- 17182641
TI  - The validation of work-related self-reported asthma exacerbation.
AB  - OBJECTIVE: To determine the validity of work-related self-reported exacerbation
      of asthma using the findings from serial peak expiratory flow (PEF) measurements
      as the standard. METHODS: Adults with asthma treated in a health maintenance
      organisation were asked to conduct serial spirometry testing at home and at work
      for 3 weeks. Self-reported respiratory symptoms and medication use were recorded
      in two ways: a daily log completed concurrently with the serial PEF testing and a
      telephone questionnaire administered after the PEF testing. Three researchers
      evaluated the serial PEF records and judged whether a work relationship was
      evident. RESULTS: 95 of 382 (25%) working adults with asthma provided adequate
      serial PEF data, and 13 of 95 (14%) were judged to have workplace exacerbation of
      asthma (WEA) based on these data. Self-reported concurrent medication use was the
      most valid single operational definition, with a sensitivity of 62% and a
      specificity of 65%. CONCLUSIONS: A work-related pattern of self-reported asthma
      symptoms or medication use was usually not corroborated by serial PEF testing and
      failed to identify many people who had evidence of WEA based on the serial PEF
      measurements.

PMID- 17182642
TI  - Pesticides and other agricultural factors associated with self-reported farmer's
      lung among farm residents in the Agricultural Health Study.
AB  - BACKGROUND: Farmer's lung, or hypersensitivity pneumonitis, is an important
      contributor to respiratory morbidity among farmers. METHODS: Using the 1993-7
      enrolment data from the Agricultural Health Study, we conducted a cross-sectional
      study of occupational risk factors for farmer's lung among 50,000 farmers and
      farm spouses in Iowa and North Carolina using hierarchical logistic regression
      controlling for age, state, and smoking status. Participants provided information
      on agricultural exposures, demographic characteristics, and medical history via
      self-administered questionnaires. Approximately 2% of farmers (n = 481) and 0.2%
      of spouses (n = 51) reported doctor-diagnosed farmer's lung during their
      lifetime. We assessed farmers and spouses separately due to different information
      on occupational exposure history. Only pesticide exposures represented lifetime
      exposure history, all other farm exposures represented current activities at
      enrolment. RESULTS: Among farmers, handling silage (OR = 1.41, 95% CI 1.10 to
      1.82), high pesticide exposure events (OR = 1.75, 95% CI 1.39 to 2.21), and ever
      use of organochlorine (OR = 1.34, 95% CI 1.04 to 1.74) and carbamate pesticides
      (OR = 1.32, 95% CI 1.03 to 1.68) were associated with farmer's lung in mutually
      adjusted models. The insecticides DDT, lindane, and aldicarb were positively
      associated with farmer's lung among farmers. Current animal exposures, while not
      statistically significant, were positively associated with farmer's lung,
      particularly for poultry houses (OR = 1.55, 95% CI 0.93 to 2.58) and dairy cattle
      (OR = 1.28, 95% CI 0.86 to 1.89). The occupational data were more limited for
      spouses; however, we saw similar associations for dairy cattle (OR = 1.50, 95% CI
      0.72 to 3.14) and organochlorine pesticides (OR = 1.29, 95% CI 0.64 to 2.59).
      CONCLUSION: While historic farm exposures may contribute to the observed
      associations with pesticides, these results suggest that organochlorine and
      carbamate pesticides should be further evaluated as potential risk factors for
      farmer's lung

PMID- 17182643
TI  - Hospital injury rates in relation to socioeconomic status and working conditions.
AB  - OBJECTIVES: To describe the risk of work injury by socioeconomic status (SES) in
      hospital workers, and to assess whether SES gradient in injury risk is explained
      by differences in psychosocial, ergonomic or organisational factors at work.
      METHODS: Workforce rosters and Occupational Safety and Health Administration
      injury logs for a 5-year period were obtained from two hospitals in
      Massachusetts. Job titles were classified into five SES strata on the basis of
      educational requirements and responsibilities: administrators, professionals,
      semiprofessionals, skilled and semiskilled workers. 13 selected psychosocial,
      ergonomic and organisational exposures were assigned to the hospital jobs through
      the national O*NET database. Rates of injury were analysed as frequency records
      using the Poisson regression, with job title as the unit of analysis. The risk of
      injury was modelled using SES alone, each exposure variable alone and then each
      exposure variable in combination with SES. RESULTS: An overall annual injury rate
      of 7.2 per 100 full-time workers was estimated for the two hospitals combined.
      All SES strata except professionals showed a significant excess risk of injury
      compared with the highest SES category (administrators); the risk was highest
      among semiskilled workers (RR 5.3, p<0.001), followed by nurses (RR 3.7,
      p<0.001), semiprofessionals (RR 2.9, p = 0.006) and skilled workers (RR 2.6, p =
      0.01). The risk of injury was significantly associated with each exposure
      considered except pause frequency. When workplace exposures were introduced in
      the regression model together with SES, four remained significant predictors of
      the risk of injury (decision latitude, supervisor support, force exertion and
      temperature extremes), whereas the RR related to SES was strongly reduced in all
      strata, except professionals. CONCLUSIONS: A strong gradient in the risk of
      injury by SES was reported in a sample population of hospital workers, which was
      greatly attenuated by adjusting for psychosocial and ergonomic workplace
      exposures, indicating that a large proportion of that gradient can be explained
      by differences in working conditions.

PMID- 17182644
TI  - Air pollution and doctors' house calls for respiratory diseases in the Greater
      Paris area (2000-3).
AB  - This study describes the short-term relationships between the daily levels of
      PM10, PM2.5, NO2 and the number of doctors' house calls for asthma, upper
      respiratory diseases (URD) and lower respiratory diseases (LRD) in Greater Paris
      for the years 2000-3. Doctors' house calls are a relevant health indicator for
      the study of short-term health effects of air pollution. Indeed, it is
      potentially more sensitive than indicators such as general hospital admissions
      due to the severity of diseases motivating the call. In this study, time-series
      analysis was used. The daily numbers of doctor's house calls were adjusted for
      time trends, seasonal factors, day of the week, influenza, weather and pollen. Up
      to 15 days of lag between exposure and health effects was considered using
      distributed lag models. A total of about 1,760,000 doctors' house calls for all
      causes occurred during the study period, among which 8027 were for asthma, 52,928
      for LRD and 74,845 for URD. No significant increase in risk was found between air
      pollution and doctors' house calls for asthma. No significant association was
      found between NO2 and doctors' house calls. An increase of 10 microg/m3 in the
      mean levels of PM10 and PM2.5 encountered during the 3 previous days was
      associated with an increase of 3% (0.8% and 5.3%) and 5.9% (2.9% and 9.0%) in the
      number of doctor's house calls for URD and LRD, respectively. Considering up to
      15 days between exposure and health outcomes, effects persist until 4 days after
      exposure and then decrease progressively. No morbidity displacement was observed.
      This study shows a significant heath effect of ambient particles (PM2.5 and
      PM10). When compared to the RRs obtained for mortality or hospital admissions in
      the same area, the values of the RRs obtained in this study confirm the higher
      sensibility of doctor's house calls for respiratory diseases as a health
      indicator.

PMID- 17182645
TI  - Assessment of exposure to mercury from industrial emissions: comparing "distance
      as a proxy" and dispersion modelling approaches.
AB  - BACKGROUND: The Runcorn area, north-west England, contains many pollution
      sources, the health effects of which have been under discussion for over 100
      years. Preliminary investigations revealed an excess risk of mortality from
      kidney disease in people living nearest to several point sources of pollution,
      using distance as a proxy for exposure. Ongoing epidemiological investigations
      into the effect of ambient mercury exposure on dose and renal effect required a
      more refined assessment of exposure. METHODS: Atmospheric dispersion modelling
      was used to assess mercury dispersion from three mercury-emitting sources
      (including a large chlor alkali plant), based on knowledge of emissions, local
      meteorology and topography. RESULTS: The model was sensitive to various input
      parameters, with different dispersion patterns and ground-level concentrations,
      and therefore different exposed populations identified when different input
      parameters were defined. The different approaches to exposure assessment also had
      an impact on the epidemiological findings. The model output correlated well with
      weekly monitoring data collected in the local area, although the model
      underestimated concentrations in close proximity to the chlor alkali plant. The
      model identified that one point source did not contribute significantly to ground
      level mercury concentrations, so that inclusion of this source when using the
      "distance as a proxy" approach led to significant exposure misclassification.
      CONCLUSIONS: The model output indicates that assessment of ambient exposure
      should give consideration to the magnitude of emissions, point source
      characteristics, local meteorology and topography to ensure that the most
      appropriate exposure classification is reached. Even if dispersion modelling
      cannot be undertaken, these data can be used to inform and improve the distance
      as a proxy approach, and improve the interpretability of the epidemiological
      findings.

PMID- 17182646
TI  - Percutaneous absorption of aromatic amines in rubber industry workers: impact of
      impaired skin and skin barrier creams.
AB  - BACKGROUND: Several aromatic amines (AA) could cause bladder cancer and are an
      occupational hygiene problem in the workplace. However, little is known about the
      percutaneous absorption of chemicals via impaired skin and about the efficacy of
      skin protection measures to reduce internal exposure. AIMS: To determine the
      impact of skin status and of skin protection measures on the internal exposure to
      AA in workers manufacturing rubber products. METHODS: 51 workers occupationally
      exposed to aniline and o-toluidine were examined. The workplace conditions, risk
      factors for skin and the use of personal protective equipment were assessed by
      means of a self-administered questionnaire. The skin of hands and forearms was
      clinically examined. Exposure to aniline and o-toluidine was assessed by ambient
      air and biological monitoring (analyses of urine samples and of haemoglobin
      adducts). RESULTS: Haemoglobin-AA-adduct levels in workers with erythema (73%)
      were significantly higher (p<0.04) than in workers with healthy skin (mean
      values: aniline 1150.4 ng/l vs 951.7 ng/l, o-toluidine 417.9 ng/l vs 118.3 ng/l).
      The multiple linear regression analysis showed that wearing gloves significantly
      reduced the internal exposure. A frequent use of skin barrier creams leads to a
      higher internal exposure of AA (p<0.03). However, the use of skincare creams at
      the workplace was associated with a reduced internal exposure (p<0.03). From
      these findings we assume that internal exposure of the workers resulted primarily
      from the percutaneous uptake. CONCLUSIONS: The study demonstrates a significantly
      higher internal exposure to AA in workers with impaired skin compared with
      workers with healthy skin. Daily wearing of gloves efficiently reduced internal
      exposure. However, an increased use of skin barrier creams enhances the
      percutaneous uptake of AA. Skincare creams seem to support skin regeneration and
      lead to reduced percutaneous uptake.

PMID- 17182647
TI  - Pain tolerance in patients presenting to primary care and physiotherapy services
      with upper limb disorders.
AB  - BACKGROUND: Arm pain is a common cause of incapacity for work and is often
      attributed to occupational activities, but in many cases the pathogenesis is
      unclear. OBJECTIVE: To investigate whether arm pain in the absence of
      identifiable underlying pathology is associated with reduced tolerance of painful
      sensory stimuli. METHODS: 133 incident cases of arm pain, recruited from primary
      care and physiotherapy services, were classified according to a validated
      diagnostic algorithm. Pain tolerance was measured at three sites in each arm in
      response to electrocutaneous stimulation. Associations with pain tolerance (the
      geometric mean of the six measurements at 5 Hz) were assessed by linear
      regression, and findings were summarised as proportional changes in pain
      tolerance. RESULTS: Pain tolerance was generally lower than in an earlier
      community survey. Women had a lower tolerance than men. After allowance for sex,
      age, use of analgesics and anatomical extent of pain, there was no indication of
      reduced tolerance in patients with non-specific pain relative to those with
      specific local pathology. CONCLUSIONS: Pain tolerance may be generally reduced in
      patients presenting to medical services with arm pain, but those with non
      specific pain do not seem to have lower tolerance than those with identifiable
      local pathology.

PMID- 17182648
TI  - Smoking and tuberculosis among silicotic patients.
AB  - The aim of the present study was to investigate the relationship between smoking
      and tuberculosis (TB) among high-risk silicotic patients in Hong Kong. A cohort
      of 435 silicotic patients tuberculin tested from 1995-2002 was prospectively
      followed-up until the end of 2005. Baseline characteristics were analysed with
      respect to positive tuberculin reaction (> or =10 mm) at baseline and subsequent
      development of TB. Smoking, alcohol use and body mass index were independent
      predictors of positive tuberculin reaction at baseline in multiple logistic
      regression analysis. Total cigarette pack-yrs did not demonstrate any significant
      effect. The annual incidences of TB were 1,841, 2,294 and 4,181 per 100,000 for
      never-, ex- and current smokers, respectively. On Cox proportional hazard
      analysis, current smokers have a significantly higher risk of TB than other
      silicotic patients (adjusted hazard ratio (95% confidence interval (CI)): 1.96
      (1.14-3.35)) after controlling for age, alcohol use, tuberculin status, treatment
      for latent TB infection and other relevant background/disease factors. A
      significant dose-response relationship was also observed with the daily number of
      cigarettes currently smoked. Smoking cessation may reduce 32.4% (95% CI: 6.5
      54.0) of the risk. Smoking increases the risk of both tuberculosis infection and
      subsequent development of the disease among silicotic patients.

PMID- 17182649
TI  - Assessment of impairment/disability due to occupational asthma through a
      multidimensional approach.
AB  - Subjects with occupational asthma (OA) are often left with permanent sequelae
      after removal from exposure, and assessing their impairment/disability should
      utilise various tools. The aim of the present study was to examine whether: 1)
      assessment of inflammation in induced sputum is relevant to impairment; and 2)
      use of questionnaires on quality of life and psychological factors can be useful
      for the evaluation of disability. In total, 40 subjects were prospectively
      assessed for permanent impairment/disability due to OA 2 yrs after cessation of
      exposure. Impairment was assessed as follows: 1) need for asthma medication; 2)
      asthma severity; 3) airway calibre and responsiveness; and 4) degree of
      inflammation in induced sputum. Disability was assessed according to quality of
      life and psychological distress. There was a significant improvement in airway
      responsiveness and inflammation from diagnosis to the present assessment. Sputum
      eosinophils > or =2% and neutrophils >60% were present in eight (20%) and 12
      (30%) out of all subjects, respectively, one or the other feature being the only
      abnormalities in 15% of subjects. Quality of life was moderately affected and
      there was a prevalence of depression and anxiety close to 50%. In the assessment
      of subjects with occupational asthma, information on airway inflammation and
      psychological impacts are relevant to the assessment of impairment/disability,
      although these findings need further investigation.

PMID- 17182650
TI  - Long-term follow-up of thoracoscopic talc pleurodesis for primary spontaneous
      pneumothorax.
AB  - The aim of the present study was to evaluate the long-term outcome of patients
      with primary spontaneous pneumothorax treated with talc pleurodesis. A follow-up
      study was undertaken in all patients with primary spontaneous pneumothorax who
      underwent talc pleurodesis for prolonged air leak or recurrence using
      thoracoscopy. In total, 112 patients underwent pleurodesis and follow-up data was
      obtained in 63 (56%) patients: 45 patients were available for clinical follow-up,
      14 for telephone follow-up and four were dead. The causes of death were unrelated
      to the pleurodesis. There were no episodes of acute respiratory failure following
      pleurodesis. A total of 56 (95%) out of the cohort of 59 patients had a
      successful pleurodesis. Surgical pleurectomy was required in three (5%) patients
      for persistent air leak. Median duration of follow-up after talc pleurodesis was
      118 months. Long-term success was observed in 53 (95%) out of 56 patients.
      Recurrent pneumothorax was observed in three (5%) out of 56 patients. Patients
      with successful talc pleurodesis had a median forced vital capacity (FVC) of 102%
      and median total lung capacity of 99% at follow-up. Comparing smokers and
      nonsmokers, the forced expiratory volume in one second (FEV(1)) was significantly
      lower in smokers and there was a tendency for the FEV(1)/FVC ratio to be lower in
      smokers. Talc pleurodesis in patients with primary spontaneous pneumothorax via
      thoracoscopy is an effective procedure associated with normal lung function in
      patients who do not smoke.

PMID- 17182651
TI  - Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension.
AB  - Pulmonary hypertension is characterised by a progressive increase in pulmonary
      arterial resistance due to endothelial and smooth muscle cell proliferation
      resulting in chronic obstruction of small pulmonary arteries. There is evidence
      that inflammatory mechanisms may contribute to the pathogenesis of human and
      experimental pulmonary hypertension. The aim of the study was to address the role
      of fractalkine (CX3CL1) in the inflammatory responses and pulmonary vascular
      remodelling of a monocrotaline-induced pulmonary hypertension model. The
      expression of CX3CL1 and its receptor CX3CR1 was studied in monocrotaline-induced
      pulmonary hypertension by means of immunohistochemistry and quantitative reverse
      transcription PCR on laser-captured microdissected pulmonary arteries. It was
      demonstrated that CX3CL1 was expressed by inflammatory cells surrounding
      pulmonary arterial lesions and that smooth muscle cells from these vessels had
      increased CX3CR1 expression. It was then shown that cultured rat pulmonary artery
      smooth muscle cells expressed CX3CR1 and that CX3CL1 induced proliferation but
      not migration of these cells. In conclusion, the current authors proposed that
      fractalkine may act as a growth factor for pulmonary artery smooth muscle cells.
      Chemokines may thus play a role in pulmonary artery remodelling.

PMID- 17182652
TI  - Cystic fibrosis mortality and survival in the UK: 1947-2003.
AB  - Data up to 1995 on the survival of 3-yr cohorts of patients with cystic fibrosis
      (CF) born in the UK in the period 1968-1992 have previously been published. The
      present study reports survival data up to the end of 2003 together with a 2003
      population estimate. All subjects with CF born in the UK in the period 1968-1992
      were identified up to 1997 by active enquiry through recognised CF clinics and
      other hospital consultants. Information from the death certification authorities
      up to the end of 2003 was added. Death certificates that could not be matched
      with UK Cystic Fibrosis Survey records were investigated and the data reconciled.
      The observed survival up to 2003 of CF patients born in 1978 was 55% for males
      and 49% for females. For 1988 and 1992 the data were 91 and 88%, and 97 and 96%,
      respectively. The estimated 2003 mid-year CF population was 8,284. The continuing
      improvement in survival of cystic fibrosis patients in successive cohorts means
      that the previous prediction of median survival of >50 yrs of age for individuals
      born in 2000 continues to look realistic, even in the absence of proven effective
      therapy aimed at correcting the basic cystic fibrosis defect.

PMID- 17182653
TI  - Mitochondrial dysfunction in COPD patients with low body mass index.
AB  - Patients with chronic obstructive pulmonary disease (COPD) show abnormal
      adaptations of skeletal muscle redox status after exercise training. Increased
      skeletal muscle oxidative stress in COPD patients may prompt mitochondrial
      dysfunction. The present study explores the association between body composition
      and mitochondrial respiration in seven COPD patients with low body mass index
      (BMI(L)), eight COPD patients with normal body mass index (BMI(N)) and seven
      healthy controls. All of them underwent a vastus lateralis biopsy in which muscle
      structure, in vitro mitochondrial respiratory function, uncoupling protein 3
      (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and
      the whole muscle were determined. Mitochondrial respiratory function (assessed by
      acceptor control ratio (ACR)) was impaired in BMI(L) (2.2+/-0.6) compared with
      both BMI(N) (5.3+/-1.3) and controls (8.2+/-1.3). ACR significantly correlated
      with arterial oxygen tension and with muscle endurance but it showed a negative
      association with exercise-induced increase in blood lactate levels. UCP3 mRNA
      expression was reduced in BMI(L) patients. In conclusion, chronic obstructive
      pulmonary disease patients with low body mass index show electron transport chain
      dysfunction, which may contribute to low muscle endurance in the current subgroup
      of patients.

PMID- 17182654
TI  - Diagnostic value of serum precipitins to mould antigens in active
      hypersensitivity pneumonitis.
AB  - Serum precipitins have a controversial diagnostic value in hypersensitivity
      pneumonitis (HP). The present authors' objective was to assess their diagnostic
      value by developing scores from a panel of specific antigens tested by two
      techniques (electrosyneresis and double diffusion) to discriminate active HP from
      other interstitial lung diseases. Consecutive patients presenting with a
      condition for which HP was considered in the differential diagnosis were included
      in the study. All patients underwent the same standardised diagnostic procedure,
      including precipitin tests performed in routine conditions. Clinical
      manifestations, bronchoalveolar lavage and high-resolution computed tomography
      defined the presence or absence of HP. Receiver-operating characteristic curves
      and logistic regression were used to develop the serological scores. A total of
      122 patients (including 31 cases of HP) were included in the study. Five antigens
      from the panel were selected for the serological scores (Absidia corymbifera,
      Eurotium amstelodami, Wallemia sebi, Saccharopolyspora rectivirgula and
      mesophilic Streptomyces sp.). Electrosyneresis was more discriminative than the
      double-diffusion technique. Predictive negative values varied 81-88% and
      predictive positive values varied 71-75% for prevalence of HP 20-35%. In
      conclusion, serological scores using a panel of relevant antigens may guide both
      biological and clinical practice in areas of high prevalence of hypersensitivity
      pneumonitis.

PMID- 17182655
TI  - Genotypes and phenotypes in children with short stature: clinical indicators of
      SHOX haploinsufficiency.
AB  - BACKGROUND: Short stature affects approximately 2% of children, representing one
      of the more frequent disorders for which clinical attention is sought during
      childhood. Despite assumed genetic heterogeneity, mutations or deletions of the
      short stature homeobox-containing gene (SHOX) are found quite frequently in
      subjects with short stature. Haploinsufficiency of the SHOX gene causes short
      stature with highly variable clinical severity, ranging from isolated short
      stature without dysmorphic features to Leri-Weill syndrome, and with no
      functional copy of the SHOX gene, Langer syndrome. METHODS: To characterise the
      clinical and molecular spectrum of SHOX deficiency in childhood we assessed the
      association between genotype and phenotype in a large cohort of children of short
      stature from 14 countries. RESULTS: Screening of 1608 unrelated individuals with
      sporadic or familial short stature revealed SHOX mutations or deletions in 68
      individuals (4.2%): complete deletions in 48 (70.6%), partial deletions in 4
      (5.9%) and point mutations in 16 individuals (23.5%). Although mean height
      standard deviation score (SDS) was not different between participants of short
      stature with or without identified SHOX gene defects (-2.6 vs -2.6), detailed
      examination revealed that certain bone deformities and dysmorphic signs, such as
      short forearm and lower leg, cubitus valgus, Madelung deformity, high-arched
      palate and muscular hypertrophy, differed markedly between participants with or
      without SHOX gene defects (p<0.001). Phenotypic data were also compared for 33
      children with Turner syndrome in whom haploinsufficiency of SHOX is thought to be
      responsible for the height deficit. CONCLUSION: A phenotype scoring system was
      developed that could assist in identifying the most appropriate subjects for SHOX
      testing. This study offers a detailed genotype-phenotype analysis in a large
      cohort of children of short stature, and provides quantitative clinical
      guidelines for testing of the SHOX gene.

PMID- 17182656
TI  - Uterine tumour resembling ovarian sex cord tumour is an immunohistochemically
      polyphenotypic neoplasm which exhibits coexpression of epithelial, myoid and sex
      cord markers.
AB  - AIMS: To describe the clinicopathological and immunohistochemical findings in
      four cases of uterine tumour resembling ovarian sex cord tumour (UTROSCT).
      METHODS: Four UTROSCTs were stained with a wide range of antibodies, including
      epithelial (AE1/3, epithelial membrane antigen), myoid (desmin, alpha smooth
      muscle actin, h-caldesmon), sex cord (alpha inhibin, calretinin, melan A, CD99)
      and neuroendocrine (chromogranin, CD56) markers as well as hormone receptors
      (oestrogen receptor, progesterone receptor, androgen receptor), vimentin, CD10,
      WT1 and HMB45. RESULTS: The tumours ranged from 0.8 to 19.5 cm. Three were
      relatively well circumscribed intramural myometrial lesions; the other was a
      pedunculated mass attached to the uterine serosa. The tumours were variably
      composed of solid, corded, trabecular, nested, glandular and retiform
      arrangements of tumour cells. In three cases, cells with eccentric nuclei and
      abundant eosinophilic cytoplasm, resulting in a rhabdoid appearance, were a
      prominent feature. Three cases were diffusely positive with AE1/3 and all with
      epithelial membrane antigen. Positivity with myoid markers was common with 3, 4
      and 1 case respectively staining with desmin, alpha smooth muscle actin and h
      caldesmon; 2, 4, 1 and 2 cases respectively were positive with alpha inhibin,
      calretinin, melan A and CD99. All were chromogranin negative and exhibited
      diffuse strong staining with CD56. All were diffusely positive with oestrogen
      receptor, progesterone receptor, vimentin and WT1. Three cases were androgen
      receptor positive and all were CD10 and HMB45 negative. CONCLUSIONS: UTROSCT
      exhibits a polyphenotypic immunophenotype with coexpression of markers of
      epithelial, myoid and sex cord lineage as well as hormone receptors.

PMID- 17182657
TI  - Non-operative breast pathology: columnar cell lesions.
AB  - The term "columnar cell lesions" encompasses a spectrum of processes,
      characterised by variably dilated acini, lined by one to several layers of
      tightly packed, columnar-shaped epithelial cells. These lesions have received
      renewed attention in the literature due to their high prevalence in biopsy
      specimens taken for assessment of mammographically detected microcalcification.
      In addition, increasing interest has been directed at the sub-set of columnar
      cell lesions with varying degrees of cytological atypia. Recent observational and
      molecular genetic studies have provided strong circumstantial evidence to suggest
      that at least some of these lesions may represent the earliest morphologically
      identifiable, non-obligate precursor of low grade breast carcinomas. However, the
      risk of both local recurrence and progression to invasive cancer appears to be
      exceedingly low. This review provides an update on recent clinicopathological and
      molecular data on columnar cell lesions and how these have changed our perception
      of, and the classification system for, these lesions. In addition, guidelines for
      the management of patients with columnar cell lesions diagnosed in core needle
      biopsy specimens are provided.

PMID- 17182658
TI  - Use of multiple displacement amplification in the investigation of human
      papillomavirus physical status.
AB  - BACKGROUND AND AIMS: The investigation of human papillomavirus (HPV) physical
      status in pre-invasive cervical lesions has been restricted by the small amounts
      of tissue available for study. Multiple displacement amplification (MDA), a phi29
      DNA polymerase based whole genome amplification technique, has the potential to
      help resolve this problem by yielding large amounts of high molecular weight DNA
      from tiny starting quantities. METHODS: Firstly, a comparison was made of
      restriction endonuclease fragment patterns of DNA from seven different HPV types
      and corresponding MDA products. Secondly, E6/E7 and LCR sequencing data from
      HPV16 recombinant plasmid and MDA copy DNA were correlated. Thirdly, DNA and MDA
      products from cervical cell lines (CaSki, HeLa, and SiHa that contain integrated
      HPV) and an invasive cervical carcinoma were analysed by Southern blot
      hybridisation. Fourthly, MDA product from CaSki cell DNA mixed with HPV18-plasmid
      DNA was tested for the demonstration of both episomal and integrated HPV.
      Finally, MDA products from HPV16 positive abnormal cervical cytological samples
      were assayed for integration by Southern blot hybridisation. RESULTS: DNA
      templates and MDA products yielded analogous data. Episomal and integrated HPV
      DNA were successfully detected by Southern blot assay of the cell line/HPV
      plasmid model, and in MDA products of clinical samples. CONCLUSIONS: These data
      show that MDA has considerable potential to assist in the investigation of HPV
      physical status; abundant (>40 microg) DNA can be generated with high fidelity
      from minuscule (50 ng) starting quantities, and both episomal and integrated HPV
      DNA are distinguishable in MDA products from solid tumours and cytological
      materials.

PMID- 17182659
TI  - Group B streptococcus prevalence in pregnant women from North-Eastern Italy:
      advantages of a screening strategy based on direct plating plus broth enrichment.
AB  - AIMS: To assess the sensitivity of a combined selective broth enrichment
      technique plus selective plating for the detection of group B streptococcus (GBS)
      colonisation in a large cohort of pregnant women from North-Eastern Italy.
      METHODS: During 2002-2005, 5020 pregnant women were screened between the 35th and
      the 37th week of gestation. A lower vaginal sample and a rectal sample were
      collected and inoculated onto LIM broth and a selective colistin aztreonam blood
      agar plate (CAP). Direct agar plates were examined after 18-24 hours and, if
      negative, after 48 hours. LIM broth was subcultured after 18-24 hours onto a
      Columbia blood agar plate. All colonies suggestive for GBS were submitted to
      phenotypic identification. RESULTS: 901 Women (17.9%) were positive for GBS. On
      728 positive samples, corresponding to patients enrolled between 2003 and 2005,
      the results of selective direct plating and selective broth enrichment were
      compared. A total of 561 (77.1% of positive samples, corresponding to 13.9% of
      patients) were positive on direct selective agar; an additional 167 isolates
      (22.9% of samples, 4.1% of patients) were recovered from the LIM broth
      subculture. CONCLUSIONS: The prevalence of GBS carriage in this population-based
      study is a reliable estimate considering the sensitivity of the microbiological
      methods used, the rate of attendance of pregnant women to clinical and laboratory
      settings and the compliance to the protocol. Results confirm that the combination
      of selective enrichment broth and selective direct plating is a time-saving and
      sensitive method.

PMID- 17182660
TI  - Melanoma histopathology reporting: are we complying with the National Minimum
      Dataset?
AB  - BACKGROUND: The Royal College of Pathologists introduced the National Minimum
      Dataset (NMDS) for the histopathological reporting of cutaneous melanoma in
      February 2002. AIM: To determine if histological reporting of invasive primary
      cutaneous melanoma in the West Midlands region of the UK was compliant with the
      NMDS. METHODS: Reports were identified from March 2002 to March 2003 via the
      regional Cancer Intelligence Unit, and compared with the NMDS. If all items of
      the NMDS were adhered to, the report was considered compliant. If not compliant,
      the report was checked to see if it included selected clinical and staging
      parameters. RESULTS: 543 cases of invasive cutaneous melanoma were identified,
      but only 407 reports were analysed. 69/407 (17%) (95% CI 14% to 20%) reports were
      fully compliant with the NMDS. Of the non-complaint reports, 45/361 (12%) (95% CI
      9% to 16%) reported all staging and clinically relevant parameters; 62/361 (17%)
      (95% CI 59% to 65%) reported all staging parameters. Breslow thickness was
      reported in all but one of the reports (99.7%), Clark's level was reported in
      344/407 (85%), ulceration in 280/407 (69%), and microsatellites in 146/407 (36%).
      CONCLUSION: There was slow uptake of the NMDS in this region in the year
      following its introduction. Although major parameters required for staging were
      more consistently reported, ulceration and microsatellites were less frequently
      reported.

PMID- 17182661
TI  - Non-operative breast pathology: lobular neoplasia.
AB  - Lobular neoplasia is a relatively uncommon lesion, which is frequently diagnosed
      in biopsy specimens taken for other reasons. Although the histological features
      of this lesion are well known, its biological significance as a "risk indicator"
      or "breast cancer precursor" has been a matter of debate. This review provides an
      update on recent clinicopathological and molecular data on lobular neoplasia and
      how these have changed the way these lesions are perceived and, most importantly,
      managed. Furthermore, the current recommendations for the management of lobular
      neoplasia diagnosed on core needle biopsies proposed in the National Health
      Service Breast Cancer Screening guidelines are discussed.

PMID- 17182662
TI  - Selecting immunohistochemical cut-off scores for novel biomarkers of progression
      and survival in colorectal cancer.
AB  - BACKGROUND: Cut-off scores for determining positivity of biomarkers detected by
      immunohistochemistry are often set arbitrarily and vary between reports. AIMS: To
      evaluate the performance of receiver operating characteristic (ROC) curve
      analysis in determining clinically important cut-off scores for a novel tumour
      marker, the receptor for hyaluronic acid mediated motility (RHAMM), and show the
      reproducibility of the selected cut-off scores in 1197 mismatch-repair (MMR)
      proficient colorectal cancers (CRC). METHODS: Immunohistochemistry for RHAMM was
      performed using a tissue microarray of 1197 MMR-proficient CRC. Immunoreactivity
      was scored using a semi-quantitative scoring method by evaluating the percentage
      of positive tumour cells. ROC curve analysis was performed for T stage, N stage,
      tumour grade, vascular invasion and survival. The score with the shortest
      distance from the curve to the point with both maximum sensitivity and
      specificity, i.e. the point (0.0, 1.0), was selected as the cut-off score leading
      to the greatest number of tumours correctly classified as having or not having
      the clinical outcome. In order to determine the reliability of the selected cut
      off scores, 100 bootstrapped replications were performed to resample the data.
      RESULTS: The cut-off score for T stage, N stage, tumour grade and vascular
      invasion was 100% and that for survival 90%. The most frequently selected cut-off
      score from the 100 resamples was also 100% for T stage, N stage, tumour grade,
      and vascular invasion and 90% for survival. CONCLUSIONS: ROC curve analysis can
      be used as an alternative method in the selection and validation of cut-off
      scores for determining the clinically relevant threshold for immunohistochemical
      tumour positivity.

PMID- 17182663
TI  - Follicular lymphoma with trisomy 18 exhibiting loss of BCL-2 expression on
      transformation to a large cell lymphoma.

PMID- 17182664
TI  - Spectral restoration and energy resolution improvement of electron energy-loss
      spectra by Pixon reconstruction: II. Application to practical ELNES analysis of
      low SNR.
AB  - We applied Pixon deconvolution as introduced in Part I to several practical,
      examples of low signal-to-noise ratio (SNR), electron energy-loss spectra with a
      goal toward restoring their fine spectral features and/or improving the energy
      resolution. We demonstrate that by directly fitting the two-dimensional spectral
      data recorded on the CCD; the method enables us to reveal fine spectral
      structures. Consequently, Pixon reconstruction extends the ability to probe
      electronic states in very spatially localized areas, a capability currently
      unique to our method.

PMID- 17182665
TI  - Deep dyspareunia and sex life after laparoscopic excision of endometriosis.
AB  - BACKGROUND: Among subjects with endometriosis and deep dyspareunia (DD), those
      with endometriosis of the uterosacral ligament (USLE) have the most severe
      impairment of sexual function. This study examines the effect of laparoscopic
      excision of endometriosis on DD and quality of sex life. METHODS: This
      observational cohort prospective study included 68 women with endometriosis
      suffering DD (intensity of pain >or= 6 on a 10-cm visual analogue scale).
      Patients underwent laparoscopic full excision of endometriosis. Following
      surgery, they were asked to use nonhormonal contraception devices. Before
      surgery, at 6- and at 12-month follow-up, patients answered a self-administered
      questionnaire based on the Sexual Satisfaction Subscale of the Derogatis Sexual
      Functioning Inventory. RESULTS: At 6- and 12-month follow-up, women with and
      without USLE had significant improvement in DD. Subjects with USLE reported
      increased variety in sex life, increased frequency of intercourse, more
      satisfying orgasms with sex, relaxing more easily during sex and being more
      relaxed and fulfilled after sex. Similar improvements were observed among women
      without USLE; however, for some variables statistical significance was not
      reached. CONCLUSIONS: Surgical excision of endometriosis improves not only DD but
      also the quality of sex life.

PMID- 17182666
TI  - Prospective cross-validation of three methods of predicting failing pregnancies
      of unknown location.
AB  - BACKGROUND: We compared the performance of each of three tests for predicting
      pregnancy failure in the pregnancy of unknown (PUL) population. METHODS: In a
      prospective observational study, we compared the performance of three models for
      the prediction of pregnancy failure in women with a PUL: (i) logistic-regression
      model incorporating vaginal bleeding, endometrial thickness (ET), initial serum
      progesterone and hCG levels; (ii) serum progesterone at 0 h; and (3) the hCG
      ratio. RESULTS: A total of 5942 consecutive pregnant women attending the Early
      Pregnancy Unit were scanned and 439 (7.4%) were classified as PULs. Of these
      women, 420 had complete data for serum hCG at 0 and 48 h, the hCG ratio, serum
      progesterone at 0 h, vaginal bleeding and ET. The final outcomes were 219 (52.1%)
      failing PULs, 167 (39.8%) intra-uterine pregnancies and 34 (8.1%) ectopic
      pregnancies. For the prediction of pregnancy failure in the PUL population, the
      area under the receiver operating characteristic (ROC) curve (AUC) for the
      logistic-regression model was 0.907 (Standard error (SE) 0.015), the AUC for
      serum progesterone was 0.952 (SE 0.010) and the AUC for the hCG ratio was 0.980
      (SE 0.004). This improved performance of the hCG ratio was significant when
      compared with that of initial serum progesterone (P = 0.0076) and the logistic
      regression model (P < 0.0001). Using the hCG ratio cut-offs of < 0.87 and
      <or=0.79, the serum progesterone cut-off of < 20 nmol l(-1) and the logistic
      regression cut-off of >70% for the prediction of failing PUL, sensitivities were
      86.3 and 82.2% (S), 87.2% (NS) and 78.1% (S), specificities were 97.0 and 98.0%
      (NS), 89.6% (S) and 88.6% (S), positive-likelihood ratios were 28.91, 41.30, 8.34
      and 6.82 and negative-likelihood ratios were 0.14, 0.18, 0.14 and 0.25,
      respectively. CONCLUSION: The hCG ratio seems to be an optimal test for the
      prediction of pregnancy failure in a PUL population. The hCG ratio cut-off of
      0.79 is recommended on the basis of minimizing risk to those PULs discharged at
      48 h. Most importantly, when the hCG ratio is below a particular cut-off, these
      women can be discharged at 48 h without intervention and need for further follow
      up.

PMID- 17182667
TI  - The effect of exercise on outcomes for hospitalised older acute medical patients:
      an individual patient data meta-analysis.

PMID- 17182668
TI  - Judgments of infant pain: the impact of caregiver identity and infant age.
AB  - OBJECTIVE: To examine whether caregiver judgments of infant pain would vary
      systematically with different infant caregiver groups and infant age. METHODS: A
      total of 123 caregivers (41 parents, 41 in patient nurses, 41 pediatricians)
      viewed videotapes of the vigorous behavioral responses of healthy infants (aged
      2, 4, 6, 12, and 18 months) to a routine immunization injection and provided
      ratings of both the affective distress and pain intensity observed. RESULTS: A
      principal components analysis of affective and intensity ratings yielded a
      weighted pain summary score for each injection event. Older infants were
      attributed significantly more pain than younger infants, even though the vigor of
      the behavioral reactions was experimentally controlled across age groups. A
      profile analysis contrasting observer groups indicated that pediatricians
      attributed significantly lower levels of pain than parents, while nurses were
      intermediate to the other groups, not significantly differing from either group.
      These systematic differences in judgments were consistent across infant age
      groups. CONCLUSIONS: The findings reveal systematic sources of significant
      variations in observer judgments of infant pain. Despite an absence of
      differences in the behavioral reactions of the children, both the type of
      caregiver and their knowledge of the child's age systematically influenced
      attributions of pain to infants. This work suggests the important role of
      caregiver role variation and perceived developmental maturity as determinants of
      infant pain judgments and highlights potential areas of difficulty in controlling
      the unnecessary suffering of infants.

PMID- 17182669
TI  - Psychological and cognitive functioning in children and adolescents with
      congenital heart disease: a meta-analysis.
AB  - OBJECTIVE: Findings in the literature are inconsistent on the impact of
      congenital heart disease (CHD) on the psychological and cognitive functioning of
      children and adolescents. The aim of the present study was to systematically
      review this empirical body of literature. METHODS: We conducted a meta-analysis
      to review studies on behavior problems and cognitive functioning in CHD. RESULTS:
      Only older children and adolescents with CHD displayed an increased risk of
      overall, internalizing, and to a lesser extent externalizing behavior problems.
      In addition, patients with severe CHD exhibited lower cognitive functioning than
      patients with less severe CHD, specifically with respect to performance
      intelligence. Moreover, decreased cognitive functioning remained relatively
      stable across different age groups. CONCLUSIONS: Children with severe heart
      disease may benefit from interventions specifically targeting perceptual
      organizational abilities, such as visual-spatial abilities. Moreover, older
      children and adolescents with CHD may benefit from psychological interventions
      reducing anxiety symptoms and depression.

PMID- 17182670
TI  - Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection
      display an exhausted phenotype with high levels of PD-1 and low levels of CD127
      expression.
AB  - The majority of people infected with hepatitis C virus (HCV) fail to generate or
      maintain a T-cell response effective for viral clearance. Evidence from murine
      chronic viral infections shows that expression of the coinhibitory molecule PD-1
      predicts CD8+ antiviral T-cell exhaustion and may contribute to inadequate
      pathogen control. To investigate whether human CD8+ T cells express PD-1 and
      demonstrate a dysfunctional phenotype during chronic HCV infection, peripheral
      and intrahepatic HCV-specific CD8+ T cells were examined. We found that in
      chronic HCV infection, peripheral HCV-specific T cells express high levels of PD
      1 and that blockade of the PD-1/PD-L1 interaction led to an enhanced
      proliferative capacity. Importantly, intrahepatic HCV-specific T cells, in
      contrast to those in the periphery, express not only high levels of PD-1 but also
      decreased interleukin-7 receptor alpha (CD127), an exhausted phenotype that was
      HCV antigen specific and compartmentalized to the liver, the site of viral
      replication.

PMID- 17182671
TI  - Human immunodeficiency virus type 1 pathobiology studied in humanized BALB/c-Rag2
      /-gammac-/- mice.
AB  - The specificity of human immunodeficiency virus type 1 (HIV-1) for human cells
      precludes virus infection in most mammalian species and limits the utility of
      small animal models for studies of disease pathogenesis, therapy, and vaccine
      development. One way to overcome this limitation is by human cell
      xenotransplantation in immune-deficient mice. However, this has proved
      inadequate, as engraftment of human immune cells is limited (both functionally
      and quantitatively) following transplantation of mature human lymphocytes or
      fetal thymus/liver. To this end, a human immune system was generated from
      umbilical cord blood-derived CD34(+) hematopoietic stem cells in BALB/c-Rag2(-/
      )gamma(c)(-/-) mice. Intrapartum busulfan administration followed by irradiation
      of newborn pups resulted in uniform engraftment characterized by human T-cell
      development in thymus, B-cell maturation in bone marrow, lymph node development,
      immunoglobulin M (IgM)/IgG production, and humoral immune responses following
      ActHIB vaccination. Infection of reconstituted mice by CCR5-coreceptor utilizing
      HIV-1(ADA) and subtype C 1157 viral strains elicited productive viral replication
      and lymphadenopathy in a dose-dependent fashion. We conclude that humanized
      BALB/c-Rag2(-/-)gamma(c)(-/-) mice represent a unique and valuable resource for
      HIV-1 pathobiology studies.

PMID- 17182672
TI  - Tissue-specific regulation of CD8+ T-lymphocyte immunodominance in respiratory
      syncytial virus infection.
AB  - Cytotoxic T lymphocytes (CTLs) are critical for control of respiratory syncytial
      virus (RSV) infection in humans and mice. To investigate cellular immune
      responses to infection, it is important to identify major histocompatibility
      complex (MHC) class I-restricted CTL epitopes. In this study, we identified a new
      RSV-specific, H-2K(d)-restricted subdominant epitope in the M2 protein, M2(127
      135) (amino acids 127 to 135). This finding allowed us to study the frequency of
      T lymphocytes responding to two H-2K(d)-presented epitopes in the same protein
      following RSV infection by enzyme-linked immunospot (ELISPOT) and intracellular
      cytokine assays for both lymphoid and nonlymphoid tissues. For the subdominant
      epitope, we identified an optimal nine-amino-acid peptide, VYNTVISYI, which
      contained an H-2K(d) consensus sequence with Y at position 2 and I at position 9.
      In addition, an MHC class I stabilization assay using TAP-2-deficient RMA-S cells
      transfected with K(d) or L(d) indicated that the epitope was presented by K(d).
      The ratios of T lymphocytes during the peak CTL response to RSV infection that
      were specific for M2(82-90) (dominant) to T lymphocytes specific for M2(127-135)
      (subdominant) were approximately 3:1 in the spleen and 10:1 in the lung. These
      ratios were observed consistently in primary or secondary infection by the
      ELISPOT assay and in secondary infection by MHC/peptide tetramer staining. The
      number of antigen-specific T lymphocytes dropped in the 6 weeks after infection;
      however, the proportions of T lymphocytes specific for the immunodominant and
      subdominant epitopes were maintained to a remarkable degree in a tissue-specific
      manner. These studies will facilitate investigation of the regulation of
      immunodominance of RSV-specific CTL epitopes.

PMID- 17182673
TI  - Herpesvirus saimiri STP-A oncoprotein utilizes Src family protein tyrosine kinase
      and tumor necrosis factor receptor-associated factors to elicit cellular signal
      transduction.
AB  - The saimiri transforming protein oncogene, called STP-A, of herpesvirus saimiri
      (HVS) subgroup A is not required for viral replication but is required for
      lymphoid cell immortalization in culture and lymphoma induction in primates. Here
      we report that STP-A interacts with cellular tumor necrosis factor receptor
      associated factors (TRAF2 and TRAF6) and Src family protein tyrosine kinases (SF
      PTKs) in a genetically and functionally separable manner and that each
      interaction constitutively elicits independent cellular signal transduction. The
      amino-terminal and central proline-rich motifs of STP-A were responsible for
      TRAF6 and TRAF2 interactions, respectively, and STP-A and TRAF6 interaction
      contributed to the majority of NF-kappaB activation, whereas STP-A and TRAF2
      interaction played a minor role in NF-kappaB activation. On the other hand,
      interaction of STP-A with SF-PTKs through its SH2 binding motif effectively
      elicited AP-1 and NF-AT transcription factor activity. One cellular gene targeted
      by STP-A is intercellular adhesion molecule 1 (ICAM-1), which participates in a
      wide range of inflammatory and immune responses. Both TRAF and SF-PTK signal
      transductions induced by STP-A were required for the marked increase of ICAM-1
      expression. These results demonstrate that the viral oncogene STP-A independently
      targets two vital cellular signaling molecules and that these activities likely
      contribute to HVS-mediated lymphoid cell immortalization in culture and lymphoma
      induction in primates.

PMID- 17182674
TI  - The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes
      with human immunodeficiency virus type 1 Gag particle production.
AB  - The human immunodeficiency virus type 1 (HIV-1) Gag protein recruits Tsg101 to
      facilitate HIV-1 particle budding and release. In uninfected cells, the Hrs
      protein recruits the ESCRT-I complex to the endosome, also through an interaction
      with Tsg101, to promote the sorting of host proteins into endosomal vesicles and
      multivesicular bodies. Here, we show that the overexpression of the C-terminal
      fragment of Hrs (residues 391 to 777) or Hrs mutants lacking either the N
      terminal FYVE domain (mutant dFYVE) or the PSAP (residues 348 to 351) motif
      (mutant ASAA) all efficiently inhibit HIV-1 Gag particle production. Expression
      of the dFYVE or ASAA mutants of Hrs had no effect on the release of Moloney
      murine leukemia virus. Coimmunoprecipitation analysis showed that the expression
      of Hrs mutant dFYVE or ASAA significantly reduced or abolished the HIV-1 Gag
      Tsg101 interaction. Yeast-two hybrid assays were used to identify two new and
      independent Tsg101 binding sites, one in the Hrs coiled-coil domain and one in
      the proline/glutamic acid-rich domain. Scanning electron microscopy of HeLa cells
      expressing HIV-1 Gag and the Hrs ASAA mutant showed viral particles arrested in
      "lump-like" structures that remained attached to the cell surface. Together,
      these data indicate that fragments of Hrs containing the C-terminal portion of
      the protein can potently inhibit HIV-1 particle release by efficiently
      sequestering Tsg101 away from the Gag polyprotein.

PMID- 17182675
TI  - Enhancement of hepatitis B virus replication by the regulatory X protein in vitro
      and in vivo.
AB  - The 3.2-kb hepatitis B virus (HBV) genome encodes a single regulatory protein
      termed HBx. While multiple functions have been identified for HBx in cell
      culture, its role in virus replication remains undefined. In the present study,
      we combined an HBV plasmid-based replication assay with the hydrodynamic tail
      vein injection model to investigate the function(s) of HBx in vivo. Using a
      greater-than-unit-length HBV plasmid DNA construct (payw1.2) and a similar
      construct with a stop codon at position 7 of the HBx open reading frame
      (payw1.2*7), we showed that HBV replication in transfected HepG2 cells was
      reduced 65% in the absence of HBx. These plasmids were next introduced into the
      livers of outbred ICR mice via hydrodynamic tail vein injection. At the peak of
      virus replication, at 4 days postinjection, intrahepatic markers of HBV
      replication were reduced 72% to 83% in mice injected with HBx-deficient payw1.2*7
      compared to those measured in mice receiving wild-type payw1.2. A second plasmid
      encoding HBx was able to restore virus replication from payw1.2*7 to wild-type
      levels. Finally, viremia was monitored over the course of acute virus
      replication, and at 4 days postinjection, it was reduced by nearly 2 logs in the
      absence of HBx. These studies establish that the role for HBx in virus
      replication previously shown in transfected HepG2 cells is also apparent in the
      mouse liver within the context of acute hepatitis. Importantly, the function of
      HBx can now be studied in an in vivo setting that more closely approximates the
      cellular environment for HBV replication.

PMID- 17182676
TI  - Changes in paracrine interleukin-2 requirement, CCR7 expression, frequency, and
      cytokine secretion of human immunodeficiency virus-specific CD4+ T cells are a
      consequence of antigen load.
AB  - Virus-specific CD4+ T-cell responses are thought to be required for the induction
      and maintenance of many effective CD8+ T-cell and B-cell immune responses in
      experimental animals and humans. Although the presence of human immunodeficiency
      virus (HIV)-specific CD4+ T cells has been documented in patients at all stages
      of HIV infection, many fundamental questions regarding their frequency and
      function remain. A 10-color, 12-parameter flow cytometric panel was utilized to
      examine the frequency, memory phenotype (CD27, CCR7, and CD45RA), and cytokine
      production (interleukin-2 [IL-2], gamma interferon, and tumor necrosis factor
      alpha) of CD4+ T cells specific for HIV antigens as well as for adenovirus,
      Epstein-Barr virus (EBV), influenza H1N1 virus, influenza H3N2 virus,
      cytomegalovirus, varicella-zoster virus (VZV), and tetanus toxoid in normal
      controls, long-term nonprogressors (LTNP), and HIV-infected patients with
      progressive disease on or off therapy. The HIV-specific CD4+ T-cell responses in
      LTNP and patients on therapy were similar in frequency, phenotype, and cytokine
      production to responses directed against adenovirus, EBV, influenza virus, and
      VZV. HIV-specific CD4+ T cells from patients off antiretroviral therapy
      demonstrated a shift towards a CCR7(-) CD45RA(-) phenotype and a reduced
      percentage of IL-2-producing cells. The alterations in cytokine production during
      HIV viremia were found to be intrinsic to the HIV-specific CD4+ T cells and
      caused a requirement for IL-2 supplied exogenously for proliferation to occur.
      These observations suggest that many previously described changes in HIV-specific
      CD4+ T-cell function and phenotype are a consequence of high levels of antigen in
      viremic patients. In addition, defects in function and phenotype of HIV-specific
      CD4+ T cells are not readily discernible in the context of antiretroviral therapy
      but rather are similar to responses to other viruses.

PMID- 17182677
TI  - Posttranslational acetylation of the human immunodeficiency virus type 1
      integrase carboxyl-terminal domain is dispensable for viral replication.
AB  - A recent report sought to demonstrate that acetylation of specific lysines within
      integrase (IN) by the histone acetyltransferase (HAT) p300 regulates human
      immunodeficiency virus type 1 (HIV-1) integration and is essential for viral
      replication (A. Cereseto, L. Manganaro, M. I. Gutierrez, M. Terreni, A.
      Fittipaldi, M. Lusic, A. Marcello, and M. Giacca, EMBO J. 24:3070-3081, 2005). We
      can corroborate the efficient and specific acetylation of the IN carboxyl
      terminal domain (CTD) (amino acids 212 to 288) by p300 using purified recombinant
      components. Although arginine substitution mutagenesis of the isolated CTD
      confirms that the majority of p300 acetylation occurs at lysine residues 264,
      266, and 273, the pattern of acetylation is not uniform and a hierarchy of
      reactivity can be established. Several combinatorial mutations of the CTD lysines
      modified by p300 in vitro were reconstructed into an otherwise infectious
      proviral plasmid clone and examined for viral growth and frequency of productive
      chromosomal integration. In contrast to the findings of Cereseto and coworkers,
      who used epitope-tagged viruses for their experiments, we find that an untagged
      mutant virus, IN K(264/266/273)R, is fully replication competent. This
      discrepancy may be explained by the use of an acidic epitope tag placed at the
      extreme carboxyl terminus of integrase, near the target site for acetylation.
      Although the tagged, wild-type virus is viable, the combination of this epitope
      tag with the RRR substitution mutation results in a replication-defective
      phenotype. Although IN belongs to the very small set of nonhistone proteins
      modified by HAT-mediated activity, an obligate role for acetylation at the
      reactive CTD lysines in HIV-1 IN cannot be confirmed.

PMID- 17182678
TI  - Mouse hepatitis coronavirus A59 nucleocapsid protein is a type I interferon
      antagonist.
AB  - The recent emergence of several new coronaviruses, including the etiological
      cause of severe acute respiratory syndrome, has significantly increased the
      importance of understanding virus-host cell interactions of this virus family. We
      used mouse hepatitis virus (MHV) A59 as a model to gain insight into how
      coronaviruses affect the type I alpha/beta interferon (IFN) system. We
      demonstrate that MHV is resistant to type I IFN. Protein kinase R (PKR) and the
      alpha subunit of eukaryotic translation initiation factor are not phosphorylated
      in infected cells. The RNase L activity associated with 2',5'-oligoadenylate
      synthetase is not activated or is blocked, since cellular RNA is not degraded.
      These results are consistent with lack of protein translation shutoff early
      following infection. We used a well-established recombinant vaccinia virus (VV)
      based expression system that lacks the viral IFN antagonist E3L to screen viral
      genes for their ability to rescue the IFN sensitivity of the mutant. The
      nucleocapsid (N) gene rescued VVDeltaE3L from IFN sensitivity. N gene expression
      prevents cellular RNA degradation and partially rescues the dramatic translation
      shutoff characteristic of the VVDeltaE3L virus. However, it does not prevent PKR
      phosphorylation. The results indicate that the MHV N protein is a type I IFN
      antagonist that likely plays a role in circumventing the innate immune response.

PMID- 17182679
TI  - NS1 proteins of avian influenza A viruses can act as antagonists of the human
      alpha/beta interferon response.
AB  - Many viruses, including human influenza A virus, have developed strategies for
      counteracting the host type I interferon (IFN) response. We have explored whether
      avian influenza viruses were less capable of combating the type I IFN response in
      mammalian cells, as this might be a determinant of host range restriction. A
      panel of avian influenza viruses isolated between 1927 and 1997 was assembled.
      The selected viruses showed variation in their ability to activate the expression
      of a reporter gene under the control of the IFN-beta promoter and in the levels
      of IFN induced in mammalian cells. Surprisingly, the avian NS1 proteins expressed
      alone or in the genetic background of a human influenza virus controlled IFN-beta
      induction in a manner similar to the NS1 protein of human strains. There was no
      direct correlation between the IFN-beta induction and replication of avian
      influenza viruses in human A549 cells. Nevertheless, human cells deficient in the
      type I IFN system showed enhanced replication of the avian viruses studied,
      implying that the human type I IFN response limits avian influenza viruses and
      can contribute to host range restriction.

PMID- 17182680
TI  - Spatiotemporal analysis of purkinje cell degeneration relative to parasagittal
      expression domains in a model of neonatal viral infection.
AB  - Infection of newborn Lewis rats with Borna disease virus (neonatal Borna disease
      [NBD]) results in cerebellar damage without the cellular inflammation associated
      with infections in later life. Purkinje cell (PC) damage has been reported for
      several models of early-life viral infection, including NBD; however, the time
      course and distribution of PC pathology have not been investigated rigorously.
      This study examined the spatiotemporal relationship between PC death and zonal
      organization in NBD cerebella. Real-time PCR at postnatal day 28 (PND28) revealed
      decreased cerebellar levels of mRNAs encoding the glycolytic enzymes aldolase C
      (AldoC, also known as zebrin II) and phosphofructokinase C and the excitatory
      amino acid transporter 4 (EAAT4). Zebrin II and EAAT4 immunofluorescence analysis
      in PND21, PND28, PND42, and PND84 NBD rat cerebella revealed a complex pattern of
      PC degeneration. Early cell loss (PND28) was characterized by preferential
      apoptotic loss of zebrin II/EAAT4-negative PC subsets in the anterior vermis.
      Consistent with early preferential loss of zebrin II/EAAT4-negative PCs in the
      vermis, the densities of microglia and the Bergmann glial expression of
      metallothionein I/II and the hyaluronan receptor CD44 were higher in zebrin
      II/EAAT4-negative zones. In contrast, early loss in lateral cerebellar lobules
      did not reflect a similar discrimination between PC phenotypes. Patterns of
      vermal PC loss became more heterogeneous at PND42, with the loss of both zebrin
      II/EAAT4-negative and zebrin II/EAAT4-positive neurons. At PND84, zebrin II/EAAT4
      patterning was abolished in the anterior cerebellum, with preferential PC
      survival in lobule X. Our investigation reveals regional discrimination between
      patterns of PC subset loss, defined by zebrin II/EAAT4 expression domains,
      following neonatal viral infection. These findings suggest a differential
      vulnerability of PC subsets during the early stages of virus-induced
      neurodegeneration.

PMID- 17182681
TI  - Reduced maximal inhibition in phenotypic susceptibility assays indicates that
      viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound
      receptor for entry.
AB  - Maraviroc is a CCR5 antagonist in clinical development as one of a new class of
      antiretrovirals targeting human immunodeficiency virus type 1 (HIV-1) coreceptor
      binding. We investigated the mechanism of HIV resistance to maraviroc by using in
      vitro sequential passage and site-directed mutagenesis. Serial passage through
      increasing maraviroc concentrations failed to select maraviroc-resistant variants
      from some laboratory-adapted and clinical isolates of HIV-1. However, high-level
      resistance to maraviroc was selected from three of six primary isolates passaged
      in peripheral blood lymphocytes (PBL). The SF162 strain acquired resistance to
      maraviroc in both treated and control cultures; all resistant variants were able
      to use CXCR4 as a coreceptor. In contrast, maraviroc-resistant virus derived from
      isolates CC1/85 and RU570 remained CCR5 tropic, as evidenced by susceptibility to
      the CCR5 antagonist SCH-C, resistance to the CXCR4 antagonist AMD3100, and an
      inability to replicate in CCR5 Delta32/Delta32 PBL. Strain-specific mutations
      were identified in the V3 loop of maraviroc-resistant CC1/85 and RU570. The
      envelope-encoding region of maraviroc-resistant CC1/85 was inserted into an NL4-3
      background. This recombinant virus was completely resistant to maraviroc but
      retained susceptibility to aplaviroc. Reverse mutation of gp120 residues 316 and
      323 in the V3 loop (numbering from HXB2) to their original sequence restored wild
      type susceptibility to maraviroc, while reversion of either mutation resulted in
      a partially sensitive virus with reduced maximal inhibition (plateau). The
      plateaus are consistent with the virus having acquired the ability to utilize
      maraviroc-bound receptor for entry. This hypothesis was further corroborated by
      the observation that a high concentration of maraviroc blocks the activity of
      aplaviroc against maraviroc-resistant virus.

PMID- 17182682
TI  - Human papillomavirus E7 repression in cervical carcinoma cells initiates a
      transcriptional cascade driven by the retinoblastoma family, resulting in
      senescence.
AB  - This work demonstrates a central role for the retinoblastoma (Rb) family in
      driving the transcriptional program of induced and replicative senescence. HeLa
      cervical carcinoma cells rapidly undergo senescence when the human papillomavirus
      (HPV) type 18 E7 gene in these cells is repressed by the bovine papillomavirus
      (BPV) E2 protein. This senescence response requires the endogenous Rb pathway but
      not the p53 pathway. Microarray analysis 6 days after BPV E2 introduction into
      HeLa cells identified 224 cellular genes induced by E7 repression and 354
      repressed genes. Many repressed genes were involved in cell cycle progression,
      and numerous induced genes encoded lysosomal proteins. These gene expression
      changes were blocked by constitutive expression of the wild-type HPV16 E7 or
      adenovirus E1A gene, but not by E7 or E1A mutants defective for Rb binding. Short
      hairpin RNAs targeting the Rb family also inhibited these gene expression changes
      and blocked senescence. Therefore, surprisingly, the transcriptional response to
      BPV E2 expression was entirely dependent on E7 repression and activation of the
      Rb family, and the BPV E2 protein did not directly affect the expression of
      cellular genes. Activation of the Rb family repressed E2F-responsive genes and
      stimulated transcriptional activators, thereby mobilizing multiple signals, such
      as repression of B-MYB and DEK, that were independently sufficient to induce
      senescence. There was extensive overlap between the transcriptional profiles of
      senescent, late-passage primary human fibroblasts and senescent cervical
      carcinoma cells, suggesting that this Rb family-mediated transcriptional cascade
      also plays a central role in replicative senescence.

PMID- 17182683
TI  - Multiple amino acid substitutions in hemagglutinin are necessary for wild-type
      measles virus to acquire the ability to use receptor CD46 efficiently.
AB  - Measles virus (MV) possesses two envelope glycoproteins, namely, the receptor
      binding hemagglutinin (H) and fusion proteins. Wild-type MV strains isolated in B
      lymphoid cell lines use signaling lymphocyte activation molecule (SLAM), but not
      CD46, as a cellular receptor, whereas MV vaccine strains of the Edmonston lineage
      use both SLAM and CD46 as receptors. Studies have shown that the residue at
      position 481 of the H protein is critical in determining the use of CD46 as a
      receptor. However, the wild-type IC-B strain with a single N481Y substitution in
      the H protein utilizes CD46 rather inefficiently. In this study, a number of
      chimeric and mutant H proteins, and recombinant viruses harboring them, were
      generated to determine which residues of the Edmonston H protein are responsible
      for its efficient use of CD46. Our results show that three substitutions (N390I
      and E492G plus N416D or T446S), in addition to N481Y, are necessary for the IC-B
      H protein to use CD46 efficiently as a receptor. The N390I, N416D, and T446S
      substitutions are present in the H proteins of all strains of the Edmonston
      lineage, whereas the E492G substitution is found only in the H protein of the
      Edmonston tag strain generated from cDNAs. The T484N substitution, found in some
      of the Edmonston-lineage strains, resulted in a similar effect on the use of CD46
      to that caused by the E492G substitution. Thus, multiple residues in the H
      protein that have not previously been implicated have important roles in the
      interaction with CD46.

PMID- 17182684
TI  - Role of host cytokine responses in the pathogenesis of avian H5N1 influenza
      viruses in mice.
AB  - Highly pathogenic avian H5N1 influenza viruses are now widespread in poultry in
      Asia and have recently spread to some African and European countries.
      Interspecies transmission of these viruses to humans poses a major threat to
      public health. To better understand the basis of pathogenesis of H5N1 viruses, we
      have investigated the role of proinflammatory cytokines in transgenic mice
      deficient in interleukin-6 (IL-6), macrophage inflammatory protein 1 alpha (MIP
      1alpha), IL-1 receptor (IL-1R), or tumor necrosis factor receptor 1 (TNFR1) by
      the use of two avian influenza A viruses isolated from humans, A/Hong Kong/483/97
      (HK/483) and A/Hong Kong/486/97 (HK/486), which exhibit high and low lethality in
      mice, respectively. The course of disease and the extent of virus replication and
      spread in IL-6- and MIP-1alpha-deficient mice were not different from those
      observed in wild-type mice during acute infection with 1,000 50% mouse infective
      doses of either H5N1 virus. However, with HK/486 virus, IL-1R-deficient mice
      exhibited heightened morbidity and mortality due to infection, whereas no such
      differences were observed with the more virulent HK/483 virus. Furthermore, TNFR1
      deficient mice exhibited significantly reduced morbidity following challenge with
      either H5N1 virus but no difference in viral replication and spread or ultimate
      disease outcome compared with wild-type mice. These results suggest that TNF
      alpha may contribute to morbidity during H5N1 influenza virus infection, while IL
      1 may be important for effective virus clearance in nonlethal H5N1 disease.

PMID- 17182685
TI  - Synergy of small molecular inhibitors of hepatitis C virus replication directed
      at multiple viral targets.
AB  - Chronic hepatitis C virus (HCV) infection is a significant worldwide health
      problem with limited therapeutic options. A number of novel, small molecular
      inhibitors of HCV replication are now entering early clinical trials in humans.
      Resistance to small molecular inhibitors is likely to be a significant hurdle to
      their use in patients. A systematic assessment of combinations of interferon
      and/or novel anti-hepatitis C virus agents from several different mechanistic
      classes was performed in vitro. Combinations of inhibitors with different
      mechanisms of action consistently demonstrated more synergy than did compounds
      with similar mechanisms of action. These results suggest that combinations of
      inhibitors with different mechanisms of action should be prioritized for
      assessment in clinical trials for chronic hepatitis C virus infection.

PMID- 17182686
TI  - CD8 T-cell recognition of multiple epitopes within specific Gag regions is
      associated with maintenance of a low steady-state viremia in human
      immunodeficiency virus type 1-seropositive patients.
AB  - The importance of HLA class I-restricted CD8 T-cell responses in the control of
      human immunodeficiency virus (HIV) infection is generally accepted. While several
      studies have shown an association of certain HLA class I alleles with slower
      disease progression, it is not fully established whether this effect is mediated
      by HIV-specific CD8 T-cell responses restricted by these alleles. In order to
      study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell
      response and on viral control, we have assessed HIV-specific epitope recognition,
      plasma viral load, and expression of HLA class I alleles in a cohort of HIV
      seropositive bar workers. Possession of the HLA class I alleles B5801, B8101, and
      B0702 was associated with a low median viral load and simultaneously with a
      broader median recognition of Gag epitopes compared to all other HLA alleles
      (twofold increase) (P = 0.0035). We further found an inverse linear relationship
      between the number of Gag epitopes recognized and the plasma viral load (R = 
      0.36; P = 0.0016). Particularly, recognition of multiple epitopes within two
      regions of Gag (amino acids [aa] 1 to 75 and aa 248 to 500) was associated with
      the maintenance of a low steady-state viremia, even years after acute infection.

PMID- 17182687
TI  - Characterization of primary and memory CD8 T-cell responses against ranavirus
      (FV3) in Xenopus laevis.
AB  - In mammals, resistance to primary and secondary viral infections critically
      involves major histocompatibility complex class I-restricted cytotoxic CD8+ T
      lymphocytes (CTLs). Although many gene homologues involved in CTL function have
      been identified in all vertebrate classes, antiviral CTL responses have been
      poorly characterized for ectothermic vertebrates. Because of the threat of
      emerging wildlife viral diseases to global biodiversity, fundamental research on
      comparative viral immunity has become crucial. Ranaviruses (family Iridoviridae)
      are double-stranded DNA viruses possibly implicated in the worldwide decline of
      amphibian populations. We used the frog Xenopus laevis as a model to evaluate
      adaptive immune responses to the ranavirus frog virus 3 (FV3). FV3 infects the
      kidneys of adults but is cleared within 4 weeks, with faster clearance upon
      secondary infections. In vivo depletion of CD8+ T cells markedly decreases the
      survival of adults after viral infection. To further investigate the involvement
      of anti-FV3 CD8+ T-cell effectors in host resistance in vivo, we determined the
      proliferation kinetics of CD8+ T cells in the spleen by bromodeoxyuridine
      incorporation and their infiltration of kidneys by immunohistology. Upon primary
      infection, CD8+ T cells significantly proliferate in the spleen and accumulate in
      infected kidneys from day 6 onward, in parallel with virus clearance. Earlier
      proliferation and infiltration associated with faster viral clearance were
      observed during a secondary infection. These results provide in vivo evidence of
      protective antigen-dependent CD8+ T-cell proliferation, recognition, and memory
      in fighting a natural pathogen in Xenopus.

PMID- 17182688
TI  - Influenza seasonality: underlying causes and modeling theories.

PMID- 17182689
TI  - In vitro treatment of human monocytes/macrophages with myristoylated recombinant
      Nef of human immunodeficiency virus type 1 leads to the activation of mitogen
      activated protein kinases, IkappaB kinases, and interferon regulatory factor 3
      and to the release of beta interferon.
AB  - The viral protein Nef is a virulence factor that plays multiple roles during the
      early and late phases of human immunodeficiency virus (HIV) replication. Nef
      regulates the cell surface expression of critical proteins (including down
      regulation of CD4 and major histocompatibility complex class I), T-cell receptor
      signaling, and apoptosis, inducing proapoptotic effects in uninfected bystander
      cells and antiapoptotic effects in infected cells. It has been proposed that Nef
      intersects the CD40 ligand signaling pathway in macrophages, leading to
      modification in the pattern of secreted factors that appear able to recruit and
      activate T lymphocytes, rendering them susceptible to HIV infection. There is
      also increasing evidence that in vitro cell treatment with Nef induces signaling
      effects. Exogenous Nef treatment is able to induce apoptosis in uninfected T
      cells, maturation in dendritic cells, and suppression of CD40-dependent
      immunoglobulin class switching in B cells. Previously, we reported that Nef
      treatment of primary human monocyte-derived macrophages (MDMs) induces a
      cycloheximide-independent activation of NF-kappaB and the synthesis and secretion
      of a set of chemokines/cytokines that activate STAT1 and STAT3. Here, we show
      that Nef treatment is capable of hijacking cellular signaling pathways, inducing
      a very rapid regulatory response in MDMs that is characterized by the rapid and
      transient phosphorylation of the alpha and beta subunits of the IkappaB kinase
      complex and of JNK, ERK1/2, and p38 mitogen-activated protein kinase family
      members. In addition, we have observed the activation of interferon regulatory
      factor 3, leading to the synthesis of beta interferon mRNA and protein, which in
      turn induces STAT2 phosphorylation. All of these effects require Nef
      myristoylation.

PMID- 17182690
TI  - Exceptional flexibility in the sequence requirements for coronavirus small
      envelope protein function.
AB  - The small envelope protein (E) plays a role of central importance in the assembly
      of coronaviruses. This was initially established by studies demonstrating that
      cellular expression of only E protein and the membrane protein (M) was necessary
      and sufficient for the generation and release of virus-like particles. To
      investigate the role of E protein in the whole virus, we previously generated E
      gene mutants of mouse hepatitis virus (MHV) that were defective in viral growth
      and produced aberrantly assembled virions. Surprisingly, however, we were also
      able to isolate a viable MHV mutant (DeltaE) in which the entire E gene, as well
      as the nonessential upstream genes 4 and 5a, were deleted. We have now
      constructed an E knockout mutant that confirms that the highly defective
      phenotype of the DeltaE mutant is due to loss of the E gene. Additionally, we
      have created substitution mutants in which the MHV E gene was replaced by
      heterologous E genes from viruses spanning all three groups of the coronavirus
      family. Group 2 and 3 E proteins were readily exchangeable for that of MHV.
      However, the E protein of a group 1 coronavirus, transmissible gastroenteritis
      virus, became functional in MHV only after acquisition of particular mutations.
      Our results show that proteins encompassing a remarkably diverse range of primary
      amino acid sequences can provide E protein function in MHV. These findings
      suggest that E protein facilitates viral assembly in a manner that does not
      require E protein to make sequence-specific contacts with M protein.

PMID- 17182691
TI  - Role of the TSG101 gene in Epstein-Barr virus late gene transcription.
AB  - Rta, an Epstein-Barr virus (EBV)-encoded immediate-early protein, governs the
      reactivation of the viral lytic program by transactivating a cascade of lytic
      gene expression. Cellular transcription factors such as Sp1, ATF2, E2F, and Akt
      have been demonstrated to mediate Rta transactivation of lytic genes. We report
      herein that Rta associates with another potent transcription factor, tumor
      susceptibility gene 101 (TSG101), to promote the activation of EBV late genes.
      Results from an EBV cDNA array reveal that depletion of TSG101 by siRNA potently
      inhibits the transcription of five Rta-responsive EBV late genes, BcLF1, BDLF3,
      BILF2, BLLF1, and BLRF2. Depletion of TSG101 impairs the Rta transactivation of
      these late promoters severely. Moreover, a concordant augmentation of Rta
      transactivating activity is observed when TSG101 is overexpressed following
      ectopic transfection. Mechanistically, Rta interaction with TSG101 causes the
      latter to accumulate principally in the nuclei, wherein the proteins colocalize
      and are recruited to the viral promoters. Of note, TSG101 is crucial for the
      efficient binding of Rta to these late promoters. As a result, cells with
      defective TSG101 fail to express late viral proteins, leading to a decrease in
      the yield of virus particles. Thus, the contribution of TSG101 to Rta-mediated
      late gene activation is of great importance for completion of the EBV productive
      lytic cycle. These observations consolidate a role for TSG101 in the replication
      of EBV, a DNA virus, that differs from what is observed for RNA viruses, where
      TSG101 aids mainly in the endosomal sorting of enveloped late viral proteins for
      assembly at the plasma membrane.

PMID- 17182692
TI  - Interaction of rotavirus polymerase VP1 with nonstructural protein NSP5 is
      stronger than that with NSP2.
AB  - Rotavirus morphogenesis starts in intracellular inclusion bodies called
      viroplasms. RNA replication and packaging are mediated by several viral proteins,
      of which VP1, the RNA-dependent RNA polymerase, and VP2, the core scaffolding
      protein, were shown to be sufficient to provide replicase activity in vitro. In
      vivo, however, viral replication complexes also contain the nonstructural
      proteins NSP2 and NSP5, which were shown to be essential for replication, to
      interact with each other, and to form viroplasm-like structures (VLS) when
      coexpressed in uninfected cells. In order to gain a better understanding of the
      intermediates formed during viral replication, this work focused on the
      interactions of NSP5 with VP1, VP2, and NSP2. We demonstrated a strong
      interaction of VP1 with NSP5 but only a weak one with NSP2 in cotransfected cells
      in the absence of other viral proteins or viral RNA. By contrast, we failed to
      coimmunoprecipitate VP2 with anti-NSP5 antibodies or NSP5 with anti-VP2
      antibodies. We constructed a tagged form of VP1, which was found to colocalize in
      viroplasms and in VLS formed by NSP5 and NSP2. The tagged VP1 was able to replace
      VP1 structurally by being incorporated into progeny viral particles. When
      applying anti-tag-VP1 or anti-NSP5 antibodies, coimmunoprecipitation of tagged
      VP1 with NSP5 was found. Using deletion mutants of NSP5 or different fragments of
      NSP5 fused to enhanced green fluorescent protein, we identified the 48 C-terminal
      amino acids as the region essential for interaction with VP1.

PMID- 17182693
TI  - Inhibition of filovirus replication by the zinc finger antiviral protein.
AB  - The zinc finger antiviral protein (ZAP) was recently shown to inhibit Moloney
      murine leukemia virus and Sindbis virus replication. We tested whether ZAP also
      acts against Ebola virus (EBOV) and Marburg virus (MARV). Antiviral effects were
      observed after infection of cells expressing the N-terminal part of ZAP fused to
      the product of the zeocin resistance gene (NZAP-Zeo) as well as after infection
      of cells inducibly expressing full-length ZAP. EBOV was inhibited by up to 4 log
      units, whereas MARV was inhibited between 1 to 2 log units. The activity of ZAP
      was dependent on the integrity of the second and fourth zinc finger motif, as
      tested with cell lines expressing NZAP-Zeo mutants. Heterologous expression of
      EBOV- and MARV-specific sequences fused to a reporter gene suggest that ZAP
      specifically targets L gene sequences. The activity of NZAP-Zeo in this assay was
      also dependent on the integrity of the second and fourth zinc finger motif. Time
      course experiments with infectious EBOV showed that ZAP reduces the level of L
      mRNA before the level of genomic or antigenomic RNA is affected. Transient
      expression of ZAP decreased the activity of an EBOV replicon system by up to 95%.
      This inhibitory effect could be partially compensated for by overexpression of L
      protein. In conclusion, the data demonstrate that ZAP exhibits antiviral activity
      against filoviruses, presumably by decreasing the level of viral mRNA.

PMID- 17182694
TI  - Cytosolic prion protein toxicity is independent of cellular prion protein
      expression and prion propagation.
AB  - Prion diseases are transmissible neurodegenerative diseases caused by a
      conformational isoform of the prion protein (PrP), a host-encoded cell surface
      sialoglycoprotein. Recent evidence suggests a cytosolic fraction of PrP (cyPrP)
      functions either as an initiating factor or toxic element of prion disease. When
      expressed in cultured cells, cyPrP acquires properties of the infectious
      conformation of PrP (PrP(Sc)), including insolubility, protease resistance,
      aggregation, and toxicity. Transgenic mice (2D1 and 1D4 lines) that coexpress
      cyPrP and PrP(C) exhibit focal cerebellar atrophy, scratching behavior, and gait
      abnormalities suggestive of prion disease, although they lack protease-resistant
      PrP. To determine if the coexpression of PrP(C) is necessary or inhibitory to the
      phenotype of these mice, we crossed Tg1D4(Prnp(+/+)) mice with PrP-ablated mice
      (TgPrnp(o/o)) to generate Tg1D4(Prnp(o/o)) mice and followed the development of
      disease and pathological phenotype. We found no difference in the onset of
      symptoms or the clinical or pathological phenotype of disease between
      Tg1D4(Prnp(+/+)) and Tg1D4(Prnp(o/o)) mice, suggesting that cyPrP and PrP(C)
      function independently in the disease state. Additionally, Tg1D4(Prnp(o/o)) mice
      were resistant to challenge with mouse-adapted scrapie (RML), suggesting cyPrP is
      inaccessible to PrP(Sc). We conclude that disease phenotype and cellular toxicity
      associated with the expression of cyPrP are independent of PrP(C) and the
      generation of typical prion disease.

PMID- 17182695
TI  - Declining growth rate of West Nile virus in North America.
AB  - To determine the demographic history of West Nile virus (WNV) in North America,
      we employed a coalescent method to envelope coding region data sets for the NY99
      and WN02 genotypes. Although the observed genetic diversities in both genotypes
      were of approximately the same age, the mean rate of epidemiological growth of
      the WN02 population was approximately three times that of the NY99 population, a
      finding compatible with the recent dominance of the former genotype. However,
      there has also been a marked decrease in the recent growth rate of WN02,
      suggesting that WNV has reached its peak prevalence in North America.

PMID- 17182696
TI  - Dendritic cell-mediated trans-enhancement of human immunodeficiency virus type 1
      infectivity is independent of DC-SIGN.
AB  - Dendritic cells (DCs) enhance human immunodeficiency virus type 1 (HIV-1)
      infection of CD4(+) T lymphocytes in trans. The C-type lectin DC-SIGN, expressed
      on DCs, binds to the HIV-1 envelope glycoprotein gp120 and confers upon some cell
      lines the capacity to enhance trans-infection. Using a short hairpin RNA
      approach, we demonstrate that DC-SIGN is not required for efficient trans
      enhancement by DCs. In addition, the DC-SIGN ligand mannan and an anti-DC-SIGN
      antibody did not inhibit DC-mediated enhancement. HIV-1 particles were
      internalized and were protected from protease treatment following binding to DCs,
      but not from binding to DC-SIGN-expressing Raji cells. Thus, DC-SIGN is not
      required for DC-mediated trans-enhancement of HIV infectivity.

PMID- 17182697
TI  - Enrichment or depletion of a GO category within a class of genes: which test?
AB  - MOTIVATION: A number of available program packages determine the significant
      enrichments and/or depletions of GO categories among a class of genes of
      interest. Whereas a correct formulation of the problem leads to a single exact
      null distribution, these GO tools use a large variety of statistical tests whose
      denominations often do not clarify the underlying P-value computations. SUMMARY:
      We review the different formulations of the problem and the tests they lead to:
      the binomial, chi2, equality of two probabilities, Fisher's exact and
      hypergeometric tests. We clarify the relationships existing between these tests,
      in particular the equivalence between the hypergeometric test and Fisher's exact
      test. We recall that the other tests are valid only for large samples, the test
      of equality of two probabilities and the chi2-test being equivalent. We discuss
      the appropriateness of one- and two-sided P-values, as well as some discreteness
      and conservatism issues. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 17182698
TI  - Robust prediction of consensus secondary structures using averaged base pairing
      probability matrices.
AB  - MOTIVATION: Recent transcriptomic studies have revealed the existence of a
      considerable number of non-protein-coding RNA transcripts in higher eukaryotic
      cells. To investigate the functional roles of these transcripts, it is of great
      interest to find conserved secondary structures from multiple alignments on a
      genomic scale. Since multiple alignments are often created using alignment
      programs that neglect the special conservation patterns of RNA secondary
      structures for computational efficiency, alignment failures can cause potential
      risks of overlooking conserved stem structures. RESULTS: We investigated the
      dependence of the accuracy of secondary structure prediction on the quality of
      alignments. We compared three algorithms that maximize the expected accuracy of
      secondary structures as well as other frequently used algorithms. We found that
      one of our algorithms, called McCaskill-MEA, was more robust against alignment
      failures than others. The McCaskill-MEA method first computes the base pairing
      probability matrices for all the sequences in the alignment and then obtains the
      base pairing probability matrix of the alignment by averaging over these
      matrices. The consensus secondary structure is predicted from this matrix such
      that the expected accuracy of the prediction is maximized. We show that the
      McCaskill-MEA method performs better than other methods, particularly when the
      alignment quality is low and when the alignment consists of many sequences. Our
      model has a parameter that controls the sensitivity and specificity of
      predictions. We discussed the uses of that parameter for multi-step screening
      procedures to search for conserved secondary structures and for assigning
      confidence values to the predicted base pairs. AVAILABILITY: The C++ source code
      that implements the McCaskill-MEA algorithm and the test dataset used in this
      paper are available at http://www.ncrna.org/papers/McCaskillMEA/. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17182699
TI  - URec: a system for unrooted reconciliation.
AB  - URec is a software based on a concept of unrooted reconciliation. It can be used
      to reconcile a set of unrooted gene trees with a rooted species tree or a set of
      rooted species trees. Moreover, it computes detailed distribution of gene
      duplications and gene losses in a species tree. It can be used to infer optimal
      species phylogenies for a given set of gene trees. URec is implemented in C++ and
      can be easily compiled under Unix and Windows systems. AVAILABILITY: Software is
      freely available for download from our website at
      http://bioputer.mimuw.edu.pl/~gorecki/urec. This webpage also contains Windows
      executables and a number of advanced examples with explanations.

PMID- 17182700
TI  - Clustering threshold gradient descent regularization: with applications to
      microarray studies.
AB  - MOTIVATION: An important goal of microarray studies is to discover genes that are
      associated with clinical outcomes, such as disease status and patient survival.
      While a typical experiment surveys gene expressions on a global scale, there may
      be only a small number of genes that have significant influence on a clinical
      outcome. Moreover, expression data have cluster structures and the genes within a
      cluster have correlated expressions and coordinated functions, but the effects of
      individual genes in the same cluster may be different. Accordingly, we seek to
      build statistical models with the following properties. First, the model is
      sparse in the sense that only a subset of the parameter vector is non-zero.
      Second, the cluster structures of gene expressions are properly accounted for.
      RESULTS: For gene expression data without pathway information, we divide genes
      into clusters using commonly used methods, such as K-means or hierarchical
      approaches. The optimal number of clusters is determined using the Gap statistic.
      We propose a clustering threshold gradient descent regularization (CTGDR) method,
      for simultaneous cluster selection and within cluster gene selection. We apply
      this method to binary classification and censored survival analysis. Compared to
      the standard TGDR and other regularization methods, the CTGDR takes into account
      the cluster structure and carries out feature selection at both the cluster level
      and within-cluster gene level. We demonstrate the CTGDR on two studies of cancer
      classification and two studies correlating survival of lymphoma patients with
      microarray expressions. AVAILABILITY: R code is available upon request.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 17182701
TI  - A plant mutase that interconverts UDP-arabinofuranose and UDP-arabinopyranose.
AB  - Plant cell walls constitute the bulk of the earth renewable source of energy and
      are a component in the diet of humans and herbivores. l-Arabinofuranosyl (Araf)
      residues are a quantifiably important constituent of these walls. Plants use
      uridine diphosphate (UDP)-l-arabinofuranose (UDP-Araf) to donate Araf residues in
      the biosynthesis of Araf-containing polysaccharides, proteoglycans, and
      glycoproteins. However, little is known about the formation of UDP-Araf. We now
      describe the purification and partial characterization of a rice UDP
      arabinopyranose mutase (UAM) that catalyzes the formation of UDP-Araf from UDP
      arabinopyranose (UDP-Arap). The reaction is reversible and at thermodynamic
      equilibrium the pyranose form is favored over the furanose form (90 : 10). Three
      related proteins that are encoded by rice gene loci Os03g40270, Os04g56520, and
      Os07g41360 were identified from partial amino acid sequences of UAM. These
      proteins have >80% sequence identity with polypeptides that are reversibly
      glycosylated in the presence of UDP-sugars. The rice mutase and two functionally
      active recombinant mutases were shown to be reversibly glycosylated in the
      presence of UDP-Glc. The cofactor, flavin-adenine-dinucleotide (FAD), is required
      for the catalytic activity of UDP-galactose mutases of prokaryotes, fungi, and
      protozoa. The plant mutases, which do not require a cofactor, must therefore have
      a different catalytic mechanism. Putative UAM-encoding genes are present in the
      green algae Chlamydomonas reinhardtii, the moss Physcomitrella patens, the
      gymnosperm Pinus taeda (loblolly pine), and in numerous dicots and monocots,
      indicating that UAMs are widespread in green plants.

PMID- 17182702
TI  - Prenatal screening for congenital heart disease: a moving proposal.

PMID- 17182703
TI  - Chronic constipation as a causative factor for development of varicocele in men:
      a prospective ultrasonographic study.
AB  - OBJECTIVE: The purpose of this study was to determine the role of chronic
      constipation in the etiopathogenesis of varicocele in men. METHODS: In this
      prospective study, group 1 included 25 male patients who had symptoms of chronic
      constipation for a mean duration +/- SD of 17.0 +/- 20.3 months (range, 3-96
      months), and group 2 included 26 male subjects without any symptoms associated
      with constipation. All subjects were evaluated by both physical examination and
      scrotal ultrasonography. For the plexus pampiniformis (PP) veins, a mean diameter
      exceeding 2 mm and reflux for more than 1 second were accepted as suggestive
      findings for varicocele, as described previously. RESULTS: Left varicocele was
      detected in 13 (52%) of the 25 patients in group 1 and in 5 (19%) of the 26
      subjects in group 2 (P = .02). The mean diameters of the left PP veins were 2.58
      +/- 0.97 mm (range, 1.2-4.3 mm) in group 1 and 1.71 +/- 0.53 mm (range, 1.0-3.0
      mm) in group 2 (P < .001). A significant difference was detected between the two
      groups for varicocele prevalence and the mean diameter of the left PP veins.
      CONCLUSIONS: Chronic constipation is a significant causative factor for the
      development of left varicocele, which may be attributable to the accompanying
      distention of the sigmoid colon and distal part of the descending colon, with
      resultant compression of the left testicular vein in the retroperitoneum.
      Therefore, we propose routine ultrasonographic examinations for the possible
      development of varicocele in men with chronic constipation.

PMID- 17182704
TI  - Diagnostic performance of a random versus lesion-directed biopsy of the prostate
      from transrectal ultrasound: results of a 5-year consecutive clinical study in 1
      institution in South Taiwan.
AB  - OBJECTIVE: The purpose of this study was to compare cancer detection rates of
      sonographically suspicious lesion-directed biopsies and random biopsies through
      transverse examination of prostate halves in 518 patients over 5 years. METHODS:
      From 1998 to 2002, 518 patients were referred for prostate biopsies because of
      either elevated prostate-specific antigen (PSA) levels or abnormal digital rectal
      examination findings. On the basis of transverse examination of prostate halves
      by transrectal ultrasound, we performed lesion-directed biopsy of 3 to 5 cores if
      morphologically suspicious lesions existed on sonography or random biopsy of 3
      cores if no obvious suspicious lesions existed. Biopsy specimens were put into 2
      labeled containers. Pathologic results were correlated with random and lesion
      directed guided locations. RESULTS: Nine-hundred fifty-nine results were obtained
      from 439 random and 520 lesion-directed biopsies in 518 patients. Cancer was
      detected in 207 patients (40.7%). Patients with cancer who had PSA levels of 10.0
      ng/mL or greater had higher proportions of bilateral cancer lesions than those
      with PSA levels of less than 10 ng/mL (P = 0.03). One hundred ten (25.1%) of 439
      normal-appearing halves taken by random biopsy were tumor-positive compared with
      200 (38.5 %) of 520 biopsies from halves with sonographically suspicious lesions.
      Regardless of having random or lesion-directed biopsies, patients with PSA levels
      of 10 ng/mL or greater had higher positive malignancy rates than those with PSA
      levels of less than 10.0 ng/mL (P < .001). In about 40 patients, a diagnosis was
      made by random biopsy from halves that were morphologically normal on sonography,
      not by lesion-directed biopsy from tumor-suspicious contralateral halves.
      CONCLUSIONS: Cancer detection rates of lesion-directed biopsies are superior to
      those of random biopsies regardless of PSA level.

PMID- 17182705
TI  - Value of 3-dimensional transrectal/transvaginal sonography in diagnosis of distal
      ureteral calculi.
AB  - OBJECTIVE: In a prospective study, the feasibility of 3-dimensional (3D)
      transrectal/transvaginal sonography in comparison with transabdominal sonography
      and intravenous urography (IVU) in identifying distal ureteral calculi was
      evaluated. METHODS: Sixty-two patients in the urologic clinic with clinical
      suspicion of distal ureteral calculi were included. The patients consisted of 44
      men and 18 women with a mean age +/- SD of 44 +/- 17 years. These patients
      underwent 3D transrectal/transvaginal sonography, transabdominal sonography with
      IVU, and, finally, ureterorenoscopy. RESULTS: Fifty-nine patients were confirmed
      to have distal ureteral calculi on the basis of urologic intervention
      (ureterorenoscopy). Three patients had a spontaneous stone passage immediately
      after imaging completion. The median size of the calculi was 3.7 +/- 2.00 mm.
      Transabdominal sonography detected 34 of the 62 patients with calculi
      (sensitivity, 55%). The median size of the calculi was calculated as 5.0 +/- 2.4
      mm. The examination time was 6.5 +/- 2.7 minutes. Intravenous urography detected
      44 of the 62 patients with ureterolithiasis (sensitivity, 71%). Herein, the
      median stone size was measured as 3.9 +/- 1.9 mm, and the examination time was 38
      +/- 17 minutes. The combination of transabdominal sonography and IVU in
      visualization of ureterolithiasis raised the sensitivity to 81% (50 of 62
      patients). Three-dimensional transrectal/transvaginal sonography showed
      ureterolithiasis in all 62 patients confirmed to have distal ureteral calculi
      (sensitivity and specificity, 100%). The median size of the calculi was
      calculated as 4.4 +/- 2.2 mm, and the examination took 1.9 +/- 0.6 minutes.
      CONCLUSIONS: The data in our prospective study show that transrectal/transvaginal
      sonography with 3D image assessment is superior to IVU and abdominal sonography
      for diagnosing distal ureteral calculi.

PMID- 17182706
TI  - Role of transcutaneous perianal ultrasonography in evaluation of fistulas in ano.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of transcutaneous
      perianal ultrasonography in evaluation of fistulas in ano and to assess its
      possible role as a first-line investigation, for follow-up, and as a possible
      substitute for magnetic resonance imaging. METHODS: Transcutaneous perianal
      ultrasonography was performed in 30 patients with fistulas in ano with the use of
      a 3- to 6-MHz sector probe, a 7- to 11-MHz linear probe, and a 5- to 7-MHz
      endocavitary probe. Patients were followed clinically and at surgery to assess
      the accuracy of transcutaneous perianal ultrasonography. RESULTS: A total of 43
      fistulas, sinus tracts, or both were found in 26 patients. They appeared as
      hypoechoic tracts. Eleven of 30 patients had the presence of a collection or
      abscess, which appeared as hypoechoic areas. Twenty-four of 29 patients with
      positive findings underwent surgery. In these, 35 of 39 tracts were surgically
      confirmed (positive predictive value, 90%). The positive predictive value for
      demonstration of an internal opening was 85% (22/26) when compared with direct
      visualization or probing. Sensitivity for detection of tracts was 100%, and that
      for demonstration of an internal opening was 96% (26/27). The negative predictive
      value for sinus/fistulous tracts was nearly 100%. Transcutaneous perianal
      ultrasonography could not adequately evaluate suprasphincteric-type fistulas.
      However, it is a good, inexpensive modality in the evaluation of patients with
      fistulas in ano and also helps in follow-up of these patients. It can also be
      used to select patients who need magnetic resonance imaging. CONCLUSIONS:
      Transcutaneous perianal ultrasonography has the potential to become the first
      investigation in patients with perianal fistulas and abscesses.

PMID- 17182707
TI  - Sonographic appearance of the normal appendix in adults.
AB  - OBJECTIVE: To evaluate the sonographic visualization of the normal adult
      appendix, a large series of sonographic images from consecutive asymptomatic
      patients was analyzed. METHODS: A total of 788 consecutive adult patients (402
      male and 386 female; median age +/- SD, 51.1 +/- 17.2 years; range, 16-91 years)
      were examined by appendiceal transabdominal sonography with tissue harmonic
      imaging. The detection rate, outer appendiceal diameter, intraluminal content,
      and location of the appendix were estimated. The overall normal appendix was
      separated into appendix-visualized and appendix-not-visualized groups, which were
      then examined for the relationship with abdominal wall thickness, body mass index
      (in kilograms per square meter), age, and sex. RESULTS: The normal appendix was
      detected in 388 (49.2%) of 788 patients. The outer appendiceal diameter +/- SD
      was 4.27 +/- 1.2 mm (range, 1.0-11.1 mm). In 291 (75%) of the 388 patients,
      appendices could be depicted in the intra-luminal gas during sonography. The
      location of the appendix was classified according to the appendiceal tip, which
      was found to be abdominal in 37 (9.5%), pelvic in 291 (75%), retrocecal in 23
      (6.0%), and a midline extension in 37 (9.5%). In both body mass index and
      abdominal wall thickness, significant differences were found between appendix
      visualized and appendix-not-visualized cases (P < .05). There was no significant
      difference in age (P = .37) or sex (P = .23) between appendix-visualized and
      appendix-not-visualized cases. CONCLUSIONS: The results show that the normal
      adult appendix can be revealed by sonographic visualization in a large series of
      asymptomatic patients.

PMID- 17182708
TI  - Sonographic differentiation of benign and malignant cystic lesions of the breast.
AB  - OBJECTIVE: The purpose of this study was to subdivide the types of sonographic
      findings of benign versus malignant cystic masses and to determine appropriate
      patient care according to the sonographic findings with pathologic correlation.
      METHODS: The sonographic findings of 175 symptomatic cystic breast lesions were
      pathologically proven and reviewed retrospectively. Cystic lesions were
      classified as 6 types: simple cysts (type I), clustered cysts (type II), cysts
      with thin septa (type III), complicated cysts (type IV), cystic masses with a
      thick wall/septa or nodules (type V), and complex solid and cystic masses (type
      VI). Sonographic findings were compared with the pathologic results and were
      evaluated according to the incidence of benign and malignant masses. RESULTS: All
      23 type I, 15 type II, 22 type III, and 35 type IV cases were pathologically
      proven to be benign. Seven (25.9%) of the 27 type V cases and 33 (62.3%) of the
      53 type VI cases were proven to be malignant. We analyzed the shapes and margins
      of 80 cases of cystic masses with a solid component (types V and VI); 16 (44%) of
      36 sonographically circumscribed masses were malignant. CONCLUSIONS: Because the
      sonographically detected simple cysts (type I), clustered cysts (type II), and
      cysts with thin septa (type III) were all benign, annual routine follow-up
      appears reasonable. Symptomatic complicated cysts (type IV) should be aspirated
      and appropriately treated according to clinical symptoms. Cystic masses with a
      solid component (types V and VI) should be examined by biopsy with pathologic
      confirmation.

PMID- 17182709
TI  - Sonographic evaluation of the endometrium in patients with a history or an
      appearance of polycystic ovarian syndrome.
AB  - OBJECTIVE: The purpose of this study was to assess the incidence and significance
      of a thick, cystic-appearing endometrium in association with a history or an
      ovarian appearance of polycystic ovarian syndrome. METHODS: An Institutional
      Review Board-approved, retrospective medical record review of sonographic studies
      from January 1, 1998, to December 31, 2005, found 245 patients with clinical
      features, a characteristic sonographic appearance of the ovaries, hormonal
      abnormalities, or a history of polycystic ovarian syndrome. The sonographic
      thickness and appearance of the endometrium (homogeneous or heterogeneous) and
      histologic findings on biopsy were obtained. RESULTS: Two hundred twenty-seven
      patients had a homogeneous endometrium in the range of 1 to 17 mm (mean +/- SD,
      6.4 +/- 3.1 mm); 18 patients had a heterogeneous endometrium in the range of 4 to
      23 mm (mean, 13.2 +/- 5.6 mm). Of the 18 patients with a heterogeneous
      endometrium, 9 also had a sonographic finding of tiny cystic foci within the
      endometrium. Of these, 5 had endometrial biopsy, resulting in 2 cases of a
      proliferative endometrium and 1 case each of simple hyperplasia, hyperplasia with
      atypia, and scant tissue. No cases of hyperplasia were present in the patients
      with a homogeneous endometrium. CONCLUSIONS: A heterogeneous cystic endometrium
      is associated with the prolonged proliferative phase from chronic anovulation as
      well as endometrial hyperplasia.

PMID- 17182710
TI  - Correlation of prenatal sonographic diagnosis and morphologic findings of fetal
      autopsy in fetuses with trisomy 21.
AB  - OBJECTIVE: The purpose of this study was to compare the prenatal sonographic and
      postmortem pathologic findings of fetuses with trisomy 21. METHODS: Among 22,150
      fetal chromosome analyses, trisomy 21 was diagnosed in 207 fetuses between 1990
      and 2004. Findings of second-trimester sonography and fetal autopsy were compared
      by organ system, and their correlation was assigned to 1 of 3 categories.
      RESULTS: In total, 83.1% of the 184 fetuses that constituted the final study
      group had 1 or more abnormal structural findings at postabortion pathologic
      examination, whereas in 16.9% of the cases, fetal pathologic examination did not
      reveal any defects in fetal anatomy. Among major structural defects, the
      agreement between sonographic and autopsy findings was greater than 60% of all
      abnormalities of these systems: central nervous system (65.4%), heart (67.4%),
      fetal hydrops (100%), and cystic hygroma (93.3%), whereas the concordance rate
      was lower in these organ systems: abdominal abnormalities (46.2%), renal
      anomalies (50%), facial abnormalities (1.2%), and extremities (4.4%). The rate of
      additional major findings at autopsy was 34.2%. These mainly involved 3 organ
      systems: heart, head, and abdominal anomalies. Some sonographic findings (n = 16)
      were not verified at autopsy. The concordances between sonographic and autopsy
      findings regarding soft markers were considerably high in these markers:
      increased nuchal fold thickness (72%), short femur/humerus (75%), and pyelectasis
      (51.9%). CONCLUSIONS: Examining the correlation between sonography and pathologic
      findings may indicate possible directions of further development in sonographic
      screening for trisomy 21. In addition to obstetricians, pediatricians, and
      geneticists, specialized perinatal pathologists have an important role in the
      multidisciplinary management of prenatally diagnosed fetal malformations.

PMID- 17182711
TI  - An increased thermal index can be achieved when performing Doppler studies in
      obstetric sonography.
AB  - OBJECTIVE: The present study was aimed at evaluating acoustic outputs during
      clinical ultrasound examinations, as expressed by the thermal index (TI) and the
      mechanical index (MI), during the second half of pregnancy and comparing acoustic
      outputs between B-mode and Doppler examinations. METHODS: Patients with suspected
      fetal growth problems undergoing Doppler studies of the fetal circulation in
      addition to B-mode sonography were selected. Examinations took place between 21
      and 40 weeks' gestation. An obstetrician collected data prospectively.
      Sonographers were unaware of the data being sought. The analysis of variance test
      was applied for differences in continuous variables. RESULTS: A total of 63
      examinations were evaluated. The mean gestational age +/- SD was 31.6 +/- 5.1
      weeks. The mean duration of the total examinations was 17.6 +/- 8.6 minutes,
      whereas the Doppler studies lasted 0.9 +/- 0.8 minutes. The TI was significantly
      higher in the pulsed wave Doppler studies (mean, 1.5 +/- 0.5; range, 0.9-2.8) and
      color flow imaging studies (mean, 0.8 +/- 0.1; range, 0.6-1.2) compared with B
      mode sonography (mean, 0.3 +/- 0.1; range, 0.1-0.7; P < .01). During the
      examination, 190 B-mode MI variations were recorded (mean, 1.1 +/- 0.1), which
      were comparable with those of the 31 color flow Doppler studies (mean, 1.0 +/-
      0.1; P = .09) but higher than the 190 pulsed wave Doppler MI variations (mean 0.9
      +/- 0.2; P < .001). CONCLUSIONS: Increased acoustic output levels, as expressed
      by TI levels, are reached during obstetric Doppler studies. In particular, TI
      levels may reach 1.5 and higher. Doppler procedures should be performed with
      caution and be as brief as possible during obstetric sonography.

PMID- 17182712
TI  - Sonographic features of female pelvic tuberculous peritonitis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the sonographic features of
      tuberculous peritonitis in an attempt to facilitate the recognition of this
      disorder preoperatively. METHODS: The sonographic findings of 16 patients who had
      tuberculous peritonitis were reviewed. RESULTS: The sonographic findings showed
      that 14 of the 16 patients had ascites; 10 of these had fine, complete and
      incomplete mobile septations. Of these 10 patients, 4 had ascites with a
      latticelike appearance, and 2 had ascites with a parallel violin string
      appearance, which to our knowledge has not been described previously; 3 had
      particulate ascites. Peritoneal and omental thickening or nodules were identified
      in 9 patients. Two patients showed bilateral complex adnexal masses with
      multiloculated fluid with a thick wall-like tubo-ovarian abscess. CONCLUSIONS:
      Tuberculous peritonitis seems to have characteristic sonographic features,
      especially the findings of peritoneal and omental thickening and ascites with
      fine, mobile septations. These sonographic findings may provide valuable
      information to help with further investigations and may prevent unnecessary
      laparotomies.

PMID- 17182713
TI  - The cisterna magna septa: vestigial remnants of Blake's pouch and a potential new
      marker for normal development of the rhombencephalon.
AB  - OBJECTIVE: The purpose of this study was to show the normal sonographic
      embryologic anatomy of the cisterna magna septa, fourth ventricle, and cerebellar
      vallecula at various stages of development and our experience with their variable
      appearance in multiple planes and to discuss the probable relationship between
      the cisterna magna septa, Dandy-Walker continuum, mega cisterna magna, and
      persistent Blake's pouch. METHODS: Retrospective and prospective selection of
      examples of cisterna magna septa was performed over approximately a 12-month
      period. Standard and nonstandard imaging planes were adopted as necessary.
      RESULTS: The septa are typically seen inferoposterior to the cerebellar vermis,
      usually straight and parallel, arising at the cerebellovermian angle and coursing
      posteriorly to the occipital bone. The cisterna magna septa become contiguous
      with the roof of the fourth ventricle inferior to the cerebellar vermis. The
      cerebrospinal fluid space enclosed between the cisterna magna septa is in direct
      contiguity with the fourth ventricle via the vallecula and is always completely
      anechoic because it develops intra- and not extra-axially. CONCLUSIONS: We
      propose that the cisterna magna septa represent the walls of Blake's pouch, a
      phylogenetic vestigial structure observed during ontogeny. Additionally, our
      observations support current opinion that a persistent Blake's pouch and mega
      cisterna magna represent (less severe) abnormalities within the Dandy-Walker
      continuum. The cisterna magna septa therefore are a marker of normal development
      of the roof of the rhombencephalon. Deviation from their normal appearances
      should prompt a closer assessment for associated abnormalities of the cerebellum,
      vermis, and brain stem by additional imaging in orthogonal planes with either
      sonography or magnetic resonance imaging.

PMID- 17182714
TI  - Dizygotic twin pregnancy discordant for sirenomelia.

PMID- 17182715
TI  - Four-dimensional ultrasonographic guidance of fetal tracheal occlusion in a
      congenital diaphragmatic hernia.

PMID- 17182716
TI  - Torsion of the appendix secondary to appendiceal mucocele: gray scale and
      contrast-enhanced sonographic findings.

PMID- 17182717
TI  - Gastrointestinal stromal tumor presenting as a mass on pelvic sonography.

PMID- 17182718
TI  - Primary small-bowel melanoma: color Doppler ultrasonographic, computed
      tomographic, and radiologic findings with pathologic correlations.

PMID- 17182719
TI  - Sparganosis in the scrotum: sonographic findings.

PMID- 17182720
TI  - Fibrous pseudotumor of the scrotum.

PMID- 17182721
TI  - Sonographic features of a spermatic cord capillary hemangioma.

PMID- 17182722
TI  - Sonographic and magnetic resonance imaging appearance of a burned-out testicular
      germ cell neoplasm.

PMID- 17182723
TI  - Cyst of the canal of Nuck.

PMID- 17182724
TI  - Non-invasive anatomical and functional imaging for the detection of coronary
      artery disease.
AB  - Coronary artery disease (CAD) is still an important cause of morbidity and
      mortality in the Western world. The gold standard for assessing significant
      coronary artery stenosis is invasive coronary angiography. Several disadvantages
      of the technique in combination with the fact that a substantial number of
      patients referred for conventional angiography appear free from significant
      stenosis have led to the pursuit of non-invasive imaging modalities for the
      diagnosis of CAD. The traditional modalities for this purpose are gated single
      photon emission computed tomography, position emission tomography, (contrast)
      stress echocardiography and cardiac magnetic resonance (CMR), and these
      techniques can be characterized as functional imaging techniques as they detect
      ischaemia. Although the presence of a flow-limiting stenosis can be adequately
      ruled out with these techniques, atherosclerosis cannot be visualized with
      functional techniques. For this purpose, non-invasive coronary angiography
      techniques (computed tomography and CMR) are currently under development. The
      purpose of this review is to provide the reader an overview of the currently used
      imaging modalities to detect CAD.

PMID- 17182725
TI  - Pyruvate induces mitochondrial biogenesis by a PGC-1 alpha-independent mechanism.
AB  - Oxidative cells increase mitochondrial mass in response to stimuli such as
      changes in energy demand or cellular differentiation. This plasticity enables the
      cell to adapt dynamically to achieve the necessary oxidative capacity. However,
      the pathways involved in triggering mitochondrial biogenesis are poorly defined.
      The present study examines the impact of altering energy provision on
      mitochondrial biogenesis in muscle cells. C2C12 myoblasts were chronically
      treated with supraphysiological levels of sodium pyruvate for 72 h. Treated cells
      exhibited increased mitochondrial protein expression, basal respiratory rate, and
      maximal oxidative capacity. The increase in mitochondrial biogenesis was
      independent of increases in peroxisomal proliferator activator receptor-gamma
      coactivator-1alpha (PGC-1alpha) and PGC-1beta mRNA expression. To further assess
      whether PGC-1alpha expression was necessary for pyruvate action, cells were
      infected with adenovirus containing shRNA for PGC-1alpha before treatment with
      pyruvate. Despite a 70% reduction in PGC-1alpha mRNA, the effect of pyruvate was
      preserved. Furthermore, pyruvate induced mitochondrial biogenesis in primary
      myoblasts from PGC-1alpha null mice. These data suggest that regulation of
      mitochondrial biogenesis by pyruvate in myoblasts is independent of PGC-1alpha,
      suggesting the existence of a novel energy-sensing pathway regulating oxidative
      capacity.

PMID- 17182726
TI  - Elevated resting [Ca(2+)](i) in myotubes expressing malignant hyperthermia RyR1
      cDNAs is partially restored by modulation of passive calcium leak from the SR.
AB  - Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle
      triggered in susceptible individuals by inhalation anesthetics and depolarizing
      skeletal muscle relaxants. This syndrome has been linked to a missense mutation
      in the type 1 ryanodine receptor (RyR1) in more than 50% of cases studied to
      date. Using double-barreled Ca(2+) microelectrodes in myotubes expressing wild
      type RyR1 ((WT)RyR1) or RyR1 with one of four common MH mutations ((MH)RyR1), we
      measured resting intracellular Ca(2+) concentration ([Ca(2+)](i)). Changes in
      resting [Ca(2+)](i) produced by several drugs known to modulate the RyR1 channel
      complex were investigated. We found that myotubes expressing any of the (MH)RyR1s
      had a 2.0- to 3.7-fold higher resting [Ca(2+)](i) than those expressing (WT)RyR1.
      Exposure of myotubes expressing (MH)RyR1s to ryanodine (500 microM) or (2,6
      dichloro-4-aminophenyl)isopropylamine (FLA 365; 20 microM) had no effects on
      their resting [Ca(2+)](i). However, when myotubes were exposed to bastadin 5
      alone or to a combination of ryanodine and bastadin 5, the resting [Ca(2+)](i)
      was significantly reduced (P < 0.01). Interestingly, the percent decrease in
      resting [Ca(2+)](i) in myotubes expressing (MH)RyR1s was significantly greater
      than that for (WT)RyR1. From these data, we propose that the high resting
      myoplasmic [Ca(2+)](i) in (MH)RyR1 expressing myotubes is due in part to a
      related structural conformation of (MH)RyR1s that favors "passive" calcium leak
      from the sarcoplasmic reticulum.

PMID- 17182727
TI  - Altered pH(i) regulation and Na(+)/HCO3(-) transporter activity in choroid plexus
      of cilia-defective Tg737(orpk) mutant mouse.
AB  - Tg737(orpk) mice have defects in cilia assembly and develop hydrocephalus in the
      perinatal period of life. Hydrocephalus is progressive and is thought to be
      initiated by abnormal ion and water transport across the choroid plexus
      epithelium. The pathology is further aggravated by the slow and disorganized
      beating of motile cilia on ependymal cells that contribute to decreased
      cerebrospinal fluid movement through the ventricles. Previously, we demonstrated
      that the hydrocephalus phenotype is associated with a marked increase in
      intracellular cAMP levels in choroid plexus epithelium, which is known to have
      regulatory effects on ion and fluid movement in many secretory epithelia. To
      evaluate whether the hydrocephalus in Tg737(orpk) mutants is associated with
      defects in ion transport, we compared the steady-state pH(i) and Na(+)-dependent
      transport activities of isolated choroid plexus epithelium tissue from
      Tg737(orpk) mutant and wild-type mice. The data indicate that Tg737(orpk) mutant
      choroid plexus epithelium have lower pH(i) and higher Na(+)-dependent HCO(3)(-)
      transport activity compared with wild-type choroid plexus epithelium. In
      addition, wild-type choroid plexus epithelium could be converted to a mutant
      phenotype with regard to the activity of Na(+)-dependent HCO(3)(-) transport by
      addition of dibutyryl-cAMP and mutant choroid plexus epithelium toward the wild
      type phenotype by inhibiting PKA activity with H-89. Together, these data suggest
      that cilia have an important role in regulating normal physiology of choroid
      plexus epithelium and that ciliary dysfunction in Tg737(orpk) mutants disrupts a
      signaling pathway leading to elevated intracellular cAMP levels and aberrant
      regulation of pH(i) and ion transport activity.

PMID- 17182728
TI  - Differential localization of autolyzed calpains 1 and 2 in slow and fast skeletal
      muscles in the early phase of atrophy.
AB  - Calpains have been proposed to be involved in the cytoskeletal remodeling and
      wasting of skeletal muscle. However, limited data are available about the
      specific involvement of each calpain in the early stages of muscle atrophy. The
      aims of this study were to determine whether calpains 1 and 2 are autolyzed after
      a short period of muscle disuse, and, if so, where in the myofibers the autolyzed
      products are localized. In the rat soleus muscle, 5 days of immobilization
      increased autolyzed calpain 1 in the particulate and not the soluble fraction.
      Conversely, autolyzed calpain 2 was not found in the particulate fraction,
      whereas it was increased in the soluble fraction after immobilization. In the
      less atrophied plantaris muscle, no difference was noted between the control and
      immobilized groups whatever the fraction or calpain. Other proteolytic pathways
      were also investigated. The ubiquitin-proteasome pathway was activated in both
      skeletal muscles, and caspase 3 was activated only in the soleus muscle. Taken
      together, our data suggest that calpains 1 and 2 are involved in atrophy
      development in slow type muscle exclusively and that they have different
      regulation and protein targets. Moreover, the activation of proteolytic pathways
      appears to differ in slow and fast muscles, and the proteolytic mechanisms
      involved in fast-type muscle atrophy remain unclear.

PMID- 17182729
TI  - Role(s) of nucleoli and phosphorylation of ribosomal protein S6 and/or HSP27 in
      the regulation of muscle mass.
AB  - Effects of 14 days of hindlimb unloading or synergist ablation-related
      overloading with or without deafferentation on the fiber cross-sectional area,
      myonuclear number, size, and domain, the number of nucleoli in a single
      myonucleus, and the levels in the phosphorylation of the ribosomal protein S6
      (S6) and 27-kDa heat shock protein (HSP27) were studied in rat soleus.
      Hypertrophy of fibers (+24%), associated with increased nucleolar number (from 1
      2 to 3-5) within a myonucleus and myonuclear domain (+27%) compared with the
      preexperimental level, was induced by synergist ablation. Such phenomena were
      associated with increased levels of phosphorylated S6 (+84%) and HSP27 (+28%).
      Fiber atrophy (-52%), associated with decreased number (-31%) and domain size (
      28%) of myonuclei and phosphorylation of S6 (-98%) and HSP27 (-63%), and with
      increased myonuclear size (+19%) and ubiquitination of myosin heavy chain (+33%,
      P > 0.05), was observed after unloading, which inhibited the mechanical load.
      Responses to deafferentation, which inhibited electromyogram level (-47%), were
      basically similar to those caused by hindlimb unloading, although the magnitudes
      were minor. The deafferentation-related responses were prevented and nucleolar
      number was even increased (+18%) by addition of synergist ablation, even though
      the integrated electromyogram level was still 30% less than controls. It is
      suggested that the load-dependent maintenance or upregulation of the nucleolar
      number and/or phosphorylation of S6 and HSP27 plays the important role(s) in the
      regulation of muscle mass. It was also indicated that such regulation was not
      necessarily associated with the neural activity.

PMID- 17182730
TI  - Mass spectrometric identification of phosphorylation sites of rRNA transcription
      factor upstream binding factor.
AB  - rRNA transcription is a fundamental requirement for all cellular growth processes
      and is activated by the phosphorylation of the upstream binding factor (UBF) in
      response to growth stimulation. Even though it is well known that phosphorylation
      of UBF is required for its activation and is a key step in activation of rRNA
      transcription, as yet, there has been no direct mapping of the UBF
      phosphorylation sites. The results of the present studies employed sophisticated
      nano-flow HPLC-microelectrospray-ionization tandem mass spectrometry (nHPLC-muESI
      MS/MS) coupled with immobilized metal affinity chromatography (IMAC) and computer
      database searching algorithms to identify 10 phosphorylation sites on UBF at
      serines 273, 336, 364, 389, 412, 433, 484, 546, 584, and 638. We then carried out
      functional analysis of two of these sites, serines 389 and 584. Serine-alanine
      substitution mutations of 389 (S389A) abrogated rRNA transcription in vitro and
      in vivo, whereas mutation of serine 584 (S584A) reduced transcription in vivo but
      not in vitro. In contrast, serine-glutamate mutation of 389 (S389E) restored
      transcriptional activity. Moreover, S389A abolished UBF-SL1 interaction in vitro,
      while S389E partially restored UBF-SL1 interaction. Taken together, the results
      of these studies suggest that growth factor stimulation induces an increase in
      rRNA transcriptional activity via phosphorylation of UBF at serine 389 in part by
      facilitating a rate-limiting step in the recruitment of RNA polymerase I: i.e.,
      recruitment of SL1. Moreover, studies provide critical new data regarding
      multiple additional UBF phosphorylation sites that will require further
      characterization by the field.

PMID- 17182731
TI  - Regulatory interactions of N1303K-CFTR and ENaC in Xenopus oocytes: evidence that
      chloride transport is not necessary for inhibition of ENaC.
AB  - Regulatory interactions of the cystic fibrosis transmembrane conductance
      regulator (CFTR) and the epithelial Na(+) channel (ENaC) are readily apparent in
      Xenopus oocytes. However, the mechanism underlying these interactions remains
      controversial. CFTR's first nucleotide binding fold (NBD-1) may be important in
      these interactions, as dysfunctional CFTRs containing mutations within NBD-1,
      such as DeltaF508 and G551D, lack such functional interactions with murine ENaC
      (mENaC). We hypothesized that a dysfunctional CFTR containing a non-NBD-1
      mutation would retain regulatory interactions with mENaC and tested this
      hypothesis for N1303K-CFTR, where the mutation is located in CFTR's second
      nucleotide binding fold (NBD-2). cRNA for alphabetagamma-mENaC and N1303K-CFTR
      was injected separately or together into Xenopus oocytes. ENaC and CFTR
      functional expression was assessed by two-electrode voltage clamp. Injection of
      N1303K (class II trafficking mutation) yielded low levels of CFTR function on
      activation with forskolin and 3-isobutyl-1-methylxanthine (IBMX). In coinjected
      oocytes, N1303K did not alter mENaC functional expression or surface expression
      before activation of N1303K. This is similar to our prior observations with
      DeltaF508. However, unlike our observations with DeltaF508, activation of N1303K
      acutely decreased mENaC functional and surface expression, and N1303K currents
      were enhanced by coinjection of mENaC. Furthermore, genistein only mildly
      enhanced the functional expression of N1303K-CFTR and did not improve regulation
      of ENaC by N1303K-CFTR. These data suggest that a structurally and functionally
      intact CFTR NBD-1 in activated CFTR can regulate mENaC surface expression
      independent of Cl(-) transport in Xenopus oocytes.

PMID- 17182732
TI  - Toothpicks, serendipity and the emergence of the Escherichia coli DnaK (Hsp70)
      and GroEL (Hsp60) chaperone machines.

PMID- 17182733
TI  - Approximate genealogies under genetic hitchhiking.
AB  - The rapid fixation of an advantageous allele leads to a reduction in linked
      neutral variation around the target of selection. The genealogy at a neutral
      locus in such a selective sweep can be simulated by first generating a random
      path of the advantageous allele's frequency and then a structured coalescent in
      this background. Usually the frequency path is approximated by a logistic growth
      curve. We discuss an alternative method that approximates the genealogy by a
      random binary splitting tree, a so-called Yule tree that does not require first
      constructing a frequency path. Compared to the coalescent in a logistic
      background, this method gives a slightly better approximation for identity by
      descent during the selective phase and a much better approximation for the number
      of lineages that stem from the founder of the selective sweep. In applications
      such as the approximation of the distribution of Tajima's D, the two
      approximation methods perform equally well. For relevant parameter ranges, the
      Yule approximation is faster.

PMID- 17182734
TI  - The power stroke of myosin VI and the basis of reverse directionality.
AB  - Myosin VI supports movement toward the (-) end of actin filaments, despite
      sharing extensive sequence and structural homology with (+)-end-directed myosins.
      A class-specific stretch of amino acids inserted between the converter domain and
      the lever arm was proposed to provide the structural basis of directionality
      reversal. Indeed, the unique insert mediates a 120 degrees redirection of the
      lever arm in a crystal structure of the presumed poststroke conformation of
      myosin VI [Menetrey J, Bahloul A, Wells AL, Yengo CM, Morris CA, Sweeney HL,
      Houdusse A (2005) Nature 435:779-785]. However, this redirection alone is
      insufficient to account for the large (-)-end-directed stroke of a monomeric
      myosin VI construct. The underlying motion of the myosin VI converter domain must
      therefore differ substantially from the power stroke of (+)-end-directed myosins.
      To experimentally map out the motion of the converter domain and lever arm, we
      have generated a series of truncated myosin VI constructs and characterized the
      size and direction of the power stroke for each construct using dual-labeled
      gliding filament assays and optical trapping. Motors truncated near the end of
      the converter domain generate (+)-end-directed motion, whereas longer constructs
      move toward the (-) end. Our results directly demonstrate that the unique insert
      is required for directionality reversal, ruling out a large class of models in
      which the converter domain moves toward the (-) end. We suggest that the lever
      arm rotates approximately 180 degrees between pre- and poststroke conformations.

PMID- 17182735
TI  - The 1',4'-iminopyrimidine tautomer of thiamin diphosphate is poised for catalysis
      in asymmetric active centers on enzymes.
AB  - Thiamin diphosphate, a key coenzyme in sugar metabolism, is comprised of the
      thiazolium and 4'-aminopyrimidine aromatic rings, but only recently has
      participation of the 4'-aminopyrimidine moiety in catalysis gained wider
      acceptance. We report the use of electronic spectroscopy to identify the various
      tautomeric forms of the 4'-aminopyrimidine ring on four thiamin diphosphate
      enzymes, all of which decarboxylate pyruvate: the E1 component of human pyruvate
      dehydrogenase complex, the E1 subunit of Escherichia coli pyruvate dehydrogenase
      complex, yeast pyruvate decarboxylase, and pyruvate oxidase from Lactobacillus
      plantarum. It is shown that, according to circular dichroism spectroscopy, both
      the 1',4'-iminopyrimidine and the 4'-aminopyrimidine tautomers coexist on the E1
      component of human pyruvate dehydrogenase complex and pyruvate oxidase. Because
      both tautomers are seen simultaneously, these two enzymes provide excellent
      evidence for nonidentical active centers (asymmetry) in solution in these
      multimeric enzymes. Asymmetry of active centers can also be induced upon addition
      of acetylphosphinate, an excellent electrostatic pyruvate mimic, which
      participates in an enzyme-catalyzed addition to form a stable adduct, resembling
      the common predecarboxylation thiamin-bound intermediate, which exists in its
      1',4'-iminopyrimidine form. The identification of the 1',4'-iminopyrimidine
      tautomer on four enzymes is almost certainly applicable to all thiamin
      diphosphate enzymes: this tautomer is the intramolecular trigger to generate the
      reactive ylide/carbene at the thiazolium C2 position in the first fundamental
      step of thiamin catalysis.

PMID- 17182736
TI  - A quantitative study of bioenergetics in skeletal muscle lacking carbonic
      anhydrase III using 31P magnetic resonance spectroscopy.
AB  - Oxidative slow skeletal muscle contains carbonic anhydrase III in high
      concentration, but its primary function remains unknown. To determine whether its
      lack handicaps energy metabolism and/or acid elimination, we measured the
      intracellular pH and energy phosphates by (31)P magnetic resonance spectroscopy
      in hind limb muscles of wild-type and CA III knockout mice during and after
      ischemia and intense exercise (electrical stimulation). Thirty minutes of
      ischemia caused phosphocreatine (PCr) to fall and P(i) to rise while pH and ATP
      remained constant in both strains of mice. PCr and P(i) kinetics during ischemia
      and recovery were not significantly different between the two genotypes. From
      this we conclude that under neutral pH conditions resting muscle anaerobic
      metabolism, the rate of the creatine kinase reaction, intracellular buffering of
      protons, and phosphorylation of creatine by mitochondrial oxygen metabolism are
      not influenced by the lack of CA III. Two minutes of intense stimulation of the
      mouse gastrocnemius caused PCr, ATP, and pH to fall and ADP and P(i) to rise, and
      these changes, with the exception of ATP, were all significantly larger in the CA
      III knockouts. The rate of return of pH and ADP to control values was the same in
      wild-type and mutant mice, but in the mutants PCr and P(i) recovery were delayed
      in the first minute after stimulation. Because the tension decrease during
      fatigue is known to be the same in the two genotypes, we conclude that a lack of
      CA III impairs mitochondrial ATP synthesis.

PMID- 17182737
TI  - NMDA-dependent facilitation of corticostriatal plasticity by the amygdala.
AB  - Emotions generally improve memory, and the basolateral amygdala (BLA) is believed
      to mediate this effect. After emotional arousal, BLA neurons increase their
      firing rate, facilitating memory consolidation in BLA targets. The enhancing
      effects of BLA activity extend to various types of memories, including motor
      learning, which is thought to involve activity-dependent plasticity at
      corticostriatal synapses. However, the underlying mechanisms are unknown. Here we
      show that the NMDA-to-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid) ratio is nearly twice as high at BLA as compared with cortical synapses
      onto principal striatal neurons and that activation of BLA inputs greatly
      facilitates long-term potentiation induction at corticostriatal synapses. This
      facilitation was NMDA-dependent, but it occurred even when BLA and cortical
      stimuli were 0.5 s apart during long-term potentiation induction. Overall, these
      results suggest that BLA activity opens long time windows during which the
      induction of corticostriatal plasticity is facilitated.

PMID- 17182738
TI  - Monoalkyl sulfates as alkylating agents in water, alkylsulfatase rate
      enhancements, and the "energy-rich" nature of sulfate half-esters.
AB  - Alkyl sulfate monoesters are involved in cell signaling and structure. Alkyl
      sulfates are also present in many commercial detergents. Here, we show that
      monomethyl sulfate acts as an efficient alkylating agent in water, reacting
      spontaneously with oxygen nucleophiles >100-fold more rapidly than do
      alkylsulfonium ions, the usual methyl donors in living organisms. These reactions
      of methyl sulfate, which are much more rapid than its hydrolysis, are insensitive
      to the nature of the attacking nucleophile, with a Bronsted beta(nuc) value of 
      0.01. Experiments at elevated temperatures indicate a rate constant of 2 x 10(
      11) s(-1) for the uncatalyzed hydrolysis of methyl sulfate at 25 degrees C
      (t(1/2) = 1,100 y), corresponding to a rate enhancement of approximately 10(11)
      fold by a human alkylsulfatase. Equilibria of formation of methyl sulfate from
      methanol and sodium hydrogen sulfate indicate a group transfer potential
      (DeltaG'(pH7)) of -8.9 kcal/mol for sulfate ester hydrolysis. The magnitude of
      that value, involving release of the strong acid HSO(4)(-), helps to explain the
      need for harnessing the free energy of hydrolysis of two ATP molecules in
      activating sulfate for the biosynthesis of sulfate monoesters. The "energy-rich"
      nature of monoalkyl sulfate esters, coupled with their marked resistance to
      hydrolysis, renders them capable of acting as sulfating or alkylating agents
      under relatively mild conditions. These findings raise the possibility that,
      under appropriate circumstances, alkyl groups may undergo transfer from alkyl
      sulfate monoesters to biological target molecules.

PMID- 17182739
TI  - How personal experience modulates the neural circuitry of memories of September
      11.
AB  - Brown and Kulik [Brown R, Kulik J (1977) Cognition 5:73-99] introduced the term
      "flashbulb memory" to describe the recall of shocking, consequential events such
      as hearing news of a presidential assassination. They proposed that the vivid
      detail of such memories results from the action of a unique neural mechanism. In
      the present study of personal recollections of the terrorist attacks of September
      11, 2001 (9/11) in New York City, we combine behavioral and brain imaging
      techniques, with two goals: (i) to explore the neural basis of such memories and
      (ii) to clarify the characteristics of the emotional events that may give rise to
      them. Three years after the terrorist attacks, participants were asked to
      retrieve memories of 9/11, as well as memories of personally selected control
      events from 2001. At the time of the attacks, some participants were in Downtown
      Manhattan, close to the World Trade Center; others were in Midtown, a few miles
      away. The Downtown participants exhibited selective activation of the amygdala as
      they recalled events from 9/11, but not while they recalled control events. This
      was not the case for the Midtown participants. Moreover, only the Downtown
      participants reported emotionally enhanced recollective experiences while
      recalling events from 9/11, as compared with control events. These results
      suggest that close personal experience may be critical in engaging the neural
      mechanisms that underlie the emotional modulation of memory and thus in producing
      the vivid recollections to which the term flashbulb memory is often applied.

PMID- 17182740
TI  - Evidence for a chemical-thermal structure at base of mantle from sharp lateral P
      wave variations beneath Central America.
AB  - Compressional waves that sample the lowermost mantle west of Central America show
      a rapid change in travel times of up to 4 s over a sampling distance of 300 km
      and a change in waveforms. The differential travel times of the PKP waves (which
      traverse Earth's core) correlate remarkably well with predictions for S-wave
      tomography. Our modeling suggests a sharp transition in the lowermost mantle from
      a broad slow region to a broad fast region with a narrow zone of slowest anomaly
      next to the boundary beneath the Cocos Plate and the Caribbean Plate. The
      structure may be the result of ponding of ancient subducted Farallon slabs
      situated near the edge of a thermal and chemical upwelling.

PMID- 17182741
TI  - cAMP activation of PKA defines an ancient signaling mechanism.
AB  - cAMP and the cAMP binding domain (CBD) constitute a ubiquitous regulatory switch
      that translates an extracellular signal into a biological response. The CBD
      contains alpha- and beta-subdomains with cAMP binding to a phosphate binding
      cassette (PBC) in the beta-sandwich. The major receptors for cAMP in mammalian
      cells are the regulatory subunits (R-subunits) of PKA where cAMP and the
      catalytic subunit compete for the same CBD. The R-subunits inhibit kinase
      activity, whereas cAMP releases that inhibition. Here, we use NMR to map at
      residue resolution the cAMP-dependent interaction network of the CBD-A domain of
      isoform Ialpha of the R-subunit of PKA. Based on H/D, H/H, and N(z) exchange
      data, we propose a molecular model for the allosteric regulation of PKA by cAMP.
      According to our model, cAMP binding causes long-range perturbations that
      propagate well beyond the immediate surroundings of the PBC and involve two key
      relay sites located at the C terminus of beta(2) (I163) and N terminus of beta(3)
      (D170). The I163 site functions as one of the key triggers of global unfolding,
      whereas the D170 locus acts as an electrostatic switch that mediates the
      communication between the PBC and the B-helix. Removal of cAMP not only disrupts
      the cap for the B' helix within the PBC, but also breaks the circuitry of
      cooperative interactions stemming from the PBC, thereby uncoupling the alpha- and
      beta-subdomains. The proposed model defines a signaling mechanism, conserved in
      every genome, where allosteric binding of a small ligand disrupts a large protein
      protein interface.

PMID- 17182742
TI  - RecA-independent recombination is efficient but limited by exonucleases.
AB  - Genetic recombination in bacteria is facilitated by the RecA strand transfer
      protein and strongly depends on the homology between interacting sequences. RecA
      independent recombination is detectable but occurs at extremely low frequencies
      and is less responsive to the extent of homology. In this article, we show that
      RecA-independent recombination in Escherichia coli is depressed by the redundant
      action of single-strand exonucleases. In the absence of multiple single-strand
      exonucleases, the efficiency of RecA-independent recombination events, involving
      either gene conversion or crossing-over, is markedly increased to levels rivaling
      RecA-dependent events. This finding suggests that RecA-independent recombination
      is not intrinsically inefficient but is limited by single-strand DNA substrate
      availability. Crossing-over is inhibited by exonucleases ExoI, ExoVII, ExoX, and
      RecJ, whereas only ExoI and RecJ abort gene-conversion events. In ExoI(-) RecJ(-)
      strains, gene conversion can be accomplished by transformation of short single
      strand DNA oligonucleotides and is more efficient when the oligonucleotide is
      complementary to the lagging-strand replication template. We propose that E. coli
      encodes an unknown mechanism for RecA-independent recombination (independent of
      prophage recombination systems) that is targeted to replication forks. The
      potential of RecA-independent recombination to mediate exchange at short
      homologies suggests that it may contribute significantly to genomic change in
      bacteria, especially in species with reduced cellular exonuclease activity or
      those that encode DNA protection factors.

PMID- 17182743
TI  - Nitric oxide release combined with nonsteroidal antiinflammatory activity
      prevents muscular dystrophy pathology and enhances stem cell therapy.
AB  - Duchenne muscular dystrophy is a relatively common disease that affects skeletal
      muscle, leading to progressive paralysis and death. There is currently no
      resolutive therapy. We have developed a treatment in which we combined the
      effects of nitric oxide with nonsteroidal antiinflammatory activity by using HCT
      1026, a nitric oxide-releasing derivative of flurbiprofen. Here, we report the
      results of long-term (1-year) oral treatment with HCT 1026 of two murine models
      for limb girdle and Duchenne muscular dystrophies (alpha-sarcoglycan-null and mdx
      mice). In both models, HCT 1026 significantly ameliorated the morphological,
      biochemical, and functional phenotype in the absence of secondary effects,
      efficiently slowing down disease progression. HCT 1026 acted by reducing
      inflammation, preventing muscle damage, and preserving the number and function of
      satellite cells. HCT 1026 was significantly more effective than the
      corticosteroid prednisolone, which was analyzed in parallel. As an additional
      beneficial effect, HCT 1026 enhanced the therapeutic efficacy of arterially
      delivered donor stem cells, by increasing 4-fold their ability to migrate and
      reconstitute muscle fibers. The therapeutic strategy we propose is not selective
      for a subset of mutations; it provides ground for immediate clinical
      experimentation with HCT 1026 alone, which is approved for use in humans; and it
      sets the stage for combined therapies with donor or autologous, genetically
      corrected stem cells.

PMID- 17182744
TI  - Urban aerosols harbor diverse and dynamic bacterial populations.
AB  - Considering the importance of its potential implications for human health,
      agricultural productivity, and ecosystem stability, surprisingly little is known
      regarding the composition or dynamics of the atmosphere's microbial inhabitants.
      Using a custom high-density DNA microarray, we detected and monitored bacterial
      populations in two U.S. cities over 17 weeks. These urban aerosols contained at
      least 1,800 diverse bacterial types, a richness approaching that of some soil
      bacterial communities. We also reveal the consistent presence of bacterial
      families with pathogenic members including environmental relatives of select
      agents of bioterrorism significance. Finally, using multivariate regression
      techniques, we demonstrate that temporal and meteorological influences can be
      stronger factors than location in shaping the biological composition of the air
      we breathe.

PMID- 17182745
TI  - Maternal serotonin is crucial for murine embryonic development.
AB  - The early appearance of serotonin and its receptors during prenatal development,
      together with the many effects serotonin exerts during CNS morphogenesis,
      strongly suggest that serotonin influences the development and maturation of the
      mammalian brain before it becomes a neuromodulator/neurotransmitter. Sites of
      early serotonin biosynthesis, however, have not been detected in mouse embryos or
      extraembryonic structures, suggesting that the main source of serotonin could be
      of maternal origin. This hypothesis was tested by using knockout mice lacking the
      tph1 gene, which is responsible for the synthesis of peripheral serotonin.
      Genetic crosses were performed to compare the phenotype of pups born from
      homozygous and heterozygous mothers. Observations provide the first clear
      evidence that (i) maternal serotonin is involved in the control of morphogenesis
      during developmental stages that precede the appearance of serotonergic neurons
      and (ii) serotonin is critical for normal murine development. Most strikingly,
      the phenotype of tph1-/- embryos depends more on the maternal genotype than on
      that of the concepti. Consideration of the maternal genotype may thus help to
      clarify the influence of other genes in complex diseases, such as mental illness.

PMID- 17182746
TI  - Human Sco1 functional studies and pathological implications of the P174L mutant.
AB  - The pathogenic mutant (P174L) of human Sco1 produces respiratory chain deficiency
      associated with cytochrome c oxidase (CcO) assembly defects. The solution
      structure of the mutant in its Cu(I) form shows that Leu-174 prevents the
      formation of a well packed hydrophobic region around the metal-binding site and
      causes a reduction of the affinity of copper(I) for the protein. K(D) values for
      Cu(I)WT-HSco1 and Cu(I)P174L-HSco1 are approximately 10(-17) and approximately
      10(-13), respectively. The reduction potentials of the two apo proteins are
      similar, but slower reduction/oxidation rates are found for the mutant with
      respect to the WT. The mitochondrial metallochaperone in the partially oxidized
      Cu(1)(I)Cox17(2S-S) form, at variance with the fully reduced Cu(4)(I)Cox17,
      interacts transiently with both WT-HSco1 and the mutant, forming the
      Cox17/Cu(I)/HSco1 complex, but copper is efficiently transferred only in the case
      of WT protein. Cu(1)(I)Cox17(2S-S) indeed has an affinity for copper(I) (K(D)
      approximately 10(-15)) higher than that of the P174L-HSco1 mutant but lower than
      that of WT-HSco1. We propose that HSco1 mutation, altering the structure around
      the metal-binding site, affects both copper(I) binding and redox properties of
      the protein, thus impairing the efficiency of copper transfer to CcO. The
      pathogenic mutation therefore could (i) lessen the Sco1 affinity for copper(I)
      and hence copper supply for CcO or (ii) decrease the efficiency of reduction of
      CcO thiols involved in copper binding, or both effects could be produced by the
      mutation.

PMID- 17182747
TI  - Natural selection for rash-forming genotypes of the varicella-zoster vaccine
      virus detected within immunized human hosts.
AB  - The Oka vaccine strain is a live attenuated virus that is routinely administered
      to children in the United States and Europe to prevent chickenpox. It is
      effective and safe but occasionally produces a rash. The vaccine virus has
      accumulated mutations during its attenuation, but the rashes are not explained by
      their reversion, unlike complications reported for other viral vaccines. Indeed,
      most of the novel mutations distinguishing the Oka vaccine from the more virulent
      parental virus have not actually become fixed. Because the parental alleles are
      still present, the vaccine is polymorphic at >30 loci and therefore contains a
      mixture of related viruses. The inoculation of >40 million patients has
      consequently created a highly replicated evolutionary experiment that we have
      used to assess the competitive ability of these different viral genotypes in a
      human host. Using virus recovered from rash vesicles, we show that two vaccine
      mutations, causing amino acid substitutions in the major transactivating protein
      IE62, are outcompeted by the ancestral alleles. Standard interpretations of
      varicella disease severity concentrate on the undeniably important effects of
      host genotype and immune status, yet our results allow us to demonstrate that the
      viral genotype is associated with virulence and to identify the key sites. We
      propose that these loci have pleiotropic effects on the immunogenic properties of
      the virus, rash formation, and its epidemiological spread, which mould the
      evolution of its virulence. These findings are of practical importance for
      reducing the incidence of vaccine-associated rash and promoting public acceptance
      of the vaccine.

PMID- 17182748
TI  - Divergence of reproductive phenology under climate warming.
AB  - Because the flowering and fruiting phenology of plants is sensitive to
      environmental cues such as temperature and moisture, climate change is likely to
      alter community-level patterns of reproductive phenology. Here we report a
      previously unreported phenomenon: experimental warming advanced flowering and
      fruiting phenology for species that began to flower before the peak of summer
      heat but delayed reproduction in species that started flowering after the peak
      temperature in a tallgrass prairie in North America. The warming-induced
      divergence of flowering and fruiting toward the two ends of the growing season
      resulted in a gap in the staggered progression of flowering and fruiting in the
      community during the middle of the season. A double precipitation treatment did
      not significantly affect flowering and fruiting phenology. Variation among
      species in the direction and magnitude of their response to warming caused
      compression and expansion of the reproductive periods of different species,
      changed the amount of overlap between the reproductive phases, and created
      possibilities for an altered selective environment to reshape communities in a
      future warmed world.

PMID- 17182749
TI  - Positive affect increases the breadth of attentional selection.
AB  - The present study examined the thesis that positive affect may serve to broaden
      the scope of attentional filters, reducing their selectivity. The effect of
      positive mood states was measured in two different cognitive domains: semantic
      search (remote associates task) and visual selective attention (Eriksen flanker
      task). In the conceptual domain, positive affect enhanced access to remote
      associates, suggesting an increase in the scope of semantic access. In the
      visuospatial domain, positive affect impaired visual selective attention by
      increasing processing of spatially adjacent flanking distractors, suggesting an
      increase in the scope of visuospatial attention. During positive states,
      individual differences in enhanced semantic access were correlated with the
      degree of impaired visual selective attention. These findings demonstrate that
      positive states, by loosening the reins on inhibitory control, result in a
      fundamental change in the breadth of attentional allocation to both external
      visual and internal conceptual space.

PMID- 17182750
TI  - Gain-of-function mutations in complement factor B are associated with atypical
      hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) is an important cause of acute renal failure in
      children. Mutations in one or more genes encoding complement-regulatory proteins
      have been reported in approximately one-third of nondiarrheal, atypical HUS
      (aHUS) patients, suggesting a defect in the protection of cell surfaces against
      complement activation in susceptible individuals. Here, we identified a subgroup
      of aHUS patients showing persistent activation of the complement alternative
      pathway and found within this subgroup two families with mutations in the gene
      encoding factor B (BF), a zymogen that carries the catalytic site of the
      complement alternative pathway convertase (C3bBb). Functional analyses
      demonstrated that F286L and K323E aHUS-associated BF mutations are gain-of
      function mutations that result in enhanced formation of the C3bBb convertase or
      increased resistance to inactivation by complement regulators. These data expand
      our understanding of the genetic factors conferring predisposition to aHUS,
      demonstrate the critical role of the alternative complement pathway in the
      pathogenesis of aHUS, and provide support for the use of complement-inhibition
      therapies to prevent or reduce tissue damage caused by dysregulated complement
      activation.

PMID- 17182751
TI  - Vibrio cholerae strain typing and phylogeny study based on simple sequence
      repeats.
AB  - Vibrio cholerae is the etiological agent of cholera. Its natural reservoir is the
      aquatic environment. To date, practical typing of V. cholerae is mainly
      serological and requires about 200 antisera. Simple sequence repeats (SSR), also
      termed VNTR (for variable number of tandem repeats), provide a source of high
      genomic polymorphism used in bacterial typing. Here we describe an SSR-based
      typing method that combines the variation in highly mutable SSR loci, with that
      of shorter, relatively more stable mononucleotide repeat (MNR) loci, for accurate
      and rapid typing of V. cholerae. In silico screening of the V. cholerae genome
      revealed thousands of perfect SSR tracts with an average frequency of one SSR
      every 152 bp. A panel of 32 V. cholerae strains, representing both clinical and
      environmental isolates, was tested for polymorphism in SSR loci. Two strategies
      were applied to identify SSR variation: polymorphism of SSR tracts longer than 12
      bp (L-SSR) assessed by capillary fragment-size analysis and MNR polymorphism
      assessed by sequencing. The nine L-SSR loci tested were all polymorphic,
      displaying 2 to 13 alleles per locus. Sequence analysis of eight MNR-containing
      loci (MNR-multilocus sequence typing [MLST]) provided information on both
      variations in the MNR tract itself, and single nucleotide polymorphism (SNP) in
      their flanking sequences. Phylogenetic analysis of the combined SSR data showed a
      clear discrimination between the clinical strains belonging to O1 and O139
      serogroups, and the environmental isolates. Furthermore, discrimination between
      27 strains of the 32 strains was achieved. SSR-based typing methods combining L
      SSR and MNR-MLST were found to be efficient for V. cholerae typing.

PMID- 17182752
TI  - Comparative study of Kaposi's sarcoma-associated herpesvirus serological assays
      using clinically and serologically defined reference standards and latent class
      analysis.
AB  - Accurate determination of infection with Kaposi's sarcoma-associated herpesvirus
      (KSHV) has been hindered by the lack of a "gold standard" for comparison of
      serological assays used to estimate KSHV prevalence in serosurveys conducted in
      different settings. We have evaluated the performance of five in-house (developed
      at University College London [UCL], United Kingdom, and at the virology
      laboratory of the Instituto de Medicine Tropical [IMT] in Sao Paulo, Brazil) and
      two commercial (ABI and DIAVIR) serological assays to detect antibodies to
      latency-associated nuclear antigen (LANA) and to lytic KSHV antigens. We used a
      variety of serum samples assembled to represent populations likely to be at high,
      intermediate, and low risk of KSHV infection in Brazil. Composite reference
      standard panels were prepared based on clinical and serological parameters,
      against which assay performances were assessed using conventional Bayesian
      statistics and latent class analysis (LCA). Against the clinical reference
      standard, in-house immunofluorescence assays to detect anti-LANA antibodies (IFA
      LANA) produced at UCL and IMT had similar performances, with sensitivities of 61%
      (95% confidence interval [CI], 48% to 74%) and 72% (95% CI, 58% to 83%) and
      specificities of 99% (95% CI, 94% to 100%) and 100% (95% CI, 96% to 100%),
      respectively, and only the IMT IFA-LANA was included in LCA, together with the
      IMT IFA-lytic and four enzyme-linked immunosorbent assays (ELISAs). The LCA
      indicated that the IMT whole-virus ELISA performed best (sensitivity, 87% [95%
      CI, 81% to 91%]; and specificity, 100% [95% CI, 98% to 100%]), confirming the
      results obtained with the conventional statistical approach. Commercially
      available ELISA-based tests yielded the lowest specificities using a spectrum of
      serum samples. The evaluation of KSHV serological assays is warranted before
      planning serosurveys in various settings.

PMID- 17182753
TI  - A genotype-independent real-time PCR assay for quantification of hepatitis B
      virus DNA.
AB  - Accurate quantification of hepatitis B virus (HBV) DNA levels is important for
      monitoring patients with chronic HBV infection and for assessing their responses
      to antiviral therapy. This study aimed to develop a real-time PCR assay that is
      sensitive and can accurately quantify a wide range of HBV DNA levels across the
      known HBV genotypes. An "in-house" real-time PCR assay using primers and a TaqMan
      probe in a highly conserved region of the HBV surface gene was designed. The
      assay was standardized against a WHO standard and validated against plasmids of
      HBV genotypes A through H. The linear quantification range was approximately 5 x
      10(0) to 2.0 x 10(9) IU/ml. Results of samples from patients infected with HBV
      genotypes A through H tested using our real-time "in-house" PCR assay showed an
      excellent correlation with those of the Cobas Amplicor HBV Monitor (R2=0.9435)
      and the Cobas TaqMan HBV (R2=0.9873) tests. We have established a real-time PCR
      assay that is genotype independent and can accurately quantify a wide range of
      HBV DNA levels. Further studies of additional samples are ongoing to validate the
      genotype independence of our assay.

PMID- 17182754
TI  - Recurrent melioidosis: possible role of infection with multiple strains of
      Burkholderia pseudomallei.

PMID- 17182755
TI  - Comparison of Cepheid's analyte-specific reagents with BD directigen for
      detection of respiratory syncytial virus.
AB  - For detection of respiratory syncytial virus (RSV), the BD Directigen RSV rapid
      antigen assay was compared to Cepheid's real-time reverse transcriptase PCR RSV
      analyte-specific reagents. The Directigen RSV assay resulted in a 23% false
      negative rate, using PCR and chart review as the gold standard, indicating that
      rapid RSV PCR results would be advantageous.

PMID- 17182756
TI  - Evaluation of a new selective chromogenic agar medium for detection of extended
      spectrum beta-lactamase-producing Enterobacteriaceae.
AB  - A novel chromogenic agar medium (ESBL-Bx; bioMerieux, Marcy l'Etoile, France) was
      compared to MacConkey agar supplemented with 2 mg ceftazidime/liter (MCKC) for
      the selective isolation and presumptive identification of extended-spectrum beta
      lactamase (ESBL)-producing Enterobacteriaceae directly from clinical samples. Of
      a total of 644 clinical specimens (including 551 fecal samples), 496 yielded no
      growth and 148 yielded growth on one or both media. Overall, 44 ESBL-producing
      Enterobacteriaceae strains (Escherichia coli [n=17], Enterobacter aerogenes
      [n=17], Klebsiella spp. [n=5], and Citrobacter freundii [n=5]) were isolated from
      37 specimens by a combination of both methods after 18 to 24 h of incubation. The
      sensitivities were 97.7 and 84.1% for ESBL-Bx and MCKC, respectively, with 43
      ESBL-positive strains isolated as colored colonies from 36 specimens on ESBL-Bx
      versus 37 ESBL-positive organisms isolated from 32 specimens on MCKC. The
      specificities by specimens were 89 and 91% for ESBL-Bx and MCKC, respectively. On
      either one of the two media, natural AmpC-hyperproducing Enterobacter spp. (n=25)
      and Citrobacter spp. (n=14) were the most common false positives as well as non
      ESBL-producing Klebsiella oxytoca (n=18) on ESBL-Bx and Morganella morganii
      (n=10) on MCKC. We conclude that ESBL-Bx is a sensitive and specific medium for
      the isolation of ESBL-producing Enterobacteriaceae from clinical samples. The
      main advantages of ESBL-Bx over MCKC reside in its chromogenic character and its
      sensitivity and selectivity, which enabled the recovery and presumptive
      identification of most ESBL-producing Enterobacteriaceae within 24 h and reduced
      by 27% the need for unnecessary identification and confirmation of ESBL testing
      when disregarding all colorless colonies growing on this medium.

PMID- 17182757
TI  - GeneChip resequencing of the smallpox virus genome can identify novel strains: a
      biodefense application.
AB  - We developed a set of seven resequencing GeneChips, based on the complete genome
      sequences of 24 strains of smallpox virus (variola virus), for rapid
      characterization of this human-pathogenic virus. Each GeneChip was designed to
      analyze a divergent segment of approximately 30,000 bases of the smallpox virus
      genome. This study includes the hybridization results of 14 smallpox virus
      strains. Of the 14 smallpox virus strains hybridized, only 7 had sequence
      information included in the design of the smallpox virus resequencing GeneChips;
      similar information for the remaining strains was not tiled as a reference in
      these GeneChips. By use of variola virus-specific primers and long-range PCR, 22
      overlapping amplicons were amplified to cover nearly the complete genome and
      hybridized with the smallpox virus resequencing GeneChip set. These GeneChips
      were successful in generating nucleotide sequences for all 14 of the smallpox
      virus strains hybridized. Analysis of the data indicated that the GeneChip
      resequencing by hybridization was fast and reproducible and that the smallpox
      virus resequencing GeneChips could differentiate the 14 smallpox virus strains
      characterized. This study also suggests that high-density resequencing GeneChips
      have potential biodefense applications and may be used as an alternate tool for
      rapid identification of smallpox virus in the future.

PMID- 17182758
TI  - Rapid and highly sensitive pathotyping of avian influenza A H5N1 virus by using
      real-time reverse transcription-PCR.
AB  - Rapid typing of the pathogenicity of avian influenza A viruses (AIV) of subtypes
      H5 and H7 is crucial to initiate adequate protective measures preventing the
      spread of highly pathogenic AIV (HPAIV). Here, a new real-time reverse
      transcription-PCR assay which enables sensitive and specific detection and
      cleavage site analysis of HPAIV H5N1 of the Qinghai lineage is described.

PMID- 17182759
TI  - Vancomycin-resistant Enterococcus faecalis endocarditis: linezolid failure and
      strain characterization of virulence factors.
AB  - Infective endocarditis due to vancomycin-resistant (VR) Enterococcus faecalis has
      only rarely been reported. We report a case of VR E. faecalis endocarditis that
      failed to respond to linezolid therapy, outline the virulence traits of the
      isolate, and review previously published cases of VR E. faecalis endocarditis.

PMID- 17182760
TI  - Use of new T-cell-based cell lines expressing two luciferase reporters for
      accurately evaluating susceptibility to anti-human immunodeficiency virus type 1
      drugs.
AB  - Two new T-cell-based reporter cell lines were established to measure human
      immunodeficiency virus type 1 (HIV-1) infectivity. One cell line naturally
      expresses CD4 and CXCR4, making it susceptible to X4-tropic viruses, and the
      other cell line, in which a CCR5 expression vector was introduced, is susceptible
      to both X4- and R5-tropic viruses. Reporter cells were constructed by
      transfecting the human T-cell line HPB-Ma, which demonstrates high susceptibility
      to HIV-1, with genomes expressing two different luciferase reporters, HIV-1 long
      terminal repeat-driven firefly luciferase and cytomegalovirus promoter-driven
      renilla luciferase. Upon HIV infection, the cells expressed firefly luciferase at
      levels that were highly correlated (r2=0.91 to 0.98) with the production of the
      capsid antigen p24. The cells also constitutively expressed renilla luciferase,
      which was used to monitor cell numbers and viability. The reliability of the cell
      lines for two in vitro applications, drug resistance phenotyping and drug
      screening, was confirmed. As HIV-1 efficiently replicated in these cells, they
      could be used for multiple-round replication assays as an alternative method to a
      single-cycle replication protocol. Coefficients of variation for drug
      susceptibility evaluated with the cell lines ranged from 17 to 41%. The new cell
      lines were beneficial for evaluating antiretroviral drug resistance. Firefly
      luciferase gave a wider dynamic range for evaluating virus infectivity, and the
      introduction of renilla luciferase improved assay reproducibility. The cell lines
      were also beneficial for screening new antiretroviral agents, as false inhibition
      caused by the cytotoxicity of test compounds was easily detected by monitoring
      renilla luciferase activity.

PMID- 17182761
TI  - Dose-dependent immune response to Mycobacterium bovis BCG vaccination in
      neonates.
AB  - In 10-week-old infants vaccinated at birth with Japanese Mycobacterium bovis BCG,
      the number of dermal needle penetrations correlated positively with frequency of
      proliferating CD4(+) T cells in whole blood following BCG stimulation for 6 days
      but did not correlate with secreted cytokine levels after 7 h or interferon
      CD4(+) T-cell frequency after 12 h of BCG stimulation.

PMID- 17182762
TI  - Development of serological assays for Thottapalayam virus, an insectivore-borne
      Hantavirus.
AB  - Thottapalayam virus (TPMV), a member of the genus Hantavirus in the family
      Bunyaviridae, was isolated from an insectivore, Suncus murinus (musk shrew),
      captured in southern India in 1964. While the isolation of TPMV predates the
      discovery of the prototype Hantaan virus, little is known about its genetics and
      biology. To date, preliminary evidence suggests that TPMV differs significantly,
      both antigenically and genetically, from all known rodent-borne hantaviruses.
      However, since detailed epizootiological studies have not been conducted, it is
      unclear if TPMV is naturally harbored by an insectivore host or if TPMV
      represents a "spillover" from its natural rodent reservoir host. Moreover, to
      what extent TPMV causes infection and/or disease in humans is not known. To
      address these issues, we first studied the antigenic profile of TPMV using
      monoclonal antibodies against Hantaan and Seoul viruses and polyclonal immune
      sera against Puumala virus and TPMV. Armed with this newfound information, we
      developed an enzyme-linked immunosorbent assay system for the diagnosis of TPMV
      infections in shrews and humans, using a recombinant TPMV N antigen manipulated
      to have an E5/G6 epitope to be captured by monoclonal antibody clone E5/G6. Using
      this assay, we found anti-TPMV antibodies in sera from a patient with high fever
      of unknown etiology in Thailand and from two shrews captured in Indonesia.
      Seropositivity was verified by the indirect immunofluorescence antibody test,
      Western blotting analysis, and focus reduction neutralization test. Collectively,
      our data indicate that TPMV is harbored by Suncus murinus as its host in nature
      and is capable of infecting humans.

PMID- 17182763
TI  - Neuron-specific conditional expression of a mitochondrially targeted fluorescent
      protein in mice.
AB  - Mitochondrial dysfunction contributes to the pathophysiology of both acute and
      chronic neurodegenerative disorders. Quantification of mitochondrial bioenergetic
      properties generally requires the use of isolated brain mitochondria. However,
      the involvement of neuronal mitochondrial dysfunction in these disorders is
      limited by the lack of markers, and therefore isolation procedures, that
      distinguish neuronal compared with astrocyte mitochondria. To address this and
      other issues concerning neuronal mitochondria in the CNS, transgenic mice were
      generated that express a fluorescent protein targeted specifically to neurons. A
      neuron-specific promoter, CaMKIIalpha (calcium/calmodulin-dependent kinase
      IIalpha) driven tTA (tetracycline transactivator) mice were crossed with TRE
      (tetracycline responsive element) driven mitochondrial targeted enhanced yellow
      fluorescent protein (eYFP) mice. Expression of eYFP in the bigenic mouse brain
      was observed only in neuronal mitochondria of striatum, forebrain, and
      hippocampus and was enhanced by the removal of the tetracycline analog
      doxycycline (Dox) in the diet. The respiratory control ratio of synaptic and
      nonsynaptic mitochondria isolated from eYFP-expressing mice was the same as
      control mice, suggesting that neuronal mitochondria expressing eYFP maintain
      normal bioenergetic functions. More importantly, the development of Dox
      inducible, neuron targeted mito/eYFP transgenic mice offer a unique in vivo model
      for delineating the participation of neuronal mitochondria in neuronal survival
      and death.

PMID- 17182764
TI  - Two retinotopic visual areas in human lateral occipital cortex.
AB  - We describe two visual field maps, lateral occipital areas 1 (LO1) and 2 (LO2),
      in the human lateral occipital cortex between the dorsal part of visual area V3
      and visual area V5/MT+. Each map contained a topographic representation of the
      contralateral visual hemifield. The eccentricity representations were shared with
      V1/V2/V3. The polar angle representation in LO1 extended from the lower vertical
      meridian (at the boundary with dorsal V3) through the horizontal to the upper
      vertical meridian (at the boundary with LO2). The polar angle representation in
      LO2 was the mirror-reversal of that in LO1. LO1 and LO2 overlapped with the
      posterior part of the object-selective lateral occipital complex and the kinetic
      occipital region (KO). The retinotopy and functional properties of LO1 and LO2
      suggest that they correspond to two new human visual areas, which lack exact
      homologues in macaque visual cortex. The topography, stimulus selectivity, and
      anatomical location of LO1 and LO2 indicate that they integrate shape information
      from multiple visual submodalities in retinotopic coordinates.

PMID- 17182765
TI  - Apparent encoding of sequential context in rat medial prefrontal cortex is
      accounted for by behavioral variability.
AB  - Simple sequences can be represented via asymmetrically linked neural assemblies,
      provided that the elements of the sequence are unique. When elements repeat,
      however (e.g., A-B-C-B-A), the same element belongs to two separate "sequential
      contexts," and a more complex encoding mechanism is required. To enable correct
      sequence performance, some neural structure must provide a disambiguating signal
      that differentiates the two sequential contexts (i.e., B as an element of "A-B"
      as opposed to "C-B"). The disambiguating signal may derive from a form of working
      memory, or, in some cases, a simple timing mechanism may suffice. To investigate
      the possible role of medial prefrontal cortex in complex sequence encoding, rats
      were trained on a spatial sequence containing two adjacent repeated segments
      (e.g., A-B-C-D-B-C-E). The double-repeat procedure minimized behavioral
      differences in the second leg (C) of the repeat subsequence that arise in the
      first leg (B) because of differences in the entry point (e.g., A-B vs D-B). Far
      more cells were context sensitive along the first leg than along the second (36
      vs 9%), and most of the differences were accounted for by systematic variations
      in the rat's trajectory, which were much larger along the first leg. There is
      thus little evidence for sequential context-discriminative activity in the medial
      prefrontal cortex that cannot plausibly be accounted for by context-dependent
      behavior. The finding that the rodent medial prefrontal cortex is highly
      sensitive to sensory-behavioral variables raises doubts about previous
      experiments that purport to show working memory-related activity in this region.

PMID- 17182766
TI  - NR3A modulates the outer vestibule of the "NMDA" receptor channel.
AB  - Classical NMDA receptors (NMDARs), activated by glycine and glutamate, are
      heteromultimers comprised of NR1 and NR2 subunits. Coexpression of the novel NR3
      family of NMDAR subunits decreases the magnitude of NR1/NR2 receptor-mediated
      currents or forms glycine-activated channels with the NR1 subunit alone. The
      second (M2) and third (M3) membrane segments of NR1 and NR2 subunits of classical
      NMDARs form the core of the channel permeation pathway. Structural information
      regarding NR1/NR3 channels remains unknown. Using the Xenopus oocyte expression
      system and the SCAM (substituted cysteine accessibility method), we found that M3
      segments of both NR1 and NR3A form a narrow constriction in the outer vestibule
      of the channel, which prevents passage of externally applied sulfhydryl-specific
      agents. The most internal reactive residue in each M3 segment is the threonine in
      the conserved SYTANLAAF motif. These threonines appear to be symmetrically
      aligned. Several NR3A M3 mutations change the behavior of NR1/NR3A channels.
      Unlike NR1, however, the M3 segment of NR3A does not undergo extensive molecular
      rearrangement during channel gating by added glycine. Additionally, in the M2
      segment, our data suggest that the amino acid at the asparagine (N) site of NR1,
      but not NR3A, contributes to the selectivity filter of NR1/3A channels. We
      therefore conclude that NR3A modulates the NR1/NR3A permeation pathway via a
      novel mechanism of forming a narrow constriction at the outer channel vestibule.
      This modified channel vestibule may also explain the dominant-negative effect of
      the NR3 subunit on channel behavior when coexpressed with NR1 and NR2 subunits.

PMID- 17182767
TI  - Deletion of the Ttf1 gene in differentiated neurons disrupts female reproduction
      without impairing basal ganglia function.
AB  - Thyroid transcription factor 1 (TTF1) [also known as Nkx2.1 (related to the NK-2
      class of homeobox genes) and T/ebp (thyroid-specific enhancer-binding protein)],
      a homeodomain gene required for basal forebrain morphogenesis, remains expressed
      in the hypothalamus after birth, suggesting a role in neuroendocrine function.
      Here, we show an involvement of TTF1 in the control of mammalian puberty and
      adult reproductive function. Gene expression profiling of the nonhuman primate
      hypothalamus revealed that TTF1 expression increases at puberty. Mice in which
      the Ttf1 gene was ablated from differentiated neurons grew normally and had
      normal basal ganglia/hypothalamic morphology but exhibited delayed puberty,
      reduced reproductive capacity, and a short reproductive span. These defects were
      associated with reduced hypothalamic expression of genes required for sexual
      development and deregulation of a gene involved in restraining puberty. No
      extrapyramidal impairments associated with basal ganglia dysfunction were
      apparent. Thus, although TTF1 appears to fulfill only a morphogenic function in
      the ventral telencephalon, once this function is satisfied in the hypothalamus,
      TTF1 remains active as part of the transcriptional machinery controlling female
      sexual development.

PMID- 17182768
TI  - Mechanisms of efferent-mediated responses in the turtle posterior crista.
AB  - To study the cellular mechanisms of efferent actions, we recorded from vestibular
      nerve afferents close to the turtle posterior crista while efferent fibers were
      electrically stimulated. Efferent-mediated responses were obtained from calyx
      bearing (CD, calyx and dimorphic) afferents and from bouton (B) afferents
      distinguished by their neuroepithelial locations into BT units near the torus and
      BM units at intermediate sites. The spike discharge of CD units is strongly
      excited by efferent stimulation, whereas BT and BM units are inhibited, with BM
      units also showing a postinhibitory excitation. Synaptic activity was recorded
      intracellularly after spikes were blocked. Responses of BT/BM units to single
      efferent shocks consist of a brief depolarization followed by a prolonged
      hyperpolarization. Both components reflect variations in hair-cell quantal
      release rates and are eliminated by pharmacological antagonists of alpha9/alpha10
      nicotinic receptors. Blocking calcium-dependent SK potassium channels converts
      the biphasic response into a prolonged depolarization. Results can be explained,
      as in other hair-cell systems, by the sequential activation of alpha9/alpha10 and
      SK channels. In BM units, the postinhibitory excitation is based on an increased
      rate of hair-cell quanta and depends on the preceding inhibition. There is, in
      addition, an efferent-mediated, direct depolarization of BT/BM and CD fibers. In
      CD units, it is the exclusive efferent response. Nicotinic antagonists have
      different effects on hair-cell efferent actions and on the direct depolarization
      of CD and BT/BM units. Ultrastructural studies, besides confirming the efferent
      innervation of type II hair cells and calyx endings, show that turtle efferents
      commonly contact afferent boutons terminating on type II hair cells.

PMID- 17182769
TI  - Modulation of neural activity during observational learning of actions and their
      sequential orders.
AB  - How does the brain transform perceptual representations of others' actions into
      motor representations that can be used to guide behavior? Here we used functional
      magnetic resonance imaging to record human brain activity while subjects watched
      others construct multipart objects under varied task demands. We find that
      relative to resting baseline, passive action observation increases activity
      within inferior frontal and parietal cortices implicated in action encoding
      (mirror system) and throughout a distributed network of areas involved in motor
      representation, including dorsal premotor cortex, pre-supplementary motor area,
      cerebellum, and basal ganglia (experiments 1 and 2). Relative to passive
      observation, these same areas show increased activity when subjects observe with
      the intention to subsequently reproduce component actions using the demonstrated
      sequential procedures (experiment 1). Observing the same actions with the
      intention of reproducing component actions, but without the requirement to use
      the demonstrated sequential procedure, increases activity in the same regions,
      although to a lesser degree (experiment 2). These findings demonstrate that when
      attempting to learn behaviors through observation, the observers' intentions
      modulate responses in a widely distributed network of cortical and subcortical
      regions implicated previously in action encoding and/or motor representation.
      Among these regions, only activity within the right intraparietal sulcus predicts
      the accuracy with which observed procedures are subsequently performed.
      Successful formation of motor representations of sequential procedures through
      observational learning is dependent on computations implemented within this
      parietal region.

PMID- 17182770
TI  - Connecdenn, a novel DENN domain-containing protein of neuronal clathrin-coated
      vesicles functioning in synaptic vesicle endocytosis.
AB  - Clathrin-coated vesicles (CCVs) are responsible for the endocytosis of multiple
      cargo, including synaptic vesicle membranes. We now describe a new CCV protein,
      termed connecdenn, that contains an N-terminal DENN (differentially expressed in
      neoplastic versus normal cells) domain, a poorly characterized protein module
      found in multiple proteins of unrelated function and a C-terminal peptide motif
      domain harboring three distinct motifs for binding the alpha-ear of the clathrin
      adaptor protein 2 (AP-2). Connecdenn coimmunoprecipitates and partially
      colocalizes with AP-2, and nuclear magnetic resonance and peptide competition
      studies reveal that all three alpha-ear-binding motifs contribute to AP-2
      interactions. In addition, connecdenn contains multiple Src homology 3 (SH3)
      domain-binding motifs and coimmunoprecipitates with the synaptic SH3 domain
      proteins intersectin and endophilin A1. Interestingly, connecdenn is enriched on
      neuronal CCVs and is present in the presynaptic compartment of neurons. Moreover,
      connecdenn has a uniquely stable association with CCV membranes because it
      resists extraction with Tris and high-salt buffers, unlike most other CCV
      proteins, but it is not detected on purified synaptic vesicles. Together, these
      observations suggest that connecdenn functions on the endocytic limb of the
      synaptic vesicle cycle. Accordingly, disruption of connecdenn interactions with
      its binding partners through overexpression of the C-terminal peptide motif
      domain or knock down of connecdenn through lentiviral delivery of small hairpin
      RNA both lead to defects in synaptic vesicle endocytosis in cultured hippocampal
      neurons. Thus, we identified connecdenn as a component of the endocytic machinery
      functioning in synaptic vesicle endocytosis, providing the first evidence of a
      role for a DENN domain-containing protein in endocytosis.

PMID- 17182771
TI  - Preference for immediate over delayed rewards is associated with magnitude of
      ventral striatal activity.
AB  - Discounting future outcomes as a function of their deferred availability
      underlies much of human decision making. Discounting, or preference for immediate
      over delayed rewards of larger value, is often associated with impulsivity and is
      a risk factor for addictive disorders such as pathological gambling, cigarette
      smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in
      mediating behavioral responses and physiological states associated with reward,
      and dysregulation of the VS contributes to addiction, perhaps by affecting
      impulsive decision-making. Behavioral tests of delay discounting (DD), which
      index preference for smaller immediate over larger delayed rewards, covary with
      impulsive tendencies in humans. In the current study, we examined the
      relationship between individual differences in DD, measured in a behavioral
      assessment, and VS activity measured with blood oxygenation level-dependent
      functional magnetic resonance imaging, in 45 adult volunteers. VS activity was
      determined using a task involving positive and negative feedback with monetary
      reward. Analyses revealed that individual differences in DD correlate positively
      with magnitude of VS activation in response to both positive and negative
      feedback, compared with a no-feedback control condition. Variability in DD was
      also associated with differential VS activation in response to positive, compared
      with negative, feedback. Collectively, our results suggest that increased
      preference for smaller immediate over larger delayed rewards reflects both a
      relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a
      specific neurocognitive mechanism that may contribute to increased risk for
      addiction.

PMID- 17182772
TI  - Brain-derived neurotrophic factor participates in determination of neuronal
      laminar fate in the developing mouse cerebral cortex.
AB  - Lamina formation in the developing cerebral cortex requires precisely regulated
      generation and migration of the cortical progenitor cells. To test the possible
      involvement of brain-derived neurotrophic factor (BDNF) in the formation of the
      cortical lamina, we investigated the effects of BDNF protein and anti-BDNF
      antibody separately administered into the telencephalic ventricular space of 13.5
      d-old mouse embryos. BDNF altered the position, gene-expression properties, and
      projections of neurons otherwise destined for layer IV to those of neurons for
      the deeper layers, V and VI, of the cerebral cortex, whereas anti-BDNF antibody
      changed some of those of neurons of upper layers II/III. Additional analysis
      revealed that BDNF altered the laminar fate of neurons only if their parent
      progenitor cells were exposed to it at approximately S-phase and that it hastened
      the timing of the withdrawal of their daughter neurons from the ventricular
      proliferating pool by accelerating the completion of S-phase, downregulation of
      the Pax6 (paired box gene 6) expression, an essential transcription factor for
      generation of the upper layer neurons, and interkinetic nuclear migration of
      cortical progenitors in the ventricular zone. These observations suggest that
      BDNF participates in the processes forming the neuronal laminas in the developing
      cerebral cortex. BDNF can therefore be counted as one of the key extrinsic
      factors that regulate the laminar fate of cortical neurons.

PMID- 17182773
TI  - Neural correlates of vibrotactile working memory in the human brain.
AB  - Recent neurophysiological studies in macaques identified a network of brain
      regions related to vibrotactile working memory (WM), including somatosensory,
      motor, premotor, and prefrontal cortex. In these studies, monkeys decided which
      of two vibrotactile stimuli that were sequentially applied to their fingertips
      and separated by a short delay had the higher vibration frequency. Using the same
      task, the objective of the present study was to identify the neural correlates
      related to the different task periods (encoding, maintenance, and decision
      making) of vibrotactile WM in the human brain. For this purpose, we used event
      related functional magnetic resonance imaging and contrasted WM trials with a
      control condition of vibrotactile stimulation that did not require maintenance
      and decision making. We found that vibrotactile WM has a similar but not
      identical neural organization in humans and monkeys. Consistent with
      neurophysiological data in monkeys and behavioral studies in humans, the primary
      somatosensory and the ventral premotor cortex exhibited increased activity during
      encoding. Maintenance of a vibrotactile memory trace evoked activity in the
      premotor and ventrolateral prefrontal cortex. Decision making caused activation
      in the somatosensory, premotor, and lateral prefrontal cortex. However, human
      vibrotactile WM recruited additional areas. Decision making activated a broader
      network than that studied thus far in monkeys. Maintenance and decision making
      additionally activated the inferior parietal lobe. Although the different task
      components evoked activity in distinctive neural networks, there was considerable
      overlap of activity, especially regarding maintenance and decision making,
      indicating that similar neural mechanisms are required for the subprocesses
      related to these task components.

PMID- 17182774
TI  - Ca2+ from one or two channels controls fusion of a single vesicle at the frog
      neuromuscular junction.
AB  - Neurotransmitter release is triggered by the cooperative action of approximately
      five Ca2+ ions entering the presynaptic terminal through Ca2+ channels. Depending
      on the organization of the active zone (AZ), influx through one or many channels
      may be needed to cause fusion of a vesicle. Using a combination of experiments
      and modeling, we examined the number of channels that contribute Ca2+ for fusion
      of a single vesicle in a frog neuromuscular AZ. We compared Ca2+ influx to
      neurotransmitter release by measuring presynaptic action potential-evoked (AP
      evoked) Ca2+ transients simultaneously with postsynaptic potentials. Ca2+ influx
      was manipulated by changing extracellular [Ca2+] (Ca(ext)) to alter the flux per
      channel or by reducing the number of open Ca2+ channels with omega-conotoxin GVIA
      (omega-CTX). When Ca(ext) was reduced, the exponent of the power relationship
      relating release to Ca2+ influx was 4.16 +/- 0.62 (SD; n = 4), consistent with a
      biochemical cooperativity of approximately 5. In contrast, reducing influx with
      omega-CTX yielded a power relationship of 1.7 +/- 0.44 (n = 5) for Ca(ext) of 1.8
      mM and 2.12 +/- 0.44 for Ca(ext) of 0.45 mM (n = 5). Using geometrically
      realistic Monte Carlo simulations, we tracked Ca2+ ions as they entered through
      each channel and diffused in the terminal. Experimental and modeling data were
      consistent with two to six channel openings per AZ per AP; the Ca2+ that causes
      fusion of a single vesicle originates from one or two channels. Channel
      cooperativity depends mainly on the physical relationship between channels and
      vesicles and is insensitive to changes in the non-geometrical parameters of our
      model.

PMID- 17182775
TI  - Local edge detectors: a substrate for fine spatial vision at low temporal
      frequencies in rabbit retina.
AB  - Visual acuity is limited by the size and density of the smallest retinal ganglion
      cells, which correspond to the midget ganglion cells in primate retina and the
      beta-ganglion cells in cat retina, both of which have concentric receptive fields
      that respond at either light-On or light-Off. In contrast, the smallest ganglion
      cells in the rabbit retina are the local edge detectors (LEDs), which respond to
      spot illumination at both light-On and light-Off. However, the LEDs do not
      predominate in the rabbit retina and the question arises, what role do they play
      in fine spatial vision? We studied the morphology and physiology of LEDs in the
      isolated rabbit retina and examined how their response properties are shaped by
      the excitatory and inhibitory inputs. Although the LEDs comprise only
      approximately 15% of the ganglion cells, neighboring LEDs are separated by 30-40
      microm on the visual streak, which is sufficient to account for the grating
      acuity of the rabbit. The spatial and temporal receptive-field properties of LEDs
      are generated by distinct inhibitory mechanisms. The strong inhibitory surround
      acts presynaptically to suppress both the excitation and the inhibition elicited
      by center stimulation. The temporal properties, characterized by sluggish onset,
      sustained firing, and low bandwidth, are mediated by the temporal properties of
      the bipolar cells and by postsynaptic interactions between the excitatory and
      inhibitory inputs. We propose that the LEDs signal fine spatial detail during
      visual fixation, when high temporal frequencies are minimal.

PMID- 17182776
TI  - Previous experience with behavioral control over stress blocks the behavioral and
      dorsal raphe nucleus activating effects of later uncontrollable stress: role of
      the ventral medial prefrontal cortex.
AB  - Previous experience with stressors over which the subject has behavioral control
      blocks the typical behavioral consequences of subsequent exposure to stressors
      over which the organism has no behavioral control. The present experiments
      explored the involvement of the ventral medial prefrontal cortex (mPFCv) in
      mediating this "immunizing" or resilience producing effect of an initial
      experience with control. Behavioral immunization was blocked by inactivation of
      the mPFCv with muscimol at the time of the initial experience with control, as
      well as at the time of the later exposure to uncontrollable stress. Inhibition of
      protein synthesis within the mPFCv by anisomycin also blocked immunization when
      administered at the time of the initial controllable stress but had no effect
      when administered at the time of the later uncontrollable stress. Additional
      experiments found that the initial experience with control blocks the intense
      activation of serotonergic cells in the dorsal raphe nucleus that would normally
      be produced by uncontrollable stress, providing a mechanism for behavioral
      immunization. Furthermore, mPFCv activity during the initial controllable
      stressor was required for this effect to occur. These results suggest that the
      mPFCv is needed both to process information about the controllability of
      stressors and to utilize such information to regulate responses to subsequent
      stressors. Moreover, the mPFCv may be a site of storage or plasticity concerning
      controllability information. These results are consistent with recent research in
      other domains that explore the functions of the mPFCv.

PMID- 17182777
TI  - Molecular interaction between projection neuron precursors and invading
      interneurons via stromal-derived factor 1 (CXCL12)/CXCR4 signaling in the
      cortical subventricular zone/intermediate zone.
AB  - Most cortical interneurons are generated in the subpallial ganglionic eminences
      and migrate tangentially to their final destinations in the neocortex. Within the
      cortex, interneurons follow mainly stereotype routes in the subventricular
      zone/intermediate zone (SVZ/IZ) and in the marginal zone. It has been suggested
      that interactions between invading interneurons and locally generated projection
      neurons are implicated in the temporal and spatial regulation of the invasion
      process. However, so far experimental evidence for such interactions is lacking.
      We show here that the chemokine stromal-derived factor 1 (SDF-1; CXCL12) is
      expressed in the main invasion route for cortical interneurons in the SVZ/IZ.
      Most SDF-1-positive cells are proliferating and express the homeodomain
      transcription factors Cux1 and Cux2. Using MASH-1 mutant mice in concert with the
      interneuron marker DLX, we exclude that interneurons themselves produce the
      chemokine in an autocrine manner. We conclude that the SDF-1-expressing cell
      population represents the precursors of projection neurons during their
      transition and amplification in the SVZ/IZ. Using mice lacking the SDF-1 receptor
      CXCR4 or Pax6, we demonstrate that SDF-1 expression in the cortical SVZ/IZ is
      essential for recognition of this pathway by interneurons. These results
      represent the first evidence for a molecular interaction between precursors of
      projection neurons and invading interneurons during corticogenesis.

PMID- 17182778
TI  - Subcutaneous Nogo receptor removes brain amyloid-beta and improves spatial memory
      in Alzheimer's transgenic mice.
AB  - The production and aggregation of cerebral amyloid-beta (Abeta) peptide are
      thought to play a causal role in Alzheimer's disease (AD). Previously, we found
      that the Nogo-66 receptor (NgR) interacts physically with both Abeta and the
      amyloid precursor protein (APP). The inverse correlation of Abeta levels with NgR
      levels within the brain may reflect regulation of Abeta production and/or Abeta
      clearance. Here, we assess the potential therapeutic benefit of peripheral NgR
      mediated Abeta clearance in APPswe/PSEN-1deltaE9 transgenic mice. Through site
      directed mutagenesis, we demonstrate that the central 15-28 aa of Abeta associate
      with specific surface-accessible patches on the leucine-rich repeat concave side
      of the solenoid structure of NgR. In transgenic mice, subcutaneous NgR(310)ecto
      Fc treatment reduces brain Abeta plaque load while increasing the relative levels
      of serum Abeta. These changes in Abeta are correlated with improved spatial
      memory in the radial arm water maze. The benefits of peripheral NgR
      administration are evident when therapy is initiated after disease onset. Thus,
      the peripheral association of NgR(310)ecto-Fc with central Abeta residues
      provides an effective therapeutic approach for AD.

PMID- 17182779
TI  - c-Fos facilitates the acquisition and extinction of cocaine-induced persistent
      changes.
AB  - Development of drug addiction involves persistent neurobiological changes. The
      dopamine D1 receptor is involved in mediating cocaine-induced neuroadaptation,
      yet the underlying intracellular mechanisms remain unclear. We examined a
      potential role of the immediate early gene Fos, which is robustly and rapidly
      induced by cocaine via D1 receptors, in mediating cocaine-induced persistent
      neurobiological changes by creating and analyzing a mouse in which Fos is
      primarily disrupted in D1 receptor-expressing neurons in the brain. We show that
      the expression levels of several transcription factors, neurotransmitter
      receptors, and intracellular signaling molecules induced by repeated cocaine
      administration are altered in Fos-deficient brains. Dendritic remodeling of
      medium spiny neurons induced by repeated exposure to cocaine is blunted in the
      mutant mice. The mutant mice exhibit attenuated behavioral sensitization after
      repeated exposure to cocaine and more persistent memory of cocaine-induced
      conditioned place preference. Our findings indicate that c-Fos produced in D1
      receptor-expressing neurons integrates mechanisms to facilitate both the
      acquisition and extinction of cocaine-induced persistent changes.

PMID- 17182780
TI  - Primary afferent synapses on developing and adult Renshaw cells.
AB  - The mechanisms that diversify adult interneurons from a few pools of embryonic
      neurons are unknown. Renshaw cells, Ia inhibitory interneurons (IaINs), and
      possibly other types of mammalian spinal interneurons have common embryonic
      origins within the V1 group. However, in contrast to IaINs and other V1-derived
      interneurons, adult Renshaw cells receive motor axon synapses and lack
      proprioceptive inputs. Here, we investigated how this specific pattern of
      connectivity emerges during the development of Renshaw cells. Tract tracing and
      immunocytochemical markers [parvalbumin and vesicular glutamate transporter 1
      (VGLUT1)] showed that most embryonic (embryonic day 18) Renshaw cells lack dorsal
      root inputs, but more than half received dorsal root synapses by postnatal day 0
      (P0) and this input spread to all Renshaw cells by P10-P15. Electrophysiological
      recordings in neonates indicated that this input is functional and evokes Renshaw
      cell firing. VGLUT1-IR bouton density on Renshaw cells increased until P15 but
      thereafter decreased because of limited synapse proliferation coupled with the
      enlargement of Renshaw cell dendrites. In parallel, Renshaw cell postsynaptic
      densities apposed to VGLUT1-IR synapses became smaller in adult compared with
      P15. In contrast, vesicular acetylcholine transporter-IR motor axon synapses
      contact embryonic Renshaw cells and proliferate postnatally matching Renshaw cell
      growth. Like other V1 neurons, Renshaw cells are thus competent to receive
      sensory synapses. However, after P15, these sensory inputs appear deselected
      through arrested proliferation and synapse weakening. Thus, Renshaw cells shift
      from integrating sensory and motor inputs in neonates to predominantly motor
      inputs in adult. Similar synaptic weight shifts on interneurons may be involved
      in the maturation of motor reflexes and locomotor circuitry.

PMID- 17182781
TI  - The fate of old memories after medial temporal lobe damage.
AB  - Damage to the hippocampal region and related medial temporal lobe structures
      (perirhinal, entorhinal, and parahippocampal cortices) impairs new learning
      (anterograde amnesia) as well as memory for information that was acquired before
      the damage occurred (retrograde amnesia). We assessed retrograde amnesia with the
      Autobiographical Memory Interview (AMI) and with a news events test in six
      patients with damage limited primarily to the hippocampal region (H group) and
      two patients with large medial temporal lobe lesions (MTL group). On the news
      event test, the H group exhibited temporally limited retrograde amnesia covering
      approximately 5 years. On the same test, the MTL group exhibited an extensive
      retrograde amnesia covering decades. Nevertheless, performance was relatively
      spared for very remote time periods. On the AMI, all patients had intact remote
      autobiographical memory. Because our patients with hippocampal lesions, as well
      as our patients with large MTL lesions, performed normally on the AMI, patients
      who perform poorly on the same test presumably have damage beyond the hippocampus
      and related structures in the medial temporal lobe. The findings emphasize the
      difference in the extent of retrograde amnesia associated with hippocampal
      lesions and large MTL lesions.

PMID- 17182782
TI  - Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of
      neuropathic pain.
AB  - Cannabinoid-based medicines have therapeutic potential for the treatment of pain.
      Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide
      hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states.
      The aim of this study was to determine whether local inhibition of FAAH alters
      nociceptive responses of spinal neurons in the spinal nerve ligation model of
      neuropathic pain. Electrophysiological studies were performed 14-18 d after
      spinal nerve ligation or sham surgery, and the effects of the FAAH inhibitor
      cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597) on mechanically
      evoked responses of spinal neurons and levels of endocannabinoids were
      determined. Intraplantar URB597 (25 microg in 50 microl) significantly (p < 0.01)
      attenuated mechanically evoked responses of spinal neurons in sham-operated rats.
      Effects of URB597 were blocked by the cannabinoid 1 receptor (CB1) antagonist
      AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H
      pyrazole-3-carboxamide] (30 microg in 50 microl) and the opioid receptor
      antagonist naloxone. URB597 treatment increased levels of anandamide, 2
      arachidonyl glycerol, and oleoyl ethanolamide in the ipsilateral hindpaw of sham
      operated rats. Intraplantar URB597 (25 microg in 50 microl) did not, however,
      alter mechanically evoked responses of spinal neurons in spinal nerve ligated
      (SNL) rats or hindpaw levels of endocannabinoids. Intraplantar injection of a
      higher dose of URB597 (100 microg in 50 microl) significantly (p < 0.05)
      attenuated evoked responses of spinal neurons in SNL rats but did not alter
      hindpaw levels of endocannabinoids. Spinal administration of URB597 attenuated
      evoked responses of spinal neurons and elevated levels of endocannabinoids in
      sham-operated and SNL rats. These data suggest that peripheral FAAH activity may
      be altered or that alternative pathways of metabolism have greater importance in
      SNL rats.

PMID- 17182783
TI  - Netrin/DCC signaling controls contralateral dendrites of octavolateralis efferent
      neurons.
AB  - The guidance molecule Netrin and its receptor DCC (deleted in colorectal cancer)
      attract commissural axons toward the midline en route to their final destination.
      To test whether these molecules can also guide dendrites, we studied the
      contralateral dendrites of zebrafish octavolateralis efferent (OLe) neurons,
      which are unusual in that they navigate toward and cross the midline. We found
      that, at the time of dendrite outgrowth, OLe neurons express dcc, and the
      hindbrain midline expresses netrin1. Knocking down dcc or netrin1 function by
      injecting antisense morpholino oligonucleotides prevented OLe contralateral
      dendrites from crossing the midline, showing that dcc and netrin1 are necessary
      for dendrite guidance or formation. Furthermore, by transplanting cells from dcc
      morphants into wild-type embryos and vice versa, we demonstrated that dcc acts
      cell autonomously in OLe dendrites. This work is the first evidence that
      Netrin/DCC signaling acts in dendrites in a vertebrate system.

PMID- 17182784
TI  - Brain connectivity related to working memory performance.
AB  - Several brain areas show signal decreases during many different cognitive tasks
      in functional imaging studies, including the posterior cingulate cortex (PCC) and
      a medial frontal region incorporating portions of the medial frontal gyrus and
      ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these
      areas are components in a default mode network that is engaged during rest and
      disengaged during cognitive tasks. This study investigated the functional
      connectivity between the PCC and MFG/vACC during a working memory task and at
      rest by examining temporal correlations in magnetic resonance signal levels
      between the regions. The two regions were functionally connected in both
      conditions. In addition, performance on the working memory task was positively
      correlated with the strength of this functional connection not only during the
      working memory task, but also at rest. Thus, it appears these regions are
      components of a network that may facilitate or monitor cognitive performance,
      rather than becoming disengaged during cognitive tasks. In addition, these data
      raise the possibility that the individual differences in coupling strength
      between these two regions at rest predict differences in cognitive abilities
      important for this working memory task.

PMID- 17182785
TI  - An essential role for the integrin-linked kinase-glycogen synthase kinase-3 beta
      pathway during dendrite initiation and growth.
AB  - Multiple cues, including growth factors and circuit activity, signal to regulate
      the initiation and growth of mammalian dendrites. In this study, we have asked
      how these environmental cues regulate dendrite formation, and in particular,
      whether dendrite initiation and growth requires integrin-linked kinase (ILK) or
      its downstream effector, glycogen synthase kinase-3beta (GSK-3beta). In cultured
      sympathetic neurons, NGF and neuronal depolarization activated ILK and promoted
      dendrite initiation and growth, and inhibition of ILK (either pharmacologically,
      with a dominant-negative form of ILK, or by genetic knockdown) reduced
      depolarization-induced dendrite formation. In sympathetic neurons, ILK
      phosphorylated and inhibited GSK-3beta, and inhibition of GSK-3beta (either
      pharmacologically, with dominant-negative GSK-3beta, or by genetic knockdown)
      caused robust dendrite initiation. GSK-3beta inhibition also caused dendrite
      initiation in cultured cortical neurons and growth of hippocampal neurons in
      slice cultures. GSK-3beta functioned downstream of ILK to regulate dendrite
      formation, because inhibition of GSK-3beta promoted dendrite initiation even when
      ILK was simultaneously inhibited. Moreover, GSK-3beta promoted dendrite formation
      in sympathetic neurons by regulating the activity of a key dendrite formation
      effector, the MAP (microtubule-associated protein) kinase kinase (MEK)
      extracellular signal-regulated protein kinase (ERK) pathway. Specifically,
      inhibition of GSK-3beta led to increased ERK phosphorylation, and inhibition of
      MEK completely blocked the effects of GSK-3beta inhibition on dendrite initiation
      and growth. Thus, the ILK-GSK-3beta pathway plays a key role in regulating
      dendrite formation in developing mammalian neurons.

PMID- 17182786
TI  - Collapsin response mediator protein 1 mediates reelin signaling in cortical
      neuronal migration.
AB  - Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members
      that mediates signal transduction of axon guidance molecules. Here, we show
      evidence that CRMP1 is involved in Reelin (Reln) signaling to regulate neuronal
      migration in the cerebral cortex. In crmp1-/- mice, radial migration of cortical
      neurons was retarded. This phenotype was not observed in the sema3A-/- and
      crmp1+/-;sema3A+/- cortices. However, CRMP1 was colocalized with disabled-1
      (Dab1), an adaptor protein in Reln signaling. In the Reln(rl/rl) cortex, CRMP1
      and Dab1 were expressed at a higher level, yet tyrosine phosphorylated at a lower
      level. Loss of crmp1 in a dab1 heterozygous background led to the disruption of
      hippocampal lamination, a Reeler-like phenotype. In addition to axon guidance,
      CRMP1 regulates neuronal migration by mediating Reln signaling.

PMID- 17182787
TI  - Cross-whisker adaptation of neurons in the rat barrel cortex.
AB  - Neurons in the barrel cortex and the thalamus respond preferentially to
      stimulation of one whisker (the principal whisker) and weakly to several adjacent
      whiskers. Cortical neurons, unlike thalamic cells, gradually adapt to repeated
      whisker stimulations. Whether cortical adaptation is specific to the stimulated
      whisker is not known. The aim of this intracellular study was to determine
      whether the response of a cortical cell to stimulation of an adjacent whisker
      would be affected by previous adaptation induced by stimulation of the principal
      whisker and vice versa. Using a high-frequency stimulation that causes
      substantial adaptation in the cortex and much less adaptation in the thalamus, we
      show that cortical adaptation evoked by a train of stimuli applied to one whisker
      does not affect the synaptic response to subsequent stimulation of a neighboring
      whisker. Our data indicate that intrinsic mechanisms are not involved in cortical
      adaptation. Thalamic recordings obtained under the same conditions demonstrated
      that an adjacent whisker response was not generated in the thalamus, indicating
      that the observed whisker-specific adaptation results from diverging thalamic
      inputs or from cortical integration.

PMID- 17182788
TI  - G-proteins modulate cumulative inactivation of N-type (Cav2.2) calcium channels.
AB  - Precise regulation of N-type (Ca(V)2.2) voltage-gated calcium channels (Ca
      channels) controls many cellular functions including neurotransmitter and hormone
      release. One important mechanism that inhibits Ca2+ entry involves binding of G
      protein betagamma subunits (Gbetagamma) to the Ca-channels. This shifts the Ca
      channels from "willing" to "reluctant" gating states and slows activation.
      Voltage-dependent reversal of the inhibition (facilitation) is thought to reflect
      transient dissociation of Gbetagamma from the Ca-channels and can occur during
      high-frequency bursts of action potential-like waveforms (APW). Inactivation of
      Ca-channels will also limit Ca2+ entry, but it remains unclear whether G-proteins
      can modulate inactivation. In part this is because of the complex nature of
      inactivation, and because facilitation of Ca-channel currents (I(Ca)) masks the
      extent and kinetics of inactivation during typical stimulation protocols. We used
      low-frequency trains of APW to activate I(Ca). This more closely mimics
      physiological stimuli and circumvents the problem of facilitation which does not
      occur at < or = 5 Hz. Activation of endogenous G-proteins reduced both Ca2+
      dependent, and voltage-dependent inactivation of recombinant I(Ca) in human
      embryonic kidney 293 cells. This was mimicked by expression of wild-type
      Gbetagamma, but not by a point mutant of Gbetagamma with reduced affinity for Ca
      channels. A similar decrease in the inactivation of I(Ca) was produced by P2Y
      receptors in adrenal chromaffin cells. Overall, our data identify and
      characterize a novel effect of G-proteins on I(Ca), and could have important
      implications for understanding how G-protein-coupled receptors control Ca2+ entry
      and Ca2+-dependent events such as neurotransmitter and hormone release.

PMID- 17182789
TI  - Androgens regulate the development of neuropathology in a triple transgenic mouse
      model of Alzheimer's disease.
AB  - Normal age-related testosterone depletion in men is a recently identified risk
      factor for Alzheimer's disease (AD), but how androgen loss affects the
      development of AD is unclear. To investigate the relationship between androgen
      depletion and AD, we compared how androgen status affects the progression of
      neuropathology in the triple transgenic mouse model of AD (3xTg-AD). Adult male
      3xTg-AD mice were sham gonadectomized (GDX) or GDX to deplete endogenous
      androgens and then exposed for 4 months to either the androgen
      dihydrotestosterone (DHT) or to placebo. In comparison to gonadally intact 3xTg
      AD mice, GDX mice exhibited robust increases in the accumulation of beta-amyloid
      (Abeta), the protein implicated as the primary causal factor in AD pathogenesis,
      in both hippocampus and amygdala. In parallel to elevated levels of Abeta, GDX
      mice exhibited significantly impaired spontaneous alternation behavior,
      indicating deficits in hippocampal function. Importantly, DHT treatment of GDX
      3xTg-AD mice attenuated both Abeta accumulation and behavioral deficits. These
      data demonstrate that androgen depletion accelerates the development of AD-like
      neuropathology, suggesting that a similar mechanism may underlie the increased
      risk for AD in men with low testosterone. In addition, our finding that DHT
      protects against acceleration of AD-like neuropathology predicts that androgen
      based hormone therapy may be a useful strategy for the prevention and treatment
      of AD in aging men.

PMID- 17182790
TI  - Identification of process-localized mRNAs from cultured rodent hippocampal
      neurons.
AB  - The regulated translation of localized mRNAs in neurons provides a mechanism for
      spatially restricting gene expression in a synapse-specific manner. To identify
      the population of mRNAs present in distal neuronal processes of rodent
      hippocampal neurons, we grew neurons on polycarbonate filters etched with 3
      microm pores. Although the neuronal cell bodies remained on the top surface of
      the filters, dendrites, axons, and glial processes penetrated through the pores
      to grow along the bottom surface of the membrane where they could be mechanically
      separated from cell bodies. Quantitative PCR and immunochemical analyses of the
      process preparation revealed that it was remarkably free of somatic
      contamination. Microarray analysis of RNA isolated from the processes identified
      over 100 potentially localized mRNAs. In situ hybridization studies of 19 of
      these transcripts confirmed that all 19 were present in dendrites, validating the
      utility of this approach for identifying dendritically localized transcripts.
      Many of the identified mRNAs encoded components of the translational machinery
      and several were associated with the RNA-binding protein Staufen. These findings
      indicate that there is a rich repertoire of mRNAs whose translation can be
      locally regulated and support the emerging idea that local protein synthesis
      serves to boost the translational capacity of synapses.

PMID- 17182791
TI  - Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish.
AB  - As many as 10% of humans suffer chronic sleep disturbances, yet the genetic
      mechanisms that regulate sleep remain essentially unknown. It is therefore
      crucial to develop simple and cost-effective vertebrate models to study the
      genetic regulation of sleep. The best characterized mammalian sleep/wake
      regulator is hypocretin/orexin (Hcrt), whose loss results in the sleep disorder
      narcolepsy and that has also been implicated in feeding behavior, energy
      homeostasis, thermoregulation, reward seeking, addiction, and maternal behavior.
      Here we report that the expression pattern and axonal projections of embryonic
      and larval zebrafish Hcrt neurons are strikingly similar to those in mammals. We
      show that zebrafish larvae exhibit robust locomotive sleep/wake behaviors as
      early as the fifth day of development and that Hcrt overexpression promotes and
      consolidates wakefulness and inhibits rest. Similar to humans with insomnia, Hcrt
      overexpressing larvae are hyperaroused and have dramatically reduced abilities to
      initiate and maintain rest at night. Remarkably, Hcrt function is modulated by
      but does not require normal circadian oscillations in locomotor activity. Our
      zebrafish model of Hcrt overexpression indicates that the ancestral function of
      Hcrt is to promote locomotion and inhibit rest and will facilitate the discovery
      of neural circuits, genes, and drugs that regulate Hcrt function and sleep.

PMID- 17182792
TI  - Dietary soy protein isolate modifies hepatic retinoic acid receptor-beta proteins
      and inhibits their DNA binding activity in rats.
AB  - Retinoic acid receptors (RAR) belong to the same nuclear receptor superfamily as
      thyroid hormone receptors (TR) that were previously shown to be modulated by
      dietary soy protein isolate (SPI). This study has examined the effect of dietary
      SPI and isoflavones (ISF) on hepatic RAR gene expression and DNA binding
      activity. In Expt. 1, Sprague-Dawley rats were fed diets containing 20% casein or
      20% alcohol-washed SPI in the absence or presence of increasing amounts of ISF (5
      1250 mg/kg diet) for 70, 190, or 310 d. In Expt. 2, weanling Sprague-Dawley rats
      were fed diets containing 20% casein with or without supplemental ISF (50 mg/kg
      diet) or increasing amounts of alcohol-washed SPI (5, 10, and 20%) for 90 d.
      Intake of soy proteins significantly elevated hepatic RARbeta2 protein content
      dose-dependently compared with a casein diet, whereas supplemental ISF had no
      consistent effect. Neither RARbeta protein in the other tissues measured nor the
      other RAR (RARalpha and RARgamma) in the liver were affected by dietary SPI,
      indicating a tissue and isoform-specific effect of SPI. RARbeta2 mRNA abundances
      were not different between dietary groups except that its expression was markedly
      suppressed in male rats fed SPI for 310 d. DNA binding activity of nuclear
      RARbeta was significantly attenuated and the isoelectric points of RARbeta2 were
      shifted by dietary SPI. Overall, these results show for the first time, to our
      knowledge, that dietary soy proteins affect hepatic RARbeta2 protein content and
      RARbeta DNA binding activity, which may contribute to the suppression of retinoid
      induced hypertriglyceridemia by SPI as reported.

PMID- 17182793
TI  - Plasma triacylglycerol and coagulation factor concentrations predict the
      anticoagulant effect of dietary fish oil in overweight subjects.
AB  - Fish oil, containing (n-3) PUFA, is associated with a moderate reduction in
      cardiovascular disease through a multifactorial mechanism involving a decrease in
      plasma lipids and anticoagulant activity. Two intervention studies on subjects at
      risk were performed to determine the relation of these 2 fish-oil effects. In
      study 1, 54 overweight subjects consumed 3.1 g (n-3) PUFA daily. In study 2,
      which involved 42 overweight patients with type 2 diabetes, 20 subjects consumed
      (n-3) PUFA, whereas 22 others ingested a preparation rich in (n-6) PUFA. Tissue
      factor-induced thrombin generation (thrombin potential) was determined as an
      integrated measure of plasma coagulant activity. In both studies, multivariate
      analysis indicated a strong clustering of fasting concentrations of
      triacylglycerols, prothrombin, factor V, factor VII, and factor X with one
      another at baseline. This cluster of factors determined partly the
      interindividual variation in thrombin generation, of which prothrombin and
      triacylglycerol concentrations were the main determinants. In both healthy
      subjects and diabetes patients, high triacylglycerol concentrations (>1.69
      mmol/L) at baseline were closely linked to a strong fish oil-induced lowering of
      triacylglycerol and coagulation factor V, VII, and X concentrations, and thrombin
      generation. We conclude that high fasting triacylglycerol concentrations predict
      high procoagulant activity and a lowering of thrombin potential with dietary fish
      oil.

PMID- 17182794
TI  - Copper deficiency decreases complex IV but not complex I, II, III, or V in the
      mitochondrial respiratory chain in rat heart.
AB  - It has been documented that dietary copper (Cu) deficiency impairs mitochondrial
      respiratory function, which is catalyzed by 5 membrane-bound multiple protein
      complexes. However, there are few reports on the simultaneous analysis of Cu
      effect on the subunit protein expression on all 5 protein complexes. The present
      study was undertaken to determine the effect of Cu deficiency on each
      mitochondrial respiratory complex's protein expression in rat heart tissue with
      western-blot analysis. Male Sprague-Dawley rats were fed diets that were either
      Cu adequate (6.0 microg Cu/g diet, n = 5) or Cu deficient (0.3 microg Cu/g diet,
      n = 5) for 5 wk. The monoclonal antibody-based western-blot analysis suggested
      that the protein levels of 39-kDa and 30-kDa subunits in complex I; 70-kDa and 30
      kDa subunits in complex II; core I and core II subunits in complex III; and alpha
      and beta subunits of F1 complex in complex V in both high-salt buffer (HSB) and
      low-salt buffer (LSB) protein fractions from heart tissue of Cu-deficient rats
      did not differ from those of Cu-adequate rats. However, the protein level of
      cytochrome c oxidase (CCO) subunit (COX) I, COX Vb, and COX VIb subunits in
      complex IV (CCO) in both HSB and LSB protein fractions from heart tissue of Cu
      deficient rats was lower than those of Cu-adequate rats. Collectively, these data
      demonstrate that Cu deficiency decreases each tested subunit protein expression
      of complex IV but not those of complex I, II, III, and V in mitochondrial
      respiratory complexes.

PMID- 17182795
TI  - Reduction in 7,12-dimethylbenz[a]anthracene-induced hepatic cytochrome-P450 1A1
      expression following soy consumption in female rats is mediated by degradation of
      the aryl hydrocarbon receptor.
AB  - Consumption of a soy diet has been found to reduce cancer incidence in animals
      and is associated with reduced cancer risk in humans. In this study, the effect
      of consuming soy protein isolate (SPI) on the aryl hydrocarbon receptor (AhR)
      mediated signaling pathway was investigated. Female Sprague-Dawley rats were fed
      AIN-93G diets with (+) or without (-) SPI-bound phytochemicals or casein (CAS)
      protein and gavaged orally with 7,12-dimethylbenz[a]anthracene (DMBA) or sesame
      oil. We found reduced (P < 0.05) DMBA-induced hepatic cytochrome-P450 1A1
      (CYP1A1) activity, apoprotein, and mRNA expression along with the reduced binding
      of AhR-AhR nuclear translocator complex to CYP1A1 gene promoter in SPI(+)-fed
      rats compared with CAS- or SPI(-)-fed rats. Basal AhR protein expression was
      lower (P < 0.05) in SPI(+)-fed rats compared with CAS- or SPI(-)-fed groups. AhR
      levels were reduced (P < 0.05) after rats were fed SPI(+) for >20 d. Experiments
      in which SPI(+)-fed rats were weaned to CAS diets demonstrated that AhR reduction
      by SPI(+) is not imprinted metabolically. To determine the molecular mechanisms
      of SPI(+)-mediated AhR reduction, an ex vivo model was developed using FGC-4
      cells treated with serum from CAS- or SPI(+)-fed rats. SPI(+) serum treatment of
      FGC-4 cells reduced AhR expression and DMBA-induced CYP1A1 expression (P < 0.05).
      The reduction in AhR expression was in part due to the shorter half-life of AhR
      protein. Our findings suggest that the cancer preventive effect of soy-based
      diets is mediated in part by reduction in AhR protein level posttranslationally,
      which reduces procarcinogen-induced CYP1A1 induction and metabolic activation.

PMID- 17182796
TI  - Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung
      fibroblasts.
AB  - Four of the 5 biotin-dependent carboxylases (BDC) are in the mitochondria. BDC
      replace intermediates in the Krebs [tricarboxylic acid (TCA)] cycle that are
      regularly removed for the synthesis of key metabolites such as heme or amino
      acids. Heme, unlike amino acids, is not recycled to regenerate these
      intermediates, is not utilized from the diet, and must be synthesized in situ. We
      studied whether biotin deficiency (BD) lowers heme synthesis and whether
      mitochondria would be disrupted. Biotin-deficient medium was prepared by using
      bovine serum stripped of biotin with charcoal/dextran or avidin. Biotin-deficient
      primary human lung fibroblasts (IMR90) lost their BDC and senesced before biotin
      sufficient cells. BD caused heme deficiency; there was a decrease in heme content
      and heme synthesis, and biotin-deficient cells selectively lost mitochondrial
      complex IV, which contains heme-a. Loss of complex IV, which is part of the
      electron transport chain, triggered oxidant release and oxidative damage,
      hallmarks of heme deficiency. Restoring biotin to the biotin-deficient medium
      prevented the above changes. Old cells were more susceptible to biotin shortage
      than young cells. These findings highlight the biochemical connection among
      biotin, heme, and iron metabolism, and the mitochondria, due to the role of
      biotin in maintaining the biochemical integrity of the TCA cycle. The findings
      are discussed in relation to aging and birth defects in humans.

PMID- 17182797
TI  - Activation of caspase-8 contributes to 3,3'-Diindolylmethane-induced apoptosis in
      colon cancer cells.
AB  - 3,3'-Diindolylmethane (DIM) is the major in vivo product of acid-catalyzed
      oligomerization of indole-3-carbinol, which is a promising anticancer agent
      present in cruciferous vegetables and has itself been reported to have
      anticarcinogenic properties. This study examined DIM-mediated regulation of
      apoptosis in the HCT116 (wild-type p53) and HT-29 (mutant p53) human colon cancer
      cell lines. DIM (0-30 micromol/L) substantially decreased the number of viable
      cells and induced apoptosis of HCT116 and HT-29 cells in a concentration
      dependent manner. Western-blot analyses of total cell lysates revealed that DIM
      increased the activation of caspase-3, -7, -8, and -9 and enhanced poly(ADP
      ribose) polymerase cleavage in both HCT116 and HT-29 cells. In addition, DIM
      increased the translocation of cytochrome c and Smac/Diablo from the mitochondria
      to the cytoplasm. In concert with the caspase-8 activation by DIM, increased
      levels of Fas and truncated Bid were observed. DIM did not affect the protein
      levels of p53, Bcl-2, Bax, or Fas ligand (FasL) in HCT116 cells. In HT-29 cells,
      however, DIM decreased Bcl-2 levels, although the protein levels of Bax or FasL
      were not affected. The caspase-8 inhibitor Z-IETD-FMK attenuated the DIM-induced
      apoptosis, indicating that increased activation of this enzyme contributed to the
      increase in p53-independent apoptosis that was observed in colon cancer cells. We
      have demonstrated that DIM induces apoptosis in colon cancer cells, providing
      insights into the mechanisms underlying its antitumorigenic activities.

PMID- 17182798
TI  - Molybdenum intake influences molybdenum kinetics in men.
AB  - The objectives of this study were to determine physiologic adaptations that occur
      when humans are exposed to a wide range of molybdenum intake levels and to
      identify the pathways that are influenced by dietary intake. Four males consumed
      each of 5 daily molybdenum intakes of 22, 72, 121, 467, and 1490 microg/d (0.23,
      0.75, 1.3, 4.9, and 15.5 micromol/d) for 24 d each. During each treatment period,
      oral and intravenous doses of (100)Mo and (97)Mo were administered. Serial
      plasma, urine, and fecal samples were analyzed for labeled and unlabeled
      molybdenum. Compartmental modeling was used to determine rates of distribution
      and elimination at each dietary intake level. Three pathways were sensitive to
      daily molybdenum intake. With increasing intake, absorption and urinary
      molybdenum excretion increased, whereas the fraction deposited in tissues
      decreased. Kinetic analysis suggested a daily intake of 115-120 microg/d (1.20
      1.25 micromol/d) would maintain initial plasma molybdenum levels at their
      prestudy values and that their prestudy dietary intake was well above the
      Recommended Dietary Allowance of 45 microg/d. The physiological adaptations to
      changing intake that the model demonstrated may help prevent molybdenum
      deficiency and toxicity.

PMID- 17182799
TI  - Dietary supplementation of high levels of saturated and monounsaturated fatty
      acids to ewes during late gestation reduces thermogenesis in newborn lambs by
      depressing fatty acid oxidation in perirenal brown adipose tissue.
AB  - We hypothesized that dietary supplementation of (n-6) plus (n-3) PUFA during late
      gestation would increase uncoupling protein-1 (UCP1) gene expression and thereby
      increase thermogenic capacity of newborn lambs. Thirty twin-bearing ewes were fed
      rumen-protected fat (2, 4, or 8%) high in saturated and monounsaturated fatty
      acids (SMFA) or high in (n-6) and (n-3) PUFA. Lambs (n = 7-10 per ewe treatment
      group) were placed in a cold chamber at 0 degrees C for 2 h. Rectal temperature
      was higher at birth and increased more with cold exposure in lambs from ewes fed
      2 or 4% supplemental fat than in lambs from ewes fed 8% SMFA (fat type x fat
      level interaction, P = 0.001). Cytochrome c oxidase activity was greatest in
      brown adipose tissue (BAT) lambs from ewes fed 2% SMFA or 4% PUFA (fat type x fat
      level interaction, P = 0.01). BAT of lambs from ewes fed 2 or 4% PUFA had nearly
      7-fold more (P = 0.05) UCP1 mRNA than BAT of lambs from ewes fed 8% PUFA. UCP1
      expression decreased by over 80% by 24 h of age. Supplementation of 8% fat tended
      to depress palmitate esterification into lipids (P = 0.07) and decreased
      palmitate oxidation (P = 0.003) in lamb BAT in vitro, especially in those lambs
      from ewes fed 8% SMFA. Thus, supplementing the diets of ewes with 8% SMFA
      depressed cold tolerance in newborn lambs, which was reflected in their decreased
      ability to oxidize fatty acids in vitro.

PMID- 17182800
TI  - Monocarboxylate transporter 1 mediates DL-2-Hydroxy-(4-methylthio)butanoic acid
      transport across the apical membrane of Caco-2 cell monolayers.
AB  - The methionine hydroxy analogue DL-2-hydroxy-(4-methylthio)butanoic acid (DL-HMB)
      is a supplementary source of methionine commonly added to commercial animal diets
      to satisfy the total sulfur amino acid requirement. In this study, we
      characterized DL-HMB transport across the apical membrane of Caco-2 cells to
      identify the transport mechanism involved in the intestinal absorption of this
      methionine source. DL-HMB transport induced a significant decrease in
      intracellular pH (pH(i)) and was inhibited in the presence of the protonophore
      carbonyl cyanide 4-(trifluoromethoxy)-phenylhydrazone. Moreover, both Na(+)
      removal and 5-(N-ethyl-N-isopropyl)amiloride, an inhibitor of apical Na(+)/H(+)
      exchanger (NHE3), significantly reduced substrate uptake and pH(i) recovery,
      suggesting cooperation between H(+)-dependent DL-HMB transport and NHE3 activity.
      cis-Inhibition experiments with L-Ala, beta-Ala, D-Pro, betaine, or glycyl
      sarcosine excluded the participation of systems proton amino acid transporter 1
      and peptide transporter 1. In contrast, alpha-cyano-4-hydroxycinnamate,
      phloretin, L-lactate, beta-hydroxybutyrate, butyrate, and pyruvate, inhibitors
      and substrates of monocarboxylate transporter 1 (MCT1), significantly reduced DL
      HMB uptake. Dixon plot analysis of L-lactate transport in the presence of DL-HMB
      revealed a competitive interaction (inhibition constant, 17.5 +/- 0.11 mmol/L),
      confirming the participation of system MCT1. The kinetics of DL-HMB uptake was
      described by a model involving passive diffusion and a single low-affinity, high
      capacity transport mechanism (K(D), 1.9 nL/microg protein; K(m), 13.1 +/- 0.04
      mmol/L; and V(max), 43.6 +/- 0.14 pmol/microg protein) compatible with MCT1
      kinetic characteristics. In conclusion, the methionine hydroxy analogue is
      transported in Caco-2 cell apical membrane by a transport mechanism with
      functional characteristics similar to those of MCT1.

PMID- 17182801
TI  - Coadministration of ornithine and alpha-ketoglutarate is no more effective than
      ornithine alone as an arginine precursor in piglets enterally fed an arginine
      deficient diet.
AB  - Simultaneous administration of alpha-ketoglutarate and ornithine, in a 1:2 molar
      ratio, may improve the effectiveness of ornithine as an arginine precursor in
      neonatal piglets by shifting ornithine metabolism away from oxidation and toward
      the synthesis of arginine and other metabolically important compounds. To study
      this proposed mechanism, enterally fed piglets were allocated to receive 1 of 4
      diets for 5 d: an arginine-deficient [1.2 mmol/(kg . d) arginine] diet (basal),
      or the basal diet supplemented with either alpha-ketoglutarate [4.6 mmol/(kg x
      d)] (+alpha-KG), ornithine [9.2 mmol/(kg x d)] (+Orn), or both ornithine and
      alpha-ketoglutarate (+alpha-KG/+Orn, molar ratio 1:2). Primed, constant infusions
      of [1-(14)C]ornithine given both intragastrically and intraportally were used to
      measure ornithine kinetics and determine the role of first-pass intestinal
      metabolism in ornithine metabolism. Whole body arginine and glutamate kinetics
      were measured using a primed, constant intragastric infusion of [guanido
      (14)C]arginine and [3,4-(3)H]glutamate. The diets did not affect plasma arginine
      or ammonia concentrations, arginine flux, or arginine synthesis from ornithine.
      Therefore, arginine synthesis was not increased by the simultaneous infusion of
      ornithine and alpha-ketoglutarate. Piglets that received dietary ornithine had a
      2-fold greater rate of proline synthesis from ornithine (P < 0.05) and oxidized a
      greater (P < 0.05) portion of the infused ornithine than piglets in the basal and
      +alpha-KG groups. Overall, ornithine addition to an arginine deficient diet had a
      greater effect on ornithine and arginine metabolism than the addition of alpha
      ketoglutarate. First-pass intestinal metabolism was critical for ornithine
      synthesis and conversion to other metabolites but not for ornithine oxidation.

PMID- 17182802
TI  - Chronic vitamin A status and acute repletion with retinyl palmitate are
      determinants of the distribution and catabolism of all-trans-retinoic acid in
      rats.
AB  - The relation between vitamin A (VA) nutritional status and the metabolism of all
      trans-retinoic acid (RA) is not well understood. In this study, we determined the
      tissue distribution and metabolism of a test dose of [(3)H]-RA in rats with
      graded, diet-dependent, differences in VA status. The design included 3 groups,
      designated VA-deficient, VA-marginal, and VA-adequate, with liver total retinol
      concentrations of 9.7, 35.7 and 359 nmol/g, respectively, (P < 0.05), and an
      additional group of VA-deficient rats treated with a single oral dose of retinyl
      palmitate (RP) 20 h before the injection of [(3)H]-RA. Plasma, liver, lung, and
      small intestines, collected 30 min after [(3)H]-RA, were analyzed for total (3)H,
      unmetabolized [(3)H]-RA, polar organic-phase metabolites of [(3)H]-RA, and
      aqueous phase [(3)H]-labeled metabolites. In all groups, [(3)H]-RA was rapidly
      removed from plasma and concentrated in the liver. VA deficiency did not prevent
      the oxidative metabolism of RA. Nevertheless, the quantity of [(3)H]-RA
      metabolites in plasma and the ratio of total [(3)H]-polar metabolites to
      unmetabolized [(3)H]-RA in liver varied directly with VA status (VA-adequate > VA
      marginal > VA-deficient, P < 0.05). Moreover, supplementation of VA-deficient
      rats with RP reduced the metabolism of [(3)H]-RA, similar to that in VA-adequate
      or VA-marginal rats. Liver retinol concentration, considered a proxy for VA
      status, was correlated (P < 0.05) with [(3)H]-RA metabolites in liver (R(2) =
      0.54), plasma (R(2) = 0.44), lung (R(2) = 0.40), intestine (R(2) = 0.62), and all
      combined (R(2) = 0.655). Overall, the results demonstrate close linkage between
      dietary VA intake, hepatic storage of VA, and the degradation of RA and suggest
      that measuring plasma retinoid metabolites after a dose of RA may provide insight
      into the metabolism of this bioactive retinoid by visceral organs.

PMID- 17182803
TI  - Trans-10 octadecenoic acid does not reduce milk fat synthesis in dairy cows.
AB  - Diet-induced milk fat depression (MFD) involves the interrelation between rumen
      fermentation and mammary synthesis of milk fat, and the reduction in milk fat
      coincides with a marked increase in the trans-10 18:1 content of milk fat. Our
      objective was to directly examine the effect of trans-10 18:1 on milk fat
      synthesis in dairy cows. Three mid-lactation cows were used in a 3 x 3 Latin
      square design; treatments were abomasal infusion of: 1) ethanol (control); 2)
      trans-10 18:1 (t10); and 3) trans-10, cis-12 conjugated linoleic acid (CLA;
      positive control). The t10 and CLA supplements (>90% purity) were infused for 4 d
      and provided 42.6 and 4.3 g/d of trans-10 18:1 and trans-10, cis-12 CLA,
      respectively. Milk yield, feed intake, milk protein, and milk lactose were
      unaffected by treatment. Compared with the control, the t10 treatment had no
      effect on milk fat synthesis, whereas the CLA treatment resulted in a 27 and 24%
      reduction in milk fat content and yield, respectively. The transfer efficiency of
      the abomasally infused trans-10 18:1 and trans-10, cis-12 CLA into milk fat was
      15 +/- 1 and 23 +/- 5% (means +/- SD), respectively. Overall, trans-10 18:1 had
      no effect on milk fat synthesis when abomasally infused at approximately 43 g/d,
      although it was taken up by the mammary glands and incorporated into milk fat.
      Therefore, our results offer no support for the concept that changes in rumen
      production of trans-10 18:1 within the physiological range play a role in the
      regulation of fatty acid synthesis during diet-induced MFD.

PMID- 17182804
TI  - Dietary oxidized fat prevents ethanol-induced triacylglycerol accumulation and
      increases expression of PPARalpha target genes in rat liver.
AB  - Alcoholic fatty liver results from an impaired fatty acid catabolism due to
      blockade of PPARalpha and increased lipogenesis due to activation of sterol
      regulatory element-binding protein (SREBP)-1c. Because both oxidized fats (OF)
      and conjugated linoleic acids (CLA) have been demonstrated in rats to activate
      hepatic PPARalpha, we tested the hypothesis that these fats are able to prevent
      ethanol-induced triacylglycerol accumulation in the liver by upregulation of
      PPARalpha-responsive genes. Forty-eight male rats were assigned to 6 groups and
      fed isocaloric liquid diets containing either sunflower oil (SFO) as a control
      fat, OF prepared by heating of SFO, or CLA, in the presence and absence of
      ethanol, for 4 wk. Administration of ethanol lowered mRNA concentrations of
      PPARalpha and the PPARalpha-responsive genes medium chain acyl-CoA dehydrogenase,
      long chain acyl-CoA dehydrogenase, acyl-CoA oxidase, carnitine palmitoyl-CoA
      transferase I, and cytochrome P450 4A1 and increased triacylglycerol
      concentrations in the liver (P < 0.05). OF increased hepatic mRNA concentrations
      of PPARalpha-responsive genes and lowered hepatic triacylglycerol concentrations
      compared with SFO (P < 0.05) whereas CLA did not. Rats fed OF with ethanol had
      similar mRNA concentrations of PPARalpha-responsive genes and similar
      triacylglycerol concentrations in the liver as rats fed SFO or CLA without
      ethanol. In contrast, hepatic mRNA concentrations of SREBP-1c and fatty acid
      synthase were not altered by OF or CLA compared with SFO. This study shows that
      OF prevents an alcohol-induced triacylglycerol accumulation in rats possibly by
      upregulation of hepatic PPARalpha-responsive genes involved in oxidation of fatty
      acids, whereas CLA does not exert such an effect.

PMID- 17182805
TI  - Moderate consumption of olive oil by healthy European men reduces systolic blood
      pressure in non-Mediterranean participants.
AB  - We evaluated the effects of a moderate consumption of olive oil on lipid profile,
      BMI, and blood pressure (BP) in a group of 160 healthy men from non-Mediterranean
      regions [Northern Europe (n = 50; Finland and Denmark) and Central Europe (n =
      60; Germany)] and Mediterranean regions [Southern Europe (n = 45; Italy and
      Spain)]. The study was a randomized, cross-over trial with 3 intervention periods
      of 3 wk and 2 wash-out periods of 2 wk. At the intervention periods, 3 similar
      olive oils (25 mL/d), differing only in their phenolic concentration, were
      administered to the healthy volunteers. Plasma oleic acid levels increased 2-3%
      (P < 0.05) in men from populations with lower habitual olive oil intakes
      (Northern and Central Europe). General linear models showed that the
      administration of the sequence of the 3 olive oils was responsible for a 3%
      decrease in systolic BP (SBP) (P < 0.05), but not in diastolic BP, in the non
      Mediterranean subjects. Multivariate analysis indicated that the lipid profile
      did not change in either Mediterranean or non-Mediterranean men due to the olive
      oil intervention. The results of this study suggest that a moderate consumption
      of olive oil may be used as an effective tool to reduce SBP of healthy men who do
      not typically consume a Mediterranean diet. However, additional longer trials are
      necessary for confirmation.

PMID- 17182806
TI  - Iron absorption is more closely related to iron status than to daily iron intake
      in 12- to 48-mo-old children.
AB  - Few studies have evaluated iron absorption in small children after the first year
      of life. Our objectives were to examine the relations among iron intake, iron
      absorption, and iron status in a group of healthy children. We studied 28
      children, ages 12 to 48 mo, after a 7-d home adaptation to a diet representative
      of their usual daily mineral intake. A multi-tracer stable isotope study was
      performed to assess iron absorption both from a meal ((58)Fe) and from a
      reference iron dose ((57)Fe) given with ascorbic acid without a meal. Iron intake
      was 6.9 +/- 2.4 mg, approximately the 35th percentile of typical U.S. intakes.
      Absorption of (58)Fe was related to serum ferritin (r(2) = 0.319, P = 0.0018) and
      more so to reference dose iron absorption (r(2) = 0.653, P < 0.0001). Iron
      absorption was negatively correlated with zinc intake (r(2) = 0.090, P = 0.0049)
      but was not correlated with iron intake (P = 0.20). However, zinc intake was not
      correlated with measures of iron status, including reference dose iron absorption
      and serum ferritin (r(2) < 0.1, P > 0.25). Total absorbed iron was similar to
      needs estimated by the Institute of Medicine. We conclude that iron absorption in
      young children is more closely related to iron status than to iron intake.
      Reference dose iron absorption may be superior to serum ferritin as a surrogate
      measure for iron status in this age group. Although zinc intake may affect iron
      absorption from a meal, it does not appear to have a detectable effect on overall
      iron status in otherwise well-nourished children.

PMID- 17182807
TI  - Development and validation of a food frequency questionnaire for the assessment
      of dietary total antioxidant capacity.
AB  - The total antioxidant capacity (TAC) of the diet may be an important tool to
      monitor the protective effect of plant foods in epidemiological studies. We
      developed a semi-quantitative FFQ for the assessment of dietary TAC by 3
      different assays, i.e., Trolox equivalent antioxidant capacity (TEAC), total
      radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant
      power (FRAP). The FFQ consists of 53 questions about the major sources of dietary
      TAC in Northern Italy and was validated against a 3-d weighed food record (3D-WR)
      in 285 individuals (159 males and 126 females) aged 35-88 y and living in the
      province of Parma (Italy). Plasma TAC was also evaluated in a subgroup of
      subjects using the TEAC and FRAP assays. The FFQ was associated with 3D-WR
      (quadratic-weighted kappa = 0.49 for TEAC, 0.53 for TRAP, and 0.49 for FRAP; P <
      0.0001) and proved reasonably accurate to classify individuals into quartiles of
      TAC intake. The FFQ had a good repeatability when readministered after 1 y in 55
      subjects (quadratic-weighted kappa for intertertile agreement = 0.66 for TEAC,
      0.70 for TRAP and 0.68 for FRAP; P < 0.0001). With both dietary instruments, the
      main contributors to TAC intake were coffee and tea in women and alcoholic
      beverages in men, followed by fruits and vegetables in both sexes. Plasma TAC and
      dietary TAC were not associated. In conclusion, our FFQ has the potential for
      being used to rank subjects on the basis of their antioxidant intake as
      determined by dietary TAC in large epidemiological studies. The FFQ should be
      validated in external populations before being used for research purposes.

PMID- 17182808
TI  - Dietary patterns throughout adult life are associated with body mass index, waist
      circumference, blood pressure, and red cell folate.
AB  - Dietary patterns are important in the prevention of chronic disease; however,
      there are few studies that include repeat measures of dietary patterns. The
      objective of this study was to assess the relations between dietary patterns
      during adult life (at ages 36, 43, and 53 y) and risk factors for chronic disease
      at age 53 y. Participants of a longitudinal study of health completed a 5-d food
      diary at 3 occasions during adult life (n = 1265). Factor analysis was used to
      identify dietary patterns and a pattern score was calculated from the consumption
      of the food items in each dietary pattern. Means and 95% CI for dietary pattern
      scores were calculated for each risk factor category using random effects models
      adjusted for socio-demographic and health-related behaviors. In women, the fruit,
      vegetables, and dairy pattern was inversely associated with BMI (P < 0.004),
      waist circumference (P = 0.0007), blood pressure (P = 0.02), and was positively
      associated with red cell folate (P < 0.03). The ethnic foods and alcohol pattern
      was also inversely associated with blood pressure (P = 0.008), whereas the meat,
      potatoes and sweet foods pattern was positively associated with glycated
      hemoglobin (P = 0.01). In men, a mixed pattern was inversely associated with
      waist circumference (P = 0.02) and blood pressure (P = 0.01), whereas there were
      no significant associations with the ethnic foods and alcohol pattern. Specific
      dietary patterns throughout adult life were associated with chronic disease risk
      factors.

PMID- 17182809
TI  - Arginine does not exacerbate markers of inflammation in cocultures of human
      enterocytes and leukocytes.
AB  - Enteral arginine supplementation in the critically ill has become a matter of
      controversy. In this study, we investigated effects of the addition of 0.4 and
      1.2 mmol/L arginine in a coculture model on markers of inflammation, enterocyte
      layer integrity, and amino acid transport. In this model, a monolayer of
      intestinal epithelial cells (Caco-2) separated compartments with nonpathogenic
      Escherichia coli and mononuclear leukocytes. Activation of enterocytes and
      leukocytes was assessed by the measurement of nitric oxide, TNF-alpha, IL-6, IL
      8, IL-10, and IFN-gamma. Further outcomes were the transepithelial flux of 22
      amino acids, their catabolism, and the integrity of the enterocyte layer assessed
      as permeability of fluorescein dextran (M(r) 4400). Bacterial stimulation of
      intestinal epithelial cells enhanced the basolateral concentration of nitric
      oxide and all cytokines measured. Supplementation with arginine did not affect
      epithelial integrity, production of any of the cytokines investigated, or the
      amount of nitric oxide. The amino acid used primarily by nonstimulated intestinal
      epithelial cells cocultured with leukocytes was glutamine. Activation of IEC with
      bacteria significantly enhanced the catabolism of serine, asparagine, and lysine,
      and reduced glutamine catabolism. Addition of arginine increased ornithine
      formation and moderately reduced transepithelial transport of methionine and
      other amino acids. Hence, arginine supplementation does not interfere with
      inflammation-associated cross-talk between human enterocytes and leukocytes.
      Because it also does not seem to affect the integrity of enterocyte layers, a
      detrimental role of arginine during septic-like conditions seems unlikely.

PMID- 17182810
TI  - Adding zinc to supplemental iron and folic acid does not affect mortality and
      severe morbidity in young children.
AB  - Studies have found a substantial reduction in diarrhea and respiratory morbidity
      in young children receiving zinc supplementation. The impact of daily zinc
      supplementation administered with iron plus folic acid (IFA) in young children on
      all-cause hospitalizations and mortality in comparison with IFA alone was
      evaluated. In a double blind cluster-randomized controlled trial, 94,359 subjects
      aged 1-23 mo were administered a daily dose of zinc plus IFA or IFA alone for a
      duration of 12 mo after enrollment. The intervention group tablet contained 10 mg
      of elemental zinc, 12.5 mg of iron, and 50 microg of folic acid. The control
      group tablets were similar except that they contained a placebo for zinc. Infants
      aged <6 mo were administered half a tablet, and those older received 1 tablet
      dissolved in breast milk or water. Hospitalizations were captured by trained
      study physicians through the surveillance of 8 hospitals. Deaths and
      hospitalizations were ascertained through visits to households by study
      supervisors once every 2 mo. The overall death rates did not differ significantly
      between the 2 groups when adjusted for cluster randomization (hazard ratio =
      1.02, 95% CI 0.87, 1.19). Zinc and IFA supplementation compared with IFA alone
      did not affect adjusted hospitalization rates (overall rate ratio = 1.08, 95% CI
      0.98, 1.19; diarrhea-specific rate ratio = 1.15, 95% CI 0.99, 1.34; or pneumonia
      specific rate ratio = 1.09, 95% CI 0.94, 1.25). The lack of impact of zinc on
      mortality and hospitalization rates in this study may have been due to the use of
      lower daily zinc dosing than used in some of the morbidity prevention trials or
      from an interaction between zinc and iron, where the addition of iron may have
      adversely affected potential effects of zinc on immune function and morbidity.
      Future research should address iron and zinc interaction effects on important
      functional outcomes.

PMID- 17182811
TI  - Early iron deficiency alters sensorimotor development and brain monoamines in
      rats.
AB  - Iron deficiency in human infancy reportedly leads to developmental delays and
      changes in neurobiology that may be irreversible. Using a rodent model, the
      present study examined whether dietary iron deficiency late in pregnancy and
      during lactation alters sensorimotor development and brain monoaminergic systems.
      Rats were assigned to 1 of 4 dietary treatments during gestation and lactation:
      1) iron sufficient control; 2) prenatal iron deficiency beginning on gestational
      d 15 (G15); 3) postnatal iron deficiency beginning on postnatal d 4 (P4); 4) iron
      deficiency beginning on G15 followed by an iron sufficient diet on P4.
      Developmental milestones, open field behavior, brain iron and proteins,
      monoamines, and their transporters were evaluated between P6 and P21. Only G15
      iron deficient rats had greater dopaminergic activity than controls as indicated
      by increased tyrosine hydroxylase levels, phosphorylated tyrosine hydroxylase
      levels, and cellular dopamine in prefrontal cortex and striatum at P15. These
      rats also showed delayed eye opening, ear development, and reduced locomotor
      activity. Iron repletion at P4 returned most measures to control levels by the
      time of weaning. Postnatal iron deficiency reduced striatal and ventral midbrain
      iron as well as cellular dopamine levels in prefrontal cortex and striatum at
      P21. Developmental delays in ear development and achievement in bar holding and
      surface righting also resulted from postnatal iron deficiency. These results
      indicate that iron deficiency begun at G15 affects early dopamine neurobiology,
      the development of specific developmental milestones, and behavior in preweaned
      rats.

PMID- 17182812
TI  - Maternal parity and diet (n-3) polyunsaturated fatty acid concentration influence
      accretion of brain phospholipid docosahexaenoic acid in developing rats.
AB  - The long-chain PUFA, docosahexaenoic acid [22:6(n-3), DHA], a major component of
      neuronal membrane phospholipids, accumulates in brain during late prenatal and
      early neonatal development and is essential for optimal attentional and cognitive
      function. Because all nutrition is supplied to the developing fetus/neonate by
      the mother and maternal DHA status is affected by parity, this study examined the
      effects of maternal diet and parity on DHA accretion in the developing brain.
      Whole brain total phospholipid fatty acid composition was determined by TLC and
      GC in weanling male Long-Evans rats (n = 5) from the 1st, 2nd, 3rd, or 4th
      litters of dams fed diets containing alpha-linolenic acid (ALA), containing ALA
      and preformed DHA (ALA + DHA), or lacking ALA (low-ALA). First-litter low-ALA
      offspring exhibited a decrease in phospholipid fatty acid DHA content to 68% of
      1st-litter ALA pups. DHA in 2nd-litter low-ALA pups was further decreased to 55%
      of 1st-litter ALA pups, but further decreases were not observed in subsequent
      litters. DHA levels increased 15-20% in 2nd to 4th-litter ALA + DHA pups and 11%
      in 4th-litter ALA pups compared with 1st-litter ALA pups. These findings
      demonstrate that maternal diet and parity interact to affect offspring brain DHA
      status and suggest that maternal multiparity may place offspring at greater risk
      of decreased accretion of brain DHA if the maternal diet contains insufficient (n
      3) PUFA.

PMID- 17182813
TI  - Specific brain regions of female rats are differentially depleted of
      docosahexaenoic acid by reproductive activity and an (n-3) fatty acid-deficient
      diet.
AB  - Low tissue levels of (n-3) PUFA, particularly docosahexaenoic acid [DHA, 22:6(n
      3)], are implicated in postpartum depression. Brain DHA content is depleted in
      female rats undergoing pregnancy and lactation when the diet supplies inadequate
      (n-3) PUFA. In this study, the effects of DHA depletion as a result of
      reproductive activity and an (n-3) PUFA-deficient diet were examined in 8
      specific brain regions of female rats after undergoing 2 sequential reproductive
      cycles. Virgin females, fed the alpha-linolenic acid (ALA)-containing or
      deficient (low-ALA) diets for a commensurate duration (13 wk) served as a control
      for reproduction. Total phospholipid composition of each brain region was
      determined at weaning (postnatal d 21) by TLC/GC. The regional PUFA composition
      of ALA virgins was similar to that previously measured in male rats. All brain
      regions examined were affected by reproductive activity and/or the low-ALA diet;
      however, the magnitude of the loss of DHA and compensatory incorporation of
      docosapentaenoic acid [(n-6) DPA, 22:5(n-6)] varied among brain regions. In low
      ALA parous dams, frontal cortex (77% of ALA virgin) and temporal lobe (83% of ALA
      virgin), regions involved in cognition and affect, were among those exhibiting
      the greatest depletion of DHA. Caudate-putamen also exhibited significant
      depletion of DHA (82% of ALA virgin), whereas only (n-6) DPA levels were altered
      in ventral striatum, hypothalamus, hippocampus, and cerebellum. This pattern of
      changes in regional DHA and (n-6) DPA content suggests that specific neuronal
      systems may be differentially affected by depletion of brain DHA in the
      postpartum organism.

PMID- 17182814
TI  - A mathematical model of zinc absorption in humans as a function of dietary zinc
      and phytate.
AB  - The quantities of zinc and phytate in the diet are the primary factors
      determining zinc absorption. A mathematical model of zinc absorption as a
      function of dietary zinc and phytate can be used to predict dietary zinc
      requirements and, potentially, enhance our understanding of zinc absorption. Our
      goal was to develop a model of practical and informative value based on
      fundamental knowledge of the zinc absorption process and then fit the model to
      selected published data to assess its validity and estimate parameter values. A
      model of moderate mathematical complexity relating total zinc absorption to total
      dietary zinc and total dietary phytate was derived and fit to 21 mean data from
      whole day absorption studies using nonlinear regression analysis. Model validity,
      goodness of fit, satisfaction of regression assumptions, and quality of the
      parameter estimates were evaluated using standard statistical criteria. The fit
      had an R(2) of 0.82. The residuals were found to exhibit a normal distribution,
      constant variance, and independence. The parameters of the model, A(MAX), K(R),
      and K(P), were estimated to have values of 0.13, 0.10, and 1.2 mmol/d,
      respectively. Several of these estimates had wide CI attributable in part to the
      small number and the scatter of the data. The model was judged to be valid and of
      immediate value for studying and predicting absorption. A version of the model
      incorporating a passive absorption mechanism was not supported by the available
      data.

PMID- 17182816
TI  - Comparison of the WHO child growth standards and the CDC 2000 growth charts.
AB  - The evaluation of child growth trajectories and the interventions designed to
      improve child health are highly dependent on the growth charts used. The U.S. CDC
      and the WHO, in May 2000 and April 2006, respectively, released new growth charts
      to replace the 1977 NCHS reference. The WHO charts are based for the first time
      on a prescriptive, prospective, international sample of infants selected to
      represent optimum growth. This article compares the WHO and CDC curves and
      evaluates the growth performance of healthy breast-fed infants according to both.
      As expected, there are important differences between the WHO and CDC charts that
      vary by age group, growth indicator, and specific Z-score curve. Differences are
      particularly important during infancy, which is likely due to differences in
      study design and characteristics of the sample, such as type of feeding. Overall,
      the CDC charts reflect a heavier, and somewhat shorter, sample than the WHO
      sample. This results in lower rates of undernutrition (except during the first 6
      mo of life) and higher rates of overweight and obesity when based on the WHO
      standards. Healthy breast-fed infants track along the WHO standard's weight-for
      age mean Z-score while appearing to falter on the CDC chart from 2 mo onwards.
      Shorter measurement intervals in the WHO standards result in a better tool for
      monitoring the rapid and changing rate of growth in early infancy. Their adoption
      would have important implications for the assessment of lactation performance and
      the adequacy of infant feeding and would bring coherence between the tools used
      to assess growth and U.S. national guidelines that recommend breast-feeding as
      the optimal source of nutrition during infancy.

PMID- 17182817
TI  - Field-testing the WHO child growth standards in four countries.
AB  - In April 2006 the WHO released a set of growth standards for children from birth
      to the age of 5 y. Prior to their release, the standards were field-tested in 4
      countries. The main objective was to compare children's length/height-for-age and
      weight-for-length/height based on the new standards with clinician assessments of
      the same children. The study sampled children <5-y-old attending well-child
      clinics in 2 affluent populations (Argentina and Italy) and 2 less-affluent ones
      (Maldives and Pakistan). Length/height and weight were measured by doctors and
      epidemiologists who also recorded a clinical assessment of each child's
      length/height in relation to age and weight relative to length/height.
      Anthropometric indicators of nutritional status were generated based on the WHO
      standards. As expected, Pakistan and the Maldives had higher rates of stunting,
      wasting, and underweight than Italy and Argentina, and the reverse was true for
      overweight and obesity. Where stunting was prevalent, the children classified as
      short were a mean <-2 SD for height-for-age. In all sites, the children
      classified as thin were indeed wasted (<-2 SD for weight-for-height) and a
      positive association in trend was evident between weight-for-height and the line
      up of groups from thin to obese. The overall concordance between clinical
      assessments and the WHO standards-based indicators attested to the clinical
      soundness of the standards.

PMID- 17182818
TI  - Evaluation of the feasibility of international growth standards for school-aged
      children and adolescents.
AB  - The development of an international growth standard for the screening,
      surveillance, and monitoring of school-aged children and adolescents has been
      motivated by 2 contemporaneous events, the global surge in childhood obesity and
      the release of a new international growth standard for infants and preschool
      children by the WHO. If a prescriptive approach analogous to that taken by WHO
      for younger children is to be adopted for school-aged children and adolescents,
      several issues need to be addressed regarding the universality of growth
      potential across populations and the definition of optimal growth in children and
      adolescents. A working group of experts in growth and development and
      representatives from international organizations concluded that subpopulations
      exhibit similar patterns of growth when exposed to similar external conditioners
      of growth. However, based on available data, we cannot rule out that observed
      differences in linear growth across ethnic groups reflect true differences in
      genetic potential rather than environmental influences. Therefore, the sampling
      frame for the development of an international growth standard for children and
      adolescents must include multiethnic sampling strategies designed to capture the
      variation in human growth patterns. A single international growth standard for
      school-aged children and adolescents could be developed with careful
      consideration of the population and individual selection criteria, study design,
      sample size, measurements, and statistical modeling of primary growth and
      secondary ancillary data. The working group agreed that existing growth
      references for school-aged children and adolescents have shortcomings,
      particularly for assessing obesity, and that appropriate growth standards for
      these age groups should be developed for clinical and public health applications.

PMID- 17182819
TI  - Proceedings and abstracts of the International Research Conference on Food,
      Nutrition, and Cancer, July 13-14, 2006, Washington, DC, USA.

PMID- 17182820
TI  - Exercise and biomarkers for cancer prevention studies.
AB  - The International Agency for Research on Cancer estimates that 25% of cancer
      cases worldwide are caused by overweight or obesity and a sedentary lifestyle.
      These lifestyle patterns may increase cancer risk by several mechanisms including
      increased estrogens and testosterone, hyperinsulinemia and insulin resistance,
      increased inflammation, and depressed immune function. Several randomized
      clinical trials have shown that physical activity and diet interventions can
      change biomarkers of cancer risk. In a controlled physical activity trial, we
      found decreases in serum estrogen, testosterone, and insulin in overweight,
      sedentary postmenopausal women with a 1-y exercise program consisting of moderate
      intensity aerobic exercise, 45 min/d, 5 d/wk. In another controlled trial in
      middle-aged to older persons, we found that a 1-y exercise intervention of 60
      min/d, 6 d/wk, reduced colon crypt cell proliferation in men who adhered closely
      to the program. Only 1 trial, the Women's Health Initiative Dietary Modification
      Trial, has published results of a dietary intervention on breast cancer incidence
      and reported a statistically nonsignificant 9% reduction in invasive breast
      cancer incidence in postmenopausal women following a low-fat dietary pattern for
      8-12 y. Other trials under way are testing effects of weight loss, physical
      activity, and dietary patterns on other cancer biomarkers. The NCI-funded
      Transdisciplinary Research on Energetics and Cancer centers are exploring novel
      research into mechanisms linking energy balance with cancer risk and prevention.
      The worldwide trends toward increasing overweight and obesity and decreasing
      physical activity may lead to an increased incidence of several cancers unless
      other means of risk reduction counteract these effects. Thus, adoption of
      lifestyle changes by individuals and populations may have a large impact on the
      future incidence of cancer.

PMID- 17182821
TI  - Changes in dietary fat and fiber and serum hormone concentrations: nutritional
      strategies for breast cancer prevention over the life course.
AB  - The association between dietary fat intake and breast cancer risk has appeared in
      a meta-analysis of epidemiologic research, migration studies from countries of
      low to high risk for breast cancer, and animal experiments. With this background,
      dietary intervention research aims to reduce fat intake and increase fruit,
      vegetable, and fiber intake, relying on changes in hormone concentrations as
      biomarkers for reduction in risk of breast cancer. To date, this dietary
      intervention research spans the life course and has demonstrated stellar success
      in some studies but sobering results in others. The purpose of this article is to
      review the intervention research since a 1999 meta-analysis that reported reduced
      estradiol levels on a low-fat diet and to explore the lessons learned from
      intervention research on changes in dietary fat and fiber intake and serum
      hormone concentrations. Secular trends in obesity and ages at pubertal onset and
      menarche provide dynamic behavioral, genetic, and developmental challenges to the
      success of dietary prevention. The goal is to formulate an integrative approach
      to dietary intervention, taking into consideration ethnic group differences in
      energy expenditure that modulate weight and hormones influencing breast cancer
      risk over the life course.

PMID- 17182822
TI  - Why do African Americans get more colon cancer than Native Africans?
AB  - The incidence of colorectal cancer (CRC) is dramatically higher in African
      Americans (AAs) than in Native Africans (NAs) (60:100,000 vs. <1:100,000) and
      slightly higher than in Caucasian Americans (CAs). To explore whether the
      difference could be explained by interactions between diet and colonic bacterial
      flora, we compared randomly selected samples of healthy 50- to 65-y-old AAs (n =
      17) with NAs (n = 18) and CAs (n = 17). Diet was measured by 3-d recall, and
      colonic metabolism by breath hydrogen and methane responses to oral lactulose.
      Fecal samples were cultured for 7-alpha dehydroxylating bacteria and
      Lactobacillus plantarum. Colonoscopic mucosal biopsies were taken to measure
      proliferation rates. In comparison with NAs, AAs consumed more (P < 0.01) protein
      (94 +/- 9.3 vs. 58 +/- 4.1 g/d) and fat (114 +/- 11.2 vs. 38 +/- 3.0 g/d), meat,
      saturated fat, and cholesterol. However, they also consumed more (P < 0.05)
      calcium, vitamin A, and vitamin C, and fiber intake was the same. Breath hydrogen
      was higher (P < 0.0001) and methane lower in AAs, and fecal colony counts of 7
      alpha dehydroxylating bacteria were higher and of Lactobacilli were lower.
      Colonic crypt cell proliferation rates were dramatically higher in AAs (21.8 +/-
      1.1% vs. 3.2 +/- 0.8% labeling, P < 0.0001). In conclusion, the higher CRC risk
      and mucosal proliferation rates in AAs than in NAs were associated with higher
      dietary intakes of animal products and higher colonic populations of potentially
      toxic hydrogen and secondary bile-salt-producing bacteria. This supports our
      hypothesis that CRC risk is determined by interactions between the external
      (dietary) and internal (bacterial) environments.

PMID- 17182823
TI  - Inflammation, cancer, and targets of ginseng.
AB  - Chronic inflammation is associated with a high cancer risk. At the molecular
      level, free radicals and aldehydes, produced during chronic inflammation, can
      induce deleterious gene mutation and posttranslational modifications of key
      cancer-related proteins. Other products of inflammation, including cytokines,
      growth factors, and transcription factors such as nuclear factor kappaB, control
      the expression of cancer genes (e.g., suppressor genes and oncogenes) and key
      inflammatory enzymes such as inducible nitric oxide synthase and cyclooxygenase
      2. These enzymes in turn directly influence reactive oxygen species and
      eicosanoid levels. The procancerous outcome of chronic inflammation is increased
      DNA damage, increased DNA synthesis, cellular proliferation, disruption of DNA
      repair pathways and cellular milieu, inhibition of apoptosis, and promotion of
      angiogenesis and invasion. Chronic inflammation is also associated with
      immunosuppression, which is a risk factor for cancer. Current treatment
      strategies for reactive species overload diseases are frequently aimed at
      treating or preventing the cause of inflammation. Although these strategies have
      led to some progress in combating reactive species overload diseases and
      associated cancers, exposure often occurs again after eradication, treatment to
      eradicate the cause fails, or the treatment has long-term side effects.
      Therefore, the identification of molecules and pathways involved in chronic
      inflammation and cancer is critical to the design of agents that may help in
      preventing the progression of reactive species overload disease and cancer
      associated with disease progression. Here, we use ginseng as an example of an
      antiinflammatory molecule that targets many of the key players in the
      inflammation-to-cancer sequence.

PMID- 17182824
TI  - Cranberry and its phytochemicals: a review of in vitro anticancer studies.
AB  - This article reviews the existing research on the anticancer properties of
      cranberry fruit and key phytochemicals that are likely contributors to
      chemoprevention. Results from in vitro studies using a variety of tumor models
      show that polyphenolic extracts from Vaccinium macrocarpon inhibit the growth and
      proliferation of breast, colon, prostate, lung, and other tumors, as do
      flavonols, proanthocyanidin oligomers, and triterpenoids isolated from the fruit.
      The unique combination of phytochemicals found in cranberry fruit may produce
      synergistic health benefits. Possible chemopreventive mechanisms of action by
      cranberry phytochemicals include induction of apoptosis in tumor cells, reduced
      ornithine decarboxylase activity, decreased expression of matrix
      metalloproteinases associated with prostate tumor metastasis, and
      antiinflammatory activities including inhibition of cyclooxygenases. These
      findings suggest a potential role for cranberry as a dietary chemopreventive and
      provide direction for future research.

PMID- 17182825
TI  - Cytokine gene polymorphisms, cancer susceptibility, and prognosis.
AB  - IL-10 is a multifunctional cytokine with both immunosuppressive and
      antiangiogenic functions and may have both tumor-promoting and -inhibiting
      properties. A large number of polymorphisms (primarily single-nucleotide
      polymorphisms) have been identified in the IL10 gene promoter. Convincing
      evidence that certain of these polymorphisms are associated with differential
      expression of IL-10 in vitro and in some cases in vivo was obtained, and a number
      of studies investigated associations between IL10 polymorphisms and cancer
      susceptibility and prognosis. The results from 22 studies in 13 different
      malignancies are reviewed. In 17 of these studies, positive associations between
      IL10 genotype or haplotype and disease susceptibility, progression, or both were
      reported. In some of these cancers genotypes associated with low IL-10 expression
      were a risk factor for disease or disease progression, whereas in others
      genotypes associated with high IL-10 expression were a risk factor. Published
      findings in breast cancer are as yet conflicting. Most but not all of the studies
      reviewed are based on small sample sizes and a limited number of IL10
      polymorphisms. However, the preliminary data indicate that larger studies are
      required in a number of cancers to confirm initial results, extend studies to
      include more detailed genotype and haplotype analysis, and combine genotype and
      gene expression studies in the same subjects. Such studies will contribute
      significantly to our understanding of the biological role of IL-10 in cancer
      development.

PMID- 17182826
TI  - Immunomodulatory effects of (n-3) fatty acids: putative link to inflammation and
      colon cancer.
AB  - Chronic inflammation and colorectal cancer are closely linked. Although the
      overall mechanisms of inflammation-associated gastrointestinal carcinogenesis are
      complex, it is clear that antiinflammatory therapy is efficacious against
      neoplastic progression and malignant conversion. From a dietary perspective, fish
      oil containing (n-3) polyunsaturated fatty acids (PUFAs) has antiinflammatory
      properties, but for years the mechanism has remained obscure. Of relevance to the
      immune system in the intestine, we showed that (n-3) PUFA feeding alters the
      balance between CD4+ T-helper (Th1 and Th2) subsets by directly suppressing Th1
      cell development (i.e., clonal expansion). This is noteworthy because Th1 cells
      mediate inflammatory diseases and resistance to intracellular pathogens or
      allergic hypersensitivity, and Th2 cells mediate resistance to extracellular
      pathogens. Therefore, any changes induced by (n-3) PUFAs in T-cell subset balance
      and function are important because the outcome is expected to suppress the
      development of autoimmune diseases and possibly the occurrence of colon cancer.
      Precisely how the immunomodulatory effects of (n-3) PUFAs influence inflammation
      associated colonic tumor development is the subject of an ongoing investigation.

PMID- 17182827
TI  - Calcitriol and genistein actions to inhibit the prostaglandin pathway: potential
      combination therapy to treat prostate cancer.
AB  - We present an overview of the prostaglandin (PG) pathway as a novel target for
      the treatment of prostate cancer (PCa) using a combination of calcitriol and
      genistein, both of which have known antiproliferative properties. Calcitriol
      inhibits the PG pathway in PCa cells in 3 separate ways: by decreasing
      cyclooxygenase-2 (COX-2) expression, stimulating 15-hydroxyprostaglandin
      dehydrogenase (15-PGDH) expression, and decreasing EP (PGE2) and FP (PGF(2alpha))
      receptors. These actions of calcitriol result in reduced levels of biologically
      active PGE2, leading ultimately to growth inhibition of the PCa cells. We also
      demonstrate the advantages of using calcitriol in combination with genistein for
      the treatment of PCa. Genistein, a major component of soy, is a potent inhibitor
      of the activity of CYP24, the enzyme that initiates the degradation of
      calcitriol. This leads to increased half-life of bioactive calcitriol, thereby
      enhancing all of calcitriol's actions including those on the PG pathway. In
      addition to inhibiting CYP24 enzyme activity, genistein has its own independent
      actions on the PG pathway in PCa cells. Like calcitriol it inhibits COX-2
      expression and activity, leading to decreased synthesis of PGE2. It also inhibits
      the EP and FP receptors, thereby reducing the biological function of PGE2. Thus,
      the combination of calcitriol and genistein acts additively to inhibit the PG
      pathway. Both calcitriol and genistein are relatively safe and have little
      toxicity associated with their intake. We postulate that the combination of
      calcitriol and genistein is an attractive therapeutic option for the treatment of
      PCa.

PMID- 17182828
TI  - Gender-specific modulation of markers for premalignancy by nutritional soy and
      calcium in the mouse colon.
AB  - Sporadic colorectal cancer develops as a multistep process during decades of
      latency. Multiple factors, in particular nutrition, influence progression. Both
      nutritional calcium and soy are known to reduce sporadic cancer incidence. Soy
      contains high levels of phytoestrogens. Among them genistein is recognized as an
      antioxidant and cell-cycle inhibitor. However, timing and length of consumption
      of genistein as well as gender- and colon site-specific activity may result in
      beneficial or detrimental effects. We therefore evaluated the effect in mice of a
      basic AIN76A diet containing 20% soy as main protein source fed for 1 or 2
      generations. In another set of animals, normal calcium levels (0.5%) were
      replaced by low calcium (0.04%) with or without supplementation of genistein
      (0.04%). Expression of the vitamin D receptor, cyclooxygenase (COX)-2,
      proapoptotic Bak and antiapoptotic Bcl-2 protein, as well as estrogen receptor
      (ER)-alpha and ER-beta mRNA were evaluated. Results were identical whether soy
      was fed for 1 or 2 generations. Soy decreased Bak and increased COX-2 and ER
      alpha expression site-specifically in female mice. Vitamin D receptor protein was
      reduced only in males. In animals fed 0.04% dietary calcium, COX-2 protein was
      increased mainly in females, but supplementation of genistein to the diet lowered
      COX-2 expression significantly in both genders. Our results suggest that
      genistein counteracts the induction of a marker of colonic premalignancy by low
      nutritional calcium in both genders. However, soy itself enhances COX-2 and
      reduces Bak, but only in females. This suggests detrimental activity of an
      unknown component of soy triggered by a high-estrogen background.

PMID- 17182829
TI  - Methyl deficiency, alterations in global histone modifications, and
      carcinogenesis.
AB  - The methyl-deficient model of endogenous hepatocarcinogenesis in rodents is
      unique in that dietary omission rather than the addition of chemical carcinogens
      leads to tumor formation. Thus, the biochemical and molecular events predisposing
      to cancer in this model result from chronic metabolic stress and provide an ideal
      model system to study progressive alterations that occur during carcinogenesis.
      Moreover, epigenetic alterations imposed by this diet are believed to be 1 of the
      main mechanisms responsible for malignant transformation of rat liver cells. In
      this study we examined the changes in global histone modification patterns in
      liver during hepatocarcinogenesis induced by methyl deficiency. Feeding animals
      the methyl-deficient diet (MDD) led to progressive loss of histone H4 lysine 20
      trimethylation (H4K20me3), H3 lysine 9 trimethylation (H3K9me3), and histone H3
      lysine 9 (H3K9ac) and histone H4 lysine 16 (H4K16ac) acetylation. A considerable
      decrease of H4K20me3 and H3K9ac was also detected in liver tumors induced by MDD.
      In contrast, liver tumors displayed an increase in H3K9me3 and H4K16ac. To
      determine the possible mechanism of alterations of histone modifications, we
      analyzed the expression of histone-modifying enzymes in liver during
      hepatocarcinogenesis. The expression of Suv4-20h2 and RIZ1 histone
      methyltransferases (HMTs) steadily decreased along with the development of liver
      tumors and reached its lowest level in tumor tissue, whereas the expression of
      Suv39-h1 HMT and histone acetyltransferase 1 (HAT1) substantially increased in
      tumors. These results illustrate the complexity and importance of histone
      modification changes in the etiology of hepatocarcinogenesis induced by MDD.

PMID- 17182830
TI  - Dietary polyphenols may affect DNA methylation.
AB  - Certain dietary polyphenols, such as (-)-epigallocatechin 3-gallate (EGCG) from
      green tea and genistein from soybean, have been demonstrated to inhibit DNA
      methyltransferases (DNMT) in vitro. This inhibitory activity is associated with
      the demethylation of the CpG islands in the promoters and the reactivation of
      methylation-silenced genes such as p16INK4a, retinoic acid receptor beta, O6
      methylguanine methyltransferase, human mutL homolog 1, and glutathione S
      transferase-pi. These activities have been observed in human esophageal, colon,
      prostate, and mammary cancer cell lines, and the activity can be enhanced by the
      presence of histone deacetylase inhibitors or by a longer-term treatment. Many
      other polyphenolic compounds have lower activities in inhibiting DNMT. Catechol
      polyphenols may indirectly inhibit DNMT by generating S-adenosyl-L-homocysteine
      on their methylation by S-adenosyl-L-methionine. In theory, prevention or
      reversal of hypermethylation-induced inactivation of key tumor suppression genes
      or receptor genes by DNMT inhibitors could be an effective approach for cancer
      prevention. Because of the rather low bioavailability of most polyphenolic
      compounds, how much of an effect dietary polyphenols would have on DNA
      methylation in humans is not clear. The effect of normal dietary consumption of a
      single polyphenolic compound is probably insignificant. However, the combination
      of polyphenols with dietary histone deacetylase inhibitors and the additive
      effect of different dietary chemicals may produce some effects. On the other
      hand, the consumption of excessive amounts of polyphenols in dietary supplements
      may affect DNA methylation status. All these possibilities remain to be examined.

PMID- 17182831
TI  - Antioxidants suppress lymphoma and increase longevity in Atm-deficient mice.
AB  - Ataxia telangiectasia (AT), a human hereditary disorder resulting from mutations
      in the ATM gene, is characterized by a high incidence of lymphoid malignancies,
      neurodegeneration, immunodeficiency, premature aging, elevated radiosensitivity,
      and genomic instability. Evidence has been accumulating that ATM-deficient cells
      are in a continuous state of oxidative stress. A variety of markers of oxidative
      stress were detected in AT patients as well as Atm-deficient mice, used as an
      animal model of AT. Since then, it has been proposed that oxidative stress
      contributes to the clinical phenotype of AT, especially carcinogenesis and
      neurodegeneration, and several animal studies were conducted to determine whether
      exogenous antioxidants mitigate the symptoms of AT. Tempol, EUK-189, and N-acetyl
      cysteine have been tested as chemopreventive antioxidants in Atm-deficient mice.
      We review these findings, mainly focusing on the effect of N-acetyl cysteine,
      which is known as a safe and efficient drug and nutritional supplement.

PMID- 17182832
TI  - Lifestyle change including dietary fat reduction and breast cancer outcome.

PMID- 17182833
TI  - Lifestyle factors and survival in women with breast cancer.
AB  - With increasing longevity and more effective cancer therapies, the population of
      cancer survivors is increasing. For example, it is estimated that there are over
      2 million breast cancer survivors in the United States. Among cancer survivors
      and their families, there is substantial interest in whether there is anything
      that they can do beyond conventional therapy to improve their prognosis. Chief
      among these is interest in diet and use of complementary and alternative
      therapies. Despite this interest, there is surprisingly little that is known
      about the effects of these factors on cancer survival. This is in part because of
      the usual approach to research on diet and breast cancer in human populations.
      Studies that have had food and nutrition as a main interest have focused almost
      exclusively on cancer etiology and prevention; there are literally hundreds of
      such studies. Meanwhile, studies of populations after a breast cancer diagnosis
      have rarely considered lifestyle factors. Such studies have focused largely on
      therapeutics, such as effects of different chemotherapy regimens, or prognostic
      factors, such as the effects of stage of disease, hormone receptor status, or
      gene expression signatures on prognosis. To the extent that lifestyle factors
      have been a focus of cancer prognosis studies, they have often been aimed at the
      question of whether they impact quality of life, and not on whether they
      influence cancer survival or recurrence. There have been a handful of studies
      that have had lifestyle factors such as diet and physical activity as a principal
      focus. In addition to 2 randomized trials, the Women's Intervention Nutrition
      Study (WINS) and the Women's Healthy Eating and Living Study, there are at least
      5 ongoing prospective cohort studies in breast cancer survivors that have diet as
      a main focus. Although these studies differ in various aspects, they are all
      aimed at examining whether differences in diet may result in differences in
      recurrence and mortality rates. One such study, the Pathways Study, is a
      prospective cohort study that began recruitment of study participants in early
      2006. This study is unique in that it is enrolling women as soon after breast
      cancer diagnosis as is practical, whereas other studies have generally enrolled
      women after completion of adjuvant therapy or later. This and other studies
      promise to provide some of the first objective information regarding diet and
      breast cancer prognosis and serve as models for studies of diet and prognosis of
      other cancers.

PMID- 17182834
TI  - Lifestyle interventions in cancer survivors: designing programs that meet the
      needs of this vulnerable and growing population.
AB  - In the world today, there are roughly 25 million cancer survivors. Although the
      increasing numbers of survivors testifies to the success of early detection and
      treatment, there is a downside. Cancer survivors are at increased risk for second
      cancers, other forms of comorbidity (e.g., cardiovascular disease, diabetes,
      osteoporosis), and functional decline. Lifestyle factors, such as a healthy diet,
      regular exercise, and smoking cessation may prevent these conditions and improve
      survivors' quality of life. Data also are accumulating to suggest that healthful
      lifestyle practices and successful weight management may prevent progressive or
      recurrent disease. Previous surveys conducted among both adult and pediatric
      cancer survivors indicate that most survivors have high levels of interest in
      diet and exercise interventions. Additionally, survivors who smoke report high
      levels of interest in interventions aimed at smoking cessation. Many factors,
      such as intervention timing and duration and channels of delivery, must be
      carefully considered in developing interventions that best meet the needs of this
      vulnerable population. Total transparency also is necessary in reporting the
      results of trials to ensure the inclusion of information regarding proportional
      accrual, attrition, and study sample sociodemographic characteristics to move
      toward the development of interventions most likely to gain broad-scale
      acceptance and adherence. Home-based interventions that rely on telephone
      counseling, mailed materials, or computer-assisted approaches offer promising
      means of reaching the geographically dispersed population of cancer survivors.
      More research is necessary to develop interventions that can reach and
      effectively promote long-term behavior change in this ever-increasing population.

PMID- 17182835
TI  - Can biomarkers help us understand the nutritional and lifestyle factors important
      in cancer prognosis?
AB  - In attempting to discover the causes of cancer, investigators have recognized
      that biomarkers can confirm biological plausibility, enhance relative risks, and
      serve as surrogate endpoints in observational and intervention studies. In the
      arena of cancer survival, the potential value of biomarkers is increasingly
      appreciated. A broad range of histological, cellular, and molecular markers have
      been identified among persons diagnosed with cancer. Molecular and cellular
      markers are being used to stage disease, predict prognosis, and target
      therapeutic interventions. Biomarkers in survivors can also help us to understand
      factors that influence prognosis by both elucidating pertinent biological
      pathways and sharpening risk estimates. However, as in the case of incident
      cancer, the use of biomarkers as surrogate endpoints postdiagnosis is problematic
      because of the potential existence of alternative pathways to recurrence and
      death that bypass the surrogate endpoint. In evaluating potential surrogates, an
      understanding of the causal structure underlying the interrelations of exposures,
      surrogate, and recurrence or death is essential. Three questions can help to shed
      light on this structure: 1) What is the relation of the surrogate endpoint to
      recurrence or death? 2) What is the relation of the intervention (or exposure) to
      the surrogate? 3) To what extent does the surrogate endpoint mediate the relation
      between intervention (exposure) and recurrence or death? To address these
      questions, it is imperative to integrate biomarker studies into ongoing
      pharmacotherapeutic and lifestyle intervention studies with recurrence or
      mortality as explicit endpoints.

PMID- 17182836
TI  - The biological revolution: understanding the impact of SNPs on diet-cancer
      interrelationships.
AB  - Evidence is accumulating that individual risk of neoplasia depends on complex
      interactions among genetic inheritance, a range of exposures both in utero and in
      postnatal life, and the play of chance. Knowledge of the portfolio of genetic
      variants that confer susceptibility or resistance to cancer is limited, and there
      is potential for genome-wide scans and hypothesis-driven studies to reveal novel
      polymorphisms and haplotypes that modify risk. There is only fragmentary evidence
      of the scale and nature of diet-gene interactions that modulate risk of
      neoplasia, but it seems probable that such interactions will play a significant
      role as they do in other complex diseases including cardiovascular disease and
      type 2 diabetes. All existing evidence about diet-gene interactions and cancer
      risk comes from observational studies, and it will be necessary to undertake
      intervention studies to test the hypotheses generated by epidemiologic
      investigations. Because it is very unlikely that primary cancer will be an
      endpoint in dietary intervention studies in the foreseeable future, development
      of robust surrogate endpoints is a high priority. Emerging biological science
      using epigenomics, proteomics, and other molecular technologies appears to offer
      novel approaches to the discovery and validation of surrogate endpoints.

PMID- 17182837
TI  - Metabolomics of a superorganism.
AB  - The human can be thought of as a human-microbe hybrid, and the health of this
      superorganism will be affected by intrinsic properties such as human genetics,
      diurnal cycles, and age and by extrinsic factors such as lifestyle choices (food
      and drink, drug intake) and the acquisition of a stable "healthy" gut microflora
      (the so-called microbiome). Alterations in this superorganism will be manifest in
      the metabolite complement within its serum and urine samples. The unraveling of
      this metabolic compartmentalization in this complex ecosystem will certainly be a
      challenge for systems biology and necessary for defining human health at the
      molecular level. Within the systems biology framework, functional analyses at the
      level of gene expression (transcriptomics), protein translation (proteomics),
      and, more recently, the metabolite network (metabolomics) have become
      increasingly popular. Metabolomics experiments aim to quantify all metabolites in
      a cellular system (cell or tissue) under defined states and at different time
      points so that the dynamics of any biotic, abiotic, or genetic perturbation can
      be accurately assessed. This article provides an overview of metabolomics and
      discusses how data are generated and analyzed within a systems biology framework.
      The role of metabolomics in nutrigenomics is also discussed, as are the concepts
      of the human being a superorganism and the complexities required to be overcome
      to understand human health and disease.

PMID- 17182838
TI  - Frontiers in polyphenols and cancer prevention.

PMID- 17182839
TI  - Using genetic variation to optimize nutritional preemption.
AB  - One of the promises of nutritional genomics is a set of dietary recommendations
      that leverage our understanding of nutrient-gene interaction in the preemptive
      dietary management of complex chronic diseases. Whether nutritional genomics can
      deliver on this promise is a matter of debate and controversy. Although
      nutritional genomics is often viewed as an extension of pharmacogenomics, the
      pharmacogenomics paradigm is a disease-centric reductionistic model that
      overshadows both the complexities and opportunities to be leveraged in preemptive
      nutritional pharmacology. Moreover, the pharmacogenomics model tends to set
      clinical expectations that nutritional genomics may not be able to achieve. The
      biological boundaries of nutritional pharmacology are being tested in many areas
      of preventive medicine such as cardiovascular disease and cancer. In this regard,
      the lessons learned in one disease may be germane to the other. Recent results
      from the Vitamin Intervention for Stroke Prevention (VISP), the Norwegian Vitamin
      (NORVIT), and the Heart Outcomes Prevention Evaluation (HOPE) 2 trials underscore
      the incertitude of translating epidemiologic data into preemptive nutritional
      guidance. Moving ahead, the genetic determinism of the nutrigenomic model needs
      to take on a more holistic and phenotypic focus. To the extent this can be done,
      preemptive nutrition may one day become a safe and practical reality.

PMID- 17182842
TI  - BLOC-1 is required for cargo-specific sorting from vacuolar early endosomes
      toward lysosome-related organelles.
AB  - Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by defects in
      the formation and function of lysosome-related organelles such as melanosomes.
      HPS in humans or mice is caused by mutations in any of 15 genes, five of which
      encode subunits of biogenesis of lysosome-related organelles complex (BLOC)-1, a
      protein complex with no known function. Here, we show that BLOC-1 functions in
      selective cargo exit from early endosomes toward melanosomes. BLOC-1-deficient
      melanocytes accumulate the melanosomal protein tyrosinase-related protein-1
      (Tyrp1), but not other melanosomal proteins, in endosomal vacuoles and the cell
      surface due to failed biosynthetic transit from early endosomes to melanosomes
      and consequent increased endocytic flux. The defects are corrected by restoration
      of the missing BLOC-1 subunit. Melanocytes from HPS model mice lacking a
      different protein complex, BLOC-2, accumulate Tyrp1 in distinct downstream
      endosomal intermediates, suggesting that BLOC-1 and BLOC-2 act sequentially in
      the same pathway. By contrast, intracellular Tyrp1 is correctly targeted to
      melanosomes in melanocytes lacking another HPS-associated protein complex,
      adaptor protein (AP)-3. The results indicate that melanosome maturation requires
      at least two cargo transport pathways directly from early endosomes to
      melanosomes, one pathway mediated by AP-3 and one pathway mediated by BLOC-1 and
      BLOC-2, that are deficient in several forms of HPS.

PMID- 17182843
TI  - Exophilin4/Slp2-a targets glucagon granules to the plasma membrane through unique
      Ca2+-inhibitory phospholipid-binding activity of the C2A domain.
AB  - Rab27a and Rab27b have recently been recognized to play versatile roles in
      regulating the exocytosis of secretory granules and lysosome-related organelles
      by using multiple effector proteins. However, the precise roles of these effector
      proteins in particular cell types largely remain uncharacterized, except for
      those in pancreatic beta cells and in melanocytes. Here, we showed that one of
      the Rab27a/b effectors, exophilin4/Slp2-a, is specifically expressed in
      pancreatic alpha cells, in contrast to another effector, granuphilin, in beta
      cells. Like granuphilin toward insulin granules, exophilin4 promotes the
      targeting of glucagon granules to the plasma membrane. Although the interaction
      of granuphilin with syntaxin-1a is critical for the targeting activity,
      exophilin4 does this primarily through the affinity of its C2A domain toward the
      plasma membrane phospholipids phosphatidylserine and phosphatidylinositol-4,5
      bisphosphate. Notably, the binding activity to phosphatidylserine is inhibited by
      a physiological range of the Ca(2+) concentration attained after secretagogue
      stimulation, which presents a striking contrast to the Ca(2+)-stimulatory
      activity of the C2A domain of synaptotagmin I. Analyses of the mutant suggested
      that this novel Ca(2+)-inhibitory phospholipid-binding activity not only mediates
      docking but also modulates the subsequent fusion of the secretory granules.

PMID- 17182844
TI  - Np95 is implicated in pericentromeric heterochromatin replication and in major
      satellite silencing.
AB  - Heterochromatin plays an important role in transcriptional repression, for the
      correct segregation of chromosomes and in the maintenance of genome stability.
      Pericentric heterochromatin (PH) replication and formation have been proposed to
      occur in the pericentric heterochromatin duplication body (pHDB). A central
      question is how the underacetylated state of heterochromatic histone H4 tail is
      established and controlled, because it is a key event during PH replication and
      is essential to maintain the compacted and silenced state of these regions. Np95
      is a cell cycle regulated and is a nuclear histone-binding protein that also
      recruits HDAC-1 to target promoters. It is essential for S phase and for
      embryonic formation and is implicated in chromosome stability. Here we show that
      Np95 is part of the pHDB, and its functional ablation causes a strong reduction
      in PH replication. Depletion of Np95 also causes a hyperacetylation of lysines 8,
      12, and 16 of heterochromatin histone H4 and an increase of pericentromeric major
      satellite transcription, whose RNAs are key players for heterochromatin
      formation. We propose that Np95 is a new relevant protein involved in
      heterochromatin replication and formation.

PMID- 17182845
TI  - Transferrin receptor 2: evidence for ligand-induced stabilization and redirection
      to a recycling pathway.
AB  - Transferrin receptor 2 (TfR2) is a homologue of transferrin receptor 1 (TfR1),
      the protein that delivers iron to cells through receptor-mediated endocytosis of
      diferric transferrin (Fe(2)Tf). TfR2 also binds Fe(2)Tf, but it seems to function
      primarily in the regulation of systemic iron homeostasis. In contrast to TfR1,
      the trafficking of TfR2 within the cell has not been extensively characterized.
      Previously, we showed that Fe(2)Tf increases TfR2 stability, suggesting that
      trafficking of TfR2 may be regulated by interaction with its ligand. In the
      present study, therefore, we sought to identify the mode of TfR2 degradation, to
      characterize TfR2 trafficking, and to determine how Fe(2)Tf stabilizes TfR2.
      Stabilization of TfR2 by bafilomycin implies that TfR2 traffics to the lysosome
      for degradation. Confocal microscopy reveals that treatment of cells with Fe(2)Tf
      increases the fraction of TfR2 localizing to recycling endosomes and decreases
      the fraction of TfR2 localizing to late endosomes. Mutational analysis of TfR2
      shows that the mutation G679A, which blocks TfR2 binding to Fe(2)Tf, increases
      the rate of receptor turnover and prevents stabilization by Fe(2)Tf, indicating a
      direct role of Fe(2)Tf in TfR2 stabilization. The mutation Y23A in the
      cytoplasmic domain of TfR2 inhibits its internalization and degradation,
      implicating YQRV as an endocytic motif.

PMID- 17182846
TI  - Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent
      growth.
AB  - The cell fate determination factor DACH1 plays a key role in cellular
      differentiation in metazoans. DACH1 is engaged in multiple context-dependent
      complexes that activate or repress transcription. DACH1 can be recruited to DNA
      via the Six1/Eya bipartite transcription (DNA binding/coactivator) complex. c-Jun
      is a critical component of the activator protein (AP)-1 transcription factor
      complex and can promote contact-independent growth. Herein, DACH1 inhibited c-Jun
      induced DNA synthesis and cellular proliferation. Excision of c-Jun with Cre
      recombinase, in c-jun(f1/f1) 3T3 cells, abrogated DACH1-mediated inhibition of
      DNA synthesis. c-Jun expression rescued DACH1-mediated inhibition of cellular
      proliferation. DACH1 inhibited induction of c-Jun by physiological stimuli and
      repressed c-jun target genes (cyclin A, beta-PAK, and stathmin). DACH1 bound c
      Jun and inhibited AP-1 transcriptional activity. c-jun and c-fos were
      transcriptionally repressed by DACH1, requiring the conserved N-terminal (dac and
      ski/sno [DS]) domain. c-fos transcriptional repression by DACH1 requires the SRF
      site of the c-fos promoter. DACH1 inhibited c-Jun transactivation through the
      delta domain of c-Jun. DACH1 coprecipitated the histone deacetylase proteins
      (HDAC1, HDAC2, and NCoR), providing a mechanism by which DACH1 represses c-Jun
      activity through the conserved delta domain. An oncogenic v-Jun deleted of the
      delta domain was resistant to DACH1 repression. Collectively, these studies
      demonstrate a novel mechanism by which DACH1 blocks c-Jun-mediated contact
      independent growth through repressing the c-Jun delta domain.

PMID- 17182847
TI  - The unique-5 and -6 motifs of ZO-1 regulate tight junction strand localization
      and scaffolding properties.
AB  - The proper cellular location and sealing of tight junctions is assumed to depend
      on scaffolding properties of ZO-1, a member of the MAGUK protein family. ZO-1
      contains a conserved SH3-GUK module that is separated by a variable region
      (unique-5), which in other MAGUKs has proven regulatory functions. To identify
      motifs in ZO-1 critical for its putative scaffolding functions, we focused on the
      SH3-GUK module including unique-5 (U5) and unique-6 (U6), a motif immediately C
      terminal of the GUK domain. In vitro binding studies reveal U5 is sufficient for
      occludin binding; U6 reduces the affinity of this binding. In cultured cells, U5
      is required for targeting ZO-1 to tight junctions and removal of U6 results in
      ectopically displaced junction strands containing the modified ZO-1, occludin,
      and claudin on the lateral cell membrane. These results provide evidence that ZO
      1 can control the location of tight junction transmembrane proteins and reveals
      complex protein binding and targeting signals within its SH3-U5-GUK-U6 region. We
      review these findings in the context of regulated scaffolding functions of other
      MAGUK proteins.

PMID- 17182848
TI  - Trypanosoma brucei ARF1 plays a central role in endocytosis and golgi-lysosome
      trafficking.
AB  - The ADP ribosylation factor (Arf)1 orthologue in the divergent eukaryote
      Trypanosoma brucei (Tb) shares characteristics with both Arf1 and Arf6 and has a
      vital role in intracellular protein trafficking. TbARF1 is Golgi localized in
      trypanosomes but associates with the plasma membrane when expressed in human
      cells. Depletion of TbARF1 by RNA interference causes a major decrease in
      endocytosis, which correlates with Rab5 dissociation from early endosomes.
      Although the Golgi remains intact, parasites display enlarged flagellar pockets
      and intracellular flagella. An increase in active GTP-bound TbARF1 in bloodstream
      parasites is rapidly lethal, correlating with a defect in Golgi-to-lysosome
      transport. We conclude that the essential Golgi-localizing T. brucei ARF1 has a
      primary role in the maintenance of both post-Golgi transport and endocytosis and
      that it is significantly divergent from other characterized ARFs.

PMID- 17182849
TI  - Characterization of multiple multivesicular body sorting determinants within
      Sna3: a role for the ubiquitin ligase Rsp5.
AB  - A subset of proteins that transit the endosomal system are directed into the
      intralumenal vesicles of multivesicular bodies (MVBs). MVB formation is critical
      for a variety of cellular functions including receptor down-regulation, viral
      budding, antigen presentation, and the generation of lysosome-related organelles.
      Entry of transmembrane proteins into the intralumenal vesicles of a MVB is a
      highly regulated process that is positively modulated by covalent modification of
      cargoes with ubiquitin. To identify additional MVB sorting signals, we examined
      the previously described ubiquitination-independent MVB cargo Sna3. Although Sna3
      ubiquitination is not essential, Sna3 MVB sorting is positively modulated by its
      ubiquitination. Examination of MVB sorting determinants within a form of Sna3
      lacking all lysine residues identified two critical regions: an amino-terminal
      tyrosine-containing region and a carboxyl-terminal PPAY motif. This PPAY motif
      interacts with the WW domains of the ubiquitin ligase Rsp5, and mutations in
      either the WW or, surprisingly, the HECT domains of Rsp5 negatively impacted MVB
      targeting of lysine-minus Sna3. These data indicate that Rsp5 function is
      required for MVB targeting of Sna3 in a capacity beyond cargo ubiquitination.
      These results uncover a series of determinants impacting Sna3 MVB sorting,
      including unexpected roles for Rsp5.

PMID- 17182850
TI  - Direct binding to Rsp5 mediates ubiquitin-independent sorting of Sna3 via the
      multivesicular body pathway.
AB  - The sorting of most integral membrane proteins into the lumenal vesicles of
      multivesicular bodies (MVBs) is dependent on the attachment of ubiquitin (Ub) to
      their cytosolic domains. However, Ub is not required for sorting of Sna3, an MVB
      vesicle cargo protein in yeast. We show that Sna3 circumvents Ub-mediated
      recognition by interacting directly with Rsp5, an E3 Ub ligase that catalyzes
      monoubiquitination of MVB vesicle cargoes. The PPAY motif in the C-terminal
      cytosolic domain of Sna3 binds the WW domains in Rsp5, and Sna3 is
      polyubiquitinated as a consequence of this association. However, Ub does not
      appear to be required for transport of Sna3 via the MVB pathway because its
      sorting occurs under conditions in which its ubiquitination is impaired.
      Consistent with Ub-independent function of the MVB pathway, we show by electron
      microscopy that the formation of MVB vesicles does not require Rsp5 E3 ligase
      activity. However, cells expressing a catalytically disabled form of Rsp5 have a
      greater frequency of smaller MVB vesicles compared with the relatively broad
      distribution of vesicles seen in MVBs of wild-type cells, suggesting that the
      formation of MVB vesicles is influenced by Rsp5-mediated ubiquitination.

PMID- 17182851
TI  - PALS1 regulates E-cadherin trafficking in mammalian epithelial cells.
AB  - Protein Associated with Lin Seven 1 (PALS1) is an evolutionarily conserved
      scaffold protein that targets to the tight junction in mammalian epithelia. Prior
      work in our laboratory demonstrated that the knockdown of PALS1 in Madin Darby
      canine kidney cells leads to tight junction and polarity defects. We have created
      new PALS1 stable knockdown cell lines with more profound reduction of PALS1
      expression, and a more severe defect in tight junction formation was observed.
      Unexpectedly, we also observed a severe adherens junction defect, and both
      defects were corrected when PALS1 wild type and certain PALS1 mutants were
      expressed in the knockdown cells. We found that the adherens junction structural
      component E-cadherin was not effectively delivered to the cell surface in the
      PALS1 knockdown cells, and E-cadherin puncta accumulated in the cell periphery.
      The exocyst complex was also found to be mislocalized in PALS1 knockdown cells,
      potentially explaining why E-cadherin trafficking is disrupted. Our results
      suggest a broad and evolutionarily conserved role for the tight junction protein
      PALS1 in the biogenesis of adherens junction.

PMID- 17182852
TI  - Mad2-independent spindle assembly checkpoint activation and controlled metaphase
      anaphase transition in Drosophila S2 cells.
AB  - The spindle assembly checkpoint is essential to maintain genomic stability during
      cell division. We analyzed the role of the putative Drosophila Mad2 homologue in
      the spindle assembly checkpoint and mitotic progression. Depletion of Mad2 by
      RNAi from S2 cells shows that it is essential to prevent mitotic exit after
      spindle damage, demonstrating its conserved role. Mad2-depleted cells also show
      accelerated transit through prometaphase and premature sister chromatid
      separation, fail to form metaphases, and exit mitosis soon after nuclear envelope
      breakdown with extensive chromatin bridges that result in severe aneuploidy.
      Interestingly, preventing Mad2-depleted cells from exiting mitosis by a
      checkpoint-independent arrest allows congression of normally condensed
      chromosomes. More importantly, a transient mitotic arrest is sufficient for Mad2
      depleted cells to exit mitosis with normal patterns of chromosome segregation,
      suggesting that all the associated phenotypes result from a highly accelerated
      exit from mitosis. Surprisingly, if Mad2-depleted cells are blocked transiently
      in mitosis and then released into a media containing a microtubule poison, they
      arrest with high levels of kinetochore-associated BubR1, properly localized
      cohesin complex and fail to exit mitosis revealing normal spindle assembly
      checkpoint activity. This behavior is specific for Mad2 because BubR1-depleted
      cells fail to arrest in mitosis under these experimental conditions. Taken
      together our results strongly suggest that Mad2 is exclusively required to delay
      progression through early stages of prometaphase so that cells have time to fully
      engage the spindle assembly checkpoint, allowing a controlled metaphase-anaphase
      transition and normal patterns of chromosome segregation.

PMID- 17182853
TI  - N-WASP involvement in dorsal ruffle formation in mouse embryonic fibroblasts.
AB  - The Wiskott-Aldrich syndrome protein (WASP) family activates the Arp2/3 complex
      leading to the formation of new actin filaments. Here, we study the involvement
      of Scar1, Scar2, N-WASP, and Arp2/3 complex in dorsal ruffle formation in mouse
      embryonic fibroblasts (MEFs). Using platelet-derived growth factor to stimulate
      circular dorsal ruffle assembly in primary E13 and immortalized E9 Scar1(+/+) and
      Scar1 null MEFs, we establish that Scar1 loss does not impair the formation of
      dorsal ruffles. Reduction of Scar2 protein levels via small interfering RNA
      (siRNA) also did not affect dorsal ruffle production. In contrast, wiskostatin, a
      chemical inhibitor of N-WASP, potently suppressed dorsal ruffle formation in a
      dose-dependent manner. Furthermore, N-WASP and Arp2 siRNA treatment significantly
      decreased the formation of dorsal ruffles in MEFs. In addition, the expression of
      an N-WASP truncation mutant that cannot bind Arp2/3 complex blocked the formation
      of these structures. Finally, N-WASP(-/-) fibroblast-like cells generated
      aberrant dorsal ruffles. These ruffles were highly unstable, severely depleted of
      Arp2/3 complex, and diminished in size. We hypothesize that N-WASP and Arp2/3
      complex are part of a multiprotein assembly important for the generation of
      dorsal ruffles and that Scar1 and Scar2 are dispensable for this process.

PMID- 17182854
TI  - Mitogen-activated protein kinase kinase 1-dependent Golgi unlinking occurs in G2
      phase and promotes the G2/M cell cycle transition.
AB  - Two controversies have emerged regarding the signaling pathways that regulate
      Golgi disassembly at the G(2)/M cell cycle transition. The first controversy
      concerns the role of mitogen-activated protein kinase activator mitogen-activated
      protein kinase kinase (MEK)1, and the second controversy concerns the
      participation of Golgi structure in a novel cell cycle "checkpoint." A potential
      simultaneous resolution is suggested by the hypothesis that MEK1 triggers Golgi
      unlinking in late G(2) to control G(2)/M kinetics. Here, we show that inhibition
      of MEK1 by RNA interference or by using the MEK1/2-specific inhibitor U0126
      delayed the passage of synchronized HeLa cells into M phase. The MEK1 requirement
      for normal mitotic entry was abrogated if Golgi proteins were dispersed before M
      phase by treatment of cells with brefeldin A or if GRASP65, which links Golgi
      stacks into a ribbon network, was depleted. Imaging revealed that unlinking of
      the Golgi apparatus begins before M phase, is independent of cyclin-dependent
      kinase 1 activation, and requires MEK signaling. Furthermore, expression of the
      GRASP family member GRASP55 after alanine substitution of its MEK1-dependent
      mitotic phosphorylation sites inhibited both late G(2) Golgi unlinking and the
      G(2)/M transition. Thus, MEK1 plays an in vivo role in Golgi reorganization,
      which regulates cell cycle progression.

PMID- 17182855
TI  - The karyopherin Kap95 regulates nuclear pore complex assembly into intact nuclear
      envelopes in vivo.
AB  - Nuclear pore complex (NPC) assembly in interphase cells requires that new NPCs
      insert into an intact nuclear envelope (NE). Our previous work identified the Ran
      GTPase as an essential component in this process. We proposed that Ran is
      required for targeting assembly factors to the cytoplasmic NE face via a novel,
      vesicular intermediate. Although the molecular target was not identified, Ran is
      known to function by modulating protein interactions for karyopherin (Kap) beta
      family members. Here we characterize loss-of-function Saccharomyces cerevisiae
      mutants in KAP95 with blocks in NPC assembly. Similar to defects in Ran cycle
      mutants, nuclear pore proteins are no longer localized properly to the NE in
      kap95 mutants. Also like Ran cycle mutants, the kap95-E126K mutant displayed
      enhanced lethality with nic96 and nup170 mutants. Thus, Kap95 and Ran are likely
      functioning at the same stage in assembly. However, although Ran cycle mutants
      accumulate small cytoplasmic vesicles, cells depleted of Kap95 accumulated long
      stretches of cytoplasmic membranes and had highly distorted NEs. We conclude that
      Kap95 serves as a key regulator of NPC assembly into intact NEs. Furthermore,
      both Kap95 and Ran may provide spatial cues necessary for targeting of vesicular
      intermediates in de novo NPC assembly.

PMID- 17182856
TI  - Small heat-shock proteins select deltaF508-CFTR for endoplasmic reticulum
      associated degradation.
AB  - Secreted proteins that fail to achieve their native conformations, such as cystic
      fibrosis transmembrane conductance regulator (CFTR) and particularly the
      DeltaF508-CFTR variant can be selected for endoplasmic reticulum (ER)-associated
      degradation (ERAD) by molecular chaperones. Because the message corresponding to
      HSP26, which encodes a small heat-shock protein (sHsp) in yeast was up-regulated
      in response to CFTR expression, we examined the impact of sHsps on ERAD. First,
      we observed that CFTR was completely stabilized in cells lacking two partially
      redundant sHsps, Hsp26p and Hsp42p. Interestingly, the ERAD of a soluble and a
      related integral membrane protein were unaffected in yeast deleted for the genes
      encoding these sHsps, and CFTR polyubiquitination was also unaltered, suggesting
      that Hsp26p/Hsp42p are not essential for polyubiquitination. Next, we discovered
      that DeltaF508-CFTR degradation was enhanced when a mammalian sHsp, alphaA
      crystallin, was overexpressed in human embryonic kidney 293 cells, but wild-type
      CFTR biogenesis was unchanged. Because alphaA-crystallin interacted
      preferentially with DeltaF508-CFTR and because purified alphaA-crystallin
      suppressed the aggregation of the first nucleotide-binding domain of CFTR, we
      suggest that sHsps maintain the solubility of DeltaF508-CFTR during the ERAD of
      this polypeptide.

PMID- 17182857
TI  - Critical role of DNA checkpoints in mediating genotoxic-stress-induced
      filamentous growth in Candida albicans.
AB  - The polymorphic fungus Candida albicans switches from yeast to filamentous growth
      in response to a range of genotoxic insults, including inhibition of DNA
      synthesis by hydroxyurea (HU) or aphidicolin (AC), depletion of the
      ribonucleotide-reductase subunit Rnr2p, and DNA damage induced by methylmethane
      sulfonate (MMS) or UV light (UV). Deleting RAD53, which encodes a downstream
      effector kinase for both the DNA-replication and DNA-damage checkpoint pathways,
      completely abolished the filamentous growth caused by all the genotoxins tested.
      Deleting RAD9, which encodes a signal transducer of the DNA-damage checkpoint,
      specifically blocked the filamentous growth induced by MMS or UV but not that
      induced by HU or AC. Deleting MRC1, the counterpart of RAD9 in the DNA
      replication checkpoint, impaired DNA synthesis and caused cell elongation even in
      the absence of external genotoxic insults. Together, the results indicate that
      the DNA-replication/damage checkpoints are critically required for the induction
      of filamentous growth by genotoxic stress. In addition, either of two mutations
      in the FHA1 domain of Rad53p, G65A, and N104A, nearly completely blocked the
      filamentous-growth response but had no significant deleterious effect on cell
      cycle arrest. These results suggest that the FHA domain, known for its ability to
      bind phosphopeptides, has an important role in mediating genotoxic-stress-induced
      filamentous growth and that such growth is a specific, Rad53p-regulated cellular
      response in C. albicans.

PMID- 17182858
TI  - Villin severing activity enhances actin-based motility in vivo.
AB  - Villin, an actin-binding protein associated with the actin bundles that support
      microvilli, bundles, caps, nucleates, and severs actin in a calcium-dependant
      manner in vitro. We hypothesized that the severing activity of villin is
      responsible for its reported role in enhancing cell plasticity and motility. To
      test this hypothesis, we chose a loss of function strategy and introduced
      mutations in villin based on sequence comparison with CapG. By pyrene-actin
      assays, we demonstrate that this mutant has a strongly reduced severing activity,
      whereas nucleation and capping remain unaffected. The bundling activity and the
      morphogenic effects of villin in cells are also preserved in this mutant. We thus
      succeeded in dissociating the severing from the three other activities of villin.
      The contribution of villin severing to actin dynamics is analyzed in vivo through
      the actin-based movement of the intracellular bacteria Shigella flexneri in cells
      expressing villin and its severing variant. The severing mutations abolish the
      gain of velocity induced by villin. To further analyze this effect, we
      reconstituted an in vitro actin-based bead movement in which the usual capping
      protein is replaced by either the wild type or the severing mutant of villin.
      Confirming the in vivo results, villin-severing activity enhances the velocity of
      beads by more than two-fold and reduces the density of actin in the comets. We
      propose a model in which, by severing actin filaments and capping their barbed
      ends, villin increases the concentration of actin monomers available for
      polymerization, a mechanism that might be paralleled in vivo when an enterocyte
      undergoes an epithelio-mesenchymal transition.

PMID- 17182859
TI  - GCP6 binds to intermediate filaments: a novel function of keratins in the
      organization of microtubules in epithelial cells.
AB  - In simple epithelial cells, attachment of microtubule-organizing centers (MTOCs)
      to intermediate filaments (IFs) enables their localization to the apical domain.
      It is released by cyclin-dependent kinase (Cdk)1 phosphorylation. Here, we
      identified a component of the gamma-tubulin ring complex, gamma-tubulin complex
      protein (GCP)6, as a keratin partner in yeast two-hybrid assays. This was
      validated by binding in vitro of both purified full-length HIS-tagged GCP6 and a
      GCP6(1397-1819) fragment to keratins, and pull-down with native IFs. Keratin
      binding was blocked by Cdk1-mediated phosphorylation of GCP6. GCP6 was apical in
      normal enterocytes but diffuse in K8-null cells. GCP6 knockdown with short
      hairpin RNAs (shRNAs) in CACO-2 cells resulted in gamma-tubulin signal scattered
      throughout the cytoplasm, microtubules (MTs) in the perinuclear and basal
      regions, and microtubule-nucleating activity localized deep in the cytoplasm.
      Expression of a small fragment GCP6(1397-1513) that competes binding to keratins
      in vitro displaced gamma-tubulin from the cytoskeleton and resulted in
      depolarization of gamma-tubulin and changes in the distribution of microtubules
      and microtubule nucleation sites. Expression of a full-length S1397D mutant in
      the Cdk1 phosphorylation site delocalized centrosomes. We conclude that GCP6
      participates in the attachment of MTOCs to IFs in epithelial cells and is among
      the factors that determine the peculiar architecture of microtubules in polarized
      epithelia.

PMID- 17182860
TI  - Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling
      complex and regulates EGF receptor degradation.
AB  - Cdc42-associated tyrosine kinase 1 (ACK1) is a specific down-stream effector of
      Cdc42, a Rho family small G-protein. Previous studies have shown that ACK1
      interacts with clathrin heavy chain and is involved in clathrin-coated vesicle
      endocytosis. Here we report that ACK1 interacted with epidermal growth factor
      receptor (EGFR) upon EGF stimulation via a region at carboxy terminus that is
      highly homologous to Gene-33/Mig-6/RALT. The interaction of ACK1 with EGFR was
      dependent on the kinase activity or tyrosine phosphorylation of EGFR.
      Immunofluorescent staining using anti-EGFR and GFP-ACK1 indicates that ACK1 was
      colocalized with EGFR on EEA-1 positive vesicles upon EGF stimulation.
      Suppression of the expression of ACK1 by ACK-RNAi inhibited ligand-induced
      degradation of EGFR upon EGF stimulation, suggesting that ACK1 plays an important
      role in regulation of EGFR degradation in cells. Furthermore, we identified ACK1
      as an ubiquitin-binding protein. Through an ubiquitin-association (Uba) domain at
      the carboxy terminus, ACK1 binds to both poly- and mono-ubiquitin. Overexpression
      of the Uba domain-deletion mutant of ACK1 blocked the ligand-dependent
      degradation of EGFR, suggesting that ACK1 regulates EGFR degradation via its Uba
      domain. Taken together, our studies suggest that ACK1 senses signal of EGF and
      regulates ligand-induced degradation of EGFR.

PMID- 17182861
TI  - Evaluation of new antituberculosis drugs in mouse models.

PMID- 17182862
TI  - HIF and MIF--a nifty way to delay senescence?

PMID- 17182863
TI  - MyoD, modularity, and myogenesis: conservation of regulators and redundancy in C.
      elegans.

PMID- 17182864
TI  - Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling
      pathway.
AB  - Postnatal growth of the heart is primarily achieved through hypertrophy of
      individual myocytes. Cardiac growth observed in athletes represents adaptive or
      physiological hypertrophy, whereas cardiac growth observed in patients with
      hypertension or valvular heart diseases is called maladaptive or pathological
      hypertrophy. These two types of hypertrophy are morphologically, functionally,
      and molecularly distinct from each other. The serine/threonine protein kinase Akt
      is activated by various extracellular stimuli in a phosphatidylinositol-3 kinase
      dependent manner and regulates multiple aspects of cellular functions including
      survival, growth and metabolism. In this review we will discuss the role of the
      Akt signaling pathway in the heart, focusing on the regulation of cardiac growth,
      contractile function, and coronary angiogenesis. How this signaling pathway
      contributes to the development of physiological/pathological hypertrophy and
      heart failure will also be discussed.

PMID- 17182865
TI  - Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial
      reorientation of the monomers facilitated by the N-terminal domain.
AB  - We report experiments that infer a radical reorientation of tyrosine
      phosphorylated parallel STAT1 dimers to an antiparallel form. Such a change in
      structure allows easy access to a phosphatase. With differentially epitope-tagged
      molecules, we show that the two monomers of a dimer remain together during
      dephosphorylation although they most likely undergo spatial reorientation.
      Extensive single amino acid mutagenesis within crystallographically established
      domains, manipulation of amino acids in an unstructured tether that connects the
      N-terminal domain (ND) to the core of the protein, and the demonstration that
      overexpressed ND can facilitate dephosphorylation of a core molecule lacking an
      ND all support this model: When the tyrosine-phosphorylated STAT1 disengages from
      DNA, the ND dimerizes and somehow assists in freeing the reciprocal pY-SH2
      binding between the monomers of the dimer while ND ND dimerization persists. The
      core of the monomers rotate allowing reciprocal association of the coiled:coil
      and DNA-binding domains to present pY at the two ends of an antiparallel dimer
      for ready dephosphorylation.

PMID- 17182866
TI  - DNA methylation regulates long-range gene silencing of an X-linked homeobox gene
      cluster in a lineage-specific manner.
AB  - DNA methylation is a major epigenetic mechanism that has been suggested to
      control developmental gene regulation during embryogenesis, but its regulatory
      mechanisms remain unclear. In this report, we show that CpG islands associated
      with the X-linked homeobox gene cluster Rhox, which is highly expressed in the
      extraembryonic trophectoderm, are differentially methylated in a stage- and
      lineage-specific manner during the post-implantation development of mice.
      Inactivation of both Dnmt3a and Dnmt3b, DNA methyltransferases essential for the
      initiation of de novo DNA methylation, abolished the establishment of DNA
      methylation and the silencing of Rhox cluster genes in the embryo proper. The
      Dnmt3-dependent CpG-island methylation at the Rhox locus extended for a large
      genomic region ( approximately 1 Mb) containing the Rhox cluster and surrounding
      genes. Complementation experiments using embryonic stem (ES) cells deficient in
      the DNA methyltransferases suggested that the CpG-island methylation by Dnmt3a
      and Dnmt3b was restricted within this large genomic region, and did not affect
      the neighboring genes outside it, implicating the existence of region-specific
      boundaries. Our results suggest that DNA methylation plays important roles in
      both long-range gene silencing and lineage-specific silencing in embryogenesis.

PMID- 17182867
TI  - A diverse and evolutionarily fluid set of microRNAs in Arabidopsis thaliana.
AB  - To better understand the diversity of small silencing RNAs expressed in plants,
      we employed high-throughput pyrosequencing to obtain 887,000 reads corresponding
      to Arabidopsis thaliana small RNAs. They represented 340,000 unique sequences, a
      substantially greater diversity than previously obtained in any species. Most of
      the small RNAs had the properties of heterochromatic small interfering RNAs
      (siRNAs) associated with DNA silencing in that they were preferentially 24
      nucleotides long and mapped to intergenic regions. Their density was greatest in
      the proximal and distal pericentromeric regions, with only a slightly
      preferential propensity to match repetitive elements. Also present were 38 newly
      identified microRNAs (miRNAs) and dozens of other plausible candidates. One miRNA
      mapped within an intron of DICER-LIKE 1 (DCL1), suggesting a second homeostatic
      autoregulatory mechanism for DCL1 expression; another defined the phase for
      siRNAs deriving from a newly identified trans-acting siRNA gene (TAS4); and two
      depended on DCL4 rather than DCL1 for their accumulation, indicating a second
      pathway for miRNA biogenesis in plants. More generally, our results revealed the
      existence of a layer of miRNA-based control beyond that found previously that is
      evolutionarily much more fluid, employing many newly emergent and diverse miRNAs,
      each expressed in specialized tissues or at low levels under standard growth
      conditions.

PMID- 17182868
TI  - Mitf regulation of Dia1 controls melanoma proliferation and invasiveness.
AB  - It is widely held that cells with metastatic properties such as invasiveness and
      expression of matrix metalloproteinases arise through the stepwise accumulation
      of genetic lesions arising from genetic instability and "clonal evolution." By
      contrast, we show here that in melanomas invasiveness can be regulated
      epigenetically by the microphthalmia-associated transcription factor, Mitf, via
      regulation of the DIAPH1 gene encoding the diaphanous-related formin Dia1 that
      promotes actin polymerization and coordinates the actin cytoskeleton and
      microtubule networks at the cell periphery. Low Mitf levels lead to down
      regulation of Dia1, reorganization of the actin cytoskeleton, and increased ROCK
      dependent invasiveness, whereas increased Mitf expression leads to decreased
      invasiveness. Significantly the regulation of Dia1 by Mitf also controls
      p27(Kip1)-degradation such that reduced Mitf levels lead to a p27(Kip1)-dependent
      G1 arrest. Thus Mitf, via regulation of Dia1, can both inhibit invasiveness and
      promote proliferation. The results imply variations in the repertoire of
      environmental cues that determine Mitf activity will dictate the differentiation,
      proliferative, and invasive/migratory potential of melanoma cells through a
      dynamic epigenetic mechanism.

PMID- 17182869
TI  - Muscle cachexia is regulated by a p53-PW1/Peg3-dependent pathway.
AB  - Muscle wasting (cachexia) is an incurable complication associated with chronic
      infection and cancers that leads to an overall poor prognosis for recovery. Tumor
      necrosis factor-alpha (TNFalpha) is a key inflammatory cytokine associated with
      cachexia. TNFalpha inhibits myogenic differentiation and skeletal muscle
      regeneration through downstream effectors of the p53 cell death pathway including
      PW1/Peg3, bax, and caspases. We report that p53 is required for the TNFalpha
      mediated inhibition of myogenesis in vitro and contributes to muscle wasting in
      response to tumor load in vivo. We further demonstrate that PW1 and p53
      participate in a positive feedback regulatory loop in vitro. Consistent with this
      observation, we find that the number of PW1-expressing stem cells in skeletal
      muscle declines significantly in p53 nullizygous mice. Furthermore, gene transfer
      of a dominant-negative form of PW1 into muscle tissue in vivo blocks myofiber
      atrophy in response to tumor load. Taken together, these results show a novel
      role for p53 in mediating muscle stem cell behavior and muscle atrophy, and point
      to new targets for the therapeutic treatment of muscle wasting.

PMID- 17182870
TI  - Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila
      neuroblasts.
AB  - The choice of self-renewal versus differentiation is a fundamental issue in stem
      cell and cancer biology. Neural progenitors of the Drosophila post-embryonic
      brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like
      fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which
      divides terminally to produce two differentiating neuronal/glial daughters. Here
      we show that Aurora-A (AurA) acts as a tumor suppressor by suppressing NB self
      renewal and promoting neuronal differentiation. In aurA loss-of-function mutants,
      supernumerary NBs are produced at the expense of neurons. AurA suppresses tumor
      formation by asymmetrically localizing atypical protein kinase C (aPKC), an NB
      proliferation factor. Numb, which also acts as a tumor suppressor in larval
      brains, is a major downstream target of AurA and aPKC. Notch activity is up
      regulated in aurA and numb larval brains, and Notch signaling is necessary and
      sufficient to promote NB self-renewal and suppress differentiation in larval
      brains. Our data suggest that AurA, aPKC, Numb, and Notch function in a pathway
      that involved a series of negative genetic interactions. We have identified a
      novel mechanism for controlling the balance between self-renewal and neuronal
      differentiation during the asymmetric division of Drosophila larval NBs.

PMID- 17182871
TI  - Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating
      aPKC/Numb cortical polarity and spindle orientation.
AB  - Regulation of stem cell self-renewal versus differentiation is critical for
      embryonic development and adult tissue homeostasis. Drosophila larval neuroblasts
      divide asymmetrically to self-renew, and are a model system for studying stem
      cell self-renewal. Here we identify three mutations showing increased brain
      neuroblast numbers that map to the aurora-A gene, which encodes a conserved
      kinase implicated in human cancer. Clonal analysis and time-lapse imaging in
      aurora-A mutants show single neuroblasts generate multiple neuroblasts (ectopic
      self-renewal). This phenotype is due to two independent neuroblast defects:
      abnormal atypical protein kinase C (aPKC)/Numb cortical polarity and failure to
      align the mitotic spindle with the cortical polarity axis. numb mutant clones
      have ectopic neuroblasts, and Numb overexpression partially suppresses aurora-A
      neuroblast overgrowth (but not spindle misalignment). Conversely, mutations that
      disrupt spindle alignment but not cortical polarity have increased neuroblasts.
      We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self
      renewal and that spindle orientation regulates neuroblast self-renewal.

PMID- 17182872
TI  - The establishment of neuronal properties is controlled by Sox4 and Sox11.
AB  - The progression of neurogenesis relies on proneural basic helix-loop-helix (bHLH)
      transcription factors. These factors operate in undifferentiated neural stem
      cells and induce cell cycle exit and the initiation of a neurogenic program.
      However, the transient expression of proneural bHLH proteins in neural
      progenitors indicates that expression of neuronal traits must rely on previously
      unexplored mechanisms operating downstream from proneural bHLH proteins. Here we
      show that the HMG-box transcription factors Sox4 and Sox11 are of critical
      importance, downstream from proneural bHLH proteins, for the establishment of pan
      neuronal protein expression. Examination of a neuronal gene promoter reveals that
      Sox4 and Sox11 exert their functions as transcriptional activators.
      Interestingly, the capacity of Sox4 and Sox11 to induce the expression of
      neuronal traits is independent of mechanisms regulating the exit of neural
      progenitors from the cell cycle. The transcriptional repressor protein REST/NRSF
      has been demonstrated to block neuronal gene expression in undifferentiated
      neural cells. We now show that REST/NRSF restricts the expression of Sox4 and
      Sox11, explaining how REST/NRSF can prevent precocious expression of neuronal
      proteins. Together, these findings demonstrate a central regulatory role of Sox4
      and Sox11 during neuronal maturation and mechanistically separate cell cycle
      withdrawal from the establishment of neuronal properties.

PMID- 17182873
TI  - Hearing loss and tinnitus prevention initiatives: partnerships for success.

PMID- 17182874
TI  - Analysis of responses to individual items on the tinnitus handicap inventory
      according to severity of tinnitus handicap.
AB  - PURPOSE: To investigate whether certain aspects of tinnitus tend to trouble
      people even when they are not severely affected by tinnitus in many ways. METHOD:
      A total of 274 patients who had requested a tinnitus clinic appointment were
      divided into 4 categories depending on their Tinnitus Handicap Inventory scores:
      no handicap (0-16), mild handicap (18-36), moderate handicap (38-56), or severe
      handicap (58-100). Mean scores for each of the 25 items on the questionnaire were
      calculated and compared within each group and between the 4 groups. RESULTS: Two
      items concerning lack of control over tinnitus and inability to escape it had the
      highest mean score overall and in each category, and elicited positive responses
      from the majority of patients in all but the "no handicap" group. One item
      concerning the belief that tinnitus indicates a terrible disease was found to
      have the lowest mean score overall and in each category and elicited negative
      responses from the majority of patients in all but the "severe handicap" group.
      CONCLUSIONS: These findings indicate that only those who are severely handicapped
      by tinnitus tend to regard it as a terrible disease, and that lack of control and
      inability to escape are common feelings among many people with tinnitus, from the
      most to the least severely handicapped.

PMID- 17182875
TI  - Auditory processing disorder in children diagnosed with nonverbal learning
      disability.
AB  - PURPOSE: To determine whether children with a nonverbal learning disability
      (NVLD) have a higher incidence of auditory processing disorder (APD), especially
      in the tolerance-fading memory type of APD, and what associations could be found
      between performance on neuropsychological, intellectual, memory, and academic
      measures and APD. METHOD: Eighteen children with NVLD ranging in age from 6 to 18
      years received a central auditory processing test battery to determine incidence
      and subtype of APD. Psychological measures for assessment of NVLD included the
      Wechsler Scales, Wide Range Assessment of Memory and Learning, and Wechsler
      Individual Achievement Test. Neuropsychological measures included the Category
      Test, Trails A and B, the Tactual Performance Test, Grooved Pegs, and the Speech
      Sounds Perception Test. Neuropsychological test scores of the NVLD+APD and NVLD
      groups were compared using analysis of covariance procedures, with Verbal IQ and
      Performance IQ as covariates. RESULTS: Sixty-one percent of the children were
      diagnosed with APD, primarily in the tolerance-fading memory subtype. The group
      of children with APD and NVLD had significantly lower scores on Verbal IQ, Digit
      Span, Sentence Memory, Block Design, and Speech Sounds Perception than children
      without APD. An ancillary finding was that the incidence of attention
      deficit/hyperactivity disorder was significantly higher in children with NVLD
      (with and without APD) than in the general population. CONCLUSION: The results
      indicate that children with NVLD are at risk for APD and that there are several
      indicators on neuropsychological assessment suggestive of APD. Collaborative,
      interdisciplinary evaluation of children with learning disorders is needed in
      order to provide effective therapeutic interventions.

PMID- 17182876
TI  - Speech Recognition in noise in children with cochlear implants while listening in
      bilateral, bimodal, and FM-system arrangements.
AB  - PURPOSE: Speech recognition performance in noise was examined in children with
      cochlear implants (CIs) when using (a) a second CI (bilateral group), (b) a
      hearing aid (HA) on the nonimplant ear (bimodal group), and (c) a frequency
      modulation (FM) system on 1 or both sides. METHOD: While always maintaining use
      of the first CI, 2 groups participated in 6 conditions each using various
      listening arrangements with the second CI, HA, or FM system. Speech-in-noise
      thresholds were determined using simple phrases, classroom noise, and a method-of
      limits approach. RESULTS: No group differences were detected across any
      conditions. In the no-FM-system conditions, no significant benefit of bilateral
      or bimodal input was found relative to a single CI. In the FM-system conditions,
      thresholds were significantly lower (up to 20 dB) relative to all other
      conditions when FM-system input was provided to the first-implanted side or to
      both sides simultaneously. CONCLUSIONS: Children's speech-in-noise thresholds did
      not improve when providing input to the second side with a CI or an HA relative
      to a single CI. However, children with CIs had better speech recognition in noise
      with the use of an FM system on one or both sides relative to the conditions with
      no FM system. Binaural conditions with a single FM receiver on the second CI or
      HA yielded significantly poorer performance than any other FM condition.

PMID- 17182877
TI  - Recognition of simulated telephone speech by cochlear implant users.
AB  - PURPOSE: To evaluate cochlear implant users' understanding of telephone speech.
      METHOD: Telephone speech was simulated by band-limiting broadband speech stimuli.
      Multitalker vowel, consonant, and sentence recognition was measured for both
      simulated telephone speech and broadband speech in 10 postlingually deafened
      adult cochlear implant users. The study was approved by the St. Vincent's
      Hospital institutional review board, and signed, informed consent was obtained
      from all participants. RESULTS: There was no significant difference in vowel
      recognition scores between broadband and telephone speech. However, mean
      consonant and sentence recognition scores were significantly poorer with
      telephone speech. CONCLUSIONS: The limited telephone bandwidth significantly
      reduced cochlear implant users' understanding of telephone speech. The effect of
      band-limited speech was highly variable, suggesting that the contribution of high
      frequency information to speech recognition varied significantly among the
      cochlear implant users.

PMID- 17182878
TI  - An adaptive clinical test of temporal resolution.
AB  - PURPOSE: It has been recommended that diagnostic and screening test batteries for
      auditory processing disorder (APD) include a measure of temporal gap detection
      using broadband noise stimuli. Although psychophysical laboratory procedures
      exist for the measurement of temporal resolution, none are clinically feasible.
      This study was designed to obtain preliminary data on a new clinical measure of
      gap detection, the Adaptive Test of Temporal Resolution (ATTR). METHOD: The ATTR,
      a currently available clinical test (Random Gap Detection Test), and a standard
      psychophysical laboratory procedure were used to measure gap detection thresholds
      (GDTs) from a group of 30 young adults with normal hearing. RESULTS: Mean ATTR
      GDTs were 2.2 ms, consistent with GDTs measured using the psychophysical
      laboratory procedure (3.2 ms) and significantly smaller than those measured using
      the Random Gap Detection Test (7.0 ms). CONCLUSIONS: Because it incorporates
      standard adaptive psychophysical methodology in a computer application that can
      be used on any desktop computer but does not depend on specialized hardware for
      application, the ATTR promises to be a clinically feasible addition to the APD
      test battery.

PMID- 17182879
TI  - Audibility and speech perception of children using wide dynamic range compression
      hearing AIDS.
AB  - PURPOSE: This study examined the relation of audibility for frequency-specific
      sounds and the Speech Intelligibility Index (SII) to speech perception abilities
      of children with sensorineural hearing loss using digital signal-processing
      hearing aids with wide dynamic range compression. METHOD: Twenty-six children age
      5-15 years with pure-tone averages (0.5, 1.0, and 2.0 kHz) from 60-98 dB HL
      participated. Three subgroups were created based on the compression
      characteristics of each hearing aid. Minimum audibility was determined using
      aided thresholds for frequency-modulated tones and the SII calculated at 55 and
      70 dB SPL using the simulated real-ear output of the hearing aid. The Lexical
      Neighborhood Test (LNT; K. I. Kirk, D. B. Pisoni, & M. J. Osberger, 1995) was
      presented at 50 and 70 dB SPL. RESULTS: LNT scores at 70 dB SPL were
      significantly higher than at 50 dB SPL. Average aided thresholds at 0.5, 1.0, and
      2.0 kHz were negatively correlated with LNT scores at 50 dB SPL, and SIIs at 55
      and 70 dB SPL were positively correlated with LNT scores at 50 and 70 dB SPL.
      CONCLUSIONS: Results support using aided thresholds and speech test scores at
      soft to loud levels as part of the amplification fitting process.

PMID- 17182880
TI  - Effects of artifact rejection and bayesian weighting on the auditory brainstem
      response during quiet and active behavioral conditions.
AB  - PURPOSE: To evaluate the effects of 2 noise reduction techniques on the auditory
      brainstem response (ABR). METHOD: ABRs of 20 normal hearing adults were recorded
      during quiet and active behavioral conditions using 2 stimulus intensity levels.
      Wave V amplitudes and residual noise root-mean-square values were measured
      following the offline application of artifact rejection and Bayesian weighting.
      Repeated measures analysis of variance and Bonferroni adjusted pairwise t tests
      were utilized to evaluate significant main effects and interactions between the 2
      noise reduction techniques. RESULTS: ABRs recorded during the quiet behavioral
      condition resulted in minimal differences in wave V amplitude and noise reduction
      improvement, suggesting that the 2 techniques were equally effective under ideal
      recording situations. During the active behavioral condition, however, the
      techniques differed significantly in the ability to preserve the evoked potential
      and reduce noise. Consequently, strict artifact rejection levels resulted in an
      inherent underestimation of wave V amplitudes when compared with the Bayesian
      approach. CONCLUSION: Artifact rejection had a detrimental effect on waveform
      morphology of the ABR. This could lead to difficulty in ABR interpretation when
      patients are active and ultimately result in diagnostic errors.

PMID- 17182881
TI  - Mechanism of injury in uromodulin-associated kidney disease.

PMID- 17182882
TI  - Novel approaches in the investigation of acute kidney injury.

PMID- 17182883
TI  - Immunohistochemical detection of hypoxia-inducible factor-1alpha in human renal
      allograft biopsies.
AB  - Although it generally is accepted that renal hypoxia may occur in various
      situations after renal transplantation, direct evidence for such hypoxia is
      lacking, and possible implications on graft pathophysiology remain obscure.
      Hypoxia-inducible factors (HIF) are regulated at the protein level by oxygen
      dependent enzymes and, hence, allow for tissue hypoxia detection. With the use of
      high-amplification HIF-1alpha immunohistochemistry in renal biopsies, hypoxia is
      shown at specific time points after transplantation with clinicohistologic
      correlations. Immediately after engraftment, in primarily functioning grafts,
      abundant HIF-1alpha is present and correlates with cold ischemic time >15 h
      and/or graft age >50 yr (P < 0.04). In contrast, a low HIF-1alpha score
      correlates with primary nonfunction, likely reflecting loss of oxygen consumption
      for tubular transport. Protocol biopsies at 2 wk show widespread HIF-1alpha
      induction, irrespective of histology. Beyond 3 mo, both protocol biopsies and
      indicated biopsies are virtually void of HIF-1alpha, with the only exception
      being clinical/subclinical rejection. HIF-derived transcriptional adaptation to
      hypoxia may counterbalance, at least partly, the negative impact of cold
      preservation and warm reflow injury. Transient hypoxia at 2 wk may be induced by
      hyperfiltration, hypertrophy, calcineurin inhibitor-induced toxicity, or a
      combination of these. Lack of detectable HIF-1alpha at 3 mo and beyond suggests
      that at this time point, graft oxygen homeostasis occurs. The strong correlation
      between hypoxia and clinical/subclinical rejection in long-term grafts suggests
      that hypoxia is involved in such graft dysfunction, and HIF-1alpha
      immunohistochemistry could enhance the specific diagnosis of acute rejection.

PMID- 17182884
TI  - Retinoic acid inhibits HIV-1-induced podocyte proliferation through the cAMP
      pathway.
AB  - HIV-associated nephropathy is characterized by renal podocyte proliferation and
      dedifferentiation. This study found that all-trans retinoic acid (atRA) reverses
      the effects of HIV-1 infection in podocytes. Treatment with atRA reduced cell
      proliferation rate by causing G1 arrest and restored the expression of the
      differentiation markers (synaptopodin, nephrin, podocin, and WT-1) in HIV-1
      infected podocytes. It is interesting that both atRA and 9-cis RA increased
      intracellular cAMP levels in podocytes. Podocytes expressed most isoforms of
      retinoic acid receptors (RAR) and retinoid X receptors (RXR) with the exception
      of RXRgamma. RARalpha antagonists blocked atRA-induced cAMP production and its
      antiproliferative and prodifferentiation effects on podocytes, suggesting that
      RARalpha is required. For determination of the effect of increased intracellular
      cAMP on HIV-infected podocytes, cells were stimulated with either forskolin or 8
      bromo-cAMP. Both compounds inhibited cell proliferation significantly and
      restored synaptopodin expression in HIV-infected podocytes. The effects of atRA
      were abolished by Rp-cAMP, an inhibitor of the cAMP/protein kinase A pathway and
      were enhanced by rolipram, an inhibitor of phosphodiesterase 4, suggesting that
      the antiproliferative and prodifferentiation effects of atRA on HIV-infected
      podocytes are cAMP dependent. Furthermore, both atRA and forskolin suppressed HIV
      induced mitogen-activated protein kinase 1 and 2 and Stat3 phosphorylation. In
      vivo, atRA reduced proteinuria, cell proliferation, and glomerulosclerosis in HIV
      1-transgenic mice. These findings suggest that atRA reverses the abnormal
      phenotype in HIV-1-infected podocytes by stimulating RARalpha-mediated
      intracellular cAMP production. These results demonstrate the mechanism by which
      atRA reverses the proliferation of podocytes that is induced by HIV-1.

PMID- 17182885
TI  - Oxidized low-density lipoproteins activate CD4+ T cell apoptosis in patients with
      end-stage renal disease through Fas engagement.
AB  - Oxidized LDL (oxLDL) are cytotoxic to vascular cells, but their possible toxic
      action on T cells from patients with ESRD has not been evaluated. oxLDL
      concentrations were measured and compared in patients who were on long-term
      hemodialysis (HD), in patients who had ESRD and were on continuous ambulatory
      peritoneal dialysis, in nondialyzed patients with chronic kidney disease, and in
      age- and gender-matched control subjects. In parallel, the proliferative capacity
      of CD69+/CD4+ T cells and their rate of apoptosis, IL-2 expression, and
      intracellular expression of Bcl-2 and Bax were determined in vitro. The oxLDL
      concentrations were significantly higher in HD patients (all P = 0.001). Upon
      phytohemagglutinin stimulation, CD69+/CD4+ T cells from HD patients proliferated
      significantly less than those from the other patients' group (both P < 0.001).
      oxLDL but not the native LDL were led to CD69+/CD4+ T cells' program cell death
      in a dosage- and time-dependent manner through Fas pathway (P = 0.001). Cell
      surface Fas expression was followed by DNA fragmentation when CD69+/CD4+ T cells
      from HD patients or control subjects were cultured with oxLDL (200 microg/ml; 31
      +/- 3 versus 25 +/- 3%; P = 0.001). In the presence of oxLDL, CD69+/CD4+ T cells
      from HD patients expressed significantly lower IL-2 levels, which strongly
      correlated with a decrease in the antiapoptotic Bcl-2 and conversely with an
      increase in the proapoptotic Bax expression. In conclusion, these data suggest
      that, in HD patients, exposure of activated CD4+ T cells to oxLDL leads to Fas
      mediated apoptosis in association with inhibition of IL-2 expression.
      Subsequently, this may favor activation of mitochondria-dependent apoptotic
      pathways, leading to activated CD4+ T cell dysfunction.

PMID- 17182886
TI  - Reversal of the adynamic bone disorder and decreased vascular calcification in
      chronic kidney disease by sevelamer carbonate therapy.
AB  - A model of chronic kidney disease (CKD)-induced vascular calcification (VC) that
      complicates the metabolic syndrome was produced. In this model, the metabolic
      syndrome is characterized by severe atherosclerotic plaque formation,
      hypertension, type 2 diabetes, obesity, and hypercholesterolemia, and CKD
      stimulates calcification of the neointima and tunica media of the aorta. The CKD
      in this model is associated the adynamic bone disorder form of renal
      osteodystrophy. The VC of the model is associated with hyperphosphatemia, and
      control of the serum phosphorus both in this animal model and in humans has been
      preventive in the development of VC. This article reports studies that
      demonstrate reduction of established VC by the addition of sevelamer carbonate to
      the diets of this murine metabolic syndrome model with CKD. Sevelamer, besides
      normalizing the serum phosphorus, surprisingly, reversed the CKD-induced
      trabecular osteopenia. Sevelamer therapy increased osteoblast surfaces in the
      metaphyseal trabeculae of the tibia and femur. It also increased osteoid surfaces
      and, importantly, bone formation rates. In addition, sevelamer was found to be
      effective in decreasing serum cholesterol levels. These results suggest that
      sevelamer may have important actions in decreasing diabetic and uremic
      vasculopathy and that sevelamer carbonate may be capable of increasing bone
      formation rates that are suppressed by diabetic nephropathy.

PMID- 17182887
TI  - Myocardial function, energy provision, and carnitine deficiency in experimental
      uremia.
AB  - Cardiac complications are the leading cause of mortality in patients with chronic
      renal failure. Secondary carnitine deficiency, which is frequently observed in
      hemodialysis patients, has been associated with cardiac hypertrophy and heart
      failure and may impair myocardial fatty acid oxidation. In chronic kidney
      disease, impaired carnitine homeostasis also may affect myocardial metabolism. In
      this study, myocardial function and substrate oxidation in conjunction with
      carnitine deficiency were investigated in experimental renal failure. Uremia was
      induced in male Sprague-Dawley rats via a two-stage five-sixths nephrectomy.
      Cardiac function and substrate oxidation were assessed in vitro by means of
      isovolumic perfusion using 13C nuclear magnetic resonance at 3 and 6 wk of
      uremia. Renal impairment as assessed by serum creatinine was more severe
      initially and was associated with a significant deficiency in serum free
      carnitine (43%; P < 0.001) and elevated acyl carnitine/free carnitine ratio.
      Myocardial tissue carnitine concentrations, however, were unaffected. A moderate
      degree of cardiac hypertrophy (10 to 14%; P < 0.05) was observed in uremia
      without evidence of dysfunction or changes in myocardial substrate utilization.
      It is concluded that renal dysfunction is associated with cardiac hypertrophy in
      the presence of normal myocardial carnitine levels, despite a significant
      depletion in serum carnitine. This may be a factor in maintaining normal cardiac
      function and metabolism.

PMID- 17182888
TI  - An essential role for constitutive endocytosis, but not activity, in the axonal
      targeting of the CB1 cannabinoid receptor.
AB  - In central neurons, the cell-surface distribution of cannabinoid receptor subtype
      1 (CB(1)) is highly polarized toward axons and is associated with synaptic
      terminals, in which it is well-positioned to modulate neurotransmitter release.
      It has been suggested that high levels of constitutive activity mediate CB(1)
      receptor axonal targeting, leading to domain-specific endocytosis. We have
      investigated further the mechanisms that underlie CB(1) receptor axonal
      polarization in hippocampal neurons and found that constitutive activity is not
      an essential requirement for this process. We demonstrate that the cell-surface
      distribution of an N-terminally tagged, fluorescent CB(1) receptor fusion-protein
      is almost exclusively localized to the axon when expressed in cultured
      hippocampal neurons. Inhibition of endocytosis by cotransfection with a dominant
      negative dynamin-1 (K44A) mutant traps both recombinant and endogenous CB(1)
      receptors at the somatodendritic cell surface. However, this effect could not be
      mimicked by inhibiting constitutive activity or receptor activation, either by
      expressing mutant receptors that lack these properties or by treatment with CB(1)
      receptor antagonists possessing inverse agonist activity. These data are
      consistent with a revised model in which domain-specific endocytosis regulates
      the functional polarization of CB(1) receptors, but this process is distinct from
      constitutive activity.

PMID- 17182889
TI  - Tumor necrosis factor regulation of apoptosis in mouse preimplantation embryos
      and its antagonism by transforming growth factor alpha/phosphatidylionsitol 3
      kinase signaling system.
AB  - Survival and apoptosis of cells in preimplantation embryos are fundamental for
      successful pregnancy. Relevant to these processes, tumor necrosis factor (TNF)
      and transforming growth factor alpha (TGFA) are produced by mammalian oviducts
      and uteri. In early embryos, TNF induces apoptosis, whereas TGFA could act as a
      survival factor. Here we investigated the TNF regulation of apoptosis in early
      mouse embryos and its antagonism by TGFA. TNF receptor superfamily, member 1a
      mRNA was detectable throughout early embryonic stages, with an increase after the
      early blastocyst stage, whereas the expression of TNF receptor superfamily,
      member 1b transcripts were detected only at the expanded blastocyst stage.
      Although pregnant uteri produced TNF, physiologic levels were low during the
      preimplantation period. Treatment with TNF inhibited the development of two-cell
      stage embryos to blastocysts showing decreased proliferation and increased
      apoptosis both in vitro and in vivo. These detrimental effects of TNF on early
      embryo development and survival were blocked by a neutralizing anti-TNF antibody.
      In addition to the death receptor-mediated pathway, TNF-induced apoptosis was
      further mediated by disruption of mitochondrial functions, characterized by
      release of cytochrome c and activation of caspase 9. The proapoptotic effects of
      TNF in blastocysts were counteracted by cotreatment with TGFA. The antagonistic
      effect of TGFA on TNF-induced apoptosis was blocked by phosphatidylionsitol 3
      kinase (PI3K) inhibitors. The present findings demonstrate the stage-selective
      susceptibility to the apoptosis-inducing effect of TNF in mouse preimplantation
      embryos and that the TGFA/PI3K signaling system has an important role in the
      control of TNF-induced apoptosis in blastocysts.

PMID- 17182890
TI  - Topoisomerase II-mediated breaks in spermatozoa cause the specific degradation of
      paternal DNA in fertilized oocytes.
AB  - We have demonstrated that mouse spermatozoa can cleave their DNA into 50-kb
      fragments when treated with Triton X-100, MnCl(2), and CaCl(2). This cleavage,
      which is termed sperm chromatin fragmentation (SCF), is mediated by topoisomerase
      IIB (TOP2B) following stimulation by a factor in the epididymal fluid, most
      likely a nuclease, and can be at least partially religated by EDTA. When the
      protamines are removed, this DNA breakage is followed by digestion of the DNA by
      a nuclease(s). We tested whether the oocyte could repair TOP2B-induced sperm DNA
      breaks and whether partial religation by EDTA would allow spermatozoa to
      fertilize the oocytes normally. Oocytes injected with untreated spermatozoa
      developed normally. However, oocytes injected with spermatozoa treated with
      MnCl(2) and CaCl(2) to induce SCF, with or without subsequent EDTA treatment,
      failed to develop. In both of these treatment groups, the maternal pronuclei
      developed normally and replicated their DNA. However the paternal pronuclei did
      not replicate their DNA and this DNA began to disappear 6 h postinjection, which
      corresponded approximately to the time at which maternal DNA replication was
      initiated. These data suggest that when TOP2B is induced to cleave sperm DNA
      before fertilization, the paternal DNA is subsequently degraded by a highly
      regulated mechanism that does not affect the maternal chromatin. Furthermore,
      partial religation by EDTA of TOP2B-induced breaks prevents neither the
      inhibition of DNA synthesis nor DNA degradation.

PMID- 17182891
TI  - Upregulation of placental indoleamine 2,3-dioxygenase by human chorionic
      gonadotropin.
AB  - We tested the hypothesis that hCG can upregulate human trophoblast indoleamine 2,
      3-dioxygenase (INDO), which catalyzes the breakdown of tryptophan in villous
      circulation. The results revealed that it can. Treatment of human trophoblasts
      with hCG resulted in a time and dose dependent increase in INDO mRNA and protein
      levels and its enzyme activity. The hCG effect was hormone specific and required
      the dimer conformation of hCG. The hCG effect required its receptors and was
      mediated by a cAMP dependent, but protein kinase A independent, mitogen-activated
      protein kinase 3/1 (MAPK3/1) signaling mechanism. In summary, the present data
      demonstrate a novel hCG effect on human placental INDO, which probably plays a
      key role at maternal fetal interface in preventing fetal rejection.

PMID- 17182892
TI  - Proper chromatin condensation and maintenance of histone H3 phosphorylation
      during mouse oocyte meiosis requires protein phosphatase activity.
AB  - We have shown okadaic acid (OA) and calyculin-A (CLA) inhibition of mouse oocyte
      phosphoprotein phosphatase 1 (PPP1C) and/or phosphoprotein phosphatase 2A
      (PPP2CA) results in aberrant chromatin condensation, as evidenced by the
      inability to resolve bivalents. Phosphorylation of histone H3 at specific
      residues is thought to regulate chromatin condensation. Therefore, we examined
      changes in histone H3 phosphorylation during oocyte meiosis and the potential
      regulation by protein PPPs. Western blot and immunocytochemical analysis revealed
      histone H3 phosphorylation changed during mouse oocyte meiosis, with changes in
      chromatin condensation. Germinal vesicle-intact (GV-intact; 0 h) oocytes had no
      phospho-Ser10 but did have phospho-Ser28 histone H3. Oocytes that had undergone
      germinal vesicle breakdown (GVBD; 2 h) and progressed to metaphase I (MI; 7 h)
      and MII (16 h) had phosphorylated Ser10 and Ser28 histone H3 associated with
      condensed chromatin. To determine whether OA-induced aberrations in chromatin
      condensation were due to alterations in levels of histone H3 phosphorylation, we
      assessed phosphorylation of Ser10 and Ser28 residues following PPP inhibition.
      Oocytes treated with OA (1 microM) displayed increased phosphorylation of histone
      H3 at both Ser10 and Ser28 compared with controls. To begin to elucidate which OA
      sensitive PPP is responsible for regulating chromatin condensation and histone H3
      phosphorylation, we examined spatial and temporal localization of OA-sensitive
      PPPs, PPP1C, and PPP2CA. PPPC2A did not localize to condensed chromatin, whereas
      PPP1beta (PPP1CB) associated with condensing chromatin in GVBD, MI, and MII
      oocytes. Additionally, Western blot and immunocytochemistry confirmed presence of
      the PPP1C regulatory inhibitor subunit 2 (PPP1R2) in oocytes at condensed
      chromatin during meiosis and indicated a change in PPP1R2 phosphorylation.
      Inhibition of oocyte glycogen synthase kinase 3 (GSK3) appeared to regulate
      phosphorylation of PPP1R2. Furthermore, inhibition of GSK3 resulted in aberrant
      oocyte bivalent formation similar to that observed following PPP inhibition.
      These data suggest that PPP1CB is the OA/CLA-sensitive PPP that regulates oocyte
      chromatin condensation through regulation of histone H3 phosphorylation.
      Furthermore, GSK3 inhibition results in aberrant chromatin condensation and
      appears to regulate phosphorylation of PPP1R2.

PMID- 17182893
TI  - Bovine sperm hyperactivation is promoted by alkaline-stimulated Ca2+ influx.
AB  - Sperm hyperactivated motility is characterized by high flagellar bend amplitude
      and asymmetrical beating, which are detected by computer-assisted sperm motility
      analysis as increased curvilinear velocity and lateral head movement. It is
      required for sperm penetration of the oocyte zona pellucida during fertilization
      and is induced by an increase in flagellar Ca(2+). Our objective was to determine
      whether pH plays a role in promoting Ca signaling of hyperactivated motility. The
      cell-permeant weak base NH(4)Cl increased curvilinear velocity and amplitude of
      lateral head movement of bovine sperm, indicative of hyperactivation.
      Fluorometric recordings of sperm loaded with BCECF-AM or fluo3-AM, revealed that
      NH(4)Cl evoked elevations of intracellular pH and Ca(2+), respectively, with the
      rise in pH occurring more rapidly than that of Ca(2+). Single-cell image analysis
      showed increased Ca(2+) levels in the flagellum in response to NH(4)Cl. When
      extracellular Ca(2+) was lowered with BAPTA (1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid) prior to treatment with NH(4)Cl, intracellular pH was
      increased, but elevation of Ca(2+) and hyperactivation were diminished. This
      suggests that the rise in intracellular pH precedes an influx of Ca(2+). The
      Ca(2+) channel blocker Ni(2+) also diminished NH(4)Cl stimulation of
      hyperactivation, demonstrating that Ca(2+) entry is required for maximal
      expression of hyperactivation. Ca(2+) ionophore produced an increase in Ca(2+)
      that was 3-fold greater than that produced by NH(4)Cl; however, it produced a
      weaker hyperactivation response. These results indicate that a rise in pH
      increases intracellular Ca(2+)and promotes hyperactivation primarily by
      stimulating Ca(2+) influx, but also by other mechanisms.

PMID- 17182894
TI  - Comparison of Pax1/9 locus reveals 500-Myr-old syntenic block and evolutionary
      conserved noncoding regions.
AB  - Identification of conserved genomic regions within and between different genomes
      is crucial when studying genome evolution. Here, we described regions of strong
      synteny conservation between vertebrate deuterostomes (tetrapods and teleosts)
      and invertebrate deuterostomes (amphioxus and sea urchin). The shared gene
      contents across phylogenetically distant species demonstrate that the
      conservation of the regions stemmed from an ancestral segment instead of a series
      of independent convergent events. Comparison of the syntenic regions allows us to
      postulate the primitive gene organization in the last common ancestor of
      deuterostomes and the evolutionary events that occurred to the 3 distinct
      lineages of sea urchin, amphioxus, and vertebrates after their separation. In
      addition, alignment of the syntenic regions led to the identification of 8
      noncoding evolutionarily conserved regions shared between amphioxus and
      vertebrates. To our knowledge, this is the first report of conserved noncoding
      sequences shared by vertebrates and nonvertebrates. These noncoding sequences
      have high possibility of being elements that regulate neighboring genes. They are
      likely to be a factor in the maintenance of conserved synteny over long
      phylogenetic distance in different deuterostome lineages.

PMID- 17182895
TI  - Multilocus analysis of nucleotide variation and speciation in Oryza officinalis
      and its close relatives.
AB  - Nucleotide variation in 10 unlinked nuclear genes was investigated in species
      wide samples of Oryza officinalis and its close relatives (Oryza eichingeri and
      Oryza rhizomatis). Average estimates of nucleotide diversity were the lowest in
      O. rhizomatis ((sil) = 0.0038) and the highest in O. eichingeri ((sil) = 0.0057)
      that is disjunctly distributed in Africa and Sri Lanka. These wild rice species
      appeared to harbor relatively low levels of nucleotide variation relative to
      other plant species because the diversity level of O. eichingeri is only 23-46%
      of those in Zea species and 35% of that in Arabidopsis thaliana. The lower
      nucleotide diversity in these Oryza species could be best explained by their
      smaller historic effective population sizes. The speciation model test indicated
      that O. officinalis and its close relatives might have undergone a process of
      population contraction since divergence from their ancestor. Incongruent
      topologies among 10 gene trees, particularly regarding the positions of O.
      eichingeri and O. rhizomatis accessions might be attributed to lineage sorting
      arising from ancient polymorphism and hybridization/introgression between the Sri
      Lankan O. eichingeri and O. rhizomatis. However, the null hypothesis of the
      isolation model was not rejected for any contrast between taxa, which suggested
      that no subsequent gene flow shaped the present patterns of nucleotide variation
      since their divergence and that introgression was not pervasive in this group of
      species. Our molecular dating provides an approximate divergence time of 0.37 Myr
      between 2 geographical races of O. eichingeri, much more recent compared with the
      times of other speciation events in this group (0.63-0.68 Myr). A long-distance
      dispersal from West Africa to Sri Lanka was more likely to play a role in the
      disjunct distribution of O. eichingeri.

PMID- 17182896
TI  - Genetic evidence for the convergent evolution of light skin in Europeans and East
      Asians.
AB  - Human skin pigmentation shows a strong positive correlation with ultraviolet
      radiation intensity, suggesting that variation in skin color is, at least
      partially, due to adaptation via natural selection. We investigated the evolution
      of pigmentation variation by testing for the presence of positive directional
      selection in 6 pigmentation genes using an empirical F(ST) approach, through an
      examination of global diversity patterns of these genes in the Centre d'Etude du
      Polymorphisme Humain (CEPH)-Diversity Panel, and by exploring signatures of
      selection in data from the International HapMap project. Additionally, we
      demonstrated a role for MATP in determining normal skin pigmentation variation
      using admixture mapping methods. Taken together (with the results of previous
      admixture mapping studies), these results point to the importance of several
      genes in shaping the pigmentation phenotype and a complex evolutionary history
      involving strong selection. Polymorphisms in 2 genes, ASIP and OCA2, may play a
      shared role in shaping light and dark pigmentation across the globe, whereas
      SLC24A5, MATP, and TYR have a predominant role in the evolution of light skin in
      Europeans but not in East Asians. These findings support a case for the recent
      convergent evolution of a lighter pigmentation phenotype in Europeans and East
      Asians.

PMID- 17182897
TI  - Origin and evolution of the mitochondrial aminoacyl-tRNA synthetases.
AB  - Many theories favor a fusion of 2 prokaryotic genomes for the origin of the
      Eukaryotes, but there are disagreements on the origin, timing, and cellular
      structures of the cells involved. Equally controversial is the source of the
      nuclear genes for mitochondrial proteins, although the alpha-proteobacterial
      contribution to the mitochondrial genome is well established. Phylogenetic
      inferences show that the nuclearly encoded mitochondrial aminoacyl-tRNA
      synthetases (aaRSs) occupy a position in the tree that is not close to any of the
      currently sequenced alpha-proteobacterial genomes, despite cohesive and
      remarkably well-resolved alpha-proteobacterial clades in 12 of the 20 trees. Two
      or more alpha-proteobacterial clusters were observed in 8 cases, indicative of
      differential loss of paralogous genes or horizontal gene transfer. Replacement
      and retargeting events within the nuclear genomes of the Eukaryotes was indicated
      in 10 trees, 4 of which also show split alpha-proteobacterial groups. A majority
      of the mitochondrial aaRSs originate from within the bacterial domain, but none
      specifically from the alpha-Proteobacteria. For some aaRS, the endosymbiotic
      origin may have been erased by ongoing gene replacements on the bacterial as well
      as the eukaryotic side. For others that accurately resolve the alpha
      proteobacterial divergence patterns, the lack of affiliation with mitochondria is
      more surprising. We hypothesize that the ancestral eukaryotic gene pool hosted
      primordial "bacterial-like" genes, to which a limited set of alpha
      proteobacterial genes, mostly coding for components of the respiratory chain
      complexes, were added and selectively maintained.

PMID- 17182898
TI  - Hedgehog signaling.

PMID- 17182899
TI  - Centriole/basal body morphogenesis and migration during ciliogenesis in animal
      cells.
AB  - Cilia, either motile or immotile, exist on most cells in the human body. There
      are several different mechanisms of ciliogenesis, which enable the production of
      many kinds of cilia and flagella: motile and immotile, transient and long-lived.
      These can be linked to the cell cycle or associated with differentiation. A
      primary cilium is extended from a basal body analogous to the mitotic centrioles,
      whereas the several hundred centrioles needed to form the cilia of a multi
      ciliated cell can be generated by centriolar or acentriolar pathways. Little is
      known about the molecular control of these pathways and most of our knowledge
      comes from ultrastructural studies. The increasing number of genetic diseases
      linked to dysfunctional cilia and basal bodies has renewed interest in this area,
      and recent proteomic and cell biological studies in model organisms have helped
      to shed light on the molecular components of these enigmatic organelles.

PMID- 17182900
TI  - Rap1: a key regulator in cell-cell junction formation.
AB  - Rap1 is a Ras-like small GTPase that is activated by many extracellular stimuli
      and strongly implicated in the control of integrin-mediated cell adhesion. Recent
      evidence indicates that Rap1 also plays a key role in formation of cadherin-based
      cell-cell junctions. Indeed, inhibition of Rap1 generates immature adherens
      junctions, whereas activation of Rap1 tightens cell-cell junctions.
      Interestingly, Rap1 guanine nucleotide exchange factors, such as C3G and PDZ-GEF,
      are directly linked to E-cadherin or to other junction proteins. Furthermore,
      several junction proteins, such as afadin/AF6 and proteins controlling the actin
      cytoskeleton, function as effectors of Rap1. These findings point to a role of
      Rap1 in spatial and temporal control of cell-cell junction formation.

PMID- 17182901
TI  - Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells.
AB  - Embryonic stem (ES) cells are self-renewing cells that maintain pluripotency to
      differentiate into all types of cells. Because of their potential to provide a
      variety of tissues for use in regenerative medicine, there is great interest in
      the identification of growth factors that govern these unique properties of ES
      cells. However, the signaling pathways controlling ES cell proliferation remain
      largely unknown. Since transforming growth factor beta (TGFbeta) superfamily
      members have been implicated in the processes of early embryogenesis, we
      investigated their roles in ES cell self-renewal. Inhibition of activin-Nodal
      TGFbeta signaling by Smad7 or SB-431542 dramatically decreased ES cell
      proliferation without decreasing ES pluripotency. By contrast, inhibition of bone
      morphogenetic protein (BMP) signaling by Smad6 did not exhibit such effects,
      suggesting that activin-Nodal-TGFbeta signaling, but not BMP signaling, is
      indispensable for ES cell propagation. In serum-free culture, supplementation of
      recombinant activin or Nodal, but not TGFbeta or BMP, significantly enhanced ES
      cell propagation without affecting pluripotency. We also found that activin-Nodal
      signaling was constitutively activated in an autocrine fashion in serum-free
      cultured ES cells, and that inhibition of such endogenous signaling by SB-431542
      decreased ES cell propagation in serum-free conditions. These findings suggest
      that endogenously activated autocrine loops of activin-Nodal signaling promote ES
      cell self-renewal.

PMID- 17182902
TI  - C-terminal domains deliver the DNA replication factor Ciz1 to the nuclear matrix.
AB  - Cip1-interacting zinc finger protein 1 (Ciz1) stimulates DNA replication in vitro
      and is required for mammalian cells to enter S phase. Here, we show that a
      significant proportion of Ciz1 is retained in nuclear foci following extraction
      with nuclease and high salt. This suggests that Ciz1 is normally immobilized by
      interaction with non-chromatin nuclear structures, consistent with the nuclear
      matrix. Furthermore, matrix-associated Ciz1 foci strikingly colocalize with sites
      of newly synthesized DNA in S phase nuclei, suggesting that Ciz1 is present in
      DNA replication factories. Analysis of green fluorescent protein-tagged fragments
      indicates that nuclear immobilization of Ciz1 is mediated by sequences in its C
      terminal third, encoded within amino acids 708-830. Immobilization occurs in a
      cell-cycle-dependent manner, most probably during late G1 or early S phase, to
      coincide with its reported point of action. Although C-terminal domains are
      sufficient for immobilization, N-terminal domains are also required to specify
      focal organization. Combined with previous work, which showed that the DNA
      replication activity of Ciz1 is encoded by N-terminal sequences, we suggest that
      Ciz1 is composed of two functionally distinct domains: an N-terminal replication
      domain and a C-terminal nuclear matrix anchor. This could contribute to the
      formation or function of DNA replication factories in mammalian cells.

PMID- 17182904
TI  - Role for the lateral olivocochlear neurons in auditory function. Focus on
      "Selective removal of lateral olivocochlear efferents increases vulnerability to
      acute acoustic injury".

PMID- 17182905
TI  - Heschl's gyrus, posterior superior temporal gyrus, and mid-ventrolateral
      prefrontal cortex have different roles in the detection of acoustic changes.
AB  - A part of the auditory system automatically detects changes in the acoustic
      environment. This preattentional process has been studied extensively, yet its
      cerebral origins have not been determined with sufficient accuracy to allow
      comparison to established anatomical and functional parcellations. Here we used
      event-related functional MRI and EEG in a parametric experimental design to
      determine the cortical areas in individual brains that participate in the
      detection of acoustic changes. Our results suggest that automatic change
      processing consists of at least three stages: initial detection in the primary
      auditory cortex, detailed analysis in the posterior superior temporal gyrus and
      planum temporale, and judgment of sufficient novelty for the allocation of
      attentional resources in the mid-ventrolateral prefrontal cortex.

PMID- 17182906
TI  - Singing-related activity of identified HVC neurons in the zebra finch.
AB  - High vocal center (HVC) is part of the premotor pathway necessary for song
      production and is also a primary source of input to the anterior forebrain
      pathway (AFP), a basal ganglia-related circuit essential for vocal learning. We
      have examined the activity of identified HVC neurons of zebra finches during
      singing. Antidromic activation was used to identify three classes of HVC cells:
      neurons projecting to the premotor nucleus RA, neurons projecting to area X in
      the AFP, and putative HVC interneurons. HVC interneurons are active throughout
      the song and display tonic patterns of activity. Projection neurons exhibit
      highly phasic stereotyped firing patterns. X-projecting (HVC((X))) neurons burst
      zero to four times per motif, whereas RA-projecting neurons burst extremely
      sparsely--at most once per motif. The bursts of HVC projection neurons are
      tightly locked to the song and typically have a jitter of <1 ms. Population
      activity of interneurons, but not projection neurons, was significantly
      correlated with syllable patterns. Consistent with the idea that HVC codes for
      the temporal order in the song rather than for sound, the vocal dynamics and
      neural dynamics in HVC occur on different and uncorrelated time scales. We test
      whether HVC((X)) neurons are auditory sensitive during singing. We recorded the
      activity of these neurons in juvenile birds during singing and found that firing
      patterns of these neurons are not altered by distorted auditory feedback, which
      is known to disrupt learning or to cause degradation of song already learned.

PMID- 17182907
TI  - Bayesian analysis of interleaved learning and response bias in behavioral
      experiments.
AB  - Accurate characterizations of behavior during learning experiments are essential
      for understanding the neural bases of learning. Whereas learning experiments
      often give subjects multiple tasks to learn simultaneously, most analyze subject
      performance separately on each individual task. This analysis strategy ignores
      the true interleaved presentation order of the tasks and cannot distinguish
      learning behavior from response preferences that may represent a subject's biases
      or strategies. We present a Bayesian analysis of a state-space model for
      characterizing simultaneous learning of multiple tasks and for assessing
      behavioral biases in learning experiments with interleaved task presentations.
      Under the Bayesian analysis the posterior probability densities of the model
      parameters and the learning state are computed using Monte Carlo Markov Chain
      methods. Measures of learning, including the learning curve, the ideal observer
      curve, and the learning trial translate directly from our previous likelihood
      based state-space model analyses. We compare the Bayesian and current likelihood
      based approaches in the analysis of a simulated conditioned T-maze task and of an
      actual object-place association task. Modeling the interleaved learning feature
      of the experiments along with the animal's response sequences allows us to
      disambiguate actual learning from response biases. The implementation of the
      Bayesian analysis using the WinBUGS software provides an efficient way to test
      different models without developing a new algorithm for each model. The new state
      space model and the Bayesian estimation procedure suggest an improved,
      computationally efficient approach for accurately characterizing learning in
      behavioral experiments.

PMID- 17182908
TI  - Bayesian filtering of myoelectric signals.
AB  - Surface electromyography is used in research, to estimate the activity of muscle,
      in prosthetic design, to provide a control signal, and in biofeedback, to provide
      subjects with a visual or auditory indication of muscle contraction.
      Unfortunately, successful applications are limited by the variability in the
      signal and the consequent poor quality of estimates. I propose to use a nonlinear
      recursive filter based on Bayesian estimation. The desired filtered signal is
      modeled as a combined diffusion and jump process and the measured
      electromyographic (EMG) signal is modeled as a random process with a density in
      the exponential family and rate given by the desired signal. The rate is
      estimated on-line by calculating the full conditional density given all past
      measurements from a single electrode. The Bayesian estimate gives the filtered
      signal that best describes the observed EMG signal. This estimate yields results
      with very low short-time variability but also with the capability of very rapid
      response to change. The estimate approximates isometric joint torque with lower
      error and higher signal-to-noise ratio than current linear methods. Use of the
      nonlinear filter significantly reduces noise compared with current algorithms,
      and it may therefore permit more effective use of the EMG signal for prosthetic
      control, biofeedback, and neurophysiology research.

PMID- 17182909
TI  - Neural coding mechanisms for flow rate in taste-responsive cells in the nucleus
      of the solitary tract of the rat.
AB  - When a taste stimulus enters the mouth, intentional movement of the stimulus
      within the oropharyngeal cavity affects the rate at which taste receptors are
      exposed to the stimulus and may ultimately affect taste perception. Early studies
      have shown that stimulus flow rate, the experimental equivalent of the effects of
      these investigative movements, modulates the portion of the peripheral nerve
      response that occurs when behavioral assessments of tastants are made. The
      present experiment studied the neural coding mechanisms for flow rate in the
      nucleus of the solitary tract (NTS), the first central relay in the taste
      pathway. Responses to NaCl (0.1 M) presented at high (5 ml/s) and low (3 ml/s)
      flow rates, sucrose (0.5 M), quinine HCl (0.01 M), and HCl (0.01 M) were recorded
      extracellularly from single NTS units in multiple replications. Information
      conveyed by evoked responses was analyzed with a family of metrics that quantify
      the similarity of two spike trains in terms of spike count and spike timing.
      Information about flow rate was conveyed by spike timing and spike count in
      approximately equal proportions of units (each approximately 1/3), whereas
      information about taste quality was conveyed by spike timing in about half of the
      units. Different subsets of units contributed information for discrimination of
      flow rate and taste quality.

PMID- 17182910
TI  - Modulation of voltage-gated Ca2+ current in vestibular hair cells by nitric
      oxide.
AB  - The structural elements of the nitric oxide-cyclic guanosine monophosphate (NO
      cGMP) signaling pathway have been described in the vestibular peripheral system.
      However, the functions of NO in the vestibular endorgans are still not clear. We
      evaluated the action of NO on the Ca(2+) currents in hair cells isolated from the
      semicircular canal crista ampullaris of the rat (P14-P18) by using the whole cell
      and perforated-cell patch-clamp technique. The NO donors 3-morpholinosydnonimine
      (SIN-1), sodium nitroprusside (SNP), and (+/-)-(E)-4-ethyl-2-[(Z)-hydroxyimino]-5
      nitro-3-hexen-1-yl-nicotinamide (NOR-4) inhibited the Ca(2+) current in hair
      cells in a voltage-independent manner. The NO scavenger 2-(4-carboxyphenyl)
      4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO) prevented the inhibitory
      effect of SNP on the Ca(2+) current. The selective inhibitor of the soluble form
      of the enzyme guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1
      one (ODQ), also decreased the SNP-induced inhibition of the Ca(2+) current. The
      membrane-permeant cGMP analogue 8-Br-cGMP mimicked the SNP effect. KT-5823, a
      specific inhibitor of cGMP-dependent protein kinase (PGK), prevented the
      inhibition of the Ca(2+) current by SNP and 8-Br-cGMP. In the presence of N
      ethylmaleimide (NEM), a sulfhydryl alkylating agent that prevents the S
      nitrosylation reaction, the SNP effect on the Ca(2+) current was significantly
      diminished. These results demonstrated that NO inhibits in a voltage-independent
      manner the voltage-activated Ca(2+) current in rat vestibular hair cells by the
      activation of a cGMP-signaling pathway and through a direct action on the channel
      protein by a S-nitrosylation reaction. The inhibition of the Ca(2+) current by NO
      may contribute to the regulation of the intracellular Ca(2+) concentration and
      hair-cell synaptic transmission.

PMID- 17182911
TI  - Laminar population analysis: estimating firing rates and evoked synaptic activity
      from multielectrode recordings in rat barrel cortex.
AB  - We present a new method, laminar population analysis (LPA), for analysis of
      laminar-electrode (linear multielectrode) data, where physiological constraints
      are explicitly incorporated in the mathematical model: the high-frequency band
      [multiunit activity (MUA)] is modeled as a sum over contributions from firing
      activity of multiple cortical populations, whereas the low-frequency band [local
      field potential (LFP)] is assumed to reflect the dendritic currents caused by
      synaptic inputs evoked by this firing. The method is applied to stimulus-averaged
      laminar-electrode data from barrel cortex of anesthetized rat after single
      whisker flicks. Two sample data sets, distinguished by stimulus paradigm, type of
      applied anesthesia, and electrical boundary conditions, are studied in detail.
      These data sets are well accounted for by a model with four cortical populations:
      one supragranular, one granular, and two infragranular populations. Population
      current source densities (CSDs; the CSD signatures after firing in a particular
      population) provided by LPA are further used to estimate the synaptic connection
      pattern between the various populations using a new LFP template-fitting
      technique, where LFP population templates are found by the electrostatic forward
      solution based on results from compartmental modeling of morphologically
      reconstructed neurons. Our analysis confirms previous experimental findings
      regarding the synaptic connections from neurons in the granular layer onto
      neurons in the supragranular layers and provides predictions about other synaptic
      connections. Furthermore, the time dependence of the stimulus-evoked population
      firing activity is predicted, and the temporal ordering of response onset is
      found to be compatible with earlier findings.

PMID- 17182912
TI  - Skill representation in the primary motor cortex after long-term practice.
AB  - The acquisition of motor skills can lead to profound changes in the functional
      organization of the primary motor cortex (M1). For example, performance of
      movement sequences after prolonged practice is associated with an expansion of
      the effector representation in M1. Paradoxically, there is little evidence that
      the activity of M1 neurons reflects acquired skills, especially sequences of
      movements. We examined the activity of M1 neurons during skilled movement
      sequences in macaques trained to successively hit targets on a monitor. The
      targets appeared either pseudorandomly (Random mode) or in one of two repeating
      sequences (Repeating mode). With practice, response times for repeating sequences
      substantially declined and the monkeys performed the task predictively. Highly
      trained animals retained the acquired skill after long gaps in practice. After >2
      yr of training, 40% of M1 neurons were differentially active during the two task
      modes. Variations in movement kinematics did not fully explain the task-dependent
      modulation of neuron activity. Differentially active neurons were more strongly
      influenced by task mode than by kinematics. Our results suggest that practice
      sculpts the response properties of M1 neurons. M1 may be a site of storage for
      the internal representation of skilled sequential movements.

PMID- 17182913
TI  - Responses of single neurons in monkey amygdala to facial and vocal emotions.
AB  - The face and voice can independently convey the same information about emotion.
      When we see an angry face or hear an angry voice, we can perceive a person's
      anger. These two different sensory cues are interchangeable in this sense.
      However, it is still unclear whether the same group of neurons process signals
      for facial and vocal emotions. We recorded neuronal activity in the amygdala of
      monkeys while watching nine video clips of species-specific emotional
      expressions: three monkeys showing three emotional expressions (aggressive
      threat, scream, and coo). Of the 227 amygdala neurons tested, 116 neurons (51%)
      responded to at least one of the emotional expressions. These "monkey-responsive"
      neurons-that is, neurons that responded to monkey-specific emotional expression
      preferred the scream to other emotional expressions irrespective of identity. To
      determine the element crucial to neuronal responses, the activity of 79 monkey
      responsive neurons was recorded while a facial or vocal element of a stimulus was
      presented alone. Although most neurons (61/79, 77%) strongly responded to the
      visual but not to the auditory element, about one fifth (16/79, 20%) maintained a
      good response when either the facial or vocal element was presented. Moreover,
      these neurons maintained their stimulus-preference profiles under facial and
      vocal conditions. These neurons were found in the central nucleus of the
      amygdala, the nucleus that receives inputs from other amygdala nuclei and in turn
      sends outputs to other emotion-related brain areas. These supramodal responses to
      emotion would be of use in generating appropriate responses to information
      regarding either facial or vocal emotion.

PMID- 17182914
TI  - NK-1 receptors modulate the excitability of ON cells in the rostral ventromedial
      medulla.
AB  - The role of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla
      (RVM) was studied using extracellular single-unit recording combined with
      microiontophoresis. In rats, on- and off-type neurons were identified using
      noxious heat or mechanical stimuli applied to the tail. Responses evoked by
      iontophoretic application of N-methyl-d-aspartate (NMDA) were determined before
      and after intraplantar injection of capsaicin or iontophoretic application of
      substance P. In off cells, capsaicin produced an extended pause in ongoing
      activity but did not alter the subsequent spontaneous discharge rate or NMDA
      evoked responses. In contrast, spontaneous discharge rates of on cells increased
      after capsaicin, and their responses to NMDA increased >100% above control
      values. The increased responses to NMDA after capsaicin were attenuated by
      iontophoretic application of the selective NK-1 receptor antagonist L-733,060.
      Similarly to capsaicin, iontophoretic application of the selective NK-1 receptor
      agonist, [Sar(9),Met(O(2))(11)]-substance P (SM-SP), increased the spontaneous
      discharge rate and NMDA-evoked responses of on cells by >100% of control values.
      These effects were antagonized by L-733,060. Immunohistochemical studies showed
      that a subset of neurons in the RVM labeled NK-1 receptors and that nearly all of
      these neurons were immunoreactive for the NMDAR1 subunit of the NMDA receptor.
      These results demonstrate that activation of NK-1 receptors in the RVM enhances
      responses of on cells evoked by NMDA. It is suggested that activation of NK-1
      receptors in the RVM and the ensuing sensitization of on cells may contribute to
      the development of central sensitization and hyperalgesia after tissue injury and
      inflammation.

PMID- 17182915
TI  - Acute clozapine suppresses synchronized pyramidal synaptic network activity by
      increasing inhibition in the ferret prefrontal cortex.
AB  - Recent studies have indicated that impaired neural circuitry in the prefrontal
      cortex is a prominent feature of the neuropathology of schizophrenia. Clozapine
      is one of the most effective antipsychotic drugs used for this debilitating
      disease. Despite its effectiveness, the mechanism by which clozapine acts on
      prefrontal cortical circuitry remains poorly understood. In this study, in vitro
      multiple whole cell recordings were performed in slices of the ferret prefrontal
      cortex. Clozapine, which effectively inhibited the spontaneous synchronized
      network activities in the prefrontal neurons, achieved the suppressive effect by
      decreasing the recurrent excitation among pyramidal neurons and by enhancing the
      inhibitory inputs onto pyramidal cells through a likely network mechanism.
      Indeed, under the condition of disinhibition, the depressing effects were
      reversed and clozapine enhanced the recurrent excitation. These results suggest
      that the therapeutic actions of clozapine in alleviating the positive symptoms of
      schizophrenia are achieved, at least partially, through the readjustment of
      synaptic balance between the excitation and inhibition in the prefrontal cortical
      circuitry.

PMID- 17182916
TI  - Subthalamic and striatal neurons concurrently process motor, limbic, and
      associative information in rats performing an operant task.
AB  - Although the subthalamic nucleus (STN) is commonly assumed to be a relay for
      striatal (STR) output, anatomical evidence suggests the two structures are
      connected in parallel, raising the possibility that parallel STN and STR firing
      patterns mediate behavioral processes. The STR is known to play a role in
      associative and limbic processes, and although behavioral studies suggest that
      the STN may do so as well, evaluation of this hypothesis is complicated by a lack
      of pertinent STN physiological data. We recorded concurrent STN and STR firing
      patterns in rats learning an operant nose-poke task. Both structures responded in
      similar proportions to task events including instructive cues, discriminative
      nose-pokes, and sucrose reinforcement. Neuronal responses to reinforcement
      comprised phasic excitations preceding reinforcement and inhibitions afterward;
      the inhibition was attenuated when reinforcement was absent. Reinforcement
      responses occurred more frequently during later training sessions in which
      discriminative action was required, suggesting that responses were context
      dependent. Nose-pokes were typically preceded by excitations; there also was a
      nonsignificant trend toward inhibition encoding correct nose-pokes. Sustained
      changes in firing rate coinciding with specific task events suggested that both
      nuclei were encoding behavioral sequences; this is the first report of such
      behavior in the STN. Our findings also reveal complex STN responses to
      reinforcement. Thus both STN and STR neurons show concurrent involvement in
      motor, limbic, and associative processes.

PMID- 17182917
TI  - Epidemiology of aortic aneurysm repair in the United States from 1993 to 2003.
AB  - The epidemiology of abdominal aortic aneurysm (AAA) disease has been well
      described over the preceding 50 years. This disease primarily affects elderly
      males with smoking, hypertension, and a positive family history contributing to
      an increased risk of aneurysm formation. The aging population as well as
      increased screening in high-risk populations has led some to suggest that the
      incidence of AAAs is increasing. The National Inpatient Sample (1993-2003), a
      national representative database, was used in this study to determine trends in
      mortality following AAA repair in the United States. In addition, the impact of
      the introduction of less invasive endovascular AAA repair was assessed. Overall
      rates of treated unruptured and ruptured AAAs remained stable (unruptured 12 to
      15/100,000; ruptured 1 to 3/100,000). In 2003, 42.7% of unruptured and 8.8% of
      ruptured AAAs were repaired through an endovascular approach. Inhospital
      mortality following unruptured AAA repair continues to decline for open repair
      (5.3% to 4.7%, P = 0.007). Mortality after elective endovascular AAA repair also
      has statistically decreased (2.1% to 1.0%, P = 0.024) and remains lower than open
      repair. Mortality rates for ruptured AAAs following repair remain high (open:
      46.5% to 40.7%, P = 0.01; endovascular: 40.0% to 35.3%, P = 0.823). These data
      suggest that the numbers of patients undergoing elective AAA repair have remained
      relatively stable despite the introduction of less invasive technology. A shift
      in the treatment paradigm is occurring with a higher percentage of patients
      subjected to elective endovascular AAA repair compared to open repair. This
      shift, at least in the short term, appears justified as the mortality in patients
      undergoing elective endovascular AAA repair is significantly reduced compared to
      patients undergoing open AAA repair.

PMID- 17182918
TI  - A biomechanics-based rupture potential index for abdominal aortic aneurysm risk
      assessment: demonstrative application.
AB  - Abdominal aortic aneurysms (AAAs) can typically remain stable until the strength
      of the aortic wall is unable to withstand the forces acting on it as a result of
      the luminal blood pressure, resulting in AAA rupture. The clinical treatment of
      AAA patients presents a dilemma for the surgeon: surgery should only be
      recommended when the risk of rupture of the AAA outweighs the risks associated
      with the interventional procedure. Since AAA rupture occurs when the stress
      acting on the wall exceeds its strength, the assessment of AAA rupture should
      include estimates of both wall stress and wall strength distributions. The
      present work details a method for noninvasively assessing the rupture potential
      of AAAs using patient-specific estimations the rupture potential index (RPI) of
      the AAA, calculated as the ratio of locally acting wall stress to strength. The
      RPI was calculated for thirteen AAAs, which were broken up into ruptured (n = 8
      and nonruptured (n = 5) groups. Differences in peak wall stress, minimum strength
      and maximum RPI were compared across groups. There were no statistical
      differences in the maximum transverse diameters (6.8 +/- 0.3 cm vs. 6.1 +/- 0.5
      cm, p = 0.26) or peak wall stress (46.0 +/- 4.3 vs. 49.9 +/- 4.0 N/cm(2), p =
      0.62) between groups. There was a significant decrease in minimum wall strength
      for ruptured AAA (81.2 +/- 3.9 and 108.3 +/- 10.2 N/cm(2), p = 0.045). While the
      differences in RPI values (ruptured = 0.48 +/- 0.05 vs. nonruptured = 0.36 +/-
      0.03, respectively; p = 0.10) did not reach statistical significance, the p-value
      for the peak RPI comparison was lower than that for both the maximum diameter (p
      = 0.26) and peak wall stress (p = 0.62) comparisons. This result suggests that
      the peak RPI may be better able to identify those AAAs at high risk of rupture
      than maximum diameter or peak wall stress alone. The clinical relevance of this
      method for rupture assessment has yet to be validated, however, its success could
      aid clinicians in decision making and AAA patient management.

PMID- 17182919
TI  - The long-term relationship of wall stress to the natural history of abdominal
      aortic aneurysms (finite element analysis and other methods).
AB  - For the past four decades, abdominal aortic aneurysm (AAA) rupture risk has been
      estimated using maximum aneurysm diameter. Although this works relatively well in
      general, clinicians know that some aneurysms rupture at an unusually small size,
      while others grow to exceptionally large sizes without rupture. We have
      demonstrated that finite element analysis (FEA) of AAA wall stress using three
      dimensional computed tomography (CT) reconstructions is better than diameter for
      differentiating AAAs near the time of rupture, and that wall stress is superior
      to AAA diameter for predicting rupture risk in patients under observation. This
      article summarizes our current work, future areas of investigation, and issues
      related to "translational" research for FEA of aortic aneurysms.

PMID- 17182920
TI  - A summary of the contributions of the VA cooperative studies on abdominal aortic
      aneurysms.
AB  - The Department of Veterans Affairs Cooperative Studies Program has completed two
      studies on abdominal aortic aneurysm (AAA) and is currently conducting a third.
      The first, the Aneurysm Detection and Management (ADAM) Study, consisted of both
      a screening program, which provided information on the prevalence and
      associations of AAA, and a randomized trial, which found that survival is not
      improved by repair of small AAA. The second was a prospective observational study
      to determine the incidence of rupture in patients with large AAA for whom
      elective repair was not planned due to medical contraindications or patient
      refusal. AAA in this population had a high risk of rupture, about 10% per year
      for AAA > 5.5 cm, and 25% within 6 months for AAA larger than 8.0 cm. The third,
      the Open Versus Endovascular Repair (OVER) Trial, is a multicenter randomized
      trial comparing long-term survival following two methods of elective AAA repair.

PMID- 17182921
TI  - Pharmacological approaches to prevent abdominal aortic aneurysm enlargement and
      rupture.
AB  - Current efforts to limit the mortality from abdominal aortic aneurysm (AAA) are
      dependent on detection and elective repair. Even by conservative estimates, there
      are more than 300,000 undetected AAAs in the United States, most of which are
      small and would not require immediate intervention. Current practice following
      detection of a small AAA includes education, risk factor management, and serial
      observation. This approach, based on the statistical probability of death from
      rupture compared to the morbidity and mortality of repair, can be unsettling to
      patients and lead to a decline in perceived quality of life. While the
      pathophysiology of AAA is not completely understood, observations from human
      tissues and animal studies have identified a number of potential targets for
      inhibiting aneurysm expansion. It is clear that the prominent inflammatory
      response identified in aneurysm tissue has a role in promoting aortic expansion.
      This inflammatory response is thought to account for increased expression of
      proteolytic enzymes. Recent work has suggested a unifying hypothesis centered on
      the MAP kinase family affecting both the regulation of matrix synthesis and the
      expression of proteolytic enzymes. The tetracycline antibiotics and
      antihypertensive medications that affect the angiotensin-converting enzyme system
      can inhibit proteolysis. There are adequate preliminary data to support a large
      prospective randomized trial of doxycycline to prevent aneurysm expansion.

PMID- 17182922
TI  - Should usual criteria for intervention in abdominal aortic aneurysms be
      "downsized," considering reported risk reduction with endovascular repair?
AB  - Two randomized trials have demonstrated the safety of waiting until abdominal
      aortic aneurysm (AAA) diameter reaches 5.5 cm for repair in most patients. Other
      recent randomized trials have demonstrated lower perioperative mortality and
      morbidity with endovascular aneurysm repair (EVAR) compared to open surgery.
      Therefore, it is logical to assume that endovascular repair may change the
      appropriate threshold for intervention. However, endovascular repair is not as
      durable as open surgery and is associated with ongoing risks of rupture and
      reintervention. Decision analysis based on data available in 1998 showed that
      endovascular repair should not change the threshold for intervention. Since that
      time retrospective data have emerged to suggest that outcomes with endovascular
      repair are improved in smaller AAAs, although this may simply represent selection
      bias and the natural history of small AAAs. Randomized trials are appropriate to
      determine whether improved endovascular outcomes in small AAAs reduce late
      rupture and reintervention enough to justify early intervention in patients with
      appropriate anatomy. In the absence of data from these trials, the threshold for
      intervention should not be changed.

PMID- 17182923
TI  - Pathophysiology of abdominal aortic aneurysms: insights from the elastase-induced
      model in mice with different genetic backgrounds.
AB  - Abdominal aortic aneurysms (AAAs) represent a complex degenerative disorder
      involving chronic aortic wall inflammation and destructive remodeling of
      structural connective tissue. Studies using human AAA tissues have helped
      identify a variety of molecular mediators and matrix-degrading proteinases, which
      contribute to aneurysm disease, thereby providing a sound foundation for
      understanding AAAs; however, these human tissue specimens represent only the "end
      stage" of a long and progressive disease process. Further progress in
      understanding the pathophysiology of AAAs is therefore dependent in part on the
      development and application of effective animal models that recapitulate key
      aspects of the disease. Based on original studies in rats, transient perfusion of
      the abdominal aorta with porcine pancreatic elastase has provided a reproducible
      and robust model of AAAs. More recent applications of this model to mice have
      also opened new avenues for investigation. In this review, we summarize
      investigations using the elastase-induced mouse model of AAAs including results
      in animals with targeted deletion of specific genes and more general differences
      in mice on different genetic backgrounds. These studies have helped us identify
      genes that are essential to the development of AAAs (such as MMP9, IL6, and AT1R)
      and to reveal other genes that may be dispensable in aneurysm formation.
      Investigations on mice from different genetic backgrounds are also beginning to
      offer a novel approach to evaluate the genetic basis for susceptibility to
      aneurysm development.

PMID- 17182924
TI  - Regression of abdominal aortic aneurysm by inhibition of c-Jun N-terminal kinase
      in mice.
AB  - Abdominal aortic aneurysm (AAA) is a common disease that, when surgical treatment
      is inapplicable, results in rupture of the aorta with high mortality. Although
      nonsurgical treatment for AAA is eagerly awaited, the destruction of the aortic
      walls in AAA has been considered an irreversible process. We found that c-Jun N
      terminal kinase (JNK) is highly activated in human AAA walls. We also found that
      JNK activity is essential for the expression of matrix metalloproteinase (MMP)-9
      and, concurrently, suppression of the extracellular matrix (ECM) biosynthesis. We
      therefore investigated the role of JNK in the pathogenesis of AAA in vivo. We
      created a mouse AAA model by periaortic application of CaCl(2), which was
      accompanied by activation of JNK and MMPs, and suppression of lysyl oxidase
      (LOX), which is an essential biosynthetic enzyme for collagen and elastin fibers.
      Our data indicate that, in addition to MMP activities, suppression of ECM
      biosynthesis may contribute to the AAA pathogenesis because local LOX gene
      delivery prevented AAA formation. Treatment of mice with SP600125, a specific JNK
      inhibitor, completely abrogated the formation of CaCl(2)-induced AAA.
      Furthermore, SP600125 treatment after the establishment of AAA caused a reduction
      in the aortic diameters with normalized tissue architecture. SP600125 treatment
      also caused significant regression of angiotensin II-induced AAA in ApoE-null
      mice after its establishment, as demonstrated by serial ultrasonographic studies
      in live animals. These data demonstrate that JNK dictates the abnormal ECM
      metabolism in AAA pathogenesis by enhancing tissue degradation and suppressing
      tissue repair. Therefore, inhibition of JNK may provide a novel therapeutic
      option for AAA.

PMID- 17182925
TI  - Role of the renin-angiotensin system in the development of abdominal aortic
      aneurysms in animals and humans.
AB  - The mediators for the initiation, progression, and rupture of abdominal aortic
      aneurysms (AAAs) have not been defined. Recent evidence has demonstrated that
      chronic infusion of angiotensin II via subcutaneously placed osmotic pumps can
      reproducibly form AAAs in mice. The evolution of AngII-induced AAAs in these mice
      is complex. Rapid medial macrophage accumulation precedes transmedial breaks and
      large lumen expansion, which are restricted to the suprarenal aorta. After this
      initial phase, there is a more gradual rate of lumen expansion that is
      progressive with continued AngII exposure. There is extensive aortic remodeling
      during this gradual expansion phase. An initial prominent thrombus gradually
      resolves and is replaced by fibrous tissue containing several types of
      inflammatory cells. At prolonged intervals of AngII infusion, internal aortic
      diameters of the suprarenal aorta can increase up to fourfold compared to the
      same region in saline-infused mice. The extrapolation of these data in mice to
      the development of human AAAs remains to be determined. However, there are a
      considerable number of drugs available to potentially test the efficacy of
      inhibiting the renin-angiotensin system on the progression of the human disease.

PMID- 17182926
TI  - AAA disease: mechanism, stratification, and treatment.
AB  - Abdominal aortic aneurysm (AAA) is a common and frequently lethal disease of
      older Americans. No medical therapy has been proven effective in retarding
      progression of small AAAs prior to surgical repair. With the emerging ability of
      magnetic resonance (MR) flow imaging and MR-based computational analysis to
      define aortic hemodynamic conditions, and bio-imaging strategies to monitor
      aortic inflammation real time in vivo, the opportunity now exists to confirm the
      potential value of medical interventions such as supervised exercise training as
      first line therapy for small AAA disease.

PMID- 17182927
TI  - Refinements in mathematical models to predict aneurysm growth and rupture.
AB  - The growth of aneurysms and eventually their likelihood of rupture depend on the
      determination of the stress and strain within the aneurysm wall and the exact
      reproduction of its geometry. A numerical model is developed to analyze pulsatile
      flow in abdominal aortic aneurysm (AAA) models using real physiological resting
      and exercise waveforms. Both laminar and turbulent flows are considered.
      Interesting features of the flow field resulting from using realistic
      physiological waveforms are obtained for various parameters using finite element
      methods. Such parameters include Reynolds number, size of the aneurysm (D/d), and
      flexibility of the aneurysm wall. The effect of non-Newtonian behavior of blood
      on hemodynamic stresses is compared with Newtonian behavior, and the non
      Newtonian effects are demonstrated to be significant in realistic flow
      situations. Our results show that maximum turbulent fluid shear stress occurs at
      the distal end of the AAA model. Furthermore, turbulence is found to have a
      significant effect on the pressure distribution along AAA wall for both
      physiological waveforms. Related experimental work in which a bench top aneurysm
      model is developed is also discussed. The experimental model provides a platform
      to validate the numerical model. This work is part of our ongoing development of
      a patient-specific tool to guide clinician decision making and to elucidate the
      contribution of blood flow-induced stresses to aneurysm growth and eventual
      rupture. These studies indicate that accurately modeling the physiologic features
      of real aneurysms and blood is paramount to achieving our goal.

PMID- 17182928
TI  - Abdominal aortic aneurysm as a complex multifactorial disease: interactions of
      polymorphisms of inflammatory genes, features of autoimmunity, and current status
      of MMPs.
AB  - The role of matrix metalloproteinases (MMPs) in the pathogenesis of abdominal
      aortic aneurysm (AAA) has focused on the degradation of the extracellular matrix
      (ECM). The new frontier of MMP biology involves the role of MMPs in releasing
      cryptic fragments and neoepitopes from the ECM and the impact of MMPs on the
      regulation of the inflammatory response. The ECM is a complex structure, much
      more important than an inert scaffold. Both MMP-2 and MMP-9 expose a cryptic
      epitope that controls angiogenesis. MMPs inhibit angiogenesis through the release
      of endostatin, endorepellin, arresten, canstatin, and tumstatin. Other breakdown
      products of the ECM include fragments of fragmin and elastin degradation products
      (EDPs). In addition, the ECM contains embedded vascular endothelial growth factor
      (VEGF) and transforming growth factor-beta (TGF-beta). Inflammation is a complex,
      highly regulated system that involves the identification of injury or infection,
      response to the injury or infection, repair and healing, and return to normal
      homeostasis. In some instances, the inflammatory process leads to a pathologic
      process that is damaging to the host. MMPs play an important role in the control
      of the inflammatory response through the modification of proinflammatory
      cytokines, chemokines, and shedding of membrane receptors. Genetic association
      studies have been performed to help determine the genetic risk associated with
      certain single nucleotide polymorphisms (SNPs) However, because of the
      variability in the patient populations and the size of the population, it is
      difficult to draw any conclusions from these studies. While the etiology of AAA
      remains unknown, understanding of the inflammatory process and its regulatory
      points will develop new strategies for the treatment of AAA. Perhaps one
      difficulty with understanding the pathogenesis of AAA is the lack of precise
      definition of the phenotype.

PMID- 17182929
TI  - The intraluminal thrombus as a source of proteolytic activity.
AB  - Most abdominal aortic aneurysms (AAAs) with a diameter indicating need for
      surgical repair contain intraluminal thrombus (ILT). The development of AAA is
      linked to degradation of elastin and collagen. These changes are more pronounced
      in the aneurysm wall covered by the ILT, which also shows more signs of
      inflammation and is thinner compared to the aneurysm wall exposed to flowing
      blood. The rate of increase in diameter of AAA correlates with increased thrombus
      growth and rupture. CT examinations of patients with rupture have demonstrated
      contrast appearing in the thrombus suggesting bleeding into it. Studies using
      gene array of human aneurysm specimens have shown that most matrix
      metalloproteinases (MMP) were upregulated in the thrombus-free wall. Analyses by
      zymography, however, demonstrate gelatinase activity in the interface between the
      thrombus and the underlying wall and in the media of the wall not covered by a
      thrombus. The thrombus contains large amounts of neutrophils. Neutrophil
      gelatinase associated lipocalin (NGAL) is involved in the regulation of MMP-9
      activity and prevents its inactivation, thus augmenting the proteolytic effect.
      It has been identified in all layers of the ILT. The presence of NGAL/MMP-9
      complexes throughout the thrombus and in the thrombus-covered wall may contribute
      to the increased proteolytic degradation seen in this wall segment. In
      conclusion, the presence, growth, and thickness of the ILT have been shown to be
      associated with growth and risk of rupture. The wall underlying the thrombus is
      thinner and shows more signs of proteolytic degradation. Increased proteolytic
      activity by MMP-9 may be mediated by binding to NGAL.

PMID- 17182930
TI  - Activators of plasminogen and the progression of small abdominal aortic
      aneurysms.
AB  - The aim of this study was to examine the role of activating pathways of
      plasminogen in the natural history of abdominal aortic aneurysms (AAA). To
      fulfill this objective 70 male patients with small AAA (> 3 cm) were interviewed
      and examined. Their blood samples were taken at diagnosis. The patients were
      scanned annually for a minimum period of 1 year and a maximum of 5 years (mean
      2.5 years), and referred for surgery if the AAA exceeded 5 cm in diameter. Plasma
      levels of urokinase-like plasminogen activator (uPA), tissue-type plasminogen
      activator (tPA), plasminogen-activator-inhibitor-1 (PAI-1), macrophage-inhibiting
      factor (MIF), transforming-growth-factor-beta1 (TGF-beta1), homocysteine, and
      serum levels of IgA-antibodies against Chlamydia pneumoniae (IgA-CP) and cotinine
      (a nicotine metabolite) were measured. The annual expansion rate correlated
      positively with tPA, IgA-CP, and S-cotinine; rho = 0.37 (P = 0.004), 0.28 (P =
      0.01), and 0.24 (P = 0.04), while PAI-1, uPA, TGF-beta1, homocysteine, and MIF
      did not. S-cotinine and PAI-1 also correlated positively with tPA, rho = 0.24 (P
      = 0.04), and 0.33 (P = 0.005). IgA-CP did not correlate with tPA. By receiver
      operating characteristics (ROC) curve analysis, tPA showed to be predictive of
      cases expanding to above 5 cm within the first 5 years with an optimal
      sensitivity and specificity of 0.73 and 0.71, respectively (P = 0.015). The
      aortic matrix degradation in AAA may be partly caused by an activation of
      plasminogen by tPA, but not by uPA, which usually dominates matrix degradation.
      Smoking seems to be an important factor for this pathway, while the pathway of
      IgA-CP seems different.

PMID- 17182931
TI  - Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm
      development in apolipoprotein E-deficient mice?
AB  - Activation of the 5-lipoxygenase (5-LO) pathway leads to the biosynthesis of
      proinflammatory leukotriene (LT) lipid mediators in macrophages, mast cells, and
      other inflammatory cell types. A recent surge in interest in this pathway within
      the cardiovascular system has arisen from a variety of exciting findings using
      genetic, pathological specimen, and biochemical approaches in humans and mice. We
      found that a subset of CD68-positive macrophages, localized within the
      adventitial layer of apolipoprotein E (apo E)-deficient mice, expressed 5-LO and
      that these cells represented a significant cellular component of aortic aneurysms
      induced by an atherogenic diet containing cholate. Surprisingly, almost no 5-LO
      expressing cells were observed in atherosclerotic lesions in the same mice.
      Correspondingly, lesion size in the fat-fed mice did not depend on 5-LO gene
      expression but aneurysm incidence was reduced in the absence of the 5-LO pathway.
      We are currently exploring the potential mechanisms for 5-LO/LT involvement in
      aneurysm pathogenesis and if this pathway might come into play in other models
      such as induction by angiotensin II.

PMID- 17182933
TI  - Matrix metalloproteinase-2: the forgotten enzyme in aneurysm pathogenesis.
AB  - The pathogenesis of abdominal aortic aneurysm (AAAs) involves progressive cycles
      of proteolysis and inflammation, the product of proteolysis driving subsequent
      inflammation. Little is yet known about the initiating events. We review the
      specific literature examining the possibility that MMP-2 may be the initial
      catalyst. Histologically, elastolysis is one of the earliest observable events in
      aneurysm genesis. Matrix metalloproteinase-2 (MMP-2), as the dominant gelatinase
      differentially expressed in aneurysmal tissue and cells derived from aneurysms,
      would be a good candidate. We report the results of in vivo and in vitro
      experiments, which lend support to the importance of MMP-2 as an aneurysmal
      initiator.

PMID- 17182932
TI  - Do cathepsins play a role in abdominal aortic aneurysm pathogenesis?
AB  - Between 1998 and 1999 we suggested a role for cysteine proteases, particularly
      cathepsins S and K, in atherosclerosis and abdominal aortic aneurysm (AAA)
      formation. We also demonstrated the presence and activity of cathepsins S, K, and
      L in atherosclerotic and aneurysmal lesions in humans. Features unique to this
      family of extracellular enzymes indicate its likely participation in these
      vascular diseases. As very potent elastolytic enzymes, cathepsins are strong
      candidates as key participants in aneurysm development. Importantly, cathepsins
      express very high elastolytic activity in AAA due to reciprocal correlation with
      cystatin C, their most abundant endogenous inhibitor. Two opposite processes
      coexist in aneurysmal tissue: overexpression of elastolytic cathepsins, and
      severe suppression of cystatin C, probably due to differentially regulated
      expression and secretion of cathepsins and their inhibitors in response to
      inflammatory cytokines. Involvement of cathepsins in microvessel formation, a
      pathophysiological marker of human AAA, and programmed cell death (apoptosis),
      increases the likelihood of cathepsin participation in AAA formation and growth.
      We also summarize here results obtained in our and other laboratories that
      demonstrated reduced atherosclerosis and AAA in in vivo models using mice lacking
      different cathepsins. Deficiency of cysteine protease inhibitor cystatin C in
      atherosclerosis-prone ApoE-null mice leads to the development of specific
      features of AAA such as thinning of the tunica media and aortic dilatation. Taken
      together, such findings in humans in vitro with different cell types and in vivo
      in genetically altered mice demonstrate the importance of cysteine
      protease/protease inhibitor balance in dysregulated arterial integrity and
      remodeling during atherosclerosis and aortic aneurysm formation.

PMID- 17182934
TI  - Current status of endovascular repair of infrarenal abdominal aortic aneurysms in
      the context of 50 years of conventional repair.
AB  - The operative risk for conventional open repair of nonruptured infrarenal
      abdominal aortic aneurysms (AAAs) has steadily declined during the past several
      decades to the point that open procedures now can be done with a mortality rate
      of approximately 2% at tertiary referral centers. Nevertheless, population-based
      studies suggest that the mortality rate for open AAA repair remains nearly 7% in
      many communities, a finding that undoubtedly is influenced by a substantial risk
      for unfavorable outcomes in patients who represent less than ideal candidates for
      major abdominal operations on the basis of advanced age and the medical
      comorbidities that so often accompany it. Endovascular aneurysm repair (EVAR) is
      a landmark contribution to the management of such patients and has been
      associated with significant overall reductions in the operative mortality rate in
      statewide and national audits. This early advantage of EVAR comes at the price of
      a unique set of complications, secondary interventions, and related expenses,
      however, and randomized clinical trials of EVAR versus open repair have not yet
      demonstrated differences in survival or quality of life within 4 years of follow
      up. Data from the Nationwide Inpatient Sample and other sources indicate that the
      mortality rate for open AAA repair appears to be less than 2% in patients who are
      65 years of age or younger. This low operative risk may not justify exposure to
      whatever incidence of late complications the current generation of endografts may
      prove to have during the relatively long survival times that can be anticipated
      for these patients.

PMID- 17182935
TI  - Aortic aneurysm, thoracoabdominal aneurysm, juxtarenal aneurysm, fenestrated
      endografts, branched endografts, and endovascular aneurysm repair.
AB  - The development of endovascular devices to treat aneurysms that abut or involve
      the visceral vessels has occurred in an effort to reduce the significant
      procedural morbidity and mortality associated with conventional repair. To
      accomplish this, three systems have been trialed. The first technique was
      developed to treat juxtarenal aneurysms and involves the placement of customized
      fenestrations strategically placed within the fabric of the graft. These are
      aligned with the ostia of the visceral vessels incorporated by the repair and
      supplemented by the placement of a balloon expandable stent. In a similar
      fashion, aneurysms that involve the visceral vessels can be treated with a
      fenestrated graft where the fenestration is reinforced with a nitinol ring. This
      is then mated with a balloon-expandable stentgraft, allowing the devices to seal
      at the level of the nitinol ring. An alternative means of incorporating the
      visceral vessels is to use directional branches where one or more additional
      limbs (typically 8 mm) are anastomosed to the aortic graft, through which access
      into the visceral vessel is attained. Mating stentgrafts for the later design can
      be of a self-expanding or balloon expandable nature. The experience with
      fenestrated devices is mature and associated with a low perioperative mortality
      (<2%) without many long-term complications. The treatment of thoracoabdominal
      aneurysms with branches has provided us with optimism regarding the technique,
      but results are only short term in nature. Further device development is ongoing
      and dissemination of this technology is now occurring in Europe, Australia and
      Canada.

PMID- 17182936
TI  - Vibrometry: a novel noninvasive application of ultrasonographic physics to
      estimate wall stress in native aneurysms.
AB  - Our objective was to test vibrometry as a means to measure changes in aneurysm
      sac pressure in an in vitro aneurysm model. Explanted porcine abdominal aortas
      and nitrile rubber tubes were used to model an aneurysm sac. An ultrasound beam
      was used to vibrate the surface of the aneurysm model. The motion generated on
      the surface was detected either by reflected laser light or by a second
      ultrasound probe. This was recorded at different aneurysm pressures. The phase of
      the propagating wave was measured to assess changes in velocity and to see if
      there was a correlation with aneurysm pressure. The cumulative phase shift
      detected by laser or Doppler correlated well with increasing hydrostatic pressure
      in both the rubber and the porcine aorta model. The square of the mean pressure
      correlated well with the cumulative phase shift when dynamic pressure was
      generated by a pump. However, the pulse pressure was poorly correlated with the
      cumulative phase shift. Noninvasive measurement of changes in aortic aneurysm sac
      tension is feasible in an in vitro setting using the concept of vibrometry. This
      could potentially be used to noninvasively detect wall stress in native aneurysms
      and endotension after endovascular aneurysm repair (EVAR) and to predict the risk
      of rupture.

PMID- 17182937
TI  - Combining open and endovascular approaches to complex aneurysms.
AB  - Patients with aortic aneurysms commonly present with anatomic issues that
      preclude them from receiving purely endovascular repairs. In these situations,
      open surgical procedures can be used to manage anatomic problems and facilitate
      endovascular aneurysm repair. This report focuses on combined approaches that
      enable repair of abdominal or thoracoabdominal aortic aneurysms that involve the
      mesenteric and/or renal circulation. Current experience with combined
      open/endovascular repairs is essentially anecdotal. The common feature among the
      open procedures is establishment of extra-anatomic perfusion of the visceral
      arteries to enable ligation and subsequent coverage of their ostia during
      endograft placement. The existing reports are notable for the marked variability
      in many factors including extent of aneurysm repair, surgical approach, mode of
      visceral revascularization, conduit for bypass, and type of endovascular device
      used. Overall, current reports demonstrate that patients with limited physiologic
      reserve and complex aortic anatomy can be treated successfully by combining open
      and endovascular repairs. As endograft design and endovascular techniques
      continue to improve, combined approaches are likely to play an increasingly
      important role in the treatment of extensive aortic disease.

PMID- 17182938
TI  - Engineering improvements in endovascular devices: design and validation.
AB  - Advances in endovascular treatment of vascular disease have focused on basic and
      translational research of vascular disease and endovascular devices. Clinical
      trials serve to establish the safety and efficacy of engineering advances that
      incorporate this research. Recent position statements by the Food and Drug
      Administration (FDA) emphasize that research into conducting these trials in a
      timely and cost-effective manner (critical path research) is as important to
      patient care as the engineering advances themselves. This article reviews the
      recent FDA documents discussing critical path research, highlighting those topics
      that the FDA emphasizes. Several directions of translational research in which
      engineering advances may contribute to enhanced device design and improved
      patient care are reviewed.

PMID- 17182939
TI  - Abdominal aortic aneurysm is a specific antigen-driven T cell disease.
AB  - To determine whether monoclonal/oligoclonal T cells are present in abdominal
      aortic aneurysm (AAA) lesions, we amplified beta-chain T cell receptor (TCR)
      transcripts from these lesions by the nonpalindromic adaptor (NPA)-polymerase
      chain reaction (PCR)/V-beta-specific PCR followed by cloning and sequencing.
      Sequence analysis revealed the presence of substantial proportions of identical
      beta-chain TCR transcripts in AAA lesions in 9 of 10 patients examined, strongly
      suggesting the presence of oligoclonal populations of alphabeta TCR+ T cells. We
      have also shown the presence of oligoclonal populations of gammadelta TCR+ T
      cells in AAA lesions. Sequence analysis after appropriate PCR amplification and
      cloning revealed the presence of substantial proportions of identical VgammaI and
      VgammaII TCR transcripts in 15 of 15 patients examined, and of Vdelta1 and
      Vdelta2 TCR transcripts in 12 of 12 patients. These clonal expansions were very
      strong. All these clonal expansions were statistically significant by the
      binomial distribution. In other studies, we determined that mononuclear cells
      infiltrating AAA lesions express early- (CD69), intermediate- (CD25, CD38), and
      late- (CD45RO, HLA class II) activation antigens. These findings suggest that
      active ongoing inflammation is present in the aortic wall of patients with AAA.
      These results demonstrate that oligoclonal alphabeta TCR+ and gammadelta TCR+T
      cells are present in AAA lesions. These oligoclonal T cells have been clonally
      expanded in vivo in response to yet unidentified antigens. Although the antigenic
      specificity of these T cells remains to be determined, these T cells may play a
      significant role in the initiation and/or the propagation of the AAA. It appears
      that AAA is a specific antigen-driven T cell disease.

PMID- 17182940
TI  - Genes predisposing to rapid aneurysm growth.
AB  - The aim of the study was to investigate the effect of functional polymorphisms in
      promoters of the MMP-2 (-1306 C > T), MMP-3 (-1171 5A > 6A), MMP-9 (-1562 C > T),
      MMP-12 (-82 A > G), TIMP-1 (-372 C > T), and PAI-1 (-675 4G > 5G and -847 A > G)
      genes on the growth rate of small abdominal aortic aneurysms. The patients with
      small aneurysms were recruited from the surveillance arm of the U.K. Small
      Aneurysm Trial and monitored for aneurysm growth, mean follow-up 2.6 years. Mean
      linear aneurysm growth rates were calculated by flexible modeling. For MMP-2, MMP
      3, MMP-9, MMP-12, and TIMP-1 polymorphisms there were no clear associations with
      aneurysm growth. The increased growth rates for patients of 5G5G PAI-1 genotype
      were of borderline significance (P = 0.06). However, PAI-1 haplotype analysis
      showed that 5G5G/GG patients had significantly faster aneurysm growth (mean 0.46
      mm/year faster). There was no evidence that any specific MMP polymorphism had a
      clinically significant effect on aneurysm growth. However the plasminogen system
      (via PAI-1) appears to have a small, but clinically significant, role in aneurysm
      growth.

PMID- 17182941
TI  - Genetic basis of thoracic aortic aneurysms and dissections: potential relevance
      to abdominal aortic aneurysms.
AB  - Ascending thoracic aortic aneurysms leading to type A dissections (TAAD) have
      long been known to occur in association with a genetic syndrome such as Marfan
      syndrome (MFS). More recently, TAAD has also been demonstrated to occur as an
      autosomal dominant disorder in the absence of syndromic features, termed familial
      TAAD. Familial TAAD demonstrates genetic heterogeneity, and linkage studies have
      identified TAAD loci at 5q13-14 (TAAD1), 11q23 (FAA1), 3p24-25 (TAAD2), and
      16p12.2-13.13. The genetic heterogeneity of TAAD is reflected by variation in
      disease in terms of the age of onset, progression, penetrance, and association
      with additional cardiac and vascular features. The underlying genetic
      heterogeneity of TAAD is reflected in the phenotypic variation associated with
      familial TAAD with respect to age of onset, progression, penetrance, and
      association with additional cardiac and vascular features. Mutations in the
      TGFBR2 gene have been identified as the cause of disease linked to the 3p24-25
      locus, implicating dysregulation of TGF-beta signaling in TAAD. Mutations in
      myosin heavy chain (MYH11), a smooth muscle cell-specific contractile protein,
      have been identified in familial TAAD associated with patent ductus arteriosus
      (PDA) linked to 16p12.2-12.13. The identification of these novel disease pathways
      has led to new directions for future research addressing the pathology and
      treatment of TAAD.

PMID- 17182942
TI  - Structural and functional genetic disorders of the great vessels and outflow
      tracts.
AB  - Development of the aorta and pulmonary artery is a complex process involving
      multiple molecular genetic pathways that modulate morphogenesis of the outflow
      tracts and the anastomosis of branch vessels. Recent genetic studies of the
      cardiovascular system demonstrate that congenital and adult onset progressive
      disorders of the great vessels such as aneurysms are components of generalized
      vascular, cardiac, and extracardiovascular syndromes. Current paradigms suggest
      that aortic disease is founded in patterning anomalies of the conotruncus that
      occur in utero. These aberrations can be consequences of genetic aberrations in
      transcriptional regulation of signal transduction both within and outside the
      developing great vessels.

PMID- 17182943
TI  - Genome-wide approach to finding abdominal aortic aneurysm susceptibility genes in
      humans.
AB  - Familial aggregation of abdominal aortic aneurysms (AAAs) is now widely
      recognized, however, susceptibility genes have not yet been identified. Our
      approach to find susceptibility genes has been to collect families with AAAs and
      to perform DNA linkage analyses to identify regions on the human chromosomes that
      are linked to AAAs and could harbor susceptibility genes for AAAs. We identified
      233 families with at least two individuals diagnosed with AAAs. These families
      had 653 AAA patients and an average of 2.8 cases per family. When evaluating mode
      of inheritance, 167 (72%) families were consistent with autosomal recessive
      inheritance, whereas 58 (25%) families were consistent with autosomal dominant
      inheritance and in 8 families the familial aggregation could be explained by
      autosomal dominant inheritance with incomplete penetrance. Blood samples from 235
      affected relative pairs (ARPs) and their unaffected relatives were collected for
      DNA isolation and the DNA used for genotyping with highly variable microsatellite
      markers. We included covariates in the statistical analyses to allow for genetic
      heterogeneity. The results for chromosomes 19g13 and 4q31 were significant with
      sex, number of affected first-degree relatives, and their interaction as
      covariates. These chromosomal regions contain many plausible candidate genes, and
      the future research will include more detailed analyses of these positional
      candidate genes.

PMID- 17182944
TI  - The candidate gene approach to susceptibility for abdominal aortic aneurysm:
      TIMP1, HLA-DR-15, ferritin light chain, and collagen XI-Alpha-1.
AB  - There are two approaches to gene discovery for diseases when genetic
      susceptibility has been implicated by clinical genetic or case-control studies:
      (1) genome-wide screening and (2) evaluation of candidate genes. Each has
      specific advantages and disadvantages. The principal advantage of genome-wide
      screening is that it is impeccably objective in as much as it proceeds without
      any presuppositions regarding the importance of specific pathobiological features
      of the disease process. The principal disadvantage is that such a study is
      expensive and resource intensive. A large population of enrolled patients and
      multidisciplinary teams of investigators cooperating from several institutions
      are usually required. The alternative approach of evaluating candidate genes can
      be pursued by a small independent laboratory with limited funding and resources,
      a small collection of clinical specimens, and a small number of team players. The
      disadvantage is that it is by necessity highly subjective in the process of
      selecting specific candidates among many reasonable possibilities. There is no a
      priori assurance that effort will not be expended on one or more candidates that
      turn out in the end to be failures. This report reviews efforts in our laboratory
      to evaluate four genes as candidates. One of these tissue inhibitor of
      metalloprotease 1(TIMP1) led to the description of a polymorphism, but not a
      conclusive mutation. The other three (HLA-DR-15, ferritin light chain (FTL), and
      collagen XI-alpha-1 (COL11A1) are subjects of continuing interest.

PMID- 17182945
TI  - Aneurysm Outreach Inc., a nonprofit organization, offers community-based,
      ultrasonography screening for abdominal aortic aneurysms.
AB  - Aneurysm Outreach Inc. (AOI; http://www.alink.org) is a nonprofit volunteer
      organization founded in 1999 whose aim is to (a) raise public awareness about
      aneurysms; (b) stimulate and fund genetic research through donations; and (c)
      coordinate a support network for aneurysm patients and their families. Since
      abdominal ultrasonography examination of an asymptomatic individual is not
      presently reimbursed by health insurance in the United States, one of the
      initiatives supported by AOI is to have free ultrasonography screening for
      abdominal aortic aneurysm (AAA) for those most at risk. One of the initiatives
      supported by AOI is to have free ultrasonography screening for abdominal aortic
      aneurysm (AAA). To meet this goal, a free screening program was initiated in
      September 2001 and by November 2004 approximately 3,000 participants were
      screened and 61 (2.0%) participants were confirmed to have a dilated aorta and
      were referred to their primary care physicians or vascular surgeons for further
      follow-up and treatment, if indicated.

PMID- 17182946
TI  - Diffusion of Alexa Fluor 488-conjugated dendrimers in rat aortic tissue.
AB  - In this study, the distribution of labeled dendrimers in native and aneurysmal
      rat aortic tissue was examined. Adult male rats underwent infrarenal aorta
      perfusion with generation 5 (G5) acetylated Alexa Fluor 488-conjugated dendrimers
      for varying lengths of time. In a second set of experiments, rats underwent
      aortic elastase perfusion followed by aortic dendrimer perfusion 7 days later.
      Aortic diameters were measured prior to and postelastase perfusion, and again on
      the day of harvest. Aortas were harvested 0, 12, or 24 h postperfusion, fixed,
      and mounted. Native aortas were harvested and viewed as negative controls. Aortic
      cross-sections were viewed and imaged using confocal microscopy. Dendrimers were
      quantified (counts/high-powered field). Results were evaluated by repeated
      measures ANOVA and Student's t-test. We found that in native aortas, dendrimers
      penetrated the aortic wall in all groups. For all perfusion times, fewer
      dendrimers were present as time between dendrimer perfusion and aortic harvest
      increased. Longer perfusion times resulted in increased diffusion of dendrimers
      throughout the aortic wall. By 24 h, the majority of the dendrimers were through
      the wall. Dendrimers in aneurysmal aortas, on day 0 postdendrimer perfusion,
      diffused farther into the aortic wall than controls. In conclusion, this study
      documents labeled dendrimers delivered intra-arterially to native rat aortas in
      vivo, and the temporal diffusion of these molecules within the aortic wall.
      Increasing perfusion time and length of time prior to harvest resulted in
      continued dendrimer diffusion into the aortic wall. These preliminary data
      provide a novel mechanism whereby local inhibitory therapy may be delivered
      locally to aortic tissue.

PMID- 17182947
TI  - Hypoxia at the site of abdominal aortic aneurysm rupture is not associated with
      increased lactate.
AB  - The mechanisms of hypoxia-mediated aneurysm wall weakening and rupture are
      unknown. During hypoxia, strategies to maintain cellular ATP levels include
      increasing glycolysis (glycolytic strategy) or decreasing ATP consumption
      (metabolic depression). This study demonstrated that compared to anterior
      aneurysm sac, rupture edge overexpressed hypoxia-inducible factor-1-alpha (marker
      of hypoxia) and showed no significant difference in levels of combined ADP and
      ATP or lactate (glycolytic end product). Further studies are needed to confirm
      whether hypoxic AAA cells adapt through metabolic depression rather than
      glycolysis. The downregulation of protein synthesis during such metabolic
      depression may be a factor in hypoxia-mediated wall weakening.

PMID- 17182948
TI  - Gene expression profile of abdominal aortic aneurysm rupture.
AB  - To search for novel transcriptional pathways that are activated in abdominal
      aortic aneurysm rupture, cDNA microarrays were used to compare global mRNA
      expression at the aneurysm rupture edge to anterior sac, and selected results
      were confirmed using quantitative real-time-polymerase chain reaction (QRT-PCR).
      This study identified apoptosis, angiogenesis, and inflammation as potentially
      important participants during the process of aneurysm rupture.

PMID- 17182949
TI  - Increased angiogenesis at the site of abdominal aortic aneurysm rupture.
AB  - Abdominal aortic aneurysm (AAA) rupture is associated with elevated levels of
      matrix metalloproteinase (MMP). Medial neovascularization is a known
      characteristic of established AAAs and involves proteolytic degradation of
      extracellular matrix by MMPs to facilitate endothelial cell proliferation and
      migration. This study evaluated the extent of neovascularization in abdominal
      aortic aneurysm rupture. Results indicated upregulation of proangiogenic
      cytokines and increased medial neovascularization at the aneurysm rupture edge
      compared with paired aneurysm anterior sac. Further investigations into the role
      of angiogenesis in aneurysm rupture may open novel therapeutic avenues to prevent
      aneurysm rupture.

PMID- 17182950
TI  - Aortic aneurysms as a source of circulating interleukin-6.
AB  - In keeping with the inflammatory paradigm of abdominal aortic aneurysm (AAA)
      pathophysiology, in vitro studies suggest that aneurysms secrete the
      proinflammatory cytokine interleukin-6 (IL-6). Circulating IL-6 levels are higher
      in patients with AAA with elevated circulating IL-6 an independent risk factor
      for cardiovascular mortality. To investigate whether aneurysms secrete IL-6 into
      the circulation, arterial IL-6 was measured from within the aorta in three groups
      of patients undergoing endovascular procedures; 27 AAA, 10 thoracic aneurysms
      (TA), and 15 controls. Overall, IL-6 was higher in the aneurysm groups (P <
      0.0008) with significant rises corresponding to positions downstream to the
      aneurysm in both AAA and TA. There were no significant differences in IL-6 with
      aortic position in the control group. These data support the hypothesis that
      aneurysms secrete IL-6 into the circulation and may account for the high
      cardiovascular mortality observed in patients with aneurysms.

PMID- 17182951
TI  - Circulating cytokines in patients with abdominal aortic aneurysms.
AB  - Studies suggest that aneurysm-derived cytokines perpetuate the cycle of
      inflammation and proteolysis that is the pathological hallmark of abdominal
      aortic aneurysms (AAA). As interleukin (IL)-6 is an independent risk factor for
      cardiovascular mortality, such cytokines may also have important systemic
      effects. The purpose of this study was to investigate the effect of aneurysm
      repair on circulating levels of cytokines. Inflammatory cytokines were measured
      in 99 patients with AAA and 100 patients who had undergone AAA repair in the
      past. There was a significant reduction in IL-10 in the postoperative group, and
      a nonsignificant trend toward reduction in IL-6 and CRP in the postoperative
      group. Subgroup analysis of the postoperative group revealed significantly lower
      levels of IL-6 and CRP in the open group compared to endovascular aneurysm repair
      (EVAR). These results suggest that aneurysm repair may have an effect upon
      chronic levels of circulating inflammatory cytokines, and that the type of repair
      may exert some influence.

PMID- 17182952
TI  - Endothelial progenitor cells and abdominal aortic aneurysms.
AB  - Endothelial progenitor cells (EPCs) are a population of circulating stem cells
      that hone in to sites of vascular injury where they undergo differentiation to
      become incorporated into damaged tissue. The aim of this study was to enumerate
      EPCs in patients with abdominal aortic aneurysms (AAA). CD133(+) peripheral blood
      mononuclear cells were immunomagnetically selected and CD34/CD133 was used as a
      marker of EPCs. EPCs were detected using flow cytometry. AAA patients had
      significantly higher levels of circulating EPCs than age-matched controls (2.43%
      vs. 1.25% of all events, P = 0.008). The role and function of EPCs in AAA remain
      to be determined, but their implication with angiogenesis may represent one
      plausible mechanism.

PMID- 17182953
TI  - Increasing evidence for immune-mediated processes and new therapeutic approaches
      in abdominal aortic aneurysms--a review.
AB  - Animal models for abdominal aortic aneurysms (AAAs), immunogenetical and
      pathophysiological studies support the importance of immune-mediated processes in
      the pathogenesis of AAA disease. Neutrophils, natural killer (NK) cells,
      monocytes/macrophages, and proinflammatory cytokines are involved in the complex
      and dynamic tissue remodeling of the AAA vessel wall. Our group showed an
      increased prevalence of circulating interferon-gamma (IFN-gamma) producing CD28(
      ) T cells especially in smaller AAAs, thus supporting the concept of a T cell
      mediated pathophysiology of AAAs, especially during the early development of
      AAAs. Further research should now assess the possible benefit of anti
      inflammatory therapeutic approaches in AAA patients, especially with small AAAs.

PMID- 17182954
TI  - Pathogenesis of thoracic and abdominal aortic aneurysms.
AB  - The major disease processes affecting the aorta are aortic aneurysms and
      dissections. Aneurysms are usually described in terms of their anatomic location,
      with thoracic aortic aneurysms (TAAs) involving the ascending and descending
      aorta in the thoracic cavity and abdominal aortic aneurysms (AAAs) involving the
      infrarenal abdominal aorta. Both thoracic and abdominal aortas are elastic
      arteries, and share similarities in their physical structures and cellular
      components. However, thoracic and abdominal aortas differ in their biochemical
      properties and the origin of their vascular smooth muscle cells (VSMCs). These
      similarities and differences between thoracic and abdominal aortas provide the
      basis for the various pathologic mechanisms observed in this disease. This review
      focuses on the comparison of the pathologic mechanisms involved in TAA and AAA.

PMID- 17182955
TI  - Attenuation of experimental aortic aneurysm formation in P-selectin knockout
      mice.
AB  - The aim of this study was to determine the role of P-selectin, an adhesion
      molecule found on the surface of activated platelets and endothelial cells during
      experimental aortic aneurysm formation. Infrarenal abdominal aortas of C57 black
      wild-type (WT) mice and P-selectin knockout (PKO) mice were measured in situ and
      then perfused with porcine pancreatic elastase (0.332 U/mL). Whole blood was
      drawn from the tail artery on day 2 pre-perfusion to determine total and
      differential white blood cell (WBC) counts. On day 14 postperfusion, aortic
      diameters (AD) of WT mice (N = 19) and PKO mice (N = 9) were measured. An aortic
      aneurysm was defined as a 100% or greater increase in AD from pre-perfusion
      measurement. Immunohistochemistry, including H&E, trichrome and von Gieson
      staining, was performed on harvested aortic tissue. Statistical analysis was
      performed by t-test and Fisher's exact test. There were no significant
      differences in peripheral leukocyte counts at baseline between the two groups. WT
      mice had significantly larger AD compared to PKO mice at day 14 postperfusion
      (116 % vs. 38 %, P < 0.001). Aortic aneurysm penetrance was 52% in WT mice, while
      0% (P = 0.01) of PKO mice formed aneurysms. On histologic examination, WT mouse
      aortas were associated with a significant inflammatory response and degradation
      of elastin and collagen fibers, while PKO mouse aortas lacked signs of
      inflammation or vessel wall injury. P-selectin deficiency attenuates aneurysm
      formation in the elastase aortic perfusion model. This was associated with a
      blunting of the inflammatory response and preserved vessel wall intergrity
      following elastase perfusion in the P-selectin knockout mice. Further
      investigation to elucidate the independent contributions of endothelial cell and
      platelet P-selectin in experimental aortic aneurysm formation is required.

PMID- 17182956
TI  - Global expression profiles in human normal and aneurysmal abdominal aorta based
      on two distinct whole genome microarray platforms.
AB  - Abdominal aortic aneurysms (AAA) are the thirteenth cause of death in the United
      States. The etiology of the disease is yet largely unknown, although several
      environmental risk factors (e.g., smoking) have been identified and the search
      for finding genetic risk factors has been initiated. The purpose of our study was
      to gain insight into the pathobiology of AAA by determining which genes are
      expressed in the abdominal aorta under either the diseased or normal states,
      thereby generating the whole-genome-wide expression profiles for these
      conditions.

PMID- 17182957
TI  - Thoracic aortic compliance as a determinant of rupture of abdominal aortic
      aneurysms.
AB  - The relative importance of collagen and elastin in formation, expansion, and
      rupture of abdominal aortic aneurysms (AAAs) has been investigated extensively.
      Aortic compliance, which is a relevant component of cardiac afterload, is also
      determined by the relative amount of media proteins in large arteries as well as
      by pathological arterial processes. The objective of this study was to determine
      if thoracic aortic compliance was different in patients with ruptured AAAs
      compared to those undergoing elective AAA repair. The study was carried out in 43
      patients with infrarenal AAAs in the postoperative period. The first group (A)
      included 17 patients undergoing emergency ruptured AAA repair. The second group
      (B) included 26 patients operated on for an AAA who underwent elective repair.
      Patients were studied by a noninvasive Doppler echocardiography. Pulse wave
      velocity (PWV) was determined in the descending thoracic aorta. Results show that
      patients with electively repaired AAAs had an accelerated pulse wave
      transmission, typical of an atherosclerotic aorta with a Gaussian distribution
      (PWV 9.26 m/sec +/- 1.27). In contrast, patients with ruptured aneurysms
      presented in a distribution with three peaks. A striking increase in aortic
      compliance (41% of patients with PWV<6 m/sec in group A vs. 3% of group B) was
      observed in patients with ruptured AAAs.

PMID- 17182958
TI  - Female gender attenuates cytokine and chemokine expression and leukocyte
      recruitment in experimental rodent abdominal aortic aneurysms.
AB  - Female gender appears to be protective in the development of abdominal aortic
      aneurysms (AAAs). This study sought to identify gender differences in cytokine
      and chemokine expression in an experimental rodent AAA model. Male and female
      rodent aortas were perfused with either saline (control) or elastase to induce
      AAA formation. Aortic diameter was determined and aortic tissue was harvested on
      postperfusion days 4 and 7. Cytokine and chemokine gene expression was examined
      using focused gene arrays. Immunohistochemistry was used to quantify aortic
      leukocyte infiltration. Data were analyzed by Student's t-tests and ANOVA.
      Elastase-perfused female rodents developed significantly smaller aneurysms
      compared to males by day 7 (93 +/- 10% vs. 201 +/- 25%, P = 0.003). Elastase
      perfused female aortas exhibited a fivefold decrease in expression of the BMP
      family and ligands of the TNF superfamily compared to males. In addition, the
      expression of members of the TGF beta and VEGF families were three to fourfold
      lower in female elastase-perfused aortas compared to males. Multiple members of
      the interleukin, CC chemokine receptor, and CC ligand families were detectable in
      only the male elastase-perfused aortas. Female elastase-perfused aortas
      demonstrated a corollary twofold lower neutrophil count (females: 17.5 +/- 1.1
      PMN/HPF; males: 41 +/- 5.2 neutrophils/HPF, P = 0.01) and a 1.5-fold lower
      macrophage count (females: 12 +/- 1.1 macrophages/HPF; males: 17.5 +/- 1.1
      macrophages/HPF, P = 0.003) compared to male elastase-perfused aortas. This study
      documents decreased expression of multiple cytokines and chemokines and
      diminished leukocyte trafficking in female rat aortas compared to male aortas
      following elastase perfusion. These genes may contribute to the gender disparity
      seen in AAA formation.

PMID- 17182959
TI  - Features and genomic origins of matrix cell adhesion molecules-1 and -2 expressed
      by fibroblasts of human aortic adventitial origin.
AB  - Precursor mRNAs for proteins that we have called matrix cell adhesion molecules-1
      and -2 (Mat-CAM-1 and Mat-CAM-2) were cloned from fibroblasts cultured from a
      specimen of human abdominal aorta. Both protein sequences have the unusual
      feature that there is an immunoglobulin kappa (Igkappa)-like domain at the N
      terminus and they are glycine/proline rich in the C-terminal domain. Antibodies
      were raised in rabbit against peptides synthesized for a specific unique sequence
      of Mat-CAM-1 and Mat-CAM-2, respectively (not detected in any other proteins
      referenced in GenBank). Both antibodies were immunoreactive with adventitial
      microfibrils of the aorta and some additional arteries. Mat-CAM-1 was detected in
      the common/internal iliac arteries, but it was not detected in the external iliac
      artery. Conversely, Mat-CAM-2 was conspicuous in the external iliac artery, but
      not the common/internal iliac arteries. Thus, these proteins show features of
      site-specific expression within the arterial tree. Computerized searches show
      that the genomic origins of Mat-CAM-1 and -2 are in the so-called
      nasopharnygocarcinoma (NPC) gene on chromosome 2, which is a putative oncogene.
      Expression of the two different gene products from the same genomic sequence
      requires shifts of reading frame. Further studies will be required to determine
      whether these proteins are prototypes for a larger family of tissue-specific
      matrix proteins arising from alternative transcriptions of the same genomic
      sequence.

PMID- 17182960
TI  - Arterial aneurysms in HIV patients: molecular mimicry versus direct infection?
AB  - There is growing literature on the subject of aneurysmal degeneration of arteries
      in patients who are infected with HIV. A patient recently seen at our medical
      center with an aneurysm of the carotid artery stimulated our interest in
      reviewing the mechanisms by which HIV may initiate or predispose to these
      pathologies. There are at least three major possibilities: (1) immunodeficiency
      allows bacteria that are known to cause mycotic aneurysms to proliferate without
      immune restraint; (2) one or more of the HIV envelope proteins sufficiently
      resemble one or more artery-specific-antigenic proteins (ASAPs) that may trigger
      an autoimmune response (molecular mimicry); and (3) the HIV virus itself infects
      arterial-resident cells that maintain the integrity of the load-bearing matrix.
      The computational searches reported here suggest that the ASAP, matrix cell
      adhesion molecule-1 (Mat-CAM-1), has a high degree of similarity to known ligands
      for HIV envelope proteins gp41 and gp120. No similarities of Mat-CAM-1 to the HIV
      envelope glycoproteins were detected. Accordingly, among the possibilities for
      explaining the HIV/aneurysm connection, direct infection of aortic fibroblasts by
      the HIV virus is more likely to be the pathogenetic mechanism than the process of
      molecular mimicry.

PMID- 17182961
TI  - HLA-DQA is associated with abdominal aortic aneurysms in the Belgian population.
AB  - Chronic inflammation and autoimmunity likely contribute to the pathogenesis of
      abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the
      role of autoimmunity in the etiology of AAAs using a genetic association study
      approach with human leukocyte antigen (HLA) polymorphisms (HLA-DQA1, -DQB1, -DRB1
      and -DRB3-5 alleles) in 387 AAA cases and 426 controls. We observed an
      association with the HLA-DQA1 locus among Belgian males, and found a significant
      difference in the HLA-DQA1*0102 allele frequencies between AAA cases and
      controls. In conclusion, this study showed potential evidence that the HLA-DQA1
      locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a
      role in the pathogenesis of AAAs.

PMID- 17182962
TI  - Toward a model for local drug delivery in abdominal aortic aneurysms.
AB  - The formation of an abdominal aortic aneurysm (AAA) may eventually result in
      rupture, an event associated with a 50% mortality rate. This work represents a
      first step toward improving current stress estimation techniques and local
      transport simulations in AAA. Toward this aim, a computational parametric study
      was performed on an axisymmetric cylindrical FEM of a 5 cm AAA with a 1.5 cm
      thick intraluminal thrombus (ILT). Both the AAA wall and ILT were modeled as
      porohyperelastic PHE materials using estimated values of AAA wall and ILT
      permeability. While no values for AAA wall permeability could be found in the
      literature, the value of ILT permeability was taken from a previous investigation
      by Adolph et al.(7) Peak stresses, fluid velocities, and local pore pressure
      values within the ILT and wall were recorded and analyzed as a function of the
      cardiac cycle. While peak wall stress values for the PHE models did not largely
      differ from corresponding solid finite element simulations (186.2 N/cm(2) vs.
      186.5 N/cm(2)), the stress in the abluminal region of the ILT increased by 17.4%
      (7.7 N/cm(2) vs. 6.5 N/cm(2)). Pore pressure values were relatively constant
      through the ILT while there were significant pore pressure gradients present in
      the AAA wall. The magnitude of fluid velocities varied in magnitude and direction
      throughout the cardiac cycle with large fluctuations occurring on the luminal
      surface. The combination of the patient-specific PHE AAA FEMs with mass transport
      simulations will result in spatially and time-varying concentration distributions
      within AAA, which may benefit future pharmaceutical treatments of AAA.

PMID- 17182963
TI  - Gender-related differences in the tensile strength of abdominal aortic aneurysm.
AB  - A recent study investigated the association of gender with the growth rate of
      AAAs and found a significant increase in the growth rate of AAAs in women than in
      men. On the basis of these observations, we hypothesize that there are gender
      associated differences in AAA wall integrity and mechanical strength. The purpose
      of this study was to explore this hypothesis by comparing the tensile strength of
      freshly resected AAA tissue specimens between women and men. Seventy-six
      rectangular specimens (20 mm long x 5 mm wide) from 34 patients (24 male, 10
      female) were excised from the anterior wall of patients undergoing open repair of
      their abdominal aortic aneurysm and tested in a uniaxial tensile tester. Ultimate
      tensile strength (UTS) was taken as the peak stress obtained before specimen
      failure. While there were no statistical differences in strength between
      specimens taken from male and female patients, there was a trend toward a
      decrease in strength in females as compared to males (87.6 +/- 6.7 N/cm(2) vs.
      67.6 +/- 8.1 N/cm(2), p = 0.09). To the authors knowledge this work represents
      the first report of differences in biomechanical properties as a function of
      gender. The nearly significant decrease in UTS in women versus men reported here
      may be important in assessing the risk of rupture in AAA. Further testing is
      warranted to confirm the current trends.

PMID- 17182964
TI  - Identification of c-Jun N-terminal kinase as a therapeutic target for abdominal
      aortic aneurysm.
AB  - Despite the advances in molecular cell biology, identification of a therapeutic
      target in a given disease still poses a significant challenge. Here we report a
      strategy for identification of the therapeutic target in abdominal aortic
      aneurysm (AAA). We screened for various signaling molecules in human AAA samples
      and identified c-Jun N-terminal kinase (JNK) as a prominently activated molecule.
      The JNK pathway-oriented transcriptome analyses revealed that activation of JNK
      leads to enhancement of the activity of matrix metalloproteinases and,
      concurrently, suppression of the extracellular matrix biosynthesis, suggesting
      that JNK may represent a novel therapeutic target in AAA.

PMID- 17182965
TI  - The abdominal aortic aneurysm. Genetics, pathophysiology, and molecular biology.
      Proceedings of a conference. April 3-5, 2006. New York, New York, USA.

PMID- 17182966
TI  - Lipophilic statins suppress cytotoxicity by freshly isolated natural killer cells
      through modulation of granule exocytosis.
AB  - NK cells, a component of the innate immune system, provide a first line of
      defense against viral infections and malignancies, interact with the adaptive
      immune system and have a role in rejection of allogeneic bone marrow transplants
      and solid allo- and xenotransplants. Immunoregulatory activity by the anti
      hypercholesterolemia agents, 3-hydroxy-3-methyl-glutaryl Coenzyme A (HMG-CoA)
      reductase inhibitors, known as statins, has recently been reported. We analyzed
      the effects of three statins on human NK cell cytotoxicity. Two lipophilic
      statins (simvastatin and fluvastatin) suppressed the cytotoxic activity of fresh
      and IL-2-stimulated NK cells, while pravastatin, a hydrophilic statin, did not.
      Suppression was not associated with changes in intracellular perforin, granzyme A
      or granzyme B levels, or with changes in expression of leukocyte function
      associated antigen-1, an integrin known to regulate NK activity and reported to
      be altered by statin treatment. Decreased cytotoxicity was associated with
      decreased CD107a surface expression, indicating that the exocytosis pathway was
      compromised by simvastatin and fluvastatin but not by pravastatin. Mevalonate,
      the immediate downstream product of HMG-CoA reductase, partially reversed the
      effect of lipophilic statins on cytotoxicity and CD107a expression. Lipophilic
      statins also suppressed the release of the granule component, granzyme B, by IL-2
      activated NK cells following stimulation with K562. That lipophilic statins
      suppress NK cell activity through inhibition of the exocytosis pathway suggest an
      additional potential role for statins in inhibition of transplantation responses.

PMID- 17182967
TI  - Cooperation between MASP-1 and MASP-2 in the generation of C3 convertase through
      the MBL pathway.
AB  - The complement system is an important part of the innate immune system. Three
      pathways, the classical, the alternative and the lectin pathway, lead to the
      cleavage of complement factor C3, a central event in the activation of the
      complement system. We investigated the deposition of C3b (solid-phase C3
      activation product) on a mannan-coated surface at high concentration of human
      serum (17%). At these conditions, mannan-binding lectin (MBL) promoted the
      activation of C3 through the combined action of MBL-associated serine protease
      (MASP)-1 and MASP-2 without appreciable involvement of the alternative pathway.
      In serum depleted of MASP-1, MASP-2 and MASP-3, we observed synergetic effect of
      reconstitution with MASP-1 and MASP-2. This was inhibited by MASP-3. No C3b
      deposition was observed with C2- or C4-depleted serum. Depletion of factor B had
      no effect on the MBL-MASP-promoted C3b deposition. Our results demonstrate a
      function of the orphan protease MASP-1 by providing evidence that this enzyme
      collaborates with MASP-2 in the generation of C3 convertase, a process observable
      at high serum concentration, but not at low serum concentration.

PMID- 17182968
TI  - Association of CD4+CD25+Foxp3+ regulatory T cells with chronic activity and viral
      clearance in patients with hepatitis B.
AB  - Chronic activity of hepatitis B is thought to involve aberrant immune tolerance
      of unknown mechanism. In this study, we examined the role of
      CD4(+)CD25(+)Foxp3(+) regulatory T cells in disease activity and viral clearance
      in hepatitis B. Patients with chronic active hepatitis B (CAH) and asymptomatic
      HBV carriers (AsC) exhibited a significantly high frequency of
      CD4(+)CD25(+)Foxp3(+) T cells as opposed to that of controls and resolved HBV
      infection. These CD4(+)CD25(+) T cells expressed an elevated level of Foxp3 and
      displayed increased inhibitory activity towards both CD4(+)CD25(-) and CD8(+)
      effector cells. They were found to accumulate in liver biopsy tissue of CAH
      patients as opposed to controls. The frequency of CD4(+)CD25(+)Foxp3(+) T cells
      correlated positively with hepatitis B envelope (HBe) antigen status and serum
      HBV DNA copy numbers and had a converse relationship with HBe antibody status in
      patients with CAH and AsC. It was evident that in these patients, the increased
      frequency of CD4(+)CD25(+)Foxp3(+) T cells was associated with serum levels of
      transforming growth factor-beta known to promote peripheral conversion of
      CD4(+)CD25(-) T cells to CD4(+)CD25(+)Foxp3(+) regulatory T cells. The findings
      provide new insights into the role of CD4(+)CD25(+)Foxp3(+) regulatory T cells in
      chronic activity and viral clearance in chronic hepatitis B.

PMID- 17182969
TI  - Increased cortical expression of two synaptogenic thrombospondins in human brain
      evolution.
AB  - Thrombospondins are extracellular-matrix glycoproteins implicated in the control
      of synaptogenesis and neurite growth. Previous microarray studies suggested that
      one gene of this family, thrombospondin 4 (THBS4), was upregulated during human
      brain evolution. Using independent techniques to examine thrombospondin
      expression patterns in adult brain samples, we report approximately 6-fold and
      approximately 2-fold greater expression of THBS4 and THBS2 messenger RNA (mRNA),
      respectively, in human cerebral cortex compared with chimpanzees and macaques,
      with corresponding differences in protein levels. In humans and chimpanzees,
      thrombospondin expression differences were observed in the forebrain (cortex and
      caudate), whereas the cerebellum and most nonbrain tissues exhibited similar
      levels of the 2 mRNAs. Histological examination revealed THBS4 mRNA and protein
      expression in numerous pyramidal and glial cells in the 3 species but humans also
      exhibited very prominent immunostaining of the synapse-rich cortical neuropil. In
      humans, additionally, THBS4 antibodies labeled beta-amyloid containing plaques in
      Alzheimer's cases and some control cases. This is the first detailed
      characterization of gene-expression changes in human evolution that involve
      specific brain regions, including portions of cerebral cortex. Increased
      expression of thrombospondins in human brain evolution could result in changes in
      synaptic organization and plasticity, and contribute to the distinctive cognitive
      abilities of humans, as well as to our unique vulnerability to neurodegenerative
      disease.

PMID- 17182970
TI  - The challenge of embracing a smoke-free lifestyle: a neglected area in smoking
      cessation programs.
AB  - Relapse prevention theory and practice has focussed on teaching coping skills to
      deal with withdrawal and temptations to relapse with the result that treatments
      appear to be effective in reducing relapse over the short term, but not over the
      longer term. Once cravings subside ex-smokers face a further task of adjusting to
      a smoke-free lifestyle that involves learning to think and act like a non-smoker.
      To highlight this task, we operationalized a new conceptual framework that
      describes three tasks of quitting (the 3Ts): (i) making a quit attempt; (ii)
      learning to effectively deal with cravings and withdrawal; and (iii) adapting to
      a smoke-free lifestyle. This was introduced to the Quitline service in Victoria,
      Australia, in preparation for a randomized controlled trial aimed at testing
      whether a program of four to six extra callbacks could help ex-smokers with the
      third task and as a result reduce rates of relapse compared with Quitline's
      standard callback program. This paper describes the conceptual framework
      (focussing on the third task) and initial reactions to it from both Quitline
      advisors and callers. The conceptual framework is now integrated in the service
      and appears to have changed the way Quitline operates and the apparent
      expectations of its clients.

PMID- 17182971
TI  - A path model of smoking cessation in women smokers of low socio-economic status.
AB  - The goals of this study were to (i) determine how factors commonly implicated in
      smoking cessation processes influenced smoking cessation in low socio-economic
      status (SES) women and (ii) elucidate the pathways through which these factors
      may lead to quitting smoking. Secondary analysis was conducted on data from 644
      women smokers aged 18-45 years who had participated in an earlier experimental
      evaluation of a smoking cessation program, were still smokers at the 2-month post
      intervention survey and completed an interview 6 months later. Path analysis
      (LISREL 8) was used to test a conceptual model in which (i) factors considered as
      precursors to quitting (motivation, self-efficacy, confidence, action and
      intention to quit) directly predicted subsequent quitting and (ii) health
      concerns, social pressure to quit and daily stress influenced quitting indirectly
      through their effects on the precursor factors and (iii) mediated the effects of
      background characteristics (race, education, single motherhood, pregnancy and
      exposure to the earlier smoking cessation intervention) on quitting. Overall,
      results supported this conceptual model and its applicability to low-SES women
      smokers and indicated significant pathways among specific factors. In particular,
      (i) only plans to quit, confidence and social pressure to quit directly predicted
      quitting; (ii) both health concerns and social pressure increased motivation to
      quit and (iii) the negative effect of daily stress on quitting was mediated
      through decreased self-efficacy.

PMID- 17182972
TI  - Expanding our conceptualization of program implementation: lessons from the
      genealogy of a school-based nutrition program.
AB  - This work presents a theoretical framework in which health promotion and health
      education program implementation can be conceived as an open dynamic system. By
      tracing the evolution of an elementary school-based nutrition program from its
      conception to its recent form, we construct a program genealogy. Data were
      derived from two interviews and three historical documents from which historical
      events were identified and reconstructed in the form of a tree analogy. Data
      analysis ensued using concepts from the actor-network theory about social
      innovation. These concepts identified social and technical program attributes and
      situated them within a process which evolved over time, thus permitting the
      program's genealogy to appear. The genealogy was found to be influenced by the
      ways in which the involved actors interpreted the issue of food security, namely,
      as a professional issue, with a nutrition education response and as a social
      issue, with a community-building response. The interaction between the interests
      of the actors and the technical components of the program resulted in three
      temporal program iterations. The results highlight the important role played by
      the involved actors during program implementation and suggest the need to take
      these interests into consideration during all phases of program planning.

PMID- 17182973
TI  - Factors influencing participation rates and employees' attitudes toward promoting
      healthy eating at blue-collar worksites.

PMID- 17182974
TI  - Small-cell carcinoma of the penile urethra: a case report and a short review of
      the literature.

PMID- 17182975
TI  - Outcomes and predictors of chronic daily headache in adolescents: a 2-year
      longitudinal study.
AB  - OBJECTIVES: To assess the outcomes and predictors of chronic daily headache (CDH)
      in a community-based cohort of adolescents. METHODS: We established a field
      sample of 122 adolescents (32 M/90 F, ages 12 to 14) with CDH in 2000. These
      adolescents received annual follow-up by neurologists for 2 years via a
      semistructured telephone interview. CDH was defined as > or =15 headache
      days/month, average > or =2 h/day for >3 months; subtypes were classified based
      on the original and appendix criteria of the International Classification of
      Headache Disorders (2nd ed.; ICHD-2). Poor outcome was defined as persistence of
      CDH at 2 years. RESULTS: Follow-up response rates were 92% in 2001 and 84% in
      2002. Average monthly headache frequency was 11.0 +/- 9.7 days in 2001 and 7.7 +/
      6.5 days in 2002. CDH persistence rates were 40% in 2001 and 25% in 2002.
      Medication overuse declined from 20% (baseline) to 6% at 2 years. The prevalence
      of migraine did not change throughout the follow-up (67 to 60%), whereas that of
      tension-type headache deceased from 86 to 46% (p < 0.001). Chronic migraine
      prevalence increased markedly at baseline and became the most common CDH subtype
      at follow-up when using the ICHD-2 appendix criteria. During follow-up, seven
      subjects (6%) dropped out of school. Independent predictors for CDH persistence
      were medication overuse and major depression. CONCLUSIONS: Most adolescents with
      chronic daily headache (CDH) continued to have frequent headaches, although the
      incidence of CDH declined at follow-up. Migraine diagnosis gained prominence as
      headache frequency decreased. The percentages of chronic migraine in adolescents
      with CDH increased obviously if the appendix criteria were applied.

PMID- 17182976
TI  - Cholesterol level and symptomatic hemorrhagic transformation after ischemic
      stroke thrombolysis.
AB  - BACKGROUND: Prestroke statin use may improve ischemic stroke outcomes, yet there
      is also evidence that statins and extremely low cholesterol levels may increase
      the risk of intracranial hemorrhage. We evaluated the independent effect of
      statin use and admission cholesterol level on risk of symptomatic hemorrhagic
      transformation (sHT) after recanalization therapy for acute ischemic stroke.
      METHODS: We analyzed ischemic stroke patients recorded in a prospectively
      maintained registry that received recanalization therapies (IV or intra-arterial
      fibrinolysis or endovascular embolectomy) at a university medical center from
      September 2002 to May 2006. The independent effect of premorbid statin use on sHT
      post intervention was evaluated by logistic regression, adjusting for prognostic
      and treatment variables known to predict increased HT risk after ischemic stroke.
      RESULTS: Among 104 patients, mean age was 70 years, and 49% were men. Male sex,
      hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL)
      cholesterol, current smoking, elevated glucose levels, and higher admission NIH
      Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in
      univariate analysis. After adjusting for covariates, low LDL cholesterol (odds
      ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking
      (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1
      point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT
      risk. CONCLUSIONS: Lower admission low-density lipoprotein cholesterol level with
      or without statin use, current smoking, and greater stroke severity are
      associated with greater risk for symptomatic hemorrhagic transformation after
      recanalization therapy for ischemic stroke.

PMID- 17182977
TI  - Bradykinin B(2) receptor does not contribute to blood pressure lowering during
      AT(1) receptor blockade.
AB  - This study tested the hypothesis that endogenous bradykinin contributes to the
      effects of angiotensin AT(1) receptor blockade in humans. The effect of the
      bradykinin B(2) receptor antagonist d-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-d-Tic-Oic-Arg
      (HOE-140) (18 microg/kg/h i.v. for 6 h) on hemodynamic and endocrine responses to
      acute and chronic (1-month) treatment with valsartan (160 mg/day) was determined
      in 13 normotensive and 12 hypertensive salt-deplete subjects. Acute valsartan
      increased plasma renin activity (PRA) from 5.3 +/- 9.9 to 15.6 +/- 19.8 ng of
      angiotensin (Ang) I/ml/h (P < 0.001) and decreased aldosterone from 18.3 +/- 10.5
      to 12.0 +/- 9.6 ng/dl (P < 0.001). Chronic valsartan significantly increased
      baseline PRA (10.5 +/- 15.5 ng of Ang I/ml/h; P = 0.004) but did not affect
      baseline angiotensin-converting enzyme activity or aldosterone. HOE-140 tended to
      increase the PRA response to valsartan, and it attenuated the decrease in
      aldosterone following chronic valsartan (P = 0.03). Acute valsartan decreased
      mean arterial pressure 12.7 +/- 6.9% (from 100.2 +/- 8.4 to 87.5 +/- 9.8 mm Hg in
      hypertensives and from 82.4 +/- 8.6 to 70.3 +/- 8.4 mm Hg in normotensives). HOE
      140 did not affect the blood pressure response to either acute (effect of
      valsartan, P < 0.001; effect of HOE-140, P = 0.98) or chronic (valsartan, P =
      0.01; HOE-140, P = 0.84) valsartan. Plasma cGMP was increased significantly
      during chronic valsartan (P = 0.048) through a bradykinin receptor-independent
      mechanism (effect of HOE-140, P = 0.13). Both acute (P < 0.001) and chronic (P <
      0.001) valsartan increased heart rate. HOE-140 augmented the heart rate response
      to chronic valsartan (P = 0.04). These data suggest that endogenous bradykinin
      does not contribute significantly to the blood pressure-lowering effect of
      valsartan through its B(2) receptor.

PMID- 17182978
TI  - A 24-phenylsulfone analog of vitamin D inhibits 1alpha,25-dihydroxyvitamin D(3)
      degradation in vitamin D metabolism-competent cells.
AB  - The antimitotic, prodifferentiating, and proapoptotic steroid hormone, 1alpha,25
      dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)], at supraphysiological levels has
      potential for tumor therapy. However, epithelial cells from tumor-prone organs
      such as colon, prostate, and breast express not only the vitamin D receptor, but
      also vitamin D hydroxylases. In contrast to normal cells, malignant cells have
      high basal levels of the hydroxylase 25-hydroxyvitamin D(3)-24-hydroxylase
      (CYP24) and, in addition, have the potential to induce CYP24 in response to
      1alpha,25-(OH)(2)D(3). Because 24-hydroxylation by CYP24 would rapidly degrade
      the steroid hormone in the course of therapy, the enzyme activity in tumor cells
      should be inhibited. We demonstrate that a 24-phenylsulfone analog of 1alpha,25
      (OH)(2)D(3), KRC-24SO(2)Ph-1 (S-4a), rapidly and potently inhibits 24-hydroxylase
      activity in human tumor cells derived from colon, prostate, and mammary gland.
      Although enzymatic inhibition is a consequence of direct interaction, S-4a as a
      vitamin D analog apparently binds to the vitamin D receptor and induces CYP24
      mRNA, which, however, is not translated into increased enzymatic activity. 25
      Hydroxyvitamin D(3)-1alpha-hydroxylase expression is not affected at all by S-4a.
      When both 1alpha,25-(OH)(2)D(3) and S-4a are added to the cell culture,
      transcription of CYP24 is increased, possibly because of an increase in the half
      life of the hormone. The colon cell line COGA-13 has very high levels of CYP24
      and is, therefore, resistant to the action of vitamin D. Yet, S-4a imparts
      antimitotic activity to 1alpha,25-(OH)(2)D(3) and may therefore constitute a
      therapeutic to stimulate the antiproliferative potential of vitamin D-based
      antitumor activity.

PMID- 17182979
TI  - History of allergic disease and risk of meningioma.
AB  - Epidemiologic studies have consistently shown inverse associations of allergic
      disease with risk of glioma, but it is unclear whether this association also
      applies to meningioma. The authors conducted a pooled analysis of meningioma risk
      in relation to a history of allergic disease based on data from two population
      based, case-control studies with 475 cases and 1,716 controls in the United
      Kingdom (2001-2004). Meningioma risk was significantly reduced in relation to
      self-reported, physician-diagnosed allergic disease (odds ratio = 0.76, 95%
      confidence interval (CI): 0.61, 0.96) but was nonsignificantly reduced for
      individual conditions: asthma (odds ratio = 0.85, 95% CI: 0.61, 1.18), hay fever
      (odds ratio = 0.81, 95% CI: 0.62, 1.06), and eczema (odds ratio = 0.72, 95% CI:
      0.51, 1.02). Risk reductions were greatest for asthma (odds ratio = 0.43, 95% CI:
      0.21, 0.89) and hay fever (odds ratio = 0.50, 95% CI: 0.25, 1.00) with an early
      age at onset (<10 years) and for eczema (odds ratio = 0.46, 95% CI: 0.21, 1.07)
      with an onset at ages 10-19 years; they were near unity for onset in adulthood.
      This study suggests an inverse association between a history of allergies and
      meningioma risk, but with smaller risk reductions than for glioma. The reasons
      for this association need clarification, as well as an etiologic explanation.
      Consideration also needs to be given to confounding or bias.

PMID- 17182980
TI  - Fertility treatment and reproductive health of male offspring: a study of 1,925
      young men from the general population.
AB  - Little is known the about the reproductive health of offspring after fertility
      treatment. In 2001-2005, the authors approached young Danish men attending a
      compulsory physical examination to determine their fitness for military service.
      A total of 1,925 men volunteered, delivered a semen sample, had a physical
      examination performed and a blood sample drawn, and responded to a questionnaire.
      Their mothers were questioned about whether they had received fertility treatment
      in order to conceive their sons. Forty-seven mothers reported having received
      fertility treatment to conceive the index subject. After control for confounders,
      men whose mothers had received fertility treatment to conceive them had a 46%
      lower sperm concentration (95% confidence interval (CI): -63, -20) and a 45%
      lower total sperm count (95% CI: -64, -16). They had a smaller testis size (-0.9
      ml, 95% CI: -2.2, 0.4), fewer motile sperm (-4.0%, 95% CI: -8.0, -0.1), and fewer
      morphologically normal spermatozoa (-2.0%, 95% CI: -4.1, 0.0). They also had a
      lower serum testosterone level and free androgen index (results not statistically
      significant). These findings should be viewed in light of the increasing use of
      fertility treatments. Although the cause of these findings is unknown, they raise
      concern about possible late effects of fertility treatment. Larger-scale studies
      of children born after fertility treatment should be performed.

PMID- 17182981
TI  - Relaxing the rule of ten events per variable in logistic and Cox regression.
AB  - The rule of thumb that logistic and Cox models should be used with a minimum of
      10 outcome events per predictor variable (EPV), based on two simulation studies,
      may be too conservative. The authors conducted a large simulation study of other
      influences on confidence interval coverage, type I error, relative bias, and
      other model performance measures. They found a range of circumstances in which
      coverage and bias were within acceptable levels despite less than 10 EPV, as well
      as other factors that were as influential as or more influential than EPV. They
      conclude that this rule can be relaxed, in particular for sensitivity analyses
      undertaken to demonstrate adequate control of confounding.

PMID- 17182982
TI  - Method to assess identifiability in electronic data files.
AB  - The authors developed the Record Uniqueness (RU) software program to assess
      electronic data files for risk of confidentiality breach based on unique
      combinations of key variables. The underlying methodology utilized by the RU
      program generates a frequency distribution for every variable selected for
      analysis and for all combinations of the variables selected. In addition, the
      program provides the regression coefficient that designates the relative
      contribution of each variable to the unique records on the data file. The authors
      used RU to evaluate a North American Association of Central Cancer Registries
      research data set with 4.67 million cases from 34 population-based cancer
      registries for 1995-2001. To illustrate the process and utility of RU, they
      describe the evaluation process of the confidentiality risk of adding a county
      based socioeconomic measure to the research file. The RU method enables one to be
      assured of record confidentiality, provides flexibility to adjust record
      uniqueness thresholds for different users or purposes of data release, and
      facilitates good stewardship of confidential data balanced with maximum use and
      release of information for research. RU is a useful data tool that can quantify
      the risk of confidentiality breach of electronic health databases, including
      reidentifiability of cases through triangulation of information or linkage with
      other electronic databases.

PMID- 17182983
TI  - Childhood acute lymphoblastic leukemia and infections in the first year of life:
      a report from the United Kingdom Childhood Cancer Study.
AB  - The United Kingdom Childhood Cancer Study was designed to examine the relation
      between childhood cancer and preceding exposure to infectious diseases. The
      authors analyzed the relation between diagnosis (1991-1996) of acute
      lymphoblastic leukemia (ALL) at ages 2-5 years and clinically diagnosed
      infections in infancy. Almost all study children (96% of both cases and controls)
      were taken to a general practitioner for a non-immunization-associated visit at
      least once before their first birthday. Children diagnosed with ALL had
      significantly more clinically diagnosed infectious episodes in infancy than did
      controls; the average number of episodes was 3.6 (95% confidence interval (CI):
      3.3, 3.9) versus 3.1 (95% CI: 2.9, 3.2). This case-control difference was most
      apparent in the neonatal period (< or =1 month); 18% of controls and 24% of ALL
      cases were diagnosed with at least one infection (odds ratio = 1.4, 95% CI: 1.1,
      1.9; p < 0.05). Cases who had more than one neonatal infectious episode tended to
      be diagnosed with ALL at a comparatively young age; the mean age at ALL diagnosis
      was 37.7 months for cases with two or more episodes versus 45.3 months for cases
      with only one episode or none (p < 0.01). These findings support the hypothesis
      that a dysregulated immune response to infection in the first few months of life
      promotes transition to overt ALL later in childhood.

PMID- 17182984
TI  - Images in clinical medicine. Multiple pulmonary bacterial abscesses.

PMID- 17182985
TI  - Reconstructing lives--a tale of two soldiers.

PMID- 17182986
TI  - The limitations of risk factors as prognostic tools.

PMID- 17182987
TI  - A randomized trial of diagnostic techniques for ventilator-associated pneumonia.
AB  - BACKGROUND: Critically ill patients who require mechanical ventilation are at
      risk for ventilator-associated pneumonia. Current data are conflicting as to the
      optimal diagnostic approach in patients who have suspected ventilator-associated
      pneumonia. METHODS: In a multicenter trial, we randomly assigned immunocompetent
      adults who were receiving mechanical ventilation and who had suspected ventilator
      associated pneumonia after 4 days in the intensive care unit (ICU) to undergo
      either bronchoalveolar lavage with quantitative culture of the bronchoalveolar
      lavage fluid or endotracheal aspiration with nonquantitative culture of the
      aspirate. Patients known to be colonized or infected with pseudomonas species or
      methicillin-resistant Staphylococcus aureus were excluded. Empirical antibiotic
      therapy was initiated in all patients until culture results were available, at
      which point a protocol of targeted therapy was used for discontinuing or reducing
      the dose or number of antibiotics, or for resuming antibiotic therapy to treat a
      preenrollment condition if the culture was negative. RESULTS: We enrolled 740
      patients in 28 ICUs in Canada and the United States. There was no significant
      difference in the primary outcome (28-day mortality rate) between the
      bronchoalveolar-lavage group and the endotracheal-aspiration group (18.9% and
      18.4%, respectively; P=0.94). The bronchoalveolar-lavage group and the
      endotracheal-aspiration group also had similar rates of targeted therapy (74.2%
      and 74.6%, respectively; P=0.90), days alive without antibiotics (10.4+/-7.5 and
      10.6+/-7.9, P=0.86), and maximum organ-dysfunction scores (mean [+/-SD], 8.3+/
      3.6 and 8.6+/-4.0; P=0.26). The two groups did not differ significantly in the
      length of stay in the ICU or hospital. CONCLUSIONS: Two diagnostic strategies for
      ventilator-associated pneumonia--bronchoalveolar lavage with quantitative culture
      of the bronchoalveolar-lavage fluid and endotracheal aspiration with
      nonquantitative culture of the aspirate--are associated with similar clinical
      outcomes and similar overall use of antibiotics. (Current Controlled Trials
      number, ISRCTN51767272 [controlled-trials.com].).

PMID- 17182988
TI  - Multiple biomarkers for the prediction of first major cardiovascular events and
      death.
AB  - BACKGROUND: Few investigations have evaluated the incremental usefulness of
      multiple biomarkers from distinct biologic pathways for predicting the risk of
      cardiovascular events. METHODS: We measured 10 biomarkers in 3209 participants
      attending a routine examination cycle of the Framingham Heart Study: the levels
      of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial
      natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen
      activator inhibitor type 1, and homocysteine; and the urinary albumin-to
      creatinine ratio. RESULTS: During follow-up (median, 7.4 years), 207 participants
      died and 169 had a first major cardiovascular event. In Cox proportional-hazards
      models adjusting for conventional risk factors, the following biomarkers most
      strongly predicted the risk of death (each biomarker is followed by the adjusted
      hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide
      level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine
      ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers
      that most strongly predicted major cardiovascular events were B-type natriuretic
      peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values)
      and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker"
      scores (based on regression coefficients of significant biomarkers) in the
      highest quintile as compared with those with scores in the lowest two quintiles
      had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major
      cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the
      addition of multimarker scores to conventional risk factors resulted in only
      small increases in the ability to classify risk, as measured by the C statistic.
      CONCLUSIONS: For assessing risk in individual persons, the use of the 10
      contemporary biomarkers that we studied adds only moderately to standard risk
      factors.

PMID- 17182989
TI  - Ertapenem versus cefotetan prophylaxis in elective colorectal surgery.
AB  - BACKGROUND: Ertapenem, a long-acting carbapenem, may be an alternative to the
      recommended prophylactic antibiotic cefotetan. METHODS: In this randomized,
      double-blind trial, we assessed the efficacy and safety of antibiotic prophylaxis
      with ertapenem, as compared with cefotetan, in patients undergoing elective
      colorectal surgery. A successful outcome was defined as the absence of surgical
      site infection, anastomotic leakage, or antibiotic use 4 weeks postoperatively.
      All adverse events were collected until 14 days after the administration of
      antibiotic prophylaxis. RESULTS: Of the 1002 patients randomly assigned to study
      groups, 901 (451 in the ertapenem group and 450 in the cefotetan group) qualified
      for the modified intention-to-treat analysis, and 672 (338 in the ertapenem group
      and 334 in the cefotetan group) were included in the per-protocol analysis. After
      adjustment for strata, in the modified intention-to-treat analysis, the rate of
      overall prophylactic failure was 40.2% in the ertapenem group and 50.9% in the
      cefotetan group (absolute difference, -10.7%; 95% confidence interval [CI], -17.1
      to -4.2); in the per-protocol analysis, the failure rate was 28.0% in the
      ertapenem group and 42.8% in the cefotetan group (absolute difference, -14.8%;
      95% CI, -21.9 to -7.5). Both analyses fulfilled statistical criteria for the
      superiority of ertapenem. In the modified intention-to-treat analysis, the most
      common reason for failure of prophylaxis in both groups was surgical-site
      infection: 17.1% in the ertapenem group and 26.2% in the cefotetan group
      (absolute difference, -9.1; 95% CI, -14.4 to -3.7). In the treated population,
      the overall incidence of Clostridium difficile infection was 1.7% in the
      ertapenem group and 0.6% in the cefotetan group (P=0.22). CONCLUSIONS: Ertapenem
      is more effective than cefotetan in the prevention of surgical-site infection in
      patients undergoing elective colorectal surgery but may be associated with an
      increase in C. difficile infection. (ClinicalTrials.gov number, NCT00090272
      [ClinicalTrials.gov].).

PMID- 17182990
TI  - PET of brain amyloid and tau in mild cognitive impairment.
AB  - BACKGROUND: Amyloid senile plaques and tau neurofibrillary tangles are
      neuropathological hallmarks of Alzheimer's disease that accumulate in the
      cortical regions of the brain in persons with mild cognitive impairment who are
      at risk for Alzheimer's disease. Noninvasive methods to detect these abnormal
      proteins are potentially useful in developing surrogate markers for drug
      discovery and diagnostics. METHODS: We enrolled 83 volunteers with self-reported
      memory problems who had undergone neurologic and psychiatric evaluation and
      positron-emission tomography (PET). On the basis of cognitive testing, 25
      volunteers were classified as having Alzheimer's disease, 28 as having mild
      cognitive impairment, and 30 as having no cognitive impairment (healthy
      controls). PET was performed after injection of 2-(1-{6-[(2-[F
      18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a
      molecule that binds to plaques and tangles in vitro. All subjects also underwent
      2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET, and 72 underwent magnetic resonance
      imaging (MRI). RESULTS: Global values for FDDNP-PET binding (average of the
      values for the temporal, parietal, posterior cingulate, and frontal regions) were
      lower in the control group than in the group with mild cognitive impairment
      (P<0.001), and the values for binding in the group with mild cognitive impairment
      were lower than in the group with Alzheimer's disease (P<0.001). FDDNP-PET
      binding differentiated among the diagnostic groups better than did metabolism on
      FDG-PET or volume on MRI. CONCLUSIONS: FDDNP-PET scanning can differentiate
      persons with mild cognitive impairment from those with Alzheimer's disease and
      those with no cognitive impairment. This technique is potentially useful as a
      noninvasive method to determine regional cerebral patterns of amyloid plaques and
      tau neurofibrillary tangles.

PMID- 17182991
TI  - Teaching surgical skills--changes in the wind.

PMID- 17182992
TI  - Autoimmune pancreatitis.

PMID- 17182993
TI  - Images in clinical medicine. Disseminated paracoccidioidomycosis and coinfection
      with HIV.

PMID- 17182994
TI  - Case records of the Massachusetts General Hospital. Case 39-2006. A 24-year-old
      woman with systemic lupus erythematosus, seizures, and right arm weakness.

PMID- 17182995
TI  - Diagnosis of ventilator-associated pneumonia.

PMID- 17182996
TI  - Carbapenems for surgical prophylaxis?

PMID- 17182997
TI  - Technical-skills training in the 21st century.

PMID- 17182998
TI  - The persistence of memory.

PMID- 17182999
TI  - Overweight, obesity, and mortality.

PMID- 17183000
TI  - Body-mass index and mortality in Korean men and women.

PMID- 17183001
TI  - Social anxiety disorder.

PMID- 17183002
TI  - Cerebral aneurysms.

PMID- 17183003
TI  - Cancer stem cells.

PMID- 17183004
TI  - Use of statins and outcome of BCG treatment for bladder cancer.

PMID- 17183005
TI  - Sharing hypotheses and ideas in public health research: contributing to the
      research agenda.

PMID- 17183006
TI  - Neighbourhood influences on health.

PMID- 17183007
TI  - A glossary for the social epidemiology of work organisation: part 3, terms from
      the sociology of labour markets.

PMID- 17183008
TI  - Why do peer reviewers decline to review? A survey.
AB  - BACKGROUND: Peer reviewers are usually unpaid and their efforts not formally
      acknowledged. Some journals have difficulty finding appropriate reviewers able to
      complete timely reviews, resulting in publication delay. OBJECTIVES AND METHODS:
      A survey of peer reviewers from five biomedical journals was conducted to
      determine why reviewers decline to review and their opinions on reviewer
      incentives. Items were scored on 5-point Likert scales, with low scores
      indicating low importance or low agreement. RESULTS: 551/890 (62%) reviewers
      responded. Factors rated most highly in importance for the decision to accept to
      review a paper included contribution of the paper to subject area (mean 3.67
      (standard deviation (SD) 86)), relevance of topic to own work (mean 3.46 (SD
      0.99)) and opportunity to learn something new (mean 3.41 (SD 0.96)). The most
      highly rated factor important in the decision to decline to review was conflict
      with other workload (mean 4.06 (SD 1.31)). Most respondents agreed that financial
      incentives would not be effective when time constraints are prohibitive (mean
      3.59 (SD 1.01)). However, reviewers agreed that non-financial incentives might
      encourage reviewers to accept requests to review: free subscription to journal
      content (mean 3.72 (SD 1.04)), annual acknowledgement on the journal's website
      (mean 3.64 (SD 0.90)), more feedback about the outcome of the submission (mean
      3.62 (SD 0.88)) and quality of the review (mean 3.60 (SD 0.89), and appointment
      of reviewers to the journal's editorial board (mean 3.57 (SD 0.99)). CONCLUSION:
      Reviewers are more likely to accept to review a manuscript when it is relevant to
      their area of interest. Lack of time is the principal factor in the decision to
      decline. Reviewing should be formally recognised by academic institutions and
      journals should acknowledge reviewers' work.

PMID- 17183010
TI  - Does the UK government's teenage pregnancy strategy deal with the correct risk
      factors? Findings from a secondary analysis of data from a randomised trial of
      sex education and their implications for policy.
AB  - BACKGROUND: Much of the UK government's 1999 report on teenage pregnancy was by
      necessity based on rather old or non-longitudinal research. AIM: To examine the
      associations between risk factors identified in the report and pregnancy at or
      before age 16 years among young women and partners of young men using the more
      recent data. RESULTS: Socioeconomic disadvantage, being born to a teenage mother,
      expectation of being a teenage parent, low educational expectations and various
      other behaviours are potential risk factors for teenage pregnancy, as suggested
      by unadjusted analyses. Those who cited school as providing information on sex
      had a reduced risk of pregnancy at or before age 16 years, as did girls reporting
      easy communication with parent or guardian at baseline. Various measures of low
      sexual health knowledge were not associated, in either adjusted or unadjusted
      analyses, with increased risk of pregnancy at or before age 16 years among boys
      or girls. CONCLUSIONS: A focus on many of the risk factors identified in the 1999
      report is supported herein. It is suggested that knowledge may not be an
      important determinant, but that relationships with parents and school, as well as
      expectations for the future, may have important influences on teenage pregnancy.
      The analysis also provides new insights into risk factors for pregnancies among
      the partners of young men.

PMID- 17183009
TI  - Do places affect the probability of death in Australia? A multilevel study of
      area-level disadvantage, individual-level socioeconomic position and all-cause
      mortality, 1998-2000.
AB  - BACKGROUND: In Australia, studies finding an association between area-level
      socioeconomic disadvantage and mortality are often based on aggregate-ecological
      designs which confound area-level and individual-level sources of socioeconomic
      variation. Area-level socioeconomic differences in mortality therefore may be an
      artefact of varying population compositions and not the characteristics of areas
      as such. OBJECTIVE: To examine the associations between area-level disadvantage
      and all-cause mortality before and after adjustment for within-area variation in
      individual-level socioeconomic position (SEP) using unlinked census and mortality
      register data in a multilevel context. Setting, participants and DESIGN: The
      study covers the total Australian continent for the period 1998-2000 and is based
      on decedents aged 25-64 years (n = 43,257). The socioeconomic characteristics of
      statistical local areas (SLA, n = 1317) were measured using an index of relative
      socioeconomic disadvantage, and individual-level SEP was measured by occupation.
      RESULTS: Living in a disadvantaged SLA was associated with higher all-cause
      mortality after adjustment for within-SLA variation in occupation. Death rates
      were highest for blue-collar workers and lowest among white-collar employees.
      Cross-level interactions showed no convincing evidence that SLA disadvantage
      modified the extent of inequality in mortality between the occupation groups.
      CONCLUSIONS: Multilevel analysis can be used to examine area variation in
      mortality using unlinked census and mortality data, therefore making it less
      necessary to use aggregate-ecological designs. In Australia, area-level and
      individual-level socioeconomic factors make an independent contribution to the
      probability of premature mortality. Policies and interventions to improve
      population health and reduce mortality inequalities should focus on places as
      well as people.

PMID- 17183011
TI  - Thailand--lighting up a dark market: British American tobacco, sports sponsorship
      and the circumvention of legislation.
AB  - OBJECTIVE: To examine how British American Tobacco (BAT) used sports sponsorship
      to circumvent restrictions on tobacco promotion in Thailand, both a key emerging
      market and a world leader in tobacco control. METHOD: Analysis of previously
      confidential BAT company documents. RESULTS: Since its inception in 1987, BAT's
      sports sponsorship programme in Thailand has been politically sensitive and
      legally ambiguous. Given Thailand's ban on imported cigarettes, early events
      provided promotional support to smuggled brands. BAT's funding of local
      badminton, snooker, football and cricket tournaments generated substantial media
      coverage for its brands. After the General Agreement on Trade and Tariffs
      decision that obliged Thailand to open its cigarette market to imports,
      Thailand's 1992 tobacco control legislation established one of the world's most
      restrictive marketing environments. BAT's sponsorship strategy shifted to
      rallying and motorbike racing, using broadcasts of regional competitions to
      undermine national regulations. BAT sought to dominate individual sports and to
      shape media coverage to maximise brand awareness. An adversarial approach was
      adopted, testing the limits of legality and requiring active enforcement to
      secure compliance with legislation. CONCLUSIONS: The documents show the
      opportunities offered by sports sponsorship to tobacco companies amid increasing
      advertising restrictions. Before the 1992 tobacco control legislation, sponsored
      events in Thailand promoted international brands by combining global and local
      imagery. The subsequent strategy of "regionalisation as defensibility" reflected
      the capacity of international sport to transcend domestic restrictions. These
      transnational effects may be effectively dealt with via the Framework Convention
      on Tobacco Control, but will require the negotiation of a specific protocol.

PMID- 17183012
TI  - The population effect of crime and neighbourhood on physical activity: an
      analysis of 15,461 adults.
AB  - Area-based interventions offer the potential to increase physical activity for
      many sedentary people in countries such as the UK. Evidence on the effect of
      individual and area/neighbourhood influences on physical activity is in its
      infancy, and despite its value to policy makers a population focus is rarely
      used. Data from a population-based health and lifestyle survey of adults in
      northwest England were used to analyse associations between individual and
      neighbourhood perceptions and physical activity. The population effect of
      eliminating a risk factor was expressed as a likely effect on population levels
      of physical activity. Of the 15,461 responders, 21,923 (27.1%) were physically
      active. Neighbourhood perceptions of leisure facilities were associated with
      physical activity, but no association was found for sense of belonging, public
      transport or shopping facilities. People who felt safe in their neighbourhood
      were more likely to be physically active, but no associations were found for
      vandalism, assaults, muggings or experience of crime. The number of physically
      active people would increase by 3290 if feelings of "unsafe" during the day were
      removed, and by 11,237 if feelings of "unsafe" during the night were removed. An
      additional 8342 people would be physically active if everyone believed that they
      were "very well placed for leisure facilities". Feeling safe had the potential
      largest effect on population levels of physical activity. Strategies to increase
      physical activity in the population need to consider the wider determinants of
      health-related behaviour, including fear of crime and safety.

PMID- 17183013
TI  - Patient centredness.

PMID- 17183014
TI  - Validity of an adaptation of the Framingham cardiovascular risk function: the
      VERIFICA Study.
AB  - BACKGROUND: To assess the reliability and accuracy of the Framingham coronary
      heart disease (CHD) risk function adapted by the Registre Gironi del Cor
      (REGICOR) investigators in Spain. METHODS: A 5-year follow-up study was completed
      in 5732 participants aged 35-74 years. The adaptation consisted of using in the
      function the average population risk factor prevalence and the cumulative
      incidence observed in Spain instead of those from Framingham in a Cox
      proportional hazards model. Reliability and accuracy in estimating the observed
      cumulative incidence were tested with the area under the curve comparison and
      goodness-of-fit test, respectively. RESULTS: The Kaplan-Meier CHD cumulative
      incidence during the follow-up was 4.0% in men and 1.7% in women. The original
      Framingham function and the REGICOR adapted estimates were 10.4% and 4.8%, and
      3.6% and 2.0%, respectively. The REGICOR-adapted function's estimate did not
      differ from the observed cumulated incidence (goodness of fit in men, p = 0.078,
      in women, p = 0.256), whereas all the original Framingham function estimates
      differed significantly (p<0.001). Reliabilities of the original Framingham
      function and of the best Cox model fit with the study data were similar in men
      (area under the receiver operator characteristic curve 0.68 and 0.69,
      respectively, p = 0.273), whereas the best Cox model fitted better in women (0.73
      and 0.81, respectively, p<0.001). CONCLUSION: The Framingham function adapted to
      local population characteristics accurately and reliably predicted the 5-year CHD
      risk for patients aged 35-74 years, in contrast with the original function, which
      consistently overestimated the actual risk.

PMID- 17183015
TI  - Psychological distress after employment transitions: the role of subjective
      financial position as a mediator.
AB  - OBJECTIVE: To explore the extent to which the mental health effects of
      transitions into unemployment, or other forms of non-employment, and vice versa,
      are mediated by financial changes. METHODS: Longitudinal analysis of the British
      Household Panel Survey from 1991 to 2000. There were 89,264 person-years of
      observation from 14,686 individuals aged > or =16 years. Main outcome measure was
      psychological distress measured by the 12-item General Health Questionnaire.
      RESULTS: Transitions to unemployment were associated with increased risk of
      psychological distress for men (adjusted odds ratio (OR) 3.15 (95% confidence
      interval (CI) 2.50 to 3.98)) and for women (OR 2.60 (95% CI 1.97 to 3.43)). Women
      who left work to look after the family were also more likely to experience
      psychological distress (OR 1.72 (95% CI 1.45 to 2.05)). A reduced risk of
      psychological distress was seen for transitions from unemployment to paid
      employment for men (OR 0.52 (95% CI 0.41 to 0.68)) and for women (OR 0.68 (95% CI
      0.69 to 1.40)). Financial difficulty partially mediated these relationships: men
      who became unemployed and were worse off financially were more likely to
      experience psychological distress (OR 4.19 (95% CI 3.20 to 5.50)) than men who
      were not (OR 1.48 (95% CI 0.95 to 2.33)). Conversely, the beneficial health
      effect for people who left unemployment and became employed was confined to those
      who were better off financially (OR 0.34 (0.25 to 0.48) for men). CONCLUSIONS:
      Changes in employment status have both direct and indirect effects, through
      changes in financial circumstances, on subsequent psychological distress. The
      results support the view that the direction of causation runs from employment
      transitions to financial difficulties and psychological distress.

PMID- 17183016
TI  - Association of low blood pressure with anxiety and depression: the Nord-Trondelag
      Health Study.
AB  - BACKGROUND: Low blood pressure has mainly been regarded as ideal, but recent
      studies have indicated an association with depression in elderly people.
      OBJECTIVE: To investigate whether low blood pressure is associated with anxiety
      and depression in the general population. DESIGN: Cross-sectional study. SETTING:
      Participants in the population-based Nord-Trondelag Health Study (HUNT-2, 1995
      7), Norway. PARTICIPANTS: 60,799 men and women aged 20-89 years filled in the
      Hospital Anxiety and Depression Scale as part of a general health study. Systolic
      and diastolic blood pressure was classified in age-stratified and sex-stratified
      centile groups. MAIN RESULTS: Compared with participants with systolic blood
      pressure within the 41-60 centile (reference) group, the odds ratio for anxiety
      was 1.31 (95% confidence intervals (CI) 1.16 to 1.49), for depression 1.22 (95%
      CI 1.03 to 1.46), and for comorbid anxiety and depression 1.44 (95% CI 1.24 to
      1.68) in the group with < or =5 centile systolic blood pressure. Slightly weaker
      associations were found of low diastolic blood pressure with anxiety and
      depression. These associations were similar across sex and age groups. Physical
      impairment, smoking and angina pectoris influenced the associations only
      marginally, whereas stroke, myocardial infarction, use of drugs for hypertension,
      body mass index and several other covariates had no influence. CONCLUSIONS: This
      study represents epidemiological evidence for an association of low blood
      pressure with anxiety and depression, which is not caused by cardiovascular
      disease.

PMID- 17183017
TI  - Cancer is overtaking cardiovascular disease as the main driver of socioeconomic
      inequalities in mortality: New Zealand (1981-99).
AB  - BACKGROUND: Relative socioeconomic disparities in cardiovascular mortality have
      increased in New Zealand, as in many Western countries in Northern Europe, the US
      and Australia during the late 20th century. However, substantial declines in
      cardiovascular mortality mean that its absolute contribution to overall mortality
      has decreased. RESEARCH QUESTIONS: How did the absolute contribution of major
      causes of death to socioeconomic inequalities in New Zealand change during the
      1980s and 90s? METHODS: Linked census-mortality cohorts were used to calculate
      the contribution of different causes of death to inequalities in mortality,
      measured with the slope index of inequality, by household income. RESULTS:
      Between 1981-4 and 1996-9, the contribution of cardiovascular disease (CVD) to
      total inequality declined from 55% to 28% among women, whereas at the same time
      the contribution of cancers increased from 14% to 37%. Among men, the
      contribution of CVD to total inequality peaked at 47% in 1986-9, then declined to
      38% in 1996-9. The contribution of cancer increased from 19% to 26% in men.
      CONCLUSION: CVD mortality has declined at all income levels and so too has the
      contribution of CVD to mortality inequalities. Concurrently, the contribution of
      cancer to inequalities in mortality by income has increased and, in women at
      least, is now greater than the contribution of CVD. It is hypothesised that a
      similar crossover is occurring in other populations where CVD mortality has
      declined, although socioeconomic differences in the distribution and effect of
      the obesity epidemic for CVD may ensure its continuing importance. Prevention
      efforts aimed at reducing socioeconomic inequalities in mortality will need to
      increasingly focus on socioeconomic inequalities in cancer mortality.

PMID- 17183018
TI  - Association of metabolic syndrome and insulin resistance with congestive heart
      failure: findings from the Third National Health and Nutrition Examination
      Survey.
AB  - OBJECTIVE: Congestive heart failure (CHF) has been associated with insulin
      resistance, but few studies have examined its relationship with metabolic
      syndrome (MetS). Little is known about whether insulin resistance explains the
      association between MetS and CHF. DESIGN: Population-based, cross-sectional
      surveys. SETTING: Third National Health and Nutrition Examination Survey (NHANES
      III). PARTICIPANTS: Data from 5549 men and non-pregnant women aged > or =40 years
      in NHANES III were analysed. RESULTS: About 4% of men and 3% of women had CHF
      between 1988 and 1994 in the US. The age-adjusted prevalence of CHF was
      significantly higher in African Americans (4.1%), in Mexican Americans (8.5%) and
      in those of other ethnic origin (6.7%) than in white people (2.5%). People with
      MetS had nearly twice the likelihood of self-reported CHF (adjusted odds ratio
      1.8; 95% confidence interval 1.1 to 3.0) after adjustment for demographic and
      conventional risk factors such as sex, ethnicity, age, smoking, total
      cholesterol, left ventricular hypertrophy, and probable or possible myocardial
      infarction determined by electrocardiography. However, this association was
      attenuated after further adjustment for insulin resistance as measured by the
      homoeostasis model assessment (HOMA). >90% of the association between MetS and
      CHF was explained by the HOMA. CONCLUSIONS: MetS was associated with about a
      twofold increased likelihood of self-reported CHF and it may serve as a surrogate
      indicator for the association between insulin resistance and CHF.

PMID- 17183019
TI  - Eye discomfort, headache and back pain among Mayan Guatemalan women taking part
      in a randomised stove intervention trial.
AB  - BACKGROUND: Indoor air pollution (IAP) from combustion of biomass fuels
      represents a global health problem, estimated to cause 1.6 million premature
      deaths annually. AIMS: RESPIRE (Randomised Exposure Study of Pollution Indoors
      and Respiratory Effects) Guatemala is the first randomised controlled trial ever
      performed on health effects from solid fuel use. Its goal is to assess the effect
      of improved stoves (planchas) on exposure and health outcomes in a rural
      population reliant on wood fuel. METHODS: Questions about symptoms were asked at
      baseline and periodically after the intervention, to an initial group of 504
      women (259 randomly assigned to planchas (mean (standard deviation) age 27.4
      (7.2) years) and 245 using traditional open fires (28.1 (7.1) years)). Levels of
      carbon monoxide (CO) in exhaled breath, a biomarker of recent exposure to air
      pollution from biomass combustion, were measured at each visit. In addition to
      reducing IAP levels, the plancha may also have a positive health effect by
      changing the working posture to an upright position. RESULTS: A high prevalence
      of eye discomfort, headache and backache was found. The odds of having sore eyes
      and headache were substantially reduced in the plancha group relative to the
      group using open fires for the follow-up period (odds ratio (OR) 0.18, 95%
      confidence interval (CI) 0.11 to 0.29 and (OR) 0.63, 95% CI 0.42 to 0.94,
      respectively). Median CO in breath among women in the intervention trial was
      significantly lower than controls. CONCLUSION: In addition to reducing discomfort
      for women, tangible improvements in symptoms experienced by a substantial
      proportion of women may help to gain acceptance and wider use of planchas.

PMID- 17183020
TI  - Familial risks for nerve, nerve root and plexus disorders in siblings based on
      hospitalisations in Sweden.
AB  - BACKGROUND: Nerve, nerve root and plexus disorders are common diseases, but
      little is known about familial clustering in these diseases. This is, to our
      knowledge, the first systematic family study carried out on these diseases.
      METHODS: Familial risks for siblings who were hospitalised for nerve, nerve root
      and plexus disorders in Sweden were defined. A nationwide database for
      neurological diseases was constructed by linking the Multigeneration Register on
      0-69-year-old siblings to the Hospital Discharge Register covering the years 1987
      2001. Standardised risk ratios (SIRs) were calculated for affected sibling pairs
      by comparing them with those whose siblings had no neurological disease. RESULTS:
      29,686 patients, 43% men and 57% women, were diagnosed at a mean age of 37.5
      years. 191 siblings were hospitalised for these disorders, giving an overall SIR
      of 2.59 (95% CI 1.58 to 4.22), with no sex difference. Plantar nerve mononeuritis
      and carpal tunnel syndrome showed the highest familial risks: 4.82 (1.08 to
      16.04) and 4.08 (2.07 to 7.84), respectively. Lateral poplitean and plantar nerve
      neuritis preferentially affected women, with SIRs of >8; disorders of the other
      cranial nerves affected only men, with an SIR of >10. Concordant trigeminal
      neuralgia, Bell's palsy and carpal tunnel syndrome showed familial risks, but,
      with the exception of Bell's palsy, they also showed correlation between spouses,
      implying environmental sharing of risk factors. CONCLUSIONS: The results cannot
      distinguish between inheritable or shared environmental factors, or their
      interactions, but they clearly show familial clustering, suggestive of
      multifactorial aetiology and inviting for aetiological research.

PMID- 17183021
TI  - The association of the paraoxonase (PON1) Q192R polymorphism with depression in
      older women: findings from the British Women's Heart and Health Study.
AB  - BACKGROUND: The association between the R allele of PON1 Q192R and symptoms
      reported by sheep dippers and Gulf War veterans has been used to suggest a
      biological basis for these symptoms. In the absence of such studies in non
      occupational populations, these conclusions may not be valid. OBJECTIVE: To
      examine the association of paraoxonase (PON1) Q192R with a report of ever being
      diagnosed with depression among a random sample of 3266 British women, aged 60-79
      years. RESULTS: The R allele of PON1 Q192R was associated with depression: per
      allele odds ratio 1.22 (95% confidence interval: 1.05 to 1.41) in this
      population. CONCLUSIONS: These findings suggest that the association of PON1
      Q192R with symptoms of depression in occupationally exposed groups may be driven
      by exposure to toxins that everyone in the general population is exposed to
      rather than exposure to toxins specifically used by sheep dippers or Gulf War
      veterans, or that other mechanisms underlie the association. This is because the
      study population in which we have found an association consisted of British women
      aged 60-79 years, few of whom were sheep dippers or Gulf War veterans. When using
      genotype-outcome associations to infer causality with respect to an environmental
      exposure modified by the genotype, it is important to examine these associations
      in general populations and in those specifically exposed to the putative agent.
      The possible role of PON1 Q192R in psychiatric morbidity requires further
      examination.

PMID- 17183024
TI  - Role of LCAT in HDL remodeling: investigation of LCAT deficiency states.
AB  - To better understand the role of LCAT in HDL metabolism, we compared HDL
      subpopulations in subjects with homozygous (n = 11) and heterozygous (n = 11)
      LCAT deficiency with controls (n = 22). Distribution and concentrations of
      apolipoprotein A-I (apoA-I)-, apoA-II-, apoA-IV-, apoC-I-, apoC-III-, and apoE
      containing HDL subpopulations were assessed. Compared with controls, homozygotes
      and heterozygotes had lower LCAT masses (-77% and -13%), and LCAT activities (
      99% and -39%), respectively. In homozygotes, the majority of apoA-I was found in
      small, disc-shaped, poorly lipidated prebeta-1 and alpha-4 HDL particles, and
      some apoA-I was found in larger, lipid-poor, discoidal HDL particles with alpha
      mobility. No apoC-I-containing HDL was noted, and all apoA-II and apoC-III was
      detected in lipid-poor, prebeta-mobility particles. ApoE-containing particles
      were more disperse than normal. ApoA-IV-containing particles were normal.
      Heterozygotes had profiles similar to controls, except that apoC-III was found
      only in small HDL with prebeta-mobility. Our data are consistent with the
      concepts that LCAT activity: 1) is essential for developing large, spherical,
      apoA-I-containing HDL and for the formation of normal-sized apoC-I and apoC-III
      HDL; and 2) has little affect on the conversion of prebeta-1 into alpha-4 HDL,
      only slight effects on apoE HDL, and no effect on apoA-IV HDL particles.

PMID- 17183025
TI  - An unusual cause of chest pain: foreign body in the oesophagus.
AB  - This article reports on two patients with unsuspected oesophageal foreign body
      ingestion, with chest pain as the main symptom. The patients had extensive
      cardiac evaluation to rule out myocardial ischaemia. Further evaluation showed an
      impacted oesophageal foreign body. Oesophageal foreign bodies should be
      considered as factors in chest pain.

PMID- 17183026
TI  - Factitious hyperamylasuria by a nurse: symptom of Munchausen's syndrome.
AB  - A 30-year-old nurse presented with abdominal pain and tenderness. Her blood
      tests, including amylase, were normal. Urinary amylase was extremely high. The
      source of the increased urinary amylase was found to be the patient's saliva -
      she had spit into her urine sample. Subsequent investigation showed that she had
      Munchausen's syndrome.

PMID- 17183027
TI  - "Hitting the nail on the head".
AB  - Subungual malignant melanoma is a rare form of malignancy that can present at an
      advanced stage. We describe a case that was diagnosed after a presentation to the
      emergency department for a traumatic injury of the affected area. Initial
      presentations of malignant disease and its complications form a relatively low
      proportion of the caseload of emergency doctors. In this case, a patient
      presented after a minor injury that had failed to recover; subsequent
      investigation of this injury led to the diagnosis of subungual malignant melanoma
      in an otherwise asymptomatic patient. This is a rare case which presented in an
      atypical fashion, with a confounding history of minor trauma. It is presented to
      highlight the differential diagnosis of destructive bone lesions.

PMID- 17183028
TI  - Brugada-like electrocardiographic changes induced by fever.
AB  - As "time is myocardium" in the settings of acute myocardial infarction, it is
      important to make the diagnosis as quickly as possible, and a high clinical
      suspicion is needed to avoid missing the diagnosis, resulting in unwarranted
      interventions. The electrocardiogram is a crucial tool in the identification of
      acute chest pain, enabling a detailed analysis of patterns of ST-segment
      elevation. We describe the case of a 22-year-old man who presented with fever,
      with dynamic electrocardiographic changes similar to the Brugada syndrome. These
      electrocardiographic anomalies disappeared when the temperature returned to
      normal.

PMID- 17183029
TI  - Back pain as the presenting symptom of generalised tetanus.
AB  - Back pain is a common presenting symptom in emergency departments and primary
      care across the UK. The extensive differential diagnosis includes mechanical,
      infective, thoracic, abdominal and vascular causes. This case report describes a
      patient who presented with lower back pain with a rare diagnosis, which is
      becoming more common in certain population groups, and emphasises the importance
      of clinical skills and insuring adequate tetanus prophylaxis.

PMID- 17183030
TI  - Bilateral posterior dislocation of the crystalline lens after a head injury
      sustained during a seizure.
AB  - This article presents a case of bilateral posterior dislocations of the
      crystalline lens in a patient with epilepsy who presented with reduced vision and
      anisocoria 2 weeks after having sustained head injuries during a seizure. The
      possibility of lens dislocation was raised only at this time, and subsequently
      confirmed on computed tomography. Such patients may require prompt referral to
      the ophthalmologist to treat complications such as functional aphakia, uveitis
      and more seriously pupillary block glaucoma. This case highlights the importance
      of ocular examination of head injuries to rule out possible ophthalmological
      pathology.

PMID- 17183031
TI  - Urgent care: is this the future? Probably.

PMID- 17183032
TI  - Fluid replacement via the rectum for treatment of hypovolaemic shock in an animal
      model.

PMID- 17183033
TI  - Does emergency medicine in the UK have a future?

PMID- 17183034
TI  - The use of classroom training and simulation in the training of medical
      responders for airport disaster.
AB  - There is a dire need to have complementary form of disaster training which is
      cost effective, relatively easy to conduct, comprehensive, effective and
      acceptable. This will complement field drills training. A classroom-based
      training and simulation module was built by combining multiple tools: Powerpoint
      lectures, simulations utilising the Kuala Lumpur International Airport (KLIA)
      schematic module into 'floortop' model and video show of previous disaster drill.
      76 participants made up of medical responders, categorised as Level 1
      (specialists and doctors), Level 2 (paramedics), Level 3 (assistant paramedics)
      and Level 4 (health attendants and drivers) were trained using this module. A pre
      test with validated questions on current airport disaster plans was carried out
      before the training. At the end of training, participants answered similar
      questions as post-test. Participants also answered questionnaire for assessment
      of training's acceptance. There was a mean rise from 47.3 (18.8%) to 84.0 (18.7%)
      in post-test (p<0.05). For Levels 1, 2, 3 and 4 the scores were 94.8 (6.3)%, 90.1
      (11)%, 80.3 (20.1)% and 65 (23.4)% respectively. Nevertheless Level 4 group
      gained most increase in knowledge rise from baseline pre-test score (51.4%).
      Feedback from the questionnaire showed that the training module was highly
      acceptable. A classroom-based training can be enhanced with favourable results.
      The use of classroom training and simulation effectively improves the knowledge
      of disaster plan significantly on the back of its low cost, relatively-easy to
      conduct, fun and holistic nature. All Levels of participants (from specialists to
      drivers) can be grouped together for training. Classroom training and simulation
      can overcome the problem of "dead-document" phenomenon or "paper-plan syndrome".

PMID- 17183035
TI  - The psychological effect of severe acute respiratory syndrome on emergency
      department staff.
AB  - BACKGROUND: The severe acute respiratory syndrome (SARS) outbreak in 2003
      affected 29 countries. The SARS outbreak was unique in its rapid transmission and
      it resulted in heavy stress in first-line healthcare workers, particularly in the
      emergency department. AIM: : To determine the influence of SARS on the
      psychological status, including post-traumatic stress disorder (PTSD) symptoms,
      of the staff in the emergency department. METHODS: To investigate whether
      different working conditions in the hospital led to different psychological
      effects on healthcare workers, the psychological effect on emergency department
      staff in the high-risk ward was compared with that on psychiatric ward staff in
      the medium-risk ward. Davidson Trauma Scale-Chinese version (DTS-C) and Chinese
      Health Questionnaire-12 (CHQ-12) items were designed to check the psychological
      status of the staff in the month after the end of the SARS outbreak. RESULTS: 86
      of 92 (93.5%) medical staff considered the SARS outbreak to be a traumatic
      experience. The DTS-C scores of staff in the emergency department and in the
      psychiatric ward were significantly different (p = 0.04). No significant
      difference in CHQ score was observed between the two groups. Emergency department
      staff had more severe PTSD symptoms than staff in the psychiatric ward.
      CONCLUSION: SARS was a traumatic experience for healthcare providers in Taiwan.
      Most staff in the emergency department and in the psychiatric ward had PTSD.
      Emergency department staff had more severe PTSD symptoms than staff in the
      psychiatric ward.

PMID- 17183036
TI  - Post-war development of emergency medicine in Kosovo.
AB  - OBJECTIVES: To (1) investigate emergency medical care priorities in Kosovo, (2)
      assess Kosovo's post-war development of emergency medical services and (3)
      identify expectations. METHODS: An instrument with seven open-ended questions,
      approved by the institutional review board, was designed for in-person interviews
      (preferred) or written survey. The survey was administered in October 2003 at the
      Kosovo University Clinical Center, Pristina, Kosovo, and one regional hospital.
      Targeted participants were emergency care providers, clinical consultants and
      health policy consultants. Surveys were conducted by interview with simultaneous
      interpretation by a native Albanian speaker, an orthopaedic surgeon or in written
      Albanian form. The responses were evaluated quantitatively and qualitatively.
      RESULTS: 13 respondents participated in the study: 10 gave interviews and 3
      provided written response; 7 were emergency care providers, 4 were emergency care
      consultants and 2 were health policy consultants. Emergency care priorities were
      defined as trauma, cardiac disease and suicide. Most respondents believed that
      emergency medicine as a specialised field was a post-war development. The
      international community was credited with the provision of infrastructure,
      supplies and training. Most respondents denied any harm from international
      assistance. However, some respondents described instances of inappropriate
      international investment. Ongoing needs are training of providers and equipping
      of facilities and vehicles. Improved hospital management, political
      administration and international involvement are thought to be necessary for
      continued development. CONCLUSIONS: Survey respondents agreed on priorities in
      emergency care, credited the international community with development to date,
      and identified administrative structures and international training support as
      the keys to ongoing development.

PMID- 17183037
TI  - Emergency blood transfusion services after the 2005 earthquake in Pakistan.
AB  - BACKGROUND: On 8 October 2005, an earthquake measuring 7.6 on the Richter Scale
      struck the Himalayan region of Kashmir and Hazara divisions, killing an estimated
      73,000 people. Soon after, a situation and response analysis of the emergency
      blood transfusion services was carried out in the affected areas to ascertain
      specific needs and suggest appropriate measures to assist in the disaster plan.
      METHOD: A semistructured questionnaire, complete with a checklist and
      participatory observation method, was used to collect data between 12 and 20
      October 2005. Study sites were Abbotabad, Mansehra and Muzzafarabad in Pakistan,
      and interviewees were surgeons and blood bank personnel. RESULTS: Of the seven
      major hospitals in the area, 3 (43%) had a functional blood transfusion service.
      Although supply of voluntary blood was abundant, shortage of individual blood
      groups was noted at each centre. Quality assurance standards were either non
      existent or inadequate. Only three blood banks had refrigerators, but with
      limited storage capacities. A complete breakdown of infrastructure coupled with
      frequent power failures posed a serious threat to safety of the blood. The
      continued aftershocks added to the problems. Although initial estimates of blood
      requirement were high, actual demand noted later was much lower. DISCUSSION:
      Timely establishment of blood banks in disaster areas, is a challenging task.
      Mobile blood banks can be advantageous in such situations. Organisation at a
      national level for blood transfusion services and development of a minimum
      standard of quality assurance in normal times should ensure safe emergency blood
      transfusion services when disaster strikes.

PMID- 17183038
TI  - The impacts and outcomes of implementing head injury guidelines: clinical
      experience in Thailand.
AB  - OBJECTIVE: To describe the impact of implementing clinical practice guidelines
      (CPG) for head injury in a trauma referral system in Songkla province, Thailand.
      METHODS: The CPG was developed by a local multidisciplinary team and implemented
      using multi-faceted methods. The outcome of patients with head injury from three
      community hospitals and a university hospital (Songklanagarind Hospital) was
      reported in terms of "talk and deteriorate" patients and a "poor" outcome for
      patients with severe head injury. Changes to clinical practice were observed
      where the guidelines were implemented. RESULTS: 1000 patients with head injury
      were enrolled from 1st August 2005 to 15th January 2006. The incidence of "talk
      and deteriorate" patients was 10.5% and a poor outcome was noted in 35.5% of
      patients with severe head injury, similar to the results of a previous study in
      Songklanagarind Hospital (p>0.05). Following implementation of the guidelines,
      19.8% of patients underwent CT scanning with similar outcomes for alert patients
      with and without basal skull fracture (p>0.05). The clinician-nurse relationship
      also improved and there was closer collaboration between hospitals. Short
      observation in community hospitals for repeat neurological examination may be an
      appropriate strategy for management of some patients with minor head injury.
      CONCLUSIONS: Local ownership, an appropriate implementation strategy and working
      as a multidisciplinary team are key factors for success in implementing the CPG.
      Basal skull fracture may not be an absolute criterion for CT imaging of the head.
      Further initiatives will be developed in response to the incidence of "talk and
      deteriorate" patients.

PMID- 17183039
TI  - Sick notes, general practitioners, emergency departments and fracture clinics.
AB  - BACKGROUND: General practitioner waiting times are increasing. The two national
      surveys regarding general practice showed that the number of patients waiting for
      >or=2 days for an appointment rose from 63% to 72% between 1998 and 2002, with
      25% waiting for >or=4 days. The Department of Health recognised that many
      patients discharged from hospitals and outpatient clinics required to visit their
      general practitioner for the sole purpose of obtaining a sick note. The report
      entitled Making a difference: reducing general practitioner paperwork estimated
      that 518 000 appointments (and 42 000 GP h) could be saved by ensuring that these
      patients were issued with a sick note directly from hospital rather than being
      referred to their general practitioner. This practice was to be adopted from July
      2001 and included patients discharged from wards as well as those seen in
      outpatient departments. METHOD: 50 emergency departments and fracture clinics in
      Scotland and England were contacted to assess whether these guidelines had been
      adopted. Only hospitals with both accident and emergency and fracture clinics
      were included; nurse-led and paediatric departments were excluded. RESULTS: Of
      the 25 Scottish emergency hospitals contacted, 4 (16%) accident and emergency
      departments and 8 (32%) fracture clinics issued sick notes. This was compared
      with 5 of 25 (20%) accident and emergency departments and 12 of 25 (48%) fracture
      clinics in England. Four Scottish and five English accident and emergency
      departments stated that it was policy to give sick notes, three Scottish and four
      English departments said that it was policy not to give them and the rest (72% in
      Scotland and 64% in England) stated that they had no clear policy but "just don't
      give them". CONCLUSION: The 2001 guidance from the joint Cabinet
      Office/Department of Health has not been fully incorporated into standard
      practice in Scotland and England. If all emergency departments and fracture
      clinics were to issue sick notes to patients requiring >7 days absence from work,
      this could reduce general practitioner consultations and improve waiting times.

PMID- 17183040
TI  - Delays in the treatment of cauda equina syndrome due to its variable clinical
      features in patients presenting to the emergency department.
AB  - OBJECTIVE: To identify reasons for delay in management of patients with cauda
      equina syndrome (CES) and to determine commonly presented features of CES.
      METHODS: Retrospectively, the presenting features and management of patients
      treated for CES over a 4-year period were reviewed. RESULTS: Reasons for delay in
      treatment were identified in over half of the patients. DISCUSSION: Most patients
      do not present with all the characteristic features of CES. Sacral sensory loss
      is a sensitive and relatively specific sign for diagnosing CES.

PMID- 17183041
TI  - Patients' perceptions of nasopharyngeal aspiration in the emergency department of
      a teaching hospital in Hong Kong.
AB  - Nasopharyngeal aspiration (NPA) is the preferred method for collecting specimens
      for viral culture in patients with respiratory tract infection. As virus
      identification may influence admission and treatment decisions, it is important
      to perform NPA in the emergency department. The test may be uncomfortable and
      poorly tolerated. This prospective study investigated patients' perceptions of
      NPA. Patients in the emergency department with upper respiratory tract infection
      undergoing NPA between 9 March 2005 and 12 August 2005 were included. 86 patients
      (mean (SD) age 47 (23) years; 49 women) were recruited. 22 (26%) patients
      complained that NPA was very uncomfortable, 59 (69%) reported that it was mildly
      uncomfortable and 5 (6%) patients reported no discomfort. On a 10-point scale,
      the median discomfort score was 4. 29 (34%) patients stated that NPA was more
      uncomfortable than blood taking, 19 (22%) patients felt that both were similar
      and 38 (44%) patients felt that NPA was less uncomfortable (p value not
      significant). NPA performed in the emergency department is well tolerated and
      should be considered in emergency departments when results may influence patient
      management.

PMID- 17183043
TI  - Critical care in the emergency department: patient transfer.

PMID- 17183044
TI  - Best evidence topic report. Use of Heliox in the management of acute exacerbation
      of COPD.

PMID- 17183046
TI  - Best evidence topic report. Is CT effective in cases of upper oesophageal fish
      bone ingestion?

PMID- 17183047
TI  - Best evidence topic report. Does plain radiography predict pneumothorax size?

PMID- 17183048
TI  - Best evidence topic report. Is defibrillation effective in accidental severe
      hypothermia in adults?

PMID- 17183049
TI  - The optimum reperfusion pathway for ST elevation acute myocardial infarction:
      development of a decision framework.
AB  - There is currently much debate about the relative roles of pharmacological
      reperfusion (ie, thrombolysis) and mechanical reperfusion (ie, primary
      percutaneous coronary intervention (PPCI) in the management of patients with
      acute ST segment elevation acute myocardial infarction (STEMI). Whilst the
      scientific debate is reaching some resolution in terms of appropriate
      interpretation of the evidence base, there are still significant resource issues
      within the UK that limit our ability to implement gold standard reperfusion
      therapy. Current evidence supports the use of one or other strategy in certain
      situations depending on various patient-related and logistical factors. This
      paper reviews the literature and builds the case for developing a strategic
      approach which includes both mechanical and pharmacological interventions,
      proposing that these are not mutually exclusive-indeed, that an approach which
      excludes one of these interventions will not be to the benefit of all patients.
      There is also a discussion of the role of rescue PPCI, facilitated PPCI and early
      post thrombolysis angiography in the management of STEMI. Cardiac networks
      throughout the UK are developing strategies to improve access to these
      interventions and this paper offers advice on the logical selection of
      interventions for reperfusion in the context of a clinical decision framework
      that is evidence-based, pragmatic and develops through a series of scenarios with
      increasing availability of resources. Four sequential scenarios are presented:
      the first to set the scene is largely consigned to history; the last, as of yet,
      is not robustly achievable within the UK, but represents the "optimum reperfusion
      pathway", to which most cardiac networks are striving. Most of us currently find
      ourselves in a period of change between the two and will relate to either
      scenario two or three.

PMID- 17183050
TI  - Cuffed endotracheal tube use in paediatric prehospital intubation: challenging
      the doctrine?
AB  - Questioning traditional doctrines is essential if patient care is to improve and
      progress. Historically accepted teaching is to use uncuffed tubes in all children
      up to puberty. This has been the practice in anaesthesia, intensive care and
      paediatric resuscitation both in and out of hospital. The use of cuffed
      endotracheal tubes (ETTs) in pre-pubertal children is evolving in general
      anaesthesia and intensive care in hospital practice. In contrast, uncuffed tubes
      are still widely recommended for use in the prehospital environment in this age
      group. There are a number of good reasons why a cuffed tube should be considered
      in preference to an uncuffed tube in children intubated out of hospital,
      regardless of their age or size. There are also some counterarguments which are
      worthy of consideration. This article presents the arguments for and against the
      use of cuffed tubes in children in prehospital care with a view to stimulating
      open discussion and debate.

PMID- 17183051
TI  - The experience of Teesside helicopter emergency services: doctors do not prolong
      prehospital on-scene times.
AB  - BACKGROUND: The benefits of helicopter emergency medical services (HEMSs)
      attending the severely injured have been documented in the past. The benefits of
      doctors attending HEMS casualties have been demonstrated in particular in inner
      urban and metropolitan areas. However, for UK regions with potentially less major
      trauma, concerns have been raised by ambulance services that a willingness of
      doctors to "stay and play" may lead to unnecessary delays on-scene without any
      additional benefit to the patient. AIMS: To identify factors that do prolong on
      scene time, establish whether doctors "stay and play" on-scene compared with
      paramedics and document how often advanced medical skills may have to be used by
      HEMS doctors working outside the London HEMS environment. METHODS: Patient report
      form data were studied with regard to the number of and mean on-scene times of
      missions flown to (A) road-traffic collisions (RTCs), (B) other trauma calls
      (OTCs) and (C) medical emergencies. Trauma missions (categories A and B) were
      further subcategorised with regard to associated patient entrapment. Any advanced
      medical interventions (AMIs) performed by HEMS doctors were recorded and
      categorised. Finally, we looked at the difference in on-scene times for physician
      paramedic partnerships (PPPs) and conventional paramedic crews (CPCs) for the
      above categories and subcategories. RESULTS: A total of 203 patient report forms
      were identified and examined. In all, 44.3% of missions were flown to RTCs with a
      further 44.3% for OTCs and 11.4% to medical emergencies. AMIs were performed by
      HEMS doctors in 34.1% of PPP missions, with a prehospital rapid sequence
      induction rate of 3.8%. Overall mean on-scene time was 25 min, with no difference
      for PPP and CPC missions. The mean on-scene time was prolonged by 6 min for RTCs
      (p = 0.006) and by 23 min for patient entrapment (p<0.001). No significant
      differences were found for the comparison between PPPs and CPCs in any of the
      subgroups A-C. However, there seemed to be a trend towards reduced on-scene times
      of PPPs for medical emergencies and patient entrapments. DISCUSSION: This study
      did not show any significant prolongation of mean on-scene times for PPP missions
      either overall or for any of the subgroups A-C. The fact that AMIs were performed
      in a large number of missions attended by HEMS doctors seems to further justify
      their current role in providing improved care at the roadside without leading to
      any delays in transfer to definitive care.

PMID- 17183052
TI  - Transient global amnesia caused by painless aortic dissection.
AB  - Neurological syndromes secondary to acute aortic dissection (AAD) are uncommon
      and usually consist of focal deficits after an embolic cerebral infarction. This
      article reports the observation of an AAD with the chief complaint of transient
      acute memory impairment-that is, a non-usual stroke-like symptom.

PMID- 17183053
TI  - Calcified cervical disc in a three year old.

PMID- 17183054
TI  - Acute laryngeal spasm.

PMID- 17183055
TI  - Intravascular haemolysis due to glucose-6-phosphate dehydrogenase deficiency in a
      patient with aluminium phosphide poisoning.

PMID- 17183056
TI  - The trauma room: a "one-stop shop" for diagnosis and treatment?

PMID- 17183057
TI  - Dictated versus hand-written accident and emergency discharge documents.

PMID- 17183058
TI  - Implementation of the sepsis resuscitation bundle: early experiences in a
      district general hospital.

PMID- 17183059
TI  - Sedate with caution.

PMID- 17183060
TI  - Preventing glass injuries in the emergency department.

PMID- 17183061
TI  - Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin,
      down-regulation of survivin and apoptosis in human colorectal cancer cells not
      expressing COX-2.
AB  - n-3 Polyunsaturated fatty acids have been shown to powerfully inhibit the growth
      of colon cancer cells, mainly acting as pro-apoptotic agents through inhibition
      of cycloxygenase-2 (COX-2) expression. Since dysregulation of beta-catenin
      expression is frequently found at early stage of colorectal carcinogenesis, we
      analyzed whether docosahexaenoic acid (DHA) may modify the expression of beta
      catenin in colon cancer cells (SW480 and HCT116) over-expressing this protein,
      but lacking COX-2. Futhermore, we investigated if alterations in beta-catenin
      expression may be associated with apoptosis induction. Treatment of cells with
      increasing concentrations of DHA induced a dose- and time-dependent inhibition of
      beta-catenin protein expression which, however, was not accompanied by
      modifications in beta-catenin transcription. Conversely, the proteasomal
      inhibitors MG132 and lactacystin prevented DHA-induced beta-catenin decrease,
      suggesting that DHA may regulate the proteasomal degradation of beta-catenin. The
      reduced levels of beta-catenin were accompanied by decreased translocation of
      beta-catenin into the nucleus, where it acts as a transcription factor in concert
      with T-Cell Factor (TCF). DHA, at the same range of concentrations, was also able
      to induce apoptosis by a caspase-3-dependent mechanism and to cause a dose- and
      time-dependent decrease of survivin, an apoptosis inhibitor undetectable in
      normal tissues and expressed in colorectal cancer through TCF-beta-catenin
      stimulation. Several other proteins regulated by the TCF-beta-catenin pathway and
      involved in regulation of tumor growth were down-regulated by DHA, including
      peroxisome proliferator-activated receptor-delta, membrane type 1 (MT1)-matrix
      metalloproteinase (MMP), MMP-7 and vascular endothelial growth factor. The
      present study, thus, raises the possibility that DHA may exert pro-apoptotic and
      antitumoral effects through proteasomal regulation of beta-catenin levels and
      alterations in the expression of TCF-beta-catenin target genes.

PMID- 17183062
TI  - The molecular epidemiology of lung cancer.
AB  - Lung cancer is the leading cause of cancer mortality worldwide. There have been
      only slight improvements in early diagnosis and survival, reflecting limited
      advances in screening and treatment for lung cancer. The identification of host
      differences in susceptibility to lung carcinogens, in particular to cigarette
      smoke, is essential in predicting who is at highest risk. Susceptibility
      differences in the form of rare, high-penetrance genes are suggested from studies
      of familial aggregation of lung cancer and a linkage study. Studies focused on
      more common, low-penetrance genes in the tobacco smoke metabolism pathways (phase
      I and phase II enzymes) and DNA repair pathways are reviewed, as are inflammation
      and cell cycle-related genes and DNA adducts as intermediate biomarkers. Also
      reviewed are studies of epigenetic mechanisms, such as methylation, as
      alternative sources of variation in host susceptibility. Studies of molecular
      epidemiology in lung cancer survival are discussed briefly. In the future,
      studies that focus on complex interactions between multiple genes and
      environmental exposures within pertinent pathways are needed. New technological
      advances in genotyping will help move the field forward.

PMID- 17183063
TI  - Green tea and the prevention of breast cancer: a case-control study in Southeast
      China.
AB  - Breast cancer is the most common malignancy in women worldwide. Tea has
      anticarcinogenic effects against breast cancer in experimental studies. However,
      epidemiologic evidence that tea protects against breast cancer has been
      inconsistent. A case-control study was conducted in Southeast China between 2004
      and 2005. The incidence cases were 1009 female patients aged 20-87 years with
      histologically confirmed breast cancer. The 1009 age-matched controls were
      healthy women randomly recruited from breast disease clinics. Information on
      duration, frequency, quantity, preparation, type of tea consumption, diet and
      lifestyle were collected by face-to-face interview using a validated and reliable
      questionnaire. Conditional logistic regression analyses were used to estimate
      odds ratios (ORs) and associated 95% confidence intervals. Compared with non-tea
      drinkers, green tea drinkers tended to reside in urban, have better education and
      have higher consumption of coffee, alcohol, soy, vegetables and fruits. After
      adjusting established and potential confounders, green tea consumption was
      associated with a reduced risk of breast cancer. The ORs were 0.87 (0.73-1.04) in
      women consuming 1-249 g of dried green tea leaves per annum, 0.68 (0.54-0.86) for
      250-499 g per annum, 0.59 (0.45-0.77) for 500-749 g per annum and 0.61 (0.48
      0.78) for >or=750 g per annum, with a statistically significant test for trend (P
      < 0.001). Similar dose-response relationships were observed for duration of
      drinking green tea, number of cups consumed and new batches prepared per day. We
      conclude that regular consumption of green tea can protect against breast cancer.
      More research to closely examine the relationship between tea consumption and
      breast cancer risk is warranted.

PMID- 17183064
TI  - Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand
      mediated apoptosis through downregulation of ERK and Akt in lung adenocarcinoma
      A549 cells.
AB  - The cytotoxic effect of the tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) is limited in some cancer cells, including A549 lung
      adenocarcinoma cells. However, treatment with TRAIL in combination with subtoxic
      concentrations of sulforaphane (SFN) sensitizes TRAIL-resistant A549 cells to
      TRAIL-mediated apoptosis. Combined treatment with SFN and TRAIL induced chromatin
      condensation, DNA fragmentation, annexin V staining and sub-G(1) phase DNA
      content. These indicators of apoptosis correlate with the induction of caspase-3
      activity that results in the cleavage of poly(ADP-ribose) polymerase and the
      release of lactate dehydrogenase. Both the cytotoxic effect and apoptotic
      characteristics induced by combined treatment were significantly inhibited by z
      DEVD-fmk, a caspase-3 inhibitor, demonstrating the important role of caspase-3 in
      the observed cytotoxic effect. Combined treatment also triggered the activation
      of p38 MAPK and JNK, and downregulation of ERK and Akt. Inhibitors of ERK
      (PD98059) or Akt (LY294002), but not p38 MAPK, resulted in significantly
      decreased cell viability. Although the activation of JNK was increased in
      response to combined treatment, inhibition of the JNK pathway significantly
      attenuated cell viability. These results indicate that caspase-3 is a key
      regulator of apoptosis in response to combined SFN and TRAIL in human lung
      adenocarcinoma A549 cells through downregulation of ERK and Akt.

PMID- 17183065
TI  - Functional polymorphisms in FAS and FASL contribute to increased apoptosis of
      tumor infiltration lymphocytes and risk of breast cancer.
AB  - The FAS-FASL system plays crucial role in counterattack of cancer cell against
      immune system. This study examined the effects of FAS (-1377G/A and -670A/G) and
      FASL (-844T/C and 7896G/C) polymorphisms on breast cancer risk and apoptosis of T
      lymphocytes. The effect on breast cancer risk was determined by case-control
      analysis of 840 patients and 840 controls. The effects on T-lymphocyte apoptosis
      were determined by activation-induced cell death (AICD) of T cells ex vivo and by
      analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer
      tissue. We found moderately increased risk associated with FAS -1377AG [odds
      ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.59] and -1377AA (OR, 1.36;
      95% CI, 1.01-1.82) genotypes compared with the -1377GG genotype and decreased
      risk associated with FASL -844CT (OR, 0.76; 95% CI, 0.62-0.94) and -844TT (OR,
      0.66; 95% CI, 0.43-1.00) genotypes compared with the -844CC genotype. T
      lymphocytes with the FASL -844CC genotype had heightened FASL expression that is
      associated with increased AICD of the T cells stimulated by MCF-7 cells or
      phytohemagglutinin compared with the FASL -844TT genotype (10.38 +/- 4.09% and
      24.29 +/- 1.50% versus 6.03 +/- 0.41% and 17.96 +/- 3.66%; P < 0.05 and 0.001).
      Breast cancer patients with the FASL -844CC genotype had higher apoptotic TILs in
      their cancer tissues than those with the FASL -844TT genotype (33.7 +/- 1.2%
      versus 19.1 +/- 2.0%; P = 0.007). These findings indicate that functional
      polymorphisms in FAS and FASL contribute to increased apoptosis of tumor
      infiltration lymphocytes and risk of breast cancer.

PMID- 17183066
TI  - Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice.
AB  - The farnesoid X receptor (FXR) controls the synthesis and transport of bile acids
      (BAs). Mice lacking expression of FXR, designated Fxr-null, have elevated levels
      of serum and hepatic BAs and an increase in BA pool size. Surprisingly, at 12
      months of age, male and female Fxr-null mice had a high incidence of degenerative
      hepatic lesions, altered cell foci and liver tumors including hepatocellular
      adenoma, carcinoma and hepatocholangiocellular carcinoma, the latter of which is
      rarely observed in mice. At 3 months, Fxr-null mice had increased expression of
      the proinflammatory cytokine IL-1beta mRNA and elevated beta-catenin and its
      target gene c-myc. They also had increased cell proliferation as revealed by
      increased PCNA mRNA and BrdU incorporation. These studies reveal a potential role
      for FXR and BAs in hepatocarcinogenesis.

PMID- 17183067
TI  - A novel synthetic analogue of a constituent of Isodon excisus inhibits
      transcription of CYP1A1, -1A2 and -1B1 by preventing activation of the aryl
      hydrocarbon receptor.
AB  - We investigated the effect of a novel synthetic analogue of a constituent from
      the Chinese medicinal herb Isodon excisus, 3-(3-methoxy-phenyl)-N-(3, 4, 5
      trimethoxy-phenyl)-acrylamide (compound 343), on the carcinogen activation
      pathway mediated by the aryl hydrocarbon receptor (AhR) in human hepatoma HepG2
      cells. We found that compound 343 inhibited the upregulation of cytochrome P-450
      (CYP) enzyme activity in cells treated with the AhR ligands and potent
      carcinogens, dimethylbenz[a]anthracene (DMBA) or 2, 3, 7, 8-tetrachlorodibenzo-p
      dioxin (TCDD). Compound 343 also inhibited the DMBA- or TCDD-induced increase in
      CYP1A1, -1A2 and -1B1 mRNA levels. Carcinogen-induced transcription of CYP genes
      was also suppressed by compound 343, as measured by a reporter gene controlled by
      the xenobiotic-responsive element (XRE). This was confirmed by measuring the
      amount of carcinogen-induced CYP1A1 heterogeneous nuclear RNA. Compound 343
      blocked the DMBA- or TCDD-induced activation of the AhR DNA-binding capacity for
      the XRE, as measured by a chromatin immunoprecipitation assay. Compound 343 also
      inhibited CYP enzyme activity in microsomes isolated from DMBA- or TCDD-treated
      cells, as well as the activity of recombinant CYP1A1, -1A2 and -1B1, indicating
      that compound 343 directly inhibits CYP enzymes. These results indicate that
      compound 343 is both a potent inhibitor of carcinogen-induced CYP enzyme
      expression, as well as a direct inhibitor of CYP enzymes.

PMID- 17183068
TI  - Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic
      target in human esophageal squamous cell carcinoma.
AB  - Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for
      tumorigenicity and progression of many tumors but this pathway has not been well
      studied as a prognostic factor or potential therapeutic target in esophageal
      squamous cell carcinoma (ESCC). In this paper, the association between the
      expression of IGF-Ir and IGF-II ligand and prognosis was investigated
      immunohistochemically in 100 surgically resected ESCC. We then assessed the
      therapeutic effect of blocking IGF receptor signaling using dominant negative IGF
      Ir (IGF-Ir/dn) in ESCC in vitro. Expression of IGF-Ir and IGF-II were detected in
      60 and 50% of tumors, respectively, and were associated with invasion depth,
      metastasis, advanced tumor stage and recurrence. Patients with tumors expressing
      both IGF-Ir and IGF-II had a significantly shorter survival than those expressing
      either alone or neither in both single and multivariate analysis. IGF-Ir/dn
      suppressed proliferation and motility as well as upregulating chemotherapy
      induced apoptosis through blocking ligand-induced Akt activation. We propose that
      detection of IGF-Ir/IGF-II in ESCC may be useful for the prediction of recurrence
      and poor prognosis and for selecting patients for IGF-Ir-targeted therapy.
      Therapeutic blockade of IGF-Ir may be a useful anticancer therapeutic for ESCC.

PMID- 17183069
TI  - Genetic and epigenetic profiling in early colorectal tumors and prediction of
      invasive potential in pT1 (early invasive) colorectal cancers.
AB  - Morphologically, early colorectal tumors are divided into two groups, protruded
      type tumors and flat-type tumors. Although some studies have shown genetic
      alterations in protruded-type tumors, little is known about genetic and
      epigenetic alterations in flat-type tumors, as well as pT1 (early invasive)
      colorectal cancers (CRCs). In the current study, we compared the frequencies of
      genetic and epigenetic alterations of the RAS-RAF and Wnt signaling pathways in
      flat-type and protruded-type tumors. In addition, we investigated the
      relationship between those alterations and invasive potential of pT1 CRCs.
      Methylations of RASSF2, O-6-methylguanine-DNA methyltransferase (MGMT), Wnt
      inhibitory factor-1 (WIF-1), EPHB2, CDKN2A and MLH1 were detected in 44.3, 30.3,
      81.4, 7.5, 43.6 and 13.4% of the 307 early colorectal tumors, respectively.
      Mutations of KRAS, BRAF, catalytic subunit alpha of phosphatidylinositol 3'
      kinase (PIK3CA) and beta-catenin were detected in 25.4, 4.6, 1.6 and 9.4% of
      those tumors, respectively. Methylations of MGMT, WIF-1 and CDKN2A were detected
      in significantly higher percentages of protruded-type tumors than in flat-type
      tumors. Mutation of at least one gene was detected in a significantly higher
      percentage of flat-type tumors than in protruded-type tumors. RASSF2 methylation
      was correlated significantly with KRAS, BRAF or PIK3CA mutation. Multiple
      logistic analysis showed that lymphatic invasion and RASSF2 methylation with
      KRAS, BRAF or PIK3CA mutation were independent risk factors for venous invasion
      in pT1 CRCs. In conclusion, since genetic alterations of these pathways have
      frequently occurred in flat-type tumors, flat-type tumors seem to have a distinct
      genetic profile different from that of protruded-type tumors. RASSF2 methylation
      with oncogenic activation is a promising biomarker for predicting invasive
      potential of pT1 CRCs.

PMID- 17183070
TI  - Influence of calcium and phosphorus, lactose, and salt-to-moisture ratio on
      cheddar cheese quality: pH changes during ripening.
AB  - The pH of cheese is an important attribute that influences its quality.
      Substantial changes in cheese pH are often observed during ripening. A combined
      effect of calcium, phosphorus, residual lactose, and salt-to-moisture ratio (S/M)
      of the cheese on the changes in cheese pH during ripening was investigated. Eight
      cheeses with 2 levels of Ca and P (0.67 and 0.47% vs. 0.53 and 0.39%,
      respectively), lactose at pressing (2.4 vs. 0.78%), and S/M (6.4 vs. 4.8%) were
      manufactured. All the cheeses were salted at a pH of 5.4, pressed for 5 h, and
      then ripened at 6 to 8 degrees C. The pH of the salted curds before pressing and
      the cheeses during 48 wk of ripening was measured. Also, cheeses were analyzed
      for water-soluble Ca and P, organic P, and bound inorganic P during ripening.
      Changes in organic acids' concentration and shifts in the distribution of Ca and
      P between different forms were studied in relation to changes in pH. Cheeses with
      low S/M exhibited a larger increase in acid production during ripening compared
      with high S/M cheeses. Cheeses with the highest concentration of bound inorganic
      P exhibited the highest pH, whereas cheeses with the lowest concentration of
      bound inorganic P exhibited the lowest pH among the 8 treatments. Although
      conversion of lactose to short-chain, water-soluble organic acids decreased
      cheese pH, bound inorganic phosphate buffered the changes in cheese pH.
      Production of acid in excess of the buffering capacity (which was the case in low
      Ca and P and low S/M treatments) led to a low pH, whereas solubilization of bound
      inorganic P in excess to acid production (which was the case in high Ca and P and
      high S/M treatments) led to an increase in pH. However, for cheeses with high Ca
      and P and low S/M, changes in cheese pH were influenced by the level of residual
      lactose. Hence, pH changes in Cheddar cheese can be modulated by a concomitant
      control on the amount and state of Ca and P, level of residual lactose, and S/M
      of the cheese.

PMID- 17183071
TI  - Effects of ultra-high pressure homogenization on the cheese-making properties of
      milk.
AB  - The effects of single- or 2-stage ultra-high pressure homogenization (UHPH; 100
      to 330 MPa) at an inlet temperature of 30 degrees C on the cheese-making
      properties of bovine milk were investigated. Effects were compared with those
      from raw, heat-pasteurized (72 degrees C for 15 s), and conventional homogenized
      pasteurized (15 + 3 MPa, 72 degrees C for 15 s) treatments. Rennet coagulation
      time, rate of curd firming, curd firmness, wet yield, and moisture content of
      curds were assessed. Results of particle size and distribution of milk, whey
      composition, and gel microstructure observed by confocal laser scanning
      microscopy were analyzed to understand the effect of UHPH. Single-stage UHPH at
      200 and 300 MPa enhanced rennet coagulation properties. However, these properties
      were negatively affected by the use of the UHPH secondary stage. Increasing the
      pressure led to higher yields and moisture content of curds. The improvement in
      the cheese-making properties of milk by UHPH could be explained by changes to the
      protein-fat structures due to the combined effect of heat and homogenization.

PMID- 17183072
TI  - Application of fluorescence spectroscopy for monitoring changes in nonfat dry
      milk during storage.
AB  - The objective of this study was to determine if fluorescence spectroscopy could
      be used to characterize the biochemical characteristics of nonfat dry milk (NDM)
      caused by manufacturing and storage conditions. Nine low-heat NDM samples were
      collected from 3 manufacturers and stored at 4 temperatures (4, 22, 35, and 50
      degrees C) for 8 wk. The spectra of Maillard products, tryptophan, and riboflavin
      were recorded and analyzed with principal components analysis. Colorimetric
      indices L*, a*, and b* were also determined. The before-storage NDM samples
      collected from each manufacturer had different fluorescent characteristics.
      Inconsistency was observed for the NDM samples collected from 1 manufacturer,
      whereas the samples from the other 2 manufacturers displayed consistent
      fluorescence characteristics. Biochemical reactions, such as Maillard reaction,
      modification of the tryptophan environment, and degradation of riboflavin
      occurred during the manufacturing process. For each of the data collections,
      discrimination of the NDM samples stored at 50 degrees C from the samples stored
      at 4, 22, and 35 degrees C was observed in the similarity maps. The factor
      loadings of the first 2 principal components for the fluorescence spectra of the
      samples before storage were similar to the principal components analysis results
      of the samples during storage. It appears that similar factors are responsible
      for the variation in the samples before storage and their changes during storage.
      Additionally, storage of the samples at 50 degrees C accelerated these reactions.
      The results demonstrate that front-face fluorescence spectroscopy, coupled with
      multivariate statistical methods, can be utilized as an analytical technique to
      monitor variation in NDM samples from different manufacturers and changes during
      storage.

PMID- 17183073
TI  - Lactoferrin and immunoglobulin contents in camel's milk (Camelus bactrianus,
      Camelus dromedarius, and Hybrids) from Kazakhstan.
AB  - Lactoferrin (Lf) and IgG were estimated in camel's milk from Kazakhstan, where 2
      species of camels (Camelus bactrianus, Camelus dromedarius) and their hybrids
      cohabit. The concentrations of Lf and IgG were determined according to 3
      variation factors: region (n = 4), season (n = 4), and species (n = 5; sample 4
      was mixed milk and sample 5 was of unknown origin). The mean values in raw
      camel's milk were 0.229 +/- 0.135 mg/mL for Lf concentration and 0.718 +/- 0.330
      mg/mL for IgG concentration. The seasonal effect was the only significant
      variation factor observed, with the highest values in the spring for Lf and in
      the winter for IgG. The Lf concentration varied in 1-wk postpartum milk from
      1.422 to 0.586 mg/mL. The range in IgG concentration was wide and decreased from
      132 to 4.75 mg/mL throughout the 7 d postpartum, with an important drop after
      parturition. In fermented milk, the lactoproteins are generally hydrolyzed. For
      milk samples from undefined species, discriminant analyses did not allow the
      origin of the species to be determined. A slight correlation between Lf and IgG
      concentrations was observed in raw milk. The values were slightly higher than
      those reported in cow's milk, but this difference was insufficient to attribute
      medicinal virtues to camel's milk.

PMID- 17183074
TI  - Lipolysis in cheddar cheese made from raw, thermized, and pasteurized milks.
AB  - The evolution of free fatty acids (FFA) was monitored over 168 d of ripening in
      Cheddar cheeses manufactured from good quality raw milk (RM), thermized milk (TM;
      65 degrees C x 15 s), and pasteurized milk (PM; 72 degrees C x 15 s). Heat
      treatment of the milk reduced the level and diversity of raw milk microflora and
      extensively or wholly inactivated lipoprotein lipase (LPL) activity. Indigenous
      milk enzymes or proteases from RM microflora influenced secondary proteolysis in
      TM and RM cheeses. Differences in FFA in the RM, TM, and PM influenced the levels
      of FFA in the subsequent cheeses at 1 d, despite significant losses of FFA to the
      whey during manufacture. Starter esterases appear to be the main contributors of
      lipolysis in all cheeses, with LPL contributing during production and ripening in
      RM and, to a lesser extent, in TM cheeses. Indigenous milk microflora and
      nonstarter lactic acid bacteria appear to have a minor contribution to lipolysis
      particularly in PM cheeses. Lipolytic activity of starter esterases, LPL, and
      indigenous raw milk microflora appeared to be limited by substrate accessibility
      or environmental conditions over ripening.

PMID- 17183075
TI  - The formation of calcium lactate crystals is responsible for concentrated acid
      whey thickening.
AB  - The use of spray drying for dehydration of acid whey is generally limited by the
      appearance of uncontrolled thickening and solidifying of the whey mass during the
      lactose crystallization step. The origin of this physical change is still unknown
      and probably linked to complex interactions between physical properties and
      chemical composition of these products. To understand this phenomenon, we
      simulated the thickening of concentrated acid whey on a laboratory scale by
      measuring the flow resistance changes as a function of time and whey composition.
      The thickening process was characterized by an amplitude of torque and a lag time
      (induction time). Thickening of lactic acid whey concentrate occurred regardless
      of the presence of whey proteins or lactose crystals. Moreover, this work clearly
      demonstrated that the thickening process was due to the formation of filamentous
      structures corresponding to calcium lactate crystals and showed a large
      dependence on calcium and lactate contents, pH, and phosphate concentration.

PMID- 17183076
TI  - Inhibitory activities of bovine macromolecular whey proteins on rotavirus
      infections in vitro and in vivo.
AB  - Rotavirus is a major cause of infantile viral gastroenteritis and can lead to
      severe and sometimes lethal dehydration. Previous studies have shown that breast
      fed children are better protected against symptomatic infections, and that the
      milk fat globule protein lactadherin might be at least partly responsible for
      this effect. In vitro studies have shown that human lactadherin, in contrast to
      the bovine ortholog, could inhibit rotavirus infectivity, and that bovine MUC1
      and a commercially available bovine macromolecular whey protein (MMWP) fraction
      proved to be effective. The present work describes the versatility of MMWP
      against the infection of 2 human intestinal cell lines (Caco-2 and FHs 74 Int) by
      4 different rotavirus strains (Wa, RRV, YM, RF). Isolation of a protein fraction
      (CM3Q3) from MMWP that effectively inhibits rotavirus infectivity in vitro is
      documented. Purification was achieved by monitoring the rotaviral inhibitory
      activity in fractions obtained from 2 consecutive steps of ion-exchange
      chromatography. The major component of CM3Q3 was shown to be bovine IgG, and the
      attenuating capacity of this fraction is most properly linked to this component.
      The capacity of MMWP, MUC1, lactadherin, and the CM3Q3 fraction to inhibit the
      infectivity of the murine EMcN rotavirus strain was analyzed in adult BALB/c mice
      by using 2 different amounts of virus (10 and 100 times more than 50% the viral
      shedding doses). Only CM3Q3 was able to significantly affect the shedding of
      rotavirus in the stools of experimentally infected mice when the high viral dose
      was given. Detection of rotavirus-specific serum antibodies showed that the high
      dose infected all groups of mice. Experiments with the low dose of virus implied
      that all the tested milk proteins could affect the viral shedding in stools; in
      addition, use of MUC1, MMWP, and CM3Q3 prevented the appearance of serum viral
      antibodies. The advantages of using bovine immunoglobulins to induce passive
      immunity against rotavirus have been substantially investigated, although studies
      have mainly focused on the use of derivatives from immunized cows, especially
      colostrum. This report associates considerable activity against rotavirus
      infectivity with an ordinary whey product, suggesting that there might be
      alternatives to colostral-derived products.

PMID- 17183077
TI  - Evidence for fibril-like structure in bovine casein micelles.
AB  - The addition of Congo red (CR) dye to diluted raw skim milk resulted in a red
      shift indicative of the presence of fibril-like structures. Thioflavin T (ThT) is
      another dye that very specifically binds to protein fibrils, and when added to
      undiluted raw skim milk, the classic 485 nm fluorescence peak of a ThT-fibril
      complex was observed. Repeating these experiments with various raw milk
      components showed that the CR red shift and ThT fluorescence peak were due to the
      presence of casein micelles, and to a lesser extent, sodium caseinate.
      Fluorescent peaks were also observed when ThT was added to solutions of purified
      alpha(S)- and kappa-casein, but not beta-casein, in 0.5 M HEPES buffer (pH =
      6.8). The addition of 25 mM Ca(2+) had no effect on beta-casein fluorescence, and
      significantly reduced the kappacasein peak. However, adding 25 mM Ca(2+) to
      alpha(S)-casein produced a turbid solution and a 6-fold increase in fluorescence,
      indicating that the aggregates formed contain fibril-like structure. Casein
      micelle images obtained by transmission electron microscopy showed the presence
      of short (7 to 10 nm) fibers cross-linked by dense aggregate junction zones. The
      observed fibers closely resemble protofibrils, intermediate structures that are
      observed during the formation of amyloid fibrils.

PMID- 17183078
TI  - Characteristics of reduced fat milks as influenced by the incorporation of folic
      acid.
AB  - Folic acid plays an important role in the prevention of neural tube defects
      (e.g., spina bifida and anencephaly), heart defects, facial clefts, urinary
      abnormalities, and limb deficiencies. Milk and milk products serve as a potential
      source for folic acid fortification because of the presence of folate-binding
      proteins that seem to be involved in folate bioavailability. Although milk is not
      a good source of folic acid, fortification could help in the prevention of the
      above-mentioned defects. The objective of this study was to examine the
      physicochemical characteristics of reduced fat milks fortified with folic acid.
      Reduced fat milks were prepared using 25, 50, 75, and 100% of the recommended
      dietary allowance of 400 microg of folic acid. Treatments included addition of
      folic acid at these levels before and after pasteurization. Color, pH, fat,
      protein, viscosity, folic acid concentration, folate-binding protein
      concentration, folate-binding protein profile, standard plate count, and coliform
      counts were determined on d 1, 7, 14, and 21. A consumer acceptability test was
      conducted on d 7. Data from the consumer panel were analyzed using ANOVA (PROC
      GLM) with means separation to determine the differences among treatments. Data
      obtained from the color, pH, fat, protein, viscosity, folic acid concentration,
      folate-binding protein concentration, standard plate count, and coliform counts
      were analyzed using the GLM with a repeated measure in time. Significant
      differences were determined at P < 0.05 using Tukey's Studentized Range Test.
      There were no differences in the electrophoretic mobility of folate-binding
      protein in the samples. The concentration of folic acid was significantly higher
      in reduced fat milks fortified with folic acid after pasteurization compared with
      the treatments in which folic acid was added before pasteurization. The consumer
      panelists did not find any significant differences in flavor, appearance, or
      texture of folic acid fortified reduced fat milks compared with that of the
      control. Fortification of reduced fat milks with folic acid can be accomplished
      without adversely affecting the product characteristics.

PMID- 17183079
TI  - Response of two Salmonella enterica strains inoculated in model cheese treated
      with high hydrostatic pressure.
AB  - The aim of this work was to determine the response to high hydrostatic pressure
      and the ability for survival, recovery, and growth of 2 strains of Salmonella
      enterica (Salmonella enteritidis and Salmonella typhimurium) inoculated in a
      washed-curd model cheese produced with and without starter culture. Inoculated
      samples were treated at 300 and 400 MPa for 10 min at room temperature and
      analyzed after treatment and after 1, 7, and 15 d of storage at 12 degrees C to
      study the behavior of the Salmonella population. Cheese samples produced with
      starter culture and treated at 300 and 400 MPa showed maximum lethality; no
      significant differences in the baroresistant behavior of both strains were
      detected. Nevertheless, when starter culture was not present, the maximum
      lethality was only observed in cheese samples treated at 400 MPa, in the case of
      S. enteritidis. Ability to repair and grow was not observed in model cheese
      produced with starter culture and cell counts of treated samples decreased after
      15 d of storage at 12 degrees C. In cheese produced without starter culture,
      Salmonella cells showed the ability to repair and grow during the storage period,
      reaching counts over 3 log(10) (cfu/mL) in both applied treatments and serotypes.
      These results suggest that high hydrostatic pressure treatments are effective to
      reduce Salmonella population in this type of cheese, but the presence of the
      starter culture affects the ability of this microorganism to repair and grow
      during the storage period.

PMID- 17183080
TI  - Effect of protein-to-fat ratio of milk on the composition, manufacturing
      efficiency, and yield of cheddar cheese.
AB  - Twenty-three Cheddar cheeses were prepared from milks with a protein content of
      3.66% (wt/wt) and with different protein-to-fat ratio (PFR) in the range 0.70 to
      1.15; the PFR of each milk differed by 0.02. For statistical analysis, the 23
      cheeses were divided into 3 PFR groups: low (LPFR; 0.70 to 0.85), medium (MPFR;
      0.88 to 1.00) and high (HPFR; 1.01 to 1.15), which were compared using ANOVA. The
      numbers of PFR values in the LPFR, MPFR, and HPFR groups were 9, 7, and 7,
      respectively. Data were also analyzed by linear regression analysis to establish
      potentially significant relationships among the PFR and response variables.
      Increasing PFR significantly increased the levels of cheese moisture, protein,
      Ca, and P, but significantly reduced the levels of moisture in nonfat substances,
      fat-in-DM, and salt-in-moisture. The percentage of milk fat recovered in the LPFR
      cheese was significantly lower than that in the MPFR or HPFR cheeses. In
      contrast, the recovery of water from milk to the LPFR cheese was significantly
      higher than that in the MPFR or HPFR cheeses. Increasing the PFR led to a
      significant decrease in the actual yield of cheese per 100 kg of milk but a
      significant increase occurred in the normalized yield of cheese per 100 kg of
      milk with reference values of fat plus protein (3.4 and 3.3%, wt/wt,
      respectively). The results demonstrate that alteration of the PFR of cheese milk
      in the range 0.70 to 1.15 has marked effects on cheese composition, component
      recoveries, and cheese yield.

PMID- 17183081
TI  - Effects of high pressure treatment on volatile profile during ripening of ewe
      milk cheese.
AB  - The effect of high-pressure treatment on the volatile profile of ewe milk cheeses
      was investigated. Cheeses were submitted to 200, 300, 400 and 500 MPa at 2 stages
      of ripening (after 1 and 15 d of manufacturing) and volatile compounds were
      assayed at 15 and 60 d of ripening. High-pressure treatment altered the balance
      of volatile profile of cheeses, limiting the formation of acids, alcohols,
      ketones, aldehydes, and sulfur compounds and enhancing the formation of 2,3
      butanedione. In general, cheeses pressurized at 15 d of ripening were more
      similar to untreated cheeses than those treated at 1 d. Cheeses treated at 300
      MPa after 1 d of manufacturing were characterized by higher levels of free amino
      acids, ethanol, ethyl esters, and branched-chain aldehydes, whereas cheeses
      treated at 500 MPa after 1 d of manufacturing had lower microbial populations,
      showed the highest abundance of 2,3-butanedione, pyruvaldehyde, and methyl
      ketones, and the lowest abundance of alcohols.

PMID- 17183082
TI  - Effects of feeding fish meal and n-3 fatty acids on milk yield and metabolic
      responses in early lactating dairy cows.
AB  - The study was designed to test the effects of feeding fish meal (FM) and specific
      n-3 fatty acids on milk yield and composition, dry matter intake, plasma
      concentrations of metabolic hormones and metabolites, and liver triglyceride
      accumulation in early lactating cows. From 5 to 50 d in milk (DIM), cows were fed
      diets that were isonitrogenous, isoenergetic, and isolipidic containing none
      (control), 1.25, 2.5, or 5% menhaden FM or 2.3% Ca salts of fish oil fatty acids
      (CaFOFA). Milk yield (48.2, 49.8, 48.6, 53.5, and 52.2 +/- 1.0 kg/d,
      respectively) and dry matter intake (22.7, 22.8, 23.0, 23.8, and 24.7 +/- 0.5
      kg/d, respectively) differed among diets. Average daily plasma glucose
      concentration (53.4, 55.3, 51.1, 57.6, and 57.3 +/- 1.3 mg/dL, respectively) was
      also affected by diet, and plasma insulin concentration was increased by 5% FM
      and 2.3% Ca-FOFA. At 25 and 50 DIM, blood was collected before feeding and hourly
      for 11 h after feeding. Plasma glucose concentrations in cows during the day were
      similar among diets at 25 DIM, but differed at 50 DIM (54.6, 54.4, 52.4, 60.5,
      and 58.3 +/- 1.4 mg/dL for 0, 1.25, 2.5, and 5% FM or 2.3% CaFOFA, respectively).
      Plasma insulin was increased in cows fed 5% FM and 2.3% CaFOFA at 25 DIM and was
      similar among diets at 50 DIM. Dietary treatments had no significant effect on
      milk composition, energy balance, or on daily plasma concentrations of
      nonesterified fatty acids, beta-hydroxybutyrate, and urea. Plasma aspartate
      aminotransferase and hepatic triglyceride concentration in cows did not differ
      among diets at 21 DIM. Results from this experiment demonstrate that dietary
      supplementation with FM or n-3 polyunsaturated fatty acids in early lactating
      dairy cows significantly increased milk yield and DMI with no change in milk
      composition.

PMID- 17183083
TI  - Effects of feeding fish meal and n-3 fatty acids on ovarian and uterine responses
      in early lactating dairy cows.
AB  - The study was designed to test the effects of dietary supplementation with fish
      meal or specific n-3 fatty acids on ovarian activity and uterine responses in
      early lactating cows. From 5 to 50 d in milk (DIM), cows were fed diets that were
      isonitrogenous, isoenergetic, and isolipidic containing none (control), 1.25,
      2.5, or 5% menhaden fish meal (FM) or 2.3% Ca salts of fish oil fatty acids
      (CaFOFA). Ovarian follicular dynamics were monitored along with plasma
      concentrations of estradiol and progesterone. Beginning at 23 DIM, cows were
      induced into a synchronized ovulatory cycle. On d 15 after ovulation (49 DIM),
      cows were injected with oxytocin and blood samples were collected to monitor
      uterine release of PGF(2alpha) (measured as 13, 14-dihydro-15-keto PGF(2alpha);
      PGFM). Uterine endometrial biopsies were collected for fatty acid analysis and
      cyclooxygenase-2 (COX-2) protein measurement. Ovarian follicular activities as
      well as plasma estradiol and progesterone concentrations were similar across
      diets. Endometrial fatty acid composition of eicosapentaenoic acid (C20:5, n-3)
      and docosahexaenoic acid (C22:6, n-3) were increased as much as 3-fold by
      supplementation with fish meal and CaFOFA. Conjugated linoleic acid (C18:2 cis-9,
      trans-11) in the endometrium was also increased; conversely, arachidonic acid
      (C20:4, n-6) percentage was decreased by 5% FM. Plasma PGFM response to oxytocin
      injection was not different among diets and endometrial COX-2 protein abundance
      did not differ. Results from this experiment demonstrate that dietary
      supplementation with fish meal or n-3 fatty acids in early lactating dairy cows
      significantly increased uterine n-3 fatty acid concentrations, but had no
      apparent effect on endometrial COX-2 or PGF(2alpha) production in response to
      oxytocin challenge.

PMID- 17183084
TI  - Prolactin-induced activation of nuclear factor kappaB in bovine mammary
      epithelial cells: role in chronic mastitis.
AB  - We sought to determine whether prolactin (PRL) could influence the neutrophilic
      inflammation that characterizes chronic mastitis. Most of the genes encoding
      inflammatory proteins depend on the nuclear factor kappaB (NF-kappaB) for their
      expression. We addressed the hypothesis that immunomodulatory activities of PRL
      might arise from an increase in NF-kappaB activity. MAC-T cells, a bovine mammary
      epithelial cell line, were stimulated with increasing concentrations of bovine
      PRL (1, 5, 25, 125, and 1,000 ng/mL). Level of NF-kappaB binding activity was
      measured and mRNA was evaluated for IL-1beta, IL-6, IL-8, granulocyte-macrophage
      colony-stimulating factor (GMCSF), IFN-gamma, and tumor necrosis factor (TNF)
      alpha, cytokines known to require NF-kappaB for their maximal transcription.
      Prolactin activated NF-kappaB; maximal NF-kappaB activation was weaker with PRL
      than with TNF-alpha at 30 or 180 min poststimulation. In addition, PRL
      significantly amplified, in a dose-dependent manner, mRNA expression of IL-1beta,
      IL-6, IL-8, GMCSF, and TNF-alpha. We measured PRL concentrations in blood and
      milk from healthy and chronic mastitis-infected cows, and studied the
      relationship between the PRL concentration and the degree of inflammation in the
      mammary gland as indirectly assessed by somatic cell counts (SCC). Plasma PRL did
      not differ significantly between healthy and chronic mastitis-affected cows (63.7
      and 67.5 ng/mL, respectively). Milk PRL concentration was significantly increased
      in chronic mastitis-affected quarters with the highest SCC, and had a positive
      significant correlation between SCC, as well as between the number of neutrophils
      present in milk samples. The present findings show that PRL promotes an
      inflammatory response in bovine mammary epithelial cells via NF-kappaB
      activation, and suggest a role for PRL in the pathogenesis of chronic mastitis.

PMID- 17183085
TI  - Effect of continuous milking and bovine somatotropin supplementation on mammary
      epithelial cell turnover.
AB  - Objectives were to determine effects of continuous milking (CM) and bovine
      somatotropin (bST) administration on 1) mammary epithelial cell (MEC)
      proliferation, apoptosis, and ultrastructure during late gestation and early
      lactation, 2) expression of genes associated with proliferation, and apoptosis in
      mammary epithelial cells, and 3) milk yield and composition. Second-gestation,
      first dry-period cows were randomly assigned to either continuous bST throughout
      late gestation and early lactation (+bST; n = 4) or no bST (-bST; n = 4)
      administration. Within each animal, udder halves were randomly assigned to CM or
      a 60-d dry period (control) treatment. Daily milk yield and weekly milk
      composition were measured during the last 60 d of gestation in CM halves and from
      1 to 30 d postpartum for both halves. Mammary biopsies were obtained at -20 +/-
      7, -8 +/- 3, +1 +/- 0, +7 +/- 0, and +20 +/- 0 d (mean +/- standard error)
      relative to parturition. Prepartum half-udder milk yield was greater in +bST cows
      than in -bST cows (9.9 vs. 8.2 kg/d) and postpartum half-udder milk yields were
      dramatically reduced in CM halves compared with control halves (10.6 vs. 22.2
      kg/d), regardless of bST treatment. Proliferation of MEC was reduced in CM halves
      at -8 d (2.7 vs. 5.4%). Apoptosis of MEC was elevated during early lactation for
      d +1 and +7 in control halves, but was only increased at d +1 in CM halves.
      Turnover of MEC was not affected by bST. Ultrastructure data indicated complete
      involution of the control half and lactation maintenance in CM glands (d -20). By
      d -8, control tissue contained alveoli in an immature secretory state, but CM
      tissue contained both lactating and immature alveoli. Postpartum ultrastructure
      parameters were similar between halves until d 20 when control tissue was
      composed of a homogeneous population of lactating alveoli, but CM tissue
      contained lactating, engorged, and resting alveoli. Expression of CCAAT/enhancer
      binding protein-beta (CEBP-beta), cyclin D1, and bcl(2) were up-regulated during
      late gestation, but did not differ between control and CM halves. Expression of
      alpha-lactalbumin was increased in CM halves during late gestation, but was not
      different in CM and control tissue after parturition. Other genes evaluated (bax,
      insulin-like growth factor binding protein 5, ATP-binding cassette 1, and p27)
      were not differentially expressed at any timepoints evaluated. Results indicate
      that CM reduced subsequent half-udder milk yield in primiparous cows through
      altered MEC turnover and secretory capacity. Negative effects of CM on the
      subsequent lactation were not alleviated by bST supplementation.

PMID- 17183086
TI  - The association between reproductive performance and milk yield in Chilean
      Holstein cattle.
AB  - The objective of this study was to evaluate the relationship between reproductive
      performance and milk yield in central-southern Chilean Holstein cattle that
      calved from 1990 to 2003. The analysis included 150,457 lactations obtained from
      a certified recording system. Reproductive indexes included in the study were
      calving interval (CI, d), calving to first service interval (CFSI, d), calving to
      conception interval (CCI, d), services per conception (SC), and conception rate
      at first service (CRFS). Survival analysis for the risk of pregnancy was also
      conducted. Models for reproductive indexes were significant and included, as
      independent variables, year and season of parturition, parity, length of dry
      period, milk and fat production standardized to 305 d, herd size, and herd. In
      1990 and 2003, respectively, means +/- SEM for CI were 399 +/- 1.6 and 415 +/-
      1.1 d; for CFSI were 85 +/- 0.6 and 97 +/- 0.6 d; for CCI were 124 +/- 1.3 d and
      137 +/- 1 d; and for SC were 1.6 +/- 0.02 and 1.7 +/- 0.01. For every 100 kg of
      305-d standardized milk yield, the CCI increased by 0.6 d and CRFS decreased by
      0.9%. Association between milk yield and the risk of pregnancy was almost zero
      when a Cox proportional regression model was conducted (hazard ratio = 1.005; 95%
      confidence interval = 1.002 to 1.008). We conclude that CCI has increased over
      time and is related negatively to the increase in milk yield experienced by
      central-southern Chilean Holstein cattle during the last 15 yr. Nevertheless,
      risk of pregnancy was not explained by the individual level of standardized 305-d
      milk yield of cows studied.

PMID- 17183087
TI  - Curli production and genetic relationships among Escherichia coli from cases of
      bovine mastitis.
AB  - Curli are adhesive surface structures produced by some Escherichia coli and
      Salmonella strains that bind host proteins and activate inflammatory mediators.
      In this study, 61 E. coli isolates from 36 clinical cases of bovine mastitis were
      characterized using enterobacterial repetitive intergenic consensus-PCR and
      screened for their ability to produce curli. Effect of curli production on case
      recovery, based on a return to precase milk yield, was investigated for a subset
      of 43 isolates from 20 quarters of 19 cows. Thirty-five (57%) of 61 isolates were
      curli positive. Fifty-eight of the 61 isolates clustered into 2 clonal groups at
      52% genetic similarity. Genetically diverse E. coli isolates were simultaneously
      cultured from individual cases. Twenty-three isolates from 13 cows were clustered
      in clonal group I, of which 5 cases (38%) were curli positive; 35 isolates from
      22 cows were clustered in clonal group II, of which 15 cases (68%) were curli
      positive. No association was found between genetic similarity and phenotypic
      curli expression of isolates from cows with clinical E. coli mastitis cases.
      Phenotypic curli expression in isolates did not affect recovery of cows' milk
      yield to premastitis production levels.

PMID- 17183088
TI  - Altered vocalization rate during the estrous cycle in dairy cattle.
AB  - Correct detection of estrus is a problem in dairy herds. In practice, several
      procedures exist for detection of estrus besides conventional visual observation
      by humans. These procedures deliver very different results regarding detection of
      estrus. It is known that the calls of female mammals can contain information
      about reproductive status. It is also suspected that the vocalizations of cattle
      contain information about age, sex, dominance status, and stage in the estrous
      cycle. In the present study, a methodology for the continuous automatic recording
      of vocalization of heifers during the periestrous period is presented. It was
      shown in 10 tethered heifers that the estrous climax results in an increase in
      vocalization rate. Vocalization rate of heifers increased approximately 84% from
      d -2 to 0 (related to observed estrus) and approximately 59% from d -1 to d 0.
      After d 0, vocalization rate decreased about 79%. Increased vocalization was
      correlated with the visual observation of estrus by humans. We also found 2
      different structures in the vocalization of heifers. The harmonic structure
      showed regular frequency bands, whereas the nonharmonic structure was noisy. The
      hypothesis that the disharmonic structure increases near the estrous climax was
      confirmed. Hence, it seems possible to get information about stage of the estrous
      cycle of dairy cattle by means of monitoring vocalization. The presented method
      of automatically detecting the rate of cattle vocalization (patent pending) could
      be used solely or in combination with other automated systems for detecting
      estrus and could considerably increase current estrus detection rates once its
      applicability can be demonstrated in nontethered cattle.

PMID- 17183089
TI  - Subclinical and clinical mastitis in heifers following the use of a teat sealant
      precalving.
AB  - This study investigated the effect in heifers of infusion of a bismuth subnitrate
      teat-canal sealant and bacterial intramammary infection (IMI) precalving on
      prevalence of postcalving IMI and incidence of clinical mastitis in the first 2
      wk postcalving. Glands (n = 1,020) from heifers (n = 255) in 5 seasonally
      calving, pasture-fed dairy herds were randomly assigned within heifer to 1 of 4
      treatment groups (no treatment; mammary gland secretion collection; infusion of a
      teat sealant; or sample collection with infusion of teat sealant). Heifers within
      a herd were enrolled on one calendar day, 31 d on average before the planned
      start of the seasonal calving period. Duplicate milk samples were collected from
      each gland within 4 d after calving for bacterial culture. Herd owners collected
      duplicate milk samples, before treatment, for bacterial culture from glands they
      defined as having clinical mastitis. The gland prevalence of IMI precalving was
      15.5% and did not differ between herds. Bacteria isolated precalving included
      coagulase-negative staphylococci (76.9% of all bacteriologically positive
      samples), Streptococcus uberis (14.1%), Staphylococcus aureus (5.1%),
      Corynebacterium spp. (3.8%), and others (0.1%). The presence of an IMI precalving
      increased the risk of an IMI postcalving 3.6-fold and the risk of clinical
      mastitis 4-fold, relative to no IMI precalving. Infusion of the teat sealant
      reduced the risk of postcalving IMI due to Strep. uberis by 84%, and of clinical
      mastitis by 68%. Sampling the glands precalving had no effect on postcalving IMI
      or on clinical mastitis incidence. Use of an internal teat canal sealant in
      heifers precalving may be a useful tool for reducing the risk of subclinical and
      clinical mastitis in heifers.

PMID- 17183090
TI  - Effects of genotype by environment interactions on milk yield, energy balance,
      and protein balance.
AB  - Increases in genetic merit for milk yield are associated with increases in
      mobilization of body reserves. This study assessed the effects of genotype by
      environment (GxE) interactions on milk yield and energy and protein balances.
      Heifers (n = 100) with high or low genetic merit for milk yield were milked 2 or
      3 times a day and received rations of low or high caloric density. The management
      factors were selected to induce substantial differences in milk production levels
      and model different management strategies. The 2 x 2 x 2 factorial arrangement
      enables the assessment of the effects of genotype, environment, and GxE
      interactions. Mean daily energy-corrected milk production in the first 100 d in
      milk varied between 21.8 and 35.2 kg among the groups. The experimental factors
      affected milk production in the presumed direction. Ration was the most
      determinant factor on milk production. Effects of milking frequency and genetic
      merit were significant only in the groups that were fed rations with high caloric
      density. Signs for severe negative energy balances, protein balances, and low
      body condition scores, all of which may be indicative of health risks, were not
      concentrated in the highest producing cows. Feed caloric density and milking
      frequency had stronger effects on energy balances and protein balances, with
      unfavorable effects of low caloric density feed and an extra milking. This
      emphasizes the possible effect of mismanagement on animal health risks. High
      genetic merit cows had significantly lower postpartum body condition scores.
      Genotype x environment interactions existed, but more information is needed to
      determine if cows of different genetic merit for milk yield are differently at
      risk for disease under specific conditions. High milk production levels per se
      will increase allostatic load, but need not compromise the health status of
      relatively young cows. Ongoing one-sided selection for high yield may be combined
      with good animal health, but because high genetic merit for milk yield seems
      intrinsically connected to the allocation of resources from maintenance toward
      milk, this puts increasing demands on farmers' time and management skills.

PMID- 17183091
TI  - Effects of management and genetics on udder health and milk composition in dairy
      cows.
AB  - Milk production per cow has increased significantly as a result of breeding,
      feeding, and other management factors. This study aims to address concerns about
      udder health risks for low- and high-producing dairy cows. In a 2 x 2 x 2
      factorial design, Holstein-Friesian heifers (n = 100) of low or high genetic
      merit for milk production, milked 2 or 3 times a day, and fed a mixed ration with
      low or high energy content, were compared during the first 14 wk of lactation.
      Milk composition and cell counts were determined weekly; quarter milk samples for
      bacteriology were taken in wk 2, 8, and 14; and teat condition was scored in wk
      2, 6, 10, and 14 during the experiment. The experimental factors resulted in
      substantial differences in milk production between treatment groups (24.1 for low
      vs. 25.6 kg/d for high genetic merit; 23.3 for 2 times vs. 26.5 kg/d for 3 times
      daily milking; and 20.9 for low-energy ration vs. 29.0 kg/d for high-energy
      ration). Ration composition was the most important determining factor for milk
      production, but did not affect cell counts or intramammary bacterial infections,
      although cows that received low-energy rations had rougher teat ends than cows
      receiving high-energy rations. This indicates that high production itself is not
      a major risk factor for udder health in the first lactation. A higher milking
      frequency impaired teat condition and improved cell counts in general, but did
      not clearly influence bacteriological status. High genetic merit was related to
      higher cell count, more Staphylococcus, and less Bacillus and other environmental
      pathogens in cultures and did not affect teat condition. The effects of milking
      frequency and feeding on udder health were similar for cows with high and low
      genetic merit. Genetic selection on milk production, without taking udder health
      into account, reduces udder health. As a result, maintaining udder health will
      require increasing the skills and time of dairy farmers who have to divide their
      attention to more cows when farm sizes increase, or selection should put more
      emphasis on udder health traits.

PMID- 17183092
TI  - The profitability of automatic milking on Dutch dairy farms.
AB  - Several studies have reported on the profitability of automatic milking based on
      different simulation models, but a data-based study using actual farm data has
      been lacking. The objective of this study was to analyze the profitability of
      dairy farms having an automatic milking system (AMS) compared with farms using a
      conventional milking system (CMS) based on real accounting data. In total, 62
      farms (31 using an AMS and 31 using a CMS) were analyzed for the year 2003 in a
      case control study. Differences between the years 2002 and 2003 also were
      analyzed by comparing a subgroup of 16 farms with an AMS and 16 farms with a CMS.
      Matching was based on the time of investment in a milking system (same year), the
      total milk production per year, and intensity of land use (kg/ha). Results from
      2003 showed that the farms with an AMS used, on average, 29% less labor than
      farms with a CMS. In contrast, farms using a CMS grew faster (37,132 kg of milk
      quota and 5 dairy cows) than farms with an AMS (-3,756 kg milk quota and 0.5
      dairy cows) between 2002 and 2003. Dairy farmers with a CMS had larger
      (euro7,899) revenues than those with an AMS. However, no difference in the margin
      on dairy production was detected, partly because of numerically greater
      (euro6,822) variable costs on CMS farms. Dairy farms were compared financially
      based on the amount of money that was available for rent, depreciation, interest,
      labor, and profit (RDILP). The CMS farms had more money (euro15,566) available
      for RDILP than the AMS farms. This difference was caused by larger fixed costs
      (excluding labor) for the AMS farms, larger contractor costs (euro6,422), and
      larger costs for gas, water, and electricity (euro1,549). Differences in costs
      for contractors and for gas, water, and electricity were statistically
      significant. When expressed per full-time employee, AMS farms had greater
      revenues, margins, and gross margins per full-time employee than did CMS farms.
      This resulted in a substantially greater (but not statistically significant)
      RDILP per full-time employee (euro12,953) for AMS farms compared with CMS farms.
      Depreciation and interest costs for automatic milking were not available but were
      calculated based on several assumptions. Assuming larger purchase costs and a
      shorter depreciation time for AMS than for CMS, costs for depreciation and
      interest were larger for AMS farms than for CMS farms. Larger fixed costs should
      be compensated for by the amount of labor that has become available after
      introducing the milking robot. Therefore, farm managers should decide whether the
      extra time acquired by automatic milking balances against the extra costs
      associated with an AMS.

PMID- 17183093
TI  - Treatment practices and quantification of antimicrobial drug usage in
      conventional and organic dairy farms in Wisconsin.
AB  - The objective of this study was to develop a method to quantify antimicrobial
      drug usage and treatment practices on conventional and organic dairy farms that
      had been recruited to represent a broad spectrum of potential exposure to
      antimicrobial drugs. Data on disease prevalence and treatment practices of
      organic (n = 20) and conventional (n = 20) farms were obtained during a farm
      visit using a survey instrument. A standardized estimate of antimicrobial drug
      usage was developed using a defined daily dose (DDD) of selected compounds.
      Density of antimicrobial drug usage was expressed as the number of DDD per adult
      cow per year. Differences in prevalence and management of selected diseases
      between conventional and organic farms were identified. The overall estimated
      prevalence of selected diseases was greater for conventional farms compared with
      organic farms. Organic farmers reported use of a variety of nonantimicrobial
      compounds for treatment and prevention of disease. Conventional farmers reported
      that penicillin was the compound most commonly used for dry cow therapy and
      cephapirin was most commonly used for treatment of clinical mastitis. On
      conventional farms, the estimated overall exposure to antimicrobial drugs was
      5.43 DDD per cow per year composed of 3.58 and 1.85 DDD of intramammary and
      parenteral antimicrobial drugs, respectively. Of total intramammary antimicrobial
      drug usage, treatment of clinical mastitis contributed 2.02 DDD compared with
      1.56 DDD attributed to the use of dry cow therapy. Of total parenteral
      treatments, the distribution of exposure was 0.52 (dry cow therapy), 1.43
      (clinical mastitis treatment), 0.39 (treatment of foot disease), 0.14 (treatment
      of respiratory disease), and 0.32 (treatment of metritis) DDD. For treatments of
      foot infections (0.33 DDD), respiratory infections (0.07 DDD), and metritis (0.19
      DDD), the mean density of ceftiofur usage was significantly greater compared with
      other compounds.

PMID- 17183094
TI  - Relationship between antimicrobial drug usage and antimicrobial susceptibility of
      gram-positive mastitis pathogens.
AB  - The objective of this study was to analyze relationships between usage of
      antimicrobial drugs on dairy farms and results of antimicrobial susceptibility
      testing of mastitis pathogens. Exposure to selected antimicrobial drugs (n = 10)
      was standardized by calculation of the number of defined daily doses used per
      cow. Farms (n = 40) were categorized based on amount of antimicrobial exposure:
      organic (no usage); conventional-low usage (conventional farms not using or using
      less than or equal to the first quartile of use of each compound); and
      conventional-high usage (conventional farms using more than the first quartile of
      a particular compound). The minimum inhibitory concentration (MIC) of selected
      antimicrobial drugs was determined using a commercial microbroth dilution system
      for isolates of Staphylococcus aureus (n = 137), coagulase-negative staphylococci
      (CNS, n = 294), and Streptococcus spp. (n = 95) obtained from subclinical
      mastitis infections. Most isolates were inhibited at the lowest dilution tested
      of most antimicrobial drugs. Survival curves for Staph. aureus and CNS
      demonstrated heterogeneity in MIC based on the amount of exposure to penicillin
      and pirlimycin. For CNS, farm type was associated with the MIC of ampicillin and
      tetracycline. For Streptococcus spp., farm type was associated with MIC of
      pirlimycin and tetracycline. For all mastitis pathogens studied, the MIC of
      pirlimycin increased with increasing exposure to defined daily doses of
      pirlimycin. The level of exposure to most other antimicrobial drugs was not
      associated with MIC of mastitis pathogens. A dose-response effect between
      antimicrobial exposure and susceptibility was observed for some pathogen
      antimicrobial combinations, but exposure to other antimicrobial drugs commonly
      used for prevention and treatment of mastitis was not associated with resistance.

PMID- 17183095
TI  - Regulation of interferon-stimulated genes in peripheral blood leukocytes in
      pregnant and bred, nonpregnant dairy cows.
AB  - In ruminants, pregnancy results in up-regulation of a large number of IFN
      stimulated genes (ISG) in the uterus. Recently, one of these genes was also shown
      to increase in peripheral blood leukocytes (PBL) during early pregnancy in sheep.
      Our working hypothesis is that conceptus signaling activates maternal gene
      expression in PBL in dairy cattle. The objectives of this study were to
      characterize ISG expression in PBL from pregnant (n = 20) and bred, nonpregnant
      (n = 30) dairy cows. Steady-state levels of mRNA for Mx1, Mx2, beta2
      microglobulin, ISG-15, IFN regulatory factor-1, and IFN regulatory factor-2 were
      quantified. Holstein cows were synchronized to estrus and artificially
      inseminated (d 0). Blood samples were collected (coccygeal venipuncture) on d 0
      and 16, 18, and 20 d after insemination for progesterone analysis and PBL
      isolation. Pregnancy was confirmed by transrectal ultrasonography at
      approximately 40 d after breeding. A status x day interaction was detected for
      Mx1, Mx2, and ISG-15 gene expression. When analyzed within day, levels of mRNA
      for ISG-15 and Mx1 were greater in pregnant compared with bred, nonpregnant cows
      on d 18 and 20, respectively. Expression of the Mx2 gene increased in the
      pregnant group compared with bred, nonpregnant cows on d 16, 18, and 20 after
      insemination. beta2-Microglobulin, IFN regulatory factor-1, and IFN regulatory
      factor-2 were not different between groups. The results clearly indicated that
      components of the innate immune response are activated in PBL during the period
      of pregnancy recognition and early embryo signaling. The physiological
      implications of these changes on maternal immune function are as yet unknown;
      however, they do provide a unique opportunity to identify bred, nonpregnant, cows
      18 d after insemination in dairy cattle.

PMID- 17183096
TI  - Predictive modeling of Bacillus cereus spores in farm tank milk during grazing
      and housing periods.
AB  - The shelf life of pasteurized dairy products depends partly on the concentration
      of Bacillus cereus spores in raw milk. Based on a translation of contamination
      pathways into chains of unit-operations, 2 simulation models were developed to
      quantitatively identify factors that have the greatest effect on the spore
      concentration in milk. In addition, the models can be used to determine the
      reduction in concentration that could be achieved via measures at the farm level.
      One model predicts the concentration when soil is the source of spores, most
      relevant during grazing of cows. The other model predicts the concentration when
      feed is the main source of spores, most relevant during housing of cows. It was
      estimated that when teats are contaminated with soil, 33% of the farm tank milk
      (FTM) contains more than 3 log(10) spores/L of milk. When feed is the main
      source, this is only 2%. Based on the predicted spore concentrations in FTM, we
      calculated that the average spore concentration in raw milk stored at the dairy
      processor during the grazing period is 3.5 log(10) spores/L of milk and during
      the housing period is 2.1 log(10) spores/L. It was estimated that during the
      grazing period a 99% reduction could be achieved if all farms minimize the soil
      contamination of teats and teat cleaning is optimized. During housing, reduction
      of the concentration by 60% should be feasible by ensuring spore concentrations
      in feed below 3 log(10) spores/g and a pH of the ration offered to the cows below
      5. Implementation of these measures at the farm level ensures that the
      concentration of B. cereus spores in raw milk never exceeds 3 log(10) spores/L.

PMID- 17183097
TI  - Effects of varying doses of supplemental conjugated linoleic acid on production
      and energetic variables during the transition period.
AB  - Supplementing a high dose of dietary conjugated linoleic acid (CLA) inhibits milk
      fat synthesis in dairy cows immediately postpartum. During negative net energy
      balance (EBAL), it appears that moderate CLA-induced milk fat depression causes a
      positive response in milk yield; however, as milk fat depression becomes more
      severe, the milk yield response diminishes. Multiparous Holstein cows (n = 31)
      were randomly assigned to 1 of 3 treatments beginning 9 +/- 6 d before expected
      calving and ceased at 40 d in milk (DIM): 1) 578 g/d of a rumen-inert (RI) palm
      fatty acid distillate (control), 2) 600 g/d of RI-CLA for the entire trial period
      (CLA-1), and 3) 600 g/d of RI-CLA until 10 DIM followed by 200 g/d for the
      remainder of the trial (CLA-2). Each dose provided equal amounts of fatty acids
      by replacing and balancing each treatment with a RI palm fatty acid distillate.
      Doses provided a total of 522 g of fatty acids/ d and 0, 174, or 58 (depending
      upon DIM) g of CLA (mixed isomers)/d. To improve palatability, doses were mixed
      with 600 g/d of dried molasses; one-half of the supplement was fed at 0800 h, and
      the remainder at 1900 h. Individual milk yield, dry matter intake, and body
      weight were recorded daily and milk composition determined every other day. There
      was no overall CLA effect on either the content or yield of milk protein or
      lactose. Both CLA treatments decreased overall milk fat content (26.0 and 18.3%)
      and yield (22.5 and 17.3%) with CLA-induced milk fat depression becoming
      significant by d 8. The CLA-induced milk fat depression increased in magnitude
      with progressing DIM until reaching a plateau on d 18 for CLA-1 (43%) and on d 14
      for CLA-2 (33%), although neither milk fat trans-10, cis-12 CLA content (1.8
      mg/g) nor its transfer efficiency (6.3%) changed over time. Treatments had no
      effect on overall dry matter intake or milk yield, but there was a treatment x
      time interaction for milk production, as cows fed either CLA treatment had
      increased milk yield after the second week of lactation. Cows fed either CLA
      treatment had a significant improvement in overall EBAL (-5.1 vs. -1.8 Mcal/d), a
      decrease in nonesterified fatty acid levels (12%), and an increase in glucose
      levels (11%). A dietary supplement containing trans-10, cis-12 CLA markedly
      improves EBAL and bioenergetic variables and increases milk yield in the total
      mixed ration-fed transitioning dairy cow.

PMID- 17183098
TI  - Herd-level risk factors for lameness in high-producing holstein cows housed in
      freestall barns.
AB  - The objective of this study was to investigate the association of some herd-level
      factors with the prevalence of lameness in 53 high-production groups of Holstein
      cows housed on 50 commercial dairy farms having freestall barns in Minnesota.
      Cows in the high-production group (n = 5,626) were scored for locomotion (score
      of 1 to 5, where 1 = normal and 5 = severely lame) to estimate prevalence of
      lameness (locomotion score >or=3) in the group. Herd-level variables were used to
      explain the variation in prevalence among groups. Among the variables tested,
      herd size, pen space per cow, type and size of milking parlor, total mixed ration
      content of crude protein and neutral detergent fiber, feeding frequency, linear
      feedbunk space per cow, type of feed barrier, and use of footbath did not show
      any association with the prevalence of lameness in the univariate analysis
      screening test and were not included in the multivariate model. Pen stocking
      density (cows per 100 stalls), total daily distance between pen and milking
      parlor, number of cows per full-time employee equivalent, cud chewing index, and
      pen type were eliminated from the multivariate model in the backwards stepwise
      procedure. Daily time away from the pen for milking was positively associated
      with the prevalence of lameness, whereas cow comfort quotient was negatively
      associated with prevalence of lameness. Prevalence of lameness was greater when
      farms performed hoof trimming only when the manager decided cows needed it
      because of hoof overgrowth or lameness compared with farms on which the feet of
      all cows were trimmed on a maintenance schedule once or twice annually. Brisket
      board height of more than 15.24 cm and presence of the area behind the brisket
      board filled with concrete were associated with greater prevalence of lameness.
      Most of these herd-level factors could be managed to reduce lameness prevalence
      in commercial dairy farms.

PMID- 17183099
TI  - Prevalence and risk factors for postpartum anovulatory condition in dairy cows.
AB  - The objectives of this research were to determine the prevalence of the
      anovulatory condition within a temperate region of North America and identify cow
      level and herd-level risk factors for this condition. A total of 1,341 cows from
      18 herds were classified as cycling or anovular based on skim milk progesterone
      concentration determined at 46 and 60 +/- 7 d in milk. Calving history,
      periparturient disease incidence, body condition score, milk ketone concentration
      in the first 2 wk of lactation, and first 305-d mature-equivalent milk
      projections were recorded. Reproductive and culling information was retrieved
      monthly from the Dairy Herd Improvement Association. The cow-level prevalence of
      anovulation was 19.5%, with a herd-specific range from 5 to 45%. Accounting for
      the effect of clustering at the herd level, cows experiencing a difficult
      calving, cows with twin calvings, displaced abomasum, and cows with subclinical
      ketosis in the first week after calving were at greater risk for diagnosis of
      anovulation. Anovular cows within herds using ovulation synchronization programs
      were inseminated at the same time postpartum with a 6-percentage point reduction
      in the probability of pregnancy relative to cycling herdmates (29.7 vs. 35.9%,
      respectively), whereas anovular cows in herds breeding based on observed estrus
      were inseminated 8 d later and suffered a 10-percentage point reduction in the
      probability of pregnancy at first insemination (20.3 vs. 30.5). Time to pregnancy
      was delayed in anovular cows by 30 d (156 vs. 126 d). Using survival analysis,
      the impact of anovulation decreased with time. The daily probability of pregnancy
      (hazard ratio) was similar to cycling cows by 165 d in milk. The results
      underline the important associations of peripartum health with reproductive
      function and performance.

PMID- 17183100
TI  - Plasma concentrations of gut peptides in dairy cattle increase after calving.
AB  - Effects of transition from late gestation to early lactation on plasma
      concentrations of glucose-dependent insulinotropic polypeptide (GIP), glucagon
      like peptide 1-(7-36) amide (GLP-1), and cholecystokinin (CCK) have not been
      reported in cattle. The objective of the present study was to measure plasma
      concentrations of GLP-1, GIP, CCK, insulin, glucose, and nonesterified fatty
      acids in blood plasma obtained from the coccygeal vein of 32 Holstein cows at an
      average of 11 d before, and 5, 12, and 19 d after calving. Feed dry matter intake
      (DMI) averaged 14.4, 17.7, and 19.9 kg/d on d 5, 12, and 19 of lactation,
      respectively, as milk yield increased (30.6, 36.6, and 39.7 kg/d, respectively).
      Plasma concentrations of insulin and glucose were lower postpartum than
      prepartum, but did not differ among samples collected after calving. In contrast,
      plasma concentration of gut peptides increased linearly after calving, perhaps as
      a consequence of increased feed intake and nutrient absorption; however, the
      increases in plasma concentrations of GIP and GLP-1 as lactation progressed were
      not associated with increased DMI per se, and likely reflect the endocrine and
      metabolic adaptations of lacto-genesis. In contrast, increased concentration of
      CCK was related both to increasing days in milk and DMI. By 19 d postpartum,
      concentrations of GLP-1, GIP, and CCK increased by 2.3-, 1.8-, and 2.8-fold,
      respectively, compared with values at 11 d before calving. Although these
      peptides have direct and indirect effects that reduce appetite and DMI in other
      species (including increased insulin secretion), these may be glucose- or insulin
      dependent functions, and insulin and glucose concentrations were reduced in early
      lactation.

PMID- 17183101
TI  - Interventions after artificial insemination: conception rates, pregnancy
      survival, and ovarian responses to gonadotropin-releasing hormone, human
      chorionic gonadotropin, and progesterone.
AB  - We hypothesized that increasing concentrations of progesterone (P4) after
      artificial insemination would increase fertility. Our objective was to assess
      changes in ovarian structures, incidence of ovulation, and change in serum P4 in
      response to GnRH, human chorionic gonadotropin (hCG), or exogenous P4 (controlled
      internal drug release; CIDR insert) treatment beginning 4 to 9 d after artificial
      insemination (d 0) and again 7 d later (experiment 1). Blood was collected from
      753 cows in 3 herds on d 0 and 7. Ovaries of 162 cows were scanned and mapped to
      confirm the presence of a corpus luteum (CL), and cows were assigned randomly to
      serve as controls (n = 41) or to receive a CIDR insert for 7 d (n = 41), 100
      microg of GnRH (n = 40), or 3,300 IU of hCG (n = 40). More cows were induced to
      ovulate in response to GnRH (60%) and hCG (78%) compared with controls (2.4%).
      Compared with controls, cows treated with GnRH or hCG had more induced CL (d 7)
      and more total CL (d 7), but serum P4 was increased only in response to hCG.
      Largest follicle diameters on d 7 were less after GnRH and hCG, but total
      follicular volume on d 7 was reduced by GnRH, hCG, and CIDR, compared with that
      of controls. Volume of the original luteal structures was increased by hCG but
      tended to be reduced by CIDR and GnRH compared with luteal volume in controls.
      Total CL volume was increased by hCG, but reduced by CIDR, compared with CL
      volume of controls. Conception rates and pregnancy survival were assessed in
      response to the same treatments described in experiment 1: controls (n = 708),
      CIDR (n = 711), GnRH (n = 719), and hCG (n = 714). Tendencies for interactions of
      treatment x herd and treatment x lactation group were detected, but no 3-way
      interactions were found. Treatment with hCG increased conception rates in second
      lactation cows. The CIDR tended to increase, and hCG increased, conception rates
      in 2 herds, whereas the CIDR decreased conception rates in 1 herd. Pregnancy
      survival was reduced by GnRH compared with that in controls. We concluded that
      GnRH and hCG effectively induced ovulation, and increased number of CL, but only
      increased serum P4 in hCG-treated cows. Further, treatment with the CIDR or hCG
      increased conception rates but only in some herds.

PMID- 17183102
TI  - Fertility of lactating dairy cows administered recombinant bovine somatotropin
      during heat stress.
AB  - Administration of recombinant bovine somatotropin (bST) to lactating dairy cows
      during heat stress increases milk yield, but it also can increase body
      temperature and may therefore compromise fertility. However, it is possible that
      bST treatment could increase fertility during heat stress because it has been
      reported to increase fertility in lactating cows. In addition, bST increases
      secretion of insulin-like growth factor-I (IGF-I) that promotes embryo survival.
      The purpose of this study was to determine effects of bST on reproductive
      function in lactating dairy cows during heat stress. The experiment was conducted
      in southern Georgia from July to November 2005 using lactating Holstein cows (n =
      276 for reproductive traits). For first service timed artificial insemination
      (TAI), cows were presynchronized with 2 injections of PGF(2alpha) given 14 d
      apart followed by a modified Ovsynch protocol (GnRH and insemination at 72 h
      following PGF(2alpha) ). Pregnancy was diagnosed by using ultrasonography on d 29
      and reconfirmed by palpation between d 45 and 80 post-TAI. Nonpregnant cows were
      resynchronized with the modified Ovsynch protocol and received a second TAI.
      Treatment with bST started 1 wk before the start of Ovsynch and continued at 2-wk
      intervals. Blood samples were collected from a subset of cows to determine IGF-I
      profiles immediately before the first bST injection, 1 wk later, and at d 35 of
      bST treatment. Rectal temperatures were assessed on d 29 of bST treatment.
      Pregnancy rates (d 45 to 80 post-TAI) did not differ between bST and control cows
      for first- (16.7 vs. 15.2%) or second-service TAI (14.8 vs. 17.2%). Plasma
      concentrations of IGF-I and milk yield were greater for bST-treated cows
      following the initiation of bST treatment and bST increased rectal and vaginal
      temperatures. Body condition score was less for bST-treated cows. In conclusion,
      treatment with bST during heat stress increased IGF-I concentrations, milk yield
      over time, and rectal and vaginal temperatures without affecting first- or second
      service pregnancy rates. Thus, at least under certain housing conditions, bST can
      be used to improve milk yield during heat stress without compromising fertility.

PMID- 17183103
TI  - Effect of protein supply on hepatic synthesis of plasma and constitutive proteins
      in lactating dairy cows.
AB  - The effects of metabolizable protein (MP) supply on the synthesis of plasma total
      proteins and albumin, as well as total hepatic protein synthesis, were determined
      in 6 multicatheterized lactating Holstein cows. Three TMR formulated to supply
      the same amount of energy but different amounts of MP, 1,922 (low), 2,264
      (medium), and 2,517 g of MP/d (high), were fed every 2 h according to a double 3
      x 3 Latin square design. For the low and high MP treatments, the cows were
      continuously infused with [(2)H(5)]Phe (d5-Phe) into a jugular vein for 8 h (1.3
      mmol/h) on d 21 of each period. Concentration and isotopic enrichment of d5-Phe
      were measured for free plasma Phe, plasma total proteins, and albumin on hourly
      samples collected between 3 and 8 h. Low MP decreased the plasma albumin
      concentration (32.3 vs. 33.7 +/- 0.11 g/L) but the plasma total protein
      concentration was unchanged (74.1 vs. 75.6 +/- 1.13 g/L). Incorporation of d5-Phe
      over time into both plasma total proteins and albumin was linear (R(2) > 0.98).
      Neither fractional nor absolute synthesis rates of plasma total proteins (6.8 vs.
      6.5 +/- 0.65%/d; 168 vs. 154 +/- 19.9 g/d) or albumin (3.4 vs. 3.4 +/- 0.10%/d;
      36.3 vs. 36.5 +/- 1.11 g/d) were affected by the MP supply. Net hepatic removal
      of Phe was lower with the low-MP diet (-12.3 vs. -20.2 +/- 1.98 mmol/h). As a
      result, net hepatic Phe removal used for total export protein synthesis (17.9 vs.
      11.1 +/- 1.83%) and albumin synthesis (4.6 vs. 2.9 +/- 0.54%) tended to be
      greater at low MP. These results suggest that hepatic synthesis of plasma
      proteins, including albumin, is maintained in lactating dairy cows even when the
      protein supply is reduced.

PMID- 17183104
TI  - Performance of lactating dairy cows fed whole cottonseed coated with gelatinized
      starch plus urea or yeast culture.
AB  - Thirty lactating Holstein cows were used in an 8-wk randomized design trial to
      test the viability of select additives included in the gelatinized corn starch
      coating applied to whole cottonseed (WCS) on nutrient intake and digestibility
      and milk yield and composition. Treatments included WCS coated with 2.5%
      gelatinized corn starch (control); control plus 0.5% urea; or control plus 2.0%
      yeast culture. The treated WCS represented 12.6% of the dietary dry matter.
      Cellulose intake was lower for the control coating compared with either the urea
      or yeast coating because of slightly lower cellulose concentrations in the
      control treatment. Intake of all other nutrients was similar for all treatments.
      Whole-tract nutrient apparent digestibility was not altered by treatment. Dry
      matter intake and milk yield were similar among treatments. Percentage solids-not
      fat was lower for the yeast treatment compared with control, but no other
      differences were observed in milk composition among treatments. Efficiency of
      milk production (energy-corrected milk yield per unit of dry matter intake) was
      higher for the urea and yeast treatments compared with control because of
      slightly higher yield of milk fat and energy-corrected milk. No differences were
      observed in body weight change during the trial between treatments. Results of
      this trial indicate that including urea or yeast culture in the gelatinized
      starch coating does not change whole tract digestibility, but does improve milk
      production efficiency.

PMID- 17183105
TI  - Severity of ruminal acidosis in primiparous holstein cows during the
      periparturient period.
AB  - The objectives of this study were: 1) to determine the effect of providing
      additional prepartum concentrate on the occurrence and severity of ruminal
      acidosis (RA) and lactational performance during the periparturient period in
      primiparous cows; and 2) to characterize the occurrence and severity of RA during
      the periparturient period. We hypothesized that providing additional concentrate
      prepartum would reduce postpartum RA. Fourteen ruminally cannulated Holstein
      heifers were paired by expected calving date and body condition score. The
      heifers were assigned to 1 of 2 prepartum feeding regimens: 1) a control
      treatment consisting of a far-off diet (forage:concentrate, F:C = 80:20) fed from
      d -60 to d -25 and a close-up diet (F:C = 54:46) fed from d -24 until
      parturition; or 2) a high-concentrate (HC) feeding program consisting of 4
      prepartum diets, HC-1 (F:C = 68:32) fed from d -60 to d -43, HC-2 (F:C = 60:40)
      fed from d -42 to d -25, HC-3 (F:C = 52:48) fed from d -24 to d -13, and HC-4
      (F:C = 46:54) fed from d -12 until parturition. All cows received the same
      lactation diet postpartum. Ruminal pH was measured continuously from d -5 to d
      +5, and for 3 consecutive days starting on d +17 +/- 1.2, d +37 +/- 1.4, and d
      +58 +/- 1.5 relative to parturition using an indwelling ruminal pH system.
      Ruminal acidosis was considered to occur when ruminal pH was <5.8 (total RA).
      Ruminal acidosis was further partitioned into: 1) mild RA (5.8 > ruminal pH >
      5.5), 2) moderate RA (5.5 > ruminal pH > 5.2), and 3) acute RA (ruminal pH <
      5.2). Feeding additional concentrate prepartum did not reduce postpartum RA. In
      fact, cows fed the HC treatment had more daily episodes of acute RA than cows fed
      the control treatment. Day relative to parturition affected the occurrence and
      severity of RA; RA increased following parturition and was sustained thereafter.
      The DM intake during the last 5 d of gestation was lower for cows fed the HC
      treatment compared with cows fed the control treatment, but lactational
      performance was not affected. We conclude that, under the conditions imposed,
      feeding additional concentrate prepartum does not reduce postpartum RA.
      Furthermore, the incidence and severity of RA increases immediately postpartum,
      emphasizing the need to develop and implement feeding strategies that reduce this
      risk.

PMID- 17183106
TI  - Associations among body condition score, body weight, and reproductive
      performance in seasonal-calving dairy cattle.
AB  - The objective of the present study was to identify and quantify relationships
      between body condition score (BCS) and body weight (BW) in dairy cows with
      reproduction variables in pasture-based, seasonal-calving dairy herds. Over 2,500
      lactation records from 897 spring-calving Holstein-Friesian dairy cows were used
      in the analyses. Eleven BCS- and 11 BW-related variables were generated,
      including observations at calving, nadir, planned start of mating (PSM), and
      first service, as well as days to nadir and the amount and rate of change between
      periods. The binary reproductive variables were cycling by PSM, mated in the
      first 21 d from PSM, pregnant to first service, and pregnant in the first 21, 42,
      and 84 d of the seasonal mating period. Generalized estimating equations were
      used to identify BCS and BW variables that significantly affected the probability
      of a successful reproductive outcome. After adjusting for the fixed effect of
      year of calving, parity (for cycling by PSM only), and the interval from calving
      to either first service or PSM, reproductive performance was found to be
      significantly affected by BW or BCS at key points, and by BCS and BW change
      during lactation. All reproductive response measures were negatively affected
      when BCS and BW measures indicated an increased severity and duration of the
      postpartum negative energy balance. In particular, cycling by PSM was positively
      associated with calving BCS, whereas pregnancy at 21, 42, and 84 d post-PSM were
      positively associated with nadir BCS and BW gain post-PSM, and negatively
      associated with BCS loss between calving and nadir. The results highlight the
      important role that BCS and BW loss has on reproductive performance, especially
      in seasonal-calving dairy systems because of the short period between calving and
      PSM.

PMID- 17183107
TI  - Composition of milk fat from cows selected for milk fat globule size and offered
      either fresh pasture or a corn silage-based diet.
AB  - The objective of this study was to examine the synthesis and composition of milk
      produced by dairy cows that secrete either small milk fat globules (SMFG) or
      large milk fat globules (LMFG), and to study their response to diets known to
      alter milk composition. Four groups of 3 multiparous dairy cows were assigned to
      2 isoenergetic feeding treatments: a corn silage treatment supplemented with
      soybean meal, and fresh pasture supplemented with cereal concentrate. The 4
      groups comprised 2 groups of 3 dairy cows that produced SMFG (3.44 microm) and 2
      groups of 3 dairy cows that produced LMFG (4.53 microm). The SMFG dairy cows
      produced higher yields of milk, protein, and calcium. Nevertheless, their milk
      had lower fat and protein contents. Both SMFG and LMFG cows secreted similar
      amounts of milk fat; therefore, higher globule membrane contents in milk fat were
      observed in SMFG cows. Higher calcium mineralization of the casein micelles in
      SMFG cows suggests that it may be possible to improve cheese-making properties
      even if the lower protein content may lead to lower cheese yields. The SMFG cows
      secrete milk fat with a higher concentration of monounsaturated fatty acids and a
      lower concentration of short-chain fatty acids. They also have a higher
      C18:1/C18:0 ratio than LMFG cows. This suggests that SMFG cows have more
      significant fatty acid elongation and desaturation. The pasture treatment led to
      an increase in milk and protein yields because of increased energy intake. It
      also resulted in lower milk fat yield and fat and protein contents. The pasture
      treatment led to a decrease in milk fat globule size and, as expected, an
      increase in monounsaturated and polyunsaturated fatty acid contents. However, it
      induced a decrease in the protein content, and in calcium mineralization of
      casein micelles, which suggests that this type of milk would be less suitable for
      making cheese. This study also shows that there is no correlation between the
      cows, based on milk fat globule size and diet. These results open up
      possibilities for improving milk fat quality based on milk fat globule size, and
      composition. The mechanisms involved in milk fat globule secretion are still to
      be determined.

PMID- 17183108
TI  - High growth rate fails to enhance adaptive immune responses of neonatal calves
      and is associated with reduced lymphocyte viability.
AB  - The objective of the study was to evaluate the effects of 3 targeted growth rates
      on adaptive (i.e., antigen-specific) immune responses of preruminant, milk
      replacer-fed calves. Calves (9.1 +/- 2.4 d of age) were assigned randomly to one
      of 3 dietary treatments to achieve 3 targeted daily rates of gain [no growth
      (maintenance) = 0.0 kg/d, low growth = 0.55 kg/d, or high growth = 1.2 kg/d] over
      an 8-wk period. The NRC Nutrient Requirements of Dairy Cattle calf model computer
      program was used to estimate the milk replacer intakes needed to achieve target
      growth rates. All calves were fed a 30% crude protein, 20% fat, all-milk protein
      milk replacer reconstituted to 14% dry matter. Diets were formulated to ensure
      that protein would not be limiting. All calves were vaccinated 3 wk after
      initiation of dietary treatments with Mycobacterium bovis, strain bacillus
      Calmette-Guerin and ovalbumin. Growth rates for no-growth (0.11 kg/d), low-growth
      (0.58 kg/d), and high-growth (1.16 kg/d) calves differed throughout the
      experimental period. Blood glucose concentrations in high-growth calves increased
      with time and were higher than in low- and no-growth calves. Mononuclear and
      polymorphonuclear leukocyte percentages in peripheral blood were unaffected by
      growth rate but did change with advancing age. Percentages of CD4(+) T cells
      increased with age in no-growth and low-growth calves, a characteristic of
      maturation, but failed to increase in high-growth calves. Growth rate did not
      affect the percentages of CD45RO(+) (memory) CD4(+) and CD8(+) T cells, antigen
      (i.e., ovalbumin)-specific serum IgG concentrations, or antigen (i.e., purified
      protein derivative)-induced IFN-gamma and nitric oxide secretion by mononuclear
      cell cultures. Antigen-elicited cutaneous delayed-type hypersensitivity responses
      of no-growth calves exceeded responses of low-growth, but not high-growth,
      calves. In resting- and antigen-stimulated cell cultures, viabilities of CD4(+),
      CD8(+), and gammadeltaTCR(+) T cells from high-growth calves were lower than
      those of the same T cell subsets from no-growth and low-growth calves.
      Alternatively, resting cultures of mononuclear leukocytes from high-growth calves
      produced more nitric oxide than those from no-growth and low-growth calves. In
      conclusion, adaptive immune responses were affected minimally by growth rate. The
      results suggest that protein-energy malnutrition in the absence of weight loss is
      not detrimental to antigen-specific responses of neonatal vaccinated calves and
      that a high growth rate does not enhance these responses. The negative effect of
      a high growth rate on the viability of circulating T cell populations may
      influence infectious disease resistance of the calf.

PMID- 17183109
TI  - Technical note: assessment of recovery site of mobile nylon bags for measuring
      ileal digestibility of starch in dairy cows.
AB  - The objective of this study was to evaluate recovery site of mobile nylon bags
      for measuring ileal digestibility of ruminally undegraded starch in dairy cows.
      Eight feed samples of untreated and treated concentrates were examined. Three
      lactating cows equipped with rumen fistula and duodenal and ileal cannulas were
      used in the experiment. The mobile nylon bags containing intact feeds or residues
      after a 12-h ruminal incubation were pretreated using a 2-step procedure to
      simulate abomasal digestion before insertion through the duodenal cannula. To
      assess the effect of hindgut fermentation on starch digestibility, approximately
      half of the bags were collected from the ileum and half from the feces. The
      results indicate that feed samples should be preincubated in rumen before
      insertion into duodenum, and that samples with relatively high fractions of rumen
      undigestible starch should be collected from the ileum instead of from feces.

PMID- 17183110
TI  - Short communication: detection of quantitative trait loci influencing somatic
      cell score in Spanish Churra sheep.
AB  - Eleven half-sib ovine families, including 1,421 Spanish Churra ewes, were
      analyzed for 181 microsatellite markers spanning the entire autosomic ovine
      genome. Using a multimarker regression method, a daughter experimental design was
      used to identify putative quantitative trait loci (QTL) affecting the somatic
      cell score (SCS). Chromosome-wise significance thresholds were set empirically by
      permuting the phenotypic data. Marker order and genetic distances of the
      autosomic linkage map built for this commercial population were in accordance
      with the published ovine linkage map. An across-family association analysis
      revealed a region on chromosome 20 suggestive of evidence for a QTL. Segregation
      of the QTL into 2 families was inferred from the within-family analysis, and
      differences in the position of the suggested QTL were found between the 2 half
      sib groups. This could be the result of incomplete information associated with
      the markers for the significant families. The location of the major
      histocompatibility complex in proximity to the across-family effect suggests this
      region may harbor a segregating QTL for the SCS in the Churra population. Studies
      in dairy cattle examining the SCS have reported linkage associations on
      corresponding bovine orthologous regions, supporting the validity of our
      findings.

PMID- 17183111
TI  - Genetic analysis of postpartum measures of luteal activity in dairy cows.
AB  - The objective of this study was to estimate genetic parameters for measures of
      luteal activity during the first 60 d postpartum. Analyses were made with
      different sampling intervals to investigate the possibility of combining
      progesterone measurement with routinely performed milk recording. Progesterone
      level in milk as an indicator of female fertility when selecting sires in a
      progeny-testing scheme was also examined. Data were collected from 1996 to 1999,
      and comprised 1,212 lactations from 1,080 British Holstein-Friesian cows at 8
      commercial dairy farms in the United Kingdom. Milk samples for progesterone
      analysis were collected thrice weekly. Mixed linear animal models were used to
      analyze the data. Heritability for the percentage of samples with luteal activity
      during the first 60 d postpartum (PLA) was 0.30 and decreased with more
      infrequent sampling to 0.25, 0.20, and 0.14 for weekly, twice-monthly, and
      monthly sampling, respectively. Measures of PLA had a high negative genetic
      correlation with prolonged anovulation (-0.53 for monthly sampling, < -0.87
      otherwise) and a moderate positive genetic correlation with persistent corpus
      luteum in the first estrus cycle (>0.65 if at least twice-monthly sampling).
      Genetic correlations with interval from calving to commencement of luteal
      activity were close to -1 for all PLA measurements and the selection index
      calculations showed that monthly progesterone sampling could be used with high
      accuracy (0.80 with 50 daughters per bull) to predict breeding values for
      commencement of luteal activity. Progesterone analysis at the time of regular
      milk recording could thereby be used to select for an early interval from calving
      to commencement of luteal activity and, at the same time, a decreased frequency
      of prolonged anovulation during the postpartum period.

PMID- 17183112
TI  - Genetic analysis of somatic cell scores in US Holsteins with a Bayesian mixture
      model.
AB  - The objective of this study was to apply finite mixture models to field data for
      somatic cell scores (SCS) for estimation of genetic parameters. Data were
      approximately 170,000 test-day records for SCS from first-parity Holstein cows in
      Wisconsin. Five different models of increasing level of complexity were fitted.
      Model 1 was the standard single-component model, and the others were 2-component
      Gaussian mixtures consisting of similar but distinct linear models. All mixture
      models (i.e., 2 to 5) included separate means for the 2 components. Model 2
      assumed entirely homogeneous variances for both components. Models 3 and 4
      assumed heterogeneous variances for either residual (model 3) or genetic and
      permanent environmental variances (model 4). Model 5 was the most complex, in
      which variances of all random effects were allowed to vary across components. A
      Bayesian approach was applied and Gibbs sampling was used to obtain posterior
      estimates. Five chains of 205,000 cycles were generated for each model. Estimates
      of variance components were based on posterior means. Models were compared by use
      of the deviance information criterion. Based on the deviance information
      criterion, all mixture models were superior to the linear model for analysis of
      SCS. The best model was one in which genetic and PE variances were heterogeneous,
      but residual variances were homogeneous. The genetic analysis suggested that SCS
      in healthy and infected cattle are different traits, because the genetic
      correlation between SCS in the 2 components of 0.13 was significantly different
      from unity.

PMID- 17183113
TI  - Genetic parameters of growth in dairy cattle and associations between growth and
      health traits.
AB  - Body weight (BW) observations on dairy cattle taken on average 35 times between
      birth and 1,000 d of life were used to estimate daily heritabilities and predict
      daily breeding values for both pregnancy-adjusted BW (PABW) and growth rate.
      Daily heritabilities for PABW were moderate to high, ranging from 0.41 (+/-0.027)
      to 0.82 (+/-0.041). Daily heritabilities for growth rate were high (>0.68 +/-
      0.034). The genetic association between various health events, including mastitis
      and lameness, and weight and growth was investigated by regressing the incidence
      of health events on breeding values for weight at birth, weaning, calving, and
      growth rate at 56 d after calving, growth rate at 110 d after calving, and
      maximum growth rate. Growth at weaning was the only BW measure to significantly
      affect mastitis (r(g) = 0.24), indicating that cows growing faster at weaning are
      more prone to mastitis. Increased weight (r(g) = 0.65) and growth rate at weaning
      (r(g) = 0.38) and increased maximum growth rate (r(g) = 0.71) all contributed to
      increased feet disorders. The only significant negative genetic association was
      obtained between reproduction and weight at calving (r(g) = -0.61).

PMID- 17183114
TI  - Development of a single nucleotide polymorphism genotyping microarray platform
      for the identification of bovine milk protein genetic polymorphisms.
AB  - The objective of this study was to develop and validate a fast method for typing
      the main mutations of bovine milk protein genes by using microarray technology.
      An approach based on the ligation detection reaction (LDR) and a universal array
      (UA) was used. Polymorphisms in both the coding and noncoding sequences of
      alpha(S1)-casein, beta-casein, kappa-casein, and beta-lactoglobulin genes were
      considered because of their well-known effects on milk composition and cheese
      production. A total of 22 polymorphic sites, corresponding to 21 different
      variants, were included in the diagnostic microarray. First, a multiplex PCR was
      developed to amplify all the DNA target sequences simultaneously. Second, the LDR
      UA assay was implemented. The method was validated by analyzing 100 Italian
      Friesian DNA samples, which were also genotyped by conventional methods both at
      the protein level by means of milk isoelectrofocusing and at the molecular level
      using PCR-RFLP and PCR-single strand conformation polymorphism techniques. The
      genotypes obtained using the LDR-UA approach were in full agreement with those
      obtained by the conventional analyses. An important result of the LDR-UA assay
      was a more accurate genotyping of the different milk protein alleles than was
      found with conventional typing methods. At the kappa-casein gene, in fact, 4
      samples were heterozygous (3 reference samples and 1 validation sample) for an
      allele coding for Thr(136) and Ala(148). This variant, which can be considered as
      the wild type of the genus Bos, is not usually identifiable by the conventional
      typing methods used. The multiplex PCR-LDR-UA approach developed provides for an
      accurate, inexpensive, and high-throughput assay that does not exhibit false
      positive or false negative signals, thus making it highly suitable for animal
      genotyping.

PMID- 17183115
TI  - Linear and curvilinear effects of inbreeding on production traits for walloon
      Holstein cows.
AB  - The nonlinear effects of inbreeding were studied by comparing linear and
      curvilinear regression models of phenotypic performances on inbreeding
      coefficients for production traits (milk, fat, and protein yields) of Holstein
      cows in their first lactation. Three different regression models (linear,
      quadratic, and cubic) were introduced separately into a single-trait, single
      lactation, random regression test-day model. The significance of the different
      regression coefficients was studied based on a t-test after estimation of error
      variances and covariances associated with the different regression coefficients.
      All of the tested regression coefficients were significantly different from 0.
      The traditional regression coefficients of milk, fat, and protein yields on
      inbreeding were, respectively, -22.10, -1.10, and -0.72 kg for Holstein cows in
      their first lactation. However, the estimates of 305-d production losses for
      various classes of animals based on inbreeding coefficients showed that the
      effect of inbreeding was not a linear function of the percentage of inbreeding.
      The 305-d milk yield loss profiles attributable to inbreeding, obtained by the
      various regression models, were different. However, for inbreeding coefficients
      between 0 and 10%, these differences were small.

PMID- 17183116
TI  - Detection of quantitative trait loci affecting lameness and leg conformation
      traits in Danish Holstein cattle.
AB  - Lameness is an important factor for culling animals. Strong legs and feet improve
      herd life of dairy cows. Therefore, many countries include leg and feet
      conformation traits in their breeding programs, often as early predictors of
      longevity. However, few countries directly measure lameness related traits to
      include these in a breeding program. Lameness indices in 3 different lactations
      and 5 leg conformation traits (rear legs side view, rear legs rear view, hock
      quality, bone quality, and foot angle) were measured on granddaughters of 19
      Danish Holstein grandsires with 33 to 105 sons. A genome scan was performed to
      detect quantitative trait loci (QTL) based on the 29 autosomes using
      microsatellite markers. Data were analyzed across and within families for QTL
      affecting lameness and leg conformation traits. A regression method and a
      variance component method were used for QTL detection. Two QTL each for lameness
      in the first [Bos taurus autosome (BTA); BTA5, BTA26] and second (BTA19, BTA22)
      lactations were detected. For the 5 different leg conformation traits, 7
      chromosome-wise significant QTL were detected across families for rear legs side
      view, 5 for rear legs rear view, 4 for hock quality, 4 for bone quality, and 1
      for foot angle. For those chromosomes where a QTL associated with 2 different
      traits was detected (BTA1, BTA11, BTA15, BTA26, and BTA27), a multitrait-1-QTL
      model and a multitrait-2-QTL model were performed to characterize these QTL as
      single QTL with pleiotropic effects or distinct QTL.

PMID- 17183117
TI  - Within-herd heritability estimated with daughter-parent regression for yield and
      somatic cell score.
AB  - Estimates of heritability within herd (h(WH)(2) ) that were generated with
      daughter-dam regression, daughter-sire regression, and REML were compared, and
      effects of adjusting lactation records for within-herd heritability on genetic
      evaluations were evaluated. Holstein records for milk, fat, and protein yields
      and somatic cell score (SCS) from the USDA national database represented herds in
      the US Northeast, Southeast, Midwest, and West. Four data subsets (457 to 499
      herds) were randomly selected, and a large-herd subset included the 15 largest
      herds from the West and 10 largest herds from other regions. Subset
      heritabilities for yield and SCS were estimated assuming a regression model that
      included fixed covariates for effects of dam yield or SCS, sire predicted
      transmitting ability (PTA) for yield or SCS, herd-year-season of calving, and age
      within parity. Dam records and sire PTA were nested within herd as random
      covariates to generate within-herd heritability estimates that were regressed
      toward mean h(WH)(2) for the random subset. Heritabilities were estimated with
      REML using sire models (REML(SIRE)), sire-maternal grandsire models (REML(MGS)),
      and animal models (REML(ANIM)) for each herd individually in the large-herd
      subset. Phenotypic variance for each herd was estimated from herd residual
      variance after adjusting for effects of year-season and age within parity.
      Deviations from herd-year-season mean were standardized to constant genetic
      variance across herds, and records were weighted according to estimated error
      variance to accommodate h(WH)(2) when estimating breeding values. Mean h(WH)(2)
      tended to be higher with daughter-dam regression (0.35 for milk yield) than with
      daughter-sire regression (0.24 for milk yield). Heritability estimates varied
      widely across herds (0.04 to 0.67 for milk yield estimated with daughter-dam
      regression), and h(WH)(2) deviated from subset means more for large herds than
      for small herds. Correlation with REML(ANIM) h(WH)(2) was 0.68 for daughter-dam
      and was 0.45 for daughter-sire h(WH)(2) for milk yield. The correlation between
      daughter-sire h(WH)(2) and REML(MGS) was greater than the correlation between
      daughter-dam h(WH)(2) and REML(MGS). Data adjustments had a minimal impact on
      breeding value bias. Within-herd heritability can be estimated rapidly using
      regression techniques with moderate accuracy, but adjusting lactation records for
      h(WH)(2) resulted in only a small improvement in the accuracy of genetic
      evaluations.

PMID- 17183118
TI  - Nonparametric analysis of the impact of inbreeding on production in Jersey cows.
AB  - Under dominance, the relationship between a quantitative trait and the inbreeding
      coefficient (F) is expected to be linear. Epistasis involving dominance effects
      or selection against inbred individuals can produce nonlinear patterns in the
      form of inbreeding depression. The form of the relationship between F and yield
      traits was explored via local regression (LOESS). First-lactation milk, fat, and
      protein records from 59,778 Jersey cows with at least 6 generations of known
      pedigree were used. The F ranged from 0.6 to 34% and median F was 6.3%. The LOESS
      regressions of predicted residuals from an animal model (empirical best linear
      unbiased predictions, EBLUP) on F were calculated for each trait; the EBLUP model
      included fixed herd-year-season, age at calving and DIM effects, and random
      additive genetic effects. The relationship between EBLUP residuals and inbreeding
      was complex and nonlinear. Yields were unaffected for F <or=7%, and inbreeding
      depression seemed to stabilize at F >20% for fat and protein yield. For SCS, both
      parametric and LOESS fits were consistent with the absence of sizable dominance
      effects. Effects of inbreeding on performance seemed to be more complex than
      suggested by previous studies based on linear regression. Results should be
      interpreted with caution because the data were scarce at high levels of F.

PMID- 17183119
TI  - Genetic parameters for yield traits of cows treated or not treated with bovine
      somatotropin.
AB  - The objective of this study was to estimate genetic correlations between yield
      traits of cows treated with bovine somatotropin (bST) and the same yield traits
      of untreated cows. Lactation records from registered Holstein cows were divided
      by parity into 3 data sets: 1, 2, and 3 through 5. Approximately 10% of the
      records in each data set were from cows treated with bST. The numbers of records
      of treated and untreated cows in the data sets were 4,337 and 48,765; 3,730 and
      37,796; and 3,645 and 33,957. Two-trait animal models (records for cows treated
      or not treated) were used to estimate genetic parameters for milk production
      traits and somatic cell score (SCS). Estimates of heritability for milk yield for
      records of treated and untreated cows for the 3 data sets were 0.13, 0.16, and
      0.09, and 0.18, 0.18, and 0.14, respectively, with estimates of repeatability of
      0.50 and 0.41 for data set 3. Estimates of heritability for fat yield for records
      of treated and untreated cows were 0.31, 0.16, and 0.12, and 0.27, 0.21, and
      0.16. Estimates of repeatability were 0.50 and 0.43 for data set 3. Heritability
      estimates for protein yield for records of treated and untreated cows were 0.13,
      0.17, and 0.12, and 0.20, 0.23, and 0.16, with estimates of repeatability of 0.52
      and 0.47. Estimates of heritability for SCS for treated and untreated cows were
      0.08, 0.15, and 0.13, and 0.11, 0.13, and 0.13 with repeatability estimates of
      0.52 and 0.45. Estimates of genetic correlations between milk yields with and
      without bST treatment in lactations 1, 2, and 3 to 5 were all 0.99. Estimates of
      genetic correlations for fat and protein yields were 0.96 for all data sets.
      Estimates for SCS were 0.99. Estimates of genetic correlations between records of
      treated and untreated cows were large enough to conclude that records of treated
      and untreated cows could be considered to be one trait, with treatment as a fixed
      effect to account for differences in means.

PMID- 17183120
TI  - Evaluation of protein fractionation systems used in formulating rations for dairy
      cattle.
AB  - Production efficiency decreases when diets are not properly balanced for protein.
      Sensitivity analyses of the protein fractionation schemes used by the National
      Research Council Nutrient Requirement of Dairy Cattle (NRC) and the Cornell Net
      Carbohydrate and Protein System (CNCPS) were conducted to assess the influence of
      the uncertainty in feed inputs and the assumptions underlying the CNCPS scheme on
      metabolizable protein and amino acid predictions. Monte Carlo techniques were
      used. Two lactating dairy cow diets with low and high protein content were
      developed for the analysis. A feed database provided by a commercial laboratory
      and published sources were used to obtain the distributions and correlations of
      the input variables. Spreadsheet versions of the models were used. Both models
      behaved similarly when variation in protein fractionation was taken into account.
      The maximal impact of variation on metabolizable protein from rumen-undegradable
      protein (RUP) was 2.5 (CNCPS) and 3.0 (NRC) kg/d of allowable milk for the low
      protein diet, and 3.5 (CNCPS) and 3.9 (NRC) kg/d of allowable milk for the high
      protein diet. The RUP flows were sensitive to ruminal degradation rates of the B
      protein fraction in NRC and of the B2 protein fraction in the CNCPS for protein
      supplements, energy concentrates, and forages. Absorbed Met and Lys flows were
      also sensitive to intestinal digestibility of RUP, and the CNCPS model was
      sensitive to acid detergent insoluble crude protein and its assumption of
      complete unavailability. Neither the intestinal digestibility of the RUP nor the
      protein degradation rates are routinely measured. Approaches need to be developed
      to account for their variability. Research is needed to provide better methods
      for measuring pool sizes and ruminal digestion rates for protein fractionation
      systems.

PMID- 17183121
TI  - Electron radiotherapy: a study on dosimetric uncertainty using small cutouts.
AB  - This note investigated the dosimetric uncertainties due to the positional error
      when centring a small cutout to the machine central beam axis (CAX) in electron
      radiotherapy. A group of six circular cutouts with 4 cm diameter were made with
      their centres shifting 0, 2, 4, 6, 8 and 10 mm from the machine CAX for the 6 x 6
      cm(2) applicator. The per cent depth doses, beam profiles and output factors were
      measured using the 4, 9 and 16 MeV clinical electron beams produced by a Varian
      21 EX linear accelerator. The 2D isodose distributions in the z-x (or cross-line)
      and z-y (or in-line) plane were calculated by Monte Carlo simulation using the
      EGSnrc system. When the cutout centre was shifted away from the machine CAX for
      the 4 MeV beam, the d(m), R(80) and R(90) at the machine CAX had no significant
      change (<0.1 mm). For higher energies of 9 and 16 MeV beams, the d(m) was reduced
      by 0.45 and 1.63 mm per mm, between the cutout centre and the machine CAX with
      off-axis shift <6 mm respectively. R(80) and R(90) were reduced by more than 0.3
      mm per mm off-axis shift for both energies. The isodose coverage of the in-line
      axis beam profile was reduced when the cutout centre was shifted away from
      machine CAX. It is important for oncology staff to note such dosimetric changes
      in the clinical electron radiotherapy, particularly when a high energy electron
      beam is used for small cutout. Such positional uncertainty is unavoidable in
      fabricating an electron cutout in the mould room.

PMID- 17183122
TI  - Evaluation of mineral oil as an acoustic coupling medium in clinical MRgFUS.
AB  - We empirically evaluate mineral oil as an alternative to the mixture of de-gassed
      water and ultrasound gel, which is currently used as an acoustic coupling medium
      in clinical magnetic resonance guided focused ultrasound (MRgFUS) treatments. The
      tests were performed on an ExAblate 2000 MRgFUS system (InSightec Inc., Haifa,
      Israel) using a clinical patient set-up. Acoustic reflections, treatment
      temperatures, sonication spot dimensions and position with respect to target
      location were measured, using both coupling media, in repeated sonications in a
      tissue mimicking gel phantom. In comparison with the water-gel mix, strengths of
      acoustic reflections from coupling layers prepared with mineral oil were on
      average 39% lower and the difference was found to be statistically significant (p
      = 3.3 x 10(-8)). The treatment temperatures were found to be statistically
      equivalent for both coupling media, although temperatures corresponding to
      mineral oil tended to be somewhat higher (on average 1.9 degrees C) and their
      standard deviations were reduced by about 1 degrees C. Measurements of sonication
      spot dimensions and positions with respect to target location did not reveal
      systematic differences. We conclude that mineral oil may be used as an effective
      non-evaporating acoustic coupling medium for clinical MRgFUS treatments.

PMID- 17183123
TI  - Evaluation of MLC leaf positioning using a scanning liquid ionization chamber
      EPID.
AB  - A method was developed to determine the accuracy of multileaf collimator (MLC)
      positioning using transmitted dose maps measured by a scanning liquid ionization
      chamber electronic portal imaging device (SLIC-EPID). Several MLC fields were
      designed, using the Varian C-series standard MLC-80, as reference fields for open
      fields. The MLC leaves were then shifted from the reference positions along the
      direction of MLC leaf movement towards the central axis from 0.1 to 1.6 mm. The
      electronic portal images (EPIs), acquired for each case, were converted to two
      dimensional dose maps using an appropriate calibration method and the relative
      dose difference maps were then calculated. The experiment was then performed at
      non-zero gantry angles in the presence of an anthropomorphic phantom for typical
      prostate and head and neck fields. Several standard edge detection algorithms
      were also used in order to find the shifted MLC leaf position. In addition, the
      short-term reproducibility of MLC leaf positioning was evaluated using the above
      mentioned methods. It was found that the relationship between the relative dose
      difference and MLC leaf spatial displacement is linear. A variation of 0.2 mm in
      leaf position leads to approximately 4% change in the relative dose values for
      open fields. The variation of the relative dose difference for phantom studies
      depends on the phantom positioning and the EPI normalization. From the standard
      edge detection algorithms, used in the current study, the 'Canny' algorithm was
      found to be the optimum method to identify the minimum detectable MLC leaf
      displacements with a precision of approximately 0.1 mm for all cases. However,
      the result of edge detection algorithms generally is binary and there is no
      additional information compared to the relative dose maps. The reproducibility of
      MLC positions was found to be within 0.3 mm. In conclusion, a SLIC-EPID can be
      used for regular quality assurance (QA) of MLC leaf positioning. Despite
      significant difference in the pixel size of the acquired SLIC-EPIs, it can be
      concluded that the SLIC-EPID can be used for MLC quality assurance protocols with
      similar accuracy compared to amorphous silicon (a-Si) EPID results.

PMID- 17183124
TI  - Strategy of extraction methods and reconstruction algorithms in computed
      tomography of diffraction enhanced imaging.
AB  - Computed tomography of diffraction enhanced imaging (DEI-CT) is a novel x-ray
      phase-contrast computed tomography which is applied to inspect weakly absorbing
      low-Z samples. Refraction-angle images which are extracted from a series of raw
      DEI images measured in different positions of the rocking curve of the analyser
      can be regarded as projections of DEI-CT. Based on them, the distribution of
      refractive index decrement in the sample can be reconstructed according to the
      principles of CT. How to combine extraction methods and reconstruction algorithms
      to obtain the most accurate reconstructed results is investigated in detail in
      this paper. Two kinds of comparison, the comparison of different extraction
      methods and the comparison between "two-step" algorithms and the Hilbert filtered
      backprojection (HFBP) algorithm, draw the conclusion that the HFBP algorithm
      based on the maximum refraction-angle (MRA) method may be the best combination at
      present. Though all current extraction methods including the MRA method are
      approximate methods and cannot calculate very large refraction-angle values, the
      HFBP algorithm based on the MRA method is able to provide quite acceptable
      estimations of the distribution of refractive index decrement of the sample. The
      conclusion is proved by the experimental results at the Beijing Synchrotron
      Radiation Facility.

PMID- 17183125
TI  - Signal-to-noise ratio, contrast-to-noise ratio and their trade-offs with
      resolution in axial-shear strain elastography.
AB  - In axial-shear strain elastography, the local axial-shear strain resulting from
      the application of quasi-static axial compression to an inhomogeneous material is
      imaged. In this paper, we investigated the image quality of the axial-shear
      strain estimates in terms of the signal-to-noise ratio (SNR(asse)) and contrast
      to-noise ratio (CNR(asse)) using simulations and experiments. Specifically, we
      investigated the influence of the system parameters (beamwidth, transducer
      element pitch and bandwidth), signal processing parameters (correlation window
      length and axial window shift) and mechanical parameters (Young's modulus
      contrast, applied axial strain) on the SNR(asse) and CNR(asse). The results of
      the study show that the CNR(asse) (SNR(asse)) is maximum for axial-shear strain
      values in the range of 0.005-0.03. For the inclusion/background modulus contrast
      range considered in this study (<10), the CNR(asse) (SNR(asse)) is maximum for
      applied axial compressive strain values in the range of 0.005%-0.03%. This
      suggests that the RF data acquired during axial elastography can be used to
      obtain axial-shear strain elastograms, since this range is typically used in
      axial elastography as well. The CNR(asse) (SNR(asse)) remains almost constant
      with an increase in the beamwidth while it increases as the pitch increases. As
      expected, the axial shift had only a weak influence on the CNR(asse) (SNR(asse))
      of the axial-shear strain estimates. We observed that the differential estimates
      of the axial-shear strain involve a trade-off between the CNR(asse) (SNR(asse))
      and the spatial resolution only with respect to pitch and not with respect to
      signal processing parameters. Simulation studies were performed to confirm such
      an observation. The results demonstrate a trade-off between CNR(asse) and the
      resolution with respect to pitch.

PMID- 17183126
TI  - Evaluation of ultrasonic scattering in human cancellous bone by using a binary
      mixture model.
AB  - A weak scattering model based on small perturbations in a binary mixture is
      developed to estimate the ultrasonic scattering from human cancellous bone, which
      is modelled as a random isotropic continuum containing identical scatters.
      Ultrasonic scattering is determined by both velocity fluctuation and density
      fluctuation, when k(2)a(2) << 1 is satisfied. Two kinds of trabeculae thickness
      distributions, i.e. even distribution and Gauss distribution, are applied in the
      calculation of attenuation and backscattering. Frequency dependence of the
      backscatter coefficient is found to be Af(3.13) and Af(2.84) with the Gauss
      distribution and an even distribution, respectively. Both backscattering and
      attenuation change significantly against porosity for the case of high porosity.
      The predicted results are close to the measured ones from the literature. The
      errors of this theoretical model are also discussed in this paper.

PMID- 17183127
TI  - Consideration of the ICRP 2006 revised tissue weighting factors on age-dependent
      values of the effective dose for external photons.
AB  - The effective dose recommended by the International Commission on Radiological
      Protection (ICRP) is the sum of organ equivalent doses weighted by corresponding
      tissue weighting factors, w(T). ICRP is in the process of revising its 1990
      recommendations on the effective dose where new values of organs and tissue
      weighting factors have been proposed and published in draft form for consultation
      by the radiological protection community. In its 5 June 2006 draft
      recommendations, new organs and tissues have been introduced in the effective
      dose which do not exist within the 1987 Oak Ridge National Laboratory (ORNL)
      phantom series (e.g., salivary glands). Recently, the investigators at University
      of Florida have updated the series of ORNL phantoms by implementing new organ
      models and adopting organ-specific elemental composition and densities. In this
      study, the effective dose changes caused by the transition from the current
      recommendation of ICRP Publication 60 to the 2006 draft recommendations were
      investigated for external photon irradiation across the range of ICRP reference
      ages (newborn, 1-year, 5-year, 10-year, 15-year and adult) and for six idealized
      irradiation geometries: anterior-posterior (AP), posterior-anterior (PA), left
      lateral (LLAT), right-lateral (RLAT), rotational (ROT) and isotropic (ISO). Organ
      absorbed doses were calculated by implementing the revised ORNL phantoms in the
      Monte Carlo radiation transport code, MCNPX2.5, after which effective doses were
      calculated under the 1990 and draft 2006 evaluation schemes of the ICRP.
      Effective doses calculated under the 2006 draft scheme were slightly higher than
      estimated under ICRP Publication 60 methods for all irradiation geometries
      exclusive of the AP geometry where an opposite trend was observed. The effective
      doses of the adult phantom were more greatly affected by the change in tissue
      weighting factors than that seen within the paediatric members of the phantom
      series. Additionally, dose conversion coefficients for newly identified
      radiosensitive organs--salivary glands, gall bladder, heart and prostate--were
      reported, as well as the brain, which was originally considered in ICRP
      Publication 60 as a member of the remainder category of the effective dose.

PMID- 17183128
TI  - Empirical angle-dependent Biot and MBA models for acoustic anisotropy in
      cancellous bone.
AB  - The Biot and the modified Biot-Attenborough (MBA) models have been found useful
      to understand ultrasonic wave propagation in cancellous bone. However, neither of
      the models, as previously applied to cancellous bone, allows for the angular
      dependence of acoustic properties with direction. The present study aims to
      account for the acoustic anisotropy in cancellous bone, by introducing empirical
      angle-dependent input parameters, as defined for a highly oriented structure,
      into the Biot and the MBA models. The anisotropy of the angle-dependent Biot
      model is attributed to the variation in the elastic moduli of the skeletal frame
      with respect to the trabecular alignment. The angle-dependent MBA model employs a
      simple empirical way of using the parametric fit for the fast and the slow wave
      speeds. The angle-dependent models were used to predict both the fast and slow
      wave velocities as a function of propagation angle with respect to the trabecular
      alignment of cancellous bone. The predictions were compared with those of the
      Schoenberg model for anisotropy in cancellous bone and in vitro experimental
      measurements from the literature. The angle-dependent models successfully
      predicted the angular dependence of phase velocity of the fast wave with
      direction. The root-mean-square errors of the measured versus predicted fast wave
      velocities were 79.2 m s(-1) (angle-dependent Biot model) and 36.1 m s(-1) (angle
      dependent MBA model). They also predicted the fact that the slow wave is nearly
      independent of propagation angle for angles about 50 degrees , but consistently
      underestimated the slow wave velocity with the root-mean-square errors of 187.2 m
      s(-1) (angle-dependent Biot model) and 240.8 m s(-1) (angle-dependent MBA model).
      The study indicates that the angle-dependent models reasonably replicate the
      acoustic anisotropy in cancellous bone.

PMID- 17183129
TI  - Reproducibility of reference tissue quantification of dynamic contrast-enhanced
      data: comparison with a fixed vascular input function.
AB  - Reference tissues are currently used to analyse dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) data. The assessment of tumour response to
      treatment with anti-cancer drugs is a particularly important application of this
      type of analysis and requires a measure of reproducibility to define a level
      above which a significant change due to therapy can be inferred. This study
      compares the reproducibility of such quantification strategies with that found
      using a published, group-averaged uptake curve. It is shown that reference tissue
      quantification gives poorer reproducibility for most parameters than that found
      using a group-averaged plasma curve (a change in K(trans) of greater than 41.8%
      and 16.4% would be considered significant in the two approaches, respectively),
      but successfully incorporates some of the variability observed in plasma kinetics
      between visits and provides vascular input functions that, across the group, are
      comparable with the group-averaged curve. This study therefore provides an
      indirect validation of the methodology.

PMID- 17183130
TI  - 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in
      vivo porcine model of lung tumours.
AB  - The purpose of this study was to validate the accuracy and reliability of volume
      measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US)
      imaging. Artificial "tumours" were created by injecting a liquid agar mixture
      into spherical moulds of known volume. Once solidified, the "tumours" were
      implanted into the lung tissue in both a porcine lung sample ex vivo and a
      surgical porcine model in vivo. 3D US images were created by mechanically
      rotating the thoracoscopic ultrasound probe about its long axis while the
      transducer was maintained in close contact with the tissue. Volume measurements
      were made by one observer using the ultrasound images and a manual-radial
      segmentation technique and these were compared with the known volumes of the
      agar. In vitro measurements had average accuracy and precision of 4.76% and
      1.77%, respectively; in vivo measurements had average accuracy and precision of
      8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to
      accurately and reproducibly measure "tumour" volumes both in vivo and ex vivo.

PMID- 17183131
TI  - Circular CT in combination with a helical segment.
AB  - The combination of circular CT with a helical trajectory segment results in a
      mathematically complete data set. We present a reconstruction algorithm which is
      mathematically exact and of the filtered back-projection type. The algorithm
      ensures that only Radon planes which are not covered along the circle are taken
      into account, when data from the helical segment are back-projected. Therefore,
      the helical segment contributes only to low-frequency parts of trans-axial
      slices. Data along the helix can be obtained with a very low acquisition dose.

PMID- 17183132
TI  - Respiratory motion correction for PET oncology applications using affine
      transformation of list mode data.
AB  - Respiratory motion is a source of artefacts and reduced image quality in PET.
      Proposed methodology for correction of respiratory effects involves the use of
      gated frames, which are however of low signal-to-noise ratio. Therefore a method
      accounting for respiratory motion effects without affecting the statistical
      quality of the reconstructed images is necessary. We have implemented an affine
      transformation of list mode data for the correction of respiratory motion over
      the thorax. The study was performed using datasets of the NCAT phantom at
      different points throughout the respiratory cycle. List mode data based PET
      simulated frames were produced by combining the NCAT datasets with a Monte Carlo
      simulation. Transformation parameters accounting for respiratory motion were
      estimated according to an affine registration and were subsequently applied on
      the original list mode data. The corrected and uncorrected list mode datasets
      were subsequently reconstructed using the one-pass list mode EM (OPL-EM)
      algorithm. Comparison of corrected and uncorrected respiratory motion average
      frames suggests that an affine transformation in the list mode data prior to
      reconstruction can produce significant improvements in accounting for respiratory
      motion artefacts in the lungs and heart. However, the application of a common set
      of transformation parameters across the imaging field of view does not
      significantly correct the respiratory effects on organs such as the stomach,
      liver or spleen.

PMID- 17183133
TI  - Quantitative spatially resolved measurement of tissue chromophore concentrations
      using photoacoustic spectroscopy: application to the measurement of blood
      oxygenation and haemoglobin concentration.
AB  - A new approach based on pulsed photoacoustic spectroscopy for non-invasively
      quantifying tissue chromophore concentrations with high spatial resolution has
      been developed. The technique is applicable to the quantification of tissue
      chromophores such as oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) for the
      measurement of physiological parameters such as blood oxygen saturation (SO(2))
      and total haemoglobin concentration. It can also be used to quantify the local
      accumulation of targeted contrast agents used in photoacoustic molecular imaging.
      The technique employs a model-based inversion scheme to recover the chromophore
      concentrations from photoacoustic measurements. This comprises a numerical
      forward model of the detected time-dependent photoacoustic signal that
      incorporates a multiwavelength diffusion-based finite element light propagation
      model to describe the light transport and a time-domain acoustic model to
      describe the generation, propagation and detection of the photoacoustic wave. The
      forward model is then inverted by iteratively fitting it to measurements of
      photoacoustic signals acquired at different wavelengths to recover the
      chromophore concentrations. To validate this approach, photoacoustic signals were
      generated in a tissue phantom using nanosecond laser pulses between 740 nm and
      1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a
      near-infrared dye in which three tubes were immersed. Blood at physiological
      haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100%
      was circulated through the tubes. The signal amplitude from different temporal
      sections of the detected photoacoustic waveforms was plotted as a function of
      wavelength and the forward model fitted to these data to recover the
      concentrations of HbO(2) and HHb, total haemoglobin concentration and SO(2). The
      performance was found to compare favourably to that of a laboratory CO-oximeter
      with measurement resolutions of +/-3.8 g l(-1) (+/-58 microM) and +/-4.4 g l(-1)
      (+/-68 microM) for the HbO(2) and HHb concentrations respectively and +/-4% for
      SO(2) with an accuracy in the latter in the range -6%-+7%.

PMID- 17183134
TI  - Influence of the linac design on intensity-modulated radiotherapy of head-and
      neck plans.
AB  - In this study, we quantify the impact of linac/MLC design parameters on IMRT
      treatment plans. The investigated parameters were leaf width in the MLC, leaf
      transmission, related to the thickness of the leaves, and penumbra related
      primarily to the source size. Seven head-and-neck patients with stage T1-T3N0
      N2cM0 oropharyngeal cancer were studied. For each patient nine plans were made
      with a different set of linac/MLC parameters. The plans were optimized in
      Pinnacle(3) v7.6c and PLATO RTS v2.6.4, ITP v1.1.8. A hypothetical ideal
      linac/MLC was introduced to investigate the influence of one parameter at a time
      without interaction of other parameters. When any of the three parameters was
      increased from the ideal set-up values (leaf width 2.5 mm, transmission 0%,
      penumbra 3 mm), the mean dose to the parotid glands increased, given the same
      tumour coverage. The largest increase was found for increasing leaf transmission.
      The investigation showed that by changing more than one parameter of the ideal
      linac/MLC set-up, the increase in the mean dose was smaller than the sum of dose
      increments for each parameter separately. As a reference to clinical practice, we
      also optimized the plans of the seven patients with the clinically used Elekta
      SLi 15, equipped with a standard MLC with a leaf width of 10 mm. As compared to
      the ideal linac, this resulted in an increase of the average dose to the parotid
      glands of 5.8 Gy.

PMID- 17183135
TI  - Dual-energy cardiac imaging: an image quality and dose comparison for a flat
      panel detector and x-ray image intensifier.
AB  - This study presents a comparison of dual-energy imaging with an x-ray image
      intensifier and flat-panel detector for cardiac imaging. It also investigates if
      the wide dynamic range of the flat-panel detector can improve dual-energy image
      quality while reducing patient dose. Experimental contrast-to-noise (CNR)
      measurements were carried out in addition to simulation studies. Patient entrance
      exposure and system tube loading were also recorded. The studied contrast objects
      were calcium and iodine. System performance was quantified with a figure-of-merit
      (FOM) defined as the image CNR(2) over patient entrance exposure. The range of
      thickness studied was from 10 to 30 cm of Lucite (PMMA). Detector dose was
      initially set to 140 nGy (16 microR)/frame. The high-energy 120 kVp beam was
      filtered by an additional 0.8 mm silver filter. Keeping the same filament
      current, the kVp for the low-energy beam was adjusted as a function of thickness
      until 140 nGy was achieved. System performance was found to be similar for both
      systems, with the x-ray image intensifier performing better at lower thicknesses
      and the flat-panel detector performing better at higher thicknesses. This
      requirement of fixed detector entrance exposure was then relaxed and the kVp for
      the low-energy beam was allowed to vary while the mAs of the x-ray tube remained
      fixed to study changes in dual-energy image quality, patient dose and FOM with
      the flat-panel detector. It was found that as the kVp for the low-energy beam was
      reduced, system performance would rise until reaching a maximum while
      simultaneously lowering patient exposure. Suggested recommendations for optimal
      dual-energy imaging implementation are also provided.

PMID- 17183136
TI  - Polyurethane unicondylar knee prostheses: simulator wear tests and lubrication
      studies.
AB  - Many materials are used as artificial joint bearing surfaces; these include
      conventional stainless steel or CoCrMo-on-ultra-high molecular weight
      polyethylene (UHMWPE), CoCrMo on itself and alumina-on-alumina. However, these
      joints have a limited lifespan resulting in failure of the prosthesis and the
      need for revision surgery. A number of materials have been introduced recently in
      an attempt to overcome these problems. Polycarbonate urethane (PU) is a compliant
      material that can be used as an artificial joint bearing surface which has been
      developed to mimic the natural synovial joint more accurately by promoting fluid
      film lubrication. Tribological tests were performed on CoCrMo-on-PU unicondylar
      knee prostheses to assess their performance in vitro. The wear produced by these
      components was considerably lower than that found for conventional joints. They
      also exhibited low friction and operated close to full-fluid film lubrication
      with viscosities of lubricant similar to those found in patients with arthritis.
      These tests gave encouraging results for the tribological performance of this
      material couple for use as an alternative bearing combination.

PMID- 17183137
TI  - Evaluation of static physics performance of the jPET-D4 by Monte Carlo
      simulations.
AB  - The jPET-D4 is the first PET scanner to introduce a unique four-layer depth-of
      interaction (DOI) detector scheme in order to achieve high sensitivity and
      uniform high spatial resolution. This paper compares measurement and Monte Carlo
      simulation results of the static physics performance of this prototype research
      PET scanner. Measurement results include single and coincidence energy spectra,
      point and line source sensitivities, axial sensitivity profile (slice profile)
      and scatter fraction. We use GATE (Geant4 application for tomographic emission)
      as a Monte Carlo radiation transport model. Experimental results are reproduced
      well by the simulation model with reasonable assumptions on characteristic
      responses of the DOI detectors. In a previous study, the jPET-D4 was shown to
      provide a uniform spatial resolution as good as 3 mm (FHWM). In the present
      study, we demonstrate that a high sensitivity, 11.3 +/- 0.5%, is provided at the
      FOV centre. However, about three-fourths of this sensitivity is related to
      multiple-crystal events, for which some misidentification of the crystal cannot
      be avoided. Therefore, it is crucial to develop a more efficient way to identify
      the crystal of interaction and to reduce misidentification in order to make use
      of these high performance values simultaneously. We expect that effective
      sensitivity can be improved by replacing the GSO crystals with more absorptive
      crystals such as BGO and LSO. The results we describe here are essential to take
      full advantage of the next generation PET systems that have DOI recognition
      capability.

PMID- 17183138
TI  - Precautions and strategies in using a commercial flatbed scanner for radiochromic
      film dosimetry.
AB  - The purpose of this study was to investigate the value of a commercially
      available flatbed scanner for film dosimetry with radiochromic film for external
      radiotherapy. The EPSON Pro 1680 Expression scanner was examined as a
      densitometer for two-dimensional film dosimetry with Gafchromic EBT film. An
      accurate and efficient scanning procedure was established. Possible drift and
      warm-up effects of the scanner were studied and the direct physical influence of
      the scanner light on the radiochromic film was assessed. Next, we investigated
      the scan field uniformity. Also, we examined if the accuracy of radiochromic film
      was improved by subtracting the optical density of the unirradiated blank film
      from the optical density of the irradiated film. To assess the accuracy of
      Gafchromic EBT film when the EPSON scanner was used as a densitometer, the depth
      dose of a 2 x 15 cm(2) field and the in-plane and cross-plane profiles of a 15 x
      15 cm(2) field were measured and compared with diamond detector measurements.
      When taking consecutive scans, we found that the optical density taken from the
      first scan was about 1% higher than the optical density taken from subsequent
      scans. We attribute this to the warming up of the lamp of the scanner. Longer
      term drift of the scanner was found to be absent. We found that the use of a
      correction matrix was necessary to correct for the non-uniform scanner response
      over the scan field. Subtracting the optical density of the unirradiated blank
      film from the irradiated film improves the precision of the Gafchromic EBT film.
      Depth dose and profile measurements with Gafchromic EBT film and the diamond
      detector are in agreement within 2.5%. The EPSON Pro 1680 Expression scanner is
      an excellent tool for accurate two-dimensional film dosimetry with Gafchromic EBT
      film provided that some precautions and corrections are taken into account.

PMID- 17183139
TI  - A motion phantom study on helical tomotherapy: the dosimetric impacts of delivery
      technique and motion.
AB  - Helical tomotherapy (HT) can potentially be used for lung cancer treatment
      including stereotactic radiosurgery because of its advanced image guidance and
      its ability to deliver highly conformal dose distributions. However, previous
      theoretical and simulation studies reported that the effect of respiratory motion
      on statically planned tomotherapy treatments may cause substantial differences
      between the calculated and actual delivered radiation isodose distribution,
      particularly when the treatment is hypofractionated. In order to determine the
      dosimetric effects of motion upon actual HT treatment delivery, phantom film
      dosimetry measurements were performed under static and moving conditions using a
      clinical HT treatment unit. The motion phantom system was constructed using a
      programmable motor, a base, a moving platform and a life size lung heterogeneity
      phantom with wood inserts representing lung tissue with a 3.0 cm diameter
      spherical tumour density equivalent insert. In order to determine the effects of
      different motion and tomotherapy delivery parameters, treatment plans were
      created using jaw sizes of 1.04 cm and 2.47 cm, with incremental gantry rotation
      periods between the minimum allowed (10 s) and the maximum allowed (60 s). The
      couch speed varied from 0.009 cm s(-1) to 0.049 cm s(-1), and delivered to a
      phantom under static and dynamic conditions with peak-to-peak motion amplitudes
      of 1.2 cm and 2 cm and periods of 3 and 5 s to simulate human respiratory motion
      of lung tumours. A cylindrical clinical target volume (CTV) was contoured to
      tightly enclose the tumour insert. 2.0 Gy was prescribed to 95% of the CTV. Two
      dimensional dose was measured by a Kodak EDR2 film. Dynamic phantom doses were
      then quantitatively compared to static phantom doses in terms of axial dose
      profiles, cumulative dose volume histograms (DVH), percentage of CTV receiving
      the prescription dose and the minimum dose received by 95% of the CTV. The larger
      motion amplitude resulted in more under-dosing at the ends of the CTV in the axis
      of motion, and this effect was greater for the smaller jaw size plans. Due to the
      size of the penumbra, the 2.47 cm jaw plans provide adequate coverage for smaller
      amplitudes of motion, +/-0.6 cm in our experiment, without adding any additional
      margin in the axis of motion to the treatment volume. The periodic heterogeneous
      patterns described by previous studies were not observed from the single fraction
      of the phantom measurement. Besides the jaw sizes, CTV dose coverage is not
      significantly dependent on machine and phantom motion periods. The lack of
      adverse synchronization patterns from both results validate that HT is a safe
      technique for treating moving target and hypofractionation.

PMID- 17183140
TI  - Population and patient-specific target margins for 4D adaptive radiotherapy to
      account for intra- and inter-fraction variation in lung tumour position.
AB  - In this work, five 4D image-guidance strategies (two population, an offline
      adaptive and two online strategies) were evaluated that compensated for both
      inter- and intra-fraction variability such as changes to the baseline tumour
      position and respiratory pattern. None of the strategies required active motion
      compensation such as gating or tracking; all strategies simulated a free
      breathing-based treatment technique. Online kilovoltage fluoroscopy was acquired
      for eight patients with lung tumours, and used to construct inter- and intra
      fraction tumour position variability models. Planning was performed on a mid
      ventilation image acquired from a respiration-correlated CT scan. The blurring
      effect of tumour position variability was included in the dose calculation by
      convolution. CTV to PTV margins were calculated for variability in the cranio
      caudal direction. A population margin of 9.0 +/- 0.7 mm was required to account
      for setup error and respiration in the study population without the use of image
      guidance. The greatest mean margin reduction was introduced by the offline
      adaptive strategy. A daily online correction strategy produced a small reduction
      (1.6 mm) in the mean margin from the offline strategy. Adaptively correcting for
      an inter-fraction change in the respiratory pattern had little effect on margin
      size due to most patients having only small daily changes in the respiratory
      pattern. A daily online correction strategy would be useful for patients who
      exhibit large variations in the daily mean tumour position, while an offline
      adaptive strategy is more applicable to patients with less variation.

PMID- 17183141
TI  - Comparison of rectal dose histograms under conditions of nonlinear isodoses.
AB  - Cumulative dose-volume histograms of organs-at-risk are commonly used as
      predictors of the likelihood and severity of toxicity. In the case of hollow
      organs such as the rectum, the dose-volume histogram of the organ disregarding
      the lumen (dose-wall histogram, DWH) can be difficult to outline, and where the
      voxel size approaches the wall thickness, poor dose statistics can result.
      Various surrogates for DWH have been proposed, including the dose-volume
      histogram of organ plus the lumen (DVH), the dose-surface histogram (DSH), the
      normalized dose-volume histogram of organ plus lumen (NDVH) and the normalized
      dose-surface histogram (NDSH). In order to test the relative relationships
      between these histogram types in the case of prostate radiotherapy, a cylindrical
      model of the rectum has been combined with an idealized nonlinear isodose model
      in order to allow typical isodose shapes from both conventional three-field
      radiotherapy and prostate IMRT to be studied. Analytic expressions for histogram
      values are derived, and implemented through a spreadsheet. Isodose shapes and
      positions from five patients are combined to generate typical isodose
      distributions for which histograms may be generated and compared. It is found
      that the plan type has little effect on the relative values of the histogram
      points, and that no other histogram acts as a robust estimate of the DWH under
      all conditions. However, if the irradiated portion of the rectum is empty, NDVH
      is a good surrogate for DWH.

PMID- 17183142
TI  - Optimum parameters in a model for tumour control probability, including
      interpatient heterogeneity: evaluation of the log-normal distribution.
AB  - The heterogeneity of human tumour radiation response is well known. Researchers
      have used the normal distribution to describe interpatient tumour
      radiosensitivity. However, many natural phenomena show a log-normal distribution.
      Log-normal distributions are common when mean values are low, variances are large
      and values cannot be negative. These conditions apply to radiosensitivity. The
      aim of this work was to evaluate the log-normal distribution to predict clinical
      tumour control probability (TCP) data and to compare the results with the
      homogeneous (delta-function with single alpha-value) and normal distributions.
      The clinically derived TCP data for four tumour types-melanoma, breast, squamous
      cell carcinoma and nodes-were used to fit the TCP models. Three forms of
      interpatient tumour radiosensitivity were considered: the log-normal, normal and
      delta-function. The free parameters in the models were the radiosensitivity mean,
      standard deviation and clonogenic cell density. The evaluation metric was the
      deviance of the maximum likelihood estimation of the fit of the TCP calculated
      using the predicted parameters to the clinical data. We conclude that (1) the log
      normal and normal distributions of interpatient tumour radiosensitivity
      heterogeneity more closely describe clinical TCP data than a single
      radiosensitivity value and (2) the log-normal distribution has some theoretical
      and practical advantages over the normal distribution. Further work is needed to
      test these models on higher quality clinical outcome datasets.

PMID- 17183143
TI  - Monte Carlo simulation of MOSFET detectors for high-energy photon beams using the
      PENELOPE code.
AB  - The aim of this work was the Monte Carlo (MC) simulation of the response of
      commercially available dosimeters based on metal oxide semiconductor field effect
      transistors (MOSFETs) for radiotherapeutic photon beams using the PENELOPE code.
      The studied Thomson&Nielsen TN-502-RD MOSFETs have a very small sensitive area of
      0.04 mm(2) and a thickness of 0.5 microm which is placed on a flat kapton base
      and covered by a rounded layer of black epoxy resin. The influence of different
      metallic and Plastic water build-up caps, together with the orientation of the
      detector have been investigated for the specific application of MOSFET detectors
      for entrance in vivo dosimetry. Additionally, the energy dependence of MOSFET
      detectors for different high-energy photon beams (with energy >1.25 MeV) has been
      calculated. Calculations were carried out for simulated 6 MV and 18 MV x-ray
      beams generated by a Varian Clinac 1800 linear accelerator, a Co-60 photon beam
      from a Theratron 780 unit, and monoenergetic photon beams ranging from 2 MeV to
      10 MeV. The results of the validation of the simulated photon beams show that the
      average difference between MC results and reference data is negligible, within
      0.3%. MC simulated results of the effect of the build-up caps on the MOSFET
      response are in good agreement with experimental measurements, within the
      uncertainties. In particular, for the 18 MV photon beam the response of the
      detectors under a tungsten cap is 48% higher than for a 2 cm Plastic water cap
      and approximately 26% higher when a brass cap is used. This effect is
      demonstrated to be caused by positron production in the build-up caps of higher
      atomic number. This work also shows that the MOSFET detectors produce a higher
      signal when their rounded side is facing the beam (up to 6%) and that there is a
      significant variation (up to 50%) in the response of the MOSFET for photon
      energies in the studied energy range. All the results have shown that the
      PENELOPE code system can successfully reproduce the response of a detector with
      such a small active area.

PMID- 17183144
TI  - Supplementation with apple juice attenuates presenilin-1 overexpression during
      dietary and genetically-induced oxidative stress.
AB  - Gain-of-function mutations in the presenilin-1 (PS-1) promote Alzheimer's disease
      (AD) by increasing reactive oxygen species, at least part of which is derived by
      an accompanying increase in generation of amyloid-beta (Abeta). Additional
      studies indicate that impaired Apolipoprotein E function, which also increases
      oxidative stress and is also associated with AD, potentiates the deleterious
      activity of PS-1. Folate deficiency is also associated with AD and potentiates
      the impact of both ApoE deficiency and beta exposure. More recently, folate
      deficiency has been shown to increase PS-1 expression. Since dietary
      supplementation with apple juice provides neuroprotection against ApoE
      deficiency, Abeta exposure and folate deficiency, we examined the impact of apple
      juice on PS-1 overexpression. Herein, we demonstrate that dietary deficiency in
      folate and vitamin E increased PS-1 expression in juvenile and adult normal
      C57B1/6J and ApoE-/- mice and in aged normal mice. Supplementation with apple
      juice concentrate (AJC) attenuated or prevent these increases. Prior studies
      demonstrate that impaired DNA methylation resulting from a deficiency in S
      adenosylmethionine (SAM, which is rapidly depleted following folate deprivation)
      leads to PS-1 overexpression, and that direct supplementation with SAM attenuates
      PS-1 overexpression. We determined that AJC contained levels of SAM comparable to
      those capable of suppressing PS-1 overexpression, suggesting that the SAM content
      of AJC represents a potential mechanism for preventing PS-1 overexpression, and
      further highlighting the possibility that AJC provides neuroprotection by
      mechanisms in addition to its antioxidant potential.

PMID- 17183145
TI  - Where the actions of environment (nutrition), gene and protein meet: beneficial
      role of fruit and vegetable juices in potentially delaying the onset of
      Alzheimer's disease.

PMID- 17183147
TI  - Apolipoprotein A-V gene polymorphism -1131T>C and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder in the
      elderly and is also considered a progeroid genetic syndrome. The etiology of AD
      is complex and the mechanisms underlying its pathophysiology remain to be
      clarified. It has been suggested that a high serum cholesterol level is a risk
      factor for (AD), and that some polymorphisms of genes encoding proteins
      regulating cholesterol metabolism are associated with AD development. APOA5 is a
      recently discovered apolipoprotein involved primarily with triglyceride (TG)
      metabolism disorder. This study investigates the association of AD with the APOA5
      gene -1131T>C polymorphisms in samples of 106 patients with Alzheimer's disease
      (AD), 76 elderly healthy controls and 93 young healthy controls. DNA samples were
      isolated from blood cells, amplified by PCR and digested with Tru1l. We observed
      that the genotype distributions of APOA5 variants were within Hardy-Weinberg
      equilibrium in all subject samples. Furthermore, chi-square test comparison for
      genotype distributions and allele frequencies did not reveal any significant
      difference among the three groups of subjects P>0.05). These results support the
      idea that these variants are not involved as a risk factor for developing AD.

PMID- 17183148
TI  - No evidence for allelic association of serotonin 2A receptor and transporter gene
      polymorphisms with depression in Alzheimer disease.
AB  - Patients with Alzheimer disease (AD) often exhibit psychiatric symptoms
      associated with cognitive impairment. The serotoninergic system may be involved
      in the development of depressive symptoms in AD patients, as suggested by the
      evidence that antidepressant drugs having the serotonin transporter as their
      target are effectively used to treat depressive AD patients. The aim of this
      study was to investigate the role of serotonin in depression, searching for
      association of two serotoninergic polymorphisms (T102C of serotonin receptor 5
      HT2A and serotonin transporter linked polymorphic region -5-HTTLPR- of SLC6A4
      gene) with depressive symptoms and considering their possible interactions with
      Apolipoprotein E (ApoE) and between themselves, in a sample of 208 sporadic AD
      patients and 116 normal controls from Italy. 5-HTTLPR and T102C are not
      associated with AD when separately analysed. However, we found out an interaction
      between the two polymorphisms in L/L and C/C genotype carriers increasing the
      risk for the disease (p=0.015, OR=8.048; 95% CI: 1.497-43.262). No association of
      the polymorphisms was detected with depression linked to AD. No interaction
      between 5-HTTLPR and T102C was detected in depressive AD subjects, even after
      stratification according to the presence of ApoE4 allele. These results suggest
      that the serotoninergic system may be not involved in the pathogenesis of
      depressive symptoms in AD patients, and it may be involved in other aspects of
      disease pathophysiology like cognitive symptoms and psychosis.

PMID- 17183150
TI  - Redox proteomics identification of oxidatively modified brain proteins in
      inherited Alzheimer's disease: an initial assessment.
AB  - OBJECTIVE: To identify oxidatively modified proteins in brains of persons with
      inherited Alzheimer's disease. METHODS: Redox proteomics was used to identify
      oxidatively modified brain proteins in persons with mutations in the genes for
      presenilin-1 (PS-1). RESULTS: An initial redox proteomics assessment of
      oxidatively modified proteins from brains of individuals with PS-1 mutations was
      performed. These PS1 mutations, Q222H and M233T, are completely penetrant causing
      early-onset familial AD as previously reported in these Australian families. We
      show that oxidative modifications of ubiquitin carboxyl-terminal hydrolase L1
      (UCH-L1), gamma-enolase, actin, and dimethylarginine dimethylaminohydrolase 1
      (DMDMAH-1) are present in the brain of familial AD subjects. CONCLUSIONS: These
      initial results suggest that oxidatively modified proteins are important common
      features in both familial and sporadic AD.

PMID- 17183149
TI  - An antibody to the beta-secretase cleavage site on amyloid-beta-protein precursor
      inhibits amyloid-beta production.
AB  - Proteolytic cleavage of amyloid-beta-protein precursor (AbetaPP) by beta- and
      gamma-secretases results in production of the amyloid-beta peptide (Abeta) that
      accumulates in the brains of sufferers of Alzheimer's disease (AD). We have
      developed a monoclonal antibody, 2B12, which binds in the vicinity of the beta
      secretase cleavage site on AbetaPP but does not bind within the Abeta region. We
      hypothesised that this antibody, directed against the substrate rather than the
      enzyme, could inhibit cleavage of AbetaPP by beta-secretase via steric hindrance
      and thus reduce downstream production of Abeta. The antibody would enter cells by
      binding to AbetaPP when it is at the cell surface and then be internalised with
      the protein. We subsequently demonstrated that, after addition of 2B12 to
      standard growth media, this antibody was indeed capable of inhibiting Abeta40
      production in neuroblastoma and astrocytoma cells expressing native AbetaPP, as
      measured by an ELISA. This inhibition was both concentration- and time-dependent
      and was specific to 2B12. We were only able to inhibit approximately 50% of
      Abeta40 production suggesting that not all AbetaPP is trafficked to the cell
      surface. We propose that this antibody could be used as a novel, putative therapy
      for the treatment of AD.

PMID- 17183151
TI  - Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid.
AB  - BACKGROUND: Treatment with HMG-CoA reductase inhibitors ("statins") has been
      variably associated with a reduced risk of Alzheimer's disease (AD) in
      epidemiologic studies and reduced amyloid-beta (Abeta) deposition in animal
      models of AD. Putative neuroprotective effects of statins may vary in relation to
      their ability to penetrate into the central nervous system (CNS). METHODS: We
      measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of
      treatment with simvastatin (a CNS permeant statin; n=10) at 40 mg/day or
      pravastatin (a CNS impermeant statin; n=13) at 80 mg/day in hypercholesterolemic
      subjects without dementia. RESULTS: Simvastatin, but not pravastatin, reduced CSF
      levels of phospho-tau-181 (p-tau181) in all subjects. There were no differences
      in CSF levels of total tau, Abeta42, Abeta40, soluble amyloid beta protein
      precursor (sAbetaPP) alpha or beta, or F2-isoprostanes. CONCLUSIONS: Statins may
      modulate the phosphorylation of tau in humans and this effect may depend on the
      CNS availability of the statin. These results suggest another mechanism by which
      statins may act to reduce the risk of AD.

PMID- 17183152
TI  - Preservation of the blood brain barrier integrity may underlie neuroprotective
      effects of statins in Alzheimer's disease.

PMID- 17183153
TI  - Validity and reliability of surrogate information for controls in a case-control
      study on Alzheimer's disease.
AB  - This study is aimed to investigate proxy respondent's information usefulness in
      retrospective studies by comparing information obtained with a questionnaire
      (with a total of 171 items) from controls and their proxy respondents in a case
      control study on Alzheimer's disease. Kappa indices and intraclass correlation
      coefficients were calculated to assess reliability, and bias factor and mean
      differences were calculated to assess validity. Proxy respondent's personal
      features (gender, age and relationship with the index subject) were also studied.
      Kappa indices and intraclass correlation coefficients were in general good or
      very good (>0.6), specially regarding control's personal and family data (ranges
      0.45-1 for Kappa and 0.86-0.99 for intraclass correlation coefficient) and
      occupational exposures (range for Kappa 0.48-1). No systematic biases were found
      (range for bias factor 0.65-4.12 and range for mean differences -1.81-1.30, none
      of them statistically significant). Proxy respondent's individual features were
      not found to systematically affect reliability. The use of surrogate information
      for controls in etiologic case-control studies of Alzheimer's disease may be
      useful without unacceptable loss of information or systematic biases.

PMID- 17183154
TI  - Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in
      Squirrel monkeys (Saimiri sciureus).
AB  - Recent studies from our laboratories and others suggest that calorie restriction
      (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-beta (Abeta)
      neuropathology in the mouse models of AD. Moreover, we found that promotion of
      the NAD+-dependent SIRT1 mediated deacetylase activity, a key regulator in CR
      extension of life span, may be a mechanism by which CR influences AD-type
      neuropathology. In this study we continued to explore the role of CR in AD-type
      brain amyloidosis in Squirrel monkeys (Saimiri sciureus). Monkeys were maintained
      on the normal and CR diets throughout the entire lifespan until they died of
      natural causes. We found that 30% CR resulted in reduced contents of Abeta1-40
      and Abeta1-42 peptides in the temporal cortex of Squirrel monkeys, relative to
      control (CON) fed monkeys. The decreased contents of cortical Abeta peptide
      inversely correlated with SIRT1 protein concentrations in the same brain region;
      no detectable change in total full-length amyloid-beta protein precursor
      (AbetaPP) level was found. Most interestingly, we found that 30% CR resulted in a
      select elevation of alpha- but not beta- or gamma- secretase activity which
      coincided with decreased ROCK1 protein content in the same brain region, relative
      to CON group. Collectively, the study suggests that investigation of the role of
      CR in non-human primates may provide a valuable approach for further clarifying
      the role of CR in AD.

PMID- 17183155
TI  - Dopamine-induced stress signaling in COS-7 cells transfected with selectively
      vulnerable muscarinic receptor subtypes is partially mediated via the i3 loop and
      antagonized by blueberry extract.
AB  - Muscarinic receptors (MAChRs) are intimately involved in various aspects of both
      neuronal and vascular functioning, and there is selective oxidative stress
      sensitivity (OSS) among MAChR subtypes, with M1, M2, and M4 showing>OSS. OSS was
      assessed by determining the loss of ability of the cell to extrude or sequester
      Ca2+ following oxotremorine-induced depolarization following exposure to dopamine
      (DA) subtypes in transfected COS-7 cells. This OSS can be prevented by
      pretreatment with blueberry (BB) extract. Present studies were carried out to
      determine BB treatment of the cells transfected with wild type, truncated or
      chimeric [where the i3 loop of one receptor was switched with the i3 loop of the
      other; i.e., M1(M3i3) and M3(M1i3)] receptors would alter DA-induced changes in
      calcium buffering and would confer protection through alterations in pMAPK, pCREB
      or PKC signaling. These findings also suggest that BB may antagonize OS effects
      by lowering activation of pCREB and possibly PKCgamma induced by DA. In the
      truncated and chimeric receptors, results indicated that BB reduced OSS in
      response to DA in M1-transfected cells. However, BBs were also effective in
      preventing these Ca2+ buffering deficits in cells transfected with M1 receptors
      in which the i3 loop had been removed, but only partially enhanced the protective
      effects of the M3 i3 loop in the M1(M3i3) chimerics. A similar partial effect of
      BBs was seen in the M3(M1i3) chimerics which showed increased OSS in response to
      DA. It appears that antioxidants found in BBs might be targeting additional sites
      on these chimerics to decrease OSS.

PMID- 17183156
TI  - Plasma amyloid-beta, Abeta1-42, load is reduced by haemodialysis.
AB  - Patients with chronic renal failure treated with haemodialysis have vascular risk
      factors that, in the general population, are associated with increased prevalence
      of Alzheimer's disease (AD). Patients in haemodialysis, however, present
      different kinds of dementia but they do not have an increased risk of AD. We have
      hypothesized that amyloid-beta (Abeta)1-42 is washed out from plasma during the
      dialysis and that this procedure enhances Abeta elimination and reduces the risk
      of AD. We have measured plasma Abeta1-42 levels in 11 patients with renal
      failure, before and after haemodialysis. A single procedure reduced the plasma
      Abeta levels in all subjects with a mean decrement of 30% of baseline. Since
      Abeta deposition could be altered by certain metals like Cu and Zn, we have also
      measured the effects of dialysis on the levels of these ions in plasma. We found
      no changes in levels of Cu and Zn after dialysis. Haemodialysis, therefore,
      reduces very effectively plasma Abeta without modifying Cu and Zn levels. The
      potential use of this strategy in patients with AD requires further
      investigation.

PMID- 17183157
TI  - Voxel-based morphometry in Alzheimer's patients.

PMID- 17183159
TI  - A vexing Commentary on the important issue of aluminium and Alzheimer' disease.

PMID- 17183160
TI  - The discovery and mapping to chromosome 21 of the Alzheimer's amyloid gene:
      history revised.

PMID- 17183161
TI  - Effects of the magnesium and chloride ions and shikimate on the structure of
      shikimate kinase from Mycobacterium tuberculosis.
AB  - Bacteria, fungi and plants can convert carbohydrate and phosphoenolpyruvate into
      chorismate, which is the precursor of various aromatic compounds. The seven
      enzymes of the shikimate pathway are responsible for this conversion. Shikimate
      kinase (SK) is the fifth enzyme in this pathway and converts shikimate to
      shikimate-3-phosphate. In this work, the conformational changes that occur on
      binding of shikimate, magnesium and chloride ions to SK from Mycobacterium
      tuberculosis (MtSK) are described. It was observed that both ions and shikimate
      influence the conformation of residues of the active site of MtSK. Magnesium
      influences the conformation of the shikimate hydroxyl groups and the position of
      the side chains of some of the residues of the active site. Chloride seems to
      influence the affinity of ADP and its position in the active site and the opening
      length of the LID domain. Shikimate binding causes a closing of the LID domain
      and also seems to influence the crystallographic packing of SK. The results shown
      here could be useful for understanding the catalytic mechanism of SK and the role
      of ions in the activity of this protein.

PMID- 17183162
TI  - Structure of the catalytic domain of the hyperthermophilic chitinase from
      Pyrococcus furiosus.
AB  - The crystal structure of the catalytic domain of a chitinase from the
      hyperthermophilic archaeon Pyrococcus furiosus (AD2(PF-ChiA)) has been determined
      at 1.5 A resolution. This is the first structure of the catalytic domain of an
      archaeal chitinase. The overall structure of AD2(PF-ChiA) is a TIM-barrel fold
      with a tunnel-like active site that is a common feature of family 18 chitinases.
      Although the catalytic residues (Asp522, Asp524 and Glu526) are conserved,
      comparison of the conserved residues and structures with those of other
      homologous chitinases indicates that the catalytic mechanism of PF-ChiA is
      different from that of family 18 chitinases.

PMID- 17183163
TI  - Purification, crystallization and preliminary X-ray analysis of the BseCI DNA
      methyltransferase from Bacillus stearothermophilus in complex with its cognate
      DNA.
AB  - The DNA methyltransferase M.BseCI from Bacillus stearothermophilus (EC 2.1.1.72),
      a 579-amino-acid enzyme, methylates the N6 atom of the 3' adenine in the sequence
      5'-ATCGAT-3'. M.BseCI was crystallized in complex with its cognate DNA. The
      crystals were found to belong to the hexagonal space group P6, with unit-cell
      parameters a = b = 87.0, c = 156.1 A, beta = 120.0 degrees and one molecule in
      the asymmetric unit. Two complete data sets were collected at wavelengths of 1.1
      and 2.0 A to 2.5 and 2.8 A resolution, respectively, using synchrotron radiation
      at 100 K.

PMID- 17183164
TI  - Purification, crystallization and preliminary crystallographic analysis of
      archaeal 6-pyruvoyl tetrahydrobiopterin synthase homologue PH0634 from Pyrococcus
      horikoshii OT3.
AB  - 6-Pyruvoyl tetrahydrobiopterin synthase (PTPS) catalyses the conversion of
      dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, the second of the
      three enzymatic steps in the synthesis of tetrahydrobiopterin from GTP. PH0634, a
      13.51 kDa archaeal PTPS homologue from Pyrococcus horikoshii OT3, was
      overexpressed as native and selenomethionine-substituted protein and the purified
      protein was crystallized by the oil-microbatch method at 295 K. X-ray diffraction
      data were collected to 2.1 A resolution from the native crystal using synchrotron
      radiation at 100 K. The crystal belongs to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 35.83, b = 95.71, c = 105.65 A.
      Threefold noncrystallographic symmetry was identified from self-rotation
      calculations. Assuming the presence of a trimer in the asymmetric unit, the
      solvent content is 45% (V(M) = 2.24 A3 Da(-1)). The selenomethionine-substituted
      crystal is isomorphous to the native crystal and diffracts X-rays to 2.9 A.

PMID- 17183165
TI  - Expression, purification and preliminary crystallographic studies on the
      catalytic region of the nonreceptor tyrosine kinase Fes.
AB  - The proto-oncogene tyrosine protein kinase c-fps/fes encodes a structurally
      unique protein (Fes) of the nonreceptor protein-tyrosine kinase (PTK) family. Its
      expression has been demonstrated in myeloid haematopoietic cells, vascular
      endothelial cells and in neurons. In human-derived and murine-derived cell lines,
      the activated form of this kinase can induce cellular transformation; moreover,
      it has been shown that Fes is involved in the regulation of cell-cell and cell
      matrix interactions mediated by adherens junctions and focal adhesions. The N
      terminus of Fes contains the FCH (Fps/Fes/Fer/CIP4 homology) domain, which is
      unique to the Fes/Fer kinase family. It is followed by three coiled-coil domains
      and an SH2 (Src-homology 2) domain. The catalytic region (Fes-CR) is located at
      the C-terminus of the protein. The successful expression, purification and
      crystallization of the catalytic part of Fes (Fes-CR) are described.

PMID- 17183166
TI  - Purification, crystallization and preliminary crystallographic characterization
      of the caspase-recruitment domain of human Nod1.
AB  - The caspase-recruitment domain (CARD) is known to play an important role in
      apoptosis and inflammation as an essential protein-protein interaction domain.
      The CARD of the cytosolic pathogen receptor Nod1 was overexpressed in Escherichia
      coli and purified by affinity chromatography and gel filtration. The purified
      CARD was crystallized at 277 K using the microseeding method. X-ray diffraction
      data were collected to 1.9 A resolution. The crystals belong to space group P3(1)
      or P3(2), with unit-cell parameters a = b = 79.1, c = 80.9 A. Preliminary
      analysis indicates that there is one dimeric CARD molecule in the asymmetric
      unit.

PMID- 17183167
TI  - Preliminary crystallographic analysis of avian infectious bronchitis virus main
      protease.
AB  - Infectious bronchitis virus (IBV) is the prototype of the genus Coronavirus. It
      causes a highly contagious disease which affects the respiratory, reproductive,
      neurological and renal systems of chickens, resulting great economic losses in
      the poultry industry worldwide. The coronavirus (CoV) main protease (M(pro)),
      which plays a pivotal role in viral gene expression and replication through a
      highly complex cascade involving the proteolytic processing of replicase
      polyproteins, is an attractive target for antiviral drug design. In this study,
      IBV M(pro) was overexpressed in Escherichia coli. Crystals suitable for X-ray
      crystallography have been obtained using microseeding techniques and belong to
      space group P6(1)22. X-ray diffraction data were collected in-house to 2.7 A
      resolution from a single crystal. The unit-cell parameters were a = b = 119.1, c
      = 270.7 A, alpha = beta = 90, gamma = 120 degrees. Three molecules were predicted
      to be present in the asymmetric unit from a calculated self-rotation function.

PMID- 17183169
TI  - Preliminary X-ray analysis of XC5848, a hypothetical ORFan protein with an Sm
      like motif from Xanthomonas campestris.
AB  - XC5848, a hypothetical protein from the pathogenic bacterium Xanthomonas
      campestris that causes black rot, has been chosen as a potential target for the
      discovery of novel folds. It is unique to the Xanthomonas genus and has
      significant sequence identity mainly to corresponding proteins from the
      Xanthomonas genus. In this paper, the cloning, overexpression, purification and
      crystallization of the XC5848 protein are reported. The XC5848 crystals
      diffracted to a resolution of at least 1.68 A. They belong to the orthorhombic
      space group P2(1)2(1)2(1), with unit-cell parameters a = 48.13, b = 51.62, c =
      82.32 A. Two molecules were found in each asymmetric unit. Preliminary structural
      studies nevertheless indicate that XC5848 belongs to the highly conserved Sm-like
      alpha-beta-beta-beta-beta fold. However, significant differences in sequence and
      structure were observed. It therefore represents a novel variant of the crucial
      Sm-like motif that is heavily involved in mRNA splicing and degradation.

PMID- 17183168
TI  - Crystallization and preliminary crystallographic analysis of molybdenum-cofactor
      biosynthesis protein C from Thermus thermophilus.
AB  - The gram-negative aerobic eubacterium Thermus thermophilus is an extremely
      important thermophilic microorganism that was originally isolated from a thermal
      vent environment in Japan. The molybdenum cofactor in this organism is considered
      to be an essential component required by enzymes that catalyze diverse key
      reactions in the global metabolism of carbon, nitrogen and sulfur. The molybdenum
      cofactor biosynthesis protein C derived from T. thermophilus was crystallized in
      two different space groups. Crystals obtained using the first crystallization
      condition belong to the monoclinic space group P2(1), with unit-cell parameters a
      = 64.81, b = 109.84, c = 115.19 A, beta = 104.9 degrees; the crystal diffracted
      to a resolution of 1.9 A. The other crystal form belonged to space group R32,
      with unit-cell parameters a = b = 106.57, c = 59.25 A, and diffracted to 1.75 A
      resolution. Preliminary calculations reveal that the asymmetric unit contains 12
      monomers and one monomer for the crystals belonging to space group P2(1) and R32,
      respectively.

PMID- 17183170
TI  - Preliminary structural studies of the transcriptional regulator CmeR from
      Campylobacter jejuni.
AB  - In Campylobacter jejuni, a gram-negative bacterial pathogen causing
      gastroenteritis in humans, the CmeR regulatory protein controls transcription of
      the multidrug transporter gene operon cmeABC. CmeR belongs to the TetR family of
      transcriptional regulators. The 210-residue CmeR consists of two functional
      motifs: an N-terminal DNA-binding domain and a C-terminal ligand-binding domain.
      It is predicted that the DNA-binding domain interacts directly with target
      promoters, while the C-terminal motif interacts with inducing ligands (such as
      bile salts). As an initial step towards confirming this structural model,
      recombinant CmeR protein containing a 6 x His tag at the N-terminus was
      crystallized. Crystals of ligand-free CmeR belonged to space group P2(1)2(1)2,
      with unit-cell parameters a = 37.4, b = 57.6, c = 93.3 A. Diffraction was
      observed to at least 2.2 A at 100 K. Analysis of the detailed CmeR structure is
      currently in progress.

PMID- 17183171
TI  - Preliminary X-ray diffraction analysis of YcdB from Escherichia coli: a novel
      haem-containing and Tat-secreted periplasmic protein with a potential role in
      iron transport.
AB  - YcdB is a periplasmic haem-containing protein from Escherichia coli that has a
      potential role in iron transport. It is currently the only reported haem
      containing Tat-secreted substrate. Here, the overexpression, purification,
      crystallization and structure determination at 2.0 A resolution are reported for
      the apo form of the protein. The apo-YcdB structure resembles those of members of
      the haem-dependent peroxidase family and thus confirms that YcdB is also a member
      of this family. Haem-soaking experiments with preformed apo-YcdB crystals have
      been optimized to successfully generate haem-containing YcdB crystals that
      diffract to 2.9 A. Completion of model building and structure refinement are
      under way.

PMID- 17183172
TI  - Preliminary time-of-flight neutron diffraction study on diisopropyl
      fluorophosphatase (DFPase) from Loligo vulgaris.
AB  - The enzyme diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris is capable
      of decontaminating a wide variety of toxic organophosphorus nerve agents. DFPase
      is structurally related to a number of enzymes, such as the medically important
      paraoxonase (PON). In order to investigate the reaction mechanism of this
      phosphotriesterase and to elucidate the protonation state of the active-site
      residues, large-sized crystals of DFPase have been prepared for neutron
      diffraction studies. Available H atoms have been exchanged through vapour
      diffusion against D2O-containing mother liquor in the capillary. A neutron data
      set has been collected to 2.2 A resolution on a relatively small (0.43 mm3)
      crystal at the spallation source in Los Alamos. The sample size and asymmetric
      unit requirements for the feasibility of neutron diffraction studies are
      summarized.

PMID- 17183173
TI  - Crystallization and preliminary X-ray diffraction analysis of an Escherichia coli
      tRNA(Gly) acceptor-stem microhelix.
AB  - The tRNA(Gly) and glycyl-tRNA synthetase (GlyRS) system is an evolutionary
      special case within the class II aminoacyl-tRNA synthetases because two divergent
      types of GlyRS exist: an archaebacterial/human type and an eubacterial type. The
      tRNA identity elements which determine the correct aminoacylation process are
      located in the aminoacyl domain of tRNA(Gly). To obtain further insight
      concerning structural investigation of the identity elements, the Escherichia
      coli seven-base-pair tRNA(Gly) acceptor-stem helix was crystallized. Data were
      collected to 2.0 A resolution using synchrotron radiation. Crystals belong to
      space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 35.35, c =
      130.82 A, alpha = beta = 90, gamma = 120 degrees and two molecules in the
      asymmetric unit.

PMID- 17183175
TI  - Exploration of triple-helical fragments: crystallization and preliminary X-ray
      diffraction of d(TGGCCTTAAGG).
AB  - The nonamer d(GCGAATTCG) and decamer d(GGCCAATTGG), containing one and two
      overhanging guanines, respectively, form G x GC triplets in their crystal
      packing. In order to introduce a third subsequent T x AT triplet, the decamer was
      further extended by one overhanging thymine residue. Two different crystal
      morphologies of the sequence d(TGGCCTTAAGG) were obtained by hanging-drop vapour
      diffusion and diffracted to 2.5 and 2.3 A resolution, respectively. However, both
      crystals belong to the orthorhombic space group P2(1)2(1)2(1), with similar unit
      cell parameters. Therefore, the two data sets could be merged to a resolution of
      2.4 A with unit-cell parameters a = 26.97, b = 41.12, c = 52.72 A.

PMID- 17183174
TI  - Crystallographic characterization of the radixin FERM domain bound to the
      cytoplasmic tails of adhesion molecules CD43 and PSGL-1.
AB  - Radixin is a member of the ERM proteins that cross-link plasma membranes and
      actin filaments. The FERM domains located in the N-terminal regions of ERM
      proteins are responsible for membrane association through direct interaction with
      the cytoplasmic tails of integral membrane proteins. Here, crystals of the
      radixin FERM domain bound to the cytoplasmic peptides of two adhesion molecules,
      CD43 and PSGL-1, have been obtained. Crystals of the radixin FERM domain bound to
      CD43 belong to space group P4(3)22, with unit-cell parameters a = b = 68.72, c =
      201.39 A, and contain one complex in the crystallographic asymmetric unit.
      Crystals of the radixin FERM domain bound to PSGL-1 belong to space group
      P2(1)2(1)2(1), with unit-cell parameters a = 80.74, b = 85.73, c = 117.75 A, and
      contain two complexes in the crystallographic asymmetric unit. Intensity data
      sets were collected to a resolution of 2.9 A for the FERM-CD43 complex and 2.8 A
      for the FERM-PSGL-1 complex.

PMID- 17183176
TI  - Purification, crystallization and preliminary crystallographic analysis of the
      putative thiamine-biosynthesis protein PH1313 from Pyrococcus horikoshii OT3.
AB  - The putative thiamine-biosynthesis protein PH1313 from Pyrococcus horikoshii OT3
      has been overexpressed and purified. Crystallization was performed by the oil
      microbatch method using 28%(v/v) 2-methyl-2,4-pentanediol as a precipitant at 291
      K. A native X-ray diffraction data set at 1.9 A resolution and a single anomalous
      dispersion data set from a selenomethionine-derivative crystal at 2.1 A
      resolution were collected using synchrotron radiation at 100 K. The native
      crystal belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell
      parameters a = 71.7, b = 71.2, c = 141.8 A.

PMID- 17183179
TI  - Knowledge and attitude on infant oral health among graduating medical students in
      Kerala.
AB  - Providing dental and oral health care to all children in Kerala remains a thorny
      challenge. Lack of community water fluoridation, dental workforce shortages and
      geographical barriers all aggravate oral health and access problems. Children
      from low-income and minority families and children with special needs are at
      particular risk. Family centered disease prevention strategies are needed to
      reduce oral health disparities in children. Oral health promotion can take place
      in a primary care practitioner's office, but medical providers often lack
      relevant training. Present study was conducted to evaluate knowledge and attitude
      of graduating medical students towards infant oral health qualitative methods
      were used to evaluate the program.

PMID- 17183180
TI  - Early childhood caries and dental plaque among 1-3-year-olds in Tehran, Iran.
AB  - The association between plaque and caries in older children and adults has been
      poor, however, some studies show that there may be a relationship in younger
      children. The aim was to study the relationships between dental caries and dental
      plaque among 12-36-month-olds in Tehran, Iran. A cross-sectional study among a
      stratified random sample of 504 children aged one to three years from 18 public
      health centres in Tehran. Mothers were interviewed about their child's date and
      order of birth, gender, primary caregiver, the mother's age and the educational
      level of both parents. Dental examination was carried out according to the WHO
      criteria. Early childhood caries (ECC) was defined as the presence of any dmf
      teeth. Dental plaque was visually inspected on the labial surfaces of upper
      central incisors. Data analysis included Chi-square test, t -test, anova and
      logistic regression modelling. The prevalence of ECC ranged from 3 to 33%
      depending on age group, with a mean dt of 1.1 for 26- to 36-month-olds. No gender
      differences existed in ECC prevalence and mean dt. Dental plaque was visible on
      at least one index tooth for 65-75% of the children. Presence of ECC was related
      to the presence of dental plaque (OR = 1.5; 95% CI 1.0-2.3) when controlling for
      background factors by means of logistic regression. The high occurrence of
      visible plaque and rather high ECC prevalence call for improvement in oral health
      promotion programs of the children.

PMID- 17183181
TI  - Accuracy of electronic apex locator in length determination in the presence of
      different irrigants: An in vitro study.
AB  - Determining the root canal length accurately had been a challenge in endodontics.
      Introduction of apex locators have definitely served as an effective adjuvant to
      radiographs. This in vitro study had attempted to compare the effectiveness of
      electronic apex locator in the presence of various canal contents. Comparison of
      the length determined by apex locators with the radiographic length was also
      made. The results of the study had shown that the length of root canals can be
      accurately made irrespective of the canal contents.

PMID- 17183182
TI  - In vitro comparison of NiTi rotary instruments and stainless steel hand
      instruments in root canal preparations of primary and permanent molar.
AB  - This study is an attempt to compare the NiTi rotary and K-files hand
      instrumentation on root canal preparation of primary and permanent molars for
      their efficiency in preparation time, instrument failure and shaping the canals.
      About 20 primary mandibular second molar (I) and 20 permanent mandibular first
      molar (II) were selected. Each was further divided into 10 for K-files (a) and 10
      for NiTi (b) groups, respectively. Results showed that preparation time Ib Ia and
      IIab<IIa, which was highly significant. In instrument failure, Ia (40%), IIa
      (30%) showed more deformation but not fracture and Ib (10%), IIb (20%) showed
      fracture, but not deformation. Profiles showed good canal taper and smoothness
      compared to the K-files. To conclude profile 0.04 taper 29 series, prepared canal
      rapidly than conventional K-file with good taper, smoothness though the flow was
      not satisfactory. Instrument failure with K-files was less. In primary teeth
      preparation time, instrument failure with profile was less compared to the
      permanent. To conclude it's encouraging to use the profiles in primary teeth.

PMID- 17183183
TI  - Mesiodistal crown dimensions of the permanent dentition in North Indian children.
AB  - This investigation was conducted on 110 individuals, (40 males and 70 females) in
      the age range of 12-18 years. The results revealed the mesiodistal crown
      dimensions of teeth of males to be more than that of the females. Further the
      ratio of the mesiodistal crown dimension of the maxillary lateral incisors to the
      maxillary central incisors was 80% in females and 78% in males. The total arch
      length in males was 117.77 mm in maxilla and 111.60 mm in mandible, while in
      females, the figures were 113.98 mm in maxilla and 107.10 mm in the mandible.

PMID- 17183184
TI  - A multi-disciplinary approach in the management of a traumatized tooth with
      complicated crown-root fracture: A case report.
AB  - A 13-year-old boy had fractured his maxillary right central incisor. The fracture
      line involved 2/3rd of the crown, compromising the pulp and extended
      subgingivally on the palatal aspect invading the biologic width. The procedure
      used to manage this case included endodontic treatment of residual tooth
      orthodontic extrusion to move the fracture line above the alveolar bone. Finally
      the tooth was restored prosthodontically.

PMID- 17183185
TI  - Pyogenic granuloma associated with bone loss in an eight year old child: A case
      report.
AB  - Soft tissue enlargements of the oral cavity often present a diagnostic challenge
      because a diverse group of pathologic processes can produce such lesions. An
      enlargement may represent a variation of normal anatomic structures,
      inflammation, cysts, developmental anomalies and neoplasm. Within these lesions
      is a group of reactive hyperplasias, which develop in response to a chronic,
      recurring tissue injury that stimulates an exuberant or excessive tissue repair
      response. The pyogenic granuloma is a reactive enlargement that is an
      inflammatory response to local irritation such as calculus, a fractured tooth,
      rough dental restoration and foreign materials. This article aims to present a
      case of pyogenic granuloma in 8 year old child patient associated with resorption
      of bone in relation to the tooth.

PMID- 17183186
TI  - Double-rooted primary canines: A report of three cases.
AB  - This article reports three rare cases of birooted primary canines. In one of the
      three cases reported, the double-rooted primary canine was unilateral, which is a
      unique condition in the dental literature. One of the birooted primary canines
      was extracted for examination. Root canal morphology was examined using the
      clearing technique and three root canals were detected. The detection of birooted
      teeth requires a fastidious radiographic evaluation. Moreover, it should be kept
      in mind during endodontic therapy that the number of root canals might exceed the
      number of roots for these teeth.

PMID- 17183187
TI  - In vitro pharmacological characterization of mitemcinal (GM-611), the first acid
      resistant non-peptide motilin receptor agonist, in smooth muscle of rabbit small
      intestine.
AB  - The pharmacological properties of mitemcinal (GM-611), the first acid-resistant
      non-peptide motilin agonist, were investigated in the smooth muscle of the rabbit
      small intestine and compared with porcine motilin (pMTL), erythromycin A (EMA)
      and its derivatives (EM-523, EM-574 and ABT-229). Mitemcinal, pMTL, EMA, EM-523,
      EM-574 and ABT-229 produced concentration-dependent contractions with
      approximately the same maximum contractions in the isolated rabbit duodenum
      longitudinal strips. The contractile response to mitemcinal or pMTL was
      competitively inhibited by a selective motilin antagonist, GM-109. The pA(2)
      values for GM-109 as an antagonist of mitemcinal and pMTL showed approximately
      the same values. However, the concentration-dependent contractile responses to
      mitemcinal or pMTL were not affected by pretreatment with atropine, tetrodotoxin,
      hexamethonium, naloxone or tropisetron. The removal of calcium ions from the
      medium and pretreatment with verapamil greatly suppressed the contractions
      induced by mitemcinal and pMTL. The contractile response to mitemcinal was not
      affected by preincubation in acidic solutions, while those of EM-523, EM-574 and
      ABT-229 were strongly diminished in the same condition. Mitemcinal as well as
      other motilin agonists displaced (125)I-pMTL bound to a homogenate of the rabbit
      duodenum muscle tissue. The displacement curves of all these compounds were
      parallel. These results indicate that mitemcinal is a selective and full motilin
      receptor agonist in the smooth muscle of the rabbit small intestine and that this
      agent has an excellent acid-resistant property.

PMID- 17183188
TI  - Renal protective role of atrial natriuretic peptide in acute sodium overload
      induced inflammatory response.
AB  - BACKGROUND: The present study was performed to explore the effect of exogenous
      infusions of atrial natriuretic peptide (ANP) on the early inflammatory response
      during acute sodium overload in normal rats. METHODS: Sprague Dawley rats were
      exposed to acute sodium overload (Na 1.5 M). Nonhypotensive doses of ANP (1 and 5
      microg x kg(-1) x h(-1)) were infused simultaneously with sodium or after sodium
      infusion in order to evaluate prevention or reversion of the inflammatory
      response, respectively. We determined inflammation markers in renal tissue by
      immunohistochemistry. RESULTS: Creatinine clearance was not reduced in any case.
      Sodium tubular reabsorption increased after sodium overload (334.3 +/- 18.7 vs.
      control 209.6 +/- 27.0 mEq x min(-1), p < 0.05) without changes in mean arterial
      pressure. This increase was prevented (228.9 +/- 26.4; p < 0.05) and reversed
      (231.5 +/- 13.9; p < 0.05) by ANP-5 microg x kg(-1) x h(-1). Sodium overload
      increased the expression of: RANTES (38.4.3 +/- 0.8 vs. 2.9 +/- 0.6%, p < 0.001),
      transforming-growth-factor-beta(1) (35.3 +/- 1.0 vs. 5.0 +/- 0.7%, p < 0.001),
      alpha-smooth muscle actin (15.6 +/- 0.7 vs. 3.1 +/- 0.3%, p < 0.001), NF-kappaB
      (9.4 +/- 1.3 to 2.2 +/- 0.5 cells/mm(2), p < 0.001), HIF-1alpha (38.2 +/- 1.7 to
      8.4 +/- 0.8 cells/mm(2), p < 0.001) and angiotensin II (35.9 +/- 1.3 to 8.2 +/-
      0.5%, p < 0.001). ANP-5 microg x kg(-1) x h(-1) prevented and reversed
      inflammation: RANTES (9.2 +/- 0.5 and 6.9 +/- 0.7, p < 0.001); transforming
      growth factor-beta(1) (13.2 +/- 0.7 and 10.2 +/- 0.5, p < 0.001) and alpha-smooth
      muscle actin (4.1 +/- 0.4 and 5.2 +/- 0.4, p < 0.001). Both prevention and
      reversion by ANP were associated with downregulation of NF-kappaB (3.2 +/- 0.4
      and 2.8 +/- 0.5, p < 0.001) and angiotensin II (8.2 +/- 0.5 and 9.1 +/- 0.7, p <
      0.001) and diminished hypoxia evaluated through HIF-1alpha expression (8.4 +/-
      0.8 and 8.8 +/- 0.7, p < 0.001). CONCLUSION: Our study provides evidence
      supporting a protective role of ANP in both prevention and reversion of renal
      inflammation in rats with acute sodium overload.

PMID- 17183189
TI  - Peroxisome proliferator-activated receptor-gamma is expressed by rat peritoneal
      mesothelial cells: its potential role in peritoneal cavity local defense.
AB  - BACKGROUND/AIMS: Peritoneal mesothelial cells (PMCs) play an important role in
      peritoneal inflammatory and immune response. It was reported that the peroxisomal
      proliferator-activated receptor-gamma (PPARgamma) ligand could effectively reduce
      inflammatory processes. However, the expression and function of PPARgamma in PMCs
      has not been reported. This study was to investigate the expression of PPARgamma
      in rat PMCs and the effect of PPARgamma activation on the production of CD40 and
      ICAM-1 induced by lipopolysaccharide (LPS). METHODS: Rat PMCs (RPMCs) were
      harvested from the peritoneal cavity of Sprague-Dawley rats and maintained under
      defined in vitro conditions. The cells were treated separately with LPS, 15d
      PGJ(2), and ciglitazone at different time points. The mRNA and protein expression
      of PPARgamma, CD40 and ICAM-1 were detected by RT-PCR and Western blot,
      respectively. The intracellular distribution of PPARgamma was detected by
      immunocytochemistry. RESULTS: RPMCs expressed PPARgamma both at the mRNA and
      protein level. The specific signals for PPARgamma were mainly localized in the
      nucleus with weak staining in the cytoplasm. Stimulation of RPMCs with LPS
      resulted in a time-dependent increase in the expression of PPARgamma with the
      peak of mRNA at 3 h and protein at 12 h. Thereafter the expression of PPARgamma
      gradually attenuated. The mRNA expressions for CD40, ICAM-1 and protein
      expression of ICAM-1 were significantly upregulated following stimulation with
      LPS. Both 15d-PGJ(2) and ciglitazone decreased the expression of CD40 mRNA and
      ICAM-1 protein. However, ciglitazone was less effective than 15d-PGJ(2).
      CONCLUSIONS: There is constitutive expression of PPARgamma in cultured RPMCs and
      PPARgamma ligands which strongly inhibit LPS-induced CD40 and ICAM-1 production
      in RPMCs. It suggested that PPARgamma might play a part in the local defense of
      the peritoneal cavity by downregulating inflammatory mediators, which may play a
      potential role in preventing peritoneal fibrosis induced by peritonitis. Further
      in vivo study is needed to demonstrate the long-term effects.

PMID- 17183190
TI  - Creatinine clearance but not serum creatinine alone predicts long-term
      postoperative survival after lower extremity revascularization.
AB  - BACKGROUND: Renal insufficiency is a well-described risk factor for perioperative
      morbidity and shortened survival after major vascular procedures. Due to the
      potential inaccuracy of serum creatinine levels alone in measuring kidney
      function, our aim was to determine whether estimated creatinine clearance more
      consistently predicted long-term survival. METHODS: A retrospective review of one
      institution's vascular registry was performed. Logistic regression analysis was
      conducted to determine independent predictors of 1-, 2- and 3-year postoperative
      mortality. Creatinine clearance was estimated as [140 - age (years)] x weight
      (kg)/72 x serum creatinine (mg/dl), multiplied by 0.85 for women. RESULTS: A
      total of 252 consecutive patients underwent infrainguinal bypass procedures
      between August 1999 and May 2000. Demographics included average age 68 years, 65%
      male, 74% diabetic, 12% dialysis-dependent, 23% history of congestive heart
      failure, 12% history of stroke and 20% serum creatinine >2 mg/dl. One-year
      mortality was 16% (n = 40), 2-year mortality was 25% (n = 64), and 3-year
      mortality was 35% (n = 88). There was no difference in serum creatinine values
      between survivors and non-survivors at 1 year (1.8 vs. 1.9, p = 0.80), 2 years
      (1.8 vs. 2.0, p = 0.62) or 3 years (1.8 vs. 2.0, p = 0.24), and creatinine >2
      mg/dl did not predict long-term adverse outcomes. In contrast, reduced creatinine
      clearance (< or =60 ml/min) was an independent predictor of mortality regardless
      of dialysis status (1 year: OR = 2.53, p = 0.014; 2 years: OR = 2.46, p = 0.004;
      3 years: OR = 2.45, p = 0.001), and creatinine clearance was higher for survivors
      versus non-survivors at all 3 time points (1 year: 70.2 vs. 49.5, p = 0.003; 2
      years: 72.3 vs. 51.2, p < 0.0001; 3 years: 74.7 vs. 52.6, p < 0.0001). Other
      independent predictors of mortality included a history of stroke (1 year: OR =
      3.28, p = 0.008; 2 years: OR = 2.55, p = 0.025; 3 years: OR = 2.35, p = 0.038)
      and congestive heart failure (1 year: OR = 2.86, p = 0.006; 2 years: OR = 2.54, p
      = 0.005; 3 years: OR = 2.13, p = 0.017). CONCLUSIONS: Independent of dialysis
      status, a decreased creatinine clearance, but not elevated serum creatinine
      alone, is an independent predictor of mortality after lower extremity arterial
      reconstruction. Determination of creatinine clearance should replace serum
      creatinine in the preoperative risk evaluations of patients undergoing major
      vascular surgical procedures.

PMID- 17183191
TI  - Quality and quantity of life with pancreatic cancer.

PMID- 17183192
TI  - Glucocorticoids down-regulate lipopolysaccharide-induced de novo production of
      neurotensin mRNA in the rat hypothalamic, paraventricular, corticotrophin
      releasing hormone neurons.
AB  - OBJECTIVE: Intraperitoneal injection of the endotoxin lipopolysaccharide (LPS)
      produces inflammation accompanied by activation of the immune system and the
      secretion of cytokines. Cytokines stimulate the hypothalamo-pituitary-adrenal
      (HPA) axis to release the anti-inflammatory corticosterone which controls its own
      production by acting on the HPA axis. Upstream in the HPA axis are neuroendocrine
      corticotrophin-releasing hormone (CRH) neurons located in the paraventricular
      nucleus (PVN), whose multipeptidergic phenotype changes during inflammation:
      while CRH mRNA is up-regulated in these conditions, neurotensin (NT) mRNA
      expression is induced de novo. The negative feedback control of glucocorticoids
      on CRH production is well documented; however, their action on NT production in
      the PVN of the hypothalamus is poorly documented. The aim of this study was to
      determine if glucocorticoids modulate the de novo production of NT during
      inflammation. METHODS: Using quantitative in situ hybridization histochemistry,
      we examined whether the absence (adrenalectomy) or excess (corticosterone
      implants) of glucocorticoids modulate de novo production of NT mRNA in the PVN
      during inflammation induced by LPS treatment. RESULTS: A relatively low dose of
      LPS (50 microg/kg) that is not efficient to induce NT mRNA production in the PVN
      becomes efficient after adrenalectomy. Moreover, corticosterone excess reduces
      LPS-induced production of NT mRNA in the PVN. CONCLUSION: Glucocorticoids exert a
      negative control on NT mRNA production in the PVN of the hypothalamus, and this
      effect requires that NT mRNA production be triggered, such as during
      inflammation.

PMID- 17183193
TI  - Intraocular fluid-air exchange reduces retinal ganglion cell activity.
AB  - AIM: To demonstrate the influence of intraocular fluid-air exchange on retinal
      ganglion cell activity. METHODS: In two cats lensectomy and vitrectomy were
      performed in a two-step approach 2 weeks prior to recording experiments. To
      measure retinal activity, up to two fiber microelectrodes were inserted via a
      scleral port. Precise micromanipulator positioning of the electrodes' tips onto
      the inner retinal surface were verified by ophthalmoscopy and simultaneous
      electrical recording. Neuronal activity of the retina was continuously recorded
      with or without visual stimulation. We maintained the intraocular pressure
      constant at 29 mm Hg. Fluid-air exchange and fluid refill were performed with an
      infusion tube integrated in the manipulator and slowly to avoid direct
      mechanical/stream-based damage of the retina. RESULTS: We found that fluid-air
      exchange leads to a rapid reduction of spontaneous as well as visually evoked
      retinal ganglion cell activity. The activity started to diminish within few
      minutes, and then it halved approximately every 3 min. Even 1 h after eye fluid
      refill, the retinal activity recovered only partially. CONCLUSION: Decrease in
      retinal activity after fluid-air exchange can be explained by mechanical stress
      induced drying of the inner retinal surface and by potential changes of
      extracellular ion concentration. Since even moderate airstream-based fluid-air
      exchanges can lead to retinal damage, the surgeon should minimize the quantity of
      air passing open sclerotomy sites until a better understanding of the retinal
      effects of this essential technique in modern vitrectomy is available.

PMID- 17183194
TI  - Helicobacter pylori: an underestimated factor in acute anterior uveitis and
      spondyloarthropathies?
AB  - Acute anterior uveitis (AAU) is the most common form of intraocular inflammation,
      but its aetiology is still unclear. Fifty percent of AAU patients are HLA-B27
      positive, and half of these also have spondyloarthropathies (SpA). Numerous
      serological studies have shown elevated levels of serum antibodies to various
      Gram-negative bacteria in HLA-B27-positive AAU and SpA patients. Antigenic
      similarities between these bacteria and host components (HLA-B27) have already
      been shown. Still, the mechanism underlying these diseases has not been
      clarified. Among the Gram-negative bacteria, Helicobacter pylori has not been
      screened in AAU patients. The purpose of our study was to see if this common
      human pathogen somehow interferes with AAU. In addition Chlamydia trachomatis,
      Yersinia enterocolitica 03 and 09, Salmonella sp. and Proteus OX19 were also
      examined. A total of 60 patients consisting of 4 groups (15 patients with AAU, 15
      with SpA, 15 with AAU+SpA and 15 healthy control persons) were examined. A high
      percentage of the serological results of all investigated bacteria was positive:
      80% in the AAU, 93.3% in the SpA and 100% in the AAU+SpA group, while it amounted
      to 66.7% in the control group (p < 0.05). H. pylori showed the highest percentage
      of positivity in all 3 patient groups (66.7% in the AAU, 73.3% in the SpA and 80%
      in the AAU+SpA group). In contrast, 26.7% of the controls were anti-H.-pylori
      positive, thus showing a statistically significant difference between the
      patients and the control group (p < 0.05). HLA-B27/B7-CREG positivity was
      detected in 53.3% of the AAU, 66.7% of the SpA and 93.3% of the AAU+SpA patients
      and in none of the controls. Our results suggest that H. pylori might be a
      candidate participating in the development of AAU and SpA. They also support the
      theory of genetic (HLA-B27) and exogenous factors (Gram-negative bacteria) as
      probable background of these diseases.

PMID- 17183195
TI  - Topical mitomycin C for the treatment of conjunctival tumor.
AB  - BACKGROUND: To evaluate the efficacy of topical mitomycin C (MMC) for the
      treatment of conjunctival tumor in a prospective design. METHODS: Nine patients
      (nine eyes) with conjunctival tumor were studied. The patients received topical
      MMC 0.04% four times daily by one to six courses. Each course consisted of
      medication for consecutive 7 days followed by 1 week without medication. Follow
      up was conducted on patients for control of disease, and side effects. RESULTS:
      In 7 patients, the tumor completely disappeared during the mean follow-up period
      of 24.57 +/- 5.94 months (range 18-35 months) with no recurrence. In 1 patient,
      there was no regression of the tumor, and in 1 patient cessation of the treatment
      was needed because of an adverse effect of the drug. CONCLUSION: Topical MMC is
      effective for the treatment of conjunctival tumor. Longer follow-up and large
      series are needed to assess the duration of tumor control.

PMID- 17183196
TI  - Visual outcomes and associated risk factors of cataract surgeries in highly
      myopic Taiwanese.
AB  - AIMS: The purposes of this study are to describe the visual outcome of highly
      myopic eyes undergoing cataract surgery, to investigate associated risk factors
      for poor postoperative vision and to assess the postoperative complication
      frequency among the myopic Taiwanese population. METHODS: We conducted a
      retrospective, noncomparative case series study at the Department of
      Ophthalmology, Zhongxing Branch, Taipei City Hospital, Taiwan. High myopia was
      defined as axial length > or =26.0 mm. The main study outcomes were visual acuity
      for the initial 6-month postoperative period (including visual acuities and
      improvement of postoperative vision) and postoperative complications (including
      subsequent cataract formation and postoperative retinal detachment). RESULTS:
      Fifty-two highly myopic eyes were enrolled between January 2002 and December
      2004. The mean follow-up interval was 43.3 +/- 20.2 weeks (range 25-103). Thirty
      two eyes (61.5%) had good postoperative visual improvement (> or =4 lines of
      Snellen chart). Thirty-seven eyes (71.2%) achieved good postoperative vision
      (20/40 or better). Fifteen eyes (28.8%) demonstrated poor postoperative vision.
      Pre-existing maculopathy was an independent risk factor for failure to achieve
      good postoperative vision [odds ratio (OR): 6.84, 95% confidence interval (CI):
      1.12-41.8] and improvement (OR: 16.1, 95% CI: 2.2-119.9). Diabetic history was
      considered another independent risk factor for poor postoperative vision (OR:
      15.6, 95% CI: 0.97-267.6). Six eyes (11.5%) developed subsequent posterior
      capsular opacification requiring Nd:YAG laser capsulotomy. Two eyes (3.8%)
      developed retinal detachment during follow-up. CONCLUSIONS: Most highly myopic
      eyes achieved good visual improvement and good postoperative visual acuity after
      cataract surgery. Pre-existing maculopathy was an independent risk factor of
      postoperative visual improvement and status. It is crucial to examine retinal
      status prior to cataract surgery to prevent poor vision improvement, poor
      postoperative vision or retinal complications.

PMID- 17183197
TI  - Safety and efficacy of micro-incisional cataract surgery with bimanual
      phacoemulsification for white mature cataract.
AB  - BACKGROUND: To evaluate the safety and efficacy of micro-incisional cataract
      surgery (MICS) with bimanual phacoemulsification for the management of white
      mature cataract. METHODS: Twenty-five eyes in 25 patients with mature cataract
      were prospectively recruited to undergo MICS with bimanual phacoemulsification.
      Serial changes in best-corrected visual acuity (BCVA), central corneal thickness
      (CCT) and endothelial cell density (ECD) were compared using the Wilcoxon signed
      rank test. RESULTS: MICS was successfully performed in 24 (96%) of the 25 eyes,
      with 1 eye requiring conversion to extracapsular cataract extraction due to
      radial tear during continuous curvilinear capsulorhexis. The median preoperative
      BCVA was hand movement. On day 1 postoperatively, the median BCVA improved to 0.6
      (p < 0.001 compared with baseline). All patients had BCVA of 0.6 or better at 3
      months after surgery (p < 0.001 compared with baseline). The mean increase in CCT
      at day 1 and week 1 postoperatively was 11.5 and 7.1%, respectively. The change
      in mean CCT was no longer significant at month 3 postoperatively (p = 0.82). The
      mean reduction in ECD at 3 months postoperatively was 7.8% (p = 0.037). None of
      the patients developed any postoperative complications. CONCLUSIONS: MICS with
      bimanual phacoemulsification appeared to be a promising alterative for the
      management of white mature cataract.

PMID- 17183198
TI  - Effect of ultraviolet B radiation on the absorption characteristics of various
      intraocular lenses.
AB  - BACKGROUND: The aim of this study was to determine the effect of ultraviolet B
      (UVB) exposure on UV filters of various intraocular lenses (IOLs). METHODS: Eight
      samples each of the hydrophobic acrylic, hydrophilic acrylic and silicone IOLs
      were used. Four IOLs of each type was selected randomly as the control group
      while the remaining four IOLs of each type were exposed to a UVB dose of 1.4
      J/cm(2) (2.40 mW/cm(2)) for 9.45 min, two times with a 4-week interval. IOLs were
      evaluated for any sign of opacification under microscope weekly. After a follow
      up period of 16 weeks, spectrometry for UV filter absorption rates, scanning
      electron microscopy for deposit formation and energy dispersive X-ray analysis
      for elemental composition were performed for all IOLs, and findings of the
      control group IOLs were compared with those of the UVB-exposed IOLs. All these
      procedures were done at the Department of Ophthalmology, Faculty of Medicine,
      Dokuz Eylul University. RESULTS: All the IOLs were free of any opacification
      during the follow-up period. Spectrometric analysis of their UV filters revealed
      a change in absorption rates in the hydrophilic acrylic and silicone IOLs
      compared to the control IOLs of the same type. Only the hydrophobic acrylic IOLs
      preserved the same UV absorption curve after UVB exposure. CONCLUSION: The
      pathogenesis of IOL opacification is still undetermined. Some reports claimed
      that the UV light was the responsible factor. Our experimental study revealed
      that high doses of UVB did not cause any opacification though they impaired the
      function of UV filters of the hydrophilic acrylic and silicone IOLs.

PMID- 17183199
TI  - Clinical study of endoscopic endonasal conjunctivodacryocystorhinostomy with
      Jones tube placement.
AB  - PURPOSE: To evaluate the efficacy of endoscopic endonasal primary
      conjunctivodacryocystorhinostomy (CDCR) and revision CDCR after primary CDCR.
      METHODS: Twenty-four patients who had undergone endoscopic endonasal CDCR with a
      Jones tube and who were followed up for over 6 months at our hospital were
      reviewed retrospectively. Our analysis included success rate, operation times,
      and causes of failure. RESULTS: The indications for revision CDCR were Jones tube
      prolapse and inadequate tube length. The initial success rate in the primary and
      revision groups were 78.6% (11/14) and 100% (10/10), respectively, and their mean
      operation times were 24 min (+/- 6.3) and 21 min (+/- 6.1), respectively. Main
      causes of failure included inaccurate tube length and abnormal tube position.
      CONCLUSIONS: Endoscopic endonasal CDCR appears to be a reasonable revision and
      primary approach, because it allows Jones tube length to be measured accurately
      during surgery, and an 18- to 20-mm Jones tube length was used in most cases.

PMID- 17183201
TI  - Changes in colour discrimination during the menstrual cycle.
AB  - A group of normal women of reproductive age were recruited to investigate colour
      discrimination during the various phases of the menstrual cycle. Colour vision
      was tested with the Farnsworth-Munsell 100-hue arrangement test, and the test was
      administered at 3 time points: the beginning of the cycle, ovulation, and the end
      of the cycle. We found that colour discrimination was better at ovulation than at
      the other 2 time points. It is possible that psychological as well as hormonal
      factors could contribute to improved colour vision performance at ovulation.

PMID- 17183200
TI  - Antiphospholipid antibodies in ocular arterial and venous occlusive disease.
AB  - PURPOSE: It was the aim of this study to evaluate antiphospholipid antibodies
      (APA), i.e. lupus anticoagulants (LA) and anticardiolipin (ACA) IgG and IgM, in
      ophthalmic occlusive disease. METHODS: Over a 3.5-year period, APA were evaluated
      in 368 patients. RESULTS: Eighty-six patients (23.4%), compared to 5% in the
      general population, tested positive for APA. APA did not differ significantly
      between patients with venous (20.6%) or arterial (25.5%) occlusive disease. This
      included 93 patients with central retinal vein occlusion (18% APA positive), 67
      with retinal branch vein occlusion (24% APA positive), 41 with central retinal
      artery occlusion (22% APA positive), 53 with retinal branch artery occlusion (32%
      APA positive), 71 with anterior ischemic optic neuropathy (23% APA positive), 12
      with posterior ischemic optic neuropathy (33% APA positive) and 31 patients with
      amaurosis fugax (23% APA positive). Excluding patients with accepted main risk
      factors, APA were positive in 15.3% of 85 patients. CONCLUSION: The high APA
      prevalence confirms its relevance in ocular occlusive disorders.

PMID- 17183202
TI  - Collagen shields as a drug delivery system for the fourth-generation
      fluoroquinolones.
AB  - PURPOSE: To evaluate the penetration of commercially available gatifloxacin and
      moxifloxacin into the anterior chamber of a rabbit eye using collagen shields
      presoaked in the antibiotics as a drug delivery system. METHODS: Collagen
      shields, presoaked for 10 min in commercially available solutions of gatifloxacin
      (diluted intravenous Tequin) or moxifloxacin (Vigamox) with the same
      concentration, were placed on the surface of each of the corneas of 12 rabbits
      for a total of 24 eyes (12 in each group). Aqueous humor samples were taken 3 and
      6 h later. RESULTS: The concentrations of both antibiotics were high after 3 h
      (3.1 +/- 1.3 microg/ml for moxifloxacin and 2.3 +/- 0.8 microg/ml for
      gatifloxacin, p = 0.22). The concentration of gatifloxacin after 6 h was
      statistically significantly higher than for moxifloxacin (0.76 +/- 0.33 microg/ml
      vs. 0.29 + 0.14 microg/ml, respectively, p = 0.03). CONCLUSION: Our results
      suggest that collagen shields can be effective as a drug delivery system for the
      fourth-generation fluoroquinolones with a longer effect for gatifloxacin.

PMID- 17183203
TI  - Pneumatic displacement of submacular hemorrhage due to age-related macular
      degeneration.
AB  - PURPOSE: Subretinal hemorrhage is one of the most serious complications of
      exudative age-related macular degeneration (AMD). Treatment with vitreous surgery
      with or without plasminogen activator, fluid-gas exchange, or perfluorocarbon
      yields only a small improvement in visual acuity. PATIENTS AND METHODS: The files
      of 24 patients with submacular hemorrhage secondary to AMD who were treated by
      injection of perfluoropropane gas (C(3)F(8)) (11 patients) or sulfur hexafluoride
      (SF(6)) (13 patients) were reviewed for visual acuity before and after the
      procedure and time of treatment from onset of symptoms. RESULTS: For the whole
      sample, pneumatic displacement led to a statistically significant improvement in
      mean visual acuity (p = 0.015). A significant difference between pre- and
      postoperative visual acuity was found for the patients treated with SF(6) (p =
      0.034), but not for the patients treated with C(3)F(8) (p = 0.245). CONCLUSION:
      The use of gas injection to displace submacular hemorrhage can significantly
      improve visual acuity.

PMID- 17183204
TI  - Case reports of three patients showing optic nerve head melanocytoma and systemic
      hypertension.
AB  - PURPOSE: To report the association of optic disk melanocytoma with systemic
      hypertension. CASES: Ocular examination of 3 asymptomatic hypertensive patients
      revealed a pigmented lesion over the optic disk. After clinical examination and
      radiological evaluation a diagnosis of optic disk melanocytoma was made. One
      patient had a mild decrease in visual acuity associated with an increase in size
      of the lesion during the follow-up. Systemic evaluation revealed increased
      urinary vanillylmandelic acid in all the patients. MRI showed diffuse adrenal
      hyperplasia while a (131)I-MIBG scan showed increased uptake in 1 case.
      CONCLUSIONS: Optic disk melanocytoma is a benign tumor though the lesion may
      increase in size with the resultant decrease in visual acuity over few years. It
      may be associated with systemic hypertension secondary to increased levels of
      catecholamines in the body, which is related to the common neural crest origin of
      melanocytes, adrenal medullary cells and chromaffin cells.

PMID- 17183205
TI  - Topical anesthesia in transconjunctival sutureless 25-gauge vitrectomy for
      macular-based disorders.
AB  - PURPOSE: To evaluate the safety and feasibility of topical anesthesia in
      vitrectomy using the transconjunctival sutureless 25-gauge system (TSV 25G).
      METHODS: TSV 25G vitrectomy was performed prospectively in 46 eyes of 46 patients
      with macular-based disorders, including macular holes (n = 31), idiopathic
      epiretinal membranes (n = 11), and vitreoretinal traction syndrome (n = 4).
      Topical anesthesia was administered in each patient by instilling 2% Alcaine at 5
      min intervals, three times before surgery. Additional Alcaine drops were given as
      a supplementation if needed during the operation. The levels of intraoperative
      analgesia were graded from 1 (adequate) to 3 (inadequate). RESULTS: Thirty-one
      patients (67.4%) tolerated the procedure well, with no additional anesthetic
      agent. Thirteen patients (28.3%) required additional topical anesthesia and 2
      patients (4.3%) required a systemic sedative. Intraoperative pain occurred when
      the sclera was pierced by the microcannula and when sclera indentation was
      performed. No patient required additional retrobulbar or peribulbar anesthesia.
      There was no intraoperative complication which was specifically related to
      topical anesthesia. CONCLUSION: Topical anesthesia permits the successful
      management of some surgically less complex vitreoretinal disorders when the TSV
      25G is used.

PMID- 17183206
TI  - Carbon and nitrogen regulation in gram-positive bacteria: a tribute to Milton H.
      Saier, Jr.

PMID- 17183207
TI  - Sugar transport systems of Bifidobacterium longum NCC2705.
AB  - Here we present the complement of the carbohydrate uptake systems of the strictly
      anaerobic probiotic Bifidobacterium longum NCC2705. The genome analysis of this
      bacterium predicts that it has 19 permeases for the uptake of diverse
      carbohydrates. The majority belongs to the ATP-binding cassette transporter
      family with 13 systems identified. Among them are permeases for lactose, maltose,
      raffinose, and fructooligosaccharides, a commonly used prebiotic additive. We
      found genes that encode a complete phosphotransferase system (PTS) and genes for
      three permeases of the major facilitator superfamily. These systems could serve
      for the import of glucose, galactose, lactose, and sucrose. Growth analysis of
      NCC2705 cells combined with biochemical characterization and microarray data
      showed that the predicted substrates are consumed and that the corresponding
      transport and catabolic genes are expressed. Biochemical analysis of the PTS, in
      which proteins are central in regulation of carbon metabolism in many bacteria,
      revealed that B. longum has a glucose-specific PTS, while two other species
      (Bifidobacterium lactis and Bifidobacterium bifidum) have a fructose-6-phosphate
      forming fructose-PTS instead. It became obvious that most carbohydrate systems
      are closely related to those from other actinomycetes, with a few exceptions. We
      hope that this report on B. longum carbohydrate transporter systems will serve as
      a guide for further in-depth analyses on the nutritional lifestyle of this
      beneficial bacterium.

PMID- 17183208
TI  - The phosphotransferase system of Lactobacillus casei: regulation of carbon
      metabolism and connection to cold shock response.
AB  - Genome sequencing of two different Lactobacillus casei strains (ATCC334 and BL23)
      is presently going on and preliminary data revealed that this lactic acid
      bacterium possesses numerous carbohydrate transport systems probably reflecting
      its capacity to proliferate under varying environmental conditions. Many
      carbohydrate transporters belong to the phosphoenolpyruvate:sugar
      phosphotransferase system (PTS), but all different kinds of non-PTS transporters
      are present as well and their substrates are known in a few cases. In L. casei
      regulation of carbohydrate transport and carbon metabolism is mainly achieved by
      PTS proteins. Carbon catabolite repression (CCR) is mediated via several
      mechanisms, including the major P-Ser-HPr/catabolite control protein A (CcpA)
      dependent mechanism. Catabolite response elements, the target sites for the P-Ser
      HPr/CcpA complex, precede numerous genes and operons. PTS regulation domain
      containing antiterminators and transcription activators are also present in both
      L. casei strains. Their activity is usually controlled by two PTS-mediated
      phosphorylation reactions exerting antagonistic effects on the transcription
      regulators: P~EIIB-dependent phosphorylation regulates induction of the
      corresponding genes and P~His-HPr-mediated phosphorylation plays a role in CCR.
      Carbohydrate transport of L. casei is also regulated via inducer exclusion and
      inducer expulsion. The presence of glucose, fructose, etc. leads to inhibition of
      the transport or metabolism of less favorable carbon sources (inducer exclusion)
      or to the export of accumulated non-metabolizable carbon sources (inducer
      expulsion). While P-Ser-HPr is essential for inducer exclusion of maltose, it is
      not necessary for the expulsion of accumulated thio-methyl-beta-D
      galactopyranoside. Surprisingly, recent evidence suggests that the PTS of L.
      casei also plays a role in cold shock response.

PMID- 17183209
TI  - Genomic analysis of the phosphotransferase system in Clostridium botulinum.
AB  - Clostridium botulinum is capable of fermenting carbohydrates, but there have been
      no detailed studies of the uptake of sugars and related substrates. In bacteria,
      a common and often predominant system of carbohydrate uptake is the
      phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS). This multi
      protein complex catalyses a group translocation involving both uptake and
      phosphorylation of carbohydrates, and is also known to play an important role in
      environmental sensing and metabolic regulation. The genome of C. botulinum
      encodes 15 PTSs which have a similar domain structure to the PTS in other
      bacteria. Based on phylogenetic relationships and analysis of gene clusters, the
      C. botulinum PTS appears to be involved in the uptake of hexoses, hexose
      derivatives and disaccharides. C. botulinum also contains the components of PTS
      associated regulatory mechanisms which have been characterised in other bacteria.
      It therefore seems likely that the PTS plays a significant, and previously
      unrecognised, role in the physiology of this bacterium.

PMID- 17183210
TI  - The phosphotransferase system of Corynebacterium glutamicum: features of sugar
      transport and carbon regulation.
AB  - In this review, we describe the phosphotransferase system (PTS) of
      Corynebacterium glutamicum and discuss genes for putative global carbon
      regulation associated with the PTS. C. glutamicum ATCC 13032 has PTS genes
      encoding the general phosphotransferases enzyme I, HPr and four enzyme II
      permeases, specific for glucose, fructose, sucrose and one yet unknown substrate.
      C. gluamicum has a peculiar sugar transport system involving fructose efflux
      after hydrolyzing sucrose transported via sucrose EII. Also, in addition to their
      primary PTS, fructose and glucose are each transported by a second transporter,
      glucose EII and a non-PTS permease, respectively. Interestingly, C. glutamicum
      does not show any preference for glucose, and thus co-metabolizes glucose with
      other sugars or organic acids. Studies on PTS-mediated sugar uptake and its
      related regulation in C. glutamicum are important because the production yield of
      lysine and cell growth are dependent on the PTS sugars used as substrates for
      fermentation. In many bacteria, the PTS is also involved in several regulatory
      processes. However, the detailed molecular mechanism of global carbon regulation
      associated with the PTS in this organism has not yet been revealed.

PMID- 17183211
TI  - RamA, the transcriptional regulator of acetate metabolism in Corynebacterium
      glutamicum, is subject to negative autoregulation.
AB  - The RamA protein represents a LuxR-type transcriptional activator of genes
      involved in acetate metabolism of Corynebacterium glutamicum. Here we analyze the
      expression of the respective ramA gene and its regulation. Transcription was
      found to start 71 nucleotides upstream of the translational start codon and to be
      two- to threefold up-regulated in the presence of acetate in the growth medium.
      Accordingly, about twofold higher amounts of RamA were observed in C. glutamicum
      cells grown on acetate instead of glucose. Using cell extracts of C. glutamicum
      and employing DNA affinity chromatography, we found RamA itself as the main
      protein which binds to the ramA promoter region. By electrophoretic mobility
      shift analysis with the ramA promoter region and His-tagged RamA protein,
      multiple RamA-binding sites were identified in front of the ramA transcriptional
      start site. Transcriptional cat fusion experiments revealed that ramA promoter
      activity was about threefold higher in a RamA-deficient mutant of C. glutamicum
      than in the wild-type, however, acetate-dependent up-regulation of ramA
      expression was not affected in the RamA-negative mutant. These results indicate
      that RamA negatively controls the expression of its own gene, but is not involved
      in acetate-dependent up-regulation of ramA expression.

PMID- 17183212
TI  - Conserved cis-acting elements upstream of genes composing the chitinolytic system
      of streptomycetes are DasR-responsive elements.
AB  - For soil-dwelling bacteria that usually live in a carbon-rich and nitrogen-poor
      environment, the ability to utilize chitin - the second most abundant
      polysaccharide on earth - is a decisive evolving advantage as it is a source for
      both elements. Streptomycetes are high-GC Gram-positive soil bacteria that are
      equipped with a broad arsenal of chitinase-degrading genes. These genes are
      induced when the streptomycetes sense the presence of chitooligosaccharides.
      Their expression is repressed as soon as more readily assimilated carbon sources
      become available. This includes for example glucose or N-acetylglucosamine, the
      monomer subunit of chitin. Historically, the first cis-acting elements involved
      in carbon regulation in streptomycetes were found more than a decade ago upstream
      of chitinase genes, but the transcriptional regulator had so far remained
      undiscovered. In this work, we show that these cis-acting elements consist of
      inverted repeats with multiple occurrences and are bound by the HutC/GntR type
      regulator DasR. We have therefore designated these sites as DasR-responsive
      elements (dre). DasR, which is also the repressor of the genes for the N
      acetylglucosamine-specific phosphotransferase transport system, should therefore
      play a critical role in sensing the balance between the monomeric and polymeric
      forms of N-acetylglucosamine.

PMID- 17183213
TI  - A new piece of an old jigsaw: glucose kinase is activated posttranslationally in
      a glucose transport-dependent manner in streptomyces coelicolor A3(2).
AB  - Members of the soil-dwelling prokaryotic genus Streptomyces are indispensable for
      the recycling of complex polysaccharides, and produce a wide range of natural
      products. Nutrient limitation is likely to be a major signal for the onset of
      their development, resulting in spore formation by specialized aerial hyphae.
      Streptomycetes grow on numerous carbon sources, which they utilize in a
      preferential manner. The main signaling pathway underlying this phenomenon is
      carbon catabolite repression, which in streptomycetes is totally dependent on the
      glycolytic enzyme glucose kinase (Glk). How Glk exerts this fascinating dual role
      (metabolic and regulatory) is still largely a mystery. We show here that while
      Glk is made constitutively throughout the growth of Streptomyces coelicolor
      A3(2), its catalytic activity is modulated in a carbon source-dependent manner:
      while cultures growing exponentially on glucose exhibit high Glk activity,
      mannitol- grown cultures show negligible activity. Glk activity was directly
      proportional to the amount of two Glk isoforms observed by Western blot analysis.
      The activity profile of GlcP, the major glucose permease, correlated very well
      with that of Glk. Our data are consistent with a direct interaction between Glk
      and GlcP, suggesting that a Glk-GlcP permease complex is required for efficient
      glucose transport by metabolic trapping. This is supported by the strongly
      reduced accumulation of glucose in glucose kinase mutants. A model to explain our
      data is presented.

PMID- 17183214
TI  - A glucose kinase from Mycobacterium smegmatis.
AB  - Carbon metabolism and regulation is poorly understood in mycobacteria, a genus
      that includes some major pathogenic species like Mycobacterium tuberculosis and
      Mycobacterium leprae. Here, we report the identification of a glucose kinase from
      Mycobacterium smegmatis. This enzyme serves in glucose metabolism and global
      carbon catabolite repression in the related actinomycete Streptomyces coelicolor.
      The gene, msmeg1356 (glkA), was found by means of in silico screening. It was
      shown that it occurs in the same genetic context in all so far sequenced
      mycobacterial species, where it is located in a putative tricistronic operon
      together with a glycosyl hydrolase and a putative malonyl-CoA transacylase.
      Heterologous expression of glkA in an Escherichia coli glucose kinase mutant led
      to the restoration of glucose growth, which provided in vivo evidence for glucose
      kinase function. GlkA(Msm) was subsequently overproduced in order to study its
      enzymatic features. We found that it can form a dimer and that it efficiently
      phosphorylates glucose at the expense of ATP. The affinity constant for glucose
      was with 9 mM about eight times higher and the velocity was about tenfold slower
      when compared to the parallel measured glucose kinase of S. coelicolor. Both
      enzymes showed similar substrate specificity, which consists in an ATP-dependent
      phosphorylation of glucose and no, or very inefficient, phosphorylation of the
      glucose analogues 2-deoxyglucose and methyl alpha-glucoside. Hence, our data
      provide a basis for studying the role of mycobacterial glucose kinase in vivo to
      unravel possible catalytic and regulatory functions.

PMID- 17183215
TI  - Transcriptome analysis of temporal regulation of carbon metabolism by CcpA in
      Bacillus subtilis reveals additional target genes.
AB  - The pleiotropic regulator of carbon metabolism in Gram-positive bacteria, CcpA,
      regulates gene expression by binding to so-called cre elements, which are located
      either upstream or in promoter regions, or in open-reading frames. In this study
      we compared the transcriptomes of Bacillus subtilis 168 and its ccpA deletion
      mutant during growth in glucose-containing rich medium. Although growth was
      similar, glucose was completely consumed by the wild-type strain in the
      stationary phase, while it was still present in the culture of the mutant. At
      that stage, direct and indirect effects on gene expression were observed. During
      exponential growth, CcpA mainly influences the carbohydrate and energy
      metabolism, whereas from transition phase onwards its function expands on a
      broader range of physiological processes including nucleotide metabolism, cell
      motility and protein synthesis. A genome wide search revealednew putative cre
      sites, which could function in vivo according to our transcriptome data.
      Comparison of our data with published transcriptome data of ccpA mutant analysis
      in the exponential growth phase confirmed earlier identified CcpA regulon
      members. It also allowed identification of potential new CcpA-repressed genes,
      amongst others ycgN and the ydh operon. Novel activated members include opuE
      andthe opuAABC, yhb and man operons, which all have a putative cre site that
      appears to be dependent on helical topology. A comparative analysis of these
      genes with the known activated genes i.e.ackA and pta revealed the presence of a
      possible upstream activating region (UAR) as has been shown to be functional for
      the activation of ackA. The data suggest that at later growth phases CcpA may
      regulate gene expression by itself or complexed with other, yet unknown
      cofactors.

PMID- 17183216
TI  - CcpA mutants with differential activities in Bacillus subtilis.
AB  - CcpA is the master regulator for carbon catabolite regulation in Bacillus
      subtilis and regulates more than 300 genes by repression or activation. To
      revealthe effects of different functional domains of CcpA on various regulatory
      modes, we compared the activities of CcpA point mutants in activation (alsS,
      ackA) and repression (xynP, gntR). CcpA variants mutated at residues in the
      HPrSerP-binding region without allosteric functions are inactive. On the other
      hand, CcpA variants mutated at residues that change their conformation upon
      HPrSerP or CrhP binding regulate only ackA. Another set of mutants with
      alterations in the corepressor-binding region show glucose-independent regulation
      of xynP. The data presented here demonstrate the involvement of HPrSerP and/or
      CrhP in activation of ackA and alsS by CcpA. Furthermore, these data also
      indicate that activation and repression mediated by CcpA may utilize different
      conformational changes of the protein.

PMID- 17183217
TI  - Characterization of Bacillus subtilis mutants with carbon source-independent
      glutamate biosynthesis.
AB  - Bacillus subtilis synthesizes glutamate from 2-oxoglutarate and glutamine using
      the glutamate synthase, encoded by the gltAB operon. Glutamate degradation
      involves the catabolic glutamate dehydrogenase (GDH) RocG. Expression of both
      gltAB and rocG is controlled by the carbon and nitrogen sources. In the absence
      of glucose or other well-metabolizable carbon sources, B. subtilis is unable to
      grow unless provided with external glutamate. In this work, we isolated mutations
      that suppressed this growth defect of B. subtilis on minimal media (sgd mutants).
      All mutations enabled the cells to express the gltAB operon even in the absence
      of glucose. The mutations were all identified in the rocG gene suggesting that
      the catabolic GDH is essential for controlling gltAB expression in response to
      the availability of sugars.

PMID- 17183218
TI  - Carbon catabolite repression of sucrose utilization in Staphylococcus xylosus:
      catabolite control protein CcpA ensures glucose preference and autoregulatory
      limitation of sucrose utilization.
AB  - Sucrose utilization in Staphylococcus xylosus is dependent on two genes, scrA and
      scrB; encoding a PTS permease and a sucrose phosphate hydrolase, respectively.
      The genes are encoded on separate loci and are transcribed from two promoters,
      P(scrA) and P(scrB), both of which are controlled by the repressor ScrR by
      binding to the operator sequences O(A) and O(B). In the scrA promoter region, a
      catabolite-responsive element (cre), operator for the global catabolite control
      protein CcpA, is also present, but its contribution to scrA regulation has not
      been determined. Using an integrative promoter probe plasmid, the activities of
      the promoters P(scrA) and P(scrB) were determined under different growth
      conditions. Both promoters are induced by sucrose and induction is prevented when
      glucose is also present. Without a functional CcpA, glucose-mediated prevention
      of induction is lost, clearly demonstrating that CcpA ensures hierarchical sugar
      utilization with glucose as preferred substrate. Measurements of promoter
      activities in the absence of a functional ScrR repressor indicated that CcpA also
      acts upon the operators O(A) and O(B), albeit not as efficiently as on the
      genuine cre in P(srcA). Besides determining the choice of the carbon source, CcpA
      has a second effect on sucrose gene expression. When sucrose is the sole carbon
      source, sucrose catabolism activates carbon catabolite repression and CcpA
      prevents full induction of the sucrose utilization genes by partially repressing
      the scrA promoter. Thus, CcpA-dependent regulation serves as a built-in
      autoregulatory device to restrict sucrose uptake.

PMID- 17183219
TI  - Global gene expression profiling of Bacillus subtilis in response to ammonium and
      tryptophan starvation as revealed by transcriptome and proteome analysis.
AB  - The global gene expression profile of Bacillus subtilis in response to ammonium
      and tryptophan starvation was analyzed using transcriptomics and proteomics which
      gained novel insights into these starvation responses. The results demonstrate
      that both starvation conditions induce specific, overlapping and general
      starvation responses. The TnrA regulon, the glutamine synthetase (glnA) as well
      as the sigma(L)-dependent bkd and roc operons were most strongly and specifically
      induced after ammonium starvation. These are involved in the uptake and
      utilization of ammonium and alternative nitrogen sources such as amino acids,
      gamma-aminobutyrate, nitrate/nitrite, uric acid/urea and oligopeptides. In
      addition, several carbon catabolite-controlled genes (e.g. acsA, citB), the alpha
      acetolactate synthase/-decarboxylase alsSD operon and several aminotransferase
      genes were specifically induced after ammonium starvation. The induction of
      sigma(F)- and sigma(E)-dependent sporulation proteins at later time points in
      ammonium-starved cells was accompanied by an increased sporulation frequency. The
      specific response to tryptophan starvation includes the TRAP-regulated tryptophan
      biosynthesis genes, some RelA-dependent genes (e.g. adeC, ald) as well as spo0E.
      Furthermore, we recognized overlapping responses between ammonium and tryptophan
      starvation (e.g. dat, maeN) as well as the common induction of the CodY and
      sigma(H) general starvation regulons and the RelA-dependent stringent response.
      Many genes encoding proteins of so far unknown functions could be assigned to
      specifically or commonly induced genes.

PMID- 17183220
TI  - Nitrogen metabolism and nitrogen control in corynebacteria: variations of a
      common theme.
AB  - The published genome sequences of Corynebacterium diphtheriae, Corynebacterium
      efficiens, Corynebacterium glutamicum and Corynebacterium jeikeium were screened
      for genes encoding central components of nitrogen source uptake, nitrogen
      assimilation and nitrogen control systems. Interestingly, the soil-living species
      C. efficiens and C. glutamicum exhibit a broader spectrum of genes for nitrogen
      transport and metabolism than the pathogenic species C. diphtheriae and C.
      jeikeium. The latter are characterized by gene decay and loss of functions like
      urea metabolism and nitrogen-dependent transcription control. The global
      regulator of nitrogen regulation AmtR and its DNA-binding motif are conserved in
      C. diphtheriae, C. efficiens and C. glutamicum, while in C. jeikeium, an AmtR
      encoding gene as well as putative AmtR-binding motifs are missing.

PMID- 17183221
TI  - Nitrogen metabolism in Streptomyces coelicolor: transcriptional and post
      translational regulation.
AB  - Glutamine synthetases (GS) are key enzymes of nitrogen metabolism. Most bacteria
      contain only one type of GS enzyme encoded by glnA. Streptomyces coelicolor, the
      model organism for Gram-positive streptomycetes, however is characterized by two
      functional GS (glnA, glnII) involved in nitrogen assimilation. In addition, three
      GS-like genes were identified which do not exhibit GS enzyme activity. The
      control of nitrogen assimilation and metabolism is mediated by transcriptional
      and post-translational regulation systems. The OmpR-like regulators GlnR and
      GlnRII are involved in transcriptional control of important nitrogen metabolism
      genes (glnA, glnII, amtB, glnK, glnD). Although GlnR and GlnRII share identical
      binding regions, their physiological impact is different. GSI activity is
      modulated post-translationally by the adenylyltransferase GlnE in response to the
      nitrogen concentration whereas no post-translational modifications of GSII are
      known. The PII/GlnD system also responds to changes in nitrogen conditions. The
      adenylyltransferase GlnD, which resembles the uridylyltransferase of
      Enterobacteriaceae, modifies PII under low-nitrogen conditions. Furthermore, PII
      is processed at its N-terminus in response to an ammonium shock. Apparently the
      function of the PII protein of S. coelicolor is different from that of the PII
      proteins of Enterobacteriaceae.

PMID- 17183222
TI  - Regulation of carbon metabolism in the mollicutes and its relation to virulence.
AB  - The mollicutes are cell wall-less bacteria that live in close association with
      their eukaryotic hosts. Their genomes are strongly reduced and so are their
      metabolic capabilities. A survey of the available genome sequences reveals that
      the mollicutes are capable of utilizing sugars as source of carbon and energy via
      glycolysis. The pentose phosphate pathway is incomplete in these bacteria, and
      genes encoding enzymes of the tricarboxylic acid cycle are absent from the
      genomes. Sugars are transported by the phosphotransferase system. As in related
      bacteria, the phosphotransferase system does also seem to play a regulatory role
      in the mollicutes as can be concluded from the functionality of the regulatory
      HPr kinase/phosphorylase. In Mycoplasma pneumoniae, the activity of HPr kinase is
      triggered in the presence of glycerol. This carbon source may be important for
      the mollicutes since it is available in epithelial tissues and its metabolism
      results in the formation of hydrogen peroxide, the major virulence factor of
      several mollicutes. In plant-pathogenic mollicutes such as Spiroplasma citri, the
      regulation of carbon metabolism is crucial in the adaptation to life in plant
      tissues or the insect vectors. Thus, carbon metabolism seems to be intimately
      linked to pathogenicity in the mollicutes.

PMID- 17183223
TI  - Autophagy during conidiation and conidial germination in filamentous fungi.
AB  - Filamentous fungi form aerial hyphae on solid medium, and some of these
      differentiate into conidiophores for asexual sporulation (conidiation). In the
      filamentous deuteromycete, Aspergillus oryzae, aerial hyphae are formed from the
      foot cells and some differentiate into conidiophores, which are composed of
      vesicles, phialides and conidia. Recently, we isolated the yeast ATG8 gene
      homologue Aoatg8 from A. oryzae, and visualized autophagy by the expression of an
      EGFP (enhanced green fluorescent protein)-AoAtg8 fusion protein and DsRed2
      protein in this fungus. Furthermore, by constructing the Aoatg8 deletion and
      conditional mutants, we demonstrated that autophagy functions during the process
      of differentiation of aerial hyphae, conidiation and conidial germination in A.
      oryzae. Here, we discuss the contribution of autophagy towards the
      differentiation and germination processes in filamentous fungi.

PMID- 17183224
TI  - Apoptosis and autophagy function cooperatively for the efficacious execution of
      programmed nurse cell death during Drosophila virilis oogenesis.
AB  - Programmed cell death consists of two major types, apoptotic and autophagic, both
      of which are mainly defined by morphological criteria. Our findings indicate that
      both types of programmed cell death occur in the ovarian nurse cells during
      middle- and late-oogenesis of Drosophila virilis. During mid-oogenesis, the
      spontaneously degenerated egg chambers exhibit typical characteristics of
      apoptotic cell death. Their nurse cells contain condensed chromatin and
      fragmented DNA, whereas active caspase assays and immunostaining procedures
      demonstrate the presence of highly activated caspases. Distinct features of
      autophagic cell death are also observed during D. virilis mid-oogenesis, as shown
      by monodansylcadaverine staining and ultrastructural examination performed by
      transmission electron microscopy. Additionally, atretic egg chambers exhibit an
      accumulation of lysosomal proteases. At the late stages of D. virilis oogenesis,
      apoptosis and autophagy coexist, manifesting cell death features that are similar
      to the ones described above, being also escorted by the involvement of an altered
      cytochrome c conformational display. We propose that apoptosis and autophagy
      operate synergistically during D. virilis oogenesis for a more efficient
      elimination of the degenerated nurse cells.

PMID- 17183225
TI  - Pedal-cycle injuries among children aged <6 years--Wisconsin, 2002-2004.
AB  - Measures to improve pedal-cycle safety and increase helmet use often target
      school-age children rather than younger children, even though preschool children
      wearing helmets have fewer injuries and are more likely to wear helmets in the
      future, compared with children who do not wear helmets. Children aged <6 years
      also use pedal cycles; whether they are passengers on a parent's bicycle, riding
      a tricycle or pedal car, or learning to ride a bicycle, these young cyclists
      often sustain injuries. To provide guidance for intervention strategies targeted
      to young children in Wisconsin, CDC and the Wisconsin Division of Public Health
      analyzed data collected from January 1, 2002 through December 31, 2004, from all
      nonfederal emergency departments (EDs) and hospitals in Wisconsin regarding pedal
      cycle injuries among children aged <6 years. This report describes the results of
      that analysis, which indicated that, during 2002--2004, a total of 2,046 ED
      visits by Wisconsin residents aged <6 years for pedal-cycle injuries occurred;
      for 1,305 (63.8%) of these visits, the primary diagnosis was a head or neck
      injury. These findings underscore the need for interventions designed to reduce
      head and neck injuries in the youngest users of pedal cycles.

PMID- 17183226
TI  - Measles--United States, 2005.
AB  - Measles is a highly infectious, acute viral illness that can be complicated by
      severe pneumonia, diarrhea, and encephalitis and can result in death. In the
      prevaccine era, approximately 500,000 cases of measles occurred annually in the
      United States. During 2005, local and state health departments reported to CDC 66
      confirmed cases of measles (incidence rate: less than one case per 1 million
      population), 34 of which were from a single outbreak in Indiana associated with
      infection in a traveler returning to the United States. This report describes the
      epidemiology of U.S. measles cases in 2005 and documents the absence of endemic
      measles and the continued risk for imported measles infections that can result in
      transmission within the United States. The findings underscore the need to
      maintain the highest possible measles vaccination coverage in the United States
      and to adhere to recommendations regarding measles vaccination.

PMID- 17183227
TI  - Use of cessation methods among smokers aged 16-24 years--United States, 2003.
AB  - Smoking cessation among adolescent smokers is relatively rare, with approximately
      15.6% of smokers aged 12-19 years quitting smoking in a 4-year period
      (approximately 4% per year). Rates for failed quitting attempts among younger
      smokers are higher than those for adults (43%), with approximately 58% of high
      school smokers having tried to quit at least once for 1 day or longer in the
      preceding year. To track the history of quitting behavior among smokers aged 16
      24 years, Roswell Park Cancer Institute (Buffalo, New York) initiated the 2-year
      longitudinal National Youth Smoking Cessation Survey (NYSCS) in 2003. This report
      summarizes key findings from the survey regarding lifetime use of smoking
      cessation methods. The findings indicated that smokers aged 16-24 years who had
      tried to quit were more likely to use unassisted quitting methods than assisted
      quitting methods; none of the unassisted methods are recommended by the Public
      Health Service (PHS) clinical guidelines for treatment of tobacco use and
      dependence, whereas most of the assisted methods are recommended for adults and
      have been determined to be effective. Many youths aged 16-24 years are trying to
      quit smoking but often underestimate the rapid progression to tobacco dependence;
      therefore, PHS clinical practice guidelines for treating tobacco use and
      dependence recommend that certain clinical interventions proven to be effective
      among adults be used in youth-based approaches to cessation. In addition, other
      components of comprehensive tobacco-control programs also increase smoking
      cessation and should be implemented at CDC-recommended levels to lower tobacco
      use among youths and adults.

PMID- 17183228
TI  - CDC's 60th anniversary: director's perspective--James O. Mason, M.D., Dr.P.H.,
      1983-1989.
AB  - The growing momentum toward expanding CDC's responsibilities beyond infectious
      diseases gained strength during the 1980s. Tremendous advances in controlling
      infectious diseases had dramatically reduced illness and death from many long
      standing health threats. In addition, the detrimental effects of chronic and
      other noncommunicable diseases on the nation's health were rapidly increasing.
      Programs to address cancer, heart disease, diabetes, and other leading killers
      became central to CDC's focus. Yet, for much of this decade, a newly emerging
      infectious disease would demand the skills and talents of persons across the
      agency. These new responsibilities led to additional funding, programs, staff,
      and partnerships for the growing agency, while introducing a host of new
      challenges.

PMID- 17183229
TI  - Update: influenza activity--United States, October 1-December 9, 2006.
AB  - During October 1-December 9, 2006, influenza activity remained low in the United
      States overall but increased in southeastern states. This report summarizes U.S.
      influenza activity since October 1, the beginning of the 2006-07 influenza
      season, and updates the previous summary.

PMID- 17183230
TI  - Surveillance for waterborne disease and outbreaks associated with recreational
      water--United States, 2003-2004.
AB  - PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and
      the Council of State and Territorial Epidemiologists have collaboratively
      maintained the Waterborne Disease and Outbreak Surveillance System for collecting
      and reporting waterborne disease and outbreak (WBDO)-related data. In 1978, WBDOs
      associated with recreational water (natural and treated water) were added. This
      system is the primary source of data regarding the scope and effects of WBDOs in
      the United States. REPORTING PERIOD: Data presented summarize WBDOs associated
      with recreational water that occurred during January 2003-December 2004 and one
      previously unreported outbreak from 2002. DESCRIPTION OF THE SYSTEM: Public
      health departments in the states, territories, localities, and the Freely
      Associated States (i.e., the Republic of the Marshall Islands, the Federated
      States of Micronesia, and the Republic of Palau, formerly parts of the U.S.
      administered Trust Territory of the Pacific Islands) have primary responsibility
      for detecting, investigating, and voluntarily reporting WBDOs to CDC. Although
      the surveillance system includes data for WBDOs associated with drinking water,
      recreational water, and water not intended for drinking, only cases and outbreaks
      associated with recreational water are summarized in this report. RESULTS: During
      2003-2004, a total 62 WBDOs associated with recreational water were reported by
      26 states and Guam. Illness occurred in 2,698 persons, resulting in 58
      hospitalizations and one death. The median outbreak size was 14 persons (range: 1
      617 persons). Of the 62 WBDOs, 30 (48.4%) were outbreaks of gastroenteritis that
      resulted from infectious agents, chemicals, or toxins; 13 (21.0%) were outbreaks
      of dermatitis; and seven (11.3%) were outbreaks of acute respiratory illness
      (ARI). The remaining 12 WBDOs resulted in primary amebic meningoencephalitis (n =
      one), meningitis (n = one), leptospirosis (n = one), otitis externa (n = one),
      and mixed illnesses (n = eight). WBDOs associated with gastroenteritis resulted
      in 1,945 (72.1%) of 2,698 illnesses. Forty-three (69.4%) WBDOs occurred at
      treated water venues, resulting in 2,446 (90.7%) cases of illness. The etiologic
      agent was confirmed in 44 (71.0%) of the 62 WBDOs, suspected in 15 (24.2%), and
      unidentified in three (4.8%). Twenty (32.3%) WBDOs had a bacterial etiology; 15
      (24.2%), parasitic; six (9.7%), viral; and three (4.8%), chemical or toxin. Among
      the 30 gastroenteritis outbreaks, Cryptosporidium was confirmed as the causal
      agent in 11 (36.7%), and all except one of these outbreaks occurred in treated
      water venues where Cryptosporidium caused 55.6% (10/18) of the gastroenteritis
      outbreaks. In this report, 142 Vibrio illnesses (reported to the Cholera and
      Other Vibrio Illness Surveillance System) that were associated with recreational
      water exposure were analyzed separately. The most commonly reported species were
      Vibrio vulnificus, V. alginolyticus, and V. parahaemolyticus. V. vulnificus
      illnesses associated with recreational water exposure had the highest Vibrio
      illness hospitalization (87.2%) and mortality (12.8%) rates. INTERPRETATION: The
      number of WBDOs summarized in this report and the trends in recreational water
      associated disease and outbreaks are consistent with previous years. Outbreaks,
      especially the largest ones, are most likely to be associated with summer months,
      treated water venues, and gastrointestinal illness. Approximately 60% of
      illnesses reported for 2003-2004 were associated with the seven largest outbreaks
      (>100 cases). Deficiencies leading to WBDOs included problems with water quality,
      venue design, usage, and maintenance. PUBLIC HEALTH ACTIONS: CDC uses WBDO
      surveillance data to 1) identify the etiologic agents, types of aquatic venues,
      water-treatment systems, and deficiencies associated with outbreaks; 2) evaluate
      the adequacy of efforts (i.e., regulations and public awareness activities) to
      provide safe recreational water; and 3) establish public health prevention
      priorities that might lead to improved regulations and prevention measures at the
      local, state, and federal levels.

PMID- 17183231
TI  - Surveillance for waterborne disease and outbreaks associated with drinking water
      and water not intended for drinking--United States, 2003-2004.
AB  - PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency
      (EPA), and the Council of State and Territorial Epidemiologists have maintained a
      collaborative Waterborne Disease and Outbreaks Surveillance System for collecting
      and reporting data related to occurrences and causes of waterborne disease and
      outbreaks (WBDOs). This surveillance system is the primary source of data
      concerning the scope and effects of WBDOs in the United States. REPORTING PERIOD:
      Data presented summarize 36 WBDOs that occurred during January 2003-December 2004
      and nine previously unreported WBDOs that occurred during 1982-2002. DESCRIPTION
      OF SYSTEM: The surveillance system includes data on WBDOs associated with
      drinking water, water not intended for drinking (excluding recreational water),
      and water of unknown intent. Public health departments in the states,
      territories, localities, and Freely Associated States (i.e., the Republic of the
      Marshall Islands, the Federated States of Micronesia, and the Republic of Palau,
      formerly parts of the U.S.-administered Trust Territory of the Pacific Islands)
      are primarily responsible for detecting and investigating WBDOs and voluntarily
      reporting them to CDC by using a standard form. RESULTS: During 2003-2004, a
      total of 36 WBDOs were reported by 19 states; 30 were associated with drinking
      water, three were associated with water not intended for drinking, and three were
      associated with water of unknown intent. The 30 drinking water-associated WBDOs
      caused illness among an estimated 2,760 persons and were linked to four deaths.
      Etiologic agents were identified in 25 (83.3%) of these WBDOs: 17 (68.0%)
      involved pathogens (i.e., 13 bacterial, one parasitic, one viral, one mixed
      bacterial/parasitic, and one mixed bacterial/parasitic/viral), and eight (32.0%)
      involved chemical/toxin poisonings. Gastroenteritis represented 67.7% of the
      illness related to drinking water-associated WBDOs; acute respiratory illness
      represented 25.8%, and dermatitis represented 6.5%. The classification of
      deficiencies contributing to WBDOs has been revised to reflect the categories of
      concerns associated with contamination at or in the source water, treatment
      facility, or distribution system (SWTD) that are under the jurisdiction of water
      utilities, versus those at points not under the jurisdiction of a water utility
      or at the point of water use (NWU/POU), which includes commercially bottled
      water. A total of 33 deficiencies were cited in the 30 WBDOs associated with
      drinking water: 17 (51.5%) NWU/POU, 14 (42.4%) SWTD, and two (6.1%) unknown. The
      most frequently cited NWU/POU deficiencies involved Legionella spp. in the
      drinking water system (n = eight [47.1%]). The most frequently cited SWTD
      deficiencies were associated with distribution system contamination (n = six
      [42.9%]). Contaminated ground water was a contributing factor in seven times as
      many WBDOs (n = seven) as contaminated surface water (n = one). INTERPRETATION:
      Approximately half (51.5%) of the drinking water deficiencies occurred outside
      the jurisdiction of a water utility in situations not currently regulated by EPA.
      The majority of the WBDOs in which deficiencies were not regulated by EPA were
      associated with Legionella spp. or chemicals/toxins. Problems in the distribution
      system were the most commonly identified deficiencies under the jurisdiction of a
      water utility, underscoring the importance of preventing contamination after
      water treatment. The substantial proportion of WBDOs involving contaminated
      ground water provides support for the Ground Water Rule (finalized in October
      2006), which specifies when corrective action is required for public ground water
      systems. PUBLIC HEALTH ACTIONS: CDC and EPA use surveillance data to identify the
      types of water systems, deficiencies, and etiologic agents associated with WBDOs
      and to evaluate the adequacy of current technologies and practices for providing
      safe drinking water. Surveillance data also are used to establish research
      priorities, which can lead to improved water-quality regulation development. The
      growing proportion of drinking water deficiencies that are not addressed by
      current EPA rules emphasizes the need to address risk factors for water
      contamination in the distribution system and at points not under the jurisdiction
      of water utilities.

PMID- 17183233
TI  - Epidemiology and public health at CDC.
AB  - Epidemiology is the study of the distribution and determinants of health-related
      states or events in specified populations and the application of this study to
      control health problems. However, in public health, the terms "field
      epidemiology" and "applied epidemiology"--which emphasize use of results in
      public health settings--define the practice of epidemiology at CDC. Epidemiology
      has been characterized as the basic science of public health, and its practice at
      CDC has shaped the agency's development and will contribute to its future
      success.

PMID- 17183234
TI  - Laboratory science and public health at CDC.
AB  - Laboratory technology is as essential to public health practitioners for
      monitoring threats to public health as it is to clinical practitioners who depend
      on laboratory technology to diagnose and monitor disease in individuals.
      Laboratory technology provides essential information for effective public health
      interventions, whether monitoring emerging infectious diseases, such as avian
      influenza globally; identifying pathogens, such as Escherichia coli in the U.S.
      food supply and pinpointing its source; screening newborns for devastating
      disorders, such as phenylketonuria, that can be prevented by early intervention;
      or developing the capacity to quickly screen for exposure to chemical and
      biologic agents.

PMID- 17183235
TI  - Veterinary medicine and public health at CDC.
AB  - People readily associate the role of veterinarians with private veterinary
      practice focused on pets and farm animals, but the true dimensions and
      contributions of veterinary medicine are much broader and reflect expanding
      societal needs and contemporary challenges to animal and human health and to the
      environment. Veterinary medicine has responsibilities in biomedical research;
      ecosystem management; public health; food and agricultural systems; and care of
      companion animals, wildlife, exotic animals, and food animals. The expanding role
      of veterinarians at CDC reflects an appreciation for this variety of
      contributions. Veterinarians' educational background in basic biomedical and
      clinical sciences compare with that of physicians. However, unlike their
      counterparts in human medicine, veterinarians must be familiar with multiple
      species, and their training emphasizes comparative medicine. Veterinarians are
      competent in preventive medicine, population health, parasitology, zoonoses, and
      epidemiology, which serve them well for careers in public health. The history and
      tradition of the profession always have focused on protecting and improving both
      animal health and human health.

PMID- 17183236
TI  - Engineering and public health at CDC.
AB  - Engineering is the application of scientific and technical knowledge to solve
      human problems. Using imagination, judgment, and reasoning to apply science,
      technology, mathematics, and practical experience, engineers develop the design,
      production, and operation of useful objects or processes. During the 1940s,
      engineers dominated the ranks of CDC scientists. In fact, the first CDC director,
      Assistant Surgeon General Mark Hollis, was an engineer. CDC engineers were
      involved in malaria control through the elimination of standing water. Eventually
      the CDC mission expanded to include prevention and control of dengue, typhus, and
      other communicable diseases. The development of chlorination, water filtration,
      and sewage treatment were crucial to preventing waterborne illness. Beginning in
      the 1950s, CDC engineers began their work to improve public health while
      developing the fields of environmental health, industrial hygiene, and control of
      air pollution. Engineering disciplines represented at CDC today include
      biomedical, civil, chemical, electrical, industrial, mechanical, mining, and
      safety engineering. Most CDC engineers are located in the National Institute for
      Occupational Safety and Health (NIOSH) and the Agency for Toxic Substances and
      Disease Registry (ATSDR). Engineering research at CDC has a broad stakeholder
      base. With the cooperation of industry, labor, trade associations, and other
      stakeholders and partners, current work includes studies of air contaminants,
      mining, safety, physical agents, ergonomics, and environmental hazards.
      Engineering solutions remain a cornerstone of the traditional "hierarchy of
      controls" approach to reducing public health hazards.

PMID- 17183238
TI  - Genomics and public health at CDC.
AB  - Genomics is the study of the entire genome, including all genes and their
      interactions with each other and with the environment. The scope of public health
      genomics is even broader, encompassing genetic variation in populations, both
      human and microbial. Molecular typing of pathogens--a mainstay of infectious
      disease surveillance, prevention, and control--already is used to trace
      epidemics, provide information for vaccine development, and monitor drug
      resistance. Now genomic research is producing powerful new tools for public
      health; for example, a newly described, microchip-based method promises to
      diagnose influenza infection, distinguish among viruses of human or animal
      origin, and detect mutations that suggest increasing virulence--all in a matter
      of hours.

PMID- 17183239
TI  - Statistics and public health at CDC.
AB  - Since CDC's inception, an important function of the agency has been the
      compilation, analysis, and interpretation of statistical information to guide
      actions and policies to improve health. Sources of data include vital statistics
      records, medical records, personal interviews, telephone and mail surveys,
      physical examinations, and laboratory testing. Public health surveillance data
      have been used to characterize the magnitude and distribution of illness and
      injury; to track health trends; and to develop standard curves, such as growth
      charts. Beyond the development of appropriate program study designs and analytic
      methodologies, statisticians have played roles in the development of public
      health data-collection systems and software to analyze collected data. CDC/ATSDR
      employs approximately 330 mathematical and health statisticians. They work in
      each of the four coordinating centers, two coordinating offices, and the National
      Institute for Occupational Safety and Health.

PMID- 17183240
TI  - Informatics and public health at CDC.
AB  - Since CDC acquired its first mainframe computer in 1964, the use of information
      technology in public health practice has grown steadily and, during the past 2
      decades, dramatically. Public health informatics (PHI) arrived on the scene
      during the 1990s after medical informatics (intersecting information technology,
      medicine, and health care) and bioinformatics (intersecting mathematics,
      statistics, computer science, and molecular biology). Similarly, PHI merged the
      disciplines of information science and computer science to public health
      practice, research, and learning. Using strategies and standards, practitioners
      employ PHI tools and training to maximize health impacts at local, state, and
      national levels. They develop and deploy information technology solutions that
      provide accurate, timely, and secure information to guide public health action.

PMID- 17183241
TI  - Economics and public health at CDC.
AB  - Economics is the study of decisions--the incentives that lead to them and the
      consequences that result from them--as they relate to present and future
      production, distribution, and consumption of goods and services when resources
      are limited and have alternative uses. At CDC, economics is used to
      systematically identify, measure, value, and compare the costs and consequences
      of alternative prevention strategies. Costs and consequences in public health can
      be measured in various ways, including incidence or prevalence of disease;
      numbers of adverse events; utility measures, such as quality-adjusted life years;
      and monetary values. Because it deals with behavior, economics is not really
      about money at all. Money is just a convenient way to measure incentives and
      consequences.

PMID- 17183237
TI  - Behavioral and social sciences and public health at CDC.
AB  - Although the history of CDC spans 60 years, only during the last 2 decades of the
      20th century did the agency come to recognize and better understand the
      importance of the behavioral and social sciences to its overall mission. This
      recognition was a consequence of several events, notably the growing public
      awareness of the many conditions and diseases linked to unhealthy behavior and
      the creation of three new organizational units at CDC--the National Center for
      Chronic Disease Prevention and Health Promotion in 1988, the National Center for
      Injury Prevention and Control in 1992, and the National Center for HIV, STD, and
      TB Prevention in 1993--that focused on conditions, diseases, and injuries with
      clear behavioral risks. Accordingly, the relatively small number of CDC
      behavioral and social scientists were initially concentrated in these three
      centers. In 1995, to raise awareness of behavioral and social sciences at CDC and
      to integrate these fields into CDC-conducted and -supported research and practice
      activities, the agency's behavioral and social scientists established the
      Behavioral and Social Sciences Working Group (BSSWG). The application of the
      behavioral and social science disciplines to public health attests to the success
      of the working group. Today, BSSWG continues as a formal organization sponsored
      by the Office of the Chief Science Officer within the CDC Office of the Director.

PMID- 17183242
TI  - Law and public health at CDC.
AB  - Public health law is an emerging field in U.S. public health practice. The 20th
      century proved the indispensability of law to public health, as demonstrated by
      the contribution of law to each of the century's 10 great public health
      achievements. Former CDC Director Dr. William Foege has suggested that law, along
      with epidemiology, is an essential tool in public health practice. Public health
      laws are any laws that have important consequences for the health of defined
      populations. They derive from federal and state constitutions; statutes, and
      other legislative enactments; agency rules and regulations; judicial rulings and
      case law; and policies of public bodies. Government agencies that apply public
      health laws include agencies officially designated as "public health agencies,"
      as well as health-care, environmental protection, education, and law enforcement
      agencies, among others.

PMID- 17183243
TI  - Urban planning and public health at CDC.
AB  - Urban planning, also called city and regional planning, is a multidisciplinary
      field in which professionals work to improve the welfare of persons and
      communities by creating more convenient, equitable, healthful, efficient, and
      attractive places now and for the future. The centerpiece of urban planning
      activities is a "master plan," which can take many forms, including comprehensive
      plans, neighborhood plans, community action plans, regulatory and incentive
      strategies, economic development plans, and disaster preparedness plans.
      Traditionally, these plans include assessing and planning for community needs in
      some or all of the following areas: transportation, housing, commercial/office
      buildings, natural resource utilization, environmental protection, and health
      care infrastructure. Urban planning and public health share common missions and
      perspectives. Both aim to improve human well-being, emphasize needs assessment
      and service delivery, manage complex social systems, focus at the population
      level, and rely on community-based participatory methods. Both fields focus on
      the needs of vulnerable populations. Throughout their development, both fields
      have broadened their perspectives. Initially, public health most often used a
      biomedical model (examining normal/abnormal functioning of the human organism),
      and urban planning often relied on a geographic model (analysis of human needs or
      interactions in a spatial context). However, both fields have expanded their
      tools and perspectives, in part because of the influence of the other. Urban
      planning and public health have been intertwined for most of their histories. In
      1854, British physician John Snow used geographic mapping of an outbreak of
      cholera in London to identify a public water pump as the outbreak's source.
      Geographic analysis is a key planning tool shared by urban planning and public
      health. In the mid-1800s, planners such as Frederick Law Olmsted bridged the gap
      between the fields by advancing the concept that community design contributes to
      physical and mental health; serving as President Lincoln's U.S. Sanitary
      Commission Secretary; and designing hundreds of places, including New York's
      Central Park. By 1872, the disciplines were so aligned that two of the seven
      founders of the American Public Health Association were urban designers (an
      architect and a housing specialist). In 1926, the U.S. Supreme Court, in
      validating zoning and land-use law as a legal government authority in Village of
      Euclid v. Ambler Realty, cited the protection of public health as part of its
      justification. Other connections have included 1) pioneering urbanist Jane
      Jacobs, who during the 1960s, called for community design that offered safe and
      convenient options for walking, biking, and impromptu social interaction; and 2)
      the Healthy Cities movement, which began in Europe and the United States during
      the 1980s and now includes projects in approximately 1,000 cities that in various
      ways highlight the role of health as much more than the presence of medical care.

PMID- 17183244
TI  - Uroplakins: new molecular players in the biology of urinary tract malformations.
AB  - The uroplakins (UPs) are a family of proteins which associate with each other and
      form plaques on the apical surface of the urothelium. These plaques contribute to
      a permeability barrier, preventing the influx of urine from the urinary tract
      lumen. Urinary tract malformations associated with human and mouse UP mutations,
      the human fetal expression patterns of UPs and experiments in Xenopus oocytes are
      collectively revealing new functions for the UPs, forcing us to view these
      proteins in a new light. Rather than simply being products of the urothelial
      differentiation program, they may be a group of proteins central to the process
      of urinary tract differentiation itself.

PMID- 17183245
TI  - Gene expression profiles of human proximal tubular epithelial cells in
      proteinuric nephropathies.
AB  - In kidney disease renal proximal tubular epithelial cells (RPTEC) actively
      contribute to the progression of tubulointerstitial fibrosis by mediating both an
      inflammatory response and via epithelial-to-mesenchymal transition. Using laser
      capture microdissection we specifically isolated RPTEC from cryosections of the
      healthy parts of kidneys removed owing to renal cell carcinoma and from kidney
      biopsies from patients with proteinuric nephropathies. RNA was extracted and
      hybridized to complementary DNA microarrays after linear RNA amplification.
      Statistical analysis identified 168 unique genes with known gene ontology
      association, which separated patients from controls. Besides distinct alterations
      in signal-transduction pathways (e.g. Wnt signalling), functional annotation
      revealed a significant upregulation of genes involved in cell proliferation and
      cell cycle control (like insulin-like growth factor 1 or cell division cycle 34),
      cell differentiation (e.g. bone morphogenetic protein 7), immune response,
      intracellular transport and metabolism in RPTEC from patients. On the contrary we
      found differential expression of a number of genes responsible for cell adhesion
      (like BH-protocadherin) with a marked downregulation of most of these
      transcripts. In summary, our results obtained from RPTEC revealed a differential
      regulation of genes, which are likely to be involved in either pro-fibrotic or
      tubulo-protective mechanisms in proteinuric patients at an early stage of kidney
      disease.

PMID- 17183246
TI  - Kidney function and markers of inflammation in elderly persons without chronic
      kidney disease: the health, aging, and body composition study.
AB  - Inflammatory markers are elevated in persons with estimated glomerular filtration
      rates less than 60 ml/min/1.73 m2. As cystatin C may detect small changes in
      kidney function not detected by estimated glomerular filtration rate, we
      evaluated the association between cystatin C and serum markers of inflammation in
      older adults with estimated glomerular filtration rate >or=60. This is an
      analysis using measures from the Health, Aging, and Body Composition Study, a
      cohort of well-functioning adults aged 70-79 years. Cystatin C correlated with
      all five inflammatory biomarkers: C-reactive protein (r=0.08), interleukin-6
      (r=0.19), tumor necrosis factor alpha (TNF-alpha) (r=0.41), soluble TNF receptor
      1 (STNF-R1) (r=0.61), and soluble TNF receptor 2 (STNF-R2) (r=0.54); P<0.0005 for
      all. In adjusted analyses, cystatin C concentrations appeared to have stronger
      associations with each biomarker compared with estimated glomerular filtration
      rate or serum creatinine. Participants with a cystatin C>or=1.0 mg/l had
      significantly higher levels of all five biomarkers compared to those with a
      cystatin C<1.0 (mean differences ranging 16-29%, all P<0.05). Cystatin C has a
      linear association with inflammatory biomarkers in an ambulatory elderly cohort
      with estimated glomerular filtration rates >or=60; associations are particularly
      strong with TNF-alpha and the STNF-R.

PMID- 17183247
TI  - Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in
      kidneys with glomerular disease.
AB  - The cell cycle inhibitor p16(INK4A) (also known as cyclin-dependent kinase
      inhibitor 2A) is expressed in vivo in many tissues with age. The exposure of
      certain chronic stresses can trigger p16(INK4A) expression and a senescence-like
      phenotype. We studied whether p16(INK4A) expression is induced in glomerular
      disease (GD). We performed p16(INK4A) immunostaining on 35 biopsies with GD, 12
      tubulointerstitial nephritis (TIN), and 19 normal live donor kidneys at
      transplantation. Based on values for 42 normal kidneys, we calculated expected
      nuclear p16(INK4A) expression for age and compared the observed values in
      diseased kidneys to those expected for age. In GD, p16(INK4A) expression was
      strikingly increased in glomerular and interstitial cell nuclei compared to
      normals and TIN, and could not be attributed to age (P<0.05). By multivariate
      analyses, GD was independently associated with increased nuclear p16(INK4a)
      expression in glomeruli (P<0.001) and interstitium (P=0.01). The p16(INK4A)
      expression in glomerular and interstitial cell nuclei, and tubular cytoplasm was
      higher in kidneys with proteinuria and with atrophy/fibrosis (P<0.05). Older age
      was associated with increased nuclear p16(INK4a) expression in tubules (P=0.01),
      and interstitial inflammation was associated with increased nuclear p16(INK4a)
      expression in interstitial cells (P=0.001). The p16(INK4a) staining in tubular
      cytoplasm was increased in both GD and TIN compared to normals (P<0.001), and was
      not related to age (P>0.05). Thus, kidneys with GD display increased expression
      of senescence marker p16(INK4A) in glomerular and interstitial cell nuclei
      compared to kidneys with normal aging or TIN. The findings suggest a role for
      somatic cell senescence mechanisms in progression of GD.

PMID- 17183248
TI  - Cost of applying the K/DOQI guidelines for bone metabolism and disease to a
      cohort of chronic hemodialysis patients.
AB  - Hyperphosphatemia is a common feature of advanced chronic kidney disease (CKD)
      and is treated routinely with oral calcium-based phosphate binders. In 2003, the
      National Kidney Foundation Kidney Disease Outcomes and Quality Initiative
      (K/DOQI) published Clinical Practice Guidelines (CPGs) for the treatment of Bone
      Metabolism and Disease in CKD. These advocate broad usage of expensive non
      calcium-based phosphate binders such as sevelamer. This study was designed to
      determine the cost of implementation of the K/DOQI CPGs as they pertain to
      phosphate binding in a large Canadian hemodialysis (HD) unit. Laboratory and
      medication data for all chronic HD patients at the Ottawa Hospital were reviewed
      (n=416). Patients meeting each of the relevant K/DOQI guidelines were identified.
      Where guidelines would recommend a switch to non-calcium binders, equivalent
      sevelamer doses were estimated. The cost of implementing each guideline was then
      calculated individually and an estimate total cost of implementing all the
      guidelines was derived. Overall, 53% (222) patients fulfilled at least one
      criterion for sevelamer use. The yearly cost of implementation of the K/DOQI
      guidelines at this center was estimated at 500,605 dollars (American dollars).
      Given the significant cost, widespread adoption of the K/DOQI CPGs for Bone
      Metabolism and Disease should await the publication of compelling data
      demonstrating significant improved outcomes in patients treated with sevelamer.

PMID- 17183250
TI  - The ISN's Sister Renal Center program.

PMID- 17183249
TI  - Chronic metabolic acidosis alters osteoblast differentiation from human
      mesenchymal stem cells.
AB  - Bone histology of distal renal tubular acidosis patients showed decreased bone
      formation with impaired bone matrix mineralization that is not entirely explained
      by an alteration in the mineral balance. Data from in vitro studies suggests a
      direct inhibitory effect of metabolic acidosis on osteoblast function. We
      investigated the effects of chronic metabolic acidosis on osteoblast
      differentiation from mesenchymal stem cells (MSCs). Human MSCs were allowed to
      differentiate into osteoblasts in culture. Concentrated hydrochloric acid was
      added to the medium to lower the bicarbonate concentration and pH. The expression
      of various osteoblastic genes and proteins and bone matrix mineralization were
      examined. Chronic metabolic acidosis enhanced the messenger RNA (mRNA) and
      protein expression of early osteoblast transcription factor, runx-2, whereas
      inhibiting osterix and having no effect on ATF-4. The expression of type I
      collagen, the most abundant bone matrix protein, was increased following the same
      pattern of runx-2. Likewise, metabolic acidosis slightly enhanced the expression
      of mature osteoblastic gene, osteocalcin. Study on mineralization revealed
      suppressed alkaline phosphatase mRNA and enzyme activity. Despite the augmented
      collagen deposit in acidic culture, bone matrix mineralization was impaired. In
      conclusion, chronic metabolic acidosis alters osteoblast differentiation from
      MSCs through its diverse effect on osteoblastic genes and proteins resulting in
      an impairment of bone formation.

PMID- 17183251
TI  - A new look at an old problem: therapy of chronic hyponatremia.

PMID- 17183252
TI  - European Best Practice Guidelines for Peritoneal Dialysis acknowledged by ISN.

PMID- 17183253
TI  - Superimposing candesartan onto ACE inhibition slows renal function decline in
      nondiabetic chronic kidney disease.

PMID- 17183254
TI  - Benefit of acetylcysteine for prevention of contrast-induced nephropathy after
      primary angioplasty.

PMID- 17183255
TI  - Optimal paricalcitol starting dose for parathyroid hormone suppression in
      secondary hyperparathyroidism.

PMID- 17183256
TI  - Predicting outcomes of peritoneal-dialysis-associated peritonitis based on
      dialysate white blood cell count.

PMID- 17183257
TI  - Is it premature to use calcineurin-inhibitor-free immunosuppression in pediatric
      renal transplantation?

PMID- 17183258
TI  - When should post-transplantation proteinuria be attributed to the renal allograft
      rather than to the native kidney?

PMID- 17183259
TI  - Anemia in diabetes: marker or mediator of microvascular disease?
AB  - Anemia is a common finding in patients with diabetes due to the high burden of
      chronic kidney disease in this population. Anemia is more prevalent and is found
      earlier in patients with diabetes than in those with kidney disease from other
      causes. The increased risk of anemia in diabetes probably reflects changes in the
      renal tubulointerstitium associated with diabetic kidney disease, which disrupt
      the delicate interaction between interstitial fibroblasts, capillaries and
      tubular cells required for normal hemopoietic function. In particular, the
      uncoupling of the hemoglobin concentration from renal erythropoietin synthesis
      seems to be the key factor underlying the development of anemia. Systemic
      inflammation, functional hematinic deficiencies, erythropoietin resistance and
      reduced red cell survival also drive anemia in the setting of impaired renal
      compensation. Although anemia can be considered a marker of kidney damage,
      reduced hemoglobin levels independently identify diabetic patients with an
      increased risk of microvascular complications, cardiovascular disease and
      mortality. Nevertheless, a direct role in the development or progression of
      diabetic complications remains to be clearly established and the clinical utility
      of correcting anemia in diabetic patients has yet to be demonstrated in
      randomized controlled trials. Correction of anemia certainly improves performance
      and quality of life in diabetic patients. In the absence of additional data,
      treatment should be considered palliative, and any functional benefits must be
      matched against costs to the patient and the health system.

PMID- 17183260
TI  - Living donor renal transplantation: recent developments and perspectives.
AB  - Renal transplantation is the optimal treatment for patients of all ages with end
      stage renal disease. Life expectancy of the population in general is increasing
      consistently, as is the age of the dialysis population. Consequently, the average
      ages of kidney donors and recipients are rising. The combination of a growing
      number of patients with end-stage renal disease and a shortage of organs poses a
      significant challenge to the transplant community. Donor shortage is associated
      with unfavorable consequences (e.g. prolonged waiting time, and compromised graft
      and patient survival). As such, multidirectional efforts are required to expand
      the donor pool. Increasing the frequency of living donation seems to be an
      efficient solution. Living donation is associated with superior results for the
      recipient, and relatively benign long-term outcomes for donors. Reluctance to use
      organs from living donors whose eligibility was previously considered marginal
      (e.g. elderly donors) is declining. Although increased donor age is associated
      with reduced graft survival rates, this should not preclude use of older living
      donors; transplantation is definitely superior to remaining on dialysis.
      Thorough, standardized evaluation and careful screening for premorbid conditions
      in both elderly donors and elderly recipients are essential. Here, we present
      various options for expanding the living donor pool, with emphasis on the
      utilization of elderly living donors and transplantation in elderly recipients.

PMID- 17183261
TI  - Mechanisms of disease: The role of aldosterone in kidney damage and clinical
      benefits of its blockade.
AB  - In the past 10 years, many widely accepted concepts relating to aldosterone
      production and its pathogenetic role have changed. We now know that aldosterone
      is produced not only by the zona glomerulosa of the adrenal cortex, but also in
      the heart, blood vessels, kidney and brain; such extra-epithelial production
      occurs mainly during tissue repair. Also, increased aldosterone levels contribute
      to vessel inflammation, oxidative stress, endothelial dysfunction and organ
      damage. As such, aldosterone has a key role in the development of myocardial
      fibrosis. Anti-aldosterone treatment has proven effective in patients with heart
      failure. Experimental evidence regarding the role of aldosterone in kidney damage
      has accumulated. Aldosterone infusion can counteract the beneficial effects of
      treatment with angiotensin-converting-enzyme inhibitors, causing more-severe
      proteinuria and an increased number of vascular and glomerular lesions; treatment
      with aldosterone antagonists can reverse these alterations. Preliminary
      observations in pilot studies in humans confirm the experimental findings,
      supporting the hypothesis that aldosterone antagonists are renoprotective in
      clinical practice. Studies in larger populations with longer follow-up are needed
      to confirm this theory.

PMID- 17183262
TI  - Idiopathic hypocomplementemic immune-complex-mediated tubulointerstitial
      nephritis.
AB  - BACKGROUND: A 42-year-old man presenting with flank pain was found to have renal
      failure with severe hypocomplementemia and eosinophilia. INVESTIGATIONS: Physical
      examination, laboratory testing, renal ultrasonography, and renal biopsies.
      DIAGNOSIS: Acute immune-complex-mediated tubulointerstitial nephritis.
      MANAGEMENT: Immunosuppressive therapy with 1 mg/kg/day prednisone.

PMID- 17183263
TI  - Evolutionary biology: oxygen at life's boundaries.

PMID- 17183264
TI  - Palaeontology: embryonic identity crisis.

PMID- 17183265
TI  - Transcription factor control of asymmetric cell divisions that establish the
      stomatal lineage.
AB  - The establishment of new cell lineages during development often requires a
      symmetry-breaking event. An asymmetric division in the epidermis of plants
      initiates a lineage that ultimately produces stomatal guard cells. Stomata are
      pores in the epidermis that serve as the main conduits for gas exchange between
      plants and the atmosphere; they are critical for photosynthesis and exert a major
      influence on global carbon and water cycles. Recent studies implicated
      intercellular signalling in preventing the inappropriate production of stomatal
      complexes. Genes required to make stomata, however, remained elusive. Here we
      report the identification of a gene, SPEECHLESS (SPCH), encoding a basic helix
      loop-helix (bHLH) transcription factor that is necessary and sufficient for the
      asymmetric divisions that establish the stomatal lineage in Arabidopsis thaliana.
      We demonstrate that SPCH and two paralogues are successively required for the
      initiation, proliferation and terminal differentiation of cells in the stomatal
      lineage. The stomatal bHLHs define a molecular pathway sufficient to create one
      of the key cell types in plants. Similar molecules and regulatory mechanisms are
      used during muscle and neural development, highlighting a conserved use of
      closely related bHLHs for cell fate specification and differentiation.

PMID- 17183266
TI  - Categorization of behavioural sequences in the prefrontal cortex.
AB  - Although it has long been thought that the prefrontal cortex of primates is
      involved in the integrative regulation of behaviours, the neural architecture
      underlying specific aspects of cognitive behavioural planning has yet to be
      clarified. If subjects are required to remember a large number of complex motor
      sequences and plan to execute each of them individually, categorization of the
      sequences according to the specific temporal structure inherent in each subset of
      sequences serves to facilitate higher-order planning based on memory. Here we
      show, using these requirements, that cells in the lateral prefrontal cortex
      selectively exhibit activity for a specific category of behavioural sequences,
      and that categories of behaviours, embodied by different types of movement
      sequences, are represented in prefrontal cells during the process of planning.
      This cellular activity implies the generation of neural representations capable
      of storing structured event complexes at an abstract level, exemplifying the
      development of macro-structured action knowledge in the lateral prefrontal
      cortex.

PMID- 17183267
TI  - Termination of asymmetric cell division and differentiation of stomata.
AB  - Stomata consist of a pair of guard cells that mediate gas and water-vapour
      exchange between plants and the atmosphere. Stomatal precursor cells-meristemoids
      possess a transient stem-cell-like property and undergo several rounds of
      asymmetric divisions before further differentiation. Here we report that the
      Arabidopsis thaliana basic helix-loop-helix (bHLH) protein MUTE is a key switch
      for meristemoid fate transition. In the absence of MUTE, meristemoids abort after
      excessive asymmetric divisions and fail to differentiate stomata. Constitutive
      overexpression of MUTE directs the entire epidermis to adopt guard cell identity.
      MUTE has two paralogues: FAMA, a regulator of guard cell morphogenesis, and
      SPEECHLESS (SPCH). We show that SPCH directs the first asymmetric division that
      initiates stomatal lineage. Together, SPCH, MUTE and FAMA bHLH proteins control
      stomatal development at three consecutive steps: initiation, meristemoid
      differentiation and guard cell morphogenesis. Our findings highlight the roles of
      closely related bHLHs in cell type differentiation in plants and animals.

PMID- 17183268
TI  - Evidence of giant sulphur bacteria in Neoproterozoic phosphorites.
AB  - In situ phosphatization and reductive cell division have recently been discovered
      within the vacuolate sulphur-oxidizing bacteria. Here we show that certain
      Neoproterozoic Doushantuo Formation (about 600 million years bp) microfossils,
      including structures previously interpreted as the oldest known metazoan eggs and
      embryos, can be interpreted as giant vacuolate sulphur bacteria. Sulphur bacteria
      of the genus Thiomargarita have sizes and morphologies similar to those of many
      Doushantuo microfossils, including symmetrical cell clusters that result from
      multiple stages of reductive division in three planes. We also propose that
      Doushantuo phosphorite precipitation was mediated by these bacteria, as shown in
      modern Thiomargarita-associated phosphogenic sites, thus providing the taphonomic
      conditions that preserved other fossils known from the Doushantuo Formation.

PMID- 17183269
TI  - Oxygen content of transmembrane proteins over macroevolutionary time scales.
AB  - We observe that the time of appearance of cellular compartmentalization
      correlates with atmospheric oxygen concentration. To explore this correlation, we
      predict and characterize the topology of all transmembrane proteins in 19 taxa
      and correlate differences in topology with historical atmospheric oxygen
      concentrations. Here we show that transmembrane proteins, individually and as a
      group, were probably selectively excluding oxygen in ancient ancestral taxa, and
      that this constraint decreased over time when atmospheric oxygen levels rose. As
      this constraint decreased, the size and number of communication-related
      transmembrane proteins increased. We suggest the hypothesis that atmospheric
      oxygen concentrations affected the timing of the evolution of cellular
      compartmentalization by constraining the size of domains necessary for
      communication across membranes.

PMID- 17183274
TI  - Peer review and fraud.

PMID- 17183275
TI  - Kyoto for commuters.

PMID- 17183270
TI  - Toxoplasma co-opts host gene expression by injection of a polymorphic kinase
      homologue.
AB  - Toxoplasma gondii, an obligate intracellular parasite of the phylum Apicomplexa,
      can cause severe disease in humans with an immature or suppressed immune system.
      The outcome of Toxoplasma infection is highly dependent on the strain type, as
      are many of its in vitro growth properties. Here we use genetic crosses between
      type II and III lines to show that strain-specific differences in the modulation
      of host cell transcription are mediated by a putative protein kinase, ROP16. Upon
      invasion by the parasite, this polymorphic protein is released from the apical
      organelles known as rhoptries and injected into the host cell, where it
      ultimately affects the activation of signal transducer and activator of
      transcription (STAT) signalling pathways and consequent downstream effects on a
      key host cytokine, interleukin (IL)-12. Our findings provide a new mechanism for
      how an intracellular eukaryotic pathogen can interact with its host and reveal
      important differences in how different Toxoplasma lineages have evolved to
      exploit this interaction.

PMID- 17183279
TI  - Gravity probe falters.

PMID- 17183278
TI  - Climate credits.

PMID- 17183280
TI  - Green activists enlist penguins to save the world.

PMID- 17183281
TI  - Animal experiments under fire for poor design.

PMID- 17183282
TI  - NIH offers free access to wealth of disease data.

PMID- 17183286
TI  - 2006 Gallery: brilliant display.

PMID- 17183287
TI  - Better, faster--and easier to use.

PMID- 17183288
TI  - Human evolution: how Africa learned to love the cow.

PMID- 17183289
TI  - Oceanography: creating the perfect wave.

PMID- 17183290
TI  - Physiology: freaks of nature?

PMID- 17183295
TI  - Measures for measures.

PMID- 17183300
TI  - Physiology: obesity and gut flora.

PMID- 17183301
TI  - Astrophysics: a burst of new ideas.

PMID- 17183303
TI  - Particle Physics: neutrons radiating decay.

PMID- 17183302
TI  - Neurobiology: auditory fidelity.

PMID- 17183304
TI  - Ageing: too fast by mistake.

PMID- 17183305
TI  - Optics: a light touch.

PMID- 17183306
TI  - Mathematics: proof at a roll of the dice.

PMID- 17183308
TI  - Parthenogenesis in Komodo dragons.
AB  - Parthenogenesis, the production of offspring without fertilization by a male, is
      rare in vertebrate species, which usually reproduce after fusion of male and
      female gametes. Here we use genetic fingerprinting to identify parthenogenetic
      offspring produced by two female Komodo dragons (Varanus komodoensis) that had
      been kept at separate institutions and isolated from males; one of these females
      subsequently produced additional offspring sexually. This reproductive plasticity
      indicates that female Komodo dragons may switch between asexual and sexual
      reproduction, depending on the availability of a mate--a finding that has
      implications for the breeding of this threatened species in captivity. Most zoos
      keep only females, with males being moved between zoos for mating, but perhaps
      they should be kept together to avoid triggering parthenogenesis and thereby
      decreasing genetic diversity.

PMID- 17183309
TI  - Microbial ecology: human gut microbes associated with obesity.
AB  - Two groups of beneficial bacteria are dominant in the human gut, the
      Bacteroidetes and the Firmicutes. Here we show that the relative proportion of
      Bacteroidetes is decreased in obese people by comparison with lean people, and
      that this proportion increases with weight loss on two types of low-calorie diet.
      Our findings indicate that obesity has a microbial component, which might have
      potential therapeutic implications.

PMID- 17183310
TI  - Biomechanics: rubber bands reduce the cost of carrying loads.
AB  - Vertical movement of the hip during locomotion causes a loaded backpack to be
      accelerated with each step, which imposes large peak forces on the wearer. Here
      we show that using bungee cords to suspend the load from a backpack frame reduces
      not only its vertical movement, and hence its vertical force on the carrier, but
      also the energetic cost of walking with the pack. This permits larger loads to be
      carried while moving rapidly, and at the same time reduces the risk of
      orthopaedic and muscular injury.

PMID- 17183311
TI  - Olfaction: underwater 'sniffing' by semi-aquatic mammals.
AB  - Terrestrial species that forage underwater face challenges because their body
      parts and senses are adapted for land--for example, it is widely held that
      mammals cannot use olfaction underwater because it is impossible for them to
      inspire air (sniff) to convey odorants to the olfactory epithelium. Here I
      describe a mechanism for underwater sniffing used by the semi-aquatic star-nosed
      mole (Condylura cristata) and water shrew (Sorex palustris). While underwater,
      both species exhale air bubbles onto objects or scent trails and then re-inspire
      the bubbles to carry the smell back through the nose. This newly described
      behaviour provides a mechanism for mammalian olfaction underwater.

PMID- 17183312
TI  - An obesity-associated gut microbiome with increased capacity for energy harvest.
AB  - The worldwide obesity epidemic is stimulating efforts to identify host and
      environmental factors that affect energy balance. Comparisons of the distal gut
      microbiota of genetically obese mice and their lean littermates, as well as those
      of obese and lean human volunteers have revealed that obesity is associated with
      changes in the relative abundance of the two dominant bacterial divisions, the
      Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and
      biochemical analyses that these changes affect the metabolic potential of the
      mouse gut microbiota. Our results indicate that the obese microbiome has an
      increased capacity to harvest energy from the diet. Furthermore, this trait is
      transmissible: colonization of germ-free mice with an 'obese microbiota' results
      in a significantly greater increase in total body fat than colonization with a
      'lean microbiota'. These results identify the gut microbiota as an additional
      contributing factor to the pathophysiology of obesity.

PMID- 17183313
TI  - Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis.
AB  - Tumour growth requires accompanying expansion of the host vasculature, with
      tumour progression often correlated with vascular density. Vascular endothelial
      growth factor (VEGF) is the best-characterized inducer of tumour angiogenesis. We
      report that VEGF dynamically regulates tumour endothelial expression of Delta
      like ligand 4 (Dll4), which was previously shown to be absolutely required for
      normal embryonic vascular development. To define Dll4 function in tumour
      angiogenesis, we manipulated this pathway in murine tumour models using several
      approaches. Here we show that blockade resulted in markedly increased tumour
      vascularity, associated with enhanced angiogenic sprouting and branching.
      Paradoxically, this increased vascularity was non-productive-as shown by poor
      perfusion and increased hypoxia, and most importantly, by decreased tumour growth
      even for tumours resistant to anti-VEGF therapy. Thus, VEGF-induced Dll4 acts as
      a negative regulator of tumour angiogenesis; its blockade results in a striking
      uncoupling of tumour growth from vessel density, presenting a novel therapeutic
      approach even for tumours resistant to anti-VEGF therapies.

PMID- 17183314
TI  - A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph
      axis.
AB  - XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA lesions and
      cytotoxic DNA interstrand crosslinks. Mild mutations in XPF cause the cancer
      prone syndrome xeroderma pigmentosum. A patient presented with a severe XPF
      mutation leading to profound crosslink sensitivity and dramatic progeroid
      symptoms. It is not known how unrepaired DNA damage accelerates ageing or its
      relevance to natural ageing. Here we show a highly significant correlation
      between the liver transcriptome of old mice and a mouse model of this progeroid
      syndrome. Expression data from XPF-ERCC1-deficient mice indicate increased cell
      death and anti-oxidant defences, a shift towards anabolism and reduced growth
      hormone/insulin-like growth factor 1 (IGF1) signalling, a known regulator of
      lifespan. Similar changes are seen in wild-type mice in response to chronic
      genotoxic stress, caloric restriction, or with ageing. We conclude that
      unrepaired cytotoxic DNA damage induces a highly conserved metabolic response
      mediated by the IGF1/insulin pathway, which re-allocates resources from growth to
      somatic preservation and life extension. This highlights a causal contribution of
      DNA damage to ageing and demonstrates that ageing and end-of-life fitness are
      determined both by stochastic damage, which is the cause of functional decline,
      and genetics, which determines the rates of damage accumulation and decline.

PMID- 17183315
TI  - A new gamma-ray burst classification scheme from GRB 060614.
AB  - Gamma-ray bursts (GRBs) are known to come in two duration classes, separated at
      approximately 2 s. Long-duration bursts originate from star-forming regions in
      galaxies, have accompanying supernovae when these are near enough to observe and
      are probably caused by massive-star collapsars. Recent observations show that
      short-duration bursts originate in regions within their host galaxies that have
      lower star-formation rates, consistent with binary neutron star or neutron star
      black hole mergers. Moreover, although their hosts are predominantly nearby
      galaxies, no supernovae have been so far associated with short-duration GRBs.
      Here we report that the bright, nearby GRB 060614 does not fit into either class.
      Its approximately 102-s duration groups it with long-duration GRBs, while its
      temporal lag and peak luminosity fall entirely within the short-duration GRB
      subclass. Moreover, very deep optical observations exclude an accompanying
      supernova, similar to short-duration GRBs. This combination of a long-duration
      event without an accompanying supernova poses a challenge to both the collapsar
      and the merging-neutron-star interpretations and opens the door to a new GRB
      classification scheme that straddles both long- and short-duration bursts.

PMID- 17183316
TI  - No supernovae associated with two long-duration gamma-ray bursts.
AB  - It is now accepted that long-duration gamma-ray bursts (GRBs) are produced during
      the collapse of a massive star. The standard 'collapsar' model predicts that a
      broad-lined and luminous type Ic core-collapse supernova accompanies every long
      duration GRB. This association has been confirmed in observations of several
      nearby GRBs. Here we report that GRB 060505 (ref. 10) and GRB 060614 (ref. 11)
      were not accompanied by supernova emission down to limits hundreds of times
      fainter than the archetypal supernova SN 1998bw that accompanied GRB 980425, and
      fainter than any type Ic supernova ever observed. Multi-band observations of the
      early afterglows, as well as spectroscopy of the host galaxies, exclude the
      possibility of significant dust obscuration and show that the bursts originated
      in actively star-forming regions. The absence of a supernova to such deep limits
      is qualitatively different from all previous nearby long-duration GRBs and
      suggests a new phenomenological type of massive stellar death.

PMID- 17183317
TI  - An enigmatic long-lasting gamma-ray burst not accompanied by a bright supernova.
AB  - Gamma-ray bursts (GRBs) are short, intense flashes of soft gamma-rays coming from
      the distant Universe. Long-duration GRBs (those lasting more than approximately 2
      s) are believed to originate from the deaths of massive stars, mainly on the
      basis of a handful of solid associations between GRBs and supernovae. GRB 060614,
      one of the closest GRBs discovered, consisted of a 5-s hard spike followed by
      softer, brighter emission that lasted for approximately 100 s (refs 8, 9). Here
      we report deep optical observations of GRB 060614 showing no emerging supernova
      with absolute visual magnitude brighter than M(V) = -13.7. Any supernova
      associated with GRB 060614 was therefore at least 100 times fainter, at optical
      wavelengths, than the other supernovae associated with GRBs. This demonstrates
      that some long-lasting GRBs can either be associated with a very faint supernova
      or produced by different phenomena.

PMID- 17183318
TI  - A novel explosive process is required for the gamma-ray burst GRB 060614.
AB  - Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has
      progressed rapidly, thanks to the discovery and observation of their long-lived
      afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive
      deaths of massive stars ('collapsars', ref. 1), which produce accompanying
      supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which
      has been argued to be the merger of two compact objects. Here we report optical
      observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out
      the presence of an associated supernova. This would seem to require a new
      explosive process: either a massive collapsar that powers a GRB without any
      associated supernova, or a new type of 'engine', as long-lived as the collapsar
      but without a massive star. We also show that the properties of the host galaxy
      (redshift z = 0.125) distinguish it from other long-duration GRB hosts and
      suggest that an entirely new type of GRB progenitor may be required.

PMID- 17183319
TI  - A deep dynamo generating Mercury's magnetic field.
AB  - Mercury has a global magnetic field of internal origin and it is thought that a
      dynamo operating in the fluid part of Mercury's large iron core is the most
      probable cause. However, the low intensity of Mercury's magnetic field--about 1%
      the strength of the Earth's field--cannot be reconciled with an Earth-like
      dynamo. With the common assumption that Coriolis and Lorentz forces balance in
      planetary dynamos, a field thirty times stronger is expected. Here I present a
      numerical model of a dynamo driven by thermo-compositional convection associated
      with inner core solidification. The thermal gradient at the core-mantle boundary
      is subadiabatic, and hence the outer region of the liquid core is stably
      stratified with the dynamo operating only at depth, where a strong field is
      generated. Because of the planet's slow rotation the resulting magnetic field is
      dominated by small-scale components that fluctuate rapidly with time. The dynamo
      field diffuses through the stable conducting region, where rapidly varying parts
      are strongly attenuated by the skin effect, while the slowly varying dipole and
      quadrupole components pass to some degree. The model explains the observed
      structure and strength of Mercury's surface magnetic field and makes predictions
      that are testable with space missions both presently flying and planned.

PMID- 17183320
TI  - Observation of the radiative decay mode of the free neutron.
AB  - The theory of quantum electrodynamics (QED) predicts that beta decay of the
      neutron into a proton, electron and antineutrino should be accompanied by a
      continuous spectrum of soft photons. While this inner bremsstrahlung branch has
      been previously measured in nuclear beta and electron capture decay, it has never
      been observed in free neutron decay. Recently, the photon energy spectrum and
      branching ratio for neutron radiative decay have been calculated using two
      approaches: a standard QED framework and heavy baryon chiral perturbation theory
      (an effective theory of hadrons based on the symmetries of quantum
      chromodynamics). The QED calculation treats the nucleons as point-like, whereas
      the latter approach includes the effect of nucleon structure in a systematic way.
      Here we observe the radiative decay mode of free neutrons, measuring photons in
      coincidence with both the emitted electron and proton. We determined a branching
      ratio of (3.13 +/- 0.34) x 10(-3) (68 per cent level of confidence) in the energy
      region between 15 and 340 keV, where the uncertainty is dominated by systematic
      effects. The value is consistent with the predictions of both theoretical
      approaches; the characteristic energy spectrum of the radiated photons, which
      differs from the uncorrelated background spectrum, is also consistent with the
      calculated spectrum. This result may provide opportunities for more detailed
      investigations of the weak interaction processes involved in neutron beta decay.

PMID- 17183321
TI  - Fortnightly variations in the flow velocity of Rutford Ice Stream, West
      Antarctica.
AB  - Most of the ice lost from the Antarctic ice sheet passes through a few fast
      flowing and highly dynamic ice streams. Quantifying temporal variations in flow
      in these ice streams, and understanding their causes, is a prerequisite for
      estimating the potential contribution of the Antarctic ice sheet to global sea
      level change. Here I show that surface velocities on a major West Antarctic Ice
      Stream, Rutford Ice Stream, vary periodically by about 20 per cent every two
      weeks as a result of tidal forcing. Tidally induced motion on ice streams has
      previously been thought to be limited to diurnal or even shorter-term variations.
      The existence of strong fortnightly variations in flow demonstrates the potential
      pitfalls of using repeated velocity measurements over intervals of days to infer
      long-term change.

PMID- 17183322
TI  - Intrasexual competition and sexual selection in cooperative mammals.
AB  - In most animals, the sex that invests least in its offspring competes more
      intensely for access to the opposite sex and shows greater development of
      secondary sexual characters than the sex that invests most. However, in some
      mammals where females are the primary care-givers, females compete more
      frequently or intensely with each other than males. A possible explanation is
      that, in these species, the resources necessary for successful female
      reproduction are heavily concentrated and intrasexual competition for breeding
      opportunities is more intense among females than among males. Intrasexual
      competition between females is likely to be particularly intense in cooperative
      breeders where a single female monopolizes reproduction in each group. Here, we
      use data from a twelve-year study of wild meerkats (Suricata suricatta), where
      females show high levels of reproductive skew, to show that females gain greater
      benefits from acquiring dominant status than males and traits that increase
      competitive ability exert a stronger influence on their breeding success. Females
      that acquire dominant status also develop a suite of morphological, physiological
      and behavioural characteristics that help them to control other group members.
      Our results show that sex differences in parental investment are not the only
      mechanism capable of generating sex differences in reproductive competition and
      emphasize the extent to which competition for breeding opportunities between
      females can affect the evolution of sex differences and the operation of sexual
      selection.

PMID- 17183323
TI  - Inhibition of Dll4 signalling inhibits tumour growth by deregulating
      angiogenesis.
AB  - Haploinsufficiency of Dll4, a vascular-specific Notch ligand, has shown that it
      is essential for embryonic vascular development and arteriogenesis.
      Mechanistically, it is unclear how the Dll4-mediated Notch pathway contributes to
      complex vascular processes that demand meticulous coordination of multiple
      signalling pathways. Here we show that Dll4-mediated Notch signalling has a
      unique role in regulating endothelial cell proliferation and differentiation.
      Neutralizing Dll4 with a Dll4-selective antibody rendered endothelial cells
      hyperproliferative, and caused defective cell fate specification or
      differentiation both in vitro and in vivo. In addition, blocking Dll4 inhibited
      tumour growth in several tumour models. Remarkably, antibodies against Dll4 and
      antibodies against vascular endothelial growth factor (VEGF) had paradoxically
      distinct effects on tumour vasculature. Our data also indicate that Dll4-mediated
      Notch signalling is crucial during active vascularization, but less important for
      normal vessel maintenance. Furthermore, unlike blocking Notch signalling
      globally, neutralizing Dll4 had no discernable impact on intestinal goblet cell
      differentiation, supporting the idea that Dll4-mediated Notch signalling is
      largely restricted to the vascular compartment. Therefore, targeting Dll4 might
      represent a broadly efficacious and well-tolerated approach for the treatment of
      solid tumours.

PMID- 17183326
TI  - New standard for rabies vaccines?

PMID- 17183327
TI  - 'Hot' new treatment for HIV.

PMID- 17183330
TI  - A closer look: secondary glaucoma more likely.

PMID- 17183333
TI  - Animal Enterprise Terrorism Act becomes law.

PMID- 17183334
TI  - The importance of being 'in charge': a compromise for co-PIs.

PMID- 17183335
TI  - Protocol review: the importance of being 'in charge'.

PMID- 17183336
TI  - The importance of being 'in charge': a word from OLAW and USDA.

PMID- 17183337
TI  - The importance of being 'in charge': increase PI involvement.

PMID- 17183338
TI  - The importance of being 'in charge': the buck stops where?

PMID- 17183339
TI  - Severe runting in a laboratory mouse (Mus musculus).

PMID- 17183341
TI  - Temporary tarsorrhaphy in the rat.
AB  - Temporarily suturing the eyelids together may be necessary in certain studies
      where corneal dryness or ulceration may appear as secondary complications to
      experimental manipulation. This column describes the surgical technique of
      tarsorrhaphy in general, and details its use in the rat.

PMID- 17183342
TI  - Field studies and the IACUC: protocol review, oversight, and occupational health
      and safety considerations.
AB  - Field studies involving animals, like other institutional research endeavors, are
      regulated and evaluated by an IACUC to insure that the protocols employed in
      those studies are consistent with the most humane care and use of animals. Unlike
      many other on-site research projects, however, field studies present unique
      logistical and other challenges to IACUC evaluation. The authors explore many of
      these challenges, including the special protocol considerations and idiosyncratic
      occupational health and safety concerns characteristic of field-study reviews.

PMID- 17183343
TI  - Attempting to reduce regurgitation and reingestion in a captive chimpanzee
      through increased feeding opportunities: a case study.
AB  - Persistent regurgitation and reingestion is an abnormal behavior seen in many
      captive NHPs, particularly gorillas and chimpanzees. Successful reduction of
      regurgitation in captive gorillas has been achieved by providing browse, such as
      branches and leaves, and feeding continuously throughout the day. However, this
      modality has not been tested in chimpanzees. The authors tested these methods in
      a 15-year-old male chimpanzee (Pan troglodytes) with a seven-year history of
      regurgitation and reingestion by alternately providing additional opportunities
      to forage or giving daily browse. The results show that providing browse on a
      daily basis models the feeding behavior of wild chimpanzees and is a successful
      way to reduce regurgitation and reingestion in a chimpanzee unresponsive to
      previous dietary changes.

PMID- 17183344
TI  - Managerial ascent: interview by Owen Young.

PMID- 17183345
TI  - Valsartan treatment reverses erectile dysfunction in diabetic rats.
AB  - In order to investigate the effect of angiotensin receptor blockage (ARB) for the
      treatment on diabetic erectile dysfunction (ED), we used male Sprague-Dawley rats
      injected with 65 mg/kg streptozotocin to induce diabetes mellitus. The diabetic
      rats with ED were selected by hypodermic injection of apomorphine (APO) after 8
      weeks of model setting. All rats were divided into four groups: G1 (normal
      control rats), G2 (diabetic rats treated with normal saline), G3 (diabetic rats
      treated with valsartan) and G4 (diabetic rats treated with spironolactone). After
      treatment with drugs for 8 weeks, the rate of erection for each group was
      evaluated after the injection of APO. The intracavernous pressure (ICP) of each
      rat was then recorded before and after the electrostimulation of the major pelvic
      ganglion. The rates of erection and the ICP after electrostimulation for diabetic
      rats treated with valsartan were significantly higher than that in diabetic rats
      treated with normal saline and spironolactone. The ARB may be an effective
      therapy for diabetics with ED.

PMID- 17183346
TI  - Do vardenafil and tadalafil have advantages over sildenafil in the treatment of
      erectile dysfunction?
AB  - Erectile dysfunction (ED) affects up to 50% of men between the ages of 40 and 70
      years of age. Sildenafil, vardenafil and tadalafil have all been shown to be
      similarly effective in the treatment of men with ED of vary etiologies, to have
      similar adverse effects profiles, and to improve quality-of-life by similar
      amounts. As these phosphodiesterase 5 (PDE5) inhibitors all increase the
      hypotensive effects of nitrates, they are not suitable for use in patients taking
      nitrates for the treatment of ischaemic heart disease. All three inhibitors must
      be used with caution in patients taking alpha(1)-adrenoceptors antagonists for
      benign prostatic hyperplasia. Although nonarteritic anterior ischaemic neuropathy
      has been reported in some users of the PDE5 inhibitors, there is no conclusive
      evidence that PDE5 inhibitors cause this rare effect. Tadalafil has a longer half
      life than sildenafil or vardenafil, and a longer duration of action than
      sildenafil and vardenafil. Most preference studies have shown tadalafil to be
      preferred, but there are serious limitations to some of these studies. One
      approach to treatment is to give each patient a short- and long-acting agent, and
      for individuals to decide their preference.

PMID- 17183347
TI  - Cytotoxic-free treatment designs: time to resistance.

PMID- 17183348
TI  - Bone-marrow-derived cells and cancer--an opportunity for improved therapy.

PMID- 17183349
TI  - Is breast conservation a reasonable option for women with BRCA-associated breast
      cancer?

PMID- 17183350
TI  - Does shorter duration of chemotherapy worsen survival for elderly patients with
      colon cancer?

PMID- 17183351
TI  - Improved survival in metastatic breast cancer following total excision of the
      primary tumor.

PMID- 17183352
TI  - Should young patients with neuroblastoma receive high-dose platinum compounds?

PMID- 17183353
TI  - Quality of life for patients with epithelial ovarian cancer.
AB  - Ovarian cancer is the sixth most common cancer worldwide and the seventh most
      common cause of deaths from cancer in women. Recent annual worldwide figures
      reflect 204,000 new cases of ovarian cancer and 125,000 deaths. Treatment of
      advanced ovarian cancer involves a combination of surgery and chemotherapy, both
      of which may impact a woman's physical, social, and emotional well-being. A
      woman's quality of life (QOL) is affected by disease site, and treatment-specific
      and patient-specific factors, but other common QOL issues include changes in
      physical functioning owing to side effects of treatment, psychological distress
      caused by fear and anxiety of recurrence, sexual dysfunction associated with
      anatomic and physiologic changes of treatment, and for younger women, loss of
      childbearing potential. As new diagnostic and treatment strategies for
      gynecologic malignancies are developed, research efforts should include QOL
      consequences. Further studies are needed to develop strategies for identifying
      women at risk for serious QOL disruption so that effective interventions to
      assist these women can be designed.

PMID- 17183354
TI  - The clinical significance of disseminated tumor cells in breast cancer.
AB  - The presence of tumor cells in the bone marrow of primary breast cancer patients
      at surgery has been shown to be an independent prognostic indicator of relapse.
      Tumor cells have been detected either directly, using immunocytochemical
      staining, or indirectly, using reverse transcription-polymerase chain reaction
      (RT-PCR). Studies have been initiated to determine whether the presence of
      disseminated cells can be monitored during the therapy of patients with primary
      breast cancer, and thus potentially be used to predict relapse before overt
      metastases are detectable. Studies are also ongoing to improve methods of
      detection, such as immunobead enrichment followed by staining and real-time RT
      PCR, and to find alternative markers for the disseminated cells. Studies of
      patients with overt metastases have shown that there is a large tumor load in the
      peripheral blood and that this predicts overall survival. This article reviews
      the published literature on studies carried out in both primary and metastatic
      breast cancer patients, the methodologies and markers used, and improvements in
      detection methodologies that are being investigated including real-time RT-PCR,
      novel markers, enrichment and automated image analysis.

PMID- 17183355
TI  - Therapy insight: the risks and benefits of bisphosphonates for the treatment of
      tumor-induced bone disease.
AB  - Bisphosphonates are a valuable class of drugs with potent anti-resorptive actions
      that make them ideal for skeletal protection in osteoporosis, cancer bone
      metastasis, multiple myeloma, and Paget's disease of bone. It has become
      apparent, however, that these drugs also have the potential to cause a number of
      adverse effects. While these do not limit bisphosphonate use, the incidence of
      these adverse events can be minimized if appropriate care is taken with their
      administration, and by maintaining appropriate surveillance and patient care. We
      review the range of adverse reactions to bisphosphonate therapy with a particular
      emphasis on the recently identified association between long-term bisphosphonate
      treatment and osteonecrosis of the jaw. This is a potentially serious side effect
      seen mostly in patients with multiple myeloma or breast cancer bone metastases
      who receive intravenous bisphosphonate treatment. While the etiology is
      uncertain, a strong association with dental pathology and interventions
      highlights the need for close attention to dental health in this patient group.

PMID- 17183356
TI  - Locally recurrent and metastatic apocrine-gland carcinoma in an elderly man.
AB  - BACKGROUND: A 78-year-old man with a history of untreated hypertension and
      dementia presented with a rapidly growing, painful mass in the left axilla. He
      was a nonsmoker and did not consume alcohol. There was no family history of
      malignancy. The patient had not experienced any constitutional symptoms, such as
      fever, weight loss, night sweats, or loss of appetite. INVESTIGATIONS: Physical
      examination, blood tests, excisional biopsy, studies of tumor morphology and
      immunohistochemistry, CT of the chest and abdomen, and PET scan. DIAGNOSIS:
      Carcinoma of the axillary apocrine gland. MANAGEMENT: Surgical excision, and
      radiation therapy.

PMID- 17183357
TI  - P bodies: at the crossroads of post-transcriptional pathways.
AB  - Post-transcriptional processes have a central role in the regulation of
      eukaryotic gene expression. Although it has been known for a long time that these
      processes are functionally linked, often by the use of common protein factors, it
      has only recently become apparent that many of these processes are also
      physically connected. Indeed, proteins that are involved in mRNA degradation,
      translational repression, mRNA surveillance and RNA-mediated gene silencing,
      together with their mRNA targets, colocalize within discrete cytoplasmic domains
      known as P bodies. The available evidence indicates that P bodies are sites where
      mRNAs that are not being translated accumulate, the information carried by
      associated proteins and regulatory RNAs is integrated, and their fate - either
      translation, silencing or decay - is decided.

PMID- 17183358
TI  - Illuminating the silence: understanding the structure and function of small RNAs.
AB  - RNA interference (RNAi) is triggered by double-stranded RNA helices that have
      been introduced exogenously into cells as small interfering (si)RNAs or that have
      been produced endogenously from small non-coding RNAs known as microRNAs
      (miRNAs). RNAi has become a standard experimental tool and its therapeutic
      potential is being aggressively harnessed. Understanding the structure and
      function of small RNAs, such as siRNAs and miRNAs, that trigger RNAi has shed
      light on the RNAi machinery. In particular, it has highlighted the assembly and
      function of the RNA-induced silencing complex (RISC), and has provided guidelines
      to efficiently silence genes for biological research and therapeutic applications
      of RNAi.

PMID- 17183359
TI  - The WASP-WAVE protein network: connecting the membrane to the cytoskeleton.
AB  - Wiskott-Aldrich syndrome protein (WASP) and WASP-family verprolin-homologous
      protein (WAVE) family proteins are scaffolds that link upstream signals to the
      activation of the ARP2/3 complex, leading to a burst of actin polymerization.
      ARP2/3-complex-mediated actin polymerization is crucial for the reorganization of
      the actin cytoskeleton at the cell cortex for processes such as cell movement,
      vesicular trafficking and pathogen infection. Large families of membrane-binding
      proteins were recently found to interact with WASP and WAVE family proteins,
      therefore providing a new layer of membrane-dependent regulation of actin
      polymerization.

PMID- 17183360
TI  - Integrating cell-signalling pathways with NF-kappaB and IKK function.
AB  - Nuclear factor (NF)-kappaB and inhibitor of NF-kappaB kinase (IKK) proteins
      regulate many physiological processes, including the innate- and adaptive-immune
      responses, cell death and inflammation. Disruption of NF-kappaB or IKK function
      contributes to many human diseases, including cancer. However, the NF-kappaB and
      IKK pathways do not exist in isolation and there are many mechanisms that
      integrate their activity with other cell-signalling networks. This crosstalk
      constitutes a decision-making process that determines the consequences of NF
      kappaB and IKK activation and, ultimately, cell fate.

PMID- 17183361
TI  - Capturing cyclic nucleotides in action: snapshots from crystallographic studies.
AB  - Fifty years ago, cyclic AMP was discovered as a second messenger of hormone
      action, heralding the age of signal transduction. Many cellular processes were
      found to be regulated by cAMP and the related cyclic GMP. Cyclic nucleotides
      function by binding to and activating their effectors - protein kinase A, protein
      kinase G, cyclic-nucleotide-regulated ion channels and the guanine nucleotide
      exchange factor Epac. Recent structural insights have now made it possible to
      propose a general structural mechanism for how cyclic nucleotides regulate these
      proteins.

PMID- 17183362
TI  - Palmitoylation: policing protein stability and traffic.
AB  - Palmitate modifies both peripheral and integral membrane proteins and its
      addition can be permanent or transient, which makes it unique among the lipid
      modifications of proteins. The presence of palmitate on a protein affects how the
      protein interacts with lipids and proteins in a membrane compartment, and the
      reversibility of palmitoylation allows different modes of trafficking between
      membrane compartments. Here, we review recent studies that have provided insights
      into the mechanisms that mediate the functional consequences of this versatile
      modification.

PMID- 17183363
TI  - The chromatoid body: a germ-cell-specific RNA-processing centre.
AB  - The chromatoid body, a unique cloud-like structure of male germ cells, moves
      dynamically in the cytoplasm of haploid spermatids, but its function has remained
      elusive for decades. Recent findings indicate that microRNA and RNA-decay
      pathways converge to the chromatoid body. This highly specialized structure might
      function as an intracellular focal domain that organizes and controls RNA
      processing in male germ cells.

PMID- 17183364
TI  - Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of
      parathyroid hormone-related peptide and E2A-HLF from translocation 17;19.
AB  - Hypercalcemia is relatively rare but clinically important complication in
      childhood leukemic patients. To clarify the clinical characteristics, mechanisms
      of hypercalcemia, response to management for hypercalcemia, incidence of t(17;19)
      and final outcome of childhood acute lymphoblastic leukemia (ALL) accompanied by
      hypercalcemia, clinical data of 22 cases of childhood ALL accompanied by
      hypercalcemia (>12 mg/dl) reported in Japan from 1990 to 2005 were
      retrospectively analyzed. Eleven patients were 10 years and older. Twenty
      patients had low white blood cell count (<20 x 10(9)/l), 15 showed hemoglobin> or
      =8 g/dl and 14 showed platelet count > or =100 x 10(9)/l. Parathyroid hormone
      related peptide (PTHrP)-mediated hypercalcemia was confirmed in 11 of the 16
      patients in whom elevated-serum level or positive immunohistochemistry of PTHrP
      was observed. Hypercalcemia and accompanying renal insufficiency resolved
      quickly, particularly in patients treated with bisphosphonate. t(17;19) or
      add(19)(p13) was detected in five patients among 17 patients in whom karyotypic
      data were available, and the presence of E2A-HLF was confirmed in these five
      patients. All five patients with t(17;19)-ALL relapsed very early. Excluding the
      t(17;19)-ALL patients, the final outcome of ALL accompanied by hypercalcemia was
      similar to that of all childhood ALL patients, indicating that the development of
      hypercalcemia itself is not a poor prognostic factor.

PMID- 17183365
TI  - Control of prostate cell growth: BMP antagonizes androgen mitogenic activity with
      incorporation of MAPK signals in Smad1.
AB  - Alterations in the signaling pathways of bone morphogenetic proteins (BMPs) and
      activation of the ERK/MAP kinase (MAPK) pathway by growth factors have been
      implicated in the development and progression of prostate cancer. Smad1 acts as a
      substrate for MAPKs and also performs a central role in transmitting signals from
      BMPs. We found that BMPs/Smad1 signaling inhibits the growth of androgen
      sensitive prostate cancer cells. Upon the incorporation of ERK/MAPK signals at
      its linker region, Smad1 physically interacts with androgen-activated androgen
      receptor (AR) and suppresses its functions. BMPs induce the function of Smad1 as
      an AR transcriptional corepressor. We demonstrated in vivo that Smad1 signaling
      is low in androgen-regulated growth of prostate cancer, is activated after
      castration, and also is decreased in hormone-independent tumors. The activation
      status of ERK/MAPK parallels Smad1 in the progression of prostate cancer; thus,
      our findings indicate a molecular basis for the integration of signals of MAPK
      and Smad1 in the progression and androgen regulation of prostate cancer.

PMID- 17183366
TI  - A nucleo-cytoplasmic SR protein functions in viral IRES-mediated translation
      initiation.
AB  - A significant number of viral and cellular mRNAs utilize cap-independent
      translation, employing mechanisms distinct from those of canonical translation
      initiation. Cap-independent translation requires noncanonical, cellular RNA
      binding proteins; however, the roles of such proteins in ribosome recruitment and
      translation initiation are not fully understood. This work demonstrates that a
      nucleo-cytoplasmic SR protein, SRp20, functions in internal ribosome entry site
      (IRES)-mediated translation of a viral RNA. We found that SRp20 interacts with
      the cellular RNA-binding protein, PCBP2, a protein that binds to IRES sequences
      within the genomic RNAs of certain picornaviruses and is required for viral
      translation. We utilized in vitro translation in HeLa cell extracts depleted of
      SRp20 to demonstrate that SRp20 is required for poliovirus translation
      initiation. Targeting SRp20 in HeLa cells with short interfering RNAs resulted in
      inhibition of SRp20 protein expression and a corresponding decrease in poliovirus
      translation. Our data have identified a previously unknown function of an SR
      protein (i.e., the stimulation of IRES-mediated translation), further documenting
      the multifunctional nature of this important class of cellular RNA-binding
      proteins.

PMID- 17183367
TI  - COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin
      containing ubiquitin ligase.
AB  - NF-kappaB is a pleiotropic transcription factor involved in multiple processes,
      including inflammation and oncogenesis. We have previously reported that COMMD1
      represses kappaB-dependent transcription by negatively regulating NF-kappaB
      chromatin interactions. Recently, ubiquitination of NF-kappaB subunits has been
      similarly implicated in the control of NF-kappaB recruitment to chromatin. We
      report here that COMMD1 accelerates the ubiquitination and degradation of NF
      kappaB subunits through its interaction with a multimeric ubiquitin ligase
      containing Elongins B and C, Cul2 and SOCS1 (ECS(SOCS1)). COMMD1-deficient cells
      demonstrate stabilization of RelA, greater nuclear accumulation of RelA after TNF
      stimulation, de-repression of several kappaB-responsive genes, and enhanced NF
      kappaB-mediated cellular responses. COMMD1 binds to Cul2 in a stimulus-dependent
      manner and serves to facilitate substrate binding to the ligase by stabilizing
      the interaction between SOCS1 and RelA. Our data uncover that ubiquitination and
      degradation of NF-kappaB subunits by this COMMD1-containing ubiquitin ligase is a
      novel and critical mechanism of regulation of NF-kappaB-mediated transcription.

PMID- 17183368
TI  - Insulin delays the progression of Drosophila cells through G2/M by activating the
      dTOR/dRaptor complex.
AB  - In Drosophila and mammals, insulin signalling can increase growth, progression
      through G1/S, cell size and tissue size. Here, we analyse the way insulin affects
      cell size and cell-cycle progression in two haemocyte-derived Drosophila cell
      lines. Surprisingly, we find that although insulin increases cell size, it slows
      the rate at which these cells increase in number. By using BrdU pulse-chase to
      label S-phase cells and follow their progression through the cell cycle, we show
      that insulin delays progression through G2/M, thereby slowing cell division. The
      ability of insulin to slow progression through G2/M is independent of its ability
      to stimulate progression through G1/S, so is not a consequence of feedback by the
      cell-cycle machinery to maintain cell-cycle length. Insulin's effects on
      progression through G2/M are mediated by dTOR/dRaptor signalling. Partially
      inhibiting dTOR/dRaptor signalling by dsRNAi or mild rapamycin treatment can
      increase cell number in cultured haemocytes and the Drosophila wing,
      respectively. Thus, insulin signalling can influence cell number depending on a
      balance between its ability to accelerate progression through G1/S and delay
      progression through G2/M.

PMID- 17183369
TI  - The ubiquitin-proteasome system regulates membrane fusion of yeast vacuoles.
AB  - Ubiquitination is known to regulate early stages of intracellular vesicular
      transport, without proteasomal involvement. We now show that, in yeast,
      ubiquitination regulates a late-stage, membrane fusion, with proteasomal
      involvement. A known proteasome mutant had a vacuolar fragmentation phenotype in
      vivo often associated with vacuolar membrane fusion defects, suggesting a
      proteasomal role in fusion. Inhibiting vacuolar proteasomes interfered with
      membrane fusion in vitro, showing that fusion cannot occur without proteasomal
      degradation. If so, one would expect to find ubiquitinated proteins on vacuolar
      membranes. We found a small number of these, identified the most prevalent one as
      Ypt7 and mapped its two major ubiquitination sites. Ubiquitinated Ypt7 was linked
      to the degradation event that is necessary for fusion: vacuolar Ypt7 and vacuolar
      proteasomes were interdependent, ubiquitinated Ypt7 became a proteasomal
      substrate during fusion, and proteasome inhibitors reduced fusion to greater
      degree when we decreased Ypt7 ubiquitination. The strongest model holds that
      fusion cannot proceed without proteasomal degradation of ubiquitinated Ypt7. As
      Ypt7 is one of many Rab GTPases, ubiquitin-proteasome regulation may be involved
      in membrane fusion elsewhere.

PMID- 17183372
TI  - Achieving balance.

PMID- 17183373
TI  - Green up your act.

PMID- 17183370
TI  - Foxo and Fos regulate the decision between cell death and survival in response to
      UV irradiation.
AB  - Cells damaged by environmental insults have to be repaired or eliminated to
      ensure tissue homeostasis in metazoans. Recent studies suggest that the balance
      between cell survival signals and pro-apoptotic stimuli controls the decision
      between cell repair and death. How these competing signals are integrated and
      interpreted to achieve accurate control over cell fate in vivo is incompletely
      understood. Here, we show that the Forkhead Box O transcription factor Foxo and
      the AP-1 transcription factor DFos are required downstream of Jun-N-terminal
      kinase signaling for the apoptotic response to UV-induced DNA damage in the
      developing Drosophila retina. Both transcription factors regulate the pro
      apoptotic gene hid. Our results indicate that UV-induced apoptosis is repressed
      by receptor tyrosine kinase-mediated inactivation of Foxo. These data suggest
      that integrating stress and survival signals through Foxo drives the decision
      between cell death and repair of damaged cells in vivo.

PMID- 17183374
TI  - Time to move on.

PMID- 17183375
TI  - Left out to dry.

PMID- 17183384
TI  - Effective infection control to prevent exposure to HIV.

PMID- 17183386
TI  - Challenges to teaching posterior composites in the United Kingdom and Ireland.
AB  - Recent surveys from general dental practice have found increased placement of
      direct composite resin restorations in occlusal (Class I) and occlusoproximal
      (Class II) cavities in permanent teeth by general dental practitioners. This has
      been matched, and possibly driven, at least in part, by the development of new
      composite resin materials and bonding technologies. Recent studies by the authors
      have found an increase in the teaching of Class I and Class II composite resin
      restorations in the UK, Ireland, the US, and Canada. The increased teaching in
      the UK and Ireland, however, was not as great as in North America, and several
      worrying trends were observed. The aim of this paper is to discuss these trends
      and related factors considered important to the necessary further development of
      the teaching of Class I and Class II direct composite resin restorations, let
      alone modern operative dentistry in general, in the UK and Ireland.

PMID- 17183387
TI  - The role of orthodontics in implant dentistry.
AB  - Orthodontic treatment of partially edentulous patients is difficult, especially
      if a significant number of teeth are missing. With loss of teeth, adjacent or
      opposing teeth usually tip, drift or over-erupt leaving spaces that are not
      optimal for replacement of missing teeth. Orthodontic correction of these spatial
      relationships will aid prosthetic replacement of the missing teeth, function,
      hygiene and aesthetics. Orthodontists rely on teeth to provide the anchorage to
      correct malocclusions. With patients with an intact dentition dental anchorage is
      usually adequate to facilitate tooth movement. In some partially edentulous
      patients however, insufficient anchorage may present to correct the malocclusion.
      In these patients implants can provide additional anchorage. At times,
      osseointegrated implants can also be used to support restorations after
      completion of orthodontic therapy if treatment planning is precise. The use of
      implants for orthodontic anchorage requires an interdisciplinary approach and
      precise planning to achieve optimal results.

PMID- 17183393
TI  - Dental screening in schools: the views of parents, teachers and school nurses.
AB  - OBJECTIVES: To obtain insight into the views of relevant 'stakeholders' (parents,
      teachers and school nurses) in dental screening in schools. METHODS: Eight
      schools in Chester and Ellesmere Port in the UK formed the setting of this study.
      A teacher from each school participated in one-to-one interviews, and focus
      groups for parents were carried out in each school. A focus group for school
      nurses working in the locality was also held. The same trained researcher
      undertook the interviews and focus groups; all interviews and focus groups were
      tape recorded, transcribed verbatim and thematically analysed independently by
      two trained individuals. RESULTS: Teachers, school nurses and parents all
      perceived the process of negative consent and the current dental examination as
      acceptable. The follow up procedure for identification of screened positive
      children was seen as inadequate. There was a strong feeling within each group
      that parents were ultimately responsible for their children's oral health and
      that state institutions had a limited role in ensuring children attended and
      received dental treatment. CONCLUSIONS: All of the groups considered it was
      primarily the responsibility of parents to take screened positive children to see
      a dentist. The NHS has limited influence on this process. This fact represents a
      significant challenge to improving the effectiveness of school dental screening.

PMID- 17183394
TI  - Evaluation of vocational training of dentists in three different regions.
AB  - OBJECTIVE: To carry out an in depth evaluation of the vocational training year.
      DESIGN: Qualitative structured focus groups and interviews. SETTING: Three
      regional vocational training schemes in the south of England. METHODS: Each
      scheme provided a group of six vocational dental practitioners (VDPs) who met
      with researchers at three points in the training year. Additionally one of the
      researchers interviewed advisers and trainers. RESULTS: and recommendations
      Possible improvements were identified in the appointment process, induction,
      tutorials, assessment of clinical knowledge, technical skill, social and
      communication skills and development of the skills of reflective practice.
      CONCLUSIONS: The vocational training year is a very good learning experience,
      which could be further enhanced to make it excellent.

PMID- 17183395
TI  - Pierre Fauchard: the 'father of modern dentistry'.
AB  - The development of the modern practice of dentistry can be traced to the work and
      life of Pierre Fauchard, a French dentist who worked in the first half of the
      eighteenth century. Fauchard was an exceptionally gifted and talented
      practitioner, who introduced many innovations to dentistry. In a significant
      break with the tradition of the time, he shared his knowledge and techniques with
      colleagues, and published these in the first comprehensive dental textbook. This
      paper reviews his life and contribution to modern dentistry.

PMID- 17183410
TI  - The implications of the Human Tissue Act 2004 for dentistry.
AB  - Partly as a consequence of the inquiries into the events at the Bristol Royal
      Infirmary and the Royal Liverpool Children's Hospital (Alder Hey), the Government
      recently enacted the Human Tissue Act 2004. The main provisions of the Act came
      into force on 1 September 2006 and have potential implications for dentists.

PMID- 17183411
TI  - Organizational Culture and Climate and Mental Health Provider Attitudes Toward
      Evidence-Based Practice.
AB  - Mental health provider attitudes toward adopting evidence-based practice (EBP)
      are associated with organizational context and provider individual differences.
      Organizational culture and climate are contextual factors that can affect staff
      acceptance of innovation. This study examined the association of organizational
      culture and climate with attitudes toward adopting EBP. Participants were 301
      public sector mental health service providers from 49 programs providing mental
      health services for youths and families. Correlation analyses and multilevel
      hierarchical regressions, controlling for effects of provider characteristics,
      showed that constructive culture was associated with more positive attitudes
      toward adoption of EBP and poor organizational climates with perceived divergence
      of usual practice and EBP. Behavioral health organizations may benefit from
      consideration of how culture and climate affect staff attitudes toward change in
      practice.

PMID- 17183412
TI  - The Presentation of Body Dysmorphic Disorder in Medical Settings.
AB  - Body dysmorphic disorder (BDD) is a relatively common psychiatric illness that
      often presents to mental health professionals as well as nonpsychiatric
      physicians. However, BDD usually goes unrecognized and undiagnosed in clinical
      settings. It is important to recognize and accurately diagnose BDD because this
      often secret illness may be debilitating. Patients with BDD typically have
      markedly impaired functioning, notably poor quality of life, and a high rate of
      suicidal ideation and suicide attempts. Thus, it is important to screen patients
      for BDD and avoid misdiagnosing it as another illness. Nonpsychiatric treatments
      (eg, dermatologic, surgical), which most patients seek and receive, appear
      ineffective for BDD and can be risky for physicians to provide. This article
      provides a clinically focused overview of BDD, including its symptoms, morbidity,
      case examples, nonpsychiatric (ie, cosmetic) treatment, diagnostic "do's" and
      "don'ts," and suggestions for how to persuade patients to accept appropriate
      psychiatric care.

PMID- 17183413
TI  - Femtosecond broadband stimulated Raman spectroscopy: Apparatus and methods.
AB  - The laser, detection system, and methods that enable femtosecond broadband
      stimulated Raman spectroscopy (FSRS) are presented in detail. FSRS is a unique
      tool for obtaining high time resolution (<100 fs) vibrational spectra with an
      instrument response limited frequency resolution of <10 cm(-1). A
      titanium:Sapphire-based laser system produces the three different pulses needed
      for FSRS: (1) A femtosecond visible actinic pump that initiates the
      photochemistry, (2) a narrow bandwidth picosecond Raman pump that provides the
      energy reservoir for amplification of the probe, and (3) a femtosecond continuum
      probe that is amplified at Raman resonances shifted from the Raman pump. The
      dependence of the stimulated Raman signal on experimental parameters is explored,
      demonstrating the expected exponential increase in Raman intensity with
      concentration, pathlength, and Raman pump power. Raman spectra collected under
      different electronic resonance conditions using highly fluorescent samples
      highlight the fluorescence rejection capabilities of FSRS. Data are also
      presented illustrating our ability: (i) To obtain spectra when there is a large
      transient absorption change by using a shifted excitation difference technique
      and (ii) to obtain high time resolution vibrational spectra of transient
      electronic states.

PMID- 17183415
TI  - Hospital mortality rates of infants with birth weight less than or equal to 1,500
      g in the northeast of Brazil.
AB  - OBJECTIVE: To obtain information on the hospital mortality of infants born in
      Fortaleza with birth weights less than or equal to 1,500 g, and to compare it
      with data from the Vermont Oxford Network, a center of excellence for neonatal
      care. METHODS: Prospective cohort study, enrolling all infants with birth weight
      less than or equal to 1,500 g born in Fortaleza between March 1, 2002 and
      February 28, 2003 from all the hospitals and maternity units with neonatal
      intensive care units. Infants were followed from birth until hospital discharge
      or hospital death, using the Vermont Oxford Network questionnaire. RESULTS: A
      total of 774 newborn infants were analyzed. The neonatal mortality coefficient
      was 477 per thousand, and the postneonatal mortality coefficient was 35 per
      thousand, taking the hospital mortality coefficient to 512 per thousand. The
      coefficient of early neonatal mortality was 335 per thousand, and the coefficient
      of late neonatal mortality was 142 per thousand. Mortality coefficients were
      higher in Fortaleza for all weight ranges than on the Vermont Oxford Network and
      were also, with the exception of the less than or equal to 600 g weight range,
      higher than in Montevideo. CONCLUSIONS: The results demonstrate high rates of
      hospital mortality among very low birth weight infants, with a greater
      concentration during the first week of life, suggesting that not only the care
      provided at the neonatal intensive care units is deficient, but also that
      prenatal and delivery-room care is inadequate.

PMID- 17183414
TI  - Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and
      Therapeutic Implications.
AB  - Leptin and adiponectin represent two newly discovered adipose tissue derived
      hormones with important roles in energy homeostasis and insulin resistance. Their
      interrelations with the manifestations of the HIV associated metabolic syndrome
      and specific somatomorphic changes i.e. fat redistribution is reviewed. A
      synopsis of published studies is presented and the potential role of leptin and
      adiponectin is discussed. We have described an association of the HIV metabolic
      syndrome with a state of reduced insulin sensitivity due to adiponectin
      deficiency. The metabolic syndrome is also accompanied by leptin deficiency in
      lipoatrophic subjects and possibly by a leptin resistance state in
      lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner
      similar to other leptin deficiency states may assist in the future management of
      such patients.

PMID- 17183417
TI  - The MNA (Mini Nutritional Assessment). Proceedings of an IANA (International
      Academy on Nutrition and Aging) workshop. May 2-3, 2006. Chicago, Illinois, USA.

PMID- 17183416
TI  - Metabolic syndrome and risk factors for cardiovascular disease in obese children:
      the relationship with insulin resistance (HOMA-IR).
AB  - OBJECTIVE: To identify the prevalence of metabolic syndrome and risk factors for
      the development of cardiovascular diseases and to investigate their relationship
      with insulin resistance. METHODS: This was a cross-sectional study of 52 obese
      children. The sample was chosen at random after the body mass index [weight
      (kg)/stature (m)(2)] of 1,550 schoolchildren had been calculated. Children were
      defined as obese when their BMI was above the 95th percentile of the Centers for
      Disease Control and Prevention classification. Blood samples were taken after
      fasting and glycemia, high-density lipoproteins, triglycerides and insulin were
      all assayed. Body fat was evaluated using dual energy X-ray absorptiometry.
      Arterial blood pressure and insulin resistance were also measured. Metabolic
      syndrome was defined according to National Cholesterol Education Program
      criteria, with cutoff points adjusted for the age of the sample. RESULTS:
      Metabolic syndrome was detected in 17.3% of the children investigated. Insulin
      resistance was significantly different for females (3.8-/+2.2; 95%CI 2.9-4.8) and
      males (2.6-/+1.3; 95%CI 2.1-3.1); p = 0.016. Around 44.2% of the sample exhibited
      at least two risk factors, and 15% exhibited arterial hypertension.
      Hypertriglyceridemia was observed in 50 and 70.8% of boys and girls,
      respectively. Lower than desirable high-density lipoprotein levels were only
      observed among the girls. CONCLUSIONS: Obese children exhibited a high prevalence
      of metabolic syndrome. The children with greater insulin resistance exhibited
      more risk factors. In the light of these findings intervention measures are
      necessary in order to prevent excessive weight gain during childhood.

PMID- 17183418
TI  - Overview of the MNA--Its history and challenges.
AB  - The Mini Nutritional Assessment (MNA) is a simple tool, useful in clinical
      practice to measure nutritional status in elderly persons. From its validation in
      1994, the MNA has been used in hundreds of studies and translated into more then
      20 languages. It is a well-validated tool, with high sensitivity, specificity,
      and reliability. An MNA score > or = 24 identifies patients with a good
      nutritional status. Scores between 17 and 23.5 identify patients at risk for
      malnutrition. These patients have not yet started to lose weight and do not show
      low plasma albumin levels but have lower protein-calorie intakes than
      recommended. For them, a multidisciplinary geriatric intervention is needed,
      which takes into account all aspects that might interfere with proper
      alimentation and, when necessary, proposes therapeutic interventions for diet or
      supplementation. If the MNA score is less than 17, the patient has protein
      calorie malnutrition. It is important at this stage to quantify the severity of
      the malnutrition (by measuring biochemical parameters like plasma albumin or
      prealbumin levels, establishing a 3- day record of food intake, and measuring
      anthropometric features like weight, BMI, arm circumference and skin folds).
      Nutritional intervention is clearly needed and should be based on achievable
      objectives established after a detailed comprehensive geriatric assessment. The
      MNA has been shown to be useful for nutritional intervention follow-up as well.
      The MNA can help clinicians design an intervention by noting where the patient
      loses points when performing the MNA. Moreover, when a nutritional intervention
      is successful, the MNA score increases. The MNA is recommended by many national
      and international clinical and scientific organizations. It can be used by a
      variety of professionals, including physicians, dietitians, nurses or research
      assistants. A short screening version (MNA-SF) has been developed, which, if
      positive, indicates the need to complete the full MNA. It takes less than 4
      minutes to administer the MNA-SF and between 10 and 15 minutes for the full MNA.

PMID- 17183419
TI  - The Mini Nutritional Assessment (MNA) review of the literature--What does it tell
      us?
AB  - To review the literature on the MNA to Spring 2006, we searched MEDLINE, Web of
      Science and Scopus, and did a manual search in J Nutr Health Aging, Clin Nutr,
      Eur J Clin Nutr and free online available publications. VALIDATION AND VALIDITY:
      The MNA was validated against two principal criteria, clinical status and
      comprehensive nutrition assessment using principal component and discriminant
      analysis. The MNA shortform (MNA-SF) was developed and validated to allow a 2
      step screening process. The MNA and MNA-SF are sensitive, specific, and accurate
      in identifying nutrition risk. NUTRITIONAL SCREENING: The prevalence of
      malnutrition in community-dwelling elderly (21 studies, n = 14149 elderly) is 2
      +/- 0.1% (mean +/- SE, range 0- 8%) and risk of malnutrition is 24 +/- 0.4%
      (range 8-76%). A similar pattern is seen in out-patient and home care elderly (25
      studies, n = 3119 elderly) with prevalence of undernutrition 9 +/- 0.5% (mean +/-
      SE, range 0-30%) and risk of malnutrition 45 +/- 0.9% (range 8-65%). A high
      prevalence of undernutrition has been reported in hospitalized and
      institutionalized elderly patients: prevalence of malnutrition is 23 +/- 0.5%
      (mean +/- SE, range 1- 74%) in hospitals (35 studies, n = 8596) and 21 +/- 0.5%
      (mean +/- SE, range 5-71%) in institutions (32 studies, n = 6821 elderly). An
      even higher prevalence of risk of malnutrition was observed in the same
      populations, with 46 +/- 0.5% (range 8-63%) and 51 +/- 0.6% (range 27-70%),
      respectively. In cognitively impaired elderly subjects (10 studies, n = 2051
      elderly subjects), detection using the MNA, prevalence of malnutrition was 15 +/-
      0.8% (mean +/- SE, range 0-62%), and 44 +/- 1.1% (range 19-87%) of risk of
      malnutrition. CHARACTERISTICS: The large variability is due to differences in
      level of dependence and health status among the elderly. In hospital settings, a
      low MNA score is associated with an increase in mortality, prolonged length of
      stay and greater likelihood of discharge to nursing homes. Malnutrition is
      associated with functional and cognitive impairment and difficulties eating. The
      MNA(R) detects risk of malnutrition before severe change in weight or serum
      proteins occurs. NUTRITIONAL INTERVENTION: Intervention studies demonstrate that
      timely intervention can stop weight loss in elderly at risk of malnutrition or
      undernourished and is associated with improvements in MNA scores. The MNA can
      also be used as a follow up assessment tool. CONCLUSION: The MNA is a screening
      and assessment tool with a reliable scale and clearly defined thresholds, usable
      by health care professionals. It should be included in the geriatric assessment
      and is proposed in the minimum data set for nutritional interventions.

PMID- 17183420
TI  - Nutritional screening tools--How does the MNA compare? Proceedings of the session
      held in Chicago May 2-3, 2006 (15 Years of Mini Nutritional Assessment).
AB  - Malnutrition occurs frequently in the elderly and is correlated with decreased
      functionality and thereby quality of life, as well as increased morbidity and
      mortality. This holds true for elderly people living in the community, patients
      in acute-care hospitals, as well as residents in long-term care facilities. To
      diagnose malnutrition, it is crucial to have sensitive, easy-to-use and specific
      tools at hand. The focus of this article is to compare strengths and weaknesses
      of the most commonly used assessment tools for malnutrition in the elderly,
      Malnutrition Universal Screening Tool (MUST), Mini Nutrition Assessment (MNA),
      Subjective Global Assessment (SGA), and Nutrition Risk Screening (NRS 2002). In
      conclusion, 15 years after its introduction, the Mini Nutritional Assessment
      (MNA), which was especially developed for elderly people, remains the gold
      standard for ambulatory living elderly and those living in long-term care
      facilities, whereas the NRS 2002 has especially good potential in the acute-care
      setting, as it was developed specifically for hospitalized patients who need
      nutritional support.

PMID- 17183421
TI  - Oral and nutritional status--Is the MNA a useful tool for dental clinics.
AB  - OBJECTIVES: To determine the oral status of elderly residents in nursing homes
      (NH) and long term care wards (LT) and to describe associations between oral
      status and nutritional status among institutionalized elderly residents. DESIGN:
      Descriptive, cross-sectional study. SETTING: All elderly residents in all NH and
      LT in Helsinki, the capital of Finland. PARTICIPANTS: The study included 2036 out
      of 2424 (84 %) eligible subjects in NH, 1052 out of 1444 (73%) eligible subjects
      in LT, and all wards in NH (N = 92) and LT (N = 53). MEASUREMENTS: A structured
      questionnaire, oral examination, and Mini Nutritional Assessment (MNA) were
      completed by ward nurses for all participating residents. The structured
      questionnaire included information on oral status and oral health problems,
      demographic characteristics, functional status, diseases and medication. One
      questionnaire for each ward was used to evaluate the daily ward routines related
      to nutritional care and meal management. RESULTS: 11 % of the NH residents and 3
      % of LH patients were well nourished. Of NH residents 60 % were at risk of
      malnutrition and 29 % were malnourished. The respective figures for LT patients
      were 40 % and 57 %. Nutritional status was significantly associated with oral
      status and with the number of oral health problems. Those with mixed dentition or
      complete dentures tended to have better nutritional status than those totally
      edentulous without prosthesis. Malnutrition increased consistently with the
      increasing number of oral health problems (including chewing problems, swallowing
      difficulties, pain in mouth and xerostomia). CONCLUSION: In the population of
      institutionalized frail elderly, malnutrition was related to both poor oral
      status and oral health problems.

PMID- 17183422
TI  - Usefulness of the MNA in the long-term and acute-care settings within the United
      States.
AB  - The Mini Nutritional Assessment (MNA) is a tool that was developed for use with
      elders to provide rapid assessment of nutritional risk. Although this screening
      tool has been validated and frequently used in longterm and acute-care settings
      in Europe, the MNA has not been used extensively within the United States. The
      MNA may need to be validated for use within U.S. nursing and acute-care
      facilities because validity may be affected by the acuity of illness, the use of
      aggressive nutrition support, which makes the scoring of the MNA difficult, and
      the age of patients admitted for care (acute care). Additionally, in most long
      term care settings, a specific screening tool (Minimum Data Set) is already
      required to assess resident function including nutritional risk. The MNA may be
      more useful in an assisted living facility, where nutrition screening and
      assessment tools are not currently in place, yet maintenance of functional status
      is important to prevent transfer to a nursing facility.

PMID- 17183423
TI  - Obesity among older persons: Screening for risk of adverse outcomes.
AB  - A research overview is presented that highlights the growing prevalence of
      obesity among older persons and the associated risks for medical co-morbidity,
      healthcare resource use, functional decline and homebound status. Findings reveal
      that even for obese individuals poor diet quality and micronutrient deficiencies
      are relatively common concerns. Currently available nutrition risk screening
      instruments lack validity for overweight / obese older persons. Development and
      preliminary testing of a new Nutrition Health Outcomes Questionnaire (NHOQ) for
      this application are presented.

PMID- 17183424
TI  - Is the MNA valid in different populations and across practice settings?
AB  - OBJECTIVE: The MNA is a successful screening tool in geriatric medicine, but this
      success is in Europe or countries with Western health care practice settings. The
      MNA is not directly applicable in many ethnic groups or countries or those with
      non-Western cultural and dietary habits or health care systems. There is an
      increased prevalence of type 2 diabetes, the metabolic syndrome and obesity among
      the elderly; however, the MNA does not include questions or measures related to
      these or other important health conditions affected by nutritional status. This
      paper addresses the relevance of anthropometry and the impact of different
      clinical practice settings on the MNA and discusses the development of the
      Chinese Nutritional Screen (CNS) in China. CONCLUSIONS: If the MNA is to continue
      to be successful among groups of elderly around the world, then the MNA, CNS or
      similar instruments should be as country or culturally and ethnically specific as
      possible. The development of the CNS maintained the underlying assumptions and
      concept of the MNA but modified them for a country with diverse food and cultural
      habits and health care settings.

PMID- 17183425
TI  - Clinical characteristics and risk factors of delirium in demented and not
      demented elderly medical inpatients.
AB  - OBJECTIVES: to evaluate the differences in clinical characteristics and risk
      factors of delirium in elderly medical inpatients according to the presence or
      not of dementia. DESIGN: cross-sectional, observational study. SETTING: acute
      medical care unit (ACU) of a general hospital. PARTICIPANTS: 330 patients aged 65
      and older consecutively admitted on a 24-week period. MEASUREMENTS: Functional
      status, cognitive abilities, severity of acute illness (Acute Physiology, Age and
      Chronic Health Evaluation (APACHE II) score), Confusion Assessment Method (CAM),
      Delirium Rating Scale (DRS) and One Day Fluctuation Scale (ODFS). RESULTS:
      patients with delirium represent 19.1% of the sample, 41.0% of which had also
      dementia. Hyperactive form of delirium was 41.0%; hypoactive 11.0% and mixed
      48.0%. In non demented patients, the delirious patients showed higher APACHE II
      score, more severe functional decline, poorer cognitive status respect to not
      delirious. In demented patients no differences were found in APACHE II score and
      cognitive status among delirious and not delirious subjects. In this group,
      functional decline (p = .012), acute infection (p = .007), psychotropic drugs use
      (p = .028) and severe hypoalbuminemia (p = .036) represented risk factors for the
      onset of delirium. Demented patients had higher perceptual disturbances (p =
      .040) and less severe delusions (p = .001), while total DRS score do not differs
      in the two groups. According to ODFS, delirium episode was more fluctuating in
      patients with dementia. CONCLUSION: clinical characteristics and risk factors of
      delirium are different in demented and not demented elderly inpatients. Patients
      with dementia are vulnerable to delirium at lower levels of medical acuity than
      non-demented patients.

PMID- 17183426
TI  - S-adenosyl methionine: A connection between nutritional and genetic risk factors
      for neurodegeneration in Alzheimer's disease.
AB  - Clinical manifestation of Alzheimer's disease may depend upon interaction among
      its risk factors. Apolipoprotein E-deficient mice undergo oxidative damage and
      cognitive impairment when deprived of folate. We demonstrate herein that these
      mice were depleted in the methyl donor S-adenosyl methionine (SAM), which
      inhibited glutathione S-transferase, since this enzyme requires methylation of
      oxidative species prior to glutathione-dependent reduction. Dietary
      supplementation with SAM alleviated neuropathology. Since SAM deficiency promotes
      presenilin-1 overexpression, which increases gamma-secretase expression and Abeta
      generation, these findings directly link nutritional deficiency and genetic risk
      factors, and support supplementation with SAM for Alzheimer's therapy.

PMID- 17183427
TI  - The value of clinical characteristics from a standard questionnaire to
      discriminate cardiac from neurological syncope in the elderly.
AB  - OBJECTIVES: To identify signs and symptoms to differentiate cardiac from
      neurological syncope in patients over 70 using a standardized questionnaire.
      DESIGN: Prospective cohort study. SETTING: Five short-stay units in a French
      university hospital. PARTICIPANTS: One hundred thirty-one in-patients with
      syncope aged 70 and older. MEASUREMENTS: Patients were interviewed about the
      signs and symptoms that had been present before, during or after syncope. When
      possible, a witness who had been present during syncope was also interviewed to
      compare theirs and the patients' answers. The sensitivity and specificity of 35
      questions were calculated among 3 groups defined according to the cause of
      syncope: cardiac (n = 58), neurological (n = 31) and syncope of unknown origin (n
      = 42). Statistical analyses were performed to determine discriminating signs and
      symptoms among the causes and crude agreement was calculated for answers from
      patients and witnesses. RESULTS: Only 8 and 3 of 35 questions had a sensitivity
      of at least 0.5 for cardiac and neurological causes respectively. A feeling of
      impending syncope, thoracic oppression, recall of events preceding syncope and a
      history of arrhythmia were independently and significantly discriminant among
      groups. Recall of events preceding syncope (Odds Ratio (OR) = 7.5; 95% confidence
      interval (CI) = 2.2-25.3) and a personal history of arrhythmia (OR = 4.8; 95% CI
      = 1.6-14.2) were discriminant between cardiac and neurological causes suggesting
      mostly a cardiac cause. Agreement between patients and witnesses was only found
      for questions on the patient's medical history or the circumstances surrounding
      the onset of syncope. CONCLUSIONS: Recall of events preceding syncope and a
      history of arrhythmia are strongly suggestive of a cardiac rather than a
      neurological cause of syncope. Interviews of witnesses are not helpful in
      suggesting a cause for syncope.

PMID- 17183428
TI  - Meals-on-wheels improves energy and nutrient intake in a frail free-living
      elderly population.
AB  - BACKGROUND: With the increasing life expectancy and associated health care cost
      in the elderly population, it is fundamental to study and improve interventions
      that help older persons to have a better and healthier life in their home for a
      longer period. OBJECTIVES: Evaluate the effect of Meals-on-Wheels (MOW) on
      dietary intakes of frail elderly. DESIGN: An untreated control group quasi
      experimental design with pretest and post-test was used to compare users (n = 20)
      and non-users (n = 31) of MOW. Descriptive and dietary data were compared at
      pretest and 8 weeks later. Analysis of Covariance (ANCOVA) was used to control
      for initial differences between groups. RESULTS: Both groups were similar at
      pretest except for weight (p = 0.028) and weekly number of meals eaten outside
      the home (p = 0.008). In both groups, dietary intakes at pretest were below
      Estimated Average Requirements (EAR) for the same nutrients. At post-test, intake
      of most nutrients increased in the Experimental group in comparison with the
      Control group. After controlling with the ANCOVA model, increases were
      significant for energy (p = 0.050), protein (p = 0.030), lipid (p = 0.034) and
      thiamin (p = 0.035). Provision of MOW did not permit to achieve a low risk of
      nutrient inadequacy in the Experimental group. CONCLUSIONS: MOW programs improve
      dietary intakes of recipients. However, a more intensive intervention is needed
      to prevent nutrient deficiencies in this group.

PMID- 17183429
TI  - Early lymphocyte development in bone marrow and thymus.
AB  - Haematopoietic stem cells (HSCs), a very rare cell type in the bone marrow, are
      responsible for the life-long production of all cells of the blood including T
      and B cells. Until recently, it was thought that the differentiation of HSCs into
      the various haematopoietic cells was rather hierarchical in that differentiation
      along a given lineage was associated with a progressive loss of potential to give
      rise to other blood cell lineages. The recent development of very sensitive and
      quantitative in vitro assays, together with the identification of new progenitor
      subpopulations, has challenged this idea. Thus, lymphocyte progenitors can be
      shown to keep their developmental potential to give rise to myeloid, dendritic
      and NK cells until just prior to their final commitment stage. Here we review
      these new findings and concepts.

PMID- 17183430
TI  - Tolerance to celecoxib in patients with a history of adverse reactions to
      nonsteroidal anti-inflammatory drugs.
AB  - BACKGROUND: Adverse reactions to nonsteroidal antiinflammatory drugs (NSAIDs) are
      frequently reported, particularly among asthmatic patients. To date, there is no
      causal treatment available apart from tolerance induction. Therefore, the search
      for safe alternative drugs is of pivotal importance in clinical practice.
      OBJECTIVE: The aim of our prospective study was to investigate the tolerance to
      celecoxib, a selective cyclooxygenase-2 inhibitor, in a large group of patients
      with positive case history of NSAID intolerance in comparison to paracetamol and
      nimesulide. METHODS: 106 NSAID-sensitive patients, 46 (43.4%) of whom had
      experienced reactions only to one NSAID (single hypersensitivity), 60 (56.6%) to
      several NSAIDs (multiple hypersensitivity), were included in a single-blinded
      drug challenge protocol with cumulative doses of 175 mg of celecoxib, 875 mg of
      paracetamol and 175 mg of nimesulide. Objective and subjective symptoms during
      challenge were documented. RESULTS: Of 261 challenges in 106 patients, 31
      challenges were positive: 5 of 106 (4.7%) for celecoxib, 10 of 64 (15.6%) for
      paracetamol and 16 of 91 for nimesulide (17.6%). Adverse reactions to celecoxib
      were mainly mild in character: three patients reported subjective symptoms
      including generalised pruritus and thoracic oppression, whereas two patients
      reacted with angio-oedema. CONCLUSIONS: Our results demonstrate that celecoxib is
      well tolerated by the majority of patients with NSAID intolerance. However, since
      adverse reactions to celecoxib cannot be ruled out completely, a controlled oral
      challenge test is still mandatory for proper management of patients with NSAID
      intolerance.

PMID- 17183431
TI  - A single dose of oral vitamin K effectively reverses oral anticoagulation with
      phenprocoumon during heart catheterisation.
AB  - QUESTION UNDER STUDY: To investigate the effectiveness of a single adjusted dose
      of oral vitamin K to temporarily reverse oral anticoagulation with phenprocoumon
      (Marcoumar) for heart catheterisation. METHODS: Patients under stable oral
      anticoagulation with phenprocoumon routinely scheduled for heart catheterizstion
      were given a single adjusted dose of oral vitamin K a day prior to the
      intervention. The customary anticoagulation scheme was kept unchanged with the
      exception of taking the double usual dose of phenprocoumon the evening after the
      intervention. The primary outcome was the achieved international normalised ratio
      (INR) immediately before the intervention. Secondary outcomes were the INR after
      one and four weeks, changes in phenprocoumon and coagulation factors II and VII
      and adverse events. RESULTS: 38 patients at a median age of 71 (63-74) years
      scheduled for heart catheterisation were included. The median INR changed from
      2.2 (1.9-2.6) the day before to 1.5 (1.4-1.7) immediately before the
      intervention. An INR < or =1.5 respectively < or =1.8 was achieved in 61% and 95%
      of the patients. The INR values after one respectively four weeks were comparable
      to preintervention values. No thromboembolic or bleeding adverse events occurred
      during the study. CONCLUSION: A single adjusted oral dose of vitamin K given a
      day prior to heart catheterisation combined with a doubled phenprocoumon dose on
      the procedure day seems to be an easy applicable, safe and effective way to
      temporary reverse oral anticoagulation with phenprocoumon.

PMID- 17183432
TI  - Anti-HLA antibody repertoire after IVIg infusion in highly sensitized patients
      waiting for kidney transplantation.
AB  - Polyclonal intravenous immunoglobulin (IVIg) treatment reduces crossmatch
      positivity and increases rates of transplantation in highly sensitised patients
      (HS). We quantified the panel reactive antibody (PRA) by microlymphocytotoxicity
      (MLCC), and we analysed anti-HLA class I and class II IgG specific antibody
      repertoire by Luminex before and after IVIg infusion alone in HS patients
      awaiting kidney transplantation. Five patients received three monthly infusions
      of 1 g/kg of IVIg. Serum samples collected pre and post IVIg treatment were
      submitted for PRA analysis by MLCC. Anti-class I and anti-class II antibody
      specificities were then tested by Luminex. We focused on the anti-HLA class I and
      class II antibodies directed against HLA expressed by a previous graft. We also
      analysed the anti-HLA antibody repertoire in three patients who had not received
      IVIg infusion. The PRA level determined by MLCC decreased significantly in one of
      the five patients, dropping from 40% to 17%. The Luminex assay showed
      fluctuations of the anti-HLA antibody levels over time, but no significant
      longterm modifications of the anti-HLA antibody repertoire were observed, even in
      the patient with a strong and prolonged reduction of the PRA determined by MLCC.
      Our results show that IVIg at 1 g/kg is not sufficient to reduce PRA and does not
      modify the repertoire of specific anti-HLA antibody determined by Luminex.

PMID- 17183433
TI  - Safety and outcome of patients with an acute ST-elevation myocardial infarction
      transferred for primary coronary intervention: the Neuchatel experience.
AB  - BACKGROUND: Transferring patients with ST-elevation myocardial infarction (STEMI)
      for primary percutaneous coronary intervention (PCI) from a community hospital to
      a PCI centre has been evaluated in randomised trials and shown to be safe and
      effective. A prolonged transfer time may restrict the benefit of this strategy.
      AIM: We sought to assess 1) safety of transfer from Neuchatel to Berne, 2) time
      intervals of patients transferred either directly from on-site or after
      evaluation in the local emergency room, and 3) clinical long-term outcome.
      METHODS AND RESULTS: 42 patients with STEMI eligible for reperfusion therapy were
      prospectively included between January 2003 and June 2004. Twenty patients (48%,
      group 1) were directly transferred to the PCI centre from on-site. Twenty-two
      were transferred after initial treatment in the local emergency room: 11 patients
      (26%, group 2) presented spontaneously at the hospital and 11 patients (26%,
      group 3) were admitted by the rescue team. No major complication occurred during
      transport. Median transport time was 33 minutes. Median time from first
      healthcare contact to balloon consisted of 131 minutes in group 1, 158 minutes in
      group 2 and 174 minutes in group 3. The overall rate of Major Adverse Cardiac
      Events (MACE) at 6 months amounted to 9.5%. CONCLUSIONS: Transfer for primary PCI
      of our patients with acute STEMI was safe. Direct transfer from on-site to the
      PCI centre reduced the time of ischaemia. The overall MACE rate was low.

PMID- 17183434
TI  - Life with a nightmare, or: if I had not been a doctor.

PMID- 17183435
TI  - Therapy and management of systemic AL (primary) amyloidosis.
AB  - The optimal treatment of immunoglobulin light chain amyloidosis (AL) patients
      requires early diagnosis, correct amyloid typing, effective treatment and careful
      supportive therapy. In the last few years the therapeutic arsenal for the
      management of AL has been considerably enriched. Cardiac dysfunction can be
      accurately monitored by measuring the serum concentration of natriuretic peptide
      type-B and cardiac troponins and the quantitative test for circulating free light
      chains allows an easy assessment of haematological response to chemotherapy.
      These new tools can be combined in order to maximise the improvement of organ
      dysfunction and minimise toxicity, adapting the intervention to each patient.

PMID- 17183436
TI  - Relationship between impaired functional stability and back pain in children: an
      exploratory cross-sectional study.
AB  - QUESTIONS UNDER STUDY: On surveys, about every fifth child in the school age
      reports back pain. There is a dearth of literature on the association between
      functional stability and back pain in children. OBJECTIVE: To examine the
      association between functional stability, measured with the Matthiasstest, and
      "back pain during the last week". METHODS: We used data from a cross-sectional
      survey on third, fourth and fifth grade school-years (128 children aged between 8
      and 12 years) in seven different classes in two different rural regions of
      Switzerland, to evaluate in an explorative manner the association between the
      score of the Matthiass-test and low back pain and upper back pain in the last
      week with two multivariable logistic regressions. RESULTS: The Matthiass-test
      score, controlled for age, sex and language region of the school, was
      significantly associated with low back pain in the last week (adjusted odds ratio
      1.77 with an 95% confidence interval from 1.08 to 2.91) and non significantly
      with the upper back pain in the last week (adjusted odds ratio 1.67 with an 95%
      confidence interval from 0.98 to 2.81). CONCLUSION: The Matthiass-test score is
      associated with low back pain. Because of the exploratory character of this
      study, these results should be regarded with caution. Whether a high score on the
      Matthiass-test could be a risk factor for back pain should be evaluated in
      prospective studies.

PMID- 17183438
TI  - Neurological adverse events to voriconazole: evidence for therapeutic drug
      monitoring.
AB  - BACKGROUND: Voriconazole shows a considerable interpatient variation of serum
      concentrations. METHODS AND RESULT: In an analysis of 28 treatment courses, 6
      patients presented with neurological adverse events (hallucination,
      encephalopathy, and visual disturbance). The hazard ratio per 0.1 mg/mL
      voriconazole serum level (sVL) increase was 2.27 (95% CI: 1.45-3.56, p <0.001).
      There was no correlation between sVL and creatinine (r = 0.12, p = 0.114), ALT (r
      = -0.14, p = 0.072), AST (r = 0.003, p = 0.964), alkaline phosphatase (r = 0.03,
      p = 0.723). CONCLUSIONS: Our findings demonstrate that elevated sVL is associated
      with neurological adverse events, and measurement of its serum concentration
      could improve voriconazole treatment and safety.

PMID- 17183437
TI  - Testing strategies and follow-up for coeliac disease in a general internal
      medicine outpatient department from 2000 to 2005.
AB  - PRINCIPLES: Coeliac disease (gluten sensitive enteropathy) is a genetically
      determined disorder with an incidence in the general population that is
      comparable to type 2 diabetes mellitus. Awareness of this fact and of the often
      atypical and oligosymptomatic manifestations is only now gaining ground in the
      medical profession. A high index of suspicion is important in order to minimise
      diagnostic and therapeutic delay. METHODS: Testing patterns and follow-up for
      coeliac disease in our institution have been analysed retrospectively for the
      past five years. The current literature was reviewed with respect to
      recommendations for clinical practice. RESULTS: A total of 271 patients were
      tested for coeliac disease over a period of five years. Only in 24 patients were
      positive results found; after further work-up, the final number of cases with
      certain or presumed coeliac disease was four. Followup was often difficult, many
      patients being lost after a single visit. CONCLUSIONS: This study showed that the
      number of tests ordered in our institution, more often for abdominal than
      atypical symptoms, has started to increase in the past two years. It also showed
      that screening tests have found their place in general clinical practice, while
      the final choice of tests needs to be determined in accordance with available
      guidelines and local resources. Upper endoscopy with small bowel biopsy remains
      the gold standard for diagnosis, but its place in follow-up is less certain.
      Coeliac disease is a disorder for which there is a definite treatment (gluten
      free diet); if it is left untreated diminished quality of life and potentially
      serious complications may ensue. Further education of the medical profession
      regarding coeliac disease, its incidence, presentation and treatment, is clearly
      indicated..

PMID- 17183440
TI  - [Incidence of postpartum depression in Trabzon province and risk factors at
      gestation].
AB  - OBJECTIVE: Risk of depression increases in some periods of the women's life and
      postpartum period is one of these periods. Women in the risk group should be
      followed-up both prenatally and postnatally. The aim of this study is to
      investigate the incidence and risk factors of postpartum depression in Trabzon
      province. METHOD: Among all pregnants in the third trimester of gestation
      attending to six primary health care centers belonging to Trabzon province and
      the Hospital of Obstetrics and Pediatrics were informed about the study and of
      these 316 person who accepted to attend the study were applied Sociodemographic
      Questionnary, General Health Inventory, Beck Anxiety Inventory, Beck Depression
      Inventory. Of these 192 women (75%) were reached at the first visit. At sixth
      eighth weeks of postpartum, above mentioned inventories, excluding
      Sociodemographic Questionnary but additionally Edinburgh Postnatal Depression
      Scale, were applied to 152 of these women (79%). All tests were re-applied to 132
      (68.7%) women at their sixth month after delivery. RESULTS: Incidence of DSD
      according to Edinburgh Postnatal Depression Scale was found 28.1% in Trabzon
      province. Reported depression after previous pregnancies, scores equal or above
      five in General Health Inventory in pregnancy and high scores in Beck Anxiety
      Inventory were determined as predictors of postpartum depression in the study
      population. CONCLUSION: As being the first follow up study of investigating the
      incidence of postpartum depression by a scale prepared to used this area, these
      findings are important to guide the further studies in connected with matter.

PMID- 17183441
TI  - [Relationship between attachment style and depressive symptoms in postpartum
      women: findings from Turkey].
AB  - OBJECTIVE: The present study aimed to investigate the association between
      depressive symptoms and attachment style in postpartum women in a non-western
      setting. METHOD: This study was carried out at the local health care centers in
      April 2004 among Turkish mothers within 2 to 18 months postpartum. A
      sociodemographic data sheet and the Turkish versions of Edinburgh Postnatal
      Depression Scale (EPDS) and Adult Attachment Style Questionnaire (AAQ) were
      administered to 80 mothers. RESULTS: On the EPDS, 30 % of the sample (n=24)
      displayed symptoms of depression with a cut-off score of >/=11. Postpartum
      depressive symptoms (EPDS >/= 11) were found to be associated with insecure
      attachment style (X2=4.42, p=0.035; X2=10.81, p=0.001 for Part 1 and Part 2 of
      AAQ, respectively). CONCLUSION: Maternal insecure attachment behavior, stimulated
      by the close relationship with the infant may contribute to the factors that may
      give rise to symptoms of depression. The present study, performed in a non
      western country, confirms the results of the previous western studies suggesting
      a relationship between insecure attachment style and postpartum depression (PPD).
      Clinicians should pay particular attention to vulnerable women regarding their
      attachment style for early identification and treatment of PPD, either in western
      or non-western societies.

PMID- 17183442
TI  - [Mental health of infertile women in Nigeria].
AB  - OBJECTIVE: To determine the prevalence of psychiatric morbidity and factors
      associated with poor mental health in women suffering from infertility. METHOD:
      The General Health Questionnaire (GHQ-30), Beck Depression Inventory (BDI) and
      the Anxiety Subscale of the Hospital Anxiety and Depression Scale (HADSA) were
      administered to 112 women with infertility at the time of their first
      presentation to a fertility clinic in a tertiary referral centre. The comparison
      group comprised of 96 women presenting at the family planning clinic of the same
      institution. In addition to demographic data, a structured questionnaire was used
      to collect obstetric information and clinical details from the participants.
      RESULTS: The prevalence of psychiatric morbidity was 46.4% (GHQ cases) in the
      infertile women, 37.5% and 42.9% were cases of anxiety and depression
      respectively. Women suffering from infertility scored significantly higher on all
      outcome measures of psychopathology. The results of the multiple regression
      analysis showed that the sociodemographic variables of the women with infertility
      contributed to the prediction of psychiatric morbidity (GHQ-30 score), because of
      the effects of age, not having at least one child and poor support from spouse (
      R2 =.26 Adjusted R2=.19 F(10,101)=3.57 p=.001). Lack of support from husband also
      predicted depression and anxiety. Low level of education, polygamous marriage,
      unemployment, lack of support from in-laws and duration of illness were not
      predictors of mental ill health. CONCLUSION: Infertility is associated with high
      levels of psychiatric morbidity. Our findings reinforce the need for
      gynaecologist and healthcare professionals to look for psychosocial distress in
      women undergoing fertility treatment. Psychological interventions and
      improvements in the organization of care is essential to positively impact on
      outcome during treatment in this group of women.

PMID- 17183443
TI  - [Traumatic life events and problem solving skills in psychiatric outpatients:
      relationships with suicidal behavior].
AB  - OBJECTIVE: To investigate the prevalence and the relationship of traumatic life
      events and problem solving skills to suicidal behavior in a group of psychiatric
      outpatients. METHOD: The study was conducted with 121 (57 % women) psychiatric
      outpatients. Patients who accepted participation filled in a questionnaire that
      contained questions about socio-demographics, clinical features, suicidal
      behavior, traumatic life-events, and a problem-solving inventory. Data were
      analyzed by means of t-tests, chi-square tests, one-way analysis of variance and
      multiple logistic regression analyses. RESULTS: Of the patients, 43.2 % (47.8 %
      women) reported having thought and 28.7 % (29.7 % women) reported having
      attempted suicide. 75.4 % of the sample experienced at least one traumatic life
      event. On average, a person experienced approximately 2 (SD = 1.7) traumatic
      events. Two logistic regression analyses showed that inefficient problem solving
      was an independent predictor of both suicidal thoughts and attempts. Number of
      traumatic events appeared to be an independent predictor of suicidal attempts
      after the problem solving skills. In accordance with diathesis-stress model, both
      suicidal thoughts and attempts were found to be most frequent among persons with
      inefficient problem solving skills and who were also exposed to a large amount of
      traumatic life events. CONCLUSION: Suicidal behavior and traumatic life events
      are common among psychiatric patients. Findings indicate that inefficient problem
      solving may be an independent predictor of both suicidal ideation and attempts.
      Suicidal behavior, traumatic life-events and problem solving skills should be
      addressed during psychiatric assessment. Study findings imply that problem
      solving therapy may be an important approach that can be used for the treatment
      of psychiatric patients exhibiting suicidal behavior.

PMID- 17183444
TI  - [The prevalence of generalized anxiety disorder and comorbidity among psychiatric
      outpatients].
AB  - OBJECTIVE: In this study, we aimed to investigate the prevalence, association
      with sociodemographic characteristics, and comorbidity with other anxiety and
      depressive disorders of generalized anxiety disorder (GAD) among psychiatric
      outpatients. METHOD: In the first phase of the study, outpatient psychiatry
      clinic physician interviewed with consecutive 950 patients who applied to
      psychiatry outpatient clinic of an university hospital by using GAD module of
      CIDI (Composite International Diagnostic Interview, version 2.1) during 4-month.
      Ninety-nine patients with diagnosis of GAD in the first phase were referred to
      the researcher physician for further evaluation. In the second phase, patients
      were interviewed by using CIDI anxiety and mood (major depression, dysthymic
      disorder) disorder modules. By this way, 12-month additional diagnoses were
      examined, and diagnosis of GAD was confirmed. One patient was excluded, because
      did not meet the GAD criteria during reexamination by the researcher physician.
      RESULTS: Ninety-eight patients (10.3%) met DSM-IV criteria for GAD. Eighty-nine
      (90.8%) of the cases had comorbid any anxiety or depressive disorder. The rates
      of comorbidity with any of depressive disorders and anxiety disorders were found
      84.7% and 56.1%, respectively. The most common comorbid diagnosis was major
      depression (83.7%). The most common anxiety disorders were social phobia (30.6%),
      OCD (19.4%) and specific phobia (17.4%). The prevalence of GAD was observed
      significantly higher in women, married ones, housewives, unworking girls,
      subjects with history of medical illness and lower educational status.
      CONCLUSION: Our results show that among psychiatric outpatients, GAD has high
      comorbidity rates with depressive and other anxiety disorders, and it is
      associate with some sociodemographic characteristics such as gender, and marital,
      working and educational status.

PMID- 17183445
TI  - [The parental bonding instrument: evaluation of psychometric properties with
      Turkish university students].
AB  - OBJECTIVE: The present study aimed to evaluate the psychometric properties of the
      Parental Bonding Instrument (PBI) for Turkish university students. METHOD: A
      total of 336 (% 61.5) female and 211 (%38.5) male students attending Ankara and
      Pamukkale Universities participated in the study. The mean age of the
      participants is 21.55 (SD=1.65) with a range of 18-26. The construct validity is
      examined by exploratory factor analysis; the criterion related validity is
      assessed by examining the correlation of the PBI with two instruments namely "The
      Parental Attitude Research Instrument (PARI)" and "The Parenting Style Inventory
      (PSI)". The reliability of the PBI was assessed by Cronbach's Alpha, test-retest
      and split-half reliability statistics. RESULTS: The factor analysis for Turkish
      university students yielded two factor solutions for both parents as original
      PBI. Nevertheless the items related to the controlling behaviors are loaded on
      the care factor instead of the overprotection as found by Parker et. al. (1979).
      Thus these two factors are named as care/control and overprotection subscales.
      Additionaly, PBI is found to demonstrate generally a high level of correlations
      with PARI and PSI supporting criterion-related validity. Finally, the reliability
      studies of the PBI demonstrated that it is a highly reliable scale and showed
      stability for a period of three weeks interval. CONCLUSION: The psychometric
      properties of the PBI is found to be satisfactory and could be used to assess
      parental attachment. It is suggested that further studies may illuminate the
      clinical value of the PBI and quantify parental contribution to psychopathology.

PMID- 17183446
TI  - [Does menstrual cycle affect mood disorders?].
AB  - OBJECTIVE: This paper will present a review of the literature on the relationship
      between the menstrual cycle and mood disorders. METHOD: We performed a MEDLINE
      search of the Turkish and English language literature for the years 1955-2005
      using the following terms: depression, bipolar disorder, premenstrual syndrome,
      premenstrual exacerbation, premenstrual dysphoric disorder, menstrual cycle, and
      suicide. Earlier reports had shown higher psychiatric admission during
      premenstrual period of the menstrual cycle and higher prevalence of suicide
      attempts during specific phase of the menstrual cycle. RESULTS: Women of
      reproductive age with mental disorders may experience a fluctuating course of
      illness over the menstrual cycle. Some data suggest that for a subset of women
      there is a relationship between phases of the menstrual cycle and increased
      vulnerability for an exacerbation of ongoing mood disorders (especially major
      depressive episode) or the development of a new episode. The question of whether
      the direction of mood shifts in the course of bipolar disorder is associated with
      specific cycle phase has been raised, albeit with limited and inconsistent data.
      CONCLUSION: There are a limited number of studies to elucidate these
      relationships and most of them lack prospective assessments, include the small
      number of patients and use unreliable methods of determining menstrual-cycle
      phases. Additionally, many reports do not specify whether the exacerbations
      reflect an aggravation of the underlying mood disorder or a new subset of
      symptoms that occur only during certain phases of the menstrual cycle. Further
      studies should provide more information about the contribution of premenstrual
      fluctuation or worsening to increased illness severity of mood disorder and
      treatment resistance.

PMID- 17183447
TI  - [Psychodermatology: a collaboration between psychiatry and dermatology].
AB  - Dermatology is of special importance in consultation-liaison practice. The brain
      and the skin originate from the same germ layer, the ectoderm, in the embryo. In
      later periods of life, the various ways these two organs influence each other has
      been the subject of many studies published in this field. These studies are
      divided into three groups: 1- studies about stress and dermatologic diseases, 2-
      psychoanalytic and psychodynamic approaches to psychodermatologic diseases, and 3
      clinical research and treatment of psychodermatologic diseases. Recently, in
      some countries which are aware of the importance of the subject, in the
      psychodermatology section psychiatrists, dermatologists, psychologists and
      residents work together as a team. In fact, it has been already accepted that
      there is a need for association between psychiatry and dermatology in many cases.
      This association between the two disciplines aims to enhance the success of
      therapy and psychiatric support for patients who primarily have psychiatric
      disease, but project that as a dermatologic disease, on the one hand. On the
      other hand, it provides a more holistic, and satisfying approach for both doctors
      and patients having primarily dermatologic disease, but who develop psychiatric
      problems secondarily. In this article, psychodermatology investigations and the
      relationship between the skin and psyche, diseases discussed in this context, and
      overlapping areas of psychiatry and dermatology are reviewed, and it is aimed to
      attract attention to this topic.

PMID- 17183448
TI  - Measuring the spatial arrangement patterns of pathological lesions in
      histological sections of brain tissue.
AB  - The development of abnormal protein aggregates in the form of extracellular
      plaques and intracellular inclusions is a characteristic feature of many
      neurodegenerative diseases such as Alzheimer's disease (AD), Creutzfeldt-Jakob
      disease (CJD) and the fronto-temporal dementias (FTD). An important aspect of a
      pathological protein aggregate is its spatial topography in the tissue. Lesions
      may not be randomly distributed within a histological section but exhibit spatial
      pattern, a departure from randomness either towards regularity or clustering.
      Information on the spatial pattern of a lesion may be useful in elucidating its
      pathogenesis and in studying the relationships between different lesions. This
      article reviews the methods that have been used to study the spatial topography
      of lesions. These include simple tests of whether the distribution of a lesion
      departs significantly from random using randomized points or sample fields, and
      more complex methods that employ grids or transects of contiguous fields and
      which can detect the intensity of aggregation and the sizes, distribution and
      spacing of the clusters. The usefulness of these methods in elucidating the
      pathogenesis of protein aggregates in neurodegenerative disease is discussed.

PMID- 17183449
TI  - Inhibition of mitochondrial complex II affects dopamine metabolism and decreases
      its uptake into striatal synaptosomes.
AB  - The mitochondrial toxin, 3-nitropropionic acid (3-NP), is a specific inhibitor of
      succinate dehydrogenase, complex II in the mitochondrial respiratory chain. The
      aim of our study was to determine the relationship between inhibition of
      mitochondrial complex II and dopamine (DA) metabolism and its transport into rat
      striatal synaptosomes after exposure to 3-NP. The study was carried out using
      spectrophotometric, radiochemical and HPLC methods. Our data showed that
      inhibition of succinate dehydrogenase by intraperitoneal (i.p.) injection of 3-NP
      (cumulated dose 100 mg/kg in 4 days) significantly affected DA metabolism,
      leading to the accumulation of its metabolites, 3,4-dihydroxylphenylacetic acid
      (DOPAC) and homovanillic acid (HVA) in the rat striatum. These experimental
      conditions had no effect on free radical dependent lipid peroxidation in the
      brain. In vitro experiments revealed that DA and DOPAC significantly decrease
      lipid peroxidation in the brain homogenate. Moreover, 3-NP significantly
      inhibited [3H]DA uptake into striatal synaptosomes by specific dopamine
      transporter (DAT). The scavengers of superoxide radical (O2-) Tempol and Trolox
      had no effect on DAT function, but the nitric oxide synthase (NOS) inhibitor N w
      nitro-L-arginine (100 microM) prevented 3-NP-evoked DAT down-regulation. In
      summary, our results indicate that inhibition of mitochondrial complex II by 3-NP
      enhances DA degradation and decreases its uptake into synaptosomes. It is
      suggested that NO and energy failure are responsible for alteration of the
      dopaminergic system in the striatum.

PMID- 17183450
TI  - Phenotypic diversity resulting from a point mutation.
AB  - Paralytic tremor (pt), a hereditary neurological disorder of rabbits, is a
      recessive, X-linked point mutation in exon 2 of the plp gene, responsible for
      substitution of 38 His by Glu in the PLP molecule. Pt genotype is expressed in a
      range of phenotypes, distinguished by the severity of neurological symptoms.
      Variable course of the disease, from totally asymptomatic to serious disorder, is
      observed even within the offspring of one breeding pair. The two most typical
      phenotypes have been chosen for the studies: one representing mild course of the
      disease and the other reflecting the most severe course. Since previous
      developmental studies proved that myelination is not only deficient but also
      delayed in pt rabbits, the age groups of animals have been selected with the aim
      of spanning the period of most active myelinogenesis. As revealed by experiments,
      the degree of CNS hypomyelination, which is the main future of pt mutation, is
      highest in the most affected animals. The amounts of mutated gene products, PLP
      and DM-20, examined both at mRNA and protein levels, exhibited a strong
      dependence on phenotype. Down-regulation of MBP and CNP was also observed. In
      contrast, MAG expression was normal or only slightly changed in mutants. The
      results lead to the conclusion that pt mutation in the plp gene affects a panel
      of events that governs myelinogenesis and is modulated in each individual that is
      manifested by gradation of neurological symptoms.

PMID- 17183451
TI  - TrkB deficiency increases survival and regeneration of spinal motoneurons after
      axotomy in mice.
AB  - Persisting motor function deficit after peripheral nerve injury often results
      from axotomized motoneuron death. Brain-derived neurotrophic factor (BDNF) and
      its receptor, trkB, are known to promote peripheral nerve regeneration. However,
      the requirement of BDNF and trkB for adult motoneuron survival after peripheral
      nerve injury is not established. We studied the number of surviving and
      regenerating motoneurons after sciatic nerve transection in wild-type and
      heterozygous trkB-deficient mice. The nerve was either left cut or immediately
      sewed up or the gap injury model was performed. The gap was provided with an
      autologous or cross (obtained from other genetic group) graft. Sixteen weeks
      after surgery, the animals were sacrificed and histological evaluations were
      performed. In order to study the number of regenerating motoneurons,
      immunofluorescent tracer was applied to the distal stump of the operated nerve.
      We found that in wild type mice, the decrease in motoneurons after nerve
      transection was markedly higher than in trkB-deficient animals, regardless of the
      operation procedure. Nerve transection resulted in the highest decrease in
      motoneuron number in wild type mice. This decrease was lower if the nerve was re
      joined using a cross-graft obtained from a trkB-deficient animal. Interestingly,
      in trkB-deficient animals, the decrease in motoneuron count did not depend on
      type of operation and was similar after nerve transection, re-joining or
      grafting. The number of regenerating motoneurons after nerve transection and re
      joining in wild type animals was lower than in trkB-deficient mice. The number of
      regenerating motoneurons after nerve grafting did not differ between groups.
      These results provide further evidence for the role of trkB receptor in spinal
      motoneuron survival and regeneration.

PMID- 17183453
TI  - Ultrastructural picture of blood vessels in muscle and skin biopsy in CADASIL.
AB  - CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy) is an inherited systemic vascular disorder affecting mainly
      the central nervous system. We performed detailed ultrastructural examination of
      the small vessels in the skin and skeletal muscle of a 51-year-old patient with
      bilateral cerebral white matter lesions, who had a history of two ischaemic
      strokes. The arterioles were characterized by degeneration and loss of vascular
      smooth muscle cells (VSMCs). GOM deposits, varied in size and shape, were located
      in the neighbourhood of the smooth muscle cells, often within an infolding of the
      cell membrane. No apparent correlations between presence, size or number of GOM
      deposits and damage severity of vascular smooth muscle cells were seen. Moreover,
      in some capillaries there were GOM deposits which were seen in the basement
      membrane near pericytes and endothelial cells. On the other hand, lesions of
      VMSCs and/or endothelial cells were also visible on the sections of blood vessels
      devoid of GOM deposits. Genetic tests detected a mutation in exon 4 of the Notch3
      gene. It confirmed the initial diagnosis which had been suggested on the basis of
      the clinical and MRI findings.

PMID- 17183452
TI  - Corticobasal degeneration -- clinico-pathological considerations.
AB  - Corticobasal degeneration (CBD) is a rare sporadic 4-repeat tauopathy. We report
      here the first Polish case of pathologically proven CBD. Our patient developed
      clumsiness of the right hand at age 63 years. During the course of his illness he
      suffered from progressive asymmetric parkinsonism unresponsive to dopaminergic
      therapy. Focal dystonia affecting right upper extremity, non-fluent aphasia,
      dysphagia, supranuclear vertical gaze palsy, imbalance and myoclonus ensued. The
      patient died of pneumonia at age 71 years. Head magnetic resonance imaging
      revealed the presence of asymmetric cortical atrophy contralateral to the
      clinically more affected right side. Median somatosensory evoked potentials
      performed bilaterally demonstrated significant reduction of cortical evoked
      potential amplitudes recorded from the left scalp electrodes. Neuropathological
      examination showed cortical atrophy of the frontal and parietal lobes with
      superficial spongiosis and diffuse cortical gliosis. Numerous ballooned neurons
      were found in frontal and parietal cortices. The most remarkable pathology was
      extensive tau-immunoreactivity of glial and neuronal cell processes,
      significantly pronounced in the frontotemporal cortex, basal ganglia, thalamus
      and brainstem. Recent research studies have resulted in better clinical,
      pathological and genetic characterization of sporadic tauopathies. It is hoped
      that similar progress will ensue in the development of symptomatic and eventually
      curative treatments for these rare conditions.

PMID- 17183454
TI  - Cerebellopontine angle tumours: radiologic-pathologic correlation and diagnostic
      difficulties.
AB  - A group of 119 cases of cerebellopontine angle (CPA) tumours was studied looking
      at the pathological composition, relative incidence of tumour types, their
      radiological features and the pathological-radiological correlations. Tumours
      with preoperative radiological diagnosis and verified pathologically were
      analyzed. Histopathologically the material consisted of 77 schwannomas and 42 non
      acoustic tumours. Radiological retrospective evaluation of CT and/or MRI
      documentation was performed in 84 patients. The tumours were classified according
      to Koos's staging scale. Diagnostic discrepancies (histopathological vs
      radiological) according to the clinical stage of CPA tumours were analyzed. In
      our series non-acoustic tumours made up 37% of CPA lesions. Sharp tumour-pyramis
      angle and intracanalicular fraction are not exclusive features of schwannomas.
      Tumours in stage IV are the most heterogeneous and diagnostically difficult
      group.

PMID- 17183455
TI  - Serial measurements of levels of the chemokines CCL2, CCL3 and CCL5 in serum of
      patients with acute ischaemic stroke.
AB  - Inflammation, involving cytokine/chemokine expression, occurs after stroke and
      deteriorates its course with leukocyte-mediated brain infarct progression.
      Chemokines are cytokines attracting selective leukocyte subsets and subgrouping
      into the four major subfamilies, CC, CXC, C, and CX3C. The CC subfamily
      preferentially acts on mononuclears. The study aimed to define serum CCL2, CCL3
      and CCL5 levels in stroke patients and their relationship to the extent of
      disease severity and outcome. 27 ischaemic stroke patients and 20 controls were
      studied. Blood sampling for the determination of chemokines was performed at days
      1, 2 and 3 of stroke, while neurological and functional deficits were estimated,
      respectively, with the Scandinavian Stroke Scale (SSS) and Barthel Index (BI) at
      the same time points and at days 14 and 28. Serum CCL3 levels at days 1, 2 and 3
      of stroke were significantly higher than in controls. Serum CCL2 and CCL5 levels
      in stroke patients did not differ from those in controls at any of the time
      points examined. Serum chemokine levels in stroke studied separately did not
      differ between each other at any time point studied and demonstrated considerable
      variability. No correlation between serum chemokine levels and SSS scores was
      observed. Serum CCL2 and CCL3 levels at days 1, 2 and 3 of stroke correlated with
      BI scores at day 28. Serum CCL2 levels at days 2 and 3 of stroke also correlated
      with BI scores at day 14. Serum CCL5 levels at day 2 of stroke correlated with BI
      scores at day 28. The early and sustained increase in serum CCL3 levels in stroke
      patients along with correlation between them and short-term poststroke functional
      disability could indicate that the chemokine response may predispose to poor
      stroke outcome. The relationship between non-increased serum CCL2 and CCL5 levels
      and worse stroke outcome seems to be coincidental. Overall, as a result of large
      interindividual variability, CCL2, CCL3 and CCL5 are not reliable candidates for
      surrogate markers in stroke.

PMID- 17183456
TI  - Hereditary neuropathy with liability to pressure palsy.
AB  - Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal
      dominant disease with sensory and motor nerve palsies usually precipitated by
      trivial trauma or compression. In the majority of cases HNPP is caused by
      deletion of the peripheral myelin protein 22 gene (PMP22) on chromosome 17p11.2.
      The authors present a family case with genetically proven HNPP.

PMID- 17183457
TI  - Malformations of cortical development in children: clinical manifestation,
      neuroimaging and neuropathology in selected cases.
AB  - Cerebral cortical development can be divided into three steps: cellular
      proliferation, neuronal migration and organization. Based on known pathologic,
      genetic and neuroimaging features a classification for malformations of cortical
      development was proposed by Barkovich in 2001, and updated in 2005. Malformations
      of cerebral cortex development (MCCD) often demonstrate epileptic seizures and
      delay in psychomotor development. About 20-40% of children with epilepsy are drug
      resistant and there is a large paediatric population requiring epilepsy surgery
      operations. In our work we performed clinical analysis of 68 children with MCCD
      treated in our hospital between 2000 and 2006. In our work to consider the type
      of MCCD we used the updated classification scheme proposed by Barkovich et al. We
      analyzed epilepsy, gestational and perinatal history, initial symptoms, time to
      establishing full diagnosis and neurodevelopmental/IQ status. In our results we
      found that despite similar clinical manifestation neuropathological basis could
      be significantly different, and vice versa: children with nearly identical
      neuropathological findings could have completely different neurological and
      radiological symptoms. Children with drug-resistant epilepsy are potential
      candidates for neurosurgical treatment; especially lesionectomies in such cases
      could be very promising in terms of epilepsy management and quality of life as
      well.

PMID- 17183458
TI  - Correlation of neuroradiological, electroencephalographic and clinical findings
      in cortical dysplasias in children.
AB  - INTRODUCTION: Cortical dysplasias (CD) are defined as malformations of cortical
      development. They result from impairment of neuronal proliferation, migration and
      differentiation. CD are common pathological substrates in patients with early
      onset childhood epilepsy and/or developmental delay as well as neurological
      signs. Recognition of the importance of cortical dysplasias has been shown in
      many studies when introducing structural MRI. The following study was performed
      in order to correlate the neuroimaging findings with the electroencephalographic
      and clinical picture of children with cortical dysplasias. MATERIALS AND METHODS:
      46 patients with the presence of CD features in MRI were identified. There were
      18 female and 28 male patients. The age ranged from 3 months to 12 years (mean
      age = 6.2, median age = 3.1). The objectives of the study were explained to the
      parents or legal representatives of children when possible and also informed
      consent was obtained. Multiple EEG recordings as well as detailed clinical
      analysis of all patients were performed. Statistical analysis was conducted in
      order to correlate the type of CD with clinical outcome and electrophysiological
      findings. RESULTS: There were 31 patients with focal dysplasias, 6 with
      schizencephaly, 4 with heterotopias, 3 lissencephaly and 2 with band heterotopia.
      80% presented epilepsy (60% of them drug-resistant). Additionally, we tried to
      elucidate the clinical characteristics of epilepsy. In 75% of epilepsy patients
      the electroencephalographic changes correlated with anatomical localization of
      CD. 74% of patients were mentally retarded and 30% had focal neurological
      deficits. CONCLUSIONS: There were no correlations between the type of CD and the
      severity of the clinical picture, especially the level of mental retardation and
      presence of drug-resistant epilepsy. Different age at epilepsy onset and various
      responsiveness to antiepileptic drugs in the majority of patients may reflect
      different dynamics in epileptogenicity of the underlying CD.

PMID- 17183459
TI  - Cerebral childhood and adolescent X-linked adrenoleukodystrophy. Clinical
      presentation, neurophysiological, neuroimaging and biochemical investigations.
AB  - Clinical, neurophysiological, neuroimaging and biochemical studies were performed
      in five boys with childhood and adolescent form of cerebral X-ALD, which is a
      very rare disease in developmental age. In all patients, rapidly progressive
      spasticity, ataxia and mental deterioration were found. Seizures occurred in four
      of them. Additionally, visual and hearing impairment were observed in four and
      three patients respectively. Adrenal insufficiency was also diagnosed in four
      cases. MR revealed extensive demyelination located mainly symmetrically in the
      parieto-occipital areas, in one patient in whom asymmetrical lesions in that
      region were found. All patients had abnormal visual, brainstem and somatosensory
      evoked potentials recording, reflecting the central demyelination occurring in X
      ALD. The clinical diagnosis in every case was confirmed by the significantly
      elevated concentration of very long chain fatty acids (VLCFA) measured in plasma
      in comparison to normal values.

PMID- 17183460
TI  - Faulty position of cerebellar cortical neurons as a sequel of disturbed neuronal
      migration.
AB  - The object of our report is the presentation of the morphological picture of
      cerebellar cortex malformation as a sequel of disturbed neuronal migration. In
      the disarranged tissue, cavities with a network of meningeal tissue and embedded
      pathological vessels were noted. The external granule cells did not form a proper
      external granule layer, but moved deeper, forming irregular aggregates.
      Abnormally aggregated external granular cells invaded the cerebellar tissue.
      Abnormal Purkinje cell positioning and a disarranged molecular layer were
      observed. The normal layered pattern of the cerebellar cortex was disorganized.
      The presented cases represent a spectrum of morphological changes which are the
      consequence of aberrant migration. Against a background of vascular pathology
      affecting the meningoglial network the migration pathways were disrupted. The
      defective movement of neurons and their faulty maturation resulted in
      disturbances of cortical layering, and defects of cerebellar folia formation.

PMID- 17183461
TI  - A history of normal plates, tables and stages in vertebrate embryology.
AB  - Developmental biology is today unimaginable without the normal stages that define
      standard divisions of development. This history of normal stages, and the related
      normal plates and normal tables, shows how these standards have shaped and been
      shaped by disciplinary change in vertebrate embryology. The article highlights
      the Normal Plates of the Development of the Vertebrates edited by the German
      anatomist Franz Keibel (16 volumes, 1897-1938). These were a major response to
      problems in the relations between ontogeny and phylogeny that amounted in
      practical terms to a crisis in staging embryos, not just between, but (for some)
      also within species. Keibel's design adapted a plate by Wilhelm His and tables by
      Albert Oppel in order to go beyond the already controversial comparative plates
      of the Darwinist propagandist Ernst Haeckel. The project responded to local
      pressures, including intense concern with individual variation, but recruited
      internationally and mapped an embryological empire. Though theoretically
      inconclusive, the plates became standard laboratory tools and forged a network
      within which the Institut International d'Embryologie (today the International
      Society of Developmental Biologists) was founded in 1911. After World War I,
      experimentalists, led by Ross Harrison and Viktor Hamburger, and human
      embryologists, especially George Streeter at the Carnegie Department of
      Embryology, transformed Keibel's complex, bulky tomes to suit their own
      contrasting demands. In developmental biology after World War II, normal stages
      reduced to a few journal pages-helped domesticate model organisms. Staging
      systems had emerged from discussions that questioned the very possibility of
      assigning an embryo to a stage. The historical issues resonate today as
      developmental biologists work to improve and extend stage series, to make results
      from different laboratories easier to compare and to take individual variation
      into account.

PMID- 17183462
TI  - XSu(H)2 is an essential factor for gene expression and morphogenesis of the
      Xenopus gastrula embryo.
AB  - The CSL (CBF-1, Suppressor of Hairless, Lag-1) transcriptional factor is an
      important mediator of Notch signal transduction. It plays a key role in cell fate
      determination by cell-cell interaction. CSL functions as a transcriptional
      repressor before the activation of Notch signaling. However, once Notch signaling
      is activated, CSL is converted into a transcriptional activator. It remains
      unclear if CSL has any function during early development before neurogenesis,
      while transcriptional products exist from the maternal stage. Here, we analyzed
      the function of Xenopus Suppressor of Hairless (XSu(H)) using morpholino
      antisense oligonucleotides (MO), which interfere with the translation of
      transcripts. In Xenopus embryos, maternal transcripts of both XSu(H)1 and XSu(H)2
      were ubiquitously observed until the blastula stage and thereafter only XSu(H)1
      was zygotically transcribed. Knockdown experiments with MO demonstrated that
      XSu(H)2 depletion caused a decrease in the expression of the Xbrachyury, MyoD and
      JNK1 genes. Morphological and histological examinations indicated that XSu(H)2
      depletion caused abnormal gastrulation, which resulted in severe defects of the
      notochord and somitic mesoderm. The effect of XSu(H)2-MO was completely rescued
      by co-injection of XSu(H)2 mRNAs, but not by XSu(H)1 mRNAs. XESR-1, a Notch
      signaling target gene, inhibited Xbrachyury expression. However, expression of
      the XESR-1 gene was not induced by depletion of XSu(H)2. Co-injection of the
      dominant-negative form of XESR-1 could not rescue the suppression of Xbrachyury
      expression in the XSu(H)2-depleted embryo. These results suggest that XSu(H)2 is
      involved in mesoderm formation and the cell movement of gastrula embryos in a
      different manner from the XESR-1-mediated Notch signaling pathway.

PMID- 17183463
TI  - Blood vessel/epicardial substance (bves) expression, essential for embryonic
      development, is down regulated by Grk/EFGR signalling.
AB  - The Pop1/Bves (blood vessel/epicardial substance) gene is a member of the popeye
      gene family recently identified in various species. It encodes a potential
      transmembrane glycoprotein and is a cell adhesion molecule present in skeletal
      and cardiac muscle and epithelia. We isolated the Drosophila homologue of Bves
      (DmBves) and found, using in situ hybridisation to RNA in ovaries, that bves is
      expressed in all follicular epithelial cells surrounding the oocyte at stage 10,
      except those in very posterior and anterior-dorsal regions adjacent to the
      oocyte. We show that the repression of bves expression in anterior-dorsal
      follicle cells is regulated by the Grk/EGFR signalling pathway. Bves is also
      expressed in nurse cells during oogenesis and its transcripts are then
      translocated into the oocyte. Expression of bves antisense RNA during oogenesis
      causes reduced viability in the resulting embryos. There is a failure in the
      migration of pole cells from the posterior towards the antero-dorsal side of the
      embryo, probably resulting from abnormal germband extension and we suggest that
      bves is essential for normal embryonic development.

PMID- 17183464
TI  - Induction of reverse development in two marine Hydrozoans.
AB  - Cnidarians are unique organisms in the animal kingdom because of their unequalled
      potential to undergo reverse development (RD). The life cycle of some species can
      temporarily shift ordinary, downstream development from zygote to adult into the
      opposite ontogenetic direction by back-transformation of some life stages. The
      potential for RD in cnidarians offers the possibility to investigate how
      integrative signalling networks operate to control directionality of ontogeny
      (reverse vs. normal development). Striking examples are found in some hydrozoans,
      where RD of medusa bud or liberated medusa stages leads to rejuvenation of the
      post-larval polyp stage. Artificial stress may determine ontogeny reversal. We
      describe here the results of experimental assays on artificial induction of RD by
      different chemical and physical inducers on two marine hydrozoans, Turritopsis
      dohrnii and Hydractinia carnea, showing a different potential for RD. A cascade
      of morphogenetic events occurs during RD by molecular mechanisms and cellular
      patterns recalling larval metamorphosis. For the first time, we show here that
      exposure to cesium chloride (CsCl), an inducer of larval metamorphosis, may also
      induce RD, highlighting similarities and differences between these two master
      ontogenetic processes in cnidarians.

PMID- 17183465
TI  - Stage-specific regulation of programmed cell death during oogenesis of the medfly
      Ceratitis capitata (Diptera, Tephritidae).
AB  - In the present study, we describe novel features of programmed cell death in
      developing egg chambers occurring during mid- and late-oogenesis of the medfly
      Ceratitis capitata. During mid-oogenesis, the spontaneously degenerated egg
      chambers exhibit typical characteristics of apoptotic cell death. Their nurse
      cells contain fragmented DNA and fragmented actin, as revealed by TUNEL assay and
      immunolabelling, respectively. In vitro caspase activity assays and
      immunostaining procedures demonstrated that the atretic egg chambers acquired
      high levels of caspase activity. Distinct features of autophagic cell death were
      also observed during C. capitata mid-oogenesis, as revealed by the
      monodansylcadaverine staining approach and ultrastructural examination performed
      by transmission electron microscopy. Additionally, atretic egg chambers exhibit
      an upregulation of lysosomal proteases, as demonstrated by a procathepsin L
      immunolabelling procedure. At the late stages of C. capitata oogenesis, apoptosis
      and autophagy coexist, manifesting cell death features that are similar to the
      ones mentioned above, being also chaperoned by the involvement of an altered
      cytochrome c conformational display. We propose that apoptosis and autophagy
      operate synergistically during C. capitata oogenesis for a more efficient
      elimination of the degenerated nurse cells and abnormal egg chambers.

PMID- 17183466
TI  - Amniotic fluid induces rapid epithelialization in the experimentally ruptured
      fetal mouse palate--implications for fetal wound healing.
AB  - Cleft of the secondary palate is one of the most common congenital birth defects
      in humans. The primary cause of cleft palate formation is a failure of fusion of
      bilateral palatal shelves, but rupture of the once fused palate has also been
      suggested to take place in utero. The possibility of post-fusion rupture of the
      palate in humans has hardly been accepted, mainly because in all the cleft palate
      cases, the cleft palatal edge is always covered with intact epithelium. To verify
      whether the intrauterine environment of the fetus plays roles in wound healing
      when the once fused palate is torn apart, we artificially tore apart fetal mouse
      palates after fusion and cultivated them in culture medium with or without mouse
      or human amniotic fluid. We thereby found that the wounded palatal edge became
      completely covered with flattened epithelium after 36 hours in culture with
      amniotic fluid, but not in culture without amniotic fluid. Using histological and
      scanning electron microscopic analyses of the healing process, it was revealed
      that the epithelium covering the wound was almost exclusively derived from the
      adjacent nasal epithelium, but not from the oral epithelium. Such actions of
      amniotic fluid on the fetal wound were never simulated by exogenous epidermal
      growth factor (EGF), albumin, or both. In addition, the rapid epithelialization
      induced by amniotic fluid was not prevented by either PD168393 (an inhibitor of
      the EGF receptor-specific tyrosine kinase) or SB431542 (a specific inhibitor of
      TGFbeta receptor type I/ALK5). The present study provides new insights into the
      unique biological actions of amniotic fluid in the repair of injured fetal
      palate.

PMID- 17183467
TI  - A change in response to Bmp signalling precedes ectodermal fate choice.
AB  - Bone morphogenetic protein (Bmp) signalling plays a central role in the decision
      of ectoderm to adopt either neural or non-neural fates. The effects of this
      signalling are seen at mid-gastrulation in the activation of genes such as the
      Gata factors and the repression of genes such as the SoxB1 transcription factors
      in the non-neural regions. Using zebrafish embryos, we show that this Bmp
      signalling does not repress the expression of these same neural markers just 2-3
      hours earlier. Since expression of the Bmp signalling effector, Smad1, only
      begins during early gastrulation, we tested the role of Smad1 and Smad5 (which is
      maternally expressed) in controlling gene expression both before and during
      gastrulation. This showed that the absence of Smad1 does not explain the lack of
      response of neural genes to Bmp signalling at early stages. However, these
      experiments showed that expression of the non-neural marker, gata2, is mediated
      by Smad5 in the absence of Smad1 at early stages, but is dependent upon Smad1 at
      later stages. Hence, we have shown a dynamic change in the molecular machinery
      underlying the Bmp response in the ectoderm during gastrulation stages of
      development.

PMID- 17183468
TI  - Enhanced development of porcine embryos cloned from bone marrow mesenchymal stem
      cells.
AB  - In the present study, we have characterized an isolated population of porcine
      bone marrow mesenchymal stem cells (MSCs) for multilineage commitment and
      compared the developmental potential of cloned embryos with porcine MSCs and
      fetal fibroblasts (FFs). MSCs exhibited robust alkaline phosphatase activity and
      later transformed into mineralized nodules following osteoinduction. Furthermore,
      MSCs underwent adipogenic and chondrogenic differentiation by producing lipid
      droplets and proteoglycans, respectively. Primary cultures of FFs from a female
      fetus at ~30 day of gestation were established. Donor cells at 3-4 passage were
      employed for nuclear transfer (NT). Cell cycle analysis showed that the majority
      of MSCs in confluence were in the G0/G1 stage. Cumulus-oocyte complexes were
      matured and fertilized in vitro (IVF) as control. The cleavage rate was
      significantly (P<0.05) higher in IVF than in NT embryos with MSCs and FFs
      (84.54.6% vs. 52.25.4% and 50.85.2%, respectively). However, blastocyst rates in
      IVF and NT embryos derived from MSCs (20.62.5% and 18.43.0%) did not differ, but
      were significantly (P<0.05) higher than NT derived from FFs (9.52.1%). Total cell
      number and the ratio of ICM to total cells among blastocysts cloned from MSCs
      (34.45.2 and 0.380.08, respectively) were significantly (P<0.05) higher than
      those from FFs (22.65.5 and 0.180.12, respectively). Proportions of TUNEL
      positive cells in NT embryos from FFs (7.31.8%) were significantly (P<0.05)
      higher than in MSCs (4.61.3%) and IVF (2.50.9%). The results clearly demonstrate
      that multipotent bone marrow MSCs have a greater potential as donor cells than
      FFs in achieving enhanced production of cloned porcine embryos.

PMID- 17183469
TI  - Genetic diversity in wild (Sus scrofa scrofa) and domestic (Sus scrofa domestica)
      pigs and their hybrids based on polymorphism of a fragment of the D-loop region
      in the mitochondrial DNA.
AB  - We examined the variation in mitochondrial DNA by sequencing the D-loop region in
      wild and domestic (large-white breed) pigs, in hybrids between domestic and wild
      pigs, and in Monteiro pigs. A D-loop fragment of approximately 330 bp was
      amplified by PCR. Sequencing of DNA amplicons identified haplotypes previously
      described as European and Asian types. Monteiro pigs and wild pigs had European
      haplotypes and domestic pigs had both European and Asian haplotypes.

PMID- 17183470
TI  - Genetic correlation between heifer pregnancy and scrotal circumference measured
      at 15 and 18 months of age in Nellore cattle.
AB  - Data of pregnancy diagnosis from 24,945 Nellore heifers, raised under tropical
      conditions in Brazil and exposed to breeding at about 14 months of age, were
      analyzed simultaneously with 13,742 (analysis 1), 36,091 (analysis 2), 8,405
      (analysis 3), and 8,405 (analysis 4) scrotal circumference (SC) records of
      contemporary young bulls in order to estimate heritability (h(2)) for yearling
      heifer pregnancy (HP) and for SC measured at around 15 (SC15) and 18 (SC18)
      months of age and to estimate genetic correlation between HP and SC15 (SC18).
      Heifer pregnancy was considered as a categorical trait, with the value 1
      (success) assigned to heifers that were detected as pregnant by rectal palpation
      approximately 60 days after the end of a 90-day breeding season and the value 0
      (failure) otherwise. In analyses 1 and 3, SC was measured at around 15 months of
      age and in analysis 2 and 4 it was measured at around 18 months of age. Only
      8,848 animals from datasets 1 and 2 were common in both files, which means the
      same animals measured at different ages. Datasets used in analyses 3 and 4
      included the same animals, measured at 15 and at 18 months of age, respectively.
      Heritability estimates for HP were similar in all analyses, with values ranging
      from 0.66 +/- 0.08 to 0.67 +/- 0.008. For SC15, the estimates were 0.57 +/- 0.05
      in analysis 1 and 0.60 +/- 0.07 in analysis 3. For SC18, the estimates were 0.53
      +/- 0.03 in analysis 2 and 0.64 +/- 0.06 in analysis 4. The estimates of genetic
      correlation between HP and SC15 were 0.15 +/- 0.10 in analysis 1 and 0.11 +/-
      0.11 in analysis 3. For the correlation between HP and SC18, the values were 0.27
      +/- 0.10 in analysis 2 and 0.16 +/- 0.11 in analysis 4. Based on standard errors
      and confidence intervals, the best heritability and genetic correlation estimates
      were obtained from analysis 2, which included more data and a better pedigree
      structure. Pearson correlation between HP and SC breeding values was similar to
      the genetic correlation estimates obtained from two-trait models, when all
      animals in the pedigree file were considered for its calculation. If only sires
      were considered for the calculation, Pearson correlation was higher but the
      pattern was the same as from two-trait analyses. The high heritability estimates
      obtained in the present study confirm that expected progeny difference (EPD) for
      HP can be used to select bulls for the production of precocious daughters and
      that the low genetic correlation between SC and HP indicates a greater efficacy
      of selection based on heifer pregnancy EPD than of selection based on scrotal
      circumference EPD. The results of the present study, although not conclusive,
      indicate that SC measured at around SC18 would have a higher genetic correlation
      with HP than would SC measured at around SC15.

PMID- 17183471
TI  - 'Ovar-Mhc' - ovine major histocompatibility complex: structure and gene
      polymorphisms.
AB  - The major histocompatibility complex (MHC) in sheep, Ovar-Mhc, is poorly
      characterised, when compared to other domestic animals. However, its basic
      structure is similar to that of other mammals, comprising class I, II and III
      regions. Currently, there is evidence for the existence of four class I loci. The
      class II region is better characterised, with evidence of one DRA, four DRB (one
      coding and three non-coding), one DQA1, two DQA2, and one each of the DQB1, DQB2,
      DNA, DOB, DYA, DYB, DMA, and DMB genes in the region. The class III region is the
      least characterised, with the known presence of complement cascade (C4, C2 and
      Bf), TNFalpha and CYP21 genes. Products of the class I and II genes, MHC
      molecules, play a pivotal role in antigen presentation required for eliciting
      immune responses against invading pathogens. Several studies have focused on
      polymorphisms of Ovar-Mhc genes and their association with disease resistance.
      However, more research emphasis is needed on characterising the remaining Ovar
      Mhc genes and developing simplified and cost-effective methods to score gene
      polymorphisms. Haplotype screening, employing multiple markers rather than single
      genes, would be more meaningful in MHC-disease association studies, as it is well
      known that most of the MHC loci are tightly linked, exhibiting very little
      recombination. This review summarises the current knowledge of the structure of
      Ovar-Mhc and polymorphisms of genes located in the complex.

PMID- 17183472
TI  - Identification of a new Schistosoma mansoni membrane-bound protein through
      bioinformatic analysis.
AB  - Progress in schistosome genome research has enabled investigators to move rapidly
      from genome sequences to vaccine development. Proteins bound to the surface of
      parasites are potential vaccine candidates, or they can be used for diagnosis. We
      analyzed 4342 proteins deduced from the Schistosoma mansoni transcriptome with
      bioinformatic computer programs. Thirty-four proteins had membrane-bound motifs.
      Within this group, we selected the Sm29 protein to be further characterized by in
      silico analysis. Sm29 was found to have a signal peptide made up of 26 amino
      acids, with a cleavage site between Ser26 and Val27. The glycosylation site
      search revealed three threonines (39, 132 and 133) with high probability of O
      glycosylation and two asparagines (58 and 115) with high probability of N
      glycosylation. Only one transmembrane helix was found in the C-terminal region of
      the protein from Leu169 to Lis191. The search for similarities and conserved
      motifs show that Sm29 is a protein with high identity to proteins present in S.
      japonicum (53, 52, 49, and 37% of identity) and it possesses disulfide-rich
      conserved domains. Apparently, Sm29 is a membrane bound protein, and it may be an
      important molecule in host-parasite interactions.

PMID- 17183473
TI  - Genuine Bayesian multiallelic significance test for the Hardy-Weinberg
      equilibrium law.
AB  - Statistical tests that detect and measure deviation from the Hardy-Weinberg
      equilibrium (HWE) have been devised but are limited when testing for deviation at
      multiallelic DNA loci is attempted. Here we present the full Bayesian
      significance test (FBST) for the HWE. This test depends neither on asymptotic
      results nor on the number of possible alleles for the particular locus being
      evaluated. The FBST is based on the computation of an evidence index in favor of
      the HWE hypothesis. A great deal of forensic inference based on DNA evidence
      assumes that the HWE is valid for the genetic loci being used. We applied the
      FBST to genotypes obtained at several multiallelic short tandem repeat loci
      during routine parentage testing; the locus Penta E exemplifies those clearly in
      HWE while others such as D10S1214 and D19S253 do not appear to show this.

PMID- 17183474
TI  - New evidence for nucleolar dominance in hybrids of Drosophila arizonae and
      Drosophila mulleri.
AB  - Drosophila mulleri (MU) and D. arizonae (AR) are cryptic species of the mulleri
      complex, mulleri subgroup, repleta group. Earlier cytogenetic studies revealed
      that these species have different regulatory mechanisms of nucleolar organizing
      activity. In these species, nucleolar organizing regions are found in both the X
      chromosome and the microchromosome. In the salivary glands of hybrids between MU
      females and AR males, there is an interspecific dominance of the regulatory
      system of the D. arizonae nucleolar organizer involving, in males, amplification
      and activation of the nucleolar organizer from the microchromosome. The authors
      who reported these findings obtained hybrids only in that cross-direction. More
      recently, hybrids in the opposite direction, i.e., between MU males and AR
      females, have been obtained. The purpose of the present study was to evaluate, in
      these hybrids, the association of the nucleoli with the chromosomes inherited
      from parental species in order to cytogenetically confirm the dominance patterns
      previously described. Our results support the proposed dominance of the AR
      nucleolar organizer activity over that of MU, regardless of cross-direction.

PMID- 17183475
TI  - Congenital bilateral anorchia: hormonal, molecular and imaging study of a case.
AB  - The aetiology of congenital bilateral anorchia is unknown. For many years there
      was speculation of an association between genetic factors and anorchia. We
      performed different tests in an anorchid boy, 2.5 years old, presented to us with
      micropenis and absence of both testes, in order to determine any possible factors
      contributing to the anorchia. Physical examination and hormonal, imaging,
      chromosomal, and molecular analyses of this case were performed. The basal FSH
      and LH levels were increased, and their increase in response to gonadotrophin
      releasing hormone test was prolonged, while testosterone levels failed to
      increase after hCG administration. Ultrasonography of the pelvis and magnetic
      resonance of the abdomen were performed and failed to show any testicular tissue.
      Lastly, surgical exploration confirmed the absence of testicular structure.
      Chromosomal analysis revealed a normal male karyotype and molecular analysis did
      not reveal mutations or polymorphisms in the open reading frame of the SRY gene.
      Diagnostically, the lack of testosterone response to hCG stimulation is the
      hormonal hallmark of bilateral congenital anorchia. In addition, according to our
      case and previous studies, there is lack of association between genetic factors
      necessary for correct testicular descent and anorchia.

PMID- 17183476
TI  - Use of RAPD fingerprinting for delineating populations of hilsa shad Tenualosa
      ilisha (Hamilton, 1822).
AB  - RAPD was used to delineate the hilsa populations sampled from the Ganga, Yamuna,
      Hooghly, and Narmada Rivers at six different locations. Six degenerate primers
      were used to generate the fragment patterns from the samples collected. All
      primers were highly polymorphic and generated high numbers of amplification
      products. Nei's genetic distances were calculated between locations. The overall
      average genetic distance among all the six locations was 0.295. The Fst value
      within the Ganga was 0.469 and within the Hooghly it was 0.546. The overall Fst
      value for the six populations analyzed was 0.590. The UPGMA dendrogram clustered
      the hilsa into two distinct clusters: Ganga and Yamuna populations and the
      Hooghly and Narmada populations.

PMID- 17183477
TI  - Construction and partial characterization of a Corynebacterium pseudotuberculosis
      bacterial artificial chromosome library through genomic survey sequencing.
AB  - Corynebacterium pseudotuberculosis is a gram-positive bacterium that causes
      caseous lymphadenitis in sheep and goats. However, despite the economic losses
      caused by caseous lymphadenitis, there is little information about the molecular
      mechanisms of pathogenesis of this bacterium. Genomic libraries constructed in
      bacterial artificial chromosome (BAC) vectors have become the method of choice
      for clone development in high-throughput genomic-sequencing projects. Large
      insert DNA libraries are useful for isolation and characterization of important
      genomic regions and genes. In order to identify targets that might be useful for
      genome sequencing, we constructed a C. pseudotuberculosis BAC library in the
      vector pBeloBAC11. This library contains about 18,000 BAC clones, with inserts
      ranging in size from 25 to 120 kb, theoretically representing a 390-fold coverage
      of the C. pseudotuberculosis genome (estimated to be 2.5-3.1 Mb). Many genomic
      survey sequences (GSSs) with homology to C. diphtheriae, C. glutamicum, C.
      efficiens, and C. jeikeium proteins were observed within a sample of 215
      sequenced clones, confirming their close phylogenetic relationship. Computer
      analyses of GSSs did not detect chimeric, deleted, or rearranged BAC clones,
      showing that this library has low redundancy. This GSSs collection is now
      available for further genetic and physical analysis of the C. pseudotuberculosis
      genome. The GSS strategy that we used to develop our library proved to be
      efficient for the identification of genes and will be an important tool for
      mapping, assembly, comparative, and functional genomic studies in a C.
      pseudotuberculosis genome sequencing project that will begin this year.

PMID- 17183478
TI  - The Candida albicans AAA ATPase homologue of Saccharomyces cerevisiae Rix7p
      (YLL034c) is essential for proper morphology, biofilm formation and activity of
      secreted aspartyl proteinases.
AB  - Proper morphology is essential for the ability of Candida albicans to switch
      between yeast and hyphae and thereby sustain its virulence. Here we identified,
      by differential screening, a novel C. albicans AAA ATPase encoding gene, CaYLL34
      (RIX7), with enhanced expression in hyphae. Phylogenetic analysis suggests that
      CaYLL34 belongs to a "VCP-like" subgroup of AAA ATPases essential for yeast
      viability and contains a bipartite nuclear localization signal. Inactivation of
      one copy of CaYLL34, by the URA-Blaster method, generated the heterozygous mutant
      strain M61. This strain has severe phenotypic alterations, such as a highly
      increased vacuole, abnormal cell shape and reduced growth in different
      conditions. Also, major pathogenicity factors are affected in M61, for instance,
      a significant decrease of hypha formation (>90%), surface biofilm adhesion (86%)
      and secreted aspartyl proteinase activity (76.5%). Our results show that the
      partial impairment of CaYll34p cellular levels is sufficient to affect the proper
      cellular morphology and pathogenicity factors and suggest that this protein is
      required for biogenesis of ribosomal subunits. Accordingly, we propose that the
      product of CaYLL34 could be tested as a novel target for antifungal drugs.

PMID- 17183479
TI  - Cassava in South America, Brazil's contribution and the lesson to be learned from
      India.
AB  - South America is responsible for about half of the cassava world production. In
      the 1970's productivity of the crop on the continent was about 15 ton/ha, and
      dropped continuously until reaching 12 ton/ha in 2004. India's productivity of
      cassava increased from 10 ton/ha in the 1970's to 28 ton/ha in 2004. Brazil
      contributed significantly to improving cassava crops through the Instituto
      Agronomico de Campinas in the 1960's and 1970's. The Universidade de Brasilia
      released high-protein content hybrids, apomictic clones and explored the
      potential of indigenous landraces.

PMID- 17183480
TI  - Comparative analysis of human masculinity.
AB  - To study rapidly evolving male specific Y (MSY) genes we retrieved and analyzed
      nine such genes. VCY, HSFY and RBMY were found to have functional X gametologs,
      but the rest did not. Using chimpanzee orthologs for XKRY, CDY, HSFY, PRY, and
      TSPY, the average silent substitution is estimated as 0.017 +/- 0.006/site and
      the substitution rate is 1.42 x 10(-9)/site/year. Except for VCY, all other loci
      possess two or more pseudogenes on the Y chromosome. Sequence differences from
      functional genes show that BPY2, DAZ, XKRY, and RBMY each have one pseudogene for
      each one that is human specific, while others were generated well before the
      human-chimpanzee split, by means of duplication, retro-transposition or
      translocation. Some functional MSY gene duplication of VCY, CDY and HSFY, as well
      as X-linked VCX and HSFX duplication, occurred in the lineage leading to humans;
      these duplicates have accumulated nucleotide substitutions that permit their
      identification.

PMID- 17183481
TI  - Hemoglobin I-Philadelphia [alpha 16 (A14) LYS-->GLU] heterozygote among blood
      donors from Brazil.
AB  - We describe a heterozygous case of Hb I-Philadelphia [alpha 16 (A14) LYS-->GLU]
      in a blood donor from the Acre State Blood Bank, in the Brazilian Amazon region.
      We confirmed the mutation by electrophoretic and chromatographic methods and by
      DNA sequencing. A literature search showed that this is the first description of
      this alpha globin mutant in a Brazilian Caucasian group. We also emphasize the
      importance of the hemoglobin study in blood donors for the purpose of the genetic
      counseling and quality assurance of the blood to be transfused. Screening tests
      for hemoglobin mutants are also important for gathering anthropological
      information about the Brazilian population.

PMID- 17183483
TI  - Phylogeography of Brachyplatystoma rousseauxii (Siluriformes - Pimelodidae) in
      the Amazon Basin offers preliminary evidence for the first case of "homing" for
      an Amazonian migratory catfish.
AB  - The large pimelodid, Brachyplatystoma rousseauxii, is one of the two most
      important catfish species for the fisheries in the Amazon. It is captured by
      commercial and artisanal fishing fleets in at least five Amazonian countries, at
      fishing grounds more than 5000 km apart. Current evidence suggests a complex life
      cycle that includes the longest reproductive migration known for a freshwater
      fish species. Experimental fisheries have pointed to a decrease in yield in the
      Western Amazon. However, reliable information about the capture and status of
      this fishery resource is still nonexistent, and no study has ever addressed its
      genetic diversity. We sequenced the entire D-loop of 45 individuals of B.
      rousseauxii, fifteen from each of three different fishing locations along the
      main channel of the Solimoes-Amazonas System covering a distance of around 2200
      km. Results of phylogenetic analyses, molecular diversity estimations, analysis
      of molecular variance, and nested clade analysis, together show that there is no
      genetic segregation associated with location in the main channel, as one would
      expect for a migratory species. However, the significant decrease found in
      genetic diversity towards the western part of the Amazon could be explained by a
      non-random choice of tributary to spawn. It is possible that the genetic
      diversity of the migrating schools decreases towards the west because portions of
      the species' genetic diversity are being "captured" by the different effluents,
      as the fish migrates to spawn in the headwaters. Like the salmon in North
      America, B. rousseauxii may be returning to their home tributary to spawn.

PMID- 17183482
TI  - The Star STING server: a multiplatform environment for protein structure
      analysis.
AB  - Star STING is the latest version of the STING suite of programs and corresponding
      database. We report on five important aspects of this package that have acquired
      some new characteristics, designed to add key advantages to the whole suite: 1)
      availability for most popular platforms and browsers, 2) introduction of the
      STING_DB quality assessment, 3) improvement in algorithms for calculation of
      three STING parameters, 4) introduction of five new STING modules, and 5)
      expansion of the existing modules. Star STING is freely accessible at:
      http://sms.cbi.cnptia.embrapa.br/SMS/, http://trantor.bioc.columbia.edu/SMS,
      http://www.es.embnet.org/SMS/, http://gibk26.bse.kyutech.ac.jp/SMS/ and
      http://www.ar.embnet.org/SMS.

PMID- 17183484
TI  - Comparison of simple sequence repeats in 19 Archaea.
AB  - All organisms that have been studied until now have been found to have
      differential distribution of simple sequence repeats (SSRs), with more SSRs in
      intergenic than in coding sequences. SSR distribution was investigated in Archaea
      genomes where complete chromosome sequences of 19 Archaea were analyzed with the
      program SPUTNIK to find di- to penta-nucleotide repeats. The number of repeats
      was determined for the complete chromosome sequences and for the coding and non
      coding sequences. Different from what has been found for other groups of
      organisms, there is an abundance of SSRs in coding regions of the genome of some
      Archaea. Dinucleotide repeats were rare and CG repeats were found in only two
      Archaea. In general, trinucleotide repeats are the most abundant SSR motifs;
      however, pentanucleotide repeats are abundant in some Archaea. Some of the
      tetranucleotide and pentanucleotide repeat motifs are organism specific. In
      general, repeats are short and CG-rich repeats are present in Archaea having a CG
      rich genome. Among the 19 Archaea, SSR density was not correlated with genome
      size or with optimum growth temperature. Pentanucleotide density had an inverse
      correlation with the CG content of the genome.

PMID- 17183485
TI  - Transcriptional regulation of catabolic pathways for aromatic compounds in
      Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum is a gram-positive soil microorganism able to utilize
      a large variety of aromatic compounds as the sole carbon source. The
      corresponding catabolic routes are associated with multiple ring-fission
      dioxygenases and among other channeling reactions, include the gentisate pathway,
      the protocatechuate and catechol branches of the beta-ketoadipate pathway and two
      potential hydroxyquinol pathways. Genes encoding the enzymatic machinery for the
      bioconversion of aromatic compounds are organized in several clusters in the C.
      glutamicum genome. Expression of the gene clusters is under specific
      transcriptional control, apparently including eight DNA-binding proteins
      belonging to the AraC, IclR, LuxR, PadR, and TetR families of transcriptional
      regulators. Expression of the gentisate pathway involved in the utilization of 3
      hydroxybenzoate and gentisate is positively regulated by an IclR-type activator.
      The metabolic channeling of ferulate, vanillin and vanillate into the
      protocatechuate branch of the beta-ketoadipate pathway is controlled by a PadR
      like repressor. Regulatory proteins of the IclR and LuxR families participate in
      transcriptional regulation of the branches of the beta-ketoadipate pathway that
      are involved in the utilization of benzoate, 4-hydroxybenzoate and
      protocatechuate. The channeling of phenol into this pathway may be under positive
      transcriptional control by an AraC-type activator. One of the potential
      hydroxyquinol pathways of C. glutamicum is apparently repressed by a TetR-type
      regulator. This global analysis revealed that transcriptional regulation of
      aromatic compound utilization is mainly controlled by single regulatory proteins
      sensing the presence of aromatic compounds, thus representing single input motifs
      within the transcriptional regulatory network of C. glutamicum.

PMID- 17183486
TI  - Responses to selection for milk traits in dairy buffaloes.
AB  - The aim of the present study was to estimate the index and individual responses
      to selection for milk (MY), fat (FY) and protein (PY) yields for different
      breeding goals for two commercial buffalo milk production systems in Sao Paulo
      State characterized by: 1) all milk produced is sold to the industry (MILK) and
      2) all milk produced is used in the mozzarella cheese-making process at the farm
      (MOZZARELLA). The current payment policy is based exclusively on milk volume. The
      mozzarella price refers to the wholesale selling price. Index responses to
      selection (IR) were calculated for three different breeding goals (BG): 1) MY
      exclusively (BG(1)); 2) FY + PY (BG(2)) and 3) MY + FY + PY (BG(3)). IR for the
      MILK system were 41.79 US dollars (BG(1)), 5.91 US dollars (BG(2)) and 38.22 US
      dollars (BG(3)). For the MOZZARELLA system, IR were 179.50 US dollars (BG(1)),
      262.85 US dollars (BG(2)) and 402.41 US dollars (BG(3)). The results suggest that
      for the present circumstances, selection for milk components is not advantageous
      when milk is produced for sale to the industry. However, when mozzarella making
      is added to the system, the selection for components and milk volume is the most
      economically beneficial.

PMID- 17183487
TI  - Evidence of allopolyploidy in Brachiaria brizantha (Poaceae: Paniceae) through
      chromosome arrangement at metaphase plate during microsporogenesis.
AB  - In the hexaploid (2n = 6x = 54) accession B176 of Brachiaria brizantha, one
      cytological characteristic differentiated it from the other accessions previously
      analyzed with the same ploidy level. Nearly 40% of meiocytes displayed the
      chromosome set arranged at two metaphase plates at the poles of the cell, close
      to the membrane. In these cells, both metaphase plates were arranged in an angle
      to form a typical tripolar spindle. Therefore, cells did not show normal
      chromosome segregation at anaphase I. Only nine univalent chromosomes migrated
      from each plate to the opposite pole with the remainder staying immobile on the
      plate. As a result of such spindle orientation and chromosome behavior,
      trinucleate telophases I were recorded. After telophase, cytokinesis eliminated
      the small nuclei into a microcyte. The second division proceeded normally, with
      the presence of microcytes in all phases. The origin of such an abnormality was
      explained on the hexaploid level of the accession which could have resulted by
      chromosome doubling of a triploid derived from species that did not display the
      same behavior for spindle organization. The high percentage of meiotic
      abnormalities recorded in this accession compromises fertility and renders it
      inadequate for the breeding program.

PMID- 17183488
TI  - Genetic variability in species of bats revealed by RAPD analysis.
AB  - Random amplified polymorphic DNA molecular marker was utilized as a means of
      analyzing genetic variability in seven bat species: Molossus molossus, M. rufus,
      Eumops glaucinus, E. perotis, Myotis nigricans, Eptesicus furinalis, and Artibeus
      planirostris. The determination of genetic diversity was based on 741 bands
      produced by a 20-random primer set. Only eight bands were considered monomorphic
      to one species. The greatest number of bands and the most polymorphic condition
      were exhibited by M. molossus, followed by M. nigricans, A. planirostris, E.
      furinalis, E. glaucinus, M. rufus, and E. perotis. Nei's genetic diversity index
      in the seven species considering the 20 primers was not greater than 0.22, but
      some primers were capable of detecting values between 0.39 and 0.49. Nei's
      unbiased genetic distance values and the UPGMA clustering pattern show that M.
      molossus and M. rufus have a close genetic relationship, unlike that observed
      between E. perotis and E. glaucinus. The latter was clustered with A.
      planirostris and E. furinalis. The low values for genetic diversity and distance
      observed indicate a genetic conservatism in the seven species. The fluorescent in
      situ hybridization experiments did not confirm a monomorphic condition for the
      eight bands identified, demonstrating that the monomorphic bands obtained by
      random amplified polymorphic DNA are insufficient for the identification of bat
      species.

PMID- 17183489
TI  - Protein thermostability in Archaea and Eubacteria.
AB  - In order to survive at high temperatures, thermophilic prokaryotes (Archaea and
      Eubacteria) adopt different strategies. Among several important contributing
      factors for stability of proteins are CG-rich codons, the ratio of charged amino
      acids compared to uncharged amino acids, ionic interactions, amino acid
      preferences and their distribution, post-translational modifications, and solute
      accumulation. However, these factors may differ from taxon to taxon, both within
      and between species depending upon the composition of proteins found in these
      organisms. This is exemplified in the case of differences in strategies adopted
      by soluble proteins and membrane proteins. Therefore, it appears that no single
      factor or combination of factors together can be universally attributed to the
      provision of thermal stability in proteins.

PMID- 17183490
TI  - Estimation of genetic parameters for a new model for defining body structure
      scores (frame scores) in Nellore cattle.
AB  - Models for estimation of frame scores in Nellore beef cattle (FRAME_GMA) were
      developed, comparing them with frame scores estimated using equations proposed by
      the Beef Improvement Federation (FRAME_BIF, USA). Correlation among frame scores
      obtained by these two methodologies, along with the independent variables
      considered in the estimation models, were also studied. A data set with 12,728
      animals, with ages between 490 and 610 days, was used. The models that best
      adjusted to FRAME_GMA included hip height, weight and interaction between height
      and weight. Estimates of heritability for FRAME_GMA and FRAME_BIF were 0.26 +/-
      0.03 and 0.23 +/- 0.03, respectively, in single trait analysis, and 0.28 and
      0.24, respectively, in multi-trait analysis. Phenotypic Pearson and Spearman
      correlation coefficients between FRAME_GMA and FRAME_BIF for males were 0.87 and
      0.83, respectively, being lower than those found for females (0.92 for both
      coefficients). Genetic correlation between the frame scores did not differ
      between genders, with values of 0.92 for the Pearson coefficient and 0.91 for the
      Spearman coefficient. We concluded that FRAME_GMA was better adapted to this data
      set than FRAME_BIF. Other studies need to be made to evaluate the applicability
      of this proposed model to other populations of Nellore beef cattle and for other
      age groups.

PMID- 17183491
TI  - Microsporogenesis in Brachiaria dictyoneura (Fig. & De Not.) Stapf (Poaceae:
      Paniceae).
AB  - Microsporogenesis was analyzed in five accessions of Brachiaria dictyoneura
      presenting x = 6 as the basic chromosome number. All accessions were tetraploid
      (2n = 4x = 24) with chromosome pairing in bi-, tri-, and quadrivalents. The
      recorded meiotic abnormalities were those typical of polyploids, including
      precocious chromosome migration to the poles, laggard chromosomes, and
      micronucleus formation. The frequency of these abnormalities, however, was lower
      than those reported for other polyploid accessions previously analyzed for other
      Brachiaria species. Cell fusion and absence of cytokinesis were also recorded in
      some accessions, leading to restitutional nucleus formation in some cells.
      Genetically unbalanced microspores, binucleate, and 2n microspores were found
      among normal meiotic products as results from these abnormalities. The limitation
      in using these accessions as pollen donor in interspecific crosses with sexual
      species with x = 7 or x = 9 in breeding programs is discussed.

PMID- 17183492
TI  - Transferability of short tandem repeat markers for two wild Canid species
      inhabiting the Brazilian Cerrado.
AB  - The maned wolf (Chrysocyon brachyurus) and the crab-eating fox (Cerdocyon thous)
      are two wild-canid species found in the Brazilian Cerrado. We tested cross
      amplification and transferability of 29 short tandem repeat primers originally
      developed for cattle and domestic dogs and cats on 38 individuals of each of
      these two species, collected in the Emas National Park, which is the largest
      national park in the Cerrado region. Six of these primers were successfully
      transferred (CSSM-038, PEZ-05, PEZ-12, LOCO-13, LOCO-15, and PEZ-20); five of
      which were found to be polymorphic. Genetic parameter values (number of alleles
      per locus, observed and expected heterozygosities, and fixation indices) were
      within the expected range reported for canid populations worldwide.

PMID- 17183493
TI  - Rapid and efficient protocol for DNA extraction and molecular identification of
      the basidiomycete Crinipellis perniciosa.
AB  - DNA isolation from some fungal organisms is difficult because they have cell
      walls or capsules that are relatively unsusceptible to lysis. Beginning with a
      yeast Saccharomyces cerevisiae genomic DNA isolation method, we developed a 30
      min DNA isolation protocol for filamentous fungi by combining cell wall digestion
      with cell disruption by glass beads. High-quality DNA was isolated with good
      yield from the hyphae of Crinipellis perniciosa, which causes witches' broom
      disease in cacao, from three other filamentous fungi, Lentinus edodes, Agaricus
      blazei, Trichoderma stromaticum, and from the yeast S. cerevisiae. Genomic DNA
      was suitable for PCR of specific actin primers of C. perniciosa, allowing it to
      be differentiated from fungal contaminants, including its natural competitor, T.
      stromaticum.

PMID- 17183494
TI  - Personalized diagnosis by cached solutions with hypertension as a study model.
AB  - Statistical modeling of links between genetic profiles with environmental and
      clinical data to aid in medical diagnosis is a challenge. Here, we present a
      computational approach for rapidly selecting important clinical data to assist in
      medical decisions based on personalized genetic profiles. What could take hours
      or days of computing is available on-the-fly, making this strategy feasible to
      implement as a routine without demanding great computing power. The key to
      rapidly obtaining an optimal/nearly optimal mathematical function that can
      evaluate the "disease stage" by combining information of genetic profiles with
      personal clinical data is done by querying a precomputed solution database. The
      database is previously generated by a new hybrid feature selection method that
      makes use of support vector machines, recursive feature elimination and random
      sub-space search. Here, to evaluate the method, data from polymorphisms in the
      renin-angiotensin-aldosterone system genes together with clinical data were
      obtained from patients with hypertension and control subjects. The disease "risk"
      was determined by classifying the patients' data with a support vector machine
      model based on the optimized feature; then measuring the Euclidean distance to
      the hyperplane decision function. Our results showed the association of renin
      angiotensin-aldosterone system gene haplotypes with hypertension. The association
      of polymorphism patterns with different ethnic groups was also tracked by the
      feature selection process. A demonstration of this method is also available
      online on the project's web site.

PMID- 17183495
TI  - Countercurrent laminar microflow for highly efficient solvent extraction.

PMID- 17183496
TI  - Heterogeneous asymmetric catalysis with homochiral metal-organic frameworks:
      network-structure-dependent catalytic activity.

PMID- 17183497
TI  - Photomechanical effects of ferroelectric liquid-crystalline elastomers containing
      azobenzene chromophores.

PMID- 17183498
TI  - A flexible porous coordination polymer functionalized by unsaturated metal
      clusters.

PMID- 17183499
TI  - A solid-phase route to 18F-labeled tracers, exemplified by the synthesis of
      [18F]2-Fluoro-2-deoxy-D-glucose.

PMID- 17183500
TI  - A bridging double bond as an electron acceptor for optical nonlinearity of furan
      containing [N.2]cyclophenes.

PMID- 17183501
TI  - Variable synthesis of the optically active thiotetronic acid antibiotics
      thiolactomycin, thiotetromycin, and 834-B1.

PMID- 17183502
TI  - Formation of mesoporous carbon with a face-centered-cubic Fd3$m structure and
      bimodal architectural pores from the reverse amphiphilic triblock copolymer PPO
      PEO-PPO.

PMID- 17183503
TI  - Decolourisation of a synthetic textile effluent using a bacterial consortium.
AB  - In the present study we examined the performance of a thermoalkalophilic
      bacterial consortium, where the predominant strain was Bacillus sp. SF, in the
      degradation of Reactive Black 5 (RB5). We used a reactor working in continuous
      mode and investigated the effects of pH, hydraulic retention time (HRT) and
      several added salts on colour and chemical oxygen demand (COD) reductions. For
      the chosen operational conditions (pH 9, 55 degrees C and HRT of 12 h) the
      efficiencies achieved were 91.2 +/- 0.8 % for colour removal and 81.2% for COD
      removal. The system tolerated, with no significant decrease in colour removal
      efficiency, 30 g/L Na(2)SO(4), Na(2)CO(3) or NaCl. The latter two salts, however,
      led to a reduction in COD removal of 30% and 50%, respectively. The system proved
      to be very effective in the decolourisation of C.I. RB5 under alkaline conditions
      and at a comparatively high temperature.

PMID- 17183504
TI  - Demethyloleuropein and beta-glucosidase activity in olive fruits.
AB  - Demethyloleuropein plays a major role in the defense mechanism of olive fruits.
      To understand how this molecule is metabolized during different stages of
      maturation of olive fruits, a biomolecular approach to identify the
      demethyloleuropein chemistry was employed. The beta-glucosidase activity in crude
      extracts was assayed spectrophotometrically using the chromogenic substrate p
      nitrophenyl-beta-D-glucopyranoside. Demethyloleuropein was extracted and
      identified by HPLC-MS from both infected and uninfected olive fruits at different
      physiological stages. The release of more functionally relevant dialdehydes in
      uninfected fruits was investigated using ESIMS/ MS. In fruits harvested in
      October, the activity of beta-glucosidase was significantly enhanced in
      uninfected fruits when compared to the infected fruits. Quantitative differences
      in the demethyloleuropein content from uninfected fruits showed the highest
      values (5.09 mg/g) in October, whereas lower levels (4.44 mg/g) were found in
      infected fruits. The results demonstrated that demethyloleuropein derivatives
      could be influenced by beta-glucosidase activity to improve the quality of the
      olive products with the best dialdehyde nutraceutical content.

PMID- 17183505
TI  - Biomolecular computing: is it ready to take off?
AB  - Biomolecular computing is an emerging field at the interface of computer science,
      biological science and engineering. It uses DNA and other biological materials as
      the building blocks for construction of living computational machines to solve
      difficult combinatorial problems. In this article, notable advances in the
      biomolecular computing are reviewed and challenges associated with this
      multidisciplinary research are addressed. Finally, several perspectives are given
      based on the review of biomolecular computing.

PMID- 17183506
TI  - Better library design: data-driven protein engineering.
AB  - Data-driven protein engineering is increasingly used as an alternative to
      rational design and combinatorial engineering because it uses available knowledge
      to limit library size, while still allowing for the identification of
      unpredictable substitutions that lead to large effects. Recent advances in
      computational modeling and bioinformatics, as well as an increasing databank of
      experiments on functional variants, have led to new strategies to choose
      particular amino acid residues to vary in order to increase the chances of
      obtaining a variant protein with the desired property. Strategies for limiting
      diversity at each position, design of small sub-libraries, and the performance of
      scouting experiments, have also been developed or even automated, further
      reducing the library size.

PMID- 17183507
TI  - Recent progress in engineering alpha/beta hydrolase-fold family members.
AB  - The members of the alpha/beta hydrolase-fold family represent a functionally
      versatile group of enzymes with many important applications in biocatalysis.
      Given the technical significance of alpha/beta hydrolases in processes ranging
      from the kinetic resolution of enantiomeric precursors for pharmaceutical
      compounds to bulk products such as laundry detergent, optimizing and tailoring
      enzymes for these applications presents an ongoing challenge to chemists,
      biochemists, and engineers alike. A review of the recent literature on alpha/beta
      hydrolase engineering suggests that the early successes of "random processes"
      such as directed evolution are now being slowly replaced by more hypothesis
      driven, focused library approaches. These developments reflect a better
      understanding of the enzymes' structure-function relationship and improved
      computational resources, which allow for more sophisticated search and prediction
      algorithms, as well as, in a very practical sense, the realization that bigger is
      not always better.

PMID- 17183508
TI  - One-step purification of Taq DNA polymerase using nucleotide-mimetic affinity
      chromatography.
AB  - The thermostable Thermus aquaticus DNA polymerase (Taq Pol) has been the key
      factor in transforming the initial PCR method into one with huge impact in
      molecular biology and biotechnology. Therefore, the development of effective
      affinity adsorbents for the purification of Taq Pol, as well as other DNA
      polymerases, attracts the attention of the enzyme manufacturers and the research
      laboratories. In this report we describe a simple protocol for the purification
      of Taq Pol from E. coli lysates, leading to enzymes of high specific activity and
      purity. The protocol is based on a single affinity chromatography step, featuring
      an immobilized ligand selected from a structure-biased combinatorial library of
      dNTP-mimetic synthetic ligands. The ligand library was screened for its ability
      to bind and purify Taq Pol from E. coli lysates. One immobilized ligand (mABSGu)
      of the general formula X-Trz-Y, bearing 9-aminoethylguanine (AEGu) and aniline-2
      sulfonic acid (mABS) linked on the triazine scaffold (Trz), displayed the highest
      purifying ability. Adsorption equilibrium studies with this affinity ligand and
      Taq Pol determined a dissociation constant (KD) of 0.12 mM for the respective
      complex, whereas ATP prevented the formation of the mABSGu-Taq Pol complex. The
      mABSGu affinity adsorbent was exploited in the development of a facile Taq Pol
      purification protocol, affording homogeneous enzyme (>99% purity, approximately
      61 500 U/mg) in a single chromatography step. Quality control tests showed that
      Taq Pol purified on the mABSGu affinity adsorbent is free of nucleic acids and
      contaminating nuclease activities.

PMID- 17183510
TI  - Are transversion mutations better? A Mutagenesis Assistant Program analysis on
      P450 BM-3 heme domain.
AB  - Directed evolution represents a versatile tool to tailor enzyme properties to
      needs in industrial applications and to understand structure-function
      relationships. Genetic diversity is commonly generated using error-prone PCR.
      Exploration of sequence space by random mutagenesis strongly favors transitions
      when enzyme-based mutagenesis methods are employed (Wong, T. S., Zhurina, D.,
      Schwaneberg, U., Comb. Chem. High Throughput Screen. 2006, 9, 271-288). The
      genetic code has been organized in a manner that limits chemical diversity when a
      single transition mutation occurs in a codon (Wong, T. S., Roccatano, D.,
      Schwaneberg, U., Biocatal. Biotransformation 2006, in press). Are transitions
      more beneficial than transversions for adapting biocatalysts to non-natural
      process conditions? In a statistical analysis performed with the Mutagenesis
      Assistant Program (MAP), we compared the consequences of transition and
      transversion bias on amino acid substitution patterns of the P450 BM-3 heme
      domain. For the analysis, we used a recently introduced benchmarking system
      consisting of a protein structure indicator, an amino acid diversity indicator
      with a codon diversity coefficient, and a chemical diversity indicator. A
      detailed analysis for the P450 BM-3 heme domain showed that an ideal transversion
      bias generates more diverse amino acid substitution patterns with a significantly
      different chemical composition than an ideal transition bias. Emphasis is given
      on the theoretical analysis with a brief discussion on potential implication of
      transition and transversion bias in directed evolution experiments.

PMID- 17183509
TI  - Expression of an acetyl-CoA synthase and a CoA-transferase in Escherichia coli to
      produce modified taxanes in vivo.
AB  - Previous in vitro studies revealed that the 10-deacetylbaccatin III 10beta-O
      acetyltransferase (DBAT) from Taxus can catalyze the transfer of acetyl,
      propionyl or n-butyryl from CoA to the C10-hydroxyl of 10-deacetylbaccatin III.
      Accordingly, Escherichia coli JM109 were transformed to recombinantly express
      dbat, and this enzyme function was coupled to that of acetyl-CoA synthase (acs,
      EC 6.2.1.1) expressed from and regulated by genes encoded on the bacterial
      chromosome. Incubation of the bacteria with 10-deacetylbaccatin III and
      increasing concentrations of acetic acid revealed an in vivo conversion (
      approximately 10%) of substrate to natural product baccatin III (C10-acetylated),
      which was remarkably similar to the relative conversion without acid
      supplementation. Incubation of the modified E. coli with 5 mM propionic acid,
      revealed a fivefold increase in the conversion ( approximately 13%) of 10
      deacetylbaccatin III to 10-deacetyl-10-propionylbaccatin III, compared to
      approximately 2% conversion in the absence of exogenous propionate. To produce
      the butyrylbaccatin III analog in vivo, bacteria were engineered to co-express
      the dbat and atoAD (EC 2.8.3.8) genes; the latter encodes an acetoacetate: acetyl
      CoA CoA-transferase that activates butyrate to butyryl CoA. The bacteria were
      incubated with 10-deacetylbaccatin III and 25-100 mM butyrate, and a maximum of
      approximately 2.6% conversion to 10-butyrylbaccatin III was observed compared to
      approximately 0.6% conversion when no exogenous butyrate was supplied.

PMID- 17183512
TI  - A prospective pilot study of a multidisciplinary home training programme for
      lateral epicondylitis.
AB  - OBJECTIVE: To evaluate a new multidisciplinary structured home training programme
      for patients with lateral epicondylitis compared to conventional attendance.
      DESIGN: This study utilized a prospective non-randomized design to compare the
      effect of a home exercise programme against a pragmatic approach to managing
      patients with lateral epicondylitis in a primary care setting in Sweden.
      SUBJECTS: A total of 78 patients, presenting to their general practitioner with
      lateral epicondylitis were recruited from two separate geographical areas. The
      patients were divided into two group, 51 entered the intervention group and 27
      entered the control group. METHODS: The intervention group was treated with a
      specific home training programme, ergonomic advice and when necessary wrist
      and/or night bandages. The control group was treated with conventional treatment,
      e.g. corticosteroid injections, stretching or no intervention. Pain and function
      were evaluated by the PRFEQ. An electronic hand-power gauge measured strength and
      stamina. Sick-leave absence was collected via the regional Social Insurance
      Office. RESULTS: After four weeks the intervention group experienced less sick
      leave, less pain, better function and returned to work earlier than the control
      group. After 16 weeks the intervention group still had significantly better
      function than the control group and were taking less sick-leave. Pain decreased
      more in the intervention group but this was not significant. There was no
      difference in grip strength between the two groups. CONCLUSION: A structured home
      training programme can improve function and reduce sick leave in patients with
      lateral epicondylitis.

PMID- 17183511
TI  - Identification of tunnels in proteins, nucleic acids, inorganic materials and
      molecular ensembles.
AB  - The knowledge of the access paths connecting interior of molecular systems with
      surrounding environment is important for the understanding of structurefunction
      relationships and engineering of molecules for biotechnological applications.
      CAVER is a computer program developed for calculations of tunnels, channels or
      pores in the biomolecules, inorganic materials and molecular ensembles. The
      algorithm performs a skeleton search based on a reciprocal distance function
      grid. The algorithm is implemented in the stand-alone version, web version and as
      plug-in for PyMol. CAVER is available from the website
      http://loschmidt.chemi.muni.cz/caver.

PMID- 17183513
TI  - Biological and structural characterization of new linear gomesin analogues with
      improved therapeutic indices.
AB  - Gomesin (Gm) is a potent antimicrobial peptide isolated from the spider
      Acanthoscurria gomesiana. The two disulfide bridges Cys(2,15) and Cys(6,11)
      facilitate the folding of the molecule in a beta-hairpin structure, conferring on
      the peptide a high stability in human plasma. We report herein biological and
      structural features of new linear Gm analogues, obtained by combining the removal
      of both disulfide bridges and the incorporation of a D- or L-proline. Regarding
      their biological properties, two analogues, namely, [D-Thr(2,6,11,15), Pro(9)]-D
      Gm and [Thr(2,6,11,15), D-Pro(9)]-Gm, are as potent as Gm against Candida
      albicans and only fourfold less against Staphylococcus aureus and Escherichia
      coli. In addition, at 100 microM they are approximately threefold less hemolytic
      than Gm. The best therapeutic indices were found for [D-Thr(2,6,11,15), Pro(9)]-D
      Gm and for [(Des-pGlu(1), -Thr(2), -Arg(3)), Thr(6,11,15), D-Pro(9)]-Gm with a 32
      fold increase of their activity against bacteria, and from 128- to 512-fold
      against yeast when compared with Gm. Regarding the stability, [D-Thr(2,6,11,15),
      Pro(9)]-D-Gm appeared to be the most resistant in human serum, along with [D
      Thr(2,6,11,15), Pro(8)]-D-Gm and [Thr(2,6,11,15), D-Arg(4,16), D-Pro(9)]-Gm. When
      evaluating their conformation by CD spectroscopy in sodium dodecyl sulfate (SDS),
      most linear analogues display beta-conformation characteristics. Moreover,
      considering its high therapeutic index and stability in serum, [D-Thr(2,6,11,15),
      Pro(9)]-D-Gm was further analyzed by NMR spectroscopy. (1)H NMR experiments in
      SDS micelles demonstrated that [D-Thr(2,6,11,15), Pro(9)]-D-Gm presents a
      conformation very similar to that of Gm. In our search for Gm analogues with
      enhanced potential for drug development, we demonstrated that designing cysteine
      free analogues can improve the therapeutic index of Gm derivatives.

PMID- 17183514
TI  - Molecular chemical structure of barley proteins revealed by ultra-spatially
      resolved synchrotron light sourced FTIR microspectroscopy: comparison of barley
      varieties.
AB  - Barley protein structure affects the barley quality, fermentation, and
      degradation behavior in both humans and animals among other factors such as
      protein matrix. Publications show various biological differences among barley
      varieties such as Valier and Harrington, which have significantly different
      degradation behaviors. The objectives of this study were to reveal the molecular
      structure of barley protein, comparing various varieties (Dolly, Valier,
      Harrington, LP955, AC Metcalfe, and Sisler), and quantify protein structure
      profiles using Gaussian and Lorentzian methods of multi-component peak modeling
      by using the ultra-spatially resolved synchrotron light sourced Fourier transform
      infrared microspectroscopy (SFTIRM). The items of the protein molecular structure
      revealed included protein structure alpha-helices, beta-sheets, and others such
      as beta-turns and random coils. The experiment was performed at the National
      Synchrotron Light Source in Brookhaven National Laboratory (BNL, US Department of
      Energy, NY). The results showed that with the SFTIRM, the molecular structure of
      barley protein could be revealed. Barley protein structures exhibited significant
      differences among the varieties in terms of proportion and ratio of model-fitted
      alpha-helices, beta-sheets, and others. By using multi-component peaks modeling
      at protein amide I region of 1710-1576 cm-1, the results show that barley protein
      consisted of approximately 18-34% of alpha-helices, 14-25% of beta-sheets, and 44
      69% others. AC Metcalfe, Sisler, and LP955 consisted of higher (P<0.05)
      proportions of alpha-helices (30-34%) than Dolly and Valier (alpha-helices 18
      23%). Harrington was in between which was 25%. For protein beta-sheets, AC
      Metcalfe, and LP955 consisted of higher proportions (22-25%) than Dolly and
      Valier (13-17%). Different barley varieties contained different alpha-helix to
      beta-sheet ratios, ranging from 1.4 to 2.0, although the difference were
      insignificant (P>0.05). The ratio of alpha-helices to others (0.3 to 1.0, P<0.05)
      and that of beta-sheets to others (0.2 to 0.8, P<0.05) were different among the
      barley varieties. It needs to be pointed out that using a multi-peak modeling for
      protein structure analysis is only for making relative estimates and not exact
      determinations and only for the comparison purpose between varieties. The
      principal component analysis showed that protein amide I Fourier self
      deconvolution spectra were different among the barley varieties, indicating that
      protein internal molecular structure differed. The above results demonstrate the
      potential of the SFTIRM to localize relatively pure protein areas in barley
      tissues and reveal protein molecular structure. The results indicated relative
      differences in protein structures among the barley varieties, which may partly
      explain the biological differences among the barley varieties. Further study is
      needed to understand the relationship between barley molecular chemical structure
      and biological features in terms of nutrient availability and digestive behavior.

PMID- 17183515
TI  - Effect of osteonectin-derived peptide on the viscoelasticity of hydrogel/apatite
      nanocomposite scaffolds.
AB  - Hydrogel/apatite nanocomposites are the ideal biomaterial to mimic the physio
      chemical and biologic properties of the bone and to fabricate scaffolds for bone
      regeneration. The objective of this work was to investigate the effect of an
      osteonectin derived glutamic acid sequence on the viscoelastic properties of
      poly(lactide-ethylene oxide-fumarate) (PLEOF)/apatite composite, as a model
      degradable material in bone regeneration. Osteonectin is an extracellular acidic
      glycoprotein of the bone matrix, which is believed to be involved in linking the
      collagen network to hydroxyapatite (HA), the mineral phase of the bone. We
      synthesized a 6-glutamic acid sequence in solid phase with affinity to HA
      crystals via ionic interactions. One end of the synthesized peptide was
      functionalized with an acrylate group to covalently attach the peptide (Ac-Glu6)
      to the aqueous-based biodegradable and in situ crosslinkable PLEOF hydrogel
      matrix. To determine the effect of energetic interactions between the fillers and
      hydrogel matrix, HA nanoparticles were also treated with an acrylate
      functionalized 6-glycine amino acid peptide (Ac-Gly6) that interacts with the
      fillers only by van der Waals and polar interactions (without ionic
      interactions). Crosslinked PLEOF/apatite scaffolds were prepared using PLEOF as
      the degradable macromer, HA nanofillers treated with Ac-Glu6 peptide linker, and
      a neutral redox initiation system. The viscoelastic properties were studied by
      dynamic time sweep, strain sweep, and small amplitude oscillatory rheometry.
      Composites without surface treatment, treated with Ac-Gly6, and treated with Ac
      Glu6 at different volume fractions and various particle sizes were examined. The
      results showed that the 6-mer glutamic acid sequence significantly affects the
      shear modulus of the scaffold because of ionic interactions between the peptide
      and HA crystals.

PMID- 17183516
TI  - Cyclic [5]paraphenyleneacetylene: synthesis, properties, and formation of a ring
      in-ring complex showing a considerably large association constant and entropy
      effect.

PMID- 17183517
TI  - Differential analysis of 2D NMR spectra: new natural products from a pilot-scale
      fungal extract library.

PMID- 17183518
TI  - Molecular 2:1 digital multiplexer.

PMID- 17183520
TI  - Crystal structures of and displacive transitions in OsN2, IrN2, RuN2, and RhN2.

PMID- 17183519
TI  - Azide-analogous organophosphorus chemistry: RNP2 as a ligand and P2 source.

PMID- 17183521
TI  - Hyrtiosal, a PTP1B inhibitor from the marine sponge Hyrtios erectus, shows
      extensive cellular effects on PI3K/AKT activation, glucose transport, and
      TGFbeta/Smad2 signaling.
AB  - Protein tyrosine phosphatase 1B (PTP1B) negatively regulates insulin signaling,
      and PTP1B inhibitors have been seen as promising therapeutic agents against
      obesity and type 2 diabetes. Here we report that the marine natural product
      hyrtiosal, from the marine sponge Hyrtios erectus, has been discovered to act as
      a PTP1B inhibitor and to show extensive cellular effects on PI3K/AKT activation,
      glucose transport, and TGFbeta/Smad2 signaling. This inhibitor wad able to
      inhibit PTP1B activity in dose-dependent fashion, with an IC(50) value of 42
      microM in a noncompetitive inhibition mode. Further study with an IN Cell
      Analyzer 1000 cellular fluorescence imaging instrument showed that hyrtiosal
      displayed potent activity in abolishing the retardation of AKT membrane
      translocation caused by PTP1B overexpression in CHO cells. Moreover, it was found
      that this newly identified PTP1B inhibitor could dramatically enhance the
      membrane translocation of the key glucose transporter Glut4 in PTP1B
      overexpressed CHO cells. Additionally, in view of our recent finding that PTP1B
      was able to modulate insulin-mediated inhibition of Smad2 activation, hyrtiosal
      was also tested for its capabilities in the regulation of Smad2 activity through
      the PI3K/AKT pathway. The results showed that hyrtiosal could effectively
      facilitate insulin inhibition of Smad2 activation. Our current study is expected
      to supply new clues for the discovery of PTP1B inhibitors from marine natural
      products, while the newly identified PTP1B inhibitor hyrtiosal might serve as a
      potential lead compound for further research.

PMID- 17183522
TI  - Nitrosation of N-terminally blocked tryptophan and tryptophan-containing peptides
      by peroxynitrite.
AB  - Tryptophan is known to be a major target of oxidative stress and to take part in
      electron transfer. In proteins, its fluorescence is extinguished after treatment
      with oxidative agents, like peroxynitrite (ONOO(-)/ONOOH) - the product of the
      reaction of NO* and superoxide anion (O*(2)(-)) radicals. The main reactions of N
      blocked tryptophan derivatives (melatonin or N-acetyl-L-tryptophan) exposed to
      peroxynitrite at physiological pH are oxidation to formylkynuramine or
      formylkynurenine, respectively, and nitrosation, which leads to substituted 1
      nitrosoindoles. Here we show that peroxynitrite-induced nitrosation is specific
      to N-blocked L-tryptophan derivatives and is not obtained with free L-tryptophan.
      Such a nitrosation can be evaluated by using 4,5-diaminofluorescein (DAF-2),
      which is converted to the fluorescent triazolofluorescein by NO* donors and
      nitrosating agents. N-acetyl-L-tryptophan was shown to be twice as efficient as
      melatonin in transferring NO from peroxynitrite to DAF-2. DAF-2 responses were
      then used to assess the ability of a series of L-tryptophan-containing peptides
      to give transient N-nitrosoindoles upon treatment with peroxynitrite. Many
      peptides proved not to be susceptible to nitrosation under these conditions.
      However, the N-terminally blocked peptide of endothelin-1 (Ac-Asp-Ile-Ile-Trp)
      reacted in a very similar fashion to melatonin; this shows that tryptophan
      residue nitrosation could occur when it was exposed to peroxynitrite.

PMID- 17183523
TI  - A structure-activity guided strategy for fluorescent labeling of annonaceous
      acetogenin mimetics and their application in cell biology.

PMID- 17183524
TI  - A novel methodological approach for the analysis of host-ligand interactions.
AB  - Traditional analysis of drug-binding data relies upon the Scatchard formalism.
      These methods rely upon the fitting of a linear equation providing intercept and
      gradient data that relate to physical properties, such as the binding constant,
      cooperativity coefficients and number of binding sites. However, the existence of
      different binding modes with different binding constants makes the implementation
      of these models difficult. This article describes a novel approach to the binding
      model of host-ligand interactions by using a derived analytical function
      describing the observed signal. The benefit of this method is that physically
      significant parameters, that is, binding constants and number of binding sites,
      are automatically derived by the use of a minimisation routine. This methodology
      was utilised to analyse the interactions between a novel antitumour agent and
      DNA. An optical spectroscopy study confirms that the pentacyclic acridine
      derivative (DH208) binds to nucleic acids. Two binding modes can be identified: a
      stronger one that involves intercalation and a weaker one that involves oriented
      outer-sphere binding. In both cases the plane of the bound acridine ring is
      parallel to the nucleic acid bases, orthogonal to the phosphate backbone.
      Ultraviolet (UV) and circular dichroism (CD) data were fitted using the proposed
      model. The binding constants and the number of binding sites derived from the
      model remained consistent across the different techniques used. The different
      wavelengths at which the measurements were made maintained the coherence of the
      results.

PMID- 17183525
TI  - Toward separation of nuclear spin isomers with coherent light.
AB  - We propose an approach for separating nuclear spin isomers with coherent light
      and illustrate it by numerical calculations using fulvene as a model system. The
      scheme employs the equivalence of torsion and interchange of equivalent H-atoms
      in a class of molecules of which fulvene is a simple example. The exchange
      symmetry couples with the rotational symmetry to produce a spatial distinction
      between the two photo-excited nuclear spin isomers, and wavepacket interferometry
      is applied to separate the species.

PMID- 17183526
TI  - From cloudy to transparent: chain rearrangement in hydrogen-bonded layer-by-layer
      assembled films.
AB  - The cloudiness of hydrogen-bonded LBL films assembled from polyvinylpyrrolidone
      (PVPON) and poly(acrylic acid) (PAA) is studied in detail by two approaches:
      spectroscopy (Fabry-Perot fringes) and microscopy (AFM). Fabrication parameters
      such as temperature, molecular weight, pH value, and rinsing time, have notable
      influences on film cloudiness. The buildup of the PVPON/ PAA film is a two-stage
      process of adsorption and chain rearrangement. Generally, adsorption is fast,
      while chain rearrangement is slow. The fast adsorption process traps defects,
      whereas the relatively slow chain-rearrangement process can not heal the defects
      in time; therefore; the number of defects continuously increases as LBL assembly
      proceeds, and a cloudy, heterogeneous film is produced. However, the as-prepared
      cloudy films become transparent and homogeneous on subsequent annealing in acidic
      water. UV/Vis spectroscopy and fluid AFM were applied to monitor this transition
      ex situ and in situ, respectively. It is found that increasing the annealing
      temperature accelerates the transition from cloudy to transparent, and the
      transition of the film made from higher molecular weight polymer is slower.

PMID- 17183527
TI  - Myocardin-related transcription factor B is required for normal mouse vascular
      development and smooth muscle gene expression.
AB  - Smooth muscle gene expression is required for the proper development and function
      of multiple organ systems. Expression of smooth muscle genes is critical for
      contractile function and tissue architectural integrity. One critical
      transcription factor for smooth muscle gene expression is the Serum Response
      Factor (SRF). SRF is expressed ubiquitously, but tissue-specific transcriptional
      regulation is conferred by its binding to cofactors such as myocardin. Myocardin
      related transcription factor B (MRTF-B) is a member of a family of genes
      (Myocardin(Myocd),Myocardin-related transcription factor A(MRTF-A),MRTF-B) that
      provides tissue-specificity and potentiate SRF-dependent transcription. Unlike
      myocardin, which is expressed specifically in smooth and cardiac muscle, MRTF-B
      is expressed in a wide variety of tissues. To examine the function of MRTF-B, we
      generated mice containing an insertional mutation of MRTF-B. MRTF-B homozygous
      mutants die in late gestation with vascular defects and liver hemorrhage. At
      E9.5, MRTF-B is expressed strongly in the septum transversum mesoderm critical
      for development of the vitelline system that produces the liver sinusoids and
      portal venous system. MRTF-B deficiency results in defective smooth muscle gene
      expression in the liver sinusoids, vitelline veins, and yolk sac, which
      contributes significantly to the lethal phenotype. These data support our
      hypothesis that MRTF-B has a unique role in regulating smooth muscle genes
      important for liver, yolk sac, and portal vascular development.

PMID- 17183528
TI  - Migratory patterns and developmental potential of trunk neural crest cells in the
      axolotl embryo.
AB  - Using cell markers and grafting, we examined the timing of migration and
      developmental potential of trunk neural crest cells in axolotl. No obvious
      differences in pathway choice were noted for DiI-labeling at different lateral or
      medial positions of the trunk neural folds in neurulae, which contributed not
      only to neural crest but also to Rohon-Beard neurons. Labeling wild-type dorsal
      trunks at pre- and early-migratory stages revealed that individual neural crest
      cells migrate away from the neural tube along two main routes: first,
      dorsolaterally between the epidermis and somites and, later, ventromedially
      between the somites and neural tube/notochord. Dorsolaterally migrating crest
      primarily forms pigment cells, with those from anterior (but not mid or
      posterior) trunk neural folds also contributing glia and neurons to the lateral
      line. White mutants have impaired dorsolateral but normal ventromedial migration.
      At late migratory stages, most labeled cells move along the ventromedial pathway
      or into the dorsal fin. Contrasting with other anamniotes, axolotl has a minor
      neural crest contribution to the dorsal fin, most of which arises from the
      dermomyotome. Taken together, the results reveal stereotypic migration and
      differentiation of neural crest cells in axolotl that differ from other
      vertebrates in timing of entry onto the dorsolateral pathway and extent of
      contribution to some derivatives.

PMID- 17183529
TI  - Roles of learning and motivation in preference behavior: mediation by entorhinal
      cortex, dorsal and ventral hippocampus.
AB  - In the latent cue preference (LCP) task, water-deprived rats alternately drink a
      salt solution in one distinctive compartment of a conditioned cue preference
      (CCP) apparatus and water in the other compartment over 8 days (training trials).
      They are then given a choice between the two compartments with no solutions
      present (preference test). Previous findings showed that this training procedure
      results in two parallel forms of learning: conditioning to water-paired cues (a
      water-CCP) and latent learning of an association between salt and salt-paired
      compartment cues (a salt-LCP). Experiment 1 examined these two types of learning
      in isolation. Results showed that expression of the salt-LCP required salt
      deprivation during testing, but expression of the water-CCP did not require a
      deprivation state during testing. Other results showed that salt-LCP learning
      itself involves two distinct components: (1) the latent association among neutral
      cues in the salt-paired compartment, and (2) motivational information about salt
      deprivation during testing. Previous findings also demonstrated roles for the
      dorsal hippocampus (DH), ventral hippocampus (VH), and entorhinal cortex (EC) in
      salt-LCP learning. Experiment 2 examined the involvement of these structures
      during acquisition or expression of salt-LCP learning. Rats with cannulas aimed
      at DH, VH, or EC were given infusions of muscimol, either before exposure to the
      salt-paired, but not the water-paired, compartment during training or before the
      preference test. Inactivation of the DH or EC impaired both acquisition and
      expression of the association between salt and salt-paired compartment cues,
      while inactivation of the VH disrupted the influence of motivational information
      about salt deprivation required to express the salt-LCP. These results suggest
      unique roles for the EC-DH circuit and VH in salt-LCP learning, as well as a
      functional dissociation between the DH and VH.

PMID- 17183530
TI  - Heparan sulfate Ndst1 gene function variably regulates multiple signaling
      pathways during mouse development.
AB  - Disruption of heparan sulfate (HS) synthesis in vertebrate development causes
      malformations that are composites of those caused by mutations of multiple HS
      binding growth factors and morphogens. We previously reported severe
      developmental defects of the forebrain and the skull in mutant mice bearing a
      targeted disruption of the heparan sulfate-generating enzyme GlcNAc N
      deacetylase/GlcN N-sulfotransferase 1 (Ndst1). Here, we further characterize the
      molecular mechanisms leading to frontonasal dysplasia in Ndst1 mutant embryos and
      describe additional malformations, including impaired spinal and cranial neural
      tube fusion and skeletal abnormalities. Of the numerous proteins that bind HS, we
      show that impaired fibroblast growth factor, Hedgehog, and Wnt function may
      contribute to some of these phenotypes. Our findings, therefore, suggest that
      defects in HS synthesis may contribute to multifactor types of congenital
      developmental defects in humans, including neural tube defects.

PMID- 17183531
TI  - Spatial selectivity and theta phase precession in CA1 interneurons.
AB  - Traditionally, most of the information processing of neural networks is thought
      to be carried out by excitatory cells. Likewise, recent evidence for temporal
      coding comes from the study of the detailed firing patterns of excitatory
      neurons. In the CA1 region of the rat hippocampus, pyramidal cells discharge
      selectively when the animal is in specific locations in its environment, and
      exhibit a precise relationship with the ongoing rhythmic activity of the network
      (phase precession). We demonstrate that during a spatial exploratory behavior on
      a linear track, inhibitory interneurons also show spatial selectivity and phase
      precession dynamics. We found that the firing rate of interneurons is modulated
      reliably up and down around an ongoing baseline activity level for specific
      locations in the environment, producing robust place-specific increases or
      decreases in discharge. On some sections of the track, the range of theta phases
      shifts progressively to earlier parts of the theta cycle as the rat advances, so
      that a negative correlation between phase and position could be demonstrated.
      Unlike pyramidal cells, phase and rate were not strongly correlated. We discuss
      the influence of the intrinsic firing properties of interneurons on a model of
      phase precession, as well as the influence of the detailed shape of the
      inhibitory oscillation. These results indicate that spatial selectivity and phase
      precession in CA1 are not properties restricted to pyramidal cells. Rather, they
      may be a more general expression of a common interaction between the different
      inputs impinging on both excitatory and inhibitory cells in CA1 and the intrinsic
      characteristics of those cells. Furthermore, they suggest that the role of
      interneurons may extend beyond a global damping of the network by participating
      in a finely-tuned local processing with the pyramidal cells.

PMID- 17183532
TI  - Expression of embryonic tau protein isoforms persist during adult neurogenesis in
      the hippocampus.
AB  - Tau is a microtubule-associated protein with a developmentally regulated
      expression of multiple isoforms. The neonatal isoform is devoid of two amino
      terminal inserts and contains only three instead of four microtubule-binding
      repeats (0N/3R-tau). We investigated the temporal expression pattern of 0N-tau
      and 3R-tau in the rat hippocampus. After the decline of 0N- and 3R-tau
      immunoreactivity during the postnatal development both isoforms remain highly
      expressed in a few cells residing beneath the granule cell layer. Coexpression of
      the polysialylated neuronal cell adhesion molecule, doublecortin, and
      incorporated bromodeoxyuridine showed that these cells are proliferating
      progenitor cells. In contrast mature granule cells express the adult tau protein
      isoform containing one aminoterminal insert domain (1N-tau). Therefore a shift in
      tau isoform expression takes place during adult neurogenesis, which might be
      related to migration, differentiation, and integration in the granule cell layer.
      A model for studying shifts in tau isoform expression in a defined subset of
      neurons might help to understand the etiology of tauopathies, when isoform
      composition is crucial for neurodegeneration, as in Pick's disease or FTDP-17.

PMID- 17183533
TI  - 1-Cyclohepta-2,4,6-trienyl-selanes--a 77Se NMR study: indirect nuclear 77Se--13C
      spin-spin coupling constants and application of density functional theory (DFT)
      calculations.
AB  - 1-Cyclohepta-2,4,6-trienyl-selanes Se(C(7)H(7))(2) (2c), R--Se--C(7)H(7) with R =
      Bu, (t)Bu, Ph, 4-F--C(6)H(4) (12a,b,c,d) were prepared by the reaction of the
      corresponding silanes, Si(SeMe(3))(2) and R--Se--SiMe(3), respectively, with
      tropylium bromide C(7)H(7)Br. In spite of the low stability of the selanes even
      in dilute solutions and at low temperature, they could be characterised by their
      (1)H, (13)C and (77)Se NMR parameters. Coupling constants (1)J((77)Se,(13)C) were
      measured and calculated by DFT methods at the B3LYP/6-311+G(d,p) level of theory.
      The comparison of experimental and calculated coupling constants
      (1)J((77)Se,(13)C) included numerous selenium carbon compounds with largely
      different Se--C bonds, revealing a satisfactory agreement. Both the spin-dipole
      (SD) and the paramagnetic spin-orbital (PSO) terms contributed significantly to
      the spin-spin coupling interaction, in addition to the Fermi contact (FC) term.

PMID- 17183534
TI  - Phylogenetic preservation of alpha3 Na+,K+-ATPase distribution in vertebrate
      peripheral nervous systems.
AB  - The alpha(3) isoform of Na(+),K(+)-ATPase is uniquely expressed in afferent and
      efferent neurons innervating muscle spindles in the peripheral nervous system
      (PNS) of adult rats, but the distribution pattern of this isoform in other
      species has not been investigated. We compared expression of alpha(3) Na(+),K(+)
      ATPase in lumbar dorsal root ganglia (DRG), spinal roots, and skeletal muscle
      samples of amphibian (frog), reptilian (turtle), avian (pigeon and chicken), and
      mammalian (mouse and human) species. In all species studied, the alpha(3)
      Na(+),K(+)-ATPase isoform was nonuniformly expressed in peripheral ganglia and
      nerves. In spinal ganglia, only 5-20% of neurons expressed this isoform, and, in
      avian and mammalian species, these alpha(3) Na(+),K(+)-ATPase-expressing neurons
      belonged to a subpopulation of large DRG neurons. In ventral root fibers of
      pigeons, mice, and humans, the alpha(3) Na(+),K(+)-ATPase was abundantly
      expressed predominantly in small myelinated axons. In skeletal muscle samples
      from turtles, pigeons, mice, and humans, alpha(3) Na(+),K(+)-ATPase was detected
      in intramuscular myelinated axons and in profiles of nerve terminals associated
      with the equatorial and polar regions of muscle spindle intrafusal fibers. These
      results show that the expression profiles for alpha(3) Na(+),K(+)-ATPase in the
      peripheral nervous system of a wide variety of vertebrate species are similar to
      the profile of rats and suggest that stretch receptor-associated expression of
      alpha(3) Na(+),K(+)-ATPase is preserved through vertebrate evolution.

PMID- 17183535
TI  - Distribution of RET immunoreactivity in the rodent spinal cord and changes after
      nerve injury.
AB  - RET (for "rearranged during transfection") is a transmembrane tyrosine kinase
      signaling receptor for members of the glial cell line-derived neurotrophic factor
      (GDNF) family of ligands. We used RET immunohistochemistry (IHC), double-labeling
      immunofluorescence (IF), and in situ hybridization (ISH) in adult naive and nerve
      injured rats to study the distribution of RET in the spinal cord. In the dorsal
      horn, strong RET-immunoreactive (-ir) fibers were abundant in lamina II-inner
      (II(i)), although this labeling was preferentially observed after an antigen
      unmasking procedure. After dorsal rhizotomy, RET-ir fibers in lamina II(i)
      completely disappeared from the dorsal horn, indicating that they were all
      primary afferents. After peripheral axotomy, RET-ir in primary afferents
      decreased in lamina II(i) and appeared to increase slightly in laminae III and
      IV. RET-ir was also observed in neurons and dendrites throughout the dorsal horn.
      Some RET-ir neurons in lamina I had the morphological appearance of nociceptive
      projection neurons, which was confirmed by the finding that 53% of RET-ir neurons
      in lamina I colocalized with neurokinin-1. GDNF-ir terminals were in close
      proximity to RET-ir neurons in the superficial dorsal horn. In the ventral horn,
      RET-ir was strongly expressed by motoneurons, with the strongest staining in
      small, presumably gamma-motoneurons. Increased RET expression following
      peripheral axotomy was most pronounced in alpha-motoneurons. The expression and
      regulation pattern of RET in the spinal cord are in line with its involvement in
      regenerative processes following nerve injury. The presence of RET in dorsal horn
      neurons, including nociceptive projection neurons, suggests that RET also has a
      role in signal transduction at the spinal level. This role may include mediating
      the effects of GDNF released from nociceptive afferent fibers.

PMID- 17183536
TI  - Heterogeneity of horizontal cells in the chicken retina.
AB  - Despite numerous reports that different markers are expressed by horizontal cells
      in the avian retina, it remains unknown whether different types of horizontal
      cells can be defined by differences in their immunocytochemical profiles. The
      purpose of this study was to rectify this deficiency. We identified horizontal
      cells by indirect immunofluorescence with antibodies to calretinin, trkA, GABA,
      Prox1, AP2alpha, Pax6, islet1, and Lim1 + 2. We found two major groups of
      horizontal cells, those that express trkA and those that express calretinin. The
      trkA-immunoreactive (-IR) horizontal cells had small, round somata and robust,
      bulbous dendritic endings, whereas calretinin-IR horizontal cells had large,
      polygonal cell bodies and fine, diffuse dendritic endings, both contacting the
      calbindin-IR pedicles of double cones. Weak gamma-aminobutyric acid (GABA)
      immunoreactivity was observed only in a few of the trkA-IR horizontal cells,
      whereas the overlap of calretinin and GABA immunoreactivities was 100%. The
      majority of trkA-IR horizontal cells expressed islet1, and the majority of
      calretinin-IR horizontal cells expressed Lim1 + 2, AP2alpha, and Pax6. Islet1
      immunoreactivity was observed in a small fraction of calretinin-IR/non-trkA-IR
      cells. In agreement with previous reports, we detected Prox1 immunoreactivity in
      all types of horizontal cells. These immunolabeling profiles suggest that there
      are four immunochemically distinct subtypes of horizontal cells in the postnatal
      chick retina, which may match the four types that have been observed in Golgi
      impregnated pigeon and turtle retinas.

PMID- 17183538
TI  - Functional and anatomical connection between the paraventricular nucleus of the
      thalamus and dopamine fibers of the nucleus accumbens.
AB  - The shell of the nucleus accumbens (NacSh) receives a dense innervation from
      dopamine (DA) neurons in the ventral tegmental area (VTA) and from glutamate
      neurons in the paraventricular nucleus of the thalamus (PVT). The present study
      examined in urethane-anesthetized rats the effects of electrical stimulation of
      the PVT on DA levels in the NacSh as measured with amperometry and
      chronoamperometry. Stimulation of the PVT (40 Hz, 1.0 ms, 400 microA, 5 seconds)
      resulted in a brief increase in electrochemical currents detected in the NacSh.
      Inhibition of DA neurons in the VTA using lidocaine (4%, 500 nL) or intravenous
      apomorphine (0.15 mg/kg) decreased the resting voltammetric signal but had no
      effect on PVT-evoked responses. Blocking of ionotropic glutamate receptors in the
      NacSh with local administration of kynurenic acid attenuated the PVT-evoked
      responses. Anterograde tracing with biotinylated dextran amine demonstrated that
      PVT targets regions of very dense tyrosine hydroxylase fiber staining in the
      NacSh. Consistent with the projection pattern of the PVT to the NacSh,
      stimulation of the PVT evoked the largest oxidation current changes in the NacSh,
      whereas small or no changes were elicited in other areas of the striatum. This
      study suggests that glutamate release from PVT terminals can act on ionotropic
      glutamate receptors in the NacSh to induce DA efflux. Modulation of DA levels in
      the NacSh by the PVT may be linked to arousal-induced increases in DA tone and
      could be involved in the facilitation of specific behavioral patterns associated
      with arousal or stressful situations.

PMID- 17183539
TI  - Compensatory and transneuronal plasticity after early collicular ablation.
AB  - Plasticity within the visual system was assessed in the quokka wallaby following
      unilateral superior collicular (SC) ablation at postnatal days (P) 8-10, prior to
      the arrival of retinal ganglion cell (RGC) axons. At maturity (P100), projections
      were traced from the eye opposite the ablation, and total RGC numbers were
      estimated for both eyes. Ablations were partial (28-89% of SC remaining) or
      complete (0-5% of SC remaining). Projections to the visual centers showed
      significant bilateral (P < 0.05) increases in absolute volume. Minor anomalous
      projections also formed within the deep, surviving non-retino-recipient layers of
      the ablated SC and via a small bundle of RGC axons recrossing the midline to
      innervate discrete patches in the SC contralateral to the lesion. Total absolute
      volume of projections did not differ between partial and complete ablations;
      moreover, values did not differ from normal (P > 0.05). Compared with normal,
      total RGC numbers were significantly (P < 0.05) reduced in the eye opposite the
      ablation but increased (P < 0.05) in the other eye. Consequently, the sum of the
      two RGC populations did not differ from normal (P > 0.05). As in rodents, the
      visual system in quokka compensates following injury by maintaining a set volume
      of arborization but does so by forming only minor anomalous projections.
      Furthermore, increased RGC numbers in the eye ipsilateral to the lesion indicate
      that compensation occurs transneuronally, thus maintaining total numbers of
      projecting neurons. The implication is that the visual system acts in concert
      following unilateral injury to maintain set values for RGC terminal arbors as
      well as their cell bodies.

PMID- 17183537
TI  - Collateralization of the tectonigral projection with other major output pathways
      of superior colliculus in the rat.
AB  - Dopaminergic (DA) neurons exhibit a short-latency, phasic response to unexpected,
      biologically salient stimuli. The superior colliculus (SC) is also sensitive to
      such stimuli and sends a projection directly to DA-containing regions of the
      ventral midbrain. Recent evidence suggests that the SC is a critical relay for
      transmitting short-latency visual information to DA neurons. An important
      question is whether the ventral midbrain is an exclusive target of tectonigral
      neurons, or whether the tectonigral projection is a collateral branch of other
      tectofugal pathways. Double-label retrograde anatomical tracing techniques were
      used to address this issue. Injections of either Diamidino Yellow or Fluorogold
      into substantia nigra pars compacta (SNc) were combined with larger injections of
      True Blue into one of the following efferent projections of the SC: 1) target
      regions of the ipsilateral ascending projection to the thalamus; 2) the crossed
      descending tecto-reticulo-spinal pathway; 3) target structures of the ipsilateral
      descending projection; and 4) the contralateral superior colliculus. Moderate
      numbers of double-labeled neurons were observed following combined injections
      into substantia nigra and individual nuclei in the thalamus (ventromedial
      nucleus, 21.3%; central lateral, 18.4%; parafasicular nucleus 6.0%). Much less
      double-labeling was associated with injections into either of the descending
      projections (crossed, 1.0-3.2%; uncrossed, 0.2-2.7%) or the contralateral SC (0.7
      1.9%). These results suggest: i) the SC may provide a coordinated input
      concerning the occurrence of unpredicted sensory events to both the substantia
      nigra and striatum (via the thalamus); and ii) few gaze-related motor signals are
      simultaneously relayed to DA-containing regions of the ventral midbrain.

PMID- 17183540
TI  - Cytoarchitectonic and chemoarchitectonic subdivisions of the perirhinal and
      parahippocampal cortices in macaque monkeys.
AB  - Although the perirhinal and parahippocampal cortices have been shown to be
      critically involved in memory processing, the boundaries and extent of these
      areas have been controversial. To produce a more objective and reproducible
      description, the architectonic boundaries and structure of the perirhinal (areas
      35 and 36) and parahippocampal (areas TF and TH) cortices were analyzed in three
      macaque species, with four different staining methods [Nissl and
      immunohistochemistry for parvalbumin, nonphosphorylated neurofilaments (with SMI
      32), and the m2 muscarinic acetylcholine receptor]. We further correlated the
      architectonic boundary of the parahippocampal cortex with connections to and from
      different subregions of anterior area TE and with previously published
      connections with the prefrontal cortex and temporal pole (Kondo et al. [2005] J.
      Comp. Neurol. 493:479-509). Together, these data provided a clear delineation of
      the perirhinal and parahippocampal areas, although it differs from previous
      descriptions. In particular, we did not extend the perirhinal cortex into the
      temporal pole, and the lateral boundaries of areas 36 and TF with area TE were
      placed more medially than in other studies. The lateral boundary of area TF in
      Macaca fuscata was located more laterally than in Macaca fascicularis or Macaca
      mulatta, although there was no difference in architectonic structure. We
      recognized a caudal, granular part of the parahippocampal cortex that we termed
      "area TFO." This area closely resembles the laterally adjacent area TE and the
      caudally adjacent area V4 but is clearly different from the more rostral area TF.
      These areas are likely to have distinct functions.

PMID- 17183541
TI  - Distribution of vasopressin in the brain of the eusocial naked mole-rat.
AB  - Naked mole-rats are eusocial rodents that live in large subterranean colonies in
      which one queen breeds with one to three males. All other animals are nonbreeding
      subordinates. The external features of male and female subordinates, including
      their genitalia, are remarkably monomorphic, as is their behavior. Because
      vasopressin (VP) is associated with social behaviors and sex differences in other
      species, its distribution in naked mole-rats was of interest. We used
      immunohistochemistry to examine VP in the brains of subordinate and breeding
      naked mole-rats of both sexes. As in other mammals, VP-immunoreactive (-ir)
      somata were found in the paraventricular (PVN) and supraoptic nuclei (SON) and VP
      ir projections from these nuclei ran through the internal and external zone of
      the median eminence. However, naked mole-rats had very few VP-ir cells in the bed
      nucleus of the stria terminalis (BST) and none in the suprachiasmatic nucleus
      (SCN); the extensive network of fine-caliber VP-ir fibers usually seen in
      projection sites of the BST and SCN were also absent. Equally unexpected was the
      abundance of large-caliber VP-ir fibers in the dorsomedial septum. VP
      immunoreactivity was generally similar in all groups, with the exception of VP-ir
      cell number in the dorsomedial hypothalamus (DMH). Breeders had a population of
      labeled cells in the DMH that was absent, or nearly absent, in subordinates.
      Future studies on the function of VP in these areas are needed to determine how
      the atypical distribution of VP immunoreactivity relates to eusociality and the
      unusual physiology of naked mole-rats.

PMID- 17183543
TI  - Alpha-smooth muscle actin expression enhances cell traction force.
AB  - Using an established corneal stromal cell differentiation model, we manipulated
      alpha-smooth muscle actin (alpha-SMA) protein expression levels in fibroblasts by
      treating them with TGF-beta1, bFGF, TGF-beta type I receptor inhibitor (SB
      431542), and siRNA against alpha-SMA. The corresponding cell traction forces
      (CTFs) were determined by cell traction force microscopy. With all these
      treatments, we found that alpha-SMA is not required for CTF induction, but its
      expression upregulates CTF. This upregulation involves the modification of stress
      fibers but does not appear to relate to non-muscle myosin II expression or beta
      actin expression. Moreover, there exists a linear relationship between alpha-SMA
      protein expression level and CTF magnitude. Finally, CTFs were found to vary
      among a population of myofibroblasts, suggesting that alpha-SMA protein
      expression levels of individual cells also vary.

PMID- 17183542
TI  - Estradiol enhances neurogenesis following ischemic stroke through estrogen
      receptors alpha and beta.
AB  - Neurogenesis persists throughout life under normal and degenerative conditions.
      The adult subventricular zone (SVZ) generates neural stem cells capable of
      differentiating to neuroblasts and migrating to the site of injury in response to
      brain insults. In the present study, we investigated whether estradiol increases
      neurogenesis in the SVZ in an animal model of stroke to potentially promote the
      ability of the brain to undergo repair. Ovariectomized C57BL/6J mice were
      implanted with capsules containing either vehicle or 17beta-estradiol, and 1 week
      later they underwent experimental ischemia. We utilized double-label
      immunocytochemistry to identify the phenotype of newborn cells (5-bromo-2'
      deoxyuridine-labeled) with various cellular markers; doublecortin and PSA-NCAM as
      the early neuronal marker, NeuN to identify mature neurons, and glial fibrillary
      acidic protein to identify astrocytes. We report that low physiological levels of
      estradiol treatment, which exert no effect in the uninjured state, significantly
      increase the number of newborn neurons in the SVZ following stroke injury. This
      effect of estradiol is limited to the dorsal region of the SVZ and is absent from
      the ventral SVZ. The proliferative actions of estradiol are confined to neuronal
      precursors and do not influence gliosis. Furthermore, we show that both estrogen
      receptors alpha and beta play pivotal functional roles, insofar as knocking out
      either of these receptors blocks the ability of estradiol to increase
      neurogenesis. These findings clearly demonstrate that estradiol stimulates
      neurogenesis in the adult SVZ, thus potentially facilitating the brain to remodel
      and repair after injury.

PMID- 17183544
TI  - Tumor-derived factors impaired motility and immune functions of dendritic cells
      through derangement of biophysical characteristics and reorganization of
      cytoskeleton.
AB  - The generation and progress of tumors are accompanied with a marked suppression
      of human immune system. To explore the mechanisms by which tumors escape from
      immune recognition, we studied the influences of tumor microenvironment on
      differentiation of dendritic cells (DCs), which play an important role in tumor
      immunology, by biophysical and immunological methods. It was found that the
      cytokines derived from tumors caused an increase in osmotic fragility and a
      decrease in membrane fluidity of DCs, disordering and elevated expression levels
      of cytoskeleton, and changes of the gene transcriptional levels and energy status
      of the cells. Moreover, IL-12 production and the expression levels of some
      surface-marker molecules were also suppressed. These changes led to impaired
      capabilities of antigen uptake, cell motility and naive T cell activation; the
      abnormal biophysical characteristics of DCs may be one aspect of the immune
      escape mechanism of tumor. These results provide insights into the importance of
      the reconstruction of tumor microenvironment for immunotherapy based on the anti
      cancer activities of DCs.

PMID- 17183545
TI  - Talin2 is induced during striated muscle differentiation and is targeted to
      stable adhesion complexes in mature muscle.
AB  - The cytoskeletal protein talin serves as an essential link between integrins and
      the actin cytoskeleton in several similar, but functionally distinct, adhesion
      complexes, including focal adhesions, costameres, and intercalated disks.
      Vertebrates contain two talin genes, TLN1 and TLN2, but the different roles of
      Talin1 and Talin2 in cell adhesion are unclear. In this report we have analyzed
      Talin1 and Talin2 in striated muscle. Using isoform-specific antibodies, we found
      that Talin2 is highly expressed in mature striated muscle. Using mouse C2C12
      cells and primary human skeletal muscle myoblasts as models of muscle
      differentiation, we show that Talin1 is expressed in undifferentiated myoblasts
      and that Talin2 expression is upregulated during muscle differentiation at both
      the mRNA and protein levels. We have also identified regulatory sequences that
      may be responsible for the differential expression of Talin1 and Talin2. Using
      GFP-tagged Talin1 and Talin2 constructs, we found that GFP-Talin1 targets to
      focal adhesions while GFP-Talin2 targets to abnormally large adhesions in
      myoblasts. We also found that ectopic expression of Talin2 in myoblasts, which do
      not contain appreciable levels of Talin2, dysregulates the actin cytoskeleton.
      Finally we demonstrate that Talin2, but not Talin1, localizes to costameres and
      intercalated disks, which are stable adhesions required for the assembly of
      mature striated muscle. Our results suggest that Talin1 is the primary link
      between integrins and actin in dynamic focal adhesions in undifferentiated,
      motile cells, but that Talin2 may serve as the link between integrins and the
      sarcomeric cytoskeletonin stable adhesion complexes in mature striated muscle.

PMID- 17183547
TI  - Insight into the mechanism of fast movement of myosin from Chara corallina.
AB  - Chara myosin, two-headed plant myosin belonging to class XI, slides F-actin at
      maximally 60 microm s(-1). To elucidate the mechanism of this fast sliding, we
      extensively investigated its mechanochemical properties. The maximum actin
      activated ATPase activity, Vmax, was 21.3 s(-1) head(-1) in a solution, but when
      myosin was immobilized on the surface, its activity was 57.6 s(-1) head(-1) at 2
      mg ml(-1) of F-actin. The sliding velocity and the actin activated ATPase
      activity were greatly inhibited by ADP, suggesting that ADP dissociation was the
      rate limiting step. With the extensive assay of motility by varying the surface
      density, the duty ratio of Chara myosin was found to be 0.49-0.44 from velocity
      measurements and 0.34 from the landing rate analysis. At the surface density of
      10 molecules microm(-2), Chara myosin exhibited pivot movement under
      physiological conditions. Based on the results obtained, we will discuss the
      sliding mechanism of Chara myosin according to the working stroke model in terms
      of its physiological aspects. aspects.

PMID- 17183546
TI  - MEK/ERK regulates adherens junctions and migration through Rac1.
AB  - Polyamine depletion with the ornithine decarboxylase inhibitor alpha
      difluoromethyl ornithine (DFMO), prevents Rac1 activation causing the formation
      of a thick actin cortex at the cell periphery and inhibits migration of
      intestinal epithelial cells. In the present study, we demonstrate that MEK
      activation by EGF increased Rac1 activation, dissociation of intercellular
      contacts, and migration in both control and polyamine-depleted cells, while
      U0126, a specific inhibitor of MEK1, prevented disruption of junctions as well as
      EGF-induced Rac1 activation. Constitutively active MEK1 (CA-MEK) expression
      altered cell-cell contacts in control and polyamine depleted cells. The
      expression of constitutively active Rac1 (CA-Rac1) restored beta-catenin to the
      cell periphery and prevented the formation of actin cortex and caused the
      appearance of F-actin stress fibers in polyamine-depleted cells. Inhibition of
      Rac activation by NSC23766, a specific inhibitor of Tiam1, an upstream guanidine
      nucleotide exchange factor for Rac1, reproduced the beta-catenin localization and
      actin structure of polyamine-depleted cells. Tiam1 localized more extensively
      with beta-catenin at the cell periphery in CA-Rac1 cells compared to vector
      cells. Polyamine depletion decreased the expression of E-cadherin to a greater
      extent compared to beta-catenin. Subcellular fractionation further confirmed our
      immuno-localization and western blotting observations. These data suggest that
      EGF acting through MEK1/ERK to activate Rac1 regulates cell-cell contacts. Thus,
      decreased migration in polyamine depleted cells may be due to the inhibition of
      Tiam1 activation of Rac1 and the subsequent decreased expression of beta-catenin
      and E-cadherin leading to reduced cell-cell contacts.

PMID- 17183548
TI  - Reconstitution in vitro of MSP-based filopodium extension in nematode sperm.
AB  - The major sperm protein (MSP) motility system in nematode sperm is best known for
      propelling the movement of mature sperm, where it has taken over the role usually
      played by actin in amoeboid cell motility. However, MSP filaments also drive the
      extension of filopodia, transient organelles composed of a core bundle of MSP
      filaments, that form in the late in sperm development but are not found on
      crawling cells. We have reconstituted filopodial extension in vitro whereby thin
      bundles of MSP filaments, each enveloped by a membrane sheath at their growing
      end, elongated at rates up to 17 microm/min. These bundles often exceeded 500
      microm in length but were comprised of filaments only 1 microm long. The
      reconstituted filopodia assembled in the same cell-free sperm extracts that
      produced MSP fibers, robust meshworks of filaments that exhibit the same
      organization and dynamics as the lamellipodial filament system that propels sperm
      movement. The filopodia and fibers that assembled in vitro both had a membranous
      structure at their growing end, shared four MSP accessory proteins, and responded
      identically to agents that alter MSP-based motility by modulating protein
      phosphorylation. However, filopodia grew three- to four-fold faster than fibers.
      The reconstitution of filopodial extension shows that, like the actin
      cytoskeleton, MSP filaments can adopt two architectures, bundles and meshworks,
      each capable of pushing against membranes to generate protrusion. The
      reconstitution of both forms of motility in the same in vitro system provides a
      promising avenue for understanding how the forces for membrane protrusion are
      produced.

PMID- 17183549
TI  - Parkinson's disease and working capacity.
AB  - The purpose of the present study was to establish how Parkinson's disease (PD)
      affects working capacity. Altogether, 937 (70%) of 1,343 working-aged members of
      the Finnish Parkinson Association participated in a questionnaire study. The ages
      of the subjects were between 29 and 65 years, median 59.0 years; 508 (54%) were
      men. The median (quartile range) duration of PD symptoms was 7.3 (4.3-11.3)
      years, and the median self-estimated severity of the disease on the Hoehn & Yahr
      scale was 2. Only 150 of 937 subjects (16%) were still working: 112 (12%) full
      time and 38 (4%) part-time. Among those 343 (37%) who had retired purely because
      of PD at a median age of 53.4 years, the median working time was 1.7 years after
      established diagnosis. In part-time work, PD patients had been able to continue
      for a median of 4.3 years. PD often leads to early retirement; compared with the
      general Finnish population of similar age, PD patients had retired on the average
      6 years earlier. Young age, mild symptoms, and short duration of the disease as
      well as adjustments enabling easier employment were associated with the
      possibility to continue longer in the work force.

PMID- 17183550
TI  - Connexin 43 is localized with actin in tenocytes.
AB  - Varieties of cell-matrix or cell-cell adhesions are associated with the actin
      cytoskeleton. However, for gap junctions, which are both channels and adhesions,
      there has been little evidence for such an association. The purpose of this study
      was to determine if connexin 43 (Cx43) associates with actin and to determine if
      this association is altered under mechanical load in tenocytes, a mechanically
      sensitive cell. Avian tenocytes were subjected to multiple cyclic strain regimens
      and then fixed and examined immunohistochemically at various times poststrain to
      determine where Cx43 protein was localized within the cells in relation to actin
      filaments. Four percent of tenocytes had colocalization of actin filaments and
      Cx43, which was significantly increased with 5% cyclic strain. To confirm this
      phenomenon, human tenocytes and COS-7 cells were also subjected to cyclic strain
      and then fixed at the same times after strain. As with avian tenocytes, Cx43 was
      colocalized with actin in human tenocytes and COS-7 cells. The colocalization
      increased significantly after cyclic strain in human tenocytes but not in COS-7
      cells. The lack of detectable changes in COS-7 cells may indicate that they are
      less mechanosensitive than tenocytes perhaps due to the less robust actin
      cytoskeleton seen in the COS-7 cells when compared to the tenocytes. Furthermore,
      inhibiting myosin II activity greatly reduced the immunohistochemically
      detectable Cx43 on actin filaments. Connexins may associate with actin to
      stabilize gap junctions at the plasma membrane, ensuring that tenocytes remain
      coupled during periods of prolonged or intense mechanical loading.

PMID- 17183552
TI  - Identification of aldolase C compartments in the mouse cerebellar cortex by
      olivocerebellar labeling.
AB  - Aldolase C (zebrin II) is expressed in Purkinje cells aligned in complicated
      longitudinal stripe-shaped compartments. The tight link between these aldolase C
      compartments and the topographic olivocerebellar projection to them has made it
      possible to identify each compartment as a target of a specific subarea of the
      inferior olive and thus as a functionally distinct entity in the rat. However, it
      is unknown whether the overall organization of aldolase C compartments is
      preserved in other mammals. In this study, we tried to clarify this organization
      in the mouse, which is more useful in genetic studies than the rat, by
      identifying each aldolase C compartment in terms of the olivocerebellar
      projection pattern. First, aldolase C compartments were reconstructed from serial
      sections throughout the cerebellar cortex. Aldolase C and olivocerebellar
      climbing fibers were then doubly labeled by small injections of biotinylated
      dextran amine into various areas of the inferior olive. Climbing fibers were
      topographically distributed on a specific linked pair of aldolase C compartments
      in the rostral and caudal cerebellum. The overall relationship between aldolase C
      compartments and the topographic olivocerebellar projection to them in the mouse
      was similar to that in the rat, except for some minor differences, suggesting
      that the aldolase C compartments and olivocerebellar projection are organized
      according to a common fundamental organization in the mouse and rat. This allowed
      the unequivocal identification of all aldolase C compartments in the mouse by
      referring to the definition and nomenclature in the rat.

PMID- 17183553
TI  - Perisynaptic organization of plasma membrane calcium pumps in cerebellar cortex.
AB  - Calcium, a ubiquitous intracellular messenger, regulates numerous intracellular
      signaling pathways. To permit specificity of signal transduction and prevent
      unwanted cross-talk between pathways, sites of calcium entry in neurons are
      localized to specific membrane domains. To test whether Ca(2+) extrusion pumps
      might exhibit analogous compartmentalization, we used immunohistochemistry to
      determine the subcellular localization of the two main plasma membrane Ca(2+)
      ATPase (PMCA) isoforms in the cortex of the rat cerebellum. We find that both
      PMCA2 and PMCA3 are targeted to distinct compartments within the plasma membrane.
      In the molecular layer, both isoforms were at highest levels within synaptic
      profiles, but PMCA2 was postsynaptic and PMCA3 was presynaptic. Moreover, inside
      these compartments, both pumps exhibited nonuniform distributions. These data
      imply that cerebellar neurons possess remarkably effective mechanisms to target
      and restrict PMCA2 and -3 to specific membrane domains, raising the possibility
      that calcium pumps contribute to local Ca(2+) signaling.

PMID- 17183555
TI  - Adrenalectomy-induced granule cell degeneration in the hippocampus causes spatial
      memory deficits that are not reversed by chronic treatment with corticosterone or
      fluoxetine.
AB  - Long-term adrenalectomy (ADX) causes a nearly complete and selective loss of
      granule cells in the dentate gyrus (DG) of the hippocampus. Previously, learning
      and memory deficits have been observed following ADX-induced granule cell
      degeneration for tasks that require the hippocampus. Our objective here was to
      determine whether corticosterone (CORT) replacement and treatment with the
      neurogenic compound fluoxetine could reverse behavioral deficits after ADX. We
      trained ADX and control rats in a moving, hidden platform version of the Morris
      water task before chronic administration (6 weeks) of CORT and either fluoxetine
      or vehicle. After treatment, all rats were retested in the Morris water task.
      Brains were labeled for the endogenous neurogenic markers Ki67 and doublecortin.
      Here we provide evidence that neurogenesis persists at a normal rate in the
      hippocampus after long-term ADX. After 8 weeks of CORT and fluoxetine
      administration, ADX-fluoxetine rats did not differ significantly compared to ADX
      vehicle rats receiving CORT or compared to control rats in the number of Ki67 or
      doublecortin labeled cells. ADX-fluoxetine rats also did not significantly differ
      from ADX-vehicle rats in regards to granule cell layer thickness. Our results
      indicate that long-term ADX is associated with impaired spatial ability in the
      Morris water task and that neither chronic treatment with CORT, nor with CORT and
      fluoxetine are capable of altering the Morris water task deficit.

PMID- 17183557
TI  - Testosterone replacement for hypogonadism after treatment of early prostate
      cancer with brachytherapy.
AB  - BACKGROUND: Controversy and a notable paucity of published clinical data best
      characterize the current knowledge of testosterone-replacement therapy (TRT) for
      hypogonadism after treatment for early, localized prostate cancer. The objective
      of this study was to assess the risk of biochemical failure with TRT after
      treatment of early prostate cancer with permanent transperineal brachytherapy
      with or without external beam therapy in patients with low serum levels of
      testosterone and clinical symptoms of hypogonadism. METHODS: Patients who
      underwent prostate brachytherapy from 1996 to 2004 and received subsequent TRT
      for symptomatic hypogonadism were reviewed to detail cancer characteristics and
      treatment as well as pre- and post-TRT serum testosterone and prostate-specific
      antigen (PSA) values. RESULTS: Thirty-one men received TRT after prostate
      brachytherapy for 0.5 to 8.5 years (median, 4.5 years), with a follow-up that
      ranged from 1.5 years to 9.0 years (median, 5.0 years) postbrachytherapy. TRT was
      started from 0.5 years to 4.5 years (median, 2.0 years) after brachytherapy.
      Serum total testosterone levels ranged from 30 ng/dL to 255 ng/dL (median, 188
      ng/dL) before TRT and rose to 365 ng/dL to 1373 ng/dL (median, 498 ng/dL) on TRT.
      Transient rises in PSA were observed in 1 patient. The most recent PSA level was
      <0.1 ng/mL in 23 patients (74.2%), <0.5 ng/mL in 30 patients (96.7%), and <1
      ng/mL in 31 patients (100%). No patients stopped TRT because of cancer recurrence
      or documented cancer progression. CONCLUSIONS: For patients with low serum
      testosterone levels and symptoms of hypogonadism, TRT may be used with caution
      and close follow-up after prostate brachytherapy.

PMID- 17183556
TI  - Periosteal margin in soft-tissue sarcoma.
AB  - BACKGROUND: Soft-tissue sarcomas frequently rest in contact with bone. The
      purpose of the study was to evaluate the risk of local recurrence for sarcomas
      adjacent to bone and to determine whether the periosteum provides an adequate
      margin of resection. METHODS: Fifty patients with soft-tissue sarcomas abutting
      bone were treated at a single institution between 1990 and 2004. All patients had
      high-grade, T2 (>5 cm), nonmetastatic disease in the lower extremity. Bone
      contact was verified by preoperative magnetic resonance imaging (MRI) and/or
      computed tomography (CT) scans. Forty-three of 50 patients received preoperative
      radiation with a mean dose of 50 Gy. In 11 cases a composite resection of bone
      and soft tissue was performed. In 39 cases the excision involved only soft
      tissue. RESULTS: True bone invasion was verified by histopathologic examination
      in 3 of 50 cases (6%). Local recurrence in the soft tissues developed in 8 of 50
      (16%) patients. In no case did the recurrence involve destruction of cortical
      bone or erosion into bone. The recurrent tumor resided against the region of
      previous bone contact in 1 of 8 cases. There was no statistically significant
      difference in local recurrence between patients who had composite bone resection
      and patients who had soft-tissue resection only (P = .87). CONCLUSIONS:
      Relatively few sarcomas are able to penetrate cortical bone. Composite bone and
      soft-tissue resections are indicated primarily for frank bone invasion. In the
      absence of this, the periosteum is an adequate surgical margin for sarcomas
      treated with wide excision and radiation.

PMID- 17183558
TI  - Prognostic significance of vascular endothelial growth factor protein levels in
      T1-2 N0 laryngeal cancer treated with primary radiation therapy.
AB  - BACKGROUND: The purpose of this study was to assess the prognostic value of
      vascular endothelial growth factor protein levels in a large cohort of patients
      with T1-T2 N0 laryngeal cancer treated with primary radiation therapy (XRT).
      METHODS: Primary tumor specimens from a cohort of 123 patients with T1-T2 N0
      laryngeal cancer treated with XRT between 1975 and 2000 were constructed into a
      tissue microarray. Clinical prognostic factors included age, sex, T
      classification, and tumor subsite. Molecular prognostic factors included vascular
      endothelial growth factor, epidermal growth factor receptor, and p53 expression,
      determined by using immunohistochemistry on tissue microarrays. The association
      between vascular endothelial growth factor status, covariables, and outcome was
      assessed. RESULTS: With a median follow-up of 9.9 years, 32 (26%) were diagnosed
      with local relapse (5-year local relapse-free rate, 70.4%). T2 tumor stage
      (31.7%) was a significant predictor of local relapse (relative risk [RR], 1.71;
      95% confidence interval [CI], 1.21-2.43; P<.05). Positive expression of vascular
      endothelial growth factor, epidermal growth factor receptor, and p53 were: 8.5%,
      58.7%, and 36.4%, respectively. In univariate analysis, vascular endothelial
      growth factor positivity was a significant predictor of overall survival (RR =
      1.62; 95% CI, 0.99-2.42; P = .05). In multivariate analysis, positive vascular
      endothelial growth factor status maintained significant correlation with overall
      survival (RR, 2.79; 95% CI, 1.49-4.95; P = .002). CONCLUSIONS: Vascular
      endothelial growth factor positivity appeared to be a significant predictor of
      overall survival in a multivariate model. Further evaluation of vascular
      endothelial growth factor-positive laryngeal cancers treated with primary XRT is
      warranted.

PMID- 17183554
TI  - Chemokine receptor expression by neural progenitor cells in neurogenic regions of
      mouse brain.
AB  - We previously demonstrated that chemokine receptors are expressed by neural
      progenitors grown as cultured neurospheres. To examine the significance of these
      findings for neural progenitor function in vivo, we investigated whether
      chemokine receptors were expressed by cells having the characteristics of neural
      progenitors in neurogenic regions of the postnatal brain. Using in situ
      hybridization we demonstrated the expression of CCR1, CCR2, CCR5, CXCR3, and
      CXCR4 chemokine receptors by cells in the dentate gyrus (DG), subventricular zone
      of the lateral ventricle, and olfactory bulb. The pattern of expression for all
      of these receptors was similar, including regions where neural progenitors
      normally reside. In addition, we attempted to colocalize chemokine receptors with
      markers for neural progenitors. In order to do this we used nestin-EGFP and TLX
      LacZ transgenic mice, as well as labeling for Ki67, a marker for dividing cells.
      In all three areas of the brain we demonstrated colocalization of chemokine
      receptors with these three markers in populations of cells. Expression of
      chemokine receptors by neural progenitors was further confirmed using CXCR4-EGFP
      BAC transgenic mice. Expression of CXCR4 in the DG included cells that expressed
      nestin and GFAP as well as cells that appeared to be immature granule neurons
      expressing PSA-NCAM, calretinin, and Prox-1. CXCR4-expressing cells in the DG
      were found in close proximity to immature granule neurons that expressed the
      chemokine SDF-1/CXCL12. Cells expressing CXCR4 frequently coexpressed CCR2
      receptors. These data support the hypothesis that chemokine receptors are
      important in regulating the migration of progenitor cells in postnatal brain.

PMID- 17183559
TI  - Human hepatoblast phenotype maintained by hyaluronan hydrogels.
AB  - Human hepatoblasts and hepatic stem cells, pluripotent hepatic progenitors that
      give rise to hepatocytes and biliary cells, were isolated from fetal livers and
      found to express hyaluronan receptors (CD44) in both the freshly isolated cells
      and after culture. This implicates an in vivo connection to hyaluronan (HA), an
      embryonic matrix component, as a candidate 3-dimensional (3-D) scaffold for
      hepatic progenitor cell expansion and/or differentiation. To assess HAs as
      scaffolds, hepatoblasts and hepatic stem cells were seeded into HA hydrogels with
      a serum-free, hormonally defined medium tailored for expansion of hepatic
      progenitors. Cell aggregates formed within the HA hydrogels and remained viable,
      proliferative, and demonstrated a stable phenotype intermediate between that of
      hepatic stem cells and hepatoblasts throughout more than 4 weeks of culturing,
      with little evidence of lineage restriction towards either hepatocytic or biliary
      pathways. The phenotype consisted of stable co-expression of both hepatocytic and
      biliary markers such as biliary-specific cytokeratin, CK19, low levels of
      expression of albumin, and urea synthesis. HA hydrogels are ideal as 3-D
      scaffolds for pluripotent hepatic progenitors and should be useful for generating
      cells to be used in bioartificial livers or tissue engineered liver grafts.

PMID- 17183560
TI  - Effects of airborne-particle abrasion, sodium hydroxide anodization, and
      electrical discharge machining on porcelain adherence to cast commercially pure
      titanium.
AB  - The aim of this study was to determine the effect of airborne-particle abrasion
      (APA), sodium hydroxide anodization (SHA), and electrical discharge machining
      (EDM) on cast titanium surfaces and titanium-porcelain adhesion. Ninety titanium
      specimens were cast with pure titanium and the alpha-case layer was removed.
      Specimens were randomly divided into three groups. Ten specimens from each group
      were subjected to APA. SHA was applied to the second subgroups, and the remaining
      specimens were subjected to the EDM. For the control group, 10 specimens were
      cast using NiCr alloy and subjected to only APA. Surfaces were examined by using
      scanning electron microscope and a surface profilometer. Three titanium
      porcelains were fused on the titanium surfaces, whereas NiCr specimens were
      covered with conventional porcelain. Titanium-porcelain adhesion was
      characterized by a 3-point bending test. Statistical analysis showed that the
      porcelain-metal bond strength of the control group was higher than that of the
      titanium-porcelain system (p < 0.05). There were no significant differences
      between the bond strengths of titanium groups (p 0.05), except the bond strengths
      of Noritake Super Porcelain TI-22 groups on which APA and SHA were applied (p <
      0.05). SHA and EDM as surface treatment did not improve titanium-porcelain
      adhesion when compared to APA.

PMID- 17183561
TI  - Mechanical and biocompatible influences of chitosan fiber and gelatin on calcium
      phosphate cement.
AB  - Calcium phosphate cement (CPC) is a widely used bone substitute in the clinic;
      however, the low strength of CPC limits its utilization. In this study, we
      investigated mechanical influences of chitosan fiber combined with gelatin on
      CPC, and examined the biocompatibility of the new composite with rat bone marrow
      stromal cells. Compared to the fiber impregnated in phosphate buffered saline
      (80.5 MPa), our study showed that tensile strength of chitosan fiber increased
      106 and 114% with the impregnation of gelatin at the mass fraction 5 and 10%,
      although this increase was not statistically significant. It was demonstrated by
      Fourier transform infrared spectroscopy that the characteristic absorption bands
      of chitosan were changed with the addition of gelatin. The optimal flexural
      strength enhancement was obtained when CPC was reinforced with fiber at volume
      fraction of 30% and gelatin at mass fraction of 5% (maximum: 12.31 MPa). The
      fiber morphology was more compact when the chitosan fibers impregnated with
      gelatin at mass fraction of 5 or 10% than chitosan alone. The fracture analysis
      showed that the new CPC-chitosan fiber-gelatin composite presented many remnants
      of CPC adhered to fibers. Short minimum essential medium extract test showed no
      cell growth inhibition after the addition of the new composite. Rat bone marrow
      stromal cells retain the ability to spread and grow on the composite. Our studies
      demonstrated that the flexural strength is greatly increased by using CPC
      incorporated with proper ratio of CF and gelatin. More over, the new composite
      demonstrated biocompatibility in vitro.

PMID- 17183562
TI  - Mechanical properties and biological behavior of carbon nanotube/polycarbosilane
      composites for implant materials.
AB  - Multiwalled carbon nanotube/polycarbosilane (MWCNT/PCS) composites were
      fabricated by the spark plasma sintering (SPS) method. The MWCNT/PCS composites
      consisted of MWCNTs and nanosized SiC particles pyrolyzed from PCS and possessing
      good mechanical properties for bone tissue repair or dental implantation. The
      MWCNT/PCS composites were implanted in the subcutaneous tissue and femur of rats
      at 1 and 4 weeks after implantation. Histological investigations showed that
      there was little inflammatory response in the subcutaneous tissue, and newly
      formed bone tissue was observed in the femur. These results indicated that the
      MWCNT/PCS composite had little prophlogistic effect and good osteoconductivity.
      The study suggested the possibility that the MWCNT/PCS composite could be a
      candidate bone-substitute and dental-implant material in the future.

PMID- 17183563
TI  - BMP-7 loaded microspheres as a new delivery system for the cultivation of human
      chondrocytes in a collagen type-I gel.
AB  - In recent years, interest in chondrocyte cultures for transplantation has gained
      increasing attention. We investigated the use of PGLA microspheres as a new
      delivery system for BMP-7 and the effects on human chondrocytes cultivated in a
      3D collagen gel culture. In an in vitro study, human chondrocytes obtained from
      osteoarthritic knee joints were released, transferred into a collagen type-I gel,
      and cultivated up to 14 days. In the treatment group PGLA microspheres loaded
      with human recombinant BMP-7 protein were added to the matrix. After the
      cultivation period, histological and immunohistochemical investigations were
      performed. In addition, the aggrecan core protein and type-II collagen mRNA
      concentrations were measured by real-time PCR. Histological staining for
      proteoglycan and collagen type-II protein and quantification via digital image
      processing revealed a significantly higher content in the samples cultivated with
      BMP-7 loaded microspheres in comparison to the control samples. Moreover, the
      collagen gel scaffold was partially remodeled by the chondrocytes and replaced by
      newly synthesized extracellular matrix. Cellular proliferation as well as
      apoptosis were low. In conclusion, we consider the PGLA microsphere system to be
      a functional device for the delivery of growth factors during the cultivation of
      articular chondrocytes leading to an increased content of type-II collagen and
      proteoglycan in the extracellular matrix.

PMID- 17183564
TI  - Comparison of drying methods in the fabrication of collagen scaffold via indirect
      rapid prototyping.
AB  - Porous collagen scaffolds with predefined 3-dimesional (3-D) networks of internal
      channels are fabricated via an indirect rapid prototyping technique. To obtain
      the scaffolds, two drying methods, namely critical point drying and freeze-drying
      were investigated. The latter was found to be a more suitable process as it
      induced less shrinkage and reproduced the design morphology accurately. The
      resulting scaffold contained internal hollow channels with porous foam-like
      structure occupying the surrounding volume. The mean diameter of the pores was
      180 +/- 60 microm and the channels diameter obtained was measured as 437 +/- 100
      microm. The channels were defined and strengthened by a layer of skin due to the
      process of freeze-drying. These networks of internal channels serve to enhance
      the mass transport rate through the scaffold and help to increase the depth of
      cells penetration in the scaffold.

PMID- 17183565
TI  - Evaluation of DBM/AM composite as a graft substitute for posterolateral lumbar
      fusion.
AB  - Demineralized bone matrix (DBM) has been investigated as a bone graft substitute
      for spinal fusion with less morbidity. Various carriers have been added to DBM to
      enhance its handling characteristics. This study investigates the spinal fusion
      induced by a composite of DBM and acellular dermal matrix (AM) in comparison with
      autologous bone in an athymic rat spinal fusion model. Single-level
      intertransverse process fusions were performed in 60 athymic nude rats grafted
      with 2 mL/kg of DBM/AM composite, AM alone, or autologous bone. Fusion was
      assessed at 6 weeks by radiography, manual palpation, and histology. At 6 weeks,
      70% of the animals from the DBM/AM composite group exhibited complete spine
      fusion, whereas 35% from the autologous bone group and 20% from AM group showed
      bridging with some gaps. The DBM/AM composite induced a significantly higher
      fusion rate than both the autologous bone and AM groups (p < 0.001) in all
      measured parameters. The current study demonstrated that using DBM/AM composite
      can have more robust fusion than autologous bone at 6 weeks in an athymic rat
      spinal fusion model.

PMID- 17183566
TI  - Role of indenter material and size in veneer failure of brittle layer structures.
AB  - The roles of indenter material and size in the failure of brittle veneer layers
      in all-ceramic crown-like structures are studied. Glass veneer layers 1 mm thick
      bonded to alumina layers 0.5 mm thick on polycarbonate bases (representative of
      porcelain/ceramic-core/dentin) are subject to cyclic contact loading with
      spherical indenters in water (representative of occlusal biting environment). Two
      indenter materials-glass and tungsten carbide-and three indenter radii-1.6, 5.0,
      and 12.5 mm-are investigated in the tests. A video camera is used to follow the
      near-contact initiation and subsequent downward propagation of cone cracks
      through the veneer layer to the core interface, at which point the specimen is
      considered to have failed. Both indenter material and indenter radius have some
      effect on the critical loads to initiate cracks within the local Hertzian contact
      field, but the influence of modulus is weaker. The critical loads to take the
      veneer to failure are relatively insensitive to either of these indenter
      variables, since the bulk of the cone crack propagation takes place in the
      contact far field. Clinical implications of the results are considered, including
      the issue of single-cycle overload versus low-load cyclic fatigue and changes in
      fracture mode with loading conditions.

PMID- 17183567
TI  - National evaluation of US newborn screening system components.
AB  - Newborn screening has existed as a state-based public health service since the
      early 1960s. Every state and most territorial jurisdictions have comprehensive
      newborn screening programs in place, but in the United States a national newborn
      screening policy does not exist. This results in different administrative
      infrastructures, screening requirements, laboratory and follow-up services,
      medical management approaches, and related activities across the country. Federal
      initiatives and support have contributed to limited evaluations of various
      aspects of individual newborn screening programs at the national level, but
      funding is an issue. The national evaluation strategies have taken various forms,
      all with the intent of improving the screening system through review of actions
      taken and suggestions for future improvements. While participation in the
      national evaluation effort for newborn screening laboratory practices includes
      all US programs, and this has aided in improving quality and harmonizing
      protocols, other national evaluation activities have been only moderately
      successful. National data reporting of quality indicators for various program
      elements must be comprehensive and timely, and the elements must be universally
      accepted in order to meet the evaluation and improvement needs of the national
      newborn screening system. A comprehensive real time national evaluation activity
      will likely require additional resources and enforcement incentives. Limited
      federal actions through grant incentives and selected reporting requirements
      provide a possible means of stimulating programs to participate in national
      harmonization efforts.

PMID- 17183568
TI  - The clinical aspects of newborn screening: importance of newborn screening follow
      up.
AB  - The aim of newborn screening is to identify presymptomatic healthy infants that
      will develop significant metabolic or endocrine derangements if left undiagnosed
      and untreated. The goal of ultimately reducing or eliminating irreversible
      sequelae is reached by maximizing test sensitivity of the primary newborn
      screening that measures specific analytes by a number of methodologies.
      Differentiation of true from false negatives is accomplished by the test
      specificity. This review discusses disorders for which, in general, there are
      available therapies and that are detected by routine and expanded newborn
      screening. Recommendations are presented for evaluation by a primary care
      physician, with confirmation by a metabolic or endocrinology specialist.
      Disorders are organized in tabular format by class of pathway or analyte, with
      attention to typical clinical presentations, confirmatory biochemical and
      molecular tests, and therapies. There are numerous challenges in clinical follow
      up, including diagnosis and appropriate understanding of the consequences of the
      disorders. The data required to meet these challenges can be acquired only by
      large scale longitudinal comprehensive studies of outcome in children identified
      by newborn screening. Only with such data can newborn screening fully serve
      families.

PMID- 17183569
TI  - Changing perspectives on the benefits of newborn screening.
AB  - The likelihood of benefit is fundamental to decision making about newborn
      screening. But benefit is construed in different ways by different stakeholders.
      This article begins with a review of benefit as considered historically by
      various expert panels and organizations. We then show how 78 conditions fared
      when experts recently rated them on benefit using a scoring system recommended by
      a task force of the American College of Medical Genetics. Finally, we analyze how
      benefit is reflected in the public comments submitted in response to the ACMG
      report. Results show that benefit has been and remains a core consideration for
      screening decisions. Historically the focus has been on improved physical health
      as a result of medical treatment; however, in only 4 of the 78 conditions rated
      does newborn screening prevent all negative consequences. In fact the majority of
      both core conditions (51.7%) and secondary targets (87.5%) recommended in the
      ACMG report were rated as having treatments that prevented only some negative
      consequences. All conditions rated had perceived benefits for family and society,
      but currently no conditions are screened on the basis of family or societal
      benefits alone. No agreed-upon threshold exists for what would be considered
      meaningful benefit, and stakeholder groups differ in their perceptions of
      benefit. We conclude by suggesting several key research studies needed to further
      inform public policy.

PMID- 17183570
TI  - Pilot programs in newborn screening.
AB  - The term "pilot study" has been used over the years to describe the evaluation of
      the many elements involved in deciding whether a proposed condition should be
      added to a newborn screening (NBS) panel, and until recently, was unilaterally
      used to describe the evaluation of the assay to be used before the condition was
      officially adopted by a state for its newborn screening panel. Since Guthrie's
      introduction of screening for PKU, each time a new condition was added to the
      panel, the screening assay itself was validated through a population-based trial,
      in which the test was performed with de-identified samples to avoid association
      between the test result and the infant. This is considered by the laboratory as
      the "pilot phase" of adding a new condition. To advance the science of NBS,
      especially to accommodate new technologies that may provide new types of
      information (genetic versus physiological) for each new condition, pilot programs
      are essential. Involvement of the clinical community serves to improve these
      evaluations and provides the needed clinical validation of decisions made as a
      result of it. This paper describes the historical context of pilot programs in
      population-based NBS that utilize laboratory-based markers as indicators of
      concern; specifically, three applications that demonstrate different approaches
      to the use of pilots in adding conditions to a NBS panel are described.

PMID- 17183571
TI  - Advisory committee on heritable disorders and genetic diseases in newborns and
      children.

PMID- 17183572
TI  - Current status of newborn screening: decision-making about the conditions to
      include in screening programs.
AB  - Newborn screening is considered a highly successful public health program that
      has resulted in the reduction of mortality, mental retardation, and other serious
      disabilities in thousands of children since the introduction of screening for
      phenylketonuria (PKU) in the 1960s. Programs are based in state public health
      departments such that each state independently reaches decisions as to which
      conditions should be mandated for inclusion in programs, leading to considerable
      variability among the states as to what is being screened. New technologies and
      knowledge of the genetics of many conditions have greatly expanded the number of
      conditions with potential for inclusion in newborn screening.

PMID- 17183573
TI  - Making the case for objective performance metrics in newborn screening by tandem
      mass spectrometry.
AB  - The expansion of newborn screening programs to include multiplex testing by
      tandem mass spectrometry requires understanding and close monitoring of
      performance metrics. This is not done consistently because of lack of defined
      targets, and interlaboratory comparison is almost nonexistent. Between July 2004
      and April 2006 (N=176,185 cases), the overall performance metrics of the
      Minnesota program, limited to MS/MS testing, were as follows: detection rate
      1:1,816, positive predictive value 37% (54% in 2006 till date), and false
      positive rate 0.09%. The repeat rate and the proportion of cases with abnormal
      findings actually been reported are new metrics proposed here as an objective
      mean to express the overall noise in a program, where noise is defined as the
      total number of abnormal results obtained using a given set of cut-off values. On
      the basis of our experience, we propose the following targets as evidence of
      adequate analytical and postanalytical performance: detection rate 1:3,000 or
      higher, positive predictive value>20%, and false positive rate<0.3%.

PMID- 17183574
TI  - Introduction: newborn screening.

PMID- 17183575
TI  - NICHD research initiative in newborn screening.
AB  - Recent changes in genetics research have created new opportunities to improve the
      scope and quality of newborn screening services. Changes in newborn screening
      should be supported and directed by an organized program of research. The NICHD
      Research Initiative in Newborn Screening includes the development of systematic
      methods to identify additional conditions appropriate for newborn screening;
      development and testing innovative interventions and treatments to improve
      outcomes; education of the provider workforce; development and implementation of
      appropriate information and communication systems for parents and providers; and,
      sponsoring an ongoing program of research and research training. Future needs
      will include the development of a national translational research infrastructure,
      prevention research and research into behavioral and social sciences issues. The
      NICHD Research Initiative in Newborn Screening is expected to be an ongoing and
      vital initiative that adapts itself to new scientific findings, technological
      developments, changes in the public and personal health care system, and our
      evolving understanding of the needs of affected individuals, families and the
      community.

PMID- 17183576
TI  - Universal newborn screening and adverse medical outcomes: a historical note.
AB  - Universal newborn screening programs for metabolic disorders are typically
      described as a triumph of medicine and public policy in the US over the last 50
      years. Advances in science and technology, including the Human Genome Project,
      offer the opportunity to expand universal newborn screening programs to include
      many additional metabolic and genetic conditions. Although the benefits of such
      screening programs appear to outweigh their costs, some critics have claimed that
      historical examples of inadvertent harm ensuing from false-positive screening
      results and subsequent inappropriate medical treatment should make us wary of
      expanding universal newborn screening. In this essay, we report the results of a
      review of the published literature to assess whether the extension of screening
      from at risk populations to all newborns led to substantial morbidity and
      mortality from misguided medical treatment. We provide a historical overview of
      universal newborn screening programs in the United States, and then focus on six
      early NBS programs: congenital hypothyroidism, phenylketonuria, congenital
      adrenal hyperplasia, galactosemia, sickle cell disease, and maple syrup urine
      disease. Our comprehensive search of published sources did not reveal a
      widespread problem of harm ensuing from medical treatment of children with false
      positive screening test results.

PMID- 17183577
TI  - Critical role of the March of Dimes in the expansion of newborn screening.
AB  - Expansion of newborn screening (NBS) has been driven primarily by a combination
      of advances in technology and medical treatment, and the sustained advocacy
      efforts of consumers and voluntary health organizations. The longstanding
      leadership of the March of Dimes has been credited by many as a critical factor
      in the expansion and improvement of state NBS programs. From the historic vantage
      point of four decades of March of Dimes involvement with newborn screening, this
      report reviews the unique origin of the first newborn screening test, and
      identifies from this point of origin several of the elements which still define
      the evolution of advocacy for NBS today. It also documents activities at the
      federal level and in seven states that have lead to expanded screening for
      newborns. Advances in NBS technology and medical treatment have informed policy
      development. Mobilization of volunteers and focused advocacy activities have
      brought about expansion of screening opportunities for newborns across the United
      States. But more work is needed. Continued application of the effective
      strategies identified in this report will help assure that all families have the
      best possible chance of assuring that their newborns do not have to suffer the
      complications of conditions that we know can be treated effectively.

PMID- 17183578
TI  - The regional genetic and newborn screening service collaboratives: the first two
      years.
AB  - Newborn screening and genetic technologies are expanding and changing rapidly,
      increasing the demand for genetic specialty services. Because of the scarcity and
      geographic maldistribution of genetic specialty services, access to these
      services is a critical issue. This article discusses some of the efforts
      initiated by the Maternal and Child Health Bureau of the Health Resources and
      Services Administration, particularly the establishment of regional genetic and
      newborn screening collaboratives to improve access to these services and
      expertise.

PMID- 17183579
TI  - The role of National Library of Medicine web sites in newborn screening
      education.
AB  - Expanded newborn screening programs and subsequent detection of rare genetic
      disorders challenge parents and their medical providers to learn about the
      treatment and management of these disorders. Many people seek medical information
      on the Internet but may encounter requests for registration or fees, or find that
      resources are out of date, difficult to understand, or buried in advertisements.
      The U.S. National Library of Medicine (NLM), a component of the National
      Institutes of Health, provides web-based resources that address the challenges of
      newborn screening education. These resources include MedlinePlus, Genetics Home
      Reference, ClinicalTrials.gov, and PubMed. NLM websites are not commercial, do
      not require registration or fees, and provide varied levels of information for a
      continuum of audiences from low-literacy consumers to health professionals. Using
      phenylketonuria as an example, this study describes the information that parents
      and their medical providers can find through NLM resources. NLM has embraced the
      digital age and provides the public with reliable, accurate, and up-to-date
      educational materials.

PMID- 17183580
TI  - Hydroxyapatite moldable formulation using natural rubber latex as binder.
AB  - A simple but efficient processing method for shaping intricate bioceramic green
      bodies has been developed by using natural rubber latex as binder. Different
      shapes of hydroxyapatite Ca10(PO4)6(OH)2 (HAP) were molded from a composite
      formulation containing wet precipitated HAP, natural rubber latex (NRL), and a
      stabilizer. On controlled heat treatment followed by sintering, dense shapes of
      HAP contours were obtained. The thermal degradation profile of HAP-NRL composites
      shows that NRL degrades slowly without any abrupt exotherm. The results of energy
      dispersive X-ray analysis together with inductively coupled plasma (ICP) analysis
      indicate that the inorganic residue of NRL does not contain any heavy element.
      The sintered density of the samples increased with increased HAP content in the
      formulation and percentage shrinkage reduced accordingly. On varying the HAP
      content in the formulation from 35 to 95 wt %, the compositions with 85, 90, 92,
      and 95 wt % HAP showed better flexural strength in the range 40-54 MPa and a
      flexural modulus value in the range 36-50 GPa. The fracture morphology, as
      observed by the scanning electron microscope confirms that with increased HAP
      content in the formulation the sample microstructure attains higher uniformity.
      The Vickers microhardness for the samples sintered at two different temperatures
      (1150 and 1250 degrees C) showed that hardness increases with increase in the
      sintering temperature with a maximum for the highest HAP loaded formulation.

PMID- 17183581
TI  - Comparison of structure, strength and cytocompatibility of a fibrin matrix
      supplemented either with tranexamic acid or aprotinin.
AB  - Fibrin sealants are used as hemostats, sealants, tissue adhesives, and as matrix
      for substances/cells in a number of surgical and tissue engineering procedures.
      Main characteristics of fibrin are high tensile strength, adhesive strength,
      biocompatibility, and resorption. A major adverse event would be premature fibrin
      lysis and recurrent bleeding. This must be prevented by fibrinolysis inhibitors.
      The most common fibrinolysis inhibitors used are aprotinin and tranexamic acid (t
      AMCA). Comparison of commercially available fibrin sealants utilizing aprotinin
      or t-AMCA revealed a lower sealing efficacy in an in vivo lung resection model
      for a t-AMCA containing product. Therefore, we compared the influence of t-AMCA
      and aprotinin on structure, mechanical properties, and cytocompatibility of a
      fibrin matrix. In our experiments, we found that substitution of aprotinin with t
      AMCA reduced the tensile strength and formation of fibrin fibers and affected
      viability of a fibroblast cell-line. In conclusion, t-AMCA negatively affects
      physical and biological properties of fibrin relevant for clinical application as
      well as tissue regeneration.

PMID- 17183582
TI  - Longitudinal evaluation of early and late anthracycline cardiotoxicity in
      children with AML.
AB  - BACKGROUND: Anthracyclines are effective antineoplastic drugs in acute
      myelogenous leukemia (AML). However, their use is limited by cardiomyopathy,
      which occurs in children already at cumulative doses of 300 mg/m(2) (given as
      daunorubicin equivalent). PROCEDURE: To evaluate anthracycline-associated
      cardiomyopathy in pediatric AML-patients, the incidence of early and late (>1
      year after intensive AML chemotherapy) clinical and subclinical cardiotoxicity
      was analyzed out of a total of 1,207 patients <18 years treated between 1993 and
      2003 in trials AML-BFM93/98: 1,010 protocol patients with de novo AML, 121 with
      Down syndrome (DS)-AML, and 76 with secondary AML. The cumulative dose of
      anthracyclines was generally risk-adapted: 300-450 mg/m(2) using 1-4-hr infusions
      of anthracyclines with the assumed lowest cardiotoxic potential. Eight hundred
      eighty-five patients (73%) were eligible for the analysis of early and 547 (45%)
      of late cardiotoxicity (1,399 follow-up data). RESULTS: Thirty-eight patients
      (4.3%), including 3 DS-AML and 1 secondary AML, suffered from early
      cardiomyopathy. After 5 years, four patients showed temporarily or persistently a
      reduced shortening fraction, which led to death in one DS-AML patient. Including
      these 4 patients, late cardiomyopathy was seen in 16 patients (cumulative
      incidence after 11 years: 5% +/- 1%). Nine patients (2.5 +/- 1%) showed clinical
      symptoms, five of them had persistent abnormal shortening fraction. Late
      subclinical cardiomyopathy occurred temporarily in seven patients. Late clinical
      cardiomyopathy mainly affected patients with a second anthracycline therapy
      (secondary malignancy) and those with early cardiotoxicity. CONCLUSION: In spite
      of a highly intensive and effective treatment, the frequency of anthracycline
      associated cardiomyopathy was low in the AML-BFM studies.

PMID- 17183583
TI  - MRI findings in Shwachman diamond syndrome.
AB  - Shwachman Diamond Syndrome (SDS) is a rare congenital disorder characterized by
      pancreatic insufficiency, bone marrow dysfunction, and skeletal changes. Because
      of the heterogeneous clinical presentation and the limits of laboratory tests
      that assess pancreatic insufficiency, the diagnosis of SDS can be challenging.
      Pancreatic lipomatosis, a typical feature of this syndrome, is also difficult to
      assess by direct tissue sampling. In these circumstances, magnetic resonance
      imaging (MRI) provides a readily available, noninvasive tool to evaluate the
      pancreatic fat content. We report a case of a 12-month-old male in which
      abdominal MRI was used to confirm the clinical diagnosis of SDS.

PMID- 17183584
TI  - Exposure of neural crest cells to elevated glucose leads to congenital heart
      defects, an effect that can be prevented by N-acetylcysteine.
AB  - BACKGROUND: Diabetes mellitus during pregnancy increases the risk for congenital
      heart disease in the offspring. The majority of the cardiovascular malformations
      occur in the outflow tract and pharyngeal arch arteries, where neural crest cells
      are essential for normal development. We studied the effects of specific exposure
      of neural crest cells to elevated glucose on heart development. Antioxidants
      reduce the damaging effect of glucose on neural crest cells in vitro; therefore,
      we investigated the effect of supplementing N-acetylcysteine in vivo. METHODS:
      Cardiac neural crest of HH 8-12 chicken embryos was directly exposed by a single
      injection in the neural tube with 30 mM D-glucose (or 30 mM L-glucose as a
      control). To examine the effect of a reduction in oxidative stress, we added 2 mM
      N-acetylcysteine to the injected D-glucose. RESULTS: Exposure of neural crest
      cells to elevated D-glucose-induced congenital heart malformations in 82% of the
      embryos. In the embryos injected with L-glucose, only 9% developed a heart
      malformation. As expected, all malformations were located in the outflow tract
      and pharyngeal arch arteries. The frequency of heart malformations decreased from
      82% to 27% when 2 mM N-acetylcysteine was added to the injected D-glucose.
      CONCLUSIONS: These data are the first to confirm that the vulnerability of neural
      crest cells to elevated glucose induces congenital heart malformations. The fact
      that N-acetylcysteine limits the teratogenicity of glucose implies that its
      damaging effect is mediated by an increase of oxidative stress in the neural
      crest cells.

PMID- 17183586
TI  - Adult index patient with Currarino syndrome due to a novel HLXB9 mutation,
      c.336dupG (p.P113fsX224), presenting with Hirschsprung's disease, cephalgia, and
      lumbodynia.
AB  - BACKGROUND: The symptom triad of autosomal dominant Currarino syndrome (CS; MIM
      #176450) consists of anorectal malformation, a sacral bone defect, and presacral
      masses. Mutations in the homeoboxHLXB9 gene have already been described in a
      subset of sacrococcygeal anomalies characterized by partial sacral agenesis.
      CASE: We report a 28-year-old male patient with Currarino syndrome due to a
      heterozygous novel frame-shift mutation c.336dupG (p.P113fsX224) in the
      homeoboxHLXB9 gene. CONCLUSIONS: Molecular diagnostics may be helpful in cases of
      Hirschsprung's disease accompanied by other symptoms suggestive for Currarino
      syndrome, since it can lead to major complications such as perianal sepsis,
      meningitis, and malignant transformation.

PMID- 17183585
TI  - Platelet-derived growth factor C plays a role in the branchial arch malformations
      induced by retinoic acid.
AB  - BACKGROUND: All-trans-retinoic acid (RA) can produce branchial arch abnormalities
      in postimplantation rodent embryos cultured in vitro. Platelet-derived growth
      factor C (PDGF-C) was recently identified as a member of the PDGF ligand family.
      Many members of the PDGF family are essential for branchial arch morphogenesis
      and can be regulated by RA. The roles of PDGF-C in branchial arch malformations
      induced by RA and possible mechanisms were investigated. METHODS: In whole embryo
      culture (WEC), mouse embryos were exposed to RA at 0, 0.1, 0.4, 1.0, or 10.0
      microM, PDGF-C at 25, 50, or 75 ng/mL, or PDGF-C at 25, 50, or 75 ng/mL
      containing 0.4 microM RA. After 48 h of culture, mouse embryos were examined for
      dysmorphogenesis, and whole-mount immunohistochemistry was applied to PDGF-C. In
      explant cultures, explants were exposed to the same doses of RA and PDGF-C as
      WEC. Semiquantitative RT-PCR, zymography, and reverse zymography were used to
      evaluate the expressions and activities of matrix metalloproteinase (MMP)-2, MMP
      14, and tissue inhibitor of metalloproteinase (TIMP)-2. RESULTS: PDGF-C was
      reduced by RA, and exogenous PDGF-C rescued the branchial arch malformations
      induced by RA. Moreover, PDGF-C prevented RA-induced inhibition of the migratory
      ability of mesenchymal cells in the first branchial arch, by regulating the
      expressions of MMP-2, MMP-14, and TIPM-2. CONCLUSIONS: Our results suggest that
      RA exposure reduces the expression of PDGF-C. The branchial arch malformations
      resulting from fetal RA exposure are caused at least partially by loss of PDGF-C
      and subsequent misregulations of the expressions of MMP-2, MMP-14, and TIMP-2.

PMID- 17183587
TI  - Patterns of severe abdominal wall defects: insights into pathogenesis,
      delineation, and nomenclature.
AB  - BACKGROUND: During the last decade, descriptions of malformation complexes
      involving an abdominal wall defect (AWD) have repeatedly appeared in the
      literature, and there has been frequent confusion regarding nomenclature,
      definitions, and delineations. The aims of this work were to evaluate possible
      embryological relationships among AWD cases, review the related nomenclature,
      identify patterns involving AWDs, and stress the importance of complete clinical
      descriptions. METHODS Cases diagnosed as AWD complexes were selected from live-
      and stillborn infants of the Hospital Materno Infantil Ramon Sarda, Buenos Aires,
      and from the Laboratory of Perinatal Pathology, Buenos Aires, Argentina. They
      were sorted by the location of the AWD, the umbilical cord length, and the
      presence or absence of a persistent cloaca. The findings in 26 cases were
      described, according to proposed definitions. RESULTS: Three patterns could be
      identified: 1) the AWD involving the umbilical ring, a persistent or exstrophic
      cloaca, and a spinal cord anomaly; 2) the AWD extending laterally to the
      umbilical ring, severe unilateral limb defects, and same-sided agenesis of
      abdominal organs; and 3) the AWD not involving the umbilical ring, clefts,
      exencephaly, and amputations. Furthermore, overlapping among these patterns was
      observed, and possible involved mechanisms are discussed. CONCLUSIONS: The
      observed overlapping among patterns suggested that malformation complexes
      involving AWDs might not be independent conditions but rather belong to a common
      and broader spectrum of anomalies. Complete clinical descriptions, the avoidance
      of synonyms and generalizations, and strictly defined inclusion criteria are
      proposed for a better understanding of pathogenetic pathways in, and
      relationships among, AWD complexes.

PMID- 17183588
TI  - Reduced aggression in mice lacking GABA transporter subtype 1.
AB  - Dysregulation of the brain GABAergic system has been implicated in the
      pathophysiology of violence and aggression. As a key regulator of central
      GABAergic activity, dysfunction of the GABA transporter subtype 1 (GAT1)
      represents a potential mechanism mediating pathologic aggression. We provide
      evidence that GAT1-/- mice and GAT1+/- mice exhibit lower aggressive behavior
      both in home cage resident-intruder test and neutral arena resident-intruder
      test, compared to wild-type mice (GAT1+/+). The pharmacologic effects of the GAT1
      inhibitor, tiagabine and the GABA(A) receptor antagonist, bicuculline have been
      assessed in GAT1+/+ mice: tiagabine inhibits attacks but bicuculline induces
      attacks. Compared to GAT1+/- and +/+ mice, the GAT1-/- mice displayed a normal
      circadian pattern of home cage activity, but more activity overall. Meanwhile,
      reduced testosterone concentration was found in GAT1-/- mice compared to GAT1+/+
      mice but not in GAT1+/+ mice treated with tiagabine, suggesting that testosterone
      is not directly involved in GAT1 mediated aggressive behavior regulation. These
      results showed that GAT1 is an important target involved in the regulation of
      aggressive behavior in mice, and long-term dysfunction of GAT1 may also result in
      the alteration of testosterone secretion.

PMID- 17183589
TI  - Mitogen-associated protein kinase- and protein kinase A-dependent regulation of
      rhodopsin promoter expression in zebrafish rod photoreceptor cells.
AB  - Mitogen-associated protein kinase (MAPK)- and protein kinase A (PKA)-dependent
      signal transductions play important roles in the regulation of gene expression.
      Both MAPK and PKA pathways can be activated by light exposure. In this study, we
      investigated the effect of light on MAPK and PKA signal transduction and their
      roles in the regulation of rhodopsin promoter expression by using transgenic
      zebrafish [Tg(rhod::GFP)]. The Tg(rhod::GFP) fish express short half-life GFP
      that is under the transcriptional control of the zebrafish rhodopsin promoter and
      can therefore be used for in vivo studies of rhodopsin gene transcription in live
      cells. Blue light plays a role in the regulation of rhodopsin promoter expression
      via an MAPK-mediated signal transduction cascade. Blue light excites
      cryptochromes (CRY), which activate the downstream PKC-dependent MAPK signal
      pathway. White light, on the other hand, regulates rhodopsin promoter expression
      via a G-protein-coupled cAMP-dependent PKA pathway. White light promotes dopamine
      release in the retina, which activates dopamine receptors and the downstream PKA
      pathway. Blocking MAPK signaling diminishes the blue light-induced increases in
      rhodopsin promoter expression, but this treatment has no effect on white light
      mediated rhodopsin promoter expression. Conversely, blocking the PKA pathway
      diminishes the white light-induced rhodopsin promoter expression but does not
      affect rhodopsin promoter expression regulated by blue light. Together, the data
      suggest that MAPK and PKA regulate rhodopsin transcription through parallel
      signal transduction pathways.

PMID- 17183591
TI  - The crystallization behavior of proline and its role in asymmetric
      organocatalysis.

PMID- 17183590
TI  - Antiapoptotic mechanism of cannabinoid receptor 2 agonist on cisplatin-induced
      apoptosis in the HEI-OC1 auditory cell line.
AB  - Cisplatin is a highly effective chemotherapeutic agent but with significant
      ototoxic side effects. Apoptosis is an important mechanism of cochlear hair cell
      loss following exposure to an ototoxic level of cisplatin. The present study
      investigated the effects of the cannabinoid receptor 2 (CB2) ligand JWH-015 on
      cisplatin-induced apoptosis. CB2 mRNA was constitutively expressed in the
      auditory cell line HEI-OC1. By using MTT assay, DNA fragmentation, and FACS
      analysis, we demonstrated that apoptosis induced by cisplatin was inhibited by
      treatment with JWH-015 in a dose-dependent manner. Activation of caspase-3,
      caspase-8, and caspase-9 was detected after treatment with cisplatin, and the
      cleavage of poly-(ADP)-ribose polymerase (PARP) was observed within cisplatin
      treated HEI-OC1 cells. JWH-015 inhibited the activation of caspase-3, caspase-8,
      and caspase-9; cleavage of PARP; and release of cytochrome c. JWH-015 also
      inhibited the apoptosis through activation of the extracellular signal-regulated
      kinase pathway. Finally, JWH-015 inhibited cisplatin-induced reactive oxygen
      species and tumor necrosis factor-alpha production. Collectively, these findings
      show that blocking a critical step in apoptosis by using JWH-015 may be a useful
      strategy to prevent harmful side effects of cisplatin ototoxicity in patients
      having to undergo chemotherapy.

PMID- 17183592
TI  - A method for patterning multiple types of cells by using electrochemical
      desorption of self-assembled monolayers within microfluidic channels.

PMID- 17183593
TI  - Near-monodisperse tetrahedral rhodium nanoparticles on charcoal: the shape
      dependent catalytic hydrogenation of arenes.

PMID- 17183595
TI  - Modifications in the bradykinin main chain are not necessary for antagonistic
      activity in rat blood pressure assay.
AB  - Previous studies demonstrated that the presence of a bulky acyl substituent at
      the N-terminus of B(2) antagonists significantly influenced the interaction of
      the peptide with B(2) receptors, thus increasing potency in the blood pressure
      test. Reported results also suggested that even minor changes in the structure of
      analogues might be of importance in designing more potent B(2) antagonists. On
      the other hand, it was learned that the effects of acylation might vary
      substantially with the chemical character of the acyl group. It seemed that
      either the positive or the negative charge on the N-terminal acyl group
      influenced the activity of the analogues because a suppressed antagonistic
      potency due to these modifications was observed. Bearing all these findings in
      mind, it was decided to check how N-terminal acylation would affect the
      pharmacological activity of bradykinin. Of the many acylating agents tested
      previously on B(2) antagonists, it was decided to use acridin-9-ylacetic acid
      (Ana) and anthracen-9-ylacetic acid (Ata). The potencies of the analogues were
      assessed by their ability to inhibit vasodepressor response of exogenous BK in
      conscious rats and by their ability to inhibit the contractions of isolated rat
      uterus evoked by BK.

PMID- 17183596
TI  - Formation of fibril structures in polymerizable, rod-coil-oligomer-modified epoxy
      networks.
AB  - This paper describes the in situ preparation of fibrils in epoxy networks in
      which the fibril-like structures are cured polymerizable rod-coil oligomers. The
      epoxy-terminated alpha,omega-modified PEO oligomers, which are ABA rod-coil-rod
      oligomers with a poly(ethylene oxide) coil unit and two aromatic azomethine
      liquid-crystalline rod units, were synthesized and then further blended with an
      epoxy precursor. Uniform nanoscale columnar structures were observed in the neat
      rod-coil oligomers as well as in the crosslinked liquid-crystalline state. During
      the curing of the blends, the supramolecular nanoscale columnar structures of the
      rod-coil oligomers are transformed into polymeric fibrils where the epoxy
      functional end groups have co-reacted with epoxy precursors to form a crosslinked
      network.

PMID- 17183594
TI  - Amphiphilic NO-donor antioxidants.
AB  - Models of amphiphilic NO-donor antioxidants 24-26 were designed and synthesized.
      The products were obtained by linking a lipophilic tail (C(6), C(8), C(10)) with
      a polar head constituted by the 2,6-dimethoxyphenol antioxidant joined to the NO
      donor 3-furoxancarboxamide substructure through a bridge containing a quaternary
      ammonium group. Compound 23, containing the shortest C(2)-alkyl chain, was also
      studied as a reference. The antioxidant properties (TBARS and LDL oxidation
      assays) and the vasodilator properties of the compounds were studied in vitro.
      The ability of these products to interact with phospholipid vesicles was also
      investigated by NMR techniques. The results indicate that both activities are
      modulated by the ability of the compounds to accumulate on phospholipid layers.

PMID- 17183597
TI  - On the nature of DNA-duplex stability.
AB  - The unwinding free energy of 128 DNA octamers was correlated with the sum of
      interaction energies among DNA bases and their solvation energies. The former
      energies were determined by using the recently developed density functional
      theory procedure augmented by London dispersion energy (RI-DFT-D) that provides
      accurate hydrogen-bonding and stacking energies highly comparable with
      CCSD(T)/complete basis set limit benchmark data. Efficient tight-binding DFT
      covering dispersion energy was also used and yielded satisfactory results. The
      latter method can be used for extended systems. The solvation energy was
      determined by using a C-PCM continuum solvent at HF level calculations. Various
      models were adopted to correlate theoretical energies with experimental unwinding
      free energies. Unless all energy components (hydrogen-bonding, intra- and
      interstrand-stacking, and solvation energies) were included and weighted
      individually, no satisfactory correlation resulted. The most advanced model
      yielded very close correlation (RMSE=0.32 kcal mol(-1)) fully comparable with the
      entirely empirical correlation introduced in the original paper. Analysis of the
      theoretical results shows the importance of inter- and intramolecular stacking
      energies, and especially the latter term plays a key role in determining DNA
      duplex stabilization.

PMID- 17183598
TI  - A valuable, inexpensive Cui/n-heterocyclic carbene catalyst for the selective
      diboration of styrene.
AB  - The complexes [Cu(NHC)(NCMe)]BF4 (NHC=N-heterocyclic ligand), with
      bis(catecholato)diboron (B2(cat)2) as the boron source, efficiently catalyze the
      diboration of styrene with very high degrees of conversion. With the appropriate
      NHC ligand, the reaction proceeds quantitatively toward the diborated derivative
      PhCH(Bcat)--CH2(Bcat). The [styrene]/[B2(cat)2] ratio also has a strong effect on
      the selectivity: the use of an excess of styrene allows modification of the
      selectivity toward the formation solely of the monoborated derivative, PhCH2-
      CH2(Bcat). DFT calculations suggest that no oxidative addition processes take
      place at copper, but that intermediates containing coordinated sigma-bonds are
      involved in the catalytic cycle.

PMID- 17183599
TI  - One-step synthesis of large-aspect-ratio single-crystalline gold nanorods by
      using CTPAB and CTBAB surfactants.
AB  - Gold nanorods were prepared in high yields by using a one-step seed-mediated
      process in aqueous cetyltripropylammonium bromide (CTPAB) and
      cetyltributylammonium bromide (CTBAB) solutions in the presence of silver
      nitrate. The diameters of the nanorods range from 3 to 11 nm, their lengths are
      in the range of 15 to 350 nm, and their aspect ratios are in the range of 2 to
      70. The diameters of the Au nanorods obtained from one growth batch in CTPAB
      solutions decrease as their lengths increase, and their volumes decrease as the
      aspect ratios increase. The diameters of the Au nanorods obtained from one growth
      batch in CTBAB solutions first decrease and then slightly increase as their
      lengths increase, and their volumes increase as the aspect ratios increase. These
      Au nanorods are single-crystalline and are seen to be oriented in either the
      [100] or [110] direction under transmission electron microscopy imaging,
      irrespective of their sizes. To the best of our knowledge, this is the first
      report of the preparation by using wet-chemistry methods of single-crystalline Au
      nanorods with aspect ratios larger than 15.

PMID- 17183600
TI  - Reversible immobilization and direct electron transfer of cytochrome c on a pH
      sensitive polymer interface.
AB  - A pH-sensitive polymer interface has been used as a matrix for reversible
      immobilization of cytochrome c (Cyt c) on an Au surface through a dip-coating
      process. The pH-sensitive behavior of the polymer brush interface has been
      demonstrated by cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS) measurements. The reversible immobilization and electron
      transfer properties of Cyt c have been investigated by in situ UV/Vis
      spectrophotometry and CV. The results have shown that the poly(acrylic acid)
      (PAA) brush acted as an excellent adsorption matrix and a good accelerant for the
      direct electron transfer of Cyt c, which gave redox peaks with a formal potential
      of 40 mV versus Ag/AgCl in pH 7.6 phosphate buffer solution. The average surface
      coverage of Cyt c on the PAA film was about 1.7 x 10(-10) mol cm(-2), indicating
      a multilayer of Cyt c. The electron-transfer rate constant was calculated to be
      around 0.19 s(-1) according to the CV experiments. The interface was subjected to
      in situ attenuated total internal reflection Fourier-transform infrared (ATR
      FTIR) spectroscopic analysis, in order to further confirm the immobilization of
      Cyt c on the surface. This polymer-protein system may have potential applications
      in the design of biosensors, protein separation, interfacial engineering,
      biomimetics, and so on.

PMID- 17183601
TI  - Tuning the excited-state energy of the organic chromophore in bichromophoric
      systems based on the Ru(II) complexes of tridentate ligands.
AB  - A series of new heteroleptic and homoleptic Ru(II) complexes containing variously
      substituted bis(pyridyl)triazine ligands has been prepared and their absorption
      spectra, redox behaviour and luminescence properties (both in fluid solution at
      room temperature and in a rigid matrix at 77 K) have been investigated. For some
      compounds, X-ray structures have also been determined. The new
      bis(pyridyl)triazines incorporate additional chromophores, such as biphenyl,
      phenanthrene, anthracene and bromoanthracene derivatives, so the Ru(II) species
      can be considered as multichromophoric species. The absorption spectra and redox
      properties of all the metal complexes have been assigned to features belonging to
      specific subunits, thus suggesting that these species can be regarded as
      multicomponent, supramolecular assemblies from an electronic coupling point of
      view. Whereas most of the complexes exhibit luminescence properties that can be
      attributed to metal-to-ligand charge-transfer (MLCT) states involving the metal
      based subunit(s), the species containing the anthryl and, even more, the
      brominated anthryl chromophores exhibit complicated luminescence behaviour. For
      example, 2 d (the anthryl-containing heteroleptic metal compound) exhibits MLCT
      emission at room temperature and emission from the anthracene triplet at 77 K; 2
      e (the bromo-substituted anthryl-containing heteroleptic metal compound) exhibits
      anthryl-based emission at 77 K and MLCT emission at room temperature, but with a
      prolonged lifetime, thus suggesting equilibration between two triplet states that
      belong to different chromophores. The equilibration regime between MLCT and
      aromatic hydrocarbon triplet states is therefore reached by suitable substitution
      on the organic chromophore.

PMID- 17183602
TI  - Kinetic study on the reaction of OH radical with dimethyl sulfide in the absence
      of oxygen.
AB  - A variational transition-state theory calculation for the reaction of OH radical
      with dimethyl sulfide (DMS) in the absence of oxygen is presented. The potential
      energy surface was previously studied and the effects of different levels of
      theory were analyzed. Here we propose a kinetic model for the atmospheric DMS
      oxidation in the absence of oxygen. For the first time, addition of OH to DMS and
      CH(3)SOH elimination channels are connected, and the equilibrium approximation in
      the high-pressure regime is applied to the DMS-OH adduct in the absence of
      oxygen. Both low- and high-pressure limits are considered to analyze the two
      different mechanisms of the H-abstraction channel, and two different kinetic
      approaches are applied to study them. The rate constants for the addition
      elimination and H-abstraction routes are compared and the branching ratios are
      also studied. Tunneling contributions and kinetic isotope effects are analyzed.
      We conclude, in agreement with experimental observations, that in the absence of
      oxygen DMS oxidation takes place via H-abstraction with a branching ratio of 1.0
      at atmospheric temperatures.

PMID- 17183603
TI  - Functionalized metallic carbon nanotube devices for pH sensing.

PMID- 17183604
TI  - Reaction pathways involved in the mechanism of AlIII chelation with caffeic acid:
      catechol and carboxylic functions competition.
AB  - Density functional theory calculations on the AlIII-caffeic acid system are
      carried out to investigate the fixing mechanism of this metal ion to the two
      competing complexing sites in the ligand. This theoretical study was performed to
      explain the complex formation of 1:1 stoichiometry observed in aqueous medium at
      low pH values. Both complexation with the catechol and carboxylic functions are
      envisaged. The reaction pathways for the formation of these two chelates are
      calculated at the B3LYP/6-31G** level of theory. The complexation on the more
      acidic group is relatively straightforward and shows the intermediate formation
      of a monodentate complex followed by a chelation process. The complexation
      reaction pathway with the catechol function is more sophisticated, and several
      pathways are explored. Once more, the formation of a monodentate complex is
      achieved and the most favorable pathway for chelation involves the successive
      steps: 1) coordination of AlIII on the oxygen atom of a hydroxyl group, 2)
      deprotonation of this hydroxyl group, 3) ring closure with the other oxygen atom,
      and 4) deprotonation of the second hydroxyl. From an energetic point of view,
      this second pathway is more favorable. Notably the energy barrier necessary to
      form the chelate is lower for the catechol function than that calculated for the
      carboxylic group. The results of this purely theoretical study are in complete
      agreement with spectroscopic investigations performed on this system.

PMID- 17183605
TI  - A simple algorithm to accelerate the computation of non-bonded interactions in
      cell-based molecular dynamics simulations.
AB  - Cell lists are ubiquitous in molecular dynamics simulations--be it for the direct
      computation of short-range inter-atomic potentials, the short-range direct part
      of a long-range interaction or for the periodic construction of Verlet lists. The
      conventional approach to computing pairwise interactions using cell lists leads
      to a large number of unnecessary interparticle distance calculations. In this
      paper, an algorithm is presented which reduces the number of spurious distance
      calculations by first sorting the particles along the cell pair axis and then
      only interacting two particles if their distance along the axis is smaller than
      the cutoff distance of the interaction. This approach is shown to be more
      efficient than the conventional approach and similar approaches using smaller
      cells.

PMID- 17183606
TI  - Enhanced intra-switch region recombination during immunoglobulin class switch
      recombination in 53BP1-/- B cells.
AB  - Immunoglobulin class switch recombination (CSR) is initiated by activation
      induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in
      single-stranded DNA. U:G mismatches created by AID are processed to produce
      lesions that recruit and activate DNA damage response proteins including Ataxia
      telangiectasia mutated (ATM), histone H2AX, Nijmegen breakage syndrome 1 (Nbs1),
      and p53 binding protein 1 (53BP1). Among these proteins, absence of 53BP1
      produces the most severe impairment of class switching. Here, we demonstrate that
      AID is targeted normally to switch region DNA and that intra-switch region
      recombination is enhanced in 53BP1-/- B cells. In addition, Smicro-Sgamma1 switch
      region junctions cloned from 53BP1-/- B cells show unusual insertions suggestive
      of failed class switching. Our data are consistent with a role for 53BP1 in
      stabilizing the synapsis of switch regions during CSR.

PMID- 17183610
TI  - New vistas on macrophage differentiation and activation.
AB  - Plasticity and heterogeneity are hallmarks of myelomonocytic differentiation and
      polarized activation. Evidence published in this issue of the European Journal of
      Immunology, together with other recent data, add new elements and perspectives to
      the current understanding of mononuclear phagocyte differentiation and activation
      and are discussed in this Commentary.

PMID- 17183612
TI  - FOXP3: not just for regulatory T cells anymore.
AB  - The forkhead family transcription factor FOXP3 has been shown to be critical for
      the development and function of CD4+ CD25+ regulatory T cells. Recently, FOXP3
      expression has been shown to be induced upon activation of human CD4+ T cells. A
      new report in this issue of the European Journal of Immunology shows that
      expression of FOXP3 in activated T cell leads to hyporesponsiveness, but not
      necessarily to acquisition of suppressor function. This finding suggests a new
      role for FOXP3 in human CD4+ T cells: down-modulating responses to TCR-mediated
      stimulation.

PMID- 17183611
TI  - Anti-OX40 stimulation in vivo enhances CD8+ memory T cell survival and
      significantly increases recall responses.
AB  - There is growing evidence that engagement of OX40 (CD134), a member of the TNF
      receptor superfamily, can directly stimulate antigen-specific CD8+ T cells. It
      has been shown that CD8+ T cells express OX40 following activation, but the
      response of antigen-specific CD8+ T cells to OX40 stimulation has not been fully
      characterized. We utilized an antigen-specific transgenic CD8+ T cell model (OT
      I) to determine if OX40 engagement can boost the generation of antigen-specific
      CD8+ T cell memory. Our results demonstrate that enhanced OX40 costimulation, via
      an agonist anti-OX40 antibody, increases CD25 and phospho-Akt expression on the
      antigen-specific CD8+ T cells and significantly increases the generation of long
      lived antigen-specific CD8+ memory T cells. The increased numbers of memory CD8+
      T cells generated via anti-OX40 treatment still required the presence of CD4+ T
      cells for their long-term maintenance in vivo. In addition, anti-OX40
      costimulation greatly enhanced antigen-specific CD8+ T cell recall responses.
      These data show that OX40 engagement in vivo increases the number of antigen
      specific CD8+ memory T cells surviving after antigen challenge and has
      implications for the development of more potent vaccines against pathogens and
      cancer.

PMID- 17183613
TI  - Symmetric peripheral gangrene as an emerging manifestation of polyarteritis
      nodosa.

PMID- 17183614
TI  - The Quality of My Life questionnaire: the minimal clinically important difference
      for pediatric rheumatology patients.
AB  - OBJECTIVE: To determine parent-child agreement for the Quality of My Life (QoML)
      questionnaire. To establish construct validity of the QoML questionnaire. To
      determine the minimal clinically important difference (MCID) for the Quality of
      Life (QOL) and Health-Related Quality of Life (HRQOL) scales. METHODS: A total of
      136 families of children with inflammatory arthritis were interviewed. The QoML
      questionnaire was completed for the child's current state of health, and under 2
      hypothetical scenarios, where (1) there is a hypothetical small improvement, and
      (2) there is a hypothetical small deterioration in health. The differences
      between the original QOL and HRQOL scores and hypothetical improvement and
      deterioration scores, respectively, were calculated to give MCID scores. RESULTS:
      In total, 131 families completed the questionnaires. Intraclass correlation
      coefficients for parent proxy report and patient self-report of the QOL and HRQOL
      were 0.63 and 0.40, respectively. Correlations of QOL with pain and disease
      severity were moderately negative (r = -0.55 and -0.56, respectively, p <
      0.0001). Correlations of HRQOL with pain and disease severity were strongly
      negative (r = -0.66 and r = -0.68, respectively, p < 0.0001). The MCID for
      improvement on the QOL was 7 mm, and for the HRQOL 11 mm. The MCID for
      deterioration in QOL was -33 mm, and for HRQOL -38 mm. CONCLUSION: The QoML
      questionnaire demonstrated fair parent-child agreement and good convergent
      construct validity. MCID scores will enable clinicians to interpret QoML
      questionnaire results in a clinically meaningful way.

PMID- 17183615
TI  - Canadian multidisciplinary core curriculum for musculoskeletal health.
AB  - OBJECTIVE: To determine the level of agreement among the Bone and Joint Decade
      Undergraduate Curriculum Group (BJDUCG) core curriculum recommendations for
      musculoskeletal (MSK) conditions targeted for undergraduate medical education and
      what the physicians and surgeons of Canada thought to be important at the
      postgraduate level of education. METHODS: An 80-item questionnaire was developed.
      A cross-sectional survey of educators representing 77 Canadian accredited
      academic programs representing 6 disciplines in medicine that manage patients
      with MSK conditions was completed. Histograms, Kruskal-Wallis, and principal
      component analyses were computed. RESULTS: In total, 164/175 (94%) respondents
      participated in the study. All 80 curriculum items received a mean score of at
      least 3.0/4.0. Sixty-four out of 80 items were ranked to be at least 3.5/4.0, and
      35 items were ranked to be at least 3.8/4.0, suggesting that these items may be
      core content for all disciplines. CONCLUSION: The World Health Organization
      declared the years 2000 to 2010 as The Bone and Joint Decade. The main goal is to
      improve the quality of life for people with MSK disorders worldwide. One aim of
      the BJD is to increase education of healthcare providers at all levels. The
      BJDUCG established a set of core curriculum recommendations for MSK conditions.
      Our study gives reliable statistical evidence of agreement among what the BJDUCG
      recommended for an MSK core curriculum for medical schools and what the
      physicians and surgeons of Canada thought to be important for residency education
      in several disciplines.

PMID- 17183616
TI  - Descriptive epidemiology of osteoarthritis in British Columbia, Canada.
AB  - OBJECTIVE: Osteoarthritis (OA) is a highly prevalent and often disabling disease.
      Data on the incidence of OA in the general population are limited. Our objectives
      were (1) to estimate OA prevalence and incidence rates by age and sex in a
      geographically defined population of 4 million people [British Columbia (BC),
      Canada] using an administrative database; and (2) to determine the effects of
      different administrative definitions of OA and observation (run-in) time on such
      estimates. METHODS: We used data on all visits to health professionals and
      hospital admissions covered by the Medical Services Plan (MSP) of BC for the
      fiscal years 1991-92 through 2000-01. OA was defined based on International
      Classification of Diseases, 9th Revision, diagnostic codes required for
      administrative purposes. RESULTS: The overall prevalence of OA in 2001 was 10.8%:
      8.9% in men and 12.6% in women. Prevalence was higher in women in all age groups.
      By age 70-74 years, about one-third of men and 40% of women had OA. Incidence
      rates in 2000-01 were 11.7 per 1000 person-years in the total population, 10.0 in
      men and 13.4 in women. Rates increased linearly with age between 50 and 80 years.
      Both prevalence and incidence depended strongly on the definition of OA and the
      run-in period. CONCLUSION: Prevalence of physician-diagnosed OA in BC was
      slightly lower than self-reported prevalence of arthritis in population surveys.
      Routinely collected administrative data could be a valuable source of information
      for OA surveillance, but more research is needed on the validity of OA diagnosis
      in administrative databases.

PMID- 17183617
TI  - Anti-thyroid autoantibody-associated interface dermatitis in individuals with
      undifferentiated connective tissue disease--an unrecognized subset of autoimmune
      disease?
AB  - OBJECTIVE: Skin conditions in individuals with undifferentiated connective tissue
      disease (UCTD) are poorly classified and characterized, and autoantibodies in
      serum can be heterogeneous and not always specific. We have identified a new
      subset of individuals with UCTD, interface dermatitis, and increased anti-thyroid
      antibodies. METHODS: We retrospectively reviewed 892 cases of individuals with
      UCTD. Serologic markers for CTD and autoantibodies against microsomes and/or
      thyroglobulin were analyzed. Skin lesions and medication history were documented,
      and persistent or recurrent skin lesions were biopsied. RESULTS: Anti-thyroid
      antibodies for thyroglobulin and/or microsomes (ATAb) were positive in 526 (59%).
      The ATAb(+) and ATAb(-) groups had similar antinuclear antibody (ANA) positivity
      (32% vs 28%, respectively), average age (59 vs 58 yrs), and female-male ratio
      (8:1 vs 6:1). ATAb positivity was significantly associated with a dermatitis
      manifested as erythematous macules/patches or papules on legs, upper arms, back,
      and shoulders in 9% (47/526) of ATAb(+) individuals versus 2% (7/366) in ATAb(-)
      individuals (p < 0.0001). Seventeen individuals with dermatitis, 15 ATAb(+) and 2
      ATAb(-), had biopsies. Twelve biopsies (80%) from ATAb(+) individuals and one
      ATAb(-) individual showed a cell-poor lymphocytic interface dermatitis with
      vaculopathy of basal layer keratinocytes, dermal mucin deposition, and
      perivascular mononuclear inflammatory cell infiltrates in the upper dermis that
      spared eccrine glands. The interface dermatitis was not significantly associated
      with hypo- or hyperthyroidism, or medications. CONCLUSION: We describe an ATAb
      associated interface dermatitis in roughly 9% of ATAb(+) patients with UCTD,
      which may represent a new subset of autoimmune disease. ATAb may be a useful
      marker for some individuals with UCTD.

PMID- 17183618
TI  - Toll-like receptor-2 expression is upregulated in antigen-presenting cells from
      patients with psoriatic arthritis: a pathogenic role for innate immunity?
AB  - OBJECTIVE: To study Toll-like receptor-2 (TLR-2) and TLR-4 expression in antigen
      presenting cells from patients with psoriatic arthritis (PsA). METHODS: We
      measured expression of TLR-2 and TLR-4 in monocyte-derived dendritic cells from
      patients with PsA and with rheumatoid arthritis (RA), and in healthy controls.
      Dendritic cells were obtained from freshly isolated monocytes, stimulated with
      granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL
      4) after 6 days in culture. To obtain mature dendritic cells, lipopolysaccharide
      stimulation and 2 additional days in culture were necessary. The expression of
      TLR-2, TLR-4, HLA-DR, and CD86 was studied at baseline, at 6 days, and at 8 days
      by flow cytometry. To establish the functional properties of TLR expression we
      studied the following cytokines in cell supernatants: tumor necrosis factor-alpha
      (TNF-alpha), interferon-gamma (IFN-gamma), IL-2, IL-4, IL-5, IL-10, IL-12, IL-13,
      and GM-CSF. TLR-2 expression was confirmed by Western blot analysis. RESULTS: Ten
      PsA patients with active disease and 8 healthy controls were studied, along with
      4 patients with RA. TLR-2 expression was increased in immature dendritic cells
      from patients with PsA. Monocytes and mature dendritic cells did not show
      statistically significant differences. No difference was observed in the
      expression of TLR-4 in any cell type. The supernatant expression of cytokines
      showed a Th1 pattern, mostly with increased expression of TNF-alpha, IFN-gamma,
      and IL-2. Western blot analysis confirmed the increased expression of TLR-2.
      CONCLUSION: Upregulation of TLR-2 expression provides support for a role of the
      innate immune system in the pathogenesis of PsA.

PMID- 17183619
TI  - Renal biopsy in lupus patients with low levels of proteinuria.
AB  - OBJECTIVE: Early and accurate detection of kidney involvement in systemic lupus
      erythematosus (SLE) improves outcomes. Renal biopsy is required for definitive
      diagnosis of lupus nephritis (LN). In the absence of acute renal failure (ARF),
      moderate levels of proteinuria (> 1000 mg/24 h) have been recommended by some to
      justify biopsy. We investigated whether patients with lower levels of proteinuria
      without ARF have significant renal disease and should be routinely biopsied.
      METHODS: We retrospectively evaluated 21 SLE patients with 24-h urine protein <
      1000 mg who underwent kidney biopsies. Indications for biopsy included new-onset
      proteinuria, increasing proteinuria, or hematuria (> 5 red blood cells per high
      power field). No patient had ARF. RESULTS: Sixteen of 21 (77%) biopsies were
      diagnostic of LN: 3 class II, 10 class III (5 superimposed class V), 2 class IV
      (one superimposed class V), and one with class V. One patient had thrombotic
      microangiopathy. The remaining 4 (23%) patients had non-lupus renal disease.
      Thirteen patients with class III or greater LN required alterations in
      therapeutic regimen because of biopsy findings. Of 7 patients without hematuria
      at the time of biopsy, 4 (57%) had class III, IV, or V LN. One patient without
      hematuria and < 500 mg/24 h proteinuria had class III LN. CONCLUSION: We found
      significant renal involvement (Class III, IV, or V LN) in SLE patients with <
      1000 mg proteinuria with or without hematuria. Our findings suggest that biopsy
      be strongly considered in this patient population.

PMID- 17183620
TI  - Summarizing disease features over time: II. Variability measures of SLEDAI-2K.
AB  - OBJECTIVE: o determine if the variability of the Systemic Lupus Erythematosus
      Disease Activity Index 2000 (SLEDAI-2K), along with the Adjusted Mean SLEDAI-2K
      (AMS), can better predict major outcomes in SLE than the AMS alone. METHODS:
      Patients were followed in the Lupus Clinic at 2-6 month intervals. Clinical and
      laboratory information necessary to compute the SLEDAI-2K and Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology damage index
      was collected prospectively and entered onto a computerized database. Patients
      followed for a minimum of 3 visits, and without absence for a period > 18
      consecutive months, were included in the study. Six different approaches to
      measure variability of SLEDAI-2K were evaluated for each visit, along with AMS.
      Approaches were the standard deviation, the slope, average rate of change by
      visit, the range, the coefficient of variation, and the Percentage of the visits
      with a change in SLEDAI-2K > or = 3. The SLE outcomes under study were death,
      presence of damage, coronary artery disease (CAD), and osteonecrosis (ON). The
      predictability of each outcome was evaluated through time-dependent covariate
      survival analyses. Regression models included other known major risk factors such
      as sex, age at diagnosis, SLEDAI-2K at presentation, and disease duration.
      RESULTS: Five hundred seventy-five patients seen from 1970 to 2002 were included.
      The average time between visits was 4.0 +/- 2.2 months. Eighty-five patients
      died, 325 developed damage, 55 had CAD, and 68 had ON. None of the 6 variability
      measures added more statistical significance in the prediction of any of the 4
      outcomes. For the prediction of survival, AMS [hazard ratio (HR) = 1.16, p <
      0.0001] and age at diagnosis (HR 1.05, p < 0.0001) were the only significant risk
      factors. For presence of damage, AMS (HR 1.06, p < 0.0001), age at diagnosis (HR
      1.02, p = 0.0004), and disease duration (HR 1.05, p < 0.0001) were predictors.
      CAD was predicted by AMS (HR 1.12, p = 0.0003), male sex (HR 2.31, p = 0.02), age
      at diagnosis (HR 1.06, p < 0.0001), and disease duration (HR 1.10, p < 0.0001).
      For ON, SLEDAI-2K at presentation (HR 1.04, p = 0.003) and disease duration (HR
      0.92, p = 0.05) were significant risk factors. CONCLUSION: Multivariate analysis
      revealed that AMS, independent of variability of the SLEDAI-2K, is an important
      predictor of major outcomes in SLE.

PMID- 17183621
TI  - The economic burden of rheumatoid arthritis in a developing nation: results from
      a one-year prospective cohort study in Thailand.
AB  - OBJECTIVE: To assess annual direct and indirect costs in a prospective cohort of
      patients with rheumatoid arthritis (RA) in Thailand from the societal
      perspective. METHODS: Data on costs and intangible losses were prospectively
      collected at regular intervals over a one-year period from 158 RA patients who
      attended a major tertiary care facility in Bangkok, Thailand. Direct medical,
      direct nonmedical, indirect, and total costs were estimated according to
      patients' respective health insurance conditions and converted to 2001 US dollars
      using published purchasing power parity estimates. Sensitivity analyses were
      performed and the predictors of costs and intangible losses were investigated.
      RESULTS: The average societal cost of RA was estimated to be 2682 US dollars,
      41.4% of patients' average annual income. Average direct and indirect costs were
      estimated to amount to 2135 US dollars and 547 US dollars per patient per year,
      respectively. Seventy-three patients (46.2%) experienced at least one event of
      intangible losses and 46 patients (29.1%) had decreased earnings ability because
      of RA. Poor physical function, joint deformity, high number of disease modifying
      antirheumatic drugs, and steroid use contributed to higher costs and presence of
      intangible losses. CONCLUSION: RA consumes a significant proportion of patients'
      annual average incomes and poses a significant economic burden to society. Since
      RA mainly affects a working-age population, early and timely treatment of this
      disease can improve both the suffering and the economic productivity of patients
      in Thailand.

PMID- 17183622
TI  - Prevalent rheumatoid arthritis and diabetes among NHANES III participants aged 60
      and older.
AB  - OBJECTIVE: This study examines the cross-sectional association between prevalent
      rheumatoid arthritis (RA) and diabetes among noninstitutionalized US civilians
      aged >or= 60 years between 1988 and 1994. METHODS: Using National Health and
      Nutrition Examination Survey III data from the National Center for Health
      Statistics, RA and diabetes were identified using several classification schemes.
      In total, 5302 survey participants aged >or= 60 years were included in logistic
      regression analyses taking survey weights into account. We also conducted
      sensitivity analyses restricting the study population to participants not
      recently prescribed glucocorticoids and fasting at least 8 hours prior to blood
      draw, as well as data incorporated from the Multiple Imputation Project. RESULTS:
      Among the 5302 participants aged >or= 60, 144 participants had RA and 24 of these
      also were found to have prevalent diabetes. The adjusted odds ratios for the
      cross-sectional association between RA and diabetes ranged from 1.1 to 1.5, but
      did not reach statistical significance. CONCLUSION: While this study cannot
      definitively rule out a modest non-null association, we can conclude that there
      is no evidence of a strong cross-sectional association between prevalent RA and
      diabetes in subjects aged >or= 60 years. Future longitudinal studies with more
      participants with RA are required to further evaluate a possible association
      between RA and the incidence of diabetes.

PMID- 17183623
TI  - Sustained remission and reduced radiographic progression with combination disease
      modifying antirheumatic drugs in early rheumatoid arthritis.
AB  - OBJECTIVE: To study sustainability of remission and good treatment response, and
      the association of both with radiographic progression, in early rheumatoid
      arthritis (RA) in the Finnish Rheumatoid Arthritis Combination Therapy trial (FIN
      RACo). METHODS: Patients were randomized to receive either a combination of
      disease modifying antirheumatic drugs (DMARD; COMBI, n = 97) or a single DMARD
      (SINGLE, n = 98). Remission was defined according to modified American College of
      Rheumatology (ACR) remission criteria and Disease Activity Score 28 joint count
      (DAS28) < or = 2.6, and sustained remission as presence of remission at 6, 12,
      and 24 months. Good treatment response was defined as DAS28 (3/4) 3.2 and
      decrease of DAS28 >1.2. RESULTS: In 169 patients with complete data, 33 (42%)
      COMBI and 18 (20%) SINGLE patients achieved modified ACR remission at 2 years,
      which was sustained in 11 (14%) COMBI and 3 (3%) SINGLE patients. Fifty-four
      (68%) COMBI and 37 (41%) SINGLE patients were in DAS28 remission at 2 years,
      which was sustained in 40 (51%) COMBI and 14 (16%) SINGLE patients. Good
      treatment response was sustained in 67% of COMBI and 27% of SINGLE patients. Over
      2 years, the Larsen score increased by a median of 1 (95% CI 0-2) in patients in
      sustained DAS28 remission compared to 4 (95% CI 2-16) in patients who were in
      DAS28 remission at 6 months but lost it later; and by 6 (95% CI 2-10) in patients
      who were not in remission at 6 months. CONCLUSION: A remarkable proportion of
      patients with early RA treated with combinations of DMARD were in remission at 2
      years, and remission was more often sustained compared to patients treated with a
      single DMARD. Sustained remission protects against radiographic joint damage.

PMID- 17183624
TI  - Use of ethidium bromide monoazide for quantification of viable and dead mixed
      bacterial flora from fish fillets by polymerase chain reaction.
AB  - Ethidium bromide monoazide (EMA) was utilized to selectively allow conventional
      PCR amplification of target DNA from viable but not dead cells from a broth
      culture of bacterial mixed flora derived from cod fillets. The universal primers
      designated DG74 and RW01 that amplify a 370-bp sequence of a highly conserved
      region of all eubacterial 16S rDNA were used for the PCR. The use of 10 microg/ml
      or less of EMA did not inhibit the PCR amplification of DNA derived from viable
      bacteria. The minimum amount of EMA to completely inhibit the PCR amplification
      of DNA derived from dead bacterial cells was 0.8 microg/ml. Amplification of
      target DNA from only viable cells in a suspension with dead cells was selectively
      accomplished by first treating the cells with 1 microg/ml of EMA. A standard
      curve was generated relating the intensity of fluorescence of DNA bands to the
      log of CFU of mixed bacterial cultures for rapidly assessing the number of
      genomic targets per PCR derived from the number of CFU. A linear range of DNA
      amplification was exhibited from 1 x 10(2) to 1 x 10(5) genomic targets per PCR.
      The viable/dead cell discrimination with the EMA-PCR method was evaluated by
      comparison with plate counts following freezing and thawing. Thawing frozen cell
      suspensions initially containing 1 x 10(5) CFU/ml at 4, 20, and 37 degrees C
      yielded a 0.8 log reduction in the number of viable cells determined by both
      plate counts and EMA-PCR. In contrast, thawing for 5 min at 70 degrees C resulted
      in a 5 log reduction in CFU derived from plate counts (no CFU detected) whereas
      the EMA-PCR procedure resulted in only a 2.8 log reduction in genomic targets,
      possibly reflecting greater damage to enzymes or ribosomes at 70 degrees C to a
      minority of the mixed population compared to membrane damage.

PMID- 17183625
TI  - Radical cystectomy--often too late? 1987.

PMID- 17183626
TI  - Lipid profile good for new agent.

PMID- 17183627
TI  - The Mainz pouch (mixed augmentation ileum 'n zecum) for bladder augmentation and
      continent urinary diversion. 1985.

PMID- 17183628
TI  - Changes in the slope of the CD4 cell count increase after initiation of potent
      antiretroviral treatment.
AB  - SUMMARY: Two phases of CD4+ T-cell increases are seen soon after potent
      antiretroviral therapy (ART) is initiated. In this 72-week analysis of 101
      subjects with sustained viral suppression, we estimate the inflection point
      between the 2 phases to be 10 weeks after treatment initiation. Higher
      pretreatment HIV-1 RNA levels were associated with steeper initial CD4+ T-cell
      increases, likely reflecting greater redistribution of cells from lymphoid tissue
      to the peripheral blood compartment.

PMID- 17183629
TI  - Emended classification of xanthomonad pathogens on citrus.

PMID- 17183630
TI  - [Reply to the authors. Infectious complications in lung transplantation for
      cystic fibrosis].

PMID- 17183631
TI  - Neural substrate of cold-seeking behavior in endotoxin shock.
AB  - Systemic inflammation is a leading cause of hospital death. Mild systemic
      inflammation is accompanied by warmth-seeking behavior (and fever), whereas
      severe inflammation is associated with cold-seeking behavior (and hypothermia).
      Both behaviors are adaptive. Which brain structures mediate which behavior is
      unknown. The involvement of hypothalamic structures, namely, the preoptic area
      (POA), paraventricular nucleus (PVH), or dorsomedial nucleus (DMH), in
      thermoregulatory behaviors associated with endotoxin (lipopolysaccharide [LPS])
      induced systemic inflammation was studied in rats. The rats were allowed to
      select their thermal environment by freely moving in a thermogradient apparatus.
      A low intravenous dose of Escherichia coli LPS (10 microg/kg) caused warmth
      seeking behavior, whereas a high, shock-inducing dose (5,000 microg/kg) caused
      cold-seeking behavior. Bilateral electrocoagulation of the PVH or DMH, but not of
      the POA, prevented this cold-seeking response. Lesioning the DMH with ibotenic
      acid, an excitotoxin that destroys neuronal bodies but spares fibers of passage,
      also prevented LPS-induced cold-seeking behavior; lesioning the PVH with
      ibotenate did not affect it. Lesion of no structure affected cold-seeking
      behavior induced by heat exposure or by pharmacological stimulation of the
      transient receptor potential (TRP) vanilloid-1 channel ("warmth receptor"). Nor
      did any lesion affect warmth-seeking behavior induced by a low dose of LPS, cold
      exposure, or pharmacological stimulation of the TRP melastatin-8 ("cold
      receptor"). We conclude that LPS-induced cold-seeking response is mediated by
      neuronal bodies located in the DMH and neural fibers passing through the PVH.
      These are the first two landmarks on the map of the circuitry of cold-seeking
      behavior associated with endotoxin shock.

PMID- 17183632
TI  - Differences between Belgian and Brazilian group A Streptococcus epidemiologic
      landscape.
AB  - BACKGROUND: Group A Streptococcus (GAS) clinical and molecular epidemiology
      varies with location and time. These differences are not or are poorly
      understood. METHODS AND FINDINGS: We prospectively studied the epidemiology of
      GAS infections among children in outpatient hospital clinics in Brussels
      (Belgium) and Brasilia (Brazil). Clinical questionnaires were filled out and
      microbiological sampling was performed. GAS isolates were emm-typed according to
      the Center for Disease Control protocol. emm pattern was predicted for each
      isolate. 334 GAS isolates were recovered from 706 children. Skin infections were
      frequent in Brasilia (48% of the GAS infections), whereas pharyngitis were
      predominant (88%) in Brussels. The mean age of children with GAS pharyngitis in
      Brussels was lower than in Brasilia (65/92 months, p<0.001). emm-typing revealed
      striking differences between Brazilian and Belgian GAS isolates. While 20
      distinct emm-types were identified among 200 Belgian isolates, 48 were found
      among 128 Brazilian isolates. Belgian isolates belong mainly to emm pattern A-C
      (55%) and E (42.5%) while emm pattern E (51.5%) and D (36%) were predominant in
      Brasilia. In Brasilia, emm pattern D isolates were recovered from 18.5% of the
      pharyngitis, although this emm pattern is supposed to have a skin tropism. By
      contrast, A-C pattern isolates were infrequently recovered in a region where
      rheumatic fever is still highly prevalent. CONCLUSIONS: Epidemiologic features of
      GAS from a pediatric population were very different in an industrialised country
      and a low incomes region, not only in term of clinical presentation, but also in
      terms of genetic diversity and distribution of emm patterns. These differences
      should be taken into account for designing treatment guidelines and vaccine
      strategies.

PMID- 17183633
TI  - Factors affecting frequency discrimination of vibrotactile stimuli: implications
      for cortical encoding.
AB  - BACKGROUND: Measuring perceptual judgments about stimuli while manipulating their
      physical characteristics can uncover the neural algorithms underlying sensory
      processing. We carried out psychophysical experiments to examine how humans
      discriminate vibrotactile stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Subjects
      compared the frequencies of two sinusoidal vibrations applied sequentially to one
      fingertip. Performance was reduced when (1) the root mean square velocity (or
      energy) of the vibrations was equated by adjusting their amplitudes, and (2) the
      vibrations were noisy (their temporal structure was irregular). These effects
      were super-additive when subjects compared noisy vibrations that had equal
      velocity, indicating that frequency judgments became more dependent on the
      vibrations' temporal structure when differential information about velocity was
      eliminated. To investigate which areas of the somatosensory system use
      information about velocity and temporal structure, we required subjects to
      compare vibrations applied sequentially to opposite hands. This paradigm exploits
      the fact that tactile input to neurons at early levels (e.g., the primary
      somatosensory cortex, SI) is largely confined to the contralateral side of the
      body, so these neurons are less able to contribute to vibration comparisons
      between hands. The subjects' performance was still sensitive to differences in
      vibration velocity, but became less sensitive to noise. CONCLUSIONS/SIGNIFICANCE:
      We conclude that vibration frequency is represented in different ways by
      different mechanisms distributed across multiple cortical regions. Which
      mechanisms support the "readout" of frequency varies according to the information
      present in the vibration. Overall, the present findings are consistent with a
      model in which information about vibration velocity is coded in regions beyond
      SI. While adaptive processes within SI also contribute to the representation of
      frequency, this adaptation is influenced by the temporal regularity of the
      vibration.

PMID- 17183634
TI  - Vaccinia scars associated with improved survival among adults in rural Guinea
      Bissau.
AB  - BACKGROUND: In urban Guinea-Bissau, adults with a vaccinia scar had better
      survival but also a higher prevalence of HIV-2 infection. We therefore
      investigated the association between vaccinia scar and survival and HIV infection
      in a rural area of Guinea-Bissau. METHODOLOGY/PRINCIPAL FINDINGS: In connection
      with a study of HIV in rural Guinea-Bissau, we assessed vaccinia and BCG scars in
      193 HIV-1 or HIV-2 infected and 174 uninfected participants. Mortality was
      assessed after 2(1/2)-3 years of follow-up. The analyses were adjusted for age,
      sex, village, and HIV status. The prevalence of vaccinia scar was associated with
      age, village, and HIV-2 status but not with sex and schooling. Compared with
      individuals without any scar, individuals with a vaccinia scar had better
      survival (mortality rate ratio (MR) = 0.22 (95% CI 0.08-0.61)), the MR being 0.19
      (95% CI 0.06-0.57) for women and 0.40 (95% CI 0.04-3.74) for men. Estimates were
      similar for HIV-2 infected and HIV-1 and HIV-2 uninfected individuals. The HIV-2
      prevalence was higher among individuals with a vaccinia scar compared to
      individuals without a vaccinia scar (RR = 1.57 (95% CI 1.02-2.36)). CONCLUSION:
      The present study supports the hypothesis that vaccinia vaccination may have a
      non-specific beneficial effect on adult survival.

PMID- 17183635
TI  - Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and
      neonates revealed after regulatory T cell removal.
AB  - BACKGROUND: In utero transmission of HIV-1 occurs on average in only 3%-15% of
      HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus,
      despite potential exposure, the majority of infants remain uninfected. Weak HIV-1
      specific T-cell responses have been detected in children exposed to HIV-1, and
      potentially contribute to protection against infection. We, and others, have
      recently shown that the removal of CD4(+) CD25(+) T-regulatory (Treg) cells can
      reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults.
      Here, we hypothesized that Treg cells could suppress HIV-1-specific immune
      responses in young children. METHODOLOGY/PRINCIPAL FINDINGS: We studied two
      cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as
      well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and
      HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation,
      and cell-mediated immune responses. We detected high levels of CD4(+) CD25(+)
      CD127(-) Treg cells and low levels of CD4(+) and CD8(+) T cell activation in the
      cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses
      in all of the children exposed to the virus. These T-cell responses were not seen
      in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of
      CD4(+) CD25(+) Treg cells from the cord blood of EU newborns strikingly augmented
      both CD4(+) and CD8(+) HIV-1-specific immune responses. CONCLUSIONS/SIGNIFICANCE:
      This study provides new evidence that EU infants can mount strong HIV-1-specific
      T cell responses, and that in utero CD4(+) CD25(+) T-regulatory cells may be
      contributing to the lack of vertical transmission by reducing T cell activation.

PMID- 17183636
TI  - Policy adjustment in a dynamic economic game.
AB  - Making sequential decisions to harvest rewards is a notoriously difficult
      problem. One difficulty is that the real world is not stationary and the reward
      expected from a contemplated action may depend in complex ways on the history of
      an animal's choices. Previous functional neuroimaging work combined with
      principled models has detected brain responses that correlate with computations
      thought to guide simple learning and action choice. Those works generally
      employed instrumental conditioning tasks with fixed action-reward contingencies.
      For real-world learning problems, the history of reward-harvesting choices can
      change the likelihood of rewards collected by the same choices in the near-term
      future. We used functional MRI to probe brain and behavioral responses in a
      continuous decision-making task where reward contingency is a function of both a
      subject's immediate choice and his choice history. In these more complex tasks,
      we demonstrated that a simple actor-critic model can account for both the
      subjects' behavioral and brain responses, and identified a reward prediction
      error signal in ventral striatal structures active during these non-stationary
      decision tasks. However, a sudden introduction of new reward structures engages
      more complex control circuitry in the prefrontal cortex (inferior frontal gyrus
      and anterior insula) and is not captured by a simple actor-critic model. Taken
      together, these results extend our knowledge of reward-learning signals into more
      complex, history-dependent choice tasks. They also highlight the important
      interplay between striatum and prefrontal cortex as decision-makers respond to
      the strategic demands imposed by non-stationary reward environments more
      reminiscent of real-world tasks.

PMID- 17183637
TI  - A comparative study on the cost of new antibiotics and drugs of other therapeutic
      categories.
AB  - BACKGROUND: Drug treatment is becoming more expensive due to the increased cost
      for the introduction of new drugs, and there seems to be an uneven distribution
      of medication cost for different therapeutic categories. We hypothesized that the
      cost of new antimicrobial agents may differ from that of other therapeutic
      categories and this may play a role in the stagnation of development of new
      antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pharmaco-economical
      comparative analysis of the drug cost of treatment for new agents introduced in
      the United States drug market in various therapeutic categories. We calculated
      the drug cost (in US dollars) of a ten-day treatment of all new drugs approved by
      the FDA during the period between January 1997 and July 2003, according to the
      2004 Red Book Pharmacy's Fundamental Reference. New anti-neoplastic agents were
      found to be the most expensive drugs in comparison to all other therapeutic
      categories, with a median ten-day drug-treatment cost of US$848 compared to the
      median ten-day drug-treatment costs of all other categories ranging from US$29 to
      US$301. On the other hand, new antimicrobial drugs were found to be much less
      expensive, with a median ten-day drug-treatment cost of US$137 and $US85 for all
      anti-microbial agents and for anti-microbial agents excluding anti-HIV
      medications, respectively. CONCLUSIONS/SIGNIFICANCE: The drug-treatment cost of
      new medications varies considerably by different therapeutic categories. This
      fact may influence industry decisions regarding the development of new drugs and
      may play a role in the shortage of new antimicrobial agents in the fight against
      the serious problem of antimicrobial resistance.

PMID- 17183638
TI  - The effectiveness of contact tracing in emerging epidemics.
AB  - BACKGROUND: Contact tracing plays an important role in the control of emerging
      infectious diseases, but little is known yet about its effectiveness. Here we
      deduce from a generic mathematical model how effectiveness of tracing relates to
      various aspects of time, such as the course of individual infectivity, the
      (variability in) time between infection and symptom-based detection, and delays
      in the tracing process. In addition, the possibility of iteratively tracing of
      yet asymptomatic infecteds is considered. With these insights we explain why
      contact tracing was and will be effective for control of smallpox and SARS, only
      partially effective for foot-and-mouth disease, and likely not effective for
      influenza. METHODS AND FINDINGS: We investigate contact tracing in a model of an
      emerging epidemic that is flexible enough to use for most infections. We consider
      isolation of symptomatic infecteds as the basic scenario, and express
      effectiveness as the proportion of contacts that need to be traced for a
      reproduction ratio smaller than 1. We obtain general results for special cases,
      which are interpreted with respect to the likely success of tracing for
      influenza, smallpox, SARS, and foot-and-mouth disease epidemics. CONCLUSIONS: We
      conclude that (1) there is no general predictive formula for the proportion to be
      traced as there is for the proportion to be vaccinated; (2) variability in time
      to detection is favourable for effective tracing; (3) tracing effectiveness need
      not be sensitive to the duration of the latent period and tracing delays; (4)
      iterative tracing primarily improves effectiveness when single-step tracing is on
      the brink of being effective.

PMID- 17183639
TI  - Short and long-term effects of hVEGF-A(165) in Cre-activated transgenic mice.
AB  - We have generated a transgenic mouse where hVEGF-A(165) expression has been
      silenced with loxP-STOP fragment, and we used this model to study the effects of
      hVEGF-A(165) over-expression in mice after systemic adenovirus mediated Cre-gene
      transfer. Unlike previous conventional transgenic models, this model leads to the
      expression of hVEGF-A(165) in only a low number of cells in the target tissues in
      adult mice. Levels of hVEGF-A(165) expression were moderate and morphological
      changes were found mainly in the liver, showing typical signs of active
      angiogenesis. Most mice were healthy without any major consequences up to 18
      months after the activation of hVEGF-A(165) expression. However, one mouse with a
      high plasma hVEGF-A(165) level died spontaneously because of bleeding into
      abdominal cavity and having liver hemangioma, haemorrhagic paratubarian cystic
      lesions and spleen peliosis. Also, two mice developed malignant tumors
      (hepatocellular carcinoma and lung adenocarcinoma), which were not seen in
      control mice. We conclude that long-term uncontrolled hVEGF-A(165) expression in
      only a limited number of target cells in adult mice can be associated with
      pathological changes, including possible formation of malignant tumors and
      uncontrolled bleeding in target tissues. These findings have implications for the
      design of long-term clinical trials using hVEGF-A(165) gene and protein.

PMID- 17183640
TI  - Cognitive aging in zebrafish.
AB  - BACKGROUND: Age-related impairments in cognitive functions represent a growing
      clinical and social issue. Genetic and behavioral characterization of animal
      models can provide critical information on the intrinsic and environmental
      factors that determine the deterioration or preservation of cognitive abilities
      throughout life. METHODOLOGY/PRINCIPAL FINDINGS: Behavior of wild-type, mutant
      and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis
      technique. Conditioned responses to spatial, visual and temporal cues were
      investigated in young, middle-aged and old animals. The results demonstrate that
      zebrafish aging is associated with changes in cognitive responses to emotionally
      positive and negative experiences, reduced generalization of adaptive
      associations, increased stereotypic and reduced exploratory behavior and altered
      temporal entrainment. Genetic upregulation of cholinergic transmission attenuates
      cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type
      siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the
      onset of cognitive impairment in young zebrafish. CONCLUSIONS/SIGNIFICANCE: These
      findings would allow the use of powerful molecular biological resources
      accumulated in the zebrafish field to address the mechanisms of cognitive
      senescence, and promote the search for therapeutic strategies which may attenuate
      age-related cognitive decline.

PMID- 17183641
TI  - E-cadherin-coated plates maintain pluripotent ES cells without colony formation.
AB  - Embryonic stem (ES) cells cultured on gelatin-coated plates or feeder layers form
      tight aggregated colonies by the E-cadherin-mediated cell-cell adhesions. Here we
      show that murine ES cells do not make cell-cell contacts or form colonies when
      cultured on the plate coated with a fusion protein of E-cadherin and IgG Fc
      domain. The cells in culture retain all ES cell features including pluripotency
      to differentiate into cells of all three germ layers and germ-line transmission
      after extended culture. Furthermore, they show a higher proliferative ability,
      lower dependency on LIF, and higher transfection efficiency than colony-forming
      conditions. Our results suggest that aggregated colony formation might inhibit
      diffusion of soluble factors and increase cell-cell communication, which may
      result in a heterogeneous environment within and between surrounding cells of the
      colony. This method should enable more efficient and scalable culture of ES
      cells, an important step towards the clinical application of these cells.

PMID- 17183642
TI  - Requirement of TORC1 for late-phase long-term potentiation in the hippocampus.
AB  - Late-phase long-term potentiation (L-LTP) and long-term memory depend on the
      transcription of mRNA of CRE-driven genes and synthesis of proteins. However, how
      synaptic signals propagate to the nucleus is unclear. Here we report that the
      CREB coactivator TORC1 (transducer of regulated CREB activity 1) undergoes
      neuronal activity-induced translocation from the cytoplasm to the nucleus, a
      process required for CRE-dependent gene expression and L-LTP. Overexpressing a
      dominant-negative form of TORC1 or down-regulating TORC1 expression prevented
      activity-dependent transcription of CREB target genes in cultured hippocampal
      neurons, while overexpressing a wild-type form of TORC1 facilitated basal and
      activity-induced transcription of CREB target genes. Furthermore, overexpressing
      the dominant-negative form of TORC1 suppressed the maintenance of L-LTP without
      affecting early-phase LTP, while overexpressing the wild-type form of TORC1
      facilitated the induction of L-LTP in hippocampal slices. Our results indicate
      that TORC1 is essential for CRE-driven gene expression and maintenance of long
      term synaptic potentiation.

PMID- 17183643
TI  - Multilocus sequence typing breathes life into a microbial metagenome.
AB  - Shot-gun sequencing of DNA isolated from the environment and the assembly of
      metagenomes from the resulting data has considerably advanced the study of
      microbial diversity. However, the subsequent matching of these hypothetical
      metagenomes to cultivable microorganisms is a limitation of such cultivation
      independent methods of population analysis. Using a nucleotide sequence-based
      genetic typing method, multilocus sequence typing, we were able for the first
      time to match clonal cultivable isolates to a published and controversial
      bacterial metagenome, Burkholderia SAR-1, which derived from analysis of the
      Sargasso Sea. The matching cultivable isolates were all associated with infection
      and geographically widely distributed; taxonomic analysis demonstrated they were
      members of Burkholderia cepacia complex Group K. Comparison of the Burkholderia
      SAR-1 metagenome to closely related B. cepacia complex genomes indicated that it
      was greater than 98% intact in terms of conserved genes, and it also shared
      complete sequence identity with the cultivable isolates at random loci beyond the
      genes sampled by the multilocus sequence typing. Two features of the extant
      cultivable clones support the argument that the Burkholderia SAR-1 sequence may
      have been a contaminant in the original metagenomic survey: (i) their growth in
      conditions reflective of sea water was poor, suggesting the ocean was not their
      preferred habitat, and (ii) several of the matching isolates were
      epidemiologically linked to outbreaks of infection that resulted from
      contaminated medical devices or products, indicating an adaptive fitness of this
      bacterial strain towards contamination-associated environments. The ability to
      match identical cultivable strains of bacteria to a hypothetical metagenome is a
      unique feature of nucleotide sequence-based microbial typing methods; such
      matching would not have been possible with more traditional methods of genetic
      typing, such as those based on pattern matching of genomic restriction fragments
      or amplified DNA fragments. Overall, we have taken the first steps in moving the
      status of the Burkholderia SAR-1 metagenome from a hypothetical entity towards
      the basis for life of cultivable strains that may now be analysed in conjunction
      with the assembled metagenomic sequence data by the wider scientific community.

PMID- 17183644
TI  - Molecular pathogenesis and therapy of polycythemia induced in mice by JAK2 V617F.
AB  - BACKGROUND: A somatic activating mutation (V617F) in the JAK2 tyrosine kinase was
      recently discovered in the majority of patients with polycythemia vera (PV), and
      some with essential thrombocythemia (ET) and chronic idiopathic myelofibrosis.
      However, the role of mutant JAK2 in disease pathogenesis is unclear. METHODS AND
      FINDINGS: We expressed murine JAK2 WT or V617F via retroviral bone marrow
      transduction/transplantation in the hematopoietic system of two different inbred
      mouse strains, Balb/c and C57Bl/6 (B6). In both strains, JAK2 V617F, but not JAK2
      WT, induced non-fatal polycythemia characterized by increased hematocrit and
      hemoglobin, reticulocytosis, splenomegaly, low plasma erythropoietin (Epo), and
      Epo-independent erythroid colonies. JAK2 V617F also induced leukocytosis and
      neutrophilia that was much more prominent in Balb/c mice than in B6. Platelet
      counts were not affected in either strain despite expression of JAK2 V617F in
      megakaryocytes and markedly prolonged tail bleeding times. The polycythemia
      tended to resolve after several months, coincident with increased spleen and
      marrow fibrosis, but was resurrected by transplantation to secondary recipients.
      Using donor mice with mutations in Lyn, Hck, and Fgr, we demonstrated that the
      polycythemia was independent of Src kinases. Polycythemia and reticulocytosis
      responded to treatment with imatinib or a JAK2 inhibitor, but were unresponsive
      to the Src inhibitor dasatinib. CONCLUSIONS: These findings demonstrate that JAK2
      V617F induces Epo-independent expansion of the erythroid lineage in vivo. The
      fact that the central erythroid features of PV are recapitulated by expression of
      JAK2 V617F argues that it is the primary and direct cause of human PV. The lack
      of thrombocytosis suggests that additional events may be required for JAK2 V617F
      to cause ET, but qualitative platelet abnormalities induced by JAK2 V617F may
      contribute to the hemostatic complications of PV. Despite the role of Src kinases
      in Epo signaling, our studies predict that Src inhibitors will be ineffective for
      therapy of PV. However, we provide proof-of-principle that a JAK2 inhibitor
      should have therapeutic effects on the polycythemia, and perhaps myelofibrosis
      and hemostatic abnormalities, suffered by MPD patients carrying the JAK2 V617F
      mutation.

PMID- 17183646
TI  - Allometric scaling of the active hematopoietic stem cell pool across mammals.
AB  - BACKGROUND: Many biological processes are characterized by allometric relations
      of the type Y = Y(0)M(b) between an observable Y and body mass M, which pervade
      at multiple levels of organization. In what regards the hematopoietic stem cell
      pool, there is experimental evidence that the size of the hematopoietic stem cell
      pool is conserved in mammals. However, demands for blood cell formation vary
      across mammals and thus the size of the active stem cell compartment could vary
      across species. METHODOLOGY/PRINCIPLE FINDINGS: Here we investigate the
      allometric scaling of the hematopoietic system in a large group of mammalian
      species using reticulocyte counts as a marker of the active stem cell pool. Our
      model predicts that the total number of active stem cells, in an adult mammal,
      scales with body mass with the exponent 3/4. CONCLUSION/SIGNIFICANCE: The scaling
      predicted here provides an intuitive justification of the Hayflick hypothesis and
      supports the current view of a small active stem cell pool supported by a large,
      quiescent reserve. The present scaling shows excellent agreement with the
      available (indirect) data for smaller mammals. The small size of the active stem
      cell pool enhances the role of stochastic effects in the overall dynamics of the
      hematopoietic system.

PMID- 17183645
TI  - Clues to neuro-degeneration in Niemann-Pick type C disease from global gene
      expression profiling.
AB  - BACKGROUND: Niemann-Pick Type C (NPC) disease is a neurodegenerative disease that
      is characterized by the accumulation of cholesterol and glycosphingolipids in the
      late endocytic pathway. The majority of NPC cases are due to mutations in the
      NPC1 gene. The precise function of this gene is not yet known.
      METHODOLOGY/PRINCIPAL FINDINGS: Using cDNA microarrays, we analyzed the genome
      wide expression patterns of human fibroblasts homozygous for the I1061T NPC1
      mutation that is characterized by a severe defect in the intracellular processing
      of low density lipoprotein-derived cholesterol. A distinct gene expression
      profile was identified in NPC fibroblasts from different individuals when
      compared with fibroblasts isolated from normal subjects. As expected, NPC1 mutant
      cells displayed an inappropriate homeostatic response to accumulated
      intracellular cholesterol. In addition, a number of striking parallels were
      observed between NPC disease and Alzheimer's disease. CONCLUSIONS/SIGNIFICANCE:
      Many genes involved in the trafficking and processing of amyloid precursor
      protein and the microtubule binding protein, tau, were more highly expressed.
      Numerous genes important for membrane traffic and the cellular regulation of
      calcium, metals and other ions were upregulated. Finally, NPC fibroblasts
      exhibited a gene expression profile indicative of oxidative stress. These changes
      are likely contributors to the pathophysiology of Niemann-Pick Type C disease.

PMID- 17183647
TI  - Societal learning in epidemics: intervention effectiveness during the 2003 SARS
      outbreak in Singapore.
AB  - BACKGROUND: Rapid response to outbreaks of emerging infectious diseases is
      impeded by uncertain diagnoses and delayed communication. Understanding the
      effect of inefficient response is a potentially important contribution of
      epidemic theory. To develop this understanding we studied societal learning
      during emerging outbreaks wherein patient removal accelerates as information is
      gathered and disseminated. METHODS AND FINDINGS: We developed an extension of a
      standard outbreak model, the simple stochastic epidemic, which accounts for
      societal learning. We obtained expressions for the expected outbreak size and the
      distribution of epidemic duration. We found that rapid learning noticeably
      affects the final outbreak size even when learning exhibits diminishing returns
      (relaxation). As an example, we estimated the learning rate for the 2003 outbreak
      of severe acute respiratory syndrome (SARS) in Singapore. Evidence for relaxation
      during the first eight weeks of the outbreak was inconclusive. We estimated that
      if societal learning had occurred at half the actual rate, the expected final
      size of the outbreak would have reached nearly 800 cases, more than three times
      the observed number of infections. By contrast, the expected outbreak size for
      societal learning twice as effective was 116 cases. CONCLUSION: These results
      show that the rate of societal learning can greatly affect the final size of
      disease outbreaks, justifying investment in early warning systems and
      attentiveness to disease outbreak by both government authorities and the public.
      We submit that the burden of emerging infections, including the risk of a global
      pandemic, could be efficiently reduced by improving procedures for rapid
      detection of outbreaks, alerting public health officials, and aggressively
      educating the public at the start of an outbreak.

PMID- 17183648
TI  - Isolation of non-tuberculous mycobacteria in children investigated for pulmonary
      tuberculosis.
AB  - OBJECTIVE: To evaluate the frequency and clinical significance of non-tuberculous
      mycobacteria (NTM) isolates among children investigated for pulmonary
      tuberculosis in a rural South African community. METHODS: Children were
      investigated for pulmonary tuberculosis as part of a tuberculosis vaccine
      surveillance program (2001-2005). The clinical features of children in whom NTM
      were isolated, from induced sputum or gastric lavage, were compared to those with
      culture-proven M. tuberculosis. RESULTS: Mycobacterial culture demonstrated 114
      NTM isolates from 109 of the 1,732 children investigated, a crude yield of 6%
      (95% CI 5-7). The comparative yield of positive NTM cultures from gastric lavage
      was 40% (95% CI 31-50), compared to 67% (95% CI 58-76) from induced sputum. 95%
      of children with NTM isolates were symptomatic. Two children were HIV-infected.
      By contrast, M. tuberculosis was isolated in 187 children, a crude yield of 11%
      (95% CI 9-12). Compared to those with culture-proven M. tuberculosis, children
      with NTM isolates were less likely to demonstrate acid-fast bacilli on direct
      smear microscopy (OR 0.19; 95% 0.0-0.76). Children with NTM were older
      (p<0.0001), and more likely to demonstrate constitutional symptoms (p = 0.001),
      including fever (p = 0.003) and loss of weight or failure to gain weight (p =
      0.04), but less likely to demonstrate a strongly positive tuberculin skin test
      (p<0.0001) or radiological features consistent with pulmonary tuberculosis (p =
      0.04). DISCUSSION: NTM were isolated in 6% of all children investigated for
      pulmonary tuberculosis and in more than one third of those with a positive
      mycobacterial culture. NTM may complicate the diagnosis of PTB in regions that
      lack capacity for mycobacterial species identification. The association of NTM
      isolates with constitutional symptoms suggestive of host recognition requires
      further investigation.

PMID- 17183649
TI  - Genetic influences on exercise participation in 37,051 twin pairs from seven
      countries.
AB  - BACKGROUND: A sedentary lifestyle remains a major threat to health in
      contemporary societies. To get more insight in the relative contribution of
      genetic and environmental influences on individual differences in exercise
      participation, twin samples from seven countries participating in the GenomEUtwin
      project were used. METHODOLOGY: Self-reported data on leisure time exercise
      behavior from Australia, Denmark, Finland, Norway, The Netherlands, Sweden and
      United Kingdom were used to create a comparable index of exercise participation
      in each country (60 minutes weekly at a minimum intensity of four metabolic
      equivalents). PRINCIPAL FINDINGS: Modest geographical variation in exercise
      participation was revealed in 85,198 subjects, aged 19-40 years. Modeling of
      monozygotic and dizygotic twin resemblance showed that genetic effects play an
      important role in explaining individual differences in exercise participation in
      each country. Shared environmental effects played no role except for Norwegian
      males. Heritability of exercise participation in males and females was similar
      and ranged from 48% to 71% (excluding Norwegian males). CONCLUSIONS: Genetic
      variation is important in individual exercise behavior and may involve genes
      influencing the acute mood effects of exercise, high exercise ability, high
      weight loss ability, and personality. This collaborative study suggests that
      attempts to find genes influencing exercise participation can pool exercise data
      across multiple countries and different instruments.

PMID- 17183650
TI  - Development of a tumor-selective approach to treat metastatic cancer.
AB  - BACKGROUND: Patients diagnosed with metastatic cancer have almost uniformly poor
      prognoses. The treatments available for patients with disseminated disease are
      usually not curative and have side effects that limit the therapy that can be
      given. A treatment that is selectively toxic to tumors would maximize the
      beneficial effects of therapy and minimize side effects, potentially enabling
      effective treatment to be administered. METHODS AND FINDINGS: We postulated that
      the tumor-tropic property of stem cells or progenitor cells could be exploited to
      selectively deliver a therapeutic gene to metastatic solid tumors, and that
      expression of an appropriate transgene at tumor loci might mediate cures of
      metastatic disease. To test this hypothesis, we injected HB1.F3.C1 cells
      transduced to express an enzyme that efficiently activates the anti-cancer
      prodrug CPT-11 intravenously into mice bearing disseminated neuroblastoma tumors.
      The HB1.F3.C1 cells migrated selectively to tumor sites regardless of the size or
      anatomical location of the tumors. Mice were then treated systemically with CPT
      11, and the efficacy of treatment was monitored. Mice treated with the
      combination of HB1.F3.C1 cells expressing the CPT-11-activating enzyme and this
      prodrug produced tumor-free survival of 100% of the mice for >6 months (P<0.001
      compared to control groups). CONCLUSIONS: The novel and significant finding of
      this study is that it may be possible to exploit the tumor-tropic property of
      stem or progenitor cells to mediate effective, tumor-selective therapy for
      metastatic tumors, for which no tolerated curative treatments are currently
      available.

PMID- 17183651
TI  - Long-term persistence of robust antibody and cytotoxic T cell responses in
      recovered patients infected with SARS coronavirus.
AB  - Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously
      recovered without clinical intervention. However, the immunological correlates
      associated with patients' recovery are currently unknown. In this report, we have
      sequentially monitored 30 recovered patients over a two-year period to
      characterize temporal changes in SARS-CoV-specific antibody responses as well as
      cytotoxic T cell (CTL) responses. We have found persistence of robust antibody
      and CTL responses in all of the study subjects throughout the study period, with
      a moderate decline one year after the onset of symptoms. We have also identified
      two potential major CTL epitopes in N proteins based on ELISPOT analysis of
      pooled peptides. However, despite the potent immune responses and clinical
      recovery, peripheral lymphocyte counts in the recovered patients have not yet
      been restored to normal levels. In summary, our study has, for the first time,
      characterized the temporal and dynamic changes of humoral and CTL responses in
      the natural history of SARS-recovered individuals, and strongly supports the
      notion that high and sustainable levels of immune responses correlate strongly
      with the disease outcome. Our findings have direct implications for future design
      and development of effective therapeutic agents and vaccines against SARS-CoV
      infection.

PMID- 17183652
TI  - The release of nitric oxide from S-nitrosothiols promotes angiogenesis.
AB  - BACKGROUND: Free nitric oxide (NO) reacts with sulphydryl residues to form S
      nitrosothiols, which act as NO reservoirs. We sought to determine whether thiol
      preserving agents and antioxidants, such as dithiothreitol (DTT) and vitamin C,
      induce NO release from S-nitrosylated proteins in endothelial cell cultures to
      promote angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: NO release was measured
      directly in cell supernatants using a Sievers NO Analyser, and in vitro
      angiogenesis was assessed by quantifying capillary-like tube network formation of
      porcine aortic endothelial cells (PAEC) on growth factor-reduced Matrigel.
      Incubation of PAEC with DTT or vitamin C significantly increased NO release in a
      concentration-dependent manner. However, the nitric oxide synthase (NOS)
      inhibitors, L-NNA and L-NIO, had no effect on DTT- or vitamin C-induced NO
      release, and there was no concomitant increase in the phosphorylation of
      endothelial NOS at serine-1177 following DTT or vitamin C treatment. DTT and
      vitamin C increased capillary-like tube network formation by nine- and two-fold,
      respectively, and the addition of copper ions doubled the effect of vitamin C.
      Surprisingly, DTT maintained endothelial tube networks for up to one month under
      serum-free conditions, and selective inhibitors of guanylyl cyclase (ODQ) and PKG
      (KT-5823) blocked this, demonstrating the requirement of cyclic GMP and PKG in
      this process. CONCLUSIONS/SIGNIFICANCE: Both DTT and vitamin C are capable of
      releasing sufficient NO from S-nitrosothiols to induce capillary morphogenesis.
      This study provides the first evidence that increased denitrosylation leads to
      increased bioavailability of NO, independent of NOS activity, to promote
      sustained angiogenesis.

PMID- 17183654
TI  - Spatial control of rabies on heterogeneous landscapes.
AB  - Rabies control in terrestrial wildlife reservoirs relies heavily on an oral
      rabies vaccine (ORV). In addition to direct ORV delivery to protect wildlife in
      natural habitats, vaccine corridors have been constructed to control the spread;
      these corridors are often developed around natural barriers, such as rivers, to
      enhance the effectiveness of vaccine deployment. However, the question of how to
      optimally deploy ORV around a river (or other natural barrier) to best exploit
      the barrier for rabies control has not been addressed using mathematical models.
      Given an advancing epidemic wave, should the vaccine be distributed on both sides
      of barrier, behind the barrier, or in front of it? Here, we introduce a new
      mathematical model for the dynamics of raccoon rabies on a spatially
      heterogeneous landscape that is both simple and realistic. We demonstrate that
      the vaccine should always be deployed behind a barrier to minimize the recurrence
      of subsequent epidemics. Although the oral rabies vaccine is sufficient to induce
      herd immunity inside the vaccinated area, it simultaneously creates a demographic
      refuge. When that refuge is in front of a natural barrier, seasonal dispersal
      from the vaccine corridor into an endemic region sustains epidemic oscillations
      of raccoon rabies. When the vaccine barrier creates a refuge behind the river,
      the low permeability of the barrier to host movement limits dispersal of the host
      population from the protected populations into the rabies endemic area and limits
      subsequent rabies epidemics.

PMID- 17183655
TI  - Perceptual learning of motion leads to faster flicker perception.
AB  - Critical flicker fusion thresholds (CFFT) describe when quick amplitude
      modulations of a light source become undetectable as the frequency of the
      modulation increases. The threshold at which CFF occurs has been shown to remain
      constant under repeated testing. Additionally, CFF thresholds are correlated with
      various measures of intelligence, and have been regarded by clinicians as a
      general measure of cortical processing capacity. For these reasons, CFF is used
      as a cognitive indicator in drug studies, as a measure of fatigue, and has been
      suggested as a diagnostic measure for various brain diseases. Here we report that
      CFFT increases dramatically in subjects who are trained with a motion-direction
      learning procedure. Control tasks demonstrate that CFFT changes are tightly
      coupled with improvements in discriminating the direction of motion stimuli, and
      are likely related to plasticity in low-level visual areas that are specialized
      to process motion signals. This plasticity is long-lasting and is retained for at
      least one year after training. Combined, these results show that CFFT relates to
      a specialized sensory process and bring into question that CFFT is a measure of
      high-level, or general, processes.

PMID- 17183653
TI  - Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression
      profiling.
AB  - POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an
      undifferentiated state. Here we show that global expression profiling of Oct3/4
      manipulated ES cells delineates the downstream target genes of Oct3/4. Combined
      with data from genome-wide chromatin-immunoprecipitation (ChIP) assays, this
      analysis identifies not only primary downstream targets of Oct3/4, but also
      secondary or tertiary targets. Furthermore, the analysis also reveals that
      downstream target genes are regulated either positively or negatively by Oct3/4.
      Identification of a group of genes that show both activation and repression
      depending on Oct3/4 expression levels provides a possible mechanism for the
      requirement of appropriate Oct3/4 expression to maintain undifferentiated ES
      cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been
      analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and
      activates its transcription. We also show that Tcl1 is involved in the regulation
      of proliferation, but not differentiation, in ES cells. These findings suggest
      that the global expression profiling of gene-manipulated ES cells can help to
      delineate the structure and dynamics of gene regulatory networks.

PMID- 17183656
TI  - Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage
      apoptosis and activation.
AB  - Apoptosis and activation of macrophages play an important role in the host
      response to mycobacterial infection involving TNF-alpha as a critical autocrine
      mediator. The underlying mechanisms are still ill-defined. Here, we demonstrate
      elevated levels of methylglyoxal (MG), a small and reactive molecule that is
      usually a physiological product of various metabolic pathways, and advanced
      glycation end products (AGE) during mycobacterial infection of macrophages,
      leading to apoptosis and activation of macrophages. Moreover, we demonstrate
      abundant AGE in pulmonary lesions of tuberculosis (TB) patients. Global gene
      expression profiling of MG-treated macrophages revealed a diverse spectrum of
      functions induced by MG, including apoptosis and immune response. Our results not
      only provide first evidence for the involvement of MG and AGE in TB, but also
      form a basis for novel intervention strategies against infectious diseases in
      which MG and AGE play critical roles.

PMID- 17183657
TI  - Invasion and persistence of a selfish gene in the Cnidaria.
AB  - BACKGROUND: Homing endonuclease genes (HEGs) are superfluous, but are capable of
      invading populations that mix alleles by biasing their inheritance patterns
      through gene conversion. One model suggests that their long-term persistence is
      achieved through recurrent invasion. This circumvents evolutionary degeneration,
      but requires reasonable rates of transfer between species to maintain purifying
      selection. Although HEGs are found in a variety of microbes, we found the
      previous discovery of this type of selfish genetic element in the mitochondria of
      a sea anemone surprising. METHODS/PRINCIPAL FINDINGS: We surveyed 29 species of
      Cnidaria for the presence of the COXI HEG. Statistical analyses provided evidence
      for HEG invasion. We also found that 96 individuals of Metridium senile, from
      five different locations in the UK, had identical HEG sequences. This lack of
      sequence divergence illustrates the stable nature of Anthozoan mitochondria. Our
      data suggests this HEG conforms to the recurrent invasion model of evolution.
      CONCLUSIONS: Ordinarily such low rates of HEG transfer would likely be
      insufficient to enable major invasion. However, the slow rate of Anthozoan
      mitochondrial change lengthens greatly the time to HEG degeneration: this
      significantly extends the periodicity of the HEG life-cycle. We suggest that a
      combination of very low substitution rates and rare transfers facilitated
      metazoan HEG invasion.

PMID- 17183658
TI  - Triose phosphate isomerase deficiency is caused by altered dimerization--not
      catalytic inactivity--of the mutant enzymes.
AB  - Triosephosphate isomerase (TPI) deficiency is an autosomal recessive disorder
      caused by various mutations in the gene encoding the key glycolytic enzyme TPI. A
      drastic decrease in TPI activity and an increased level of its substrate,
      dihydroxyacetone phosphate, have been measured in unpurified cell extracts of
      affected individuals. These observations allowed concluding that the different
      mutations in the TPI alleles result in catalytically inactive enzymes. However,
      despite a high occurrence of TPI null alleles within several human populations,
      the frequency of this disorder is exceptionally rare. In order to address this
      apparent discrepancy, we generated a yeast model allowing us to perform
      comparative in vivo analyses of the enzymatic and functional properties of the
      different enzyme variants. We discovered that the majority of these variants
      exhibit no reduced catalytic activity per se. Instead, we observed, the
      dimerization behavior of TPI is influenced by the particular mutations
      investigated, and by the use of a potential alternative translation initiation
      site in the TPI gene. Additionally, we demonstrated that the overexpression of
      the most frequent TPI variant, Glu104Asp, which displays altered dimerization
      features, results in diminished endogenous TPI levels in mammalian cells. Thus,
      our results reveal that enzyme deregulation attributable to aberrant dimerization
      of TPI, rather than direct catalytic inactivation of the enzyme, underlies the
      pathogenesis of TPI deficiency. Finally, we discovered that yeast cells
      expressing a TPI variant exhibiting reduced catalytic activity are more resistant
      against oxidative stress caused by the thiol-oxidizing reagent diamide. This
      observed advantage might serve to explain the high allelic frequency of TPI null
      alleles detected among human populations.

PMID- 17183659
TI  - Human resistin is a systemic immune-derived proinflammatory cytokine targeting
      both leukocytes and adipocytes.
AB  - The characteristics of human resistin (RETN) are unclear and controversial
      despite intensive adipose-focused research. Its transcriptional and functional
      similarity with the murine myeloid-specific and CCAAT/enhancer binding protein
      epsilon (Cebpe)-dependent gene, resistin-like gamma (Retnlg), is unexplored. We
      examined the human CEBPE-regulatory pathway by unbiased reference and custom gene
      expression assays. Real-time RT-PCR analysis demonstrated lack of both the
      transcriptional factor CEBPE and RETN expression in adipose and muscle cells. In
      contrast, primary myelocytic samples revealed a concerted CEBPE-RETN
      transcription that was significantly elevated in inflammatory synoviocytes
      relative to intact peripheral blood mononuclear cells (PBMC). Mouse Cebpe and
      Retnlg were predictably expressed in macrophages, whereas Retn was abundant in
      adipocytes. Quite the opposite, a low and inconsistent RETN transcription was
      seen in some human white adipose tissue (WAT) biopsies without any relationship
      to body mass index, insulin sensitivity, or fat depot. However, in these cases,
      RETN was co-detected with CEBPE and the leukocyte-specific marker, EMR1,
      indicating the presence of inflammatory cells and their possible resistin
      mediated effect on adipocytes. Indeed, addition of human resistin to WAT in
      culture induced, like in PBMC, the inflammatory cytokines IL6, IL8 and TNF.
      Importantly, the expression of the adipose-specific markers CEBPA, FABP4 and
      SLC2A4 was unchanged, while the expected inhibitory effect was seen with TNF.
      Both cytokines increased the mRNA level of CCL2 and MMP3, which may further
      promote inflammation in WAT. Thus, the myeloid-restricted nature of CEBPE
      precludes the expression of RETN in human adipocytes which, however, are targeted
      by this innate immune-derived proinflammatory cytokine.

PMID- 17183660
TI  - A mouse stromal response to tumor invasion predicts prostate and breast cancer
      patient survival.
AB  - Primary and metastatic tumor growth induces host tissue responses that are
      believed to support tumor progression. Understanding the molecular changes within
      the tumor microenvironment during tumor progression may therefore be relevant not
      only for discovering potential therapeutic targets, but also for identifying
      putative molecular signatures that may improve tumor classification and predict
      clinical outcome. To selectively address stromal gene expression changes during
      cancer progression, we performed cDNA microarray analysis of laser-microdissected
      stromal cells derived from prostate intraepithelial neoplasia (PIN) and invasive
      cancer in a multistage model of prostate carcinogenesis. Human orthologs of genes
      identified in the stromal reaction to tumor progression in this mouse model were
      observed to be expressed in several human cancers, and to cluster prostate and
      breast cancer patients into groups with statistically different clinical
      outcomes. Univariate Cox analysis showed that overexpression of these genes is
      associated with shorter survival and recurrence-free periods. Taken together, our
      observations provide evidence that the expression signature of the stromal
      response to tumor invasion in a mouse tumor model can be used to probe human
      cancer, and to provide a powerful prognostic indicator for some of the most
      frequent human malignancies.

PMID- 17183661
TI  - A weakened transcriptional enhancer yields variegated gene expression.
AB  - Identical genes in the same cellular environment are sometimes expressed
      differently. In some cases, including the immunoglobulin heavy chain (IgH) locus,
      this type of differential gene expression has been related to the absence of a
      transcriptional enhancer. To gain additional information on the role of the IgH
      enhancer, we examined expression driven by enhancers that were merely weakened,
      rather than fully deleted, using both mutations and insulators to impair enhancer
      activity. For this purpose we used a LoxP/Cre system to place a reporter gene at
      the same genomic site of a stable cell line. Whereas expression of the reporter
      gene was uniformly high in the presence of the normal, uninsulated enhancer and
      undetectable in its absence, weakened enhancers yielded variegated expression of
      the reporter gene; i.e., the average level of expression of the same gene
      differed in different clones, and expression varied significantly among cells
      within individual clones. These results indicate that the weakened enhancer
      allows the reporter gene to exist in at least two states. Subtle aspects of the
      variegation suggest that the IgH enhancer decreases the average duration (half
      life) of the silent state. This analysis has also tested the conventional wisdom
      that enhancer activity is independent of distance and orientation. Thus, our
      analysis of mutant (truncated) forms of the IgH enhancer revealed that the 250 bp
      core enhancer was active in its normal position, approximately 1.4 kb 3' of the
      promoter, but inactive approximately 6 kb 3', indicating that the activity of the
      core enhancer was distance-dependent. A longer segment--the core enhancer plus
      approximately 1 kb of 3' flanking material, including the 3' matrix attachment
      region--was active, and the activity of this longer segment was orientation
      dependent. Our data suggest that this 3' flank includes binding sites for at
      least two activators.

PMID- 17183662
TI  - Electrochemically generated acid and its containment to 100 micron reaction areas
      for the production of DNA microarrays.
AB  - An addressable electrode array was used for the production of acid at sufficient
      concentration to allow deprotection of the dimethoxytrityl (DMT) protecting group
      from an overlaying substrate bound to a porous reaction layer. Containment of the
      generated acid to an active electrode of 100 micron diameter was achieved by the
      presence of an organic base. This procedure was then used for the production of a
      DNA array, in which synthesis was directed by the electrochemical removal of the
      DMT group during synthesis. The product array was found to have a detection
      sensitivity to as low as 0.5 pM DNA in a complex background sample.

PMID- 17183663
TI  - Restructuring of pancreatic islets and insulin secretion in a postnatal critical
      window.
AB  - Function and structure of adult pancreatic islets are determined by early
      postnatal development, which in rats corresponds to the first month of life. We
      analyzed changes in blood glucose and hormones during this stage and their
      association with morphological and functional changes of alpha and beta cell
      populations during this period. At day 20 (d20), insulin and glucose plasma
      levels were two- and six-fold higher, respectively, as compared to d6.
      Interestingly, this period is characterized by physiological hyperglycemia and
      hyperinsulinemia, where peripheral insulin resistance and a high plasmatic
      concentration of glucagon are also observed. These functional changes were
      paralleled by reorganization of islet structure, cell mass and aggregate size of
      alpha and beta cells. Cultured beta cells from d20 secreted the same amount of
      insulin in 15.6 mM than in 5.6 mM glucose (basal conditions), and were
      characterized by a high basal insulin secretion. However, beta cells from d28
      were already glucose sensitive. Understanding and establishing
      morphophysiological relationships in the developing endocrine pancreas may
      explain how events in early life are important in determining adult islet
      physiology and metabolism.

PMID- 17183664
TI  - Use of confocal laser as light source reveals stomata-autonomous function.
AB  - In most terrestrial plants, stomata open during the day to maximize the update of
      CO(2) for photosynthesis, but they close at night to minimize water loss. Blue
      light, among several environmental factors, controls this process. Stomata
      response to diverse stimuli seems to be dictated by the behaviour of neighbour
      stomata creating leaf areas of coordinated response. Here individual stomata of
      Arabidopsis leaves were illuminated with a short blue-light pulse by focusing a
      confocal argon laser. Beautifully, the illuminated stomata open their pores,
      whereas their dark-adapted neighbours unexpectedly experience no change. This
      induction of individual stomata opening by low fluence rates of blue light was
      disrupted in the phototropin1 phototropin2 (phot1 phot2) double mutant, which
      exhibits insensitivity of stomatal movements in blue-illuminated epidermal
      strips. The irradiation of all epidermal cells making direct contact with a given
      stoma in both wild type and phot1 phot2 plants does not trigger its movement.
      These results unravel the stoma autonomous function in the blue light response
      and illuminate the implication of PHOT1 and/or PHOT2 in such response. The micro
      spatial heterogeneity that solar blue light suffers in partially shaded leaves
      under natural conditions highlights the physiological significance of the
      autonomous stomatal behaviour.

PMID- 17183665
TI  - Ribosomal protein gene knockdown causes developmental defects in zebrafish.
AB  - The ribosomal proteins (RPs) form the majority of cellular proteins and are
      mandatory for cellular growth. RP genes have been linked, either directly or
      indirectly, to various diseases in humans. Mutations in RP genes are also
      associated with tissue-specific phenotypes, suggesting a possible role in organ
      development during early embryogenesis. However, it is not yet known how
      mutations in a particular RP gene result in specific cellular changes, or how RP
      genes might contribute to human diseases. The development of animal models with
      defects in RP genes will be essential for studying these questions. In this
      study, we knocked down 21 RP genes in zebrafish by using morpholino antisense
      oligos to inhibit their translation. Of these 21, knockdown of 19 RPs resulted in
      the development of morphants with obvious deformities. Although mutations in RP
      genes, like other housekeeping genes, would be expected to result in nonspecific
      developmental defects with widespread phenotypes, we found that knockdown of some
      RP genes resulted in phenotypes specific to each gene, with varying degrees of
      abnormality in the brain, body trunk, eyes, and ears at about 25 hours post
      fertilization. We focused further on the organogenesis of the brain. Each knocked
      down gene that affected the morphogenesis of the brain produced a different
      pattern of abnormality. Among the 7 RP genes whose knockdown produced severe
      brain phenotypes, 3 human orthologs are located within chromosomal regions that
      have been linked to brain-associated diseases, suggesting a possible involvement
      of RP genes in brain or neurological diseases. The RP gene knockdown system
      developed in this study could be a powerful tool for studying the roles of
      ribosomes in human diseases.

PMID- 17183667
TI  - A virtual reprise of the Stanley Milgram obedience experiments.
AB  - BACKGROUND: Stanley Milgram's 1960s experimental findings that people would
      administer apparently lethal electric shocks to a stranger at the behest of an
      authority figure remain critical for understanding obedience. Yet, due to the
      ethical controversy that his experiments ignited, it is nowadays impossible to
      carry out direct experimental studies in this area. In the study reported in this
      paper, we have used a similar paradigm to the one used by Milgram within an
      immersive virtual environment. Our objective has not been the study of obedience
      in itself, but of the extent to which participants would respond to such an
      extreme social situation as if it were real in spite of their knowledge that no
      real events were taking place. METHODOLOGY: Following the style of the original
      experiments, the participants were invited to administer a series of word
      association memory tests to the (female) virtual human representing the stranger.
      When she gave an incorrect answer, the participants were instructed to administer
      an 'electric shock' to her, increasing the voltage each time. She responded with
      increasing discomfort and protests, eventually demanding termination of the
      experiment. Of the 34 participants, 23 saw and heard the virtual human, and 11
      communicated with her only through a text interface. CONCLUSIONS: Our results
      show that in spite of the fact that all participants knew for sure that neither
      the stranger nor the shocks were real, the participants who saw and heard her
      tended to respond to the situation at the subjective, behavioural and
      physiological levels as if it were real. This result reopens the door to direct
      empirical studies of obedience and related extreme social situations, an area of
      research that is otherwise not open to experimental study for ethical reasons,
      through the employment of virtual environments.

PMID- 17183666
TI  - Efficient non-viral ocular gene transfer with compacted DNA nanoparticles.
AB  - BACKGROUND: The eye is an excellent candidate for gene therapy as it is immune
      privileged and much of the disease-causing genetics are well understood. Towards
      this goal, we evaluated the efficiency of compacted DNA nanoparticles as a system
      for non-viral gene transfer to ocular tissues. The compacted DNA nanoparticles
      examined here have been shown to be safe and effective in a human clinical trial,
      have no theoretical limitation on plasmid size, do not provoke immune responses,
      and can be highly concentrated. METHODS AND FINDINGS: Here we show that these
      nanoparticles can be targeted to different tissues within the eye by varying the
      site of injection. Almost all cell types of the eye were capable of transfection
      by the nanoparticle and produced robust levels of gene expression that were dose
      dependent. Most impressively, subretinal delivery of these nanoparticles
      transfected nearly all of the photoreceptor population and produced expression
      levels almost equal to that of rod opsin, the highest expressed gene in the
      retina. CONCLUSIONS: As no deleterious effects on retinal function were observed,
      this treatment strategy appears to be clinically viable and provides a highly
      efficient non-viral technology to safely deliver and express nucleic acids in the
      retina and other ocular tissues.

PMID- 17183668
TI  - Expression of transgenes targeted to the Gt(ROSA)26Sor locus is orientation
      dependent.
AB  - BACKGROUND: Targeting transgenes to a chosen location in the genome has a number
      of advantages. A single copy of the DNA construct can be inserted by targeting
      into regions of chromatin that allow the desired developmental and tissue
      specific expression of the transgene. METHODOLOGY: In order to develop a reliable
      system for reproducibly expressing transgenes it was decided to insert constructs
      at the Gt(ROSA)26Sor locus. A cytomegalovirus (CMV) promoter was used to drive
      expression of the Tetracycline (tet) transcriptional activator, rtTA2(s)-M2, and
      test the effectiveness of using the ROSA26 locus to allow transgene expression.
      The tet operator construct was inserted into one allele of ROSA26 and a tet
      responder construct controlling expression of EGFP was inserted into the other
      allele. CONCLUSIONS: Expression of the targeted transgenes was shown to be
      affected by both the presence of selectable marker cassettes and by the
      orientation of the transgenes with respect to the endogenous ROSA26 promoter.
      These results suggest that transcriptional interference from the endogenous gene
      promoter or from promoters in the selectable marker cassettes may be affecting
      transgene expression at the locus. Additionally we have been able to determine
      the optimal orientation for transgene expression at the ROSA26 locus.

PMID- 17183669
TI  - Mapping the antigenicity of the parasites in Leishmania donovani infection by
      proteome serology.
AB  - BACKGROUND: Leishmaniasis defines a cluster of protozoal diseases with diverse
      clinical manifestations. The visceral form caused by Leishmania donovani is the
      most severe. So far, no vaccines exist for visceral leishmaniasis despite
      indications of naturally developing immunity, and sensitive immunodiagnostics are
      still at early stages of development. METHODOLOGY/PRINCIPLE FINDINGS:
      Establishing a proteome-serological methodology, we mapped the antigenicity of
      the parasites and the specificities of the immune responses in human
      leishmaniasis. Using 2-dimensional Western blot analyses with sera and parasites
      isolated from patients in India, we detected immune responses with widely
      divergent specificities for up to 330 different leishmanial antigens. 68 antigens
      were assigned to proteins in silver- and fluorochrome-stained gels. The
      antigenicity of these proteins did not correlate with the expression levels of
      the proteins. Although some antigens are shared among different parasite
      isolates, there are extensive differences and no immunodominant antigens, but
      indications of antigenic drift in the parasites. Six antigens were identified by
      mass spectrometry. CONCLUSIONS/SIGNIFICANCE: Proteomics-based dissection of the
      serospecificities of leishmaniasis patients provides a comprehensive inventory of
      the complexity and interindividual heterogeneity of the host-responses to and
      variations in the antigenicity of the Leishmania parasites. This information can
      be instrumental in the development of vaccines and new immune monitoring and
      diagnostic devices.

PMID- 17183670
TI  - Association and host selectivity in multi-host pathogens.
AB  - The distribution of multi-host pathogens over their host range conditions their
      population dynamics and structure. Also, host co-infection by different pathogens
      may have important consequences for the evolution of hosts and pathogens, and
      host-pathogen co-evolution. Hence it is of interest to know if the distribution
      of pathogens over their host range is random, or if there are associations
      between hosts and pathogens, or between pathogens sharing a host. To analyse
      these issues we propose indices for the observed patterns of host infection by
      pathogens, and for the observed patterns of co-infection, and tests to analyse if
      these patterns conform to randomness or reflect associations. Applying these
      tests to the prevalence of five plant viruses on 21 wild plant species evidenced
      host-virus associations: most hosts and viruses were selective for viruses and
      hosts, respectively. Interestingly, the more host-selective viruses were the more
      prevalent ones, suggesting that host specialisation is a successful strategy for
      multi-host pathogens. Analyses also showed that viruses tended to associate
      positively in co-infected hosts. The developed indices and tests provide the
      tools to analyse how strong and common are these associations among different
      groups of pathogens, which will help to understand and model the population
      biology of multi-host pathogens.

PMID- 17183671
TI  - A uniform genomic minor histocompatibility antigen typing methodology and
      database designed to facilitate clinical applications.
AB  - BACKGROUND: Minor Histocompatibility (H) antigen mismatches significantly
      influence the outcome of HLA-matched allogeneic stem cell transplantation. The
      molecular identification of human H antigens is increasing rapidly. In parallel,
      clinical application of minor H antigen typing has gained interest. So far,
      relevant and simple tools to analyze the minor H antigens in a quick and reliable
      way are lacking. METHODOLOGY AND FINDINGS: We developed a uniform PCR with
      sequence-specific primers (PCR-SSP) for 10 different autosomal minor H antigens
      and H-Y. This genomic minor H antigen typing methodology allows easy
      incorporation in the routine HLA typing procedures. DNA from previously typed EBV
      LCL was used to validate the methodology. To facilitate easy interpretation for
      clinical purposes, a minor H database named dbMinor (http://www.lumc.nl/dbminor)
      was developed. Input of the minor H antigen typing results subsequently provides
      all relevant information for a given patient/donor pair and additional
      information on the putative graft-versus-host, graft-versus-tumor and host-versus
      graft reactivities. SIGNIFICANCE: A simple, uniform and rapid methodology was
      developed enabling determination of minor H antigen genotypes of all currently
      identified minor H antigens. A dbMinor database was developed to interpret the
      genomic typing for its potential clinical relevance. The combination of the minor
      H antigen genomic typing methodology with the online dbMinor database and
      applications facilitates the clinical application of minor H antigens anti-tumor
      targets after stem cell transplantation.

PMID- 17183672
TI  - Is adipose tissue a place for Mycobacterium tuberculosis persistence?
AB  - BACKGROUND: Mycobacterium tuberculosis, the etiological agent of tuberculosis
      (TB), has the ability to persist in its human host for exceptionally long periods
      of time. However, little is known about the location of the bacilli in latently
      infected individuals. Long-term mycobacterial persistence in the lungs has been
      reported, but this may not sufficiently account for strictly extra-pulmonary TB,
      which represents 10-15% of the reactivation cases. METHODOLOGY/PRINCIPAL
      FINDINGS: We applied in situ and conventional PCR to sections of adipose tissue
      samples of various anatomical origins from 19 individuals from Mexico and 20 from
      France who had died from causes other than TB. M. tuberculosis DNA could be
      detected by either or both techniques in fat tissue surrounding the kidneys, the
      stomach, the lymph nodes, the heart and the skin in 9/57 Mexican samples (6/19
      individuals), and in 8/26 French samples (6/20 individuals). In addition,
      mycobacteria could be immuno-detected in perinodal adipose tissue of 1 out of 3
      biopsy samples from individuals with active TB. In vitro, using a combination of
      adipose cell models, including the widely used murine adipose cell line 3T3-L1,
      as well as primary human adipocytes, we show that after binding to scavenger
      receptors, M. tuberculosis can enter within adipocytes, where it accumulates
      intracytoplasmic lipid inclusions and survives in a non-replicating state that is
      insensitive to the major anti-mycobacterial drug isoniazid.
      CONCLUSIONS/SIGNIFICANCE: Given the abundance and the wide distribution of the
      adipose tissue throughout the body, our results suggest that this tissue, among
      others, might constitute a vast reservoir where the tubercle bacillus could
      persist for long periods of time, and avoid both killing by antimicrobials and
      recognition by the host immune system. In addition, M. tuberculosis-infected
      adipocytes might provide a new model to investigate dormancy and to evaluate new
      drugs for the treatment of persistent infection.

PMID- 17183674
TI  - Predator mimicry: metalmark moths mimic their jumping spider predators.
AB  - Cases of mimicry provide many of the nature's most convincing examples of natural
      selection. Here we report evidence for a case of predator mimicry in which
      metalmark moths in the genus Brenthia mimic jumping spiders, one of their
      predators. In controlled trials, Brenthia had higher survival rates than other
      similarly sized moths in the presence of jumping spiders and jumping spiders
      responded to Brenthia with territorial displays, indicating that Brenthia were
      sometimes mistaken for jumping spiders, and not recognized as prey. Our
      experimental results and a review of wing patterns of other insects indicate that
      jumping spider mimicry is more widespread than heretofore appreciated, and that
      jumping spiders are probably an important selective pressure shaping the
      evolution of diurnal insects that perch on vegetation.

PMID- 17183673
TI  - A new family of giardial cysteine-rich non-VSP protein genes and a novel cyst
      protein.
AB  - Since the Giardia lamblia cyst wall is necessary for survival in the environment
      and host infection, we tested the hypothesis that it contains proteins other than
      the three known cyst wall proteins. Serial analysis of gene expression during
      growth and encystation revealed a gene, "HCNCp" (High Cysteine Non-variant Cyst
      protein), that was upregulated late in encystation, and that resembled the
      classic Giardia variable surface proteins (VSPs) that cover the trophozoite
      plasmalemma. HCNCp is 13.9% cysteine, with many "CxxC" tetrapeptide motifs and a
      transmembrane sequence near the C-terminus. However, HCNCp has multiple "CxC"
      motifs rarely found in VSPs, and does not localize to the trophozoite
      plasmalemma. Moreover, the HCNCp C-terminus differed from the canonical VSP
      signature. Full-length epitope-tagged HCNCp expressed under its own promoter was
      upregulated during encystation with highest expression in cysts, including 42 and
      21 kDa C-terminal fragments. Tagged HCNCp targeted to the nuclear envelope in
      trophozoites, and co-localized with cyst proteins to encystation-specific
      secretory vesicles during encystation. HCNCp defined a novel trafficking pathway
      as it localized to the wall and body of cysts, while the cyst proteins were
      exclusively in the wall. Unlike VSPs, HCNCp is expressed in at least five
      giardial strains and four WB subclones expressing different VSPs. Bioinformatics
      identified 60 additional large high cysteine membrane proteins (HCMp) containing
      > or = 20 CxxC/CxC's lacking the VSP-specific C-terminal CRGKA. HCMp were absent
      or rare in other model or parasite genomes, except for Tetrahymena thermophila
      with 30. MEME analysis classified the 61 gHCMp genes into nine groups with
      similar internal motifs. Our data suggest that HCNCp is a novel invariant cyst
      protein belonging to a new HCMp family that is abundant in the Giardia genome.
      HCNCp and the other HCMp provide a rich source for developing parasite-specific
      diagnostic reagents, vaccine candidates, and subjects for further research into
      Giardia biology.

PMID- 17183675
TI  - Fine tuning of globin gene expression by DNA methylation.
AB  - Expression patterns in the globin gene cluster are subject to developmental
      regulation in vivo. While the gamma(A) and gamma(G) genes are expressed in fetal
      liver, both are silenced in adult erythrocytes. In order to decipher the role of
      DNA methylation in this process, we generated a YAC transgenic mouse system that
      allowed us to control gamma(A) methylation during development. DNA methylation
      causes a 20-fold repression of gamma(A) both in non-erythroid and adult erythroid
      cells. In erythroid cells this modification works as a dominant mechanism to
      repress gamma gene expression, probably through changes in histone acetylation
      that prevent the binding of erythroid transcription factors to the promoter.
      These studies demonstrate that DNA methylation serves as an elegant in vivo fine
      tuning device for selecting appropriate genes in the globin locus. In addition,
      our findings provide a mechanism for understanding the high levels of gamma
      globin transcription seen in patients with Hereditary Persistence of Fetal
      Hemoglobin, and help explain why 5azaC and butyrate compounds stimulate gamma
      globin expression in patients with beta-hemoglobinopathies.

PMID- 17183677
TI  - Does FXIII deficiency impair wound healing after myocardial infarction?
AB  - Inadequate healing of myocardial infarction may contribute to local expansion of
      the infarct, frequently leading to chamber dilation, heart failure, or myocardial
      rupture. Experimental evidence in mouse models suggests that Factor XIII might
      play a key role in wound healing, and low persistent values lead to increased
      incidence of cardiac rupture following myocardial infarction. Here we would like
      to share our initial clinical experiences with strikingly similar observations in
      patients with this grave disease, and compare these observations to experimental
      findings.

PMID- 17183679
TI  - Concentration of the most-cited papers in the scientific literature: analysis of
      journal ecosystems.
AB  - BACKGROUND: A minority of scientific journals publishes the majority of
      scientific papers and receives the majority of citations. The extent of
      concentration of the most influential articles is less well known.
      METHODS/PRINCIPAL FINDINGS: The 100 most-cited papers in the last decade in each
      of 21 scientific fields were analyzed; fields were considered as ecosystems and
      their "species" (journal) diversity was evaluated. Only 9% of journals in Journal
      Citation Reports had published at least one such paper. Among this 9%, half of
      them had published only one such paper. The number of journals that had published
      a larger number of most-cited papers decreased exponentially according to a Lotka
      law. Except for three scientific fields, six journals accounted for 53 to 94 of
      the 100 most-cited papers in their field. With increasing average number of
      citations per paper (citation density) in a scientific field, concentration of
      the most-cited papers in a few journals became even more prominent (p<0.001).
      Concentration was unrelated to the number of papers published or number of
      journals available in a scientific field. Multidisciplinary journals accounted
      for 24% of all most-cited papers, with large variability across fields. The
      concentration of most-cited papers in multidisciplinary journals was most
      prominent in fields with high citation density (correlation coefficient 0.70,
      p<0.001). Multidisciplinary journals had published fewer than eight of the 100
      most-cited papers in eight scientific fields (none in two fields). Journals
      concentrating most-cited original articles often differed from those
      concentrating most-cited reviews. The concentration of the most-influential
      papers was stronger than the already prominent concentration of papers published
      and citations received. CONCLUSIONS: Despite a plethora of available journals,
      the most influential papers are extremely concentrated in few journals,
      especially in fields with high citation density. Existing multidisciplinary
      journals publish selectively most-cited papers from fields with high citation
      density.

PMID- 17183678
TI  - Adaptive response of a gene network to environmental changes by fitness-induced
      attractor selection.
AB  - Cells switch between various stable genetic programs (attractors) to accommodate
      environmental conditions. Signal transduction machineries efficiently convey
      environmental changes to the gene regulation apparatus in order to express the
      appropriate genetic program. However, since the number of environmental
      conditions is much larger than that of available genetic programs so that the
      cell may utilize the same genetic program for a large set of conditions, it may
      not have evolved a signaling pathway for every environmental condition, notably
      those that are rarely encountered. Here we show that in the absence of signal
      transduction, switching to the appropriate attractor state expressing the genes
      that afford adaptation to the external condition can occur. In a synthetic
      bistable gene switch in Escherichia coli in which mutually inhibitory operons
      govern the expression of two genes required in two alternative nutritional
      environments, cells reliably selected the "adaptive attractor" driven by gene
      expression noise. A mathematical model suggests that the "non-adaptive attractor"
      is avoided because in unfavorable conditions, cellular activity is lower, which
      suppresses mRNA metabolism, leading to larger fluctuations in gene expression.
      This, in turn, renders the non-adaptive state less stable. Although attractor
      selection is not as efficient as signal transduction via a dedicated cascade, it
      is simple and robust, and may represent a primordial mechanism for adaptive
      responses that preceded the evolution of signaling cascades for the frequently
      encountered environmental changes.

PMID- 17183676
TI  - Cdx4 and menin co-regulate Hoxa9 expression in hematopoietic cells.
AB  - BACKGROUND: Transcription factor Cdx4 and transcriptional coregulator menin are
      essential for Hoxa9 expression and normal hematopoiesis. However, the precise
      mechanism underlying Hoxa9 regulation is not clear. METHODS AND FINDINGS: Here,
      we show that the expression level of Hoxa9 is correlated with the location of
      increased trimethylated histone 3 lysine 4 (H3K4M3). The active and repressive
      histone modifications co-exist along the Hoxa9 regulatory region. We further
      demonstrate that both Cdx4 and menin bind to the same regulatory region at the
      Hoxa9 locus in vivo, and co-activate the reporter gene driven by the Hoxa9 cis
      elements that contain Cdx4 binding sites. Ablation of menin abrogates Cdx4 access
      to the chromatin target and significantly reduces both active and repressive
      histone H3 modifications in the Hoxa9 locus. CONCLUSION: These results suggest a
      functional link among Cdx4, menin and histone modifications in Hoxa9 regulation
      in hematopoietic cells.

PMID- 17183680
TI  - Human natural killer T cells are heterogeneous in their capacity to reprogram
      their effector functions.
AB  - BACKGROUND: Natural killer T (NKT) cells are a subset of T cells that help
      potentiate and regulate immune responses. Although human NKT cell subsets with
      distinct effector functions have been identified, it is unclear whether the
      effector functions of these subsets are imprinted during development or can be
      selectively reprogrammed in the periphery. RESULTS: We found that neonatal NKT
      cells are predominantly CD4+ and express higher levels of CCR7 and CD62L and
      lower levels of CD94 and CD161 than adult CD4+ or CD4- NKT cell subsets.
      Accordingly, neonatal NKT cells were more flexible than adult CD4+ NKT cells in
      their capacity to acquire Th1- or Th2-like functions upon either cytokine
      mediated polarization or ectopic expression of the Th1 or Th2 transcription
      factors T-bet and GATA-3, respectively. Consistent with their more differentiated
      phenotype, CD4- NKT cells were predominantly resistant to functional
      reprogramming and displayed higher cytotoxic function. In contrast to
      conventional T cells, neither the expression of CXCR3 nor the cytotoxic capacity
      of neonatal NKT cells could be reprogrammed. CONCLUSIONS AND SIGNIFICANCE:
      Together, these results suggest that neonatal CD4+, adult CD4+, and adult CD4-
      NKT may represent unique states of maturation and that some functions of human
      NKT cells may be developmentally imprinted, while others are acquired similar to
      conventional T cell subsets during peripheral maturation and differentiation.
      Given the potent immuno-regulatory functions of NKT cells, these findings have
      important implications for the development of novel NKT cell-based therapeutics
      and vaccines.

PMID- 17183681
TI  - Physiological mouse brain Abeta levels are not related to the phosphorylation
      state of threonine-668 of Alzheimer's APP.
AB  - BACKGROUND: Amyloid-beta peptide species ending at positions 40 and 42 (Abeta40,
      Abeta42) are generated by the proteolytic processing of the Alzheimer's amyloid
      precursor protein (APP). Abeta peptides accumulate in the brain early in the
      course of Alzheimer's disease (AD), especially Abeta42. The cytoplasmic domain of
      APP regulates intracellular trafficking and metabolism of APP and its carboxyl
      terminal fragments (CTFalpha, CTFbeta). The role of protein phosphorylation in
      general, and that of the phosphorylation state of APP at threonine-668 (Thr668)
      in particular, has been investigated in detail by several laboratories (including
      our own). Some investigators have recently proposed that the phosphorylation
      state of Thr668 plays a pivotal role in governing brain Abeta levels, prompting
      the current study. METHODOLOGY: In order to evaluate whether the phosphorylation
      state of Thr668 controlled brain Abeta levels, we studied the levels and
      subcellular distributions of holoAPP, sAPPalpha, sAPPbeta, CTFalpha, CTFbeta,
      Abeta40 and Abeta42 in brains from "knock-in" mice in which a non
      phosphorylatable alanyl residue had been substituted at position 668, replacing
      the threonyl residue present in the wild-type protein. CONCLUSIONS: The levels
      and subcellular distributions of holoAPP, sAPPalpha, sAPPbeta, CTFalpha, CTFbeta,
      Abeta40 and Abeta42 in the brains of Thr668Ala mutant mice were identical to
      those observed in wild-type mice. These results indicate that, despite
      speculation to the contrary, the phosphorylation state of APP at Thr668 does not
      play an obvious role in governing the physiological levels of brain Abeta40 or
      Abeta42 in vivo.

PMID- 17183682
TI  - Impact of neuroprotection on incidence of Alzheimer's disease.
AB  - Converging evidence suggests that high levels of education and intellectual
      activity increase the cognitive reserve and reduce the risk of dementia. However,
      little is known about the impact that different neuroprotective strategies may
      have on the incidence of Alzheimer's disease. Using a simple mathematical
      regression model, it is shown here that age-specific counts of basic cognitive
      units (surrogate of neurons or synapses) in the normal population can be
      estimated from Alzheimer's incidence rates. Hence, the model can be used to test
      the effect of neuroprotection on Alzheimer's incidence. It was found that the
      number of basic cognitive units decreases with age, but levels off in older
      people. There were no gender differences after correcting for survival. The model
      shows that even modest neuroprotective effects on basic cognitive units can lead
      to dramatic reductions in the number of Alzheimer's cases. Most remarkably, a 5%
      increase in the cognitive reserve would prevent one third of Alzheimer's cases.
      These results suggest that public health policies aimed at increasing the
      cognitive reserve in the general population (e.g., implementing higher levels of
      education) are likely the most effective strategy for preventing Alzheimer's
      disease.

PMID- 17183683
TI  - PIASgamma is required for faithful chromosome segregation in human cells.
AB  - BACKGROUND: The precision of the metaphase-anaphase transition ensures stable
      genetic inheritance. The spindle checkpoint blocks anaphase onset until the last
      chromosome biorients at metaphase plate, then the bonds between sister chromatids
      are removed and disjoined chromatids segregate to the spindle poles. But, how
      sister separation is triggered is not fully understood. PRINCIPAL FINDINGS: We
      identify PIASgamma as a human E3 sumo ligase required for timely and efficient
      sister chromatid separation. In cells lacking PIASgamma, normal metaphase plates
      form, but the spindle checkpoint is activated, leading to a prolonged metaphase
      block. Sister chromatids remain cohered even if cohesin is removed by depletion
      of hSgo1, because DNA catenations persist at centromeres. PIASgamma-depleted
      cells cannot properly localize Topoisomerase II at centromeres or in the cores of
      mitotic chromosomes, providing a functional link between PIASgamma and
      Topoisomerase II. CONCLUSIONS: PIASgamma directs Topoisomerase II to specific
      chromosome regions that require efficient removal of DNA catenations prior to
      anaphase. The lack of this activity activates the spindle checkpoint, protecting
      cells from non-disjunction. Because DNA catenations persist without PIASgamma in
      the absence of cohesin, removal of catenations and cohesin rings must be
      regulated in parallel.

PMID- 17183684
TI  - The dark side of EGFP: defective polyubiquitination.
AB  - Enhanced Green Fluorescent Protein (EGFP) is the most commonly used live cell
      reporter despite a number of conflicting reports that it can affect cell
      physiology. Thus far, the precise mechanism of GFP-associated defects remained
      unclear. Here we demonstrate that EGFP and EGFP fusion proteins inhibit
      polyubiquitination, a posttranslational modification that controls a wide variety
      of cellular processes, like activation of kinase signalling or protein
      degradation by the proteasome. As a consequence, the NF-kappaB and JNK signalling
      pathways are less responsive to activation, and the stability of the p53 tumour
      suppressor is enhanced in cell lines and in vivo. In view of the emerging role of
      polyubiquitination in the regulation of numerous cellular processes, the use of
      EGFP as a live cell reporter should be carefully considered.

PMID- 17183685
TI  - Monitoring the T-cell receptor repertoire at single-clone resolution.
AB  - The adaptive immune system recognizes billions of unique antigens using highly
      variable T-cell receptors. The alphabeta T-cell receptor repertoire includes an
      estimated 10(6) different rearranged beta chains per individual. This paper
      describes a novel micro-array based method that monitors the beta chain
      repertoire with a resolution of a single T-cell clone. These T-arrays are
      quantitative and detect T-cell clones at a frequency of less than one T cell in a
      million, which is 2 logs more sensitive than spectratyping (immunoscope), the
      current standard in repertoire analysis. Using T-arrays we detected CMV-specific
      CD4+ and CD8+ T-cell clones that expanded early after viral antigen stimulation
      in vitro and in vivo. This approach will be useful in monitoring individual T
      cell clones in diverse experimental settings, and in identification of T-cell
      clones associated with infectious disease, autoimmune disease and cancer.

PMID- 17183686
TI  - A low protein diet increases the hypoxic tolerance in Drosophila.
AB  - Dietary restriction is well known to increase the life span of a variety of
      organisms from yeast to mammals, but the relationships between nutrition and the
      hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell
      death in myocardial infarction and stroke. Here we forced hypoxia-related death
      by exposing one-day-old male Drosophila to chronic hypoxia (5% O(2)) and analysed
      their survival. Chronic hypoxia reduced the average life span from 33.6 days to
      6.3 days when flies were fed on a rich diet. A demographic analysis indicated
      that chronic hypoxia increased the slope of the mortality trajectory and not the
      short-term risk of death. Dietary restriction produced by food dilution, by yeast
      restriction, or by amino acid restriction partially reversed the deleterious
      action of hypoxia. It increased the life span of hypoxic flies up to seven days,
      which represented about 25% of the life time of an hypoxic fly. Maximum survival
      of hypoxic flies required only dietary sucrose, and it was insensitive to drugs
      such as rapamycin and resveratrol, which increase longevity of normoxic animals.
      The results thus uncover a new link between protein nutrition, nutrient
      signalling, and resistance to hypoxic stresses.

PMID- 17183687
TI  - Genes from Chagas susceptibility loci that are differentially expressed in T.
      cruzi-resistant mice are candidates accounting for impaired immunity.
AB  - Variation between inbred mice of susceptibility to experimental Trypanosoma cruzi
      infection has frequently been described, but the immunogenetic background is
      poorly understood. The outcross of the susceptible parental mouse strains C57BL/6
      (B6) and DBA/2 (D2), B6D2F1 (F1) mice, is highly resistant to this parasite. In
      the present study we show by quantitative PCR that the increase of tissue
      parasitism during the early phase of infection is comparable up to day 11 between
      susceptible B6 and resistant F1 mice. A reduction of splenic parasite burdens
      occurs thereafter in both strains but is comparatively retarded in susceptible
      mice. Splenic microarchitecture is progressively disrupted with loss of follicles
      and B lymphocytes in B6 mice, but not in F1 mice. By genotyping of additional
      backcross offspring we corroborate our earlier findings that susceptibility maps
      to three loci on Chromosomes 5, 13 and 17. Analysis of gene expression of spleen
      cells from infected B6 and F1 mice with microarrays identifies about 0.3% of
      transcripts that are differentially expressed. Assuming that differential
      susceptibility is mediated by altered gene expression, we propose that the
      following differentially expressed transcripts from these loci are strong
      candidates for the observed phenotypic variation: H2-Ealpha, H2-D1, Ng23, Msh5
      and Tubb5 from Chromosome 17; and Cxcl11, Bmp2k and Spp1 from Chromosome 5. Our
      results indicate that innate mechanisms are not of primary relevance to
      resistance of F1 mice to T. cruzi infection, and that differential susceptibility
      to experimental infection with this protozoan pathogen is not paralleled by
      extensive variation of the transcriptome.

PMID- 17183688
TI  - Novel acetylcholinesterase target site for malaria mosquito control.
AB  - Current anticholinesterase pesticides were developed during World War II and are
      toxic to mammals because they target a catalytic serine residue of
      acetylcholinesterases (AChEs) in insects and in mammals. A sequence analysis of
      AChEs from 73 species and a three-dimensional model of a malaria-carrying
      mosquito (Anopheles gambiae) AChE (AgAChE) reported here show that C286 and R339
      of AgAChE are conserved at the opening of the active site of AChEs in 17
      invertebrate and four insect species, respectively. Both residues are absent in
      the active site of AChEs of human, monkey, dog, cat, cattle, rabbit, rat, and
      mouse. The 17 invertebrates include house mosquito, Japanese encephalitis
      mosquito, African malaria mosquito, German cockroach, Florida lancelet, rice leaf
      beetle, African bollworm, beet armyworm, codling moth, diamondback moth, domestic
      silkworm, honey bee, oat or wheat aphid, the greenbug, melon or cotton aphid,
      green peach aphid, and English grain aphid. The four insects are house mosquito,
      Japanese encephalitis mosquito, African malaria mosquito, and German cockroach.
      The discovery of the two invertebrate-specific residues enables the development
      of effective and safer pesticides that target the residues present only in
      mosquito AChEs rather than the ubiquitous serine residue, thus potentially
      offering an effective control of mosquito-borne malaria. Anti-AgAChE pesticides
      can be designed to interact with R339 and subsequently covalently bond to C286.
      Such pesticides would be toxic to mosquitoes but not to mammals.

PMID- 17183689
TI  - Taxonomic reliability of DNA sequences in public sequence databases: a fungal
      perspective.
AB  - BACKGROUND: DNA sequences are increasingly seen as one of the primary information
      sources for species identification in many organism groups. Such approaches,
      popularly known as barcoding, are underpinned by the assumption that the
      reference databases used for comparison are sufficiently complete and feature
      correctly and informatively annotated entries. METHODOLOGY/PRINCIPAL FINDINGS:
      The present study uses a large set of fungal DNA sequences from the inclusive
      International Nucleotide Sequence Database to show that the taxon sampling of
      fungi is far from complete, that about 20% of the entries may be incorrectly
      identified to species level, and that the majority of entries lack descriptive
      and up-to-date annotations. CONCLUSIONS: The problems with taxonomic reliability
      and insufficient annotations in public DNA repositories form a tangible obstacle
      to sequence-based species identification, and it is manifest that the greatest
      challenges to biological barcoding will be of taxonomical, rather than technical,
      nature.

PMID- 17183690
TI  - Establishing clonal cell lines with endothelial-like potential from CD9(hi), SSEA
      1(-) cells in embryonic stem cell-derived embryoid bodies.
AB  - BACKGROUND: Differentiation of embryonic stem cells (ESCs) into specific cell
      types with minimal risk of teratoma formation could be efficiently directed by
      first reducing the differentiation potential of ESCs through the generation of
      clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate
      these stem cells are, however, mired in an impasse where the lack of purified
      lineage-restricted stem cells has hindered the identification of defining markers
      for these rare stem cells and, in turn, their isolation. METHODOLOGY/PRINCIPAL
      FINDINGS: We describe here a method for the isolation of clonal lineage
      restricted cell lines with endothelial potential from ESCs through a combination
      of empirical and rational evidence-based methods. Using an empirical protocol
      that we have previously developed to generate embryo-derived RoSH lines with
      endothelial potential, we first generated E-RoSH lines from mouse ESC-derived
      embryoid bodies (EBs). Despite originating from different mouse strains, RoSH and
      E- RoSH lines have similar gene expression profiles (r(2) = 0.93) while that
      between E-RoSH and ESCs was 0.83. In silico gene expression analysis predicted
      that like RoSH cells, E-RoSH cells have an increased propensity to differentiate
      into vasculature. Unlike their parental ESCs, E-RoSH cells did not form teratomas
      and differentiate efficiently into endothelial-like cells in vivo and in vitro.
      Gene expression and FACS analysis revealed that RoSH and E-RoSH cells are
      CD9(hi), SSEA-1(-) while ESCs are CD9(lo), SSEA-1(+). Isolation of CD9(hi), SSEA
      1(-) cells that constituted 1%-10% of EB-derived cultures generated an E-RoSH
      like culture with an identical E-RoSH-like gene expression profile (r(2) = 0.95)
      and a propensity to differentiate into endothelial-like cells. CONCLUSIONS: By
      combining empirical and rational evidence-based methods, we identified definitive
      selectable surface antigens for the isolation and propagation of lineage
      restricted stem cells with endothelial-like potential from mouse ESCs.

PMID- 17183691
TI  - A large specific deterrent effect of arrest for patronizing a prostitute.
AB  - BACKGROUND: Prior research suggests that arrest, compared with no police
      detection, of some types of offenders does not decrease the chances they will
      reoffend. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the specific deterrent
      effect of arrest for patronizing a street prostitute in Colorado Springs by
      comparing the incidence of arrest for clients of prostitutes first detected
      through public health surveillance with the incidence of rearrest for clients
      first detected by police arrest. Although these sets of clients were
      demographically and behaviorally similar, arrest reduced the likelihood of a
      subsequent arrest by approximately 70%. In other areas of the United States,
      arrest did not appear to displace a client's patronizing.
      CONCLUSIONS/SIGNIFICANCE: Our results suggest that apprehending clients decreases
      their patronizing behavior substantially.

PMID- 17183693
TI  - Sexual selection and the evolution of brain size in primates.
AB  - Reproductive competition among males has long been considered a powerful force in
      the evolution of primates. The evolution of brain size and complexity in the
      Order Primates has been widely regarded as the hallmark of primate evolutionary
      history. Despite their importance to our understanding of primate evolution, the
      relationship between sexual selection and the evolutionary development of brain
      size is not well studied. The present research examines the evolutionary
      relationship between brain size and two components of primate sexual selection,
      sperm competition and male competition for mates. Results indicate that there is
      not a significant relationship between relative brain size and sperm competition
      as measured by relative testis size in primates, suggesting sperm competition has
      not played an important role in the evolution of brain size in the primate order.
      There is, however, a significant negative evolutionary relationship between
      relative brain size and the level of male competition for mates. The present
      study shows that the largest relative brain sizes among primate species are
      associated with monogamous mating systems, suggesting primate monogamy may
      require greater social acuity and abilities of deception.

PMID- 17183692
TI  - Self-correcting maps of molecular pathways.
AB  - Reliable and comprehensive maps of molecular pathways are indispensable for
      guiding complex biomedical experiments. Such maps are typically assembled from
      myriads of disparate research reports and are replete with inconsistencies due to
      variations in experimental conditions and/or errors. It is often an intractable
      task to manually verify internal consistency over a large collection of
      experimental statements. To automate large-scale reconciliation efforts, we
      propose a random-arcs-and-nodes model where both nodes (tissue-specific states of
      biological molecules) and arcs (interactions between them) are represented with
      random variables. We show how to obtain a non-contradictory model of a molecular
      network by computing the joint distribution for arc and node variables, and then
      apply our methodology to a realistic network, generating a set of experimentally
      testable hypotheses. This network, derived from an automated analysis of over
      3,000 full-text research articles, includes genes that have been hypothetically
      linked to four neurological disorders: Alzheimer's disease, autism, bipolar
      disorder, and schizophrenia. We estimated that approximately 10% of the published
      molecular interactions are logically incompatible. Our approach can be directly
      applied to an array of diverse problems including those encountered in molecular
      biology, ecology, economics, politics, and sociology.

PMID- 17183694
TI  - Depauperate avifauna in plantations compared to forests and exurban areas.
AB  - Native forests are shrinking worldwide, causing a loss of biological diversity.
      Our ability to prioritize forest conservation actions is hampered by a lack of
      information about the relative impacts of different types of forest loss on
      biodiversity. In particular, we lack rigorous comparisons of the effects of
      clearing forests for tree plantations and for human settlements, two leading
      causes of deforestation worldwide. We compared avian diversity in forests,
      plantations and exurban areas on the Cumberland Plateau, USA, an area of global
      importance for biodiversity. By combining field surveys with digital habitat
      databases, and then analyzing diversity at multiple scales, we found that
      plantations had lower diversity and fewer conservation priority species than did
      other habitats. Exurban areas had higher diversity than did native forests, but
      native forests outscored exurban areas for some measures of conservation
      priority. Overall therefore, pine plantations had impoverished avian communities
      relative to both native forests and to exurban areas. Thus, reports on the status
      of forests give misleading signals about biological diversity when they include
      plantations in their estimates of forest cover but exclude forested areas in
      which humans live. Likewise, forest conservation programs should downgrade
      incentives for plantations and should include settled areas within their purview.

PMID- 17183695
TI  - Polymorphism in the MHC2TA gene is associated with features of the metabolic
      syndrome and cardiovascular mortality.
AB  - BACKGROUND: Recently, a -168A-->G polymorphism in the MHC class II transactivator
      gene (MHC2TA) was shown to be associated with increased susceptibility to
      myocardial infarction (MI). AIM: To confirm the association between the MHC2TA 
      168A-->G polymorphism and MI and to study its putative role for microalbuminuria,
      the metabolic syndrome (MetS) and cardiovascular mortality. MATERIALS AND
      METHODS: Using an allelic discrimination method we genotyped 11,064 individuals
      from three study populations: 1) 4,432 individuals from the Botnia type 2
      diabetes (T2D) study, 2) 1,222 patients with MI and 2,345 control subjects
      participating in the Malmo Diet and Cancer study and comprising an MI case
      control sample, and 3) 3,065 T2D patients from the Local Swedish Diabetes
      registry. RESULTS: No association between the -168A-->G polymorphism in MHC2TA
      and MI was observed. However, in the Botnia cohort the AG/GG genotypes were
      associated with cardiovascular mortality after MI (1.78 [1.09-2.92], p = 0.02).
      In addition, the AG/GG genotypes were more common in subjects with MetS (40.1%
      vs. 36.9%, p = 0.03) and in non-diabetic subjects with microalbuminuria (45.4%
      vs. 36.5%, p = 0.003) compared to control subjects. CONCLUSIONS: A polymorphism
      in MHC2TA was associated with cardiovascular mortality and predictors of
      cardiovascular mortality, microalbuminuria and MetS.

PMID- 17183696
TI  - Running speed in mammals increases with muscle n-6 polyunsaturated fatty acid
      content.
AB  - Polyunsaturated fatty acids (PUFAs) are important dietary components that mammals
      cannot synthesize de novo. Beneficial effects of PUFAs, in particular of the n-3
      class, for certain aspects of animal and human health (e.g., cardiovascular
      function) are well known. Several observations suggest, however, that PUFAs may
      also affect the performance of skeletal muscles in vertebrates. For instance, it
      has been shown that experimentally n-6 PUFA-enriched diets increase the maximum
      swimming speed in salmon. Also, we recently found that the proportion of PUFAs in
      the muscle phospholipids of an extremely fast runner, the brown hare (Lepus
      europaeus), are very high compared to other mammals. Therefore, we predicted that
      locomotor performance, namely running speed, should be associated with
      differences in muscle fatty acid profiles. To test this hypothesis, we determined
      phospholipid fatty acid profiles in skeletal muscles of 36 mammalian species
      ranging from shrews to elephants. We found that there is indeed a general
      positive, surprisingly strong relation between the n-6 PUFAs content in muscle
      phospholipids and maximum running speed of mammals. This finding suggests that
      muscle fatty acid composition directly affects a highly fitness-relevant trait,
      which may be decisive for the ability of animals to escape from predators or
      catch prey.

PMID- 17183697
TI  - The PDZ protein Canoe/AF-6 links Ras-MAPK, Notch and Wingless/Wnt signaling
      pathways by directly interacting with Ras, Notch and Dishevelled.
AB  - Over the past few years, it has become increasingly apparent that signal
      transduction pathways are not merely linear cascades; they are organized into
      complex signaling networks that require high levels of regulation to generate
      precise and unique cell responses. However, the underlying regulatory mechanisms
      by which signaling pathways cross-communicate remain poorly understood. Here we
      show that the Ras-binding protein Canoe (Cno)/AF-6, a PDZ protein normally
      associated with cellular junctions, is a key modulator of Wingless (Wg)/Wnt, Ras
      Mitogen Activated Protein Kinase (MAPK) and Notch (N) signaling pathways cross
      communication. Our data show a repressive effect of Cno/AF-6 on these three
      signaling pathways through physical interactions with Ras, N and the cytoplasmic
      protein Dishevelled (Dsh), a key Wg effector. We propose a model in which Cno,
      through those interactions, actively coordinates, at the membrane level, Ras
      MAPK, N and Wg signaling pathways during progenitor specification.

PMID- 17183698
TI  - 'Fractional recovery' analysis of a presynaptic synaptotagmin 1-anchored
      endocytic protein complex.
AB  - BACKGROUND: The integral synaptic vesicle protein and putative calcium sensor,
      synaptotagmin 1 (STG), has also been implicated in synaptic vesicle (SV)
      recovery. However, proteins with which STG interacts during SV endocytosis remain
      poorly understood. We have isolated an STG-associated endocytic complex (SAE)
      from presynaptic nerve terminals and have used a novel fractional recovery (FR)
      assay based on electrostatic dissociation to identify SAE components and map the
      complex structure. The location of SAE in the presynaptic terminal was determined
      by high-resolution quantitative immunocytochemistry at the chick ciliary ganglion
      giant calyx-type synapse. METHODOLOGY/PRINCIPLE FINDINGS: The first step in FR
      analysis was to immunoprecipitate (IP) the complex with an antibody against one
      protein component (the IP-protein). The immobilized complex was then exposed to a
      high salt (1150 mM) stress-test that caused shedding of co-immunoprecipitated
      proteins (co-IP-proteins). A Fractional Recovery ratio (FR: recovery after high
      salt/recovery with control salt as assayed by Western blot) was calculated for
      each co-IP-protein. These FR values reflect complex structure since an easily
      dissociated protein, with a low FR value, cannot be intermediary between the IP
      protein and a salt-resistant protein. The structure of the complex was mapped and
      a blueprint generated with a pair of FR analyses generated using two different IP
      proteins. The blueprint of SAE contains an AP180/X/STG/stonin 2/intersectin/epsin
      core (X is unknown and epsin is hypothesized), and an AP2 adaptor, H-/L-clathrin
      coat and dynamin scission protein perimeter. Quantitative immunocytochemistry
      (ICA/ICQ method) at an isolated calyx-type presynaptic terminal indicates that
      this complex is associated with STG at the presynaptic transmitter release face
      but not with STG on intracellular synaptic vesicles. CONCLUSIONS/SIGNIFICANCE: We
      hypothesize that the SAE serves as a recognition site and also as a seed complex
      for clathrin-mediated synaptic vesicle recovery. The combination of FR analysis
      with quantitative immunocytochemistry provides a novel and effective strategy for
      the identification and characterization of biologically-relevant multi-molecular
      complexes.

PMID- 17183699
TI  - Surprisingly high specificity of the PPD skin test for M. tuberculosis infection
      from recent exposure in The Gambia.
AB  - BACKGROUND: Options for intervention against Mycobacterium tuberculosis infection
      are limited by the diagnostic tools available. The Purified Protein Derivative
      (PPD) skin test is thought to be non-specific, especially in tropical settings.
      We compared the PPD skin test with an ELISPOT test in The Gambia.
      METHODOLOGY/PRINCIPAL FINDINGS: Household contacts over six months of age of
      sputum smear positive TB cases and community controls were recruited. They
      underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and
      ESAT-6/CFP10 antigens. Responsiveness to M. tuberculosis exposure was analysed
      according to sleeping proximity to an index case using logistic regression. 615
      household contacts and 105 community controls were recruited. All three tests
      assessed increased significantly in positivity with increasing M. tuberculosis
      exposure, the PPD skin test most dramatically (OR 15.7; 95% CI 6.6-35.3). While
      the PPD skin test positivity continued to trend downwards in the community with
      increasing distance from a known case (61.9% to 14.3%), the PPD and ESAT-6/CFP-10
      ELISPOT positivity did not. The PPD skin test was more in agreement with ESAT
      6/CFP-10 ELISPOT (75%, p = 0.01) than the PPD ELISPOT (53%, p<0.0001). With
      increasing M. tuberculosis exposure, the proportion of ESAT-6/CFP-10 positive
      contacts who were PPD skin test positive increased (p<0.0001), and the proportion
      of ESAT-6/CFP-10 negative contacts that were PPD skin test negative decreased
      (p<0.0001); the converse did not occur. CONCLUSIONS/SIGNIFICANCE: The PPD skin
      test has surprisingly high specificity for M. tuberculosis infection from recent
      exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin
      test positive individuals should be revisited.

PMID- 17183700
TI  - Neurovirulent vaccine-derived polioviruses in sewage from highly immune
      populations.
AB  - BACKGROUND: Vaccine-derived polioviruses (VDPVs) have caused poliomyelitis
      outbreaks in communities with sub-optimal vaccination. Israeli environmental
      surveillance of sewage from populations with high (>95%) documented vaccine
      coverage of confirmed efficacy identified two separate evolutionary clusters of
      VDPVs: Group 1 (1998-2005, one system, population 1.6x10(6)) and Group 2 (2006, 2
      systems, populations 0.7x10(6) and 5x10(4)). PRINCIPAL FINDINGS: Molecular
      analyses support evolution of nine Group 1 VDPVs along five different lineages,
      starting from a common ancestral type 2 vaccine-derived Sabin-2/Sabin-1
      recombinant strain, and independent evolution of three Group 2 VDPVs along one
      lineage starting from a different recombinant strain. The primary evidence for
      two independent origins was based on comparison of unique recombination
      fingerprints, the number and distribution of identical substitutions, and
      evolutionary rates. Geometric mean titers of neutralizing antibodies against
      Group 1 VDPVs were significantly lower than against vaccine strains in all age
      group cohorts tested. All individuals had neutralizing titers >1:8 against these
      VDPVs except 7% of the 20-50 year cohort. Group 1 VDPVs were highly neurovirulent
      in a transgenic mouse model. Intermediate levels of protective immunity against
      Group 2 VDPVs correlated with fewer (5.0+1.0) amino acid substitutions in
      neutralizing antigenic sites than in Group 1 VDPV's (12.1+/-1.5). SIGNIFICANCE:
      VDPVs that revert from live oral attenuated vaccines and reacquire
      characteristics of wild-type polioviruses not only threaten populations with poor
      immune coverage, but are also a potential source for re-introduction of
      poliomyelitis into highly immune populations through older individuals with
      waning immunity. The presence of two independently evolved groups of VDPVs in
      Israel and the growing number of reports of environmental VDPV elsewhere make it
      imperative to determine the global frequency of environmental VDPV. Our study
      underscores the importance of the environmental surveillance and the need to
      reconsider the global strategies for polio eradication and the proposed cessation
      of vaccination.

PMID- 17183701
TI  - A single basis for developmental buffering of Drosophila wing shape.
AB  - The nature of developmental buffering processes has been debated extensively,
      based on both theoretical reasoning and empirical studies. In particular,
      controversy has focused on the question of whether distinct processes are
      responsible for canalization, the buffering against environmental or genetic
      variation, and for developmental stability, the buffering against random
      variation intrinsic in developmental processes. Here, we address this question
      for the size and shape of Drosophila melanogaster wings in an experimental design
      with extensively replicated and fully controlled genotypes. The amounts of
      variation among individuals and of fluctuating asymmetry differ markedly among
      genotypes, demonstrating a clear genetic basis for size and shape variability.
      For wing shape, there is a high correlation between the amounts of variation
      among individuals and fluctuating asymmetry, which indicates a correspondence
      between the two types of buffering. Likewise, the multivariate patterns of shape
      variation among individuals and of fluctuating asymmetry show a close
      association. For wing size, however, the amounts of individual variation and
      fluctuating asymmetry are not correlated. There was a significant link between
      the amounts of variation between wing size and shape, more so for fluctuating
      asymmetry than for variation among individuals. Overall, these experiments
      indicate a considerable degree of shared control of individual variation and
      fluctuating asymmetry, although it appears to differ between traits.

PMID- 17183702
TI  - Catalases are NAD(P)H-dependent tellurite reductases.
AB  - Reactive oxygen species damage intracellular targets and are implicated in
      cancer, genetic disease, mutagenesis, and aging. Catalases are among the key
      enzymatic defenses against one of the most physiologically abundant reactive
      oxygen species, hydrogen peroxide. The well-studied, heme-dependent catalases
      accelerate the rate of the dismutation of peroxide to molecular oxygen and water
      with near kinetic perfection. Many catalases also bind the cofactors NADPH and
      NADH tenaciously, but, surprisingly, NAD(P)H is not required for their dismutase
      activity. Although NAD(P)H protects bovine catalase against oxidative damage by
      its peroxide substrate, the catalytic role of the nicotinamide cofactor in the
      function of this enzyme has remained a biochemical mystery to date. Anions formed
      by heavy metal oxides are among the most highly reactive, natural oxidizing
      agents. Here, we show that a natural isolate of Staphylococcus epidermidis
      resistant to tellurite detoxifies this anion thanks to a novel activity of its
      catalase, and that a subset of both bacterial and mammalian catalases carry out
      the NAD(P)H-dependent reduction of soluble tellurite ion (TeO(3)(2-)) to the less
      toxic, insoluble metal, tellurium (Te(o)), in vitro. An Escherichia coli mutant
      defective in the KatG catalase/peroxidase is sensitive to tellurite, and
      expression of the S. epidermidis catalase gene in a heterologous E. coli host
      confers increased resistance to tellurite as well as to hydrogen peroxide in
      vivo, arguing that S. epidermidis catalase provides a physiological line of
      defense against both of these strong oxidizing agents. Kinetic studies reveal
      that bovine catalase reduces tellurite with a low Michaelis-Menten constant, a
      result suggesting that tellurite is among the natural substrates of this enzyme.
      The reduction of tellurite by bovine catalase occurs at the expense of producing
      the highly reactive superoxide radical.

PMID- 17183703
TI  - Prion protein in milk.
AB  - BACKGROUND: Prions are known to cause transmissible spongiform encephalopathies
      (TSE) after accumulation in the central nervous system. There is increasing
      evidence that prions are also present in body fluids and that prion infection by
      blood transmission is possible. The low concentration of the proteinaceous agent
      in body fluids and its long incubation time complicate epidemiologic analysis and
      estimation of spreading and thus the risk of human infection. This situation is
      particularly unsatisfactory for food and pharmaceutical industries, given the
      lack of sensitive tools for monitoring the infectious agent.
      METHODOLOGY/PRINCIPAL FINDINGS: We have developed an adsorption matrix, Alicon
      PrioTrap, which binds with high affinity and specificity to prion proteins. Thus
      we were able to identify prion protein (PrP(C))--the precursor of prions
      (PrP(Sc))--in milk from humans, cows, sheep, and goats. The absolute amount of
      PrP(C) differs between the species (from microg/l range in sheep to ng/l range in
      human milk). PrP(C) is also found in homogenised and pasteurised off-the-shelf
      milk, and even ultrahigh temperature treatment only partially diminishes
      endogenous PrP(C) concentration. CONCLUSIONS/SIGNIFICANCE: In view of a recent
      study showing evidence of prion replication occurring in the mammary gland of
      scrapie infected sheep suffering from mastitis, the appearance of PrP(C) in milk
      implies the possibility that milk of TSE-infected animals serves as source for
      PrP(Sc).

PMID- 17183704
TI  - Selection for heterozygosity gives hope to a wild population of inbred wolves.
AB  - Recent analyses have questioned the usefulness of heterozygosity estimates as
      measures of the inbreeding coefficient (f), a finding that may have dramatic
      consequences for the management of endangered populations. We confirm that f and
      heterozygosity is poorly correlated in a wild and highly inbred wolf population.
      Yet, our data show that for each level of f, it was the most heterozygous wolves
      that established themselves as breeders, a selection process that seems to have
      decelerated the loss of heterozygosity in the population despite a steady
      increase of f. The markers contributing to the positive relationship between
      heterozygosity and breeding success were found to be located on different
      chromosomes, but there was a substantial amount of linkage disequilibrium in the
      population, indicating that the markers are reflecting heterozygosity over
      relatively wide genomic regions. Following our results we recommend that
      management programs of endangered populations include estimates of both f and
      heterozygosity, as they may contribute with complementary information about
      population viability.

PMID- 17183705
TI  - The syntax and meaning of wild gibbon songs.
AB  - Spoken language is a result of the human capacity to assemble simple vocal units
      into more complex utterances, the basic carriers of semantic information. Not
      much is known about the evolutionary origins of this behaviour. The vocal
      abilities of non-human primates are relatively unimpressive in comparison, with
      gibbon songs being a rare exception. These apes assemble a repertoire of call
      notes into elaborate songs, which function to repel conspecific intruders,
      advertise pair bonds, and attract mates. We conducted a series of field
      experiments with white-handed gibbons at Khao Yai National Park, Thailand, which
      showed that this ape species uses songs also to protect themselves against
      predation. We compared the acoustic structure of predatory-induced songs with
      regular songs that were given as part of their daily routine. Predator-induced
      songs were identical to normal songs in the call note repertoire, but we found
      consistent differences in how the notes were assembled into songs. The responses
      of out-of-sight receivers demonstrated that these syntactic differences were
      meaningful to conspecifics. Our study provides the first evidence of referential
      signalling in a free-ranging ape species, based on a communication system that
      utilises combinatorial rules.

PMID- 17183706
TI  - Late Cretaceous vicariance in Gondwanan amphibians.
AB  - Overseas dispersals are often invoked when Southern Hemisphere terrestrial and
      freshwater organism phylogenies do not fit the sequence or timing of Gondwana
      fragmentation. We used dispersal-vicariance analyses and molecular timetrees to
      show that two species-rich frog groups, Microhylidae and Natatanura, display
      congruent patterns of spatial and temporal diversification among Gondwanan plates
      in the Late Cretaceous, long after the presumed major tectonic break-up events.
      Because amphibians are notoriously salt-intolerant, these analogies are best
      explained by simultaneous vicariance, rather than by oceanic dispersal. Hence our
      results imply Late Cretaceous connections between most adjacent Gondwanan
      landmasses, an essential concept for biogeographic and palaeomap reconstructions.

PMID- 17183707
TI  - Control of canalization and evolvability by Hsp90.
AB  - Partial reduction of Hsp90 increases expression of morphological novelty in
      qualitative traits of Drosophila and Arabidopsis, but the extent to which the
      Hsp90 chaperone also controls smaller and more likely adaptive changes in natural
      quantitative traits has been unclear. To determine the effect of Hsp90 on
      quantitative trait variability we deconstructed genetic, stochastic and
      environmental components of variation in Drosophila wing and bristle traits of
      genetically matched flies, differing only by Hsp90 loss-of-function or wild-type
      alleles. Unexpectedly, Hsp90 buffering was remarkably specific to certain
      normally invariant and highly discrete quantitative traits. Like the qualitative
      trait phenotypes controlled by Hsp90, highly discrete quantitative traits such as
      scutellor and thoracic bristle number are threshold traits. When tested across
      genotypes sampled from a wild population or in laboratory strains, the
      sensitivity of these traits to many types of variation was coordinately
      controlled, while continuously variable bristle types and wing size, and
      critically invariant left-right wing asymmetry, remained relatively unaffected.
      Although increased environmental variation and developmental noise would impede
      many types of selection response, in replicate populations in which Hsp90 was
      specifically impaired, heritability and 'extrinsic evolvability', the expected
      response to selection, were also markedly increased. However, despite the overall
      buffering effect of Hsp90 on variation in populations, for any particular
      individual or genotype in which Hsp90 was impaired, the size and direction of its
      effects were unpredictable. The trait and genetic-background dependence of Hsp90
      effects and its remarkable bias toward invariant or canalized traits support the
      idea that traits evolve independent and trait-specific mechanisms of canalization
      and evolvability through their evolution of non-linearity and thresholds. Highly
      non-linear responses would buffer variation in Hsp90-dependent signaling over a
      wide range, while over a narrow range of signaling near trait thresholds become
      more variable with increasing probability of triggering all-or-none developmental
      responses.

PMID- 17183708
TI  - Modularity and intrinsic evolvability of Hsp90-buffered change.
AB  - Hsp90 controls dramatic phenotypic transitions in a wide array of morphological
      features of many organisms. The genetic-background dependence of specific
      abnormalities and their response to laboratory selection suggested Hsp90 could be
      an 'evolutionary capacitor', allowing developmental variation to accumulate as
      neutral alleles under normal conditions and manifest selectable morphological
      differences during environmental stress. The relevance of Hsp90-buffered
      variation for evolution has been most often challenged by the idea that large
      morphological changes controlled by Hsp90 are unconditionally deleterious. To
      address this issue, we tested an Hsp90-buffered abnormality in Drosophila for
      unselected pleiotropic effects and correlated fitness costs. Up to 120-fold
      differences in penetrance among six highly related selection lines, started from
      an initially small number of flies and rapidly selected for and against a
      deformed eye trait (dfe), did not translate into measurable differences in any of
      several tests of viability, lifespan or competitive fitness. Nor were 17 dfe
      Quantitative Trait Loci (QTL) associated with fitness effects in over 1,400
      recombinant lines. Our ability to detect measurable effects of inbreeding, media
      environment and the white mutation in the selection line backgrounds independent
      of dfe penetrance suggests that, within the limitations of laboratory tests of
      fitness, this large morphological change controlled by Hsp90 was selectable
      independent of strong, correlated and unconditionally deleterious effects-
      abundant, polygenic variation hidden by Hsp90 allows potentially deleterious
      alleles to be readily replaced during selection by less deleterious alleles with
      similar phenotypic effects. Hsp90 links environmental stress with the expression
      of developmental variation controlling unprecedented morphological plasticity. As
      outlined here and in the companion paper of this issue, the complex genetic
      architecture of Hsp90-buffered variation supports a remarkable modularity of
      Hsp90 effects on quantitative and qualitative phenotypes, consistent with the
      'Hsp90 capacitor hypothesis' and standard quantitative genetic models of
      threshold traits.

PMID- 17183709
TI  - GATA transcription factor required for immunity to bacterial and fungal
      pathogens.
AB  - In the past decade, Caenorhabditis elegans has been used to dissect several
      genetic pathways involved in immunity; however, little is known about
      transcription factors that regulate the expression of immune effectors. C.
      elegans does not appear to have a functional homolog of the key immune
      transcription factor NF-kappaB. Here we show that that the intestinal GATA
      transcription factor ELT-2 is required for both immunity to Salmonella enterica
      and expression of a C-type lectin gene, clec-67, which is expressed in the
      intestinal cells and is a good marker of S. enterica infection. We also found
      that ELT-2 is required for immunity to Pseudomonas aeruginosa, Enterococcus
      faecalis, and Cryptococcus neoformans. Lack of immune inhibition by DAF-2, which
      negatively regulates the FOXO transcription factor DAF-16, rescues the
      hypersusceptibility to pathogens phenotype of elt-2(RNAi) animals. Our results
      indicate that ELT-2 is part of a multi-pathogen defense pathway that regulates
      innate immunity independently of the DAF-2/DAF-16 signaling pathway.

PMID- 17183710
TI  - Non-neutral vegetation dynamics.
AB  - The neutral theory of biodiversity constitutes a reference null hypothesis for
      the interpretation of ecosystem dynamics and produces relatively simple
      analytical descriptions of basic system properties, which can be easily compared
      to observations. On the contrary, investigations in non-neutral dynamics have in
      the past been limited by the complexity arising from heterogeneous demographic
      behaviours and by the relative paucity of detailed observations of the spatial
      distribution of species diversity (beta-diversity): These circumstances prevented
      the development and testing of explicit non-neutral mathematical descriptions
      linking competitive strategies and observable ecosystem properties. Here we
      introduce an exact non-neutral model of vegetation dynamics, based on cloning and
      seed dispersal, which yields closed-form characterizations of beta-diversity. The
      predictions of the non-neutral model are validated using new high-resolution
      remote-sensing observations of salt-marsh vegetation in the Venice Lagoon
      (Italy). Model expressions of beta-diversity show a remarkable agreement with
      observed distributions within the wide observational range of scales explored (5
      x 10(-1) m divided by 10(3) m). We also consider a neutral version of the model
      and find its predictions to be in agreement with the more limited
      characterization of beta-diversity typical of the neutral theory (based on the
      likelihood that two sites be conspecific or heterospecific, irrespective of the
      species). However, such an agreement proves to be misleading as the recruitment
      rates by propagules and by seed dispersal assumed by the neutral model do not
      reflect known species characteristics and correspond to averages of those
      obtained under the more general non-neutral hypothesis. We conclude that non
      neutral beta-diversity characterizations are required to describe ecosystem
      dynamics in the presence of species-dependent properties and to successfully
      relate the observed patterns to the underlying processes.

PMID- 17183711
TI  - Mesenchymal stem cell-mediated functional tooth regeneration in swine.
AB  - Mesenchymal stem cell-mediated tissue regeneration is a promising approach for
      regenerative medicine for a wide range of applications. Here we report a new
      population of stem cells isolated from the root apical papilla of human teeth
      (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted
      both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a
      root/periodontal complex capable of supporting a porcelain crown, resulting in
      normal tooth function. This work integrates a stem cell-mediated tissue
      regeneration strategy, engineered materials for structure, and current dental
      crown technologies. This hybridized tissue engineering approach led to recovery
      of tooth strength and appearance.

PMID- 17183712
TI  - Molecular adaptation during adaptive radiation in the Hawaiian endemic genus
      Schiedea.
AB  - BACKGROUND: "Explosive" adaptive radiations on islands remain one of the most
      puzzling evolutionary phenomena. The rate of phenotypic and ecological
      adaptations is extremely fast during such events, suggesting that many genes may
      be under fairly strong selection. However, no evidence for adaptation at the
      level of protein coding genes was found, so it has been suggested that selection
      may work mainly on regulatory elements. Here we report the first evidence that
      positive selection does operate at the level of protein coding genes during rapid
      adaptive radiations. We studied molecular adaptation in Hawaiian endemic plant
      genus Schiedea (Caryophyllaceae), which includes closely related species with a
      striking range of morphological and ecological forms, varying from rainforest
      vines to woody shrubs growing in desert-like conditions on cliffs. Given the
      remarkable difference in photosynthetic performance between Schiedea species from
      different habitats, we focused on the "photosynthetic" Rubisco enzyme, the
      efficiency of which is known to be a limiting step in plant photosynthesis.
      RESULTS: We demonstrate that the chloroplast rbcL gene, encoding the large
      subunit of Rubisco enzyme, evolved under strong positive selection in Schiedea.
      Adaptive amino acid changes occurred in functionally important regions of Rubisco
      that interact with Rubisco activase, a chaperone which promotes and maintains the
      catalytic activity of Rubisco. Interestingly, positive selection acting on the
      rbcL might have caused favorable cytotypes to spread across several Schiedea
      species. SIGNIFICANCE: We report the first evidence for adaptive changes at the
      DNA and protein sequence level that may have been associated with the evolution
      of photosynthetic performance and colonization of new habitats during a recent
      adaptive radiation in an island plant genus. This illustrates how small changes
      at the molecular level may change ecological species performance and helps us to
      understand the molecular bases of extremely fast rate of adaptation during island
      adaptive radiations.

PMID- 17183713
TI  - Cross species association examination of UCN3 and CRHR2 as potential
      pharmacological targets for antiobesity drugs.
AB  - BACKGROUND: Obesity now constitutes a leading global public health problem.
      Studies have shown that insulin resistance affiliated with obesity is associated
      with intramyocellular lipid (IMCL) accumulation. Therefore, identification of
      genes associated with the phenotype would provide a clear target for
      pharmaceutical intervention and care for the condition. We hypothesized that
      urocortin 3 (UCN3) and corticotropin-releasing hormone receptor 2 (CRHR2) are
      associated with IMCL and subcutaneous fat depth (SFD), because the corticotropin
      releasing hormone family of peptides are capable of strong anorectic and
      thermogenic effects. METHODOLOGY/PRINCIPAL FINDINGS: We annotated both bovine
      UCN3 and CRHR2 genes and identified 12 genetic mutations in the former gene and 5
      genetic markers in the promoter region of the latter gene. Genotyping of these 17
      markers on Wagyu times Limousin F(2) progeny revealed significant associations
      between promoter polymorphisms and SFD (P = 0.0203-0.0685) and between missense
      mutations of exon 2 and IMCL (P = 0.0055-0.0369) in the bovine UCN3 gene. The SFD
      associated promoter SNPs caused a gain/loss of 12 potential transcription
      regulatory binding sites, while the IMCL associated coding SNPs affected the
      secondary structure of UCN3 mRNA. However, none of five polymorphisms in CRHR2
      gene clearly co-segregated with either trait in the population (P>0.6000).
      CONCLUSIONS/SIGNIFICANCE: Because UCN3 is located on human chromosome 10p15.1
      where quantitative trait loci for obesity have been reported, our cross species
      study provides further evidence that it could be proposed as a potential target
      for developing antiobesity drugs. None of the markers in CRHR2 was associated
      with obesity-type traits in cattle, which is consistent with findings in human.
      Therefore, CRHR2 does not lend itself to the development of antiobesity drugs.

PMID- 17183714
TI  - Separation of anti-proliferation and anti-apoptotic functions of retinoblastoma
      protein through targeted mutations of its A/B domain.
AB  - BACKGROUND: The human retinoblastoma susceptibility gene encodes a nuclear
      phosphoprotein RB, which is a negative regulator of cell proliferation. The
      growth suppression function of RB requires an evolutionarily conserved A/B domain
      that contains two distinct peptide-binding pockets. At the A/B interface is a
      binding site for the C-terminal trans-activation domain of E2F. Within the B
      domain is a binding site for proteins containing the LxCxE peptide motif.
      METHODOLOGY/PRINCIPLE FINDINGS: Based on the crystal structure of the A/B domain,
      we have constructed an RB-K530A/N757F (KN) mutant to disrupt the E2F- and LxCxE
      binding pockets. The RB-K530A (K) mutant is sufficient to inactivate the E2F
      binding pocket, whereas the RB-N757F (N) mutant is sufficient to inactivate the
      LxCxE-binding pocket. Each single mutant inhibits cell proliferation, but the RB
      KN double mutant is defective in growth suppression. Nevertheless, the RB-KN
      mutant is capable of reducing etoposide-induced apoptosis.
      CONCLUSION/SIGNIFICANCE: Previous studies have established that RB-dependent G1
      arrest can confer resistance to DNA damage-induced apoptosis. Results from this
      study demonstrate that RB can also inhibit apoptosis independent of growth
      suppression.

PMID- 17183715
TI  - Hyperhomocysteinemia and mortality after coronary artery bypass grafting.
AB  - BACKGROUND: The independent prognostic impact, as well as the possible causal
      role, of hyperhomocysteinemia (HHcy) in coronary artery disease (CAD) is
      controversial. No previous study specifically has addressed the relationship
      between HHcy and mortality after coronary artery bypass grafting (CABG) surgery.
      The aim of this study is to evaluate the prognostic impact of HHcy after CABG
      surgery. METHODOLOGY AND PRINCIPAL FINDINGS: We prospectively followed 350
      patients who underwent elective CABG between May 1996 and May 1999. At baseline,
      fasting total homocysteine (tHcy) levels were measured in all participants, and a
      post-methionine loading (PML) test was performed in 77.7% of them (n = 272).
      After a median follow-up of 58 months, 33 patients (9.4%) had died, 25 because of
      cardiovascular events. HHcy, defined by levels higher than the 90th percentile
      (25.2 micromol/L) of the population's distribution, was significantly associated
      to total and cardiovascular mortality (P = 0.018 [log-rank test 5.57]; P = 0.002
      [log-rank test 9.76], respectively). The PML test had no prognostic value. After
      multiple adjustment for other univariate predictors by Cox regression, including
      statin therapy (the most powerful predictor in uni-/multivariate analyses), high
      sensitivity C Reactive Protein (hs-CRP) levels, and all known major genetic
      (MTHFR 677C-->T polymorphism) and non-genetic (B-group vitamin status and renal
      function) tHcy determinants, HHcy remained an independent prognostic factor for
      mortality (HRs: 5.02, 95% CIs 1.88 to 13.42, P = 0.001). CONCLUSIONS: HHcy is an
      important prognostic marker after CABG, independent of modern drug therapy and
      biomarkers.

PMID- 17183716
TI  - The evolution of mammalian gene families.
AB  - Gene families are groups of homologous genes that are likely to have highly
      similar functions. Differences in family size due to lineage-specific gene
      duplication and gene loss may provide clues to the evolutionary forces that have
      shaped mammalian genomes. Here we analyze the gene families contained within the
      whole genomes of human, chimpanzee, mouse, rat, and dog. In total we find that
      more than half of the 9,990 families present in the mammalian common ancestor
      have either expanded or contracted along at least one lineage. Additionally, we
      find that a large number of families are completely lost from one or more
      mammalian genomes, and a similar number of gene families have arisen subsequent
      to the mammalian common ancestor. Along the lineage leading to modern humans we
      infer the gain of 689 genes and the loss of 86 genes since the split from
      chimpanzees, including changes likely driven by adaptive natural selection. Our
      results imply that humans and chimpanzees differ by at least 6% (1,418 of 22,000
      genes) in their complement of genes, which stands in stark contrast to the oft
      cited 1.5% difference between orthologous nucleotide sequences. This genomic
      "revolving door" of gene gain and loss represents a large number of genetic
      differences separating humans from our closest relatives.

PMID- 17183717
TI  - Error processing in Huntington's disease.
AB  - BACKGROUND: Huntington's disease (HD) is a genetic disorder expressed by a
      degeneration of the basal ganglia inter alia accompanied with dopaminergic
      alterations. These dopaminergic alterations are related to genetic factors i.e.,
      CAG-repeat expansion. The error (related) negativity (Ne/ERN), a cognitive event
      related potential related to performance monitoring, is generated in the anterior
      cingulate cortex (ACC) and supposed to depend on the dopaminergic system. The Ne
      is reduced in Parkinson's Disease (PD). Due to a dopaminergic deficit in HD, a
      reduction of the Ne is also likely. Furthermore it is assumed that movement
      dysfunction emerges as a consequence of dysfunctional error-feedback processing.
      Since dopaminergic alterations are related to the CAG-repeat, a Ne reduction may
      furthermore also be related to the genetic disease load. METHODOLOGY/PRINCIPLE
      FINDINGS: We assessed the error negativity (Ne) in a speeded reaction task under
      consideration of the underlying genetic abnormalities. HD patients showed a
      specific reduction in the Ne, which suggests impaired error processing in these
      patients. Furthermore, the Ne was closely related to CAG-repeat expansion.
      CONCLUSIONS/SIGNIFICANCE: The reduction of the Ne is likely to be an effect of
      the dopaminergic pathology. The result resembles findings in Parkinson's Disease.
      As such the Ne might be a measure for the integrity of striatal dopaminergic
      output function. The relation to the CAG-repeat expansion indicates that the Ne
      could serve as a gene-associated "cognitive" biomarker in HD.

PMID- 17183718
TI  - Modulation of T cell function by combination of epitope specific and low dose
      anticytokine therapy controls autoimmune arthritis.
AB  - Innate and adaptive immunity contribute to the pathogenesis of autoimmune
      arthritis by generating and maintaining inflammation, which leads to tissue
      damage. Current biological therapies target innate immunity, eminently by
      interfering with single pro-inflammatory cytokine pathways. This approach has
      shown excellent efficacy in a good proportion of patients with Rheumatoid
      Arthritis (RA), but is limited by cost and side effects. Adaptive immunity,
      particularly T cells with a regulatory function, plays a fundamental role in
      controlling inflammation in physiologic conditions. A growing body of evidence
      suggests that modulation of T cell function is impaired in autoimmunity.
      Restoration of such function could be of significant therapeutic value. We have
      recently demonstrated that epitope-specific therapy can restore modulation of T
      cell function in RA patients. Here, we tested the hypothesis that a combination
      of anti-cytokine and epitope-specific immunotherapy may facilitate the control of
      autoimmune inflammation by generating active T cell regulation. This novel
      combination of mucosal tolerization to a pathogenic T cell epitope and single low
      dose anti-TNFalpha was as therapeutically effective as full dose anti-TNFalpha
      treatment. Analysis of the underlying immunological mechanisms showed induction
      of T cell immune deviation.

PMID- 17183719
TI  - Probe selection and expression index computation of Affymetrix Exon Arrays.
AB  - BACKGROUND: There is great current interest in developing microarray platforms
      for measuring mRNA abundance at both gene level and exon level. The Affymetrix
      Exon Array is a new high-density gene expression microarray platform, with over
      six million probes targeting all annotated and predicted exons in a genome. An
      important question for the analysis of exon array data is how to compute overall
      gene expression indexes. Because of the complexity of the design of exon array
      probes, this problem is different in nature from summarizing gene-level
      expression from traditional 3' expression arrays. METHODOLOGY/PRINCIPAL FINDINGS:
      In this manuscript, we use exon array data from 11 human tissues to study methods
      for computing gene-level expression. We showed that for most genes there is a
      subset of exon array probes having highly correlated intensities across multiple
      samples. We suggest that these probes could be used as reliable indicators of
      overall gene expression levels. We developed a probe selection algorithm to
      select such a subset of highly correlated probes for each gene, and computed gene
      expression indexes using the selected probes. CONCLUSIONS/SIGNIFICANCE: Our
      results demonstrate that probe selection improves gene expression estimates from
      exon arrays. The selected probes can be used in future analyses of other exon
      array datasets to compute gene expression indexes.

PMID- 17183720
TI  - Clinical outcome of HIV-infected patients with sustained virologic response to
      antiretroviral therapy: long-term follow-up of a multicenter cohort.
AB  - BACKGROUND: Limited information exists on long-term prognosis of patients with
      sustained virologic response to antiretroviral therapy. We aimed to assess
      predictors of unfavorable clinical outcome in patients who maintain viral
      suppression with HAART. METHODS: Using data collected from ten clinic-based
      cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART
      and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up.
      Factors associated with disease progression were determined by Cox proportional
      hazards models. RESULTS: Of 2,613 patients who started HAART, 757 fulfilled the
      inclusion criteria. 61% of them initiated a protease inhibitor-based HAART
      regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and
      7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22
      (2.9%) patients died (mortality rate 0.86 per 100 person-years), and 40 (5.3%)
      died or developed a new AIDS-defining event. The most common causes of death were
      neoplasias and liver failure. Mortality was independently associated with a CD4-T
      cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR],
      4.26 [95% confidence interval {CI}, 1.68-10.83]; P = .002), and age at initiation
      of HAART (AHR, 1.06 per year; 95% CI, 1.02-1.09; P = .001). Initial
      antiretroviral regimen chosen was not associated with different risk of clinical
      progression. CONCLUSIONS: Patients with sustained virologic response on HAART
      have a low mortality rate over time. Long-term outcome of these patients is
      driven by immunologic response at the end of the first year of therapy and age at
      the time of HAART initiation, but not by the initial antiretroviral regimen
      selected.

PMID- 17183721
TI  - Wnt, Hedgehog and junctional Armadillo/beta-catenin establish planar polarity in
      the Drosophila embryo.
AB  - To generate specialized structures, cells must obtain positional and directional
      information. In multi-cellular organisms, cells use the non-canonical Wnt or
      planar cell polarity (PCP) signaling pathway to establish directionality within a
      cell. In vertebrates, several Wnt molecules have been proposed as permissible
      polarity signals, but none has been shown to provide a directional cue. While PCP
      signaling components are conserved from human to fly, no PCP ligands have been
      reported in Drosophila. Here we report that in the epidermis of the Drosophila
      embryo two signaling molecules, Hedgehog (Hh) and Wingless (Wg or Wnt1), provide
      directional cues that induce the proper orientation of Actin-rich structures in
      the larval cuticle. We further find that proper polarity in the late embryo also
      involves the asymmetric distribution and phosphorylation of Armadillo (Arm or
      beta-catenin) at the membrane and that interference with this Arm phosphorylation
      leads to polarity defects. Our results suggest new roles for Hh and Wg as
      instructive polarizing cues that help establish directionality within a cell
      sheet, and a new polarity-signaling role for the membrane fraction of the
      oncoprotein Arm.

PMID- 17183722
TI  - Age-related attenuation of dominant hand superiority.
AB  - BACKGROUND: The decline of motor performance of the human hand-arm system with
      age is well-documented. While dominant hand performance is superior to that of
      the non-dominant hand in young individuals, little is known of possible age
      related changes in hand dominance. We investigated age-related alterations of
      hand dominance in 20 to 90 year old subjects. All subjects were unambiguously
      right-handed according to the Edinburgh Handedness Inventory. In Experiment 1,
      motor performance for aiming, postural tremor, precision of arm-hand movement,
      speed of arm-hand movement, and wrist-finger speed tasks were tested. In
      Experiment 2, accelerometer-sensors were used to obtain objective records of hand
      use in everyday activities. PRINCIPAL FINDINGS: Our data confirm previous
      findings of a general task-dependent decline in motor performance with age.
      Analysis of the relationship between right/left-hand performances using a
      laterality index showed a loss of right hand dominance with advancing age. The
      clear right-hand advantage present at younger ages changed to a more balanced
      performance in advanced age. This shift was due to a more pronounced age-related
      decline of right hand performance. Accelerometer-sensor measurements supported
      these findings by demonstrating that the frequency of hand use also shifted from
      a clear right hand preference in young adults to a more balanced usage of both
      hands in old age. Despite these age-related changes in the relative level of
      performance in defined motor tasks and in the frequency of hand use, elderly
      subjects continued to rate themselves as unambiguous right-handers. CONCLUSION:
      The discrepancy between hand-specific practical performance in controlled motor
      tests as well as under everyday conditions and the results of questionnaires
      concerning hand use and hand dominance suggests that most elderly subjects are
      unaware of the changes in hand dominance that occur over their lifespan, i.e., a
      shift to ambidexterity.

PMID- 17183723
TI  - Human coronary artery remodeling, beginning and end of the atherosclerotic
      process.
AB  - BACKGROUND, AIMS OF THE STUDY: The objective of the study was to relate the
      progress of coronary artery remodeling to the earliest stages of the
      atherosclerotic process. For this purpose, a mathematical model for description
      of dimensional change of the coronary artery wall and its constituent components
      was developed and applied. MATERIALS AND METHODS: The study used coronary artery
      samples randomly taken from each of 83 consecutive, unselected postmortems. All
      samples were routinely fixed and processed to paraffin for the preparation of
      right-angled, 5-micron sections, routinely stained and mounted for subsequent
      analysis. Computer assisted image analysis, using 32 systematic random, radial
      sampling lines, was used for interactive measurements of distance from centre of
      lumen to points defining intima, media and adventitia thickness along the radial
      intercept, which were subsequently tabled for analysis of variance, calculations
      of (group-vessel) means, and related to stage of pathology. RESULTS: Pre
      atherosclerotic changes, before any localised changes in especially intima
      dimensions, are found, consisting of a process of gradual vascular widening,
      associated with temporally at least partly dissociated increases in width, which
      as a fraction of total vessel radius show a phased process. In these, the intima
      first increases, subsequently remains stable, and finally reduces in width
      proportionally to the increasing diameter. The media shows a similar initial
      increase, on average stabilising in the third phase after reaching a plateau
      value in the second. The adventitia, already increasing in phase 1, continues to
      increase in phase 2, accelerating in phase 3. The complex process, as found,
      occurs systematically in all vessels, is distributed circumferentially, and
      precedes the development of localised lesions of the intima. CONCLUSIONS: The
      findings suggest the existence of a diffuse complex of changes, consisting of a
      gradual vascular widening followed by narrowing, with associated mural changes
      reflecting the atherosclerotic process.

PMID- 17183724
TI  - Regulated polyploidy in halophilic archaea.
AB  - Polyploidy is common in higher eukaryotes, especially in plants, but it is
      generally assumed that most prokaryotes contain a single copy of a circular
      chromosome and are therefore monoploid. We have used two independent methods to
      determine the genome copy number in halophilic archaea, 1) cell lysis in agarose
      blocks and Southern blot analysis, and 2) Real-Time quantitative PCR. Fast
      growing H. salinarum cells contain on average about 25 copies of the chromosome
      in exponential phase, and their ploidy is downregulated to 15 copies in early
      stationary phase. The chromosome copy number is identical in cultures with a
      twofold lower growth rate, in contrast to the results reported for several other
      prokaryotic species. Of three additional replicons of H. salinarum, two have a
      low copy number that is not growth-phase regulated, while one replicon even shows
      a higher degree of growth phase-dependent regulation than the main replicon. The
      genome copy number of H. volcanii is similarly high during exponential phase (on
      average 18 copies/cell), and it is also downregulated (to 10 copies) as the cells
      enter stationary phase. The variation of genome copy numbers in the population
      was addressed by fluorescence microscopy and by FACS analysis. These methods
      allowed us to verify the growth phase-dependent regulation of ploidy in H.
      salinarum, and they revealed that there is a wide variation in genome copy
      numbers in individual cells that is much larger in exponential than in stationary
      phase. Our results indicate that polyploidy might be more widespread in archaea
      (or even prokaryotes in general) than previously assumed. Moreover, the presence
      of so many genome copies in a prokaryote raises questions about the evolutionary
      significance of this strategy.

PMID- 17183725
TI  - Wnt and Hedgehog are critical mediators of cigarette smoke-induced lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer death in the world, and
      greater than 90% of lung cancers are cigarette smoke-related. Current treatment
      options are inadequate, because the molecular basis of cigarette-induced lung
      cancer is poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that
      human primary or immortalized bronchial epithelial cells exposed to cigarette
      smoke for eight days in culture rapidly proliferate, show anchorage-independent
      growth, and form tumors in nude mice. Using this model of the early stages of
      smoke-induced tumorigenesis, we examined the molecular changes leading to lung
      cancer. We observed that the embryonic signaling pathways mediated by Hedgehog
      and Wnt are activated by smoke. Pharmacological inhibition of these pathways
      blocked the transformed phenotype. CONCLUSIONS/SIGNIFICANCE: These experiments
      provide a model in which the early stages of smoke-induced tumorigenesis can be
      elicited, and should permit us to identify molecular changes driving this
      process. Results obtained so far indicate that smoke-induced lung tumors are
      driven by activation of two embryonic regulatory pathways, Hedgehog (Hh) and Wnt.
      Based on the current and emerging availability of drugs to inhibit Hh and Wnt
      signaling, it is possible that an understanding of the role of Hh and Wnt in lung
      cancer pathogenesis will lead to the development of new therapies.

PMID- 17183726
TI  - A Bayesian network driven approach to model the transcriptional response to
      nitric oxide in Saccharomyces cerevisiae.
AB  - The transcriptional response to exogenously supplied nitric oxide in
      Saccharomyces cerevisiae was modeled using an integrated framework of Bayesian
      network learning and experimental feedback. A Bayesian network learning algorithm
      was used to generate network models of transcriptional output, followed by model
      verification and revision through experimentation. Using this framework, we
      generated a network model of the yeast transcriptional response to nitric oxide
      and a panel of other environmental signals. We discovered two environmental
      triggers, the diauxic shift and glucose repression, that affected the observed
      transcriptional profile. The computational method predicted the transcriptional
      control of yeast flavohemoglobin YHB1 by glucose repression, which was
      subsequently experimentally verified. A freely available software application,
      ExpressionNet, was developed to derive Bayesian network models from a combination
      of gene expression profile clusters, genetic information and experimental
      conditions.

PMID- 17183727
TI  - Rapid and highly informative diagnostic assay for H5N1 influenza viruses.
AB  - A highly discriminative and information-rich diagnostic assay for H5N1 avian
      influenza would meet immediate patient care needs and provide valuable
      information for public health interventions, e.g., tracking of new and more
      dangerous variants by geographic area as well as avian-to-human or human-to-human
      transmission. In the present study, we have designed a rapid assay based on
      multilocus nucleic acid sequencing that focuses on the biologically significant
      regions of the H5N1 hemagglutinin gene. This allows the prediction of viral
      strain, clade, receptor binding properties, low- or high-pathogenicity cleavage
      site and glycosylation status. H5 HA genes were selected from nine known high
      pathogenicity avian influenza subtype H5N1 viruses, based on their diversity in
      biologically significant regions of hemagglutinin and/or their ability to cause
      infection in humans. We devised a consensus pre-programmed pyrosequencing
      strategy, which may be used as a faster, more accurate alternative to de novo
      sequencing. The available data suggest that the assay described here is a
      reliable, rapid, information-rich and cost-effective approach for definitive
      diagnosis of H5N1 avian influenza. Knowledge of the predicted functional
      sequences of the HA will enhance H5N1 avian influenza surveillance efforts.

PMID- 17183728
TI  - Experimental rugged fitness landscape in protein sequence space.
AB  - The fitness landscape in sequence space determines the process of biomolecular
      evolution. To plot the fitness landscape of protein function, we carried out in
      vitro molecular evolution beginning with a defective fd phage carrying a random
      polypeptide of 139 amino acids in place of the g3p minor coat protein D2 domain,
      which is essential for phage infection. After 20 cycles of random substitution at
      sites 12-130 of the initial random polypeptide and selection for infectivity, the
      selected phage showed a 1.7x10(4)-fold increase in infectivity, defined as the
      number of infected cells per ml of phage suspension. Fitness was defined as the
      logarithm of infectivity, and we analyzed (1) the dependence of stationary
      fitness on library size, which increased gradually, and (2) the time course of
      changes in fitness in transitional phases, based on an original theory regarding
      the evolutionary dynamics in Kauffman's n-k fitness landscape model. In the
      landscape model, single mutations at single sites among n sites affect the
      contribution of k other sites to fitness. Based on the results of these analyses,
      k was estimated to be 18-24. According to the estimated parameters, the landscape
      was plotted as a smooth surface up to a relative fitness of 0.4 of the global
      peak, whereas the landscape had a highly rugged surface with many local peaks
      above this relative fitness value. Based on the landscapes of these two different
      surfaces, it appears possible for adaptive walks with only random substitutions
      to climb with relative ease up to the middle region of the fitness landscape from
      any primordial or random sequence, whereas an enormous range of sequence
      diversity is required to climb further up the rugged surface above the middle
      region.

PMID- 17183729
TI  - A systems biology strategy reveals biological pathways and plasma biomarker
      candidates for potentially toxic statin-induced changes in muscle.
AB  - BACKGROUND: Aggressive lipid lowering with high doses of statins increases the
      risk of statin-induced myopathy. However, the cellular mechanisms leading to
      muscle damage are not known and sensitive biomarkers are needed to identify
      patients at risk of developing statin-induced serious side effects. METHODOLOGY:
      We performed bioinformatics analysis of whole genome expression profiling of
      muscle specimens and UPLC/MS based lipidomics analyses of plasma samples obtained
      in an earlier randomized trial from patients either on high dose simvastatin (80
      mg), atorvastatin (40 mg), or placebo. PRINCIPAL FINDINGS: High dose simvastatin
      treatment resulted in 111 differentially expressed genes (1.5-fold change and p
      value<0.05), while expression of only one and five genes was altered in the
      placebo and atorvastatin groups, respectively. The Gene Set Enrichment Analysis
      identified several affected pathways (23 gene lists with False Discovery Rate q
      value<0.1) in muscle following high dose simvastatin, including eicosanoid
      synthesis and Phospholipase C pathways. Using lipidomic analysis we identified
      previously uncharacterized drug-specific changes in the plasma lipid profile
      despite similar statin-induced changes in plasma LDL-cholesterol. We also found
      that the plasma lipidomic changes following simvastatin treatment correlate with
      the muscle expression of the arachidonate 5-lipoxygenase-activating protein.
      CONCLUSIONS: High dose simvastatin affects multiple metabolic and signaling
      pathways in skeletal muscle, including the pro-inflammatory pathways. Thus, our
      results demonstrate that clinically used high statin dosages may lead to
      unexpected metabolic effects in non-hepatic tissues. The lipidomic profiles may
      serve as highly sensitive biomarkers of statin-induced metabolic alterations in
      muscle and may thus allow us to identify patients who should be treated with a
      lower dose to prevent a possible toxicity.

PMID- 17183732
TI  - Is a child's autism related to his father's age?

PMID- 17183731
TI  - Divalent metal ion coordination by residue T118 of anthrax toxin receptor 2 is
      not essential for protective antigen binding.
AB  - The protective antigen (PA) subunit of anthrax toxin interacts with the integrin
      like I domains of either of two cellular receptors, ANTXR1 or ANTXR2. These I
      domains contain a metal ion-dependent adhesion site (MIDAS) made up of five non
      consecutive amino acid residues that coordinate a divalent metal ion that is
      important for PA-binding. The MIDAS residues of integrin I domains shift
      depending upon whether the domain exists in a closed (ligand-unbound) or open
      (ligand-bound) conformation. Of relevance to this study, the MIDAS threonine
      residue coordinates the metal ion only in the open I domain conformation.
      Previously it was shown that the MIDAS threonine is essential for PA interaction
      with ANTXR1, a result consistent with the requirement that the I domain of that
      receptor adopts an open conformation for PA-binding. Here we have tested the
      requirement for the MIDAS threonine of ANTXR2 for PA-binding. We show that the
      toxin can bind to a mutant receptor lacking the MIDAS threonine and that it can
      use that mutant receptor to intoxicate cultured cells. These findings suggest
      that an open-like configuration of the ANTXR2 MIDAS is not essential for the
      interaction with PA.

PMID- 17183733
TI  - New cough-cold products on their way.

PMID- 17183730
TI  - A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin
      cyclophosphamide for locally advanced breast cancer.
AB  - BACKGROUND: Aberrant DNA methylation and histone deacetylation participate in
      cancer development and progression; hence, their reversal by inhibitors of DNA
      methylation and histone deacetylases (HDACs) is at present undergoing clinical
      testing in cancer therapy. As epigenetic alterations are common to breast cancer,
      in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor
      magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide
      in locally advanced breast cancer to assess their safety and biological efficacy.
      METHODOLOGY: This was a single-arm interventional trial on breast cancer patients
      (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent,
      patients were typed for acetylator phenotype and then treated with hydralazine at
      182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30
      mg/kg, starting from day -7 until chemotherapy ended, the latter consisting of
      four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days.
      Core-needle biopsies were taken from primary breast tumors at diagnosis and at
      day 8 of treatment with hydralazine and valproate. MAIN FINDINGS: 16 patients
      were included and received treatment as planned. All were evaluated for clinical
      response and toxicity and 15 for pathological response. Treatment was well
      tolerated. The most common toxicity was drowsiness grades 1-2. Five (31%)
      patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient
      progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had
      residual disease <3 cm. There was a statistically significant decrease in global
      5mC content and HDAC activity. Hydralazine and magnesium valproate up- and down
      regulated at least 3-fold, 1,091 and 89 genes, respectively. CONCLUSIONS:
      Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition,
      and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide
      treatment is safe, well-tolerated, and appears to increase the efficacy of
      chemotherapy. A randomized phase III study is ongoing to support the efficacy of
      so-called epigenetic or transcriptional cancer therapy.

PMID- 17183734
TI  - Lactose intolerance in children and adolescents.

PMID- 17183735
TI  - Using "good" bacteria to prevent diarrhea caused by antibiotics.

PMID- 17183737
TI  - Product recalls. Recall: Small World toy vehicles.

PMID- 17183736
TI  - Driveway "back-over" injuries to children.

PMID- 17183738
TI  - Complicated grief. Looking for help when mourning persists and intensifies.

PMID- 17183739
TI  - ADHD update: new data on the risks of medication.

PMID- 17183740
TI  - Reviving the study of hallucinogens.

PMID- 17183741
TI  - Racial diversity and jury deliberations.

PMID- 17183742
TI  - Schizophrenia and the metabolic syndrome.

PMID- 17183743
TI  - Violence as a medical issue.

PMID- 17183744
TI  - Report from the XVI International AIDS Conference. ACTG 5142 compares class
      sparing regimens in treatment-naive patients.

PMID- 17183745
TI  - Report from the XVI International AIDS Conference. Efavirenz for high viral load
      and low CD4--a secondary analysis of ACTG 5095.

PMID- 17183746
TI  - Report from the XVI International AIDS Conference. SMART and DART: intermittent
      antiretroviral treatment is suboptimal and should be avoided.

PMID- 17183747
TI  - Report from the XVI International AIDS Conference. Integrase inhibitors.

PMID- 17183748
TI  - Report from the XVI International AIDS Conference. Extensively drug-resistant TB
      in HIV/TB-coinfected patients in rural South Africa.

PMID- 17183749
TI  - [Effect of depressive state on parameters of heart rate variability in patients
      with ischemic heart disease and correction of revealed disturbances with
      antidepressant tianeptine].

PMID- 17183750
TI  - [Clinical and vascular effects of betaxolol in patients with arterial
      hypertension].

PMID- 17183751
TI  - [Atorvastatin in correction of metabolic syndrome: clinico-economical assessment
      of efficacy].

PMID- 17183752
TI  - [Practical approaches to selection of beta-adrenoblocker for the treatment of
      cardiovascular diseases: novel evidence based data].

PMID- 17183754
TI  - U.S. chemists = immigrants.

PMID- 17183753
TI  - [Cardiovascular risk and possibilities of lowering it in patients with metabolic
      syndrome and type II diabetes mellitus. The role of fibrates].

PMID- 17183755
TI  - Integrative tumor board: metastatic breast cancer.

PMID- 17183756
TI  - Epithelioid hemangioma: morphological presentation on aspiration smears.
AB  - Epithelioid hemangioma (EH) or angiolymphoid hyperplasia with eosinophilia is an
      uncommon but distinctive lesion seen principally in the skin and subcutaneous
      tissue. The histopathology of this disease is very characteristic, but error in
      diagnosis is possible on cytopathology. There are very few case reports
      describing the cytomorphology of this lesion. We describe the findings of fine
      needle aspiration of two cases of EH both arising in the subcutaneous tissue of
      the head and neck. Both the cases were misdiagnosed on cytology with one case
      being misinterpreted for an epithelioid sarcoma and the other for a reactive
      lymph node. The cytological findings of these cases are described and the
      problems encountered in the diagnosis of this entity are highlighted in this case
      report.

PMID- 17183757
TI  - Primary intravascular synovial sarcoma: a disease of young adult women? Report of
      a case diagnosed by aspiration biopsy and review of the literature.
AB  - Intravascular synovial sarcoma (IVSS) is an extremely rare tumor with only four
      well-documented cases in the English literature. All tumors were located in large
      veins of the lower extremities or trunk in young women except for one case
      occurring in a 54-yr-old woman. We report here an additional case of IVSS arising
      from the superior vena cava in a 32-yr-old woman who presented with a cervical
      mass and superior vena cava syndrome. A fine-needle aspiration biopsy (FNAB) was
      performed and showed a malignant biphasic tumor with spindle cell and epithelioid
      components. The tumor cells were negative for CD31, CD34, factor VIII, desmin,
      smooth muscle actin, and S-100 protein, and had positive staining for vimentin
      and cytokeratin (AE1/AE3) predominantly in the spindle and epithelial components,
      respectively. A diagnosis of synovial sarcoma was made and confirmed in a
      subsequent transvascular biopsy demonstrating chromosomal translocation t(X, 18)
      by fluorescence in situ hybridization using a dual color, break-apart-style probe
      for SYT. Although clinically similar to previously reported IVSS, this is the
      first case arising in large veins of the upper portion of the trunk and diagnosed
      by FNAB.

PMID- 17183758
TI  - Clear-cell endocervical adenocarcinoma in a 19-year-old woman.
AB  - The incidence of adenocarcinoma of the cervix is increasing within the US, but
      this diagnostic category is not typically associated with teenaged patients. A
      report on a case of a 19-year-old woman, with no history of diethylbestrol
      exposure in uteri, diagnosed with clear-cell endocervical adenocarcinoma is made.
      Malignant glandular cells were detected on both conventional and Thin Prep
      gynecologic tests with histologic confirmation. Human papilloma virus (HPV) high
      risk type results were negative in this particular case. The patient's
      unremarkable medical and sexual history prompted us to review the diagnostic
      criteria and pathogenesis of the disease.

PMID- 17183759
TI  - A death record book from Lancaster County, Pennsylvania (1858-1918).  Part 2: K
      through Z.

PMID- 17183760
TI  - Cytologic diagnosis of ciliated hepatic foregut cyst.
AB  - Ciliated hepatic foregut cyst (CHFC) is a rare, benign, solitary cyst occurring
      most often in the left lobe of the liver. CHFCs are typically found incidentally
      during radiologic imaging, surgical exploration, or autopsy. Only six cases of
      CHFC diagnosed by fine needle aspiration have been reported in the literature. We
      describe a CHFC diagnosed by aspiration in a 70-yr-old woman who presented with a
      2-yr history of abdominal discomfort. The radiologically benign-appearing lesion
      was located in the subcapsular area of segment IV of the liver. The aspirate
      contained benign ciliated columnar cells and goblet cells suspended in mucoid
      material. Sections from a cell block demonstrated pseudo-stratified bronchial
      type epithelium with mucin secreting cells and an absence of cartilage,
      characteristic of CHFC. Mucin-containing goblet cells stained with alcian blue.
      The neuroendocrine cells within the bronchial-type epithelium stained for
      calcitonin and synaptophysin. On follow-up, a computed tomography (CT)
      demonstrated the cyst to be unchanged, but as the patient continued to have pain,
      sclerosis of the cyst was planned. The diagnosis of CHFC by fine needle
      aspiration and its distinction from other solitary cysts of the liver may prevent
      unnecessary surgical exploration and excision.

PMID- 17183761
TI  - The development of the charitable landscape: the construction of the Lancaster
      County Almshouse in regional context.

PMID- 17183763
TI  - HIV infection on the rise worldwide: U.N. report.

PMID- 17183762
TI  - Mitochondrial disorder, diabetes mellitus, and findings in three muscles,
      including the heart.
AB  - The authors describe the case of a 50-year-old man with chronic progressive
      external ophthalmoplegia (CPEO), diabetes mellitus (DM), and coronary artery
      disease. The patient had no cardiac conduction abnormalities. During coronary
      artery bypass surgery, his heart and two skeletal muscles were biopsied. All
      three muscles showed ragged red fibers. The heart muscle showed significant
      glycogen accumulation. Analysis of mitochondrial DNA (mtDNA) showed a 5019-base
      pair deletion, with no duplications. There were morphologically abnormal
      mitochondria in all 3 muscles, with clinically apparent difference in
      preservation of function. The combination of diabetes mellitus and mtDNA deletion
      is fortuitous, as they can be causally linked. The cardiac pathology allows
      speculation about the possible adaptive processes that may occur in the heart in
      DM. There are few reported cases with CPEO and excess glycogen in the heart. Most
      show deposition of fat and poorer clinical outcomes as compared to those with
      glycogen deposition. This observation may lend support to the hypothesis that in
      the myocardium, adaptive responses are mediated via changes in glucose handling,
      whereas alterations in fat metabolism likely represent maladaptation.

PMID- 17183764
TI  - The two hundred year history of the Lancaster County Almshouse and Hospital.

PMID- 17183765
TI  - Bacteriophage research: its deeper significance for science.

PMID- 17183766
TI  - Overweight, obesity, and mortality.

PMID- 17183767
TI  - Cerebral aneurysms.

PMID- 17183768
TI  - Managed competition in Florida health care: its strengths and weaknesses.

PMID- 17183769
TI  - [Tachocomb plates efficacy in prevention of lymphorrhea in radical operations for
      gastric cancer].

PMID- 17183770
TI  - [Combined transplantation of pancreatoduodenal complex and kidney].

PMID- 17183771
TI  - [One-stage grafting of ascending aorta and aortic valve with multiple myocardial
      revascularizations].

PMID- 17183772
TI  - [A case of severe critical lower limb ischemia due to atherosclerosis].

PMID- 17183773
TI  - [Disruption of aortic bifurcation].

PMID- 17183774
TI  - [Heterotopy of pancreatic tissue as a cause of chronic pancreatitis. Typical and
      rare cases].

PMID- 17183775
TI  - [Intermuscular myxoma of the pelvis].

PMID- 17183776
TI  - [Cystic tumors of the pancreas].

PMID- 17183777
TI  - The lost way: community mental health in Maryland, 1960-75.

PMID- 17183778
TI  - Research from the National Institutes of Health, National Institute of Diabetes
      and Digestive Kidney Disease, and Charles R. Drew University of Medicine and
      Science High School Student Research Program--Summer 2005.

PMID- 17183779
TI  - The science of well being: An integrated approach to mental health and its
      disorders.

PMID- 17183781
TI  - The social brain hypothesis of schizophrenia.

PMID- 17183780
TI  - The feminine side of bootlegging.

PMID- 17183782
TI  - Establishing vertebrate paleontology at Chicago's Field Columbian Museum, 1893
      1898.

PMID- 17183783
TI  - The rise and fall of a pedagogical empire: the Board of State Charities and the
      Indiana philosophy of giving.

PMID- 17183784
TI  - A Sinai Hospital retrospective.

PMID- 17183785
TI  - A year in the life: the Home Relief Society in 1964.

PMID- 17183786
TI  - [Wegener's granulomatosis].

PMID- 17183787
TI  - [Oral squamous cell carcinoma in north-eastern Hungary. II. Etiological factors].
AB  - The purpose of this study is to determine the possible etiological factors of
      oral squamous cell carcinoma (OSCC) in North-Eastern Hungary. The medical records
      of 119 randomly selected patients with OSCC admitted to the Department of
      Maxillofacial Surgery of the Faculty of Dentistry, University of Debrecen were
      reviewed. The following risk factors were investigated: tobacco and alcohol
      consumption, dental status, rural vs. urban residence, and high risk HPV
      infection. The presence of HPV DNA has been evaluated by polymerase chain
      reaction from the tissue samples. Results were correlated with clinical data. At
      the time of diagnosis 65.5 percent of the patients were smokers. Under the age of
      45 the rate was 86.4%. Smoking significantly correlated with younger age, male
      gender, advanced clinical stages and alcohol consumption. The majority of the
      patients (75.5%) consumed alcohol, 41.1% regularly over the acceptable range.
      Drinking habit significantly correlated with younger age, male gender and tumor
      site (gingiva, retromolar region, tongue). HR-HPV types were detected in 42.8% of
      samples tested. HPV DNA presence was not related to gender, clinical stage,
      histological grade or other risk factors. Authors found weak correlation between
      HR-HPV positivity, younger patient age and better 5-year survival rate. The
      dental status was acceptable only in 12.6 percent of the cases. There was a
      correlation between dental status and age, smoking and drinking habits. No
      significant urban-rural differences were found. In the study population the most
      important risk factor for developing oral cancer is tobacco smoking followed by
      alcohol consumption. Avoidance of tobacco smoking and a reduced amount of
      alcohol, together with healthy nutrition and regular dental care should be
      emphasized.

PMID- 17183788
TI  - [A biomechanical study of the mechanical stress transmission of dental implants
      using finite element analysis. Part II. Experiments].
AB  - In the first part of this two-part study the possible uses of finite element
      analysis in studying the stress transmission of dental implants were reviewed. In
      the present second part our own experiments are presented. In the first series
      the effect of the geometric parameters and load types on mechanical stresses
      arising around cylindrical implants in bone were studied with 2D and 3D finite
      element analysis. In the second series the stress transmissions of various
      implant geometries were compared and an attempt was made to determine the optimal
      implant shape from the point of view of stress transmission.

PMID- 17183789
TI  - [Long-term experience of immediate implant loading using DenTi implants. Part 1.
      Material, methods and experience in immediate loading of DenTi implants].
AB  - Immediate loading of dental implants have been widely used to retain and support
      crossarch partial dentures. Normally 3-6 months after implantation complete
      osseointegration is established, this period may be shortened with immediate
      loading of implants. The purpose of this study was to evaluate the factors that
      may influence the long-term success of immediate implant loading. The immediate
      loading technique with DenTi implants was introduced 12 years ago, and during
      this period the clinical results have been followed up on 257 DenTi implants in
      83 patients. 62 patients and with 263 implants placed with submerged technique
      were recruited into the control group. The retrospective long-term follow-up
      examination has revealed that the success rate of DenTi implants with traditional
      two stage surgery was 97.4%. The success rate of DenTi implants with immediate
      loading was 95.71%. According to the date of the success rata and prognosis of
      immediate loaded implants are comparable to the traditional two stage submerged
      implants.

PMID- 17183790
TI  - [Oral rehabilitation of a patient with Wilson-syndrome using MK1 bolt attachment.
      A case report].
AB  - The oral condition of neurologically compromised patients seemed to be worse as
      compared to the healthy population, which is confirmed by concrete data in case
      of epilepsy patients. The dental status of our 33 years old patient with Wilson
      syndrome showed the same situation. The Wilson-syndrome is a hepatolenticular
      degeneration, with the disfunction of copper excretion in liver. Toxic dose of
      copper is accumulated in liver, in the nuclei of central nerve system, in
      kidneys, and in cornea. Deficiency of coeruloplasmin characterizes the disease
      which might occur in a form of acute hepatitis, chronic active hepatitis,
      cirrhosis or hepatosplenomegaly without any symptom. Initial symptoms might
      usually be extrahepatic, with the presence of the green and golden brown Kayser
      Fleischer copper deposition. Treatment is necessary until the end of life, 1 g
      Penicillamine/ day. Our patient with Wilson-syndrome has been treated for 17
      years at the Department of Neurology Semmelweis University. Dystonia, speech
      disorder, and intention tremor are rampant among his symptoms. At the time of
      admittance to dental clinic, both the upper and lower dental arches belonged to
      class 2B according to the Fabian and Fejerdy classification of partial
      edentulousness. After root canal fillings and cementation of dowel cores, an
      upper and lower fix and removable partial denture combination was made. Oral
      hygiene was controlled every three months. Dentures are worn for half a year
      without complaint.

PMID- 17183791
TI  - [The role of the oral flora in the pathogenesis of aspiration pneumonia].
AB  - The bacterial pneumonia is one of the most frequent complications leading to
      death among hospitalized patients. The morbidity and mortality of pneumonia is
      extremely high in the intensive care units and in chronic nursing stations,
      especially in institutes dealing with old patients. The most common form of lung
      infection is the aspiration pneumonia. Periodontal diseases play an evident role
      in the etiology of aspiration pneumonia due to their effect to alter the oral
      bacterial flora. Authors review the significance of pathogen microorganisms
      originating from the oral cavity in the development of bacterial pneumonia. The
      extent of the affected population is discussed and the importance of their oral
      hygiene and bacterial flora is also specified. The bacterial, enzymatic and
      molecular pathomechanisms leading to aspiration pneumonia are described, and high
      risk populations and treatment types are determined. The possibilities of
      prevention methods for aspiration pneumonia are fully explained and recent
      directions of actual researches and proposals to minimize the incidence of this
      disease are summarized.

PMID- 17183792
TI  - [Distractios osteogenesis in maxillofacial surgery].
AB  - For more than one decade the extremity surgery already used distraction
      osteogenesis. This new therapy in the region of the maxillofacial surgery (in the
      case of malformation of the maxilla and mandible) was adapted from the extremity
      surgeons. The authors summarized and classified the methods and history of the
      osteodistraction surgery based on literature. The indication fields, the used
      protocols and the most common distractor types are listed. The authors emphasized
      the multidisciplinary feature of the therapies, underlined the leading role of
      the orthodontist. With presenting their own two mandible distraction case reports
      they introduced the practical use of the distractors while using intra- and
      extraoral devices. They also emphasized the difficulties and failure
      opportunities. Their aim was to make suggestions for the further development of
      this method in our country.

PMID- 17183793
TI  - Extreme jobs: the dangerous allure of the 70-hour workweek.
AB  - Today's overachieving professionals labor longer, take on more responsibility,
      and earn more than the workaholics of yore. They hold what Hewlett and Luce call
      "extreme jobs", which entail workweeks of 60 or more hours and have at least five
      often characteristics-such as tight deadlines and lots of travel--culled from the
      authors' research on this work model. A project of the Hidden Brain Drain Task
      Force, a private-sector initiative, this research consists of two large surveys
      (one of high earners across various professions in the United States and the
      other of high-earning managers in large multinational corporations) that map the
      shape and scope of such jobs, as well as focus groups and in-depth interviews
      that get at extreme workers' attitudes and motivations. In this article, Hewlett
      and Luce consider their data in relation to increasing competitive pressures,
      vastly improved communication technology, cultural shifts, and other sweeping
      changes that have made high-stakes employment more prominent. What emerges is a
      complex picture of the all-consuming career-rewarding in many ways, but not
      without danger to individuals and to society. By and large, extreme professionals
      don't feel exploited; they feel exalted. A strong majority of them in the United
      States-66%-say they love their jobs, and in the global companies survey, this
      figure rises to 76%. The authors' research suggests, however, that women are at a
      disadvantage. Although they don't shirk the pressure or responsibility of extreme
      work, they are not matching the hours logged by their male colleagues. This
      constitutes a barrier for ambitious women, but it also means that employers face
      a real opportunity: They can find better ways to tap the talents of women who
      will commit to hard work and responsibility but cannot put in over-long days.

PMID- 17183794
TI  - Managing the right tension.
AB  - Of all the competing objectives every company faces, three pairs stand out:
      profitability versus growth, the short term versus the long term, and the whole
      organization versus the units. In each case, progress on one front usually comes
      at the expense of progress on the other. The authors researched the performance
      of more than 1000 companies worldwide over the past two decades and found that
      most struggle to succeed across the three tensions. From 1983 to 2003, for
      example, only 32% of these companies more often than not achieved positive
      profitability and revenue growth at the same time. The problem, the authors
      discovered, is not so much that managers don't recognize the tensions--those are
      all too familiar to anyone who has ever run a business. Rather, it is that
      managers frequently don't focus on the tension that matters most to their
      company. Even when they do identify the right tension, they usually make the
      mistake of prioritizing a "lead" objective within it-for example, profitability
      over growth. As a result, companies often end up moving first in this direction,
      then in that, and then back again, never quite resolving the tension. The
      companies that performed best adopted a very different approach. Instead of
      setting a lead objective, they looked at how best to strengthen what the two
      sides of each tension have in common: For profitability and growth,the common
      bond is customer benefit; for the short term and the long, it is sustainable
      earnings; and for the whole and its parts, it is particular organizational
      resources and capabilities. The authors describe how companies can select the
      right tension, what traps they may fall into when they focus on one side over the
      other, and how to escape these traps by managing to the bonds between objectives.

PMID- 17183795
TI  - Strategy and society: the link between competitive advantage and corporate social
      responsibility.
AB  - Governments, activists, and the media have become adept at holding companies to
      account for the social consequences of their actions. In response, corporate
      social responsibility has emerged as an inescapable priority for business leaders
      in every country. Frequently, though, CSR efforts are counterproductive, for two
      reasons. First, they pit business against society, when in reality the two are
      interdependent. Second, they pressure companies to think of corporate social
      responsibility in generic ways instead of in the way most appropriate to their
      individual strategies. The fact is, the prevailing approaches to CSR are so
      disconnected from strategy as to obscure many great opportunities for companies
      to benefit society. What a terrible waste. If corporations were to analyze their
      opportunities for social responsibility using the same frameworks that guide
      their core business choices, they would discover, as Whole Foods Market, Toyota,
      and Volvo have done, that CSR can be much more than a cost, a constraint, or a
      charitable deed--it can be a potent source of innovation and competitive
      advantage. In this article, Michael Porter and Mark Kramer propose a
      fundamentally new way to look at the relationship between business and society
      that does not treat corporate growth and social welfare as a zero-sum game. They
      introduce a framework that individual companies can use to identify the social
      consequences of their actions; to discover opportunities to benefit society and
      themselves by strengthening the competitive context in which they operate; to
      determine which CSR initiatives they should address; and to find the most
      effective ways of doing so. Perceiving social responsibility as an opportunity
      rather than as damage control or a PR campaign requires dramatically different
      thinking--a mind-set, the authors warn, that will become increasingly important
      to competitive success.

PMID- 17183796
TI  - Disruptive innovation for social change.
AB  - Countries, organizations, and individuals around the globe spend aggressively to
      solve social problems, but these efforts often fail to deliver. Misdirected
      investment is the primary reason for that failure. Most of the money earmarked
      for social initiatives goes to organizations that are structured to support
      specific groups of recipients, often with sophisticated solutions. Such
      organizations rarely reach the broader populations that could be served by
      simpler alternatives. There is, however, an effective way to get to those
      underserved populations. The authors call it "catalytic innovation." Based on
      Clayton Christensen's disruptive-innovation model, catalytic innovations
      challenge organizational incumbents by offering simpler, good-enough solutions
      aimed at underserved groups. Unlike disruptive innovations, though, catalytic
      innovations are focused on creating social change. Catalytic innovators are
      defined by five distinct qualities. First, they create social change through
      scaling and replication. Second, they meet a need that is either overserved (that
      is, the existing solution is more complex than necessary for many people) or not
      served at all. Third, the products and services they offer are simpler and
      cheaper than alternatives, but recipients view them as good enough. Fourth, they
      bring in resources in ways that initially seem unattractive to incumbents. And
      fifth, they are often ignored, put down, or even encouraged by existing
      organizations, which don't see the catalytic innovators' solutions as viable. As
      the authors show through examples in health care, education, and economic
      development, both nonprofit and for-profit groups are finding ways to create
      catalytic innovation that drives social change.

PMID- 17183798
TI  - Lift outs: how to acquire a high-functioning team.
AB  - More and more, expanding companies are hiring high-functioning groups of people
      who have been working together effectively within one company and can rapidly
      come up to speed in a new environment. These lifted-out teams don't need to get
      acquainted with one another or to establish shared values, mutual accountability,
      or group norms; their long-standing relationships and trust help them make an
      impact very quickly. Of course, the process is not without risks: A failed lift
      out can lead to loss of money, opportunity, credibility, and even native talent.
      Boris Groysberg and Robin Abrahams studied more than 40 high-profile moves and
      interviewed team leaders in multiple industries and countries to examine the
      risks and opportunities that lift outs present. They concluded that, regardless
      of industry, nationality, or size of the team, a successful lift out unfolds over
      four consecutive, interdependent stages that must be meticulously managed. In the
      courtship stage, the hiring company and the leader of the targeted team determine
      whether the proposed move is, in fact, a good idea, and then define their
      business goals and discuss strategies. At the same time, the team leader
      discusses the potential move with the other members of his or her group to assess
      their level of interest and prepare them for the change. The second stage
      involves the integration of the team leader with the new company's top
      leadership. This part of the process ensures the team's access to senior
      executives-the most important factor in a lift out's success. Operational
      integration is the focus of the third stage. Ideally, teams will start out
      working with the same or similar clients, vendors, and industry standards. The
      fourth stage entails full cultural integration. To succeed, the lifted-out team
      members must be willing to re-earn credibility by proving their value and winning
      their new colleagues' trust.

PMID- 17183797
TI  - Strategies to fight low-cost rivals.
AB  - Companies find it challenging and yet strangely reassuring to take on opponents
      whose strategies, strengths, and weaknesses resemble their own. Their obsession
      with familiar rivals, however, has blinded them to threats from disruptive, low
      cost competitors. Successful price warriors, such as the German retailer Aldi,
      are changing the nature of competition by employing several tactics: focusing on
      just one or a few consumer segments, delivering the basic product or providing
      one benefit better than rivals do, and backing low prices with superefficient
      operations. Ignoring cutprice rivals is a mistake because they eventually force
      companies to vacate entire market segments. Price wars are not the answer,
      either: Slashing prices usually lowers profits for incumbents without driving the
      low-cost entrants out of business. Companies take various approaches to competing
      against cut-price players. Some differentiate their products--a strategy that
      works only in certain circumstances. Others launch low-cost businesses of their
      own, as many airlines did in the 1990s--a so-called dual strategy that succeeds
      only if companies can generate synergies between the existing businesses and the
      new ventures, as the financial service providers HSBC and ING did. Without
      synergies, corporations are better off trying to transform themselves into low
      cost players, a difficult feat that Ryanair accomplished in the 1990s, or into
      solution providers. There will always be room for both low-cost and value-added
      players. How much room each will have depends not only on the industry and
      customers' preferences, but also on the strategies traditional businesses deploy.

PMID- 17183799
TI  - Health's ailment. A new congress may patch up a few problems but don't expect a
      cure.

PMID- 17183800
TI  - The scoop on carbs and fats. A new study tries to make sense of diet and the risk
      of heart disease.

PMID- 17183801
TI  - Not yet dearly departed.

PMID- 17183802
TI  - Extreme planning. Experts say New York's plan to restructure its healthcare
      system may prompt other states to consider doing the same.
AB  - In what could be a model for other states, New York's Commission on Health Care
      Facilities in the 21st Century last week recommended revamping the state's
      healthcare system, including closing nine hospitals. David Sandman, left, the
      executive director of the commission, says New York needs "to spend smarter and
      obtain better value.

PMID- 17183803
TI  - Changing Medicare, Medicaid ... may take more than GAO comptroller's letter.

PMID- 17183804
TI  - Hospitals' legal headache. After record year, feds keep pursuing False Claims
      cases.

PMID- 17183805
TI  - Tussling over benefits. HFMA accounting rules straddle AHA, CHA methods.

PMID- 17183806
TI  - Questioning HSAs. Many enrollees have no choice: study.

PMID- 17183807
TI  - CHA revenue down; ACHE's up. Catholic association hurt by investment
      restrictions.

PMID- 17183808
TI  - Conflict questions. Advisory board members say conflicts avoidable.

PMID- 17183809
TI  - RSNA brings out the balloons. Study discusses benefits of possible stent
      replacement.

PMID- 17183810
TI  - Gay groups question hospitals. Survey hopes to reveal how industry serves gays.

PMID- 17183811
TI  - Where the buck stops. Healthcare needs to stop blaming patients and take
      responsibility for errors.

PMID- 17183812
TI  - What I learned while on trial, Alvarado case shows that documentation is key to
      avoiding a costly legal ordeal.

PMID- 17183813
TI  - Losing strength. The '90s flurry of growth for doc unions has lost momentum, but
      organizers still believe the movement can be resuscitated.

PMID- 17183814
TI  - Easing the pain. Slowing prescription drug expense helps rein in costs for large
      employers.

PMID- 17183815
TI  - Rural hospitals need P4P help. Fewer resources can cause problems, study finds.

PMID- 17183816
TI  - Largest patient-satisfaction measurement firms ranked by total number of
      engagements in 2005.

PMID- 17183817
TI  - The hospital wars.

PMID- 17183818
TI  - What's toxic in toyland.

PMID- 17183819
TI  - What happens when they grow up.

PMID- 17183820
TI  - A terrible mystery.

PMID- 17183821
TI  - [Clinical research in cardiology: is this a goal realistic for general
      hospitals?].

PMID- 17183822
TI  - [Implantable cardioverter defibrillators: the role of community hospitals].

PMID- 17183823
TI  - [Off-pump coronary artery bypass: analysis of 1080 patients].
AB  - A consecutive cohort including 1080 patients undergoing "off-pump" myocardial
      revascularization was reviewed. An average of 2.22 bypass/patients was performed.
      The death-rate during the first 30 days after surgery was 0.65%. Four cases
      needed cross-over to on-pump. The postoperative events were: need of inotropic
      drugs (2.7%), atrial fibrillation (12.4%), myocardial infarction (6.6%). The
      extubation was performed before the first postoperative 24 h in 91.9% of cases.
      The majority of patients was discharged from hospital before 8 days after
      surgery. Off pump coronary artery bypass surgery exhibit good results for most of
      the patients even if they present multiple vessel disease and high operating
      risk.

PMID- 17183824
TI  - [Education for chronic cardiologic diseases in a transversal multidisciplinary
      unit: the experience of a general hospital center].
AB  - Treatments for congestive heart failure, hypertension and cardiovascular risk
      have significantly changed and have become more complex. The have also become
      more and more effective thanks to the results of great clinical studies that have
      enabled European and North-American societies to issues recommendations. The
      observance of the pharmacological and non-pharmacological treatments requires the
      education of patients and their family following guidelines that have been
      clearly defined by the European Society of Cardiology. This education, in which
      the technic of communication is very important, is common to a lot of chronic
      diseases and requires adequate material and human resources in order to have an
      optimal quality of treatment. In a society in which spending is on rise, getting
      such resources is not easy. However, putting in common resources of several
      departments can be a good solution. The experience of the Hospital Center of
      Douai (France) lead to the creation of a Transversal Education Unit at the end of
      the year 2003. This unit centralizes the efforts of several departments of care
      like pneumology, pediatrics, diabetology, nutrition and cardiology and allows
      patients suffering from co-morbidities to have access to various programs of this
      unit.

PMID- 17183825
TI  - [Variations in the management of patients with acute myocardial infarction in
      alpine hospitals compared to other French hospitals. Secondary analysis of the
      USIC 2000 study data].
AB  - OBJECTIVE: To compare processes of care for acute myocardial infarction among
      patients admitted to alpine vs other French hospitals. METHODS: Prospective
      observational study of patients with ST-elevation and non ST-elevation myocardial
      infarction of less than 48 hours hospitalized in 369 intensive care units in
      November 2000. RESULTS: Fifty-five patients were enrolled in nine alpine
      hospitals and 2265 patients in 360 other French hospitals. Patients baseline
      characteristics did not differ between the two groups with the exception of ST
      elevation myocardial infarction which was less frequent in patients admitted to
      alpine hospitals (71 vs. 83%, P = 0.02). Patients living in the alpine area were
      less likely to be admitted to hospitals with on-site cardiac catheterization
      facilities (42 vs. 60%, P < 0.01) although the use of primary (20%) and rescue
      (24%) percutaneous coronary intervention did not differ significantly between the
      two groups. There were no differences in the use of medical treatments between
      the two groups with the exception of low-molecular-weight heparin. The risk of in
      hospital death and complications did not differ significantly between the two
      groups while the risk of death at one year was lower in patients admitted to
      alpine hospitals (5 vs. 16%, P = 0.04). CONCLUSION: In 2000, a lower proportion
      of patients living in the alpine area had access to hospitals with cardiac
      catheterization facilities compared to other French patients. This finding
      supports the creation of an additional cardiac catheterization laboratory with
      experienced operators performing percutaneous coronary interventions 24 hours/7
      days and the implementation of an emergency medical care network for acute
      coronary syndromes in the alpine area.

PMID- 17183826
TI  - [Results of percutaneous coronary intervention in a hospital with a low case
      load].
AB  - Since efficacy of small volume centers performing coronary and angioplasty is
      questioned, we present our data for 2003. In 2003, 669 coronary examinations were
      performed in our unit (average age 68 years, 67% men) with 215 angioplasties. We
      take charge essentially Acute Coronary Syndrome (99%), with 37% ACS ST +. The
      radical approach was taken in 15% of cases. We used anti GP IIb/IIIa in 67% of
      cases (only abciximab), the rate of stenting was 84% with 43.6% of Direct
      Stenting. The primary angiographic results were good in 98% of cases. The rate of
      Restenosis was 6%. The hospital mortality was 2.8%. So we think that coronary and
      angioplasty in a small volume center can be performed with safety and a level of
      success in accordance with the data of the literature.

PMID- 17183827
TI  - [Hemodynamic instability and long-term lithium therapy].
AB  - Lithium is known to be responsible for many adverse events on the cardiovascular
      system. Among these events, it was experimentally noted that lithium could block
      the action of catecholamines on myocardium. The authors report the case of a
      patient under lithium therapy developing a myocardial infarction secondarily
      complicated of a severe cardiac failure. The inotropic support essential to
      balance hemodynamic could be raised only after lithium's stop. This example could
      be a clinical translation of the experimental effect previously observed.

PMID- 17183828
TI  - [Drug eluting stents in 2005: have the initial expectations been met?].
AB  - Drug eluting stent is a new technology aimed to prevent the development of
      neointimal hyperplasia and restenosis following percutaneous coronary
      intervention. This review describes the direction for their use at the present
      time and the future of their utilization with the summary of the principals
      clinicals trials.

PMID- 17183829
TI  - [Current treatment of acute type A aortic dissection. Surgical treatment and
      treatment of malperfusion syndrome].
AB  - Acute type A aortic dissection is a surgical emergency. Treatment is based on
      dissected ascending aortic replacement and correction of an associated aortic
      insufficiency. Catheterization of the axillary artery, open distal anastomosis
      and systematic resection of the intimal tear are the main surgical evolutions of
      the last years. They allowed to significantly reduce intraoperative mortality
      rate particularly due to bleeding. Thirty days mortality rate of operated aortic
      dissection is about 20 to 30%. Visceral malperfusion syndromes induced by aortic
      dissection represent an important cause of postoperative death. An early
      diagnosis and treatment appears necessary. Thoracoabdominal CT scan allows
      understanding mechanisms inducing malperfusion. Aortography and an emergency
      endovascular procedure allow restoring arterial blood flow before renal or
      mesenteric irreversible ischemia. Collaboration between radiologist,
      anesthesiologist and surgeon is necessary to optimize survival of acute type A
      aortic dissection.

PMID- 17183830
TI  - [Operative risk of heart valve surgery after 80 years].
AB  - The continuous prolongation of life expectancy in developed nations and the
      progress made in the surgical treatment of valvulopathy have substantially
      increased the number of octogenarians undergoing heart valve surgery with
      extracorporeal circulation. Most of them have calcified aortic stenosis and the
      valve is replaced with a bioprosthesis. At these ages, mitral valve disease-
      usually insufficiency--is predominantly treated by repair rather than valve
      replacement. In both cases, the etiology is primarily degenerative. In addition,
      an ever-increasing percentage of these patients require replacement of
      deteriorated bioprostheses. These octogenarians are exposed to surgical risk
      estimated to be about 9-10%, i.e. 2-3 times higher than that of patients under 70
      years of age, and even higher when surgery is a reintervention. Furthermore,
      morbidity affecting approximately an additional third of those undergoing surgery
      must be added to this mortality. Therefore, only half of the patients have
      uncomplicated surgical outcomes. Age is not the only factor enhancing the risk,
      which is also linked to comorbidities, preoperative functional class, stage of
      the evolving valvulopathy, and association of coronary artery disease. Predictive
      scores (Parsonnet, EuroScore) have been devised to evaluate the surgical risk to
      which these patients are subjected. Rigorous selection of patients with severe
      valvulopathy should enable potential candidates, willing to undergo an
      intervention, to be provided with indications for surgery sufficiently early so
      as to not enhance the risk by intervening too late.

PMID- 17183831
TI  - [Acute myocardial infarction: what is new?].
AB  - Current recommendations on the management of acute myocardial infarction and the
      use of thrombolysis are reviewed.

PMID- 17183832
TI  - Post-independence development of Indian pathology.

PMID- 17183833
TI  - Accuracy of cytologic diagnosis of central nervous system tumours in crush
      preparation.
AB  - The aim of this study was to assess the usefulness and accuracy of cytologic
      smears by making crush preparation as a diagnostic method, in central nervous
      system tumors. 278 patients with central nervous system tumors were investigated.
      In 98 cases, material was obtained intraoperatively during craniotomy and in 180
      cases stereotactic biopsies were done. In all the cases crush preparations were
      made, and cytologic diagnosis was correlated with final histologic diagnosis. 244
      out of 278 patients showed correlation with histopathological diagnosis. So, in
      present study diagnostic accuracy was 87.76%. In 18 cases no definite diagnosis
      was made due to inadequate material. Majority of the patients were in age group
      31 to 40 years (72 cases). The youngest patient was three years old and the
      eldest was 87 years old. The most common tumor in intracranial cavity was
      astrocytoma (56.68%), followed by meningioma (6.88%), medulloblastoma (5.66%) and
      ependymoma (5.56%). The most common tumor in intraspinal cavity was ependymoma
      (38.46%), followed by meningioma (23.07%) and schwannoma (23.07%). In conclusion,
      crush preparation is an effective, simple, rapid, relatively safe and reliable
      technique for the diagnosis of central nervous system tumors. Diagnostic accuracy
      of cytology with final histopathological report is established with accuracy rate
      of 87.76%.

PMID- 17183834
TI  - Osteoblastoma: a study of 12 cases.
AB  - This study comprises of 12 cases of osteoblastoma. There were 8 males and 4
      females, with a mean age of 17.8 years. The vertebral column, including the
      sacrum was the most frequent site (10 of 12 cases). Radiologically the lesions
      were lytic, well circumscribed and expansile. The histology consisted of
      intercommunicating osteoid seams lined by plump osteoblasts with numerous
      intervening ectatic stromal vessels. Despite these characteristic features, the
      distinction of osteoblastoma from osteoblastic osteosarcoma can at times be very
      problematic. The lack of lace-like osteoid or sheets of osteoblasts, and
      inconspicuous mitotic activity are useful distinguishing features. The purpose of
      this communication is to highlight the microscopic features for the correct
      recognition of osteoblastoma and its distinction from other osteoid forming bone
      lesions.

PMID- 17183835
TI  - Secondary and tertiary structure aberration of alpha globin chain in haemoglobin
      Q-India disorder.
AB  - Hemoglobinopathies are important inherited disorders with considerable high
      prevalence in Asia. Hemoglobin Q-India is a hemoglobinopathy that was first
      identified in India. Hb Q-India is caused by the mutation GAC --> CAC at codon 64
      of the alpha-1 globin gene. The correlation between this hemoglobinopathy and
      thalassemia was reported. Although primary structure of disorder Hb Q-India is
      well documented, the secondary and tertiary structures, which can help explain
      the pathogenesis of the Hb Q-India disorder is not known. In this study, amino
      acid sequence of human alpha globin was searched using ExPASY and used for
      further mutation to Hb Q-India disorder. The derived sequences, alpha globin
      chains in both normal and Hb Q-India disorder, were used for further
      investigation for secondary and tertiary structures. Modeling of these proteins
      for secondary and tertiary structures was done using the NNPREDICT server and
      CPHmodels 2.0 Server, respectively. In this study, the secondary and tertiary
      structures of human alpha globin chains of normal and hemoglobin Q-India disorder
      are calculated and presented. Based on this information, the main difference
      between the predicted alpha globin secondary structures of normal and Hb Q-India
      is an extra helix in the Hb Q-India. The predicted tertiary structure also
      supports this finding. The results from this study can be good data for further
      study on Hb Q-India disorder, which can bring to the further understanding on
      this hemoglobinopathy.

PMID- 17183836
TI  - Immunohistochemical study of the expression of epidermal growth factor receptor
      in benign prostatic hypertrophy, prostatic intraepithelial neoplasia and
      prostatic carcinoma.
AB  - The present study provides an analysis of immunohistochemical expression and
      localization of epidermal growth factor receptor (EGFR) in formalin fixed
      paraffin embedded specimens of prostate. Thirty-five cases each of benign
      prostatic hypertrophy (BPH) and prostatic carcinoma and 30 cases of prostatic
      intraepithelial neoplasia (PIN) were taken up for study. Streptavidin biotin
      peroxidase method was employed for immunohistochemical staining. EGFR positivity
      was observed in all the cases (100%) of BPH and PIN and in only 10 cases (28.5%)
      of prostatic carcinoma. In both BPH and PIN the basal cells revealed
      significantly higher intensity and percentage cell positivity than the luminal
      cells. Intensity and percentage of positively stained basal cells in BPH was
      higher than PIN basal cells but the difference was not statistically significant.
      The intensity and percentage cell positivity of BPH basal cells and PIN basal and
      luminal cells were significantly greater than the epithelial cells of prostatic
      carcinoma. Presently, the significance of variable expression of EGFR in various
      types of prostatic lesions is unknown.

PMID- 17183837
TI  - Dubin-Johnson syndrome--a clinicopathologic study of twenty cases.
AB  - Dubin-Johnson syndrome (DJS) is a rare benign chronic disorder of bilirubin
      metabolism, characterized by conjugated hyperbilirubinemia, darkly pigmented
      liver and presence of abnormal pigment in hepatic parenchymal cells. This is a
      retrospective study of twenty cases of DJS highlighting their major clinical and
      pathological findings. Liver biopsies were available in all the cases, obtained
      during a fourteen-year period (January 1991 to March 2005). The patients' age
      ranged from 7-63 years (median 21 years). These twenty cases comprised 13 males
      and 7 females. Major clinical manifestations were recurrent or persistent
      jaundice, abdominal pain and fever. Duration of illness ranged from 9 months to
      58 years (median 10 years). All of them had conjugated hyberbilirubinemia and
      total serum bilirubin levels ranged between 1.4-13 mg/dl (mean 4.4 mg/dl). Liver
      biopsies revealed presence of coarse granular brown pigment in the cytoplasm of
      hepatocytes more concentrated in the pericanalicular region and more prominent in
      centrilobular hepatocytes. Associated findings were presence of hepatitis B virus
      related chronic hepatitis (1), history of tubercular lymphadenitis (1), chronic
      cholecystitis in (2), coronary heart disease (1) and exacerbation during
      pregnancy (1).

PMID- 17183838
TI  - Thrombocytopenia--an indicator of acute vivax malaria.
AB  - Thrombocytopenia is frequently observed in vivax malaria but the exact mechanism
      has not been elucidated. We studied 27 cases of acute vivax malaria out of which
      24 cases had thrombocytopenia. This was the most common hematological finding.
      None had bleeding from any site. Anaemia and splenomegaly were not present in any
      of the cases. Platelet counts reverted to normal on treatment. Other causes of
      thrombocytopenia were ruled out by complete history and physical examination,
      dengue serology and blood culture. DIC was ruled out by peripheral smear
      examination and measurement of FDP levels. Our study stresses the importance of
      thrombocytopenia as an early indicator for acute malaria; a finding that is
      frequent and present even before anemia and splenomegaly set in. The possible
      mechanisms leading to thrombocytopenia in malaria have been discussed which
      include immune mechanisms, oxidative stress, alterations in splenic functions and
      a direct interaction between plasmodium and platelets.

PMID- 17183839
TI  - Sinus histiocytosis with massive lymphadenopathy--a review of seven cases.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML) also called as Rosai
      Dorfman disease is a rare histiocytic proliferative disorder of unknown etiology.
      Histological features currently define it. Persistent painless lymphadenopathy
      due to expansion of sinuses infiltrated with benign histiocytes and plasma cells
      and emperipolesis are the characteristic features of SHML. Our study includes
      seven cases (5 nodal and 2 extranodal) of SHML over a 5-year period whose slides
      and blocks were reviewed. IHC was performed on the main lesion, from a panel of
      S100, CD68, LCA, CD20, CD3, CD30, CD43, bcl2, cytokeratin and epithelial membrane
      antigen. In our series we have work up available in 7 cases out of which a
      detailed follow-up is available in 5 patients. Out of these 5 patients, 4 have a
      stable disease, while one developed histiocytic sarcoma after a gap of four
      years.

PMID- 17183840
TI  - HBsAg seropositivity among multi-transfused thalassemic children.
AB  - Thalassemia major patients are transfusion dependent; they are at high risk of
      post transfusion viral infections including Hepatitis B virus (HBV). The present
      study was undertaken to find out the proportion of HBV infection among multiple
      transfused patients. This cross-sectional study was conducted among thalassemic
      children of either sex between 2 to 13 years of age, who attended the tertiary
      care hospital (G. G. Hospital, Jamnagar). Subjects were divided according to
      number of transfusions and the immunization status. HBsAg was detected by ELISA.
      Of 90 patients 6 (6.6%) were positive for HBsAg. Of 29 patients who had received
      above hundred transfusions 3 (10.34%) were sero-positive for HBV. Un-immunized
      patients were at double risk for acquiring HBV infection. This study suggests
      that the screening of blood of donors for HBV should be strictly followed and
      implementation of immunization against HBV is a must, especially in a high-risk
      group like thallasemic patients.

PMID- 17183841
TI  - Giardia lamblia trophozoites in gastric biopsies.
AB  - To assess the prevalence of gastric giardiasis in gastric biopsies of patients
      with carcinoma stomach and in patients taking treatment for duodenal ulcer.
      Gastric biopsy specimens from 54 patients of carcinoma stomach and 100 antral
      biopsies from patients taking treatment for duodenal ulcer were included in the
      study. Sections were stained with haematoxylin and eosin, methylene blue and May
      Grunwald-Giemsa stains and examined for presence of Giardia lamblia trophozoites.
      Eight out of 54 (14.9%) biopsies of gastric carcinoma patients harboured
      trophozoites of Giardia lamblia. Associated H. pylori infection was present in
      all biopsies (8/8; 100%). Atrophy and intestinal metaplasia was present in 62.5%
      (5/8) and 25% (2/8) cases respectively. Sections from seven out of 35 patients
      (20%) taking treatment for duodenal ulcer showed presence of G. lamblia. H.
      pylori infection, gastritis and atrophy were found in 85.7% (6/7), 71.4% (5/7)
      and 28.6% (2/7) cases respectively. First gastric biopsy in these patients was
      negative for G. lamblia but 2nd and 3rd biopsies were positive. A careful search
      for G. lamblia trophozoites should be made while examining the gastric biopsies,
      especially in patients with carcinoma stomach, intestinal metaplasia, atrophic
      gastritis and those taking treatment for duodenal ulcer. This may help in
      indirect diagnosis of clinically unsuspected cases of intestinal giardiasis and
      may explain persistence of vague upper gastrointestinal tract (UGIT) symptoms
      despite clearance of H. pylori in patients on anti-ulcer therapy.

PMID- 17183842
TI  - Role of FAB classification of acute leukemias in era of immunophenotyping.
AB  - French-American-British classification for leukemias had been widely accepted due
      to its objectiveness and good reproducibility. WHO classification of leukemias
      was formulated in 1997 with a purpose of further enhancing the objectivity.
      However, the requirement of cytogenetics and immunophenotyping makes it difficult
      for many countries like India to put WHO classification in routine use. This
      study was carried to know the effectiveness of FAB classification in an era of
      technical advancement. A retrospective analysis of all acute leukemias over a
      period of 2 years was done. Out of total of 469 cases of acute leukemias, 193
      were diagnosed as Acute Lymphoblastic Leukemia (ALL), 200 as Acute Myeloid
      Leukemia (AML), and 76 cases diagnosed as Acute Leukemia, cytochemically
      undifferentiated. Hence, only 16% of all leukemias remained unclassifiable.
      Subclassification of AML cases revealed a much higher percentage of AML-M3, as
      compared to western literature. In conclusion, FAB classification, based on
      morphology and simple cytochemical stains, remains effective enough, although
      cytogenetics and immunophenotyping can add to diagnostic accuracy in some cases.

PMID- 17183843
TI  - Incidence of megaloblastic anaemia and its correction in leishmaniasis--a
      prospective study at BPKIHS hospital, Nepal.
AB  - Fifty (50) cases of Leishmaniasis were included in a prospective study after
      making the diagnosis based on the demonstration of L D Bodies on bone marrow
      aspirate. Hemoglobin (Hb) and total leucocyte count (TLC) were less than 10 gm/dl
      and 4000 per/ml respectively in 22 out of 50 cases. Among 50 cases, 30 showed
      macrocytic red cell and hypersegmented neutrophils on peripheral blood smear as
      features of megaloblastic anemia. Out of 30 cases of leishmaniasis with
      megaloblastic anemia, 10 cases showed decreased reticulocyte count. Bone marrow
      aspiration cytology showed megaloblastic maturation in erythroid series and giant
      metamyelocytes in myeloid series in all 30 cases of leishmaniasis with
      megaloblastic changes. Bone marrow iron was also increased in these cases.
      However megakaryocyte was normal in all. Among 30 cases of leishmaniasis with
      megaloblastic changes, 15 cases were treated with sodium antimony gluconate (SAG)
      only and other 15 with SAG, folic acid and Vit. B12. Rest 20 cases of
      leishmaniasis without megaloblastic changes were also treated with SAG only.
      After treatment with SAG alone as well as with SAG, folic acid and vit. B12,
      hemoglobin and TLC improved in all 50 cases. Of 15 cases of leishmaniasis with
      megaloblastic changes, who were treated with SAG, folic acid and vit. B12, the
      reticulocyte count reached at peak on the 7th day and normalized at the end of
      4th week. Red blood cells (RBC) also became normocytic normochromic and
      neutrophils became normal on peripheral blood smear. But no change was observed
      in reticulocyte count, RBC and white blood cell (WBC) morphology on peripheral
      blood smear in cases of leishmaniasis without megaloblastic changes and other 15
      cases of leishmaniasis with megaloblastic changes, who received SAG only.

PMID- 17183844
TI  - Is seroprevalence of HTLV-I/II among blood donors in India relevant?
AB  - Human T-cell lymphotropic virus type I/II (HTLV-I/II) is associated with certain
      hematologic and neurologic disorders. Seroprevalence studies demonstrate that the
      distribution of HTLV-I/II is heterogeneous worldwide and not specific to one
      region. Because blood is one of the major routes of transmission of the virus,
      blood banks of several countries routinely screen all blood donations for HTLV
      I/II. The aim of the present study was to assess the seroprevalence rate of HTLV
      I/II antibodies among Indian blood donors and to confirm the positive rates by
      polymerase chain reaction (PCR). Between Jan 2004 to May 2005, consecutive blood
      samples of 10,000 blood donors were collected at the blood bank of Armed Forces
      Medical College, Pune. The samples were screened for HTLV-I/II by enzyme-linked
      immunosorbent assay (ELISA) method. Screening resulted in 18 (0.18%) positive
      samples, of which 14 (77.8%) samples were also positive by PCR. The prevalence of
      HTLV-I/II carriers in India seems to be negligible and is not a major public
      health hazard. Hence, routine screening of Indian blood donors for antibody to
      HTLV-I/II is not warranted due to its low prevalence in India.

PMID- 17183845
TI  - Does c-erbB-2 expression have a role in medulloblastoma prognosis?
AB  - The prognosis of patients with medulloblastoma has remained same for the last two
      decades. This study evaluated the role of c-erbB-2 expression in medulloblastoma
      as a prognostic marker. Fifty cases of medulloblastomas were investigated for the
      expression of c-erbB-2 protein using immunohistochemistry. The expression of c
      erbB-2 was correlated with age, histology and disease-free survival (DFS). Thirty
      five (70%) tumors were c-erbB-2 positive. Immunoreactivity for c-erbB-2 receptor
      was observed as mixed cytoplasmic and membrane positivity of tumour cells. The
      mean DFS in c-erbB-2 positive cases was 19.81 months compared to 48.33 months in
      c-erbB-2 negative cases. c-erbB-2 positivity was found to be an independent
      predictor of poor outcome in medulloblastoma (p value < 0.05). No correlation of
      c-erbB-2 expression was observed with the age of patient and the histological
      type of tumour. Additionally, c-erbB-4 expression was also evaluated in these
      tumours. Thirty-three cases showed co-expression of c-erbB-2 and c-erbB-4
      proteins. However, c-erbB-4 expression alone was not associated with poor
      outcome, whereas its co-expression with c-erbB-2 was associated with shorter DFS
      (p < 0.05).

PMID- 17183846
TI  - Buerger's disease: clinical and histomorphological study.
AB  - There is an extremely high prevalence of Thromboangiitis Obliterans (TAO) or
      Buerger's disease (BD) in India among people of low socioeconomic class who smoke
      beedies (homemade cigarettes with raw tobacco). The aim of this study was to
      study the clinical and histo-morphological aspects of Buerger's disease with
      relevance to age at presentation in the local population. The study comprised of
      25 cases (all were men and were smokers) of clinically diagnosed BD based on
      Shionoya's criteria. The mean age was 47 years. The specimens consisted of 21
      biopsies, 2 end-arterectomies and 2 amputations. Formalin fixed, routinely
      processed, paraffin embedded tissue sections were stained with Haematoxylin and
      Eosin (H and E) and Verhoeff's elastic stain. They had claudication pain either
      in the ankle (5) or in the calf (2) or both (13). 24 had infrapopliteal disease
      and 9 showed upper limb involvement. 21 showed migratory thrombophlebitis also.
      Histomorphological presentation included the following features: Luminal
      thrombosis (14), fresh thrombosis (4), chronic inflammation in the vessel wall
      (10), within the thrombus (1) and around perivascular channels and nerve bundles
      (4). Internal elastic lamina showed reduplication in 13, undulation in 9 and
      fragmentation in 9 cases. Media of the vessel showed the following features:
      fibrosis (9), hypertrophy (9) and calcification (5) Adventitial haemorrhage,
      cholesterol clefts and atherosclerotic plaque formation were the other changes
      seen. In our study the following histopathological features were consistently
      seen. Thrombus (with or without recanalisation), inflammatory cell infiltrate
      (within the thrombus wall or periadventitial tissue), subintimal and medial
      fibrosis and changes in internal elastic lamina. These features were also
      highlighted in other studies. However in our study, medial hypertrophy and
      calcification were observed as additional features.

PMID- 17183847
TI  - Central neurocytoma: a clinico-pathological study of eight cases.
AB  - Central neurocytomas are benign neuronal tumours generally found in the lateral
      or third ventricles. They are rare, comprising < 1% of all brain tumours. It is
      frequently confused with other tumours of the central nervous system particularly
      oligodendroglioma. The present study was done to analyse the histopathological
      features including immunohistochemical profile of these rare tumours. Eight cases
      were taken up for the study. Seven of the cases had an intraventricular location
      and one was located outside the ventricles. Increased intracranial pressure was
      the most common presenting symptom. Microscopically all tumours were composed of
      small uniform cells with perinuclear halos and regular round nuclei. The tumour
      in extraventricular location showed atypical features. Immunohistochemistry
      showed positivity for neuronal markers. The present series highlights the
      characteristic clinical and pathological findings of this rare brain tumour.
      Immunostaining for neuronal markers are essential for distinguishing them from
      other small round cell tumours of the brain.

PMID- 17183848
TI  - Migration of steatonecrosis in pancreatitis.
AB  - Fat necrosis in pancreatitis has been reported in mesentery, gut serosa and
      distant sites like subcutaneous fat and fatty marrow. We present a case of
      chronic pancreatitis wherein fat necrosis was seen in the muscularis propria and
      submucosa of small intestine in addition to the serosa. Saponified fatty acid
      crystalloids, not seen in every case, were seen in these foci of fat necrosis.

PMID- 17183849
TI  - Serological study of parvovirus B19 infection in women with recurrent spontaneous
      abortions.
AB  - The feto-pathogenic association of parvovirus B19 (B19) has been sparingly
      studied in women with abortion, but not in women with recurrent spontaneous
      abortions (RSA). Serum samples from 116 women with RSA who were pre-screened for
      S-TORCH, Chlamydia trachomatis infections, anatomical, chromosomal, endocrinal
      abnormality and Rh incompatibility and those who had no such known causes of
      abortion were included in the study. Sera were also collected from 136 normal
      pregnant women and 120 normal non-pregnant women as disease and normal control
      respectively. All sera were tested at 1:400 dilutions for B19 IgM by in-house
      ELISA using cloned and baculovirus expressed VP1 and VP2 antigens of B19. The
      frequency of anti-B19 IgM antibodies in women with RSA was 19.8%, in pregnant
      females it was 11% and in normal non-pregnant female was 5%. Sera of 23 women
      with RSA which were positive for B19 IgM tested negative for B19 DNA by PCR.
      Patients with RSA should be screened for B19 infection and guidelines for
      treatment should emerge.

PMID- 17183850
TI  - Colonic cancer in young adults--a report of two cases.
AB  - Colonic carcinoma in young adults are rare and has a higher mortality and
      morbidity because of poor histological type and delay in diagnosis. We are
      reporting two cases of mucinous adenocarcinoma of caecum and sigmoid colon in
      young males.

PMID- 17183851
TI  - Pure red cell aplasia with malignant thymoma: a rarity.
AB  - Pure red cell aplasia sometimes accompanies thymoma. Herein we report a PRCA
      patient with malignant thymoma. Only two Indian cases of PRCA with malignant
      thymoma have been reported so far and six cases in the world literature, to the
      best of our knowledge. This paper describes a malignant thymoma in a 40 year old
      male who later on developed pure red cell aplasia 7 months after thymectomy.

PMID- 17183852
TI  - Bilateral mycotic cerebral abscess due to aspergillosis--a case report.
AB  - Aspergillosis of central nervous system is an uncommon infection mainly occurring
      in immunocompromised patient. It may be present in several forms: abscess,
      meningitis, mycotic aneurysm, infarction and in tumoral form. Here we report a
      case of cerebral aspergillosis presenting as bilateral frontal lobe abscess
      without evidence of any underlying systemic disorder or extracranial disease.

PMID- 17183853
TI  - Primary amyloidosis presenting as intrahepatic cholestasis.
AB  - Hepatic involvement in primary amyloidosis is not rare but is often clinically
      silent. A mild elevation of the serum alkaline phosphatase level and hepatomegaly
      are the most common findings. We report a case of primary amyloidosis in an adult
      male presenting with intrahepatic cholestasis where viral, drug, alcohol, and
      autoimmune etiologies were all excluded and the definite diagnosis was
      established by liver biopsy with Congo red staining. Subsequently the patient was
      found to have monoclonal light chain disorder.

PMID- 17183854
TI  - Post-irradiation carcinosarcoma of uterus--a case report.
AB  - The carcinosarcoma (malignant mixed mullerian tumour) of uterus is an aggressive
      neoplasm composing of malignant glands in the malignant stroma showing biphasic
      appearance. A 55 year old woman presented with discharge per vaginum of one month
      duration. Earlier she was given radiotherapy for squamous cell carcinoma of
      vulva, six years back. Abdominal examination was insignificant. USG suggested
      presence of post-radiation effect with uterine mass. Panhysterectomy was done and
      on histopathology, the diagnosis of carcinosarcoma (heterologous variant) was
      made. The case is being reported and discussed.

PMID- 17183856
TI  - Fetus in fetu or differentiated teratomas?
AB  - Two cases of congenital teratoma were operated upon. In view of the high degree
      of organoid differentiation of the teratomas with rudimentary limbs, intestine,
      brain-like and pulmonary tissues, it was difficult to distinguish it from fetus
      in-fetu. In the light of the data obtained and extensive review of related
      literature, we consider that fetus-in-fetu and teratoma may not be unrelated
      entities. Our cases support the view held that fetuses in fetu are highly
      differentiated teratomas.

PMID- 17183855
TI  - Auer rod-like inclusions in myeloma cells in a patient with IgG multiple myeloma.
AB  - Various inclusions have been reported in the past in plasma cells as well as
      myeloma cells. Most of these represent light chains of immunoglobulins which are
      concentrated within these cells. Auer rod-like inclusions in myeloma cells have
      been infrequently reported. They do not influence prognosis in patients with
      multiple myeloma but are more of a morphological variance. We report a patient of
      IgG myeloma with auer rod-like inclusions in myeloma cells in the bone marrow
      aspirates.

PMID- 17183857
TI  - Microfilariae in bone marrow aspiration smears, correlation with marrow
      hypoplasia: a report of six cases.
AB  - Microfilariae have been reported in various cytological preparations, however
      there are very few case reports describing microfilariae in bone marrow
      aspirates. We report six such cases with the interesting finding of marrow
      hypoplasia in five of these cases.

PMID- 17183858
TI  - Plasmacytoma of the clivus: a case report.
AB  - A 60-year-old male presented with headache and diplopia for 2 months. Computed
      tomography of the head showed a heterogeneously enhancing expansile lytic lesion
      in clival region. The patient underwent surgery and histopathological examination
      revealed it to be plasmacytoma of the clivus. The multiple myeloma work-up was
      negative. Solitary plasmacytoma localized to the skull base is extremely rare.
      Prior to this, only three case reports of plasmacytoma of the clivus have been
      described in the English literature.

PMID- 17183859
TI  - Primary chondrosarcoma of lung: case report and review of literature.
AB  - A case of primary chondrosarcoma of the left lung in 50 year-old man is
      presented. The tumor was diagnosed as primary chondrosarcoma of the lung after
      exclusion of any primary lesion elsewhere. Histologically, tumor consisted of
      predominantly chondromatous lesion. Immunohistochemistry showed that tumor cells
      positive for S-100 protein and vimentin, and negative for epithelial markers. On
      the basis of clinical, histological and immunohistochemical studies, the tumor
      was diagnosed as a primary chondrosarcoma of the lung.

PMID- 17183860
TI  - Juvenile hyaline fibromatosis: a case report.
AB  - Juvenile hyaline fibromatosis (JHF) is a rare, autosomal recessively inherited
      disorder characterized histologically by deposition of hyaline, collagen like
      substance aberrantly synthesized by the cells of the connective tissue and
      deposited within many organs, typically within the skin, gingiva, joints and
      bones. We report this rare case of Juvenile hyaline fibromatosis in a young boy
      who presented clinically with multiple papulonodular skin lesions, non tender
      soft tissue masses over the scalp, face, anterior chest wall, back, periarticular
      regions of the extremities with restricted mobility of joints and gingival
      hypertrophy. Calcifications were seen within the tumor shadows in the skull X
      Rays. Histopathological study revealed characteristic features consistent with
      Juvenile hyaline fibromatosis. We report this case in view of its rarity.

PMID- 17183861
TI  - Infective endocarditis due to Acinetobacter baumannii complex--a case report.
AB  - We report a case of infective endocarditis caused by Acinetobacter baumannii
      complex in a 27-year-old male patient. The patient presented with fever of five
      days duration, palpitation, dyspnea, cough and chest pain. He had undergone a
      surgical repair of ruptured aneurysm of sinus of valsalva a month before. The
      transthoracic echocardiogram revealed a large vegetation on the aortic valve.
      Three samples of blood for culture grew gram-negative pleomorphic coccobacilli
      within 24 hours which were identified by cultural and biochemical characteristics
      to be Acinetobacter baumannii complex. Antimicrobial susceptibility was performed
      by Kirby-Bauer method and the isolate were found to be resistant to ampicillin,
      Ciprofloxacin, Ceftriaxone, Gentamicin, Amikacin, Augmentin, Levofloxacin,
      Piperacillin-Tazobactam, Netilimicin and sensitive to Imipenem. Patient was
      initially treated with Ceftraixone and Gentamicin and subsequently with
      Ampicillin and Amikacin but did not respond to treatment and died of sepsis
      before therapy with Imipenem could be started.

PMID- 17183862
TI  - Nevoid basal cell carcinoma syndrome (Gorlin's syndrome): a case report.
AB  - A case of nevoid basal cell carcinoma syndrome is presented and its varied
      clinical manifestations and multi-system involvement are emphasised. Our case
      presented with an early onset of symptoms but sought medical help later on for
      progressively increasing jaw swelling and pain. On further evaluation, multiple
      pigmented skin papules, palmar pits, multiple jaw cysts, skull bone osteoporosis,
      bifid ribs and kyphosis were present. Systemic involvement was minimal. There was
      no significant family history.

PMID- 17183863
TI  - Fibromatosis of the breast--a case report.
AB  - A case of fibromatosis of the breast in a 30 years old female is described. Only
      a few cases have been previously reported. It is anticipated that fibromatosis of
      breast behaves in a similar fashion to fibromatosis occurring in other sites. It
      is a locally aggressive lesion which exhibits a high incidence of local
      recurrence following incomplete excision.

PMID- 17183864
TI  - Solitary intraductal papilloma of the breast--a diagnostic dilemma and the role
      of conferencing between surgeons and cytologist.
AB  - A 40 year female, presented with the complaints of spontaneous, sticky, blood
      stained discharge from the nipple of the left breast since 6 months. On
      examination there was no lump palpable in either breast. Cytology of the nipple
      discharge (ND) showed scanty cellularity consisting of tight papillary clusters
      of ductal cells in a hemorrhagic and inflammatory background. The nuclei were
      bland and showed degenerative atypia. Mammography showed no significant lesion.
      Our patient underwent microdochechtomy. Histopathology showed intraductal
      papilloma. Limitations of cytology must be kept in mind by both, the pathologist
      and the surgeon. The cytological diagnosis of a papillary tumor is provisional
      and the definitive diagnosis must await histological examination. In view of
      rarity of this lesion, combined with the overlapping of cytologic features in
      benign and malignant papillary lesions, conferencing and communication with the
      surgeon should be an integral part of patient evaluation and management. In our
      case this approach resulted in less radical excision of breast tissue.

PMID- 17183865
TI  - Synchronous vulvar intraepithelial neoplasia (VIN) of warty type and cervical
      intraepithelial neoplasia (CIN): case report.
AB  - Vulvar intraepithelial neoplasia is a precancerous lesion of the vulva, which has
      been referred to in the past with varied terminology. It can be associated with
      multicentricity of other neoplastic squamous lesions in the cervix and vagina. We
      report a case of vaginal intraepithelial neoplasia and concomitant cervical
      intraepithelial neoplasia in a 30 year old female. An attempt is made to put
      forth the recent terminology of vulvar intraepithelial neoplasia.

PMID- 17183866
TI  - Adenoid cystic carcinoma of ceruminous gland: a case report.
AB  - Adenoid cystic carcinoma of the external auditory canal (EAC) is a very rare
      malignant tumor and its diagnosis is frequently missed because of the superficial
      nature of biopsies. A 30 year old male presented with 6 months history of
      recurrent painful right ear discharge. On examination there was a nodule of 2 cms
      in diameter. The microscopic examination of the punch biopsy specimen of tumor
      revealed typical features of an adenoid cystic carcinoma. While reporting the
      biopsies of external auditory canal one should keep the adenoid cystic carcinoma
      as one of the possible differentials, especially if the biopsy is superficial,
      problem is recurrent and histopathological features suggest the granulation
      tissue.

PMID- 17183867
TI  - Benign fibrous histiocytoma of bone: a case report.
AB  - Benign fibrous histiocytoma (BFH) occurs commonly in soft tissues with very few
      cases of BFH of bone on record. We report a case of BFH of tibia in fifty year
      old male who presented with supracondylar fracture femur due to trivial fall and
      a brief review of literature.

PMID- 17183868
TI  - Carcinoma within a fibroadenoma: a case report.
AB  - Carcinoma within a fibroadenoma is an extremely rare occurrence with a reported
      incidence of 0.1% and is most often diagnosed incidentally on post-operative
      examination of excision biopsy specimens. One such case is reported here for its
      rarity and also for stressing upon the need for compulsory excision of all breast
      masses clinically diagnosed as fibroadenoma and for highlighting the importance
      of histopathological evaluation of all breast masses irrespective of their
      clinical diagnosis as benign.

PMID- 17183869
TI  - Mucinous cystadenoma of the renal pelvis with malignant transformation: a case
      report.
AB  - A mucinous cystadenoma of the renal pelvis with malignant transformation is an
      extremely rare entity. We discuss one such rare occurrence in a 62 year old
      female who developed mucinous nephrosis due to marked retention of mucin produced
      by the tumor.

PMID- 17183870
TI  - Metastatic adenoid cystic carcinoma of lung: a case report.
AB  - A 48 year old male patient, operated five years back for sub mandibular swelling
      proved on histopathologic examination to be adenoid cystic carcinoma presented in
      the ENT department, I. G. medical hospital with pain on both sides of the chest.
      CT scan of the chest showed multiple lesions of variable sizes. CT guided FNAC as
      well as biopsy of the lung lesion was performed. Cytodiagnosis and
      histopathological examinations revealed features of cribiform type of adenoid
      cystic carcinoma. This case is reported here for its metastasis to the lungs and
      prolonged survival even with multiple metastasis.

PMID- 17183872
TI  - Castleman's disease, intermediate type: a case report.
AB  - Castleman's disease or giant lymph node hyperplasia is a distinct form of lymph
      node hyperplasia. Histologically, there are 2 variants, hyaline vascular variant
      which occurs in 90% of the cases and plasma cell type which is rare. We
      encountered a 70 year old man with Castleman's disease showing intermediate
      features consisting of both hyaline vascular and plasma cell elements presenting
      as cervical lymphadenopathy. Following surgical excision, the patient was
      relieved of his constitutional symptoms and had no recurrence even after 6 months
      of follow-up.

PMID- 17183871
TI  - Diffuse multifocal chorangiomatosis of the placenta with multiple intestinal
      stenosis of the fetus: combination of rare causes for nonimmune hydrops fetalis.
AB  - Non-immune causes of hydrops fetalis are rare but frequently fatal.
      Identification of the cause for hydrops fetalis is essential to institute
      therapy. Chorangiomatosis and intestinal stenosis have not been previously
      reported as aetiological factors for the development of hydrops. We report a
      fetus born with hydrops associated with both of these conditions. A 1575 gms
      preterm neonate was born to a multigravida at 31 weeks of gestation. Emergency
      caesarean section was performed after detection of hydrops by prenatal
      ultrasonography. Baby had generalized edema at birth and died after 3 days due to
      progressive heart failure. At autopsy there was generalized edema and effusions.
      There were multiple stenotic segments in the intestine. Placenta showed numerous
      chorangiomas varying from 0.2 to 3 cm in diameter, hence diagnosed as diffuse
      multifocal chorangiomatosis. Examination of the placenta at neonatal autopsy is
      an essential part of assessment for hydrops fetalis. Chorangiomatosis is a rare
      and under reported condition which can cause prematurity, intrauterine growth
      retardation, pre-eclampsia and rarely hydrops fetalis.

PMID- 17183873
TI  - Clinicopathological study of dermolipoma--a report of four cases.
AB  - Dermolipomas are congenital solid choristomas usually located in the
      superotemporal fornix, near the lacrimal gland and lateral rectus muscle.
      Retrospective analysis of four consecutive cases of dermolipoma reported between
      Jan 1994 and July 2005 was done. Three cases were males and one was female and in
      all the cases swelling was first noted in the early childhood. Histologically
      they show squamous epithelium lined tissue containing mature adipose tissue in
      addition to bundles of dense collagen and adnexal structures which were present
      in all our cases. Surgical excision of dermolipoma is conservative and confined
      to the irritating dermal surface or the visible portion of the lesion.

PMID- 17183874
TI  - Disseminated herpes simplex infection with cystic fibrosis: a case report.
AB  - A 6 months old female infant presented with history of fever, cough and severe
      respiratory distress. There was past history of recurrent attacks of pneumonia.
      She succumbed to the illness after a hospital stay of 7 days. Postmortem revealed
      morphological evidence of cystic fibrosis along with herpes simplex infection of
      liver and adrenals. The co-existence of disseminated herpes simplex infection and
      cystic fibrosis is very rare.

PMID- 17183876
TI  - Nasal glial heterotopy in childhood: a case report highlighting the morphological
      and immunohistochemical features.
AB  - We present a case of a 5 months old infant who presented with difficulty in
      breathing and a visible intranasal swelling. Clinical examination revealed a
      reddish mass medial to the middle turbinate in the left nasal cavity. MRI was
      done and a provisional diagnosis of nasal glioma was suggested. The mass was
      surgically excised and sent for histopathology which showed it to be comprising
      of astrocytes and neuroglial fibers intermixed with a fibrovascular connective
      tissue stroma. The presence of Glial fibrillary acid protein (GFAP) confirmed the
      presence of glial tissue.

PMID- 17183875
TI  - Emphysematous pyelonephritis: report of 4 cases.
AB  - Emphysematous pyelonephritis is a rare, life endangering suppurative infection of
      the renal parenchyma and perirenal spaces. The disease is encountered mainly in
      patients with diabetes mellitus and is characterized by the production of
      intrarenal and, occasionally, perirenal gas. We present 4 cases of emphysematous
      pyelonephritis encountered in our hospital with review of the literature.

PMID- 17183877
TI  - Paratesticular malignant peripheral nerve sheath tumour: a case report.
AB  - Primary malignant peripheral nerve sheath tumours (MPNST) of intrascrotal extra
      testicular site are extremely rare with only few cases reported in literature.
      These are highly malignant tumours most often associated with neurofibromatosis.
      The incidence in general population is 0.001%. A 35-year-old male presented with
      swelling of the scrotal sac of three months duration. There were no features of
      neurofibromatosis. The lesion was excised and was diagnosed as MPNST. The patient
      developed recurrence within two months.

PMID- 17183878
TI  - Emergence of extended spectrum beta lactamase mediated resistance in neonatal
      septicemia.
AB  - This study was carried out in microbiology department of Gulbarga university,
      Gulbarga to find out the frequency of extended spectrum beta lactamase (ESbL)
      producing gram-negative bacilli isolated from neonatal septicemic cases. This
      study was carried out from Oct 2001 to June 2004. A total of 471 consecutive Gram
      negative bacilli were recovered during the study period from blood samples.
      Extended spectrum beta lactamase detection in gram-negative isolates was carried
      out by double disk synergistic method on Mueller Hinton agar. A susceptibility
      disk containing amoxicillin-clavulanate was placed as the inhibitor of beta
      lactamase in the center of the plate, and cefotaxime, ceftazidime, ceftriaxone
      and aztreonam disks were placed 30 mm (center to center) from the amoxicillin
      clavulanate disk. Enhancement of the zone of inhibition of the oxyimino-lactam
      caused by the synergy of the clavulanate in the amoxicillin-clavulanate disk was
      considered as evidence of ESbL production. Escherichia coli ATCC 25922 and K.
      pneumoniae ATCC 700603 were used as control strains. The frequency of ESbL
      producing gram-negative bacilli among the neonatal septicemic cases was 22.7%.

PMID- 17183879
TI  - Emerging vancomycin resistance in enterococci in India.
AB  - Infection caused by vancomycin resistant enterococci (VRE) leads to adverse
      outcome and is a real challenge. Despite increasing reports of VRE in different
      countries, there is scanty data on this issue from India. A total of 685
      enterococci were isolated from various clinical samples from January to December
      2004. Antimicrobial susceptibility was performed as prescribed by National
      Committee for Clinical Laboratory Standards (NCCLS). Vancomycin resistance was
      confirmed by minimum inhibitory concentration (MIC). Resistant phenotype was
      determined by Polymerase chain reaction (PCR). Of 685, 456 (67%) were E. faecalis
      and 229 (33%) were E. faecium. Resistance to various antibiotics in E. faecalis
      and E. faecium was as follows: ampicillin 33% and 54%, erythromycin 91% and 86%,
      ciprofloxacin 69% and 81%, tetracycline 50% and 54% and high level gentamicin
      resistance in 62% and 77% respectively. Vancomycin resistance was confirmed in 10
      (1.4%) cases by MIC and all had Van A phenotype by PCR. Emergence of vancomycin
      resistant enterococci is of great concern because of its epidemic potential and
      scanty therapeutic options. Prompt diagnosis and efficient infection control
      measures can restrict its spread.

PMID- 17183880
TI  - Extended spectrum beta lactamase producing gram negative bacilli in a tertiary
      referral hospital of Assam--experience with two methods.
AB  - Extended Spectrum Beta Lactamases (ESBL) are enzymes produced in some gram
      negative bacilli that mediate resistance to extended spectrum cephalosporins. 683
      clinical isolates of Escherisia coli and Klebsiella pneumoniae were studied for
      their capacity to produce ESBL. Isolates showing resistance to at least two of
      the third generation cephalosporins were studied for ESBL production by Jarlier
      technique and combination disc methods. Out of the 457 E. Coli and 226 Klebsiella
      pneumoniae isolated in Assam Medical College, 29.76% and 53.1% were resistant to
      two cephalosporins of which 29.41% and 29.16% strains showed production of ESBL.
      However, 6 (4.41%) and 16 (13.34%) strains additionally showed production of ESBL
      when tested with combination disc method. Though the Jarlier technique is
      popular, for detection of ESBL, yet false negative results warrants for
      alternative method. In the absence of molecular detection methods in routine
      clinical microbiology laboratory, combination disc method appears to be a better
      option.

PMID- 17183881
TI  - Simple scheme for identification of common species of enterobacteriaceae.
AB  - We propose a simple scheme for the identification of enterobacteriaceae species
      which routinely necessitates numerous biochemical tests and prolonged time span.
      In the scheme, family enterobacteriaceae is initially divided into four major
      groups depending on two important biochemical reactions viz. Lactose fermentation
      (L) and Methyl red test (MR). Each of the four groups, Group I (L + MR+), Group
      II (L + MR-), Group III (L- MR-), Group IV (L- MR+) can further be differentiated
      by using few tests. Eleven genera and 23 species can be identified by this scheme
      using limited biochemical tests. As many as 990 strains of enterobacteriaceae
      were subjected to standard biochemical tests and proposed simple scheme for
      identification. The discrepancy was observed only with 8 atypical strains of E.
      coli.

PMID- 17183882
TI  - Increased emperipolesis in megakaryocytes in a case of idiopathic
      thrombocytopenic purpura.

PMID- 17183883
TI  - Urinary bladder leiomyoma.

PMID- 17183884
TI  - Seroprevalence of HIV infection in patients with history of multiple blood
      transfusions.

PMID- 17183885
TI  - In vitro activity of azithromycin as an antipseudomonal agent.

PMID- 17183886
TI  - A report of two cases of Hashimoto's thyroiditis and synchronous parathyroid
      adenoma.

PMID- 17183887
TI  - The relationship between calculated effect-site sevoflurane levels and awakening
      from anaesthesia.
AB  - We have previously described a system that displays real-time estimates of effect
      site sevoflurane concentrations. Estimates of effect-site levels should be
      similar to minimum alveolar concentration (MAC) values, which are determined
      after allowing time for equilibrium. This study aimed to determine estimated
      effect-site sevoflurane concentrations at awakening from routine anaesthesia and
      to compare this with published estimates of MAC-awake. If these values were
      similar; this would validate our approach to the calculation of effect-site
      concentration. Sixty-five patients undergoing a variety of surgical procedures
      were observed. Prior to disconnection from the breathing circuit, forward
      estimates of effect-site sevoflurane were recorded. Patients were observed in the
      post-anaesthesia care unit and the time at which they responded to command was
      recorded.Age-adjusted effect-site sevoflurane at the time of awakening was
      determined. Correlation with patient, surgical and anaesthetic factors including
      age, gender; ASA status and intraoperative opioid usage were explored. Mean age
      adjusted calculated effect-site concentration at awakening was 0.59 (SD 0.27)
      vol%. This value is within the range of values determined for MAC-awake of
      sevoflurane. There was no correlation with any of the demographic or anaesthetic
      factors, but patients undergoing major surgery woke at a significantly lower mean
      sevoflurane level. These results support the use of effect-site sevoflurane
      concentration to guide administration of anaesthesia.

PMID- 17183888
TI  - Endotoxin stimulated interleukin-10 production is enhanced by adenosine. Possible
      key to septic shock associated immune deficiency?
AB  - The aim of this bench study was to investigate whether adenosine influences
      secretion of interleukin-10 (IL-O) in human whole blood culture stimulated with
      lipopolysaccharide. Whole blood from healthy human volunteers was mixed ex vivo
      in 1:1 ratio with RPMI 1640 culture medium and subsequently cultured at 37
      degrees C with or without adenosine (total of 120 microM added in four aliquots
      over two hours) in the presence or absence of 100 ng/ml lipopolysaccharide for
      four and eight hours, respectively. There was only a minimal IL-10 production
      after four hours of culture regardless of the experimental conditions. However,
      lipopolysaccharide stimulated whole blood cultures with added adenosine released
      large amounts of IL-lO after eight hours. The response was similar whether
      adenosine was added before (5.99 pg/ml/10(6) leucocytes) or after (10.35
      microg/ml/10(6) leucocytes) stimulation with lipopolysaccharide and
      interindividual variation was present. In conclusion adenosine enhances
      lipopolysaccharide stimulated IL-10 production in whole human blood and may
      contribute to the IL-10 mediated immune dysfunction in sepsis.

PMID- 17183889
TI  - Adenotonsillar surgery in morbidly obese children: routine elective admission of
      all patients to the intensive care unit is unnecessary.
AB  - Morbidly obese children undergoing adenotonsillectomy, often with co-morbid
      obstructive sleep apnoea, may be considered at a higher risk of postoperative
      respiratory compromise. This retrospective study aimed to assess the frequency
      and severity of postoperative respiratory complications in these patients and to
      identify preoperative risks factors for such morbidity. Medical and nursing chart
      review of all consecutive elective post-adenotonsillectomy admissions of morbidly
      obese children (defined as >95th centile for body mass index adjusted for age and
      gender) to our intensive care unit over a 30-month period was performed. A total
      of 26 morbidly obese children were identified. The majority (14/26) had an
      uncomplicated recovery following surgery. Of those cases that required
      postoperative intervention, 10 patients required supplemental oxygen with or
      without suctioning and/or repositioning alone, whilst two required continuous
      positive airway pressure therapy. No patient required re-intubation. An oxygen
      saturation nadir of < 70% and the presence of more than one central apnoea, noted
      on preoperative overnight polysomnography, were associated with postoperative
      respiratory complications requiring intervention. Although the intervention group
      were younger, more obese and had a higher respiratory disturbance index, none of
      these factors were statistically significant. Routine admission to the paediatric
      intensive care unit of all morbidly obese children undergoing adenotonsillectomy
      may be unnecessary, once a suitable high level of nursing is available in an
      alternative setting, to administer simple positional and suctioning intervention
      and to perform regular patient observation. Special consideration should be given
      to the postoperative nursing environment for those patients with a SaO2 nadir <
      70% noted preoperatively, indicating the presence of a significant central
      disease component.

PMID- 17183890
TI  - Increasing the use of an existing medical emergency team in a teaching hospital.
AB  - Cultural barriers in hospital ward staff may limit the use of a Medical Emergency
      Team (MET) service. In December 2000 the role of the existing Code Blue team in
      our hospital was expanded to incorporate review of patients fulfilling commonly
      employed MET criteria. Between January 2001 and June 2003, the average call rate
      was only 9.8 calls/ 1000 admissions. Anecdotal feedback and a group-administered
      questionnaire conducted in July 2003 demonstrated a number of obstacles to
      initiating calls and the system was modified in October 2004. Specifically,
      emergency response calls were separated into Code Blue calls (for
      cardiorespiratory arrests) and MET calls (with physiological and worried
      criteria). Further loud overhead chimes as well as anaesthetist and cardiologist
      attendance were used only in the case of Code Blue calls (suspected arrests).
      Finally, the heart rate and respiratory rate criteria for MET service activation
      were modified. In the 12 months before the intervention (October 2003 to
      September 2004) there were 817 emergency response calls and 51,963 admissions
      (15.7 calls/1000 admissions). In the 12 months after the intervention there were
      1349 emergency response calls (Code Blue plus MET calls) and 54,593 admissions
      (24.7 calls/1000 admissions [OR 1.59; 95% CI=1.45-1.73; P<0.0001]). Our findings
      suggest that increasing the use of an existing service to review patients
      fulfilling MET criteria requires repeated education and a periodic assessment of
      site-specific obstacles to utilization.

PMID- 17183892
TI  - Anaesthesia for implantation of the Jarvik 2000 Flowmaker LVAD.
AB  - The Jarvik 2000 Flowmaker is an intraventricular continuous axial flow left
      ventricular assist device. We describe the anaesthetic management and
      considerations for five patients with end-stage heart failure who underwent
      implantation of the Jarvik 2000 Flowmaker as a bridge to transplantation or as
      destination therapy.

PMID- 17183891
TI  - Near-hanging as presenting to hospitals in Queensland: recommendations for
      practice.
AB  - Near-hanging is an increasing presentation to hospitals in Australasia. We
      reviewed the clinical management and outcome of these patients as they presented
      to public hospitals in Queensland. A retrospective clinical record audit was made
      at five public hospitals between 1991 and 2000. Of 161 patients enrolled, 82%
      were male, 8% were indigenous and 10% had made a previous hanging attempt.
      Chronic medical illnesses were documented in 11% and previous psychiatric
      disorders in 42%. Of the 38 patients with a Glasgow Coma Scale score (GCS) of 3
      on arrival at hospital, 32% returned to independent living and 63% died. Fifty
      two patients received CPR, of whom 46% had an independent functional outcome.
      Independent predictors of mortality were a GCS on hospital arrival of 3 (AOR 150,
      CI 95% 12.4-1818, P<0.001), taking plain X-rays of the cervical spine (AOR 0.06,
      CI 95% 0.004-0.97, P=0.047) and contact with the ground (AOR 0.03, CI 95% 0.002
      0.62, P=0.02). Only 66% had imaging of the cervical spine performed with other
      imaging performed infrequently. There were three laryngeal, two hyoid bone and
      three cervical spine injuries and one carotid dissection. The number of cervical
      spine X-rays required to find a significant cervical spine fracture was 54. Near
      hanging presenting to hospital with a poor conscious state or even cardiac arrest
      can have a favourable clinical outcome. Radiological investigations are
      infrequently performed despite a low GCS precluding early accurate assessment.
      Given the general favourable outcome, an aggressive approach to searching for
      correctable injuries is recommended.

PMID- 17183893
TI  - Changes in clinical research in anaesthesia and intensive care from 1974-2004.
AB  - The purpose was to identify how the quality of anaesthesia research has improved
      from articles published in Anaesthesia and Intensive Care over 25 years. Original
      papers were included during the periods 1974-1978 and 2000-2004. Each article was
      classified according to principal research designs and the two five-year periods
      were compared. All interventional trials were evaluated according to the
      following a priori criteria: author number; ethics approval; informed consent;
      competing financial interest; eligibility criteria; sample size calculation;
      method of randomization; patients accounted for; blind assessment of outcome;
      adverse outcomes; statistical method stated; type I error; type II error; and
      anaesthetic department of origin. Comparisons of above criteria were made between
      the two groups using chi-square test or Fischer's exact test. Two-hundred-and
      ninety-two articles were reviewed in 1974-1978 and 529 articles were reviewed in
      2000-2004. Animal/laboratory articles decreased from 17.47% to 12.28% (P=0.05).
      Review articles decreased from 34.35% to 10.4% (P<0.0001). Descriptive trials
      increased from 28.4% to 52.72% (P<0.0001). Interventional trials increased from
      18.84% to 22.31% (P=0.269). Uncontrolled clinical trials decreased from 27.27% to
      12.71%, non-randomized controlled trials decreased from 50.91% to 7.63%, and
      randomized controlled trials increased from 21.82% to 79.66% (P<0.0001). All
      interventional trials criteria improved and were statistically significant except
      competing financial interest, method of randomization, patients accounted for;
      and type II error The quality of anaesthetic research has improved in Anaesthesia
      and Intensive Care over the past 30 years. However; there is still room for
      improvement.

PMID- 17183894
TI  - Facilitating learning in the operating theatre and intensive care unit.
AB  - Almost every aspect of anaesthetic and intensive care practice can be taught
      within the operating theatre and intensive care unit. This includes knowledge in
      the areas of medicine, anatomy, pharmacology, physiology, measurement and
      statistics, invaluable psychomotor and global skills and abilities, as well as
      the many important non-clinical aspects of anaesthesia and intensive care
      including effective communication, leadership, management, ethics and teaching.
      The operating theatre and intensive care unit offer many advantages and pose
      numerous challenges to education. This paper briefly discusses what can be taught
      in the operating theatre and intensive care unit, the educational challenges and
      benefits of teaching in these unique environments, implications for teaching and
      what consultants and trainees can do to positively influence the educational
      activity. The paper concludes with suggestions for facilitating learning in the
      operating theatre and intensive care unit including the Soldier's Five, practice
      vivas, skills training, endoscopic dexterity, interesting article exchange, in
      service sessions, electronic resources and use out of hours.

PMID- 17183895
TI  - Continuing medical education: a needs analysis of anaesthetists.
AB  - The continuing medical education (CME) needs of anaesthetists within Australia,
      New Zealand, Hong Kong, Malaysia and Singapore have been largely unknown. The aim
      of this study was to undertake a comprehensive survey of the attitude to CME,
      learning preferences, attitudes and abilities relating to self-paced material,
      literature and information searching, preferred content and preferred approach to
      CME of anaesthetists within these countries. A survey tool was developed and
      refined for ease of use by pilot-testing. The survey was mailed to 3,156
      anaesthetists throughout Australia, New Zealand, Hong Kong, Malaysia and
      Singapore. Three options for data return were offered; postal reply, facsimile
      and a data entry web-page. There were 1,800 responses, which represented a
      response rate of 57%. The demographics of the respondents were similar to the
      overall demographics of Fellows of the Australian and New Zealand College of
      Anaesthetists. A large majority of respondents (92%) stated that their
      involvement in CME improved patient care. However, almost half the respondents
      reported that they have difficulty either in participating in current CME
      activities (31%) or implementing new knowledge into their workplace (14%).
      Anaesthetists within this region appear to be motivated by the need to make
      better decisions based on independent standards of practice. While Australia is a
      world leader in flexible education, it is still emerging as a discipline.
      Flexible education may be used to facilitate anaesthetists' participation in CME
      activities and in implementation of new knowledge in their workplace.

PMID- 17183896
TI  - General practitioner anaesthesia survey 2006.
AB  - A survey was posted to all general practitioner anaesthetists in Australia who
      are currently involved in the Joint Consultative Committee on Anaesthesia (JCCA)
      accreditation process known as the Maintenance of Professional Standards program
      (MOPS). The survey was intended to gain information regarding accreditation,
      continuing medical education, caseloads, on call, work practices, attitudes and
      future work plans. The response rate was 70% (168/240). The majority of
      respondents worked in a rural location (73%) where there were no specialist
      anaesthetists (74%). Of the respondents, 89 were category A accredited, but only
      15% had this based on completion of the Advanced Rural Skills Curriculum
      Statement in Anaesthesia (ARSCSA) and examination. The mean number of sessions in
      anaesthesia worked per week was 2.8 (SD 2.2). Of the respondents, 69%
      administered more than 150 anaesthetics per year: 28% were on call more than 10
      times per month. General surgery, gastrointestinal endoscopy, obstetrics,
      gynaecology and orthopaedics were the most common specialties for which
      anaesthesia was provided. Eight percent of respondents stated that sedation
      comprised 81-100% of their caseload: 92% used propofol as part of their usual
      intravenous sedation technique: 90% provided anaesthesia for paediatric patients
      with a mean minimum age of 4.1 years (SD 3.4): 64% provided epidural
      anaesthesia/analgesia. The majority stated that specialist anaesthetists and
      hospital administrations were helpful and supportive. Eighty-two percent planned
      to continue or increase their current anaesthetic workload over the next five
      years. The JCCA MOPS program appears to provide a satisfactory pathway for
      training, accreditation and on-going education of general practitioner
      anaesthetists.

PMID- 17183897
TI  - An audit of intrathecal morphine analgesia for non-obstetric postsurgical
      patients in an adult tertiary hospital.
AB  - We conducted a retrospective audit of adult non-obstetric patients who had
      received a single dose of intrathecal morphine for postoperative analgesia. These
      patients were predominantly admitted to a regular postsurgical ward with strict
      hourly nursing observations, treatment protocols in place and supervision by an
      Acute Pain Service for the first 24 hours after intrathecal morphine
      administration. A total of 409 cases were examined for sedation score, incidence
      of respiratory depression and other side-effects, admission to the high
      dependency or intensive care unit and opioid-tolerance. Respiratory depression
      was defined as requiring treatment with naloxone (implying a sedation score of 3
      irrespective of respiratory rate), or a sedation score of 2 with a respiratory
      rate less than six breaths per minute. The patients were predominantly elderly
      (57.2% were over the age of 70 years) and 84.8% had undergone vascular surgery.
      Of the total of 409 cases, only one case of respiratory depression was observed.
      A total of 77 patients were admitted to high dependency or intensive care unit
      for various reasons including management of postsurgical complications and
      patient co-morbidities. Our findings suggest that elderly patients who receive
      intrathecal morphine analgesia can be safely managed in a regular postsurgical
      ward.

PMID- 17183898
TI  - Locally developed guidelines reduce immediate complications from percutaneous
      dilatational tracheostomy using the Ciaglia Blue Rhino technique: a report on 200
      procedures.
AB  - Ciaglia Blue Rhino percutaneous dilatational tracheostomy is used as an aid to
      ventilatory weaning. It carries an immediate complication rate previously
      reported in 100 consecutive patients by Fikkers et al at 6% for "major"
      complications and 30% for "minor" complications. Mortality has been associated
      with the procedure. Our institution has performed dilatational percutaneous
      tracheostomy since 1998 and used the Blue Rhino technique since 2002. Consensus
      guidelines were developed following initial experiences. They focus on
      preoperative risk assessment including levels of ventilatory support and
      anatomical considerations, seniority of staff use of bronchoscopy and capnography
      and correction of coagulopathies. Following introduction of the guidelines we
      conducted an audit of the first 200 Ciaglia Blue Rhino tracheostomies performed.
      There was an immediate major complication rate of 3% and minor complication rate
      of 18%. No deaths occurred within 24 hours of the procedure. We conclude that
      applying our consensus guidelines produced an immediate complication rate for
      Ciaglia Blue Rhino percutaneous dilatational tracheostomy below published audits.

PMID- 17183899
TI  - Anaesthesia for robot-assisted anatomic prostatectomy. Experience at a single
      institution.
AB  - Robot-assisted anatomic prostatectomy is an emerging technique for management of
      prostate cancer It requires a coordinated approach by anaesthetist and surgeon as
      the surgery is performed using a modified laparoscopic technique and is
      potentially of long duration in a Trendelenberg position. We describe some
      aspects of the surgical technique and our anaesthetic approach with the first 40
      cases at our institution. The mean hospital stay was 4.2 days and none of the
      patients required blood transfusion. A retrospective audit indicated that the use
      of epidural analgesia in the early postoperative period reduced opioid analgesic
      requirements.

PMID- 17183900
TI  - Recombinant human erythropoietin in severe anaemia: issues of dosing and
      duration.
AB  - The majority of Jehovah's Witnesses refuse blood product transfusion, even when
      it can be lifesaving. Treatment with recombinant human erythropoietin (RHuEPO) is
      a valuable adjunct in Jehovah's Witness patients undergoing surgery. A number of
      additional strategies, including acute normovolaemic haemodilution, intra
      operative blood salvage and reinfusion, iron and folate supplementation are also
      utilized to avoid blood transfusion. Critically ill patients have blunted
      erythropoietin production and decreased endogenous iron availability. This case
      report reviews the treatment of anaemia in critically ill Jehovah's Witness
      patients after surgery and discusses the potential need for higher RHuEPO dosing
      strategies and longer duration of therapy.

PMID- 17183901
TI  - Value of transoesophageal echocardiography for diagnosis of intraoperative tumour
      embolization.
AB  - Malignant neoplasms such as renal cell carcinoma may invade the inferior vena
      cava leading to a risk of pulmonary tumour embolization during surgical excision.
      Although massive pulmonary tumour embolism occurs relatively rarely, it can have
      catastrophic consequences. We report the case of an acute intraoperative
      pulmonary tumour embolism during resection of a renal cell carcinoma. The use of
      transoesophageal echocardiography allowed the immediate diagnosis and appropriate
      management of the underlying cause of acute haemodynamic instability. The role of
      transoesophageal echocardiography in the diagnosis of pulmonary embolism is
      discussed.

PMID- 17183902
TI  - Pseudoanaphylaxis.
AB  - Profound hypotension and cardiac arrest after commencement of combined spinal and
      general anaesthesia in a patient for knee replacement surgery raised the
      suspicion of anaphylaxis. This seemed to be confirmed when a mast cell tryptase
      test taken about 90 minutes after the onset of the hypotension was elevated.
      However, subsequent intradermal skin testing twelve weeks later did not identify
      a causal drug. Repeat mast cell tryptase at the time showed the same elevation,
      which led to the correct diagnosis of mastocytosis and a secondary diagnosis that
      the patient's hypotension and cardiac arrest were the result of her spinal
      anaesthesia. If the serum tryptase is elevated during the event but no allergic
      agent can be identified, a further serum tryptase should be taken several weeks
      later to exclude a persistent elevation due to mastocytosis.

PMID- 17183903
TI  - Successful resuscitation of an ASA 3 patient following ropivacaine-induced
      cardiac arrest.
AB  - A patient with severe myocardial disease and acute-on-chronic renal failure was
      undergoing a brachial plexus block for formation of an arteriovenous fistula when
      accidental intravascular injection of ropivacaine resulted in ventricular
      fibrillation. Cardiopulmonary resuscitation was instituted immediately and the
      advanced life support algorithm was followed until the return of sinus rhythm.
      Although, in comparison with bupivacaine, ropivacaine appears to be a safer local
      anaesthetic agent in the setting of intravenous injection, the emphasis on safety
      should remain a priority. Awareness of the risk of central nervous system and
      cardiovascular toxicity and preparation for immediate commencement of
      resuscitation in the event of toxicity remain of paramount importance.

PMID- 17183904
TI  - Tracheal resection for critical tracheal occlusion due to intraluminal tumour.
AB  - Anaesthesia for tracheal resection requires careful planning by an experienced
      team. We report a case of urgent tracheal resection for a vascular tumor in a 41
      year-old man who was a heavy smoker The tumour occupied most of his trachea. A CT
      reconstruction of the tumor assisted in planning. Perioperative tracheal laser
      therapy and cardiopulmonary bypass were not used due to concerns about excessive
      bleeding. Intraoperative airway management involved an upper endotracheal tube
      placed by the anaesthetist and a second, lower, endotracheal tube placed by the
      surgeon. The existing evidence for anaesthesia management of tracheal resection
      is currently limited to case reports. This case illustrates how preoperative
      imaging and careful planning can lead to a successful outcome, despite the
      potentially life-threatening nature of the pathology and the surgery.

PMID- 17183905
TI  - Tetanus in a subcutaneous drug abuser: ineffectiveness of intrathecal baclofen.
AB  - This report discusses the issues involved in the diagnosis and management of
      tetanus. A 29-year-old female with a history of illicit drug use presented with
      progressive tetany secondary to an abscess on her forearm from subcutaneous
      injections. She was managed in the intensive care unit for 29 days and was
      discharged to the ward. The main issue in her management was control of tetanic
      episodes interfering with ventilation and resistant to intrathecal baclofen.
      Other therapeutic strategies aimed at reducing spasms included magnesium,
      atracurium, pancuronium, midazolam, propofol and dantrolene. We conducted
      searches on Medline, PUBMED and the Cochrane Database of Systematic Reviews using
      the following terms: tetanus, treatment, therapy, drug abuse, magnesium, baclofen
      and human anti-tetanus immunoglobulin (hAIG). The current strategies involved in
      treating tetanus are discussed.

PMID- 17183906
TI  - Epidural analgesia for labour in a patient with a neural tube defect.
AB  - This report describes the use of epidural analgesia in a patient with a known
      neural tube defect. The patient had a severe form of spina bifida cystica which
      had been operated on in childhood. She had a neurogenic bladder but otherwise had
      preserved neurological function. She had an epidural catheter inserted in early
      labour; providing effective analgesia for an uneventful birth. This case outlines
      the severity of the cystica category of neural tube defects, the added anatomical
      challenges of previous surgery and the difficulties that may arise from the
      utilization of epidural analgesia. The case demonstrates that epidural analgesia
      can be utilized despite such a disorder A thorough history and examination are
      essential, as are the patient's informed consent and knowledge of possible
      complications.

PMID- 17183907
TI  - Sub-tenon block: a learning curve of 100 cases. Whose benefit?

PMID- 17183908
TI  - A cause for a non-invasive blood pressure cuff leak.

PMID- 17183909
TI  - Apnoea and consciousness disturbance following inadvertent inthrathecal injection
      of autologous blood during epidural labor analgesia.

PMID- 17183910
TI  - Drug therapy in congenital methaemoglobinaemia.

PMID- 17183911
TI  - Nasotracheal tube occlusion from adenoid trauma.

PMID- 17183912
TI  - Immediate postoperative prone ventilation in the management of transfusion
      related acute lung injury (TRALI) following infra-renal abdominal aortic aneurysm
      repair.

PMID- 17183913
TI  - Pulmonary oedema after mild upper airway obstruction in a pregnant woman
      receiving tocolytics.

PMID- 17183914
TI  - Kidney stone movement during lithotripsy under general anaesthesia: high
      frequency jet ventilation versus spontaneous ventilation.

PMID- 17183915
TI  - Iatrogenic puncture of laryngeal mask airway cuff.

PMID- 17183916
TI  - Motion sickness: advances in pathogenesis, prediction, prevention, and treatment.
AB  - Motion sickness has a major influence on modern traveling activities and the
      rapidly spreading engagement in virtual reality immersion. Recent evidence
      emphasizes the role of the otoliths in the pathogenesis of motion sickness, and
      several new theories may help explain its occurrence beyond the traditional
      sensory conflict theory. A promising new direction is the recently reported
      association of genetic polymorphism of the alpha2-adrenergic receptor with
      increased autonomic response to stress and motion sickness. Various physiological
      measures for the evaluation and prediction of motion sickness have been tested.
      However, no single parameter has yet been found to be of high enough sensitivity
      and specificity for the diagnosis or prediction of individual motion sickness
      susceptibility. A number of pharmacological and non-pharmacological
      countermeasures are used for the prevention and treatment of motion sickness. The
      non-pharmacological options include all procedures that reduce conflicting
      sensory input, accelerate the process of multi-sensory adaptation, and promote
      psychological factors which enable the subject to cope with his/her condition.
      The most effective anti-motion sickness drugs are central acting anticholinergics
      and H1 antihistamines; however, adverse effects on psychomotor performance may
      limit their use in drivers, pilots, and naval crewmembers. Recent studies may be
      relevant to our understanding of the link between motion sickness, migraine,
      vertigo, and anxiety. Based on these findings and on recent neurochemical data,
      the development of new anti-motion sickness agents is a promising field of
      investigation.

PMID- 17183917
TI  - Muscle oxygen supply during cold face immersion in breath-hold divers and
      controls.
AB  - INTRODUCTION: The human diving reflex is characterized by bradycardia, decreased
      cardiac output, and peripheral vasoconstriction, and has an oxygen-conserving
      effect both at rest and during exercise. However, the resultant time course and
      extent of muscle desaturation is unknown. METHODS: We used near-infrared
      spectroscopy to continuously measure the decrease in tissue oxygen saturation
      (StO2) in the calf muscle during a series of breath-holds. Subjects were seven
      trained divers (TD) and eight untrained controls (UC). Other measured variables
      included arterial blood pressure, heart rate, and arterial oxygen saturation
      (SaO2). Each subject performed five maximal apneas during face immersion in cold
      water with 2-min recovery intervals between breath-holds. RESULTS: On average,
      total apnea time for TD was significantly longer than for UC (772.6 +/- 40.9 s
      vs. 499.1 +/- 118.2 s, respectively). Further, TD had a more pronounced decrease
      in StO2 than UC (70.6 +/- 15.3% for TD vs. 87.9 +/- 6.1% UC for the fifth and
      longest apnea). When values for the two groups were compared at the mean
      breakpoint time for UC, there was no difference in StO2 and SaO2 remained at
      baseline. By contrast, at the same time point in all five apneas, UC experienced
      simultaneous, significantly larger reductions in SaO2 and StO2. DISCUSSION: These
      data indicate that TD have an attenuated diving reflex compared with UC at the
      same breath-hold times (the breakpoint for UC). In addition, muscle desaturation
      occurs earlier than arterial desaturation in both groups; the fact that this
      effect was less pronounced in TD suggests a training effect. This study provides
      further evidence for the oxygen-conserving effect of the human diving reflex in
      maintaining the oxygen supply of vital organs.

PMID- 17183918
TI  - Acclimation to intermittent hypobaric hypoxia modifies responses to cold at sea
      level.
AB  - INTRODUCTION: Residence at high altitude modifies thremoregulatory responses to
      cold stress upon return to lower altitude. These changes are difficult to explain
      since several stresses related to high altitude may interact, including hypoxia,
      cold, solar radiation, and physical exertion. We hypothesized that adaptation to
      hypoxia without cold exposure would produce at least part of the observed
      changes. METHODS: Five men underwent acclimation to intermittent hypoxia (AIH) in
      a hypobaric chamber (8 h daily for 4 d, and 6 h on the last day, 4500 to 6000 m)
      at 24 degrees C. Cold stress responses were tested during a whole-body standard
      cold air test (1 degrees C, 2 h at rest at sea level) both before and after AIH.
      RESULTS: Increased reticulocyte counts and percentages confirmed acclimation to
      hypoxia after AIH. Changes in thermoregulation during the cold test included
      lower mean skin temperature after 60-80 min (18.8 +/- 0.7 degrees C vs. 19.4 +/-
      0.7 degrees C); higher mean metabolic heat production (127 +/- 8 W x m(-2) vs.
      118 +/- 6 W x m(-2)); and lower heat debt (7.7 +/- 1.3 kJ x kg(-1) vs. 10.3 +/-
      1.2 kJ x kg(-1)), without significant change in rectal temperature. Time to onset
      for continuous shivering decreased after AIH (12 +/- 5 min vs. 21 +/- 6.3 min),
      and shivering activity occurred at higher mean skin but not rectal temperatures.
      CONCLUSION: AIH in comfortable ambient temperature leads to a normothermic
      insulative-metabolic general cold adaptation. We conclude that AIH modifies the
      thermoregulatory responses to cold at sea level without cold exposure leading to
      a cross-adaptation.

PMID- 17183919
TI  - Motion sickness during fore-and-aft oscillation: effect of the visual scene.
AB  - BACKGROUND: Repetitive braking and acceleration can cause carsickness, with the
      extent of sickness depending on the forward view outside the car. HYPOTHESIS: It
      was hypothesized that the visual scene would influence motion sickness caused by
      low-frequency, low-magnitude fore-and-aft oscillation in the laboratory. METHOD:
      There were 120 seated male subjects who were exposed to 30 min of 0.1-Hz fore-and
      aft oscillation at an acceleration magnitude of 0.89 m x s(-2) rms (a
      displacement of +/- 3.18 m). Subjects sat in a cabin with one of six scenes: 1)
      an internal view of two-dimensional black shapes on a white background; 2) an
      external view of the same two-dimensional shapes; 3) an external view of six
      horizontal black lines; 4) a 'real' three-dimensional external view; 5) no view
      (blindfolded); or 6) an internal collimated view of the two-dimensional shapes.
      Due to practical constraints, only conditions 1, 2, and 6 were tested in a
      balanced order. Ratings of motion sickness were obtained at 1-min intervals.
      RESULTS: Each of the six conditions caused motion sickness, with mean illness
      ratings that increased similarly over time regardless of viewing condition. The
      symptoms did not differ significantly between conditions and there was no
      difference in the risk of reaching an illness rating of 2, 'mild symptoms,'
      between the six viewing conditions. DISCUSSION AND CONCLUSIONS: With a larger
      number of subjects, a small mean effect of vision might be found with motions
      having similar frequencies or similar magnitudes to the conditions investigated
      here. Nevertheless, compared with the large effects of vision with some motions,
      it is concluded that the visual scene has little effect on sickness caused by
      pure fore-and-aft oscillation at a frequency of 0.1 Hz and an acceleration
      magnitude of 0.89 m x s(-2) rms.

PMID- 17183920
TI  - Rotation rate and duration effects on the somatogyral illusion.
AB  - INTRODUCTION: Aviation spatial disorientation mishaps remain a concern,
      especially due to their fatality rate. Some of the most insidious disorientations
      are due to vestibular stimuli in the absence of visual cues. A category of such
      disorientations are known as somatogyral illusions. METHODS: To determine the
      effects of spin rate and duration on the perception of the somatogyral illusion,
      we examined the subjective response of pilots and non-pilots to rotation around
      the yaw axis in a flight simulator in a manner that would mimic two vestibular
      illusions found in flight: the washout of the semi-circular canals following
      sustained turns, and the illusory counter-rotation following return to straight
      and level flight. There were 29 subjects (14 pilots) who were seated blindfolded
      in a flight simulator which accelerated to constant plateau rotation rates of 20,
      70, and 120 degrees x s(-1) and then decelerated to stationary; plateaus were 10,
      20, or 40 s. Subjects reported 1) the time when the perception of rotation ceased
      (i.e., the subjective time until washout was reached); 2) the relative magnitude
      of the counter-rotation experienced; and 3) the time until the perception of
      counter-rotation ceased. Subjects also manipulated a slider to provide a
      continuous subjective measure of their experience of rotation. RESULTS: The two
      time measures increased with increases in both the duration and magnitude of the
      spin. The increase in perceived washout time with spin rate was non-linear
      (geometric). There was an interaction between spin duration and spin rate on the
      experience of illusory counter-rotation magnitude such that at low rates, spin
      duration had no effect, but its effect increased at faster rates. The time
      constant of adaptation of the semicircular canals was estimated to be 8.3 s.
      DISCUSSION: The effects were validated against a model of semicircular canal and
      cupola adaptation, which predicted the data with high accuracy. Pilots and non
      pilots did not differ in their illusory experience.

PMID- 17183921
TI  - Midair collisions in U.S. civil aviation 2000-2004: the roles of radio
      communications and altitude.
AB  - BACKGROUND: Midair collisions are destructive to aircraft and often fatal to
      occupants, with the additional possibility of death and destruction on the
      ground. We sought to determine the characteristics of civil aviation mid-air
      collisions in U.S. airspace with focus on the altitudes at which the collisions
      took place and radio communications prior to the collisions. METHODS: Accident
      reports published by the National Transportation and Safety Board for the period
      2000-2004 were analyzed using descriptive statistics. Additional information was
      extracted from the narrative report of each accident. RESULTS: During the 5-yr
      period, 48 collisions in U.S. civil aviation occurred with 78 fatalities and 7
      persons severely injured. There were 46 aircraft destroyed and 37 substantially
      damaged. In 14 cases no radio communication was reported. In 19 cases there
      appeared regular radio communication with a tower or other aircraft. CONCLUSIONS:
      Midair collisions resulted in fewer severe injuries at lower altitudes.
      Visibility and weather were not contributing factors. Radio communication is
      recommended to assist aircraft where practical, but pilots need to be made aware
      of the limitations of radio communication for the avoidance of midair collisions.

PMID- 17183922
TI  - Alertness management in aviation operations: enhancing performance and sleep.
AB  - INTRODUCTION: Fatigue is an acknowledged safety risk in diverse operational
      settings. As a result, there has been growing interest in developing and
      implementing activities to improve alertness, performance, and safety in real
      world operations where fatigue is a factor. METHODS: A comprehensive Alertness
      Management Program (AMP) that included education, alertness strategies,
      scheduling, and healthy sleep was implemented in a commercial airline. An
      operational evaluation was conducted with 29 flight crewmembers, first when
      flying a standard schedule without AMP components (i.e., standard condition)
      compared with full AMP implementation, which included flying an innovative
      schedule that incorporated physiological sleep and alertness principles (i.e.,
      intervention condition). The evaluation included objective measures of sleep
      quantity (actigraphy), psychomotor vigilance task (PVT) performance, and
      subjective reports of daily activities and sleep. RESULTS: The results showed
      that the 3.5-h educational CD improved pre-education test scores from an average
      74% correct to a post-education average of 98%. Alertness strategies showed
      minimal changes, though the daily diary did not allow for refined evaluation of
      duration, frequency, and timing of use. The intervention condition was associated
      with significantly more sleep (1 h, 9 min; p < 0.01) during the trip period
      compared with the standard schedule. All performance metrics showed significantly
      better performance during the intervention condition trip schedule (p < 0.01)
      compared with the standard condition. DISCUSSION: This first-ever evaluation of a
      comprehensive AMP showed significantly improved knowledge, support for the use of
      alertness strategies, and increased sleep and performance during actual
      operations. The robust and consistent findings support the use of an AMP approach
      to effectively manage fatigue in operational settings.

PMID- 17183923
TI  - Long-term survivors of childhood malignancies--aeromedical dilemmas and
      implications.
AB  - Survival rates from childhood cancer have dramatically improved over the past
      three decades; average overall 5-yr survival rates are now > 75%. However, this
      has been achieved by treatments associated with significant morbidity that may
      present many years later. This review seeks to delineate the basic information
      necessary to evaluate flight-training candidates with a history of childhood
      cancer. We performed a literature review using the Medline database with
      appropriate search terms related to delayed morbidity and mortality associated
      with childhood cancer; we did not attempt to evaluate the risk of recurrent
      cancer. The neurological, cardiovascular, and pulmonary systems were identified
      areas of aeromedical concern. Central nervous disease and treatment-related
      effects may increase the risk of seizures or other neurocognitive sequelae. The
      cardiac toxicity of chemotherapeutic agents such as anthracyclines and radiation
      may cause late-occurring arrhythmia, cardiac failure, and sudden death, while
      available screening modalities are of limited value. Pulmonary disease and
      related treatment effects may cause a 9-fold increase of late-occurring pulmonary
      fibrosis and lung cancer, with increasing prevalence as long as 25 yr following
      the cancer diagnosis. Additionally, second malignancies may occur in up to 12.5%
      of cancer survivors at 25 yr after cancer diagnosis, affecting medical clearance
      for flight training. In summary, this review discusses the relevant aeromedical
      issues, including disabilities with specific relevance to the flying environment,
      risk estimation of late-occurring treatment complications, and possible
      interactions with occupational exposures in aircrew.

PMID- 17183924
TI  - Cutaneous infections with community-acquired MRSA in aviators.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of growing
      concern among community-based practices in medicine, particularly those in the
      military. The risk of colonization and infection by community-acquired MRSA (CA
      MRSA) is significantly higher among military members than that of the general
      population. The unique environment of the deployed, military aviator (impaired
      hygiene practices, close contact in warm, space-limited cockpits, and shared life
      support equipment) may increase risks of colonization, infection, and
      transmission of CA-MRSA and hence warrants the clinical attention of the flight
      surgeon. Studies of molecular genetics indicate that isolates of CA-MRSA contain
      a unique mobile genetic element (SCCmec type IV), indicating that CA-MRSA evolved
      separately from nosocomially acquired MRSA. Skin infections involving CA-MRSA are
      unlike their nosocomial counterparts in that CA-MRSA infections are susceptible
      to multiple classes of antibiotics and, on average, are clinically more
      aggressive. Awareness of this pathogen and appropriate clinical intervention can
      lead to prompt resolution of the infection and reduce rates of CA-MRSA
      colonization.

PMID- 17183925
TI  - Hemorrhage from an enlarged emphysematous bulla during commercial air travel.
AB  - Pulmonary bullae are a common late complication in patients with emphysema. Non
      communicating emphysematous bullae may expand during air travel when the ambient
      pressure is reduced, resulting in various forms of barotrauma including
      pneumothorax and air embolism. We report a 62-yr-old man with emphysema who
      developed hemoptysis during international commercial air travel. CT scan of the
      chest obtained after the travel showed air-fluid level in an enlarged bulla. He
      underwent resection of the bulla and had a full recovery. This is a unique
      presentation of stretch injury of a bulla as a form of pulmonary barotrauma
      occurring during commercial air travel. With the most recent ruling by the
      Federal Aviation Administration to allow patients with advanced chronic
      obstructive lung disease to travel by air with their own supplemental oxygen
      devices, physicians need to be aware of this type of pulmonary barotrauma and
      properly advise such patients who are planning to travel by air.

PMID- 17183926
TI  - Human systems integration in remotely piloted aircraft operations.
AB  - BACKGROUND: The role of humans in remotely piloted aircraft (RPAs) is
      qualitatively different from manned aviation, lessening the applicability of
      aerospace medicine human factors knowledge derived from traditional cockpits.
      Aerospace medicine practitioners should expect to be challenged in addressing RPA
      crewmember performance. METHODS: Human systems integration (HSI) provides a model
      for explaining human performance as a function of the domains of: human factors
      engineering; personnel; training; manpower; environment, safety, and occupational
      health (ESOH); habitability; and survivability. RPA crewmember performance is
      being particularly impacted by issues involving the domains of human factors
      engineering, personnel, training, manpower, ESOH, and habitability. RESULTS:
      Specific HSI challenges include: 1) changes in large RPA operator selection and
      training; 2) human factors engineering deficiencies in current RPA ground control
      station design and their impact on human error including considerations
      pertaining to multi-aircraft control; and 3) the combined impact of manpower
      shortfalls, shiftwork-related fatigue, and degraded crewmember effectiveness.
      Limited experience and available research makes it difficult to qualitatively or
      quantitatively predict the collective impact of these issues on RPA crewmember
      performance. CONCLUSION: Attending to HSI will be critical for the success of
      current and future RPA crewmembers. Aerospace medicine practitioners working with
      RPA crewmembers should gain first-hand knowledge of their task environment while
      the larger aerospace medicine community needs to address the limited information
      available on RPA-related aerospace medicine human factors. In the meantime,
      aeromedical decisions will need to be made based on what is known about other
      aerospace occupations, realizing this knowledge may have only partial
      applicability.

PMID- 17183927
TI  - Work-related musculoskeletal symptoms reported by female flight attendants on
      long-haul flights.
AB  - INTRODUCTION: Flight attendants working on long-haul international commercial
      airline operations exposed to ergonomic stressors are likely to experience work
      related musculoskeletal symptoms (WMS). To date, however, no studies
      investigating the extent of WMS experienced by this specific population have been
      published. The purpose of this study was to identify the prevalence and severity
      (frequency, duration, and intensity) of WMS experienced by female flight
      attendants working on long-haul international flights for one major airline.
      METHODS: A cross-sectional, mailed survey was conducted with female flight
      attendants randomly selected from a union membership list. Inclusion criteria
      were female flight attendants who had worked at least one long-haul international
      flight in the prior 3 mo and had worked at least 75 flight hours in the prior
      month. A total of 185 eligible flight attendants returned completed
      questionnaires (63% response rate). WMS in nine body regions were measured by the
      Nordic Musculoskeletal Questionnaire and the National Institute for Occupational
      Safety and Health Symptom Survey. RESULTS: The prevalence of WMS by body region
      ranged from 50% to 86%. Almost all (97%) of the flight attendants in this study
      experienced some level of WMS during the past year. The WMS tended to involve
      more than one body region, and the lower back was the most commonly affected body
      region. DISCUSSION: Female flight attendants working on long-haul international
      flights at one major airline showed a high prevalence of WMS, suggesting the need
      for replication studies with other airlines and the need for investigation into
      the risk factors associated with this substantial problem.

PMID- 17183928
TI  - Pilot alcohol violations reported in U.S. newspapers, 1990-2006.
AB  - INTRODUCTION: Alcohol violations by airline pilots are rare yet remain a public
      concern. Such incidents often generate widespread news coverage. This study
      examines the frequency and characteristics of alcohol violation incidents
      involving airline pilots reported in U.S. newspapers. METHODS: The database of
      Lexis-Nexis, which contains full-text articles for over 350 newspapers, was
      searched to identify alcohol violation incidents involving airline pilots in the
      U.S. between January 1990 and June 2006. Information pertaining to the pilot,
      flight, blood alcohol concentration (BAC), and consequence was ascertained for
      each incident based on the newspaper coverage. RESULTS: During the study period,
      newspapers reported on a total of 13 incidents of alcohol violations involving 17
      pilots. All but two of the incidents occurred during January 2002 through June
      2006. The majority (85%) of the incidents were first identified by airport
      personnel, such as security screeners, based on suspicion of alcohol use by the
      pilot. Subsequent alcohol testing revealed a mean BAC of 90 mg/dL (ranging from
      10 mg x dL(-1) to 182 mg x dL(-1)). Of the 17 pilots, 6 were known to be
      prosecuted criminally, including 5 who were sentenced to jail terms. DISCUSSION:
      Incidents of alcohol violations by airline pilots reported in U.S. newspapers
      have increased in recent years. This increase is likely due in part to increased
      detection resulting from enhanced aviation security and enforcement following the
      September 2001 terrorist attacks.

PMID- 17183929
TI  - Testicular tumor in an aviator.
AB  - Testicular tumor is an uncommon cancer mainly affecting males between 20 and 54
      yr of age. In the United States, approximately 2 to 3 new testicular cancer cases
      per 100,000 males occur each year. Testicular cancer is disqualifying for all
      classes of Federal Aviation Administration medical certificates, and
      consideration must be deferred to the FAA for Special Issuance (waiver)
      consideration. This article presents a case report of testicular cancer in an
      airline pilot, a brief discussion of testicular cancer, and the aeromedical
      implications of the diagnosis.

PMID- 17183930
TI  - You're the flight surgeon: modified measles in a commercial/reserve component
      pilot.

PMID- 17183931
TI  - This month in Aerospace medicine history--December 2006.

PMID- 17183932
TI  - Microwave oven to the stars?

PMID- 17183933
TI  - Transition: changing our approach to care for long-term pediatric transplant
      survivors.

PMID- 17183934
TI  - Role of adolescent development in the transition process.
AB  - Adolescent development is the normal process of transition from childhood to
      adulthood. Adolescents with transplants make the transition from pediatric to
      adult care within the context of other transitions in cognition, emotional
      attachments, autonomy, self-identity, sexuality, physical changes, life
      philosophy, and education/vocation. Healthcare providers can reduce their
      frustrations with this age group and optimize their care by understanding the
      impact of adolescent development on the transition process. In a busy clinic,
      attention to developmental issues can take on a low priority, but this does not
      have to be time consuming and may involve more of a perspective change than
      anything else. Both the adult and pediatric teams should remember that
      development does not stop at the time of transfer of care.

PMID- 17183935
TI  - The ON TRAC model for transitional care of adolescents.
AB  - This article describes the framework and clinical pathway for ON TRAC (Taking
      Responsibility for Adolescent/Adult Care), a model of transition care for
      adolescents with chronic health conditions, as applied to pediatric transplant
      transition. This model was developed in 1998 at Children's and Women's Health
      Centre of British Columbia; it provides a multidisciplinary approach to
      developmentally appropriate transition planning and skill building. The model is
      youth focused and family centered, and includes stages of transition care on the
      basis of the developmental stages and capabilities of adolescents. Important
      considerations for healthcare providers, specific tools for use in clinical
      settings, and case studies illustrate the use of the ON TRAC model in a pediatric
      transplant clinic. The ultimate goal of transition in the ON TRAC model is for
      all adolescents to reach their attainable levels of independence, self
      sufficiency, and self-worth while transferring safely and securely into adult
      healthcare services and adulthood.

PMID- 17183936
TI  - Smoothing things over: the transition from pediatric to adult care for kidney
      transplant recipients.
AB  - BACKGROUND: Transition is a planned movement of adolescents with chronic physical
      and medical conditions from child-centered to adult-oriented healthcare systems
      as opposed to a purely administrative event. OBJECTIVE: To evaluate the
      transition of pediatric kidney transplant recipients to the adult service at
      Guy's Hospital between 2000 and 2001 as compared with best practice from the
      literature, and to establish client satisfaction with the process. DESIGN: Data
      were collected by means of a retrospective review of case notes, clinician
      interview, and a patient satisfaction questionnaire, and analyzed by a single
      reviewer. MAIN OUTCOME MEASURES: Sixteen cases were analyzed with respect to
      their progress over the period of 1 year before and 1 year after transfer by
      looking at markers of adherence; a clinician's subjective assessment of overall
      graft stability before, during, and after transfer; and whether subjects chose to
      attend the transitional clinic. RESULTS: There was no qualitative difference in
      adherence or control among the patients who experienced the transitional clinic
      and those who did not. Patients who were considered stable and adherent before
      transition were not necessarily the same following transfer and vice versa.
      Patients who experienced the transitional clinic were not more satisfied as a
      group, although 9 of 11 thought their transition was "OK" or better. CONCLUSION:
      This is an extremely challenging area of pediatric nephrology; all patients need
      a high level of support. Services cannot be targeted to high-risk groups.

PMID- 17183937
TI  - There to here: young adult patients' perceptions of the process of transition
      from pediatric to adult transplant care.
AB  - BACKGROUND: An increased understanding of the transition process from pediatric
      to adult transplant care may inform strategies for facilitating the transfer of
      patients and ultimately improve outcomes of care. OBJECTIVE: To explore the
      transition process from pediatric to adult transplant care from the perspective
      of young adults. STUDY DESIGN: Using a qualitative case study approach, data were
      collected from transplant recipients through organ-specific focus groups, from
      transplant coordinators and nurse practitioners through interviews, and from
      electronic documents. Data were analyzed using an editorial format. RESULTS: The
      analysis identified 5 elements of transition: There to Here, Getting Ready, Frame
      of Mind, Making It Easier, and Giving Back. In addition, threaded throughout the
      elements were the themes People Are Important, Expectations of Us, and
      Information We Need. CONCLUSIONS: The transition for young people from a
      pediatric to an adult transplant center can be difficult and often traumatic.
      Young adults who transfer to adult care need to be better prepared for the adult
      center, made aware of the differences, and introduced to team members before the
      transfer. Transition programs that aim to improve the transition process should
      be developed for these patients.

PMID- 17183938
TI  - Medication adherence after heart transplantation: adolescents and their issues.
AB  - CONTEXT: Medication nonadherence among adolescent heart transplant recipients can
      have overwhelming negative consequences including rejection and mortality.
      Because of issues specific to adolescents such as peer pressure, risk taking,
      independence, self-image, and self-esteem, they are a population susceptible to
      nonadherence. Adherence may be associated with a supportive environment, fewer
      physical and cosmetic side effects, and a sufficient knowledge of therapies.
      Adherence also may be related to regimens with fewer medications, predominantly
      fewer immunosuppressive drugs. OBJECTIVE: To examine the differences in
      motivation between adolescents who are more adherent and those who are less
      adherent to their medication regimen following transplant surgery. DESIGN: A
      descriptive design and mixed methodology, including a modified written survey,
      the Frazier Noncompliance Inventory; a self-report measure of overall medication
      adherence; and an interview designed by the investigator. Interview questions
      were reviewed for content validity by nurse clinicians and researchers. SETTING:
      A heart transplant follow-up clinic in the southeastern United States. RESULTS:
      Findings for 2 participants revealed striking contrasts in adolescent issues and
      factors affecting adherence. These findings are presented in a case comparison.
      Data show that a supportive environment and knowledge of medications were
      significant in increasing self-responsibility and adherence in adolescent
      transplant recipients. Also, experiencing rejection early in treatment because of
      less adherence led to increased adherence for fear of further rejections or
      death.

PMID- 17183939
TI  - Pediatric to adult transition: a personal experience.
AB  - Transitioning from pediatric to adult transplant programs presents various
      challenges to the patient, his or her family, and the healthcare staff. In this
      personal, retrospective account of the issues associated with transitioning, a
      patient and a nephrologist provide insights into some of the problems they
      confronted.

PMID- 17183940
TI  - Transition of transplant patients with cystic fibrosis to adult care: today's
      challenges.
AB  - One of the most trying ordeals for patients with cystic fibrosis is moving from
      one care setting to another. When the patient is facing the crisis of failing
      health and the need for lung transplantation, the transition can seem even more
      overwhelming. In Toronto, patients are transferred from pediatric to adult care
      at age 18. Moving a teenager with cystic fibrosis to the adult system presents
      many challenges, and even greater challenges arise when the patient has received
      a lung transplant or is awaiting one. Two pediatric and adult cystic fibrosis
      teams have worked closely with the lung transplant teams to create a smooth
      transition system. This article outlines both programs and presents a case study
      to explore the challenges for the teams in deciding the best place to meet the
      needs of the patients and their families. These families offer us a look at
      coping with change at a time of great stress and at how we as healthcare
      providers can support them through the system.

PMID- 17183941
TI  - Caregivers of lung transplant candidates: do they benefit when the patient is
      receiving psychological services?
AB  - BACKGROUND: We recently demonstrated that a targeted psychological intervention
      has quality of life, mood, and social intimacy benefits for patients awaiting
      lung transplantation. OBJECTIVE: To evaluate the impact of the patient's
      participation in treatment on caregiver functioning. DESIGN AND INTERVENTION:
      Caregivers of patients participating in a randomized clinical trial designed to
      compare 2 telephone-based psychological interventions completed outcome measures
      at baseline and at 1 and 3 months after patients completed treatment. Patients
      were randomized to receive either supportive therapy (emotional and educational
      support) or quality-of-life therapy (a cognitive-behavioral intervention that
      provided specific intervention strategies to boost happiness and satisfaction in
      life domains that compromise overall quality of life). Caregivers did not
      participate directly in the interventions. Setting and Participants-Participants
      were 28 caregivers from a large lung transplant center in the southeastern United
      States. MAIN OUTCOME MEASURES: Quality of life (Quality of Life Inventory), mood
      disturbance (Profile of Mood States-Short Form), and social intimacy (Miller
      Social Intimacy Scale). RESULTS AND CONCLUSIONS: Caregivers reported higher
      quality of life and lower mood disturbance scores, and comparable social intimacy
      scores relative to the patients for whom they were caring. Caregivers whose
      patients received quality-of-life therapy reported vicarious gains in quality of
      life, mood disturbance, and social intimacy, relative to those whose patients
      received support therapy. Finally, the degree of change in patients' quality of
      life, mood disturbance, and social intimacy contributed significantly to
      predicting caregivers' functioning at the 3-month follow-up assessment. These
      findings suggest that telephone-based quality-of-life therapy has beneficial
      effects that extend beyond patients to their caregivers.

PMID- 17183942
TI  - Lung transplantation in adolescents and young adults with cystic fibrosis.
AB  - CONTEXT: Little is known about adolescents' and young adults' experience with
      cystic fibrosis while waiting for or after receiving a lung transplant. The
      psychological and psychosocial factors that may influence these patients'
      transplant outcomes are yet to be fully explored. OBJECTIVE: To explore the
      psychosocial impact of the lung transplant journey on adolescents and young
      adults with cystic fibrosis. DESIGN: A questionnaire-based pilot study was used
      to enable descriptive, comparative, and correlational analyses between
      pretransplant and posttransplant groups. SETTING: A major lung transplant unit in
      Australia. PARTICIPANTS: Twenty-seven patients (9 before and 18 after
      transplantation) participated in the study. The mean ages were 18.7 years (SD
      4.2) and 22.6 years (SD 3.9) in the pretransplant and posttransplant groups,
      respectively. RESULTS: In all domains of the Short Form 36 except Mental Health
      and Social Functioning, the posttransplant group had significantly higher scores
      (P < .05) compared to the pretransplant group. The Hospital and Anxiety and
      Depression Scale total Distress score in the posttransplant group was related to
      the number of rejection episodes (r = 0.47, P = .049) as well as hospital
      admissions (r = 0.51, P = .012), The number of rejection episodes was
      significantly related to patients' perceived level of self-efficacy (P = .025),
      importance to health (P = .001), and ease (P =.10) of monitoring their symptoms.
      CONCLUSION: This study provides some insight into the needs of adolescents and
      young adults with cystic fibrosis and the differences between those who are
      awaiting a transplant and those who have received a transplant. Assessing the
      young person's perceptions in relation to activities such as exercising,
      monitoring symptoms, and taking medications can give helpful insights into the
      transition phase, but require further research.

PMID- 17183944
TI  - Advanced practice organ procurement techniques: insertion of arterial catheters.
AB  - Placement of arterial catheters by organ procurement coordinators is becoming
      more common. Classroom and clinical training in this technique and provision of
      appropriate quality assurance and supportive policies/procedures by organ
      procurement programs will ensure the coordinators' success. This discussion
      reviews technical aspects of insertion of catheters into the radial, femoral, and
      axillary arteries, potential complications, and alternative noninvasive methods
      of measuring blood pressure.

PMID- 17183943
TI  - The effect of donor factors on human islet yield and their in vivo function.
AB  - BACKGROUND: A major problem in the islet field is the high selectivity exercised
      in accepting cadaveric pancreas for islet isolation. This practice is based on
      experience that indicates that islet yield and posttransplant function are
      related to donor demographics and injury mechanisms. OBJECTIVE: To examine
      factors influencing islets recovery and in vivo function with emphasis on donor
      related factors. METHODS: Islets were isolated from 99 human donor pancreata, and
      islet yield was reported as islet equivalent per gram pancreatic tissue. Donor,
      procurement, and isolation factors were collected for each isolation and
      correlation statistics were performed between these variables and islet yield.
      RESULTS: Results indicated a differential effect of enzyme mixes on yield with
      Collagenase P digestion most suitable for increased ischemic time (R2 = 0.1; P <
      .08), Liberase with small donor pancreas size and elevated preprocurement glucose
      (R2 = 0.15; P < .02), and Serva with female donors (R2 = 0.17; P < .06). Islets
      from 29 isolations were further tested by transplantation under the kidney
      capsule of immune-deficient NOD-SCID mice. Although all 29 preparations had
      acceptable in vitro perfusion parameters indicating viability, only 19 functioned
      in vivo with serum levels of insulin >5 U/mL and C peptide >1.5 ng/mL. No
      significant differences in donor, procurement, and isolation factors were evident
      between the islet preparations that functioned in vivo and those that were
      nonfunctional. CONCLUSIONS: These data demonstrate that although yield is
      affected by a variety of donor factors and enzyme mixes, these factors do not
      affect islet in vivo function.

PMID- 17183945
TI  - [Hypophosphatemia in the hospitalized patient].
AB  - BACKGROUND: Phosphate is an obligatory component of cellular function. Serum,
      levels are maintained within narrow levels by regulatory mechanisms. The normal
      range of phosphate concentration is 2.5-4.5 mg/dL. In certain clinical situations
      these mechanisms are insufficient and hypophosphatemia ensues. AIM: This study
      aimed to compare hospitalization course and clinical outcome of patients with
      moderate hypophosphatemia (1.0-2.0 mg/dl) with patients with extreme
      hypophosphatemia (< 1.0 mg/dL). METHODS: Patients who had at least one
      measurement of serum phosphate level of 1.0 mg/dL or less comprised the extreme
      hypophosphatemic group. Patients with at least one serum, phosphate level of
      between 1.0 and 2.0 mg./dL, but never had a phosphate level of less than 1.0
      mg/dL comprised the moderate hypophosphatemic group. Files of 50 consecutive
      patients who had extreme hypophosphatemia and 100 consecutive patients with
      moderate hypophosphatemia were retrieved and analyzed. RESULTS: The two groups of
      patients were similar with reference to age, gender ratio, background disease and
      indication for hospitalization. There was a higher proportion of obese patients
      in the moderate hypophosphatemia group. There was a higher proportion of patients
      who consumed alcohol on a regular basis before hospitalization in the extreme
      hypophosphatemic group. Patients suffering from extreme hypophosphatemia were
      more likely to be hospitalized in the intensive care unit and ventilated on
      hospitalization. Length of hospitalization was longer for the extreme
      hypophosphatemia group than for the moderate hypophosphatemia group. When
      comparing the group outcomes it was found that more patients with severe
      hypophosphatemia died. CONCLUSION: Severe hypophosphatemia is a severe metabolic
      derangement. It appears in critically sick patients, who should be followed
      closely and treated properly. The clinical relevance of moderate hypophosphatemia
      was not checked in this study.

PMID- 17183946
TI  - [The significance of IL-13 gene +2044G/A mutation in patients with inflammatory
      bowel disease].
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is caused by a combination of
      genetic, immunological and environmental factors. Despite recent advances in the
      study of IBD pathogenesis, including the discovery of the NOD2/CARD15 mutation in
      40% of Crohn's Disease (CD) patients, in most IBD patients no known mutations
      have yet been discovered. The interleukin (IL)-13 gene is located near the IBD5
      locus on chromosome 5q31, known to be in linkage disequilibrium with CD. IL-13
      has a role in the pathogenesis of several chronic inflammatory diseases including
      IBD. The +2044G/A mutation, which encodes an IL-13 protein with glutamine instead
      of arginine, has been associated with various inflammatory conditions. However,
      its role in IBD has not been defined. AIM: This is a study of the role of the IL
      13 gene +2044G/A mutation in the susceptibility to and phenotype of IBD. METHODS:
      Two hundred and eighty-five patients with CD and 111 cases of ulcerative colitis
      (UC) were enrolled in the study. Mutation frequency was determined using
      restriction fragment length polymorphism study in IBD patients and 178 healthy
      ethnically matched controls. The mutated allele frequency was determined in
      various clinical sub-groups of IBD patients. Statistical significance of the
      differences in allele frequency in CD and UC patients and healthy controls was
      determined. RESULTS: The +2044G/A allele frequency was similar in CD, UC and
      healthy controls (23.3%, 19.4%, 19.6%, respectively, p = 0.294). There was no
      significant association of +2044G/A mutation carriage with specific phenotypes of
      CD and UC. CONCLUSION: The IL-13 gene +2044G/A mutation has no significant role
      in susceptibility to and phenotype of IBD.

PMID- 17183947
TI  - [The prognostic value of CA 19-9 in the preoperative work-up of pancreatic cancer
      patients].
AB  - Carbohydrate antigen (CA) 19-9 is produced by adenocarcinomas of the pancreas,
      stomach, gall bladder, colon, ovary and lung. Serum CA 19-9 is considered the
      most sensitive marker for pancreatic cancer, being elevated in 75% or more of
      patients with pancreatic cancer. In all three cases of pancreatic cancer
      presented, patients died of their disease quite shortly after diagnosis.
      Preoperative imaging was unsuccessful in exposing the actual advanced state
      extent of the disease and even during surgery its real extent was underestimated.
      The only prognostic indicator of the observed rapid disease progression was a
      very significant elevation of preoperative serum CA 19-9.

PMID- 17183948
TI  - [ERCP for benign disease in the elderly: a good prognosis].
AB  - BACKGROUND: biliary disease in the elderly (over 80) are common and can be a
      diagnostic and therapeutic challenge. METHODS: medical records of patients age 80
      and older who underwent endoscopic retrograde cholangiopancreatography (ERCP) for
      benign biliary disease from January 2000 to April 2005 were studied
      retrospectively. RESULTS: 100 patients of whom data was obtainable underwent 133
      procedures. The indications for the procedure included suspicion of common bile
      duct stones (94.4%), biliary stend insertion and replacement (4%), non-malignant
      obstructive jaundice (0.8%) and echinococcal cyst (0.9%). Midaozolam (100%) and
      fentanyl (100%) were used for conscious sedation. Patient tolerance was good in
      100% of procedures. Therapeutic procedures (endoscopic sphincterotomy, stent
      insertion or replacement) were indicated in 88% of procedures, and successful in
      96.8% of cases. Short term complications (up to 30 days after procedure) occurred
      in 4/5% of ERCP procedures. There was no early mortality. CONCLUSIONS: ERCP is a
      safe procedure in the elderly with a low complication rate and good therapeutic
      efficacy.

PMID- 17183949
TI  - [Clinical and communication simulation workshop for fellows in gastroenterology:
      the trainees' perspective].
AB  - BACKGROUND: The continuing development in computer-based medical simulators
      provides an ideal platform for simulator-assisted training programs for medical
      trainees. Computer-based endoscopic simulators provide a virtual reality
      environment for training endoscopic procedures. This study illustrates the use of
      a comprehensive training model combining the use of endoscopic simulators with
      simulated (actor) patients (SP). AIM: To evaluate the effectiveness of a
      comprehensive simulation workshop from the trainee perspective. METHODS: Four
      case studies were developed with emphasis on communication skills. Three
      workshops with 10 fellows in each were conducted. During each workshop the
      trainees spent half of the time in SP case studies and the remaining half working
      with computerized endoscopic simulators with continuous guidance by an expert
      endoscopist. Questionnaires were completed by the fellows at the end of the
      workshop. RESULTS: Seventy percent of the fellows felt that the endoscopic
      simulator was close or very close to reality for gastroscopy and 63% for
      colonoscopy. Eighty eight percent thought the close guidance was important for
      the learning process with the simulator. Eighty percent felt that the case
      studies were an important learning experience for risk management. CONCLUSION:
      Further evaluation of multi-modality simulation workshops in gastroenterologist
      training is needed to identify how best to incorporate this form of instruction
      into training for gastroenterologists.

PMID- 17183950
TI  - [Open access colonoscopy: do primary care physicians use it properly?].
AB  - BACKGROUND: Open access endoscopy facilitates the performance of colonoscopy on a
      physician's request, without a prior consultation with a gastroenterologist.
      OBJECTIVES: To investigate: (1) the rates of relevant endoscopic findings in
      patients referred by family physicians compared to other specialists; (2) whether
      there is overuse of open-access colonoscopy in our country where the examination
      is free of charge for the patient; (3) whether a high rate of pre-malignant and
      malignant incidental findings might justify a more liberal approach to the
      indications of colonoscopy. METHODS: Prospective study including all consecutive
      ambulatory patients referred for open access colonoscopy. The indication for the
      examination was tabulated according to the American Society for Gastrointestinal
      Endoscopy (ASGE) guidelines. Endoscopic findings were classified into relevant or
      normal; each relevant finding was correlated with the indication for which the
      examination was performed. RESULTS: A total of 34.2% of patients had a
      colonoscopy performed for an inappropriate indication; family physicians had a
      slightly higher rate of appropriate indications compared with the other
      specialists. However, a relevant endoscopic finding was diagnosed only in 14.0%
      of their referred cases, compared with 22.8% of the other specialists (p =
      0.032). Polyps larger than 5 mm or a malignant tumor were diagnosed in 20.7% of
      the colonoscopies; 19 out of the 83 cases (23%) were diagnosed in examinations
      performed for inappropriate indications. CONCLUSION: It was found that 34% of the
      colonoscopies were performed for inappropriate indications. A higher proportion
      of relevant endoscopic findings was diagnosed among patients referred by
      surgeons, oncologists and internists as compared with those referred by family
      physicians. Considering that as much as 23% of polyps and malignant tumors were
      found in cases performed for inappropriate indications, we suggest that a liberal
      approach to the indications for colonoscopy--probably age over 50 years--may
      benefit the patients.

PMID- 17183951
TI  - [Symptom evaluation as an efficient diagnostic tool for upper abdominal
      diseases].
AB  - INTRODUCTION: GERD and dyspepsia are common conditions, affecting approximately
      25-40% of the general population. In the absence of alarm symptoms, the current
      recommended policy in young dyspeptic patients is a "test and treat" strategy for
      H. pylori. On the other hand, in GERD patients, a therapeutic trial with proton
      pump inhibitors (PPI) is the treatment of choice. AIM: This study aimed to create
      short and simple clinical algorithms, for the diagnosis and treatment of patients
      with upper gastrointestinal complaints. METHODS: Data mining models and
      algorithms (neural networks, decision trees and logistic regression) were used to
      create a diagnostic symptom questionnaire to classify the patients into one of
      two diagnostic groups: GERD vs. non-GERD. The questionnaire was validated against
      endoscopic and clinical diagnoses of 132 patients in a cross-sectional study, and
      was designed to yield a "GERD score". The clinical and economical benefits of the
      new algorithm were evaluated in primary care clinics in Israel. RESULTS: The
      symptoms chosen for the diagnostic questionnaire were heartburn, acid
      regurgitation, sour oral taste, aggravation of symptoms after heavy meals, relief
      of symptoms by antacids, and nocturnal reflux. The use of the algorithm by
      primary care physicians improved clinical outcomes and reduced health resources
      consumption. CONCLUSIONS: This new short algorithm was found to be useful and
      easy to apply in clinical practice. The questionnaire can be also implemented in
      computerized medical systems.

PMID- 17183952
TI  - [The contribution of capsule endoscopy to the diagnosis of small-bowel tumors in
      cases of obscure overt gastrointestinal bleeding].
AB  - BACKGROUND: The source of obscure bleeding is usually located in the small bowel.
      The use of capsule endoscopy (CE) has changed the management of these patients.
      GOALS: To review our experience with the diagnosis of small bowel tumors by CE in
      patients with obscure overt gastrointestinal bleeding. METHODS: Retrospective
      analysis of CE examinations performed consecutively in two university-affiliated
      hospitals. RESULTS: Among 156 patients who underwent CE examination (including 58
      patients with obscure overt bleeding), five patients, all of whom presented with
      melena, were diagnosed as having a small bowel tumor. Three tumors were found in
      one patient (two ileal carcinoids and one ileal benign stromal tumor). A jejunal
      benign stromal tumor was diagnosed in two other patients by push enteroscopy. One
      of these was missed by a subsequent capsule endoscopy examination, and in the
      other, only active bleeding was detected by prior capsule endoscopy. In two
      patients, three small tumors were detected, beyond the reach of push enteroscopy,
      but surgical confirmation was not available. No tumors were found among patients
      in whom the indication for CE examination was not obscure overt bleeding.
      CONCLUSIONS: The possibility of finding a small bowel tumor emphasizes the role
      of capsule endoscopy in patients with obscure overt gastrointestinal bleeding.
      Push enteroscopy should be performed when capsule endoscopy yields negative or
      only suspicious findings.

PMID- 17183953
TI  - [Hypophosphatemia as a prognostic measure of evaluation].

PMID- 17183954
TI  - [Inflammatory bowel diseases: in search of novel cytokines and genes].
AB  - Inflammatory bowel diseases are chronic idiopathic intestinal disorders that have
      diverse manifestations such as diarrhea, rectal bleeding, abdominal pain, weight
      loss, fever and extraintestinal manifestations. The current concept regarding
      their immunopathogenesis is that, in a genetically susceptible host, an aberrant
      response of the mucosa associated lymphoid tissue (MALT) towards a non-pathogenic
      microorganism, elicits the cascade that culminates in intestinal inflammation. In
      this issue of HAREFUAH, Waterman M & al have screened IBD vs. control population
      in search of a genetic association between IBD and the interleukin 13
      polymorphism 2044+G/A, on chromosome 5. Although they have found no such
      association, the editorial addresses the importance of cytokines and novel genes
      for the understanding of the immunopathogenesis of inflammatory bowel diseases,
      and its treatment.

PMID- 17183955
TI  - [Body weight, nutritional factors and physical activity--their influence on
      prognosis after breast cancer diagnosis].
AB  - Numerous studies have examined the association between body weight, nutritional
      factors, physical activity and the risk for primary breast cancer. Relatively few
      studies, however, have examined the associations between these issues and the
      recurrence of the disease and cure of the primary tumor. Today, three areas of
      focus are actively being researched for breast cancer survivors: body weight,
      diet composition and physical activity with specific emphasis on the risk for
      recurrence, survival and quality of life. Increased body weight or BMI (Body Mass
      Index) at diagnosis was found to be a significant risk factor for recurrent
      disease, decreased survival, or both. Overall obesity has been shown to adversely
      affect prognosis. Appropriate weight control may be particularly beneficial for
      breast cancer survivors. Breast cancer survivors should be encouraged to achieve
      and maintain a healthy weight. Limiting fat intake can reduce the risk of breast
      cancer recurrence. Increasing consumption of vegetables and fruits seems to have
      possible beneficial effects during and after treatments. To date physical
      activity after breast cancer diagnosis has been found to reduce the risk of
      death. The greatest benefit occurred in women who performed the equivalent of
      walking 3-5 hours per week at an average pace. Safe weight loss via increased
      physical activity and healthful food choices should be encouraged for normal,
      overweight or obese breast cancer survivors in order to improve survival and life
      quality.

PMID- 17183956
TI  - [Intra gastric balloon for morbid obesity].
AB  - Obesity has become a severe health problem in the Western world, and is rapidly
      becoming the most common disease of the 21st century. Morbid obesity is resistant
      to treatment and is accompanied by considerable morbidity. Some morbidly obese
      patients do not manage to reduce their weight by diet alone, yet are unsuitable
      or unwilling to undergo bariatric surgery. Lately, a new intragastric bioenteric
      balloonR (BIB) was developed to treat these patients. This article summarizes the
      current knowledge and experience with this balloon, and its advantages and
      disadvantages. There are very few placebo controlled studies regarding the BIB,
      and the results are controversial. One study shows the advantage of using the
      balloon compared with diet alone while another study showed no advantage of the
      balloon compared with a strict diet regimen. Uncontrolled studies show that
      balloon treatment combined with diet and physical activity had favorable results
      achieving both weight reduction and reduction in obesity associated morbidity.
      Those results were maintained a year after the balloon was removed. Mild and
      common side effects included vomiting and heartburn, but the balloon also caused
      severe complications including bowel obstruction, perforation and even death. The
      total rate of severe complications is estimated to be about 3%. We conclude that
      the intragastric balloon may be an appropriate addition to the treatment of
      morbid obesity, but only if combined with a proper diet, physical activity and
      psychological support. Patients should be carefully selected and monitored to
      avoid complications.

PMID- 17183957
TI  - [Cholesterol absorption as a target for the treatment of hypercholesterolemia].
AB  - Hypercholesterolemia is a major risk factor for atherosclerosis. HMG-CoA
      Reductase inhibitors (statins), which block hepatic synthesis of cholesterol, are
      the mainstay of therapy of hypercholesterolemia. Recent trials have demonstrated
      the importance of maintaining very low LDL-cholesterol levels in high-risk
      patients. Such low levels are sometimes hard to reach with statin monotherapy.
      Another source of cholesterol is intestinal absorption of dietary cholesterol and
      bile salts. Recent studies have elucidated the mechanism of intestinal
      cholesterol absorption. Ezetimibe, a specific inhibitor of cholesterol absorption
      can be used as an add-on therapy to statins in order to achieve treatment goals.

PMID- 17183958
TI  - [Brucellosis: clinical presentation, diagnosis, complications and therapeutic
      options].
AB  - Brucellosis is a zoonotic disease that causes systemic symptoms and can involve
      many organs and tissues. The major sources of infection are consumption of
      unpasteurized diary products and occupational contact. Brucella is a small, gram
      negative coccobacillus that grows slowly in vitro. There are four species of
      brucella that are pathogenic for humans; in Israel Brucella melitensis is still
      the most frequent organism. There are several methods to identified the organism
      and make the diagnosis (1) isolation of brucella from blood, tissue specimens,
      body fluids and bone marrow; (2) agglutination test and (3) polymerase chain
      reaction (PCR) that has recently been shown to be a promising tool for the
      diagnosis of acute disease. Involvement of the musculoskeletal system is the most
      common complication of brucellosis, while meningitis and endocarditis are life
      threatening complications. The standard treatment for acute and chronic
      brucellosis is a combination of doxycycline with a second drug such as rifampicin
      or gentamicin, in order to cure, prevent complications and relapse. Although the
      rate of occurrence is ever-decreasing due to vaccination of animals, nonetheless,
      the disease has not been eradicated in Israel. This review focuses on the
      clinical presentation, diagnosis, and mainly on complications of brucellosis and
      the available therapeutic options.

PMID- 17183959
TI  - [Colonoscopy for early detection of colorectal cancer in average-risk
      population].

PMID- 17183960
TI  - [Combination of colonoscopy and fecal occult blood test].

PMID- 17183962
TI  - [Nutrition and physical activity for prevention of cancer].

PMID- 17183961
TI  - [Infliximab in inflammatory bowel diseases--conference summary and suggested
      guidelines].
AB  - Infliximab, the monoclonal anti-tumor necrosis factor-alpha (TNF-alpha)
      antibodies preparation, is efficacious in the treatment of inflammatory bowel
      diseases. However, the optimal therapeutic approach is still under investigation.
      Reports on side effects and potential complications of infliximab therapy, as
      well as of other anti-TNF-alpha blocking agents are accumulating. Hence, the
      Israeli Gastroenterological Association had initiated a conference in order to
      discuss the frequent clinical issues that have arisen following the use of
      infliximab for the treatment of inflammatory bowel diseases. The aim was to
      report on the published clinical experience and problems regarding several
      practical aspects of the use of Infliximab, to suggest guidelines that are
      evidence-based and to discuss them with experienced IBD-oriented
      gastroenterologists. The subjects that were discussed include: (1) treatment
      protocols; (2) maintenance therapy in Crohn's disease; (3) prevention of
      infections and (4) therapeutic potential in ulcerative colitis. These topics
      reflect everyday issues that gastroenterologists deal with while treating
      inflammatory bowel disease patients. The manuscript summarizes the literature and
      evidence that were presented in the conference, the points raised at the
      discussions as well as guidelines suggested by work groups that were established
      for each subject. These guidelines may assist and direct the gastroenterologist
      treating inflammatory bowel disease patients with infliximab.

PMID- 17183963
TI  - [Cranberries for preventing urinary tract infections?].

PMID- 17183964
TI  - [The Fuhrman grading system for kidney cancer prognosis].

PMID- 17183965
TI  - [Anatomical basis for perineal pain].

PMID- 17183966
TI  - [Clinical interest in the correlation of phenotype/genotype for the management of
      upper urinary tract cancer].

PMID- 17183967
TI  - [Primary amyloidosis of the bladder. A rare cause of macroscopic hematuria].

PMID- 17183968
TI  - [Botulinum toxin in urology].

PMID- 17183969
TI  - [The writing of the operative report].

PMID- 17183970
TI  - Cerebral venous thrombosis: recent advances and need for an Asian registry.

PMID- 17183971
TI  - Incidence and epidemiology of cerebral venous thrombosis.
AB  - Cerebral venous sinus thrombosis is a disorder whose epidemiology has changed
      over the past few decades. It is no longer regarded as a uniformly fatal disease.
      CVST is not a rare disorder. It may have a differential geographic distribution
      with a higher incidence in the Asian world. It is a disease of neonates, younger
      women and men, often a hypercoagulable state, either acquired (e.g., cancer) or a
      genetic prothrombotic condition may be present. Outcome is not uniformly dismal
      and prognostic criteria that detect patients with a poor outcome have become
      available from prospective studies. There is a paucity of well designed large
      scale epidemiologic studies focused on venous thrombosis from regions where it is
      relatively frequent (South Asia, Middle East). The newer epidemiologic data
      derived from a Caucasian database; suggest a better overall prognosis, younger
      age at distribution than arterial stroke.

PMID- 17183972
TI  - Genetics of cerebral venous thrombosis.
AB  - Cerebral venous thrombosis (CVT) is rare compared to arterial causes of stroke.
      It is often encountered in young patients and may occur in children and neonates.
      Predisposition to CVT also has a genetic basis and inherited thrombophilias are
      known to cause 22.4% of the CVT cases. Inherited thrombophilias should be
      suspected if a patient has recurrent CVT, is less than 45 years age, has a family
      history of venous thrombosis or has no apparent acquired risk factor. Factor V
      Leiden (FVL) is the most common genetic risk factor, followed by the prothrombin
      gene mutation G20210A. Other less common inherited venous thrombophilias include
      deficiencies of Protein S, Protein C and antithrombin III. FVL, the G20210A
      prothrombin gene mutation and a deficiency of protein S and C, cause a reduction
      in the control of thrombin generation. Deficiency of antithrombin causes a
      decreased neutralization of thrombin. Both these mechanisms are responsible for
      venous thrombosis. Inherited thrombophilias with concomitant acquired risk
      factors like surgery, trauma, prolonged immobilization, pregnancy and puerperium,
      oral contraceptives, antiphospholipid antibodies and hyperhomocysteinemia may
      increase the risk of CVT manifold. Similarly the co-inheritance of two or more
      known mutations also increases the risk markedly. FVL, prothrombin G20210A
      mutation, increased factor VIIIc, protein C & S deficiency and antithrombin III
      deficiency have all been reported to cause neonatal stroke due to CVT. Maternal
      and foetal testing is suggested when CVT occurs in neonates.

PMID- 17183973
TI  - Obstetric cerebral venous thrombosis.
AB  - Pregnancy and puerperium are most prevalent prothrombotic states leading to
      cerebral venous thrombosis. Likelihood of stroke to be of venous origin is
      greater in stroke associated with pregnancy compared to stroke unrelated to
      pregnancy. Pregnancy induces several changes in coagulation system, which
      persists at least during early puerperium, rendering it a prothrombotic state.
      Hypercoaguability worsens further after delivery as a result of volume depletion
      and trauma. During puerperium additional risk factors include infection and
      instrumental delivery or Caesarean section. The management follows general rules
      as for the venous thrombosis unrelated to pregnancy, however the prognosis is
      different.

PMID- 17183974
TI  - Infection related cerebral venous thrombosis.
AB  - The incidence of cerebral venous thrombosis (CVT) has dropped dramatically in
      recent years. In the past, before the introduction of antibiotics, infection was
      the main cause of CVT. But this is no longer true. Recently, the occurance of
      septic CVT is rare, which leads to an increased chance of misdiagnosis and
      treatment delay. Early suspicion and recognition is very crucial to improve
      mortality and morbidity rates of this potentially fatal disease. Intravenous,
      wide spectrum, antibiotics and early surgical drainage of the primary site of
      infection whenever possible are essential. Anticoagulation with intravenous
      heparin infusion and corticosteroids use are of uncertain benefit, although some
      reports have shown some favorable response.

PMID- 17183975
TI  - Haematologic disorders and cerebral venous thrombosis.
AB  - This review focuses on the several coagulation disorders (the so called
      hypercoagulable states) that are associated with cerebral venous thrombosis.
      Hypercoagulable states likely explain the high percentage of cases of cryptogenic
      cerebral infarction in young people. The most common of the hereditary defects
      appear to be deficiency of antithrombin III, protein C or protein S, activated
      protein C resistance and prothrombin 20211A mutation. In a large majority of
      cases activated protein C resistance is due to the presence of factor V Leiden.
      Antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies)
      represent an acquired disorder of coagulation. Rare defects include heparin
      cofactor II (HC II), plasminogen or tissue plasminogen activator deficiency
      (TPA), elevated plasminogen activator inhibitor-1 (PAI-1) and dysfibrinogenemia.
      Hyperhomocystinemia is responsible for both arterial and venous thrombosis. A
      work-up to identify one of the recognizable hypercoagulable states is indicated,
      especially in younger patients with stroke. Laboratory evaluation for
      hypercoagulable states may also often be indicated in those patients who do not
      have other obvious risk factors for their stroke. If from clinical history,
      family history and/or laboratory studies, a patient is felt to have a
      hypercoagulable state, the decision for long term chronic anticoagulation needs
      to be individualized. If a hereditary hypercoagulable state is found, it also may
      be appropriate to recommend screening of other family members.

PMID- 17183976
TI  - Unusual causes of cerebral venous thrombosis.
AB  - Cerebral venous thrombosis is a relatively uncommon condition afflicting mostly
      young adults. Thrombosis of cerebral veins or sinuses results in variable and
      nonspecific clinical features, including headache, lethargy, motor or sensory
      deficits, seizures, neck stiffness and sometimes fever. A multitude of conditions
      have been attributed as risk factors for CVT. The more common conditions include
      hereditary thrombophilia, pregnancy and purperium, postoperative state,
      intracranial and local infections and the use of oral contraceptives. Frequently,
      the cause of CVT is multifactorial, and in less than twenty percent of cases no
      clear risk factor is identified. In this review, we have focused on relatively
      rare and unusual causes of cerebral venous thrombosis. Many of the conditions
      described have very few reported cases and the causal relationship is not well
      established.

PMID- 17183977
TI  - Pathophysiology of cerebral venous thrombosis--an overview.
AB  - Cerebral venous sinus thrombosis is a disorder with a unique pathophysiology
      which needs to be described. A Medline search of all articles detailing
      pathophysiology of CVST was done, using keywords: cerebral venous thrombosis and
      pathophysiology. In addition, major texts were reviewed for additional
      references. The pathophysiology of CVST depends on two interconnected events,
      local signs due to venous infarct, e.g., hemiparesis and global signs due to
      raised ICP from an obstructed venous system--papilloedema and isolated
      intracranial hypertension being one of them. Pathophysiology of CVST is diverse
      and makes it easier to understand the diversity of clinical presentations.

PMID- 17183978
TI  - Mechanism of neuronal injury in cerebral venous thrombosis.
AB  - The impact of CVT on the brain is wide spectrum, ranging from completely normal
      parenchyma to brain oedema and/or haemorrhage. Multiple factors relate to
      neuronal injury in CVT including; dural sinus pressure, increased venous flow
      velocities, collateralization of venous channels, rate of occlusion, development
      of cytotoxic and vasogenic oedema, recanalization and accelerated myelination. It
      is suggested that recanalization of occluded vein, as well as, the presence or
      absence and the efficiency of intracranial venous collaterals, may have an impact
      on the extent of brain tissue damage and hence the prognosis of acute CVT.

PMID- 17183979
TI  - Cerebral venous thrombosis--clinical presentations.
AB  - Cerebral venous thrombosis (CVT) is an under diagnosed condition for acute or
      slowly progressive neurological deficit. CVT is less frequent than arterial
      thrombosis. CVT has a wide spectrum of signs and symptoms, which may evolve
      suddenly or over the weeks. It is clinically challenging and mimics many
      neurological conditions such as, meningitis, encephalopathy, benign intracranial
      hypertension, and stroke. With increasing awareness, CVT cases are now being
      diagnosed more frequently. Newer imaging procedures have led to easier
      recognition of venous sinus thrombosis, offering the opportunity for early
      therapeutic measures. It may be difficult to diagnose it on clinical grounds
      alone. Headache is the most frequent symptom in patients with CVT, present in
      about 80% of cases. Most common pattern of presentation is with a benign
      intracranial hypertension-like syndrome. The prognosis of CVT is worse in elderly
      subjects. The shorter the history the more likely is the presence of focal signs.
      Sixth cranial nerve palsy usually manifests as false localizing sign.
      Subarachnoid haemorrhage (SAH) has been described, as the presenting event with
      CVT. Patients may have seizures that can be recurrent. Cranial nerve syndromes
      are seen with venous sinus thrombosis. Psychiatric disturbances are sometimes the
      presenting symptoms. CVT, an important cause of stroke in puerperium, is
      frequently observed in India. We have seen 6 patients of CVT out of 490 stroke
      registry. Of these 6, four were females and two were males. The mean age among
      females was 27.75 years and among males was 41.5 years. Of the 4 females two were
      postpartum; one was on oral contraceptive and in one Antiphospholipid antibodies
      (APLA) were positive. Amongst two males one had hyperhomocysteinemia and one had
      hyperlipidemia.

PMID- 17183980
TI  - Cerebral venous system anatomy.
AB  - Cerebral venous system can be divided into a superficial and a deep system. The.
      superficial system comprises of sagittal sinuses and cortical veins and these
      drain superficial surfaces of both cerebral hemispheres. The deep system
      comprises of lateral sinus, straight sinus and sigmoid sinus along with draining
      deeper cortical veins. Both these systems mostly drain themselves into internal
      jugular veins. The veins draining the brain do not follow the same course as the
      arteries that supply it. Generally, venous blood drains to the nearest venous
      sinus, except in the case of that draining from the deepest structures, which
      drain to deep veins. These drain, in turn, to the venous sinuses. The superficial
      cerebral veins can be subdivided into three groups. These are interlinked with
      anastomotic veins of Trolard and Labbe. However, the superficial cerebral veins
      are very variable. They drain to the nearest dural sinus. Thus the superolateral
      surface of the hemisphere drains to the superior sagittal sinus while the
      posteroinferior aspect drains to the transverse sinus. The veins of the posterior
      fossa are variable in course and angiographic diagnosis of their occlusion is
      extremely difficult. Blood from the deep white matter of the cerebral hemisphere
      and from the basal ganglia is drained by internal cerebral and basal veins, which
      join to form the great vein of Galen that drains into the straight sinus. With
      the exception of wide variations of basal vein, the deep system is rather
      constant compared to the superficial venous system. Hence their thrombosis is
      easy to recognize.

PMID- 17183981
TI  - Computed tomographic imaging of cerebral venous thrombosis.
AB  - Cerebral venous thrombosis (CVT) is an entity which is not rare and can have
      devastating consequences if not diagnosed and treated in a timely manner.
      Although, the gold standard for diagnosing this entity is a catheter angiogram,
      magnetic resonance venography, by virtue of its non-invasiveness and detailed
      demonstration of the cerebral venous structures, has become the diagnostic
      modality of choice for this entity. However, in a resource-strapped country like
      Pakistan, CT scan remains the primary first (and sometimes the only) diagnostic
      modality used in patients with neurological problems. Therefore, it is important
      to recognize the signs of cerebral venous thrombosis on CT scan in order to
      initiate timely therapy. These CT findings of CVT are discussed in this paper.
      The CT findings of CVT have been divided into direct and indirect findings and
      the same have been described for noncontrast and postcontrast CT scans
      separately. A brief discussion of CT venography, which has come around as a
      promising tool for diagnosing CVT as a result of newer innovations in CT
      technology, is also included here.

PMID- 17183982
TI  - MRI and MRV in cerebral venous thrombosis.
AB  - Although Cerebral venous thrombosis is an uncommon cause of stroke among the
      young, it is being increasingly recognised. A prothrombotic risk factor is
      identified in the majority of the patients. In most instances it is seen in women
      in the post-partum period and those on oral contraceptives. Magnetic Resonance
      Imaging (MRI) has improved our ability to diagnose this condition however the
      variability of radiological and clinical presentation remains a challenge. MR in
      combination with MR venography (MRV) is the single most sensitive diagnostic
      technique. The MR appearance of the thrombus within the dual sinus or cortical
      vein is variable and is largely dependent on its age. The loss of the normal flow
      void on spin echo T2 images is a sensitive parameter. Thrombus on MRV is seen as
      loss of high flow signal from the sinus. Focal parenchymal changes occur in
      approximately 50% of cases and are due to oedema and infarction, with or without
      haemorrhage. Appearances of these lesions too are dependent on their age. Diffuse
      changes of raised intracranial pressure with gyral effacement may also be
      present.

PMID- 17183983
TI  - Cerebral angiography and venography for evaluation of cerebral venous thrombosis.
AB  - Cerebral venous thrombosis is an uncommon, but important cause of stroke due to
      its high morbidity. Though conventional catheter based angiography is becoming
      replaced by newer, noninvasive imaging modalities, it still plays an important
      role in the evaluation of patients with suspected sinus or venous thrombosis.
      Techniques of angiography, normal anatomy and variants, and pathological drainage
      patterns are discussed in reference to thrombosis of the major dural and cortical
      venous structures. Knowledge of the normal drainage patterns of the cerebral
      venous system is essential in interpreting angiographic information obtained in
      the evaluation of patients with suspected cerebral venous thrombosis.

PMID- 17183984
TI  - Paediatric cerebral venous thrombosis.
AB  - Cerebral venous thrombosis (CVT) in children is a multifactorial serious disease.
      It is being increasingly diagnosed, mainly because of more sensitive diagnostic
      procedures and increasing clinical awareness. The clinical manifestations can be
      life-threatening and cause long-term neurological deficits. Thromboembolism in
      children is a multifactorial disorder in which both genetic and acquired risk
      factors play a role. CVT occurs in various clinical settings, including
      infection, dehydration, renal failure, trauma, cancer and haematological disorder
      with multiple risk factors. Clinical manifestations of CSVT are nonspecific and
      may be subtle. Most of the clinical scenarios occur at all ages and the clinician
      should consider this diagnosis in a wide range of acute neurological
      presentations in childhood. CVT can have an extremely variable clinical
      presentation, mode of onset, imaging appearance and outcome. Its prognosis
      remains largely unpredictable. Diffusion and perfusion MRI may play a role in
      detecting venous congestion and CT or MR venography are now the methods of choice
      for investigation of cerebral venous thrombosis. The options for treatment of
      infants and children include standard or low molecular weight heparin for 7-10
      days followed by oral anticoagulants for 3-6 months. Specific treatment with
      anticoagulation is controversial in children, but has been established as
      appropriate therapy in adults. Anticoagulant treatment with heparin is probably
      safe and beneficial for children with sinus thrombosis, even those with
      intracranial haemorrhages.

PMID- 17183985
TI  - Cerebral venous sinus thrombosis in neonates.
AB  - Neonatal Cerebrovenous sinus thrombosis(CVST) is extremely rare, however it is a
      devastating condition and one needs to be aware of this condition to diagnose it.
      The risk factors for CVST are still not properly understood. The largest registry
      for stroke and for neonatal CVST is from the Canadian registry which quotes an
      incidence of 0.6 per 100,000 population per year. No data is present for the
      neonatal CVST in this region. One needs to be aware of this devastating condition
      to manage it timely and appropriately. To date there is no consensus on the role
      of anticoagulant therapy and therefore therapy is largely supportive, however
      individual cases have to be evaluated and treated on merit.

PMID- 17183986
TI  - Thrombolytic therapy in cerebral venous sinus thrombosis.
AB  - The use of thrombolytic agents to rapidly lyse the clot has emerged as a
      therapeutic modality, in concert with interventional neuroradiologic approaches
      to deliver the agent locally at the site of thrombosis. There are no randomized,
      double blind, placebo, controlled trials to support thrombolysis as a first line
      therapy in patients with cerebral venous sinus thrombosis compared to standard
      therapy using anticoagulation with weight based dose adjusted unfractionated
      Heparin. Numerous case reports and a single non randomized trial have shown that
      it is comparatively safe and may rescue patients who are deteriorating despite
      anticoagulation with unfractionated Heparin. Consideration must be given to the
      use of thrombolysis in this group. This is an approach that must be restricted to
      centers with considerable experience in neurointerventional therapy.

PMID- 17183987
TI  - Heparin in the treatment of cerebral venous thrombosis.
AB  - Cerebral venous thrombosis (CVT) is a potentially life-threatening condition
      requiring rapid diagnosis and urgent treatment. Heparin anticoagulation is the
      time-honoured treatment, and is advocated in all cases of CVT, irrespective of
      etiology or presence of haemorrhage. The supportive evidence is largely
      observational; data from randomized placebo-controlled trials shows a
      nonsignificant trend favouring heparin. Current practice is to begin heparin
      (unfractionated or low-molecular weight) immediately on confirmation of the
      diagnosis. Newer antithrombotic agents such as ximelagatran may offer advantages
      over heparin and need to be investigated in the treatment of CVT.

PMID- 17183988
TI  - Role of surgery in cerebral venous sinus thrombosis.
AB  - Cerebral venous sinus thrombosis (CVST) usually is taken care of by medical
      management or neuro-interventional vascular techniques. Some cases of CVST may
      take a malignant course if the intracranial pressure increases excessively. This
      increase in pressure is because of oedema in brain tissue due to impediment in
      venous return and/or intracerebral haemorrhage. Neurosurgical experience has
      shown remarkable recovery in these moribund patients if appropriate surgical
      intervention is done within reasonable time. Emergent decompressive craniotomy or
      other neurosurgical interventions are the only appropriate treatment in these
      malignant forms of CVST to prevent mortality and severe morbidity.

PMID- 17183989
TI  - Complications associated with cerebral venous thrombosis.
AB  - Although CVT is associated with a good outcome in the majority of cases, it may
      be complicated by numerous unique and sometimes rare complications. The purpose
      of this review is to discuss the acute and chronic complications of CVT in
      greater detail. Awareness may lead to a more aggressive approach in those in
      which these complications are anticipated and perhaps avoided. The complications
      of CVT may be temporally divided into those unique to the acute stage and those
      that are associated with the chronic stage of CVT. They are venous infarction and
      haemorrhage, subarachnoid haemorrhage, a rapid progression and pulmonary
      embolism. In the chronic stages of CVT, one may encounter dural AV--fistula,
      progressive psychiatric disease, residual epilepsy and recurrence. Cerebral
      venous sinus thrombosis is associated with unique acute and chronic
      complications, some of them may be avoidable, e.g. pulmonary embolism. The
      chronic complications are rare but are potentially treatable, e.g. dural
      AVFistula nidus obliteration with intervention.

PMID- 17183990
TI  - Prognostic indicators in cerebral venous sinus thrombosis.
AB  - Cerebral venous sinus thrombosis (CVT) can affect all age groups, particularly
      women of childbearing age. Overall prognosis for survival and functional
      independence is better than it was believed. Mortality usually ranges from 6-15%
      and transtentorial herniation is the major cause of death. Approximately 80% of
      patients are functionally independent in the long term. Altered mental status and
      cerebral haemorrhage at presentation are the strongest predictors of death and
      disability. Patients with CVT related to pregnancy and puerperium generally do
      better than patients with other causes. Septic CVT carries a worse prognosis than
      aseptic CVT and of the latter, patients with syndrome of isolated intracranial
      hypertension have a better prognosis than those with focal deficits or
      encephalopathy. Anticoagulation is believed to improve outcome in CVT although
      robust data are lacking. Epilepsy, headaches, visual loss, pyramidal deficits and
      cognitive impairment are some of the long term sequelae. The risk of recurrence
      of CVT is low, particularly after the first 12 months of the first episode.

PMID- 17183991
TI  - Local thrombolytic treatment of cerebral venous thrombosis in three paediatric
      patients.
AB  - There is increasing evidence that local thrombolysis can be used with relative
      safety and efficacy in adults with superior sagittal sinus thrombosis (SSST).
      However, little data is available on the use of local thrombolysis in children
      with SSST. We report three patients who received local thrombolysis for dural
      sinus thrombosis. Two patients received urokinase and one patient received
      urokinase followed by local TPA infusion. Recanalization was achieved in two
      patients.

PMID- 17183992
TI  - Isolated deep venous thrombosis--case series, literature review and long term
      follow up.
AB  - Cerebral Venous Sinus thrombosis may rarely be isolated to a cortical vein or to
      the deep venous system. When the deep venous system is involved, prognosis is
      generally poor. In addition, long term follow up is not reported. We conducted a
      retrospective review of all patients admitted to a major tertiary care center,
      with the diagnosis of isolated deep venous thrombosis. Two patients were
      identified with isolated involvement of the deep venous system, they are reviewed
      in detail with long term follow up. Two young South Asian women in their thirties
      with rapid onset of neurologic signs and symptoms are reported. Even when one
      patient required intubation and mechanical ventilation for stupor, both had
      excellent neurologic recovery. Over 6 years of follow up there has been no
      recurrence. In spite of stupor at presentation, complete recovery is possible
      without long term recurrence.

PMID- 17183993
TI  - Oral contraceptives and cerebral venous thrombosis: case report and a brief
      review of literature.
AB  - Cerebral venous thrombosis remains an important and sometimes an elusive cause of
      strokes. Oral contraceptives seem to have a strong causative association with
      this entity. We describe a case that highlights the importance of asking specific
      questions about oral contraceptive use in patients with strokes due to cerebral
      venous sinus thrombosis, especially, where the cause remains cryptic.

PMID- 17183994
TI  - Incidence and pattern of headache in cerebral venous thrombosis.
AB  - Cerebral venous thrombosis (CVT) is a challenging condition because of the
      variability of clinical presentations. CVT can present at all ages, but is seen
      more in young and middle-aged women. CVT does not necessarily occur only when
      there is an obvious underlying etiology. In almost 30% of cases, the etiology
      cannot be established. CVT can present with an acute thunderclap headache, fever,
      seizures, focal deficits, impaired sensorium, or papilloedema. Headache is known
      to be the most frequently associated initial complaint, and is present in more
      than 80% of patients, but it is not always remembered that headache can be the
      sole presenting complaint of CVT and even when early papilloedema is absent.
      Headache can occur in isolation in up to 5% of CVT cases. There is no
      identifiable, uniform, recognizable pattern of headache in CVT, but this article
      discusses the "Headache Profile" that is seen more commonly in this setting with
      an illustration of one such case where the innocuous headache turned sinister.
      Magnetic resonance imaging with venography is the investigation of choice to
      diagnose CVT; computed tomography alone will miss a significant number of cases.
      One must keep in mind the possibility of CVT in every patient who presents with
      new-onset headache of any type, any severity, and in any location, particularly
      when there is worsening in spite of analgesics. Earlier the diagnosis, earlier
      the treatment, better is the outcome.

PMID- 17183995
TI  - Need for the specialist register in Pakistan.

PMID- 17183996
TI  - Images in spine surgery: vertebral osteomyelitis.

PMID- 17183997
TI  - Rotavirus vaccine--a need of the hour in developing countries.

PMID- 17183998
TI  - Interview with Danny L. Jones, Jr., FACHE, chief executive officer, Independence
      Regional Health Center and the Medical Center of Independence.

PMID- 17183999
TI  - Unintended consequences: getting the most while avoiding the worst.

PMID- 17184000
TI  - Leadership.

PMID- 17184001
TI  - Return on investment in pay for performance: a diabetes case study.
AB  - With purchasers' increasing frustration with healthcare costs, more innovative
      approaches to performance-based reimbursement are in demand. Establishing pay-for
      performance programs has become a popular strategy for reorienting payments from
      rewarding volume to rewarding adherence to performance measures. However, while
      performance on quality measures has improved, no reports exist about the return
      on investment (ROI) of pay-for-performance programs. This article compares the
      overall costs of implementing and maintaining a pay-for-performance program with
      the resulting cost trend savings for diabetes care for a health maintenance
      organization's (HMO's) population. The program was a five-year partnership (2000
      2004) between a health plan and an independent practice association (IPA) for the
      HMO product. It reported performance scores on quality, patient satisfaction, and
      practitioner efficiency at the individual physician level. Physician performance
      reporting began in 1999, and payment for that performance began in 2002. The cost
      of the program was 1,150,000 dollars yearly. Savings for diabetes alone in 2003,
      the first post-intervention year, were 1,894,471dollars. Second-year (2004)
      savings against the two-year rolling trend were 2,923,761 dollars. For 2003, the
      resulting ROI was 1.6:1, and for 2004, it was 2.5:1. To our knowledge, this
      article is the first report of a positive ROI for an HMO-based pay-for
      performance program, and it begins to answer the question of whether the
      investment in such programs is worth the effort.

PMID- 17184002
TI  - Hospital governing boards: a study of their effectiveness in relation to
      organizational performance.
AB  - This article describes the development and evolution of governing boards and
      summarizes critical findings from a research study on hospital governing boards.
      The purpose of the research was to examine factors that measure performance of
      governing boards and the relationship of governing board effectiveness to the
      organizational performance of hospitals. Board leaders from 64 nonprofit
      hospitals across the country were surveyed using the BSAQ tool, which measures
      board effectiveness in six areas of competency. Board competency scores of this
      group were compared with those of a previous group, which consisted of more than
      300 nonprofit boards, and demonstrated significantly higher scores. A factor
      analysis conducted to compare the six competency factors between study groups
      revealed a strong single factor in this study. The factors that measure governing
      board performance were found to be consolidated into one single factor of
      collaborative board functioning consistent with emerging governance theory. This
      may support the concept of the importance of governing boards as collaborative,
      socially dynamic networks of leaders. The hospital performance was assessed using
      data from the nationally recognized program, Solucient's 100 Top Hospitals. The
      results demonstrate that higher performing boards did have better hospital
      performance in several dimensions, most notably in profitability and lower
      expenses. Lower expenses were related to higher scores for the BSAQ total score.
      Hospital profitability was positively correlated with all seven BSAQ scores. A
      more favorable Solucient ranking was related to hospitals that had a lower BSAQ
      political score. This was also found in a multiple regression model that
      predicted a favorable ranking when the BSAQ political score was lower. This may
      mean that these boards do what needs to be done to maintain excellent performance
      and do not let politics get in the way of their work. Although governance and its
      effect on hospital performance is a complex concept to study, this investigation
      yields findings of interest to leaders in the healthcare field.

PMID- 17184003
TI  - Is anybody managing the store? National trends in hospital performance.
AB  - Nine standardized measures compiled from Medicare data show trends in the safety,
      quality, financial management, and efficiency for more than 2,500 community
      hospitals over five years ending in 2003. Although much public attention has been
      given to hospital performance, along with exhortations to improve, few measures
      show substantial positive trends, either in variance reduction or overall
      improvement. The authors conclude that environmental forces are not stimulating
      improvement and that the overall picture is one of randomness rather than
      management.

PMID- 17184004
TI  - Establishing and sustaining healthcare operations in a contingency: a logistical
      perspective.

PMID- 17184005
TI  - [Presbycusis: neural degeneration and aging on the auditory receptor of C57/BL6J
      mice].
AB  - Presbycusis is a progressive hearing impairment associated with aging,
      characterized by hearing loss and a degeneration of cochlear structures. In this
      paper we analyze the effects of aging on the auditory system of C57/BL6J mice,
      with electrophysiological and morphological studies. With this aim the auditory
      potentials of mice aging 1, 3, 6, 9, 12, 15, 18, 21 and 24 months were recorded,
      and then the morphology of the cochleal were analyzed. Auditory potentials
      revealed an increase in wave latencies, as well as a decrease in their amplitudes
      during aging. Morphological results showed a total Corti's organ degeneration,
      being replaced by a flat epithelial layer, and a total absence of hair cells.

PMID- 17184006
TI  - [Fitting hearing aids in early childhood based on auditory evoked potentials in
      steady states].
AB  - The purpose of the Newborn Hearing Screening Program is to achieve early.
      Identification and appropriate intervention for hearing loss. Hearing aids are
      the most frequent intervention for deafness. Paediatric specific clinical
      protocols for fitting hearing aids always recommend accurate characterisation of
      hearing thresholds in newborns. In this sense, electrophysiological procedures
      are specially indicated in determined hearing sensibility from the first age of
      life since it is an objective and reliable procedure. 20 normal hearing subject
      and 17 hearing loss subjects participated in this study. Auditory Steady State
      Responses (ASSR) were obtained from all of them. Hearing aid fitting was
      established from the electrophysiological responses. Dynamic range, gain,
      compression ratio and maximum output of the hearing aid were obtained from the
      intensity amplitude function of the ASSR. The procedure discussed in this study
      is specially indicated in newborns and very young children in which other test
      are not suitable.

PMID- 17184007
TI  - [Practical aspects regarding endoscopic treatment for epistaxis].
AB  - INTRODUCTION: A prospective study is presented to evaluate some practical and
      financial aspects regarding surgical endoscopic ligation or cauterization of
      sphenopalatine (SP) and anterior ethmoidal (AE) arteries performed to control
      posterior nasal bleeding. PATIENTS AND METHODS: 35 patients admitted at the ENT
      ward between 2004 and 2006 were included in the study, and distributed into two
      groups depending on the protocol applied in each case. Until March 2005 the
      surgery was performed if there was failure or insecurity of the posterior
      packing, and since that date a substitutive surgical protocol (not including
      posterior packing) was applied. RESULTS: 82.9% of the patients were male, with a
      mean age of 55.74 years and a left bleeding in a 60% of the cases.
      Ligature/cauterization was performed on SP in 28 (80%) patients, on AE in 4
      (11.4%), and on both arteries in 3 cases (8.6%). 38.7% of the SP approach only
      one sphenopalatine foramen was observed, through which an only branch of the
      artery passed; 42% of the cases two branches passed through an only foramen, and
      in 19.3% two or more branches were present, breaking into the nose through two or
      more independent clefts. AE was intradural in 3 cases, intranasal attached to the
      cranial base in other 3 and intranasal detached to the cranial base in 1 patient.
      Besides, highly significant differences were found between the two protocols,
      observing a mean reduction of hospital stay of 3.1 days, which throws up savings
      of 939.3 euros per patient. DISCUSSION AND CONCLUSIONS: Surgical treatment for
      epistaxis has proved to be effective (91.2% in our experience) and safe,
      determining an important reduction in hospital stay and avoiding the morbility of
      posterior packing. Accurate knowledge of the anatomy of the arteries implied and
      specific actuation upon the correct bleeding territory are essential to perform
      this surgery.

PMID- 17184008
TI  - [The use of Quality of Life Questionnaire in patients with nasal polyposis].
AB  - OBJECTIVES: Polyposis handicap evaluation through Spanish validation of the
      Rhinosinusitis Disability Index. MATERIAL AND METHODS: Spanish validation of the
      Polyposis Disability Index (PDI). One hundred and fifty one patients referred to
      our Nose Unit in Fundacion Hospital Alcorcon. The Spanish version of the PDI was
      administered after translation and retrotranslation. Internal consistency and
      reliability were established. RESULTS: Spanish adaptation of the PDI and ists
      subscales (functional, emotional and physical) showed a high reliability and
      internal consistency (Cronbach's alfa: 0,90). CONCLUSIONS: Spanish adaptation of
      the PDI is valid, reliable and can be used in a clinical setting to quantify the
      impact of polyposis on patient's quality of life.

PMID- 17184009
TI  - [Management of the nasal base by resecting strips of skin from the columnella].
AB  - The handling of the nasal base includes, changes of inferior lateral cartilages
      and the skin of the nasal base, which vary according to the gendre and race of
      the patient. OBJECTIVE: To propose a technique for the handling of wide nasal
      base in patients with a wide columnella, where reducing its volume allows
      carrying out the alar plasty in a satisfactory way. MATERIAL AND METHODS: 50
      cases of patients with Rhinoseptoplasty, with documented wide base and a wide
      columnella clinically and photographically; reduction of columnella was made by
      resection of two strips of skin at its base. Reducing the thickness of columnella
      and posterior alar plasty. RESULTS: In 100% of the cases that we were managed to
      diminish the nasal base the results were satisfactory. CONCLUSION: The resection
      of strips of skin in the base of the columnella is an effective and fast
      technique to reduce its volume and secondarily reducing the width of the nasal
      base.

PMID- 17184011
TI  - [Epidermoid carcinoma larynx in stage IV].
AB  - OBJECTIVE: To determine the survival, loco-regional control, distant metastases
      and second primary in stage IV laryngeal carcinoma treated by surgery and
      radiotherapy. MATERIAL: Retrospective study of 147 patients treated with surgery
      and radiotherapy with a 5 year minimun follow-up. RESULTS: Overall and cause
      specific survival at 5 and 10 years was 42%, 35% and 49%, 45.8% respectively.
      Loco-regional control was 57.7 % and 54.7% at 5 and 10 years. Local recurrences
      presented in 25.7%, regional recurrences in 74.2%, and distant metastases 10.9%.
      Second primary tumors developed in 12% of the patients, 50% of the cases in the
      lungs. Factors related to survival are evaluated. CONCLUSIONS: In our experience,
      surgery with postoperative radiotherapy in N+, controls 45% of stage IV laryngeal
      carcinoma. Regional recurrencies are the main cause of failure, more frequent in
      N+ patientes, present in the first 36 months after treatment.

PMID- 17184010
TI  - [Diagnosis and treatment of carotid body paragangliomas. Presentation of 9 cases
      and review of the literature].
AB  - Carotid body paragangliomas (CBP) are relatively rare tumors arising from the
      carotid body paraganglion. Clinical signs and images are necessary to establish
      the diagnosis. Surgery is the preferred method of treatment, paying special
      attention to the carotid artery. Nine patients with carotid body tumors were
      identified, three of them with complicated diagnosis. One patient is treated with
      radiotherapy. Out of the eight surgical patients, three preserved the whole
      arterial structure, the external carotid artery is resected in two patients, the
      carotid artery is replaced (safen graft, gore tex prosthesis) in other two
      patients, and the common carotid was tied in the remaining patient. Our objective
      is to show the decisions taken in the patients from our casuistic, comparing them
      to the literature data. We conclude that the diagnosis may be deceptive, and that
      the attitude forward the carotid is variable, always being prepared to do
      arterial replacement techniques.

PMID- 17184012
TI  - [Open rhinolalia, a typical symptom of velo-cardio-facial syndrome].
AB  - The Velocardiofacial (VCF) syndrome is a relatively frequent cromosomopathy that
      usually associates various otorhinolaryngological features, as hipenasal speech,
      typical facies and auricular anomalies. We report a patient with VCF syndrome
      that before being diagnosed had undergone adenoidectomy with a postoperative
      worsening in speech. Otorhinolaryngological clinical features of the VCF syndrome
      are discussed and a diagnostic protocol is proposed to achieve an early diagnosis
      and to prevent iatrogenic interventions in these patients.

PMID- 17184013
TI  - [Unusual cervical cyst. Adenocarcinoma ex-pleomorphic adenoma of a minor salivary
      gland].
AB  - Cysts with an origin in a malignant tumour of the cervical region are rare. It is
      even more uncommon that the malignant tumour has its origin in a minor salivary
      gland as it is the malignant transformation of a pleomorphic adenoma. Some
      considerations are made regarding its localization, histopathology, diagnosis and
      therapeuthic attitude, as well as some advices to take into account in order to
      arrive to the diagnosis and correct treatment in similar cases to the one shown.

PMID- 17184014
TI  - [Effect of smoking withdrawal on hearing loss induced by occupational exposure to
      noise. A preliminary study].
AB  - Smoking and occupational exposure to noise are factors with independent
      predisposition to sensorineural hearing loss. This is a sinergistic and additive
      effect. Nevertheless, we have observed that withdrawal of smoking stops the
      progression on hearing loss in occupational groups with an acoustic exposition
      lesser than 80 dB SPL. Actually, there is not an unique ethiologic hypothesis.

PMID- 17184015
TI  - [Japanese Society of Nephrology's fight against chronic kidney disease:
      initiatives and future directions].

PMID- 17184016
TI  - [CKD Initiative is an important public health problem in Asia and Japan].

PMID- 17184017
TI  - [Global CKD Initiative and the role of Japanese Society of Nephrology].

PMID- 17184018
TI  - [Prevalence and perspectives of CKD in Japan].

PMID- 17184019
TI  - [Challenges to chronic kidney disease in Japan : Japan Association of Chronic
      Kidney Disease Initiative (J-CKDI)].

PMID- 17184020
TI  - [The importance and necessity of CKD guideline].

PMID- 17184021
TI  - [Current strategy for ESRD in Japan].

PMID- 17184022
TI  - [Problems in the medical care for chronic kidney disease in children: action in
      the Japanese Society for Pediatric Nephrology].

PMID- 17184025
TI  - First comes Junior in a baby carriage. Four in 10 kids are now born to unmarried
      moms.

PMID- 17184023
TI  - [Regression of cardiac hypertrophy using angiotensin II receptor blocker in
      patients with chronic kidney diseases].
AB  - OBJECTIVE: Cardiovascular complications proportionally increase as chronic kidney
      diseases (CKD) progress into chronic renal insufficiency or failure. The present
      study addressed whether the long-term use of angiotensin II receptor blocker
      (ARB) exerts a cardio-protective effect in CKD patients with mild to moderate
      renal damage. MATERIAL AND METHODS: Fifteen patients with CKD above stage 3 were
      enrolled in the study. While their previous antihypertensive therapy remained
      unchanged, the ARB candesartan, was newly added to the concurrent therapy and the
      patients were followed for 12-24 months thereafter. RESULTS: The main results
      were as follows: 1) The use of ARB improved the status of BP control
      classifications, shifting them to the better control categories where there was
      less morning hypertension. 2) ARB significantly reduced the left ventricular (LV)
      mass index(LVMI), the relative wall thickness (RWT), the LV intra-dimension in
      diastole(LVIDd), and as a result, the LV ejection fraction(LVEF) improved. In
      parallel, the LV mass category shifted to lower categories, indicating a
      significant improvement. 3) The levels of BNP decreased significantly from 135.2
      +/- 136.0 to 85.0 +/- 80.3 pg/mL. 4) ARB reduced urinary protein excretion in all
      cases. Regardless of an inevitable increase in the serum creatinine(Cr)
      concentration, the slope of reciprocal serum Cr concentration (l/Cr) in the
      treatment period with ARB was significantly less steep compared to that in the
      run-in period. 5) Throughout the observation period, no serious side effects were
      found in any of the patients. CONCLUSION: The present study indicated that the
      long-term use of ARB exerts both cardio-, and renoprotective effects in patients
      with advanced CKD. This agent could be especially indicative and useful not only
      for patients with CKD, but also for patients of CKD with cardiac hypertrophy.

PMID- 17184024
TI  - [A case of arima syndrome (cerebro-oculo-hepato-renal syndrome) in long-term
      survival with hemodialysis].
AB  - We report a long-term survival case of Arima syndrome requiring hemodialysis. The
      patient, now 25 years of age, was hypotonic at birth. She was diagnosed with
      Dandy-Walker syndrome at an early month of age when she underwent posterior
      cranial fossa cystectomy and vermian agenesis was confirmed. With some delay in
      psychomotor development, she showed the development of language comprehension and
      meaningful speech and started to walk without aid at the age of 7 years.
      Polycystic kidneys were found at 11 years, and Arima syndrome was diagnosed at 16
      years when she presented herself to our hospital with rupture of esophageal
      varices. With progressive deterioration of renal function, she was placed on
      chronic hemodialysis at 23 years. She presented short stature, right
      blepharoptosis and telecanthus on physical examination; pancytopenia, liver
      dysfunction and renal failure on laboratory studies agenesis of cerebellar vermis
      on magnetic resonance imaging reduced amplitude of electroretinographic response,
      and retinal pigmentary changes under funduscopy. Hemodialysis was initiated
      uneventfully except that nafamostat mesilate was used as anticoagulant because of
      her bleeding tendency. Arima syndrome, also known as cerebro-oculo-hepato-renal
      syndrome, is a disorder characterized by cerebellar vermis aplasia and other
      clinical features such as profound psychomotor retardation, severe visual
      impairment, characteristic facial appearance with blepharoptosis, hepatic
      fibrosis and progressive renal insufficiency. The clinical findings of our
      patient were consistent with Arima syndrome though her psychomotor retardation
      and visual impairment were relatively moderate as compared with those previously
      reported. As most patients with Arima syndrome may die of uremia in their early
      teens, dialysis therapy should be considered to improve the patient's survival
      and quality of life depending on the severity of psychomotor retardation and
      other systemic disorders.

PMID- 17184026
TI  - A virulent enemy.

PMID- 17184027
TI  - The winds of change.

PMID- 17184028
TI  - Salt--Neptune's poisoned chalice.

PMID- 17184029
TI  - Should doctors be Darwinian?

PMID- 17184030
TI  - Graduate entry to medicine--the way forward.

PMID- 17184031
TI  - Advances in chronic obstructive pulmonary disease.
AB  - COPD is one of the commonest causes of morbidity and mortality in the world and
      is increasing in prevalence. Current therapies are not very effective and no
      current treatment prevents the relentless progression of airflow limitation that
      characterizes this disease. Smoking cessation is the only strategy that reduces
      this decline in lung function and, although bupropion is the most effective aid
      to quitting, more effective treatments of nicotine addition are needed. The
      mainstay of treatment is bronchodilators for symptom relief and inhaled
      anticholinergics and beta2-agonists are useful by reducing hyperinflation of the
      lungs. A new once daily inhaled anticholinergic is the most effective
      bronchodilator, but long-acting inhaled beta2-agonsts are also useful.
      Theophylline is used as an additional bronchodilator in more severe patients and
      may have some anti-inflammatory action. By contrast, inhaled corticosteroids are
      poorly effective and do not reduce disease profession, although recent studies
      with combination inhalers (corticosteroid + long-acting beta2-agonist) have shown
      better effects. Long-term oxygen therapy is needed by patients with pulmonary
      hypertension and right heart failure. There is a pressing need to develop new
      classes of therapy, and several new drugs are currently in development, including
      inteleukin-8 antagonists, phosphodiesterase-4 inhibitors, protease inhibitors and
      antioxidants.

PMID- 17184032
TI  - A journey through your prostate.

PMID- 17184033
TI  - John Coakley Lettsom and the introduction of digitalis into clinical practice at
      the end of the eighteenth century.

PMID- 17184034
TI  - Something old, something new, something borrowed, something blue ...

PMID- 17184035
TI  - The neurosurgery of children.

PMID- 17184036
TI  - Those magnificient men in those flying machines--aviation medicine research at
      Farnborough in World War II.

PMID- 17184037
TI  - The NHS is dead--long live the NHS.

PMID- 17184038
TI  - Healthcare snags Baldriges. National quality awards offer instant notoriety.

PMID- 17184040
TI  - Medicaid panel report in limbo. Commission members cite new Congress' agenda.

PMID- 17184039
TI  - Hospitals' dirty secret. New reports on hospital patient safety and infections
      reveal pattern of deadly and expensive, yet preventable, medical errors.
AB  - They "will be met with skepticism by some, shock by others and incredulity by the
      remainder", says David Nash, left, editor of the American Journal of Medical
      Quality, about three new reports published in the journal that question patient
      safety in the nation's hospitals. The reports use different methods but all come
      to same conclusion: Poor practices at hospitals lead to deadly, costly
      infections.

PMID- 17184041
TI  - HCA's next move? Asset sale possible to cut debt, analyst says.

PMID- 17184042
TI  - Carilion's conversion targeted. Group fears revamp could monopolize market.

PMID- 17184043
TI  - For comparison's sake. Wanted: an agency to put the evidence in evidence-based
      medicine.

PMID- 17184044
TI  - In defense of board service. Healthcare executives can gain valuable skills,
      perspective as for-profit directors.

PMID- 17184045
TI  - Imaging rules changing focus. The CMS' revisions to imaging reimbursements, self
      referrals could give hospitals a leg up on their physician competitors in '07.

PMID- 17184046
TI  - United she stands. SEIU's Henry, called 'a new breed of labor leader', hopes to
      consolidate unions across industries.

PMID- 17184047
TI  - AHA asks IRS for help with IT. Letter requests clarification on anti-kickback
      rules.

PMID- 17184048
TI  - Why we worry about the things we shouldn't...and ignore the things we should.

PMID- 17184049
TI  - The year in medicine from A to Z.

PMID- 17184050
TI  - An African miracle.

PMID- 17184051
TI  - A win-win accounting trick. Forcing the U.S. to get real about health costs in
      one easy step.

PMID- 17184052
TI  - [Current approaches to intraoperative diagnosis and treatment of low cardiac
      output during cardiosurgical operations].
AB  - The paper deals with the development of a diagnostic and therapeutic algorithm of
      intraoperative heart failure during cardiosurgical operations on the basis of
      evaluation of systolic and diastolic functions of the left and right ventricles.
      The study included 101 patients with low cardiac output in the postperfusion
      period. All the patients suffered from coronary heart disease and they underwent
      myocardial revascularizing operations under extracorporeal circulation. In all
      the patients, in addition to traditional hemodynamic parameters (heart rate,
      blood pressure, central venous pressure), the functional status of the left and
      right ventricles was evaluated by transesophageal Doppler echocardiography (TED
      echoCG) and the thermodilution technique using a Swan-Ganz catheter having a
      prompt thermistor. Evaluating the diastolic and diastolic functions of the right
      and left ventricles makes it possible to identify 2 types of left and right
      ventricular failure: 1) that due to systolic dysfunction and 2) that due to
      concomitance of systolic and diastolic dysfunctions. Dobutrex (5-7.5
      microg/kg/min) should be used in right ventricular systolic dysfunction. Amrinone
      (5-10 microg/kg/min) should be given to patients with concomitance of systolic
      and diastolic dysfunction; in this situation, a combination of dobutrex and
      nitroglycerin (100-150 ng/kg/min) may be used. The drugs of choice in impaired
      left ventricular systolic function are epinephrine (30-100 ng/kg/min), dopamine
      (5-10 microg/kg/min), or dobutrex (5-7.5 microg/kg/min). Their combination with
      sodium nitroprusside can enhance the efficiency of therapy. In patients with left
      ventricular failure caused by systolic and diastolic dysfunction, epinephrine,
      dopamine, or dobutrex may be combined with amrinone (5-10 microg/kg/min) or
      nitroglycerin (100-150 ng/kg/min).

PMID- 17184054
TI  - [Use of sevoflurane during cardiosurgical and endovascular operations in
      children].
AB  - The good tolerability of sevoflurane, the mild and prompt onset of a hypnotic
      state, the absence of airway irritation, and the safe use of the agent make the
      anesthetic of choice for introductory anesthesia in pediatric cardiosurgery. The
      purpose of the study was to develop and assess the procedure of sevoflurane
      anesthesia during cardiosurgical and endovascular operations in children with
      congenital heart diseases. Twenty-five children aged 2-9 years (of them 15
      children with congenital heart disease) operated on under extracorporeal
      circulation (EC) were examined. Ten children underwent X-ray surgical
      endovascular interventions: closure of the patent arterial duct with an
      "Amplatzer ductus occluder" system. The duration of operations under EC was 116
      to 289 min; that of EC was 60-20 (49 +/- 8) min. Endovascular operations lasted
      60-80 min. Premedication was made with ketamine, midazolam, and methacin during
      cardiosurgical operations. The children were referred without premedication,
      escorted by their parents for endovascular surgical interventions where in the
      parents' presence the children were given inhalational sevoflurane at a
      concentration of 5-6% through the mask of an anesthetic apparatus until they fell
      asleep. This made it possible to avoid the child's weeping and resistance and to
      puncture the peripheral vein without pain. Steady-state hemodynamics and
      metabolism suggest that combined anesthesia using sevoflurane at a concentration
      of 1.3-22% of the minimal alveolar one is adequate in correcting congenital heart
      disease in children. The application of this anesthetic procedure permitted
      extubation of 73% of children within 1-2 hours when their condition met the
      criteria for early activation and extubation.

PMID- 17184053
TI  - [Anesthesiological provision of surgical correction of dilated cardiomyopathy in
      patients with chronic heart failure].
AB  - When dilated cardiomyopathy (DCM) is surgically corrected, intraoperative
      intracardiac hemodynamic changes and additional ischemia of the disabling
      myocardium make special demands for anesthesia, prevention of cardiovascular
      insufficiency, and maintenance of circulatory oxygen-transporting function
      (COTF). For the development and evaluation of an anesthetic support protocol for
      patients with DCM, clinical parameters, hemodynamics and oxygen transport was
      comprehensively analyzed in 50 DCM patients aged 16-68 years in the
      intraoperative period of surgical correction of myocardial pathology. All the
      patients underwent implantation of an extracardiac mesh framework in combination,
      if required, with correction of mitral insufficiency under extracorporeal
      circulation (EC), drug-induced cold cardioplegia. Analysis of comprehensive
      clinical studies made it possible to provide scientific evidence and to
      successfully use the anesthetic support protocol for correcting operations of
      chronic heart failure in patients with DCM, the basic principles of the support
      being an effective preoperative preparation of a patient to attenuate the signs
      of congestive heart failure; preventive intraaortic balloon contrapulsation
      before surgery; overall monitoring of hemodynamics and oxygen transport; balanced
      use of anesthetic agents in the doses that exert no cardiosuppressive effect;
      preload optimization and postload reduction; the minimum use of catecholamines;
      prevention of arrhythmias; and a reduction in the duration of myocardial
      ischemia.

PMID- 17184055
TI  - [Central hemodynamics, gas exchange, and gas oxygen-transporting function in
      combined anesthesia using xenon during operations under extracorporeal
      circulation].
AB  - The advantages of xenon include its good hemodynamic profile and possible
      cardioprotective properties. The investigation was undertaken to study central
      hemodynamics, lung gas exchange, and blood oxygen-transporting function in xenon
      anesthesia in patients operated on under extracorporeal circulation (EC). Fifteen
      patients aged 41-69 years operated on for coronary heart disease were examined.
      The severity of the patients' baseline status corresponded to NYHA functional
      classes I to IV. The duration of an operation was 251 +/- 10 min; that of EC was
      97 +/- 5 min; aortic ligation lasted 59 +/- 3 min. After induction of anesthesia
      with propofol via concentration-regulated infusion (CRI) and with fentanyl,
      delivery of xenon was initiated at concentrations of 47 +/- 1 to 52.5 +/- 1%,
      which was mixed with oxygen. Propofol CRI was used during EC. After the latter,
      xenon was inhaled at concentrations of 47.7 +/- 1 to 53.3 +/- 1%. The mean
      arterial pressure (BP(mean)), heart rate (HR), and cardiac index (CI) remained
      unchanged during xenon anesthesia in the preperfusion period. After EC during
      xenon anesthesia, CI significantly rose with a moderate increase in HR without
      inotropic support. BP(mean) was moderately, but statistically significantly
      decreased. Prior to and following EC, there were no changes in the values of
      blood oxygen-transporting function.

PMID- 17184056
TI  - [Changes in cerebral circulation in patients with coronary heart disease during
      myocardial revascularizing operations under combined xenon anesthesia].
AB  - Twenty-five patients with coronary heart disease were examined in the
      preperfusion stage of myocardial revascularing operations under extracorporeal
      circulation. All the patients received combined anesthesia with xenon (Xe) as
      minimum flow anesthesia with flow of gases: oxygen, 0.4 l/min; Xe, 0.9 to 0.4
      l/min. Cerebral circulation was investigated by transcranial Doppler study. The
      following parameters of the circulation: maximum systolic and diastolic blood
      flow velocities and pulsatile index were bilaterally estimated, by insonating the
      middle cerebral artery (MCA). When the concentration of Xe was as high as 50-60%,
      systolic and diastolic blood flow velocities along the MCA increase and the
      pulsatile index decreased. Opposite results were obtained 8 minutes after Xe feed
      was stopped. The findings provide evidence that Xe increases cerebral circulation
      and has a significant hypnotic effect. The increased systolic and diastolic blood
      flow velocities with the decreased peripheral resistance index in the MCA suggest
      that Xe diminishes peripheral vascular resistance in the pial arteries of the
      brain.

PMID- 17184057
TI  - [Calculated and measured blood propofol concentrations during target-control
      infusion by means of a Diprifusor system during operations under extracorporeal
      circulation].
AB  - The study was undertaken to compare measured versus calculated propofol
      concentrations (C(m) and C(c), respectively), by using Diprifusor technology in
      cardiac surgery with cardiopulmonary bypass (CPB). The study included 10 NYHA II
      III patients (aged 27-45 years) undergoing mitral valve replacement. Propofol
      (Diprivan PFS 50 ml, AstraZeneca) was target-control infused (TCI) by the
      Diprifusor system (Graseby 3500). C(c) was titrated to maintain the BIS value
      close to 40. Propofol in doses of 2.1 +/- 0.05 mg/kg was required for induction.
      Anesthesia before, during, and after CPB required propofol in doses of 5.4 +/-
      0.3, 3.9 +/- 0.2, and 3.1 +/- 0.2 mg/kg/h, respectively. The doses of fentanyl
      were 4.4 +/- 0.1 microg/kg for induction of anesthesia and 4.5 +/- 0.4, 2.4 +/-
      0.2, and 0.2 +/- 0.1 mg/kg/h for its maintenance before, during, and after CPB,
      respectively. The patients received rocuronium in the standard doses for
      neuromuscular relation. C(m) was determined by high-performance liquid
      chromatography with ultraviolet detection (Agilent 1100, column C18, Altima).
      Blood propofol concentrations were measured at: 1) intubation; 2) skin incision;
      3) sternotomy; 4) aortic cannulation; 5) 30 min of CPB; 6) 60 min of CPB; 7) the
      end of CPB; 8) 30 min following CPB; 9) skin closure; 10) awakening. Data were
      expressed as mean +/- SEM. The values were compared by linear regression.
      Student's t-test was used with p < 0.05. C(m) was 2 times higher than C(c) at all
      stages. A close correlation was found between C(m) and C(c): r = 0.83, p = 0.038.
      It is concluded that Marsh's PK/PD model predicts the trend in blood propofol
      concentrations during uncomplicated operations on the open heart satisfactorily,
      but C(c) was constantly 2 times less than C(m).

PMID- 17184058
TI  - [Comparison of two schemes of administering the Russian protamine sulfate after
      extracorporeal circulation in cardiosurgical patients].
AB  - The paper presents data of a study comparing two schemes (Scheme 1: a
      heparin/protamine ratio of 1:2; Scheme 2: a heparin/protamine ratio of 1:3) for
      administering protamine sulfate to neutralize heparin in patients after
      extracorporeal circulation. A larger dose of protamine sulfate is shown to induce
      significant thrombocytic dysfunction, resulting in increased postoperative
      hemorrhage. To minimize protamine sulfate doses required for neutralization of
      the anticoagulant effect of heparin is a way of preventing these complications.

PMID- 17184059
TI  - [Comparative assessment of the modes of autoblood reservation in patients during
      operations on the heart under extracorporeal circulation].

PMID- 17184060
TI  - [Impressions of a visit to the Berlin Cardiology Center].

PMID- 17184061
TI  - [Use of a Transtec transdermal therapeutic system of buprenorphine for analgesia
      in the early periods after cardiosurgical operations].
AB  - The analgesic effect of a transdermal therapeutic system (TTS) (Transtec) of
      buprenorphine was evaluated for analgesia in cardiosurgical patients in the early
      postoperative period. Before sternotomy, Transtec was applied to the skin of the
      shoulder in 30 patients operated on the heart under extracorporeal circulation. A
      control group comprised 20 patients receiving the nonsteroidal anti-inflammatory
      agent Xifocam in an intravenous dose of 8 mg twice daily. The first injection of
      Xefocam was made 1.5-2 hours prior to tracheal extubation. With the use of
      Transtec, the degree of pain was 1.58 scores by the five-score scale at the
      moment of tracheal extubation; it reduced to 1 score 16 hours after extrubation;
      it was 0.76 scores by the end of the first day, less than 0.5 score by the middle
      of day 2, reduced to zero by the end of day 3. By the moment of tracheal
      extubation, the degree of pain in patients receiving Xefocam was 3 scores; by the
      end of 24 hours, it reduced to 2 scores and remained the same by the end of day
      3. During more effective analgesia with Transtec, inspiratory lung capacity was
      much higher than during that with Xefocam. The difference in the mean values of
      this parameter was 510 to 830 ml (p < 0.05) at the stages of the investigation.
      The findings confirmed a rather long (72-hour) continuous and steady analgesic
      effect of Transtec TTS. Due to the analgesic effect of Transtec, there was a
      significant improvement of respiratory function in patients after cardiothoracic
      operations.

PMID- 17184062
TI  - [Subarachnoidal anesthesia in patients with concomitant diseases of the
      cardiovascular system].
AB  - Age-related changes limit blood circulatory reserves in vital organs, by
      increasing the risk of ischemic and hypoxic lesions. Patients from a peripheral
      vascular surgery department form a high cardiac risk group. Subarachnoidal
      anesthesia is the most optimal anesthetic support (if there are no absolute
      contraindications) during operations for lower extremity varicose veins. Thirty
      patients operated on for this condition were examined to solve the problem
      associated with the effectiveness and safety of this method of anesthesia and to
      define the pattern of hemodynamic rearrangement more precisely. All the patients
      had concomitant cardiovascular diseases, which forced them to be referred to as
      ASA Classes III-IV. The authors monitored basic hemodynamic parameters, such as
      systolic blood pressure (BP), diastolic BP, mean BP (BP(mean)), heart rate, and
      cardiac output, by using a noninvasive procedure by means of a computer equipped
      with a Doppler flowmetric transducer, and ST-segment changes by ECG). The values
      of total and specific peripheral vascular resistance and cardiac index were
      estimated by a calculating method. Analysis of hemodynamic changes revealed no
      significant differences between the groups of elderly and senile patients. On
      examination, all the patients were divided into 2 groups by the type of
      circulation: 1) those with eukinetic circulation and 2) those with hypokinetic
      circulation. Hyperkinetic circulation was not found in the study groups of
      patients. The patients with cardiac disease were observed to have increased
      vascular resistance, in those with hypokinetic circulation, this increase being
      more marked (p < 0.05). In addition, ST-segment had a more stable position in
      patients with hypokinetic circulation. There was a great scatter in ST-segment
      changes in patients with eukinetic circulation in the presence of decreased
      peripheral resistance under preganglionic sympathetic block. With the described
      changes, noteworthy was the stability of BP(mean) values that did not decreased
      below the critical ones. This fact permitted the authors to state that the
      compensatory reserves of the cardiovascular system were preserved under
      subarachnoidal blockade, which in turn suggests the effectiveness and safety of
      the used anesthetic procedure.

PMID- 17184063
TI  - [Impact of combined anesthesia using isoflurane on the development of adaptation
      mechanisms on changing ventilation conditions in thoracic surgery].
AB  - The paper deals with the effect of isoflurane (IF) as a component of combined
      anesthesia during thoracic interventions in the lateral position on the
      development of adaptation mechanisms to a change in artificial ventilation (AV)
      modes--from ventilation of both lungs to that of one lung (unilateral
      ventilation, ULV), long exposure to ULV and to a change from ULV to ventilation
      of both lungs. Eighteen patients at a high operation-anesthetic risk were
      examined. Measurements were made in 6 steps, including conditions in AV, exposure
      to ULV for 15-30, 55-60, and 80-120 minutes, AV after 20-min exposure to ULV, and
      at the end of surgery in the supine position. While analyzing the results, the
      authors made an important observation that IF has a property of preventing
      capillary formation in the ventilated portions, without impairing the mechanism
      of pulmonary hypoxic vasoconstriction in the area of atelectized alveoles. This
      contributed to the optimization of a ventilation-perfusion relationship and
      creates conditions for adequate oxygenation. The use of IF as a component of
      combined anesthesia during thoracic operations associated with a need for
      artificial unilateral ventilation in patients at a high operation-anesthetic risk
      created conditions for optimizing gas exchange and blood circulation at all
      stages of an operation and anesthesia.

PMID- 17184064
TI  - [A ProSeal laryngeal mask as a means of optimizing anesthesiological provision in
      the endoscopy of the trachebronchial tree].

PMID- 17184065
TI  - [Epidural block as a component of anesthesiological provision during abdominal
      operations].
AB  - Two modes of general anesthesia with artificial ventilation in combination with
      epidural block differing in a hypnotic component (inhalational or intravenous)
      were studied in 27 patients. A combination of general and epidural anesthesia
      afforded the best protection from surgical stress during major abdominal
      operations. Inhalational or intravenous anesthetics may be equally used to induce
      unconsciousness. The fact that there may be blood loss is not an absolute
      contraindication to epidural anesthesia. The safety and controllability of
      combined anesthesia increase when its individual components are monitored and the
      protocol is strictly observed. There is a need for further development of
      objective criteria for efficient regional block under general anesthesia.

PMID- 17184066
TI  - [Use of average-acting nondepolarizing myorelaxants in abdominal surgery].
AB  - The efficiency and safety of use of average-acting nondepolarizing myorelaxants,
      such as atracurium, vecuronuim, rocuronium, and cisatracurum, during abdominal
      surgical interventions under general anesthesia (combined or total intravenous
      anesthesia) were investigated in 162 patients. There is evidence that the use of
      the above agents ensures a qualitative myorelaxation during different types of
      operations (laparoscopic and laparotomic) and no impact on hemodynamics
      (according to the data of continuous non-invasive monitoring) allows these
      myorelaxants to be used in patients with concomitant cardiovascular diseases.
      Rocuronium is the myorelaxant of choice for rapid tracheal intubation. The high
      degree of predictability of the duration of an effect produced by atracurium and
      cisatracurium enables these myorelaxants to be used without monitoring
      neuromuscular conduction. With the equally good quality of myoplegia and with
      virtually comparable consumed diseases, the infusion procedure of relaxation
      maintenance is preferable for early activation of patients. Insignificant effects
      on histamine release make it possible to use vecuronium, rocuronium, and
      cisatracurium in patients with the compromised immune system.

PMID- 17184067
TI  - [Clinical experience in using isoflurane, sevoflurane, and total intravenous
      anesthesia during visceral transplantation].
AB  - Based on 256 anesthesias, the authors comparatively studied the results of total
      intravenous anesthesia (TIVA) with neuroleptic analgesics and inhalational low-
      and minimal flow anesthesia with isoflurane in the anesthestic support of major
      operations on the liver. Both sevoflurane and isoflurane may be widely used
      during long and traumatic operations on the liver since the agents are
      distinguished by a low hepatotoxicity, the absence of pharmacological activity of
      their metabolism, a rapid elimination from the body in a virtually unchanged
      form. The use of sevoflurane and isoflurane in the low and minimal flow modes can
      substantially reduce the pharmacological load with opiates and myorelaxants,
      which is particularly important in patients with liver diseases and these modes
      have some advantage over TIVA during which the consumption of myorelaxants and
      neuroleptic analgesics has proved to be significantly higher. The minimal flow
      (0.4-0.5 l/min) mode uses mostly few inhalation anesthetics. The use of
      seroflurane reduces the period of spontaneous breathing recovery to a greater
      extent, activates the patient more rapidly, and substantially reduces the risk of
      iatrogenic complications after long and traumatic operations associated with
      visceral transplantation.

PMID- 17184068
TI  - [Hemodynamic disorders in liver transplantation and their correction].
AB  - To study the pre- and intraoperative causes of hemodynamic disorders at the basic
      stages of liver transplantation in adult recipients, case histories and
      anesthesia protocols were analyzed in detail in 15 recipients of the cadaveric
      liver (Group 1) and 60 recipients of a liver portion taken from a living relative
      donor (Group 2). The patients' preoperative status, the etiology of the disease,
      the pattern and scope of preoperative preparation and examination, the cause of
      anesthesia, the volume, pattern, and rate of infusion were studied. Particular
      emphasis was placed on the presence of pathophysiological prerequisites and
      various intraoperative factors, which are causes of hemodynamic disorders.
      Orthotopic transplantation of the liver was performed under generalized balanced
      anesthesia whose major components were the inhalational anesthetics isoflurane
      and sevoflurane (89.3%) or total intravenous anesthesia based on neuroleptic
      anesthetics (10.7%). The main causes of hemodynamic disorders were the patients'
      severe baseline condition, anemia, ascitis, intoxication, encephalopathy, and the
      specific features of a surgical intervention, blood loss, heavy plasma and
      perspiration losses, water-electrolyte balance impairments, vein-vein shunt and
      reperfusion syndrome. Operations of extraordinary duration (longer than 15-20
      hours) required higher plasma compensation volumes (36-52 ml/kg). Severest
      hemodynamic disorders were observed in patients admitted to hospital for
      emergency transplantation of the cadaveric liver. These patients who are to
      undergo transplantation are outside hospital in most cases, which is why any
      operation should be regarded in them as an emergency one made in patients who are
      in a very severe state (ASA IV-VE).

PMID- 17184069
TI  - [Use of different types of target propofol concentration-control infusion:
      theoretical and practical aspects].
AB  - Examinations were made in 105 patients who had undergone total intravenous
      anesthesia on the basis of the immune circulating components (ICC) of propofol by
      different pharmacokinetic models--Marsh and Schnider, by aiming at plasma or an
      effector zone. Along with good controllability of ICC-anesthesia, with
      theoretical and practical differences of the employed models are shown. The
      capacities of an up-to-date universal perfusor are demonstrated, by using Asena
      PK as an example. Practical recommendations on its application are given. The
      prospects of anesthesia automation are briefly discussed.

PMID- 17184070
TI  - [Artificial therapeutic feeding in the short bowel syndrome].

PMID- 17184072
TI  - [Sevoflurane: properties, use, and prospects].

PMID- 17184073
TI  - [Mechanisms and ways of myocardial preconditioning].

PMID- 17184074
TI  - Multiple bur hole surgery for the treatment of moyamoya disease in children.
AB  - OBJECT: The authors' aim in this study was to review their experience in the use
      of indirect revascularization alone in a series of 14 children with moyamoya
      disease, in which numerous bur holes and arachnoid openings were made over each
      affected hemisphere. METHODS: Revascularization through multiple bur holes and
      arachnoid openings was performed in 14 children (mean age at diagnosis 6.5 years
      [range 3-15 years]) who suffered from progressive moyamoya disease. The authors
      performed surgery in a total of 24 hemispheres during 18 procedures. Ten children
      underwent bilateral multiple bur hole procedures, three underwent a unilateral
      procedure in the more severely affected hemisphere, and one child had previously
      undergone an encephaloduroarteriomyosynangiosis on the contralateral side. Ten to
      24 bur holes were made in the frontotemporoparietooccipital area of each
      hemisphere, depending on the site and extent of the disease. Early postoperative
      perfusion magnetic resonance imaging studies, performed in the five most recent
      cases, showed restoration of cortical perfusion as early as 3 months, which was
      confirmed on subsequent angiography studies (performed between 8 and 12 months
      postoperatively) that showed excellent revascularization of the ischemic brain by
      external carotid artery collateral vessels. None of the children sustained
      further ischemic attacks postoperatively. Motor improvement was noted in those
      who had presented with paresis. A single seizure episode occurred in two patients
      at 2 weeks and 5 months after surgery; both children had presented with epilepsy.
      There were no postoperative deaths, and only one complication (an infected lumbar
      shunt in the patient who required cerebrospinal fluid [CSF] drainage). Five of
      the 18 procedures were complicated by subcutaneous CSF collections, which
      resolved with tapping and compressive head dressings; a transient lumbar drain
      was necessary in one case. CONCLUSIONS: The results obtained in this series
      suggest that in children with moyamoya disease this simple technique is both
      effective and safe. Furthermore, it is effective as a sole treatment without
      supplementary revascularization procedures.

PMID- 17184075
TI  - Incidence and severity of postoperative cerebellar mutism syndrome in children
      with medulloblastoma: a prospective study by the Children's Oncology Group.
AB  - OBJECT: Cerebellar mutism syndrome (CMS) is a unique postoperative syndrome
      typically arising 1 to 2 days after resection of a midline posterior fossa tumor;
      it consists of diminished speech progressing to mutism, emotional lability,
      hypotonia, and ataxia. Most descriptions have been limited to small institutional
      series using a retrospective chart review methodology. METHODS: The authors
      incorporated a CMS questionnaire in two large clinical trials (Children's Cancer
      Group [CCG] 9931, treatment for high-risk medulloblastoma/primitive
      neuroectodermal tumor; and CCG/Pediatric Oncology Group [POG] A9961, treatment
      for average-risk medulloblastoma) to prospectively survey for incidence,
      severity, and possible causes of CMS in children with newly diagnosed
      medulloblastoma. Information pertaining to 450 of the 463 patients enrolled in
      the studies was available for review (82 patients in CCG 9931, and 368 patients
      in CCG/POG A9961). Cerebellar mutism syndrome occurred in 107 (24%) of 450
      children. Symptom intensity was judged to have been severe in 43%, moderate in
      49%, and mild in 8% of these 107 patients. Mutism and ataxia were the features
      most frequently judged as severe. In both cohorts, preoperative brainstem
      invasion was the only feature that correlated with risk of CMS. One year after
      diagnosis, nonmotor speech/language deficits, neurocognitive deficits, and/or
      ataxia persisted in a significant fraction of patients. CONCLUSIONS: Nearly one
      quarter of patients who underwent resection of a medulloblastoma developed
      symptoms of CMS, of which 92% were judged to be of moderate or severe intensity.
      Brainstem invasion by tumor was the only risk factor that correlated positively
      with CMS occurrence; there was a negative correlation with cerebellar hemisphere
      tumor location. As more radical resections are attempted for medulloblastoma, the
      potential for increased morbidity must be carefully weighed against prognostic
      factors, especially in patients with brainstem invasion.

PMID- 17184076
TI  - Collagen nerve guides for surgical repair of brachial plexus birth injury.
AB  - OBJECT: Standard brachial plexus repair techniques often involve autologous nerve
      graft placement and neurotization. However, when performed to treat severe
      injuries, this procedure can sometimes yield poor results. Moreover, harvesting
      the autologous graft is time-consuming and exposes the patient to additional
      surgical risks. To improve surgical outcomes and reduce surgical risks associated
      with autologous nerve graft retrieval and placement, the authors use collagen
      matrix tubes (Neurogen) instead of autologous nerve graft material. METHODS:
      Between 1991 and 2005, the authors surgically treated 65 infants who had suffered
      brachial plexus injury at birth. During this time, seven patients were treated
      using collagen matrix tubes (Neurogen). This study is a retrospective analysis of
      the initial five patients who were treated using the tubes. Two patients
      underwent tube placement recently and were excluded from the analysis because of
      the inadequate follow-up period. Four of the five patients experienced a good
      recovery (motor scale composite [MSC] > 0.6), and three exhibited an excellent
      recovery (MSC > 0.75) at 2 years postoperatively. The MSC improved by an average
      of 69 and 78% at 1 and 2 years, respectively. The movement scores improved to
      greater than or equal to 50% range of motion in most patients, and the
      contractures were usually mild or moderate. Follow-up physical and occupational
      therapy evaluations confirm these patients' functional status. When last seen,
      four of five of these children could feed and dress themselves. CONCLUSIONS:
      Technically, the use of the collagen matrix tubes was straightforward and
      efficient, and there were no complications. The outcomes in this small series are
      encouraging.

PMID- 17184077
TI  - Aquaporin 4 and hydrocephalus.

PMID- 17184078
TI  - Expression of the water-channel protein aquaporin 4 in the H-Tx rat: possible
      compensatory role in spontaneously arrested hydrocephalus.
AB  - OBJECT: Aquaporin (AQP) water channels play an important role in water movement
      in the central nervous system. The authors used an animal model to examine the
      relationship between AQP4 expression and spontaneously arrested hydrocephalus.
      METHODS: . Congenitally hydrocephalic H-Tx (hH-Tx) rats and nonhydrocephalic H-Tx
      (nH-Tx) rats were used in the study. Brain tissue sections were obtained from
      animals in both groups at 1 day, 1 week, 4 weeks, and 8 weeks of age. Sections
      were immunostained using AQP4 antibodies, and AQP4 expression was assessed. In
      the nH-Tx group, no AQP4 expression was seen in 1-day-old rats, and AQP4
      expression was found in astrocytes around capillaries of the cerebral cortex and
      in ependymal cells lining the ventricles in 1-week-old rats. In the 4- and 8-week
      old nH-Tx animals, AQP4 expression was seen in subpial zones of the cortex, on
      foot processes of pericapillary astrocytes, and in periventricular regions. A
      marked increase in cerebral cortical expression of AQP4 was observed at 8 weeks
      in the hH-Tx rats but not in the nH-Tx rats. CONCLUSIONS: The authors hypothesize
      that the differences in cerebral AQP4 expression in the 1-day-old and 1-week-old
      nH-Tx rats compared with the 4- and 8-week-old nH-Tx rats may be related to the
      fact that the cerebrospinal fluid (CSF) circulation of newborns and infants
      differs from that of adults. It is also possible that the increased expression of
      AQP4 seen in the 8-week-old hH-Tx animals was related to the development of
      alternative pathways of CSF circulation, which also may occur in instances of
      spontaneously arrested hydrocephalus.

PMID- 17184079
TI  - Primary disseminated leptomeningeal oligodendroglioma with 1p deletion. Case
      report.
AB  - The authors report the case of a 2-year-old boy with a primary, diffuse
      leptomeningeal oligodendroglioma in which the deletion of chromosome arm lp was
      identified by performing a fluorescence in situ hybridization (FISH) analysis.
      This previously healthy child initially presented with malaise, anorexia, nausea,
      vomiting, and macrocephaly. Imaging studies confirmed the presence of
      hydrocephalus, and a ventriculoperitoneal shunt was placed. The postoperative
      course was complicated by emesis, continued weight loss, and numerous seizurelike
      episodes. A contrast-enhanced magnetic resonance imaging study performed
      approximately 10 weeks postoperatively showed diffuse leptomeningeal thickening
      and enhancement without evidence of an intraparenchymal mass lesion. A right
      frontal lobe brain biopsy revealed a hypercellular proliferation of small
      oligodendroglioma-like cells, which occupied the leptomeninges diffusely and
      spared the underlying cortical gray matter. The tumor cells displayed prominent
      perinuclear clearing and had evenly spaced, uniformly round nuclei. Occasional
      mitotic figures were observed. Background vessels were thin and delicate, and
      there was no evidence of necrosis. The tumor cells showed strong immunoreactivity
      for S100 protein; the results of immunohistochemical staining were negative for
      glial fibrillary acidic protein, vimentin, epithelial membrane antigen, NeuN, and
      synaptophysin. The deletion of lp was demonstrated by FISH analysis; lq, 19p, and
      19q were intact. This appears to be the first reported case of a primary diffuse
      leptomeningeal oligodendroglioma in which a lp deletion was identified.

PMID- 17184080
TI  - Neuroimaging and pathological findings in a child with cerebral sparganosis. Case
      report.
AB  - The authors report the case of a 6-year-old boy with cerebral sparganosis due to
      infection with a plerocercoid tapeworm larva of Spirometra mansoni. Magnetic
      resonance imaging revealed an area of irregular long T2 signal in the right
      frontal lobe. When compared with images obtained 2 years earlier, the lesion
      appeared to have migrated into the parietal lobe. During surgery for the removal
      of a granuloma, the parasite was discovered and excised. Following surgery, the
      patient's neurological deficits markedly improved. The authors review the
      pathological and imaging features of cerebral sparganosis.

PMID- 17184081
TI  - Congenital glioblastoma multiforme. Case report and review of the literature.
AB  - Congenital intracranial tumors are rare. If such a lesion is detected before
      birth, it is usually an incidental finding on fetal ultrasonography. The
      definition of a "congenital" tumor is controversial. The authors report the case
      of a "definite" congenital glioblastoma multiforme (GBM) diagnosed with the aid
      of ultrasonography and fetal magnetic resonance (MR) imaging in the 37th week of
      gestation. Postnatal MR imaging revealed a massive tumor occupying the patient's
      left temporoparietooccipital area. Angiography was performed to assess
      vascularity and embolize the main feeding arteries. Surgery was performed, and
      the tumor was successfully excised completely. The histopathological diagnosis of
      the tumor was GBM. An examination of the tumor cells revealed no p53
      accumulation, a high MIB-1 index (87.5%), and no staining for epidermal growth
      factor receptor (EGFR). Adjuvant chemotherapy was administered, and the patient
      is doing well at 23 months of age. Congenital GBM should be considered in the
      differential diagnosis in cases in which a fetal ultrasonography study or fetal
      MR image reveals a tumor, especially in the presence of intratumoral hemorrhage.
      Radical tumor removal, administration of adjuvant therapy, and biological
      findings (such as a lack of the overexpression of p53 and EGFR in the tumor
      cells) all point to a longer survival time.

PMID- 17184082
TI  - Purely cystic form of choroid plexus papilloma with acute hydrocephalus in an
      infant. Case report.
AB  - Infants with acute hydrocephalus often present with nonspecific neurological
      signs, and cystic choroid plexus papilloma (CPP) is a very rare cause of acute
      obstructive hydrocephalus. The authors present the case of a 1-year-old girl who
      became irritable, started vomiting, and became comatose within a day. Magnetic
      resonance (MR) imaging revealed a cystic lesion in the third ventricle as well as
      hydrocephalus. Although the aqueduct appeared to be patent, phase-contrast MR
      imaging showed no pulsatile flow of cerebrospinal fluid in the ventricles. An
      emergent endoscopic third ventriculostomy was performed. Endoscopic examination
      revealed a highly mobile cyst attached by a pedicle to the choroid plexus
      adjacent to the Monro foramen in the lateral ventricle. The cyst was totally
      excised during the endoscopic procedure and was subsequently diagnosed as a CPP
      on the basis of histopathological findings. Purely cystic CPP is a very rare
      pathological entity; however, when it does occur, it can cause obstructive
      hydrocephalus which, without rapid diagnosis and surgical intervention, could
      lead to sudden death.

PMID- 17184083
TI  - Synchronous endoscopy and microsurgery: a novel strategy to approach complex
      ventricular lesions. Report of three cases.
AB  - Simultaneous endoscopic and microsurgical (synchronous) approaches represent a
      new paradigm in the treatment of complex ventricular lesions. This technique is
      well suited for lesions that involve multiple ventricular or cisternal
      compartments, have a nonlinear axis, or adhere to critical anatomical or
      neurovascular structures. Two distinct operative corridors, one endoscopic and
      the other microsurgical, are used during synchronous approaches to address such
      lesions, increasing the likelihood of a safe and complete resection. The authors
      present the cases of two children and an adult treated via synchronous
      approaches. All patients had multi-compartmental lesions involving the ventricles
      and/or cisterns. One patient presented with a suprasellar Rathke cyst with a
      significant third ventricular component, one with a hypothalamic hamartoma having
      a substantial cisternal component, and the remaining patient with a choroid
      plexus papilloma in the left lateral ventricle that extended from midbody to the
      temporal horn. In the cases of the Rathke cyst and the hamartoma, debulking in
      the third ventricle and controlled detachment of the lesion from the hypothalamus
      were undertaken using endoscopy, and simultaneous resection of the suprasellar
      component was performed through a subfrontal craniotomy. In the case of the
      choroid plexus papilloma, selective cautery of the choroidal feeding vessels and
      detachment from the temporal tela choroidea were performed using endoscopy, and
      the tumor from the ventricular body to the atrium was resected via a craniotomy.
      In each case the resection concluded with the intersection of endoscopic and
      microsurgical fields. All three patients had good outcomes. Endoscopic and
      microsurgical approaches can be used concurrently to treat multicompartment
      ventricular and/or cisternal lesions with good results. The probable advantages
      of this method are more complete resection and improved safety.

PMID- 17184084
TI  - Vertebra plana due to an aneurysmal bone cyst of the lumbar spine. Case report
      and review of the literature.
AB  - Aneurysmal bone cysts (ABCs) are benign, highly vascular osseous lesions
      characterized by cystic, blood-filled spaces surrounded by thin perimeters of
      expanded bone. Children and young adults are most often affected by spinal ABCs;
      more than 75% of patients are younger than 20 years old at presentation. Although
      ABCs have been documented in all areas of the axial and appendicular skeleton,
      ABCs of the spine present unique challenges due to the risk of vertebral
      destabilization, pathological fracture and vertebral body (VB) collapse, and
      neurological compromise. The authors describe the case of an 8-year-old child who
      presented with low-back pain and was subsequently found to have a lumbar ABC
      causing vertebra plana of the L-3 VB. They also review the literature on ABCs of
      the spine. This case highlights the importance of considering an ABC in the
      differential diagnosis when vertebra plana is seen in pediatric patients.

PMID- 17184085
TI  - Isolated cervical depressed laminar fracture in a child. Case report and review
      of the literature.
AB  - The author reports the case of a child who presented with an unusual C-5
      depressed laminar fracture. The characteristics of the fracture, the mechanism of
      injury, and the treatment are described. Previously published cases are reviewed.

PMID- 17184086
TI  - Epidural venous engorgement resulting in progressive cervical myelopathy from
      shunt-related intracranial hypotension. Case report and review of the literature.
AB  - The authors report an unusual case of engorged epidural veins causing progressive
      cervical myelopathy after long-term cerebrospinal fluid (CSF) shunt therapy and
      intracranial hypotension. An 18-year-old woman, who had previously undergone
      shunt placement with a distal slit valve for a porencephalic cyst when 2 years of
      age, presented with progressive spastic quadriparesis, numbness, and gait
      difficulty. Postural headaches were absent and a lumbar puncture revealed low CSF
      pressure. Neuroimaging disclosed markedly engorged anterior epidural veins
      causing compression of the cervical spinal cord. The slit-valve shunt system was
      surgically removed and an external drain was placed. The patient's CSF pressure
      was gradually raised to clinically tolerable levels. Once the optimal pressure
      was identified, a programmable shunt was placed with the valve set at the same
      level. The patient's neurological status improved, and the epidural veins had
      returned to their normal size on follow-up imaging. The authors describe the
      unique treatment strategy used in this patient and review the literature on
      epidural venous engorgement as it relates to intracranial hypotension.

PMID- 17184087
TI  - Incomplete Currarino triad as an embryological variant. Case report and review of
      the literature.
AB  - Currarino triad is a rare embryological complex of congenital caudal anomalies,
      including anorectal malformation, sacral osseous defect, and presacral mass, that
      results from abnormal separation of the neuroectoderm from the endoderm. The
      authors present an unusual case of a patient who had, in addition to the classic
      features of this syndrome, holocord syringomyelia, low conus medullaris, and
      tethered cord demonstrated by magnetic resonance imaging. They also discuss the
      embryological significance of this clinical entity and briefly review the
      relevant literature.

PMID- 17184088
TI  - Spinal cord pilocytic astrocytoma with leptomeningeal dissemination to the brain.
      Case report and review of the literature.
AB  - Leptomeningeal dissemination of low-grade spinal cord gliomas is an uncommon
      event. The authors report a unique case of leptomeningeal dissemination of a
      spinal cord pilocytic astrocytoma (PCA) to the intracranial cerebral subarachnoid
      spaces in a child. A 2-year-old boy presented with a loss of balance and the
      inability to walk or stand. An intradural intramedullary spinal cord tumor was
      identified, and the lesion was subtotally resected and diagnosed by the pathology
      department to be a PCA. Subsequently, the patient had recurrences of the
      intradural intramedullary tumor at 6 months and 2 years after his original
      presentation. He underwent a repeated resection of the recurrent tumor and
      fenestration of an associated syrinx on both occasions. The pathological
      characteristics of the reresected tumor remained consistent with those of a PCA.
      Postoperative imaging after his last surgery revealed diffuse intracranial
      leptomeningeal dissemination into the cisternal space surrounding the midbrain,
      the suprasellar region, and the internal auditory canal, as well as nodular
      subarachnoid disease in the upper cervical region. The patient then underwent
      chemotherapy, and total spine magnetic resonance (MR) imaging 2 months later
      demonstrated stability in the size of the spinal cord tumor and a decrease in the
      associated syrinx. However, an MR image of the head demonstrated two new areas of
      supratentorial subarachnoid leptomeningeal spread of the primary spinal cord
      tumor at the 2-month follow-up examination. At the 6-month follow-up examination,
      MR imaging of the head and spine demonstrated stable metastatic disease. This
      case illustrates a unique instance of supratentorial leptomeningeal dissemination
      of an intramedullary spinal cord PCA in a child.

PMID- 17184089
TI  - In memorial: Dr. Fred Epstein.

PMID- 17184090
TI  - When opioid analgesia kills.

PMID- 17184091
TI  - [Diabetes, a public health problem. The epidemiology of sugar diabetes and its
      long term complications].

PMID- 17184092
TI  - [Screening and prevention of diabetes].

PMID- 17184093
TI  - [Nutritional approach to diabetes].

PMID- 17184094
TI  - [Pharmacologic treatment of diabetes].

PMID- 17184096
TI  - [What do you know about the measurement of blood sugar?].

PMID- 17184097
TI  - [Tool box].

PMID- 17184095
TI  - [Hypoglycemia: a preventable imbalance].

PMID- 17184099
TI  - Impact of the fetal pulse oximetry on the obstetrical decision in the theoretical
      setting.
AB  - OBJECTIVE: to assess whether fetal oxymetry reduces the intervention rate in a
      "theoretical setting". STUDY DESIGN: Data bank including 93 cases where a fetal
      oxymetry had been used for suspicion of fetal distress. Subjects-Two sets of
      labor charts were constructed for each case. One included relevant data with the
      saturometry, the other included relevant data without the saturometry.
      INTERVENTION: Theoretical setting: 3 obstetricians, unaware of study aim of the
      obstetrical outcomes. Each case was presented first without the saturometry; in a
      second reading, its result was available. OUTCOMES: Number of extractions.
      Consensus between experts. STATISTICS: descriptive and paired non parametric
      tests. RESULTS: The global intervention rate was lower (47% versus 52%; p<0.05)
      and the consensus higher, using monitoring and saturometry than using monitoring
      only. CONCLUSION: In a theoretical setting, the use of saturometry in suspicious
      cardiotocography (CTG) may help reduce the risk of invasive procedures.

PMID- 17184098
TI  - [Maintenance care. The peripherally-inserted central catheter. (3 of 4)].

PMID- 17184101
TI  - Outcome of conventional IVF and ICSI on sibling oocytes in patients suffering
      from teratospermia.
AB  - OBJECTIVE: To compare the outcomes of conventional IVF and ICSI on sibling
      oocytes. DESIGN: Retrospective analysis. METHODS: Performance of ICSI on part of
      the oocytes and IVF on the remaining portion during the same cycle (sibling
      oocytes). PATIENTS: 135 couples (141 cycles) with male subfertility or with
      idiopathic infertility. RESULTS: Globally, the fertilization rate was not
      different between the ICSI and IVF, however, in patients with severe
      teratospermia, it was higher after ICSI (56.2 vs. 44.2 %, p<0.05). The
      fertilization failure rate was higher in the IVF group than in the ICSI group,
      globally, (12.1 % vs 2.8 %, p = 0.005), as well in patients with severe
      teratospermia. In the latter group, a higher number of top quality embryos were
      obtained after ICSI than after IVF. Of 57 cycles with severe teratospermia, only
      ICSI-embryos were transferred in 24, while only IVF-embryos were transferred in
      11, resulting respectively in 8 and 3 clinical pregnancies. CONCLUSION: This
      study underscores that ICSI is useful in patients with teratospermia.
      Nevertheless, considering the chances of obtaining a successful fertilization
      after IVF and lower risk of chromosomal aberrations, we recommend performing both
      IVF and ICSI on sibling oocytes during the first treatment cycle in patients with
      teratospermia.

PMID- 17184100
TI  - Endometriosis in a woman with mosaic Turner's syndrome: case report.
AB  - The coexistence of endometriosis and Turner's syndrome is extremely rare, and
      therefore poses certain questions on the mechanisms of endometriosis. We present
      a case of a 27-year-old woman with Turner's syndrome [(46, X(x) (q10); 45X],
      primary amenorrhea and menopausal hormonal profile in which peritoneal
      endometriosis was revealed laparoscopically.

PMID- 17184102
TI  - Low and ultra low-dose estrogen therapy for climacteric symptom control-
      preliminary report.
AB  - INTRODUCTION: Recent clinical trials have caused physicians to reconsider the use
      of hormone therapy (HT). Low-dose therapy has been proposed for those patients
      who tolerate standard doses poorly. OBJECTIVE: to evaluate low-dose and ultra low
      dose estrogen therapy (ET) for vasomotor symptom control. MATERIALS AND METHOD:
      Thirty five healthy postmenopausal women with moderate to severe climacteric
      symptoms were recruited. Symptoms were evaluated at baseline and three months
      after the beginning of treatment by a modified Kupperman's index (KI).
      Endometrial thickness was assessed with pelvic ultrasonography. Patients were
      randomly assigned to one of these therapies: I) Esterified conjugated estrogens
      (ECE) 0.156 mg/day (ultra low-dose) (n = 18) or II) ECE 0.312 mg/day (low-dose)
      (n = 17) for 12 weeks. Statistical analysis was done with student's t test for
      independent and paired samples. RESULTS: In groups I and II, the abandon rate was
      33.3% and 47.0%, respectively. No differences were found among the groups in
      general data nor in KI. The KI at the end of the study was 47.8+/-37.9 and 48.9+/
      33.2 for group I and group II, respectively, for a mean decrease of 32.1% and 37%
      without differences between the groups. When comparing each group separately, KI
      decreased in group 1, but without statistical significance. In group II there was
      significant decrease in KI. Endometrial thickness increased from 2.5+/-1.0 to
      4.2+/-1.7 mm in group I, and from 3.5+/-1.3 to 6.0 +/-1.4 mm in group II.
      CONCLUSION: low dose and ultra-low dose ET were useful in decreasing climacteric
      symptoms.

PMID- 17184104
TI  - Recognition of women at risk for fracture and intervention with fast-acting
      therapies.
AB  - Fractures can be a devastating outcome of osteoporosis, a disease that
      disproportionately affects postmenopausal women. Once a patient sustains a
      fragility fracture, the risk of future fractures quickly increases, providing
      compelling rationale for identifying patients at risk and initiating treatment
      that works rapidly. Comprehensive risk assessment beyond bone mineral density
      measurement is needed to identify women for further clinical assessment and
      intervention. Effective management of osteoporosis can improve the long-term
      health of postmenopausal women with osteoporosis. A number of oral therapies have
      demonstrated a rapid onset of fracture risk reduction. Risedronate has shown
      significant reductions in vertebral and nonvertebral fracture risk after 6 months
      and alendronate after 1 year of therapy. Teriparatide also has demonstrated both
      vertebral and nonvertebral fracture efficacy and should be considered an
      effective therapeutic

PMID- 17184103
TI  - Testicular sperm aspiration (TESA) in 327 ICSI cycles.
AB  - OBJECTIVE: To evaluate the efficiency of testicular sperm recovery by testicular
      sperm aspiration (TESA) in an IVF program. DESIGN: Retrospective Data Analysis.
      SETTING: The Center of Reproductive Medicine, Department of Obstetrics and
      Gynecology, Arcispedale S. Maria Nuova, Reggio Emilia, Italy. PATIENT(S): Couples
      undergoing TESA/ICSI for obstructive or nonobstructive azoospermia.
      INTERVENTION(S): ESA/ICSI. MAIN OUTCOME MEASURE(S): Efficiency of testicular
      sperm recovery, fertilization rate, implantation rate and clinical pregnancy
      rate. RESULT(S): Between March 1, 1997 and March 31, 2005, 327 cycles of
      TESA/ICSI were performed in couples in which the male had obstructive or
      nonobstructive azoospermia. The efficiency of testicular sperm recovery was 99.4%
      and 99.3%, fertilization rate 57.1% and 49.1%, implantation rate 5.7% and 6.2%,
      and the clinical pregnancy rate 12.9% and 15.4% in men with obstructive and
      nonobstructive infertility, respectively. CONCLUSION(S): The efficiency of TESA
      is very high in both obstructive and nonobstructive azoospermia. Because TESA is
      less invasive than TESE, it should be considered a valuable alternative to TESE
      in IVF programs, especially in setting where resources are limited.

PMID- 17184105
TI  - [Hypertrophy of the heart: calcineurin-NFAT pathway may be a new therapeutic
      target].

PMID- 17184106
TI  - [Recent advance in predicting oral bioavailability].

PMID- 17184107
TI  - [Microdialysis in mice and its application in drug delivery system].

PMID- 17184108
TI  - Colon-specific delivery tablets of sodium 4-aminosalicylic acid.
AB  - AIM: To prepare a new oral colon-specific delivery formulation and to investigate
      the release profile in vitro and the colon-specific delivery property in vivo in
      dogs. METHODS: Sodium 4-aminosalicylic acid was selected as the model drug. The
      combination of Eudragit RL30D and RS30D were used as sustained-release film, and
      Eudragit FS30D used as enteric film, which was expected to release drug depending
      on pH and time. The release profile of tablets was studied in three phosphate
      buffers with the pH 6.5, 7.0 or 7.4 for 12 h after a simulated gastric presoak
      for 2 h in 0.1 mol x L(-1) HCl. The tablets were radiolabelled with 99mTc to make
      their release times and positions in the gastrointestinal tract be followed using
      a gamma camera. RESULTS: For the in vitro study, there was no drug released in
      0.1 mol x L(-1) HCl for 2 h, and release occurred slowly when pH was above 6.5.
      Drug was released faster while pH was higher. For the in vivo study, the coated
      tablets remained intact in the upper gastrointestinal tract, and drug release
      began after the colonic arrival. The uncoated tablets, however, disintegrated in
      the stomach of the dogs rapidly. CONCLUSION: The coating could protect the drug
      until the tablets reached the ascending colon, where drug was released slowly for
      over 10 h.

PMID- 17184109
TI  - [Preparation of magnetic solid liposome nanoparticles of paclitaxel].
AB  - AIM: To study a new way to prepare high-dosage paclitaxel entrapped magnetic
      targeted nanoparticles and evaluate its quality. METHODS: Fe3O4 nanoparticles are
      prepared by co-depositing, at the same time ultrasonic is used to decrease soft
      agglomerate of nanoparticles and increase disperse level of it. The property of
      nanoparticles surface is improved to make the integrating of liposome and
      nanoparticle to be tighter. At last, paclitaxel entrapped magnetic solid liposome
      nanoparticles have been prepared by microemulsion-curing under low-temperature.
      The loading efficiency and encapsulating rate were determined by reverse-phase
      high-perfomance chromatography. RESULTS: The nanoparticles have spherical shape.
      Diameter of nanoparticle ranged from 150 nm to 170 nm. 98.29% of the drug is
      entrapped in the particle. CONCLUSION: Magnetic susceptibility of nanoparticles
      is high, and the nanoparticles meet with the demand of targeted delivery system.

PMID- 17184110
TI  - [Effects of absorption enhancers on intestinal absorption of lumbrokinase].
AB  - AIM: To explore the intestinal absorption characteristics of lumbrokinase (YJM-I)
      in the absence or presence of various absorption enhancers and to find the
      optimum intestinal site for YJM-I absorption. METHODS: The absorption kinetics
      and absorption intestinal sites for YJM-I absorption were investigated with the
      method of diffusion cell in vitro, duodenum bolus injection, recirculating
      perfusion and in situ duodenum perfusion in vivo. RESULTS: YJM-I could be
      transported into blood and kept its biological activity across intestinal
      endothelial membrane after administration via duodenum site, whereas with lower
      bioavailability. Some of the absorption enhancers were shown good enhancement
      effects on intestinal absorption of YJM-I in vitro and in situ experiments. The
      order of enhanced efficiencies of various enhancers on duodenum, ileum and
      jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1%
      SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD.
      The order of enhanced efficiencies of various enhancers on duodenum absorption of
      YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5%
      SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD. CONCLUSION: The
      results indicated that the absorption of YJM-I could be enhanced by various
      enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore,
      bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I
      absorption.

PMID- 17184111
TI  - [Preparation and evaluation of clarithromycin emulsion for injection].
AB  - AIM: To prepare clarithromycin emulsion and investigate its pharmacokinetics in
      rats. And to do irritation test of the emulsion. METHODS: High pressure
      homogenization method was used to prepare clarithromycin emulsion, and the
      Nicomp380 machine was used to test the mean particle size and zeta-potential of
      clarithromycin emulsion. Irritation of emulsion was also evaluated compared with
      the positive control of clarithromycin solution using rat paw lick test and
      rabbit ear vein irritation test. Microbiological assay method was used for
      determining the drug concentration in plasma. Pharmacokinetics of two dosage
      forms in rats was also studied. RESULTS: The mean particle size and zeta
      potential of clarithromycin emulsion were 156 nm and -31.8 mV, respectively. The
      emulsion was stable during the storage time at 4 degrees C for 6 month. The pain
      caused by emulsion reduced significantly compared with that of clarithromycin
      solution based on the results of rat paw lick test and rabbit ear vein test. The
      drug concentration-time curves of clarithromycin emulsion and clarithromycin
      solution were similar and could be described by two compartment model. AUC(0-1)
      of clarithromycin emulsion and clarithromycin solution were (66.76 +/- 16.34) and
      (59.00 +/- 11.20) microg x h x mL(-1), respectively. CONCLUSION: Stable emulsion
      could be prepared using high pressure homogenization method, and irritation
      caused by i.v. injection could be reduced significantly by using clarithromycin
      emulsion.

PMID- 17184112
TI  - [Combined effect of cosolvent and cyclodextrin on solubilization of insoluble
      drugs].
AB  - AIM: To investigate the combined effect of cosolvent and cyclodextrin (CD) on
      solubilization of insoluble drugs. METHODS: Phase-solubility method was applied
      to determine solubilization of two diterpenoids in cosolvent / cyclodextrin
      combinations. The combined effect was evaluated and explained with an established
      mathematical model, and the model parameters were calculated by means of
      nonlinear regression analysis. RESULTS: The strong agreement between the
      predicted and the observed solubility data supports the validity of the proposed
      model, with the determination coefficients of two regression models were 0.993
      and 0.992, separately. CONCLUSION: The validated mathematical model can be used
      to explain and predict the combined solubilization of the two insoluble drugs in
      different cosolvent systems.

PMID- 17184113
TI  - [Evaluation of antioxidant activity of Radix Linderae and other two Chinese drugs
      using TLC-bioautography].
AB  - AIM: To evaluate the antioxidant capacity and quality of traditional Chinese
      medicines using TLC-bioautography. METHODS: Two chromatograms of each crude drug
      sample were obtained, after developing, by spraying with 1,1-diphenyl-2
      picrylhydrazyl (DPPH) solution in ethanol and classical stained reagents,
      separately. The images sprayed with DPPH solution were captured under light after
      the plates were heated at 40 degrees C for 30 min, and scanned using video scan
      software to get peak areas of active compounds. RESULTS: Total peak areas of the
      spots on TLC were calculated to evaluate the antioxidant capacity of the tested
      crude drugs from different habitats and sources. The results indicated that Radix
      Linderae cultivated in Tiantai (Zhejiang province), Cortex Magnoliae Officinalis
      cultivated in Liangshan (Sichuan province), and Fructus Perillae acquired in
      Shanghai have the highest scavenging properties towards DPPH in their respective
      TLC-autographic assays. Norisoboldine, magnolol and honokiol, luteolin, apigenin
      and an unknown compound "U" proved to be the major antioxidant components in the
      corresponding crude drugs as they contribute the dominating peak areas to the
      total ones. CONCLUSION: TLC-bioautography can not only be used for screening of
      the components with antioxidant potency but also for the purpose of quality
      evaluation of traditional Chinese medicines at the same time, and the method
      proved to be selective, simple and reproducible.

PMID- 17184114
TI  - [The production of gastrodin through biotransformation of p-hydroxybenzaldehyde
      by cell suspension culture of Datura stramonium].
AB  - AIM: To investigate the production of p-hydroxymethylphenol-beta-D-glucoside
      (gastrodin) through biotransformation by plant cell suspension cultures. METHODS:
      Using cell suspension cultures of Datura stramonium to convert the exogenous p
      hydroxybenzaldehyde into gastrodin was conducted and the converted compounds were
      separated with a combination of multi-chromatography. Their chemical structures
      were determined on the basis of spectral analysis and chemical evidence. RESULTS:
      The conversion procedure of p-hydroxybenzaldehyde into gastrodin by Datura
      stramonium cell suspension cultures was established. The synthesized gastrodin
      (II) was isolated from the fermental liquor and identified by spectral analysis.
      At the same time, the p-hydroxybenzyl alcohol (I) converted through
      biotransformation of p-hydroxybenzaldehyde by cell suspension cultures of Datura
      stramonium was also isolated and identified. Two compounds were also isolated
      from the cell cultures and they were identified as beta-D-furanoallulose (III)
      and n-butyloxystyryl-beta-D-pyranoallulose (IV). CONCLUSION: Datura stramonium
      grown in suspension cultures can convert exogenous p-hydroxybenzaldehyde into the
      corresponding gastrodin.

PMID- 17184115
TI  - [The inhibition of CYP2C9 isoenzyme in Cunninghamella blakesleeana AS 3. 910].
AB  - AIM: To investigate the variation of CYP2C9 isoenzyme activity in the microbial
      model in response to inhibitors of CYP2C9. METHODS: Using C. blakesleeana AS 3.
      910 as a model strain, the impact of CYP2C9 inhibitors on the metabolites yields
      of CYP2C9 substrates was determined and the drug-drug interactions among CYP2C9
      substrates were evaluated. Liquid chromatography-mass spectrometry was used to
      analyze biotransformation products. RESULTS: Benzbromarone decreased the yield of
      4'-hydroxytolbutamide from 100% to 14.5%; sulfaphenazole decreased the yield of O
      demethylindomethacin from 75.2% to 9.9%; valproic acid decreased the yield of 4'
      hydroxydiclofenac from 98.6% to 2.7%, separately. Tolbutamide, indomethacin and
      diclofenac interacted with each other, resulting in the decreased formation of
      metabolites catalyzed by CYP2C9. CONCLUSION: Three CYP2C9 inhibitors inhibit the
      activity of CYP2C9 isoenzyme in C. blakesleeana AS 3. 910 differently, and there
      are drug-drug interactions among CYP2C9 substrates.

PMID- 17184116
TI  - [Hypersensitization of alpha-adrenoreceptor of artery smooth muscle in
      hypertensive rats and hypertensive patients].
AB  - AIM: To investigate the hypersensitization of alpha-adrenoreceptor of artery
      smooth muscle in hypertensive patients and rats and the mechanisms concerned.
      METHODS: Isometric tension of artery ring segments was recorded by a sensitive
      myograph system in vitro and the relative amount of alpha-adrenoreceptor mRNA was
      quantified by a real-time PCR. RESULTS: Noradrenaline (NA)-induced concentration
      contraction curve of mesenteric artery segments in spontaneously hypertensive
      rats (SHR) was more potent than that in Wistar-Kyoto (WKY) rats. The E(max) of NA
      in SHR was 1.82 times of that of WKY. The concentration-contractile curve induced
      by NA in great omental arteries of hypertensives significantly shifted toward
      left and the pD2 value of NA was larger than that of normotensives. After organ
      culture, the concentration-contractile curves of SD rat mesenteric artery induced
      by NA shifted toward left with significantly increased E(max). The relative
      amounts of mRNA for alpha1-adrenoreceptor was increased, but mRNA level for
      alpha2-adrenoreceptor did not change. CONCLUSION: The sensitivity of alpha1
      adrenoreceptor of artery smooth muscle in hypertensive man and rat is enhanced,
      suggesting alpha1-adrenoreceptor is upregulated.

PMID- 17184117
TI  - Apoptosis induced by DNA primase inhibitor 3,3'-diethyl-9-methylthia-carbocyanine
      iodide in human leukemia HL-60 cells.
AB  - AIM: To investigate apoptosis induced by 3,3'-diethyl-9-methylthia-carbocyanine
      iodide (DMTCCI), an inhibitor of DNA primase found in our previous study, and the
      mechanism of DMTCCI in human myelogenous leukemia HL-60 cells. METHODS: HL-60
      cells were cultured in RPMI-1640 medium and treated with different concentrations
      of DMTCCI. MTT assay was used to detect growth inhibition. Flow cytometry and DNA
      ladders were used to detect apoptosis. Western blotting was used to observe the
      expression of survivin, Bcl-xL, Bad, Bax, Bcl-2, caspase-9, caspase-3, caspase-6,
      PARP, DFF45 and lamin B protein. Caspase-3 activity was measured by ApoAlert
      Caspase-3 Assay Kit. RESULTS: DMTCCI inhibited proliferation of human leukemia HL
      60 cells with IC50 value of 0.24 micromol x L(-1). The results of flow cytometry
      and DNA ladders showed that DMTCCI could induce apoptosis of HL-60 cells. The
      expression levels of protein survivin and Bcl-xL were down-regulated, Bad and Bax
      were up-regulated, while Bcl-2 protein had no change in response to DMTCCI
      treatment in HL-60 cells. Treatment of HL-60 cells with DMTCCI induced the
      proteolytic cleavage of caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B
      protein. Caspase-3 activity apparently increased at 3 h and reached a peak at 12
      h after exposure to 1 micromol x L(-1) of DMTCCI in HL-60 cells. CONCLUSION:
      DMTCCI inhibited proliferation and induced apoptosis of human leukemia HL-60
      cells. Bcl-2 family proteins, survivin and caspases family proteins might play a
      role in the apoptosis process induced by DMTCCI.

PMID- 17184118
TI  - [Modification of novel oxazolidinone derivatives at C-5 side chain and their
      antibacterial activities].
AB  - AIM: To modify the C-5 side chains of the oxazolidinone derivatives and evaluate
      their in vitro antibacterial activities preliminarily. METHODS: The title
      compounds were synthesized in 9 - 12 steps with the starting material 3
      fluoroaniline and their in vitro antibacterial activities were examined by using
      Mueller-Hinton broth dilution method. RESULTS: Thirty new compounds were designed
      and synthesized, in which eighteen novel title compounds were prepared and their
      structures were confirmed by 1H NMR and ESI-MS. Eleven compounds showed
      antibacterial activities to a certain extent, among them compounds 7a, 9a and 11a
      displayed promising activity. CONCLUSION: Compounds 7a, 9a and 11a were worth
      further studying.

PMID- 17184119
TI  - [Synthesis and antibacterial activities of 7-{4-[2-[2-substituted-4-((5S)-5
      acetylaminomethyl-2-oxo-oxazolidin-3-yl)}-phenyl] -ethyl]-piperazin-1-yl}
      fluoroquinolones].
AB  - AIM: To find out new oxazolidinone-fluoroquinolone derivatives with high
      antibacterial activity. METHODS: Some 7-{4-[2-[2-substituted-4-((5S)-5-
      acetylaminomethyl-2-oxo-oxazolidin-3-yl)-phenyl]-ethyl]-piperazin-1-yl}
      fluoroquinolones were designed and synthesized, and their antibacterial
      activities were tested in vitro. RESULTS: Twenty target compounds were obtained
      and their structures were confirmed by 1H NMR and MS. The target compounds had
      high antibacterial activities in vitro, especially, the activity of compound 22
      against Enterococcus faecium was 16-fold and 64-fold more potent than that of
      linezolid and norfloxacin, respectively, and its MIC value against Staphylococcus
      aureus was 4-fold lower than that of linezolid. CONCLUSION: The oxazolidinone
      fluoroquinolone derivatives improved the antibacterial activities.

PMID- 17184120
TI  - [Active constituents from Aloe arborescens as BACE inhibitors].
AB  - AIM: To seek for new components as BACE inhibitors from Aloe arborescens.
      METHODS: The chemical constituents were isolated by chromatographic methods and
      their structures were elucidated on the basis of spectral analysis. RESULTS:
      Eight compounds were isolated and their structures identified as 6'-O-isobutyryl
      aloenin A (1), aloenin A (2), aloe-emodin (3), (E)-2-acetonyl-8-(2'-O-feruloxyl)
      beta-D-glucopyranosyl-7-methoxy-5-methyl-chromone (4), 7-O-methylaloeresin A (5),
      babarloin A (6), elgonica-dimer A (7), and elgonica-dimer B (8), separately.
      CONCLUSION: Compound 1 is a new compound, and compound 4 was isolated from A.
      arborescens for the first time. Pharmacological tests indicated that 2, 4, 5 and
      6 have moderate inhibitory active on BACE.

PMID- 17184121
TI  - [Identification of hydroxylate metabolites of daidzein and its sulfate conjugates
      in rat urine by LC-ESI/MS(n)].
AB  - AIM: To identify the hydroxylate metabolites and its sulfate conjugates of
      daidzein in rat urine. METHODS: Urine samples from 0 - 24 h were collected after
      single ig dose of 500 mg x kg(-1) daidzein to each of six rats. The urine samples
      were purified by SPE column (SPE C18) and analyzed with liquid chromatographic
      tandem electrospray ionization ion trap mass spectrometry (LC-ESI/MS(n)) for
      potential metabolites. RESULTS: Several new hydroxylate metabolites and its
      sulfate conjugates were found and identified in rat urine. CONCLUSION: LC
      ESI/MS(n) is proved to be a simple, rapid, sensitive and specific technique for
      identification of the hydroxylate metabolites and its sulfate conjugates of
      daidzein in rat urine.

PMID- 17184122
TI  - [Quality analysis and evaluation of Rhizoma Coptidis under different cultivation
      conditions].
AB  - AIM: To develop methods for the fingerprint analysis of Rhizoma Coptidis and the
      determination of berberine, palmatine and jatrorrhizine in Rhizoma Coptidis, and
      analyze the contents of these three alkaloids in Rhizoma Coptidis under different
      cultivation conditions, from different areas and processed with different
      methods. METHODS: Two methods (HPLC-UV and HPLC-MS) have been developed and used
      in fingerprint analysis of Rhizoma Coptidis. An HPLC method was used to determine
      the contents of three alkaloids. RESULTS: With HPLC-MS techniques, seven major
      chromatographic peaks in the fingerprint analysis of Rhizoma Coptidis were
      identified by their MS spectra and compared with the reference standards. In
      different cultivation conditions, shading conditions and growing ages have
      obvious influence on the contents of three alkaloids in Rhizoma Coptidis, while
      planting density was not the major factor that influenced the contents of three
      alkaloids. The contents of three alkaloids of Coptidis samples were almost higher
      than those of Coptidis reference material. For Coptidis samples from different
      cultivation area, the contents of these three alkaloids were different greatly.
      For Coptidis samples processed with different methods, the contents of three
      alkaloids were not influenced obviously by processing methods. CONCLUSION: The
      results showed that the ecology cultivation method to replace the traditional
      shading method was feasible and provided the theoretical foundation for
      scientifically processing Rhizoma Coptidis.

PMID- 17184123
TI  - [Identification of the degradation compounds of cefathiamidine by liquid
      chromatography-tandam mass spectrometry].
AB  - AIM: To identify the degradation compounds of cefathiamidine by a liquid
      chromatography-tandam mass spectrometry (LC-MS). METHODS: According to the
      accelerated storage condition, two main degradation compounds of cefathiamindine
      were its hydrolytic products. Cefathiamidine was separated on a C18 column, with
      1% acetate solution-acetonitrile (85 : 15) as mobile phase. The mass spectra and
      MS/MS spectra were obtained with set at the positive ion mode. Combined the UV
      spectra and the chromatography behavior, the structures of two degradation
      compounds were identified. RESULTS: The method can be used for the separation of
      the degradation compounds of cefathiamindine. The two major degradation compounds
      were desacetylcefathiamidine and cefathiamidine lactone. CONCLUSION: The method
      is rapid, sensitive and specific, and it is suitable for the identification of
      the degradation compounds of cephalosporin.

PMID- 17184124
TI  - [A novel microemulsion electrokinetic chromatography for measuring lipid-water
      partition coefficients of pharmaceuticals].
AB  - AIMS: To establish a novel microemulsion electrokinetic chromatography (MEEKC)
      method for measuring lipid-water partition coefficients ( logP(ow)) of
      pharmaceuticals without using microemulsion phase marker in order to avoid the
      error from tracing the migration time of microemulsion phase. METHODS: The
      migration time of microemulsion phase (t(me)) was obtained by non-linearity
      fitting with logP(ow) values from literature and measured migration time (t(m))
      of a series of organic compounds, a calibration curve for estimating logP(ow) of
      pharmaceuticals was thus obtained. In addition, the accuracy of the values
      measured by MEEKC was evaluated. RESULTS: The logP(ow) values of 4
      pharmaceuticals measured by MEEKC method presented in this paper were close to
      those determined by shake-flask method, and the average error between values from
      two methods was 0.15 logarithm units. Furthermore, according to the suggested
      theory, the measurement accuracy of logP(ow) is correlated with different t(m) in
      MEEKC. CONCLUSION: The proposed method is simple, rapid, reproducible, and
      reliable with high measurement accuracy, which can be useful to estimate lipid
      water partition coefficients of pharmaceuticals.

PMID- 17184129
TI  - Trapping transient protein-protein interactions in polyketide biosynthesis.
AB  - Transient biomolecular interactions are essential for biological processes, but
      strategies for studying them have remained elusive. A paper in this issue shows
      how natural enzymatic activities can be exploited to examine protein-protein
      interactions in fatty acid synthase.

PMID- 17184130
TI  - Evolving sensitivity.
AB  - Engineering gene circuits with novel functions holds promise for broad
      applications in biology, engineering, and medicine. Directed evolution
      complements rational design as an important strategy for optimizing gene circuits
      and circuit elements.

PMID- 17184131
TI  - Small molecules keep mitotic kinases in check.
AB  - The remarkable progress in the discovery of small molecules that target protein
      kinases continues, and two recent reports have described alternative approaches
      to this task: homology modeling and phenotype-based screening. Compounds
      targeting the nucleotide binding pockets of polo-like kinases in particular
      provide significant new insights into the molecular mechanisms controlling cell
      division phenotypes.

PMID- 17184132
TI  - Mechanism-based protein cross-linking probes to investigate carrier protein
      mediated biosynthesis.
AB  - Fatty acid, polyketide, and nonribosomal peptide biosynthetic enzymes perform
      structural modifications upon small molecules that remain tethered to a carrier
      protein. This manuscript details the design and analysis of cross-linking
      substrates that are selective for acyl carrier proteins and their cognate
      condensing enzymes. These inactivators are engineered through a covalent linkage
      to fatty acid acyl carrier protein via post-translational modification to contain
      a reactive probe that traps the active site cysteine residue of ketosynthase
      domains. These proteomic tools are applied to Escherichia coli fatty acid
      synthase enzymes, where KASI and KASII selectively cross-link ACP-bound epoxide
      and chloroacrylate moieties. These mechanism-based, protein-protein fusion
      reagents also demonstrated cross-linking of KASI to type II polyketide ACPs,
      while nonribosomal peptide carrier proteins showed no reactivity. Similar
      investigations into protein-protein interactions, proximity effects, and
      substrate specificities will be required to complete the mechanistic
      understanding of these pathways.

PMID- 17184133
TI  - Construction and engineering of positive feedback loops.
AB  - Artificial positive feedback loops (PFLs) have been used as genetic amplifiers
      for enhancing the responses of weak promoters and in the creation of eukaryotic
      gene switches. Here we describe the construction and directed evolution of two
      PFLs based on the LuxR transcriptional activator and its cognate promoter, P luxI
      . The wild-type PFLs are completely activated by 10 nM of 3-oxo-hexanoyl
      homoserine lactone (OHHL). Directed evolution of LuxR increased the sensitivity
      of the feedback loops, resulting in systems that are completely activated at OHHL
      concentrations of 5 nM, or approximately 3 molecules per cell. The responses of
      the PFLs can also be modulated by adjusting inducer concentrations. These highly
      sensitive yet regulatable PFLs can be used to construct larger artificial genetic
      networks to gain understanding of the design principles of complex biological
      systems and are expected to find various applications in industrial fermentation
      and gene therapy.

PMID- 17184134
TI  - Phosphopeptide modification and enrichment by oxidation-reduction condensation.
AB  - Many cellular processes are regulated by the reversible phosphorylation of
      proteins. Despite the importance of monitoring protein phosphorylation, available
      methods to modify and enrich phosphopeptides from complex mixtures for subsequent
      mass spectrometric analysis are challenging. Here the oxidation-reduction
      condensation was shown for the first time to directly modify the phosphate of
      phosphopeptides and phosphoproteins. By coupling with a solid-phase resin, the
      oxidation-reduction condensation was validated for capture and recovery of
      phosphoserine-, phosphothreonine-, and phosphotyrosine-containing peptides from a
      peptide mixture. In addition, full-length phosphoproteins or phosphopeptides from
      a protein digestion were captured and recovered using the oxidation-reduction
      condensation, demonstrating its compatibility with protein mixtures. The strategy
      modifies all phosphopeptides, maintains high chemical selectivity, requires only
      two steps, and relies on commercially available reagents, suggesting that the
      oxidation-reduction condensation has the potential to enhance phosphopeptide
      enrichment methods and encourage development of efficient biochemical and
      proteomics tools targeting phosphorylation.

PMID- 17184136
TI  - Mechanism-based probe for the analysis of cathepsin cysteine proteases in living
      cells.
AB  - Mechanism-based probes are providing new tools to evaluate the enzymatic
      activities of protein families in complex mixtures and to assign protein
      function. The application of these chemical probes for the visualization of
      protein labeling in cells and proteomic analysis is still challenging. As a
      consequence, imaging and proteomic analysis often require different sets of
      chemical probes. Here we describe a mechanism-based probe, azido-E-64, that can
      be used for both imaging and proteomics. Azido-E-64 covalently modifies active
      Cathepsin (Cat) B in living cells, an abundant cysteine protease involved in
      microbial infections, apoptosis, and cancer. Furthermore, azido-E-64 contains an
      azide chemical handle that can be selectively derivatized with phosphine reagents
      via the Staudinger ligation, which enables the imaging and proteomic analysis of
      Cat B. We have utilized azido-E-64 to visualize active Cat B during infection of
      primary macrophages with Salmonella typhimurium , an facultative intracellular
      bacterial pathogen. These studies demonstrated that active Cat B is specifically
      excluded from Salmonella -containing vacuoles, which suggests that inhibition of
      protease activity within bacteria-containing vacuoles may contribute to bacterial
      virulence.

PMID- 17184135
TI  - HIV-1 reverse transcriptase structure with RNase H inhibitor dihydroxy benzoyl
      naphthyl hydrazone bound at a novel site.
AB  - The rapid emergence of drug-resistant variants of human immunodeficiency virus,
      type 1 (HIV-1), has limited the efficacy of anti-acquired immune deficiency
      syndrome (AIDS) treatments, and new lead compounds that target novel binding
      sites are needed. We have determined the 3.15 A resolution crystal structure of
      HIV-1 reverse transcriptase (RT) complexed with dihydroxy benzoyl naphthyl
      hydrazone (DHBNH), an HIV-1 RT RNase H (RNH) inhibitor (RNHI). DHBNH is effective
      against a variety of drug-resistant HIV-1 RT mutants. While DHBNH has little
      effect on most aspects of RT-catalyzed DNA synthesis, at relatively high
      concentrations it does inhibit the initiation of RNA-primed DNA synthesis.
      Although primarily an RNHI, DHBNH binds >50 A away from the RNH active site, at a
      novel site near both the polymerase active site and the non-nucleoside RT
      inhibitor (NNRTI) binding pocket. When DHBNH binds, both Tyr181 and Tyr188 remain
      in the conformations seen in unliganded HIV-1 RT. DHBNH interacts with conserved
      residues (Asp186, Trp229) and has substantial interactions with the backbones of
      several less well-conserved residues. On the basis of this structure, we designed
      substituted DHBNH derivatives that interact with the NNRTI-binding pocket. These
      compounds inhibit both the polymerase and RNH activities of RT.

PMID- 17184137
TI  - The changing dynamics of systolic hypertension and accompanying treatments.

PMID- 17184138
TI  - Psychosis-related disturbances. Psychosis, agitation, and disinhibition in
      Alzheimer's disease: definitions and treatment options.
AB  - Approximately 50% to 80% of persons diagnosed with Alzheimer's disease (AD) have
      some type of behavioral or psychiatric condition (eg, agitation, psychosis,
      and/or disinhibition). Agitation is defined in the context of restlessness,
      irritability, and resistiveness. Psychosis is recognized as a disturbance in the
      perception of objective reality. Disinhibition means a chronic loss of social
      restraint. In the case of AD, disinhibition can present as aggression,
      hyperactivity, and socially intrusive behavior. Such conditions can be burdensome
      for physicians and caregivers to manage. Consequences may include caregiver
      burnout or illness, patient abuse, and even institutionalization for the patient.
      Management of behavioral disturbances is no longer primarily handled by
      psychiatrists, but is now entering the realm of family practice and primary care.
      This article provides evaluation methods and treatment options for the
      aforementioned behavioral disturbances.

PMID- 17184139
TI  - Systolic hypertension.
AB  - Approximately one-third of the adult population has hypertension. Large-scale
      clinical trials have convincingly demonstrated that the treatment of isolated
      systolic and systolic/diastolic hypertension reduces rates of total mortality,
      cardiovascular mortality, and stroke in older adults, yet control of systolic
      hypertension remains poor. This article reviews systolic blood pressure as a
      cardiovascular risk factor and discusses effective management of elevated
      systolic blood pressure. The role of combination therapy is emphasized, focusing
      on the combination of a calcium-channel blocker and an angiotensin-converting
      enzyme inhibitor. In addition to blood pressure-lowering efficacy, the
      combination of these two classes of metabolically neutral agents may offer
      benefit in terms of tolerability and cognitive function.

PMID- 17184140
TI  - Yellowish-white papules on forehead.

PMID- 17184141
TI  - Effects of 5-hydroxytryptamine on the short-circuit current across the small
      intestine of the gerbil (Gerbillus cheesmani) in different dietary states.
AB  - The effects of serosally added 5-hydroxytryptamine (5-HT, 100 microM) on the
      short circuit-current (Isc) across jejunum and ileum taken from fed, starved and
      undernourished (Gerbillus cheesmani) were investigated. The effects of the
      neurotoxin, tetrodotoxin (TTX, 10 microM) on the basal Isc as well as on the
      maximum increase in Isc induced by 5-HT were also studied. There were regional
      variations in the basal Isc as well as in the way by which the small intestine
      responds to 5-HT. The basal Isc was greater in jejunum than in ileum and such
      differences were TTX-sensitive. The maximum increase in Isc, which results from
      addition of 5-HT, was higher in jejunum than in ileum under all three feeding
      conditions. TTX reduced the maximum increase in Isc induced by 5-HT across
      stripped and intact intestine of the two regions in the three nutritional states.
      The 5-HT-induced Isc in the jejunum of both starved and undernourished gerbils
      and in the ileum of starved animals was the function of both submucosal and
      myenteric plexus. In jejunum and ileum taken from starved and undernourished
      gerbils the 5-HT-induced Isc was both chloride- and bicarbonate-dependent. Thus
      the results indicated that both starvation and undernourishment increase that
      response and such increases were TTX-sensitive and both chloride- and bicarbonate
      dependent.

PMID- 17184142
TI  - Dynamics of tissue ubiquitin pools and ubiquitin-proteasome pathway component
      activities during the systemic response to traumatic shock.
AB  - Based on the biological significance of the ubiquitin-proteasome pathway (UPP)
      and its potential role during sepsis, burns and ischemia-reperfusion injury, we
      hypothesized that the systemic response to traumatic shock (TS) is accompanied by
      tissue-specific UPP alterations. Therefore, we studied tissue ubiquitin pools,
      chymotryptic- and tryptic-like proteasome peptidase activities and ubiquitin
      protein ligation (UbPL) rates in skeletal muscle, heart, lung, liver, spleen and
      kidney using a clinically relevant porcine model (bilateral femur
      fracture/hemorrhage followed by fluid resuscitation). TS induced a systemic
      reduction of tissue-specific high molecular mass ubiquitin-protein conjugates
      (>50 kDa). Free ubiquitin was unaffected. The dynamic organ patterns of ubiquitin
      pools paralleled the typical physiological response to TS and resuscitation.
      Reduction of ubiquitin-protein conjugates was most pronounced in heart and lung
      (p<0.05 vs. control) and accompanied by significant increases in proteasome
      peptidase and UbPL activities in these organs. Unlike all other tissues, spleen
      proteasome peptidase and UbPL activities were significantly reduced 10 h after
      TS. These findings support the concept that the UPP could play an important role
      in regulation of cell functions during the early whole-body response to TS. The
      UPP might be a therapeutic target to improve the metabolic care after TS,
      particularly in the heart, lung, and spleen.

PMID- 17184143
TI  - Increased insulin sensitivity in patients with anorexia nervosa: the role of
      adipocytokines.
AB  - Anorexia nervosa (AN) is characterized by self-induced starvation leading to
      severe weight and fat loss. In the present study, we measured fasting plasma
      levels of adiponectin, leptin, resistin, insulin and glucose in 10 women with a
      restrictive type of AN and in 12 healthy women (C). Insulin sensitivity was
      determined according to homeostasis model assessment of insulin resistance (HOMA
      R). Plasma resistin, leptin and insulin levels were significantly decreased,
      whereas plasma adiponectin levels were significantly increased in patients with
      AN compared to the C. HOMA-R was significantly decreased in patients with AN
      compared to the C group. Plasma adiponectin and leptin concentrations negatively
      and positively correlated with the body mass index and percentage body fat in
      both groups. Plasma adiponectin levels were negatively related to plasma insulin
      levels in the AN group only. In conclusion, we demonstrated that AN is associated
      with significantly decreased plasma leptin and resistin levels, markedly
      increased plasma adiponectin levels and increased insulin sensitivity. Plasma
      leptin and adiponectin levels were related to the body size and adiposity.
      Hyperadiponectinemia could play a role in increased insulin sensitivity of
      patients with AN. Neither body size and adiposity nor insulin sensitivity are the
      major determinants of plasma resistin levels in AN.

PMID- 17184144
TI  - Integrative hypothesis for Huntington's disease: a brief review of experimental
      evidence.
AB  - Huntington's disease (HD) is a demential, neurodegenerative inheritable disease
      affecting middle-aged patients. HD is characterized by uncontrolled choreiform
      movements, psychiatric symptoms and cognitive decline. Histopathological changes
      in HD brains reveal a considerable damage to basal ganglia, particularly
      affecting middle-sized spiny neurons from the caudate-putamen region.
      Neurochemical changes are specifically oriented to deplete GABAergic and
      cholinergic systems, while molecular alterations include an increased expression
      of CAG trinucleotide at exon 1 from the huntingtin (htt) gene, as well as
      aggregation of mutant htt. Although several hypotheses regarding the mechanisms
      by which neurotoxicity is triggered in HD brains have been suggested on the basis
      of experimental evidence, so far it remains not clear which of them are
      predominant or whether they are complementary. Recent experimental evidence
      through transgenic mice models reveal an interesting interaction between expanded
      CAG triplets, mutant htt, and the increase in toxic metabolites from the
      kynurenine pathway. Further evidence supports the assumption that different toxic
      mechanisms (i.e. excitotoxicity, energy metabolism impairment, inflammatory
      events, oxidative stress, etc.) are confluent and depend on each other. In this
      review we will briefly summarize some of those findings and propose a final
      integrative hypothesis for HD.

PMID- 17184145
TI  - Effect of certain immunosuppressants on non-specific immunity cells in murine
      corneal grafts: study on early phases after transplantation.
AB  - The aim of our study was to evaluate the efficacy of FK506, mycophenolate mofetil
      (MM) and aminoguanidine (AMG) on infiltration of macrophages (MPHs), neutrophils
      (NPHs) and dendritic cells (DC) into corneal grafts during the early phases after
      transplantation (Tx). Tx was performed in mice (C57BL/10 to BALB/c). Therapy
      included FK506 (0.2 mg/kg), MM (30 mg/kg) or AMG (0.1 g/kg), started at the day
      of Tx and was injected i.p. daily. Corneas were excised on the third and seventh
      day after Tx. Immunohistological evaluation using antibodies against MPHs, NPHs
      and DC was performed and corneal grafts were assessed in the periphery and in
      central part of the cornea separately. On the third day after Tx, a massive
      infiltration of MPHs and NPHs into corneal grafts was revealed; the DC
      infiltration was lower in all treated groups. Treatment with FK506 and MM led to
      a significant reduction of NPHs in the centers of the grafts, but not of MPHs. In
      contrast, AMG significantly reduced MPHs migration into allografts on the third
      day after Tx, whereas NPHs infiltration has not been attenuated. However,
      immunosuppressants had no influence on the infiltration of DC during early phases
      after Tx.

PMID- 17184146
TI  - Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected
      adipose tissue-derived hormones in obese women with type 2 diabetes.
AB  - PPAR-alpha agonists improve insulin sensitivity in rodent models of
      obesity/insulin resistance, but their effects on insulin sensitivity in humans
      are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic
      clamp in 10 obese females with type 2 diabetes before and after three months of
      treatment with PPAR-alpha agonist fenofibrate and studied the possible role of
      the changes in endocrine function of adipose tissue in the metabolic effects of
      fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated
      hemoglobin and atherogenic index were significantly elevated in obese women with
      type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were
      significantly lower than in the control group (n=10). No differences were found
      in serum resistin levels between obese and control group. Fenofibrate treatment
      decreased serum triglyceride concentrations, while both blood glucose and
      glycated hemoglobin increased after three months of fenofibrate administration.
      Serum adiponectin or resistin concentrations were not significantly affected by
      fenofibrate treatment. All parameters of insulin sensitivity as measured by
      hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic
      group compared to the control group before treatment and were not affected by
      fenofibrate administration. We conclude that administration of PPAR-alpha agonist
      fenofibrate for three months did not significantly affect insulin sensitivity or
      resistin and adiponectin concentrations in obese subjects with type 2 diabetes
      mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans
      relative to rodents could be due to a generally lower PPAR-alpha expression in
      human liver and muscle.

PMID- 17184147
TI  - Effect of monosodium glutamate on apoptosis and Bcl-2/Bax protein level in rat
      thymocyte culture.
AB  - Monosodium glutamate (MSG), the sodium salt of glutamate, is commonly used as a
      flavor enhancer in modern nutrition. Recent studies have shown the existence of
      glutamate receptors on lymphocytes, thymocytes and thymic stromal cells. In this
      study, we evaluated the in vitro effect of different MSG concentrations on rat
      thymocyte apoptosis and expression of two apoptosis-related proteins, Bcl-2 and
      Bax. Rat thymocytes, obtained from male Wistar rats, were exposed to increasing
      concentrations of MSG (ranging from 1 mM to 100 mM) for 24 h. Apoptosis was
      detected using the Annexin V-FITC/PI apoptosis detection kit and cells were
      analyzed using a flow cytometer. Expression of Bcl-2 and Bax proteins were
      determined with flow cytometry using respective monoclonal antibodies. Exposure
      to MSG resulted in a dose-dependent decrease in cell survival (as determined by
      trypan blue exclusion method). Annexin V-FITC/PI also confirmed that MSG
      increased, in a dose-dependent manner, apoptotic cell death in rat thymocyte
      cultures. MSG treatment induced downregulation of Bcl-2 protein, while Bax
      protein levels were not significantly changed. Our data showed that MSG
      significantly modulates thymocyte apoptosis rate in cultures. The temporal
      profile of Bcl-2 and Bax expression after MSG treatment suggests that
      downregulation of Bcl-2 protein and the resulting change of Bcl-2/Bax protein
      ratio may be an important event in thymocyte apoptosis triggered by MSG.

PMID- 17184148
TI  - Intracellular mediators in regulation of leptin secretion from adipocytes.
AB  - Leptin is a hormone primarily secreted by adipocytes and participating in the
      regulation of food intake and energy expenditure. Its blood levels usually
      correlate with adiposity. The secretion of this hormone is affected, among
      others, by food consumption, insulin, fasting and cold exposure. Regulation of
      leptin secretion depends on many intracellular events. It is known that the
      activation of mTOR (the mammalian target of rapamycin) as well as increase in ATP
      and malonyl-CoA content in adipocytes enhance secretion of leptin. The rise in
      intracellular cAMP and fatty acids is thought to evoke the opposite effect.
      Moreover, the undisturbed action of endogenous adenosine in adipocytes and the
      proper intracellular Ca(2+) concentration in these cells were also found to have
      an important function in leptin release. The role of mTOR, ATP, cAMP, fatty
      acids, malonyl-CoA, adenosine and Ca(2+) in the regulation of leptin secretion
      from adipocytes is discussed.

PMID- 17184150
TI  - Responsiveness and habituation of soluble ICAM-1 to acute psychosocial stress in
      men: determinants and effect of stress-hemoconcentration.
AB  - We studied the psychophysiology of soluble intercellular adhesion molecule-1
      (sICAM-1) in 25 apparently healthy middle-aged men who underwent an acute
      psychosocial stressor three times with one week apart. Measures of the biological
      stress response were obtained at week one and three. The magnitude of the sICAM-1
      stress response showed no habituation between individual visits. At week one,
      cognitive stress appraisal independently predicted integrated sICAM-1 area under
      the curve (AUC) between rest, immediately post-stress, and 45 min and 105 min
      post-stress (beta=0.67, p=0.012, deltaR(2)=0.41). Diastolic blood pressure AUC
      (beta=-0.45, p=0.048, deltaR(2)=0.21) and heart rate AUC (beta=0.44, p=0.055,
      deltaR(2)=0.21) were independent predictors of sICAM-1 AUC at week three.
      Adjustment for hemoconcentration yielded a decrease in sICAM-1 levels from rest
      to post-stress (p<0.001). Stress responsiveness of plasma sICAM-1 was predicted
      by stress perception and hemodynamic reactivity and affected by stress
      hemoconcentration but unrelated to cortisol reactivity and not readily adapting
      to repeated stress.

PMID- 17184149
TI  - Early detection of anthracycline cardiotoxicity in a rabbit model: left ventricle
      filling pattern versus troponin T determination.
AB  - Anthracycline cardiotoxicity represents a serious risk of anticancer
      chemotherapy. The aim of the present pilot study was to compare the potential of
      both the left ventricular (LV) filling pattern evaluation and cardiac troponin T
      (cTnT) plasma levels determination for the early detection of daunorubicin
      induced cardiotoxicity in rabbits. The echocardiographic measurements of
      transmitral LV inflow as well as cTnT determinations were performed weekly for 10
      weeks in daunorubicin (3 mg/kg weekly) and control groups (n=5, each).
      Surprisingly, no significant changes in LV-filling pattern were observed through
      the study, most likely due to the xylazine-containing anesthesia, necessary for
      appropriate resolving of the E and A waves. In contrast to the echographic
      measurement, the dP/dt(min) index obtained invasively at the end of the study
      revealed a significant impairment in LV relaxation, which was further supported
      by observed disturbances in myocardial collagen content and calcium homeostasis.
      However, at the same time cTnT plasma levels were progressively rising in the
      daunorubicin-treated animals from the fifth week (0.024+/-0.008 microg/l) until
      the end of the experiment (0.186+/-0.055 microg/l). Therefore, in contrast to
      complicated non-invasive evaluation of diastolic function, cTnT is shown to be an
      early and sensitive marker of anthracycline-induced cardiotoxicity in the rabbit
      model.

PMID- 17184151
TI  - WITHDRAWN: Hypophysial hormone secretion induced by lipopolysaccharide in rats:
      Involvement of the anteroventral third ventricle region.
AB  - This paper has been withdrawn by publisher at the authors request.

PMID- 17184152
TI  - Blood pressure and heart rate variability response to noninvasive ventilation in
      patients with exacerbations of chronic obstructive pulmonary disease.
AB  - Sympathetic activation and parasympathetic withdrawal are commonly observed
      during acute exacerbations of chronic obstructive pulmonary disease (COPD). We
      have demonstrated previously that noninvasive positive-pressure ventilation
      (NPPV) improves parasympathetic neural control of heart rate in patients with
      obstructive sleep apnea. We hypothesized that NPPV may exert such beneficial
      effects in COPD as well. Therefore, we assessed the acute effects of NPPV on
      systemic blood pressure and indexes of heart rate variability (HRV) in 23
      patients with acute exacerbations of COPD. The measurements of HRV in the
      frequency domain were computed by an autoregressive spectral technique. The use
      of NPPV resulted in significant increases of oxygen saturation (from 89.2+/-1.0
      to 92.4+/-0.9 %, p<0.001) in association with reductions in systolic and
      diastolic blood pressures and heart rate (from 147+/-3 to 138+/-3 mm Hg, from
      86+/-2 to 81+/-2 mm Hg, from 85+/-3 to 75+/-2 bpm, p<0.001 for all variables),
      and increases in ln-transformed high frequency band of HRV (from 6.4+/-0.5 to
      7.4+/-0.6 ms(2)/Hz, p<0.01). Reductions in heart rate and increases in ln
      transformed HF band persisted after NPPV withdrawal. In conclusion, these
      findings suggest that NPPV may cause improvements in the neural control of heart
      rate in patients with acute exacerbations of COPD.

PMID- 17184153
TI  - Colon submucosal microdialysis: a novel in vivo approach in barrier function
      assessment - a pilot study in rats.
AB  - During shock, prognosis of a patient depends largely on intestinal barrier
      function. The potency of gut epithelium to represent an obstacle to toxins is
      determined by the blood supply. All established methods of mucosal function
      determination necessitate the functional involvement of bloodstream.
      Microdialysis allows monitoring of extracellular substances in the gut submucosa,
      but its potential use for gut barrier integrity assessment is unknown. Twelve
      rats underwent perfusion of the descending colon either with 20 % ethanol or
      control medium (vehicle). Both media contained equal amounts of a radioactive
      tracer substance ((51)Cr-EDTA). Mucosal permeability for (51)Cr-EDTA was assessed
      by microdialysate to luminal perfusate activity ratios. Sampling was performed
      using the colon submucosal microdialysis technique. The group subjected to
      ethanol treatment had profound macro- and microscopical alterations in perfused
      colonic segment associated with a significant increase in tracer permeability
      during ethanol exposure (2.354+/-0.298 % for ethanol as opposed to 0.209+/-0.102
      % for control group, p 0.01), which remained elevated for 60 min after cessation
      of ethanol administration (3.352+/-0.188 % for ethanol compared to 0.140+/-0.0838
      % for the control group, p 0.001). Submucosal microdialysis with radioactive
      tracer substance can be considered a feasible and advantageous alternative of gut
      barrier function estimation. Parallel monitoring of local tissue chemistry with
      this method remains a challenge in the future.

PMID- 17184154
TI  - Hypoxia-induced cytosine deaminase gene expression for cancer therapy.
AB  - Hypoxia, a hallmark of many solid tumors, is associated with angiogenesis and
      tumor progression. It activates a signal cascade that culminates in the
      stabilization of hypoxia-inducible factor-1 (HIF-1) transcription factor and
      activation of genes that possess hypoxia response elements. The loss of tumor
      suppressors such as p53 has been shown to stabilize HIF-1alpha, which is
      overexpressed in the majority of human cancers, and its over-expression
      correlates with poor prognosis and treatment failure. Here we constructed hypoxia
      inducible promoters and examined their activities in murine and human cancer
      cells with variable p53 status. Loss of p53 function in cancer cells resulted in
      increased HIF-1-dependent transcriptional activity. To investigate the
      feasibility of exploiting the hypoxic tumor microenvironment for targeted gene
      therapy of cancer, we constructed retroviral vectors harboring luciferase or
      Escherichia coli cytosine deaminase (CD) genes under the control of the hypoxia
      inducible promoter. Murine Lewis lung carcinoma (LL2) cells carrying defective
      p53, when retrovirally transduced with the hypoxia-inducible promoter-driven
      luciferase gene under hypoxic conditions, increased luciferase reporter gene
      expression in vitro and in vivo. Significant antitumor effects were achieved in
      mice bearing LL2 tumors that expressed CD driven by a hypoxia-inducible promoter
      after treatment with 5-fluorocytosine. These results suggest the potential
      applications of suicide genes, such as the CD gene, under the control of hypoxia
      inducible promoters for cancer gene therapy, which may target efficiently to
      hypoxic regions of tumors with p53 mutations.

PMID- 17184155
TI  - Evaluation of twenty human adenoviral types and one infectivity-enhanced
      adenovirus for the therapy of soft tissue sarcoma.
AB  - The clinical course of sarcoma warrants the development of new therapeutic
      options, such as gene therapy. However, the lack of coxsackievirus-adenovirus
      receptor (CAR) on sarcoma cells limits the efficacy of adenovirus type 5 (Ad5)
      based gene therapy. In this study we evaluated 20 different adenoviral types and
      1 Ad5 vector with RGD-containing fiber for their internalization efficiency in
      sarcoma cells. We demonstrated that adenovirus types 35, 3, 7, 11, 9, and 22 and
      Ad5lucRGD virions (ranked in descending order) have significantly higher
      internalization efficiency in the tested sarcoma cells when compared with Ad5. On
      the basis of these results we developed a conditionally replication-competent
      adenoviral vector, Ad5Delta24.Ki.COX, and compared its oncolytic efficacy with
      that of Ad5/35Delta24.Ki.COX, an Ad5-based vector with the Ad35 fiber shaft and
      knob domains. Because both vectors differed only in the fiber, we were able to
      assess whether the adenoviral type with the most efficient internalization
      resulted also in enhanced treatment efficacy. We evaluated the antineoplastic
      activity of the oncolytic adenoviral vectors alone or in combination with the
      expression of measles virus fusogenic membrane glycoproteins and/or ifosfamide.
      The findings of our xenograft model were as follows: animals that received Ad5/35
      based therapy had significantly smaller tumors than animals treated with the
      homologous Ad5-based vectors. In addition, we demonstrated that the combination
      of virotherapy, intratumoral expression of fusogenic membrane glycoproteins, and
      ifosfamide was clearly superior compared with treatment with individual
      components alone or as combinations of two components. In conclusion, Ad35-based
      vectors are promising for the treatment of sarcoma.

PMID- 17184157
TI  - Transgenic probiotica as drug delivery systems: the golden bullet?
AB  - Functional human proteins are constitutively produced in genetically modified
      bacteria that survive on human mucosal surfaces, to the benefit of the host. The
      successful Phase I clinical trial with IL-10-producing Lactococcus lactis for
      Crohn's disease has opened new avenues for the use of transgenic bacteria as
      delivery vehicles. The major advantage of this novel strategy is the avoidance of
      systemic side effects associated with conventional therapies. This methodology
      opens up an alternative method for local delivery of therapeutic proteins to
      various mucosal tissues.

PMID- 17184159
TI  - Microneedles and transdermal applications.
AB  - With the limitations of oral drug delivery and the pain and needle phobias
      associated with traditional injections, drug delivery research has focused on the
      transdermal delivery route. A formidable barrier to transdermal drug delivery is
      the stratum corneum, the superficial layer of the skin. In the last 10 years,
      microneedles were proposed as a mechanical tool to pierce through the stratum
      corneum, in order to create drug delivery channels without stimulating underlying
      pain nerves. Since then, the field of microneedles has rapidly evolved to spawn a
      plethora of potential transdermal applications. In this review, the authors
      provide an overview of the progress in microneedle research and design, and the
      advancements that have been made in employing this technology for transdermal
      applications.

PMID- 17184158
TI  - Polymeric nanogel formulations of nucleoside analogs.
AB  - Nanogels are colloidal microgel carriers that have been recently introduced as a
      prospective drug delivery system for nucleotide therapeutics. The crosslinked
      protonated polymer network of nanogels binds oppositely charged drug molecules,
      encapsulating them into submicron particles with a core-shell structure. The
      nanogel network also provides a suitable template for chemical engineering,
      surface modification and vectorisation. This review reveals recent attempts to
      develop novel drug formulations of nanogels with antiviral and antiproliferative
      nucleoside analogs in the active form of 5'-triphosphates, discusses structural
      approaches to the optimisation of nanogel properties, and discusses the
      development of targeted nanogel drug formulations for systemic administration.
      Notably, nanogels can improve the CNS penetration of nucleoside analogs that are
      otherwise restricted from passing across the blood-brain barrier. The latest
      findings reviewed here demonstrate an efficient intracellular release of
      nucleoside analogs, encouraging further applications of nanogel carriers for
      targeted drug delivery.

PMID- 17184160
TI  - Focused ultrasound for blood-brain disruption and delivery of therapeutic
      molecules into the brain.
AB  - Noninvasive, transient and local image-guided blood-brain barrier disruption can
      be accomplished using focused ultrasound exposure with intravascular injection of
      preformed microbubbles. MRI-guided blood-brain barrier disruption has been
      demonstrated and has been shown to heal in within a few hours after exposure. The
      delivery of several marker molecules has been demonstrated in different animal
      models with minimal or no damage to the brain tissue. Most notably, the delivery
      of antibodies and liposomal doxorubicin has been shown. The method may
      potentially open a new era in CNS drug delivery and perhaps also aid in molecular
      imaging and targeting. However, effective clinical devices and methods need to be
      developed further and the clinical feasibility demonstrated.

PMID- 17184161
TI  - Paediatric and geriatric drug delivery.
AB  - Age-adapted drug formulations are a challenge in drug development. This paper
      describes the special requirements of paediatric and geriatric patients, and new
      ideas to solve the most prominent problems in the application of drugs to these
      patients. Most requirements are very similar in each subpopulation, but there are
      also some particularities. In neonates and infants, the immaturity of enzymes may
      determine the pharmacokinetics of the excipients, which must be carefully
      selected. Pharmacokinetics in the elderly are strongly influenced by co
      morbidity, multiple-drug use or reduced organ functions. The drug handling and
      the readability of the product information are key issues in both subpopulations.
      Children and the elderly show difficulties in swallowing solid dosage forms for
      oral use. In both patient groups, small sized particulates or liquid dosage forms
      are superior to classic tablets or capsules. The main problem with using liquids
      is the palatability of the solution, especially when considering that taste
      sensation differs age-dependently and interindividually. Recent technological
      developments such as the dose sipping technology, promise improvements. The new
      EU legislation for the development of new paediatric drugs may also stimulate the
      research into drug delivery for the elderly.

PMID- 17184162
TI  - Effective inhaled drug administration to mechanically ventilated patients.
AB  - Inhaled therapy is commonly employed in mechanically ventilated patients with
      chronic obstructive pulmonary disease or asthma. The efficacy of inhaled drugs is
      comparable to that achieved with systemic routes of administration, but the dose
      of drug required to achieve a therapeutic effect is generally much smaller.
      Moreover, limited systemic absorption of inhaled drugs minimises systemic side
      effects. Aerosol administration to ventilated patients differs from that in
      ambulatory patients in several respects. Optimal techniques for using pressurised
      metered-dose inhalers and nebulisers in ventilator circuits have been developed.
      With these techniques, the efficiency of inhaled drug delivery in mechanically
      ventilated patients is now comparable to that in ambulatory patients. Pressurised
      metered-dose inhalers are chiefly used to deliver bronchodilator and
      corticosteroid aerosols, and are more efficient and convenient to use than
      nebulisers for routine therapy in ventilated patients. However, nebulisers are
      more versatile and are employed to generate aerosols of bronchodilators,
      corticosteroids, antibiotics, prostaglandins, surfactant and mucolytic agents.
      Improvements in drug formulations and the design and efficiency of aerosol
      generating devices have led to increasing application of inhaled therapies in
      mechanically ventilated patients.

PMID- 17184163
TI  - First approved inhaled insulin therapy for diabetes mellitus.
AB  - The long-term benefits of tight glycemic control in preventing microvascular and
      macrovascular complications are well established in both Type 1 diabetes mellitus
      (Type 1 DM) and Type 2 diabetes mellitus (Type 2 DM). Nonetheless, achievement of
      recommended haemoglobin A1c (HbA(1c)) goals (< or = 6.5 - 7.0%) has remained
      elusive, especially in patients with diabetes who require insulin therapy.
      Delayed/suboptimal titration of insulin is partly related to poor acceptance of
      multiple injection regimen by both physicians and patients. EXUBERA (human
      insulin [rDNA origin]; Pfizer), the first approved inhaled insulin for the
      treatment of diabetic patients, has been shown to be safe and as effective as
      regular/rapidly acting insulin in improving glycemic control. In addition to
      controlling postprandial glucose excursions, EXUBERA exerts a major action to
      reduce fasting plasma glucose (FPG) concentration. Thus, it has the potential to
      be used as a monotherapy in Type 2 DM, as well as in combination with an insulin
      sensitizer in Type 2 DM or in combination with long-acting insulin in both Type 2
      DM and Type 1 DM.

PMID- 17184164
TI  - 2nd Ophthalmic Drug Development and Delivery Summit.
AB  - The Second Annual Ophthalmic Drug Development and Delivery Summit was held on 19 
      20 September 2006 in San Diego, CA, US. The 2-day symposium, having a highly
      focused theme, was packed with cutting-edge science, insightful overviews and
      networking opportunities. With a total of 11 recognized specialists presenting
      reviews and recent results in the advancement of ocular drug development and
      delivery, the invited expert speaking faculty presented the latest preclinical
      and clinical developments in novel ophthalmic therapies and drug delivery
      technology. The talks included various case studies from primary investigators
      and pharmaceutical companies touching upon key topics: updates on current
      clinical trials, study design issues, sustained delivery to the eye, views of the
      vitreous space as a drug reservoir, new developments in dry and wet age-related
      macular degeneration and diabetic retinopathy, formulation for optimal drug
      delivery, differences and similarities in developing drugs for the eye compared
      with other targets, pharmacokinetics, novel ocular delivery methods and devices,
      delivery of proteins and peptides, focal drug delivery, non-invasive drug
      delivery to the eye, neuroprotection challenges, in vitro and in vivo models for
      glaucoma and angiogenesis for early efficacy estimation, and toxicology. Overall,
      the 2-day annual symposium continues to grow as an efficient platform for
      fostering discussion on a range of scientific topics and challenges and avenues
      for building collaborative partnerships in ophthalmic drug development.

PMID- 17184166
TI  - Genes and genius: the inheritance of Gregor Mendel.

PMID- 17184167
TI  - A self-augmenting gene expression cassette for enhanced and sustained transgene
      expression in the presence of proinflammatory cytokines.
AB  - Viral promoters can yield high gene expression levels yet tend to be attenuated
      in vivo by host proinflammatory cytokines. Prolonged transgene expression can be
      obtained using constitutive cellular promoters. However, levels of transgene
      expression driven by cellular promoters are insufficient for effective therapy.
      We designed a novel self-augmenting gene expression cassette in which the
      transgene product can induce an endogenous transcription factor to enhance the
      activity of a weak cellular promoter driving its expression. Using the cellular
      major histocompatibility complex class I (H-2K(b)) promoter to drive the
      interferon (IFN-gamma) cytokine gene, we show that the H-2K(b) promoter, although
      exhibiting much lower basal activity, yields higher IFN-gamma production than the
      CMV promoter 2 days after transfection. IFN-gamma expression driven by the H
      2K(b) promoter also lasts longer than that driven by the cytomegalovirus
      promoter. Our data demonstrate that the self-augmenting strategy provides a
      promising approach to achieve high and sustained transgene expression in vivo.

PMID- 17184168
TI  - Baculovirus surface display of SARS coronavirus (SARS-CoV) spike protein and
      immunogenicity of the displayed protein in mice models.
AB  - The baculovirus surface display technique has provided an ideal tool to display
      foreign proteins with natural conformation, functions, and immunogenicity. In
      this work, we explored the application of this technique on SARS-associated
      coronavirus (SARS-CoV) spike (S) protein, and further analyzed the immunogenicity
      of displayed S protein. The entire ectodomain of S protein was fused between the
      gp64 signal peptide and the VSV-G membrane anchor and successfully displayed on
      the baculovirus surface. Subcutaneous injection with purified S-displayed
      baculoviruses without adjuvant elicited highly effective production of specific
      and neutralizing antibodies against S protein in mice. These results confirmed a
      successful surface display of S protein on baculoviruse, and suggested a
      potential role of S-displayed baculoviruses as a novel live virus-based vaccine
      candidate for SARS-CoV.

PMID- 17184169
TI  - A positive involvement of RecQL4 in UV-induced S-phase arrest.
AB  - RecQL4 belongs to a family of conserved RECQ helicases that are important in
      maintaining chromosomal integrity. Human patients lacking RecQL4 showed extreme
      sensitivity to UV and oxidation damage, suggesting that RecQL4 is involved in the
      damage signaling and/or repair. Here we show that human mutant cells lacking
      RecQL4 were defective in UV-induced S-phase arrest, whereas cells defective in
      bloom syndrome protein (BLM), another member of RecQ family exhibited a normal S
      phase arrest following UV irradiation. In keeping with this, a targeted
      inhibition of RecQL4 expression in human 293 cells showed a defect in inducing S
      phase (replication) arrest following UV treatment. Human mutant cells lacking
      RecQL4 protein were also defective in inducing S-phase arrest following
      hydroxyurea treatment. Together, our results suggest that RecQL4 may have a
      unique role in replication fork arrest, which may not be shared with other
      members of RecQ family such as BLM.

PMID- 17184170
TI  - Nitrosative stress and pathogenesis of insulin resistance.
AB  - Insulin resistance is a major causative factor for type 2 diabetes and is
      associated with increased risk of cardiovascular disease. Despite intense
      investigation for a number of years, molecular mechanisms underlying insulin
      resistance remain to be determined. Recently, chronic inflammation has been
      highlighted as a culprit for obesity-induced insulin resistance. Nonetheless,
      upstream regulators and downstream effectors of chronic inflammation in insulin
      resistance remain unclarified. Inducible nitric oxide synthase (iNOS), a mediator
      of inflammation, has emerged as an important player in insulin resistance.
      Obesity is associated with increased iNOS expression in insulin-sensitive tissues
      in rodents and humans. Inhibition of iNOS ameliorates obesity-induced insulin
      resistance. However, molecular mechanisms by which iNOS mediates insulin
      resistance remain largely unknown. Protein S-nitrosylation, a covalent attachment
      of NO moiety to thiol sulfhydryls, has emerged as a major mediator of a broad
      array of NO actions. S-nitrosylation is elevated in patients with type 2
      diabetes, and increased S-nitrosylation of insulin signaling molecules, including
      insulin receptor, insulin receptor substrate-1, and Akt/PKB, has been shown in
      skeletal muscle of obese, diabetic mice. Akt/PKB is reversibly inactivated by S
      nitrosylation. Based on these findings, S-nitrosylation has recently been
      proposed to play an important role in the pathogenesis of insulin resistance.

PMID- 17184171
TI  - Effects of PGC-1alpha on TNF-alpha-induced MCP-1 and VCAM-1 expression and NF
      kappaB activation in human aortic smooth muscle and endothelial cells.
AB  - Increased oxidative stress in vascular cells is implicated in the pathogenesis of
      atherosclerosis. Reactive oxygen species (ROS) induce vascular inflammation via
      the proinflammatory cytokine/NF-kappaB pathway. Several lines of evidence suggest
      that peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC
      1alpha) is an important regulator of intracellular ROS levels. However, no
      studies have examined the effects of PGC-1alpha on this process. We investigated
      the effects of PGC-1alpha on inflammatory molecule expression and activity of the
      redox-sensitive transcription factor, NF-kappaB, in vascular cells. PGC-1alpha
      expressed in human aortic smooth (HASMCs) and endothelial cells (HAECs) is
      upregulated by AMP-activated protein kinase activators, including metformin,
      rosiglitazone and alpha-lipoic acid. Tumor necrosis factor-alpha (TNF-alpha), a
      major proinflammatory factor in the development of vascular inflammation,
      stimulates intracellular ROS production through an increase in both mitochondrial
      ROS and NAD(P)H oxidase activity. Adenovirus-mediated overexpression of the PGC
      1alpha gene in HASMCs and HAECs leads to a significant reduction in intracellular
      and mitochondrial ROS production as well as NAD(P)H oxidase activity.
      Consequently, NF-kappaB activity and MCP-1 and VCAM-1 induced by TNF-alpha are
      suppressed. Our data support the possibility that agents stimulating PGC-1alpha
      expression in the vasculature aid in preventing the development of
      atherosclerosis.

PMID- 17184172
TI  - A high glycolytic flux supports the proliferative potential of murine embryonic
      stem cells.
AB  - Embryonic stem (ES) cells are immortal and present the ability to self-renew
      while retaining their ability to differentiate. In contrast, most primary cells
      possess a limited proliferative potential, and when this is exhausted, undergo an
      irreversible growth arrest termed senescence. In primary cells, senescence can be
      also triggered by a variety of stress to which ES cells are highly refractory.
      Here the authors report that the proliferative capacity of murine ES cells
      closely correlates with high activity of different glycolytic enzymes, elevated
      glycolytic flux, and low mitochondrial oxygen consumption. The direct relation
      between glycolytic flux and the ability of ES cells to proliferate is further
      remarked in experiments where glycolysis or ES cell self-renewal was specifically
      inhibited. It was previously reported that the upregulation of glycolysis in
      primary cells results in life span extension. The authors hypothesize that the
      naturally high glycolytic flux observed in murine ES cells can be responsible for
      their unlimited proliferative potential.

PMID- 17184173
TI  - Mitochondrial complex I inhibition in Parkinson's disease: how can curcumin
      protect mitochondria?
AB  - Selective damage of mitochondrial complex I within the dopaminergic neurons of
      the substantia nigra is the central event during Parkinson disease. Peroxynitrite
      is one of the important free radicals probably mediating complex I damage.
      Peroxynitrite inhibits brain complex I mainly by 3-nitrotyrosine and nitrosothiol
      formation, but how these modifications alter the structure-function relation of
      complex I is unclear. Curcumin pretreatment protects brain mitochondria against
      peroxynitrite in vitro by direct detoxification and prevention of 3-nitrotyrosine
      formation and in vivo by elevation of total cellular glutathione levels. These
      results suggest a potential therapeutic role for curcumin against nitrosative
      stress in neurological disorders.

PMID- 17184174
TI  - Deferoxamine lowers tissue damage after 80% exchange transfusion with polymerized
      hemoglobin.
AB  - Hemoglobin (Hb) solutions have been proposed as potential substitutes for
      erythrocytes to maintain oxygen-carrying capacity in situations in which blood is
      not available. This study investigated systemic and microvascular hemodynamics as
      well as tissue oxygenation and viability after an 80% exchange transfusion with
      an oxygen-carrying blood substitute based on polymerized bovine hemoglobin (PBH).
      Studies were carried in unanesthetized hamsters prepared with a window-chamber
      model for microcirculation evaluation. Heme iron-mediated injury to the tissue
      was analyzed by using deferoxamine (an iron chelator), which reduces free iron
      toxicity. Exchange transfusion led to a significant decrease in hematocrit (Hct)
      and an increase in plasma Hb, in addition to a significant decrease of arteriolar
      and venular diameters, flow velocity, and, therefore, microvascular blood flow.
      Capillary perfusion was severely compromised after exchange, but tissue pO2
      increased above baseline, and oxygen extraction was reduced. Apoptotic and
      necrotic cells increased significantly after the exchange; however, this effect
      was only partially due to the toxicity of free iron. Iron therapy decreased the
      microvascular and oxygenation changes but did not fully reverse the adverse
      effects. Assessment of tissue viability after exchange suggests that chelation
      treatment in cases of large exchange transfusions with acellular Hb could be
      potentially beneficial.

PMID- 17184175
TI  - Glycemic control of apoptosis in the pancreatic beta cell: danger of extremes?
AB  - Excessive formation of oxygen radicals is a well-established mediator of
      hyperglycemic damage in diabetes to a wide range of tissues, such as neurons,
      retinal cells, and vascular endothelium. Increased oxygen radical formation is
      generally considered a toxic side effect of excessive rates of mitochondrial
      oxidative metabolism and electron transport in high glucose-exposed cells. Along
      the same line, metabolic oxidative stress is currently also regarded as crucial
      mediator of beta cell dysfunction and apoptosis under hyperglycemic conditions.
      Here the authors argue that a healthy beta cell is well equipped to deal
      adequately with elevated glucose metabolic rates, and demonstrate that decreased
      glucose catabolism leads to ROS production and apoptosis. They therefore propose
      that adverse metabolic conditions in poorly controlled diabetes (hyperglycemia
      and/or dyslipidemia) or genetic defects could decrease the viability of beta
      cells by interfering with normal glucose sensing and metabolism, rather than by
      overactivating it. This view is supported by the fragmentary data currently
      available on the pathways for hypergycemic and hypoglycemic beta cell death.

PMID- 17184176
TI  - Is SS-A/Ro52 a hydrogen peroxide-sensitive signaling molecule?
AB  - SS-A/Ro52 (Ro52) protein is one of the targets of autoantibodies in Sjogren's
      syndrome and systemic lupus erythematosus. Ro52 structurally belongs to the RING
      B-box/coiled-coil family, which appears to carry out diverse functions, but the
      physiological function of Ro52 remains largely unknown. Here, the authors
      demonstrate that hydrogen peroxide but not other oxidative stressors induced
      translocation of Ro52 protein from the cytoplasm to the nucleus and this
      phenomenon was attenuated by inhibition of MAP kinases, ERK in particular. These
      findings raise the possibility that SS-A/Ro52 may function as a hydrogen peroxide
      selective, oxidative stress-sensitive signaling molecule that is activated via
      the MAP kinase pathway.

PMID- 17184177
TI  - Impact of mitochondrial ROS production in the pathogenesis of diabetes mellitus
      and its complications.
AB  - In this review, the impacts of mitochondrial reactive oxygen species (ROS) on
      diabetes and its complications are described. In endothelial cells, high-glucose
      treatment increases mitochondrial ROS and normalization of the ROS production by
      inhibitors of mitochondrial metabolism, or by overexpression of UCP-1 or MnSOD,
      prevents glucose-induced activation of PKC, formation of AGE, and accumulation of
      sorbitol, all of which are believed to be the main molecular mechanisms of
      diabetic complications. Glomerular hyperfiltration, one of the characteristics of
      early diabetic nephropathy, may be caused by mitochondrial ROS through activation
      of COX-2 gene transcription, followed by PGE2 overproduction. In pancreatic beta
      cells, hyperglycemia also increases mitochondrial ROS, which suppresses the first
      phase of glucose-induced insulin secretion, at least in part, through the
      suppression of GAPDH activity. In liver cells, similar to that in hyperglycemia,
      TNF-alpha increases mitochondrial ROS, which in turn activates apoptosis signal
      regulating kinase 1 (ASK1) and c-jun NH2-terminal kinases (JNK), increases serine
      phosphorylation of IRS-1, and decreases insulin-stimulated tyrosine
      phosphorylation of IRS-1, leading to insulin resistance. These results suggest
      the importance of mitochondrial ROS in the pathogenesis of diabetes mellitus and
      its complications through modification of various cellular events in many
      tissues, including vessels, kidney, pancreatic beta cells, and liver.

PMID- 17184179
TI  - Metabolic disorders in diabetes mellitus: impact of mitochondrial function and
      oxidative stress on diabetes and its complications.

PMID- 17184178
TI  - Are free radical reactions increased in the diabetic eye?
AB  - Reactive oxygen species (ROS) are thought to play a significant role in the
      development of diabetic retinopathy; however, no direct evidence supports ROS
      generation in vivo. This study used in vivo electron spin resonance (ESR)
      spectroscopy with a surface resonator to detect local free radical reactions. The
      ESR signal decay of carbamoyl-PROXYL was enhanced in the eyes of streptozotocin
      (STZ)-induced diabetic mice. This enhanced signal decay was suppressed by the
      administration of SOD or the pretreatment with aminoguanidine. We demonstrate,
      for the first time, specific free radical reactions in the eyes of mice with STZ
      induced diabetes.

PMID- 17184180
TI  - Lisinopril as an antioxidant in hypertension?
AB  - Lisinopril is an inhibitor of the renin-angiotensin system. Does lisinopril
      minimize oxidative damage in spontaneously hypertensive rats (SHR) in comparison
      with the normotensive genetic controls Wistar Kyoto (WKY)? The authors note that
      lisinopril contained lipid peroxidation, elevated tissue glutathione levels, and
      influenced the activity of antioxidant enzymes such as catalase and glutathione
      peroxidase. Studies in humans testing the hypothesis that lisinopril has
      antioxidant function in vivo are warranted.

PMID- 17184181
TI  - Involvement of oxidative stress in the pathogenesis of diabetes.
AB  - Pancreatic beta-cell failure is the common characteristic of type 1 and type 2
      diabetes. Type 1 diabetes is induced by pancreatic beta-cell destruction, which
      is mediated by an autoimmune mechanism and consequent inflammatory process.
      Various inflammatory cytokines and oxidative stress produced by islet
      infiltrating immune cells have been proposed to play an important role in
      mediating the destruction of beta cells. The JNK pathway is also activated by
      such cytokines and oxidative stress and is involved in beta-cell destruction.
      Type 2 diabetes is the most prevalent and serious metabolic disease affecting
      people all over the world. Pancreatic beta-cell dysfunction and insulin
      resistance are the hallmark of type 2 diabetes. Once hyperglycemia becomes
      apparent, beta-cell function gradually deteriorates, and insulin resistance is
      aggravated. This process is called "glucose toxicity." Under such conditions,
      oxidative stress is provoked, and the JNK pathway is activated, which is likely
      involved in pancreatic beta-cell dysfunction and insulin resistance. In addition,
      oxidative stress and activation of the JNK pathway are involved in the
      progression of atherosclerosis, which is often observed under diabetic
      conditions. Taken together, it is likely that oxidative stress and subsequent
      activation of the JNK pathway are involved in the pathogenesis of type 1 and type
      2 diabetes.

PMID- 17184182
TI  - Renal microvascular injury in diabetes: RAGE and redox signaling.
AB  - Diabetic nephropathy remains a major cause of morbidity and mortality in the
      diabetic population and is the leading cause of end-stage renal failure in the
      Western World. Despite current therapeutics including intensified glycemic
      control and blood pressure lowering agents, renal disease continues to progress
      relentlessly in diabetic patients, albeit at a lower rate. It is well recognized
      that metabolic and hemodynamic factors play a central role in accelerating renal
      disease in diabetes. However, recent experimental studies have suggested that
      increased generation of reactive oxygen species (ROS) as a result of the diabetic
      milieu may play a central role in the progression of diabetic microvascular
      complications. These ROS appear to be generated primarily from mitochondrial
      sources and via the enzyme, NADPH oxidase. This review focuses on how ROS play a
      deleterious role in the diabetic kidney and how they are involved in crosstalk
      among various signaling pathways, ultimately leading to renal dysfunction and
      structural injury.

PMID- 17184183
TI  - Orthostatic hypotension and autonomic pathways after spinal cord injury.
AB  - Individuals with spinal cord injury (SCI) are prone to orthostatic hypotension
      (OH). We aimed to develop a simple bedside test to evaluate autonomic control
      following chronic SCI, and to identify those most at risk of OH and
      cardiovascular dysfunction. We studied 14 subjects with cervical SCI, 11 with
      thoracic SCI, and 17 able-bodied controls. We continuously recorded heart rate
      (HR; ECG) and beat-to-beat systolic (SAP), diastolic (DAP) and mean (MAP)
      arterial pressures (Finometer) while supine, and following the passive assumption
      of an upright seated position. Stroke volume (SV), cardiac output (CO), and total
      peripheral resistance (TPR) were calculated. Plasma catecholamines were
      determined. Motor and sensory loss was assessed using the American Spinal Injury
      Association (ASIA) impairment scale. Autonomic pathways were assessed from
      sympathetic skin responses (SSR). Cervical SCI subjects had lower supine HR, SAP,
      and noradrenaline levels than thoracic SCI and controls (p < 0.05), and lower DAP
      and MAP than controls (p < 0.05). When upright, HR increased in all groups (p <
      0.05); SAP, DAP, and MAP increased (p < 0.01) in thoracic SCI and controls, but
      not in cervical SCI. Cervical SCI had larger postural falls in SV (p < 0.05) and
      CO, with smaller increases in TPR than the other two groups. Upright
      catecholamine levels were lower in cervical SCI (p < 0.05) than thoracic SCI and
      controls. Completeness of SCI assessed by ASIA scale did not necessarily
      correlate with autonomic completeness assessed by SSR. Cardiovascular control
      during orthostasis was impaired and OH was common in cervical SCI, but not
      thoracic SCI. SSR may identify those at greatest risk of orthostatic hypotension
      and impaired cardiovascular control. We advocate that assessments of autonomic
      function be included in the neurological evaluation of SCI, in addition to the
      ASIA assessment.

PMID- 17184184
TI  - Phenotypic changes in NG2+ cells after spinal cord injury.
AB  - Following contusive spinal cord injury (SCI), 50% of oligodendrocytes in the
      residual white matter are lost within 24 h. NG2-expressing cell proliferation is
      maximal 3 days after SCI, and may be the source of mature oligodendrocytes and
      astrocytes that chronically replace those that were lost. We studied NG2(+) cells
      dissociated from the 3-day injured spinal cord for comparison with those from
      uninjured adult and early postnatal cords. After 24 h in serum-containing medium,
      we performed patch clamp analysis and immunocytochemistry for NG2 in combination
      with nestin (progenitors), and A2B5, O4, and O1 (oligodendrocyte lineage
      markers). We observed an NG2(+)/A2B5-/O4-/O1- population in both adult
      preparations. More than double the normal number of NG2(+) cells was isolated
      from the injured cord, but OX42(+) microglia/macrophages were the predominant
      cell type after injury. Most cells isolated at P7 were NG2-/A2B5(+), whereas
      those from the normal adult were NG2(+)/A2B5-. NG2(+) cells after SCI displayed
      altered voltage-gated potassium current profiles compared to normal adult and P7
      animals. Additionally, less than 25% of adult cells (normal and injured)
      responded to GABA and glutamate, compared to 100% of P7 cells. Our results
      indicate that the adult NG2(+) cell pool is antigenically and physiologically
      different than the early postnatal pool, and that contusive injury induces
      changes in adult NG2(+) cells.

PMID- 17184185
TI  - Role of prostacyclin in the development of compression trauma-induced spinal cord
      injury in rats.
AB  - We investigated the role of prostacyclin (PGI(2)) in the development of
      compression trauma-induced spinal cord injury (SCI) in rats. When measured after
      induction of SCI, tissue levels of 6-keto-PGF(1), a stable PGI(2) metabolite,
      thromboxane B(2) (TXB(2)), a stable metabolite of thromboxane A(2),
      myeloperoxidase (MPO) activity, and tumor necrosis factor (TNF) in the injured
      spinal cord segment were significantly increased, peaking at 2, 3, and 4 h after
      induction of SCI, respectively. Subcutaneous administration of indomethacin (IM),
      a non-selective cyclooxygenase (COX) inhibitor, completely inhibited increases in
      tissue levels of 6-keto-PGF(1) and TXB(2), while administration of NS-398, a
      selective inhibitor of COX-2, did not affect these increases. Although
      pretreatment with IM enhanced increases in tissue levels of MPO, TNF, and TNF
      mRNA and exacerbated both motor disturbances and histological damage in the
      spinal cord of animals subjected to SCI, pretreatment with NS-398 had no effect
      on any of these findings. Both iloprost, a stable analog of PGI(2), and leukocyte
      depletion significantly reversed changes in various variables and exacerbation of
      motor disturbances induced by IM pretreatment in animals subjected to SCI. These
      observations strongly suggested that compression trauma-induced increase in
      PGI(2) production in spinal cord tissue might be mainly mediated by COX-1 and
      PGI(2) might play a critical role in reduction of motor disturbances following
      SCI by inhibiting neutrophil accumulation through inhibition of TNF production.

PMID- 17184186
TI  - Transplantation of fibroblasts that overexpress matrix metalloproteinase-3 into
      the site of spinal cord injury in rats.
AB  - Growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) are upregulated
      during glial scar formation at the site of spinal cord injury (SCI) in adult
      mammals. This CSPG-containing glial scar inhibits axonal regeneration. Matrix
      metalloproteinases (MMPs) can degrade CSPGs and other inhibitory proteins to
      promote neurite outgrowth. Increased MMP synthesis and secretion are observed in
      fibroblasts adjacent to tumor cells that express the protein EMMPRIN
      (Extracellular Matrix MetalloPRoteinase INducer). EMMPRIN transduction of cells
      provides an avenue to deliver increased levels of MMPs to the site of SCI in a
      sustained, localized, and moderate fashion. We explored the use of EMMPRIN
      transduced cells as a mechanism to degrade CSPGs, facilitate axonal growth and
      improve recovery after SCI. Human dermal fibroblasts infected with a recombinant
      EMMPRIN adenovirus significantly increased secretion of MMP-3 compared to
      fibroblasts infected with a control adenovirus. Decreased CSPG immunoreactivity
      was observed in injured spinal cord sections when they were incubated with media
      from EMMPRIN-transduced fibroblasts. Conditioned media from EMMPRIN-transduced
      fibroblasts increased the length of neurites that were grown on a CSPG substrate.
      Rats that received contusive SCI and EMMPRIN-transduced fibroblast transplants
      demonstrated improved locomotor recovery compared to rats that received control
      fibroblasts, but not compared to other control groups. EMMPRIN-transplanted rats
      showed a significant increase in the number of retrogradely labeled cell bodies
      within brainstem nuclei and an increase in serotonergic fibers distal to the site
      of injury. EMMPRIN, and consequently MMP, delivery to the injured spinal cord may
      prove to be beneficial in reducing some of the physical barriers to axonal growth
      after SCI.

PMID- 17184187
TI  - Mn (III) tetrakis (4-benzoic acid) porphyrin administered into the intrathecal
      space reduces oxidative damage and neuron death after spinal cord injury: a
      comparison with methylprednisolone.
AB  - The metalloporphyrin Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) is a
      cell-permeable superoxide dismutase mimetic and a broad-spectrum scavenger of
      reactive species. Since MnTBAP may not cross the blood-brain barrier, this study
      evaluated the therapeutic potential of MnTBAP to treat spinal cord injury (SCI;
      25 g x cm) by directly administering it into the intrathecal space of the rat
      spinal cord. The cells in spinal sections removed at 24 h post-SCI were
      immunohistochemically stained with anti-4-hydroxynonenal (HNE), a marker of
      membrane lipid peroxidation (MLP); anti-nitrotyrosine (Ntyr), a marker of protein
      nitration; and anti-neuron-specific enolase (NSE) antibodies. Immunostained
      neurons were counted for quantitative evaluation. Pre-treatment 30 min before SCI
      with 1 mg/kg MnTBAP or 4-h post-SCI treatment with 2.5 mg/kg MnTBAP administered
      into the intrathecal space significantly reduced MLP and protein nitration, and
      increased the number of surviving neurons compared to vehicle controls. However,
      post-SCI treatment with a standard regimen of methylprednisolone sodium succinate
      (MPSS; 30 mg/kg followed by 5.4 mg/kg for maintenance, iv administration), the
      only drug used for clinical treatment of SCI, not only did not reduce MLP and
      neuron loss, it increased protein nitration compared with vehicle controls (two
      way analysis of variance [ANOVA] followed by the Tukey test). These results
      demonstrate that pre- and post-intrathecal treatments with the low doses of
      MnTBAP provide sustained neuroprotection by preventing oxidative stress and that
      post-treatment with MnTBAP is superior to post-treatment with MPSS in preventing
      oxidative stress and resulting neuron loss.

PMID- 17184188
TI  - Nitric oxide reversibly impairs axonal conduction in Guinea pig spinal cord.
AB  - Increased expression of the inducible and neuronal isoforms of nitric oxide
      synthase (NOS), and elevated concentrations of nitric oxide (NO) metabolites, are
      present within the central nervous system (CNS) following neurotrauma and are
      implicated in the pathogenesis of the accompanying neurologic deficits. We tested
      the hypothesis that elevated extracellular concentrations of NO introduced by the
      donor Spermine NONOate, induce reversible axonal conduction deficits in neurons
      of the guinea pig spinal cord. The compound action potential (CAP) and compound
      membrane potential (CMP) of excised ventral cord white matter were recorded
      before, during, and after bathing the tissue (30 min) in varying concentrations
      (0.25-3.0 mM) of Spermine NONOate. The principal results were a rapid onset, dose
      dependent, reduction in amplitude of the CAP (p < 0.05) accompanied by
      depolarization of the CMP during NO exposure. These effects were largely
      reversible on washout, at low concentration of the donor (0.5 mM), but were only
      partially reversed at higher concentrations. Changes in the electrophysiological
      properties were not evident when the donor had been a priori depleted of NO. The
      results extend previous reports that NO induces reversible axonal conduction
      deficits. They provide new evidence of dissociation of the effects of NO on CAP
      and CMP during washout, and after prolonged exposure to the donor. They add
      support to the emerging concept that immune-mediated axonal conduction failure
      contributes to reversible neurologic deficits following neurotrauma and aid in
      understanding clinical phenomena such as spinal shock and neurologic recovery.

PMID- 17184189
TI  - beta-tubulin is a more suitable internal control than beta-actin in western blot
      analysis of spinal cord tissues after traumatic injury.
AB  - Western blot is a widely used method for determining specific protein levels. To
      control and correct for loading error, an internal control is often used. To
      date, two housekeeping geneacoded proteins (i.e., beta-actin and beta-tubulin)
      are widely used as internal controls in the Western blot analysis. However, no
      information is available concerning the stability of their expressions in
      response to a traumatic injury to the central nervous system (CNS). If so, their
      use as an internal control may have a negative impact on data acquisition,
      analysis, and interpretation. Using Western blot analysis, we demonstrated that
      spinal cord injury (SCI) induced a significant increase in beta-actin expression
      which peaked at 7 days post-SCI (2.48-fold). Coefficient of variation (CV)
      analysis showed that the CV of beta-actin expression was 43.79 +/- 4.67%,
      significantly higher than that of six loadings from a single sample (6.5 +/-
      0.9%, p < 0.01), indicating that increased expression of beta-actin was a result
      of SCI, instead of a loading error. In contrast, no statistically significant
      difference was found in beta- tubulin expression following SCI, compared with
      sham-operated controls. The CV of beta-tubulin expression following SCI was 14.3
      beta 3.96%, significantly less than that of the beta-actin expression (43.79 +/-
      4.67%; p < 0.01). Taken together, our study suggests that beta-actin whose
      expression increases following SCI is not a suitable internal control for Western
      blot analysis of spinal cord tissues following a traumatic injury. In contrast,
      beta-tubulin, whose expression was not significantly affected by SCI, is a better
      choice for the internal control.

PMID- 17184190
TI  - Lasting neuroendocrine-immune effects of traumatic brain injury in rats.
AB  - Traumatic brain injury (TBI) is a principal cause of long-term physical,
      cognitive, behavioral, and social deficits in young adults, which frequently
      coexist with a high incidence of substance abuse disorders. However, few studies
      have examined the long-term effects of TBI on the neuroendocrine-immune system.
      TBI was induced in adult male rats under isoflurane anesthesia by cortical
      contusion injury with a pneumatic piston positioned stereotaxically over the left
      parietal cortex. Controls underwent sham surgery without injury. At 4 weeks post
      injury, the plasma corticosterone response to 30-min restraint stress was
      significantly blunted in TBI rats compared to the sham controls. One week later,
      transmitters were implanted for continuous biotelemetric recording of body
      temperature and spontaneous locomotor activity. At 6 weeks post-injury, the
      febrile response to i.p. injection of the bacterial endotoxin, lipopolysaccharide
      (LPS; 50 microg/kg), was significantly lower in TBI than in sham rats. At 8
      weeks, swimming in the forced swim test was significantly less in TBI than sham
      rats. At 9 weeks, rats were rendered ethanol (EtOH) dependent by feeding an EtOH
      containing liquid diet for 14 days. Cosine rhythmometry analysis of circadian
      body temperature Midline Estimating Statistic of Rhythm (MESOR), amplitudes, and
      acrophases indicated differential effects of EtOH and withdrawal in the two
      groups. Light- and dark-phase activity analysis indicated that TBI rats were
      significantly more active than the sham group, and that EtOH and withdrawal
      differentially affected their activity. Given the extensive interactions of the
      neuroendocrine-immune systems, these results demonstrate that TBI produces
      lasting dysregulation amidst the central substrates for allostasis and circadian
      rhythmicity.

PMID- 17184191
TI  - Effects of estradiol on cognition and hippocampal pathology after lateral fluid
      percussion brain injury in female rats.
AB  - Studies involving animal models of acute central nervous system (CNS) stroke and
      trauma strongly indicate that sex and/or hormonal status are important
      determinants of outcome after brain injury. The present study was undertaken to
      examine the ability of estradiol to protect hippocampal neurons from lateral
      fluid percussion brain injury. Sprague-Dawley female rats (211-285 g; n = 119)
      were ovariectomized, and a subset (n = 66) were implanted with 17beta-estradiol
      pellets to provide near physiological levels of estradiol. Animals were subjected
      to lateral fluid percussion brain injury or sham injury 1 week later. Activation
      of caspase-3 (n = 26) and TUNEL staining (n = 21) were assessed at 3 and 12 h
      after injury, respectively, in surviving control and estradiol-treated animals.
      Memory retention was examined using a Morris water maze test in a separate subset
      of animals (n = 43) at 8 days after injury. Activated caspase-3 and TUNEL
      staining were observed in the dentate hilus, granule cell layer, and CA3 regions
      in all injured rats, indicative of selective hippocampal cell apoptosis in the
      acute posttraumatic period. Estradiol did not significantly alter the number of
      hippocampal neurons exhibiting caspase-3 activity or TUNEL staining. Brain injury
      impaired cognitive ability, assessed at 1 week post-injury (p < 0.001). However,
      estradiol at physiological levels did not significantly alter injury-induced loss
      of memory. These data indicate that estradiol at physiological levels does not
      ameliorate trauma-induced hippocampal injury or cognitive deficits in
      ovariectomized female rats.

PMID- 17184192
TI  - Penetrating ballistic-like brain injury in the rat: differential time courses of
      hemorrhage, cell death, inflammation, and remote degeneration.
AB  - Acute and delayed cerebral injury was assessed in a recently developed rat model
      of a penetrating ballistic-like brain injury (PBBI). A unilateral right frontal
      PBBI trajectory was used to induce survivable injuries to the frontal cortex and
      striatum. Three distinct phases of injury progression were observed. Phase I
      (primary injury, 0-6 h) began with immediate (<5 min) intracerebral hemorrhage
      (ICH) that reached maximal volumetric size at 6 h (27.0 +/- 2.9 mm(3)). During
      Phase II (secondary injury, 6-72 h), a core lesion of degenerate neurons
      surrounding the injury track expanded into peri-lesional areas to reach a maximal
      volume of 69.9 +/- 6.1 mm(3) at 24 h. The core lesion consisted of predominately
      necrotic cell death and included marked infiltration of both neutrophils (24 h)
      and macrophages (72 h). Phase III (delayed degeneration, 3-7 days) involved the
      degeneration of neurons and fiber tracts remote from the core lesion including
      the thalamus, internal capsule, external capsule, and cerebral peduncle. Overall,
      different time courses of hemorrhage, lesion evolution, and inflammation were
      consistent with complementary roles in injury development and repair, providing
      key information about these mediators of primary, secondary, and delayed brain
      injury development. The similarities/differences of PBBI to other focal brain
      injury models are discussed.

PMID- 17184193
TI  - Marked protection by selective cerebral profound hypothermia after complete
      cerebral ischemia in primates.
AB  - Hypothermia has been demonstrated to protect the brain from ischemia or traumatic
      brain injury. Achieving profound hypothermia has relied on techniques requiring
      total body cooling, which may result in serious cardiovascular and pulmonary
      complications. A technique to selectively cool the brain could conceivably exert
      a marked protection on cerebral structures and provide a relatively bloodless
      operative surgical field without systemic complications. Accordingly, this
      approach was tried in 7 rhesus monkeys after induction of general anesthesia. The
      right internal carotid artery and both internal jugular veins were each
      occlusively cannulated and connected to a circulation pump. The left internal
      carotid artery, both external carotid arteries, and both external jugular veins
      were temporarily clamped to establish severe cerebral ischemia. Using a closed
      circuit system, cooled Ringer's lactate liquid (4 degrees C) was infused through
      right internal carotid artery with outflow draining though both internal jugular
      veins. Cooled perfusate decreased cerebral temperature to the target temperature
      of 15 degrees C. Thereafter, pump flow was discontinued, and brains were rewarmed
      spontaneously, while the temporarily clamped carotid arteries and jugular veins
      were opened to resume normal cerebral blood circulation. Neurological functions
      were recorded daily and cerebral histology was examined at the conclusion of the
      experiment. Magnetic resonance (MR) scans were routinely taken before and 3 weeks
      after ischemia. In the normothermia control group of five rhesus monkeys,
      Ringer's solution at 37 degrees C was infused in the same manner as the cold
      solution with cerebral temperature maintained at 36.7 +/- 0.32 degrees C. Right
      cerebral temperature decreased from 36.5 +/- 0.49 to 15.5 +/- 2.29 degrees C, and
      simultaneously the left cerebral temperature decreased from 36.4 +/- 0.38 to 16.3
      +/- 2.4 degrees C for 62.8 +/- 9.76 min during selective cerebral cooled Ringer's
      liquid perfusion. In contrast, rectal temperature was only reduced to 32.4 +/-
      0.96 degrees C from a baseline of 37.2 +/- 0.76 degrees C. Internal jugular vein
      hematocrit was 38.2 +/- 0.31% before perfusion and 2.82 +/- 0.46% at the end of
      perfusion in profound hypothermia group; hematocrit was 39.7 +/- 0.62% before
      perfusion and 3.42 +/- 0.38% at the end of perfusion in the normothermia group.
      In the hypothermic group, neurological functions were normal during 6 months of
      follow-up, and microscopic examination of brain tissue did not show evidence of
      pathological changes in hippocampus or medulla. MR scans did not show any
      cerebral infarction. In contrast, none of the monkeys in normothermia group
      survived for more than several hours, and microscopic examination of the brain
      revealed extensive neuronal necrosis within the medulla. Selective cerebral
      profound hypothermia provides significant histologic and neurologic protection
      after severe cerebral ischemia. In addition, there were no major complications,
      and the operative field remained relatively bloodless in the profound hypothermic
      group.

PMID- 17184194
TI  - Proximity of lesioning determines response of facial motoneurons to peripheral
      axotomy.
AB  - We recently found that rubrospinal (RS) neurons, which typify central neurons
      projecting within the central nervous system (CNS), exhibited different neuronal
      and glial reactions to axotomy at proximal as opposed to distal sites. To
      determine whether distance also determines the reaction to axonal injury of
      central neurons projecting to the periphery, we studied the temporal expression
      of four free-radical-related enzymes as well as the severity of cell loss,
      perineuronal astrocytic and microglial reactions, and degeneration of the
      proximal central axons of facial motoneurons after axotomies performed at various
      sites on the brainstem surface and in the stylomastoid foramen, respectively.
      Distal lesions resulted in upregulation of these neurons' expression of nitric
      oxide synthase (NOS) and persistent downregulation of their expression of the NOS
      activating enzyme calcineurin. It also led to transient upregulation of their
      expression of manganese-dependent superoxide dismutase (Mn-SOD), and resulted in
      a mild neuronal loss. Proximal axotomy led to an upregulation of NOS but a
      transient downregulation in the expression of calcineurin and Mn-SOD at 4 weeks
      after injury. This was accompanied by severe cell loss and swelling of
      mitochondria at 2-4 weeks postinjury. However, neither proximal nor distal axonal
      lesioning led to nuclear fragmentation or TUNEL staining of neurons. Proximal as
      opposed to distal axotomy produced an earlier transformation of glial morphology,
      including the hypertrophy of astrocytic processes and metamorphosis of ramified
      microglia to amoeboid cells. We unexpectedly found that unlike RS neurons, whose
      central axons degenerated slowly and in an anterograde manner only after the
      severe cell loss induced by proximal axotomy, the central axons of facial
      motoneurons degenerated rapidly and in a retrograde manner independently of the
      severity of loss of these neurons after axotomy. However, degeneration began
      sooner after proximal than after distal axotomy. Since the central axons of both
      rubrospinal neurons and facial motoneurons lie within the CNS, the differences in
      whether and how they degenerated after axotomy suggests that central neurons that
      project within and outside the CNS are inherently different. The significance of
      these and also the free radical environment regulation differences between these
      two types of neurons following close and distant axotomies remains to be
      explored.

PMID- 17184195
TI  - Limited role of inducible nitric oxide synthase in blood-brain barrier function
      after experimental subarachnoid hemorrhage.
AB  - Excessive nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS)
      may play a pivotal role in blood-brain barrier (BBB) breakdown following
      subarachnoid hemorrhage (SAH). We investigated if the inhibition of iNOS could
      reduce BBB breakdown and cerebral edema, thereby leading to improved outcome 24 h
      after SAH. Forty male rats were assigned to three groups: control, SAH, and
      treatment groups. SAH was induced by perforating the bifurcation of the internal
      carotid artery. The neurological score and the mortality were evaluated 24 h
      after the surgery. The expression of iNOS, the concentration of NO metabolites,
      morphological changes in neuronal cells, water content, and IgG leakage were also
      evaluated. The expression of iNOS, as well as the concentration of NO
      metabolites, was elevated after SAH. Treatment with p-Toluenesulfonate decreased
      both the expression of iNOS and the concentration of NO metabolites. However,
      there was no significant change in water content, BBB disruption, or
      morphological findings between the SAH group and the treatment group. Furthermore
      no significant differences in neurological score or mortality were observed. The
      iNOS inhibitor failed to reduce BBB breakdown, brain edema, and neuronal cell
      death and failed to improve the neurological score and the mortality 24 h after
      SAH.

PMID- 17184196
TI  - Metabosensitive afferent fiber responses after peripheral nerve injury and
      transplantation of an acellular muscle graft in association with schwann cells.
AB  - Studies dedicated to the repair of peripheral nerve focused almost exclusively on
      motor or mechanosensitive fiber regeneration. Poor attention has been paid to the
      metabosensitive fibers from group III and IV (also called ergoreceptor).
      Previously, we demonstrated that the metabosensitive response from the tibialis
      anterior muscle was partially restored when the transected nerve was immediately
      sutured. In the present study, we assessed motor and metabosensitive responses of
      the regenerated axons in a rat model in which 1 cm segment of the peroneal nerve
      was removed and immediately replaced by an autologous nerve graft or an acellular
      muscle graft. Four groups of animals were included: control animals (C, no
      graft), transected animals grafted with either an autologous nerve graft (Gold
      Standard-GS) or an acellular muscle filled with Schwann Cells (MSC) or Culture
      Medium (MCM). We observed that (1) the tibialis anterior muscle was atrophied in
      GS, M(SC) and M(CM) groups, with no significant difference between grafted
      groups; (2) the contractile properties of the reinnervated muscles after nerve
      stimulation were similar in all groups; (3) the metabosensitive afferent
      responses to electrically induced fatigue was smaller in M(SC) and MCM groups;
      and (4) the metabosensitive afferent responses to two chemical agents (KCl and
      lactic acid) was decreased in GS, M(SC) and M(CM) groups. Altogether, these data
      indicate a motor axonal regeneration and an immature metabosensitive afferent
      fiber regrowth through acellular muscle grafts. Similarities between the two
      groups grafted with acellular muscles suggest that, in our conditions, implanted
      Schwann cells do not improve nerve regeneration. Future studies could include
      engineered conduits that mimic as closely as possible the internal organization
      of uninjured nerve.

PMID- 17184197
TI  - Stimulation of prostaglandin EP2 receptors prevents NMDA-induced excitotoxicity.
AB  - Prostaglandin E(2) (PGE(2)) plays an important role in inflammation and
      neurologic disorders. The neuromodulatory effects of PGE(2) are mediated through
      regulation of four G-protein-coupled receptors known as EP1, EP2, EP3, and EP4.
      The goal of the current study was to determine whether EP2 receptor activation
      protects neurons from acute NMDA-mediated excitotoxicity. To examine the effects
      of EP2 activation, mice were given an injection of the EP2 receptor-selective
      agonist butaprost (K (i) = 110 nM for EP2 receptor; K (i) > 10,000 for other
      prostaglandin receptors) in the cerebral ventricle and then an injection of NMDA
      in the right striatum. After 48 h, a significant reduction in NMDA-induced lesion
      volume was observed in groups pretreated with butaprost (1-300 nmol/L), with
      maximal protection at 100 nmol/L (p < 0.001). To determine if EP2-activated
      protection was specific to neurons, mouse neuronal cultures were treated with
      butaprost, and cell viability was analyzed after 24 h of NMDA excitotoxicity. The
      results showed that butaprost significantly increased neuron survival in a dose
      dependent fashion. Furthermore, treatment of primary neurons with butaprost
      significantly increased cAMP levels (p < 0.001). Together, these data reveal that
      EP2 receptor stimulation mediates neuroprotection against NMDA excitotoxicity
      both in vivo and in vitro and that butaprost can limit acute brain damage.
      Development and testing of specific PGE(2) receptor mimetics could lead to a
      decrease in side effects associated with anti-inflammatory drugs and could help
      to fight acute and/or chronic neurologic disorders.

PMID- 17184198
TI  - Plasma proteins in edematous white matter after intracerebral hemorrhage confound
      immunoblots: an ELISA to quantify contamination.
AB  - Intracerebral hemorrhage (ICH) and traumatic brain injury can induce brain tissue
      edema (i.e., interstitial and/or vasogenic), containing high concentrations of
      plasma proteins. To understand biochemical processes in edema development
      following these insults, it would be useful to examine alterations in various
      proteins (e.g., transcription factors, signaling). However, determining altered
      protein responses in edematous brain tissue using standard immunoblotting
      techniques is problematic due to contaminating plasma proteins. To solve this
      problem, we developed an enzyme-linked immunosorbent assay (ELISA) method to
      quantify the two major plasma proteins, albumin and immunoglobulin G (IgG), that
      comprise about 80% of the total plasma proteins. We tested our method on
      edematous white matter samples from our porcine ICH model. To induce ICH, we
      infused autologous arterial whole blood (3 mL) into frontal hemispheric white
      matter of pentobarbital- anesthetized pigs ( approximately 20 kg) over 15 min. We
      froze brains in situ at various times up to 24 h post- ICH and sampled white
      matter adjacent and contralateral to hematomas. We prepared cytoplasmic extracts
      that we subjected to ELISA and immunoblotting analyses. Our results demonstrate
      that this ELISA method is accurate, reproducible, and enables the concentrations
      of albumin and IgG in edematous brain tissue samples to be accurately determined.
      By using this correction method, equal amounts of cellular protein can be loaded
      onto gels during immunoblotting procedures. This method is applicable to
      edematous tissue samples in brain injury models in which high plasma protein
      concentrations result from interstitial or vasogenic edema development.

PMID- 17184199
TI  - Can pharmacogenetics help smokers quit?

PMID- 17184200
TI  - Could gene therapy prevent the effects of irradiation exposure?

PMID- 17184202
TI  - Microarrays Technologies 2006: an overview.

PMID- 17184203
TI  - DOPA decarboxylase gene is associated with nicotine dependence.
AB  - INTRODUCTION: Cigarette smoking is a prevalent and harmful behavior. Although the
      heritability of nicotine dependence (ND) is well documented and many candidate
      genetic regions have been identified, few of them were confirmed. This may be, in
      part, due to analytic methods that sacrifice power. METHODS: Using a recently
      developed, more powerful method for testing association between a genetic marker
      and an ordinal trait, we analyzed data from 1879 smokers and nonsmokers from 600
      nuclear families of African- or European-American (AA or EA) ancestry. This
      method increases power principally by accounting for differences in severity
      between affected subjects. RESULTS: To demonstrate the more powerful method, we
      re-analyzed an existing dataset, which confirmed the association of the DOPA
      decarboxylase (DDC) gene on chromosome 7p11 with measures of nicotine dependence.
      Although none of the eight single nucleotide polymorphisms (SNPs) studied were
      found to be significantly associated with nicotine dependence (unadjusted p-value
      > 0.01), we identified haplotypes from those SNPs that were significantly
      associated with nicotine dependence in both AA and EA samples. CONCLUSION: The
      associated haplotypes differed in the AA and EA samples. The strongest
      association (p-value = 0.003) was identified between the 'heaviness of smoking
      index' and haplotype C-A-T-G in SNPs rs921451-rs3735273-rs1451371-rs2060762.
      However, this association was not found significant in a previous report (p-value
      = 0.19) that used the same sample, underscoring the importance of using the
      statistical methods that use more of the available phenotypic information, and
      thereby better reflect the distribution of the phenotypes.

PMID- 17184204
TI  - Gene-expression signatures in oncology diagnostics.
AB  - The advent of DNA microarray technologies has enabled the development of gene
      expression signatures that can be used for prognostic and predictive purposes.
      This new information can change the paradigm of how medicine is practiced,
      coupling physical examination, pathology and clinical tests with new molecular
      information. However, many unanswered questions regarding sample acquisition,
      platform development, signature validation and clinical trial design will need to
      be addressed before this new medical content will have an impact on the clinical
      setting. This article will examine some of these issues in greater detail,
      focusing on tissue type, platform comparison, biospecimen collection and
      signature validation.

PMID- 17184205
TI  - Overview of the pharmacoeconomics of pharmacogenetics.
AB  - Pharmacoeconomics and pharmacogenetics are two fields converging together as it
      is increasingly recognized that genetic markers predicting efficacy and toxicity
      to drugs can cost-effectively improve patient care. While pharmacogenetics aims
      at identifying genetic markers underlying the response to drugs,
      pharmacoeconomics aims at delivering healthcare cost-effectively. Several studies
      have investigated the potential cost-effectiveness of pharmacogenetic-based
      approaches. Recent evidences include screening for thiopurine methyltransferase
      gene polymorphisms to prevent azathioprine-induced myelosuppression, or screening
      for human leukocyte antigen (HLA)B5701 to prevent hypersensitivity reactions to
      abacavir therapy. Furthermore, examples suggesting a cost-effectiveness of
      markers predicting drug efficacy include screening the angiotensin-converting
      enzyme gene polymorphisms for statins therapy, the alpha-adducin gene variant for
      diuretic therapy and the assessment of human epidermal growth factor receptor
      (HER2) expression for trastuzumab therapy. However, thus far, all these
      pharmacoeconomic analyses are exploratory and validations in prospective
      randomized clinical trials are warranted.

PMID- 17184206
TI  - Gene therapy of fibroproliferative vasculopathies: current ideas in molecular
      mechanisms and biomedical technology.
AB  - Intimal hyperplasia occurs primarily as a part of the pathogenesis of coronary
      artery disease or secondary to therapeutic intervention in relieving vascular
      occlusion. Intimal hyperplasia involving vascular smooth muscle cells is found in
      atherosclerosis, post-balloon angioplasty restenosis, in-stent restenosis and
      vein graft disease, predominantly involving the use of saphenous vein conduits in
      coronary artery bypass grafting procedures. One potentially exciting area is that
      of gene therapy. Gene and protein expression patterns at the site of
      vasculoproliferative lesions have been widely studied and several target areas
      have been identified on the basis of whether the gene has an antiproliferative,
      proapoptotic, matrix degrading or endothelial protective action. Blood vessels
      are easily accessible for the delivery of the gene product, and experimental
      studies using animal models have used catheter-delivered gene products at the
      site of vascular injury. Currently, the application of antisense technology and
      adenoviral vector-mediated delivery has shown significant promise, albeit in in
      vitro or animal model settings. In this review, we discuss the current knowledge
      in the application of gene therapy in fibroproliferative vasculopathies. We
      examine some of the cellular mechanisms and intermediaries which could be
      potential candidates for gene targeting. We also present some of the advances in
      biomedical technology that might provide useful vehicles for pinpoint delivery of
      the gene product. Could the future of restenosis treatment be in gene therapy or
      is it misplaced enthusiasm?

PMID- 17184207
TI  - Could endogenous substrates of drug-metabolizing enzymes influence constitutive
      physiology and drug target responsiveness?
AB  - Integration of genomic data from pharmacokinetic pathways and drug targets is an
      emerging trend in bioinformatics, but is there a clear separation of
      pharmacokinetic pathways and drug targets? Should we also consider the potential
      interactions of endogenous substrates of drug-metabolizing enzymes with receptors
      and other molecular drug targets as we combine pharmacogenomic datasets? We
      discuss these overarching questions through a specific pharmacogenomic case study
      of the cytochrome P450 (CYP)2D6, serotonin and dopamine triad. Importantly,
      CYP2D6 may contribute to the regeneration of serotonin from 5-methoxytryptamine
      by virtue of its catalytic function as a 5-methoxyindolethylamine O-demethylase.
      Furthermore, serotonergic neurons provide a regulatory feedback on dopaminergic
      neurotransmission. Hence, we hypothesize that independent of its role as a
      pharmacokinetic gene, CYP2D6 may nuance the regulation of serotonergic and
      dopaminergic neurophysiology. Additionally, we reflect upon the contribution of
      hyperspecialization in biomedicine to the present disconnect between research on
      pharmacokinetics and drug targets, and the potential for remedying this important
      gap through informed dialogue among clinical pharmacologists, human geneticists,
      bioethicists and applied social scientists.

PMID- 17184208
TI  - Pharmacogenetics of irinotecan: clinical perspectives on the utility of
      genotyping.
AB  - Depending upon the UDP glucuronosyltransferase 1A1 (UGT1A1) genotype, patients
      are more or less susceptible to the risk of severe toxicity of irinotecan. As the
      US FDA-approved label of irinotecan (CPT-11, Camptosar) has been recently revised
      to include UGT1A1 genotype among potential risk factors for toxicity, it is
      expected that UGT1A1 genotyping will be increasingly used in patients undergoing
      irinotecan treatment. At present, the label states that *28/*28 (7/7) genotype
      patients are at higher risk of neutropenia and should be treated at a lower dose
      of irinotecan. Although effective alternative drugs (i.e., oxaliplatin) exist for
      metastatic colorectal cancer (the main indication of irinotecan), recent studies
      have confirmed that irinotecan has an important place in the management of this
      disease. We feel that now is the time for addressing questions around the
      UGT1A1*28 testing that many oncologists might have had but remained unanswered.
      For example, does the test have adequate sensitivity/specificity? Can the test
      results be effectively utilized to guide therapy of metastatic colorectal cancer
      patients? Is it possible that the *1/*1 (6/6) patients are underdosed? How can
      the genetic prediction of irinotecan toxicity be improved? Is the UGT1A1*28 test
      fully predictive of the UGT1A1 deficiency in patients who are not of Caucasian
      origin? Clinicians and investigators interested in a discussion of each of these
      points could find this article a useful source.

PMID- 17184209
TI  - Search for shortcuts on the critical path to market: US FDA perspectives from the
      diagnostic side.
AB  - The US FDA has been regulating medical devices (including laboratory tests) since
      1976. Premarket review is well defined and may include requirements for both
      analytical and clinical information. In 2004, the US FDA initiated the Critical
      Path initiative to help foster development of new medical products. Biomarkers
      were seen as an important part of this new program for both traditional
      diagnostic purposes and to aid in drug development. The US FDA has created
      programs to foster use of biomarkers both for routine diagnostic and for drug
      development purposes. There is growing methodology to serve as road maps for
      efficient and scientifically sound development in this area. The US FDA has a
      flexible regulatory tool box to apply to biomarker development, and has the clear
      aim of working as a partner to bring these important medical devices quickly to
      the medical marketplace.

PMID- 17184210
TI  - Combination vaccines: design strategies and future trends.

PMID- 17184213
TI  - Present and future cholera vaccines.

PMID- 17184214
TI  - Modern Vaccine Adjuvants and Delivery Systems--second International Conference.

PMID- 17184215
TI  - Marek's disease virus: lytic replication, oncogenesis and control.
AB  - Marek's disease (MD) is caused by a ubiquitous, lymphotropic alphaherpesvirus, MD
      virus (MDV). MD has been a major concern in the poultry industry owing to the
      emergence of increasingly virulent strains over the last few decades that were
      isolated in the face of comprehensive vaccination. The disease is characterized
      by a variety of clinical signs; among them are neurological symptoms, chronic
      wasting and, most notably, the development of multiple lymphomas that manifest as
      solid tumors in the viscera and musculature. Much work has been devoted to study
      MD-induced oncogenesis and the genes involved in this process. Among the many
      genes encoded by MDV, a number have been shown recently to affect the development
      of tumors in chickens, one protein directly causing transformation of cells (Meq)
      and another being involved in maintaining transformed cells (vTR). Other MDV gene
      products modulate and are involved in early lytic in vivo replication, thereby
      increasing the chance of transformation occurring. In this review, we will
      summarize specific genes encoded by MDV that are involved in the initiation
      and/or maintenance of transformation and will focus mostly on current vaccination
      and control strategies against MD, particularly how modern molecular biological
      methods may be used to improve strategies to combat the disease in the future.

PMID- 17184216
TI  - Cancer vaccines and tumor dormancy: a long-term struggle between host antitumor
      immunity and persistent cancer cells?
AB  - Tumor dormancy is a phenomenon characterized by the persistence of residual
      cancer cells for long periods in the host. Evidence has emerged that a balance
      exists between the immune response and dormant tumor cells. This review presents
      our current understanding of the immune relationship between host and dormant
      tumor cells and the mechanism developed by these cells to escape host antitumor
      immunity. Implications of this immune escape for cancer vaccine strategy are
      considered.

PMID- 17184217
TI  - Human papillomavirus vaccines for the treatment of cervical cancer.
AB  - Human papillomavirus (HPV) infection is a major cause of cervical cancer, the
      second most common cancer in women worldwide. Currently, a HPV L1-based virus
      like particle has been approved as a prophylactic vaccine against HPV infection,
      which will probably lead to a reduction in cervical cancer incidence within a few
      decades. Therapeutic vaccines, however, are expected to have an impact on
      cervical cancer or its precursor lesions, by taking advantage of the fact that
      the regulatory proteins (E6 and E7) of HPV are expressed constantly in HPV
      associated cervical cancer cells. Vaccine types targeting these regulatory
      proteins include the recombinant protein and DNA vaccines, peptide vaccines,
      dendritic-cell vaccines, and viral and bacterial vector deliveries of vaccines,
      and these may provide an opportunity to control cervical cancer. Further
      approaches incorporating these vaccine types with either conventional therapy
      modalities or the modulation of CD4(+) regulatory T cells appear to be more
      promising in achieving increased therapeutic efficacy. In this review, we
      summarize current and future therapeutic vaccine strategies against HPV
      associated malignancies at the animal and clinical levels.

PMID- 17184218
TI  - Glioma-specific antigens for immune tumor therapy.
AB  - This review describes glioma-specific antigens important in immunotherapy of
      glioma tumors. The structure and function of these antigens and recent
      immunotherapy data are summarized. Also, some important aspects of tumor
      formation are outlined. The roles of neuronal precursor cells and tumor stroma
      cells are discussed. The stroma cells of the tumor may be of interest as a target
      for tumor therapy, especially since they are less heterogeneous than the tumor
      cells. To date, the clinical benefit of immunotherapy has been very limited.
      Immunotherapy is, however, still an extremely promising approach to tumor therapy
      and it will most likely be implemented as a future treatment option for many
      types of tumors. The current shortcomings of immunotherapy will probably diminish
      as we start to understand and are able to modulate tumor-induced
      immunosuppression. There is also a need for a continued search for new tumor
      specific antigens and to optimize protocols for vaccine administration.

PMID- 17184219
TI  - Optimization and delivery of plasmid DNA for vaccination.
AB  - Vaccination with DNA is one of the most promising novel immunization techniques
      against a variety of pathogens and tumors, for which conventional vaccination
      regimens have failed. DNA vaccines are able to stimulate both arms of the immune
      system simultaneously, without carrying the safety risks associated with live
      vaccines, therefore representing not only an alternative to conventional vaccines
      but also significant progress in the prevention and treatment of fatal diseases
      and infections. However, translation of the excellent results achieved in small
      animals to similar success in primates or large animals has so far proved to be a
      major hurdle. Moreover, biosafety issues, such as the removal of antibiotic
      resistance genes present in plasmid DNA used for vaccination, remain to be
      addressed adequately. This review describes strategies to improve the design and
      production of conventional plasmid DNA, including an overview of safety and
      regulatory issues. It further focuses on novel systems for the optimization of
      plasmid DNA and the development of diverse plasmid DNA delivery systems for
      vaccination purposes.

PMID- 17184220
TI  - Progress towards an HIV vaccine based on recombinant bacillus Calmette-Guerin:
      failures and challenges.
AB  - The need for an affordable, safe and effective HIV vaccine has never been
      greater. As the immunogenicity of all the vaccine vectors being evaluated
      currently in human populations is limited, novel vaccine strategies are needed to
      stimulate the innate immune system, to generate high levels of neutralizing
      antibodies and to induce strong cell-mediated and mucosal immunity. There is
      strong evidence for a role for cytotoxic T lymphocytes in the containment of HIV
      replication. Several vaccine approaches have been tested to elicit anti-HIV
      cytotoxic T-lymphocyte responses. One promising approach is Bacillus Calmette
      Guerin (BCG) as a bacterial live recombinant vaccine vehicle. BCG has a long
      record of safety in humans and is able to induce long-lasting immunity. In this
      review, we describe the limitations and challenges of developing a recombinant
      BCG-based HIV vaccine. We also emphasize possible approaches for overcoming the
      plasmid instability in vivo and the low levels of gene expression and
      immunogenicity induction. Today, projects all over the world are focused on the
      development of an AIDS vaccine. Overcoming the remaining scientific, logistical
      and financial hurdles to the development of an effective HIV vaccine will require
      real imagination and firm commitment from all stakeholders.

PMID- 17184221
TI  - Chloroplast-derived anthrax and other vaccine antigens: their immunogenic and
      immunoprotective properties.
AB  - Transgenic plants offer many advantages, including low cost of production (by
      elimination of fermenters), storage and transportation, heat stability, absence
      of human pathogens, protection of antigens in the stomach through
      bioencapsulation (when delivered orally), elimination of the need for expensive
      purification and sterile injections and generation of both systemic and mucosal
      immunity. Recent studies have demonstrated that chloroplast-derived anthrax
      protective antigen elicits effective immune responses, develops neutralizing
      antibodies, confers complete protection against anthrax lethal toxin challenge
      and produces 360 million doses of vaccine in one acre of transgenic plants.
      Chloroplast-derived vaccine antigens are efficacious against bacterial, fungal,
      viral and protozoan pathogens.

PMID- 17184222
TI  - Long-term protection in children with meningococcal C conjugate vaccination:
      lessons learned.
AB  - Owing to an increase in group C disease, extensive prelicensure studies have been
      funded by both the UK Department of Health and vaccine manufacturers. These
      demonstrated the safety and immunogenicity of three candidate meningococcal group
      C conjugate (MCC) vaccines (two conjugated to CRM(197) and one to tetanus toxoid)
      in the targeted age groups. Induction of immunological memory in infants and
      young children was also demonstrated by either a low dose of polysaccharide
      challenge following primary immunization with MCC or by an increase in avidity
      indices post-primary to pre-challenge. Immune memory after infant immunization
      persisted to at least 4 years of age, although antibody persistence in this age
      group was poor. MCC vaccine was introduced into the UK routine immunization
      schedule at 2, 3 and 4 months of age in 1999, with a catch-up as a single dose to
      all children aged 1-18 years with two doses for infants aged 5-11 months. The
      number of group C cases fell rapidly in the targeted age groups and early
      analyzes showed high vaccine effectiveness in all age groups together with
      significant herd immunity. However, when effectiveness was measured again more
      than 1 year after vaccination, there was a significant decline in all age groups,
      most marked in infants vaccinated in the routine infant immunization program, for
      whom there was no demonstrable efficacy after only 1 year and then in toddlers
      for whom efficacy declined to 61% (95% confidence interval: -327-94) from 88%
      (95% confidence interval: 65-96) in the first year. However, good disease control
      was maintained in the UK with only low numbers of vaccine failures. The
      assumption that immune memory was predictive of long-term protection is
      incorrect, at least after vaccination in infancy. Persistence of antibody and
      herd immunity may be more relevant for long-term disease control.

PMID- 17184223
TI  - Opportunistic fungi and fungal infections: the challenge of a single, general
      antifungal vaccine.
AB  - A vaccine made up by an algal beta-glucan (laminarin), conjugated with a protein
      component, protects against infections by different fungi and induces antibodies
      capable of inhibiting fungal growth. Although taking a premium on a common
      molecular theme, this remains a sort of 'cross-kingdom' vaccine because the
      immunizing antigen and the vaccination target belong to organisms from two
      different kingdoms and this is certainly the first case in the field of human
      vaccines. Thus, it is possible to convey in a single immunological tool the
      potential to protect against multiple infections, in theory all those caused by
      beta-glucan-expressing fungi. The generation of antibodies with the potential to
      directly inhibit the growth of, or kill the fungal cells also opens an exciting
      perspective for both active and passive vaccination in immunocompromised
      subjects.

PMID- 17184224
TI  - Chlorhexidine varnish for preventing dental caries in children, adolescents and
      young adults: a systematic review.
AB  - This systematic review aimed to determine the caries-inhibiting effect of
      chlorhexidine (CHX) varnishes on the permanent dentition of children, adolescents
      and young adults, and to explore two possibly related factors, namely application
      frequency and the time between evaluation and the last application. The
      literature search identified 14 publications of randomized controlled trials or
      controlled clinical trials where the effect of CHX varnish was compared with
      placebo controls or controls that received no preventive treatment. To obtain
      uniform outcome effects, the prevented fraction and 95% confidence intervals of
      caries increment were calculated. Owing to insufficient data presentation, only
      eight publications were included. Another two publications were included after
      receiving additional data from the authors. This systematic review did not result
      in a meta-analysis as an overall prevented fraction could not be computed because
      of the large variation of outcome results. The variation could not be explained
      by the time between evaluation and last application but might be explained by
      application frequency. It is tentatively concluded that CHX varnish has a
      moderate caries-inhibiting effect when applied every 3-4 months. However, this
      effect seems to have diminished by around 2 yr after the last application. There
      is no evidence for a caries-inhibiting effect of CHX varnish with longer
      intervals between applications.

PMID- 17184225
TI  - Taste deficits related to dental deafferentation: an electrogustometric study in
      humans.
AB  - Dental treatments, the prevalence of which increases with age, can cause
      orofacial somatosensory deficits. In order to examine whether they may also
      affect taste sensitivity, electrogustometric thresholds were measured at 9 loci
      on the tongue surface in 391 healthy non-smoking, non-medicated subjects. Results
      showed that the greater the number of deafferented teeth, the higher the
      thresholds. Irrespective of age, subjects with more than 7 deafferented teeth
      exhibited significantly higher thresholds than subjects with fewer than 7
      deafferented teeth. Conversely, across age groups, no statistical difference was
      observed among subjects with no, or few, deafferented teeth. Hence, a taste
      deficit, which was not correlated to aging, was observed. An association was
      noticed between the location of taste deficits and the location of deafferented
      teeth. Higher thresholds at anterior sites, with no possible traumatic injury
      relationship, suggested that neurophysiological convergence between dental
      somatosensory and taste pathways - possibly in the nucleus tractus solitarius -
      could be responsible for these relative decreases of taste sensitivity when
      dental afferences were lacking. Among trigeminal contributions, lingual nerve and
      inferior alveolar nerve may synergize taste.

PMID- 17184226
TI  - Mandibular jaw movement capacity in 10-17-yr-old children and adolescents:
      normative values and the influence of gender, age, and temporomandibular
      disorders.
AB  - The aims of this study were, first, to report normative values for jaw movements
      in Caucasian children and adolescents (maximum opening, laterotrusion, and
      protrusion) and, second, to investigate the influence of age, gender, and
      temporomandibular disorders (TMD) on jaw movement capacity. The population-based
      study included 1,011 randomly selected German children and adolescents, aged 10
      17 yr. Case histories, as well as mandibular movements and the presence of TMD,
      were assessed according to the Research Diagnostic Criteria for Temporomandibular
      Disorders (RDC/TMD). The mean +/- standard deviation for maximum opening was 50.6
      +/- 6.4 mm, for laterotrusion to the right was 10.2 +/- 2.2 mm, for laterotrusion
      to the left was 10.6 +/- 2.3 mm, and for protrusion was 8.2 +/- 2.5 mm.
      Bivariable (t-test) and multivariable (linear regression) analyses showed that
      normative values for jaw opening capacity were influenced by age and gender. No
      influence on jaw movement capacity was seen when TMD were present. Based on the
      distribution of the measurements in the population (lowest decentile), the
      mandibular mobility of subjects with a maximum opening of < 43 mm and
      laterotrusive movements < 8 mm or protrusive movements < 5 mm might be considered
      as being limited. However, these limitations do not necessarily require
      treatment.

PMID- 17184227
TI  - Mothers' perceptions of children's refusal to undergo dental treatment: an
      exploratory qualitative study.
AB  - Very little is known about mothers' beliefs concerning children's refusal of
      dental treatment. This qualitative study aimed to explore mothers' perceptions of
      their children's refusal to submit to dental treatment. Semistructured interviews
      were conducted with 14 mothers of 4-12-yr-old children resistant to dental
      treatment who were attending two pediatric dentists. Thematic content analysis
      was used to interpret the data. From this, three categories were developed and
      labeled origins of child behavior, caregiver attitudes, and the culture of
      resistance. The origins of the children's behavior were related to the childs'
      temperament, behavior disorders, lack of affection, level of development, and
      refusal to submit to health procedures or other situations. Caregiver's attitudes
      included discipline, protection, incoherence, partnership in dental treatment,
      and mother-child feeling. The culture of resistance referred to the parents' or
      guardians' refusal of dental treatment and the mothers' recognition of this. In
      conclusion, the wide variety of mothers' accounts reinforced the idea that every
      child is unique, and it is not possible to standardize child behavior models in a
      dental setting.

PMID- 17184228
TI  - Influence of the condition of the adjacent tooth surface on fluorescence
      measurements for the detection of approximal caries.
AB  - The aim of this study was to test whether the status of the adjacent tooth
      surface has an influence on the signal of a new laser fluorescence (LF) device
      for the detection of approximal caries. Seventy-eight teeth were selected from a
      pool of extracted permanent human molars, frozen at -20 degrees C until use.
      Before being measured the teeth were defrosted, cleaned, and any calculus
      removed. As a control, a defined approximal surface of each tooth was measured
      with the LF device holding the tip with the detecting- and the reverse-side on
      it, but without a neighboring tooth contacting the surface. The proximal site
      under examination was then placed adjacent to a tooth, which had deep dentinal
      caries, a composite restoration, a provisional ZnO-Eugenol restoration, or a
      ceramic restoration. The adjacent tooth with the ZnO-Eugenol restoration, the
      composite restoration, and the dentinal caries all demonstrated a statistically
      significant increase of LF readings on sound tooth surfaces. Teeth with enamel or
      dentinal caries were only slightly (and not statistically significantly)
      influenced by the different types of neighboring surfaces compared with the
      control LF readings. It can be concluded that caries detection of approximal
      tooth surfaces with the new LF system might be influenced by the condition of the
      adjacent tooth surface.

PMID- 17184229
TI  - Establishing quantitative light-induced fluorescence cut-offs for the detection
      of occlusal dentine lesions.
AB  - The aims of this in vitro study were, first, to define suitable cut-off values
      for the detection of occlusal dentine lesions by means of quantitative light
      induced fluorescence (QLF), and, second, to compare the validity of light
      microscopy (LM) and microradiography (MR) as reference standards. Fifty-four
      third molar occlusal fissures with sound sites or non-cavitated lesions were
      examined. Standard QLF equipment was used to capture, display, store, and analyze
      fluorescence images. Each tooth was cut into sections in the bucco-lingual
      direction using a microtome saw, and the caries levels were subsequently assessed
      with the two reference methods. The histological examination with LM indicated
      that 46% of the specimens had carious lesions progressing into the dentine
      compared with 41% measured using MR (D3-4 level). Using optimal cut-off levels
      for the detection of dentine lesions, the sensitivity and specificity values were
      > 80%. The area under the receiver operating characteristic curve was slightly
      higher for MR (0.91-0.93) than for LM (0.88-0.89). The results of this study give
      a good idea of suitable cut-off points for the detection of occlusal dentine
      lesions using QLF. Owing to the small number of specimens in this study, further
      studies should be carried out before establishing definite cut-offs.

PMID- 17184230
TI  - Fluoride concentrations in dental plaque and saliva after the use of a fluoride
      dentifrice preceded by a calcium lactate rinse.
AB  - Plaque fluoride concentrations ([F]) are directly related to plaque calcium
      concentrations [Ca]. Attempts to increase plaque F uptake from dentifrices or
      rinses have used methods designed to increase plaque [Ca] but with inconsistent
      results. This double-blind, double-crossover study tested the effect of a 150 mM
      calcium lactate rinse used prior to brushing with placebo or fluoridated
      dentifrices (1030 p.p.m. as NaF) on plaque and salivary [F] and [Ca]. Sixteen
      children (8-10 yr of age) were randomly assigned to four different groups
      according to the four treatments (placebo dentifrice or fluoridated dentifrice
      preceded by calcium lactate or deionized water prerinses). Plaque and saliva were
      collected 1 and 12 h after brushing on day 7 after starting to use the
      dentifrices. F was determined using the electrode and Ca was determined using
      atomic absorption spectrometry. Plaque and salivary [Ca] were not significantly
      increased after use of the calcium lactate prerinse, except for plaque [Ca] 1 h
      after the use of the placebo dentifrice. A significant increase in salivary [F]
      was associated with the calcium lactate prerinse only at 1 h after the use of the
      fluoridated dentifrice. The the calcium lactate prerinse did not significantly
      affect plaque [F] under any condition.

PMID- 17184231
TI  - Minor salivary gland secretion rates and immunoglobulin A in adults and the
      elderly.
AB  - Previously published data are conflicting about the effect of various factors on
      secretions from minor salivary glands. The aim of the present study was to
      investigate the secretion rate from palatal, buccal, and labial glands, and to
      analyze the immunoglobulin A (IgA) concentrations in relation to age, gender,
      circulatory disease, diabetes, medication, smoking, and pregnancy. Resting and
      stimulated whole-saliva secretion rates, as well as IgA concentration in
      stimulated whole saliva, were also examined. One-hundred and forty two
      individuals (96 women and 46 men), 18-82 yr of age, participated. The results did
      not suggest any effect of aging on the secretion capacity of minor salivary
      glands, but the IgA concentration seemed to increase with age. Women had lower
      buccal and labial saliva secretion rates, and lower levels of IgA in buccal
      saliva, than men. For whole saliva, resting, but not stimulated, saliva secretion
      rates were reduced with age, and the secretion rate of stimulated whole saliva
      was lower in women than in men. The IgA concentration in buccal saliva showed a
      positive correlation with IgA in stimulated whole saliva, and the IgA
      concentration decreased with increased flow rate in both salivas.

PMID- 17184232
TI  - Plasminogen activators and inhibitor type-1 in alveolar osteitis.
AB  - Alveolar osteitis (AO) is characterized by excess fibrinolysis, leading to early
      dissociation of the clot that normally follows tooth extraction. Nonetheless,
      scarce information is available on the fibrinolytic system in AO. In this study,
      we report on the differential composition of postextraction wound healing tissue
      and of peri-alveolar gingival epithelium from normal healing and AO patients in
      terms of plasminogen activators, plasminogen activator inhibitor-type 1, and
      urokinase-type plasminogen activator receptor. Plasminogen activators were
      studied by overlay zymography, western blotting, and enzyme-linked immunosorbent
      assay (ELISA). Plasminogen activator inhibitor-type 1 and urokinase receptor were
      measured by ELISA. In AO, the fibrinolytic activity of wound healing tissue was
      accounted for by an increase ( approximately 85%) of urokinase-type plasminogen
      activator, whereas tissue-type plasminogen activator was unchanged. Plasminogen
      activator inhibitor-type 1 showed a 6.7-fold increase in AO. These results point
      to key roles of urokinase in AO hyper-fibrinolysis and of plasminogen activator
      inhibitor type-1 in slowing down the healing response. Peri-alveolar gingival
      epithelium in AO showed an overall decrease of all the components of the
      fibrinolytic system, including the urokinase receptor, which indicates a decrease
      of the migration properties of epithelial cells.

PMID- 17184233
TI  - Ameloblastin expression during craniofacial bone formation in rats.
AB  - Based on previous results showing the expression of ameloblastin (Ambn; amelin)
      in the formation of mesenchymal dental hard tissues, we investigated its presence
      during bone development. Immunohistochemistry (IHC), in situ hybridization (ISH),
      and reverse transcription-polymerase chain reaction (RT-PCR) were used to
      investigate the expression of ameloblastin protein and mRNA during craniofacial
      development in rats. Tissue samples were collected on embryonic day 18 and from
      days 2-28 postnatally. IHC revealed the expression of ameloblastin during bone
      formation at embryonic and early postnatal stages with different patterns of
      expression in intramembranous and endochondral ossification. In intramembranous
      ossification, ameloblastin expression was detected in the superficial layer of
      the condensed vascularized primitive connective tissue and in the cellular layer
      covering the surface of the newly formed woven bone. In endochondral
      ossification, ameloblastin was expressed within the extracellular matrix of the
      cartilage templates and in the perichondrium. Between days 2 and 28 the
      expression decreased markedly, concordant with the maturation of the bone, and
      disappeared after completion of bone remodeling. The results obtained by IHC were
      confirmed by ISH and RT-PCR, showing the expression of ameloblastin mRNA during
      craniofacial bone formation. This study indicates the expression of the putative
      dental protein ameloblastin during craniofacial bone development in rats.

PMID- 17184234
TI  - Regional differences of expression of bone morphogenetic protein-2 and RANKL in
      the rat dental follicle.
AB  - Tooth eruption requires alveolar bone resorption and bone formation. The coronal
      half of the dental follicle probably mediates the bone resorption seen in the
      coronal region of the alveolar bony crypt, and the basal half of the follicle
      mediates bone growth in the basal region. We hypothesized that the expression of
      a gene for bone resorption--receptor activator of nuclear factor kappa B ligand
      (RANKL)--would be higher in the coronal than in the basal region of the follicle.
      Conversely, the level of expression of bone morphogenetic protein-2 (BMP-2), a
      gene for bone formation, would be higher in the basal region. Results obtained
      using laser-capture microdissection and real-time reverse transcription
      polymerase chain reaction (RT-PCR) confirmed the hypothesis. Scanning electron
      micrographs of the bony crypt showed that the coronal area of the crypt was
      scalloped in appearance (bone resorption), whereas the basal area was trabecular
      (bone formation). Thus, the differences in bone activity at opposite poles of the
      crypt appear to be caused by differences in the regional expression of genes in
      the dental follicle and suggest a molecular mechanism whereby the dental follicle
      could regulate both the alveolar bone resorption and formation needed for
      eruption.

PMID- 17184235
TI  - Expression of Pit2 sodium-phosphate cotransporter during murine odontogenesis is
      developmentally regulated.
AB  - Different sodium-dependent inorganic phosphate (P(i)) uptake mechanisms play a
      major role in cellular P(i) homeostasis. The function and detailed distribution
      patterns of the type III Na(+)-phosphate cotransporter, PiT-2, in different
      organs during development are still largely unknown. We therefore examined the
      temporospatial expression patterns of Pit2 during murine odontogenesis.
      Odontoblasts were always devoid of Pit2 expression, whereas a transient, but
      strong, expression was detected in young secretory ameloblasts. However, the
      stratum intermedium and, later on, the papillary layer and cells of the
      subodontoblastic layer, exhibited high levels of Pit2 mRNA, which increased
      gradually as the tooth matured. Hormonal treatment or P(i) starvation of tooth
      germs in vitro did not alter Pit2 levels or patterns of expression, indicating
      mechanisms of regulation different from those of PiT-1 or other cell types. PiT-2
      also functions as a retroviral receptor, and functional membrane-localized
      protein was confirmed throughout the dental papilla/pulp by demonstrating
      cellular permissiveness to infection by a gammaretrovirus that uses PiT-2 as a
      receptor. The distinct pattern of Pit2 expression during odontogenesis suggests
      that its P(i)-transporter function may be important for homeostasis of dental
      cells and not specifically for mineralization of the dental extracellular
      matrices. The expression of viral receptors in enamel-forming cells and the
      dental pulp may be of pathological significance.

PMID- 17184236
TI  - Formation of acellular cementum-like layers, with and without extrinsic fiber
      insertion, along inert bone surfaces of aging c-Src gene knockout mice.
AB  - To investigate the long-term effects of c-src deficiency on skeletal and dental
      tissues, we examined the lower jaws and long bones of c-src gene knockout (c-src
      KO) mice by histological and histochemical methods. Numerous multinucleated
      osteoclasts were distributed throughout the mandible in 5-wk-old c-src KO mice,
      but by 14 wk they had almost completely disappeared from the alveolar bone,
      leaving tartrate-resistant acid phosphatase (TRAP)-positive layers along the bone
      surface. Deposition of osteopontin-positive mineralized tissue, reminiscent of
      acellular afibrillar cementum (AAC), was confirmed along the TRAP-positive bone
      surface at 14 wk. The layer progressively thickened up to 21 months. A comparable
      mineralized layer was noted along the trabeculae of long bones as thickened
      cement lines. In the periostin-rich areas of jaw bones, but not in the long
      bones, portions of AAC-like mineralized layers were often replaced with and/or
      covered by acellular extrinsic fiber cementum (AEFC)-like tissue. These data
      suggest that the deposition of AAC-like mineralized tissue is a general
      phenomenon that may occur along inert or slowly remodeling bone surfaces under
      conditions characterized by reduced bone-resorbing activity, whereas the
      induction of AEFC-like tissue seems to be associated with the expression of
      certain molecules that are particularly abundant in the microenvironment of the
      periodontal ligament.

PMID- 17184237
TI  - Class II restorations: influence of a liner with rubbery qualities on the
      occurrence and size of cervical gaps.
AB  - The aim of this study was to evaluate the ability of new rubbery liners, used as
      a cervical increment, to relieve contraction stress and thereby reduce the
      formation of cervical gaps in class II composite restorations. The investigated
      liners were made of polyester-acrylate (PE(1), PE(2) or PE(3)) or silicone
      acrylate (S), mixed with UDMA, without (A, B, C, D) or with HEMA (AH, BH, CH,
      DH). A silanized filler was added to the mixture, DH, to give composites with 20,
      40, 60, and 70% (w/w) of filler (DHF20, DHF40, DHF60, DHF70, respectively). The
      presence and width of cervical gaps were determined using a light microscope.
      Statistical analysis showed that six of the 12 rubbery liners (AH-DH, DHF20
      DHF40) significantly decreased gap formation in comparison with the control
      group. In addition, the polymerization shrinkage, flow, and strain capacity of
      these liners were measured and the influence of these factors on gap formation
      was examined. Two- and three-dimensional regression analyses showed significantly
      negative linear correlations between gap formation and strain capacity, and
      between gap formation and flow, and a significantly positive linear correlation
      between gap formation and shrinkage.

PMID- 17184238
TI  - Pigmented epithelioid melanocytoma.

PMID- 17184239
TI  - A case of Carney complex.

PMID- 17184240
TI  - Crystal storing histiocytosis of the skin associated with multiple myeloma.
AB  - BACKGROUND: Crystal storing histiocytosis (CSH) imitating rhabdomyoma is a very
      rare disease entity involving different tissues. The skin is involved in
      extremely rare cases. OBJECTIVES: To describe the clinical and histopathological
      characteristics in a patient with unusually extensive skin involvement.
      OBSERVATIONS: A 62-year-old woman presented with a large red infiltrated
      verrucosus lesion on the anterior aspect of the chest and on the neck. The skin
      biopsy revealed histiocytes throughout the whole dermis containing thin
      crystalloid structures in the cytoplasm. Upon histopathological examination,
      crystal-storing histiocytosis was diagnosed and consequently a hematological
      examination revealed multiple myeloma IgG Kappa. Skin involvement by CSH
      proceeded the diagnosis of multiple myeloma by 4 years. CONCLUSIONS: Phagocytosis
      of crystals of immunoglobulins by histiocytes (crystals storing histiocytosis) is
      a rare symptom associated most often with lymphoproliferative disease. The
      clinical picture is not characteristic, in the histopathologic picture it is
      striking similarity to rhabdomyoma. The skin involvement by crystal storing
      histiocytosis can be the first symptom of malignant lymphoma that can proceed the
      hematological malignancy by years.

PMID- 17184242
TI  - Peripheral T-cell lymphoma presenting as lipoatrophy and nodules.
AB  - BACKGROUND: Cutaneous lymphomas have many morphologic forms and clinical
      features. Lymphoma presents rarely with a constellation of nodules, panniculitis,
      and localized lipoatrophy. The histopathologic similarities of lymphoma and
      connective tissue disease panniculitis may create a diagnostic challenge.
      METHODS: We retrospectively reviewed the case of a 47-year-old man who presented
      15 years earlier with recurrent fevers, fatigue, tender subcutaneous nodules, and
      facial, trunk, and extremity lipoatrophy. RESULTS: Initial biopsy of a cutaneous
      nodule showed lymphohistiocytic panniculitis without atypical inflammatory cells.
      Serologic tests showed negative connective tissue serologies, yet the initial
      clinical impression was most consistent with lupus panniculitis. Initially, the
      patient was treated with oral prednisone; later, steroid-sparing agents were used
      with modest improvement evidenced by resolution of his systemic symptoms and
      stabilization of the cutaneous findings. A decade later, more pronounced facial
      lipoatrophy, new facial nodules, and posterior thigh pain developed. Laboratory
      testing showed leukopenia, elevated liver and muscle enzymes,
      hypertriglyceridemia, and a low level of high-density lipoprotein. Biopsy of a
      new chin nodule indicated peripheral T-cell lymphoma, whereas an evaluation for
      systemic malignant involvement was negative. The patient was started on
      chemotherapy, which resulted in stabilization of the lipoatrophy and decreasing
      size and frequency of the cutaneous nodules, but the posterior thigh pain
      persisted. CONCLUSIONS: We report a rare case of lymphoma presenting as nodules
      and profound lipoatrophy, which exemplifies the complexity of lymphomas. Profound
      lipoatrophy and panniculitis may be an unusual and diagnostically challenging
      presentation of cutaneous lymphoma.

PMID- 17184241
TI  - Eosinophilic panniculitis: report of three cases.

PMID- 17184243
TI  - Regression of pustulosis palmaris et plantaris by periodontal treatment in a
      subject with severe periodontitis.

PMID- 17184244
TI  - Erythema annulare centrifugum in a HIV-positive patient.

PMID- 17184245
TI  - Pustular vasculitis disclosing a systemic lupus erythematosus.

PMID- 17184246
TI  - Superficial cutaneous Trichosporon asahii infection in an immunocompetent host.

PMID- 17184247
TI  - Newborn with pseudohypoaldosteronism and miliaria rubra.

PMID- 17184248
TI  - Hair cuticle differences between Asian and Caucasian females.

PMID- 17184249
TI  - Correct diagnosis of current head lice infestation made by affected individuals
      from a hyperendemic area.

PMID- 17184250
TI  - A randomized, open-label, comparative study of oral doxycycline 100 mg vs. 5%
      topical benzoyl peroxide in the treatment of mild to moderate acne vulgaris.

PMID- 17184251
TI  - Calcinosis cutis in a newborn caused by minimal calcium gluconate extravasation.

PMID- 17184252
TI  - Treatment of advanced classic Kaposi's sarcoma with weekly low-dose paclitaxel
      therapy.

PMID- 17184253
TI  - Sports purpura.

PMID- 17184254
TI  - Mono-letter mnemonics in dermatology.

PMID- 17184255
TI  - Aggressive squamous cell carcinoma developing in a giant epidermal cyst of the
      abdomen.

PMID- 17184256
TI  - Itraconazole in the treatment of cutaneous leishmaniasis.

PMID- 17184257
TI  - Grading simple chronic paronychia and onycholysis.

PMID- 17184258
TI  - Glomeruloid hemangiomas localized to the skin of the trunk with no clinical
      features of POEMS syndrome.

PMID- 17184259
TI  - Diltiazem-associated photodistributed hyperpigmentation in an elderly Hispanic
      female.

PMID- 17184260
TI  - Kaposi's varicelliform eruption in a patient with phenytoin-induced drug rash.

PMID- 17184261
TI  - Lichen planus pemphigoides associated with ramipril.

PMID- 17184262
TI  - Pseudoporphyria.

PMID- 17184263
TI  - Cutaneous leishmaniasis.

PMID- 17184264
TI  - Pseudodominant inheritance with the G86R mutation in the ARS gene in Mal de
      Meleda.

PMID- 17184265
TI  - Group A streptococcal septic vasculitis in a child with dengue hemorrhagic fever.

PMID- 17184266
TI  - Two cases of acquired perforating dermatosis treated with doxycycline therapy.

PMID- 17184267
TI  - Generalized psoriasis induced by topical treatment of actinic keratosis with
      imiquimod.

PMID- 17184268
TI  - Eczematous dermatitis and prurigo nodularis confined to a Becker's nevus.

PMID- 17184269
TI  - Tuberculous gumma in a patient with cervical lymphadenitis.

PMID- 17184270
TI  - Manual lymph drainage reduces trapdoor effect in subcutaneous island pedicle
      flaps.

PMID- 17184271
TI  - Mnemonics in dermatology.

PMID- 17184272
TI  - Oral and cutaneous lichenoid reaction secondary to imatinib: report of two cases.

PMID- 17184273
TI  - Skin atrophy caused by thiocolchicoside injections.

PMID- 17184274
TI  - A patient with hyper-immunoglobulin E syndrome 25 years later.

PMID- 17184275
TI  - Dermatofibrosarcoma protuberans occurring in the site of prior leishmanization.

PMID- 17184276
TI  - Maggot-treated wounds follow normal wound healing phases.

PMID- 17184277
TI  - Pick-Herxheimer's acrodermatitis chronica atrophicans in an endemic area of
      Northern Italy.

PMID- 17184278
TI  - Cardio-facio-cutaneous syndrome with hemihidrosis: ectodermal dysplasias
      spectrum?

PMID- 17184279
TI  - Differential expression of Bcl-2, Bax, and CD95 in DNA repair-proficient and DNA
      repair-deficient basal cell carcinoma patients.

PMID- 17184280
TI  - Fibre retention osseous resective surgery: a novel conservative approach for
      pocket elimination.
AB  - AIM AND BACKGROUND: The position of the most apical inter-dental portion of the
      alveolar crest is classically used in osseous resective surgery (ORS) to
      establish the amount of the inter-proximal and buccal/lingual bone resection.
      Supracrestal fibres connected to the root cementum are always present coronal to
      the alveolar crest both in healthy and diseased sites. The aim of this paper is
      to report a novel surgical approach that combines the classical method of osseous
      resection with the gingival fibre retention technique. MATERIAL AND METHODS: A
      description of the surgical procedure in four steps is provided (flap design,
      marginal soft tissue removal and fibre retention, ORS, suture of the flap).
      RESULTS AND CONCLUSION: The proposed technique shifts the bottom of the defect in
      a more coronal position at the level of the connective tissue fibre attachment,
      establishing a more conservative supporting bone resection.

PMID- 17184281
TI  - Antifungal immunity and adjuvant cytokine immune enhancement in cancer patients
      with invasive fungal infections.
AB  - Invasive fungal infections are common in severely immunosuppressed patients with
      cancer and in recipients of haematopoietic transplants. Response to antifungal
      therapy alone is often inadequate. Pro-inflammatory cytokines are critical for
      promoting innate and adaptive cellular antifungal immune responses. Recombinant
      cytokines, including granulocyte-macrophage-colony stimulating factor and
      interferon-gamma, have been studied as adjuvant therapies for severely
      immunosuppressed cancer patients with difficult-to-treat invasive mycoses. The
      limited clinical experience to date shows a possible benefit of these cytokines,
      and further controlled clinical trials are needed to validate their routine use
      in cancer patients and stem-cell transplant recipients with invasive fungal
      infections who are likely to have a poor response to antifungal drug therapy.

PMID- 17184282
TI  - The emergence of antibiotic resistance by mutation.
AB  - The emergence of mutations in nucleic acids is one of the major factors
      underlying evolution, providing the working material for natural selection. Most
      bacteria are haploid for the vast majority of their genes and, coupled with
      typically short generation times, this allows mutations to emerge and accumulate
      rapidly, and to effect significant phenotypic changes in what is perceived to be
      real-time. Not least among these phenotypic changes are those associated with
      antibiotic resistance. Mechanisms of horizontal gene spread among bacterial
      strains or species are often considered to be the main mediators of antibiotic
      resistance. However, mutational resistance has been invaluable in studies of
      bacterial genetics, and also has primary clinical importance in certain bacterial
      species, such as Mycobacterium tuberculosis and Helicobacter pylori, or when
      considering resistance to particular antibiotics, especially to synthetic agents
      such as fluoroquinolones and oxazolidinones. In addition, mutation is essential
      for the continued evolution of acquired resistance genes and has, e.g., given
      rise to over 100 variants of the TEM family of beta-lactamases. Hypermutator
      strains of bacteria, which have mutations in genes affecting DNA repair and
      replication fidelity, have elevated mutation rates. Mutational resistance emerges
      de novo more readily in these hypermutable strains, and they also provide a
      suitable host background for the evolution of acquired resistance genes in vitro.
      In the clinical setting, hypermutator strains of Pseudomonas aeruginosa have been
      isolated from the lungs of cystic fibrosis patients, but a more general role for
      hypermutators in the emergence of clinically relevant antibiotic resistance in a
      wider variety of bacterial pathogens has not yet been proven.

PMID- 17184283
TI  - Control of human cytomegalovirus infection in patients infected with human
      immunodeficiency virus by high levels of specific CD8+ T-cells.
AB  - A new technique was used to simultaneously determine human cytomegalovirus (HCMV)
      specific CD4(+) and CD8(+) T-cells in highly active anti-retroviral therapy
      (HAART)-naive and HAART-treated patients infected with human immunodeficiency
      virus (HIV). HIV-infected patients with HCMV infection, but without HCMV disease,
      showed low numbers of HCMV-specific CD4(+) cells and high numbers of CD8(+) T
      cells, both before and during HAART. HIV-infected patients with HCMV disease had
      no HCMV-specific CD4(+) T-cells and extremely low levels of CD8(+) T-cells.
      Resolution of disease during HAART was associated with rescue of specific CD4(+)
      T-cells and a large increase in the specific CD8(+) T-cell count. Thus, HAART
      does not completely restore the normal immune function. In HIV-infected patients,
      sustained control of HCMV infection requires high frequencies of specific CD8(+)
      T-cells.

PMID- 17184284
TI  - A 1-year study of the epidemiology of hepatitis A virus in Tunisia.
AB  - This 1-year (September 2000 to August 2001) prospective study investigated the
      presence of hepatitis A virus (HAV) in the population of Monastir, Tunisia (86
      serum samples), in the influents and effluents of two wastewater treatment
      plants, and in shellfish harvested in the coastal areas of Monastir, Bizerte and
      Sfax (January 2001 to May 2001). The virus was detected by RT-PCR using primers
      targeted at the VP3-VP1 region. An epidemic of HAV infection was observed during
      the winter months, with a peak in January. The presence of the virus was
      relatively constant in the influents and effluents of the wastewater treatment
      plants, and the virus was found in shellfish from the Monastir area during the
      months of January and February. The genotype IA strain was recovered most
      frequently from human serum and wastewater samples. The observation that the peak
      of the epidemic was during the winter months suggests that transmission of HAV is
      related to climatic factors and, presumably, to shellfish consumption.

PMID- 17184285
TI  - The contribution of pharmacokinetic-pharmacodynamic modelling with Monte Carlo
      simulation to the development of susceptibility breakpoints for Neisseria
      meningitidis.
AB  - This study used pharmacokinetic-pharmacodynamic (PK-PD) modelling and MICs of 15
      antimicrobial agents, derived from testing a large international culture
      collection, to assist in the development of interpretative criteria, i.e.,
      breakpoints, for Neisseria meningitidis. PK parameters, protein binding,
      percentage penetration into cerebrospinal fluid (CSF), and the variability of
      these values, were extracted from the published literature for the 15 agents. PK
      PD parameters have not been developed specifically for N. meningitidis in animal
      or human studies. Thus, it was necessary to invoke PK-PD targets from other
      organisms that cause infections at similar sites. The PK-PD targets utilised
      were: time above the MIC for at least 50% of the dosing interval for all beta
      lactams, chloramphenicol, sulphafurazole and trimethoprim-sulphamethoxazole; an
      AUC/MIC ratio of >or=25 for the tetracyclines and macrolides; and an AUC/MIC
      ratio of >or=125 for the fluoroquinolones. A 10 000-subject Monte Carlo
      simulation was designed with the usual dosing regimens of each antimicrobial
      agent at MIC values of 0.03-64 mg/L in both serum and CSF. The PK-PD breakpoint
      was defined as the MIC at which the calculated target attainment was >or=95%.
      Using these assumptions, the proposed PK-PD breakpoints were: azithromycin, 0.125
      mg/L; doxycycline, 0.25 mg/L; cefotaxime, ciprofloxacin and levofloxacin, 0.5
      mg/L; penicillin G, meropenem, rifampicin, tetracycline and minocycline, 1 mg/L;
      chloramphenicol and sulphafurazole, 2 mg/L; and ampicillin, ceftriaxone and
      trimethoprim-sulphamethoxazole, 4 mg/L. Proposed PK-PD breakpoints applicable to
      CSF were: penicillin and cefotaxime, 0.06 mg/L; rifampicin, 0.125 mg/L;
      ceftriaxone, meropenem and trimethoprim-sulphamethoxazole, 0.25 mg/L; ampicillin,
      0.5 mg/L; and chloramphenicol, 1 mg/L.

PMID- 17184286
TI  - Evaluation of a commercial IgE ELISA in comparison with IgA and IgM ELISAs, IgG
      avidity assay and complement fixation for the diagnosis of acute toxoplasmosis.
AB  - A panel of sera from patients with known case histories representative of acute
      toxoplasmosis (primarily lymphadenopathy, n = 106), latent toxoplasmosis
      (asymptomatic, n = 368) and negative samples (n = 54) was used to evaluate the
      capacity of five serological tests to differentiate among patients with acute or
      latent toxoplasmosis and non-infected individuals. Positive IgA, IgE and IgM
      ELISA results and low IgG avidity and complement fixation test (CFT) titres of
      >or=256 were considered to be indicative of acute toxoplasmosis. The most
      sensitive methods were IgM ELISA (98.1%) and CFT (97.1%), albeit with low
      specificity (65.0% and 64.5%, respectively) and positive predictive values (43.3%
      and 42.7%, respectively). IgG avidity assay and IgE ELISA had the highest
      specificity (97.7% and 91.7%, respectively) and the highest positive predictive
      values (89.4% and 75.6%, respectively). The best association between serological
      results and clinical findings was obtained with IgE ELISA (86%, as expressed via
      Youden's index). In a subset of 259 samples categorised by the period between the
      onset of clinical symptoms and sampling, >50% of patients had enlarged lymph
      nodes for <4 months, despite a broad range of differences. However, IgM remained
      positive for 12-18 months, IgA for 6-9 months and IgE for 4-6 months. IgG avidity
      remained low for a maximum of 4 months, after which avidity increased despite the
      persistence of enlarged lymph nodes and a positive IgE assay. Detection of IgE
      appears to be a highly specific test for confirming the acute nature of
      Toxoplasma infections that have been detected by other sensitive methods.

PMID- 17184287
TI  - RNA polymerase beta-subunit gene (rpoB) sequence analysis for the identification
      of Bacteroides spp.
AB  - Partial rpoB sequences (317 bp) of 11 species of Bacteroides, two Porphyromonas
      spp. and two Prevotella spp. were compared to delineate the genetic relationships
      among Bacteroides and closely related anaerobic species. The high level of inter
      species sequence dissimilarities (7.6-20.8%) allowed the various Bacteroides spp.
      to be distinguished. The position of the Bacteroides distasonis and Bacteriodes
      merdae cluster in the rpoB tree was different from the position in the 16S rRNA
      gene tree. Based on rpoB sequence similarity and clustering in the rpoB tree, it
      was possible to correctly re-identify 80 clinical isolates of Bacteroides. In
      addition to two subgroups, cfiA-negative (division I) and cfiA-positive (division
      II), of Bacteroides fragilis isolates, two distinct subgroups were also found
      among Bacteroides ovatus and Bacteroides thetaiotaomicron isolates. Bacteroides
      genus-specific rpoB PCR and B. fragilis species-specific rpoB PCR allowed
      Bacteroides spp. to be differentiated from Porphyromonas and Prevotella spp., and
      also allowed B. fragilis to be differentiated from other non-fragilisBacteroides
      spp. included in the present study.

PMID- 17184288
TI  - High-throughput amplification fragment length polymorphism (htAFLP) analysis
      identifies genetic lineage markers but not complement phenotype-specific markers
      in Moraxella catarrhalis.
AB  - Comparative high-throughput amplified fragment length polymorphism (htAFLP)
      analysis was performed on a set of 25 complement-resistant and 23 complement
      sensitive isolates of Moraxella catarrhalis in order to determine whether there
      were complement phenotype-specific markers within this species. The htAFLP
      analysis used 21 primer-pair combinations, generating 41 364 individual fragments
      and 2273 fragment length polymorphisms, with an average of 862 polymorphisms per
      isolate. Analysis of polymorphism data clearly indicated the presence of two
      phylogenetic lineages and 40 (2%) lineage-specific polymorphisms. However,
      despite the presence of 361 (16%) statistically significant complement phenotype
      associated polymorphisms, no single marker was 100% complement phenotype
      specific. Furthermore, no complement phenotype-specific marker was found within
      different phylogenetic lineages. These findings agree with previous results
      indicating that the complement resistance phenotype within M. catarrhalis is
      probably defined by multiple genes, although not all of these genes may be
      present within all M. catarrhalis isolates.

PMID- 17184289
TI  - Significance of human beta-defensins in the epithelial lining fluid of patients
      with chronic lower respiratory tract infections.
AB  - Human beta-defensins (hBDs) are the most abundant antimicrobial peptides in
      epithelial cells, and function in the host immune system. Respiratory epithelial
      cells express hBDs to inhibit bacterial proliferation during respiratory tract
      infections. The aim of this study was to investigate the release of hBDs into the
      respiratory tract and their benefit as a host defence system in chronic
      Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1-hBD-4)
      were measured in the bronchial epithelial lining fluid (ELF) of nine patients
      with chronic lower respiratory tract infection caused by P. aeruginosa. Eight
      patients with idiopathic pulmonary fibrosis and eight volunteers free of
      pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic
      microsampling and hBD levels were measured by radioimmunoassays. The
      antimicrobial effects of hBDs were studied individually and in combination using
      an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD
      3 tended to be higher in patients with chronic lower respiratory tract infection
      than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of
      nine patients, respectively, but the hBD levels in controls were all below the
      limits of detection. All patients with infection caused by mucoid P. aeruginosa
      had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed
      a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial
      proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are
      pathophysiologically important in infections caused by mucoid strains of P.
      aeruginosa.

PMID- 17184290
TI  - Characterisation of macrolide-non-susceptible Streptococcus pneumoniae colonising
      children attending day-care centres in Athens, Greece during 2000 and 2003.
AB  - Nasopharyngeal Streptococcus pneumoniae isolates colonising young children are
      representative of isolates causing clinical disease. This study determined the
      frequency of macrolide-non-susceptible pneumococci, as well as their phenotypic
      and genotypic characteristics, among pneumococci collected during two cross
      sectional surveillance studies of the nasopharynx of 2847 children attending day
      care centres in the Athens metropolitan area during 2000 and 2003. In total, 227
      macrolide-non-susceptible pneumococcal isolates were studied. Increases in
      macrolide non-susceptibility, from 23% to 30.3% (p <0.05), and in macrolide and
      penicillin co-resistance, from 3.4% to 48.6% (p <0.001), were identified during
      the study period. The M resistance phenotype, associated with the presence of the
      mef(A)/(E) gene, predominated in both surveys, and isolates carrying both
      mef(A)/(E) and erm(AM) were identified, for the first time in Greece, among the
      isolates from the 2003 survey. Pulsed-field gel electrophoresis analysis of the
      isolates from the 2000 survey indicated the spread of a macrolide- and penicillin
      resistant clone among day-care centres. The serogroups identified most commonly
      in the study were 19F, 6A, 6B, 14 and 23F, suggesting that the theoretical
      protection of the seven-valent conjugate vaccine against macrolide-non
      susceptible isolates was c. 85% during both study periods.

PMID- 17184291
TI  - Comparison of clinical and environmental isolates of Legionella pneumophila
      obtained in the UK over 19 years.
AB  - Between January 1980 and December 1998, 3458 cases of Legionnaires' disease were
      reported to the national surveillance scheme in England and Wales. Of these, 463
      (13.4%) were reported as proven by culture and isolation of Legionella spp., with
      96.3% being Legionella pneumophila. Serogroup (Sgp), monoclonal antibody (mAb)
      subgrouping and restriction fragment length polymorphism (RFLP) analysis data
      were obtained for 321 (69.3%) of these, of which 284 were classified as being
      unrelated to any other isolate in the study. Typing data were also available for
      117 unrelated environmental isolates of L. pneumophila obtained from England and
      Wales, giving a total of 401 unrelated isolates in the study. Of the clinical
      isolates, 88.0% were Sgp1, compared with only 42.7% of environmental isolates (p
      <0.001); 79.6% of clinical isolates were subgrouped as mAb2+, compared with only
      12.8% of environmental isolates (p <0.001). RFLP typing identified 67 types among
      the 401 isolates, with clinical isolates showing significantly less diversity
      than environmental isolates (index of diversity (IOD) 0.944 vs. 0.958; p <0.05),
      with three RFLP types (1, 5 and 14) accounting for 40.0% of all clinical
      isolates. Combining the phenotypic and genotypic data resulted in 173 distinct
      phenons, with clinical isolates showing significantly less diversity than
      environmental isolates (IOD 0.964 vs. 0.996; p <0.01). Three phenons accounted
      for 30% of all clinical isolates. These data strongly suggest that some strains
      of L. pneumophila are more likely to cause human infection than would be expected
      from their distribution in the environment.

PMID- 17184292
TI  - Evaluation of the SAS Legionella Test, a new immunochromatographic assay for the
      detection of Legionella pneumophila serogroup 1 antigen in urine.
AB  - This study evaluated a new immunochromatographic assay (SAS Legionella Test) for
      its ability to detect Legionella pneumophila serogroup 1 antigen in urine.
      Results were compared with those obtained using the Binax Now urinary antigen
      test. Sensitivity and specificity were estimated as 82.9% and 99.0%,
      respectively, for the SAS Legionella Test, and 91.4% and 100%, respectively, for
      the Binax Now urinary antigen test. The sensitivity of both tests increased to
      97.1% (p 0.009) and 94.2% (p 0.7), respectively, if the tests were examined after
      1 h.

PMID- 17184293
TI  - Legionnaires' disease and gardening.
AB  - Legionella longbeachae was cultured from the sputum of a patient suffering from
      Legionnaires' disease. Source identification efforts included analysis of samples
      of potting soil from the patient's garden, and a genotypically indistinguishable
      strain of L. longbeachae was cultured from this material. Following examination
      of a national collection of Legionella isolates, two more patients with
      indistinguishable genotypes were identified. One of these patients had visited a
      garden centre in the same municipality in which the index patient had acquired
      his potting soil. The study demonstrated the value of systematic collection of
      identification data and patient isolates over a prolonged period.

PMID- 17184294
TI  - The persistence of humoral and cellular immunities more than three decades after
      smallpox vaccination.
AB  - This study assessed the persistence of humoral (neutralising antibody titre to
      vaccinia virus) and cellular (immediate vaccinia-specific interferon (IFN)-gamma
      producing T-cell) immunities to smallpox in a Korean population. Individuals who
      were vaccinated 25-60 years previously had higher neutralising antibody titres
      (geometric mean titre (GMT) 13.7; 95% CI 11.0-17.2) than vaccinia-naive
      individuals (GMT 6.7; 95% CI 5.5-8.0; p <0.001). However, there was no
      significant difference in cellular immunity between individuals vaccinated
      previously and vaccinia-naive individuals, and only 15% of the individuals
      vaccinated previously displayed an immediate IFN-gamma-producing effector-memory
      response in ELISPOT assays.

PMID- 17184295
TI  - Markers of human papillomavirus infection and their correlation with cervical
      dysplasia in human immunodeficiency virus-positive women.
AB  - Human papillomavirus (HPV) genotypes and HPV DNA load were analysed in cervical
      smears from 76 human immunodeficiency virus (HIV)-positive and 54 HIV-negative
      women. The prevalence of genotypes was similar for all women, with the exception
      of HPV62, which was over-represented in HIV-positive samples. HIV-positive women
      showed a higher prevalence of multiple genotypes that correlated neither with
      CD4(+) T-cell counts nor with cervical dysplasia. No significant differences were
      observed in terms of total or single-type HPV DNA load. The HPV DNA load in both
      HIV-positive and HIV-negative women was significantly higher in squamous intra
      epithelial lesions than in negative Pap smears.

PMID- 17184296
TI  - Transforming growth factor-beta1 polymorphisms in patients with brucellosis: an
      association between codon 10 and 25 polymorphisms and brucellosis.
AB  - This study examined the association between transforming growth factor (TGF)
      beta1 polymorphisms and brucellosis. The TGF-beta1 genotypes at codons 10 and 25
      were determined by an amplification refractory mutation system-PCR among 425
      brucellosis patients and 213 healthy volunteers. The frequencies of TGF-beta1
      codons 10 C and 25 G were significantly higher among patients than among
      controls, as was that of TGF-beta1 codon 10 C/C. The high-producer haplotype
      (CG/TG) was more frequent among patients than among controls. The findings
      suggest that genetic polymorphism in codons 10 and 25 of the TGF-beta1 gene might
      contribute to the development of brucellosis.

PMID- 17184297
TI  - Characterisation of invasive meningococcal isolates from Italian children and
      adolescents.
AB  - Meningococcal invasive disease is a life-threatening infection that affects
      mostly children and adolescents. The present study was performed during 2003-2005
      to compare the phenotypic characteristics of meningococcal isolates from these
      two main groups at risk with those of isolates from other age groups to assess
      whether strategies for treatment and prevention implemented elsewhere can also be
      applied in Italy. The results showed that serogroup C meningococci were
      predominant, and that a dramatic increase in the circulation of strains with
      decreased susceptibility to penicillin was associated mainly with a prevalent
      phenotype C:2b:P1.5,2, which belongs to the hyper-virulent ST8/A4 cluster.

PMID- 17184298
TI  - Prevalence and mechanisms of macrolide resistance among Staphylococcus
      epidermidis isolates from neutropenic patients in Tunisia.
AB  - The prevalence of macrolide-lincosamide-streptogramin (MLS) resistance phenotypes
      was determined among erythromycin-resistant Staphylococcus epidermidis isolates
      collected at the Bone Marrow Transplant Centre, Tunisia during 2002. The erm(A),
      erm(B), erm(C), msrA, mefA and icaA genes were detected by PCR. The vga, vgb and
      vat genes were amplified from pristinamycin-resistant isolates. The icaA gene was
      detected in 76.5% of 34 isolates examined in detail. The erm(C) (53%) and erm(A)
      (32%) genes predominated because of clonal dissemination, followed by msrA (15%).
      Gene distribution was related to the methicillin resistance pattern. The vga gene
      was present in combination with erm(A) in three isolates.

PMID- 17184299
TI  - Emergence of VanD-type vancomycin-resistant Enterococcus faecium in Stockholm,
      Sweden.
AB  - A vancomycin-resistant Enterococcus faecium isolate from the urine of a liver
      transplant patient in Stockholm was found to contain a vanD gene. The sequence of
      the vanD PCR product shared 100% identity with the vanD5 allele. The isolate was
      resistant to a relatively high level of vancomycin (128 mg/L) and a low level of
      teicoplanin (4 mg/L). This is the first VanD-type vancomycin-resistant E. faecium
      isolate reported in Sweden. The emergence of this strain reinforces the necessity
      of infection control efforts to interrupt the spread of these organisms.

PMID- 17184301
TI  - Reduction of blood culture contamination rate by an educational intervention.

PMID- 17184302
TI  - Contamination of catheter-drawn blood cultures.

PMID- 17184303
TI  - The specificity of the electroimmunotransfer blot assay for Taenia solium
      cysticercosis.

PMID- 17184307
TI  - Using guidelines for exercise in cardiac patients.

PMID- 17184306
TI  - AANP insomnia surveys: sleep uncovered.

PMID- 17184308
TI  - Evidence-based practice for school nurse practitioners.

PMID- 17184309
TI  - Heart disease prevention in women: promoting exercise.
AB  - PURPOSE: To reinforce the importance of exercise in reducing heart disease in
      women and to describe motivational interviewing (MI), an effective and efficient
      approach to promoting exercise with women in a brief office visit with a nurse
      practitioner (NP). DATA SOURCES: Information was obtained from a literature
      review. Two brief examples from clinical practice are presented. CONCLUSIONS:
      Although exercise can reduce the risk of heart disease in women, most women do
      not exercise enough to achieve a risk reduction. Although health promotion is a
      key goal of the NP, it can be difficult to incorporate in a busy practice. When
      time is limited, brief MI interactions can be effective in less than 10 min, and
      the results surpass those of the traditional advice to exercise. IMPLICATIONS FOR
      PRACTICE: MI is an effective approach to exercise counseling that the NP can
      quickly learn and successfully conduct within the confines of a brief office
      visit.

PMID- 17184310
TI  - Predictors of poor coronary heart disease knowledge level in women without prior
      coronary heart disease.
AB  - PURPOSE: The purpose of this study was to measure coronary heart disease (CHD)
      knowledge levels in women without a history of CHD and to determine predictors of
      poor CHD knowledge in these women. DATA SOURCES: The sample included 120 women
      between the ages of 35 and 60, who had no CHD history. Women were asked to
      complete self-administered surveys including demographic data, personal CHD risk
      factors, and a CHD Knowledge Test. CONCLUSIONS: Women lack CHD knowledge. Low
      educational level, normal serum lipids, high body mass index (BMI), and lack of
      access to a nurse practitioner (NP) were predictors of poor CHD knowledge levels
      in women without CHD history. IMPLICATIONS FOR PRACTICE: Women who had access to
      an NP were more likely to have higher CHD knowledge. In an attempt to decrease
      the morbidity and mortality associated with CHD, NPs may be able to improve CHD
      knowledge in women, particularly in those with lower educational level, normal
      serum lipids and higher BMI.

PMID- 17184311
TI  - Integrating practice issues in managed care into the curriculum: a Delphi survey.
AB  - PURPOSE: This project evolved from a partnership between an advanced practice
      nurse (APN) graduate program and a care management insurer. The purpose of this
      Delphi survey was to identify (a) role components germane to the practice of APNs
      in managed care and (b) topics reflecting these components in the curriculum.
      DATA SOURCES: Data were gathered from two expert panels, clinician preceptors and
      faculty members. Each panel had 11 members: 11.3% and 100%, respectively, of the
      target populations of clinicians and faculty in the partnering agencies.
      CONCLUSIONS: There was considerable congruence between the panels on the survey.
      IMPLICATIONS FOR PRACTICE: Case vignettes could be used as a vehicle for
      discussion of the broader issues of population approaches to specific problems.
      Faculty could partner with clinicians to develop cases for discussion of evidence
      based practice. Faculty and clinicians could create preceptorships focused on
      business management, postgraduate fellowships within managed care systems, and
      regular opportunities to dialogue about curriculum and essential attributes of
      APN graduates.

PMID- 17184312
TI  - Antibiotic-taking experiences of undergraduate college students.
AB  - PURPOSE: The purpose of this qualitative descriptive study was to explore the
      medication-taking experiences of undergraduate college students prescribed short
      term antibiotic therapies and to describe factors influencing their adherence.
      DATA SOURCES: Thirty-four undergraduate students prescribed antibiotics for
      treatment of an acute infectious illness at a large university health center were
      recruited to participate in this study. Semistructured telephone interviews were
      conducted after students finished their course of treatment. Qualitative
      descriptive content analysis was used to analyze the transcripts typed from the
      audio-taped phone interviews. CONCLUSIONS: The main theme that emerged from the
      data was antibiotic-taking self-management. Most participants were able to adapt
      medication regimens into their daily routines, and used events in their day and
      specific reminder strategies to help them to remember to take their medications.
      This occurred despite an ever-changing class and work schedule and being
      prescribed complex, lengthy antibiotic regimens. Most dosing errors occurred
      during times when schedules changed or students were off campus during weekends
      or college breaks. A small number of students discontinued therapy early because
      of side effects or forgetfulness. IMPLICATIONS FOR PRACTICE: By understanding
      factors that influence antibiotic adherence from a college student perspective,
      healthcare providers can suggest strategies to promote adherence that are
      tailored to the specific needs of this unique population.

PMID- 17184314
TI  - Internal amplification controls have not been employed in fungal PCR hence
      potential false negative results.
AB  - Polymerase chain reaction (PCR) is subject to false negative results. Samples of
      fungi with the genes of interest (e.g. a disease or mycotoxin) may be categorized
      as negative and safe as a consequence. Fungi are eukaryotic organisms that are
      involved in many fields of human activity such as antibiotic, toxin and food
      production. Certain taxa are implicated in human, animal and plant diseases.
      However, fungi are difficult to identify and PCR techniques have been proposed
      increasingly for this purpose. Internal amplification controls (IACs) will
      ameliorate the situation and need to become mandatory. These are nucleic acids
      that posses a sequence which will provide a PCR product (i) using the same
      primers employed for the target gene, and (ii) that will not coincide on the gel
      with the product of the target gene. Only one group of workers employed an IAC,
      to respond to potential inhibition, which was reported in 1995 from this present
      assessment of numerous reports. Inhibitors in cultures need to be minimized, and
      secondary metabolites are an obvious source. The fields reviewed herein include
      medical mycology, mycotoxicology, environmental mycology and plant mycology. The
      conclusion is that previous reports are compromised because IACs have not been
      employed in fungal PCR; future research must include this control at an early
      stage.

PMID- 17184315
TI  - Virulent spores of Bacillus anthracis and other Bacillus species deposited on
      solid surfaces have similar sensitivity to chemical decontaminants.
AB  - AIMS: To compare the relative sensitivity of Bacillus anthracis and spores of
      other Bacillus spp. deposited on different solid surfaces to inactivation by
      liquid chemical disinfecting agents. METHODS AND RESULTS: We prepared under
      similar conditions spores from five different virulent and three attenuated
      strains of B. anthracis, as well as spores of Bacillus subtilis, Bacillus
      atrophaeus (previously known as Bacillus globigii), Bacillus cereus, Bacillus
      thuringiensis and Bacillus megaterium. As spore-surface interactions may bias
      inactivation experiments, we evaluated the relative binding of different spores
      to carrier materials. The survival of spores deposited on glass, metallic or
      polymeric surfaces were quantitatively measured by ASTM standard method E-2414-05
      which recovers spores from surfaces by increasing stringency. The number of
      spores inactivated by each decontaminant was similar and generally within 1 log
      among the 12 different Bacillus strains tested. This similarity among Bacillus
      strains and species was observed through a range of sporicidal efficacy on spores
      deposited on painted metal, polymeric rubber or glass. CONCLUSIONS: The data
      obtained indicate that the sensitivity of common simulants (B. atrophaeus and B.
      subtilis), as well as spores of B. cereus, B. thuringiensis, and B. megaterium,
      to inactivation by products that contain either: peroxide, chlorine or oxidants
      is similar to that shown by spores from all eight B. anthracis strains studied.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The comparative results of the present
      study suggest that decontamination and sterilization data obtained with simulants
      can be safely extrapolated to virulent spores of B. anthracis. Thus, valid
      conclusions on sporicidal efficacy could be drawn from safer and less costly
      experiments employing non-pathogenic spore simulants.

PMID- 17184316
TI  - Immune effect of heat-killed multistrain of Lactobacillus acidophilus against
      Salmonella typhimurium invasion to mice.
AB  - AIMS: This study attempted to determine whether lactic acid bacteria (LAB) could
      have a better probiotic function when used as a multistrain mixture, i.e. Mix
      LAB, than when used as a monostrain. To this end, three strains of Lactobacillus
      acidophilus, specifically strain LAP5, LAF1 and LAH7, were heat-killed and mixed.
      This heat-killed Mix-LAB was used to evaluate the effectiveness of multistrain in
      inhibiting Salmonella invasion into cultured cells and into organs (spleen and
      liver) of live mice. METHODS AND RESULTS: BALB/c mice were orally administered
      with heat-killed Mix-LAB or sterile normal saline (control) for seven consecutive
      days and then challenged with orally administered Salmonella typhimurium on day
      8. Results showed that, at day 6 after the challenge, the mice which had received
      Mix-LAB exhibited lower rates (P < 0.05) of Salmonella invasion into liver and
      spleen than did the control mice. Also, before the Salmonella challenge, the
      serum tumour necrosis factor-alpha (TNF-alpha) levels were not significantly
      different (P > 0.05) between these two groups of mice. After the challenge,
      however, the serum TNF-alpha level was significantly elevated (P < 0.05) in the
      control group, but not significantly changed in the Mix-LAB fed mice. To
      investigate possible factors involved in heat-killed Mix-LABs antagonistic effect
      on Salmonella invasion of mouse organs, heat-killed single strain and Mix-LAB
      were evaluated for ability to inhibit Salmonella invasion into cultured human
      intestinal Int-407 and Caco-2 cells. Results showed that none of the heat-killed
      strains were able to protect these cultured cells from Salmonella invasion, even
      though strains of LAP5 and Mix-LAB were adherent to them. However, study of the
      activation of murine macrophage Raw 264.7 cells showed that heat-killed Mix-LAB
      stimulated TNF-alpha production, nitric oxide release, and increased phagocytic
      activity in macrophages. CONCLUSIONS: Our findings suggest that heat-killed Mix
      LAB can inhibit Salmonella invasion of mouse organs through the immunomodulating
      role of activated macrophage. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability
      of heat-killed Mix-LAB to prevent bacterial infection in mice was found to be
      more significant than that of viable monostrain. This effect may be due to the
      activation of the immune system rather than to the adherence of LAB to the
      intestine epithelium.

PMID- 17184317
TI  - Development of molecular techniques for detection of lymphocystis disease virus
      in different marine fish species.
AB  - AIMS: The development and evaluation of a protocol based on polymerase chain
      reaction (PCR) and nucleic acid hybridization techniques for the specific
      detection of lymphocystis disease virus (LCDV) in several marine fish species.
      METHODS AND RESULTS: The pair of primers for PCR, OBL3 and OBL4, was designed
      based on published nucleotide sequence (LCDV-1) and amplifies a fragment within
      the major capsid protein. The sensitivity was evaluated using DNA from purified
      viral particles, as well as from cells inoculated with several viral
      concentrations. The PCR combined with slot blot was the most sensitive
      methodology, detecting 2.5 ng of viral DNA. Using this methodology LCDV was
      detected at 5 days postinoculation from SAF-1 cells initially inoculated with 10(
      5) TCID(50) ml(-1). The combination of PCR with membrane hybridization has also
      been proved to be adequate to detect LCDV from apparently healthy carriers by
      means of caudal fin sample analysis. This asymptomatic infection was also
      demonstrated by classical virological methods (cell culture and immunoblot).
      CONCLUSIONS: The protocol described in this study allows the specific detection
      of LCDV, both in cell cultures and in fin homogenates from asymptomatic fish.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The detection of asymptomatic carriers by a
      rapid molecular method using caudal fin sampling, which does not imply animal
      killing, could be an important tool to control epizootics caused by LCDV, as fish
      could be analysed before their introduction and/or mobilization in farm
      facilities.

PMID- 17184318
TI  - The microbiological quality of hot water-washed broccoli florets and cut green
      beans.
AB  - AIMS: To determine the effect of hot water washing on the microbiological quality
      of cut broccoli florets and trimmed green beans. METHODS AND RESULTS: Broccoli
      florets and trimmed beans were washed for 90 s in tap water at either 20 degrees
      C or 52 degrees C and stored at 7 and 10 degrees C. The numbers of naturally
      occurring aerobic mesophilic organisms, Pseudomonas spp., Enterobacteriaceae,
      yeast and moulds and lactobacilli or lactic acid bacteria were enumerated at
      intervals for up to 2 weeks. The ability of Listeria monocytogenes, Bacillus
      cereus and Escherichia coli O157:H7 inoculated onto the tissue post heat
      treatment to survive or grow was also measured to mimic the effect of postprocess
      contamination. Using a hot wash treatment improved the initial appearance of the
      vegetables and resulted in a small, but significant, reduction in populations of
      all groups of endogenous flora measured. The number of yeast and moulds on the
      vegetables washed at 52 degrees C remained below the levels observed on the 20
      degrees C washed vegetables throughout the observation period, but Pseudomonas
      spp., lactobacilli and Enterobacteriaceae were better able to grow on the hot
      washed vegetables such that the counts at the end of storage were greater on hot
      washed than ambient-washed vegetables. All three of the pathogens tested were
      better able to grow on hot-washed broccoli and beans than on equivalent product
      washed at 20 degrees C. CONCLUSIONS: Hot water washing can be used to control
      enzymic browning or yeast and moulds growth but it can also allow more rapid and
      extensive growth by pathogens and spoilage organisms. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Reduced protection against growth by pathogens means that the hot wash
      treatment of vegetables should be used with caution and requires careful
      assessment of risk.

PMID- 17184319
TI  - Effect of high hydrostatic pressure on four genotypes of F-specific RNA
      bacteriophages.
AB  - AIMS: The pressure responses of four genotypes of F-specific RNA bacteriophages,
      f2, GA, Qbeta and SP, were evaluated with respect to pressure magnitude,
      treatment temperature and suspending medium. METHOD AND RESULTS: The pressure
      responses were studied with respect to pressure magnitude (350 to 600 MPa),
      treatment temperature (-10 to 50 degrees C) and suspending media. Phages f2 and
      GA had much higher pressure resistances than Qbeta and SP. Pressure resistances
      of Qbeta and SP were enhanced with increase in salt concentrations in the range
      of 350 to 600 MPa from -10 to 50 degrees C in PBS. Qbeta and SP had greater
      pressure resistances when suspended in phosphate-buffered saline (PBS) with added
      glucose (5%, w/w), UHT whole milk and Dulbecco's Modified Eagle's Medium plus 10%
      fetal bovine sera than they did in PBS. Two surfactants, sucrose laurate and
      monolaurin, and one chelating agent, ethylenediamine tetraacetic acid (EDTA),
      increased the pressure resistance of Qbeta and SP, but had modest effect on
      either f2 or GA. CONCLUSIONS: Four representative F-specific RNA bacteriophages,
      f2 (serotype I), GA (serotype II), Qbeta (serotype III) and SP (serotype IV)
      showed different resistances to hydrostatic pressure in the range of 350-600 MPa.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study screened for practical
      surrogates of HAV for validation of commercial high hydrostatic pressure
      processing.

PMID- 17184320
TI  - Relationships between the density of different indicator organisms on sheep and
      beef carcasses and in frozen beef and sheep meat.
AB  - AIM: To describe the relationship between the concentration of different
      indicator bacteria in red meat. METHODS AND RESULTS: Enumeration data for aerobic
      plate count (APC), Enterobacteriaceae, coliforms and Escherichia coli biotype I
      were analysed from an Australia-wide survey of beef carcasses, sheep carcasses,
      frozen beef and frozen sheep meat. In all commodities, there was only low-to
      moderate rank correlation (0.16-0.47) between concentration of APC and
      concentration of each Gram-negative indicator. Rank correlations between counts
      of Gram-negative indicators were much higher (0.47-0.92) especially when
      nondetections were excluded from analysis (0.78-0.94). Receiver-operator
      characteristics analysis showed that detection of coliforms can predict the
      presence of E. coli biotype I with almost 100% sensitivity but fails to predict
      absence in 2.7-8.5% of samples not containing E. coli biotype I. CONCLUSIONS:
      Enumeration of coliforms is a useful adjunct to enumeration of E. coli biotype I
      or Enterobacteriaceae in red meat. The density of coliforms or Enterobacteriaceae
      can be used to predict the presence or absence of E. coli biotype I, although
      when the latter is at low prevalence errors in positive test prediction can be
      large. SIGNIFICANCE AND IMPACT OF THE STUDY: A quantitative basis is provided for
      comparing the concentration of different indicator bacteria measured in the
      production, regulation and trade of red meat.

PMID- 17184322
TI  - Diversity of Colombian strains of Bacillus thuringiensis with insecticidal
      activity against dipteran and lepidopteran insects.
AB  - AIM: To evaluate the genetic and molecular diversity and insecticidal activity of
      Bacillus thuringiensis isolates from all the natural regions of Colombia. METHODS
      AND RESULTS: A total of 445 isolates from a collection of B. thuringiensis were
      characterized. The parasporal crystal morphology that was most abundant was
      bipyramidal (60%). Almost 10% of the isolates were toxic to Spodoptera frugiperda
      and 5.6% against Culex quinquefasciatus larvae. cry gene content determined by
      PCR indicated that 10.6% of the isolates contained cry1 genes and 1.1% contained
      cry2, cry4 or cry11 genes. Protein content of the parasporal crystal was
      determined by SDS-PAGE; 25 and 18 different protein profiles were found in
      isolates active against S. frugiperda and C. quinquefasciatus, respectively.
      CONCLUSIONS: Bacillus thuringiensis presents great genetic and molecular
      diversity even in isolates from the same soil sample. Moreover, the diversity and
      activity of the isolates might have a relationship with the geographical origin
      of the samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The results obtained here
      indicate that some of the B. thuringiensis isolates characterized in this study
      are potential control agents that could be used in programmes against mosquitoes
      and S. frugiperda.

PMID- 17184323
TI  - Growth and survival of non-O157:H7 Shiga-toxin-producing Escherichia coli in cow
      manure.
AB  - AIMS: The main objective of this study was to evaluate the behaviour of non
      O157:H7 Shiga-toxin-producing Escherichia coli (STEC) strains in cow manure.
      METHODS AND RESULTS: A mixture of eight green-fluorescent-protein-labelled STEC
      strains was inoculated around 10(6)-10(7) CFU g(-1) into four manure heaps. Two
      heaps were regularly turned and the two others remained unturned. STEC counts and
      physical parameters (temperature, pH, moisture content and oxido-reduction
      potential) were monitored for 1000 manure samples. The highest mean pH values
      were obtained near the surface at the base of all manure heaps. At the surface,
      the moisture content decreased from 76.5% to 42% in turned heaps. Temperatures
      reached 65 degrees C near the main body of all manure heaps, and only 35 degrees
      C near the superficial parts located at the base of them. These two sites (the
      centre and the base) were associated with D values for the STEC counts of 0.48
      and 2.39 days, respectively. We were able to detect STEC strains during 42 days
      in turned manure heaps and during at least 90 days in unturned ones. CONCLUSIONS:
      These results emphasize the long-term survival of non-O157:H7 STEC in cow manure.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Good management practices (e.g. turning)
      should be respected in order to minimize the risk of environmental contamination
      by STEC.

PMID- 17184321
TI  - Analysis of factors influencing the rate of germination of spores of Bacillus
      subtilis by very high pressure.
AB  - AIMS: To elucidate the factors that determine the rate of germination of Bacillus
      subtilis spores with very high pressure (VHP) and the mechanism of VHP
      germination. METHODS AND RESULTS: Spores of B. subtilis were germinated rapidly
      with a VHP of 500 MPa at 50 degrees C. This VHP germination did not require the
      spore's nutrient-germinant receptors, as found previously, and did not require
      diacylglycerylation of membrane proteins. However, the spore's pool of
      dipicolinic acid (DPA) was essential. Either of the two redundant enzymes that
      degrade the spore's peptidoglycan cortex, and thus allow completion of spore
      germination, was essential for completion of VHP germination. However, neither of
      these enzymes was needed for DPA release triggered by VHP treatment. Completion
      of spore germination as well as DPA release with VHP had an optimum temperature
      of approx. 60 degrees C, in contrast to an optimum temperature of 40 degrees C
      for germination with the moderately high pressure of 150 MPa. The rate of spore
      germination by VHP decreased approx. fourfold when the sporulation temperature
      increased from 23 degrees C to 44 degrees C, and decreased twofold when 1 mol l(
      1) salt was present in sporulation. However, large variations in levels of
      unsaturated fatty acids in the spore's inner membranes did not affect rates of
      VHP germination. Complete germination of spores by VHP was not inhibited
      significantly by killing of spores with several oxidizing agents, and was not
      inhibited by ethanol, octanol or o-chlorophenol at concentrations that abolish
      nutrient germination. Completion of spore germination by VHP was also inhibited
      by Hg(2+), but this ion did not inhibit DPA release caused by VHP. In contrast,
      dodecylamine, a surfactant that can trigger spore germination, strongly inhibited
      DPA release caused by VHP treatment. CONCLUSIONS: VHP does not cause spore
      germination by acting upon the spore's nutrient-germinant receptors, but by
      directly causing DPA release. This DPA release then leads to subsequent
      completion of germination. VHP likely acts on the spore's inner membrane to cause
      DPA release, targeting either a membrane protein or the membrane itself. However,
      the precise identity of this target is not yet clear. SIGNIFICANCE AND IMPACT OF
      THE STUDY: There is significant interest in the use of VHP to eliminate or reduce
      levels of bacterial spores in foods. As at least partial spore germination by
      pressure is almost certainly essential for subsequent spore killing, knowledge of
      factors involved and the mechanism of VHP germination are crucial to the
      understanding of spore killing by VHP. This work provides new insight into
      factors that can affect the rate of B. subtilis spore germination by VHP, and
      into the mechanism of VHP germination itself.

PMID- 17184324
TI  - Identification and serotyping of atypical Legionella pneumophila strains isolated
      from human and environmental sources.
AB  - AIMS: To validate identification methods for Legionella pneumophila strains that
      cannot be serotyped into the known serogroups and to characterize their antigenic
      diversity. METHODS AND RESULTS: Fifty L. pneumophila strains that could not be
      serogrouped, but which had been confirmed as L. pneumophila by mip gene
      sequencing, were further identified phenotypically. We used (i) MONOFLUO anti
      Legionella Staining Reagent (Bio-Rad) (50/50), (ii) an in-house prepared
      immunoblot assay for the detection of L. pneumophila- specific Mip protein
      epitope (50/50), (iii) fatty acid analysis using the Microbial Identifications
      System (MIDI) (47/50) and (iv) Oxoid agglutination tests (44/50). The serological
      diversity was further characterized by testing with five serogroup-cross-reactive
      monoclonal antibodies, resulting in nine phenons. CONCLUSIONS: The division of L.
      pneumophila into 15 serogroups does not reflect the serogroup heterogeneity.
      Results of these tests indicate that there are more serogroups. SIGNIFICANCE AND
      IMPACT OF THE STUDY: MONOFLUO anti-Legionella Staining Reagent is the only
      commercially available tool for identifying atypical strains of L. pneumophila.
      If necessary for epidemiological purposes, the antigenic heterogeneity of these
      strains can be analysed by monoclonal antibodies.

PMID- 17184325
TI  - Development of antioxidant activity in milk whey during fermentation with lactic
      acid bacteria.
AB  - AIMS: To investigate the production of antioxidant activity during fermentation
      with commonly used dairy starter cultures. Moreover, to study the development of
      antioxidant activity during fermentation, and the connection to proteolysis and
      bacterial growth. METHODS AND RESULTS: Antioxidant activity was measured by
      analysing the radical scavenging activity using a spectrophotometric
      decolorization assay and lipid peroxidation inhibition was assayed using
      liposomal model system with a fluorescence method. Milk was fermented with 25
      lactic acid bacterial (LAB) strains, and from these six strains, exhibiting the
      highest radical scavenging activity was selected for further investigation.
      Leuconostoc mesenteroides ssp. cremoris strains, Lactobacillus jensenii (ATCC
      25258) and Lactobacillus acidophilus (ATCC 4356) showed the highest activity with
      both the methods used. However, the radical scavenging activity was stronger than
      lipid peroxidation inhibition activity. The development of radical scavenging
      activity was connected to proteolysis with four strains. Molecular distribution
      profiles showed that fermentates with high scavenging activity also possessed a
      higher proportion of peptides in the molecular mass range of 4-20 kDa, while
      others had mostly large polypeptides and compounds below 4 kDa. In addition, the
      amount of hydrophobic amino acids was higher in these fermentates. CONCLUSIONS:
      The development of antioxidant activity was strain-specific characteristic. The
      development of radical scavengers was more connected to the simultaneous
      development of proteolysis whereas, lipid peroxidation inhibitory activity was
      related to bacterial growth. However, high radical scavenging activity was not
      directly connected to the high degree of proteolysis. SIGNIFICANCE AND IMPACT OF
      THE STUDY: To the best of our knowledge, this seems to be the first report, which
      screens possible antioxidant activity among most common dairy LAB strains. Use of
      such strains improve nutritional value of fermented dairy products.

PMID- 17184327
TI  - Aspergillus species producing ochratoxin A: isolation from vineyard soils and
      infection of Semillon bunches in Australia.
AB  - AIMS: The incidence of toxigenicity among Australian isolates of Aspergillus
      niger and Aspergillus carbonarius was assessed. Aspergillus rot and concomitant
      production of ochratoxin A (OA) in bunches inoculated with A. carbonarius were
      also investigated. METHODS AND RESULTS: Aspergillus niger and A. carbonarius were
      isolated from vineyard soils. Aspergillus niger was more widespread than A.
      carbonarius, and two restriction fragment length polymorphism types of A. niger,
      N and T, were present. Three of 113 A. niger isolates and all 33 A. carbonarius
      isolates produced OA. Aspergillus carbonarius was inoculated onto Semillon
      bunches with and without damage in the month before harvest. Damaged berries at
      greater than 12.3 (o) Bx were particularly susceptible to Aspergillus rot and
      production of OA, which was concentrated in severely mouldy berries. CONCLUSIONS:
      OA in Australian grapes results mainly from infection of berries by A.
      carbonarius. It is concentrated in discoloured, shrivelled berries. The potential
      for Aspergillus rot and OA production appears to commence after veraison and
      increase with berry damage and ripeness. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Minimizing damage to grapes between veraison and harvest significantly reduces
      Aspergillus rot and OA formation. Monitoring the extent of Aspergillus rot in
      bunches infected with toxigenic Aspergillus spp. may give some indication of OA
      contamination.

PMID- 17184328
TI  - Role of Pantoea agglomerans in opportunistic bacterial seed and boll rot of
      cotton (Gossypium hirsutum) grown in the field.
AB  - AIMS: To investigate the aetiology of seed and boll rot of cotton grown in South
      Carolina (SC). METHODS AND RESULTS: Bacteria were isolated from diseased locules
      of cotton bolls collected in a field in SC, USA and tested for the ability to
      cause comparable disease symptoms in greenhouse grown cotton fruit. Spontaneously
      generated rifampicin-resistant (Rif(r)) mutants of the isolates were used in
      confirmatory pathogenicity tests. Resistance to the antibiotic was both stable
      and effective in differentiating between an inoculated Rif(r) strain, rifampicin
      sensitive contaminants and/or endophytes. A series of inoculation methods was
      tested at various boll developmental stages and at different fruiting nodes on
      the plant. Field disease symptoms were reproduced by inoculating bolls at 2 weeks
      postanthesis with bacterial suspensions ranging from 10(3) to 10(6) CFU ml(-1).
      Pathogenic isolates were categorized as Pantoea agglomerans on the basis of
      phenotype testing, fatty acid profiling (similarity index = 0.94), and 16s
      ribosomal DNA sequence analysis (99% nucleotide identity). CONCLUSIONS: Pantoea
      agglomerans isolates from field-collected immature, diseased cotton caused
      comparable infection symptoms in greenhouse produced cotton fruit. SIGNIFICANCE
      AND IMPACT OF THE STUDY: In 1999, significant yield losses in SC cotton resulted
      from a previously unobserved seed and boll rot that has since been reported in
      other southeastern states. This study demonstrated a role of P. agglomerans in
      producing opportunistic bacterial seed and boll rot of cotton.

PMID- 17184329
TI  - Multilocus sequence typing of Campylobacter jejuni isolates from New South Wales,
      Australia.
AB  - AIMS: Multilocus sequence typing (MLST) was used to examine the diversity and
      population structure of Campylobacter jejuni isolates associated with sporadic
      cases of gastroenteritis in Australia, and to compare these isolates with those
      from elsewhere. METHODS AND RESULTS: A total of 153 Camp. jejuni isolates were
      genotyped. Forty sequence types (STs) were found, 19 of which were previously
      undescribed and 21 identified in other countries. The 19 newly described STs
      accounted for 43% of isolates, 16 of which were assigned to known clonal
      complexes. Eighty-eight percent of isolates were assigned to a total of 15 clonal
      complexes. Of these, four clonal complexes accounted for 60% of isolates. Three
      STs accounted for nearly 40% of all isolates and appeared to be endemic, while 21
      STs were represented by more than one isolate. Seven infections were acquired
      during international travel, and the associated isolates all had different STs,
      three of which were exclusive to the travel-acquired cases. Comparison of
      serotypes among isolates from clonal complexes revealed further diversity. Eight
      serotypes were identified among isolates from more than one clonal complex, while
      isolates from six clonal complexes displayed serotypes not previously associated
      with those clonal complexes. CONCLUSIONS: Multilocus sequence typing is a useful
      tool for the discrimination of subtypes and examination of the population
      structure of Camp. jejuni associated with sporadic infections. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study highlights the genotypic diversity of Camp.
      jejuni in Australia, demonstrating that STs causing disease have both a global
      and a local distribution evident from the typing of domestically and
      internationally acquired Camp. jejuni isolates.

PMID- 17184326
TI  - Quantitative evaluation of adhesion of lactobacilli isolated from human
      intestinal tissues to human colonic mucin using surface plasmon resonance
      (BIACORE assay).
AB  - AIMS: To isolate lactobacilli from the mucus layer of the human intestine and
      evaluate their adhesion abilities using a BIACORE assay. METHODS AND RESULTS:
      Thirty strains of lactobacilli were isolated from the mucus layer of normal human
      intestinal tissues using conventional plate culture. The strains were identified
      using homology comparisons of the 16S rDNA sequence to databases as Lactobacillus
      salivarius (26%), Lactobacillus fermentum (13%), Lactobacillus gasseri (10%),
      Lactobacillus paracasei (7%), Lactobacillus casei (3%), Lactobacillus mucosae
      (3%) and Lactobacillus plantarum (3%). Lactobacillus plantarum LA 318 shows the
      highest adhesion to human colonic mucin (HCM) using the BIACORE assay at 115.30
      +/- 12.37 resonance unit (RU). The adhesion of cell wall surface proteins from
      strain LA 318 was significantly higher to HCM than to bovine serum albumin (BSA;
      P < 0.05). CONCLUSIONS: We isolated 30 strains of lactobacilli. Lactobacillus
      salivarius was the predominant species of lactobacilli isolated in this study.
      The adhesion of strain LA 318 isolated from human transverse colon to its mucin
      was shown. The adhesion could be mediated by lectin-like components on the
      bacterial cell surface. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first
      study where lactobacilli were isolated from human intestinal tissues and shown to
      adhere to HCM.

PMID- 17184330
TI  - Mechanisms of heat inactivation in Salmonella serotype Typhimurium as affected by
      low water activity at different temperatures.
AB  - AIMS: To determine the effect of reduced water activity (a(w)) on thermal
      inactivation of Salmonella serotype Typhimurium at different temperatures and its
      mechanism. METHODS AND RESULTS: D-value determinations at a range of different
      temperatures showed that heating at reduced a(w) (0.94, produced by addition of
      glucose or sodium chloride to nutrient broth) was protective at temperatures
      above 53-55 degrees C but sensitizing below this temperature. Using selective
      enumeration media to determine injury, it was shown that at lower heating
      temperatures cells survived at high a(w) with cytoplasmic injury whereas at low
      a(w) these cells were killed. At higher temperatures ribosome degradation was a
      more important cause of death and was inhibited by low a(w) heating media thereby
      providing greater heat resistance. CONCLUSIONS: The observed change in behaviour
      reflects the different reactions responsible for thermal death at different
      temperatures and their different response to reduced a(w). SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work qualifies the previous assumption that reduced
      a(w) is protective and suggests that the efficacy of low temperature
      pasteurization regimes may be increased by reduced a(w).

PMID- 17184331
TI  - Both sulfate-reducing bacteria and Enterobacteriaceae take part in marine
      biocorrosion of carbon steel.
AB  - AIMS: In order to evaluate the part played in biocorrosion by microbial groups
      other than sulfate-reducing bacteria (SRB), we characterized the phylogenetic
      diversity of a corrosive marine biofilm attached to a harbour pile structure as
      well as to carbon steel surfaces (coupons) immersed in seawater for increasing
      time periods (1 and 8 months). We thus experimentally checked corroding abilities
      of defined species mixtures. METHODS AND RESULTS: Microbial community analysis
      was performed using both traditional cultivation techniques and polymerase chain
      reaction cloning-sequencing of 16S rRNA genes. Community structure of biofilms
      developing with time on immersed coupons tended to reach after 8 months, a steady
      state similar to the one observed on a harbour pile structure. Phylogenetic
      affiliations of isolates and cloned 16S rRNA genes (rrs) indicated that native
      biofilms (developing after 1-month immersion) were mainly colonized by gamma
      proteobacteria. Among these, Vibrio species were detected in majority with
      molecular methods while cultivation techniques revealed dominance of
      Enterobacteriaceae such as Citrobacter, Klebsiella and Proteus species.
      Conversely, in mature biofilms (8-month immersion and pile structure), SRB, and
      to a lesser extent, spirochaetes were dominant. CONCLUSIONS: Corroding activity
      detection assays confirmed that Enterobacteriaceae (members of the gamma
      proteobacteria) were involved in biocorrosion of metallic material in marine
      conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: In marine biofilms, metal
      corrosion may be initiated by Enterobacteriaceae.

PMID- 17184332
TI  - Die-off of Cryptosporidium parvum in soil and wastewater effluents.
AB  - AIMS: To determine the effect of biotic and abiotic components of soil on the
      viability and infectivity of Cryptosporidium parvum, and evaluate the suitability
      of viability tests as a surrogate for oocyst infectivity under various
      environmental settings. METHODS AND RESULTS: The die-off of C. parvum in
      saturated and dry loamy soil was monitored over time by immunofluorescence assay
      (IFA) and PCR to estimate oocysts viability and by cell culture to estimate
      oocysts infectivity. Pseudomonas aeruginosa activity resulted in digestion of the
      outer layer of the oocysts, as demonstrated by loss of the ability to react in
      IFA. Whereas, P. aeruginosa activity did not affect the DNA amplification by PCR.
      A 1-log reduction in the oocysts infectivity was observed at 30 degrees C in
      distilled water and in saturated soil while oocysts viability was unchanged.
      Incubation for 10 days in dry loamy soil at 32 degrees C resulted in a 3-log(10)
      reduction in their infectivity while no change of oocysts viability was recorded.
      CONCLUSIONS: Under low temperature, C. parvum oocysts may retain their
      infectivity for a long time. Soil desiccation and high temperatures enhance the
      die-off rate of C. parvum. SIGNIFICANCE AND IMPACT OF THE STUDY: Previous die-off
      studies of C. parvum used viability tests that do not necessarily reflect the
      oocyst infectivity. Under low temperatures, there was an agreement observed
      between viability and infectivity tests and oocysts retained their infectivity
      for a long time. Desiccation and high temperatures enhance the loss of
      infectivity of C. parvum. The presented die-off data have significant
      implications on the management of wastewater reuse in warm environments.

PMID- 17184333
TI  - Influence of anode pretreatment on its microbial colonization.
AB  - AIMS: To assess the influence of chemical treatment of the anode of a marine
      sediment biofuel cell (MSBFC) on the microbial diversity of the anode biofilm.
      METHODS AND RESULTS: A MSBFC was equipped with two graphite plate anodes, one
      pretreated by electrochemical oxidation in sulfuric acid and the other untreated.
      After 6 weeks of operation, 16S rRNA clone libraries were constructed from each
      anode biofilm. The pretreated anode exhibited a fourfold depletion in gamma
      proteobacteria, a fourfold enrichment in delta-proteobacteria, a sixfold increase
      in sulfate reducers, a fivefold enrichment in unclassified micro-organisms, and
      6% of the colonies were sulfur oxidizers while none were detected on the
      untreated anode. CONCLUSION: Anode pretreatment significantly affects the anode
      colonized microbial communities of MSBFCs. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The MSBFC is one of a new class of microbial fuel cells in which the anode is
      spontaneously colonized by a subset of micro-organisms indigenous to a complex
      anaerobic mixture (such as sewage and food processing effluents). These micro
      organisms utilize the anode as an oxidant, catalysing power generation by
      oxidizing fuel in the mixture and reducing the anode. This study reveals that
      pretreatment of the anode can greatly affect the composition of the microbial
      colony of such fuel cells.

PMID- 17184334
TI  - Microbial community dynamics during assays of harbour oil spill bioremediation: a
      microscale simulation study.
AB  - AIMS: Microcosm experiments simulating an oil spill event were performed to
      evaluate the response of the natural microbial community structure of Messina
      harbour seawater following the accidental load of petroleum. METHODS AND RESULTS:
      An experimental harbour seawater microcosm, supplemented with nutrients and crude
      oil, was monitored above 15 days in comparison with unpolluted ones (control
      microcosms). Bacterial cells were counted with a Live/Dead BacLight viability
      kit; leucine aminopeptidase, beta-glucosidase, alkaline phosphatase, lipase and
      esterase enzymes were measured using fluorogenic substrates. The microbial
      community dynamic was monitored by isolation of total RNA, RT-PCR amplification
      of 16S rRNA, cloning and sequencing. Oil addition stimulated an increase of the
      total bacterial abundance, leucine aminopeptidase and phosphatase activity rates,
      as well as a change in the community structure. This suggested a prompt response
      of micro-organisms to the load of petroleum hydrocarbons. CONCLUSIONS: The
      present study on the viability, specific composition and metabolic
      characteristics of the microbial community allows a more precise assessment of
      oil pollution. Both structural and functional parameters offer interesting
      perspectives as indicators to monitor changes caused by petroleum hydrocarbons.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A better knowledge of microbial structural
      successions at oil-polluted sites is essential for environmental bioremediation.
      Data obtained in microcosm studies improve our understanding of natural processes
      occurring during oil spills.

PMID- 17184335
TI  - Differential utilization of pyrene as the sole source of carbon by Bacillus
      subtilis and Pseudomonas aeruginosa strains: role of biosurfactants in enhancing
      bioavailability.
AB  - AIMS: Our goal is to compare the efficiency of utilization of pyrene as the sole
      source of carbon for growth and energy by two nonactinomycetous groups of
      bacteria viz., Bacillus subtilis DM-04 and Pseudomonas aeruginosa mucoid (M) and
      nonmucoid (NM) strains, isolated from a petroleum-contaminated soil sample of
      north-east India. METHODS AND RESULTS: Bacillus subtilis DM-04 and P. aeruginosa
      M and NM bacterial strains were capable of secreting biosurfactant in the culture
      medium while growing on pyrene and their pyrene utilizing efficiency was
      demonstrated by correlating the bacterial growth in the presence of pyrene as the
      sole source of carbon along with a concomitant decrease in pyrene content from
      the culture medium with respect to time. The biosurfactant secreted by the
      respective bacterial strains enhanced the apparent solubility of pyrene by
      factors of 5-7 and influenced the bacterial cell surface hydrophobicity resulting
      in higher uptake and utilization of pyrene by bacteria. The growth of B. subtilis
      DM-04 and P. aeruginosa M and NM strains at the expense of pyrene after 96 h
      showed an assimilation of about 48.0 +/- 1.1% (mean +/- SD) and 32.0 +/- 0.6%
      (mean +/- SD) of pyrene carbon, respectively, showing differences in metabolism
      of pyrene by these bacterial strains. CONCLUSIONS: Bacillus subtilis DM-04 strain
      exhibited higher utilization and cellular assimilation of pyrene compared with P.
      aeruginosa M and NM strains. Further, the biosurfactants produced by the bacteria
      under study are capable of enhancing the solubility of pyrene in aqueous media
      and can influence the cell surface hydrophobicity of the biosurfactant-producing
      strains that results in a higher uptake of pyrene. SIGNIFICANCE AND IMPACT OF THE
      STUDY: It may be suggested that the bacteria used in this study are suitable
      candidates for practical field application for effective in situ bioremediation
      of pyrene-contaminated sites.

PMID- 17184336
TI  - Enhancement of acid amylase production by an isolated Aspergillus awamori.
AB  - AIMS: Evaluation of the influence of fermentation components on extracellular
      acid amylase production by an isolated fungal strain Aspergillus awamori. METHODS
      AND RESULTS: Eight fungal metabolic influential factors, viz. soluble starch,
      corn steep liquor (CSL), casein, potassium dihydrogen phosphate (KH(2)PO(4)) and
      magnesium sulfate (MgSO(4) x 7H(2)O), pH, temperature and inoculum level were
      selected to optimize amylase production by A. awamori using fractional factorial
      design of Taguchi methodology. Significant improvement in acid amylase enzyme
      production (48%) was achieved. The optimized medium composition consisted of
      soluble starch--3%; CSL--0.5%; KH(2)PO(4)--0.125%; MgSO(4) x 7H(2)O--0.125%;
      casein--1.5% at pH 4.0 and temperature at 31 degrees C. CONCLUSION: Optimization
      of the components of the fermentation medium was carried out using fractional
      factorial design of Taguchi's L-18 orthogonal array. Based on the influence of
      interaction components of fermentation, these could be classified as the least
      significant and the most significant at individual and interaction levels. Least
      significant factors of individual level have higher interaction severity index
      and vice versa at enzyme production in this fungal strain. The pH of the medium
      and substrate (soluble starch) showed maximum production impact (60%) at
      optimized environment. Temperature and CSL were the least influential factors for
      acid amylase production. SIGNIFICANCE AND IMPACT OF THE STUDY: Acid amylase
      production by isolated A. awamori is influenced by the interaction of
      fermentation factors with fungal metabolism at individual and interaction levels.
      The pH of the fermentation medium and substrate concentration regulates maximum
      enzyme production process in this fungal strain.

PMID- 17184337
TI  - Enhancing cell survival of atrazine degrading Rhodococcus erythropolis NI86/21
      cells encapsulated in alginate beads.
AB  - AIMS: To develop a method to produce beads with encapsulated Rhodococcus
      erythropolis NI86/21 with high cell density, extended shelf life, ease of
      handling and good atrazine degradation capabilities in both liquid and in
      agricultural soil. METHODS AND RESULTS: Our findings show that the supplementary
      recovery step in nutrient broth media shortly after cell encapsulation
      facilitates cell survival in both wet and dry beads upon extended storage at 4
      degrees C. Air drying has little or no impact on encapsulated R. erythropolis
      cell's ability to degrade atrazine in liquid or soil. Bead storage for periods
      extending up to 12 months at 4 degrees C did not affect the capacity of R.
      erythropolis encapsulated cells to degrade atrazine in either BMN or nonsterile
      soil extracts. Bentonite-amended beads formulated with 1% skim milk and exposed
      to the supplementary growth step, outperformed all other bead formats. These
      beads provided adequate numbers of vigorous R. erythropolis cells in either
      liquid or soil media to degrade atrazine. CONCLUSIONS: Supplementary growth in
      nutrient broth media immediately following cell encapsulation greatly enhances R.
      erythropolis cells survival in both wet and dry beads upon extended storage at 4
      degrees C. Wet and dried beads have similar capacity for atrazine degradation,
      and their usefulness and appeal in agronomic practise will only be known after
      bioassay evaluation and successful demonstration at field scale using incurred
      residues. SIGNIFICANCE AND IMPACT OF THE STUDY: R. erythropolis NI86/21
      encapsulated cells have the potential to reduce residual atrazine in soil,
      thereby minimizing the likelihood of off-site transport to ground or river water
      and reduce the loss of crops because of phytotoxicity of residual herbicide.
      Owing to their ease of handling, storage and possible compatibilities with pre
      existing mechanical equipment, dried bead formats are ideally suited for
      agricultural and remediational applications.

PMID- 17184338
TI  - Enhanced degradation and toxicity reduction of dihexyl phthalate by Fusarium
      oxysporum f. sp. pisi cutinase.
AB  - AIMS: This research aims to investigate the efficiency of two lipolytic enzymes-
      fungal cutinase and yeast esterase--upon the biodegradation of dihexyl phthalate
      (DHP). METHOD AND RESULTS: During the enzymatic degradation of DHP dissolved in
      methanol, several degradation products were detected and their time-course
      changes were monitored using GC/MS. The DHP-degradation rate of cutinase was
      surprisingly high; i.e. almost 70% of the initial DHP (500 mg l(-1)) was
      decomposed within 4.5 h. Although the same amount of esterase was employed, more
      than 85% of the DHP remained after 3 days. Almost all the DHP was converted by
      cutinase into 1,3-isobenzofurandione (IBF), whereas hexyl methyl phthalate and
      IBF were abundantly produced by esterase. In addition, the toxicities of the DHP
      degraded products by esterase were evaluated using various recombinant
      bioluminescent bacteria, which caused oxidative and protein damage, whereas the
      hydrolysis products from cutinase never caused any cellular damage in the
      methanol-containing reaction system. CONCLUSIONS: Cutinase starts to act as a DHP
      degrader much earlier and faster than esterase, with high stability in ester
      hydrolytic activity, therefore a plausible approach to the practical application
      of cutinase for DHP degradation in the DHP-contaminated environments may be
      possible. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes the enhanced
      degradation and detoxification of DHP using Fusarium oxysporum f. sp. pisi
      cutinase.

PMID- 17184339
TI  - Comparison of different biochemical and molecular methods for the identification
      of Vibrio parahaemolyticus.
AB  - AIMS: Multicentre evaluation of biochemical and molecular methods for the
      identification of Vibrio parahaemolyticus. METHODS AND RESULTS: For the
      biochemical identification methods, API 20E and API 20NE and Alsina's scheme were
      evaluated in intra- and interlaboratory tests in order to determine the accuracy
      and concordance of each method. Both in intra- and interlaboratory tests, the
      Alsina's scheme showed the highest sensitivity (86% of correct identifications in
      the interlaboratory test). False-positive results were obtained by all methods
      (specificity was 95% for API 20E, 73% for API 20NE and 84% for Alsina's scheme)
      and concordance varied from 65% of API 20NE to 84% of API 20E. For the molecular
      identifications, polymerase chain reaction (PCR) for the detection of toxR gene,
      tl gene and pR72H fragment were tested on 30 strains by two laboratories. The PCR
      for toxR showed the highest inclusivity (96%), exclusivity (100%) and concordance
      (97%). CONCLUSIONS: Among the biochemical identification methods tested, the
      Alsina's scheme gave more reliable results; however, in order to avoid false
      positive results, all the biochemical identifications should be confirmed by
      means of molecular methods. SIGNIFICANCE AND IMPACT OF THE STUDY: Availability of
      an efficient identification method of Vibrio parahaemolyticus to use in official
      control of fisheries products.

PMID- 17184340
TI  - Monitoring of staphylococcal starters in two French processing plants
      manufacturing dry fermented sausages.
AB  - AIMS: The growth and survival of Staphylococcus xylosus and Staphylococcus
      carnosus were monitored during sausage manufacture in two processing plants.
      METHODS AND RESULTS: The gram-positive, catalase-positive cocci isolated from the
      processing plants F10 and F11 were identified by Staphylococcus-specific PCR and
      species-specific oligonucleotide array. In the inoculated products with starter
      cultures, 90% of staphylococcal strains isolated in F10 were identified as S.
      xylosus and 10% as S. carnosus. In F11, 77% were identified as S. xylosus and 20%
      as S. carnosus. Staphylococcus xylosus dominated the staphylococcal microbiota
      while S. carnosus survived during the process. The pulse-field gel
      electrophoresis analysis revealed that all S. xylosus and S. carnosus strains
      isolated corresponded to the starter strains inoculated. The two starter strains
      of S. xylosus co-dominated in the isolates from sausages of F11, whereas the
      strain with pattern A1 was dominant in the isolates from sausages of F10. In the
      environments, no S. carnosus and S. xylosus were found, whereas Staphylococcus
      equorum and Staphylococcus saprophyticus were the main species isolated.
      CONCLUSIONS: This work highlighted the domination of S. xylosus starter strains,
      which showed a strong capacity to grow during sausage process, while S. carnosus
      survived during the process. SIGNIFICANCE AND IMPACT OF THE STUDY: Successful
      implantation of starter cultures is obviously a prerequisite for their
      contribution to sensorial qualities. Thus, the monitoring of the growth and the
      survival of S. xylosus and S. carnosus are required to guarantee a well-adapted
      starter culture. This study revealed that the two Staphylococcus species are
      suitable for manufacturing sausages in processing plants with very different
      capacities of production.

PMID- 17184341
TI  - PCR screening reveals unexpected antibiotic biosynthetic potential in
      Amycolatopsis sp. strain UM16.
AB  - AIMS: To assess the antibiotic biosynthetic potential of Amycolatopsis sp. strain
      UM16 and eight other Amycolatopsis species. METHODS AND RESULTS: Amycolatopsis
      genomic DNA was screened by PCR for the glycopeptide, Type-II (aromatic)
      polyketide and ansamycin biosynthetic gene clusters. Amycolatopsis sp. strain
      UM16, which exhibits weak antitubercular activity, was shown to have the
      glycopeptide oxyB gene and the Type-II (aromatic) polyketide-synthase KSalpha
      KSbeta tandem gene pair, but not the AHBA synthase gene. The ristocetin
      (glycopeptide) producer, Amycolatopsis lurida NRRL 2430(T), was shown to have the
      oxyB gene and the Type-II polyketide-synthase KSalpha-KSbeta tandem gene pair.
      Amycolatopsis alba NRRL 18532(T) was shown to have the glycopeptide oxyB gene and
      the AHBA synthase gene. Phylogenetic analyses using Amycolatopsis oxyB and
      KSalpha-KSbeta gene sequences were conducted. CONCLUSIONS: Amycolatopsis sp.
      strain UM16 appears to have the biosynthetic potential to produce glycopeptide
      and Type-II polyketide antibiotics, but not ansamycins. The potential to
      synthesize aromatic polyketides may be more widely distributed in Amycolatopsis
      than is currently recognized. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR screening
      is a very useful tool for rapidly identifying the biosynthetic potential of an
      antibiotic-producing actinomycete isolate. Advanced knowledge of the type of
      antibiotic(s) produced will allow appropriate methods to be selected for
      antibiotic purification.

PMID- 17184342
TI  - Characterization of extracellular polymers synthesized by tropical intertidal
      biofilm bacteria.
AB  - AIM: This study was performed to determine the potential of tropical intertidal
      biofilm bacteria as a source of novel exopolymers (EPS). METHODS AND RESULTS: A
      screening procedure was implemented to detect EPS-producing biofilm bacteria.
      Isolates MC3B-10 and MC6B-22, identified respectively as a Microbacterium species
      and Bacillus species by 16S rDNA and cellular fatty acids analyses, produced
      different EPS, as evidenced by colorimetric and gas chromatographic analyses. The
      polymer produced by isolate MC3B-10 displays significant surfactant activity, and
      may chelate calcium as evidenced by spectroscopic analysis. CONCLUSIONS: Polymer
      MC3B-10 appears to be a glycoprotein, while EPS MC6B-22 seems to be a true
      polysaccharide dominated by neutral sugars but with significant concentrations of
      uronic acids and hexosamines. EPS MC3B-10 possesses a higher surfactant activity
      than that of commercial surfactants, and given its anionic nature, may chelate
      cations thus proving useful in bioremediation. The chemical composition of
      polymer MC6B-22 suggests its potential biomedical application in tissue
      regeneration. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of a
      Microbacterium species producing EPS with surfactant properties, which expands
      our knowledge of the micro-organisms capable of producing these biomolecules.
      Furthermore, this work shows that tropical intertidal environments are a
      nonpreviously recognized habitat for bioprospecting EPS-producing bacteria, and
      that these molecules might be involved in ecological roles protecting the cells
      against dessication.

PMID- 17184343
TI  - Comparative analysis of environmental DNA extraction and purification methods
      from different humic acid-rich soils.
AB  - AIM: To establish a rapid, improved soil environmental DNA extraction and
      purification protocol. METHODS AND RESULTS: Three different soil DNA isolation
      and four purification strategies were compared on different soil samples with
      variable rates of success. Bead beating extraction gave significantly higher DNA
      yields than microwave-based and liquid nitrogen grinding DNA extraction methods.
      The inclusion of soil washing prior to cell lysis decreased the amount of
      purification steps required. Although these soil types differed,
      polyvinylpolypyrrolidone (PVPP)-sepharose 2B column elution was sufficient for
      all three samples, yielding DNA pure enough for successful application in
      molecular studies. One soil sample retained 80% of the initial DNA after
      successful purification. CONCLUSIONS: Optimization of a purification protocol
      confirmed that only a combination of previously described methods proved
      sufficient in yielding pure environmental DNA from humic-rich soils. Total
      processing time for DNA extraction and subsequent purification from multiple
      samples was considerably more rapid than the previously described methods.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study developed a new optimized soil
      DNA extraction and purification protocol that is suitable for different
      environmental sources that are rich in humic acid content.

PMID- 17184344
TI  - Partial characterization of bacteriocins produced by human Lactococcus lactis and
      Pediococccus acidilactici isolates.
AB  - AIMS: The aim of this study was to isolate bacteriocin-producing lactic acid
      bacteria (LAB) from human intestine. METHODS AND RESULTS: A total of 111 LAB were
      isolated from human adult stool and screened for their bacteriocin production.
      Neutralized cell-free supernatants from Lactococcus lactis subsp. lactis MM19 and
      Pediococcus acidilactici MM33 showed antimicrobial activity. The antimicrobials
      in the supernatant from a culture of L. lactis inhibited Enterococcus faecium,
      various species of Lactobacillus and Staphylococcus aureus; while those in the
      supernatant from a culture of P. acidilactici inhibited Enterococcus spp., some
      lactobacilli and various serotypes of Listeria monocytogenes. The antimicrobial
      metabolites were heat-stable and were active over a pH range of 2-10. The
      antimicrobial activities of the supernatants of both bacteria were inhibited by
      many proteases but not by catalase. The plate overlay assay allowed an
      approximation of size between 3.5 and 6 kDa for both antimicrobial substances.
      CONCLUSIONS: As the antagonistic factor(s) produced by L. lactis MM19 and P.
      acidilactici MM33 were sensitive to proteolytic enzymes, it could be hypothesized
      that bacteriocins were involved in the inhibitory activities. Inhibition spectrum
      and biochemical analysis showed that these bacteria produced two distinct
      bacteriocins. SIGNIFICANCE AND IMPACT OF THE STUDY: We are the first to isolate
      bacteriocin-producing strains of Pediococcus and Lactococcus from human
      intestine. These strains might be useful for control of enteric pathogens.

PMID- 17184345
TI  - In vitro and in vivo effects of hydrolysates from conglycinin on intestinal
      microbial community of mice after Escherichia coli infection.
AB  - AIMS: To detect the effect of pepsin-hydrolysate conglycinin (PTC) on the growth
      of Escherichia coli O(138)in vitro, and investigate the effect of PTC on
      intestinal microbial community of mice after E. coli infection. METHODS AND
      RESULTS: Serial dilution method was used to detect the antibacterial activity of
      PTC in 96-well cell-cultivated plates. Fifty-five KM mice were randomly assigned
      to five groups: normal, feeding-E. coli control, HCl-full hydrolysis of
      conglycinin, conglycinin and PTC. Orally administrated with hydrolysates from
      conglycinin for 21 days, each mouse was fed with 2 x 10(8) CFU ml(-1) of E. coli
      O(138) on the 22nd day. The mice activities were monitored and polymerase chain
      reaction-denaturing gradient gel electrophoresis was used to analyse the
      microbial community in mice faeces. The results showed that PTC could inhibit
      growth of E. coli O(138) at nitrogen concentrations of more than 520 mg l(-1).
      There was high similarity of intestinal microbial community in mice between PTC
      and normal groups. CONCLUSION: PTC inhibits growth of E. coli O(138), keeps mice
      healthy following oral administration of E. coli infection and maintains a
      balanced active microbial community in their gastrointestinal tract. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study demonstrated the antibacterial activity of
      PTC against E. coli and its ability to maintain healthy intestinal microbial
      community in mice even after they were infected with E. coli. This observation is
      significant in the application of PTC to prevent gastrointestinal diseases caused
      by E. coli and unbalanced intestinal microflora.

PMID- 17184346
TI  - A rapid PCR procedure for the specific identification of Lactobacillus
      sanfranciscensis, based on the 16S-23S intergenic spacer regions.
AB  - AIMS: The organization of ribosomal RNA (rrn) operons in Lactobacillus
      sanfranciscensis was studied in order to establish an easy-to-perform method for
      identification of L. sanfranciscensis strains, based on the length and sequence
      polymorphism of the 16S-23S rDNA intergenic spacer region (ISR). METHODS AND
      RESULTS: PCR amplification of the 16S-23S rDNA ISRs of L. sanfranciscensis gave
      three products distinguishing this micro-organism from the remaining
      Lactobacillus species. Sequence analysis revealed that two of the rrn operons
      were organized as in previously reported lactobacilli: large spacer (L-ISR),
      containing tRNA(Ile) and tRNA(Ala) genes; small spacer (S-ISR) without tRNA
      genes. The third described spacer (medium, M-ISR), original for L.
      sanfranciscensis, harboured a tRNA-like structure. An oligonucleotide sequence
      targeting the variable region between tDNA(Ile) and tDNA(Ala) of L.
      sanfranciscensis L-ISR was approved to be suitable in species-specific
      identification procedure. Analysis by pulse-field gel electrophoresis of the
      chromosomal digest with the enzyme I-CeuI showed the presence of seven rrn
      clusters. Lactobacillus sanfranciscensis genome size was estimated at c. 1.3 Mb.
      CONCLUSIONS: Direct amplification of 16S-23S ISRs or PCR with specific primer
      derived from L-ISR showed to be useful for specific typing of L.
      sanfranciscensis. This was due to the specific rrn operon organization of L.
      sanfranciscensis strains. SIGNIFICANCE AND IMPACT OF THE STUDY: In this paper, we
      have reported a rapid procedure for L. sanfranciscensis identification based on
      specific structures found in its rrn operon.

PMID- 17184347
TI  - Herbivore-induced plant volatiles as cues for habitat assessment by a foraging
      parasitoid.
AB  - 1. Animals usually require information about the current state of their habitat
      to optimize their behaviour. For this, they can use a learning process through
      which their estimate is continually updated according to the cues they perceive.
      Identifying these cues is a long-standing but still inveterate challenge for
      ecologists. 2. The use of plant cues by aphid parasitoids for the assessment of
      habitat profitability and the adaptation of patch exploitation was studied.
      Grounding on predictions from optimal foraging theory, we tested whether
      parasitoids exploited host patches less intensively after visiting heavily
      infested plants than after visiting plants bearing fewer aphids. 3. As predicted,
      after visiting heavily infested plants parasitoids reduced their residence time
      and attacked fewer hosts in the next patch. This was the case regardless of
      whether the aphids were actually present on the first plant, indicating that the
      cue came from the plant. Moreover, the level of infestation of a plant at some
      distance from the first plant visited affected parasitoid patch exploitation on
      the second plant in a similar manner, indicating that the cue was volatile. 4.
      These results highlight a novel role of herbivore-induced volatiles in parasitoid
      foraging behaviour, different from the widely studied attraction at a distance.

PMID- 17184348
TI  - At-sea distribution and scale-dependent foraging behaviour of petrels and
      albatrosses: a comparative study.
AB  - 1. In order to study and predict population distribution, it is crucial to
      identify and understand factors affecting individual movement decisions at
      different scales. Movements of foraging animals should be adjusted to the
      hierarchical spatial distribution of resources in the environment and this scale
      dependent response to environmental heterogeneity should differ according to the
      forager's characteristics and exploited habitats. 2. Using First-Passage Time
      analysis, we studied scales of search effort and habitat used by individuals of
      seven sympatric Indian Ocean Procellariiform species fitted with satellite
      transmitters. We characterized their search effort distribution and examined
      whether species differ in scale-dependent adjustments of their movements
      according to the marine environment exploited. 3. All species and almost all
      individuals (91% of 122 individuals) exhibited an Area-Restricted Search (ARS)
      during foraging. At a regional scale (1000s km), foraging ranges showed a large
      spatial overlap between species. At a smaller scale (100s km, at which an
      increase in search effort occurred), a segregation in environmental
      characteristics of ARS zones (where search effort is high) was found between
      species. 4. Spatial scales at which individuals increased their search effort
      differed between species and also between exploited habitats, indicating a
      similar movement adjustment for predators foraging in the same habitat. ARS zones
      of the two populations of wandering albatross Diomedea exulans (Crozet and
      Kerguelen) were similar in their adjustments (i.e. same ARS scale) as well as in
      their environmental characteristics. These two populations showed a weak spatial
      overlap in their foraging distribution, with males foraging in more southerly
      waters than females in both populations. 5. This study demonstrates that
      predators of several species adjust their foraging behaviour to the heterogeneous
      environment and these scale-dependent movement adjustments depend on both forager
      and environment characteristics.

PMID- 17184349
TI  - Prior knowledge about spatial pattern affects patch assessment rather than
      movement between patches in tactile-feeding mallard.
AB  - 1. Heterogeneity in food abundance allows a forager to concentrate foraging
      effort in patches that are rich in food. This might be problematic when food is
      cryptic, as the content of patches is unknown prior to foraging. In such case
      knowledge about the spatial pattern in the distribution of food might be
      beneficial as this enables a forager to estimate the content of surrounding
      patches. A forager can benefit from this pre-harvest information about the food
      distribution by regulating time in patches and/or movement between patches. 2. We
      conducted an experiment with mallard Anas platyrhynchos foraging in environments
      with random, regular, and clumped spatial configurations of full and empty
      patches. An assessment model was used to predict the time in patches for
      different spatial distributions, in which a mallard is predicted to remain in a
      patch until its potential intake rate drops to the average intake rate that can
      be achieved in the environment. A movement model was used to predict lengths of
      interpatch movements for different spatial distributions, in which a mallard is
      predicted to travel to the patch where it expects the highest intake rate. 3.
      Consistent with predictions, in the clumped distribution mallard spent less time
      in an empty patch when the previously visited neighbouring patch had been empty
      than when it had been full. This effect was not observed for the random
      distribution. This shows that mallard use pre-harvest information on spatial
      pattern to improve patch assessment. Patch assessment could not be evaluated for
      the regular distribution. 4. Movements that started in an empty patch were longer
      than movements that started in a full patch. Contrary to model predictions this
      effect was observed for all spatial distributions, rather than for the clumped
      distribution only. In this experiment mallard did not regulate movement in
      relation to pattern. 5. An explanation for the result that pre-harvest
      information on spatial pattern affected patch assessment rather than movement is
      that mallard move to the nearest patch where the expected intake rate is higher
      than the critical value, rather than to the patch where the highest intake rate
      is expected.

PMID- 17184350
TI  - Scale dependence of immigration rates: models, metrics and data.
AB  - 1. We examine the relationship between immigration rate and patch area for
      different types of movement behaviours and detection modes. Theoretical models
      suggest that the scale dependence of the immigration rate per unit area (I/A) can
      be described by a power model I/A = i*Area(zeta), where zeta describes the
      strength of the scale dependence. 2. Three types of scaling were identified. Area
      scaling (zeta = 0) is expected for passively dispersed organisms that have the
      same probability of landing anywhere in the patch. Perimeter scaling (-0.30 >
      zeta > -0.45) is expected when patches are detected from a very short distance
      and immigrants arrive over the patch boundary, whereas diameter scaling (zeta = 
      0.5) is expected if patches are detected from a long distance or if search is
      approximately linear. 3. A meta-analysis of published empirical studies of the
      scale dependence of immigration rates in terrestrial insects suggests that
      butterflies show diameter scaling, aphids show area scaling, and the scaling of
      beetle immigration is highly variable. We conclude that the scaling of
      immigration rates in many cases can be predicted from search behaviour and the
      mode of patch detection.

PMID- 17184351
TI  - Modelling population redistribution in a leaf beetle: an evaluation of
      alternative dispersal functions.
AB  - 1. Dispersal is a fundamental ecological process, so spatial models require
      realistic dispersal kernels. We compare five different forms for the dispersal
      kernel of the tansy beetle Chrysolina graminis moving between patches of its host
      plant (tansy Tanacetum vulgare) in a riparian landscape. 2. Multi-patch mark
      recapture data were collected every 2 weeks over 2 years within a large network
      of patches and from 2226 beetles. Dispersal was common (28.4% of 880 recaptures
      after a fortnight) and was more likely over longer intervals, out of small
      patches, for females and during flooding. Interpatch movement rates did not
      differ between years and exhibited no density dependence. Dispersal distances
      were similar for males and females, in both years and over all intervals, with a
      median dispersal distance of just 9.8 m, although a maximum of 856 m was
      recorded. 3. A model of dispersal, where patches competed for dispersers based on
      their size and distance from the beetle's source patch (scaled by the dispersal
      kernel) was fitted to the field data with a maximum likelihood procedure and each
      of five alternative kernels. The best fitting had relatively extended tails of
      long-distance dispersal, while Gaussian and negative exponential kernels
      performed worst. 4. The model suggests that females disperse more commonly than
      males and that both are strongly attracted to large patches but do not differ
      between years, which are consistent with the empirical results. Model-predicted
      emigration and immigration rates and dispersal phenologies match those observed,
      suggesting that the model captured the major drivers of tansy beetle dispersal.
      5. Although negative exponential and Gaussian kernels are widely used for their
      simplicity, we suggest that these should not be the models of automatic choice,
      and that fat-tailed kernels with relatively higher proportions of long-distance
      dispersal may be more realistic.

PMID- 17184352
TI  - A field test of simple dispersal models as predictors of movement in a cohort of
      lake-dwelling brook charr.
AB  - 1. Dispersal can be a major determinant of the distribution and abundance of
      animals, as well as a key mechanism linking behaviour to population dynamics, but
      progress in understanding dispersal has been hampered by the lack of a general
      framework for modelling dispersal. 2. This study tested the capacity of simple
      models to summarize and predict the lake-wide dispersal of an emerging cohort of
      young-of-the-year brook charr Salvelinus fontinalis, over 12 surveys conducted
      during a 2-month period. 3. The models are based on two types of dispersal
      kernel, the normal distribution from a simple diffusion process, and a Laplace
      distribution depicting exponential decay of the frequency of dispersers away from
      the point of origin. In all, four models were assessed: one-group diffusion (D1S)
      and exponential (E1S) models assuming homogeneous dispersal behaviour within the
      cohort, and two-group diffusion (D2S) and exponential (E2S) models accounting for
      intrapopulation differences in dispersal between sedentary and mobile
      individuals. 4. A rigorous cross-validation, based on calibrating the models to
      the distributions from the first two surveys only and then validating them on the
      remaining 10 distributions, was used to compare model predictions with observed
      values for five properties of the dispersal distributions: counts in individual
      shoreline sections; mean lateral displacement, variance and kurtosis of
      displacements; and the percentage of long-distance dispersers. 5. Substantial
      intrapopulation heterogeneity in dispersal behaviour was apparent: 83% of all
      individuals were estimated to be sedentary and the remainder mobile. Remarkably,
      the two-group exponential model E2S - calibrated to data from only two surveys
      conducted 3.5 and 8.5 days after the beginning of emergence - predicted
      reasonably well all properties of the spatial distribution of the cohort until
      the end of the study, 7 weeks later. 6. Standardized measures of mobility derived
      from simple models may lead to better understanding of population dynamics and
      improved management. Specifically, the ability to accurately predict long
      distance dispersal may be critical to assessing population persistence and cohort
      strength whenever key habitats, such as refugia or productive areas supporting a
      large proportion of the cohort, are sparsely distributed or distant from the
      point of origin.

PMID- 17184353
TI  - When trade-offs interact: balance of terror enforces dominance discovery trade
      off in a local ant assemblage.
AB  - 1. Trade-offs underpin local species coexistence. Trade-offs between interference
      and exploitative competitive ability provie a mechanism for explaining species
      coexistence within guilds that exploit overlapping resources. 2. Omnivorous, leaf
      litter ants exploit a shared food base and occur in species-rich assemblages. In
      these assemblages, species that excel at usurping food items from other species
      are poor at finding food items first. In assemblages where some members are
      attacked by phorid fly parasitoids, host species face an additional trade-off
      between defending themselves against parasitic attack and maximizing their
      competitive abilities. Host species thus face two trade-offs that interact via
      the trait-mediated indirect interaction generated by phorid defence behaviour. 3.
      In this study we test for the existence of these trade-offs and evaluate the
      predictions of a model for how they interact in an assemblage of woodland ants in
      which two behaviourally dominant members are attacked by phorid fly parasitoids
      as they attempt to harvest food resources. 4. The major findings are that
      unparasitized species in the assemblage follow a dominance-discovery trade-off
      curve. When not subject to attack by phorid flies, host species violate that
      trade-off by finding resources too quickly for their level of behavioural
      dominance. In contrast, when attacked by their phorid parasitoids, the host
      species dominance drops such that they fall into the assemblage trade-off. 5.
      These results match the predictions of the balance of terror model, which derives
      the optimal host response to parasitism, indicating that the host species balance
      the competing fitness costs of reduced competitive dominance and loss of workers
      to parasitism. This result supports the view that understanding the structure of
      ecological communities requires incorporating the indirect effects created by
      trait plasticity.

PMID- 17184354
TI  - Costs of coexistence along a gradient of competitor densities: an experiment with
      arvicoline rodents.
AB  - 1. Costs of coexistence for species with indirect resource competition usually
      increase monotonically with competitor numbers. Very little is known though about
      the shape of the cost function for species with direct interference competition.
      2. Here we report the results of an experiment with two vole species in
      artificial coexistence in large enclosures, where density of the dominant
      competitor species (Microtus agrestis) was manipulated. Experimental populations
      of the subordinate vole species (Clethrionomys glareolus) were composed of same
      aged individuals to study distribution of costs of coexistence with a dominant
      species within an age-cohort. 3. Survival and space use decreased gradually with
      increasing field vole numbers. Thus, responses to interference competition in our
      system appeared to be similar as expected from resource competition. The total
      number of breeders was stable. Reproductive characteristics such as the timing of
      breeding, and the litter size were not affected. In the single species enclosures
      a proportion of surviving individuals were not able to establish a breeding
      territory against stronger conspecifics. Under competition with heterospecifics
      such nonbreeders suffered high mortality, whereas the breeders survived. 4.
      Combined interference of dominant conspecifics and heterospecifics probably
      increased the frequency of aggressive interactions, social stress and mortality
      for the weaker individuals within a homogeneous age cohort of the subordinate
      competitor population. 5. Our results suggest, that in open systems where bank
      voles are outcompeted over the breeding season by faster reproducing field voles,
      animals able to establish a territory may be able to withstand competitor
      pressure, while nonbreeding bank vole individuals are forced to emigrate to
      suboptimal forest habitats.

PMID- 17184355
TI  - Measurement of body size and abundance in tests of macroecological and food web
      theory.
AB  - 1. Mean body mass (W) and mean numerical (N) or biomass (B) abundance are
      frequently used as variables to describe populations and species in
      macroecological and food web studies. 2. We investigate how the use of mean W and
      mean N or B, rather than other measures of W and/or accounting for the properties
      of all individuals, can affect the outcome of tests of macroecological and food
      web theory. 3. Theoretical and empirical analyses demonstrate that mean W, W at
      maximum biomass (W(mb)), W when energy requirements are greatest (W(me)) and the
      W when a species uses the greatest proportion of the energy available to all
      species in a W class (W(mpe)) are not consistently related. 4. For a population
      at equilibrium, relationships between mean W and W(me) depend on the slope b of
      the relationship between trophic level and W. For marine fishes, data show that b
      varies widely among species and thus mean W is an unreliable indicator of the
      role of a species in the food web. 5. Two different approaches, 'cross-species'
      and 'all individuals' have been used to estimate slopes of abundance-body mass
      relationships and to test the energetic equivalence hypothesis and related
      theory. The approaches, based on relationships between (1) log(10) mean W and
      log(10) mean N or B, and (2) log(10) W and log(10) N or B of all individuals
      binned into log(10) W classes (size spectra), give different slopes and
      confidence intervals with the same data. 6. Our results show that the 'all
      individuals' approach has the potential to provide more powerful tests of the
      energetic equivalence hypothesis and role of energy availability in determining
      slopes, but new theory and empirical analysis are needed to explain distributions
      of species relative abundance at W. 7. Biases introduced when working with mean W
      in macroecological and food web studies are greatest when species have
      indeterminate growth, when relationships between W and trophic level are strong
      and when the range of species'W is narrow.

PMID- 17184356
TI  - Two-species asymmetric competition: effects of age structure on intra- and
      interspecific interactions.
AB  - 1. The patterns of density-dependent resource competition and the mechanisms
      leading to competitive exclusion in an experimental two-species insect age
      structured interaction were investigated. 2. The modes of competition (scramble
      or contest) and strength of competition (under- to overcompensatory) operating
      within and between the stages of the two species was found to be influenced by
      total competitor density, the age structure of the competitor community and
      whether competition is between stages of single or two species. 3. The effect of
      imposed resource limitation on survival was found to be asymmetric between stages
      and species. Environments supporting both dominant and subordinate competitors
      were found to increase survival of subordinate competitors at lower total
      competitor densities. Competitive environments during development within
      individual stage cohorts (i.e. small or large larvae), differed from the
      competitive environment in lumped age classes (i.e. development from egg-
      >pupae). 4. Competition within mixed-age, stage or species cohorts, when compared
      with uniform-aged or species cohorts, altered the position of a competitive
      environment on the scramble-contest spectrum. In some cases the competitive
      environment switched from undercompensatory contest to overcompensatory scramble
      competition. 5. Such switching modes of competition suggest that the relative
      importance of the mechanisms regulating single-species population dynamics (i.e.
      resource competition) may change when organisms are embedded within a wider
      community.

PMID- 17184357
TI  - State-dependent invasion windows for prey in size-structured predator-prey
      systems: whole lake experiments.
AB  - 1. In size-structured communities where individuals grow in size over their life
      cycle, interactions between species will shift between competitive and predatory
      interactions depending on size relationships. The outcome of interactions will
      subsequently depend on the strength of competitive and predatory interactions,
      respectively. 2. In a whole lake experiment including four experimental lakes, it
      was tested under which conditions the competing prey, roach Rutilus rutilus,
      could successfully recruit into systems previously occupied by the predator,
      perch Perca fluviatilis. Two replicated introduction experiments were carried out
      3 years apart. 3. Roach were able to successfully recruit into three of the four
      experimental lakes of which two were also inhabited by the top predator pike Esox
      lucius. Resource levels were unrelated to whether roach could successfully
      recruit into the systems as recruiting roach in all years were feeding close to
      their maximum rate. 4. High population fecundity of roach and low predation
      pressure by perch combined were necessary ingredients for successful recruitment
      and the presence of only one of these conditions did not result in successful
      recruitment. 5. It is hypothesized that, although roach were able to successfully
      recruit into one lake with only perch present in addition to the two lakes that
      also inhabited pike, long-term coexistence of roach and perch depends on the
      presence of another top predator (e.g. pike) selectively preying on perch. This
      hypothesis was supported by data on co-occurrence of perch and roach in different
      lakes. 6. Overall, the results are in accordance with expectation of size
      structured life-history omnivory theory suggesting that coexistence between top
      predator and intermediate consumer is fragile.

PMID- 17184358
TI  - The macroecology of marine cleaning mutualisms.
AB  - 1. Marine cleaning mutualisms generally involve small fish or shrimps removing
      ectoparasites and other material from cooperating 'client' fish. We evaluate the
      role of fish abundance, body size and behaviour as determinants of interactions
      with cleaning mutualists. 2. Data come from eight reef locations in Brazil, the
      Caribbean, the Mediterranean and Australia. 3. We conducted a meta-analysis of
      client-cleaner interactions involving 11 cleaner and 221 client species. 4. There
      was a strong, positive effect of client abundance on cleaning frequency, but only
      a weak, negative effect of client body size. These effects were modulated by
      client trophic group and social behaviour. 5. This study adds to a growing body
      of evidence suggesting a central role of species abundance in structuring species
      interactions.

PMID- 17184359
TI  - Temporal dynamics and diversity of avian malaria parasites in a single host
      species.
AB  - 1. We have used molecular methods to unravel a remarkable diversity of parasite
      lineages in a long-term population study of great reed warblers Acrocephalus
      arundinaceus that was not foreseen from traditional microscopic examination of
      blood smears. This diversity includes eight Haemoproteus and 10 Plasmodium
      lineages of which most probably represent good biological species. 2. Contrary to
      expectation, the relative frequency of parasite lineages seemed not to change
      over the 17-year study period and we found no effects of the parasites on a male
      secondary sexual ornament (song repertoire size) and two measures of fitness
      (adult survival and production of recruited offspring). 3. We discuss whether the
      absence of fitness consequences of the parasites might relate to the fact that we
      have studied the host at the breeding sites in Europe, whereas the transmission
      seems to take place at the wintering sites in Africa, where the naive birds
      encounter the parasites for the first time and the resulting primary infections
      likely make them sicker than during the chronic phase of the infection. 4. The
      prevalence of the three most common lineages appeared to fluctuate in parallel
      with a periodicity of approximately 3-4 years. Theoretical models based on
      intrinsic interactions between parasite antigen and host immune genes cannot
      explain such dynamics, suggesting that knowledge of extrinsic parameters such as
      vector distribution and alternative hosts are required to understand these
      patterns.

PMID- 17184360
TI  - Abundance-occupancy dynamics in a human dominated environment: linking
      interspecific and intraspecific trends in British farmland and woodland birds.
AB  - 1. Range size, population size and body size, the key macroecological variables,
      vary temporally both within and across species in response to anthropogenic and
      natural environmental change. However, resulting temporal trends in the
      relationships between these variables (i.e. macroecological patterns) have
      received little attention. 2. Positive relationships between the local abundance
      and regional occupancy of species (abundance-occupancy relationships) are among
      the most pervasive of all macroecological patterns. In the absence of formal
      predictions of how abundance-occupancy relationships may vary temporally, we
      outline several scenarios of how changes in abundance within species might affect
      interspecific patterns. 3. We use data on the distribution and abundance of 73
      farmland and 55 woodland bird species in Britain over a 32-year period
      encompassing substantial habitat modification to assess the likelihood of these
      scenarios. 4. In both farmland and woodland habitats, the interspecific abundance
      occupancy relationship changed markedly over the period 1968-99, with a
      significant decline in the strength of the relationship. 5. Consideration of
      intraspecific dynamics shows that this has been due to a decoupling of abundance
      and occupancy particularly in rare and declining species. Insights into the
      intraspecific processes responsible for the interspecific trend are obtained by
      analysis of temporal trends in the distribution of individuals between sites,
      which show patterns consistent with habitat quality declines. 6. This study shows
      that a profitable approach to ascertaining the nature of human impacts is to link
      intra- and interspecific processes. In the case of British farmland and woodland
      birds, changes to the environment lead to species-specific responses in large
      scale distributions. These species-specific changes are the driver of the
      observed changes in the form and strength of the interspecific relationship.

PMID- 17184362
TI  - Spring temperature, clutch initiation date and duck nest success: a test of the
      mismatch hypothesis.
AB  - 1. Increases in average global temperature during the twentieth century have
      prompted calls for research on the effect of temperature variation on avian
      population dynamics. Particular attention has been paid to the hypothesis that
      increased temperatures may affect a species' ability to shift their breeding
      efforts to match the phenology of their prey, and thus result in reduced
      reproductive success (the 'mismatch hypothesis'). 2. We used data from a long
      term study of breeding ducks to investigate how duck nest success varied with
      clutch initiation date, and to test whether spring temperature affected this
      relationship in a manner consistent with the mismatch hypothesis. We modelled
      five possible functional forms of how nest success might vary with clutch
      initiation date and spring temperature, and used an information-theoretic
      approach to determine which model best described the nesting outcomes of five
      dabbling duck species nesting in Saskatchewan, Canada. 3. Probability of nest
      success for the five species did not vary strongly with clutch initiation date,
      and we found evidence consistent with the mismatch hypothesis for one species,
      northern pintail Anas acuta, although weight of evidence was weak. 4. Overall
      nest success of all five species was positively associated with spring
      temperature. These results suggest that increasing spring temperature alone
      (within the range observed in this study) may not affect nest success in a manner
      that would result in lower populations of breeding ducks.

PMID- 17184361
TI  - Is the shape of the density-growth relationship for stream salmonids evidence for
      exploitative rather than interference competition?
AB  - 1. Empirical studies show that average growth of stream-dwelling salmon and trout
      often declines with increasing density in a characteristic concave relationship.
      However, the mechanisms that generate negative density-growth relationships in
      populations in natural streams are not certain. 2. In a recent study, Imre, Grant
      & Cunjak (2005; Journal of Animal Ecology, 74, 508-516) argue that density
      dependent growth due to exploitative competition for prey causes the negative
      density-growth relationships for stream salmonids. They argue that the concave
      shape of empirical density-growth relationships is consistent with a simple model
      of exploitative competition and not consistent with interference competition for
      space. 3. We use a simple model to show that competition for space can yield
      concave density-growth relationships consistent with the empirical pattern when
      individuals compete for foraging sites that vary spatially in quality and lower
      quality sites predominate. Thus, the predictions of the exploitative competition
      and spatial competition models overlap. 4. The shape of the density-growth
      relationship does not differentiate between candidate mechanisms underlying
      density-dependent growth for stream salmonids. Our results highlight the general
      problem with determining the mechanism driving an ecological process from
      patterns in observational data within the context of linking population
      demographics to habitat structure and animal behaviour.

PMID- 17184363
TI  - Intraspecific competition and density dependence of food consumption and growth
      in Arctic charr.
AB  - 1. Intraspecific competition for restricted food resources is considered to play
      a fundamental part in density dependence of somatic growth and other population
      characteristics, but studies simultaneously addressing the interrelationships
      between population density, food acquisition and somatic growth have been
      missing. 2. We explored the food consumption and individual growth rates of
      Arctic charr Salvelinus alpinus in a long-term survey following a large-scale
      density manipulation experiment in a subarctic lake. 3. Prior to the initiation
      of the experiment, the population density was high and the somatic growth rates
      low, revealing a severely overcrowded and stunted fish population. 4. During the
      6-year period of stock depletion the population density of Arctic charr was
      reduced with about 75%, resulting in an almost twofold increase in food
      consumption rates and enhanced individual growth rates of the fish. 5. Over the
      decade following the density manipulation experiment, the population density
      gradually rose to intermediate levels, accompanied by corresponding reductions in
      food consumption and somatic growth rates. 6. The study revealed negative
      relationships with population density for both food consumption and individual
      growth rates, reflecting a strong positive correlation between quantitative food
      intake and somatic growth rates. 7. Both the growth and consumption rate
      relationships with population density were well described by negative power
      curves, suggesting that large density perturbations are necessary to induce
      improved feeding conditions and growth rates in stunted fish populations. 8. The
      findings demonstrate that quantitative food consumption represents the connective
      link between population density and individual growth rates, apparently being
      highly influenced by intraspecific competition for limited resources.

PMID- 17184364
TI  - Environmental variation and experience-related differences in the demography of
      the long-lived black-browed albatross.
AB  - 1. It has been largely demonstrated that demographic performances of animals
      increase with age or experience as a result of an improvement of foraging skills,
      an increasing reproductive effort or a selection process. However, little is
      known about the age or experience-related response of populations to
      environmental variations. Theoretical studies consider that age-related
      variations of the performances are greater under more restricting conditions, but
      this has rarely been tested. 2. We tested this hypothesis on a long-lived
      species, black browed albatross Thalassarche melanophrys Temminck, using a long
      term capture-mark-recapture data set. We investigated the responses of a
      population to climate, by studying the effects of climatic factors and breeding
      experience on survival and breeding success. 3. First-time breeders appear to be
      poorer performers compared with experienced adults, with lower reproductive
      success and lower survival. In addition, interannual variations of demographic
      traits were partly explained by climatic indices, reflecting environmental
      variations. The survival probability of black-browed albatrosses varied with
      experience and climate, and differences being greater under harsh conditions. By
      contrast, the reproductive success of inexperienced individuals was affected by
      climatic fluctuations in the same way as the experienced ones. 4. First breeding
      event acts as a strong selective process on the highly heterogeneous class of
      inexperienced individuals, suggesting the increase in survival and breeding
      success with experience may mainly reflect a reduction in the heterogeneity among
      individual qualities.

PMID- 17184365
TI  - The day after: effects of vocal interactions on territory defence in
      nightingales.
AB  - 1. Models on territory acquisition and tenure predict that territorial animals
      benefit by adjusting territorial defence behaviour to previous challenges they
      had experienced within the socially complex environment of communication
      networks. 2. Here, we addressed such issues of social cognition by investigating
      persisting effects of vocal contests on territory defence behaviour in
      nightingales Luscinia megarhynchos (Brehm). 3. Using interactive playback during
      nocturnal song of subjects, a rival was simulated to countersing either
      aggressively (by song overlapping) or moderately (by song alternating) from
      outside the subjects' territory. Thereby, the time-specific singing strategy
      provided an experimentally controlled source of information on the motivation of
      an unfamiliar rival. 4. Expecting that nightingales integrate information with
      time, the same rival was simulated to return as a moderately singing intruder on
      the following morning. 5. The results show that the vigour with which male
      nightingales responded to the simulated intrusion of an opponent during the day
      depended on the nature of the nocturnal vocal interaction experienced several
      hours before. 6. Males that had received the song overlapping playback the
      preceding night approached the simulated intruder more quickly and closer and
      sang more songs near the loudspeaker than did males that had received a song
      alternating playback. 7. This adjustment of territory defence strategies
      depending on information from prior signalling experience suggests that
      integrating information with time plays an important part in territory defence by
      affecting a male's decision making in a communication network.

PMID- 17184366
TI  - Maternal condition influences phenotypic selection on offspring.
AB  - 1. Environmentally induced maternal effects are known to affect offspring
      phenotype, and as a result, the dynamics and evolution of populations across a
      wide range of taxa. 2. In a field experiment, we manipulated maternal condition
      by altering food availability, a key factor influencing maternal energy
      allocation to offspring. We then examined how maternal condition at the time of
      gametogenesis affects the relationships among early life-history traits and
      survivorship during early development of the coral reef fish Pomacentrus
      amboinensis. 3. Maternal condition did not affect the number of embryos that
      hatched or the number of hatchlings surviving to a set time. 4. We found no
      significant difference in egg size in relation to the maternal physiological
      state. However, eggs spawned by supplemented mothers were provisioned with
      greater energy reserves (yolk-sac and oil globule size) than nonsupplemented
      counterparts, suggesting that provision of energy reserves rather than egg size
      more closely reflected the maternal environment. 5. Among offspring originating
      from supplemented mothers, those with larger yolk-sacs were more likely to
      successfully hatch and survive for longer periods after hatching. However, among
      offspring from nonsupplemented mothers, yolk-sac size was either inconsequential
      to survival or offspring with smaller yolk-sac sizes were favoured. Mothers
      appear to influence the physiological capacity of their progeny and in turn the
      efficiency of individual offspring to utilize endogenous reserves. 6. In summary,
      our results show that the maternal environment influences the relationship
      between offspring characteristics and survival and suggest that energy-driven
      selective mechanisms may operate to determine progeny viability.

PMID- 17184367
TI  - Recording the free-living behaviour of small-bodied, shallow-diving animals with
      data loggers.
AB  - 1. Time-depth data recorders (TDRs) have been widely used to explore the
      behaviour of relatively large, deep divers. However, little is known about the
      dive behaviour of small, shallow divers such as semi-aquatic mammals. 2. We used
      high-resolution TDRs to record the diving behaviour of American mink Mustela
      vison (weight of individuals 580-1275 g) in rivers in Oxfordshire (UK) between
      December 2005 and March 2006. 3. Dives to > 0.2 m were measured in all
      individuals (n = 6). Modal dive depth and duration were 0.3 m and 10 s,
      respectively, although dives up to 3 m and 60 s in duration were recorded. Dive
      duration increased with dive depth. 4. Temperature data recorded by TDRs covaried
      with diving behaviour: they were relatively cold (modal temperature 4-6 degrees C
      across individuals) when mink were diving and relatively warm (modal temperature
      24-36 degrees C across individuals) when mink were not diving. 5. Individuals
      differed hugely in their use of rivers, reflecting foraging plasticity across
      both terrestrial and aquatic environments. For some individuals there was < 1
      dive per day while for others there was > 100 dives per day. 6. We have shown it
      is now possible to record the diving behaviour of small free-living animals that
      only dive a few tens of centimetres, opening up the way for a new range of TDR
      studies on shallow diving species.

PMID- 17184368
TI  - Parasite survey of a Daphnia hybrid complex: host-specificity and environment
      determine infection.
AB  - 1. Hybridization between species is a common phenomenon in plants and animals. If
      parasite prevalence differs for hybrids and parental species (i.e. taxa) there
      may be considerable consequences for relative hybrid fitness. Some studies have
      investigated hybrid complexes for infection, and complex-specific differences in
      parasite prevalence have been detected. 2. Based on the results of a field study
      on a hybridizing Daphnia population from a single lake, it has been hypothesized
      that permanently over- or under-infected hybrids do not exist. The observed field
      patterns can only be temporal because taxa, in addition to single genotypes,
      might be the subject of parasite driven host frequency-dependent selection. Thus,
      parasites will track any common taxon within a hybrid complex. 3. In the present
      study, hybridizing Daphnia populations from 43 lakes were screened for parasite
      infections to obtain indirect evidence for coevolutionary cycles. It was
      hypothesized that, due to time lags between the evolution of resistance in host
      populations and the evolution of the parasite towards tracking of a common host
      taxon, the same Daphnia taxon will be over-infected in some lakes, while being
      under-infected in others. 4. Two of the four parasite species were specialists:
      their prevalence differed among coexisting Daphnia taxa. The varying infection
      patterns detected across spatially segregated hybridizing Daphnia populations are
      consistent with theoretical predictions for coevolutionary cycles. Thus the
      infection patterns, as observed under natural conditions, are temporal and
      unstable. 5. Additionally, the spatial distribution of the four parasite species
      was analysed with respect to habitat differences. The results show that the
      presence of a particular parasite on a host taxon was determined not only by the
      host-specificity of the parasite, but also by host-habitat relations.

PMID- 17184369
TI  - Sex and testosterone effects on growth, immunity and melanin coloration of
      nestling Eurasian kestrels.
AB  - 1. Sex differences in testosterone levels and sex-biased sensitivity to
      testosterone are the basis of some ideas postulated to account for sex-linked
      environmental vulnerability during early life. However, sex variation in
      circulating testosterone levels has been scarcely explored and never manipulated
      at post-natal stages of birds in the wild. 2. We measured and experimentally
      increased circulating testosterone levels in nestling Eurasian kestrels Falco
      tinnunculus. We investigated, possible sexual differences in testosterone levels
      and the effect of this hormone on growth (body mass and tarsus length) and cell
      mediated immunity in males and females. We also explored testosterone effects on
      rump coloration, a highly variable melanin-based trait in male nestlings. We
      analysed data on circulating testosterone levels of nestlings in 15 additional
      bird species. 3. Increased levels of testosterone tended to negatively affect
      body condition, reduced cell-mediated immune responses in male and female
      nestlings and also diminished the expression of grey rump coloration in male
      nestlings. No sex differences were observed in testosterone levels in either
      control or increased testosterone group nestlings, and no interactions were found
      between sex and treatment. However, male nestlings showed a lower cell-mediated
      immune response than females in both groups. 4. Our results indicate first, that
      a high level of testosterone in all nestlings in a brood entails costs, at least
      in terms of immunity, coloration and probably growth. Secondly, sex differences
      in post-natal cell-mediated immunity, and consequently in the capacity to prevent
      diseases, cannot be explained by sex differences in circulating testosterone
      levels. Finally, by comparing published data at an interspecific level,
      contradictory sex patterns in circulating testosterone levels have been found,
      supporting the idea that circulating testosterone might not be a proximate factor
      causing sex-dependent vulnerability in bird species.

PMID- 17184370
TI  - Systematic reviews of bladder training and voiding programmes in adults: a
      synopsis of findings on theory and methods using metastudy techniques.
AB  - AIM: This paper reports a comparison of four Cochrane systematic reviews on
      bladder training and voiding programmes for the management of urinary
      incontinence using metastudy descriptive techniques. It presents a synopsis of
      findings on theory and methods for interventions. BACKGROUND: From the mid-1970s
      bladder training, prompted voiding, habit retraining and timed voiding have been
      developed and form the basis of nursing practice for the management of urinary
      incontinence in adults in institutional and community settings. METHODS: A
      synopsis of four Cochrane systematic reviews was undertaken using metastudy
      techniques developed for qualitative research and has provided a discursive
      comparison and contrast of the selection and appraisal of primary research, meta
      theory and meta-method. FINDINGS: All programmes share a therapeutic focus on
      voiding and the degree and active participation of the client and caregiver.
      Bladder training focuses on the restoration of continence, while prompted
      voiding, habit retraining and timed voiding focus on the avoidance of
      incontinence. Bladder training and prompted voiding share the two characteristics
      of cognitive behavioural modification and active client participation. Habit
      retraining and timed voiding pre-empt episodes and avoid incontinence using
      operant conditioning rather than modifying behaviour. Variability of methods and
      operational terminology makes comparison between studies difficult. Use of
      cognitive behavioural approaches and operant conditioning need to be better
      understood in relation to future theory, interventions and study design. Bladder
      training is aimed at people who are cognitively and physically able, while the
      other voiding programmes are mainly used with for people with cognitive and
      physical impairments reliant on caregivers. CONCLUSION: The theoretical
      approaches underpinning bladder training and voiding programmes, their components
      and suitability for patients need to be re-considered when designing future
      studies. There is a need for long-term follow-up in future studies. Future trials
      should adhere to recognized standards of good practice and incorporate outcomes
      from existing systematic reviews to enable future meta-analysis to be undertaken.
      Metastudy techniques for the synthesis of qualitative research provide useful
      methods for the descriptive synopsis of quantitative systematic reviews.

PMID- 17184371
TI  - Systematic reviews of bladder training and voiding programmes in adults: a
      synopsis of findings from data analysis and outcomes using metastudy techniques.
AB  - AIM: This paper reports a comparison of the data analysis and outcomes from four
      Cochrane systematic reviews on bladder training and voiding programmes for the
      management of urinary incontinence using metastudy descriptive techniques to
      inform clinical practice, generate new ideas and identify future research
      directions. BACKGROUND: Bladder training is used for cognitively and physically
      able adults to regain continence by increasing the time interval between voids.
      Prompted voiding, habit retraining and timed voiding, collectively known as
      voiding programmes, are generally used for people with cognitive and physical
      impairments in institutional settings. Bladder training and voiding programmes
      feature as common clinical practice for the management of urinary incontinence.
      METHODS: A synopsis of four Cochrane systematic reviews that included randomized
      controlled trials on bladder training, prompted voiding, habit retraining and
      timed voiding was undertaken using metastudy techniques for the synthesis of
      qualitative research, and has provided a discursive comparison and contrast of
      the meta-data analysis and outcomes of these reviews. RESULTS: Frequency of
      incontinence was the most common and constant outcome measure of effectiveness in
      the reviews. Limited data were available on other health outcomes, change in
      dependency status, quality of life and cost-effectiveness. The systematic review
      on bladder training included different types of urinary incontinence, whereas
      those on voiding programmes did not differentiate the type of incontinence. There
      is evidence on the effectiveness of bladder training but long-term follow up
      studies are needed. Evidence on the effectiveness of voiding programmes is
      limited and not available for many outcomes. CONCLUSION: Future research needs to
      consider the theory underpinning interventions for bladder training and voiding
      programmes for urinary incontinence and should incorporate recognized 'quality'
      research designs, established outcomes and long-term follow up. It is unclear
      whether health outcomes for people with comorbidities, cognitive and physical
      impairments will improve if extensive diagnostic and assessment investigations
      are undertaken.

PMID- 17184372
TI  - Impact of hospital nursing care on 30-day mortality for acute medical patients.
AB  - AIM: This paper reports on structures and processes of hospital care influencing
      30-day mortality for acute medical patients. BACKGROUND: Wide variation in risk
      adjusted 30-day hospital mortality rates for acute medical patients indicates
      that hospital structures and processes of care affect patient death. Because
      nurses provide the majority of care to hospitalized patients, we propose that
      structures and processes of nursing care have an impact on patient death or
      survival. METHOD: A model hypothesizing the impact of nursing-related hospital
      care structures and processes on 30-day mortality was tested. Patient data from
      the Ontario, Canada Discharge Abstract Database 2002-2003, nurse data from the
      Ontario Nurse Survey 2003, and hospital staffing data from the Ontario Hospital
      Reporting System 2002-2003 files were used to develop indicators for variables
      hypothesized to impact 30-day mortality. Two multiple regression models were
      implemented to test the model. First, all variables were forced to enter the
      model simultaneously. Second, backward regression was implemented. FINDINGS:
      Using backward regression, 45% of variance in risk-adjusted 30-day mortality
      rates was explained by eight predictors. Lower 30-day mortality rates were
      associated with hospitals that had a higher percentage of Registered Nurse staff,
      a higher percentage of baccalaureate-prepared nurses, a lower dose or amount of
      all categories of nursing staff per weighted patient case, higher nurse-reported
      adequacy of staffing and resources, higher use of care maps or protocols to guide
      patient care, higher nurse-reported care quality, lower nurse-reported adequacy
      of manager ability and support, and higher nurse burnout. CONCLUSION: Just as
      hospitals and clinicians caring for patients focus carefully on completing
      accurate diagnosis and appropriate and effective interventions, so too should
      hospitals carefully plan and manage structures and processes of care such as the
      proportion of Registered Nurses in the staff mix, percentage of baccalaureate
      prepared nurses, and routine use of care maps to minimize unnecessary patient
      death.

PMID- 17184373
TI  - Organizational configuration of hospitals succeeding in attracting and retaining
      nurses.
AB  - AIM: This paper contrasts structural and managerial characteristics of low- and
      high-turnover hospitals, and describes the organizational configuration of
      attractive hospitals. BACKGROUND: In countries facing nurse shortages and
      turnover, some hospitals succeed in recruiting and retaining nurses. In Magnet
      Hospitals, managerial practices and environmental characteristics increase
      nurses' job satisfaction and their commitment to the organization, which in turn
      decreases nurse turnover. Such an approach suggests that organizations are best
      understood as clusters of interconnected structures and practices, i.e.
      organizational configurations rather than entities whose components can be
      understood in isolation. METHOD: From a sample of 12 hospitals whose nurse
      turnover was studied for 1 year, structural and organizational features of
      hospitals in the first and fourth quartiles, i.e. attractive (turnover <3.1%) vs.
      conventional (turnover >11.8%) were contrasted. A questionnaire, including
      perceptions of health-related factors, job demands, stressors, work schedules,
      organizational climate, and work adjustments antecedent to turnover, was received
      from 401 nurses working in attractive hospitals (response rate = 53.8%) and 774
      nurses in conventional hospitals (response rate = 54.5%). FINDINGS: Structural
      characteristics did not differentiate attractive and conventional hospitals, but
      employee perceptions towards the organization differed strikingly. Differences
      were observed for risk exposure, emotional demands, role ambiguity and conflicts,
      work-family conflicts, effort-reward imbalance and the meaning of work, all in
      favour of attractive hospitals (P < 0.001). Relationships with nursing
      management, work ability and satisfaction with working time, handover shifts and
      schedules were also better in attractive hospitals (P < 0.001). Job satisfaction
      and commitment were higher in attractive hospitals, whereas burnout and intention
      to leave were lower (P < 0.001). CONCLUSION: Organizational characteristics are
      key factors in nurse attraction and retention. Nurses face difficulties in their
      work situations, but some hospitals are perceived as healthy organizations. The
      concept of attractive institutions could serve as a catalyst for improvement in
      nurses' work environments in Europe.

PMID- 17184374
TI  - Effectiveness of turning with unequal time intervals on the incidence of pressure
      ulcer lesions.
AB  - AIM: This paper reports a study investigating whether repositioning patients
      lying on a pressure-reducing mattress alternately for 2 hours in a lateral
      position and 4 hours in a supine position reduces the incidence of pressure
      ulcers in comparison with repositioning every 4 hours. BACKGROUND: Repositioning
      is commonly recognized as an effective preventive measure. Almost no research has
      been carried out so far on the necessary turning frequencies to prevent pressure
      ulcer lesions. The pressure is higher in a lateral than in a supine position.
      METHOD: A two-arm randomized controlled trial was conducted in 16 Belgian elder
      care nursing homes. Patients with non-blanchable erythema were randomly assigned
      to either an experimental or a control group. In the experimental group (n =
      122), patients were repositioned alternately 2 hours in a lateral position and 4
      hours in a supine position. In the control group (n = 113), patients were
      repositioned every 4 hours. The sitting protocol was identical in both groups.
      Pressure areas were observed daily and classified according to the four grades of
      the European Pressure Ulcer Advisory Panel. RESULTS: In the experimental group,
      16.4% patients developed a pressure ulcer lesion (grade 2-4), while 21.2% did so
      in the control group. The incidence was not statistically significantly different
      between the two groups (P = 0.40). The severity (P = 0.65) and location (P =
      0.19) of pressure ulcer lesions, and the time to developing them (P = 0.29) were
      also similar in both groups. No patient developed a pressure ulcer at the hips. A
      considerable number of patients changed from a lateral to a supine position
      between the turning intervals. CONCLUSION: More frequent repositioning on a
      pressure-reducing mattress does not necessarily lead to fewer pressure ulcer
      lesions and consequently cannot be considered as a more effective preventive
      measure.

PMID- 17184375
TI  - Gender and the risk of falling: a sociological approach.
AB  - AIM: This paper reports a grounded theory study of the influence of gender on
      older people's perceptions of their risk of falling and their actions to prevent
      future falls. BACKGROUND: The incidence and rates of falls among older people,
      including injurious falls, are of much international concern. The risk of falling
      remains a major concern for older people since it increases with age, with those
      aged 85 years and over at greatest risk. However, research using a sociological
      approach to the topic is limited. METHODS: An exploratory design, with grounded
      theory analysis, was used. Data were collected during 2001 through in-depth
      interviews with a convenience sample of 40 older people living in south east of
      England. FINDINGS: Two core categories emerged: gendered meanings of risk and
      gendered responsibility. The social construction of the meaning of the risk of
      falling and of participants' actions was gendered. Older men and women had
      specific ways of talking about their 'risk' and identifying the risk factors for
      falling. Older men perceived themselves as 'responsible' and 'rational'
      individuals who expected to reduce their own risk of falling. Older women's
      expectations of themselves and of their peers explained their tendency to blame
      themselves or others for their falls. These perceptions influenced the actions
      they took to prevent future falls. CONCLUSION: Nurses and other healthcare
      professionals need to take account of the gendered meanings attached to falling
      by older men and women when carrying out risk assessments and giving advice on
      fall prevention.

PMID- 17184376
TI  - Assessing palliative care needs: views of patients, informal carers and
      healthcare professionals.
AB  - AIM: This paper reports a study to assess the palliative care needs of the adult
      population served by a healthcare provider organization in Northern Ireland from
      the perspectives of patients, informal carers and healthcare providers.
      BACKGROUND: Assessing palliative care need is a key factor for health service
      planning. Traditionally, palliative care has been associated with end-of-life
      care and cancer. More recently, the concept has been extended to include care for
      both cancer and non-cancer populations. Various approaches have been advocated
      for assessing need, including the exploration of professional provider and user
      perspectives of need. METHOD: Semi-structured qualitative interviews were
      undertaken with a purposive sample of patients and lay carers receiving
      palliative care services (n = 24). Focus groups were also conducted with multi
      professional palliative care providers (n = 52 participants) and face to face
      interviews were undertaken with key managerial stakeholders in the area (n = 7).
      The focus groups and interviews concentrated on assessment of palliative care
      need. All the interviews were transcribed verbatim and analysed using Burnard's
      framework. FINDINGS: Professional providers experienced difficulty in defining
      the term palliative care. Difficulties in communication and information exchange,
      and fragmented co-ordination between services were identified. The main areas of
      need identified by all participants were social and psychological support;
      financial concerns; and the need for choice and information. All participants
      considered that there was inequity between palliative care service provision for
      patients with cancer and non-cancer diseases. CONCLUSION: All patients,
      regardless of diagnosis, should be able to access palliative care appropriate to
      their individual needs. For this to happen in practice, an integrated approach to
      palliative care is essential. The study methodology confirms the value of
      developing a comprehensive approach to assessing palliative care need.

PMID- 17184377
TI  - 'Preparative waiting' and coping theory with patients going through gastric
      diagnosis.
AB  - AIM: This paper reports a study of how hospitalized patients with gastro
      intestinal problems going through diagnostic workups experience and handle the
      situation. It presents a theory of 'preparative waiting' and discusses it in
      relation to Lazarus' theory of appraisal, stress and coping. BACKGROUND: The pre
      diagnostic phase is reported to be the most stressful time of the illness for
      patients, but there is little research on this with patients in gastric units.
      According to Lazarus, appraisal and coping are concurrent, and stress must be
      understood as both an intra- and an inter-personal process. METHOD: A grounded
      theory design was chosen to conduct and analyse 18 in-depth interviews with 15
      patients in a gastric unit at a Norwegian university hospital. The data were
      collected in 2002-2003. FINDINGS: Participants' main concern was found to be how
      to prepare themselves for the results of the investigation and for life
      afterwards. The substantive grounded theory of 'Preparative waiting' presented
      here explains how they acted to do so. To be in the diagnostic phase meant to be
      in a process of continuously attempting to make sense of one's situation.
      Participants could judge their case to be harmful, a threat, a challenge, a
      benefit, or combinations of these. Their searches for realistic interpretation
      were balanced with searches for hopeful signs. This, together with lowering and
      rising of awareness, prevented them from despair. The process of understanding
      and handling the situation was concurrent, and was influenced by their
      relationships with family, friends, fellow patients, healthcare personnel and
      God. CONCLUSION: To the degree that patients trusted that nurses understood and
      were sensitive to the complex processes of appraising and coping, they became
      patients' key support persons. By providing adjusted information, coordinating
      care and examinations, respecting privacy, and inquiring about existential
      concerns, nurses could promote patients' ability to prepare for receiving the
      diagnosis and life after.

PMID- 17184378
TI  - Electronic searching to locate qualitative research: evaluation of three
      strategies.
AB  - AIM: This paper presents an evaluation of the effectiveness of three search
      strategies to identify research for a qualitative synthesis of patient
      experiences of living with a leg ulcer. BACKGROUND: Systematic reviews of
      research are increasingly the form of evidence used for evaluation of health
      care. There are well-established methods for conducting systematic reviews of
      effectiveness incorporating randomized controlled trials. Methods have been
      developed for the synthesis of qualitative research, but these are not widely
      used or evaluated. Searching for qualitative research is one of the least
      developed and tested areas in systematic reviewing of qualitative research.
      METHOD: The replication of three search strategies (free text, thesaurus and
      broad-based terms) developed for identification of qualitative research papers
      within electronic databases is described. Each strategy was run in seven
      electronic databases: MEDLINE, CINAHL, EMBASE, British Nursing Index, Social
      Science Citation Index, Applied Social Sciences Index and Abstracts, PsychInfo.
      The effectiveness of these strategies for identifying qualitative research for a
      synthesis of patients' experiences of living with a leg ulcer is discussed.
      FINDINGS: Each of the three search strategies produced similar numbers of
      potentially and actually relevant papers from each of the seven databases. These
      results were most striking for CINAHL, when all of the papers ultimately included
      in the review were identified by each search strategy. No other database
      identified all included papers. CONCLUSION: A simple search strategy using broad
      based terms was as effective as a complex one (free text) in locating qualitative
      research examining patients' experiences of living with a leg ulcer. For a
      question with a clear nursing focus, it may be sufficient to search only CINAHL
      in order to locate qualitative research. This result needs replicating with other
      nursing topics.

PMID- 17184379
TI  - Developing a mid-range theory of patient advocacy through concept analysis.
AB  - AIM: The aim of this paper is to clarify and refine the concept of patient
      advocacy through synthesizing the advocacy literature in nursing and to establish
      a theoretical basis for future studies on patient advocacy in nursing.
      BACKGROUND: Patient advocacy is an essential component of the Registered Nurse
      professional role. During the past 30 years, the patient advocacy role has become
      more important, but the concept of patient advocacy lacks a consistent definition
      and research into nurses' patient advocacy roles is limited. There have been few
      quantitative empirical studies on patient advocacy in nursing. METHOD: Walker and
      Avant's method of concept analysis was used as a guideline in examining the
      concept of patient advocacy through synthesizing the advocacy literature in
      English (1974-2006). FINDINGS: A mid-range theory of patient advocacy emerges
      during the process of synthesizing and analysing the advocacy literature. Three
      core attributes of the concept of patient advocacy are identified: (1)
      safeguarding patients' autonomy; (2) acting on behalf of patients; and (3)
      championing social justice in the provision of health care. They reflect nurses'
      patient advocacy roles at both macro- and micro-social levels. Antecedents of
      patient advocacy occur at both macro- and micro-social levels and call for
      nurses' advocacy roles in the healthcare system. Consequences produced by nurses'
      patient advocacy behaviours are contextual. Nurses' patient advocacy behaviours
      not only can positively influence the patients, other nurses and the nursing
      profession, but also can cause negative consequences for nurses who take action
      to advocate for patients. CONCLUSION: The proposed mid-range theory may be useful
      in guiding advocacy practice in nursing and in guiding research in the advocacy
      area. The proposed theory needs to be furthered refined and tested in the future.

PMID- 17184380
TI  - Re: treatment advice in primary care: a comparative study of nurse practitioners
      and general practitioners.

PMID- 17184384
TI  - IRIS from the inside.

PMID- 17184385
TI  - Why IRIS is outdated: an additional perspective.

PMID- 17184387
TI  - Comment on "Steady State Solutions to PBPK Models and Their Applications to Risk
      Assessment I: Route to Route Extrapolation of Volatile Chemicals," by Chiu and
      White in Risk Analysis, 26(3), 769-780.

PMID- 17184389
TI  - Poliomyelitis and the role of risk analysis in global infectious disease policy
      and management.

PMID- 17184390
TI  - Retrospective cost-effectiveness analyses for polio vaccination in the United
      States.
AB  - The history of polio vaccination in the United States spans 50 years and includes
      different phases of the disease, multiple vaccines, and a sustained significant
      commitment of resources. We estimated cost-effectiveness ratios and assessed the
      net benefits of polio vaccination applicable at various points in time from the
      societal perspective and we discounted these back to appropriate points in time.
      We reconstructed vaccine price data from available sources and used these to
      retrospectively estimate the total costs of the U.S. historical polio vaccination
      strategies (all costs reported in year 2002 dollars). We estimate that the United
      States invested approximately US dollars 35 billion (1955 net present value,
      discount rate of 3%) in polio vaccines between 1955 and 2005 and will invest
      approximately US dollars 1.4 billion (1955 net present value, or US dollars 6.3
      billion in 2006 net present value) between 2006 and 2015 assuming a policy of
      continued use of inactivated poliovirus vaccine (IPV) for routine vaccination.
      The historical and future investments translate into over 1.7 billion
      vaccinations that prevent approximately 1.1 million cases of paralytic polio and
      over 160,000 deaths (1955 net present values of approximately 480,000 cases and
      73,000 deaths). Due to treatment cost savings, the investment implies net
      benefits of approximately US dollars 180 billion (1955 net present value), even
      without incorporating the intangible costs of suffering and death and of averted
      fear. Retrospectively, the U.S. investment in polio vaccination represents a
      highly valuable, cost-saving public health program. Observed changes in the cost
      effectiveness ratio estimates over time suggest the need for living economic
      models for interventions that appropriately change with time. This article also
      demonstrates that estimates of cost-effectiveness ratios at any single time point
      may fail to adequately consider the context of the investment made to date and
      the importance of population and other dynamics, and shows the importance of
      dynamic modeling.

PMID- 17184391
TI  - Risk management in a polio-free world.
AB  - Inherent in the decision to launch the Global Polio Eradication Initiative in
      1988 was the expectation for many people that immunization against poliomyelitis
      would eventually simply stop, as had been the case with smallpox following its
      eradication in 1977. However, the strategies for managing the risks associated
      with a "polio-free" world must be continuously refined to reflect new
      developments, particularly in our understanding of the live polioviruses in the
      oral poliovirus vaccine (OPV) and in the international approach to managing
      potential biohazards. The most important of these developments has been the
      confirmation in 2000 that vaccine-derived polioviruses (VDPVs) can circulate and
      cause polio outbreaks, making the use of OPV after interruption of wild
      poliovirus transmission incompatible with a polio-free world. A comprehensive
      strategy has been developed to minimize the risks associated with eventual OPV
      cessation, centered on appropriate long-term biocontainment of poliovirus stocks
      (whether for vaccine production, diagnosis, or research), the controlled
      reintroduction of any live poliovirus vaccine (i.e., from an OPV stockpile), and
      appropriate use of the inactivated poliovirus vaccine (IPV). Although some
      aspects of this risk management strategy are still debated, there is wide
      agreement that no strategy would entirely eliminate the potential risks to a
      polio-free world. The current strategy for risk management in a polio-free world
      will continue to evolve with better characterization of these risks and the
      development of more effective approaches both to reduce those risks and to limit
      their consequences should they occur.

PMID- 17184392
TI  - Containment of polioviruses after eradication and OPV cessation: characterizing
      risks to improve management.
AB  - The goal of the World Health Organization is to stop routine use of oral
      poliovirus vaccine shortly after interruption of wild poliovirus transmission. A
      key component of this goal is to minimize the risk of reintroduction by
      destruction of polioviruses except in an absolute minimum number of facilities
      that serve essential functions and implement effective containment. Effective
      containment begins with a complete facility risk assessment. This article focuses
      on characterizing the risks of exposure to polioviruses from the essential
      vaccine production, quality control, and international reference and research
      facilities that remain. We consider the potential exposure pathways that might
      lead to a poliovirus reintroduction, including para-occupational exposures and
      releases to the environment, and review the literature to provide available
      estimates and a qualitative assessment of containment risks. Minimizing the risk
      of poliovirus transmission from a poliovirus facility to increasingly susceptible
      communities is a crucial and ongoing effort requiring understanding and actively
      managing the potential exposure pathways.

PMID- 17184393
TI  - Risks of paralytic disease due to wild or vaccine-derived poliovirus after
      eradication.
AB  - After the global eradication of wild polioviruses, the risk of paralytic
      poliomyelitis from polioviruses will still exist and require active management.
      Possible reintroductions of poliovirus that can spread rapidly in unprotected
      populations present challenges to policymakers. For example, at least one
      outbreak will likely occur due to circulation of a neurovirulent vaccine-derived
      poliovirus after discontinuation of oral poliovirus vaccine and also could
      possibly result from the escape of poliovirus from a laboratory or vaccine
      production facility or from an intentional act. In addition, continued
      vaccination with oral poliovirus vaccines would result in the continued
      occurrence of vaccine-associated paralytic poliomyelitis. The likelihood and
      impacts of reintroductions in the form of poliomyelitis outbreaks depend on the
      policy decisions and on the size and characteristics of the vulnerable
      population, which change over time. A plan for managing these risks must begin
      with an attempt to characterize and quantify them as a function of time. This
      article attempts to comprehensively characterize the risks, synthesize the
      existing data available for modeling them, and present quantitative risk
      estimates that can provide a starting point for informing policy decisions.

PMID- 17184394
TI  - The costs of future polio risk management policies.
AB  - Decisionmakers need information about the anticipated future costs of maintaining
      polio eradication as a function of the policy options under consideration. Given
      the large portfolio of options, we reviewed and synthesized the existing cost
      data relevant to current policies to provide context for future policies. We
      model the expected future costs of different strategies for continued
      vaccination, surveillance, and other costs that require significant potential
      resource commitments. We estimate the costs of different potential policy
      portfolios for low-, middle-, and high-income countries to demonstrate the
      variability in these costs. We estimate that a global transition from routine
      immunization with oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine
      (IPV) would increase the costs of managing polio globally, although routine IPV
      use remains less costly than routine OPV use with supplemental immunization
      activities. The costs of surveillance and a stockpile, while small compared to
      routine vaccination costs, represent important expenditures to ensure adequate
      response to potential outbreaks. The uncertainty and sensitivity analyses
      highlight important uncertainty in the aggregated costs and demonstrates that the
      discount rate and uncertainty in price and administration cost of IPV drives the
      expected incremental cost of routine IPV vs. OPV immunization.

PMID- 17184395
TI  - Perspective: determinants of the severity of poliovirus outbreaks in the post
      eradication era.
AB  - The potential consequences of the reintroduction of poliovirus in the post
      eradication era range from trivial (no or self-limited transmission and no
      clinical cases) to very serious (return of continued transmission of polioviruses
      and abandonment of the poliomyelitis eradication goal). This paper summarises the
      key determinants of such outcomes and identifies factors relating to infection
      surveillance, to vaccination policies at the time of OPV cessation and beyond,
      and to the still-unknown implications of these policies for infection
      transmission in environments with poor sanitation, as particularly important.
      Explicit consideration of these issues should encourage studies on the
      effectiveness of IPV vaccines in reducing poliovirus transmission in tropical
      environments, and should influence the location and containment requirements of
      facilities for vaccine production and storage, and for poliovirus-related
      research, in the era after cessation of OPV.

PMID- 17184396
TI  - Evaluation of response scenarios to potential polio outbreaks using mathematical
      models.
AB  - Appropriate response to polio outbreaks represents an important prerequisite for
      achieving and maintaining global polio eradication. We use an existing dynamic
      disease transmission model to evaluate the impact of different aspects of
      immunization campaigns in response to polio outbreaks occurring in previously
      polio-free areas. This analysis yields several important insights about response
      strategies. We find that delay in response represents a crucial risk factor for
      occurrence of large outbreaks and we characterize the tradeoffs associated with
      delaying the initial response to achieve better population coverage. We also
      demonstrate that controlling most potential outbreaks will likely require at
      least three immunization rounds, although the impact of the optimal interval
      between rounds varies. Finally, long after oral poliovirus vaccine cessation the
      choice of target age groups during a response represents an important
      consideration.

PMID- 17184397
TI  - Global surveillance and the value of information: the case of the global polio
      laboratory network.
AB  - Effective control and eradication of diseases requires reliable information from
      surveillance activities, including laboratories, which typically incur real
      financial costs. This article presents data from a survey we conducted to
      estimate the costs of the Global Polio Laboratory Network (GPLN), which currently
      supports aggressive global surveillance for acute flaccid paralysis (AFP) to
      detect circulating polioviruses. The Global Polio Eradication Initiative (GPEI)
      of the World Health Organization (WHO) provides resources for some of the
      laboratory network costs, but the total cost of the network remains relatively
      poorly characterized given the limited documentation of national contributions.
      We surveyed network laboratories to quantify AFP surveillance support costs and
      provide data for cost estimates of potential posteradication surveillance
      policies related to the laboratories. We estimate that the GPLN currently
      requires millions (US dollars 2002) in total support annually, and that half of
      the support for national and regional reference laboratories comes from external
      donors through the WHO or bilateral agreements and half from within nations that
      host those laboratories. The article also presents the framework for considering
      the value of information from this global surveillance network and suggests that
      the expected value of surveillance information from the GPLN currently exceeds
      its costs. We also provided important insights about how the value of information
      may change after successful eradication of wild polioviruses.

PMID- 17184398
TI  - Development and consideration of global policies for managing the future risks of
      poliovirus outbreaks: insights and lessons learned through modeling.
AB  - The success of the Global Polio Eradication Initiative promises to bring large
      benefits, including sustained improvements in quality of life (i.e., cases of
      paralytic disease and deaths avoided) and costs saved from cessation of
      vaccination. Obtaining and maintaining these benefits requires that policymakers
      manage the transition from the current massive use of oral poliovirus vaccine
      (OPV) to a world without OPV and free of the risks of potential future
      reintroductions of live polioviruses. This article describes the analytical
      journey that began in 2001 with a retrospective case study on polio risk
      management and led to development of dynamic integrated risk, economic, and
      decision analysis tools to inform global policies for managing the risks of
      polio. This analytical journey has provided several key insights and lessons
      learned that will be useful to future analysts involved in similar complex
      decision-making processes.

PMID- 17184399
TI  - Quantifying potential health impacts of cadmium in cigarettes on smoker risk of
      lung cancer: a portfolio-of-mechanisms approach.
AB  - This article introduces an approach to estimating the uncertain potential effects
      on lung cancer risk of removing a particular constituent, cadmium (Cd), from
      cigarette smoke, given the useful but incomplete scientific information available
      about its modes of action. The approach considers normal cell proliferation; DNA
      repair inhibition in normal cells affected by initiating events; proliferation,
      promotion, and progression of initiated cells; and death or sparing of initiated
      and malignant cells as they are further transformed to become fully tumorigenic.
      Rather than estimating unmeasured model parameters by curve fitting to
      epidemiological or animal experimental tumor data, we attempt rough estimates of
      parameters based on their biological interpretations and comparison to
      corresponding genetic polymorphism data. The resulting parameter estimates are
      admittedly uncertain and approximate, but they suggest a portfolio approach to
      estimating impacts of removing Cd that gives usefully robust conclusions. This
      approach views Cd as creating a portfolio of uncertain health impacts that can be
      expressed as biologically independent relative risk factors having clear
      mechanistic interpretations. Because Cd can act through many distinct biological
      mechanisms, it appears likely (subjective probability greater than 40%) that
      removing Cd from cigarette smoke would reduce smoker risks of lung cancer by at
      least 10%, although it is possible (consistent with what is known) that the true
      effect could be much larger or smaller. Conservative estimates and assumptions
      made in this calculation suggest that the true impact could be greater for some
      smokers. This conclusion appears to be robust to many scientific uncertainties
      about Cd and smoking effects.

PMID- 17184400
TI  - Testing for additivity at select mixture groups of interest based on statistical
      equivalence testing methods.
AB  - Several assumptions, defined and undefined, are used in the toxicity assessment
      of chemical mixtures. In scientific practice mixture components in the low-dose
      region, particularly subthreshold doses, are often assumed to behave additively
      (i.e., zero interaction) based on heuristic arguments. This assumption has
      important implications in the practice of risk assessment, but has not been
      experimentally tested. We have developed methodology to test for additivity in
      the sense of Berenbaum (Advances in Cancer Research, 1981), based on the
      statistical equivalence testing literature where the null hypothesis of
      interaction is rejected for the alternative hypothesis of additivity when data
      support the claim. The implication of this approach is that conclusions of
      additivity are made with a false positive rate controlled by the experimenter.
      The claim of additivity is based on prespecified additivity margins, which are
      chosen using expert biological judgment such that small deviations from
      additivity, which are not considered to be biologically important, are not
      statistically significant. This approach is in contrast to the usual hypothesis
      testing framework that assumes additivity in the null hypothesis and rejects when
      there is significant evidence of interaction. In this scenario, failure to reject
      may be due to lack of statistical power making the claim of additivity
      problematic. The proposed method is illustrated in a mixture of five
      organophosphorus pesticides that were experimentally evaluated alone and at
      relevant mixing ratios. Motor activity was assessed in adult male rats following
      acute exposure. Four low-dose mixture groups were evaluated. Evidence of
      additivity is found in three of the four low-dose mixture groups. The proposed
      method tests for additivity of the whole mixture and does not take into account
      subset interactions (e.g., synergistic, antagonistic) that may have occurred and
      cancelled each other out.

PMID- 17184401
TI  - Dose response for infectivity of several strains of Campylobacter jejuni in
      chickens.
AB  - Although some major risk studies have been done for Campylobacter jejuni, its
      dose response is not well characterized. Only a single human study is available,
      providing dose-response information for only a single isolate. As substantial
      heterogeneity in infectivity has been acknowledged for other pathogens, it
      remains unknown how well this single study represents the dose-response relation
      for this pathogen. As future human challenge studies with Campylobacter are
      unlikely, we have to find other means of studying its infectivity. Several dose
      response studies have been done using chickens as host organisms. These studies
      may be used to obtain quantitative information on the variation in infectivity
      among different isolates of this pathogen. A hierarchical Bayesian model is well
      suited to describe heterogeneity, and we demonstrate how the beta-Poisson model
      of microbial infection may be adapted to allow for within- and between-isolate
      variation. Isolates tested in chickens can be categorized into two distinct
      groups: lab-adapted and fresh isolates, and we show how the hierarchical dose
      response model can be used to quantitatively describe their differences. Fresh
      isolates show higher colonization potential and less within-isolate variation
      than lab isolates. The results indicate that Campylobacter jejuni is highly
      infectious in chickens. Different isolates show great variation in infectivity,
      especially between lab and fresh isolates, indicating that human clinical
      (volunteer) studies on infectivity must be interpreted cautiously.

PMID- 17184402
TI  - When does information about probability count in choices under risk?
AB  - The question addressed in the present research is whether in naturalistic risky
      decision environments people are sensitive to information about the probability
      parameter. In Study 1, we showed that in naturalistic scenarios participants
      generally revealed little interest in obtaining information about the outcomes
      and probabilities. Moreover, participants asked fewer questions about
      probabilities for scenarios containing moral considerations. In Study 2, it was
      shown that, when supplied with information on probabilities, people could be
      sensitive to this information. This sensitivity depends on two factors. People
      were less sensitive to probabilities in scenarios perceived as containing ethical
      considerations. People were also less sensitive to probabilities when they were
      faced with a single-choice situation than when they were faced with a series of
      lotteries with different probabilities. This can be accounted for in terms of the
      evaluability principle.

PMID- 17184403
TI  - Exposure and prioritization--human screening data and methods for high production
      volume chemicals in consumer products: amine oxides a case study.

PMID- 17184404
TI  - Risk-based objectives for the allocation of chemical, biological, and
      radiological air emissions sensors.
AB  - This article addresses the problem of allocating devices for localized hazard
      protection across a region. Each identical device provides only local protection,
      and the devices serve localities that are exposed to nonidentical intensities of
      hazard. A method for seeking the optimal allocation Policy Decisions is
      described, highlighting the potentially competing objectives of maximizing local
      risk reductions and coverage risk reductions. The metric for local risk
      reductions is the sum of the local economic risks avoided. The metric for
      coverage risk reductions is adapted from the p-median problem and equal to the
      sum of squares of the distances from all unserved localities to their closest
      associated served locality. Three graphical techniques for interpreting the
      Policy Decisions are presented. The three linked graphical techniques are applied
      serially. The first technique identifies Policy Decisions that are nearly Pareto
      optimal. The second identifies locations where sensor placements are most
      justified, based on a risk-cost-benefit analysis under uncertainty. The third
      displays the decision space for any particular policy decision. The method is
      illustrated in an application to chemical, biological, and/or radiological weapon
      sensor placement, but has implications for disaster preparedness, transportation
      safety, and other arenas of public safety.

PMID- 17184405
TI  - Predicting emergency evacuation and sheltering behavior: a structured analytical
      approach.
AB  - We offer a general approach to predicting public compliance with emergency
      recommendations. It begins with a formal risk assessment of an anticipated
      emergency, whose parameters include factors potentially affecting and affected by
      behavior, as identified by social science research. Standard procedures are used
      to elicit scientific experts' judgments regarding these behaviors and
      dependencies, in the context of an emergency scenario. Their judgments are used
      to refine the model and scenario, enabling local emergency coordinators to
      predict the behavior of citizens in their area. The approach is illustrated with
      a case study involving a radiological dispersion device (RDD) exploded in
      downtown Pittsburgh, PA. Both groups of experts (national and local) predicted
      approximately 80-90% compliance with an order to evacuate workplaces and 60-70%
      compliance with an order to shelter in place at home. They predicted 10% lower
      compliance for people asked to shelter at the office or to evacuate their homes.
      They predicted 10% lower compliance should the media be skeptical, rather than
      supportive. They also identified preparatory policies that could improve public
      compliance by 20-30%. We consider the implications of these results for improving
      emergency risk assessment models and for anticipating and improving preparedness
      for disasters, using Hurricane Katrina as a further case in point.

PMID- 17184406
TI  - Personal values, beliefs, and ecological risk perception.
AB  - A mail survey on ecological risk perception was administered in the summer of
      2002 to a randomized sample of the lay public and to selected risk professionals
      at the U.S. Environmental Protection Agency (US EPA). The ranking of 24
      ecological risk items, from global climate change to commercial fishing, reveals
      that the lay public is more concerned about low-probability, high-consequence
      risks whereas the risk professionals are more concerned about risks that pose
      long-term, ecosystem-level impacts. To test the explanatory power of the value
      belief-norm (VBN) theory for risk perception, respondents were questioned about
      their personal values, spiritual beliefs, and worldviews. The most consistent
      predictors of the risk rankings are belief in the new ecological paradigm (NEP)
      and Schwartz's altruism. The NEP and Schwartz's altruism explain from 19% to 46%
      of the variance in the risk rankings. Religious beliefs account for less than 6%
      of the variance and do not show a consistent pattern in predicting risk
      perception although religious fundamentalists are generally less concerned about
      the risk items. While not exerting as strong an impact, social-structural
      variables do have some influence on risk perception. Ethnicities show no effect
      on the risk scales but the more educated and financially well-off are less
      concerned about the risk items. Political leanings have no direct influence on
      risk rankings, but indirectly affect rankings through the NEP. These results
      reveal that the VBN theory is a plausible explanation for the differences
      measured in the respondents' perception of ecological risk.

PMID- 17184407
TI  - Exploring the structure of attitudes toward genetically modified food.
AB  - Although it is often thought that the British public is opposed to genetically
      modified (GM) food, recent qualitative work suggests that most people are
      ambivalent about GM food and crops. In this article we explore the structure of
      attitudes in order to examine whether attitudinal ambivalence can be captured by
      more quantitative methods. Based on the finding that the perceived risks and
      benefits of GM food can be treated as independent dimensions, we propose a four
      way typology of attitudes, consisting of a positive, negative, indifferent, and
      ambivalent group. This study showed that the differences between the four groups
      could best be described by three main dimensions: (1) a general evaluative
      dimension, (2) an involvement dimension, and (3) an attitudinal certainty
      dimension. While these different attitudinal dimensions have generally been
      studied in isolation, we argue that they should be studied collectively.

PMID- 17184408
TI  - A rational decision rule with extreme events.
AB  - Risks induced by extreme events are characterized by small or ambiguous
      probabilities, catastrophic losses, or windfall gains. Through a new functional,
      that mimics the restricted Bayes-Hurwicz criterion within the Choquet expected
      utility approach, it is possible to represent the decisionmaker behavior facing
      both risky (large and reliable probability) and extreme (small or ambiguous
      probability) events. A new formalization of the precautionary principle (PP) is
      shown and a new functional, which encompasses both extreme outcomes and
      expectation of all the possible results for every act, is claimed.

PMID- 17184411
TI  - Social science and bioethics: the way forward.
AB  - It is no surprise that bioethics and sociology developed an adversarial
      relationship: bioethicists value the clear descriptions of ethically charged
      situations provided by social scientists, but doubt the ability of those trained
      in social science to logically derive and discern 'the good'. For their part,
      social scientists - experts in observing and collecting data about the way the
      world is- find bioethicists ignorant of the ways elegantly crafted solutions to
      ethical problems get altered when incarnated in varied social and cultural
      settings. This discipline-centred self-affirmation can be a satisfying exercise,
      but it offers nothing to the project of promoting more moral medicine and health
      care. The articles collected in this volume demonstrate the value of
      collaboration between social scientists and bioethicists. Focusing on four themes
      found in recent sociological research in bioethics - ethics of research, the
      creation of moral boundaries, bioethics and social policy, and the bioethical
      imagination - this anthology offers practical models of co-operative work where
      the strengths of each discipline are brought together to advance our
      understanding of bioethical issues and to show the way toward just and effective
      social policy.

PMID- 17184412
TI  - Co-ordinating 'ethical' clinical trials: the role of research coordinators in the
      contract research industry.
AB  - Change in the way new drugs are developed, including the privatisation of
      clinical trials, has altered the arrangement and roles of healthcare professions.
      In this paper I examine one aspect of this change: the role of research
      coordinators in the conduct of contract research in the United States. My focus
      on coordinators highlights the ethical conflicts embedded in clinical trials. I
      describe the ways in which coordinators experience and contend with the conflict
      between research and care and show how their construction of ethics is distinct
      from institutional conceptions formally associated with human subjects research.
      My analysis demonstrates how the coordinators' focus on ethics is a response to
      their role conflict and an attempt to reinsert individualised care into the
      context of research.

PMID- 17184413
TI  - The many meanings of care in clinical research.
AB  - The conduct of clinical research often involves two distinguishable sets of
      relationships: the researcher-subject relationship, and the clinician-patient
      relationship. Some scholars argue that being a patient in a clinical care setting
      and a subject in a research study are so different that anything that would
      promote in subjects the view that they are in clinician-patient relationships is
      exploitative and deceptive. This paper presents findings intended to initiate a
      more empirically-based discussion of this issue. Using data from 82 in-depth
      interviews with physician-investigators, nurse-study coordinators and patient
      subjects in early phase clinical trials, we find that research personnel are
      likely to be seen, and to see themselves, as clinical caregivers. We also find
      evidence that while researchers and subjects often tend to view care and research
      as conflicting activities, both parties tend to see research as a way of caring
      for patients. We found no relationship, however, between subjects' perception of
      care-giving by researchers and the tendency to misunderstand that they are in a
      research study. Because research, by necessity and inclination, is unlikely ever
      to be 'care-free', we recommend that the ethical debate surrounding the danger of
      confusing research with treatment take into account the kinds of care described
      by respondents.

PMID- 17184414
TI  - The field worker's fields: ethics, ethnography and medical sociology.
AB  - Sociologists who do field work in medical settings face an intractable tension
      between their disciplinary field, which takes a critical perspective toward
      medicine, and their ethnographic field, which often includes physicians. This
      paper explores the ethical problems that result from the collision of the two
      fields. While in the field, ethnographers are forced to choose between sociology
      and their obligations to host members, as they decide whether to disclose their
      actual research agendas, whether to ask tough questions or to reveal their
      concerns, and whether to give advice. The tension persists when field workers
      leave the field to write, forcing them to choose between competing
      interpretations and to decide what to reveal or conceal in the interests of
      confidentiality. Through these moral choices about what to ask, record or present
      to the reader, ethnographers shape the academic field even as it shapes them.

PMID- 17184415
TI  - Ethical boundary-work in the embryonic stem cell laboratory.
AB  - Most accounts of the ethics of stem cell research are de- contextualised reviews
      of the ethical and legal literature. In this chapter we present a socially
      embedded account of some of the ethical implications of stem cell research, from
      the perspectives of scientists directly involved in this area. Based on an
      ethnography of two leading embryonic stem cell laboratories in the UK, our data
      form part of the findings from a larger project mapping the scientific, medical,
      social and ethical dimensions of innovative stem cell treatment, focusing on the
      areas of liver cell and pancreatic islet cell transplantation. We explore three
      key issues: what individual scientists themselves view as ethical sources of
      human embryos and stem cells; their perceptions of human embryos and stem cells;
      and how scientists perceive regulatory frameworks in stem cell research. We argue
      that these dimensions of laboratory practice are all examples of 'ethical
      boundary-work', which is becoming an integral part of the routine practice and
      performance of biomedical science. Our work adds to the relatively few
      sociological studies that explore ethics in clinical settings and to an even
      smaller body of work that explores scientists' views on the ethical issues
      relating to their research.

PMID- 17184416
TI  - Gift not commodity? Lay people deliberating social sex selection.
AB  - In this paper we explore lay people's discussions of the controversial topic of
      social sex selection (SSS). In the UK and many other countries, SSS is prohibited
      by law. In 2003 the UK Human Fertilisation and Embryology Authority, after an
      extensive public consultation, decided against changing the existing legislation.
      However, this initiative and similar consultation exercises have been criticised
      on the grounds that public opinion is poorly informed and reasoned. In our study,
      one of the most consistently expressed ideas was that children should be regarded
      as 'a gift' rather than 'a commodity'. In contrast, the 'gift not a commodity'
      argument is rarely cited positively in Anglo-American, secular-liberal bioethics.
      These metaphorical statements are condensed articulations of complex but coherent
      moral intuitions. Where much of the bioethics literature stresses parental
      autonomy, our lay discussants balanced this principle with ideas about the need
      to respect the personhood of the potential child, and the characteristics of a
      good parent. We conclude our analysis by considering the implications for
      expanding bioethics' knowledge base and improving the input of lay people in
      bioethical decision making.

PMID- 17184417
TI  - It's money that matters: the financial context of ethical decision-making in
      modern biomedicine.
AB  - While the importance of patient autonomy is widely acknowledged and discussed in
      the bioethics literature, clinicians' autonomy, their ability to make the best
      choices about patients' care free from outside interference, is far less debated.
      This paper takes one form of external influence over clinical decisions - the
      cost of drugs - and applies it to a specific case, that of HER2 positive breast
      cancer and the use of the drug Herceptin in the UK. Drawing on interviews with
      clinicians, researchers and policymakers, I explore the way financial decisions
      about Herceptin shape clinicians' autonomy, and how clinicians as individuals and
      as professional groups respond to these limits and seek to provide treatment to
      the highest number of the most deserving patients they can. The point of this
      paper is not to castigate bioethicists for misguidedly focusing on patient
      autonomy but point out that clinicians' autonomy may be so circumscribed by
      external factors that it may make no sense to speak of their actions as stemming
      from ethical decisions. At the same time, I suggest that financial constraints
      create areas at the margin of clinical practice which are deserving of bioethical
      consideration.

PMID- 17184418
TI  - The power of ethics: a case study from Sweden on the social life of moral
      concerns in policy processes.
AB  - In this paper I report on an ethnographic study of an ethics policy developed by
      a start-up genomics company at the time it gained all commercial rights to a
      population-based biobank in the town of Umea in northern Sweden. Tracing the
      interdependencies between power and morality, my research compares moral
      reflections and stances among 1) policymakers, 2) health professionals and 3)
      donors, in relation to the issues identified in the policy. These people seem to
      agree that trust and fairness are important issues and that 'something' needs
      protection in the face of commercial genetic research. However, their perceptions
      of trust, fairness and what it is that needs protection differ significantly. I
      conclude by considering the implications of variances in moral perspectives for
      the social study of ethics.

PMID- 17184419
TI  - Explaining the emergence of euthanasia law in the Netherlands: how the sociology
      of law can help the sociology of bioethics.
AB  - The debate over the legalisation of voluntary euthanasia is most often seen to be
      the result of three changes in society: individualisation, diminished taboos
      concerning death and changes in the balance of power in medicine. The fact that
      these changes occurred in many western countries but led to legalisation in only
      a few makes this claim problematic. I examine whether socio-legal propositions,
      with respect to the emergence of laws which focus on social control, offer a
      better approach to understanding the development of rules allowing and governing
      euthanasia. After a short sketch of the history of the Dutch law regulating
      euthanasia, I discuss these three societal changes in the light of shifts in the
      social control of medical behaviour that shortens life. I show that the Dutch
      relaxation of the prohibition of euthanasia goes together with new forms of
      social control: doctors' self control is complemented with second-party control
      (by patients), professional third-party control and governmental control. My work
      calls attention to the fact that bioethics is part of larger systems of social
      control.

PMID- 17184420
TI  - From biopolitics to bioethics: church, state, medicine and assisted reproductive
      technology in Ireland.
AB  - This paper examines the emerging bioethical debate on assisted reproductive
      technology (ART) in Ireland, which is shaped by the long-standing contentious
      issue of abortion and the constitutional protection afforded to the 'unborn'. The
      focus of the paper is on the way in which the terms of this debate are shaped and
      constrained by the historical relations of power between church, state and
      medicine. Since the representation of Ireland as a post-Catholic, plural republic
      is becoming increasingly mainstream to cultural and political discourse, we pay
      particular attention to how the Catholic Church embraces bioethics as a meta
      frame or code for refocusing questions of values, beliefs and meanings to sustain
      the ideal of Ireland as a 'pro-life' and essentially Catholic nation. The
      Catholic Church is not simply asserting its voice of dissent in the context of
      public debate as one voice amongst a plurality of other voices, but to shape the
      emerging debate as a powerful, institutional actor. The opportunity to do so is
      afforded by the lack of public debate on bioethical issues and the exceedingly
      slow pace at which bioethics is moving towards an institutionalised framework in
      Ireland. These events can be explained by the legacy of the social power of the
      Catholic Church in Ireland and the direct and indirect influence it has long
      exercised over public policy vis-a-vis the state and its institutions, including
      medicine. There are two interconnected threads to the contextual analysis
      presented in our case study: first, the legacy of the social power wielded by the
      Catholic Church, and its slow and incremental demise reflected in the pace of
      secularisation in Ireland and the privatisation of morality; second, the
      emergence of a bioethical regulatory debate on ART, which is mired in the
      abortion controversy. Our analysis focuses on a number of key contradictions and
      tensions in the way in which the key institutions of church, state and medicine
      navigate their own positions vis-a-vis a bioethics debate, and how this
      constrains public participation.

PMID- 17184421
TI  - Taking sociology seriously: a new approach to the bioethical problems of
      infectious disease.
AB  - After a history of neglect, bioethicists have recently turned their attention to
      the topic of infectious disease. In this paper we link bioethicists' earlier
      neglect of infectious disease to their under-appreciation of the extent to which
      the problem of infectious disease is related to social factors and thus to
      questions of justice. We argue that a social causation of illness model - well
      known to sociologists of medicine, but incompletely understood by bioethicists -
      will improve future bioethical analysis of issues related to infectious disease.
      By emphasising the relationships between social and economic structures of
      inequality and health, the social causation model provides a richer approach to
      ethical issues associated with infectious disease than the more commonly used
      biomedical model.

PMID- 17184422
TI  - Biobanks, bioethics and concepts of donated blood in the UK.
AB  - In recent years international bioethics bodies have made prominent declarations
      about the uses of donated tissue and related information in genetic research(1).
      Following the 'legislative' mode of bioethics(2), these organisations have put
      forward a number of general principles with a view to promoting the fair and
      equitable use of donated tissue in such research. However, government policies in
      this field are shaped differently in different national regimes. In this paper, I
      use recent debates in the UK about a national genetic 'biobank' to illustrate how
      the shape and texture of policy discussions surrounding the use of donated blood
      for genetic research have been built upon a prior national consensus that
      regarded blood as a public good.

PMID- 17184423
TI  - Embodiment and ethics: constructing medicine's two bodies.
AB  - The first 'modern' presentation of medical ethics is generally acknowledged to be
      Percival's text of 1803. The main theme of this influential pamphlet was the way
      in which medical practitioners should relate to one another. Two centuries later,
      clinical practice has very different moral underpinnings: bioethics, which first
      emerged in the middle of the 20(th) century, is not concerned with how doctors
      should interact with each other but with the responsibilities of medical
      practitioners to their patients. The shift from an ethics based on the
      relationship between practitioners to one based on the relationship with their
      patients is viewed as a major advance brought about by a more enlightened society
      engaging with the consequences of new technologies. But rather than addressing
      the changing picture of medical ethics in its own terms (which over the last few
      decades has been from the perspective of bioethics) I examine the history of
      medical ethics in its close relationship to the form and nature of the medical
      profession. Further, in a parallel thread I describe contemporary developments in
      public health and explore the similarities and connections between the two.

PMID- 17184424
TI  - Muscular dystrophy versus mitochondrial myopathy: the dilemma of the undiagnosed
      hypotonic child.

PMID- 17184425
TI  - Anesthesia and graft-vs-host disease after hematopoietic stem cell
      transplantation.

PMID- 17184426
TI  - Anesthesia-related morbidity and mortality after surgery for muscle biopsy in
      children with mitochondrial defects.
AB  - BACKGROUND: Children with mitochondrial defects (MD) may have an increased risk
      for cardiorespiratory and neurological complications from anesthesia. The aim of
      this study was to determine the incidence of perioperative complications and
      adverse events in children with MD. METHODS: We performed a retrospective review
      of the anesthesia, surgical and medical records of 155 children up to 10 years
      who underwent a diagnostic surgical muscle biopsy for suspected mitochondrial and
      muscle disorders between 1999 and 2003. The data of the 122 patients where a
      definite MD diagnosis was found were analyzed. Anesthesia was conducted according
      to the discretion of the attending staff. In children with MD the activity of the
      different complexes of the oxidative phosphorylation system was measured.
      RESULTS: From the preoperative assessment, signs of encephalopathy were most
      frequent (n = 93), followed by muscle weakness (n = 32), lactic acidosis (n =
      15), cardiomyopathy and/or conduction defects (n = 10) and chronic respiratory
      problems (n = 7). The mean age of the children with MD was 32.4 months (SD =
      26.9). The mean duration of anesthesia was 36.0 min (SD = 12.6) and the mean
      length of stay in the recovery room was 33.0 min (SD = 24.0). There were no major
      changes in heart rate or blood pressure which required pharmacological
      intervention during anesthesia or postanesthesia care unit (PACU) stay. A short
      episode of SpO2 <80% with airway obstruction occurred once in the PACU.
      Biochemical analysis in the children with a MD showed an isolated deficiency of
      one of the five protein complexes of oxidative phosphorylation in 42 children, a
      combination of complex deficiencies in 41 and no definite localization in 39
      children. CONCLUSION: With standard preoperative assessment, monitoring and
      anesthesia management, there were no major peroperative and postoperative
      anesthesia-related complications in children undergoing surgical muscle biopsy
      with a MD diagnosis.

PMID- 17184427
TI  - The risk of malignant hyperthermia in children undergoing muscle biopsy for
      suspected neuromuscular disorder.
AB  - BACKGROUND: It is assumed that those children with known or suspected
      neuromuscular disorders (NMD) are at increased risk for malignant hyperthermia
      (MH). Despite the lack of conclusive data, most of these children are managed
      with a nontriggering anesthetic. This study examined the risk of MH in children
      exposed to a triggering anesthetic while undergoing muscle biopsy for suspected
      NMD. METHODS: Between 1992 and 2005, the medical records of 351 children under 21
      years of age were identified as having undergone muscle biopsy for suspected NMD.
      Of these, only 274 received a volatile anesthetic agent or succinylcholine and
      were included for study. Records were examined for evidence of MH or
      rhabdomyolysis. RESULTS: No patient exhibited signs or symptoms suggestive of MH.
      One patient was found, by muscle biopsy, to have evidence of rhabdomyolysis prior
      to exposure to a volatile anesthetic. Of 274 patients, only three received
      succinylcholine. None developed MH or rhabdomyolysis. The estimated risk of a
      patient with suspected NMD developing MH as a result of exposure to volatile
      anesthetic agents during muscle biopsy is 1.09% or less. CONCLUSION: The
      estimated risk of MH or rhabdomyolysis is 1.09% or less in a diverse population
      of children with suspected NMD.

PMID- 17184428
TI  - Neonatal resuscitation courses for pediatric residents: comparison between
      Khartoum (Sudan) and Padova (Italy).
AB  - BACKGROUND: The efficacy of a Neonatal Resuscitation Program (NRP) has been
      previously evaluated in developed countries, but there is a lack of information
      regarding the impact of this teaching program in developing countries. Our aim
      was to compare the knowledge gained by University of Khartoum (Sudan) and
      University of Padova (Italy) pediatric residents following participation in the
      NRP course. METHODS: An 80-item questionnaire derived from the standard test
      contained in the American Heart Association and American Academy of Pediatrics
      Neonatal Resuscitation Manual was given to participants before and after the
      course. RESULTS: Twenty-five Sudanese and 26 Italian pediatric residents answered
      the pre- and postcourse questionnaire. The percentages of correct answers
      significantly improved from before to immediately after the course for both
      Sudanese (51.9 +/- 10.5% vs 84.9 +/- 5.8%; P < 0.01) and Italian (64.3 +/- 8.1%
      vs 94.0 +/- 3.9%; P < 0.01) pediatric residents. During the entire study, the
      scores obtained by Italian pediatric residents were higher than those reached by
      their Sudanese colleagues (P < 0.01). CONCLUSIONS: The trend of the knowledge
      attainment of both Sudanese and Italian pediatric residents was similar after NRP
      course participation. An NRP is effective in teaching neonatal resuscitation in
      developing countries.

PMID- 17184429
TI  - Hemodynamic differences between propofol-remifentanil and sevoflurane anesthesia
      for repair of cleft lip and palate in infants.
AB  - BACKGROUND: Propofol-remifentanil anesthesia is widely used in adults but few
      studies are available in infants. We aimed at comparing the hemodynamic effects
      of propofol-remifentanil vs sevoflurane-fentanyl anesthesia. In addition, we
      sought to investigate recovery and whether remifentanil induced acute opioid
      tolerance. METHODS: In total, 39 infants 4-6 months old were prospectively
      enrolled and randomized to receive either a combination of remifentanil and
      propofol (n = 17) or a sevoflurane-fentanyl anesthesia (n = 22) for surgical
      repair of cleft lip and palate. In both groups, sevoflurane was used for
      induction of anesthesia and fentanyl was administered before tracheal extubation.
      Mean arterial blood pressure and heart rate were recorded every 5 min after
      induction. We also recorded time from termination of surgery to tracheal
      extubation, postoperative behavior and the need for analgesia for the first 24 h
      after surgery. Postoperative observations were blinded. RESULTS: In the
      remifentanil-propofol group, the mean arterial blood pressure was higher [58 (51
      65) vs 51 (45-55), P = 0.02] and the mean heart rate was lower [111 (108-113) vs
      128 (122-143), P < 0.0001]. There were no differences in recovery time or
      behavior after surgery. In the remifentanil group, a median fentanyl dose of 4
      microg x kg(-1) was required to insure a smooth recovery, but there was no
      difference in morphine consumption during the first 24 h after surgery.
      CONCLUSIONS: A high-dose remifentanil-propofol infusion was associated with a
      higher blood pressure and lower heart rate than sevoflurane-fentanyl anesthesia
      in infants. Postoperative morphine consumption, recovery time and quality were
      similar.

PMID- 17184431
TI  - Ultrasound-guided umbilical nerve block in children: a brief description of a new
      approach.
AB  - BACKGROUND: The most popular peripheral nerve blocks used in umbilical hernia
      repair are rectus sheath block and paraumbilical block. However, multiple
      anatomic variations have been described and some complications may occur.
      Ultrasonographic guidance of peripheral nerve blocks has reduced the number of
      complications and improved the quality of blocks. This case series describes a
      new ultrasound-guided puncture technique of the 10th intercostal nerve in
      pediatric umbilical surgery. METHODS: Ten children (age range: 2-5 years)
      scheduled for umbilical hernia repair were included. Following the induction of
      general anesthesia, the ultrasonographic anatomy of the umbilical region was
      studied with a 10-MHz linear probe. An ultrasound-guided peripheral block of the
      10th intercostal nerve in the lateral edge of both rectus abdominis muscles (RMs)
      was performed (total of 20 punctures). Surgical conditions, intraoperative
      hemodynamic parameters, and postoperative analgesia by means of the modified
      CHEOPS scale were evaluated. RESULTS: Umbilical anatomy was clearly identified by
      ultrasound in all cases. The epigastric vessels were identified--above the
      umbilicus--within the depth of the muscular mass of the RM. The spread of local
      anesthetic was ultrasound-controlled in all cases. However, the intercostal nerve
      could not be visualized. All blocks were effective during the surgery.
      Postoperative analgesia was only required in two children in the second
      postoperative hour. There were no complications. CONCLUSIONS: Ultrasound guidance
      enables performance of an effective umbilical block in the lateral edge of RM.
      Further studies should be carried on to visualize the intercostal nerve and to
      compare this technique with the classical ones.

PMID- 17184430
TI  - Prevention of hypothermia in children under combined epidural and general
      anesthesia: a comparison between upper- and lower-body warming.
AB  - BACKGROUND: Children receiving combined epidural and general anesthesia may be at
      greater risk of hypothermia. Active warming should be undertaken to combat heat
      loss. With combined epidural and general anesthesia heat loss from the lower body
      may be greater than from the upper body because of shift of blood towards the
      vasodilated lower body. We assumed that application of the warming blanket to the
      lower body might provide better protection against hypothermia. To test this
      hypothesis, lower-body warming (LBW) was compared with upper-body warming (UBW)
      in a randomized comparative study. METHODS: Children subjected to open urologic
      surgery under combined epidural and general anesthesia were randomly allocated to
      either UBW n = 38 or LBW n = 35 using a forced-air warming blanket. Core and
      peripheral skin temperatures were monitored. Temperature gradients between
      forearm and fingertip during LBW and between leg and toe during UBW were
      calculated. The warmer was set at 32 degrees C, room temperature was around 22
      degrees C and fluids were infused at ambient room temperature. RESULTS: The
      changes in core temperature were comparable and parallel in both groups. Core
      temperature decreased significantly in each group at 1 h after induction compared
      with basal values. Temperature gradients at forearm-fingertip and at leg-toe were
      also comparable in both groups. Recovery was uneventful and no patient shivered
      in the recovery room. CONCLUSIONS: Lower body warming is as effective as UBW in
      prevention of hypothermia in children subjected to combined epidural and general
      anesthesia.

PMID- 17184432
TI  - Continuous SvO2 measurement in infants undergoing congenital heart surgery--first
      clinical experiences with a new fiberoptic probe.
AB  - BACKGROUND: SvO2-guided therapy, using fiberoptic oximetric catheters can help to
      improve the outcome after complex congenital heart surgery especially in infants
      undergoing the Stage 1-Norwood-Procedure. So far, fiberoptic catheters have to be
      placed transthoracically by the surgeon into the vena cava or the pulmonary
      artery putting the infant at an additional risk of bleeding at the time of
      catheter removal. METHODS: We used a new percutaneously applicable fiberoptic
      probe for continuous monitoring of central venous saturation in three infants
      undergoing modifications of the Stage 1-Norwood-Procedure (reconstruction of the
      aortic arch), two in combination with a bidirectional cavopulmonary connection
      (Glenn shunt), the third with reconstruction of the pulmonary arteries
      (biventricular repair). The approved clinical monitoring system consisted of a
      small (2 F) fiberoptic probe and a bed-side-monitor. The probe was inserted via
      the routine central venous access for such a case. RESULTS: Continuous SvO2
      measurement is feasible in infants using the CeVOX system in combination with
      routine central venous access, and the advantages of continuous monitoring are
      discussed. CONCLUSIONS: We believe that compared with transthoracically inserted
      oximetric catheter, the presented percutaneous technique avoids additional risks
      at the time of catheter removal (i.e. bleeding) and has become part of our
      standard management.

PMID- 17184434
TI  - Motion sickness as a predictor of postoperative vomiting in children aged 1-16
      years.
AB  - BACKGROUND: Motion sickness (MS) may be a risk factor for postoperative vomiting
      (POV), but its independent predictive value in children is not known. METHODS: A
      convenience sample of 70 consecutive patients aged 1-16 years scheduled for
      elective surgery were questioned, a history of MS was sought and patients were
      observed for the subsequent development of POV. RESULTS: The overall incidence of
      POV was 29%. Fourteen children (20%) had a history of MS; MS-positive children
      were more likely to vomit than those who were MS-negative (P < 0.01). The type of
      surgery, use of opioids or prophylactic antiemetics did not differ significantly
      between the groups. The sensitivity of MS as a predictor of POV is 45% and the
      specificity 90%, giving a positive predictive value of 64.3% and a negative
      predictive value of 80.4%. CONCLUSION: Motion sickness is associated with POV in
      this group of children, but its positive predictive value is fairly low.

PMID- 17184433
TI  - Isoflurane is associated with a similar incidence of emergence agitation/delirium
      as sevoflurane in young children--a randomized controlled study.
AB  - BACKGROUND: Children may be agitated or even delirious especially when recovering
      from general anesthesia using volatile anesthetics. Many trials have focused on
      the newer agents sevoflurane and desflurane but for the widely used isoflurane
      little is known about its potential to generate agitation. We investigated the
      emergence characteristics of small children after sevoflurane or isoflurane with
      caudal anesthesia for postoperative pain control. METHODS: After institutional
      approval and parental consent, anesthesia was randomly performed with sevoflurane
      (n = 30) or isoflurane (n = 29) in children at the age of 3.8 +/- 1.8 years
      during surgical interventions on the lower part of the body. After induction, all
      children received caudal anesthesia with bupivacaine (0.25%, 0.8 ml x kg(-1)).
      Postoperatively, the incidences of emergence agitation (EA) and emergence
      delirium (ED) were measured by a blinded observer using a ten point scale (TPS;
      EA = TPS > 5 ED = TPS > 7) as well as vigilance, nausea/vomiting and shivering.
      RESULTS: The two groups were comparable with respect to demographic data,
      duration of surgery and duration of anesthesia. There were also no differences in
      the period of time from the end of surgery until extubation, duration of stay in
      the PACU, postoperative vigilance and vegetative parameters. Incidence of EA was
      30% (9/30) for sevoflurane and 34% (10/29) for isoflurane during the first 60 min
      in the PACU (P = 0.785). Likewise, the incidence of ED was not different between
      the groups (20% and 24%, respectively). CONCLUSIONS: In our randomized controlled
      study, we found no difference in the incidence of EA or ED between sevoflurane
      and isoflurane. Therefore, the decision to use one or the other should not be
      based upon the incidence of EA or ED.

PMID- 17184435
TI  - Sedation for children with metachromatic leukodystrophy undergoing MRI.
AB  - BACKGROUND: Metachromatic leukodystrophy (MLD) is a lysosomal storage disease
      with infantile and juvenile onset with a poor prognosis and magnetic resonance
      imaging (MRI) plays a fundamental role in its diagnosis. Procedural sedation is
      needed to carry out MRI on children. Very few case reports have been published on
      anesthesia or sedation for MLD patients. METHODS: We prospectively studied 18 MLD
      patients undergoing sedation for brain MRI. Twenty consecutive similar-aged ASA I
      children undergoing MRI during the same time span for suspected seizures and
      exhibiting no MRI brain alteration healthy (HLT) patients were also studied for
      comparison. In patients up to 3 years of age (T_MLD and T_HLT groups), sedation
      was induced with thiopental 5 mg x kg(-1) i.v. and further 2.5 mg x kg(-1) i.v.
      rescue boluses were given if the sedation level was inadequate. In patients over
      3 years of age (P_MLD and P_HLT groups), sedation was induced with propofol 1-1.5
      mg x kg(-1) i.v. and maintained with 0.1-0.15 mg x kg(-1) x min(-1) continuous
      i.v. infusion, which was increased if the sedation level was inadequate. We
      recorded complications, if any, caused by sedation (hypoxia, vomiting,
      bradycardia, other major arrhythmias, convulsions, MRI artifact movements with
      increasing sedation, prolonged recovery). RESULTS: No sedation complications
      occurred. The mean dose of thiopental required to warrant patient immobility was
      0.227 +/- 0.053 mg x kg(-1) x min(-1) of procedure in T_MLD patients and 0.119 +/
      0.061 mg x kg(-1) x min(-1) of procedure in T_HLT patients (difference not
      significant). The mean dose of propofol required for immobility was 0.119 +/-
      0.054 mg x kg(-1) x min(-1) of procedure in T_MLD patients and 0.115 +/- 0.043 mg
      x kg(-1) x min(-1) of procedure in T_HLT patients (difference not significant).
      CONCLUSIONS: Our protocol for sedation in the MRI setting proved safe and
      effective in children with MLD, who do not require different doses of sedatives
      compared with healthy children.

PMID- 17184436
TI  - Intravenous paracetamol for postoperative analgesia in a 4-day-old term neonate.
AB  - There are only a few clinical reports on the use of intravenous (i.v.)
      paracetamol in term neonates. This case report illustrates that when routes for
      administration of analgesics are restricted to i.v. only and when opioids are not
      indicated then i.v. paracetamol may be used. In our 4-day-old term infant,
      despite i.v. paracetamol for 48 h, the trough level during therapy was almost
      undetectable indicating rapid clearance. Although i.v. paracetamol is not
      licensed in this age group, it can prove very helpful when the only route of
      administration is intravenous.

PMID- 17184437
TI  - Diminished Blalock-Taussig shunt flow detected by cerebral oximetry.
AB  - Near-infrared spectroscopy is a noninvasive optical technique used to monitor
      brain tissue oxygenation. Measurement of cerebral oxygenation is a more sensitive
      monitor of oxygen delivery to the brain than other available monitors. Prolonged
      cerebral desaturation is correlated with poor neurological outcomes. We report a
      case where the cerebral oximeter alerted us to diminished blood flow in a
      preexisting Blalock-Taussig (subclavian artery to pulmonary artery) shunt.

PMID- 17184438
TI  - Noninvasive ventilation in a child affected by achondroplasia respiratory
      difficulty syndrome.
AB  - Achondroplasia can result in respiratory difficulty in early infancy, from
      anatomical abnormalities such as mid-facial hypoplasia and/or adenotonsillar
      hypertrophy, leading to obstructive apnea, or to pathophysiological changes
      occurring in nasopharyngeal or glossal muscle tone, related to neurological
      abnormalities (foramen magnum and/or hypoglossal canal problems, hydrocephalus),
      leading to central apnea. More often, the two respiratory components (central and
      obstructive) are both evident in mixed apnea. Polysomnographic recording should
      be used during preoperative and postoperative assessment of achondroplastic
      children and in the subsequent follow-up to assess the adequacy of continuing
      home respiratory support, including supplemental oxygen, bilevel positive airway
      pressure, or assisted ventilation.

PMID- 17184439
TI  - Bradycardia with sevoflurane in siblings with Branchio-oto-renal syndrome.
AB  - Branchio-oto-renal syndrome (BOR, Melnick-Fraser syndrome, MIM#113650) refers to
      a rare autosomal dominant disorder characterized by branchial cysts or fistulas,
      hearing loss, external ear malformation, preauricular pits and renal
      abnormalities. The authors present three episodes of significant bradycardia in
      two siblings diagnosed with BOR syndrome during the sevoflurane general
      anesthesia. There is no published experience of anesthesia with this syndrome.
      Bradycardia occurred variously at induction, maintenance and immediately prior to
      emergence and required surgical stimulation, atropine, or epinephrine to treat.
      We seek to raise awareness of the potential for bradycardia during the procedures
      in patients with this syndrome requiring volatile anesthesia, especially
      sevoflurane.

PMID- 17184440
TI  - Tramadol infusion for the pain management in sickle cell disease: a case report.
AB  - We present the analgesic management of a 4-year-old child who suffered from
      severe abdominal and leg pain during his first vaso-occlusive crisis with sickle
      cell disease, diagnosed as beta/S disease when he was 1 year old. His mother and
      father were carriers of beta-thalassemia and hemoglobin S, respectively. He had
      an upper respiratory tract infection in which a vaso-occlusive crisis was
      precipitated. On admission to hospital, fever, severe abdominal and leg pain were
      noted. Hemoglobin was 4 g x dl(-1) with accompanying prominent reticulocytosis
      and acute spleen enlargement. These findings indicated a sequestration crisis as
      well as vaso-occlusive disease. He was transfused with packed red cells.
      Paracetamol (40-60 mg x kg(-1) x day(-1)) and ibuprofen (20 mg x kg(-1) x day(
      1)) were administered to relieve pain. The child experienced moderate to severe
      pain (Oucher score 60-80) despite nonopioid analgesics, so a tramadol infusion
      (0.25 mg x kg(-1) x h(-1)) was started. During the tramadol infusion no morphine
      was required, the intensity of pain gradually decreased (Oucher score 20) and the
      child was able to move his legs. At the end of 3 days splenomegaly regressed, no
      fever and pain were observed and the infusion was stopped. In conclusion,
      tramadol infusion i.v. (0.25 mg x kg(-1) x h(-1)) combined with nonopioids was
      effective to relieve moderate to severe pain due to vaso-occlusive crisis and can
      be recommended before using morphine in a pediatric sickle cell crisis.

PMID- 17184441
TI  - Local anesthetic infiltration of the wound for supplemental postoperative pain
      management in a pediatric liver transplant patient.

PMID- 17184442
TI  - Anesthetic management in a child with deletion 9p syndrome.

PMID- 17184443
TI  - A novel method of intubation in two children with Pierre Robin syndrome.

PMID- 17184444
TI  - Alagille syndrome and anesthesia management.

PMID- 17184445
TI  - Internal jugular venous line misplacement into the epidural space in a low
      birthweight premature child.

PMID- 17184446
TI  - Dystrophin deficiency, inhalational anesthetics, and rhabdomyolysis.

PMID- 17184448
TI  - Here we go again--two rare diseases--are they related?

PMID- 17184451
TI  - Regarding: muscular dystrophy and the safety of inhalational agents.

PMID- 17184452
TI  - Systematic reviews--triumph of form over substance?
AB  - Cochrane systematic reviews are conducted to identify level 1a evidence. So far
      the ENT group have published 24 reviews, while around 70 titles are in various
      stages of the review process. Only one review has been able to produce Ia
      evidence and the rest recommended further trials. The majority of
      otorhinolaryngology reviews are unable to identify level 1a evidence due to the
      paucity of high quality randomised control trials. This presents a challenge,
      therefore - to identify and discuss alternate methods of evidence gathering for
      future research?

PMID- 17184453
TI  - Cochrane reviews of surgical treatments.

PMID- 17184454
TI  - Endoscopic versus open surgical interventions for inverted nasal papilloma: a
      systematic review.
AB  - Inverted nasal papilloma is a unique neoplasm characterised by a tendency to
      recur following excision, an association with malignancy and an ability to
      destroy bone. The coexistence with nasal polyps (not always sent for histology),
      the lack of a universally accepted staging system and the fact that most data on
      Inverted papilloma come from tertiary centres (selected cases probably the most
      aggressive) account for the difficulty in determining its true incidence.
      Treatment is surgical. The gold standard approach was an open radical procedure.
      The introduction of endoscopic surgery for primary or recurrent lesions has shown
      potential advantages. Lack of complications of open surgery together with
      improved access to specific nasal areas suggests that the endoscopic techniques
      in experienced hands and for selected lesions may be a good alternative. The aim
      of this review was to assess the effectiveness of the endoscopic versus open
      techniques for management of inverted papilloma. There is not enough evidence in
      the literature to support one or the other treatment option for management of
      inverted papilloma. There is a trend though towards endoscopic approach. Ideal
      management should aim at complete removal of all diseased mucosa with creation of
      wide cavities and long term follow-up to detect subsequent recurrence or
      malignant transformation.

PMID- 17184455
TI  - Prospective randomised single-blind controlled trial of glacial acetic acid
      versus glacial acetic acid, neomycin sulphate and dexamethasone spray in otitis
      externa and infected mastoid cavities.
AB  - OBJECTIVES: The literature reports the merits of antibacterial, antibiotic and
      steroid agents in treating otological infections but no controlled clinical trial
      has directly compared 2% glacial acetic acid (EarCalm; Stafford-Miller Ltd,
      Brentford, UK) against 2% glacial acetic acid, 0.1% dexamethasone and 3250 U/ml
      of neomycin sulphate (Otomize; Stafford-Miller Ltd) in the treatment of otitis
      externa and infected mastoid cavities. DESIGN: Prospective, single-blind
      randomised controlled trial. SETTING: Outpatients, Derby Royal Infirmary, Derby,
      UK. PATIENTS: Emergency and GP referrals with acute otitis externa (n = 53) and
      infected mastoid cavities (n = 56). MAIN OUTCOME MEASURES: Otoscopy was performed
      at initial randomisation and then at 2 and 4 weeks, the ear assessed for active
      and inactive disease. RESULTS: Patients with active otitis externa, 71% (15/21)
      resolved with glacial acetic acid, dexamethasone and of neomycin sulphate after 2
      weeks, increasing to 86% (18/21) after 4 weeks treatment. Patients on glacial
      acetic acid had only 38% (12/32) resolution after 4 weeks (P < 0.0005). Two per
      cent glacial acetic acid, dexamethasone and neomycin sulphate resolved only 30%
      (8/27) of infected mastoid cavities compared to only 10% (3/29) on glacial acetic
      acid (P < 0.07). A further 2 weeks treatment this increased to 67%, (18/27) with
      glacial acetic acid, dexamethasone and neomycin sulphate and 48% (14/29) with
      glacial acetic acid. These results are not statistically significant. CONCLUSION:
      Glacial acetic acid, dexamethasone and neomycin sulphate is significantly more
      effective in treating otitis externa when compared with glacial acetic acid. This
      effect failed to be significant in the infected mastoid cavities group. We
      therefore recommend that in conjunction with aural toilet, antibiotic/steroid
      combination is more effective than an antibacterial agent for otitis externa.
      Larger numbers of infected mastoid cavities are required to be studied.

PMID- 17184456
TI  - Safe magnetic resonance scanning of patients with metallic middle ear implants.
AB  - OBJECTIVE: To determine the MR scanning risk to patients with otologic implants.
      DESIGN: We used a repeated-measures study with an additional control measure to
      assess two aspects of risk; (i) movement of the device in the magnetic field, and
      (ii) absorption of energy leading to local heating. We used an ex vivo test
      method that met with international standards. We measured the effects in a
      Philips Intera Achieva 3 Tesla (T) MR scanner using a Sense Head 8 channel RF
      coil. SETTING: University-based magnetic resonance research facility. MAIN
      OUTCOME MEASURES: Heating or displacement of the stapedectomy pistons. RESULTS:
      No evidence of displacement or heating was found. CONCLUSION: Complying with the
      ex vivo standard testing protocols, the Schuknecht and McGee wire pistons (device
      product numbers 140106 and 140108, respectively) were found to be safe in a 3 T
      MR scanner. These conclusions can be extrapolated to the in vivo case.

PMID- 17184457
TI  - Multidimensional assessment of female tracheoesophageal prosthetic speech.
AB  - OBJECTIVE: The objective of this study was to undertake a multidimensional
      assessment of female tracheoesophageal prosthetic speech. STUDY DESIGN: A cross
      sectional cohort study. SETTING: Head and Neck Unit in a tertiary oncology
      referral centre. PATIENTS: Ten female and 10 male total laryngectomy patients
      with no signs of recurrence and using voice prosthesis were compared to 10 normal
      female speakers. INTERVENTION(S): Electroglottographic and acoustic analysis of
      voice parameters for both sustained vowel /i/ and connected speech, perceptual
      evaluation using GRBAS (with 2 experienced raters) and questionnaire assessment
      using the University of Washington Quality of Life and the Voice Handicap Index.
      Statistical analysis was done using the Statistical Package for Social Sciences,
      (v. 14, SPSS Inc., Chicago III). RESULTS: Median age of the female larygectomy
      patients was 65 years (range: 41-81), that of male laryngectomees was 66.5 years
      (range: 40-79) and that of the normal female subjects was 47.5 years (range: 35
      72). All electroglottographic, acoustic parameters and GRBAS ratings of the
      female laryngectomy patients were significantly worse as compared with the normal
      female subjects. The median fundamental frequency (111.8 Hz) was comparable to
      male tracheoesophageal speakers (115.8 Hz). Mean composite University of
      Washington Quality of Life score and overall Voice Handicap Index score was
      79.3(12.5) and 47.5(27.6) for the female laryngectomy patients and for the males
      was 81.2 (9.6) and 39.4(18.7). CONCLUSIONS: Gender frequency differences as seen
      in normal subjects are lost following a laryngectomy operation as evidenced by
      electroglottographic and perceptual data. Although the quality of life scores are
      comparable to the male tracheoesophageal speakers, they exhibit a greater voice
      handicap as compared to their male counterparts.

PMID- 17184458
TI  - Can objective parameters derived from videofluoroscopic assessment of post
      laryngectomy valved speech replace current subjective measures? An e-tool-based
      analysis.
AB  - OBJECTIVES: The primary purpose of this study was to assess the
      pharyngoesophageal segment in total laryngectomy patients using a
      videofluoroscopy e-tool. STUDY DESIGN: Cross-sectional study. SETTING: Head and
      Neck Oncology Unit, Tertiary Referral Centre. PATIENTS: Forty-two patients
      following total laryngectomy. INTERVENTION: Videofluoroscopy using an e-tool
      (JRuler). MAIN OUTCOME MEASURES: Subjective and objective videofluoroscopy
      parameters correlated with the GRBAS scale and treatment variables. RESULTS: Of
      32 men and 10 women, mean age 63.5 years (10.8) the majority (64.3%) had a
      reasonable voice (good = 11 and poor = 4 patients). Comparing subjective and
      objective parameters, significant correlations were only seen with a smaller
      minimal neoglottic distance at phonation with no regurgitation of barium at
      phonation (P = 0.05) and a type 1 shape of neoglottis at phonation (P = 0.02).
      There were also significant correlations between smaller maximum sub-neoglottic
      distance at phonation and type 1 shape of neoglottis (P = 0.02), smaller maximum
      sub-neoglottic distance at rest and absence of stasis of barium at phonation (P =
      0.05) and the length of neoglottis at phonation and type 1 shape of neoglottis (P
      = 0.01). For perceptual evaluation, significant correlation was seen only between
      G1 voice and a smaller minimal neoglottic distance at phonation (P = 0.03)
      amongst the subjective and objective parameters. There were no correlations
      between visual parameters and the clinical parameters. CONCLUSIONS: Our
      observations suggest that this interesting concept has limitations. While
      objective and quantifiable data can be obtained using videofluoroscopy in
      laryngectomees, only a few correlate with each other and with voice quality.

PMID- 17184459
TI  - Questionnaire analysis of the swallowing-related outcomes following total
      laryngectomy.
AB  - OBJECTIVE: To determine the effects of a total laryngectomy on the swallow and
      subsequent quality of life in head and neck cancer patients. DESIGN: Cross
      sectional single centre cohort study. SETTING: Head and Neck Oncology Unit,
      Tertiary Referral Unit. PATIENTS: Sixty-two patients who underwent total
      laryngectomy at our centre participated in the study. METHODS: Subjects were
      stratified by age, sex, tumour stage, other procedures such as myotomy and nerve
      re-implantation. Pharyngectomy, glossectomy, flap reconstruction, neck dissection
      and previous radio- and chemotherapy were also assessed to see if they affected
      swallow and subsequent quality of life. Main outcome was measured using the MD
      Anderson Dysphagia Inventory questionnaire. RESULTS: Responses were received from
      46 males and 16 females (response rate of 80.5%) with a mean age of 64.7 years
      (SD 9.4). Median follow-up in patients was 90 months (range 1-276). The mean MD
      Anderson Dysphagia Inventory total score in our series of patients was 77.7 (SD
      16.6). MD Anderson Dysphagia Inventory global score was 79.4 (SD 22.6), Emotional
      score was 77.7 (SD 17.8), Functional score 81.3 (SD 15.9) and Physical score was
      74.1(SD 18). Statistically significant differences were seen between the
      emotional scores of glossectomised and non-glossectomised patients (Mann Whitney,
      P = 0.04). No significant correlation was seen between the subscale scores and
      the remaining treatment variables such as age, gender, site, tumour stage,
      myotomy, nerve implantation, radiotherapy, reconstruction and major
      complications. CONCLUSION: This questionnaire study is the largest of its type to
      assess the swallow of patients who have undergone laryngectomy at a single
      centre. The overall result confirmed that most patients had a subjectively good
      swallow. Only glossectomy and the method of PE segment closure were shown to
      significantly affect swallowing outcomes following surgery. We recommend further
      work especially prospective studies pre and post surgery using this or similarly
      validated instruments to fully assess swallow in the laryngectomy population.

PMID- 17184460
TI  - An anatomical comparison of Blair and facelift incisions for parotid surgery.
AB  - BACKGROUND: The rhytidectomy approach for parotidectomy allows the incision to be
      hidden, and post-operative scarring minimised. Furthermore, separate elevation of
      the Superficial Musculo-Aponeurotic System (SMAS) reduces the incidence of Frey's
      syndrome, and provides vascularized soft tissue for contour reconstruction. The
      technique has gained popularity particularly with plastic surgeons, but concerns
      persist that with this approach, particularly with lesions located anteriorly,
      access to the gland may be inadequate, and facial nerve identification may be
      compromised. MATERIALS AND METHODS: We undertook an anatomical study to
      quantitatively compare the surgical access achieved using the facelift approach
      with the conventional Blair incision, by comparing the distances between the
      parotid edge and the retracted flaps. RESULTS: Despite reduced tissue elasticity
      due to formaldehyde fixation, it proved possible to demonstrate all regions of
      the parotid gland to the operating surgeon with either approach. There were no
      significant differences in the distance between the parotid edge and the
      retracted skin flaps (P > 0.1; paired t-test). CONCLUSIONS: The facelift approach
      provides at least equal access to all regions of the parotid gland when compared
      to a Blair's incision. It is a superior approach aesthetically and its more
      widespread use in parotid surgery is advocated.

PMID- 17184461
TI  - Childhood otitis media with effusion.

PMID- 17184464
TI  - How we do it: A novel approach to the skin--abutment interface of the bone
      anchored hearing aid: use of local skin flaps.
AB  - Various techniques involving skin grafts have been described to obtain thin
      hairless immobile skin at the abutment interface of the bone-anchored hearing aid
      (BAHA), but none are without significant complications such as necrosis and/or
      infection leading to total graft failure. A novel technique involving four local
      thin skin flaps was developed to prevent serious complications. The procedure
      essentially involves raising skin flaps at the intradermal level leaving the hair
      follicles in the subcutaneous tissue, which is subsequently excised. We have used
      the skin-flap approach around 21 BAHAs on 19 patients (two patients had bilateral
      devices) and the only complications were minor skin loss immediately adjacent to
      the implants in two patients and mild skin infections, which settled with topical
      antibiotics, in three patients. The innovative technique described is simple and
      straightforward, and does not require any special instrumentation. Furthermore,
      it may have specific advantages, in terms of morbidity, over contemporary skin
      grafting methods primarily because of the retained intrinsic blood supply of the
      skin flaps.

PMID- 17184465
TI  - How we do it: diagrammatic recording of tympanomastoid procedures.
AB  - Accurate documentation of the operative findings of tympanomastoid procedures is
      essential for effective patient management and to satisfy the growing demands of
      clinical audit. Due to the three-dimensional complexity of the middle ear, it is
      difficult to represent graphically. Consequently, most surgeons only describe
      subjectively their operative, otological findings. We present for the first time
      a simple middle ear template which provides an objective tool to improve the
      recording of tympanomastoid procedures.

PMID- 17184466
TI  - How we do it: Switching from mechanical perforation to the CO2 laser; audit
      results of primary small-fenestra stapedotomy in a district general hospital.
AB  - The use of laser for stapedotomy was introduced in our department in the year
      2002, and since then has taken over the mechanical technique. A total of 85
      patients who had undergone primary stapedotomy with either technique are reported
      with regards to effectiveness and rate of side effects. Although footplate
      complications were reduced with the laser, short-term hearing outcomes were
      similar between the two techniques. In four occasions, the surgeon had to switch
      back to the mechanical technique unexpectedly. Stapedotomy will continue to be
      performed with the laser in our department, bearing in mind the occasional need
      for the older technique.

PMID- 17184467
TI  - How we do it: improving the success of endoscopic pharyngeal pouch stapling.
AB  - A simple technique to improve the success rate of endoscopic stapling
      diverticulotomy of pharyngeal pouches is described. Equipment used is readily
      available. This technique can be used in difficult cases when the pouch cannot be
      visualised using a Weerda diverticuloscope. It reduces the need for conversion to
      an open surgical procedure with associated increased risk of complications.

PMID- 17184468
TI  - How we do it: evaluation of nurse-led ENT services in the UK: a preliminary
      descriptive postal questionnaire survey.
AB  - There has been a steady growth in the volume and range of nurse led services in
      ENT practise in the UK. There was very little consistency in the titles of the
      nurses providing nurse led services but those nurses working in advanced practice
      roles now require courses, diplomas, degrees and study days related to ENT.
      Locally or nationally agreed practice guidelines can define nursing practice
      boundaries and ensure accountability. Monitoring and evaluation of nurse led
      services also requires attention.

PMID- 17184470
TI  - Intra-operative parathyroid hormone in secondary hyperparathyroidism: is it
      useful?

PMID- 17184471
TI  - Christmas survey: how polite are ENT surgeons?

PMID- 17184472
TI  - Consent issues with the National Prospective Tonsillectomy Audit: the Oxford
      experience.

PMID- 17184473
TI  - Short falls in epistaxis management. A nationwide survey in UK.

PMID- 17184474
TI  - A higher self-citing rate is not necessarily a bad thing: more correspondence
      equals more stimulation.

PMID- 17184475
TI  - Nasal septum loop technique for securing naso-gastric tube.

PMID- 17184476
TI  - The use of airway mannequins to improve the teaching of nasal packing.

PMID- 17184477
TI  - A safer method for inking the tattoo needle for pinnaplasty.

PMID- 17184478
TI  - How to avoid alar cartilage injury while securing post-nasal balloon packs.

PMID- 17184479
TI  - Use of systemic prophylactic antibiotics with anterior nasal packing in England,
      UK.

PMID- 17184480
TI  - Oestrogen, cognition and the maturing female brain.
AB  - Many women complain of memory and other cognitive difficulties at times that are
      associated with changes in ovarian steroid levels. However, the biological
      mechanisms through which ovarian steroids exert these effects remains poorly
      understood. Furthermore, the effect of hormone therapy, especially oestrogen
      therapy, on cognition and brain function in healthy women, and its role in the
      prevention of Alzheimer's disease, remains controversial. Here, we review the
      evidence that, in healthy women, ovarian steroids/oestrogen affects brain regions
      crucial to higher cognitive function at the macroscopic, microscopic, functional
      and neurotransmitter levels.

PMID- 17184481
TI  - Cardiovascular actions of orexin-A in the rat subfornical organ.
AB  - Orexin-A is a neuropeptide, primarily produced in the lateral
      hypothalamic/perifornical hypothalamus. Orexin receptors and immunoreactive
      neuronal fibres are widely distributed throughout the brain, suggesting
      integrative neurotransmitter roles in a variety of physiological systems.
      Intracerebroventricular injections of orexin-A increase blood pressure and
      stimulate drinking, and the subfornical organ (SFO), a circumventricular
      structure implicated in autonomic control, is a potential site at which orexin
      may act to exert these effects. We have therefore used microinjection techniques
      to examine the effects of orexin-A administered directly into the SFO on blood
      pressure and heart rate in urethane anaesthetised male Sprague-Dawley rats.
      Orexin-A microinjection (50 fmol) into the SFO caused site-specific decreases in
      blood pressure (SFO: mean area under curve (AUC) = -681.7 +/- 46.8 mmHg*s, n = 22
      versus non-SFO: 63.68 +/- 54.69 mmHg*s, n = 15, P < 0.001), and heart rate (SFO:
      mean AUC = -26.7 +/- 2.8 beats, n = 22, versus non-SFO: mean AUC = 1.62 +/- 2.1
      beats, n = 15, P < 0.001). Vagotomy did not alter the hypotensive or bradycardic
      responses elicited by orexin-A microinjection. Prior alpha-adrenoceptor blockade
      with phenoxybenzamine (1 mg/kg, i.v.) masked the orexin-A induced blood pressure
      (mean AUC = -122.6 +/- 17.6 mmHg*s, n = 4, P < 0.01 paired t-test) and heart rate
      (mean AUC = -6.7 +/- 1.7 beats, n = 4, P < 0.05, paired test) response. The
      orexin-A induced heart rate response was attenuated when beta-adrenoceptors were
      blocked with propranolol (1 mg/kg, i.v.; mean AUC = 0.6 +/- 2.8 beats, n = 5, P <
      0.01 paired t-test). These studies demonstrate that microinjection of orexin-A
      into the SFO causes site specific decreases in blood pressure and heart rate
      which is mediated by a reduction in sympathetic tone.

PMID- 17184483
TI  - Differential effects of centrally-administered oestrogen antagonist ICI-182,780
      on oestrogen-sensitive functions in the hypothalamus.
AB  - Oestrogen actions within the hypothalamus are essential for a range of
      reproductive functions. In this study, we sought to develop a method for
      suppressing central oestrogen action without affecting peripheral oestrogenic
      effects. We administered the oestrogen receptor antagonist ICI-182,780 (ICI) via
      crystalline implants into the left lateral ventricle or the arcuate nucleus and
      measured the effectiveness of this drug on three endpoints known to be regulated
      by oestrogen: gonadotrophin-releasing hormone (GnRH) pulse frequency,
      progesterone receptor expression and the generation of a sustained prolactin
      surge during late pregnancy. To confirm that central ICI administration had no
      effect on peripheral actions of oestrogen, we monitored changes in uterine
      weight. Intracerebroventricular ICI treatment reversed the inhibitory effects of
      oestrogen on GnRH pulse frequency, as measured by plasma luteinising hormone
      pulse frequency. No effect on the oestrogenic induction of progesterone receptors
      within the arcuate nucleus or ventromedial hypothalamus was observed; however, a
      small yet significant reduction in progesterone receptor expression within
      dopaminergic neurones in the arcuate nucleus was observed.
      Intracerebroventricular or direct crystalline ICI administration to the arcuate
      nucleus did not change the serum prolactin level during late pregnancy. Central
      administration of ICI did not affect uterine weight, and thus did not have a
      peripheral effect. These data suggest that central administration of ICI can
      overcome some actions of oestrogen in the brain, such as GnRH pulse frequency,
      but does not affect other oestrogen mediated actions, including the induction of
      progesterone receptors or the antepartum prolactin surge. Thus, it appears that
      there is a differential sensitivity to the inhibition of central oestrogen
      actions by ICI.

PMID- 17184482
TI  - Characterisation of the mouse vasoactive intestinal peptide receptor type 2 gene,
      Vipr2, and identification of a polymorphic LINE-1-like sequence that confers
      altered promoter activity.
AB  - The VPAC(2) receptor is a seven transmembrane spanning G protein-coupled receptor
      for two neuropeptides, vasoactive intestinal peptide (VIP) and pituitary
      adenylate cyclase-activating polypeptide (PACAP). It has a distinct tissue
      specific, developmental and inducible expression that underlies an important
      neuroendocrine role. Here, we report the characterisation of the gene that
      encodes the mouse VPAC(2) receptor (Vipr2), localisation of the transcriptional
      start site and functional analysis of the promoter region. The Vipr2 gene
      contains 12 introns within its protein-coding region and spans 68.6 kb.
      Comparison of the 5' untranslated region sequences for cloned 5'-RACE products
      amplified from different tissues showed they all were contained within the same
      exon, with the longest extending 111 bp upstream of the ATG start site.
      Functional analysis of the 3.2-kb 5'-flanking region using sequentially deleted
      sequences cloned into a luciferase gene reporter vector revealed that this region
      is active as a promoter in mouse AtT20 D16:16 and rat GH4C1 cell lines. The core
      promoter is located within a 180-bp GC-rich region proximal to the ATG start
      codon and contains potential binding sites for Sp1 and AP2, but no TATA-box.
      Further upstream, in two out of three mice strains examined, we have discovered a
      496-bp polymorphic DNA sequence that bears a significant identity to mouse LINE-1
      DNA. Comparison of the promoter activity between luciferase reporter gene
      constructs derived from the BALB/c (which contains this sequence) and C57BL/6J
      (which lacks this sequence) Vipr2 promoter regions has shown three-fold
      difference in luciferase gene activity when expressed in mouse AtT20 D16:16 and
      alphaT3-1 cells, but not when expressed in the rat GH4C1 cells or in COS 7 cells.
      Our results suggest that the mouse Vipr2 gene may be differentially active in
      different mouse strains, depending on the presence of this LINE-1-like sequence
      in the promoter region.

PMID- 17184484
TI  - G protein-coupled receptor 101 mRNA expression in the mouse brain: altered
      expression in the posterior hypothalamus and amygdala by energetic challenges.
AB  - GPCR101 is a recently identified orphan G protein-coupled receptor (GPCR)
      expressed abundantly in the human and mouse hypothalamus. In the absence of a
      ligand, a direct approach to determine the function(s) of this receptor is not
      possible. However, clues to the possible functions of GPCR101 may yield from
      information on the distribution of the receptor and the effect of in vivo
      manipulation upon the expression level of the receptor. In situ hybridisation on
      mouse brain sections revealed GPCR101 expression in a number of nuclei, including
      the amygdala, lateral parabrachial nucleus and nucleus of the solitary tract, as
      well as in the arcuate nucleus, posterior hypothalamus and paraventricular
      nucleus of the hypothalamus. Food-deprivation was found to increase GPCR101 mRNA
      level in the posterior hypothalamus and amygdala. In obese mice bearing the ob
      gene mutation, GPCR101 mRNA level decreased in the posterior hypothalamus and
      remained unaltered in the amygdala. By contrast, in both nuclei, GPCR101 mRNA
      level did not change significantly in obese ob/ob mice after intraperitoneal
      injection of leptin or in mice fed with a high fat diet. These data suggest that
      GPCR101 mRNA expression in the posterior hypothalamus and amygdala is regulated
      by a factor(s) other than leptin. Dual in situ hybridisation was used to
      establish the relationship between GPCR101 and neuropeptides expressed in the
      hypothalamus. In the arcuate nucleus, GPCR101 mRNA was expressed in approximately
      half of the population of neurones expressing the mRNA for the anorexigenic
      neuropeptide, pro-opiomelanocortin, which suggests a potential functional
      relationship.

PMID- 17184485
TI  - Transcriptional regulation of arylalkylamine-N-acetyltransferase-2 gene in the
      pineal gland of the gilthead seabream.
AB  - Pineal serotonin-N-acetyltransferase (arylalkylamine-N-acetyltransferase; AANAT)
      is considered the key enzyme in the generation of circulating melatonin rhythms;
      the rate of melatonin production is determined by AANAT activity. In all the
      examined species, AANAT activity is regulated at the post-translational level
      and, to a variable degree, also at the transcriptional level. Here, the
      transcriptional regulation of pineal aanat (aanat2) of the gilthead seabream
      (Sparus aurata) was investigated. Real-time polymerase chain reaction
      quantification of aanat2 mRNA levels in the pineal gland collected throughout the
      24-h cycle revealed a rhythmic expression pattern. In cultured pineal glands, the
      amplitude was reduced, but the daily rhythmic expression pattern was maintained
      under constant illumination, indicating a circadian clock-controlled regulation
      of seabream aanat2. DNA constructs were prepared in which green fluorescent
      protein was driven by the aanat2 promoters of seabream and Northern pike. In vivo
      transient expression analyses in zebrafish embryos indicated that these promoters
      contain the necessary elements to drive enhanced expression in the pineal gland.
      In the light-entrainable clock-containing PAC-2 zebrafish cell line, a stably
      transfected seabream aanat2 promoter-luciferase DNA construct exhibited a clock
      controlled circadian rhythm of luciferase activity, characteristic for an E-box
      driven expression. In NIH-3T3 cells, the seabream aanat2 promoter was activated
      by a synergistic action of BMAL/CLOCK and orthodenticle homeobox 5 (OTX5).
      Promoter sequence analyses revealed the presence of the photoreceptor conserved
      element and an extended E-box (i.e. the binding sites for BMAL/CLOCK and OTX5
      that have been previously associated with pineal-specific and rhythmic gene
      expression). These results suggest that seabream aanat2 is a clock-controlled
      gene that is regulated by conserved mechanisms.

PMID- 17184487
TI  - Programming of the appetite-regulating neural network: a link between maternal
      overnutrition and the programming of obesity?
AB  - The concept of a functional foetal "appetite regulatory neural network" is a new
      and potentially critical one. There is a growing body of evidence showing that
      the nutritional environment to which the foetus is exposed during prenatal and
      perinatal development has long-term consequences for the function of the appetite
      regulating neural network and therefore the way in which an individual regulates
      energy balance throughout later life. This is of particular importance in the
      context of evidence obtained from a wide range of epidemiological studies, which
      have shown that individuals exposed to an elevated nutrient supply before birth
      have an increased risk of becoming obese as children and adults. This review
      summarises the key pieces of experimental evidence, by our group and others, that
      have contributed to our current understanding of the programming of appetite, and
      highlights the important questions that are yet to be answered. It is clear that
      this area of research has the potential to generate, within the next few years,
      interventions that could begin to alleviate the adverse long-term consequences of
      being exposed to an elevated nutrient supply before birth.

PMID- 17184486
TI  - Effects of the short chain sugar acid 2-buten-4-olide on the hypothalamo
      pituitary-adrenal axis in normal and adjuvant-induced arthritic rats.
AB  - The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O),
      an endogenous sugar acid, on the hypothalamo-adenohypophysial system were
      examined in Lewis rats that were normal and in adjuvant-induced arthritic (AA)
      rats. In comparison with vehicle-treated rats, the plasma corticosterone and c
      fos mRNA levels in the paraventricular nucleus (PVN) of normal rats increased
      significantly after i.p. administration of 2-B4O. Dual immunostaining revealed
      that almost all corticotrophin-releasing factor (CRF)-immunopositive neurones in
      the parvocellular division of the PVN exhibited Fos-like immunoreactivity (LI)
      120 min after i.p. administration of 2-B4O (100 mg/kg). In the AA rats, repeated
      i.p. administration of 2-B4O (100 mg/kg) after immunisation significantly
      suppressed the expression of clinical symptoms and significantly increased plasma
      concentrations of corticosterone. Further, repeated i.p. administration of 2-B4O
      significantly increased CRF mRNA levels in the PVN and pro-opiomelanocortin mRNA
      levels in the anterior pituitary; however, they did not change arginine
      vasopressin mRNA levels in the parvocellular division of the PVN. These results
      suggest that i.p. administration of 2-B4O activates the hypothalamo-pituitary
      adrenal (HPA) axis via the activation of CRF neurones in the PVN, and the
      activation of the HPA axis by i.p. administration of 2-B4O may be associated with
      the inhibition of AA in rats.

PMID- 17184488
TI  - Foetal experience: lifelong consequences.
AB  - Modification of the foetal environment has lifelong consequences for endocrine
      function and behaviour. Maternal stress through activation of the hypothalamus
      pituitary-adrenal axis can lead to increased anxiety levels and stress reactivity
      in offspring. Furthermore, these effects can pass across generations. The race is
      now on to understand the mechanisms involved and to find ways to prevent or
      reverse the effects of an "adverse" early environment in human populations.

PMID- 17184489
TI  - Personal digital video: a method to monitor drug regimen adherence during human
      clinical investigations.
AB  - 1. Maintaining patient adherence to a drug regimen has proven to be difficult.
      Missed doses can impact drug efficacy and disease control, leading to increased
      health-care costs. 2. During clinical drug trials, poor adherence could lead to
      false conclusions regarding drug efficacy. Therefore, the purpose of the present
      study was to determine the feasibility of using personal digital video cameras to
      monitor adherence to a medication regimen during a clinical investigation. 3.
      Older men and women (60-78 years) participated in a double-blind, placebo
      controlled trial to determine the effect of ibuprofen or paracetamol on skeletal
      muscle adaptations to chronic resistance exercise training. Patients took three
      daily doses of either a placebo or the maximal daily over-the-counter dose of
      ibuprofen (1.2 g/day) or paracetamol (4.0 g/day) for 12 weeks. Prior to beginning
      the study, subjects were trained to use a personal digital video camera to record
      their drug consumption. 4. Subjects correctly recorded 4,956 of 5,375 doses,
      resulting in an average camera compliance rate of 92% (71-100%). 5. We describe a
      method of monitoring adherence to a prescribed drug regimen during a clinical
      investigation. Camera compliance rates, which directly confirm drug consumption,
      were higher than what is typically obtained with other methods of monitoring
      adherence. This camera compliance method provides the investigator with a simple
      and convenient means to generate direct evidence of drug consumption.

PMID- 17184490
TI  - Electrophysiological evidence for the interaction of substance P and glutamate on
      Adelta and C afferent fibre activity in rat hairy skin.
AB  - 1. The purpose of the present study was to investigate whether there was a
      cooperative interaction between substance P (SP) and glutamate (GLU) administered
      subcutaneously on Adelta and C primary afferent fibre activity in dorsal hairy
      skin of the rat in vivo. The single unit activities of Adelta and C afferent
      fibres were recorded by isolation of fibre filaments from the dorsal cutaneous
      nerve branches and the effects of subcutaneous injections of low doses of SP, GLU
      and SP + GLU on activity were determined. 2. Sub-threshold doses of SP (1 micro
      mol/L, 10 microL) administered subcutaneously into the dorsal hairy skin had no
      effect on the afferent discharges of either Adelta or C units. 3. The afferent
      discharges of 35% (11/31) of Adelta fibres and 33% (6/18) of C fibres were
      increased by local injection of the submaximal doses of GLU (10 micro mol/L, 10
      microL) into the receptive fields. 4. The GLU-induced excitatory response was
      significantly enhanced by coinjection of subthreshold doses of SP. The mean
      discharge rates of Adelta fibres and C fibres were increased from 5.84 +/- 1.54
      and 5.02 +/- 2.65 impulses/min to 19.91 +/- 4.35 and 17.58 +/- 5.59 impulses/min,
      respectively, whereas the excitatory proportions of Adelta and C fibres were
      increased from 35 and 33% to 84 and 83%, respectively. The duration of the
      excitation for Adelta fibres and C fibres was also significantly increased after
      coinjection of SP + GLU compared with that observed when either substance was
      given alone. 5. The present study provides electrophysiological evidence for an
      interaction between receptors for SP and GLU on the fine fibres activities in rat
      hairy skin, which may be involved in the mechanisms of hyperalgesia.

PMID- 17184491
TI  - Rosiglitazone modulates fasting and post-prandial paraoxonase 1 activity in type
      2 diabetic patients.
AB  - 1. In the present study, we have explored the effect of rosiglitazone on post
      prandial paraoxonase (PON)-1, an enzyme with potent anti-oxidant properties that
      may protect against atherosclerosis because increased post-prandial lipaemia,
      although sometimes understated, is part of the diabetic dyslipidaemia. 2. A
      randomized, cross-over, placebo-controlled, double-blind clinical trial was
      performed. Participants (19 type 2 diabetic patients on oral antihyperglycaemic
      agents) were randomly assigned to receive either placebo or rosiglitazone 4 mg
      twice daily for 8 weeks. After a 6 week wash-out, the alternative treatment was
      implemented. Standardized 6 h oral fat-loading tests were performed after each
      treatment period. 3. Patients assigned to rosiglitazone had increased fasting PON
      1 activity (from 331 +/- 29 to 362 +/- 32 U/L before treatment vs after
      treatment, respectively; P = 0.015), although the PON-1 mass did not change (68.8
      +/- 21.1 vs 64.2 +/- 25.4 mg/L before treatment vs after treatment,
      respectively). In addition, rosiglitazone significantly decreased fasting plasma
      peroxides compared with placebo (162 +/- 25 vs 214 +/- 28 mmol/L, respectively; P
      = 0.019). The post-prandial fall in PON-1 activity, expressed as area under the
      curve, was attenuated by rosiglitazone (-97 +/- 14 vs-161 +/- 24 Uh/L for
      rosiglitazone vs placebo, respectively; P = 0.02) and the increase in PON-1
      activity caused by rosiglitazone correlated with reductions in fasting plasma
      glucose (r = -0.42; P < 0.05), homeostatic model assessment index (r = -0.59; P <
      0.01) and peroxides (r = -0.40; P = 0.07). 4. The present data indicate that
      rosiglitazone may convey increased protection against the oxidative modification
      that represents increased post-prandial lipaemia.

PMID- 17184492
TI  - Differential roles of ryanodine- and thapsigargin-sensitive intracellular CA2+
      stores in excitation-contraction coupling in smooth muscle of guinea-pig taenia
      caeci.
AB  - 1. To explore roles of intracellular Ca(2+) stores in excitation-contraction
      coupling in smooth muscle, we examined the effects of ryanodine, a fixer of
      ryanodine receptor-Ca(2+) channels to an open state, and thapsigargin, a
      selective inhibitor of the Ca(2+) pump in the intracellular stores, on smooth
      muscle contraction in the presence and absence of extracellular Ca(2+) in guinea
      pig taenia caeci. 2. In Ca(2+) -free solution, contractions induced by 0.1 mmol/L
      carbachol and 0.1 mmol/L histamine were reduced to approximately 65% of control
      by either 1 micro mol/L thapsigargin or 10 micro mol/L ryanodine. In contrast,
      caffeine-induced contraction was reduced to approximately 40% of control by
      ryanodine, but was not affected by thapsigargin. 3. In the presence of
      extracellular Ca(2+), thapsigargin slowly induced a large and sustained
      contraction. In contrast, ryanodine did not induce an apparent contraction, but
      increased the sensitivity of contractile responses to receptor agonists
      (carbachol, AHR-602 and histamine) or depolarizing high K(+) with no changes in
      the maximal contraction. 4. These results suggest that there are pharmacological
      and physiological differences between ryanodine- and thapsigargin-sensitive
      intracellular Ca(2+) stores in excitation-contraction coupling in smooth muscle,
      which may be responsible for their differential effects on the Ca(2+) -influx
      pathway.

PMID- 17184493
TI  - Statins reduce macrophage inflammatory protein-1alpha expression in human
      activated monocytes.
AB  - 1. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)
      exhibit a wide variety of anti-atherogenic effects that may be independent of
      their property to lower plasma cholesterol. 2. In order to systematically
      investigate these effects at a cellular level, we investigated gene expression in
      phorbol myristate acetate (PMA)-activated and non-activated human THP-1 monocytes
      in response to statins using cDNA arrays. 3. Of 588 genes tested, 26 were
      differentially expressed in the presence of statins. A marked reduction was found
      for the chemokine macrophage inflammatory protein-1alpha (MIP-1alpha). The
      decrease in MIP-1alpha mRNA expression after incubation with statins was
      confirmed by quantitative reverse transcription-polymerase chain reaction in THP
      1 monocytes and human freshly isolated monocytes. Macrophage inflammatory protein
      1alpha protein in THP-1 monocytes was reduced from 377 to 299 and 305 pg/mL by
      0.1 micro mol/L simvastatin and 0.01 micro mol/L cerivastatin, respectively. The
      reduction in MIP-1alpha expression by statins was due, at least in part, to
      transcriptional inhibition of MIP-1alpha promoter activity. 4. The CC receptor
      ligand MIP-1alpha is a chemokine that has been implicated in atherosclerotic
      lesion formation. The present findings suggest that statin-mediated
      immunomodulation by inhibiting MIP-1alpha could contribute to the beneficial
      effects of statin therapy independent of lowering plasma cholesterol.

PMID- 17184494
TI  - Biochemical evaluation of antidiabetogenic properties of some commonly used
      Indian plants on streptozotocin-induced diabetes in experimental rats.
AB  - 1. Diabetes mellitus is a serious metabolic disorder with micro- and
      macrovascular complications that results in significant morbidity and mortality.
      2. The aim of the present study was to evaluate the hypoglycaemic efficacy of
      commonly used traditional Indian plants, such as Murraya koenigii, Mentha
      piperitae, Ocimum sanctum and Aegle marmelos, in streptozotocin (STZ)-induced
      experimental rats. 3. Oral administration of the ethanolic extract of these
      plants resulted in a significant decrease in the levels of blood glucose,
      glycosylated haemoglobin and urea, with a concomitant increase in glycogen,
      haemoglobin and protein, in diabetic rats. Treatment with these plant extracts
      also resulted in an increase in insulin and C-peptide levels and glucose
      tolerance. 4. The decreased activities of carbohydrate-metabolising enzymes, such
      as hexokinase, glucose-6-phosphate dehydrogenase and glycogen synthase, in
      diabetic rats were significantly elevated towards near normal in rats treated
      with extracts of M. koenigii, O. sanctum and A. marmelos; the increased
      activities of lactate dehydrogenase, fructose-1,6-bisphosphatase, glucose-6
      phosphatase and glycogen phosphorylase in STZ diabetic rats were significantly
      reduced following treatment with the plant extracts. 5. Elevated specific binding
      of [(125)I]-labelled insulin to the receptor found in diabetic rats was markedly
      decreased in extract-treated groups. However, treatment of diabetic rats with M.
      piperitae did not result in any significant modification in all parameters. 6.
      Phytochemical screening conducted by us revealed the presence of biologically
      active ingredients in the ethanolic extracts of M. koenigii, O. sanctum and A.
      marmelos, which may readily account for the observed hypoglycaemic activity.

PMID- 17184495
TI  - Essential oil of croton nepetaefolius and its main constituent, 1,8-cineole,
      block excitability of rat sciatic nerve in vitro.
AB  - 1. The effects of the essential oil of Croton nepetaefolius (EOCN) and its major
      constituent, 1,8-cineole, on the compound action potential (CAP) of nerve were
      investigated. 2. Experiments were performed in sciatic nerves dissected from
      Wistar rats, mounted in a moist chamber and stimulated at a frequency of 0.2 Hz,
      with electric pulses of 100 micros duration at 20-40 V. Evoked CAP were displayed
      on an oscilloscope and recorded on a computer. The CAP control parameters were as
      follows: peak-to-peak amplitude 8.1 +/- 0.6 mV (n = 15); conduction velocity 83.3
      +/- 4.2 m/s (n = 15); chronaxie 58.0 +/- 6.8 msec (n = 6); and rheobase 2.8 +/-
      0.1 V (n = 6). 3. Lower concentrations of EOCN (100 and 300 microg/mL) and 1,8
      cineole (153 and 307 microg/mL; i.e. 1 and 2 mmol/L, respectively) had no
      significant effects on CAP control parameters throughout the entire recording
      period. However, at the end of 180 min exposure of the nerve to the drug, peak-to
      peak amplitude was significantly (P < 0.05) reduced to 27.4 +/- 6.7 and 1.7 +/-
      0.8% of control values by 500 and 1000 microg/mL EOCN, respectively (n = 6), and
      to 76.5 +/- 4.4, 70.0 +/- 3.9 and 14.8 +/- 4.1% of control values by 614, 920 and
      1227 microg/mL (i.e. 4, 6 and 8 mmol/L) 1,8-cineole, respectively (n = 6).
      Regarding conduction velocity, at the end of the 180 min exposure period, this
      parameter was significantly reduced to 85.8 +/- 7.3 and 48.7 +/- 12.3% (n = 6) of
      control values by 500 and 1000 microg/mL EOCN, respectively, and to 86.4 +/- 4.5
      and 76.1 +/- 5.2% (n = 6) by 920 and 1227 microg/mL 1,8-cineole, respectively.
      Chronaxie and rheobase were significantly increased by the higher concentrations
      of both EOCN and 1,8-cineole. 4. It is concluded that EOCN and its main
      constituent 1,8-cineole block nerve excitability in a concentration-dependent
      manner, an effect that was totally reversible with 1,8-cineole but not with EOCN.
      This suggests that other constituents of EOCN, in addition to 1,8-cineole, may
      contribute to the mediation of this effect of EOCN.

PMID- 17184497
TI  - Tissue-specific regulation of insulin-like growth factors and insulin-like growth
      factor binding proteins in male diabetic rats in vivo and in vitro.
AB  - 1. Insulin-like growth factors (IGFs) are associated with the development of
      diabetes mellitus. The liver, kidney and heart have been implicated as important
      organs in the onset of diabetes mellitus. However, the effect of diabetes on the
      IGF system in these organs has not been fully described. Thus, we investigated
      changes in IGF-I, IGF-II and IGF binding proteins (IGFBPs) in male steptozotocin
      induced diabetic rats, as well as in a high glucose-induced in vitro model. 2.
      Serum levels of IGF-I were decreased, but the levels of IGF-II were increased, in
      diabetic rats compared with controls. The expression of IGFBP-3 in the serum was
      markedly decreased; in contrast, the expression of IGFBP-1 and -2 was increased
      in diabetic rats. The expression of IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and
      IGFBP-4 in the liver of the diabetic group was similar to that in the serum of
      diabetic rats. 3. In heart tissue of the diabetic group, IGF-I levels were
      decreased, but IGF-II levels were increased. In addition, the expression of IGFBP
      3, IGFBP-1 and IGFBP-2 was decreased in diabetic rats. 4. In the kidney of the
      diabetic group, IGF-I and IGF-II levels were increased. There was only slight
      expression of IGFBP-3 in the kidney and this was not altered in diabetic rats.
      Levels of IGFBP-1 and -2 were markedly increased in the kidney of diabetic rats.
      5. Insulin treatment recovered the changes in expression of IGF-I, IGF-II and
      IGFBPs in the serum, liver, heart and kidney. In the liver, heart and kidney, the
      expression of the insulin receptor was increased in male diabetic rats. 6. In
      conclusion, diabetes tissue-specifically alters the IGF system in the liver,
      heart and kidney in rats; this effect can be recovered by insulin treatment.

PMID- 17184496
TI  - Attenuation of ventricular hypertrophy and fibrosis in rats by pitavastatin:
      potential role of the RhoA-extracellular signal-regulated kinase-serum response
      factor signalling pathway.
AB  - 1. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins)
      manifest pleiotropic effects that may contribute to their therapeutic efficacy.
      However, the mechanism of the beneficial action of statins on cardiac hypertrophy
      and fibrosis remains unclear. We have now investigated this action of
      pitavastatin in Dahl salt-sensitive (DS) rats. 2. The DS rats progressively
      develop marked hypertension when fed a diet containing 8% NaCl from 7 weeks of
      age. These animals exhibited pronounced cardiac hypertrophy and fibrosis, as well
      as upregulation of fetal-type cardiac gene expression at 12 weeks of age,
      compared with DS rats fed a diet containing 0.3% NaCl. The abundance of mRNAs for
      collagen types I and III, angiotensin-converting enzyme, transforming growth
      factor-beta1 and connective tissue growth factor was also increased in the heart
      of rats on the high-salt diet. 3. Treatment of rats on the high-salt diet with a
      non-antihypertensive dose of pitavastatin (0.3 or 1 mg/kg per day) from 7 to 12
      weeks of age attenuated the development of cardiac hypertrophy and fibrosis, as
      well as inhibiting the upregulation of cardiac gene expression. Pitavastatin also
      blocked the translocation of RhoA to the membrane fraction of the left ventricle
      and RhoA activation, as well as the phosphorylation of the mitogen-activated
      protein kinases extracellular signal-regulated kinase (ERK)-1 and ERK-2 and an
      increase in the DNA binding activity of serum response factor (SRF) in the heart
      induced by the high-salt diet. 4. These findings suggest that the effects of
      pitavastatin on load-induced cardiac hypertrophy and fibrosis are independent of
      its cholesterol-lowering action and may be mediated, at least in part, through
      inhibition of RhoA-ERK-SRF signalling.

PMID- 17184498
TI  - Changes in the visceral functions of Plasmodium berghei-infected and -uninfected
      rats following administration of artemether.
AB  - 1. The effects of artemether (12.5, 25.0 and 50.0 mg/kg per day, i.m.),
      administered to different groups of Plasmodium berghei-infected and -uninfected
      adult Wistar rats for 1 week, were investigated. 2. The parameters evaluated were
      the feeding, drinking and urinating patterns of the rats and these were compared
      with those of rats that received normal saline. 3. Artemether caused a
      significant dose-dependent reduction in food consumption of both P. berghei
      infected and -uninfected rats (P < 0.05). Food intake in infected rats was
      reduced by approximately 7 g/24 h. This reduction in food intake was further
      reduced during drug treatment with artemether. Artermether also reduced food
      intake in uninfected rats. The food consumption of rats that received 12.5 and
      25.0 mg/kg artemether was restored after stopping treatment, in contrast with
      rats that received 50.0 mg/kg, in which the significant reduction in food
      consumption persisted 1 week after drug administration. 4. During treatment with
      artemether, the water intake of infected rats was significantly lower than that
      of uninfected rats in the 12.5 mg/kg artemether-treated group, but was
      significantly higher in infected rats than in uninfected rats dosed with 25.0 and
      50.0 mg/kg artemether. 5. For all doses of artemether tested, a significant
      increase in urine output was observed in infected rats during treatment and 1
      week after treatment, whereas in uninfected rats a significant increase in urine
      output was observed only following 25.0 and 50.0 mg/kg artemether 1 week after
      drug administration. 6. The present study confirms the anorexic activity of a
      high dose of artemether in both P. berghei-infected and -uninfected rats. It also
      indicates that high doses of the drug could cause impaired renal function in rats
      and that the significant increase in urine output could also be due to other
      effects of artemether, namely those on thirst, anti-diuretic hormone output and
      the osmotic pressure of the blood.

PMID- 17184499
TI  - Green tea extract impedes dyslipidaemia and development of cardiac dysfunction in
      streptozotocin-diabetic rats.
AB  - 1. The efficacy of green tea extract (GTE) on serum and cardiac lipids was
      investigated in streptozotocin (STZ)-diabetic rats. 2. Diabetes was induced in
      rats by a single intraperitoneal injection of STZ (60 mg/kg bodyweight). Six
      weeks after the induction of diabetes, GTE was administered orally for 4 weeks
      (300 mg/kg bodyweight daily). Bodyweight, heart weight, heart weight : bodyweight
      ratio, blood glucose, serum and cardiac lipids were determined in experimental
      rats. 3. In diabetic rats, there was a significant decrease in bodyweight with an
      increase in heart weight : bodyweight ratio and blood glucose. Diabetic rats had
      significantly increased serum levels of cholesterol, triglycerides, free fatty
      acids and low-density lipoprotein-cholesterol (LDL-C) and decreased levels of
      high-density lipoprotein-cholesterol (HDL-C). In the hearts of diabetic rats,
      there was a significant increase in cholesterol, triglycerides and free fatty
      acids levels, with an increase in lipoprotein lipase activity. 4. The
      administration of GTE to diabetic rats resulted in significant recovery in
      bodyweight, heart weight : bodyweight ratio and blood glucose levels. The
      administration of GTE reduced cholesterol, triglyceride, free fatty acid and LDL
      C levels, and increased HDL-C levels, in the serum of diabetic rats. In addition,
      GTE decreased cholesterol, triglyceride, free fatty acids levels and lipoprotein
      lipase activity in the myocardium of diabetic rats. These beneficial effects of
      GTE are ascribed to its antihyperglycaemic and hypolipidaemic activity. In
      conclusion, green tea can reduce the risk of cardiovascular disease in diabetes
      with a significant improvement in lipid metabolism.

PMID- 17184500
TI  - Characterization of the acute cardiovascular effects of intravenously
      administered insulin-like growth factor-I in conscious Sprague-Dawley rats.
AB  - 1. Insulin-like growth factor (IGF)-I has acute effects on cardiovascular
      function, including a well-characterized vasodilator response in isolated
      arteries. In addition to increasing the release of nitric oxide, IGF-I also has
      effects on a variety of other signalling pathways that affect vascular tone, in
      particular interactions with the sympathetic nervous system and the renin
      angiotensin-aldosterone system. We sought to characterize the effects of
      intravenous IGF-I on blood pressure and on responses to noradrenaline (NA),
      angiotensin II, acetylcholine and dobutamine. 2. Administration of IGF-I
      administration caused small decreases in mean arterial pressure (5.4 +/- 1.5%)
      and responsiveness to the prazosin-sensitive vasoconstrictor effects of NA (a 2.1
      +/- 0.6-fold increase in ED(50); n = 40; P < 0.01) and both effects were maximal
      at 200 microg/kg IGF-I. In addition, IGF-I significantly increased pulse pressure
      increases induced by low doses of dobutamine (from an increase in pulse pressure
      of 9.9 +/- 1.2 to 13.4 +/- 1.9 mmHg; n = 39; P < 0.05). Administration of IGF-I
      had no significant effect on responses to AngII or ACh. 3. Intravenous
      administration of IGF-I receptor antisense oligonucleotides (400 microg/kg)
      abolished the effects of IGF-I on NA-induced vasoconstriction (n = 11; P < 0.05),
      whereas administration of a mismatch oligonucleotide did not. 4. These data
      indicate that the maximal effects of exogenously administered IGF-I include
      modest direct vasodilation and inhibition of constrictor responses to NA and an
      increase in the effect of dobutamine on pulse pressure. The magnitude of these
      effects was less than what previous in vitro studies and those performed in
      anaesthetized animals may have indicated likely. 5. The modest magnitude of the
      dilator effects of IGF-I observed in conscious rats in vivo in the present study
      suggests that IGF-I is unlikely to be a major player in regulating vascular tone
      in normotensive animals.

PMID- 17184501
TI  - Expression of human factor IX gene in murine plasma through lentiviral vector
      infected haematopoietic stem cells.
AB  - 1. Haematopoietic stem cells (HSC) are an attractive target for gene therapy.
      Gene transfer to HSC can provide a potential cure for many inherited diseases.
      Moreover, recombinant lentiviral vectors can transfer genes efficiently to HSC.
      In the present study, we used the recombinant lentiviruses FUGW (Flip, ubiquitin
      promoter, GFP and WRE vector) and FUXW (Flip, ubiquitin promoter, F IX and WRE
      vector), which carry the enhanced green fluorescent protein (EGFP) and human
      factor IX (hFIX) gene, respectively, to infect HSC. 2. High titres of recombinant
      lentivirus were prepared from 293T cells by calcium phosphate-mediated transient
      cotransfection. Murine mononuclear cells (MNC) separated from murine bone marrow
      and HSC separated by magnetic cell sorting were cultured in vitro. Cells they
      were infected by the recombinant lentiviruses FUGW and FUXW. The expression of
      EGFP was observed under a fluorescent microscope and was analysed by fluorescence
      activated cell sorting, whereas the expression of hFIX was detected by ELISA. 3.
      The results show that the lentiviral vectors can efficiently infect murine HSC in
      vitro and that transduction was more efficient following cytokine treatment with
      interleukin (IL)-3, IL-6 and stem cell factor. 4. Haematopoietic stem cells
      infected with lentivirus FUXW were transplanted into [(60)Co]-irradiated non
      obese diabetic/severe combined immunodeficiency (NOD-SCID) mice. The expression
      of hFIX in the blood plasma of the transplanted mice reached a peak of 44.9 +/-
      7.6 ng/mL on Day 7. An assay of transaminase levels and a histological study of
      the liver showed that there was no significant damage following HSC
      transplantation to mice. 5. The results of the present study suggest that
      transplantation of HSC results in the persistant expression of hFIX in mice,
      which may be useful in haemophilia B gene therapy.

PMID- 17184502
TI  - Altered L-arginine/nitric oxide synthase/nitric oxide pathway in the vascular
      adventitia of rats with sepsis.
AB  - 1. In recent studies, the vascular adventitia has been established as an
      important source of inducible nitric oxide synthase (iNOS) and subsequent nitric
      oxide (NO) production, even more powerful than the media in response to certain
      inflammatory factors, such as lipopolysaccharide (LPS). The adventitia has an
      independent L-arginine (L-Arg)/NOS/NO pathway and is involved in the regulation
      of vascular function. In the present study, we explored the changes in and the
      pathophysiological significance of the L-Arg/NOS/NO pathway in the adventitia of
      rats with sepsis. 2. Sepsis was induced by caecal ligation and puncture in order
      to observe changes in L-Arg transport, NOS gene expression and activity and NO
      generation in the vascular adventitia to determine the mechanism of activation of
      the L-Arg/NOS/NO pathway. 3. Severe sepsis resulted in severe disturbance of
      haemodynamic features, with decreased mean arterial blood pressure, brachycardia
      and inhibited cardiac function (decreased left ventricular +/-dP/dt(max)). Left
      ventricular end-diastolic pressure was elevated threefold (P < 0.01) under
      anaesthesia. Rats with sepsis showed severe glucopenia and lacticaemia. Plasma
      levels of the inflammatory factors macrophage chemoattractant protein-1 and
      interleukin-8 were increased five- and 29-fold, respectively (P < 0.01). 4. In
      the adventitia of the thoracic and abdominal aortas, the L-Arg/NO pathway was
      similarly characterized: the uptake of [(3)H]-L-Arg was Na(+) independent, with
      the peak occurring at approximately 40 min incubation. Total NOS activity was
      largely calcium independent (> 90%). The V(max) of L-Arg transport in the sepsis
      group was increased by 83.5% (P < 0.01), but the K(m) value was not significantly
      different compared with controls. 5. The mRNA levels of cationic amino acid
      transporter (CAT)-1 and CAT-2B in the sepsis group were increased by 86 and 62%,
      respectively (both P < 0.01). Inducible NOS activity was increased 2.8-fold
      compared with controls (P < 0.01) and iNOS mRNA levels were elevated
      approximately sixfold (P < 0.01). The NO levels in the plasma and incubation
      media (incubation for 40 min) in the sepsis group were increased by 144 and 273%,
      respectively (both P < 0.01). 6. The Arg/NOS/NO pathway was activated in the
      vascular adventitia of rats with sepsis shock. The L-Arg/NOS/NO pathway in the
      aortic adventitia may play an important role in the pathogenesis of sepsis and
      septic shock.

PMID- 17184503
TI  - Regulation of hepatic cholesterol metabolism in CETP/LDLr mice by cholesterol
      feeding and by drugs (cholestyramine and lovastatin) that lower plasma
      cholesterol.
AB  - 1. The hepatic mechanisms involved in the simultaneous regulation of plasma
      cholesterol concentration and cholesteryl ester transfer protein (CETP) activity
      were investigated by sharply modifying the hepatic rates of cholesterol
      synthesis. This was accomplished by cholestyramine, lovastatin and cholesterol
      feeding in human CETP transgenic mice cross-bred with low-density lipoprotein
      receptor (LDLr)-knockout mice, generating CETP(+/-)/LDLr(+/-) mice, which present
      a plasma lipoprotein profile resembling that of humans. 2. Analyses of pooled
      data showed that the plasma CETP activity correlated positively with plasma total
      cholesterol concentration, hepatic CETP mRNA and the liver microsomal cholesterol
      content; a negative correlation was found between plasma CETP activity and the
      liver 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and LDLr mRNA
      levels. These coordinated events represent an efficient control system that
      stabilizes the cell cholesterol content. 3. Nonetheless, not all cholesterol
      metabolism regulatory systems seem to fit into a coherent pattern of responses,
      suggesting that other unknown cellular mechanisms play roles depending on the
      type of pharmacological intervention. 4. For example, microsomal cholesterol
      content was not affected by cholestyramine, but was increased on cholesterol
      feeding (as predicted), and, surprisingly, on lovastatin treatment. Furthermore,
      although both plasma cholesterol-lowering drugs increased CYP7A1 mRNA and had no
      effect on CYP27 mRNA, other metabolic components were differentially modified.
      Cholestyramine and lovastatin, respectively, did not modify and increased both
      HMG-CoA and sterol responsive element binding protein 1c mRNA, did not modify and
      lowered liver X receptor alpha mRNA, lowered and increased ATP binding cassette
      A1 mRNA and lowered and did not modify scavenger receptor B1 mRNA. 5. That is,
      different to unabsorbed cholestyramine, lovastatin, as an absorbed plasma
      cholesterol-lowering drug, may have modified the activity of other unknown genes
      that play roles in the interaction of CETP with the metabolism of hepatic
      cholesterol.

PMID- 17184504
TI  - Time-dependent transition from H(2)O(2)-extracellular signal-regulated kinase- to
      O(2)-nitric oxide-dependent mechanisms in the stimulatory effect of leptin on
      renal Na+/K+/-ATPase in the rat.
AB  - 1. Recent studies suggest that leptin, a peptide hormone secreted by white
      adipose tissue, is involved in the pathogenesis of arterial hypertension, in part
      by regulating renal sodium handling. Previously, we have demonstrated that in
      normal rats leptin has a time-dependent effect on renal Na(+)/K(+)-ATPase that
      drives tubular sodium reabsorption. Short-term leptin infusion results in a
      transient decrease in Na(+)/K(+)-ATPase activity, whereas prolonged
      administration stimulates the enzyme. 2. In the present study, we investigated
      whether these acute effects of leptin are preserved in rats with experimentally
      induced chronic hyperleptinaemia. 3. Hyperleptinaemia was induced by
      administration of exogenous leptin (0.25 mg/kg twice daily, s.c., for 7 days).
      Acute effects of leptin in anaesthetized control (normoleptinaemic) and
      hyperleptinaemic animals was investigated. Leptin was infused into the abdominal
      aorta proximally to the renal arteries for 0.5, 1, 2 or 3 h. 4. Leptin (1
      microg/min per kg) had a time-dependent effect on renal Na(+)/K(+)-ATPase in both
      the control and hyperleptinaemic groups. The inhibitory effect observed after 0.5
      h infusion was impaired in the hyperleptinaemic group. However, in both groups
      this effect was abolished by the Janus kinase inhibitor tyrphostin AG490 (100
      nmol/min per kg), as well as by the phosphatidylinositol 3-kinase inhibitors
      wortmannin (10 nmol/min per kg) and LY294002 (1 micromol/min per kg). 5. The
      stimulatory effect of leptin on Na(+)/K(+)-ATPase activity was observed after 3 h
      of infusion and was of similar magnitude in control and hyperleptinaemic groups.
      In the control group, the stimulatory effect of leptin was abolished by the NADPH
      oxidase inhibitor apocynin (1 micromol/min per kg), the H(2)O(2) scavenger
      catalase (1 mg/min per kg) and the extracellular signal-regulated kinase (ERK)
      inhibitor PD98059 (100 nmol/min per kg). In contrast, in the hyperleptinaemic
      group, the stimulatory effect of leptin was abolished by the cGMP analogue 8
      bromo-cGMP (100 nmol/min per kg) and by the superoxide dismutase mimetic tempol
      (100 micromol/min per kg) but was not affected by catalase or PD98059. 6. Leptin
      increased urinary H(2)O(2) excretion and ERK phosphorylation in the renal tissue
      only in the control group. 7. The results suggest that the acute stimulatory
      effect of leptin on renal Na(+)/K(+)-ATPase is mediated by divergent mechanisms
      depending on the chronic leptin level (i.e. by H(2)O(2)-dependent stimulation of
      ERK in normoleptinaemic animals and by superoxide-dependent impairment of the
      nitric oxide-cGMP pathway in hyperleptinaemic rats).

PMID- 17184505
TI  - Renal denervation attenuates long-term hypertensive effects of Angiotensin ii in
      the rat.
AB  - 1. It is well accepted that some of the long-term effects of angiotensin (Ang) II
      are mediated via the central nervous system. Some of these actions that are
      mediated by the circumventricular organs and the baroreceptor reflex are thought
      to then alter sympathetic nervous system activity. In particular, there is some
      debate as to the role of renal nerves in the chronic effects of AngII. The aim of
      the present study was to assess the contribution of the renal nerves in a long
      term model of progressive AngII-induced hypertension. 2. Male Sprague-Dawley rats
      were subjected to either bilateral renal denervation (RDX; n = 7) or sham surgery
      (SHAM; n = 8). Rats were instrumented with radiotelemetric transducers and venous
      catheters for the measurement of blood pressure and AngII infusion, respectively.
      A 4.0% NaCl diet and distilled water were provided ad libitum. The first 3 days
      served as the control period (7 mL/day, 0.9% NaCl, i.v.). This was followed by an
      infusion of AngII for 16 days (10 ng/kg per min, i.v.) and a 3 day recovery
      period identical to control. 3. Baseline arterial pressure between RDX and SHAM
      rats did not differ. Following AngII treatment, the arterial pressure of SHAM
      rats increased more rapidly than that of RDX rats. By Day 10 of treatment, the
      mean arterial pressure was significantly different between groups, having
      increased to 166 +/- 4 mmHg in SHAM rats and 135 +/- 11 mmHg in RDX rats. This
      trend continued for the remainder of AngII treatment. 4. The present results
      indicate that the renal nerves are necessary for the full expression of AngII
      induced hypertension.

PMID- 17184506
TI  - Protective effects of bendazac lysine on diabetic peripheral neuropathy in
      streptozotocin-induced diabetic rats.
AB  - 1. Diabetic neuropathy is a many faceted complication of both type I and II
      diabetes. The aim of the present study was to investigate the effects of bendazac
      lysine (BDL), an anticataract drug, on experimental diabetic peripheral
      neuropathy (DPN) in rats. 2. Diabetes was induced in rats by intraperitoneal
      injection of 75 mg/kg streptozotocin (STZ) dissolved in 0.1 mol/L citrate buffer
      (pH 4.4). Bendazac lysine was administered to rats at doses of 50, 100 and 200
      mg/kg twice a day for 12 weeks. 3. Diabetic rats without treatment showed
      hypopraxia, polydipsia, polyuria, slow weight gain, cataract, increased tail
      flick threshold temperature, decreased motor nerve conduction velocity (nd
      induced pathological morphological changes of myelinated nerve fibres. All these
      symptoms were ameliorated in diabetic rats treated with BDL. Bendazac lysine
      ameliorated the blood glucose concentration, glycosylated haemoglobin levels and
      insulin levels in the plasma of diabetic rats, reduced aldose reductase activity
      in erythrocytes and advanced glycation end-products in both nerves and serum and
      increase the activity of glutathione peroxidase in the nerves and Na(+)/K(+)
      ATPase in the nerves and erythrocytes. 4. Bendazac lysine exerts its protective
      effects against the progression of diabetic peripheral neuropathy in STZ-diabetic
      rats through multiple mechanisms and is a potential drug for the prevention of
      deterioration in DPN.

PMID- 17184507
TI  - Comparison between gastric scintigraphy and the [13C]-acetate breath test with
      Wagner-Nelson analysis in humans.
AB  - 1. The [(13)C]-acetate breath test (ABT) quantifies gastric emptying as the half
      [(13)CO(2)]-excretion time (T(1/2b)), but T(1/2b) differs from the scintigraphic
      half-emptying time (T(1/2s)). The aims of the present study were to accurately
      determine the half-emptying time by ABT with Wagner-Nelson analysis (T(1/2WN)),
      to compare T(1/2WN) with T(1/2s) and to validate the Wagner-Nelson strategy in
      ABT. 2. For a comparative study, eight volunteers simultaneously underwent ABT
      and scintigraphy. Anterior images were acquired and breath samples were collected
      every 15 min for 4.0 h after ingestion of a 200 kcal liquid meal labelled with 37
      MBq [(99m)Tc]-colloidal sulphur and 100 mg [(13)C]-acetate. For the validation
      experiment, another six volunteers underwent ABT, on two randomized occasions,
      using the 200 kcal liquid meal with 100 mg [(13)C]-acetate. On either of the two
      occasions, a gel-forming agent was stirred into the meal to intentionally delay
      gastric emptying by increasing meal viscosity. Breath samples were collected at
      regular 15 min intervals for 4 h post ingestion. 3. The Wagner-Nelson equation
      for ABT is F(t) = (A(breath)(t) + C(t)/0.65)/A(breath)(infinity), where F(t) is a
      fractional dose of the [(13)C] label emptied, C(t) is the [(13)CO(2)] excretion
      (% dose/h), A(breath)(t) is the area under the C(t) curve (% dose) and
      A(breath)(infinity) is the ultimate [(13)CO(2)] recovery in breath (% dose). The
      percentage gastric retention was estimated as 100 x (1 - F(t)). The time plots of
      scintigraphic activity and 100 x (1 - F(t)) were fitted to y(t) = 100 x e(-Kxt),
      K values were estimated mathematically for each plot by regression analysis and
      T(1/2s) and T(1/2WN) were calculated as (ln2)/K. The time versus pulmonary
      [(13)CO(2)] excretion plots were fitted to z(t) = m x k x beta x e(-kt)(1 - e(
      kxt))(beta-1), where m, k and beta are constants; T(1/2b) was calculated as 
      (ln(1 - 2(-1/beta))]/k. 4. Values of T(1/2WN) were closer to T(1/2s) than
      T(1/2b), although T(1/2WN) and T(1/2b) yielded significant under- and
      overestimation of T(1/2s), respectively. The high viscosity meal significantly
      prolonged T(1/2WN) and T(1/2b); T(1/2WN) could detect the delayed transit of the
      viscous meal more sensitively than T(1/2b). 5. The Wagner-Nelson method improves
      the accuracy of the ABT.

PMID- 17184510
TI  - Dual activation of cardiac sympathetic and parasympathetic components during
      conditioned fear to context in the rat.
AB  - 1. The present study investigates the contribution of the sympathetic and vagal
      parasympathetic systems to the tachycardic response of long-lasting (40 min)
      conditioned fear responses to context. 2. The conditioned fear response evoked by
      re-exposure to a footshock chamber was tested 10 min after intravenous injection
      of the beta-adrenoceptor antagonist propranolol (2 mg/kg) or the muscarinic
      antagonist atropine methyl nitrate (2 mg/kg) in rats implanted with
      radiotelemetric probes. 3. Compared with saline controls, the drugs did not
      change the behavioural component of the response (freezing, 22 kHz ultrasonic
      vocalizations) or its pressor component (+28 mmHg). 4. Propranolol abolished the
      tachycardic response of fear, whereas atropine more than doubled it (from +75 to
      +175 b.p.m. above resting baseline). 5. The results demonstrate that both
      sympathetic and vagal parasympathetic outflows to the heart are strongly
      activated during conditioned fear. The vagal activation may act to hold back
      cardiac acceleration while the animal waits for the aversive stimulus to come.

PMID- 17184509
TI  - Reflexly evoked coactivation of cardiac vagal and sympathetic motor outflows:
      observations and functional implications.
AB  - 1. The purpose of the present review is to highlight the pattern of activity in
      the parasympathetic and sympathetic nerves innervating the heart during their
      reflex activation. 2. We describe the well-known reciprocal control of cardiac
      vagal and sympathetic activity during the baroreceptor reflex, but point out that
      this appears to be the exception rather than the rule and that many other
      reflexes reviewed herein (e.g. peripheral chemoreceptor, nociceptor, diving
      response and oculocardiac) involve simultaneous coactivation of both autonomic
      limbs. 3. The heart rate response during simultaneous activation of cardiac
      autonomic outflows is unpredictable because it does not simply reflect the
      summation of opposing influences. Indeed, it can result in bradycardia
      (peripheral chemoreceptor, diving and corneal), tachycardia (nociceptor) and, in
      some circumstances, can predispose to malignant arrhythmias. 4. We propose that
      this cardiac autonomic coactivation may allow greater cardiac output during
      bradycardia (increased ventricular filling time and stronger contraction) than
      activation of the sympathetic limb alone. This may be important when pumping
      blood into a constricted vascular tree, such as is the case during the peripheral
      chemoreceptor reflex and the diving response.

PMID- 17184511
TI  - Differential control of cardiac functions by the brain.
AB  - 1. The idea is introduced that cardiac rate, contractility or atrioventricular (A
      V) conduction spread may be controlled independently by the brain. Limited data
      from reflex studies are cited to support this view. 2. Evidence is presented that
      individual autonomic post- and preganglionic neurons have quite specific actions
      on the heart. Premotor and other central neurons can have preferential actions on
      heart rate, contractility or A-V conduction. 3. The functional implications of
      selective cardiac control are discussed.

PMID- 17184512
TI  - 5-HT(1A) receptors in stress-induced cardiac changes: a possible link between
      mental and cardiac disorders.
AB  - 1. Mental disorders associated with chronic stressors are established risk
      factors for cardiac morbidity and mortality, but there is no satisfactory
      explanation of the mechanistic link between mental and cardiac disorders. 2. The
      present article presents the hypothesis suggesting that abnormal functioning of
      serotonin 5-HT(1A) receptors in the lower brain stem may represent this missing
      link. Currently available data suggest that there may be a global downregulation
      of 5-HT(1A) receptors in depressive and panic patients. 3. Recent animal results
      indicate that 5-HT(1A) receptors, located in the medullary raphe, possibly on the
      raphe-spinal presympathetic cardiomotor neurons, reduce stress-elicited
      activation of these neurons. 4. Decreased density/function of 5-H(1A) receptors
      in the raphe area (possibly occurring during chronic stress/depression) may lead
      to increased sympathetic outflow to the heart and, consequently, to the increase
      in noradrenalin release from the cardiac sympathetic nerve terminals.

PMID- 17184513
TI  - Differential control of cardiac and sympathetic vasomotor activity from the
      dorsomedial hypothalamus.
AB  - 1. The dorsomedial hypothalamus (DMH) plays a crucial role in mediating the
      cardiovascular responses to different stressors, including acute psychological
      stress and cold stress. Activation of neurons in the DMH evokes increases in
      arterial pressure and in the activity of sympathetic nerves innervating the
      heart, blood vessels and brown adipose tissue. The descending pathways from the
      DMH to the spinal sympathetic outflow include synapses with neurons in medullary
      nuclei and possibly other brain stem regions. 2. Recent studies from our and
      other laboratories have indicated that neurons in the rostral ventrolateral
      medulla (RVLM) and in the region of the raphe pallidus (RP) in the medulla are
      important components of the descending pathways that mediate the cardiovascular
      response to activation of the DMH. Neurons in the RP primarily mediate the
      sympathetic cardiac components of the DMH-evoked response, whereas the RVLM
      neurons primarily mediate the sympathetic vasomotor component. 3. Activation of
      DMH neurons not only increases heart rate and sympathetic vasomotor activity, but
      also resets the baroreceptor reflex such that it remains effective, without any
      decrease in sensitivity, over a higher operating range of arterial pressure. 4.
      Activation of 5-hydroxytryptamine 5-HT(1A) receptors in the medulla oblongata
      leads to a selective suppression of cardiac and sympathetic vasomotor components
      of the DMH-evoked response, but does not affect sympathetic reflex responses
      evoked from baroreceptors or chemoreceptors. Thus, central 5-HT(1A) receptors
      modulate cardiovascular responses evoked from the DMH in a highly potent but
      selective fashion.

PMID- 17184514
TI  - Mechanisms of sympathetic activation in heart failure.
AB  - 1. Heart Failure (HF) is a serious, debilitating condition with poor survival
      rates and an increasing level of prevalence. A characteristic of HF is a
      compensatory neurohumoral activation that increases with the severity of the
      condition. 2. The increase in sympathetic activity may be beneficial initially,
      providing inotropic support to the heart and peripheral vasoconstriction, but in
      the longer term it promotes disease progression and worsens prognosis. This is
      particularly true for the increase in cardiac sympathetic nerve activity, as
      shown by the strong inverse correlation between cardiac noradrenaline spillover
      and prognosis and by the beneficial effect of beta-adrenoceptor antagonists. 3.
      Possible causes for the raised level of sympathetic activity in HF include
      altered neural reflexes, such as those from baroreceptors and chemoreceptors,
      raised levels of hormones, such as angiotensin II, acting on circumventricular
      organs, and changes in central mechanisms that may amplify the responses to these
      inputs. 4. The control of sympathetic activity to different organs is regionally
      heterogeneous, as demonstrated by a lack of concordance in burst patterns,
      different responses to reflexes, opposite responses of cardiac and renal
      sympathetic nerves to central angiotensin and organ-specific increases in
      sympathetic activity in HF. These observations indicate that, in HF, it is
      essential to study the factors causing sympathetic activation in individual
      outflows, in particular those that powerfully, and perhaps preferentially,
      increase cardiac sympathetic nerve activity.

PMID- 17184515
TI  - Successful pulmonary administration of activated recombinant factor VII in
      diffuse alveolar hemorrhage.
AB  - INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a serious pulmonary
      complication seen in patients with autoimmune disorders and patients treated with
      chemotherapy or after hematopoietic stem cell transplantation. The clinical
      management of DAH is complex and the condition has a high mortality rate. Tissue
      factor is expressed in the lung alveoli during inflammation and therefore
      pulmonary administration of human recombinant activated factor VIIa (rFVIIa)
      could be a rational treatment option. METHODS: Six patients with acute,
      bronchoscopically confirmed DAH from a single intensive care unit university
      hospital center were included in the study of acute DAH in critically ill
      patients. The patients were treated with intrapulmonary administration of 50
      microg/kg rFVIIa in 50 ml of sodium chloride by bronchoalveolar lavage (BAL) with
      25 ml in each of the main bronchi, which was repeated after 24 hours in case of
      treatment failure. RESULTS: An excellent response, defined as complete and
      sustained hemostasis after a single dose of rFVIIa, was seen in three patients. A
      good response, meaning that sustained hemostasis was achieved by a repeated
      rFVIIa administration, was seen in the remaining three patients. In one of these
      patients, the BAL treatment was repeated twice; in another patient, the second
      dose of rFVIIa was administered by nebulizer after extubation after the initial
      BAL. The hemostatic effect was statistically significant (p = 0.031). The
      oxygenation capacity, as reflected by the PaO2/FiO2 (arterial oxygen
      pressure/inspiratory fractional oxygen content) ratio, increased significantly (p
      = 0.024) in all six patients following the local rFVIIa therapy. CONCLUSION:
      Symptomatic therapy of DAH after intrapulmonary administration of one or more
      doses of rFVIIa was found to have a good to excellent hemostatic effect in six
      consecutive patients with DAH. The intrapulmonary administration of rFVIIa seemed
      to have a high benefit-to-risk ratio. Larger series should confirm the safety of
      this approach.

PMID- 17184516
TI  - Recombinant activated factor VII as an adjunctive therapy for bleeding control in
      severe trauma patients with coagulopathy: subgroup analysis from two randomized
      trials.
AB  - INTRODUCTION: We conducted a post-hoc analysis on the effect of recombinant
      factor VIIa (rFVIIa) on coagulopathic patients from two randomized, placebo
      controlled, double-blind trials of rFVIIa as an adjunctive therapy for bleeding
      in patients with severe trauma. METHODS: Blunt and penetrating trauma patients
      were randomly assigned to rFVIIa (200 + 100 + 100 microg/kg) at 0, 1, and 3 hours
      after transfusion of 8 units of red blood cells (RBCs) or to placebo. Subjects
      were monitored for 48 hours post-dosing and followed for 30 days. Coagulopathy
      was retrospectively defined as transfusion of fresh frozen plasma (FFP) (>1 unit
      of FFP per 4 units of RBCs), FFP in addition to whole blood, and transfusion of
      platelets and/or cryoprecipitate. RESULTS: Sixty rFVIIa-treated and 76 placebo
      subjects were retrospectively identified as being coagulopathic. No significant
      differences were noted in baseline characteristics. The rFVIIa-treated
      coagulopathic subgroup consumed significantly less blood product: RBC transfusion
      decreased by 2.6 units for the whole study population (P = 0.02) and by 3.5 units
      among patients surviving more than 48 hours (P < 0.001). Transfusion of FFP
      (1,400 versus 660 ml, P < 0.01), platelet (300 versus 100 ml, P = 0.01), and
      massive transfusions (29% versus 6%, P < 0.01) also dropped significantly. rFVIIa
      reduced multi-organ failure and/or acute respiratory distress syndrome in the
      coagulopathic patients (3% versus 20%, P = 0.004), whereas thromboembolic events
      were equally present in both groups (3% versus 4%, P = 1.00). CONCLUSION:
      Coagulopathic trauma patients appear to derive particular benefit from early
      adjunctive rFVIIa therapy.

PMID- 17184517
TI  - Community hospitals--the place of local service provision in a modernising NHS:
      an integrative thematic literature review.
AB  - BACKGROUND: Recent developments within the United Kingdom's (UK) health care
      system have re-awakened interest in community hospitals (CHs) and their role in
      the provision of health care. This integrative literature review sought to
      identify and assess the current evidence base for CHs. METHODS: A range of
      electronic reference databases were searched from January 1984 to either December
      2004 or February 2005: Medline, Embase, Web of Knowledge, BNI, CINAHL, HMIC,
      ASSIA, PsychInfo, SIGLE, Dissertation Abstracts, Cochrane Library, Kings Fund
      website, using both keywords and text words. Thematic analysis identified
      recurrent themes across the literature; narrative analyses were written for each
      theme, identifying unifying concepts and discrepant issues. RESULTS: The search
      strategy identified over 16,000 international references. We included papers of
      any study design focussing on hospitals in which care was led principally by
      general practitioners or nurses. Papers from developing countries were excluded.
      A review of titles revealed 641 potentially relevant references; abstract
      appraisal identified 161 references for review. During data extraction, a further
      48 papers were excluded, leaving 113 papers in the final review. The most common
      methodological approaches were cross-sectional/descriptive studies, commentaries
      and expert opinion. There were few experimental studies, systematic reviews,
      economic studies or studies that reported on longer-term outcomes. The key themes
      identified were origin and location of CHs; their place in the continuum of care;
      services provided; effectiveness, efficiency and equity of CHs; and views of
      patients and staff. In general, there was a lack of robust evidence for the role
      of CHs, which is partly due to the ad hoc nature of their development and lack of
      clear strategic vision for their future. Evidence for the effectiveness and
      efficiency of the services provided was limited. Most people admitted to CHs
      appeared to be older, suggesting that admittance to CHs was age-related rather
      than condition-related. CONCLUSION: Overall the literature surveyed was long on
      opinion and short of robust studies on CHs. While lack of evidence on CHs does
      not imply lack of effect, there is an urgent need to develop a research agenda
      that addresses the key issues of health care delivery in the CH setting.

PMID- 17184518
TI  - Quantitative analysis of cell-type specific gene expression in the green alga
      Volvox carteri.
AB  - BACKGROUND: The multicellular alga Volvox carteri possesses only two cell types:
      mortal, motile somatic cells and potentially immortal, immotile reproductive
      cells. It is therefore an attractive model system for studying how cell
      autonomous cytodifferentiation is programmed within a genome. Moreover, there are
      ongoing genome projects both in Volvox carteri and in the closely related
      unicellular alga Chlamydomonas reinhardtii. However, gene sequencing is only the
      beginning. To identify cell-type specific expression and to determine relative
      expression rates, we evaluate the potential of real-time RT-PCR for quantifying
      gene transcript levels. RESULTS: Here we analyze a diversified pool of 39 target
      genes by real-time RT-PCR for each cell type. This gene pool contains previously
      known genes with unknown localization of cellular expression, 28 novel genes
      which are described in this study for the first time, and a few known, cell-type
      specific genes as a control. The respective gene products are, for instance, part
      of photosynthesis, cellular regulation, stress response, or transport processes.
      We provide expression data for all these genes. CONCLUSION: The results show that
      quantitative real-time RT-PCR is a favorable approach to analyze cell-type
      specific gene expression in Volvox, which can be extended to a much larger number
      of genes or to developmental or metabolic mutants. Our expression data also
      provide a basis for a detailed analysis of individual, previously unknown, cell
      type specifically expressed genes.

PMID- 17184519
TI  - A minimally invasive multiple marker approach allows highly efficient detection
      of meningioma tumors.
AB  - BACKGROUND: The development of effective frameworks that permit an accurate
      diagnosis of tumors, especially in their early stages, remains a grand challenge
      in the field of bioinformatics. Our approach uses statistical learning techniques
      applied to multiple antigen tumor antigen markers utilizing the immune system as
      a very sensitive marker of molecular pathological processes. For validation
      purposes we choose the intracranial meningioma tumors as model system since they
      occur very frequently, are mostly benign, and are genetically stable. RESULTS: A
      total of 183 blood samples from 93 meningioma patients (WHO stages I-III) and 90
      healthy controls were screened for seroreactivity with a set of 57 meningioma
      associated antigens. We tested several established statistical learning methods
      on the resulting reactivity patterns using 10-fold cross validation. The best
      performance was achieved by Naive Bayes Classifiers. With this classification
      method, our framework, called Minimally Invasive Multiple Marker (MIMM) approach,
      yielded a specificity of 96.2%, a sensitivity of 84.5%, and an accuracy of 90.3%,
      the respective area under the ROC curve was 0.957. Detailed analysis revealed
      that prediction performs particularly well on low-grade (WHO I) tumors,
      consistent with our goal of early stage tumor detection. For these tumors the
      best classification result with a specificity of 97.5%, a sensitivity of 91.3%,
      an accuracy of 95.6%, and an area under the ROC curve of 0.971 was achieved using
      a set of 12 antigen markers only. This antigen set was detected by a subset
      selection method based on Mutual Information. Remarkably, our study proves that
      the inclusion of non-specific antigens, detected not only in tumor but also in
      normal sera, increases the performance significantly, since non-specific antigens
      contribute additional diagnostic information. CONCLUSION: Our approach offers the
      possibility to screen members of risk groups as a matter of routine such that
      tumors hopefully can be diagnosed immediately after their genesis. The early
      detection will finally result in a higher cure- and lower morbidity-rate.

PMID- 17184520
TI  - Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger
      RNA levels and activity in SAMP8 brain.
AB  - BACKGROUND: Nitric oxide (NO) is a multifunctional molecule synthesized by three
      isozymes of the NO synthase (NOSs) acting as a messenger/modulator and/or a
      potential neurotoxin. In rodents, the role of NOSs in sleep processes and
      throughout aging is now well established. For example, sleep parameters are
      highly deteriorated in senescence accelerated-prone 8 (SAMP8) mice, a useful
      animal model to study aging or age-associated disorders, while the inducible form
      of NOS (iNOS) is down-regulated within the cortex and the sleep-structures of the
      brainstem. Evidence is now increasing for a role of iNOS and resulting oxidative
      stress but not for the constitutive expressed isozyme (nNOS). To better
      understand the role of nNOS in the behavioural impairments observed in SAMP8
      versus SAMR1 (control) animals, we evaluated age-related variations occurring in
      the nNOS expression and activity and nitrites/nitrates (NOx-) levels, in three
      brain areas (n = 7 animals in each group). Calibrated reverse transcriptase (RT)
      and real-time polymerase chain reaction (PCR) and biochemical procedures were
      used. RESULTS: We found that the levels of nNOS mRNA decreased in the cortex and
      the hippocampus of 8- vs 2-month-old animals followed by an increase in 12-vs 8
      month-old animals in both strains. In the brainstem, levels of nNOS mRNA
      decreased in an age-dependent manner in SAMP8, but not in SAMR1. Regional age
      related changes were also observed in nNOS activity. Moreover, nNOS activity in
      hippocampus was found lower in 8-month-old SAMP8 than in SAMR1, while in the
      cortex and the brainstem, nNOS activities increased at 8 months and afterward
      decreased with age in SAMP8 and SAMR1. NOx- levels showed profiles similar to
      nNOS activities in the cortex and the brainstem but were undetectable in the
      hippocampus of SAMP8 and SAMR1. Finally, NOx- levels were higher in the cortex of
      8 month-old SAMP8 than in age-matched SAMR1. CONCLUSION: Concomitant variations
      occurring in NO levels derived from nNOS and iNOS at an early age constitute a
      major factor of risk for sleep and/or memory impairments in SAMP8.

PMID- 17184521
TI  - Financial considerations in the conduct of multi-centre randomised controlled
      trials: evidence from a qualitative study.
AB  - BACKGROUND: Securing and managing finances for multicentre randomised controlled
      trials is a highly complex activity which is rarely considered in the research
      literature. This paper describes the process of financial negotiation and the
      impact of financial considerations in four UK multicentre trials. These trials
      had met, or were on schedule to meet, recruitment targets agreed with their
      public-sector funders. The trials were considered within a larger study examining
      factors which might be associated with trial recruitment (STEPS). METHODS: In
      depth semi-structured telephone interviews were conducted in 2003-04 with 45
      individuals with various responsibilities to one of the four trials. Interviewees
      were recruited through purposive and then snowball sampling. Interview
      transcripts were analysed with the assistance of the qualitative package Atlas
      ti. RESULTS: The data suggest that the UK system of dividing funds into research,
      treatment and NHS support costs brought the trial teams into complicated
      negotiations with multiple funders. The divisions were somewhat malleable and the
      funding system was used differently in each trial. The fact that all funders had
      the potential to influence and shape the trials considered here was an important
      issue as the perspectives of applicants and funders could diverge. The extent and
      range of industry involvement in non-industry-led trials was striking. Three
      broad periods of financial work (foundation, maintenance, and resourcing
      completion) were identified. From development to completion of a trial, the
      trialists had to be resourceful and flexible, adapting to changing internal and
      external circumstances. In each period, trialists and collaborators could face
      changing costs and challenges. Each trial extended the recruitment period; three
      required funding extensions from MRC or HTA. CONCLUSION: This study highlights
      complex financial aspects of planning and conducting trials, especially where
      multiple funders are involved. Recognition of the importance of financial
      stability and of the need for appropriate training in this area should be
      paralleled by further similar research with a broader range of trials, aimed at
      understanding and facilitating the conduct of clinical research.

PMID- 17184523
TI  - Ethnobotanical study of wild edible plants in Derashe and Kucha Districts, South
      Ethiopia.
AB  - The study discussed ethnobotany of and threats to wild edible plants in Derashe
      and Kucha Districts, South Ethiopia. Semi-structured interview, field
      observation, group discussion, market survey, and pair wise ranking were employed
      to gather ethnobotanical data. The information was collected from informants of
      three ethnic groups namely, Kusume, Derashe and Gamo people. The study documented
      66 edible plant species belonging to 54 genera and 34 families. Of the reported
      edibles, 83.3% have more than one use categories. Food, medicine,
      construction/technology, and fuel wood had contributed 79% of the total uses. Of
      the recorded wild edible plant species, 78.8% were reported to be edible both in
      normal and food shortage times. Procurement and use of most edibles were found to
      be age and gender specific. However, species use under various use categories
      does not vary among the communities (Chi2 = 3.89, df = 6, alpha = 0.05 and 1
      alpha = 12.6). The study showed that the majority (62.1%) of the species were
      collected from wooded grassland/or bush land vegetation type. Pair wise ranking
      results indicated that agricultural expansion, over stocking/overgrazing, fuel
      wood collection, and uncontrolled fire setting as principal threats to wild
      edible plants in the study areas. The findings suggest that (i) Public awareness
      and community based management need to be encouraged at all levels in order to
      overcome the threats; (ii) further investigation into nutritional properties of
      all the species reported; and (iii) Since the species are also nutraceutical,
      study on the pharmacological attributes would help to understand their medicinal
      applications. Furthermore, urgent collection of germplasm from areas under human
      pressure is recommended.

PMID- 17184522
TI  - A time- and dose-dependent STAT1 expression system.
AB  - BACKGROUND: The signal transducer and activator of transcription (STAT) family of
      transcription factors mediates a variety of cytokine dependent gene regulations.
      STAT1 has been mainly characterized by its role in interferon (IFN) type I and II
      signaling and STAT1 deficiency leads to high susceptibility to several pathogens.
      For fine-tuned analysis of STAT1 function we established a dimerizer-inducible
      system for STAT1 expression in vitro and in vivo. RESULTS: The functionality of
      the dimerizer-induced STAT1 system is demonstrated in vitro in mouse embryonic
      fibroblasts and embryonic stem cells. We show that this two-vector based system
      is highly inducible and does not show any STAT1 expression in the absence of the
      inducer. Reconstitution of STAT1 deficient cells with inducible STAT1 restores
      IFNgamma-mediated gene induction, antiviral responses and STAT1 activation
      remains dependent on cytokine stimulation. STAT1 expression is induced rapidly
      upon addition of dimerizer and expression levels can be regulated in a dose
      dependent manner. Furthermore we show that in transgenic mice STAT1 can be
      induced upon stimulation with the dimerizer, although only at low levels.
      CONCLUSION: These results prove that the dimerizer-induced system is a powerful
      tool for STAT1 analysis in vitro and provide evidence that the system is suitable
      for the use in transgenic mice. To our knowledge this is the first report for
      inducible STAT1 expression in a time- and dose-dependent manner.

PMID- 17184524
TI  - Effect of long-term exposure of SH-SY5Y cells to morphine: a whole cell proteomic
      analysis.
AB  - BACKGROUND: Opiate addiction reflects plastic changes that endurably alter
      synaptic transmission within relevant neuronal circuits. The biochemical
      mechanisms of these adaptations remain largely unknown and proteomics-based
      approaches could lead to a broad characterization of the molecular events
      underlying adaptations to chronic drug exposure. RESULTS: Thus, we have started
      proteomic analyses of the effects of chronic morphine exposure in a recombinant
      human neuroblastoma SH-SY5Y clone that stably overexpresses the mu-opioid
      receptor. Cells were treated with morphine for 6, 24 and 72 hours, the proteins
      were separated by 2-D gel electrophoresis and stained with Coomassie blue, and
      the protein map was compared with that obtained from untreated cells. Spots
      showing a statistically significant variation were selected for identification
      using mass spectrometric analyses. CONCLUSION: A total of 45 proteins were
      identified, including proteins involved in cellular metabolism, cytoskeleton
      organization, vesicular trafficking, transcriptional and translational
      regulation, and cell signaling.

PMID- 17184526
TI  - Do chiropractic college faculty understand informed consent: a pilot study.
AB  - BACKGROUND: The purpose of this study was to survey full-time faculty at a single
      chiropractic college concerning their knowledge of Institutional Review Board
      (IRB) policies in their institution as they pertain to educational research.
      METHODS: All full-time faculty were invited to participate in an anonymous
      survey. Four scenarios involving educational research were described and
      respondents were asked to select from three possible courses of action for each.
      In addition, respondents were queried about their knowledge of IRB policies, how
      they learned of these policies and about their years of service and departmental
      assignments. RESULTS: The response rate was 55%. In no scenario did the level of
      correct answers by all respondents score higher than 41% and in most, the scores
      were closer to just under 1 in 3. Sixty-five percent of respondents indicated
      they were unsure whether Palmer had any policies in place at all, while 4% felt
      that no such policies were in place. Just over one-quarter (27%) were correct in
      noting that students can decline consent, while more than half (54%) did not know
      whether there were any procedures governing student consent. CONCLUSION: Palmer
      faculty have only modest understanding about institutional policies regarding the
      IRB and human subject research, especially pertaining to educational research.
      The institution needs to develop methods to provide knowledge and training to
      faculty. The results from this pilot study will be instrumental in developing
      better protocols for a study designed to survey the entire chiropractic academic
      community.

PMID- 17184525
TI  - High resolution melting analysis for the rapid and sensitive detection of
      mutations in clinical samples: KRAS codon 12 and 13 mutations in non-small cell
      lung cancer.
AB  - BACKGROUND: The development of targeted therapies has created a pressing clinical
      need for the rapid and robust molecular characterisation of cancers. We describe
      here the application of high-resolution melting analysis (HRM) to screen for KRAS
      mutations in clinical cancer samples. In non-small cell lung cancer, KRAS
      mutations have been shown to identify a group of patients that do not respond to
      EGFR targeted therapies and the identification of these mutations is thus
      clinically important. METHODS: We developed a high-resolution melting (HRM) assay
      to detect somatic mutations in exon 2, notably codons 12 and 13 of the KRAS gene
      using the intercalating dye SYTO 9. We tested 3 different cell lines with known
      KRAS mutations and then examined the sensitivity of mutation detection with the
      cell lines using 189 bp and 92 bp amplicons spanning codons 12 and 13. We then
      screened for KRAS mutations in 30 non-small cell lung cancer biopsies that had
      been previously sequenced for mutations in EGFR exons 18-21. RESULTS: Known KRAS
      mutations in cell lines (A549, HCT116 and RPMI8226) were readily detectable using
      HRM. The shorter 92 bp amplicon was more sensitive in detecting mutations than
      the 189 bp amplicon and was able to reliably detect as little as 5-6% of each
      cell line DNA diluted in normal DNA. Nine of the 30 non-small cell lung cancer
      biopsies had KRAS mutations detected by HRM analysis. The results were confirmed
      by standard sequencing. Mutations in KRAS and EGFR were mutually exclusive.
      CONCLUSION: HRM is a sensitive in-tube methodology to screen for mutations in
      clinical samples. HRM will enable high-throughput screening of gene mutations to
      allow appropriate therapeutic choices for patients and accelerate research aimed
      at identifying novel mutations in human cancer.

PMID- 17184528
TI  - Catharanthus roseus flower extract has wound-healing activity in Sprague Dawley
      rats.
AB  - BACKGROUND: Catharanthus roseus L (C. roseus) has been used to treat a wide
      assortment of diseases including diabetes. The objective of our study was to
      evaluate the antimicrobial and wound healing activity of the flower extract of
      Catharanthus in rats. METHODS: Wound healing activity was determined in rats,
      after administration (100 mg kg-1 day-1) of the ethanol extract of C. roseus
      flower, using excision, incision and dead space wounds models. The animals were
      divided into two groups of 6 each in all the models. In the excision model, group
      1 animals were topically treated with carboxymethyl cellulose as placebo control
      and group 2 received topical application of the ethanol extract of C. roseus at a
      dose of 100 mg/kg body weight/day. In an incision and dead space model group 1
      animals were given normal saline and group 2 received the extract orally at a
      dose of 100 mg kg-1 day-1. Healing was assessed by the rate of wound contraction,
      period of epithelization, tensile strength (skin breaking strength), granulation
      tissue weight, and hydoxyproline content. Antimicrobial activity of the flower
      extract against four microorganisms was also assessed RESULTS: The extract of C.
      roseus significantly increased the wound breaking strength in the incision wound
      model compared with controls (P < 0.001). The extract-treated wounds were found
      to epithelialize faster, and the rate of wound contraction was significantly
      increased in comparison to control wounds (P < 0.001), Wet and dry granulation
      tissue weights, and hydroxyproline content in a dead space wound model increased
      significantly (p < 0.05). Pseudomonas aeruginosa and Staphylococcus aureus
      demonstrated sensitivity to C. roseus CONCLUSION: Increased wound contraction and
      tensile strength, augmented hydroxyproline content along with antimicrobial
      activity support the use of C. roseus in the topical management of wound healing.

PMID- 17184527
TI  - Quality of life in age-related macular degeneration: a review of the literature.
AB  - BACKGROUND: The Age-related Macular Degeneration Alliance International
      commissioned a review of the literature on quality of life (QoL) in macular
      degeneration (MD) with a view to increasing awareness of MD, reducing its impact
      and improving services for people with MD worldwide. METHOD: A systematic review
      was conducted using electronic databases, conference proceedings and key journal
      hand search checks. The resulting 'White Paper' was posted on the AMD Alliance
      website and is reproduced here. REVIEW: MD is a chronic, largely untreatable eye
      condition which leads to loss of central vision needed for tasks such as reading,
      watching TV, driving, recognising faces. It is the most common cause of blindness
      in the Western world. Shock of diagnosis, coupled with lack of information and
      support are a common experience. Incidence of depression is twice that found in
      the community-dwelling elderly, fuelled by functional decline and loss of leisure
      activities. Some people feel suicidal. MD threatens independence, especially when
      comorbidity exacerbates functional limitations. Rehabilitation, including low
      vision aid (LVA) provision and training, peer support and education, can improve
      functional and psychological outcomes but many people do not receive services
      likely to benefit them. Medical treatments, suitable for only a small minority of
      people with MD, can improve vision but most limit progress of MD, at least for a
      time, rather than cure. The White Paper considers difficulties associated with
      inappropriate use of health status measures and misinterpretation of utility
      values as QoL measures: evidence suggests they have poor validity in MD.
      CONCLUSION: There is considerable evidence for the major damage done to QoL by MD
      which is underestimated by health status and utility measures. Medical treatments
      are limited to a small proportion of people. However, much can be done to improve
      QoL by early diagnosis of MD with good communication of prognosis and continuing
      support. Support could include provision of LVAs, peer support, education and
      effective help in adjusting to MD. It is vital that appropriate measures of
      visual function and QoL be used in building a sound evidence base for the
      effectiveness of rehabilitation and treatment.

PMID- 17184529
TI  - Impaired RNA incorporation and dimerization in live attenuated leader-variants of
      SIVmac239.
AB  - BACKGROUND: The 5' untranslated region (UTR) or leader sequence of simian
      immunodeficiency virus (SIVmac239) is multifunctional and harbors the regulatory
      elements for viral replication, persistence, gene translation, expression, and
      the packaging and dimerization of viral genomic RNA (vRNA). We have constructed a
      series of deletions in the SIVmac239 leader sequence in order to determine the
      involvement of this region in both the packaging and dimerization of viral
      genomic RNA. We also assessed the impact of these deletions upon viral
      infectiousness, replication kinetics and gene expression in cell lines and monkey
      peripheral blood mononuclear cells (PBMC). RESULTS: Regions on both sides of the
      major splice donor (SD) were found to be necessary for the efficiency and
      specificity of viral genome packaging. However, stem-loop1 is critical for both
      RNA encapsidation and dimerization. Downstream elements between the splice donor
      and the initiation site of SIV-Gag have additive effects on RNA packaging and
      contribute to a lesser degree to RNA dimerization. The targeted disruption of
      structures on both sides of the SD also severely impacts viral infectiousness,
      gene expression and replication in both CEMx174 cells and rhesus PBMC.
      CONCLUSION: In the leader region of SIVmac239, stem-loop1 functions as the
      primary determinant for both RNA encapsidation and dimerization. Downstream
      elements between the splice donor and the translational initiation site of SIV
      Gag are classified as secondary determinants and play a role in dimerization.
      Collectively, these data signify a linkage between the primary encapsidation
      determinant of SIVmac239 and RNA dimerization.

PMID- 17184530
TI  - Identification of microspore-active promoters that allow targeted manipulation of
      gene expression at early stages of microgametogenesis in Arabidopsis.
AB  - BACKGROUND: The effective functional analysis of male gametophyte development
      requires new tools enabling the spatially and temporally controlled expression of
      both marker genes and modified genes of interest. In particular, promoters
      driving expression at earlier developmental stages including microspores are
      required. RESULTS: Transcriptomic datasets covering four progressive stages of
      male gametophyte development in Arabidopsis were used to select candidate genes
      showing early expression profiles that were male gametophyte-specific. Promoter
      GUS reporter analysis of candidate genes identified three promoters (MSP1, MSP2,
      and MSP3) that are active in microspores and are otherwise specific to the male
      gametophyte and tapetum. The MSP1 and MSP2 promoters were used to successfully
      complement and restore the male transmission of the gametophytic two-in-one (tio)
      mutant that is cytokinesis-defective at first microspore division. CONCLUSION: We
      demonstrate the effective application of MSP promoters as tools that can be used
      to elucidate gametophytic gene functions in microspores in a male-specific
      manner.

PMID- 17184532
TI  - Choroid plexus epithelial monolayers--a cell culture model from porcine brain.
AB  - BACKGROUND: The goal of the present study was to develop an in vitro choroid
      plexus (CP) epithelial cell culture model for studying transport of protein
      mediated drug secretion from blood to cerebrospinal fluid (CSF) and vice versa.
      METHODS: Cells were isolated by mechanical and enzymatic treatment of freshly
      isolated porcine plexus tissue. Epithelial cell monolayers were grown and CSF
      secretion and transepithelial resistance were determined. The expression of f
      actin as well as the choroid plexus marker protein transthyretin (TTR), were
      assessed. The expression of the export proteins p-glycoprotein (Pgp, Abcb1) and
      multidrug resistance protein 1 (Mrp1, Abcc1) was studied by RT-PCR, Western-blot
      and immunofluorescence techniques and their functional activity was assessed by
      transport and uptake experiments. RESULTS: Choroid plexus epithelial cells were
      isolated in high purity and grown to form confluent monolayers. Filter-grown
      monolayers displayed transendothelial resistance (TEER) values in the range of
      100 to 150 ohms cm2. Morphologically, the cells showed the typical net work of f
      actin and expressed TTR at a high rate. The cultured cells were able to secrete
      CSF at a rate of 48.2 +/- 4.6 microl/cm2/h over 2-3 hours. The ABC-export protein
      Mrp1 was expressed in the basolateral (blood-facing) membranes of cell monolayers
      and intact tissue. P-glycoprotein showed only low expression within the apical
      (CSF directed) membrane but was located more in sub-apical cell compartments.
      This finding was paralleled by the lack of directed excretion of p-glycoprotein
      substrates, verapamil and rhodamine 123. CONCLUSION: It was demonstrated that CP
      epithelium can be isolated and cultured, with cells growing into intact
      monolayers, fully differentiating and with properties resembling the tissue in
      vivo. Thus, the established primary porcine CP model, allowing investigation of
      complex transport processes, can be used as a reliable tool for analysis of
      xenobiotic transport across the blood-cerebrospinal fluid barrier (BCSFB).

PMID- 17184531
TI  - A method for estimation of elasticities in metabolic networks using steady state
      and dynamic metabolomics data and linlog kinetics.
AB  - BACKGROUND: Dynamic modeling of metabolic reaction networks under in vivo
      conditions is a crucial step in order to obtain a better understanding of the
      (dis)functioning of living cells. So far dynamic metabolic models generally have
      been based on mechanistic rate equations which often contain so many parameters
      that their identifiability from experimental data forms a serious problem.
      Recently, approximative rate equations, based on the linear logarithmic (linlog)
      format have been proposed as a suitable alternative with fewer parameters.
      RESULTS: In this paper we present a method for estimation of the kinetic model
      parameters, which are equal to the elasticities defined in Metabolic Control
      Analysis, from metabolite data obtained from dynamic as well as steady state
      perturbations, using the linlog kinetic format. Additionally, we address the
      question of parameter identifiability from dynamic perturbation data in the
      presence of noise. The method is illustrated using metabolite data generated with
      a dynamic model of the glycolytic pathway of Saccharomyces cerevisiae based on
      mechanistic rate equations. Elasticities are estimated from the generated data,
      which define the complete linlog kinetic model of the glycolysis. The effect of
      data noise on the accuracy of the estimated elasticities is presented. Finally,
      identifiable subset of parameters is determined using information on the standard
      deviations of the estimated elasticities through Monte Carlo (MC) simulations.
      CONCLUSION: The parameter estimation within the linlog kinetic framework as
      presented here allows the determination of the elasticities directly from
      experimental data from typical dynamic and/or steady state experiments. These
      elasticities allow the reconstruction of the full kinetic model of Saccharomyces
      cerevisiae, and the determination of the control coefficients. MC simulations
      revealed that certain elasticities are potentially unidentifiable from dynamic
      data only. Addition of steady state perturbation of enzyme activities solved this
      problem.

PMID- 17184533
TI  - Usability of a barcode scanning system as a means of data entry on a PDA for self
      report health outcome questionnaires: a pilot study in individuals over 60 years
      of age.
AB  - BACKGROUND: Throughout the medical and paramedical professions, self-report
      health status questionnaires are used to gather patient-reported outcome
      measures. The objective of this pilot study was to evaluate in individuals over
      60 years of age the usability of a PDA-based barcode scanning system with a text
      to-speech synthesizer to collect data electronically from self-report health
      outcome questionnaires. METHODS: Usability of the system was tested on a sample
      of 24 community-living older adults (7 men, 17 women) ranging in age from 63 to
      93 years. After receiving a brief demonstration on the use of the barcode
      scanner, participants were randomly assigned to complete two sets of 16 questions
      using the bar code wand scanner for one set and a pen for the other. Usability
      was assessed using directed interviews with a usability questionnaire and
      performance-based metrics (task times, errors, sources of errors). RESULTS:
      Overall, participants found barcode scanning easy to learn, easy to use, and
      pleasant. Participants were marginally faster in completing the 16 survey
      questions when using pen entry (20/24 participants). The mean response time with
      the barcode scanner was 31 seconds longer than traditional pen entry for a subset
      of 16 questions (p = 0.001). The responsiveness of the scanning system, expressed
      as first scan success rate, was less than perfect, with approximately one-third
      of first scans requiring a rescan to successfully capture the data entry. The
      responsiveness of the system can be explained by a combination of factors such as
      the location of the scanning errors, the type of barcode used as an answer field
      in the paper version, and the optical characteristics of the barcode scanner.
      CONCLUSION: The results presented in this study offer insights regarding the
      feasibility, usability and effectiveness of using a barcode scanner with older
      adults as an electronic data entry method on a PDA. While participants in this
      study found their experience with the barcode scanning system enjoyable and
      learned to become proficient in its use, the responsiveness of the system
      constitutes a barrier to wide-scale use of such a system. Optimizing the
      graphical presentation of the information on paper should significantly increase
      the system's responsiveness.

PMID- 17184534
TI  - Plasma organochlorine concentrations and bone ultrasound measurements: a cross
      sectional study in peri-and postmenopausal Inuit women from Greenland.
AB  - BACKGROUND: Inuit women are highly exposed through their traditional seafood
      based diet to organochlorine compounds, some of them displaying endocrine
      disrupting properties. We hypothesized that this exposure might be related to
      bone characteristics that are altered in osteoporosis, because hormone deficiency
      is a known risk factor for the disease. METHODS: We measured quantitative
      ultrasound parameters (QUS) at the right calcaneum of 153 peri- and
      postmenopausal Inuit women (49-64 year old) from Nuuk, Greenland, and
      investigated the relation between these parameters and plasma organochlorine
      concentrations. We used high-resolution gas chromatography with electron capture
      detection to analyze plasma samples for 14 polychlorinated biphenyls (PCB)
      congeners and 11 chlorinated pesticides and metabolites. We analysed morning
      urine samples for cadmium, a potential confounder, by atomic absorption
      spectrometry. We used a validated questionnaire to document dietary and lifestyle
      habits as well as reproductive and medical histories. RESULTS: Concentrations of
      PCB 153, a surrogate of exposure to most organochlorines present in plasma
      samples, were inversely correlated to QUS parameters in univariate analyses (p <
      0.001). However, PCB 153 concentrations were not associated with QUS values in
      multivariate analyses that comprised potential confounding factors such as age,
      body weight, former oral contraceptive use and current hormone replacement
      therapy (HRT) use, which were all significant predictors of bone stiffness (total
      R2 = 0.39; p < 0.001). CONCLUSION: Overall we found little evidence that
      organochlorines exposure is related to osteoporosis in Greenlandic Inuit women,
      but the hypothesis that exposure to dioxin-like compounds might be linked to
      decreased bone quality and osteoporosis deserves further attention.

PMID- 17184535
TI  - The impact of rheumatoid arthritis on foot function in the early stages of
      disease: a clinical case series.
AB  - BACKGROUND: Foot involvement occurs early in rheumatoid arthritis but the extent
      to which this impacts on the structure and function leading to impairment and
      foot related disability is unknown. The purpose of this study was to compare
      clinical disease activity, impairment, disability, and foot function in normal
      and early rheumatoid arthritis (RA) feet using standardised clinical measures and
      3D gait analysis. METHODS: Twelve RA patients with disease duration < or =2 years
      and 12 able-bodied adults matched for age and sex underwent 3D gait analysis to
      measure foot function. Disease impact was measured using the Leeds Foot impact
      Scale (LFIS) along with standard clinical measures of disease activity, pain and
      foot deformity. For this small sample, the mean differences between the groups
      and associated confidence intervals were calculated using the t distribution
      RESULTS: Moderate-to-high foot impairment and related disability were detected
      amongst the RA patients. In comparison with age- and sex-matched controls, the
      patients with early RA walked slower (1.05 m/s Vs 1.30 m/s) and had a longer
      double-support phase (19.3% Vs 15.8%). In terminal stance, the heel rise angle
      was reduced in the patients in comparison with normal (-78.9 degrees Vs -85.7
      degrees). Medial arch height was lower and peak eversion in stance greater in the
      RA patients. The peak ankle plantarflexion power profile was lower in the
      patients in comparison with the controls (3.4 W/kg Vs 4.6 W/kg). Pressure
      analysis indicated that the RA patients had a reduced lesser toe contact area
      (7.6 cm2 Vs 8.1 cm2), elevated peak forefoot pressure (672 kPa Vs 553 kPa) and a
      larger mid-foot contact area (24.6 cm2 Vs 19.4 cm2). CONCLUSION: Analysis
      detected small but clinically important changes in foot function in a small
      cohort of RA patients with disease duration <2 years. These were accompanied by
      active joint disease and impairment and disability.

PMID- 17184536
TI  - Neck ligament strength is decreased following whiplash trauma.
AB  - BACKGROUND: Previous clinical studies have documented successful neck pain relief
      in whiplash patients using nerve block and radiofrequency ablation of facet joint
      afferents, including capsular ligament nerves. No previous study has documented
      injuries to the neck ligaments as determined by altered dynamic mechanical
      properties due to whiplash. The goal of the present study was to determine the
      dynamic mechanical properties of whiplash-exposed human cervical spine ligaments.
      Additionally, the present data were compared to previously reported control data.
      The ligaments included the anterior and posterior longitudinal, capsular, and
      interspinous and supraspinous ligaments, middle-third disc, and ligamentum
      flavum. METHODS: A total of 98 bone-ligament-bone specimens (C2-C3 to C7-T1) were
      prepared from six cervical spines following 3.5, 5, 6.5, and 8 g rear impacts and
      pre- and post-impact flexibility testing. The specimens were elongated to failure
      at a peak rate of 725 (SD 95) mm/s. Failure force, elongation, and energy
      absorbed, as well as stiffness were determined. The mechanical properties were
      statistically compared among ligaments, and to the control data (significance
      level: P < 0.05; trend: P < 0.1). The average physiological ligament elongation
      was determined using a mathematical model. RESULTS: For all whiplash-exposed
      ligaments, the average failure elongation exceeded the average physiological
      elongation. The highest average failure force of 204.6 N was observed in the
      ligamentum flavum, significantly greater than in middle-third disc and
      interspinous and supraspinous ligaments. The highest average failure elongation
      of 4.9 mm was observed in the interspinous and supraspinous ligaments,
      significantly greater than in the anterior longitudinal ligament, middle-third
      disc, and ligamentum flavum. The average energy absorbed ranged from 0.04 J by
      the middle-third disc to 0.44 J by the capsular ligament. The ligamentum flavum
      was the stiffest ligament, while the interspinous and supraspinous ligaments were
      most flexible. The whiplash-exposed ligaments had significantly lower (P = 0.036)
      failure force, 149.4 vs. 186.0 N, and a trend (P = 0.078) towards less energy
      absorption capacity, 308.6 vs. 397.0 J, as compared to the control data.
      CONCLUSION: The present decreases in neck ligament strength due to whiplash
      provide support for the ligament-injury hypothesis of whiplash syndrome.

PMID- 17184537
TI  - The major histocompatibility complex (Mhc) class IIB region has greater genomic
      structural flexibility and diversity in the quail than the chicken.
AB  - BACKGROUND: The quail and chicken major histocompatibility complex (Mhc) genomic
      regions have a similar overall organization but differ markedly in that the quail
      has an expanded number of duplicated class I, class IIB, natural killer (NK)
      receptor-like, lectin-like and BG genes. Therefore, the elucidation of genetic
      factors that contribute to the greater Mhc diversity in the quail would help to
      establish it as a model experimental animal in the investigation of avian Mhc
      associated diseases. AIMS AND APPROACHES: The main aim here was to characterize
      the genetic and genomic features of the transcribed major quail MhcIIB (CojaIIB)
      region that is located between the Tapasin and BRD2 genes, and to compare our
      findings to the available information for the chicken MhcIIB (BLB). We used four
      approaches in the study of the quail MhcIIB region, (1) haplotype analyses with
      polymorphic loci, (2) cloning and sequencing of the RT-PCR CojaIIB products from
      individuals with different haplotypes, (3) genomic sequencing of the CojaIIB
      region from the individuals with the different haplotypes, and (4) phylogenetic
      and duplication analysis to explain the variability of the region between the
      quail and the chicken. RESULTS: Our results show that the Tapasin-BRD2 segment of
      the quail Mhc is highly variable in length and in gene transcription intensity
      and content. Haplotypic sequences were found to vary in length between 4 to 11
      kb. Tapasin-BRD2 segments contain one or two major transcribed CojaIIBs that were
      probably generated by segmental duplications involving c-type lectin-like genes
      and NK receptor-like genes, gene fusions between two CojaIIBs and transpositions
      between the major and minor CojaIIB segments. The relative evolutionary speed for
      generating the MhcIIBs genomic structures from the ancestral BLB2 was estimated
      to be two times faster in the quail than in the chicken after their separation
      from a common ancestor. Four types of genomic rearrangement elements (GRE),
      composed of simple tandem repeats (STR), were identified in the MhcIIB genomic
      segment located between the Tapasin-BRD2 genes. The GREs have many more STR
      numbers in the quail than in the chicken that displays strong linkage
      disequilibrium. CONCLUSION: This study suggests that the Mhc classIIB region has
      a flexible genomic structure generated by rearrangement elements and rapid SNP
      accumulation probably as a consequence of the quail adapting to environmental
      conditions and pathogens during its migratory history after its divergence from
      the chicken.

PMID- 17184538
TI  - An ecometric analysis of neighbourhood cohesion.
AB  - BACKGROUND: It is widely believed that the social environment has an important
      influence on health, but there is less certainty about how to measure specific
      factors within the social environment that could link the neighbourhood of
      residence to a health outcome. The objectives of the study were to examine the
      underlying constructs captured by an adapted version of Buckner's neighbourhood
      cohesion scale, and to assess the reliability of the scale at the small-area
      level by combining ecometric methodology with ordinal modelling of a five-point
      scale. METHODS: Data were analysed from 11,078 participants in the Caerphilly
      Health and Social Needs Study, who were sampled from within 325 UK census
      enumeration districts in Caerphilly county borough, Wales, UK. The responses of
      interest came from 15 question items designed to capture different facets of
      neighbourhood cohesion. Factor analysis was used to identify constructs
      underlying the neighbourhood cohesion item responses. Using a multilevel
      ecometric model, the variability present in these ordinal responses was
      decomposed into contextual, compositional, item-level and residual components.
      RESULTS: Two constructs labelled neighbourhood belonging and social cohesion were
      identified, and variability in both constructs was modelled at each level of the
      multilevel structure. The intra-neighbourhood correlations were 6.4% and 1.0% for
      the neighbourhood belonging and social cohesion subscales, respectively. Given
      the large sample size, contextual neighbourhood cohesion scores can be estimated
      reliably. The wide variation in the observed frequency of occurence of the scale
      item activities suggests that the two subscales have desirable ecometric
      properties. Further, the majority of between-neighbourhood variation is not
      explained by the socio-demographic characteristics of the individual respondents.
      CONCLUSION: Assessment of the properties of the adapted neighbourhood cohesion
      scale using factor analysis and ecometric analysis extended to an ordinal scale
      has shown that the items allow fine discrimination between individuals. However,
      large sample sizes are needed in order to accurately estimate contextual
      neighbourhood cohesion. The scale is therefore appropriate for use in the
      measurement of neighbourhood cohesion at small-area-level in future studies of
      neighbourhoods and health.

PMID- 17184539
TI  - Tobacco harm reduction: an alternative cessation strategy for inveterate smokers.
AB  - According to the Centers for Disease Control and Prevention, about 45 million
      Americans continue to smoke, even after one of the most intense public health
      campaigns in history, now over 40 years old. Each year some 438,000 smokers die
      from smoking-related diseases, including lung and other cancers, cardiovascular
      disorders and pulmonary diseases. Many smokers are unable--or at least unwilling-
      to achieve cessation through complete nicotine and tobacco abstinence; they
      continue smoking despite the very real and obvious adverse health consequences.
      Conventional smoking cessation policies and programs generally present smokers
      with two unpleasant alternatives: quit, or die. A third approach to smoking
      cessation, tobacco harm reduction, involves the use of alternative sources of
      nicotine, including modern smokeless tobacco products. A substantial body of
      research, much of it produced over the past decade, establishes the scientific
      and medical foundation for tobacco harm reduction using smokeless tobacco
      products. This report provides a description of traditional and modern smokeless
      tobacco products, and of the prevalence of their use in the United States and
      Sweden. It reviews the epidemiologic evidence for low health risks associated
      with smokeless use, both in absolute terms and in comparison to the much higher
      risks of smoking. The report also describes evidence that smokeless tobacco has
      served as an effective substitute for cigarettes among Swedish men, who
      consequently have among the lowest smoking-related mortality rates in the
      developed world. The report documents the fact that extensive misinformation
      about ST products is widely available from ostensibly reputable sources,
      including governmental health agencies and major health organizations. The
      American Council on Science and Health believes that strong support of tobacco
      harm reduction is fully consistent with its mission to promote sound science in
      regulation and in public policy, and to assist consumers in distinguishing real
      health threats from spurious health claims. As this report documents, there is a
      strong scientific and medical foundation for tobacco harm reduction, and it shows
      great potential as a public health strategy to help millions of smokers.

PMID- 17184541
TI  - Effects of a single administration of prostaglandin F2alpha, or a combination of
      prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in
      dairy cows 3-5 weeks post partum, a randomized, double-blind clinical trial.
AB  - BACKGROUND: Delayed uterine involution has negative effects on the fertility of
      cows; use of prostaglandin F2alpha alone as a single treatment has not been shown
      to consistently improve fertility. Combined administration of PGF2alpha and PGE2
      increased uterine pressure in healthy cows. We hypothesized, that the combination
      of both prostaglandins would accelerate uterine involution and have, therefore, a
      positive effect on fertility variables. In commercial dairy farming, the benefit
      of a single post partum combined prostaglandin treatment should be demonstrated.
      METHODS: 383 cows from commercial dairy farms were included in this study.
      Uterine size and secretion were evaluated at treatment 21-35 days post partum and
      14 days later. Cows were randomly allocated to one of three treatment groups:
      PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the
      study, the following reproduction variables were recorded: Interval from calving
      to first insemination, days open, number of artificial inseminations (AI) to
      conception; subsequent treatment of uterus, subsequent treatment of ovaries.
      Plasma progesterone level at time of treatment was used as a covariable. For
      continuous measurements, analysis of variance was performed. Fisher's exact test
      for categorical non-ordered data and exact Kruskal-Wallis test for ordered data
      were used; pairwise group comparisons with Bonferroni adjustment of significance
      level were performed. RESULTS: There was no significant difference among
      treatment groups in uterine size. Furthermore, there was no significant
      difference among treatments concerning days open, number of AI, and subsequent
      treatment of uterus and ovaries. Days from calving to first insemination tended
      to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in
      combination than for the placebo-group (P = 0.024). CONCLUSION: The results of
      this study indicate that the administration of PGF2alpha or a combination of
      PGF2alpha and PGE2 21 to 35 days post partum had no beneficial effect upon
      measured fertility variables. The exception was a tendency for a shorter interval
      from calving to first insemination after administration of the combination of
      PGF2alpha and PGE2, as compared to the placebo group. Further research should be
      done in herds with reduced fertility and/or an increased incidence of postpartum
      vaginal discharge.

PMID- 17184540
TI  - Tenofovir treatment augments anti-viral immunity against drug-resistant SIV
      challenge in chronically infected rhesus macaques.
AB  - BACKGROUND: Emergence of drug-resistant strains of human immunodeficiency virus
      type 1 (HIV-1) is a major obstacle to successful antiretroviral therapy (ART) in
      HIV-infected patients. Whether antiviral immunity can augment ART by suppressing
      replication of drug-resistant HIV-1 in humans is not well understood, but can be
      explored in non-human primates infected with simian immunodeficiency virus (SIV).
      Rhesus macaques infected with live, attenuated SIV develop robust SIV-specific
      immune responses but remain viremic, often at low levels, for periods of months
      to years, thus providing a model in which to evaluate the contribution of
      antiviral immunity to drug efficacy. To investigate the extent to which SIV
      specific immune responses augment suppression of drug-resistant SIV, rhesus
      macaques infected with live, attenuated SIVmac239Deltanef were treated with the
      reverse transcriptase (RT) inhibitor tenofovir, and then challenged with
      pathogenic SIVmac055, which has a five-fold reduced sensitivity to tenofovir.
      RESULTS: Replication of SIVmac055 was detected in untreated macaques infected
      with SIVmac239Deltanef, and in tenofovir-treated, naive control macaques. The
      majority of macaques infected with SIVmac055 experienced high levels of plasma
      viremia, rapid CD4+ T cell loss and clinical disease progression. By comparison,
      macaques infected with SIVmac239Deltanef and treated with tenofovir showed no
      evidence of replicating SIVmac055 in plasma using allele-specific real-time PCR
      assays with a limit of sensitivity of 50 SIV RNA copies/ml plasma. These animals
      remained clinically healthy with stable CD4+ T cell counts during three years of
      follow-up. Both the tenofovir-treated and untreated macaques infected with
      SIVmac239Deltanef had antibody responses to SIV gp130 and p27 antigens and SIV
      specific CD8+ T cell responses prior to SIVmac055 challenge, but only those
      animals receiving concurrent treatment with tenofovir resisted infection with
      SIVmac055. CONCLUSION: These results support the concept that anti-viral immunity
      acts synergistically with ART to augment drug efficacy by suppressing replication
      of viral variants with reduced drug sensitivity. Treatment strategies that seek
      to combine immunotherapeutic intervention as an adjunct to antiretroviral drugs
      may therefore confer added benefit by controlling replication of HIV-1, and
      reducing the likelihood of treatment failure due to the emergence of drug
      resistant virus, thereby preserving treatment options.

PMID- 17184542
TI  - CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a
      California population.
AB  - BACKGROUND: Neural tube defects (NTDs) are among the most common of all human
      congenital defects. Over the last two decades, accumulating evidence has made it
      clear that periconceptional intake of folic acid can significantly reduce the
      risk of NTD affected pregnancies. This beneficial effect may be related to the
      ability of folates to donate methyl groups for critical physiological reactions.
      Choline is an essential nutrient and it is also a methyl donor critical for the
      maintenance of cell membrane integrity and methyl metabolism. Perturbations in
      choline metabolism in vitro have been shown to induce NTDs in mouse embryos.
      METHODS: This study investigated whether single nucleotide polymorphisms (SNPs)
      in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase
      (PCYT1A) gene were risk factors for spina bifida. Fluorescence-based allelic
      discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388
      (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109. The study
      population consisted of 103 infants with spina bifida and 338 non-malformed
      control infants who were born in selected California counties in the period 1989
      1991. RESULTS: The CHKA SNP hCV1562388 genotypes with at least one C allele were
      associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38
      0.94). The PCYT1A SNP rs939883 genotype AA was associated with a twofold
      increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97-3.67). These
      gene-only effects were not substantially modified by analytic consideration to
      maternal periconceptional choline intake. CONCLUSION: Our analyses showed
      genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show
      evidence of gene-nutrient interactions. The underlying mechanisms are yet to be
      resolved.

PMID- 17184544
TI  - Serum calcitonin negative medullary thyroid carcinoma.
AB  - BACKGROUND: Medullary thyroid carcinomas (MTC) constitute about 5 to 7% of
      thyroid neoplasms. They originate from parafollicular C cells which produce
      Calcitonin, a hormone which has an impact on calcium metabolism and represents
      the biochemical activity of MTC. In rare cases pre-operative serum calcitonin can
      be negative. CASE PRESENTATION: We report on a 73-year-old female patient with a
      rare case of a serum calcitonin negative medullary thyroid carcinoma who suffered
      fulminant post-operative course and died of multiple metastasis. CONCLUSION: This
      case shows that in very rare cases MTCs do not secrete calcitonin making
      diagnosis and tumour follow-up difficult. To this date, only few reports
      describing this combination of circumstances were found in the English
      literature.

PMID- 17184543
TI  - Multiple independent evolutionary solutions to core histone gene regulation.
AB  - BACKGROUND: Core histone genes are periodically expressed along the cell cycle
      and peak during S phase. Core histone gene expression is deeply evolutionarily
      conserved from the yeast Saccharomyces cerevisiae to human. RESULTS: We evaluated
      the evolutionary dynamics of the specific regulatory mechanisms that give rise to
      the conserved histone regulatory phenotype. In contrast to the conservation of
      core histone gene expression patterns, the core histone regulatory machinery is
      highly divergent between species. There has been substantial evolutionary
      turnover of cis-regulatory sequence motifs along with the transcription factors
      that bind them. The regulatory mechanisms employed by members of the four core
      histone families are more similar within species than within gene families. The
      presence of species-specific histone regulatory mechanisms is opposite to what is
      seen at the protein sequence level. Core histone proteins are more similar within
      families, irrespective of their species of origin, than between families, which
      is consistent with the shared common ancestry of the members of individual
      histone families. Structure and sequence comparisons between histone families
      reveal that H2A and H2B form one related group whereas H3 and H4 form a distinct
      group, which is consistent with the nucleosome assembly dynamics. CONCLUSION: The
      dissonance between the evolutionary conservation of the core histone gene
      regulatory phenotypes and the divergence of their regulatory mechanisms indicates
      a highly dynamic mode of regulatory evolution. This distinct mode of regulatory
      evolution is probably facilitated by a solution space for promoter sequences, in
      terms of functionally viable cis-regulatory sites, that is substantially greater
      than that of protein sequences.

PMID- 17184545
TI  - Coronary arterial fistulas.
AB  - A coronary arterial fistula is a connection between one or more of the coronary
      arteries and a cardiac chamber or great vessel. This is a rare defect and usually
      occurs in isolation. Its exact incidence is unknown. The majority of these
      fistulas are congenital in origin although they may occasionally be detected
      after cardiac surgery. They do not usually cause symptoms or complications in the
      first two decades, especially when small. After this age, the frequency of both
      symptoms and complications increases. Complications include 'steal' from the
      adjacent myocardium, thrombosis and embolism, cardiac failure, atrial
      fibrillation, rupture, endocarditis/endarteritis and arrhythmias. Thrombosis
      within the fistula is rare but may cause acute myocardial infarction, paroxysmal
      atrial fibrillation and ventricular arrhythmias. Spontaneous rupture of the
      aneurysmal fistula causing haemopericardium has also been reported. The main
      differential diagnosis is patent arterial duct, although other congenital
      arteriovenous shunts need to be excluded. Whilst two-dimensional echocardiography
      helps to differentiate between the different shunts, coronary angiography is the
      main diagnostic tool for the delineation of the anatomy. Surgery was the
      traditional method of treatment but nowadays catheter closure is recommended
      using a variety of closure devices, such as coils, or other devices. With the
      catheter technique, the results are excellent with infrequent complications.

PMID- 17184548
TI  - The three-dimensional easy morphological (3-DEMO) classification of scoliosis,
      part II: Repeatability.
AB  - BACKGROUND: In the first part of this study we proposed a new classification
      approach for spinal deformities (3-DEMO). To be valid, a classification needs to
      overcome the repeatability issue which is inherent both in the used
      classificatory system and in the measured object. AIM: The aim of this study is
      to present procedures and results obtained within the repeatability of 3-DEMO
      classification for scoliosis analysis. METHOD: We acquired the data of 100
      pathological and 20 normal spines with an optoelectronic system (AUSCAN) and of
      two dummies with simulated spine deformity. On the obtained 3D reconstruction of
      the spine, we considered the coronal view with a spinal reference system (Top
      View) and its three related parameters, defined in part I, constituting the 3
      DEMO classification. We calculated the repeatability coefficient for the subjects
      (two acquisitions for each subject with a time interval of 26 +/- 12 sec),
      whereas we evaluated the system measurement error calculating the standard
      deviation of 50 consecutive acquisitions for each dummy. RESULTS: Comparing the
      results of the two types of acquisition, it emerged that the main part of
      parameters variability was due to postural adjustments The proportion of
      agreement for the 3-DEMO parameters gives a k value above 0.8; almost 10% of
      patients changed classification because of postural adjustments, but none had a
      "mirror-like" variation nor a change in more of one parameter at a time
      Repeatability coefficient is lower than the previously calculated normative
      limits. DISCUSSION: The 3-DEMO classification has a high repeatability when
      evaluated with an optoelectronic system such as the AUSCAN System, whose
      systematic error is very low. This means that the implied physiological
      phenomenon is consistent and overcomes the postural variability inherent in the
      measured object (normal or pathological subject).

PMID- 17184547
TI  - Three-dimensional morphology and gene expression in the Drosophila blastoderm at
      cellular resolution II: dynamics.
AB  - BACKGROUND: To accurately describe gene expression and computationally model
      animal transcriptional networks, it is essential to determine the changing
      locations of cells in developing embryos. RESULTS: Using automated image analysis
      methods, we provide the first quantitative description of temporal changes in
      morphology and gene expression at cellular resolution in whole embryos, using the
      Drosophila blastoderm as a model. Analyses based on both fixed and live embryos
      reveal complex, previously undetected three-dimensional changes in nuclear
      density patterns caused by nuclear movements prior to gastrulation. Gene
      expression patterns move, in part, with these changes in morphology, but
      additional spatial shifts in expression patterns are also seen, supporting a
      previously proposed model of pattern dynamics based on the induction and
      inhibition of gene expression. We show that mutations that disrupt either the
      anterior/posterior (a/p) or the dorsal/ventral (d/v) transcriptional cascades
      alter morphology and gene expression along both the a/p and d/v axes in a way
      suggesting that these two patterning systems interact via both transcriptional
      and morphological mechanisms. CONCLUSION: Our work establishes a new strategy for
      measuring temporal changes in the locations of cells and gene expression patterns
      that uses fixed cell material and computational modeling. It also provides a
      coordinate framework for the blastoderm embryo that will allow increasingly
      accurate spatio-temporal modeling of both the transcriptional control network and
      morphogenesis.

PMID- 17184549
TI  - Evolutionary conservation of domain-domain interactions.
AB  - BACKGROUND: Recently, there has been much interest in relating domain-domain
      interactions (DDIs) to protein-protein interactions (PPIs) and vice versa, in an
      attempt to understand the molecular basis of PPIs. RESULTS: Here we map
      structurally derived DDIs onto the cellular PPI networks of different organisms
      and demonstrate that there is a catalog of domain pairs that is used to mediate
      various interactions in the cell. We show that these DDIs occur frequently in
      protein complexes and that homotypic interactions (of a domain with itself) are
      abundant. A comparison of the repertoires of DDIs in the networks of Escherichia
      coli, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster,
      and Homo sapiens shows that many DDIs are evolutionarily conserved. CONCLUSION:
      Our results indicate that different organisms use the same 'building blocks' for
      PPIs, suggesting that the functionality of many domain pairs in mediating protein
      interactions is maintained in evolution.

PMID- 17184546
TI  - Three-dimensional morphology and gene expression in the Drosophila blastoderm at
      cellular resolution I: data acquisition pipeline.
AB  - BACKGROUND: To model and thoroughly understand animal transcription networks, it
      is essential to derive accurate spatial and temporal descriptions of developing
      gene expression patterns with cellular resolution. RESULTS: Here we describe a
      suite of methods that provide the first quantitative three-dimensional
      description of gene expression and morphology at cellular resolution in whole
      embryos. A database containing information derived from 1,282 embryos is released
      that describes the mRNA expression of 22 genes at multiple time points in the
      Drosophila blastoderm. We demonstrate that our methods are sufficiently accurate
      to detect previously undescribed features of morphology and gene expression. The
      cellular blastoderm is shown to have an intricate morphology of nuclear density
      patterns and apical/basal displacements that correlate with later well-known
      morphological features. Pair rule gene expression stripes, generally considered
      to specify patterning only along the anterior/posterior body axis, are shown to
      have complex changes in stripe location, stripe curvature, and expression level
      along the dorsal/ventral axis. Pair rule genes are also found to not always
      maintain the same register to each other. CONCLUSION: The application of these
      quantitative methods to other developmental systems will likely reveal many other
      previously unknown features and provide a more rigorous understanding of
      developmental regulatory networks.

PMID- 17184550
TI  - Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20
      mg in high-risk patients with hypercholesterolemia--Prospective study to evaluate
      the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR).
AB  - BACKGROUND: Many patients at high risk of cardiovascular disease do not achieve
      recommended low-density lipoprotein cholesterol (LDL-C) goals. This study
      compared the efficacy and safety of low doses of rosuvastatin (10 mg) and
      atorvastatin (20 mg) in high-risk patients with hypercholesterolemia. METHODS: A
      total of 996 patients with hypercholesterolemia (LDL-C > or = 3.4 and < 5.7
      mmol/L [130 and 220 mg/dL]) and coronary heart disease (CHD), atherosclerosis, or
      a CHD-risk equivalent were randomized to once-daily rosuvastatin 10 mg or
      atorvastatin 20 mg. The primary endpoint was the percentage change from baseline
      in LDL-C levels at 6 weeks. Secondary endpoints included LDL-C goal achievement
      (National Cholesterol Education Program Adult Treatment Panel III [NCEP ATP III]
      goal < 100 mg/dL; 2003 European goal < 2.5 mmol/L for patients with
      atherosclerotic disease, type 2 diabetes, or at high risk of cardiovascular
      events, as assessed by a Systematic COronary Risk Evaluation (SCORE) risk > or =
      5% or 3.0 mmol/L for all other patients), changes in other lipids and
      lipoproteins, cost-effectiveness, and safety. RESULTS: Rosuvastatin 10 mg reduced
      LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs.
      42.7%, p < 0.05). Significantly more patients achieved NCEP ATP III and 2003
      European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 20 mg
      (68.8% vs. 62.5%, p < 0.05; 68.0% vs. 63.3%, p < 0.05, respectively). High
      density lipoprotein cholesterol was increased significantly with rosuvastatin 10
      mg versus atorvastatin 20 mg (6.4% vs. 3.1%, p < 0.001). Lipid ratios and levels
      of apolipoprotein A-I also improved more with rosuvastatin 10 mg than with
      atorvastatin 20 mg. The use of rosuvastatin 10 mg was also cost-effective
      compared with atorvastatin 20 mg in both a US and a UK setting. Both treatments
      were well tolerated, with a similar incidence of adverse events (rosuvastatin 10
      mg, 27.5%; atorvastatin 20 mg, 26.1%). No cases of rhabdomyolysis, liver, or
      renal insufficiency were recorded. CONCLUSION: In high-risk patients with
      hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin
      20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other
      lipid parameters. Both treatments were well tolerated.

PMID- 17184551
TI  - The celiac ganglion modulates LH-induced inhibition of androstenedione release in
      late pregnant rat ovaries.
AB  - BACKGROUND: Although the control of ovarian production of steroid hormones is
      mainly of endocrine nature, there is increasing evidence that the nervous system
      also influences ovarian steroidogenic output. The purpose of this work was to
      study whether the celiac ganglion modulates, via the superior ovarian nerve, the
      anti-steroidogenic effect of LH in the rat ovary. Using mid- and late-pregnant
      rats, we set up to study: 1) the influence of the noradrenergic stimulation of
      the celiac ganglion on the ovarian production of the luteotropic hormone
      androstenedione; 2) the modulatory effect of noradrenaline at the celiac ganglion
      on the anti-steroidogenic effect of LH in the ovary; and 3) the involvement of
      catecholaminergic neurotransmitters released in the ovary upon the combination of
      noradrenergic stimulation of the celiac ganglion and LH treatment of the ovary.
      METHODS: The ex vivo celiac ganglion-superior ovarian nerve-ovary integrated
      system was used. This model allows studying in vitro how direct neural
      connections from the celiac ganglion regulate ovarian steroidogenic output. The
      system was incubated in buffer solution with the ganglion and the ovary located
      in different compartments and linked by the superior ovarian nerve. Three
      experiments were designed with the addition of: 1) noradrenaline in the ganglion
      compartment; 2) LH in the ovarian compartment; and 3) noradrenaline and LH in the
      ganglion and ovarian compartments, respectively. Rats of 15, 19, 20 and 21 days
      of pregnancy were used, and, as an end point, the concentration of the
      luteotropic hormone androstenedione was measured in the ovarian compartment by
      RIA at various times of incubation. For some of the experimental paradigms the
      concentration of various catecholamines (dihydroxyphenylalanine, dopamine,
      noradrenaline and adrenaline) was also measured in the ovarian compartment by
      HPLC. RESULTS: The most relevant result concerning the action of noradrenaline in
      the celiac ganglion was found on day 21 of pregnancy resulting in the inhibition
      of androstenedione release from the ovarian compartment. In addition on day 15 of
      pregnancy, LH placed in the ovarian compartment led to an inhibition of the
      release of androstenedione, and this inhibitory effect was further reinforced by
      the joint action of noradrenaline in the celiac ganglion and LH in the ovary. The
      levels of catecholamines in the ovarian compartment showed differences among the
      experiments; of significance, the joint treatment of noradrenaline in the celiac
      ganglion and LH in the ovary resulted in a remarkable increase in the ovarian
      levels of noradrenaline and adrenaline when compared to the effect achieved by
      either one of the compounds added alone. CONCLUSION: Our results demonstrate that
      the noradrenergic stimulation of the celiac ganglion reinforces the LH-induced
      inhibition of androstenedione production by the ovary of late pregnant rats, and
      that this effect is associated with marked changes in the release of
      catecholamines in the ovary.

PMID- 17184552
TI  - Dental general anaesthetic trends among Australian children.
AB  - BACKGROUND: Children receive dental general anaesthetic (DGA) care when standard
      dental treatment is not possible. Receipt of DGA care is resource-intensive and
      not without risk. This study examines trends in receipt of DGA care among
      Australian children. METHODS: Child DGA data were obtained from the Australian
      Institute of Health and Welfare Hospital Morbidity Database for 1993-2004.
      Poisson regression modelling was used to examine DGA rates in relation to age,
      sex, Indigenous status, location, year and procedure. RESULTS: There was a 3-fold
      increase in DGA rates from 1993-1994 (215.8 +/- 2.9 per 100,000) to 2003-2004
      (731.4 +/- 5.3 per 100,000) (P < 0.001). Across all years, children who were aged
      0-4 years, male or rural/remote-dwelling had higher DGA rates than their 5-9-year
      old, female or metropolitan-dwelling counterparts respectively. There was a 7.0
      fold increase in the rate of Indigenous admissions from 1993-1994 (116.5 +/- 10.2
      per 100,000) to 2003-2004 (806.6 +/- 25.7 per 100,000). Extraction rates
      increased 4.9-fold from 1993-1994 (109.2 +/- 2.9 per 100,000) to 2003-2004 (540.0
      +/- 4.5 per 100,000), while restoration rates increased 3.3-fold in the same
      observation period (139.5 +/- 2.3 per 100,000 in 1993-1994 to 462.6 +/- 4.2 per
      100,000 in 2003-2004). For admissions in which one or more extractions were
      received, Indigenous rates were 47% greater than non-Indigenous rates after
      adjusting for other covariates. CONCLUSION: Child DGA rates in Australia are
      increasing. Children who are pre-school-aged, male, Indigenous or living in a
      rural/remote location are disproportionally represented among those receiving
      such care. There are higher rates of extractions as opposed to more conservative
      procedures, particularly among Indigenous children.

PMID- 17184553
TI  - Breastfeeding duration in mothers who express breast milk: a cohort study.
AB  - BACKGROUND: The expression of breast milk allows a mother to be away
      intermittently from her infant while continuing to breastfeed. The aim of this
      study was to investigate the association between expression of breast milk and
      breastfeeding duration METHODS: A cohort study of 12 months duration. The mothers
      were recruited from two public maternity hospitals in Perth, Australia between
      mid-September 2002 and mid-July 2003. While in hospital, participating mothers
      completed a questionnaire that included questions on how they were feeding their
      newborn. Telephone interviews conducted at regular periods monitored changes in
      infant feeding practices, including expression of breast milk. Multivariate Cox
      regression analysis was used to explore the association between breast milk
      expression and the duration of any breastfeeding. RESULTS: A total of 587
      mothers, or 55% of those eligible, participated in the study. Of these 93.5% were
      breastfeeding at discharge from hospital. Mothers who expressed breast milk (at
      one or more time periods) were less likely to discontinue any breastfeeding
      before six months (Relative Risk 0.71, 95% CI 0.52, 0.98) than those who had
      never expressed milk. CONCLUSION: This study found that mothers who express
      breast milk are more likely to breastfeed to six months (any breastfeeding).
      While further research is required in different cultures to confirm these
      results, the appropriate use of expressed breast milk may be a means to help
      mothers to achieve six months of full breastfeeding while giving more lifestyle
      options.

PMID- 17184554
TI  - Bench-to-bedside review: high-frequency oscillatory ventilation in adults with
      acute respiratory distress syndrome.
AB  - Mechanical ventilation is the cornerstone of therapy for patients with acute
      respiratory distress syndrome (ARDS). Paradoxically, mechanical ventilation can
      exacerbate lung damage--a phenomenon known as ventilator-induced lung injury.
      While new ventilation strategies have reduced the mortality rate in patients with
      ARDS, this mortality rate still remains high. High-frequency oscillatory
      ventilation (HFOV) is an unconventional form of ventilation that may improve
      oxygenation in patients with ARDS, while limiting further lung injury associated
      with high ventilatory pressures and volumes delivered during conventional
      ventilation. HFOV has been used for almost two decades in the neonatal
      population, but there is more limited experience with HFOV in the adult
      population. In adults, the majority of the published literature is in the form of
      small observational studies in which HFOV was used as 'rescue' therapy for
      patients with very severe ARDS who were failing conventional ventilation. Two
      prospective randomized controlled trials, however, while showing no mortality
      benefit, have suggested that HFOV, compared with conventional ventilation, is a
      safe and effective ventilation strategy for adults with ARDS. Several studies
      suggest that HFOV may improve outcomes if used early in the course of ARDS, or if
      used in certain populations. This review will summarize the evidence supporting
      the use of HFOV in adults with ARDS.

PMID- 17184555
TI  - Clinical review: management of difficult airways.
AB  - Difficulties or failure in airway management are still important factors in
      morbidity and mortality related to anesthesia and intensive care. A patent and
      secure airway is essential to manage anesthetized or critically ill patients.
      Oxygenation maintenance during tracheal intubation is the cornerstone of
      difficult airway management and is always emphasized in guidelines. The
      occurrence of respiratory adverse events has decreased in claims for injuries due
      to inadequate airway management mainly at induction of anesthesia. Nevertheless,
      claim reports emphasize that airway emergencies, tracheal extubation and/or
      recovery of anesthesia phases are still associated with death or brain damage,
      indicating that additional educational support and management strategies to
      improve patient safety are required. The present brief review analyses specific
      problems of airway management related to difficult tracheal intubation and to
      difficult mask ventilation prediction. The review will focus on basic airway
      management including preoxygenation, and on some oxygenation and tracheal
      intubation techniques that may be performed to solve a difficult airway.

PMID- 17184556
TI  - High-throughput genomic technology in research and clinical management of breast
      cancer. Plasma-based proteomics in early detection and therapy.
AB  - Protein-based breast cancer biomarkers are a promising resource for breast cancer
      detection at the earliest and most treatable stages of the disease. Plasma is
      well suited to proteomic-based methods of biomarker discovery because it is
      easily obtained, is routinely used in the diagnosis of many diseases, and has a
      rich proteome. However, due to the vast dynamic range in protein concentration
      and the often uncertain tissue and cellular origin of plasma proteins, proteomic
      analysis of plasma requires special consideration compared with tissue and
      cultured cells. This review briefly touches on the search for plasma-based
      protein biomarkers for the early detection and treatment of breast cancer.

PMID- 17184557
TI  - Should we use central venous saturation to guide management in high-risk surgical
      patients?
AB  - Measurements of central venous oxygen saturation (ScvO2) have been successfully
      used to guide haemodynamic therapy in critical care. The efficacy of this
      approach in the treatment of severe sepsis and septic shock has stimulated
      interest in the use of ScvO2 to guide management in patients undergoing major
      surgery. The physiological basis of ScvO2 measurement is complex. A number of
      outstanding issues will need to be resolved before incorporating ScvO2
      measurement into routine practice. First, it is not yet clear which value of
      ScvO2 should be targeted. Second, there is some uncertainty as to which
      interventions are the most effective for achieving the desired value of ScvO2 or
      how long this value should be maintained. The study by The Collaborative Study
      Group on Perioperative ScvO2 Monitoring published in this edition of Critical
      Care may help provide answers to some of these questions. Our understanding of
      ScvO2 measurement remains limited, however, and the routine use of peri-operative
      ScvO2-guided goal-directed therapy cannot be recommended until a large randomised
      trial has confirmed the value of this approach.

PMID- 17184558
TI  - Seleno-enzymes and seleno-compounds: the two faces of selenium.
AB  - Selenium protects cells and inhibits many inflammatory cell mechanisms through
      antioxidant seleno-enzymes. Immunity improvement is illustrated by the study of
      Berger and colleagues, with reduction of nosocomial pneumonia in burnt patients
      under multi-trace-element supplementation. As seleno-compounds (especially sodium
      selenite) are pro-oxidant, however, administration above 800 microg/day may be
      dangerous in septic shock. Paradoxically, direct reversible pro-oxidative effects
      of seleno-compounds may also be beneficial for reduction of inflammation (genomic
      action, apoptosis), and may even be bactericidal or virucidal. These facts need
      to be further examined, as well as the possible dramatic drop of plasma
      selenoprotein P in septic shock and its role in endothelium protection.

PMID- 17184559
TI  - A quantum leap in our knowledge of breast cancer mutations.

PMID- 17184560
TI  - Bench-to-bedside review: human subjects research--are more standards needed?
AB  - There are many controversial issues surrounding ethics in study design and
      conduct of human subjects research. In this review we briefly touch on the origin
      of ethics in clinical research and how the current regulations and standards came
      into practice. We then discuss current controversies regarding informed consent,
      conflicts of interest, institutional review boards, and other relevant issues
      such as innovative procedures and quality improvement projects. The question of
      whether we need more standards is a very important yet challenging one to which
      there is no simple answer. We address this question by reviewing and commenting
      on relevant literature. We conclude that what is needed are not more standards
      per se, but rather refinement and uniformity of current standards, and their
      interpretation and application both to protect human subjects and to advance
      medicine.

PMID- 17184561
TI  - Double-barrelled aorta with tetralogy of Fallot and pulmonary atresia.
AB  - We report the first case of double-barrelled aorta associated with tetralogy of
      Fallot and pulmonary atresia, and we discuss the difficulties in the terminology
      of this fascinating anomaly.

PMID- 17184562
TI  - Outcome after surgical repair of congenital cardiac malformations at school age.
AB  - OBJECTIVES: To explore the long-term physical, educational, behavioural, and
      emotional outcome of patients undergoing surgical correction of congenital
      cardiac disease at school age, and to investigate the relation, if any, between
      the outcome and comorbidity, age and sex, and level of complexity of the cardiac
      surgery. METHODS: Information was obtained concerning 101 patients who underwent
      open-heart surgery for correction of congenital cardiac malformations between
      1992 and 2000 whilst aged from 6 to 16 years. The patients, and their parents,
      completed the questionnaire "Outcome of congenital heart disease and surgery",
      the RAND 36-Item Health Survey, and the Child Behaviour Checklist/Youth Self
      Report/Young Adult Self-Report. RESULTS: Of the patients, 26% had comorbidity. Of
      those without comorbidity, 39% had frequent physical complaints, and 28%
      experienced limitations due to the cardiac disease. Nevertheless, the patients
      reported a good subjective state of health, and did not report any behavioural or
      emotional problems. Patients did show academic difficulties. They had received
      special education more frequently than their healthy peers, and many had needed
      to repeat a grade, or had received remedial teaching. Consequently, the
      educational level of patients was lower than that of their healthy peers.
      Patients with comorbidity, female patients, and patients who underwent complex
      surgery, seemed to be most at risk for physical, behavioural, and emotional
      problems. CONCLUSION: It is necessary to distinguish between physical state and
      its appraisal, and clinicians should be aware of this. Further research is needed
      to find out the cause and nature of the academic difficulties. Groups of patients
      at risk should be followed closely to enable early interventions.

PMID- 17184564
TI  - The case for utilizing more strict quantitative Doppler echocardiographic
      criterions for diagnosis of subclinical rheumatic carditis.
AB  - AIM: Our aim was to perform a comparative, quantitative and qualitative, analysis
      of valvar echocardiographic findings in patients with acute rheumatic fever, with
      or without clinical manifestations of carditis, as compared to healthy controls.
      METHODS AND RESULTS: We analyzed cross-sectional Doppler echocardiographic images
      of 31 patients with acute rheumatic fever diagnosed according to the Jones
      criterions as modified in 1992. Of 31 patients, 22 presented with clinical
      carditis, while 9 had subclinical carditis. The patients, and a control group of
      20 healthy individuals, underwent cardiac examination and echocardiographic
      assessment, assessing quantitative and qualitative findings of mitral and aortic
      valvar abnormalities. The leaflets of the mitral valve were statistically thicker
      in those with clinical and subclinical carditis when compared to controls (p less
      than 0.001). We observed a greater frequency of mitral variance, convergence of
      mitral flow, and aortic regurgitation for those with clinical and subclinical
      carditis when compared to controls (p less than 0.001, p less than 0.001 and p
      equal to 0.003, respectively). Patients with clinical and subclinical carditis
      had more quantitative and qualitative changes in the parameters than did the
      controls. CONCLUSION: Echocardiography is a sensitive method to detect valvar
      abnormalities in patients with acute rheumatic fever and carditis. Additionally,
      by using regular standardized criterions, abnormalities that lead to a diagnosis
      of subclinical carditis are found in those patients with acute rheumatic fever in
      the apparent absence of cardiac involvement.

PMID- 17184563
TI  - Severe aortic valvar stenosis in familial Noonan syndrome with mutation of the
      PTPN11 gene.
AB  - Noonan's syndrome is an autosomal dominant genetic disease, in which mutation of
      the PTPN11 gene is found in from one-third to half of all cases. Pulmonary valvar
      stenosis and myocardiopathy are frequently associated cardiac malformations,
      whereas aortic valvar stenosis is rarely described. We report, as far as we know,
      the first case of familial Noonan syndrome with severe aortic valvar stenosis,
      demonstrating mutation of the PTPN11 gene in the father of the patient.

PMID- 17184565
TI  - A comparison between the early and mid-term results of surgical as opposed to
      percutaneous closure of defects in the oval fossa in children aged less than 6
      years.
AB  - OBJECTIVES: To compare surgical as opposed to percutaneous interventional closure
      of isolated atrial septal defects in the oval fossa in terms of hospital stay,
      efficacy, and complications, and to study the respective role of the two
      techniques in current practice. METHODS: Between January 1998 and April 2004, 126
      out of 1210 patients treated at our institution for closure of an isolated defect
      in the oval fossa were aged less than 6 years. The mean age of these 126 patients
      at procedure was 4.2 plus or minus 1 year. The ratio of females to males was 74
      to 52. RESULTS: Of the patients, 62% were treated successfully using a
      percutaneous approach. The groups treated surgically or percutaneously did not
      differ for age, gender, or indications for treatment. No deaths occurred. The
      rates of total and major complications were higher in the group undergoing
      surgical closure, at 34% versus 9%, p less than 0.0001, and 10.5% versus 1%, p
      equal to 0.01, respectively. Embolisation of the device requiring subsequent
      surgery occurred in 1% of patients. The stay in hospital was shorter in those
      closed percutaneously, at 3.2 plus or minus 0.9 days versus 6.8 plus or minus 2.8
      days, p equal to 0.0001. During a mean follow-up of 3.4 plus or minus 1.9 years,
      no major complications occurred in either group, and symptoms improved
      significantly in both groups. Additional sequels occurred in 2 patients who had
      major complications subsequent to surgical closure. CONCLUSIONS: Even in young
      children, it is both feasible and safe to close defects in the oval fossa
      percutaneously. Compared to surgical closure, the transcatheter approach allows a
      shorter stay in hospital, and has a lower rate of complications. Early and mid
      term follow-up has confirmed the safety and efficacy of both techniques.

PMID- 17184566
TI  - Mitral valvar regurgitation in a child with Sweet's syndrome.
AB  - We report the very unusual perforation of the mitral valve in the setting of
      Sweet's syndrome, or acute febrile neutrophilic dermatosis, in a boy aged 5
      years. Surgical repair was uneventful, and follow-up showed no residual
      anomalies. Acute or delayed valvitis, with damage to either the mitral or aortic
      valves, should be screened for in this rare disease.

PMID- 17184567
TI  - Patency or recanalization of the arterial duct after surgical double ligation and
      transfixion.
AB  - OBJECTIVE: The frequency of residual shunting or recanalization was investigated
      in patients in whom a persistently patent arterial duct had been doubly ligated
      and transfixed during surgical closure. METHODS: We investigated in retrospective
      fashion for any residual shunting 325 patients who, between January 1990 and
      December 2004, had undergone surgical double ligation and transfixion of a
      persistently patent arterial duct. Shunting was discovered in 10 patients, of
      whom four male and six female. RESULTS: Of those with residual shunting. 4
      patients had initially exhibited only persistent patency of the duct, while the
      other 6 had associated mild cardiac lesions. The mean age at operation was 5.5
      years, with a range from 0.5 to 17.9 years. Postoperatively, the mean period for
      detecting the residual shunt was 22.8 months, with a range from 2 days to 72
      months. The frequency of residual shunting amongst our patients, therefore, was
      3.1%. We detected the residual shunt by colour-flow Doppler mapping in all
      patients, although a continuous murmur was heard in only one patient on physical
      examination. CONCLUSION: Our findings suggest that clinical sensitivity of
      detecting residual shunting subsequent to surgical closure of the persistently
      patent arterial duct is low, and hence that colour-flow Doppler interrogation
      should be a part of follow up. Residual shunting, or recanalization, may occur
      even after double ligation and transfixion of the duct. Since the residual flow
      may emerge after months, or even years, follow-up is needed for longer periods.

PMID- 17184568
TI  - Cardiac anomalies in the setting of the Abernethy malformation of the portal
      vein.
AB  - We describe a child with tricuspid atresia associated with a porto-systemic shunt
      and complete absence of the portal vein, the latter known as the Abernethy
      malformation. As far as we are aware, this association has not previously been
      reported. We review the various cardiac defects that have been reported in
      children with the Abernethy malformation, emphasizing the interesting clinical
      presentations of this rare malformation of the portal venous system.

PMID- 17184569
TI  - Angiographic diagnosis, prevalence and outcomes for left ventricular
      noncompaction in children with congenital cardiac disease.
AB  - Little is known about the implications of left ventricular noncompaction in
      children with additional congenital cardiac malformations. With this in mind, we
      conducted a retrospective review of every left ventricular angiogram performed in
      a single tertiary referral centre for paediatric cardiology, in Melbourne,
      Australia, between 1994 and 2000 in children with congenital heart disease,
      looking specifically for patients with angiographic evidence of noncompaction of
      the left ventricle. The outcome of patients identified as having noncompaction
      was compared with that of patients from the same population, stratified by their
      primary congenital cardiac malformation. Of 1515 children undergoing left
      ventricular angiography, 31, with 13 being male, were found to have angiographic
      evidence of left ventricular noncompaction, giving a prevalence of 2% (95% CI:
      1.3%-2.8%). Of 69 (22%) children with a functionally single left ventricle, 15
      fulfilled the criterions for noncompaction, compared to 16 of 1446 (1.1%)
      children with a balanced ventricular arrangement (p is less than 0.0001). The
      presence of noncompaction and a functionally single left ventricle were each
      associated with a doubling of mortality, the effect being cumulative. Of
      surviving patients with left ventricular noncompaction, 19% (4%-34%) have left
      ventricular dysfunction at their latest follow-up. We suggest that the important
      late sequels of noncompaction justify careful scrutiny for this entity in
      children with congenital cardiac disease.

PMID- 17184570
TI  - What is anatomically corrected malposition?

PMID- 17184571
TI  - Isolated obstruction of the right ventricular infundibulum in a patient with
      Williams' syndrome.
AB  - Williams' syndrome is a rare condition that is associated with severe
      cardiovascular manifestations. We report a patient with Williams' syndrome who
      also has isolated obstruction of the right ventricular infundibulum, an
      association that, to the best of our knowledge, has not been previously reported.

PMID- 17184572
TI  - An extensive long term follow-up of a cohort of patients with hypoplasia of the
      left heart.
AB  - We report the results of follow-up of the complete cohort of Norwegian children
      born in the period from 1987 through 1998 in whom there was the intention to
      treat surgically hypoplasia of the left heart using the Norwood sequence of
      operations. Of the 54 children, 21 are alive. Of these, 15 have been extensively
      studied, while the medical state of all the remaining survivors is known from
      reports from other hospitals. Of the survivors, the majority have reasonably
      acceptable cardiac and haemodynamic function, but significant neurological and
      neuropsychological morbidity is identified within the group as a whole, which
      requires special attention from qualified personnel of various kinds.

PMID- 17184573
TI  - Low-dose oral sildenafil for patients with pulmonary hypertension: a cost
      effective solution in countries with limited resources.
AB  - INTRODUCTION: Pulmonary arterial hypertension, both primary and secondary,
      continues to pose a therapeutic problem. In this study, we evaluate the efficacy
      and safety of a low-dose of oral sildenafil in 10 patients with pulmonary
      arterial hypertension. METHODS: We administered a single daily dose of 0.5
      milligrams per kilogram of sildenafil for 3 months to 10 patients with pulmonary
      arterial hypertension. Their average age was 26.8 years. Diagnoses were primary
      pulmonary arterial hypertension in 3 patients, and secondary pulmonary arterial
      hypertension due to congenital cardiac disease in the remaining 7 patients.
      Outcome measures included the clinical state, the mean pulmonary arterial
      pressure, and the indexed pulmonary vascular resistance; the latter two assessed
      at the beginning and at the end of the treatment period by cardiac
      catheterization. We also analysed the cost of the treatment. RESULTS: Oral
      treatment was well tolerated, and resulted in an improvement of the functional
      capacity in 9 of the 10 patients. Pulmonary arterial pressure decreased from 70
      to 60 millimetres of mercury (p equal to 0.05), and indexed pulmonary vascular
      resistance decreased from 21.8 to 15.8 Wood units per square metre (p equal to
      0.006). The mean cost per patient for 3 months on oral treatment with sildenafil
      was 120.99 American dollars. CONCLUSIONS: A low dose of 0.5 milligrams per
      kilogram per day of oral sildenafil, instead of 1 to 4 milligrams per kilogram
      per day, provided early clinical and haemodynamic improvements, and proved less
      expensive. Additional experience is now required to define more reliably the true
      long-term benefits of this therapy.

PMID- 17184574
TI  - Intra-aortic balloon counterpulsation in a patient with the failing Fontan
      circulation.
AB  - We report a 23-year-old patient undergoing functionally univentricular repair who
      developed cardiac failure due primarily to systemic ventricular dysfunction. The
      failing Fontan circulation was successfully re-established using intra-aortic
      balloon counterpulsation. Aortic counterpulsation facilitates recovery of
      systemic ventricular function, and appears to be a reasonable alternative in
      select instances of cardiac failure in patients with the Fontan circulation.

PMID- 17184575
TI  - Novel point mutation in the NKX2-5 gene in a Moroccan family with
      atrioventricular conduction disturbance and an atrial septal defect in the oval
      fossa.
AB  - Defects of the oval fossa usually occur as isolated malformations, but can show
      an autosomal dominant pedigree in familial cases. Several mutations have been
      described for the transcription factor NKX2-5, and co-segregate with varied
      cardiac anomalies. We have identified by sequence analysis a novel missense
      heterozygous mutation in the NKX2-5 gene, specifically a substitution of
      glutamine for proline at codon 160, in a Moroccan family, the affected members
      having a deficiency of the floor of the oval fossa and atrioventricular block.

PMID- 17184576
TI  - Exploring in vitro roles of siRNA in cardiovascular disease.
AB  - RNA interference (RNAi) is an adaptive defense mechanism through which double
      stranded RNAs silence cognate genes in a sequence-specific manner. It has been
      employed widely as a powerful tool in functional genomics studies, target
      validation and therapeutic product development. Similarly, the application of
      small interfering RNA (siRNA) to the silencing of the disease-causing genes
      involved in cardiovascular diseases has made great progress. In this overview, we
      attempt to provide a brief outline of the current understanding of the mechanism
      of RNAi and its potential application to the cardiovascular system, with
      particular emphasis on its ability to identify the pathophysiological function of
      genes related to several important cardiovascular disorders. The prospects of
      RNAi-based therapeutics, as well as the advantages and potential problems, are
      also discussed.

PMID- 17184577
TI  - Endogenous histamine inhibits the development of morphine-induced conditioned
      place preference.
AB  - AIM: The conditioned place preference (CPP) paradigm was used to investigate the
      effects of endogenous histamine on the processes leading to morphine-induced
      reward-seeking behavior in Sprague-Dawley rats. METHODS: The model of CPP was
      used to assess the rewarding effect of morphine. The levels of histamine,
      glutamate, gamma-aminobutyric acid (GABA), dopamine (DA) and 3, 4
      dihydroxyphenylacetic acid (DOPAC) in rat brains were measured with high
      performance liquid chromatography. Immunohistochemistry technique was used to
      observe the morphological changes of neurons. RESULTS: Intraperitoneal injection
      of morphine (2, 5 or 10 mg/kg) induced the development of CPP in a dose-dependent
      manner. In addition, morphine administrations (10 mg/kg) decreased the histamine
      content and reduced the number and size of histaminergic neurons in the tubero
      mammillary nucleus (TM), as well as markedly increasing the DOPAC/DA ratios in
      the ventral tegmental area (VTA) and nucleus accumbens (NAc). Intraperitoneal
      injection of histidine (50, 100 or 200 mg/kg) dose-dependently inhibited the
      development of morphine-induced CPP. Bilateral lesions of the TM, which decreased
      the histamine levels in the VTA and NAc, potentiated the development of CPP
      induced by morphine (1 mg/kg, a dose that produced no appreciable effect when
      given alone) and increased the DOPAC/DA ratios in the VTA and NAc, but did not
      change the glutamate or GABA levels in these nuclei. Histidine reversed the
      effects of the TM lesions. CONCLUSION: These results indicate that endogenous
      histamine plays a role in inhibiting the development of morphine-induced reward
      seeking behavior, and the inhibition may involve the modulation of dopaminergic
      activity.

PMID- 17184578
TI  - Neuroprotection of selenite against ischemic brain injury through negatively
      regulating early activation of ASK1/JNK cascade via activation of PI3K/AKT
      pathway.
AB  - AIM: To investigate whether selenite, a known antioxidant, could decrease the
      activation of apoptosis signal regulating kinase 1/c-jun N-terminal kinase (ASK1/
      JNK) signaling cascade in cerebral ischemia/reperfusion (I/R) by activating the
      phosphatidylinositol 3-kinase (PI3K)/AKT pathway in rat hippocampi, and the
      neuroprotective effect of selenite against ischemic injury after 15 min of
      transient brain ischemia. METHODS: Transient global brain ischemia was induced by
      4-vessel occlusion into adult male Sprague-Dawley rats weighing 250-300 g. The
      rats were pretreated only with selenite (0.3 mg/kg dissolved in 0.9% saline)
      every 24 h for 7 d by means of intravenous injection of the tail or combined with
      LY294002 from d 5 by left cerebral ventricle injection before surgery. RESULTS:
      Selenite significantly increased AKT1 activation and decreased the activation of
      ASK1/ JNK cascade via phosphorylating ASK1 at Ser-83 residue by AKT1 during early
      reperfusion after 15 min transient global brain ischemia. On the contrary,
      combined pretreatment of the rats with LY294002 (a specific PI3K inhibitor) and
      selenite significantly inhibited the effects solely with selenite. CONCLUSION:
      The activation of the pro-apoptotic ASK1/JNK cascade, which is closely associated
      with oxidative stress, could be suppressed by selenite through activating the
      antiapoptotic PI3K/AKT pathway during early reperfusion after cerebral ischemia
      in rat hippocampi.

PMID- 17184579
TI  - Nitric oxide modulates hypoxic pulmonary smooth muscle cell proliferation and
      apoptosis by regulating carbon monoxide pathway.
AB  - AIM: To explore the role of carbon monoxide (CO) in the regulation of hypoxic
      pulmonary artery smooth muscle cell (PASMC) proliferation and apoptosis by nitric
      oxide (NO). METHODS: PASMC of Wistar rats was cultured in vitro in the presence
      of a NO donor, sodium nitroprusside, or an inhibitor of heme oxygenase (HO), zinc
      protoporphyrin-IX, or under both normoxic and hypoxic conditions. Nitrite and
      carboxyhemoglobin in PASMC medium were detected with spectrophotometry. The
      proliferating and apoptotic percentage of PASMC was measured by flow cytometry.
      The expression of HO-1 mRNA in PASMC was analyzed by fluorescent real-time
      quantitative PCR, and the proliferating cell nuclear antigen and caspase-3 were
      examined by immunocytochemical analysis. RESULTS: The results showed that hypoxia
      suppressed NO generation from PASMC, which promoted hypoxic PASMC proliferation
      and induced apoptosis. Meanwhile, hypoxia induced HO-1 expression in PASMC and
      promoted CO production from PASMC, which inhibited PASMC proliferation and
      regulated PASMC apoptosis. NO upregulated the expression of HO-1 mRNA in hypoxic
      PASMC; NO also inhibited proliferation and promoted apoptosis of hypoxic PASMC,
      possibly by regulating the production of CO. CONCLUSION: The results indicated
      that CO could inhibit proliferation and regulate apoptosis of PASMC, and NO
      inhibited proliferation and promoted apoptosis of hypoxic PASMC, possibly by
      regulating the production of CO.

PMID- 17184580
TI  - Urotensin II accelerates cardiac fibrosis and hypertrophy of rats induced by
      isoproterenol.
AB  - AIM: To study whether urotensin II (UII), a potent vasoconstrictive peptide, is
      involved in the development of cardiac hypertrophy and fibrogenesis of rats
      induced by isoproterenol (ISO). METHODS: Thirty male Wistar rats were randomly
      divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO
      group, and group 3 was the ISO+UII group. In groups 2 and 3, ISO (5 mg x kg(-1) x
      d(-1)) was given (sc) once daily for 7 d. Group 3 was also given UII in the first
      day [3 nmol/kg (5 microg/kg), iv], followed by sc (1.5 microg/kg) twice daily.
      Group 1 received 0.9% saline. UII receptor (UT) mRNA expression was determined by
      RT-PCR. The contents of UII and angiotensin II (Ang II) were determined by
      radioimmunoassay. In vitro, the effects of UII on DNA/collagen synthesis of
      cardiac fibroblasts were determined by [3H]thymidine/[3H]proline incorporation.
      RESULTS: The ratio of heart weight/body weight, plasma lactate dehydrogenase
      activity, myocardial malondialdehyde and hydroxyproline concentration increased
      significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac
      UII and ventricular Ang II, compared with the control group (P< 0.01). ISO
      induced significant myocardial fibrogenesis. Moreover, UII+ISO co-treatment
      significantly increased the changes of biochemical markers of injury and the
      degree of cardiac hypertrophy and fibrosis. In vitro, 5 x 10(-9 )-5 x 10(-7 )
      mol/L UII stimulated [3H]thymidine/[3H] proline incorporation into cardiac
      fibroblasts in a dose-dependent manner (P< 0.01). CONCLUSION: These results
      suggest that UII was involved in the development of cardiac fibrosis and
      hypertrophy by synergistic effects with ISO.

PMID- 17184582
TI  - Cardioprotective effects of diltiazem reevaluated by a novel myocardial ischemic
      model in Chinese miniature swine.
AB  - AIM: To develop a new model of myocardial ischemia in Chinese miniature swine and
      reevaluate the cardioprotective effects of diltiazem. METHODS: Myocardial
      ischemia was induced by injecting self-embolus into the left anterior descending
      (LAD) coronary artery in qualified miniature swine. Diltiazem (5 mg. kg(-1). d(
      1)) was orally administered to the swine by mixing into normal pig diet from 1 to
      6 d after self-embolus injection. The coronary angiography, 30 point body surface
      electrocardiogram (BS-ECG), hemodynamics, biochemistry, quantitative histology
      and pathohistology were determined 6 d after self-embolus injection. RESULTS:
      Embolization occurred in the LAD coronary artery of the Chinese miniature swine
      injected by self-embolus. There were significant myocardial ischemia and large
      cardiac muscle infarction in the Chinese miniature swine, which were accompanied
      with increased BS-ECG, decreased hemodynamic indexes of the cardiac output,
      cardiac index, left cardiac work and left cardiac work index, and increased
      systemic vascular resistance index. Pathohistological analysis revealed
      myocardial degeneration, necrosis, fibrosis, inflammatory cell infiltration and
      granulation tissue hyperblastosis (n=6). Diltiazem diminished the extent of the
      LAD embolism, ameliorated myocardial ischemia, improved the hemodynamic indexes,
      increased the plasma superoxide dismutase activity, decreased the plasma
      malondialdehyde content, narrowed the myocardial ischemic area and weakened the
      pathohistological damage in the cardiac muscle (n=6). CONCLUSION: Myocardial
      ischemia induced by injecting self-embolus into the LAD coronary artery in
      Chinese miniature swine is quite close to clinical pathophysiological conditions.
      Diltiazem is effective to inhibit the myocardial ischemia and restore the heart
      function in this novel model.

PMID- 17184581
TI  - Hypoxia reoxygenation induces premature senescence in neonatal SD rat
      cardiomyocytes.
AB  - AIM: To investigate whether hypoxia reoxygenation induces premature senescence in
      neonatal Sprague-Dawley (SD) rat cardiomyocytes. METHODS: Cardiomyocytes were
      isolated from neonatal SD rat heart and identified by immunohistochemistry. The
      control cultures were incubated at 37 degree centigrade in a humidified
      atmosphere of 5% CO(2) and 95% air. The hypoxic cultures were incubated in a
      modular incubator chamber filled with 1% O(2), 5% CO(2), and balance N2 for 6 h.
      The reoxygenated cultures were subjected to 1% O(2) and 5% CO(2) for 6 h, then
      21% oxygen for 4, 8, 12, 24, and 48 h, respectively. Cell proliferation was
      determined using bromodeoxyuridine labeling. The ultrastructure of cardiomyocytes
      was observed by using an electron microscope. beta-Galactosidase activity was
      determined by using a senescence beta-galactosidase Staining Kit. p16( INK4a )
      and telomerase reverse transcriptase (TERT) mRNA levels were measured by real
      time quantitative PCR. TERT protein expression was determined by
      immunohistochemistry. Telomerase activities were assayed by using the Telo TAGGG
      Telomerase PCR ELISAplus kit. RESULTS: The initial cultures consisted of pure
      cardiomyocytes identified by immunohistochemistry. The proportion of BrdU
      positive cells was reduced significantly in the hypoxia reoxygenation-treated
      group (P< 0.01). Under the condition of hypoxia reoxygenation, mitochondrial
      dehydration appeared; p16( INK4a ) and TERT mRNA levels, beta-galactosidase
      activity, TERT protein expression and telomerase activities were all
      significantly increased (P< 0.01 or P< 0.05). CONCLUSION: These data indicate
      that premature senescence could be induced in neonatal SD rat cardiomyocytes
      exposed to hypoxia reoxygenation. Although TERT significantly increased, it could
      not block senescence.

PMID- 17184583
TI  - Thrombolytic efficacy of native recombinant staphylokinase on femoral artery
      thrombus of rabbits.
AB  - AIM: To investigate the thrombolytic efficacy, ideal dosage and administration of
      native recombinant staphylokinase (r-SAK). METHODS: Forty New Zealand rabbits
      were randomly assigned into the control, r-SAK low-dose, medial-dose, high dose,
      single bolus, allied therapy, recombinant streptokinase (r-SK) and urokinase (UK)
      groups. The right femoral artery thrombosis models were made by balloon injury,
      and 120 min after the injury, the thrombolytic agents were infused through the
      rabbits' parallel-ear vein. RESULTS: (1) 2 h after balloon injury, the pulse
      pressures of the right femoral arteries reduced to 0 or less than 10% of that of
      left femoral arteries in all groups; (2) after thrombolytic therapy, the pulse
      pressures in some of the femoral arteries markedly enhanced to more than 50% of
      that of left femoral arteries; (3) the reopening rates in the r-SAK medial and
      high dose groups were significantly higher than that of the control. The
      reopening rate of the same dose native r-SAK was significant higher than that of
      UK and r-SK; (4) the patency score of the right femoral arteries tended to be
      better in the r-SAK medial and high-dose groups than that of the low-dose group,
      and the time to reopening in the allied therapy group tended to be shorter.
      CONCLUSION: (1) r-SAK has a definite thrombolytic effect on the femoral artery
      thrombus of rabbits; (2) single bolus is an effective manner of r-SAK therapy,
      and r-SAK allied therapy with heparin may shorten the time to recanalization; (3)
      the efficacy of the same dose native r-SAK was superior to that of r-SK and UK.

PMID- 17184584
TI  - CD151 gene delivery increases eNOS activity and induces ECV304 migration,
      proliferation and tube formation.
AB  - AIM: To investigate the effects of CD151 on the activity of endothelial NO
      synthase (eNOS), and ECV304 migration, proliferation and tube formation. METHODS:
      pAAV-CD151 and pAAV-anti-CD151 were constructed and used to transiently transfect
      ECV304 mediated with Lipofectamine 2000. After transfection, the expression of
      CD151 was measured by Western blotting. Cell migration assay was performed using
      Boyden transwell; proliferation assay was evaluated using the 3- [4,5
      dimethylthiazol-2-yl]-2,5, diphenyltetrazolium bromide (MTT) method, and tube
      formation test was examined on matrigel. eNOS activity was assayed by L-
      [3H]citrulline production from L-[3H]arginine. The involvement of eNOS was
      explored using an eNOS inhibitor (L-NAME) and the effects in the process were
      observed. RESULTS: CD151 promotes cell migration, proliferation and tube
      formation. In addition, CD151 increases eNOS activity. Moreover, cell migration,
      proliferation and tube formation induced by CD151 are inhibited when L-NAME is
      used, which indicates that there is an involvement of eNOS in CD151-induced cell
      migration, cell proliferation and tube formation. CONCLUSION: CD151 promotes
      ECV304 migration, proliferation and tube formation. The mechanism is that CD151
      increases eNOS activity. This result also suggests that eNOS is involved in the
      angiogenic effects of CD151.

PMID- 17184585
TI  - Serum amyloid A induces WISH cell apoptosis.
AB  - AIM: Serum amyloid A (SAA) is an important mammalian acute reactant. Here, we aim
      to investigate the effect of SAA on apoptosis and its mechanism of action in
      human amniotic WISH cells. METHODS: The expression of formyl peptide receptor
      (FPRL1), which is reported as a SAA receptor, was tested using RT-PCR and ligand
      binding assay with radio-labeled FPRL1 ligand. The effect of SAA on proliferating
      cell population was evaluated by thymidine incorporation assay. The protein
      phosphorylation levels and caspase-3 activity were detected by Western blot
      assay. RESULTS: SAA inhibits thymidine incorporation in human amniotic WISH
      cells. A SAA-induced decrease of proliferating cell population was accompanied
      with nuclear condensation and caspase-3 activation in WISH cells, suggesting that
      SAA induces WISH cell apoptosis. Since FPRL1 has been reported as a SAA receptor,
      we investigated the effects of several FRPL1 agonists on a proliferating cell
      population in WISH cells. Among the tested FPRL1 agonists, only SAA induced a
      decrease of proliferating cell population in WISH cells. On the downstream
      signaling of SAA, we found that SAA stimulated extracellular signal-regulated
      kinase and p38 kinase, which were not inhibited by pertussis toxin (PTX), ruling
      out the role of PTX-sensitive G-proteins. Furthermore a SAAinduced decrease of
      proliferating cell population was not affected by PTX, suggesting that SAA
      inhibits WISH cell apoptosis in a PTX-sensitive G-proteinindependent manner. A
      SAA-induced decrease of a proliferating cell population was completely blocked by
      PD98059 and SB203580, suggesting that mitogenactivated protein kinase activities
      are essentially required for the process. CONCLUSION: SAA is a novel inducer for
      WISH cell apoptosis, and the PTX-insensitive pathway is involved in the process.

PMID- 17184586
TI  - Triptolide suppresses IL-1beta-induced chemokine and stromelysin-1 gene
      expression in human colonic subepithelial myofibroblasts.
AB  - AIM: To examine the inhibitive effects of triptolide on the expression of IL-8,
      monocyte chemotactic protein (MCP)-1, and matrix metalloproteinases (MMP)-3 in
      subepithelial myofibroblasts (SEMF) stimulated with IL-1beta. METHODS: SEMF
      cultures were established from normal colons in patients who underwent gut
      resection for colorectal carcinoma. Chemokine and MMP-3 expressions were
      determined by ELISA and RT-PCR. The cytosolic amount of phosphorylation of I
      kappa B-alpha(p-I kappa B-alpha) was determined by Western blotting. The DNA
      binding capacity of NF-kappa B was evaluated by electrophoretic mobility shift
      assays. RESULTS: IL-1beta stimulated protein and mRNA expression of IL-8, MCP-1,
      and MMP-3 in SEMF. Triptolide inhibited these effects of IL-1beta in a dose
      dependent manner. Mechanistic studies revealed that triptolide markedly decreased
      IL-1beta -induced NF-kappa B DNA binding capacity and cytosolic amount of p-I
      kappa B-alpha. These results showed that triptolide inhibited IL-1beta -induced
      chemokine and MMP-3 expression in SEMF through the NF-kappa B pathway.
      CONCLUSION: Triptolide inhibited IL-1beta -induced chemokine and MMP-3 expression
      in SEMF by preventing the phosphorylation of I kappa B-alpha.

PMID- 17184587
TI  - Prevention of diabetic microangiopathy by prophylactic transplant of mobilized
      peripheral blood mononuclear cells.
AB  - AIM: To investigate whether the prophylactic local delivery of mobilized
      peripheral blood mononuclear cells (M-PBMNC) could prevent peripheral
      microangiopathy in diabetic nude mice. METHODS: Diabetic nude mice were induced
      with intraperitoneal injections of streptozotocin. With the time course of
      diabetes, we detected the capillary and arteriole density of mice adductor
      muscles by immunohistopathy. In situ apoptosis was detected by using TdT-mediated
      dUTP nick end labeling (TUNEL) methods. M-PBMNC were labeled and locally
      delivered to the adductor muscles. Mononuclear cells were also isolated and
      cultured in vitro for the detection and counting of endothelial progenitor
      cells(EPC). RESULTS: Rarefication of capillaries and arterioles, enhanced
      apoptosis in adductor muscles, and reduced circulating EPC in diabetic nude mice.
      Prophylactic local delivery of M-PBMNC halted the progression of microvascular
      rarefaction in hind-limb skeletal muscles by inhibiting apoptosis. We detected
      the survival, migration and incorporation of transplanted M-PBMNC into the murine
      vasculature in vivo. In addition, more EPC were available from M-PBMNC than non
      mobilized cells. CONCLUSION: These results suggested that the prophylactic local
      delivery of M-PBMNC may represent a novel approach for the treatment of
      microvascular complications in diabetics.

PMID- 17184588
TI  - Immune tolerance induced by adoptive transfer of dendritic cells in an insulin
      dependent diabetes mellitus murine model.
AB  - AIM: To investigate the effect and underlying mechanisms of immune-tolerance
      induced by the adoptive transfer of bone marrow (BM)-derived dendritic cells (DC)
      in insulin-dependent diabetes mellitus (IDDM) mice. METHODS: The IDDM model was
      established by a low dose of streptozotocin (STZ) in Balb/c mice. Two DC
      subpopulations were generated from the BM cells with granulocyte-macrophage
      colony-stimulating factor with or without interleukin-4. The purity and the T
      cell stimulatory capability of DC were identified. These cells were used to
      modulate autoimmune response in pre-diabetic mice. Blood glucose was examined
      weekly; pancreas tissues were taken for histopathological analysis, and CD4(+) T
      cells were isolated to detect lymphocyte proliferation by MTT assay and the ratio
      of CD4(+)CD25(+) T cells by fluorescence-activated cell sorting (FACS). The
      cytokine secretion was determined by ELISA analysis. RESULTS: Two DC subsets were
      generated from BM, which have phenotypes of mature DC (mDC) and immature DC
      (iDC), respectively. The level of blood glucose decreased significantly by
      transferring iDC (P< 0.01) rather than mDC. Less lymphocyte infiltration was
      observed in the islets, and pancreatic structure was intact. In vitro,
      proliferation of lymphocytes decreased and the proportion of CD4(+)CD25(+) T
      cells increased remarkably, compared with the mDC-treated groups (P< 0.05), which
      were associated with increased level of the Th2 cytokine and reduced level of the
      Th1 cytokine after iDC transfer. CONCLUSION: Our data showed that iDC transfer
      was able to confer protection to mice from STZ-induced IDDM. The immune-tolerance
      to IDDM may be associated with promoting the production of CD4(+)CD25(+) T cells
      and inducing regulatory Th2 responses in vivo.

PMID- 17184589
TI  - Curcumin synergistically augments bcr/abl phosphorothioate antisense
      oligonucleotides to inhibit growth of chronic myelogenous leukemia cells.
AB  - AIM: To investigate the growth inhibition effect of the combination of bcr/abl
      phosphorothioate antisense oligonucleotides (PS-ASODN) and curcumin (cur), and
      the possible mechanisms of cur on the chronic myelogenous leukemia cell line
      K562. METHODS: The K562 cell line was used as a P210( bcr/abl )-positive cell
      model in vitro and was exposed to different concentrations of PS-ASODN (0-20
      micromol/L), cur (0-20 micromol/L), or a combination of both. Growth inhibition
      and apoptosis of K562 cells were assessed by MTT assay and AO/EB fluorescent
      staining, respectively. The expression levels of P210( bcr/abl ), NF-kappaB and
      heat shock protein 90 (Hsp90) were assessed by Western blot. RESULTS: Exposure to
      cur (5-20 micromol/L) and PSASODN (5-20 micromol/L) resulted in a synergistic
      inhibitory effect on cell growth. Growth inhibition was associated with the
      inhibition of the proliferation and induction of apoptosis. Western blot analysis
      showed that the drugs synergistically downregulated the level of P210( bcr/abl )
      and NF-kappaB. Cur downregulated Hsp90, whereas no synergism was observed when
      cur was combined with PS-ASODN. CONCLUSION: PS-ASODN and cur exhibited a
      synergistic inhibitory effect on the cell growth of K562. The synergistic growth
      inhibition was mediated through different mechanisms that involved the inhibition
      of P210( bcr/abl ).

PMID- 17184590
TI  - Application of EGFP-EGF fusions to explore mechanism of endocytosis of epidermal
      growth factor.
AB  - AIM: To develop a simple method for monitoring protein localization of epidermal
      growth factor (EGF) in living cells. METHODS: Enhanced green fluorescent protein
      (EGFP) was used as an autofluorescent tag to label EGF ligands. SDS-PAGE and
      Western blot analysis were used to detect the expression of the EGFP-tagged EGF
      (EGFP-EGF) protein. The cell-binding and internalization activity of EGFP-EGF
      were analyzed by fluorescence-activated cell sorting (FACS) and confocal
      microscopy. RESULTS: EGFP-EGF protein was expressed in Escherichia coli and
      purified. A cell-binding assay demonstrated that the EGFP-EGF protein could bind
      efficiently to the cells expressing EGFR. The binding and internalization of EGFP
      EGF can be visualized even at a very low concentration under confocal microscopy.
      The FACS-based assay for internalization activity indicated the accumulation of
      internalized EGFP-EGF over time. Furthermore, the results of the competition
      assay indicated its EGFR binding specificity. Using such a method, it does not
      need to label EGF with chemicals and avoid light in the experimental process.
      CONCLUSION: The fusion protein EGFP-EGF has several characters including high
      sensitivity, stability and convenience for manipulation, and is a powerful tool
      for the study of EGF endocytosis.

PMID- 17184591
TI  - CYP3A4 mediated in vitro metabolism of vinflunine in human liver microsomes.
AB  - AIM: To study the metabolism of vinflunine and the effects of selective
      cytochrome P-450 (CYP450) inhibitors on the metabolism of vinflunine in human
      liver microsomes. METHODS: Individual selective CYP450 inhibitors were used to
      investigate their effects on the metabolism of vinflunine and the principal
      CYP450 isoform involved in the formation of metabolites M(1) and M(2) in human
      liver microsomes. RESULTS: Vinflunine was rapidly metabolized to 2 metabolites:
      M(1) and M(2) in human liver microsomes. M(1) and M(2) were tentatively presumed
      to be the N-oxide metabolite or hydroxylated metabolite and epoxide metabolite of
      vinflunine, respectively. Ketoconazole uncompetitively inhibited the formation of
      M(1), and competitively inhibited the formation of M(2), while alpha
      naphthoflavone, sulfaphenazole, diethyl dithiocarbamate, tranylcypromine and
      quinidine had little or no inhibitory effect on the formation of M(1) and M(2).
      CONCLUSION: Vinflunine is rapidly metabolized in human liver microsomes, and
      CYP3A4 is the major human CYP450 involved in the metabolism of vinflunine.

PMID- 17184592
TI  - Development of a homogeneous calcium mobilization assay for high throughput
      screening of mas-related gene receptor agonists.
AB  - AIM: To develop homogeneous calcium mobilization assay for high-throughput
      screening (HTS) of mas-related gene (Mrg) receptor agonists. METHODS: CHO-K1
      cells stably expressing the full-length MrgD receptor and a calcium-sensitive dye
      were used to develop an HTS assay based on intracellular calcium influx. This
      method was applied to large-scale screening of a library containing 8000
      synthetic compounds and natural product extracts. cAMP measurements were carried
      out to verify the bioactivities of the hits found by the calcium mobilization
      assay. Similar approaches were also employed in the identification of the MrgA1
      receptor agonists following HTS of 16,000 samples. RESULTS: EC(50) values of the
      positive control compounds (beta-alanine for MrgD receptor and dynorphin A for
      MrgA1 receptor) determined by the calcium mobilization assay were consistent with
      those reported in the literature, and the Z' factors were 0.65 and 0.50 for MrgD
      and MrgA1 receptor assay, respectively. About 31 compounds for the MrgD receptor
      and 48 compounds for the MrgA1 receptor showing > or =20% of the maximal agonist
      activities found in the controls were initially identified as hits. Secondary
      screening confirmed that 2 compounds for each receptor possessed specific agonist
      activities. Intracellular cAMP level measurements indicated that the 2 confirmed
      hits displayed the functionality of the MrgD receptor agonists. CONCLUSION: A
      series of validation studies demonstrated that the homogeneous calcium
      mobilization assay developed was highly efficient, amenable to automation and a
      robust tool to screen potential MrgD and MrgA1 receptor agonists. Its application
      may be expanded to other G-protein coupled receptors that mobilize calcium influx
      upon activation.

PMID- 17184593
TI  - Identification of human dopamine receptors agonists from Chinese herbs.
AB  - AIM: To find human dopamine receptors, especially D1-like receptor specific
      agonists from Chinese herbs as potential antihypertension drug leads. METHODS:
      Two D1-like receptor cell lines carrying a beta-lactamase reporter gene, and a D2
      receptor cell line coexpressing a promiscuous G protein G15 were constructed
      using HEK293 cells. A natural compound library made from fractionated samples of
      herbal extracts was used for high-throughput screening (HTS) against one of the
      cell lines, HEK/D5R/CRE-blax. The interested hits were evaluated for their
      activities against various dopamine receptors. RESULTS: Fourteen hits were
      identified from primary screening, of which 2 of the better hit samples, HD0522
      and HD0059, were selected for further material and activity analysis, and to
      obtain 2 compounds that appeared as 2 single peaks in HPLC, HD0522H01 and
      HD0059H01. HD0059H01 could activate D1, D2, and D5 receptors, with EC(50 ) values
      of 2.28 microg/mL, 0.85 microg/mL, and 1.41 microg/mL, respectively. HD0522H01
      could only activate D1R and D5R with EC(50 ) values of 2.95 microg/mL and 8.38
      microg/mL. CONCLUSION: We established cellbased assays for 3 different human
      dopamine receptors and identified specific agonists HD0522H01 and HD0059H01
      through HTS. The specific agonist to D1-like receptors, HD0522H01, may become a
      new natural product-based drug lead for antihypertension treatment.

PMID- 17184594
TI  - Design, synthesis, antitumor evaluations and molecular modeling studies of novel
      3,5-substituted indolin-2-one derivatives.
AB  - AIM: To design and synthesize a novel class of antitumor agents, featuring the 3,
      5-substituted indolin-2-one framework. METHODS: Based on enzyme binding features
      of (Z)-SU5402, introducing a beta-pyrrole group at the 3-position of the indolin-
      2-one core, a series of novel 3,5-substituted indolin-2-ones were designed and
      synthesized. Four human carcinoma cell lines of A-431, A-549, MDA-MB-468, and
      Autosomal Dominant Polycystic Kidney disease were chosen for the cell
      proliferation assay. RESULTS: Twenty new compounds (1a-t) with E configuration
      have been designed, synthesized and bioassayed. Their structural features were
      determined by nuclear magnetic resonance (NMR) spectra, low- and high-resolution
      mass spectra, and confirmed by X-ray crystallography. Although the enzyme assay
      showed a weak inhibition effect against the epidermal growth factor receptor,
      vascular endothelial growth factor receptor, fibroblast growth factor receptor
      and platelet-derived growth factor receptor tyrosine kinases, the cell-based
      antitumor activity was promising. Compounds 1 g and 1 h showed higher inhibitory
      activity toward the A-549 and MDA-MB-468 cell lines with IC(50 ) of 0.065-9.4
      micromol/L. CONCLUSION: This study provides a new template for further
      development of potent antitumor drugs.

PMID- 17184595
TI  - Simvastatin could prevent increase of the serum MMP-9/TIMP-1 ratio in acute
      ischaemic stroke.
AB  - MMP-9 plays an important role in the pathogenesis of AIS and predicts
      haemorrhagic transformation of the ischaemic focus. The aim of our study was to
      analyse both serum MMP-9 and its most specific endogenous inhibitor (TIMP-1)
      levels in AIS and to check whether HMG-CoA reductase inhibitor (simvastatin)
      affects the MMP-9/TIMP-1 ratio value. Fifty patients with AIS were randomly
      divided into two groups: Group I (N = 25) treated with 40 mg/day with simvastatin
      within 24 hours after the onset of stroke and Group II (N = 25) non-treated with
      statin. To evaluate MMP-9 and TIMP-1 serum levels, the ELISA method was used. The
      serum MMP-9 level was significantly elevated on the 7th day of stroke in both
      groups (from 668 to 862 ng/ml and 670 to 855 ng/ml, respectively, in Group I and
      II). The serum TIMP-1 level was also elevated on the 7th day of stroke in both
      groups but the results were not significant. The MMP-9/TIMP-1 ratio was elevated
      on the 7th day of stroke in both groups, but the result was significant only in
      the Group II (P < 0.01). These findings indicate that simvastatin given during 24
      hours after the onset of stroke could have an influence on the MMP-9/TIMP-1 ratio
      during AIS.

PMID- 17184596
TI  - Polymorphisms of the MDR1 gene in the Czech population.
AB  - There exists a marked inter-individual variability of P-glycoprotein expression
      and activity, which can be of clinical importance due to the large number of
      drugs that are substrates for the transporter. Previously identified
      polymorphisms in the MDR1 gene belong to important factors causing this
      phenomenon. Our aim was to investigate the frequency of major functional SNPs of
      the MDR1 gene coding for P-glycoprotein in the Czech population. DNA was isolated
      from whole blood of 189 healthy, young and unrelated subjects (99 females and 90
      males, aged from 23 to 28 years). The genotypes of polymorphic positions C3435T,
      G2677T/A, C1236T and T-76A were determined by PCR-RFLP. Observed allelic
      frequencies were 56.5%, 46.0%, 0.53%, 44.5% and 37.6% for the alleles 3435T,
      2677T, 2677A, 1236T and -76A, respectively. We have found 64 subjects homozygous
      for 3435T, 42 for 2677T, 40 for 1236T and 31 for -76A alleles. The allelic
      distribution complies well with Hardy-Weinberg equilibrium. Allelic frequencies
      of functionally important MDR1 variants are in the Czech population similar to
      that of other Caucasian populations.

PMID- 17184597
TI  - Preliminary report of expression of bax in oral cavity pathologies.
AB  - Bax is considered one of major effectors of apoptosis--programmed cell death.
      Immunohistochemical analysis of in vitro patterns of bax expression was mostly
      investigated in mammalian cell lines and tissues. The present study is the first
      in vivo molecular analysis of bax expression in oral cavity pathologies. The
      study population consisted of 45 patients with hyperplasia, neoplasm in situ
      malignancy, and carcinoma. Biopsies were taken from incision line, tumour
      section, and healthy tissue. bax expression was investigated depending on the
      site of biopsy material sampling and final histopathology result. No
      statistically significant difference was demonstrated in bax expression between
      four hyperplasia subgroups. However, statistically significant differences in bax
      expression were found between the three basic study groups (P = 0.001).
      Statistically significant differences in bax expression were demonstrated
      depending on tissue collection site (P = 0.0002). We conclude that differences in
      bax expression may play a role in the pathogenesis of neoplastic disease.

PMID- 17184598
TI  - Polymorphisms of dopamine-beta-hydroxylase in ADHD children.
AB  - ADHD is a multifactorial disorder clinically characterized by inattentiveness,
      impulsivity and hyperactivity. The occurrence of this disorder varies between 3
      and 6% of the child population, with boys predominating over girls at a ratio of
      3 : 1 or more. Dysfunction or imbalance between the dopaminergic and
      noradrenergic systems of neurotransmitters can play a key role in the ADHD
      pathophysiology. Alteration of the dopamine/noradrenaline levels can result in
      hyperactivity. DBH is an enzyme responsible for the conversion of dopamine into
      noradrenaline. The DBH protein is released in response to stimulation. DBH
      activity, derived largely from sympathetic nerves, can be measured in human
      plasma. Patients with ADHD showed decreased activities of DBH in serum and urine.
      Low DBH levels correlate indirectly with the seriousness of the hyperkinetic
      syndrome in children (Galvin et al., 1995, 1997). In the DBH gene, the G444A,
      G910T, C1603T, C1912T, C-1021T, 5'-ins/del and TaqI polymorphisms occur
      frequently and may affect the function of gene products or modify gene expression
      and thus influence the progression of ADHD. This article reviews the DBH itself
      and polymorphisms in the DBH gene that influence the DBH activity in the serum
      and the CSF level of DBH. All those are evaluated in connection with ADHD.

PMID- 17184599
TI  - Depletion of Treg cells augments the therapeutic effect of cancer vaccines.

PMID- 17184600
TI  - [The human papillomavirus vaccine and the incorporation of pediatrics in cervical
      cancer prevention].

PMID- 17184601
TI  - [Study of the introduction of the European Credit Transfer System (ECTS) in
      pediatrics and modification of the teaching methodology].
AB  - INTRODUCTION: Spanish medical faculties have initiated the new curriculum reform
      process within the framework of the European Higher Education Area and are
      required to incorporate the European Credit Transfer System (ECTS) to new syllabi
      before 2010. OBJECTIVES: To test the introduction of the ECTS in pediatrics and
      modify the teaching methodology. STUDY DESIGN: The theoretical and practical
      programs were adapted; academic objectives and a student evaluation system were
      established. Students were surveyed on starting the second term of the 2004-05
      academic year before the theory examination and again on terminating the academic
      year: a 5-point Likert-type scale was used for responses. Priorities for generic
      and specific competencies selected by students were compared with those selected
      by the National Deans Conference (NDC). The results were analyzed using non
      parametric tests. RESULTS: Fifteen credits became 11 ECTS, with 297 student
      working hours. The theory program was reduced from 80 to 52 lessons. The students
      prepared 14 tutor-supervised case presentations. The teaching staff considered
      that learning of theory was similar to previous years (66 %) and that practical
      learning improved (73.3 %). The students thought the program should continue
      (73.2 %) but 98.8 % considered the workload excessive. The students believed that
      their practical training and their ability to prepare and make case presentations
      significantly improved during the semester. Academic performance was
      significantly higher than that in students of the previous year. Students agreed
      with NDC priorities for 9/9 general and 4/17 specific competencies. Estimation of
      workload by students was significantly higher than that by staff, and 73.3 % of
      the students believed that workload should be reduced and the examination system
      improved. CONCLUSIONS: Introducing the ECTS improved academic performance,
      practical training, and self-directed learning. The project was satisfactory for
      staff and students. Student workload was underestimated.

PMID- 17184602
TI  - [Triptorelin therapy in girls with central precocious puberty increases body mass
      index].
AB  - INTRODUCTION: The most important complications of central precocious puberty
      (CPP) in girls are loss of height and multiple psychosocial problems. OBJECTIVES:
      To study the effect of triptorelin therapy in a cohort of girls with CPP.
      PATIENTS AND METHODS: Thirty-four girls diagnosed with organic or idiopathic CPP
      and treated with monthly triptorelin were studied. Age, height in standard
      deviation (SD), bone age (Greulich and Pyle), height prediction (Bayle-Pinneau),
      body mass index (BMI) in SD, uterine size (pelvic ultrasound), target height,
      cranial magnetic resonance imaging, triptorelin dose, and treatment duration were
      studied. RESULTS: Triptorelin produced a statistically significant reduction in
      growth velocity and an increase in BMI after 1 year of therapy and these changes
      were maintained after discontinuation of therapy. Adult height in these patients
      was in accordance with their target genetic height, as well as with their
      predicted height according to the method of Bayley-Pinneau. No significant
      differences were found between age of menarche in our patients and in controls.
      Adult height in patients with organic CPP was significantly lower than that in
      patients with idiopathic CPP. CONCLUSIONS: 1. Triptorelin can increase BMI in
      girls with CPP. 2. The presence of an organic cause in patients with CPP worsens
      the prognosis for adult height. 3. The Bayley-Pinneau prediction method for
      "average" bone age is useful for establishing a prognosis of adult height in
      girls with CPP treated with triptorelin.

PMID- 17184603
TI  - [Central precocious puberty is associated with a high prevalence of organic
      disease].
AB  - INTRODUCTION: The incidence of central precocious puberty (CPP) is lower in boys
      than in girls; however, the presence of organic disease is more common in boys.
      OBJECTIVES: To investigate the percentage of CPP secondary to organic disease in
      boys and to analyze their clinical and biological characteristics at diagnosis,
      during follow-up, and at the end of therapy. PATIENTS AND METHODS: Eight boys
      with a diagnosis of CPP treated with triptorelin every 28 days were included.
      Age, height in standard deviation (SD), body mass index (BMI) in SD, growth
      velocity in SD, bone age (Greulich and Pyle), predicted height (Bayle-Pinneau),
      and target height were analyzed. Testicular volume was measured (according to
      Prader standards) and peak lutein hormone (LH) values and testosterone levels
      were determined after gonadotropin-releasing hormone (GnRH) stimulus. RESULTS:
      Seventy-five percent of the patients with CPP had organic disease. After
      treatment with triptorelin, growth reduction significantly decreased. In
      contrast, no changes were seen in the difference between bone age and
      chronological age, due to the slight difference found at diagnosis. Likewise,
      during treatment, there was no LH peak and testosterone levels were lower than
      0.5 ng/ml in response to GnRH stimulus. No changes were observed in weight or
      BMI. Three patients reached an adult height similar to their genetic height and
      their predicted height, as estimated by the Bayle-Pinneau method. CONCLUSIONS: 1.
      Among boys with CPP we found a substantial number of patients with organic
      disease. 2. Adult height after treatment with triptorelin can reach the normal
      range. 3. Determination of testosterone levels can be useful in the follow-up of
      these children during treatment.

PMID- 17184604
TI  - [Cardiorespiratory arrest in children with trauma].
AB  - OBJECTIVE: To analyze the characteristics and outcome of cardiorespiratory arrest
      secondary to trauma in children. PATIENTS AND METHODS: We performed a secondary
      analysis of data from a prospective, multicenter study of cardiorespiratory
      arrest in children. Data were recorded according to the Utstein style. Twenty
      eight children (age range: 7 days to 16 years) with cardiorespiratory arrest
      secondary to trauma were evaluated. The outcome variables were return of
      spontaneous circulation, sustained (more than 20 minutes) return of spontaneous
      circulation (initial survival), and survival at hospital discharge (final
      survival) in relation to the characteristics of the cardiorespiratory arrest and
      cardiopulmonary resuscitation. Neurological and general performance outcome was
      assessed by means of the Pediatric Cerebral Performance Category scale and the
      Pediatric Overall Performance Category scale. RESULTS: Return of spontaneous
      circulation was obtained in 18 patients (64.2 %), initial survival was achieved
      in 14 (50 %) and final survival was achieved in three (10.7 %) (two without
      neurological sequelae and one with vegetative status). Final survival was
      significantly higher in patients with respiratory arrest (33.3 %) than in those
      with cardiac arrest (4.5 %), p = 0.04. Final survival was also higher in patients
      with a duration of cardiopulmonary resuscitation shorter than 20 minutes (27.2 %)
      than in the remaining patients (0 %), p =0.05. The two survivors without
      neurologic sequelae had respiratory arrest. CONCLUSIONS: Survival until hospital
      discharge in children with cardiorespiratory arrest secondary to trauma is lower
      than that in children with cardiorespiratory arrest. Patients with respiratory
      arrest when resuscitation is started and those with a duration of cardiopulmonary
      resuscitation of less than 20 minutes showed better survival than the remaining
      patients.

PMID- 17184605
TI  - [Intake of fermented milk containing Lactobacillus casei DN-114 001 and its
      effect on gut flora].
AB  - OBJECTIVE: To study the gut flora in infants who received fermented milk
      containing Lactobacillus casei and Streptococcus termophilus and its effect on
      secretory immunoglobulin levels. MATERIAL AND METHODS: An experimental,
      randomized, prospective, parallel group study was carried out. Thirty-five
      infants were included (18 in the treatment group and 17 in the control group)
      with a mean age of 2 years (SD: 0.6 years; range: 1-3 years). The experimental
      group received both fermented milk (0.5 l/day) containing L. casei and S.
      termophilus for 6 weeks and standard cow's milk for the following 6 weeks. The
      control group received standard cow's milk (0.5 l/day) for 12 weeks. Secretory
      IgA levels in saliva were evaluated in the experimental group at the start of the
      study (baseline levels) and 6 weeks later. In both groups, stools were collected
      to study gut flora at 0, 6 and 12 week. RESULTS: Secretory IgA levels
      significantly increased (p =0.0063) from a mean baseline value of 2.5 mg/dl to a
      mean of 3.4 mg/dl at 6 weeks. Gram-negative aerobic flora were decreased in the
      experimental group after 6 weeks compared with the control group (p =0.0203). The
      number of infants with Lactobacillus spp in their gut flora was greater in the
      experimental group than in the control group at week 6 and this difference was
      statistically significant (p =0.028) at week 12. Conclusion The present study
      provides evidence of L. casei survival in the gastrointestinal tract and of its
      effect of increasing secretory IgA.

PMID- 17184606
TI  - [Anthropometric patterns in non-Caucasian full-term neonates of African, Moroccan
      and South American origin born in Catalonia (Spain)].
AB  - INTRODUCTION: The rise in immigration to Spain in recent decades has increased
      the number of non-Caucasian newborns in our environment. The aims of this study
      were to establish normal intrauterine development values for weight, length and
      head circumference in a population of non-Caucasian full-term newborns (FTN).
      PATIENTS AND METHODS: We studied 2,444 healthy full-term singleton newborns (37
      42 weeks' gestational age; 1,230 boys, 1,214 girls) with the following ethnic
      origins: black (n =1,257; 622 boys, 635 girls), Moroccan (n =520; 297 boys, 223
      girls) and South-American (n =667; 356 boys, 311 girls). Mean values and standard
      deviations were estimated for each week of gestation for sex and race and these
      values were compared with those of a Spanish population of the same gestational
      age and sex. RESULTS: Anthropometric values in black FTN were similar to those of
      the Catalan population. By contrast, these values were higher in Moroccans and
      South-American FTN than in the native population. Statistically-significant
      differences were observed in all the parameters evaluated from the 38th week of
      gestation in full-term Moroccan newborns compared with the reference population.
      Statistically significant differences were observed in full-term South-American
      newborns from the 38th week of gestation in girls and from the 40th week in boys.
      The presence of sexual dimorphism in the anthropometric patterns evaluated was
      not constant at all the gestational ages evaluated. CONCLUSIONS: Anthropometric
      patterns of the Spanish Caucasian FTN population are not extrapolable to FTN of
      other ethnicities.

PMID- 17184608
TI  - [Bases for adequate complementary feeding in infants and young children].
AB  - Infants can be exclusively breast fed or formula fed for the first 6 months of
      life and their nutritional requirements are completely fulfilled. However, from 6
      months onwards, human milk is not sufficient to supply all the nutrients
      necessary for infants and young children. Therefore, adequate supplementary
      feeding, in terms of both quantity and quality, should be provided. The present
      article aims to describe the scientific bases for practical recommendations on
      complementary feeding during infancy and early childhood, which may be useful to
      pediatricians and should serve to improve the health status of the infant
      population in Spain. In this sense, the new international recommendations for
      energy, protein and other nutrient requirements are reviewed. In Spain, the law
      applicable to manufacturing infant cereals and homogenized infant foods is that
      published by the European Union in specific directives. However, taking into
      consideration new advances in knowledge of nutritional requirements, we have
      considered a number of issues that could be relevant for the manufacture of these
      foods. Finally, we propose a series of basic principles that should serve as a
      guide for the complementary feeding of infants (whether breast fed, formula fed,
      or receiving mixed feeding) and young children. These recommendations are
      particularly addressed to pediatricians working in primary health services.

PMID- 17184607
TI  - [Human papillomavirus vaccines: a new challenge for pediatricians].
AB  - Human papillomavirus (HPV) infections are the most common sexually transmitted
      infections in the world. This infection is a necessary cause of cervical cancer,
      has been related to other forms of anogenital, airway and digestive cancers, and
      also causes anogenital warts. The recent advances in HPV prophylactic vaccines
      and their imminent commercial availability will post a new challenge to
      pediatricians: the indication and administration of these vaccines for the
      prevention of HPV infection, and consequently, of cervical cancer and other HPV
      related diseases. The present article reviews the essentials of HPV infection,
      its relationship with cervical cancer, the advances in prophylactic HPV vaccines,
      and the role of the pediatrician in this context.

PMID- 17184609
TI  - [Episodic hypertension in postural orthostatic tachycardia syndrome].
AB  - We report the case of a 17-year-old woman who presented to the emergency
      department on several occasions due to palpitations, tachycardia, syncope, short
      spells of dizziness and light-headedness with complete spontaneous recovery, and
      hypertension. The patient had been evaluated by several specialists, and multiple
      complementary examinations had revealed no abnormalities that could explain the
      symptoms. Due to suspicion of orthostatic intolerance or postural orthostatic
      tachycardia syndrome with hypertension, the patient underwent a 60-degree tilt
      table test, which confirmed the diagnosis. The patient was successfully treated
      with bisoprolol. The physiopathological mechanisms, diagnosis, and treatment of
      this syndrome are reviewed.

PMID- 17184610
TI  - [Unilateral exophthalmos and systemic lupus erythematosus].

PMID- 17184611
TI  - [Duane syndrome type I].

PMID- 17184612
TI  - [Multiple exostoses].

PMID- 17184613
TI  - [Torticolis and vertigo paroxistico].

PMID- 17184614
TI  - [Postoperative meralgia paresthetica].

PMID- 17184615
TI  - [Ataxia as an adverse reaction to yellow fever vaccine].

PMID- 17184616
TI  - [Cat scratch disease].

PMID- 17184617
TI  - [Safety of MMR immunization in egg-allergic children].

PMID- 17184618
TI  - [Sigmoid sinus thrombosis following otitis media].

PMID- 17184619
TI  - [Cervicoscapular mass].

PMID- 17184620
TI  - Primary sarcoma of the thoracic aorta.

PMID- 17184621
TI  - Bilateral congenital cystic adenomatoid malformation.

PMID- 17184622
TI  - At last, inequities in reimbursement modified by real evidence-based data.

PMID- 17184623
TI  - Physician payment for 2007: a description of the process by which major changes
      in valuation of cardiothoracic surgical procedures occurred.
AB  - Throughout the last 3 years, the Society of Thoracic Surgeons (STS) has put forth
      a major effort towards more accurate valuation of the work performed by
      cardiothoracic surgeons. The culmination of these efforts was realized on
      November 1, 2006, when the Centers for Medicare & Medicaid Services published the
      Final Rule which markedly increased the physician work values for the most
      frequently performed cardiothoracic surgery procedures. This article recounts the
      innovative approach taken by the STS during these extended efforts.

PMID- 17184624
TI  - When is HIT really HIT?

PMID- 17184625
TI  - Self-management of oral anticoagulation therapy improves long-term survival in
      patients with mechanical heart valve replacement.
AB  - BACKGROUND: The Early Self-Controlled Anticoagulation Trial has demonstrated that
      in patients with mechanical heart valve replacement self-management of oral
      anticoagulation results in less major thromboembolic events than conventional
      measurement by the general practitioner. However, the effects of self-management
      on long-term survival are currently not known. METHODS: Nine hundred thirty
      patients participated in a follow-up study of the aforementioned trial (488 from
      the self-management group and 442 from the conventional group). Long-term
      survival was assessed 12 years after the study began using the intent-to treat
      analysis as well as the per protocol analysis. Univariate and multivariate
      analyses were performed in order to assess independent predictors of survival.
      RESULTS: In total, the 930 patients accrued 8,315 patient-years of observation.
      During follow-up, 236 patients died. According to the intent-to treat analysis,
      10-year survival was 76.1% in the conventional group and 84.5% in the self
      management group. The corresponding values for the per protocol analysis were
      67.7% and 80.6%, respectively. Age, kind of valve surgery, and study group were
      independent predictors of survival. Self-management of oral anticoagulation
      increased long-term survival by 23% (intent-to-treat analysis) and 33% (per
      protocol analysis), respectively, compared with conventional measurement by the
      general practitioner. Possible reasons for these advantageous results in the self
      management group are fewer thromboembolic events due to a higher percentage of
      international normalized ratio values lying in the target range compared with the
      conventional group. CONCLUSIONS: Data indicate that self-management of oral
      anticoagulation is a promising strategy in order to increase long-term survival
      in patients with mechanical prosthetic valves.

PMID- 17184626
TI  - Long-term outcomes in valve replacement surgery for infective endocarditis.
AB  - BACKGROUND: Infective endocarditis is associated with a high rate of long-term
      mortality. Patients with a history of intravenous drug use (IVDU) are at
      increased risk for infective endocarditis. However, few studies have reported
      results of surgical treatment on this population. We present 19.5 years of
      experience with surgically treated patients with infective endocarditis. METHODS:
      A retrospective study of all cardiac surgeries with a diagnosis of infective
      endocarditis at a single institution from 1986 to 2005 was performed. Logistic
      stepwise regression with an end point of operative mortality was done. Variables
      were age, gender, race, history of drug use, previous valve surgery, and previous
      valve replacement. Perioperative and outcome variables were compared between IVDU
      and non-IVDU populations. RESULTS: The IVDU population required surgery at a
      younger age (39 +/- 9 years versus 54 +/- 15 years; p < 0.001). Overall operative
      mortality was 12% (41/346). The perioperative complication rate was similar for
      both groups. When adjusted for age, the two groups had similar long-term survival
      (p = 0.78). Kaplan-Meier estimator showed that survival at 10 and 15 years was
      66% and 54% for IVDU and 56% and 42% for non-IVDU (number at risk, 19, 11, and
      61, 28, respectively; p = 0.137). Reoperation for recurrent infective
      endocarditis was necessary in 9 (17%) of 52 of the IVDU group versus 14 (5%) of
      270 of the non-IVDU group (p = 0.03). CONCLUSIONS: Patients with a history of
      IVDU required reoperation for recurrent infective endocarditis at a significantly
      higher rate than the non-IVDU patients. Long-term survival was similar between
      the younger IVDU population and the older non-IVDU population. Anticipated life
      span is one of many factors when considering prosthetic valve choice in this
      population.

PMID- 17184627
TI  - Subcoronary Ross procedure in patients with active endocarditis.
AB  - BACKGROUND: The Ross procedure has gained increasing interest as an attractive
      alternative to a prosthetic aortic valve substitute within the last decade.
      Because of a probably better resistance to infection as one of its advantages,
      the pulmonary autograft is theoretically preferable for active endocarditis.
      METHODS: Between June 1994 and July 2003, the Ross procedure was performed using
      the subcoronary and inclusion technique in 296 patients (231 male, 65 female).
      Twenty patients had an active endocarditis of the aortic valve at the time of
      operation. A bicuspid valve was present in 10 patients. One patient had previous
      aortic valve surgery. Clinical and echocardiographic follow-up was complete.
      RESULTS: Early mortality was 1, late mortality was 0. There were no recurrence of
      endocarditis and no neurologic events during the mean follow-up of 47.3 +/- 28.6
      months. All patients were in New York Heart Association class I. Mean and maximum
      pressure gradient across the autograft was 3.5 +/- 2.0 and 6.5 +/- 3.4,
      respectively, with no autograft insufficiency in 15, 1+ in 4. Comparing
      postoperative with the last investigations, there were no significant changes of
      pressure gradients or grade of regurgitation. Mean and maximum homograft pressure
      gradients were 7.9 +/- 3.7 and 16.2 +/- 8.1 mm Hg, respectively, at last
      investigation; most patients had no or mild homograft regurgitation (0+, n = 13;
      1+, n = 5; 2+, n = 1). CONCLUSIONS: Native valve endocarditis can be treated with
      excellent results using the Ross procedure with the subcoronary and inclusion
      technique, with low mortality and morbidity rates and a very low recurrence rate
      of endocarditis.

PMID- 17184628
TI  - Multicentered European study on safety and effectiveness of the On-X prosthetic
      heart valve: intermediate follow-up.
AB  - BACKGROUND: This study was performed to determine the safety and effectiveness of
      the On-X valve, a novel mechanical valve substitute. METHODS: Eleven centers
      participated in a European, multicentered, longitudinal, nonrandomized study of
      the On-X valve performance. Isolated aortic or mitral valve replacement with an
      On-X valve was studied in 301 patients. Aortic valve replacement was performed in
      184 patients (average follow-up, 5.0 years), whereas mitral valve replacement was
      performed in 117 patients (average follow-up, 4.4 years). RESULTS: In patients
      with aortic valve replacement, mean transvalvular pressure gradients ranged from
      8.3 to 4.7 mm Hg and effective orifice areas from 1.5 to 2.7 cm2, for 19-mm
      through 25-mm valves, respectively. After mitral valve replacement, mean gradient
      was 4.2 mm Hg and effective orifice area by pressure half-time was 2.6 cm2
      regardless of valve size. Hemolysis was low, with postoperative serum lactate
      dehydrogenase at 225 +/- 41 IU (mean +/- standard deviation) or 253 +/- 65 IU,
      after aortic valve replacement or mitral valve replacement, respectively (upper
      normal value, 250 IU). At 1 year or greater postoperatively, 91.6% of patients
      after aortic valve replacement and 84.6% after mitral valve replacement were in
      New York Heart Association functional class I or II. Adverse event rates in
      percent per patient-year after aortic valve replacement or mitral valve
      replacement were thromboembolism, 0.88 or 1.76; thrombosis, 0.11 or 0.20;
      bleeding, 0.77 or 1.96, respectively. Late mortality was 1.97% or 2.55%,
      respectively. CONCLUSIONS: At the intermediate follow-up, the On-X valve
      exhibited improved hemodynamics, low hemolysis with in-range lactate
      dehydrogenase, and low adverse event rates, particularly in the aortic position.

PMID- 17184629
TI  - Altered myocardial shear strains are associated with chronic ischemic mitral
      regurgitation.
AB  - BACKGROUND: Ischemic mitral regurgitation (IMR) limits life expectancy and can
      lead to postinfarction global left ventricular (LV) dilatation and remodeling,
      the pathogenesis of which is not completely known. We tested the hypothesis that
      IMR perturbs adjacent myocardial LV systolic strains. METHODS: Thirteen sheep had
      three columns of miniature beads inserted across the lateral LV wall, with
      additional epicardial markers silhouetting the ventricle. One week later
      posterolateral infarction was created. Seven weeks thereafter, the animals were
      divided into two groups according to severity of IMR (< or = 1+, n = 7, IMR[-] vs
      > or = 2+, n = 6, IMR[+]). Four dimensional marker coordinates and quantitative
      histology were used to calculate ventricular volumes, transmural myocardial
      systolic strains, and systolic fiber shortening. RESULTS: Seven weeks after
      infarction, end-diastolic (ED) volume increased similarly in both groups, end
      systolic (ES) E13 (circumferential-radial) shear increased in both groups, but
      more so in IMR(+) than IMR(-) (+0.12 vs 0.04, p < 0.005), and E12
      (circumferential-longitudinal) shear increased in IMR(-) but not IMR(+) (+0.04 vs
      -0.01, p < 0.005). There were no significant differences in ED or ES remodeling
      strains or systolic fiber shortening between IMR(-) and IMR(+). CONCLUSIONS: An
      equivalent increase in LV end-diastolic (ED) volume in both groups, coupled with
      unchanged ED and end-systolic remodeling strains as well as systolic
      circumferential, longitudinal, and radial strains, argue against a global LV or
      regional myocardial geometric basis for the cardiomyopathy associated with IMR.
      Further, similar systolic fiber shortening in both groups militates against an
      intracellular (cardiomyocyte) mechanism. The differences in subepicardial E12 and
      E13 shears, however, suggest a causal role of altered interfiber (cytoskeleton
      and extracellular-matrix) interactions.

PMID- 17184630
TI  - Simple risk models to predict surgical mortality in acute type A aortic
      dissection: the International Registry of Acute Aortic Dissection score.
AB  - BACKGROUND: Surgical mortality for acute type A aortic dissection is frequently
      related to preoperative clinical conditions. We report a predictive score to
      identify risk of death that may be helpful to assist surgeons who are considering
      whether to proceed with surgical correction in the case of patients in extreme
      clinical risk. METHODS: Surgical outcome of 682 patients enrolled in the
      International Registry of Acute Aortic Dissection from 1996 to 2003 was analyzed.
      Two different models were used. The initial model included only preoperative
      variables such as demographics, history, symptoms, signs, and diagnostic methods
      (model 1). The second model also tested intraoperative hemodynamic and surgical
      variables (model 2). A bedside risk prediction tool to predict operative
      mortality in individual patients was developed. RESULTS: The overall in-hospital
      surgical mortality was 23.9%. Independent preoperative predictors of mortality in
      model 1 were age greater than 70 years, prior cardiac surgery, hypotension
      (systolic blood pressure less than 100 mm Hg) or shock at presentation, migrating
      pain, cardiac tamponade, any pulse deficit, and electrocardiogram with findings
      of myocardial ischemia or infarction. In model 2, other predictors of surgical
      death were intraoperative hypotension, a right ventricle dysfunction at surgery,
      and a necessity to perform coronary revascularization. An independent predictor
      for favorable surgical outcome was right hemiarch replacement. CONCLUSIONS:
      Surgery in unstable patients with acute type A aortic dissection can be highly
      unsuccessful. The International Registry of Acute Aortic Dissection risk models
      predict in-hospital mortality using a multivariable risk prediction tool, useful
      for surgeons and patients as they consider their surgical risk and the pros and
      cons of embarking on high-risk surgery.

PMID- 17184631
TI  - Multivariate predictors of heart transplantation outcomes in the era of chronic
      mechanical circulatory support.
AB  - BACKGROUND: Determining which pretransplantation (TX) characteristics predict the
      development of chronic renal dysfunction (CRD) or death after heart TX would
      enable more accurate risk assessment at the time of candidate evaluation.
      METHODS: A cohort of 278 patients underwent TX in three hospitals between 1993
      and 2002. Predictive models for CRD (serum creatinine consistently above 2 mg/dL)
      and allograft loss (death or re-TX) were constructed using logistic and Cox
      regression, respectively. RESULTS: Using logistic regression, CRD was more likely
      to develop in TX patients if they had a larger body surface area (odds ratio [OR]
      = 5.8 per m2, 95% confidence interval [CI] = 1.04 to 31.9, p = 0.04) or were
      inotrope dependent (OR = 1.8, 95% CI = 0.90 to 3.7, p = 0.09). Notably, the
      implementation of mechanical circulatory support as bridge to transplantation
      decreased the risk of CRD (OR = 0.30, 95% CI = 0.12 to 0.72, p = 0.007). Cox
      analysis demonstrated independent predictive ability of improved survival for
      males (hazard ratio [HR] = 0.42, 95% CI = 0.21 to 0.83, p = 0.01). Worse survival
      was observed with prior sternotomy (HR = 3.5, 95% CI = 2.0 to 6.0, p < 0.001),
      diabetes mellitus (HR = 1.9, 95% CI = 0.98 to 3.9, p = 0.06), and elevated serum
      creatinine (HR = 2.8 per mg/dL, 95% CI = 1.3 to 5.8, p = 0.007). CONCLUSIONS:
      Certain pretransplant characteristics clearly predispose a patient to the
      development of CRD or increased mortality after heart transplantation.
      Interestingly, the risk of CRD after heart transplantation is greater for
      patients bridged to transplant with inotropes than with mechanical circulatory
      support. When hemodynamically indicated, timely implementation of pretransplant
      mechanical circulatory support should be considered.

PMID- 17184632
TI  - Effect of sildenafil on pulmonary artery pressure, systemic pressure, and nitric
      oxide utilization in patients with left ventricular assist devices.
AB  - BACKGROUND: Pulmonary artery hypertension can complicate the early postoperative
      care of patients with left ventricular assist devices (LVADs). Inhaled nitric
      oxide (INO) is frequently used to manipulate pulmonary resistance after LVADs
      have been placed. We evaluated the effect of oral sildenafil therapy on pulmonary
      artery pressure, systemic pressure, and nitric oxide utilization. METHODS: After
      Institutional Review Board approval, the records of 10 consecutive adult patients
      with LVADs and pulmonary hypertension who received sildenafil were reviewed.
      Demographics, surgical history, INO use, inotrope requirements, and hemodynamic
      response to oral sildenafil at multiple intervals were collected. Hemodynamic
      data were analyzed with a two-way analysis of variance of repeated measures with
      correction for multiple comparisons. RESULTS: There were 8 men and 2 women with 6
      Heartmate XVE LVADs and 4 Thoratec LVADs (both, Thoratec, Pleasanton,
      California). When weaning was attempted, 8 patients who received INO demonstrated
      rebound pulmonary hypertension or increased right heart dysfunction. All patients
      were on inotropic therapy with dobutamine and milrinone. Sildenafil produced a
      significant reduction in pulmonary artery systolic pressure within 90 minutes of
      oral administration (p = 0.042). Significant changes in systolic blood pressure,
      mean arterial pressure, systemic vascular resistance, and heart rate were not
      observed. All 8 patients receiving INO were weaned within 12 hours without
      recurrent pulmonary hypertension. All 10 patients were weaned from inotropic
      support within 72 hours. No patient suffered right-side heart failure requiring
      intervention. CONCLUSIONS: Oral sildenafil represents a useful adjunctive therapy
      for patients with LVADs. In our series, it provided additional reduction of
      pulmonary artery pressure, and facilitated weaning from INO and inotropes without
      deleterious hemodynamic consequences.

PMID- 17184633
TI  - Impact of heparin-induced thrombocytopenia on outcome in patients with
      ventricular assist device support: single-institution experience in 358
      consecutive patients.
AB  - BACKGROUND: Cardiac surgical patients are at an approximate 1% to 2% risk of
      experiencing heparin-induced thrombocytopenia (HIT), a severe immune-mediated
      disease that is associated with thromboembolic events. We assessed the occurrence
      of this disease and its influence on clinical outcome in patients after
      implantation of a ventricular assist device (VAD). METHODS: This retrospective
      analysis assessed data from our adult patient VAD program between the years 2000
      and 2005. Patients were divided into three groups: those without confirmed HIT
      ((non)HIT), those in whom the diagnosis of HIT was made before VAD implantation
      (HIT(pre)), and those who experienced HIT after VAD implantation (HIT(post)). End
      points assessed were procedural success, as defined by discharge from hospital or
      transplantation or recovery of the failing heart, as opposed to death before
      procedural success was achieved. RESULTS: The data of 358 consecutive patients
      were analyzed. There were 330 (non)HIT patients (91.6%), 15 HIT(pre) patients
      (4.5%), and 13 HIT(post) patients (3.9%). Procedural success was observed in 50%
      of (non)HIT patients, 67% of HIT(pre) patients, and 31% of HIT(post) patients.
      CONCLUSIONS: Heparin-induced thrombocytopenia is a frequent complication in VAD
      patients and is associated with detrimental outcome when occurring after
      implantation. Preoperative diagnosis of HIT and the implementation of alternative
      anticoagulation procedures appears to be associated with better results. Early
      detection of HIT antibodies before or shortly after VAD implantation and
      immediate implementation of an alternative anticoagulation regimen may be a
      strategy to improve outcome.

PMID- 17184634
TI  - Superior transseptal approach to mitral valve is associated with a higher need
      for pacemaker implantation than the left atrial approach.
AB  - BACKGROUND: Several studies suggest that the superior transseptal approach to
      mitral valve surgery leads to sinus node dysfunction. The clinical consequences
      are not known. METHODS: Consecutive patients undergoing surgery for mitral valve
      disease from November 16, 1994 through January 26, 2004 were retrospectively
      evaluated. The surgeons used either the superior transseptal (group A) or left
      atrial approach (group B). The risk of pacemaker implantation associated with the
      superior transseptal approach as compared with the left atrial approach was
      estimated using the multivariate Cox regression analysis to adjust for possible
      confounders. RESULTS: We included 577 patients, 150 in group A and 427 in group
      B. Forty-four patients had a pacemaker implanted after the surgery; 17 in group A
      and 27 in group B (p = 0.010). The superior transseptal approach was an
      independent risk factor of pacemaker implantation in multivariate analysis
      (hazard ratio 2.2 [1.2 to 4.1], p = 0.014). Nineteen patients had a pacemaker
      implanted because of sinus node dysfunction; 9 in group A and 10 in group B (p =
      0.017). Group A was an independent predictor of pacemaker implantation because of
      sinus node dysfunction in bivariate analyses. The risk of pacemaker implantation
      because of atrioventricular conduction disturbances was not different between the
      groups (p = 0.178). CONCLUSIONS: The superior transseptal approach has a higher
      risk of clinically significant sinus node dysfunction than the left atrial
      approach.

PMID- 17184635
TI  - Clinical utility of tissue Doppler imaging in prediction of atrial fibrillation
      after coronary artery bypass grafting.
AB  - BACKGROUND: Atrial systolic dysfunction in patients with coronary artery disease
      might influence the development of atrial fibrillation after coronary artery
      bypass grafting (CABG). Tissue Doppler imaging of the mitral annulus during
      atrial systole has proved to quantify, accurately, left atrial contractile
      function. Therefore, the aim of the present study was to investigate the
      correlation between preoperative left atrial dysfunction assessed by tissue
      Doppler and postoperative atrial fibrillation after CABG. METHODS: We studied a
      total of 96 patients (mean age 67 +/- 6 years; range, 55 to 81) undergoing CABG
      who were preoperatively in sinus rhythm. All patients underwent a preoperative
      transthoracic echocardiography with tissue Doppler evaluation. Until the day of
      discharge, all patients were monitored with continuous electrocardiographic
      telemetry. RESULTS: There were no hospital deaths. Postoperative atrial
      fibrillation was recorded in 24 of 96 patients (25%). Patients with postoperative
      atrial fibrillation were significantly older (70 +/- 6 vs 65 +/- 8 years; p =
      0.006), had a preoperative larger left atrium diameter (38 +/- 5 vs 36 +/- 4 mm;
      p = 0.045), a larger left atrium area (13.2 +/- 3.4 vs 11.5 +/- 2.3 cm2; p =
      0.007), and a lower peak atrial systolic mitral annular tissue Doppler velocity
      (10 +/- 3 vs 13 +/- 5 cm/second; p = 0.01). Stepwise logistic regression analysis
      showed that age 70 years or greater (p = 0.02; odds ratio [OR] 2.0), preoperative
      medication with beta-blockers (p = 0.04; OR 0.7), left atrium area 13 cm2 or
      greater (p = 0.02; OR 2.5), and peak atrial systolic mitral annular tissue
      Doppler velocity 9 cm/second or less (p = 0.03; OR 1.8) were independently
      related with the incidence of postoperative atrial fibrillation. CONCLUSIONS:
      Tissue Doppler is useful for assessing preoperative atrial dysfunction and
      predicting atrial fibrillation after CABG. Further studies are needed to confirm
      this finding.

PMID- 17184636
TI  - Ventricular epicardial lead placement for resynchronization by determination of
      paced depolarization intervals: technique and rationale.
AB  - BACKGROUND: Cardiac resynchronization therapy has been shown to be an effective
      treatment to improve functional status and prolong survival among patients with
      advanced congestive heart failure. However, as many as 30% of patients do not
      respond. Nonresponse may be due to suboptimal left ventricular lead placement.
      Studies have indicated that leads placed in the midlateral left ventricle (LV)
      wall usually result in improved dP/dT and increased pulse pressure, compared with
      other locations. When the surgeon is placing the leads thoracoscopically,
      however, in a chest with multiple adhesions, anatomic landmarks can be obscured.
      It is desirable to have an objective physiologic method to determine optimal lead
      placement. The optimal LV pacing site may be best determined by locating the site
      with the latest depolarization. METHODS: A pacing lead attached to a pulse
      analyzer was introduced through a thoracoscopic port and used as a mapping
      electrode to electrically map exposed areas of the left ventricle. The right
      ventricular pacing lead was also attached to the pulse analyzer and the interval
      between the right ventricular pulse and the LV depolarization (paced
      depolarization interval) was measured in 19 patients undergoing thoracoscopic LV
      lead placement. A site with a paced depolarization interval less than 110 ms was
      not accepted. RESULTS: Electrical mapping was possible in 19 of 29 consecutive
      patients in whom it was attempted. The most frequent reason for not mapping was
      the presence of extensive scarring. In 7 of 19 patients (36.8%) mapped, the site
      that would have been chosen by anatomic landmarks was not the site with the
      longest paced depolarization interval, and thus the lead placement was altered.
      CONCLUSIONS: The site with the longest paced depolarization interval is only
      selected 63.2% of the time when utilizing anatomic landmarks for placement.
      Nonresponse may be due to suboptimal LV lead placement. Measurement of paced
      depolarization intervals provides a physiologic method of determining optimal LV
      lead placement.

PMID- 17184637
TI  - Impact of diabetes on five-year outcomes of patients with multivessel coronary
      artery disease.
AB  - BACKGROUND: Diabetes mellitus is a major cause of coronary artery disease.
      Despite improvement in the management of patients with stable coronary artery
      disease, diabetes remains a major cause of increased morbidity and mortality.
      Although coronary artery bypass grafting surgery (CABG) and percutaneous coronary
      intervention are widely used, no conclusive evidence exists that either treatment
      modality is better than medical therapy alone for the treatment of stable single-
      or multivessel coronary disease in patients with diabetes. METHODS: We compared
      medical therapy, percutaneous coronary intervention, and CABG in 499 diabetic
      patients (38.5%) and 799 nondiabetic patients (61.5%) with single- or multivessel
      coronary disease. The composite primary endpoint was cardiac-related death, Q
      wave myocardial infarction, or refractory angina requiring revascularization.
      RESULTS: We treated 1,298 patients with either CABG (n = 524), percutaneous
      coronary intervention (n = 378), or medical therapy (n = 396). More deaths
      occurred among patients with diabetes than among patients without diabetes,
      regardless of which option was used (p < 0.001). When treatment modalities were
      stratified according to the number of diseased vessels, CABG was shown to be more
      beneficial for patients with diabetes and multivessel disease than for patients
      with diabetes and single-vessel disease (p < 0.001). However, when stratified by
      treatment, patients with diabetes receiving medical therapy had a worse prognosis
      than patients with diabetes treated with CABG (p = 0.005). CONCLUSIONS: All three
      therapeutic regimens resulted in high rates of cardiac-related deaths among
      patients with diabetes compared with patients without diabetes. Moreover, we
      observed better outcomes among patients with diabetes and multivessel coronary
      artery disease undergoing CABG regarding the primary endpoint at 5-year follow
      up.

PMID- 17184638
TI  - Is early too early? Effect of shorter stays after bypass surgery.
AB  - BACKGROUND: Postoperative stays after coronary artery bypass graft surgery (CABG)
      decreased substantially in the 1990s. Although shorter stays offer clinical
      benefits, premature discharge could increase adverse events and offset initial
      savings. This study examined the effect of early discharge after CABG on
      readmission/death and cost within 60 days of discharge home. Variability in
      hospitals' tendencies for early discharge and adverse outcomes was also explored.
      METHODS: Analyses were based on clinical and claims data for 55,889 New York CABG
      patients discharged home 1995 to 1998. Early discharge was defined as a
      postoperative stay below the 15th percentile for patients with similar risk. The
      likelihood of early discharge and its effect on readmission/death were examined
      using hierarchical logistic regression, accounting for patient risk and within
      hospital correlation. The correlation between early discharge and adverse
      outcomes at the hospital level was assessed. The effect of early discharge on
      subsequent inpatient, outpatient, skilled nursing, and home health costs was
      examined in the Medicare subset. RESULTS: Overall, 17% of patients were
      discharged early, with increasing prevalence over time. The tendency to discharge
      early varied widely among hospitals (2% to 42% of patients). We found no
      association between hospitals' tendencies for early discharge and adverse
      outcomes. Lower postdischarge costs among patients discharged early (mean = 3,491
      dollars versus 5,246 dollars for typical stays) resulted in average cumulative
      savings of 6,309 dollars. CONCLUSIONS: Patients selected for earlier discharge
      after CABG did not have increased adverse event rates or higher costs. Variation
      among hospitals in early discharge suggests that more efficient patient
      management could be achieved at some hospitals.

PMID- 17184639
TI  - Invited commentary.

PMID- 17184640
TI  - Seven-year follow-up after minimally invasive direct coronary artery bypass:
      experience with more than 1300 patients.
AB  - BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) for
      revascularization of the left anterior descending artery has become a routine
      operation. Here we present the experience after more than 1300 MIDCAB procedures
      with up to 7 years of follow-up. METHODS: All patients undergoing standard MIDCAB
      between 1996 and 2004 were included. Long-term follow-up information about health
      status, major cardiac and cerebral adverse events, and freedom of angina was
      collected annually by a questionnaire or personal contact. Preoperative,
      intraoperative, and postoperative data could be completed for all 1347 patients.
      Five-year follow-up was available for 450 patients and 7-year follow-up for 194
      patients. RESULTS: Mean age was 63.2 years (range, 25 to 92 years) and mean
      ejection fraction was 0.61 +/- 0.14. In 23 patients (1.7%), intraoperative
      conversion to sternotomy or CPB, or both, was necessary. Early postoperative
      mortality was 0.8% (n = 11), and 0.4% (n = 5) had a perioperative stroke. A
      routine postoperative angiogram in 709 patients showed 95.6% early graft patency.
      Short-term target vessel reintervention was needed 55 patients (4.1%): 10 had
      percutaneous transluminal coronary angioplasty/stent and 45 had reoperation. A
      repeat angiogram at the 6-month follow-up was available in 350 patients and
      demonstrated 94.3% graft patency. Kaplan-Meier analysis revealed a 5-year
      survival of 91.9% (95% confidence interval [CI], 90.1% to 93.8%) and a 7-year
      survival of 89.4% (95% CI, 86.7% to 92.1%). The freedom of major adverse events
      and angina was 89.5% (95% CI, 87.4% to 91.5%) after 5 years and 83.3% (95% CI,
      79.0% to 87.5%) after 7 years. CONCLUSIONS: MIDCAB can be safely performed with
      low postoperative mortality and morbidity. The excellent short-term and long-term
      survival as well as freedom from major adverse cardiac and cerebral events and
      angina compare favorably with stenting and conventional surgery.

PMID- 17184641
TI  - Early and midterm results of off-pump coronary artery bypass grafting.
AB  - BACKGROUND: Early outcomes of off-pump coronary artery bypass grafting have been
      documented by numerous studies. However, there have been few reports concerning
      midterm outcomes after off-pump coronary artery bypass grafting. METHODS: We
      retrospectively reviewed the records of 602 consecutive patients (24.8% female)
      who underwent isolated off-pump coronary artery bypass grafting between April
      2001 and July 2004. Mean age was 66.7 +/- 9.3 years. Mean Canadian Cardiovascular
      Society score was 2.5 +/- 0.9. Early postoperative angiograms were evaluated
      during the same period of hospitalization. Midterm outcomes, including overall
      patient survival, freedom from cardiac death, and freedom from the combined
      endpoint of cardiac events, were evaluated. RESULTS: The average number of distal
      anastomoses per patient was 3.6 +/- 1.4. The average operation time was 286.1 +/-
      72.1 minutes. Long segmental reconstruction of the left anterior descending
      coronary artery was performed in 218 patients (36.2%). Total arterial grafting
      was performed in 466 patients (77.4%). Thirty-day mortality was 0.5%. Overall
      patency rate for all grafts and anastomoses was 97.5% and 97.6%, respectively.
      Mean follow-up time was 2.9 +/- 1.0 years. Cumulative patient survival at 5 years
      was 87.9% +/- 2.4%. Freedom from cardiac death was 97.7% +/- 0.6% at 5 years.
      Freedom from the combined endpoint of cardiac events was 83.8% +/- 2.3% at 5
      years. CONCLUSIONS: Early and midterm outcomes after off-pump coronary artery
      bypass grafting have acceptable mortality and cardiac events rates, with
      favorable early graft patency rates.

PMID- 17184642
TI  - Angiographic fate of collateral vessels after surgical revascularization of the
      totally occluded left anterior descending artery.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) is best indicated for chronic
      total occlusion of the left anterior descending artery (LAD) with collaterals. We
      investigated angiographic changes in the collateral circulation after CABG.
      METHODS: Preoperative and postoperative angiograms were reviewed in 42 patients
      who underwent grafting onto occluded LADs. We described the type, location, and
      size of collaterals, the Rentrop grading, and collateral frame count (CFC).
      Regional wall motion of the LAD area was also evaluated with the centerline
      method. Postoperatively, we measured the lengths of LAD proximal (Lp) and distal
      (Ld) to the graft anastomotic site. RESULTS: Preoperative collaterals comprised
      78 pathways (septal 42%, branch-branch 20%, atrial 19%, bridging 18%). After
      CABG, residual collaterals were identified, mainly through the septal pathways,
      in 6 patients (14%), most of whom were diabetic. The residual collaterals were a
      part of those which had been opacified in earlier phases of the preoperative
      angiograms (CFC: 17 +/- 3 vs 25 +/- 15, p = 0.01). Also, the Ld was shorter in
      these patients so that Lp/Ld was greater than in patients without residual
      collaterals (0.80 +/- 0.24 vs 0.53 +/- 0.28, p = 0.04). We found no association
      of residual collaterals with the improvement of LAD regional wall motion after
      CABG. CONCLUSIONS: Even after successful CABG, some collaterals with earlier
      filling of the LAD remain, mainly through the septum. Although the clinical
      significance remains to be clarified, complex and diffuse atherosclerosis
      associated with more distal graft anastomoses may contribute to maintaining
      collaterals after CABG to the occluded LAD, especially in diabetic patients.

PMID- 17184643
TI  - Temperature changes stimulate contraction in the human radial artery and affect
      response to vasoconstrictors.
AB  - BACKGROUND: Radial artery conduits are increasingly used in coronary artery
      bypass grafting as an additional arterial graft to the internal thoracic artery.
      Their reactive nature remains a concern, often necessitating the routine use of
      topically applied vasodilators, such as glyceryl trinitrate, papaverine,
      phenoxybenzamine, or calcium channel antagonists, in theatre. During preparation
      prior to surgery and grafting, radial artery conduits are exposed to cooling and
      rewarming. We investigated how these temperature changes would affect radial
      artery contractility and how commonly used topical treatments might be used to
      prevent this. METHODS: Human radial artery was obtained excess to surgery and
      arterial sections used in organ bath tension experiments or for the culture of
      smooth muscle cells from medial explants. RESULTS: The radial artery responded to
      rapid cooling by the addition of 22 degrees C buffer with contraction. Gradual
      cooling, over a 20 to 30 minute period, reduced basal tension and the response to
      potassium chloride (KCl) and noradrenaline. Subsequent rewarming from 22 degrees
      C to 37 degrees C reestablished contraction at precooled levels and led to an
      elevation of the basal tension. Increases in tension measured in the radial
      artery were paralleled by increases in intracellular calcium in smooth muscle
      cells. Contraction induced by rapid temperature changes could be blocked by
      glyceryl trinitrate but not by phenoxybenzamine. Papaverine and calcium channel
      blockers had only limited activity. CONCLUSIONS: Temperature changes commonly
      encountered in theatre during the preparation of radial artery grafts are likely
      to cause contraction. If rapid temperature change cannot be avoided during graft
      preparation, then topically applied glyceryl trinitrate will block these
      responses.

PMID- 17184644
TI  - Invited commentary.

PMID- 17184645
TI  - Dose-related efficacy of aspirin after coronary surgery in patients With Pl(A2)
      polymorphism (NCT00262275).
AB  - BACKGROUND: To evaluate the impact of the genetic polymorphisms affecting aspirin
      response using platelet aggregation and the response to different aspirin doses
      after cardiopulmonary bypass, we performed a subanalysis of the results from a
      randomized trial evaluating low- and medium-dose aspirin and clopidogrel.
      METHODS: Blood was collected from consenting patients and DNA extracted.
      Polymerase chain reaction and restriction fragment length polymorphism analysis
      was performed to detect Pl(A2), C807T, and A842/C50T polymorphisms. Aspirin
      efficacy was assessed using light transmission platelet aggregometry, and
      reported as percentage aggregation and EC50 concentrations using the technique of
      Born. RESULTS: Of 90 patients, 80 consented to further genetic testing, of whom
      63 patients were randomly assigned to medium- (325 mg) or low-dose (100 mg)
      aspirin. The Pl(A2), C807T, and A842/C50T gene frequencies were 30%, 66%, and
      21%, respectively, with no identifiable differences in the baseline platelet
      aggregation. Postoperatively, after 5 days of aspirin, platelet aggregation was
      consistently but not significantly impaired with Pl(A2) and A842/C50T carriers
      and consistently but not significantly improved with C50T carriers. An
      interaction term was identified on percentage aggregation and EC50 using
      epinephrine. The interaction coefficient describes a higher aggregation of 19%
      (95% confidence interval: 2 to 36; p = 0.03) and less inhibition with an EC50 of 
      2.07 (-4.19 to 0.04; p = 0.06) in patients who were both Pl(A2) positive and
      receiving low-dose aspirin. CONCLUSIONS: Genetic polymorphisms that affect the
      response to aspirin are common. The impaired response of persons with the Pl(A2)
      polymorphism to aspirin may be dose related, with significant improvement
      observed in patients using medium- rather than low-dose aspirin.

PMID- 17184646
TI  - Invited commentary.

PMID- 17184647
TI  - Is extracorporeal life support contraindicated in elderly patients?
AB  - BACKGROUND: Extracorporeal life support (ECLS) using percutaneous extracorporeal
      membrane oxygenation (ECMO) is now considered an important means of resuscitation
      for patients suffering from refractory cardiogenic shock. The indications for the
      use of ECLS have yet to be established, however, and its use for elderly patients
      is still controversial. We retrospectively evaluated the impact of ECLS on the
      survival of patients with cardiogenic shock to determine the validity of using
      ECLS in elderly patients (> or = 75 years of age). METHODS: Between 2000 and
      2004, 91 patients were emergently placed on percutaneous ECMO. The patients were
      divided into two groups by age (group 1, n = 79: less than 75 years; group 2, n =
      12: 75 years or older), which were compared for clinical outcome. Logistic
      regression analysis of the variables was performed to identify predictors of
      ability to be weaned from ECLS. RESULTS: Weaning from ECLS was achieved in 50
      patients in group 1 (63.3%) and 6 patients in group 2 (50%; p = 0.37). Thirty
      five patients in group 1 (44.3%) and 5 patients in group 2 (41.7%) were
      discharged from the hospital (p = 0.86). Logistic regression analysis revealed
      that patients with a body surface area of more than 1.50 m2, patients with
      cardiomyopathy, and patients who underwent interventions under ECMO support were
      more likely to be successfully supported by ECMO. CONCLUSIONS: Extracorporeal
      life support using percutaneous ECMO systems provides excellent cardiac support.
      It is also effective in resuscitating elderly patients, yielding hospital
      survival similar to that for younger patients.

PMID- 17184648
TI  - Invited commentary.

PMID- 17184649
TI  - Leukocyte effects of C5a-receptor blockade during simulated extracorporeal
      circulation.
AB  - BACKGROUND: Distinct pathways of leukocyte activation during simulated
      cardiopulmonary bypass are mediated by the complement C5a anaphylatoxin. We
      hypothesized that a human C5a receptor antagonist would specifically inhibit the
      inflammatory response of neutrophils to simulated extracorporeal circulation,
      while preserving the C5b-9 pathway for innate immunity. METHODS: An in vitro
      extracorporeal circuit recirculated fresh heparinized whole blood through a
      membrane oxygenator with and without addition of a small molecule human C5a
      receptor antagonist. Samples were periodically drawn over 90 minutes for
      complement and leukocyte activation studies. RESULTS: Addition of the C5a
      receptor antagonist to simulated extracorporeal circulation abrogated both
      neutrophil CD11b upregulation and interleukin 8 release (p < 0.01 for both),
      despite full generation of C3a and C5b-9; however, elastase release from
      neutrophils was unaffected. Although C5a receptor blockade only trended toward
      inhibiting monocyte CD11b upregulation (p = 0.09), circuit clearance of both
      monocytes (p = 0.04) and neutrophils (p = 0.01) was significantly decreased. In
      addition, the C5a receptor antagonist completely blocked both neutrophil-platelet
      and monocyte-platelet conjugate formation (p < 0.001 for both), without affecting
      platelet P-selectin expression. CONCLUSIONS: C5a receptor blockade during
      simulated extracorporeal circulation completely blocked neutrophil beta2 integrin
      upregulation and induction of plasma interleukin 8, suggesting an acute
      downregulatory effect on neutrophil chemotaxis-related pathways, while preserving
      terminal complement generation and neutrophil elastase release. Inhibition of
      leukocyte-platelet conjugate formation suggests a novel function for leukocyte
      adhesive receptors, possibly related to preservation of elastase generation.

PMID- 17184650
TI  - Invited commentary.

PMID- 17184652
TI  - Invited commentary.

PMID- 17184651
TI  - Neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury after
      cardiopulmonary bypass in the rabbit endotoxemia model.
AB  - BACKGROUND: Neutrophil elastase probably contributes to the development of acute
      lung injury after cardiopulmonary bypass (CPB) in patients with infection or
      shock. We evaluated whether pretreatment with sivelestat sodium hydrate, a
      neutrophil elastase inhibitor (EI), can prevent acute lung injury caused by CPB.
      METHODS: Rabbits were assigned four groups: CPB for 60 minutes, control CPB
      group; low-dose lipopolysaccharide (LPS) administration without CPB, LPS group;
      CPB after lipopolysaccharide administration, LPS+CPB group; or preparation with
      continuous infusion of sivelestat and CPBs after lipopolysaccharide
      administration, EI group. Blood samples to determine blood gas concentration,
      plasma elastase activity, and plasma interleukin-8 levels were obtained.
      Histopathologic examinations of the lung were performed. RESULTS: The decreased
      arterial oxygen pressure at the end of CPB was observed in the LPS+CPB group
      only, but was suppressed in the EI group (p < 0.01). Elastase activity was
      markedly elevated at 120 minutes after CPB, and interleukin-8 levels were
      markedly elevated at 180 minutes in the LPS+CPB group but were much lower (p <
      0.05) in the EI group. Histopathology demonstrated accumulation of
      polymorphonuclear neutrophils in bronchoalveolar areas in the LPS+CPB group (p <
      0.01). Pulmonary myeloperoxidase activity was significantly lower in the LPS+CPB
      group than in the other groups (p < 0.01). These changes were minimal in the EI
      group. CONCLUSIONS: The combination of low dose LPS+60 minutes of CPB, but
      neither intervention alone, produced evidence of acute lung injury in a rabbit
      model. This did not occur when the animals were pretreated with sivelestat.

PMID- 17184653
TI  - Risk of surgery for congenital heart disease in the adult: a multicentered
      European study.
AB  - BACKGROUND: Surgery for congenital heart disease (CHD) has changed considerably
      during the last three decades. The results of primary repair have steadily
      improved, to allow treating almost all patients within the pediatric age;
      nonetheless an increasing population of adult patients requires surgical
      treatment. The objective of this study is to present the early surgical results
      of patients who require surgery for CHD in the adult population within a
      multicentered European study population. METHODS: Data relative to the hospital
      course of 2,012 adult patients (age > or = 18 years) who required surgical
      treatment for CHD from January 1, 1997 through December 31, 2004 were reviewed.
      Nineteen cardiothoracic centers from 13 European countries contributed to the
      data collection. RESULTS: Mean age at surgery was 34.4 +/- 14.53 years. Most of
      the operations were corrective procedures (1,509 patients, 75%), followed by
      reoperations (464 patients, 23.1%) and palliative procedures (39 patients, 1.9%).
      Six hundred forty-nine patients (32.2%) required surgical closure of an isolated
      ostium secundum atrial septal defect. Overall hospital mortality was 2%.
      Preoperative cyanosis, arrhythmias, and NYHA class III-IV, proved significant
      risk factors for hospital mortality. Follow-up data were available in 1,342 of
      1,972 patients (68%) who were discharged home. Late deaths occurred in 6 patients
      (0.5%). Overall survival probability was 97% at 60 months, which is higher for
      corrective procedures (98.2%) if compared with reoperations (94.1%) and
      palliations (86.1%). CONCLUSIONS: Surgical treatment of CHD in adult patients, in
      specialized cardiac units, proved quite safe, beneficial, and low-risk.

PMID- 17184654
TI  - Infant heart transplantation ten years later--where are they now?
AB  - BACKGROUND: Many uncertainties regarding the fate of children undergoing heart
      transplantation as infants were present when we and others embarked on this
      program. Although no truly long-term results are available, a significant cohort
      of children has now reached preteen and early teenage status. We reviewed our
      group of infants transplanted more than 10 years ago to assess survival and
      quality of life as they approach their teenage years. METHODS: We retrospectively
      reviewed the medical records of all infant (younger than 6 months of age) heart
      transplant recipients, transplanted between 1988 and 1995, to ascertain survival
      statistics, incidence of complications, and current health status. RESULTS: A
      total of 42 patients were identified. The majority of these underwent
      transplantation for hypoplastic left heart syndrome. Eleven patients have died, 4
      early and 7 late. The actual survival at 10 years is 76%. Twenty-seven of the 31
      long-term survivors attend regular school; 4 are in special education classes
      owing to developmental delay. Five patients take medication for attention-deficit
      disorder. Malignancies have been discovered in 5, and 1 died secondary to this.
      Six patients have significant renal insufficiency, 1 of whom has undergone renal
      transplantation. One patient has undergone retransplantation for coronary artery
      disease. One patient required reoperation for supravalvar aortic stenosis. Other
      general medical problems that are being treated include sleep apnea (n = 1),
      hypertension (n = 5), and recurrent pneumonias (n = 1). CONCLUSIONS: Although
      these children require ongoing medical attention, including daily medications and
      regular follow-up visits, most have a satisfactory quality of life and behave
      much like normal children.

PMID- 17184655
TI  - Surgery for transposition of the great arteries in neonates weighing less than
      2,000 grams: a consecutive series of 25 patients.
AB  - BACKGROUND: The arterial switch operation (ASO) is the optimal option for
      neonates with transposition of the great arteries (TGA). Low birth weight (LBW)
      and prematurity were considered as risk factors for poor outcome in early
      corrective surgery for cardiac defects. This retrospective study was undertaken
      to evaluate early and midterm results in infants with TGA weighing less than
      2,000 grams who underwent surgical procedure in the neonatal period. METHODS:
      Among the 1,505 patients who underwent surgical procedure for TGA at our
      institution, 25 (0.02%) had a birth weight less than 2,000 grams and constituted
      the study group. Median age at operation was 19 days and median weight was 1,930
      grams. Prior to surgery, all were in the intensive care unit. Eleven (48%) with
      TGA and intact interventricular septum had an ASO but one had a Senning
      operation. Among 13 patients (52%) with complex TGA, 9 had anatomic repair and 4
      had palliation. RESULTS: Operative mortality was 16%. Age at operation greater
      than 30 days and palliation were risks factors for early death. At postoperative
      43 months, actuarial survival rate was 71% and freedom from reoperation rate was
      73%. All survivors were considered to have good cardiac status; 95% joined the
      normal curve for LBW infants without heart defects. CONCLUSIONS: These data
      support that delaying repair in LBW neonates with simple or complex TGA does not
      confer any benefit and is associated with higher morbidity.

PMID- 17184656
TI  - Measurement of technical performance in congenital heart surgery: a pilot study.
AB  - BACKGROUND: Although adequacy of repair after congenital heart surgery is a
      crucial determinant of clinical outcome, there is no current method of
      assessment. We sought to develop a process to measure the adequacy of repair for
      a diverse group of congenital heart procedures. METHODS: Selected surgical
      procedures, consisting of repair of ventricular septal defect (VSD), tetralogy of
      Fallot (TOF), complete common atrioventricular canal (CAVC), and arterial switch
      operation, were divided into component subprocedures, each of which was assessed
      separately. Three outcome categories of "optimal," "adequate," and "inadequate"
      were defined by consensus according to postprocedure echocardiographic
      assessment. Outcome categories for conduction disturbance were also created. All
      patients undergoing one of the four procedures in 2004 were identified, and each
      subprocedure was assessed. Other clinical data were obtained from medical
      records. Repairs were scored as "optimal" if all attempted subprocedures and
      conduction were optimal, and "inadequate" if any was inadequate. RESULTS: A total
      of 138 procedures were included. VSD repair was done in 46 patients (33%), TOF
      repair in 33 (24%), arterial switch operation in 36 (26%), and CAVC repair in 23
      (17%). Optimal technical score was found in 28 (20%), adequate in 106 (77%), and
      inadequate in 4 (3%) (2 VSD, 1 TOF, 1 CAVC). Median length of stay was 8 days,
      and no patients died. CONCLUSIONS: Despite procedural diversity and complexity,
      technical adequacy of repair can be assessed for congenital heart surgery.

PMID- 17184657
TI  - Right ventricular outflow tract reconstruction with contegra monocuspid
      transannular patch in tetralogy of Fallot.
AB  - BACKGROUND: Pediatric diminutive right ventricular outflow tract (RVOT)
      reconstruction with homografts or porcine xenografts remains challenging because
      of limited availability, early degeneration, tissue ingrowth, and child growth.
      The objective of this study was to assess whether Contegra valved bovine conduit,
      implanted as monocuspid transannular patch, might be an interesting alternative
      to overcome these problems. METHODS: We reconstructed the RVOT of 12 patients
      with tetralogy of Fallot, by the use of a Contegra conduit, tailored as a
      monocuspid valved transannular patch. The patients were 4 females and 8 males,
      with a mean age of 12.8 +/- 15.1 months and a mean weight of 7.2 +/- 1.9 kg. The
      mean pulmonary artery annulus size was 8.2 +/- 1.6 mm. RESULTS: The Contegra
      tissue was suitable for suturing and for reconstruction of even severely
      hypoplasic RVOT. We did not observe any sign of conduit or valve degeneration
      during the follow-up of 28.1 +/- 17.1 months. There were no early or late deaths,
      and no device-related adverse events. A peak transvalvular gradient of 36.5 +/-
      4.7 mm Hg was measured by echocardiography in 4 patients postoperatively, and it
      decreased during the follow-up to 20 +/- 7.6 mm Hg. Pulmonary valve incompetence
      was grade 3 in 2 patients and grade 4 in 2 patients. CONCLUSIONS: The Contegra
      monocuspid transannular patch is widely applicable to RVOT reconstruction with
      satisfactory midterm results, particularly in patients with small pulmonary
      annulus. Its main advantage is to reduce the potential risk of supravalvular
      stenosis due to the narrowing at the distal suture line, as demonstrated when
      used as conduits, especially in the smaller sizes.

PMID- 17184658
TI  - Pulmonary arterial reconstruction for pulmonary coarctation in early infancy.
AB  - BACKGROUND: Pulmonary atresia with pulmonary coarctation may complicate
      diminished and unbalanced pulmonary development. The aim of this study is to
      assess the outcome of pulmonary arterial reconstruction with cardiopulmonary
      bypass in early infancy for sufficient and balanced pulmonary development.
      METHODS: We performed a retrospective review of 15 patients with pulmonary
      coarctation younger than 4 months of age who underwent pulmonary arterial
      reconstruction between 2001 and 2005. The mean age and weight were 42.2 days and
      3.62 kg, respectively. The patient population included 5 biventricular repair
      candidates and 10 Fontan candidates. To evaluate the pulmonary arterial
      development, the preoperative and postoperative pulmonary arterial index and
      minimum diameter of the pulmonary artery were compared. RESULTS: No early or in
      hospital deaths occurred, and there was no nonconfluent pulmonary artery
      development or segmental mal-development after a mean follow-up period of 14.9
      months. Immediate pulmonary flow regulation was required in 2 patients because of
      excessive pulmonary flow. The mean pulmonary arterial index increased
      significantly from 103 mm2/m2 to 343 mm2/m2, and the mean minimum diameter of the
      pulmonary artery increased significantly from 2.02 mm to 4.45 mm. Four
      biventricular repair candidates completed definitive repair, and 2 required
      surgical reintervention in the pulmonary artery. Six Fontan candidates completed
      the Glenn procedure, and 1 completed the Fontan procedure. Three required
      surgical reintervention in the pulmonary artery. Two late deaths occurred after
      the Glenn procedure because of ventricular dysfunction and respiratory infection.
      CONCLUSIONS: Pulmonary arterial reconstruction in early infancy provides
      sufficient and balanced pulmonary arterial development for pulmonary atresia with
      pulmonary coarctation.

PMID- 17184659
TI  - Routine evaluation for aspiration after thoracotomy for pulmonary resection.
AB  - BACKGROUND: The purpose of this study was to evaluate the role of a routine
      protocol for evaluation of oropharyngeal aspiration after thoracotomy for
      pulmonary resection. METHODS: Demographic, operative, and outcomes data were
      collected prospectively for consecutive patients undergoing thoracotomy for
      pulmonary resection starting in April 2005. Starting on postoperative day one,
      patients underwent evaluation by a licensed speech therapist before per os
      intake. Patients failing clinical examination were referred for radiographic
      evaluation. Diets were advanced on the basis of results from both clinical and
      radiographic evaluation. Data analysis included descriptive statistics, Student's
      t test, and chi2 test when appropriate. RESULTS: One hundred forty patients were
      prospectively evaluated during this period. Thirty-two patients (22.9%) failed
      initial clinical swallowing evaluation and were referred for dynamic
      videofluoroscopic esophagram. Twenty-five patients (17.8%) had evidence of
      potential oropharyngeal aspiration on videofluoroscopic esophagram. Only 1
      patient (0.7%) aspirated after a negative clinical evaluation. Univariate risk
      factor analysis revealed that patients demonstrating aspiration were older (67.7
      +/- 1.6 years versus 64.4 +/- 1.1 years; p = 0.10) and had a higher incidence of
      head and neck malignancy (p < 0.001). Patients without radiographic aspiration
      had a shorter median hospital stay when compared with those who did (6 days
      versus 5 days). CONCLUSIONS: Aspiration after thoracotomy for pulmonary resection
      may affect nearly 20% of patients and is likely underrepresented in the surgical
      literature. The institution of a protocol to evaluate risk of aspiration has
      characterized patients at high risk and led to an increased awareness of the
      potential for aspiration after thoracotomy.

PMID- 17184660
TI  - Invited commentary.

PMID- 17184661
TI  - Recurrence patterns in patients with early stage non-small cell lung cancers
      undergoing positive pleural lavage cytology.
AB  - BACKGROUND: Cytologic approaches such as pleural lavage cytology (PLC) are
      considered as possible aids to assessing prognosis of lung cancers. However,
      there is some controversy whether radical surgery is warranted based on the
      positive PLC findings with stage I non-small cell lung cancers (NSCLCs). METHODS:
      From January 1991 to December 2002, PLC was performed before any manipulation or
      resection of the lung for 853 consecutive patients who had no macroscopic pleural
      effusion, dissemination, or diffuse adhesions and who subsequently underwent
      curative resection for NSCLCs. Results of PLC with reference to clinicopathologic
      characteristics, adjuvant therapy, 5-year survival, and recurrence patterns were
      analyzed. RESULTS: PLC findings were positive in 41 patients (4.8%), rates being
      most frequent with adenosquamous carcinomas and adenocarcinomas. In the positive
      group, distant metastases (72%) and pleural recurrence (25%) (p = 0.0011) were
      often observed, and the survival rate was significantly poorer (p < 0.002), even
      for patients with stage I disease (p = 0.009). As adjuvant therapies in the
      positive group after resection, 6 patients received hypotonic cisplatin and 15
      received a distilled water infusion into the pleural space. Although only 2
      patients had pleural recurrence, these therapies did not improve long-term
      outcome. CONCLUSIONS: PLC is a distinct prognostic factor for early stage lung
      carcinomas. Thus, we suggest that cytologic examination of PLC should be routine,
      even for patients with stage I NSCLCs before beginning lung resection. Moreover,
      curative resection, followed by adjuvant systemic therapy, could be necessary for
      improvement of outcome.

PMID- 17184662
TI  - Invited commentary.

PMID- 17184663
TI  - Clinical relevance of intraoperative pleural lavage cytology in non-small cell
      lung cancer.
AB  - BACKGROUND: Intraoperative pleural lavage cytology for patients with lung cancer
      has been reported to be useful in detecting subclinical pleural dissemination.
      However, this procedure is not necessary for the staging of lung cancer in the
      current TNM staging system. METHODS: Clinical records of 1025 patients with non
      small cell lung cancer who underwent surgery were retrospectively reviewed and
      evaluated for the clinical relevance of intraoperative pleural lavage cytology.
      RESULTS: Specimens of 37 patients (3.6%) were positive for pleural lavage
      cytology (PLC). Patients were categorized into three groups: positive PLC group,
      27 patients with positive PLC without malignant pleural effusion or pleural
      dissemination; pleural dissemination (PD) group, 21 patients with malignant
      pleural effusion or PD; negative PLC group, 977 patients with negative PLC or
      negative PLC without PD. The positive PLC group had a significantly higher ratio
      of adenocarcinomas than the negative PLC group (p = 0.014). There was a
      significant difference in distribution of pleural factors between the positive
      and negative PLC groups (p < 0.001). Survival in the positive PLC group was
      significantly worse than in the negative PLC group (p = 0.007), especially in
      pathologic stage I (p = 0.001), but significantly better than in the PD group (p
      = 0.038). PLC status was found to be a significant independent prognostic factor
      in the multivariate analysis (p = 0.016). CONCLUSIONS: The present study
      demonstrates the clinical relevance of intraoperative PLC in early stage non
      small cell lung cancer. The result of intraoperative PLC should be involved in
      the staging system of lung cancer.

PMID- 17184664
TI  - Prognostic significance of a histologic subtype in small adenocarcinoma of the
      lung: the impact of nonbronchioloalveolar carcinoma components.
AB  - BACKGROUND: We tried to clarify whether the histologic subtypes and the size of
      the solid component of an adenocarcinoma are more important predictive factors
      for invasiveness or prognosis than is total tumor size, even in lung
      adenocarcinomas that were 2 cm or smaller. METHODS: Between 1996 and December
      2005, after standard surgical treatment, 82 patients were diagnosed as having
      adenocarcinoma with a maximum diameter of 2 cm or less. The group comprised 37
      females and 45 males, with ages ranging from 41 to 80 years (median, 64). The
      clinicopathologic records of the patients were examined with regard to age, sex,
      nodal status, tumor size (largest diameter of the total tumor as well as the
      largest diameter without the bronchioloalveolar carcinoma [BAC] component [solid
      component]), serum carcinoembryonic antigen level, and histologic type. These
      variables were analyzed as risk factors for vascular or lymphatic invasion, lymph
      node metastasis, and prognosis. Histologic subtype was classified into two
      groups: mixed BAC (mixed adenocarcinoma with BAC) and minimal or non-BAC (tumors
      with little or no BAC component). RESULTS: Histologic subtype was a significant
      predictive factor both for invasiveness (vascular or lymph vessels) and lymph
      node metastasis, in both univariate and multivariate analysis. Tumor diameter was
      not a significant factor in either univariate or multivariate analysis (p = 0.28,
      0.15, respectively). However, diameter excluding the BAC component was a
      significant factor for invasiveness in mixed BAC type (p = 0.035), whereas total
      diameter was not significant (p = 0.28). Finally, histologic subtype and lymph
      node metastasis were significant prognostic factors for survival in both
      univariate (p = 0.03, 0.05, respectively) and multivariate (p = 0.04, 0.05,
      respectively) analyses. The 5-year survival rate was 94.4% (94.1% for pN0) for
      the mixed BAC type and 71.4% (78.7% for pN0) for the minimal or non-BAC type (p =
      0.009; p = 0.04 for pN0 nodes). CONCLUSIONS: Small adenocarcinomas can be
      classified into two categories. The first category is a minimal or non-BAC
      adenocarcinoma that shows aggressive biological behavior. The second category is
      a mixed BAC, which demonstrates less invasive or aggressive biological behavior
      than the minimal or non-BAC type, with the degree of invasiveness being
      associated with the size of the non-BAC component.

PMID- 17184665
TI  - Invited commentary.

PMID- 17184666
TI  - Clinical value of serum cytokeratin 19 fragment and sialyl-Lewis x in non-small
      cell lung cancer.
AB  - BACKGROUND: This study aimed to establish the clinical significance of
      preoperative serum cytokeratin 19 fragment (CYFRA21-1) and sialyl-Lewis x (SLex)
      as prognostic markers. METHODS: The study involved 272 patients (181 male, 91
      female; median age 69 years; range, 32 to 92) with non-small cell lung cancer
      (NSCLC) who underwent pulmonary resection with mediastinal lymph node dissection.
      Tumor markers carcinoembryonic antigen (CEA), squamous cell carcinoma antigen
      (SCC), CYFRA21-1, and SLex were examined. RESULTS: A log-rank test revealed that
      age, gender, performance status, CEA, SCC, CYFRA21-1, and SLex were associated
      with the survival rate. By multivariate analysis, age, gender, performance
      status, CYFRA21-1 (risk ratio, 2.42) and SLex (risk ratio, 6.18) were independent
      prognostic factors. For patients positive for both markers, the relative risk was
      6.10 compared with patients negative for both markers. The patients were divided
      into three groups: negative for both CYFRA21-1 and SLex (n = 97); positive for
      either marker (n = 136); and positive for both markers (n = 39). The 1-, 3-, and
      5-year survival rates were the following: 98%, 82%, and 75% in the first group;
      90%, 63%, and 49% in the second group; and 62%, 31%, and 25% in the third group
      (p < 0.001). Sixty-four percent of patients positive for both markers were
      histologic stage III/IV, and 68% of patients negative for both markers were stage
      I. CONCLUSIONS: Serum CYFRA21-1 and SLex were prognostic markers for NSCLC. Their
      combination should contribute to the classification of NSCLC patients.
      Preoperative staging should be carefully performed in patients positive for both
      tumor markers.

PMID- 17184667
TI  - Invited commentary.

PMID- 17184668
TI  - Superior vena cava resection for lung and mediastinal malignancies: a single
      center experience with 70 cases.
AB  - BACKGROUND: The oncologic value of superior vena cava (SVC) resection for lung
      and mediastinal malignancies remains controversial. In this context, we have
      reviewed our experience in the treatment of locally advanced lung and mediastinal
      tumor invading the SVC system, analyzing postoperative outcome and long-term
      oncologic results. METHODS: The clinical data of patients who underwent SVC
      resection were retrospectively analyzed to assess postoperative mortality, and
      overall and procedure-specific morbidity. Overall survival was calculated for
      mediastinal and lung tumor groups. RESULTS: From 1998 to 2004, 70 consecutive
      patients (52 with lung cancer and 18 with mediastinal tumors) underwent SVC
      system resection. There were 25 replacements (36%) of the SVC system by
      prosthesis, whereas the remaining underwent partial resection. Major
      postoperative morbidity and mortality rates in lung cancer patients were 23% and
      7.7%, respectively (50% and 5.6% in mediastinal tumors). In the lung cancer
      group, 5-year survival probability was 31%, and it was affected by mediastinal
      nodal status (5-year survival in N0-N1 patients 52%, 21% in N2 patients, 0 in N3
      patients). Median survival for mediastinal tumors was 49 months. CONCLUSIONS: In
      conclusion, SVC resection may achieve permanent cure in patients who would have
      been defined as inoperable 10 years ago. In the case of mediastinal tumors, the
      need for SVC resection alone should not be considered a contraindication for
      surgery when prosthetic replacement is feasible. In the case of lung tumors,
      infiltration of SVC can achieve satisfactory long-term results after neoadjuvant
      chemotherapy, only when pathologic N2 disease is excluded by preoperative
      mediastinoscopy.

PMID- 17184670
TI  - Invited commentary.

PMID- 17184669
TI  - Oligometastatic non-small cell lung cancer: a multidisciplinary approach in the
      positron emission tomographic scan era.
AB  - BACKGROUND: We have assessed the survival rate of patients with non-small cell
      lung cancer and synchronous hematogenous solitary metastasis identified with
      complete staging workup, including total body [18F]fluorodeoxyglucose positron
      emission tomography scan, and treated with a multidisciplinary approach. METHODS:
      We examined the database of all patients who underwent surgery for primary non
      small cell lung cancer in our institute. The criteria required for inclusion in
      this analysis were diagnosis of non-small cell lung cancer with synchronous
      hematogenous solitary metastasis by staging workup with total body computed
      tomography scan and brain magnetic resonance if indicated, total body positron
      emission tomography scan, radical surgery for the primary tumors, local treatment
      of the solitary metastasis, and systemic chemotherapy administration. RESULTS: We
      analyzed the data from 1,509 patients treated from January 2000 to December 2005:
      10 patients (0.7%) satisfied the selection criteria. The median overall survival
      was 26 months, and the median time to progression was 20 months; 6 patients were
      alive at the time of analysis, with a median follow-up of 30 months. Four
      patients were tumor progression-free after 9, 18, 23, and 32 months from the
      start of their treatment. CONCLUSIONS: The presentation of non-small cell lung
      cancer with a synchronous hematogenous solitary metastasis identified by
      [18F]fluorodeoxyglucose positron emission tomography containing complete staging
      workup is extremely rare. This subset of patients can achieve long-term survival
      after a multidisciplinary treatment approach.

PMID- 17184671
TI  - Role of surgery in the treatment of primary pulmonary B-cell lymphoma.
AB  - BACKGROUND: The purpose of this study was to define the role of surgery in the
      treatment of primary pulmonary lymphoma (PPL). METHODS: We reviewed all patients
      presenting with a pathologic diagnosis of PPL in our institution during the past
      20 years. We analyzed the outcome and determined the impact of complete versus
      incomplete surgical resection on survival. RESULTS: The study included 17
      patients with PPL confined to the pulmonary parenchyma. Pathologic diagnosis was
      low-grade B-cell PPL in 14 patients, high-grade B-cell PPL in 2, and lymphomatoid
      granulomatosis in 1. A complete resection was performed in 8 patients presenting
      with low-grade B-cell PPL and in 2 patients with high-grade B-cell PPL. The
      overall survival of patients presenting with low-grade B-cell PPL was 63% at 10
      years; however, survival at 10 year tended to be better when a complete resection
      was performed (87.5% vs 25%, respectively; p = 0.08). Gender, bilateral disease,
      or adjuvant therapy did not affect survival. Both patients presenting with high
      grade B-cell PPL are alive and free of disease 22 and 36 months after the
      surgery, respectively. The patient presenting with lymphomatoid granulomatosis is
      alive after 2 years of follow-up. CONCLUSIONS: PPL is a rare disease that may be
      localized or diffuse in one or both lungs. Surgery should be the treatment of
      choice in the localized form of PPL if complete resection can be achieved. A
      complete resection is associated with an excellent long-term survival of almost
      90%. If the lesions are diffuse or involve both lungs, medical therapy should
      then be the treatment of choice.

PMID- 17184673
TI  - Cytokine response is lower after lung volume reduction through bilateral
      thoracoscopy versus sternotomy.
AB  - BACKGROUND: Lung volume reduction surgery performed through bilateral video
      assisted thoracoscopy (BVATS) was associated in the National Emphysema Treatment
      Trial with a statistically significant reduction in intensive care unit days,
      failure to wean, hospital stay, and cost, and earlier recovery compared with
      median sternotomy. Studies comparing other minimally invasive techniques with
      "open" procedures, including pulmonary lobectomy, have demonstrated reduced serum
      proinflammatory mediators postoperatively. We measured these levels after lung
      volume reduction surgery through BVATS and sternotomy. METHODS: Serum cytokine
      levels were measured by radioimmunoassay in 9 consecutive, steroid-free patients
      undergoing sternotomy and lung volume reduction surgery and 6 undergoing BVATS
      and lung volume reduction surgery. The groups were not statistically different
      with respect to age, partial pressure of arterial carbon dioxide, percent forced
      expiratory volume in 1 second, percent residual volume, percent total lung
      capacity, diffusion capacity of the lung for carbon monoxide, 6-minute walk, or
      apical perfusion fraction. Proinflammatory interleukin 6 and interleukin 8 and
      antiinflammatory interleukin 10 were evaluated preoperatively and postoperatively
      on days 1, 4, and 5. Clinical data were prospectively collected. RESULTS: There
      were no major postoperative complications or deaths. Interleukin 6 levels were
      lower in the BVATS than the sternotomy group (p = 0.016 by repeated measures
      analysis of variance). Interleukin 8 levels were lower in the BVATS group at most
      postoperative time points, but there were no significant differences in
      interleukin 8 or interleukin 10 levels between the sternotomy and BVATS groups at
      any individual time point or by analysis of variance. CONCLUSIONS: Use of a BVATS
      approach to lung volume reduction surgery is associated with reduced
      postoperative release of proinflammatory cytokines compared with a sternotomy
      approach. This may account for the reduction in recovery time and some measures
      of postoperative morbidity seen with the BVATS approach.

PMID- 17184674
TI  - Feasibility and utility of a lung donor score: correlation with early post
      transplant outcomes.
AB  - BACKGROUND: A lung donor score may provide a numerical value of overall donor
      lung "quality" to allow comparison among different organizations and research
      protocols. This study aims to develop a simple scoring system and investigate its
      applicability on predicting donor selection and early post-lung-transplant (LTx)
      outcomes. METHODS: Data of all donors referred to our institution in 2001 were
      initially analyzed to create a LTx donor score. Five domains, age, smoking
      history, chest X-ray, secretions, and arterial blood gas results, were included.
      A larger cohort of transplant recipients (years 2002 to 2005) was analyzed to
      validate the score against early post-LTx outcomes. RESULTS: In the initial 2001
      cohort, 36 of 87 (41%) donors were used for 41 LTx (used group) and 51 (59%) were
      declined for medical (lung-exclusion group, n = 31) and general (general
      exclusion group, n = 20) reasons. The median donor scores in the used, general
      exclusion, and lung-exclusion groups were 2.0, 2.0, and 10.0, respectively (p <
      0.0001). In multivariate analysis of the validation cohort, the donor score in
      bilateral LTx was significantly associated with post-transplant ratio of arterial
      oxygen tension and inspired oxygen fraction (coefficient = -16.19, p = 0.002),
      primary graft dysfunction grade (coefficient = 0.21, p < 0.0001), and intubation
      hours (coefficient = 0.05, p = 0.04); however, a significant association was not
      seen in single LTx. CONCLUSIONS: A proposed simple donor scoring system, based on
      five major donor variables available at the time of donor selection, may be
      useful for data comparison between specific centers, quality control, evaluative
      research, and clinical decision making in donor selection and management in LTx.

PMID- 17184675
TI  - Invited commentary.

PMID- 17184676
TI  - Intrathoracic periesophageal fundoplication for short esophagus: a 20-year
      experience.
AB  - BACKGROUND: Intrathoracic periesophageal fundoplication carries a high risk of
      treacherous technical complications such as spontaneous gastric perforation.
      METHODS: An intrathoracic fundoplication was performed on 84 patients suffering
      from gastroesophageal reflux disease with the junction between upper gastric
      folds and the unwrinkled esophageal mucosa remaining above the diaphragm while
      the esophageal body was quite straight on barium swallow study. Particular
      attention was paid to the following steps: further enlargement of the hiatal
      sling to avoid any strangulation of the stomach, very careful manipulation of
      gastric tissues with the fingers rather than with forceps, and meticulous
      anchoring of the wrap to the hiatus with numerous sutures while mimicking
      diaphragmatic movements that arise on cough. Results were assessed by personal
      interview (n = 84; median follow-up, 51.5 months), barium swallow study (n = 84),
      24-hour esophageal pH monitoring (n = 65), and esophageal stationary manometry (n
      = 56). RESULTS: No patient had any symptoms of reflux; 5 (5.9%) had episodes of
      dysphagia, which were frequent in 2; and 31 (37%) had some degree of flatulence,
      which interfered with social life in 5. The mean percentage of total time that
      esophageal pH was below 4 at esophageal pH monitoring dropped significantly (p <
      0.001) from 12.3% before fundoplication to 0.5% after. Lower esophageal sphincter
      resting pressure increased significantly (p < 0.0001) from 6.9 mm Hg to 20.6 mm
      Hg. Nine patients (10.7%) were reoperated on for spontaneous (n = 1) or anti
      inflammatory drug-induced (n = 1) gastric perforation, further herniation of the
      stomach (n = 3), herniation of the colon (n = 3), or both (n = 1), into the
      chest. CONCLUSIONS: Intrathoracic periesophageal fundoplication for short
      esophagus is amazingly effective for treating reflux. Strict observance of some
      critical technical details makes spontaneous gastric perforation very unlikely.
      Any sudden increase in abdominal pressure at early follow-up is to be avoided,
      and anti-inflammatory drugs are strictly forbidden.

PMID- 17184678
TI  - Arrow CorAide left ventricular assist system: initial experience of the cardio
      thoracic surgery center in Pavia.
AB  - PURPOSE: The aim of the present study is to describe our preliminary experience
      with the Arrow CorAide left ventricular assist system (LVAS). DESCRIPTION: The
      Arrow CorAide LVAS is a small implantable, continuous flow centrifugal pump, with
      a fully suspended rotating assembly, intended as a bridge to transplant device,
      bridge to recovery, and for long-term use. EVALUATION: Since April 2005 we have
      implanted the CorAide LVAS in 2 male patients, with a patient follow-up of more
      than 6 months. Surgical procedures were uneventful, and both patients had an
      uneventful postoperative course, with fast weaning from mechanical ventilation
      and inotropic support. No thromboembolic events, infective complication,
      hemolysis, or mechanical failure occurred. To date, both patients are in New York
      Heart Association class I. CONCLUSIONS: In our initial experience the CorAide
      LVAS blood pump is nonthrombogenic, nonhemolytic, and easy to implant. Both
      patients have improved their functional status. Further follow-up is needed to
      assess long-term results.

PMID- 17184677
TI  - Introduction to thoracic endografting: imaging, guidewires, guiding catheters,
      and delivery sheaths.
AB  - PURPOSE: With the recent approval of the first thoracic endoprosthesis in the
      United States for the treatment of isolated descending thoracic aortic aneurysms,
      there has been a dramatic increase in the number of physicians interested in
      getting involved in this emerging technology. However, many of these physicians
      do not have extensive endovascular experience, are not familiar with the
      catheters and guidewires used for thoracic endografting procedures, or do not
      have access to a full complement of endovascular resources. DESCRIPTION: We
      discuss the basics of catheters, guidewires, and balloons necessary to perform
      thoracic endovascular procedures. EVALUATION: Adequate radiographic visualization
      of the thoracic aorta and access vessels is essential for all phases of the
      thoracic endografting procedure. In addition, a vast array of catheters,
      guidewires, balloons, and sheaths have been designed to assist with endovascular
      access and delivery of various therapeutic modalities. CONCLUSIONS: Each of the
      different catheters and guidewires serve an important purpose in the conduct of
      thoracic endografting procedures, and it is important to have a full
      understanding of these devices to ensure the best results.

PMID- 17184679
TI  - Invited commentary.

PMID- 17184680
TI  - Can a falling bullet be lethal at terminal velocity? Cardiac injury caused by a
      celebratory bullet.
AB  - This is a case report of rare cardiac and abdominal organ injuries sustained by
      an innocent bystander from a New Year's Eve celebratory gun shooting. The force
      and velocity of a projectile fired into the air as it ascends and returns to
      earth, along with its potential for bodily injury will be reviewed.

PMID- 17184681
TI  - Implantation of the CoreValve percutaneous aortic valve.
AB  - Surgical aortic valve replacement is the only recommended treatment for
      significant aortic valve stenosis. Percutaneous aortic valve replacement appears
      to be a novel option for high-risk patients. We report the implantation of the
      ReValving system (CoreValve, Paris, France) in a 64-year-old woman who was
      refused aortic valve replacement surgery for critical aortic stenosis and left
      ventricular dysfunction because of severe pulmonary fibrosis. After anesthesia,
      the patient was put on femorofemoral cardiopulmonary bypass, and underwent a
      balloon valvuloplasty with subsequent retrograde aortic valve replacement by the
      ReValving system. Transesophageal echocardiographic monitoring of the patient's
      hemodynamics showed immediate improvements of the valvular area and left
      ventricular ejection fraction and only traces of paravalvular leaks. The patient
      was easily weaned from ventilation and resumed activity soon after the surgery. A
      multidisciplinary approach is presently necessary to offer a reliable and safe
      procedure.

PMID- 17184682
TI  - Successful aortic valve replacement for Heyde syndrome with confirmed hematologic
      recovery.
AB  - Aortic valve stenosis can be complicated by recurrent gastrointestinal bleeding,
      particularly that due to angiodysplasia, also called Heyde syndrome. Recently,
      acquired type 2A von Willebrand disease, which is characterized by the loss of
      the large multimer of von Willebrand factor by the shear stress of aortic valve
      stenosis, was reported to be associated with this hemorrhagic syndrome. A 78-year
      old woman, with severe aortic stenosis, presented with advanced anemia due to
      recurrent gastrointestinal bleeding and was diagnosed Heyde syndrome. By
      perioperative supplementation of von Willebrand factor and factor VIII, aortic
      valve replacement was safely performed without gastrointestinal bleeding. After
      the operation, the multimer of von Willebrand factor was normalized and
      thereafter no gastrointestinal bleeding occurred. This case reports the
      successful aortic valve replacement for Heyde syndrome, with confirmed
      hematologic recovery.

PMID- 17184683
TI  - Concomitant traumatic aortic valve and coronary artery injury.
AB  - A 79-year-old man, who had sustained nonpenetrating chest trauma 1 month
      previously, was admitted for dyspnea. Echocardiography demonstrated prolapse of
      the noncoronary aortic cusp with severe regurgitation. Aortography showed no
      intimal flap in the ascending aorta. Coronary arteriography showed dissection
      extending from the left main trunk to the proximal circumflex artery. At surgery,
      no abnormalities were found in the aortic wall or around the left coronary
      ostium. Avulsion of the commissure between the right coronary cusp and the
      noncoronary cusp from its aortic wall attachment was detected. Aortic valve
      replacement and coronary artery bypass grafting were performed.

PMID- 17184684
TI  - Surgical treatment of bilateral aneurysmal coronary to pulmonary artery fistulas
      associated with severe atherosclerosis.
AB  - A 39-year-old diabetic patient with an old inferior wall infarction presented
      with disabling angina pectoris, despite medical treatment. Coronary angiography
      showed severe triple-vessel coronary artery disease, and bilateral coronary to
      pulmonary fistulas originating from the right coronary artery and the left
      anterior descending coronary artery. Both coronary artery saphenous vein bypass
      grafting and ligation of the fistulas was performed.

PMID- 17184685
TI  - Temporary perfusion for mesenteric ischemia with acute type A aortic dissection.
AB  - We report advantages of a temporary mesenteric perfusion method for bowel
      ischemia with acute type A aortic dissection. The perfusion catheter was inserted
      from the branch of the superior mesenteric artery. This technique was found to be
      useful in certain cases that require prompt visceral organ perfusion and proximal
      aortic repair, which enabled a simultaneous treatment for both lesions and a
      blood pressure evaluation.

PMID- 17184687
TI  - Bi-ventricular circulatory support with the Abiomed AB5000 system in a patient
      with idiopathic refractory ventricular fibrillation.
AB  - A 45-year-old man had life-threatening recurrent idiopathic ventricular
      fibrillation and persistent cardiogenic shock develop. The episodes of
      ventricular fibrillation were refractory to aggressive medical management;
      therefore an Abiomed AB5000 bi-ventricular support system was implanted for
      arrhythmia control. The device was able to maintain hemodynamic stability during
      the following 2 weeks. The patient was discharged from the hospital with fully
      recovered cardiac function.

PMID- 17184686
TI  - Takotsubo cardiomyopathy: expanding the differential diagnosis in cardiothoracic
      surgery.
AB  - We describe a case of takotsubo cardiomyopathy in a 69-year-old woman after right
      upper lobectomy, without cardiac antecedents. The immediate course of recovery
      was uneventful. On the first postoperative day, clinical symptoms of acute
      coronary syndrome developed in association with ischemic electrocardiographic
      changes and a mild elevation in creatinine phosphokinase levels. Echocardiography
      showed moderate left ventricular dysfunction, with a typical takotsubo pattern.
      Coronary angiography revealed no abnormalities. After 2 days of supportive
      treatment, the patient recovered completely. The clinical presentation,
      instrumental findings, additional cardiac and noncardiac diseases, and the
      potential pathomechanism of takotsubo cardiomyopathy are described according to
      the current medical literature.

PMID- 17184688
TI  - Thoracoscopic microwave epicardial ablation: feasibility for the treatment of
      idiopathic sinus node tachycardia.
AB  - Inappropriate sinus tachycardia is a potentially debilitating condition with
      tachycardia emanating from the sinus node region. Endocardial radiofrequency
      energy ablation is the current preferred mode of treatment for symptomatic
      medication failures. Phrenic nerve damage can result from this procedure. We
      report a case in which the potential for phrenic nerve damage was avoided by
      using a thoracoscopic approach to displace the phrenic nerve posteriorly and
      perform epicardial microwave ablation. This resulted in the successful treatment
      of a patient with highly symptomatic inappropriate sinus tachycardia.

PMID- 17184689
TI  - Preoperative embolization followed by surgical excision of an intrapericardial
      pheochromocytoma.
AB  - A teenager with palpitations and hypertension was found to have an
      intrapericardial pheochromocytoma of the left atrium with multiple feeding
      collaterals. Radiologic embolization was carried out on the major feeding
      arteries to the tumor preoperatively with good angiographic result. Surgery was
      carried out the following day through a median sternotomy approach and
      cardiopulmonary bypass. Minimal bleeding was observed due to prior embolization.
      The patient made a rapid postoperative recovery and was discharged 7 days later.

PMID- 17184690
TI  - Ebstein's anomaly of the tricuspid valve in combination of tetralogy of Fallot:
      total correction in infancy.
AB  - Ebstein's anomaly of the tricuspid valve in combination with Tetralogy of Fallot
      is extremely rare. We report a patient with these combined entities in a baby
      presented with cyanosis and right heart failure soon after birth. Total
      correction toward biventricular repair was successfully conducted when he was 7
      months old. For management of a patient with such rare complex anomalies, we
      recommend Carpentier's technique for Ebstein's anomaly to restore the morphology
      of the right ventricle, and "one and half ventricle repair" can be a salvage
      procedure if the right ventricle is not functionally tolerant.

PMID- 17184672
TI  - Lung volume reduction surgery in patients with emphysema and alpha-1 antitrypsin
      deficiency.
AB  - BACKGROUND: The role of lung volume reduction surgery (LVRS) for individuals with
      alpha-1 antitrypsin (AAT) deficiency is unclear. METHODS: To assess the role of
      LVRS in individuals with severe deficiency of AAT, outcomes within the National
      Emphysema Treatment Trial were analyzed. RESULTS: Of 1218 randomized subjects, 16
      (1.3%) had severe AAT deficiency (serum level < 80 mg/dL) and a consistent
      phenotype (when available). Characteristics of these 16 patients include 87.5%
      male; median serum AAT level, 55.5 mg/dL; age, 66 years; forced expiratory volume
      in 1 second (FEV1), 27% predicted; and 50% had upper-lobe-predominant emphysema.
      All 10 subjects randomized to LVRS underwent the procedure. Although the small
      number of subjects hampered statistical analysis, 2-year mortality was higher
      with surgery (20% versus 0%) than with medical treatment. Comparison of outcomes
      between the 10 AAT-deficient and the 554 AAT-replete subjects undergoing LVRS
      showed a greater increase in exercise capacity at 6 months in replete subjects
      and a trend toward lower and shorter duration FEV1 rise in deficient individuals.
      CONCLUSIONS: This study extends to 49 cases the published experience of LVRS in
      severe AAT deficiency. Although the small number of subjects precludes firm
      conclusions, trends of lower magnitude and duration of FEV1 rise after surgery in
      AAT-deficient versus AAT-replete subjects and higher mortality in deficient
      individuals randomized to surgery versus medical treatment suggest caution in
      recommending LVRS in AAT deficiency.

PMID- 17184691
TI  - Bridge to transplantation with a left ventricular assist device for systemic
      ventricular failure after Mustard procedure.
AB  - After Mustard or Senning procedures, transplantation remains the only option for
      some patients who present at late stage with severe systemic (right) ventricular
      failure. In some circumstances these patients may require urgent mechanical
      circulatory support to bridge them to transplantation. The use of mechanical
      support poses considerable potential and actual specific problems both in terms
      of insertion and management of the device. We report the case of a 17-year-old
      patient who had a left ventricular assist device implanted from the right
      ventricle to the aorta for "end-stage" heart failure 15 years after the Mustard
      procedure. The specific problems are discussed and a management scheme is
      proposed.

PMID- 17184692
TI  - Lung large cell carcinoma producing granulocyte-colony-stimulating factor.
AB  - In recent years, tumors producing granulocyte-colony-stimulating factor have been
      reported in an increasing number of patients, the majority of which have lung
      cancer. We experience a case of lung carcinoma producing granulocyte-colony
      stimulating factor treated by resection and chemotherapy. He remains well 2 years
      and 10 months after surgery, with no recurrence of the carcinoma.

PMID- 17184693
TI  - Large clear cell tumor of the lung mimicking malignant behavior.
AB  - An 18-year-old man presented with a large (12 x 10 cm) cystic mass involving the
      lower lobe and lingula of the left lung on computed tomography. Intraoperatively
      a large cystic mass was seen densely adherent to the left lung and the chest
      wall. A left pneumonectomy was performed because of the dense adhesions and
      extreme vascularity. Pathologic examination revealed a benign sugar cell tumor of
      the lung. We believe this is the first case report of such a large, clear cell
      tumor of the lung, mimicking malignant behavior in terms of vascularity and local
      invasion and requiring pneumonectomy.

PMID- 17184694
TI  - 11C-acetate and 18F-fluorodeoxyglucose positron emission tomography of pulmonary
      adenocarcinoma.
AB  - Positron emission tomography (PET) with 11C-acetate has been recently reported in
      detection of slow-growing tumors, such as well-differentiated adenocarcinomas of
      the lung, which are often negative with 18F-fluorodeoxyglucose (FDG) PET. Here we
      present findings of acetate-PET and FDG-PET in a case of adenocarcinoma that was
      comprised of peripheral ground glass opacity and solid central components, and
      was histologically comprised of both a well-differentiated and a moderately
      differentiated adenocarcinoma, respectively. Acetate-PET was positive in both
      components, whereas FDG-PET was only positive in the solid central component. The
      present case demonstrates the figurative findings of acetate-PET and FDG-PET in
      lung adenocarcinoma.

PMID- 17184695
TI  - Prolonged survival due to spontaneous regression and surgical excision of
      malignant mesothelioma.
AB  - We report a case of malignant pleural mesothelioma with histologically proven
      spontaneous regression of pleural disease. During a 12-year follow-up there was a
      single recurrence, which was a lesion in the chest wall at 6 years that was
      surgically excised. A prominent host response to tumor was seen in both the
      primary tumor and the recurrence.

PMID- 17184696
TI  - Ectopic pleural thymoma presenting as a giant mass in the thoracic cavity.
AB  - We describe a rare case of a giant thymoma that developed in the right thoracic
      cavity, and seemed to originate from the visceral pleura. We believe that there
      have been few reports of thymoma developing from such an unusual origin.

PMID- 17184697
TI  - Minimally invasive management of Boerhaave's syndrome.
AB  - We report the case of a 42-year-old man with Boerhaave's syndrome. His medical
      history was significant only for a long-standing history of dysphagia. The
      patient presented to the emergency department with vomiting, followed by severe
      retrosternal and epigastric pain of sudden onset. An esophagogram showed evidence
      of free extravasation of contrast from the left posterolateral aspect of the
      distal esophagus just above the level of the hiatus. A minimally invasive
      technique was used to repair this injury.

PMID- 17184698
TI  - Troubleshooting for a stuck balloon-catheter.

PMID- 17184699
TI  - Tension pneumopericardium caused by pericarditis.

PMID- 17184700
TI  - The "hybrid flip-over" technique for anterior leaflet prolapse repair.
AB  - Repair of the anterior mitral leaflet or bi-leaflet prolapse is technically more
      demanding than repair of the posterior mitral leaflet. Although several
      techniques have been proposed for the repair of anterior mitral leaflet prolapse
      during bi-leaflet repair, practical challenges remain, including the
      determination of the appropriate length for artificial chords. Herein we describe
      a novel and reproducible technique for bi-leaflet mitral valve repair, including
      those with extensive anterior mitral leaflet prolapse.

PMID- 17184701
TI  - The mitral hooks: visualization of mitral valve made easy.
AB  - Historically the mitral valve has been exposed through a variety of approaches
      from the standard left atriotomy to cardiac autotransplantation. Regardless of
      the approach, adequate exposure to the mitral valve is crucial to a successful
      valve repair or replacement. We describe a simple and effective way of bringing
      the mitral valve into view through a standard left atriotomy with the use of
      specially designed and modified mitral hooks. The mitral hooks provide excellent
      unobstructed view of the mitral valve, which is suitable for repair and
      replacement.

PMID- 17184702
TI  - Tube-graft inversion for the construction of an "open" distal anastomosis during
      ascending aortic replacement: a new technique.
AB  - For the construction of a distal "open" anastomosis during ascending aortic
      replacement, a tube-graft is placed opposite to the transected aorta. We describe
      an alternative technique. The tube-graft is inverted and positioned within the
      aortic arch in a way that brings the entire circumference of the distal end of
      the tube-graft next to the circumference of the transected aorta. An end-to-end
      anastomosis is then fashioned with a running suture, the needle of which goes
      through the aorta and the tube-graft in a single pass. This technique permits
      easy, accurate, and fast suture placement, producing a hemostatic distal
      anastomosis within a short circulatory arrest time.

PMID- 17184703
TI  - Cardiac luxation to facilitate off-pump bilateral lung transplantation.
AB  - To facilitate access to the left hilum during off-pump bilateral lung
      transplantation we used the Xpose 4 apical suction device (Guidant Corp.,
      Indianapolis, IN), an off-pump coronary bypass device to luxate the heart out of
      the pericardium. The effects on circulation and possible myocardial injury were
      studied in retrospect. We found the device to provide us with an elegant and
      nondamaging method to visualize the left hilum.

PMID- 17184704
TI  - Current strategies in the surgical treatment of atrial fibrillation: review of
      the literature and Onze Lieve Vrouw Clinic's strategy.
AB  - Atrial fibrillation is the most common rhythm disturbance in clinical practice.
      It is a major source of stroke and morbidity. Although the Cox maze procedure
      effectively eliminates atrial fibrillation in most patients, the procedure has
      not found widespread application. As a consequence, new operations that use
      alternative sources of energy, such as radiofrequency, microwave, cryothermy,
      laser, and ultrasound have emerged to surgically create lesion sets to treat
      atrial fibrillation. This article reviews the fundamentals and current strategies
      in the surgical treatment of atrial fibrillation.

PMID- 17184705
TI  - Multi-detector computed tomography in coronary artery bypass graft assessment: a
      meta-analysis.
AB  - Multi-detector computed tomography (MDCT) has become an alternative to coronary
      angiography in diagnosis of graft occlusion and stenosis after coronary artery
      bypass. A literature search was performed for studies comparing angiography to 8
      slice, 16-slice, and 64-slice MDCT in the assessment of coronary grafts. In
      assessing occlusion, 14 studies produced pooled sensitivity of 97.6%, specificity
      of 98.5%, diagnostic odds ratio of 934.2, area under the curve of 0.996, and Q*
      of 0.977. Ninety-six percent of all grafts were visualized for occlusion
      assessment. Beta blockers, symptomatic status, and postoperative period did not
      significantly affect diagnostic performance. Stenosis assessment produced
      sensitivity of 88.7% and specificity of 97.4%. Eighty-eight percent of patent
      grafts could be assessed for stenosis. The diagnostic accuracy of MDCT approaches
      angiography for diagnosing graft occlusion and stenosis in patients with venous
      and arterial coronary bypass grafts. Our findings show that cardiac surgeons will
      need to interpret MDCT images of both native and grafted vessels soon in
      preparation for primary or re-do coronary bypass grafting procedures.

PMID- 17184706
TI  - Critical role of physiologist John A. Johnson in the origins of Minnesota's
      billion dollar pacemaker industry.
AB  - Complete heart block developed in more than 10% of C. Walton Lillehei's early
      patients undergoing closure of ventricular septal defects, and hospital mortality
      was 100% in this group of patients. This problem of early fatality from heart
      block was completely eliminated with the use of a myocardial electrode in
      combination with an external plug-in electric stimulator. This method of
      treatment, suggested by Dr John A. Johnson, a professor of physiology at the
      University of Minnesota, was first used by Dr Lillehei on January 30, 1957. The
      next 3 years would witness the development of a portable, external, battery
      powered pacemaker, and then an implantable pacemaker available for thousands of
      patients susceptible to lethal Stokes-Adams attacks. Fifty years have passed, and
      in 2005, approximately 800,000 pacemakers were implanted worldwide.

PMID- 17184707
TI  - Are we using the right fluid mechanics principles?

PMID- 17184710
TI  - Caution with the use of recombinant activated factor VII in treating
      postoperative hemorrhage in cardiac surgery.

PMID- 17184711
TI  - Coronary reimplantation during Jatene procedure.

PMID- 17184713
TI  - Has smoking status only a prognostic value in patients with stage I pulmonary
      adenocarcinomas?

PMID- 17184714
TI  - One-year follow-up after thoracoscopic sympathectomy for hyperhidrosis.

PMID- 17184715
TI  - "Downhill" varices--banding proximal to varix?

PMID- 17184716
TI  - Lacrimal gland extranodal marginal zone B-cell lymphoma of MALT-type.
AB  - PURPOSE: To evaluate the clinical features and outcome of extranodal marginal
      zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) in
      the lacrimal gland. DESIGN: Retrospective, noncomparative, observational case
      series in an academic referral setting. METHODS: A consecutive series of 13
      histologically verified MALT lymphoma in the lacrimal gland at presentation was
      studied. Clinical characteristics, treatment, and prognosis were analyzed.
      RESULTS: Eight males and five females with a median age of 64 years and a median
      follow-up time of 48 months were included. All patients had no prior lymphoma and
      initially presented as MALT lymphoma in the lacrimal gland. Extraorbital
      involvement at diagnosis was noted in six patients (46.2%). Two patients had
      autoimmune disease, and both had Stage IV disease at presentation. Treatment
      consisted of surgical resection in one patient, radiotherapy in four,
      chemotherapy in four, and combined radiotherapy and chemotherapy in four.
      Complete remissions were obtained in eight patients (61.5%). Patients with
      bilateral disease (61.5%) had a higher rate of advanced-stage disease and a poor
      outcome. Recurrence was noted in two patients. At the last follow-up, eight
      patients were free of disease, three were alive with disease, one died of sepsis
      as a complication of chemotherapy, and one died of lymphoma. CONCLUSIONS: MALT
      lymphoma in the lacrimal gland has a high rate of extraorbital involvement and
      synchronous bilateral lacrimal gland involvement at presentation. The prognosis
      is relatively poor, especially in patients with advanced disease and bilateral
      involvement. Extensive staging and long-term follow-up are warranted for these
      patients.

PMID- 17184717
TI  - Long-term follow-up of Intacs in keratoconus.
AB  - PURPOSE: To evaluate long-term follow-up of Intacs microthin prescription inserts
      (Addition Technology, Inc, Fremont, California, USA) for the management of
      keratoconus. DESIGN: A long-term (five years) retrospective, follow-up study.
      METHODS: Seventeen eyes of 15 patients with keratoconus ages 24 to 52 years (mean
      age +/- standard deviation [SD], 34.0 +/- 10.5 years) who had completed five
      years of follow-up (mean follow-up +/- SD, 67.2 +/- 7.5 months; range, 58 to 78
      months) were included. Two Intacs segments of 0.45-mm thickness were inserted in
      the cornea of each eye, aiming at embracing the keratoconus area to try to
      achieve maximal flattening. RESULTS: No late postoperative complications occurred
      in this series of patients. At five years, the spherical equivalent error was
      statistically significantly reduced (pre-Intacs, mean +/- SD -5.54 +/- 5.02
      diopters [D]; range, -12.50 to 3.63 D; -3.02 +/- 2.65 D; range, -8.25 to 1.88 D)
      (P = .01). Pre-Intacs uncorrected visual acuity (UCVA) was 20/50 or worse in all
      eyes (range, counting fingers to 20/50), whereas, at the last follow-up
      examination, 10 (59%) of 17 eyes had UCVA of 20/50 or better (range, counting
      fingers to 20/32). Six eyes (35%) maintained the pre-Intacs best spectacle
      corrected visual acuity (BSCVA) and one eye lost 3 lines of BSCVA, whereas the
      rest of the 10 eyes (59%) experienced a gain of one up to 8 lines. CONCLUSIONS:
      After five years, intracorneal ring segments implantation improved UCVA, BSCVA,
      and refraction in the majority of the keratoconus patients. There was no evidence
      of progressive sight-threatening complications in this study.

PMID- 17184718
TI  - Treatment of rhegmatogenous retinal detachment in teenagers by pneumatic
      retinopexy technique.
AB  - PURPOSE: To evaluate the effectiveness of pneumatic retinopexy as an alternative
      technique for rhegmatogenous retinal detachment (RD) repair in teenagers. DESIGN:
      Retrospective, noncomparative, interventional case series. METHODS: We conducted
      a review of 19 patients (19 eyes) younger than 20 years of age who had undergone
      pneumatic retinopexy as the initial procedure for rhegmatogenous RD between 1995
      and 2002. RESULTS: Fourteen boys and five girls (mean age of 17.1 years) were
      included in this study. Two eyes had a history of trauma. Seventeen eyes (89.5%)
      had myopia of > -3 diopters. The averaged refraction of the operated eyes was 
      6.11 diopters (range, -1.25 to -9.5 diopters). Macular detachment was found in 13
      eyes (68.4%). Subretinal fibrosis was present in six eyes (31.6%). Pneumatic
      retinopexy resulted in reattachment in 16 eyes (84.2%) with one injection of gas.
      One patient required a second injection of gas. Two patients needed additional
      scleral buckling to attach the retina. Displaced subretinal fluid and delayed
      resorption of subretinal fluid were noted in four eyes. Mean follow-up period was
      42.7 months (range, six to 75 months). CONCLUSIONS: Rhegmatogenous RD in
      teenagers can be treated with pneumatic retinopexy with an overall successful
      rate as in adults. More attention is required regarding the postoperative stage
      and follow-up period to ensure surgical success.

PMID- 17184719
TI  - Discordance between subjective perimetric visual fields and objective multifocal
      visual evoked potential-determined visual fields in patients with hemianopsia.
AB  - PURPOSE: To investigate the concordance between subjectively and objectively
      acquired visual fields in patients with subjectively determined hemianopsia.
      DESIGN: Retrospective observational study. METHODS: Ten patients, six men and
      four women, ranging in age from 28 to 68 years, were studied. Goldmann or
      Humphrey perimeters were used to obtain the subjectively determined visual fields
      for up to 25 degrees of eccentricity, and the VERIS Scientific System (Electro
      Diagnostic Imaging, San Francisco, California, USA) was used to record multifocal
      visual evoked potential [VEPs] (mfVEPs) to obtain the objective visual fields.
      Each of the 60 black-and-white segments of the checkerboard stimulus was
      alternated according to a binary m sequence. The first slices of the second-order
      kernels were extracted and analyzed. RESULTS: In five cases, the visual field
      loci where the mfVEPs were within normal limits corresponded to the scotomatous
      areas obtained by conventional perimetry. In these discordant cases, the lesions
      (e.g., arteriovenous malformation) were located in the occipital lobe. Two of
      these cases had a complete recovery of the subjective visual field. The lesions
      of the concordant cases were located outside the occipital lobe (e.g., pituitary
      adenoma). In these cases, no visual field improvement was seen. The temporal
      crescent syndrome was ruled out in patients with posterior lesions by computed
      tomography (CT) or magnetic resonance imaging (MRI) findings. CONCLUSIONS: In
      some patients with occipital lesions, the subjective and objective visual field
      results are discordant, and some of them will show a recovery of the visual field
      deficits.

PMID- 17184720
TI  - Artificial neural networks for qualitative and quantitative analysis of target
      proteins with polymerized liposome vesicles.
AB  - We investigate the feasibility of using the luminescence response of polymerized
      liposomes incorporating ethylenediaminetetraacetate europium(III) (EDTA-Eu(3+))
      for monitoring protein concentrations in aqueous media. Quantitative analysis is
      based on the linear relationship between the luminescence enhancement of the
      lanthanide ion and protein concentration. Analytical figures of merit are
      presented for carbonic anhydrase, human serum albumin, gamma-globulins, and
      thermolysin. Qualitative analysis is based on the luminescence lifetime of the
      liposome sensor. This parameter, which follows well-behaved single exponential
      decays and provides characteristic values for each of the four studied proteins,
      demonstrates the selective potential for protein identification. Then partial
      least squares-1 and artificial neural networks are compared toward the
      quantitative and qualitative analysis of human serum albumin and carbonic
      anhydrase in binary mixtures without previous separation at the concentration
      levels found in aqueous humor.

PMID- 17184721
TI  - Label-free detection of biomolecules on microarrays using surface-colloid
      interaction.
AB  - Binding of charged nanoparticles to nonmodified DNA and RNA target molecules on
      microarrays allows detection of these nucleic acids by locating bound
      nanoparticles on microarray surface. Two computational models have been developed
      to study the ionic interaction of colloidal particles and biopolymer molecules on
      a microarray surface. One model represents a basic approach based on mass action
      law for simulation charge effects versus the chemical composition of the
      interacting array surface and nanoparticle. The second model is implementation of
      the advanced Gouy-Chapman-Stern-Graham model for describing effects on liquid
      solid interface. We found that both models predict selective binding of colloidal
      particles to large target molecules on the surface with no binding to smaller
      capture molecules. This binding regime is considered to be very beneficial for
      application of charged nanoparticles for detection of nonmodified DNA and RNA
      target molecules on microarrays. The theoretical considerations are in
      qualitative agreement with the experimental results for detecting large target
      DNA and a 50-base long synthetic oligonucleotide on the amino-modified microarray
      substrate. The experimental and theoretical results of this study allow further
      development of the label-free microarray technology demonstrated previously for
      gene expression analysis that is free of reverse transcription and dye labeling.

PMID- 17184722
TI  - Targeting linear duplex DNA with mixed-base peptide nucleic acid oligomers
      facilitated by bisPNA openers.

PMID- 17184723
TI  - Quenching-enhanced fluorescence titration protocol for accurate determination of
      free energy of membrane binding.

PMID- 17184724
TI  - Substrate specificity of recombinant dengue 2 virus NS2B-NS3 protease: influence
      of natural and unnatural basic amino acids on hydrolysis of synthetic fluorescent
      substrates.
AB  - A recombinant dengue 2 virus NS2B-NS3 protease (NS means non-structural virus
      protein) was compared with human furin for the capacity to process short peptide
      substrates corresponding to seven native substrate cleavage sites in the dengue
      viral polyprotein. Using fluorescence resonance energy transfer peptides to
      measure kinetics, the processing of these substrates was found to be selective
      for the Dengue protease. Substrates containing two or three basic amino acids
      (Arg or Lys) in tandem were found to be the best, with Abz-AKRRSQ-EDDnp being the
      most efficiently cleaved. The hydrolysis of dipeptide substrates Bz-X-Arg-MCA
      where X is a non-natural basic amino acid were also kinetically examined, the
      best substrates containing aliphatic basic amino acids. Our results indicated
      that proteolytic processing by dengue NS3 protease, tethered to its activating
      NS2B co-factor, was strongly inhibited by Ca2+ and kosmotropic salts of the
      Hofmeister's series, and significantly influenced by substrate modifications
      between S4 and S6'. Incorporation of basic non-natural amino acids in short
      peptide substrates had significant but differential effects on Km and k(cat),
      suggesting that further dissection of their influences on substrate affinity
      might enable the development of effective dengue protease inhibitors.

PMID- 17184725
TI  - Formamide probes a role for water in the catalytic cycle of cytochrome c oxidase.
AB  - Formamide is a slow-onset inhibitor of mitochondrial cytochrome c oxidase that is
      proposed to act by blocking water movement through the protein. In the presence
      of formamide the redox level of mitochondrial cytochrome c oxidase evolves over
      the steady state as the apparent electron transfer rate from cytochrome a to
      cytochrome a(3) slows. At maximal inhibition cytochrome a and cytochrome c are
      fully reduced, whereas cytochrome a(3) and Cu(B) remain fully oxidized consistent
      with the idea that formamide interferes with electron transfer between cytochrome
      a and the oxygen reaction site. However, transient kinetic studies show that
      intrinsic rates of electron transfer are unchanged in the formamide-inhibited
      enzyme. Formamide inhibition is demonstrated for another member of the heme
      oxidase family, cytochrome c oxidase from Bacillus subtilis, but the onset of
      inhibition is much quicker than for mitochondrial oxidase. If formamide
      inhibition arises from a steric blockade of water exchange during catalysis then
      water exchange in the smaller bacterial oxidase is more open. Subunit III removal
      from the mitochondrial oxidase hastens the onset of formamide inhibition
      suggesting a role for subunit III in controlling water exchange during the
      cytochrome c oxidase reaction.

PMID- 17184726
TI  - Drastic changes in the ligand structure of the oxygen-evolving Mn cluster upon
      Ca2+ depletion as revealed by FTIR difference spectroscopy.
AB  - A Fourier transform infrared (FTIR) difference spectrum of the oxygen-evolving Mn
      cluster upon the S(1)-to-S(2) transition was obtained with Ca(2+)-depleted
      photosystem II (PSII) membranes to investigate the structural relevance of Ca(2+)
      to the Mn cluster. Previously, Noguchi et al. [Biochim. Biophys. Acta 1228 (1995)
      189] observed drastic changes in the carboxylate stretching region of the
      S(2)/S(1) FTIR spectrum upon Ca(2+) depletion, whereas Kimura and co-workers
      [Biochemistry 40 (2001) 14061; ibid. 41 (2002) 5844] later claimed that these
      changes were not ascribed to Ca(2+) depletion itself but caused by the
      interaction of EDTA to the Mn cluster and/or binding of K(+) at the Ca(2+) site.
      In the present study, the preparation of the Ca(2+)-depleted PSII sample and its
      FTIR measurement were performed in the absence of EDTA and K(+). The obtained
      S(2)/S(1) spectrum exhibited the loss of carboxylate bands at 1587/1562 and
      1364/1403 cm(-1) and diminished amide I intensities, which were identical to the
      previous observations in the presence of EDTA and K(+). This result indicates
      that the drastic FTIR changes are a pure effect of Ca(2+) depletion, and provides
      solid evidence for the general view that Ca(2+) is strongly coupled with the Mn
      cluster.

PMID- 17184727
TI  - Bio-photosensor: Cyanobacterial photosystem I coupled with transistor via
      molecular wire.
AB  - We report on the first successful output of electrons directly from photosystem I
      (PSI) of thermophilic cyanobacteria to the gate of a field-effect transistor
      (FET) by bypassing electron flow via a newly designed molecular wire, i.e.,
      artificial vitamin K(1), and a gold nanoparticle; in short, this newly
      manufactured photosensor employs a bio-functional unit as the core of the device.
      Photo-electrons generated by the irradiation of molecular complexes composed of
      reconstituted PSI on the gate were found to control the FET. This PSI-bio
      photosensor can be used to interpret gradation in images. This PSI-FET system is
      moreover sufficiently stable for use exceeding a period of 1 year.

PMID- 17184728
TI  - Environmentally modulated phosphorylation and dynamics of proteins in
      photosynthetic membranes.
AB  - Recent advances in vectorial proteomics of protein domains exposed to the surface
      of photosynthetic thylakoid membranes of plants and the green alga Chlamydomonas
      reinhardtii allowed mapping of in vivo phosphorylation sites in integral and
      peripheral membrane proteins. In plants, significant changes of thylakoid protein
      phosphorylation are observed in response to stress, particularly in photosystem
      II under high light or high temperature stress. Thylakoid protein phosphorylation
      in the algae is much more responsive to the ambient redox and light conditions,
      as well as to CO(2) availability. The light-dependent multiple and differential
      phosphorylation of CP29 linker protein in the green algae is suggested to control
      photosynthetic state transitions and uncoupling of light harvesting proteins from
      photosystem II under high light. The similar role for regulation of the dynamic
      distribution of light harvesting proteins in plants is proposed for the TSP9
      protein, which together with other recently discovered peripheral proteins
      undergoes specific environment- and redox-dependent phosphorylation at the
      thylakoid surface. This review focuses on the environmentally modulated
      reversible phosphorylation of thylakoid proteins related to their membrane
      dynamics and affinity towards particular photosynthetic protein complexes.

PMID- 17184729
TI  - In the early phase of programmed cell death in Tobacco Bright Yellow 2 cells the
      mitochondrial adenine nucleotide translocator, adenylate kinase and nucleoside
      diphosphate kinase are impaired in a reactive oxygen species-dependent manner.
AB  - To investigate whether and how mitochondria can change in plant programmed cell
      death (PCD), we used the non-photosynthetic Tobacco Bright Yellow 2 (TBY-2)
      cells. These can be synchronized to high levels, stand out in terms of growth
      rate and homogeneity and undergo PCD as a result of heat shock. Using these cells
      we investigated the activity of certain mitochondrial proteins that have a role
      in providing ATP and/or other nucleoside triphosphates (NTPs). We show that,
      already after 2 h from the heat shock, when cell viability remains unaffected,
      the rate of ADP/ATP exchange due to adenine nucleotide translocator (ANT)
      activity, and the rate of the reactions catalysed by adenylate kinase (ADK; EC
      2.7.4.3) and nucleoside diphosphate kinase (NDPK; EC 2.7.4.6) are inhibited in a
      non-competitive-like manner. In all cases, externally added ascorbate partially
      prevented the inhibition. These effects occurred in spite of minor (for ANT) or
      no changes in the mitochondrial protein levels as immunologically investigated.
      Interestingly, a decrease of both the steady state level of the ascorbate pool
      and of the activity of l-galactono-gamma-lactone dehydrogenase (GLDH) (EC
      1.3.2.3), the mitochondrial enzyme catalysing the last step of ascorbate
      biosynthesis, were also found.

PMID- 17184730
TI  - On the enigma of pain and hyperalgesia: A molecular perspective.
AB  - Pain is a common symptom of injuries and inflammatory-related conditions. The
      perception of pain, commonly known as nociception, depends on integrated
      receptors and molecular pathways. Inflammatory mediators are involved in the
      genesis, persistence, and severity of pain. Noxious stimuli can trigger a cascade
      of inflammatory loops that feedback onto sensory modalities and domains of the
      CNS, in an attempt to alert the brain of deregulated homeostasis. Understanding
      the mechanisms of pain continue to make nociception and hyperalgesia a burgeoning
      field of research.

PMID- 17184731
TI  - Ghrelin stimulates angiogenesis in human microvascular endothelial cells:
      Implications beyond GH release.
AB  - Ghrelin, a peptide hormone isolated from the stomach, releases growth hormone and
      stimulates appetite. Ghrelin is also expressed in pancreas, kidneys,
      cardiovascular system and in endothelial cells. The precise role of ghrelin in
      endothelial cell functions remains unknown. We examined the expression of ghrelin
      and its receptor (GHSR1) mRNAs and proteins in human microvascular endothelial
      cells (HMVEC) and determined whether ghrelin affects in these cells
      proliferation, migration and in vitro angiogenesis; and whether MAPK/ERK2
      signaling is important for the latter action. We found that ghrelin and GHSR1 are
      constitutively expressed in HMVEC. Treatment of HMVEC with exogenous ghrelin
      significantly increased in these cells proliferation, migration, in vitro
      angiogenesis and ERK2 phosphorylation. MEK/ERK2 inhibitor, PD 98059 abolished
      ghrelin-induced in vitro angiogenesis. This is the first demonstration that
      ghrelin and its receptor are expressed in human microvascular endothelial cells
      and that ghrelin stimulates HMVEC proliferation, migration, and angiogenesis
      through activation of ERK2 signaling.

PMID- 17184732
TI  - Sphingosine 1-phosphate receptors modulate intracellular Ca2+ homeostasis.
AB  - Ligation of sphingosine 1-phosphate (S1P) to a set of specific receptors named
      S1P receptors (S1PRs) regulates important biological processes. Although the
      ability of S1P to increase cytosolic Ca2+ in various cell types is well known,
      the role of the individual S1PRs has not been fully characterized. Here, we
      provide a complete analysis of S1P-dependent intracellular Ca2+ homeostasis in
      HeLa cells. Overexpression of S1P2, or S1P3, but not S1P1, leads to a significant
      increase in cytosolic and mitochondrial [Ca2+] in response to S1P challenge.
      Moreover, cells ectopically expressing S1P2, or S1P3 exhibited an appreciable
      decrease of the free Ca2+ concentration in the endoplasmic reticulum, dependent
      on stimulation of receptors by S1P endogenously present in the culture medium
      which was accompanied by a reduced susceptibility to C2-ceramide-induced cell
      death. These results demonstrate a differential contribution of individual S1PRs
      to Ca2+ homeostasis and its possible implication in the regulation of cell
      survival.

PMID- 17184733
TI  - Characterizations of distinct amyloidogenic conformations of the Abeta (1-40) and
      (1-42) peptides.
AB  - Major constituents of the amyloid plaques found in the brain of Alzheimer's
      patients are the 39-43 residue beta-amyloid (Abeta) peptides. Extensive in vitro
      as well as in vivo biochemical studies have shown that the 40- and 42-residue
      Abeta peptides play major roles in the neurodegenerative pathology of Alzheimer's
      disease. Although the two Abeta peptides share common aggregation properties, the
      42-residue peptide is more amyloidogenic and more strongly associated with
      amyloid pathology. Thus, characterizations of the two Abeta peptides are of
      critical importance in understanding the molecular mechanism of Abeta amyloid
      formation. In this report, we present combined CD and NMR studies of the
      monomeric states of the two peptides under both non-amyloidogenic (<5 degrees C)
      and amyloid-forming conditions (>5 degrees C) at physiological pH. Our CD studies
      of the Abeta peptides showed that initially unfolded Abeta peptides at low
      temperature (<5 degrees C) gradually underwent conformational changes to more
      beta-sheet-like monomeric intermediate states at stronger amyloidogenic
      conditions (higher temperatures). Detailed residue-specific information on the
      structural transition was obtained by using NMR spectroscopy. Residues in the N
      terminal (3-12) and 20-22 regions underwent conformational changes to more
      extended structures at the stronger amyloidogenic conditions. Almost identical
      structural transitions of those residues were observed in the two Abeta peptides,
      suggesting a similar amyloidogenic intermediate for the two peptides. The 42
      residue Abeta (1-42) peptide was, however, more significantly structured at the C
      terminal region (39-42), which may lead to the different aggregation propensity
      of the two peptides.

PMID- 17184734
TI  - Embellistatin, a microtubule polymerization inhibitor, inhibits angiogenesis both
      in vitro and in vivo.
AB  - The efficient inhibition of angiogenesis is considered as a promising strategy
      for the treatment of angiogenesis-related diseases including cancer. Herein, we
      report that embellistatin, a bicyclic ketone compound known as a microtubule
      polymerization inhibitor, exhibits anti-angiogenic activity. Embellistatin
      inhibited in vitro angiogenesis of bovine aortic endothelial cells (BAECs) such
      as bFGF-induced invasion and tube formation as well as bFGF-induced mouse corneal
      angiogenesis in vivo. Notably, embellistatin exhibited stronger inhibition
      activity for the growth of BAECs than that of normal and cancer cell lines. Cell
      cycle analysis revealed that the compound arrests cell cycle at G2/M phase, which
      is associated with the increased expression of p21(WAF1) and p53 partly. These
      results demonstrate that embellistatin may serve the basis for the development of
      new anti-angiogenic agents.

PMID- 17184735
TI  - A putative transcriptional elongation factor hIws1 is essential for mammalian
      cell proliferation.
AB  - Iws1 has been implicated in transcriptional elongation by interaction with RNA
      polymerase II (RNAP II) and elongation factor Spt6 in budding yeast Saccharomyces
      cerevisiae, and association with transcription factor TFIIS in mammalian cells,
      but its role in controlling cell growth and proliferation remains unknown. Here
      we report that the human homolog of Iws1, hIws1, physically interacts with
      protein arginine methyltransferases PRMT5 which methylates elongation factor Spt5
      and regulates its interaction with RNA polymerase II. Gene-specific silencing of
      hIws1 by RNA interference reveals that hIws1 is essential for cell viability. GFP
      fusion protein expression approaches demonstrate that the hIws1 protein is
      located in the nucleus, subsequently, two regions harbored within the hIws1
      protein are demonstrated to contain nuclear localization signals (NLSs). In
      addition, mouse homolog of hiws1 is found to express ubiquitously in various
      tissues.

PMID- 17184736
TI  - Targeting of nanoparticles to the clathrin-mediated endocytic pathway.
AB  - Nanoparticles (NPs) are considered attractive carriers for gene therapy and drug
      delivery owing to their minor toxic effect and their ability to associate and
      internalize into mammalian cells. In this study, we compared the endocytosis into
      HeLa cells of NPs exposing either a negative or positive charge on their surface.
      The exposed charge significantly affected their ability to internalize as well as
      the cellular endocytosis mechanism utilized. Negatively charged NPs show an
      inferior rate of endocytosis and do not utilize the clathrin-mediated endocytosis
      pathway. On the other hand, positively charged NPs internalize rapidly via the
      clathrin-mediated pathway. When this pathway is blocked, NPs activate a
      compensatory endocytosis pathway that results in even higher accumulation of NPs.
      Overall, the addition of a positive charge to NPs may improve their potential as
      nanoparticulate carriers for drug delivery.

PMID- 17184737
TI  - The Burkholderia cepacia bceA gene encodes a protein with phosphomannose
      isomerase and GDP-D-mannose pyrophosphorylase activities.
AB  - The bceA gene is part of the Burkholderia cepacia IST408 exopolysaccharide (EPS)
      biosynthetic cluster. It encodes a 55.3-kDa bifunctional protein (type II PMI
      family) with phosphomannose isomerase (PMI) and GDP-mannose pyrophosphorylase
      (GMP) activities. GMP activity is strongly dependent on the presence of Ca(2+) or
      Mn(2+), while PMI activity can use a broader variety of divalent cations
      (Ca(2+)>Mn(2+)>Mg(2+)>Co(2+)>Ni(2+)). The lack of a functional bceA gene does not
      affect EPS production yield in a non-polar insertion bceA mutant. The in silico
      search for putative bceA homologues revealed the presence of 2-5 bceA orthologues
      in the Burkholderia genomes available. This suggests that in B. cepacia IST408
      putative bceA functional homologues may compensate the bceA mutation. However,
      the viscosity of aqueous solutions prepared with the EPS produced by the bceA
      mutant was significantly reduced compared with wild-type biopolymer and the
      mutant forms biofilms with a size reduced by 6-fold.

PMID- 17184738
TI  - Functional CRF receptors in BON cells stimulate serotonin release.
AB  - BON cells are human, pancreatic carcinoid-derived, endocrine-like cells that
      share functional similarities with intestinal enterochromaffin (EC) cells. We
      investigated the presence of corticotropin-releasing factor (CRF) receptors,
      their signalling pathways and the functional effects of their stimulation in BON
      cells (clone #7). Expression analysis showed that BON cells contain mRNA for the
      CRF receptor types 1 and 2 (CRF1/2), although CRF2 mRNA levels were 23-fold
      higher than those of CRF1 mRNA. The CRF1/2 ligand, rat/human (r/h)CRF (EC50 = 233
      nM), and the selective CRF2 ligand, human urocortin 3 (Ucn 3) (EC50 = 48 nM),
      induced a dose-dependent increase in cAMP formation. Effects of r/hCRF were
      blocked by 44% with the selective CRF1 antagonist DMP-696, while the selective
      CRF2 antagonist antisauvagine-30 had only marginal effects. Both ligands (100 nM)
      stimulated the release of serotonin with similar efficacy (3-fold increase over
      basal). Effects of r/hCRF, but not Ucn 3, were blocked by pre-incubation with
      antisauvagine-30. These observations demonstrate that the EC cell-related BON
      cells express functional CRF2 receptors linked to the release of serotonin. This
      suggests that EC cells may be a target for CRF and/or Ucn 3 in the intestine
      during stress-related responses. Actions of CRF/Ucn 3 and EC cell-derived
      mediators, such as serotonin, might underlie several motor, secretory and/or
      sensory disorders of the gastrointestinal (GI) tract which may play a role in the
      pathophysiology of functional GI disorders, such as irritable bowel syndrome.

PMID- 17184740
TI  - Autocorrelogram sorting: a novel method for evaluating negative-feedback
      regulation of spike firing.
AB  - Spontaneously firing units were recorded extracellularly from the hippocampus of
      anesthetized rats, and autocorrelograms were conventionally constructed. These
      conventional autocorrelograms were sorted into frequency-specific
      autocorrelograms according to the instantaneous firing frequency of the spike at
      Deltat=0, which was calculated based on the interval between the spike at
      Deltat=0 and the preceding spike. In this fashion, we found that autocorrelogram
      values were negatively correlated with instantaneous firing frequency during the
      4-12 ms post-spike time period. The negative correlation during the 4-6 ms post
      spike period could not have been due to the refractory period or GABAergic
      inhibition, and thus represented a third type of feedback regulation of spike
      firing completed within single neurons. Application of acetylcholine
      significantly enhanced this feedback regulation. Our 'autocorrelogram sorting'
      method thus proved to be successful in detecting cholinergically enhanced
      feedback regulation of spike firing intrinsic to single neurons.

PMID- 17184739
TI  - Effects of glial cell line-derived neurotrophic factor deletion on ventral
      mesencephalic organotypic tissue cultures.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is potent for survival and
      promotion of nerve fibers from midbrain dopamine neurons. It is also known to
      exert different effects on specific subpopulations of dopamine neurons. In
      organotypic tissue cultures, dopamine neurons form two diverse nerve fiber growth
      patterns, targeting the striatum differently. The aim of this study was to
      investigate the effect of GDNF on the formation of dopamine nerve fibers.
      Organotypic tissue cultures of ventral mesencephalon of gdnf gene-deleted mice
      were studied. The results revealed that dopamine neurons survive in the absence
      of GDNF. Tyrosine hydroxylase immunoreactivity demonstrated, in gdnf knockout and
      wildtype cultures, nerve fiber formation with two separate morphologies occurring
      either in the absence or the presence of astrocytes. The outgrowth that occurred
      in the absence of astrocytes was unaffected by gdnf deletion, whereas nerve
      fibers guided by the presence of astrocytes were affected in that they reached
      significantly shorter distances from the gdnf gene-deleted tissue slice, compared
      to those measured in wildtype cultures. Treatment with GDNF reversed this effect
      and increased nerve fiber density independent of genotype. Furthermore, migration
      of astrocytes reached significantly shorter distances from the tissue slice in
      GDNF knockout compared to wildtype cultures. Exogenous GDNF increased astrocytic
      migration in gdnf gene-deleted tissue cultures, comparable to lengths observed in
      wildtype tissue cultures. In conclusion, cultured midbrain dopamine neurons
      survive in the absence of GDNF, and the addition of GDNF improved dopamine nerve
      fiber formation - possibly as an indirect effect of astrocytic stimulation.

PMID- 17184742
TI  - Effect of kainic acid treatment on insulin-like growth factor-2 receptors in the
      IGF2-deficient adult mouse brain.
AB  - Insulin-like growth factor-2 (IGF2) is a member of the insulin gene family with
      known neurotrophic properties. The actions of IGF2 are mediated via the IGF type
      1 and type 2 receptors as well as through the insulin receptors, all of which are
      widely expressed throughout the brain. Since IGF2 is up-regulated in the brain
      after injury, we wanted to determine whether the absence of IGF2 can lead to any
      alteration on brain morphology and/or in the response of its receptor binding
      sites following a neurotoxic insult. No morphological differences were observed
      between the brains of IGF2 knockout (IGF2(-/-)) and wild-type control (IGF2(+/+))
      mice. However, our in vitro receptor autoradiography results indicate that IGF2(
      /-) mice had lower endogenous levels of [(125)I]IGF1 and [(125)I]insulin receptor
      binding sites in the hippocampus and cerebellum as compared to IGF2(+/+) mice,
      while endogenous [(125)I]IGF2 receptor binding showed a decrease only in the
      cerebellum. Seven days after kainic acid administration, the [(125)I]insulin
      receptor binding sites were significantly decreased in all brain regions of the
      IGF2(+/+) mice, while the levels of [(125)I]IGF1 and [(125)I]IGF2 binding sites
      were decreased only in select brain areas. The IGF2(-/-) mice, on the other hand,
      showed increased [(125)I]IGF1 and [(125)I]IGF2 and [(125)I]insulin receptor
      binding sites in selected regions such as the hippocampus and cerebellum. These
      results, taken together, suggest that deletion of IGF2 gene does not affect gross
      morphology of the brain but does selectively alter endogenous [(125)I]IGF1,
      [(125)I]IGF2 and [(125)I]insulin receptor binding sites and their response to
      neurotoxicity.

PMID- 17184744
TI  - Timing of ascending and descending visual signals predicts the response mode of
      single cells in the thalamic nucleus rotundus of the pigeon (Columba livia).
AB  - Neurons of the pigeon's diencephalic n. rotundus were demonstrated to show visual
      responses of short and long latency representing ascending signals of the retino
      tecto-rotundal system and descending signals from telencephalo-tecto-rotundal
      fibers. Pigeons thus provide an ideal model to investigate the convergence of
      ascending and descending visual processing streams at single cell level. Although
      it is known that rotundal responses of long latency show distinct response
      characteristics, dependent on the stimulus being presented monocularly or
      binocularly, the mechanisms underlying these response differences are still
      unclear. While it is possible that the simultaneity of eye stimulation produces a
      change of processing, it is also possible that the relative timing and order
      between ipsilateral and contralateral signals are the decisive variable. To test
      between both possibilities, we recorded from cells in the pigeon's n. rotundus
      while providing monocular or binocular visual stimulation and varying the delay
      and order of eye presentations. We revealed that the precise temporal interaction
      and order of ascending and descending inputs to the tectum decide about late
      responses with burst or tonic characteristics. When descending signals reached
      the tectum before the ascending signals, rotundal cells showed late responses
      that were characterized by burst activity patterns. When ascending input reached
      the tectum first, responses with tonic characteristic were observed. These
      effects might become mediated by intratectal mechanisms, the nucleus
      ventrolateralis thalami, or the bed nuclei of the tectothalamic tract and might
      constitute the neural basis of a bihemispheric gating function.

PMID- 17184741
TI  - Opposing effects of spinal nerve ligation on calcium-activated potassium currents
      in axotomized and adjacent mammalian primary afferent neurons.
AB  - Calcium-activated potassium channels regulate AHP and excitability in neurons.
      Since we have previously shown that axotomy decreases I(Ca) in DRG neurons, we
      investigated the association between I(Ca) and K((Ca)) currents in control medium
      sized (30-39 microM) neurons, as well as axotomized L5 or adjacent L4 DRG neurons
      from hyperalgesic rats following L5 SNL. Currents in response to AP waveform
      voltage commands were recorded first in Tyrode's solution and sequentially after:
      1) blocking Na(+) current with NMDG and TTX; 2) addition of K((Ca)) blockers with
      a combination of apamin 1 microM, iberiotoxin 200 nM, and clotrimazole 500 nM; 3)
      blocking remaining K(+) current with the addition of 4-AP, TEA-Cl, and
      glibenclamide; and 4) blocking I(Ca) with cadmium. In separate experiments,
      currents were evoked (HP -60 mV, 200 ms square command pulses from -100 to +50
      mV) while ensuring high levels of activation of I(K(Ca)) by clamping cytosolic
      Ca(2+) concentration with pipette solution in which Ca(2+) was buffered to 1
      microM. This revealed I(K(Ca)) with components sensitive to apamin, clotrimazole
      and iberiotoxin. SNL decreases total I(K(Ca)) in axotomized (L5) neurons, but
      increases total I(K(Ca)) in adjacent (L4) DRG neurons. All I(K(Ca)) subtypes are
      decreased by axotomy, but iberiotoxin-sensitive and clotrimazole-sensitive
      current densities are increased in adjacent L4 neurons after SNL. In an
      additional set of experiments we found that small-sized control DRG neurons also
      expressed iberiotoxin-sensitive currents, which are reduced in both axotomized
      (L5) and adjacent (L4) neurons. CONCLUSIONS: Axotomy decreases I(K(Ca)) due to a
      direct effect on K((Ca)) channels. Axotomy-induced loss of I(Ca) may further
      potentiate current reduction. This reduction in I(K(Ca)) may contribute to
      elevated excitability after axotomy. Adjacent neurons (L4 after SNL) exhibit
      increased I(K(Ca)) current.

PMID- 17184745
TI  - Distribution of neurokinin A-like and serotonin immunoreactivities within the
      vertical lobe complex in Sepia officinalis.
AB  - Immunohistochemistry, using antibodies raised against mammalian neurokinin A
      (NKA) and serotonin (5-HT), was applied in double-staining experiments to map
      these molecules within the vertical lobe complex (inferior frontal, superior
      frontal, post-frontal, vertical, subvertical and precommissural lobes). NKA-like
      and 5-HT immunoreactivities were detected in all the lobes of the vertical lobe
      complex but were never colocalized in cell bodies or fibres. Except for the cell
      layers of the superior frontal lobe, both types of labelled cell bodies were
      observed in all the lobes. Both types of immunoreactive fibres were detected in
      all the neuropils and interestingly revealed clear subdivisions within some
      lobes, e.g., 5-HT-IR fibres were more abundant in the peripheral part of the
      vertical lobe whereas NKA-IR ones were widely observed in both the peripheral and
      central parts. In cephalopods, the vertical lobe complex is involved in learning
      and memory; thus, our results strongly suggest that one or more NKA-like and 5-HT
      molecules may function as neurochemical messengers in these cognitive processes.

PMID- 17184743
TI  - Effect of synthetic matrix metalloproteinase inhibitors on lipopolysaccharide
      induced blood-brain barrier opening in rodents: Differences in response based on
      strains and solvents.
AB  - Matrix metalloproteinase inhibitors (MMPIs) reduce blood-brain barrier (BBB)
      disruption and prevent cell death. Animal models of multiple sclerosis, cerebral
      ischemia and hemorrhage, and bacterial meningitis respond to treatment with
      MMPIs. We have used the intracerebral injection of lipopolysaccharide (LPS) in
      rat, which induces MMP production and results in a delayed opening of the BBB, to
      screen MMPIs to identify therapeutic agents. We hypothesized that the mouse would
      respond similarly to LPS and that the mouse/LPS model of BBB damage would be more
      useful for screening of MMPIs. Therefore, we adapted the rat LPS model to the
      mouse and compared the response to LPS and treatment with MMPIs. Wistar-Kyoto
      rats (WKY) and three strains of mice had stereotactic injections of LPS into the
      caudate. (14)C-sucrose was used to measure permeability of the BBB 24 h after
      injection. Initially, we tested three broad-spectrum MMPIs in the rat, BB-1101,
      BB-94, and BB-2293, and a MMP-2 selective inhibitor, IW449; both BB-1101 and BB
      94 significantly suppressed LPS-induced BBB damage (p<0.05). In the 3 mouse
      strains, C57/BL6, C57/BL10, and C57/BL10HIIIR2, LPS significantly opened the BBB
      in C57/BL6, and it was the only strain that showed a reduction in BBB
      permeability with BB-94. Treatment with methylprednisolone and several broad
      spectrum MMPIs, including BB-1101, was ineffective in the C57/BL6. There was a
      significant reduction in BBB permeability seen with 10% dimethyl sulfoxide (DMSO)
      alone, which was used to dissolve the selective MMP-2 and-9 inhibitor, SB-3CT.
      The tetracycline derivative, minocycline, reduced the BBB injury in mouse by
      blocking the production of MMP-9. Our results show variability in rats and mice
      to LPS and MMPIs, which most likely is based on genetic make-up. Understanding
      these differences may provide important clues that could guide selection of MMPIs
      in treatment of neurological diseases.

PMID- 17184746
TI  - ATP- and ACh-induced responses in isolated cat petrosal ganglion neurons.
AB  - Chemoreceptor (glomus) cells of the carotid body are synaptically connected to
      the sensory nerve endings of petrosal ganglion (PG) neurons. In response to
      natural stimuli, the glomus cells release transmitters, which acting on the nerve
      terminals of petrosal neurons increases the chemosensory afferent discharge.
      Among several transmitter molecules present in glomus cells, acetylcholine (ACh)
      and adenosine 5'-triphosphate (ATP) are considered to act as excitatory
      transmitter in this synapse. To test if ACh and ATP play a role as excitatory
      transmitters in the cat CB, we recorded the electrophysiological responses from
      PG neurons cultured in vitro. Under voltage clamp, ATP induces a concentration
      dependent inward current that partially desensitizes during 20-30 s application
      pulses. The ATP-induced current has a threshold near 100 nM and saturates between
      20-50 muM. ACh induces a fast, inactivating inward current, with a threshold
      between 10-50 muM, and saturates around 1 mM. A large part of the population of
      PG neurons (60%) respond to both ATP and ACh. Present results support the
      hypothesis that ACh and ATP act as excitatory transmitters between cat glomus
      cells and PG neurons.

PMID- 17184747
TI  - Categorical perception of anger and disgust facial expression is affected by non
      clinical social anxiety: an ERP study.
AB  - Anxiety has been associated with a bias for interpreting threatening information.
      Faces expressing anger seem to be more easily detected by socially anxious
      individuals than by non-anxious individuals. Similarly, disgust on a face may
      also reflect a negative social judgment. We tested the hypothesis that
      individuals displaying non-clinical social anxiety would be as sensitive to
      disgust as to anger interpretation by comparing individuals scoring high or low
      on the fear of social evaluation scale (FNE, Watson and Friend, 1969). Event
      related potentials (ERP) were recorded in response to repetitions of a particular
      facial expression (e.g. anger) and in response to two deviating (rare) stimuli
      obtained by a morphing procedure, where one depicted the same emotion as the
      frequent stimulus, while the other depicted a different facial expression (e.g.
      disgust). The classic effect of categorical perception was reproduced: at a
      behavioral level, people detected more easily rare faces depicting a different
      emotion than faces depicting the same emotion. ERP results suggest that deviant
      faces depicting a different emotion evoked an earlier attentional N2b/P3a wave
      complex, together with an earlier and enhanced P3b. More interestingly,
      participants with non-clinical social anxiety manifested a reduced N2b wave when
      they had to detect a change in intensity of anger presentation. However, these
      individuals did not show facilitation to disengage from disgust when they have to
      detect angry faces, which was displayed by control participants. Implications and
      suggestions for further research about the role played by anger and disgust in
      psychopathology are outlined.

PMID- 17184748
TI  - Deprivation of mother-pup interaction by early weaning alters myelin formation in
      male, but not female, ICR mice.
AB  - We previously reported that early-weaned Balb/c mice develop a persistent
      increase in anxiety as well as aggression, and we suggested that deprivation of
      mother-pup interaction from postnatal days 15 to 21 might account for this
      phenomenon. In the present study, we investigated developmental changes in myelin
      formation and behavioral effects of early weaning in male and female ICR mice.
      Early weaning was associated with decreased numbers of open-arm entries in an
      elevated plus-maze for both male and female mice at 3 weeks of age (W3); this
      effect was persistently observed in males, but ceased after W3 in females.
      Compared to the brains of normally weaned mice, the brains of the early-weaned
      males at W8 and of the females at W5 were of lesser mass. Western blotting with
      whole-brain homogenates identified four isoforms of myelin basic protein (MBP;
      21.5, 18.5, 17.0, and 14.0 kDa). Expression of these MBPs increased gradually in
      normally weaned mice. In contrast, in the early-weaned male mice, but not the
      early-weaned female mice, it increased robustly at W3 and then declined at W5, as
      compared to the normally weaned mice. These results suggest that early weaning
      influences not only anxiety-related behavior but also myelin formation in the
      brain during the developmental period, particularly between 3 and 5 weeks of age,
      and male mice are more vulnerable than females to early-weaning effects on
      behavior and myelin formation.

PMID- 17184750
TI  - Morphine-induced place preference: involvement of the central amygdala NMDA
      receptors.
AB  - In the present study, the effects of bilateral injections of N-methyl-d-aspartate
      (NMDA) receptor agonist and/or antagonist into the central amygdala (CeA) on the
      acquisition and expression of morphine-induced conditioned place preference (CPP)
      were investigated in male Wistar rats. Animals that received 3 daily subcutaneous
      (s.c.) injections of morphine (1-9 mg/kg) or saline (1.0 ml/kg) indicated a
      significant preference for compartment paired with morphine in a dose dependent
      manner. Intra-CeA administration of the NMDA (0.01, 0.1 or 1 microg/rat) with an
      ineffective dose of morphine (1 mg/kg, s.c.) elicited a significant CPP.
      Administration of the non-competitive NMDA receptor antagonist, MK-801 (0.1, 0.3
      or 0.5 microg/rat), into the central amygdala dose-dependently inhibited the
      morphine (6 mg/kg, s.c.)-induced place preference. Furthermore, intra-CeA
      administration of MK-801 (0.25, 0.5 or 1 microg/rat) reduced the response induced
      by NMDA (1 microg/rat, intra-CeA) plus morphine (1 mg/kg, s.c.). Neither NMDA nor
      MK-801 alone produce a significant place preference or place aversion. Moreover,
      intra-CeA injection of NMDA but not MK-801 before testing significantly increased
      the expression of morphine (6 mg/kg, s.c.)-induced place preference. NMDA or MK
      801 injections into the CeA had no effects on locomotor activity on the testing
      sessions. These results suggest that the NMDA receptor mechanisms in the central
      amygdala may be involved in the acquisition and expression of morphine-induced
      place preference.

PMID- 17184749
TI  - Dietary supplementation with uridine-5'-monophosphate (UMP), a membrane
      phosphatide precursor, increases acetylcholine level and release in striatum of
      aged rat.
AB  - The biosynthesis of brain membrane phosphatides, e.g., phosphatidylcholine
      (PtdCho), may utilize three circulating compounds: choline, uridine (a precursor
      for UTP, CTP, and CDP-choline), and a PUFA (e.g., docosahexaenoic acid);
      moreover, oral administration of the uridine source uridine-5'-monophosphate
      (UMP) can significantly increase levels of the phosphatides throughout the rodent
      brain. Since PtdCho can provide choline for acetylcholine (ACh) synthesis, we
      determined whether UMP administration also affects ACh levels in striatum and
      striatal extracellular fluid, in aged and young rats. Among aged animals
      consuming a UMP-containing diet (2.5%, w/w) for 1 or 6 weeks, baseline ACh levels
      in striatal dialysates rose from 73 fmol/min to 148 or 197 fmol/min (P<0.05).
      Consuming a lower dose (0.5%) for 1 week produced a smaller but still significant
      increase (from 75 to 92 fmol/min, P<0.05), and elevated striatal ACh content (by
      16%; P<0.05). Dietary UMP (0.5%, 1 week) also amplified the increase in ACh
      caused by giving atropine (10 microM in the aCSF); atropine alone increased ACh
      concentrations from 81 to 386 fmol/min in control rats and from 137 to 680
      fmol/min in those consuming UMP (P<0.05). Young rats eating the UMP-containing
      diet exhibited similar increases in basal ECF ACh (from 105 to 118 fmol/min) and
      in the increase produced by atropine (from 489 to 560 fmol/min; P<0.05). These
      data suggest that giving a uridine source may enhance some cholinergic functions,
      perhaps by increasing brain phosphatide levels.

PMID- 17184751
TI  - Diphenyleneiodonium and dimethylsulfoxide for treatment of reperfusion injury in
      cerebral ischemia of the rat.
AB  - Diphenyleneiodonium (DPI) is an inhibitor of the free radical producing NAD(P)H
      oxidase. We tested whether DPI shows neuroprotective properties after focal
      cerebral ischemia and we used dimethylsulfoxide (DMSO), a nonspecific free
      radical scavenger, as a solvent. In male Wistar rats middle cerebral artery
      occlusion (1.5 h) and subsequent reperfusion (48 h) (MCAO/R) was induced with the
      filament model. Immediately after reperfusion the animals received either 0.25 ml
      normal saline, DMSO, or a combination of DMSO and DPI; each group consisted of 10
      animals. MRI was performed at different times after reperfusion. Gelatine
      zymography of brain tissue for MMP-2 and MMP-9 was performed. The infarct sizes
      and BBB damage showed a significant difference between controls and the DPI/DMSO
      group for almost all points in time in all sequences. The activity of MMP-2 and
      MMP-9 was significantly reduced by DPI/DMSO but not by DMSO alone. DMSO treatment
      alone resulted in a protective effect with reduced lesion sizes measured by MRI
      at selected points of time, consistent with its known free radical scavenger
      effect. The combination of DMSO with DPI partly augmented this effect, presumably
      due to the additional inhibition of MMP-2 and MMP-9 by DPI. Moreover, the
      neurological outcome in both therapeutic groups was improved compared to controls
      with a significant difference between the therapeutic groups in favour of DPI and
      DMSO. The combination of DPI and DMSO reduced the activity of MMP-2 and MMP-9,
      attenuated the postischemic blood-brain barrier damage and improved neurological
      outcome. This was most likely due to reduced oxidative stress.

PMID- 17184752
TI  - Non-fluent progressive aphasia: cerebral metabolic patterns and brain reserve.
AB  - Functional imaging studies suggest that brain reserve allows patients with
      Alzheimer's disease with more years of schooling to cope better with brain
      damage. No studies exist on patients with non-fluent progressive aphasia (NFPA).
      We aimed to explore metabolic patterns of patients with NFPA and to provide
      evidence for brain reserve in NFPA. 11 right-handed patients with NFPA and 16 age
      matched controls underwent (18)F-FDG PET imaging. Scans of patients and controls
      were compared in SPM2. A linear regression analysis with glucose metabolism as
      dependent variable and years of schooling as the independent variable, adjusted
      for age, gender, and a total score of the CERAD neuropsychological battery was
      conducted. The NFPA group showed a hypometabolism of the left hemisphere
      including the middle frontal, and inferior temporal and angular gyri, and the
      bilateral caudate nuclei and thalami (p(corr)<0.05). The regression analysis
      revealed a significant inverse association between education and glucose
      metabolism in the left inferior temporal, parahippocampal, and supramarginal gyri
      (p(corr)<0.05). We conclude that brain reserve is also present in NFPA.

PMID- 17184753
TI  - Unilateral cortical application of interleukin-1beta (IL1beta) induces asymmetry
      in fos, IL1beta and nerve growth factor immunoreactivity: implications for sleep
      regulation.
AB  - Unilateral injection of interleukin-1 beta (IL1beta) into the somatosensory
      cortex enhances EEG slow wave activity ipsilaterally during non-rapid eye
      movement sleep [Yasuda, T., Yoshida, H., Garcia-Garcia, F., Kay, D., Krueger,
      J.M., 2005. Interleukin-1beta has a role in cerebral cortical state-dependent
      electroencephalographic slow-wave activity. Sleep 28, 177-184]. We show that a
      similar unilateral microinjection of IL1beta (10 ng) into layer VI or onto the
      surface of the primary somatosensory cortex induced increases in the neuronal
      activity marker, Fos, relative to the contralateral side that received saline or
      heat-inactivated IL1beta. When IL1beta was microinjected into layer VI, increases
      in Fos-immunoreactive nuclei were evident in layers II, III and VI of the
      somatosensory cortex and connected cortical regions, such as the endopiriform,
      secondary somatosensory, piriform and prefrontal cortex. Asymmetrical increases
      in Fos were also observed in subcortical regions, such as the reticular thalamus,
      which receives a main cortical projection, and hypothalamic regions implicated in
      sleep regulation, such as the ventrolateral preoptic area and dorsal median
      preoptic nucleus. Fos activation was not observed in many other brain regions. In
      the reticular thalamus and somatosensory cortex, the number of IL1beta
      immunoreactive glial cells increased. Further, the number of NGF-immunoreactive
      cells in the primary somatosensory cortex and magnocellular preoptic nucleus
      increased on the IL1beta-injected side. These results are consistent with the
      hypothesis that sleep is initiated within the cortex after the local activation
      of specific cytokines and that whole organism sleep is coordinated via cortical
      connections with the subcortical sites.

PMID- 17184754
TI  - Dopamine D1 and D2 receptors regulate extracellular lactate and glucose
      concentrations in the nucleus accumbens.
AB  - Glucose and lactate have been shown to play a significant role in energy
      metabolism in the brain. In the present study, the relationship between
      extracellular glucose and lactate concentrations in the nucleus accumbens (NAC)
      was determined with in vivo microdialysis technique. We further evaluated the
      effect of dopamine (DA) receptor agonists on energy metabolism. Extracellular
      glucose levels were increased following inactivation of neurons by tetrodotoxin
      (TTX) perfusion, whereas neural activation by veratridine or K(+) perfusion
      decreased extracellular glucose concentrations. By contrast, lactate levels were
      increased by veratridine or K(+) perfusion, but were unaltered by TTX.
      Apomorphine (0.05 mg/kg), a mixed D1/D2 receptor agonist, did not alter the
      extracellular glucose and lactate concentrations, while a higher dose (0.5 mg/kg)
      increased them. Bromocriptine, a selective D2 receptor agonist, increased
      extracellular glucose, but not lactate concentrations. These results indicate
      that extracellular lactate levels may be a more suitable indicator of acute
      neural activation than glucose levels, and that simultaneous stimulation of D1
      and D2 receptors enhances energy demands of DA neurons in the NAC.

PMID- 17184755
TI  - Differentiation of the anomeric configuration and ring form of glucosyl
      glycolaldehyde anions in the gas phase by mass spectrometry: isomeric
      discrimination between m/z 221 anions derived from disaccharides and chemical
      synthesis of m/z 221 standards.
AB  - Mass spectrometry of disaccharides in the negative-ion mode frequently generates
      product anions of m/z 221. With glucose-containing disaccharides, dissociation of
      isolated m/z 221 product ions in a Paul trap yielded mass spectra that easily
      differentiated between both anomeric configurations and ring forms of the ions.
      These ions were shown to be glucosyl-glycolaldehydes through chemical synthesis
      of their standards. By labeling the reducing carbonyl oxygen of disaccharides
      with 18O to mass discriminate between monosaccharides, it was established that
      the m/z 221 ions are comprised solely of an intact nonreducing sugar with a two
      carbon aglycon derived from the reducing sugar, regardless of the disaccharide
      linkage position. This enabled the anomeric configuration and ring form of the
      ion to be assigned and the location of the ion to the nonreducing side of a
      glycosidic linkage to be ascertained. Detailed studies of experimental factors
      necessary for reproducibility in a Paul trap demonstrated that the unique
      dissociation patterns that discriminate between the isomeric m/z 221 ions could
      be obtained from month-to-month in conjunction with an internal energy-input
      calibrant ion that ensures reproducible energy deposition into isolated m/z 221
      ions. In addition, MS/MS fragmentation patterns of disaccharide m/z 341 anions in
      a Paul trap enabled linkage positions to be assigned, as has been previously
      reported with other types of mass spectrometers.

PMID- 17184757
TI  - Recovery of neuropathy target esterase activity after inhibition with mipafox and
      O-hexyl O-2,5-dichlorophenyl phosphoramidate in bovine chromaffin cell cultures.
AB  - Neuropathy target esterase (NTE) is a membrane protein present in various tissues
      whose physiological function has been recently suggested to be the maintenance of
      phosphatidylcholine homeostasis. Inhibition and further modification of NTE by
      certain organophosphorus compounds (OPs) were related to the induction of the
      "organophosphorus induced delayed neuropathy". Bovine chromaffin cells were
      cultured at 75,000cells/well in 96-well plates and exposed to 25microM mipafox or
      3microM O-hexyl O-2,5-dichlorophenyl phosphoramidate (HDCP) for 60min. Inhibitors
      were removed by washing cells three times with Krebs solution. Then NTE activity
      was assayed at 0, 24, 48 and 120h after exposure using the Biomek 1000
      workstation. Immediately after mipafox treatment NTE activity represented 3% of
      the control (6.7+/-1.9mU/10(6) cells). At 24, 48 and 120h after removing
      inhibitor, recorded activities were 33%, 42% and 111% of their respective
      controls (5.7+/-3.1; 5.7+/-1.9; 5.4+/-0.0mU/10(6) cells, respectively). Treatment
      with HDCP also displayed a time-dependent pattern of NTE recovery. As NTE
      inhibited by phosphoramidates is not reactivated in homogenized tissues, these
      results confirm a time-dependent regeneration of NTE after inhibition by
      neuropathic OPs.

PMID- 17184756
TI  - Treatment of Brucella-susceptible mice with IL-12 increases primary and secondary
      immunity.
AB  - Brucella spp. cause disease in humans and livestock and are potential biowarfare
      agents. Defining the protective immune response is necessary to design vaccines.
      This has largely been done with mice, brucella-susceptible BALB/c and resistant
      C57BL strains. Since interferon-gamma is key to brucella resistance, contrary to
      expectations, we found that ex vivo splenocytes from naive BALB/c mice produced
      IL-12 and interferon-gamma in cultures with brucellae at levels comparable to
      those of splenocytes from the more resistant C57BL/10 mice. Moreover, both IL-12
      and interferon-gamma were produced in the first week following infection of
      BALB/c mice. However, by the third week of infection we found decreased IL
      12Rbeta2 expression by BABL/c splenocytes, corresponding to their inability to
      produce interferon-gamma in Brucella recall responses at this time as reported
      previously. Administering recombinant IL-12 to these mice ameliorated the
      interferon-gamma hiatus, resulted in a 1000-fold reduction in CFU during primary
      infection and increased survival following secondary challenge.

PMID- 17184759
TI  - Systemic analysis of the differential gene expression profile in a colonic
      adenoma-normal SSH library.
AB  - BACKGROUND: The discovery of differentially expressed genes of colonic adenoma
      minus normal mucosa enables the understanding of early molecular events in
      colorectal carcinogenesis. In our previous study, we have developed an adenoma
      minus normal mucosa suppression subtractive hybridization (SSH) library and
      identified 109 differentially expressed clones. METHODS: An in-house EST pipeline
      and the Gene Ontology web-based tool () were used to analyze these clones.
      Realtime quantitative RT-PCR (Q-PCR) was applied to detect the expression of 14-3
      3 zeta, REG4 and 6 ribosomal protein genes (RPS2, RPS12, RPS27A, RPL5, RPL7a and
      RPL10a) in 14 adenomas (8 with concurrent cancers) and 44 colorectal
      adenocarcinomas with paired normal mucosa. RESULTS: Sixty-two candidate genes
      were obtained from this library. Bioinformatics analysis indicated that both
      ribosomal protein genes and immune-related genes were enriched. REG4 was
      significantly upregulated in colorectal adenomas (medium fold: 1.676, p<0.05,
      Wilcoxon test) and 14-3-3 zeta in cancers (medium fold: 1.202, p<0.01, Wilcoxon
      test), as compared with those of paired normal mucosa. However, all ribosomal
      protein genes were not significantly overexpressed in colorectal adenomas or
      cancers. CONCLUSIONS: A differential gene expression profile in A-N SSH library
      may be helpful in understanding the molecular mechanism of colorectal cancer
      initiation and progression. REG4 and 14-3-3 zeta may be potential biomarkers for
      early colorectal cancer detection.

PMID- 17184758
TI  - Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia?
AB  - Pre-eclampsia (P-Ec) is a complex multisystem disorder of unknown aetiology
      reported to occur in about 6% to 8% of all pregnancies throughout the world. This
      disease is associated with fibrin deposition and occlusive lesions in placental
      vessels. Pro-thrombin activatable fibrinolysis inhibitor (pro-TAFI) is a
      relatively recently described glycoprotein that can be converted into its active
      form (TAFIa) by thrombin, thrombin-thrombomodulin and plasmin. TAFIa potentially
      inhibits fibrinolysis by removing C-terminal lysine and arginine residues from
      fibrin. These residues are required for adsorption of tissue-type plasminogen
      activator (t-PA) and plasminogen to fibrin. Therefore, TAFIa decreases plasmin
      formation and protects the fibrin clot against lysis. An increased of pro
      TAFI/TAFIa levels has been reported in some clinical conditions associated with
      thrombotic tendency, as type II diabetes mellitus, deep vein thrombosis and
      symptomatic artery disease. Few studies have investigated pro-TAFI/TAFIa in
      normal or complicated pregnancy but contrasting results were reported.
      Understanding the role of pro-TAFI/TAFIa in the pathogenesis of P-Ec can hold
      great promise for improving P-Ec management. In this context, a large-scale study
      evaluating plasma TAFI antigen and activity, its synthesis and metabolism in pre
      eclamptic women is required. Recently new selective TAFIa inhibitors have been
      developed. The design of a new therapy to treat and/or prevent P-Ec, based on
      successful use of TAFIa inhibitors, may have significant clinical ramifications.

PMID- 17184760
TI  - Double-blind evaluation and benchmarking of survival models in a multi-centre
      study.
AB  - Accurate modelling of time-to-event data is of particular importance for both
      exploratory and predictive analysis in cancer, and can have a direct impact on
      clinical care. This study presents a detailed double-blind evaluation of the
      accuracy in out-of-sample prediction of mortality from two generic non-linear
      models, using artificial neural networks benchmarked against a partial logistic
      spline, log-normal and COX regression models. A data set containing 2880 samples
      was shared over the Internet using a purpose-built secure environment called
      GEOCONDA (www.geoconda.com). The evaluation was carried out in three parts. The
      first was a comparison between the predicted survival estimates for each of the
      four survival groups defined by the TNM staging system, against the empirical
      estimates derived by the Kaplan-Meier method. The second approach focused on the
      accurate prediction of survival over time, quantified with the time dependent C
      index (C(td)). Finally, calibration plots were obtained over the range of follow
      up and tested using a generalization of the Hosmer-Lemeshow test. All models
      showed satisfactory performance, with values of C(td) of about 0.7. None of the
      models showed a systematic tendency towards over/under estimation of the observed
      survival at tau=3 and 5 years. At tau=10 years, all models underestimated the
      observed survival, except for COX regression which returned an overestimate. The
      study presents a robust and unbiased benchmarking methodology using a bespoke web
      facility. It was concluded that powerful, recent flexible modelling algorithms
      show a comparative predictive performance to that of more established methods
      from the medical and biological literature, for the reference data set.

PMID- 17184761
TI  - Perspectives in endoscopic cardiac surgery.
AB  - Surgical telemanipulators are obviously used in cardiac surgery to provide the
      surgeon in a confined space the same stereoscopic vision, full dexterity,
      unimpaired hand-eye alignment and tactile feedback as in open surgery. This is
      the basic concept that enables the controlled fine soft tissue manipulation that
      is needed in bypass grafting and valve surgery. In 2005, a total of 2984 cardiac
      procedures were performed worldwide using the da Vinci system. This includes
      totally endoscopic coronary artery bypass grafting (TECAB), mitral valve repair
      (MVR) procedures, ASD closure and cardiac tissue ablation for atrial
      fibrillation.

PMID- 17184762
TI  - Parametric sensitivity analysis applied to a specific one-dimensional internal
      bone remodelling problem.
AB  - The relative importance of the various parameters in inducing bone mass loss and
      osteoclastic perforations is still controversial. Therefore, there is a
      significant motivation to better understand the parameters behind such dynamic
      response, and great interest to carry out a parametric sensitivity study as it
      can provide useful information. As an application, the widely-accepted bone
      remodelling equation [M.G. Mullender, R. Huiskes, H. Weinans, A physiological
      approach to the simulation of bone remodeling as self organizational control
      process, J. Biomech. 27 (1994) 1389.] is investigated using the "n units" model
      [M. Zidi, S. Ramtani, Bone remodeling theory applied to the study of n unit
      elements model, J Biomech. 32 (1999) 743.]. This analysis pointed out that the
      power in the modulus density relationship p and the power to which density is
      raised in normalizing the energy stimulus q, known as strongly implicated in the
      stability condition of the remodelling process, were also stated as insensitive
      parameters in the bone loss area.

PMID- 17184763
TI  - PubMed vs. HighWire Press: a head-to-head comparison of two medical literature
      search engines.
AB  - PubMed and HighWire Press are both useful medical literature search engines
      available for free to anyone on the internet. We measured retrieval accuracy,
      number of results generated, retrieval speed, features and search tools on
      HighWire Press and PubMed using the quick search features of each. We found that
      using HighWire Press resulted in a higher likelihood of retrieving the desired
      article and higher number of search results than the same search on PubMed.
      PubMed was faster than HighWire Press in delivering search results regardless of
      search settings. There are considerable differences in search features between
      these two search engines.

PMID- 17184764
TI  - Retinoids control anterior and dorsal properties in the developing forebrain.
AB  - We have previously shown that retinoic acid (RA) synthesized by the retinaldehyde
      dehydrogenase 2 (RALDH2) is required in forebrain development. Deficiency in RA
      due to inactivation of the mouse Raldh2 gene or to complete absence of retinoids
      in vitamin-A-deficient (VAD) quails, leads to abnormal morphogenesis of various
      forebrain derivatives. In this study we show that double Raldh2/Raldh3 mouse
      mutants have a more severe phenotype in the craniofacial region than single null
      mutants. In particular, the nasal processes are truncated and the eye
      abnormalities are exacerbated. It has been previously shown that retinoids act
      mainly on cell proliferation and survival in the ventral forebrain by regulating
      SHH and FGF8 signaling. Using the VAD quail model, which survives longer than the
      Raldh-deficient mouse embryos, we found that retinoids act in maintaining the
      correct position of anterior and dorsal boundaries in the forebrain by modulating
      FGF8 anteriorly and WNT signaling dorsally. Furthermore, BMP4 and FGF8 signaling
      are affected in the nasal region and BMP4 is ventrally expanded in the optic
      vesicle. At the optic cup stage, Pax6, Tbx5 and Bmp4 are ectopically expressed in
      the presumptive retinal pigmented epithelium (RPE), while Otx2 and Mitf are not
      induced, leading to a dorsal transdifferentiation of RPE to neural retina.
      Therefore, besides being required for survival of ventral structures, retinoids
      are involved in restricting anterior identity in the telencephalon and dorsal
      identity in the diencephalon and the retina.

PMID- 17184765
TI  - Neural retinal regeneration in the anuran amphibian Xenopus laevis post
      metamorphosis: transdifferentiation of retinal pigmented epithelium regenerates
      the neural retina.
AB  - In urodele amphibians like the newt, complete retina and lens regeneration occurs
      throughout their lives. In contrast, anuran amphibians retain this capacity only
      in the larval stage and quickly lose it during metamorphosis. It is believed that
      they are unable to regenerate these tissues after metamorphosis. However,
      contrary to this generally accepted notion, here we report that both the neural
      retina (NR) and lens regenerate following the surgical removal of these tissues
      in the anuran amphibian, Xenopus laevis, even in the mature animal. The NR
      regenerated both from the retinal pigment epithelial (RPE) cells by
      transdifferentiation and from the stem cells in the ciliary marginal zone (CMZ)
      by differentiation. In the early stage of NR regeneration (5-10 days post
      operation), RPE cells appeared to delaminate from the RPE layer and adhere to the
      remaining retinal vascular membrane. Thereafter, they underwent
      transdifferentiation to regenerate the NR layer. An in vitro culture study also
      revealed that RPE cells differentiated into neurons and that this was accelerated
      by the presence of FGF-2 and IGF-1. The source of the regenerating lens appeared
      to be remaining lens epithelium, suggesting that this is a kind of repair process
      rather than regeneration. Thus, we show for the first time that anuran amphibians
      retain the capacity for retinal regeneration after metamorphosis, similarly to
      urodeles, but that the mode of regeneration differs between the two orders. Our
      study provides a new tool for the molecular analysis of regulatory mechanisms
      involved in retinal and lens regeneration by providing an alternative animal
      model to the newt, the only other experimental model.

PMID- 17184766
TI  - The Notch signaling pathway in the cnidarian Hydra.
AB  - Many of the major pathways that govern early development in higher animals have
      been identified in cnidarians, including the Wnt, TGFbeta and tyrosine kinase
      signaling pathways. We show here that Notch signaling is also conserved in these
      early metazoans. We describe the Hydra Notch receptor (HvNotch) and provide
      evidence for the conservation of the Notch signaling mode via regulated
      intramembrane proteolysis. We observed that nuclear translocation of the Notch
      intracellular domain (NID) was inhibited by the synthetic gamma-secretase
      inhibitor DAPT. Moreover, DAPT treatment of hydra polyps caused distinct
      differentiation defects in their interstitial stem cell lineage. Nerve cell
      differentiation proceeded normally but post-mitotic nematocyte differentiation
      was dramatically reduced. Early female germ cell differentiation was inhibited
      before exit from mitosis. From these results we conclude that gamma-secretase
      activity and presumably Notch signaling are required to control differentiation
      events in the interstitial cell lineage of Hydra.

PMID- 17184767
TI  - Effect of ventilation rate on gradient of aerial contaminants in the confinement
      pig building.
AB  - The principal aim of this study was to compare the aerial contaminants
      concentrations between the levels of ventilation rate and determine the variation
      pattern of aerial contaminants affected by the ventilation rate. As a result,
      there was not significant difference in total dust and total airborne
      microorganisms among three levels of ventilation rate (P>0.05) whereas the
      increased ventilation rate lowered the levels of respirable dust and gaseous
      compounds (P<0.05). Based on the results, it was concluded that the suspended
      gases in the confinement pig building generally followed the air streamline
      formed by the ventilation whereas the ventilation rate had little effect on the
      gradient of particulates, especially total dust, due to gravity generated by
      their size and weight. The findings that the concentrations of total airborne
      microorganisms were not also significantly different among the ventilation rates
      could be explained in terms of the fact that airborne microorganisms are easily
      adsorbed on the surface of dust particle.

PMID- 17184768
TI  - The anti-inflammatory flavones quercetin and kaempferol cause inhibition of
      inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and
      down-regulation of the nuclear factor kappaB pathway in Chang Liver cells.
AB  - We examined the ability of the flavonoids quercetin and kaempferol to modulate
      inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and reactive C
      protein (CRP) expression, and to induce changes in the nuclear factor kappa B (NF
      kappaB) pathway in the human hepatocyte-derived cell line Chang Liver. Cells were
      incubated with a cytokine mixture supplemented with quercetin or kaempferol (5 to
      200 micromol/l). Kaempferol produced a significant concentration-dependent
      decrease of iNOS, COX-2 and CRP protein level at all concentrations, but the
      percentage of inhibition induced by quercetin was reduced at high concentrations.
      Both flavonoids significantly inhibited mRNA level of iNOS, COX-2, and CRP.
      Inhibitory effects by quercetin and kaempferol were also observed on NF-kappaB
      activation and on protein concentration of the phosphorylated form of the
      inhibitor IkappaB alpha and of IKK (IkappaB kinase)alpha. The present study
      suggests that the modulation of iNOS, COX-2 and CRP by quercetin or kaempferol
      may contribute to the anti-inflammatory effects of these two structurally similar
      flavonoids in Chang Liver cells, via mechanisms likely to involve blockade of NF
      kappaB activation and the resultant up-regulation of the pro-inflammatory genes.
      Our data also indicate that the minor structural differences between both
      compounds determine differences in their inhibitory capacity.

PMID- 17184769
TI  - Mechano-transduction mediated secretion and uptake of galectin-3 in breast
      carcinoma cells: implications in the extracellular functions of the lectin.
AB  - In the following experiments, we sought to understand the triggering mechanism
      which propels galectin-3 to be secreted into the extracellular compartment from
      its intracellular stores in breast carcinoma cells. We also wanted to analyze in
      greater details the role of galectin-3 in cellular adhesion and spreading. To do
      this, we made use of two pairs of breast carcinoma cell lines where one of the
      pair has high expression of galectin-3 and the other low expression of the
      lectin. We determined that galectin-3 secreted into the conditioned medium of sub
      confluent and spread cells in culture was quite low, almost negligible. However,
      once the cells were detached and rounded up, a mechano-sensing mechanism
      triggered the rapid secretion of galectin-3 into the conditioned medium. The
      secretion was constitutive as long as the cells remained detached. Galectin-3 was
      shown to be actively taken up from the conditioned medium by spreading cells. The
      cells which express and secrete high levels of galectin-3 adhered and spread much
      faster on plastic than those with reduced expression. The uptake of galectin-3
      according to our data was important in cell spreading because if this process was
      compromised significantly, cells failed to spread. The data suggested that
      galectin-3 uptake modulates the adhesion plaques in that cells which express high
      levels of galectin-3 have thin-dot like plaques that may be suited for rapid
      adhesion and spreading while cells in which galectin-3 expression is reduced or
      knocked-down, have thick and elongated plaques which may be suited for a firmer
      adhesion to the substratum. Recombinant galectin-3 added exogenously reduced the
      thickness of the adhesion plaques of tumor cells with reduced galectin-3
      expression. Taken together, the present data suggest that galectin-3 once
      externalized, is a powerful modulator of cellular adhesion and spreading in
      breast carcinoma cells.

PMID- 17184771
TI  - Role of cofactors B (TBCB) and E (TBCE) in tubulin heterodimer dissociation.
AB  - Tubulin folding cofactors B (TBCB) and E (TBCE) are alpha-tubulin binding
      proteins that, together with Arl2 and cofactors D (TBCD), A (TBCA or p14) and C
      (TBCC), participate in tubulin biogenesis. TBCD and TBCE have also been
      implicated in microtubule dynamics through regulation of tubulin heterodimer
      dissociation. Understanding the in vivo function of these proteins will shed
      light on the Kenny-Caffey/Sanjad-Sakati syndrome, an important human disorder
      associated with TBCE. Here we show that, when overexpressed, TBCB depolymerizes
      microtubules. We found that this function is based on the ability of TBCB to form
      a binary complex with TBCE that greatly enhances the efficiency of this cofactor
      to dissociate tubulin in vivo and in vitro. We also show that TBCE, TBCB and
      alpha-tubulin form a ternary complex after heterodimer dissociation, whereas the
      free beta-tubulin subunit is recovered by TBCA. These complexes might serve to
      escort alpha-tubulin towards degradation or recycling, depending on the cell
      requirements.

PMID- 17184770
TI  - Phosphoinositide 3-kinase regulates the role of retromer in transcytosis of the
      polymeric immunoglobulin receptor.
AB  - Retromer is a multimeric protein complex that mediates intracellular receptor
      sorting. One of the roles of retromer is to promote transcytosis of the polymeric
      immunoglobulin receptor (pIgR) and its ligand polymeric immunoglobulin A (pIgA)
      in polarized epithelial cells. In Madin-Darby Canine Kidney (MDCK) cells,
      overexpression of Vps35, the retromer subunit key for cargo recognition, restores
      transcytosis to a pIgR mutant that is normally degraded. Here we show that pIgA
      transcytosis was not restored in these cells when treated with the specific
      phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Likewise, the decrease in
      pIgA transcytosis by wild-type pIgR seen upon PI3K inhibition was not reverted by
      Vps35 overexpression. PI3K inhibition reduced membrane association of sorting
      nexins (SNX) 1 and 2, which constitute the retromer subcomplex involved in
      membrane deformation, while association of the Vps35-Vps26-Vps29 subcomplex,
      involved in cargo recognition, remained virtually unaffected. Colocalization
      between the two retromer subcomplexes was reduced upon the treatment. Whereas the
      interaction among the subunits of the Vps35-Vps26-Vps29 subcomplex remained
      unchanged, less Vps35 was found associated with pIgR upon PI3K inhibition. In
      addition, colocalization of internalized pIgA with subunits of both retromer
      subcomplexes throughout the transcytotic pathway was substantially reduced by
      LY294002 treatment. These data implicate PI3K in controlling retromer's role in
      pIgR-pIgA transcytosis.

PMID- 17184772
TI  - Deletion of the N-terminus of IKKgamma induces apoptosis in keratinocytes and
      impairs the AKT/PTEN signaling pathway.
AB  - The regulatory subunit IKKgamma/NEMO is crucial for skin development and function
      and although devoid of kinase activity, loss of IKKgamma function completely
      abolishes the activation of NF-kappaB by all pro-inflammatory cytokines. To
      inhibit the IkappaB kinase (IKK) complex in keratinocytes, we have used a
      dominant negative approach by generating stable transfectants of an N-terminal
      deletion of IKKgamma (IKKgamma-DN97) that uncouples formation of the IKK complex.
      Expression of this mutant in PB keratinocytes (PB-IKKgamma-DN97) delayed growth
      kinetics, caused morphological changes and dramatically augmented apoptosis even
      in the absence of pro-apoptotic stimuli, as determined by cell morphology, TUNEL
      and caspase-3 cleavage. Moreover, in PB-IKKgamma-DN97 cells, TNF-alpha and IL-1
      treatment failed to induce degradation of IkappaBalpha, phosphorylation of p65 on
      Ser 536 and nuclear translocation which, consequently, reduced kappaB-binding
      activity. In PB-IKKgamma-DN97 cells, accumulation of IkappaBalpha correlated with
      a downregulation of AKT activity and an increase of PTEN protein levels whereas
      pro-apoptotic p53 target genes Bax and Puma were upregulated. These effects were
      most likely mediated through IKK since coexpression of the wild-type form of
      IKKgamma in keratinocytes partially reversed apoptosis and reduced PTEN
      expression. Thus, our data suggest a negative cross-talk mechanism involving PTEN
      and NF-kappaB, critical for the anti-apoptotic role of NF-kappaB in
      keratinocytes.

PMID- 17184773
TI  - The role of uninjured C-afferents and injured afferents in the generation of
      mechanical hypersensitivity after partial peripheral nerve injury in the rat.
AB  - This study was performed to determine which of uninjured lumbar 4 (L4) C
      afferents and injured L5 afferents was important for the generation of mechanical
      hypersensitivity following L5 spinal nerve ligation-and-cut (SNLC, modified
      spinal nerve ligation) in the rat. The mechanical hypersensitivity established
      following L5 SNLC was completely abolished 6 weeks after local capsaicin
      treatment of the sciatic nerve or L4 spinal nerve. At this stage, a substantial
      number of capsaicin-sensitive C-afferents were eliminated without any loss of A
      afferents in the L4 spinal segment, suggesting that the capsaicin-sensitive L4 C
      afferents are a major contributor to L5 SNLC-produced mechanical
      hypersensitivity. The peripheral terminals of L4 C-afferents are active in
      maintaining mechanical hypersensitivity, even long after L5 SNLC. When capsaicin
      sensitive L4 C-afferents were previously eliminated, the induction of L5 SNLC
      produced hypersensitivity was partly prevented. Thus, capsaicin-sensitive L4 C
      afferents are crucial for the induction and maintenance of mechanical
      hypersensitivity in the L5 SNLC model. Also, when capsaicin-sensitive L4 C
      afferents were previously eliminated, L5 SNLC still produced a partial mechanical
      hypersensitivity for a 1- to 2-week maintenance period with a several-day delay.
      This mild hypersensitivity was prevented by the previous L5 dorsal rhizotomy,
      implying an involvement of inputs from injured L5 afferents in the maintenance of
      hypersensitivity at the earlier stage. The results suggest that uninjured C
      afferents, most likely C-polymodal nociceptors, are necessary for the induction
      and maintenance of neuropathic pain, and that afferent inputs, presumably from
      injured Abeta-fibers, also contribute to the maintenance at an earlier stage.

PMID- 17184775
TI  - Interaction mode of a symmetric Trp-rich undeca peptide PST11-RK with lipid
      bilayers.
AB  - To better understand the mode of action of the antimicrobial peptide PST11-RK, we
      investigated its (1) bactericidal kinetics, (2) ability to induce bacterial
      membrane depolarization, (3) ability to bind to liposomes, (4) cis/trans prolyl
      isomerization, (5) lipid binding kinetics and (6) translocation across lipid
      bilayers. Our findings suggest that PST11-RK acts mainly by collapsing the
      cytoplasmic membrane potential; it first attaches to the membrane via cationic C-
      and N-terminal residues and then inserts its central hydrophobic residues into
      the lipid interior. In addition, it seems likely that cis/trans isomerization
      facilitates the translocation of PST11-RK across the lipid bilayer, where it may
      interact with secondary intracellular targets.

PMID- 17184774
TI  - Diphenyleneiodonium induces ROS-independent p53 expression and apoptosis in human
      RPE cells.
AB  - The diphenyleneiodonium (DPI) is widely used as an inhibitor of flavoenzymes,
      particularly NADPH oxidase. In this study, we investigated the effect of DPI on
      the apoptosis of human RPE cells. DPI treatment in ARPE-19 cells evoked a dose-
      and time-dependent growth inhibition, and also induced DNA fragmentation and
      protein content of the proapoptotic factor Bax. In addition, DPI significantly
      induced the expression and phosphorylation of p53, which induces proapoptotic
      genes in response to DNA damage or irreparable cell cycle arrest. ROS have been
      implicated as a key factor in the activation of p53 by many chemotherapeutic
      drugs. Recent data on the regulation of intracellular ROS by DPI are
      controversial. Therefore, we analyzed whether DPI could contribute to the
      generation of intracellular ROS. Although there was increase in ROS level from
      cells treated for 24h with DPI, it was not detectable at early time points,
      required to induce p53 expression. And DPI-induced p53 expression was not
      affected by the ROS scavenger NAC. We conclude that DPI induces the expression of
      p53 by ROS-independent mechanism in ARPE-19 cells, and renders cells sensitive to
      drug-induced apoptosis by induction of p53 expression.

PMID- 17184776
TI  - Sporulating bacteria prefers predation to cannibalism in mixed cultures.
AB  - Predatory behavior, a property associated with ecosystems, is not commonly
      observed in microorganisms. However, cannibalistic tendencies have been observed
      in microorganisms under stress. For example, pure culture of Bacillus subtilis
      exhibits cannibalism under nutrient limitation. It has been proposed that a
      fraction of cells in the population produce Spo0A, a regulatory protein that is
      responsible for delaying sporulation. Cells containing spo0A would produce a
      killing factor by activating skf operon and an associated pump to export the
      factor. Cells that do not contain spo0A in the population are lysed. However in
      addition to the competition among the cells of B. subtilis, these cells also
      compete with other organisms for the limited nutrients. In this work, we report
      the cannibalistic behavior of B. subtilis in presence of Escherichia coli under
      severe nutritional limitation. We demonstrate that B. subtilis lyses cells of E.
      coli using an antibacterial factor under the regulation of Spo0A. Our experiments
      also suggest that B. subtilis prefers predation of E. coli to cannibalism in
      mixed cultures. B. subtilis also demonstrated predation in mixed cultures with
      other soil microorganisms, such as, Xanthomonas campestris, Pseudomonas
      aeruginosa and Acinetobactor lwoffi. This may offer B. subtilis a niche to
      survive in an environment with limited nutrients and under competition from other
      microorganisms.

PMID- 17184777
TI  - C. elegans RBX-2-CUL-5- and RBX-1-CUL-2-based complexes are redundant for
      oogenesis and activation of the MAP kinase MPK-1.
AB  - Cul5-based complex is a member of ECS (Elongin B/C-Cul2/Cul5-SOCS-box protein)
      ubiquitin ligase family. The cellular function of the Cul5-based complex is
      poorly understood. In this study, we found that oocyte septum formation and egg
      production did not occur in either cul-5- or rbx-2-depleted cul-2 homozygotes,
      although control cul-2 homozygotes laid approximately 50 eggs. These phenotypes
      are reminiscent of those caused by the MAP kinase mpk-1 depletion. In fact,
      activation of MPK-1 was significantly inhibited in cul-5-depleted cul-2 mutant
      and cul-2-depleted cul-5 mutant. Yeast two-hybrid analysis and RNAi-knockdown
      experiments suggest that oocyte maturation from pachytene exit and MPK-1
      activation are redundantly controlled by the RBX-2-CUL-5- and RBX-1-CUL-2-based
      complexes.

PMID- 17184778
TI  - Antibacterial cathelicidin peptide CAP11 suppresses the anandamide production
      from lipopolysaccharide-stimulated mononuclear phagocytes.
AB  - The action of antibacterial cathelicidin peptide CAP11 on the anandamide
      production from mononuclear phagocytes was examined. Lipopolysaccharide (LPS)
      stimulation induced the anandamide production from macrophage-like RAW264.7,
      accompanied with the enhanced anandamide-synthesizing enzyme activity; however,
      the anandamide-degrading enzyme activity was not changed by LPS-stimulation.
      Importantly, CAP11 suppressed the LPS-induced anandamide production and the
      increase of anandamide-synthesizing enzyme activity. Furthermore, CAP11 abrogated
      the LPS-binding to CD14-positive RAW264.7. These observations indicate that CAP11
      inhibits the binding of LPS to CD14-positive mononuclear phagocytes, thereby
      suppressing the anandamide synthesizing enzyme activity and the anandamide
      production from the cells.

PMID- 17184779
TI  - Identification of differential proteins in nasopharyngeal carcinoma cells with
      p53 silence by proteome analysis.
AB  - Although mutation of p53 tumor-suppressor gene is rare in nasopharyngeal
      carcinoma (NPC), NPC has a high frequency of overexpression of p53 protein. There
      seem to be complex mechanisms of inactivation and stabilization of p53 in NPC. To
      detect proteins associated with the function of p53 in high throughout screening,
      we succeeded in establishing p53 knockdown human NPC CNE2 cell line (CNE2sip53)
      using stable RNA interference, and compared the proteomic changes between
      CNE2sip53 and control cell line CNE2/pSUPER using two-dimensional gel
      electrophoresis. Twenty-two differentially expressed proteins between the two
      cell lines were identified by both matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry and electrospray ionization tandem mass
      spectrometry, some of which are known to be associated with the p53 function
      (HSP27, hnRNP K, 14-3-3sigma, etc.), and others may be novel proteins associated
      with p53 function (eIF4B, TPT1, hnRNP H3, SFRS1 etc.). Furthermore, several
      differential proteins including HSP27, HSP70, GRP75 and GRP78 were verified as
      p53 interacting proteins in NPC by immunoprecipitation and Western blot analysis,
      and the suppression of HSP27 expression by HSP27 antisense oligonucleotides could
      decrease the p53 protein level. Our data suggest that these differential proteins
      may be associated with the function of p53 in NPC, and provide new clues to
      elucidate the mechanisms of inactivation and stabilization of p53 in NPC.

PMID- 17184780
TI  - Frog ANP increases the amiloride-sensitive Na(+) channel activity in urinary
      bladder cells of Japanese tree frog, Hyla japonica.
AB  - We examined the mechanism of amiloride-sensitive Na(+) channels (ENaC) activated
      by fANP in epithelial cells of frog urinary bladder by using a cell-attached
      patch-clamp technique. ENaC activities in the epithelial cells were significantly
      increased following administration of both 10(-9)M fANP and 10(-5)M 8-Br-cGMP.
      Both fANP and 8-Br-cGMP, however, failed to activate the ENaC in the presence of
      10(-6)M amiloride. In addition, 8-Br-cGMP failed to activate the ENaC in the
      presence of a PKA inhibitor, KT-5720. In the next experiment, we measured both
      cGMP and cAMP production levels after treatment of fANP on the frog urinary
      bladder cells. Frog ANP significantly increased cGMP production, but not the cAMP
      production. Taken together, these results suggest that fANP activates ENaC
      through increases in cGMP production and activation of PKA.

PMID- 17184781
TI  - Can the "challenge hypothesis" be applied to insects?
AB  - The challenge hypothesis, conceived for testosterone and vertebrates, has
      recently been applied to juvenile hormone (JH) and insects. Scott [Scott, M.P.,
      2006a. Resource defense and juvenile hormone: the "challenge hypothesis" extended
      to insects. Horm. Behav. 49, 276-281] found that JH in the burying beetle
      Nicrophorus orbicollis increased in response to a social challenge in the
      presence of a breeding resource, while there was no such JH response in the
      purported brood parasite Nicrophorus pustulatus. Two important implications of
      the challenge hypothesis that need to be tested are whether JH affects dominance
      and why there are interspecific differences in the JH response to a social
      challenge. The effect of JH on dominance in burying beetles was examined by
      topical application of JH III to one of two competing females at 24 h and again
      at 1 h prior to presentation of a breeding resource (mouse carcass). JH
      supplementation had no effect on dominance in intraspecific interactions in N.
      orbicollis, as measured by possession of the carcass on Day 1, 3 or 7. Similarly,
      JH did not alter carcass ownership during competition between N. orbicollis and
      N. pustulatus nor did it affect reproductive success. Irrespective of JH
      supplementation, N. pustulatus became increasingly dominant as the trials
      progressed, rarely occupying the carcass on Day 1, but excluding N. orbicollis in
      nearly half the trials by Day 7. These findings, and a brief review of the
      burying beetle literature, suggest that the challenge hypothesis, as applied to
      testosterone and vertebrates, does not yet have an analogous model for JH and
      insects.

PMID- 17184783
TI  - Does additional support by nurses enhance the effect of a brief smoking cessation
      intervention in people with moderate to severe chronic obstructive pulmonary
      disease? A randomised controlled trial.
AB  - BACKGROUND: Smoking cessation is the primary disease modifying intervention for
      chronic obstructive pulmonary disease (COPD). SETTING: A Regional Respiratory
      Centre (RRC) out-patient department in Northern Ireland. METHODS: A randomised
      controlled trial (RCT) evaluated the effectiveness of brief advice alone or
      accompanied by individual nurse support or group support facilitated by nurses.
      Smoking status was biochemically validated and stage of change, nicotine
      addiction and dyspnoea were recorded at 2, 3, 6, 9 and 12 months. PARTICIPANTS:
      Ninety-one cigarette smokers with COPD were enrolled in the study (mean age 61
      years, 47 female). RESULTS: After 12 months cessation rates were not
      significantly different between groups (p=0.7), but all groups had a significant
      reduction in their nicotine addiction (p=0.03-0.006). No changes in subjects'
      motivation or dyspnoea were detected over the 12 months. CONCLUSION: Patients
      with COPD were unable to stop smoking regardless of the type of support they
      received. Harm reduction may be a more appropriate goal than complete cessation
      for intractable smokers and nurses must evaluate their role in this arena.

PMID- 17184782
TI  - Dominant-subordinate relationships in hamsters: sex differences in reactions to
      familiar opponents.
AB  - In the majority of mammalian species, males are dominant over and more aggressive
      than females. In contrast, some reports suggest that female golden hamsters are
      more aggressive than males but systematic comparisons using the same methods for
      both sexes are rare. We observed same-sexed pairs of hamsters over repeated
      trials to assess whether sex differences existed in the level of agonistic
      behavior and in the development and maintenance of dominant-subordinate
      relationships with familiar partners. There were no sex differences in measures
      of agonistic behavior or fear responses (fleeing) during the initial series of
      three trials on the first day of testing. Following a four-day interval, males
      that had lost in session 1 showed fearful responses to a familiar dominant male
      and were not likely to engage in a fight with him. In contrast, females that lost
      the initial fights were not fearful and fought vigorously with the familiar
      winner in subsequent encounters. Although the amount of agonistic behavior
      engaged in by females did decrease over the course of the three sessions, females
      that lost did not demonstrate an increase in fear, as measured by the latency to
      flee. Males that lost fights did show increased fear during later trials and
      sessions. These results suggest that female hamsters are less affected by losing
      fights than males are and thus that females are less likely than males to develop
      highly polarized dominant-subordinate relationships. Further work is needed to
      understand the mechanisms underlying these sex differences.

PMID- 17184785
TI  - Determination of imidazole and triazole fungicide residues in honeybees using gas
      chromatography-mass spectrometry.
AB  - An analytical method employing clean up by high-performance gel permeation
      chromatography (HPGPC) and solid-phase extraction (SPE) on Florisil cartridges
      was developed to determine residues of eleven imidazole and triazole ergosterol
      biosynthesis-inhibiting (EBI) fungicides in honeybee samples. Detection was by
      means of gas chromatography-mass spectrometry (GC-MS) in selected ion monitoring
      (SIM) mode. The method was validated by fortifying control samples at levels of
      0.01 and 0.05 micro g/bee. Mean recoveries for each analyte except imazalil were
      between 79 and 99% with relative standard deviations of 12.3% or less. Mean
      recoveries of imazalil were 51% at 0.01 micro g/bee and 81% at 0.05 micro g/bee.
      Limits of detection for the analytes investigated ranged from 0.005 to 0.001
      micro g/bee.

PMID- 17184784
TI  - Development of an on-line high performance liquid chromatography detection system
      for human cytochrome P450 1A2 inhibitors in extracts of natural products.
AB  - An on-line HPLC screening method for detection of inhibitors of human cytochrome
      P450 1A2 in extracts was developed. HPLC separation of extracts is connected to a
      continuous methoxyresorufin-O-demethylation (MROD) assay in which recombinant
      human P450 1A2 converts methoxyresorufin to its fluorescent metabolite resorufin.
      The system was tested with three P450 1A2 inhibitors, for which minimum
      detectable amounts (MDA) ranging from 0.7 to 9.5 ng were obtained. Analysis of a
      kava kava and a basil extract showed that the on-line system is applicable to
      complex mixtures, since in both extracts, peaks with P450 1A2 inhibiting activity
      were observed.

PMID- 17184786
TI  - Differential interactions of plasmid DNA, RNA and endotoxin with immobilised and
      free metal ions.
AB  - Separation of negatively charged molecules, such as plasmid DNA (pDNA), RNA and
      endotoxin forms a bottleneck for the development of pDNA vaccine production
      process. The use of affinity interactions of transition metal ions with these
      molecules may provide an ideal separation methodology. In this study, the binding
      behaviour of pDNA, RNA and endotoxin to transition metal ions, either in
      immobilised or free form, was investigated. Transition metal ions: Cu2+, Ni2+,
      Zn2+, Co2+ and Fe3+, typically employed in the immobilised metal affinity
      chromatography (IMAC), showed very different binding behaviour depending on the
      type of metal ions and their existing state, i.e. immobilised or free. In the
      alkaline cell lysate, pDNA showed no binding to any of the IMAC chemistries
      tested whereas RNA interacted significantly with Cu2+-iminodiacetic acid (IDA)
      and Ni2+-IDA but showed no substantial binding to the rest of the IMAC
      chemistries. pDNA and RNA, however, interacted to varying degrees with free metal
      ions in the solution. The greatest selectivity in terms of pDNA and RNA
      separation was achieved with Zn2+ which enabled almost full precipitation of RNA
      while keeping pDNA soluble. For both immobilised and free metal ions, ionic
      strength of solution affected the metal ion-nucleic acid interaction
      significantly. Endotoxin, being more flexible, was able to interact better with
      the immobilised metal ions than the nucleic acids and showed binding to all the
      IMAC chemistries. The specific interactions of immobilised and/or free metal ions
      with pDNA, RNA and endotoxin showed a good potential, by selectively removing RNA
      and endotoxin at high efficiency, to develop a simplified pDNA purification
      process with improved process economics.

PMID- 17184787
TI  - A novel method for preparing and characterizing alcoholic EPD suspensions.
AB  - Ceramic suspensions composed of alumina and mixtures of alumina and zirconia
      powders in ethyl alcohol were prepared. A solution of citric acid and
      triethylamine was used as dispersant. The citric acid, which usually is used as
      dispersant in water alumina suspensions, gave excellent results in ethyl alcohol
      also if it was used in conjunction with triethylamine. A novel method consisting
      of combined measurements of grain size, zeta potential, and transmittance was
      optimized to study the dispersion and stability properties of the ceramic
      suspensions; by using this method the optimal dispersant amount was determined.
      The suspensions based on alumina and alumina-zirconia powders were used to coat
      stainless steel plates by electrophoretic deposition (EPD); the optimal
      composition of suspensions and the used EPD parameters made it possible to obtain
      coatings with uniform thickness and composition.

PMID- 17184788
TI  - Liquid-vapor density profiles from equilibrium limit of diffusion equation for
      interacting particles.
AB  - Liquid-vapor density profiles are derived from the equilibrium limit of diffusion
      equation for interacting particles. These profiles are in good agreement with
      classical hyperbolic tangent relation. For simple Lennard-Jones fluids, predicted
      density distributions agree with computer simulation data, but have a slightly
      sharper transition zone. For alkali metals with Lennard-Jones-like potentials,
      the new equations predict a very good average distribution with quite
      satisfactory agreement with Monte Carlo simulation results. For liquid metals and
      water surfaces, accurate interfacial profile predictions also can be achieved by
      using effective two-body potential data instead of Lennard-Jones parameters.

PMID- 17184789
TI  - Formation of 2D colloidal crystals by the Langmuir-Blodgett technique monitored
      in situ by Brewster angle microscopy.
AB  - We report a method that combines Brewster angle microscopy and Langmuir-Blodgett
      films technique to obtain highly ordered 2D colloidal crystals of nanospheres.
      The deposition of Langmuir-Blodgett films of silica spheres monitored by Brewster
      angle microscopy allows to determine with accuracy the best physical conditions
      to transfer highly ordered monolayers of nanoparticles.

PMID- 17184790
TI  - Effect of added ionic liquid on aqueous Triton X-100 micelles.
AB  - Addition of ionic liquids to aqueous surfactant solutions can alter/modify
      physicochemical properties of such systems in favorable manner. Changes in the
      properties of aqueous solutions of a useful nonionic surfactant Triton X-100 (TX
      100) are assessed upon addition of 2.1 wt% of a common and popular ionic liquid 1
      butyl-3-methylimidazolium hexafluorophosphate (bmimPF6). It is shown that the
      solubility of 'hydrophobic' bmimPF6 in aqueous TX-100 increases with TX-100
      concentration. This observation combined with the conductivity data strongly
      indicates partitioning of bmimPF6 into TX-100 micellar phase. Behavior of a
      variety of molecular absorbance [methyl orange, phenol blue, and N,N-diethyl-4
      nitroaniline] and fluorescence [phenyl on the TX-100, pyrene, pyrene-1
      carboxaldehyde, 2-(p-toluidino)naphthalene-6-sulfonate, and 1,3-bis-(1
      pyrenyl)propane] probes further confirm this observation. Statistically
      insignificant increase in critical micelle concentration (cmc) and decrease in
      aggregation number (N(agg)) of TX-100 micelles are observed upon addition of 2.1
      wt% bmimPF6. Based on the overall data, it is inferred that ionic liquid bmimPF6
      partitions into the TX-100 micellar phase; presence of bmimPF6 both close to the
      core as well as in the palisade layer of TX-100 micelles is suggested. Presence
      of favorable interactions (e.g., H-bonding, dipole-induced dipole, among others)
      between bmimPF6 and TX-100 is proposed to be the reason for these observations.

PMID- 17184791
TI  - Beta3 integrin deficiency promotes cardiac hypertrophy and inflammation.
AB  - Cardiac hypertrophy commonly develops in response to pressure overload and is
      associated with increased mortality. Mechanical stress in the heart can result in
      the activation of transmembrane integrin alphabeta heterodimers that are
      expressed in cardiomyocytes. Once activated, integrins stimulate focal adhesion
      kinase, Grb2, c-src, and other signaling molecules to promote cardiomyocyte
      growth and gene expression. Mechanical stress can also promote cardiac
      inflammation that may be mediated, in part, by the activation of integrins
      expressed in blood-borne cells. To address the role of one integrin, beta(3), in
      the pathogenesis of cardiac hypertrophy, beta(3)(-/-) mice were examined.
      beta(3)(-/-) Mice developed moderate spontaneous cardiac hypertrophy associated
      with systolic and diastolic dysfunction, and these abnormalities were exacerbated
      by transverse aortic constriction. In addition, beta(3)(-/-) mice developed mild
      cardiac inflammation with infiltrating macrophages at baseline that was markedly
      worsened by pressure overload. Bone marrow transplantation experiments showed
      that blood-borne cells were at least partially responsible for the cardiac
      hypertrophy and inflammation observed in beta(3)(-/-) mice. These results suggest
      that alpha(v)beta(3) expression in bone marrow has a generalized suppressive
      effect on cardiac inflammation.

PMID- 17184792
TI  - Comparison of K+ currents in cardiac Purkinje cells isolated from rabbit and dog.
AB  - The repolarization reserve determines the ability of drugs to prolong the cardiac
      action potential duration. Differences in K(+) currents between rabbit and dog
      cardiac Purkinje cells were studied by recording the transient outward K(+)
      current (I(to)) as well as the delayed rectifier K(+) currents (I(Ks) and I(Kr))
      during repolarization. Purkinje fibers were dissected from dog and rabbit hearts
      and exposed to enzymatic digestion until isolated cells were obtained. Whole cell
      voltage clamp methods were used to measure K(+) currents in both cell types.
      Action potential (AP) recordings from Purkinje cells displayed a rapid phase 1
      repolarization due to a prominent I(to) with densities of 13.3+/-2.3 and 9.6+/
      0.6 pA/pF at +40 mV in dog and rabbit respectively. I(Ks) tail currents were
      significantly larger in dog Purkinje cells. I(Kr) tail current densities were
      comparable in Purkinje cell from both species. Rabbit ventricular and Purkinje
      cell AP waveforms were used for action potential clamp experiments in TSA201
      cells expressing human ether a go-go related gene (HERG). HERG currents elicited
      by the ventricular waveform reached its maximum amplitude during phase 3
      repolarization. In contrast, Purkinje cell AP waveform elicited markedly smaller
      HERG currents even though the action potential duration was longer. The
      observations suggest that the fast phase 1 and negative plateau of the Purkinje
      cell AP limits the contribution of I(Kr) to repolarization. These results provide
      evidence that rabbit Purkinje cells have a smaller repolarization reserve and
      provide a biophysical explanation for a previously observed higher sensitivity to
      QT prolonging drugs in rabbit than dog Purkinje fibers.

PMID- 17184793
TI  - Integrative models of bat rabies immunology, epizootiology and disease
      demography.
AB  - Bats are natural reservoirs of rabies. We address the maintenance of the disease
      in bat colonies by developing individual and population models that generate
      indicators of risk of rabies to bats, that provide dynamic estimates of effects
      of rabies on population densities, and that suggest consequences of viral
      exposures and infections in bats relative to physiological and ecological
      characteristics of bats in different habitats. We present individual models
      (within host) for the immune responses to a rabies virus challenge, an
      immunotypic disease model that describes the evolution of the disease and a
      disease demographics model, which is structured by immunotypic response governed
      by immune system efficiency. Model simulations are consistent with available
      data, characterized by relatively low prevalence of the virus in colonies and
      much higher prevalence of rabies virus-neutralizing antibodies. Under model
      conditions, there is a robust non-clinical state that can be attained by the
      exposed individual that allows persistence of the disease in the population.

PMID- 17184794
TI  - Letter to the editors regarding some papers of Dr. Satoshi Kanazawa.

PMID- 17184795
TI  - Hermaphroditism: What's not to like?
AB  - Hermaphroditism is rare and phylogenically in decline among animal species. The
      evolutionary basis for this development is not well understood. This paper
      focusses on self-incompatible simultaneous hermaphroditism in animals. It
      proposes that such hermaphroditism is not stable in sufficiently heterogeneous
      populations, suggesting a possible reason for why hermaphroditism is rare among
      evolved animal species. The argument turns on the Bateman principle, namely that
      male reproductive success (RS) is limited by partner availability, while female
      RS is not. We show that: low-quality individuals do better if female; secondary
      sexual differentiation may be important for understanding the existence of males;
      and that hermaphroditic mating is reciprocal. Reciprocity may be key to
      understanding promiscuity and attendant phenomena such as cryptic female choice,
      sperm competition and love darts-common features of hermaphroditic mating. We
      also argue that hermaphrodites are especially vulnerable to male violence,
      suggesting a reason for the rarity of trioecy. Finally, we propose that external
      fertilization, and the scope for streaking, may be one reason fish are the only
      simultaneously hermaphroditic vertebrates.

PMID- 17184796
TI  - Protocell self-reproduction in a spatially extended metabolism-vesicle system.
AB  - Cellular life requires the presence of a set of biochemical mechanisms in order
      to maintain a predictable process of growth and division. Several attempts have
      been made towards the building of minimal protocells from a top-down approach,
      i.e. by using available biomolecules. This type of synthetic approach has so far
      been only partially successful, and appropriate models of the synthetic protocell
      cycle might be needed to guide future experiments. In this paper, we present a
      simple biochemically and physically feasible model of cell replication involving
      a discrete semi-permeable vesicle with an internal minimal metabolism involving
      two reactive centers. It is shown that such a system can effectively undergo a
      whole cell replication cycle. The model can be used as a basic framework to model
      whole protocell dynamics including more complex sets of reactions. The possible
      implementation of our design in future synthetic protocells is outlined.

PMID- 17184797
TI  - The shape of things to come: structural and synthetic studies of taxol and
      related compounds.
AB  - The history of the development of Taxol (paclitaxel) as an anticancer drug is
      reviewed, and some aspects of the phytochemistry of Taxus species and of the
      medicinal chemistry of taxol are discussed. The nature of the taxol-tubulin
      interaction is then described, with an emphasis on studies that led to the
      discovery and experimental proof of the T-taxol conformation as the tubulin
      binding conformation of taxol. The implications of this conformation for future
      drug development are also briefly covered.

PMID- 17184798
TI  - Protein kinase activity in Cucumis sativus cotyledons: effect of calcium and
      light.
AB  - Light signals received by phytochromes in plants may be transduced through
      protein phosphorylation. Ca(2+) as second messenger was involved in phytochrome
      mediated cellular events. Our experiments with Cucumis sativus cotyledons,
      treated with red (R) and far-red (FR) light, showed a stimulatory effect on in
      vitro protein phosphorylation of histone, added as exogenous substrate to the
      cotyledon extracts, and also modified the phosphorylation of endogenous
      polypeptides. The effect of light treatments was mimicked by the addition of
      Ca(2+) to the phosphorylation buffer, indicating phytochrome- and Ca(2+)
      dependence on activity of some protein kinases (PKs). In-gel kinase assays were
      performed to characterize the PKs involved at the cotyledon stage of cucumber
      plants. Three proteins of about 75, 57 and 47kDa with PK activity were detected
      between M(r) markers of 94 and 45kDa. All three were able to phosphorylate
      histone and undergo autophosphorylation. However, only the 75 and 57kDa proteins
      autophosphorylated and phosphorylated the substrate in a Ca(2+)-dependent manner,
      and were inhibited when calmodulin (CaM) antagonists were added to the incubation
      buffer. Western-blot analysis with polyclonal antibodies directed against calcium
      dependent protein kinase of rice (OsCDPK11) or Arabidopsis (AtCPK2) recognised 57
      and 75kDa polypeptides, respectively. These results indicate the presence in
      cucumber cotyledons of at least two proteins (ca. 75 and 57kDa) with activity of
      PKs that could be calcium-dependent protein kinases (CDPKs). Both CDPKs could be
      modulated by phytochromes throughout FR-HIR and VLFR responses.

PMID- 17184799
TI  - Plant progesterone 5beta-reductase is not homologous to the animal enzyme.
      Molecular evolutionary characterization of P5betaR from Digitalis purpurea.
AB  - Plants of the genus Digitalis produce cardiac glycosides, i.e. digoxin, which are
      widely used for congestive heart failure. Progesterone 5beta-reductase (P5betaR)
      is a key enzyme in the biosynthesis of these natural products. Here, we have
      carried out the purification and partial amino acid sequencing of the native
      P5betaR from foxglove (Digitalis purpurea), and isolated a cDNA encoding this
      enzyme. Similarly to other steroid 5beta-reductases, the recombinant P5betaR
      catalyzes the stereospecific reduction of the Delta(4)-double bond of several
      steroids with a 3-oxo,Delta(4,5) structure. The gene encoding P5betaR is
      expressed in all plant organs, and maximally transcribed in leaves and mature
      flowers. P5betaR belongs to the short-chain dehydrogenase/reductase (SDR)
      superfamily, bearing no structural homology to its mammalian counterpart, which
      is a member of the aldo-keto reductase (AKR) superfamily. A similar situation
      occurs with 3beta-hydroxy-Delta(5)-steroid dehydrogenase (3betaHSD), the gene
      immediately preceding P5betaR in the cardenolide pathway, which suggests that the
      entire route has evolved independently in animals and plants. P5betaR is retained
      only in plants, where it is ubiquitous, and a few distantly related bacterial
      lineages after its diversification from the last universal common ancestor.
      Evolutionary conserved changes in its putative active site suggest that plant
      P5betaR is a member of a novel subfamily of extended SDRs, or a new SDR family.

PMID- 17184800
TI  - Host/parasite relationship in the in vitro infection of rat gliocytes by Neospora
      caninum: evaluation of cell respiration.
AB  - Neospora caninum is a protozoon that causes abortion in cattle and neuromuscular
      lesions in dogs, with the formation of cysts mainly in the central nervous
      system. Since N. caninum is an intracellular parasite with tropism for the cells
      of nervous system, this study evaluated the respiratory metabolism of glial cells
      infected by this* parasite. Glial cultures obtained from the cerebral cortex of
      newborn rats were kept in DMEM enriched with 10% fetal bovine serum, 1 mM pyruvic
      acid and 2 mM of L-glutamine. They were infected at a ratio of approximately 1:1
      (cell/parasite). Oxygen consumption was evaluated by polarography in the non
      infected and N. caninum infected groups, 24 and 72 h following infection. Glial
      cell respiration after 24 and 72 h was 307.2 +/- 34.7 and 308.9 +/- 64.1 microL
      of oxygen per mug of total protein per minute, and 566.2 +/- 54.6 and 579 +/-
      117.5 microL O2/microg of total protein/minute in the control and infected
      groups, respectively. These results show that N. caninum does not interfere with
      glial respiration in vitro.

PMID- 17184801
TI  - Silymarin and epithelial cancer chemoprevention: how close we are to bedside?
AB  - Failure and high systemic toxicity of conventional cancer therapies have
      accelerated the focus on the search for newer agents, which could prevent and/or
      slow-down cancer growth and have more human acceptability by being less or non
      toxic. Silymarin is one such agent, which has been extensively used since ages
      for the treatment of liver conditions, and thus has possibly the greatest patient
      acceptability. In recent years, increasing body of evidence has underscored the
      cancer preventive efficacy of silymarin in both in vitro and in vivo animal
      models of various epithelial cancers. Apart from chemopreventive effects, other
      noteworthy aspects of silymarin and its active constituent silibinin in cancer
      treatment include their capability to potentiate the efficacy of known
      chemotherapeutic drugs, as an inhibitor of multidrug resistance-associated
      proteins and as an adjunct to the cancer therapeutic drugs due to their organ
      protective efficacy specifically liver, and immunostimulatory effects. Widespread
      use of silymarin for liver health in humans and commercial availability of its
      formulations with increased bioavailability, further underscore the necessity of
      carrying out controlled clinical trials with these agents in cancer patients. In
      this review, we will briefly discuss the outcomes of clinical trials being
      conducted by us and others in cancer patients to provide insight into the
      clinical relevance of the observed chemopreventive effects of these agents in
      various epithelial cancer models.

PMID- 17184802
TI  - Inhibition of viral replication reduces regulatory T cells and enhances the
      antiviral immune response in chronic hepatitis B.
AB  - Regulatory T cells (Treg) play a key role in the impaired immune response that is
      typical for a chronic Hepatitis B virus (HBV) infection. To gain more insight in
      the mechanism that is responsible for this impaired immune response, the effect
      of viral load reduction resulting from treatment with the nucleotide analogue
      adefovir dipivoxil on the percentages of Treg and HBV-specific T-cell responses
      was analyzed. Peripheral blood mononuclear cells (PBMC) of 12 patients were
      collected at baseline and during treatment. In parallel to the decline in viral
      load, we found a decline in circulating Treg, combined with an increase in HBV
      core antigen-specific IFN-gamma production and proliferation. The production of
      IL10 did not decrease during therapy. In conclusion, adefovir induced viral load
      reduction results in a decline of circulating Treg together with a partial
      recovery of the immune response.

PMID- 17184803
TI  - A conditionally replicating adenovirus with strict selectivity in killing cells
      expressing epidermal growth factor receptor.
AB  - Virotherapy of cancer using oncolytic adenoviruses has shown promise in both
      preclinical and clinical settings. One important challenge to reach the full
      therapeutic potential of oncolytic adenoviruses is accomplishing efficient
      infection of cancer cells and avoiding uptake by normal tissue through tropism
      modification. Towards this goal, we constructed and characterized an oncolytic
      adenovirus, carrying mutated capsid proteins to abolish the promiscuous
      adenovirus native tropism and encoding a bispecific adapter molecule to target
      the virus to the epidermal growth factor receptor (EGFR). The new virus displayed
      a highly selective targeting profile, with reduced infection of EGFR-negative
      cells and efficient killing of EGFR-positive cancer cells including primary EGFR
      positive osteosarcoma cells that are refractory to infection by conventional
      adenoviruses. Our method to modify adenovirus tropism might thus be useful to
      design new oncolytic adenoviruses for more effective treatment of cancer.

PMID- 17184804
TI  - Myxoma virus M063R is a host range gene essential for virus replication in rabbit
      cells.
AB  - The myxoma virus M063R gene product exhibits some sequence similarity to the
      poxvirus host range gene, C7L, of vaccinia virus. To address the potential host
      range function of the M063R gene product in rabbits, a deletion mutant of myxoma
      virus (vMyx63KO) was generated and characterized. vMyx63KO replicated to normal
      titre levels and produced foci that were indistinguishable from those produced by
      MV in vitro in a monkey kidney cell line (BGMK) that are permissive for wild type
      MV. However, vMyx63KO failed to replicate in all rabbit cell lines tested,
      including both primary and established cells lines, as well as cells derived from
      a variety of tissues. M063R expression was not required for myxoma virus binding,
      entry or early gene expression, whereas DNA replication was aborted and late
      genes were not expressed in vMyx63KO infected rabbit cells. Thus, the replication
      block for vMyx63KO in rabbit cells preceded the stage of late gene expression and
      DNA replication. Finally, an in vivo pathogenesis study indicated that vMyx63KO
      failed to cause any signs of classic myxomatosis in infected rabbits, but
      functioned as a non-replicating vaccine and provided protection for subsequent
      challenge by wild type myxoma virus. Altogether, these observations demonstrate
      that M063R plays a critical role in determining the host specificity of myxoma
      virus in rabbit cells.

PMID- 17184805
TI  - Stereo channels with different temporal frequency tunings.
AB  - To investigate the spatial and temporal frequency tunings for stereopsis, we
      measured the contrast sensitivity for depth discrimination with variable
      spatiotemporal frequencies and disparities using drifting sinusoidal gratings.
      The results showed that the contrast sensitivity changed with the stimulus
      disparity and the disparity tuning function varied with the spatial frequency.
      The disparity in the peak sensitivity decreased proportionally with the spatial
      frequency (size-disparity correlation). Although the temporal frequency exhibited
      a limited influence on the peak disparity, the temporal frequency tuning varied
      with the spatial frequency. The shape of the temporal frequency tuning function
      was lowpass for higher spatial frequencies, whereas it was bandpass for low
      spatial frequencies. These results suggest that more than one channel with
      different temporal as well as spatial frequency tunings contribute to stereopsis.

PMID- 17184806
TI  - The IOVP effect in mindless reading: experiment and modeling.
AB  - Fixation durations in reading are longer for within-word fixation positions close
      to word center than for positions near word boundaries. This counterintuitive
      result was termed the Inverted-Optimal Viewing Position (IOVP) effect. We
      proposed an explanation of the effect based on error-correction of mislocated
      fixations [Nuthmann, A., Engbert, R., & Kliegl, R. (2005). Mislocated fixations
      during reading and the inverted optimal viewing position effect. Vision Research,
      45, 2201-2217], that suggests that the IOVP effect is not related to word
      processing. Here we demonstrate the existence of an IOVP effect in "mindless
      reading", a z-string scanning task. We compare the results from experimental data
      with results obtained from computer simulations of a simple model of the IOVP
      effect and discuss alternative accounts. We conclude that oculomotor errors,
      which often induce mislocalized fixations, represent the most important source of
      the IOVP effect.

PMID- 17184808
TI  - The perceived position shift of a pattern that contains internal motion is
      accompanied by a change in the pattern's apparent size and shape.
AB  - When the sinusoidal grating of a "Gabor pattern" is drifted, the apparent
      position of the pattern shifts in the direction of motion [De Valois, R. L., & De
      Valois, K. K. (1991). Vernier acuity with stationary moving Gabors. Vision
      Research, 31, 1619-1626]. We investigated the underlying cause of this illusion
      by determining whether the effect is a consequence of the internal motion
      shifting the perceived position of the whole pattern, or a consequence of a shift
      in the perceived location of the centroid (centre of mass) of the Gabor envelope.
      While each of these two possible distortions can account for a perceived
      positional offset, they give different predictions for the apparent size of the
      stimulus. A simple shift in perceived position results in no change in apparent
      size, while a centroid shift will likely result in either a decrease or an
      increase in the pattern's apparent size, depending on whether the trailing or
      leading edge of the Gabor stimulus is most affected by motion. We examined
      whether there is a change in the apparent size of Gabor patterns containing a
      range of grating motion speeds. We found that the perceived size of the pattern
      increased in the presence of motion as a function of speed, and is thus
      consistent with a centroid-shift explanation. We verified that this size change
      is a consequence of an increase in contrast at the leading edge, since the
      leading edge appears elongated relative to the trailing edge. We furthermore
      showed that the apparent-position shifts due to motion can be negated by
      displacing the centroid in the opposite direction to the motion.

PMID- 17184807
TI  - Amblyopia in astigmatic children: patterns of deficits.
AB  - Neural changes that result from disruption of normal visual experience during
      development are termed amblyopia. To characterize visual deficits specific to
      astigmatism-related amblyopia, we compared best-corrected visual performance in
      330 astigmatic and 475 non-astigmatic kindergarten through 6th grade children.
      Astigmatism was associated with deficits in letter, grating and vernier acuity,
      high and middle spatial frequency contrast sensitivity, and stereoacuity.
      Although grating acuity, vernier acuity, and contrast sensitivity were reduced
      across stimulus orientation, astigmats demonstrated orientation-dependent
      deficits (meridional amblyopia) only for grating acuity. Astigmatic children are
      at risk for deficits across a range of visual functions.

PMID- 17184809
TI  - Dopaminergic modulation and rod contribution in the generation of oscillatory
      potentials in the tiger salamander retina.
AB  - The roles of rod and cone input and of dopamine in the generation of oscillatory
      potentials were studied in tiger salamander retina. Under scotopic conditions,
      oscillations were elicited with a green, but not a red stimulus. With mesopic
      background illumination, both stimuli caused oscillations. Addition of quinpirole
      to a mesopic retina eliminated oscillations while SKF-38393 had no effect.
      Similarly, addition of sulpiride to a light-adapted retina elicited oscillatory
      activity, but SCH 22390 had no effect. These results suggest that oscillatory
      potentials are elicited through activation of the rod pathway and are modulated
      by dopamine through D2-receptors.

PMID- 17184810
TI  - Bacterial community structures in MBRs treating municipal wastewater:
      relationship between community stability and reactor performance.
AB  - Bacterial community structures in pilot-scale conventional membrane bioreactors
      (CMBRs) and hybrid MBRs (HMBRs) which were combined with pre
      coagulation/sedimentation were analyzed by polymerase chain reaction-denaturing
      gradient gel electrophoresis (PCR-DGGE) and fluorescence in situ hybridization
      (FISH) techniques. The results were compared with the community structure in a
      full-scale activated sludge (AS) process treating the same municipal wastewater.
      The Dice index (Cs) of similarity analysis of DGGE banding patterns demonstrated
      that the microbial community in AS was more similar to those in CMBR1 and CMBR2
      than HMBR1 and HMBR2. This suggested that influent wastewater composition had a
      larger impact on bacterial community structures. Long-term community structure
      changes in the HMBRs and CMBRs were monitored and analyzed over 240 days by Non
      metric multidimensional scaling (NMDS) analysis of DGGE banding patterns. The
      NMDS analysis revealed that both HMBRs and CMBRs had marked changes in community
      structures during the first about 100 days. Thereafter the perpetual fluctuations
      of bacterial community structures were observed in both HMBRs and CMBRs, even
      though the stable MBR performances (the performance was measured as membrane
      permeability and removal of dissolved organic carbon, DOC) were achieved. These
      results suggest that not only the stability, but also the adequate dynamics
      ("flexibility") of the bacterial community structure are important for the stable
      performance of the MBRs treating complex municipal wastewater.

PMID- 17184811
TI  - Spectrofluorometric properties of dissolved organic matter from Central and
      Southern Ontario streams and the influence of iron and irradiation.
AB  - Fluorescence measurements were used to compare characteristics of dissolved
      organic matter (DOM) from distinctly different origins: boreal, agricultural and
      urban streams as well as a storm runoff pond and the outlet of a tertiary
      wastewater treatment plant. The primary goal was to determine if differences
      among stream types could be detected using DOM fluorescence in lieu of isolated
      fulvic acids (FA). Differences in peak excitation and peak emission wavelengths,
      fluorescence integrated over the 3-D matrix volume integrated fluorescence (VIF),
      and in a fluorescence index (FI) were examined. In general, peak fluorescence
      excitation and emission wavelengths as well as FI best distinguished DOM from the
      various origins. Results suggested that DOM from the boreal streams was of a
      higher molecular weight and more complex than that of agricultural and urban
      streams. The effects of irradiation as well as Fe on fluorescence of natural
      stream waters were also investigated, both of which decreased the ability of
      optical properties to distinguish DOM source.

PMID- 17184812
TI  - Dynamics of drinking water biofilm in flow/non-flow conditions.
AB  - Drinking water biofilm formation on polyvinyl chloride (PVC), cross-linked
      polyethylene (PEX), high density polyethylene (HDPE) and polypropylene (PP) was
      followed in three different reactors operating under stagnant or continuous flow
      regimes. After one week, a quasi-steady state was achieved where biofilm total
      cell numbers per unit surface area were not affected by fluctuations in the
      concentration of suspended cells. Metabolically active cells in biofilms were
      around 17-35% of the total cells and 6-18% were able to form colony units in
      R(2)A medium. Microbiological analysis showed that the adhesion material and
      reactor design did not affect significantly the biofilm growth. However,
      operating under continuous flow (0.8-1.9 Pa) or stagnant water had a significant
      effect on biofilm formation: in stagnant waters, biofilm grew to a less extent.
      By applying mass balances and an asymptotic biofilm formation model to data from
      biofilms grown on PVC and HDPE surfaces under turbulent flow, specific growth
      rates of bacteria in the biofilm were found to be similar for both materials
      (around 0.15 day(-1)) and much lower than the specific growth rates of suspended
      bacteria (around 1.8 day(-1)).

PMID- 17184813
TI  - Oxidative degradation of N-nitrosodimethylamine by conventional ozonation and the
      advanced oxidation process ozone/hydrogen peroxide.
AB  - This study investigates the oxidative degradation of N-nitrosodimethylamine
      (NDMA), a probable human carcinogen, by conventional ozonation and the advanced
      oxidation process ozone/hydrogen peroxide (AOP O(3)/H(2)O(2)). The rate constants
      of reactions of NDMA with ozone and hydroxyl radical ((*)OH) were determined to
      be 0.052+/-0.0016M(-1)s(-1) and (4.5+/-0.21)x10(8)M(-1)s(-1), respectively. The
      experiments performed with buffered deionized water varying solution pH and
      employing H(2)O(2) and HCO(3)(-) clearly showed that the reaction with (*)OH
      dominates the NDMA oxidation during ozonation. Conventional ozonation with up to
      160 microM (=7.7 mgL(-1)) ozone led to less than 25% NDMA oxidation in natural
      waters. The AOP O(3)/H(2)O(2) required 160-320 microM ozone
      ([O(3)](0)/[H(2)O(2)](0)=2:1) to achieve 50-75% NDMA oxidation. However, multiple
      injections of ozone of the same overall dose somewhat improved the oxidant
      utilization efficiency by minimizing (*)OH scavenging contribution of oxidants.
      Methylamine (MA) was found to be a major amino product from NDMA oxidation
      initiated by (*)OH. The mechanism of NDMA oxidation to MA is discussed based on
      the results obtained in this study and the previous literature. Bromate formation
      may be the limiting factor for NDMA oxidation during ozonation and ozone-based
      AOPs in bromide-containing waters.

PMID- 17184814
TI  - The use of maize and poplar in chelant-enhanced phytoextraction of lead from
      contaminated agricultural soils.
AB  - Chelant-enhanced phytoextraction of heavy metals is an emerging technological
      approach for a non-destructive remediation of contaminated soils. The main
      objectives of this study were (i) to assess the extraction efficiency of two
      different synthetic chelating agents (ethylenediaminetetraacetic acid (EDTA) and
      ethylenediaminedisuccinic acid (EDDS)) for desorbing Pb from two contaminated
      agricultural soils originating from a mining and smelting district and (ii) to
      assess the phytoextraction efficiency of maize (Zea mays) and poplar (Populus
      sp.) after EDTA application. EDTA was more efficient than EDDS in desorbing and
      complexing Pb from both soils, removing as much as 60% of Pb. Maize exhibited
      better results than poplar when extracting Pb from the more acidic (pH
      approximately 4) and more contaminated (up to 1360 mg Pb kg(-1)) agricultural
      soil originating from the smelting area. On the other hand, poplars proved to be
      more efficient when grown on the near-neutral (pH approximately 6) and less
      contaminated (up to 200 mg Pb kg(-1)) agricultural soil originating from the
      mining area. Furthermore, the addition of EDTA led to a significant increase of
      Pb content especially in poplar leaves, proving a strong translocation rate
      within the poplar plants.

PMID- 17184816
TI  - Determination of commonly used polar herbicides in agricultural drainage waters
      in Australia by HPLC.
AB  - The present study describes the application of different extraction techniques
      for the preconcentration of ten commonly found acidic and non-acidic polar
      herbicides (2,4-D, atrazine, bensulfuron-methyl, clomazone, dicamba, diuron,
      MCPA, metolachlor, simazine and triclopyr) in the aqueous environment. Liquid
      liquid extraction (LLE) with dichloromethane, solid-phase extraction (SPE) using
      Oasis HLB cartridges or SBD-XC Empore disks were compared for extraction
      efficiency of these herbicides in different matrices, especially water samples
      from contaminated agricultural drainage water containing high concentrations of
      particulate matter. Herbicides were separated and quantified by high performance
      liquid chromatography (HPLC) with an ultraviolet detector. SPE using SDB-XC
      Empore disks was applied to determine target herbicides in the Murrumbidgee
      Irrigation Area (NSW, Australia) during a two-week survey from October 2005 to
      November 2005. The daily aqueous concentrations of herbicides from 24-h composite
      samples detected at two sites increased after run-off from a storm event and were
      in the range of: 0.1-17.8 microg l(-1), < 0.1-0.9 microg l(-1) and 0.2-17.8
      microg l(-1) at site 1; < 0.1-3.5 microg l(-1), < 0.1-0.2 microg l(-1) and < 0.2
      3.2 microg l(-1) at site 2 for simazine, atrazine and diuron, respectively.

PMID- 17184815
TI  - Fungal biofilters for toluene biofiltration: evaluation of the performance with
      four packing materials under different operating conditions.
AB  - Packing materials play a key role in the performance of bioreactors for waste gas
      treatment and particularly in biofilter applications. In this work, the
      performance of four differently packed biofilters operated in parallel for the
      treatment of relatively high inlet concentration of toluene was studied. The
      reactors were compared for determining the suitability of coconut fiber, digested
      sludge compost from a waste water treatment plant, peat and pine leaves as
      packing materials for biofiltration of toluene. A deep characterisation of
      materials was carried out. Biological activity and packing capabilities related
      to toluene removal were determined throughout 240 days of operation under
      different conditions of nutrients addition and watering regime. Also, biofilters
      recovering after a short shutdown was investigated. Nutrient addition resulted in
      improved removal efficiencies (RE) and elimination capacities (EC) of biofilters
      reaching maximum ECs between 75 and 95 g m(-3)h(-1) of toluene. In the first 80
      days, the pH decreased progressively within the reactors, causing a population
      change from bacteria to fungi, which were the predominant decontaminant
      microorganisms thereafter. All reactors were found to recover the RE rapidly
      after a 5 days shutdown and, in a maximum of 7 days, all reactors had been
      completely recuperated. These results point out that fungal biofilters are a
      suitable choice to treat high loads of toluene. In general, coconut fiber and
      compost biofilters exhibited a better performance in terms of elimination
      capacity and long-term stability.

PMID- 17184817
TI  - Bacillus thuringiensis fermentation of hydrolyzed sludge--rheology and
      formulation studies.
AB  - Rheology of Bacillus thuringiensis fermentation of hydrolyzed sludge was
      investigated in bench scale fermenter. Stable liquid formulations were developed
      and optimized for two-year based studies comprising various physical/chemical
      (viscosity, particle size, corrosion and suspendibility) and biological
      (microbial contamination, viable spores and entomotoxicity) parameters at
      different pHs and temperatures. The hydrolyzed sludge depicted non-Newtonian and
      pseudoplastic behaviour during fermentation with 90% to 96% confidence of fits
      into Casson, Power and IPC paste models. Higher values of consistency and flow
      index during exponential growth and stationary phase, respectively, affected
      downstream processing. The power law was also followed by stable formulations.
      Sorbitol, sodium monophosphate and sodium metabisulfite (2.2:1:1) as suspending
      agents produced suspendibility ranging from 69% to 94%. The stable formulation
      (FH-4) comprising sorbitol, sodium monophosphate and sodium metabisulfite
      deteriorated at pHs 6, 6.5 and temperatures, 40 and 50 degrees C, with no signs
      of corrosion and microbial contamination. The viscosity of FH-4 formulations
      decreased with shear rate which could improve handling and consequent spraying.

PMID- 17184818
TI  - Effect of the herbicide flumioxazin on photosynthetic performance of grapevine
      (Vitis vinifera L.).
AB  - Among the herbicides used in vineyards, the pre-emergence soil-applied
      flumioxazin (fmx) is a recently used molecule that inhibits chlorophyll
      biosynthesis in weed species. The aim of this work is to further characterize the
      effects of fmx on the non-target grapevine (Vitis vinifera L. cv. Chardonnay)
      using cutting as a model. Several photosynthesis parameters were estimated during
      25 days after treatment with various fmx concentrations (from 0.5mM to 50mM).
      Measuring chlorophyll fluorescence it appeared that fmx or a by-product
      penetrated the plant throughout roots and spread throughout vessels. Besides the
      initial target, protox, fmx affected other functions related to photosynthesis.
      Fmx induced a simultaneous drop of both P(n), g(s) and T. Fmx caused stomatal
      closure, which partially explains the decrease of the net photosynthesis. The
      decline in F(v)/F(m) indicates that the photochemistry of PSII and its ability to
      reduce the primary acceptor Q(A) are also affected by fmx in grapevine. Fmx leads
      to a decrease in the coefficients of both photochemical and non-photochemical
      quenching. Simultaneous stomatal closure and decrease in the quantum yield of
      CO(2) assimilation indicate a change in energy metabolism following fmx stress.
      After ten days of fmx treatment, analyses of the response of net carbon
      assimilation in leaves to different intercellular CO(2) concentrations have shown
      a decrease of the maximum carboxylation velocity of RuBP. Stomatal closure, PSII
      photochemistry, change in energy metabolism and RuBP activity were affected by
      fmx treatment.

PMID- 17184819
TI  - Effects of NO2 and SO2 on selective catalytic reduction of nitrogen oxides by
      ammonia.
AB  - The selective catalytic reduction (SCR) characteristics of NO and NO(2) over
      V(2)O(5)-WO(3)-MnO(2)/TiO(2) catalyst using ammonia as a reducing agent have been
      determined in a fixed-bed reactor at 200-400 degrees C. The presence of NO(2)
      enhances the SCR activity at lower temperatures and the optimum ratio of
      NO(2)/NO(x) is found to be 0.5. During the SCR reactions, there are some side
      reactions occurred such as ammonia oxidation and N(2)O formation. At higher
      temperatures, the selective catalytic oxidation of ammonia and the nitrous oxide
      formation compete with the SCR reactions. The denitrification (DeNO(x))
      conversion decreases at lower temperatures but it increases at higher
      temperatures with increasing SO(2) concentration. The presence of SO(2) in the
      feeds inhibits N(2)O formation.

PMID- 17184820
TI  - QSARs for the toxicity of polychlorinated dibenzofurans through DFT-calculated
      descriptors of polarizabilities, hyperpolarizabilities and hyper-order electric
      moments.
AB  - DFT-B3LYP method with 6-31G(**) basis set was employed to fully optimize the
      electronic structures of 135 polychlorinated dibenzofurans and parent compound,
      namely dibenzofuran. It was demonstrated that polarizability anisotropy and mean
      polarizability could change sensitively and systematically with chlorine number
      and substitution pattern. And new quantitative structure-activity relationships
      (QSARs) focused on the binding affinities of aryl hydrocarbon receptor (AhR),
      aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (EROD)
      induction potencies of PCDFs were developed. It was concluded that polarizability
      anisotropy in conjunction with hyperpolarizabilties and hyper-order electric
      moments, e.g. octupole moments could well interpret the variation of toxicity of
      different congeners and dispersion interaction should be the leading form among
      various interactions. Although the terms of hyperpolarizabilities and hyper-order
      electric moments were not the same significant ones as polarizability anisotropy,
      the long-range interactions characterized by them should not be ignored in
      explaining the toxicity.

PMID- 17184821
TI  - Impact assessment of cadmium contamination on rice (Oryza sativa L.) seedlings at
      molecular and population levels using multiple biomarkers.
AB  - Assessment of environmental contamination on ecology (plant) at molecular and
      population levels is important in risk quantification and remediation study.
      Random amplified polymorphic DNA (RAPD) assay and related other fingerprinting
      techniques have been employed to detect the genotoxin-induced DNA damage and
      mutations. This research compared the effects occurring at molecular and
      population levels in rice seedlings exposed to cadmium (Cd) concentrations of 15
      60 mg l(-1) for 8 days with quartz sand culture. Inhibition of root growth and
      increase of total soluble protein content in root tips of rice seedlings were
      observed with the increase of Cd concentration. For the RAPD analyses, 12 RAPD
      primers of 50-70% GC content were found to produce unique polymorphic band
      patterns and subsequently were used to produce a total of 180 bands of 179-3056
      bp in molecular size in the control root tips of rice seedlings. Results produced
      by these RAPD primers indicate that changes in RAPD profiles of root tips after
      Cd treatment include modifications in band intensity and gain or loss of bands by
      comparison with control. The effect of changes was dose-dependent. Genomic
      template stability compares favourably with the traditional indices such as root
      growth and soluble protein content. The DNA polymorphisms detected by RAPD
      analysis can be applied as a suitable biomarker assay for the detection of
      genotoxic effects of Cd contamination on plants.

PMID- 17184822
TI  - Computer-based QSARs for predicting mixture toxicity of benzene and its
      derivatives.
AB  - During the past decades, the Quantitative structure-activity relationships
      (QSARs) have been proven to be reliable tools when little or no empirical data
      are available in medicinal chemistry, biochemistry, toxicology, and environmental
      sciences. However, only few studies that quantitatively predict mixtures toxicity
      have been reported. In this study, the QASR models for the binary mixtures
      toxicity of 12 benzene and its derivatives, including eight non-polar-narcotic
      compounds and four polar narcotic compounds were developed, without reference to
      exact toxicity mechanisms of single compounds. All parameters for the QSAR
      studies were defined on the basis of quantum mechanical calculations and these
      parameters were selected by the stepwise procedure. The results of this study
      provided a simple means of predicting the binary mixtures toxicity from the
      chemical structure.

PMID- 17184823
TI  - Evolution of heavy metal speciation during the aerobic composting process of
      sewage sludge.
AB  - The contents of heavy metals and their bioavailability to the soil-plant system
      were the major limitation to the application of sewage sludge compost in soil.
      This study was conducted to determine the evolution of heavy metal speciation in
      the course of an aerobic composting, and investigate the influence of changes of
      composting process parameters including pH, temperature and organic matter (OM)
      content on distribution of heavy metal speciation in composted sludge. The
      sequential extraction procedure developed by Tessier et al. was used in sludge
      compost to determine the heavy metal speciation. Results showed that, during
      composting, (1) the contents of the residue fraction for Pb, Zn and Cd were
      decreased but those for Ni and Cr were increased; the Cu residue fraction was
      almost constant; (2) the contents of the total mobile fractions (including
      fractions 1-4) for Zn and Pb were significantly increased, but the increase of
      those for Cu and Ni were not so remarkable; (3) there were significant degrees of
      correlation between heavy metal fractions and changes of some selected parameters
      (for example, pH, composting temperature, and OM content). Only the content of
      the total mobile fractions for Cu could be predictable from its total content.
      For the prediction of the total mobile fractions of Zn, Ni, Cd and Cr, the R(2)
      value was significantly increased by the inclusion of other variables such as pH,
      temperature and OM content.

PMID- 17184824
TI  - The source of naturally occurring arsenic in a coastal sand aquifer of eastern
      Australia.
AB  - The discovery of dissolved arsenic in a coastal aquifer used extensively for
      human consumption has led to widespread concern for its potential occurrence in
      other sandy coastal environments in eastern Australia. The development of an
      aquifer specific geomorphic model (herein) suggests that arsenic is regionally
      derived from erosion of arsenic-rich stibnite (Sb(2)S(3)) mineralisation present
      in the hinterland. Fluvial processes have transported the eroded material over
      time to deposit an aquifer lithology elevated in arsenic. Minor arsenic
      contribution to groundwater is derived from mineralised bedrock below the
      unconsolidated aquifer. An association with arsenic and pyrite has been observed
      in the aquifer in small discrete arsenian pyrite clusters rather than actual acid
      sulfate soil horizons. This association is likely to influence arsenic
      distribution in the aquifer, but is not the dominant control on arsenic
      occurrence. Arsenic association with marine clays is considered a function of
      their increased adsorptive capacity for arsenic and not solely on the influence
      of sea level inundation of the aquifer sediments during the Quaternary Period.
      These findings have implications for, but are not limited to, coastal aquifers.
      Rather, any aquifer containing sediments derived from mineralised provenances may
      be at risk of natural arsenic contamination. Groundwater resource surveys should
      thus incorporate a review of the aquifer source provenance when assessing the
      likely risk of natural arsenic occurrence in an aquifer.

PMID- 17184825
TI  - Association between estrogen receptor alpha and beta gene polymorphisms and deep
      vein thrombosis.
AB  - BACKGROUND: Estrogen and the estrogen receptors alpha (ESR1) and beta (ESR2) play
      a role in regulating genes, including coagulation and fibrinolysis genes.
      OBJECTIVE: We investigated the association between ESR1 c.454-397T>C and c.454
      351A>G and ESR2 1082A>G and 1730A>G polymorphisms and the risk of deep vein
      thrombosis (DVT), in 134 patients and 134 controls with acquired risk factors for
      thrombosis associated with estrogen alterations, such as pregnancy, puerperium,
      oral contraceptives (OC), and hormone replacement therapy (HRT). We also analysed
      134 men with DVT. We investigated the relationship of these polymorphisms and the
      levels of fibrinogen, protein C (PC), protein S (PS), and antithrombin (AT)
      activity. METHODS: Gene polymorphisms were identified by using PCR and RFLP.
      Coagulation methods were used to measure PC, PS, and fibrinogen. Chromogenic
      methods were used to quantify AT. RESULTS AND CONCLUSIONS: The presence of the AA
      genotype of the 1730G>A polymorphism (OR=0.18; 95%CI=0.05-0.62) suggests a
      protective effect for DVT in women using OC. As the GG genotype of the 1730G>A
      polymorphism is associated with increased PS activity in all control women and
      women using OC, this suggested that a protective effect must occur by another
      pathway not related to PS. The AA and AG genotypes of the c.454-351A>G and GG
      genotype of the 1082G>A polymorphisms are associated with increased fibrinogen
      concentration in pregnant women. The GG haplotype in the ESR2 gene (P<0.001) was
      related to factor V Leiden or G20210A mutation in the prothrombin gene, or both,
      as predictive factors of DVT.

PMID- 17184826
TI  - Non-genital tract metastases to the ovaries presented as ovarian tumors in Sweden
      1990-2003: occurrence, origin and survival compared to ovarian cancer.
AB  - OBJECTIVE: The aim of this register study was to determine occurrence of non
      genital ovarian metastasis detected by gynecologic surgery presented as ovarian
      neoplasm in Sweden from 1 January 1990 to 31 December 2003. Origin of metastases
      and time of detection in relation to surgery were recorded. Age at diagnosis,
      survival for ovarian metastasis compared to ovarian cancer and prognostic factors
      were evaluated. METHODS: Utilizing the population-based Swedish In-Patient
      Registry, Cancer Registry and Causes of Death Registry, we identified 255 cases
      with non-genital tract metastases to the ovaries detected at gynecological
      surgery. During the study period, 10,955 newly diagnosed cases of ovarian cancer
      were reported to the Swedish Cancer Registry. RESULTS: The proportion of ovarian
      metastases detected at surgery of all ovarian neoplasm increased from 1.7% to
      3.0% during the study period. The patients with ovarian metastasis of non-GI
      origin were younger than patients with primary ovarian cancer. The most common
      primary diseases were breast cancer (29%), colon cancer (27%) and gastric cancer
      (16%). Ovarian metastasis of GI origin preceded primary diagnosis in 51% of
      patients but for women with disease of non-GI origin the primary diagnosis was
      made in 18% of patients after surgery. Five-year survival for patients with
      ovarian metastasis of GI origin was 11% and it was 24% if metastases were of non
      GI origin. Five-year survival for women with ovarian metastases from breast
      cancer was 26%. In a multivariate analysis, GI surgery at primary surgery for
      ovarian metastasis was unfavorable prognostic factor. Diagnosis of primary
      disease known before surgery, primary disease of non-GI or unknown origin and
      operation at university hospital all had favorable prognostic impact for overall
      survival. CONCLUSIONS: Detection of non-genital ovarian metastasis at gynecologic
      surgery is associated with poor prognosis, and prognosis is worse in tumors with
      GI origin and if the primary is not detected prior to surgery. The results
      indicate that a thorough patient evaluation is very important before surgery for
      suspected ovarian neoplasm.

PMID- 17184827
TI  - Effects of dextromethorphan on rats' acquisition of responding with delayed
      reinforcement.
AB  - Separate groups of 16 rats received 0, 40, 60, or 80 mg/kg dextromethorphan prior
      to a 2-h response-acquisition session during which responses on one lever
      produced food (reinforcement lever, RL, responses) after a 15-s resetting delay
      and responses on the other lever cancelled food deliveries earned by RL
      responses, but otherwise had no programmed consequences. When compared to the 0
      mg/kg dose, the 40, 60, and 80 mg/kg doses significantly decreased the latency to
      the tenth RL response, which has been used previously as an index of response
      acquisition [Pallares, MA, Nadal, RA, Silvestro, JS, Ferre, NS. Effects of
      ketamine, a noncompetitive NMDA antagonist, on the acquisition of the lever-press
      response in rats. Physio Behav 1995; 57:389-392.]. Only the 80 mg/kg dose,
      however, significantly reduced the total number of food pellets earned, the total
      number of RL responses, or the total number of rats that met the criterion for
      response acquisition. The present results indicate that dextromethorphan can
      disrupt initial response acquisition (i.e., learning) with positive
      reinforcement, although the dose that did so depended on the measure used to
      index performance. Moreover, the effects of the drug did not appear to reflect
      specific learning impairment, but rather more general disruption of behavior.

PMID- 17184828
TI  - Older persons afraid of falling reduce physical activity to prevent outdoor
      falls.
AB  - OBJECTIVE: The aim of this study was to test the assumption that the level of
      outdoor physical activity mediates the relationship between fear of falling and
      actual outdoor falls according to the Task Difficulty Homeostasis Theory. METHOD:
      A prospective follow-up study of 10 months conducted in the year 2000 in three
      municipalities in the province of Friesland, The Netherlands. The participants
      were 1752 people aged 65 and older, living independently, in the community. Main
      baseline data were age, sex, outdoor physical activities (walking, bicycling),
      and fear of outdoor falls. The number of people who fell outdoors was recorded.
      RESULTS: People with a high fear of falling were more often low to moderately
      active or active compared with people who had no such fears and were more often
      very active. Fear of falling was not associated with outdoor falls, but it was
      after taking the level of physical activity into account. CONCLUSIONS: Outdoor
      physical activity mediates the relationship between fear of falling and actual
      outdoor falls. This implies that the incidence of falls as an outcome in studies
      does not adequately represent the impact of risk factors for falls and that level
      of physical activity should be taken into account.

PMID- 17184829
TI  - Does the periodic vegetarianism of Greek Orthodox Christians benefit blood
      pressure?
AB  - OBJECTIVE: The Greek Orthodox Christian (GOC) diet is a periodic vegetarian-type
      diet that shares all the characteristics of the Mediterranean diet. No study to
      date has investigated its impact on blood pressure (BP). METHODS: Thirty-eight
      devout Orthodox Christian fasters and 29 matched controls living in Crete,
      Greece, were followed for 1 year during 2001. BP data were gathered before (pre)
      and near completion (end) of the three major fasting periods of the Orthodox
      Christian calendar [Christmas (40 days)-Easter (48 days)-Assumption (15 days)]
      along with other information on their dietary and lifestyle habits, body
      measurements and blood samples. RESULTS: Throughout the study fasters had higher
      mean SBP and DBP than controls. No fasting period had a significant BP lowering
      effect on fasters. Fasters' prevalence of end-Christmas and end-Lent high-normal
      BP was significantly higher than that of the controls', while it was reduced
      during the Assumption and reached the very low levels of controls'. On the whole,
      compared to controls, fasters increased their fiber, magnesium and fruit and
      vegetable consumption during the fasting periods and decreased their sodium and
      calcium intake. BMI and blood lipids were significantly associated with SBP/DBP
      at almost all measurements. CONCLUSION: Religious adherence to a periodic
      vegetarian Mediterranean-style diet does not have an observable effect on BP.
      Further research is needed in order to establish conclusive evidence.

PMID- 17184830
TI  - The effect of a primary care exercise intervention for rural women.
AB  - OBJECTIVE: Rural women have limited exercise opportunities and significant
      barriers to engaging in physical activity. This study assessed the effect of a
      brief primary care based walking intervention in rural women. METHODS: The
      participants were recruited in March, 2003 by a primary care nurse at three
      locations in rural Missouri. The enrolled subjects were given a pedometer,
      exercise videotape and provided exercise counseling at intake and four time
      points over 6 months. The week 1 pedometer step counts were compared with step
      counts at 6-month follow-up. RESULTS: Of the initial 75 participants, 61
      completed at least one follow up encounter. The participant's mean age was 42.5
      years. At intake, the majority of women (90%) exhibited one or more risk factors
      for cardiovascular disease; 78% were obese or overweight. Although most (62%)
      women reported being physically active, the mean pedometer reading was low at
      6337 steps per day at week 1. Over the follow-up period, participants increased
      their step counts by a mean of 2573 steps per day (p<.001). Increases in step
      counts were seen in normal weight, overweight and obese participants.
      CONCLUSIONS: A simple walking intervention through a primary care practice was
      effective in increasing the short term walking rates of rural women.

PMID- 17184831
TI  - Incidence and risk factors of disability in the elderly: the Rotterdam Study.
AB  - BACKGROUND: This study analyzed the incidence of disability and its risk factors
      in multiple dimensions in community-dwelling women and men of older age, between
      1990 and 1999, in Rotterdam, The Netherlands. METHODS: For this community-based
      prospective longitudinal study, data were obtained from the Rotterdam Study that
      comprised a cohort of 7983 elderly who are 55 and over. The study sample for
      incident disability consisted of 4258 subjects who were disability free at
      baseline and had complete outcome data at follow-up, 6 years later.
      Sociodemographic factors, lifestyle variables, health conditions and disability
      status were assessed at baseline and follow-up. Disability was defined as a
      Disability Index (DI) > or =0.50 according to the Health Assessment
      Questionnaire. RESULTS: Multivariate analyses, performed separately due to gender
      differences, revealed that age, self-rated health, overweight, depression, joint
      complaints, medication use were predictors of disability for both men and women.
      Stroke, falling and presence of comorbidities predicted disability in men only
      while having a partner, poor cognitive functioning, osteoarthritis and morning
      stiffness only predicted disability in women. CONCLUSION: Identified risk factors
      in this study are to some extent modifiable, enabling interventive strategies,
      reckoning with gender differences in risk profile, in order to prevent
      disability.

PMID- 17184832
TI  - Corrosion by galvanic coupling between amalgam and different chromium-based
      alloys.
AB  - OBJECTIVES: In recent years there has been an increase in the use of dental
      casting alloys in prosthodontic treatment. Many patients have metals or alloys,
      as well as amalgam fillings, in their mouth, and will have them for many years.
      The aim of this study was to evaluate and compare, in vitro, the galvanic
      corrosion behavior of chromium-cobalt alloy (Remanium GM 380) and chromium-nickel
      alloy (Remanium CS) when bound together or coupled with silver-based amalgam
      (Amalcap plus). METHODS: An electrochemical characterization of the alloys was
      performed by potentiostatic and potentiodynamic methods, i.e. the open circuit
      potential (OCP), the corrosion potential (E(CORR)), corrosion current density
      (i(CORR)) and corrosion resistance (R(P)). The electromotive force (EMF) of the
      bimetallic cells was also tested. Electroanalytical techniques were used to
      estimate the release of any respective element from the dental alloys under study
      into the artificial saliva solution. RESULTS: It was found that a bimetallic cell
      consisting of Remanium CS and Remanium GM 380 alloys has a very low EMF (a few
      mV) and is not a potential source of galvanic currents in the oral cavity.
      However, galvanic cells prepared from Amalcap plus and Remanium CS or Remanium GM
      380 showed a much greater EMF: 104 and 109mV, respectively. This clearly
      indicates that in these latter cases it is possible to expect some metal ions in
      the saliva solution as a result of the work of galvanic currents. It was found,
      by adsorptive stripping voltammetry analysis, that nickel or cobalt, depending on
      the alloy used, appeared in the saliva solution and increased in concentration
      over time. SIGNIFICANCE: The results indicate that the correct design and use of
      dental alloys are important when determining the appropriate treatment for a
      specific patient.

PMID- 17184833
TI  - Failure mode of dental restorative materials under Hertzian indentation.
AB  - OBJECTIVE: To explore the application of Hertzian indentation testing to amalgam
      and GIC; study the failure behavior of the bi-layer structure of each material on
      a relatively soft substrate; and investigate the effect of thickness. METHODS:
      Amalgam (Lojic+, SDI, Bayswater, Australia) and ceramic-reinforced GIC (Advanced
      Healthcare, Tonbridge, UK) discs, 10 mm diameter, thicknesses ranging from 0.4 to
      8.0 mm, were tested resting freely on a substrate (30% glass fibre-reinforced
      polyamide; E=10GPa, 10 mm diameter and 5 mm thick). Increasing load was applied
      to the center of the disc by a 20 mm-diameter hard steel ball until fracture
      occurred. Acoustic emission sensing was used as a supplemental method for crack
      detection. The load at the first crack was recorded. Fracture surfaces were
      observed under SEM to identify the crack initiation site and the failure mode.
      RESULTS: The main failure mode of both materials shifted from bottom-initiated
      radial cracking to near-contact cone cracking or subsurface plastic deformation
      as the thickness was increased. There was a wide thickness range for the
      transition of the failure mode for amalgam. Failure load was proportional to the
      square of thickness for amalgam, except for deviations at small and very large
      thickness; for the GIC, it was proportional to the thickness to the power
      approximately 1.6, except for thin layers. SIGNIFICANCE: The Hertzian indentation
      test can be applied to investigate the failure behavior of amalgam and GIC in
      addition to ceramics, for which purpose it may have value as a routine test.
      Failure mode changed with specimen thickness. The importance of considering both
      failure mode and failure load or strength is emphasized.

PMID- 17184834
TI  - Retinol and retinoic acid bind human serum albumin: stability and structural
      features.
AB  - Vitamin A components, retinol and retinoic acid, are fat-soluble micronutrients
      and critical for many biological processes, including vision, reproduction,
      growth, and regulation of cell proliferation and differentiation. The cellular
      uptake of Vitamin A is through specific interaction of a plasma membrane receptor
      with serum retinol-binding protein. Human serum albumin (HSA), as a transport
      protein, is the major target of several micronutrients in vivo. The aim of
      present study was to examine the interaction of retinol and retinoic acid with
      human serum albumin in aqueous solution at physiological conditions using
      constant protein concentration and various retinoid contents. FTIR, UV-vis, CD
      and fluorescence spectroscopic methods were used to determine retinoid binding
      mode, the binding constant and the effects of complexation on protein secondary
      structure. Structural analysis showed that retinol and retinoic acid bind non
      specifically (H-bonding) via protein polar groups with binding constants of
      K(ret)=1.32 (+/-0.30)x10(5)M(-1) and K(retac)=3.33 (+/-0.35)x10(5)M(-1). The
      protein secondary structure showed no alterations at low retinoid concentrations
      (0.125 mM), whereas at high retinoid content (1mM), an increase of alpha-helix
      from 55% (free HSA) to 60% and a decrease of beta-sheet from 22% (free HSA) to
      18% occurred in the retinoid-HSA complexes. The results point to a partial
      stabilization of protein secondary structure at high retinoid content.

PMID- 17184835
TI  - Controlled release of vancomycin from thin sol-gel films on titanium alloy
      fracture plate material.
AB  - Risk of infection is considerable in open fractures and its management is
      challenging, especially when fracture fixation material is used. Thus, it may be
      desirable to use a device from which antibiotics can be released in a controlled
      way. Room temperature processed silica sol-gels are novel, resorbable and
      biocompatible, controlled release materials. Vancomycin, a potent antibiotic used
      in treating osteomyelitis, can be released from silica sol-gels. Herein, we
      describe the synthesis of thin, resorbable, controlled release bactericidal sol
      gel films on a Ti-alloy substrate and determine the effect of processing
      parameters on its degradation and vancomycin release. A close correlation between
      release and degradation rates suggests that film degradation is the main
      mechanism underlying the control of release. Using a multi-layer process and
      various concentrations of vancomycin, released concentrations exceed the minimal
      inhibitory concentration (MIC) of vancomycin against Staphylococcus aureus. The
      findings enable the tailoring of release and degradation properties of the films
      to therapeutic needs by controlling sol-gel processing parameters. Given the
      bactericidal properties of released vancomycin, and the biocompatibility of the
      sol-gel films, the present data suggest great promise to prevent and treat bone
      infections in a clinical setting.

PMID- 17184836
TI  - Modulation of protein delivery from modular polymer scaffolds.
AB  - Growth factors are increasingly employed to promote tissue regeneration with
      various biomaterial scaffolds. In vitro release kinetics of protein growth
      factors from tissue engineering scaffolds are often investigated in aqueous
      environment, which is significantly different from in vivo environment. This
      study investigates the release of model proteins with net-positive (histone) and
      net-negative charge (bovine serum albumin, BSA) from various scaffolding surfaces
      and from encapsulated microspheres in the presence of ions, proteins, and cells.
      The release kinetics of proteins in media with varying concentrations of ions
      (NaCl) suggests stronger electrostatic interaction between the positively charged
      histone with the negatively charged substrates. While both proteins released
      slowly from hydrophobic PCL surfaces, plasma etching resulted in rapid release of
      BSA, but not histone. Interestingly, although negatively charged BSA released
      readily from negatively charged collagen (col), BSA released slowly from col
      coated PCL scaffolds. Such electrostatic interaction effects were abolished in
      the presence of serum proteins and cells as evidenced by the rapid release of
      proteins from col-coated scaffolds. To achieve sustained release in the complex
      environment of serum proteins and cells, the model proteins were encapsulated
      into poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres, which were embedded
      within col-coated PCL scaffolds. Protein release from microspheres was modulated
      by changing the lactide-to-glycolide ratio of PLGA polymer. BSA adsorbed to col
      released faster than histone encapsulated in microspheres in the presence of
      serum and cells. Collectively, the data suggest that growth factor release is
      highly influenced by scaffold surface and the presence of ions, proteins, and
      cells in the media. Strategies to deliver multiple growth factors and studies
      which investigate their release should consider these important variables.

PMID- 17184837
TI  - Biocidal efficacy, biofilm-controlling function, and controlled release effect of
      chloromelamine-based bioresponsive fibrous materials.
AB  - In this study, 2-amino-4-chloro-6-hydroxy-s-triazine (ACHT) was synthesized
      through controlled hydrolysis of 2-amino-4,6-dichloro-s-triazine (ADCT). A simple
      pad-dry-cure approach was employed to immobilize ACHT onto cellulosic fibrous
      materials. After treatment with diluted chlorine bleach, the covalently bound
      ACHT moieties were transformed into chloromelamines. The structures of the
      samples were fully characterized with NMR, UV/VIS, DSC, TG, iodometric titration
      and elemental analyses. The chloromelamine-based fibrous materials provided
      potent, durable, and rechargeable biocidal functions against bacteria (including
      multi-drug resistant species), yeasts, viruses, and bacterial spores. SEM studies
      demonstrated that the new fibrous materials could effectively prevent the
      formation of biofilms, and controlled release investigations in vitro suggested
      that the biocidal activities were bioresponsive. Biocidal mechanisms of the
      chloromelamine-based fibrous materials were further discussed.

PMID- 17184838
TI  - A novel function of capsaicin-sensitive TRPV1 channels: involvement in cell
      migration.
AB  - Cell migration relies on a tight temporal and spatial regulation of the
      intracellular Ca2+ concentration ([Ca2+]i). [Ca2+]i in turn depends on Ca2+
      influx via channels in the plasma membrane whose molecular nature is still
      largely unknown for migrating cells. A mechanosensitive component of the Ca2+
      influx pathway was suggested. We show here that the capsaicin-sensitive transient
      receptor potential channel TRPV1, that plays an important role in pain
      transduction, is one of the Ca2+ influx channels involved in cell migration.
      Activating TRPV1 channels with capsaicin leads to an acceleration of human
      hepatoblastoma (HepG2) cells pretreated with hepatocyte growth factor (HGF). The
      speed rises by up to 50% and the displacement is doubled. Patch clamp experiments
      revealed the presence of capsaicin and resiniferatoxin (RTX)-sensitive currents.
      In contrast, HepG2 cells kept in the absence of HGF are not accelerated by
      capsaicin and express no capsaicin- or RTX-sensitive current. The TRPV1
      antagonist capsazepine prevents the stimulation of migration and inhibits
      capsaicin-sensitive currents. Finally, we compared the contribution of capsaicin
      sensitive TRPV1 channels to cell migration with that of mechanosensitive TRPV4
      channels that are also expressed in HepG2 cells. A specific TRPV4 agonist, 4alpha
      phorbol 12,13-didecanoate, does not increase the displacement. In summary, we
      assigned a novel role to capsaicin-sensitive TRPV1 channels. They are important
      Ca2+ influx channels required for cell migration.

PMID- 17184839
TI  - Dual treatment with FLT3 inhibitor SU11657 and doxorubicin increases survival of
      leukemic mice.
AB  - FLT3 is mutated in roughly 30% of human AML. We used our model of APL with
      activated FLT3 to assess the effectiveness of chemotherapy in combination with
      SU11657, an inhibitor of FLT3. We found that median survival of untreated and
      doxorubicin-treated mice was not significantly different. While SU11657 alone
      increased median of survival to 55 days (P=0.01), dual therapy increased median
      survival to 62 days (P=0.003) when compared to controls. Neither agent alone or
      in combination increased survival of control mice. These results suggest that the
      use of targeted therapeutics can overcome resistance to traditional
      chemotherapies in AML.

PMID- 17184840
TI  - Endophthalmitis after uncomplicated cataract surgery with the use of fourth
      generation fluoroquinolones: a retrospective observational case series.
AB  - OBJECTIVE: To estimate the rate of acute postoperative endophthalmitis after
      uncomplicated cataract surgery in patients treated before and after surgery with
      1 of 2 different fourth-generation fluoroquinolone ophthalmic drops for surgical
      prophylaxis. DESIGN: Retrospective, multicenter, observational case series.
      PARTICIPANTS: Included in this study were 20,013 patients from 9 cataract surgery
      centers in 7 states in the United States. METHODS: Patients who had undergone
      uncomplicated phacoemulsification who received preoperative and postoperative
      topical fourth-generation fluoroquinolones for surgical prophylaxis between March
      2003 and July 2005 were included in the study. The files of patients in whom
      acute endophthalmitis developed were reviewed and analyzed. MAIN OUTCOME
      MEASURES: Number and rate of endophthalmitis cases after uncomplicated cataract
      surgery. RESULTS: During the study period, the participating surgeons performed
      20,013 uncomplicated surgeries. Of these, 16,209 patients (81%) received topical
      gatifloxacin and 3804 patients (19%) were treated with topical moxifloxacin as
      antiinfective prophylaxis. A total of 14 patients experienced endophthalmitis.
      The overall rate of endophthalmitis was 0.07%. There were 9 endophthalmitis
      patients in the gatifloxacin group and 5 endophthalmitis patients in the
      moxifloxacin group. The rate of endophthalmitis in the gatifloxacin group was
      0.06% and the rate in the moxifloxacin group was 0.1%. The difference in the rate
      of endophthalmitis between the 2 groups was not statistically significant. In 10
      of the patients, vitreous culture results were positive. Coagulase-negative
      staphylococci, followed by streptococci, species were the most commonly isolated
      organisms in the culture-positive patients. CONCLUSIONS: The overall rate of
      endophthalmitis after uncomplicated cataract surgery in patients treated with
      topical fourth-generation fluoroquinolones as antiinfective prophylaxis was
      0.07%. This rate was within the range of previously reported rates of
      endophthalmitis in the literature. The difference in the observed rate of
      postoperative endophthalmitis in patients treated with moxifloxacin versus
      gatifloxacin was not statistically significant.

PMID- 17184841
TI  - Acute retinal necrosis features, management, and outcomes.
AB  - OBJECTIVE: To determine the viral diagnosis and factors affecting the visual
      outcome of eyes with acute retinal necrosis. DESIGN: Nonrandomized,
      retrospective, interventional, noncomparative series. PARTICIPANTS: A cohort of
      22 human immunodeficiency virus-negative patients with acute retinal necrosis
      (ARN). There were 17 unilateral and 5 bilateral cases. INTERVENTION: Diagnostic
      vitreous biopsy for polymerase chain reaction (PCR) viral DNA analysis,
      prophylactic barrier laser posterior to necrotic retina to try to prevent
      rhegmatogenous retinal detachment (RD), intravenous acyclovir in combination with
      oral, and vitrectomy for RD repair. MAIN OUTCOME MEASURES: Results of PCR viral
      DNA analysis, relationship between prophylactic barrier argon laser
      photocoagulation and occurrence of RD, and visual acuities at presentation and
      follow-up. RESULTS: Varicella-zoster virus (VZV) was detected in 66.7% (12/18) of
      eyes (66.7% of patients [10/15]) with vitreous biopsy and herpes simplex virus
      (HSV) in 22.2% (4/18) of eyes (20% of patients [3/15]). Epstein-Barr virus (EBV)
      was detected in 16.7% (3/18) of eyes (20% of patients [3/15]), and all the EBV
      positive eyes were also positive for VZV. Polymerase chain reaction results were
      identical in both eyes of bilateral cases (5 patients) and were negative in 11.1%
      (2/18) of eyes (13.3% of patients [2/15]) biopsied. Systemic corticosteroid
      treatment given before ARN diagnosis did not appear to increase the risk of
      developing RD (P = 0.69). Rhegmatogenous RD occurred in 35.3% (6/17) of eyes
      given prophylactic argon laser treatment and in 80% (8/10) of eyes that could not
      be lasered prohylactically. Of RDs, 96.3% (13/14) occurred after the third week
      and up to 5 months from onset of symptoms. The VA after surgical repair of RD
      improved relative to the presentation acuity in 33.3% (4/12) of eyes. CONCLUSION:
      Varicella-zoster virus is the leading cause of ARN. We recommend the management
      of ARN to include prompt diagnosis; prophylactic argon laser retinopexy,
      preferably within the first 2 weeks to reduce risk of RD; systemic acyclovir; and
      corticosteroids to control the severe inflammation associated with ARN. Despite
      the guarded visual prognosis, RD repair may result in improved visual outcomes.

PMID- 17184842
TI  - Simultaneous labeling of projecting neurons and apoptotic state.
AB  - We describe a straightforward method that accomplishes both the labeling of
      projecting neurons and the identification of apoptosis in those neurons. A single
      dye, 4',6-diamidino-2-phenylindole (DAPI), is both retrogradely transported and
      binds DNA. When delivered to the sites of neuronal projections, DAPI travels via
      retrograde transport from neuronal projections to the soma and stain nuclei with
      little or no cytoplasmic labeling. The staining of the nuclei allows for
      visualization of their morphological characteristics; DAPI-stained living cells
      appear markedly different from DAPI-stained apoptotic cells, due to the nuclear
      changes that apoptotic cells undergo. This technique has been successfully
      employed with retinal ganglion cells in the retinocollicular pathway. The use of
      a single dye not only eliminates the need for secondary staining for apoptosis,
      but also allows for the use of a wider variety of non-overlapping fluorescent
      dyes for other studies.

PMID- 17184844
TI  - Long-term outcome of depressive pseudodementia in the elderly.
AB  - BACKGROUND: The term depressive pseudodementia has proved to be a popular
      clinical concept. Little is known about the long-term outcome of this syndrome.
      AIMS: To compare depressed elderly patients with reversible cognitive impairment
      and cognitively intact depressed elderly patients. METHODS: All patients
      suffering from moderate or severe depression admitted to St Margaret's Hospital,
      UK as inpatients or day hospital outpatients between January 1 1997 and December
      31 1999 (n=182) were screened for entry into the study. Eligible patients were
      divided into those presenting with pseudodementia and those who were cognitively
      intact and followed up for 5 to 7 years. RESULTS: Seventy-one point four percent
      of those suffering from pseudodementia had converted into dementia at follow-up
      compared to only 18.2% in the cognitively intact group. The relative risk was
      3.929 (95% CI: 1.985 to 7.775) and the 'number needed to harm' 1.88. CONCLUSIONS:
      Reversible cognitive impairment in late-life moderate to severe depression
      appears to be a strong predictor of dementia. Inpatients and day hospital
      outpatients with depressive pseudodementia should probably have a full dementia
      screening, comprehensive cognitive testing and ongoing monitoring of their
      cognitive function.

PMID- 17184843
TI  - Associations between cod liver oil use and symptoms of depression: the Hordaland
      Health Study.
AB  - BACKGROUND: Clinical trials suggest that omega-3 fatty acids improve the outcome
      of depression. This study aimed to evaluate the association between intake of cod
      liver oil, rich in omega-3 fatty acids, and high levels of symptoms of depression
      and anxiety in the general population. METHODS: We used data from the "The
      Hordaland Health Study '97-'99" (HUSK), a population based cross-sectional health
      survey from Norway including 21,835 subjects aged 40-49 and 70-74 years. Symptoms
      of depression and anxiety were measured by The Hospital Anxiety and Depression
      Scale (HADS). We used logistic regression to study associations. RESULTS: Among
      the participants, 8.9% used cod liver oil daily. A total of 3.6% had high levels
      of depressive symptoms. The prevalence of such depressive symptoms among the
      subjects who used cod liver oil daily was 2.5%, as compared to 3.8% in the rest
      of the population. The users of cod liver oil were significantly less likely to
      have depressive symptoms than non-users after adjusting for multiple possible
      confounding factors (odds ratio=0.71, 95% confidence interval 0.52 to 0.97).
      These factors included age, gender, smoking habits, coffee consumption, alcohol
      consumption, physical activity, and education. In addition, we found that the
      prevalence of high levels of depressive symptoms decreased with increasing
      duration (0-12 months) of cod liver oil use (multivariate adjusted test for
      trend, P=0.04). We were only able to study this latter association in a subset of
      the population aged 40-46 years. LIMITATIONS: Data are cross sectional.
      CONCLUSIONS: The findings indicate that regular use of cod liver oil is
      negatively associated with high levels of depressive symptoms in the general
      population.

PMID- 17184845
TI  - Primary cytomegalovirus infection in patients with Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is frequently associated with the presence of CMV
      specific IgM-antibodies or CMV-DNA in serum. Detection of IgM-antibodies or
      viremia may indicate primary infection, but also reactivation or reinfection. We
      identified 46 GBS patients with detectable CMV-specific IgM- or IgG-antibodies,
      or both. Sera from these patients were tested for the presence of CMV-specific,
      low-avidity IgG-antibodies, which indicate primary infection that occurred <6
      months before sample collection, and for the presence of CMV-DNA by polymerase
      chain reaction (PCR). Primary infection was identified by the presence of low
      avidity IgG-antibodies in 9/46 (20%) or by detection of IgM-antibodies in the
      absence of IgG-antibodies in 1/46 (2%) patients. CMV-DNA was detectable in 17/46
      (37%) sera. In contrast, CMV-DNA was detected in only 2% of sera from 46 age
      matched patients with neuroborreliosis. The likelihood of viremia decreased in
      GBS patients significantly with increasing antibody-avidity (P=0.041). Detection
      of IgM-antibodies correlated with that of CMV-DNA in patients with low-avidity
      IgG-antibodies (P=0.048) but not in those with high-avidity IgG-antibodies
      (P=0.543). In 45 age-matched healthy controls, low-avidity IgG-antibodies and CMV
      DNA were detected in only 2% and 0% of sera, respectively. Our findings further
      strengthen evidence for an association between CMV infection and GBS. Primary CMV
      infection was identified in almost one-fourth of patients with detectable CMV
      specific antibodies. Nevertheless, endogenous reactivation and reinfection have
      to be considered also as relevant events associated with GBS.

PMID- 17184847
TI  - Interleukin-10 reduces hyperalgesia and the level of Interleukin-1beta in BALB/c
      mice infected with Leishmania major with no major effect on the level of
      Interleukin-6.
AB  - Infection with a high dose of Leishmania major has been shown to induce
      hyperalgesia in BALB/c mice accompanied by a sustained upregulation of
      Interleukin-1beta (IL-1beta) and an early upregulation of Interleukin-6 (IL-6).
      On the other hand, Interleukin 10 (IL-10) has been demonstrated to be hypoalgesic
      in other models such as rats exposed to UV rays. In this study, we injected
      BALB/c mice with a high dose of Leishmania major and treated them with IL-10 (15
      ng/animal) for six consecutive days. Hyperalgesia was assessed using thermal pain
      tests and the levels of IL-1beta and IL-6 were also assessed at different post
      infection days. Our results show that IL-10 can reduce the Leishmania major
      induced hyperalgesia during the treatment period through a direct effect on the
      levels of IL-1beta which seems to play an important role in this hyperalgesia
      induction since its level was reduced during the period of IL-10 injection and
      was increased again when this treatment was stopped. On the contrary IL-10 has no
      direct effect on the levels IL-6 which seems to have no direct role in the
      induced hyperalgesia.

PMID- 17184846
TI  - In situ immune response in brain and kidney during early relapsing fever
      borreliosis.
AB  - Characterization of the host immune response during initial pathogenesis of
      relapsing fever neuroborreliosis would be a key to understanding Borrelia
      persistence and factors driving the inflammatory process. We analyzed immune
      cells in brain and kidney with the highly invasive B. crocidurae during the first
      two weeks of murine infection. In both organs, microglia and/or macrophages
      predominated while T-cell changes were minimal. Compared to kidney, brain
      neutrophils infiltrated more rapidly and B-cells were essentially absent. Our
      results indicate that during early neuroborreliosis, brain defense is comprised
      primarily of innate immune cells while adaptive immunity plays a minor role.

PMID- 17184848
TI  - Healthcare givers' skill and foreign bodies in the ears of children in the
      tropics.
AB  - OBJECTIVE: The aim is to find out the place of clinical skill in the management
      of foreign bodies in the ear of children by various healthcare givers. METHOD:
      Case files of children with foreign bodies in the ears seen in the
      Otorhinolaryngology Department of University College Hospital, Ibadan, Nigeria
      from 1996 to 2005 were reviewed for all essential clinical data. RESULT: Of 323
      patients studied, 171 (53.00%) males and 152 (47.00%) females, 168 (52.01%) had
      prior removal attempts done by anxious caregivers or general practitioners before
      referral; 154 (91.67%) of these had complications. Only 10 (6.45%) of the 155
      (47.99%) with removal by ENT registrars had complications. CONCLUSION:
      Complications found appear to be related to level of clinical skill of individual
      health caregiver. Wherever possible, first attempt at removing aural foreign
      bodies should be done by an otorhinolaryngologist. Anxious parents must be
      discouraged from attempts but if they must attempt to remove ear foreign body, it
      must be by a safe ear syringing. General practitioners must be aware of their
      limitations and ENT registrars must be supervised by senior registrars with help
      of operating microscope to remove foreign bodies from the ears.

PMID- 17184849
TI  - An RNA extraction protocol for shellfish-borne viruses.
AB  - The GPTT virus RNA extraction method, originally developed for extraction of
      human norovirus and hepatitis A virus RNAs from contaminated shellfish, was
      evaluated for extraction of RNA from Aichi virus strain A846/88 (AiV),
      coxsackievirus strains A9 (CAV9) and B5 (CBV5), murine norovirus (strain MNV-1),
      and the norovirus surrogate, feline calicivirus (FCV) strain KCD, for the purpose
      of RT-PCR detection within seeded oyster (Crassostrea virginica) extracts. The RT
      PCR equivalent sensitivities observed within seeded oysters as compared to virus
      stocks were 0.68, 6.8, 26, 5.6, and 14.5 RT-PCR(50) units when assaying 10% of
      total RNA extracted from seeded oyster extracts for CAV9, CBV5, AiV, FCV, and MNV
      1, respectively. For oysters exposed to virus-contaminated seawater, the
      detection equivalent sensitivities observed were 680, 68, 2600, 560, and 14.5 RT
      PCR(50) for CAV9, CBV5, AiV and FCV, and MNV-1, respectively. These results
      indicate that the GPTT method can be used as a general viral RNA extraction
      method for multiple picornaviruses and caliciviruses that could potentially
      contaminate shellfish.

PMID- 17184850
TI  - Duplex nested RT-PCR for detection of Nipah virus RNA from urine specimens of
      bats.
AB  - A method for duplex nested RT-PCR (nRT-PCR) with internal control (IC) for the
      detection of Nipah virus RNA is described. Incorporation of IC RNA distinguished
      false and true negative results. The extrinsic RNA was added directly to the PCR
      master mix and co-amplified with virus specific RNA in a duplex reaction to
      determine the presence of PCR inhibitor. Limit of detection was affected
      minimally when IC was added. Of 53 pooled urine samples collected from fruit bats
      (Pteropus lylei), 16 were validated by the presence of IC band on gel
      electrophoresis. Seven of these were also Nipah virus RNA positive. The remaining
      37 samples were considered invalid. Twenty-two urine samples became valid after
      dilution of 1:5 and re-examined; two were Nipah virus RNA positive. These nine
      positive results were confirmed by sequencing of heminested PCR products. The
      result indicated that at least two different Nipah strains circulated in this bat
      species from Thailand. This method should be useful for surveillance for Nipah
      virus infection in animals in a country where a biosecurity level (BSL) 4
      laboratory is not available. PCR inhibitors were present in a significant number
      of bat urine samples. The technique described in this study should improve
      reliability of surveillance statistics.

PMID- 17184851
TI  - Infection, transfection, and co-transfection of baculoviruses by microprojectile
      bombardment of larvae.
AB  - The use of baculoviruses as expression vectors for heterologous proteins has been
      practically limited to the use of the Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV). In this work, infection, transfection and co
      transfection events with the baculoviruses AcMNPV and Trichoplusia ni
      granulovirus (TnGV) were accomplished by bombardment of T. ni first-instar larvae
      with microprojectiles coated with virions, viral DNA, and viral DNA and a
      transfer vector, respectively. A series of shooting conditions were tested until
      positive results were obtained. The use of 1.6 microm gold particles at 900 psi
      shooting pressure, 400 Torr vacuum, 7 cm distance to target, on sets of 20 first
      instar larvae held in a 16 mm diameter container, proved to be the best shooting
      conditions. Typical infection symptoms were shown by larvae when shot with
      viruses or viral DNA from AcMNPV or TnGV. Co-transfected recombinant AcMNPV and
      TnGV were identified by the formation of occlusion bodies and GFP, respectively,
      in bombarded larvae. This technique opens a wide range of possibilities, not only
      to use an extensive number of baculoviruses as expression vectors for
      heterologous proteins, but also be used to infect, transfect or co-transfect a
      wide variety of viruses into animal cells.

PMID- 17184852
TI  - A nucleotide sequence variation detection system for the core region of hepatitis
      C virus-1b.
AB  - Amino-acid substitution at positions 70 and 91 of the hepatitis C virus (HCV)-1b
      core region is a factor that contributes to a non-virological response in
      treatment using interferon/ribavirin combination. In this study, a system was
      developed for detection of nucleotide sequence variation in the core region that
      is simpler and less expensive than the current direct sequencing method. A PCR
      detection method using mutation-specific primers was developed, and amino acids
      at positions 70 and 91 were identified. The protein type was determined based on
      band intensity in electrophoresis, and classified into wild (70:R, 91:L), mutant
      (70:Q/H, 91:M) and competitive types. The detection rate, sensitivity and
      reproducibility were investigated in 108 patients with HCV-1b who were treated
      with interferon/ribavirin combination therapy, and correlation with the results
      of direct sequencing was examined. The detection rate was 94.4%, the sensitivity
      was 10 KIU/mL, the reproducibility was high, and in detectable cases the
      consistency with direct sequencing was 97.1%; inconsistency was noted in two
      competitive-type cases and in one case with an unusual amino-acid substitution.
      The results suggest that the system described in this paper provides an
      effective, simple and low-cost approach to detection of nucleotide sequence
      variation in the core region of HCV-1b.

PMID- 17184853
TI  - Evaluation of performance across the dynamic range of the Abbott RealTime HIV-1
      assay as compared to VERSANT HIV-1 RNA 3.0 and AMPLICOR HIV-1 MONITOR v1.5 using
      serial dilutions of 39 group M and O viruses.
AB  - Performance of the Abbott m2000 instrument system and the Abbott RealTime HIV-1
      assay was evaluated using a panel of 37 group M (subtypes A-D, F, G, CRF01_AE,
      CRF02_AG and unique recombinant forms) and 2 group O virus isolates. Testing was
      performed on 273 sample dilutions and compared to VERSANT HIV-1 RNA 3.0 (bDNA)
      and AMPLICOR HIV-1 MONITOR v1.5 (Monitor v1.5) test results. RealTime HIV-1,
      bDNA, and Monitor v1.5 tests quantified 87%, 78%, and 81% of samples,
      respectively. RealTime HIV-1 detected an additional 31 samples at < 40 copies/mL.
      For group M, RealTime HIV-1 dilution profiles and viral loads were highly
      correlated with bDNA and Monitor v1.5 values; 87% and 89% of values were within
      0.5 log(10) copies/mL. In contrast, the group O viruses were not detected by
      Monitor v1.5 and were substantially underquantified by approximately 2 log(10)
      copies/mL in bDNA relative to the RealTime HIV-1 assay. Sequence analysis
      revealed that RealTime HIV-1 primer/probe binding sites are highly conserved and
      exhibit fewer nucleotide mismatches relative to Monitor v1.5. The automated m2000
      system and RealTime HIV-1 assay offer the advantages of efficient sample
      processing and throughput with reduced "hands-on" time while providing improved
      sensitivity, expanded dynamic range and reliable quantification of genetically
      diverse HIV-1 strains.

PMID- 17184854
TI  - In vitro evaluation of the anti-orf virus activity of alkoxyalkyl esters of CDV,
      cCDV and (S)-HPMPA.
AB  - Acyclic nucleoside phosphonates (ANPs) and in particular (S)-1-[3-hydroxy-2
      (phosphonomethoxy)propyl]cytosine (HPMPC, cidofovir, CDV, Vistide) and its
      adenine counterpart (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)
      HPMPA] are highly active against orf virus infections. This parapoxvirus commonly
      causes infection in sheep, goats, but also humans. Alkoxyalkyl esters of CDV have
      an increased oral bioavailability and are more active against orthopoxviruses
      than the parent compounds. In the present study, the potency of several
      alkoxyalkyl esters of CDV, cyclic cidofovir (cCDV) and (S)-HPMPA was evaluated
      against different orf virus isolates in two cell types, human embryonic lung
      (HEL) fibroblast and primary lamb keratinocytes. Each prodrug was at least 10
      fold more active than its parent compound in both cell types. Of all the
      compounds tested, the (S)-HPMPA alkoxyalkyl esters showed the highest activity
      and selectivity against orf virus. Our results support the development of
      alkoxyalkyl esters of ANPs as antivirals not only for the treatment of
      complicated human orf lesions, but also in the therapy and prophylaxis of
      contagious ecthyma in sheep and goats.

PMID- 17184856
TI  - Leptin deficiency leads to the regulation of kinin receptors expression in mice.
AB  - Kinins are vasoactive and pro-inflammatory peptides generated by the cleavage of
      the kininogen by kallikreins. Two kinin receptors have been described and
      denominated B1 and B2. Obesity frequently accompanies other pathologies, such as
      diabetes and hypertention. The clustering of these pathologies is usually known
      as "metabolic syndrome". Mice lacking leptin gene (ob/ob) are severely obese and
      hyperphagic. Using quantitative RT-PCR analysis of B1 and B2 mRNAs expression, we
      described for the first time a correlation between the kallikrein-kinin system
      (KKS) and severe obesity in mice. The ob/ob mice presented lower expression of B2
      mRNA in the white adipose tissue (WAT) and hypothalamus, both primary sites for
      neuroendocrine regulation of the energetic metabolism. B1 mRNA, however, is
      overexpressed in these tissues of ob/ob mice. An upregulation of the B1 mRNA has
      also been seen in liver, abdominal aorta and stomach fundus. However, different
      from the lean mice, the expression of the B1 mRNA in brown adipose tissue (BAT)
      and heart is completely abolished. Our data show that kinin receptors are
      differently modulated in distinct tissues in obesity. These findings suggest a
      connection between the KKS and obesity, and suggest that kinin receptors could be
      involved in the ethiopathogenesis of the metabolic syndrome.

PMID- 17184857
TI  - Fall-related injuries among initially 75- and 80-year old people during a 10-year
      follow-up.
AB  - The aim of this study was to investigate the occurrence, type, scene and seasonal
      variation of fall related injuries, and the impact of socio-economic factors,
      mobility limitation, and the most common diseases on the risk of injurious falls
      over a 10-year follow-up. Elderly residents of Jyvaskyla, Finland, aged initially
      75 and 80 years, took part in the study in 1989-1990. The health and functional
      capacity assessments were carried out at the baseline. Injurious falls were
      monitored over a 10-year period. The rate of injurious falls per thousand person
      years was 188 among women and 78 among men. Of all fall-related diagnoses, head
      injuries comprised 32%, upper limb injuries 27% and hip injuries 19%. Majority of
      injurious falls took place indoors and no seasonal variation in fall occurrence
      was observed. Recurring falls were more likely to take place in institutions.
      Osteoarthritis increased the risk of injurious falls but no effect was observed
      for coronary heart diseases or mobility limitation. All in all, intrinsic
      factors, such as chronic diseases and mobility limitation had only minor effect
      on risk of injurious falls among older people. The current results suggest that
      preventive interventions for injurious falls among older people should pay
      attention to the risk factors present indoors.

PMID- 17184855
TI  - Characterization of hepatic glutathione S-transferases in coho salmon
      (Oncorhynchus kisutch).
AB  - The glutathione S-transferases (GSTs) are a family of phase II detoxification
      enzymes which protect against chemical injury. In contrast to mammals, GST
      expression in fish has not been extensively characterized, especially in the
      context of detoxifying waterborne pollutants. In the Northwestern United States,
      coho salmon (Oncorhynchus kisutch) are an important species of Pacific salmon
      with complex life histories that can include exposure to a variety of compounds
      including GST substrates. In the present study we characterized the expression of
      coho hepatic GST to better understand the ability of coho to detoxify chemicals
      of environmental relevance. Western blotting of coho hepatic GST revealed the
      presence of multiple GST-like proteins of approximately 24-26kDa. Reverse phase
      HPLC subunit analysis of GSH affinity-purified hepatic GST demonstrated six major
      and at least two minor potential GST isoforms which were characterized by liquid
      chromatography electrospray ionization tandem mass spectrometry (LC/ESI MS-MS)
      and Fourier transform-ion cyclotron resonance (FT-ICR) MS analyses. The major
      hepatic coho GST isoforms consisted of a pi and a rho-class GST, whereas GSTs
      representing the alpha and mu classes constituted minor isoforms. Catalytic
      studies demonstrated that coho cytosolic GSTs were active towards the
      prototypical GST substrate 1-chloro-2,4-dinitrobenzene, as well as towards
      ethacrynic acid and nitrobutyl chloride. However, there was no observable
      cytosolic GST activity towards the pesticides methyl parathion or atrazine, or
      products of oxidative stress, such as cumene hydroperoxide and 4-hydroxynonenal.
      Interestingly, coho hepatic cytosolic fractions had a limited ability to bind
      bilirubin, reflecting a potential role in the sequestering of metabolic by
      products. In summary, coho salmon exhibit a complex hepatic GST isoform
      expression profile consisting of several GST classes, but may have a limited a
      capacity to conjugate substrates of toxicological significance such as pesticides
      and endogenous compounds associated with cellular oxidative stress.

PMID- 17184859
TI  - Improvement of the detection of myocardial ischemia thanks to information
      technologies.
AB  - BACKGROUND: The standard 12-lead ECG remains one of the basic investigations for
      the early detection and assessment of acute coronary syndromes. It is easy to
      perform, anywhere and anytime, and can be digitally transmitted within minutes to
      an emergency medical service for remote advice and triage. But the conventional
      ST-segment deviation criteria are of limited diagnostic accuracy. The purpose of
      this study is to investigate how much the use of computerized ECG techniques
      based on the measurement of the serial spatiotemporal ECG changes could improve
      the detection accuracy of transmural myocardial ischemia. METHODS: We considered
      the serial changes of continuous 12-lead ECGs of 90 patients undergoing elective
      percutaneous coronary angioplasty (PTCA) recorded during balloon inflation as an
      experimental model of ECG changes induced by coronary artery occlusion. The
      spatiotemporal ECG changes were measured according to the CAVIAR method and
      assessed by multivariate discriminant analysis in reference to serial changes of
      control recordings and standard ECG criteria. RESULTS: The diagnostic accuracy of
      the CAVIAR criteria for ischemia detection was 97%, with sensitivity of 98% and
      specificity of 96%, whereas the diagnostic accuracy of the conventional ST
      segment criteria was 74%, with sensitivity of 60% and specificity of 88%. The
      increase of overall performance was obtained for all the occlusion locations.
      CONCLUSIONS: Computer-assisted quantitative serial ECG analysis, taking into
      account the spatiotemporal changes of the QRS and T waves, would provide the
      physician with additional information for significantly improving the detection
      of transmural myocardial ischemia.

PMID- 17184858
TI  - High mortality in diabetic patients with acute myocardial infarction:
      cardiovascular co-morbidities contribute most to the high risk.
AB  - BACKGROUND: High mortality rates have been reported in diabetic patients after
      acute myocardial infarction (AMI). The excess mortality has been attributed to
      the diabetic state itself. We aimed to investigate how other risk factors along
      with diabetes per se may predict mortality in an unselected AMI population.
      METHODS: A representative sample of an unselected AMI population was collected
      over a three-month period. Data on patients' histories, co-morbidity, presenting
      features and treatment were collected from medical records. The data sets
      included outcome variables at discharge, after 6 months and after 2.5 years.
      Patients with confirmed diabetes on admission to hospital were registered as
      diabetic patients. RESULTS: Of the 901 patients admitted to hospital with AMI,
      121 (14%) were diabetic patients. Compared with the nondiabetic patients
      significantly fewer of the diabetic patients were alive at discharge (78% vs
      86%), after 6 months (64% vs 78%) and after 2.5 years (42% vs 65%). In multiple
      logistic regression analyses adjusted for age, sex and smoking status, the most
      important predictor of death at 2.5 years was heart failure, followed by previous
      MI, diabetes, and angina pectoris. The population attributable risk (PAR) of
      death after 2.5 years was 7% for diabetes, 17% for previous MI, 13% for heart
      failure and 12% for angina pectoris. CONCLUSION: Among patients with diabetes
      suffering an AMI the already established cardiovascular co-morbidities, which
      previously partly or fully might have been caused by diabetes, contributed more
      than diabetes per se to high mortality in-hospital and in the follow-up period.

PMID- 17184860
TI  - Discrimination and characterization of environmental strains of Escherichia coli
      by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS).
AB  - A rapid and reliable bacterial source tracking (BST) method is essential to
      counter risks to human health posed by fecal contamination of surface waters.
      Genetic fingerprinting methods, such as repetitive sequence based-PCR (rep-PCR),
      have shown promise as BST tools but are time-consuming and labor-intensive. In
      this work, we investigate the ability of MALDI-TOF-MS to characterize and
      discriminate between closely related environmental strains of Escherichia coli
      and to classify them according to their respective sources. We compared the
      performance of a rapid MALDI-TOF-MS-based method to a commonly used rep-PCR-based
      method that employs the BOX-A1R primer. Among the criteria evaluated were
      repeatability and the ability of each method to group E. coli isolates according
      to their respective sources. Our data suggest that the MALDI-TOF-MS-based
      approach has a lower repeatability level compared to rep-PCR but offers an
      improved ability to correctly assign E. coli isolates to specific source groups.
      In addition, we have identified five biomarkers that appear conserved among avian
      species. We conclude that MALDI-TOF-MS may represent a promising, novel and rapid
      approach to addressing the problem of fecal contamination of surface waters and
      warrants further investigation.

PMID- 17184861
TI  - Estimating amplification efficiency improves multiplex real-time PCR
      quantification of Bacillus licheniformis and Bacillus subtilis spores in animal
      feed.
AB  - A multiplex real-time PCR assay was developed for absolute quantification in
      animal feed of Bacillus subtilis CH201 and Bacillus licheniformis CH200 spores,
      which constitute the viable component of the microbial growth promoter, BioPlus
      2B. Spores were lysed using a bead-beating protocol. DNA was extracted and
      purified from the lysates with the Qiagen DNeasy Plant Kit. Two standard curves
      for absolute quantification were made and tested. Standard curve-1 was made from
      feed samples spiked with BioPlus 2B, while standard curve-2 was made from
      serially diluted DNA extracted from BioPlus 2B powder. Feed samples supplemented
      with BioPlus 2B were quantified using both standard curves. The detection limit
      of the assay was 10(4) CFU g(-1) of feed. The amplification efficiency (Eff) of
      each PCR was determined using the LinRegPCR software and Eff differences between
      individual samples and standards were corrected for. When compared to plate
      counts, standard curve-1 slightly under-estimated the number of spores (mean=
      2.47% of plate counts). A spore density-dependent Eff was found, and Eff for
      standard curve-1 could not be determined. Standard curve-2 over-estimated spore
      numbers when not corrected for individual Eff (mean=+5.46% of plate counts).
      Standard curve-2 Eff was independent (Eff(mean)=1.96) of spore density. The assay
      quantified the numbers of spores in feed samples very similar to plate counts
      (mean=+0.47% of plate counts), when standard curve-2 was used and individual Eff
      was accounted for.

PMID- 17184862
TI  - Biocatalysis for pharmaceutical intermediates: the future is now.
AB  - Biocatalysis is continuing to gain momentum and is now becoming a key component
      in the toolbox of the process chemist, with a place alongside chemocatalysis and
      chromatographic separations. The pharmaceutical industry demands a speed of
      development that must be on a parallel with conventional chemistry and high
      optical purity for complex compounds with multiple chiral centres. This review
      describes how these demands are being addressed to make biocatalysis successful,
      particularly by the use of micro-scale technology for high-speed catalyst
      screening and process development alongside discipline integration of biology and
      engineering with chemistry. Developments in recombinant technology will further
      expand the repertoire of biocatalysis in the coming years to new chemistries and
      enable catalyst design to fit the process. Further development of biocatalysis
      for green chemistry and high productivity processes can also be expected.

PMID- 17184863
TI  - Is this the swan song of endovascular brachytherapy?

PMID- 17184864
TI  - Anaphylactoid reaction from amifostine.

PMID- 17184865
TI  - Blocking the glial function suppresses subcutaneous formalin-induced nociceptive
      behavior in the rat.
AB  - This study examined whether glial cells in the trigeminal nucleus caudalis (Sp5C)
      were necessary for orofacial nociception and nociceptive processing induced by
      subcutaneously (s.c.) injection of 5% formalin into left mystacial vibrissae. The
      immunohistochemical, immunoelectron microscopical methods and behavior assessment
      were used in this study. Two hours after administration of carbenoxolone (CBX, a
      gap junction blocker) or fluorocistrate (FCA, a glail metabolic inhibitor) into
      the cerebellomedullary cistern, the nociceptive behavior and scratching
      cumulative time reduced significantly (P<0.01). FCA attenuated obviously the
      expression of Fos/NeuN-immunoreactive (-IR) neurons (mean+/-S.E.M.=29+/-2.5) and
      Fos/glial fibrillary acidic protein (GFAP)-IR astrocytes (7.2+/-2.2) in Sp5C. CBX
      decreased the number of Fos/NeuN-IR neurons (25+/-1.7), but did not affect
      Fos/GFAP-IR astrocytes (16.2+/-5.4), compared with vehicle-preadministered rats
      (Fos/NeuN-IR neurons 135+/-4.2, and Fos/GFAP-IR astrocytes 25.8+/-4).
      Immunoelectron microscopy established that Cx32/Cx43 heterotypic gap junctions
      (HGJs) were present on junction areas between astrocytes and neurons within Sp5C.
      The number of HGJs increased significantly following formalin s.c. injection. It
      suggests that the Sp5C astrocytes may play an active regulating role in orofacial
      nociception via Cx32/Cx43 HGJs between astrocytes and neurons of Sp5C.

PMID- 17184866
TI  - Influence of pH, water activity and acetic acid concentration on Listeria
      monocytogenes at 7 degrees C: data collection for the development of a growth/no
      growth model.
AB  - Growth/no growth models can be used to determine the chance that microorganisms
      will grow in specific environmental conditions. As a consequence, these models
      are of interest in the assessment of the safety of foods which can be
      contaminated with food pathogens. In this paper, growth/no growth data for
      Listeria monocytogenes (in a monoculture and in a mixed strain culture) are
      presented. The data were gathered at 7 degrees C in Nutrient Broth with different
      combinations of environmental factors pH (5.0-6.0, six levels), water activity
      (0.960-0.990, six levels) and acetic acid concentration (0-0.8% (w/w), five
      levels). This combination of environmental factors for the development of a
      growth/no growth model was based on the characteristics of sauces and mayonnaise
      based salads. The strains used were chosen from screening experiments in which
      the pH, water activity and acetic acid resistance of 26 L. monocytogenes strains
      (LFMFP culture collection) was determined at 30 degrees C in Brain Heart Infusion
      broth. The screening showed that most L. monocytogenes strains were not able to
      grow at a(w)<0.930, pH<4.3 or a total acetic acid concentration >0.4% (w/w).
      Among these strains, the ones chosen were the most resistant to one of these
      factors in the hope that, if the resulting model predicted no growth at certain
      conditions for those more resistant strains, then these predictions would also be
      valid for the less resistant strains. A mixed strain culture was also examined to
      combine the strains that were most resistant to one of the factors. A full
      factorial design with the selected strains was tested. The experiments were
      performed in microtiter plates and the growth was followed by optical density
      measurements at 380 nm. The plates were inoculated with 6 log CFU/ml and twenty
      replicates were made for each treatment combination. These data were used (1) to
      determine the growth/no growth boundary and (2) to estimate the influence of the
      environmental conditions on the time to detection. From the monoculture and mixed
      strain data, the growth boundary of L. monocytogenes is shown not to be a
      straight cut-off but a rather narrow transition zone. The experiments also showed
      that in the studied region, a(w) did not have a pronounced influence on the
      position of the growth/no growth boundary while a low concentration of acetic
      acid (0.2% (w/w)) and a pH decrease from 6.0 to 5.8 was sufficient to
      significantly reduce the possibility of growth. The determination of the time to
      detection showed a significant increase at the combinations of environmental
      conditions near the 'no growth zone'. For example, at 0.2% (w/w) acetic acid,
      there was an increase from +/-10 days to 30 days by lowering pH from 5.8 to 5.6
      at a(w) values of 0.985 and 0.979, while at pH 5.4 less than 50% growth occurred
      for all a(w) values.

PMID- 17184867
TI  - Rapid removal of lead and cadmium from water by specific lactic acid bacteria.
AB  - Cadmium and lead are highly toxic metals. People are exposed to them primarily
      through food and water. Available conventional methods (precipitation,
      flocculation, ion exchange, and membrane filtration) for removal of these metals
      from water at low concentrations are claimed to be expensive and inefficient.
      Different microbes have been proposed to be an efficient and economical
      alternative in heavy metal removal from water. In this work, specific lactic acid
      bacteria (LAB) were assessed for their ability to remove cadmium and lead from
      water. Significant removal was observed, and it was found to be metal and
      bacterial strain specific. Removal was a fast, metabolism-independent surface
      process. It was also strongly influenced by pH, indicating that ion exchange
      mechanisms could be involved. The most effective metal removers were
      Bifidobacterium longum 46, Lactobacillus fermentum ME3 and Bifidobacterium lactis
      Bb12. The highest maximum cadmium and lead removal capacities of 54.7 mg metal/g
      and 175.7 mg/g dry biomass, respectively, were obtained with B. longum 46.

PMID- 17184868
TI  - Modelling the influence of the sporulation temperature upon the bacterial spore
      heat resistance, application to heating process calculation.
AB  - Environmental conditions of sporulation influence bacterial heat resistance. For
      different Bacillus species a linear Bigelow type relationship between the
      logarithm of D values determined at constant heating temperature and the
      temperature of sporulation was observed. The absence of interaction between
      sporulation and heating temperatures allows the combination of this new
      relationship with the classical Bigelow model. The parameters zT and zT(spo) of
      this global model were fitted to different sets of data regarding different
      Bacillus species: B. cereus, B. subtilis, B. licheniformis, B. coagulans and B.
      stearothermophilus. The origin of raw products or food process conditions before
      a heat treatment can lead to warm temperature conditions of sporulation and to a
      dramatic increase of the heat resistance of the generated spores. In this case,
      provided that the temperature of sporulation can be assessed, this model can be
      easily implemented to rectify F values on account of possible increase of thermal
      resistance of spores and to ensure the sterilisation efficacy.

PMID- 17184869
TI  - Mucosal immunomodulation by the non-bacterial fraction of milk fermented by
      Lactobacillus helveticus R389.
AB  - The health promoting effects ascribed to probiotic bacteria and fermented dairy
      products arise not only from bacteria themselves but also from metabolites
      derived from milk fermentation. Exopolysaccharides produced during milk
      fermentation and peptides derived from major milk proteins, when released during
      fermentation, are potential modulators of various regulatory processes in the
      body. The aim of this work was to increase the knowledge of the previously
      observed immunomodulating capacity of milk fermented by Lactobacillus helveticus
      R389 by the study of the mucosal immunomodulation exerted by the non-bacterial
      fraction of the milk fermented at a constant pH6 (NBFpH6). The effects on IL-6
      production by small intestine epithelial cells, the profile of IgA+ and cytokine+
      cells (IL-2, IL-6, IL-10, TNF-alpha and IFN-gamma) induced in the gut lamina
      propria, and the levels of total and specific secretory IgA in the lumen of
      BALB/c mice that received NBFpH6 for 2, 5 or 7 days were examined. There was an
      increase in the number of IgA+, IL-10+, IL-2+ and IL-6+ cells after all feeding
      periods. Total S-IgA in the small intestine lumen increased in mice that received
      NBFpH6 for 2 days. However, no specific antibodies against NBFpH6 were detected.
      Feeding of NBFpH6 for 7 days significantly (P<0.05) enhanced IL-6 secretion by
      small intestine epithelial cells. NBFpH6 induced a non-specific mucosal response
      that was down-regulated for protective immunity, enhancing IL-6 production by
      epithelial cells and IgA production in the small intestine. These events improve
      the immunological defenses at the intestinal level, increasing host protection
      against pathologies. Because mucosal immune responses induced by certain dietary
      antigens play a large part in the prevention of gastrointestinal diseases, the
      oral administration of a mucosal adjuvant such as NBFpH6 may positively affect
      the milieu of the intestinal lumen. The opportunity exists then to manipulate the
      constituents of the lumen of the intestine through dietary means, thereby
      enhancing the health condition of the host.

PMID- 17184870
TI  - N-sulfonato-N,O-carboxymethylchitosan: a novel polymeric absorption enhancer for
      the oral delivery of macromolecules.
AB  - Chitosan has been shown to act on the mucosal epithelial barriers mainly when
      protonated at acidic pH values in which it is soluble. Soluble chitosan is able
      to improve the permeation and absorption of neutral to cationic macromolecules
      only, as it forms polyelectrolyte complexes with anionic macromolecules. LMWH
      (Low Molecular Weight Heparin) is an anionic polysaccharide finding clinical
      application as an improved antithrombotic agent compared to Unfractionated
      Heparin (UFH). In this study we have employed N-sulfonato-N,O
      carboxymethylchitosan (SNOCC) as a potential intestinal absorption enhancer of
      LMWH, Reviparin. SNOCC was prepared at 3 different viscosity grades 20, 40 and 60
      cps and identified as SNOCC-20, SNOCC-40 and SNOCC-60, respectively. SNOCC
      materials were tested in vitro for their ability to decrease the Trans Epithelial
      Electrical Resistance (TEER) of Caco-2 cell monolayers. They were further tested
      as transport enhancers of hydrophilic compounds such as (14)C-mannitol, FITC
      Dextran (MW 4400 Da) and Reviparin (LMWH). Solutions of Reviparin, with or
      without SNOCC, were administered intraduodenally in vivo in rats and the
      absorption of the drug was assessed by measuring the Anti-Xa levels in rat
      plasma. In vitro studies showed that SNOCC materials were able to induce a
      concentration dependent decrease in the TEER of the Caco-2 monolayers. SNOCC-40
      and -60 were shown to decrease resistance more readily compared to the low
      viscosity SNOCC-20. (14)C-mannitol permeation data across intestinal epithelia
      were in agreement with the observed decrease in TEER; the higher viscosity SNOCC
      60 was the most effective demonstrating a 51-fold enhancement of the permeation
      of the radiolabeled marker. Studies with both FITC-Dextran and Reviparin
      demonstrated significantly increased permeation across Caco-2 cell monolayers
      when they were co-incubated at the apical side of the monolayer. Intestinal
      absorption of Reviparin in rats was increased when it was co-administered with
      SNOCC-40 and -60, in agreement with in vitro data. Anti-Xa levels were elevated
      to and above the antithrombotic levels and were sustained for at least 6 h,
      giving an 18.5-fold increase in the AUC of LMWH in rats. In conclusion, SNOCC-40
      and -60 have been shown to enhance both permeation and absorption of Reviparin
      across intestinal epithelia proving their potential as polymeric absorption
      enhancers.

PMID- 17184871
TI  - Hypertension in people with diabetes in sub-Saharan Africa: revealing the hidden
      face of the iceberg.
AB  - AIM: To evaluate the prevalence, awareness, treatment and control of hypertension
      in a diabetic population of Cameroon, a sub-Saharan African country. METHODS: Two
      hundreds and ten diabetic patients were consecutively enrolled over a 6-month
      period. A questionnaire was administered and physical examination done. The JNC
      VI and the latest WHO criteria were used to diagnose hypertension and diabetes,
      respectively, and control of hypertension was assessed against five different
      targets. RESULTS: Ninety-one percent of the participants had type 2 diabetes.
      Prevalence and awareness rates for hypertension were 66.7% (n=140) and 87.1%
      (n=122), respectively. Treatment rate among those aware of their hypertension
      status was 80.3% (n=98). Patients with hypertension were older, more
      overweight/obese and had a longer duration of diabetes. ACE inhibitors and
      diuretics were the two most used blood pressure (BP) lowering drugs. Following
      the ADA/JNC 7 goal, the control rate of hypertension among treated patients was
      10.2% (n=10). CONCLUSION: Diabetic patients in Cameroon exhibit a very high
      prevalence of hypertension and are about three times more affected than the
      general population. Awareness and treatment rates are high, but the control rate
      is very low. Large scale studies with intervention component are urgently
      required.

PMID- 17184872
TI  - Effect of soil moisture dynamics on dense nonaqueous phase liquid (DNAPL) spill
      zone architecture in heterogeneous porous media.
AB  - The amount, location, and form of NAPL in contaminated vadose zones are
      controlled by the spatial distribution of water saturation and soil permeability,
      the NAPL spill scenario, water infiltration events, and vapor transport. To
      evaluate the effects of these processes, we used the three-phase flow simulator
      STOMP, which includes a new permeability-liquid saturation-capillary pressure (k
      S-P) constitutive model. This new constitutive model considers three NAPL forms:
      free, residual, and trapped. A 2-D vertical cross-section with five stratigraphic
      layers was assumed, and simulations were performed for seven cases. The
      conceptual model of the soil heterogeneity was based upon the stratigraphy at the
      Hanford carbon tetrachloride (CT) spill site. Some cases considered co-disposal
      of NAPL with large volumes of wastewater, as also occurred at the Hanford CT
      site. In these cases, the form and location of NAPL were most strongly influenced
      by high water discharge rates and NAPL evaporation to the atmosphere. In order to
      investigate the impact of heterogeneity, the hydraulic conductivity within the
      lower permeability layer was modeled as a realization of a random field having
      three different classes. For six extreme cases of 100 realizations, the CT mass
      that reached the water table varied by a factor of two, and was primarily
      controlled by the degree of lateral connectivity of the low conductivity class
      within the lowest permeability layer. The grid size at the top boundary had a
      dramatic impact on NAPL diffusive flux just after the spill event when the NAPL
      was present near the ground surface. NAPL evaporation with a fine grid spacing at
      the top boundary decreased CT mass that reached the water table by 74%, compared
      to the case with a coarse grid spacing, while barometric pumping had a marginal
      effect for the case of a continuous NAPL spill scenario considered in this work.
      For low water infiltration rate scenarios, the distribution of water content
      prior to a NAPL spill event decreased CT mass that reached the water table by 98%
      and had a significant impact on the formation of trapped NAPL. For all cases
      simulated, use of the new constitutive model that allows the formation of
      residual NAPL increased the amount of NAPL retained in the vadose zone. Density
      driven advective gas flow from the ground surface controlled vapor migration in
      strongly anisotropic layers, causing NAPL mass flux to the lower layer to be
      reduced. These simulations indicate that consideration of the formation of
      residual and trapped NAPLs and dynamic boundary conditions (e.g., areas, rates,
      and periods of different NAPL and water discharge and fluctuations of atmospheric
      pressure) in the context of full three-phase flow are needed, especially for NAPL
      spill events at the ground surface. In addition, NAPL evaporation, density-driven
      gas advection, and NAPL vertical movement enhanced by water flow must be
      considered in order to predict NAPL distribution and migration in the vadose
      zone.

PMID- 17184873
TI  - Factors influencing participation in cutaneous screening among individuals with a
      family history of melanoma.
AB  - BACKGROUND: Targeting higher risk individuals, such as melanoma patients' first
      degree relatives, may be more efficient than mass skin cancer screening.
      OBJECTIVE: Our aim was to examine prevalence and predictors of total cutaneous
      examination in first-degree relatives. METHODS: Ninety-five first-degree
      relatives completed questionnaires assessing demographic and risk
      characteristics, perceived risk, perceived severity, self-efficacy, response
      efficacy, and total skin examination. Fourteen months later, first-degree
      relatives were asked if they had obtained a total skin examination during follow
      up. RESULTS: At baseline, 47% reported at least one total cutaneous examination
      and 27% had a health care provider recommendation for total skin examination. At
      follow-up, 37% had obtained a total skin examination. Baseline and follow-up
      total cutaneous examination was associated with more risk factors, higher
      education, provider recommendation, and greater perceived risk and severity. In
      multivariate analyses, provider recommendation and college education predicted
      follow-up total skin examination. LIMITATIONS: Data were self reported.
      Knowledge, health-care access, and follow-up provider recommendation were not
      assessed. CONCLUSION: Physicians and other providers may be influential in
      promoting total cutaneous examination in first-degree relatives.

PMID- 17184875
TI  - Anetoderma associated with primary antiphospholipid syndrome.
AB  - We report the case of a 34-year-old white man with a 7-year history of nodules on
      the face, neck, upper torso, and arms which evolved to anetodermic lesions. After
      onset of these lesions, deep vein thrombosis developed in the patient's right arm
      and leg in association with circulating antiphospholipid antibodies.

PMID- 17184874
TI  - Imiquimod as an antiaging agent.
AB  - BACKGROUND: Topical imiquimod therapy has proven to be effective for a variety of
      infectious, neoplastic, and inflammatory dermatologic diseases. Several published
      reports have validated the benefit of imiquimod therapy for actinic keratoses and
      superficial melanoma and nonmelanoma skin cancers. There is, however, limited
      evidence demonstrating the use of topical imiquimod application as an antiaging
      treatment. OBJECTIVES: We examined the effectiveness of imiquimod 5% cream in the
      treatment of photoaging by evaluating pretreatment and posttreatment biopsy
      specimens and documenting the histologic changes. METHODS: This study represents
      an extension of an earlier project in our department in which patients with
      biopsy-proven lesions of lentigo maligna (LM) were recruited from a university
      dermatology service, a hospital, and referrals from private practitioners for an
      open-labeled efficacy trial with daily topical application of 5% imiquimod for 3
      months. Biopsy of clinically affected skin was carried out on all patients before
      and after treatment. Using a semiquantitative method, biopsy specimens were
      analyzed for changes in the dermal collagen table (solar elastosis vs papillary
      dermal fibroplasia). Additional parameters analyzed included epidermal changes
      (atrophy vs acanthosis, melanin content, and hypergranulosis) and inflammatory
      effects (epidermal and dermal cell populations along with presence of pigment
      incontinence). Variables were compared using paired Wilcoxan rank sums. RESULTS:
      Of 26 evaluable patients who completed 3 months of daily application, 24 (>92.3%)
      showed a significant increase in papillary dermal fibroplasia (P < .0001) with
      associated reduction in solar elastosis (P = .0036). Other noteworthy findings
      were restoration of normal epidermal thickness (P = .0073) and melanization (P <
      .0001). LIMITATIONS: This study only evaluates the effect of imiquimod in the
      lesional skin of LM. It is not known whether the results are applicable to
      nonlesional, photoaged skin. CONCLUSION: Topical imiquimod appears to induce
      reparative changes to the epidermis and the dermal collagen table in chronically
      sun-damaged skin associated with LM, indicating its potential use as an antiaging
      treatment. These findings need to be confirmed in photodamaged skin not
      associated with LM.

PMID- 17184876
TI  - Epidermal growth factor receptor inhibitors: a new era of drug reactions in a new
      era of cancer therapy.

PMID- 17184877
TI  - Psychologic distress in polymorphous light eruption and its relationship to
      patients' beliefs about their condition.
AB  - BACKGROUND: Skin disease can cause psychologic difficulties, but information is
      lacking on the emotional impact of the common photosensitivity condition,
      polymorphous light eruption (PMLE). OBJECTIVE: We sought to examine the emotional
      impact of PMLE, and its relationships with patients' beliefs about their PMLE and
      health-related variables. METHODS: Patients with PMLE who had attended a hospital
      dermatology department were mailed the Illness Perception Questionnaire-Revised
      during the summers of 2002 to 2004. RESULTS: Questionnaires were returned by 150
      of 302 patients. Emotional distress attributable to PMLE was found in more than
      40% of individuals. The emotional impact of PMLE was principally predicted by
      patients' beliefs about their condition (>50% of the variance), particularly
      regarding its consequences, whereas health-related variables played a lesser
      role. Women associated more severe consequences with their PMLE (z = -2.27, P =
      .02) and were more emotionally distressed (z = -2.17, P = .03) than men.
      LIMITATIONS: Hospital-based patients with PMLE may not be representative of the
      community. CONCLUSIONS: Psychologic factors should receive greater attention in
      PMLE management.

PMID- 17184878
TI  - Differential expression of decorin in localized scleroderma following ultraviolet
      A1 irradiation.
AB  - Patients with localized scleroderma underwent an 8-week course of ultraviolet A1
      phototherapy. At baseline, decorin levels of lesional skin were significantly
      lower than those of nonlesional skin and healthy control subjects. After
      ultraviolet A1 phototherapy, decorin levels of lesional skin were significantly
      higher than baseline. Decorin may be of significance in the pathogenesis of
      localized scleroderma.

PMID- 17184879
TI  - Open-label pilot study of combination therapy with rosiglitazone and bexarotene
      in the treatment of cutaneous T-cell lymphoma.
AB  - Four patients with stable or progressive cutaneous T-cell lymphoma treated with
      oral bexarotene received oral rosiglitazone. After 16 weeks of combination
      therapy, skin score decreased in two patients. Pruritus was alleviated in 3 of 4
      patients, whereas quality of life was unchanged. Adverse events included
      hyperlipidemia, anemia, neutropenia, and lymphopenia.

PMID- 17184880
TI  - Drive for thinness score is a proxy indicator of energy deficiency in exercising
      women.
AB  - The purpose of this study was to determine the association between drive for
      thinness (DT) and adaptations to energy deficiency in exercising women. This
      observational study evaluated psychometric and metabolic factors in sedentary
      (n=9, 27.9+/-2.0 yr) and exercising women (n=43, 24.0+/-1.1 yr). Volunteers were
      retrospectively grouped according to exercise status (sedentary or exercising)
      and a DT score of normal (sedentary or exercising) or high (exercising only).
      Resting energy expenditure (REE) and metabolic hormones (triiodothyronine, (TT3),
      ghrelin, leptin, insulin) were measured repeatedly over a 2-3 month period. The
      DT subscale successfully discriminated the groups based on energy status.
      Although the groups did not differ in body weight, the high DT group exhibited
      adaptations to chronic energy deficiency, including a REE below 90% of their
      predicted REE (86+/-3.0%), significantly lower TT3 levels and significantly
      higher ghrelin levels than the normal DT groups. Since energy deficiency plays a
      causal role in the Female Athlete Triad, DT may serve as a proxy indicator of
      underlying energy deficiency and may be useful for identifying individuals at
      risk for Triad disorders prior to the development of serious clinical sequelae.

PMID- 17184882
TI  - Glucocorticoid receptor variant and risk of dementia and white matter lesions.
AB  - OBJECTIVE: Elevated glucocorticoid levels are associated with dementia. A
      glucocorticoid receptor gene variant (ER22/23EK) is related to relative
      glucocorticoid resistance. We investigated whether the ER22/23EK allele is
      associated with dementia and structural brain abnormalities. METHODS: This study
      was performed in two prospective population-based cohort studies among elderly.
      The first study included 6034 participants who were screened for dementia (mean
      follow-up 5.8 years). The second study included 1011 elderly subjects with an MRI
      at baseline and follow-up. The ER22/23EK allele was assessed for association with
      dementia, cognitive function and white matter lesions. RESULTS: The ER22/23EK
      allele was associated with a decreased risk of dementia. Among non-demented
      participants, ER22/23EK-carriers had a better performance on psychomotor speed
      tests than non-carriers. No differences were found in memory function between
      genotypes. In addition, both presence and progression of white matter lesions was
      lower in ER22/23EK-carriers. No association was found with brain atrophy on MRI.
      CONCLUSIONS: Our findings suggest a protective effect of the ER22/23EK allele on
      the risk of dementia and white matter lesions.

PMID- 17184881
TI  - I. Longitudinal changes in aging brain function.
AB  - Changes in brain activity over time were evaluated in a group of older adults in
      the Baltimore Longitudinal Study of Aging who maintained good physical and
      cognitive health. Participants underwent PET scans during rest and delayed verbal
      and figural recognition memory performance at year 1 baseline and at year 9.
      While memory performance remained stable over the 8 years, longitudinal changes
      in regional cerebral blood flow were observed within each scan condition. Further
      analyses revealed distinctive patterns of change related specifically to verbal
      or figural recognition, as well as longitudinal changes common to all scan
      conditions. These findings demonstrate that the older brain undergoes functional
      reorganization with increasing age in healthy, cognitively stable individuals. In
      view of the stable memory performance, the task-dependent results suggest that
      age-related changes in brain activity help maintain cognitive function with
      advancing age.

PMID- 17184883
TI  - NADH hyperoxidation correlates with enhanced susceptibility of aged rats to
      hypoxia.
AB  - Aging increases mitochondrial dysfunction and susceptibility to hypoxia. Previous
      reports have indicated an association between post-hypoxic hyperoxidation of
      intra-mitochondrial enzymes and delayed neuronal injury. Therefore we
      investigated the relationship between NADH fluorescence and neuronal function
      during and after hypoxia across the lifespan. Hippocampal slices were prepared
      from adult (1 to >22 months) F344 rats. NADH fluorescence, extracellular voltage
      and tissue PO(2) were recorded from the CA1 region during hypoxia (95% N(2)) of
      various lengths following onset of hypoxic spreading depression (hsd). Slices
      from younger rats recovered evoked neuronal responses to a greater degree and
      exhibited less hyperoxidation after a hypoxic episode, than slices from older
      rats. However, the use of Ca(2+) free-media in slices from >22 month old rats
      improved recovery and delayed NADH hyperoxidation (2.5 min hypoxia after hsd).
      Post-hypoxic decrease of NADH fluorescence (hyperoxidation) was age dependent and
      correlated with decreased neuronal recovery. Slices exposed to repeated hypoxic
      episodes yielded data suggesting depletion of the NAD(+) pool, which may have
      contributed to the deterioration of neuronal function.

PMID- 17184885
TI  - Synthesis and evaluation of novel 1-(1H-1,2,4-triazol-1-yl)-2-(2,4
      difluorophenyl)-3-[(4-substitutedphenyl)-piperazin-1-yl]-propan-2-ols as
      antifungal agents.
AB  - A series of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4
      substitutedphenyl)-piperazin-1-yl]-propan-2-ols have been designed and
      synthesized on the basis of the structure-activity relationships and antimycotic
      mechanism of azole antifungal agents. Their structures were confirmed by
      elemental analysis, IR, MS, (1)H NMR and (13)C NMR. Results of preliminary
      antifungal tests against six human pathogenic fungi (Candida albicans, Candida
      parapsilosis, Cryptococcus neoformans, Candida tropicalis, inherently fluconazole
      resistant Candida krusei, Candida glabrata) in vitro showed that all title
      compounds exhibited activity against fungi tested to some extent except against
      C. tropicalis. Compound 5b showed higher activity against C. albicans, C.
      parapsilosis and C. krusei than fluconazole, and its MIC values were determined
      to be 0.5microg/mL, 1microg/mL and 4microg/mL, respectively. Compound 5k showed
      higher activities against Torulopsis glabrata than fluconazole (with the MIC
      value of 2microg/mL). Compounds 5a, 5c, 5f, 5g, 5i exhibited higher activities
      against C. parapsilosis than fluconazole (with the MIC values of 2microg/mL,
      2microg/mL, 2microg/mL, 1microg/mL and 2microg/mL, respectively).

PMID- 17184884
TI  - Identification of novel short chain 4-substituted indoles as potent alphavbeta3
      antagonist using structure-based drug design.
AB  - The vitronectin receptor alpha(v)beta(3) has been identified as a promising
      potential target for the treatment of osteoporosis, diabetic retinopathy and
      cancer. We have recently reported 5-substituted indoles 3-[5-[2-(5,6,7,8
      tetrahydro[1,8]naphthyridin-2-yl)ethoxy]indol-1-yl]-3-(3-pyridyl)propionic acid 3
      and 3-[5-[2-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)ethoxy]indol-1-yl]-3-(3,4
      methylenedioxyphenyl)propionic acid 4, as an original series of potent
      alpha(v)beta(3) antagonists with subnanomolar activity. Ligand-protein docking
      analyses have been performed to generate binding models of three different
      chemical classes of known alpha(v)beta(3) antagonists with alpha(v)beta(3).
      Results of this docking study suggested that indoles bearing the basic
      tetrahydronaphthyridine group at position 4 can easily adopt the correct binding
      conformation and should be as potent as our current 5-substituted indole leads 3
      and 4. This hypothesis was nicely demonstrated by the synthesis of a series of
      1,4-disubstituted indoles through a tandem of reactions involving: (i) the N
      alkylation of indoles 15 and 22 with propargyl esters and cesium fluoride, and
      (ii) a Heck coupling reaction between 4-bromoindole and 7-vinyl-3,4-dihydro-2H
      [1,8]naphthyridine-1-carboxylic acid tert-butyl ester 12, or (iii) a reductive
      amination involving the N-substituted-4-aminoindole 23 and the BOC-protected
      tetrahydro[1,8]naphthyridine aldehyde 13. Among the compounds assayed, 3-(3
      pyridyl)-3-[4-[2-(5,6,7,8-tetrahydro[1,8]naphthyridin-2-yl)ethyl]indol-1
      yl]propionic acid 21 showed the most promising activity on alpha(v)beta(3)
      (IC(50)=0.5 nM), and was found to have the same potency as our current leads 3
      and 4, while maintaining selectivity over alpha(IIb)beta(IIIa). Moreover, based
      on the reasonable apparent permeability coefficient in an in vitro CACO-2 cell
      monolayer assay (P(app) apical/basolateral=2.2 x 10(-6)cm/s, P(app)
      basolateral/apical=2.5 x 10(-6)cm/s), compound 21 is expected to be absorbed
      through the intestine in human. Thus, 1,4-disubstituted indole 21 represents a
      new lead for this novel class of conformationally restricted alpha(v)beta(3)
      antagonists. Additionally, this study validates the pharmacophore model
      previously postulated and provides an improved basis for further structure-based
      drug design in the field of alpha(v)beta(3).

PMID- 17184886
TI  - Perception of hospital learning environment: a survey of Hong Kong nursing
      students.
AB  - The last two decades have seen widespread changes to nurse education but the
      clinical field remains an essential and invaluable resource in preparing students
      for the reality of their professional role, supporting the integration of theory
      and practice, and linking the 'knowing what' to do with the 'knowing how' to
      deliver care. The clinical learning environment represents a vital element of
      nurse education that needs to be measurable and warrants further investigation.
      This survey study examined Hong Kong nursing students' perception of the social
      climate of the clinical learning environment. Participants were invited to
      complete the two versions, the Actual and Preferred Forms, of the Clinical
      Learning Environment Inventory following the completion of their clinical field
      placement. Two hundred eighty one Actual Forms and 243 Preferred Forms returned.
      SPPS version 11 was employed to analyse data with descriptive and inferential
      statistics. It was found that there were significant differences between
      students' perceptions of the actual clinical learning environment and the ideal
      clinical learning environment they desired. The study highlights the need for a
      supportive clinical learning environment which is of paramount importance for
      students in clinical practice.

PMID- 17184887
TI  - Behavioral activation treatments of depression: a meta-analysis.
AB  - Activity scheduling is a behavioral treatment of depression in which patients
      learn to monitor their mood and daily activities, and how to increase the number
      of pleasant activities and to increase positive interactions with their
      environment. We conducted a meta-analysis of randomized effect studies of
      activity scheduling. Sixteen studies with 780 subjects were included. The pooled
      effect size indicating the difference between intervention and control conditions
      at post-test was 0.87 (95% CI: 0.60 - 1.15). This is a large effect.
      Heterogeneity was low in all analyses. The comparisons with other psychological
      treatments at post-test resulted in a non-significant pooled effect size of 0.13
      in favor of activity scheduling. In ten studies activity scheduling was compared
      to cognitive therapy, and the pooled effect size indicating the difference
      between these two types of treatment was 0.02. The changes from post-test to
      follow-up for activity scheduling were non-significant, indicating that the
      benefits of the treatments were retained at follow-up. The differences between
      activity scheduling and cognitive therapy at follow-up were also non-significant.
      Activity scheduling is an attractive treatment for depression, not only because
      it is relatively uncomplicated, time-efficient and does not require complex
      skills from patients or therapist, but also because this meta-analysis found
      clear indications that it is effective.

PMID- 17184889
TI  - The n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia.
AB  - The dopamine hypothesis of schizophrenia has been the most influential since the
      1970s. Normally, the prefrontal dopamine system suppressively controls the limbic
      dopamine system. Since the activities of prefrontal dopaminergic neurons are
      reduced in schizophrenia, the suppressive effect of the prefrontal area on the
      limbic system is reduced, and activities of the limbic dopamine system are
      enhanced. Reduced activities of the prefrontal dopamine system contribute to
      negative symptoms and cognitive disorders, and increased activities of the limbic
      dopamine system induce positive symptoms. While the dopamine hypothesis explains
      the relationship between dopamine kinetics and psychiatric symptoms in
      schizophrenia, it is not a direct explanation of its etiology. The cause of the
      abnormal activities of dopaminergic neurons in schizophrenia and its resultant
      symptoms are unknown. Since the late 1980s, it has been revealed that the n-3
      fatty acid concentration is reduced in the plasma and erythrocyte membranes of
      schizophrenic patients and that the administration of n-3 fatty acids may be
      effective for the treatment of schizophrenia. Whether or not n-3 fatty acid
      deficiency plays a direct role in schizophrenia etiology, and the mechanisms
      underlying their therapeutic effect have yet to be clarified. Recently, the
      dopamine hypothesis and n-3 fatty acid hypothesis have been suggested to
      represent different aspects of the same pathology of schizophrenia. In
      schizophrenia, the brain concentrations of certain n-3 fatty acids are decreased.
      In rodents, n-3 fatty acid deficiency has been shown to cause decreases in
      dopamine concentration, number of vesicles and D2 receptors at prefrontal
      presynaptic terminals. The following minireview provides a summary of findings
      from n-3 fatty acid deficient animal models and their relevance to schizophrenia
      pathology is discussed.

PMID- 17184891
TI  - Sub-chronic exposure of adult male rats to diphenyl ditelluride did not affect
      the development of their progeny.
AB  - The present study was undertaken to evaluate the toxicity of diphenyl ditelluride
      [(PhTe)(2)] exposure on the progeny of Wistar male rats. Male rats were exposed
      to (PhTe)(2) subcutaneously for 4 weeks (wk) at the dose of 0.006 mg/kg and 8-wk
      at the dose of 0.003 mg/kg, prior to mating with unexposed females. The body and
      sex organ weights of male rats were not affected in both 4- and 8-wk (PhTe)(2)
      exposed groups. The gravid uterus weight and the body weight gain (overall or
      corrected) during the pregnancy were not statistically different to those
      obtained from females mated with control males. The number of implantation sites,
      resorptions and live and dead fetuses were not affected by male exposure to
      (PhTe)(2). Fetal body weight and crown-rump length were not affected, as well.
      Examination of the fetuses from both exposed groups for external and skeletal
      changes did not reveal any male-mediated effect of (PhTe)(2). The current study
      indicated that (PhTe)(2) given sub-chronically (4- or 8-wk) to male rats had no
      adverse effects on their progeny.

PMID- 17184890
TI  - Kinetic and cardiovascular effects of acute topiramate dosing among non-treatment
      seeking, methamphetamine-dependent individuals.
AB  - Previously, we have shown that orally administered topiramate, a sulfamate
      substituted fructopyranose derivative, appears to accentuate rather than diminish
      some aspects of methamphetamine-induced positive subjective mood and cognitive
      performance. One possible mechanism by which this might occur would be for
      topiramate to increase plasma methamphetamine level. Such an effect also would be
      expected to enhance methamphetamine-induced hemodynamic response. We, therefore,
      studied -- in the same experiment from which the previous findings originated --
      the effects of topiramate on the kinetic profile and hemodynamic response to
      methamphetamine. In a 27-day inpatient study, 10 methamphetamine-dependent
      individuals participated in a double-blind, placebo-controlled, cross-over
      design, with oral doses of topiramate (0, 100, and 200 mg) administered as a
      pretreatment before intravenous doses of methamphetamine (0, 15, and 30 mg). The
      3x3 factorial combination of topiramate and methamphetamine resulted in a
      sequence of the nine treatments administered to each subject in an order
      determined by a 9x9 Latin Square design. Methamphetamine alone was associated
      with prototypical increases in hemodynamic response that were not altered in the
      presence of topiramate. While there was no significant kinetic interaction
      between topiramate and methamphetamine, there was a non-significant trend for
      topiramate to increase plasma methamphetamine level. No significant adverse
      events were reported. The combination of topiramate and methamphetamine at
      pharmacologically relevant doses appears to be safe. Larger laboratory studies
      with chronic dosing regimens are needed to establish whether or not there is a
      kinetic interaction between topiramate and methamphetamine.

PMID- 17184892
TI  - Deconjugation of N-glucuronide conjugated metabolites with hydrazine hydrate-
      biomarkers for exposure to the food-borne carcinogen 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP).
AB  - The metabolism of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      (PhIP) has been investigated in rabbit liver S9. Two phase I metabolites, N(2)-OH
      PhIP and 4'-OH-PhIP were identified based on UV and mass spectra and co-elution
      with reference standards. Fortification of the incubation with UDGPA resulted in
      a complete glucuronidation of PhIP and N(2)-OH-PhIP, while 4'-OH-PhIP was only
      partly glucuronidated. Also, the PhIP metabolite 5-OH-PhIP was completely
      glucuronidated by rabbit liver S9, while 5-OH-PhIP was a poor substrate for CYP
      mediated hydroxylation. The glucuronic acid conjugates of PhIP metabolites were
      unsusceptible to treatment with beta-glucuronidase indicating that these are N
      glucuronides. Treatment of the conjugates with hydrazine hydrate, however,
      resulted in complete hydrolysis of the glucuronic acid conjugates as well as in
      reduction to the parent amine of metabolites hydroxylated in the exocyclic amino
      group. Urine was collected from a male volunteer following consumption of fried
      chicken. Treatment of the urine with beta-glucuronidase/sulfatase resulted in
      release of 4'-OH-PhIP, while treatment with hydrazine hydrate in addition
      resulted in release of substantial amounts of PhIP and 5-OH-PhIP. The data show
      that hydrazine hydrate can hydrolyse N-glucuronides of metabolites of PhIP,
      glucuronides that are unsusceptible to enzymatic hydrolysis. In addition the data
      indicate that humans metabolise a large fraction of ingested PhIP to genotoxic
      metabolites. The chemical hydrolysis of glucuronide conjugates of PhIP
      metabolites with hydrazine hydrate observed in this study may also be a useful
      approach in the development of biomarkers for exposure and effect of other
      xenobiotics.

PMID- 17184893
TI  - Are 4-hydroxy-2(E)-nonenal derived mercapturic acids and (1)H NMR metabonomics
      potential biomarkers of chemically induced oxidative stress in the kidney?
AB  - Various markers derived from radical-mediated oxidative damage to cellular
      macromolecules have been proposed as tools for the detection of alterations in
      redox status, but there is strong debate as to which may be the most sensitive
      and reliable indicator of oxidative stress conditions. This study was aimed to
      investigate the use of mercapturic acids derived from conjugation of the lipid
      peroxidation product 4-hydroxy-2(E)-nonenal (HNE) with glutathione and (1)H NMR
      metabonomics in two rodent models of oxidative kidney damage. Treatment of rats
      with FeNTA resulted in a marked increase in the concentrations of 4-hydroxy-2(E)
      nonenal derived mercapturic acids in plasma and kidney within 5h. 1,4
      dihydroxynonenal mercapturic acid (DHN-MA) remained elevated 24h after compound
      administration, while other markers returned to control levels, suggesting that
      DHN-MA may present a more stable indicator of lipid peroxidation. However,
      significant changes were only evident in the presence of severe nephrotoxicity,
      indicating that HNE-derived mercapturic acids were less sensitive than
      nonspecific markers of renal injury. In contrast to FeNTA, continuous
      administration of potassium bromate for 2 weeks had no effect on the
      concentrations of DHN-MA or 4-hydroxyononenal-3-yl-mercapturic acid in kidney,
      plasma or urine of treated animals, although a dose-dependent increase in 8-oxo
      7,8-dihydro-2'deoxyguanosine was observed in kidney DNA in the absence of
      nephrotoxicity. These data suggest that markers of lipid peroxidation may not be
      suitable to detect alterations in redox status induced by potassium bromate at
      doses known to cause tumors after chronic treatment. Alterations in urine (1)H
      NMR spectra were detected in both models but reflect nonspecific alterations as a
      result of impaired renal function rather than specific changes indicative of
      oxidative stress. In summary, it appears that - depending on the pathological
      circumstances and the chemical nature of the insult - different types of
      oxidative stress exist, and it is therefore not possible to define a universal
      marker of oxidative stress.

PMID- 17184896
TI  - Air way scope, a portable video-laryngoscope, for confirmation of tracheal
      intubation.

PMID- 17184895
TI  - Ketoprofen glucuronidation and bile excretion in carbon tetrachloride and alpha
      naphthylisothiocyanate induced hepatic injury rats.
AB  - A pharmacokinetic study was carried out in rats to investigate the effects of
      experimental hepatic injury on the liver glucuronidation and bile excretion of
      ketoprofen (KP) and its glucuronides (KPGs). In vivo, KP (20mg/kg b.w.) was
      intravenously administered to carbon tetrachloride (CCl(4)) or alpha
      naphthylisothiocyanate (ANIT) induced hepatic injury male rats. Concentrations of
      KP and its glucuronides (S-KPG and R-KPG) in plasma and bile were determined by
      RP-HPLC. It was observed that there was significant difference in the
      accumulative bile excretion of KPGs between the CCl(4) intoxicated rats and the
      normal rats (54+/-18.3% versus 90+/-6.9%), while it was extremely inhibited in
      ANIT intoxicated rats (2.0+/-3.1% versus 90+/-6.9%). As the result of reduction
      of KPGs excreted in bile, the area under the curve (AUC((0-infinity))) of KP and
      KPGs were higher in blood in CCl(4) and ANIT hepatic injury rats than those of
      the normal rats. Specifically, ANIT caused approximately 10-fold elevation of
      AUC((0-infinity)) of plasma S-KPG. In microsomal incubations experiment, the
      glucuronyltransferase activity was impaired in CCl(4) and ANIT intoxicated rats.
      It suggested that the glucuronyltransferase activity was impaired in CCl(4) and
      ANIT intoxicated rats, while the bile excretion function was suppressed extremely
      in ANIT intoxicated rats.

PMID- 17184894
TI  - Modulating effects of dietary fats on methylmercury toxicity and distribution in
      rats.
AB  - Fish consumption is the most important source of human exposure to methylmercury
      (MeHg). Since fish is also a rich source of n-3 polyunsaturated fatty acids, this
      study was conducted to examine the effects of dietary fats on MeHg-induced acute
      toxicity in rats. Weanling male Sprague Dawley rats were administered semi
      purified casein-based isocaloric diet containing soy oil, seal oil,
      docosahexaenoic acid (DHA), fish oil, or lard for 28 days. Rats were then gavaged
      with 0, 1, or 3 mg MeHg/kg body weight (BW) per day and fed the same diet for 14
      consecutive days. On 43rd day of the experiment, rats were sacrificed and blood
      samples were collected and analyzed for hematology. Liver and spleen were
      removed, fixed, and examined for pathological changes. Blood, feces, liver, and
      brain were analyzed for total mercury and/or MeHg contents. Serum samples were
      analyzed for clinical markers of hepatic injury and immunoglobulin. Total mercury
      contents in all tissues measured increased with dose. Mercury excretion in feces
      increased with dose and duration of MeHg treatment. Both diets and MeHg showed
      significant effects and interacted significantly on many of the toxicological
      endpoints measured. Many of the effects of MeHg were diet-dependent. For example,
      in the rats fed the lard diet, 3mg MeHg/kg BW significantly increased relative
      liver and spleen weight as compared with vehicle control; whereas in rats fed the
      fish oil, soy oil, seal oil, or DHA, this effect of MeHg was less obvious or
      absent, suggesting a protective effect of these diets. MeHg at 3mg/kg BW
      significantly decreased serum albumin level in all except DHA dietary groups,
      implying a protection by the DHA diet on this parameter. Only in the lard dietary
      group, did 3mg MeHg/kg BW significantly increase serum bilirubin level,
      indicating an enhancing effect of this diet on MeHg toxicity. MeHg suppressed the
      adaptive immune system and stimulated the innate immune system in rats in a diet
      dependent fashion. The seal oil diet provided more resistance, while the fish oil
      diet rendered greater sensitivity to these effects of MeHg on the immune system.
      These results imply significant modulating effects of dietary fats on MeHg
      toxicity which may translate into more severe or protective clinical outcomes.
      Therefore, dietary fats are important factors to be considered in the risk
      assessment of MeHg exposure.

PMID- 17184897
TI  - Effects of feeding time and organic loading in an anaerobic sequencing batch
      biofilm reactor (ASBBR) treating diluted whey.
AB  - An investigation was carried out on the performance of an anaerobic sequencing
      batch biofilm reactor (ASBBR) treating diluted cheese whey when submitted to
      different feed strategies and volumetric organic loads (VOL). Polyurethane foam
      cubes were used as support for biomass immobilization and stirring was provided
      by helix impellers. The reactor with a working volume of 3 L treated 2 L of
      wastewater in 8-h cycles at 500 rpm and 30 degrees C. The organic loads applied
      were 2, 4, 8 and 12 g COD L(-1) d(-1), obtained by increasing the feed
      concentration. Alkalinity was supplemented at a ratio of 50% NaHCO(3)/COD. For
      each organic load applied three feed strategies were tested: (a) batch operation
      with 8-h cycle; (b) 2-h fed-batch operation followed by 6-h batch; and (c) 4-h
      fed-batch followed by 4-h batch. The 2-h fed-batch operation followed by 6-h
      batch presented the best results for the organic loads of 2 and 4 g COD L(-1) d(
      1), whereas the 4-h fed-batch operation followed by 4-h batch presented results
      slightly inferior for the same organic loads and the best results at organic
      loads of 8 and 12 g COD L(-1) d(-1). The concentration of total volatile acids
      varied with fill time. For the higher fill times maximum concentrations were
      obtained at the end of the cycle. Moreover, no significant difference was
      detected in the maximum concentration of total volatile acids for any of the
      investigated conditions. However, the maximum values of propionic acid tended to
      decrease with increasing fill time considering the same organic load.
      Microbiological analyses revealed the presence of Methanosaeta-like structures
      and methanogenic hydrogenotrophic-like fluorescent bacilli. No Methanosarcina
      like structures were observed in the samples.

PMID- 17184898
TI  - Laparoscopic radical prostatectomy in men older than 70 years of age with
      localized prostate cancer: comparison of morbidity, reconvalescence, and short
      term clinical outcomes between younger and older men.
AB  - OBJECTIVES: To analyze the safety and efficacy of extraperitoneal laparoscopic
      radical prostatectomy (eL-RPE) in elderly versus younger men with localized
      prostate cancer. METHODS: Patients undergoing eL-RPE were retrospectively
      subdivided into group eL-RPE1 (72 men aged 71 yr and older) and group eL-RPE2
      (132 men aged 59 yr and younger). Group eL-RPE1 was compared with a group of 70
      contemporary, comparable patients aged 71 yr and older undergoing open retropubic
      radical prostatectomy (group OPEN-RPE). RESULTS: Compared with group eL-RPE2,
      patients of group eL-RPE1 had a higher pathologic stage (45% vs. 32% stage pT3 or
      greater, p<0.001) and higher Gleason score (median 7 vs. 6, p<0.001). Prostate
      specific antigen recurrence was significantly worse compared with age-matched
      controls for younger patients with high-stage or high-grade lesions (p<0.001).
      Importantly operative time, analgesic requirements, hospital stay, convalescence,
      and complication rates were comparable. Urinary continence rate was significantly
      better in group eL-RPE2 at 6 mo (67% vs. 91%, respectively, p<0.001). Group eL
      RPE1 and group OPEN-RPE patients had statistically similar pathologic stage and
      Gleason score (each p>0.05), similar operative time (p=0.12), but less blood loss
      (p<0.001), shorter hospital stay (p<0.001), and more rapid convalescence
      (p<0.001) occurred in eL-RPE1. CONCLUSIONS: eL-RPE is feasible and efficacious
      even in elderly patients with unfavorable, large-volume disease. eL-RPE offers
      the advantages of decreased blood loss, shorter hospital stay, and more rapid
      recovery over OPEN-RPE. However, the elderly patient must be informed
      preoperatively about the observed higher incontinence rate.

PMID- 17184899
TI  - Input-output relationship in galvanotactic response of Dictyostelium cells.
AB  - Under a direct current electric field, Dictyostelium cells exhibit migration
      towards the cathode. To determine the input-output relationship of the cell's
      galvanotactic response, we developed an experimental instrument in which electric
      signals applied to the cells are highly reproducible and the motile response are
      analyzed quantitatively. With no electric field, the cells moved randomly in all
      directions. Upon applying an electric field, cell migration speeds became about
      1.3 times faster than those in the absence of an electric field. Such kinetic
      effects of electric fields on the migration were observed for cells stimulated
      between 0.25 and 10 V/cm of the field strength. The directions of cell migrations
      were biased toward the cathode in a positive manner with field strength, showing
      galvanotactic response in a dose-dependent manner. Quantitative analysis of the
      relationship between field strengths and directional movements revealed that the
      biased movements of the cells depend on the square of electric field strength,
      which can be described by one simple phenomenological equation. The threshold
      strength for the galvanotaxis was between 0.25 and 1 V/cm. Galvanotactic
      efficiency reached to half-maximum at 2.6 V/cm, which corresponds to an
      approximate 8 mV voltage difference between the cathode and anode direction of 10
      microm wide, round cells. Based on these results, possible mechanisms of
      galvanotaxis in Dictyostelium cells were discussed. This development of
      experimental system, together with its good microscopic accessibility for
      intracellular signaling molecules, makes Dictyostelium cells attractive as a
      model organism for elucidating stochastic processes in the signaling systems
      responsible for cell motility and its regulations.

PMID- 17184900
TI  - Tropomyosin as a regulator of the sliding movement of actin filaments.
AB  - We examined the capacity of tropomyosin molecules regulating the sliding movement
      of actin filaments on myosin molecules in the presence of ATP molecules to be
      hydrolyzed. For this objective, we prepared tropomyosin molecules modified to be
      a little bit stiffer compared to the intact ones by applying a fixed cross-linker
      between a pair of twisted tropomyosin monomers. The cross-linked tropomyosin
      molecules, when complexed with actin filaments, were found to inhibit the sliding
      movement of the filaments on myosin molecules even in the absence of calcium
      regulated troponin molecules. It is then suggested that the mechanical
      flexibility of tropomyosin molecules may be instrumental to actualizing the
      proper functional regulation of the sliding movement of actin filaments.

PMID- 17184901
TI  - Therapeutic rewiring by means of desynchronizing brain stimulation.
AB  - We study possible anti-kindling effects of the standard high-frequency deep brain
      stimulation (HFDBS) and of a desynchronizing multisite coordinated reset
      stimulation (MCRS) theoretically in a mathematical model of the subthalamic
      nucleus (STN). The latter is an effective target for deep brain stimulation (DBS)
      in patients suffering from Parkinson's disease (PD). Depending on the structures
      being activated, electrical pulses may have excitatory and/or inhibitory impact.
      According to our simulation results MCRS may achieve robust long-term anti
      kindling (i.e., curative) effects, irrespectively, of the ratio between
      excitatory and inhibitory impact. This means, that during MCRS the STN unlearns
      its pathologic synaptic connections and reestablishes a physiological level of
      connectivity. In contrast, HFDBS has anti-kindling effects only if its impact is
      predominantly excitatory. Our results are relevant for selecting appropriate
      locations for DBS electrodes. In fact, even with HFDBS we may expect anti
      kindling effects, provided the target is properly chosen.

PMID- 17184902
TI  - On the legacy of W.S. McCulloch.
AB  - In this paper, we review McCulloch's legacy, from his early work in
      neurophysiology, and its relationship to his philosophical quest for an
      'experimental epistemology' to his role in the cybernetics movement during the
      1940s and 1950s and his contributions to the development of computer science and
      communication theory. There are three parts in chronological sequence. First, the
      period up to his work at Yale University with Dusser de Barenne, where he
      concentrated on the experimental study of the functional organization of sensory
      cortex. Second, the time of his Psychiatric Chair at the University of Chicago
      and the organization of the Macy Foundation Conferences. To this period
      corresponds the genesis and publication of the most influential and quoted work
      by McCulloch and Pitts: A Logical Calculus of the Ideas Immanent in Neurons
      Activity. Third, the period of his research activity at the Massachussetts
      Institute of Technology where he, Lettvin, Maturana and Pitts produced
      epochmaking papers on epistemological neurophysiology, the modelling of the
      reticular formation and other work with da Fonseca and Moreno-Diaz. We finally
      refer to the International Conference that took place in McCulloch's memory at
      the 25th anniversary of his death. Our main conclusion is that McCulloch's
      writings are still a source of inspiration from neurophysiology to artificial
      intelligence and robotics.

PMID- 17184903
TI  - Stochastic signal inputs for chemotactic response in Dictyostelium cells revealed
      by single molecule imaging techniques.
AB  - Chemotactic cells can exhibit extreme sensitivity to chemical gradients.
      Theoretical estimations of the signal inputs required for chemotaxis suggest that
      the response can be achieved under the strong influence of stochastic input noise
      generated by the receptors during the transmembrane signaling. This arises a
      fundamental question regarding the mechanisms for directional sensing: how do
      cells obtain reliable information regarding gradient direction by using
      stochastically operating receptors and the downstream molecules? To address this
      question, we have developed single molecule imaging techniques to visualize
      signaling molecules responsible for chemotaxis in living Dictyostelium cells,
      allowing us to monitor the stochastic signaling processes directly. Single
      molecule imaging of a chemoattractant bound to a receptor demonstrates that
      signal inputs fluctuate with time and space. Downstream signaling molecules, such
      as PTEN and a PH domain-containing protein that are constituent parts of
      chemotactic signaling system, can also be followed at single molecule level in
      living cells, illuminating the stochastic nature of chemotactic signaling
      processes. In this report, we start with a brief introduction of chemotactic
      response of the eukaryotic cells, followed by an explanation for single molecule
      imaging techniques, and finally discuss these applications to chemotactic
      signaling system of Dictyostelium cells.

PMID- 17184904
TI  - Genome-wide similarity search for transcription factors and their binding sites
      in a metal-reducing prokaryote Geobacter sulfurreducens.
AB  - The knowledge obtained from understanding individual elements involved in gene
      regulation is important for reconstructing gene regulatory networks, a key for
      understanding cellular behavior. To study gene regulatory interactions in a model
      microorganism, Geobacter sulfurreducens, which participates in metal reduction
      and energy harvesting, we investigated the presence of 59 known Escherichia coli
      transcription factors and predicted transcription regulatory sites in its genome.
      The supplementary material, available at
      http://www.geobacter.org/research/genomescan/, provides the results of similarity
      comparisons that identified regulatory proteins of G. sulfurreducens and the
      genome locations of the predicted regulatory sites, including the list of
      putative regulatory elements in the upstream regions of every predicted operon
      and singleton open reading frame. Regulatory sequence elements, predicted using
      genome similarity searches to matrices of established transcription regulatory
      elements from E. coli, provide an initial insight into regulation of genes and
      operons in G. sulfurreducens. The predicted regulatory elements were
      predominantly located in the upstream regions of operons and singleton open
      reading frames. The validity of the predictions was examined using a permutation
      approach. Sequence similarity searches indicate that E. coli transcription
      factors ArgR, CytR, DeoR, FlhCD (both FlhC and FlhD subunits), FruR, GalR, GlpR,
      H-NS, LacI, MetJ, PurR, TrpR, and Tus are likely missing from G. sulfurreducens.
      Phylogenetic analysis suggests that one HU subunit is present in G.
      sulfurreducens as compared to two subunits in E. coli, while each of the two E.
      coli IHF subunits, HimA and HimD, have two homologs in G. sulfurreducens. The
      closest homolog of E. coli RpoE in G. sulfurreducens may be more similar to FecI
      than to RpoE. These findings represent the first step in the understanding of the
      regulatory relationships in G. sulfurreducens on the genome scale.

PMID- 17184906
TI  - Functional connections between auditory cortical fields in humans revealed by
      Granger causality analysis of intra-cranial evoked potentials to sounds:
      comparison of two methods.
AB  - Knowledge of neural interactions amongst cortical sites is important for
      understanding higher brain function. We studied such interactions using Granger
      causality (GC) to analyze auditory event-related potentials (ERPs) recorded
      directly and simultaneously from two physiologically identified and functionally
      interconnected auditory areas of cerebral cortex in human neurosurgical patients.
      Two methods of GC analysis were used and the results compared. Both approaches
      involved adaptive autoregressive modeling but differed from each other in other
      ways. Results obtained by using the two methods also differed. Fewer false
      positive results were obtained using the method that suppressed the ERP non
      stationarity and that expressed the GC as the sum of model coefficients, which
      suggests that this is the more appropriate approach for analyzing ERPs recorded
      directly from the human cortex.

PMID- 17184905
TI  - Dynamic polymorphism of actin as activation mechanism for cell motility.
AB  - Actin filament dynamics are crucial in cell motility. Actin filaments, and their
      bundles, networks, and gels assemble and disassemble spontaneously according to
      thermodynamic rules. These dynamically changing structures of actin are harnessed
      for some of its functions in cells. The actin systems respond to external
      signals, forces, or environments by biasing the fluctuation of actin assembly
      structures. In this study, dynamic conformation of actin molecules was studied by
      monitoring conformational dynamics of actin molecules at the single molecule
      level in real time. Actin conformation spontaneously fluctuates between multiple
      conformational states. Regarding myosin motility, the dynamic equilibrium of
      actin conformation was interpreted as between states that activates and inhibits
      the motility. The binding of myosin to actin filaments activates myosin motility
      by shifting the conformational fluctuation of actin towards the state that
      activates the motility. Thus, the activation mechanism based on thermal
      fluctuation is suggested at molecular level as well as at cellular level.

PMID- 17184907
TI  - Analysis of ligand-dependent recruitment of coactivator peptides to RXRbeta in a
      time-resolved fluorescence resonance energy transfer assay.
AB  - Because RXR plays a significant role in nuclear receptor signaling as a common
      heterodimeric partner for TR, PPAR, RAR, VDR, LXR and others, the ability of
      RXRbeta ligand binding domain (LBD) to interact with coregulator peptides bearing
      LXXLL or other interaction motifs was investigated using time-resolved
      fluorescence resonance energy transfer (TR-FRET). The random phage display
      peptide D22 and peptides derived from PGC1alpha, SRC1-4, SRC2-3, PRIP/RAP250 and
      RIP140 yielded the highest TR-FRET signal with RXRbeta LBD in the presence of
      saturating 9-cis retinoic acid (9-cisRA). Several peptides including D22,
      PGC1alpha, SRC3-2, PRIP/RAP250 and SRC1-4 also formed a complex with RXRbeta LBD
      in the presence of all-trans retinoic acid (at-RA) and the fatty acids, phytanic
      acid (PA) and docosahexaenoic acid (DHA). Determination of the dose dependency
      (EC50) of these compounds to recruit D22 to RXRbeta LBD indicated that the rank
      order potency was 9-cisRA>PA>at-RA>DHA. The ligands 9-cisRA and at-RA yielded an
      overall higher fold-change in D22 recruitment to RXRbeta LBD suggesting that more
      RXRbeta LBD-D22 complex was formed in the presence of these ligands under the
      assay conditions tested. The statistical parameter Z' factor for 9-cisRA-induced
      recruitment of D22 to RXRbeta LBD was 0.6 after 2h incubation, indicating a
      robust methodology that could be applied to high throughput screening. These
      results demonstrate that RXRbeta occupied with the fatty acid ligands, DHA and
      PA, can recruit coactivator peptides in a ligand-dependent manner.

PMID- 17184908
TI  - Lexatumumab (TRAIL-receptor 2 mAb) induces expression of DR5 and promotes
      apoptosis in primary and metastatic renal cell carcinoma in a mouse orthotopic
      model.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis
      in a variety of tumorigenic and transformed cell lines but not in many normal
      cells. Hence, TRAIL-agonist compounds have the potential of being excellent
      cancer therapeutic agents with minimal cytotoxicity. Here, we examine the
      efficacy of the TRAIL-receptor 2 agonist, lexatumumab (Human Genome Sciences,
      Inc., Rockville, MD), and identify molecular pathways that differentiate between
      lexatumumab-sensitive and lexatumumab-resistance renal cancer cells. In an
      orthotopic metastatic mouse model, we first demonstrate that lexatumumab was
      effective in reducing the tumor burden of primary and metastatic lexatumumab
      sensitive xenografts. We demonstrate that lexatumumab-sensitive cells were
      capable of triggering both the extrinsic and the intrinsic apoptotic pathways as
      demonstrated by caspase 8 and caspase 9 activations, respectively, after
      treatment with lexatumumab. In addition, expression of c-FLIP(L) protein, an
      important regulator of TRAIL-induced apoptosis, decreased, while expression of
      the TRAIL-receptor 2, DR5, increased. This study serves as a pre-clinical model
      for using TRAIL-like therapies for patients with advanced RCC.

PMID- 17184910
TI  - Response surface optimization of electrochemical treatment of textile dye
      wastewater.
AB  - The electrochemical treatment of textile dye wastewater containing Levafix Blue
      CA, Levafix Red CA and Levafix Yellow CA reactive dyes was studied on iron
      electrodes in the presence of NaCl electrolyte in a batch electrochemical
      reactor. The wastewater was synthetically prepared in relatively high dye
      concentrations between 400mg/L and 2000mg/L. The electrochemical treatment of
      textile dye wastewater was optimized using response surface methodology (RSM),
      where current density and electrolyte concentration were to be minimized while
      dye removal and turbidity removal were maximized at 28 degrees C reaction
      temperature. Optimized conditions under specified cost driven constraints were
      obtained for the highest desirability at 6.7mA/cm(2), 5.9mA/cm(2) and 5.4mA/cm(2)
      current density and 3.1g/L, 2.5g/L and 2.8g/L NaCl concentration for Levafix Blue
      CA, Levafix Red CA and Levafix Yellow CA reactive textile dyes, respectively.

PMID- 17184911
TI  - Application of molybdenum and phosphate modified kaolin in electrochemical
      treatment of paper mill wastewater.
AB  - Pulp and paper mill wastewater is characterized by very high chemical oxygen
      demand (COD) values that inhibit the activity of microorganisms during biological
      oxidations. The electrochemical degradation of pulp and paper mill wastewater
      catalyzed by molybdenum and phosphate (Mo-P) modified kaolin with graphite as
      anode and cathode was investigated. The catalyst was characterized by XRD, XPS
      and SEM spectra and the effects of pH, metal ion and introduction of NaCl on the
      efficiency of the electrochemical degradation process were also studied. It was
      found out that the modified kaolin loaded with Fe(3+) had higher electrochemical
      catalytic activity in the electrochemical degradation of paper mill wastewater at
      pH 4. A 96% COD removal efficiency was obtained in 40min of electrochemical
      treatment of the wastewater at current density 30mAcm(-2). A possible mechanism
      for degradation of the mill wastewater constituents was also proposed.

PMID- 17184909
TI  - Synergistic apoptosis of MCF-7 breast cancer cells by 2-methoxyestradiol and
      bis(ethyl)norspermine.
AB  - 2-Methoxyestradiol (2ME) is an estradiol metabolite with anti-tumor and anti
      angiogenic properties. We studied the effect of 2ME on apoptosis of MCF-7 breast
      cancer cells and explored a combination therapy using 2ME and a polyamine
      analogue, bis(ethyl)norspermine (BE-3-3-3). Determination of viable cells on day
      4 of treatment with 2ME/BE-3-3-3 combinations showed synergistic effects by Chou
      Talalay analysis. APO-BRDU analysis showed that there was only 1.5+/-0.5%
      apoptosis at 200 nM 2ME and 3.7+/-1.7% in the presence of 2.5 microM BE-3-3-3.
      Combination of 200 nM 2ME and 2.5 microM BE-3-3-3 resulted in 52.2+/-2.6%
      apoptosis. Up to 90% of the cells underwent apoptosis in the presence of 1000 nM
      2ME and 2.5 microM BE-3-3-3. Combination treatments resulted in total disruption
      of microtubules and depletion of putrescine, spermidine and spermine. In
      addition, phosphorylation of Akt and nuclear localization of cyclin D1 were
      altered by 2ME/BE-3-3-3 combination. Our results suggest an important strategy to
      induce apoptosis of breast cancer cells, with potential applications in therapy.

PMID- 17184912
TI  - Coupling dynamic blow down and pool evaporation model for LNG.
AB  - Treating the dynamic effects of accidental discharges of liquefied natural gas
      (LNG) is important for realistic predictions of pool radius. Two phenomena have
      important influence on pool spread dynamics, time-varying discharge (blow down)
      and pool ignition. Time-varying discharge occurs because a punctured LNG tanker
      or storage tank drains with a decreasing liquid head and decreasing head-space
      pressure. Pool ignition increases the evaporation rate of a pool and consequently
      decreases the ultimate pool area. This paper describes an approach to treat these
      phenomena in a dynamic pool evaporation model. The pool evaporation model
      developed here has two separate regimes. Early in the spill, momentum forces
      dominate and the pool spreads independently of pool evaporation rate and the
      corresponding heat transfer rate. After the average pool depth drops below a
      minimum value, momentum forces are largely dissipated and the thin edges of the
      pool completely evaporate, so pool area is established by the heat transfer rate.
      The maximum extent of a burning pool is predicted to be significantly less than
      that of an unignited pool because the duration of the first regime is reduced by
      higher heat transfer rates. The maximum extent of an LNG pool is predicted to be
      larger upon accounting for blow down compared with using a constant average
      discharge rate. However, the maximum pool extent occurs only momentarily before
      retreating.

PMID- 17184913
TI  - Adsorption of Reactive Red 141 from wastewater onto modified chitin.
AB  - This research involved the adsorption of synthetic reactive dye wastewater (SRDW)
      by chitin modified by sodium hypochlorite and original chitin in batch
      experiments. The comparison of maximum adsorption capacity used the Langmuir
      model to describe SRDW adsorption onto chitin and modified chitin under a system
      pH of 11.0. Maximum dye adsorption by chitin increased from 133mgg(-1) to 167mgg(
      1) at temperatures of 30-60 degrees C, respectively. For modified chitin, the
      capacity decreased from 124mgg(-1) to 59mgg(-1) when the temperature increased
      from 30 degrees C to 60 degrees C, respectively. Both Na(2)SO(4) and Na(2)CO(3)
      increased in dye adsorption. The spectra of attenuated total reflectance Fourier
      transform infrared (ATR-FTIR) spectrometry confirmed the hydroxyl groups as
      functional groups of modified chitin, which affected the modification and the
      SRDW adsorption. The adsorbed dyes were eluted by distilled water and 1M NaOH to
      confirm the dye adsorption mechanism. Total elution of modified chitin and chitin
      were 92.76% and 55.29%, respectively. Although modified chitin had a maximum
      adsorption capacity less than chitin, elution of the dye from modified chitin was
      easier than chitin. Therefore, modified chitin could be suitable in a column
      system for dye pre-concentration as well as wastewater minimisation. In addition,
      the column study showed that modified chitin could be used for more than four
      cycles of adsorption and elution by distilled water.

PMID- 17184914
TI  - Adsorption of platinum (IV), palladium (II) and gold (III) from aqueous solutions
      onto L-lysine modified crosslinked chitosan resin.
AB  - Crosslinked chitosan resin chemically modified with L-lysine has been used to
      investigate the adsorption of Pt(IV), Pd(II) and Au(III) from aqueous solutions.
      Batch adsorption studies were carried out with various parameters, such as
      initial metal ion concentration, contact time, pH and temperature. The maximum
      adsorption capacity was found at pH 1.0 for Pt(IV), at pH 2.0 for Au(III) and
      Pd(II). Langmuir and Freundlich isotherm models were applied to analyze the
      experimental data. The best interpretation for the experimental data was given by
      the Langmuir isotherm and the maximum adsorption capacity was found to be 129.26
      mg/g for Pt(IV), 109.47 mg/g for Pd(II) and 70.34 mg/g for Au(III). The kinetic
      data was tested using pseudo-first-order and pseudo-second-order kinetic models.
      Kinetic data correlated well with the pseudo-second-order kinetic model,
      indicating that the chemical sorption was the rate-limiting step. Thermodynamic
      parameters like Gibbs free energy (DeltaG degrees), enthalpy (DeltaH degrees) and
      entropy (DeltaS degrees) were evaluated by applying the Van't Hoff equation. The
      thermodynamic study indicated that the adsorption process is spontaneous and
      exothermic in nature. The desorption studies were carried out using various
      reagents. The maximum percent desorption of precious metal ions were obtained
      when the reagent 0.7 M thiourea-2 M HCl was used.

PMID- 17184915
TI  - Chelating adsorption properties of PEI/SiO(2) for plumbum ion.
AB  - In this paper, a novel adsorption material PEI/SiO(2) with strong adsorption
      ability towards heavy-metal ions was prepared. In preparation of PEI/SiO(2),
      functional macromolecule polyethyleneimine (PEI) was grafted onto the surfaces of
      silica gel particles via the coupling effect of gamma-chloropropyl
      trimethoxysilane (CP). The adsorption properties of PEI/SiO(2) for Pb(2+) ion
      were studied by both static and dynamic methods. The experimental results show
      that PEI/SiO(2) possesses very strong adsorption ability for Pb(2+) ion, the
      saturated adsorption amount could reach to 17.5mgg(-1), and the empirical
      Langmuir isotherm was found to describe well the equilibrium adsorption data. The
      pH and grafting amount of PEI have great influence on the adsorption amount. The
      Pb(2+) ions adsorbed on PEI/SiO(2) are eluted easily by diluted hydrochloric acid
      solution.

PMID- 17184916
TI  - Analysis of the main factors affecting the evaluation of the radon dose in
      workplaces: the case of tourist caves.
AB  - High concentrations of radon exist in several workplaces like tourist caves
      mainly because of the low ventilation rates existing at these enclosures. In this
      sense, in its 1990 publication, the ICRP recommended that high exposures of radon
      in workplaces should be considered as occupational exposure. In developed caves
      in which guides provide tours for the general public great care is needed for
      taking remedial actions concerning radon, because in some circumstances forced
      ventilation may alter the humidity inside the cave affecting some of the
      formations or paintings that attract tourists. Tourist guides can work about 1900
      h per year, so the only option to protect them and other cave workers from radon
      exposure is to apply an appropriate system of radiation protection mainly based
      on limitation of exposure by restricting the amount of time spent in the cave.
      Because of the typical environmental conditions inside the caves, the application
      of these protecting actions requires to know some indoor air characteristics like
      particle concentration, as well as radon progeny behaviour in order to get more
      realistic effective dose values In this work the results of the first two set of
      radon measurements program carried out in 10 caves located in the region of
      Cantabria (Spain) are presented.

PMID- 17184917
TI  - Kv7.2-7.5 voltage-gated potassium channel (KCNQ2-5) opener, retigabine, reduces
      capsaicin-induced visceral pain in mice.
AB  - K(v)7.2-7.5 voltage-gated potassium channels (KCNQ2-5) are associated with M
      current and known to distribute in the nociceptive sensory pathway (e.g., dorsal
      root ganglia and spinal cord). Opening of these channels leads to cell membrane
      hyperpolarization that results in decreased neuronal action potentials. Since,
      KCNQ/M-current is located in the visceral sensory system, we examined the anti
      nociceptive effect of the KCNQ opener, retigabine, on visceral pain induced by an
      intracolonic injection of capsaicin in mice. Intraperitoneal administration of
      retigabine (1, 3 and 10 mg/kg) dose-dependently suppressed visceral pain behavior
      (i.e., the number of licking) induced by the capsaicin treatment and prolonged
      the latency to first licking. These data provide the first evidence that
      increased KCNQ channel conductance plays an inhibitory role in the visceral pain
      pathway.

PMID- 17184918
TI  - Lack of postmortem digestion of tapeworms in Golden hamsters experimentally
      infected with Taenia solium.
AB  - Taenia solium causes human neurocysticercosis, a public health problem in Mexico
      and other developing countries. Surprisingly, tapeworm carriers are very rarely
      found and in necropsy studies practically no tapeworms have been reported. In
      this paper we analyze the possibility that, after the death of the host,
      tapeworms could easily be destroyed in the intestine. Our experiments, performed
      in the hamster model, suggest that the absence of tapeworms in human intestine
      during necropsy is not due to postmortem digestion.

PMID- 17184919
TI  - Field evaluation of the efficacy and the safety of a combination of
      oxantel/pyrantel/praziquantel in the treatment of naturally acquired
      gastrointestinal nematode and/or cestode infestations in dogs in Europe.
AB  - In five multicentre field trials, the efficacy and safety of a combination of
      oxantel/pyrantel/praziquantel (Dolpac), Vetoquinol SA) in the treatment of
      naturally acquired gastrointestinal nematode and/or cestode infestation in dogs
      was evaluated in northern and southern Europe. Forty-eight investigators from
      France, Belgium, Germany, Italy and Spain enrolled 329 dogs to be treated with
      the tested combination; 235 of these dogs complied with the inclusion criteria of
      the protocol and had a tested helminth identified on Day 0. A pooled analysis was
      performed on each of the following helminth species: Toxocara canis, Ancylostoma
      caninum, Toxascaris leonina, Trichuris vulpis, Uncinaria stenocephala, Taenia
      spp. and Dipylidium caninum, which were isolated on Day 0. The main efficacy
      criterion was the egg per gram (epg) percent reduction of the nematodes and the
      absence of proglottids and or eggs for the cestodes. After treatment, dogs were
      examined on Day 7, Day 14 and Day 21. The efficacy of the combination against
      Toxocara canis was 99.1%, 98.8% and 98.9% on Day 7, Day 14 and Day 21,
      respectively. At the same occasions the efficacy was, respectively, 99.2%, 99.2%
      and 99.3% against Ancylostoma caninum, 97.3%, 97.2% and 98.4% against Trichuris
      vulpis, 98.4%, 98.8% and 98.8% against Uncinaria stenocephala, 98.9%, 99.5% and
      99.9% against Toxascaris leonina, 97.1%, 100% and 100% against Dipylidium caninum
      and 100% against Taenia spp.

PMID- 17184920
TI  - Structural characterization of a rhamnose-binding glycoprotein (lectin) from
      Spanish mackerel (Scomberomorous niphonius) eggs.
AB  - A rhamnose-binding glycoprotein (lectin), named SML, was isolated from the eggs
      of Spanish mackerel (Scomberomorous niphonius) by affinity and ion-exchange
      chromatographies. SML was composed of a non-covalently linked homodimer. The SML
      subunit was composed of 201 amino acid residues with two tandemly repeated
      domains, and contained 8 half-Cys residues in each domain, which is highly
      homologous to the N-terminal lectin domain of calcium-independent alpha
      latrotoxin receptor in mammalian brains. Each domain has the same disulfide
      bonding pattern; Cys10-Cys40, Cys20-Cys99, Cys54-Cys86 and Cys67-Cys73 were
      located in the N-terminal domain, and Cys108-Cys138, Cys117-Cys195, Cys152-Cys182
      and Cys163-Cys169 were in the C-terminal domain. SML was N-glycosylated at Asn168
      in the C-terminal domain. The structure of the sugar chain was determined to be
      NeuAc-Galbeta1-4GlcNAcbeta1-2Manalpha1-6-(NeuAc-Galbeta1-4GlcNAcbeta1-2Manalpha1
      3)Manbeta1-4GlcNAcbeta1-4GlcNAc-Asn.

PMID- 17184921
TI  - Antigen-mediated growth control of hybridoma cells via a human artificial
      chromosome.
AB  - Human artificial chromosome (HAC) vectors possess several characteristics
      sufficient for the requirements of gene therapy vectors, including stable
      episomal maintenance and mediation of long-term transgene expression. In this
      study, we adopted an antigen-mediated genetically modified cell amplification
      (AMEGA) system employing an antibody/cytokine receptor chimera that triggers a
      growth signal in response to a cognate non-toxic antigen, and applied it to
      growth control of HAC-transferred cells by adding an antigen that differed from
      cytokines that may manifest pleiotropic effects. We previously constructed a
      novel HAC vector, 21 Delta qHAC, derived from human chromosome 21, housed in CHO
      cells. Here, we constructed an HAC vector harboring an ScFv-gp130 chimera
      responsive to fluorescein-conjugated BSA (BSA-FL) as well as a model transgene,
      enhanced green fluorescent protein (EGFP), in CHO cells. The modified HAC was
      transferred into interleukin (IL)-6-dependent hybridoma 7TD1 cells by microcell
      mediated chromosome transfer, and the cells were subsequently found to show BSA
      FL-dependent cell growth and sustained expression of EGFP in the absence of IL-6.
      The AMEGA system in combination with HAC technology will be useful for increasing
      the efficacy of gene therapy by conferring a growth advantage on the genetically
      modified cells.

PMID- 17184922
TI  - Optical mapping of spatiotemporal emergence of functional synaptic connections in
      the embryonic chick olfactory pathway.
AB  - In order to understand the functional maturation of the CNS, it is essential to
      first describe the functional maturation of sensory processing. We have
      approached this topic by following the ontogenetic patterning of neural circuit
      formation related to cranial and spinal sensory input using voltage-sensitive dye
      imaging. In previous studies, we have described the functional maturation of
      synapses in brainstem/midbrain neural circuits. Here, we elucidate the functional
      maturation of forebrain circuits by investigating neural networks related to the
      olfactory nerve (N. I) of chicken embryo. In the isolated N. I-olfactory bulb
      forebrain preparation, application of electrical stimulation to N. I elicited
      excitatory postsynaptic potential (EPSP)-related slow optical signals in the
      olfactory bulb. The slow signal was mainly mediated by glutamate, and was easily
      fatigued with repetitive stimuli because of the immaturity of synapses in the
      embryonic CNS. Ontogenetically, the slow signal was detected from the 6-day
      embryonic stage, suggesting that functional synaptic connections between N. I and
      olfactory bulb emerge around this stage. In addition, from the 8-day embryonic
      stage, another response area was discriminated within the forebrain, which
      corresponded to the higher-ordered nucleus of the olfactory pathway. In
      comparison with our previous studies concerning the functional development of
      other cranial nerve-related sensory nuclei in the embryonic brainstem and
      midbrain, these results suggest that the olfactory pathway is functionally
      generated in the early stages of development when neural networks related to
      other visceral and somatic sensory inputs are also in the process of developing.

PMID- 17184923
TI  - Changes in Ca(2+)/calmodulin-dependent protein kinase II activity and its
      relation to performance in passive avoidance response and long-term potentiation
      formation in mice prenatally exposed to diethylstilbestrol.
AB  - We investigated the effects of prenatal exposure to diethylstilbestrol (DES), an
      endocrine disrupter on learning behavior and synaptic functions. Specifically, we
      determined the activity of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)
      and related kinases that play an essential role in long-term potentiation (LTP)
      in the hippocampus in mice that were prenatally exposed to DES. Treatment with
      DES resulted in increased CaMKII autophosphorylation and Ca(2+)-independent
      activity in the hippocampus and cortex of male mice. Impaired passive avoidance
      correlated with this increased CaMKII autophosphorylation, as did the enhanced
      early phase of LTP (E-LTP) in hippocampus. These data suggest that prenatal
      exposure to DES induces deficits in passive avoidance responses as a result of
      increased CaMKII activity and hippocampal LTP.

PMID- 17184924
TI  - Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium
      and valproate.
AB  - Mood stabilizing drugs lithium and valproate are the most commonly used
      treatments for bipolar disorder. Previous studies in our laboratory indicate that
      chronic treatment with lithium and valproate inhibits oxidative damage in primary
      cultured rat cerebral cortical cells. Glutathione, as the major antioxidant in
      the brain, plays a key role in defending against oxidative damage. The purpose of
      this study was to determine the role of glutathione in the neuroprotective
      effects of lithium and valproate against oxidative damage. We found that chronic
      treatment with lithium and valproate inhibited reactive oxygen metabolite
      H(2)O(2)-induced cell death in primary cultured rat cerebral cortical cells,
      while buthionine sulfoximine, an inhibitor of glutathione rate-limiting synthesis
      enzyme glutamate-cysteine ligase, reduced the neuroprotective effect of lithium
      and valproate against H(2)O(2)-induced cell death. Further, we found that chronic
      treatment with lithium and valproate increased glutathione levels in primary
      cultured rat cerebral cortical cells and that the effects of lithium and
      valproate on glutathione levels were dose-dependent in human neuroblastoma SH
      SY5Y cells. Chronic treatment with lithium and valproate also increased the
      expression of glutamate-cysteine ligase in both rat cerebral cortical cells and
      SH-SY5Y cells. In addition, chronic treatment with other mood stabilizing drugs
      lamotrigine and carbamazepine, but not antidepressants desipramine and
      fluoxetine, increased both glutathione levels and the expression of glutamate
      cysteine ligase in SH-SY5Y cells. These results suggest that glutathione plays an
      important role in the neuroprotective effects of lithium and valproate, and that
      glutathione may be a common target for mood stabilizing drugs.

PMID- 17184926
TI  - Roles of different subtypes of opioid receptors in mediating the ventrolateral
      orbital cortex opioid-induced inhibition of mirror-neuropathic pain in the rat.
AB  - Previous studies have demonstrated that opioid receptors in the prefrontal
      ventrolateral orbital cortex (VLO) are involved in anti-nociception. The aim of
      this current study was to examine whether opioid receptors in the VLO have
      effects on the hypersensitivity induced by contralateral L5 and L6 spinal nerve
      ligation (SNL), termed as mirror neuropathic pain (MNP) in the male rat. Morphine
      (1.0, 2.5, 5.0 microg) microinjected into the VLO contralateral to the SNL
      depressed the mechanical paw withdrawal assessed by von Frey filaments and the
      cold plate (4 degrees C)-induced paw lifting in a dose-dependent manner on the
      side without SNL. These effects were antagonized by microinjection of the non
      selective opioid receptor antagonist naloxone (1.0 mug) into the same VLO site.
      Microinjection of endomorphin-1 (5.0 microg), a highly selective mu-opioid
      receptor agonist, and [d-Ala(2), d-Leu(5)]-enkephalin (DADLE, 10 microg), a delta
      /mu-receptor agonist, also depressed the MNP. The effects of both drugs were
      blocked by selective mu-receptor antagonist beta-funaltrexamine (beta-FNA, 3.75
      microg), but the effect of the DADLE was not influenced by the selective delta
      receptor antagonist naltrindole (5.0 microg). Microinjection of the kappa-opioid
      receptor agonist spiradoline mesylate salt (U-62066) (100 microg) had no effect
      on the MNP. These results suggest that the VLO is involved in opioid-induced
      inhibition of the MNP and the effect is mediated by mu- (but not delta- and kappa
      ) opioid receptors.

PMID- 17184925
TI  - Role of acetylcholine transmission in nucleus accumbens and ventral tegmental
      area in heroin-seeking induced by conditioned cues.
AB  - The involvement of cholinergic transmission in heroin self-administration and the
      reinstatement of heroin-seeking was examined in rats trained to nose-poke for
      i.v. heroin. Systemic treatment with physostigmine, an inhibitor of
      acetylcholinesterase, modestly reduced the acquisition and rate of heroin self
      administration, and this suppression of heroin intake was reversed by
      pretreatment with scopolamine but not by mecamylamine. Following 10-14 days of
      self-administration, rats were left in the home environment for 14 days.
      Subsequently, rats were evaluated for extinction of nose-pokes during the first
      hour after being returned to the self-administration apparatus. One hour later a
      conditioned stimulus (house light, light in the nose-poke hole, sound of the
      infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine
      produced a dose-dependent inhibition of cue-induced reinstatement, but only the
      dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction
      test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance
      during acquisition of heroin self-administration. However, during a subsequent
      reinstatement test conducted in the absence of physostigmine pretreatment, heroin
      seeking was significantly below that of rats chronically pretreated with saline.
      To evaluate brain regions mediating the effects of systemic drug treatment on
      reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc)
      or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc
      prior to presenting conditioned cues inhibited the reinstatement of heroin
      seeking, without affecting extinction responding. In contrast, microinjection of
      physostigmine into the VTA augmented the reinstatement induced by conditioned
      cues and extinction responding. Inactivation of either NAc or VTA by
      microinjecting tetrodotoxin blocked both extinction responding and cue-induced
      reinstatement. These data demonstrate that cholinergic transmission influences
      heroin self-administration and reinstatement. Moreover, cue-induced reinstatement
      was inhibited by physostigmine in the NAc and potentiated by cholinergic
      stimulation in the VTA.

PMID- 17184927
TI  - Mecamylamine blocks nicotine-induced enhancement of the P20 auditory event
      related potential and evoked gamma.
AB  - Cigarette smoking is significantly more prevalent in individuals with
      schizophrenia than in non-affected populations. Certain neurocognitive deficits
      and disruptions common in schizophrenia may be altered by smoking, leading to the
      hypothesis that schizophrenics engage in smoking behavior to alleviate specific
      neurocognitive symptoms of the disorder. Additionally, research suggests that
      individuals with schizophrenia have altered auditory event-related potentials
      (ERPs) and abnormalities in evoked gamma oscillations which are both indices of
      sensory information processing. This study was conducted to examine the effect of
      acute administration of nicotine and the non-specific nicotinic antagonist
      mecamylamine on the P20 and N40 components of the ERP and evoked gamma
      oscillations in mice. Acute nicotine (1 mg/kg) significantly increased P20
      amplitude, an effect that was blocked by pretreatment with mecamylamine (2
      mg/kg). Additionally, acute nicotine increased the normal burst of evoked gamma
      following an auditory stimulus. The increase in evoked gamma was also blocked by
      mecamylamine pretreatment. Although acute nicotine decreased amplitude of the N40
      component, this decrease was not attenuated by mecamylamine. These results
      replicate findings that nicotine may enhance early sensory information processing
      through the nicotinic acetylcholinergic receptor system in an established model
      (ERPs) and extend these findings in an emerging, novel model (evoked gamma
      oscillations) of sensory information processing. The results also support the
      hypothesis that nicotine may be beneficial to individuals with deficits in
      neurocognitive functions, such as those suffering from schizophrenia.

PMID- 17184929
TI  - Astrocyte-derived estrogen enhances synapse formation and synaptic transmission
      between cultured neonatal rat cortical neurons.
AB  - Recent in vitro studies have found that astrocytes exert powerful control over
      the number of neuronal synapses, leading us to consider why glia can exert this
      control and what the underlying mechanism(s) may be. To understand the potential
      possibility, we studied the formation of synapses and synaptic function in
      primary rat cortical neurons. We found that primary cultured neonatal rat
      cortical astrocytes modulate synaptogenesis and synaptic function through
      producing and secreting estradiol into culture medium. The concentration of
      estradiol produced by pure cultured astrocytes increased in correspondence with
      the days of culture and the number of proliferating astrocytes, which peaked at
      266+/-22 ng/l around day 14 of culture. When astrocyte-conditioned medium (ACM)
      was added into pure cultured cortical neurons, the number of synapses formed
      between cortical neurons increased by nearly sixfold. The mean frequency and the
      amplitude of mini-postsynaptic currents (mPSCs) increased from 13+/-4 events/min
      and 20.5+/-2 pA to 73+/-16 events/min and 29.1+/-3 pA, respectively. In the
      meantime, the level of estrogen receptor-alpha (ER-alpha) expressed on neonatal
      rat cortical neurons was significantly up-regulated. Moreover, the effect of ACM
      on synaptic formation and transmission was blocked by tamoxifen (estrogen
      receptor antagonist) in culture. After the treatment of tamoxifen, the number of
      synapses on neurons decreased from 79+/-9 to 32+/-3. The mean amplitude and
      frequency of mPSCs were also dropped to 24.5+/-2 pA and 35+/-10/min,
      respectively. Unexpectedly, exogenic estradiol can mimic the effect of ACM on
      synaptic formation and transmission. Finally, to understand whether astrocyte
      derived estradiol regulates the synaptic transmission via presynapse, the release
      of presynaptic vesicle from neuron was monitored by FM 4-64 assay. The results
      showed that when ACM or exogenic estradiol was added into neurons, the kinetics
      of vesicle release speed are similar to that of neuronal cultured with
      astrocytes, which were faster than that of just pure neuronal cultures. These
      observations suggest that estrogen synthesized and secreted by astrocytes can
      regulate synapse formation and synaptic transmission.

PMID- 17184930
TI  - Relationship between cumulative effects of smoking and memory CD4+ T lymphocyte
      subpopulations.
AB  - Previous studies have found that smoking is a strong factor that increases
      peripheral blood CD4+ T lymphocytes. However, most studies did not assess the
      cumulative long-life exposure of smoking on differential lymphocyte populations.
      In this study, to clarify the association of smoking habits and circulating
      lymphocytes, we conducted a cross-sectional study of 60 male current smokers.
      Smoking status was estimated by number of cigarettes smoked per day, smoking
      years, and Brinkman Index (BI) as calculated by multiplying the number of
      cigarettes smoked per day by the smoking years. Counts of CD4+CD45RO+CD69+ T and
      CD4+CD45RO+ T lymphocytes were strongly and positively correlated with BI and
      remained highly significant after controlling for alcohol drinking, leisure-time
      physical activity, and caffeine intake (r(p)>.465, p<.001). These lymphocytes
      were also significantly correlated with the number of cigarettes smoked per day
      and smoking years, but the association was weaker than the BI. The findings
      suggest that the CD4+CD45RO+CD69+ T and CD4+CD45RO+ T lymphocytes are sensitive
      to cumulative effect of smoking, and may serve as a potential immuno-biomarker
      for active smoking.

PMID- 17184928
TI  - The case for 8,5'-cyclopurine-2'-deoxynucleosides as endogenous DNA lesions that
      cause neurodegeneration in xeroderma pigmentosum.
AB  - Patients with the genetic disease xeroderma pigmentosum (XP) lack the capacity to
      carry out a specific type of DNA repair process called nucleotide excision repair
      (NER). The NER pathway plays a critical role in the repair of DNA damage
      resulting from ultraviolet (UV) radiation. A subset of XP patients develops a
      profound neurodegenerative condition known as XP neurological disease. Robbins
      and colleagues [Andrews A, Barrett S, Robbins J (1978) Xeroderma pigmentosum
      neurological abnormalities correlate with the colony forming ability after
      ultraviolet irradiation. Proc Natl Acad Sci U S A 75:1984-1988] hypothesized that
      since UV light cannot reach into the human brain, XP neurological disease results
      from some form of endogenous DNA damage that is normally repaired by the NER
      pathway. In the absence of NER, the damage accumulates, causing neuronal death by
      blocking transcription. In this manuscript, I consider the evidence that a
      particular class of oxidative DNA lesions, the 8,5'-cyclopurine-2'
      deoxynucleosides, fulfills many of the criteria expected of neurodegenerative DNA
      lesions in XP. Specifically, these lesions are chemically stable, endogenous DNA
      lesions that are repaired by the NER pathway but not by any other known process,
      and strongly block transcription by RNA polymerase II in cells from XP patients.
      A similar set of criteria might be used to evaluate other candidate DNA lesions
      responsible for neurological diseases resulting from defects in other DNA repair
      mechanisms as well.

PMID- 17184931
TI  - Do tobacco countermarketing campaigns increase adolescent under-reporting of
      smoking?
AB  - This study assesses whether a national anti-tobacco campaign for youth could
      create a social context that would elevate social desirability response bias on
      surveys, as measured by an increase in under-reporting of smoking. This could
      give rise to data that falsely suggest a campaign-induced decline in youth
      smoking, or it could exaggerate campaign effects. Data were obtained from a
      national sample of 5511 students from 48 high schools that were matched to
      schools sampled for the 2002 National Youth Tobacco Survey (NYTS). Self-reported
      smoking was compared with biochemical indicators of smoking, measured using
      saliva cotinine. The rate of under-reporting detected was 1.3%. Level of truth
      exposure was not related to under-reporting. This study suggests that for high
      school students, anti-tobacco campaigns are not an important cause of social
      desirability responses on surveys, and that in general under-reporting smoking is
      not a major source of error in school-based surveys.

PMID- 17184932
TI  - The Nephrotic Syndrome is an immunoinflammatory disorder.
AB  - The Nephrotic Syndrome is still a therapeutic and physiopathological challenge.
      The clinical response to systemic immunosuppression shows that an
      immunoinflammatory disorder supports the nephrotic syndrome. Experimental (in
      vitro and in vivo) studies show that proteinuria may induce kidney secretion of
      proinflammatory and profibrotic cytokines and subsequent renal inflammation
      mediated by leukocyte recruitment. In turn,the infiltrating leukocytes contribute
      to renal damage by releasing proinflammatory and profibrotic cytokines (kidney
      acute remodelling). Chronic proteinuria maintains continuous local cytokine
      secretion and leukocyte influx into the glomerulus or the interstitial space
      (kidney chronic remodelling). In glomerular injury (podocyte injury), proteinuria
      itself, as well as glomerular secreted cyotokines, stimulates downstream tubular
      epithelial cells to secrete cytokines,as well. The mutual stimulation between
      proteinuria-cytokines-podocyte dysfunction-infiltrating leukocytes supports
      progressive tubular damage, renal fibrosis and glomerulosclerosis. Interfering
      with the cytokine network by inhibition/blockade of the cytokine receptor and its
      synthesis (via NFkB and the JAK/STAT intracellular signalling pathway) may
      represent a promising therapeutic option for systemic immunosuppression. Renal
      cytokine escape into systemic circulation may provide to hypercytokinemia stress
      syndrome,which could help to explain the increase in efferent renal sympathetic
      nerve activity (physiopathological sympathetic overactivity) observed during
      experimental nephrotic edema.

PMID- 17184933
TI  - Chemical components of Fraxinus species.
AB  - A wide range of chemical components including coumarins, secoiridoids,
      phenylethanoids, flavonoids, and lignans has been isolated from Fraxinus species.
      Extracts and metabolites have been found to possess antiinflammatory,
      immunomodulatory, antimicrobial, antioxidative, skin regenerating, photodynamic
      damage prevention, liverprotecting, diuretic and antiallergic activities. Some
      species find application in contemporary medicine. In the present review the
      literature data on the phytochemical and biological investigations on the genus
      Fraxinus are summarized up to the middle of 2004.

PMID- 17184934
TI  - Serological evidence of Mycoplasma cynos infection in canine infectious
      respiratory disease.
AB  - A high proportion of dogs suffer from respiratory disease when they are placed in
      kennels for vacation or re-homing. The role of Mycoplasma cynos as an initiating
      agent in canine infectious respiratory disease was investigated by examining the
      serological response of dogs to this organism at the time of entry into a large
      re-homing kennel. Forty-two paired serum samples from dogs (21-day interval) were
      examined for antibody to M. cynos using Western blotting. The development of
      antibody in the serum was related to clinical disease recorded over the same
      period. Sixty seven per cent of the dogs showed a two-fold or greater rise in
      antibody to M. cynos during the first 3 weeks in the kennel. Reactivity with a
      45kDa antigen was dominant. Of those showing a positive serological reaction, 80%
      had recorded clinical respiratory disease while 20% remained healthy. The
      findings of this study show that an antibody response to M. cynos is common in
      dogs entering the re-homing kennel and is positively related to the development
      of clinical respiratory disease.

PMID- 17184935
TI  - Identification of genotype 3 hepatitis E virus in fecal samples from a pig farm
      located in a Shanghai suburb.
AB  - Strains of hepatitis E virus (HEV) genotypes 1 and 4 have been detected on the
      Chinese mainland although there have been no previous reports of zoonotic
      genotype 3 HEV. In the present study, 65 swine fecal specimens were collected
      from five pig farms located in different Shanghai suburbs. RT-PCR and nested PCR
      were undertaken using partial nucleotide sequences of Open Reading Frame 2 (ORF2)
      of HEV to detect HEV RNA. Genetic analysis was based on alignments of an
      amplified 150-nt ORF2 sequence. RT-PCR revealed 15 HEV positive samples among 65
      pig fecal specimens examined. Phylogenetic analysis of the amplified sequences
      indicated seven HEV strains belonged to genotype 3 and eight strains to genotype
      4. This is the first time that genotype 3 hepatitis E virus has been identified
      on the Chinese mainland.

PMID- 17184936
TI  - Over-expression of neuropathy target esterase activity in bovine chromaffin cell
      cultures by adenovirus-mediated gene transfer.
AB  - Chromaffin cells in culture show high neuropathy target esterase (NTE) activity.
      It is well known that inhibition and specific modification of NTE by some
      organophosphorus (OPs) compounds induces a neurodegenerative neuropathy. It has
      been suggested that NTE is responsible for phosphatidylcholine homeostasis,
      although its role in neuropathy induction remains unclear. The cDNA of human NTE
      (4.4kbp) was inserted into an adenoviral vector. Bovine chromaffin cells cultured
      at 50,000 cells/well were incubated with the vector for 2h and after removing the
      volume of infection, cells were maintained in the incubator. After 24h, NTE
      activity was 6.8+/-0.5mU/10(6) cells in untreated cells and 14.8+/-1.5mU/10(6)
      cells, 19.3+/-2.9mU/10(6) cells, 24.8+/-0.9mU/10(6) cells and 30.9+/-1.0mU/10(6)
      cells in cells incubated with 2, 4, 8 and 16microl of vector, respectively. After
      60min of inhibition with mipafox increased concentrations, the calculated I(50)
      (60min) values were 5.5, 6.2 and 6.6microM for cells infected with 0, 2 and
      10microl of vector preparation. We confirm that the adenoviral vector containing
      the human NTE gene is active in bovine chromaffin cells in culture and that the
      NTE activity expressed by the vector shows the same inhibition pattern by the
      neuropathic OP mipafox as the NTE activity of bovine chromaffin cells and cells
      remained viable after the high NTE activity expression.

PMID- 17184937
TI  - Performance of different ovarian reserve markers for predicting the numbers of
      oocytes retrieved and mature oocytes.
AB  - OBJECTIVE: To assess the performance of different ovarian reserve tests for
      predicting the total numbers of oocytes retrieved and mature oocytes. METHODS: A
      retrospective study was performed on 71 women undergoing their first
      IVF/intracytoplasmic sperm injection treatment. Basal ovarian reserve screening
      was performed on days 2-3 of a spontaneous cycle. Patients were down-regulated
      with the GnRH agonist, whereas ovarian stimulation was carried out with
      recombinant FSH, starting from day 2 to 3 of the cycle. The main outcome measures
      were the numbers of oocytes retrieved and mature oocytes. RESULTS: The total
      number of oocytes was positively correlated with AFC (p<0.0001) and E(2) levels
      post-GnRH (p<0.004), whereas there was an inverse correlation with age
      (p<0.0001). The number of mature oocytes also correlated with AFC (p<0.008) and
      E(2) levels post-GnRH (p<0.009), and inversely with age (p<0.0004). Univariate
      linear regression of square root of number of oocytes (SQNO) shows that
      acceptable predictors of number oocytes, based on model significance and R(2) are
      AFC (R(2)=0.215), age (R(2)=0.24) and E(2) variation (R(2)=0.09). The following
      model is proposed to predict the number of mature oocytes: ln(MO)=ln(NO)
      2.09+0.028 AGE+0.03 BMI. CONCLUSION(S): The number of antral follicles and
      patient age appear to be good markers of ovarian response in IVF treatments.
      Additional information is provided by stimulated E(2) levels.

PMID- 17184938
TI  - Solid dispersions of itraconazole and enteric polymers made by ultra-rapid
      freezing.
AB  - The primary objective of the study is to investigate the influence of composition
      parameters including drug:polymer ratio and polymer type, and particle structure
      of enteric solid dispersions on the release of ITZ under sink and supersaturated
      dissolution conditions. Modulated differential scanning calorimetry (MDSC) was
      utilized to define the level of ITZ miscibility with each polymer. The
      compositions were completely miscible at 60% ITZ for both polymers and as high as
      70% in HP-55. High potency composition glass transition temperatures (T(g))
      correlated with predicted T(g)'s from the Gordon-Taylor equation, however,
      recrystallization exotherms revealed pure amorphous regions indicating that phase
      separation occurred during particle formation. Furthermore, in vitro studies
      including X-ray powder diffraction (XRD), scanning electron microscopy (SEM),
      surface area analysis (BET), and dissolution were performed to determine
      differences between low potency (completely miscible) and high potency (partially
      miscible) compositions. Dissolution studies on low potency ITZ compositions
      revealed that miscibility plays an active role in ITZ release under sink
      conditions, and square root diffusion through the enteric polymer is observed.
      Supersaturated dissolution profiles revealed high potency compositions had
      maximum saturation levels (C/Ceq(max)) between 10.6- and 8-times equilibrium
      solubility, but had higher cumulative extents of supersaturation, compared to low
      potency compositions which had C/Ceq(max) values of 15-19.6. However, these low
      potency compositions rapidly precipitated leading to significantly lower AUCs
      (p<0.05). The change in the miscibility of the solid dispersion had a pronounced
      effect of drug release (sink) while differences in potency influenced
      supersaturated dissolution profiles.

PMID- 17184939
TI  - Stabilization of phenylalanine ammonia lyase against organic solvent mediated
      deactivation.
AB  - A potential novel therapy for phenylketonuria involves oral administration of
      microencapsulated phenylalanine ammonia lyase (PAL), an enzyme that converts
      phenylalanine to transcinnamic acid. A drawback of this potential therapy is that
      encapsulated PAL retains only 23% of its activity. Microcapsules are prepared by
      emulsifying PAL in 10% hemoglobin solution with water-saturated ether (WSE) and
      subsequent addition of cellulose nitrate dissolved in ether:ethanol (E:E)
      mixture. The objective of this paper was to determine the contribution of
      emulsification to the overall loss in activity of encapsulated PAL, and to devise
      strategies to protect PAL against such loss in activity. Emulsification was
      simulated by stirring the aqueous phase containing PAL with the organic phase.
      The mixture was then centrifuged, and the protein content and catalytic activity
      of PAL in the aqueous phase was measured. Emulsification of PAL solution with WSE
      caused no loss in activity but resulted in a loss in protein content of aqueous
      phase. Size exclusion chromatography and gel electrophoresis studies showed that
      the loss was primarily due to the specific loss of impurities in the PAL sample.
      Emulsification of PAL solution with E:E resulted in a 50% decrease in its
      activity. Among the additives, hydroxypropyl-gamma-cyclodextrin and hydroxy
      propyl-beta-cyclodextrin protected PAL against emulsion mediated loss in
      activity.

PMID- 17184940
TI  - Crystallization rate of amorphous nifedipine analogues unrelated to the glass
      transition temperature.
AB  - To examine the relative contributions of molecular mobility and thermodynamic
      factor, the relationship between glass transition temperature (T(g)) and the
      crystallization rate was examined using amorphous dihydropyridines (nifedipine
      (NFD), m-nifedipine (m-NFD), nitrendipine (NTR) and nilvadipine (NLV)) with
      differing T(g) values. The time required for 10% crystallization, t(90), was
      calculated from the time course of decreases in the heat capacity change at T(g).
      The t(90) of NLV and NTR decreased with decreases in T(g) associated with water
      sorption. The t(90) versus T(g)/T plots almost overlapped for samples of
      differing water contents, indicating that the crystallization rate is determined
      by molecular mobility as indicated by T(g). In contrast, differences in the
      crystallization rate between these four drugs cannot be explained only by
      molecular mobility, since the t(90) values at a given T(g)/T were in the order:
      NLV>NTR>NFD approximately m-NFD. A lower rate was obtained for amorphous drugs
      with lower structural symmetry and more bulky functional groups, suggesting that
      these factors are also important. Furthermore, the crystallization rate of NTR in
      solid dispersions with poly(vinylpyrrolidone) (PVP) and hydroxypropyl
      methylcellulose (HPMC) decreased to a greater extent than expected from the
      increased T(g). This also suggests that factors other than molecular mobility
      affect the crystallization rate.

PMID- 17184941
TI  - Molecular mechanism involved in the transport of a prodrug dopamine glycosyl
      conjugate.
AB  - We have previously demonstrated that dopamine conjugation to glucose allows it to
      induce therapeutic effects against Parkinson's disease after intravenous
      administration. In this paper we demonstrate that, unlike dopamine, the prodrug
      glu-dopamine is a transportable substrate of glucose transporters. Towards this,
      the effect of glucose-conjugation on the affinity and uptake of dopamine have
      been assessed in vitro, using human retinal pigment epithelium (HRPE) cells.
      Glucose transporter-mediated uptake was measured using [(3)H]3-O-methylglucose
      ([(3)H]3-O-MG) as the tracer. The uptake was found to be rapid and hyperbolically
      related to its concentrations (K(t)=7.8+/-1.2mM and V(max)=54+/-2 nmol/min mg
      protein). Inhibition experiments showed that dopamine was able to interact with
      glucose carriers only when conjugated to glucose (IC(50)=2.6+/-0.6mM). HPLC
      analysis of HRPE cell extracts showed that both dopamine and the prodrug permeate
      the cell, but only the uptake of the prodrug is inhibitable by glucose. This
      confirms that glucose transporters mediate the transport of the prodrug glu
      dopamine, but not of dopamine. HRPE cells is therefore proposed as a promising
      model for in vitro studies involving the glucose transporter-mediated transport
      of drugs and their conjugates.

PMID- 17184942
TI  - Expression of adhesion molecular proteins in the cochlear lateral wall of normal
      and PARP-1 mutant mice.
AB  - Sound can damage peripheral cochlear function through a number of mechanisms, and
      emerging evidence suggests that inflammation may be one of them. Using
      immunohistochemistry and poly (ADP-ribose) polymerase-1 (PARP-1) mutant mice, we
      tested whether PARP-1 contributes to loud-sound induced cochlear lateral wall
      damage by triggering inflammatory effects, including upregulating intercellular
      adhesion molecule-1 (ICAM-1), P-selectin and platelet-endothelial cell-adhesion
      molecule-1 (PECAM-1). In control conditions, we found that there was no
      detectable poly-ADP-ribose (PAR) in the marginal cells and microvessels. ICAM-1
      was expressed only at low levels in the vessels of the stria vascularis and the
      spiral ligament. P-selectin and PECAM-1 were barely detected and only in the
      vessels of the spiral ligament. Following loud-sound exposure, PAR was detected
      in numbers of marginal cells and some vessels of the spiral ligament. Also, an
      elevated expression of ICAM-1 was demonstrated in some vessels of the stria
      vascularis and spiral ligament. Increased expression of P-selectin and PECAM-1
      were mainly located in the vessels of the spiral ligament, while increased
      populations of non-migrated and migrated leukocytes were observed in the area of
      the spiral ligament. However, neither increased expression of adhesion proteins
      nor increased population of leukocytes, were observed in the PARP-1 knockout
      mouse. We thus conclude that loud-sound stress activates the expression of
      adhesion molecular proteins in the lateral wall and that PARP-1 modulates
      inflammation-linked protein expression and leukocyte migration.

PMID- 17184943
TI  - NAC for noise: from the bench top to the clinic.
AB  - Noise-induced hearing loss (NIHL) is an important etiology of deafness worldwide.
      Hearing conservation programs are in place and have reduced the prevalence of
      NIHL, but this disorder is still far too common. Occupational and recreational
      pursuits expose people to loud noise and ten million persons in the US have some
      degree of noise-induced hearing impairment. It is estimated that 50 million in
      the US and 600 million people worldwide are exposed to noise hazards
      occupationally. Noise deafness is still an important and frequent cause of
      battlefield injury in the US military. A mainstay of hearing conservation
      programs is personal mechanical hearing protection devices which are helpful but
      have inherent limitations. Research has shown that oxidative stress plays an
      important role in noise-induced cochlear injury resulting in the discovery that a
      number of antioxidant and cell death inhibiting compounds can ameliorate deafness
      associated with acoustic trauma. This article reviews one such compound, N
      acetylcysteine (NAC), in terms of its efficacy in reducing hearing loss in a
      variety of animal models of acute acoustic trauma and hypothesizes what its
      therapeutic mechanisms of action might be based on the known actions of NAC.
      Early clinical trials with NAC are mentioned.

PMID- 17184944
TI  - A phytotherapeutic extract of Equisetum myriochaetum is not genotoxic either in
      the in vivo wing somatic test of Drosophila or in the in vitro human micronucleus
      test.
AB  - Equisetum myriochaetum is a Mexican plant used in folk medicine to treat kidney
      diseases and type 2 diabetes mellitus. The main constituents of the phytoextract
      are flavonol glycosides (kaempferol), phytoesterols and carbohydrates. In this
      study, phytotherapeutic extracts from Equisetum myriochaetum were investigated
      for genotoxicity in the in vivo wing spot test in Drosophila melanogaster and in
      the in vitro human micronucleus test. No acute toxicity of the phytoextract could
      be determined in Drosophila or in human lymphocytes in culture, ranging from 0.78
      microg/ml to 3700 microg/ml for the wing assay and between 12.5 microg/ml and 500
      microg/ml for the micronucleus test. The Drosophila wing somatic mutation and
      recombination test (SMART) was applied in the standard version with basal
      biotransformation activity as well as in a variant version with increased
      cytochrome P450-dependent bioactivation capacity. The ranges of exposure
      concentrations for these genotoxicity experiments were between 0.78 microg/ml and
      500 microg/ml. The human micronucleus test in vitro was performed with cultured
      lymphocytes obtained from four healthy donors. The concentrations assayed for
      these experiments ranged from 12.5 microg/ml to 500 microg/ml. No statistically
      significant increase was observed between treated series when compared with a
      concurrent negative (water solvent) control series in either assay. The results
      demonstrate clearly that the phytotherapeutic extract from Equisetum
      myriochaetum, under the experimental conditions tested, is not genotoxic in the
      in vivo experiments or in the in vitro studies.

PMID- 17184945
TI  - Markers of chronic alcohol use in hair: comparison of ethyl glucuronide and
      cocaethylene in cocaine users.
AB  - Two direct ethanol metabolites, namely ethyl glucuronide (EtG) and cocaethylene
      (CE), in the hair of cocaine (COC) users were compared in this study. Hair
      samples (n=68) were submitted to the determination of EtG (by liquid
      chromatography-electrospray-tandem mass spectrometry) and of COC and metabolites,
      including CE (by gas chromatography-mass spectrometry). Quantitative and
      qualitative results were compared. No quantitative correlation was found between
      EtG and CE, as well as between EtG and the cocaethylene concentration divided by
      the concentration of COC and its metabolites (benzoylecgonine and ecgonine
      methylester, as COC equivalents). Nevertheless, many factors are supposed to
      affect the amount of the two substances incorporated in the hair matrix, such as
      the subject's habits in ethanol and COC use, genetic variability in the
      metabolism of both substances, and the different chemical and physical properties
      of EtG and CE. When establishing a cut-off of 4 pg/mg for EtG and of 200 pg/mg
      for CE, 47 samples tested positive for EtG and 41 samples tested positive for CE;
      12 samples out of the 47 EtG-positives tested negative for CE (25%), whereas 6
      samples out of the 41 CE-positives tested negative for EtG (15%). According to
      these data, EtG appears to be a more sensitive and specific marker of non
      moderate alcohol users than CE.

PMID- 17184946
TI  - Benign vascular lesions involving the external ear canal.
AB  - Benign vascular lesions include various forms whose classification has created
      some controversies in the literature. The observation of two rare cases of
      vascular bulge of the external ear canal prompted us to analyze the essential
      features of these lesions. One case was observed during an episode of otitis
      media, the other one was an incidental finding, and both are still on follow-up
      without treatment. The lesions are unmodified after 4 and 10 years, respectively.
      Vascular malformations can be differentiated from vascular tumors since they are
      present at birth, are generally stable, and do not involute. An attending
      strategy is justified unless symptoms occur.

PMID- 17184947
TI  - Beneficial effects of sub-chronic activation of glucagon-like peptide-1 (GLP-1)
      receptors on deterioration of glucose homeostasis and insulin secretion in aging
      mice.
AB  - Aging is associated with an increased incidence of glucose intolerance and type 2
      diabetes. Glucagon-like peptide-1 (GLP-1) is an important insulinotropic peptide
      secreted from the gastrointestinal tract in response to nutrient absorption. The
      present study was designed to assess the sub-chronic glucose regulatory effects
      of the potent long-acting GLP-1 receptor agonist, (Val(8))GLP-1, in aging 45-49
      week old mice. Daily injection of (Val(8))GLP-1 (25 n mol/kg body weight) for 12
      days had no significant effect on food intake, body weight, non-fasting plasma
      glucose and insulin concentrations. However, after 12 days, the glycaemic
      response to intraperitoneal glucose was improved (P<0.05) in (Val(8))GLP-1
      treated mice. In keeping with this, glucose-mediated insulin secretion was
      enhanced (P<0.05) and insulin sensitivity improved (P<0.05) compared to controls.
      These data indicate that sub-chronic activation of the GLP-1 receptor by daily
      treatment with (Val(8))GLP-1 counters aspects of the age-related impairment of
      pancreatic beta-cell function and insulin sensitivity.

PMID- 17184949
TI  - Assessment of risk in radiology using malpractice RVU.
AB  - INTRODUCTION: Analysis on the causes and remedies needed to reduce the incidence
      of malpractice has been under continual studies, although limited data is
      available regarding quantitative evaluation of the risk. OBJECTIVES: To determine
      radiological risk in a preventive and quantitative manner and verify if the
      malpractice relative value units (MP-RVU) are a good indicator of associated risk
      factors. MATERIALS AND METHODS: Radiological examinations executed by our
      Radiology Department in 2000-2004 have been codified according to nomenclature
      HCPCS (Healthcare Common Procedure Coding System) used by United States of
      America Centers for Medicare and Medicaid Services (CMS). For every examination
      was calculated the annual weight of malpractice. The data has been groupped in
      macroaggregates by methodology. The ratio MP-RVU/no. examinations has been
      considered as an index of insurance risk (MP index) RESULTS: A total of 133,005
      examinations were performed, which produced 25,252 MP-RVU points, the total mp
      index was 0.193. Traditional radiology represents 38% of the examinations,
      accounting for 8% of MP-RVU with a MP index=0.039. Ultrasound represents 35% of
      the examinations, accounting for 23% of MP-RVU with a MP index=0.125. CT
      represents 13% of the examinations, accounting for 28% of MP-RVU with a MP
      index=0.434. MR represents 11% of the examinations, accounting for 39% of MP-RVU
      with a MP index=0.667. CONCLUSIONS: Malpractice relative value units (MP-RVU) are
      indicative of the risk considered globally and when subgrouped. MP index
      correlates this risk with number of exams carried out divided by methodology.
      This model providing quantitative data for projects concerning risk management
      and in allowing the correlation between data obtained in different departments.

PMID- 17184948
TI  - Aging, B lymphopoiesis, and patterns of leukemogenesis.
AB  - The production of B lymphocytes begins to decline steadily early in adult life
      and is severely compromised in the elderly. This occurrence has been attributed
      to intrinsic defects in early hematopoietic progenitors and B cell precursors as
      well as to microenvironmental changes in aged bone marrow. The aim of this review
      is to present an overview of B lymphocyte senescence and its underlying causes
      and to discuss its impact on immune function and leukemogenesis in aged
      individuals.

PMID- 17184950
TI  - Breast imaging reporting and data system (BI-RADS) or French "classification ACR"
      What tool for what use? A point of view.
AB  - The American College of Radiology Task Force on Breast Cancer published in 2003
      the fourth edition of BI-RADS for Mammography. It is a lexicon of mammography
      terms including illustrations of each feature described, followed by a reporting
      format with assessment categories according to the degree of concern. The aim is
      to reduce inconsistencies in mammography reports and recommendations for
      assessment, to facilitate outcome monitoring and to allow each radiologist to
      audit his own mammography practice. In France, the Societe Francaise de
      Radiologie acquired the rights to translate BI-RADS, word for word and without
      adaptation or influence. The last edition was published in 2004. Simultaneously,
      French Haute Autorite de Sante and National Committee for Breast Cancer Screening
      proposed to all community practice mammography facilities a classification of
      detected abnormalities stating more clearly than BI-RADS do which feature has to
      be included in such and such assessment category and how to manage it. This
      "classification ACR" is adapted from BI-RADS but strongly influenced by the
      context of the French nationwide screening programme, and by European
      recommendations to limitate undesirable risks of screening such as false positive
      and overdiagnosis. The differences between the two systems are discussed.

PMID- 17184951
TI  - Development and validation of a sensitive liquid chromatographic method for the
      analysis of a novel radioprotectant: ON 01210.Na.
AB  - ON 01210.Na is a chlorobenzylsulfone derivative with potential property to
      mitigate the effects of accidental or intentional exposure to life threatening
      levels of radiation. A simple and sensitive HPLC method was developed and
      validated for the assay of ON 01210.Na. The isocratic system used a mobile phase
      consisting of acetonitrile:0.1% trifluroacetic acid in water (60:40, v/v) at a
      flow rate of 1 ml/min. The method used a C-18 Gemini column (250 mm x 4.6 mm)
      with column effluents monitored at 254 nm. Forced degradation of the drug was
      achieved by autoclaving ON 01210.Na with 0.05 N HCl, 0.05 N NaOH or 1.5% (v/v)
      hydrogen peroxide. The assay validation parameters evaluated include specificity,
      linearity, precision, accuracy and sensitivity. The retention time of the drug
      and the other effluents were well within 7 min. Standard curves were linear over
      the concentration range of 10-500 microg/ml. The R.S.D. values for the within-day
      and day-to-day precision ranged from 0.4 to 2.5 and 2.2 to 4.4%, respectively.
      The R.S.D. for accuracy measurement ranged from 0.85 to 1.7%. The critical level,
      the detection level and the determination level for this assay were 2.86+/-0.67,
      5.69+/-0.67 and 15.6+/-1.8 microg/ml, respectively. A simple, sensitive and
      stability indicating HPLC assay was developed and validated for the analysis of a
      novel radioprotectant. This method was used to evaluate the aqueous as well as
      solid-state stability of this drug during autoclaving.

PMID- 17184952
TI  - Determination of bismuth in pharmaceutical products using
      methyltriphenylphosphonium bromide as a molecular probe by resonance light
      scattering technique.
AB  - A method for the determination of bismuth in pharmaceutical products using
      methyltriphenylphosphonium bromide as a molecular probe based on the resonance
      light scattering (RLS) technique was developed. In the presence of Tween-20,
      bismuth reacts with a large excess of I(-) to form [BiI(4)](-), which further
      reacts with methyltriphenylphosphonium bromide (MTPB) to form an ion-association
      compound. This resulted in a significant enhancement of RLS intensity and the
      appearance of the corresponding RLS spectral characteristics. The enhanced RLS
      intensity was directly proportional to the concentration of Bi(III) in the range
      of 0.001-1.50 microg/ml for the system. The detection limit was 0.98 ng/ml. The
      characteristics of RLS spectra of the complex, the optimum conditions and the
      influencing factors were investigated. The method has high selectivity and was
      applied to the determination of Bi(III) in pharmaceutical products with
      satisfactory results, which were in agreement with those of the official method
      and atomic absorbance spectrometry (AAS).

PMID- 17184953
TI  - Therapeutic drug monitoring of tacrolimus with the dried blood spot method.
AB  - In a preliminary investigation an assay for tacrolimus based on fingerprick
      sampling and consecutive application as a blood spot on sampling paper has been
      developed. The dried blood spot was analysed by HPLC-tandem mass spectrometry.
      The validated range was 1-30 microg/l. Intra- and inter-assay variability for
      precision and accuracy was <7.5% and 15%, respectively. Tacrolimus concentrations
      of 24 stable out patients were compared after both blood spot sampling and
      conventional venous sampling. Method agreement was investigated with the methods
      of Passing and Bablok and Bland Altman and proved suitable for clinical use. The
      dried blood spot method for tacrolimus seems promising for patient monitoring.

PMID- 17184954
TI  - Extraction spectrophotometric determination of aluminum in dialysis concentrates
      with 3,5-ditertbutylsalicylfluorone and ionic liquid 1-butyl-3
      trimethylsilylimidazolium hexafluorophosphate.
AB  - The paper describes a highly sensitive and selective extraction
      spectrophotometric method for determination of aluminum in dialysis concentrates
      with new reagent 3,5-ditertbutylsalicylfluorone abbreviated as DTBSF, in which
      the ionic liquid 1-butyl-3-trimethylsilylimidazolium hexafluorophosphate
      abbreviated as [C4tmsim][PF6] was used as novel medium for liquid/liquid
      extraction of aluminum(III). Under optimal condition, DTBSF reacted with
      aluminum(III) to form a neutral Al-DTBSF complex rapidly, the complex was then
      extracted into the [C4tmsim][PF6] phase, the absorbance of the complex in ionic
      liquid at 542 nm was recorded and used to determine aluminum(III). The apparent
      molar absorptivity of the complex and detection limit were found to be 3.52x10(6)
      l mol(-1) cm(-1) and 0.06 microg/l, respectively. The absorbance of the complex
      at 542 nm increases linearly with the concentration of aluminum(III) up to 3
      microg of aluminum(III) in 250 ml of aqueous solution. The interference study
      show the determination of aluminum is free from interferences of almost all
      positive and negative ions found in dialysis concentrate samples. The
      determination of aluminum in dialysis concentrates were carried out by the
      present method and electrothermal atomic absorption spectrometry (GTAAS). The
      results were satisfactorily comparable so that the applicability of the proposed
      method with the ionic liquid system was also investigated. Moreover, the
      synthesis of and conditions for the formation and extraction of Al-DTBSF complex
      were investigated as well.

PMID- 17184955
TI  - Recent developments and future prospects of Vitreoscilla hemoglobin application
      in metabolic engineering.
AB  - In hypoxic conditions, bacteria express a kind of hemoglobin, which is proposed
      to enhance respiration and energy metabolism by promoting oxygen delivery.
      Bacteria hemoglobin from Vitreoscilla stercoraria - Vitreoscilla hemoglobin
      (VHb), when expressed in various hosts in oxygen-limited conditions, has been
      shown to improve growth, protein secretion, metabolite productivity and stress
      resistance of hosts, thus rendering the protein promising in metabolic
      engineering, especially in plant metabolism optimization. In this review, many
      well-studies areas are presented to illustrate the potential of VHb application
      in biotechnology industry, to discuss the cellular mechanisms of VHb function and
      to show the wide variety of approaches taken within the field.

PMID- 17184956
TI  - Induction of tyrosine hydroxylase expression by the transcription factor Pitx3.
AB  - Transcription factors are fate determining regulatory factors in dopaminergic
      neuronal development and differentiation. Among them, Nurr1 is the most
      extensively studied, but the importance of Pitx3 has recently been appreciated.
      Over-expression of both factors has been utilized to enhance the dopaminergic
      differentiation of stem cells for transplantation into models of Parkinson's
      disease. Previous studies however have seen conflicting results regarding the
      induction of tyrosine hydroxylase expression and dopaminergic differentiation
      induced by over-expression of Pitx3. Here we show that over-expression of Pitx3
      and Nurr1 induced endogenous tyrosine hydroxylase expression as well as a
      tyrosine hydroxylase promoter-reporter construct in a human non-neuronal and
      mouse embryonic stem cell lines. Combined simultaneous expression of Nurr1 and
      Pitx3 however did not lead to enhancement of tyrosine hydroxylase expression over
      that of either factor alone in either of the cell lines or with either method.
      These results suggest that other regulatory elements may also be involved in
      regulation of tyrosine hydroxylase expression. There was also a lack of a
      correlation between the expression levels of tyrosine hydroxylase with that of
      the transcription factor constructs. To yield a robust dopaminergic
      differentiation a combinatorial or successive treatment with different
      transcription factors may be more effective.

PMID- 17184957
TI  - The acceptability of physical activity programming within a smoking cessation
      service for individuals with severe mental illness.
AB  - OBJECTIVE: There is a high prevalence of smoking and physical inactivity among
      individuals with severe mental illness (SMI). The current study assessed the
      acceptability of introducing physical activity, including perceived advantages
      and disadvantages, as an adjunct to a smoking cessation service within this
      population. METHODS: 109 participants with SMI who were receiving smoking
      cessation treatment completed a survey assessing perceived interest in physical
      activity and a 24-item decisional balance questionnaire reflecting potential
      advantages and disadvantages of becoming more physically active. RESULTS: The
      majority of the participants reported being interested in assistance in becoming
      more active [63% (69/109)]. The highest rated advantages reported were 'It would
      improve my health or reduce my risk of disease' and 'It would improve how I feel
      about myself'. Cost, and being active by oneself were the most frequently
      reported barriers. CONCLUSION: This study suggests that many individuals with SMI
      seeking treatment for smoking cessation may also be receptive to assistance in
      becoming more physically active. Such individuals endorse both advantages and
      disadvantages more frequently than those not interested. PRACTICE IMPLICATIONS:
      This study provides preliminary support for the acceptability of adding physical
      activity as a smoking cessation strategy with SMI individuals. Addressing salient
      barriers will be critical to integrating physical activity within this smoking
      cessation service.

PMID- 17184959
TI  - A national surveillance system for tracking tobacco news stories.
AB  - BACKGROUND: Two of the major goals of tobacco prevention and control activities
      are to change social norms and influence policy. The news media can play an
      important role for achieving both goals. METHODS: The Centers for Disease Control
      and Prevention's Office on Smoking and Health created a surveillance system to
      track tobacco stories in the news media beginning in 2004. The system was
      developed based on reviewing lessons from previous news media tracking efforts,
      including defining the purpose of the system, using a parsimonious approach to
      sample media outlets, and attending to data-quality issues. Tobacco news stories
      were systematically identified and coded from ten newspapers, four news wire
      services, and seven national television networks. RESULTS: Findings indicated
      that from January 2004 through June 2005, tobacco-related stories were in
      selected major newspapers virtually every day. More than 70% of all newspaper
      stories contained one of only three main story themes: policy or regulation
      (31.0%), legal issues (23.8%), or health effects or statistics (18.1%).
      Television news stories on tobacco were much less common, but increased
      substantially during the first 6 months of 2005 compared to 2004. Health
      effects/statistics (50.5%) were the dominant theme for television, with
      policy/regulation a distant second (19.5%). CONCLUSIONS: Tobacco-related media
      coverage can be systematically tracked and characterized. These findings may have
      value to public health researchers and policymakers who wish to evaluate efforts
      to curb tobacco-related disease.

PMID- 17184958
TI  - Organization, financing, promotion, and cost of U.S. quitlines, 2004.
AB  - BACKGROUND: Quitlines have been established as an effective, evidence-based,
      population-wide strategy to deliver smoking-cessation treatment, and are now
      available in most states across America. However, little is known about the
      organization, financing, promotion, and cost of state quitlines. METHODS: In
      2004, the North American Quitline Consortium surveyed the 50 states and
      Washington DC to obtain information about state quitlines. Data were analyzed in
      fall 2005 through spring 2006. Analyses of these data are reported in this paper.
      RESULTS: Analyses were limited to the 38 states that reported having a quitline
      in 2004. State governments funded most (89.5%) quitlines. Median state quitline
      operating budgets in 2004 were 500,000 dollars; this translates into a modest
      annual median operating cost of 0.14 dollar per capita or 0.85 dollar per adult
      smoker. A lesser amount was spent for quitline promotion. Quitline services
      varied, with 97.4% of respondents providing mailed self-help resources, 89.5%
      providing proactive telephone counseling, and 89.2% providing referrals to other
      services. Many quitlines provide services in languages other than English. Only
      21.1% of quitlines reported providing cessation medication at no cost.
      Promotional strategies varied widely. CONCLUSION: A large majority of U.S.
      smokers live in states with tobacco quitlines, which provide cessation treatment
      at a remarkably modest per capita cost. There is a great deal of congruence in
      services and promotional strategies among states. Further research is required to
      determine how external factors such as the federal National Network of Tobacco
      Cessation Quitlines funding for state quitlines and the availability of a
      national portal number (1-800-QUITNOW), both implemented in 2004, affect state
      quitlines. Additional research to evaluate the cost effectiveness of quitline
      services is also warranted.

PMID- 17184960
TI  - HIV incidence and CDC's HIV prevention budget: an exploratory correlational
      analysis.
AB  - BACKGROUND: The central evaluative question about a national HIV prevention
      program is whether that program affects HIV incidence. Numerous factors may
      influence incidence, including public investment in HIV prevention. Few studies,
      however, have examined the relationship between public investment and the HIV
      epidemic in the United States. METHODS: This 2006 exploratory analysis examined
      the period from 1978 through 2006 using a quantitative, lagged, correlational
      analysis to capture the relationship between national HIV incidence and Centers
      for Disease Control and Prevention's HIV prevention budget in the United States
      over time. RESULTS: The analyses suggest that early HIV incidence rose in advance
      of the nation's HIV prevention investment until the mid-1980s (1-year lag
      correlation, r=0.972, df=2, p <0.05). From that point on, it appears that the
      nation's investment in HIV prevention became a strong correlate of HIV incidence
      (1-year lag correlation, r=-0.905, df=18, p <0.05). CONCLUSIONS: This exploratory
      study provides correlational evidence of a relationship between U.S. HIV
      incidence and the federal HIV prevention budget over time, and calls for further
      analysis of the role of funding and other factors that may influence the
      direction of a nation's HIV epidemic.

PMID- 17184961
TI  - Utilitarian bicycling: a multilevel analysis of climate and personal influences.
AB  - BACKGROUND: Increasing utilitarian bicycling in urban areas is a means to reduce
      air and noise pollution, increase physical activity, and reduce the risk of
      chronic diseases. We investigated the impact of individual- and city-level
      characteristics on bicycling in Canadian cities to inform transportation and
      public health policies. METHODS: The study population included 59,899 respondents
      to the 2003 Canadian Community Health Survey (CCHS) living in cities with
      populations greater than 50,000. In 2005, data on individual characteristics were
      drawn from the CCHS, and city-level climate data from Environment Canada records.
      Separate multilevel logistic regression models were developed for the general
      (nonstudent) and student populations. RESULTS: The proportion of the urban
      population reporting bicycling in a typical week was 7.9%, with students cycling
      more than nonstudents (17.2% vs 6.0%). In the general population, older age,
      female gender, lower education, and higher income were associated with lower
      likelihood of cycling. More days of precipitation per year and more days of
      freezing temperatures per year were both associated with lower levels of
      utilitarian cycling (odds ratios [ORs] for every 30-day increase in
      precipitation=0.84, 95% confidence interval [CI]=0.74-0.94, and for every 30-day
      increase in freezing temperatures OR=0.91, 95% CI=0.86-0.97). There was less
      variation in the proportion of students who cycled by age and income, and only
      the number of days with freezing temperatures influenced bicycling. CONCLUSIONS:
      Bicycling patterns are associated with individual demographic characteristics and
      the climate where one lives. This evidence might be useful to guide policy
      initiatives for targeted health promotion and transportation infrastructure.

PMID- 17184962
TI  - Colonoscopy demand and capacity in New Hampshire.
AB  - BACKGROUND: Screening for colorectal cancer has been clearly shown to decrease
      the incidence and mortality from this disease. Accurate information about the
      demand and capacity for screening, particularly with colonoscopy, is critical in
      planning screening strategies. National assessments have recently begun;
      estimates of smaller geographic regions should improve the accuracy of national
      estimates, as well as inform strategies for individual states. This study
      evaluates the demand and capacity for colonoscopy in the state of New Hampshire.
      METHODS: All endoscopy sites in the state of New Hampshire were contacted to
      determine their number of endoscopists, monthly colonoscopies, and estimates of
      the percentage of colonoscopy done for screening. Barriers to increasing current
      capacity were also assessed. The capacity estimates were compared to demand
      estimates based on population census figures. Data were collected in 2003 to 2004
      and analyzed in 2005 to 2006. RESULTS: One hundred fourteen endoscopists at 36
      centers performed 49,352 colonoscopies in 2002, an average of 39 to 43 total
      monthly colonoscopies per endoscopist. Approximately 60% were estimated to have
      been done for screening. Estimated demand was approximately twice the available
      capacity for screening and surveillance. The impact of factors such as
      compliance, percent screening, and population growth were assessed to inform
      future screening strategies. CONCLUSIONS: In 2002, demand for screening
      colonoscopy in New Hampshire for patients aged more than 50 years was
      approximately twice the available capacity. However, if the assessed screening
      capacity of 2002 were to increase by 20%, combined with a target of 60%
      population compliance with screening as an initial goal, the demand for
      colonoscopy in New Hampshire would be met.

PMID- 17184963
TI  - From health destruction to health promotion: conversion of a worksite smoking
      shelter.

PMID- 17184964
TI  - Health literacy and health risk behaviors among older adults.
AB  - BACKGROUND: Limited health literacy is associated with poorer physical and mental
      health, although the causal pathways are not entirely clear. In this study, the
      association between health literacy and the prevalence of health risk behaviors
      was examined among older adults. METHODS: A cross-sectional survey of 2923 new
      Medicare, managed-care enrollees was conducted in four U.S. metropolitan areas
      (Cleveland OH; Houston TX; Tampa FL; Fort Lauderdale-Miami FL). Health literacy
      was measured using the short form of the Test of Functional Health Literacy in
      Adults. Behaviors investigated included self-reported cigarette smoking, alcohol
      consumption, physical activity, body mass index, and seat belt use. RESULTS:
      Individuals with inadequate health literacy were more likely to have never smoked
      (46.7% vs. 38.6, p =0.01); to completely abstain from alcohol (75.6% vs. 57.9, p
      <0.001); and to report a sedentary lifestyle (38.2% vs. 21.6%, p <0.001) compared
      to those with adequate health literacy. No significant differences were noted by
      mean body mass index or seat belt use. In multinomial logistic regression models
      that adjusted for relevant covariates, inadequate health literacy was not found
      to be significantly associated with any of the health risk behaviors
      investigated. CONCLUSIONS: Among community-dwelling elderly, limited health
      literacy was not independently associated with health risk behaviors after
      controlling for relevant covariates.

PMID- 17184965
TI  - Do anti-tumor necrosis factors induce response and remission in patients with
      acute refractory Crohn's disease? A systematic meta-analysis of controlled
      clinical trials.
AB  - To determine whether anti-tumor necrosis factors induce clinical response and
      remission in patients with Crohn's disease, PUBMED, OVID, and SCOPUS databases
      were searched for studies investigated the efficacy of anti-tumor necrosis
      factors on CD. Data were collected from 1966 to 2005 (up to 31 December). Types
      of outcome investigated were response (decrease in CDAI score >/=70 points) and
      remission (CDAI score </=150 points) 2 and 4 weeks after drug administration. The
      criteria for inclusion of studies in this analysis were exposure of patients with
      CD to any therapeutic dosage of any anti-tumor necrosis factors (infliximab,
      cetrolizumab, CDP870, CDP571, etanercept, onarcept). The results showed that anti
      tumor necrosis factors have improved only clinical response 2 weeks after
      administration of these drugs statistically, but their effects on clinical
      remission after 2 weeks and response and remission after 4 weeks have not been
      significant. It seems that anti-tumor necrosis factors are not effective for
      induction of response and remission in patients with Crohn's disease.

PMID- 17184966
TI  - Glucocorticoids co-interact with lipoxin A4 via lipoxin A4 receptor (ALX) up
      regulation.
AB  - Lipoxin A(4) (LXA(4)) is an eicosanoid which is produced via lipoxygenases and
      characteristic of its anti-inflammatory effect in many metabolites of arachidonic
      acid, which are mostly pro-inflammatory. Glucocorticoids are well known also for
      their strong anti-inflammatory action but induce 5-lipoxygenase, essential to
      synthesize leukotrienes, which are pro-inflammatory. To elucidate the interaction
      of glucocorticoids and lipoxin A(4) for anti-inflammation, we analyzed in vitro
      expression of lipoxin A(4) receptor (ALX) on human neutrophils and the in vivo
      anti-inflammatory effect of glucocorticoids and LXA(4) using a dermal
      inflammation mouse model. ALX mRNA was up-regulated by dexamethasone (Dex) in
      human neutrophils. A glucocorticoid receptor antagonist, mifepristone, suppressed
      up-regulation of ALX induced by Dex. LXA(4) and/or Dex decreased CD11b expression
      on human neutrophils and suppressed mouse dermatitis induced by LTB(4). These
      results suggest that anti-inflammatory effects of glucocorticoids depend at least
      partly on up-regulation of ALX and that the lipoxin system could be a negative
      feedback regulator for LTB(4).

PMID- 17184967
TI  - Insulin resistance and low urinary citrate excretion in calcium stone formers.
AB  - Epidemiological data suggest an association between kidney stones and some
      features of metabolic syndrome such as an overweight condition, arterial
      hypertension or glucose intolerance. However, mechanisms remain to be elucidated.
      This study aimed to evaluate insulin resistance, as assessed by homeostasis model
      assessment (HOMA-IR), and urine composition analysis in patients affected by
      calcium nephrolithiasis. A cohort of 61 (38 male, 29-57 years of age) non
      diabetic calcium stone formers was studied. Data about body mass index, arterial
      blood pressure, serum biochemistry including parathyroid hormone and calcitriol
      were recorded in all the patients; fasting glucose and insulin were determined to
      calculate HOMA-IR value and accordingly the patients were grouped into tertiles.
      Urine pH and urinary excretion of calcium, citrate, phosphate, oxalate, uric
      acid, urea and creatinine were measured on 24h urine samples. Patients of the
      highest HOMA-IR tertile showed lower urine citrate levels than patients of the
      lowest HOMA-IR tertile (475+/-243 vs. 630+/-187 mg/24h, p<0.05), whereas no
      difference was detected as far as urinary oxalate, calcium, uric acid, phosphate,
      and urine pH and urine volume output were concerned. HOMA-IR values were
      positively related to uric acid serum levels (r=0.31, p<0.05) and negatively to
      urinary citrate excretion (r=-0.26, p<0.05). Hypocitraturic patients showed
      higher levels of HOMA-IR than normocitraturic ones (3.03+/-0.92 vs. 2.25+/-1.19,
      p<0.05). This study shows that a higher level of insulin resistance is associated
      with lower urinary citrate excretion, and that hypocitraturic patients show a
      greater insulin resistance than normocitraturic calcium stone formers. This may
      be related to changes in citrate, Na(+)-K(+) and H(+) renal tubule transports,
      which have been described in insulin resistance. In conclusion, insulin
      resistance may contribute to an increased risk of calcium stone formation by
      lowering urinary citrate excretion. This finding suggests the need for a careful
      metabolic assessment in patients known to form calcium stones in order to ensure
      stone recurrence prevention and cardiovascular protection.

PMID- 17184968
TI  - Changes in implicit associations do not occur simultaneously to Pavlovian
      conditioning of physiological anxiety responses.
AB  - Previous research shows that an 'angry face' conditioned stimulus will elicit
      conditioned skin conductance responses (SCR) after a small number of trials
      pairing it with a mild electric shock. Such conditioning occurs even with masked
      presentations of the facial stimulus. Furthermore, the Implicit Association Test
      (IAT) has been demonstrated to be sensitive to the presence of information
      processing biases seen in specific phobias. We examined the ability of the IAT to
      detect changes in implicit associations that arise from pairing one facial image
      (CS+) with a mild electro-tactile stimulation whereas a second facial image (CS-)
      was presented alone. Participants (N=117) were assigned to one of four groups: a
      group that received no shocks with unmasked presentation of the facial images; a
      group that received no shocks with masked presentation; a group with shocks
      delivered simultaneously to the masked presentation of the CS+; and a group that
      received shocks simultaneous to unmasked CS+ presentation. Learning was assessed
      through both SCR and the IAT. Results showed that while it was possible to
      condition a SCR to the CS+, this learning was not detectable using the IAT.
      Implications of the discrepancies in the outcome measures are discussed.

PMID- 17184969
TI  - The effectiveness of Teratology Information Services (TIS).
AB  - BACKGROUND: Women and their health care providers have few reliable sources of
      information regarding the safety of exposures in pregnancy and lactation.
      Evidence-based information on these topics is provided by Teratology Information
      Services (TIS). Access to TIS, however, is limited in many regions, and many
      services have difficulty maintaining ongoing funding. The objective of this
      review is to highlight published reports of the effectiveness of TIS in improving
      maternal and neonatal health. METHODS: A search of the Pub Med and Econ Lit
      databases was performed with no date restriction, using the search terms
      teratology, information, counseling, pregnancy, effectiveness, birth defects.
      RESULTS: Information disseminated from TIS has been shown to prevent congenital
      malformations, unnecessary pregnancy terminations, and occupational risks. TIS
      support optimal nutritional supplementation in pregnancy and optimal drug therapy
      in pregnancy and breast-feeding. In addition, they correct misperceptions of risk
      and facilitate knowledge transfer and translation. TIS have the potential to
      provide health care cost savings. CONCLUSIONS: TIS are vital services in
      supporting optimal maternal and neonatal health. A formal economic evaluation of
      TIS is required in order to inform resource allocation decision-making and
      continued funding of these services.

PMID- 17184970
TI  - Metronidazole-induced alterations in murine spermatozoa morphology.
AB  - The aim of this work was to assess the effect of metronidazole (MTZ) on the
      stages of the seminiferous epithelial cycle and spermatozoa morphology when the
      drug is administered in human therapeutic doses to 60-day-old CFW male mice. The
      frequency of the stages was established by counting spermatocytes in pachytene
      and spermatids. Abnormalities in the flagellum or the head, lack of maturity and
      multiple malformations, were considered in the morphological analysis. Murine
      control strain was compared with MTZ treated group (v.ip 130 mg/kg/bw) both kept
      in standard captivity conditions. Cellular composition or number of stages in the
      seminiferous tubules were not altered in MTZ exposed animals, though the number
      of cells in stages I, V and XII was increased. The sperm cell morphology was
      severely affected by the treatment with potentially serious consequences on the
      normal fertilization process. Thus, the MTZ has to be considered as a conceivable
      thread regarding male fertility.

PMID- 17184972
TI  - Adolescent nicotine exposure produces less affective measures of withdrawal
      relative to adult nicotine exposure in male rats.
AB  - Vulnerability to nicotine addiction is significantly increased in individuals who
      begin smoking during adolescence; however, the underlying mechanisms of this
      phenomenon remain unclear. This study examined the motivational effects of
      nicotine withdrawal in adolescent (PND 27-42) and adult (PND 60-75) rats using
      the conditioned place aversion paradigm. Male Wistar rats were tested for their
      initial preference for either of two distinct compartments of our conditioning
      apparatus. Rats were then implanted with subcutaneous (sc) pumps that produce
      equivalent blood plasma levels of nicotine for 14 days. Conditioning was
      conducted over the last 8 days of nicotine exposure. Rats received the nicotinic
      antagonist mecamylamine (1.5 or 3.0 mg/kg, sc) to precipitate withdrawal in their
      initially preferred compartment, and on alternate days they received saline in
      their non-preferred compartment. Following conditioning, rats were re-tested for
      their preference for each compartment. A subsequent study was conducted to
      examine potential developmental differences in learning place aversion produced
      by another aversive stimulus, lithium chloride (LiCl). Rats received LiCl (0, 10,
      30, or 100 mg/kg, sc) in their initially preferred side using similar
      conditioning procedures. Adults displayed robust place aversion produced by
      nicotine withdrawal. This effect was lower in adolescent rats even in a group of
      young rats that received 7 additional days of nicotine exposure prior to
      conditioning. This developmental difference was specific to nicotine withdrawal
      since there were no differences between adolescents and adults in learning place
      aversion with LiCl. Our findings demonstrating reduced effects of nicotine
      withdrawal constitute a powerful basis for the increased vulnerability to
      nicotine dependence during adolescence.

PMID- 17184973
TI  - PLCgamma is enriched on poly-phosphoinositide-rich vesicles to control nuclear
      envelope assembly.
AB  - Nuclear envelope assembly is an essential event in each cell cycle but the
      proteins and lipids involved in its regulation remain mostly unknown. Assembly
      involves membrane fusions but neither specific SNAREs nor Rab GTPases have been
      identified in its control. We report that a precursor membrane population (MV1)
      required for NE assembly has a unique lipid composition consisting prominently of
      poly-phosphatidylinositides. The lipid composition was determined by adapting
      HPLC electrospray ionisation tandem mass spectrometry to phosphoinositide
      analysis, revealing the capacity of this technique to document dynamic lipid
      transitions of functional importance in natural membrane populations. MV1 is >100
      fold enriched in endogenous PLCgamma and >25-fold enriched in the PLC substrate
      phosphatidylinositol bisphosphate (PtdInsP2) compared to the second membrane
      population, derived largely from endoplasmic reticulum (ER), that contributes
      most of the NE. During NE formation PLCgamma becomes transiently phosphorylated
      at the tyrosine 783 site indicative of its activation. In addition specific
      inhibition of PLCgamma blocks nuclear envelope formation. In vivo, PLCgamma is
      concentrated on vesicles of similar size to purified MV1. These associate with
      nuclei during the period of NE formation and are distinct from ER membranes. The
      unprecedented concentration of PLCgamma and its substrate PtdInsP2 in a subset of
      membranes that binds to only two regions of the nucleus, and activation of
      PLCgamma by GTP during initial stages of NE formation provide a mechanism for
      temporal control of NE assembly and offer an explanation for how such a process
      of membrane fusion can be spatially regulated.

PMID- 17184974
TI  - Topographical CT-data analysis of the human orbital floor.
AB  - The aim of this study was to evaluate the topographical anatomy of the human
      orbital floor for the production of prefabricated implants on the basis of
      computer tomography data. A database of 279 CT scans of Caucasian patients
      without traumatic deformation of the midface was analysed. 3D-image segmentation
      of the midfacial skeleton was performed using a computer-assisted protocol. A
      virtual plane (50 x 50 mm (2)) was constructed using defined landmarks above the
      orbital floor. An automated procedure was used to measure the distance between
      the orbital floor and the constructed plane at 400 distinct points. A
      mathematical algorithm was used to analyse the data, and to calculate a map of
      the orbital floor. Statistical analysis of the data revealed that orbital floor
      topography could be classified as distinct clusters. There were 12 variations of
      orbital floor anatomy: three unique patterns of the orbital floor for the right
      orbit and three corresponding patterns for the left side, all of which varied
      between the sexes. The 12 patterns were constructed with a statistical confidence
      interval of 1.36+/-0.6mm.

PMID- 17184971
TI  - Cocaine during adolescence enhances dopamine in response to a natural reinforcer.
AB  - The use of cocaine during adolescent development could alter the normal growth of
      brain regions affected by cocaine, specifically the reward system, and impact the
      adult mesolimbic system. However, there is scant literature aimed at determining
      whether animals are more vulnerable to the adverse effects of drugs during
      adolescence. The present study investigated whether cocaine pretreatment in
      either adolescence or adulthood altered the dopaminergic response to a naturally
      reinforcing substance in adulthood. To evaluate the responsivity of the
      mesolimbic system after repeated cocaine, sucrose was offered during the dialysis
      procedure and dialysates were collected. Regardless of age all saline pretreated
      rats had significant increases in sucrose-induced extracellular dopamine (DA)
      levels in the nucleus accumbens septi (NAcc) as compared to baseline levels. Rats
      pretreated with cocaine as adults also had significant increases in DA levels
      after sucrose. Interestingly, sucrose intake significantly enhanced DA levels in
      cocaine pretreated adolescent rats as compared to all other conditions. The
      results from the present study show that in rats pretreated with cocaine during
      adolescence there is an enhanced response of the dopaminergic system in animals
      exposed to a naturally reinforcing substance. Therefore, cocaine exposure during
      adolescence results in long-term functional changes in the mesolimbic pathway.
      Future studies need to ascertain the underlying mechanisms and their potential
      role in cocaine addiction.

PMID- 17184975
TI  - What can be learnt from the natural history of anxiety disorders?
AB  - BACKGROUND: There is insufficient knowledge of the long-term course of panic
      disorder (PD). AIM: To determine the long-term course and prognostic variables in
      patients diagnosed with PD. METHODS: Patients who were diagnosed of anxiety
      states between 1950 and 1961, were examined using a structured clinical interview
      (SCID-DSM-III-R) between 1984 and 1988 (n=144). A re-examination was performed in
      the period 1997-2001 (N=125). Mean length of follow-up from onset was 47 years.
      RESULTS: PD tends to be chronic. Among those who recovered, 93% had done so
      already by the 1980s. Lack of regular treatment compliance, progression to
      agoraphobia and number of episodes of panic disorder were associated with worse
      outcome. Agoraphobia without panic attacks and somatization symptoms were the
      most prevalent clinical status at follow-up. CONCLUSION: After several decades,
      participants improve with regard to number of panic attacks, though most continue
      to have residual symptoms.

PMID- 17184976
TI  - Functioning of oxidative phosphorylation in liver mitochondria of high-fat diet
      fed rats.
AB  - We proposed that inhibition of mitochondrial adenine nucleotide translocator
      (ANT) by long chain acyl-CoA (LCAC) underlies the mechanism associating obesity
      and type 2 diabetes. Here we test that after long-term exposure to a high-fat
      diet (HFD): (i) there is no adaptation of the mitochondrial compartment that
      would hinder such ANT inhibition, and (ii) ANT has significant control of the
      relevant aspects of oxidative phosphorylation. After 7 weeks, HFD induced a 24+/
      6% increase in hepatic LCAC concentration and accumulation of the oxidative
      stress marker N(epsilon)-(carboxymethyl)lysine. HFD did not significantly affect
      mitochondrial copy number, oxygen uptake, membrane potential (Deltapsi), ADP/O
      ratio, and the content of coenzyme Q(9), cytochromes b and a+a(3). Modular
      kinetic analysis showed that the kinetics of substrate oxidation,
      phosphorylation, proton leak, ATP-production and ATP-consumption were not
      influenced significantly. After HFD-feeding ANT exerted considerable control over
      oxygen uptake (control coefficient C=0.14) and phosphorylation fluxes (C=0.15),
      extra- (C=0.23) and intramitochondrial (C=-0.56) ATP/ADP ratios, and Deltapsi (C=
      0.11). We conclude that although HFD induces accumulation of LCAC and N(epsilon)
      (carboxymethyl)lysine, oxidative phosphorylation does not adapt to these
      metabolic challenges. Furthermore, ANT retains control of fluxes and
      intermediates, making inhibition of this enzyme a more probable link between
      obesity and type 2 diabetes.

PMID- 17184977
TI  - Normal pituitary volumes in chronic schizophrenia.
AB  - Pituitary volumes were shown to be abnormally large in pre- or first-psychotic
      episode patients and abnormally reduced in established schizophrenia by magnetic
      resonance imaging (MRI) studies. We present here the results of the second ever
      published MRI study exploring pituitary size in a large population of patients
      with chronic schizophrenia recruited from the geographically defined catchment
      area of South Verona, Italy. No significant differences for pituitary volumes
      were reported between 65 subjects with chronic schizophrenia and 65 normal
      individuals (mean age+/-S.D.=42.31+/-11.44 and 40.54+/-11.12 years). In contrast
      to Pariante et al. (2004), normal pituitary size was found in our population of
      chronic schizophrenia. Discrepancies between these two studies may partially be
      accounted by sample age and gender. Considering increased pituitary volumes in
      pre- or first-psychotic episode patients, we put forward the hypothesis that
      pituitary size may normalize or reduce with the progression of the illness as a
      result of reduced numbers of acute episodes and consequent diminished
      hypothalamus-pituitary-adrenal axis activity. To better test this hypothesis,
      future large MRI studies should investigate pituitary volumes in chronic
      schizophrenia longitudinally, also collecting pituitary hormones and cortisol,
      and comparing the effects of typical and atypical antipsychotics on pituitary
      size in a randomized trial.

PMID- 17184978
TI  - Emotional words induce enhanced brain activity in schizophrenic patients with
      auditory hallucinations.
AB  - Neuroimaging studies of emotional response in schizophrenia have mainly used
      visual (faces) paradigms and shown globally reduced brain activity. None of these
      studies have used an auditory paradigm. Our principal aim is to evaluate the
      emotional response of patients with schizophrenia to neutral and emotional words.
      An auditory emotional paradigm based on the most frequent words heard by
      psychotic patients with auditory hallucinations was designed. This paradigm was
      applied to evaluate cerebral activation with functional magnetic resonance
      imaging (fMRI) in 11 patients with schizophrenia with persistent hallucinations
      and 10 healthy subjects. We found a clear enhanced activity of the frontal lobe,
      temporal cortex, insula, cingulate, and amygdala (mainly right side) in patients
      when hearing emotional words in comparison with controls. Our findings are
      consistent with other studies suggesting a relevant role for emotional response
      in the pathogenesis and treatment of auditory hallucinations.

PMID- 17184979
TI  - Effect of salts on the electrical conductance of a fluorine-containing
      poly(carboxylic acid), PPFNA.
AB  - Electrical conductance and other solution properties of aqueous solutions of a
      fluorine-containing poly(carboxylic acid), (poly(9H,9H-perfluoro-2,5-dimethyl-3,6
      dioxa-8-nonenoic acid), PPFNA) were studied with special attention to the salt
      effect. This polymer dissociated strongly resulting in a low pH value in
      unneutralized state (beta=0, beta: degree of neutralization). The specific
      conductance was the highest at beta=0 and decreased as beta increased. A
      considerable increase in conductance was observed by titrating NaCl at low beta,
      because large amounts of bound protons were released by addition of NaCl. The
      amounts of released protons exceeded those originally dissociated at beta=0. Such
      an anomalous proton liberation suggests that this polymer is a fairly strong
      polyacid but not a typical one such as poly(styrene sulfonic acid). Under fully
      neutralized state (beta=1), however, the solution conductance was lower than the
      sum of the polymer and NaCl added, due to polyion-salt ion interaction.

PMID- 17184980
TI  - [Potential for reduced intensity conditioning regimens for paediatric
      malignancies].

PMID- 17184981
TI  - Pelargonium sidoides preparation (EPs 7630) in the treatment of acute bronchitis
      in adults and children.
AB  - Acute bronchitis, although mostly caused by viral infections, is commonly treated
      with antibiotics. As antibiotics should only be prescribed upon strict
      indication, treatment options like a liquid herbal drug preparation from the
      roots of Pelargonium sidoides (EPs 7630) gain more and more interest. To evaluate
      the efficacy and safety of treatment with EPs 7630 in patients with acute
      bronchitis, a multi-centre, prospective, open observational study was conducted
      in 440 study sites located in Germany. A total of 2099 patients aged 0-93 years
      with productive cough for less than six days without indication for treatment
      with antibiotics were given EPs 7630-solution in an age-dependent dosage for 14
      days. The primary outcome criterion was the mean change of the Bronchitis
      Severity Score (BSS: cough, sputum, rales/rhonchi, chest pain at cough, dyspnoea)
      from baseline to patient's individual last observation. During treatment, the
      mean BSS of all patients decreased from 7.1+/-2.9 points at baseline to 1.0+/-1.9
      points at patients' individual last visit. Subgroup analysis for children showed
      a decrease of mean BSS from 6.3+/-2.8 points to 0.9+/-1.8 points and analysis of
      children younger than three years showed a decrease of mean BSS from 5.2+/-2.5
      points to 1.2+/-2.1 points. Adverse events occurred in 26/2099 (1.2%) patients.
      Serious adverse events were not reported. In conclusion, EPs 7630 is an effective
      and well tolerated treatment of acute bronchitis in adults, children and infants
      outside the strict indication for antibiotic treatment.

PMID- 17184982
TI  - Treatment effect and safety of EPs 7630-solution in acute bronchitis in
      childhood: report of a multicentre observational study.
AB  - An open post-marketing surveillance study was conducted to examine the treatment
      effect and safety of EPs 7630-solution in the treatment of acute bronchitis in
      children. This study included a total of 742 children (aged between 0 and 12
      years) with acute bronchitis (83.4%) or acute exacerbations of chronic bronchitis
      (14.3%), who were treated with different doses of the herbal drug for up to 14
      days. Five bronchitis specific symptoms (BSS) were summed up to give an overall
      measure of disease severity. Non-specific disease symptoms (loss of appetite,
      diarrhoea, headache, vomiting, and fever) were also recorded, together with
      adverse events and overall ratings of efficacy and tolerability. The overall BSS
      score decreased during treatment from 6.0+/-3.0 points at baseline to 2.7+/-2.5
      points after 7 days and to 1.4+/-2.1 points after 14 days. Remission or
      improvement in at least 80% of patients was recorded for all the individual
      component symptoms. The proportion of patients suffering from non-specific
      symptoms also substantially improved during treatment. For example, loss of
      appetite was present in 65.8% of patients at study begin, but only in 27.6% at
      the time point of last observation visit. In 88.3% of cases, the responsible
      physician rated the treatment as successful. Adverse events were minor and
      transitory. In conclusion, EPs 7630-solution was shown to be a safe and an
      effective treatment option for acute bronchitis or acute exacerbations of chronic
      bronchitis in children.

PMID- 17184983
TI  - Extract of Pelargonium sidoides (EPs 7630) improves phagocytosis, oxidative
      burst, and intracellular killing of human peripheral blood phagocytes in vitro.
AB  - Clinical data show that EPs 7630, an aqueous ethanolic extract from the roots of
      Pelargonium sidoides, can be used for the treatment of upper respiratory tract
      infections (URTI). The biological effects of the preparation have not been fully
      investigated. The objective of this study was to examine the impact of EPs 7630
      on the activity of human peripheral blood phagocytes (PBP). A whole blood-based,
      flow cytometric assay was used to simultaneously assess phagocytosis and
      oxidative burst. Calcein-AM stained Candida albicans (DSM 1386) were used as
      target organisms. Oxidative burst was measured by addition of dihydroethidium
      (DHE). Target organisms and whole blood were co-incubated and analyzed after 0,
      2, 4, 6, 10, and 30 min. Intracellular killing of the target organisms was
      evaluated by determining the number of surviving yeast cells after co-incubation
      of C. albicans and human whole blood. EPs 7630 was applied in therapeutically
      relevant concentrations between 0 and 30 microg/ml. Compared with controls EPs
      7630 increased the number of phagocytosing PBP during the observed time points
      between 2 and 10 min in a concentration-dependent manner, with a maximum
      enhancement of 56% at 2 min (p=0.002). The application of EPs 7630 also led to a
      significant increase in the number of burst-active PBP for all time points
      observed beyond 2 min (p<0.001). The maximum augmentation was 120% after
      application of 30 microg/ml EPs 7630 at 4 min. Using a microbiological assay,
      intracellular killing was also enhanced by EPs 7630. This was expressed by a
      significant reduction in the number of surviving target organisms (p<0.001). The
      maximum reduction in viable yeast cells (-31%) was observed after co-incubation
      for 120 min with the highest concentration of EPs 7630 (30 microg/ml). In
      conclusion, the positive effects of EPs 7630 on phagocytosis, oxidative burst,
      and intracellular killing of yeast cells as test organisms are important
      components of the compound's biological activity. Our findings constitute a
      valuable contribution to understanding the clinical effects of EPs 7630.

PMID- 17184984
TI  - EPs 7630-solution--an effective therapeutic option in acute and exacerbating
      bronchitis.
AB  - Acute bronchitis is one of the most common diagnoses in ambulatory care medicine.
      Although the benefit of antibiotics for acute bronchitis, which is mostly virally
      induced, is disputed, they are often prescribed. A therapeutic option for
      respiratory tract infections that do not fall within the strict indication range
      for antibiotic administration is the liquid herbal drug preparation from the
      roots of Pelargonium sidoides, EPs 7630 (Umckaloabo), which has been tested
      against placebo in double-blind clinical trials. EPs 7630 has both antibacterial
      and immuno-modulating properties. The efficacy and tolerability of EPs 7630 was
      investigated in a prospective, open, multicentric outcomes study with 205
      patients suffering from acute bronchitis or acute exacerbation of chronic
      bronchitis. The main outcome measure was the change in the total score of five
      symptoms typical for bronchitis (cough, expectoration, wheezing/whistling on
      expiration, chest pain during coughing, and dyspnoea), which were each rated
      using a 5-point scale (from 0=not present to 4=extremely pronounced). Further
      symptoms (hoarseness, headache, aching limbs and fatigue) were assessed using a
      four-point scale (from 0=not present to 3=very pronounced). The total score of
      the typical bronchitis symptoms amounted to 6.1+/-2.8 points on average at the
      start of treatment and decreased by 3.3+/-3.8 points to 2.8+/-2.6 points by the
      final examination on day 7. About 60.5% of the patients assessed their health
      condition at the end of the study as much improved or free from symptoms. The
      onset of action appeared after two days on average. Adverse events occurred in a
      total of 16 patients. There were no serious adverse events. Altogether, 78% of
      the patients were satisfied or very satisfied with the treatment.

PMID- 17184985
TI  - Integrins and the actin cytoskeleton.
AB  - The ability to connect to the actin cytoskeleton is a key part of the adhesive
      function of integrins. This linkage between integrins and the cytoskeleton
      involves a large complex of integrin-associated proteins that function in both
      the assembly and disassembly of the link. Genetic evidence has helped to clarify
      the relative contributions of different components of this link. In different
      contexts integrins can either stimulate or suppress actin based structures,
      indicating the variety of pathways leading from integrins to the cytoskeleton.
      The cytoskeleton also contributes to the extent of the integrin junction,
      allowing an adhesive contact to attain sufficient strength to resist contractile
      forces involved in cellular movement and function.

PMID- 17184986
TI  - Microtubule polymerases and depolymerases.
AB  - The variety of shapes and sizes of the microtubule cytoskeleton is as great as
      the number of different cell types. This large variety is a consequence of the
      dynamic properties of microtubules, which allow them to adopt distributions of
      arbitrary size and form. How is the distribution of microtubule lengths
      controlled? Recent work suggests that the length distribution is controlled, at
      least in part, by the activity of microtubule polymerases and depolymerases,
      which accelerate microtubule growth and shrinkage. Specifically, biochemical and
      single-molecule studies have shown how MCAK (kinesin-13) and Kip3p (kinesin-8)
      accelerate depolymerization and how XMAP215 may accelerate growth. Studies on the
      yeast Dam1 complex have shown how proteins can couple a cellular structure, the
      kinetochore, to the ends of polymerizing and depolymerizing microtubules.

PMID- 17184987
TI  - Reconstituted expression of menin in Men1-deficient mouse Leydig tumour cells
      induces cell cycle arrest and apoptosis.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome caused by the
      inactivation of the responsible gene, MEN1. To date, the lack of MEN1-deficient
      cell lines derived directly from MEN1 tumours has hampered the detailed study of
      the MEN1 gene. We have established several stable Men1-deficient Leydig cell
      tumour (LCT) lines derived from a Leydig cell tumour developed in a male
      heterozygous Men1 mutant mouse. Our data show that these cell lines maintain the
      basic characteristics of Leydig cells in terms of both androgen synthesis and
      gene expression. Interestingly, reconstituted menin expression in one of Men1
      deficient LCT cell lines resulted in cell growth inhibition, suggesting that the
      function of cell growth suppression of the menin pathway, apart from menin
      itself, is essentially preserved in these cells. Furthermore, we show that menin
      re-expression in these Men1-deficient cells leads to a block in the transition
      from G0/G1 to S phase of the cell cycle and an increase in apoptosis, accompanied
      by a marked increase of p18INK4C and p27Kip1 expression. The current study
      therefore highlights the importance of menin expression in cell cycle and cell
      survival control in endocrine cells, and may provide insights into the mechanisms
      of tumour suppression by menin in related endocrine tumours.

PMID- 17184990
TI  - Conservative surgery for well-differentiated liposarcomas of the extremities
      adjacent to major neurovascular structures.
AB  - BACKGROUND: There is no clear consensus as to the appropriate nomenclature and
      the best surgical strategy for well-differentiated liposarcomas. A wide surgical
      excision is recommended over marginal resection for local control of well
      differentiated liposarcomas. However, this surgical procedure should be
      reconsidered for lesions, which come into contact with major neurovascular
      structures. METHODS: Between 1998 and 2004, 12 well-differentiated liposarcomas
      of the extremities were treated at our institute. Among them, nine lesions (75%)
      adjacent to major nerves or blood vessels were marginally resected with careful
      dissection of these critical structures. The clinical outcomes were reviewed for
      a mean follow-up time of 4 years. RESULTS: Seven patients continued to be disease
      free without any loss of limb function. One patient developed a local recurrence
      30 months postoperatively. The other patient with a foot lesion involving the
      fourth metatarsal bone has experienced slight difficulty in gait-balancing due to
      the fourth toe amputation, but remains free of disease. The local control rate
      was 88.9%, even though seven lesions were resected with positive surgical
      margins. CONCLUSIONS: Our findings suggested that well-differentiated
      liposarcomas frequently arise in close proximity to major nerves or blood
      vessels. Marginal resection alone seems to be adequate for these lesions to
      preserve critical structures.

PMID- 17184989
TI  - Diagnosis and management of metastatic spine disease.
AB  - Spinal metastases are a significant source of morbidity in patients with systemic
      cancer. Roughly 30% of patients with cancer develop symptomatic spinal metastases
      during the course of their illness, and up to 90% of cancer patients possess
      metastatic lesions within the spine at the time of death with advances in the
      treatment of systemic disease, survival in such patients has increased. This
      factor combined with improved imaging modalities will undoubtedly increase the
      incidence in which spinal metastases are encountered by physicians. In this
      review, the authors not only attempt to present the myriad ways in which patient
      with spinal metastases present, but also the means by which they are currently
      diagnosed and managed. In addition, we propose a simple algorithm to aid in
      deciding which patients are ideally treated medically and which patients may
      benefit from surgery.

PMID- 17184988
TI  - Role of protein kinase C in aldosterone-induced non-genomic inhibition of
      basolateral potassium channels in human colonic crypts.
AB  - Aldosterone produces rapid, non-genomic, inhibition of basolateral intermediate
      conductance K(+) (IK(Ca)) channels in human colonic crypt cells but the
      intracellular second messengers involved are unclear. We therefore evaluated the
      role of protein kinase C (PKC) in aldosterone's non-genomic inhibitory effect on
      basolateral IK(Ca) channels in crypt cells from normal human sigmoid colon. Patch
      clamp studies revealed that in cell-attached patches, IK(Ca) channel activity
      decreased progressively to 38+/-8% (P<0.001) of the basal value 10 min after the
      addition of 1 nmol/L aldosterone, and decreased further to 23+/-6% (P<0.02) of
      the basal value 5 min after increasing the aldosterone concentration to 10
      nmol/L. Pre-incubation of crypts with 1 micromol/L chelerythrine chloride or 1
      micromol/L Go 6976 (PKC inhibitors) prevented the inhibitory effect of
      aldosterone. Conversely, channel activity decreased to 60+/-9% (P<0.02) of the
      basal value 10 min after the addition of 500 nmol/L PMA (a PKC activator),
      whereas 4alpha-PMA (an inactive ester) had no effect. When aldosterone (10
      nmol/L) and PMA were added together, IK(Ca) channel activity was inhibited to the
      same extent as with aldosterone alone. These results indicate that aldosterone's
      non-genomic inhibitory effect on the macroscopic basolateral K(+) conductance in
      human colonic crypts reflects PKC-mediated inhibition of IK(Ca) channels.

PMID- 17184991
TI  - Comparison of polynomial and neural fuzzy models as applied to the ethanolamine
      pulping of vine shoots.
AB  - The influence of operational variables in the pulping of vine shoots by use of
      ethanolamine [viz. temperature (155-185 degrees C), cooking time (30-90min) and
      ethanolamine concentration (50-70% v/v)] on the properties of the resulting pulp
      (viz. yield, kappa index, viscosity and drainability) was studied. A central
      composite factorial design was used in conjunction with the software BMDP and
      ANFIS Edit Matlab 6.5 to develop polynomial and fuzzy neural models that
      reproduced the experimental results of the dependent variables with errors less
      than 10%. Both types of models are therefore effective with a view to simulating
      the ethanolamine pulping process. Based on the proposed equations, the best
      choice is to use values of the operational valuables resulting in near-optimal
      pulp properties while saving energy and immobilized capital on industrial
      facilities by using lower temperatures and shorter processing times. One
      combination leading to near-optimal properties with reduced costs is using a
      temperature of 180 degrees C and an ethanolamine concentration of 60% for 60min,
      to obtain pulp with a viscosity of 6.13% lower than the maximum value (932.8ml/g)
      and a drainability of 5.49% lower than the maximum value (71 (o)SR).

PMID- 17184992
TI  - Molecular chaperones and protein kinase quality control.
AB  - The Hsp90-Cdc37 chaperone pair has special responsibility for folding of protein
      kinases. This function has made Hsp90 a target for new chemotherapeutic
      approaches, and several compounds are currently being tested for their ability to
      inhibit many different kinases simultaneously. Not all kinases are sensitive to
      these inhibitors, however, and this difference might depend on how each kinase
      interacts with Hsp90 and Cdc37 during folding of the nascent chain and
      thereafter. Indeed, several kinases require the persistent presence of both
      chaperones after initial folding and some of these kinases seem to be
      particularly sensitive to Hsp90 inhibitors. This requirement might relate to
      conformational changes that take place during the protein kinase activity cycle.

PMID- 17184993
TI  - Importance of widespread gene transfer agent genes in alpha-proteobacteria.
AB  - The gene transfer agent produced by Rhodobacter capsulatus (RcGTA) is a model for
      several virus-like elements that seem to function solely for mediating gene
      exchange. Several genes that encode RcGTA are clearly related to bacteriophage
      genes but the cellular regulatory mechanisms that control RcGTA production
      indicate that RcGTA is more than just a defective prophage. Genome sequencing
      projects show that seemingly functional RcGTA-like structural gene clusters are
      present in many other species of alpha-proteobacteria, which might also produce
      RcGTA-like particles. Here, we use the genomic sequence data that are currently
      available to identify candidate GTA-producing species and propose an evolutionary
      scheme for RcGTA-like elements in the alpha-proteobacteria.

PMID- 17184995
TI  - Beneficial effects of rolipram in a quinolinic acid model of striatal
      excitotoxicity.
AB  - Activity of c-AMP responsive element-binding protein (CREB) is decreased in
      Huntington's disease (HD). Such decrease was also described by our group in the
      quinolinic acid lesion model of striatal excitotoxicity. The phosphodiesterase
      type IV inhibitor rolipram increases CREB phosphorylation. Such drug has a
      protective effect in global ischaemia and embolism in rats. In this study, we
      sought to determine whether rolipram displays a neuroprotective effect in our rat
      model of HD. Animals were surgically administered QA and subsequently treated
      with rolipram daily up to 2 and 8 weeks respectively. After these time points,
      rats were sacrificed and immunohistochemical studies were performed in the
      striata. In the rolipram-treated animals, striatal lesion size was about 62%
      smaller that in the vehicle-treated ones at 2 weeks time point. Moreover, the
      surviving cell number was several times higher in the rolipram-treated animals
      than in the vehicle group at both time points. Rolipram also showed to be
      effective in increasing significantly the levels of activated CREB in the
      striatal spiny neurons, which accounts mostly for its beneficial effect in our
      rodent model of excitotoxicity. Our findings show that rolipram could be
      considered as a valid therapeutic approach for HD.

PMID- 17184996
TI  - Prognostic factors for long-term survival in patients with thoracic metastatic
      disease: a 10-year experience.
AB  - OBJECTIVE: To compare survival results after resection in patients with thoracic
      parenchymal metastatic disease versus non-parenchymal metastatic disease and to
      identify prognostic factors for survival. METHODS: From 1990 to 2002, we
      retrospectively studied 134 procedures performed on 93 patients (3-84 years old).
      There were 73 patients with parenchymal resection and 20 patients with non
      parenchymal resection. Tumor histology was epithelial in 62 patients, sarcoma in
      21 patients, and teratomas and melanoma in 6 and 4 patients, respectively. Sixty
      five patients underwent a metastasectomy once, whereas 28 had their metastatic
      disease repeatedly resected. RESULTS: Follow-up was 100% complete with a mean
      time of 43 months (range 1-169). In-hospital mortality was 2.2% (3/134
      procedures) and major morbidity 5.5%. Median survival was 39 months (95% CI: 21
      56 months). Overall, the actuarial survival at 1, 3, and 5 years were 84%, 55%,
      and 44%, respectively. For the entire group, by univariate analysis, among the 13
      predictor variables selected, only the number of metastases (Hazard Ratio
      (HR)=3.4 [95% CI: 1.9-6.1]) and completeness of resection (HR=2.3 [95% CI: 1.3
      4.2]) were found to be significant for death whereas repeated metastasectomy was
      found to be a significant predictor for survival (HR=0.25 [95% CI: 0.12-0.55]).
      In the group of parenchymal metastatic disease, a size greater than 3cm was a
      predictor for death (HR=2 [95% CI: 1.1-3.7]). In the subgroup of patients with
      colorectal metastasis, bilateral disease was also found to be a significant
      predictor for death (HR=3.6, [95% CI: 1.2-11.1]). CONCLUSION: This study supports
      our current aggressive approach to metastatic thoracic disease. Indeed, patient's
      survival is improved while a low mortality and morbidity is achieved. The most
      beneficial impact on long-term survival is correlated to the completeness of the
      surgery whereas the increasing number and size of the metastasis inversely
      correlate with survival.

PMID- 17184997
TI  - Graft design strategies with optimum antegrade bypass flow in total arterial off
      pump coronary artery bypass.
AB  - OBJECTIVE: In arterial conduits, graft flow is one of the major determinants of
      long-term patency. We sought to delineate the effect of strategy for graft
      arrangement and design to three-vessel disease by evaluation of the dominant flow
      direction in each segment of a bypass graft. MATERIALS AND METHODS: We reviewed
      coronary angiograms of 1571 bypass grafts in 395 patients who underwent total
      arterial off-pump coronary revascularization without aortic manipulation for
      three-vessel disease since December 2000. The graft flow graded as A (antegrade),
      B (competitive), C (reverse), and O (no flow=occlusion). The current arrangement
      and design has been introduced since March 2003, and consists of the in-situ left
      internal thoracic artery (ITA) to the anterior descending artery and the
      composite I-graft of the right ITA and radial artery to the left circumflex (LCX)
      and right coronary artery (RCA) territories. Either clockwise or counterclockwise
      orientation, the I-graft was chosen to achieve a sufficient antegrade flow. Group
      I consisted of 181 patients with a single in-situ ITA as a composite Y-graft.
      Group II consisted of 214 patients with bilateral in-situ ITAs, which subdivided
      into Subgroup II-A consisted of 80 patients with bilateral in-situ ITAs until
      February 2003, and Subgroup II-B consisted of 134 patients with bilateral in-situ
      ITAs since March 2003. RESULTS: The number of distal anastomoses was 3.52+/-0.63
      in Group I, and 4.36+/-0.83 in Group II, respectively (p<0.0001). The overall
      graft patency rate was 98.6% (1549/1571), and there was no significance different
      between the groups. The rate of grade A in Group II was 863/933 (92.5%) and was
      significantly higher (p=0.049) than that of Group I 572/638 (89.7%). The rate of
      functioning bypass in Subgroup II-B was (95.8%) 568/593, and was significantly
      higher (p=0.03) than that in Subgroup II-A (92.4%) 314/340. In Subgroup II-B,
      233/268 (86.9%) of the conduits had completely grade A bypass flow, and this
      ratio was significantly higher (p=0.04) than that in Subgroup II-A (79.4%)
      127/160. CONCLUSION: Usage of bilateral ITAs and selecting the orientation of the
      I-graft to LCX and RCA branches provide maximal distal anastomotic sites with
      satisfactory graft patency rate, and simultaneously minimized the incidence of
      reverse and competitive flow.

PMID- 17184994
TI  - Two alphaherpesvirus latency-associated gene products influence calcitonin gene
      related peptide levels in rat trigeminal neurons.
AB  - Herpes simplex virus type-1 (HSV-1) initially infects mucoepithelial tissues of
      the eye and the orofacial region. Subsequently, the virus is retrogradely
      transported through the axons of the trigeminal sensory neurons. HSV-1
      establishes a life-long latent infection in these neurons, during which the
      transcription of the viral genome is silent, except for the sequences encoding
      the latency-associated transcript (LAT). To determine if HSV-1 latency might
      affect calcitonin gene-related peptide (CGRP) expression in trigeminal sensory
      neurons, we transfected primary neuronal cultures of trigeminal ganglia from rat
      embryos with plasmids expressing LAT. In the presence of Bone Morphogenetic
      Protein-7 (BMP7), CGRP was expressed in 49% of sensory neurons. However, this
      percentage was reduced to 19% in neurons transfected with LAT expressing
      plasmids. We also found that transfection of the IE63 gene of varicella-zoster
      virus (VZV) reduced the percentage of trigeminal neurons containing CGRP.
      However, the observed effect of IE63 in contrast to that of LAT was completely
      reversed by treatment of cultures with MgCl2, which indicates that the effect of
      IE63 was due to increased release of CGRP from trigeminal neurons. We provide
      here the first evidence that HSV-1 LAT decreases the level of CGRP in trigeminal
      neurons. These effects may be important for reducing the neuroinflammatory
      response, thus protecting host neuronal cells during HSV-1 latency in trigeminal
      neurons. In contrast, increased release of CGRP in the presence of IE63 protein
      may contribute to the neuralgias associated with VZV infection.

PMID- 17184998
TI  - Protective effect of Mangifera indica L. polyphenols on human T lymphocytes
      against activation-induced cell death.
AB  - Activation-induced cell death (AICD) plays an important role in maintenance of
      peripheral lymphocyte homeostasis. Reactive oxygen species (ROS) combined with
      simultaneous calcium (Ca(2+)) influx into the cytosol are required for induction
      of AICD. The extract obtained from the stem bark of Mangifera indica L. has shown
      to protect T cells from in vitro AICD. This extract is rich in polyphenolic
      compounds, the three main components of which are mangiferin (MA), catechin (C)
      and epicatechin (EC). The present study has focused on the possible contribution
      of the polyphenols MA, C and EC to the demonstrated protective effect of M.
      indica extract on in vitro human T cell AICD. Our results show that these
      polyphenols diminished the increase of intracellular ROS and free Ca(2+) induced
      by T cell receptor (TCR) triggering. In addition, these polyphenols attenuated
      AICD. Our findings suggest that the T cell survival effect of M. indica extract
      is mediated, at least in part, by its main polyphenols.

PMID- 17184999
TI  - Structure of the GMPPNP-stabilized NG domain complex of the SRP GTPases Ffh and
      FtsY.
AB  - Ffh and FtsY are GTPase components of the signal recognition particle co
      translational targeting complex that assemble during the SRP cycle to form a GTP
      dependent and pseudo twofold symmetric heterodimer. Previously the SRP GTPase
      heterodimer has been stabilized and purified for crystallographic studies using
      both the non-hydrolysable GTP analog GMPPCP and the pseudo-transition state
      analog GDP:AlF4, revealing in both cases a buried nucleotide pair that bridges
      and forms a key element of the heterodimer interface. A complex of Ffh and FtsY
      from Thermus aquaticus formed in the presence of the analog GMPPNP could not be
      obtained, however. The origin of this failure was previously unclear, and it was
      thought to have arisen from either instability of the analog, or, alternatively,
      from differences in its interactions within the tightly conscribed composite
      active site chamber of the complex. Using insights gained from the previous
      structure determinations, we have now determined the structure of the SRP GTPase
      targeting heterodimer stabilized by the non-hydrolysable GTP analog GMPPNP. The
      structure demonstrates how the different GTP analogs are accommodated within the
      active site chamber despite slight differences in the geometry of the phosphate
      chain. It also reveals a K+ coordination site at the highly conserved DARGG loop
      at the N/G interdomain interface.

PMID- 17185000
TI  - Diffeomorphic metric surface mapping in subregion of the superior temporal gyrus.
AB  - This paper describes the application of large deformation diffeomorphic metric
      mapping to cortical surfaces based on the shape and geometric properties of
      subregions of the superior temporal gyrus in the human brain. The anatomical
      surfaces of the cortex are represented as triangulated meshes. The diffeomorphic
      matching algorithm is implemented by defining a norm between the triangulated
      meshes, based on the algorithms of Vaillant and Glaunes. The diffeomorphic
      correspondence is defined as a flow of the extrinsic three dimensional
      coordinates containing the cortical surface that registers the initial and target
      geometry by minimizing the norm. The methods are demonstrated in 40 high
      resolution MRI cortical surfaces of planum temporale (PT) constructed from
      subsets of the superior temporal gyrus (STG). The effectiveness of the algorithm
      is demonstrated via the Euclidean positional distance, distance of normal
      vectors, and curvature before and after the surface matching as well as the
      comparison with a landmark matching algorithm. The results demonstrate that both
      the positional and shape variability of the anatomical configurations are being
      represented by the diffeomorphic maps.

PMID- 17185001
TI  - Neuroanatomical phenotypes in the reeler mouse.
AB  - The reeler mouse (Reln) has been proposed as a neurodevelopmental model for
      certain neurological and psychiatric conditions and has been studied by
      qualitative histochemistry and electron microscopy. Using magnetic resonance
      microscopy (MRM), we have quantitated for the first time the neuromorphology of
      Reln mice at a resolution of 21.5 microm. The neuroanatomical phenotypes of
      heterozygous and homozygous mutant Reln mice were compared to those of wild type
      (WT) littermates using morphometry and texture analysis. The cortical,
      hippocampal, and cerebellar phenotypes of the heterozygous and homozygous mutant
      Reln mice were confirmed, and new features were revealed. The Reln(rl/rl) mice
      possessed a smaller brain, and both Reln(rl/+) and Reln(rl/rl) mice had increased
      ventricles compared to WT controls. Shape differences were found between WT and
      Reln(rl/rl) brains, specifically in cerebellum, olfactory bulbs, dorsomedial
      frontal and parietal cortex, certain regions of temporal and occipital lobes, as
      well as in the lateral ventricles and ventral hippocampus. These findings suggest
      that certain brain regions may be more severely impacted by the Reln mutation
      than others. Gadolinium-based active staining demonstrated that layers of the
      hippocampus were disorganized in Reln(rl/rl) mice and differences in thickness of
      these layers were identified between WT and Reln(rl/rl) mice. The intensity
      distributions characteristic to the dorsal, middle, and ventral hippocampus were
      altered in the Reln(rl/rl), especially in the ventral hippocampus. These
      differences were quantified using skewness and modeling the intensity
      distributions with a Gaussian mixture. Our results suggest that structural
      features of Reln(rl/rl) brain most closely phenocopy those of patients with
      Norman-Roberts lissencephaly.

PMID- 17185002
TI  - Wavelet-based multi-resolution statistics for optical imaging signals:
      Application to automated detection of odour activated glomeruli in the mouse
      olfactory bulb.
AB  - Optical imaging techniques offer powerful solutions to capture brain networks
      processing in animals, especially when activity is distributed in functionally
      distinct spatial domains. Despite the progress in imaging techniques, the
      standard analysis procedures and statistical assessments for this type of data
      are still limited. In this paper, we perform two in vivo non-invasive optical
      recording techniques in the mouse olfactory bulb, using a genetically expressed
      activity reporter fluorescent protein (synaptopHfluorin) and intrinsic signals of
      the brain. For both imaging techniques, we show that the odour-triggered signals
      can be accurately parameterized using linear models. Fitting the models allows us
      to extract odour specific signals with a reduced level of noise compared to
      standard methods. In addition, the models serve to evaluate statistical
      significance, using a wavelet-based framework that exploits spatial correlation
      at different scales. We propose an extension of this framework to extract
      activation patterns at specific wavelet scales. This method is especially
      interesting to detect the odour inputs that segregate on the olfactory bulb in
      small spherical structures called glomeruli. Interestingly, with proper selection
      of wavelet scales, we can isolate significantly activated glomeruli and thus
      determine the odour map in an automated manner. Comparison against manual
      detection of glomeruli shows the high accuracy of the proposed method. Therefore,
      beyond the advantageous alternative to the existing treatments of optical imaging
      signals in general, our framework propose an interesting procedure to dissect
      brain activation patterns on multiple scales with statistical control.

PMID- 17185003
TI  - Neural correlates of error awareness.
AB  - Error processing results in a number of consequences on multiple levels. The
      posterior frontomedian cortex (pFMC) is involved in performance monitoring and
      signalling the need for adjustments, which can be observed as post-error speed
      accuracy shifts at the behavioural level. Furthermore autonomic reactions to an
      error have been reported. The role of conscious error awareness for this
      processing cascade has received little attention of researchers so far. We
      examined the neural correlates of conscious error perception in a functional
      magnetic resonance imaging (fMRI) study. An antisaccade task known to yield
      sufficient numbers of aware and unaware errors was used. Results from a
      metaanalysis were used to guide a region of interest (ROI) analysis of the fMRI
      data. Consistent with previous reports, error-related activity in the rostral
      cingulate zone (RCZ), the pre-supplementary motor area (pre-SMA) and the insular
      cortex bilaterally was found. Whereas the RCZ activity did not differentiate
      between aware and unaware errors, activity in the left anterior inferior insular
      cortex was stronger for aware as compared to unaware errors. This could be due to
      increased awareness of the autonomic reaction to an error, or the increased
      autonomic reaction itself. Furthermore, post-error adjustments were only observed
      after aware errors and a correlation between post-error slowing and the
      hemodynamic activity in the RCZ was revealed. The data suggest that the RCZ
      activity alone is insufficient to drive error awareness. Its signal appears to be
      useful for post-error speed-accuracy adjustments only when the error is
      consciously perceived.

PMID- 17185004
TI  - Toothed whale monophyly reassessed by SINE insertion analysis: the absence of
      lineage sorting effects suggests a small population of a common ancestral
      species.
AB  - Morphological data have indicated that toothed whales form a monophyletic group.
      However, research published in the last several years has made the issue of the
      monophyly or paraphyly of toothed whales a subject of debate. Our group
      previously characterized three independent loci in which SINE insertions were
      shared among dolphins and sperm whales, thus supporting the traditional,
      morphologically based hypothesis of toothed whale monophyly. Although in recent
      years a few additional molecular works proposed this topology, there is still
      skepticism over this monophyly from the view point of molecular systematics. When
      the phylogeny of rapidly radiated taxa is examined using the SINE method, it is
      important to consider the ascertainment bias that arises when choosing a
      particular taxon for SINE loci screening. To overcome this methodological problem
      specific to the SINE method, we examined all possible topologies among sperm
      whales, dolphins and baleen whales by extensively screening SINE loci from
      species of all three lineages. We characterized nine independent SINE loci from
      the genomes of sperm whales and dolphins, all of which cluster sperm whales and
      dolphins but exclude baleen whales. Furthermore, we characterized ten independent
      loci from baleen whales, all of which were amplified in a common ancestor of
      these whales. From these observations, we conclude that toothed whales form a
      monophyletic group and that no ancestral SINE polymorphisms hinder their
      phylogenetic assignment despite the short divergence times of the major lineages
      of extant whales during evolution. These results suggest that a small population
      of common ancestors of all toothed whales ultimately diverged into the lineages
      of sperm whales and dolphins.

PMID- 17185006
TI  - Patients who develop epilepsy during extended treatment with electroconvulsive
      therapy.
AB  - Epidemiologic data indicate that electroconvulsive therapy (ECT) does not
      precipitate epilepsy. However, when an ECT patient develops this condition, one
      is faced with the question as to whether ECT caused it and whether ECT can be
      safely continued. We describe four patients, two of whom developed definite
      epilepsy and two possible epilepsy during extended courses of ECT. In one of the
      patients ECT was stopped at that point, but in the other three, ECT was continued
      without complications or apparent precipitation of spontaneous seizures. We
      describe some of the clinical challenges in this scenario and provide
      recommendations regarding continued use of ECT in the newly diagnosed epileptic
      patient.

PMID- 17185005
TI  - A phylogenetic and biogeographic perspective on the evolution of poeciliid
      fishes.
AB  - Phylogenetic relationships of members of the subfamily Poeciliinae
      (Cyprinodontiformes) are investigated to test alternate hypotheses of
      diversification resulting from the assembly of the Central America and the
      Caribbean from the Cretaceous period onwards. We use 4333 aligned base pairs of
      mitochondrial DNA and 1549 aligned base pairs of nuclear DNA from 55 samples
      representing 48 ingroup and seven outgroup species to test this hypothesis.
      Mitochondrial genes analyzed include those encoding the 12S and 16S ribosomal
      RNAs; transfer RNAs coding for valine, leucine, isoleucine, glutamine,
      methionine, tryptophan, alanine, asparagine, cysteine and tyrosine; and complete
      cytochrome b and NADH dehydrogenase subunit I and II; nuclear gene analyzed
      included the third exon of the recombination activation gene 1 (RAG1). Analyses
      of combined mtDNA and nuclear DNA data sets result in a well-supported
      phylogenetic hypothesis. This hypothesis is in conflict with the classical
      taxonomic assignment of genera into tribes and phylogenetic hypotheses based on
      the taxonomy; however, the molecular hypothesis defines nine clades that are
      geographically restricted and consistent with the geological evolution of Central
      America and the Caribbean. Our analyses support multiple colonization events of
      Middle America followed by a mix of vicariance and dispersal events.

PMID- 17185007
TI  - High impact running improves learning.
AB  - Regular physical exercise improves cognitive functions and lowers the risk for
      age-related cognitive decline. Since little is known about the nature and the
      timing of the underlying mechanisms, we probed whether exercise also has
      immediate beneficial effects on cognition. Learning performance was assessed
      directly after high impact anaerobic sprints, low impact aerobic running, or a
      period of rest in 27 healthy subjects in a randomized cross-over design.
      Dependent variables comprised learning speed as well as immediate (1 week) and
      long-term (>8 months) overall success in acquiring a novel vocabulary. Peripheral
      levels of brain-derived neurotrophic factor (BDNF) and catecholamines (dopamine,
      epinephrine, norepinephrine) were assessed prior to and after the interventions
      as well as after learning. We found that vocabulary learning was 20 percent
      faster after intense physical exercise as compared to the other two conditions.
      This condition also elicited the strongest increases in BDNF and catecholamine
      levels. More sustained BDNF levels during learning after intense exercise were
      related to better short-term learning success, whereas absolute dopamine and
      epinephrine levels were related to better intermediate (dopamine) and long-term
      (epinephrine) retentions of the novel vocabulary. Thus, BDNF and two of the
      catecholamines seem to be mediators by which physical exercise improves learning.

PMID- 17185009
TI  - Obesity and thrombosis.
AB  - OBJECTIVES: To describe the pathophysiological mechanisms by which obesity
      increases the propensity to thrombosis, the leading cause of death in the Western
      World, with particular emphasis on the role of inflammation, oxidative stress,
      dyslipidaemia, insulin resistance and the coagulation cascade. DESIGN: Review
      article. MATERIALS AND METHODS: Medline (1966-2005) and Cochrane library review
      of literature examining the relationship between obesity and thrombosis. Search
      terms included obesity, overweight, body mass index, thrombosis, cardiovascular
      disease, venous thromboembolism, peripheral arterial disease, and coronary heart
      disease. RESULTS: Obesity is an important and growing public health issue that is
      estimated to affect more than half of the UK adult population. Obesity, in
      particular central (visceral) obesity, is associated with significant, and
      largely preventable, morbidity and mortality including an increased incidence and
      prevalence of arterial and venous thrombotic events. The various mechanisms by
      which obesity may cause thrombosis include: the actions of so-called
      adipocytokines from adipose tissue, e.g. leptin and adiponectin; increased
      activity of the coagulation cascade and decreased activity of the fibrinolytic
      cascade; increased inflammation; increased oxidative stress and endothelial
      dysfunction; and disturbances of lipids and glucose tolerance in association with
      the metabolic syndrome. CONCLUSIONS: Obesity appears to be associated with
      thrombosis via several mechanisms. These pro-thrombotic factors are all improved
      by weight loss.

PMID- 17185008
TI  - Associative and spatial learning and memory deficits in transgenic mice
      overexpressing the RNA-binding protein HuD.
AB  - HuD is a neuronal specific RNA-binding protein associated with the stabilization
      of short-lived mRNAs during brain development, nerve regeneration and synaptic
      plasticity. To investigate the functional significance of this protein in the
      mature brain, we generated transgenic mice overexpressing HuD in forebrain
      neurons under the control of the alphaCaMKinII promoter. We have previously shown
      that one of the targets of HuD, GAP-43 mRNA, was stabilized in neurons in the
      hippocampus, amygdala and cortex of transgenic mice. Animals from two independent
      lines expressing different levels of the transgene were subjected to a battery of
      behavioral tests including contextual fear conditioning and the Morris water
      maze. Our results show that although HuD is increased after learning and memory,
      constitutive HuD overexpression impaired the acquisition and retention of both
      cued and contextual fear and the ability to remember the position of a hidden
      platform in the Morris water maze. No motor-sensory abnormalities were observed
      in HuD transgenic mice, suggesting that the poor performance of the mice in these
      tests reflect a true cognitive impairment. We conclude that posttranscriptional
      regulation of gene expression by stabilization of specific mRNAs may have to be
      restricted temporally and spatially for proper acquisition and storage of
      memories.

PMID- 17185010
TI  - The rationale for using HMG-CoA reductase inhibitors ('statins') in peripheral
      arterial disease.
AB  - Atherosclerosis is a systemic process, and the leading cause of morbidity and
      mortality in the developed world. HMG-CoA reductase inhibitors ('statins') are
      potent lipid lowering drugs, which have been shown to reduce morbidity and
      mortality in patients with coronary atherosclerosis. OBJECTIVE: To present the up
      to-date data concerning statin use in the prevention and treatment of extra
      coronary atherosclerosis. METHODS: Clinical trials with statins in patients with
      extra-coronary atherosclerosis were searched for via PUBMED. FINDINGS AND
      CONCLUSIONS: The different forms of peripheral arterial disease (e.g.
      cerberovascular disease, lower extremity peripheral arterial disease) are
      associated with significant cardiovascular morbidity and mortality, and hence
      constitute a coronary artery disease equivalent in terms of published practice
      guidelines. There is some evidence from small randomized controlled trials that
      statin therapy decreases cardiovascular morbidity and mortality in patients with
      peripheral arterial disease. The mechanism of action of statins may derive from
      their lipid lowering properties, or from other, pleiotropic effects. Further,
      larger randomized controlled studies with statins are needed to evaluate the
      efficacy of statin therapy in patients with stable peripheral arterial disease
      and in those undergoing vascular or endovascular surgery.

PMID- 17185012
TI  - Modulation of temperature-sensitive TRP channels.
AB  - Animals sense temperature--either cold or hot--by the direct activation of
      temperature-sensitive members of the TRP family of ion channels, the thermo-TRPs.
      To date, six TRP channels--TRPV1-4, TRPM8 and TRPA1--have been reported to be
      directly activated by heat and to be involved in thermosensation. Temperature
      sensing can be modulated by phosphorylation of intracellular residues by protein
      kinases or by insertion of new channels into the cell membrane. In this review we
      provide a brief overview of the properties of thermo-TRPs, and we summarise
      signalling pathways involved in their regulation.

PMID- 17185011
TI  - Mouse bone marrow and peripheral blood erythroid cell counts are regulated by
      different autosomal genetic loci.
AB  - Erythropoiesis is under fine control and genetic loci that affect it are likely
      to be important in a range of conditions. To assess the relative contributions of
      different genetic loci to parameters of erythropoiesis, we have measured RBC
      counts in the peripheral circulation and committed erythroid cells (RBC and small
      normoblasts) in the bone marrow in a cohort of (CBA/H x C57BL/6) F2 mice to map
      quantitative trait loci (QTL). Candidate genes were assessed using bioinformatics
      and DNA sequencing. Different autosomal loci affect bone marrow (chromosomes 5,
      11 and 19) and peripheral blood (chromosome 4) erythroid cell counts but there
      may be a common chromosome X locus. Spleen weight QTL were found on chromosomes
      3, 15 and 17. Surprisingly, erythropoietin (Epo) is the best candidate
      quantitative trait gene (QTG) in the chromosome 5 locus that affects bone marrow
      but not peripheral blood erythroid cell counts. Epo gene expression is known to
      be genetically regulated in mice, but our data suggest a tissue-specific role for
      epo in mouse erythropoiesis that is also genetically determined. The identity of
      the other QTG will be important both to further knowledge of the control of
      erythropoiesis and as potential modifier genes for haematological disorders.

PMID- 17185014
TI  - The development of oral lesions in lambs naturally infected with orf virus.
AB  - Stomatitis in sheep caused by orf virus can be confused with lesions of more
      economically significant diseases, including foot-and-mouth disease, but there is
      no published account of the sequential development of oral orf lesions in the
      sheep. This report describes the clinical appearance of such lesions during a
      natural outbreak of the disease in young lambs. Lesions were seen on the gingiva,
      the tongue and the dental pad/hard palate, and progressed from small erythematous
      papules to larger, often coalescing papules that in some cases were ulcerated.
      Resolution started within seven days and was complete within 22 days. The lambs
      continued to suck and thrive throughout the infection. Lesions at all stages were
      proliferative, providing a major differentiating factor between orf and other
      causes of stomatitis in sheep.

PMID- 17185015
TI  - False diagnosis of papilloedema and idiopathic intracranial hypertension.
AB  - The diagnosis of idiopathic intracranial hypertension (IIH) relies heavily on the
      appearance of the optic disc. We report eighteen children referred to us over a 3
      year period with disc swelling and suspected IIH. Following a tertiary
      ophthalmological review, papilloedema was excluded in ten with buried drusen,
      disc crowding, pseudopapilloedema, or misinterpretation of normal appearances. In
      these ten children, five had a mean opening pressure on lumbar puncture of 27.2
      cm H2O, range 19-32, which was significantly lower than those with IIH (37.5 cm
      H2O, range 29-47; p<0.01). We conclude that diagnosis of IIH is difficult, and
      that more precisely defined criteria for assessment and diagnosis are needed.

PMID- 17185016
TI  - Intravenous ketoprofen as an adjunct to patient-controlled analgesia morphine in
      adolescents with thoracic surgery: a placebo controlled double-blinded study.
AB  - BACKGROUND: Surgery to correct pectus deformities entail substantial destruction
      of the thoracic skeleton and thus may cause significant postoperative pain. AIMS:
      To evaluate the efficacy of intravenous ketoprofen, a NSAID, as an adjunct to PCA
      morphine in pain treatment in children having pectus surgery. METHODS: Thirty-one
      children aged 10-15 years completed the study according to protocol. Children
      (n=14) in the ketoprofen-group received ketoprofen 1mg/kg i.v. at the skin
      closure, and at 8 and 16 h after surgery, while children (n=17) in the placebo
      group received normal saline, respectively. For rescue analgesia the patient had
      an access to PCA-morphine. The children expressed their pain by a coloured VAS.
      RESULTS: Mean cumulative 24h morphine dose used was less in the ketoprofen-group
      (mean+/-SD: 490+/-240 microg/kg) than in the placebo-group (670+/-200 microg/kg)
      (mean difference 180 microg/kg, 95% CI for diff: 15-340 microg/kg, P=0.03). The
      area under the pain intensity-time-curve was lower in the ketorpofen-group (49+/
      26 score hour) than in the placebo-group (68+/-24 score hour) (mean difference 21
      score hour, 95% CI for diff: 3-40 score hour, P=0.026). There was no difference
      between the two groups in adverse events, 4/14 in the ketoprofen group and 8/17
      in the placebo-group developed oxygen desaturation, and one patient in the
      ketoprofen-group developed bleeding at 5h after surgery. CONCLUSIONS: Intravenous
      ketoprofen in adjunct to PCA morphine provided a significant opioid sparing
      effect and improved analgesia in children having chest wall correction surgery.

PMID- 17185017
TI  - Physical, biochemical and functional characterization of haemoglobin from three
      strains of Artemia.
AB  - The brine shrimp, Artemia, an inhabitant of coastal and inland salterns,
      encounter fluctuations in the salinity which in turn influences the oxygen
      availability of their habitat. Hence, experiments were performed to analyze
      variations in haemoglobin structure and patterns of three strains of Artemia from
      South India and also to reflect the effect of varying oxygen levels in their
      habitat. Haemoglobins were purified on a DEAE-Sephadex column and haemoglobin
      types were analyzed by comparing their relative mobility on a non-denaturing
      medium. Furthermore, their molecular masses were determined by gel filtration in
      Sepharose column and by dodecylsulfate polyacrylamide gel electrophoresis.
      Results clearly reveal the presence of three distinct extracellular haemoglobins
      Hb I, Hb II and Hb III in Tuticorin strain while the other strains displayed only
      trails or the complete absence of Hb III and Hb II. Estimated molecular masses of
      these haemoglobins are 235,000-250,000 Da. Denaturation of the reduced and
      alkylated haemoglobins revealed apparently one polypeptide chain with a molecular
      mass of 124,000 Da. Upon denaturing gel electrophoresis of native haemoglobin Hb
      II, it was found that the 124,000 Da, polypeptide was cleaved specifically into
      two unequally-sized fragments of 50,400 and 79,800 Da. With regard to oxygen
      affinity, Hb III has a very high affinity for oxygen, an almost negligible Bohr
      effect and a good physiological adaptation to temperature changes. By combining
      the three haemoglobins in different proportions Artemia strains must be able to
      withstand diverging environmental conditions. In particular, the absence of Hb
      III in Puthalam and its occurrence as a faint band in Thamaraikulam could be
      correlated to the oxygen levels of their habitats.

PMID- 17185019
TI  - Mutations causing biotinidase deficiency in children ascertained by newborn
      screening in Western Hungary.
AB  - In Hungary the national newborn screening programme for the detection of
      biotinidase deficiency was launched in 1989. In this study, we determined the
      genotypes of all patients identified at the Budapest Screening Centre that covers
      half of the country. The incidence of the disorder in Western Hungary is about
      three times the worldwide incidence. Overall, 21 different mutations were
      identified in 49 patients, including four novel mutations. Ten mutations proved
      to be unique to the Hungarian population.

PMID- 17185018
TI  - Lysosomal accumulation of SCMAS (subunit c of mitochondrial ATP synthase) in
      neurons of the mouse model of mucopolysaccharidosis III B.
AB  - The neurodegenerative disease MPS III B (Sanfilippo syndrome type B) is caused by
      mutations in the gene encoding the lysosomal enzyme alpha-N
      acetylglucosaminidase, with a resulting block in heparan sulfate degradation. A
      mouse model with disruption of the Naglu gene allows detailed study of brain
      pathology. In contrast to somatic cells, which accumulate primarily heparan
      sulfate, neurons accumulate a number of apparently unrelated metabolites,
      including subunit c of mitochondrial ATP synthase (SCMAS). SCMAS accumulated from
      1 month of age, primarily in the medial entorhinal cortex and layer V of the
      somatosensory cortex. Its accumulation was not due to the absence of specific
      proteases. Light microscopy of brain sections of 6-months-old mice showed SCMAS
      to accumulate in the same areas as glycosaminoglycan and unesterified
      cholesterol, in the same cells as ubiquitin and GM3 ganglioside, and in the same
      organelles as Lamp 1 and Lamp 2. Cryo-immuno electron microscopy showed SCMAS to
      be present in Lamp positive vesicles bounded by a single membrane (lysosomes), in
      fingerprint-like layered arrays. GM3 ganglioside was found in the same lysosomes,
      but was not associated with the SCMAS arrays. GM3 ganglioside was also seen in
      lysosomes of microglia, suggesting phagocytosis of neuronal membranes. Samples
      used for cryo-EM and further processed by standard EM procedures (osmium
      tetroxide fixation and plastic embedding) showed the disappearance of the SCMAS
      fingerprint arrays and appearance in the same location of "zebra bodies", well
      known but little understood inclusions in the brain of patients with
      mucopolysaccharidoses.

PMID- 17185020
TI  - A phase I/II clinical trial of enzyme replacement therapy in
      mucopolysaccharidosis II (Hunter syndrome).
AB  - OBJECTIVE: To evaluate the safety and explore the efficacy of idursulfase
      (recombinant human iduronate-2-sulfatase) treatment for mucopolysaccharidosis II
      (MPS II). STUDY DESIGN: Twelve patients were enrolled into a randomized, double
      blind, placebo-controlled trial for 24 weeks followed by an open-label extension
      study. Three groups of 4 patients were enrolled sequentially, with 3 patients in
      each group receiving idursulfase and 1 patient receiving placebo. The first group
      received idursulfase at 0.15 mg/kg infused every other week with the 2nd and 3rd
      groups receiving 0.5 and 1.5 mg/kg, respectively. After 24 weeks the placebo
      treated patients were changed to idursulfase at the dose of their group. The
      primary endpoint was a change from baseline in urinary excretion of
      glycosaminoglycans. Results were pooled for analysis by ANOVA and compared to
      baseline. RESULTS: Urinary glycosaminoglycans were reduced within 2 weeks of
      initiating idursulfase and were decreased 49% after 48 weeks of treatment
      (P<0.0001). Both liver and spleen volume were decreased at 24 weeks (P<0.01) and
      48 weeks (P<0.001). The 6-minute walk test distance increased an average of 48
      meters after 48 weeks (P=0.013). Six patients in the higher dose groups developed
      IgG antibodies that did not influence the clinical effects of idursulfase.
      CONCLUSIONS: This study describes the first experience with enzyme replacement
      therapy for the treatment of patients with MPS II. Idursulfase was generally well
      tolerated and was associated with reductions in urine glycosaminoglycans levels
      and organ size, as well as an increased 6-minute walk test distance.

PMID- 17185021
TI  - Electrodeposition of polythiophene assisted by sonochemistry and incorporation of
      fluorophores in the polymeric matrix.
AB  - This work studies the effect of an ultrasonic field of 530 kHz frequency on the
      electrodeposition of polythiophene in an acetonitrile solution using lithium
      perchlorate as background electrolyte. The results obtained show an increase in
      the polymer mass transfer produced and a more compact and homogenous morphology
      of the films yielded by sonoelectrochemistry. Electrodeposition of the polymer
      was also carried out in the presence of the fluorophores Harmane (1-methyl-9H
      pyrido[3,4-b]indole) or BCCM (9H-pyrido[3,4-b]indole-3-carboxylic acid methyl
      ester). Confocal microscopy measurements performed on the films synthesised in
      the presence of these compounds showed that the latter are embedded in the
      polymer when it is sonoelectrogenerated at a potential of 2.2, 2.5 or 2.8 V.
      Films generated in the absence of ultrasound showed no fluorescence.

PMID- 17185022
TI  - Ocular extracellular matrices in development.
AB  - The extracellular matrix is known to play important roles in regulating tissue
      development and cell differentiation. At a basic level the matrix is the
      substratum to which cells adhere and over which they migrate during
      morphogenesis. The recognition and adhesion of cells to matrices, especially to
      specialized matrices such as basal laminae, in developing tissues plays an
      important role in their decision to adhere or move on, to continue mitosis, to
      differentiate or to undergo apoptosis. The matrix is also the milieu from which
      growth factors and morphogens interact with the cell. Recent work demonstrates
      that matrix molecules are often active participants in these signaling processes,
      regulating the cellular response. Our understanding of the complexity of
      different ocular matrices continues to grow with the characterization of new
      proteins that modify collagen fibrils or serve as ligands for cell surface
      adhesion receptors. This review looks at those aspects of development in major
      tissues of the vertebrate eye where the extracellular matrix is known to
      participate, or is likely to do so based on similar roles in the development of
      the embryonic forebrain or other tissues. It concludes by highlighting some of
      the major developmental questions about the roles of the matrix in development in
      several ocular tissues.

PMID- 17185024
TI  - MALDI-MS-based imaging of small molecules and proteins in tissues.
AB  - The direct analysis of tissues using matrix-assisted laser desorption/ionization
      mass spectrometry (MALDI-MS) enables both endogenous and exogenous compounds
      present in tissues to be detected with molecular specificity while maintaining
      their spatial orientation. This unique combination, coupled with excellent
      sensitivity and rapid analysis time, presents many potential advantages to a wide
      range of applications in diverse biological fields. Recent advances have shown
      how the technique can be applied to cancer research, neuroscience and
      pharmaceutical development. Examples include the use of unique protein profiles
      to classify human tumor tissues and predict patient outcomes, the discovery of
      protein changes in mouse cerebellum as a function of development, and the two
      dimensional visualization of the distribution of a drug and first-pass
      metabolites in rat whole-body sections.

PMID- 17185023
TI  - Amyloid-beta peptide affects the oxygen dependence of erythrocyte metabolism: a
      role for caspase 3.
AB  - Human erythrocyte metabolism is modulated by the cell oxygenation state. Among
      other mechanisms, competition of deoxyhemoglobin and some glycolytic enzymes for
      the cytoplasmic domain of band 3 is probably involved in modulation. This
      metabolic modulation is connected to variations in intracellular NADPH and ATP
      levels as a function of the oxygenation state of the cell, and, consequently, it
      should have physiologic relevance. The present study investigates the effect of
      amyloid-beta peptide exposure on this metabolic modulation and its relationship
      with the activity of erythrocyte caspase 3. Metabolic differences between
      erythrocytes incubated at high and low oxygen saturation disappear following to
      24 h exposure to amyloid-beta peptide. Western blotting analysis shows that
      caspase 3 is concurrently activated. Pre-incubation of amyloid-beta peptide
      treated erythrocytes with a specific inhibitor of caspase 3, partially restores
      the oxygen-dependent modulation. This finding suggests that human erythrocytes
      following to exposure to amyloid-beta peptide show a complete loss of the oxygen
      dependent metabolic modulation, which is partially restored by caspase 3
      inhibitor-treatment.

PMID- 17185025
TI  - Spatial distribution of methane over Lake Baikal surface.
AB  - The results of application of a high sensitivity methane laser detector to
      investigations of the methane concentration in the atmosphere over Baikal lake
      are presented as well as methane flows from the water into the atmosphere. The
      measurements were conducted at a stationary station and aboard the research
      vessel "Vereschagin" during two summer expeditions in 2003 and 2004. Mean
      background concentration was equal to (2.00+/-0.16) ppm in August 2003 and
      (1.90+/-0.07) ppm in June 2004. The areas of methane emission through the water's
      surface are found to be distinctly localized and to have a characteristic size of
      about 150-300 m in diameter. The methane concentration in the centers of these
      areas can reach approximately 27 ppm. Methane flows into the atmosphere in some
      Baikal regions were measured as well.

PMID- 17185026
TI  - Two-channel opto-acoustic diode laser spectrometer and fine structure of methane
      absorption spectra in 6070-6180 cm-1 region.
AB  - We describe the hardware and software of the high-sensitive two-channel opto
      acoustic spectrometer with a near infrared diode laser. A semiconductor TEC-100
      laser with outer resonator generates a continuous single-frequency radiation in
      the range of 6040-6300 cm-1 with spectral resolution better that 10 MHz. The
      newly designed model of photo-acoustic cells in the form of a ring type resonator
      was used in the spectrometer, and the system allows the measurement of a weak
      absorption coefficient equal to 1.4x10(-7) cm-1 Hz-1/2 with a laser radiation
      power of 0.003 W. The methane absorption spectra within a range of 6080-6180 cm-1
      were measured with a spectral resolution of 10 MHz and the signal to noise ratio
      more than 10(3). Six hundred absorption lines were recorded, which is twice as
      many as in HITRAN-2004. The accurate measurements of the half-width and shift of
      methane unresolved triplet R3 of 2nu3 band permit us to determine values of the
      broadening and shift coefficients for CH4-air, CH4-N2, and CH4-SF6 mixtures.

PMID- 17185027
TI  - Pressure-induced shift and broadening of acetylene lines in the region 6580-6600
      cm-1.
AB  - Highly accurate measurements of pressure shift and broadening parameters of
      acetylene absorption lines in the region 6580-6600 cm-1 have been performed by
      tunable diode laser spectroscopy (TDLS). For these purposes the three channel
      spectrometer with distributed-feedback diode laser, operated at 1.53 microm was
      used. The laser is generating pulses of 4-10 ms duration at a repetition
      frequency of 40 Hz. A temperature-stabilization system, using a thermoelectric
      cooling unit affords a temperature stability of the order of 10(-4)K in the
      temperature range from -15 to +50 degrees C. A three channels acquisition system
      ensured simultaneous real time recording of the sample gas absorption spectrum
      and of two spectral calibration signals (Fabry-Perot fringes and low-pressure
      reference lines). We have measured the pressure-induced self-shift and broadening
      coefficients for six lines of the R-branch in the nu1+nu3 rotation-vibration band
      of acetylene 12C2H2. The self-shift coefficients have been determined for these
      lines in the wide pressure region. A non-linear behavior of the pressure
      dependence of the shift was observed. The temperature exponent n of pressure
      induced broadening and shift are reported.

PMID- 17185028
TI  - Spectroscopic and theoretical studies on cobalt (II) complex of
      maleonitriledithiolate and 5-nitro-1,10-phenanthroline.
AB  - The molecular structure, electronic and infrared spectroscopic properties of the
      title complex Co(mnt)(5-NO(2)-phen) (mnt(2-) = maleonitriledithiolate, 5-NO(2)
      phen = 5-nitro-1,10-phenanthroline) were studied in this paper. With non
      empirical density functional theory (DFT) methods, the gaseous molecular geometry
      of the complex was optimized and corresponding vibrational spectra was obtained.
      A complete assignment to the IR spectra of such a complicated molecule has been
      exhibited. And the established scientific method could give a complete and
      accurate analysis about the vibrational spectra of this complex. An electronic
      spectra was calculated by ZINDOS/S method. The results showed that the calculated
      values agreed with the observed ones.

PMID- 17185029
TI  - Crystal growth and vibrational spectroscopic studies of the semiorganic non
      linear optical crystal--bisthiourea magnesium sulphate.
AB  - The semiorganic non-linear optical crystal bisthiourea magnesium sulphate (BTMS)
      was grown by slow evaporation technique using water as solvent. Vibrational
      spectra were recorded to determine the symmetries of molecular vibrations. The
      observed Raman and infrared bands were also assigned and discussed. The optical
      transmission spectral study was carried out to test the transmitting ability of
      the crystal in the visible range. The second harmonic generation test of BTMS
      revealed the non-linear nature of the crystal. The TGA/DTA curve was also
      recorded for the experimental crystal.

PMID- 17185030
TI  - Reliability of diagnoses coding with ICD-10.
AB  - OBJECTIVE: Reliability of diagnoses coding is essential for the use of routine
      data in a national health care system. The present investigation compares
      reliability of diagnoses coding with ICD-10 between three groups of coding
      subjects. METHOD: One hundred and eighteen students coded 15 diagnoses lists, 27
      medical managers from hospitals 34 discharge letters, and 13 coding specialists
      12 discharge letters. Agreement in principal diagnosis was assessed using Cohen's
      Kappa and the fraction of coincidences over the number of pairs, agreement for
      the full set of diagnoses with a previously developed measure p(om). RESULTS:
      Kappa values were fair (managers) or moderate (coders) for terminal codes with
      0.27 and 0.42 (agreement 29.2% versus 46.8%), substantial for the chapter level
      with 0.71 and 0.72 (agreement 78.3% versus 80.8%). p(om) was lower for the full
      set of diagnoses than for principal diagnoses, for example in case of managers
      with 0.21 versus 0.29 for terminal codes. Best results were achieved by students
      coding diagnoses lists. In summary, the results are remarkably lower than in
      earlier publications. CONCLUSION: The refinement of the ICD-10 accompanied by
      innumerous coding rules has established a complex environment that leads to
      significant uncertainties even for experts. Use of coded data for quality
      management, health care financing, and health care policy requires a remarkable
      simplification of ICD-10 to receive a valid image of health care reality.

PMID- 17185031
TI  - Evaluation of the Abbott RealTime HCV assay for quantitative detection of
      hepatitis C virus RNA.
AB  - BACKGROUND: The Abbott RealTime HCV assay for quantitative detection of HCV RNA
      has recently been introduced. OBJECTIVES: In this study, the performance of the
      Abbott RealTime HCV assay was evaluated and compared to the COBAS AmpliPrep/COBAS
      TaqMan HCV test. STUDY DESIGN: Accuracy, linearity, interassay and intra-assay
      variations were determined, and a total of 243 routine clinical samples were
      investigated. RESULTS: When accuracy of the new assay was tested, the majority of
      results were found to be within +/-0.5 log(10) unit of the results obtained by
      reference laboratories. Determination of linearity resulted in a quasilinear
      curve up to 1.0 x 10(6)IU/ml. The interassay variation ranged from 15% to 32%,
      and the intra-assay variation ranged from 5% to 8%. When clinical samples were
      tested by the Abbott RealTime HCV assay and the results were compared with those
      obtained by the COBAS AmpliPrep/COBAS TaqMan HCV test, the results for 93% of all
      samples with positive results by both tests were found to be within +/-1.0
      log(10) unit. The viral loads for all patients measured by the Abbott and Roche
      assays showed a high correlation (R(2)=0.93); quantitative results obtained by
      the Abbott assay were found to be lower than those obtained by the Roche assay.
      CONCLUSIONS: The Abbott RealTime HCV assay proved to be suitable for use in the
      routine diagnostic laboratory. The time to results was similar for both of the
      assays.

PMID- 17185032
TI  - Plasma cholesteryl ester transfer protein mass and phospholipid transfer protein
      activity are associated with leptin in type 2 diabetes mellitus.
AB  - Adipose tissue contributes to plasma levels of lipid transfer proteins and is
      also the major source of plasma adipokines. We hypothesized that plasma
      cholesteryl ester transfer protein (CETP) mass, phospholipid transfer protein
      (PLTP) activity and cholesteryl ester transfer (CET, a measure of CETP action)
      are determined by adipokine levels. In this study, relationships of plasma CETP
      mass, PLTP activity and CET with leptin, resistin and adiponectin were analyzed
      in type 2 diabetic patients and control subjects. Plasma PLTP activity (P<0.001),
      CET (P<0.001), leptin (P=0.003), resistin (P<0.001), high sensitive C-reactive
      protein (P=0.005), and insulin resistance (HOMA(ir)) (P<0.001) were higher,
      whereas HDL cholesterol (P<0.001) and plasma adiponectin (P<0.001) were lower in
      83 type 2 diabetic patients (32 females) than in 83 sex-matched control subjects.
      Multiple linear regression analysis demonstrated that in diabetic patients plasma
      leptin levels were related to plasma CETP mass (P=0.018) and PLTP activity
      (P<0.001), but not to the other adipokines measured. Plasma CET was inversely
      correlated with adiponectin in univariate analysis, but this association
      disappeared in multivariate models that included plasma lipids and CETP. In
      conclusion, both plasma CETP mass and PLTP activity are associated with plasma
      leptin in type 2 diabetes. The elevated CET in these patients is not
      independently related to any of the measured plasma adipokines.

PMID- 17185033
TI  - Spectral entropy assessment with auditory evoked potential in neuroanesthesia.
AB  - OBJECTIVE: The assessment of the level of anesthesia is a very hard task, since
      no gold standard has stood out in the past three decades. Middle Latency Auditory
      Evoked Potential (MLAEP) is one of the most popular neurophysiological tools for
      anesthesia monitoring. Recently, Spectral Entropy (SpEn) has been introduced: it
      provides two different parameters, State Entropy (SE) and Response Entropy (RE).
      The aim of this prospective study is to check SpEn end-point, comparing it to
      MLAEPs in neurosurgical anesthesia. METHODS: Twenty patients submitted to
      elective supratentorial neurosurgery for removal of a temporal-parietal
      meningioma were included in the study. SpEn and MLAEPs were simultaneously
      monitored using the M-entropy module S/5 (GE Health Care, Helsinki, Finland) and
      Alaris Medical System AEP-ARX index monitor (AAI) (Kidemosevej, Denmark),
      respectively. RESULTS: Four thousand and sixty four data points of SE, RE and AAI
      were recorded and ROC curves comparing AAI to RE and SE showed a highly
      significant (p<0.0001) area under the curve. The RE and SE cut-off values
      (showing maximal sensitivity with maximal specificity) to discriminate anesthesia
      from awake or consciousness sedation were 61 and 58, respectively. However, in a
      group of data points, low AAI was associated to high SpEn (577 data points for RE
      and 770 for SE) and vice versa (31 data points for RE and 43 for SE). The
      prediction probability for SE was 0.977 and for RE was 0.968. CONCLUSIONS: Our
      results suggest that SpEn is as effective as AAI. SIGNIFICANCE: Our results show
      that SpEn is able to discriminate between the levels of wakefulness and surgical
      anesthesia. However, the meaning of data showing a discrepancy between AAI and
      SpEn is not yet clear and calls for further study.

PMID- 17185034
TI  - Morphological events during the Trypanosoma cruzi cell cycle.
AB  - The replication and segregation of organelles producing two identical daughter
      cells must be precisely controlled during the cell cycle progression of
      eukaryotes. In kinetoplastid flagellated protozoa, this includes the duplication
      of the single mitochondrion containing a network of DNA, known as the
      kinetoplast, and a flagellum that grows from a cytoplasmic basal body through the
      flagellar pocket compartment before emerging from the cell. Here, we show the
      morphological events and the timing of these events during the cell cycle of the
      epimastigote form of Trypanosoma cruzi, the protozoan parasite that causes
      Chagas' disease. DNA staining, flagellum labeling, bromodeoxyuridine
      incorporation, and ultra-thin serial sections show that nuclear replication takes
      10% of the whole cell cycle time. In the middle of the G2 stage, the new
      flagellum emerges from the flagellar pocket and grows unattached to the cell
      body. While the new flagellum is still short, the kinetoplast segregates and
      mitosis occurs. The new flagellum reaches its final size during cytokinesis when
      a new cell body is formed. These precisely coordinated cell cycle events conserve
      the epimastigote morphology with a single nucleus, a single kinetoplast, and a
      single flagellum status of the interphasic cell.

PMID- 17185035
TI  - Daily intake of di(2-ethylhexyl)phthalate (DEHP) by German children -- A
      comparison of two estimation models based on urinary DEHP metabolite levels.
AB  - Di(2-ethylhexyl)phthalate (DEHP) is a general-purpose plasticizer for polyvinyl
      chloride (PVC) and has become a ubiquitous environmental contaminant. It is
      suspected to be an endocrine disrupting/modulating substance in humans. Children
      are of special concern due to their developmental state. In our study we
      estimated the daily DEHP intake of 239 children aged 2-14 years by extrapolating
      from their urinary levels of the DEHP metabolites mono-(2-ethyl-5
      hydroxyhexyl)phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP)
      and mono-(2-ethylhexyl)phthalate (MEHP). We applied two calculation models based
      upon the volume and the creatinine-related urinary metabolite concentrations.
      Applying the volume- or the creatinine-based calculation model we determined a
      median daily DEHP intake of 7.8 or 4.3 microg/kgbody weight (bw)/day and a 95th
      percentile of 25.2 or 15.2 microg/kgbw/day. Three children (1%) exceeded the
      value of the tolerable daily intake (TDI) of the European Food Safety Authority
      of 50 microg/kgbw/day, while 7.5% or 3% (depending on the calculation model)
      exceeded the reference dose (RfD) of 20 microg/kgbw/day of the US Environmental
      Protection Agency. In general, DEHP exposure was decreasing with increasing age
      and boys had higher exposures than girls. Our findings suggest that the majority
      of the children in the general population is exposed to quantities of DEHP below
      the TDI and the RfD. However, many children scoop out the preventive limit values
      to a considerable degree and in individual cases we observed substantial
      transgressions. Younger children seem to be more severely burdened, which may be
      due to a higher food consumption related to their bw, mouthing behaviour and/or
      playing near the ground.

PMID- 17185036
TI  - A supportive nursing care clinic: conceptions of patients with head and neck
      cancer.
AB  - Patients with head and neck cancer have complex long-lasting physical and
      psychosocial needs due to illness and treatment, and studies have shown
      deficiencies concerning support in these respects. The purpose of this study was
      to describe how head and neck cancer patients with eating problems conceived the
      significance of a supportive nursing care clinic before, during and after
      completion of radiotherapy. Thematic interviews were carried out in an open
      dialogue with 12 patients treated with radiotherapy for head and neck cancer. The
      phenomenologischer method was used in the analyses. The findings showed that the
      nurse clinic could meet head and neck cancer patients' needs of safety and
      security, which was especially important before and after completion of treatment
      when no other regular contacts in the health care system existed. The
      significance of the nurse clinic varied depending on where in the trajectory the
      patients were, what needs and problems they experienced, and how severe these
      were experienced by the individual patient. The supportive nursing care clinic
      could meet these patients' needs of knowledge, care and support both concerning
      practical measures related to the disease and its treatment, and emotional needs.
      This way of organising the care can contribute to these patients' health and
      wellbeing.

PMID- 17185037
TI  - Innate resistance to Entamoeba histolytica in murine models.
AB  - Hamano et al. have recently reported that in murine models of amebiasis, innate
      resistance is associated with nonhemopoietic cells and depends on the activity of
      interleukin-10. This article raises the issue of the importance of predisposition
      to amebic colitis and discusses which host factors have a role in innate
      resistance to invasive disease. Resistance studies that elucidate the mechanisms
      involved in parasite clearance or parasite invasion are essential to
      understanding the incidence of amebiasis in humans.

PMID- 17185038
TI  - Cholesterol: a potential therapeutic target in Leishmania infection?
AB  - Leishmania are obligate intracellular parasites that invade and survive within
      host macrophages and can result in visceral leishmaniasis, a major public health
      problem worldwide. The entry of intracellular parasites, in general, involves
      interaction with the plasma membrane of host cells. Cholesterol in host cell
      membranes was recently shown to be necessary for binding and internalization of
      Leishmania and for the efficient presentation of leishmanial antigens in infected
      macrophages. This article describes the need to explore cyclodextrin-based
      compounds, which modulate host membrane cholesterol levels, as a possible
      therapeutic strategy against leishmaniasis in addition to other intracellular
      parasites.

PMID- 17185039
TI  - Neospora caninum emerges from the shadow of Toxoplasma gondii.
AB  - It is sometimes easy to make the mistake of assuming that everything that holds
      true for Toxoplasma gondii is also true for its relative Neospora caninum.
      However, a recurring theme in the recent review by Hemphill et al. is not the
      similarities but the striking differences between the two parasites.

PMID- 17185040
TI  - CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells:
      potential role for CB2-selective ligands as immunosuppressive agents.
AB  - Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the
      nervous and immune system, respectively, and mediate a wide range of effects,
      including anti-inflammatory properties. However, cannabinoids that bind CB1 are
      also psychoactive thereby limiting their clinical use. In this study, we
      investigated the immunosuppressive properties of JWH-015, a synthetic CB2
      selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in
      vitro and inhibited the proliferative response of T and B cells to mitogens
      through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and
      intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as
      well as loss of mitochondrial membrane potential. Finally, administration of JWH
      015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell
      response to mitogens. Together, this study suggests that CB2-selective agonists,
      devoid of psychotropic effect, may serve as novel anti
      inflammatory/immunosuppressive agents.

PMID- 17185041
TI  - Transient regulatory T-cells: a state attained by all activated human T-cells.
AB  - CD4(+)CD25(+)FOXP3(+) regulatory T-cells (T(regs)) form an important arm of the
      immune system responsible for suppressing untoward immune responses. T(regs) can
      be thymically derived or peripherally induced, even from CD4(+)CD25(-)FOXP3(-) T
      cells. FOXP3 expression and in vitro suppressive activity are considered unique
      hallmarks of this dedicated and stable lineage of regulatory cells. Here we show
      that virtually all human CD4(+)CD25(-)FOXP3(-) T-cells and CD8(+)CD25(-)FOXP3(-)
      T-cells attain a transient FOXP3(+)CD25(+) state during activation. In this state
      of activation, these cells possess the classic phenotype of T(regs), in that they
      express similar markers and inhibit in vitro proliferation of autologous
      CD4(+)CD25(-) T-cells. This state is characterized by suppressed IFN-gamma
      production and robust TNF-alpha and IL-10 production. Interestingly, the great
      majority of the activated cells eventually downregulate FOXP3 expression, with a
      concomitant drop in suppressive ability. Our results show that, in humans, FOXP3
      expression and T(reg) functionality are not exclusive features of a stable or
      unique lineage of T-cells but may also be a transient state attained by almost
      all T-cells. These results warrant caution in interpreting human studies using
      FOXP3 and suppressive activity as readouts and suggest that attempts to induce
      "T(regs)" may paradoxically result in induction of effector T-cells, unless
      stability is confirmed.

PMID- 17185042
TI  - Surveillance of methadone-related adverse drug events using multiple public
      health data sources.
AB  - Healthcare safety and quality surveillance is increasingly conducted by public
      health agencies. We describe a biomedical informatics method that uses multiple
      public health data sources to perform surveillance of methadone-related adverse
      drug events. Data from Utah medical examiner records, vital statistics, emergency
      department encounter administrative data and a database of controlled substances
      prescriptions are used to examine trends in state-wide adverse events related to
      methadone. From 1997 to 2004, population-adjusted methadone prescriptions
      increased 727%, with evidence to suggest the rise in the methadone prescription
      rate is for treatment of pain, not addiction therapy. During the same period of
      time, population adjusted, accidental methadone-related deaths in medical
      examiner data increased 1770%. Population adjusted methadone-related emergency
      department encounters rose 612% from 1997 to 2003. Our results suggest that the
      increase in methadone prescription rates from 1997 to 2004 was accompanied by a
      concurrent increase in methadone-related morbidity and mortality. Although
      patient data is not linked between data sources, our results demonstrate that
      utilizing multiple public health data sources captures more cases and provides
      more clinical detail than individual data sources alone. Our approach is a
      successful biomedical informatics approach for surveillance of adverse events and
      utilizes widely available public health data sources, as well as an emerging
      source of public health data, controlled substance prescription registries.

PMID- 17185043
TI  - A rationale and method for high-intensity progressive resistance training with
      children and adolescents.
AB  - BACKGROUND: The rising prevalence of obesity in children and adolescents is
      implicated in the metabolic abnormalities that track into adulthood. The
      associated increased incidence of insulin resistance, metabolic syndrome and type
      2 diabetes being identified in younger cohorts has given rise to a critical
      global health issue. Muscular strength is a vital component of metabolic fitness
      that provides protection from insulin resistance in adults, and we have recently
      shown this to be true in children as well. Targeting muscular strength
      deficiencies at an early age may be an effective preventative strategy for
      metabolic syndrome and type 2 diabetes. PURPOSE: There is limited evidence-based
      best practice for progressive resistance training (PRT), adiposity and metabolic
      fitness in children and adolescents. The purpose of this paper is to describe the
      methodology we utilized for implementing a PRT program to avoid publication bias,
      enable replication of the study and share a novel program that we have found safe
      and suitable for use with youth. METHODS: We conducted the first randomized
      controlled trial (RCT) prescribing high-intensity PRT to children and adolescents
      (10-15 years) as a community-based primary prevention program to address
      adiposity and metabolic health. Participants were instructed to complete 2 sets
      of 8 repetitions of 11 exercises targeting all the major muscle groups twice a
      week at an RPE of 15-18 for 8 weeks. RESULTS: Primary outcome was waist
      circumference; secondary outcomes included insulin resistance, lipid levels,
      muscle strength, cardiorespiratory fitness, body composition, self-efficacy, self
      concept, habitual physical activity, nutritional and sedentary behavior patterns.
      CONCLUSION: The supervised PRT program that we used with children and adolescents
      has been described in detail. The efficacy of this modality of exercise for
      metabolic fitness and other health outcomes is now under investigation.

PMID- 17185044
TI  - Neuroendocrine secretory protein 55 (NESP55) immunoreactivity in male and female
      rat superior cervical ganglion and other sympathetic ganglia.
AB  - Neuroendocrine secretory protein 55 (NESP55) is a soluble, acidic and heat-stable
      protein, belonging to the class of chromogranins. It is expressed specifically in
      endocrine cells and the nervous system, and is probably involved in both
      constitutive and regulated secretion. In the present study, we investigated the
      distribution of NESP55 in various rat sympathetic ganglia by
      immunohistochemistry. The expression of NESP55-IR was detected in a subpopulation
      of principal neurons in the rat SCG, which was also TH positive, and, thus,
      adrenergic. In the rat stellate ganglion, more than two thirds of NESP55 positive
      neurons were adrenergic. Colocalization of NESP55 and calcitonin gene-related
      peptide (CGRP) in cholinergic neurons was also observed. In the rat thoracic
      chain, however, the majority of NESP55 positive neurons appeared to lack TH. No
      detectable NESP55-IR was found in the mouse SCG. Furthermore, in the sexually
      dimorphic SCG, it was demonstrated that, 80% of the NESP55 positive principal
      neurons were also NPY positive in the male rat, while a slightly higher, but
      statistically significant proportion, 87%, was found in the female. Whether or
      not this small difference is physiologically significant is unknown. The present
      data provide basic knowledge about the expression of NESP55 in the sympathetic
      autonomic nervous system of rat, which may further our understanding of the
      functional significance of NESP55.

PMID- 17185045
TI  - The expression pattern and cellular localisation of Myosin VI during the
      Drosophila melanogaster life cycle.
AB  - Myosin VI is a motor protein which is necessary for the morphogenesis of
      epithelial tissues during Drosophila development. The spatial and temporal
      expression of Myosin VI was examined by expressing a GFP (Green Fluorescent
      Protein) tagged Myosin VI molecule (PGM), under the control of a Myosin VI-Gal4
      line. PGM was present in tissues that were shown previously to express Myosin VI,
      such as the ovarian follicle epithelium, and the individualization complex; and
      in other tissues, including the trachea, the midgut, the salivary glands and the
      imaginal discs. The GFP-tagged Myosin V1 rescued the male sterile phenotype of
      Jaguar showing it is functional in vivo. Within individual cells, the role of the
      head and neck domain and the tail domain in targeting of the Myosin V1 molecule
      was examined by investigating the localisation of the separate domains tagged to
      GFP. In salivary glands and follicle cells the head and neck domains were
      concentrated in the cell nucleus, where the minus end of each actin filament is
      located. We found that the tail domain anchors the whole molecule outside of the
      nucleus. Similarly, in the individualization complex in the testes, the tail
      anchors the whole molecule to the base of the complex while the separated head
      with neck domain becomes scattered along the entire actin molecule suggesting the
      cellular location may be determined by cargo proteins that bind to the tail
      domain rather than by the movement of Myosin VI along the actin filaments.

PMID- 17185046
TI  - Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor
      cells of the developing endocrine pancreas.
AB  - The mammalian pancreas develops by the expansion and morphogenesis of the
      epithelial cells of the foregut endoderm via the sequential activation of
      transcription factors that direct differentiation into the various pancreatic
      lineages. Implicit in this growth and differentiation are the temporal and
      spatial processes of cell migration and three-dimensional organization, which
      cooperate to form a properly functioning organ. In many organ systems, such as
      the kidney, heart, and neural crest derivatives, migration and tissue
      morphogenesis is accomplished by the transient conversion of stationary
      epithelial cells to migratory mesenchymal-like cells in a process known as
      epithelial-mesenchymal transition (EMT). We report the identification of the
      expression of the transcription factor Snail2/Slug, a known inducer of EMT and
      cell movement, in both the endocrine and exocrine cells of the developing mouse
      pancreas. Snail2 is expressed in Neurogenin3-positive endocrine progenitor cells,
      and expression is maintained during endocrine cell differentiation where it
      becomes increasingly restricted to the insulin-producing beta cells and
      somatostatin-producing delta cells. In the adult pancreas, the expression of
      Snail2 is maintained at low but detectable levels in all beta cells, indicating a
      latent role for Snail2 in the mature islet. These findings of Snail2 expression
      during endocrine pancreas development are relevant to the recent evidence
      demonstrating the involvement of EMT in the expansion of human islet tissue in
      vitro. EMT-like events appear to be involved in the development of the mammalian
      pancreas in vivo.

PMID- 17185048
TI  - Gene expression microarrays and respiratory muscles.
AB  - The routine measurement of the expression of tens of thousands of gene
      transcripts, simultaneously, is a defining advance of the last decade which has
      been made possible by microarray technology. Using this very powerful approach, a
      pattern has emerged from a number of studies that suggest a molecular niche for
      the diaphragm which is quite different from that occupied by limb muscle. All
      indications are that this is true not only in regard to differential gene
      transcription patterns in healthy muscles but also in the changes in
      transcription occurring in association with different diseases. Furthermore,
      respiratory muscle mounts a rich gene expression response to a number of
      disturbances, be they primary genetic defects (e.g. various types of muscular
      dystrophies) or non-genetic perturbations (e.g. controlled mechanical
      ventilation). Large numbers of genes undergo altered levels of transcription,
      ranging from tens to hundreds (typical) to thousands. These genes are involved in
      diverse cellular processes, such as contraction, intermediate metabolism,
      oxidative stress, apoptosis and cellular adhesion. Functional groups of genes
      identified as having changed expression differ in many respects from one disease
      to another. Previously identified pathways of muscle injury and repair are often
      perturbed to greater extents than previously anticipated, and processes not
      previously suspected of having important roles in the pathophysiology of specific
      disorders have been identified. Elucidation of these under-appreciated molecular
      events may lead to novel therapeutic interventions based on disrupting the
      downstream adverse consequences of the primary event or facilitating events which
      ameliorate the injury and/or promote muscle healing.

PMID- 17185047
TI  - Dry powder inhalation of colistin in cystic fibrosis patients: a single dose
      pilot study.
AB  - BACKGROUND: Dry powder inhalation (DPI) may be an alternative to nebulisation of
      drugs in the treatment of chest infections in cystic fibrosis (CF) patients. In a
      pilot study the feasibility of a colistin dry powder inhaler (prototype Twincer)
      by a single dose in CF-patients was assessed and compared to nebulised colistin.
      METHODS: Ten CF-patients, chronically infected with P. aeruginosa, participated
      in a randomised cross over study. On two visits to the outpatient clinic,
      patients inhaled colistin sulphomethate as 25 mg dry powder (Twincer) or as 158
      mg nebulised solution (Ventstream nebuliser, PortaNeb compressor). Pulmonary
      function tests were performed before, 5 and 30 min after inhalation. Serum
      samples were drawn prior to each dose and at 15, 45 min, 1.5; 2.5; 3.5 and 5.5 h
      after inhalation. RESULTS: The DPI was well tolerated by the patients: no
      significant reduction in FEV1 was observed. Relative bioavailability of DPI to
      nebulisation was approx. 140% based on actual dose and approx. 270% based on drug
      dose label claim. CONCLUSIONS: The colistin DPI (Twincer inhaler) is well
      tolerated and appreciated by CF-patients. Optimisation with respect to particle
      size and internal resistance of the inhaler is necessary to attain equivalent
      pulmonary deposition to liquid nebulisation.

PMID- 17185050
TI  - Sensitive quantification of rifaximin in human plasma by liquid chromatography
      tandem mass spectrometry.
AB  - A liquid chromatography-mass spectrometry method (LC-MS/MS) for the quantitative
      determination of rifaximin in human plasma was developed and validated. In the
      developed procedure, metoprolol was added to human plasma as an internal standard
      (IS) and acetonitrile was used to precipitate the plasma proteins before LC-MS/MS
      analysis. Chromatographic separation was obtained on a RESTEK Pinnacle C18 column
      (50 mm x 2.1mm, 5 microm) with a mobile phase consisted of ammonium acetate
      solution (15 mM, pH 4.32) as buffer A and methanol as mobile phase B.
      Quantification was performed in positive mode using multiple reaction monitoring
      (MRM) of the transitions m/z 786.1-->754.1 for rifaximin and m/z 268.3-->116.1
      for the IS. The assay has been validated over the concentration range of 0.5-10
      ng/ml (r=0.9992) based on the analysis of 0.2 ml of plasma. The assay accuracy
      was between 98.2% and 109%. The within-day and between-day precision was better
      than 3.9% and 8.9% at three concentration levels. The freeze-thaw stability was
      also investigated and it was found that both rifaximin and the IS were quite
      stable. This method provides a rapid, sensitive, specific and robust tool for the
      quantitative determination of rifaximin in human plasma, which is especially
      useful for the pharmacokinetic study of rifaximin.

PMID- 17185049
TI  - Achiral-chiral LC/LC-FLD coupling for determination of carvedilol in plasma
      samples for bioequivalence purposes.
AB  - Bioequivalence data for two pharmaceutical formulations (solid oral dosage forms)
      containing carvedilol is presented for both racemic and enantiomers of the active
      substance. This was achieved by on-line coupling of two liquid chromatographic
      separations followed by fluorescence detection. The first LC dimension was used
      for a fast separation of racemic carvedilol from propranolol (IS) and the
      endogenous matrix, by means of a reversed phase mechanism. The peak of racemic
      carvedilol was on-line transferred to the second enantioselective LC dimension,
      based on a reversed phase separation on cellulose tris(3,5-dimethyl
      phenylcarbamate) stationary phase. Both stages were monitored over a single run
      by means of a fluorescence detector operated at an excitation wavelength of 285
      nm and an emission wavelength of 355 nm. Automated shortcutting of the racemic
      carvedilol peak to the chiral column and simultaneous detection over the two LC
      dimensions have been obtained by using an experimental set-up based on two six
      port rotative switching valves. Linearity was demonstrated on the interval 2-150
      ng/mL for racemic carvedilol and on 1-75 ng/mL intervals for enantiomers. LLOQ
      fits between 0.7 and 1.4 ng/mL. Recoveries of the target compounds are 87+/-4 and
      81+/-4% for the IS. Precision ranged from 0.6 to 2.5% and the mean accuracy
      obtained on quality control samples (measured as % bias) over the whole study
      falls between -0.8 and 6.3%.

PMID- 17185051
TI  - Inactivation of alcohol dehydrogenase (ADH) by ferryl derivatives of human
      hemoglobin.
AB  - In this paper, inactivation of alcohol dehydrogenase (ADH) by products of
      reactions of H2O2 with metHb has been studied. Inactivation of the enzyme was
      studied in two systems corresponding to two kinetic stages of the reaction. In
      the first system H2O2 was added to the mixture of metHb and ADH [the
      (metHb+ADH)+H2O2] system (ADH was present in the system since the moment of
      addition of H2O2 i. e. since the very beginning of the reaction of metHb with
      H2O2). In the second system ADH was added to the system 5 min after the
      initiation of the reaction of H2O2 with metHb [the (metHb+H2O2)5 min+ADH] system.
      In the first case all the products of reaction of H2O2 with metHb (non-peroxyl
      and peroxyl radicals and non-radical products, viz. hydroperoxides and
      *HbFe(IV)=O) could react with the enzyme causing its inactivation. In the second
      system, enzyme reacted almost exclusively with non-radical products (though a
      small contribution of reactions with peroxyl radicals cannot be excluded). ADH
      inactivation was observed in both system. Hydrogen peroxide alone did not
      inactivate ADH at the concentrations employed evidencing that enzyme inactivation
      was due exclusively to products of reaction of H2O2 with metHb. The rate and
      extent of ADH inactivation were much higher in the first than in the second
      system. The dependence of ADH activity on the time of incubation with ferryl
      derivatives of Hb can be described by a sum of three exponentials in the first
      system and two exponentials in the second system. Reactions of appropriate forms
      of the ferryl derivatives of hemoglobin have been tentatively ascribed to these
      exponentials. The extent of the enzyme inactivation in the second system was
      dependent on the proton concentration, being at the highest at pH 7.4 and
      negligible at pH 6.0. The reaction of H2O2 with metHb resulted in the formation
      of cross-links of Hb subunits (dimers and trimers). The amount of the dimers
      formed was much lower in the first system i. e. when the radical forms dominated
      the reaction of inactivation.

PMID- 17185052
TI  - Proteome analysis of Halobacterium salinarum and characterization of proteins
      related to the degradation of isopropyl alcohol.
AB  - We reported in a previous study that proteomic approach, coupled with genomic
      techniques, could be used to screen and develop multiple candidates for
      halophilic enzymes from Halobacterium salinarum. In order to evaluate the
      biodegradation of isopropyl alcohol (IPA) by H. salinarum, the amounts of
      residual IPA and acetone generated in the growth media were determined using a
      gas chromatography-flame ionization detector (GC-FID). The protein expression
      profiles of cells which had been cultured with IPA were obtained with the two
      dimensional gel electrophoresis. Proteins evidencing different expression levels
      in the presence of 0.5% IPA were identified by electrospray ionization-quadruple
      time of flight (ESI-Q-TOF) mass spectrometry. We found 12 proteins which were
      down-regulated, and another 12 proteins which were up-regulated, in the presence
      of 0.5% IPA and we further identified 17 proteins among them using ESI-TOF MS/MS.
      Among these identified proteins, we selected glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) for further characterization as a halophilic enzyme. We
      have demonstrated for the first time that H. salinarum possesses the ability to
      degrade IPA and GAPDH was both stable and active at high salt concentrations,
      with maximum activity occurring at 1 M NaCl, although the optimal salt
      concentration with regard to the growth of H. salinarum is 4.3 M.

PMID- 17185053
TI  - Enteral nutrition for premature infants: the role of human milk.
AB  - Nutrition support of the premature infant must be designed to compensate for
      metabolic and gastrointestinal immaturity, immunologic insufficiency, and the
      demands of associated medical conditions. The beneficial effects of human milk
      extend to the feeding of premature infants. Although human milk enhances
      immunity, nutritional concerns arise because the milk might not meet the expanded
      nutrient requirements of very low birth weight premature infants. Human milk
      fortifiers are available to provide optimum nutrition. This chapter summarizes
      the benefits and limitations of human milk for the premature infant.

PMID- 17185054
TI  - Pure partial trisomy of 6p12.1-p22.1 secondary to a familial 12/6 insertion in
      two malformed babies.
AB  - We describe two malformed infants with trisomy 6p12.1-p22.1 due to 12/6
      interchromosomal insertion. The phenotypic data observed in these patients are
      compared chiefly with a case cytogenetically similar described by Villa et al.
      [A. Villa, E.G. Gomez, L. Rodriguez, R.H. Rastrollo, M.E. Martinez Tallo, M.L.
      Martinez-Frias, Interstitial tandem duplication of 6p: a case with partial
      trisomy (6)(p12p21.3), Am. J. Med. Genet. 90 (2000) 369-375]. All three infants
      are trisomic for a genomic segment which largely overlaps that reported as
      duplicated in previous cases, but with the addition of a more proximal segment,
      extending from 6p12 to 6p21. We suggest that some of their phenotypic anomalies
      are due to the trisomy of this chromosomal region. We also speculate on the
      possible role played by the TFAP2B (Transcription Factor AP2-beta) gene, which is
      one of the genes mapped on the duplicated segment.

PMID- 17185055
TI  - A novel locus on the X chromosome regulates post-maturity bone density changes in
      mice.
AB  - Two mouse strains, AKR/J and SAMP6, were assessed longitudinally for bone mineral
      density of the spine. They displayed very different time courses of bone accrual,
      with the SAMP6 strain reaching a plateau for vertebral BMD at 3 months, whereas
      AKR/J mice continued to increase spine BMD for at least 8 months. Among 253 F(2)
      progeny of an AKR/JxSAMP6 cross, at 4 months of age, the BMD variance was 5-6% of
      the mean, vs. 15% for weight. Variance increased with age for every parameter
      measured, and was generally higher among males. The ratio of 6-month/4-month
      spine BMDs, termed DeltasBMD, had a normal distribution with 5.7% variance, and
      was largely independent of spine BMD (R=-0.23) or body weight (R=-0.12) at
      maturity. Heritability of the DeltasBMD trait was calculated at 0.59. Genetic
      mapping identified two significant loci, both distinct from those observed for
      BMD at maturity--implying that different genes regulate skeletal growth vs.
      remodeling. A locus on the X chromosome, replicated in two mouse F(2) populations
      (P<10(-4) for combined discovery and confirmation), affects age-dependent BMD
      change for both spine and the full skeleton. Its position agrees with a very
      narrow region identified by association mapping for effects on lumbar bone
      density in postmenopausal women [Parsons CA, Mroczkowski HJ, McGuigan FE, Albagha
      OM, Manolagas S, Reid DM, et al. Interspecies synteny mapping identifies a
      quantitative trait locus for bone mineral density on human chromosome Xp22. Hum
      Mol Genet 2005;14:3141-8]. A second locus, on chromosome 7, was observed in only
      one cross. Single-nucleotide polymorphisms (SNPs) are highly clustered near these
      loci, distinguishing the parental strains over only limited spans.

PMID- 17185057
TI  - Overview of orofacial pain: epidemiology and gender differences in orofacial
      pain.
AB  - Chronic orofacial pain is a prevalent problem that encompasses numerous disorders
      with diverse causes and presenting symptoms. Compared with men, women of
      reproductive age seek treatment for orofacial pain conditions, as well as other
      chronic pain disorders more frequently. Important issues have been raised
      regarding gender and sex differences in genetic, neurophysiologic, and
      psychosocial aspects of pain sensitivity and analgesia. Efforts to improve our
      understanding of qualitative sex differences in pain modulation signify a
      promising step toward developing more tailored approaches to pain management.

PMID- 17185059
TI  - Central mechanisms of orofacial pain.
AB  - The orofacial pain clinician must understand the difference between peripheral
      and central mechanisms of pain. Particularly, one has to understand the process
      of central sensitization as it relates to the various orofacial pain conditions
      to understand orofacial pain. Understanding leads to more effective treatment.

PMID- 17185058
TI  - Peripheral mechanisms of odontogenic pain.
AB  - In this article, we review the key basic mechanisms associated with this
      phenomena and more recently identified mechanisms that are current areas of
      interest. Although many of these pain mechanisms apply throughout the body, we
      attempt to describe these mechanisms in the context of trigeminal pain.

PMID- 17185061
TI  - Joint intracapsular disorders: diagnostic and nonsurgical management
      considerations.
AB  - This article reviews common intracapsular temporomandibular disorders encountered
      in the dental practice. It begins with a brief review of normal temporomandibular
      joint anatomy and function followed by a description of the common types of
      disorders known as internal derangements. The etiology, history, and clinical
      presentation of each are reviewed. Nonsurgical management is presented based on
      current long-term scientific evidence.

PMID- 17185060
TI  - Myogenous temporomandibular disorders: diagnostic and management considerations.
AB  - Myogenous temporomandibular disorders (or masticatory myalgia) are characterized
      by pain and dysfunction that arise from pathologic and functional processes in
      the masticatory muscles. There are several distinct muscle disorder subtypes in
      the masticatory system, including myofascial pain, myositis, muscle spasm, and
      muscle contracture. The major characteristics of masticatory myalgia include
      pain, muscle tenderness, limited range of motion, and other symptoms (eg,
      fatigability, stiffness, subjective weakness). Comorbid conditions and
      complicating factors also are common and are discussed. Management follows with
      stretching, posture, and relaxation exercises, physical therapy, reduction of
      contributing factors, and as necessary, muscle injections.

PMID- 17185062
TI  - Temporomandibular disorders: associated features.
AB  - Temporomandibular disorder (TMD) encompasses a number of clinical problems
      involving the masticatory muscles or the temporomandibular joints. These
      disorders are a major cause of nondental pain in the orofacial region, and are
      considered to be a subclassification of musculoskeletal disorders. Orofacial pain
      and TMD can be associated with pathologic conditions or disorders related to
      somatic and neurologic structures. When patients present to the dental office
      with a chief complaint of pain or headaches, it is vital for the practitioner to
      understand the cause of the complaint and to perform a thorough examination that
      will lead to the correct diagnosis and appropriate treatment. A complete
      understanding of the associated medical conditions with symptomology common to
      TMD and orofacial pain is necessary for a proper diagnosis.

PMID- 17185063
TI  - Temporomandibular disorders and headache.
AB  - Headache is a common symptom, but when severe, it may be extremely disabling. It
      is assumed that patients who present to dentists with headache often are
      diagnosed with a temporomandibular disorder (TMD), although many may have
      migraine. TMD as a collective term may include several clinical entities,
      including myogenous and arthrogenous components. Because headache and TMD are so
      common they may be integrated or separate entities. Nevertheless, the
      temporomandibular joint (TMJ) and associated orofacial structures should be
      considered as triggering or perpetuating factors for migraine. This article
      discusses the relationship between the TMJ, muscles, or other orofacial
      structures and headache.

PMID- 17185064
TI  - Psychological factors associated with orofacial pains.
AB  - This article develops the case for why trigeminal pain is a unique and
      challenging problem for clinicians and patients alike, and provides the reader
      with insights for effective trigeminal pain management based on an understanding
      of the interplay between psychologic and physiologic systems. There is no greater
      sensory experience for the brain to manage than unremitting pain in trigeminally
      mediated areas. Such pain overwhelms conscious experience and focuses the
      suffering individual like few other sensory events. Trigeminal pain often
      motivates a search for relief that can drain financial and emotional resources.
      In some instances, the search is rewarded by a treatment that immediately
      addresses an identifiable source of pain; in other cases, it can stimulate never
      ending pilgrimages from one health provider to another.

PMID- 17185065
TI  - Temporomandibular disorders, head and orofacial pain: cervical spine
      considerations.
AB  - Head and orofacial pain originates from dental, neurologic, musculoskeletal,
      otolaryngologic, vascular, metaplastic, or infectious disease. It is treated by
      many health care practitioners, such as dentists, oral surgeons, and physicians.
      The article focuses on the nonpathologic involvement of the musculoskeletal
      system as a source of head and orofacial pain. The areas of the musculoskeletal
      system that are reviewed include the temporomandibular joint and muscles of
      mastication--collectively referred to as temporomandibular disorders (TMDs) and
      cervical spine disorders. The first part of the article highlights the role of
      physical therapy in the treatment of TMDs. The second part discusses cervical
      spine considerations in the management of TMDs and head and orofacial symptoms.
      It concludes with and overview of the evaluation and treatment of the cervical
      spine.

PMID- 17185066
TI  - Temporomandibular joint surgery for internal derangement.
AB  - Surgery of the temporomandibular joint (TMJ) plays a small, but important, role
      in the management of patients who have temporomandibular disorders (TMDs). There
      is a spectrum of surgical procedures for the treatment of TMD that ranges from
      simple arthrocentesis and lavage to more complex open joint surgical procedures.
      It is important to recognize that surgical treatment rarely is performed alone;
      generally, it is supported by nonsurgical treatment before and after surgery.
      Each surgical procedure should have strict criteria for which cases are most
      appropriate. Recognizing that scientifically proven criteria are lacking, this
      article discusses the suggested criteria for each procedure, ranging from
      arthrocentesis to complex open joint surgery. The discussion includes
      indications, brief descriptions of techniques, outcomes, and complications for
      each procedure.

PMID- 17185067
TI  - Neuropathic orofacial pain: proposed mechanisms, diagnosis, and treatment
      considerations.
AB  - The most common reason patients seek medical or dental care in the United States
      is due to pain or dysfunction. The orofacial region is plagued by a number of
      acute, chronic, and recurrent painful maladies. Pain involving the teeth and the
      periodontium is the most common presenting concern in dental practice. Non
      odontogenic pain conditions also occur frequently. Recent scientific
      investigation has provided and explosion of knowledge regarding pain mechanisms
      and pathways and an enhanced understanding of the complexities of the many
      ramifications of the total pain experience. Therefore, it is mandatory for the
      dental professional to develop the necessary clinical and scientific expertise on
      which he/she may base diagnostic and management approaches. Optimum management
      can be achieved only by determining an accurate and complete diagnosis and
      identifying all of the factors associated with the underlying pathosis on a case
      specific basis. A thorough understanding of the epidemiologic and etiologic
      aspects of dental. musculoskeletal, neurovascular, and neuropathic orofacial pain
      conditions is essential to the practice of evidence-based dentistry/medicine.

PMID- 17185068
TI  - Four oral motor disorders: bruxism, dystonia, dyskinesia and drug-induced
      dystonic extrapyramidal reactions.
AB  - This article reviews four of the involuntary hyperkinetic motor disorders that
      affect the orofacial region: bruxism, orofacial dystonia, oromandibular
      dyskinesia, and medication-induced extrapyramidal syndrome-dystonic reactions. It
      discusses and contrasts the clinical features and management strategies for
      spontaneous, primary, and drug-induced motor disorders in the orofacial region.
      The article provides a list of medications that have been reported to cause drug
      related extrapyramidal motor activity, and discusses briefly the genetic and
      traumatic events that are associated with spontaneous dystonia. Finally, it
      presents an approach for management of the orofacial motor disorders. The
      contraindications, side effects, and usual approach for medications and
      injections are covered. An overview of the indications, contraindications, and
      complications of using botulinum toxin as a therapeutic modality is discussed
      briefly.

PMID- 17185069
TI  - A critical review of the use of botulinum toxin in orofacial pain disorders.
AB  - This article reviews the appropriate use, cautions, and contraindication for
      botulinum neurotoxin (BoNT) and reviews the peer-reviewed literature that
      describes its efficacy for treatment of various chronic orofacial pain disorders.
      The literature has long suggested that BoNT is of value for orofacial
      hyperactivity and more recently for some orofacial pain disorders; however, the
      results are not as promising for orofacial pain. The available data from
      randomized, double-blind, placebo-controlled trials (RBCTs) do not support the
      use of BoNT as a substantially better therapy than what is being used already.
      The one exception is that BoNT has reasonable RBCT data to support its use as a
      migraine prophylaxis therapy. The major caveat is that the use of BoNT in chronic
      orofacial pain is "off-label".

PMID- 17185070
TI  - Complementary and alternative medicine for persistent facial pain.
AB  - This article discusses complementary and alternative medicine (CAM), reviews
      literature on the prevalence of use of CAM by the general adult population in the
      United States and by patients with persistent facial pain, and summarizes
      published, peer-reviewed reports of clinical trials assessing the effects of CAM
      therapies for persistent facial pain. Results indicate that many patients use CAM
      for musculoskeletal pain, including persistent facial pain. Preliminary work on
      selected complementary therapies such as biofeedback, relaxation, and acupuncture
      seems promising; however, there are more unanswered than answered questions about
      cost-effectiveness, efficacy and mechanisms of action of CAM for persistent
      facial pain.

PMID- 17185072
TI  - Curative endoscopic resection of early esophageal adenocarcinomas (Barrett's
      cancer).
AB  - BACKGROUND: In view of the increasing incidence of adenocarcinoma in Barrett's
      esophagus and the mortality and high morbidity rates associated with surgical
      therapy for this condition, safe and effective but less invasive methods of
      treatment are needed. OBJECTIVE: To evaluate efficacy and safety of endoscopic
      resection in these patients. DESIGN: Single-center prospective study. SETTING:
      Teaching hospital, conducted between October 1996 and September 2003. PATIENTS: A
      total of 100 consecutive patients (mean age, 62.1 +/- 10.9 years; range, 31-86
      years) with low-risk adenocarcinoma of the esophagus (macroscopic types I, IIa,
      IIb, and IIc; lesion diameter up to 20 mm; mucosal lesion without invasion into
      lymph vessels and veins; and histologic grades G1 and G2) arising in Barrett's
      metaplasia. INTERVENTIONS: Endoscopic resection with the suck-and-cut technique.
      MAIN OUTCOME MEASUREMENTS: Complete local remission. RESULTS: A total of 144
      resections (1.47 per patient) were performed without technical problems. No major
      complications and only 11 minor ones (bleedings without decrease of Hb >2 g/dL;
      treated with injection therapy) occurred. Complete local remission was achieved
      in 99 of the 100 patients after 1.9 months (range, 1-18 months) and a maximum of
      3 resections. During a mean follow-up period of 36.7 months, recurrent or
      metachronous carcinomas were found in 11% of the patients, but successful repeat
      treatment with endoscopic resection was possible in all of these cases. The
      calculated 5-year survival rate was 98%. Two patients died of other causes.
      LIMITATIONS: Nonblinded, nonrandomized study. CONCLUSIONS: Endoscopic resection
      is associated with favorable outcomes for low-risk patients with early esophageal
      adenocarcinoma (Barrett's carcinoma).

PMID- 17185073
TI  - Endoscopic resection for treatment of mucosal Barrett's cancer: time to swing the
      pendulum.

PMID- 17185074
TI  - EMR for intramucosal adenocarcinoma of the esophagus: does one size fit all?

PMID- 17185075
TI  - Does cancer risk affect health-related quality of life in patients with Barrett's
      esophagus?
AB  - BACKGROUND: Health-related quality of life is decreased in patients with GERD and
      Barrett's esophagus (BE). OBJECTIVE: To determine whether time-tradeoff (TTO)
      values would differ in patients with BE when patients were asked to trade away
      the potential risk of esophageal adenocarcinoma rather than chronic heartburn
      symptoms. DESIGN: A prospective clinical trial. PATIENTS: Subjects with biopsy
      proven BE. INTERVENTIONS: Custom-designed computer program to elicit health-state
      utility values, quality of life in reflux and dyspepsia (QOLRAD), and Medical
      Outcomes Survey short form-36 surveys. MAIN OUTCOME MEASUREMENTS: TTO utility
      values for the annual cancer-risk-associated current health state and for
      hypothetical scenarios of dysplasia and esophageal cancer. RESULTS: We studied 60
      patients in the cancer-risk cohort (57 men, 92% veteran; mean age [standard
      deviation; SD], 65 years [11 years], mean GERD duration 17 years [12 years]). The
      heartburn cohort included 40 patients with GERD and BE with TTO values derived
      for GERD symptoms. The mean (SD) utility for nondysplastic BE was 0.91 (0.13)
      compared with 0.90 (0.12) for the heartburn cohort (P = .7). The mean utility
      values were significantly lower for scenarios of low-grade dysplasia (0.85
      [0.12], P = .02) and high-grade dysplasia (0.77 [0.14], P < .005). The mean TTO
      was 0.67 (0.19) for the scenario of esophageal cancer. There was no correlation
      between the utility scores and the disease-specific survey scores. LIMITATIONS:
      TTO values were hypothetical for states of dysplasia and cancer. CONCLUSIONS: TTO
      utility values based on heartburn symptoms or annual risk of cancer in patients
      with nondysplastic BE are roughly equivalent. However, TTO utility values are
      significantly lower for health states with increasing cancer risks.

PMID- 17185077
TI  - Barrett's esophagus and the costs of "doing something".

PMID- 17185076
TI  - Patients with Barrett's esophagus perceive their risk of developing esophageal
      adenocarcinoma as low.
AB  - BACKGROUND: The risk of developing esophageal adenocarcinoma (EAC) for patients
      with Barrett's esophagus (BE) is approximately 0.5% per year. OBJECTIVE: To
      investigate how patients with BE estimate and perceive their risk of developing
      EAC. DESIGN: Questionnaire study. SETTING: Patients with BE who were undergoing
      surveillance endoscopy based on histologic and flow cytometric results. PATIENTS:
      A total of 192 patients with BE were included. MAIN OUTCOME MEASUREMENTS:
      Individual patients were asked to estimate the numerical risk to develop EAC for
      patients with BE in general and for themselves. How patients perceived their own
      risk was measured on a scale from "very small" to "very large." RESULTS: At least
      1 question was filled out by 169 patients (88% response). Sixty percent of
      respondents underestimated the numerical risk for patients with BE, in general,
      to develop EAC, while even more patients (69%) underestimated their own risk.
      Most respondents perceived their own risk as very small or small (63%).
      LIMITATIONS: Risk estimations may depend on the response scale used. CONCLUSIONS:
      Most patients with BE underestimated the numerical risk and perceived their risk
      of developing EAC as (very) low. Despite a low perceived risk, all patients in
      this group adhered to endoscopic surveillance.

PMID- 17185078
TI  - Usefulness of magnifying endoscopy with narrow band imaging for the detection of
      specialized intestinal metaplasia in columnar-lined esophagus and Barrett's
      adenocarcinoma.
AB  - BACKGROUND: Barrett's esophagus with specialized intestinal metaplasia (SIM) from
      columnar-lined esophagus is difficult to distinguish with routine endoscopy.
      OBJECTIVE: To examine the values of fine mucosal patterns and the capillary
      patterns observed by magnifying endoscopy with narrow band imaging (MENBI) for
      the detection of SIM in columnar-lined esophagus and superficial Barrett's
      adenocarcinoma. We also undertook a histologic investigation regarding whether
      the capillary pattern observed by MENBI corresponds to the 3-dimensional (3D)
      structure of the capillary as depicted by using a confocal laser-scanning
      microscope (CLSM). DESIGN: To compare the findings of MENBI, at 217 sites of
      columnar-lined esophagus, with histologic findings. Capillaries of the
      superficial mucosal layer were observed and were analyzed by 3D with a CLSM in 45
      biopsied specimens. PATIENTS: Fifty-eight patients, including 4 with superficial
      Barrett's adenocarcinoma. SETTING: Jikei University Hospital, Tokyo, Japan.
      RESULTS: Upon observation, all 6 adenocarcinoma sites were classified as
      irregular patterns in both the fine mucosal patterns and capillary patterns. The
      most characteristic endoscopic patterns of SIM were revealed to be the
      cerebriform fine mucosal pattern (sensitivity, 56%; specificity, 79%; odds ratio,
      4.78) and ivy- or deoxyribonucleic acid (DNA)-like capillary pattern
      (sensitivity, 77%; specificity, 94%; odds ratio, 51.6). The addition of capillary
      patterns to fine mucosal patterns improved the accuracy of diagnosing SIM (P <
      .0001). CONCLUSIONS: MENBI was able to precisely visualize the structure of
      capillaries in the superficial mucosal layer. The addition of capillary patterns
      to fine mucosal patterns appeared to improve the diagnostic value for detecting
      SIM and superficial Barrett's adenocarcinoma upon observation by MENBI.

PMID- 17185079
TI  - Narrow band imaging in Barrett's esophagus--where are we standing?

PMID- 17185080
TI  - Predictors of stricture formation after photodynamic therapy for high-grade
      dysplasia in Barrett's esophagus.
AB  - BACKGROUND: Stricture formation is the leading cause of long-term morbidity after
      photodynamic therapy (PDT). Risk factors for stricture formation have not been
      studied. OBJECTIVE: To assess risk factors for stricture formation in patients
      undergoing PDT for Barrett's esophagus with high-grade dysplasia (HGD). DESIGN:
      Retrospective cohort study. SETTING: Barrett's Unit, Mayo Clinic, Rochester,
      Minnesota. METHODS: Records of patients undergoing PDT for HGD were reviewed.
      Patients underwent PDT by using either bare cylindrical diffusing fibers (2.5-5.0
      cm in length) or balloon diffusers with 5- to 7-cm windows. Univariate and
      multivariate logistic regression analyses were performed to assess risk factors
      for stricture formation. MAIN OUTCOME MEASUREMENT: Esophageal stricture
      formation. RESULTS: Thirty-five of 131 patients (27%) developed strictures. On
      multivariate analysis, statistically significant predictors of stricture
      formation were the following: EMR before PDT was odds ratio (OR) 2.7, 95%
      confidence interval (CI) 1.13-6.59; a prior history of esophageal stricture was
      OR 2.7, 95% CI 1.15-6.47; and the number of PDT applications was OR 2.2, 95% CI
      1.22-4.12. The OR for stricture formation in patients when centering balloons
      were used was 0.41, 95% CI 0.11-1.46, P = .168, indicating that centering
      balloons did not significantly decrease the risk of stricture formation.
      LIMITATIONS: Retrospective single-center study; small proportion of patients
      treated with centering balloons. CONCLUSIONS: Risk factors for development of
      strictures after PDT included history of a prior esophageal stricture,
      performance of EMR before PDT, and more than 1 PDT application in 1 treatment
      session. The use of centering balloons was not associated with a statistically
      significant reduction in the risk of stricture formation.

PMID- 17185081
TI  - Photodynamic therapy strictures: who is at risk?

PMID- 17185083
TI  - Stents for palliating malignant dysphagia and fistula: is the paradigm shifting?

PMID- 17185082
TI  - Evolving role of self-expanding metal stents in the treatment of malignant
      dysphagia and fistulas.
AB  - BACKGROUND: Self-expanding metal stents (SEMS) are touted as the cornerstone of
      endoscopic palliation of unresectable esophageal cancer. However, usage at MD
      Anderson has fallen in recent years, despite a greater volume of patients with
      esophageal cancer. OBJECTIVE: To compare our more recent experience with that of
      earlier reported institutional experience and to assess how esophageal stent use
      has evolved. DESIGN: A retrospective chart review. SETTING: A tertiary referral
      cancer center. PATIENTS: Ninety-seven patients with malignant dysphagia who had
      SEMS placed from 2000 to 2003. INTERVENTIONS: Placement of SEMS for malignant
      disease. MAIN OUTCOMES MEASUREMENTS: Dysphagia scores, overall survival, and
      complication rates. RESULTS: Dysphagia scores improved in 86%, and
      tracheoesophageal fistula symptoms improved in 90%. Complications were seen in a
      majority of the patients and major complications in 37%. Ten patients had
      hematemesis, migrations occurred in 5, and early unexpected deaths in 2.
      Adenocarcinoma and female sex were factors associated with increased odds of a
      major complication. Prior chemoradiation, age, stricture location, and length
      were not associated with complications. Median survival was 77 days. LIMITATIONS:
      Noncomparative retrospective single-center study. CONCLUSIONS: SEMS fall short of
      an ideal palliative method, because complications that require additional
      intervention are frequent. Usage has declined despite higher numbers of patients
      with esophageal cancer. However, for patients with tracheoesophageal fistulas,
      SEMS are the treatment of choice. For patients who are not candidates for
      chemoradiation or who failed to achieve adequate palliation with such therapy,
      SEMS offer a viable, albeit imperfect, endoscopic approach.

PMID- 17185084
TI  - Endoscopic screening for varices in cirrhotic patients: data from a national
      endoscopic database.
AB  - BACKGROUND: The current guidelines for primary prophylaxis of variceal hemorrhage
      in cirrhotic patients recommend screening for varices with upper endoscopy (EGD).
      Utilization and outcomes of screening in clinical practice are unknown.
      OBJECTIVE: Our purpose was to determine the use of endoscopic variceal screening
      in diverse practice settings and to determine factors associated with the finding
      of esophageal varices. DESIGN: Endoscopic reports generated by the Clinical
      Outcomes Research Initiative (CORI) repository were analyzed to determine the
      use, changes over time, and findings of screening upper endoscopies between
      January 1, 2000, and December 31, 2003. SETTING: Data from 68 CORI practices (70%
      community/17% academic/13% Veterans Affairs Medical Center [VAMC]) were
      evaluated. PATIENTS: A total of 1688 of 172,854 EGDs were performed for the
      purpose of screening for varices. RESULTS: Overall, there was a linear increase
      in annual proportion of screening EGDs performed (P < .0001). A significantly
      greater proportion of variceal screening EGDs are performed in academic centers
      compared with VAMC and community practices. Varices were found in 881 screened
      patients (52.2%). Varices were found more often in Child-Pugh class B/C (71.9%)
      compared with Child-Pugh class A (42.7%) patients. Of those with varices found,
      patients with Child-Pugh class B/C were more likely to have large varices than
      were patients with Child-Pugh class A (P = .02). LIMITATIONS: A limitation of
      this study was the inability to determine the total number of cirrhotic patients
      cared for at each CORI site included in this study. CONCLUSIONS: Endoscopic
      screening for varices represents a small proportion of all upper endoscopies
      performed. This proportion increased between 2000 and 2003. Varices were found
      more frequently in patients with more severe liver disease.

PMID- 17185085
TI  - The value of EUS in predicting the response of gastric mucosa-associated lymphoid
      tissue lymphoma to Helicobacter pylori eradication.
AB  - BACKGROUND: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is
      associated with Helicobacter pylori infection, and regression of the tumor has
      been described after its eradication. OBJECTIVE: To determine the value of EUS,
      in addition to other clinical/endoscopic features, in predicting the response of
      low-grade MALT lymphoma to H pylori eradication. DESIGN: A retrospective, single
      center study. SETTING AND PATIENTS: Twenty-two patients with primary gastric MALT
      lymphoma were identified through a retrospective review of charts of patients
      seen at the American University of Beirut Medical Center. Only 19 patients with
      histopathologically confirmed gastric MALT lymphoma and H pylori infection who
      had EUS staging were included in the study. MAIN OUTCOME MEASUREMENTS: Regression
      of the gastric MALT lymphoma as determined by follow-up endoscopy and mucosal
      biopsies. RESULTS: Patients with disease restricted to the gastric mucosa had a
      significantly higher rate of complete remission after H pylori eradication
      compared with patients who had disease infiltrating into the gastric submucosa
      (77.8% vs 12.5%, P value .007). There was no statistical difference in terms of
      the mean follow-up time to achieve such response (P value .212). Age, sex,
      location of the tumor within the stomach, and endoscopic appearance did not
      correlate with the probability of complete remission of the MALT lymphoma.
      LIMITATIONS: The limitations include a retrospective design and a relatively
      small sample population. CONCLUSION: EUS determination of the invasion depth of
      gastric MALT lymphoma helps predict a complete response to H pylori eradication.

PMID- 17185086
TI  - EUS to predict cure of gastric mucosa-associated lymphoma after Helicobacter
      pylori eradication.

PMID- 17185087
TI  - Difficulty in diagnosing autoimmune pancreatitis by imaging findings.
AB  - BACKGROUND: Autoimmune pancreatitis (AIP) presents as diffuse enlargement of the
      pancreas and as diffuse irregular narrowing of the main pancreatic duct. However,
      some AIP cases are difficult to diagnose because of atypical imaging findings.
      OBJECTIVE: To clarify a variety of imaging findings of AIP and the reason for its
      misdiagnosis. DESIGN: We examined the imaging findings of 37 AIP cases and also
      examined misdiagnosed cases of AIP to determine their reasons for misdiagnosis.
      PATIENTS: A total of 37 patients with AIP who reported to our hospital or its
      affiliate over a 17-year period (1989 to May 2005). RESULTS: Patients in 15 AIP
      cases showed segmental narrowing of the main pancreatic duct. There were 6
      patients with focal enlargement of the pancreas, whereas 3 patients showed no
      enlargement. There were 3 cases of calcification of the pancreas. Pancreatic
      cysts were detected in 2 patients. Abdominal US showed multiple low-echoic masses
      in 1 case and a single mass in 3 cases. Sixteen patients had stenosis of the bile
      duct at the hilar hepatic lesion and/or the intrahepatic duct. Only 7 patients
      had typical AIP findings. Six patients were misdiagnosed with pancreatic cancer
      and 2 with bile-duct cancer. Seven cases were surgically treated. Five cases were
      misdiagnosed because of the nonexistence of, or the unfamiliarity with, the
      concept of AIP and sclerosing cholangitis with AIP. Another 3 cases were
      diagnosed with pancreatic cancer because of segmental stenosis of the main
      pancreatic duct and no or focal enlargement of the pancreas. CONCLUSIONS: The
      results of this study suggest that AIP presents a variety of imaging findings.
      The most important diagnostic factor is clinician awareness of the concept of AIP
      and the diverse nature of imaging findings.

PMID- 17185088
TI  - Autoimmune pancreatitis: more common and important than we thought?

PMID- 17185089
TI  - Third-generation cholecystectomy by natural orifices: transgastric and
      transvesical combined approach (with video).
AB  - BACKGROUND: An isolated transgastric port has some limitations in performing
      transluminal endoscopic cholecystectomy. However, transvesical access to the
      peritoneal cavity has recently been reported to be feasible and safe. OBJECTIVE:
      To assess the feasibility and the technical benefits of transgastric and
      transvesical combined approach to overcome the limitations of isolated
      transgastric ports. DESIGN: We created a transgastric and transvesical combined
      approach to perform cholecystectomy in 7 consecutive anesthetized female pigs.
      The transgastric access was achieved after perforation and dilation of the
      gastric wall with a needle knife and with a balloon, respectively. Under
      cystoscopic control, an ureteral catheter, a guidewire, and a dilator of the
      ureteral sheath were used to place a transvesical 5-mm overtube into the
      peritoneal cavity. By using a gastroscope positioned transgastrically and a
      ureteroscope positioned transvesically, we carried out cholecystectomy in all
      animals. RESULTS: Establishment of transvesical and transgastric accesses took
      place without complications. Under a carbon dioxide pneumoperitoneum controlled
      by the transvesical port, gallbladder identification, cystic duct, and artery
      exposure were easily achieved in all cases. Transvesical gallbladder grasping and
      manipulation proved to be particularly valuable to enhance gastroscope-guided
      dissection. With the exclusion of 2 cases where mild liver-surface hemorrhage and
      bile leak secondary to the sliding of cystic clips occurred, all remaining
      cholecystectomies were carried out without incidents. LIMITATIONS: Once closure
      of the gastric hole proved to be unreliable when using endoclips, the animals
      were euthanized; necropsy was performed immediately after the surgical procedure.
      CONCLUSIONS: A transgastric and transvesical combined approach is feasible, and
      it was particularly useful to perform a cholecystectomy through exclusive natural
      orifices.

PMID- 17185091
TI  - Suprapapillary puncture of the common bile duct for selective biliary access: a
      novel technique (with videos).
AB  - BACKGROUND: Selective cannulation of the bile duct while avoiding the potential
      mechanisms that initiate the cascade of pancreatic injury may prevent or minimize
      post-ERCP pancreatitis. This could be accomplished by suprapapillary needle
      puncture of the bile duct with a specially designed needle. OBJECTIVES: The aim
      of this study is to describe a new technique to perform selective biliary
      cannulation by using a novel needle-puncture device and its outcome in 28
      patients with suspected biliary pathology. DESIGN: This is a single-center,
      prospective pilot study of suprapapillary puncture of bile duct for both
      diagnosis and therapy of biliary pathology. SUBJECTS: Thirty patients were
      enrolled: 28 patients underwent suprapapillary puncture to gain biliary access,
      and 2 patients with a large periampullary diverticulum were excluded.
      INTERVENTIONS: After successful biliary cannulation by using a suprapapillary
      puncture technique and balloon dilation of the tract if necessary, stone removal,
      plastic stent insertion, and metal stent insertion were attempted. MAIN OUTCOME
      MEASUREMENTS: Successful biliary cannulation, time for cannulation, outcome of
      therapy (clearing the stones or providing stent drainage with stent insertion),
      and complications were recorded. At 60 days, the suprapapillary puncture was
      evaluated to check the status of drainage. RESULTS: Suprapapillary puncture was
      successful in 25 of the 28 patients, and, in 1 patient, it was successful after a
      week. It was useful in demonstrating a normal bile duct in 9 of 11 patients with
      suspected biliary pathology. Subsequent therapy was successful in the management
      of 11 patients with stones, benign biliary pathology in 2 patients, and malignant
      biliary pathology in 3 of 4 patients. None of the patients developed post-ERCP
      pancreatitis. Complications included small perforations that resolved with
      conservative management (n = 2), minor bleeding (n = 2), and submucosal injection
      (n = 1). At 60 days, all the puncture sites healed in patients who did not
      undergo dilation, while those with dilation of the tract had a patent orifice,
      with excellent flow of bile. CONCLUSIONS: Suprapapillary puncture for biliary
      cannulation is a useful technique for selective cannulation of the bile duct and
      avoids injury to the pancreas but with higher complication rates. Further studies
      will be needed to define its safety and its relative benefits compared with
      conventional access methods.

PMID- 17185092
TI  - Cannulation techniques for ERCP: one size does not fit all.

PMID- 17185093
TI  - Endoscopic full-thickness closure of large gastric perforations by use of tissue
      anchors.
AB  - BACKGROUND: A flexible needle-catheter tissue-anchoring device was developed to
      accomplish full-thickness tissue apposition of the GI wall. The aim of this study
      was to identify the performance of this device for repair of large iatrogenic
      gastric perforations in a porcine model. OBJECTIVES: Six pigs. DESIGN: Short-term
      survival animal study. SETTINGS: Pigs were studied while they were under general
      anesthesia. Device performance in differing gastric locations and wall
      thicknesses was assessed by 2 perforations more than 2 cm in size created for
      each pig along the greater curvature and the anterior wall. INTERVENTIONS: Each
      perforation was closed by parallel placement of tissue anchor sets sequentially
      along the length of the perforation. MAIN OUTCOME MEASUREMENTS: One week follow
      up endoscopy and necropsy were performed. RESULTS: Twelve perforations were
      closed with the 48 tissue anchor sets. All animals survived for 1 week without
      clinical complications. Follow-up endoscopy and necropsy revealed that all tissue
      anchors remained with firmly held sutures and sealed perforations. CONCLUSIONS:
      Full-thickness closure with a new tissue-anchoring device simply and successfully
      repaired large iatrogenic gastric perforations.

PMID- 17185094
TI  - A novel retrograde-viewing auxiliary imaging device (Third Eye Retroscope)
      improves the detection of simulated polyps in anatomic models of the colon.
AB  - BACKGROUND: Colonoscopy is the "gold standard" for colorectal polyp and cancer
      detection, but important lesions may be missed on the proximal aspect of haustral
      folds, rectal valves, or flexures. OBJECTIVE: Our purpose was to evaluate a
      prototype auxiliary imaging device that extends beyond the colonoscope's tip,
      providing a continuous retrograde view to detect lesions missed by the forward
      viewing colonoscope. DESIGN: Three anatomic models of the colon were prepared
      with simulated polyps, 32% in obvious locations and 68% on the proximal aspect of
      folds. Six endoscopists examined each model with two methods. Method A used a
      standard video colonoscope. Method B involved an identical colonoscope with a
      retrograde-viewing auxiliary device positioned within its instrument channel.
      Order of testing was randomized and blinded. SETTING: Laboratory bench. MAIN
      OUTCOME MEASUREMENTS: Detection rates for simulated polyps. RESULTS: Of 78
      "obvious" polyps, 69 (88%) and 70 (90%) were detected by methods A and B,
      respectively (P > .9). In contrast, of 162 polyps on proximal aspects of folds,
      20 (12%) and 131 (81%) were detected by methods A and B, respectively (P <
      .00001). LIMITATIONS: Limitations resulted from (1) use of commercially available
      anatomic models in which haustral folds are less prominent and more rigid than in
      humans and (2) evaluation of a prototype device that had larger size and narrower
      angle of view than the planned production model and that was fixed in relation to
      the colonoscope. CONCLUSIONS: In simulated testing, a retrograde-viewing
      auxiliary imaging device used with a standard video colonoscope significantly
      improves detection rates of simulated polyps and promises to enhance the
      diagnostic yield of colonoscopy in humans.

PMID- 17185096
TI  - Blue rubber bleb nevus syndrome: capsule endoscopy in a patient with GI bleeding.

PMID- 17185095
TI  - Who is the best colonoscopist?

PMID- 17185097
TI  - Dorsal agenesis of pancreas: CT and ERCP.

PMID- 17185098
TI  - Diagnosis of lymphoma in overt obscure GI bleeding aided by capsule endoscopy.

PMID- 17185100
TI  - Narrow band imaging directed EMR for Barrett's esophagus with high-grade
      dysplasia.

PMID- 17185099
TI  - A case of colonic morule with colitis cystica profunda.

PMID- 17185101
TI  - Ingested foreign-body retrieval: a novel new method.

PMID- 17185102
TI  - Laparoscopic observation of 2 cases of nodular regenerative hyperplasia of the
      liver.

PMID- 17185103
TI  - Portobiliary fistula at ERCP.

PMID- 17185104
TI  - Acute pancreatitis and cholangitis caused by hemobilia from biliary
      papillomatosis.

PMID- 17185105
TI  - The esophagogastric junction can only be assessed by histologic examination.

PMID- 17185107
TI  - Prophylactic clip application should be the standard of care to prevent
      postpolypectomy bleeding.

PMID- 17185108
TI  - Endoscopy-assisted wireless intragastric pH monitoring.

PMID- 17185109
TI  - Prophylactic clip application after colonic polypectomy.

PMID- 17185111
TI  - Contribution of systolic and diastolic abnormalities to heart failure with a
      normal and a reduced ejection fraction.
AB  - Heart failure (HF) has traditionally been divided into HF with a reduced ejection
      fraction (EF; systolic HF) and HF with a normal EF (diastolic HF). Both groups
      have reductions in exercise tolerance, neurohumoral activation, and abnormal left
      ventricular (LV) filling dynamics and impaired relaxation. Although the normal EF
      indicates that pump performance is adequately compensated, some of the patients
      with HF and a normal EF have reduced longitudinal systolic velocity indicating
      cardiac muscular contractile dysfunction. Regardless of EF, the severity of HF
      and its prognosis and degree of exercise intolerance are closely related to the
      degree of diastolic filling abnormalities. Patients with HF and a reduced EF have
      ventricular dilatation and elongated myocytes, whereas patients with HF and a
      normal EF do not. Thus, patients with HF have diastolic abnormalities regardless
      of EF and many patients with HF and a normal EF have contractile abnormalities
      despite preserved systolic pump performance. Heart failure with a normal EF and a
      reduced EF differs in the systolic LV pump performance and the type of
      remodeling. The mechanism of the differing remodeling responses is not known, but
      aging, sex differences, and diabetes may contribute.

PMID- 17185112
TI  - Role of gender in heart failure with normal left ventricular ejection fraction.
AB  - Heart failure with normal ejection fraction (HF-NEF) is frequently believed to be
      more common in women than in men. However, the interaction of gender and age has
      rarely been analyzed in detail, and knowledge of the distinction between pre- and
      postmenopausal women is lacking. Some of the studies that have described a higher
      prevalence of HF-NEF in women relied on clinical diagnoses of HF together with
      normal systolic function and did not measure diastolic function. This applies to
      the analysis of patients hospitalized for HF and some epidemiological
      investigations that agree on the greater prevalence of HF-NEF in women.
      Population-based studies with echocardiographic determination of diastolic
      function have suggested equal or greater prevalence of diastolic dysfunction in
      men. Major risk factors for HF-NEF include hypertension, aging, obesity,
      diabetes, and ischemia. Hypertension is more frequent in women and can contribute
      to left ventricular and arterial stiffening in a gender-specific way. Aging,
      obesity, and diabetes affect myocardial and vascular stiffness differently and
      lead to different forms of myocardial hypertrophy in women and men. In contrast,
      ischemia may play a greater role in men. Gender differences in ventricular
      diastolic distensibility, in vascular stiffness and ventricular/vascular
      coupling, in skeletal muscle adaptation to HF, and in the perception of symptoms
      may contribute to a greater rate of HF-NEF in women. The underlying molecular
      mechanisms include gender differences in calcium handling, in the NO system, and
      in natriuretic peptides. Estrogen affects collagen synthesis and degradation and
      inhibits the renin-angiotensin system. Effects of estrogen may provide benefit to
      premenopausal women, and the loss of its protective mechanisms may render the
      heart of postmenopausal women more vulnerable. Thus, a number of molecular
      mechanisms can contribute to the gender differences in HF-NEF.

PMID- 17185113
TI  - Ventricular-arterial and ventricular-ventricular interactions and their relevance
      to diastolic filling.
AB  - Chronic heart failure is a common clinical problem, and, until recently,
      attention has focused predominantly on those patients with reduced left
      ventricular (LV) systolic function, as evidenced by a reduced LV ejection
      fraction. However, nearly half of all patients thought clinically to have heart
      failure have a "preserved" LV ejection fraction, variously defined as greater
      than 40% to 45% ("heart failure with normal ejection fraction" syndrome). The
      interaction of the heart with the systemic vasculature, termed ventricular
      arterial coupling, is a key determinant of cardiovascular performance. The
      capacity of the body to augment cardiac output, regulate systemic blood pressure,
      and respond appropriately to elevations in heart rate and preload depends on both
      the properties of the heart and the properties of the vasculature into which the
      heart ejects blood. Although the marked increase of arterial and cardiac
      stiffness with aging can maintain ventricular-vascular coupling within a normal
      range, it does have detrimental effects on hemodynamic stability and cardiac
      reserve. Patients with heart failure with normal ejection fraction have been
      shown to have both arterial and ventricular stiffening, resulting in enhanced
      pressure-load dependence and sensitivity of blood pressure to circulating volume
      and diuretics. There is also indirect evidence to suggest that on exercise,
      increased external constraint to LV filling (as a result of diastolic ventricular
      interaction and pericardial constraint) may contribute to impaired use of the
      Starling mechanism in this group of patients.

PMID- 17185114
TI  - Role of exercise and metabolism in heart failure with normal ejection fraction.
AB  - Left ventricular dysfunction associated with metabolic disorders has a number of
      features that might shed light on the integrity of heart failure with normal
      ejection fraction. First, although these patients may be dyspneic and have a
      normal ejection fraction, their diastolic dysfunction is not isolated. Both
      experimental models and sensitive new parameters in humans have shown abnormal
      systolic function, even though the less sensitive parameters (such as ejection
      fraction) become abnormal only with stress. Moreover, the mechanistic
      contributors to myocardial dysfunction, including structural changes and
      metabolic influences on the cardiac myocyte, interstitial fibrosis, vascular
      disease, and altered loading, are likely to influence systolic as much as
      diastolic function. The responses of systolic and diastolic heart failure to
      exercise training show analogies, particularly with respect to the importance of
      peripheral adaptation, as well as a similar training response. Together, these
      features are more supportive of a continuum of pathophysiology between systolic
      and diastolic heart failure, rather than the 2 representing discreet phenomena.

PMID- 17185115
TI  - Diastolic heart failure: a separate disease or selection bias?
AB  - Chronic heart failure (CHF) is often subdivided based on left ventricular
      ejection fraction (LVEF) in 2 distinct forms, usually specified as "diastolic
      heart failure" and "systolic heart failure." In this review, arguments are
      provided against an LVEF-based bimodal view, and CHF is presented as one
      pathophysiological identity encompassing a continuous spectrum of closely related
      phenotypes. Most importantly, there is currently no pathophysiological basis to
      support a bimodal view. As a result, conceptual presentations of CHF, such as the
      vicious circle paradigm of CHF, become obsolete. Furthermore, the binary view of
      CHF is the unfortunate result of selection biases that has confounded practically
      all clinical trials of CHF. Unfortunately, current investigations still introduce
      selection bias when studying heart failure at preserved or reduced LVEF. Future
      investigations should analyze CHF as one disease and focus on the mechanisms
      through which disease modifiers such as sex, diabetes, and hypertension induce
      phenotypic diversity.

PMID- 17185116
TI  - Making sense of noninferiority: a clinical and statistical perspective on its
      application to cardiovascular clinical trials.
AB  - Active control noninferiority trials are being used with increasing frequency in
      new drug or device development when standard placebo-controlled trials are
      considered unethical. Nevertheless, the design and analysis of these trials are
      founded on a number of assumptions and arbitrary criteria that are generally not
      well understood or justifiable. Trials designed to show noninferiority require an
      appropriate reference population, a proven active control and dose, an
      appropriate margin of noninferiority that is clinically relevant and
      statistically justifiable, a high level of adherence to treatment, and adequate
      statistical power to reliably conclude that a treatment is truly noninferior and
      therefore effective. Accordingly, if noninferiority trials are to be applied to
      clinical and regulatory decisions regarding the marketing and use of new
      treatments, the assumptions must be made explicit and their influence on the
      resultant conclusions must be assessed rigorously. When conservative criteria
      were applied to each of the key assumptions underlying 2 representative
      noninferiority trials, they materially undermined the conclusions regarding
      noninferiority failing to confirm reported conclusions regarding noninferiority
      despite enthusiastic dissemination and acceptance of the results. Because the
      clinical, regulatory, and economic impact of active control noninferiority trials
      is substantial, robust criteria should be used routinely in their design,
      analysis, and interpretation to reach their intended objectives and to keep them
      from becoming wasted efforts.

PMID- 17185117
TI  - Digital and advanced imaging in endodontics: a review.
AB  - This review provides an overview of digital radiography as it exists, including
      advanced imaging such as computed tomography (CT), cone beam volumetric imaging,
      and micro-CT as relevant to the practice of endodontics. An evidence-based
      approach to adoption of different imaging technologies is included to assist the
      practitioner with the selection process of imaging modalities. Commonly used
      imaging terminology is introduced, as well as the advantages and disadvantages of
      image processing. New image reconstruction techniques have been introduced that
      provide information three-dimensionally to the clinician for routine endodontic
      and surgical treatment planning. The age of three-dimensional imaging and image
      processing is here. Limitations and advantages of newly introduced imaging
      modalities are discussed briefly.

PMID- 17185118
TI  - Anesthetic efficacy of lidocaine/meperidine for inferior alveolar nerve blocks in
      patients with irreversible pulpitis.
AB  - The purpose of this prospective, randomized, single-blind study was to compare
      the anesthetic efficacy of lidocaine with epinephrine to lidocaine plus
      meperidine with epinephrine for inferior alveolar nerve blocks (IAN) in patients
      with mandibular posterior teeth experiencing irreversible pulpitis. Forty-eight
      emergency patients diagnosed with irreversible pulpitis of a mandibular posterior
      tooth randomly received, in a single-blind manner, 36 mg of lidocaine with 18 mug
      epinephrine or 36 mg of lidocaine with 18 mug of epinephrine plus 36 mg
      meperidine with 18 mug epinephrine, using a conventional inferior alveolar nerve
      block. Endodontic access was begun 15 minutes after solution deposition, and all
      patients were required to have profound lip numbness. Success was defined as no
      or mild pain (visual analog scale recordings) upon endodontic access or initial
      instrumentation. The success rate for the inferior alveolar nerve block using the
      lidocaine solution was 26%, and for the lidocaine/meperidine solution, the
      success rate was 12%. There was no significant difference (p = 0.28) between the
      two solutions. In conclusion, for mandibular posterior teeth with irreversible
      pulpitis, the addition of 36 mg of meperidine to a lidocaine solution
      administered in a conventional IAN block did not improve the success rate over a
      standard lidocaine solution.

PMID- 17185119
TI  - The effect of preoperative acetaminophen or a combination of acetaminophen and
      Ibuprofen on the success of inferior alveolar nerve block for teeth with
      irreversible pulpitis.
AB  - This study compared preoperative administration of acetaminophen or a combination
      of acetaminophen and ibuprofen versus placebo for potential increased
      effectiveness of inferior alveolar nerve (IAN) block anesthesia. There were 40
      patients with irreversible pulpitis randomly assigned to a drug or placebo group.
      Thirty minutes after ingestion of medication, an IAN block was administered. A
      cold test was done 15 minutes after the block, and if the patients had no
      sensitivity, endodontic therapy was initiated. If the patient had no pain on
      access, the IAN was recorded as successful. If the patient had sensitivity to
      cold or to the access procedure, it was recorded as a failure. Overall success
      was 60% for all three groups. Success was 71.4% for the acetaminophen group,
      75.9% for the acetaminophen and ibuprofen group, and 46.2% for the placebo group.
      There was no significant difference between the groups; however, there was a
      trend toward higher success in the medication groups.

PMID- 17185120
TI  - The effect of operator experience in locating additional canals in maxillary
      molars.
AB  - The purpose of this study was to determine the influence of operator experience
      on the ability to locate and fill extra canals in maxillary first and second
      molars in vivo. The number of canals located and filled from maxillary first and
      second molars was recorded from three endodontic residents during the first 6
      months of their training, and then compared to the last 6 months of their
      training in a 2-yr endodontic residency program. Data from each resident was
      collected and compiled together. The study showed a statistically greater
      percentage of additional canals located and filled by residents in their last 6
      months, as compared to the same residents in their first 6 months in maxillary
      first and second molars (p < 0.05). Therefore, operator experience was found to
      improve the ability to locate and fill additional canals in maxillary first and
      second molars.

PMID- 17185121
TI  - Co-expression of cyclooxygenase-2 and vascular endothelial growth factor in
      inflamed human pulp: an immunohistochemical study.
AB  - Recent data from the medical literature indicates that cyclooxygenase-2 (COX-2)
      plays a key role in the production of vascular endothelial growth factor (VEGF),
      a glycoprotein that has the ability to increase the permeability of blood vessels
      and to induce angiogenesis. This study was undertaken to investigate the
      immunohistological co-expression of COX-2 and VEGF in inflamed human pulp, in
      conjunction with the expression of CD34, a transmembrane glycoprotein expressed
      in endothelial cells. Pulp tissue of extracted carious human third molars with a
      recent history of spontaneous pain were collected and processed for
      immunostaining of COX-2, VEGF, and CD34 using the biotin-streptoavidin method.
      Healthy pulp samples served as controls. COX-2 expression was not observed in
      healthy pulps, whereas all inflamed pulps demonstrated COX-2-expressing cells.
      Similarly, VEGF was not expressed in normal pulp tissue, but was strongly
      positive in inflamed pulps. CD34 was expressed in the endothelium of both normal
      and inflamed pulp tissues. Co-expression of COX-2 and VEGF in all consecutive
      sections of inflamed pulps could be suggestive of a possible release of VEGF via
      a COX-2-dependent pathway.

PMID- 17185122
TI  - The role of apical size determination and enlargement in the reduction of
      intracanal bacteria.
AB  - The master apical preparation size in root canal therapy is debatable despite
      considerable research. The present study compared file sizes that bind at the
      apex before and during crown-down preparation and assessed the relation between
      apical size and extent of intracanal bacterial load. There were 100 single-rooted
      teeth biomechanically prepared after inoculation with Enterococcus faecalis.
      Canals were preflared, and apical size was ascertained by the first file to bind
      (FAB) at the working length (WL). During crown-down preparation, the first crown
      down file to reach the apex during instrumentation was noted (CDF). Teeth were
      then divided into three master apical file size groups of CDF + 1, CDF + 2, and
      CDF + 3. Positive controls were inoculated postinstrumentation, whereas negative
      controls were instrumented without inoculation (n = 5). The samples were then
      cultured for intracanal bacterial counts. Fifteen samples and four controls were
      analyzed under SEM. The data were analyzed using ANOVA, Student's t-test, and
      chi(2) tests. The CDF was demonstrated to be an average of four file sizes larger
      than the FAB (p < 0.05). There was a significant increase in the number of
      samples with negative cultures from CDF + 1 to CDF + 3. SEM observation revealed
      bacteria on dentinal walls and in tubules even in most negative canal cultures.

PMID- 17185123
TI  - Short-term cytotoxicity assessment of components of the epiphany resin-percha
      obturating system by indirect and direct contact millipore filter assays.
AB  - The Epiphany Resin-Percha Obturating System was assessed for cytotoxicity,
      compared with gutta-percha and AH-Plus sealer. Specimen disks (Resilon, gutta
      percha), filled glass rings (sealers), or imbibed cellulose disks (primer,
      thinning resin) were placed over Millipore filters in direct or indirect contact
      with HeLa cell monolayer, incubated for 2 hours, and stained with tetrazolium
      blue. Cytotoxicity was rated by the surrounding unstained zone: none (0 mm), mild
      (</=7 mm), moderate (7-12 mm), or marked (>12 mm). Data were analyzed with one
      way ANOVA and post hoc pairwise t tests. Unstained zones indicating moderate
      cytotoxicity were significantly larger (p < 0.05) for Epiphany primer than for
      thinning resin and for freshly mixed AH-Plus than for Epiphany sealer. Set
      sealers (24 and 48 hours), gutta-percha, and Resilon elicited noncytotoxic
      responses. In conclusion, cytotoxicity of set Epiphany sealer and Resilon was
      comparable with that of set AH-Plus and gutta-percha. Cytotoxicity of freshly
      mixed Epiphany sealer, primer, and thinning resin did not exceed that of freshly
      mixed AH-Plus.

PMID- 17185124
TI  - The antimicrobial effect of MTAD, sodium hypochlorite, doxycycline, and citric
      acid on Enterococcus faecalis.
AB  - This study compared the antimicrobial effect of MTAD, two of its components,
      doxycycline and citric acid, and sodium hypochlorite (NaOCl) in two in vitro
      models on Enterococcus faecalis. In the bovine tooth model, the lumens of 30
      bovine dentin discs were infected with E. faecalis for 2 weeks before treating
      with either one of the experimental irrigants or saline. Bacteria in the shavings
      were collected with two sizes of burs and enumerated after overnight culturing.
      Zones of inhibition were recorded in the agar diffusion model for each irrigant.
      In the tooth model, NaOCl and doxycycline were more effective than control in
      killing E. faecalis at the shallow bur depth, but at the deeper bur depth only
      NaOCl was superior. In the agar diffusion model, NaOCl produced less inhibition
      than MTAD or doxycycline.

PMID- 17185125
TI  - Influence of moisture on the apical seal of root canal fillings with five
      different types of sealer.
AB  - The aim of this study was to evaluate the influence of moisture on apical leakage
      using five different types of sealer. There were 120 single-rooted teeth
      instrumented to .02/#60 and randomly assigned to 10 experimental groups, one
      control group (AH Plus, lateral condensation) (n = 10) or positive/negative
      controls (n = 5). Before obturation teeth were dried thoroughly, followed by
      recontamination with moisture in a wet chamber (moist groups; 37 degrees C for 7
      days). The teeth of the experimental groups (a, dry; b, moist) were obturated
      with sealer (groups 1, AH Plus; 2, Apexit; 3, Ketac-Endo; 4, RoekoSeal; 5, Tubli
      Seal) and a single gutta-percha cone .02/#55. Teeth were centrifuged (30 x g for
      3 minutes) in 5% methylene blue. Linear dye penetration was measured under a
      stereomicroscope. Moisture led to less microleakage for Apexit, RoekoSeal, and
      Tubli-Seal and higher values for AH Plus and Ketac-Endo. Multifactorial ANOVA
      displayed a significant dependence of leakage on sealer (p < 0.001) and the
      combination sealer or moisture (p < 0.01). It depends on the sealer type in which
      way moisture affects the apical seal.

PMID- 17185126
TI  - Separate whitening effects on enamel and dentin after fourteen days.
AB  - The purpose of this study was to investigate the mechanism of action of a
      bleaching agent, as it relates to enamel and dentin. Twenty-six extracted human
      molar teeth were sectioned at the cemento-enamel junction and were randomly
      assigned to two groups. L*a*b* readings were taken with a spectrophotometer: on
      buccal surfaces of the crown, at enamel and dentin. The teeth were exposed to
      carbamide peroxide or placebo gel and L*a*b* scores were again recorded to
      determine color changes. Treatments were compared using ancova test with baseline
      color as the covariate. Relative to placebo, buccal surfaces exhibited the
      greatest Deltab* and DeltaL* color change. On buccal surfaces, the adjusted mean
      (SE) treatment differences were -7.8 (1.00) for Deltab* and 5.7 (0.97) for
      DeltaL, with groups differing significantly (p < 0.0001). On enamel surfaces,
      treatment differences were -3.6 (0.61) for Deltab* and 4.6 (0.80) for DeltaL* (p
      < 0.0001). Dentin exhibited the least color improvement. Adjusted mean (SE)
      treatment differences were -1.9 (0.87) for Deltab* and 2.4 (1.10) for DeltaL*,
      with groups differing significantly (p < 0.02) on dentin color change. The
      majority of color change seen on the buccal surface of tooth crowns exposed to
      carbamide peroxide 15% was because of the color change in enamel. As compared to
      enamel, dentin was less affected after 14 days.

PMID- 17185127
TI  - Efficacy of two rotary NiTi instruments in the removal of Gutta-Percha during
      root canal retreatment.
AB  - The aim of this study was to evaluate the efficacy of ProTaper and K3 in the
      removal of gutta-percha during root canal retreatment in comparison with hand
      Hedstrom files. Time of gutta-percha removal and amount of apically extruded
      debris were also evaluated. Sixty extracted single-rooted anterior teeth and
      premolars were instrumented and obturated with laterally condensed gutta-percha
      technique. The teeth were cleared and randomly divided into three groups of 20
      teeth each. The roots were split longitudinally, digital images were created
      using a scanner, and the areas of remaining filling material were traced using
      Ulead Photoimpact7 then calculated using SigmaScan software. The results
      indicated that the two rotary nickel-titanium instruments left significantly less
      remaining filling material than hand instruments (p < 0.001). The ProTaper and K3
      required significantly less time for filling material removal than hand
      instruments (p < 0.001). There was no statistically significant difference among
      the three techniques regarding the amount of apically extruded debris (p =
      0.159). In conclusion, ProTaper and K3 were found to be effective and faster in
      removing gutta-percha.

PMID- 17185128
TI  - Comparison of 5.25% sodium hypochlorite, MTAD, and 2% chlorhexidine in the rapid
      disinfection of polycaprolactone-based root canal filling material.
AB  - The purpose of this investigation was to compare the effectiveness of 5.25%
      sodium hypochlorite, MTAD, and 2% chlorhexidine in the rapid disinfection of
      Resilon pellets. Resilon pellets were randomly selected, contaminated with
      Enterococcus faecalis, and disinfected with 5.25% sodium hypochlorite, MTAD, or
      2% chlorhexidine. Positive and negative controls were used. All samples were air
      dried, washed in sterile water, placed in centrifuge tubes containing BHI broth,
      and incubated at 37 degrees C for up to 7 days. Broths were visually checked for
      turbidity and scored for growth. Samples from each experimental and control group
      were randomly chosen, plated, incubated at 37 degrees C, and checked visually for
      growth. If growth occurred, a gram stain was performed to identify bacterial
      species. Results indicate that 5.25% sodium hypochlorite, MTAD, and 2%
      chlorhexidine were all effective in the rapid disinfection of Resilon and gutta
      percha pellets, and a 1-minute immersion was sufficient to disinfect.

PMID- 17185129
TI  - Enterococcus faecalis type strain leakage through root canals filled with Gutta
      Percha/AH plus or Resilon/Epiphany.
AB  - The aim of this in vitro study was to compare leakage of Enterococcus faecalis
      ATCC 29212 through root canals of single-rooted extracted human mandibular
      premolars filled with either gutta-percha/AH Plus or Resilon/Epiphany using the
      continuous wave of condensation technique. Test and control teeth were suspended
      in an experimental bacterial leakage setup for 50 days. Kaplan-Meyer curves
      showed a tendency of the gutta-percha/AH Plus root fillings to prevent leakage
      better than Resilon/Epiphany counterparts. This tendency, however, was not
      statistically significant (log-rank test, p = 0.141). The estimated mean time for
      turbidity to occur in the broth below the suspended root was 35 days (SD = 5
      days) in the gutta-percha/AH Plus and 33 days (SD = 4 days) in the
      Resilon/Epiphany group. It was concluded that within the limitations of this
      study, there was no apparent advantage of using Resilon/Epiphany over gutta
      percha/AH Plus.

PMID- 17185130
TI  - Comparison of the antimicrobial efficacy of 1.3% NaOCl/BioPure MTAD to 5.25%
      NaOCl/15% EDTA for root canal irrigation.
AB  - The purpose of this study was to compare the antimicrobial efficacy of 1.3%
      NaOCl/BioPure MTAD to 5.25% NaOCl/15% EDTA for root canal irrigation. Twenty-six
      bilaterally matched pairs of human teeth were collected. The teeth were incubated
      with Enterococcus faecalis for 4 weeks. The teeth were divided into two
      experimental groups and one positive control group. The canals were instrumented
      and irrigated with either 5.25% NaOCl/15% EDTA or 1.3% NaOCl/BioPure MTAD.
      Bacterial samples were collected after instrumentation/irrigation and after
      additional canal enlargement. Statistical analysis of the data using the Wilcoxon
      Signed Rank test showed significant differences between the experimental groups.
      The first bacterial samples revealed growth in 0 of 20 samples with 5.25%
      NaOCl/15% EDTA irrigation and in 8 of 20 samples with 1.3% NaOCl/BioPure MTAD
      irrigation. Samples taken after additional canal enlargement revealed growth in 0
      of 20 samples in 5.25% NaOCl/15% EDTA and in 10 of 20 samples in 1.3%
      NaOCl/BioPure MTAD group. This investigation showed consistent disinfection of
      infected root canals with 5.25% NaOCl/15% EDTA. The combination of 1.3%
      NaOCl/BioPure MTAD left nearly 50% of the canals contaminated with E. faecalis.

PMID- 17185131
TI  - The effect of operational speed on the fracture of nickel-titanium rotary
      instruments.
AB  - The purpose of this study was to compare the number of rotations to fracture of
      nickel-titanium (NiTi) rotary files operated at different speeds and different
      angles. We used 60 Profile NiTi rotary files, size 25 (30 each of 0.04 and 0.06
      taper), operated at speeds of 350 or 600 rpm at angles of 25, 28, and 33.5
      degrees. The time to fracture and number of rotations to fracture were recorded
      and calculated. A significant (p < 0.001) difference was found in the number of
      rotations to fracture according to taper and angle. Files of 0.06 taper fractured
      more readily than files of 0.04 taper. Increasing the angle at which the file was
      rotated decreased the number of rotations to fracture for both tapers; 0.04-taper
      files were more affected by an increase in the angle than the 0.06-taper files.
      However, the number of rotations to fracture was not related to the speed at
      which the files were operated.

PMID- 17185132
TI  - Cyclic fatigue of ProTaper instruments.
AB  - The present work evaluated the influence of the curved segment length of
      artificial root canals (the arc) and the number of cycles necessary to fracture
      engine-driven nickel-titanium endodontic instruments. ProTaper F3 25-mm files at
      250 rpm were used in two artificial canals. The artificial canals were made of
      stainless steel with an inner diameter of 1.04 mm, a total length of 20 mm, and
      arc on the ends with a radius of curvature of 6 mm. The arc length of the first
      tube measured 9.4 mm, and the straight part measured 10.6 mm. The second tube was
      14.1 mm long, and the straight part measured 5.9 mm. We determined the fracture
      surface distances and the number of cycles necessary to induce fatigue fracture
      in the ProTaper F3 instruments. The fracture surfaces and the helical shaft of
      the instruments were investigated using a scanning electron microscope. The
      results indicated that the required number of cycles to cause a fracture was
      influenced by the canal arc length, the morphology of the fractured surface
      presented ductile characteristics, and plastic deformation in the helical shaft
      of the fractured instruments did not occur.

PMID- 17185133
TI  - The radix entomolaris and paramolaris: clinical approach in endodontics.
AB  - Mandibular molars can have an additional root located lingually (the radix
      entomolaris) or buccally (the radix paramolaris). If present, an awareness and
      understanding of this unusual root and its root canal morphology can contribute
      to the successful outcome of root canal treatment. This report discusses
      endodontic treatment of three mandibular molars with a radix entomolaris or
      paramolaris, both of which are rare macrostructures in the Caucasian population.
      The prevalence, the external morphological variations and internal anatomy of the
      radix entomolaris and paramolaris are described. Avoiding procedural errors
      during endodontic therapy demand an adapted clinical approach to diagnosis and
      root canal treatment.

PMID- 17185134
TI  - Unusual variant of type 3 dens invaginatus in a maxillary canine: a rare case
      report.
AB  - A 13-year-old boy presented with clinical symptoms of periapical inflammation
      related to the right maxillary canine. A bizarre radiographic appearance of the
      root was considered suggestive of a compound odontome. Histological examination
      of the surgically extracted canine revealed a very rare variant of Oehlers' type
      3 invagination. The invagination originated in a pit above the cingulum as a
      narrow coronal channel that opened into a large cavity inside the dilated root.
      The radicular part of the invagination contained all components of the attachment
      apparatus. The root canal and its apical foramen were slit-like and circular.
      Radiographic appearance of two roots separated by a wide interradicular area in a
      normally single-rooted tooth is indicative of this variant of type 3
      invagination. Timely prophylactic treatment and follow-up or early endodontic
      treatment confined to the coronal channel are crucial to prevent pulp necrosis
      and consequent loss of the tooth.

PMID- 17185136
TI  - Hemoperfusion as an effective alternative therapy for star fruit intoxication: a
      report of 2 cases.
AB  - This report describes 2 cases of star fruit intoxication successfully treated
      with charcoal hemoperfusion (CHP). Common clinical characteristics of the
      reported cases included persistent hiccup, consciousness disturbance, coma, need
      for ventilator support, and admission to an intensive care unit. The optimum
      treatment for star fruit intoxication has been controversial, with modality,
      dose, and appropriate timing of extracorporeal therapy debated. Analysis of the 2
      reported cases shows several advantages of CHP, including increased extraction
      efficiency, rapid recovery of consciousness, decreased time of intensive care
      unit admission, and good clinical tolerance. CHP may provide an alternative
      treatment modality in cases with life-threatening star fruit intoxication with
      poor response to intensified hemodialysis.

PMID- 17185135
TI  - Expression and distribution of notch protein members in human placenta throughout
      pregnancy.
AB  - Notch signaling is an evolutionarily conserved mechanism used by invertebrates
      and vertebrates to control cell fates through close-range cell interactions. Four
      Notch receptors have been identified in vertebrates and different ligands,
      divided into Delta-like and Serrate-like (Jagged). Several studies have
      demonstrated that Notch signaling is involved in different branches of the cell
      fate decision tree: differentiation, proliferation and apoptosis. These three
      processes are finely regulated in human placenta in order to allow a successful
      pregnancy and a correct fetal growth. Moreover, Notch and its ligands participate
      in the vascular remodelling and stabilization, other two processes much important
      and ticklish in human placenta. So, we decided to investigate the pattern of
      expression of Notch-1, Notch-4 and Jagged-1, together with two members related to
      Notch pathway and involved in angiogenesis: VEGF and p21, in human placenta
      during gestation by immunoblotting and immunohistochemistry. We showed a
      modulation of Notch proteins throughout the pregnancy; in particular we showed a
      slight decrease of Notch-1 throughout pregnancy, with a decreased cytoplasmic
      staining from the first to the third trimester of gestation in cytotrophoblast
      and syncytiotrophoblast. In contrast Jagged-1 showed an increase throughout
      pregnancy especially in syncytiotrophoblast and stroma during the third trimester
      of gestation. In addition, we found by immunoblotting an increase of VEGF
      expression from the first to the third trimester and an intense VEGF expression
      inside endothelial cells throughout the gestation as also confirmed by
      immunohistochemistry. We also showed a decrease of p21 expression during the
      pregnancy both through immunoblotting and immunohistochemistry assays. Moreover,
      we observed Notch localization in extravillous trophoblast cells that are able to
      invade the decidualized endometrium. Our results suggest an involvement of Notch
      signaling in regulation of placental cell fate decision and in angiogenesis that
      are dramatically important to maintain a normal physiology of this organ during
      pregnancy.

PMID- 17185137
TI  - Gross genomic rearrangement involving the TSC2-PKD1 contiguous deletion syndrome:
      characterization of the deletion event by quantitative polymerase chain reaction
      deletion assay.
AB  - Tuberous sclerosis complex (TSC) was instrumented for identification of the gene
      causing autosomal dominant polycystic kidney disease type 1 (PKD1) because a
      patient showing both diseases gave rise to the suggestion that the TSC2 gene is
      located in close vicinity on chromosome 16p13. However, distinct molecular
      genetic characterization of such patients is sparse in the literature. A 41-year
      old woman was admitted because of chylous ascites and pleural effusions. She was
      on hemodialysis therapy for 6 years because of end-stage renal failure from PKD.
      Both kidneys had been removed at ages 35 and 36 years. Histologically, both
      specimens also showed multiple angioleiomyolipoma. Mild, but classic, lesions of
      the TSC complex were present on her face and hands and in the central nervous
      system. The genetic defect was identified by using quantitative real-time
      polymerase chain reaction (qPCR), long-range PCR (LR-PCR), and sequencing. qPCR
      confirmed the existence of a TSC2-PKD1 contiguous gene deletion spanning the
      entire TSC2 and PKD1 genes. Additional analysis showed expansion of the deletion
      affecting the adjacent downstream-located genes RAB26 and TRAF7, as well as the
      great majority of CASKIN1. LR-PCR and sequencing identified flanking simple
      tandem repeats. A nonhomologous misalignment mechanism has driven the
      recombination, most likely by replication slippage between a 3-bp homology (ATG)
      at the breakpoint regions. Our results confirm that patients with both TSC and
      PKD have a genetically contiguous gene syndrome with hemizygous deletion of the
      TSC2 and PKD1 genes. Despite this maximal genetic defect, the typical signs of
      TSC, mental retardation and seizures, can be absent.

PMID- 17185138
TI  - Chronic tubulointerstitial nephritis presenting as multiple renal nodules and
      pancreatic insufficiency.
AB  - We report a case of chronic tubulointerstitial nephritis associated with multiple
      nodular lesions of the kidneys in a patient with autoimmune pancreatitis. Serum
      immunoglobulin G4 (IgG4) level was increased, and immunohistochemical staining
      for IgG4 on the renal biopsy specimen showed positive staining of plasma cells
      and tubular basement membrane within areas of chronic tubulointerstitial
      nephritis. There are a few reports of nodular lesions of kidneys or interstitial
      nephritis associated with autoimmune pancreatitis. Our case is unique in that all
      3 conditions presented together and suggests that interstitial nephritis can
      present as nodular lesions.

PMID- 17185139
TI  - The challenges of the next 5 years.

PMID- 17185140
TI  - Recommendations for reporting of clinical research studies.

PMID- 17185141
TI  - Should CKD be a coronary heart disease risk equivalent?

PMID- 17185142
TI  - Antihypertensive therapy in the presence of proteinuria.
AB  - The presence of proteinuria is a well-known risk factor for both the progression
      of renal disease and cardiovascular morbidity and mortality, and decreases in
      urine protein excretion level were associated with a slower decrease in renal
      function and decrease in risk of cardiovascular events. Increased blood pressure
      has a major role in the development of proteinuria in patients with either
      diabetic or nondiabetic kidney disease, and all recent guidelines recommend a
      blood pressure goal less than 130/80 mm Hg in patients with proteinuria to
      achieve maximal renal and cardiovascular protection. Drugs interfering with the
      renin-angiotensin system, ie, angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers, should be used as first-line antihypertensive
      therapy in patients with proteinuria because they seem to have a blood pressure
      independent antiproteinuric effect, and if blood pressure levels are still out of
      goal, a diuretic should be added to this regimen. A combination of an angiotensin
      converting enzyme inhibitor with an angiotensin receptor blocker or other classes
      of medications shown to decrease protein excretion, such as nondihydropyridine
      calcium antagonists or aldosterone receptor blockers, should be considered to
      decrease proteinuria further. This review provides an extended summary of current
      evidence regarding the associations of blood pressure with proteinuria, the
      rationale for currently recommended blood pressure goals, and the use of various
      classes of antihypertensive agents in proteinuric patients.

PMID- 17185143
TI  - The creation of an advance care planning process for patients with ESRD.
AB  - Comprehensive care of patients with end-stage renal disease (ESRD) requires
      expertise in advance care planning (ACP), including attention to ethical,
      psychosocial, and spiritual issues related to starting, continuing, withholding,
      and stopping dialysis therapy. ACP currently is under evolution from a document
      driven decision-focused event. This article describes a new approach to ACP that
      emphasizes a relational patient-centered process that focuses on broader goals of
      care for a particular dialysis patient with known medical problems and is
      designed to serve as a guide to help nephrologists, social workers, and other
      health care professionals explore ACP discussions with their patients with ESRD.
      Specifically, we define ACP, highlight goals and key features of this facilitated
      ACP process, and provide an interview guide with examples of questions that can
      be used to explore the various aspects of ACP with patients and their families.
      Outcomes of such an ACP process will not be measured by increasing the number of
      completed advance directives, but by improving satisfaction with the entire end
      of-life experience and having outcomes match patient preferences. It is expected
      that such a process will enhance shared decision making among patient, surrogate,
      and health care provider and help build strong and intimate relationships that
      can only serve to enhance end-of-life care. Throughout this process, patients are
      not abandoned as they confront the realities of declining health and functional
      status, but rather are supported through their illness and life on dialysis
      treatment.

PMID- 17185144
TI  - The impact of reclassifying moderate CKD as a coronary heart disease risk
      equivalent on the number of US adults recommended lipid-lowering treatment.
AB  - BACKGROUND: The Third National Cholesterol Education Program Adult Treatment
      Panel (ATP-III) guidelines recommend consideration of lipid-lowering therapy at
      lower low-density lipoprotein cholesterol levels (>or=100 mg/dL [>or=2.59
      mmol/L]) for adults with coronary heart disease risk equivalents. Chronic kidney
      disease is associated with increased coronary heart disease risk but is not
      included as a risk equivalent in these guidelines. METHODS: The impact of
      including moderate chronic kidney disease (estimated glomerular filtration rate,
      30 to 59 mL/min/1.73 m(2) [0.50 to 0.98 mL/s]) as a coronary heart disease risk
      equivalent on the percentage and number of US adults with chronic kidney disease
      recommended lipid-lowering therapy was estimated by using data from the Third
      National Health and Nutrition Examination Survey. RESULTS: Of adults with
      moderate chronic kidney disease, 53.0% had a history of coronary heart disease or
      a risk equivalent, 24.7% reported a history of myocardial infarction or stroke,
      17.7% had diabetes, 9.6% had angina, and 26.9% had a 10-year coronary heart
      disease risk greater than 20%. Using current ATP-III guidelines, lipid-lowering
      therapy is recommended for 61.4% of adults with moderate chronic kidney disease.
      If moderate chronic kidney disease was reclassified as a coronary heart disease
      risk equivalent, this percentage would increase to 87.7%, representing an
      increase in number of adults with moderate chronic kidney disease recommended
      lipid-lowering treatment from 4.5 to 6.5 million adults. CONCLUSION: This
      analysis shows that a majority of adults with moderate chronic kidney disease
      have coronary heart disease or risk equivalents. Nonetheless, a substantially
      greater proportion of US adults with moderate chronic kidney disease would be
      recommended lipid-lowering therapy through its reclassification as a coronary
      heart disease risk equivalent.

PMID- 17185145
TI  - Epidemiological features of CKD in Taiwan.
AB  - BACKGROUND: The incidence of end-stage renal disease (ESRD) in Taiwan is the
      highest in the world. However, epidemiological features of earlier chronic kidney
      disease (CKD) have not been investigated. METHODS: Since implementation of the
      National Health Insurance Program in 1995, more than 96% of the population in
      Taiwan has been enrolled. A nationally representative cohort of 200,000
      individuals randomly sampled from the National Health Insurance enrollees was
      followed up from 1996 to 2003. Clinical conditions were defined by using
      diagnostic codes. The prevalence and incidence of clinically recognized CKD were
      assessed. We also identified risk factors associated with the development of CKD.
      RESULTS: The prevalence of clinically recognized CKD increased from 1.99% in 1996
      to 9.83% in 2003. The overall incidence rate during 1997 to 2003 was 1.35/100
      person-years. The multivariate model indicates that age is a key predictor of
      CKD, with an odds ratio of 13.95 for the group aged 75-plus years compared with
      the group younger than 20 years. Other factors associated with increased risk for
      the development of CKD include diabetes, hypertension, hyperlipidemia, and female
      sex. CONCLUSION: The prevalence and incidence of CKD in Taiwan are relatively
      high compared with other countries. Our finding provides a reasonable explanation
      for the subsequent epidemic of ESRD in Taiwan. Further study is needed to
      identify the entire burden of CKD and the effectiveness of risk-factor
      modification.

PMID- 17185146
TI  - Beneficial impact of fenoldopam in critically ill patients with or at risk for
      acute renal failure: a meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Acute kidney injury is common in critically ill patients. Fenoldopam
      mesylate is a potent dopamine A-1 receptor agonist that increases blood flow to
      the renal cortex and outer medulla. Because there is uncertainty about the
      benefits of fenoldopam in such a setting, we performed a systematic review of
      randomized controlled trials of intensive care unit patients or those undergoing
      major surgery. METHODS: BioMedCentral, CENTRAL, PubMed, and conference
      proceedings were searched (updated October 2005). Investigators and external
      experts were contacted. Two unblinded reviewers selected randomized controlled
      trials that used fenoldopam in the prevention or treatment of acute kidney injury
      in postoperative or intensive care patients. Studies involving the prevention of
      contrast nephropathy or containing duplicate data were excluded from analysis.
      Two reviewers independently abstracted patient data, treatment characteristics,
      and outcomes. RESULTS: A total of 1,290 patients from 16 randomized studies were
      included in the analysis. Pooled estimates showed that fenoldopam consistently
      and significantly reduced the risk for acute kidney injury (odds ratio [OR],
      0.43; 95% confidence interval [CI], 0.32 to 0.59; P < 0.001), need for renal
      replacement therapy (OR, 0.54; 95% CI, 0.34 to 0.84; P = 0.007), and in-hospital
      death (OR, 0.64; 95% CI, 0.45 to 0.91; P = 0.01). These benefits were associated
      with shorter intensive care unit stay (weighted mean difference, -0.61 days; 95%
      CI, -0.99 to -0.23; P = 0.002). Sensitivity analyses, tests for small-study bias,
      and heterogeneity assessment further confirmed the main analysis. CONCLUSION:
      This analysis suggests that fenoldopam reduces the need for renal replacement and
      mortality in patients with acute kidney injury. A large, multicenter,
      appropriately powered trial will need to be performed to confirm these results.

PMID- 17185147
TI  - Multicenter study on hepatitis C virus-related cryoglobulinemic
      glomerulonephritis.
AB  - BACKGROUND: Mixed cryoglobulinemia is a multisystem disorder associated strongly
      with hepatitis C virus (HCV) infection. The kidney frequently is involved, and
      glomerulonephritis represents the key factor affecting prognosis. METHODS:
      Clinical, serological, immunogenetic, and morphological data were collected
      retrospectively from medical records of 146 patients with cryoglobulinemic
      glomerulonephritis who underwent biopsies in 25 Italian centers and 34
      cryoglobulinemic controls without renal involvement. RESULTS: Eighty-seven
      percent of patients were infected with HCV; genotype 1b was more frequent than
      genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was
      the most prevalent histological pattern (83%). Type II cryoglobulin
      (immunoglobulin Mkappa [IgMkappa]/IgG) was detected in 74.4% of cases. The
      remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox
      proportional hazard model showed that age, serum creatinine level, and
      proteinuria at the onset of renal disease were associated independently with risk
      for developing severe renal failure at follow-up. Overall survival at 10 years
      was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine
      value greater than 1.5 mg/dL (>133 mumol/L), but were unaffected by sex and HCV
      infection. Cardiovascular disease was the cause of death in more than 60% of
      patients. CONCLUSION: Data confirm the close association between mixed
      cryoglobulinemia and HCV infection and between glomerulonephritis and type II
      cryoglobulin. Survival profiles are better than previously reported in the
      literature, probably because of improvement in therapeutic regimens. Causes of
      death reflect this improvement in survival, with an increased prevalence of
      cardiovascular events compared with infectious complications and hepatic failure,
      which were predominant in the past.

PMID- 17185148
TI  - Use of do-not-resuscitate orders in patients with kidney disease hospitalized
      with acute myocardial infarction.
AB  - BACKGROUND: Patients with kidney disease are at increased risk for adverse health
      outcomes in comparison to patients without kidney disease. Therefore, patients
      with kidney disease may have greater use of do-not-resuscitate (DNR) orders than
      patients without kidney disease in the setting of an acute illness. We examined
      the association between advanced kidney disease and use of DNR orders in patients
      admitted with an acute myocardial infarction (AMI) to all greater Worcester, MA,
      hospitals as part of an epidemiological study. METHODS: Use of DNR orders in
      4,033 Worcester residents hospitalized with AMI at 11 greater Worcester medical
      centers during 1997, 1999, 2001, and 2003 was examined. Advanced kidney disease
      was defined on the basis of serum creatinine level at the time of hospital
      admission. RESULTS: Forty-nine percent of patients with kidney disease and AMI
      had a DNR order in their medical records compared with 21% of patients without
      kidney disease. After controlling for a variety of potentially confounding
      factors, patients with kidney disease were more likely to have a DNR order than
      patients without kidney disease (adjusted odds ratio, 1.55; 95% confidence
      interval, 1.21 to 1.98). Patients with advanced kidney disease who received DNR
      orders were older, had more comorbid conditions, and were at greater risk for
      dying than patients with kidney disease without a DNR order. CONCLUSION: Advanced
      kidney disease is associated with greater rates of DNR orders in patients
      hospitalized with AMI. Awareness of kidney disease may be an important
      consideration for patients and health care providers in discussing the use of DNR
      measures.

PMID- 17185149
TI  - Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term
      management and outcome.
AB  - BACKGROUND: Little information on the management and long-term follow-up of
      patients with biallelic mutations in the chloride channel gene CLCNKB is
      available. METHODS: Long-term follow-up was evaluated from 5.0 to 24 years
      (median, 14 years) after diagnosis in 13 patients with homozygous (n = 10) or
      compound heterozygous (n = 3) mutations. RESULTS: Medical treatment at last
      follow-up control included supplementation with potassium in 12 patients and
      sodium in 2 patients and medical treatment with indomethacin in 9 patients. At
      the end of follow-up, body height was 2.0 standard deviation score or less in 6
      patients; 2 of these patients had growth hormone deficiency. Body weight (<or=2.0
      standard deviation score in 6 patients) significantly increased (P < 0.05) at the
      end of follow-up in comparison to values at diagnosis. Nonpostural persistent
      proteinuria was present in 6 patients, and 4 patients had a glomerular filtration
      rate less than 75 mL/min/1.73 m(2) (<1.25 mL/s). CONCLUSION: These data show that
      some patients with biallelic mutations in the chloride channel gene CLCNKB tend
      to present with pathological proteinuria and impaired kidney function after a
      median follow-up of 14 years, and growth retardation is common and sometimes
      related to growth hormone deficiency in these patients.

PMID- 17185150
TI  - Complications, effects on dialysis dose, and survival of tunneled femoral
      dialysis catheters in acute renal failure.
AB  - BACKGROUND: Availability of a functional vascular access is a mandatory
      prerequisite for extracorporeal renal replacement therapy in patients with acute
      renal failure. The femoral site of insertion commonly is chosen because it is an
      easy and convenient access. However, an array of complications may substantially
      alter the quality of treatment, and it appears that catheter-related morbidity
      and dysfunction are more frequent with the femoral than internal jugular site.
      This study is designed to evaluate the potential benefits of using soft silicone
      tunneled catheters ((ST)Caths) at the femoral site. METHODS: Thirty patients with
      acute renal failure treated by intermittent hemodialysis (IHD) and/or continuous
      venovenous hemodiafiltration (CVVHDF) were assigned to either twin (ST)Caths or
      twin polyurethane nontunneled femoral catheters. Time necessary for catheter
      insertion, catheter-related complications, and catheter lifespan were monitored.
      Catheter performance during IHD and the effect of catheter type on dialysis dose
      were evaluated. RESULTS: The time necessary for (ST)Cath insertion was
      significantly longer. The incidence of vein thrombosis and catheter-related
      infection was lower, and the ratio of venous return pressure to catheter blood
      flow was better with an (ST)Cath. Recirculation rates were similar for both types
      of catheters. Whether treated by using IHD or CVVHDF, patients with an (ST)Cath
      benefited from a greater delivered dialysis dose. Multivariate analysis confirmed
      that (ST)Cath use was a determinant factor to optimize dialysis dose delivery.
      (ST)Cath patency was significantly longer. CONCLUSION: In patients with acute
      renal failure, use of an (ST)Cath minimizes catheter-related morbidity and
      improves dialysis efficiency compared with conventional femoral catheters.

PMID- 17185151
TI  - The effect of mesna on plasma total homocysteine concentration in hemodialysis
      patients.
AB  - BACKGROUND: Plasma total homocysteine (tHcy) level is an independent risk factor
      for the development of atherosclerosis. The degree of risk in most of the
      population is decreased by using dietary vitamin supplementation; however, more
      than 90% of patients with end-stage renal disease have increased tHcy levels
      despite supplementation. Only a small fraction of tHcy is removed by hemodialysis
      because of extensive disulfide bonding to albumin. The objective of this study is
      to determine whether a single intravenous dose of mesna, a thiol-containing drug
      analogue of taurine, facilitates tHcy clearance during hemodialysis. METHODS:
      Initial in vitro thiol exchange tests were performed with mesna in plasma from
      dialysis patients. Mesna, 300 micromol/L (49.2 mg/L), was incubated with plasma
      at 37 degrees C, and free homocysteine was measured at various times. In vivo,
      mesna activity was tested in 10 hemodialysis patients by administering 2.5 or 5.0
      mg/kg of mesna intravenously at the beginning of a treatment cycle. Blood samples
      were drawn throughout dialysis, and plasma tHcy levels were compared with those
      obtained from a previous dialysis session in which mesna was not administered.
      RESULTS: In vitro, mesna liberated 36.5% +/- 2.5% of protein-bound homocysteine
      in 30 minutes. In vivo, a single 2.5-mg/kg dose of mesna was ineffective;
      however, at 5.0 mg/kg, it caused a 55.2% +/- 3.9% decrease in plasma tHcy levels
      postdialysis compared with a 34.2% +/- 5.3% decrease with dialysis alone (P <
      0.001). CONCLUSION: Intravenous mesna causes a rapid decrease in plasma tHcy
      levels during hemodialysis.

PMID- 17185152
TI  - C-Reactive protein haplotype predicts serum C-reactive protein levels but not
      cardiovascular disease risk in a dialysis cohort.
AB  - BACKGROUND: C-Reactive protein (CRP) gene variation has been associated with
      serum CRP levels in the general population. We examined the associations of CRP
      gene variation with longitudinal CRP measurements and incident cardiovascular
      disease (CVD) risk in a cohort of 504 white and 244 African-American incident
      dialysis patients. METHODS: Seven tagging single-nucleotide polymorphisms in the
      CRP gene were selected by using the Carlson method (r(2) > 0.65). High
      sensitivity CRP was measured every 6 months (mean, 4.6 months). Haplo.glm was
      used to determine the association of haplotypes with serum CRP levels and CVD
      risk. Global tests from Haplo.score were conducted to determine statistical
      significance. RESULTS: Compared with the most common haplotype, 1 haplotype was
      associated with a 52% lower CRP level at baseline among African Americans (ratio,
      0.48; 95% confidence interval [CI], 0.28 to 0.82; global P-value = 0.0005).
      Furthermore, this haplotype was associated significantly with lower serum CRP
      levels during 36 months of follow-up. Among whites, this haplotype was associated
      with an 18% (ratio, 0.82; 95% CI, 0.56 to 1.22; n = 6 carriers) lower CRP level
      compared with the most common haplotype with a frequency of 1% (global P-value =
      0.048). No association was detected between CRP gene variation and CVD risk in
      either whites or African Americans. CONCLUSION: Compared with the most common
      haplotype of the CRP gene, 1 haplotype predicts a lower serum CRP level over
      time, but no association exists between haplotype of CRP gene and incident CVD in
      this incident dialysis population. Serum CRP level might be a biomarker, rather
      than a causal factor, in CVD development. CRP variation may lead to
      susceptibility to inflammation, but not risk for CVD; however, replication in
      multiple settings is necessary.

PMID- 17185153
TI  - Platelet FcgammaRIIA receptor surface expression is increased in patients with
      ESRD and is associated with atherosclerotic cardiovascular events.
AB  - BACKGROUND: Accelerated atherogenesis is a prominent feature of end-stage renal
      disease (ESRD). METHODS: Expression of platelet FcgammaRIIA immunoglobulin G
      receptor (FcgammaR) was measured in 2 populations: (1) 48 patients with ESRD with
      a mean age of 50.7 +/- 2.3 (SEM) years and (2) 48 healthy age- and sex-matched
      controls aged 53.6 +/- 1.6 years. RESULTS: Platelet FcgammaR expression was
      enhanced significantly in patients with ESRD (mean fluorescence intensity [MFI],
      7.88 +/- 0.42 [SEM]; 95% confidence interval [CI], 7.03 to 8.72 versus 5.07 +/-
      0.21; 95% CI, 4.64 to 5.49; P < 0.0001). In patients with ESRD, multivariate
      analysis showed that hemoglobin level and diastolic blood pressure were related
      inversely to FCgammaR expression (P = 0.01 and P = 0.03, respectively).
      Atherosclerotic cardiovascular events (ACVEs) were recorded prospectively for the
      ESRD cohort. A total of 22 ACVEs, defined as the occurrence of myocardial
      infarction (10 events), cerebrovascular accident (7 events), and/or a peripheral
      vascular event (5 events), were observed. In the group with greater receptor
      expression (MFI > 7.785; n = 24), 13 of 17 patients (76.5%) experienced at least
      1 ACVE, whereas only 4 of 17 patients (23.5%) with low FcgammaR expression (MFI <
      7.785; n = 24) experienced an event (P = 0.007). CONCLUSION: (1) Uremia is
      associated with enhanced platelet FcgammaR expression, and (2) patients with
      greater platelet FcgammaR expression are significantly more likely to experience
      ACVEs; however, (3) the small sample size is a limitation and our work therefore
      is a hypothesis-generating pilot study that remains to be confirmed.

PMID- 17185154
TI  - EPO adjustments in patients with elevated hemoglobin levels: provider practice
      patterns compared with recommended practice guidelines.
AB  - BACKGROUND: This study investigates provider practices regarding recombinant
      human erythropoietin (rHuEPO) dose when patient hemoglobin levels exceeded
      National Kidney Foundation-Dialysis Outcomes Quality Initiative target levels and
      reached 13 g/dL or greater (>or=130 g/L). METHODS: The study population (N =
      167,796) was hemodialysis patients prevalent on January 1, 2003, who were on
      renal replacement therapy at least 90 days with Medicare as primary payer and
      rHuEPO claims in 2 or more consecutive months. Patient characteristics were
      obtained from the Centers for Medicare & Medicaid Services (CMS) Medical Evidence
      Report, and comorbid conditions were determined from Medicare claims. Providers
      and rHuEPO claims were linked by using CMS-assigned provider numbers and the CMS
      Annual End-Stage Renal Disease Facility Survey. Between-provider differences in
      patient characteristics were examined by using chi-square test, and provider
      effect on appropriate response, by using logistic regression. RESULTS: DaVita's
      percentage of monthly claims for patients with hemoglobin levels of 13 g/dL or
      greater (>or=130 g/L; 16.7%) and mean monthly rHuEPO dose (54,299 units) were
      highest. Dialysis Clinic Inc's percentage of such claims (2.0%) and mean monthly
      dose (38,687 units) were lowest. Dialysis Clinic Inc, Fresenius, and Renal Care
      Group had the highest percentage of recommended dose adjustments (mean, 70% of
      units); hospital-based units had the lowest (59%). By adjusted odds ratio,
      adjustments were 20% more likely for Dialysis Clinic Inc, Fresenius, and Renal
      Care Group compared with DaVita, National Nephrology Associates, hospital-based
      units, and independents (17% to 28% less likely). CONCLUSION: rHuEPO dose
      reduction practices are dependent on specific dialysis providers and whether
      units are hospital based or independent.

PMID- 17185156
TI  - Acute oxalate nephropathy associated with orlistat, a gastrointestinal lipase
      inhibitor.
AB  - Orlistat is an oral inhibitor of gastrointestinal lipase used for weight
      reduction in obese patients. Although most adverse drug effects manifest in the
      gastrointestinal tract, this is the first reported case of orlistat-induced acute
      kidney injury secondary to acute oxalate nephropathy in a white woman with
      underlying chronic kidney disease. Acute kidney injury was associated temporally
      with an increased dose of orlistat and the development of increased fat
      malabsorption (more frequent loose oily stools). Urine sediment showed abundant
      calcium oxalate crystals and increased 24-hour urine oxalate concentration.
      Kidney biopsy showed deposition of calcium oxalate crystals within tubular
      lumens, consistent with acute oxalate nephropathy. Orlistat therapy was
      discontinued, and oral fluid intake was increased. A second kidney biopsy
      performed 1 month later to evaluate the slow resolution of kidney failure did not
      show calcium oxalate crystals within tubules. A steady improvement in renal
      function subsequently was observed. Results of a repeated 24-hour urine oxalate
      collection performed 3 weeks later when kidney function had improved were within
      normal limits.

PMID- 17185155
TI  - Coronary artery calcification and chronically decreased GFR in living kidney
      donors.
AB  - BACKGROUND: In the presence of decreased glomerular filtration rate (GFR), the
      risk of morbidity and mortality caused by cardiovascular disease (CVD) is
      increased markedly. Increased coronary artery calcification (CAC) is proposed as
      a pathogenetic link between CVD and chronic kidney disease. We examined the
      frequency and severity of CAC in living kidney donors to test the hypothesis that
      decreased GFR is associated with increased CAC. METHODS: We used multidetector
      spiral computed tomography to examine CAC in 101 living kidney donors and 99 age-
      and sex-matched healthy control subjects without diabetes and a history of
      coronary artery disease. The extent of calcification was measured by means of the
      Agatston score. GFR was calculated by using the abbreviated Modification of Diet
      in Renal Disease formula. The frequency of risk factors for coronary artery
      disease was compared in kidney donors and controls, and the relation between
      kidney donors' clinical characteristics and the presence or absence of CAC was
      examined. RESULTS: CAC frequency and mean calcification scores were similar
      between kidney donors (13.9%; 4.5 +/- 22.6) and controls (17.2%; 13.2 +/- 89.2).
      CAC was not associated with decreased GFR, and the correlation between CAC and
      GFR was not statistically significant. Kidney donors with calcification were more
      likely to be older (P = 0.003) and male (P = 0.001). Age- and sex-adjusted
      analysis showed an association between greater parathormone levels (odds ratio,
      1.023; 95% confidence interval, 1.001 to 1.045; P = 0.037) and CAC in kidney
      donors. CONCLUSION: A mild decrease in GFR without the presence of diabetes does
      not seem to be associated with increased CAC. These findings need to be confirmed
      in different and larger study populations.

PMID- 17185157
TI  - Unexpected efficacy of rituximab in multirelapsing minimal change nephrotic
      syndrome in the adult: first case report and pathophysiological considerations.
AB  - Nephrotic syndrome secondary to minimal change disease (MCNS) usually is
      considered to have a good renal prognosis, but frequency of relapses and steroid
      dependency are therapeutic challenges to physicians. Treatment of patients with
      multiple relapses remains controversial because few control studies are
      available. We report the case of a 23-year-old woman of Malian origin who
      experienced more than 30 relapses of MCNS. Long-term remission was observed only
      with rituximab (anti-CD20 antibody) treatment after step-by-step use of all
      currently available medications for MCNS were unsuccessful. Our observation is
      the first report of efficacy of rituximab during multirelapsing MCNS in an adult
      patient with a significant follow-up and no adjuvant therapy. This case suggests
      a role of B cells in MCNS, possibly by regulating T-cell function.

PMID- 17185158
TI  - Chronic kidney disease.

PMID- 17185159
TI  - "Biased" comparison between ANDY-Disc and UltraBag in patients on CAPD.

PMID- 17185163
TI  - Comparative expression analysis of members of the Hsp70 family in the
      chytridiomycete Blastocladiella emersonii.
AB  - Sequencing of a large number of expressed sequence tags from Blastocladiella
      emersonii revealed the presence of ten distinct putative members of the 70 kDa
      heat shock protein (Hsp70) family in this fungus. The amino acid sequence deduced
      from eight of these cDNAs showed significant similarity to members of the
      Saccharomyces cerevisiae Hsp70 family, and the remaining displayed high sequence
      homology with hsp70 gene products from other organisms. The hsp70-3 gene was the
      most highly expressed at normal temperatures and was poorly induced during heat
      shock. Except for hsp70-4 and hsp70-6, all other hsp70 genes were induced to
      different degrees upon exposure of B. emersonii cells to heat shock, with hsp70-1
      gene presenting the highest transcript levels. Phylogenetic analysis of complete
      B. emersonii putative Hsp70 protein sequences indicated that Hsp70-1 and Hsp70-3
      corresponded to cytosolic proteins, whereas Hsp70-7 and Hsp70-9 are probably
      localized in the endoplasmic reticulum and mitochondria, respectively.

PMID- 17185164
TI  - Fluorescent multiplex amplification of three X-STR loci.
AB  - This study was carried out to evaluate the value of three X-STR loci (DXS6803,
      DXS981and DXS6809) in forensic application and thereby investigate their
      polymorphism. The primer for each locus was labeled with fluorochrome 6-FAM. A
      fluorescent multiplex PCR for simultaneously amplifying three X-STR loci was set
      up. The PCR products that were obtained were analyzed using capillary
      electrophoresis and ABI PRISM 3100 Genetic Analyzer, with GENESCAN Analysis
      Software. When 340 male and 195 female individuals of Han population in China
      were tested, 13, 12, and 11 alleles were observed for DXS6803, DXS981 and
      DXS6809, respectively. One hundred and eighty three haplotypes were detected in
      the male individuals. The haplotype diversity reached 0.9926. The results show
      that the three loci of the multiplex system provide significant information on
      polymorphism for forensic identification and paternity testing, particularly for
      complicated paternity deficient cases.

PMID- 17185166
TI  - Comparison of different foreground and background selection methods in marker
      assisted introgression.
AB  - Three different methods for foreground selection and four different methods for
      background selection were compared in terms of the efficiency of marker-assisted
      introgression of a QTL allele from a donor line into a recipient line and also in
      terms of the recovery of the recipient genetic background. The results showed
      that for the introgression of a donor QTL allele, a direct selection on the QTL
      itself (when the QTL genotype can be directly identified) would ensure that the
      allele is successfully introgressed and rapidly fixed. However, when a direct
      selection on the QTL is not feasible, an indirect selection using two closely
      linked flanking markers can be used, which also shows similar results. For the
      recovery of the recipient genetic background, if the goal is to recover the whole
      genetic background of the recipient, genomic similarity selection or marker index
      selection would be the best choice: Only three generations of backcrosses were
      required to recover over 98% of the recipient genome. Whereas if the goal is to
      recover certain background traits of the recipient, MBLUP selection would give
      the best results, which achieved not only over 99% recovery of the recipient QTL
      alleles for the background traits after three generations of backcrosses, but
      also showed the best genetic improvement of these traits.

PMID- 17185165
TI  - Y-chromosome genotyping and genetic structure of Zhuang populations.
AB  - Zhuang, the largest ethnic minority population in China, is one of the descendant
      groups of the ancient Bai-Yue. Linguistically, Zhuang languages are grouped into
      northern and southern dialects. To characterize its genetic structure, 13 East
      Asian-specific Y-chromosome biallelic markers and 7 Y-chromosome short tandem
      repeat (STR) markers were used to infer the haplogroups of Zhuang populations.
      Our results showed that O*, O2a, and O1 are the predominant haplogroups in
      Zhuang. Frequency distribution and principal component analysis showed that
      Zhuang was closely related to groups of Bai-Yue origin and therefore was likely
      to be the descendant of Bai-Yue. The results of principal component analysis and
      hierarchical clustering analysis contradicted the linguistically derived north
      south division. Interestingly, a west-east clinal trend of haplotype frequency
      changes was observed, which was supported by AMOVA analysis that showed that
      between-population variance of east-west division was larger than that of north
      south division. O* network suggested that the Hongshuihe branch was the center of
      Zhuang. Our study suggests that there are three major components in Zhuang. The
      O* and O2a constituted the original component; later, O1 was brought into Zhuang,
      especially eastern Zhuang; and finally, northern Han population brought O3 into
      the Zhuang populations.

PMID- 17185167
TI  - Analysis of the genetic diversity and the phylogenetic evolution of Chinese sheep
      based on Cyt b gene sequences.
AB  - The complete sequences of Cyt b gene from 20 individuals belonging to eight
      Chinese indigenous sheep breeds and one foreign breed were studied. The results
      showed that the hapolotype diversity of Chinese sheep breeds was 97.1%. The mean
      nucleotide composition of all the sequences was 27.1% T, 28.5% C, 31.4% A, and
      13.0% G. The nucleotide diversity was 0.602%. A total of 43 mutation sites were
      detected, including 40 transitions and 3 transversions. Fu's test of selective
      neutrality showed that the sheep populations had no population demographic
      expansion (0.10 >P > 0.05). The different clustering methods, namely neighbor
      joining, minimum evolution, and unweighted pair group method with arithmetic
      means, all showed a similar result, which indicated that Chinese local sheep had
      three maternal resources.

PMID- 17185168
TI  - Study on tandem repeat sequence variation in sheep mtDNA D-loop region.
AB  - The 75-nt-long tandem repeat sequence in the control region of mtDNA of 77
      individuals, of which 69 were from different indigenous sheep breeds in China and
      8 were from imported breeds, was sequenced and analyzed to investigate the origin
      and differentiation of Chinese indigenous sheep breeds and also the genetic
      diversities and relationships among them. A total of 28 variable sites were
      detected within 309 repeated sequences, among which 7 sites were singleton
      variable sites with two variants, 1 site was a singleton variable site with three
      variants, and 20 sites were parsimony informative sites with two variants. A
      total of 63 haplotypes were sorted from 28 polymorphic sites, among which two
      main and basic haplotypes, namely, Hap 1 and Hap 3 were present at a much higher
      proportion, at 12.94% and 30.42%, respectively. It could be inferred that Chinese
      indigenous sheep breeds originated from two maternal ancestors because of the
      maternal inheritance characteristics of the mtDNA. Altay sheep and Kazakstan
      sheep are closely related and do not differentiate significantly. Mongolian sheep
      and Ujumuqin sheep also share a close relationship. Tibetan sheep, Mongolian
      sheep, and Ujumuqin sheep have lower genetic diversity than Altay sheep and
      Kazakstan sheep.

PMID- 17185169
TI  - Molecular cloning of bovine FABGL gene and its effects on bovine bioeconomic
      traits.
AB  - The complete CDS sequence of the bovine FABGL gene was determined by homology
      cloning approach combined with RT-PCR and 3'- and 5'-RACE. The results of
      sequence analysis and bioinformatics study showed that this cDNA contained 994
      nucleotides, with a 780 bp open reading frame (ORF) flanked by a 16 bp 5'-UTR
      (incompletely) and a 198 bp 3'-UTR. The deduced amino acid sequence (260 AA)
      shows 88% identity with the corresponding sequence in humans. Two single
      nucleotide substitutions, one located in intron 5 (I5) at position 1 065 bp (Y =
      C/T) (GenBank: DQ409814) and the other in intron 8 (I8) at position 1 792 bp (R =
      A/G), were detected using the PCR-SSCP method. Analysis of the allele frequencies
      of the two polymorphic sites in three different cattle breeds (Angus, Hereford,
      and Simmental) with different genotypes showed large differences: in locus I8,
      cattle with the GG genotype showed higher beef performance index (BPI) (4.283 +/-
      0.475 kg/cm) in comparison with cattle with the AA genotype (4.008 +/- 0.465
      kg/cm) (P = 0.01). Regarding the ribeye area, cattle with the GG genotype showed
      significantly higher ribeye area (73.380 +/- 13.005 cm(2)) compared with cattle
      with the AA genotype (67.744 +/- 12.777 cm(2)) (p = 0.05). In locus I5, some
      associations for the average daily gain (ADG) were found at the significance
      level of 0.01 between three different genotypes (CC, CT, TT): cattle with the TT
      genotype showed the highest ADG (0.652 +/- 0.330 kg/d), whereas cattle with the
      CC genotype showed the lowest ADG value (0.421 +/- 0.178 kg/d).

PMID- 17185170
TI  - Inheritance analysis of herbicide-resistant transgenic soybean lines.
AB  - Four transgenic soybean lines generated via Agrobacterium-mediated transformation
      were used to analyze inheritance of the transgenes. Seed chip GUS assay and
      herbicide leaf painting and spraying assays were applied to test the gus reporter
      gene and the herbicide resistant bar selectable marker gene, respectively. Three
      of the four transgenic soybean lines were stably inherited in a Mendelian fashion
      with co-segregation of both transgenes in a 3:1 segregation ratio in the T(1)
      progeny, indicating that both transgenes were integrated into the same locus of
      the soybean genome. Homozygous transgenic progeny plants were obtained in the
      T(2) generation of these lines, and the transgenes were inherited in five
      successive generations. However, in one transgenic line, all the T(1) progeny
      plants showed GUS negative and herbicide sensitive. Southern blotting analysis
      confirmed that the transgenes were passed into the T(1) progeny, indicating that
      the transgenes were both silenced. To test if the transgene silencing was due to
      transcriptional or post-transcriptional level, Soybean mosaic virus (SMV) was
      inoculated on leaf tissues of the T(1) plants to test possible reverse effects on
      transgene silencing. Infection with SMV did not suppress transgene silencing,
      suggesting that transgene silencing in this transgenic line may not be due to
      post-transcriptional gene silencing.

PMID- 17185171
TI  - Ultrastructure and gene mapping of the albino mutant al12 in rice (Oryza sativa
      L.).
AB  - Seedling albino mutation resistant to low temperature is an adaptability of rice
      (Oryza sativa L.) to cold. The mutant, a conditional expression controlled by
      development and temperature, differs from other albino mutants. The chlorophyll
      content of the mutant was measured using a portable chlorophyll meter, and the
      ultrastructure of the chloroplast was observed using a transmission electron
      microscope. Chlorophyll content was 1.2 SPAD, and the chloroplast did not
      develop, with only small vesicle-like structures. A segregation analysis of the
      reciprocal crosses between the albino mutation line with the rice line 9311
      demonstrated that the albino trait was controlled by a single recessive gene,
      which was flanked by SSR markers RM5068 and RM3702 on the short arm of chromosome
      8 with a distance of 0.5-1.1 cM and 4.9 cM, respectively. This gene was mapped
      within a 6 cM interval region and was tentatively referred to as al12.

PMID- 17185172
TI  - Differential expression of endogenous ferritin genes and iron homeostasis
      alteration in transgenic tobacco overexpressing soybean ferritin gene.
AB  - For studying the effects of endogenous ferritin gene expressions (NtFer1, GenBank
      accession number AY083924; and NtFer2, GenBank accession number AY141105) on the
      iron homeostasis in transgenic tobacco (Nicotiana tabacum L.) plants expressing
      soybean (Glycine max Merr) ferritin gene (SoyFer1, GenBank accession number
      M64337), the transgenic tobacco has been produced by placing soybean ferritin
      cDNA cassette under the control of the CaMV 35S promoter. The exogenous gene
      expression was examined by both Northern- and Western-blot analyses. Comparison
      of endogenous ferritin gene expressions between nontransformant and transgenic
      tobacco plants showed that the expression of NtFer1 was increased in the leaves
      of transgenic tobacco plants, whereas the NtFer2 expression was unchanged. The
      iron concentration in the leaves of transgenic tobacco plants was about 1.5-folds
      higher than that in nontransformant. Enhanced growth of transgenic tobacco was
      observed at the early development stages, resulting in plant height and fresh
      weights significantly greater than those in the nontransformant. These results
      demonstrated that exogenous ferritin expression induced increased expression of
      at least one of the endogenous ferritin genes in transgenic tobacco plants by
      enhancing the ferric chelate reductase activity and iron transport ability of the
      root, and improved the rate of photosynthesis.

PMID- 17185173
TI  - Analysis of the phylogenetic relationships among several species of Gramineae
      using ACGM markers.
AB  - To study the transferability of rice (Oryza sativa L.) genome data, we used
      amplified consensus genetic markers to analyze the phylogenetic relationships
      among several species and genera in Gramineae. Ten accessions representing five
      grass genera (Oryza, Zea, Setaria, Triticum, and Phyllostachys) were used.
      According to the genetic distances, a cluster tree was constructed. The
      relationships among the five genera could be simply described as ((Oryza + (Zea
      +Setaria)) +Triticum) +Phyllostachys. The results suggest that the genetic
      distance between rice and maize (Z. mays L.) or rice and millet (Setaria italica
      L.) is closer than that between rice and wheat (Triticum aestivum L) or rice and
      bamboo.

PMID- 17185174
TI  - Powers of multiple-testing procedures for identification of genes significantly
      differentially expressed in microarray experiments.
AB  - Because of the high operation costs involved in microarray experiments, the
      determination of the number of replicates required to detect a gene significantly
      differentially expressed in a given multiple-testing procedure is of considerable
      significance. Calculation of power/replicate numbers required in multiple-testing
      procedures provides design guidance for microarray experiments. Based on this
      model and by choice of a multiple-testing procedure, expression noises based on
      permutation resampling can be considerably minimized. The method for mixture
      distribution model is suitable to various microarray data types obtained from
      single noise sources, or from multiple noise sources. By using the biological
      replicate number required in microarray experiments for a given power or by
      determining the power required to detect a gene significantly differentially
      expressed, given the sample size, or the best multiple-testing method can be
      chosen. As an example, a single-distribution model of t-statistic was fitted to
      an observed microarray dataset of 3 000 genes responsive to stroke in rat, and
      then used to calculate powers of four popular multiple-testing procedures to
      detect a gene of an expression change D. The results show that the B-procedure
      had the lowest power to detect a gene of small change among the multiple-testing
      procedures, whereas the BH-procedure had the highest power. However, all multiple
      testing procedures had the same power to identify a gene having the largest
      change. Similar to a single test, the power of the BH-procedure to detect a small
      change does not vary as the number of genes increases, but powers of the other
      three multiple-testing procedures decline as the number of genes increases.

PMID- 17185176
TI  - The dispersed neuroendocrine system, its bronchopulmonary elements, and
      neuroendocrine tumors presumed to be derived from them: myths, mistaken notions,
      and misunderstandings.
AB  - The increasing recognition of the dispersed neuroendocrine system and its
      importance in human physiology has impacted our understanding of physiology,
      pathophysiology, and histopathology. It has been the subject of a great deal of
      controversy and debate, giving rise to certain misunderstandings. This article
      attempts to put some of these issues in perspective, especially as they relate to
      the bronchopulmonary tree.

PMID- 17185177
TI  - Approach to the diagnosis of neuroendocrine lung neoplasms: variabilities and
      pitfalls.
AB  - With the publication of the spectrum of neuroendocrine proliferations and
      neoplasms and the features and criteria for diagnosing neuroendocrine lung
      neoplasms, there is more agreement in making a specific pathologic diagnosis of a
      neuroendocrine lung neoplasm. However, problems exist, especially in diagnosing
      well-differentiated neuroendocrine carcinomas (atypical carcinoids), large-cell
      neuroendocrine carcinomas, and even some small-cell lung cancers. Some of this
      disagreement has to do with a pathologist's perception of sizes and shapes of
      cells. Nonneuroendocrine small-cell carcinomas exist and include small-cell
      squamous cell carcinoma, small cell adenocarcinoma, and basaloid carcinoma.
      Nonneuroendocrine lung cancers, especially large-cell undifferentiated carcinoma
      and poorly differentiated adenocarcinoma, not infrequently express neuroendocrine
      markers immunohistochemically.

PMID- 17185178
TI  - Bronchial typical carcinoid tumors.
AB  - The current WHO classification of lung tumors recognizes bronchial typical
      carcinoid as low-grade neuroendocrine tumors. These tumors grow slowly but can
      metastasize to regional nodes (4 to 20%) and more rarely to extrathoracic sites.
      Symptoms are usually related to local compression and obstruction of the
      bronchial tree. Paraneoplastic syndrome can be present (carcinoid syndrome,
      Cushing's syndrome, acromegaly). Preoperative diagnosis is usually obtained with
      bronchoscopic biopsy. Computed tomography and somatostatin receptor scintigraphy
      are useful in the preoperative staging. Only selected cases can be treated
      endoscopically with laser resection. The complete surgical resection remains the
      only therapy with curative intent in the majority of patients. Parenchyma-sparing
      resections are indicated whenever possible. Overall survival after surgery is
      excellent (5-year rate, 87 to 100%) with low recurrence rate (2 to 11%). N-status
      and type of resection seem not to affect prognosis. Local relapse can be treated
      successfully with surgery, whereas distant metastases have a poor prognosis even
      after chemotherapy.

PMID- 17185179
TI  - Well-differentiated neuroendocrine carcinomas: the spectrum of histologic
      subtypes and various clinical behaviors.
AB  - The term "well-differentiated neuroendocrine carcinoma" was coined to describe a
      variety of demonstrably neuroendocrine tumors which were more aggressive (both
      with respect to their histologic appearance and their clinical course) than
      (typical) bronchial carcinoids but were also clearly distinguishable from small
      cell neuroendocrine carcinomas. This umbrella term encompasses a variety of
      tumors previously described by a variety of terms including "atypical"
      carcinoids, "malignant tumorlets," peripheral stage I small-cell carcinoma, as
      well as neoplasms described simply as "undifferentiated carcinoma" (prior to the
      recognition of their neuroendocrine properties). As such, this term is a broad
      term and is not simply synonymous with "atypical carcinoid." Over time, at least
      3 subtypes have been identified based upon their histologic appearance and
      mitotic index, with correspondingly aggressive clinical courses.

PMID- 17185180
TI  - Large-cell neuroendocrine carcinoma of the lung: an aggressive neuroendocrine
      lung cancer.
AB  - Large cell neuroendocrine carcinoma (LCNEC) is part of the neuroendocrine
      spectrum of pulmonary tumors. This increasingly recognized tumor has been
      reported to have 5-year actuarial survival rates following resection that are
      worse than those described for other variants of non-small cell lung cancer
      (NSCLC). Therefore, debate has emerged regarding whether the tumors should be
      classified and treated as NSCLC or small-cell lung cancer. This article reviews
      the tumor characterization, biology, presentation and diagnosis, surgical
      therapy, results of therapy, and long term prognosis of patients with LCNEC.

PMID- 17185181
TI  - Surgery for small-cell lung cancer.
AB  - Treatment of small-cell lung cancer (SCLC) is typically chemotherapy with or
      without radiation, depending on the extent of disease. There are several
      situations where surgery may have a role to play. Patients with clinical stage T1
      2 N0 SCLC may benefit from surgery for confirmation of diagnosis and improved
      local control when combined with chemotherapy. Surgery itself rarely contributes
      to prolonged survival for N2 SCLC. In this view, mediastinoscopy is recommended
      to exclude N2 disease before surgery is considered. Patients with a combined
      histology tumor (mixtures of SCLC with non-SCLC components) may be offered
      surgery since the non-SCLC component is less sensitive to chemotherapy and
      resection may contribute to cure. Salvage surgery should be considered for
      patients having relapse only in the primary site or a localized chemotherapy
      resistant tumor, which can occur because of an unrecognized mixed tumor. Recent
      evidence has shown that platinum-based chemotherapy with concurrent
      hyperfractionated radiotherapy followed by surgery is feasible and a promising
      strategy for highly selected patients with SCLC. Among patients with nodal
      disease, only those with negative nodes following induction
      chemo/chemoradiotherapy should be candidates for surgery, which may offer
      improved local control. Further evidence for this strategy will be obtained from
      ongoing randomized clinical trials.

PMID- 17185183
TI  - Historical perspective: surgery for chronic thromboembolic disease.
AB  - This article provides a historical perspective for our current understanding of
      chronic thromboembolic pulmonary hypertension and surgery for this disease. It
      chronicles the developments in surgical techniques that have made pulmonary
      endarterectomy the procedure of choice for obstruction of pulmonary vessels by
      organized thromboemboli and secondary vessel wall thickening.

PMID- 17185184
TI  - Evaluation of patients for pulmonary endarterectomy.
AB  - Chronic thromboembolic obstruction of the pulmonary vascular bed has been
      increasingly recognized as a treatable form of pulmonary hypertension, with
      surgery referred to as a pulmonary endarterectomy. Careful evaluation of patients
      with pulmonary hypertension and proper selection of those with surgically
      accessible, chronic thromboembolic disease are critical determinants for a
      successful outcome from this operation. This article describes the clinical
      presentation, appropriate evaluation, and an approach to surgical selection for
      patients with chronic thromboembolic pulmonary hypertension.

PMID- 17185185
TI  - Echocardiography in chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a significant
      complication of venous thromboembolism and is caused by incomplete resolution of
      pulmonary emboli. The persistent chronic pulmonary hypertension leads to right
      ventricle pressure overload. As a result, there is often significant functional
      and morphological alteration of both the right and the left ventricle.
      Transthoracic echocardiography, which allows for the estimation of pulmonary
      arterial pressures, not only plays an important role in the diagnosis of
      pulmonary hypertension but also provides insights in the pathophysiology of
      CTEPH. This article reviews the echocardiographic techniques and findings in
      CTEPH patients.

PMID- 17185187
TI  - Technical advances of pulmonary endarterectomy for chronic thromboembolic
      pulmonary hypertension.
AB  - Pulmonary endarterectomy is the definitive treatment for chronic pulmonary
      hypertension as the result of thromboembolic disease. Although significant
      progress has been made over the last decade in recognition, diagnostic
      modalities, and treatment of this disease, chronic thromboembolic pulmonary
      hypertension (CTEPH) continues to be severely underdiagnosed and as a consequence
      pulmonary endarterectomy remains an uncommon procedure. Patients with CTEPH may
      present with a variety of debilitating cardiopulmonary symptoms. However, once
      diagnosed, there is no curative role for medical management, and surgery remains
      the only option. Medical management in these patients is only palliative, and
      surgery by means of transplantation for this type of pulmonary hypertension is an
      inappropriate use of resources with less than satisfactory results. In this
      article we describe the technical advances of pulmonary endarterectomy and the
      current procedure as it is performed at University of California-San Diego
      Medical Center.

PMID- 17185186
TI  - Anesthesia for pulmonary endarterectomy.
AB  - Anesthetic care for patients undergoing pulmonary endarterectomy represents one
      of the most challenging tasks in cardiac anesthesia. Chronic thromboembolic
      pulmonary hypertension with its concomitant right ventricular failure may cause
      hemodynamic instability during anesthetic induction and the precardiopulmonary
      bypass (CPB) period, and the associated comorbidities (pulmonary, hepatic) may
      affect the actions and metabolism of anesthetic drugs. During the CPB period,
      proper perfusion patterns, cerebral oxygenation, and adequate hypothermia for
      deep hypothermic circulatory arrest must be achieved. During the post-CPB period
      the anesthesiologist must be prepared to treat residual pulmonary hypertension,
      pulmonary edema, pulmonary bleeding, right ventricular failure, and various
      metabolic and cardiovascular sequelae of hypothermic circulatory arrest. This
      review highlights the main issues the anesthesiologist faces during pulmonary
      endarterectomy, as well as suggests approaches to their management.

PMID- 17185188
TI  - Postoperative management of the patient undergoing pulmonary endarterectomy.
AB  - The postoperative care of the patient undergoing pulmonary endarterectomy
      presents challenges that occur not only with other types of cardiac surgery but
      also with significant respiratory system changes related to alterations in
      pulmonary blood flow. Postoperative mortality associated with this procedure has
      declined substantially over the years as a consequence of improved evaluative
      procedures and selective surgical referral, advances in surgical technique, and
      an understanding of the unique postoperative complications that may occur.
      However, postoperative acute lung injury and residual pulmonary hypertension
      continue to represent major causes of mortality associated with this procedure
      and represent areas where additional investigative efforts are necessary. Here we
      describe the unique hemodynamic and respiratory changes that occur in the
      postoperative pulmonary endarterectomy patient and an evidence-based approach to
      their optimal management.

PMID- 17185189
TI  - Outcomes of pulmonary endarterectomy surgery.
AB  - Chronic thromboembolic pulmonary hypertension has emerged as one of the leading
      causes of severe pulmonary hypertension. This disease is estimated to occur in
      approximately 1 to 5% of all patients who have previously developed an acute
      pulmonary embolism, although the true prevalence is suspected to be much higher.
      Chronic thromboembolic pulmonary hypertension is characterized by intraluminal
      thrombus organization, fibrous stenosis, and vascular remodeling of pulmonary
      vessels. Pulmonary endarterectomy is an operation that is considered curative for
      thromboembolic pulmonary hypertension and is therefore superior to
      transplantation for this condition. This article focuses on the surgical outcomes
      of patients undergoing pulmonary endarterectomy for chronic thromboembolic
      pulmonary hypertension and discusses the currently known factors that affect
      survival after this operation.

PMID- 17185190
TI  - Molecular biology of chronic thromboembolic pulmonary hypertension.
AB  - Recent efforts have seen major advances in elucidating the mechanisms underlying
      pulmonary arterial hypertension. However, chronic thromboembolic pulmonary
      hypertension (CTEPH) often has been excluded from these studies. Consequently,
      whereas the clinical, radiographic, and hemodynamic characteristics of CTEPH have
      been well described, there remains a deficit in our understanding of the
      cellular, molecular, and genetic mechanisms underlying CTEPH. Furthermore,
      although prior venous thromboembolism may act as the inciting event, it is still
      unclear what predisposes some patients to develop CTEPH. CTEPH has two major
      pathogenic components. The first is the primary obstruction of central pulmonary
      arteries by accumulation of thrombotic material. The second is characterized by
      severe pulmonary vascular remodeling, similar to that seen in idiopathic
      pulmonary arterial hypertension. Other articles in this series describe the
      pathological, surgical, and therapeutic aspects of CTEPH. Here, we review the
      potential molecular and cellular mechanisms that may contribute to the
      pathogenesis of CTEPH.

PMID- 17185192
TI  - Epidemiology and pathogenesis of esophageal cancer.
AB  - Esophageal cancer remains an important public health problem worldwide.
      Understanding and preventing the occurrence of this cancer are complicated by the
      fact that the 2 major histologic types, squamous cell carcinoma (SCC) and
      adenocarcinoma (ACE), differ substantially in their underlying patterns of
      incidence and key etiologic factors. The main characteristic that they share is a
      high mortality rate. Surveillance, Epidemiology, and End Results data for the
      United States show a 30% drop in incidence of SCC between 1973 and 2002, with
      declines greatest in black males, although incidence in this group remains high
      compared with other groups. Incidence of ACE has increased 4-fold over the same
      period, with a nearly 5-fold increase in white males. Alcohol and smoking are
      major, established risk factors for SCC. Gastroesophageal reflux disease is
      consistently associated with increased risk of ACE, whereas infection with
      Helicobacter pylori may reduce its incidence. Increasing body mass index is also
      strongly associated with ACE risk while showing no association or an inverse
      relationship with SCC. Diet affects both types of esophageal cancer, with a
      higher intake of fruits and vegetables associated with reduced incidence. Aspirin
      and other nonsteroidal antiinflammatory drugs are currently the most promising
      chemoprevention candidates for both cancer types. Lifestyle changes, such as
      weight loss and exercise, are additional ways in which the incidence of ACE might
      be reduced.

PMID- 17185193
TI  - Endoscopic therapy of dysplasia and early-stage cancers of the esophagus.
AB  - Endoscopic treatments have become a viable alternative for some patients with
      early-stage esophageal neoplasia. Although esophagectomy remains the standard of
      care for high-grade dysplasia and superficial cancers, surgical morbidity and
      mortality may deter patients who are medically unfit or reluctant to undergo
      surgery. Photodynamic therapy (PDT) and endoscopic mucosal resection (EMR) are
      the best-studied nonsurgical approaches at present. PDT has been reported to
      eradicate high-grade dysplasia (HGD) and early Barrett's cancers at rates ranging
      from 75% to 100% and 17% to 100%, respectively, and a recent randomized
      controlled trial confirmed that PDT may prevent progression of HGD to cancer.
      Complete remission rates greater than 90% have also been reported with EMR and
      other mucosa-ablating interventions, although recurrence rates necessitate close
      endoscopic surveillance and retreatment in some patients. In addition to PDT and
      EMR, several emerging endoscopic treatment options for superficial esophageal
      neoplasia may provide attractive alternatives to surgery.

PMID- 17185194
TI  - Definitive chemoradiation in the management of locally advanced esophageal
      cancer.
AB  - A significant number of patients diagnosed with esophageal cancer will present
      with locally advanced disease. The appropriate management of these patients
      continues to be a matter of significant debate. Over the past 2 decades,
      concurrent chemoradiation has been widely recognized as a viable option for a
      majority of these patients. Although there have been no randomized trials
      comparing definitive chemoradiation with surgical resection, there is little
      doubt that nonoperative therapy offers comparative opportunity for cure with less
      intendent morbidity and mortality. The broad applicability of this treatment
      option has led investigators to study methods of maximizing the therapeutic gain
      associated with the combination of external beam radiation and systemic
      chemotherapy. The long-term survival results have compared favorably with
      surgical series, thus leading to clinical trials designed to define the role of
      surgery in future management strategies. The early evaluation of these recent
      trials fails to identify any significant advantage associated with the routine
      use of surgery for most patients. Recent advances in drug development in
      conjunction with the identification of specific molecular targets has provided
      new opportunities to improve on the outcomes achieved with standard
      chemoradiation combinations.

PMID- 17185195
TI  - The role of integrated computed tomography positron-emission tomography in
      esophageal cancer: staging and assessment of therapeutic response.
AB  - Computed tomography (CT) and endoscopy/endoscopic ultrasonography are usually
      performed to initially stage patients with esophageal cancer, to determine
      primary tumor response, and to detect nodal and distant metastases after
      preoperative therapy. Positron-emission tomography (PET) with [18F]-fluoro-2
      deoxy-D-glucose and integrated CT-PET are useful in the initial staging of
      patients with esophageal cancer as well as in the prediction of pathologic
      response, disease-free interval, and overall survival after preoperative therapy.
      Importantly, integrated CT-PET imaging decreases the number of futile attempts at
      surgical resection, mainly because of the detection of occult distant metastases.
      The following sections review the use of integrated CT-PET imaging in determining
      the T, N, and M descriptors of the American Joint Commission on Cancer's 2002
      guidelines for pathologic and clinical staging at initial diagnosis and after
      chemoradiation therapy in those patients being considered for surgical resection.

PMID- 17185196
TI  - Are squamous and adenocarcinomas of the esophagus the same disease?
AB  - Esophageal cancer can be divided in squamous-cell cancer (SCC) and adenocarcinoma
      (Barrett cancer: AEG I) by histopathology. However, most studies do not
      differentiate between these two tumor entities. SCC is associated with a lower
      socioeconomic level with nicotine and alcohol abuse resulting in comorbidities
      like liver cirrhosis and reduced pulmonary function; in contrast, AEG I is
      associated with a high socioeconomic level and cardiovascular risk factors. The
      median age of patients with SCC is 10 years younger than with AEG I. The
      localization of AEG I is in 94% below the tracheal bifurcation, whereas SCC has
      contact to the tracheal bronchial tree in 75%. Furthermore, SCC shows an earlier
      lymphatic spread and a worse prognosis compared to AEG I. The different
      localization and different comorbidities require different therapeutic
      strategies. The preoperative induction therapy consists of combined
      chemoradiotherapy for locally advanced SCC and of chemotherapy for AEG I in our
      department. Due to the favorable position of AEG I a classic Ivor-Lewis procedure
      ending with an intrathoracic anastomosis is possible, in contrast, SCC frequently
      requires a subtotal esophagectomy with cervical anastomosis (in a two step
      strategy). Therefore, at the moment there is no doubt that SCC and AEG I are two
      different diseases with different pathogenesis, epidemiology, tumor biology and
      prognosis requiring different therapeutic strategies. We suggest that the two
      different tumor entities should be analyzed and reported separately to provide
      comparable results in the future.

PMID- 17185197
TI  - Preoperative chemoradiation for the treatment of locoregional esophageal cancer:
      the standard of care?
AB  - Esophageal cancer has one of the highest mortality rates among patients with
      solid tumors. Surgical resection has been a cornerstone of treatment for
      localized esophageal cancer, but recently treatment strategies have become more
      aggressive and now include chemotherapy, radiation, and surgery. Two meta
      analyses confirmed a survival benefit at 3 years from neoadjuvant concurrent
      chemoradiation without compromising the ability to undergo surgical resection and
      without an increase in peri-operative mortality negating the benefit seen. Some
      countries prefer to use pre-operative chemotherapy, although this is not standard
      in the United States. Patients who undergo initial esophagectomy with no pre
      operative treatment may benefit from post-operative adjuvant chemoradiation
      depending on the final pathologic staging. Ultimately, treatment planning should
      include a multi-disciplinary evaluation of the patient, with consideration of
      available treatment options and their risks and benefits. There is no absolute
      standard that is best for all patients; rather, the physician and patient working
      in concert eventually determine which of several reasonable treatment options is
      best suited for that individual patient.

PMID- 17185198
TI  - Considerations in treatment planning for esophageal cancer.
AB  - Radiation therapy is an important component of the multidisciplinary management
      of esophageal cancer. In this article, we review the current approaches to
      achieving the desired dose to the esophagus and regional lymph nodes, with an
      emphasis on the dose constraints to adjacent normal structures, particularly the
      heart and lungs. The application of newer technologies such as positron-emission
      tomography/computed tomography scanning and intensity-modulated radiation therapy
      is also explored.

PMID- 17185199
TI  - Targeted agents and esophageal cancer--the next step?
AB  - Esophageal cancer (EC) is an aggressive cancer and is a leading cause of cancer
      related death worldwide. In the United States and Western Europe, there has been
      a decline in the incidence of squamous cell carcinomas coupled with a rapid rise
      in incidence of adenocarcinoma of the esophagus and gastroesophageal junction.
      Although the 5-year survival rates have slowly increased over time from 4% to
      14%, the outcomes are still dismal. The lack of adequate preventative strategies,
      inadequate screening techniques, early lymphatic and hematogenous spread, and
      lack of truly effective therapeutic agents all contribute to the poor outcome.
      This review will highlight the current status of targeted therapies in EC. This
      will include a review of agents targeting the vascular endothelial growth factor
      and epidermal growth factor receptor pathways and trials planned or ongoing to
      incorporate these and other agents into therapy for advanced disease and into
      combined modality therapy for early-stage tumors. Further work is required
      regarding the rational integration of these targeted agents and the optimal
      selection of patients who will most likely benefit.

PMID- 17185200
TI  - Long-acting hormonal contraceptives--indispensable in preventing teen pregnancy.

PMID- 17185201
TI  - Predictors of adolescent sexual behavior and intention: a theory-guided
      systematic review.
AB  - PURPOSE: To better understand why adolescents initiate sexual activity at early
      ages, we conducted a systematic literature review guided by eight key elements
      outlined in an integrative theoretical framework. METHODS: Using the matrix
      method for literature reviews, we extracted-from 69 published studies
      statistically significant and nonsignificant findings (related to the attempted
      prediction/explanation of adolescents' sexual behavior and intention) and
      organized them using the various integrative model elements. We also assessed
      these publications' methodological quality including each study's deployment of
      theory, appropriate design, and data analytic/reporting techniques. RESULTS:
      Three integrative theoretical framework elements-intention, perceived norms, and
      an environmental constraint variable, time home alone-emerged as stable
      predictors of sexual behavior outcomes in this body of literature. This analysis
      revealed, however, a literature that has remained rather stagnant regarding its
      methodological quality, over time. CONCLUSIONS: Implications for adolescent
      sexual health promotion practice and research are discussed.

PMID- 17185202
TI  - Depo Now: preventing unintended pregnancies among adolescents and young adults.
AB  - PURPOSE: We compared the immediate administration of DMPA (Depo Now) to the
      immediate use of short-term hormonal methods that served as a "bridge method"
      until later DMPA initiation. We examined whether Depo Now, as compared to
      initiating with a bridge method (pills, transdermal patch, or vaginal ring),
      resulted in greater DMPA continuation at six months. METHODS: Young women aged 14
      to 26 years seeking to use DMPA were randomized (nonblinded) after meeting
      eligibility criteria to either the Depo Now (n = 101) or bridge method (n = 232)
      group. Depo Now subjects received their first injection of DMPA at the conclusion
      of their first visit provided each was medically suitable and had a negative
      urine pregnancy test regardless of menstrual cycle day. Those assigned to the
      bridge method group were allowed to choose their starting contraceptive method
      and it was provided at the first visit. All subjects were told to return to the
      clinic in 21 days to repeat the urine pregnancy test, and among those who were
      assigned to use a bridge method, to receive their first injection of DMPA. All
      subjects were followed to their third injection, or about 6 months later.
      RESULTS: Those randomized to a bridge method were 1.8 (1.1, 2.9) times more
      likely than Depo Now subjects to return for their 21-day repeat pregnancy test,
      but only 55% (n = 125) of these young women actually received their first DMPA
      injection. Continuation rates at the third injection were 29.7% (n = 30) for
      those in the Depo Now group and 21.1% (n = 49) for those assigned to the bridge
      method (p = .09). Three factors were significantly associated with adherence to
      the third injection: randomized to Depo Now group, knowing more women who use
      DMPA, and returning to clinic for the 21-day repeat pregnancy test visit.
      Finally, 28 pregnancies were diagnosed during the study period, and those in the
      bridge method group were almost 4.0 (1.2, 13.4) times more likely to be diagnosed
      with a pregnancy than those in the Depo Now group. CONCLUSIONS: Immediate
      administration of DMPA is associated with improved adherence to DMPA continuation
      and fewer pregnancies.

PMID- 17185203
TI  - Effect of type 1 diabetes on psychosocial maturation in young adults.
AB  - PURPOSE: Previous research suggests that having diabetes may complicate the
      passage from adolescence to adulthood. The aim of this study was to establish if
      young adults with Type 1 diabetes (T1DM) had delays in aspects of their
      psychosocial maturation compared with healthy controls (HC). METHODS: A cross
      sectional study compared psychosocial maturation in individuals aged 18-25 years
      with T1DM to age-matched healthy controls. After obtaining consent, participants
      completed the following measures: Responsibility and Independence Scale for
      Adolescents (RISA; psychosocial maturity); Social Maturation Index (SMI, social
      maturity); Levenson's Locus of Control Scales (LOC, internal versus external
      locus of control) and the Social Density Grid (SDG, social network). RESULTS: In
      total, 160 subjects completed the study (97 T1DM, 63 HC). Participants included
      101 females. No group differences were found on the RISA total score or the
      Responsibility or Independence Subscales of this measure. On the SMI, the
      proportion of subjects within each category (good, moderate or poor) was similar
      for each group. The overall number of social contacts identified on the SDG was
      similar for all groups; however, individuals with diabetes identified fewer
      friends within their social network that knew each other (F (2,160) = 3.28, p <
      .05). No significant group differences were found for LOC. CONCLUSIONS: Young
      adults with Type 1 diabetes did not show delayed psychosocial maturation when
      compared with healthy young adult controls.

PMID- 17185204
TI  - The role of friendship in the lives of male and female adolescents: does diabetes
      make a difference?
AB  - PURPOSE: We examined differences in the nature of friendship between adolescents
      with diabetes and healthy adolescents. We also examined whether friend support
      and negative relations with friends were related to health for both groups.
      METHOD: We interviewed 127 adolescents with diabetes and 129 healthy adolescents
      on two occasions, separated by one year. We measured aspects of friendship and
      psychological health among both groups as well as self-care behavior and
      metabolic control among adolescents with diabetes. We used logistic regression
      analysis to predict the presence of friends, repeated measures analysis of
      covariance to predict changes in friendship over time, and hierarchical multiple
      regression analysis to examine the relations of friendship to psychological
      health, self-care behavior, and metabolic control. RESULTS: Both groups of
      adolescents were equally likely to have a best friend and boyfriend/girlfriend,
      but healthy adolescents were more likely to have an other-gender friend.
      Adolescents with diabetes and healthy adolescents reported similar levels of
      friend support, but support increased over the year for healthy girls only. Boys
      with diabetes had the lowest levels of friend support. Negative relations with
      friends were inversely related to psychological health and predicted a decline in
      psychological health over time. Negative relations also predicted poor metabolic
      control and a deterioration of metabolic control over time. CONCLUSION: There are
      similarities and differences in the nature of friendship for adolescents with
      diabetes compared with healthy adolescents. Friendship serves a protective
      function for psychological health for both groups and has implications for
      physical health among those with diabetes.

PMID- 17185205
TI  - Bone mineral density in postmenarchal adolescent girls in the United States:
      associated biopsychosocial variables and bone turnover markers.
AB  - PURPOSE: During adolescence, bone formation prevails over resorption, resulting
      in accumulation of 40% of peak bone mass throughout this time period. Although
      multiple studies have explored bone mass accrual during the early stages of
      puberty, less is known about factors that may influence bone accrual during later
      years of adolescence. In the present cross-sectional study we examined
      relationships among bone mineral density (BMD) and demographic factors,
      behavioral variables, and bone metabolism markers in postmenarchal adolescent
      girls. METHODS: The population was comprised of 389 healthy postmenarchal
      adolescent girls aged 11-18 years, who were recruited into a prospective study of
      the effect of depot medroxyprogesterone acetate (DMPA) on bone health in
      adolescents. At the baseline visit, investigators collected demographic,
      reproductive health, and lifestyle data, and performed a complete physical
      examination. Body mass index (BMI) was calculated. Before study initiation, BMD
      at the lumbar spine, total hip, and femoral neck was measured by dual-energy X
      ray absorptiometry (DXA), and markers of bone metabolism (serum bone-specific
      alkaline phosphatase [BAP], serum osteocalcin, and urinary N-telopeptide [uNTX])
      were measured. The baseline data from this study were analyzed to evaluate
      possible correlates of BMD in postmenarchal adolescent girls. Potential
      associations between BMD values and other parameters were assessed by analysis of
      variance and Pearson's correlation coefficient. RESULTS: Participants enrolled in
      the study had a mean (+/- SD) chronological age of 14.9 +/-1.7 years (range 11
      18), mean gynecologic age of 39.9 +/-23.0 months (range 1-120) postmenarche, and
      mean BMI of 23.5 +/-4.6 kg/m(2) (range 16.0-42.2). Racial/ethnic distribution was
      46% African American, 35% Caucasian, and 19% other races; 9% had previously been
      pregnant. Positive correlations were observed between lumbar spine BMD and
      chronological age (r = .301, p < .0001), gynecologic age (r = .349, p < .0001),
      and BMI (r = .371, p < .0001). Total hip and femoral neck BMD values were
      significantly higher (p < .05 and p < .05, respectively) in African American
      participants compared with non-African American participants. Previous history of
      pregnancy was significantly associated with a lower BMD at the lumbar spine (p <
      .0001) and the total hip (p < .01) when compared with the BMD of adolescents who
      had never been pregnant. Cigarette smoking and alcohol use were not associated
      with significant differences in BMD. Negative correlations were observed between
      gynecologic age and the levels of BAP (r = -.564, p < .0001), osteocalcin (r = 
      .349, p < .0001), and uNTX (r = -.281, p < .0001), and between lumbar spine BMD
      and BAP (r = -.363, p < .0001), osteocalcin (r = -.129, p < .05), and uNTX (r = 
      .202, p < .001) levels. CONCLUSIONS: Our data demonstrate that chronological age,
      gynecologic age, race/ethnicity, BMI, and previous history of pregnancy are
      markedly associated with BMD in postmenarchal adolescent girls. Bone accretion in
      the postmenarchal years continues in the face of a slowdown in bone turnover
      during this time period.

PMID- 17185206
TI  - Smoking topography in response to denicotinized and high-yield nicotine
      cigarettes in adolescent smokers.
AB  - PURPOSE: The objective of this study was to explore the smoking topography of
      adolescent smokers. It is well established that the majority of adult nicotine
      dependent smokers began smoking as adolescents. Whereas recent advances have been
      made with respect to identification of factors that predispose to nicotine
      dependence, very little is known about the actual smoking behavior (e.g.,
      topography) of adolescent smokers, or its relationship to nicotine dependence.
      Correspondingly, the extent to which adolescent smokers smoke to obtain nicotine
      is also unknown. METHODS: In the present study, we assessed several topographical
      indices of smoking (e.g., puff volume, puff number) in a sample of 35 light,
      adolescent smokers. Moreover, we examined whether smoking behavior is different
      in response to smoking a denicotinized relative to a high-yield, nicotine
      cigarette. RESULTS: All participants evidenced a significant increase in expired
      air carbon monoxide after the smoking of a cigarette. Results of independent
      sample t-tests revealed that adolescents who smoked a low-yield nicotine
      cigarette took significantly more puffs per cigarette than did those who smoked a
      high-yield cigarette. CONCLUSIONS: These findings suggest that adolescent smokers
      do titrate their nicotine intake in response to smoking denicotinized cigarettes,
      but do so not by taking larger puffs or smoking more quickly, but by simply
      taking more puffs per cigarette. Implications of the findings and future
      directions for this type of research with adolescents are discussed.

PMID- 17185207
TI  - Costs and cost-effectiveness of adolescent compliance with treatment for latent
      tuberculosis infection: results from a randomized trial.
AB  - PURPOSE: Assess the costs and cost-effectiveness of an incentive-based
      tuberculosis (TB) program designed to promote adolescents' compliance with
      treatment for latent TB infection (LTBI). METHODS: Randomized controlled trial.
      Adolescents between the ages of 11 and 19 years who were referred to one of two
      participating clinics after being screened for TB and receiving a positive
      diagnosis indicating LTBI (n = 794) were assigned to one of four groups: usual
      care, peer counseling, contingency contracting, and combined peer
      counseling/contingency contracting. Primary outcome variables were completion of
      isoniazid preventive therapy (IPT), total treatment costs, and lifetime TB
      related costs per quality-adjusted life year (QALY) in each of the four study
      groups (three treatment, one control). Cost effectiveness was evaluated using a
      five-stage Markov model and a Monte Carlo simulation with 10,000 trials. RESULTS:
      Average costs were 199 dollars for usual care (UC), 277 dollars for peer
      counseling (PC), 326 dollars for contingency contracting (CC), and 341 dollars
      for PC + CC combined. The differences among these groups were all significant at
      the p = .001 level. Only the PC + CC group improved the rate of IPT completion
      (83.8%) relative to usual care (75.9%) (p = .051), with an overall incremental CE
      ratio of 209 dollars per QALY relative to usual care. CONCLUSION: Incentives
      combined with peer counseling are a cost-effective strategy for helping
      adolescents to complete care when combined with peer counseling.

PMID- 17185208
TI  - Fertility issues: the perceptions and experiences of young men recently diagnosed
      and treated for cancer.
AB  - PURPOSE: To explore fertility issues for young men who had been diagnosed and
      treated for cancer and to examine communication problems surrounding these
      fertility issues. METHOD: Narrative interviews were conducted with 21 young men
      previously treated for cancer in the United Kingdom. Eighteen talked about
      fertility issues at some length. A qualitative interpretive approach was taken,
      combining thematic analysis with constant comparison. RESULTS: Communication
      about sperm storage was sometimes difficult and embarrassing. Young men wanted
      the opportunity to bank their sperm but decisions were often rushed. Some would
      have appreciated counseling and were unprepared for the process of sperm banking
      and criticized facilities. Uncertainty about fertility status caused worries for
      the future. CONCLUSIONS: More still needs to be done to help young men with
      cancer to address issues of fertility. All adolescents and young men treated for
      cancer should be offered sperm banking if their fertility may be affected. They
      should be offered counseling at every stage by professionals who feel comfortable
      talking about the subject. Interactive, educational CD-ROMs or websites may be
      useful. Physical facilities for sperm banking should be improved.

PMID- 17185210
TI  - Female conduct disorder: health status in young adulthood.
AB  - PURPOSE: One of the risk factors for poor adult health may be adolescent
      antisocial behavior, especially in girls. This study was conducted to determine
      if negative young adult health outcomes in girls who previously had adolescent
      antisocial behavior could be explained by demographic factors and pre-existing
      health problems. METHODS: This 3-year longitudinal study recruited 93 girls, ages
      15-17 years (52 with conduct disorder [CD]; 41 with no psychiatric illness
      [normal controls; NC]) from the community. Baseline interviews of girls and
      parents collected demographic, psychiatric, and medical history data. Three
      annual interviews collected data about medical problems, health care service
      utilization, and reproductive health. In addition, the final follow-up included a
      standardized self-report questionnaire about young adult health status. RESULTS:
      CD and NC groups did not differ in age, racial composition, social class,
      proportion of smokers, or drug and alcohol experimentation. They were
      qualitatively different in baseline medical histories. Controlling for age at
      follow-up and baseline medical problems, the CD group as young adults had worse
      overall health, more discomfort, higher rates of unhealthy habits, lower rates of
      healthy behaviors, and more pregnancies at earlier ages. There were no group
      differences in rates of disorders, injuries, or health care usage. CONCLUSIONS:
      Adolescent girls with CD as young adults have poorer overall health, more
      discomfort, more health risk behaviors, and earlier onset of adult reproductive
      behaviors, even when controlling for demographic factors and pre-existing health
      history. Clinical and research implications are discussed.

PMID- 17185209
TI  - Medical and nonmedical use of prescription drugs among secondary school students.
AB  - PURPOSE: The main objective of this study was to assess the prevalence of medical
      and nonmedical use of four categories of prescription drugs (opioid, stimulant,
      sleeping, and sedative/anxiety medication) in a racially diverse sample of
      secondary public school students in the Detroit metropolitan area. A secondary
      objective was to examine the association between the use of four categories of
      prescription medications and illicit drug use and probable drug abuse. METHODS:
      In 2005, a Web-based survey was self-administered by 1086 secondary school
      students in grades seven through 12. RESULTS: The sample consisted of 54% female,
      52% White, 45% African American, and 3% from other racial categories. Forty-eight
      percent of the sample reported no lifetime use of four categories of prescription
      drugs (nonusers), 31.5% reported medically prescribed use only (medical users),
      17.5% reported both medical and nonmedical use (medical/nonmedical users) and
      3.3% reported nonmedical use only (nonmedical users). Multivariate analyses
      indicated that medical/nonmedical users and nonmedical users were significantly
      more likely than nonusers to report illicit drug use and probable drug abuse.
      Medical users generally reported similar or increased odds of illicit drug use
      and probable drug abuse than non-users. CONCLUSIONS: These findings provide
      evidence that nonmedical use of prescription drugs represents a problem behavior
      among secondary school students.

PMID- 17185212
TI  - Relationship of condom use with other sexual risk behaviors among selected
      Japanese adolescents.
AB  - This study examines relationships between condom use and age at initiation of
      sex, the number of sexual partners, and alcohol or drug use before sex among a
      convenience sample of 2852 Japanese adolescents. We found that nonuse of condoms
      is related to early initiation of sex, having multiple sexual partners and
      alcohol or drug use before sex.

PMID- 17185211
TI  - Rethinking the associations between television viewing and adolescent sexuality
      development: bringing gender into focus.
AB  - PURPOSE: To investigate associations between adolescents' television viewing,
      their sexual behavior, and their perceptions of having power and control in
      sexual situations (i.e., sexual agency). This study incorporates results from a
      recent content analysis of television and attends to the different motives for
      and consequences of girls' and boys' sexual and relational behavior. METHODS:
      Adolescents (n = 703) aged 11 to 17 years from two public school districts in the
      Northeastern United States completed surveys assessing their television habits
      and sexual experiences. Survey data were combined with two content analyses,
      which assessed the frequency of sexual talk and behavior and the prevalence of
      gendered messages about sexuality (i.e., the Heterosexual Script) on primetime
      network television. RESULTS: Adolescents' sexual behavior and feelings of sexual
      agency were not associated with viewing sexual talk and sexual behavior on
      television, but were related to viewing the Heterosexual Script, particularly
      among girls. Girls who saw sexually objectified women and portrayals of men
      avoiding commitment more often reported less sexual agency. Girls who saw women
      acting as sexual gatekeepers more often were less sexually experienced and
      reported more sexual agency. Boys who saw men actively asserting their sexuality
      more often were less sexually experienced. CONCLUSIONS: The relationship between
      adolescents' television viewing and sexual experiences depends on the type of
      sexual messages viewed, the sexual outcome considered, and the gender of the
      viewer. Parents and practitioners should learn to identify the Heterosexual
      Script on television and encourage young people to negotiate sexual encounters in
      safe and positive ways.

PMID- 17185213
TI  - A retrospective examination of the relationship between body mass index and
      polysomnographic measures of sleep in adolescents.
AB  - Total sleep time is inversely related to body mass index (BMI) in adults and
      children, an observation not well characterized in the adolescent population. We
      conducted a retrospective chart review that indicated certain sleep disruptions
      were associated with increased BMI by polysomnography in this group.

PMID- 17185214
TI  - Provision of emergency contraceptive pills at college and university student
      health centers in Florida.
AB  - Provision of emergency contraceptive (EC) pills at Florida university and college
      student health centers was examined. Practices related to dosages, pill brands,
      advance prescriptions, restrictions, written policy, printed materials, routine
      contraceptive counseling, and publicity were identified. Barriers for centers not
      providing EC pills and practices were also determined.

PMID- 17185215
TI  - Stigma scale revised: reliability and validity of a brief measure of stigma for
      HIV+ youth.
AB  - The purpose of this study was to shorten a human immunodeficiency virus (HIV)
      stigma scale to make it less burdensome for HIV-positive (HIV+) youth without
      compromising psychometric properties. The shortened questionnaire showed good
      internal consistency and validity, suggesting that a 10-item measure of stigma
      has promise for assessing this important construct in HIV+ youth.

PMID- 17185217
TI  - Correspondence letter in response to Kincl et al manuscript.

PMID- 17185218
TI  - Ablynx makes nanobodies from llama bodies.

PMID- 17185219
TI  - No need to be pure: mix the cultures!
AB  - In this issue of Chemistry & Biology, Angell et al. demonstrate synergism between
      two bacterial species, isolated from the same sediment sample, to produce a
      secondary metabolite not found in their respective pure cultures.

PMID- 17185220
TI  - Beta strand peptidomimetics as potent PDZ domain ligands.
AB  - The search for general strategies for inhibiting protein-protein interactions has
      been stimulated by recognition of the key role they play in virtually every
      process of living systems. Multiprotein complex assembly and localization by PDZ
      domain-containing proteins exemplify processes critical to cell physiology and
      function that are mediated by beta strand association. Here we describe the
      development of substituted "@-tides," protease-resistant peptidomimetics
      incorporating conformationally restricted amino acid surrogates that reproduce
      the hydrogen-bonding pattern and side-chain functionality of a beta strand. The
      synthetic flexibility and generality of the substituted @-tide design was
      demonstrated by the synthesis of a panel of ligands for the alpha1-syntrophin PDZ
      domain. The rational design of a small molecule of unprecedented affinity for the
      PDZ domain suggests that these peptidomimetics may provide a general method for
      inhibiting protein-protein interactions involving extended peptide chains.

PMID- 17185221
TI  - Metabolic engineering of Pseudomonas putida for methylmalonyl-CoA biosynthesis to
      enable complex heterologous secondary metabolite formation.
AB  - An operon consisting of three open reading frames, annotated in silico as
      methylmalonyl-CoA (mm-CoA) epimerase, mm-CoA mutase (MCM), and meaB, was
      identified in the sequencing project of the myxobacterium Sorangium cellulosum So
      ce56. This putative MCM pathway operon was subcloned from a bacterial artificial
      chromosome by Red/ET recombineering onto a minimal replicon derived from p15A.
      This plasmid was modified for integration and heterologous expression in
      Pseudomonas putida to enable the production of complex secondary metabolites
      requiring mm-CoA as precursor. Methylmalonate was identified in the recombinant
      P. putida strain by an analysis method based on gas chromatography/mass
      spectrometry. The engineered strain is able to synthesize polyketides requiring
      mm-CoA as an extender unit, which was demonstrated by the production of
      myxothiazol after integration of the biosynthetic gene cluster into the
      chromosome, followed by induction of expression.

PMID- 17185222
TI  - Targeting glycosylation pathways and the cell cycle: sugar-dependent activity of
      butyrate-carbohydrate cancer prodrugs.
AB  - Short-chain fatty acid (SCFA)-carbohydrate hybrid molecules that target both
      histone deacetylation and glycosylation pathways to achieve sugar-dependent
      activity against cancer cells are described in this article. Specifically, n
      butyrate esters of N-acetyl-D-mannosamine (But4ManNAc, 1) induced apoptosis,
      whereas corresponding N-acetyl-D-glucosamine (But4GlcNAc, 2), D-mannose (But5Man,
      3), or glycerol (tributryin, 4) derivatives only provided transient cell cycle
      arrest. Western blots, reporter gene assays, and cell cycle analysis established
      that n-butyrate, when delivered to cells via any carbohydrate scaffold,
      functioned as a histone deacetylase inhibitor (HDACi), upregulated p21WAF1/Cip1
      expression, and inhibited proliferation. However, only 1, a compound that primed
      sialic acid biosynthesis and modulated the expression of a different set of genes
      compared to 3, ultimately killed the cells. These results demonstrate that the
      biological activity of butyrate can be tuned by sugars to improve its anticancer
      properties.

PMID- 17185223
TI  - Analysis of the ambruticin and jerangolid gene clusters of Sorangium cellulosum
      reveals unusual mechanisms of polyketide biosynthesis.
AB  - Ambruticins and jerangolids are structurally related antifungal polyketides
      produced by Sorangium cellulosum strains. Comparative analysis of the gene
      clusters and characterization of compounds produced by gene knockout strains
      suggested hypothetical schemes for biosynthesis of these compounds. Polyketide
      synthase (PKS) architecture suggests that the pyran ring structure common to
      ambruticins and jerangolids forms by an intramolecular reaction on a PKS-bound
      intermediate. Disrupting ambM, encoding a discrete enzyme homologous to PKS C
      methyltransferase domains, gave 15-desmethylambruticins. Thus, AmbM is required
      for C-methylation, but not pyran ring formation. Several steps in the post-PKS
      modification of ambruticin involve new enzymology. Remarkably, the
      methylcyclopropane ring and putative carbon atom excision during ambruticin
      biosynthesis apparently occur on the PKS assembly line. The mechanism probably
      involves a Favorskii rearrangement, but further work is required to elucidate
      these complex events.

PMID- 17185224
TI  - RNA-mediated sequestration of the RNA helicase eIF4A by Pateamine A inhibits
      translation initiation.
AB  - Eukaryotic initiation factor 4A (eIF4A) is a member of the DEAD-box family of
      putative RNA helicases whose members are involved in many aspects of RNA
      metabolism. eIF4A is thought to facilitate binding of 43S preinitiation complexes
      to mRNAs by unwinding secondary structures present in the 5' untranslated region.
      Pateamine A, a small-molecule inhibitor of translation initiation, acts in an
      unusual manner by stimulating eIF4A activity. Herein, we report the elucidation
      of pateamine's mode of action. We demonstrate that Pateamine A is a chemical
      inducer of dimerization that forces an engagement between eIF4A and RNA and
      prevents eIF4A from participating in the ribosome-recruitment step of translation
      initiation.

PMID- 17185226
TI  - Structural and antitumor properties of the YSNSG cyclopeptide derived from
      tumstatin.
AB  - We previously demonstrated that the NC1[alpha3(IV)185-191] CNYYSNS peptide
      inhibited in vivo tumor progression. The YSNS motif formed a beta turn crucial
      for biological activity. The aim of the present study was to design a YSNSG
      cyclopeptide with a constrained beta turn on the YSNS residues more stable than
      CNYYSNS. By nuclear magnetic resonance and molecular modeling, we demonstrated
      that the YSNSG cyclopeptide actually adopted the expected beta-turn conformation.
      It promoted melanoma cell adhesion and prevented their adhesion to the native
      peptide. It inhibited in vitro cell proliferation and migration through Matrigel
      by downregulating proteolytic cascades. Moreover, intraperitoneal administration
      of the YSNSG cyclopeptide inhibited melanoma progression far more efficiently
      than the native peptide. The increased solubility and stability at low pH of the
      YSNSG cyclopeptide suggest this peptide as a potent antitumor therapeutic agent.

PMID- 17185225
TI  - Structural and molecular evolutionary analysis of Agouti and Agouti-related
      proteins.
AB  - Agouti (ASIP) and Agouti-related protein (AgRP) are endogenous antagonists of
      melanocortin receptors that play critical roles in the regulation of pigmentation
      and energy balance, respectively, and which arose from a common ancestral gene
      early in vertebrate evolution. The N-terminal domain of ASIP facilitates
      antagonism by binding to an accessory receptor, but here we show that the N
      terminal domain of AgRP has the opposite effect and acts as a prodomain that
      negatively regulates antagonist function. Computational analysis reveals similar
      patterns of evolutionary constraint in the ASIP and AgRP C-terminal domains, but
      fundamental differences between the N-terminal domains. These studies shed light
      on the relationships between regulation of pigmentation and body weight, and they
      illustrate how evolutionary structure function analysis can reveal both unique
      and common mechanisms of action for paralogous gene products.

PMID- 17185227
TI  - Discovery of a substrate selectivity switch in tyrosine ammonia-lyase, a member
      of the aromatic amino acid lyase family.
AB  - Tyrosine ammonia-lyase (TAL) is a recently described member of the aromatic amino
      acid lyase family, which also includes phenylalanine (PAL) and histidine ammonia
      lyases (HAL). TAL is highly selective for L-tyrosine, and synthesizes 4-coumaric
      acid as a protein cofactor or antibiotic precursor in microorganisms. In this
      report, we identify a single active site residue important for substrate
      selection in this enzyme family. Replacing the active site residue His89 with Phe
      in TAL completely switched its substrate selectivity from tyrosine to
      phenylalanine, thereby converting it into a highly active PAL. When a
      corresponding mutation was made in PAL, the enzyme lost PAL activity and gained
      TAL activity. The discovered substrate selectivity switch is a rare example of a
      complete alteration of substrate specificity by a single point mutation. We also
      show that the identity of the amino acid at the switch position can serve as a
      guide to predict substrate specificities of annotated aromatic amino acid lyases
      in genome sequences.

PMID- 17185228
TI  - Structural determinants and modulation of substrate specificity in phenylalanine
      tyrosine ammonia-lyases.
AB  - Aromatic amino acid ammonia-lyases catalyze the deamination of L-His, L-Phe, and
      L-Tyr, yielding ammonia plus aryl acids bearing an alpha,beta-unsaturated
      propenoic acid. We report crystallographic analyses of unliganded Rhodobacter
      sphaeroides tyrosine ammonia-lyase (RsTAL) and RsTAL bound to p-coumarate and
      caffeate. His 89 of RsTAL forms a hydrogen bond with the p-hydroxyl moieties of
      coumarate and caffeate. His 89 is conserved in TALs but replaced in phenylalanine
      ammonia-lyases (PALs) and histidine ammonia-lyases (HALs). Substitution of His 89
      by Phe, a characteristic residue of PALs, yields a mutant with a switch in
      kinetic preference from L-Tyr to L-Phe. Structures of the H89F mutant in complex
      with the PAL product, cinnamate, or the PAL-specific inhibitor, 2-aminoindan-2
      phosphonate (AIP), support the role of position 89 as a specificity determinant
      in the family of aromatic amino acid ammonia-lyases and aminomutases responsible
      for beta-amino acid biosynthesis.

PMID- 17185231
TI  - [Should we still prescribe a low protein diet in chronic kidney disease?].

PMID- 17185230
TI  - Pyocyanin isolated from a marine microbial population: synergistic production
      between two distinct bacterial species and mode of action.
AB  - Marine microbial populations collected from the Hawaiian Islands were screened
      for antimicrobial activity. A blue metabolite was identified from mixed cell
      cultures, but production was not evident in pure cultures. Experiments designed
      to probe the synergistic role of the microorganisms are presented. Full
      characterization of the blue natural product, pyocyanin, is provided including
      corrections made to 1H and 13C-NMR assignments of the molecule misreported in the
      chemical literature and yeast transcriptome analysis. The transcriptional effects
      were consistent with the compound's purported role as an inducer of oxidative
      stress and damage and illustrates the overall potential of the method to reveal
      the primary biological/cellular effects of a natural product. The experiments
      outlined here might serve as a general paradigm for identification of natural
      products arising from microbial communities and investigation of their respective
      interactions.

PMID- 17185229
TI  - An inhibitor of human asparagine synthetase suppresses proliferation of an L
      asparaginase-resistant leukemia cell line.
AB  - Drug resistance in lymphoblastic and myeloblastic leukemia cells is poorly
      understood, with several lines of evidence suggesting that resistance can be
      correlated with upregulation of human asparagine synthetase (hASNS) expression,
      although this hypothesis is controversial. New tools are needed to investigate
      this clinically important question, including potent hASNS inhibitors. In vitro
      experiments show an adenylated sulfoximine to be a slow-onset, tight-binding
      inhibitor of hASNS with nanomolar affinity. This binding affinity represents a 10
      fold improvement over that reported for the only other well-characterized hASNS
      inhibitor. The adenylated sulfoximine has a cytostatic effect on L-asparaginase
      resistant MOLT-4 cells cultured in the presence of L-asparaginase, an enzyme that
      depletes L-asparagine in the growth medium. These observations represent direct
      evidence that potent hASNS inhibitors may prove to be effective agents for the
      clinical treatment of acute lymphoblastic leukemia.

PMID- 17185232
TI  - [Microbial nucleic acids in the pathogenesis of glomerulonephritis].
AB  - Recent advances in the understanding of innate pathogen recognition revealed that
      nucleic acids have immunomodulatory functions in inflammation. A set of Toll-like
      pattern-recognition receptors recognize various types of microbial nucleic acids,
      i.e. double-stranded viral RNA (TLR3), single-stranded viral RNA (TLR7 and TLR8),
      and viral and bacterial CpG-DNA (TLR9). All of these TLRs are differentially
      expressed in the healthy and diseased kidney and TLR ligation was shown to
      initiate and modulate experimental glomerulonephritis. In this review we
      summarize the arising evidence in this field and discuss new hypotheses for the
      pathogenesis of kidney diseases that are triggered by infectious organisms.

PMID- 17185233
TI  - Position statement regarding usage of biosimilars: position paper of the Societe
      de nephrologie, Societe francophone de dialyse, and Societe de nephrologie
      pediatrique.

PMID- 17185234
TI  - [Dental problems and their management in uraemic patients].
AB  - Bad dental status is very often observed in hemodialyzed patients due to the fact
      of a frequent poor oral hygiene and, in addition of the traditional risk factors,
      the consequences of uraemic state and its treatment. However , among such
      immunodepressed patients, oral and dental lesions represent a risk of septic
      complications. Moreover some works point out the prevalence of inflammation and
      denutrition due to dental lesions in the uraemic population, with potential
      atherosclerosis. Therefore, in order to anticipate all these adverse effects and
      to restore their mouth to health, patients have to be encouraged to have
      regularly a full dental evaluation and correction if not elimination of all
      potential sources of infection and other complications. To ensure the best
      treatment, a close collaboration has to be established with dental practitioners
      who must be aware and convinced of the complexity of such patients:
      immunodepression due to uraemic state and sometimes to drug therapy; importance
      of prophylactic antibiotic therapy surrounding dental cares; cautions to
      hemostasis circumstances; adjusted use of some medications. To illustrate this
      matter, we report here a study involving 96 hemodialyzed patients who were
      investigated by panoramic radiography and clinical cross- examination about their
      dental complaints and habits. We then expose our practices and detail our
      collaboration with their dentists in establishing a plan of dental treatment.

PMID- 17185235
TI  - [Be careful in using flecainide by hemodialyzed patients].
AB  - Cardiac arrhythmias are frequent by hemodialyzed patients and may lead to the
      prescription of antiarrhythmic drugs among which flecainide. However there is for
      this latter a wide interindividual variability in the dose-plasma concentration
      relationship because of a genetically controlled polymorphic metabolism. That
      explains why it is not possible to adjust dose only to renal clearance. It
      becomes even more difficult at hemodialysis stage, especially if hepatic
      insufficiency and/or certain medications join to it. So this antiarrhythmic drug
      has to be cautiously initiated and plasma concentrations have to be carefully
      monitored to avoid side effects, sometimes crippling as in our observation,
      sometimes as cardiac complications.

PMID- 17185236
TI  - [Crescentic glomerulonephritis].
AB  - Crescentic glomerulonephritis are characterised by a crescent shaped cellular
      proliferation that may lead to glomerular destruction. Over 50% of at least 10
      analysed glomeruli should be affected. The search for immune deposits by
      immunofluorescence is an important diagnostic step. Patients present with rapidly
      progressive glomerulonephritis (RPGN): renal failure, proteinuria and haematuria.
      Extra-renal symptoms may help diagnosis. Diseases are classified in three groups
      according to immunofluorescence studies. Group I is characterised by linear
      deposits along the glomerular basement membrane (GBM) with anti-GBM auto
      antibodies responsible for Goodpasture's disease. Group II put together various
      diseases with immune complex deposits. In group III, no significant immune
      deposits are found. Those "pauci-immune" glomerulonephritis are secondary to anti
      neutrophil cytoplasmic antibodies (ANCA) positive systemic vasculitis, mainly
      Wegener's granulomatosis and microscopic polyangiitis. Primary glomerulonephritis
      may also be associated with crescent formation. Treatment is urgently required.
      Diagnosis is suspected in the context of extra-renal symptoms or immunological
      abnormalities, and confirmed by a kidney biopsy, that also helps to define
      prognosis. Apart from some group II glomerulonephritis, the induction treatment
      is often an association of steroids and cyclophosphamide, with plasma exchange in
      case of Goodpasture's disease. After remission, a maintenance treatment is
      required for ANCA-positive vasculitis to prevent relapses. The high rate of
      opportunistic infections and cancer give the rational for searching less
      aggressive therapeutic options.

PMID- 17185237
TI  - Applications of 24-hour noninvasive ambulatory blood pressure monitoring.
AB  - Casual blood pressure (CBP) measurements using a standard sphygmomanometer have
      traditionally constituted the principal modality for the assessment and
      management of hypertension. However, CBP measurement has shortcomings. Ambulatory
      blood pressure monitoring (ABPM) provides abundant information on blood pressure
      (BP), including heart rate, all BP readings for test periods, BP average, BP
      variability, BP load, load index, distribution pattern of BP, reduction
      percentage of BP, trough/peak ratio, and summary statistics for overall 24-hour,
      daytime and nighttime periods. Over the last three decades, ABPM has evolved from
      a research device to an established and valuable clinical tool for assessment and
      management of hypertension. This technology has been proven to be useful in terms
      of the distribution pattern of BP, characterization of BP profiles in
      normotensive and hypertensive patients, evaluation of patients with mild or
      labile hypertension, physiologic and psychologic factors for fluctuation of BP,
      load index study, study of white coat hypertension, etiology of hypertension,
      prognosis of hypertension, and assessment of antihypertensive management.
      Nevertheless, the technology remains underused due to lack of insurance
      reimbursement in most countries. Accordingly, insurance reimbursement is crucial
      to promote increased utility of ABPM. Clinicians should be familiar with the role
      of this technology in the care of patients with abnormal BP. This review is an
      attempt to increase clinicians' understanding of ABPM and the appropriate use of
      this technology.

PMID- 17185238
TI  - Microbial etiology of acute gastroenteritis in hospitalized children in Taiwan.
AB  - BACKGROUND/PURPOSE: Viral infections are the most common causes of acute
      infectious diarrhea in the pediatric population. To explore any possible
      microbial etiologies of acute gastroenteritis in children, we detected stool
      viral antigen including rotavirus, adenovirus, norovirus and astrovirus. We also
      studied the possible precipitating factors. METHODS: During a period of 1 year
      (from October 2003 to September 2004), children from birth to 15 years old
      admitted to the pediatric ward were prospectively surveyed. Stool specimens were
      collected within 48 hours after admission and then frozen at -40 degrees C until
      analysis. Enzyme immunoassay was used to detect rotavirus, astrovirus, norovirus
      and adenovirus. Bacterial culture was performed at the same time. RESULTS: During
      the study period, 82 stool samples were collected due to acute gastroenteritis
      and fit the definition of a diarrhea episode. Forty-two (51.2%) patients with
      viral infection, 11 (13.4%) with bacterial infection, and six (7.3%) with mixed
      viral and bacterial infection were detected. The most prevalent virus was
      rotavirus (35.4%), followed by norovirus (29.3%). The most prevalent cause of
      bacterial infection was Salmonella (19.5%). With regard to clinical severity,
      rotavirus resulted in longer hospital stay, higher rate of vomiting, stool occult
      blood, leukocytosis, lower rate in stool pus cell, and C-reactive protein
      elevation more than 5 mg/dL as compared with norovirus. Only the difference in
      hospital stay reached significant statistical difference. CONCLUSION: Norovirus
      is an important cause of acute gastroenteritis in children, although rotavirus is
      still the leading cause of pediatric acute gastroenteritis.

PMID- 17185239
TI  - Outcome of treatment with total main tumor resection and supraomohyoid neck
      dissection in oral squamous cell carcinoma.
AB  - BACKGROUND/PURPOSE: Supraomohyoid neck dissection (SOHND) is commonly used to
      treat oral squamous cell carcinoma (OSCC) patients with clinical N0 or selected
      N1 status. The purpose of this study was to evaluate the clinical outcome of OSCC
      patients treated with SOHND. METHODS: This retrospective study reviewed the
      clinical outcome of 257 patients (247 men, 10 women) with N0, N1 and N2a OSCC
      treated with wide excision of the main tumor and SOHND between 1992 and 1999. All
      patients were followed up for at least 5 years. Survival distributions were
      analyzed using Kaplan-Meier curves. N status was compared using chi2 and log rank
      tests. RESULTS: The neck failure rate was 20% for clinically false negative
      cases, 6.1% for clinically true negative cases, 21.8% for clinically false
      positive cases, and 40% for clinically true positive cases. The 3- and 5-year
      overall neck disease-free survival rates were 79.8% and 77.6%, respectively. The
      3- and 5-year neck disease-free survival rates were 86.7% and 84.2% for
      pathologic N0 cases, 56.9% and 56.9% for pathologic N1 cases, and 27.5% and 27.5%
      for pathologic N2 cases, respectively. Log rank test showed that the p value for
      difference in survival at 3-5 years was 0.064 for pathologic N0 vs. N1 cases, <
      0.0001 for pathologic N0 vs. N2 cases, and 0.008 for pathologic N1 vs. N2 cases.
      CONCLUSION: This study showed that SOHND is effective for pathologic N0 OSCC,
      relatively effective for pathologic N1, and less effective for pathologic N2a.
      These findings also support that when SOHND is used to treat N2a OSCC,
      postoperative radiotherapy or radical neck dissection may be needed to improve
      the neck disease-free survival rate.

PMID- 17185240
TI  - Patterns and clinical correlates of neuropsychologic deficits in patients with
      schizophrenia.
AB  - BACKGROUND/PURPOSE: Neuropsychologic deficits are prevalent among schizophrenic
      patients and are closely associated with pathogenesis and outcome. The pattern,
      extent, severity and contributing factors to such deficits remain to be examined
      in Taiwanese schizophrenic patients. METHODS: A total of 122 schizophrenic
      patients and 94 healthy subjects for comparison were assessed by a comprehensive
      neuropsychologic test battery covering the eight cognitive domains of verbal
      ability, visual spatial ability, abstraction/execution, verbal memory, visual
      memory, perceptual/motor ability, mental control and attention. The relationships
      among cognitive deficits, demographic characteristics, clinical historical
      variables and clinical symptoms were further explored by multivariate regression
      analysis. RESULTS: A pattern of selective deficits superimposed on a generalized
      deficit was found for schizophrenic patients as a group. The mean overall deficit
      was 1.93 standard deviations below the control mean, and abstraction/execution,
      verbal memory, visual memory and attention were relatively impaired among the
      eight cognitive domains. However, there was also marked heterogeneity in
      individual performances in that 24.2%, 46.2% and 29.5% of patients performed at
      within normal range, moderately impaired and severely impaired levels,
      respectively. Duration of illness substantially affected the profile and severity
      of the deficits, suggesting a progressive deteriorating course in
      neuropsychological performance. The major predictors of cognitive deficits were
      number of formal years of education achieved and concurrent severity of
      disorganization symptoms. CONCLUSION: In a large sample of schizophrenic patients
      who underwent comprehensive neuropsychologic evaluation, the current results
      confirmed that cognitive deficits were prevalent but not a universal feature
      within schizophrenia. The selective impairment pattern also confirmed that such
      deficits were mainly in frontal and frontotemporal related functions. Despite
      evidence suggesting that disease chronicity entailed a decline in selective
      cognitive domains, the trajectory of the neuropsychologic deficits remains to be
      examined by further longitudinal studies.

PMID- 17185241
TI  - Psychometric properties of the Berg Balance Scale in a community-dwelling elderly
      resident population in Taiwan.
AB  - BACKGROUND/PURPOSE: To investigate the psychometric properties (acceptability,
      internal consistency reliability, interrater reliability, construct validity) and
      identify the most challenging items of the Berg Balance Scale (BBS) for elderly
      people living in the community. METHODS: A total of 268 community-dwelling adults
      65 years of age or older volunteered to participate in this study. Each subject's
      performance was assessed with the BBS, timed up and go (TUG) test, and usual gait
      speed. For testing interrater reliability, the other 68 community-dwelling older
      adults who met the criteria were also recruited. RESULTS: The BBS demonstrated
      good internal consistency reliability (Cronbach's alpha = 0.77), good interrater
      reliability (ICC(2,1) = 0.87), and moderate correlation with the TUG and usual
      gait speed (Spearman's rho = -0.53 and 0.46, respectively). The BBS score of the
      mobility/IADL (instrumented activities of daily living) able group was also
      significantly higher than that of the disabled group. Among all items on the BBS,
      tandem stance (item 13) and one-legged stance (item 14) were found to be the most
      challenging items for the subjects in the sample. CONCLUSION: The results of this
      study suggest that the internal consistency reliability, interrater reliability,
      and construct validity of the BBS are adequate for measuring balance in community
      dwelling older adults. Among all items in the BBS, the tandem stance and one
      legged stance are the most challenging items. Further study of their
      applicability for screening use in the community is warranted.

PMID- 17185243
TI  - Primary primitive neuroectodermal tumor of the urinary tract.
AB  - Primary primitive neuroectodermal tumor (PNET) of the urinary tract is a rare
      disease with aggressive behavior and poor prognosis. We analyzed 851 cases of
      urinary tract malignancies in our hospital between 1984 and 2004. Only three
      (0.035%) cases with PNET of the urinary tract were identified. Presenting
      symptoms included flank pain and hematuria. The first case was a 44-year-old man
      with left renal PNET who underwent hand-assisted laparoscopic radical nephrectomy
      and adjuvant chemotherapy. There was no recurrent tumor at the 4-year follow-up.
      The second case was a 75-year-old woman with right renal PNET with inferior vena
      cava (IVC) thrombosis extending to the right atrium. The patient underwent right
      radical nephroureterectomy and IVC thrombectomy with cardiopulmonary bypass. She
      died of metastatic disease 7 months later. The third case was a 45-year-old man
      with left ureteral PNET. Left ureteral segmental resection and partial cystectomy
      were performed. Tumor recurrence was noted 7 years later. The patient died of
      disseminated disease 1 year after the discovery of recurrence. Urinary tract PNET
      appears to be an aggressive malignancy. Long-term survival is possible if
      complete resection is performed at an early stage.

PMID- 17185242
TI  - Cost-effectiveness of different advanced life support providers for victims of
      out-of-hospital cardiac arrests.
AB  - BACKGROUND/PURPOSE: The survival rate of out-of-hospital cardiac arrest (OHCA) is
      only about 1.4% in Taiwan. The best configuration to achieve optimal outcomes in
      OHCA is still uncertain for many communities. The purpose of this study was to
      investigate the cost-effectiveness of two models of providing advanced life
      support (ALS) services, emergency medical technicians (EMTs) vs. emergency
      physicians (EPs), in a two-tiered emergency medical services (EMS) system.
      METHODS: This was a prospective, observational, multicenter study comparing ALS
      provided by EMTs vs. EPs for the management of victims of OHCA. The study
      population consisted of patients experiencing OHCA of non-traumatic origin in
      Taipei city, Taiwan, between November 1999 and December 2000, for whom ALS was
      activated. We performed a cost-effectiveness analysis to determine the economic
      attractiveness of these two ALS provider programs. The outcome measurements were
      aggregate costs, survival and incremental cost per life saved. Sensitivity
      analyses were performed on all variables. RESULTS: The expected total cost per
      OHCA patient was 2,248.19 US$ and 832.07 US$ for the EMT and EP programs,
      respectively. The overall survival rate was 4.4%. The survival rate was 9.3% for
      the EMT program and 2.6% for the EP program. The incremental cost-effectiveness
      ratio (ICER) of EMTs vs. EPs was 21,136 US$ per life saved. The ICER was
      sensitive to hospital admission cost changes and the probability of survival to
      discharge in patients admitted to hospital in the EMT program. The increased
      survival rate of OHCA patients in the EMT program may be attributable to the
      services of the hospital and/or the EMT program. CONCLUSION: The use of EMTs as
      ALS care providers for OHCA patients in the two-tiered EMS system resulted in a
      reasonable cost-effectiveness ratio. EMTs could be considered as the second tier
      of EMS systems in urban areas in Taiwan.

PMID- 17185244
TI  - Novel SOX9 gene mutation in campomelic dysplasia with autosomal sex reversal.
AB  - Campomelic dysplasia (CD; OMIM #114290) is an autosomal dominant, frequently
      lethal dysplasia syndrome whose primary features include angular bowing and
      shortening of the limbs, and sex reversal in the majority of affected XY
      individuals. Most CD cases have heterozygous de novo mutations in the coding
      region of the transcription factor gene SOX9 (SRY-related high-mobility group
      [HMG] box 9) in chromosome 17q. Here, we report a novel mutation of SOX9 in a
      female neonate with CD with autosomal sex reversal. Respiratory distress and
      cyanosis were noted at birth, and endotracheal intubation with mechanical
      ventilation was performed due to respiratory failure. The presenting phenotypes
      included dysmorphic face with macrocephaly, prominent forehead, low nasal bridge,
      cleft palate and micrognathia. Skeletal deformities characteristic of CD were
      observed, including narrow thoracic cage, hypoplastic scapulae, scoliosis and
      short limbs with anterolateral femoral and tibial bowing. The karyotype was 46,XY
      despite female external genitalia. SOX9 gene analysis revealed frameshift
      mutation (at nucleotide position 1095G-->AT) in the open reading frame, resulting
      in a frameshift with 211 new amino acids.

PMID- 17185245
TI  - Adventitial cystic disease.
AB  - Adventitial cystic disease (ACD) is an unusual cystic tumor of blood vessels
      characterized by the accumulation of mucinous substance in the adventitia of the
      non-axial blood vessels adjacent to joints. Patients with ACD often suffer from
      intermittent claudication and/or limb pain, mostly involving the popliteal
      artery. We report a 30-year-old male who presented with intermittent claudication
      in his left leg. Angiography showed an obstructive lesion in the left popliteal
      artery. The lesion was treated successfully by surgical excision followed by
      graft vessel replacement. ACD involving the popliteal artery was diagnosed by
      pathologic findings of multiple cysts of the adventitia with external compression
      and focal narrowing of the vascular lumen. The cysts contained acid mucin and
      were partially lined by multiple rows of cytologically bland, synovium-like cells
      with positive immunoreactivity to vimentin and CD68 but negative immunoreactivity
      to cytokeratin. The histopathologic findings in this case suggest that it was
      caused by the developmental rests of mucin-secreting mesenchymal cells derived
      from the knee joint.

PMID- 17185246
TI  - Initial 10-year experience of sperm cryopreservation services for cancer
      patients.
AB  - Offering sperm cryopreservation to preserve the fertility of male cancer patients
      is a relatively recent service in Asia. This study analyzed the types of cancer,
      timing of collection, sperm quality, and utilization for reproductive services by
      patients during a 10-year period at a medical center in Taiwan. A total of 75
      oncology patients elected to freeze sperm for fertility preservation at our
      medical center during the initial 10 years of the availability of this service.
      The mean age of the patients was 25.7 years. Storage was discontinued in 13 (17%)
      patients and their survival duration was 13.1 +/- 11.1 months. The utilization
      rate of sperm cryopreservation was 2.8% (75/2642). The types of cancer varied,
      with leukemia (35%), lymphoma (25%), and testicular cancer (13%) comprising the
      largest groups. A significantly lower sperm count was found in patients with
      chronic myelogenous leukemia, suggesting the need for earlier sperm collection
      after initiation of cancer treatment. Only three (4%) patients utilized their
      specimens for reproductive purposes. There was no clinical pregnancy during the
      study period, although one biochemical pregnancy was achieved. The low rates of
      sperm cryostorage for fertility preservation in cancer patients in this study
      suggest that there is a need for greater emphasis of this option for male
      oncology patients whose fertility is likely to be affected by chemotherapeutic
      treatment.

PMID- 17185247
TI  - Spontaneous rupture of a large exogastric hemangioma complicated by
      hemoperitoneum and sepsis.
AB  - Hemangiomas are benign congenital tumors of mature blood vessels and usually
      consist of dense masses of capillaries or larger blood vessels. Hemangioma of the
      stomach presenting with spontaneous rupture and sepsis is rare. We report a 22
      year-old male who presented at the emergency room with sudden-onset epigastric
      pain, intractable nausea, and vomiting. Fever, tachycardia, leukocytosis and
      peritonitis were found on examination after admission. Computed tomography
      revealed a single, well-defined homogeneous lesion measuring approximately 6 x 8
      x 9 cm in size over the left upper abdomen and hemoperitoneum. Laparotomy was
      performed because of intra-abdominal hemorrhage, peritonitis, and fever. During
      the operation, a dark red tumor was found on the greater curvature side of the
      stomach, accompanied by bleeding and hemoperitoneum. The tumor was removed and a
      wedge resection of the stomach and partial omentectomy were performed.
      Histopathologic examination of the excised tumor revealed mixed cavernous
      capillary hemangioma with central necrosis. The postoperative course was
      uncomplicated. The pathogenesis of spontaneous rupture and sepsis in this case
      may have resulted from pedicle torsion accompanied by ischemia, central necrosis,
      rupture of hemangioma and subsequent peritonitis and sepsis.

PMID- 17185248
TI  - Is cost-effectiveness analysis necessary for national health insurance?

PMID- 17185249
TI  - Environmental Justice and the NIEHS.

PMID- 17185250
TI  - Statistical issues in farmworker studies.

PMID- 17185251
TI  - Hormesis is biology, not religion.

PMID- 17185253
TI  - Cox models for ecologic time-series data?

PMID- 17185261
TI  - Change of venue: taking environmental mutagen research to the developing world.

PMID- 17185263
TI  - Signs of the times: biomarkers in perspective.

PMID- 17185264
TI  - Obstructing authority: does the EPA have the power to ensure commercial chemicals
      are safe?

PMID- 17185265
TI  - Fluid movement.

PMID- 17185266
TI  - Unidentified inert ingredients in pesticides: implications for human and
      environmental health.
AB  - BACKGROUND: By statute or regulation in the United States and elsewhere,
      pesticide ingredients are divided into two categories: active and inert
      (sometimes referred to as other ingredients, adjuvants, or coformulants). Despite
      their name, inert ingredients may be biologically or chemically active and are
      labeled inert only because of their function in the formulated product. Most of
      the tests required to register a pesticide are performed with the active
      ingredient alone, not the full pesticide formulation. Inert ingredients are
      generally not identified on product labels and are often claimed to be
      confidential business information. OBJECTIVES: In this commentary, we describe
      the shortcomings of the current procedures for assessing the hazards of pesticide
      formulations and demonstrate that inert ingredients can increase the toxicity of
      and potential exposure to pesticide formulations. DISCUSSION: Inert ingredients
      can increase the ability of pesticide formulations to affect significant
      toxicologic end points, including developmental neurotoxicity, genotoxicity, and
      disruption of hormone function. They can also increase exposure by increasing
      dermal absorption, decreasing the efficacy of protective clothing, and increasing
      environmental mobility and persistence. Inert ingredients can increase the
      phytotoxicity of pesticide formulations as well as the toxicity to fish,
      amphibians, and microorganisms. CONCLUSIONS: Pesticide registration should
      require full assessment of formulations. Evaluations of pesticides under the
      National Environmental Policy Act, the Endangered Species Act, and similar
      statutes should include impact assessment of formulations. Environmental
      monitoring for pesticides should include inert ingredients. To enable independent
      research and risk assessment, inert ingredients should be identified on product
      labels.

PMID- 17185267
TI  - Global environmental change: what can health care providers and the environmental
      health community do about it now?
AB  - The debate about whether global environmental change is real is now over; in its
      wake is the realization that it is happening more rapidly than predicted. These
      changes constitute a profound challenge to human health, both as a direct threat
      and as a promoter of other risks. We call on health care providers to inform
      themselves about these issues and to become agents of change in their
      communities. It is our responsibility as clinicians to educate patients and their
      communities on the connections between regressive policies, unsustainable
      behaviors, global environmental changes, and threats to health and security. We
      call on professional organizations to assist in educating their members about
      these issues, in helping clinicians practice behavior change with their patients,
      and in adding their voices to this issue in our statehouses and Congress. We call
      for the development of carbon and other environmental-labeling of consumer
      products so individuals can make informed choices; we also call for the rapid
      implementation of policies that provide tangible economic incentives for choosing
      environmentally sustainable products and services. We urge the environmental
      health community to take up the challenge of developing a global environmental
      health index that will incorporate human health into available "planetary health"
      metrics and that can be used as a policy tool to evaluate the impact of
      interventions and document spatial and temporal shifts in the healthfulness of
      local areas. Finally, we urge our political, business, public health, and
      academic leaders to heed these environmental warnings and quickly develop
      regulatory and policy solutions so that the health of populations and the
      integrity of their environments will be ensured for future generations.

PMID- 17185268
TI  - Prioritizing environmental issues around the world: opinions from an
      international Central and Eastern European environmental health conference.
AB  - BACKGROUND: As the next generation of scientists enters the field of
      environmental health, it is imperative that they view their contributions in the
      context of global environmental stewardship. In this commentary, a group of
      international graduate students facilitated by three experienced environmental
      health scientists present their views on what they consider to be the global
      environmental health concerns of today. This group convened initially in October
      2004 at an international health conference in Prague, Czech Republic. OBJECTIVES:
      In this report we identify perceived environmental health concerns that exist
      around the world, with a focus on Central and Eastern Europe. Additionally, we
      address these perceived problems and offers some potential solutions. DISCUSSION:
      At the meeting, students were invited to participate in two panel discussions.
      One group of young international scientists identified several significant global
      environmental health concerns, including air pollution, occupational hazards, and
      risk factors that may exacerbate current environmental health issues. The second
      panel determined that communication, education, and regulation were the
      mechanisms for addressing current environmental challenges. CONCLUSIONS: In this
      commentary we expand on the views presented at the meeting and represent the
      concerns of young investigators from nine different countries. We provide ideas
      about and support the exchange of information between developed and developing
      countries on how to handle the environmental health challenges that face the
      world today.

PMID- 17185269
TI  - Nanoparticles: health effects--pros and cons.
AB  - With the advent of nanotechnology, the prospects for using engineered
      nanomaterials with diameters of < 100 nm in industrial applications, medical
      imaging, disease diagnoses, drug delivery, cancer treatment, gene therapy, and
      other areas have progressed rapidly. The potential for nanoparticles (NPs) in
      these areas is infinite, with novel new applications constantly being explored.
      The possible toxic health effects of these NPs associated with human exposure are
      unknown. Many fine particles generally considered "nuisance dusts" are likely to
      acquire unique surface properties when engineered to nanosize and may exhibit
      toxic biological effects. Consequently, the nuisance dust may be transported to
      distant sites and could induce adverse health effects. In addition the beneficial
      uses of NPs in drug delivery, cancer treatment, and gene therapy may cause
      unintentional human exposure. Because of our lack of knowledge about the health
      effects associated with NP exposure, we have an ethical duty to take
      precautionary measures regarding their use. In this review we highlight the
      possible toxic human health effects that can result from exposure to ultrafine
      particles (UFPs) generated by anthropogenic activities and their cardiopulmonary
      outcomes. The comparability of engineered NPs to UFPs suggests that the human
      health effects are likely to be similar. Therefore, it is prudent to elucidate
      their toxicologic effect to minimize occupational and environmental exposure.
      Highlighting the human health outcomes caused by UFPs is not intended to give a
      lesser importance to either the unprecedented technologic and industrial rewards
      of the nanotechnology or their beneficial human uses.

PMID- 17185270
TI  - In vivo assessment of arsenic bioavailability in rice and its significance for
      human health risk assessment.
AB  - BACKGROUND: Millions of people worldwide consume arsenic-contaminated rice;
      however, little is known about the uptake and bioavailability of arsenic species
      after arsenic-contaminated rice ingestion. OBJECTIVES: In this study, we assessed
      arsenic speciation in greenhouse-grown and supermarket-bought rice, and
      determined arsenic bioavailability in cooked rice using an in vivo swine model.
      RESULTS: In supermarket-bought rice, arsenic was present entirely in the
      inorganic form compared to greenhouse-grown rice (using irrigation water
      contaminated with sodium arsenate), where most (approximately 86%) arsenic was
      present as dimethylarsinic acid (organic arsenic). Because of the low absolute
      bioavailability of dimethylarsinic acid and the high proportion of
      dimethylarsinic acid in greenhouse-grown rice, only 33 +/- 3% (mean +/- SD) of
      the total rice-bound arsenic was bioavailable. Conversely, in supermarket-bought
      rice cooked in water contaminated with sodium arsenate, arsenic was present
      entirely in the inorganic form, and bioavailability was high (89 +/- 9%).
      CONCLUSIONS: These results indicate that arsenic bioavailability in rice is
      highly dependent on arsenic speciation, which in turn can vary depending on rice
      cultivar, arsenic in irrigation water, and the presence and nature of arsenic
      speciation in cooking water. Arsenic speciation and bioavailability are therefore
      critical parameters for reducing uncertainties when estimating exposure from the
      consumption of rice grown and cooked using arsenic-contaminated water.

PMID- 17185271
TI  - Elevation of cellular BPDE uptake by human cells: a possible factor contributing
      to co-carcinogenicity by arsenite.
AB  - BACKGROUND: Arsenite (iAsIII) can promote mutagenicity and carcinogenicity of
      other carcinogens. Considerable attention has focused on interference with DNA
      repair by inorganic arsenic, especially the nucleotide excision repair (NER)
      pathway, whereas less is known about the effect of arsenic on the induction of
      DNA damage by other agents. OBJECTIVES: We examined how arsenic modulates DNA
      damage by other chemicals. METHODS: We used an NER-deficient cell line to dissect
      DNA damage induction from DNA repair and to examine the effects of iAsIII on the
      formation of benzo[a]pyrene diol epoxide (BPDE)-DNA adducts. RESULTS: We found
      that pretreatment with iAsIII at subtoxic concentrations (10 microM) led to
      enhanced formation of BPDE-DNA adducts. Reduced glutathione levels, glutathione S
      transferase activity and chromatin accessibility were also measured after iAsIII
      treatment, but none of these factors appeared to account for the enhanced
      formation of DNA adducts. However, we found that pretreatment with iAsIII
      increased the cellular uptake of BPDE in a dose-dependent manner. CONCLUSIONS:
      Our results suggest that iAsIII enhanced the formation of BPDE-DNA adducts by
      increasing the cellular uptake of BPDE. Therefore, the ability of arsenic to
      increase the bioavailability of other carcinogens may contribute to arsenic co
      carcinogenicity.

PMID- 17185272
TI  - Fonofos exposure and cancer incidence in the agricultural health study.
AB  - BACKGROUND: The Agricultural Health Study (AHS) is a prospective cohort study of
      licensed pesticide applicators from Iowa and North Carolina enrolled 1993-1997
      and followed for incident cancer through 2002. A previous investigation in this
      cohort linked exposure to the organophosphate fonofos with incident prostate
      cancer in subjects with family history of prostate cancer. OBJECTIVES: This
      finding along with findings of associations between organophosphate pesticides
      and cancer more broadly led to this study of fonofos and risk of any cancers
      among 45,372 pesticide applicators enrolled in the AHS. METHODS: Pesticide
      exposure and other data were collected using self-administered questionnaires.
      Poisson regression was used to calculate rate ratios (RRs) and 95% confidence
      intervals (CIs) while controlling for potential confounders. RESULTS: Relative to
      the unexposed, leukemia risk was elevated in the highest category of lifetime (RR
      = 2.24; 95% CI, 0.94-5.34, Ptrend = 0.07) and intensity-weighted exposure-days
      (RR = 2.67; 95% CI, 1.06-6.70, Ptrend = 0.04), a measure that takes into account
      factors that modify pesticide exposure. Although prostate cancer risk was
      unrelated to fonofos use overall, among applicators with a family history of
      prostate cancer, we observed a significant dose-response trend for lifetime
      exposure-days (Ptrend = 0.02, RR highest tertile vs. unexposed = 1.77, 95% CI,
      1.03-3.05; RRinteraction = 1.28, 95% CI, 1.07-1.54). Intensity-weighted results
      were similar. No associations were observed with other examined cancer sites.
      CONCLUSIONS: Further study is warranted to confirm findings with respect to
      leukemia and determine whether genetic susceptibility modifies prostate cancer
      risk from pesticide exposure.

PMID- 17185273
TI  - Parabens as urinary biomarkers of exposure in humans.
AB  - BACKGROUND: Parabens appear frequently as antimicrobial preservatives in cosmetic
      products, in pharmaceuticals, and in food and beverage processing. In vivo and in
      vitro studies have revealed weak estrogenic activity of some parabens. Widespread
      use has raised concerns about the potential human health risks associated with
      paraben exposure. OBJECTIVES: Assessing human exposure to parabens usually
      involves measuring in urine the conjugated or free species of parabens or their
      metabolites. In animals, parabens are mostly hydrolyzed to p-hydroxybenzoic acid
      and excreted in the urine as conjugates. Still, monitoring urinary concentrations
      of p-hydroxybenzoic acid is not necessarily the best way to assess exposure to
      parabens. p-hydroxybenzoic acid is a nonspecific biomarker, and the varying
      estrogenic bioactivities of parabens require specific biomarkers. Therefore, we
      evaluated the use of free and conjugated parent parabens as new biomarkers for
      human exposure to these compounds. RESULTS: We measured the urinary
      concentrations of methyl, ethyl, n-propyl, butyl (n- and iso-), and benzyl
      parabens in a demographically diverse group of 100 anonymous adults. We detected
      methyl and n-propyl parabens at the highest median concentrations (43.9 ng/mL and
      9.05 ng/mL, respectively) in nearly all (> 96%) of the samples. We also detected
      other parabens in more than half of the samples (ethyl, 58%; butyl, 69%). Most
      important, however, we found that parabens in urine appear predominantly in their
      conjugated forms. CONCLUSIONS: The results, demonstrating the presence of urinary
      conjugates of parabens in humans, suggest that such conjugated parabens could be
      used as exposure biomarkers. Additionally, the fact that conjugates appear to be
      the main urinary products of parabens may be important for risk assessment.

PMID- 17185274
TI  - Arsenic exposure and age and sex-specific risk for skin lesions: a population
      based case-referent study in Bangladesh.
AB  - BACKGROUND: The objective of this population-based case-referent study in Matlab,
      Bangladesh, was to assess the susceptibility to arsenic-induced skin lesions by
      age and sex, in a population drinking water from As-contaminated tube wells.
      METHODS: Identification of As-related skin lesions was carried out in three
      steps: a) screening of the entire population > 4 years of age (n = 166,934) by
      trained field teams; b) diagnosis of suspected As-related cases by physicians;
      and c) confirmation by experts based on physicians' records and photographs. A
      total of 504 cases with skin lesions were confirmed. We randomly selected 2,201
      referents from the Matlab health and demographic surveillance system; 1,955 were
      eligible, and 1,830 (94%) were available for participation in the study.
      Individual history of As exposure was based on information obtained during
      interviews and included all drinking-water sources used since 1970 and
      concentrations of As (assessed by atomic absorption spectrophotometry) in all the
      tube wells used. RESULTS: Cases had been exposed to As more than referents
      (average exposure since 1970: male cases, 200 microg/L; female cases, 211
      microg/L; male referents, 143 microg/L; female referents, 155 microg/L). We found
      a dose-response relationship for both sexes (p < 0.001) and increased risk with
      increasing socioeconomic status. Males had a higher risk of obtaining skin
      lesions than females (odds ratio 10.9 vs. 5.78) in the highest average exposure
      quintile (p = 0.005). Start of As exposure (cumulative exposure) before 1 year of
      age was not associated with higher risk of obtaining skin lesions compared to
      start of As exposure later in life. CONCLUSIONS: The results demonstrate that
      males are more susceptible than females to develop skin lesions when exposed to
      As in water from tube wells.

PMID- 17185275
TI  - The World Trade Center disaster and the health of workers: five-year assessment
      of a unique medical screening program.
AB  - BACKGROUND: Approximately 40,000 rescue and recovery workers were exposed to
      caustic dust and toxic pollutants following the 11 September 2001 attacks on the
      World Trade Center (WTC). These workers included traditional first responders,
      such as firefighters and police, and a diverse population of construction,
      utility, and public sector workers. METHODS: To characterize WTCrelated health
      effects, the WTC Worker and Volunteer Medical Screening Program was established.
      This multicenter clinical program provides free standardized examinations to
      responders. Examinations include medical, mental health, and exposure assessment
      questionnaires; physical examinations; spirometry; and chest X rays. RESULTS: Of
      9,442 responders examined between July 2002 and April 2004, 69% reported new or
      worsened respiratory symptoms while performing WTC work. Symptoms persisted to
      the time of examination in 59% of these workers. Among those who had been
      asymptomatic before September 11, 61% developed respiratory symptoms while
      performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital
      capacity (FVC) was low in 21%; and obstruction was present in 5%. Among
      nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S.
      population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the
      U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities
      were significantly associated with early arrival at the site. CONCLUSION: WTC
      responders had exposure-related increases in respiratory symptoms and pulmonary
      function test abnormalities that persisted up to 2.5 years after the attacks.
      Longterm medical monitoring is required to track persistence of these
      abnormalities and identify late effects, including possible malignancies. Lessons
      learned should guide future responses to civil disasters.

PMID- 17185276
TI  - Isolation of Staphylococcus aureus and antibiotic-resistant Staphylococcus aureus
      from residential indoor bioaerosols.
AB  - OBJECTIVE: In this study we evaluated the levels of Staphylococcus aureus and
      antibiotic-resistant S. aureus in colony-forming units (CFU) per cubic meter of
      air. DESIGN: We used Andersen two-stage samplers to collect bioaerosol samples
      from 24 houses in El Paso, Texas, using tryptic soy agar as the collection media,
      followed by the replicate plate method on Chapman Stone selective medium to
      isolate S. aureus. The Kirby-Bauer disk diffusion method was used to determine
      antibiotic resistance to ampicillin, penicillin, and cefaclor, which represent
      two distinct classes of antibiotics. RESULTS: The average recovered concentration
      of respirable heterotrophic organisms found outside each home was 345.38 CFU/m3,
      with an average of 12.63 CFU/m3 for S. aureus. The average recovered
      concentration of respirable heterotrophic organisms found inside each home was
      460.23 CFU/m3, with an average of 15.39 CFU/m3 for S. aureus. The respirable S.
      aureus recovered from inside each home had an average resistance of 54.59% to
      ampicillin and 60.46% to penicillin. Presence of cefaclor-resistant and of
      multidrug-resistant S. aureus was the same, averaging 13.20% per house. The
      respirable S. aureus recovered from outside each home had an average resistance
      of 34.42% to ampicillin and 41.81% to penicillin. Presence of cefaclor-resistant
      and of multidrug-resistant S. aureus was the same, averaging 13.96% per house.
      CONCLUSIONS: This study indicates that antibiotic-resistant bioaerosols are
      commonly found within residential homes. Our results also suggest that resistant
      strains of airborne culturable S. aureus are present in higher concentrations
      inside the study homes than outside the homes.

PMID- 17185277
TI  - Urinary perchlorate and thyroid hormone levels in adolescent and adult men and
      women living in the United States.
AB  - BACKGROUND: Perchlorate is commonly found in the environment and known to inhibit
      thyroid function at high doses. Assessing the potential effect of low-level
      exposure to perchlorate on thyroid function is an area of ongoing research.
      OBJECTIVES: We evaluated the potential relationship between urinary levels of
      perchlorate and serum levels of thyroid stimulating hormone (TSH) and total
      thyroxine (T4) in 2,299 men and women, > or = 12 years of age, participating in
      the National Health and Nutrition Examination Survey (NHANES) during 2001-2002.
      METHODS: We used multiple regression models of T4 and TSH that included
      perchlorate and covariates known to be or likely to be associated with T4 or TSH
      levels: age, race/ethnicity, body mass index, estrogen use, menopausal status,
      pregnancy status, premenarche status, serum C-reactive protein, serum albumin,
      serum cotinine, hours of fasting, urinary thiocyanate, urinary nitrate, and
      selected medication groups. RESULTS: Perchlorate was not a significant predictor
      of T4 or TSH levels in men. For women overall, perchlorate was a significant
      predictor of both T4 and TSH. For women with urinary iodine < 100 microg/L,
      perchlorate was a significant negative predictor of T4 (p < 0.0001) and a
      positive predictor of TSH (p = 0.001). For women with urinary iodine > or = 100
      microg/L, perchlorate was a significant positive predictor of TSH (p = 0.025) but
      not T4 (p = 0.550). CONCLUSIONS: These associations of perchlorate with T4 and
      TSH are coherent in direction and independent of other variables known to affect
      thyroid function, but are present at perchlorate exposure levels that were
      unanticipated based on previous studies.

PMID- 17185278
TI  - Whole-body lifetime occupational lead exposure and risk of Parkinson's disease.
AB  - BACKGROUND: Several epidemiologic studies have suggested an association between
      Parkinson's disease (PD) and exposure to heavy metals using subjective exposure
      measurements. OBJECTIVES: We investigated the association between objective
      chronic occupational lead exposure and the risk of PD. METHODS: We enrolled 121
      PD patients and 414 age, sex, and race, frequency-matched controls in a case
      control study. As an indicator of chronic Pb exposure, we measured concentrations
      of tibial and calcaneal bone Pb stores using 109Cadmium excited K-series X-ray
      fluorescence. As an indicator of recent exposure, we measured blood Pb
      concentration. We collected occupational data on participants from 18 years of
      age until the age at enrollment, and an industrial hygienist determined the
      duration and intensity of environmental Pb exposure. We employed physiologically
      based pharmacokinetic modeling to combine these data, and we estimated wholebody
      lifetime Pb exposures for each individual. Logistic regression analysis produced
      estimates of PD risk by quartile of lifetime Pb exposure. RESULTS: Risk of PD was
      elevated by > 2-fold [odds ratio = 2.27 (95% confidence interval, 1.13-4.55); p =
      0.021] for individuals in the highest quartile for lifetime lead exposure
      relative to the lowest quartile, adjusting for age, sex, race, smoking history,
      and coffee and alcohol consumption. The associated risk of PD for the second and
      third quartiles were elevated but not statistically significant at the alpha =
      0.05 level. CONCLUSIONS: These results provide an objective measure of chronic Pb
      exposure and confirm our earlier findings that occupational exposure to Pb is a
      risk factor for PD.

PMID- 17185279
TI  - Using supervised principal components analysis to assess multiple pollutant
      effects.
AB  - BACKGROUND: Many investigations of the adverse health effects of multiple air
      pollutants analyze the time series involved by simultaneously entering the
      multiple pollutants into a Poisson log-linear model. This method can yield
      unstable parameter estimates when the pollutants involved suffer high
      intercorrelation; therefore, traditional approaches to dealing with
      multicollinearity, such as principal component analysis (PCA), have been promoted
      in this context. OBJECTIVES: A characteristic of PCA is that its construction
      does not consider the relationship between the covariates and the adverse health
      outcomes. A refined version of PCA, supervised principal components analysis
      (SPCA), is proposed that specifically addresses this issue. METHODS: Models
      controlling for longterm trends and weather effects were used in conjunction with
      each SPCA and PCA to estimate the association between multiple air pollutants and
      mortality for U.S. cities. The methods were compared further via a simulation
      study. RESULTS: Simulation studies demonstrated that SPCA, unlike PCA, was
      successful in identifying the correct subset of multiple pollutants associated
      with mortality. Because of this property, SPCA and PCA returned different
      estimates for the relationship between air pollution and mortality. CONCLUSIONS:
      Although a number of methods for assessing the effects of multiple pollutants
      have been proposed, such methods can falter in the presence of high correlation
      among pollutants. Both PCA and SPCA address this issue. By allowing the exclusion
      of pollutants that are not associated with the adverse health outcomes from the
      mixture of pollutants selected, SPCA offers a critical improvement over PCA.

PMID- 17185280
TI  - Mold and endotoxin levels in the aftermath of Hurricane Katrina: a pilot project
      of homes in New Orleans undergoing renovation.
AB  - BACKGROUND: After Hurricane Katrina, many New Orleans homes remained flooded for
      weeks, promoting heavy microbial growth. OBJECTIVES: A small demonstration
      project was conducted November 2005-January 2006 aiming to recommend safe
      remediation techniques and safe levels of worker protection, and to characterize
      airborne mold and endotoxin throughout cleanup. METHODS: Three houses with
      floodwater lines between 0.3 and 2 m underwent intervention, including disposal
      of damaged furnishings and drywall, cleaning surfaces, drying remaining
      structure, and treatment with a biostatic agent. We measured indoor and outdoor
      bioaerosols before, during, and after intervention. Samples were analyzed for
      fungi [culture, spore analysis, polymerase chain reaction (PCR)] and endotoxin.
      In one house, realtime particle counts were also assessed, and respirator
      efficiency testing was performed to establish workplace protection factors (WPF).
      RESULTS: At baseline, culturable mold ranged from 22,000 to 515,000 colony
      forming units/m3, spore counts ranged from 82,000 to 630,000 spores/m3, and
      endotoxin ranged from 17 to 139 endotoxin units/m3. Culture, spore analysis, and
      PCR indicated that Penicillium, Aspergillus, and Paecilomyces predominated. After
      intervention, levels of mold and endotoxin were generally lower (sometimes,
      orders of magnitude). The average WPF against fungal spores for elastomeric
      respirators was higher than for the N95 respirators. CONCLUSIONS: During baseline
      and intervention, mold and endotoxin levels were similar to those found in
      agricultural environments. We strongly recommend that those entering, cleaning,
      and repairing flood-damaged homes wear respirators at least as protective as
      elastomeric respirators. Recommendations based on this demonstration will benefit
      those involved in the current cleanup activities and will inform efforts to
      respond to future disasters.

PMID- 17185281
TI  - The tobacco industry's role in the 16 Cities Study of secondhand tobacco smoke:
      do the data support the stated conclusions?
AB  - BACKGROUND: Since 1996, the tobacco industry has used the 16 Cities Study
      conclusions that workplace secondhand tobacco smoke (SHS) exposures are lower
      than home exposures to argue that workplace and other smoking restrictions are
      unnecessary. OBJECTIVES: Our goal was to determine the origins and objectives of
      the 16 Cities Study through analysis of internal tobacco industry documents and
      regulatory agency and court records, and to evaluate the validity of the study's
      conclusions. RESULTS: The tobacco industry's purpose in conducting the 16 Cities
      Study was to develop data showing that workplace SHS exposures were negligible,
      using these data to stop smoking restrictions by the U.S. Occupational Safety and
      Health Administration. The extensive involvement of R.J. Reynolds Tobacco Company
      and the tobacco industry's Center for Indoor Air Research in controlling the
      study was not fully disclosed. The study's definition of "smoking workplace"
      included workplaces where smoking was restricted to designated areas or where no
      smoking was observed. This definition substantially reduced the study's reported
      average SHS concentrations in "smoking workplaces" because SHS levels in
      unrestricted smoking workplaces are much greater than in workplaces with
      designated smoking areas or where no smoking occurred. Stratifying the data by
      home smoking status and comparing exposures by workplace smoking status, however,
      indicates that smoke-free workplaces would halve the total SHS exposure of those
      living with smokers and virtually eliminate SHS exposure for most others.
      CONCLUSIONS: Data in the 16 Cities Study reveal that smoke-free workplaces would
      dramatically reduce total SHS exposure, providing significant worker and public
      health benefits.

PMID- 17185283
TI  - Exposures to environmental toxicants and attention deficit hyperactivity disorder
      in U.S. children.
AB  - OBJECTIVE: The purpose of this study was to examine the association of exposures
      to tobacco smoke and environmental lead with attention deficit hyperactivity
      disorder (ADHD). METHODS: Data were obtained from the National Health and
      Nutrition Examination Survey 1999-2002. Prenatal and postnatal tobacco exposure
      was based on parent report; lead exposure was measured using blood lead
      concentration. ADHD was defined as having current stimulant medication use and
      parent report of ADHD diagnosed by a doctor or health professional. RESULTS: Of
      4,704 children 4-15 years of age, 4.2% were reported to have ADHD and stimulant
      medication use, equivalent to 1.8 million children in the United States. In
      multivariable analysis, prenatal tobacco exposure [odds ratio (OR) = 2.5; 95%
      confidence interval (CI), 1.2-5.2] and higher blood lead concentration (first vs.
      fifth quintile, OR = 4.1; 95% CI, 1.2-14.0) were significantly associated with
      ADHD. Postnatal tobacco smoke exposure was not associated with ADHD (OR = 0.6;
      95% CI, 0.3-1.3; p = 0.22). If causally linked, these data suggest that prenatal
      tobacco exposure accounts for 270,000 excess cases of ADHD, and lead exposure
      accounts for 290,000 excess cases of ADHD in U.S. children. CONCLUSIONS: We
      conclude that exposure to prenatal tobacco and environmental lead are risk
      factors for ADHD in U.S. children.

PMID- 17185282
TI  - Workgroup report: public health strategies for reducing aflatoxin exposure in
      developing countries.
AB  - Consecutive outbreaks of acute aflatoxicosis in Kenya in 2004 and 2005 caused >
      150 deaths. In response, the Centers for Disease Control and Prevention and the
      World Health Organization convened a workgroup of international experts and
      health officials in Geneva, Switzerland, in July 2005. After discussions
      concerning what is known about aflatoxins, the workgroup identified gaps in
      current knowledge about acute and chronic human health effects of aflatoxins,
      surveillance and food monitoring, analytic methods, and the efficacy of
      intervention strategies. The workgroup also identified public health strategies
      that could be integrated with current agricultural approaches to resolve gaps in
      current knowledge and ultimately reduce morbidity and mortality associated with
      the consumption of aflatoxin-contaminated food in the developing world. Four
      issues that warrant immediate attention were identified: a) quantify the human
      health impacts and the burden of disease due to aflatoxin exposure; b) compile an
      inventory, evaluate the efficacy, and disseminate results of ongoing intervention
      strategies; c) develop and augment the disease surveillance, food monitoring,
      laboratory, and public health response capacity of affected regions; and d)
      develop a response protocol that can be used in the event of an outbreak of acute
      aflatoxicosis. This report expands on the workgroup's discussions concerning
      aflatoxin in developing countries and summarizes the findings.

PMID- 17185284
TI  - Dog ownership enhances symptomatic responses to air pollution in children with
      asthma.
AB  - BACKGROUND: Experimental data suggest that asthma exacerbation by ambient air
      pollutants is enhanced by exposure to endotoxin and allergens; however, there is
      little supporting epidemiologic evidence. METHODS: We evaluated whether the
      association of exposure to air pollution with annual prevalence of chronic cough,
      phlegm production, or bronchitis was modified by dog and cat ownership
      (indicators of allergen and endotoxin exposure). The study population consisted
      of 475 Southern California children with asthma from a longitudinal cohort of
      participants in the Children's Health Study. We estimated average annual ambient
      exposure to nitrogen dioxide, ozone, particulate matter < 10, 2.5, and 10-2.5
      microm in aerodynamic diameter (PM10, PM2.5, and PM10-2.5, respectively),
      elemental and organic carbon, and acid vapor from monitoring stations in each of
      the 12 study communities. Multivariate models were used to examine the effect of
      yearly variation of each pollutant. Effects were scaled to the variability that
      is common for each pollutant in representative communities in Southern
      California. RESULTS: Among children owning a dog, there were strong associations
      between bronchitic symptoms and all pollutants examined. Odds ratios ranged from
      1.30 per 4.2 microg/m3 for PM10-2.5 [95% confidence interval (CI), 0.91-1.87) to
      1.91 per 1.2 microg/m3 for organic carbon (95% CI, 1.34-2.71). Effects were
      somewhat larger among children who owned both a cat and dog. There were no
      effects or small effects with wide CIs among children without a dog and among
      children who owned only a cat. CONCLUSION: Our results suggest that dog
      ownership, a source of residential exposure to endotoxin, may worsen the
      relationship between air pollution and respiratory symptoms in asthmatic
      children.

PMID- 17185285
TI  - Early environmental exposures and intracellular Th1/Th2 cytokine profiles in 24
      month-old children living in an agricultural area.
AB  - BACKGROUND: Children who reside in agricultural settings are potentially exposed
      to higher levels of organophosphate (OP) pesticides, endotoxin, and allergens
      than their urban counterparts. Endotoxin and allergens stimulate maturation of
      the immune response in early childhood, but little is known about the effect of
      exposures to OPs or to the three combined. OBJECTIVES: In this study, we
      investigated the relationships between these exposures and T-helper 1 (Th1) and T
      helper 2 (Th2) cytokines, biomarkers of allergic asthma, in the subjects of
      CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a
      longitudinal birth cohort in Salinas Valley, California. Exposures were
      ascertained by interviewer-administered questionnaires and by home visits, and
      clinical diagnoses were abstracted from medical records. Blood samples were
      collected at 12 and 24 months of age and analyzed for Th1/Th2 status by flow
      cytometric detection of intracellular interferon-gamma/interleukin-4 cytokine
      expression. FINDINGS: Mean Th2 levels were significantly higher in children with
      doctor-diagnosed asthma and children with wheezing at 2 years of age. In a
      multiple linear regression model, exclusive breast-feeding at 1 month and pet
      ownership were associated with 35.3% (p < 0.01) and 34.5% (p = 0.01) increases in
      Th1, respectively. Maternal agricultural work and presence of gas stove in the
      home were associated with a 25.9% increase (p = 0.04) and 46.5% increase (p <
      0.01) in Th2, respectively. CONCLUSIONS: Asthma and wheeze outcomes in children
      at 24 months of age are associated with elevated Th2 status in children at an
      early age. Our data further suggest that early exposures to an agricultural
      environment, breast-feeding, pets, and gas stoves affect the development of
      children's Th1/Th2 immune response.

PMID- 17185287
TI  - An approach for assessing human health vulnerability and public health
      interventions to adapt to climate change.
AB  - Assessments of the potential human health impacts of climate change are needed to
      inform the development of adaptation strategies, policies, and measures to lessen
      projected adverse impacts. We developed methods for country-level assessments to
      help policy makers make evidence-based decisions to increase resilience to
      current and future climates, and to provide information for national
      communications to the United Nations Framework Convention on Climate Change. The
      steps in an assessment should include the following: a) determine the scope of
      the assessment; b) describe the current distribution and burden of climate
      sensitive health determinants and outcomes; c) identify and describe current
      strategies, policies, and measures designed to reduce the burden of climate
      sensitive health determinants and outcomes; d) review the health implications of
      the potential impacts of climate variability and change in other sectors; e)
      estimate the future potential health impacts using scenarios of future changes in
      climate, socioeconomic, and other factors; f) synthesize the results; and g)
      identify additional adaptation policies and measures to reduce potential negative
      health impacts. Key issues for ensuring that an assessment is informative,
      timely, and useful include stakeholder involvement, an adequate management
      structure, and a communication strategy.

PMID- 17185286
TI  - Response inhibition during Differential Reinforcement of Low Rates (DRL)
      schedules may be sensitive to low-level polychlorinated biphenyl, methylmercury,
      and lead exposure in children.
AB  - BACKGROUND: Animal studies have shown that exposure to common, low-level
      environmental contaminants [e.g., polychlorinated biphenyls (PCBs), lead] causes
      excessive and inappropriate responding on intermittent reinforcement schedules.
      The Differential Reinforcement of Low Rates task (DRL) has been shown to be
      especially sensitive to low-level PCB exposure in monkeys. OBJECTIVES: We
      investigated the relationships between prenatal PCB and postnatal Pb exposure
      performance on a DRL schedule in children. We predicted that a) prenatal PCB
      exposure would reduce interresponse times (IRTs) and reinforcements earned, and
      b) postnatal Pb exposure would reduce IRTs and reinforcements earned. METHODS: We
      tested 167 children on a DRL20 (20 sec) reinforcement schedule, and recorded IRTs
      and the number of reinforced responses across the session. We measured prenatal
      PCB exposure (cord blood), methylmercury (MeHg) (maternal hair), and postnatal Pb
      exposure (venous blood), and > 50 potentially confounding variables. RESULTS:
      Results indicated impaired performance in children exposed to PCBs, MeHg, and Pb.
      Children prenatally exposed to PCBs responded excessively, with significantly
      lower IRTs and fewer reinforcers earned across the session. In addition, exposure
      to either MeHg or Pb predicted statistically significant impairments of a similar
      magnitude to those for PCBs, and the associated impairments of all three
      contaminants (PCB, MeHg, and Pb) were statistically independent of one another.
      CONCLUSIONS: These results, taken with animal literature, argue the high
      sensitivity of DRL performance to low-level PCB, MeHg, and Pb exposure. Future
      research should employ behavioral tasks in children, such as DRL, that have been
      demonstrably sensitive to low-level PCB, MeHg, and Pb exposure in animals.

PMID- 17185289
TI  - Assessment of human health vulnerability to climate variability and change in
      Cuba.
AB  - In this study we assessed the potential effects of climate variability and change
      on population health in Cuba. We describe the climate of Cuba as well as the
      patterns of climate-sensitive diseases of primary concern, particularly dengue
      fever. Analyses of the associations between climatic anomalies and disease
      patterns highlight current vulnerability to climate variability. We describe
      current adaptations, including the application of climate predictions to prevent
      disease outbreaks. Finally, we present the potential economic costs associated
      with future impacts due to climate change. The tools used in this study can be
      useful in the development of appropriate and effective adaptation options to
      address the increased climate variability associated with climate change.

PMID- 17185288
TI  - Comparative risk assessment of the burden of disease from climate change.
AB  - The World Health Organization has developed standardized comparative risk
      assessment methods for estimating aggregate disease burdens attributable to
      different risk factors. These have been applied to existing and new models for a
      range of climate-sensitive diseases in order to estimate the effect of global
      climate change on current disease burdens and likely proportional changes in the
      future. The comparative risk assessment approach has been used to assess the
      health consequences of climate change worldwide, to inform decisions on
      mitigating greenhouse gas emissions, and in a regional assessment of the Oceania
      region in the Pacific Ocean to provide more location-specific information
      relevant to local mitigation and adaptation decisions. The approach places
      climate change within the same criteria for epidemiologic assessment as other
      health risks and accounts for the size of the burden of climate-sensitive
      diseases rather than just proportional change, which highlights the importance of
      small proportional changes in diseases such as diarrhea and malnutrition that
      cause a large burden. These exercises help clarify important knowledge gaps such
      as a relatively poor understanding of the role of nonclimatic factors
      (socioeconomic and other) that may modify future climatic influences and a lack
      of empiric evidence and methods for quantifying more complex climate-health
      relationships, which consequently are often excluded from consideration. These
      exercises highlight the need for risk assessment frameworks that make the best
      use of traditional epidemiologic methods and that also fully consider the
      specific characteristics of climate change. These include the longterm and
      uncertain nature of the exposure and the effects on multiple physical and biotic
      systems that have the potential for diverse and widespread effects, including
      high-impact events.

PMID- 17185290
TI  - National assessment of human health effects of climate change in Portugal:
      approach and key findings.
AB  - In this study we investigated the potential impact of climate change in Portugal
      on heat-related mortality, air pollution-related health effects, and selected
      vectorborne diseases. The assessment used climate scenarios from two regional
      climate models for a range of future time periods. The annual heat-related death
      rates in Lisbon may increase from between 5.4 and 6 per 100,000 in 1980-1998 to
      between 8.5 and 12.1 by the 2020s and to a maximum of 29.5 by the 2050s, if no
      adaptations occur. The projected warmer and more variable weather may result in
      better dispersion of nitrogen dioxide levels in winter, whereas the higher
      temperatures may reduce air quality during the warmer months by increasing
      tropospheric ozone levels. We estimated the future risk of zoonoses using
      ecologic scenarios to describe future changes in vectors and parasites. Malaria
      and schistosomiasis, which are currently not endemic in Portugal, are more
      sensitive to the introduction of infected vectors than to temperature changes.
      Higher temperatures may increase the transmission risk of zoonoses that are
      currently endemic to Portugal, such as leishmaniasis, Lyme disease, and
      Mediterranean spotted fever.

PMID- 17185291
TI  - Climate variability and change and their potential health effects in small island
      states: information for adaptation planning in the health sector.
AB  - Small island states are likely the countries most vulnerable to climate
      variability and longterm climate change. Climate models suggest that small island
      states will experience warmer temperatures and changes in rainfall, soil moisture
      budgets, prevailing winds (speed and direction), and patterns of wave action. El
      Nino events likely will strengthen shortterm and interannual climate variations.
      In addition, global mean sea level is projected to increase by 0.09-0.88 m by
      2100, with variable effects on regional and local sea level. To better understand
      the potential human health consequences of these projected changes, a series of
      workshops and a conference organized by the World Health Organization, in
      partnership with the World Meteorological Organization and the United Nations
      Environment Programme, addressed the following issues: the current distribution
      and burden of climate-sensitive diseases in small island states, the potential
      future health impacts of climate variability and change, the interventions
      currently used to reduce the burden of climate-sensitive diseases, additional
      interventions that are needed to adapt to current and future health impacts, and
      the health implications of climate variability and change in other sectors.
      Information on these issues is synthesized and key recommendations are identified
      for improving the capacity of the health sector to anticipate and prepare for
      climate variability and change in small island states.

PMID- 17185292
TI  - Climate change, health, and vulnerability in Canadian northern Aboriginal
      communities.
AB  - BACKGROUND: Canada has recognized that Aboriginal and northern communities in the
      country face unique challenges and that there is a need to expand the assessment
      of vulnerabilities to climate change to include these communities. Evidence
      suggests that Canada's North is already experiencing significant changes in its
      climate--changes that are having negative impacts on the lives of Aboriginal
      people living in these regions. Research on climate change and health impacts in
      northern Canada thus far has brought together Aboriginal community members,
      government representatives, and researchers and is charting new territory.
      METHODS AND RESULTS: In this article we review experiences from two projects that
      have taken a community-based dialogue approach to identifying and assessing the
      effects of and vulnerability to climate change and the impact on the health in
      two Inuit regions of the Canadian Arctic. CONCLUSIONS: The results of the two
      case projects that we present argue for a multi-stakeholder, participatory
      framework for assessment that supports the necessary analysis, understanding, and
      enhancement of capabilities of local areas to respond and adapt to the health
      impacts at the local level.

PMID- 17185293
TI  - Emergency department overcrowding: analysis of the factors of renege rate.
AB  - BACKGROUND: Reneging (i.e., leaving without being seen) is an important outcome
      of emergency department (ED) overcrowding. The input-throughput-output
      conceptualization of ED patient flow is helpful in understanding and measuring
      the impact of various factors on this outcome. OBJECTIVES: To quantify the impact
      of input and output factors on ED renege rate. METHODS: The authors used patient
      level and system-level data from multiple sources in their institution to build
      logistic regression models, with reneging as the dependent variable. This
      approach provides the impact of each input and output factor on renege rate
      expressed as an odds ratio (OR). RESULTS: The OR for reneging attributable to the
      difference between the 80th and 20th percentile values for inpatient bed
      utilization is 1.05. Comparing 80th and 20th percentile values for boarded ED
      admits as of 7 AM, the OR is 1.73; for daily ED arrivals, the OR is 2.00; and for
      admission percentage, the OR is 1.12. The OR for evening versus morning patient
      arrival time is 3.9 and for patient arrival on a Monday versus a Sunday is 2.7.
      The OR for reneging for a patient presenting on Monday evening versus Sunday
      morning is 10.5. CONCLUSIONS: The effects of ED input and output factors on
      renege rate are significant and quantifiable. At least some of the variation in
      these factors and subsequently their effects are predictable, suggesting that
      further refinement in the management of ED and inpatient resources could affect
      improvement in ED renege rate. Continued efforts at quantifying the effects are
      warranted.

PMID- 17185294
TI  - The Society for Academic Emergency Medicine position on ethical relationships
      with the biomedical industry.

PMID- 17185295
TI  - Use of signal sequences as an in situ removable sequence element to stimulate
      protein synthesis in cell-free extracts.
AB  - This study developed a method to boost the expression of recombinant proteins in
      a cell-free protein synthesis system without leaving additional amino acid
      residues. It was found that the nucleotide sequences of the signal peptides serve
      as an efficient downstream box to stimulate protein synthesis when they were
      fused upstream of the target genes. The extent of stimulation was critically
      affected by the identity of the second codons of the signal sequences. Moreover,
      the yield of the synthesized protein was enhanced by as much as 10 times in the
      presence of an optimal second codon. The signal peptides were in situ cleaved and
      the target proteins were produced in their native sizes by carrying out the cell
      free synthesis reactions in the presence of Triton X-100, most likely through the
      activation of signal peptidase in the S30 extract. The amplification of the
      template DNA and the addition of the signal sequences were accomplished by PCR.
      Hence, elevated levels of recombinant proteins were generated within several
      hours.

PMID- 17185296
TI  - Use of high inoculum for early metabolic signalling and rapid susceptibility
      testing of Aspergillus species.
AB  - OBJECTIVES: To develop and evaluate a new method for rapid susceptibility testing
      of Aspergillus spp. based on early metabolic signalling of high-inoculum biomass.
      METHODS: Susceptibility to amphotericin B and voriconazole was studied in 39
      clinical isolates of Aspergillus spp. (16 Aspergillus fumigatus, 11 Aspergillus
      flavus, 12 Aspergillus terreus). At 6 or 8 h after inoculation for A. fumigatus
      and A. flavus, and at 8 or 12 h after inoculation for A. terreus, 100 microg/mL
      of the tetrazolium salt XTT and 25 microM menadione were added and absorbance
      measured at 450 nm after 2 h of incubation at 37 degrees C. Inocula used were
      10(6) conidia/mL for A. fumigatus and A. terreus and 10(5) conidia/mL for A.
      flavus, as lower inocula exhibited very low metabolic activity at these time
      points. Data were analysed with the sigmoid E(max) model and compared with visual
      (lowest drug concentration showing no growth) and spectrophotometric MIC
      determination at 48 h (CLSI M38-A method). RESULTS: The E(max) model described
      well the concentration-effect relationship for early metabolic activity and 48 h
      fungal biomass (median r(2): 0.97 and 0.93, respectively). Use of the model
      allowed characterization and quantification of species- and drug-related
      differences in pharmacological inhibition of early metabolic activity as well as
      calculation of appropriate cutoff levels for MIC determination with the XTT
      assay. Using these cutoff levels, for A. fumigatus and A. flavus at both time
      points (6 and 8 h) and for A. terreus at 12 h, the agreement (+/- one dilution)
      of the XTT assay with the CLSI method was 91-100% and its reproducibility was 97
      100%. CONCLUSIONS: This newly developed high-inoculum-based method provides rapid
      and reproducible MIC determinations for Aspergillus spp.

PMID- 17185297
TI  - Aspirin and ibuprofen enhance pyrazinamide treatment of murine tuberculosis.
AB  - OBJECTIVES: Aspirin (acetylsalicylic acid) or ibuprofen [2-(4-isobutyl-phenyl)
      propionic acid] was administered to mice undergoing treatment of tuberculosis
      infection with pyrazinamide to determine if these non-steroidal anti-inflammatory
      drugs (NSAIDs) enhance pyrazinamide activity in vivo. METHODS: BALB/c mice were
      infected with Mycobacterium tuberculosis H37Rv through aerosol exposure. Mice
      were treated orally with aspirin, ibuprofen or pyrazinamide, alone and in
      combination. The impact of daily administration of these drugs for 1 month was
      determined by enumerating viable bacteria in the lung and spleen. RESULTS:
      Aspirin or ibuprofen alone at 20 mg/kg per day had little effect on tuberculosis
      infection after 1 month of treatment, while pyrazinamide at 150 mg/kg per day led
      to a reduction of about 1.5 log(10) cfu in the lung and 2 log(10) cfu in the
      spleen compared with the control. Simultaneous administration of either aspirin
      or ibuprofen with pyrazinamide resulted in a further decrease of about 0.4
      log(10) cfu in the lung and more than 1 log(10) cfu in the spleen compared with
      mice receiving pyrazinamide alone. All spleens in the pyrazinamide-only treatment
      group were positive for infection. Of mice treated with both aspirin and
      pyrazinamide, two of five spleens were negative for colony formation, with a
      lower limit of detection of 0.90 log(10) cfu per organ. Three of five mice given
      ibuprofen and pyrazinamide had culture-negative spleens. CONCLUSIONS: Aspirin and
      ibuprofen enhance the effect of pyrazinamide during the initial phase of
      tuberculosis treatment in the mouse model. Further investigation is necessary to
      determine the impact of NSAIDs on long-term treatment with pyrazinamide and other
      antituberculosis drugs in the mouse model of tuberculosis infection and the
      clinical implications of these findings on tuberculosis treatment in humans.

PMID- 17185299
TI  - Emerging fluoroquinolone resistance in Neisseria meningitidis in India: cause for
      concern.

PMID- 17185298
TI  - Ertapenem in critically ill patients with early-onset ventilator-associated
      pneumonia: pharmacokinetics with special consideration of free-drug
      concentration.
AB  - OBJECTIVES: Most information about pharmacokinetics of antimicrobial agents is
      obtained from studies in healthy volunteers. However, antibiotics are
      therapeutically used in infected patients with very different pharmacokinetic
      properties compared with healthy individuals. PATIENTS AND METHODS: In a single
      centre, prospective, open-label study, 17 adult critically ill patients with
      early-onset ventilator-associated pneumonia (VAP) were treated with 1 g of
      ertapenem infusion once a day. Blood and urine samples were collected before and
      at different time-points up to 24 h after medication on day 1. Concentrations of
      ertapenem in plasma were determined with a validated HPLC method. Free-drug
      concentrations were estimated using a two-class binding site equation. RESULTS:
      The overall clinical success rate of the assessable cases was 66.7% (12/16).
      Pharmacokinetic parameters of ertapenem in our critically ill patients were
      clearly different when compared to those reported in the literature for healthy
      volunteers. The enhanced V(z) (17 vs. 8 L) and CL(TOT) (43 vs. 20 mL/min) with
      resulting lower C(max) (90 vs. 253 mg/L) and AUC(0-infinity) (418 vs. 817 mg x
      h/L) values were mainly related to hypoalbuminaemia (range 9.2-25.6 g/L) in our
      patient population. A population pharmacokinetic analysis using the NONMEM
      program indicated creatinine clearance as a significant covariate for explaining
      the between-subject variability of ertapenem in the patient population. Estimated
      free plasma concentrations of ertapenem exceeded a MIC(90) of 2 mg/L only for 6 h
      (25%) after infusion. CONCLUSIONS: For an adequate dose adjustment of highly
      protein-bound drugs like ertapenem, knowledge of actual albumin concentrations is
      necessary. A shortening of the dosage interval or continuous infusion of
      ertapenem should be considered to ensure optimal free concentrations in
      critically ill patients with severe hypoalbuminaemia and normal renal function.

PMID- 17185300
TI  - Multiplex PCR for rapid detection of genes encoding acquired metallo-beta
      lactamases.

PMID- 17185301
TI  - Botulinum toxin for writer's cramp: a randomised, placebo-controlled trial and 1
      year follow-up.
AB  - BACKGROUND: Botulinum toxin type A (BoNT-A) has become the treatment of choice
      for most types of focal dystonia. OBJECTIVE: To investigate the efficacy of BoNT
      A injections in patients with writer's cramp in a double-blind, randomised,
      placebo-controlled trial and to evaluate the follow-up results. METHODS: Forty
      participants were randomised to treatment with either BoNT-A or placebo
      injections in two sessions. Trial duration was 12 weeks. The primary outcome
      measure was the patients' choice to continue with the treatment, despite its
      possible disadvantages. Secondary outcome measures included several clinical
      rating scales on the levels of impairment and disability. Assessments were made
      at baseline and 2 months (secondary outcomes) and 3 months (primary outcome).
      Duration of follow-up was 1 year. RESULTS: 39 patients completed the trial.
      Fourteen of 20 patients (70%) receiving BoNT-A reported a beneficial effect and
      chose to continue treatment, versus 6 of 19 patients (31.6%) in the placebo group
      (p = 0.03). The changes on most of the clinical rating scales were significantly
      in favour of BoNT-A. Side effects reported were hand weakness, which was mostly
      mild and always transient, and pain at the injection site. After 1 year, 20 of 39
      patients were still under treatment with a positive effect. CONCLUSION: Treatment
      with BoNT-A injections led to a significantly greater improvement compared with
      placebo, according to patients' opinion and clinical assessment scales. Weakness
      in the hand is an important side effect of BoNT-A injections, but despite this
      disadvantage, most patients preferred to continue treatment. About 50% of our
      patients were still under treatment after 1 year.

PMID- 17185302
TI  - Predicting binge-drinking behaviour using an extended TPB: examining the impact
      of anticipated regret and descriptive norms.
AB  - AIMS: To investigate the utility of an extended Theory of Planned Behaviour
      (TPB), including descriptive norms and anticipated regret, in predicting binge
      drinking intentions and behaviour. METHODS: A total of 178 undergraduates
      completed a questionnaire containing measures of TPB variables, descriptive
      norms, anticipated regret, and previous binge-drinking behaviour. One week later,
      104 students completed a measure of binge-drinking behaviour. RESULTS:
      Hierarchical regression demonstrated that attitudes (beta = 0.30, P < 0.001) and
      anticipated regret (beta = 0.47, P < 0.001) were significant predictors of
      intentions, with the final equation accounting for 58% of the variance.
      Hierarchial regression found that intentions (beta = -0.21, P < 0.05) and
      previous binge-drinking behaviour (beta = 0.36, P < 0.01) predicted current
      drinking behaviour, accounting for 33% of the variance. CONCLUSIONS: The study
      suggests that modifying attitudes and inducing regret may be effective strategies
      for reducing binge-drinking intentions among undergraduates, which should reduce
      subsequent binge-drinking behaviour.

PMID- 17185303
TI  - Management of octogenarians hospitalized for heart failure in Euro Heart Failure
      Survey I.
AB  - AIMS: Here, the aim is to study the management of octogenarians hospitalized for
      heart failure in Euro Heart Failure Survey I. Heart Failure (HF) is common in
      older people and associated with poor outcome. METHODS AND RESULTS: We compared
      clinical characteristics, treatment, and short-term outcomes in 2780
      octogenarians (group A, median age 85 years) and in 7912 younger patients (group
      B, median age 69 years) enrolled in the Euro Heart Failure Survey I. There were
      37% males in group A vs. 59% in group B (P < 0.001). Co-morbidities were more
      common in group A. Ejection fraction was measured only in 38% in group A vs. 65%
      in group B (P < 0.001) and when measured was preserved in 50 vs. 40% (P < 0.001).
      In-hospital and 12 weeks follow-up mortality were, respectively, 13 vs. 5% (P <
      0.001) and 12 vs. 6% (P < 0.001) in groups A and B. Acute cardiac conditions and
      co-morbidity predicted mortality, whereas the use of angiotensin-converting
      enzyme inhibitor (ACE-I) and beta-blockers was associated with a better outcome.
      ACE-I and beta-blockers were used in 50 vs. 66% (P < 0.001) and 24 vs. 42% (P <
      0.001) in groups A and B, respectively, whereas diuretics, digitalis, and
      nitrates were more commonly used in octogenarians. CONCLUSION: Preserved systolic
      function, multiple co-morbidities, and high mortality are observed in
      octogenarians with HF. In these patients, cardiac function is assessed in only a
      minority and treatments known to improve prognosis in younger patients under
      utilized. Overall, the management of octogenarians with HF does not follow
      international guidelines.

PMID- 17185304
TI  - Myocardial deformation to determine transmurality of myocardial infarction.

PMID- 17185305
TI  - Psychological and clinical predictors of return to work after acute coronary
      syndrome.
AB  - AIMS: Resumption of paid employment following acute coronary syndrome (ACS) is an
      important indicator of recovery, but has not been studied extensively in the
      modern era of acute patient care. METHODS AND RESULTS: A total of 126 patients
      who had worked before hospitalization for ACS were studied with measures of
      previous clinical history, ACS type and severity, clinical management, and
      sociodemographic characteristics. Depressed mood (Beck Depression Inventory) and
      type D personality were measured 7-10 days following admission. Among them, 101
      (80.2%) had returned to work 12-13 months later. Failure to resume work was
      associated with cardiac factors on admission (heart failure, arrhythmia), cardiac
      complications during the intervening months, and depression scores during
      hospitalization. It was not related to age, gender, socioeconomic status, type of
      ACS, cardiac history, acute clinical management, or type D personality. In
      multivariate analysis, the likelihood of returning to work was negatively
      associated with depression, independently of clinical and demographic factors
      [adjusted odds ratio 0.90, CI 0.82-0.99, P=0.032]. CONCLUSION: Depressed mood
      measured soon after admission is a predictor of returning to work following ACS.
      The management of early depressed mood might promote the resumption of economic
      activity and enhance the quality of life of cardiac patients.

PMID- 17185306
TI  - Variable aetiologies contributing to the anaemia of systolic heart failure are
      important to individual patient management.

PMID- 17185308
TI  - Gamma-glutamyltransferase, leukotrienes, and cardiovascular risk.

PMID- 17185309
TI  - Heart failure in different occupational classes in Sweden.
AB  - AIMS: The link between low socioeconomic status (SES) and coronary heart disease
      (CHD) is well established, but there is a paucity of data whether a similar
      relation exists for heart failure (HF). METHODS AND RESULTS: A total of 6999 men
      47-55 years old, without a prior stroke or myocardial infarction, from a
      population sample of 9998 men, were investigated during 1970-73. Over a 28-year
      follow-up, 1004 men (14.3%) were discharged from hospital or died with a
      diagnosis of HF. There was an inverse relationship between SES, measured as an
      occupational class, and future risk of HF. Compared with men in the highest
      occupational class, men with intermediate non-manual occupations had a multiple
      adjusted hazard ratio (HR) of 1.28, 95% confidence interval (CI) 0.98-1.67, lower
      officials and foremen had an HR of 1.57 (1.22-2.03), semiskilled and skilled
      workers 1.48 (1.15-1.89), and unskilled workers 1.72 (1.34-2.20). Results were
      similar if only men with a principal diagnosis of HF (n=516) were considered,
      irrespective of whether a diagnosis of acute myocardial infarction or coronary
      revascularization had been recorded at any time. CONCLUSION: Low SES is an
      independent risk factor for long-term risk of HF in men.

PMID- 17185310
TI  - Natural radioactivity intake into wheat grown on fertilized farms in two
      districts of Pakistan.
AB  - The use of phosphate fertilizers on agricultural farms enhances gamma-ray
      activity concentration in the farms and therefore absorbed dose rates to the
      public. The most common natural radionuclides in fertilizer and soil are (40)K,
      (226)Ra and (232)Th. Agricultural farms at four locations in two districts in
      Pakistan consisting of saline and normal soils had been under fertilizer
      treatment for the past 30, 20, 10 and 0 y, therefore, natural radioactivity has
      been measured in soil samples from these sites to investigate the effect of
      fertilizers in soil and wheat grown in these sites. Radioactivity measured in
      soil of the sites under investigation was 550-644, 20-35 and 42-58 Bq kg(-1) for
      (40)K, (226)Ra and (232)Th, respectively. Wheat was grown in the farms and
      radioactivity transferred from soil to roots, shoots and grains was also
      measured. Relatively high natural radioactivity has been observed in the
      fertilized agricultural farms and in the wheat plants grown in these farms. From
      the total amount of an element uptaken in a plant, distribution of the element in
      different parts of the plant has been studied. The distribution of potassium was
      almost uniform in roots, shoots and grains of wheat; that of radium was different
      in the three parts of wheat; and that of thorium was almost equal in shoots and
      grains but quite large in the roots. Soils to grain transfer factors of the
      natural radionuclides have been determined as 3-4 x 10(-2) for (226)Ra, 2-3 x 10(
      2) for (232)Th and 17-20 x 10(-2) for (40)K. Annual doses of (40)K and (226)Ra
      received by intake of grain products have been estimated to lie within range
      while the dose received from intake of (232)Th is larger than the range specified
      in UNSCEAR report 2000.

PMID- 17185311
TI  - Computer simulation of strand break yields in plasmid pBR322: DNA damage
      following 125I decay.
AB  - This paper presents results of (125)I effects on plasmid pBR322 in aqueous
      solution, simulating the complete transport of Auger and X rays up to the
      chemical phase. In addition to new sampling algorithms, new electronic cross
      sections are included. Simulations were carried out both with (125)I, bound to
      plasmid, or free, in its vicinity. The influence of the hydroxyl radical
      scavenger dimethyl sulfoxyde (DMSO) has also been tested, underlying that, in
      naked DNA, double strand breaks (caused by the decay of bound (125)I) are mainly
      due to direct hits. The calculated yields of relaxation events (RE) and
      linearization events (LE) show good agreement with experimental ones: when (125)I
      is bound to the plasmid pBR322, 0.16 RE and 0.83 LE per decay (without DMSO) are
      then observed. Then, when 2 mol DMSO is added, RE and LE probabilities become
      0.22 and 0.76. The very light differences with those from literature could arise
      from experimental conditions.

PMID- 17185312
TI  - Calibration, performance and type testing of personal dosemeters used in ionising
      radiation applications in Greece.
AB  - Active Personal Dosemeters (APDs) are widely used in real-time personal
      dosimetry. Their performance, operational characteristics and limitations, as
      well as their calibration should be routinely checked to assure satisfactory
      operation and safe use. This study summarises the results of such type tests and
      calibrations performed in almost 4750 dosemeters at Ionising Radiation
      Calibration Laboratory (HIRCL) of Greek Atomic Energy Commission (GAEC). About
      13.8% of the pencil type and 4.3% of the electronic dosemeters were found to be
      out of limits of acceptable performance. For the pencil type dosemeters, the mean
      calibration factor (CF+/-SD) for high- and low-dose categories was found to be
      1.014+/-0.102 (range 0.793-1.458) and 0.995+/-0.059 (range 0.794-1.311),
      respectively. Of these >85% of them had reproducibility better than 90%, while
      <1% showed remarkable non-linearity and approximately 10% of them failed to
      retain the dose reading within the limits after 24 h. For the electronic
      dosemeters, the mean CF was 1.034+/-0.046 (range 0.967-1.238). The majority of
      them showed good reproducibility and linearity results while, after irradiation,
      the dose readings were not shifted through time. The energy response varies with
      the dosemeter type, reaching in one dosemeter type down to 50%. Both electronic
      and pencil did not showed electronic equilibrium problems.

PMID- 17185314
TI  - Presenting statistical uncertainty on cytogenetic dose estimates.
AB  - Cytogenetic dosimetry results are customarily accompanied by 95% confidence
      limits and the derivation of these limits is discussed. Simply presenting values
      of the best estimate of dose and 95% limits assumes that recipients of dosimetry
      reports, possibly the patients themselves, have a sufficient grasp of statistics
      to comprehend the concept of uncertainty. Two further methods have been developed
      to aid improved understanding for the lay person. The first method, particularly
      useful for suspected low doses, presents a simple odds ratio indicating that the
      results favour either zero dose or that suspected; for example, from an
      unexpected dose recorded on a badge. The second method, described fully here for
      the first time, uses a graphical illustration of a normalised distribution of
      dose so that one may visualise the area beneath a curve that represents the
      probability that the dose lies within various bounds.

PMID- 17185313
TI  - Bystander responses in three-dimensional cultures containing radiolabelled and
      unlabelled human cells.
AB  - Research on the radiation-induced bystander effect has been carried out mainly in
      2-D tissue culture systems. This study uses a 3-D model, wherein apparently
      normal human diploid fibroblasts (AG1522) are grown in a carbon scaffold, to
      investigate the induction of a G(1) checkpoint in bystander cells present
      alongside radiolabelled cells. Cultures were simultaneously pulse-labelled with
      (3)H-deoxycytidine ((3)HdC) to selectively irradiate a minor fraction of cells,
      and bromodeoxyuridine (BrdU) to identify the radiolabelled cells. After thorough
      washing of cultures, iododeoxyuridine (IdU) was administered to detect
      proliferating bystander cells. The cultures were harvested at various times
      thereafter, and cells were reacted with two monoclonal antibodies specific to
      IdU/BrdU or BrdU, respectively, stained with propidium iodide, and subjected to
      multi-parameter flow cytometry. Cell-cycle progression was followed in
      radiolabelled cells (BrdU(+)) that were chronically irradiated by low energy beta
      particles emitted by DNA-incorporated (3)H, and in unlabelled bystander cells
      (BrdU(-)) by a flow cytometry based cumulative labelling index assay. As
      expected, radiolabelled cells were delayed, in a dose-dependent manner, in G(2)
      and subsequently G(1). No delay occurred in progression of bystander cells
      through G(1), when the labelled cells were irradiated at dose rates up to 0.32 Gy
      h(-1).

PMID- 17185315
TI  - An electron microbeam cell-irradiation system at KIRAMS: performance and
      preliminary experiments.
AB  - An electron microbeam cell-irradiation (EMCI) system is now ready for routine
      operation in Korea. The system components include an electron gun operating at 1
      100 keV, a beam transport chamber delivering a micron-sized beam, a cell image
      acquisition and positioning part and an automatic system control section. The
      present choice of source beam energy is 30 keV so that the radiation impact is
      conveyed to the targeted cells with a minimum spatial dispersion. The beam is
      available at 5 microm in diameter now, but can be changed in the range of 1-200
      microm. The cellular dose is delivered with a standard deviation of 30% at 0.1
      Gy, 10% at 1 Gy and 3% at 10 Gy. The cells are recognised by over 98% in a 1 mm x
      1 mm area and the system is capable of irradiating up to 30,000 cells h(-1).

PMID- 17185316
TI  - Pancreas and beta-cell development: from the actual to the possible.
AB  - The development of insulin-producing pancreatic beta (beta)-cells represents the
      culmination of a complex developmental program. Cells of the posterior foregut
      assume a pancreatic identity, cells within the expanding pancreatic primordia
      adopt an endocrine fate, and a subset of these precursors becomes competent to
      generate beta-cells. Postnatally, beta-cells are primarily maintained by self
      duplication rather than new differentiation. Although major gaps in our knowledge
      still persist, experiments across several organisms have shed increasing light on
      the steps of beta-cell specification and differentiation. Increasing our
      understanding of the extrinsic, as well as intrinsic, mechanisms that control
      these processes should facilitate efforts to regenerate this important cell type
      in humans.

PMID- 17185317
TI  - Getting axons onto the right path: the role of transcription factors in axon
      guidance.
AB  - The normal function of the nervous system requires that the constituent neurons
      are precisely 'wired together'. During embryogenesis, each neuron extends an
      axonal process, which can navigate a considerable distance to its target.
      Although a number of the receptors and guidance signals that direct axonal growth
      have been identified, less is known about the transcription factors that regulate
      the expression of these molecules within the neuron and its environment. This
      review examines recent studies in vertebrates and Drosophila that address the
      identity of the transcription factors that either control the repertoire of
      guidance receptors and signals that permits an axon to take a particular
      trajectory or act themselves as novel extracellular guidance factors.

PMID- 17185318
TI  - Potency of testicular somatic environment to support spermatogenesis in XX/Sry
      transgenic male mice.
AB  - The sex-determining region of Chr Y (Sry) gene is sufficient to induce testis
      formation and the subsequent male development of internal and external genitalia
      in chromosomally female mice and humans. In XX sex-reversed males, such as XX/Sry
      transgenic (XX/Sry) mice, however, testicular germ cells always disappear soon
      after birth because of germ cell-autonomous defects. Therefore, it remains
      unclear whether or not Sry alone is sufficient to induce a fully functional
      testicular soma capable of supporting complete spermatogenesis in the XX body.
      Here, we demonstrate that the testicular somatic environment of XX/Sry males is
      defective in supporting the later phases of spermatogenesis. Spermatogonial
      transplantation analyses using XX/Sry male mice revealed that donor XY
      spermatogonia are capable of proliferating, of entering meiosis and of
      differentiating to the round-spermatid stage. XY-donor-derived round spermatids,
      however, were frequently detached from the XX/Sry seminiferous epithelia and
      underwent cell death, resulting in severe deficiency of elongated spermatid
      stages. By contrast, immature XY seminiferous tubule segments transplanted under
      XX/Sry testis capsules clearly displayed proper differentiation into elongated
      spermatids in the transplanted XY-donor tubules. Microarray analysis of
      seminiferous tubules isolated from XX/Sry testes confirmed the missing expression
      of several Y-linked genes and the alterations in the expression profile of genes
      associated with spermiogenesis. Therefore, our findings indicate dysfunction of
      the somatic tubule components, probably Sertoli cells, of XX/Sry testes,
      highlighting the idea that Sry alone is insufficient to induce a fully functional
      Sertoli cell in XX mice.

PMID- 17185319
TI  - Regulation of redox metabolism in the mouse oocyte and embryo.
AB  - Energy homeostasis of the oocyte is a crucial determinant of fertility. Following
      ovulation, the oocyte is exposed to the unique environment of the Fallopian tube,
      and this is reflected in a highly specialised biochemistry. The minute amounts of
      tissue available have made the physiological analysis of oocyte intermediary
      metabolism almost impossible. We have therefore used confocal imaging of
      mitochondrial and cytosolic redox state under a range of conditions to explore
      the oxidative metabolism of intermediary substrates. It has been known for some
      time that the early mouse embryo metabolises external pyruvate and lactate but
      not glucose to produce ATP. We now show at the level of single oocytes, that
      supplied glucose has no effect on the redox potential of the oocyte. Pyruvate is
      a cytosolic oxidant but a mitochondrial reductant, while lactate is a strong
      cytosolic reductant via the activity of lactate dehydrogenase. Unexpectedly,
      lactate-derived pyruvate appears to be diverted from mitochondrial oxidation. Our
      approach also reveals that the level of reduced glutathione (GSH) in the oocyte
      is maintained by glutathione reductase, which oxidises intracellular NADPH to
      reduce oxidised glutathione. Surprisingly, NADPH does not seem to be supplied by
      the pentose phosphate pathway in the unfertilised oocyte but rather by cytosolic
      NADP-dependent isocitrate dehydrogenase. Remarkably, we also found that the
      oxidant action of pyruvate impairs development, demonstrating the fundamental
      importance of redox state on early development.

PMID- 17185320
TI  - Antagonistic roles of full-length N-cadherin and its soluble BMP cleavage product
      in neural crest delamination.
AB  - During neural crest ontogeny, an epithelial to mesenchymal transition is
      necessary for cell emigration from the dorsal neural tube. This process is likely
      to involve a network of gene activities, which remain largely unexplored. We
      demonstrate that N-cadherin inhibits the onset of crest delamination both by a
      cell adhesion-dependent mechanism and by repressing canonical Wnt signaling
      previously found to be necessary for crest delamination by acting downstream of
      BMP4. Furthermore, N-cadherin protein, but not mRNA, is normally downregulated
      along the dorsal tube in association with the onset of crest delamination, and we
      find that this process is triggered by BMP4. BMP4 stimulates cleavage of N
      cadherin into a soluble cytoplasmic fragment via an ADAM10-dependent mechanism.
      Intriguingly, when overexpressed, the cytoplasmic N-cadherin fragment
      translocates into the nucleus, stimulates cyclin D1 transcription and crest
      delamination, while enhancing transcription of beta-catenin. CTF2 also rescues
      the mesenchymal phenotype of crest cells in ADAM10-inhibited neural primordia.
      Hence, by promoting its cleavage, BMP4 converts N-cadherin inhibition into an
      activity that is likely to participate, along with canonical Wnt signaling, in
      the stimulation of neural crest emigration.

PMID- 17185321
TI  - Rbf1-independent termination of E2f1-target gene expression during early
      Drosophila embryogenesis.
AB  - The initiation and maintenance of G1 cell cycle arrest is a key feature of animal
      development. In the Drosophila ectoderm, G1 arrest first appears during the
      seventeenth embryonic cell cycle. The initiation of G1(17) arrest requires the
      developmentally-induced expression of Dacapo, a p27-like Cyclin E-Cdk2 inhibitor.
      The maintenance of G1(17) arrest requires Rbf1-dependent repression of E2f1
      regulated replication factor genes, which are expressed continuously during
      cycles 1-16 when S phase immediately follows mitosis. The mechanisms that trigger
      Rbf1 repressor function and mediate G1(17) maintenance are unknown. Here we show
      that the initial downregulation of expression of the E2f1-target gene RnrS, which
      occurs during cycles 15 and 16 prior to entry into G1(17), does not require Rbf1
      or p27(Dap). This suggests a mechanism for Rbf1-independent control of E2f1
      during early development. We show that E2f1 protein is destroyed in a cell cycle
      dependent manner during S phase of cycles 15 and 16. E2f1 is destroyed during
      early S phase, and requires ongoing DNA replication. E2f1 protein reaccumulates
      in epidermal cells arrested in G1(17), and in these cells the induction of
      p27(Dap) activates Rbf1 to repress E2f1-target genes to maintain a stable G1
      arrest.

PMID- 17185323
TI  - Polycomb/Trithorax response elements and epigenetic memory of cell identity.
AB  - Polycomb/Trithorax group response elements (PRE/TREs) are fascinating chromosomal
      pieces. Just a few hundred base pairs long, these elements can remember and
      maintain the active or silent transcriptional state of their associated genes for
      many cell generations, long after the initial determining activators and
      repressors have disappeared. Recently, substantial progress has been made towards
      understanding the nuts and bolts of PRE/TRE function at the molecular level and
      in experimentally mapping PRE/TRE sites across whole genomes. Here we examine the
      insights, controversies and new questions that have been generated by this recent
      flood of data.

PMID- 17185322
TI  - Distinct Wnt signaling pathways have opposing roles in appendage regeneration.
AB  - In contrast to mammals, lower vertebrates have a remarkable capacity to
      regenerate complex structures damaged by injury or disease. This process, termed
      epimorphic regeneration, involves progenitor cells created through the
      reprogramming of differentiated cells or through the activation of resident stem
      cells. Wnt/beta-catenin signaling regulates progenitor cell fate and
      proliferation during embryonic development and stem cell function in adults, but
      its functional involvement in epimorphic regeneration has not been addressed.
      Using transgenic fish lines, we show that Wnt/beta-catenin signaling is activated
      in the regenerating zebrafish tail fin and is required for formation and
      subsequent proliferation of the progenitor cells of the blastema. Wnt/beta
      catenin signaling appears to act upstream of FGF signaling, which has recently
      been found to be essential for fin regeneration. Intriguingly, increased Wnt/beta
      catenin signaling is sufficient to augment regeneration, as tail fins regenerate
      faster in fish heterozygous for a loss-of-function mutation in axin1, a negative
      regulator of the pathway. Likewise, activation of Wnt/beta-catenin signaling by
      overexpression of wnt8 increases proliferation of progenitor cells in the
      regenerating fin. By contrast, overexpression of wnt5b (pipetail) reduces
      expression of Wnt/beta-catenin target genes, impairs proliferation of progenitors
      and inhibits fin regeneration. Importantly, fin regeneration is accelerated in
      wnt5b mutant fish. These data suggest that Wnt/beta-catenin signaling promotes
      regeneration, whereas a distinct pathway activated by wnt5b acts in a negative
      feedback loop to limit regeneration.

PMID- 17185324
TI  - Efficacy of infliximab on MRI-determined bone oedema in psoriatic arthritis.
AB  - BACKGROUND: Psoriatic arthritis (PsA) is commonly associated with bone pathology,
      including entheseal new bone formation and osteolysis. On MRI, areas of active
      clinical involvement are represented by bone oedema and synovitis. AIM: To assess
      the impact of infliximab on bone oedema in PsA as shown by MRI. METHODS: 18
      patients with joint swelling, psoriasis and seronegativity for rheumatoid factor
      received four infusions of infliximab, 3 mg/kg, in combination with methotrexate.
      MRI of the affected hand (12 patients) or knee joints (6 patients) was performed
      before and after treatment. The primary outcome was the assessment of bone oedema
      and synovitis at 20 weeks as shown by MRI. Secondary outcomes included the
      American College of Rheumatology (ACR) response criteria, psoriasis skin scores
      (Psoriasis Area and Severity Index (PASI)) and a quality of life measure
      (Psoriatic Arthritis Quality of Life (PsAQoL)). RESULTS: At baseline, bone oedema
      was seen in 50% of patients (seven hands and two knees) in 30% of scanned joints,
      and this improved or resolved in all cases in the hand joints (p = 0.018) and in
      one knee joint at 20 weeks. Synovitis was found to be reduced in 90% of cases on
      MRI. Likewise, a significant improvement in all clinical outcomes, including PASI
      (p = 0.003) and PsAQoL (p = 0.006) was seen at week 20. 65% (n = 11) of the
      patients achieved an ACR response, of whom 45% had ACR70 or above and 54% had
      ACR20 or ACR50. CONCLUSIONS: Infliximab treatment is associated with dramatic
      improvements in MRI-determined bone oedema in PsA in the short term. It remains
      to be determined whether infliiximib treatment is the cause for prevention of new
      bone formation, bone fusion or osteolysis in PsA as shown by radiography.

PMID- 17185326
TI  - High-resolution ultrasonography of the first metatarsal phalangeal joint in gout:
      a controlled study.
AB  - OBJECTIVE: To compare high-resolution ultrasound (HRUS) with conventional
      radiography in the detection of erosions in the first metatarsophalangeal joints
      (1st MTPJs) of patients with gout and to identify the characteristic sonographic
      features of gout. METHODS: HRUS examination of the 1st MTPJs of both feet was
      performed by two independent sonographers. The presence of joint and soft-tissue
      pathology was recorded. x Ray examination of the feet was performed on the same
      day and reported by the same radiologist. RESULTS: 39 male patients with gout and
      22 age-matched control subjects (14 with an inflammatory arthropathy and 8
      disease free) were studied. The agreement on erosion between HRUS and x ray was
      poor, kappa = 0.229 (non-weighted), with McNemar's test being significant
      (p<0.001) indicating a large number of false negative x rays. 22 MTPJs in
      patients with gout had never been subjected to a clinical attack of acute gout.
      In these MTPJs, there were 10 erosions detected by HRUS and 3 erosions on x ray.
      HRUS features significantly more prevalent in the patients with gout were hard
      and soft tophus-like lesions (p<0.01) and the double contour sign (p<0.01).
      CONCLUSIONS: These data show that HRUS may assist in the management of gout in
      two ways: first, by aiding in the diagnosis by identifying the sonographic
      features that may be representative of the disease, and, second, by allowing the
      early detection of erosive joint damage and/or tophaceous deposits even in
      clinically silent joints.

PMID- 17185325
TI  - Decreased B cell activating factor receptor expression on peripheral lymphocytes
      associated with increased disease activity in primary Sjogren's syndrome and
      systemic lupus erythematosus.
AB  - OBJECTIVE: To analyse B cell activating factor (BAFF) receptor (BAFF-R)
      expression on peripheral lymphocytes from patients with primary Sjogren's
      syndrome (pSS) and systemic lupus erythematosus (SLE). PATIENTS AND METHODS:
      Peripheral blood mononuclear cells from 20 patients with pSS, 19 patients with
      SLE and 15 controls were examined by flow cytometry to investigate BAFF-R mean
      fluorescence intensity (MFI) on lymphocytes. BAFF-R mRNA level from isolated
      blood B cells of nine patients with pSS and eight controls was assessed by real
      time quantitative reverse transcription-PCR. BAFF serum level was determined by
      ELISA. RESULTS: In all subjects, BAFF-R was expressed on all naive CD27- and
      memory CD27+ B-cells and was present on <0.5% of T cells. The expression of BAFF
      R on B cells was significantly decreased in patients with pSS as compared with
      controls (MFI = 7.8 vs 10.6, p = 0.001), and was intermediate in patients with
      SLE (MFI = 9.5). Serum BAFF level was inversely correlated with BAFF-R MFI (p =
      0.007), but not because of competition between endogenous BAFF (at observed
      concentrations in patients) and the monoclonal antibody (11C1) detecting BAFF-R.
      BAFF-R mRNA levels did not differ between patients with pSS and controls (p =
      0.48). BAFF-R MFI decreased after overnight culture with recombinant human BAFF
      (from 32.5 to 25.4, p = 0.03). Contrary to the serum BAFF level, BAFF-R
      expression was correlated with extraglandular involvement in pSS and SLE Disease
      Activity Index. CONCLUSIONS: BAFF-R expression is reduced on peripheral B cells
      of patients with pSS and SLE. This down-regulation occurs through a post
      transcriptional mechanism and could be the consequence of chronic increase in
      BAFF. BAFF-R levels on B cells could be a novel activity biomarker in autoimmune
      diseases.

PMID- 17185327
TI  - Persistence of interleukin 7 activity and levels on tumour necrosis factor alpha
      blockade in patients with rheumatoid arthritis.
AB  - OBJECTIVES: To identify the mechanism of interleukin (IL)7-stimulated tumour
      necrosis factor alpha (TNFalpha) production and to determine the relationship
      between intra-articular IL7 and TNFalpha expression levels in patients with
      rheumatoid arthritis (RA). In addition, the effect of TNFalpha blockade on IL7
      activity and on IL7 levels was studied. METHODS: The effect of IL7 on isolated
      CD4 T cells and CD14 monocytes/macrophages was studied. IL7 and TNFalpha levels
      were measured in the synovial fluid of patients with RA. In RA synovial tissue,
      IL7 and TNFalpha expression was assessed in addition to IL1beta, numbers of
      inflammatory cells and adhesion molecule expression. The extent to which TNFalpha
      blockade could prevent IL7-induced lymphocyte responses was studied in vitro. In
      addition, regulation of serum IL7 levels on anti-TNFalpha therapy (adalimumab)
      was studied. RESULTS: IL7 induced cell contact-dependent TNFalpha production by
      cocultures of T cells and monocytes, but not by T cells and monocytes cultured
      separately. IL7 and TNFalpha levels in RA synovial fluid and synovial tissue
      significantly correlated. IL7-stimulated lymphocyte responses were not inhibited
      by TNFalpha blockade. Circulating IL7 levels were significantly reduced in
      patients who successfully responded to anti-TNFalpha treatment. However, IL7
      levels persisted in non-responders. CONCLUSION: The present data suggest that IL7
      is an important inducer of T cell-dependent TNFalpha production in RA joints.
      This may contribute to the correlation of intra-articular IL7 and TNFalpha in
      these joints. Furthermore, the persistence of IL7-induced inflammatory activity
      on TNFalpha blockade in vitro and persistence of IL7 levels and disease activity
      in anti-TNFalpha non-responders suggest that IL7 might additionally promote
      TNFalpha-independent inflammation.

PMID- 17185328
TI  - Job related affective well-being among primary health care physicians.
AB  - BACKGROUND: Job related affective well-being is important for a healthy life and
      job satisfaction for all individuals, including physicians. The later group,
      however, is most often compromised. OBJECTIVES: We aimed to investigate a group
      of Turkish primary health care physicians' job related emotional perceptions and
      to assess their reactions in terms of stress, anxiety and depression. METHODS: A
      descriptive, cross-sectional, self-reported questionnaire study was conducted. A
      total of 60 primary health care centres and 274 general practitioners who were
      working at these centres participated in the study. The response rate was 74%.
      Printed questionnaires were completed by the participants anonymously. We used
      the Job Related Affective Well-Being Scale (JAWS) and Depression Anxiety Stress
      Scale (DASS 42). Correlation analysis and hierarchic regression were performed.
      RESULTS: Correlations between JAWS and DASS total scores were negative and
      statistically significant (r = -0.52; P< 0.01). Low pleasure/high arousal (LPHA)
      and low pleasure/low arousal (LPLA) variations that describe negative emotional
      states show a positive and significant relationship with depression, anxiety and
      stress values. The highest mean score was obtained for the high pleasure/low
      arousal (HPLA) status that can be interpreted to mean that our study group was
      pleased with their job but was not motivated. CONCLUSIONS: Physician's job
      related negative emotional perceptions are associated with reactions in terms of
      stress, anxiety and depression. For this reason, it is critical to consider
      primary care physicians' job related affectations and job related stimuli.

PMID- 17185329
TI  - Does ambivalence about becoming pregnant explain social class differentials in
      use of contraception?
AB  - BACKGROUND: Manual social class background has consistently been associated with
      markers of poorer sexual health. This study of adults examines contraceptive use
      across social classes and the role of ambiguity towards pregnancy in non-use.
      METHOD: A nationally representative sample of Irish men and women aged 18-45
      years were surveyed (n = 3317). Use of contraception in the last year and at the
      last occasion of vaginal sexual intercourse was queried. Reasons for non-use were
      examined. RESULTS: The consistency of contraceptive use in the last year was
      higher among women than men with lower use in unskilled manual social classes for
      both sexes. 'Not having planned for sex' was the most commonly cited reason for
      non-use (47% of men and 40% of women). 'Not caring if pregnancy occurred' was
      cited by 11% of women and 12% of men, while 'took a chance' was cited by 8% of
      both men and women. Results showed semi and unskilled manual women more likely to
      report that sex was unplanned or that they 'took a chance'. Among men, all other
      classes were more likely to report each of the ambivalence statements than the
      professional and managerial class. CONCLUSIONS: The study provides evidence of
      social class differentials in use of contraception among adults, and shows that
      these may be due, in part, to higher levels of ambivalence about pregnancy among
      working class women. The article adds to the socio-demographic literature on
      class differentials in unwanted pregnancy and extends research on adolescents to
      cover patterns for adult women and men.

PMID- 17185331
TI  - Pain TRP-ed up by PARs.

PMID- 17185330
TI  - Sustained activation of proton channels and NADPH oxidase in human eosinophils
      and murine granulocytes requires PKC but not cPLA2 alpha activity.
AB  - The prevailing hypothesis that a signalling pathway involving cPLA(2)alpha is
      required to enhance the gating of the voltage-gated proton channel associated
      with NADPH oxidase was tested in human eosinophils and murine granulocytes. This
      hypothesis invokes arachidonic acid (AA) liberated by cPLA(2)alpha as a final
      activator of proton channels. In human eosinophils studied in the perforated
      patch configuration, phorbol myristate acetate (PMA) stimulation elicited NADPH
      oxidase-generated electron current (I(e)) and enhanced proton channel gating
      identically in the presence or absence of three specific cPLA(2)alpha inhibitors,
      Wyeth-1, pyrrolidine-2 and AACOCF(3) (arachidonyl trifluoromethyl ketone). In
      contrast, PKC inhibitors GFX (GF109203X) or staurosporine prevented the
      activation of either proton channels or NADPH oxidase. PKC inhibition during the
      respiratory burst reversed the activation of both molecules, suggesting that
      ongoing phosphorylation is required. This effect of GFX was inhibited by okadaic
      acid, implicating phosphatases in proton channel deactivation. Proton channel
      activation by AA was partially reversed by GFX or staurosporine, indicating that
      AA effects are due in part to activation of PKC. In granulocytes from mice with
      the cPLA(2)alpha gene disrupted (knockout mice), PMA or fMetLeuPhe activated
      NADPH oxidase and proton channels in a manner indistinguishable from the
      responses of control cells. Thus, cPLA(2)alpha is not essential to activate the
      proton conductance or for a normal respiratory burst. Instead, phosphorylation of
      the proton channel or an activating molecule converts the channel to its
      activated gating mode. The existing paradigm for regulation of the concerted
      activity of proton channels and NADPH oxidase must be revised.

PMID- 17185332
TI  - Voltage-dependent calcium channels of dog basilar artery.
AB  - Electrophysiological and molecular characteristics of voltage-dependent calcium
      (Ca(2+)) channels were studied using whole-cell patch clamp, polymerase chain
      reaction and Western blotting in smooth muscle cells freshly isolated from dog
      basilar artery. Inward currents evoked by depolarizing steps from a holding
      potential of -50 or -90 mV in 10 mm barium consisted of low- (LVA) and high
      voltage activated (HVA) components. LVA current comprised more than half of total
      current in 24 (12%) of 203 cells and less than 10% of total current in 52 (26%)
      cells. The remaining cells (127 cells, 62%) had LVA currents between one tenth
      and one half of total current. LVA current was rapidly inactivating, slowly
      deactivating, inhibited by high doses of nimodipine and mibefradil (> 0.3
      microM), not affected by omega-agatoxin GVIA (gamma100 nM), omega-conotoxin IVA
      (1 microM) or SNX-482 (200 nM) and probably carried by T-type Ca(2+) channels
      based on the presence of messenger ribonucleic acid (mRNA) and protein for
      Ca(v3.1) and Ca(v3.3) alpha(1) subunits of these channels. LVA currents exhibited
      window current with a maximum of 13% of the LVA current at -37.4 mV. HVA current
      was slowly inactivating and rapidly deactivating. It was inhibited by nimodipine
      (IC(50) = 0.018 microM), mibefradil (IC(50) = 0.39 microM) and omega-conotoxin IV
      (1 microM). Smooth muscle cells also contained mRNA and protein for L- (Ca(v1.2)
      and Ca(v1.3)), N- (Ca(v2.2)) and T-type (Ca(v3.1) and Ca(v3.3)) alpha(1) Ca(2+)
      channel subunits. Confocal microscopy showed Ca(v1.2) and Ca(v1.3) (L-type),
      Ca(v2.2) (N-type) and Ca(v3.1) and Ca(v3.3) (T-type) protein in smooth muscle
      cells. Relaxation of intact arteries under isometric tension in vitro to
      nimodipine (1 microM) and mibefradil (1 microM) but not to omega-agatoxin GVIA
      (100 nM), omega-conotoxin IVA (1 microM) or SNX-482 (1 microM) confirmed the
      functional significance of L- and T-type voltage-dependent Ca(2+) channel
      subtypes but not N-type. These results show that dog basilar artery smooth muscle
      cells express functional voltage-dependent Ca(2+) channels of multiple types.

PMID- 17185333
TI  - Tryptophan-scanning mutagenesis in the S1 domain of mammalian HCN channel reveals
      residues critical for voltage-gated activation.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are essential
      regulators in rhythmic activity, membrane excitability and synaptic transmission.
      There are four subtypes in mammals (HCN1-4); HCN4 has the slowest activation
      kinetics and HCN1 the fastest. Although voltage gating originates with the
      voltage-dependent motion of the S4 segment, the different activation kinetics
      between HCN1 and HCN4 are generated mainly by S1 and the S1-S2 loop. In this
      study, we investigate the structural basis of the ability of S1 to affect
      activation kinetics by replacing each individual S1 residue in HCN1 with a
      tryptophan (Trp) residue, a Trp perturbation scan. Robust currents were generated
      in 11 out of 19 Trp mutants. Hyperpolarization-activated currents were not
      detected in four mutants, and two other mutants generated only small currents.
      Presence or absence of current reflected the predicted alpha-helical structure of
      the S1 transmembrane segment. Tryptophan replacements of residues responsible for
      the different kinetics between HCN1 and HCN4 made the activation kinetics slower
      than the wild-type HCN1. Tryptophan mutations introduced in the middle of S1
      (L139W and V143W) prevented normal channel closure. Furthermore, a negatively
      charged residue at position 139 (L139D) induced a positive voltage shift of
      activation by 125 mV. Thus, L139 and V143 probably face a mobile part of the S4
      voltage sensor and may interact with it. These results suggest that the secondary
      structure of S1 is alpha-helical and profoundly affects the motion of the voltage
      sensor.

PMID- 17185334
TI  - Reversed somatodendritic I(h) gradient in a class of rat hippocampal neurons with
      pyramidal morphology.
AB  - In CA1 and neocortical pyramidal neurons, I(h) is present primarily in the
      dendrites. We asked if all neurons of a pyramidal morphology have a similar
      density of I(h). We characterized a novel class of hippocampal neurons with
      pyramidal morphology found in the stratum radiatum, which we termed the
      'pyramidal-like principal' (PLP) neuron. Morphological similarities to pyramidal
      neurons were verified by filling the neurons with biocytin. PLPs did not stain
      for markers associated with interneurons, and projected to both the septum and
      olfactory bulb. By using cell-attached patch-clamp recordings, we found that
      these neurons expressed a high density of I(h) in the soma that declined to a
      lower density in the dendrites, a pattern that is reversed compared to pyramidal
      neurons. The voltage-dependent activation and activation time constants of I(h)
      in the PLPs were similar to pyramidal neurons. Whole-cell patch-clamp recordings
      from the soma and dendrites of PLP neurons showed no significant differences in
      input resistance and local temporal summation between the two locations. Blockade
      of I(h) by ZD7288 increased the input resistance and temporal summation of
      simulated EPSPs, as in pyramidal neurons. When NMDA receptors were blocked,
      temporal summation at the soma of distal synaptic potentials was similar to that
      seen with current injections at the soma, suggesting a 'normalization' of
      temporal summation similar to that observed in pyramidal neurons. Thus, we have
      characterized a principal neuronal subtype in the hippocampus with a similar
      morphology but reversed I(h) somatodendritic gradient to that previously observed
      in CA1 hippocampal and neocortical pyramidal neurons.

PMID- 17185335
TI  - Parallel activation of mitochondrial oxidative metabolism with increased cardiac
      energy expenditure is not dependent on fatty acid oxidation in pigs.
AB  - Steady state concentrations of ATP and ADP in vivo are similar at low and high
      cardiac workloads; however, the mechanisms that regulate the activation of
      substrate metabolism and oxidative phosphorylation that supports this stability
      are poorly understood. We tested the hypotheses that (1) there is parallel
      activation of mitochondrial and cytosolic dehydrogenases in the transition from
      low to high workload, which increases NADH/NAD+ ratio in both compartments, and
      (2) this response does not require an increase in fatty acid oxidation (FAO).
      Anaesthetized pigs were subjected to either sham treatment, or an abrupt increase
      in cardiac workload for 5 min with dobutamine infusion and aortic constriction.
      Myocardial oxygen consumption and FAO were increased 3- and 2-fold, respectively,
      but ATP and ADP concentrations did not change. NADH-generating pathways were
      rapidly activated in both the cytosol and mitochondria, as seen in a 40%
      depletion in glycogen stores, a 3.6-fold activation of pyruvate dehydrogenase,
      and a 50% increase in tissue NADH/NAD+. Simulations from a multicompartmental
      computational model of cardiac energy metabolism predicted that parallel
      activation of glycolysis and mitochondrial metabolism results in an increase in
      the NADH/NAD+ ratio in both cytosol and mitochondria. FAO was blocked by 75% in a
      third group of pigs, and a similar increase in and the NAHD/NAD+ ratio was
      observed. In conclusion, in the transition to a high cardiac workload there is
      rapid parallel activation of substrate oxidation that results in an increase in
      the NADH/NAD+ ratio.

PMID- 17185336
TI  - Propagation of the cardiac impulse in the diabetic rat heart: reduced conduction
      reserve.
AB  - Diabetes mellitus is a growing epidemic with severe cardiovascular complications.
      Although much is known about mechanical and electrical cardiac dysfunction in
      diabetes, few studies have investigated propagation of the electrical signal in
      the diabetic heart and the associated changes in intercellular gap junctions.
      This study was designed to investigate these issues, using hearts from control
      and diabetic rats. Diabetic conditions were induced by streptozotocin (STZ),
      given i.v. 7-14 days before experiments. Optical mapping with the voltage
      sensitive dye di-4-ANEPPS, using hearts perfused on a Langendorff apparatus,
      showed little change in baseline conduction velocity in diabetic hearts,
      reflecting the large reserve of function. However, both the gap junction
      uncoupler heptanol (0.5-1 mM) and elevated potassium (9 mM, to reduce cell
      excitability) produced a significantly greater slowing of impulse propagation in
      diabetic hearts than in controls. The maximal action potential upstroke velocity
      (an index of the sodium current) and resting potential was similar in single
      ventricular myocytes from control and diabetic rats, suggesting similar
      electrical excitability. Immunoblotting of connexin 43 (Cx43), a major gap
      junction component, showed no change in total expression. However,
      immunofluorescence labelling of Cx43 showed a significant redistribution,
      apparent as enhanced Cx43 lateralization. This was quantified and found to be
      significantly larger than in control myocytes. Labelling of two other gap
      junction proteins, N-cadherin and beta-catenin, showed a (partial) loss of co
      localization with Cx43, indicating that enhancement of lateralized Cx43 is
      associated with non-functional gap junctions. In conclusion, conduction reserve
      is smaller in the diabetic heart, priming it for impaired conduction upon further
      challenges. This can desynchronize contraction and contribute to
      arrhythmogenesis.

PMID- 17185337
TI  - Tonic activation of NMDA receptors by ambient glutamate of non-synaptic origin in
      the rat hippocampus.
AB  - In several neuronal types of the CNS, glutamate and GABA receptors mediate a
      persistent current which reflects the presence of a low concentration of
      transmitters in the extracellular space. Here, we further characterize the tonic
      current mediated by ambient glutamate in rat hippocampal slices. A tonic current
      of small amplitude (53.99 +/- 6.48 pA at +40 mV) with the voltage dependency and
      the pharmacology of NMDA receptors (NMDARs) was detected in virtually all
      pyramidal cells of the CA1 and subiculum areas. Manipulations aiming at
      increasing D-serine or glycine extracellular concentrations failed to modify this
      current indicating that the glycine binding sites of the NMDARs mediating the
      tonic current were saturated. In contrast, non-transportable inhibitors of
      glutamate transporters increased the amplitude of this tonic current, indicating
      that the extracellular concentration of glutamate primarily regulates its
      magnitude. Neither AMPA/kainate receptors nor metabotropic glutamate receptors
      contributed significantly to this tonic excitation of pyramidal neurons. In the
      presence of glutamate transporter inhibitors, however, a significant proportion
      of the tonic conductance was mediated by AMPA receptors. The tonic current was
      unaffected when inhibiting vesicular release of transmitters from neurons but was
      increased upon inhibition of the enzyme converting glutamate in glutamine in
      glial cells. These observations indicate that ambient glutamate is mainly of
      glial origin. Finally, experiments with the use-dependent antagonist MK801
      indicated that NMDARs mediating the tonic conductance are probably extra-synaptic
      NMDARs.

PMID- 17185338
TI  - Mechanical load plays little role in contraction-mediated glucose transport in
      mouse skeletal muscle.
AB  - The factors responsible for control of glucose transport during exercise are not
      fully understood. We investigated the role of mechanical load in contraction
      mediated glucose transport in an isolated muscle preparation. Mouse extensor
      digitorum longus muscles were stimulated with repeated contractions for 10 min
      with or without N-benzyl-p-toluene sulphonamide (BTS, an inhibitor of myosin II
      ATPase) to block crossbridge activity. BTS inhibited force production during
      repeated contraction to approximately 5% of control. In contrast, BTS had little
      effect on glucose transport in the basal state (control = 0.55 +/- 0.04; BTS =
      0.47 +/- 0.09 micromol (20 min)(-1) ml(-1)) or after contraction (control = 2.27
      +/- 0.15; BTS = 2.10 +/- 0.16 micromol (20 min)(-1) ml(-1)). BTS did not
      significantly alter the contraction-mediated changes in high-energy phosphates,
      glutathione status (a measure of oxidant status) or AMP-activated protein kinase
      activity. In conclusion, these data show that mechanical load plays little role
      in contraction-mediated glucose transport. Instead, it is likely that the
      increased glucose transport during contraction is a consequence of the increase
      in myoplasmic Ca(2+) and the subsequent alterations in metabolism, e.g. increased
      energy turnover and production of reactive oxygen species.

PMID- 17185339
TI  - Evidence for association of GABA(B) receptors with Kir3 channels and regulators
      of G protein signalling (RGS4) proteins.
AB  - Many neurotransmitters and hormones signal by stimulating G protein-coupled
      neurotransmitter receptors (GPCRs), which activate G proteins and their
      downstream effectors. Whether these signalling proteins diffuse freely within the
      plasma membrane is not well understood. Recent studies have suggested that direct
      protein-protein interactions exist between GPCRs, G proteins and G protein-gated
      inwardly rectifying potassium (GIRK or Kir3) channels. Here, we used fluorescence
      resonance energy transfer (FRET) combined with total internal reflection
      fluorescence microscopy to investigate whether proteins within this signalling
      pathway move within 100 A of each other in the plasma membrane of living cells.
      GABA(B) R1 and R2 receptors, Kir3 channels, Galphao subunits and regulators of G
      protein signalling (RGS4) proteins were each fused to cyan fluorescent protein
      (CFP) or yellow fluorescent protein (YFP) and first assessed for functional
      expression in HEK293 cells. The presence of the fluorophore did not significantly
      alter the signalling properties of these proteins. Possible FRET was then
      investigated for different protein pair combinations. As a positive control, FRET
      was measured between tagged GABA(B) R1 and R2 subunits ( approximately 12% FRET),
      which are known to form heterodimers. We measured significant FRET between tagged
      RGS4 and GABA(B) R1 or R2 subunits ( approximately 13% FRET), and between Galphao
      and GABA(B) R1 or R2 subunits ( approximately 10% FRET). Surprisingly, FRET also
      occurred between tagged Kir3.2a/Kir3.4 channels and GABA(B) R1 or R2 subunits (
      approximately 10% FRET). FRET was not detected between Kir3.2a and RGS4 nor
      between Kir3.2a and Galphao. These data are discussed in terms of a model in
      which GABA(B) receptors, G proteins, RGS4 proteins and Kir3 channels are closely
      associated in a signalling complex.

PMID- 17185340
TI  - Changes in EMG coherence between long and short thumb abductor muscles during
      human development.
AB  - In adults, motoneurone pools of synergistic muscles that act around a common
      joint share a common presynaptic drive. Common drive can be revealed by both time
      domain and frequency domain analysis of EMG signals. Analysis in the frequency
      domain reveals significant coherence in the range 1-45 Hz, with maximal coherence
      in low (1-12 Hz) and high (16-32 Hz) ranges. The high-frequency range depends on
      cortical drive to motoneurones and is coherent with cortical oscillations at
      approximately 20 Hz frequencies. It is of interest to know whether oscillatory
      drive to human motoneurone pools changes with development. In the present study
      we examined age-related changes in coherence between rectified surface EMG
      signals recorded from the short and long thumb abductor muscles during steady
      isometric contraction obtained while subjects abducted the thumb against a
      manipulandum. We analysed EMG data from 36 subjects aged between 4 and 14 years,
      and 11 adult subjects aged between 22 and 59 years. Using the techniques of
      pooled coherence analysis and the chi(2) difference of coherence test we
      demonstrate that between the ages of 7 and 9 years, and 12 and 14 years, there
      are marked increases in the prevalence and magnitude of coherence at frequencies
      between 11 and 45 Hz. The data from subjects aged 12-14 years were similar to
      those obtained from adult controls. The most significant differences between
      younger children and the older age groups were detected at frequencies close to
      20 Hz. We believe that these are the first reported results demonstrating
      significant late maturational changes in the approximately 20 Hz common
      oscillatory drive to human motoneurone pools.

PMID- 17185341
TI  - Non-human primate fetal kidney transcriptome analysis indicates mammalian target
      of rapamycin (mTOR) is a central nutrient-responsive pathway.
AB  - Developmental programming is defined as the process by which gene-environment
      interaction in the developing organism leads to permanent changes in phenotype
      and function. Numerous reports of maternal nutrient restriction during pregnancy
      demonstrate altered renal development. Typically this alteration manifests as a
      reduction in the total number of glomeruli in the mature kidney of the offspring,
      and suggests that predisposition to develop chronic renal disease may include an
      in utero origin. In a previous study, we defined the transcriptome in the kidney
      from fetuses of control (CON, fed ad libitum) and nutrient-restricted (NR, fed
      70% of CON starting at 0.16 gestation (G)) pregnancies at half-way through
      gestation (0.5G), and established transcriptome and morphological changes in NR
      kidneys compared to CON. One goal of the present study was to use transcriptome
      data from fetal kidneys of CON and NR mothers at 0.5G with histological data to
      identify the molecular mechanisms that may regulate renal development. A second
      goal was to identify mechanisms by which NR elicits its affect on fetal baboon
      kidney. We have used an end-of-pathway gene expression analysis to prioritize and
      identify key pathways regulating the 0.5G kidney phenotype in response NR. From
      these data we have determined that the mammalian target of rapamycin (mTOR)
      signalling pathway is central to this phenotype.

PMID- 17185342
TI  - Genioglossus premotoneurons and the negative pressure reflex in rats.
AB  - Reflex increases in genioglossus (GG) muscle activity in response to negative
      pharyngeal pressure are important for maintenance of upper airway patency in
      humans. However, little is known of the central circuitry that mediates this
      negative pressure reflex (NPR). We used two approaches to determine which GG
      premotoneurons relay negative pressure-related information to the hypoglossal
      motor nucleus. First, to identify GG premotoneurons, we injected pseudorabies
      virus (PRV152) into the GG muscle. We found that medullary GG premotoneurons were
      concentrated mainly in the reticular formation adjacent to the hypoglossal motor
      nucleus. Second, in order to determine whether these perihypoglossal neurons were
      involved in the NPR, we quantified GG EMG responses to negative pressure applied
      to the isolated upper airway in anaesthetized rats before and after
      microinjection of muscimol (9 nl; 0.25 mM), a GABA-A receptor agonist, into the
      perihypoglossal premotor field. Pressures as low as -4 cm H(2)O increased
      inspiratory phase-related GG activity. The NPR was abolished following bilateral
      injections of muscimol into the perihypoglossal premotor field at and up to 500
      mum rostral to the obex. Muscimol in this location also increased the amplitude
      of basal, unstimulated phasic GG activity. By contrast, inhibition of neurons
      caudal to the obex decreased phasic GG activity but had no impact on the NPR.
      These results suggest that perihypoglossal GG premotoneurons near the obex
      mediate the NPR and those caudal to the obex are important mediators of
      respiratory-related GG activity but are not involved in the NPR.

PMID- 17185343
TI  - Regulation of the nuclear export of the transcription factor NFATc1 by protein
      kinases after slow fibre type electrical stimulation of adult mouse skeletal
      muscle fibres.
AB  - The transcription factor nuclear factor of activated T cells (NFAT)c1 has been
      shown to be involved in turning on slow skeletal muscle fibre gene expression.
      Previous studies from our laboratory have characterized the stimulation pattern
      dependent nuclear import and resting shuttling of NFATc1-green fluorescent
      protein (GFP) in flexor digitorum brevis (FDB) muscle fibres from adult mouse. In
      this study, we use viral expression of the transcription factor NFATc1-GFP fusion
      protein to investigate the mechanisms underlying the nuclear export of the NFATc1
      GFP that accumulated in the nuclei of cultured dissociated adult mouse FDB muscle
      fibres during slow-twitch fibre type electrical stimulation. In these studies, we
      found that inhibition of either glycogen synthase kinase 3beta (GSK3beta) or
      casein kinase 1 or 2 (CK1/2) markedly slowed the decay of nuclear NFATc1-GFP
      after cessation of muscle fibre electrical stimulation, whereas inhibition of
      casein kinase 1delta, p38 mitogen-activated protein kinase, c-Jun N-terminal
      kinase and protein kinase A had little effect. Simultaneous inhibition of
      GSK3beta and CK1/2 completely blocked the nuclear export of NFATc1-GFP after
      muscle activity. We also developed a simplified model of NFATc1
      phosphorylation/dephosphorylation and nuclear fluxes, and used this model to
      simulate the observed time courses of nuclear NFATc1-GFP with and without NFATc1
      kinase inhibition. Our results suggest that GSK3beta and CK1/2 are the major
      protein kinases that contribute to the removal of NFATc1 that accumulates in
      muscle fibre nuclei during muscle activity, and that GSK3beta and CK1/2 are
      responsible for phosphorylating NFATc1 in muscle nuclei in a complementary or
      synergistic fashion.

PMID- 17185344
TI  - Human cerebral autoregulation before, during and after spaceflight.
AB  - Exposure to microgravity alters the distribution of body fluids and the degree of
      distension of cranial blood vessels, and these changes in turn may provoke
      structural remodelling and altered cerebral autoregulation. Impaired cerebral
      autoregulation has been documented following weightlessness simulated by head
      down bed rest in humans, and is proposed as a mechanism responsible for
      postspaceflight orthostatic intolerance. In this study, we tested the hypothesis
      that spaceflight impairs cerebral autoregulation. We studied six astronauts
      approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on
      landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by
      beat changes of photoplethysmographic mean arterial pressure and transcranial
      Doppler middle cerebral artery blood flow velocity were measured during 5 min of
      spontaneous breathing, 30 mmHg lower body suction to simulate standing in space,
      and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral
      autoregulation was quantified by analysis of the transfer function between
      spontaneous changes of mean arterial pressure and cerebral artery blood flow
      velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency
      (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not
      change significantly from preflight values during or after spaceflight.
      Reductions of cerebral blood flow velocity during lower body suction were
      significant before spaceflight (P < 0.05, repeated measures ANOVA), but not
      during or after spaceflight. Absolute and percentage reductions of mean (+/-
      s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after
      than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(
      1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4%
      before, P < 0.05), consistent with improved rather than impaired cerebral blood
      flow regulation. Low-frequency gain decreased significantly (P < 0.05) by 26, 23
      and 27% after 1 and 2 weeks in space and on landing day, respectively, compared
      with preflight values, which is also consistent with improved autoregulation. We
      conclude that human cerebral autoregulation is preserved, and possibly even
      improved, by short-duration spaceflight.

PMID- 17185345
TI  - Metachronal coupling between spinal neuronal networks during locomotor activity
      in newborn rat.
AB  - In the present study, we investigate spinal cord neuronal network interactions in
      the neonatal rat during locomotion. The behavioural and physiological relevance
      of metachronally propagated locomotor activity were inferred from kinematic,
      anatomical and in vitro electrophysiological data. Kinematic analysis of freely
      behaving animals indicated that there is a rhythmic sequential change in trunk
      curvature during the step cycle. The motoneurons innervating back and tail
      muscles were identified along the spinal cord using retrograde labelling.
      Systematic multiple recordings from ventral roots were made to determine the
      precise intrinsic pattern of coordination in the isolated spinal cord. During
      locomotor-like activity, rhythmic ventral root motor bursts propagate caudo
      rostrally in the sacral and the thoracic spinal cord regions. Plotting the
      latency as a function of the cycle period revealed that the system adapts the
      intersegmental latency to the ongoing motor period in order to maintain a
      constant phase relationship along the spinal axis. The thoracic, lumbar and
      sacral regions were capable of generating right and left alternating motor bursts
      when isolated. Longitudinal sections of the spinal cord revealed that both the
      bilateral antiphase pattern observed for the sacral region with respect to the
      lumbar segment 2 as well as the intersegmental phase lag were due to cross-cord
      connections. Together, these results provide physiological evidence that the
      dynamic changes observed in trunk bending during locomotion are determined by the
      intrinsic organization of spinal cord networks and their longitudinal and
      transverse interactions. Similarities between this organization, and that of
      locomotor pattern generation in more primitive vertebrates, suggest that the
      circuits responsible for metachronal propagation of motor patterns during
      locomotion are highly conserved.

PMID- 17185346
TI  - Mechanism of Ca2+ increase in myoblasts derived from chicken embryos.
AB  - The mechanism of intracellular calcium ions (Ca(2+)) increase in chicken
      myoblasts was studied using histological, immunohistochemical, immunoblotting and
      Ca(2+) imaging techniques. Mononuclear myoblasts at embryonic day 12 (E12)
      contained myofibrils in the peripheral cytoplasm, and the sarcoplasmic reticulum
      was observed in the cytoplasm. Several Ca(2+)-related receptors, namely
      acetylcholine (ACh) receptors, dihydropyridine receptors (DHPRs) and ryanodine
      receptors (RyRs), were detected in the tissue as early as E12. Western blotting
      analyses detected one band corresponding to RyR subtype 3 (RyR3) at E12 and two
      bands corresponding to RyR1 and RyR3 after E13. Ca(2+) imaging of mononuclear
      myoblasts in vitro revealed an intense Ca(2+)-increase response to ACh
      stimulation, and this effect was abolished after EGTA addition to the culture
      medium. Nifedipine treatment also led to a lack of Ca(2+) increase in response to
      ACh stimulation, while ryanodine treatment led to a weak Ca(2+)-increase
      response. On the other hand, multinuclear myoblasts showed a Ca(2+)-increase
      response to ACh stimulation in the presence of not only EGTA but also nifedipine,
      although ryanodine treatment led to a lack of Ca(2+) increase. These results
      suggest that the mechanism of Ca(2+) increase in mononuclear myoblasts involves
      extracellular Ca(2+) entry through DHPRs, which is amplified by Ca(2+) release
      from the cytoplasmic Ca(2+) store, while multinuclear myoblasts mainly depend on
      Ca(2+) release from the cytoplasmic Ca(2+) store.

PMID- 17185347
TI  - Embedment-free section electron microscopy.
AB  - Because of potential hindrance of clear viewing in epoxy sections of biological
      entities having an electron density similar to and lower than that of epoxy
      resin, the author has stressed that the embedment-free section electron
      microscopy is necessary for re-examination and/or clarification of biological
      specimen structures, and that the embedment-free electron microscopy is reliably
      done by using water-soluble polyethylene glycol (PEG) as a transient embedding
      media and by critical point-drying of embedment-free sections after de-embedment
      of PEG by immersion of semithin sections into water. With the embedment-free
      electron microscopy, the author has presented five major findings: the appearance
      of microtrabecular lattices with different compactnesses in various cells and in
      intracellular domains of a given cell, the faithful reproduction of
      microtrabecula-like strand lattices in vitro with increasing compactnesses from
      artificial protein solutions at correspondingly increasing concentrations, the
      appearance of more compact lattices from gelated gelatin than from solated
      gelatin at a given concentration in vitro, the changeability in compactnesses of
      the microtrabecular lattices by hyper- or hypotonic shock treatments of cells,
      and the confined appearance of an intracellular protein in the centripetal
      demilune of centrifuged ganglion cells which is occupied with the microtrabecular
      lattices of a substantial compactness. From these findings, several conclusions
      are drawn: individual strands themselves of the microtrabeculae are meaningless,
      the appearance of microtrabeculae represents the presence of proteins at a
      certain concentration, and it is therefore likely that the aqueous cytoplasm is
      equivalent to the aqueous solution. In addition, it is possible that the
      appearance of two contiguous lattice domains exhibiting different compactnesses
      in a given cell may represent the occurrence of a contiguity of sol to gel states
      of cytoplasmic domains. It is thus proposed that the localization and movement of
      intracellular organelles are controlled not only by the cytoskeletons but also by
      the concentration and sol/gel states of intracellular proteins. In addition,
      several potential usefulness of the embedment-free electron microscopy has also
      been demonstrated.

PMID- 17185348
TI  - Physiological mechanisms dissociating pulmonary CO2 and O2 exchange dynamics
      during exercise in humans.
AB  - During moderate exercise (below the lactate threshold, (thetaL)), muscle CO(2)
      production ( Q(CO2)) kinetics are monoexponential, with a time constant (tau)
      similar to that of O(2) consumption. Following a delay incorporating the muscle
      lung vascular transit time, Q(CO2) is expressed at the lungs (V(CO2)) with an
      appreciably longer tau, reflecting the influence of intervening high-capacitance
      CO(2) stores. Above (thetaL), kinetics become complex, resulting from the
      conflation of the differing rates of HCO(3)(-) breakdown and degrees of
      compensatory hyperventilation with that of the underlying aerobic component.
      During incremental exercise, the increased rate of relative to pulmonary O(2)
      uptake (V(CO2)) can be used to quantify (thetaL) validly if aerobic and
      hyperventilatory sources can be ruled out, i.e. (thetaL) is then attributable to
      the decrease in muscle and blood [HCO(3)(-)]. In many cases, however, very rapid
      incrementation of work rate and/or prior depletion of CO(2) stores (by volitional
      or anticipatory hyperventilation) can yield a 'false positive' non-invasive
      estimation of (thetaL) ('pseudo-threshold') resulting from a slowing of the rate
      of wash-in of transient CO(2) stores.

PMID- 17185349
TI  - Oxygen exchange in muscle of young and old rats: muscle-vascular-pulmonary
      coupling.
AB  - Sustained performance of muscular exercise is contingent upon increasing muscle
      O(2) delivery (Qo2; the product of blood flow and arterial O(2) content, i.e. Q X
      Cao2) and utilization (Vo2m ) rapidly at exercise onset and sustaining necessary
      conductive and diffusive O(2) fluxes throughout exercise. A tight co-ordination
      of pulmonary, cardiovascular and muscle system responses is therefore required to
      prevent muscle microvascular O(2) pressures (P(mvO(2))) from falling to levels
      that impair blood-muscle O(2) exchange and/or impact metabolic control and reduce
      exercise tolerance. Microvascular O(2) pressures are determined by the balance
      between and Qo2 and Vo2m, and emerging evidence indicates that this balance is
      regulated differently across muscle fibre types and also in aged muscle.
      Moreover, disease states such as diabetes (type I and II) and chronic heart
      failure (CHF) also impact P(mvO(2)). This brief review primarily examines
      evidence obtained in animals that ageing: (1) redistributes exercising away from
      highly oxidative muscles and muscle fibres; (2) alters muscle capillary
      haemodynamics; and (3) reduces the O(2) pressure head within the microcirculation
      (P(mvO(2))) that serves to facilitate blood-muscle O(2) transfer. In many
      respects, these alterations found in healthy ageing animals bear a striking
      resemblance to those present in some chronic diseases (e.g. diabetes, CHF) and
      may help explain the compromised exercise tolerance present in aged individuals.
      Putative mechanistic insights are explored within the context of current
      knowledge and future investigative approaches.

PMID- 17185350
TI  - Eccentric cardiac hypertrophy was induced by long-term intermittent hypoxia in
      rats.
AB  - It is unclear whether cardiac hypertrophy and hypertrophy-related pathways will
      be induced by long-term intermittent hypoxia. Thirty-six Sprague-Dawley rats were
      randomly assigned into three groups: normoxia, and long-term intermittent hypoxia
      (12% O(2), 8 h per day) for 4 weeks (4WLTIH) or for 8 weeks (8WLTIH). Myocardial
      morphology, trophic factors and signalling pathways in the three groups were
      determined by heart weight index, histological analysis, Western blotting and
      reverse transcriptase-polymerase chain reaction from the excised left ventricle.
      The ratio of whole heart weight to body weight, the ratio of left ventricular
      weight to body weight, the gross vertical cross-section of the heart and
      myocardial morphological changes were increased in the 4WLTIH group and were
      further augmented in the 8WLTIH group. In the 4WLTIH group, tumour necrosis
      factor-alpha(TNFalpha), insulin-like growth factor (IGF)-II, phosphorylated p38
      mitogen-activated protein kinase (P38), signal transducers and activators of
      transcription (STAT)-1 and STAT-3 were significantly increased in the cardiac
      tissues. However, in the 8WLTIH group, in addition to the above factors,
      interleukin-6, mitogen-activated protein kinase (MEK)5 and extracellular signal
      regulated kinase (ERK)5 were significantly increased compared with the normoxia
      group. We conclude that cardiac hypertrophy associated with TNFalpha and IGF-II
      was induced by intermittent hypoxia. The longer duration of intermittent hypoxia
      further activated the eccentric hypertrophy-related pathway, as well as the
      interleukin 6-related MEK5-ERK5 and STAT-3 pathways, which could result in the
      development of cardiac dilatation and pathology.

PMID- 17185351
TI  - Origin and outcome of pregnancies affected by androgenetic/biparental chimerism.
AB  - BACKGROUND: Androgenetic diploid cells confined to the placenta have recently
      been reported in several cases of normally developed fetuses in association with
      placental mesenchymal dysplasia (PMD). METHODS AND RESULTS: We investigated two
      singleton, mildly growth-restricted, female pregnancies ascertained on the basis
      of PMD. One case had liver hemangiomas and both infants had multiple skin
      hemangiomas. Post-natal development was normal. Molecular marker analysis
      confirmed the diagnosis of androgenetic and normal mixed cell populations in the
      placenta. Both cases derived from a single maternal genome (M1) and two distinct
      paternal genomes (P1 and P2). In one case, the androgenetic cell population
      contained both paternal genomes (P1P2), with one shared in common with the
      biparental (M1P1) population. In the second case, the androgenetic lineage showed
      complete homozygosity (P2P2) for a paternal genome not common to the biparental
      cell population. CONCLUSION: These new PMD cases help to define the range of
      possible clinical presentations of androgenetic/biparental mosaicism or
      chimerism. Placentas with androgenetic/biparental chimeric cell populations may
      derive from a single tri-pronuclear (3PN) zygote in which one or more parental
      genomes are not equally apportioned to the daughter cells in the first cell
      division.

PMID- 17185352
TI  - Critical role of c-jun (NH2) terminal kinase in paracetamol- induced acute liver
      failure.
AB  - BACKGROUND: Acute hepatic failure secondary to paracetamol poisoning is
      associated with high mortality. C-jun (NH2) terminal kinase (JNK) is a member of
      the mitogen-activated protein kinase family and is a key intracellular signalling
      molecule involved in controlling the fate of cells. AIM: To examine the role of
      JNK in paracetamol-induced acute liver failure (ALF). METHODS: A previously
      developed mouse model of paracetamol poisoning was used to examine the role of
      JNK in paracetamol-induced ALF. RESULTS: Paracetamol-induced hepatic JNK
      activation both in human and murine paracetamol hepatotoxicity and in our murine
      model preceded the onset of hepatocyte death. JNK inhibition in vivo (using two
      JNK inhibitors with different mechanisms of action) markedly reduced mortality in
      murine paracetamol hepatotoxicity, with a significant reduction in hepatic
      necrosis and apoptosis. In addition, delayed administration of the JNK inhibitor
      was more effective than N-acetylcysteine after paracetamol poisoning in mice. JNK
      inhibition was not protective in acute carbon tetrachloride-mediated or anti-Fas
      antibody-mediated hepatic injury, suggesting specificity for the role of JNK in
      paracetamol hepatotoxicity. Furthermore, disruption of the JNK1 or JNK2 genes did
      not protect against paracetamol-induced hepatic damage. Pharmacological JNK
      inhibition had no effect on paracetamol metabolism, but markedly inhibited
      hepatic tumour necrosis foctor alpha (TNF alpha) production after paracetamol
      poisoning. CONCLUSIONS: These data demonstrated a central role for JNK in the
      pathogenesis of paracetamol-induced liver failure, thereby identifying JNK as an
      important therapeutic target in the treatment of paracetamol hepatotoxicity.

PMID- 17185353
TI  - Norepinephrine increases the pathogenic potential of Campylobacter jejuni.
AB  - BACKGROUND: Campylobacter jejuni can cause a spectrum of diseases in humans,
      ranging from enteritis and diarrhoea to severe inflammation, profuse bloody
      diarrhoea and chronic relapsing infection. Norepinephrine (NE) levels in the
      intestine increase under conditions of stress and trauma, and are thought to
      result in spill over of NE into the intestinal lumen. NE is known to stimulate
      the growth of a range of bacterial species, and to increase the pathogenicity of
      Escherichia coli. AIM: To determine the effects of NE on the pathogenic potential
      of C jejuni in a model system. METHODS: C jejuni was grown in iron-replete and
      iron-limited media in the presence and absence of 100 microM NE. Several
      virulence-associated characteristics, including motility and cell invasion, were
      measured. RESULTS: When C jejuni was grown in iron-limited media in the presence
      of NE, growth rate, motility and invasion of cultured epithelial cells were
      increased compared with cultures grown in the absence of NE. Bacteria exposed to
      NE during growth also caused greater subsequent disruption of cultured epithelial
      cell monolayers, inducing widespread breakdown of tight junctions. CONCLUSION:
      Exposure to NE causes an increase in the virulence-associated properties of
      Campylobacter. Stress and concomitant infection could therefore be contributory
      factors to the variable presentation of this disease.

PMID- 17185354
TI  - Retinoic acid-induced glandular differentiation of the oesophagus.
AB  - BACKGROUND: Retinoic acid (RA) is a powerful differentiation agent. Barrett's
      oesophagus occurs when duodeno-gastro-oesophageal reflux causes squamous
      epithelium (SE) tissue to become columnar epithelium tissue by an unknown
      mechanism. The bile acid lithocholic acid (LCA) competes for the retinoid X
      receptor retinoid binding site. Hence, RA pathways may be implicated in Barrett's
      oesophagus. METHODS: RA activity in tissues and cell lines treated with all-trans
      retinoic acid (ATRA) with or without LCA was assessed using a reporter.
      Expression of p21 was determined by real-time PCR in Barrett's oesophagus cell
      lines with or without LCA. SE and Barrett's oesophagus biopsy specimens were
      exposed to 100 muM of ATRA or 20 mM of a RA inhibitor, citral, in organ culture
      for >72 h. Characteristics of treated specimens, compared with untreated
      controls, were analysed by immunohistochemical analysis (cytokeratins (CKs),
      vimentin) and RT-PCR (CKs). Confocal microscopy assessed temporal changes in co
      localisation of CK8/18 and vimentin. Cell proliferation was assessed by bromo
      deoxyuridine incorporation and immunohistochemical analysis for Ki67 and p21.
      RESULTS: RA biosynthesis was increased in Barrett's oesophagus compared with SE
      (p<0.001). LCA and ATRA caused a synergistic increase in RA signalling as shown
      by increased p21 (p<0.01). Morphological and molecular analysis of SE exposed to
      ATRA showed columnar differentiation independent of proliferation. Metaplasia
      could be induced from the stromal compartment alone and vimentin expression co
      localised with CK8/18 at 24 h, which separated into CK8/18-positive glands and
      vimentin-positive stroma by 48 h. Citral-treated Barrett's oesophagus led to
      phenotypic and immunohistochemical characteristics of SE, which was independent
      of proliferation. CONCLUSION: RA activity is increased in Barrett's oesophagus
      and is induced by LCA. Under conditions of altered RA activity and an intact
      stroma, the oesophageal phenotype can be altered independent of proliferation.

PMID- 17185357
TI  - Estrogen selectively regulates chemokines in murine splenocytes.
AB  - Estrogen has striking effects on immunity and inflammatory autoimmune conditions.
      One potential mechanism of estrogen-induced regulation of immunity and
      inflammatory autoimmune conditions is by altering the secretion of chemokines by
      lymphocytes, an aspect not well addressed thus far. We found that estrogen has
      marked, but differential, effects on the secretion of chemokines from activated
      splenocytes. Estrogen treatment significantly increased the secretion of MCP-1,
      MCP-5, eotaxin, and stromal cell-derived factor 1beta from Con A-activated
      splenocytes when compared with placebo-treated controls, and it had no effects on
      the levels of RANTES, thymus and activation-regulated chemokine, and keratinocyte
      derived chemokine (KC) at 24 h. A kinetic analysis showed that chemokines tended
      to increase with stimulation time, but only MCP-1 and MCP-5 showed a biological
      trend of increasing in splenocytes from estrogen-treated mice, and KC was
      decreased significantly in estrogen-treated splenocytes at 18 h. Estrogen did not
      affect the protein levels of chemokine receptors CCR1 or CCR2 at 24 h. Estrogen
      induced alterations in the levels of MCP-1 and MCP-5 are mediated, in part, by
      IFN-gamma, as estrogen treatment of IFN-gamma null mice, unlike wild-type mice,
      did not up-regulate these chemokines. However, addition of recombinant IFN-gamma
      resulted in markedly increased secretion of MCP-1 and MCP-5 only in the cells
      derived from estrogen-treated mice. These studies provide novel data indicating
      that estrogen may promote inflammatory conditions by altering the levels of
      chemokines, providing evidence for an additional mechanism by which estrogens can
      regulate inflammation.

PMID- 17185356
TI  - A meta-analysis on the influence of inflammatory bowel disease on pregnancy.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) has a typical onset during the peak
      reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is
      important for the management of pregnancy to assist in its management. AIM: To
      provide a clear assessment of risk of adverse outcomes during pregnancy in women
      with IBD. DESIGN: The Medline literature was searched to identify studies
      reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis
      was used to compare outcomes between women with IBD and normal controls. PATIENTS
      AND SETTING: A total of 3907 patients with IBD (Crohn's disease 1952 (63%),
      ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies
      that satisfied the inclusion criteria. RESULTS: For women with IBD, there was a
      1.87-fold increase in incidence of prematurity (<37 weeks gestation; 95% CI 1.52
      to 2.31; p<0.001) compared with controls. The incidence of low birth weight
      (<2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p<0.001).
      Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI
      1.26 to 1.79; p<0.001), and the risk of congenital abnormalities was found to be
      2.37-fold increased (95% CI 1.47 to 3.82; p<0.001). CONCLUSION: The study has
      shown a higher incidence of adverse pregnancy outcomes in patients with IBD.
      Further studies are required to clarify which women are at higher risk, as this
      was not determined in the present study. This has an effect on the management of
      patients with IBD during pregnancy, who should be treated as a potentially high
      risk group.

PMID- 17185355
TI  - Ursodeoxycholic acid improves muscle contractility and inflammation in
      symptomatic gallbladders with cholesterol gallstones.
AB  - OBJECTIVE: To examine the mechanisms of action of ursodeoxycholic acid (UDCA) on
      gallbladder (GB) muscle cells in patients with symptomatic cholesterol gallstones
      (GSs) as it reduces the incidence of acute cholecystitis. DESIGN AND PATIENTS: A
      double-blind study was performed on 15 patients, 7 randomised to UDCA and 8 to
      placebo, treated for 4 weeks before cholecystectomy. Muscle contraction induced
      by cholecystokinin (CCK)-8, acetylcholine (ACh) and potassium chloride (KCl) was
      determined in enzymatically isolated GB muscle cells, and cholesterol levels were
      determined in plasma membranes. H(2)O(2), lipid peroxidation, platelet-activating
      factor (PAF)-like lipids, prostaglandin E(2) (PGE(2)) and catalase activity were
      determined as biochemical markers of oxidative stress and inflammation in muscle
      cells. RESULTS: UDCA significantly increased GB muscle cell contraction induced
      by all concentrations of CCK-8, ACh and KCl, and reduced the plasma membrane
      cholesterol (mean (SD) 0.32 (0.16) vs 0.72 (0.5) micromol/mg of protein) compared
      with placebo. In GB muscle cells, UDCA treatment significantly decreased the
      levels of H(2)O(2) (4.4 (1.9) vs 13.7 (5.3) micromol/mg of protein), lipid
      peroxidation (malondialdehyde levels 1.3 (0.4) vs 2.52 (0.7) nmol/100 mg of
      protein), PAF-like lipids (8.9 (4.9) vs 29.6 (7.1) pg/mg of protein) as well as
      the production of PGE(2) (142 (47) vs 365 (125) pg/mg of protein) and catalase
      activity (14.5 (9.4) vs 35.8 (12.7) units/mg of protein) when compared with
      placebo. CONCLUSION: These studies suggest that UDCA treatment improves GB muscle
      contractility by decreasing the cholesterol content in the plasma membrane of
      muscle cells, and the biochemical parameters of oxidative stress, thus explaining
      its possible therapeutic mechanisms in patients with symptoms of cholesterol GSs.

PMID- 17185358
TI  - Expression and function of the OX40/OX40L costimulatory pair during herpes
      stromal keratitis.
AB  - Herpes stromal keratitis (HSK) is an immunopathological disease regulated by Th1
      CD4 T cells, which require APC and costimulation within the infected cornea to
      mediate disease. Recent studies suggest the OX40:OX40 ligand (OX40L) interaction
      enhances effector cell cytokine secretion at inflammatory sites. OX40(+) cells
      were detected in HSV-1-infected mouse corneas as early as 3 days postinfection
      (dpi), prior to the onset of HSK, and their frequency increased through 15 dpi,
      when all mice exhibited severe HSK. OX40L(+) cells were first detected at 7 dpi,
      coincident with the initiation of HSK. It is interesting that the OX40L(+) cells
      did not coexpress MHC Class II or the dendritic cell (DC) marker CD11c. Our
      findings demonstrate rapid infiltration of activated (OX40(+)) CD4(+) T cells
      into HSV-1-infected corneas and expression of OX40L on MHC Class II-negative
      cells but surprisingly, not on MHC Class II(+) CD11c(+) DC, which are present in
      the infected corneas and required for HSK. Moreover, neither local nor systemic
      treatment of mice with a blocking antibody to OX40L or with a blocking fusion
      protein altered the course of HSK significantly, possibly as a result of a lack
      of OX40L expression on functional APC.

PMID- 17185359
TI  - Hemopexin domains as multifunctional liganding modules in matrix
      metalloproteinases and other proteins.
AB  - The heme-binding hemopexin consists of two, four-bladed propeller domains
      connected by a linker region. Hemopexin domains are found in different species on
      the phylogenetic tree and in the human species represented in hemopexin, matrix
      metalloproteinases (MMPs), vitronectin, and products of the proteoglycan 4 gene.
      Hemopexin and hemopexin domains of human proteins fulfill functions in activation
      of MMPs, inhibition of MMPs, dimerization, binding of substrates or ligands,
      cleavage of substrates, and endocytosis by low-density lipoprotein receptor
      related protein-1 (LRP-1; CD91) and LRP-2 (megalin, GP330). Insights into the
      structures and functions of hemopexin (domains) form the basis for positive or
      negative interference with the formation of molecular complexes and hence, might
      be exploited therapeutically in inflammation, cancer, and wound healing.

PMID- 17185360
TI  - Noncoding RNA synthesis and loss of Polycomb group repression accompanies the
      colinear activation of the human HOXA cluster.
AB  - The ratio of noncoding to protein coding DNA rises with the complexity of the
      organism, culminating in nearly 99% of nonprotein coding DNA in humans.
      Nevertheless, a large portion of these regions is transcribed, creating the
      alleged paradox that noncoding RNA (ncRNA) represents the largest output of the
      human genome. Such a complex scenario may include epigenetic mechanisms where
      ncRNAs would be involved in chromatin regulation. We have investigated the
      intergenic, noncoding transcriptomes of mammalian HOX clusters. We show that
      "opposite strand transcription" from the intergenic spacer regions in the human
      HOXA cluster correlates with the activity state of adjacent HOXA genes. This
      noncoding transcription is regulated by the retinoic acid morphogen and follows
      the colinear activation pattern of the cluster. Opening of the cluster at sites
      of activation of intergenic transcripts is accompanied by changes in histone
      modifications and a loss of interaction with Polycomb group (PcG) repressive
      complexes. We propose that noncoding transcription is of fundamental importance
      for the opening and maintenance of the active state of HOX clusters.

PMID- 17185362
TI  - Novel biosensor-based analytic device for the detection of anti-double-stranded
      DNA antibodies.
AB  - BACKGROUND: Patients with systemic lupus erythematosus (SLE) develop a wide
      variety of serologic manifestations, including double-stranded DNA autoantibodies
      (anti-dsDNA). The determination of the potentially pathogenic autoantibodies is
      diagnostically relevant. METHODS: We developed a novel surface plasmon resonance
      (SPR) biosensor chip for studies of dsDNA and anti-dsDNA binding. A synthetic
      oligonucleotide was coupled to biotinylated human transferrin, hybridized with
      the complementary antistrand, and ligated with a human recombinant dsDNA fragment
      233 bp in length. After surface immobilization of this antigenic construct,
      diluted sera from SLE patients and healthy donors were analyzed with the
      resulting SPR biosensor system. RESULTS: This SPR biosensor allowed specific
      detection of anti-dsDNA. In pilot experiments, sera from SLE patients were
      distinguished from control sera. We also confirmed the specificity of this
      biosensor by supplementing anti-dsDNA-positive sera with salmon sperm DNA, which
      blocked the surface binding of anti-dsDNA in a concentration-dependent manner.
      CONCLUSIONS: An SPR biosensor monitors interactions in real time under
      homogeneous conditions, providing information about binding kinetics and
      affinities. Its applicability critically depends on the design of the solid-state
      surface of the sensor chips. Covalently immobilizing dsDNA as the antigen to the
      surface in a flow-through cell assured maximal stability for multiple serum
      injections and regeneration cycles. This technique, which adds a new analytic
      quality to existing methods, may be beneficial in the diagnosis and clinical
      monitoring of SLE.

PMID- 17185361
TI  - Long-distance RNA-RNA interactions between terminal elements and the same subset
      of internal elements on the potato virus X genome mediate minus- and plus-strand
      RNA synthesis.
AB  - Potexvirus genomes contain conserved terminal elements that are complementary to
      multiple internal octanucleotide elements. Both local sequences and structures at
      the 5' terminus and long-distance interactions between this region and internal
      elements are important for accumulation of potato virus X (PVX) plus-strand RNA
      in vivo. In this study, the role of the conserved hexanucleotide motif within SL3
      of the 3' NTR and internal conserved octanucleotide elements in minus-strand RNA
      synthesis was analyzed using both a template-dependent, PVX RNA-dependent RNA
      polymerase (RdRp) extract and a protoplast replication system. Template analyses
      in vitro indicated that 3' terminal templates of 850 nucleotides (nt), but not
      200 nt, supported efficient, minus-strand RNA synthesis. Mutational analyses of
      the longer templates indicated that optimal transcription requires the
      hexanucleotide motif in SL3 within the 3' NTR and the complementary CP
      octanucleotide element 747 nt upstream. Additional experiments to disrupt
      interactions between one or more internal conserved elements and the 3'
      hexanucleotide element showed that long-distance interactions were necessary for
      minus-strand RNA synthesis both in vitro and in vivo. Additionally, multiple
      internal octanucleotide elements could serve as pairing partners with the
      hexanucleotide element in vivo. These cis-acting elements and interactions
      correlate in several ways to those previously observed for plus-strand RNA
      accumulation in vivo, suggesting that dynamic interactions between elements at
      both termini and the same subset of internal octanucleotide elements are required
      for both minus- and plus-strand RNA synthesis and potentially other aspects of
      PVX replication.

PMID- 17185363
TI  - Circulating concentrations of growth-differentiation factor 15 in apparently
      healthy elderly individuals and patients with chronic heart failure as assessed
      by a new immunoradiometric sandwich assay.
AB  - BACKGROUND: Growth-differentiation factor 15 (GDF15) is a member of the
      transforming growth factor beta (TGF-beta) cytokine superfamily. There has been
      increasing interest in using circulating GDF15 as a biomarker in patients, for
      example those with cardiovascular disease. METHODS: We developed an IRMA that
      uses a polyclonal, affinity chromatography-purified goat antihuman GDF15 IgG
      antibody, assessed the preanalytic characteristics of GDF15, and determined
      circulating GDF15 concentrations in 429 apparently healthy elderly individuals
      and 153 patients with chronic heart failure (CHF). RESULTS: The assay had a
      detection limit of 20 ng/L, an intraassay imprecision of < or =10.6%, and an
      interassay imprecision of < or =12.2%. Specificity was demonstrated with size
      exclusion chromatography, parallel measurements with polyclonal and monoclonal
      anti-GDF15 antibody, and lack of cross-reactivity with TGF-beta. The assay was
      not appreciably influenced by the anticoagulant matrix or unrelated biological
      substances. GDF15 was stable at room temperature for 48 h and resistant to 4
      freeze-thaw cycles. Apparently healthy, elderly individuals presented with a
      median GDF15 concentration of 762 ng/L (25th-75th percentiles, 600-959 ng/L).
      GDF15 concentrations were associated with age and with cystatin C and C-reactive
      protein concentrations. CHF patients had increased GDF15 concentrations that were
      closely related to disease severity. CONCLUSION: The IRMA can detect GDF15 in
      human serum and plasma with excellent sensitivity and specificity. The reference
      limits and confounding variables defined for apparently healthy elderly
      individuals and the favorable preanalytic characteristics of GDF15 are expected
      to facilitate future studies of GDF15 as a biomarker in various disease settings,
      including CHF.

PMID- 17185364
TI  - Asymmetrical dimethylarginine independently predicts total and cardiovascular
      mortality in individuals with angiographic coronary artery disease (the
      Ludwigshafen Risk and Cardiovascular Health study).
AB  - BACKGROUND: Asymmetrical dimethylarginine (ADMA) is increased in conditions
      associated with increased risk of atherosclerosis. We investigated the use of
      ADMA to predict total and cardiovascular mortality in patients scheduled for
      coronary angiography. METHODS: In 2543 persons with and 695 without coronary
      artery disease (CAD) identified by angiography we measured ADMA and recorded
      total and cardiovascular mortality during a median follow-up of 5.45 years.
      RESULTS: ADMA was correlated positively to age, female sex, diabetes mellitus,
      former and current smoking, and C-reactive protein and inversely to HDL
      cholesterol and triglycerides. ADMA was not associated with body mass index,
      hypertension, LDL cholesterol, or the presence or absence of angiographic CAD.
      Glomerular filtration rate and homocysteine were the strongest predictors of
      ADMA. At the 2nd, 3rd and 4th quartile of ADMA, hazard ratios for all-cause
      mortality adjusted for age, sex, and cardiovascular risk factors were 1.12 [95%
      confidence interval (CI) 0.83-1.52], 1.35 (95% CI 1.01-1.81), and 1.87 (95% CI
      1.43-2.44), respectively, compared with the 1st quartile. Hazard ratios for
      cardiovascular death were 1.13 (95% CI 0.78-1.63), 1.42 (95% CI 1.00-2.02), and
      1.81 (95% CI 1.31-2.51). ADMA in the highest quartile remained predictive of
      mortality after accounting for medication at baseline. The predictive value of
      ADMA was similar to that in the entire cohort in persons with CAD, stable or
      unstable, but was not statistically significant in persons without angiographic
      CAD. CONCLUSIONS: ADMA concentration predicts all-cause and cardiovascular
      mortality in individuals with CAD independently of established and emerging
      cardiovascular risk factors.

PMID- 17185365
TI  - Impact of adjustment for quality on results of metaanalyses of diagnostic
      accuracy.
AB  - BACKGROUND: We examined whether and to what extent different strategies of
      defining and incorporating quality of included studies affect the results of
      metaanalyses of diagnostic accuracy. METHODS: We evaluated the methodological
      quality of 487 diagnostic-accuracy studies in 30 systematic reviews with the
      QUADAS (Quality Assessment of Diagnostic-Accuracy Studies) checklist. We applied
      3 strategies that varied both in the definition of quality and in the statistical
      approach to incorporate the quality-assessment results into metaanalyses. We
      compared magnitudes of diagnostic odds ratios, widths of their confidence
      intervals, and changes in a hypothetical clinical decision between strategies.
      RESULTS: Following 2 definitions of quality, we concluded that only 70 or 72 of
      487 studies were of "high quality". This small number was partly due to poor
      reporting of quality items. None of the strategies for accounting for differences
      in quality led systematically to accuracy estimates that were less optimistic
      than ignoring quality in metaanalyses. Limiting the review to high-quality
      studies considerably reduced the number of studies in all reviews, with wider
      confidence intervals as a result. In 18 reviews, the quality adjustment would
      have resulted in a different decision about the usefulness of the test.
      CONCLUSIONS: Although reporting the results of quality assessment of individual
      studies is necessary in systematic reviews, reader wariness is warranted
      regarding claims that differences in methodological quality have been accounted
      for. Obstacles for adjusting for quality in metaanalyses are poor reporting of
      design features and patient characteristics and the relatively low number of
      studies in most diagnostic reviews.

PMID- 17185366
TI  - Human plasma ATP concentration.
AB  - BACKGROUND: Human plasma ATP concentration is reported in many studies as roughly
      1000 nmol/L. The present study tested the hypothesis that the measured plasma ATP
      concentration is lower if ATP release from formed blood elements is inhibited
      during blood sample processing. A second hypothesis was that pretreatment with
      aspirin to inhibit platelets would reduce the measured plasma concentration of
      ATP. METHODS: Blood was sampled from the antecubital vein in 20 healthy
      individuals 30 and 60 min after ingestion of aspirin (325 mg) or placebo.
      Aliquots of each blood sample were added to the usual EDTA/saline solution to
      inhibit ATP catabolism, or to a new stabilizing solution designed to both stop
      ATP catabolism and inhibit ATP release from blood elements. The stabilizing
      solution contained NaCl, EDTA, tricine buffer, KCl, nitrobenzylthioinosine,
      forskolin, and isobutylmethylxanthine. Plasma ATP was measured with the luciferin
      luciferase assay with standard additions in each sample to determine ATP content.
      Hemoglobin concentration was used as an index of sample hemolysis, and the plasma
      ATP concentration was corrected for the hemolysis component. RESULTS: Aspirin
      pretreatment had no effect on plasma ATP concentrations. However, use of the
      stabilizing solution resulted in mean (SD) ATP concentrations 8-fold lower than
      the use of EDTA alone [28 (16) vs 236 (201) nmol/L; P <0.001]. CONCLUSION: When
      precautions are taken to inhibit ATP release from blood elements during sample
      preparation, human venous plasma ATP concentration is much lower than previously
      reported.

PMID- 17185367
TI  - Transcriptional profiling of hematologic malignancies with a low-density DNA
      microarray.
AB  - BACKGROUND: High-density microarrays are powerful tools for expression analysis
      of thousands of genes simultaneously; however, experience with low-density
      microarrays in gene expression studies has been limited. METHODS: We developed an
      optimized procedure for gene expression analysis based on a microarray containing
      538 oligonucleotides and used this procedure to analyze neoplastic cell lines and
      whole-blood samples from healthy individuals and patients with different
      hematologic neoplasias. Hierarchical clustering and the Welch t-test with
      adjusted P values were used for data analysis. RESULTS: This procedure detects
      0.2 fmol of mRNA and generates a linear response of 2 orders of magnitude, with
      CV values of <20% for hybridization and label replicates. We found statistically
      significant differences between Jurkat and U937 cell lines, between blood samples
      from 15 healthy donors and 59 chronic lymphocytic leukemia (CLL) samples, and
      between 6 acute myeloid leukemia patients and 4 myelodysplastic syndrome
      patients. A classification system constructed from the expression data predicted
      healthy or CLL status from a whole-blood sample with a 97% success rate.
      CONCLUSION: Transcriptional profiling of whole-blood samples was carried out
      without any cellular or sample manipulation before RNA extraction. This gene
      expression analysis procedure uncovered statistically significant differences
      associated with different hematologic neoplasias and made possible the
      construction of a classification system that predicts the healthy or CLL status
      from a whole-blood sample.

PMID- 17185368
TI  - Comparison of free and total forms of serum human kallikrein 2 and prostate
      specific antigen for prediction of locally advanced and recurrent prostate
      cancer.
AB  - BACKGROUND: We evaluated the association of total and free forms of serum human
      kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of
      unfavorable prognosis. METHODS: We retrospectively measured total PSA (tPSA),
      free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men
      [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical
      prostatectomy for clinically localized prostate cancer. Associations between
      biomarker concentrations and extracapsular extension, seminal vesicle invasion,
      and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA <
      or =10 microg/L, the group most commonly seen in clinical practice in the US, was
      analyzed. RESULTS: thK2 was the strongest predictor of extracapsular extension
      and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719,
      respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were
      significant predictors of BCR. hK2 forms, but not PSA forms, remained highly
      significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA, and
      thK2 in a multivariable model improved prediction compared with any biomarker
      used individually (AUC, 0.711, 0.755, and 0.752 for this combination predicting
      extracapsular extension, seminal vesicle invasion, and BCR, respectively; P
      <0.001 for all). CONCLUSIONS: Increased concentrations of hK2 in the blood are
      significantly associated with unfavorable features of prostate cancer, and thK2
      is predictive of locally advanced and recurrent cancer in patients with PSA < or
      =10 microg/L. Independent of tPSA and fPSA, hK2 predicts unfavorable prognosis.

PMID- 17185369
TI  - Accuracy and biological variation of human serum paraoxonase 1 activity and
      polymorphism (Q192R) by kinetic enzyme assay.
AB  - BACKGROUND: Paraoxonase 1 (PON1) phenotype is a better predictor of
      atherosclerosis risk than are PON1 genetic polymorphisms alone. Larger studies
      are required to determine the role of PON1 and there is a need for standardized
      PON1 assays between laboratories. METHODS: We have adapted 5 enzyme kinetic
      assays for high-throughput automated analysis of PON1 activity. Using different
      substrates and reaction conditions, we measured PON1 activity and used activity
      ratios to identify the PON1 Q192R genetic polymorphisms and assessed the accuracy
      of the genotype assignments in 79 adult study participants by comparing them with
      genotypes determined by AlwI restriction enzyme digestion of a 176-bp PCR
      amplification product from genomic DNA. Imprecision was determined using pooled
      serum and purified enzyme preparations. Biological variability was estimated by
      analysis of serial samples from 17 individuals. Variability parameters were
      compared with total cholesterol as a point of reference to a recognized biomarker
      of coronary heart disease risk. RESULTS: Salt stimulation and inhibition ratios
      were 97.4% and 94.7% correct in assigning Q192R genotype, respectively.
      Analytical imprecision (CV) was 1.0%-3.0% for phenylacetate and paraoxon
      substrate assays and 3.0%-8.0% for the para-nitrophenylacetate substrate assays.
      Combination of the 2 ratios into a double ratio resulted in 100% correct genotype
      classification. CONCLUSION: The described methods for measurement of PON1
      activity and accurate genotype assignment are rapid and have potential to
      facilitate the efficient investigation of PON1 status in clinical and
      epidemiological studies.

PMID- 17185370
TI  - Lateral flow immunoassay using Europium (III) chelate microparticles and time
      resolved fluorescence for eosinophils and neutrophils in whole blood.
AB  - BACKGROUND: A simple point-of-care method for measuring leukocyte counts in a
      doctor's office or emergency room could be of great importance. We developed a
      protocol for measuring cell count by disrupting the cell membrane and analyzing
      specific proteins within the cells and used it to analyze proteins from
      eosinophils and neutrophils. METHODS: Lateral immunochromatographic (ICR) assays
      have been developed for eosinophil protein X (EPX) and human neutrophil lipocalin
      (HNL) as measures of the concentration of eosinophils and neutrophils. The
      correlation between the lateral ICR assays and cell counting of eosinophils and
      neutrophils was performed manually and with an automated cell counter. RIA assays
      measuring the same analytes were also compared with the results from cell
      counting and lateral ICR assays. RESULTS: The optimized assays showed analytical
      detection limits below the clinical ranges of 3.36 microg/L and 2.05 microg/L for
      EPX and HNL, respectively. The recovery was 114.8%-122.8% for EPX and 94.5%-96.9%
      for HNL. The imprecision was 3%-17% CV for EPX over the whole range and 5%-16% CV
      for HNL. The correlation coefficients between manually counted cells and lateral
      ICR assays were 0.9 and 0.83 for EPX and HNL, respectively. CONCLUSION: The
      numbers of eosinophils and neutrophils in small amounts of blood can be estimated
      in the point-of-care setting by means of fast lateral ICR assays of EPX and HNL.

PMID- 17185371
TI  - Cost consequences of implementing an electronic decision support system for
      ordering laboratory tests in primary care: evidence from a controlled prospective
      study in the Netherlands.
AB  - BACKGROUND: The economic consequences of interventions to promote rational,
      evidence-based use of laboratory tests by physicians are not yet fully
      understood. We evaluated the cost consequences of a computer-based, guideline
      driven decision-support system (CDSS) for ordering blood tests in primary care.
      METHODS: We installed the CDSS in 118 practices [159 general practitioners (GPs)]
      throughout The Netherlands and calculated the costs of the intervention in this
      group. During a period of 6 months before and 6 months after installation of the
      CDSS, the test-ordering behavior of 87 (109 GPs) of these 118 study practices was
      studied and the results were compared with those of a nonhistorical control group
      that did not receive the CDSS. In addition the costs of laboratory requests were
      calculated for both groups. RESULTS: Total intervention costs, comprising
      development costs and installation costs, amounted to 79,000 euro (670 euro per
      practice). Whereas the introduction of the CDSS did not affect the number of
      order forms submitted to the laboratories, it did reduce the number of blood
      tests per order form. As a result, the CDSS yielded mean savings on the costs of
      laboratory requests of 847 euro per practice per 6 months. CONCLUSIONS: This
      study demonstrates that providing electronic decision support for ordering blood
      tests in primary care represents an economically promising concept. Savings on
      laboratory costs are achievable and not offset by disproportionally high
      intervention costs.

PMID- 17185372
TI  - Gonadotropin-releasing hormone couples to 3',5'-cyclic adenosine-5'-monophosphate
      pathway through novel protein kinase Cdelta and -epsilon in LbetaT2 gonadotrope
      cells.
AB  - GnRH regulates the reproductive system by stimulating synthesis and release of
      gonadotropins. GnRH acts through a receptor coupled to multiple intracellular
      events including a rapid phosphoinositide turnover. Although the cAMP pathway is
      essential for gonadotrope function, the ability of GnRH to induce cAMP, as well
      as the coupling mechanisms involved, remain controversial. In this study, we
      established that GnRH increases intracellular cAMP levels in a concentration
      dependent manner in LbetaT2 gonadotrope cells (maximal increase, 2.5-fold;
      EC(50), 0.30 nm), and this was further evidenced by GnRH activation of a cAMP
      sensitive reporter gene. The GnRH effect was Ca(2+) independent, mimicked by the
      phorbol ester phorbol 12-myristate 13-acetate, and blocked by the protein kinase
      C (PKC) inhibitor bisindolylmaleimide, indicating that the GnRH effect was
      mediated by PKC. Pharmacological inhibition of conventional PKC isoforms with
      Go6976 did not prevent GnRH-induced cAMP production, whereas down-regulation of
      novel PKCdelta, -epsilon, and -theta by a long-term treatment with GnRH markedly
      reduced it. Expression of dominant-negative (DN) mutants of PKCdelta or -epsilon
      but not PKCtheta impaired GnRH activation of a cAMP-sensitive promoter,
      demonstrating that PKCdelta and -epsilon are the two endogenous isoforms
      mediating GnRH activation of the adenylyl cyclase (AC) pathway in LbetaT2 cells.
      Accordingly, we identified by RT-PCR and immunocytochemical analysis, two PKC
      sensitive AC isoforms, i.e. AC5 and AC7 as potential targets for GnRH. Lastly, we
      showed that only sustained stimulation of GnRH receptor significantly increased
      cAMP, suggesting that in vivo, the cAMP signaling pathway may be selectively
      recruited under intense GnRH release such as the preovulatory GnRH surge.

PMID- 17185373
TI  - Histone H3 phosphorylation in the rat pineal gland: adrenergic regulation and
      diurnal variation.
AB  - In this study, we investigated phosphorylation of Ser10 in histone H3 by
      norepinephrine (NE) in the rat pineal gland. In whole-animal studies, we
      demonstrated a marked increase in histone H3 phosphorylation in the rat pineal
      gland during the first half of the dark period. Exposure to light during this
      period caused a rapid decline in histone H3 phosphorylation with an estimated
      t1/2 of less than 15 min, indicating a high level of dephosphorylation activity.
      Corresponding studies in cultured pineal cells revealed that treatment with NE
      produced an increase in histone H3 phosphorylation that peaked between 2 and 3 h
      and declined rapidly by 4 h. The NE-induced histone H3 phosphorylation was
      blocked by cotreatment with propranolol or KT5720, a protein kinase A inhibitor,
      but not by prazosin or other kinase inhibitors. Moreover, only treatment with
      dibutyryl cAMP but not other kinase activators mimicked the effect of NE on
      histone H3 phosphorylation. The NE-stimulated H3 phosphorylation was markedly
      increased by cotreatment with a serine/threonine phosphatase inhibitor,
      tautomycin or okadaic acid, supporting a high level of ongoing histone H3
      dephosphorylation activity. Together, our results indicate that histone H3
      phosphorylation is a naturally occurring event at night in the rat pineal gland
      that is driven almost exclusively by a NE-->beta-adrenergic-->cAMP/protein kinase
      A signaling mechanism. This transient histone H3 phosphorylation probably
      reflects the nocturnal activation of multiple adrenergic-regulated genes in the
      rat pineal gland.

PMID- 17185374
TI  - KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is
      regulated by sex steroids and season.
AB  - The KiSS-1 gene encodes a family of peptides called kisspeptins, which are
      endogenous ligands for the G protein-coupled receptor GPR54. Kisspeptin function
      appears to be critical for GnRH secretion and the initiation of puberty. To test
      the hypothesis that steroid hormones regulate KiSS-1 mRNA expression in the ewe,
      we examined the brains of ovary-intact (luteal phase) and ovariectomized (OVX)
      ewes, as well as OVX ewes that received estradiol (E) or progesterone (P)
      replacement. KiSS-1 mRNA-expressing cells were predominantly located in the
      arcuate nucleus (ARC). Here, expression was increased after OVX but returned to
      the level of gonad-intact animals with E treatment. Treatment with P partially
      restored KiSS-1 expression toward gonad-intact levels. Double-label
      immunohistochemistry revealed that approximately 86% of kisspeptin-immunoreactive
      cells in the ARC are also P-receptor positive. Finally, we tested the hypothesis
      that KiSS-1 mRNA is lower during anestrus, due to a non-steroid-dependent
      seasonal effect. In OVX ewes, expression in the ARC was lower at the time of year
      corresponding to anestrus. We conclude that KiSS-1 expression in the ARC of the
      ewe brain is negatively regulated by chronic levels of E and P, suggesting that
      both steroids may exert negative feedback control on GnRH secretion through
      altered kisspeptin signaling. Furthermore, a seasonal alteration in KiSS-1
      expression in the ARC of OVX ewes strongly suggests that kisspeptin is
      fundamentally involved in the control of seasonal changes in reproductive
      function.

PMID- 17185375
TI  - Environmental control of kisspeptin: implications for seasonal reproduction.
AB  - The KiSS-1 gene encodes the peptide hormone kisspeptin, which acts as a principal
      positive regulator of the reproductive axis by directly stimulating GnRH neuron
      activity. To gain insight into a potential role for kisspeptin in integrating and
      relaying reproductively relevant stimuli to the GnRH system, we investigated
      changes in kisspeptin peptide expression associated with photoperiodic changes in
      reproductive state as well as pituitary and gonadal responses to peripheral
      kisspeptin injections. Seasonally breeding rodents undergo pronounced
      fluctuations in reproductive state in response to changing day lengths. In common
      with other rodent species, a majority of male Siberian hamsters (Phodopus
      sungorus) exhibit reproductive decline after exposure to short-day lengths. A
      subset of individuals fails to respond to day length information, however, and
      maintains their reproductive function. We exploited these individual differences
      to examine whether kisspeptin may act at the interface between external stimuli
      and the reproductive system. After extended exposure to short days, animals with
      a quiescent reproductive axis displayed a marked reduction in kisspeptin cell
      labeling in the anteroventral periventricular nucleus but robust kisspeptin
      immunoreactive staining in the arcuate nucleus. In contrast, animals with
      functional reproductive systems displayed high numbers of kisspeptin
      immunoreactive neurons in the anteroventral periventricular nucleus but a paucity
      of expression in the arcuate nucleus. Kisspeptin injections significantly
      elevated LH over preinjection levels regardless of photoperiod or reproductive
      state. Collectively, these findings suggest an important role for kisspeptin in
      coordinating and relaying environmentally relevant information to the
      reproductive axis as well as a role for this peptide in regulating seasonal
      changes in reproductive function.

PMID- 17185377
TI  - p38 mitogen-activated protein kinase regulates osteoblast differentiation through
      osterix.
AB  - p38 MAPK has been shown to regulate osteoblast differentiation. Inhibition of
      this kinase with inhibitors or dominant-negative mutant impedes osteoblast
      differentiation. Yet the molecular mechanism behind this regulation is not well
      understood. Here we provide evidence that the effect of p38 MAPK on osteoblast
      differentiation can be mediated by osterix (Osx), a transcription factor
      necessary and sufficient for osteoblast differentiation. Inhibition of p38 MAPK
      had minimal effects on differentiation of p53-/- osteoblasts, which had sustained
      Osx expression. Inhibition of p38 MAPK down-regulated the expression of Osx at
      both protein and mRNA levels, but not other transcription factors involved in
      osteoblast differentiation. More importantly, this inhibitory effect could be
      significantly relieved in osteoblasts overexpressing Osx. Further experiments
      support that Osx expression is mainly controlled by bone morphogenetic proteins
      existing in the culture medium, secreted by osteoblasts or provided by serum, and
      p38 MAPK plays a positive role in bone morphogenetic proteins-induced Osx
      expression. These findings identify a novel mechanism by which p38 MAPK regulates
      osteoblast differentiation.

PMID- 17185376
TI  - Role of hypothalamic adenosine 5'-monophosphate-activated protein kinase in the
      impaired counterregulatory response induced by repetitive neuroglucopenia.
AB  - Antecedent hypoglycemia blunts counterregulatory responses that normally restore
      glycemia, a phenomenon known as hypoglycemia-associated autonomic failure (HAAF).
      The mechanisms leading to impaired counterregulatory responses are largely
      unknown. Hypothalamic AMP-activated protein kinase (AMPK) acts as a glucose
      sensor. To determine whether failure to activate AMPK could be involved in the
      etiology of HAAF, we developed a model of HAAF using repetitive
      intracerebroventricular (icv) injection of 2-deoxy-D-glucose (2DG) resulting in
      transient neuroglucopenia in normal rats. Ten minutes after a single icv
      injection of 2DG, both alpha1- and alpha2-AMPK activities were increased 30-50%
      in arcuate and ventromedial/dorsomedial hypothalamus but not in other
      hypothalamic regions, hindbrain, or cortex. Increased AMPK activity persisted in
      arcuate hypothalamus at 60 min after 2DG injection when serum glucagon and
      corticosterone levels were increased 2.5- to 3.4-fold. When 2DG was injected icv
      daily for 4 d, hypothalamic alpha1- and alpha2-AMPK responses were markedly
      blunted in arcuate hypothalamus, and alpha1-AMPK was also blunted in mediobasal
      hypothalamus 10 min after 2DG on d 4. Both AMPK isoforms were activated normally
      in arcuate hypothalamus at 60 min. Counterregulatory hormone responses were
      impaired by recurrent neuroglucopenia and were partially restored by icv
      injection of 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside, an AMPK
      activator, before 2DG. Glycogen content increased 2-fold in hypothalamus after
      recurrent neuroglucopenia, suggesting that glycogen supercompensation could be
      involved in down-regulating the AMPK glucose-sensing pathway in HAAF. Thus,
      activation of hypothalamic AMPK may be important for the full counterregulatory
      hormone response to neuroglucopenia. Furthermore, impaired or delayed AMPK
      activation in specific hypothalamic regions may play a critical role in the
      etiology of HAAF.

PMID- 17185378
TI  - Par-4-dependent apoptosis by the dietary compound withaferin A in prostate cancer
      cells.
AB  - Deletion or mutation of the androgen receptor (AR) renders prostate tumors
      refractory to apoptosis by androgen ablation, the mainstay of prostate cancer
      therapy. To identify novel therapeutics that can induce apoptosis regardless of
      the AR status of prostate cancer cells, we screened dietary herbal compounds
      using a reporter assay for the prostate apoptosis response-4 (Par-4) gene, which
      induces p53- and PTEN-independent and cancer-selective apoptosis. One of the
      compounds, withaferin A (WA), a major constituent of the dietary compound
      Withania somnifera, induced Par-4-dependent apoptosis in androgen-refractory
      prostate cancer cells and regression of PC-3 xenografts in nude mice.
      Interestingly, restoration of wild-type AR in PC-3 (AR negative) cells abrogated
      both Par-4 induction and apoptosis by WA. Individually, WA and anti-androgens
      induced neither Par-4 nor apoptosis in androgen-responsive prostate cancer cells,
      yet in combination, WA and anti-androgen synergistically induced Par-4 and
      apoptosis in androgen-responsive prostate cancer cells. Thus, when judiciously
      combined with anti-androgens, WA inhibits survival of both androgen-responsive
      and androgen-refractory prostate cancer cells by a Par-4-dependent mechanism. As
      Par-4 up-regulation induces apoptosis in most tumor cells, our findings can be
      extended to high-throughput screens to identify synergistic combinations for both
      therapy-sensitive and therapy-resistant cancers.

PMID- 17185379
TI  - Cancer progression in the transgenic adenocarcinoma of mouse prostate mouse is
      related to energy balance, body mass, and body composition, but not food intake.
AB  - Calorie restriction can inhibit or delay carcinogenesis, reportedly due to a
      reduction in calorie intake rather than by concurrent changes in body mass and/or
      composition. Our objective was to test the hypothesis that body mass and/or
      composition have an important effect, independent of energy intake, on the
      benefits or hazards associated with calorie restriction or overeating,
      respectively. In the first experiment, transgenic mice that spontaneously develop
      prostate cancer [transgenic adenocarcinoma of mouse prostate (TRAMP)] were housed
      at 27 degrees C or 22 degrees C and pair fed the same diet for 21 weeks (95% of
      ad libitum intake at 27 degrees C). In the second experiment, TRAMP mice were
      housed at 27 degrees C or 22 degrees C and fed the same diet ad libitum for 21
      weeks. Despite a similar calorie intake, pair-fed mice at 27 degrees C (PF27)
      were heavier (28.3 +/- 3.3 versus 17.6 +/- 1.6 g at 21 weeks; P < 0.001; mean +/-
      SD) and had greater fat (6.4 +/- 2.1 versus 1.9 +/- 0.3 g; P < 0.001) and lean
      mass (P < 0.001) than pair-fed mice at 22 degrees C. Furthermore, PF27 mice had
      greater levels of serum leptin (P < 0.001), lower levels of adiponectin (P <
      0.05), and a greater frequency of prostatic adenocarcinoma (P < 0.05). In
      contrast, ad libitum-fed mice housed at 22 degrees C consumed approximately 30%
      more calories than ad libitum-fed mice at 27 degrees C, but there was no
      difference between groups in body composition or cancer progression. These
      results imply that the ability of calorie restriction to inhibit or delay cancer
      incidence and progression is mediated in part by changes in energy balance, body
      mass, and/or body composition rather than calorie intake per se, suggesting that
      excess calorie retention, rather than consumption, confers cancer risk.

PMID- 17185380
TI  - Molecular interactions underlying the unusually high adenosine affinity of a
      novel Trypanosoma brucei nucleoside transporter.
AB  - Trypanosoma brucei encodes a relatively high number of genes of the equilibrative
      nucleoside transporter (ENT) family. We report here the cloning and in-depth
      characterization of one T. brucei brucei ENT member, TbNT9/AT-D. This transporter
      was expressed in Saccharomyces cerevisiae and displayed a uniquely high affinity
      for adenosine (Km = 0.068 +/- 0.013 microM), as well as broader selectivity for
      other purine nucleosides in the low micromolar range, but was not inhibited by
      nucleobases or pyrimidines. This selectivity profile is consistent with the P1
      transport activity observed previously in procyclic and long-slender bloodstream
      T. brucei, apart from the 40-fold higher affinity for adenosine than for inosine.
      We found that, like the previously investigated P1 activity of long/slender
      bloodstream trypanosomes, the 3'-hydroxy, 5'-hydroxy, N3, and N7 functional
      groups contribute to transporter binding. In addition, we show that the 6
      position amine group of adenosine, but not the inosine 6-keto group, makes a
      major contribution to binding (DeltaG0 = 12 kJ/mol), explaining the different Km
      values of the purine nucleosides. We further found that P1 activity in procyclic
      and long-slender trypanosomes is pharmacologically distinct, and we identified
      the main gene encoding this activity in procyclic cells as NT10/AT-B. The
      presence of multiple P1-type nucleoside transport activities in T. brucei brucei
      facilitates the development of nucleoside-based treatments for African
      trypanosomiasis and would delay the onset of uptake-related drug resistance to
      such therapy. We show that both TbNT9/AT-D and NT10/AT-B transport a range of
      potentially therapeutic nucleoside analogs.

PMID- 17185382
TI  - Comments on "calpain mediates the dioxin-induced activation and down-regulation
      of the aryl hydrocarbon receptor".

PMID- 17185385
TI  - Two sites in the MAPT region confer genetic risk for Guam ALS/PDC and dementia.
AB  - Unusual forms of amyotrophic lateral sclerosis (ALS-G), Parkinsonism dementia
      complex (PDC-G) and Guam dementia (GD) are found in Chamorros, the indigenous
      people of Guam. Neurofibrillary tangles composed of hyperphosphorylated tau are a
      neuropathologic feature of these closely related disorders. To determine if
      variation in the gene that encodes microtubule-associated protein tau gene (MAPT)
      contributes to risk for these disorders, we genotyped nine single nucleotide
      polymorphism (SNP) sites and one insertion/deletion in the 5' end of MAPT in 54
      ALS-G, 135 PDC-G, 153 GD and 258 control subjects, all of whom are Chamorros.
      Variation at three SNPs (sites 2, 6 and 9) influenced risk for ALS-G, PDC-G and
      GD. SNP2 acts through a dominant mechanism and is independent of the risk
      conferred by SNPs 6 and 9, the latter two acting by a recessive mechanism.
      Persons with the high-risk SNP6 and SNP9 AC/AC diplotype had an increased risk of
      3-fold [95% confidence interval (CI)=1.10-8.25] for GD, 4-fold (95% CI=1.40
      11.64) for PDC-G and 6-fold (95% CI=1.44-32.14) for ALS-G, compared to persons
      with other diplotypes after adjusting for SNP2. Carriers of the SNP2 G allele had
      an increased risk of 1.6-fold (95% CI=1.00-2.62) for GD, 2-fold (95% CI=1.28
      3.66) for PDC-G, and 1.5-fold (95% CI=0.74-3.00) for ALS-G, compared to non
      carriers after adjusting for SNPs 6 and 9. Others have shown that SNP6 is also
      associated with risk for progressive supranuclear palsy. These two independent
      cis-acting sites presumably influence risk for Guam neuro-degenerative disorders
      by regulating MAPT expression.

PMID- 17185386
TI  - Families with the risk allele of DISC1 reveal a link between schizophrenia and
      another component of the same molecular pathway, NDE1.
AB  - We have previously reported a robust association between an allelic haplotype of
      'Disrupted in Schizophrenia 1' (DISC1) and schizophrenia in a nationwide
      collection of Finnish schizophrenia families. This specific DISC1 allele was
      later identified to associate with visual working memory, selectively in males.
      DISC1 association to schizophrenia has since been replicated in multiple
      independent study samples from different populations. In this study, we
      conditioned our sample of Finnish families for the presence of the Finnish
      tentative risk allele for DISC1 and re-analyzed our genome-wide scan data of 443
      markers on the basis of this stratification. Two additional loci displayed an
      evidence of linkage (LOD > 3) and included a locus on 16p13, proximal to the gene
      encoding NDE1, which has been shown to biologically interact with DISC1. Although
      none of the observed linkages remained significant after multiple test correction
      through simulation, further analysis of NDE1 revealed an association between a
      tag-haplotype and schizophrenia (P = 0.00046) specific to females, which proved
      to be significant (P = 0.011) after multiple test correction. Our finding would
      support the concept that initial gene findings in multifactorial diseases will
      assist in the identification of other components of complex genetic etiology.
      Notably, this and other converging lines of evidence underline the importance of
      DISC1-related functional pathways in the etiology of schizophrenia.

PMID- 17185387
TI  - Nuclear import and export signals are essential for proper cellular trafficking
      and function of ZIC3.
AB  - Missense, frameshift and nonsense mutations in the zinc finger transcription
      factor ZIC3 cause heterotaxy as well as isolated congenital heart disease.
      Previously, we developed transactivation and subcellular localization assays to
      test the function of ZIC3 point mutations. Aberrant cytoplasmic localization
      suggested that the pathogenesis of ZIC3 mutations results, at least in part, from
      failure of appropriate cellular trafficking. To further investigate this
      hypothesis, the nucleocytoplasmic shuttling properties of ZIC3 have been
      examined. Subcellular localization assays designed to span the entire open
      reading frame of wild-type and mutant ZIC3 proteins identified the presence of
      nucleocytoplasmic transport signals. ZIC3 domain mapping indicates that a
      relatively large region containing the zinc finger binding sites and a known GLI
      interacting domain is required for transport to the nucleus. Site-directed
      mutagenesis of critical residues within two putative nuclear localization signals
      (NLSs) leads to loss of nuclear localization. No further decrease was observed
      when both NLS sites were mutated, suggesting that mutation of either NLS site is
      sufficient for loss of importin-mediated nuclear localization. Additionally, we
      identify a cryptic CRM-1-dependent nuclear export signal (NES) within ZIC3, and
      identify a mutation within this region in a patient with heterotaxy. These
      results provide the first evidence that control of cellular trafficking of ZIC3
      is critical for function and suggest a possible mechanism for transcriptional
      control during left-right patterning. Identification of mutations in mapped NLS
      or NES domains in heterotaxy patients demonstrates the functional importance of
      these domains in cardiac morphogenesis and allows for integration of structural
      analysis with developmental function.

PMID- 17185389
TI  - The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required
      for primary cilium formation.
AB  - Meckel-Gruber syndrome (MKS) is an autosomal recessive lethal malformation
      syndrome characterized by renal cystic dysplasia, central nervous system
      malformations (typically, posterior occipital encephalocele), and hepatic
      developmental defects. Two MKS genes, MKS1 and MKS3, have been identified
      recently. The present study describes the cellular, sub-cellular and functional
      characterization of the novel proteins, MKS1 and meckelin, encoded by these
      genes. In situ hybridization studies for MKS3 in early human embryos showed
      transcript localizations in agreement with the tissue phenotype of MKS patients.
      Both MKS proteins predominantly localized to epithelial cells, including proximal
      renal tubules and biliary epithelial cells. MKS1 localized to basal bodies, while
      meckelin localized both to the primary cilium and to the plasma membrane in
      ciliated cell-lines and primary cells. Meckelin protein with the Q376P missense
      mutation was unable to localize at the cell membrane. siRNA-mediated reduction of
      Mks1 and Mks3 expression in a ciliated epithelial cell-line blocked centriole
      migration to the apical membrane and consequent formation of the primary cilium.
      Co-immunoprecipitation experiments show that wild-type meckelin and MKS1 interact
      and, in three-dimensional tissue culture assays, epithelial branching
      morphogenesis was severely impaired. These results suggest that MKS proteins
      mediate a fundamental developmental stage of ciliary formation and epithelial
      morphogenesis.

PMID- 17185388
TI  - Multiple ADH genes modulate risk for drug dependence in both African- and
      European-Americans.
AB  - Drug dependence (DD) is commonly co-morbid with alcohol dependence (AD). Many
      studies have also shown common genetic risk factors for these disorders. We
      previously reported associations of AD with seven alcohol dehydrogenase (ADH)
      genes. The present study examines the relationship between these genes and DD. We
      genotyped 16 markers within the ADH gene cluster and 38 unlinked ancestry
      informative markers in a case-control sample of 718 individuals. All markers were
      consistent with Hardy-Weinberg equilibrium in controls, but some markers showed
      Hardy-Weinberg disequilibrium in cases (minimal P = 0.002). Genotypes of many
      markers were associated with DD, both before and after controlling for admixture
      effects (minimal P < 1.0 x 10(-6)). Diplotype trend regression analysis showed
      that ADH5 and ADH6 genotypes, and diplotypes at ADH1A, ADH1B, ADH1C and ADH7
      (minimal P = 0.002), were associated with DD in European-Americans and/or African
      Americans. This first report of an allelic association of these loci with DD
      provides new insight into the mechanism of genetic risk for DD. These findings,
      obtained using a series of powerful and reliable analytic methods, may also help
      to explain the high rate of co-morbidity between AD and DD.

PMID- 17185390
TI  - Age-dependent accumulation of mtDNA mutations in murine hematopoietic stem cells
      is modulated by the nuclear genetic background.
AB  - Alterations in mitochondrial DNA (mtDNA) and consequent loss of mitochondrial
      function underlie the mitochondrial theory of aging. In this study, we
      systematically analyzed the mtDNA control region somatic mutation pattern in 2864
      single hematopoietic stem cells (HSCs) and progenitors, isolated by flow
      cytometry sorting on Lin(-)Kit(+)CD34(-) parameters from young and old C57BL/6
      (B6) and BALB/cBy (BALB) mice, to test the hypothesis that the accumulated mtDNA
      mutations in HSCs were strain-correlated and associated with HSC functional
      senescence during aging. An increased level of mtDNA mutations in single HSCs was
      observed in old B6 when compared with young B6 mice (P=0.003); in contrast, no
      significant age-dependent accumulation of mutations was observed in BALB mice
      (old versus young, P=0.202) and the level of mutations in both young and old BALB
      mice was close to that of old B6 mice (P>0.280). Cellular reactive oxygen species
      (ROS) in mouse HSCs could not be correlated with the level of mtDNA mutations in
      these cells, although B6 mice had a higher proportion of ROS(-) cells when
      compared with the BALB mice. Propagation assays of single HSCs showed B6 cells
      form larger colonies compared with cells from BALB mice, irrespective of age and
      mtDNA mutation load. We infer from our data that age-related mtDNA somatic
      mutation accumulation in mouse HSCs is influenced by the nuclear genetic
      background and that these mutations may not obviously correlate to either
      cellular ROS content or HSC senescence.

PMID- 17185391
TI  - Functional genomics of the beta-cell: short-chain 3-hydroxyacyl-coenzyme A
      dehydrogenase regulates insulin secretion independent of K+ currents.
AB  - Recent advances in functional genomics afford the opportunity to interrogate the
      expression profiles of thousands of genes simultaneously and examine the function
      of these genes in a high-throughput manner. In this study, we describe a rational
      and efficient approach to identifying novel regulators of insulin secretion by
      the pancreatic beta-cell. Computational analysis of expression profiles of
      several mouse and cellular models of impaired insulin secretion identified 373
      candidate genes involved in regulation of insulin secretion. Using RNA
      interference, we assessed the requirements of 10 of these candidates and
      identified four genes (40%) as being essential for normal insulin secretion.
      Among the genes identified was Hadhsc, which encodes short-chain 3-hydroxyacyl
      coenzyme A dehydrogenase (SCHAD), an enzyme of mitochondrial beta-oxidation of
      fatty acids whose mutation results in congenital hyperinsulinism. RNA
      interference-mediated gene suppression of Hadhsc in insulinoma cells and primary
      rodent islets revealed enhanced basal but normal glucose-stimulated insulin
      secretion. This increase in basal insulin secretion was not attenuated by the
      opening of the KATP channel with diazoxide, suggesting that SCHAD regulates
      insulin secretion through a KATP channel-independent mechanism. Our results
      suggest a molecular explanation for the hyperinsulinemia hypoglycemic seen in
      patients with SCHAD deficiency.

PMID- 17185392
TI  - The role of Xenopus membrane progesterone receptor beta in mediating the effect
      of progesterone on oocyte maturation.
AB  - Rapid, nongenomic membranal effects of progesterone were demonstrated in
      amphibian oocytes more than 30 y ago. Recently, a distinct family of membrane
      progestin receptors (mPRs) has been cloned in fish and other vertebrate species.
      In this study we explore the role of mPR in promoting oocyte maturation in
      Xenopus laevis. RT-PCR analysis indicates that Xenopus oocytes contain
      transcripts for the mPRbeta ortholog, similar to what has been reported in
      zebrafish oocytes, and Western blotting shows that the protein is expressed on
      the oocyte plasma membrane. Microinjection of mPRbeta-specific antibodies into
      oocytes resulted in a dramatic inhibition of progesterone-dependent oocyte
      maturation, whereas microinjection of mRNA encoding Myc-Xenopus mPR (XmPR)beta
      resulted in an accelerated rate of progesterone-induced oocyte maturation,
      concomitant with membranal localization of the protein. Binding studies in
      mammalian cells expressing XmPRbeta confirmed specific binding of progesterone by
      the expressed protein. These results suggest that XmPRbeta is a physiological
      progesterone receptor involved in initiating the resumption of meiosis during
      maturation of Xenopus oocytes.

PMID- 17185393
TI  - Identification of regions within the F domain of the human estrogen receptor
      alpha that are important for modulating transactivation and protein-protein
      interactions.
AB  - The estrogen receptor (ER)alpha is a biologically and clinically important ligand
      modulated transcription factor. The F domain of the ERalpha modulates its
      functions in a ligand-, promoter-, and cell-specific manner. To identify the
      region(s) responsible for these functions, we characterized the effects of serial
      truncations within the F domain. We found that truncating the last 16 residues of
      the F domain altered the activity of the human ERalpha (hERalpha) on an estrogen
      response element-driven promoter in response to estradiol or 4-hydroxytamoxifen
      (4-OHT), its sensitivity to overexpression of the coactivator steroid receptor
      coactivator-1 in mammalian cells, and its interaction with a receptor-interacting
      domain of the coactivator steroid receptor coactivator-1 or engineered proteins
      ("monobodies") that specifically bind to ERalpha/ligand complexes in a yeast two
      hybrid system. Most importantly, the ability of the ER to induce pS2 was reduced
      in MDA-MB-231 cells stably expressing this truncated ER vs. the wild-type ER. The
      region includes a distinctive segment (residues 579-584; LQKYYIT) having a high
      content of bulky and/or hydrophobic amino acids that was previously predicted to
      adopt a beta-strand-like structure. As previously reported, removal of the entire
      F domain was necessary to eliminate the agonist activity of 4-OHT. In addition,
      mutation of the vicinal glycine residues between the ligand-binding domain and F
      domains specifically reduced the 4-OHT-dependent interactions of the hERalpha
      ligand-binding domain and F domains with monobodies. These results show that
      regions within the F domain of the hERalpha selectively modulate its activity and
      its interactions with other proteins.

PMID- 17185394
TI  - Ubiquitination and proteasome-mediated degradation of BRCA1 and BARD1 during
      steroidogenesis in human ovarian granulosa cells.
AB  - Germ-line mutations in BRCA1 predispose women to early-onset, familial breast and
      ovarian cancers. However, BRCA1 expression is not restricted to breast and
      ovarian epithelial cells. For example, ovarian BRCA1 expression is enriched in
      ovarian granulosa cells, which are responsible for ovarian estrogen production in
      premenopausal women. Furthermore, recent tissue culture and animal studies
      suggest a functional role of BRCA1 in ovarian granulosa cells. Although levels of
      BRCA1 are known to fluctuate significantly during folliculogenesis and
      steroidogenesis, the mechanism by which BRCA1 expression is regulated in
      granulosa cells remains to be elucidated. Here we show that the ubiquitin
      proteasome degradation pathway plays a significant role in the coordinated
      protein stability of BRCA1 and its partner BARD1 in ovarian granulosa cells. Our
      work identifies the amino-terminal RING domain-containing region of BRCA1 as the
      degron sequence that is both necessary and sufficient for polyubiquitination and
      proteasome-mediated protein degradation. Interestingly, mutations in the RING
      domain that abolish the ubiquitin E3 ligase activity of BRCA1 do not affect its
      own ubiquitination or degradation in ovarian granulosa cells. The proteasome
      mediated degradation of BRCA1 and BARD1 also occurs during the cAMP-dependent
      steroidogenic process. Thus, the dynamic changes of BRCA1/BARD1 protein stability
      in ovarian granulosa cells provide an excellent paradigm for investigating the
      regulation of this protein complex under physiological conditions.

PMID- 17185397
TI  - Effects of distraction on pain, fear, and distress during venous port access and
      venipuncture in children and adolescents with cancer.
AB  - This study evaluates the effect of self-selected distracters (ie, bubbles, I Spy:
      Super Challenger book, music table, virtual reality glasses, or handheld video
      games) on pain, fear, and distress in 50 children and adolescents with cancer,
      ages 5 to 18, with port access or venipuncture. Using an intervention-comparison
      group design, participants were randomized to the comparison group (n = 28) to
      receive standard care or intervention group (n = 22) to receive distraction plus
      standard care. All participants rated their pain and fear, parents rated
      participant fear, and the nurse rated participant fear and distress at 3 points
      in time: before, during, and after port access or venipuncture. Results show that
      self-reported pain and fear were significantly correlated (P = .01) within
      treatment groups but not significantly different between groups. Intervention
      participants demonstrated significantly less fear (P <.001) and distress (P =
      .03) as rated by the nurse and approached significantly less fear (P = .07) as
      rated by the parent. All intervention parents said the needlestick was better
      because of the distracter. The authors conclude that distraction has the
      potential to reduce fear and distress during port access and venipuncture.

PMID- 17185395
TI  - Modulation of glucocorticoid receptor phosphorylation and transcriptional
      activity by a C-terminal-associated protein phosphatase.
AB  - The glucocorticoid receptor (GR) is phosphorylated at three major sites on its N
      terminus (S203, S211, and S226), and phosphorylation modulates GR-regulatory
      functions in vivo. We examined the phosphorylation site interdependence, the
      contribution of the receptor C-terminal ligand-binding domain, and the
      participation of protein phosphatases in GR N-terminal phosphorylation and gene
      expression. We found that GR phosphorylation at S203 was greater when S226 was
      not phosphorylated and vice versa, indicative of intersite dependency. We also
      observed that a GR derivative lacking the ligand-binding domain, which no longer
      binds the heat shock protein 90 (Hsp90) complex, exhibits increased GR
      phosphorylation at all three sites as compared with the full-length receptor. A
      GR mutation (F602S) that produces a receptor less dependent on Hsp90 for function
      as well as treatment with the Hsp90 inhibitor geldanamycin also increased basal
      GR phosphorylation at a subset of sites. Pharmacological inhibition of
      serine/threonine protein phosphatases increased GR basal phosphorylation.
      Likewise, a reduction in protein phosphatase 5 protein levels enhanced GR
      phosphorylation at a subset of sites and selectively reduced the induction of
      endogenous GR target genes. Together, our findings suggest that GR undergoes a
      phosphorylation/dephosphorylation cycle that maintains steady-state receptor
      phosphorylation at a low basal level in the absence of ligand. Our findings also
      suggest that the ligand-dependent increase in GR phosphorylation results, in
      part, from the dissociation of a ligand-binding domain-linked protein
      phosphatase(s), and that changes in the intracellular concentration of protein
      phosphatase 5 differentially affect GR target gene expression.

PMID- 17185399
TI  - Propofol use in pediatric patients with severe cancer pain at the end of life.
AB  - This article describes the use and effectiveness of adjuvant propofol for pain
      control for pediatric oncology patients at the end of life. All patients
      experienced severe pain and agitation, not well controlled by continuous infusion
      opioids and benzodiazepines. Upon starting propofol, most patients had a
      temporary stabilization in the dose of opioids with subjective improvement in
      pain control, increased alertness, and improved ability to interact. Propofol
      infusions were continued until death in most patients. Two patients received
      propofol infusions at home. Subsequent increases in opioids in 6 patients and
      propofol in all patients were required for optimal pain control. Adverse effects
      included agitation in 5 patients and hallucinations in 2, which were controllable
      with benzodiazepines. One patient developed severe tetany, requiring propofol
      interruption; propofol was successfully restarted at a lower dose with an
      adjuvant benzodiazepine. The authors conclude that propofol is a useful and
      tolerable adjuvant agent for pain management in pediatric oncology patients at
      the end of life. It is a useful adjuvant if pain is unresponsive to continuous
      infusion opioids or if rapidly escalating doses of opioids are required.

PMID- 17185398
TI  - Needle phobia and stress-reducing medical devices in pediatric and adult
      chemotherapy patients.
AB  - Needle phobia--fear of medical devices--is a significant problem in pediatric and
      adult chemotherapy patients. Stress-reducing medical devices is a new, effective
      cognitive therapy for needle phobia. Twenty-five pediatric and 25 adult
      chemotherapy patients were randomly exposed to conventional or stress-reducing
      decorated butterfly needles and syringes. Emotional stress responses were
      determined with the Visual Aversion Scale, Visual Analogue Fear Scale, Visual
      Analogue Anxiety Scale, and Visual Overall Stress Score for each needle and
      syringe design. Sixty-eight percent of the pediatric and 52% of the adult
      patients were overtly needle phobic, but children demonstrated significantly more
      aversion and stress (P < .001). Stress-reducing medical devices effectively and
      significantly reduced aversion, anxiety, fear, and overall stress, and were 76%
      effective in preventing overt needle phobia in children and 92% effective in
      adults (P < .001). One hundred percent of children and adults felt that stress
      reducing medical devices should be available in chemotherapy clinics. Needle
      phobia and stress in pediatric and adult chemotherapy patients are significantly
      reduced by the use of stress-reducing medical devices.

PMID- 17185400
TI  - The use of herbal therapies in pediatric oncology patients: treating symptoms of
      cancer and side effects of standard therapies.
AB  - Complementary and alternative medicine is increasing in use in the pediatric
      oncology population. Although there is a multitude of herbal therapies used, the
      focus of this article is a review of the literature addressing some herbal
      therapies used to treat the symptoms of cancer and side effects of traditional
      methods of treatment. Ginger is used in the treatment of nausea and vomiting. St.
      John's wort is successful in treating depression and anxiety. Echinacea is used
      as an immunostimulant. Herbal therapies in the pediatric oncology population are
      usually initiated and managed by parents. Many herbal therapies are beneficial,
      but some potential herb-drug interactions should be considered. This poses a
      challenge to the oncology nurse because herbal treatments are managed by the
      parents and pharmaceuticals are managed by the practitioner. Educating the
      patient, family, and practitioner is important in ensuring a thorough health
      history assessment and, subsequently, safe and effective herbal and
      pharmacological therapies.

PMID- 17185401
TI  - The role of oral glutamine in pediatric bone marrow transplant.
AB  - Oral mucositis continues to be a common and debilitating side effect of the
      conditioning regimens that use high-dose chemotherapy with or without radiation
      for pediatric bone marrow transplantation. Limited interventions have
      demonstrated success in preventing or treating it. Administration of glutamine,
      which is a nitrogen-rich amino acid found in the body, has emerged as a possible
      method of preventing oral mucositis in patients undergoing bone marrow
      transplantation. Numerous studies have looked at the effects of oral glutamine
      supplementation during bone marrow transplant. The purpose of this article is to
      describe glutamine and how it functions, review the literature regarding the use
      of oral glutamine in the prevention of oral mucositis in bone marrow
      transplantion, discuss the administration concerns related to the pediatric
      setting, and stress the importance of the nurse's role at the bedside. Nurses
      working in pediatric bone marrow transplant play a key role in the assessment of
      oral mucositis, administration of oral glutamine, and education of the patient
      and family.

PMID- 17185402
TI  - Outpatient transfusion practice and factors leading to inpatient transfusion in a
      pediatric hematology/oncology program.
AB  - Oral mucositis continues to be a common and debilitating side effect of the
      conditioning regimens that use high-dose chemotherapy with or without radiation
      for pediatric bone marrow transplantation. Limited interventions have
      demonstrated success in preventing or treating it. Administration of glutamine,
      which is a nitrogen-rich amino acid found in the body, has emerged as a possible
      method of preventing oral mucositis in patients undergoing bone marrow
      transplantation. Numerous studies have looked at the effects of oral glutamine
      supplementation during bone marrow transplant. The purpose of this article is to
      describe glutamine and how it functions, review the literature regarding the use
      of oral glutamine in the prevention of oral mucositis in bone marrow
      transplantion, discuss the administration concerns related to the pediatric
      setting, and stress the importance of the nurse's role at the bedside. Nurses
      working in pediatric bone marrow transplant play a key role in the assessment of
      oral mucositis, administration of oral glutamine, and education of the patient
      and family.

PMID- 17185403
TI  - For the ZDF rat, "Breaking up is hard to do": dissociation of the GK:GKRP
      complex.

PMID- 17185405
TI  - A kinetic model of bone marrow neutrophil production that characterizes late
      phenotypic maturation.
AB  - Acute inflammatory stimuli rapidly mobilize neutrophils from the bone marrow by
      shortening postmitotic maturation time and releasing younger neutrophils;
      however, the kinetics of this change in maturation time remains unknown. We
      propose a kinetic model that examines the rate of change in neutrophil average
      age at exit from the bone marrow during active mobilization to quantify this
      response and use this model to examine the temporal profile of late neutrophil
      phenotypic maturation. Total and CD10(-)/CD16(low) circulating neutrophils were
      quantified in cardiac surgery patients during extracorporeal circulation (ECC).
      Net growth in the circulating neutrophil pool occurred during the procedural
      (0.04 +/- 0.02 x 10(9) x l(-1) x min(-1)), warming (0.14 +/- 0.02 x 10(9) x l(-1)
      x min(-1)), and weaning (0.12 +/- 0.06 x 10(9) x l(-1) x min(-1)) phases of ECC.
      When applied to our differential equation mathematical model, these results
      predict that neutrophil average age at exit from the bone marrow decreased
      continually during ECC, resulting in average neutrophil release 8.44 +/- 2.20 h
      earlier during the weaning phase than at the beginning of ECC sampling. Modeling
      of concurrent changes in CD10(-)/CD16(low) neutrophil numbers indicates that CD10
      expression is directly related to neutrophil mean age and predicts that the
      proportion of mobilizable postmitotic neutrophils that are CD10(+) increases from
      64 to 81% during these sampled 8.4 h of maturation.

PMID- 17185404
TI  - Cerebral energetic effects of creatine supplementation in humans.
AB  - There has been considerable interest in the use of creatine (Cr) supplementation
      to treat neurological disorders. However, in contrast to muscle physiology, there
      are relatively few studies of creatine supplementation in the brain. In this
      report, we use high-field MR (31)P and (1)H spectroscopic imaging of human brain
      with a 7-day protocol of oral Cr supplementation to examine its effects on
      cerebral energetics (phosphocreatine, PCr; ATP) and mitochondrial metabolism (N
      acetyl aspartate, NAA; and Cr). We find an increased ratio of PCr/ATP (day 0,
      0.80 +/- 0.10; day 7, 0.85 +/- 09), with this change largely due to decreased
      ATP, from 2.7 +/- 0.3 mM to 2.5 +/- 0.3 mM. The ratio of NAA/Cr also decreased
      (day 0, 1.32 +/- 0.17; day 7 1.18 +/- 0.13), primarily from increased Cr (9.6 +/-
      1.9 to 10.1 +/- 2.0 mM). The Cr-induced changes significantly correlated with the
      basal state, with the fractional increase in PCr/ATP negatively correlating with
      the basal PCr/ATP value (R = -0.74, P < 0.001). As NAA is a measure of
      mitochondrial function, there was also a significant negative correlation between
      basal NAA concentrations with the fractional change in PCr and ATP. Thus healthy
      human brain energetics is malleable and shifts with 7 days of Cr supplementation,
      with the regions of initially low PCr showing the largest increments in PCr.
      Overall, Cr supplementation appears to improve high-energy phosphate turnover in
      healthy brain and can result in either a decrease or an increase in high-energy
      phosphate concentrations.

PMID- 17185406
TI  - Nitric oxide pathway counteracts enhanced contraction to membrane depolarization
      in aortic rings of rats on high-sodium diet.
AB  - Vascular smooth muscle cell contraction and endothelium-dependent relaxation was
      evaluated in aortic rings isolated from weaned, 5-mo-old Sprague-Dawley rats fed
      a normal (NS; 0.8% NaCl) or high (HS; 8% NaCl) sodium diet. Arterial pressure was
      140 +/- 6 (NS) and 145 +/- 6 mmHg (HS). In endothelium-denuded rings, the
      response to phenylephrine (PE) was not modified by the sodium diet, while that of
      depolarizing agent KCl and intracellular calcium releasing agent caffeine
      increased in the HS group. When endothelium was preserved, PE-evoked contraction
      was reduced in both NS and HS groups, the contraction being yet lower in the HS
      group. This effect was partially obliterated by addition of N(G)-nitro-L-arginine
      methyl ester (L-NAME), independently of the sodium diet. Relaxation to ACh in
      intact rings and to sodium nitroprusside (SNP) and 8-bromoadenosine 3'5' cyclic
      guanosine monophosphate (8-BrcGMP) in the absence of endothelium was enhanced in
      rings isolated from HS rats. In addition, the dose-response curve to 8-BrcGMP was
      shifted to the right in the presence of iberiotoxin, an inhibitor of large
      conductance, voltage-dependent, and calcium-sensitive potassium channel (BK(Ca)).
      However, shift was more marked in rings from HS rats. Present results provide
      evidence that response of vascular smooth muscle cell to nitric oxide/cGMP
      related compounds is increased in HS rings and is associated with a greater
      activation of the repolarizing BK(Ca) channels. Such changes might counterbalance
      enhanced contractile response to membrane depolarization and thus participate in
      maintenance of arterial pressure in the present model of early and long-term HS
      feeding in rats.

PMID- 17185407
TI  - AT(1) and glutamatergic receptors in paraventricular nucleus support blood
      pressure during water deprivation.
AB  - Water deprivation activates sympathoexcitatory neurons in the paraventricular
      nucleus (PVN); however, the neurotransmitters that mediate this activation are
      unknown. To test the hypothesis that ANG II and glutamate are involved, effects
      on blood pressure (BP) of bilateral PVN microinjections of ANG II type 1 receptor
      (AT1R) antagonists, candesartan and valsartan, or the ionotropic glutamate
      receptor antagonist, kynurenate, were determined in urethane-anesthetized water
      deprived and water-replete male rats. Because PVN may activate sympathetic
      neurons via the rostral ventrolateral medulla (RVLM) and because PVN
      disinhibition increases sympathetic activity in part via increased drive of AT1R
      in the RVLM, candesartan was also bilaterally microinjected into the RVLM. Total
      blockade of the PVN with bilateral microinjections of muscimol, a GABA(A)
      agonist, decreased BP more (P < 0.05) in water-deprived (-29 +/- 8 mmHg) than in
      water-replete (-7 +/- 2 mmHg) rats, verifying that the PVN is required for BP
      maintenance during water deprivation. PVN candesartan slowly lowered BP by 7 +/-
      1 mmHg (P < 0.05). In water-replete rats, however, candesartan did not alter BP
      (1 +/- 1 mmHg). Valsartan also produced a slowly developing decrease in arterial
      pressure (-6 +/- 1 mmHg; P < 0.05) in water-deprived but not in water-replete (-1
      +/- 1 mmHg) rats. In water-deprived rats, PVN kynurenate rapidly decreased BP (
      19 +/- 3 mmHg), and the response was greater (P < 0.05) than in water-replete
      rats (-4 +/- 1 mmHg). Finally, as in PVN, candesartan in RVLM slowly decreased BP
      in water-deprived (-8 +/- 1 mmHg; P < 0.05) but not in water-replete (-3 +/- 1
      mmHg) rats. These data suggest that activation of AT(1) and glutamate receptors
      in PVN, as well as of AT1R in RVLM, contributes to BP maintenance during water
      deprivation.

PMID- 17185408
TI  - Model-projected mechanistic bases for sex differences in growth hormone
      regulation in humans.
AB  - Models of physiological systems facilitate rational experimental design,
      inference, and prediction. A recent construct of regulated growth hormone (GH)
      secretion interlinks the actions of GH-releasing hormone (GHRH), somatostatin
      (SRIF), and GH secretagogues (GHS) with GH feedback in the rat (Farhy LS,
      Veldhuis JD. Am J Physiol Regul Integr Comp Physiol 288: R1649-R1663, 2005). In
      contrast, no comparable formalism exists to explicate GH dynamics in any other
      species. The present analyses explore whether a unifying model structure can
      represent species- and sex-defined distinctions in the human and rodent. The
      consensus principle that GHRH and GHS synergize in vivo but not in vitro was
      explicable by assuming that GHS 1) evokes GHRH release from the brain, 2) opposes
      inhibition by SRIF both in the hypothalamus and on the pituitary gland, and 3)
      stimulates pituitary GH release directly and additively with GHRH. The gender
      selective principle that GH pulses are larger and more irregular in women than
      men was conferrable by way of 4) higher GHRH potency and 5) greater GHS efficacy.
      The overall construct predicts GHRH/GHS synergy in the human only in the presence
      of SRIF when the brain-pituitary nexus is intact, larger and more irregular GH
      pulses in women, and observed gender differences in feedback by GH and the single
      and paired actions of GHRH, GHS, and SRIF. The proposed model platform should
      enhance the framing and interpretation of novel clinical hypotheses and create a
      basis for interspecies generalization of GH-axis regulation.

PMID- 17185409
TI  - Mitochondrial function and nitric oxide metabolism are modified by enalapril
      treatment in rat kidney.
AB  - The renal and cardiac benefits of renin-angiotensin system (RAS) inhibition in
      hypertension exceed those attributable to blood pressure reduction, and seem to
      involve mitochondrial function changes. To investigate whether mitochondrial
      changes associated with RAS inhibition are related to changes in nitric oxide
      (NO) metabolism, four groups of male Wistar rats were treated during 2 wk with a
      RAS inhibitor, enalapril (10 mg x kg(-1) x day(-1); Enal), or a NO synthase (NOS)
      inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME) (1 mg x kg(-1) x day(
      1)), or both (Enal+L-NAME), or were untreated (control). Blood pressure and body
      weight were lower in Enal than in control. Electron transfer through complexes I
      to III and cytochrome oxidase activity were significantly lower, and uncoupling
      protein-2 content was significantly higher in kidney mitochondria isolated from
      Enal than in those from control. All of these changes were prevented by L-NAME
      cotreatment and were accompanied by a higher production/bioavailability of kidney
      NO. L-NAME abolished mitochondrial NOS activity but failed to inhibit extra
      mitochondrial kidney NOS, underscoring the relevance of mitochondrial NO in those
      effects of enalapril that were suppressed by L-NAME cotreatment. In Enal, kidney
      mitochondria H(2)O(2) production rate and MnSOD activity were significantly lower
      than in control, and these effects were not prevented by L-NAME cotreatment.
      These findings may clarify the role of NO in the interactions between RAS and
      mitochondrial metabolism and can help to unravel the mechanisms involved in renal
      protection by RAS inhibitors.

PMID- 17185410
TI  - Varicella-zoster vaccine virus: evolution in action.

PMID- 17185411
TI  - Identification and characterization of COPIa- and COPIb-type vesicle classes
      associated with plant and algal Golgi.
AB  - Coat protein I (COPI) vesicles arise from Golgi cisternae and mediate the
      recycling of proteins from the Golgi back to the endoplasmic reticulum (ER) and
      the transport of Golgi resident proteins between cisternae. In vitro studies have
      produced evidence for two distinct types of COPI vesicles, but the in vivo sites
      of operation of these vesicles remain to be established. We have used a
      combination of electron tomography and immunolabeling techniques to examine Golgi
      stacks and associated vesicles in the cells of the scale-producing alga
      Scherffelia dubia and Arabidopsis preserved by high-pressure freezing/freeze
      substitution methods. Five structurally distinct types of vesicles were
      distinguished. In Arabidopsis, COPI and COPII vesicle coat proteins as well as
      vesicle cargo molecules (mannosidase I and sialyltransferase-yellow fluorescent
      protein) were identified by immunogold labeling. In both organisms, the COPI-type
      vesicles were further characterized by a combination of six structural criteria:
      coat architecture, coat thickness, membrane structure, cargo staining, cisternal
      origin, and spatial distribution. Using this multiparameter structural approach,
      we can distinguish two types of COPI vesicles, COPIa and COPIb. COPIa vesicles
      bud exclusively from cis cisternae and occupy the space between cis cisternae and
      ER export sites, whereas the COPIb vesicles bud exclusively from medial- and
      trans-Golgi cisternae and are confined to the space around these latter
      cisternae. We conclude that COPIa vesicle-mediated recycling to the ER occurs
      only from cis cisternae, that retrograde transport of Golgi resident proteins by
      COPIb vesicles is limited to medial and trans cisternae, and that diffusion of
      periGolgi vesicles is restricted.

PMID- 17185412
TI  - Identification of the protein receptor binding site of botulinum neurotoxins B
      and G proves the double-receptor concept.
AB  - Botulinum neurotoxins (BoNTs) cause muscle paralysis by selectively cleaving core
      components of the vesicular fusion machinery within motoneurons. Complex
      gangliosides initially bind into a pocket that is conserved among the seven BoNTs
      and tetanus neurotoxin. Productive neurotoxin uptake also requires protein
      receptors. The interaction site of the protein receptor within the neurotoxin is
      currently unknown. We report the identification and characterization of the
      protein receptor binding site of BoNT/B and BoNT/G. Their protein receptors,
      synaptotagmins I and II, bind to a pocket at the tip of their H(CC) (C-terminal
      domain of the C-terminal fragment of the heavy chain) that corresponds to the
      unique second carbohydrate binding site of tetanus neurotoxin, the sialic acid
      binding site. Substitution of amino acids in this region impaired binding to
      synaptotagmins and drastically decreased toxicity at mouse phrenic nerve
      preparations; CD-spectroscopic analyses evidenced that the secondary structure of
      the mutated neurotoxins was unaltered. Deactivation of the synaptotagmin binding
      site by single mutations led to virtually inactive BoNT/B and BoNT/G when assayed
      at phrenic nerve preparations of complex-ganglioside-deficient mice. Analogously,
      a BoNT B mutant with deactivated ganglioside and synaptotagmin binding sites
      lacked appreciable activity at wild-type mouse phrenic nerve preparations. Thus,
      these data exclude relevant contributions of any cell surface molecule other than
      one ganglioside and one protein receptor to the entry process of BoNTs, which
      substantiates the double-receptor concept. The molecular characterization of the
      synaptotagmin binding site provides the basis for designing a novel class of
      potent binding inhibitors.

PMID- 17185413
TI  - Isolation and functional characterization of murine prostate stem cells.
AB  - The ability to isolate prostate stem cells is essential to explore their role in
      prostate development and disease. In vitro prostate colony- and sphere-forming
      assays were used to quantitatively measure murine prostate stem/progenitor cell
      enrichment and self-renewal. Cell surface markers were screened for their ability
      to positively or negatively enrich for cells with enhanced growth potential in
      these assays. Immunohistochemical and FACS analyses demonstrate that specific
      cell surface markers can be used to discriminate prostate stromal (CD34(+)),
      luminal epithelial (CD24(+)CD49f(-)), basal epithelial (CD24(+)CD49f(+)),
      hematopoietic (CD45(+), Ter119(+)), and endothelial (CD31(+)) lineages. Sorting
      for cells with a CD45(-)CD31(-)Ter119(-)Sca-1(+)CD49f(+) antigenic profile
      results in a 60-fold enrichment for colony- and sphere-forming cells. These cells
      can self-renew and expand to form spheres for many generations and can
      differentiate to produce prostatic tubule structures containing both basal and
      luminal cells in vivo. These cells also localize to the basal cell layer within
      the region of the gland that is proximal to the urethra, which has been
      identified as the prostate stem cell niche. Prostate stem cells can be isolated
      to a purity of up to 1 in 35 by using this antigenic profile. The remarkable
      similarity in cell surface profile between prostate and mammary gland stem cells
      suggests these markers may be conserved among epithelial stem cell populations.

PMID- 17185414
TI  - Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of
      NPM-ALK.
AB  - Constitutive overexpression and activation of NPM-ALK fusion protein
      [t(2:5)(p23;q35)] is a key oncogenic event that drives the survival and
      proliferation of anaplastic large-cell lymphomas (ALCLs). We have identified a
      highly potent and selective small-molecule ALK inhibitor, NVP-TAE684, which
      blocked the growth of ALCL-derived and ALK-dependent cell lines with IC(50)
      values between 2 and 10 nM. NVP-TAE684 treatment resulted in a rapid and
      sustained inhibition of phosphorylation of NPM-ALK and its downstream effectors
      and subsequent induction of apoptosis and cell cycle arrest. In vivo, NVP-TAE684
      suppressed lymphomagenesis in two independent models of ALK-positive ALCL and
      induced regression of established Karpas-299 lymphomas. NVP-TAE684 also induced
      down-regulation of CD30 expression, suggesting that CD30 may be used as a
      biomarker of therapeutic NPM-ALK kinase activity inhibition.

PMID- 17185415
TI  - Amyloid precursor protein overexpression depresses excitatory transmission
      through both presynaptic and postsynaptic mechanisms.
AB  - Overexpression of the amyloid precursor protein (APP) in hippocampal neurons
      leads to elevated beta-amyloid peptide (Abeta) production and consequent
      depression of excitatory transmission. The precise mechanisms underlying APP
      induced synaptic depression are poorly understood. Uncovering these mechanisms
      could provide insight into how neuronal function is compromised before cell death
      during the early stages of Alzheimer's disease. Here we verify that APP up
      regulation leads to depression of transmission in cultured hippocampal autapses;
      and we perform whole-cell recording, FM imaging, and immunocytochemistry to
      identify the specific mechanisms accounting for this depression. We find that APP
      overexpression leads to postsynaptic silencing through a selective reduction of
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated
      currents. This effect is likely mediated by Abeta because expression of mutant
      APP incapable of producing Abeta did not depress transmission. In addition,
      although we eliminate presynaptic silencing as a mechanism underlying APP
      mediated inhibition of transmission, we did observe an Abeta-induced presynaptic
      deficit in vesicle recycling with sustained stimulation. These findings
      demonstrate that APP elevation disrupts both presynaptic and postsynaptic
      compartments.

PMID- 17185416
TI  - Ethanol prevents development of destructive arthritis.
AB  - Environmental factors are thought to play a major role in the development of
      rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the
      role of ethanol intake on the propensity to develop chronic arthritis. Collagen
      type II-immunized mice were given water or water containing 10% (vol/vol) ethanol
      or its metabolite acetaldehyde. Their development of arthritis was assessed, as
      well as the impact of ethanol on leukocyte migration and activation of
      intracellular transcription factors. Mice exposed daily to this dose of ethanol
      did not display any liver toxicity, and the development of erosive arthritis was
      almost totally abrogated. In contrast, the antibody-mediated effector phase of
      collagen-induced arthritis was not influenced by ethanol exposure. Also, the
      major ethanol metabolite, acetaldehyde, prevented the development of arthritis.
      This antiinflammatory and antidestructive property of ethanol was mediated by (i)
      down-regulation of leukocyte migration and (ii) up-regulation of testosterone
      secretion, with the latter leading to decreased NF-kappaB activation. We conclude
      that low but persistent ethanol consumption delays the onset and halts the
      progression of collagen-induced arthritis by interaction with innate immune
      responsiveness.

PMID- 17185417
TI  - The zinc-finger antiviral protein recruits the RNA processing exosome to degrade
      the target mRNA.
AB  - Zinc-finger antiviral protein (ZAP) is a host antiviral factor that specifically
      inhibits the replication of Moloney murine leukemia virus (MLV) and Sindbis virus
      (SIN) by preventing accumulation of the viral mRNA in the cytoplasm. In previous
      studies, we demonstrated that ZAP directly binds to its specific target mRNAs. In
      this article, we provide evidence indicating that ZAP recruits the RNA processing
      exosome to degrade the target RNA. ZAP comigrated with the exosome in sucrose or
      glycerol velocity gradient centrifugation. Immunoprecipitation of ZAP
      coprecipitated the exosome components. In vitro pull-down assays indicated that
      ZAP directly interacted with the exosome component hRrp46p and that the binding
      region of ZAP was mapped to amino acids 224-254. Depletion of the exosome
      component hRrp41p or hRrp46p with small interfering RNA significantly reduced
      ZAP's destabilizing activity. These findings suggest that ZAP is a trans-acting
      factor that modulates mRNA stability.

PMID- 17185418
TI  - IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated
      nuclear factor in vivo.
AB  - Recent studies indicate that IL-1alpha functions intracellularly in pathways
      independent of its cell surface receptors by translocating to the nucleus and
      regulating transcription. Similarly, the chromatin-associated protein HMGB1 acts
      as both a nuclear factor and a secreted proinflammatory cytokine. Here, we show
      that IL-33, an IL-1-like cytokine that signals via the IL-1 receptor-related
      protein ST2 and induces T helper type 2-associated cytokines, is an endothelium
      derived, chromatin-associated nuclear factor with transcriptional repressor
      properties. We found that IL-33 is identical to NF-HEV, a nuclear factor
      preferentially expressed in high endothelial venules (HEV), that we previously
      characterized. Accordingly, in situ hybridization demonstrated that endothelial
      cells constitute a major source of IL-33 mRNA in chronically inflamed tissues
      from patients with rheumatoid arthritis and Crohn's disease. Immunostaining with
      three distinct antisera, directed against the N-terminal part and IL-1-like C
      terminal domain, revealed that IL-33 is a heterochromatin-associated nuclear
      factor in HEV endothelial cells in vivo. Association of IL-33 with
      heterochromatin was also observed in human and mouse cells under living
      conditions. In addition, colocalization of IL-33 with mitotic chromatin was
      noted. Nuclear localization, heterochromatin-association, and targeting to
      mitotic chromosomes were all found to be mediated by an evolutionarily conserved
      homeodomain-like helix-turn-helix motif within the IL-33 N-terminal part.
      Finally, IL-33 was found to possess transcriptional repressor properties,
      associated with the homeodomain-like helix-turn-helix motif. Together, these data
      suggest that, similarly to IL1alpha and HMGB1, IL-33 is a dual function protein
      that may function as both a proinflammatory cytokine and an intracellular nuclear
      factor with transcriptional regulatory properties.

PMID- 17185419
TI  - Mechanism of tRNA-dependent editing in translational quality control.
AB  - Protein synthesis requires the pairing of amino acids with tRNAs catalyzed by the
      aminoacyl-tRNA synthetases. The synthetases are highly specific, but errors in
      amino acid selection are occasionally made, opening the door to inaccurate
      translation of the genetic code. The fidelity of protein synthesis is maintained
      by the editing activities of synthetases, which remove noncognate amino acids
      from tRNAs before they are delivered to the ribosome. Although editing has been
      described in numerous synthetases, the reaction mechanism is unknown. To define
      the mechanism of editing, phenylalanyl-tRNA synthetase was used to investigate
      different models for hydrolysis of the noncognate product Tyr-tRNA(Phe).
      Deprotonation of a water molecule by the highly conserved residue betaHis-265, as
      proposed for threonyl-tRNA synthetase, was excluded because replacement of this
      and neighboring residues had little effect on editing activity. Model building
      suggested that, instead of directly catalyzing hydrolysis, the role of the
      editing site is to discriminate and properly position noncognate substrate for
      nucleophilic attack by water. In agreement with this model, replacement of
      certain editing site residues abolished substrate specificity but only reduced
      the catalytic efficiency of hydrolysis 2- to 10-fold. In contrast, substitution
      of the 3'-OH group of tRNA(Phe) severely impaired editing and revealed an
      essential function for this group in hydrolysis. The phenylalanyl-tRNA synthetase
      editing mechanism is also applicable to threonyl-tRNA synthetase and provides a
      paradigm for synthetase editing.

PMID- 17185420
TI  - Sequential structure of neocortical spontaneous activity in vivo.
AB  - Even in the absence of sensory stimulation, the neocortex shows complex
      spontaneous activity patterns, often consisting of alternating "DOWN" states of
      generalized neural silence and "UP" states of massive, persistent network
      activity. To investigate how this spontaneous activity propagates through
      neuronal assemblies in vivo, we simultaneously recorded populations of 50-200
      cortical neurons in layer V of anesthetized and awake rats. Each neuron displayed
      a virtually unique spike pattern during UP states, with diversity seen amongst
      both putative pyramidal cells and interneurons, reflecting a complex but
      stereotypically organized sequential spread of activation through local cortical
      networks. Spike timing was most precise during the first approximately 100 ms
      after UP state onset, and decayed as UP states progressed. A subset of UP states
      propagated as traveling waves, but waves passing a given point in either
      direction initiated similar local sequences, suggesting local networks as the
      substrate of sequential firing patterns. A search for repeating motifs indicated
      that their occurrence and structure was predictable from neurons' individual
      latencies to UP state onset. We suggest that these stereotyped patterns arise
      from the interplay of intrinsic cellular conductances and local circuit
      properties.

PMID- 17185421
TI  - LIM-only protein, CRP2, switched on smooth muscle gene activity in adult cardiac
      myocytes.
AB  - Smooth muscle alpha-actin gene activity appears in promyocardial cells well
      before cardiac myocyte differentiation and is down-regulated during the onset of
      rhythmic contractility and cardiac morphogenesis. The levels of LIM-only CRP2
      correlated well with smooth muscle gene activity. Cardiomyocyte-specific
      expression of CRP2 in transgenic mice showed robust expression of smooth muscle
      cell-specific transcripts and protein filaments in the adult heart. Protein
      transduction of a recombinant CRP2 protein, fused to the protein transduction
      domain of HIV, into neonatal heart cells induced de novo synthesis of smooth
      muscle cell-specific transcripts and proteins. The LIM zinc fingers in CRP2 were
      found to collaborate with Brg1 of the SNF/SWI complexes, recruited serum response
      factor, and remodeled smooth muscle target gene chromatin through histone
      acetylation. CRP2 may have a cytoskeletal role, but as a nuclear protein, CRP2
      acted as a potent transcription coadaptor that remodeled silent cardiac myocyte
      chromatin and directed serum response factor-dependent smooth muscle gene
      activity.

PMID- 17185422
TI  - Mapping protein collapse with single-molecule fluorescence and kinetic
      synchrotron radiation circular dichroism spectroscopy.
AB  - We have used the combination of single-molecule Forster resonance energy transfer
      and kinetic synchrotron radiation circular dichroism experiments to probe the
      conformational ensemble of the collapsed unfolded state of the small cold shock
      protein CspTm under near-native conditions. This regime is physiologically most
      relevant but difficult to access experimentally, because the equilibrium signal
      in ensemble experiments is dominated by folded molecules. Here, we avoid this
      problem in two ways. One is the use of single-molecule Forster resonance energy
      transfer, which allows the separation of folded and unfolded subpopulations at
      equilibrium and provides information on long-range intramolecular distance
      distributions. From experiments with donor and acceptor chromophores placed at
      different positions within the chain, we find that the distance distributions in
      unfolded CspTm agree surprisingly well with a Gaussian chain not only at high
      concentrations of denaturant, where the polypeptide chain is expanded, but also
      at low denaturant concentrations, where the chain is collapsed. The second,
      complementary approach is synchrotron radiation circular dichroism spectroscopy
      of collapsed unfolded molecules transiently populated with a microfluidic device
      that enables rapid mixing. The results indicate a beta-structure content of the
      collapsed unfolded state of approximately 20% compared with the folded protein.
      This suggests that collapse can induce secondary structure in an unfolded state
      without interfering with long-range distance distributions characteristic of a
      random coil, which were previously found only for highly expanded unfolded
      proteins.

PMID- 17185423
TI  - Cognitive assessment of children at age 2(1/2) years after maternal fish oil
      supplementation in pregnancy: a randomised controlled trial.
AB  - OBJECTIVE: To assess the effects of antenatal omega 3 long-chain polyunsaturated
      fatty acid (n-3 LC PUFA) on cognitive development in a cohort of children whose
      mothers received high-dose fish oil in pregnancy. DESIGN: A double-blind
      randomised placebo-controlled trial. SETTING: Perth, Western Australia,
      Australia. PATIENTS: 98 pregnant women received the supplementation from 20
      weeks' gestation until delivery. Their infants (n = 72) were assessed at age
      2(1/2) years. INTERVENTIONS: Fish oil (2.2 g docosahexaenoic acid (DHA) and 1.1 g
      eicosapentaenoic acid (EPA)/day) or olive oil from 20 weeks' gestation until
      delivery. OUTCOME MEASURES: Effects on infant growth and developmental quotients
      (Griffiths Mental Development Scales), receptive language (Peabody Picture
      Vocabulary Test) and behaviour (Child Behaviour Checklist). RESULTS: Children in
      the fish oil-supplemented group (n = 33) attained a significantly higher score
      for eye and hand coordination (mean ((SD) score 114 (10.2)) than those in the
      placebo group (n = 39, mean score 108 (SD 11.3); p = 0.021, adjusted p = 0.008).
      Eye and hand coordination scores correlated with n-3 PUFA levels in cord blood
      erythrocytes (EPA: r = 0.320, p = 0.007; DHA: r = 0.308, p = 0.009) and inversely
      correlated with n-6 PUFA (arachidonic acid 20:4n-6: r = -0.331, p = 0.005).
      Growth measurements in the two groups were similar at age 2(1/2) years.
      CONCLUSION: Maternal fish oil supplementation during pregnancy is safe for the
      fetus and infant, and may have potentially beneficial effects on the child's eye
      and hand coordination. Further studies are needed to determine the significance
      of this finding.

PMID- 17185424
TI  - Quick identification of febrile neonates with low risk for serious bacterial
      infection: an observational study.
AB  - OBJECTIVE: To examine the possible usefulness of simple and quick criteria for
      identifying febrile neonates with low risk for serious bacterial infection (SBI).
      DESIGN: All febrile neonates who were admitted between August 1998 and August
      2003 to the Pediatric Emergency Department, HaEmek Medical Center, Afula, Israel,
      and to the Poriya Hospital, Tiberias, Israel, were included in the study. The
      recommended evaluation of each neonate included details of medical history and a
      complete physical examination, including blood culture, erythrocyte sedimentation
      rate (ESR), white cell count (WBC), and analysis and culture of urine and
      cerebrospinal fluid. Other tests were carried out as necessary. Patients who met
      all the following criteria were considered to have low risk for SBI: (1)
      unremarkable medical history; (2) good appearance; (3) no focal physical signs of
      infection; (4) ESR <30 mm at the end of the first hour; (5) WBC 5000-15
      000/mm(3); (6) a normal urine analysis by the dipstick method. RESULTS: Complete
      data were available for 386 neonates. SBI was documented in 108 (28%) neonates,
      of whom 14% had a urinary tract infection, 9.3% had acute otitis media, 2.3% had
      pneumonia, 1.3% had cellulitis, 0.5% had bacterial meningitis and 0.5% had
      bacterial gastroenteritis. The overall incidence of SBI was 1 in 166 (0.6%)
      neonates who fulfilled the criteria compared with 107 in 220 (48.6%) in the
      neonates who did not fulfil the criteria (p<0.001). The negative predictive value
      for SBI of the combination of the low-risk criteria was 99.4% (95% confidence
      interval 99.35% to 99.45%). CONCLUSIONS: Fulfillment of the criteria for low risk
      might be a reliable and useful tool for excluding SBI in febrile neonates.

PMID- 17185425
TI  - Nasal trauma due to nasal continuous positive airway pressure in newborns.

PMID- 17185426
TI  - Is there a place for "drive thru" management of neonatal fever? Not yet!

PMID- 17185427
TI  - Superior sternal cleft, cutaneous, and airway haemangiomas.

PMID- 17185428
TI  - Pulse oximetry for monitoring infants in the delivery room: a review.

PMID- 17185429
TI  - H-type tracheo-oesophageal fistula.

PMID- 17185430
TI  - Necrosis of the left buttock as a complication of umbilical catheterisation in
      neonatal resuscitation.

PMID- 17185431
TI  - Peripheral oxygenation in term neonates.
AB  - The aim of this study was to analyse changes in peripheral oxygenation in healthy
      term neonates within the first week of life with near-infrared spectroscopy and
      venous occlusion. Oxygen delivery did not change with increasing age. Oxygen
      consumption and fractional oxygen extraction increased, whereas tissue
      oxygenation index decreased with increasing age.

PMID- 17185432
TI  - Management of fetal growth restriction.
AB  - Fetal growth restriction (FGR) is challenging because of the difficulties in
      reaching a definitive diagnosis of the cause and planning management. FGR is
      associated not only with a marked increased risk in perinatal mortality and
      morbidity but also with long-term outcome risks. Combinations of fetal biometry,
      amniotic fluid volume, heart rate patterns, arterial and venous Doppler, and
      biophysical variables allow a comprehensive fetal evaluation of FGR. However, no
      evidence supports that the use of cardiotocography or the biophysical profile
      improves perinatal outcome. Therefore, obstetricians aim to identify fetuses with
      early FGR so delivery can be planned according to gestational age and severity of
      the condition. The balance of risks and the need for the availability of services
      mean that the involvement of neonatologists in FGR management is vital. In this
      review, the focus is on the pathophysiology and management of FGR caused by
      placental diseases.

PMID- 17185433
TI  - Antenatal risk factors, cytokines and the development of atopic disease in early
      childhood.
AB  - Atopic diseases are complex entities influenced by an array of risk factors,
      including genetic predisposition, environmental allergens, antenatal exposures,
      infections and psychosocial factors. One proposed mechanism by which these risk
      factors contribute to the development of atopic disease is through changes in the
      production of T helper cell type 1 (Th1) and T helper cell type 2 (Th2)
      cytokines. The objectives of this review are to discuss antenatal exposures that
      are associated with paediatric atopic diseases, to discuss the influence of the
      intrauterine environment on neonatal immune responses, to provide an overview of
      the Th1 and Th2 pathways and how they relate to atopic disease, and to summarise
      our current understanding of the association between cytokine responses in cord
      blood and the development of atopic disease in early childhood.

PMID- 17185435
TI  - John Whitridge Williams, MD (1866-1931) of Baltimore: pioneer of academic
      obstetrics.
AB  - Williams was the founder of academic obstetrics in the United States and with his
      textbook was the recognised leader of this discipline in America during the first
      30 years of the 20th century.

PMID- 17185434
TI  - Neonatal anthropometric charts: what they are, what they are not.

PMID- 17185436
TI  - Magnetic resonance imaging measurement of fetal lung volume does not match
      postnatal survival.

PMID- 17185437
TI  - Nasopharyngeal aspiration for diagnosis of pulmonary tuberculosis.
AB  - BACKGROUND: Confirmation of pulmonary tuberculosis (PTB) in young children is
      difficult as they seldom expectorate sputum. AIM: To compare sputa obtained by
      nasopharyngeal aspiration and by sputum induction for staining and culture of
      Mycobacterium tuberculosis. PATIENTS AND METHODS: Patients from Mulago Hospital,
      Kampala with symptoms suggestive of PTB were considered for inclusion in the
      study. Those with a positive tuberculin test and/or a chest radiograph compatible
      with tuberculosis were recruited. Infection with human immunodeficiency virus
      (HIV) was confirmed by duplicate enzyme-labelled immunosorbent assay or in
      children <15 months by polymerase chain reaction (PCR). Direct PCR was undertaken
      on 82 nasopharyngeal aspirates. RESULTS: Of 438 patients referred, 94 were
      recruited over a period of 5 months. Median (range) age was 48 (4-144) months. Of
      63 patients tested, 69.8% were infected with HIV. Paired and uncontaminated
      culture results were available for 88 patients and smear results for 94 patients.
      Nasopharyngeal aspirates were smear-positive in 8.5% and culture-positive in
      23.9%. Induced sputa were smear-positive in 9.6% and culture positive in 21.6%.
      Overall, 10.6% were smear-positive, 25.5% were culture-positive and 26.6% had
      smear and/or culture confirmed tuberculosis. Direct PCR on nasopharyngeal
      aspirates had a sensitivity of 62% and specificity of 98% for confirmation of
      culture-positive tuberculosis. CONCLUSIONS: Nasopharyngeal aspiration is a
      useful, safe and low-technology method for confirmation of PTB and, like sputum
      induction, can be undertaken in outpatient clinics.

PMID- 17185438
TI  - New combination vaccines still need a boost.

PMID- 17185439
TI  - The nomad testis.

PMID- 17185440
TI  - Are children really safeguarded in the UK health service?

PMID- 17185441
TI  - Emergency care for children--the next steps.

PMID- 17185442
TI  - Treating low-risk febrile neutropenia: Jenny's story.

PMID- 17185443
TI  - Neonatal tetanus in Nigeria: does it still pose a major threat to neonatal
      survival?

PMID- 17185444
TI  - Acute cerebellitis with hydrocephalus and brainstem compression.

PMID- 17185445
TI  - Implementation of the healthcare recommendations arising from the Victoria
      Climbie report.

PMID- 17185446
TI  - Ankyloblepharon filiforme adnatum.
AB  - Two cases of a rare congenital eyelid abnormality, ankyloblepharon filiforme
      adnatum, are presented, and novel aspects of treatment, associations and
      classification are discussed.

PMID- 17185447
TI  - Four candles. Original perspectives and insights into 18th century hospital child
      healthcare.
AB  - It has only recently been recognised that for more than a century before the
      opening of Great Ormond Street Hospital for Children (1852) children were treated
      and even admitted in English Voluntary Hospitals. Among the earliest English 18th
      century records, that contain the patient's age, are those found at the
      Northampton General Hospital within an archive dating from its foundation as the
      Northampton Infirmary in 1744. They afford a fascinating glimpse into both
      inpatient and outpatient child health. Although there are no medical notes as
      such, the hospital archive has recently rediscovered 1743 statutes, contemporary
      patient literature entitled Some Friendly Advice to a Patient (written by the
      Northampton Infirmary's founding physician Dr (later Sir) James Stonhouse),
      minute books, contemporary engravings of the outside and inside of the hospital
      and inpatient menus. Thus we can speculate with a high degree of certainty as to
      what would be the then current infirmary environment and treatments for
      illustrative examples of the children seen in the period 1744-45 (two inpatients
      and two outpatients). Interestingly one of the inpatient cases, Elizabeth Ager, a
      child with fever, was admitted against the infirmary regulations, suggesting
      already a stretching of boundaries in favour of paediatric admissions. This paper
      gives a flavour of 18th century hospital child healthcare in an era before the
      formal recognition of paediatrics as a medical specialty and preceding by more
      than a century the construction of specialist provision through the foundation of
      the first children's hospitals.

PMID- 17185448
TI  - The shifting sands of research ethics and governance: effect on research in
      paediatrics.
AB  - Basic principles governing the ethical conduct of research have not changed but
      recent years have seen the burgeoning of bureaucracy to support and monitor
      research ethics and governance. More changes are planned, and the effect of the
      proposed changes on paediatric research are examined and broadly welcomed.

PMID- 17185449
TI  - A paper that changed my practice: S McKenzie. Cough but is it asthma? Arch Dis
      Child 1994;70:1-2.
AB  - Most doctors can identify key papers that have influenced their approach to the
      management of a particular clinical problem, although sometimes the gestation
      period of this effect can be very prolonged. In this short review I discuss the
      effects of a seminal paper by Sheila Mackenzie from the early 1990s on my current
      approach to the diagnosis and management of chronic cough in children.

PMID- 17185450
TI  - Why breast feeding fails.
AB  - BACKGROUND: Vanessa is a 34-year-old lawyer married to a police officer. Her
      first baby was born after a perfect pregnancy and labour until fetal distress
      necessitated an easy Ventouse extraction late in the second stage. Baby F had
      normal Apgar scores and weighed 2920 g. This paper records a conversation between
      Vanessa (V) and her father (F) about breast feeding.

PMID- 17185451
TI  - A survey of palivizumab for infants with cystic fibrosis in the UK.

PMID- 17185452
TI  - Determining the true prevalence of autistic spectrum disorders.

PMID- 17185453
TI  - Positive benefit of postnatal treatment in congenital toxoplasmosis.

PMID- 17185454
TI  - A newborn screening programme for congenital toxoplasmosis in the setting of a
      country with less income.

PMID- 17185455
TI  - Exposure to latex in schools.

PMID- 17185456
TI  - Was "variations of reproductive development" considered?

PMID- 17185457
TI  - Water intoxication and the heat wave.

PMID- 17185458
TI  - Is the heat wave increasing the number of falls from open windows among children?

PMID- 17185459
TI  - The HIV code.

PMID- 17185460
TI  - Molecular basis of glutathione reductase deficiency in human blood cells.
AB  - Hereditary glutathione reductase (GR) deficiency was found in only 2 cases when
      testing more than 15 000 blood samples. We have investigated the blood cells of 2
      patients (1a and 1b) in a previously described family suffering from favism and
      cataract and of a novel patient (2) presenting with severe neonatal jaundice. Red
      blood cells and leukocytes of the patients in family 1 did not contain any GR
      activity, and the GR protein was undetectable by Western blotting. Owing to a
      2246-bp deletion in the patients' DNA, translated GR is expected to lack almost
      the complete dimerization domain, which results in unstable and inactive enzyme.
      The red blood cells from patient 2 did not exhibit GR activity either, but the
      patient's leukocytes contained some residual activity that correlated with a weak
      protein expression. Patient 2 was found to be a compound heterozygote, with a
      premature stop codon on one allele and a substitution of glycine 330, a highly
      conserved residue in the superfamily of NAD(P)H-dependent disulfide reductases,
      into alanine on the other allele. Studies on recombinant GR G330A revealed a
      drastically impaired thermostability of the protein. This is the first
      identification of mutations in the GR gene causing clinical GR deficiency.

PMID- 17185461
TI  - NF-kappaB-independent down-regulation of XIAP by bortezomib sensitizes HL B cells
      against cytotoxic drugs.
AB  - The proteasome inhibitor bortezomib has been shown to possess promising antitumor
      activity and significant efficacy against a variety of malignancies. Different
      studies demonstrated that bortezomib breaks the chemoresistance in different
      tumor cells basically by altering nuclear factor-kappaB (NF-kappaB) activity. NF
      kappaB has been shown to be constitutively active in most primary Hodgkin-Reed
      Sternberg (H-RS) cells in lymph node sections and in Hodgkin lymphoma (HL) cell
      lines and was suggested to be a central molecular switch in apoptosis resistance
      in HL. Here we report a bimodal effect of bortezomib in HL cells. Whereas high
      dose bortezomib induced direct cytotoxicity that correlated with decreased NF
      kappaB activity, low-dose bortezomib sensitized HL cells against a variety of
      cytotoxic drugs without altering NF-kappaB action. Strikingly, bortezomib induced
      marked XIAP down-regulation at the posttranslational level that was independent
      of the NF-kappaB status. Similarly, RNA interference (RNAi)-mediated XIAP down
      regulation generated susceptibility to cytostatic agents. The results identify
      XIAP as an NF-kappaB-independent target of bortezomib action that controls the
      chemoresistant phenotype of HL cells.

PMID- 17185462
TI  - CBFB-MYH11 hinders early T-cell development and induces massive cell death in the
      thymus.
AB  - Recent studies suggest that the chromosome 16 inversion, associated with acute
      myeloid leukemia M4Eo, takes place in hematopoietic stem cells. If this is the
      case, it is of interest to know the effects of the resulting fusion gene, CBFB
      MYH11, on other lineages. Here we studied T-cell development in mice expressing
      Cbfb-MYH11 and compared them with mice compound-heterozygous for a Cbfb null and
      a hypomorphic GFP knock-in allele (Cbfb(-/GFP)), which had severe Cbfb
      deficiency. We found a differentiation block at the DN1 stage of thymocyte
      development in Cbfb-MYH11 knock-in chimeras. In a conditional knock-in model in
      which Cbfb-MYH11 expression was activated by Lck-Cre, there was a 10-fold
      reduction in thymocyte numbers in adult thymus, resulting mainly from impaired
      survival of CD4+CD8+ thymocytes. Although Cbfb-MYH11 derepressed CD4 expression
      efficiently in reporter assays, such derepression was less pronounced in vivo. On
      the other hand, CD4 expression was derepressed and thymocyte development was
      blocked at DN1 and DN2 stages in E17.5 Cbfb(-/GFP) thymus, with a 20-fold
      reduction of total thymocyte numbers. Our data suggest that Cbfb-MYH11 suppressed
      Cbfb in several stages of T-cell development and provide a mechanism for CBFB
      MYH11 association with myeloid but not lymphoid leukemia.

PMID- 17185463
TI  - Dasatinib induces complete hematologic and cytogenetic responses in patients with
      imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis.
AB  - The prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast
      crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can
      induce responses in a subset of these patients, resistance to the drug develops
      rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL
      and SRC family kinases. After promising phase 1 results, we report the results of
      phase 2 clinical trials of dasatinib in patients with imatinib-resistant or 
      intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up,
      dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and
      LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these
      patients, respectively. Most (86%) of these MCyRs were complete cytogenetic
      responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively,
      of MBC- and LBC-CML patients achieving MaHR had not experienced disease
      progression at the 8-month follow-up. Response rates were similar in patients
      with and without BCR-ABL mutations known to confer resistance to imatinib.
      Dasatinib was well tolerated. Nonhematologic adverse events were mild to
      moderate. Cytopenias were common and could be managed by dose modification.
      Dasatinib is highly active and produces hematologic and cytogenetic responses in
      a significant number of patients with imatinib-resistant or -intolerant MBC- and
      LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and
      #CA180015.

PMID- 17185464
TI  - Gene expression profiling and correlation with outcome in clinical trials of the
      proteasome inhibitor bortezomib.
AB  - The aims of this study were to assess the feasibility of prospective
      pharmacogenomics research in multicenter international clinical trials of
      bortezomib in multiple myeloma and to develop predictive classifiers of response
      and survival with bortezomib. Patients with relapsed myeloma enrolled in phase 2
      and phase 3 clinical trials of bortezomib and consented to genomic analyses of
      pretreatment tumor samples. Bone marrow aspirates were subject to a negative
      selection procedure to enrich for tumor cells, and these samples were used for
      gene expression profiling using DNA microarrays. Data quality and correlations
      with trial outcomes were assessed by multiple groups. Gene expression in this
      dataset was consistent with data published from a single-center study of newly
      diagnosed multiple myeloma. Response and survival classifiers were developed and
      shown to be significantly associated with outcome via testing on independent
      data. The survival classifier improved on the risk stratification provided by the
      International Staging System. Predictive models and biologic correlates of
      response show some specificity for bortezomib rather than dexamethasone.
      Informative gene expression data and genomic classifiers that predict clinical
      outcome can be derived from prospective clinical trials of new anticancer agents.

PMID- 17185465
TI  - Chromatin-modifying agents permit human hematopoietic stem cells to undergo
      multiple cell divisions while retaining their repopulating potential.
AB  - Human hematopoietic stem cells (HSCs) exposed to cytokines in vitro rapidly
      divide and lose their characteristic functional properties presumably due to the
      alteration of a genetic program that determines the properties of an HSC. We have
      attempted to reverse the silencing of this HSC genetic program by the sequential
      treatment of human cord blood CD34(+) cells with the chromatin-modifying agents,
      5-aza-2'-deoxycytidine (5azaD) and trichostatin A (TSA). We determined that all
      CD34(+)CD90(+) cells treated with 5azaD/TSA and cytokines after 9 days of
      incubation divide, but to a lesser degree than cells exposed to only cytokines.
      When CD34(+)CD90(+) cells that have undergone extensive number of cell divisions
      (5-10) in the presence of cytokines alone were transplanted into immunodeficient
      mice, donor cell chimerism was not detectable. By contrast, 5azaD/TSA-treated
      cells that have undergone similar numbers of cell divisions retained their marrow
      repopulating potential. The expression of several genes and their products
      previously implicated in HSC self-renewal were up-regulated in the cells treated
      with 5azaD/TSA as compared to cells exposed to cytokines alone. These data
      indicate that HSC treated with chromatin-modifying agents are capable of
      undergoing repeated cell divisions in vitro while retaining their marrow
      repopulating potential.

PMID- 17185466
TI  - Natural history and early diagnosis of LAD-1/variant syndrome.
AB  - The syndrome of leukocyte adhesion deficiency (LAD) combined with a severe
      Glanzmann-type bleeding disorder has been recognized as a separate disease
      entity. The variability in clinical and cell biological terms has remained
      largely unclear. We present data on 9 cases from 7 unrelated families, with 3
      patients being actively followed for more than 12 years. The disease entity,
      designated LAD-1/variant syndrome, presents early in life and consists of
      nonpussing infections from bacterial and fungal origin, as well as a severe
      bleeding tendency. This is compatible with 2 major blood cell types contributing
      to the clinical symptoms (ie, granulocytes and platelets). In granulocytes of the
      patients, we found adhesion and chemotaxis defects, as well as a defect in NADPH
      oxidase activity triggered by unopsonized zymosan. This last test can be used as
      a screening test for the syndrome. Many proteins and genes involved in adhesion
      and signaling, including small GTPases such as Rap1 and Rap2 as well as the major
      Rap activity-regulating molecules, were normally present. Moreover, Rap1
      activation was intact in patients' blood cells. Defining the primary defect
      awaits genetic linkage analysis, which may be greatly helped by a more precise
      understanding and awareness of the disease combined with the early identification
      of affected patients.

PMID- 17185467
TI  - Patients with adenosine deaminase deficiency surviving after hematopoietic stem
      cell transplantation are at high risk of CNS complications.
AB  - Adenosine deaminase (ADA) deficiency is a systemic metabolic disease that causes
      an autosomal recessive variant of severe combined immunodeficiency (SCID) and
      less consistently other complications including neurologic abnormalities.
      Hematopoietic stem cell transplantation (HSCT) is able to correct the
      immunodeficiency, whereas control of nonimmunologic complications has not been
      extensively explored. We applied HSCT in 15 ADA-deficient patients consecutively
      treated at our institutions since 1982 and analyzed long-term outcome. Seven
      patients received transplants without conditioning from HLA-matched family donors
      (MFDs); the other 8 patients received conditioning and were given transplants
      either from HLA-mismatched family donors (MMFDs; n = 6) or from matched unrelated
      donors (MUDs; n = 2). At a mean follow-up period of 12 years (range, 4-22 years),
      12 patients are alive with stable and complete immune reconstitution (7 of 7
      after MFD, 4 of 6 after MMFD, and 1 of 2 after MUD transplantation). Six of 12
      surviving patients show marked neurologic abnormalities, which include mental
      retardation, motor dysfunction, and sensorineural hearing deficit. We were unable
      to identify disease or transplantation-related factors correlating with this
      divergent neurologic outcome. The high rate of neurologic abnormalities observed
      in long-term surviving patients with ADA deficiency indicates that HSCT commonly
      fails to control CNS complications in this metabolic disease.

PMID- 17185468
TI  - Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma
      (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the
      International Lymphoma Epidemiology Consortium (InterLymph).
AB  - A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by
      the accumulating evidence of common genetic variations altering NHL risk.
      However, the pattern of NHL heritability remains poorly understood. We conducted
      a pooled analysis of 10 211 NHL cases and 11 905 controls from the International
      Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those
      with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and
      95% confidence intervals (CIs) of NHL and its subtypes were estimated from
      unconditional logistic regression models with adjustment for confounders. NHL
      risk was elevated for individuals who reported first-degree relatives with NHL
      (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% CI = 1.1-2.3), and
      leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who
      reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for
      all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL
      risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a
      first-degree relative had leukemia, NHL risk was highest among women who reported
      a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL
      heritability appeared to be uniform across NHL subtypes, but risk patterns
      differed by specific hematopoietic malignancies and the sex of the relative,
      revealing critical clues to disease etiology.

PMID- 17185470
TI  - Losing your rights: complications of misdiagnosis.

PMID- 17185471
TI  - Assessing and managing the risks in the stalking situation.
AB  - Stalking is a common social problem, often driven by psychiatric disorder in its
      perpetrators and productive of psychological and social damage in its victims.
      Assessing and managing the risks in the stalking situation is a task that
      frequently falls on the mental health professional. The concerns of risks in the
      stalking situation are not confined to violence but include psychosocial damage,
      chronicity, and recurrence, and, for the stalker, arrest and incarceration. This
      article outlines a structured approach to assessment and management involving
      domains based on the relationship between stalker and victim, the type of
      motivation driving the stalking, the stalker's risk profile, the victim's risk
      profile, and finally, the legal and mental health context. The assessment is
      closely linked to management strategies to counter specific ascertained risks and
      future hazards. These strategies will be limited, or facilitated, according to
      the current legal and mental health contexts that have a critical impact on the
      stalking situation.

PMID- 17185469
TI  - Regulation of systemic and local neutrophil responses by G-CSF during pulmonary
      Pseudomonas aeruginosa infection.
AB  - Granulocyte colony-stimulating factor (G-CSF) regulates the production,
      maturation, and function of neutrophils. Its expression is often induced during
      infection, resulting in high concentrations of G-CSF in inflammatory exudates and
      in the blood, suggesting that it may regulate both local and systemic neutrophil
      responses. Herein, we characterize the neutrophil response in G-CSFR(-/-) mice
      following intratracheal injection with Pseudomonas aeruginosa-laden agarose
      beads, modeling the pulmonary infection observed in many patients with cystic
      fibrosis. G-CSFR(-/-) mice are markedly susceptible to bronchopulmonary P
      aeruginosa infection, exhibiting decreased survival and bacterial clearance as
      well as extensive damage to lung tissue. The systemic neutrophil response was
      mediated primarily by enhanced neutrophil release from the bone marrow rather
      than increased neutrophil production and was attenuated in G-CSFR(-/-) mice.
      Despite normal to increased local production of inflammatory chemokines,
      neutrophil accumulation into the infected lung of G-CSFR(-/-) mice was markedly
      reduced. Moreover, the percentage of apoptotic neutrophils in the lung was
      elevated, suggesting that G-CSF signals may play an important role in regulating
      neutrophil survival at the inflammatory site. Collectively, these data provide
      new evidence that G-CSF signals play important but specific roles in the
      regulation of the systemic and local neutrophil response following infection.

PMID- 17185472
TI  - Commentary: The importance of professional judgment in evaluation of stalking and
      threatening situations.
AB  - When a person is stalked, a common reaction is to consult an expert for the
      answers to several key questions: Is the stalker dangerous? How can I get the
      stalker to stop the behavior? What should I do to protect myself? Although
      certain risk factors are associated with an increased likelihood of violence,
      care must be taken in using risk factors to predict violence, because there are
      many exceptions to and subtleties in such analyses. Risks in stalking situations
      depend on interactions of potentially fluctuating and interrelated factors, and
      risk assessments need to be updated as more information becomes available. The
      consultant must consider a variety of strategies to stop the stalking behavior
      and to protect the victim. When one strategy does not work, the consultant should
      recommend shifting to another strategy. Until we have long-term follow-up studies
      about the impact of each intervention on each type of stalking situation,
      assessments of stalking situations will require the use of professional judgment
      and flexibility in conjunction with knowledge of the available literature.

PMID- 17185473
TI  - Commentary: Stalking risk profile.
AB  - Paul Mullen and his colleagues have developed a Stalking Risk Profile that is the
      latest model for assessing and managing stalkers. The model includes an
      assessment of the nature of the relationship between the stalker and his victim;
      the stalker's motivations; the general psychological, psychopathological, and
      social realities of the stalker; the circumstances of the victim, and the legal
      and mental health context. The model is not an actuarial scale, but rather an
      assessment to be used on a case-by-case basis. It recommends certain standardized
      tests as part of the assessment. The Stalker Risk Profile is the most thorough
      risk assessment to date. It includes victim variables and provides specifics for
      assessment and specifics for treatment of the stalker.

PMID- 17185474
TI  - Competency to stand trial and the seriousness of the charge.
AB  - Authorities disagree as to whether and how the mental capacity required for
      competence to stand trial should change as the charges against a defendant become
      more serious. Intuition and practice in other areas of law and psychiatry suggest
      that the mental capacity required should increase in these circumstances. The
      reasons relate to our belief that serious mistakes are more to be avoided and to
      a principle of "proportionality," according to which the threshold level of
      capacity required is derived, in part, from the consequences of a person's being
      found competent. The article compares two approaches to "proportionality." The
      conclusions have implications for the wording of examiners' conclusions and for
      the criteria by which patients are regarded as "restored to competence."

PMID- 17185475
TI  - Commentary: UK perspective on competency to stand trial.
AB  - This commentary offers a perspective from another common law jurisdiction,
      specifically the law in England and Wales, where competency to stand trial on a
      criminal charge is known as fitness to plead. The commentary begins with a
      discussion on the principle of proportionality evident in health care decisions
      by way of comparison with the topic in the criminal arena. Fitness to plead is an
      historical legal concept and employs an intellectual test that has evolved very
      little since its appearance in case law. There have been amendments, through
      statute, to its procedure and outcomes following a determination of being unfit
      to plead. However, competency to stand trial in England and Wales remains a more
      marginal issue than in the United States. Recent developments in domestic and
      European jurisprudence have been related to consideration of the requirements for
      a fair trial, driven by the demands of the European Convention on Human Rights.

PMID- 17185476
TI  - Lies and coercion: why psychiatrists should not participate in police and
      intelligence interrogations.
AB  - Police interrogators routinely use deceptive techniques to obtain confessions
      from criminal suspects. The United States Executive Branch has attempted to
      justify coercive interrogation techniques in which physical or mental pain and
      suffering may be used during intelligence interrogations of persons labeled
      unlawful combatants. It may be appropriate for law enforcement, military, or
      intelligence personnel who are not physicians to use such techniques. However,
      forensic psychiatry ethical practice requires honesty, striving for objectivity,
      and respect for persons. Deceptive and coercive interrogation techniques violate
      these moral values. When a psychiatrist directly uses, works with others who use,
      or trains others to use deceptive or coercive techniques to obtain information in
      police, military, or intelligence interrogations, the psychiatrist breaches basic
      principles of ethics.

PMID- 17185477
TI  - Commentary: It's about the fundamentals.
AB  - Recent actions by the American Psychiatric Association, the American Medical
      Association, and the American Psychological Association document a growing
      consensus that health professionals should not become directly involved in
      hostile interrogations. Challenging questions remain regarding the permissibility
      of indirect involvement, such as training directed toward promoting the humanity
      of interrogation procedures and the reliability of their results. A fundamental
      challenge comes from those who hold that a physician may relinquish the caring
      role and proceed to disregard medical ethics altogether. Some experts have even
      gone so far as to allege that all existing rules of medical ethics are baseless
      statements and thus cannot bind anyone. Forensic psychiatrists' continuing
      contributions to this debate are critical.

PMID- 17185478
TI  - A pilot Rasch scaling of lawyers' perceptions of expert bias.
AB  - How seriously do attorneys consider the biases of their retained mental health
      experts? Participants in this pilot study included 40 attorneys, randomly
      selected from a pool of members of the Pennsylvania Bar Institute, who rated-for
      their biasing potential-several situations that might affect the behavior of an
      expert. A Rasch analysis produced a linear scale as to the perceived biasing
      potential of these different items from most to least biasing. Among other
      results, the study suggests that attorneys do view mental health experts who work
      on both sides of cases as being more balanced in their testimony. However, they
      also indicated that they have a preference for using individuals who repeatedly
      testify for one side. Working for only one side in both civil and criminal cases
      yielded large scaled values. Additional comments offered by respondents indicated
      that: (1) an opposing expert also serving as the litigant's treater and (2) an
      opposing expert being viewed as a "hired gun" (supplying an opinion only for
      money) were viewed by subjects as not being very biased. A discussion of the
      results raises the need for future research in this area.

PMID- 17185479
TI  - Lawyers' attitudes toward involuntary treatment.
AB  - This study examined whether lawyers' attributions of responsibility for mental
      illnesses affect their decisions about involuntary treatment. A survey that was
      mailed in 2003 to Illinois lawyers involved in involuntary commitment elicited
      recommendations for involuntary treatment for characters presented in vignettes.
      The survey also sought respondents' attributions of personal responsibility for
      the onset and recurrence of mental illnesses. A total of 89 lawyers responded to
      the survey, a response rate of 48 percent. Decisions to hospitalize persons with
      mental illness involuntarily increased significantly with the level of risk of
      harm and were significantly related to attributions of responsibility for the
      recurrence of mental illness. Decisions to recommend involuntary medication were
      not related to attributions of responsibility.

PMID- 17185480
TI  - Competency for creation, use, and revocation of psychiatric advance directives.
AB  - Psychiatric advance directives help promote patient involvement in treatment and
      expedite psychiatric care. However, clinicians are unsure of how to use
      directives, partly due to poor clarity regarding standards for capacity to
      create, use, and revoke them. This article recommends possible capacity
      standards. Capacity to create directives is a legal presumption, supported by
      empirical data. Standards are discussed for the subset of cases in which capacity
      assessment is needed. Use of directives may be triggered by incapacity to provide
      informed consent to treatment, although tailored, individualized points of
      activation may also be considered. In many states, revocation of a psychiatric
      advance directive requires adequate decision-making capacity. Setting a capacity
      standard for revocation presents challenges, however, in light of obstacles to
      providing treatment when revocation is attempted and the fact that many patients
      prefer revocable directives. As more directives are created and used, additional
      research and statutory refinements are warranted.

PMID- 17185481
TI  - Shared psychotic disorder and criminal responsibility: a review and case report
      of folie a trois.
AB  - We present a case of shared psychotic disorder involving three sisters who were
      successful in establishing an insanity defense on numerous felony charges in the
      South Carolina criminal court system. Two of the authors of this article were
      court-appointed examiners in this case. We then present a history of shared
      psychotic disorder, an overview of the use of this diagnosis in the defense of
      insanity, and a discussion of the disposition of individuals with "temporary
      insanity." Finally, we compare shared psychotic disorder, culturally based belief
      systems, and religious cults, with a focus on their common and contrasting
      characteristics.

PMID- 17185482
TI  - Attorneys' requests for complete tax records from opposing expert witnesses: some
      approaches to the problem.
AB  - As part of an impeachment attempt on cross-examination of opposing expert
      witnesses in trial or deposition, the cross-examining attorney may request the
      complete tax records of the expert. It is widely believed that expert witnesses
      may be expected to express opinions that favor the parties who engage them and
      who pay their fees. Theoretically, the purpose of this request is an attempt to
      paint the expert as a "hired gun" whose major source of income is forensic work.
      The different issues, statutes, and case law citations that bear on requests for
      tax records are reviewed, and the strategies for coping with this tactic are
      suggested.

PMID- 17185483
TI  - Back to the past in California: a temporary retreat to a Tarasoff duty to warn.
AB  - The original Tarasoff decision created a duty for California psychotherapists to
      warn potential victims of their patients. After rehearing the matter two years
      later, the California Supreme Court, in the landmark second Tarasoff decision,
      changed the duty to warn to a duty to protect potential victims, with warning as
      only one of the options for discharging that duty. Despite this change, the
      Tarasoff duty frequently was referred to erroneously as a duty to warn. This
      misunderstanding and an ambiguous California immunity statute culminated in
      "simplified" jury instructions and two appellate court decisions in 2004 in which
      it was assumed without question that there was a duty to warn, with liability for
      not doing so regardless of rationale. As a result of persistent lobbying by the
      California Psychiatric Association and other mental health groups, a recent bill
      corrected the problem created by the courts, returning the Tarasoff duty to a
      duty to protect.

PMID- 17185485
TI  - Civil commitment is disappearing in Oregon.
AB  - Over the past 20 years, in Oregon, the number of individuals entered into the
      civil commitment process has risen, but the number of those actually committed
      has gone down dramatically. This commentary compares commitment data during a
      time when the state's population has increased substantially, while commitment
      rates have dropped by 50 percent. There are many possible factors that have
      contributed to this decline in commitment rates, including a stricter functional
      definition of "danger to self or others," but perhaps the most significant reason
      is the shortage of the acute psychiatric beds that are essential in the
      commitment process. It is hard not to conclude that civil commitment in this
      state is headed toward functional extinction.

PMID- 17185484
TI  - Fratricide: a forensic psychiatric perspective.
AB  - Analyses of fratricide rates based on national homicide data have provided some
      general information pertaining to offenders and victims of sibling homicide but
      are limited by data constraints to examining a few major variables. Exploring
      fratricide from a forensic psychiatric perspective could uncover other related
      factors and provide insight into why some individuals murder their siblings. In a
      retrospective study of data from coroners' files on domestic homicide pertaining
      to individuals killed by their siblings over a 10-year period in Quebec, Canada,
      we identified several specific offender and victim characteristics and
      circumstances surrounding offenses. The impact of mental illness and substance
      abuse on fratricidal behavior is indicated, underscoring the importance of
      identifying existing psychopathology. From a forensic psychiatric perspective, we
      identify characteristic patterns and discuss potential dynamics operating in
      fratricide. We raise some issues relevant to treatment and prevention, including
      the fact that most cases are alcohol-related, impulsive, and unpredictable until
      the moment they occur.

PMID- 17185486
TI  - Update on the disposition of military insanity acquittees.
AB  - There has been little study of the use of the insanity defense within the
      military judicial system, and aggregated data concerning such cases are not
      readily available when needed. Useful information is not consolidated in a
      central location, hindering potential research and the development of systemic
      improvements. One key area that would benefit from closer analysis is the process
      of the disposition of insanity acquittees. The Manual for Courts-Martial (2000
      ed. Washington, DC: U.S. Government Printing Office) provides limited guidance in
      procedures to disposition, outlining the process in rather broad terms. The
      result is often a time-consuming and resource-draining process that can create
      significant burdens for both the military legal and health care systems. The need
      to address challenges within the system is discussed, and the creation of a
      centralized databank as a step toward improving this system is recommended.

PMID- 17185488
TI  - An expert who listened to a telephonic deposition without announcing his
      presence.

PMID- 17185487
TI  - Clark v. Arizona: diminishing the right of mentally ill individuals to a full and
      fair defense.
AB  - In Clark v. Arizona, the U.S. Supreme Court was faced with two main questions:
      Does Arizona's insanity defense statute, with its abridged M'Naughten standard,
      violate the Fourteenth Amendment? And does Arizona case law, with its complete
      prohibition on the use of mental disease or defect evidence to combat required
      mens rea elements of a crime, violate due process? In a six-three decision, the
      Court answered both of these questions in the negative.

PMID- 17185489
TI  - Mental health care in juvenile detention facilities: a review.

PMID- 17185490
TI  - Psychiatric advance directives.

PMID- 17185491
TI  - Inactivity and fat cell hyperplasia: fat chance?

PMID- 17185492
TI  - Ventilatory muscle activation and inflammation: cytokines, reactive oxygen
      species, and nitric oxide.
AB  - Strenuous diaphragmatic contractions that are induced by inspiratory resistive
      breathing initiate an inflammatory response that involves the elevation of pro-
      and anti-inflammatory cytokines within the diaphragm, which may then spill into
      the circulation. The production of reactive oxygen species within working
      respiratory muscles increases in response to these strenuous diaphragmatic
      contractions. At the same time, diaphragmatic nitric oxide (NO) production
      declines significantly, despite a time-dependent increase in NO synthase isoform
      protein expression. The increase in adhesion molecule expression and infiltration
      of granulocytes and macrophages that follows may contribute to the contraction
      induced diaphragm injury. Enhanced generation of reactive oxygen species,
      oxidative stress augmentation, reduced NO production, and glycogen depletion are
      potential stimuli for the cytokine induction that is secondary to strenuous
      diaphragmatic contractions. This production of cytokines within the diaphragm may
      contribute to the diaphragmatic muscle fiber injury that occurs with strenuous
      contractions or to the expected repair process. TNF-alpha is a cytokine that
      compromises diaphragmatic contractility and may contribute to muscle wasting. IL
      6 is a cytokine that may have beneficial systemic effects by mobilizing glucose
      from the liver and free fatty acids from the adipose tissue and providing them to
      the strenuously working respiratory muscles. Thus cytokine upregulation within
      the working diaphragm may be adaptive and maladaptive.

PMID- 17185493
TI  - Optimal electrode placement for noninvasive electrical stimulation of human
      abdominal muscles.
AB  - Abdominal muscles are the most important expiratory muscles for coughing. Spinal
      cord-injured patients have respiratory complications because of abdominal muscle
      weakness and paralysis and impaired ability to cough. We aimed to determine the
      optimal positioning of stimulating electrodes on the trunk for the noninvasive
      electrical activation of the abdominal muscles. In six healthy subjects, we
      compared twitch pressures produced by a single electrical pulse through surface
      electrodes placed either posterolaterally or anteriorly on the trunk with twitch
      pressures produced by magnetic stimulation of nerve roots at the T(10) level. A
      gastroesophageal catheter measured gastric pressure (Pga) and esophageal pressure
      (Pes). Twitches were recorded at increasing stimulus intensities at functional
      residual capacity (FRC) in the seated posture. The maximal intensity used was
      also delivered at total lung capacity (TLC). At FRC, twitch pressures were
      greatest with electrical stimulation posterolaterally and magnetic stimulation at
      T(10) and smallest at the anterior site (Pga, 30 +/- 3 and 33 +/- 6 cm H(2)O vs.
      12 +/- 3 cm H(2)O; Pes 8 +/- 2 and 11 +/- 3 cm H(2)O vs. 5 +/- 1 cm H(2)O; means
      +/- SE). At TLC, twitch pressures were larger. The values for posterolateral
      electrical stimulation were comparable to those evoked by thoracic magnetic
      stimulation. The posterolateral stimulation site is the optimal site for
      generating gastric and esophageal twitch pressures with electrical stimulation.

PMID- 17185494
TI  - Increased insulin-stimulated Akt pSer473 and cytosolic SHP2 protein abundance in
      human skeletal muscle following acute exercise and short-term training.
AB  - The purpose of the present study was to determine in human skeletal muscle
      whether a single exercise bout and 7 days of consecutive endurance (cycling)
      training 1) increased insulin-stimulated Akt pSer(473) and 2) altered the
      abundance of the protein tyrosine phosphatases (PTPases), PTP1B and SHP2. In
      healthy, untrained men (n = 8; 24 +/- 1 yr), glucose infusion rate during a
      hyperinsulinemic euglycemic clamp, when compared with untrained values, was not
      improved 24 h following a single 60-min bout of endurance cycling but was
      significantly increased ( approximately 30%; P < 0.05) 24 h following completion
      of 7 days of exercise training. Insulin-stimulated Akt pSer(473) was
      approximately 50% higher (P < 0.05) 24 h following the acute bout of exercise,
      with this effect remaining after 7 days of training (P < 0.05). Insulin
      stimulated insulin receptor and insulin receptor substrate-1 tyrosine
      phosphorylation were not altered 24 h after acute exercise and short-term
      training. Insulin did not acutely regulate the localization of the PTPases, PTP1B
      or SHP2, although cytosolic protein abundance of SHP2 was increased (P < 0.05;
      main effect) 24 h following acute exercise and short-term training. In
      conclusion, insulin-sensitive Akt pSer(473) and cytosolic SHP2 protein abundance
      are higher after acute exercise and short-term training, and this effect appears
      largely due to the residual effects of the last bout of prior exercise. The
      significance of exercise-induced alterations in cytosolic SHP2 and insulin
      stimulated Akt pSer(473) on the improvement in insulin sensitivity requires
      further elucidation.

PMID- 17185495
TI  - Doping dose of salbutamol and exercise: deleterious effect on cancellous and
      cortical bones in adult rats.
AB  - Animal studies suggest that bone remodeling is under beta-adrenergic control via
      the sympathetic nervous system. To our knowledge, the impact of beta-agonist
      substances, at doping doses, has not been studied in adult rats. The purpose of
      this study was to examine the effects of salbutamol injections with or without
      treadmill exercise on trabecular and cortical bone in adult rats. Adult (36 wk of
      age) female Wistar rats (n = 56) were treated with salbutamol (3 mg.kg(-1).day(
      1) sc, 5 days/wk) or vehicle (sham) with or without subsequent treadmill exercise
      (13 m/min, 60 min/day, 5 days/wk) for 10 wk. Tibial and femoral bone mineral
      density was analyzed by dual-energy X-ray absorptiometry. Metaphysic trabecular
      bone structure was analyzed by micro-CT at the time of the animals' death. Bone
      cell activities were assessed histomorphometrically. After 10 wk, the increase in
      bone mineral density was less in salbutamol-treated than in sham rats (+3.3% vs.
      +12.4%, P < 0.05), and trabecular parameters were altered and bone resorption was
      increased in salbutamol-treated rats compared with controls. The negative effect
      on bone architecture in salbutamol-treated rats persisted, even with treadmill
      exercise. These results confirm the deleterious effect of beta(2)-agonists on
      bone mass during chronic treatment and describe its effects on bone mechanical
      properties in adult rats. Bone loss occurred independently of a salbutamol
      induced anabolic effect on muscle mass and was equally severe in sedentary and
      exercising rats, despite a beneficial effect of exercise on the extrinsic and
      intrinsic energy to ultimate strain. These bone effects may have important
      consequences in athletes who use salbutamol as a doping substance.

PMID- 17185496
TI  - Contraction-relaxation coupling mechanism characterization in the thermodynamic
      phase plane: normal vs. impaired left ventricular ejection fraction.
AB  - Using simultaneous pressure-volume measurements obtained during cardiac
      catheterization, we employ the thermodynamic phase-plane (TPP) method to
      characterize global contraction-relaxation coupling (CRC) between normal and
      impaired left ventricular (LV) ejection fraction (LVEF) groups. The cardiac cycle
      inscribes a closed loop in the TPP defined by the coordinates "potential" power
      [V(dP/dt), ergs/s] and "kinetic" power [P(dV/dt), ergs/s]. The TPP-derived
      indexes kappa and rho define the chamber's contractile and CRC attributes,
      respectively. Data from 33 subjects dichotomized as normal control (n = 22, >50%
      LVEF) and impaired LVEF (n = 11, <50% LVEF) were analyzed. The results were as
      follows: kappa = 3.0 +/- 1.1 and rho = -0.38 +/- 0.21 for controls and kappa =
      5.4 +/- 1.6 and rho = -1.14 +/- 0.47 for the impaired LVEF group; kappa and rho
      are significantly higher for impaired LVEF than for control (P < 0.001 for both).
      As kappa increased, rho decreased (r = -0.69) for all subjects. Hence, ventricles
      with impaired LVEF are thermodynamically less efficient because they require more
      potential power per unit of delivered kinetic power than controls. We conclude
      that TPP-derived indexes of CRC facilitate assessment of chamber efficiency in
      thermodynamic terms and elucidate the dominant differentiating features in terms
      of CRC indexes.

PMID- 17185497
TI  - Neonatal maternal separation induces sex-specific augmentation of the hypercapnic
      ventilatory response in awake rat.
AB  - Neonatal maternal separation (NMS) is a form of stress that exerts persistent,
      sex-specific effects on the hypoxic ventilatory response. Adult male rats
      previously subjected to NMS show a 25% increase in the response, whereas NMS
      females show a response 30% lower than controls (8). To assess the extent to
      which NMS affects ventilatory control development, we tested the hypothesis that
      NMS alters the ventilatory response to hypercapnia in awake, unrestrained rats.
      Pups subjected to NMS were placed in a temperature- and humidity-controlled
      incubator 3 h/day for 10 consecutive days (P3 to P12). Control pups were
      undisturbed. At adulthood (8 to 10 wk old), rats were placed in a plethysmography
      chamber for measurement of ventilatory parameters under baseline and hypercapnic
      conditions (inspired CO(2) fraction = 0.05). After 20 min of hypercapnia, the
      minute ventilation response measured in NMS males was 47% less than controls,
      owing to a lower tidal volume response (22%). Conversely, females previously
      subjected to NMS showed minute ventilation and tidal volume responses 63 and 18%
      larger than controls respectively. Although a lower baseline minute ventilation
      contributes to this effect, the higher minute ventilation/CO(2) production
      response observed in NMS females suggests a greater responsiveness to CO(2)/H(+)
      in this group. We conclude that NMS exerts sex-specific effects on the
      hypercapnic ventilatory response and that the neural mechanisms affected by NMS
      likely differ from those involved in the hypoxic chemoreflex.

PMID- 17185498
TI  - Swallowing function and upper airway sensation in obstructive sleep apnea.
AB  - The objective of this study was to determine whether impaired upper airway (UA)
      mucosal sensation contributes to altered swallowing function in obstructive sleep
      apnea (OSA). We determined UA two-point discrimination threshold (2PDT) and
      vibratory sensation threshold (VST) in 15 men with untreated OSA and 9 nonapneic
      controls (CL). We then assessed swallowing responses to oropharyngeal fluid
      boluses delivered via a catheter. The threshold volume required to provoke
      swallowing and the mean latency to swallowing were determined, as was the phase
      of the respiratory cycle in which swallowing occurred [expressed as percentage of
      control cycle duration (%CCD)] and the extent of prolongation of the respiratory
      cycle after swallowing [inspiratory suppression time (IST)]. 2PDT and VST were
      significantly impaired in OSA patients compared with CL subjects. 2PDT was
      positively correlated with swallowing latency and threshold volume in CL
      subjects, but not in OSA patients. Threshold volume did not differ between the
      groups [median value = 0.1 ml (95% confidence interval = 0.1-0.2) for OSA and
      0.15 ml (95% confidence interval = 0.1-0.16) for CL], whereas swallowing latency
      was shorter for OSA patients [3.3 (SD 0.7) vs. 3.9 (SD 0.8) s, P = 0.04]. %CCD
      and IST were similar for OSA patients and CL subjects. However, among OSA
      patients there was a significant inverse relation between VST and IST. These
      findings suggest that oropharyngeal sensory impairment in OSA is associated with
      an attenuation of inhibitory modulating inputs to reflex and central control of
      UA swallowing function.

PMID- 17185499
TI  - Gastrocnemius muscle fascicle behavior during stair negotiation in humans.
AB  - The aim of the present study was to establish the behavior of human medial
      gastrocnemius (GM) muscle fascicles during stair negotiation. Ten healthy male
      subjects performed normal stair ascent and descent at their own comfortable speed
      on a standard-dimension four-step staircase with embedded force platforms in each
      step. Kinematic, kinetic, and electromyographic data of the lower limbs were
      collected. Real-time ultrasound scanning was used to determine GM muscle fascicle
      length changes. Musculotendon complex (MTC) length changes were estimated from
      ankle and knee joint kinematics. The GM muscle was mainly active during the push
      off phase in stair ascent, and the muscle fascicles contracted nearly
      isometrically. The GM muscle was mainly active during the touch-down phase of
      stair descent where the MTC was lengthened; however, the GM muscle fascicles
      shortened by approximately 7 mm. These findings show that the behavior and
      function of GM muscle fascicles in stair negotiation is different from that
      expected on the basis of length changes of the MTC as derived from joint
      kinematics.

PMID- 17185500
TI  - Baroreflex sensitivity, blood pressure buffering, and resonance: what are the
      links? Computer simulation of healthy subjects and heart failure patients.
AB  - The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations,
      mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an
      important characteristic of baroreflex control, is often noninvasively assessed
      by relating heart rate (HR) fluctuations to BP fluctuations; more specifically,
      spectral BRS assessment techniques focus on the BP-to-HR transfer function around
      0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated
      BP buffering is based on two considerations: 1) baroreflex-modulated peripheral
      vasomotor function is not necessarily related to baroreflex-HR transfer; and 2)
      although BP fluctuations around 0.1 Hz (Mayer waves) might be related to
      baroreflex BP buffering, they are merely a not-intended side effect of a closed
      loop control system. To further investigate the relationship between BRS and
      baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP
      control to simulate normal subjects and heart failure patients. Output variables
      for various randomly chosen combinations of feedback gains in the baroreflex arms
      were BP resonance, BP-buffering capacity, and BRS. Our results show that BP
      buffering and BP resonance are related expressions of baroreflex BP control and
      depend strongly on the sympathetic gain to the peripheral resistance. BRS is
      almost uniquely determined by the vagal baroreflex gain to the sinus node. In
      conclusion, BP buffering and BRS are unrelated unless coupled gains in all
      baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most
      likely to be attributed to vagal effects on the heart instead of to effective BP
      buffering.

PMID- 17185501
TI  - Gene expression profiling toward understanding of ALS pathogenesis.
AB  - Although more than 130 years have gone by since the first description in 1869 by
      Jean-Martin Charcot, the mechanism underlying the characteristic selective motor
      neuron degeneration in amyotrophic lateral sclerosis (ALS) has remained elusive.
      Modest advances in this research field have been achieved by the identification
      of copper/zinc superoxide dismutase 1 (SOD1) as one of the causative genes for
      rare familial ALS (FALS) and by the development and analysis of mutant SOD1
      transgenic mouse models. However, in sporadic ALS (SALS) with many more patients,
      causative or critical genes situated upstream of the disease pathway have not yet
      been elucidated and no available disease models have been established. To
      approach genes causative or critical for ALS, gene expression profiling in
      tissues primarily affected by the disease has represented an attractive research
      strategy. We have been working on screening these genes employing and combining
      several new technologies such as cDNA microarray, molecular indexing, and laser
      capture microdissection. Many of the resultant genes are of intense interest and
      may provide a powerful tool for determining the molecular mechanisms of ALS.
      However, we have barely arrived at the starting point and are confronting an
      enormous number of genes whose roles remain undetermined. Challenging tasks lie
      ahead of us such as identifying which genes are really causative for ALS and
      developing a disease model of SALS with due consideration for the expression
      changes in those genes.

PMID- 17185502
TI  - Role of polyunsaturated fatty acids for misfolding protein aggregations:
      implication for neurodegenerative diseases.
AB  - Numerous neurodegenerative diseases are accompanied by highly insoluble
      inclusions of protein aggregates within characteristic neuronal populations.
      Recent in vitro studies have advanced new aspects of protein aggregates and their
      cytotoxicity. Aggregations of unfolded proteins escape the cellular quality
      control system, such as chaperone and proteasome, which is a common feature of
      aggregates-associated neurodegeneration. Based on this idea, several factors may
      provide protein aggregates-favoring conditions that are closely involved in
      progression of diseases. In particular, we focused on polyunsaturated fatty acids
      as an important modulator for unfolded protein-aggregation in relation to disease
      pathogenesis.

PMID- 17185503
TI  - Alleviating neurodegeneration by an anticancer agent: an Hsp90 inhibitor (17
      AAG).
AB  - Heat shock proteins (HSPs) that function mainly as molecular chaperones play an
      important role in the folding and quality control of proteins. Compared with
      these chaperones, Hsp90 is unique in that it binds to substrate proteins, called
      Hsp90 client proteins. Hsp90 is involved in the folding, activation, and assembly
      of its client proteins in association with its co-chaperones. Because numerous
      oncoproteins belonging to the Hsp90 client protein family are selectively
      degraded by Hsp90 inhibitors, 17-allylamino-17-demethoxygeldanamycin (17-AAG), a
      first-in-class Hsp90 inhibitor, is now under clinical trials as a novel molecular
      targeted agent for a wide range of malignancies. In spinal and bulbar muscular
      atrophy (SBMA), the pathogenic gene product is polyglutamine (polyQ)-expanded
      androgen receptor (AR), which belongs to the Hsp90 client protein family and is
      known to be degraded by 17-AAG. We have recently demonstrated that administration
      of an anticancer agent 17-AAG significantly ameliorated polyQ-mediated motor
      neuron degeneration by reducing the total amount of mutant AR. The ability of 17
      AAG to degrade mutant protein would be directly applicable to SBMA and other
      neurodegenerative diseases in which the disease-causing proteins also belong to
      the Hsp90 client protein family. Our proposed therapeutic approach using a novel
      anticancer agent 17-AAG has emerged as a candidate for molecular-targeted
      therapies for neurodegenerative diseases.

PMID- 17185504
TI  - LRP in amyloid-beta production and metabolism.
AB  - Amyloid-beta peptide (Abeta) production and accumulation in the brain is a
      central event in the pathogenesis of Alzheimer's disease (AD). Recent studies
      have shown that apolipoprotein E (apoE) receptors, members of the low-density
      lipoprotein receptor (LDLR) family, modulate Abeta production as well as Abeta
      cellular uptake. Abeta is derived from proteolytic processing of the amyloid
      precursor protein (APP), which interacts with several members of the LDLR family.
      Studies from our laboratory have focused on two members of the LDLR family, the
      LDLR-related protein (LRP) and LRP1B. Our in vitro studies have shown that while
      LRP's rapid endocytosis facilitates APP endocytic trafficking and processing to
      Abeta, LRP1B's slow endocytosis inhibits these processes. In addition to
      modulating APP endocytic trafficking, LRP's rapid endocytosis also facilitates
      Abeta cellular uptake by binding to Abeta either directly or via LRP ligands such
      as apoE. Our in vivo studies using transgenic mice have shown that overexpression
      of LRP in central nervous system (CNS) neurons increases soluble brain Abeta and
      this increase correlates with deficits in memory. Together our studies
      demonstrate that members of the LDLR family modulate APP processing and Abeta
      metabolism by several independent mechanisms. Understanding the pathways that
      modulate brain Abeta metabolism may enable the rational design of molecular
      medicine to treat AD.

PMID- 17185505
TI  - Neuronal differentiation is accompanied by increased levels of SNAP-25 protein in
      fetal rat primary cortical neurons: implications in neuronal plasticity and
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is accompanied by progressive memory loss and decline in
      general cognitive abilities. Neuropathological hallmarks include amyloid plaque
      formation, neurofibrillary tangles, and neuronal and synaptic loss. To improve
      research models in AD, we have characterized several aspects of the primary rat
      neuronal cell culture model, which relate directly to the study of
      neuroexocytosis, neuronal plasticity, and amyloidosis. We have attempted to
      isolate and assess the neuronal enrichment of a primary cortical cell culture by
      morphological and molecular techniques, following progress of these cultured
      cells for up to 18 days in culture to identify the optimum timeframe for the
      manipulation and data collection in these cells. We observed maximum neuronal
      differentiation around day 15, which was in decline by day 18, thus, the critical
      window for manipulations in these cultures seems to be between days 12-15. The
      substantial increase in neuritic length and density was apparent at very early
      time points and peaked at day 15. In parallel to morphological assessments, we
      measured levels of a group of selected neuronally important proteins, including
      cytoskeletal and synaptic proteins. Change in the levels of cell-associated APP
      and synaptophysin were not as dramatic as that of SNAP-25 or secreted APP.
      Notably, this increased differentiation is accompanied by a dramatic increase in
      levels of SNAP-25 protein, which peaked at day 15 and declined thereafter. These
      results suggest that this neuronal population contains quantifiable presynaptic
      terminals. Thus, the establishment and molecular characterization of this
      neuronal model would have many implications in neuroscience research including
      synaptic differentiation and neuronal plasticity and for the evaluation of
      pharmacological interventions in the disease process.

PMID- 17185506
TI  - Myosin Va mutation in rats is an animal model for the human hereditary
      neurological disease, Griscelli syndrome type 1.
AB  - A spontaneous neurological mutation, dilute-opisthotonus (dop), was discovered in
      our breeding colony of Wistar rats. We found that the mutation affected the gene
      encoding Myosin Va (MyoVA), an actin-based molecular motor. Analysis of the
      myosin Va (Myo5a) gene of the dop genome showed the presence of a complex
      rearrangement consisting of a 306-bp inversion associated with 217-bp and 17-bp
      deletions. A 141-bp exon is skipped in the dop transcript, producing a dop cDNA
      with a 141 in-frame deletion in the sequences encoding the head region.
      Expression of the MyoVA protein is severely impaired in the brains of dop
      homozygous rats, suggesting they have a null mutation for Myo5a. In a
      morphological analysis of the cerebella of dop rats, we found an absence of
      smooth endoplasmic reticulum (SER) and of inositol 1,4,5-triphosphate (IP3)
      receptors in the dendritic spines of Purkinje cells (PC). The SER acts as an
      intracellular Ca(2+) store and IP3-mediated Ca(2+) signaling in dendritic spines
      plays a critical role in synaptic regulation. We therefore measured synaptic
      transmission and long-term depression (LTD), a form of synaptic plasticity
      underlying cerebellar motor learning, at PC synapses in the cerebella of dop
      rats. We found that synaptic transmission at the PC synapses is largely normal,
      whereas the LTD is deficient due to a decrease in IP3-mediated Ca(2+) release
      from the SER in the PC spines of the dop cerebella. These findings may account
      for the ataxic movements and clonic convulsions displayed by dop rats. They also
      contribute to our understanding of the neurological disease mechanisms of the
      human hereditary disease Griscelli syndrome type 1, which is caused by mutation
      of the Myo5a gene.

PMID- 17185507
TI  - Brain keratan sulfate and glial scar formation.
AB  - In response to injury to the central nervous system (CNS), reactive astrocytes
      appear and accumulate in the wounded area, leading to glial scar formation. Glial
      scar is the physical barrier to axonal regeneration of injured neurons.
      Chondroitin sulfate proteoglycans are inhibitory to axon outgrowth and are
      upregulated in reactive astrocytes upon CNS injury. It is known that keratan
      sulfate proteoglycans (KSPGs) are also augmented after CNS injury and act as
      inhibitory cues. We give a brief overview of CNS injury and cover our recent data
      regarding the relationship between glial scar formation and KS. KS expression in
      the developing brain is detectable with 5D4, a KS-specific monoclonal antibody.
      These 5D4 immunoreactivities are eliminated in mice deficient in N
      acetylglucosamine 6-O-sulfotransferase-1. In adult mice, brain injury apparently
      upregulates mRNA expression of N-acetylglucosamine 6-O-sulfotransferase-1 as well
      as 5D4-reactive KS in the wounded area. Intriguingly, the expression of 5D4
      reactive KS and reactive astrocyte accumulation in the wounded area are
      dramatically diminished in the sulfotransferase-deficient mice. Consequently, the
      deficient mice exhibit a marked reduction in scar formation and enhancement of
      neuronal regeneration after brain injury. Thus, N-acetylglucosamine 6-O
      sulfotransferase-1 plays indispensable roles in brain KS biosynthesis and glial
      scar formation after brain injury.

PMID- 17185508
TI  - The direct and indirect effects of serofendic acid on neuroprotection.
AB  - Serofendic acid is a novel neuroprotective factor isolated from fetal calf serum.
      To elucidate the mechanisms how serofendic acid exerts neuroprotection, we
      examined its effects on glutamate-induced excito-toxicity in mouse cortical
      neurons. The effects of serofendic acid on inflammatory cytokine and neurotrophin
      production by glial cells were also examined to evaluate the indirect
      neuroprotection. Serofendic acid significantly and dose dependently increased
      survival of mouse cortical neurons after 10 muM N-methyl-D-asparate (NMDA)
      exposure. However, it did not affect production of inflammatory cytokines and
      neurotrophins by microglia as assessed by reverse transciption polymerase chain
      reaction (RT-PCR) for mRNA expression and ELISA for protein levels, though it
      suppressed tumor necrosis factor (TNF)-alpha production by astrocytes. Thus,
      serofendic acid works directly on neurons to protect against glutamate toxicity.
      Suppression of TNF-alpha production by astoryctes may also synergistically exert
      neuroprotective functions of serofendic acid. Serofendic acid may be of use for
      the future therapeutic strategy against ischemic and degenerative neurological
      disorders.

PMID- 17185509
TI  - Cytoplasmic lipid droplets: rediscovery of an old structure as a unique platform.
AB  - Cytoplasmic lipid droplets (LDs) exist in virtually any kind of cell. They have a
      core of lipid esters covered by the surface phospholipid monolayer. A number of
      proteins related to various cell functions are present in LDs and/or LD-rich
      subcellular fractions, suggesting that LDs are an independent organelle that is
      engaged in various cellular activities. Furthermore, a recent study suggested
      that LDs are a platform where the proteasomal and autophagic pathways converge.
      The molecular composition and architecture of LDs are discussed here, with
      special reference to the technical difficulties encountered when analyzing this
      unique organelle.

PMID- 17185510
TI  - Molecular mechanisms of axon specification and neuronal disorders.
AB  - A cardinal feature of neurons is the morphological polarity of neurons with
      serious functional implications. Typically, a neuron has a single axon and
      several dendrites. Neuronal polarity is essential for the unidirectional signal
      flow from somata or dendrites to axons in neurons. The initial event in
      establishing a polarized neuron is the specification of a single axon. Although
      researchers are accumulating a catalog of structural, molecular, and functional
      differences between axons and dendrites, we are only now beginning to understand
      the molecular mechanisms involved in the establishment of neuronal polarity. We
      have described recent advances in the understanding of cellular events in the
      early development of an axon and dendrites. Several groups, including ours,
      reported that the phosphatidylinositol 3-kinase (PI3-kinase)/Akt (also called
      protein kinase B)/glycogen synthase kinase-3beta (GSK-3beta)/collapsin response
      mediator protein-2 (CRMP-2) pathway is important for axon specification and
      elongation. Recent studies have revealed the roles that Rho family small GTPases,
      the Par complex, and cytoskeleton-related proteins play in the initial events of
      neuronal polarization downstream of PI3-kinase. We discuss the roles of polarity
      regulating molecules and the potential mechanisms underlying the specification of
      an axon and dendrites. Polarity-regulating molecules participate in various
      neuronal disorders. In this review, the signal transduction of GSK-3beta and CRMP
      2 is introduced as a new target for the treatment of Alzheimer's disease (AD) and
      nerve injury. These findings may help clarify causes of and treatments aimed at
      reversing AD and nerve injury.

PMID- 17185511
TI  - Disrupted-in-schizophrenia-1 (DISC1): a key susceptibility factor for major
      mental illnesses.
AB  - Here we overview Disrupted-in-Schizophrenia-1 (DISC1), a promising lead in
      studying the pathophysiology of major mental conditions. Genetic association
      studies reproducibly suggest involvement of DISC1 in both schizophrenia and
      bipolar disorder in several ethnic groups. Different from several other
      susceptibility genes for schizophrenia, such as neuregulin-1 and dysbindin, there
      are two independent pedigrees in which genetic variations of DISC1 directly
      segregate with major mental conditions. This uniqueness has facilitated
      neurobiology of DISC1, which may hopefully lead to an important breakthrough in
      understanding of pathophysiology of major mental conditions. DISC1 is a
      multifunctional protein that plays a role in neurodevelopment and cell signaling.
      In autopsied brains from patients with psychosis and substance abuse, change in
      subcellular distribution of DISC1 is observed. DISC1 interacts with
      phosphodiesterase (PDE) 4B that degrades cyclic AMP (cAMP), which may be a
      regulatory molecule for working memory in the prefrontal cortex. Knockdown
      expression of DISC1 in developing cerebral cortex in mouse brains leads to
      changes that resemble, at least in part, the pathology found in patients with
      schizophrenia. These results support involvement of DISC1 in the pathophysiology
      of major mental conditions, including schizophrenia, in several mechanisms.

PMID- 17185512
TI  - Psychological, neuroimaging, and biochemical studies on functional association
      between impulsive behavior and the 5-HT2A receptor gene polymorphism in humans.
AB  - It has been suggested that impulsive behavior is caused by dysfunctional
      serotonergic 5-HT neurotransmission in the central nervous system (CNS). Brain
      neuroimaging studies have shown that behavioral inhibition is linked to the
      activation of cortex sites such as the ventral frontal cortex. Positron emission
      tomography (PET) imaging with [(18)F]altanserin to characterize 5-HT(2A) receptor
      binding revealed a reduction in 5-HT(2A) binding in the ventral frontal cortex in
      women who had recovered from impulsive diseases. These clinical, neuroimaging,
      and pharmacological studies appear to support the hypothesis that functional
      alteration of neurotransmission due to genetic polymorphisms of the 5-HT
      receptors may be involved in impulsive behavior modulation. Following evaluation
      by a self-reporting measure, it was proposed that a polymorphism in the promoter
      of the 5-HT(2A) receptor gene is the underlying cause of impulsive behavior;
      however, this hypothesis is not convincing. We examined whether the polymorphism
      in the 5-HT(2A) receptor gene promoter is involved in impulsive aggression by
      evaluating a behavioral task (Go/No-go task) in normal volunteers. The
      polymorphism of the 5-HT(2A) receptor gene promoter in lymphocytes from 71
      volunteers was analyzed by using PCR. Impulsivity was defined as the number of
      commission errors (responding when one should not) recorded during a Go/No-go
      task; a larger number of commission errors indicate greater difficulty in
      inhibiting impulsive behavior. The subjects of the A-1438A allele group for the 5
      HT(2A) receptor gene made more commission errors under the punishment-reward
      (PR)condition in a Go/No-go task than those in the G-1438G group. In the present
      review, we discuss and suggest the possible involvement of the A-1438A
      polymorphism of the 5HT2A receptor gene promoter in impulsive behavior. This
      hypothesis was evaluated by using a behavioral task measure that could directly
      reveal impulsive behavioral traits in humans.

PMID- 17185513
TI  - Investigating gene-to-behavior pathways in psychiatric disorders: the use of a
      comprehensive behavioral test battery on genetically engineered mice.
AB  - We have been investigating the relationships between genes and behaviors by
      conducting a systematic and well-defined behavioral test battery with mice that
      have a mutation on a gene of interest. The behavioral test battery covers a
      relatively broad range of various behavioral domains such as learning and memory,
      sensory-motor functions, emotion, motivation, and drug sensitivity/preference.
      Recently, we subjected mice lacking calcineurin (CN), a calcium/calmodulin
      protein phosphatase, to the comprehensive behavioral test battery. The mutant
      mice had a severe working memory deficit, increased locomotor activity, decreased
      social interaction, and impairments in prepulse and latent inhibition. The
      abnormalities of CN mutant mice were strikingly similar to those described for
      schizophrenic patients. Consistent with these findings, human genetics studies in
      a large sample of affected families detected a significant association of the
      PPP3CC gene, which encodes the CN gamma catalytic subunit with schizophrenia. The
      idea that abnormalities in the CN signaling pathway are involved in schizophrenia
      pathogenesis is consistent with traditional theories of schizophrenia and with
      many facts known about schizophrenia. A tremendous amount of knowledge about CN
      has accumulated and, by utilizing this information, the studies on the
      pathogenesis/pathophysiology of schizophrenia and its related mental disorders
      will be potentially accelerated. We discuss the potential impact of a large-scale
      mouse phenotyping project on the study of psychiatric disorders.

PMID- 17185514
TI  - Animal model of schizophrenia: dysfunction of NMDA receptor-signaling in mice
      following withdrawal from repeated administration of phencyclidine.
AB  - In humans, phencyclidine (PCP), a noncompetitive N-methyl-d-aspartate (NMDA)
      antagonist, reproduces a schizophrenia-like psychosis such as positive/negative
      symptoms and cognitive deficits. PCP (10 mg/kg/day for 14 days)-treated mice
      exhibit the enhanced immobility in a forced swimming test as indexes of negative
      symptoms and impairment of latent learning in a water finding test as indexes of
      cognitive deficits. These behavioral deficits remain after withdrawal from
      repeated PCP treatment and are attenuated by atypical antipsychotics, but not by
      typical antipsychotics. Since it has been hypothesized that insufficient
      glutamate neurotransmission is involved in the pathophysiology of schizophrenia,
      we investigated an involvement of glutamatergic system in emotional and cognitive
      deficits in mice treated with PCP repeatedly. Ca(2+)/calmodulin kinase II
      (CaMKII) is markedly phosphorylated after the forced swimming test and the
      training trial of water finding test in the prefrontal cortex of saline-treated
      mice but not PCP-treated mice. Facilitation of NMDA receptor function by NMDA
      receptor glycine-site agonists such as D-cycloserine and glycine is effective on
      the abnormal intracellular signaling, and emotional and cognitive deficits in
      mice treated with PCP repeatedly. The repeated PCP treatment impaired NMDA
      receptor function and decreased levels of spontaneous extracellular glutamate in
      the prefrontal cortex, indicating that the repeated PCP treatment impairs both
      pre- and postsynaptic glutamate transmissions. Our findings suggest that abnormal
      NMDA receptor signaling is involved in the emotional and cognitive deficits in
      mice treated with PCP repeatedly. Our PCP-treated mice would be a useful model
      for studying the effect of antipsychotics on emotional and cognitive deficits in
      schizophrenia.

PMID- 17185515
TI  - Girdin, a novel actin-binding protein, and its family of proteins possess
      versatile functions in the Akt and Wnt signaling pathways.
AB  - Girdin (GIRDers of actIN filament, also reported as APE, GIV, or HkRP1) is a
      novel protein expressed ubiquitously in mammals and was recently identified as a
      binding partner of the serine/threonine kinase Akt. We found that Girdin is an
      actin-binding protein involved in both the remodeling of the actin cytoskeleton
      and in cell motility. Recent studies have uncovered new and varied functions of
      Girdin. For example, it prolongs the activation of Akt and regulates DNA
      replication in response to insulin signaling. Girdin also associates with
      heterotrimeric G proteins and dynamin (a large GTPase), which are involved in
      membrane transport. We found that Akt phosphorylates Girdin in response to growth
      factors such as epidermal growth factor (EGF) in fibroblasts. Furthermore,
      phosphorylated Girdin accumulates at the leading edge of migrating cells,
      suggesting its role in Akt-dependent cell migration or tumor invasion. To date,
      two paralogues of Girdin have been identified in mammals. One of them, Daple
      (also named HkRP2), is a binding partner and regulator of Dishevelled, an
      important cytoplasmic component of the Wnt signaling pathway. Another is a
      protein encoded by FLJ00354 (also named HkRP3), which has not been functionally
      characterized. These members are assumed to be dimers with large polypeptide
      chains (220-250 kDa) that associate at their central long coiled-coil domains.
      The amino acid sequences of the members show about 32-46% overall identity, with
      the greatest variation toward the carboxyl terminal domains that specify the
      binding partners. Here we propose roles for this family of proteins in diverse
      cellular processes.

PMID- 17185516
TI  - Biosignals modulated by tumor-associated carbohydrate antigens: novel targets for
      cancer therapy.
AB  - Based on the remodeling of glycosphingolipids on the human tumor cell lines with
      manipulation of glycosyltransferase genes, roles of sugar moieties in tumor
      associated carbohydrate antigens have been analyzed. Two main topics, that is,
      the roles of ganglioside GD3 in human malignant melanomas and those of GD2 in
      small cell lung cancer (SCLC) were reported. GD3 enhances tyrosine
      phosphorylation of two adaptor molecules, p130Cas and paxillin, resulting in the
      increased cell growth and invasion in melanoma cells. GD2 also enhances the
      proliferation and invasion of SCLC cells. GD2 also mediates apoptosis with anti
      GD2 monoclonal antibodies (mAbs) via dephosphorylation of the focal adhesion
      kinase. These approaches have promoted further understanding of mechanisms by
      which gangliosides modulate malignant properties of human cancer, and the results
      obtained here propose novel targets for cancer therapy.

PMID- 17185517
TI  - FAK signaling in neoplastic disorders: a linkage between inflammation and cancer.
AB  - Focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, is frequently
      overexpressed in various tumors and its expression shows good correlation with
      the progression of tumor. FAK is involved in a diverse range of critical cellular
      events including spreading, proliferation, migration, and invasion. In addition
      to these cellular functions, we found that FAK signaling played a critical role
      in the production of matrix metalloproteinases (MMP) such as MMP-2 and MMP-9 and
      subsequently activated tumor invasion. Moreover, we found that tumor necrosis
      factor-alpha (TNF-alpha), a proinflammatory cytokine that acts as an endogenous
      tumor promoter, activated FAK signaling and enhanced tumor invasion. Since the
      tumor microenvironment that is largely orchestrated by cytokines is a critical
      component of tumor progression, these results suggest the importance of FAK as a
      signaling molecule involved in tumorigenesis. Here, we review the general
      structure and binding partners of FAK, its regulatory mechanism, and expression
      in tumors. By summarizing our recent studies, we focus on the critical role of
      FAK that links cancer with inflammation.

PMID- 17185518
TI  - SFK-STAT pathway: an alternative and important way to malignancies.
AB  - Signal transducers and activators of transcription (STAT) proteins play a crucial
      role in mediating signals from a diverse spectrum of cytokine receptors. STAT is
      thought to be activated by JAK family kinases (JFK) in many cytokine receptor
      signal pathways; however, recent studies have demonstrated an alternative pathway
      to activate STAT by Src family kinases (SFK) in growth factor receptor signal. We
      also observed STAT5 phosphorylation by Lyn, a member of SFK, in our two recent
      studies. We introduce these studies and review the literature of STAT activation
      by SFK and aberrant activation of STAT by oncogenic signals.

PMID- 17185519
TI  - Pharmacogenetic approach for cancer treatment-tailored medicine in practice.
AB  - This article focuses on pharmacogenetic associations between genetic polymorphism
      of uridine diphosphate glucuronosyltransferase (UGT) 1A1 gene and irinotecan
      toxicity. Accumulating evidence provides support to the idea that determination
      of UGT1A1 polymorphisms before irinotecan treatment is clinically useful and
      important for predicting and avoiding related toxicities. On the basis of these
      backgrounds, the irinotecan label was updated in 2005 in the United States to
      provide pharmacogenetic information, and a dose reduction of irinotecan should be
      considered for patients known to be homozygous for the UGT1A1*28 allele when
      administered in combination with other agents or a single agent. The
      irinotecan/UGT1A1 issue and the development of molecular diagnostic testing are
      now to be translated into clinical practice.

PMID- 17185520
TI  - Involvement of DPPIV/CD26 in epithelial morphology and suppressed invasive
      ability in ovarian carcinoma cells.
AB  - Dipeptidyl peptidase IV (DPPIV) is a multifunctional cell surface aminopeptidase
      with ubiquitous expression and it has a variety of functional properties in the
      development of human malignancies. In the present study, we showed the possible
      correlation between DPPIV/CD26 expression and less migratory potential with
      decreased MMP-2 expression in ovarian carcinoma cells. Moreover, induction of
      DPPIV/CD26 resulted in reduced expressions of MMP-2 and mesenchymal markers such
      as vimentin and SMA, with a less invasive potential and an epithelial morphologic
      change. This evidence implies that DPPIV/CD26 may play a crucial role in the
      antimetastatic potential in ovarian carcinoma.

PMID- 17185521
TI  - Integrated molecular medicine for neuronal and neoplastic disorders. Proceedings
      of the Third International COE Symposium on Elucidation of Pathogenesis and
      Therapy Development for Neurological and Psychiatric Disorders. December 1-2,
      2005. Nagoya, Japan.

PMID- 17185522
TI  - The drug wars.

PMID- 17185526
TI  - Refutation of "the myth of the female athlete triad".

PMID- 17185528
TI  - Correction of misinterpretations and misrepresentations of the female athlete
      triad.

PMID- 17185529
TI  - The first filamentous fungal genome sequences: Aspergillus leads the way for
      essential everyday resources or dusty museum specimens?
AB  - The published Aspergillus genome sequences (A. nidulans, A. fumigatus, A. oryzae)
      and further sequence data from A. clavatus, Neosartorya fischeri, A. flavus, A.
      niger, A. parasiticus and A. terreus are the first from a group of related
      filamentous fungi. They indicate the gains possible from genomic approaches, but
      also problems that arise after the sequences are finished. Benefits include a
      greater understanding of genome structure and evolution, insights into gene
      regulation, predictions of new factors that may be relevant to pathogenicity and
      the discovery of novel enzymes with biotechnological value. Areas where further
      developments are needed include gene and structure-function predictions, methods
      for comparative genome analysis and the interfaces for access to genome
      information. In addition, strategies for continued maintenance and updating need
      to be developed at the start of the post-genomic era to increase the value of
      genome sequences into the future.

PMID- 17185530
TI  - The first fifty microarray studies in filamentous fungi.
AB  - Microarray studies have examined global gene expression in over 20 species of
      filamentous fungi encompassing a wide variety of research areas. The majority
      have addressed aspects of metabolism or pathogenicity. Metabolic studies have
      revealed important differences in the transcriptional regulation of genes for
      primary metabolic pathways between filamentous fungi and yeast. Transcriptional
      profiles for genes involved in secondary metabolism have also been established.
      Genes required for the biosynthesis of both useful and detrimental secondary
      metabolites have been identified. Due to the economic, ecological and medical
      implications, it is not surprising that many studies have used microarray
      analysis to examine gene expression in pathogenic filamentous fungi. Genes
      involved in various stages of pathogenicity have been identified, including those
      thought to be important for adaptation to the host environment. While most of the
      studies have simulated pathogenic conditions in vitro, a small number have also
      reported fungal gene expression within their plant hosts. This review summarizes
      the first 50 microarray studies in filamentous fungi and highlights areas for
      future investigation.

PMID- 17185531
TI  - An rhl-like quorum-sensing system negatively regulates pyoluteorin production in
      Pseudomonas sp. M18.
AB  - Pseudomonas sp. M18, isolated from the watermelon rhizosphere, is antagonistic
      against a number of soil-borne pathogens. This strain produces an uncharacterized
      red pigment, pyoluteorin (Plt), and two N-acylhomoserine lactones (AHLs). A
      previously isolated red-pigment-defective mutant, M18-T510, contains an insert
      within a gene similar to rhlI in P. aeruginosa PAO1. The M18 rhlI gene product is
      responsible for the production of two AHL signals: N-butyryl-homoserine lactone
      and N-hexanoylhomoserine lactone. Mutants defective in either rhlI or rhlR showed
      enhanced Plt biosynthesis due to loss of transcriptional repression, which was
      mediated, at least in part, by suppressed expression of the activator PltR. A Plt
      specific ABC transporter was also upregulated in the rhl mutants in a Plt
      dependent manner. In comparison with the wild-type strain, the rhl mutants
      survived longer during stationary-phase growth.

PMID- 17185532
TI  - The iron- and cAMP-regulated gene SIT1 influences ferrioxamine B utilization,
      melanization and cell wall structure in Cryptococcus neoformans.
AB  - The mechanisms by which pathogens sense and transport iron are important during
      infection, because of the low availability of free iron in the mammalian host.
      Iron is a key nutritional cue for the pathogen Cryptococcus neoformans, because
      it influences expression of the polysaccharide capsule that is the major
      virulence factor of the fungus. In this study, C. neoformans mutants were
      constructed with a defect in the iron-regulated gene SIT1 that encodes a putative
      siderophore iron transporter. Analysis of mutants in serotype A and D strains
      demonstrated that SIT1 is required for the use of siderophore-bound iron, and for
      growth in a low-iron environment. The sit1 mutants also showed changes in melanin
      formation and cell wall density, and it was found that mutants defective in
      protein kinase A, which is known to influence melanization and capsule formation,
      showed elevated SIT1 transcripts in both the serotype A and the serotype D
      backgrounds. Finally, the mutants were tested for virulence in a murine model of
      cryptococcosis, and it was found that SIT1 was not required for virulence.
      Overall, these studies establish links between iron acquisition, melanin
      formation and cAMP signalling in C. neoformans.

PMID- 17185533
TI  - Expression of furA is modulated by NtcA and strongly enhanced in heterocysts of
      Anabaena sp. PCC 7120.
AB  - Fur (ferric uptake regulator) proteins are principally responsible for
      maintaining iron homeostasis in prokaryotes. Iron is usually a scarce resource.
      Its limitation reduces photosynthetic rates and cell growth in cyanobacteria in
      general and especially in cyanobacteria that are fixing dinitrogen, a process
      that requires the synthesis of numerous proteins with a high content of iron.
      This paper shows that in the diazotrophic cyanobacterium Anabaena sp. strain PCC
      7120, levels of furA mRNA and FurA protein increase significantly in response to
      nitrogen deprivation, and that furA up-regulation takes place specifically in
      proheterocysts and mature heterocysts. Great differences in a Northern blot,
      probed with furA, of RNA from an ntcA mutant relative to wild-type Anabaena sp.
      were attributable to binding of NtcA, a global regulator of nitrogen metabolism,
      to the promoter of furA and to the promoter of the furA antisense transcript
      alr1690-alpha-furA.

PMID- 17185534
TI  - Autophagy in the pathogen Candida albicans.
AB  - Autophagy is a major cellular process that facilitates the bulk degradation of
      eukaryotic macromolecules and organelles, through degradation within the
      lysosomal/vacuole compartment. This has been demonstrated to influence a diverse
      array of eukaryotic cell functions including adaptation, differentiation and
      developmental programmes. For example, in Saccharomyces cerevisiae autophagy is
      required for sporulation and survival of nitrogen starvation. The opportunistic
      pathogen Candida albicans has the ability to colonize and cause disease within a
      diverse range of mammalian host sites. The ability to adapt and differentiate
      within the host is liable to be critical for host colonization and infection.
      Previous results indicated that the vacuole plays an important role in C.
      albicans adaptation to stress, differentiation, and survival within and injury of
      host cells. In this study the importance of vacuole-mediated degradation through
      the process of autophagy was investigated. This involved identification and
      deletion of ATG9, a C. albicans gene required for autophagy. The deletion strain
      was blocked in autophagy and the closely related cytoplasm to vacuole (cvt)
      trafficking pathway. This resulted in sensitivity to nitrogen starvation, but no
      defects in growth rate, vacuole morphology or resistance to other stresses. This
      indicates that the mutant has specific defects in autophagy/cvt trafficking.
      Given the importance of autophagy in the development and differentiation of other
      eukaryotes, it was surprising to find that the atg9Delta mutant was unaffected in
      either yeast-hypha or chlamydospore differentiation. Furthermore, the atg9Delta
      mutant survived within and killed a mouse macrophage-like cell line as
      efficiently as control strains. The data suggest that autophagy plays little or
      no role in C. albicans differentiation or during interaction with host cells.

PMID- 17185535
TI  - A conserved extended signal peptide region directs posttranslational protein
      translocation via a novel mechanism.
AB  - Members of the type V secretion family are among the most prevalent secreted
      proteins in Gram-negative bacteria. A subset of this family, including Pet, the
      prototypical member of the Enterobacteriaceae serine proteases, possess unusual
      signal peptides which can be divided into five regions termed N1 (charged), H1
      (hydrophobic), N2, H2 and C (cleavage site) domains. The N1 and H1 regions, which
      the authors have named the extended signal peptide region (ESPR), demonstrate
      remarkable conservation. In contrast, the N2, H2 and C regions show significant
      variability, and are reminiscent of typical Sec-dependent signal sequences.
      Despite several investigations, the function of the ESPR remains obscure. Here,
      it is shown that proteins possessing the ESPR are translocated in a
      posttranslational fashion. The presence of the ESPR severely impairs inner
      membrane translocation. Mutational analysis suggests that the ESPR delays inner
      membrane translocation by adopting a particular conformation, or by interacting
      with a cytoplasmic or inner membrane co-factor, prior to inner membrane
      translocation.

PMID- 17185536
TI  - Functional characterization of IScs605, an insertion element carried by
      tetracycline-resistant Chlamydia suis.
AB  - Stable tetracycline resistance in Chlamydia suis is mediated by a family of
      genomic islands [the tet(C) islands] that are integrated into the chlamydial
      chromosome. The tet(C) islands contain several plasmid-specific genes, the tet(C)
      resistance gene and, in most cases, a novel insertion element (IScs605) encoding
      two predicted transposases. The hypothesis that IScs605 mediated the integration
      of the tet(C) resistance islands into the C. suis genome was tested using a
      plasmid-based transposition system in Escherichia coli. Both high- and medium
      copy-number plasmids were used as carriers of IScs605 in these experiments.
      IScs605 integrated into a target plasmid (pOX38) when delivered by either donor
      plasmid, and integration of the entire donor plasmid was common. IScs605-mediated
      integration occurred at many positions within pOX38, with 36 of 38 events
      adjacent to a 5'-TTCAA-3' sequence. Deletions in each of the candidate
      transposase genes within IScs605 demonstrated that only one of the two ORFs was
      necessary for the observed transposition activity and target specificity.
      Analysis of progeny from the mating assays also indicated that IScs605 can excise
      following integration into a target DNA, and, in each tested case, the sequence
      5'-AATTCAA-3' remained at the site of excision. Collectively, these results are
      consistent with the nucleotide sequence data collected for the tet(C) islands,
      and strongly suggest that a transposase within IScs605 is responsible for
      integration of these genomic islands into the C. suis chromosome.

PMID- 17185537
TI  - The dimeric repressor SoxR binds cooperatively to the promoter(s) regulating
      expression of the sulfur oxidation (sox) operon of Pseudaminobacter
      salicylatoxidans KCT001.
AB  - Sulfur oxidation in Pseudaminobacter salicylatoxidans KCT001 is rendered by the
      combined action of several enzymes encoded by a thiosulfate-inducible sox operon.
      In this study it has been conclusively demonstrated by insertional mutagenesis
      that the regulatory gene of this operon is soxR, which encodes a DNA-binding
      protein belonging to the ArsR-SmtB family. SoxR was found to bind to two promoter
      operator segments within the sox cluster, of which the one (wx) located between
      soxW and soxX controls the expression of sulfur-oxidation genes soxX through soxD
      while the other, a bi-directional element (sv) located between soxS and soxV,
      controls the expression of soxVW in one direction and the putative regulatory
      cluster soxSRT in the other. In the case of the wx promoter the repressor was
      found to bind in a cooperative manner to two distinct binding sites having
      different affinities, while in the case of the sv promoter binding occurred at a
      symmetric dimeric site and involved a higher degree of cooperativity. The high
      degree of cooperativity observed in the binding of SoxR to its target sites
      seemed to be due to the propensity of SoxR monomers to form dimers. The apparent
      dissociation constants of the SoxR-operator complexes were in the nanomolar
      range, indicating relatively strong interactions. It was demonstrated using a
      reporter system in Escherichia coli that this high-affinity binding of SoxR led
      to efficient repression in trans. Thus the role of SoxR as a repressor of the sox
      operon has not only been conclusively established but it has also been shown that
      this repression is brought about through cooperative interactions of SoxR with
      dimeric binding sites that occlude the operon promoters.

PMID- 17185538
TI  - Regulatory role of RsgI in sigI expression in Bacillus subtilis.
AB  - The sigma gene, sigI, of Bacillus subtilis belongs to the group IV heat-shock
      response genes and has many orthologues in the bacterial phylum Firmicutes. The
      B. subtilis sigI gene is considered to constitute an operon with rsgI (regulation
      of sigI, formerly ykrI). As little is known about either the structure and
      function of the sigI-rsgI operon or the SigI regulons, the role of RsgI in heat
      inducible transcription of the sigI-rsgI operon was investigated, using Northern
      analysis and a heat-stable beta-galactosidase reporter assay. Heat-inducible,
      SigI-dependent transcription of the sigI-rsgI operon was stimulated greatly by
      disrupting rsgI. Yeast two-hybrid analysis showed direct interaction between the
      N-terminal portion of the presumed RsgI protein and SigI. Without RsgI function,
      induction of transcription of the sigI-rsgI operon upon transient heat stress
      depended on dnaK activity. However, transcription of the operon was induced
      during growth at prolonged higher temperature even without DnaK function. Without
      RsgI function, sigI-rsgI operon transcription was induced after the end of growth
      independent of any temperature shift in a sporulation medium and toward the end
      of growth in a rich complex medium. Furthermore, glucose addition resulted in a
      strong suppression of sigI-rsgI transcription. Therefore it is hypothesized that
      transcription of the sigI-rsgI operon of B. subtilis is negatively regulated by
      the putative transmembrane protein RsgI, which moderates SigI's sensitivity to
      heat shock or nutritional stress.

PMID- 17185539
TI  - Differential expression of two bc1 complexes in the strict acidophilic
      chemolithoautotrophic bacterium Acidithiobacillus ferrooxidans suggests a model
      for their respective roles in iron or sulfur oxidation.
AB  - Three strains of the strict acidophilic chemolithoautotrophic Acidithiobacillus
      ferrooxidans, including the type strain ATCC 23270, contain a petIIABC gene
      cluster that encodes the three proteins, cytochrome c1, cytochrome b and a Rieske
      protein, that constitute a bc1 electron-transfer complex. RT-PCR and Northern
      blotting show that the petIIABC cluster is co-transcribed with cycA, encoding a
      cytochrome c belonging to the c4 family, sdrA, encoding a putative short-chain
      dehydrogenase, and hip, encoding a high potential iron-sulfur protein, suggesting
      that the six genes constitute an operon, termed the petII operon. Previous
      results indicated that A. ferrooxidans contains a second pet operon, termed the
      petI operon, which contains a gene cluster that is similarly organized except
      that it lacks hip. Real-time PCR and Northern blot experiments demonstrate that
      petI is transcribed mainly in cells grown in medium containing iron, whereas
      petII is transcribed in cells grown in media containing sulfur or iron. Primer
      extension experiments revealed possible transcription initiation sites for the
      petI and petII operons. A model is presented in which petI is proposed to encode
      the bc1 complex, functioning in the uphill flow of electrons from iron to NAD(P),
      whereas petII is suggested to be involved in electron transfer from sulfur (or
      formate) to oxygen (or ferric iron). A. ferrooxidans is the only organism, to
      date, to exhibit two functional bc1 complexes.

PMID- 17185540
TI  - A sigma54-dependent promoter in the regulatory region of the Escherichia coli
      rpoH gene.
AB  - The Escherichia coli rpoH gene is transcribed from four known and differently
      regulated promoters: P1, P3, P4 and P5. This study demonstrates that the
      conserved consensus sequence of the sigma54 promoter in the regulatory region of
      the rpoH gene, described previously, is a functional promoter, P6. The evidence
      for this conclusion is: (i) the specific binding of the sigma54-RNAP holoenzyme
      to P6, (ii) the location of the transcription start site at the predicted
      position (C, 30 nt upstream of ATG) and (iii) the dependence of transcription on
      sigma54 and on an ATP-dependent activator. Nitrogen starvation, heat shock,
      ethanol and CCCP treatment did not activate transcription from P6 under the
      conditions examined. Two activators of sigma54 promoters, PspF and NtrC, were
      tested but neither of them acted specifically. Therefore, PspFDeltaHTH, a
      derivative of PspF, devoid of DNA binding capability but retaining its ATPase
      activity, was used for transcription in vitro, taking advantage of the relaxed
      specificity of ATP-dependent activators acting in solution. In experiments in
      vivo overexpression of PspFDeltaHTH from a plasmid was employed. Thus, the
      sigma54-dependent transcription capability of the P6 promoter was demonstrated
      both in vivo and in vitro, although the specific conditions inducing initiation
      of the transcription remain to be elucidated. The results clearly indicate that
      the closed sigma54-RNAP-promoter initiation complex was formed in vitro and in
      vivo and needed only an ATP-dependent activator to start transcription.

PMID- 17185541
TI  - Three functional subdomains of the Escherichia coli FtsQ protein are involved in
      its interaction with the other division proteins.
AB  - FtsQ, an essential protein for the Escherichia coli divisome assembly, is able to
      interact with various division proteins, namely FtsI, FtsL, FtsN, FtsB and FtsW.
      In this paper, the FtsQ domains involved in these interactions were identified by
      two-hybrid assays and co-immunoprecipitations. Progressive deletions of the ftsQ
      gene suggested that the FtsQ self-interaction and its interactions with the other
      proteins are localized in three periplasmic subdomains: (i) residues 50-135
      constitute one of the sites involved in FtsQ, FtsI and FtsN interaction, and this
      site is also responsible for FtsW interaction; (ii) the FtsB interaction is
      localized between residues 136 and 202; and (iii) the FtsL interaction is
      localized at the very C-terminal extremity. In this third region, the interaction
      site for FtsK and also the second site for FtsQ, FtsI, FtsN interactions are
      located. As far as FtsW is concerned, this protein interacts with the fragment of
      the FtsQ periplasmic domain that spans residues 67-75. In addition, two protein
      subdomains, one constituted by residues 1-135 and the other from 136 to the end,
      are both able to complement an ftsQ null mutant. Finally, the unexpected finding
      that an E. coli ftsQ null mutant can be complemented, at least transiently, by
      the Streptococcus pneumoniae divIB/ftsQ gene product suggests a new strategy for
      investigating the biological significance of protein-protein interactions.

PMID- 17185542
TI  - Structural and genetic evidence that the Escherichia coli O148 O antigen is the
      precursor of the Shigella dysenteriae type 1 O antigen and identification of a
      glucosyltransferase gene.
AB  - Shigella dysenteriae type 1 is the most virulent serotype of Shigella.
      Enterotoxigenic Escherichia coli O148 is pathogenic and can cause diarrhoea. The
      following structure was established for the tetrasaccharide repeating unit of the
      E. coli O148 O antigen: -->3)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-D
      Glcp-(1-->3)-alpha-D-GlcpNAc-(1-->. This differs from the structure reported
      earlier for S. dysenteriae type 1 by having a glucose (Glc) residue in place of a
      galactose (Gal) residue. The two bacteria also have the same genes for O antigen
      synthesis, with the same organization and high level of DNA identity, except that
      in S. dysenteriae type 1 wbbG is interrupted by a deletion, and a
      galactosyltransferase gene wbbP located on a plasmid is responsible for the
      transfer of galactose to make a novel antigenic epitope of the O antigen. The S.
      dysenteriae type 1 O antigen was reconstructed by replacing the E. coli O148 wbbG
      gene with the wbbP gene, and it had the LPS structure and antigenic properties of
      S. dysenteriae type 1, indicating that the S. dysenteriae type 1 O antigen
      evolved from that of E. coli O148. It was also confirmed that wbbG of E. coli
      O148 is a glucosyltransferase gene, and two serotype-specific genes of E. coli
      O148 and S. dysenteriae type 1 were identified.

PMID- 17185543
TI  - The proteomic profile of Fusobacterium nucleatum is regulated by growth pH.
AB  - Fusobacterium nucleatum is a saccharolytic Gram-negative anaerobic organism
      believed to play an important role in the microbial succession associated with
      the development of periodontal disease. Its genome contains niche-specific genes
      shared with the other inhabitants of dental plaque, which may help to explain its
      ability to survive and grow in the changing environmental conditions experienced
      in the gingival sulcus during the transition from health to disease. The pH of
      the gingival sulcus increases during the development of periodontitis and this is
      thought to occur by the metabolism of nutrients supplied by gingival crevicular
      fluid. In comparison with other plaque inhabitants, F. nucleatum has the greatest
      ability to neutralize acidic environments. The differential expression of soluble
      cytoplasmic proteins induced by acidic (pH 6.4) or basic (pH 7.4 and 7.8)
      conditions, during long-term anaerobic growth in a chemostat, was identified by
      two-dimensional gel electrophoresis and image analysis software. Twenty-two
      proteins, found to have altered expression in response to external pH, were
      identified by tryptic digestion and mass spectrometry. Eight differentially
      expressed proteins associated with increased energy (ATP) production via the 2
      oxoglutarate and Embden-Meyerhof pathways appeared to be directed towards either
      cellular biosynthesis or the maintenance of internal homeostasis. Overall, these
      results represent the first proteomic investigation of F. nucleatum and the
      identification of gene products which may be important in the organism's
      persistence during the transition from health to disease in vivo.

PMID- 17185544
TI  - Rickettsiae phylogeny: a multigenic approach.
AB  - The development of molecular taxonomic methods has provided a large amount of
      data in the reorganization of Rickettsiae taxonomy. Nevertheless, phylogenetic
      relationships among some groups and species delimitation remain unclear. To
      clarify rickettsial phylogeny, a multigenic approach was used for the first time
      for the genus Rickettsia, based on simultaneous analyses of eight loci: atpA,
      recA, virB4, dnaA, dnaK, rrl-rrf internal transcribed spacer, ompA and gltA.
      Concatenation of different nucleotide sequences resulted in an improvement in
      phylogenetic resolution when compared to single gene data. This multigenic
      approach has enabled the differentiation of many groups, including the spotted
      fever group which includes a great number of closely related species. The
      reliability of some previously recognized groups was evaluated.

PMID- 17185545
TI  - Phenotypic and molecular characterizations of Yersinia pestis isolates from
      Kazakhstan and adjacent regions.
AB  - Recent interest in characterizing infectious agents associated with bioterrorism
      has resulted in the development of effective pathogen genotyping systems, but
      this information is rarely combined with phenotypic data. Yersinia pestis, the
      aetiological agent of plague, has been well defined genotypically on local and
      worldwide scales using multi-locus variable number tandem repeat analysis (MLVA),
      with emphasis on evolutionary patterns using old isolate collections from
      countries where Y. pestis has existed the longest. Worldwide MLVA studies are
      largely based on isolates that have been in long-term laboratory culture and
      storage, or on field material from parts of the world where Y. pestis has
      potentially circulated in nature for thousands of years. Diversity in these
      isolates suggests that they may no longer represent the wild-type organism
      phenotypically, including the possibility of altered pathogenicity. This study
      focused on the phenotypic and genotypic properties of 48 Y. pestis isolates
      collected from 10 plague foci in and bordering Kazakhstan. Phenotypic
      characterization was based on diagnostic tests typically performed in reference
      laboratories working with Y. pestis. MLVA was used to define the genotypic
      relationships between the central-Asian isolates and a group of North American
      isolates, and to examine Kazakh Y. pestis diversity according to predefined
      plague foci and on an intermediate geographical scale. Phenotypic properties
      revealed that a large portion of this collection lacks one or more plasmids
      necessary to complete the blocked flea/mammal transmission cycle, has lost Congo
      red binding capabilities (Pgm-), or both. MLVA analysis classified isolates into
      previously identified biovars, and in some cases groups of isolates collected
      within the same plague focus formed a clade. Overall, MLVA did not distinguish
      unique phylogeographical groups of Y. pestis isolates as defined by plague foci
      and indicated higher genetic diversity among older biovars.

PMID- 17185547
TI  - Growth of the genetically engineered strain Cupriavidus necator RW112 with
      chlorobenzoates and technical chlorobiphenyls.
AB  - Cupriavidus necator (formerly Ralstonia eutropha) strain H850 is known to grow on
      biphenyl, and to co-oxidize congeners of polychlorinated biphenyls (PCBs). Using
      a Tn5-based minitransposon shuttle system and the TOL plasmid, the rational
      construction of hybrids of H850 was achieved by subsequent introduction of three
      distinct elements carrying 11 catabolic loci from three other biodegrading
      bacteria into the parent strain, finally yielding C. necator RW112. The new
      genetic elements introduced into H850 and its derivatives were tcbRCDEF, which
      encode the catabolic enzymes needed for chlorocatechol biodegradation under the
      control of a transcriptional regulator, followed by cbdABC, encoding a 2
      halobenzoate dioxygenase, and xylXYZ, encoding a broad-spectrum toluate
      dioxygenase. The expression of the introduced genes was demonstrated by measuring
      the corresponding enzymic activities. The engineered strain RW112 gained the
      ability to grow on all isomeric monochlorobenzoates and 3,5-dichlorobenzoate, all
      monochlorobiphenyls, and 3,5-dichloro-, 2,3'-dichloro- and 2,4'-dichlorobiphenyl,
      without accumulation of chlorobenzoates. It also grew and utilized two commercial
      PCB formulations, Aroclor 1221 and Aroclor 1232, as sole carbon and energy
      sources for growth. This is the first report on the aerobic growth of a
      genetically improved bacterial strain at the expense of technical Aroclor
      mixtures.

PMID- 17185546
TI  - Abundance and ecophysiology of Defluviicoccus spp., glycogen-accumulating
      organisms in full-scale wastewater treatment processes.
AB  - The activity of glycogen-accumulating organisms (GAOs) in enhanced biological
      phosphorus removal (EBPR) wastewater treatment plants has been proposed as one
      cause of deterioration of EBPR. Putative GAOs from the Alphaproteobacteria,
      Defluviicoccus spp. (including D. vanus), were studied in full-scale EBPR plants
      to determine their distribution, abundance and ecophysiology. Fluorescence in
      situ hybridization (FISH) demonstrated that Defluviicoccus spp. were generally
      low in abundance; however, in one plant surveyed, Cluster 2 Defluviicoccus
      constituted 9 % of all Bacteria. FISH combined with microautoradiography revealed
      that both Cluster 1 and Cluster 2 Defluviicoccus were capable of taking up a
      narrow range of substrates including acetate, propionate, pyruvate and glucose
      under anaerobic and aerobic conditions. Formate, butyrate, ethanol and several
      other substrates were not taken up. Cluster 2 Defluviicoccus demonstrated a
      phenotype consistent with the current metabolic model for GAOs--anaerobic
      assimilation of acetate and reduction to polyhydroxyalkanoates (PHA) using the
      glycolytic pathway, and aerobic consumption of PHA. Polyphosphate-accumulating
      organisms (PAOs, 'Candidatus Accumulibacter phosphatis') and other putative GAOs
      ('Candidatus Competibacter phosphatis') co-existed in two plants with Cluster 2
      Defluviicoccus, but in both plants, the latter organisms were more abundant. Thus
      Cluster 2 Defluviicoccus can be relatively abundant and could be carbon
      competitors of PAOs and other GAOs in EBPR plants.

PMID- 17185548
TI  - Proteomic comparison of Mycobacterium avium subspecies paratuberculosis grown in
      vitro and isolated from clinical cases of ovine paratuberculosis.
AB  - Paratuberculosis (Johne's disease) poses a significant economic problem to beef,
      dairy and sheep industries worldwide, and is caused by Mycobacterium avium
      subspecies paratuberculosis. In this study, 2D PAGE was used as a tool to
      investigate the virulent state of M. avium subsp. paratuberculosis, incorporating
      the technique of beating the organism with zirconium/silica beads to provide a
      comprehensive representation of its proteome. A direct comparison of the
      proteomes of M. avium subsp. paratuberculosis scraped from the terminal ileum of
      ovine paratuberculosis cases, and the identical strain grown in vitro, is
      presented. These analyses identified a set of 10 proteins whose expression is
      upregulated during natural infection: 1-pyrroline-5-carboxylate dehydrogenase
      (RocA), a putative acyl-CoA dehydrogenase (FadE14), 2-methylcitrate dehydratase
      (2-mcd), arginosuccinate synthase (ArgG), universal stress protein (usp), 30S
      ribosomal protein S2 (RpsB), peptidyl-prolyl cis-trans isomerase (PpiA),
      luciferase-like monooxygenase (lmo), thiosulfate sulfurtransferase (SseA) and ATP
      dependent Clp protease (ClpB). Most of the proteins identified do not have
      obviously related functions; however, ArgG and RocA function in the same pathway,
      and may have a concerted action for energy production in vivo.

PMID- 17185549
TI  - Proteomic identification and characterization of bacterial factors associated
      with Burkholderia cenocepacia survival in a murine host.
AB  - Burkholderia cenocepacia is a member of the Burkholderia cepacia complex, a
      diverse family of Gram-negative bacteria that are serious respiratory pathogens
      in immunocompromised patients and individuals with cystic fibrosis. To identify
      putative bacterial virulence determinants, proteomic profiles were compared
      between two B. cenocepacia isolates that demonstrated differential persistence in
      a mouse model of pulmonary infection; clinical isolate C1394 is rapidly cleared
      from the murine lung whereas the strain variant, C1394mp2, persists. Two
      dimensional (2D) gel electrophoresis was used to identify candidate proteins
      involved in B. cenocepacia survival in a susceptible host. The 2D proteome of the
      persistent isolate (C1394mp2) revealed loss of an alkyl hydroperoxide reductase
      subunit C (AhpC) protein spot and increased production of flagellin proteins.
      Loss of AhpC expression in C1394mp2 correlated with enhanced susceptibility to
      oxidative stress. C1394mp2 expressed increased flagellin production and enhanced
      swimming motility, traits that were subject to regulation by heat and low pH.
      Together, these results revealed differential expression and stress regulation of
      putative virulence determinants associated with B. cenocepacia persistence in a
      susceptible host.

PMID- 17185550
TI  - The haem-haemopexin utilization gene cluster (hxuCBA) as a virulence factor of
      Haemophilus influenzae.
AB  - Haemophilus influenzae has an absolute growth requirement for a porphyrin source,
      which can be supplied in vitro by haem, haemoglobin, or the haemoglobin
      haptoglobin, haem-haemopexin and haem-albumin complexes. Utilization of the haem
      haemopexin complex is known to be mediated by the products of the hxuCBA gene
      cluster. It was demonstrated that hxuC, but not hxuA or hxuB, is also essential
      for the utilization of haem from haem-albumin complexes. Mutants of the type b
      strain E1a lacking genes in the hxuCBA gene cluster were examined for their
      ability to cause bacteraemia in rat models of invasive disease. In 5-day-old
      rats, mutants in the hxuCBA genes yielded a significantly reduced bacteraemic
      titre compared to the wild-type strain. In addition, 5-day-old rats infected with
      the hxuCBA mutant strains exhibited significantly improved survival rates
      compared to those infected with the wild-type strain. Mutations in the
      haemoglobin/haemoglobin-haptoglobin-binding protein genes (hgps), either alone or
      in combination with the hxuCBA mutations, had no impact on virulence in 5-day-old
      rats. In 30-day-old rats infected with either the hxuCBA mutants or the wild-type
      strains, there was no significant difference in the ability to establish
      bacteraemia although bacterial titres were lower in rats infected with the hxuCBA
      mutants than in those infected with the wild-type strain. These age-related
      differences in the impact of mutations in the hxuCBA gene cluster may be related
      to changes in levels of host haem-binding proteins during development of the rat.

PMID- 17185552
TI  - The glutamate-dependent acid resistance system in Escherichia coli: essential and
      dual role of the His-Asp phosphorelay RcsCDB/AF.
AB  - The RcsCDB signal transduction system is an atypical His-Asp phosphorelay.
      Notably, the response regulator RcsB can be activated either by phosphorylation
      through the RcsCD pathway or by an accessory cofactor RcsA. Although conserved in
      Enterobacteriaceae, the role of this system in adaptation to environmental stress
      conditions is largely unknown. This study reveals that the response regulator
      RcsB is essential to glutamate-dependent acid resistance, a condition pertinent
      to the lifestyle of Escherichia coli. The requirement for RcsB is independent of
      its activation by either the RcsCD or the RcsA pathway. The basal activity of
      RcsB appears to be necessary and sufficient for acid resistance. The sensitivity
      of the rcsB strain to low pH is correlated to a strong reduction of the
      expression of the glutamate decarboxylase genes, gadA and gadB, during the
      stationary phase of growth. This effect on gadA/B expression is not mediated by
      the general stress sigma factor RpoS, but does require a functional gadE allele
      and the previously identified GadE box. Therefore activation of gadAB expression
      and acid resistance absolutely requires both GadE and RcsB. In contrast, an
      increase in RcsB activity through the activation of the RcsCD phosphorelay or the
      RcsA pathway or through overproduction of the protein leads to general repression
      of the expression of the gad genes and a corresponding reduction in acid
      resistance.

PMID- 17185551
TI  - Quorum-sensing-deficient (lasR) mutants emerge at high frequency from a
      Pseudomonas aeruginosa mutS strain.
AB  - In Pseudomonas aeruginosa, quorum sensing constitutes a highly complex cell-to
      cell communication system that, along with the cognate acylhomoserine lactone
      signals and regulators LasR and RhlR, modulates the production of virulence
      factors and a wide range of metabolic functions. In a previous paper, the authors
      reported that mismatch repair disruption in P. aeruginosa results in the
      spontaneous and reproducible emergence of defined morphological colony variants
      after a relatively short period of cultivation in an aerated rich medium, in
      contrast to the non-mutator parental strain, which does not display any kind of
      diversification under identical incubation conditions. One of the morphotypical
      variants, mS2, emerges at a high frequency and displays differences in virulence
      traits that could be regulated by major quorum-sensing regulators. The present
      study shows that mutS mS2 variants had defective LasR function due to simple but
      different point mutations along the lasR gene sequence, indicating that LasR
      inactivation is the main cause of mS2 phenotypic diversification. Moreover, it
      was determined that a non-functional LasR would confer a selective advantage in
      the late stationary phase, since viability was notably higher for mS2.
      Interestingly, in all mS2 variants analysed, no sequence alterations were found
      in the gacA and rhlR genes, suggesting that the selective pressures for GacA/RhlR
      and LasR were not the same and differed from those in other Pseudomonas species,
      which, when incubated in nutrient-rich liquid stationary-phase cultures, show
      specific high instability in the gacA-gacS genes.

PMID- 17185553
TI  - The influence of ribosome modulation factor on the survival of stationary-phase
      Escherichia coli during acid stress.
AB  - Ribosome modulation factor (RMF) was shown to have an influence on the survival
      of Escherichia coli under acid stress during stationary phase, since the
      viability of cultures of a mutant strain lacking functional RMF decreased more
      rapidly than that of the parent strain at pH 3. Loss of ribosomes was observed in
      both strains when exposed to low pH, although this occurred at a higher rate in
      the RMF-deficient mutant strain, which also suffered from higher levels of rRNA
      degradation. It was concluded that the action of RMF in limiting the damage to
      rRNA contributed to the protection of E. coli under acid stress. Expression of
      the rmf gene was lower during stationary phase after growth in acidified media
      compared to media containing no added acid, and the increased rmf expression
      associated with transition from exponential phase to stationary phase was much
      reduced in acidified media. It was demonstrated that RMF was not involved in the
      stationary-phase acid-tolerance response in E. coli by which growth under acidic
      conditions confers protection against subsequent acid shock. This response was
      sufficient to overcome the increased vulnerability of the RMF-deficient mutant
      strain to acid stress at pH values between 6.5 and 5.5.

PMID- 17185554
TI  - Expression of the htrB gene is essential for responsiveness of Salmonella
      typhimurium and Campylobacter jejuni to harsh environments.
AB  - In Campylobacter jejuni, an htrB homologous gene is located in the lipo
      oligosaccharide synthesis gene cluster. This study examined the effects of htrB
      expression on the responsiveness of Salmonella typhimurium and C. jejuni to harsh
      environments. Complementation experiments showed that the C. jejuni htrB gene
      could restore the normal morphology of the Salmonella htrB mutant, and its
      ability to grow without inhibition under heat, acid and osmotic stresses, but not
      bile stress. This indicated that the htrB genes in C. jejuni and S. typhimurium
      exhibit similar pleiotropic effects. Moreover, quantitative real-time RT-PCR
      showed that expression of the C. jejuni htrB gene was upregulated under acid,
      heat, oxidative and osmotic stresses, but did not change under bile stress. This
      indicated that the C. jejuni htrB gene plays a role in regulating cell responses
      to various environmental changes. Furthermore, deletion mutation of the htrB gene
      in C. jejuni was lethal, indicating that the htrB gene is essential for C. jejuni
      survival. Therefore, these results showed that expression of the htrB gene is
      essential for the response of S. typhimurium and C. jejuni to environmental
      stresses.

PMID- 17185556
TI  - Biochemical and genetic characterization of the pathways for trehalose metabolism
      in Propionibacterium freudenreichii, and their role in stress response.
AB  - Propionibacterium freudenreichii accumulates high levels of trehalose, especially
      in response to stress. The pathways for trehalose metabolism were characterized,
      and their roles in response to osmotic, oxidative and acid stress were studied.
      Two pathways were identified: the trehalose-6-phosphate synthase/phosphatase
      (OtsA-OtsB) pathway, and the trehalose synthase (TreS) pathway. The former was
      used for trehalose synthesis, whereas the latter is proposed to operate in
      trehalose degradation. The activities of OtsA, OtsB and TreS were detected in
      cell extracts; the corresponding genes were identified, and the recombinant
      proteins were characterized in detail. In crude extracts of P. freudenreichii,
      OtsA was specific for ADP-glucose, in contrast to the pure recombinant OtsA,
      which used UDP-, GDP- and TDP-glucose, in addition to ADP-glucose. Moreover, the
      substrate specificity of OtsA in cell extracts was lost during purification, and
      the recombinant OtsA became specific to ADP-glucose upon incubation with a
      dialysed cell extract. The level of OtsA was enhanced (approximately twofold) by
      osmotic, oxidative and acid stress, whereas the level of TreS remained constant,
      or it decreased, under identical stress conditions. Therefore, the OtsA-OtsB
      pathway plays an important role in the synthesis of trehalose in response to
      stress. It is most likely that trehalose degradation proceeds via TreS to yield
      maltose, which is subsequently catabolized via amylomaltase activity. Hydrolytic
      activities that are potentially involved in trehalose degradation (trehalase,
      trehalose phosphorylase, trehalose-6-phosphate phosphorylase and trehalose-6
      phosphate hydrolase) were not present. The role of trehalose as a common response
      to three distinct stresses is discussed.

PMID- 17185555
TI  - Role of the alternative sigma factors sigmaE and sigmaS in survival of Salmonella
      enterica serovar Typhimurium during starvation, refrigeration and osmotic shock.
AB  - The ability of Salmonella enterica serovar Typhimurium to survive environmental
      stress requires specific, coordinated, responses, which induce resistance to the
      stress condition. This study investigated the relative contribution of sigmaE and
      sigmaS, the sigma factors regulating extracytoplasmic and general stress response
      functions, respectively, to survival at low temperature and also in media of
      differing osmotic strength, conditions relevant to food preservation. To
      determine if low-temperature storage is a signal for sigmaE- and sigmaS-mediated
      survival, the ability of S. Typhimurium rpoE, rpoS and rpoE/rpoS mutants to
      survive in a saline starvation-survival model at a refrigeration temperature (4.5
      degrees C) was examined. Under these conditions, the rpoE mutant was
      significantly (P<0.05) compromised compared to the parent and to an rpoS mutant.
      The double mutant in rpoE and rpoS displayed a cumulative defect in survival. In
      hyperosmotic environments (low aw) containing 6 % NaCl and at refrigeration
      temperature, both sigma factors were important for maximum survival but sigmaS
      played the dominant role. Analysis of the metabolic activity of starved
      populations at 4.5 and 37 degrees C revealed significantly (P<0.001) elevated
      electron-transport system activity in mutants in rpoE and rpoS, indicating a role
      for sigmaE- and sigmaS-regulated genes in maintaining energy homeostasis.
      Together these data demonstrate that sigmaE and sigmaS are important for survival
      of S. Typhimurium in conditions encountered during food processing and that the
      relative contribution of sigmaE and sigmaS is critically dependent on the precise
      nature of the stress.

PMID- 17185557
TI  - Metabolic flux profiling of Pichia pastoris grown on glycerol/methanol mixtures
      in chemostat cultures at low and high dilution rates.
AB  - The metabolic pathways associated with the tricarboxylic acid cycle intermediates
      of Pichia pastoris were studied using biosynthetically directed fractional 13C
      labelling. Cells were grown aerobically in a chemostat culture fed at two
      dilution rates (1.39x10(-5) s-1 and 4.44x10(-5) s-1) with varying mixtures of
      glycerol and methanol as sole carbon sources. The results show that, with co
      assimilation of methanol, the common amino acids are synthesized as in P.
      pastoris cells grown on glycerol only. During growth at the lower dilution rate,
      when both substrates are entirely consumed, the incorporation of methanol into
      the biomass increases as the methanol fraction in the feed is increased.
      Moreover, the co-assimilation of methanol impacts on how key intermediates of the
      pentose phosphate pathway (PPP) are synthesized. In contrast, such an impact on
      the PPP is not observed at the higher dilution rate, where methanol is only
      partially consumed. This finding possibly indicates that the distribution of
      methanol carbon into assimilatory and dissimilatory (direct oxidation to CO2)
      pathways are different at the two dilution rates. Remarkably, distinct flux
      ratios were registered at each of the two growth rates, while the dependency of
      the flux ratios on the varying fraction of methanol in the medium was much less
      pronounced. This study brings new insights into the complex regulation of P.
      pastoris methanol metabolism in the presence of a second carbon source, revealing
      important implications for biotechnological applications.

PMID- 17185558
TI  - Growth of probiotic lactobacilli in the presence of oleic acid enhances
      subsequent survival in gastric juice.
AB  - The effect of inclusion of various C18 fatty acids with 0-2 double bonds in
      either cis or trans configuration on Lactobacillus rhamnosus GG survival was
      analysed in simulated gastric juice at pH 2.5. The incorporation of Tween 80 (1 g
      l-1) in the growth media enhanced subsequent survival of stationary-phase
      cultures up to 1000-fold following 90 min acid exposure compared with controls
      grown without Tween 80. There was a significant (P<0.05) increase in bacterial
      content of oleic acid [C18:1 (9c), up to 55-fold] after growth of bacteria in MRS
      supplemented with Tween 80. The inclusion of various C18 fatty acids in the
      growth media revealed that only oleic and vaccenic acids [C18:1 (11t)] had
      protective effects on the survival of Lb. rhamnosus GG when exposed to the acidic
      environment. Comparative analysis with other lactobacilli indicated that all
      strains exhibited increased survival when grown in the presence of Tween 80.
      Further work with a neomycin-resistant mutant with 48% of the F0F1-ATPase
      activity of the parent indicated that the Tween 80 effect was independent of the
      complex. The mechanisms behind the effect of fatty acid protection were
      investigated and proton permeability assays showed that cultures grown in the
      presence of Tween 80 had higher extracellular pH than controls. Furthermore,
      there was a significant reduction of oleic acid and a significant increase in
      stearic acid (C18:0) (P<0.05) content of bacterial cells following exposure of
      Tween 80-supplemented cultures to simulated gastric juice. Overall, the data
      suggest that probiotic lactobacilli can use an exogenous oleic acid source to
      increase their acid survival and the underlying mechanism most likely involves
      the ability of increased membrane oleic acid to be reduced by H+ to stearic acid.

PMID- 17185559
TI  - Genetics. SNPs, silent but not invisible.

PMID- 17185560
TI  - A "silent" polymorphism in the MDR1 gene changes substrate specificity.
AB  - Synonymous single-nucleotide polymorphisms (SNPs) do not produce altered coding
      sequences, and therefore they are not expected to change the function of the
      protein in which they occur. We report that a synonymous SNP in the Multidrug
      Resistance 1 (MDR1) gene, part of a haplotype previously linked to altered
      function of the MDR1 gene product P-glycoprotein (P-gp), nonetheless results in P
      gp with altered drug and inhibitor interactions. Similar mRNA and protein levels,
      but altered conformations, were found for wild-type and polymorphic P-gp. We
      hypothesize that the presence of a rare codon, marked by the synonymous
      polymorphism, affects the timing of cotranslational folding and insertion of P-gp
      into the membrane, thereby altering the structure of substrate and inhibitor
      interaction sites.

PMID- 17185561
TI  - Chemical and spectroscopic evidence for an FeV-oxo complex.
AB  - Iron(V)-oxo species have been proposed as key reactive intermediates in the
      catalysis of oxygen-activating enzymes and synthetic catalysts. Here, we report
      the synthesis of [Fe(TAML)(O)]- in nearly quantitative yield, where TAML is a
      macrocyclic tetraamide ligand. Mass spectrometry, Mossbauer, electron
      paramagnetic resonance, and x-ray absorption spectroscopies, as well as
      reactivity studies and density functional theory calculations show that this long
      lived (hours at -60 degrees C) intermediate is a spin S = 1/2 iron(V)-oxo
      complex. Iron-TAML systems have proven to be efficient catalysts in the
      decomposition of numerous pollutants by hydrogen peroxide, and the species we
      characterized is a likely reactive intermediate in these reactions.

PMID- 17185562
TI  - Imaging of germinal center selection events during affinity maturation.
AB  - The germinal center (GC) is an important site for the generation and selection of
      B cells bearing high-affinity antibodies, yet GC cell migration and interaction
      dynamics have not been directly observed. Using two-photon microscopy of mouse
      lymph nodes, we revealed that GC B cells are highly motile and extend long cell
      processes. They transited between GC dark and light zones and divided in both
      regions, although these B cells resided for only several hours in the light zone
      where antigen is displayed. GC B cells formed few stable contacts with GC T cells
      despite frequent encounters, and T cells were seen to carry dead B cell blebs. On
      the basis of these observations, we propose a model in which competition for T
      cell help plays a more dominant role in the selection of GC B cells than
      previously appreciated.

PMID- 17185564
TI  - Breakthrough of the year.

PMID- 17185565
TI  - Breakthrough of the year. The Poincare conjecture--proved.

PMID- 17185563
TI  - Nuclear activity of MLA immune receptors links isolate-specific and basal disease
      resistance responses.
AB  - Plant immune responses are triggered by pattern recognition receptors that detect
      conserved pathogen-associated molecular patterns (PAMPs) or by resistance (R)
      proteins recognizing isolate-specific pathogen effectors. We show that in barley,
      intracellular mildew A (MLA) R proteins function in the nucleus to confer
      resistance against the powdery mildew fungus. Recognition of the fungal
      avirulence A10 effector by MLA10 induces nuclear associations between receptor
      and WRKY transcription factors. The identified WRKY proteins act as repressors of
      PAMP-triggered basal defense. MLA appears to interfere with the WRKY repressor
      function, thereby de-repressing PAMP-triggered basal defense. Our findings reveal
      a mechanism by which these polymorphic immune receptors integrate distinct
      pathogen signals.

PMID- 17185566
TI  - Breakthrough of the year. The runners-up.

PMID- 17185567
TI  - Breakthrough of the year. Scorecard 2006.

PMID- 17185568
TI  - Breakthrough of the year. Breakdown of the year: scientific fraud.

PMID- 17185569
TI  - Breakthrough of the year. Areas to watch in 2007.

PMID- 17185570
TI  - Scientific publishing. A scientist's nightmare: software problem leads to five
      retractions.

PMID- 17185571
TI  - U.S. ocean policy. Fisheries bill gives bigger role to science--but no money.

PMID- 17185572
TI  - Immunology. Mouse studies question importance of toll-like receptors to vaccines.

PMID- 17185573
TI  - Wildlife conservation. River dolphins down for the count, and perhaps out.

PMID- 17185575
TI  - Archaeology. Researchers helpless as Bosnian pyramid bandwagon gathers pace.

PMID- 17185574
TI  - Environment. Spain's prestige oil spill resurfaces.

PMID- 17185576
TI  - 2007 U.S. budget. NIH trims award size as spending crunch looms.

PMID- 17185577
TI  - Nonproliferation. Indo-U.S. nuclear pact in jeopardy.

PMID- 17185578
TI  - American Society for Cell Biology meeting. A gut germ goes AWOL.

PMID- 17185579
TI  - American Society for Cell Biology. Sprayed-on growth factors guide stem cells.

PMID- 17185580
TI  - Scientific publishing. Don't pretty up that picture just yet.

PMID- 17185581
TI  - Data storage. Is the terabit within reach?

PMID- 17185582
TI  - Bruce Lahn profile. Brain man makes waves with claims of recent human evolution.

PMID- 17185583
TI  - Bruce Lahn profile. Links between brain genes, evolution, and cognition
      challenged.

PMID- 17185584
TI  - Retraction.

PMID- 17185585
TI  - Aquaculture in offshore zones.

PMID- 17185586
TI  - Inquiry learning. Teaching scientific inquiry.

PMID- 17185587
TI  - Biochemistry. Proteins in a small world.

PMID- 17185588
TI  - Evolution. The origin of insects.

PMID- 17185589
TI  - Epidemiology. Influenza escapes immunity along neutral networks.

PMID- 17185590
TI  - Biochemistry. If the RNA fits, use it.

PMID- 17185591
TI  - Earth science. A submarine volcano is caught in the act.

PMID- 17185592
TI  - Physics. Gaps and our understanding.

PMID- 17185593
TI  - Ancient noncoding elements conserved in the human genome.
AB  - Cartilaginous fishes represent the living group of jawed vertebrates that
      diverged from the common ancestor of human and teleost fish lineages about 530
      million years ago. We generated approximately 1.4x genome sequence coverage for a
      cartilaginous fish, the elephant shark (Callorhinchus milii), and compared this
      genome with the human genome to identify conserved noncoding elements (CNEs). The
      elephant shark sequence revealed twice as many CNEs as were identified by whole
      genome comparisons between teleost fishes and human. The ancient vertebrate
      specific CNEs in the elephant shark and human genomes are likely to play key
      regulatory roles in vertebrate gene expression.

PMID- 17185594
TI  - Untemplated oligoadenylation promotes degradation of RISC-cleaved transcripts.
AB  - Double-stranded RNA, processed to small interfering RNAs (siRNAs) by Dicer and
      incorporated into the RNA-induced silencing complex (RISC), triggers gene
      silencing by a variety of pathways in eukaryotes. RNA interference involving the
      degradation of homologous transcripts is the best-characterized mechanism.
      However, the fate of the RNA fragments resulting from siRNA-directed cleavage is
      poorly understood. We have identified a gene (MUT68) in the unicellular green
      alga Chlamydomonas reinhardtii that is required for the efficient decay of siRNA
      targeted transcripts. MUT68 encodes a noncanonical polyadenylate polymerase that
      adds untemplated adenines to the 5' RNA fragments after siRNA-mediated cleavage
      and appears to stimulate their exosome-dependent degradation.

PMID- 17185595
TI  - The heartbeat of the Oligocene climate system.
AB  - A 13-million-year continuous record of Oligocene climate from the equatorial
      Pacific reveals a pronounced "heartbeat" in the global carbon cycle and
      periodicity of glaciations. This heartbeat consists of 405,000-, 127,000-, and
      96,000-year eccentricity cycles and 1.2-million-year obliquity cycles in
      periodically recurring glacial and carbon cycle events. That climate system
      response to intricate orbital variations suggests a fundamental interaction of
      the carbon cycle, solar forcing, and glacial events. Box modeling shows that the
      interaction of the carbon cycle and solar forcing modulates deep ocean acidity as
      well as the production and burial of global biomass. The pronounced 405,000-year
      eccentricity cycle is amplified by the long residence time of carbon in the
      oceans.

PMID- 17185598
TI  - A gaseous metal disk around a white dwarf.
AB  - The destiny of planetary systems through the late evolution of their host stars
      is very uncertain. We report a metal-rich gas disk around a moderately hot and
      young white dwarf. A dynamical model of the double-peaked emission lines
      constrains the outer disk radius to just 1.2 solar radii. The likely origin of
      the disk is a tidally disrupted asteroid, which has been destabilized from its
      initial orbit at a distance of more than 1000 solar radii by the interaction with
      a relatively massive planetesimal object or a planet. The white dwarf mass of
      0.77 solar mass implies that planetary systems may form around high-mass stars.

PMID- 17185597
TI  - Structure of dual function iron regulatory protein 1 complexed with ferritin IRE
      RNA.
AB  - Iron regulatory protein 1 (IRP1) binds iron-responsive elements (IREs) in
      messenger RNAs (mRNAs), to repress translation or degradation, or binds an iron
      sulfur cluster, to become a cytosolic aconitase enzyme. The 2.8 angstrom
      resolution crystal structure of the IRP1:ferritin H IRE complex shows an open
      protein conformation compared with that of cytosolic aconitase. The extended, L
      shaped IRP1 molecule embraces the IRE stem-loop through interactions at two sites
      separated by approximately 30 angstroms, each involving about a dozen protein:RNA
      bonds. Extensive conformational changes related to binding the IRE or an iron
      sulfur cluster explain the alternate functions of IRP1 as an mRNA regulator or
      enzyme.

PMID- 17185596
TI  - Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in
      humans.
AB  - Human influenza A (subtype H3N2) is characterized genetically by the limited
      standing diversity of its hemagglutinin and antigenically by clusters that emerge
      and replace each other within 2 to 8 years. By introducing an epidemiological
      model that allows for differences between the genetic and antigenic properties of
      the virus's hemagglutinin, we show that these patterns can arise from cluster
      specific immunity alone. Central to the formulation is a genotype-to-phenotype
      mapping, based on neutral networks, with antigenic phenotypes, not genotypes,
      determining the degree of strain cross-immunity. The model parsimoniously
      explains well-known, as well as previously unremarked, features of interpandemic
      influenza dynamics and evolution. It captures the observed boom-and-bust pattern
      of viral evolution, with periods of antigenic stasis during which genetic
      diversity grows, and with episodic contraction of this diversity during cluster
      transitions.

PMID- 17185599
TI  - A giant European dinosaur and a new sauropod clade.
AB  - Fossils of a giant sauropod dinosaur, Turiasaurus riodevensis, have been
      recovered from terrestrial deposits of the Villar del Arzobispo Formation
      (Jurassic-Cretaceous boundary) of Riodeva (Teruel Province, Spain). Its humerus
      length (1790 millimeters) and estimated mass (40 to 48 metric tons) indicate that
      it may have been the most massive terrestrial animal in Europe and one of the
      largest in the world. Phylogenetic analysis indicates that the fossil represents
      a member of a hitherto unrecognized group of primitive European eusauropods that
      evolved in the Jurassic.

PMID- 17185600
TI  - Anticipatory reproduction and population growth in seed predators.
AB  - Mast seeding, the intermittent, synchronous production of large seed crops by a
      population of plants, is a well-known example of resource pulses that create
      lagged responses in successive trophic levels of ecological communities. These
      lags arise because seed predators are thought capable of increasing reproduction
      and population size only after the resource pulse is available for consumption.
      The resulting satiation of predators is a widely cited explanation for the
      evolution of masting. Our study shows that both American and Eurasian tree
      squirrels anticipate resource pulses and increase reproductive output before a
      masting event, thereby increasing population size in synchrony with the resource
      pulse and eliminating the population lag thought to be universal in resource
      pulse systems.

PMID- 17185601
TI  - Human catechol-O-methyltransferase haplotypes modulate protein expression by
      altering mRNA secondary structure.
AB  - Catechol-O-methyltransferase (COMT) is a key regulator of pain perception,
      cognitive function, and affective mood. Three common haplotypes of the human COMT
      gene, divergent in two synonymous and one nonsynonymous position, code for
      differences in COMT enzymatic activity and are associated with pain sensitivity.
      Haplotypes divergent in synonymous changes exhibited the largest difference in
      COMT enzymatic activity, due to a reduced amount of translated protein. The major
      COMT haplotypes varied with respect to messenger RNA local stem-loop structures,
      such that the most stable structure was associated with the lowest protein levels
      and enzymatic activity. Site-directed mutagenesis that eliminated the stable
      structure restored the amount of translated protein. These data highlight the
      functional significance of synonymous variations and suggest the importance of
      haplotypes over single-nucleotide polymorphisms for analysis of genetic
      variations.

PMID- 17185602
TI  - Lineages of acidophilic archaea revealed by community genomic analysis.
AB  - Novel, low-abundance microbial species can be easily overlooked in standard
      polymerase chain reaction (PCR)-based surveys. We used community genomic data
      obtained without PCR or cultivation to reconstruct DNA fragments bearing unusual
      16S ribosomal RNA (rRNA) and protein-coding genes from organisms belonging to
      novel archaeal lineages. The organisms are minor components of all biofilms
      growing in pH 0.5 to 1.5 solutions within the Richmond Mine, California. Probes
      specific for 16S rRNA showed that the fraction less than 0.45 micrometers in
      diameter is dominated by these organisms. Transmission electron microscope images
      revealed that the cells are pleomorphic with unusual folded membrane protrusions
      and have apparent volumes of <0.006 cubic micrometer.

PMID- 17185604
TI  - Relating three-dimensional structures to protein networks provides evolutionary
      insights.
AB  - Most studies of protein networks operate on a high level of abstraction,
      neglecting structural and chemical aspects of each interaction. Here, we
      characterize interactions by using atomic-resolution information from three
      dimensional protein structures. We find that some previously recognized
      relationships between network topology and genomic features (e.g., hubs tending
      to be essential proteins) are actually more reflective of a structural quantity,
      the number of distinct binding interfaces. Subdividing hubs with respect to this
      quantity provides insight into their evolutionary rate and indicates that
      additional mechanisms of network growth are active in evolution (beyond effective
      preferential attachment through gene duplication).

PMID- 17185603
TI  - Adjuvant-enhanced antibody responses in the absence of toll-like receptor
      signaling.
AB  - Innate immune signals mediated by Toll-like receptors (TLRs) have been thought to
      contribute considerably to the antibody-enhancing effects of vaccine adjuvants.
      However, we report here that mice deficient in the critical signaling components
      for TLR mount robust antibody responses to T cell-dependent antigen given in four
      typical adjuvants: alum, Freund's complete adjuvant, Freund's incomplete
      adjuvant, and monophosphoryl-lipid A/trehalose dicorynomycolate adjuvant. We
      conclude that TLR signaling does not account for the action of classical
      adjuvants and does not fully explain the action of a strong adjuvant containing a
      TLR ligand. This may have important implications in the use and development of
      vaccine adjuvants.

PMID- 17185605
TI  - Characterizing a mammalian circannual pacemaker.
AB  - Many species express endogenous cycles in physiology and behavior that allow
      anticipation of the seasons. The anatomical and cellular bases of these
      circannual rhythms have not been defined. Here, we provide strong evidence using
      an in vivo Soay sheep model that the circannual regulation of prolactin
      secretion, and its associated biology, derive from a pituitary-based timing
      mechanism. Circannual rhythm generation is seen as the product of the interaction
      between melatonin-regulated timer cells and adjacent prolactin-secreting cells,
      which together function as an intrapituitary "pacemaker-slave" timer system.
      These new insights open the way for a molecular analysis of long-term timing
      mechanisms.

PMID- 17185606
TI  - Widespread distribution and muscle differentiation of human fetal mesenchymal
      stem cells after intrauterine transplantation in dystrophic mdx mouse.
AB  - Duchenne muscular dystrophy (DMD) is a common X-linked disease resulting from the
      absence of dystrophin in muscle. Affected boys suffer from incurable progressive
      muscle weakness, leading to premature death. Stem cell transplantation may be
      curative, but is hampered by the need for systemic delivery and immune rejection.
      To address these barriers to stem cell therapy in DMD, we investigated a fetal-to
      fetal transplantation strategy. We investigated intramuscular, intravascular, and
      intraperitoneal delivery of human fetal mesenchymal stem cells (hfMSCs) into
      embryonic day (E) 14-16 MF1 mice to determine the most appropriate route for
      systemic delivery. Intramuscular injections resulted in local engraftment,
      whereas both intraperitoneal and intravascular delivery led to systemic spread.
      However, intravascular delivery led to unexpected demise of transplanted mice.
      Transplantation of hfMSCs into E14-16 mdx mice resulted in widespread long-term
      engraftment (19 weeks) in multiple organs, with a predilection for muscle
      compared with nonmuscle tissues (0.71% vs. 0.15%, p < .01), and evidence of
      myogenic differentiation of hfMSCs in skeletal and myocardial muscle. This is the
      first report of intrauterine transplantation of ontologically relevant hfMSCs
      into fully immunocompetent dystrophic fetal mice, with systemic spread across
      endothelial barriers leading to widespread long-term engraftment in multiple
      organ compartments. Although the low-level of chimerism achieved is not curative
      for DMD, this approach may be useful in other severe mesenchymal or enzyme
      deficiency syndromes, where low-level protein expression may ameliorate disease
      pathology.

PMID- 17185607
TI  - Spontaneous fusion and nonclonal growth of adult neural stem cells.
AB  - Multipotent neural stem cells (NSCs) can be isolated from various regions of the
      adult brain and propagated in vitro. Recent reports have suggested spontaneous
      fusion events among NSCs when grown as free-floating neurospheres that may affect
      the genetic composition of NSC cultures. We used adult NSCs expressing either red
      fluorescent protein (RFP) or green fluorescent protein (GFP) to analyze the
      fusion frequency of rat and mouse NSCs. Fluorescence-activated cell sorting
      (FACS) revealed that, under proliferating conditions, approximately 0.2% of rat
      and mouse NSCs coexpressed RFP and GFP irrespective of whether the cells were
      grown as neurospheres (mouse NSCs) or as attached monolayers (rat and mouse
      NSCs). Fused cells did not proliferate and could not be propagated, suggesting
      that aberrantly fused cells are not viable. Furthermore, we found that neither
      neurospheres nor monolayers grew clonally, because even very low-density cultures
      had spheres containing both GFP- and RFP-expressing cells and monolayer patches
      with GFP- and RFP-expressing cells in close proximity. The nonclonal growth
      between distinct NSC populations strongly suggests the use of careful and precise
      culture conditions, such as single-cell assays, to characterize potency and
      growth of NSCs in vitro.

PMID- 17185608
TI  - Efficient establishment of mouse embryonic stem cell lines from single
      blastomeres and polar bodies.
AB  - Recently, ES cell lines were established from single blastomeres taken from eight
      cell embryos in mice and humans with success rates of 4% and 2%, respectively,
      which suggests that the method could be used in regenerative medicine to reduce
      ethical concerns over harm to embryos. However, those studies used other ES cells
      as supporting cells. Here, we report a simple and highly efficient method of
      establishing mouse ES cell lines from single blastomeres, in which single
      blastomeres are simply plated onto a feeder layer of mouse embryonic fibroblasts
      with modified ES cell medium. A total of 112 ES cell lines were established from
      two-cell (establishment rate, 50%-69%), early four-cell (28%-40%), late four-cell
      (22%), and eight-cell (14%-16%) stage embryos. We also successfully established
      18 parthenogenetic ES cell lines from first (36%-40%) and second polar bodies
      (33%), the nuclei of which were reconstructed to embryos by nuclear transfer.
      Most cell lines examined maintained normal karyotypes and expressed markers of
      pluripotency, including germline transmission in chimeric mice. Our results
      suggest that the single cells of all early-stage embryos or polar bodies have the
      potential to be converted into ES cells without any special treatment.

PMID- 17185609
TI  - Improved human embryonic stem cell embryoid body homogeneity and cardiomyocyte
      differentiation from a novel V-96 plate aggregation system highlights interline
      variability.
AB  - Although all human ESC (hESC) lines have similar morphology, express key
      pluripotency markers, and can differentiate toward primitive germ layers in
      vitro, the lineage-specific developmental potential may vary between individual
      lines. In the current study, four hESC lines were cultured in the same feeder
      free conditions to provide a standardized platform for interline analysis. A high
      throughput, forced-aggregation system involving centrifugation of defined numbers
      of hESCs in V-96 plates (V-96FA) was developed to examine formation, growth, and
      subsequent cardiomyocyte differentiation from >22,000 EBs. Homogeneity of EBs
      formed by V-96FA in mouse embryo fibroblast-conditioned medium was significantly
      improved compared with formation in mass culture (p < .02; Levene's test). V-96FA
      EB formation was successful in all four lines, although significant differences
      in EB growth were observed during the first 6 days of differentiation (p = .044
      to .001; one-way analysis of variance [ANOVA]). Cardiomyocyte differentiation
      potential also varied; 9.5% +/- 0.9%, 6.6% +/- 2.4%, 5.2% +/- 3.1%, and 1.6% +/-
      1.0% beating EBs were identified for HUES-7, NOTT2, NOTT1, and BG01, respectively
      (p = .008; one-way ANOVA). Formation of HUES-7 V-96FA EBs in defined medium
      containing activin A and basic fibroblast growth factor resulted in 23.6% +/-
      3.6% beating EBs, representing a 13.1-fold increase relative to mass culture
      (1.8% +/- 0.7%), consistent with an observed 14.8-fold increase in MYH6
      (alphaMHC) expression by real-time polymerase chain reaction. In contrast, no
      beating areas were derived from NOTT1-EBs and BG01-EBs formed in defined medium.
      Thus, the V-96FA system highlighted interline variability in EB growth and
      cardiomyocyte differentiation but, under the test conditions described,
      identified HUES-7 as a line that can respond to cardiomyogenic stimulation.

PMID- 17185610
TI  - Side population analysis using a violet-excited cell-permeable DNA binding dye.
AB  - Hoechst 33342 side population (SP) analysis is a common method for identifying
      stem cells in mammalian hematopoietic and nonhematopoietic tissues. Although
      widely employed for stem cell analysis, this method requires an ultraviolet (UV)
      laser to excite Hoechst 33342. Flow cytometers equipped with UV sources are not
      common because of the cost of both the laser and optics that can transmit light
      UV light. Violet laser sources are inexpensive and are now common fixtures on
      flow cytometers, but have been previously shown to provide insufficient Hoechst
      dye excitation for consistent resolution of SP cells. One solution to this
      problem is to identify additional fluorescent substrates with the same pump
      specificity as Hoechst 33342, but with better violet excitation characteristics.
      DyeCycle Violet reagent has emission characteristics similar to those of Hoechst
      33342, but with a longer wavelength excitation maxima (369 nm). When this dye is
      loaded into hematopoietic cells, a sharply resolved side population was also
      observed, similar in appearance to that seen with Hoechst 33342. Unlike Hoechst
      SP, DCV SP was similar in appearance with both violet and UV excitation. DCV SP
      could be inhibited fumitremorgin C, and showed the same membrane pump specificity
      as Hoechst 33342. Simultaneous immunophenotyping with stem cell markers in mouse
      bone marrow demonstrated that DCV SP was restricted to the stem cell lineage(-)
      Sca-1(+) c-kit(+) cells population, as is Hoechst SP. Pending confirmation by
      functional analysis of DCV SP cells, these results suggest that DCV efflux
      identified approximately the same stem cell population as did Hoechst 33342
      efflux. Substituting DCV for Hoechst 33342 in the SP technique may, therefore,
      allow side population analysis on flow cytometers with violet lasers.

PMID- 17185611
TI  - Human leukocyte antigen matching estimations in a hypothetical bank of human
      embryonic stem cell lines in the Japanese population for use in cell
      transplantation therapy.
AB  - Human embryonic stem (hES) cell lines are of great potential in cell
      transplantation therapy. However, recipients of such allogeneic transplants
      probably need treatment with immunosuppressants. Recently, Taylor et al. [Lancet
      2005;366:2019-2025] proposed banking of hES cell lines and estimated the required
      number of hES cell lines for beneficial human leukocyte antigen (HLA) matching in
      the U.K. population. Here, we carried out such an estimation in the Japanese
      population. We calculated the proportion of patients who can find at least one
      HLA-matched donor at three loci of HLA-A, -B, and -DR. With a bank of hES cell
      lines from 170 randomly selected donated embryos, 80% of patients were expected
      to find at least one hES cell line with a single mismatch at one HLA locus or a
      better match. Furthermore, 80% of patients are expected to find at least one
      donor with complete matching at the three HLA loci if parthenogenetic homozygous
      hES cell lines are established from 55 randomly selected donated oocytes. The
      relatively low ethnic diversity of the Japanese population may have resulted in a
      high success rate in beneficial matching. Moreover, parthenogenetic hES cell
      lines can greatly reduce the number required for a higher degree of HLA matching.

PMID- 17185612
TI  - Transcriptional profiling of human cord blood CD133+ and cultured bone marrow
      mesenchymal stem cells in response to hypoxia.
AB  - Umbilical cord blood (UCB) and bone marrow (BM)-derived stem and progenitor cells
      possess two characteristics required for successful tissue regeneration:
      extensive proliferative capacity and the ability to differentiate into multiple
      cell lineages. Within the normal BM and in pathological conditions, areas of
      hypoxia may have a role in maintaining stem cell fate or determining the fine
      equilibrium between their proliferation and differentiation. In this study, the
      transcriptional profiles and proliferation and differentiation potential of UCB
      CD133(+) cells and BM mesenchymal cells (BMMC) exposed to normoxia and hypoxia
      were analyzed and compared. Both progenitor cell populations responded to hypoxic
      stimuli by stabilizing the hypoxia inducible factor (HIF)-1alpha protein. Short
      exposures to hypoxia increased the clonogenic myeloid capacity of UCB CD133(+)
      cells and promoted a significant increase in BMMC number. The differentiation
      potential of UCB CD133(+) clonogenic myeloid cells was unaltered by short
      exposures to hypoxia. In contrast, the chondrogenic differentiation potential of
      BMMCs was enhanced by hypoxia, whereas adipogenesis and osteogenesis were
      unaltered. When their transcriptional profiles were compared, 183 genes in UCB
      CD133(+) cells and 45 genes in BMMC were differentially regulated by hypoxia.
      These genes included known hypoxia-responsive targets such as BNIP3, PGK1, ENO2,
      and VEGFA, and other genes not previously described to be regulated by hypoxia.
      Several of these genes, namely CDTSPL, CCL20, LSP1, NEDD9, TMEM45A, EDG-1, and
      EPHA3 were confirmed to be regulated by hypoxia using quantitative reverse
      transcriptase polymerase chain reaction. These results, therefore, provide a
      global view of the signaling and regulatory network that controls oxygen sensing
      in human adult stem/progenitor cells derived from hematopoietic tissues.

PMID- 17185613
TI  - Potential of CD34 in the regulation of symmetrical and asymmetrical divisions by
      hematopoietic progenitor cells.
AB  - The control of symmetric and asymmetric division in the hematopoietic
      stem/progenitor cell population is critically important for the regulation of
      blood cell production. Asymmetric divisions depend on cell polarization, which
      may be conferred by location and/or interaction with neighboring cells. In this
      study, we sought evidence for polarization in CD34+ cells, which interact by
      binding to one another. In these cells, surface molecules became redistributed by
      mechanisms that included transport by lipid rafts, and the interacting cells were
      able to communicate via gap junctions. These changes were accompanied by
      modulation of cell cycle regulating proteins (p16(Ink4a), p27(kip1), cyclins D,
      and the retinoblastoma pathway proteins) and a reduction in progenitor cell
      proliferation in vitro. These results are consistent with an increase in
      asymmetric cell division kinetics. Accordingly, we found that interaction between
      CD34+ cells influenced the plane of cell division in a way that suggests unequal
      sharing of Notch-1 between daughter cell progeny. We conclude that interaction
      between CD34+ cells may coordinate cell function and participate in the control
      of hematopoietic stem/progenitor cell division kinetics.

PMID- 17185614
TI  - Tetradecylselenoacetic acid, a PPAR ligand with antioxidant, antiinflammatory,
      and hypolipidemic properties.
AB  - OBJECTIVE: Antioxidants protect against oxidative stress and inflammation, which,
      in combination with hyperlipidemia, are important mediators of atherogenesis.
      Here we present a selenium-substituted fatty acid, tetradecylselenoacetic acid
      (TSA), which is hypothesized to have antioxidant, antiinflammatory, and
      hypolipidemic properties. METHODS AND RESULTS: We show that TSA exerts
      antioxidant properties by delaying the onset of oxidation of human low density
      lipoprotein (LDL), by reducing the uptake of oxidized LDL in murine macrophages,
      and by increasing the mRNA level of superoxide dismutase in rat liver. TSA also
      showed antiinflammatory effects by suppressing the release of interleukin (IL)-2
      and -4, and by increasing the release of IL-10 in human blood leukocytes. In
      addition, TSA decreased the plasma triacylglycerol level and increased the
      mitochondrial fatty acid beta-oxidation in rat liver. In pigs, TSA seemed to
      reduce coronary artery intimal thickening after percutaneous coronary
      intervention. In HepG2 cells TSA activated all peroxisome proliferator-activated
      receptors (PPARs) in a dose-dependent manner. CONCLUSIONS: Our data suggest that
      TSA exert potent antioxidant, antiinflammatory, and hypolipidemic properties,
      potentially involving PPAR-related mechanisms. Based on these effects, it is
      tempting to hypothesize that TSA could be an interesting antiatherogenic approach
      to atherosclerotic disorders.

PMID- 17185615
TI  - Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase blunts
      factor VIIa/tissue factor and prothrombinase activities via effects on membrane
      phosphatidylserine.
AB  - OBJECTIVE: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors
      (statins) exhibit antithrombotic properties that are independent of reductions in
      circulating LDL cholesterol. We hypothesized that these antithrombotic properties
      are mediated by membrane alterations secondary to disrupted lipid metabolism.
      METHODS AND RESULTS: EA.hy926 cells were incubated in the presence of 1
      micromol/L atorvastatin supplemented with fetal bovine serum or lipid-depleted
      serum mixtures. Lipid restriction alone had no effect on cell lipid composition
      but when atorvastatin was included, phosphatidylserine, sphingomyelin, and
      cholesterol were reduced by 50% while ceramide content decreased by 70%. These
      changes in lipid composition did not alter the association of decay accelerating
      factor or tissue factor with lipid rafts. Atorvastatin in combination with lipid
      restriction reduced factor VIIa/tissue factor activity by as much as 75% but did
      not alter tissue factor expression. Prothrombinase activity was reduced to an
      extent similar to factor VIIa/tissue factor. Mevalonic acid but not LDL reversed
      the observed changes in lipid content and prothrombinase activity induced by
      atorvastatin. These findings were confirmed in primary cells. CONCLUSIONS:
      Inhibition of HMG-CoA reductase limits exposure of phosphatidylserine at the cell
      surface by restricting the cellular pool of mevalonate-derived isoprenoids. This
      membrane alteration restricts the activity of proteolytic enzyme complexes that
      propagate the coagulation cascade.

PMID- 17185616
TI  - Functional arterial and venous fate is determined by graded VEGF signaling and
      notch status during embryonic stem cell differentiation.
AB  - OBJECTIVE: The aim of this work was to develop a mouse embryonic stem (ES) cell
      system addressing the early specification of the developing vasculature into
      functional arteries and veins. METHODS AND RESULTS: ES cells were differentiated
      4 days on collagen-type IV coated dishes to obtain Flk1+ endothelial precursors.
      Sub-culture of these precursors for additional 4 days robustly generated, in a
      VEGF dose-dependent manner, mature endothelial cells. Arterial marker genes were
      specifically expressed in cultures differentiated with high VEGF concentration
      whereas the venous marker gene COUP-TFII was upregulated in endothelial cells
      induced through low and intermediate VEGF concentrations. This VEGF-dependent
      arterialization could be blocked by inhibition of Notch resulting in an arterial
      to venous fate switch. Functional and morphological studies, ie, measurement of
      sprout length, pericyte recruitment, and interleukin-I-induced leukocyte
      adhesion, further confirmed their arterial and venous identity. CONCLUSIONS: We
      conclude that endothelial cells with distinct molecular, morphological, and
      functional characteristics of arteries and veins can be derived through in vitro
      differentiation of ES cells in a VEGF dose-dependent and Notch-regulated manner.

PMID- 17185620
TI  - Gamma-glutamyl transferase: another biomarker for metabolic syndrome and
      cardiovascular risk.

PMID- 17185617
TI  - Aortic valve calcification: determinants and progression in the population.
AB  - BACKGROUND: Aortic valve calcification (AVC) is considered degenerative. Recent
      data suggested links to atherosclerosis or coronary disease (CAD). METHODS AND
      RESULTS: AVC and coronary artery calcifications (CAC) were prospectively assessed
      by Electron-Beam-Computed-Tomography in 262 population-based research
      participants > or = 60 years. AVC was frequent (27%) with aging (P<0.01) and in
      men (P<0.05). AVC was associated with diabetes, hypertension, higher body-mass
      index, and serum glucose (all P<0.05). AVC was a marker of higher prevalence
      (P<0.01) and severity of CAD (CAC score: 441+/-802 versus 265+/-566, P<0.05)
      independently of age. After follow-up of 3.8+/-0.9 years, AVC score increased
      (94+/-271 versus 54+/-173, P<0.01, +11+/-32 U/year), faster with higher baseline
      AVC score (P<0.01). Compared with participants remaining free of AVC, de novo
      acquisition of AVC was associated with higher LDL-cholesterol (141+/-31 versus
      121+/-27 mg/dL, P<0.05) and faster CAC progression (+78+/-87 versus +28+/-47
      U/year, P<0.05). In multivariate analysis, LDL-cholesterol independently
      determined AVC acquisition while higher baseline AVC scores determined faster
      progression of existing AVC. CONCLUSION: In the population, AVC is frequent with
      aging and atherosclerotic risk factors. AVC is a marker of subclinical CAD. AVC
      is progressive, appearing de novo with progressive atherosclerosis whereas
      established AVC progresses independently of atherosclerotic risk factors and
      faster with increasing initial AVC loads.

PMID- 17185621
TI  - Homocysteinylation of metallothionein impairs intracellular redox homeostasis:
      the enemy within!

PMID- 17185622
TI  - Nox 4 regulation of vascular smooth muscle cell differentiation marker gene
      expression.

PMID- 17185626
TI  - Endogenous secretory receptor for advanced glycation endproducts levels are
      correlated with serum pentosidine and CML in patients with type 1 diabetes.

PMID- 17185623
TI  - Neointimal cracks (plaque rupture?) and thrombosis in wrapped arteries without
      flow.

PMID- 17185627
TI  - Circulating platelet-derived microparticles are associated with atherothrombotic
      events: a marker for vulnerable blood.

PMID- 17185628
TI  - Glutathiolation regulates tumor necrosis factor-alpha-induced caspase-3 cleavage
      and apoptosis: key role for glutaredoxin in the death pathway.
AB  - Caspase-3 cleavage and activation are known to play central roles in apoptosis.
      However, the mechanisms that regulate caspase-3 cleavage remain elusive.
      Glutaredoxin (Grx) is a ubiquitous redox molecule that is unique in its ability
      to regulate S-glutathiolation (glutathiolation) of proteins. Here we show the
      essential role of Grx in caspase-3 cleavage via regulation of caspase-3
      glutathiolation. Grx activity was significantly upregulated by tumor necrosis
      factor-alpha in endothelial cells. Small interference RNA knock down of Grx
      significantly inhibited tumor necrosis factor-alpha-induced endothelial cell
      death because of attenuated caspase-3 cleavage concomitant with increased caspase
      3 glutathiolation. Enhanced caspase-3 cleavage by wild-type Grx overexpression
      was reversed by catalytically inactive Grx (C22S), demonstrating a requirement
      for thioltransferase activity. Cysteine-to-serine mutations (C163S, C184S, and
      C220S) of caspase-3 that were predicted to prevent glutathiolation showed
      increased cleavage compared with wild-type caspase-3. This inverse correlation
      between caspase-3 glutathiolation and cleavage was further confirmed by the
      observation that in vitro glutathiolation of caspase-3 inhibited its cleavage
      with recombinant caspase-8. Furthermore, Grx association with caspase-3 was
      decreased by tumor necrosis factor-alpha. These findings demonstrate a novel
      mechanism of caspase-3 regulation by Grx in tumor necrosis factor-alpha-induced
      apoptosis.

PMID- 17185630
TI  - Role of heat shock protein 70 in hepatic ischemia-reperfusion injury in mice.
AB  - It is well established that liver ischemia-reperfusion induces the expression of
      heat shock protein (HSP) 70. However, the biological function of HSP70 in this
      injury is unclear. In this study, we sought to determine the role of HSP70 in
      hepatic ischemia-reperfusion injury in mice. Male mice were subjected to 90 min
      of partial hepatic ischemia followed by up to 8 h of reperfusion. HSP70 was
      rapidly upregulated after reperfusion. To explore the function of HSP70, sodium
      arsenite (8 mg/kg iv) was injected before surgery. We found that this dose
      induced HSP70 expression within 6 h of treatment. Induction of HSP70 with
      arsenite resulted in a >50% reduction in liver injury as determined by serum
      transaminases and histology. In addition, arsenite similarly reduced liver
      neutrophil recruitment and liver nuclear factor-kappaB activation, and attenuated
      serum levels of tumor necrosis factor-alpha and macrophage inflammatory protein
      2, but increased levels of interleukin (IL)-6. In HSP70 knockout mice, arsenite
      did not protect against liver injury but did reduce liver neutrophil
      accumulation. Arsenite-induced reductions in neutrophil accumulation in HSP70
      knockout mice were found to be mediated by IL-6. To determine whether
      extracellular HSP70 contributed to the injury, recombinant HSP70 was injected
      before surgery. Intravenous injection of 10 microg of recombinant HSP70 had no
      effect on liver injury after ischemia-reperfusion. The data suggest that
      intracellular HSP70 is directly hepatoprotective during ischemia-reperfusion
      injury and that extracellular HSP70 is not a significant contributor to the
      injury response in this model. Targeted induction of HSP70 may represent a
      potential therapeutic option for postischemic liver injury.

PMID- 17185631
TI  - fMLP induces Hsp27 expression, attenuates NF-kappaB activation, and confers
      intestinal epithelial cell protection.
AB  - Sustained expression of cytoprotective intestinal epithelial heat shock proteins
      (Hsps), particularly Hsp27, depends on stimuli derived from bacterial flora. In
      this study, we examined the role of the bacterial chemotactic peptide fMLP in
      stimulating colonic epithelial Hsp expression at concentrations encountered in a
      physiological milieu. Treatment of the polarized human intestinal epithelial cell
      line Caco2bbe with physiological concentrations of fMLP (10-100 nM) induced
      expression of Hsp27, but not Hsp72, in a time- and concentration-dependent
      manner. Induction of Hsp27 by fMLP was specific since the fMLP analogs MRP and
      MLP were not effective. Hsp27 induction by fMLP was blocked by the fMLP-receptor
      antagonist BOC-FLFLF and was blocked when the dipeptide transporter PepT1, an
      entry pathway for fMLP, was silenced. fMLP activated both the p38 and ERK1/2 MAP
      kinase pathways in Caco2bbe cells, but not the SAPK/JNK pathway. The p38
      inhibitor SB203580, but not the MEK-1 inhibitor PD98059, blocked Hsp27 induction
      by fMLP. fMLP treatment inhibited actin depolymerization and decreased
      transepithelial resistance caused by the oxidant monochloramine, and this
      inhibition was reversed by silencing Hsp27 expression. fMLP pretreatment also
      inhibited activation of proinflammatory transcription factor NF-kappaB by TNF
      alpha in Caco2bbe cells, reducing induction of NF-kappaB target genes by TNF
      alpha both in human intestinal biopsies and Caco2bbe cells. In conclusion, fMLP
      may contribute to the maintenance of intestinal homeostasis by mediating
      physiological expression of Hsp27, enhancing cellular protection, and negatively
      regulating the inflammatory response.

PMID- 17185629
TI  - Lipopolysaccharide opposes the induction of CYP26A1 and CYP26B1 gene expression
      by retinoic acid in the rat liver in vivo.
AB  - Retinoic acid (RA), a principal metabolite of vitamin A (retinol), is an
      essential endogenous regulator of gene transcription and an important therapeutic
      agent. The catabolism of RA must be well regulated to maintain physiological
      concentrations of RA. The cytochrome P450 (CYP) gene family CYP26, which encodes
      RA-4-hydroxylase activity, is strongly implicated in the oxidation of RA.
      Inflammation alters the expression of numerous genes; however, whether
      inflammation affects CYP26 expression is not well understood. We investigated the
      regulation of CYP26A1 and CYP26B1 mRNA levels by RA and LPS in the rat liver, as
      the liver is centrally involved in retinoid metabolism and the acute-phase
      response to LPS. Both CYP26A1 and CYP26B1 mRNA were induced in <4 h by a single
      oral dose of all-trans-RA. RA-induced responses of both CYP26A1 and CYP26B1 were
      significantly attenuated in rats with LPS-induced inflammation whether LPS was
      given concurrently with RA or after the RA-induced increase in CYP26A1 and
      CYP26B1 mRNA levels. When RA and LPS were administered simultaneously (6-h
      study), LPS alone had little effect on either CYP26A1 or CP26B1 mRNA, but LPS
      reduced by 80% the RA-induced increase in CYP26A1 mRNA (P<0.02), with a similar
      trend for CYP26B1 mRNA. When LPS was administered 4 h after RA (16-h study), it
      abrogated the induction of CYP26A1 (P<0.02) and CYP26B1 (P<0.01). Overall, these
      results suggest that inflammation can potentially disrupt the balance of RA
      metabolism and maintenance of RA homeostasis, which may possibly affect the
      expression of other RA-regulated genes.

PMID- 17185632
TI  - Inducible cAMP early repressor suppresses gastrin-mediated activation of cyclin
      D1 and c-fos gene expression.
AB  - The gastric hormone gastrin and its precursors promote proliferation in several
      gastrointestinal cell types. Here we show that gastrin induces transcription of
      cell cycle gene cyclin D1 and protooncogene c-fos in the neuroendocrine
      pancreatic cell line AR42J and that this gastrin response is inhibited by
      endogenous inducible cAMP early repressor (ICER). The transcriptional repressor
      ICER is known to downregulate both its own expression and the expression of other
      genes containing cAMP-responsive elements (CREs). Using siRNA, we also show that
      CRE promoter elements are the targets of endogenous ICER in AR42J cells as well
      as in the neuroendocrine cell line RIN5F. Our results suggest that ICER plays an
      important role in molecular mechanisms governing gastrin-mediated growth by
      modulating gastrin's transcriptional activation of growth-related genes. Our
      finding that ICER modulates pituitary adenylate cyclase-activating polypeptide
      activated gene expression also indicates a regulatory effect of ICER in the
      responses of neuroendocrine cells to peptides other than gastrin.

PMID- 17185633
TI  - CaM kinase II activation and phospholamban phosphorylation by SNP in murine
      gastric antrum smooth muscles.
AB  - Elevations in the intracellular Ca(2+) concentration activate the
      serine/threonine protein kinase Ca(2+)/calmodulin-dependent protein kinase II
      (CaM kinase II). We tested the hypothesis that increased sarco(endo)plasmic
      reticulum Ca(2+)-ATPase activity by phospholamban (PLB) phosphorylation
      contributes to smooth muscle relaxation by elevating the sarcoplasmic reticulum
      (SR) Ca(2+) load and increasing the frequency of Ca(2+) release events from the
      SR. We have previously shown that caffeine or sodium nitroprusside (SNP) relaxes
      murine gastric fundus smooth muscles and increases PLB phosphorylation by CaM
      kinase II. These findings suggest that an increased SR Ca(2+) load increases the
      frequency of Ca(2+) transients from the SR and results in PLB phosphorylation by
      CaM kinase II, contributing to caffeine- or SNP-induced relaxation. The aim of
      the present study was to investigate the effects of SNP on CaM kinase II and PLB
      phosphorylation in gastric antrum smooth muscles. SNP or 8-bromo-cGMP decreased
      the basal tone and amplitudes of spontaneous phasic contractions and activated
      CaM kinase II. SNP-induced relaxation and CaM kinase II activation were blocked
      by [1,2,4]oxadizolo-[4,3alpha]quinoxaline-1-one (ODQ) and inhibited by
      cyclopiazonic acid (CPA) or KN-93. SNP also increased PLBSer(16) and PLBThr(17)
      phosphorylation. Both PLBSer(16) and Thr(17) phosphorylation were ODQ sensitive.
      However, only PLBThr(17) phosphorylation was inhibited by CPA or KN-93. These
      results suggest that CaM kinase II activation and PLB phosphorylation participate
      in the relaxant effect of SNP on murine gastric antrum smooth muscles through a
      nitric oxide/guanylyl cyclase/cGMP pathway.

PMID- 17185635
TI  - Deriving number-needed-to-treat and number-needed-to-harm from the SAINT I trial
      results.

PMID- 17185636
TI  - Effect of nicardipine prolonged-release implants on cerebral vasospasm and
      clinical outcome after severe aneurysmal subarachnoid hemorrhage: a prospective,
      randomized, double-blind phase IIa study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effect
      of nicardipine prolonged-release implants (NPRIs) on cerebral vasospasm and
      clinical outcome after severe subarachnoid hemorrhage. METHODS: Thirty-two
      patients with severe subarachnoid hemorrhage and undergoing aneurysm clipping
      were included into this single center, randomized, double-blind trial. Sixteen
      patients received NPRIs implanted into the basal cisterns in direct contact to
      the exposed proximal blood vessels; in 16 control patients, the basal cisterns
      were opened and washed out only without leaving implants. Angiography was
      performed preoperatively and at day 8+/-1. Computed tomography imaging was
      analyzed for the incidence of territorial infarcts unrelated to surgery. Patient
      outcome was assessed using the modified Rankin and National Institute of Health
      Stroke scales. RESULTS: The incidence of angiographic vasospasm in proximal
      vessel segments was significantly reduced after implantation of NPRIs (73%
      control versus 7% NPRIs). Significant differences occurred also for the majority
      of distal vessel segments. Computed tomography scans revealed a lower incidence
      of delayed ischemic lesions (47% control versus 14% NPRIs). The NPRI group
      demonstrated more favorable modified Rankin and National Institute of Health
      Stroke scales as well as a significantly lower incidence of deaths (38% control
      versus 6% NPRIs). CONCLUSIONS: Implantation of NPRIs reduces the incidence of
      cerebral vasospasm and delayed ischemic deficits and improves clinical outcome
      after severe subarachnoid hemorrhage.

PMID- 17185634
TI  - Altered expression of genes regulating skeletal muscle mass in the portacaval
      anastomosis rat.
AB  - We examined the temporal relationship between portacaval anastomosis (PCA),
      weight gain, changes in skeletal muscle mass and molecular markers of protein
      synthesis, protein breakdown, and satellite cell proliferation and
      differentiation. Male Sprague-Dawley rats with end to side PCA (n=24) were
      compared with sham-operated pair-fed rats (n=24). Whole body weight, lean body
      mass, and forelimb grip strength were determined at weekly intervals. The
      skeletal muscle expression of the ubiquitin proteasome system, myostatin, its
      receptor (the activin 2B receptor) and its signal, cyclin-dependent kinase
      inhibitor (CDKI) p21, insulin-like growth factor (IGF)-I and its receptor (IGF-I
      receptor-alpha), and markers of satellite cell proliferation and differentiation
      were quantified. PCA rats did not gain body weight and had lower lean body mass,
      forelimb grip strength, and gastrocnemius muscle weight. The skeletal muscle
      expression of the mRNA of ubiquitin proteasome components was higher in PCA rats
      in the first 2 wk followed by a lower expression in the subsequent 2 wk (P<0.01).
      The mRNA and protein of myostatin, activin 2B receptor, and CDKI p21 were higher,
      whereas IGF-I and its receptor as well as markers of satellite cell function
      (proliferating nuclear cell antigen, myoD, myf5, and myogenin) were lower at
      weeks 3 and 4 following PCA (P < 0.05). We conclude that PCA resulted in
      uninhibited proteolysis in the initial 2 wk. This was followed by an adaptive
      response in the later 2 wk consisting of an increased expression of myostatin
      that may have contributed to reduced muscle protein synthesis, impaired satellite
      cell function, and lower skeletal muscle mass.

PMID- 17185637
TI  - Shoulder pain after stroke: a prospective population-based study.
AB  - BACKGROUND AND PURPOSE: Shoulder pain is a well-known complication after stroke,
      but data on prevalence, predictors, and outcome in unselected stroke populations
      are limited. METHODS: During a 1-year period, 416 first-ever stroke patients were
      included in the population-based Lund Stroke Register. After 4 months, 327
      patients were followed up and 1 year later, the surviving 305 patients were
      followed up again. General status (National Institutes of Health Stroke Scale
      score) was registered at stroke onset. Shoulder pain intensity (visual analog
      scale, score 0 to 30=no-mild and 40 to 100=moderate-severe pain); arm motor
      function; restricted dressing and/or ambulating; and functional status (Barthel
      Index) were registered at both follow ups. RESULTS: Shoulder pain onset within 4
      months after stroke was reported by 71 patients (22%). Among the 61 patients able
      to score the visual analog scale, 79% had moderate-severe pain. One year later, 8
      of these 71 patients had died, 17 had no remaining pain, and 28 additional
      patients had developed shoulder pain since the first follow up. Lost or impaired
      arm motor function and high National Institutes of Health Stroke Scale score were
      predictors of shoulder pain. Shoulder pain restricted daily life often or
      constantly when dressing for 51%/31% and when ambulating for 29%/13% of the
      patients at 4 and 16 months, respectively. CONCLUSIONS: Almost one third of the
      327 patients developed shoulder pain after stroke onset, a majority with moderate
      severe pain. Shoulder pain restricts patients' daily life after stroke. The
      increased risk of shoulder pain for patients with impaired arm motor function
      and/or low general status needs close attention in poststroke care.

PMID- 17185639
TI  - Is the severity of sleep apnea associated with ischemic stroke in the elderly?

PMID- 17185641
TI  - Hemorrhagic complications after off-label thrombolysis for ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Only 2% to 4% of patients with acute ischemic stroke
      receive thrombolytic therapy resulting from the current strict inclusion criteria
      among other issues. Safety of intravenous and intraarterial thrombolysis in off
      label situations is controversially discussed. We sought to review the reports on
      such patients regarding intra- and extracranial hemorrhage. SUMMARY OF REVIEW: A
      MEDLINE search for off-label uses of thrombolysis revealed reports on 273
      patients treated with intraarterial or intravenous thrombolysis for ischemic
      stroke. Symptomatic intracranial hemorrhage occurred in 19 of 273 patients
      (6.95%) and extracranial hemorrhage in 17 of 273 (6.22%). CONCLUSIONS: These data
      suggest that the overall bleeding risk in off-label thrombolysis may not be as
      high as presumed. However, the small number of patients in each group and the
      likely underreporting of worse outcomes preclude drawing any conclusion as to
      specific treatment recommendations. Selected patients might benefit, however,
      from thrombolysis in situations not currently considered in the inclusion
      criteria. To obtain a meaningful database, a registry for off-label thrombolysis
      should be created.

PMID- 17185643
TI  - Molecular refinement of gibbon genome rearrangements.
AB  - The gibbon karyotype is known to be extensively rearranged when compared to the
      human and to the ancestral primate karyotype. By combining a bioinformatics
      (paired-end sequence analysis) approach and a molecular cytogenetics approach, we
      have refined the synteny block arrangement of the white-cheeked gibbon (Nomascus
      leucogenys, NLE) with respect to the human genome. We provide the first detailed
      clone framework map of the gibbon genome and refine the location of 86
      evolutionary breakpoints to <1 Mb resolution. An additional 12 breakpoints,
      mapping primarily to centromeric and telomeric regions, were mapped to
      approximately 5 Mb resolution. Our combined FISH and BES analysis indicates that
      we have effectively subcloned 49 of these breakpoints within NLE gibbon BAC
      clones, mapped to a median resolution of 79.7 kb. Interestingly, many of the
      intervals associated with translocations were gene-rich, including some genes
      associated with normal skeletal development. Comparisons of NLE breakpoints with
      those of other gibbon species reveal variability in the position, suggesting that
      chromosomal rearrangement has been a longstanding property of this particular ape
      lineage. Our data emphasize the synergistic effect of combining computational
      genomics and cytogenetics and provide a framework for ultimate sequence and
      assembly of the gibbon genome.

PMID- 17185644
TI  - Evidence for large inversion polymorphisms in the human genome from HapMap data.
AB  - Knowledge about structural variation in the human genome has grown tremendously
      in the past few years. However, inversions represent a class of structural
      variation that remains difficult to detect. We present a statistical method to
      identify large inversion polymorphisms using unusual Linkage Disequilibrium (LD)
      patterns from high-density SNP data. The method is designed to detect chromosomal
      segments that are inverted (in a majority of the chromosomes) in a population
      with respect to the reference human genome sequence. We demonstrate the power of
      this method to detect such inversion polymorphisms through simulations done using
      the HapMap data. Application of this method to the data from the first phase of
      the International HapMap project resulted in 176 candidate inversions ranging
      from 200 kb to several megabases in length. Our predicted inversions include an
      800-kb polymorphic inversion at 7p22, a 1.1-Mb inversion at 16p12, and a novel
      1.2-Mb inversion on chromosome 10 that is supported by the presence of two
      discordant fosmids. Analysis of the genomic sequence around inversion breakpoints
      showed that 11 predicted inversions are flanked by pairs of highly homologous
      repeats in the inverted orientation. In addition, for three candidate inversions,
      the inverted orientation is represented in the Celera genome assembly. Although
      the power of our method to detect inversions is restricted because of inherently
      noisy LD patterns in population data, inversions predicted by our method
      represent strong candidates for experimental validation and analysis.

PMID- 17185645
TI  - The origin and evolution of human ampliconic gene families and ampliconic
      structure.
AB  - Out of the nine male-specific gene families in the human Y chromosome amplicons,
      we investigate the origin and evolution of seven families for which gametologous
      and orthologous sequences are available. Proto-X/Y gene pairs in the original
      mammalian sex chromosomes played major roles in origins and gave rise to five
      gene families: XKRY, VCY, HSFY, RBMY, and TSPY. The divergence times between
      gametologous X- and Y-linked copies in these families are well correlated with
      the former X-chromosomal locations. The CDY and DAZ families originated
      exceptionally by retroposition and transposition of autosomal copies,
      respectively, but CDY possesses an X-linked copy of enigmatic origin. We also
      investigate the evolutionary relatedness among Y-linked copies of a gene family
      in light of their ampliconic locations (palindromes, inverted repeats, and the
      TSPY array). Although any pair of copies located at the same arm positions within
      a palindrome is identical or nearly so by frequent gene conversion, copies
      located at different arm positions are distinctively different. Since these and
      other distinct copies in various gene families were amplified almost
      simultaneously in the stem lineage of Catarrhini, we take these simultaneous
      amplifications as evidence for the elaborate formation of Y ampliconic structure.
      Curiously, some copies in a gene family located at different palindromes exhibit
      high sequence similarity, and in most cases, such similarity greatly extends to
      repeat units that harbor these copies. It appears that such palindromic repeat
      units have evolved by and large en bloc, but they have undergone frequent
      exchanges between palindromes.

PMID- 17185646
TI  - Occupational risk factors and asthma among health care professionals.
AB  - RATIONALE: Recent U.S. data suggest an increased risk of work-related asthma
      among health care workers, yet only a few specific determinants have been
      elucidated. OBJECTIVES: To evaluate associations of asthma prevalence with
      occupational exposures in a cross-sectional survey of health care professionals.
      METHODS: A detailed questionnaire was mailed to a random sample (n=5,600) of all
      Texas physicians, nurses, respiratory therapists, and occupational therapists
      with active licenses in 2003. Information on asthma symptoms and nonoccupational
      asthma risk factors obtained from the questionnaire was linked to occupational
      exposures derived through an industry-specific job-exposure matrix. MEASUREMENTS:
      There were two a priori defined outcomes: (1) physician-diagnosed asthma with
      onset after entry into health care ("reported asthma") and (2) "bronchial
      hyperresponsiveness-related symptoms," defined through an 8-item symptom-based
      predictor. MAIN RESULTS: Overall response rate was 66%. The final study
      population consisted of 862 physicians, 941 nurses, 968 occupational therapists,
      and 879 respiratory therapists (n=3,650). Reported asthma was associated with
      medical instrument cleaning (odds ratio [OR], 2.22; 95% confidence interval [CI],
      1.34-3.67), general cleaning (OR, 2.02; 95% CI, 1.20-3.40), use of powdered latex
      gloves between 1992 and 2000 (OR, 2.17; 95% CI, 1.27-3.73), and administration of
      aerosolized medications (OR, 1.72; 95% CI, 1.05-2.83). The risk associated with
      latex glove use was not apparent after 2000. Bronchial hyperresponsiveness
      related symptoms were associated with general cleaning (OR, 1.63; 95% CI, 1.21
      2.19), aerosolized medication administration (OR, 1.40; 95% CI, 1.06-1.84), use
      of adhesives on patients (OR, 1.65; 95% CI, 1.22-2.24), and exposure to a
      chemical spill (OR, 2.02; 95% CI, 1.28-3.21). CONCLUSIONS: The contribution of
      occupational exposures to asthma in health care professionals is not trivial,
      meriting both implementation of appropriate controls and further study.

PMID- 17185648
TI  - Endurance training damages small airway epithelium in mice.
AB  - RATIONALE: In athletes, airway inflammatory cells were found to be increased in
      induced sputum or bronchial biopsies. Most data were obtained after exposure to
      cold and dry air at rest or during exercise. Whether training affects epithelial
      and inflammatory cells in small airways is unknown. OBJECTIVES: To test whether
      endurance training under standard environmental conditions causes epithelial
      damage and inflammation in the small airways of mice. METHODS AND MEASUREMENTS:
      Formalin-fixed, paraffin-embedded lung sections were obtained in sedentary (n =
      14) and endurance-trained (n = 16) Swiss mice at baseline and after 15, 30, and
      45 days of training. The following variables were assessed (morphometry and
      immunohistochemistry) in small airways (basement membrane length < 1 mm): (1)
      integrity, proliferation, and apoptosis of bronchiolar epithelium; and (2)
      infiltration, activation, and apoptosis of inflammatory cells. MAIN RESULTS:
      Compared with sedentary mice, bronchiolar epithelium of trained mice showed
      progressive loss of ciliated cells, slightly increased thickness, unchanged
      goblet cell number and appearance, and increased apoptosis and proliferation
      (proliferating cell nuclear antigen) (p < 0.001 for all variables). Leukocytes
      (CD45(+) cells) infiltrated airway walls (p < 0.0001) and accumulated within the
      lumen (p < 0.001); however, apoptosis of CD45(+) cells did not differ between
      trained and sedentary mice. Nuclear factor-kappaB translocation and inhibitor
      alpha of NF-kappaB (IkappaBalpha) phosphorylation were not increased in trained
      compared with sedentary mice. CONCLUSIONS: Bronchiolar epithelium showed damage
      and repair associated with endurance training. Training increased inflammatory
      cells in small airways, but inflammatory activation was not increased. These
      changes may represent an adaptive response to increased ventilation during
      exercise.

PMID- 17185647
TI  - Inhaled corticosteroids and risk of lung cancer among patients with chronic
      obstructive pulmonary disease.
AB  - RATIONALE AND OBJECTIVES: Lung cancer is a frequent cause of death among patients
      with chronic obstructive pulmonary disease (COPD). We examined whether the use of
      inhaled corticosteroids among patients with COPD was associated with a decreased
      risk of lung cancer. METHODS: We performed a cohort study of United States
      veterans enrolled in primary care clinics between December 1996 and May 2001.
      Participants had received treatment for, had an International Classification of
      Disease, 9th edition, diagnosis of, or a self-reported diagnosis of COPD.
      Patients with a history of lung cancer were excluded. To be exposed, patients
      must have been at least 80% adherent to inhaled corticosteroids. We used Cox
      regression models to estimate the risk of cancer and adjust for potential
      confounding factors. FINDINGS: We identified 10,474 patients with a median follow
      up of 3.8 years. In comparison to nonusers of inhaled corticosteroids, adjusting
      for age, smoking status, smoking intensity, previous history of non-lung cancer
      malignancy, coexisting illnesses, and bronchodilator use, there was a dose
      dependent decreased risk of lung cancer associated with inhaled corticosteroids
      (ICS dose < 1,200 mug/d: adjusted HR, 1.3; 95% confidence interval, 0.67-1.90;
      ICS dose >or= 1,200 microg/d: adjusted HR, 0.39; 95% confidence interval, 0.16
      0.96). Changes in cohort definitions had minimal effects on the estimated risk.
      Analyses examining confounding by indication suggest biases in the opposite
      direction of the described effects. INTERPRETATION: Results suggest that inhaled
      corticosteroids may have a potential role in lung cancer prevention among
      patients with COPD. These initial findings require confirmation in separate and
      larger cohorts.

PMID- 17185649
TI  - CD14 facilitates invasive respiratory tract infection by Streptococcus
      pneumoniae.
AB  - RATIONALE: CD14 is a pattern recognition receptor that can interact with a
      variety of bacterial ligands. During gram-negative infection, CD14 plays an
      important role in the induction of a protective immune response by virtue of its
      capacity to recognize lipopolysaccharide in the bacterial cell wall. Knowledge of
      the contribution of CD14 to host defense against gram-positive infections is
      limited. OBJECTIVES: To study the role of CD14 in gram-positive bacterial
      pneumonia. METHODS: CD14 knockout (KO) and normal wild-type (WT) mice were
      intranasally infected with Streptococcus pneumoniae. MEASUREMENTS AND MAIN
      RESULTS: CD14 KO mice demonstrated a strongly reduced lethality, which was
      accompanied by a more than 10-fold lower bacterial load in lung homogenates but
      not in bronchoalveolar lavage fluid at 48 hours after infection. Strikingly, CD14
      KO mice failed to develop positive blood cultures, whereas WT mice had positive
      blood cultures from 24 hours onward and eventually invariably had evidence of
      systemic infection. Lung inflammation was attenuated in CD14 KO mice at 48 hours
      after infection, as evaluated by histopathology and cytokine and chemokine
      levels. Intrapulmonary delivery of recombinant soluble CD14 to CD14 KO mice
      rendered them equally susceptible to S. pneumoniae as WT mice, resulting in
      enhanced bacterial growth in lung homogenates and bacteremia, indicating that the
      presence of soluble CD14 in the bronchoalveolar compartment is sufficient to
      cause invasive pneumococcal disease. CONCLUSION: These data suggest that S.
      pneumoniae uses (soluble) CD14 present in the bronchoalveolar space to cause
      invasive respiratory tract infection.

PMID- 17185650
TI  - Increased prevalence of post-traumatic stress disorder symptoms in critical care
      nurses.
AB  - RATIONALE: Intensive care unit (ICU) nurses work in a demanding environment where
      they are repetitively exposed to traumatic situations and stressful events. The
      psychological effects on nurses as a result of working in the ICU are relatively
      unknown. OBJECTIVE: To determine whether there is an increased prevalence of
      psychological symptoms in ICU nurses when compared with general nurses. METHODS:
      We surveyed ICU and general nurses from three different hospitals (n=351) and
      then surveyed ICU nurses throughout the metropolitan area (n=140). MEASUREMENTS
      AND MAIN RESULTS: In both cohorts of nurses, we determined the prevalence of
      symptoms of post-traumatic stress disorder (PTSD), anxiety, and depression using
      validated survey instruments. Within our hospital system, 24% (54/230) of the ICU
      nurses tested positive for symptoms of PTSD related to their work environment,
      compared with 14% (17/121) of the general nurses (p=0.03). ICU nurses did not
      report a greater amount of stress in their life outside of the hospital than
      general nurses. There was no difference in symptoms of depression or anxiety
      between ICU and general nurses. In the second survey of ICU nurses from our
      metropolitan area, 29% (41/140) of the respondents reported symptoms of PTSD,
      similar to our first cohort of ICU nurses. CONCLUSIONS: ICU nurses have an
      increased prevalence of PTSD symptoms when compared with other general nurses.
      These results may increase awareness of these symptoms in nurses and lead to
      future interventions that improve their mental health and job satisfaction and
      help retain ICU nurses in their profession.

PMID- 17185652
TI  - Science to practice: why is the liver a radiosensitive organ?
AB  - Christiansen et al irradiated rat livers in vivo; isolated rat hepatocytes in
      vitro; and measured hepcidin, hemojuvelin, and ferroportin-1 gene expression.
      They also evaluated the influence of proinflammatory cytokines (interleukin [IL]-
      1beta, IL-6, and tumor necrosis factor [TNF]-alpha) on the expression of these
      proteins. In this issue of Radiology, Christiansen et al conclude that radiation
      induced cell-cell interactions by way of the cytokines can lead to death of
      irradiated hepatocytes.

PMID- 17185656
TI  - R. Gilbert Jost, MD, President, Radiological Society of North America, 2007.

PMID- 17185651
TI  - Leptin resistance protects mice from hyperoxia-induced acute lung injury.
AB  - RATIONALE: Human data suggest that the incidence of acute lung injury is reduced
      in patients with type II diabetes mellitus. However, the mechanisms by which
      diabetes confers protection from lung injury are unknown. OBJECTIVES: To
      determine whether leptin resistance, which is seen in humans with diabetes,
      protects mice from hyperoxic lung injury. METHODS: Wild-type (leptin responsive)
      and db/db (leptin resistant) mice were used in these studies. Mice were exposed
      to hyperoxia (100% O(2)) for 84 hours to induce lung injury and up to 168 hours
      for survival studies. Alveolar fluid clearance was measured in vivo. MEASUREMENTS
      AND MAIN RESULTS: Lung leptin levels were increased both in wild-type and leptin
      receptor-defective db/db mice after hyperoxia. Hyperoxia-induced lung injury was
      decreased in db/db compared with wild-type mice. Hyperoxia increased lung
      permeability in wild-type mice but not in db/db mice. Compared with wild-type
      control animals, db/db mice were resistant to hyperoxia-induced mortality (lethal
      dose for 50% of mice, 152 vs. 108 h). Intratracheal instillation of leptin at a
      dose that was observed in the bronchoalveolar lavage fluid during hyperoxia
      caused lung injury in wild-type but not in db/db mice. Intratracheal pretreatment
      with a leptin receptor inhibitor attenuated leptin-induced lung edema. The
      hyperoxia-induced release of proinflammatory cytokines was attenuated in db/db
      mice. Despite resistance to lung injury, db/db mice had diminished alveolar fluid
      clearance and reduced Na,K-ATPase function compared with wild-type mice.
      CONCLUSIONS: These results indicate that leptin can induce and that resistance to
      leptin attenuates hyperoxia-induced lung injury and hyperoxia-induced
      inflammatory cytokines in the lung.

PMID- 17185657
TI  - Evidence-based practice in radiology: an introduction to the series.

PMID- 17185658
TI  - Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II
      Investigators.

PMID- 17185659
TI  - Evidence-based radiology: steps 1 and 2--asking answerable questions and
      searching for evidence.
AB  - Evidence-based medicine originated at McMaster University, Hamilton, Ontario,
      Canada, where it was defined as "the integration of current best evidence with
      clinical expertise and patient values" by the Evidence-based Medicine Working
      Group led by Drs Gordon Guyatt and David Sackett. From this developed the
      McMaster University and National Health Service Centre for Evidence-Based
      Medicine, University of Oxford, paradigm of evidence-based practice, which
      consists of five steps that can be used by ordinary practitioners: formulate
      answerable questions with which to search for evidence, search the literature,
      appraise the retrieved evidence by using explicit methods, apply results to a
      patient or patient group, and evaluate one's evidence-based practice and clinical
      performance and practice. This communication is about the first two steps of this
      process. Step 1 provides a framework for more effective question formulation that
      improves subsequent literature searches. It works equally well for questions
      about diagnostic and interventional radiology. A clinical scenario for a
      diagnostic question is used to illustrate the formulation of an answerable
      question. This question is then used to illustrate step 2-how and where to search
      for evidence.

PMID- 17185660
TI  - The National Institute of Biomedical Imaging and Bioengineering and NIH grant
      process: an overview.
AB  - The National Institutes of Health (NIH) comprise the largest single source of
      funding in the world for the support of biomedical research. Much of the work of
      the NIH focuses on the elucidation of fundamental biophysical, biochemical, and
      biologic aspects of the molecular, cellular, and tissue processes underlying both
      healthy and diseased states of biologic systems and on the development of cures
      for the latter. In 2000, the National Institute of Biomedical Imaging and
      Bioengineering (NIBIB) was created with a somewhat different focus: Rather than
      concentration on a specific organ system or category of disease, the primary
      objective of the NIBIB is the advancement of technologies and tools that
      contribute to all aspects of biomedical research and health care delivery,
      especially in the imaging sciences and bioengineering. This article provides an
      overview of the ways in which NIH funds research, with an emphasis on NIBIB
      support of biomedical imaging. It is intended for radiologists, radiation
      oncologists, medical physicists, and other readers of this journal, especially
      those with limited experience in the complex process of obtaining NIH grant
      support.

PMID- 17185661
TI  - Importance of comparison of current and prior mammograms in breast cancer
      screening.
AB  - PURPOSE: To retrospectively determine the influence of comparing current
      mammograms with prior mammograms on breast cancer detection in screening and to
      investigate a protocol in which prior mammograms are viewed only when necessary.
      MATERIALS AND METHODS: Institutional review board approval was not required.
      Participants gave written informed consent. Twelve experienced screening
      radiologists read 160 soft-copy screening mammograms twice, once with and once
      without prior mammograms. Eighty mammograms were obtained in women in whom breast
      cancer was diagnosed later; the other 80 mammograms had been reported as normal
      or benign. All cancers were visible in retrospect. Readers located potential
      abnormalities, estimated likelihood of malignancy for each finding, and indicated
      whether prior mammograms were considered necessary. The effect of prior
      mammograms on detection was determined by computing the mean lesion localized
      fraction in a range of low fractions of nonlesion locations corresponding to
      operating points in screening. Scores for both reading sessions were combined to
      assess the effect of making prior mammograms available only when requested. Data
      were analyzed by comparing the number of localized lesions between the two
      reading conditions with a paired two-tailed Student t test and applying a linear
      mixed model to test differences in average mean lesion localized fraction between
      reading conditions. P values less than .05 indicated statistical significance.
      RESULTS: Without prior mammograms, significantly more annotations were made. When
      only positive cases were considered, no difference was observed. Reading
      performance was significantly better when prior screening mammograms were
      available. At fixed lesion localized fraction, nonlesion localized fraction was
      reduced by 44% (P<.001) on average when prior mammograms were read. Performance
      was also increased for combined reading mode (ie, when prior mammograms were
      available on request only). However, this increase was smaller than that when
      prior mammograms were always available. Prior mammograms were requested in 24%
      33% of all cases and were requested more often in positive cases. CONCLUSION:
      Comparison with prior mammograms significantly improves overall performance and
      can reduce referrals due to nonlesion locations. Limiting the availability of
      prior mammograms to cases selected by the reader reduces the beneficial effect of
      prior mammograms.

PMID- 17185662
TI  - Role of functional MR in determining language dominance in epilepsy and
      nonepilepsy populations: a Bayesian analysis.
AB  - PURPOSE: To determine the role of functional magnetic resonance (MR) imaging in
      assessing hemispheric language dominance in epilepsy and nonepilepsy populations.
      MATERIALS AND METHODS: A Bayesian analysis study was performed. The study was
      based on data from the published literature; thus, institutional review board
      approval was not required. The literature was reviewed to obtain pretest
      probabilities and likelihood ratios, which were analyzed to determine the
      posttest probability of language dominance by using functional MR imaging.
      Pretest probabilities of different hand dominances in epilepsy and nonepilepsy
      populations were obtained from the largest studies available in the literature.
      Likelihood ratios were derived from the sensitivity and specificity of functional
      MR imaging by using electrocortical stimulation (ECS) and the Wada test as
      reference standards. RESULTS: Likelihood ratios for functional MR in determining
      language dominance were 9.3 and 12.3 with ECS and the Wada test as reference
      standards, respectively. Use of functional MR increased the final posttest
      probabilities of hemispheric language dominance in epilepsy and nonepilepsy
      populations. In the nonepilepsy population, regardless of hand dominance, there
      was very high posttest probability (>or=96%) of a correlation between functional
      MR hemisphere activation and definite left-hemisphere language dominance. In the
      epilepsy population with right-hand dominance or ambidexterity, there was very
      high posttest probability (>or=95%) of a correlation between functional MR
      hemisphere activation and definite left-hemisphere language dominance. In the
      left-handed nonepileptic subjects, there was high posttest probability (81%-83%)
      of a correlation between functional MR hemisphere activation and definite right
      hemisphere language dominance. In the left-handed epilepsy population, there was
      high posttest probability (80%-97%) of a correlation between functional MR
      hemisphere activation and definite left-hemisphere language dominance. In the
      epilepsy population with ambidexterity, there was high posttest probability (80%
      87%) of correlations between functional MR hemisphere activation and both
      definite right-hemisphere and bilateral language dominance. CONCLUSION: Use of
      functional MR increases importantly the posttest probabilities of hemispheric
      language dominance in multiple subgroups of individuals with and without
      epilepsy.

PMID- 17185663
TI  - Multi-detector row CT attenuation measurements: assessment of intra- and
      interscanner variability with an anthropomorphic body CT phantom.
AB  - PURPOSE: To determine the dependence of absolute computed tomographic (CT)
      attenuation values on multi-detector row CT scanner type, convolution kernel, and
      tube current by using an anthropomorphic phantom. MATERIALS AND METHODS: A
      customized phantom was designed with tissue-equivalent materials to simulate
      contrast material-enhanced liver, spleen, pancreas, aorta, kidney, 0- and 50-HU
      cylindric renal cysts, muscle, and fat. The phantom was scanned with five multi
      detector row CT scanners (LightSpeed QXi, GE Healthcare, Milwaukee, Wis; MX8000,
      Philips Medical Systems, Best, the Netherlands; and Volume Zoom, Sensation 16 and
      Sensation 64, Siemens Medical Solutions, Forchheim, Germany) on five separate
      occasions with 120 kVp, low and high tube current settings, 3.00-3.75-mm section
      thickness, 50% overlap, and standard and high-spatial-resolution kernels.
      Standardized regions of interest (ROIs) were used to obtain 3510 attenuation
      measurements. Attenuation dependence on scanner, kernel, and tube current was
      evaluated by using F tests derived with mixed-model regression. Within the mixed
      model framework, the Tukey honestly significant difference procedure and a
      Bonferroni multiple comparison correction were used to assess differences among
      imaging regimens and tube current settings, respectively, in terms of tissue
      attenuation and ROI standard deviation. RESULTS: Tube current had no significant
      effect (P>.4) on observed tissue attenuation. Significant (P<.0001) differences
      were observed between imaging regimens with respect to mean attenuation for each
      tissue type. Convolution kernel modification had an inconsistent effect on tissue
      attenuation, depending on the scanner. All multi-detector row CT scanners
      displayed intrascanner variability in tissue attenuation (minimum range: 8.4 HU
      for fat tissue with the Sensation 16; maximum range: 63.4 HU for liver tissue
      with the Sensation 64). The scanners behaved differently at the lower range of
      the CT number scale, where 0-HU cyst attenuation ranged from -15.7 to 23.9 HU and
      one vendor's equipment showed significantly lower mean attenuation values.
      CONCLUSION: CT attenuation values vary significantly between different
      manufacturers' multi-detector row CT scanners, among different generations of
      multi-detector row CT scanning equipment, and with individual combinations of
      scanner and convolution kernel. SUPPLEMENTAL MATERIAL:
      http://radiology.rsnajnls.org/cgi/content/full/242/1/109/DC1

PMID- 17185664
TI  - Early ischemia in growing piglet skeleton: MR diffusion and perfusion imaging.
AB  - PURPOSE: To determine whether diffusion changes with ischemia of increasing
      duration, whether diffusion magnetic resonance (MR) imaging provides different
      information than does gadolinium-enhanced imaging, and which structural and/or
      biochemical changes are potentially responsible for any changes in diffusion.
      MATERIALS AND METHODS: Ischemia was surgically induced in one hip of each piglet
      (n=8) after approval from the Subcommittee on Research Animal Care; the other hip
      served as a control. Piglets were imaged at approximately 48 hours and 1, 2, 4,
      and 8 weeks after surgery at 1.5 T by using line-scan diffusion and dynamic
      gadolinium-enhanced MR imaging. Apparent diffusion coefficients (ADCs) and
      enhancement ratios (ERs) were calculated. Significant differences in ADC and ER
      values over time were evaluated by using the Student t test (P<.05). At 8 weeks,
      piglets were sacrificed for histologic evaluation. RESULTS: MR images of ischemic
      hips showed essentially no flow 48 hours after surgery. Spontaneous partial
      reperfusion was observed 1-4 weeks after surgery (ischemic ER/control ER=66%+/-35
      [standard deviation]), and the ER of the ischemic hips was well above that of the
      control hips at 8 weeks. The ADC of ischemic hips was elevated above that of
      control hips before reperfusion 1 week after surgery by 47%+/-12 and remained
      elevated despite flow restoration. Gross structural abnormalities on MR images
      appeared to coincide with reperfusion. Histologic findings revealed abnormal
      epiphyseal cartilage thickening, cartilaginous islands within ossified tissue,
      and less fatty marrow in ischemic hips than in control hips; all of these factors
      could explain elevated ADC. CONCLUSION: Diffusion is sensitive to early ischemia
      and follows a different time course than that of changes observed with gadolinium
      enhancement. ADC remained elevated in this model of severe, prolonged ischemia
      despite the spontaneous partial restoration of blood flow seen on gadolinium
      enhanced images.

PMID- 17185665
TI  - Predicting biliary complications in right lobe liver transplant recipients
      according to distance between donor's bile duct and corresponding hepatic artery.
AB  - PURPOSE: To retrospectively determine whether biliary complications in recipients
      of living-donor right lobe liver grafts can be predicted at pretransplantation
      donor computed tomography (CT). MATERIALS AND METHODS: The human research
      committee approved this study. The requirement for informed consent was waived.
      Multi-detector row CT cholangiography and CT angiography were performed in 44
      consecutive right lobe liver donors (25 men, 19 women; mean age, 37 years). When
      CT cholangiography in the donor demonstrated the right biliary anatomy
      (conventional or variant), the shortest distance between the right main (or
      second-order) hepatic artery and the corresponding right main (or second-order)
      bile duct was measured and compared with posttransplantation biliary
      complications in the transplant recipient by using generalized estimating
      equations. RESULTS: In 22 transplant recipients with one right main duct-to
      common duct anastomosis (ie, conventional donor anatomy), the distance between
      the donor's right main bile duct and hepatic artery generally was small (mean
      distance, 3.8 mm; range, 1-14 mm) and unrelated (P=.46) to biliary complications
      (n=6). In 22 recipients who required two second-order right duct anastomoses (ie,
      with variant donor anatomy), the distance between the donor's second-order duct
      and corresponding hepatic artery was more variable (mean distance, 6.6 mm; range,
      1-32.5 mm), and biliary complications were significantly more common when this
      distance was 10 mm or greater (in eight of 13 ducts with conventional anatomy and
      four of 31 ducts with variant anatomy, P<.05). CONCLUSION: Right lobe liver graft
      recipients who have variant right biliary anatomy and a second-order bile duct 10
      mm or farther from the corresponding hepatic artery are at high risk for biliary
      complications, possibly because of a predisposition to ischemic injury.

PMID- 17185666
TI  - Effect of directed training on reader performance for CT colonography:
      multicenter study.
AB  - PURPOSE: To define the interpretative performance of radiologists experienced in
      computed tomographic (CT) colonography and to compare it with that of novice
      observers who had undergone directed training, with colonoscopy as the reference
      standard. MATERIALS AND METHODS: Physicians at each participating center received
      ethical committee approval and followed the committees' requests regarding
      informed consent. Nine experienced radiologists, nine trained radiologists, and
      10 trained technologists from nine centers read 40 CT colonographic studies
      selected from a data set of 51 studies and modeled to simulate a population with
      positive fecal occult blood test results: Studies were obtained in eight patients
      with cancer, 12 patients with large polyp, four patients with medium polyp, and
      27 patients without colonic lesions. Findings were verified with colonoscopy. An
      experienced radiologist used 50 endoscopically validated studies to train novice
      observers before they were allowed to participate. Observers used one software
      platform to read studies over 2 days. Responses were collated and compared with
      the known diagnostic category for each subject. The number of correctly
      classified subjects was determined for each observer, and differences between
      groups were examined with bootstrap analysis. RESULTS: Overall, 28 observers read
      1084 studies and detected 121 cancers, 134 large polyps, and 33 medium polyps;
      448 healthy subjects were categorized correctly. Experienced radiologists
      detected 116 lesions; trained radiologists and technologists detected 85 and 87
      lesions, respectively. Overall accuracy of experienced observers (74.2%) was
      significantly better than that of trained radiologists (66.6%) and technologists
      (63.2%). There was no significant difference (P=.33) between overall accuracy of
      trained radiologists and that of technologists; however, some trainees reached
      the mean performance achieved by experienced observers. CONCLUSION: Experienced
      observers interpreted CT colonographic images significantly better than did
      novices trained with 50 studies. On average, no difference between trained
      radiologists and trained technologists was found; however, individual performance
      was variable and some trainees outperformed some experienced observers.

PMID- 17185667
TI  - Abdominal pain: coronal reformations from isotropic voxels with 16-section CT-
      reader lesion detection and interpretation time.
AB  - PURPOSE: To retrospectively assess if reader detection of intraabdominal
      pathologic findings on coronal reformations from isotropic voxels at 16-section
      computed tomography (CT) was similar to reader detection on transverse scans.
      MATERIALS AND METHODS: The institutional review board approved this HIPAA
      compliant study, and a waiver of informed consent was obtained. Twenty-nine
      consecutive patients (12 men, 17 women; mean age, 48 years; age range, 21-93
      years) with abdominal pain underwent 16-section CT with coronal reformations.
      Eight independent readers reviewed randomized scans (transverse and coronal) and
      identified pathologic findings in multiple organ systems. Timing for each
      interpretation was recorded. One month later, readers reviewed the scan
      reformatted in the other imaging plane. Agreement between transverse and coronal
      scans was measured by using Cohen kappa coefficients. RESULTS: Agreement was
      moderate to near perfect between transverse and coronal interpretations for
      intraabdominal anatomic and pathologic findings (kappa=0.59-1.00). For transverse
      interpretations, more thoracic pathologic findings were noted than for coronal
      interpretations; for coronal interpretations, more lymph nodes were noted than
      for transverse interpretations. Mean transverse interpretation time was 4.9
      minutes+/-1.1 (standard deviation) (range, 2.9-6.5 minutes); mean coronal
      interpretation time was 5.1 minutes+/-0.8 (range, 3.3-6.7 minutes). For each
      reader, there was no statistically significant difference in interpretation time
      between transverse and coronal scans (P=.06). CONCLUSION: With regard to the
      presence of intraabdominal pathologic findings, coronal reformations from
      isotropic voxels are similar to transverse scans in terms of interpretation time
      and reader agreement.

PMID- 17185668
TI  - Cell therapy in murine atherosclerosis: in vivo imaging with high-resolution
      helical SPECT.
AB  - PURPOSE: To determine the feasibility of in vivo localization and quantification
      of indium 111 (111In)-oxine-labeled bone marrow (BM) with high-resolution whole
      body helical single photon emission computed tomography (SPECT) in an established
      murine model of atherosclerosis and vascular repair. MATERIALS AND METHODS: The
      institutional animal care and use committee approved this study. BM from young B6
      Rosa 26 Lac Z+/+ mice was radiolabeled with 111In-oxine. On days 1, 4, and 7
      after administration of radiolabeled cells, five C57/BL6 apolipoprotein E
      deficient mice and five wild-type (WT) control mice were imaged with whole-body
      high-resolution helical SPECT. Quantification with SPECT was compared with ex
      vivo analysis by means of gamma counting. Autoradiography and beta-galactosidase
      staining were used to verify donor cell biodistribution. Linear regression was
      used to assess the correlation between continuous variables. Two-tailed Student t
      test was used to compare values between groups, and paired two-tailed t test was
      used to assess changes within subjects at different time points. RESULTS: SPECT
      image contrast was high, with clear visualization of BM, liver, and spleen 7 days
      after administration of radiolabeled cells. SPECT revealed that 42% and 58% more
      activity was localized to the aorta and BM (P<.05 for both), respectively, in
      apolipoprotein E-deficient mice versus WT mice. Furthermore, 28% and 27% less
      activity was localized to the liver and spleen (P<.05 for both), respectively, in
      apolipoprotein E-deficient mice versus WT mice. SPECT and organ gamma counts
      showed good quantitative correlation (r=0.9). beta-Galactosidase staining and
      microautoradiography of recipient aortas showed donor cell localization to the
      intima of visible atherosclerotic plaque but not to unaffected regions of the
      vessel wall. CONCLUSION: High-resolution in vivo helical pinhole SPECT can be
      used to monitor and quantify early biodistribution of 111In-oxine-labeled BM in a
      murine model of progenitor cell therapy for atherosclerosis.

PMID- 17185669
TI  - Chronic tibiofibular syndesmosis injury of ankle: evaluation with contrast
      enhanced fat-suppressed 3D fast spoiled gradient-recalled acquisition in the
      steady state MR imaging.
AB  - PURPOSE: To retrospectively determine the accuracy of coronal contrast material
      enhanced fat-suppressed three-dimensional (3D) fast spoiled gradient-recalled
      acquisition in the steady state (SPGR) magnetic resonance (MR) imaging, as
      compared with that of routine transverse MR imaging, in the assessment of distal
      tibiofibular syndesmosis injury, with arthroscopy as the reference standard.
      MATERIALS AND METHODS: The review board of the College of Medicine in Yonsei
      University approved this study; informed consent was waived. The study group
      comprised 45 patients (26 men, 19 women; mean age, 32.1 years; range, 18-58
      years) with a chronic ankle injury who had undergone MR imaging and arthroscopic
      surgery. Three independent readers retrospectively reviewed the two sets of MR
      images (one set of gadolinium-enhanced 3D fast SPGR images and one set of routine
      T1-, T2-, and intermediate-weighted images). Scores from 1 to 5 in increasing
      order of the probability of injury were assigned to both sets. Arthroscopy was
      the reference standard. Syndesmotic recess height was measured on contrast
      enhanced images. The two sets of images were compared for diagnostic performance
      with receiver operating characteristic (ROC) analysis. Dissection and histologic
      examination of six cadaveric ankles was performed to assess the syndesmotic area
      and ascertain the enhancing structure at MR imaging. RESULTS: At arthroscopy,
      syndesmotic injury was found in 24 ankles but not in 21 ankles. Areas under the
      ROC curve were significantly higher for the contrast-enhanced images (P<.05). The
      contrast-enhanced set showed higher accuracy, sensitivity, and specificity
      compared with the routine set for the assessment of syndesmosis injury. Mean
      syndesmotic recess height was significantly greater (P<.05) in patients with
      syndesmotic injury. Dissection and histologic examination revealed a highly
      vascular synovial fold in the syndesmotic area that is expected to enhance at MR
      imaging. CONCLUSION: In the assessment of chronic syndesmosis injury, coronal
      gadolinium-enhanced fat-suppressed 3D fast SPGR MR images were more sensitive,
      specific, and accurate than routine MR images.

PMID- 17185670
TI  - Normal-appearing white matter in patients with phenylketonuria: water content,
      myelin water fraction, and metabolite concentrations.
AB  - PURPOSE: To prospectively assess relative water content (RWC), myelin water
      fraction (MWF), and hydrogen 1 magnetic resonance (MR) spectroscopy findings in
      the white matter (WM) of patients with phenylketonuria (PKU). MATERIALS AND
      METHODS: This study was approved by the institution's investigational review
      board, and informed consent was obtained. T2 water relaxation data were acquired
      by using a 48-echo measurement in a transverse plane through the genu and
      splenium of the corpus callosum in 16 patients (six men, 10 women; age range, 18
      40 years) with PKU and 16 age- and sex-matched control subjects. MR spectroscopy
      was performed in a voxel (94x70x15 mm) above the ventricles. WM in control
      subjects (defined as normal WM) was compared with normal-appearing WM (NAWM) and
      diffuse WM lesions in patients with PKU by using a Student t test. RESULTS:
      Patients with PKU had two forms of NAWM: (a) areas that looked normal on
      intermediate-weighted (IW) and T2-weighted MR images and long T2 maps and (b)
      areas that looked normal on IW and T2-weighted MR images but were hyperintense on
      long T2 maps. Both forms of NAWM showed increased RWC (up to 2.5%, P<.001) and
      reduced MWF (up to 56%, P<.001) relative to normal WM; these changes paralleled
      those seen in diffuse WM lesions. Approximately 9% of the water in diffuse WM
      lesions was in a reservoir with a long T2 time of 200-800 msec. Myoinositol
      concentrations were reduced by 14% (P=.003) in patients with PKU. CONCLUSION: In
      patients with PKU, NAWM and diffuse WM lesions have altered RWC and MWF relative
      to normal WM, and diffuse WM lesions show a redistribution of water into an
      extracellular reservoir with a long T2 time.

PMID- 17185671
TI  - Leukocyte DNA damage after multi-detector row CT: a quantitative biomarker of low
      level radiation exposure.
AB  - PURPOSE: To prospectively determine if gammaH2AX (phosphorylated form of H2AX
      histone variant)-based visualization and quantification of DNA damage induced in
      peripheral blood mononuclear cells (PBMCs) can be used to estimate the radiation
      dose received by adult patients who undergo multidetector computed tomography
      (CT). MATERIALS AND METHODS: After institutional review board approval and
      written informed patient consent were obtained, eight women and five men (mean
      age, 63.8 years) who would be undergoing chest-abdominal-pelvic CT or chest CT
      only were recruited. Venous blood samples obtained before scanning were exposed
      to different radiation doses in vitro and incubated for 5-30 minutes to obtain
      reference values of gammaH2AX focus yield. Additional blood samples were taken 5
      30 minutes after CT. Leukocytes were isolated, fixed, and stained for gammaH2AX
      expression. The gammaH2AX focus yields were determined with fluorescence
      microscopy, and the radiation doses delivered during CT were estimated by
      comparing post-CT focus yields with in vitro pre-CT focus yields. These CT
      radiation doses were compared with doses calculated by using phantom dosimetry
      and Monte Carlo data sets. Data were analyzed by using linear regression, the
      dispersion index test, and the contaminated Poisson method. RESULTS: Compared
      with the gammaH2AX focus yields in blood samples taken before CT (0.06 focus per
      cell+/-0.01 [mean+/-standard error of mean]), the yields in blood samples taken 5
      minutes after chest-abdominal-pelvic CT (0.52 focus per cell+/-0.02) were 8-10
      fold higher and corresponded to a mean radiation dose of 16.4 mGy (95% confidence
      interval: 15.1, 17.7). The mean yield of 0.24 focus per cell+/-0.04 in one
      patient after chest CT corresponded to a mean radiation dose of 6.3 mGy+/-1.4. In
      comparison, phantom dosimetry-calculated total blood doses were 13.85 mGy with
      whole-body CT and 5.16 mGy with chest CT. CONCLUSION: gammaH2AX focus yield in
      blood cells may be a useful quantitative biomarker of human low-level radiation
      exposure.

PMID- 17185672
TI  - Peroneal tendon subluxation and dislocation: detection on volume-rendered images-
      initial experience.
AB  - Institutional review board approval was received and informed consent was not
      required for this Health Insurance Portability and Accountability Act-compliant
      study. The purpose of this study was to retrospectively assess the time
      efficiency of three-dimensional volume-rendered images obtained from multi
      detector row computed tomographic data for the diagnosis of peroneal tendon
      subluxation or dislocation by using the consensus interpretation of multiplanar
      reformatted (MPR) images as the reference standard. The reference standard was
      provided by two musculoskeletal radiologists, and two less experienced readers
      evaluated 37 images in 32 patients (24 men, eight women; mean age, 41 years; age
      range, 18-75 years) with acute calcaneal fractures. An analysis of variance was
      used to compare interpretation time, and the Wilcoxon signed rank test was used
      to analyze diagnostic difficulty. The average time required for diagnosis was
      significantly shorter with volume-rendered images than with MPR images (reader 1:
      42 vs 78 seconds, P<.001; reader 2: 50 vs 69 seconds, P<.01).

PMID- 17185675
TI  - Case 104: calcinosis in juvenile dermatomyositis.

PMID- 17185676
TI  - Case 105: left gastric artery aneurysm.

PMID- 17185677
TI  - The corkscrew sign: midgut volvulus.

PMID- 17185678
TI  - Please wait until I finish.

PMID- 17185679
TI  - Regarding "case 90: disseminated tuberculosis".

PMID- 17185680
TI  - Diagnosis please comment.

PMID- 17185681
TI  - Development of a research agenda for uterine artery embolization: proceedings
      from a multidisciplinary research consensus panel.

PMID- 17185682
TI  - SIR 2006 Annual Meeting Film Panel Case: Budd-Chiari syndrome in a patient with
      Cogan syndrome.

PMID- 17185683
TI  - SIR 2006 Annual Meeting Film Panel Case: granulomatous aortitis with type A
      aortic dissection and abdominal malperfusion: combined treatment approach with
      aortic fenestration and surgery.

PMID- 17185684
TI  - SIR 2006 Annual Meeting Film Panel Case: radiation-induced cerebral aneurysms.

PMID- 17185685
TI  - Embolization in the external carotid artery.
AB  - The technical skill set of peripheral interventional radiologists is well-suited
      to the performance of most transcatheter embolization procedures in the external
      carotid artery (ECA). These procedures center in large part on hypervascular
      tumors, epistaxis, and trauma. ECA embolization in the trauma patient is well
      defined, albeit in small patient series. The transcatheter treatment of epistaxis
      is still mostly reserved for cases that are intractable to conservative therapy.
      Preoperative embolotherapy for vascular tumors remains popular, although it is
      somewhat controversial in terms of its risk-benefit ratio. The purpose of this
      review is to highlight pertinent anatomy, selected technical procedural aspects,
      and the available literature to better characterize the role of ECA embolization
      in the hands of the practicing peripheral interventionist.

PMID- 17185686
TI  - Diagnostic accuracy of multislice CT angiography in peripheral arterial disease.
AB  - A systematic search of the PubMed and Medline databases of English literature was
      performed to determine the diagnostic accuracy of multislice computed tomographic
      (CT; MSCT) angiography in peripheral arterial disease (PAD) compared with digital
      subtraction angiography (DSA). Studies comparing MSCT angiography with DSA in
      peripheral vascular disease were included, and the diagnostic value of MSCT
      angiography in terms of sensitivity, specificity, and diagnostic accuracy was
      compared and analyzed. Ten studies (19 comparisons) met the criteria and were
      included for analysis. The pooled sensitivity, specificity, and accuracy rates
      were 92%, 91%, and 91%, respectively, at all arterial levels; 92%, 94%, and 93%,
      respectively, at aortoiliac arteries; 96%, 85%, and 92%, respectively, at
      femoropopliteal arteries; and 91%, 85%, and 87%, respectively, at infrapopliteal
      arteries. A significant difference was found in the sensitivity of MSCT
      angiography in PAD between four-slice CT and 16-slice CT, between aortoiliac and
      femoropopliteal arterial segments, and between femoropopliteal and infrapopliteal
      arterial segments (P<.05). This review demonstrates that MSCT angiography has a
      high diagnostic value and could be a reliable alternative to DSA in the diagnosis
      of PAD.

PMID- 17185687
TI  - Repeat uterine artery embolization: indications and technical findings.
AB  - PURPOSE: To determine the indications and technical aspects of procedures in
      patients undergoing repeat uterine artery embolization (UAE). MATERIALS AND
      METHODS: At a single center, 24 patients underwent repeat embolization for
      recurrent or persistent symptoms. The magnetic resonance (MR) imaging findings
      before repeat embolization were compared with those of earlier studies. The
      extent of tumor infarction after the first procedure was determined, and the
      status of existing or new tumors before the second procedure was assessed. The
      angiographic studies from the initial and repeat embolization studies were
      reviewed and summarized. These findings were assessed with the use of summary
      statistics. RESULTS: Twenty-four patients underwent repeat embolization 6-66
      months after the initial embolization. The most common symptom at representation
      was pressure and/or bulk symptoms (n=15), followed by recurrent heavy bleeding
      (n=12) and pelvic pain or cramping (n=7). MR imaging studies before repeat
      embolization revealed incomplete infarction of tumors present before the first
      embolization in 22 of 24 patients. New tumors were identified in 12 patients, two
      of whom had new tumors only. During repeat embolization, nine patients (37%)
      required ovarian artery embolization to occlude ovarian supply to the uterus.
      Among 21 women with clinical follow-up after the second embolization, 19 (90%)
      had symptom control. CONCLUSIONS: Repeat embolization prompted by recurrent
      uterine leiomyomas usually occurs in the setting of regrowth of incompletely
      infarcted tumors. Although ovarian embolization was often needed, on the basis of
      this limited experience, symptoms appear to respond well to repeat embolization.

PMID- 17185689
TI  - Clinical experience with a customized fenestrated endograft for juxtarenal
      abdominal aortic aneurysm repair.
AB  - Despite the numerous stent-graft devices available, unsuitable anatomy is still
      the greatest exclusion criterion for endovascular abdominal aortic aneurysm (AAA)
      repair (EVAR). The present report describes an on-site preprocedural
      customization of a conventional Zenith stent-graft device just before the
      endovascular procedure that includes the creation of fenestrations and scallops
      as necessary for the patient's anatomy. Three patients with difficult anatomy in
      whom conventional AAA repair posed a high degree of risk were treated with
      customization of the stent-graft device to fit disparate renal arteries. A single
      fenestration for the left renal artery was made in two cases, and a single
      scallop was made in the other case to accommodate the superior mesenteric artery.
      Gold beads were used to mark the location of the fenestration and scallop. The
      three cases were successfully performed without perceptible endoleaks in the
      follow-up period, which ranged from 4 to 14 months. No procedure-related
      complications were detected; however, pneumonia developed in one patient 3 weeks
      after EVAR. The initial results with this technique are encouraging, and the role
      of EVAR can be significantly increased with the use of this customization
      technique when the interventionalist does not have access to the commercially
      available devices or when the waiting time is too prolonged to accommodate the
      patient's clinical situation.

PMID- 17185688
TI  - Effectiveness of an aggressive antibiotic regimen for chemoembolization in
      patients with previous biliary intervention.
AB  - PURPOSE: Liver abscess occurs in most patients with biliary stents or bypass
      undergoing chemoembolization despite the use of standard prophylactic
      antibiotics. The present study was conducted to investigate the efficacy of an
      aggressive prophylactic regimen to prevent abscess in such patients. MATERIALS
      AND METHODS: Between November 2002 and July 2005, 16 chemoembolization procedures
      were performed in seven patients who had undergone biliary intervention.
      Prophylaxis was initiated with levofloxacin 500 mg daily and metronidazole 500 mg
      twice daily 2 days before chemoembolization and continued for 2 weeks after
      discharge. A bowel preparation regimen was given with neomycin 1 g plus
      erythromycin base 1 g orally at 1 p.m., 2 p.m., and 11 p. m. the day before
      chemoembolization. With the Fisher exact test, the incidence of infectious
      complications was compared with previously reported data for patients with and
      without earlier biliary intervention who had received standard prophylaxis.
      RESULTS: Liver abscess occurred in two of seven patients after two of 16
      procedures. Previously reported incidences were six of seven patients (P=.103)
      and six of 14 procedures (P=.101) among patients with previous biliary
      intervention receiving standard prophylaxis and one of 150 patients (P=.005) and
      one of 383 procedures (P=.004) among patients with no previous biliary
      intervention. CONCLUSIONS: There was a trend toward a lower rate of abscess
      formation among patients at high risk who received more aggressive antibiotic
      prophylaxis, but the difference did not reach statistical significance. The rate
      of infection remained significantly higher than among patients without previous
      biliary intervention.

PMID- 17185690
TI  - Percutaneous thrombin injection of a pulmonary artery pseudoaneurysm refractory
      to coil embolization.
AB  - A 57-year-old white man with a hypermetabolic right upper-lobe mass underwent
      treatment with wedge resection. During the immediate postoperative period, a
      right middle-lobe pulmonary artery pseudoaneurysm developed. After unsuccessful
      transcatheter coil embolization, fluoroscopically and sonographically guided
      percutaneous thrombin injection was performed, with complete thrombosis of the
      pseudoaneurysm.

PMID- 17185691
TI  - Treatment of intrauterine and large pedunculated subserosal leiomyomata with
      sequential uterine artery embolization and myomectomy.
AB  - Successful clinical outcomes were obtained after a combined therapy of uterine
      artery embolization (UAE) and subsequent myomectomy for gigantic subserosal
      leiomyoma exceeding 1,000 cm3 in volume on a short stalk and multiple
      intrauterine leiomyomata in young patients who desired fertility and uterine
      preservation. UAE effectively treated symptomatic multiple intramural and
      submucosal leiomyomata for menorrhagia symptoms, which also facilitated
      uncomplicated subsequent myomectomy with devascularized gigantic leiomyoma for
      the treatment of bulk symptoms.

PMID- 17185692
TI  - Successful portal-systemic shunt occlusion with balloon-occluded retrograde
      transvenous obliteration for portosystemic encephalopathy without liver
      cirrhosis.
AB  - A 68-year-old woman was admitted to the authors' hospital for hepatic
      encephalopathy. Her laboratory data and computed tomography findings were not
      suggestive of liver cirrhosis. Superior mesenteric angiography revealed an
      extrahepatic portal-systemic shunt with a main cause of hepatic encephalopathy.
      Despite treatment with branched-chain amino acid, lactulose, and kanamycin,
      hyperammonemia was prolonged, and the portal-systemic shunt was therefore treated
      with balloon-occluded retrograde transvenous obliteration. After the procedure,
      hyperammonemia was improved, and there were no signs of recurrent portal-systemic
      encephalopathy.

PMID- 17185693
TI  - A technique for controlled partial closure of a transjugular intrahepatic
      portosystemic shunt tract in a patient with hepatic encephalopathy.
AB  - A novel endovascular technique to reduce flow through a transjugular intrahepatic
      portosystemic shunt (TIPS) is described in a patient with severe hepatic
      encephalopathy. This technique allows controlled and potentially adjustable
      partial closure of the TIPS without thromboembolic risk. The patient experienced
      a dramatic clinical improvement after the procedure.

PMID- 17185694
TI  - Superior sensitivity of angiographic detection of arteriovenous fistula after
      biopsy in a renal allograft with CO2 compared with iodinated contrast medium.
AB  - Arteriovenous (AV) fistulas are potential complications of renal transplant
      biopsy procedures. In the setting of renal transplant failure, angiography with
      CO2 as a contrast agent is a useful adjunct to angiography with conventional
      contrast medium in the diagnosis and treatment of such fistulas with minimal
      nephrotoxicity. The present report describes a case of a renal transplant AV
      fistula seen after biopsy that could be detected angiographically only with CO2
      contrast medium.

PMID- 17185695
TI  - Use of hydrodissection to prevent nerve and muscular damage during radiofrequency
      ablation of kidney tumors.
AB  - Muscular complications are uncommon but have been reported after radiofrequency
      (RF) ablation of renal tumors. Ablation of renal lesions near the psoas muscle
      may result in paresthesia in the distribution of the genitofemoral nerve. The
      present report describes a case of sensory and muscular dysfunction after RF
      ablation of a renal lesion lying on top of the psoas muscle that was treated
      without hydrodissection. To prevent this complication, hydrodissection was
      effectively used in two other patients during RF ablation of lesions abutting or
      in close proximity to the psoas muscle.

PMID- 17185696
TI  - Vascular smooth muscle cell apoptosis induced by "supercooling" and rewarming.
AB  - PURPOSE: The underlying mechanisms for the reduction in restenosis caused by
      cryoplasty for peripheral atherosclerotic lesions are not well understood.
      Because vascular smooth muscle cells (SMCs) are known to play a critical role in
      restenosis and neointimal hyperplasia, the aim of this study was to determine SMC
      survival under conditions of "supercooling" and/or rewarming. MATERIALS AND
      METHODS: Bovine aortic SMCs were supercooled to -10 degrees C for 0, 60, or 120
      seconds with a custom-designed conduction cooling stage and then rewarmed to 37
      degrees C in an incubator for 0, 12, or 24 hours. A terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling assay was used to measure the degree
      of apoptosis. Activation of Akt (ie, protein kinase B), a key signal protein
      involved in cell survival, was assessed by Western blot analysis. RESULTS: An
      increase in apoptotic SMCs was observed with increasing supercooling and
      rewarming time. Akt was significantly activated at only the most severe condition
      (120 seconds of supercooling and 24 hours of rewarming), which showed a 2.03-fold
      increase compared with the group without rewarming. CONCLUSIONS: The data suggest
      that SMC apoptosis occurs with supercooling and rewarming. Protective cell
      survival mechanisms were activated only late in the rewarming phase. This may
      partially explain the long-term patency observed with cryoplasty of
      atherosclerotic peripheral lesions.

PMID- 17185697
TI  - Analysis of simulated angiographic procedures: part 1--capture and presentation
      of audio and video recordings.
AB  - PURPOSE: To assess different methods of recording angiographic simulations and to
      determine how such recordings might be used for training and research. MATERIALS
      AND METHODS: Two commercially available high-fidelity angiography simulations,
      the Mentice Vascular Interventional Simulation Trainer and the Simbionix
      AngioMentor, were used for data collection. Video and audio records of simulated
      procedures were created by different methods, including software-based screen
      capture, video splitters and converters, and external cameras. Recording
      parameters were varied, and the recordings were transferred to computer
      workstations for postprocessing and presentation. RESULTS: The information
      displayed on the simulators' computer screens could be captured by each method.
      Although screen-capture software provided the highest resolution, workflow
      considerations favored a hardware-based solution that duplicated the video signal
      and recorded the data stream(s) at lower resolutions. Additional video and audio
      recording devices were used to monitor the angiographer's actions during the
      simulated procedures. The multiple audio and video files were synchronized and
      composited with personal computers equipped with commercially available video
      editing software. Depending on the needs of the intended audience, the resulting
      files could be distributed and displayed at full or reduced resolutions.
      CONCLUSIONS: The capture, editing, presentation, and distribution of synchronized
      multichannel audio and video recordings holds great promise for angiography
      training and simulation research. To achieve this potential, technical challenges
      will need to be met, and content will need to be tailored to suit the needs of
      trainees and researchers.

PMID- 17185698
TI  - Radiofrequency ablation of normal lungs after pulmonary artery embolization with
      use of degradable starch microspheres: results in a porcine model.
AB  - PURPOSE: The present study was performed to evaluate the effect of pulmonary
      artery embolization on radiofrequency (RF) ablation of normal porcine lungs.
      MATERIALS AND METHODS: RF ablation zones (n=34) were created in the normal lungs
      of five domestic pigs (five zones in each of the first two pigs and eight zones
      in each of the remaining three pigs) with an expandable multitined electrode with
      use of bilateral thoracotomy. RF ablation was performed without pulmonary artery
      embolization (group 1, n=8), immediately after embolization (group 2, n=11), 15
      minutes after embolization (group 3, n=7), and 30 minutes after embolization
      (group 4, n=8) with degradable starch microspheres. Among them, 12 ablation zones
      were excluded from this study because they were considerably limited by the
      presence of the pleura or large bronchi. The remaining 22 zones were included
      (n=7, n=5, n=4, and n=6 in groups 1, 2, 3, and 4, respectively). Coagulation
      necrosis volumes in the ablation zones were measured and compared among the
      groups. RESULTS: Coagulation necrosis volumes were 0.9+/-0.5 cm3, 2.1+/-0.4 cm3,
      2.1+/-1.0 cm3, and 1.9+/-0.6 cm3 in groups 1, 2, 3, and 4, respectively. Groups 2
      4 showed significantly larger coagulation volumes than group 1 (P=.012, P=.023,
      and P=.010 in groups 2, 3, and 4, respectively). CONCLUSION: Pulmonary artery
      embolization contributed to larger volumes of coagulation necrosis after RF
      ablation of normal lungs.

PMID- 17185699
TI  - CT fluoroscopy shielding: decreases in scattered radiation for the patient and
      operator.
AB  - PURPOSE: High-radiation exposure occurs during computed tomographic (CT)
      fluoroscopy. Patient and operator doses during thoracic and abdominal
      interventional procedures were studied in the present experiment, and a novel
      shielding device to reduce exposure to the patient and operator was evaluated.
      MATERIALS AND METHODS: With a 16-slice CT scanner in CT fluoroscopy mode (120
      kVp, 30 mA), surface dosimetry was performed on adult and pediatric phantoms. The
      shielding was composed of tungsten antimony in the form of a lightweight polymer
      sheet. Doses to the patient were measured with and without shielding for thoracic
      and abdominal procedures. Doses to the operator were recorded with and without
      phantom, gantry, and table shielding in place. Double-layer lead-free gloves were
      used by the operator during the procedures. RESULTS: Tungsten antimony shielding
      adjacent to the scan plane resulted in a maximum dose reduction of 92.3% to the
      patient. Maximum 85.6%, 93.3%, and 85.1% dose reductions were observed for the
      operator's torso, gonads, and hands, respectively. The use of double-layer lead
      free gloves resulted in a maximum radiation dose reduction of 97%. CONCLUSIONS:
      Methods to reduce exposure during CT fluoroscopy are effective and should be
      searched for. Significant reduction in radiation doses to the patient and
      operator can be accomplished with tungsten antimony shielding.

PMID- 17185700
TI  - Stereotactic technique of catheter placement in the stump of the superior vena
      cava in children with impaired venous access.
AB  - The long-term survival of children with irreversible intestinal failure is often
      dependent on adequate central venous access for the administration of parenteral
      nutrition. In children with occlusion of major central thoracic veins, innovative
      techniques to establish venous access have been described in the literature. The
      present report describes an innovative stereotactic technique of catheter
      insertion in children with occluded internal jugular and brachiocephalic veins.
      The catheter is inserted percutaneously from the neck into the distal patent
      stump of the superior vena cava communicating with the right atrium.

PMID- 17185701
TI  - Use of angioplasty balloon-assisted Seldinger technique for complicated small
      vessel catheterization.

PMID- 17185702
TI  - Intravascular migration of a Schon tunneled hemodialysis catheter anchoring hub.

PMID- 17185703
TI  - Scrooge and intellectual property rights.

PMID- 17185704
TI  - Shooting down the NHS reform track.

PMID- 17185705
TI  - What stays constant at the heart of medicine.

PMID- 17185706
TI  - Mistletoe as a treatment for cancer.

PMID- 17185707
TI  - How Web 2.0 is changing medicine.

PMID- 17185708
TI  - Sword swallowing and its side effects.
AB  - OBJECTIVE: To evaluate information on the practice and associated ill effects of
      sword swallowing. DESIGN: Letters sent to sword swallowers requesting information
      on technique and complications. SETTING: Membership lists of the Sword
      Swallowers' Association International. PARTICIPANTS: 110 sword swallowers from 16
      countries. RESULTS: We had information from 46 sword swallowers. Major
      complications are more likely when the swallower is distracted or swallows
      multiple or unusual swords or when previous injury is present. Perforations
      mainly involve the oesophagus and usually have a good prognosis. Sore throats are
      common, particularly while the skill is being learnt or when performances are too
      frequent. Major gastrointestinal bleeding sometimes occurs, and occasional chest
      pains tend to be treated without medical advice. Sword swallowers without
      healthcare coverage expose themselves to financial as well as physical risk.
      CONCLUSIONS: Sword swallowers run a higher risk of injury when they are
      distracted or adding embellishments to their performance, but injured performers
      have a better prognosis than patients who suffer iatrogenic perforation.

PMID- 17185709
TI  - You're not going to give me the umbrella, are you?

PMID- 17185710
TI  - Why Danes are smug: comparative study of life satisfaction in the European Union.

PMID- 17185711
TI  - Phenotypic differences between male physicians, surgeons, and film stars:
      comparative study.
AB  - OBJECTIVES: To test the hypothesis that, on average, male surgeons are taller and
      better looking than male physicians, and to compare both sets of doctors with
      film stars who play doctors on screen. DESIGN: Comparative study. SETTING:
      Typical university hospital in Spain, located in Barcelona and not in a sleepy
      backwater. PARTICIPANTS: Random sample of 12 surgeons and 12 physicians plus 4
      external controls (film stars who play doctors), matched by age (50s) and sex
      (all male). INTERVENTIONS: An independent committee (all female) evaluated the
      "good looking score" (range 1-7). MAIN OUTCOME MEASURES: Height (cm) and points
      on the good looking score. RESULTS: Surgeons were significantly taller than
      physicians (mean height 179.4 v 172.6 cm; P=0.01). Controls had significantly
      higher good looking scores than surgeons (mean score 5.96 v 4.39; difference
      between means 1.57, 95% confidence interval 0.69 to 2.45; P=0.013) and physicians
      (5.96 v 3.65; 2.31, 1.58 to 3.04; P=0.003). Surgeons had significantly higher
      good looking scores than physicians (4.39 v 3.65; 0.74; 0.25 to 1.23; P=0.010).
      CONCLUSIONS: Male surgeons are taller and better looking than physicians, but
      film stars who play doctors on screen are better looking than both these groups
      of doctors. Whether these phenotypic differences are genetic or environmental is
      unclear.

PMID- 17185712
TI  - Subcutaneous inflammation mimicking metastatic malignancy induced by injection of
      mistletoe extract.

PMID- 17185713
TI  - Time to stop sniffing the air: snapshot survey.
AB  - OBJECTIVE: To determine whether the phrase "sniffing the morning air" is useful
      in positioning patients for tracheal intubation. DESIGN: Snapshot survey.
      SETTING: Teaching hospital. PARTICIPANTS: 21 anaesthetists. MAIN OUTCOME
      MEASURES: Angles of neck, line of sight, and hip to shoulder, as measured on a
      photograph. RESULTS: Angles ranged widely, especially line of sight: 7 degrees 
      37 degrees with horizontal. CONCLUSIONS: As patients are positioned supine,
      rather than standing, the phrase is unhelpful; an explicit description of head
      position would be better.

PMID- 17185714
TI  - The ideal tool for decorators: a novel use for disposable laryngoscope blades.

PMID- 17185715
TI  - The mysterious death of Francesco I de' Medici and Bianca Cappello: an arsenic
      murder?

PMID- 17185717
TI  - Maggie's Centres.

PMID- 17185716
TI  - "Veterinary" diagnosis of lead poisoning in pregnancy.

PMID- 17185718
TI  - Another reason for opening access to research.

PMID- 17185719
TI  - Startling technologies promise to transform medicine.

PMID- 17185720
TI  - Back to the future: how good are doctors at gazing in the crystal ball?

PMID- 17185721
TI  - Searching historical herbal texts for potential new drugs.

PMID- 17185722
TI  - Getting new drugs to market: how individuals could do this without leaving their
      desks.

PMID- 17185723
TI  - Sir Victor Horsley--an inspiration.

PMID- 17185724
TI  - Better evidence, improved care.

PMID- 17185726
TI  - The joy of discovery.

PMID- 17185727
TI  - Given the chance I'd start all over again.

PMID- 17185728
TI  - Living conditions.

PMID- 17185729
TI  - The challenging isle: a walk through Soho.

PMID- 17185730
TI  - Sri Lankan sanni masks: an ancient classification of disease.

PMID- 17185732
TI  - Daisy the Doctor, Dr Dose, Dr Grizzly, Dr Amelia Bedelia, and colleagues.

PMID- 17185731
TI  - From a 16th century monastery to a 21st century orthopaedic hospital.

PMID- 17185733
TI  - Physicians in opera--reflection of medical history and public perception.

PMID- 17185734
TI  - Faints, fits, and fatalities from emotion in Shakespeare's characters: survey of
      the canon.
AB  - OBJECTIVES: To determine how often Shakespeare's characters faint, fit, or die
      from extreme emotion; to assess Shakespeare's uniqueness in this regard; and to
      examine the plausibility of these dramatised events. DESIGN: Line by line search
      through modern editions of these late 16th and early 17th century works for
      accounts of characters fainting, fitting, or dying while under strong emotion and
      for no other apparent reason. DATA SOURCES: All 39 canonical plays by Shakespeare
      and his three long narrative poems; 18 similar works by seven of Shakespeare's
      best known contemporaries. RESULTS: 10 deaths from strong emotion are recorded by
      Shakespeare (three occur on stage); all are due to grief, typically at the loss
      of a loved one. All but two of the deaths are in the playwright's late works.
      Some deaths are sudden. Another 29 emotion induced deaths are mentioned as
      possible, but the likelihood of some can be challenged. Transient loss of
      consciousness is staged or reported in 18 cases (sounding like epilepsy in two)
      and near fainting in a further 13. Extreme joy is sometimes depicted as a factor
      in these events. Emotional death and fainting also occur occasionally in works by
      Shakespeare's contemporaries. CONCLUSIONS: These dramatic phenomena are part of
      the early modern belief system but are also plausible by modern understanding of
      physiology and disease. They teach us not to underestimate the power of the
      emotions to disturb bodily functions.

PMID- 17185735
TI  - The night Bernard Shaw taught us a lesson.

PMID- 17185737
TI  - Drought-adaptive traits derived from wheat wild relatives and landraces.
AB  - Exotic parents are being used to increase allelic diversity in bread wheat
      breeding through (i) interspecific hybridization of the ancestral genomes to
      produce so-called synthetic derived (SYN-DER) wheat, and (ii) crossing with
      landrace accessions, originating in abiotically stressed environments, that have
      become isolated from mainstream gene pools. Evaluation of the inherent genetic
      diversity encompassed by drought-adapted landraces compared with checks using DNA
      fingerprinting confirmed that some landraces were not only distant from checks
      but also showed significant diversity among each other. Improvement in
      performance of SYN-DER lines compared with recurrent parents was not associated
      with a larger overall investment in root dry weight, but rather an increased
      partitioning of root mass to deeper soil profiles (between 60 cm and 120 cm) and
      increased ability to extract moisture from those depths. The best Mexican
      landraces showed superior ability in terms of water extraction from soil depth,
      as well as increased concentration of soluble carbohydrates in the stem shortly
      after anthesis. Although it can be argued that inferring theoretical yield gains
      from the over-expression of any of these traits is questionable, since
      compensatory mechanisms may be at work, the fact remains that mechanistic or
      genetic linkages among physiological traits remain largely un-established. In the
      meantime, trait information is being used to make strategic crosses based on the
      theoretical combination of useful stress-adaptive traits with the possibility of
      realizing additive gene action in selected progeny. Candidates for crossing with
      elite check cultivars include landraces identified that showed relatively high
      biomass under drought combined with favourable expression of physiological traits
      such as stem carbohydrates, water extraction characteristics, and transpiration
      efficiency.

PMID- 17185736
TI  - Transcriptional control of anthocyanin biosynthetic genes in the Caryophyllales.
AB  - Anthocyanins and betacyanins, two types of red pigment, have never been found to
      occur together in plants. Although anthocyanins are widely distributed in higher
      plants, betacyanins have replaced anthocyanins in the Caryophyllales. The
      accumulation of flavonols in the Caryophyllales suggests that the step(s) of
      anthocyanin biosynthesis from dihydroflavonols to anthocyanins could be blocked
      in the Caryophyllales. Dihydroflavonol 4-reductase (DFR) and anthocyanidin
      synthase (ANS) cDNAs were isolated from plants of the Caryophyllales. An enzyme
      activity assay showed that the Caryophyllales possess functional DFR and ANS. The
      expression profile revealed that DFR and ANS are not expressed in most tissues
      and organs except the seeds in Spinacia oleracea. Here, the promoter regions of
      DFR and ANS were isolated from S. oleracea. Analysis of DFR and ANS promoter
      sequences revealed several putative transcriptional factor-binding motifs. A
      yeast one-hybrid assay showed that Petunia hybrida AN2 (PhAN2) and JAF13
      (PhJAF13), which were the regulators of anthocyanin synthesis in P. hybrida,
      could bind to the S. oleracea DFR and ANS promoters. However, the transient assay
      in Phytolacca americana cell cultures and leaves of S. oleracea showed that the
      promoters were not activated by ectopic expression of PhAN2 and PhJAF13, while
      the DFR and ANS promoters of Arabidopsis thaliana, an anthocyanin-producing
      species, were activated. One possible explanation for the lack of anthocyanins in
      the Caryophyllales is the difference in the promoter regions of DFR and ANS
      compared with those of anthocyanin-producing species.

PMID- 17185738
TI  - Unique properties of NADP-thioredoxin reductase C in legumes.
AB  - NADP-thioredoxin reductases (NTRs) reduce thioredoxins (Trxs), using NADPH as a
      reductant, together constituting complete redox systems (NTS). Beside NTRA and
      NTRB targeted to both cytosol and mitochondria of plant cells, there is in
      chloroplasts an unusual NTR (NTRC) harbouring a Trx domain in a C-terminal
      extension, as recently reported in Oryza sativa. Although NTRC may constitute a
      complete NTS, it was described as a bifunctional enzyme. Because the gene is only
      present in photosynthetic organisms and the protein in green tissues, NTRC was
      thought to have a role restricted to photosynthetic cells. To determine whether
      NTRC from dicot plants is a bifunctional enzyme or a complete NTS, as well as to
      identify its putative target, NTRC from Medicago truncatula was cloned and NTRA
      was cloned for comparison. Here evidence is presented that MtNTRC (i) acts as an
      NTS and reduces dithiobisnitrobenzoate (DTNB) with a turnover (0.62 s(-1))
      similar to that measured with MtNTRA in the presence of a Trxh (0.81 s(-1)); (ii)
      is able to use both NADPH (k(M)=2.4 microM) and NADH (k(M)=11 microM) as
      cofactors; (iii) efficiently reduces BAS1, a plastidial peroxiredoxin; and (iv)
      is expressed in both leaves and stems but unexpectedly is even more abundant in
      cotyledons from dry and germinating seeds. Because BAS1 is also present in both
      green tissues and seeds, NTRC/BAS1 may be involved in the scavenging of peroxides
      produced in green tissues during the day or the night and in seeds during
      germination. These results suggest different roles for NTRC in monocot and dicot
      plants.

PMID- 17185739
TI  - Patterns and kinetics of water uptake by soybean seeds.
AB  - Soybean [Glycine max (L.) Merr.] plants produce some seeds (called stone or
      impermeable seeds) that do not take up water for long periods of time. The
      present investigation confirmed that the stone seed trait is a feature of the
      seed coat: isolated embryos from both stone and permeable seeds took up water
      equally quickly. A whole, permeable seed typically imbibed water initially
      through its dorsal side, forming wrinkles in the seed coat and delivering water
      to the underlying cotyledons. Later, some lateral movement of water through the
      coat occurred, presumably through the air spaces of the osteosclereid layer.
      Imbibition by seeds was a two-phase process, the first dominated by hydration of
      the seed coat and the second by hydration of the cotyledons, which was rate
      limited by the coat. When hydrated, coats of stone seeds were permeable to water
      but their hydraulic conductivity, as measured with a pressure probe, was smaller
      than that of coats from permeable seeds by a factor of five. Hydrated coats of
      both permeable and stone seeds showed weak osmometer properties.

PMID- 17185740
TI  - Differential feedback regulation of ethylene biosynthesis in pulp and peel
      tissues of banana fruit.
AB  - The feedback regulation of ethylene biosynthesis in banana [Musa sp. (AAA group,
      Cavendish subgroup) cv. Grand Nain] fruit was investigated in an attempt to
      clarify the opposite effect of 1-methylcyclopropene (1-MCP), an ethylene action
      inhibitor, before and after the onset of ripening. 1-MCP pre-treatment completely
      prevented the ripening-induced effect of propylene in pre-climacteric banana
      fruit, whereas treatment after the onset of ripening stimulated ethylene
      production. In pre-climacteric fruit, higher concentrations of propylene
      suppressed ethylene production more strongly, despite their earlier ethylene
      inducing effect. Exposure of the fruit ripened by propylene to 1-MCP increased
      ethylene production concomitantly with an increase in 1-aminocyclopropane-1
      carboxylate (ACC) synthase activity and ACC content, and prevented a transient
      decrease in MA-ACS1 transcripts in the pulp tissues. In contrast, in the peel of
      ripening fruit, 1-MCP prevented the increase in ethylene production and
      subsequently the ripening process by reduction of the increase in MA-ACS1 and MA
      ACO1 transcripts and of ACC synthase and ACC oxidase activities. These results
      suggest that ethylene biosynthesis in ripening banana fruit may be controlled
      negatively in the pulp tissue and positively in the peel tissue. This
      differential regulation by ethylene in pulp and peel tissues was also observed
      for MA-PL, MA-Exp, and MA-MADS genes.

PMID- 17185742
TI  - The V-ATPase from etiolated barley (Hordeum vulgare L.) shoots is activated by
      blue light and interacts with 14-3-3 proteins.
AB  - The vacuolar H(+)-ATPase (V-ATPase) is a key enzyme that controls the
      electrochemical proton potential across endomembranes. Although evidence suggests
      that V-ATPase is important for photo-morphogenesis, little is known about short
      term regulation of V-ATPase upon initiation of the photo-morphogenetic programme
      by exposure of dark-grown plants to light. In this study, etiolated coleoptiles
      were given a short blue light treatment and V-ATPase characteristics were
      determined. The effectiveness of the light treatment was assessed by means of
      fusicoccin binding to the plasma membrane; this increased 5-fold. The short light
      treatment also induced a 2-fold to 3-fold increase in the hydrolytic activity of
      V-ATPase. Members of the 14-3-3 protein family are involved in both blue light
      perception and the subsequent activation of the P-type ATPase. We provide
      evidence that 14-3-3 proteins specifically interact with the catalytic A-subunit
      of the V-ATPase. First, the isolated V1-part of the V-ATPase co-purifies with 14
      3-3 on a gel filtration column. Secondly, in an overlay experiment, 14-3-3
      interacts with a 68 kDa band that was identified as the V1 A-subunit by mass
      spectrometry. Thirdly, in 14-3-3 affinity chromatography, both A- and B-subunits
      of the catalytic moiety of the V-ATPase were identified by matrix-assisted laser
      desorption ionization tandem time of flight mass spectrometry (MALDI TOF/TOF MS)
      as 14-3-3-interacting proteins. It was shown that the A-subunit can be
      phosphorylated in vitro by a tonoplast-bound kinase, whose properties are
      affected by blue light. Taken together, the data show that besides the P- and F
      type H(+)-ATPases, the V-type H(+)-ATPase also interacts with 14-3-3 proteins.

PMID- 17185741
TI  - Involvement of rapid nucleotide synthesis in recovery from phosphate starvation
      of Catharanthus roseus cells.
AB  - Growth of suspension-cultured Catharanthus roseus cells ceased during phosphate
      starvation, but the cells grew again upon addition of Pi even after long-term
      starvation. The metabolic fate of [(33)P]Pi was studied in 1-week-old stationary
      phase cells in ordinary culture and in 1- or 2-week-old Pi-starved cells.
      Immediately after administration, the most heavily labelled organic compounds are
      nucleotides, followed by sugar phosphates. Two weeks Pi starvation slowed down
      the speed of incorporation of (33)P into nucleotides. The RNA, protein, and free
      nucleotide content all decreased gradually during Pi starvation; however, these
      compounds, especially nucleotides, increased markedly in the 24 h after addition
      of Pi. These responses are found in all cells examined, although the total
      amounts of these compounds were lower in the long-term Pi-deficient cells. Of the
      nucleotides, a marked increase was observed in nucleoside triphosphates and UDP
      glucose. The transcript level of phosphate transporter and the activities of acid
      phosphatase, 5'- and 3'-nucleotidase, and adenosine nucleosidase were all reduced
      by the addition of Pi. In contrast, the activities of adenine
      phosphoribosyltransferase, nicotinate phosphoribosyltransferase, and
      nicotinamidase, which are salvage enzymes of purine and pyridine nucleotides,
      were markedly increased in the Pi-fed cells. Little or no increase was observed
      in adenosine kinase. In the light of these results, the possible involvement of
      net nucleotide synthesis in the initial metabolic events of recovery from Pi
      deficiency are discussed.

PMID- 17185743
TI  - Primary central nervous system lymphoma treated with high-dose methotrexate, high
      dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted
      whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe
      Hamato-Onkologie OSHO-53 phase II study.
AB  - BACKGROUND: We investigated the efficacy and safety of tandem high-dose
      methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT)
      with autologous peripheral blood stem-cell transplantation (aPBSCT) and response
      adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed
      primary central nervous system lymphoma. PATIENTS AND METHODS: Twenty-three
      patients were treated with HD-MTX on days 1 and 10. In case of at least a partial
      remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response
      to induction or without complete remission (CR) after HD-BuTT received WBRT.
      RESULTS: Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of
      69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three
      deaths during therapy. With longer follow-up three neurotoxic deaths occurred in
      irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD
      BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69)
      median event-free survival (EFS) and overall survival (OS) for all patients were
      17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached",
      respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients
      versus 56% and 61% for the HD-BuTT group, respectively. CONCLUSION: MTX induction
      followed by HD-BuTT is an effective and very short time-on-treatment regimen.
      Median survival for patients treated with high-dose chemotherapy is not reached
      yet. The induction regimen needs optimisation. In this study WBRT was associated
      with a high incidence of severe neurotoxicity.

PMID- 17185744
TI  - Treatment of anthracycline extravasation with Savene (dexrazoxane): results from
      two prospective clinical multicentre studies.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy and tolerability
      of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy
      verified anthracycline extravasation. PATIENTS AND METHODS: Two prospective, open
      label, single-arm, multicentre studies in patients with anthracycline
      extravasation were carried out. Patients with fluorescence-positive tissue
      biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and
      500 mg/m(2)) starting no later than 6 h after the incident. Patients were
      assessed for efficacy (the possible need for surgical resection) and toxicity
      during the treatment period and regularly for the next 3 months. RESULTS: In 53
      of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery
      requiring necrosis. One patient (1.8%) required surgical debridement. Thirty
      eight patients (71%) were able to continue their scheduled chemotherapy without
      postponement. Twenty-two patients (41%) experienced hospitalisation due to the
      extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine
      patients; 17%) were the most frequent sequelae. Haematologic toxicity was common
      as expected from the fact that the extravasation occurred during a chemotherapy
      course. Other toxic effects were transient elevation of alanine
      aminotransferases, nausea, and local pain at the dexrazoxane injection site.
      CONCLUSION: Dexrazoxane proved to be an effective and well-tolerated acute
      treatment with only one out of 54 assessable patients requiring surgical
      resection (1.8%).

PMID- 17185745
TI  - Gene cluster analysis method identifies horizontally transferred genes with high
      reliability and indicates that they provide the main mechanism of operon gain in
      8 species of gamma-Proteobacteria.
AB  - The formation mechanism of operons remains unresolved: operons may form by
      rearrangements within a genome or by acquisition of genes from other species,
      that is, horizontal gene transfer (HGT). One hindrance to its elucidation is the
      unavailability of a method to accurately identify HGT, although it is generally
      considered to occur. It is critically important first to select horizontally
      transferred (HT) genes reliably and then to determine the extent to which HGT is
      involved in operon formation. For this purpose, we considered indels in terms of
      gene clusters instead of individual genes and chose candidates of HT genes in 8
      species of Escherichia, Shigella, and Salmonella based on the minimization of
      indels. To select a benchmark set of positively HT genes against which we can
      evaluate the candidate set, we devised another procedure using intergenetic
      alignments. Comparison with the benchmark set demonstrated the absence of a
      significant number of false positives in the candidate set, showing the high
      reliability of the method. Analyses of Escherichia coli K-12 operons revealed
      that although approximately 20 operons were probably gained from the last common
      ancestor of the 8 gamma-proteobacteria, deletion of intervening genes accounts
      for the formation of no operons, whereas horizontal transfer expanded 2 operons
      and introduced 4 entire operons. Based on these observations and reasoning, we
      suggest that the main mechanism of operon gain is HGT rather than intragenomic
      rearrangements. We propose that genes with related essential functions tend to
      reside in conserved operons, whereas genes in nonconserved operons mostly confer
      slight advantage to the organisms and frequently undergo horizontal transfer and
      decay. HT genes constitute at least 5.5% of the genes in the 8 species and
      approximately 45% of which originate from other gamma-proteobacteria. Genes
      involved in viral functions and mobile and extrachromosomal element functions are
      HT more often than expected. This finding indicates frequent mediation of HGT by
      bacteriophages. On the other hand, not only informational genes (those involved
      in transcription, translation, and related processes) but also operational genes
      (those involved in housekeeping) are HT less frequently than expected.

PMID- 17185746
TI  - Docosahexaenoic acid and arachidonic acid are fundamental supplements for the
      induction of neuronal differentiation.
AB  - Cell replacement therapy is being investigated for the treatment of
      neurodegenerative disorders. Adult autologous bone marrow-derived mesenchymal
      stem cells (MSCs) have been induced to differentiate into neuron-like cells
      harboring a variety of neuronal markers and transcription factors. Neural tissue
      characteristically contains high proportions of docosahexaenoic acid (DHA) and
      arachidonic acid (AA). In this study, evaluation of the fatty acid profile of
      differentiated neuron-like cells revealed a very low level of DHA, similar to
      that in MSCs but different from typical neurons. Supplementation of the medium
      with DHA alone resulted in increased levels of DHA but concomitant low levels of
      AA. However, supplementation with both DHA and AA yielded a fatty acid profile
      resembling that of neural tissue. It also resulted in enhanced outgrowth of
      neurite-like processes, hallmarks of neuronal differentiation. These findings
      demonstrate the essentiality of DHA and AA supplementation in the process of
      induced neuronal differentiation and have important implications for the
      development of cell replacement strategies of neural repair.

PMID- 17185747
TI  - Use of gene expression profiling to identify a novel glucocorticoid sensitivity
      determining gene, BMPRII.
AB  - Wide variation in glucocorticoid (Gc) sensitivity exists between individuals
      which may influence susceptibility to, and treatment response of, inflammatory
      diseases. To determine a genetic fingerprint of Gc sensitivity 100 healthy human
      volunteers were polarized into the 10% most Gc-sensitive and 10% most Gc
      resistant following a low dose dexamethasone (0.25 mg) suppression test. Gene
      expression profiling of primary lymphocytes identified the 98 most significantly
      Gc regulated genes. These genes were used to build a subnetwork of Gc signaling,
      with 54 genes mapping as nodes, and 6 non-Gc regulated genes inferred as
      signaling nodes. Twenty four of the 98 genes showed a difference in Gc response
      in vitro dependent on the Gc sensitivity of their donor individuals in vivo. A
      predictive model was built using both partial least squares discriminate analysis
      and support vector machines that predicted donor glucocorticoid sensitivity with
      87% accuracy. Discriminating genes included bone morphogenetic protein receptor,
      type II (BMPRII). Transfection studies showed that BMPRII modulated Gc action.
      These studies reveal a broad base of gene expression that predicts Gc sensitivity
      and determine a Gc signaling network in human primary T lymphocytes. Furthermore,
      this combined gene profiling, and functional analysis approach has identified
      BMPRII as a modulator of Gc signaling.

PMID- 17185748
TI  - Regulation of Kv1 channel trafficking by the mamba snake neurotoxin dendrotoxin
      K.
AB  - Modulation of voltage-gated potassium (Kv) channel surface expression can
      profoundly affect neuronal excitability. Some, but not all, mammalian Shaker or
      Kv1 alpha subunits contain a dominant endoplasmic reticulum (ER) retention signal
      in their pore region, preventing surface expression of Kv1.1 homotetrameric
      channels and of heteromeric Kv1 channels containing more than one Kv1.1 subunit.
      The critical amino acid residues within this ER pore-region retention signal are
      also critical for high-affinity binding of snake dendrotoxins (DTX). This
      suggests that ER retention may be mediated by an ER protein with a domain
      structurally similar to that of DTX. One facet of such a model is that expression
      of soluble DTX in the ER lumen should compete for binding to the retention
      protein and allow for surface expression of retained Kv1.1. Here, we show that
      luminal DTX expression dramatically increased both the level of cell surface
      Kv1.1 immunofluorescence staining and the proportion of Kv1.1 with processed N
      linked oligosaccharides. Electrophysiological analyses showed that luminal DTX
      expression led to significant increases in Kv1.1 currents. Together, these data
      showed that luminal DTX expression increases surface expression of functional
      Kv1.1 homotetrameric channels and support a model whereby a DTX-like ER protein
      regulates abundance of cell surface Kv1 channels.

PMID- 17185749
TI  - T-cell inactivation and immunosuppressive activity induced by HIV gp41 via novel
      interacting motif.
AB  - Fusion peptide (FP) of the HIV gp41 molecule inserts into the T cell membrane
      during virus-cell fusion. FP also blocks the TCR/CD3 interaction needed for
      antigen-triggered T cell activation. Here we used in vitro (fluorescence and
      immunoprecipitation), in vivo (T cell mediated autoimmune disease adjuvant
      arthritis), and in silico methods to identify the FP-TCR novel interaction motif:
      the alpha-helical transmembrane domain (TMD) of the TCR alpha chain, and the beta
      sheet 5-13 region of the 16 N-terminal aa of FP (FP(1-16)). Deciphering the
      molecular mechanism of the immunosuppressive activity of FP provides a new
      potential target to overcome the immunosuppressant activity of HIV, and in
      addition a tool for down-regulating immune mediated inflammation.

PMID- 17185751
TI  - Neuropilin-1 and neuropilin-2 enhance VEGF121 stimulated signal transduction by
      the VEGFR-2 receptor.
AB  - The neuropilin-1 (np1) receptor binds the 165 amino-acid form of vascular
      endothelial growth factor165 (VEGF165) and functions as an enhancer that
      potentiates VEGF165 signaling via the VEGFR-2 tyrosine-kinase receptor. To study
      the mechanism by which neuropilins potentiate VEGF activity we produced a VEGF165
      mutant (VEGF165KF) that binds to neuropilins but displays a much lower affinity
      toward VEGFR-1 and VEGFR-2. VEGF165KF failed to induce VEGFR-2 phosphorylation in
      cells lacking neuropilins. However, in the presence of np1, VEGF165KF bound
      weakly to VEGFR-2, induced VEGFR-2 phosphorylation, and activated ERK1/2.
      Interestingly, VEGF165KF did not promote formation of VEGFR-2/np1 complexes nor
      did high concentrations of VEGF165KF inhibit VEGF165 induced formation of such
      complexes, suggesting that VEGF165 does not stabilize VEGFR-2/np1 complexes by
      forming bridges spanning VEGFR-2 and np1. VEGF121 is a VEGF form that does not
      bind to neuropilins. Surprisingly, both np1 and neuropilin-2 (np2) enhanced
      VEGF121-induced phosphorylation of VEGFR-2 and VEGF121-induced proliferation of
      endothelial cells. The enhancement of VEGF121 activity by np1 was accompanied by
      a 10-fold increase in binding affinity to VEGFR-2 and was not associated with the
      formation of new VEGFR-2/np1 complexes. These observations suggest that
      neuropilins enhance the activity of VEGF forms that do not bind to neuropilins,
      indicate that np2 is a functional VEGF receptor, and imply that spontaneously
      formed VEGFR-2/np1 complexes suffice for efficient neuropilin mediated
      enhancement of VEGF activity.

PMID- 17185750
TI  - AHNAK, a novel component of the dysferlin protein complex, redistributes to the
      cytoplasm with dysferlin during skeletal muscle regeneration.
AB  - Mutations in dysferlin cause limb girdle muscular dystrophy 2B, Miyoshi myopathy
      and distal anterior compartment myopathy. Dysferlin is proposed to play a role in
      muscle membrane repair. To gain functional insight into the molecular mechanisms
      of dysferlin, we have searched for dysferlin-interacting proteins in skeletal
      muscle. By coimmunoprecipitation coupled with mass spectrometry, we demonstrate
      that AHNAK interacts with dysferlin. We defined the binding sites in dysferlin
      and AHNAK as the C2A domain in dysferlin and the carboxyterminal domain of AHNAK
      by glutathione S-transferase (GST)-pull down assays. As expected, the N-terminal
      domain of myoferlin also interacts with the carboxyterminal domain of AHNAK. In
      normal skeletal muscle, dysferlin and AHNAK colocalize at the sarcolemmal
      membrane and T-tubules. In dysferlinopathies, reduction or absence of dysferlin
      correlates with a secondary muscle-specific loss of AHNAK. Moreover, in
      regenerating rat muscle, dysferlin and AHNAK showed a marked increase and
      cytoplasmic localization, consistent with the direct interaction between them.
      Our data suggest that dysferlin participates in the recruitment and stabilization
      of AHNAK to the sarcolemma and that AHNAK plays a role in dysferlin membrane
      repair process. It may also have significant implications for understanding the
      biology of AHNAK-containing exocytotic vesicles, "enlargosomes," in plasma
      membrane remodeling and repair.

PMID- 17185752
TI  - Truncated isoform of mouse alphaT-catenin is testis-restricted in expression and
      function.
AB  - AlphaT-catenin is a recently identified member of the alpha-catenin family of
      cell-cell adhesion molecules. For decades it was thought that alpha-catenins
      mediate solid cell-cell adhesion by linking the cadherin-mediated cell-cell
      adhesion complex with the actin cytoskeleton. However, the roles of alpha
      catenins in this classical adhesion model have been questioned recently. AlphaT
      catenin has a restricted expression pattern, in contrast to the ubiquitously
      expressed alphaE-catenin. High levels of alphaT-catenin were detected in heart
      and testis. Northern and Western blot experiments indicated that besides the
      standard full-length alphaT-catenin transcript, smaller alternative transcripts
      are expressed in testis. We report the cloning of two alternative transcripts of
      the mouse alphaT-catenin gene (transcript-B and -X), both of which are expressed
      in a testis-restricted manner from two putative alternative promoters.
      Alternative transcript-X encodes a smaller protein, isoform-X, which lacks the
      amino-terminal beta-catenin binding domain of the standard mouse alphaT-catenin
      protein, and is therefore unable to restore cell-cell adhesion in an alpha
      catenin-negative colon carcinoma cell line. Immunohistochemical analysis showed
      specific localization of the alphaT-catenin isoform-X in the differentiating germ
      cells. In contrast to the standard full-length alphaT-catenin protein, this
      shortened isoform-X can bind to l-afadin, an important component of the
      nectin/afadin/ponsin adhesion complex that reportedly is essential for
      spermatogenesis.

PMID- 17185753
TI  - The history of pyrosequencing.
AB  - One late afternoon in the beginning of January 1986, bicycling from the lab over
      the hill to the small village of Fullbourn, the idea for an alternative DNA
      sequencing technique came to my mind. The basic concept was to follow the
      activity of DNA polymerase during nucleotide incorporation into a DNA strand by
      analyzing the pyrophosphate released during the process. Today, the technique is
      used in multidisciplinary fields in academic, clinical, and industrial settings
      all over the word. The technique can be used for both single-base sequencing and
      whole-genome sequencing, depending on the format used. In this chapter I will
      give my personal account of the development of Pyrosequencing--beginning on a
      winter day in 1986, when I first envisioned the method--until today, nearly 20 yr
      later. I will conclude with future prospects for the method.

PMID- 17185754
TI  - Pyrosequencing applications.
AB  - Genetics research has benefited tremendously from the release of the human genome
      sequence. Subsequent technology has been developed and adapted to accommodate the
      need for faster, easier throughput of genetic assays. Pyrosequencing is a unique
      system that allows the analysis of genetic variations including single-nucleotide
      polymorphisms, indels and short repeats, as well as assessing RNA allelic
      imbalance, DNA methylation status, and gene copy number. Advances in methodology,
      including multiplex and universal primer applications, have reduced assay cost
      and improved throughput. This chapter briefly reviews some of the many
      applications for Pyrosequencing technology.

PMID- 17185756
TI  - Pyrosequencing: a simple method for accurate genotyping.
AB  - Pharmacogenetic research benefits first-hand from the abundance of information
      provided by the completion of the Human Genome Project. With such a tremendous
      amount of data available comes an explosion of genotyping methods. Pyrosequencing
      is one of the most thorough yet simple methods to date used to analyze
      polymorphisms. It also has the ability to identify tri-allelic, indels, short
      repeat polymorphisms, along with determining allele percentages for methylation
      or pooled sample assessment. In addition, there is a standardized control
      sequence that provides internal quality control. This method has led to rapid and
      efficient single-nucleotide polymorphism evaluation including many clinically
      relevant polymorphisms. The technique and methodology of Pyrosequencing is
      explained in this chapter.

PMID- 17185755
TI  - Web-based primer design software for genome-scale genotyping by pyrosequencing.
AB  - Design of locus-specific primers for use during genetic analysis requires
      combining information from multiple sources and can be a time-consuming process
      when validating large numbers of assays. Data warehousing of genomic DNA
      sequences and genetic variations when coupled with software applications for
      optimizing the generation of locus-specific primers can increase the efficiency
      of assay development. Selection of oligonucleotide primers for PCR and
      Pyrosequencing (SOP3) software allows user-directed queries of warehoused data
      collected from the human and mouse genome sequencing projects. The software
      automates collection of DNA sequence flanking single-nucleotide polymorphisms
      (SNPs) as well as the incorporation of locus-associated functional information,
      such as whether the SNP occurs in an exon, intron, or untranslated region. SOP3
      software accepts three types of user-directed input consisting of gene locus
      symbols, SNP reference sequence numbers, or chromosomal physical location. For
      human polymorphisms, SOP3 incorporates haplotype, ethnicity, and SNP validation
      attributes. The output is a list of oligonucleotide primers recommended for
      Pyrosequencing-based typing of genetic variations. SOP3 is available at the
      Division of Immunogenetics computational server found at
      http://imgen.ccbb.pitt.edu.

PMID- 17185757
TI  - Universal primer applications for pyrosequencing.
AB  - Pyrosequencing is a high-throughput technique for single-nucleotide polymorphism
      (SNP) genotyping, DNA sequencing, and SNP allele frequency and DNA methylation
      assays. The Pyrosequencing assay involves initially purifying PCR-generated
      single-strand DNA labeled with biotin as a sequencing template. The disadvantage
      of the synthesis of a biotinylated sequence-specific primer to assay each DNA
      variant lies in costs and time consumption. To overcome this problem, methodology
      has been developed to generate biotinylated Pyrosequencing DNA templates using a
      universal biotinylated primer. Using this methodology, biotinylated DNA fragments
      can be generated without the use of sequence-specific biotinylated primers for
      each DNA variant.

PMID- 17185758
TI  - Allele quantification and DNA pooling methods.
AB  - Studies utilizing differences in single-nucleotide polymorphism allele
      frequencies between cases and controls have been widely used in genetic analyses
      to locate putative genes or chromosomal regions that may be associated with a
      disease. In these studies the assessment of allele frequencies can be expedited
      and the genotyping costs reduced by the use of DNA pools. There have been
      multiple studies that have reported the accuracy of Pyrosequencing for the
      assessment of allele frequencies in DNA pools. In addition, there are an
      increasing number of other types of studies that make use of allele
      quantification to evaluate a disease status or to make a clinical diagnosis. In
      this chapter, the making of DNA pools is described, as well as the use of
      Pyrosequencing to quantify alleles. The ease of use, short run, and analysis
      times make Pyrosequencing the preferred method.

PMID- 17185759
TI  - Multiplex pyrosequencing for DNA variation analysis.
AB  - Pyrosequencing technique has been widely used to perform both single-nucleotide
      polymorphism detection and quantitative DNA methylation analysis. Simplex
      Pyrosequencing is sufficient to interrogate more than one polymorphic site if
      these gene variants are within the reach of the sequencing reaction. For
      polymorphisms far apart from each other or located on different genes, multiple
      simplex analyses are required. To reduce the number of simplex reactions,
      multiplex Pyrosequencing becomes a useful alternative method. The multiplex
      reaction is performed in the presence of single or multiple templates with
      several sequencing primers. Factors such as primer selection for the PCR and
      Pyrosequencing reaction, generation of optimal nucleotide dispensation order, use
      of internal and external controls, preparation of instrumentation, and Pyrogram
      interpretation are essential to the success of the multiplexing. In this chapter,
      the mouse 45S rRNA gene is used to present two general multiplex Pyrosequencing
      protocols for determining DNA methylation and allele frequency in the spacer
      promoter region of this gene.

PMID- 17185760
TI  - Analysis of gene-specific DNA methylation patterns by pyrosequencing technology.
AB  - As the sequence of the human genome is now nearly finished, genome research turns
      to elucidate gene function and regulation. DNA methylation is of particular
      importance for gene regulation and is strongly implicated in the pathogenesis of
      various diseases. The real-time luminometric detection of pyrophosphate release
      upon nucleotide incorporation in the Pyrosequencing technology is ideally suited
      for the simultaneous analysis and quantification of the methylation degree of
      several CpG positions in close proximity. We developed and improved this analysis
      to obtain reproducible results for as many as 10 successive CpGs in a single
      sequencing reaction spanning up to 80 nt. Advantages of the Pyrosequencing
      technology are the ease of its implementation, the high quality and the
      quantitative nature of the results, and its ability to identify differentially
      methylated positions in close proximity, which may be used as DNA methylation
      markers.

PMID- 17185761
TI  - Detecting mutations that confer oxazolidinone resistance in gram-positive
      bacteria.
AB  - Resistance to oxazolidinone antibiotics, including linezolid, in Gram-positive
      bacteria is mediated by single-nucleotide polymorphisms (SNPs) in the 23S
      ribosomal RNA. A G2576U change (encoded by a G2576T mutation in the rRNA genes)
      is found in most resistant clinical isolates of enterococci and staphylococci; a
      variety of changes have been found in resistant mutants selected in vitro.
      Pyrosequencing can be used to detect SNPs known to confer oxazolidinone
      resistance, including the G2576T change. Most bacteria have more than one rRNA
      gene copy and Pyrosequencing can also be used for allele quantification, i.e., to
      estimate the proportions of mutant vs wild-type alleles. The number of mutated
      rRNA gene copies correlates roughly with the level of oxazolidinone resistance
      displayed by resistant isolates. This chapter summarizes the Pyrosequencing
      assays that have been developed in our laboratory for analyzing oxazolidinone
      resistant enterococci and staphylococci.

PMID- 17185762
TI  - Pyrosequencing-based strategies for improved allele typing of human leukocyte
      antigen loci.
AB  - Successful transplantation of tissue during solid organ and bone marrow
      transplantation relies on accurate determination of the human leukocyte antigen
      (HLA) phenotype of the potential donor(s) and recipient. Matching donor with
      recipient for a kidney transplant generally means finding a six-antigen match by
      looking at each of two alleles at HLA-A, -B, and -DR loci. For bone marrow
      transplantation the HLA-C and -DQ alleles are also considered. Molecular
      techniques, including sequencing, are capable of precisely defining HLA alleles.
      Because of the large number of possible allelic combinations there are numerous
      ambiguities associated with heterozygous genotypes even when sequence-based
      typing protocols are used. Sequencing-by-synthesis methodology employed by
      Pyrosequencing represents an improvement when applied to HLA genotyping that
      allows resolution of many ambiguous allelic pairs. Out-of-phase sequencing of HLA
      alleles by Pyrosequencing can resolve cis/trans ambiguities that would otherwise
      require the sequencing of isolated cloned DNAs. Single-nucleotide polymorphism
      typing of HLA for the presence of specific variants is also beneficial for
      monitoring HLA-encoded genetic risk to autoimmune diseases, such as celiac
      disease, rheumatoid arthritis, and type 1 diabetes mellitus.

PMID- 17185763
TI  - Pyrosequencing of phage display libraries for the identification of cell-specific
      targeting ligands.
AB  - High combinatorial phage display libraries have become an important tool in the
      search for ligand-receptor interactions. The advantage this approach offers is
      the ability to screen large repertoires of peptides, displayed on the coat
      proteins of bacteriophages, against a target at the same time. In addition, no
      prior knowledge is required of the target or the ligand. However, to characterize
      the peptides of interest a short length of the bacteriophage genome that encodes
      the peptide sequence requires DNA sequencing. The number of candidate
      bacteriophages can be large and so sequencing is expensive, time-consuming, and
      laborious. Therefore, a methodology using Pyrosequencing has been developed where
      96-phage displaying a seven amino acid peptide can be analyzed simultaneously
      within 45 min and at a fraction of the cost associated with traditional automated
      Sanger sequencing.

PMID- 17185764
TI  - Gene copy number detection in animal studies.
AB  - Sensitive methods for the quantification of DNA fragments can be used to study an
      individual's genetic constitution for duplicated regions of the genome or to
      determine the relative proportion of different DNA fragments in heterogeneous
      samples such as pooled DNA from different individuals or in samples in which a
      fraction of the chromosomes carry a mutation. Here, we describe how we are using
      Pyrosequencing for this purpose. In Subheading 3., we describe a sensitive method
      that can be used to quantify the relative proportion of X- and Y-carrying sperm
      after sperm sorting in cattle. We also discuss our method for determining the
      copy numbers at a duplicated locus. This method has been applied to study genetic
      variation at the KIT locus in pigs, which have a major effect on coat color
      variation in this species.

PMID- 17185766
TI  - Pyrosequencing genotype storage techniques.
AB  - Data storage and data coordination are important aspects of project design and
      execution. Pyrosequencing technology allows thousands of data-points to be
      collected per day. Consequently, a consistent and reliable method of data input
      and storage is vital. This chapter discusses the strengths and weaknesses of data
      storage systems.

PMID- 17185765
TI  - Detection of allelic imbalance in gene expression using pyrosequencing.
AB  - Single-nucleotide polymorphisms (SNPs) are common in the human genome, with more
      than 11 million SNPs having frequencies greater than 1%. The challenge is to
      identify the minority of functional SNPs from the large number of SNPs that are
      expected to be silent. Whereas coding variants are unusual, and functional
      (nonsynonymous) coding SNPs likely rare, regulatory SNPs appear to be common.
      Traditional methods to identify these SNPs in vitro are time consuming and
      challenging. An alternative method is to examine the allele-specific expression
      in the cDNA from tissues expressing the genes of interest and in individuals
      heterozygous for a transcribed SNP. This method permits expression to be
      evaluated in the context of the same trans-acting factors and to identify genes
      with likely cis-acting regulatory variants or parent of origin (imprinting)
      effects. Such studies require a method to reliably quantify the expression from
      each allele. Pyrosequencing offers such capabilities, and given the relatively
      low cost and high throughput, it offers a sensitive method to determine allelic
      imbalance in the cDNA from tissues expressing genes of interest.

PMID- 17185767
TI  - Introduction to proteomics.
AB  - Mass spectrometry (MS) has recently become one of the most informative methods
      for studying proteins. Albiet, MS cannot compete with the detailed structural
      information obtained by methods such as nuclear magnetic resonance and X-ray
      crystallography. However, MS is much easier to automate and use as a large-scale
      technique. Large-scale proteomic methods are valuable for studying the dynamics
      of the proteins and their posttranslational modification in living cells. Despite
      the great potential of mass spectrometers, many laboratories are struggling with
      data analysis and data storage. The complexity of the data analysis stems from
      the large number of experiments that can be performed by various mass
      spectrometers. In addition, many mass spectrometers have their own data formats.
      Performing data analysis on MS data, therefore, requires a rather extensive setup
      of algorithms and data parsers. In recent years it has become evident that the
      proteomics society needs standard formats for storing and exchanging data. This
      has triggered a new problem, which is the invention of several different standard
      formats. In this chapter, an overview of the most common proteomics experiments
      with MS, together with an overview of data formats, is presented.

PMID- 17185768
TI  - Extracting monoisotopic single-charge peaks from liquid chromatography
      electrospray ionization-mass spectrometry.
AB  - Peak extraction from raw data is the first step in analysis of mass spectrometry
      (MS) data. The quality of this procedure is very important because it affects the
      quality of all subsequent analysis, such as database searches and peak
      quantitation. Many methods have been proposed in the literature, yet the number
      of practical solutions in terms of available software is rather limited. Virtual
      Expert Mass Spectrometrist (VEMS) v3.0 includes an algorithm for extracting
      monoisotopic single-charged peaks and their corresponding retention time from
      liquid chromatography (LC)-MS data. The extracted peaks can subsequently be
      exported to other programs or used internally by VEMS to perform peptide mass
      fingerprinting searches or peptide quantitation. Additionally, VEMS interfaces
      the commercial program ProteinLynx Global server v2.0.5 for automatic peak
      extraction from MS/MS spectra obtained by LC-MS/MS.

PMID- 17185769
TI  - Calibration of matrix-assisted laser desorption/ionization time-of-flight peptide
      mass fingerprinting spectra.
AB  - This chapter describes a number of aspects important for calibration of matrix
      assisted laser desorption/ionization time-of-flight spectra prior to peptide mass
      fingerprinting searches. Both multipoint internal calibration and mass defect
      based calibration is illustrated. The chapter describes how potential internal
      calibrants, like tryptic autodigest peptides and keratin-related peptides, can be
      identified and used for high-precision calibration. Furthermore, the construction
      of project/user-specific lists of potential calibrants is illustrated.

PMID- 17185770
TI  - Protein identification by peptide mass fingerprinting.
AB  - Peptide mass fingerprinting is an effective way of identifying, e.g., gel
      separated proteins, by matching experimentally obtained peptide mass data against
      large databases. However, several factors are known to influence the quality of
      the resulting matches, such as proteins contaminating the sample in question,
      modifications altering the mass of the peptides, ionization efficiency of the
      individual peptides, and the degree of missed cleavage sites. Here, these factors
      are discussed and methods for elimination of contaminants from the dataset and
      prediction of various modifications are introduced. Useful tips on how to specify
      various search parameters and how to manually evaluate the search results are
      also given.

PMID- 17185771
TI  - Generating unigene collections of expressed sequence tag sequences for use in
      mass spectrometry identification.
AB  - Expressed sequence tag sequences remain the largest resource of DNA sequence for
      most organisms despite recent advances in genome sequencing. These sequences are
      short, fragmented versions of the expressed genes. By DNA sequence assembly, the
      fragments can be assembled into contiguous DNA sequences that are better suited
      for protein identification by mass spectrometry.

PMID- 17185772
TI  - Protein identification by tandem mass spectrometry and sequence database
      searching.
AB  - The shotgun proteomics strategy, based on digesting proteins into peptides and
      sequencing them using tandem mass spectrometry (MS/MS), has become widely
      adopted. The identification of peptides from acquired MS/MS spectra is most often
      performed using the database search approach. We provide a detailed description
      of the peptide identification process and review the most commonly used database
      search programs. The appropriate choice of the search parameters and the sequence
      database are important for successful application of this method, and we provide
      general guidelines for carrying out efficient analysis of MS/MS data. We also
      discuss various reasons why database search tools fail to assign the correct
      sequence to many MS/MS spectra, and draw attention to the problem of false
      positive identifications that can significantly diminish the value of published
      data. To assist in the evaluation of peptide assignments to MS/MS spectra, we
      review the scoring schemes implemented in most frequently used database search
      tools. We also describe statistical approaches and computational tools for
      validating peptide assignments to MS/MS spectra, including the concept of
      expectation values, reversed database searching, and the empirical Bayesian
      analysis of PeptideProphet. Finally, the process of inferring the identities of
      the sample proteins given the list of peptide identifications is outlined, and
      the limitations of shotgun proteomics with regard to discrimination between
      protein isoforms are discussed.

PMID- 17185773
TI  - Virtual Expert Mass Spectrometrist v3.0: an integrated tool for proteome
      analysis.
AB  - The number of tools described in the literature for analysis of proteome data is
      growing fast. However, most tools are not able to communicate or exchange data
      with other tools. In Virtual Expert Mass Spectrometrist (VEMS) v3.0 an effort has
      been made to interface and export to already existing tools. In this chapter, an
      outline of how to use the VEMS program to search tandem mass spectrometry data
      against databases is described. Additionally, examples on how to extend the
      analysis with other external tools are given.

PMID- 17185774
TI  - Quantitation with virtual expert mass spectrometrist.
AB  - Quantitative analysis of proteins and peptides by mass spectrometry has been
      greatly advanced by the development of proteomic technologies within recent
      years. Particularly, labeling of peptides and proteins with stable isotopes such
      as 2H, 15N, and 13C facilitated the unbiased comparison of protein amounts in
      distinct samples in a single mass spectrometric experiment. These methods can be
      applied to detect quantitative changes in protein amounts and posttranslational
      modifications such as phosphorylation. Quantitation of mass spectra requires
      accurate and efficient bioinformatics tools, which can match corresponding
      peptides, determine peak intensities, and calculate relative amounts. In this
      chapter, we describe the use of virtual expert mass spectrometrist for the
      quantitation of mass spectra from samples with peptides and proteins encoded with
      stable isotopes.

PMID- 17185775
TI  - Sequence handling by sequence analysis toolbox v1.0.
AB  - The fact that mass spectrometry have become a high-throughput method calls for
      bioinformatic tools for automated sequence handling and prediction. For efficient
      use of bioinformatic tools, it is important that these tools are integrated or
      interfaced with each other. The purpose of sequence analysis toolbox v1.0 was to
      have a general purpose sequence analyzing tool that can import sequences obtained
      by high-throughput sequencing methods. The program includes algorithms for
      calculation or prediction of isoelectric point, hydropathicity index,
      transmembrane segments, and glycosylphosphatidyl inositol-anchored proteins.

PMID- 17185776
TI  - Interpretation of collision-induced fragmentation tandem mass spectra of
      posttranslationally modified peptides.
AB  - Tandem collision-induced dissociation (CID) mass spectrometry (MS) provides a
      sensitive means of analyzing the amino acid sequence of peptides. Modern MS
      instrumentation is capable of rapidly generating many thousands of tandem mass
      spectra, and protein database search engines have been developed to cope with
      this avalanche of data. In most studies, there is a schism between discarding
      perfectly valid data and including nonsensical peptide identifications--this is
      currently a major bottleneck in data analysis and it calls for manual evaluation
      of the data. Especially for posttranslationally modified peptides, there is a
      need for manual validation of the data because search algorithms seldom have been
      optimized for the identification of modified peptides and because there are many
      pitfalls for the unwary. This chapter describes some of the issues that should be
      considered when interpreting and validating low-energy CID tandem mass spectra
      and gives some useful tables to aid this process.

PMID- 17185777
TI  - Retention time prediction and protein identification.
AB  - Proteins are commonly identified through enzymatic digestion and generation of
      short sequence tags or fingerprints of peptide masses by mass spectrometry.
      Separation methods, such as liquid chromatography and electrophoresis, are often
      used to fractionate complex protein or peptide mixtures and these separations
      also provide information on the different species, such as molecular weight and
      isoelectric point from electrophoresis and hydrophobicity in reversed-phase
      chromatography. These are also properties that can be predicted from amino acid
      sequences derived from genomic sequences and used in protein identification. This
      chapter reviews recently introduced methods based on retention time prediction to
      extract information from chromatographic separations and the applications to
      protein identification in organisms with small and large genomes. Novel data on
      retention time prediction of posttranslationally modified peptides is also
      presented.

PMID- 17185778
TI  - Quantitative proteomics by stable isotope labeling and mass spectrometry.
AB  - The goal of quantitative proteomics is to systematically study static state or
      perturbation-induced changes in protein profile. Most of the recently developed
      mass spectrometry (MS)-based quantitative proteomic methods employ stable isotope
      labeling to introduce signature mass tags to peptides/proteins that can be used
      by a mass spectrometer to quantify each analyte and to determine the sample from
      which it originates. In this chapter, we discuss several methods for the
      introduction of mass tags to proteins and peptides for MS-based quantitative
      proteomic analysis, including isotope-coded affinity tags, stable isotope
      labeling by amino acids in cell culture, global internal standard technology, and
      mass-coded abundance tagging.

PMID- 17185779
TI  - Quantitative proteomics for two-dimensional gels using difference gel
      electrophoresis.
AB  - Difference gel electrophoresis (DIGE) technology provides a powerful quantitative
      component to proteomics experiments involving two-dimensional (2D) gel
      electrophoresis. DIGE allows for the detection of subtle changes in protein
      abundance with statistical confidence while controlling for gel-to-gel variation,
      as well as additional variation that is non-biological in origin (e.g., sample
      preparation error, normal variation in a system). Samples are differentially
      labeled with spectrally resolvable fluorescent dyes (Cy2, Cy3, and Cy5) and co
      resolved for direct quantification within the same 2D gel. Increased statistical
      confidence is obtained when combining experimental repetition with internal
      standards such that independent replicate measurements from single- and
      multivariable analyses can be intercompared with a relatively small number of
      coordinated DIGE gels.

PMID- 17185780
TI  - Proteomic data exchange and storage: using Proteios.
AB  - Proteios (http://www.proteios.org) is an initiative for the development of a
      comprehensive open source system for storage, organization, analysis, and
      annotation of proteomics experiments. The Proteios platform is based on existing
      principles for proteomics data publishing and data exchange.

PMID- 17185781
TI  - Proteomic data exchange and storage: the need for common standards and public
      repositories.
AB  - The ever increasing volumes of proteomic data now being produced by laboratories
      across the world have resulted in major issues in data storage and accessibility.
      The further demands of multilaboratory initiatives has highlighted issues when
      collaborators cannot import data generated within the same project but generated
      by different hardware types and processed by laboratory-specific work flows and
      analyses packages. There is an increasing need for common data standards that
      will allow the interchange of data between different instrumentation, search
      engines, and between laboratory databases. This could then lead to the
      establishment of data repositories from where benchmark datasets could be
      accessed and reanalyzed. The Human Proteome Organization is currently supporting
      efforts to establish such standards. The work of the Proteomics Standards
      Initiative has lead to the development of the mzData XML interchange standard and
      is now broadening its scope to produce a spectral analysis output format,
      mzIdent. Accompanying controlled vocabularies allow the accurate, while
      systematic, representation of metadata throughout both schema.

PMID- 17185782
TI  - Organization of proteomics data with YassDB.
AB  - In recent years the organization of mass spectrometry (MS) data obtained in large
      scale proteomics projects became an important issue. This has catalyzed the
      development of a few different database schemes for storing MS data, as well as
      some dedicated user interfaces. However, many of these projects are still rather
      immature and often do not cover all needs. Because our needs were quite specific,
      it was necessary to build a database that accommodates all the major types of
      experiments generated in house and that could be easily extended by new modules
      made by collaborators or students. A database application named "YassDB" will be
      described in this chapter. The application is implemented in a "three-tier"
      application architecture, with a database layer, a middle layer consisting of web
      services and a client layer, containing the user interface. This offers high
      flexibility: it allows other applications, written in any language, to be written
      as clients to the database. The setup and use of the YassDB database application
      with two client programs "pProRep" and "VEMS" will be outlined.

PMID- 17185783
TI  - Analysis of carbohydrates by mass spectrometry.
AB  - The analysis method described in this chapter demonstrates the structural
      characterization of carbohydrates based on their molecular mass, as well as the
      mass of their respective fragment ions using mass spectrometry (MS). The
      carbohydrate molecules are first converted into gaseous ions, under vacuum, after
      which their mass-to-charge ratio is measured. The mass-to-charge ratio provides
      information on their preliminary identification, which is further elucidated by
      fragmenting the ions under a process of collision-induced dissociation. The
      masses obtained in the first stage of MS together with those obtained in the
      subsequent stages (MSn) are combined into a mass list that is loaded into the
      program, Virtual Expert Mass Spectrometrist (VEMS) v3.0. The mass lists obtained
      are then used by VEMS to search a database of glycans to give the identity of the
      carbohydrate and the correct assignment of the fragment ions.

PMID- 17185784
TI  - Useful mass spectrometry programs freely available on the internet.
AB  - The intention with this chapter is to give an overview of a broad range of freely
      available programs on the internet which are useful for analyses of mass
      spectrometry data. The list is by no means a full list of free proteomics tools
      on the net and I apologize if there are other good tools on the internet that
      have been missed. The presented programs should cover the needs for the most
      general tasks in data analysis of proteomics data and have to a limited extend
      been tested. The links provided in this chapter will over time become invalid. In
      such cases it is worth while to try a World Wide Web search using the program
      packages names. This will often reveal the updated links. Some of the links
      presented in this chapter will also be maintained at http://yass.sdu.dk.

PMID- 17185785
TI  - Polycystic ovarian syndrome: insights into the enigma that is PCOS today.

PMID- 17185786
TI  - Diagnostic criteria for polycystic ovarian syndrome.
AB  - Until recently no universally accepted clinical definition existed for the
      polycystic ovary syndrome (PCOS). What has emerged from research over the last 30
      yr is a profound heterogeneity and ongoing speculation regarding etiology. The
      various symptoms and signs related to PCOS have now been extensively evaluated as
      to their possible contribution to the diagnosis. Consensus has been reached for
      the use of oligomenorrhea or amenorrhea, clinical or biochemical
      hyperandrogenism, and polycystic ovaries at ultrasound as key diagnostic
      criteria. Obesity, insulin resistance, and the so-called metabolic syndrome
      should be recognized as associated conditions that present long-term health risks
      for diagnosed PCOS cases. The way all these features need to be applied in the
      work up of the individual index patient is reviewed here.

PMID- 17185787
TI  - Insulin resistance in PCOS.
AB  - Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy affecting women
      of reproductive age, manifested with a variety of clinical signs, none of which
      is pathognomonic. The association of insulin resistance and reproductive
      abnormalities with clinical hyperandrogenism in a woman was first demonstrated by
      Achard and Thiers in the "diabetes of bearded woman." The link of PCOS with
      insulin resistance was subsequently established by clinical studies
      characterizing the profound insulin resistance in obese and lean PCOS patients.
      Insulin resistance, hyperinsulinemia, and beta-cell dysfunction are very common
      in PCOS, but are not required for the diagnosis. The numerous in vivo and in
      vitro data supporting the central role of insulin resistance in the pathogenesis
      of PCOS found a broad clinical application in the management of the syndrome,
      where the regulation of cycle abnormalities and the facilitation of pregnancy in
      obese PCOS patients was assisted by co-administration of agents such as the well
      known insulin sensitizers. The documentation of the presence of insulin
      resistance contributed substantially to unravel several metabolic components
      present in the syndrome. Today our knowledge about PCOS appears to have broader
      health implications and to have profoundly altered our view of the gravity of
      this condition.

PMID- 17185788
TI  - The role of genes and environment in the etiology of PCOS.
AB  - Both genes and the environment contribute to PCOS. Obesity, exacerbated by poor
      dietary choices and physical inactivity, worsens PCOS in susceptible individuals.
      The role of other environmental modifiers such as infectious agents or toxins are
      speculative. Phenotype confusion has characterized genetic studies of PCOS.
      Although several loci have been proposed as PCOS genes including CYP11A, the
      insulin gene, the follistatin gene, and a region near the insulin receptor, the
      evidence supporting linkage is not overwhelming. The strongest case can be made
      for the region near the insulin receptor gene (but not involving this gene), as
      it has been identified in two separate studies, and perhaps most importantly has
      not yet been refuted by larger studies. However, the responsible gene at
      chromosome 19p13.3 remains to be identified. To date, no gene has been identified
      that causes or contributes substantially to the development of a PCOS phenotype.

PMID- 17185789
TI  - Infertility in polycystic ovary syndrome: focus on low-dose gonadotropin
      treatment.
AB  - Polycystic ovary syndrome accounts for more than 75% of cases of anovulatory
      infertility. The mechanism of anovulation is uncertain but there is evidence that
      arrested antral follicle development is associated with the abnormal endocrine
      profile, in particular the interaction of insulin and LH on granulosa cell
      differentiation. In terms of management, induction of ovulation can be achieved
      in most cases by the use of antiestrogens. Treatment of clomiphene-resistant
      subjects is difficult; conventional doses of gonadotropins are associated with
      high rates of ovarian hyperstimulation syndrome and multiple pregnancy. On the
      other hand, low-dose gonadotropin therapy has proven effective in inducing
      unifollicular ovulation and, in this review, we present, in detail, a recent
      analysis the results from this center. The cumulative conception rate after six
      cycles was more than 50% and, importantly, the multiple pregnancy rate was only
      3%. Weight reduction in obese subjects with PCOS not only increases the chance of
      fertility but may also improve the long-term prognosis with regard to development
      of diabetes. Insulin-sensitizing drugs such as metformin may also have a place in
      treatment of PCOS.

PMID- 17185790
TI  - Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is significantly affected by environmental
      regulators impacting on genetic predisposition. Lifestyle changes can
      significantly modulate the phenotype of this disease. Diet, exercise, smoking,
      stress, and other factors adversely affect reproductive outcomes in PCOS. These
      influences can be modulated by structure change in an individual or group.
      Lifestyle choices should be discussed in this group of patients. The role of
      insulin sensitizers, including metformin, has still to be determined in this
      condition.

PMID- 17185792
TI  - Differential regulation of GHRH-receptor and GHS-receptor expression by long-term
      in vitro treatment of ovine pituitary cells with GHRP-2 and GHRH.
AB  - GH secretion is regulated by GHRH and somatostatin via actions on their specific
      receptors in pituitary somatotropes. Ghrelin and synthetic analogs, GHRPs, also
      stimulate GH release via GHS-receptors (GHS-R). To examine the long-term effect
      of GHRH and/or GHRP on somatotropes, primary cultured ovine somatotropes were
      treated with GHRH (10(-9) and 10(-8) M) and GHRP-2 (10(-8) and 10(-7) M) for up
      to 2 d. After treatment, culture medium was collected for GH assay, and total RNA
      was extracted for RT-PCR analysis. To evaluate cell cultures used in this report,
      somatotrope-enriched pituitary cells were challenged by 6 h GHRH and
      dexamethasone (DEX) treatment. As expected, GHRH significantly decreased, whereas
      DEX increased, the levels of GHRHR mRNA. Combined low doses of GHRH (10(-9) M)
      and GHRP-2 (10(-8) M) treatment for 24 h increased accumulated GH secretion,
      significantly more than that induced by high doses of GHRH (10(-8) M) and GHRP-2
      (10(-7) M). While levels of GHRH-R mRNA increased, GHS-R mRNA levels were
      decreased by low doses of GHRH and GHRP-2 for 24 h. High doses of GHRH and/or
      GHRP-2 for 2 d did not increase GH secretion in the second day of treatment and
      reduced the level of GHRH-R mRNA. High doses of GHRP-2 treatment decreased the
      levels of both GHRH-R and GHS-R mRNA. Low doses of GHRH and/or GHRP-2 for 2 d
      increased the level of GHS-R mRNA without changing GHRH-R mRNA levels. Such
      treatment also increased ghrelin- (10(-9) M) or ghrelin/GHRH (10(-9) M)-induced
      GH secretion. These results suggest that low doses of GHRP-2 and GHRH prime
      somatotropes for stimulation by GHRH and ghrelin.

PMID- 17185791
TI  - Insulin resistance, the metabolic syndrome, diabetes, and cardiovascular disease
      risk in women with PCOS.
AB  - Polycystic ovary syndrome is the most common endocrinopathy of reproductive aged
      women affecting 6-10% of the population. Traditionally considered a reproductive
      disorder manifesting as chronic anovulation, infertility, and hyperandrogenism,
      management has primarily focused on short-term reproductive outcomes. Recently,
      however, significant metabolic aspects in conjunction with longer-term health
      sequealae of PCOS have been recognized. The metabolic features are primarily
      related to underlying insulin resistance (IR), which is now understood to play an
      important role in both the pathogenesis and long-term sequelae of PCOS.

PMID- 17185793
TI  - Investigation of tissue factor and other hemostatic profiles in experimental
      hypothyroidism.
AB  - The influence of thyroid failure on hemostasis has been studied and is still not
      well understood. These patients have high risk for cardiovascular diseases
      because of the lipid metabolism and procoagulant agents. But the influence of
      thyroid failure on hemostasis is controversial. Tissue factor (TF) has an
      important role in the thromboembolic state. Recent experiments have demonstrated
      that TF-dependent activation of the coagulation cascade plays an important role
      in the pathophysiology of intravascular thrombus formation. The purpose of the
      present study was to investigate the contributions of TF, factor VII:C (FVII:C),
      factor XII:C (FXII:C), and fibrinogen in experimental hypothyroidism. TF was
      obtained from the thyroid gland and lung tissue of 10 rats following experimental
      hypothyroidism induced for 30 d and compared with similar tissue from 10 control
      rats. Significantly increased TF activities were found in hypothyroid rats. By
      contrast, FVII:C level was significantly decreased when compared with the control
      group. In this respect it is interesting to note that a hypercoagulable state due
      to increased thromboplastic activity may occur. Based on those results, elevated
      tissue factor activities (TFa) of the patients with low thyroid dysfunction may
      have another risk factor for cardiovascular diseases.

PMID- 17185794
TI  - Effects of high-fat diets on body composition, hypothalamus NPY, and plasma
      leptin and corticosterone levels in rats.
AB  - We investigated the adipogenic effects of high-fat diets with different fat
      sources, as well as their influence on hypothalamus NPY content (NPY) and plasma
      corticosterone (Cs) and leptin (Lep) concentrations. In a 6-wk experiment
      performed in 28 male Wistar rats, high-fat diets (approx 60% of energy as fat)
      containing sunflower oil (S), rapeseed oil (R), palm oil (P), or lard (L) as the
      fat source were applied. Carcass composition was analyzed by standard methods;
      NPY, Cs, and Lep were determined by RIA method. Gas chromatography was applied to
      measure fatty acid composition of dietary fats. S group had the highest body fat
      content and Lep and the lowest Cs and NPY, while L rats had high Lep and the
      highest Cs and NPY. We conclude that the fatty acid composition of dietary fat is
      of high importance where effects of high fat diets on adiposity, as well as on
      plasma levels of both hormones and hypothalamus NPY content are concerned.

PMID- 17185795
TI  - Centrally administered neuropeptide S activates orexin-containing neurons in the
      hypothalamus and stimulates feeding in rats.
AB  - Neuropeptide S (NPS) is a newly identified transmitter that modulates arousal and
      anxiety. To determine potential neuronal targets for NPS, we studied the pattern
      of neuronal activation as indicated by the expression of Fos. Centrally
      administered NPS increased Fos-like immunoreactivity (FLI) in the
      paraventricular, dorsomedial nuclei and lateral hypothalamic area (LHA) of the
      hypothalamus, the midline thalamic nuclei, and the amygdala, many parts of which
      are involved in the regulation of emotion, arousal, and feeding. In particular,
      we noted that Fos-immunoreactive (Fos-ir) levels were increased in orexin
      expressing neurons in the LHA. We then studied whether an icv injection of NPS
      increased food intake. The injection of NPS (1 nmol) significantly stimulated
      feeding at 2 h in rats, but there was no difference in food intake at 4 h or 24
      h. These results suggest that arousal and feeding induced by NPS in the central
      nervous system may be related to the activation of orexin-expressing neurons.

PMID- 17185796
TI  - The murine p8 gene promoter is activated by activating transcription factor 4
      (ATF4) in the gonadotrope-derived LbetaT2 cell line.
AB  - The factor p8 is a high mobility group (HMG) A family member that is upregulated
      during the cellular stress response in numerous tissues. Because expression of
      this protein encourages cellular transformation, our goal is to characterize the
      mechanism by which the p8 gene is regulated. Using LbetaT2 cells as a model of a
      transformed cell in which p8 plays a role in tumor formation, we dissected the p8
      promoter into its minimal functional units and found that activating
      transcription factor 4 (ATF4), a factor also upregulated during cellular stress
      responses, enhances p8 promoter activity in a dose-dependent manner. In addition,
      ATF4 binds in the highly conserved major activation domain of the p8 proximal
      promoter between -130 and -100 bp. Furthermore, we show that six of the nine base
      pairs that encompass the putative element are essential for ATF4 binding. These
      findings increase our knowledge of the mechanisms regulating the p8 gene in a
      genetically defined tumor model.

PMID- 17185797
TI  - Effects of Pueraria mirifica, an herb containing phytoestrogens, on reproductive
      organs and fertility of adult male mice.
AB  - The effects of Pueraria mirifica (PM) on reproductive organs and fertility of
      adult male mice were investigated. Male mice were divided into four groups (10
      mice/group). Groups 1-3 were orally treated with PM at doses of 0 (PM-0), 10 (PM
      10), and 100 (PM-100) mg/kg BW/d in 0.2 mL distilled water, and group 4 was
      subcutaneously injected with 200 microg/kg BW/d of synthetic estrogen
      diesthylstilbestol (DES). The treatment schedule was separated into two periods:
      treatment and posttreatment (8 wk for each period). The PM-10 and PM-100
      treatments had no effect on testicular weight, sperm number, and serum LH, FSH,
      and testosterone levels. Only the PM-100 treatment reduced weights of epididymes
      and seminal vesicle and the sperm motility and viability. Histopathological
      examination demonstrated that testis, epididymis, and seminal vesicle were normal
      in all doses of PM treatment. PM-treated males showed no alterations in mating
      efficiency and on causing pregnancy of their female partners. DES injection
      impaired all those parameters. Offspring fathered by the PM- and DES-treated
      males exhibited neither malformations nor change of body weight gains, and the
      reproductive organ weights of 50-d old pups were in the normal range. The present
      data clearly demonstrate that a long-term treatment of PM at doses 10 and 100
      mg/kg BW/d, via oral route, does not alter a male fertility and a hypothalamus-
      pituitary-testis axis. Although PM-100 can cause some moderate impairment, no
      persistent effects were observed. Most of PM-treated mice increased the mating
      efficiency after stop treatment.

PMID- 17185798
TI  - PYY in the expanding pancreatic epithelium.
AB  - Gut peptide YY (PYY) plays an important role in regulating metabolism and is
      expressed during the ontogeny of the pancreas. However, its biological role
      during endocrine cell formation is not fully understood, and its role, if any,
      during pancreatic regeneration in the adult has not yet been explored. The
      knowledge of factors involved in beta cell renewal in adult animals is clearly
      relevant for the design of treatment strategies for type 1 diabetes. We therefore
      sought to determine if observations during fetal pancreas formation also apply to
      pancreatic growth in adult animals. Indeed, we have found marked expansion of the
      PYY-expressing population during pancreatic regeneration. In addition, we
      demonstrate the presence of cells co-expressing PYY and the critical pancreatic
      transcription factor pancreatic duodenal homeobox1 (PDX-1). Interestingly, these
      cells also co-expressed specific islet hormones during pancreatic development and
      re-growth, suggesting a developmental relationship. Furthermore, we have found
      that PYY can act in concert with IGF-1 to stimulate cellular responsiveness in
      pancreatic epithelial cells in vitro. Our data suggest that PYY may be a mediator
      of islet cell development, as well as a cofactor for growth factor responses, not
      only during fetal pancreas formation but also during regeneration in adult
      animals.

PMID- 17185800
TI  - Endothelin-1 receptor blockade prevented the electrophysiological dysfunction in
      cardiac myocytes of streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus is complicated with the development of cardiac contractile
      dysfunction and electrical instability, which contributes to high morbidity and
      mortality in diabetic patients. This study examined the possible roles of
      enhanced endothelin-1 (ET-1) on diabetes-induced alterations in ventricular
      myocyte electrophysiology. Type 1 diabetic rats were induced by single dose
      injection of streptozotocin (STZ) and treated with or without ET-1 receptor
      antagonist bosentan for 8 wk before myocyte isolation. Action potential, outward
      K+ currents, and inward Ca2+ currents in ventricular myocytes were recorded using
      whole-cell patch clamp technique. STZ-injected rats exhibited hyperglycemia,
      reduced body weight gain, and elevated plasma ET-1 concentration, indicative of
      diabetes induction. Ventricular myocytes isolated from diabetic rats exhibited
      prolonged action potential and reduced all three types of outward K+ currents.
      Resting membrane potential, height of action potential, and L-type Ca2+ current
      were not altered in diabetic myocytes. In vivo chronic treatment of diabetic rats
      with bosentan significantly augmented K+ currents and reversed action potential
      prolongation in ventricular myocytes. On the other hand, bosentan treatment had
      no detectable effect on the electrophysiological properties in control myocytes.
      In addition, bosentan had no effect on Ltype Ca2+ currents in both control and
      diabetic myocytes. Our data suggest that altered electrophysiological properties
      in ventricular myocytes were largely resulted from augmented ET-1 system in
      diabetic animals.

PMID- 17185799
TI  - Topical ER36009, a RARgamma-selective retinoid, decreases abdominal white adipose
      tissue and elicits changes in expression of genes related to adiposity and
      thermogenesis.
AB  - Chronic topical treatment of rats with a new RARgamma-selective retinoid,
      ER36009, resulted in a significant reduction of epididymal white adipose tissue
      and a significant increase of interscapular brown adipose tissue without
      affecting food intake. ER36009 markedly decreased PPARgamma, 11beta-HSD1, and Bcl
      2 mRNA levels, and increased Bax mRNA in white adipose tissue, while it
      upregulated UCP1 and UCP3 mRNAs in brown adipose tissue and UCP3 mRNA in
      gastrocnemial muscle. These results suggest that ER36009 has multiple effects on
      adipose tissue biology and the energy balance. Topically applied ER36009 may have
      potential for the treatment of obesity.

PMID- 17185801
TI  - Functional thyrotropin receptor attenuates malignant phenotype of follicular
      thyroid cancer cells.
AB  - Thyrotropin (TSH) is a thyroid-specific growth factor inducing differentiated
      function and growth of thyrocytes in vitro. In thyroid cancer, loss of TSH
      receptor (TSHR) expression is a sign of de-differentiation and is believed to
      contribute to the malignant phenotype. The present studies aimed to determine the
      in vitro and in vivo effects of functioning TSHR in the follicular thyroid cancer
      cell line HTC, a subclone of FTC133 cells, lacking endogenous expression of TSHR,
      and HTCtshr+ cells transfected with human TSHR-cDNA. HTCtshr+ cells grew faster
      in vitro (doubling time 1.15 vs 1.56 d, p < 0.05) and TSH caused a dose-dependent
      growth response. Adhesion to and invasion through reconstituted basement membrane
      were reduced in HTCtshr+ cells, but when stimulated with TSH increased to levels
      comparable to naive HTC cells. In vivo, tumor latency was 11 d for naive HTC as
      compared to 21 d for HTCtshr+ xenografts. Smaller tumor volumes were registered
      for HTCtshr+ cells (250 +/- 217 vs 869 +/- 427 mm3, p < 0.05). Angiogenesis, as
      determined by vascular surface density (VSD) of experimental tumors, was enhanced
      in naive HTC tumors (VSD 0.87 +/- 0.1 microm-1 vs 0.55 +/- 0.2 microm-1 in
      HTCtshr+, p < 0.05). VEGF secretion was more pronounced in naive HTC cells
      stimulated with EGF, than in HTCtshr+ cells stimulated with either TSH or EGF. In
      conclusion, regained expression of functional TSHR in the follicular thyroid
      cancer cell line HTC alters in vitro features commonly associated with the
      malignant phenotype. Smaller tumors and reduced angiogenesis of xenotransplanted
      HTC cells with functioning TSHR suggest a less aggressive in vivo phenotype. The
      present data highlight the pivotal role of TSHR to affect transformed thyrocytes
      in vitro and in vivo. They also suggest a role for EGF as a modulator of
      angiogenesis in thyrocytes devoid of TSHR.

PMID- 17185802
TI  - Regulation of GnRH I receptor gene expression by the GnRH agonist triptorelin,
      estradiol, and progesterone in the gonadotroph-derived cell line alphaT3-1.
AB  - The secretion of luteinizing hormone (LH) and the GnRH receptor (GnRH-R)
      concentration are modulated by ovarian steroids and GnRH. To elucidate whether
      this regulation is due to alterations at the transcriptional level, we examined
      the GnRH I-R mRNA expression in the gonadotroph-derived cell line alphaT3-1
      treated with different estradiol and progesterone paradigms and the GnRH I
      agonist triptorelin. alphaT3-1 cells were treated with different steroid
      paradigms: 1 nM estradiol or 100 nM progesterone for 48 h alone or in
      combination. Cells were exposed to 10 nM or 100 pM triptorelin for 30 min, 3 h, 9
      h, or, in pulsatile way, with a 5-min pulse per hour. The GnRH I-R mRNA was
      determined by Northern blot analysis. GnRH I-R mRNA from cells treated with
      continuous triptorelin decreased in a time- and concentration-dependent manner.
      Pulsatile triptorelin increased GnRH I-R gene expression. Progesterone alone
      further enhanced this effect, whereas estradiol and its combination with
      progesterone diminished it. Continuous combined treatment with estradiol and
      progesterone lead to a significant decrease of GnRH I-R mRNA by 30% and by 35%
      for estradiol alone. The addition of 10 nM triptorelin for 30 min or 3 h could
      not influence that steroid effect. In conclusion, estradiol and progesterone
      exclusively decreased GnRH I-R mRNA in alphaT3-1 cells no matter whether they are
      treated additionally with the GnRH I agonist triptorelin. The enhanced
      sensitivity of gonadotrophs and GnRH I-R upregulation by estradiol is not due to
      increased GnRH I gene expression because GnRH I-R mRNA is downregulated by
      estradiol and progesterone. Other pathways of the GnRH I-R signal transduction
      might be involved.

PMID- 17185806
TI  - What do we know about fracture risk in long-duration spaceflight?

PMID- 17185805
TI  - What do we know about alteration in the osteoblast phenotype with microgravity?

PMID- 17185803
TI  - Acromegaly presenting with diabetic ketoacidosis, associated with retinitis
      pigmentosa and octreotide-induced bradycardia: a case report and a review of the
      literature.
AB  - Carbohydrate intolerance is a common feature of acromegaly. Frank diabetes
      mellitus is seen in about 10-20% of patients. There is no report of acromegaly
      presenting with diabetic ketoacidosis (DKA), associated with retinitis pigmentosa
      (RP), in the literature. We report the occurrence of DKA and RP in a patient with
      acromegaly. A 39-year-old Turkish man was admitted to the emergency ward with a 1
      mo history of thirst, polyuria, weight loss of 10 kg, and loss of consciousness
      for 2 d. Physical examination revealed findings suggestive of acromegaly,
      including coarse facial features and enlargement of his hands and feet. At
      ophthalmological examination, funduscopy showed RP. Laboratory studies confirmed
      the diagnoses of DKA and acromegaly. Magnetic resonance imaging disclosed the
      presence of a pituitary adenoma. During the medical treatment with octreotide,
      symptomatic sinusoidal bradycardia was developed (pulse rate 45 bpm, and blood
      pressure 70/40 mmHg). Octreotide therapy was stopped. Pituitary adenoma was
      removed surgically. For treatment of DKA, insulin need was very high in the first
      days after the onset of ketoacidosis, but decreased after initiation of treatment
      with octreotide and after successful operation. Insulin was stopped 7 d after
      surgery. Follow-up showed normalization of growth hormone levels and plasma
      glucose levels. Only six other cases of DKA associated with acromegaly and only
      three other cases of RP associated with acromegaly were found in the medical
      literature. In conclusion, to our knowledge, the present case is a first report
      of DKA and RP in patient with acromegaly.

PMID- 17185807
TI  - Microgravity and drug effects on bone.

PMID- 17185808
TI  - Does altered blood flow to bone in microgravity impact on mechanotransduction?

PMID- 17185809
TI  - A simulated weightlessness state diminishes cortical bone healing responses.

PMID- 17185811
TI  - Osteocytes as multifunctional cells.

PMID- 17185812
TI  - Vitamin D--the iceberg nutrient.

PMID- 17185813
TI  - Molecular regulation of calcium and bone metabolism through the vitamin D
      receptor.

PMID- 17185814
TI  - Vitamin D: clinical measurement and use.

PMID- 17185815
TI  - Vitamin D analogs as anabolic agents.

PMID- 17185816
TI  - Vitamin D as a defensin.

PMID- 17185818
TI  - TGF-beta regulation of osteoblast differentiation and bone matrix properties.

PMID- 17185819
TI  - The dysfunctional muscle-bone unit in juvenile idiopathic arthritis.

PMID- 17185820
TI  - Non-invasive imaging of osteoclast activity via near-infrared cathepsin-K
      activatable optical probe.

PMID- 17185821
TI  - Mechanical stimulation in vivo reduces osteocyte expression of sclerostin.

PMID- 17185822
TI  - Human genetics of SOST.

PMID- 17185823
TI  - Wnt signaling is involved in the inhibitory action of sclerostin on BMP
      stimulated bone formation.

PMID- 17185824
TI  - Downregulation of SOST/sclerostin by PTH: a novel mechanism of hormonal control
      of bone formation mediated by osteocytes.

PMID- 17185826
TI  - Small leucine-rich proteoglycans in the aging skeleton.
AB  - Small Leucine-Rich Proteoglyans (SLRPs) are major skeletal extracellular matrix
      (ECM) components that comprise a family of 13 members containing repeats of a
      leucine-rich motif. To examine SLRP function, we generated mice deficient in one
      or more member and analyzed them at the tissue, cell and molecular levels. This
      review outlines the novel research findings uncovered using these new animal
      models.

PMID- 17185827
TI  - Fibrillin microfibrils: connective tissue pathways that regulate shape and
      signaling.

PMID- 17185828
TI  - Contextual regulation of bone development, remodeling and regeneration by
      thrombospondin matricellular proteins.

PMID- 17185829
TI  - Dynamics of bone extracellular matrix assembly and mineralization.

PMID- 17185830
TI  - The mineralized extracellular "matrix" reloaded: a tissue engineering
      perspective.

PMID- 17185832
TI  - Clinical aspects, pathology and pathophysiology of osteoarthritis.

PMID- 17185833
TI  - Cellular, molecular, and matrix changes in cartilage during aging and
      osteoarthritis.

PMID- 17185834
TI  - MR imaging and early cartilage degeneration and strategies for monitoring
      regeneration.

PMID- 17185835
TI  - Pain and OA.

PMID- 17185838
TI  - Calcium homeostasis: solving the solubility problem.
AB  - This report summarizes the evidence that the control of the concentration of free
      calcium ions in body fluids is centered at mineralized bone surfaces. This
      process involves an increase in the solubility of bone mineral produced by the
      non-collagenous proteins existing in the bone extracellular fluid (ECF) and on
      the adjacent surfaces of bone. The result is a basic equilibrium level produced
      in the absence of parathyroid hormone (PTH), which is well above the solubility
      of bone mineral. The effect of PTH is to increase the solubility of bone mineral
      still further, but the mechanism by which the hormone acts is unknown. The lining
      cells of the bone contain receptors for PTH and can be observed to respond to
      this hormone, but the relationship between this response and the increased
      solubility of bone remains to be discovered. Further research in this field is
      strongly urged.

PMID- 17185839
TI  - The influence of mechanical stimulation on osteocyte apoptosis and bone viability
      in human trabecular bone.
AB  - It has been shown previously using in vivo and ex vivo animal models, that
      cyclical mechanical stimulation is capable of maintaining osteocyte viability
      through the control of apoptotic cell death. Here we have studied the effect of
      mechanical stimulation on osteocyte viability in human trabecular bone maintained
      in a 3-D bioreactor system. Bone samples, maintained in the bioreactor system for
      periods of 3, 7 and 27 days, were subjected to either cyclical mechanical
      stimulation which engendered a maximum of 3,000 microstrain in a waveform
      corresponding to physiological jumping exercise for 5 minutes daily or control
      unloading. Unloading resulted in a decrease in osteocyte viability within 3 days
      that was accompanied by increased levels of cellular apoptosis. Mechanical
      stimulation significantly reduced apoptosis (p< or =0.032) and improved the
      maintenance of osteocyte viability in bone from all patient samples. The
      percentage Alkaline Phosphatase (ALP) labelled bone surface was significantly
      increased (p< or =0.05) in response to mechanical stimulation in all samples as
      was the Bone Formation Rate (BFR/BS) (p=0.005) as determined by calcein label
      incorporation in the 27-day experiment. These data indicate that in this model
      system, mechanical stimulation is capable of maintaining osteocyte viability in
      human bone.

PMID- 17185841
TI  - Specimen collection methods in the diagnosis of childhood tuberculosis.

PMID- 17185843
TI  - Total quality management in clinical virology laboratories.
AB  - The diagnostic laboratories in India are progressively promoting higher standards
      and are moving towards accreditation and international acceptance. Hence, the
      concept of "Quality" will need to be understood and implemented. Total quality
      management (TQM) in a laboratory is an integrated program involving all
      laboratory staff and management. TQM is a framework to operate and it is aiming
      for integration, consistency, increase in efficiency and a continuous drive for
      improvement. A well structured clinical virology service will include serology
      setup, cell culture facility and capacity for molecular diagnosis. The quality of
      results from the laboratory is significantly influenced by many pre-analytical
      and post-analytical factors which needed attention. The end goal of the TQM
      should be to provide the best care possible for the patient.

PMID- 17185842
TI  - Rotavirus vaccines.
AB  - Rotavirus, the most common cause of severe diarrhea and a leading cause of
      mortality in children, has been a priority target for vaccine development for the
      past several years. The first rotavirus vaccine licensed in the United States was
      withdrawn because of an association of the vaccine with intussusception. However,
      the need for a vaccine is greatest in the developing world, because the benefits
      of preventing deaths due to rotavirus disease are substantially greater than the
      risk of intussusception. Early vaccines were based on animal strains. More
      recently developed and licensed vaccines are either animal-human re-assortants or
      are based on human strains. In India, two candidate vaccines are in the
      development process, but have not yet reached efficacy trials. Many challenges
      regarding vaccine efficacy and safety remain. In addition to completing clinical
      evaluations of vaccines in development in settings with the highest disease
      burden and virus diversity, there is also a need to consider alternative vaccine
      development strategies.

PMID- 17185844
TI  - Candida colonization in preterm babies admitted to neonatal intensive care unit
      in the rural setting.
AB  - PURPOSE: Candida colonization in neonates results in significant morbidity and
      mortality. The purpose of this study was to determine colonization of Candida
      spp. in preterm babies and identify the risk factors. METHODS: Swabs from oral,
      rectum, groin and umblicus of 103 preterm and 100 term neonates were obtained
      within 24 hours of birth, day three, day five, day seven and thereafter every
      week till the neonate was admitted in the neonatal intensive care unit (NICU).
      Swabs were also collected from the mother's vagina prior to delivery. Twice every
      month, air of the NICU was sampled by settle plate and swabs were collected from
      the hands of health care workers and inanimate objects of NICU. Identification
      and speciation was done by standard methods. Antibiotic sensitivity was studied
      against amphotericin B, ketoconazole and fluconazole by disk diffusion method.
      RESULTS: Colonization with Candida was significantly higher in preterms. Earliest
      colonization was of oral mucosa and 77.1% of the preterms had colonised at
      various sites by the first week of life. Significant risk factors in colonized
      versus non-colonized preterms were male sex, longer duration of rupture of
      membranes (DROM), administration of steroids and antibiotics and vaginal
      colonization of mothers, whereas those in preterms versus terms were low birth
      weight and gestational age. C. albicans was the commonest species, both in the
      colonized preterms (45.9%) and vagina of mothers. Resistance was seen to
      fluconazole and ketoconazole only. No Candida spp. was isolated from health care
      personnel or environment. CONCLUSIONS: Colonization of preterms by Candida is a
      significant problem in NICU and the significant risk factors observed in
      colonized preterms were male sex, longer DROM, administration of steroids and
      antibiotics and vaginal colonization of mothers.

PMID- 17185845
TI  - Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis: its
      utility in resource poor settings.
AB  - PURPOSE: To compare the rapid colorimetric nitrate reductase based antibiotic
      susceptibility (CONRAS) test performed on Mycobacterium tuberculosis isolates
      with the conventional method i.e, the proportion method. METHODS: One hundred
      clinical isolates of M. tuberculosis were tested for susceptibility to isoniazid
      (INH) and rifampicin (RIF) by the conventional proportion method and CONRAS in
      Middlebrook 7H9 liquid medium enriched with growth supplements (MB7H9S). RESULTS:
      The performance of the CONRAS test was evaluated using proportion method as the
      gold standard. The sensitivity (ability to detect true drug resistance) and
      specificity (ability to detect true drug susceptibility) of the CONRAS test to
      INH was 93.75 and 98.52% and for RIF it was 96.10 and 100% respectively. The mean
      time for reporting was 6.3 days and the test showed excellent reproducibility.
      The kappa (k) value for INH was 0.92 and for RIF was 0.99, indicating excellent
      agreement between the two methods. CONCLUSIONS: CONRAS test is a rapid and
      reliable method of drug susceptibility for M. tuberculosis.

PMID- 17185846
TI  - In-vitro susceptibility testing by agar dilution method to determine the minimum
      inhibitory concentrations of amphotericin B, fluconazole and ketoconazole against
      ocular fungal isolates.
AB  - PURPOSE: To standardize in-vitro antifungal susceptibility testing by agar
      dilution method to find out the minimum inhibitory concentration (MIC) of
      amphotericin B, fluconazole and ketoconazole on ocular fungal isolates. METHODS:
      A total of 180 ocular fungal isolates (130 filamentous fungi and 50 yeasts) were
      included. The antifungal drugs such as amphotericin B (0.0625-8 microg/mL),
      fluconazole (0.2-819.6 microg/mL) and ketoconazole (0.025-6.4 microg/mL) were
      incorporated in doubling dilutions in the yeast nitrogen base medium. The MIC was
      determined as the lowest concentration of the antifungal drug preventing growth
      of macroscopically visible colonies on drug containing plates when there was
      visible growth on the drug-free control plates. RESULTS: All 50 ocular isolates
      of yeast were susceptible to amphotericin B, while two (4%) and five (10%)
      strains were resistant to fluconazole and ketoconazole respectively. Of the 130
      filamentous fungi tested, six (4.6%) were resistant to amphotericin B, 49 (37.7%)
      and 10 (7.6%) were resistant to fluconazole and ketoconazole respectively.
      Percentile 50 (MIC 50) and Percentile 90 (MIC 90) for all the three antifungal
      agents were calculated. Aspergillus niger, Aspergillus terreus and Candida krusei
      were found to be resistant to fluconazole and ketoconazole. CONCLUSION: This
      technique was found to be reliable, cost effective and easy to perform with
      consistent results.

PMID- 17185847
TI  - Serodiagnosis of dengue virus infection in patients presenting to a tertiary care
      hospital.
AB  - Dengue is an acute infectious disease of viral etiology. It is probably one of
      the most important arthropod borne viral disease in terms of human morbidity and
      mortality. The spectrum of disease ranges from self-limited dengue fever to more
      severe forms of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS).
      Laboratory diagnosis of dengue virus infection mainly depends on detection of
      virus specific antibodies. The aim of the study was to correlate the serological
      results with clinical presentation in patients with a diagnosis of dengue. Eleven
      out of 15 (73.3%) patients with DHF and DSS had secondary antibody response and
      mortality was 100% in these patients.

PMID- 17185848
TI  - The clinical and microbiological correlates of premature rupture of membranes.
AB  - Prematurity is the cause of 85% of neonatal morbidity and mortality. Premature
      rupture of the membranes (PROM) is associated with 30-40% of preterm deliveries.
      A case-control study conducted between July 2002 and 2003 examined the correlates
      and risk factors for PROM in Mysore, India. WBCs in vaginal fluid, leucocytes in
      urine, UTI and infection with E. coli, S. aureus, C. albicans and BV were
      significantly associated with PROM. BV, E. coli and WBCs in vaginal fluid were
      independent risk factors. Screening and treatment of BV and E. coli infection in
      pregnancy may reduce the risk of PROM.

PMID- 17185849
TI  - Infective endocarditis due to brucella.
AB  - One of the complications of brucellosis is infective endocarditis, which carries
      a high mortality rate if undiagnosed or misdiagnosed. We report a case of
      Brucella infective endocarditis, which was diagnosed serologically and by
      polymerase chain reaction. After Brucella specific treatment, patient showed
      dramatic improvement clinically, as evident by echocardiogram findings and other
      investigations.

PMID- 17185850
TI  - Necrotizing (malignant) otitis externa: an unusual localization of mucormycosis.
AB  - Malignant otitis externa (MOE) is a severe infection of external auditory canal
      and skull base. A 17-year-old diabetic girl was admitted with diabetic
      ketoacidosis. Cellulitis of her right ear occurred on the second day of
      hospitalization and a black necrotic scar in the same region appeared on the next
      day. The lesion rapidly invaded to right side of neck and surrounding tissue of
      the patient. Therefore, antimycotic therapy was started. Unfortunately the
      patient died on seventh day of hospitalization because of probably extensive
      fungal invasion. Physicians should suspect MOE connected to mucormycosis
      especially in patients with cutaneous lesions of ear unresponsive to antibiotic
      therapy.

PMID- 17185851
TI  - Trichophyton violaceum: a rare isolate in 18-day-old neonate.
AB  - Trichophyton violaceum, a less common and geographically restricted infection is
      reported in a 18-day-old neonate. The diagnosis was made by potassium hydroxide
      of skin scraping examination and confirmed by culture. The patient was treated
      successfully with miconazole nitrate application. A large family with crowded
      living was considered the main predisposing factor.

PMID- 17185852
TI  - Urinary tract infection by Trichosporon asahii.
AB  - Trichosporon asahii is a basidiomycetous yeast which causes white piedra and
      onychomycosis in immunocompetent hosts as well as various localized and
      disseminated invasive infections in immunodeficient hosts. Urinary tract
      infection caused by Trichosporon asahii is rare. One month after posterior
      urethral valve surgery a seven-month-old male child presented with fever, severe
      vomiting and crying on micturition for five--to six days. Yeast-like fungus was
      isolated in pure cultures from three consecutive urine samples. It was identified
      as Trichosporon asahii using standard techniques. The response to antifungal
      therapy was dramatic. To the best of our knowledge this is the first report of a
      urinary tract infection caused by Trichosporon asahii from Western India.

PMID- 17185853
TI  - Disseminated histoplamosis.
AB  - A case of disseminated histoplasmosis in a 45-year-old male patient with acquired
      immunodeficiency syndrome (AIDS) from Pune is reported. The patient presented
      with high-grade fever and pain in hypochondrium. Clinical signs were pallor and
      hepatosplenomegaly. Bone marrow and splenic aspirate revealed numerous
      intracellular oval shaped yeast forms. Histoplasma capsulatum was isolated from
      the bone marrow and splenic aspirate. H. capsulatum infection is an opportunistic
      infection usually reported from patient with AIDS in areas endemic for H.
      capsulatum. The present case highlights the fact that histoplasmosis could be an
      emerging opportunistic infection in India.

PMID- 17185854
TI  - Meningococcaemia: experience at a tertiary care hospital in East Delhi.

PMID- 17185855
TI  - Urinary tract infection due to Arcanobacterium haemolyticum.

PMID- 17185856
TI  - A simple modification of minimum inhibitory concentration determination by E-test
      in the clinical laboratory.

PMID- 17185857
TI  - A preliminary study on the prevalence of leptospira serovars among suspected
      cases of leptospirosis at Tirupati, Andhra Pradesh.

PMID- 17185858
TI  - Detection of biofilm.

PMID- 17185859
TI  - Beta-lactam antibiotic susceptibility testing of MRSA?

PMID- 17185860
TI  - Can donor cornea transmit microsporidial infection?

PMID- 17185861
TI  - Five-year follow-up of hepatitis B surface antigen positive healthy voluntary
      blood donors: a preliminary observation.

PMID- 17185862
TI  - Leptospirosis: current status and future trends.

PMID- 17185863
TI  - Epidemiological patterns of leptospirosis.

PMID- 17185864
TI  - Understanding iron acquisition by pathogenic leptospires: a review.

PMID- 17185865
TI  - Historical perspectives in leptospirosis.

PMID- 17185866
TI  - Recent advances in the laboratory diagnosis of leptospirosis and characterisation
      of leptospires.

PMID- 17185867
TI  - Clinico-epidemiological aspect of leptospirosis in South Gujarat.

PMID- 17185868
TI  - Preventive measures for leptospirosis: rodent control.

PMID- 17185869
TI  - Seroprevalence of leptospirosis in man and animals in Tamilnadu.

PMID- 17185871
TI  - Leptospirosis in Mumbai: post-deluge outbreak 2005.

PMID- 17185870
TI  - Prospects of developing leptospiral vaccines for animals.

PMID- 17185872
TI  - Iron limitation and expression of immunoreactive outer membrane proteins in
      Leptospira interrogans serovar icterohaemorrhagiae strain lai.

PMID- 17185873
TI  - Early diagnosis of human leptospirosis by antigen detection in blood.

PMID- 17185874
TI  - A two-year study of the efficacy of azithromycin in the treatment of
      leptospirosis in humans.

PMID- 17185875
TI  - Evaluation of recombinant Leptospira interrogans serovar canicola outer membrane
      proteins as diagnostic antigen.

PMID- 17185876
TI  - Seroprevalence of leptospirosis in high risk groups in Calicut, North Kerala,
      India.

PMID- 17185877
TI  - Long-term effect of combination therapy with mitiglinide and once daily insulin
      glargine in patients who were successfully switched from intensive insulin
      therapy in short-term study.
AB  - We have previously reported the therapeutic efficacy of mitiglinide combined with
      once daily insulin glargine (mitiglinide regimen) after switching from multiple
      daily insulin regimen of aspart insulin and glargine (intensive insulin regimen)
      in inpatients with type 2 diabetes mellitus in two consecutive days. In the
      present study, we followed up 9 of the 15 responsive patients with these novel
      regimens for 6 months after discharge. The data collected from these patients
      were compared to those of 15 randomly chosen patients who had well matched
      background and received intensive insulin regimen during hospitalization which
      was continued after discharge. The average HbA1c level of these 9 patients with
      mitiglinide regimen at 6 months was 6.7 +/- 0.8% and was comparable to that of
      the patients with intensive insulin regimen (HbA1c = 7.0 +/- 1.0%). In
      conclusion, mitiglinide and insulin glargine combination therapy maintained fair
      glycemic control for as long as 6 months in subpopulation of Japanese patients
      with type 2 diabetes.

PMID- 17185878
TI  - Changes in serum sex hormone profiles after short-term low-dose administration of
      dehydroepiandrosterone (DHEA) to young and elderly persons.
AB  - In man, serum concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate
      (DHEAS) decrease with age after the twenties. For this reason, the decline in
      DHEA and DHEAS concentrations may be related to the development of some chronic
      diseases that are prevalent in the older age population. In this study, we
      evaluate the benefit and safety level of DHEA administration to men as a hormone
      replacement therapy. Twenty-two healthy Japanese males (age 26-63; mean +/- SD,
      41.0 +/- 10.0 yrs.) received 25 mg DHEA once a day orally in the morning for two
      weeks. Serum concentrations of steroid hormones and cytokines were measured
      before and after the DHEA administration. Glucose tolerance and insulin
      resistance were also assessed before and after the DHEA administration using a 75
      g oral glucose tolerance test and homeostasis model assessment (HOMA-R),
      respectively. Serum DHEA and DHEAS levels were significantly elevated after the
      DHEA administration for all ages of test subjects. In subjects who were older
      than 41 yrs. (older group) serum androstenedione and estradiol levels were
      elevated after the DHEA administration. Significant negative correlations were
      observed between the serum DHEA concentration and the serum concentration of
      fasting insulin, HOMA-R, leptin, and high-sensitivity C-reactive protein for all
      subjects. Daily administration of 25 mg DHEA increased the serum DHEA, DHEAS,
      androstenedione, and estradiol levels of the subjects of the older group to the
      same level as that of younger subjects.

PMID- 17185880
TI  - Radioprotective effects of hawthorn fruit extract against gamma irradiation in
      mouse bone marrow cells.
AB  - The radioprotective effect of hawthorn (Crataegus microphylla) fruit extract
      against genotoxicity induced by gamma irradiation has been investigated in mouse
      bone marrow cells. A single intraperitoneal (ip) administration of hawthorn
      extract at doses of 25, 50, 100 and 200 mg/kg 1h prior to gamma irradiation (2
      Gy) reduced the frequencies of micronucleated polychromatic erythrocytes
      (MnPCEs). All four doses of hawthorn extract significantly reduced the
      frequencies of MnPCEs and increased the PCE/PCE+NCE ratio (polychromatic
      erythrocyte/ polychromatic erythrocyte + normochromatic erythrocyte) in mice bone
      marrow compared with the non drug-treated irradiated control (p < 0.02-0.00001).
      The maximum reduction in MnPCEs was observed in mice treated with extract at a
      dose of 200 mg/kg. Administration of amifostine at dose 100 mg/kg and hawthorn at
      dose 200 mg/kg reduced the frequency of MnPCE almost 4.8 and 5.7 fold;
      respectively, after being exposed to 2 Gy of gamma rays, compare with the
      irradiated control group. Crataegus extract exhibited concentration-dependent
      activity on 1,1-diphenyl 2-picrylhydrazyl free radical showing that Crataegus
      contained high amounts of phenolic compounds and the HPLC analysis determined
      that it contained chlorogenic acid, epicatechin and hyperoside. It appeared that
      hawthorn extract with antioxidant activity reduced the genotoxicity induced by
      gamma irradiation in bone marrow cells.

PMID- 17185879
TI  - Short-term effects of atorvastatin on bone turnover in male patients with
      hypercholesterolemia.
AB  - No consensus has been reached on whether the 3-hydroxy 3-methylglutaryl coenzyme
      A (HMG-CoA) reductase inhibitors, known as statins, have beneficial effects on
      bone health. The purpose of our study was to evaluate the effects of atorvastatin
      on bone metabolism by means of measuring bone turnover markers in male patients
      with hypercholesterolemia both at diagnosis and prospectively after 3 months of
      treatment. Twenty-two Japanese male patients (mean age 62.36 +/- 10.1 years) with
      untreated hypercholesterolaemeia were selected for this study. After 3-months
      treatment of atorvastatin, total cholesterol and low density lipoprotein
      cholesterol significantly decreased as expected (p<0.001 for both parameters).
      Bone-specific alkaline phosphatase (BAP) did not change significantly (p =
      0.444). However, serum N-terminal telopeptide of type I collagen (NTx)
      significantly decreased by -19.86 +/- 26.4% (p = 0.020). In addition, delta NTx
      during the course of this study was negatively correlated with NTx at baseline (r
      = -0.645, p = 0.0008). Although there was a tendency of positive correlations of
      delta NTx with delta total cholesterol, delta triglycerides, and delta low
      density lipoprotein cholesterol, and of negative correlations of delta NTx and
      delta BAP with delta high density lipoprotein cholesterol, none of them reached
      statistical significance. Our findings suggest that atorvastatin may have
      potentially beneficial effects on bone metabolism in patients with
      hypercholesterolemia mostly by reducing bone resorption rather than by
      stimulating bone formation. Further studies with more patients and longer
      duration are warranted to evaluate its effects, if any, on prevention of
      osteoporosis and subsequent fractures.

PMID- 17185881
TI  - Final report of the Japan Neurotrauma Data Bank project 1998-2001: 1,002 cases of
      traumatic brain injury.
AB  - A 4-year study (Japan Neurotrauma Data Bank) of the medical treatment of 1002
      cases of traumatic brain injuries in Japan was conducted from 1998 to 2001 at 10
      emergency medical centers. Patients with severe head injury were eligible for
      entry with a Glasgow Coma Scale score of 8 or less at admission. Patients who
      underwent craniotomy were also included. Children under 5 years old were
      excluded. An original data sheet with 392 items from multi-focal viewpoints, such
      as etiology of injury, pre-hospital care, initial treatment including neuro
      intensive care unit, and surgical treatment, was created. The results show that
      the patient's age and mechanism of injury are the most important factors in the
      outcome.

PMID- 17185882
TI  - Distal anterior cerebral artery aneurysms: report of 26 cases.
AB  - Distal anterior cerebral artery (ACA) aneurysms are rare, and constitute
      approximately 1.5% to 9% of all intracranial aneurysms. They show some unique
      features compared with other aneurysms in the cerebral circulation and are
      frequently treated with a different technique. Twenty-six of 364 patients with
      cerebral aneurysms treated at our department between 1996 and 2004 had distal ACA
      aneurysms (7.1%). Twenty-three of the 26 patients were treated through an
      anterior interhemispheric approach and two with a pterional approach. All
      saccular aneurysms were successfully clipped except one which was embolized after
      the surgery. The only fusiform aneurysm spontaneously thrombosed and resolved
      with parent artery occlusion. Two of the 26 patients had multiple aneurysms. The
      surgical mortality was 8%. Distal ACA aneurysms have higher mortality and
      morbidity than other anterior circulation aneurysms. They should be aggressively
      treated even if very small because of the tendency to rupture. Endovascular
      treatment is an alternative in the management of these aneurysms. The most
      important factors affecting the outcome are grade on admission and the
      neurosurgeon's experience.

PMID- 17185883
TI  - Perfusion-weighted magnetic resonance imaging of the spinal cord in cervical
      spondylotic myelopathy.
AB  - Principles of echo shifting with a train of observations was used to perform
      magnetic susceptibility-weighted magnetic resonance imaging with bolus-tracking
      in 14 patients with spondylotic myelopathy to assess changes in perfusion
      parameters of the spinal cord before and after decompression surgery for cervical
      spondylotic myelopathy. The mean transit time (MTT), bolus arrival time (T0), and
      time to peak (TTP) were obtained from regions of interest (ROIs) and assessed as
      the ratio between the spinal cord and the pons (MTT index = MTT(ROI)/MTT(pons),
      T0 index = T0(ROI)/T0(pons), TTP index = TTP(ROI)/TTP(pons)). The patients were
      divided into two groups according to percentage improvement on the Neurosurgical
      Cervical Spine Scale. The MTT index in patients with good recovery (> or =50%)
      was significantly reduced. The T0 index and TTP index showed no significant
      change in both groups. Reduction of MTT index may indicate improved perfusion of
      the spinal cord following surgery for cervical spondylotic myelopathy.

PMID- 17185884
TI  - Cerebral venous sinus thrombosis associated with iron deficiency: two case
      reports.
AB  - Two patients presented with cerebral venous sinus thrombosis (CVST) associated
      with iron deficiency. A 14-year-old man had thrombosis extending from the end of
      the superior sagittal sinus to the left transverse sinus. Severe dehydration
      after competitive sport had induced CVST. The laboratory findings showed severe
      iron deficiency anemia which persisted for 1 year. A 47-year-old man had
      thrombosis in the entire superior sagittal sinus. Dehydration caused by poor
      nutrition had induced CVST. The laboratory findings showed transient iron
      deficiency in the acute phase. Both patients received conservative treatment for
      dehydration and iron supplementation. These two cases indicate that iron
      deficiency is a risk factor for CVST.

PMID- 17185885
TI  - Pituitary apoplexy manifesting as diffuse subarachnoid hemorrhage.
AB  - A 46-year-old woman presented with hemorrhage from a non-functioning pituitary
      adenoma manifesting as sudden onset of severe headache. Computed tomography
      demonstrated diffuse subarachnoid hemorrhage (SAH) and a suprasellar mass with
      intratumoral hematoma. The patient underwent transnasal transsphenoidal removal
      of the pituitary adenoma. This type of SAH with intratumoral hematoma simulates
      rupture of an anterior cerebral artery aneurysm.

PMID- 17185886
TI  - Ectopic recurrence of craniopharyngioma.
AB  - A 27-year-old woman presented with ectopic recurrence manifesting as an
      asymptomatic mass in the left frontal convexity 5 years after subtotal removal of
      suprasellar craniopharyngioma through a right orbitozygomatic craniotomy. The
      mass had enlarged gradually over the next 5 years, so a second operation was
      performed for total removal. The histological diagnoses of both lesions were
      adamantinomatous type craniopharyngioma with MIB-1 indexes of 4.2% and 7.4%. The
      second lesion probably resulted from dissemination. Craniopharyngioma is a benign
      tumor, and ectopic recurrence is rare. Long-term clinical and neuroimaging follow
      up is recommended.

PMID- 17185887
TI  - Spontaneous regression of a growing vestibular schwannoma.
AB  - A 75-year-old woman presented with a small right vestibular schwannoma which
      enlarged and then spontaneously regressed during conservative management. The
      tumor increased in size from 5.2 to 16.7 mm over 7 years with worsening symptoms
      of tinnitus, dizziness, and headache. The tumor then regressed to 8.2 mm and the
      symptoms improved for 4 years without further treatment. Changes in tumor growth
      should be carefully monitored during conservative management of patients with
      vestibular schwannoma.

PMID- 17185888
TI  - Third ventricular chordoid glioma with unusual aggressive behavior.
AB  - A 50-year-old woman presented with a rare chordoid glioma manifesting as an
      approximately 4-year history of decreased cognitive function and recent decreased
      visual acuity. Magnetic resonance imaging showed a 4.5 x 3.5 cm multilobulated
      strongly enhanced mass in the suprasellar cistern and third ventricle associated
      with hydrocephalus. The tumor was subtotally removed via a transcallosal
      approach. Histological examination showed chordoid glioma. Two months later,
      ventriculoperitoneal shunting was performed for hydrocephalus. The tumor and
      hydrocephalus recurred after 3 months. She died after 4 months because of
      deepened mentality and combined pneumonia. This very short duration before
      recurrence suggests that neuroimaging follow up may be necessary in patients with
      subtotally removed choroid glioma.

PMID- 17185889
TI  - Skull metastases from atypical pulmonary carcinoid tumor in a 19-year-old man.
AB  - A 19-year-old man presented with a rare skull metastasis from atypical pulmonary
      carcinoid tumor (APCT) manifesting as headache, diplopia, and cough. Head
      magnetic resonance imaging showed a skull base tumor extending from the posterior
      clinoid process to the clivus, and calvarial tumors in the right temporal and
      occipital bones. Chest and abdominal computed tomography showed a round tumor, 4
      cm in diameter, in the lower lobe of the right lung and multiple small tumors in
      the liver. Surgery for the calvarial tumor in the right temporal bone was
      performed on June 27, 2003. The histological diagnosis was skull metastasis of
      neuroendocrine tumor. Gamma knife radiosurgery was performed for the residual
      skull metastases. Partial resection of the right lower lobe was performed for the
      lung tumor on August 22, 2003. The histological diagnosis was atypical carcinoid
      tumor. Subsequent adjuvant systematic chemotherapy was performed. The patient
      died of progression of the tumors in the lung and liver on April 19, 2004. We
      must consider APCT in the differential diagnosis of pulmonary tumors in
      adolescents, and perform follow-up observation or treatment, including surgery,
      if APCT is suspected.

PMID- 17185890
TI  - Endodermal cyst ventral to the lower brain stem.
AB  - A 28-year-old woman presented with a rare case of endodermal cyst located ventral
      to the lower brain stem manifesting as recurrent aseptic meningitis. Computed
      tomography and magnetic resonance imaging demonstrated a cystic mass located
      ventral to the lower brain stem and extending from the prepontine to the upper
      cervical (C-2) cistern. The lesion was totally removed through a retrosigmoid
      craniotomy and C1-2 hemilaminectomy. Histological and immunohistochemical
      examination showed the cyst was derived from the endoderm. The histological
      diagnosis was endodermal cyst. Early diagnosis and surgical removal are important
      for patients with these cysts.

PMID- 17185891
TI  - Serum resistin increases in a postprandial state during liquid meal challenge
      test in healthy human subjects.
AB  - The role of resistin in humans is controversial although resistin has been linked
      to atherosclerotic and inflammatory processes. In rodents, resistin expression is
      suppressed after food restriction while central administration of resistin
      promotes short-term satiety. However, the nature of postprandial responses in
      circulating resistin in humans is unknown. Therefore, we investigated
      postprandial resistin concentrations in a pilot study in 19 healthy subjects and
      19 controls matched for age and body mass index (BMI). Serum resistin, insulin
      and non-esterified fatty acids (NEFA) concentrations as well as plasma glucose
      and triglycerides were repeatedly assessed before and after ingestion of an
      isocaloric standardized liquid meal during a 300 min period.After consumption of
      liquid meal, serum resistin levels increased compared to fasting control
      (p=0.037). Postprandial plasma glucose and serum insulin increased (p<0.001) with
      lower glucose responses in females (p=0.001) and lower insulin responses in males
      (p=0.012). Plasma triglycerides increased and serum NEFA decreased with similar
      gender responses (p=0.025 and p<0.001, respectively). Serum resistin was not
      correlated to glucose, insulin, triglyceride, and NEFA responses to liquid meal
      challenge tests. The present data suggest that serum resistin increases
      postprandially in healthy humans. Additional studies are needed to elucidate
      normal 24-h daytime profiles in humans and differential response of serum
      resistin to macronutrient composition of meals.

PMID- 17185892
TI  - Significance of the RET proto-oncogene polymorphisms in Turkish sporadic
      medullary thyroid carcinoma patients.
AB  - Several single nucleotide polymorphisms (SNP) of the RET gene have been
      identified in medullary thyroid carcinoma (MTC) patients as well as in the
      general population. However, the relevance of SNP for MTC patients is still
      controversial, whether these allelic variants play other interacting,
      predisposing or modifying roles in clinical behavior of MTC. The aim of this work
      is to elaborate allelic frequencies of the RET proto-oncogene polymorphisms in
      Turkish sporadic MTC patients and to demonstrate if there is an association
      between SNP and the clinical disease features, specifically the age at onset of
      MTC and lymph node involvement at diagnosis. We analyzed the allelic frequencies
      of SNP of the exon 11, 13, 14 and 15 of the RET proto-oncogene in blood samples
      from 50 sporadic MTC patients, using the polymerase chain reaction methodology
      followed by DNA sequencing. The observed allelic frequencies were 24% for G691S
      polymorphism in exon 11, 29% for L769L polymorphism in exon 13, 5% for S836S
      polymorphism in exon 14, and 26% for S904S polymorphism in exon 15. These
      frequencies are similar to those reported in other countries. We did not observe
      any significant association of all four SNP with the age at onset of MTC. Our
      results indicate a possible association between the presence of lymph node
      involvement at the time of diagnosis (extent of disease) and L769L or S836S
      polymorphism. However, it is not possible to draw definitive conclusions that
      these two polymorphisms play a significant role in clinical behavior of MTC.
      Further studies are needed to evaluate the role of this polymorphism in the
      clinical behavior of MTC.

PMID- 17185894
TI  - Evaluation of goiter using ultrasound criteria: a survey in a middle
      schoolchildren population of a mountain area in Central Italy.
AB  - Iodine deficiency is still an important health care problem in the world. In
      Italy, as in most European countries, it is responsible for the development of
      mild to moderate endemic goiter. In 1995 we conducted a goiter survey in the
      Gubbio township, an area of Umbria region in Italy, close to the Appenine
      mountain chain. This study demonstrated a high prevalence of goiter in the middle
      schoolchildren population, indicating the presence of moderate endemic goiter.
      Soon after, a goiter prevention campaign aimed at implementing the consumption of
      iodinated salt was started. In 2001, a second survey was conducted in the middle
      schoolchildren (age 11-14 yr old) of Gubbio and neighbour townships. Eight
      hundred thirteen subjects were studied. Data obtained in 240 age-matched
      children, studied in the same area in 1995, were used for comparison to monitor
      changes 5 yr after the beginning of iodine prophylaxis. Thyroid volume was
      measured by ultrasonography. Gland volume was expressed in ml. A large population
      living in a iodine-sufficient area, previously reported by others, was used as
      control. Urinary iodine excretion was measured randomly in 20% of the children.
      The overall prevalence of goiter decreased between 1995 and 2001 from 29 to 8%.
      Goiter odds ratio (OR), corrected for age, was 4.0 (95% CI 2.8-5.9) for 1995
      compared to 2001 (p<0.000). Mean thyroid volume in the matched populations was
      7.6+/-2.5 ml in 1995 and 5.7+/-2.1 ml in 2001. Median iodine urinary excretion
      increased from 72.6 to 93.5 mug/l, at the limit of statistical significance.
      Living in a rural area, no consumption of iodized salt and familiarity for goiter
      represented independent risk factors for goiter development. This study was the
      first conducted in Umbria region and confirmed that an implementation campaign
      for iodized salt consumption is a simple and useful instrument to prevent endemic
      goiter and related diseases. A new survey to evaluate goiter prevalence in the
      same area 10 yr after the beginning of iodine prophylaxis is already planned.

PMID- 17185893
TI  - Overfeeding-induced weight gain suppresses plasma ghrelin levels in rats.
AB  - The elevation of plasma ghrelin associated with weight loss has been taken as
      evidence of a role for ghrelin in the adaptive response to body weight change.
      However, there has been no clear experimental evidence that circulating ghrelin
      is suppressed by weight gain. We investigate this issue using a model of
      involuntary (intra-gastric gavage) overfeeding-induced obesity. Rats were first
      maintained at normal body weight with 4 daily tube-feedings of liquid diet (2.11
      kcal/ml), each delivered at a volume of 9 ml. Gavage volume was then increased to
      13 ml/feeding for 2 weeks, during which rats gained 25% of their initial body
      weight. Fasting plasma ghrelin levels and the response to 9- and 13-ml intra
      gastric load sizes were measured during the weight-stable and overfed conditions.
      We found that: 1) weight gain decreased circulating ghrelin levels; 2) this
      response could not be attributed to additional food in the gastrointestinal
      tract; 3) the ghrelin response to nutrient loads was diminished in the obese vs
      normal-weight conditions. Having discounted diet composition and differences in
      gastric contents at the time of blood sampling, the decrease in ghrelin levels
      with overfeeding can be unambiguously attributed to physiological correlates of
      weight gain.

PMID- 17185895
TI  - Effects of percutaneous laser ablation treatment in benign solitary thyroid
      nodules on nodule volume, thyroglobulin and anti-thyroglobulin levels, and
      cytopathology of nodule in 1 yr follow-up.
AB  - OBJECTIVE: To investigate the effects of ultrasound (US)-guided percutaneous
      laser ablation (PLA) in the treatment of benign solid hypoactive thyroid nodules
      on nodule volume, thyroid functions, nodule cytology and patients' complaints.
      MATERIAL AND METHOD: Criteria for enrollment in the study were as follows:
      patients with euthyroid, benign, hypofunctional nodule who had compressive
      symptoms or cosmetic complaints, but considered inoperable, or who rejected
      surgical treatment. PLA procedure at 3-5 watts (W) was applied to 15 thyroid
      nodules of 12 patients (4 male and 8 female; age range 20-78 yr, mean age 47.42+/
      17.05 yr), and patients were followed up for 12 months. Thyroid functions and
      nodule volumes (ultrasonographically) were evaluated. US-guided fine needle
      aspiration biopsy (FNAB) was performed before and after the procedure, and biopsy
      specimens were cytologically evaluated. RESULTS: The mean nodule volume before
      the procedure was 11.97 ml (min-max 0.95-26.30 ml). However, 12 months after the
      procedure the mean nodule volume was 2.21+/-2.32 ml (min-max 0.10-7.65 ml). The
      mean reduction in nodule volumes was 82%. Thyroglobulin levels reached peak
      values at 1 month after the procedure, and anti-thyroglobulin levels at 3 months
      after the procedure. FNAB performed at 12th month showed neutrophil polymorphs,
      macrophages, abundant cell debris, colloid, multinucleated giant cells, and small
      fragments of fibrous stroma which indicated that PLA procedure led to
      degenerative changes in nodules. CONCLUSION: US-guided PLA is a new, successful
      treatment method which is reliable in the long term in benign solid thyroid
      nodules for selected patients who are inoperable or do not prefer surgery.

PMID- 17185896
TI  - Linear growth and body mass index in pediatric patients with Cushing's disease or
      simple obesity.
AB  - BACKGROUND: Increasing prevalence of childhood obesity has resulted in an
      accelerating rate of referrals of overweight patients to pediatric clinics for
      exclusion of endocrine or metabolic etiologies. The exclusion of Cushing's
      disease (CD) requires complex and potentially invasive investigations. OBJECTIVE:
      To evaluate the sensitivity of accurate measurements of height, weight and body
      mass index (BMI) in discriminating between simple obesity and CD. METHODS AND
      PATIENTS: Height, weight and BMI were measured at diagnosis in 25 patients with
      CD; 14 males, 11 females, mean age 12.9 yr (6.4-17.8) and 41 patients with simple
      obesity (SO), defined as BMI >2.0 SD; 20 males, 21 females, mean age 9.4 yr (3.5
      15.6). RESULTS: Mean (+/-SE) BMI SDS in the CD patients was 2.41+/-0.5 and in the
      SO patients 3.71+/-1.3. Height SDS in the CD patients was -1.88+/-0.24 and in the
      SO patients 1.18+/-0.19 (p<0.05). The mean (+/-SE) BMI SDS to height SDS ratio
      was significantly decreased in the CD compared with the SO patients; -1.81+/-0.54
      vs +0.90+/-1.17 (p<0.0001). CONCLUSIONS: Simple, accurate measurement of height
      and BMI SDS values provides a quick, and sensitive diagnostic discriminator in
      pediatric patients with CD or SO, thus potentially avoiding complex
      investigations.

PMID- 17185898
TI  - Several mutations in the melanocortin 4 receptor gene are associated with obesity
      in Chinese children and adolescents.
AB  - AIM: To screen mutations in the melanocortin 4 receptor (MC4R) in obese and
      normal-weight Chinese children and adolescents. METHODS: Three hundred Chinese
      children and adolescents, including 200 obese and 100 healthy non-obese
      individuals, were evaluated. The coding region of the MC4R gene was amplified by
      polymerase chain reaction (PCR) and sequenced. RESULTS: In obese individuals, we
      detected two novel heterozygous non-synonymous mutations (c.496G>A, resulting in
      Val166Ile; c.929G>A, resulting in Arg310Lys) and a novel heterozygous non-sense
      mutation (c.831T>A, resulting in a premature stop codon Cys277Stop). In both
      obese individuals and controls, a novel heterozygous non-synonymous mutation
      (c.68T>G, resulting in Leu23Arg, 0.5 and 1%, respectively) and the Val103Ile
      polymorphism (c.307G>A, 3 and 2%, respectively) were found. There was no
      difference in alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      triglyceride (TG), cholesterol (CHOL) and whole body insulin sensitivity index
      (WBISI) between obese individuals with and without mutation. The prevalence for
      heterozygous MC4R mutations was 1.5% in the obese. CONCLUSIONS: Two novel
      heterozygous non-synonymous mutations (Val166Ile; Arg310Lys) and a novel
      heterozygous non-sense mutation (Cys277Stop) were detected in Chinese obese
      individuals. Leu23Arg variant might be a polymorphism in the Chinese population.
      There were no differences between clinical and biochemical profiles in the
      heterozygous mutations and the wild type.

PMID- 17185897
TI  - New splicing mutation of MEN1 gene affecting the translocation of menin to the
      nucleus.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a syndrome inherited in an
      autosomal dominant trait caused by the inactivation of the tumor suppressor gene
      MEN1. OBJECTIVE: To communicate a family with a new heterozygous germ line
      mutation in the intronic region of MEN1 gene and to study its influence in the
      menin expression. PATIENTS AND METHODS: We studied 5 members of a family with
      symptomatic hyperparathyroidism (HPT). One of them had also a neuroendocrine
      pancreatic tumor, and 2 had non-functional multinodular cortical adrenal
      hyperplasia compatible with the diagnosis of MEN1. After the mutation was
      identified, HSP92II restriction enzyme was used to determine both zygosity and
      segregation of the mutation. RT-PCR from leukocyte's isolated mRNA and western
      blot from pancreatic tumor tissue were performed. In vitro studies were done in
      Chinese hamster ovary (CHO) cells transfected with reporter minigenes carrying
      the coding regions spanning exon (EX)-intron 9 and EX10 with the mutant and the
      wild type sequences. RESULTS: We identified a heterozygous G-to-T substitution in
      the intron-EX junction (IVS9-1 G>T) of MEN1 gene in the index case and the family
      members. The mRNA from patient's leukocytes was larger (934 bp) in comparison to
      the normal transcript (717 bp). Immunoblot analysis demonstrated that wild type
      (67 kDa) and two additional mutant proteins (approximately 55 and approximately
      90 kDa) were expressed in the pancreatic tissue. The in vitro study showed a 45%
      nuclear localization of the mutated menin signal and a 95% in the wild type
      protein. CONCLUSIONS: We identified a new intronic heterozygous germ line
      mutation (IVS9-1G>T) of MEN1 gene in a family affected by MEN1 syndrome. This
      mutation alters the splice acceptor site of intron 9 that promotes an incorrect
      splicing, generating aberrant proteins without the nuclear localization signals
      necessary for the normal menin translocation to the nucleus.

PMID- 17185899
TI  - Increased lipid peroxidation in adult GH-deficient patients: effects of short
      term GH administration.
AB  - OBJECTIVE: Adult GH deficiency (GHD) syndrome is characterized by increased risk
      of atherosclerosis and hence of cardio- and cerebrovascular mortality. Oxidative
      stress appears to play an important role in early atherogenesis. Oxidized LDL
      represents an important predictor of cardiovascular risk and is mainly
      responsible for oxidative damage of the endothelium. Its concentrations are
      increased in GHD, but the association between this abnormality and oxidative
      stress is still unclear, due to the discordant results yielded by the few
      available studies. DESIGN AND METHODS: In 13 GHD patients, plasma lipid peroxide
      concentrations were measured before and after a 4-month treatment with
      recombinant human GH (rhGH) and compared with those of 13 age- and sex-matched
      controls. In the same subjects, the so-called "lag-time", an index of anti
      oxidant activity and thus of plasma oxidative balance, was also measured using a
      fluorescence kinetics method. RESULTS: Before treatment, peroxide levels were
      significantly higher in patients than in controls (374.0+/-31.52 vs 268.0+/-8.51
      U.C., p<0.01), whereas the lag-time was significantly lower (113.0+/-10.70 vs
      168.0+/-7.80 min, p<0.01). RhGH administration to patients resulted both in a
      significant decrease in lipid peroxide levels (from 374.0+/-31.52 to 336.0+/
      33.17 U.C., p<0.01) and a significant prolongation of lag-time (from 113.0+/
      10.70 to 144.0+/-15.00 min, p<0.01). After treatment, both parameters were no
      longer significantly different in patients and controls. Lag-time and peroxide
      levels at baseline did not show any correlation with IGF-I concentrations in GHD
      patients. After replacement therapy, however, lag-time was positively (r2= 0.62,
      p<0.01), and peroxide levels negatively (r2=0.41, p<0.05), correlated with IGF-I
      levels. CONCLUSIONS: These data support the view that adult GHD syndrome is
      characterized by an unbalance between pro- and anti-oxidant factors with marked
      preponderance of the former. This abnormality, likely contributing to the
      increased atherogenic risk of GHD patients, is corrected by short-term GH
      administration at a dose able to increase, although not to fully normalize, IGF-I
      levels.

PMID- 17185900
TI  - The combined effect of adiposity, fat distribution and age on cardiovascular risk
      factors and motor disability in a cohort of obese women (aged 18-83).
AB  - Obesity is associated with a number of serious diseases and with a degree of
      motor disability, but the extent of the risk and functional derangement within
      the obese population is not yet completely defined. The study aims to evaluate
      the combined effect of degree of adiposity, body fat distribution and age on
      selected cardiovascular risk factors and functional motor disability in a cohort
      of obese women. A multivariate analysis of variance (MANOVA) is employed to show
      the combined impact of body mass index (BMI), waist-to-hip ratio (WHR) and age on
      systolic and diastolic blood pressure (SBP and DBP), total and HDL cholesterol (T
      CH and HDL-CH), coronary heart disease (CHD) risk, leg power output (W, assessed
      with a Margaria test for stair climbing) and subjective general fatigue in a
      cohort of 463 obese women (BMI range 30.2-66.7 kg/m2; age range 18-83 yr). High
      WHR and older age, but not BMI, are to a variable degree related to unfavorable
      values of parameters which contribute to the cardiovascular risk. WHR in the high
      range is associated with significantly higher values of SBP (p<0.001), CHD risk
      scores (p<0.001) as well as lower levels of HDL-CH (p=0.01), while older age is
      significantly associated with higher SBP (p<0.001), T-CH (p<0.001) and CHD risk
      scores (p<0.001). A significant interaction between age and WHR was detected in
      the effect on DBP (p=0.01), the negative role of high WHR values being apparent
      in older women (age > or = 51 yr) but not in younger ones (age < 51 yr). Although
      not significantly related to CHD risk scores, BMI interacted significantly with
      WHR in determining high risk score values (p=0.01), the negative effect of a high
      WHR being apparent in women with a high degree of obesity (BMI > or = 40 kg/m2)
      but not in those with a low one (BMI < 40 kg/m2). In contrast, WHR did not
      significantly affect W, which appeared to be mainly dependent on age (p<0.001)
      and BMI (p<0.001), when considered in terms of unit body mass (BM). Subjective
      global fatigue, however, was unaffected by any of the factors considered. In the
      present cohort of obese women, older age and excessive abdominal fat distribution
      (as assessed by WHR) appear to be significant factors in relation to increased
      cardiovascular disease risk, irrespective of BMI, while older age and higher
      levels of overall adiposity are associated with functional motor derangement
      irrespective of body fat distribution. This suggests that obesity increases
      metabolic risk and induces motor dysfunction by means of different biological
      mechanisms and with a different impact within the obese female population.

PMID- 17185902
TI  - Heterophilic antibodies causing falsely high serum calcitonin values.
AB  - Heterophilic antibodies (HA) may interfere in some immunoassays, causing falsely
      high hormone values, of which practitioners should be aware when measuring
      calcitonin (CT) used as tumor marker for medullary thyroid carcinoma (MTC). We
      studied four patients with thyroid nodules, three of whom underwent surgical neck
      exploration, after an erroneous diagnosis of MTC because of falsely high serum CT
      eventually proved to be due to HA. One patient had a lingual thyroid, two
      autoimmune thyroiditis and the fourth a colloid goiter. The minimal incremental
      CT response to calcium infusion raised our suspicion of possible false high CT
      values due to HA. There was no linearity of the CT values obtained by testing
      serial dilutions of the sera in the CT assay, which employs two monoclonal mouse
      anti-CT antibodies. Addition of normal mouse gamma globulin eliminated the
      interference by HA in the sera of two patients. Serum assayed in a polyclonal
      radioimmunoassay using goat anti-CT antibodies gave normal CT values. Finally,
      incubation of the sera in Heterophilic Blocking Tubes (HBT) eliminated the false
      CT immunoreactivity. A spontaneous change of the CT serum concentrations was
      noticed in three patients over several months, apparently due to changing titles
      of HA. We suggest that, in patients a) whose CT response to calcium or
      pentagastrin infusion is minimal despite high basal CT values, b) with autoimmune
      thyroiditis and c) in whom an unexpected change in serum CT concentrations
      occurs, the possibility of spuriously high CT values because of circulating HA
      should be considered.

PMID- 17185901
TI  - Association of serum undercarboxylated osteocalcin with serum estradiol in pre-,
      peri- and early post-menopausal women.
AB  - OBJECTIVE: We investigated changes in serum concentration of undercarboxylated
      osteocalcin (ucOC), which is a sensitive marker of vitamin K status, and
      association of ucOC concentration with estradiol concentration in pre-, peri- and
      early post-menopausal women. METHODS: The study population consisted of 193 pre-,
      peri- and post-menopausal Japanese women aged 39-66 yr. Serum ucOC concentration
      was measured to assess vitamin K status; serum concentrations of intact
      osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) were measured as
      bone formation markers; and urine concentration of N-telopeptide was measured as
      a bone resorption marker. Serum estradiol and estrone concentrations were
      measured by a highly sensitive radioimmunoassay. Bone mineral density (BMD) was
      measured at the lumbar spine. RESULTS: Serum concentration of ucOC in peri
      menopausal women was significantly (p=0.0005) higher than that in pre-menopausal
      women, while serum OC concentration in post-menopausal women for whom 1 yr had
      passed since menopause was significantly (p=0.0003, p=0.024, respectively) higher
      than the concentrations in pre-menopausal and peri-menopausal women. Serum ucOC
      concentration showed a significant negative correlation with estradiol
      concentration (r=-0.372, p<0.0001) and a significant positive correlation with
      serum FSH concentration (r=0.324, p<0.0001). Serum OC concentration was
      positively correlated with serum FSH concentration (r=0.317, p<0.001).
      CONCLUSIONS: The results showed that the change in ucOC concentration during the
      menopausal transition is different from that in OC concentration. In addition,
      serum ucOC concentration is closely associated not only with FSH concentration
      but also estradiol concentration.

PMID- 17185903
TI  - Two cases of subacute thyroiditis presenting in pregnancy.
AB  - Subacute thyroiditis (SAT) is an extremely rare cause of thyrotoxicosis in
      pregnant women. Untreated, thyrotoxicosis may result in complications, such as
      prematurity and congenital malformations in the fetus. We report two cases of
      first trimester subacute thyroiditis, one mild and one severe. The severe case,
      as demonstrated by laboratory and ultrasound findings, was successfully treated
      with prednisolone. In this case, it was thought that the benefits of
      pharmacological therapy outweighed the risk of potential teratogenesis by the
      medication. In contrast, the milder case was managed conservatively and resolved
      without treatment. These cases illustrate how laboratory and ultrasound findings
      can be used to determine whether treatment should be initiated and, once begun,
      if medication levels need to be adjusted. In both cases, the pregnancies resulted
      in healthy full-term infants.

PMID- 17185904
TI  - Gene analysis of the calcium channel 1 subunit and clinical studies for two
      patients with hypokalemic periodic paralysis.
AB  - Hypokalemic periodic paralysis (HypoPP) is a skeletal muscle disorder in which
      episodic attacks of muscle weakness occur; they are associated with decreased
      serum potassium (K+) levels. Recent molecular approaches have clarified that the
      condition is caused by mutations in the skeletal muscle voltage-gated calcium
      channel 1 subunit (CACNA1S). We describe two unrelated patients with HypoPP,
      followed by their relevant clinical studies and gene analysis. Clinical studies
      included an oral glucose tolerance test (OGTT), food-loading and insulin
      tolerance tests (ITT). For Case 1, serum K+ levels were extremely decreased
      following insulin tolerance testing compared with levels for controls. These
      results support the hypothesis that no efflux of K+ ion occurs in patients
      because of low activity of adenosine triphosphate (ATP)-sensitive K+ channel
      (KATP) channels. Mutational analysis of the CACNA1S gene showed a duplicate
      insertion of 14 base pairs (bp) from 52 to 65 in intron 26, present in the
      heterozygous state in both patients. No other mutations were detected in the
      CACNA1S gene, the muscle sodium channel gene (SCN4A) or the voltage-gated K+
      channel gene (KCN3) of either patient. Further analysis showed that this
      duplicate insertion of 14 bp in intron 26 of the CACNA1S gene was found in 23.7%
      of healthy subjects. K+ dynamics studies are useful for confirming this syndrome,
      while further gene analysis for various ion channels using amplification and
      direct sequencing are required to evaluate the molecular basis of the disorder in
      the individual patient.

PMID- 17185905
TI  - A patient with recurrent hypercortisolism after removal of an ACTH-secreting
      pituitary adenoma due to an adrenal macronodule.
AB  - A 41-yr-old female was referred for signs and symptoms of Cushing's syndrome.
      Cortisol was not suppressed by 1 mg dexamethasone (0.41 micromol/l). Midnight
      cortisol and ACTH were 0.44 micromol/l and 18 pmol/l, respectively. Urinary
      cortisol excretion was 250 nmol/24 h (normal between 30 and 150 nmol/24 h). A
      magnetic resonance imaging (MRI) revealed a pituitary lesion of 7 mm. ACTH and
      cortisol levels were unaltered by administration of human CRH and high-dose
      dexamethasone. Inferior sinus petrosus sampling showed CRH-stimulated ACTH levels
      of 128.4 (left sinus) vs a peripheral level of 19.2 pmol/l, indicating Cushing's
      disease. After 4 months of pre-treatment with metyrapone and dexamethasone,
      endoscopic transsphenoidal resection of an ACTH-positive pituitary adenoma was
      performed. ACTH levels decreased to 2.6 pmol/l and fasting cortisol was 0.35
      micromol/l. Despite clinical regression of Cushing's syndrome and normalization
      of urinary cortisol, cortisol was not suppressed by 1 mg dexamethasone (0.30
      micromol/l). Ten months post-operatively, signs and symptoms of Cushing's
      syndrome reoccurred. A high dose dexamethasone test according to Liddle resulted
      in undetectable ACTH, but no suppression of cortisol levels, pointing towards
      adrenal-dependent Cushing's syndrome. Computed tomography (CT)-scanning showed a
      left-sided adrenal macronodule. Laparoscopic left adrenalectomy revealed a
      cortical macronodule (3.5 cm) surrounded by micronodular hyperplasia. Fasting
      cortisol had decreased to 0.02 micromol/l. Glucocorticoid suppletion was started
      and tapered over 12 months. Symptoms and signs of hypercortisolism gradually
      disappeared. This case illustrates, that longstanding ACTH stimulation by a
      pituitary adenoma can induce unilateral macronodular adrenal hyperplasia with
      autonomous cortisol production.

PMID- 17185906
TI  - A case of ACTH-independent bilateral macronodular adrenal hyperplasia and severe
      congestive heart failure.
AB  - Cortisol secretion in ACTH independent bilateral macronodular adrenal hyperplasia
      (AIMAH) can be regulated by aberrant adrenal receptors. We describe a patient
      with Cushing's syndrome (CS) due to AIMAH and concomitant Class IV congestive
      heart failure (CHF). Clinical testing for the presence of aberrant receptors
      revealed a pronounced serum cortisol (257%) and aldosterone response (212%) to
      the administration of ACTH and a partial serum cortisol (35%) and aldosterone
      (106%) response to upright posture. This suggested the possible presence of
      aberrant hormone receptors for ACTH [melanocortin 2 receptor (MC2-R)],
      vasopressin, catecholamines or angiotensin II (AT-II) on the patient's adrenal
      glands. Adrenal tissue from the patient demonstrated an eight-fold increased
      expression of MC2-R compared to normal adrenal tissue. This increased expression
      was consistent with the increase in cortisol and aldosterone seen in response to
      exogenous ACTH. We propose that the severe CHF resulted in activation of the
      renin-angiotensin system, with an increased production of AT-II. The elevated
      circulating levels of AT-II may have led to increased expression of MC2-R on the
      patient's adrenal glands and increased responsiveness to ACTH. This unusual case
      of CS may elucidate a heretofore unknown mechanism for the development of AIMAH.

PMID- 17185907
TI  - Chemical neuritis after fine needle aspiration biopsy of thyroid nodule.

PMID- 17185908
TI  - [Standardization of diagnosis and management of food allergy].

PMID- 17185909
TI  - [Vasculitis update: Diagnosis and treatment].

PMID- 17185910
TI  - [Central nervous system damage associated with allergy].

PMID- 17185911
TI  - [Lessons from asthma death].

PMID- 17185913
TI  - [Study of recent yearly trend of increase in airborne pollen of Japanese cedar
      and cypress pollen].
AB  - BACKGROUND: Based on epidemiological studies of prevalence, sensitization as well
      as pollen survey, it is presumed that airborne Japanese cedar pollen (JCP) and
      cypress (JCyP) have increased progressively for past 40 years. However, because
      of their large yearly variations, accurate objective and scientific study is
      required to confirm if it is true or not. METHODS: We analyzed the time trends of
      JCP and JCy separately in 11 districts throughout Japan where have records of
      continuous past survey from 1986 to 2005, by regression analysis using net pollen
      count and their 3 and 5 running means. RESULTS: When significant slope of
      regression line (regression coefficient) is assumed as p < 0.05 and R2
      (coefficient of determination) >0.4, significant increase in airborne pollen was
      revealed in the use of 5 point running mean (6 districts of total 11 in JCP and 5
      in JCyP) but not net count or 3 point running mean because of correction of
      statistic error due to large yearly variations. This study suggested that our
      method used for analysis of a recent increase in airborne JCP and JCyP was useful
      and scientific.

PMID- 17185912
TI  - [Trial of isolation of sick house syndrome and unclassified multiple chemical
      sensitivities--Definition of sick house syndrome, and symptoms].
AB  - PURPOSE: This study was designed to clarify the definition of sick house syndrome
      (SHS). METHODS: SHS was defined based on the disease related to habitation as
      follows. 1. The cause of the onset of a disease relates to house. 2. Symptoms
      appear within house. 3. Symptoms will be less serious or disappear if patient
      away from house. 4. If patient goes into house, symptoms will appear repeatedly.
      When it corresponded to all above, it was defined to SHS, and it classified as
      MCS (multiple chemical sensitivities) without above conditions. Even if SHS is
      isolated from similar disease completely, characteristic symptoms of MCS are hard
      to be detected because MCS are combination of two or more diseases. Based on this
      working hypothesis, the logistic regression by setting MCS as reference was
      performed so that characteristic symptoms of SHS show odds ratios with exceeding
      one. RESULTS: The odds ratios with more than two of characteristic symptoms in
      SHS were "nausea or vomiting" "Troublesome in everything" and the causative
      substances to which symptoms get worse was "The smell of a perfume and
      cosmetics". Characteristic symptoms of an allergy disease were detected by
      comparison with the allergic conjunctivitis, allergic rhinitis, and bronchial
      asthma, respectively. CONCLUSION: These results showed that the classification
      method was appropriate. This definition is not fundamentally differed from the
      definition of the sick-building syndrome of WHO.

PMID- 17185914
TI  - [Characteristics of shrimp allergy from childhood to adulthood in Japan].
AB  - OBJECTIVE: We examined profiles and clinical symptoms of shrimp allergy patients
      and investigated the correlation of shrimp-specific IgE to crustaceans-specific
      IgE, mollusks-specific IgE and shellfish-specific IgE. In addition, symptoms when
      eating crustaceans other than shrimp, mollusks and shellfish were examined,
      because they shared tropomyosin as a major allergen. METHODS: We examined 99
      definitive shrimp allergy cases with questionnaire. RESULTS: Their onset started
      during either childhood or young adulthood. Symptoms appeared within an hour
      after ingestion of shrimp in 87.9% cases. The most common symptoms were skin
      symptoms, followed by oral allergic syndrome (OAS) like symptoms, respiratory
      symptoms. Anaphylaxis were observed in 61 cases including 2 anaphylactic shock
      cases. Among 99 shrimp allergy cases, 44 cases (64.7%) showed positive reaction
      to crabs out of 68 cases experiencing crab ingestion. Only 11 cases (17.5%)
      reacted against squid out of 63 cases with the experience in squid ingestion.
      Crab-specific IgE (C.I. 0.954, p < 0.001) and squid-specific IgE (C.I. 0.582, p >
      0.001) were strongly correlated with shrimp-specific IgE. CONCLUSION: We conclude
      that a lot of cases with shrimp allergy react to crabs clinically, and which seem
      to be different from the reaction against mollusk and shellfish intake in spite
      of sharing tropomyosin as a major allergen among them.

PMID- 17185915
TI  - [Investigation of trend in patients with pollinosis using web site: Comparison of
      these three years].
AB  - BACKGROUND: Recently, the number of patient with Japanese cedar pollinosis (JCP)
      has been increasing. In the last 3 years, the amount of pollen has been very
      volatile. In this study, we examined that whether the amount of pollen influenced
      symptoms and selfcare using web site. METHODS: For this examination, the
      questionnaire on web site was used from March 15 to April 30, 2003, 2004, and
      2005 respectively. RESULTS: The rate of early treatments was high in the years
      when the amount of pollen was large, while the rate was low in the years when the
      amount of pollen was little. In the comparison of symptoms, the severity of the
      symptoms, in particular, nasal congestion, itchy eyes, watering eyes, and
      disturbance of sleep, was highly related to the amount of pollen. In addition,
      these symptoms were the severest in 2005. And the selfcare was also changing
      according to the amount of pollen. CONCLUSION: We concluded the greater the
      amount of pollen was, the severer the nasal congestion, eye symptoms, and
      disturbance of sleep were. The questionnaire survey that uses web site is a
      limited investigation of patient who has the access to the Internet. However, in
      the trend survey of JCP patients, it seemed that was extremely meaningful.

PMID- 17185916
TI  - [A case of drug-induced pneumonitis due to amiodarone].
AB  - An 80-year-old man, who had been taking the antiarrhythmic drug amiodarone for
      chronic atrial fibrillation since October 2004, developed dyspnea and fever in
      June 2005, and was admitted to our hospital. Chest X-ray and CT scan showed
      ground-glass opacities in all lung fields. Arterial blood gas analysis revealed
      hypoxemia. These findings led to a diagnosis of acute respiratory distress
      syndrome. Oral amiodarone was discontinued, and steroid pulse therapy was
      started; however, the disease progressed rapidly, and the patient died on the
      fourth hospital day. Autopsy showed diffuse alveolar damage, accumulation of
      edema fluid in the alveolar spaces, and the presence of foamy macrophages,
      leading to a diagnosis of amiodarone-induced pulmonary damage.

PMID- 17185917
TI  - [A case of chrome asthma induced by exposure to the stone cutter dust].
AB  - The case of a forty-six year old, male patient with asthma caused by exposure to
      dust containing chrome is presented. When the patient was nineteen years old, he
      started working as a stonemason in a factory. He cut and ground stone with a
      stone-cutter to make statues and tombstones. Three years after staring to work,
      contact dermatitis was observed on his arms and hands. Within six years of work,
      he suffered from chronic coughing. After eight years, he experienced bronchial
      asthma attacks with wheezing and dyspnea. He had been exposed to dust for eight
      years before developing asthma. The symptoms increased gradually. He fell into
      severe asthma attacks causing unconsciousness and dyspnea. Several common
      therapies were not effective. The characteristics of his clinical course and
      occupational history suggested that the asthma must be caused by exposure to dust
      containing metal generated in the factory. Skin Patch Tests (SPT) were performed
      for cobalt, copper, iron, chrome, tin, and manganese salt. The result of the SPT
      indicated a strong positive result for potassium dichromate and positive for
      chromium sulfate, but did not show any indications in the control or for other
      metallic salt. Fluorescent X-ray analysis detected that chrome was present in the
      powder dust under the stone-cutter machine. However, the fluorescent X-ray
      analysis did not detect chrome in the stone materials. It was suggested that
      chrome must be contained in the metal dust generated from the steel cutter used
      to cut off and grind the stone. The metal component in the used cutter edge and
      the unused cutter edge were analyzed with electro-probe microanalyzer (EPMA). The
      result revealed that chrome was contained in the used, dull cutter edge and not
      in the new sharp cutter edge. Thus, the patient had been exposed to the dust
      containing chrome generated from part of the stainless steel of cutter. He had
      sensitized to chrome and this had caused the occupational chrome-asthma.

PMID- 17185918
TI  - [Adenocarcinomas of the ethmoid sinus: retrospective analysis of prognostic
      factors].
AB  - OBJECTIVES: Determinate the different prognostic factors of survival in ethmoidal
      sinus adenocarcinomas (ADK). MATERIAL AND METHODS: 60 patients with ethmoidal
      sinus ADK. 59 men and one woman. Average of 62.2 years (41-82). Retrospective
      study between 1985 and 2005. The following data were analyzed: exposure time to
      wood dust, disease incidence, primary clinical symptoms and ASA score.
      Radiological data were recovered by tomodensitometry and magnetic resonance
      imaging. Histological groups were described. TNM classification according to UICC
      2002 and Roux/Brasnu was established on clinical and radiological constatations.
      Different treatments used were analyzed. Estimate of survival rate and impact of
      different prognostic factors were based on Kaplan-Meier actuarial method and
      multivariate analysis. RESULTS: Incidence rate was 2.86 patients a year. Exposure
      average time to wood dust was 25.6 years (2-44). T3/T4 stages were predominant
      (66.7%). the survival rate was 46.5% at 5 years. The survival rate was
      significantly superior respectively in T1 and T2 stages than in T3 and T4 stages,
      and in T4a than in T4b stages. Extension of the lesion to the sphenoid sinus was
      revealed as a significant bad prognostic factor. The ASA score and the exposure
      time to wood dust were not identified as statistically significant prognosis
      factors. CONCLUSION: Survival factors of ethmoid sinus ADK were T stage and the
      extension of the tumor to the sphenoid sinus. On the results of this study, we
      consider that extension in sphenoid sinus could be include in TNM classification
      of ethmoid sinus adenocarcinomas.

PMID- 17185919
TI  - [Neck dissection for stage N0 oral cavity carcinoma].
AB  - OBJECTIVES: The management of N0 neck remains controversial. The purpose of this
      study was to evaluate the efficacy of selective neck dissection (SND) in managing
      N0 neck of oral cavity carcinomas. MATERIAL AND METHODS: A retrospective chart
      review of 77 previously untreated patients with squamous cell carcinomas of the
      oral cavity with N0 neck from 1988 to 2001 was performed. Cervical treatments
      were "wait and see" policy in 7 cases, neck dissection in 56 cases, radiotherapy
      alone in 14 cases. 77 neck dissections were performed in which 62 were selective
      and 15 were radical modified. RESULTS: On pathologic examination, the average
      number of lymph nodes was 10.7 per neck. Occult disease (cN0pN+) was detected in
      32.5%, and occult extracapsular spread (cN0pN+R+) was detected in 7.8%. The
      median follow-up was 43 months. The overall neck recurrence rate in patients with
      controlled primary disease was 2.4%. Recurrent disease developed in 2.9% of the
      cNOpN0 neck. Regional control rate of the dissected neck was 94%. No cervical
      recurrence occurred in 11 patients treated with SND alone. There was no survival
      or recurrence rate difference in T1T2pN0 patients with or without post-operative
      radiotherapy. Post-operative radiotherapy could be avoided in 27% of the
      dissected neck. One, 3 and 5 years overall survival rate were 89.3%, 77.7% and
      63.2%. CONCLUSIONS: SND is an effective procedure for staging and treating the
      clinically negative neck of oral cavity cancer.

PMID- 17185920
TI  - [Positron emission tomography in head and neck squamous cell carcinomas].
AB  - 18F-Fluorodeoxyglucose positron emission tomography (PET) is an imaging modality
      which is becoming increasingly esential in oncology, especially in the management
      of head and neck squamous cell carcinomas (SCC). The most common uses of the PET
      are listed in this thematic study: initial staging, cervical lymph node
      metastases from an unknown primary tumor and post-therapeutic follow-up. The
      advantages and drawbacks of this imaging tool are exposed here according to both
      our experience and data from the literature. Decision schemes are suggested for
      each use so as to optimize the use of this imaging modality in the management of
      these SCC. Other fields of application for the PET are mentioned, such as the in
      progress evaluation of response to chemotherapy, the interest of this imaging
      tool in radiotherapy as well as current biochemical developments concerning new
      tracers.

PMID- 17185921
TI  - [Post-therapeutic follow-up in upper airway squamous-cell carcinoma].

PMID- 17185923
TI  - [The role of dermatology in palliative care].

PMID- 17185922
TI  - [Who am I? E...].

PMID- 17185925
TI  - [Palliative care management of patients in a dermatology department].
AB  - BACKGROUND: The number of patients referred to French University dermatology
      departments for skin cancers has increased continuously for many years. The aim
      of this study was to assess the management and number of patients who died in our
      dermatology department over a 10-year period. PATIENTS AND METHODS: All cases of
      patients who died in our dermatology department from 1992 to 2002 were
      retrospectively assessed. Demographic data, past history, main diagnosis,
      duration of hospitalisation and main treatment given were recorded. RESULTS: The
      number of patients who died increased from 9 per year at the beginning of the
      study period to 25 per year at the end of this study. The mean age of patients
      remained unchanged at 66.5 years old. Forty-nine percent of patients in this
      study had metastatic melanoma, with no significant modification during the study
      period. Morphine-based drugs were used (mainly orally) in 41 percent of patients
      at the beginning of the study and in 56 percent (mainly via subcutaneous
      infusions) at the end of the study. Forty-five percent of patients were managed
      in close collaboration with the palliative care unit. CONCLUSION: This study
      showed a three-fold increase in the number of patients referred for end-of-life
      care in a dermatology department during a 10-year period. Most of these patients
      had disseminated malignant melanoma. Major changes in patient management occurred
      during this period.

PMID- 17185924
TI  - [What is the current basis for the diagnosis of pseudoxanthoma elasticum?].

PMID- 17185926
TI  - [Allergy to latex gloves among healthcare workers in Dakar].
AB  - BACKGROUND: The prevalence of latex allergy is high (to 17%) among groups at risk
      such healthcare workers. Our aim was to determine the prevalence and severity of
      allergy to latex gloves among health workers in Dakar. PATIENTS AND METHODS: The
      study was conducted in three of the five hospitals in Dakar (Senegal). A
      randomized sample was constituted. All healthcare workers required to use latex
      gloves in their work were included. A questionnaire was administered. The
      analysis was performed using the Epi-info software package (6.0). RESULTS: One
      hundred and forty cases were included. The median age was 39 years and the sex
      ratio was 0.57. Sixty-six (47%) cases had familial atopic dermatitis, 13 (9.6%)
      had atopic dermatitis, and 4 (2.9%) indicated food allergy (banana, avocado).
      Irritant dermatitis was found in 40.7% of cases, 112 healthcare workers (81.2%)
      used bleach and water to clean their hands. Antiseptics were used frequently:
      75.5% of those interviewed used them more than three times a day. None of the
      healthcare workers indicated any allergy to latex condoms. Otherwise surgical
      procedures and bladder/rectal catheters were noted respectively in 24% and 18%
      cases. Fifteen healthcare workers (10.7%), of whom 12 were women, indicated
      appearance of clinical signs when using latex gloves. The clinical manifestations
      were: contact urticaria or immediate pruritus (8 cases), combined contact
      dermatitis and contact urticaria (2 cases), allergic conjunctivitis (1 case),
      allergic rhinitis (2 cases) and asthma (2 cases). We also noted 6 cases of
      contact dermatitis. Rechallenge tests were performed in 7 cases and were
      positive, 2/3 prick-tests and 1/4 patch-tests (standard European battery). The
      statistical analysis shows that allergy to latex gloves was significantly
      associated with atopy and irritant dermatitis (p<0.03). DISCUSSION: We found a
      prevalence of allergy to latex gloves of 11% among healthcare workers in Dakar,
      reflecting reports in the literature. The classical risk factors such atopic
      dermatitis and irritant dermatitis were found. The correlation between irritant
      dermatitis and frequent use of bleach and water mean that these practices should
      be eradicated since they play an important role in the development of contact
      urticaria and anaphylactic reactions.

PMID- 17185927
TI  - [Erosive pustular dermatosis of the leg: role of zinc deficiency?].
AB  - BACKGROUND: Erosive pustular dermatosis of the legs is a rare and recently
      described condition seen in elderly subjects. It is characterised by symmetric
      erosions of the legs resulting from a confluence of sterile pustules, usually
      following minor trauma. Treatment with dermal corticosteroids is rapidly
      effective but is not codified and relapse is common. CASE-REPORTS: Three patients
      aged respectively 74, 84 and 92 years presented ulcers of the legs and ankles
      associated with peripheral pustules following minor injury. These pustules were
      sterile and exhibited a spongiform appearance on histological examination. None
      of these patients had a prior history of psoriasis. However, all presented zinc
      deficiency. Treatment with dermal corticosteroids combined with oral zinc
      gluconate resulted in complete resolution in two of the patients after several
      days of therapy and proved effective during relapse in the third patient.
      DISCUSSION: Erosive pustular dermatosis of the legs is a benign dermatosis that
      is probably under-reported that should be included in the category of
      inflammatory neutrophilic dermatoses. The cases we present suggest a triggering
      or enhancing role of zinc deficiency.

PMID- 17185928
TI  - [Diagnostic modalities of visceral metastases during follow-up of patients with
      stage I-II melanoma].
AB  - INTRODUCTION: Although not recommended in France at the consensus conference of
      1994, routine monitoring of patients with stage I melanoma using imaging
      techniques is commonly carried out. The aim of this retrospective regional study
      was to define methods for diagnosing transition to the metastatic stage of
      melanoma. PATIENTS AND METHODS: This was a retrospective study based on
      questionnaires among dermatologists in the Champagne-Ardenne and southern Aisne
      regions of France. For each patient with stage IV melanoma between 1987 and 2002,
      data were collected concerning the primary melanoma (date of diagnosis, clinical
      picture, histopathologic features), stage of melanoma prior to diagnosis of
      metastatic melanoma and characteristics of the metastases (date, number, type,
      site and modern discovery: clinical signs or routine imaging). RESULTS: One
      hundred and eight patients (63 men and 45 women; mean age: 59 years) were
      included in the study. The predominant site of the primary melanoma was the trunk
      for men (n=31) and the lower limbs for women (n=16) and the mean Breslow index
      was 4.31 mm (SD=4.22), with histologic ulceration being present in 40% of cases.
      The mean time to transition to stage IV after discovery of the primary tumour was
      2.8 years (SD=2.95). The modes of discovery of metastases comprised clinical
      examination (functional signs or physical examination) in 58 cases and routine
      imaging in 50 cases, with no significant differences based on whether patients
      were initially in stage I-II or in stage III. DISCUSSION: This study shows that
      over half of patients progressing to stage IV melanoma had a suspicious sign or
      clinical symptom, once again highlighting the importance of clinical monitoring.
      In contrast, many organ metastases, particularly pulmonary, were discovered by
      routine imaging examinations carried out as part of patient follow-up, although
      this is not currently recommended practice in France. CONCLUSION: The role of
      powerful imaging examinations such as scans, with constantly improving
      resolution, still remains to be defined in the follow-up of patients with stage I
      II melanoma, and further prospective studies are thus required.

PMID- 17185929
TI  - [Lupus profundus and myelopathy].
AB  - BACKGROUND: We report a case of myelopathy during the course of lupus profundus
      that is unique to our knowledge. CASE-REPORT: A 29-year-old woman had lupus
      profundus since 1999, initially associated with thrombopenia (28,000
      platelets/mm3) treated with corticosteroids for 6 months. Several nodular
      eruptions occurred from 1999 to 2004. Antinuclear antibodies were positive at
      1/320 to 1/640 and complement C4 fraction was low. While being treated with
      hydroxychloroquine for a recent flare-up of nodular lesions of lupus profundus,
      she complained of paraesthesia of the abdominal wall and of the upper and lower
      limbs, suggestive of a medullary lesion. MRI disclosed an image of acute myelitis
      at the level of the second cervical vertebra. High doses of corticosteroids were
      promptly administered intravenously (methylprednisolone bolus) followed by oral
      prednisone and hydroxychloroquine. Six months later the patient was free of
      neurologic or cutaneous symptoms. DISCUSSION: In the literature, systemic signs
      are rarely associated with lupus profundus and myelitis has never been reported.
      Lupus myelitis is a vascular and/or demyelinating and usually segmental lesion of
      the spinal cord. Neurologic symptoms are those of acute rather than chronic or
      recurrent transverse myelitis. The prognosis is poor with frequent and severe
      functional sequelae. Treatment is mainly based on high-dose systemic
      corticotherapy alone or combined with cyclophosphamide. Our patient responded
      favourably to early methylprednisolone bolus followed by oral corticosteroids and
      antimalarial treatment. CONCLUSION: Lupus profundus is classically of benign
      course with only cutaneous involvement, but it may sometimes be a sign of
      systemic lupus and in rare cases may be associated with severe complications.

PMID- 17185930
TI  - [Leiomyosarcoma of the lip].
AB  - BACKGROUND: Superficial leiomyosarcomas are rare malignant tumors that may be
      subdivided into cutaneous and subcutaneous cases. CASE-REPORT: A 58 year-old man
      was seen for a lower lip tumor that appeared 3 years earlier. Histopathologic and
      immunohistochemical examinations showed features of cutaneous leiomyosarcoma.
      DISCUSSION: Cutaneous leiomyosarcoma may derive from the arrector pili, smooth
      muscle of sudoral glands or genital dartoic muscle. The subcutaneous form arises
      from smooth muscle wall of blood vessels. Superficial leiomyosarcomas occur
      frequently in the extensor surface of the lower extremities and involve the
      mucosal area in rare cases. Only five cases arising in the lips have been
      described. Lip cutaneous leiomyosarcoma may derive from ectopic sweat glands of
      the lips or from a hypodermic tumor that extends to the lip.

PMID- 17185931
TI  - [Aggressive T cytotoxic CD8+ epidermotropic cutaneous lymphoma: a case in a
      patient with Steinert's myotonic dystrophy].
AB  - INTRODUCTION: Primary cutaneous "aggressive" CD8-positive epidermotropic
      cytotoxic T-cell lymphoma is a rare subset of cutaneous cytotoxic T/NK lymphomas
      that clearly differs from mycosis fungoides, whether CD4+ or CD8+, by the
      presence of rapidly evolving tumoral cutaneous lesions, foci of keratinocytes
      necrosis, a cytotoxic T phenotype and a poor prognosis. CASE REPORT: A 33-year
      old man with Steinert's myotonic dystrophy was referred for evaluation of rapidly
      worsening cutaneous tumors along with marked deterioration of general status.
      Clinical, histological and immunohistological data led to the diagnosis of
      primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma. CHOP
      chemotherapy was effective despite cardiac toxicity in the setting of Steinert's
      dystrophy, but the patient relapsed and died of pulmonary sepsis after
      chemotherapy was resumed. DISCUSSION: The treatment of primary cutaneous
      epidermotropic CD8+ cytotoxic T-cell lymphoma is not codified. CHOP chemotherapy
      is usually the first-line therapy but relapses are frequent with median survival
      of no more than 34 months. In our patient, an additional difficulty was the
      cardiac toxicity of cytostatic drugs linked to the myopathy which prevented the
      use of high dosages, requiring a change of therapeutic regimen.

PMID- 17185932
TI  - [Multiple verruciform xanthomas of the oral mucosa associated with graft versus
      host disease].
AB  - BACKGROUND: Verruciform xanthoma is an uncommon lesion that occurs primarily on
      the mucous membranes and more rarely on the skin. A few authors have reported the
      extremely rare occurrence of multiple lesions. Triggering or enhancing factors
      have been occasionally described such as an underlying immunosuppression or
      associated inflammatory mucous or skin diseases. We report, to the best of our
      knowledge, the first case report of multiple verruciform xanthomas of the oral
      mucosa in a patient with graft-versus-host disease with specific oral lesions.
      CASE REPORT: A 57 year-old man presented with an 8-year history of chronic
      myeloid leukemia. He was considered in complete remission for leukemia after
      allogenic bone marrow transplantation. Nevertheless, he was still treated with
      immunosuppressive drugs for oral and cutaneous lesions of chronic graft-versus
      host disease. In this context, the patient presented two symmetric lesions of the
      gingiva. These lesions had progressed over several months. The clinical
      presentation was similar, with a yellowish and verrucous aspect and a sessile
      base. Histologic and immunohistochemical analysis led to the diagnosis of
      multiple verruciform xanthomas. DISCUSSION: The occurrence of multiple lesions of
      this rare tumour in our patient was probably not fortuitous. Immunosuppression
      associated with oral chronic inflammatory lesions are certainly involved in the
      pathogenesis of these two verruciform xanthomas, for example following
      degeneration of epithelial cells after local chronic irritation and/or reduction
      of Langerhans cells. Systematic research of enhancing or triggering factors seems
      essential in verruciform xanthoma.

PMID- 17185933
TI  - [Erythema multiforme majus and Chlamydia pneumoniae infection].
AB  - BACKGROUND: Erythema multiforme majus of infectious origin is an acute eruptive
      syndrome seen more commonly in young subjects and characterised by an appearance
      of round target lesions. In most cases, it is associated with infection involving
      Herpes simplex virus or Mycoplasma pneumoniae. We report an original case of
      erythema multiforme majus subsequent to infection with Chlamydia pneumoniae. CASE
      REPORT: An 18 year-old man was hospitalised for management of generalised skin
      rash comprising lesions in rings, associated with bullous and post-bullous
      lesions, chiefly in the oral (preventing eating) and genital areas in a setting
      of febrile cough. Various bacterial agents (Mycoplasma pneumoniae, Chlamydia
      pneumoniae) and viral agents were suspected, but serological testing for
      Chlamydia pneumoniae alone was positive with IgM of 128 IU and IgG of 64 IU. The
      outcome was favourable within several days following administration of
      symptomatic treatment (rehydration, mouthwashes, etc.) and aetiological treatment
      (acyclovir: 30 mg/kg/d, ofloxacine: 400 mg/d). At D15, serologic tests for
      Mycoplasma pneumoniae continued to be negative. Anti-Chlamydia pneumoniae IgM and
      IgG were 256 IU. At D30, IgM was 128 IU while IgG remained at 256 IU. DISCUSSION:
      The existence of a systematic skin rash comprising typical target lesions and
      mucosal lesions in the oral and genital areas suggested to us a diagnosis of
      erythema multiforme majus. Screening for the agents generally responsible was
      negative and drug-induced rash was ruled out. Serological tests for Chlamydia
      pneumoniae were positive at various times, resulting in diagnosis of erythema
      multiforme majus secondary to infection with Chlamydia pneumoniae. Following
      demonstration of the presence of Chlamydia pneumoniae using reliable methods and
      the elimination of other causes of erythema multiforme majus, dermatologists
      should opt for this aetiology in order to optimise treatment.

PMID- 17185934
TI  - [Malignant nodular hidradenoma and multiple nodular hidradenomas in a hypogonadic
      patient].
AB  - BACKGROUND: We report a case of multiple benign nodular hidradenomas associated
      with malignant nodular hidradenoma in a hypogonadic patient. CASE-REPORT: A 49
      year-old man presented 11 benign nodular hidradenomas in the pectoral region. A
      malignant nodular hidradenoma had recently appeared in this region some distance
      from the pre-existing benign modular hidradenomas. This patient had peripheral
      hypogonadism associated with congenital bilateral cryptorchidia responsible for
      gynecomastia due to "relative hyperestrogenism". Large numbers of estrogen
      receptors were demonstrated in each of the benign nodular hidradenomas. The
      malignant nodular hidradenoma mass was unavailable and screening for these
      receptors was not possible. DISCUSSION: Cases of multiple nodular hidradenoma are
      extremely rare: we have seen only two. To the best of our knowledge, there have
      been no reports to date of combined malignant nodular hidradenoma and multiple
      benign nodular hidradenoma. However, there is histological evidence of transition
      forms. The coexistence of endocrine anomalies associated with this type of tumour
      has never been reported. However, the presence of estrogen receptors has
      occasionally been demonstrated in benign nodular hidradenomas. Our patient's
      endocrine disease may have played a role in the presentation of multiple
      hidradenomas, but this cannot be demonstrated.

PMID- 17185935
TI  - [Ingrown nails: a complication of surgery for an in-growing toe-nail using the
      Zadik procedure].

PMID- 17185936
TI  - [Paroxetine (Deroxat and spontaneous ecchymosis].

PMID- 17185937
TI  - [Epidermal cysts caused by implantation].

PMID- 17185938
TI  - [Pemphigus: treatment and outcome in 122 cases].

PMID- 17185939
TI  - [An erosive lesion of the nipple].

PMID- 17185940
TI  - [Clinical appearance and management of cutaneous side effects of EGF receptor
      inhibitors].

PMID- 17185941
TI  - [Folliculitis with cicatricial alopecia].

PMID- 17185942
TI  - [Compound nevus].

PMID- 17185943
TI  - [The MAP-kinase pathway in genodermatosis: new developments].

PMID- 17185944
TI  - [Paraneoplastic acrokeratosis (Bazex syndrome)].

PMID- 17185945
TI  - [Posttraumatic meningitis: incidence, bacteriology, and outcomes].
AB  - BACKGROUND AND PURPOSE: The aim of our study was to search for the incidence, the
      responsible organisms and the favoring causes of death of post-traumatic
      meningitis (PTM). METHODS: This retrospective study was conducted over a seven
      year period (January 1st, 1996 - December 31, 2002) in the ICU and the
      neurosurgery department of the Habib-Bourguiba University Hospital, Sfax,
      Tunisia. RESULTS: Over the study period, 38 patients presented PTM (0.96% of
      patients hospitalized for head injury), 92% of them had received antibiotic
      prophylaxis on admission. Mean time between head injury and the diagnosis of PTM
      was 9+/- 8 days (range: 2-34 days). The most common isolated organisms were
      multidrug resistant A. baumanii, and K. pneumoniae and reduced susceptibility S.
      pneumoniae. Factors predictive of prognosis in the 14 days following the
      diagnosis of meningitis were Glasgow coma score (GCS) on the day of diagnosis of
      PTM, absence of nuchal rigidity, CSF protein, CSF/blood glucose ratio, and S.
      pneumoniae as the causal agent of PTM. CONCLUSIONS: Antibioprophylaxis in
      patients with head trauma must be avoided to prevent the emergence of multidrug
      resistant bacteria when PTM occurs. GCS on the day of diagnosis of PTM, CSF
      protein concentration, CSF/blood glucose ratio, and S. pneumoniae as the causal
      agent of PTM are predictive factors of mortality of patients with PTM.

PMID- 17185946
TI  - Lhermitte-Duclos disease and Cowden's syndrome. Report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: Lhermitte-Duclos disease, or dysplastic cerebellar
      gangliocytoma is a rare entity characterized by a hamartomatous lesion in the
      posterior fossa. Cowden's syndrome, or hamartoma-neoplasia syndrome is a rare
      underdiagnosed autosomal dominant genodermatosis with high incidence of malignant
      tumors. Several recent reports suggest that Lhermitte-Duclos disease may be a
      component of Cowden's syndrome. CLINICAL PRESENTATION: We report two cases of
      Lhermitte-Duclos and Cowden disease occurring in adult patients. A 40-year-old
      woman had symptoms of raised intracranial pressure and macrocephaly. She
      displayed the stigmata of fibrocystic breast disease, thyroid goitre. Clinical
      examination showed mucocutaneous lesions. Her mother, brother and uncle had
      manifestations of Cowden's disease. An asymptomatic 38-year-old male had
      bilateral optic nerve drusen related to a cerebellar neoplasm. He exhibited
      manifestations of Cowden's syndrome and his familial history confirmed this
      hypothesis. INTERVENTION: The first patient was operated on for Lhermitte-Duclos
      disease. A conservative strategy was performed for the second patient and the
      clinical and imaging follow-ups were uneventful over 5 years. CONCLUSION: We
      stress the possibility that Lhermitte-Duclos and Cowden disease might be a
      peculiar form of phakomatosis. A conservative strategy can be chosen without
      neurological signs because of slow tumor growth. However, these patients should
      be carefully examined and followed up because of the risk of future malignancy.

PMID- 17185947
TI  - Histologically malignant solitary fibrous tumor of the orbit.
AB  - An intra-conical histologically malignant solitary fibrous tumor of the orbit
      presented in a 28 year-old female with intact vision and exophthalmos. Total
      resection was achieved by means of a frontal craniotomy and orbital roof
      osteotomy. Evidence of a beneficial role for adjuvant treatments in this
      particular tumor is controversial and vision impairment is a possible side
      effect. Therefore they were not employed. The patient is well after two years of
      follow-up.

PMID- 17185948
TI  - [Value of retrolabyrinthine approach for surgical resection of meningiomas
      inserted around the lateral sinus between the transverse and sigmoid parts].
AB  - PURPOSE: To describe the retrolabyrinthine approach for the resection of 9
      meningiomas inserted around the lateral sinus between the transverse and sigmoid
      parts, to discuss the value of this approach compared to the retrosigmoid
      approach for resection of meningioma in this localization and to review the
      literature. METHODS: Retrospective study. Between 1988 and 2002, 9 patients (8
      female, mean age 50 years) underwent surgery via the retrolabyrinthine approach
      for resection of meningiomas inserted around the lateral sinus between the
      transverse and sigmoid parts. RESULTS: Resection was total (8 Simpson I and 1
      Simpson II) in all patients. In the early postoperative course, one patient was
      treated for meningitidis with an LCR leak and one patient present a temporary
      paresis of the vagus nerve. Mean follow-up was 5 years (6 months-10 years). All
      patients continued their pre-treatment occupation after surgery. No recurrence
      was observed. CONCLUSION: Two approaches can be used for resection of meningiomas
      in this localization. The retrosigmoid approach is a common neurosurgical
      approach exposure of the cerobellopontine angle. It is practised by most
      neurosurgeons. Via this approach, the cerebellar lobe must be pushed back so the
      arteries feeding the tumor are in the operative field at the end of the
      procedure. For numerous authors the operative field is too narrow. On the other
      hand, the retrolabyrinthine approach described in 1972 by Hitselberger and Pulec
      allows exposure of feeding arteries during the first steps of operation, an
      easier resection of meningioma insertion and better control of the lateral sinus.
      This approach can be enlarged to the retrosigmoid or the subtemporal anatomic
      region.

PMID- 17185949
TI  - [Obstructif sleep apnea-hypopnea syndrome: evolution of an old concept].
AB  - This review summarizes the well-known clinical features of the obstructive sleep
      apnea-hypopnea syndrome (OSAHS) and emphasizes new research on this syndrome.
      Though described in the seventies, the prevalence OSAHS is known mainly in the
      US. A dramatic increasing in prevalence has been related to the increase
      prevalence of obesity, raising a substantial public health problem. Discussion
      continues on the proper definition of the syndrome and degrees of severity.
      Multiple factors are involved in the pathogenesis of sleep apnea: anatomic
      abnormalities, mechanical factors, nervous alterations, muscular imbalance
      between pharyngeal constrictor and dilator muscles or part of a metabolic
      syndrome? Indeed, obstructive sleep apnea with and without obesity is
      increasingly implicated in the initiation and progression of metabolic disorders
      and of cardiovascular diseases (hypertension, cardiac ischemia and probably
      congestive heart failure, cardiac arrhythmias and strokes). An extended
      literature reports the neural, humoral, thrombotic, metabolic and inflammatory
      mechanisms linking OSAHS to endocrinology and cardiovascular diseases. Daytime
      sleepiness, cognitive, memory and performance deficits with their risks are also
      stressed. These consequences require treating this syndrome as soon as possible.
      Multiple interventions (medical, mechanical-nasal positive airway pressure or
      oral appliances, and sometimes surgical management) can be used but nasal
      continuous positive airway pressure is the "gold standard" treatment in severe
      OSAHS. More often multiple interventions are appropriate in a given patient.
      Finally, there is growing evidence that genetic factors influence the expression
      of OSAHS. Numerous genetic studies have investigated the etiology of OSAHS with
      the goal of improving our understanding of its pathogenesis.

PMID- 17185950
TI  - [History of neurosurgery at Rennes].

PMID- 17185952
TI  - [What is the real impact of the impact factor?].

PMID- 17185953
TI  - [Management of ovarian cysts].
AB  - Ovarian cysts occur frequently in women of reproductive age. These are usually
      functional cysts which resolve spontaneously and whose evolution can be followed
      with ultrasound. Non-functional cysts have diverse histologic origins. The most
      common are serous and mucinous cystadenomas which arise from the epithelial wall
      of the ovary, endometriomas which arise in the setting of pelvic endometriosis,
      and dermoid cysts which arise from the germinal cells of the ovary. Endovaginal
      ultrasound with Doppler enhancement is the best imaging technique to establish
      the nature of cysts and to distinguish cysts suspicious for malignancy which
      require more invasive investigation. Pelvic laparoscopy is the surgical approach
      of choice for the treatment of non-functional benign ovarian cysts. Conservative
      treatment to shell out the cyst and preserve functional ovarian tissue should be
      reserved for women desirous of future pregnancies. The risk of ovarian cancer
      remains a major preoccupation of the surgeon. Where malignancy is suspected,
      laparoscopy is contraindicated and a median laparotomy is appropriate for radical
      extirpative surgery. This article describes the diagnostic techniques which allow
      a laparoscopic approach to presumably benign cysts and discusses surgical
      techniques specifically adapted to their different histologic nature of ovarian
      cysts.

PMID- 17185954
TI  - [Carcinoma of the transverse colon].
AB  - Carcinoma of the transverse colon accounts for 10% of all colorectal cancer.
      Diagnosis is often delayed and complicated forms (perforation, fistulization,
      obstruction) occur in 30-50% of cases. The progression of symptoms is often
      insidious and tumors may be voluminous by the time of diagnosis. Right sided
      tumors are typically bulky and late-stage; perforation may lead to abdominal wall
      or retroperitoneal abscess. Tumor can also extend or fistulize into adjacent
      organs. Distal transverse cancers may be small annular lesions which are prone to
      obstruction. Cancers present as T4 lesions in 20-40% of cases. Abdominal CT is
      the best test to evaluate the loco-regional extension of advanced tumors. Their
      central location and advanced stage at presentation results in an extensive
      differential diagnosis. This central location also poses difficult surgical
      choices for lymph node dissection, extent of resection, and re-establishment of
      intestinal continuity. Surgical series which focus on transverse colon cancer
      date from the 1970-80's; they show curative resections in only 50% with
      morbidity/mortality of 20% and a global five year survival of less than 35%; they
      were considered to have a particularly poor prognosis.

PMID- 17185955
TI  - [Percutaneous drainage of abdomino-pelvic collections. Indications, techniques,
      and results].
AB  - Extra-parenchymal collections in the abdomen and pelvis are a not infrequent
      occurrence in gastrointestinal pathologies. Twenty years of experience have
      proved percutaneous drainage to be a safe and effective therapeutic modality.
      Several studies have demonstrated the efficacy of radio-guided percutaneous
      drainage which can serve as a substitute for open surgical drainage in 70% of
      cases. This therapeutic modality should be considered for every case of abdomino
      pelvic collection.

PMID- 17185957
TI  - [Esophagogastrectomy with stripping of the esophagus for caustic lesions].

PMID- 17185956
TI  - [Martius flap: bulbocavernous interposition flap].

PMID- 17185958
TI  - [Laparoscopic cecal resection].

PMID- 17185959
TI  - [Choledochal cyst associated with dilatation of the cystic duct].

PMID- 17185961
TI  - [Paleosurgery or the birth of the surgical art].

PMID- 17185960
TI  - [Benign pre-sacral teratoma and vestigial retrorectal cysts in the adult].
AB  - Benign mature presacral teratomas or dermoid cysts occur rarely in the adult; the
      incidence is estimated at less than 1/40,000. They are considered to be
      retrorectal vestigial growths from embryonal rests; they are usually asymptomatic
      and discovered by chance. However, since they have a 20-30% risk of secondary
      infection and a 1-12.5% risk of malignant degeneration, they should undergo
      complete surgical resection. We present a case of presacral dermoid cyst in a
      young male and summarize the diagnostic and therapeutic management.

PMID- 17185962
TI  - [Leiomyosarcoma of the infra-renal vena cava].

PMID- 17185963
TI  - [A penile metastasis as the first manifestation of colon cancer].

PMID- 17185964
TI  - [Cecal volvulus].

PMID- 17185965
TI  - [What role can the hepato-gastroenterologist play in gastro-intestinal
      oncology?].

PMID- 17185966
TI  - Is there any relationship between pernicious anemia and iron deficiency?
AB  - INTRODUCTION: Previous studies have suggested that iron deficiency could be due
      to atrophic gastritis of the body/fundus. The aim of this study was to determine
      the prevalence of iron deficiency among patients with pernicious anemia and
      associated factors. PATIENTS AND METHODS: All patients with pernicious anemia
      diagnosed at our institution between January 1990 and February 2005 were
      included. Inclusion criteria were: 1- histological diagnosis of atrophic fundic
      gastritis and 2- criteria of gastric autoimmune involvement. Histology of gastric
      biopsies was performed in a blinded manner. Iron deficiency was defined as serum
      ferritin level<15 microg/L in women and<40 microg/L in men. RESULTS: Ninety-five
      patients (69 women), mean age 60 years (range: 23-90) were included. Twenty
      patients (21.1%) had normal blood cell counts; 12 patients (12.6%) had
      microcytosis with or without anemia and 53 patients (55.8%) macrocytosis with or
      without anemia. Serum ferritin levels were measured in 58 patients, 16 (27.6%) of
      whom, all women, had iron deficiency. They were significantly younger (39.2
      years) than patients without iron deficiency (61.6 years, P<0.0001). Serum
      gastrin levels did not differ between the groups with and without iron
      deficiency. A significantly more severe inflammatory infiltrate of the fundus and
      endocrine cell hyperplasia was observed in iron deficiency patients. Multivariate
      analysis showed that iron deficiency was linked to female gender and age<50
      years. CONCLUSION: Iron deficiency and microcytic anemia are not rare in patients
      with pernicious anemia and should not rule out the diagnosis. Iron deficiency
      does not appear to be related to the degree of atrophic fundic gastritis but is
      linked to female gender and young age, suggesting menstrual blood loss could play
      a role. Whether decreased iron absorption due to reduced acid secretion favors
      the expression of gynecological iron loss cannot be ascertained.

PMID- 17185967
TI  - Who is implicated in the care of digestive cancers? A population-based study over
      a 25-year period.
AB  - OBJECTIVES: The aim of this study was to study health care delivery patterns
      during the initial phase of the management of digestive cancers in the Cote-d'Or
      area between 1976 and 2000 and to learn about the impact of patient- and disease
      related features on trends in care patterns. METHOD: Health care patterns were
      divided into 3 categories depending on whether care was delivered by public or
      private health care providers or a combination of the two. A polytomous logistic
      regression model was used to search for factors associated with the choice of
      health care delivery. RESULTS: In the Cote-d'Or area, 12 055 new digestive cancer
      cases were diagnosed between January 1, 1976 and December 31, 2000, including 6
      304 colorectal cancers. Public care structures managed 39% of patients, private
      care structures 42% and both (combined pattern) 19%. Women, young patients and
      patients with early-stage cancer were more often managed by private than by
      public facilities. Private health care institutions exclusively managed more
      colorectal cancers than public institutions (49.7% vs 34.2%) and fewer liver
      cancers (23.3% vs 62.8%) or pancreatic cancers (34.8% vs 47.5%). There was an
      increasing trend toward management by private instead of public institutions over
      the period. The proportion of exclusive private care rose from 35.0% (1976-1980)
      to 44.6% (1996-2000). Cancers diagnosed following symptoms concerned 85% of cases
      and were more often managed in private clinics. Cancers diagnosed in an emergency
      setting were more often managed in public institutions (48.3% vs 42.0%).
      CONCLUSION: This study highlights the disparity of the characteristics of
      patients with digestive cancers depending on the type of institution delivering
      health care, with a trend toward an increasing role for private health care
      centres. The present findings suggest that data collected from a specific care
      pattern cannot be extrapolated to the general population.

PMID- 17185968
TI  - Ethanol versus radiofrequency ablation for the treatment of small hepatocellular
      carcinoma in patients with cirrhosis: a retrospective study of efficacy and cost.
AB  - OBJECTIVE: To compare cost effectiveness of radio-frequency (RF) ablation versus
      percutaneous ethanol (Pe) ablation for treatment of small hepatocellular
      carcinoma. METHODS: 57 patients with 72 hepatocellular carcinomas (HCC) treated
      with ethanol ablation were retrospectively compared with 60 new patients who had
      72 HCC treated with RF ablation. All patients had Child-Pugh A cirrhosis and HCC
      less than 3.5 cm in diameter. Therapeutic efficacy was evaluated with tri-phase
      spiral computed tomography. Cost of hospital stay, supplies and follow-up
      including complications were calculated. Survival was estimated by Kaplan-Meier
      method and prognostic value of treatment methods by Log Rank test and
      multivariate Cox proportional hazard model. RESULTS: The two groups had similar
      baseline characteristics. The rate of severe complications associated with RF was
      15% (9/60) vs 6,9% (9/60) with Pe (P=0,11) The two-year overall survival, disease
      free survival and local tumor free survival in the ethanol and radiofrequency
      groups were 70.8% vs. 91.2% (Odd Ratio=3.7, P=0.006), 48.6% vs. 71.1% (Odd
      Ratio=2.2, P=0.01), and 68.5% vs. 80.7%, (Odd Ratio=1.9; P=0.09), respectively.
      The treatment method was the sole significant factor related to overall and tumor
      free survival. Costs per patient of ethanol and radiofrequency treatments were
      1534 euro and 1196 euro, respectively. CONCLUSION: This retrospective study
      suggests that RF is the most cost effective strategy, with higher 2-year disease
      free survival rate.

PMID- 17185969
TI  - Nosocomial transmission of hepatitis B virus associated with endomyocardial
      biopsy.
AB  - OBJECTIVES: A high prevalence of chronic hepatitis B has been previously reported
      in heart transplant recipients in our center. Nosocomial transmission of
      hepatitis B has been therefore suggested. The aim of the present study was to
      investigate an outbreak of hepatitis B infection in heart transplant recipients
      and to to look for nosocomial acquisition of hepatitis B in these patients.
      METHODS: In a retrospective case-control study, review of transvenous
      endomyocardial biopsy (TEB) procedure, line probe assay and DNA sequencing for
      characterization of the outbreak isolate genotypes were performed in order to
      assess the possible risk of nosocomial transmission of hepatitis B in the setting
      of heart transplantation. Case was defined as a patient negative for HBsAg before
      heart transplantation and positive after. Controls were matched with cases by
      date of transplantation and time-interval of HBV infection occurrence in the
      cases patients. RESULTS: Transmission of HBV was associated with the number of
      HBsAg positive patients undergoing TEB the same day and in the same ward
      (OR=1.17, per additional encounter; 95%CI=1.01-1.37, P=0.02) and with the total
      number of TEB undergone after a HBsAg positive patient (OR=1.43 for additional
      encounter, 95%CI=0.97-2.1, P=0.056) but not with the number of biopsies. The
      virological study identified eight different strains. No common devices nor
      gloves, drapes, or medical solution were shared among patients during TEB. One
      staff member, but no surgeon, was HBsAg positive. No further case occurred after
      implementation of control measures. CONCLUSIONS: Patient-to-patient transmission
      during TEB sessions was demonstrated by the virological and the case-control
      studies. This transmission occurred without evidence of blood contact through
      vials or devices. There is strong evidence that this transmission may be due to
      the spread of infective blood droplets on the environmental surfaces and the
      material during the TEB procedure.

PMID- 17185970
TI  - [Hepatitis C and liver transplantation: fibrosis progression and treatment. Or
      how to improve management].
AB  - Hepatitis C virus-related end-stage liver disease, alone or in combination with
      alcohol, has become the leading indication for liver transplantation in most
      transplant programs accounting for approximately half of transplants performed in
      European centers. Hepatitis C virus infection recurs virtually in every post
      transplant patient. The natural history of hepatitis C after liver
      transplantation is variable. Progression of chronic hepatitis C virus is more
      aggressive after liver transplantation with a cumulative probability of
      developing graft cirrhosis estimated to reach 30% at 5 years. Approximately 10%
      of the patients with recurrent disease will die or require re-transplantation
      within 5 years post-transplantation. Several factors, including those related to
      the virus, the host, the environment and the donor, are probably implicated in
      the outcome. The immune status represents the main significant variable in
      influencing disease severity in hepatitis C virus-infected patients; with higher
      HCV viral load and the significant association described between the degree of
      immunosuppression and disease severity. Interventions to prevent, improve, or
      halt the recurrence of hepatitis C virus infection have been evaluated by
      multiple small studies worldwide with similar overall rates of virological
      clearance of approximately 9-30%. Current consensus recommends combination
      therapy with pegylated interferon and ribavirin for those patients with
      histological recurrence of hepatitis C virus infection and fibrosis. Therapy is
      adjusted to tolerance and rescued with granulocyte colony-stimulating factor and
      erythropoietin for bone marrow suppression. In this article we present a
      comprehensive review of post-transplant hepatitis C virus infection; in
      particular fibrosis progression and the major challenges according to treatment.

PMID- 17185971
TI  - [Intraperitoneal hyperthermic chemotherapy in the management of recurrent
      peritoneal carcinomatosis. Preliminary results in 5 patients].
AB  - Peritoneal carcinomatosis has been treated by extensive cytoreduction surgery and
      hyperthermic intraperitoneal chemotherapy (HIPEC). We report here our experience
      of 5 patients treated twice or three times by recurrent procedure of HIPEC and
      cytoreduction. The mortality rate was 0% and morbidity one 30%. Three patients
      have died at 6, 10, 18 months respectively after the second cytoreduction surgery
      and HIPEC, and two patients are still alive at 40 and 67 months. Our results
      might suggest that recurrent peritoneal carcinomatosis after cytoreduction and
      HIPEC, could be usefully treated by another cytoreduction and HIPEC procedure in
      a curative approach superior to more conventional treatments.

PMID- 17185972
TI  - [Pancreatic intraductal tubular carcinoma: a sub-group of intraductal papillary
      mucinous tumors or a distinct entity? A case report and review of the
      literature].
AB  - We report the case of a 67-year-old man presenting with an isolated 3 cm mass of
      the pancreatic tail revealed by weight loss. Distal pancreatectomy and
      splenectomy were performed. Microscopically, the tumor filled the main pancreatic
      duct, extending into the smaller ducts and was associated with a minor
      adenocarcinomatous invasive component. The intraductal tumor showed a cribriform
      pattern, atypical cells without mucus and a MUC1+, MUC2-, MUC5AC- phenotype, all
      characteristics of intraductal tubular carcinoma, a new entity described by
      Japanese authors. The differential diagnosis and its relationship with
      intraductal papillary-mucinous tumors are discussed.

PMID- 17185973
TI  - [An exceptional and misleading case of choledochal cyst].
AB  - The authors report a case of choledocal cyst extended to left and right hepatic
      ducts. An heterogeneous intracystic fluid, partial calcification of cystic wall,
      a slight positivity of echinoccosis serology in a patient from a highly endemic
      country erroneously led to diagnosis of hydatid cyst invading the left hepatic
      duct. The diagnosis of choledocal cyst was done on the resection specimen after
      left hepatectomy. A small patch of cyst wall with terminations of both right
      sectorial hepatic ducts was used for cysto-jejunal Roux-en-Y loop anastomosis.
      Peculiarities of this type of choledocal cyst are discussed.

PMID- 17185974
TI  - [Portal hypertension due to Castelman's disease in an adolescent].

PMID- 17185975
TI  - How to manage splenic rupture during major liver resection?
AB  - Spontaneous splenic rupture is a rare but life threatening complication of major
      liver resection with only five reported cases during major liver resection under
      hepatic vascular occlusion. We report two cases of splenic rupture during liver
      resection including the first case during portal triad clamping. In both
      patients, the hemorrhage was stopped by removing the vascular clamp. A
      splenectomy was performed in both patients and liver resection was completed
      under vascular clamping without complications. Although very rare, physicians
      should be aware of the possibility of splenic rupture during liver resection
      because instead of increasing vascular occlusion, clamp removal usually stops the
      hemorrhage.

PMID- 17185976
TI  - Severe sinusoidal lesions: a serious and overlooked complication of oxaliplatin
      containing chemotherapy?
AB  - The main toxicity of Oxaliplatin, a major drug in the treatment of metastatic
      colorectal carcinoma, is neurologic. Severe sinusoidal lesions of the liver have
      been recently described in patients receiving pre-operative (neoadjuvant)
      oxaliplatin-containing chemotherapy, but their clinical relevance is unknown.
      Four patients with metastatic colon cancer receiving oxaliplatin, 5 fluorouracil
      and elvorin, developped a progressive increase in gammaglutamyl transpeptidase
      and alkaline phosphatase, contrasting with tumour regression established by CT
      scan and decrease in serum carcinoembryonic antigen concentrations. Histological
      examination of liver biopsies showed sinusoidal dilatation in all cases, with
      perisinusoidal fibrosis and centrilobular vein lesions in 3, peliosis in 1 (in a
      patient receiving oxaliplatine by intraarterial hepatic route), and nodular
      regenerative hyperplasia in 1. The patient with peliosis developped ascites, and
      died from hepatic failure, despite withdrawal of the drug. The patient with
      nodular regenerative hyperplasia developped jaundice, ascites and severe
      infection following a right hepatectomy. In the three surviving patients, liver
      function tests improved after the withdrawal of oxaliplatin, and, in one,
      deteriorated again after reintroduction of the drug. The prevalence of liver
      sinusoid lesions induced by oxaliplatin-containing chemotherapeutic regimens is
      probably underestimated. Careful monitoring of gamma-glutamyl transpeptidase and
      alkaline phosphatase is mandatory in treated patients, especially in those
      receiving adjuvant therapy, in whom significant sequelae could occur despite
      initially asymptomatic lesions.

PMID- 17185977
TI  - [Hepatic tuberculosis: case report of pseudotumoral form].
AB  - Inflammatory pseudo-tumors of the liver are rare and difficult to diagnose,
      mimicking malignant tumors. We report a patient, 42 year old with hepatic pseudo
      tumor who was suspected to have pseudotumoral hepatic tuberculosis without
      immunodepression and treated by major hepatic surgery because no sure diagnosis.
      Therapeutic approach of hepatic inflammatory pseudotumors is often medical and
      surgical and may need major hepatic surgery in case of sure etiologic diagnosis.

PMID- 17185978
TI  - [Duodenal stenosis revealing duodenal hematoma in the course of alcoholic acute
      pancreatitis].

PMID- 17185979
TI  - [Adult rheumatoid purpura revealed by intestinal ischemic syndrome].

PMID- 17185980
TI  - [Rapunzel syndrome associated with small bowel intussusception, acute
      pancreatitis and bile duct dilatation].

PMID- 17185982
TI  - Isolation of murine hair-inducing cells using the cell surface marker prominin
      1/CD133.
AB  - Hair is a mini-organ in which dermal papilla (DP) cells play important roles in
      hair follicle morphogenesis and formation via interactions with epithelial cells.
      DP cells have previously been difficult to analyze because of the lack of a
      specific surface marker. We have demonstrated that prominin-1/CD133 (CD133) is a
      useful marker for murine DP cells. DP cells express CD133 during the early anagen
      stage (active growth phase) not only during hair morphogenesis, but also during
      the growth phase of hairs after birth. Gene expression and flow cytometric
      analysis revealed that CD133-positive (+) cells in the skin possess the
      characteristics of DP cells. The CD133(+) cells isolated from embryonic or adult
      skin-induced new hair follicles in vivo when they were transplanted into nude
      mice mixed with embryonic epithelial cells, but CD133-negative (-) cells could
      not. We propose that the CD133 is a novel surface marker useful for collecting DP
      cells in the anagen stage and for analyzing the function of DP.

PMID- 17185981
TI  - Human epidermal keratinocytes accumulate superoxide due to low activity of Mn
      SOD, leading to mitochondrial functional impairment.
AB  - The energy metabolism of the epidermis has been the subject of controversy; thus
      we characterized the mitochondrial phenotype of human primary keratinocytes and
      fibroblasts, in cell culture and in human skin sections. We found that
      keratinocytes respire as much as fibroblasts, however, maximal activities of the
      respiratory chain (RC) complexes were 2- to 5-fold lower, whereas expression
      levels of RC proteins were similar. Maximal activities of aconitase and
      isocitrate dehydrogenase, two mitochondrial enzymes especially vulnerable to
      superoxide, were lower than in fibroblasts. Indeed, superoxide anion levels were
      much higher in keratinocytes, and keratinocytes displayed higher lipid
      peroxidation levels and a lower reduced glutathione/oxidized glutathione ratio,
      indicating enhanced oxidative stress. Although superoxide dismutase activity and
      especially expression of the mitochondrial superoxide dismutase, Mn-SOD, were
      drastically lower in keratinocytes, explaining the high superoxide levels,
      glutathione peroxidase activity and protein were almost undetectable in
      fibroblasts. Catalase activity and hydrogen peroxide levels were similar. In
      summary, we could show that keratinocytes actively use the mitochondrial RC not
      only for adenosine 5' triphosphate synthesis but also for the accumulation of
      superoxide anions, even at the expense of mitochondrial functional capacity,
      indicating that superoxide-driven mitochondrial impairment might be a
      prerequisite for keratinocyte differentiation.

PMID- 17185983
TI  - Deletion of mu- and kappa-opioid receptors in mice changes epidermal hypertrophy,
      density of peripheral nerve endings, and itch behavior.
AB  - The mu- (MOR) and kappa- (KOR) opioid receptors have been implicated in the
      regulation of homeostasis of non-neuronal cells, such as keratinocytes, and
      sensations like pain and chronic pruritus. Therefore, we have studied the
      phenotype of skin after deletion of MOR and KOR. In addition, we applied a dry
      skin model in these knockout mice and compared the different mice before and
      after induction of the dermatitis in terms of epidermal thickness, epidermal
      peripheral nerve ending distribution, dermal inflammatory infiltrate (mast cells,
      CD4 positive lymphocytes), and scratching behavior. MOR knockout mice reveal as
      phenotype a significantly thinner epidermis and a higher density of epidermal
      fiber staining by protein gene product 9.5 than the wild-type counterparts.
      Epidermal hypertrophy, induced by the dry skin dermatitis, was significantly less
      developed in MOR knockout than in wild-type mice. Neither mast cells nor CD4 T(h)
      lymphocytes are involved in the changes of epidermal nerve endings and epidermal
      homeostasis. Finally, behavior experiments revealed that MOR and KOR knockout
      mice scratch less after induction of dry skin dermatitis than wild-type mice.
      These results indicate that MOR and KOR are important in skin homeostasis,
      epidermal nerve fiber regulation, and pathophysiology of itching.

PMID- 17185984
TI  - A human mAb specific to oncofetal fibronectin selectively targets chronic skin
      inflammation in vivo.
AB  - The antibody-based targeted delivery of bioactive agents to sites of angiogenesis
      is an attractive therapeutic strategy for cancer treatment, but is largely
      unexplored for chronic inflammatory diseases. In this article, we show that the
      extra domain B (EDB) domain of fibronectin, a marker of angiogenesis, is
      expressed in psoriatic lesions, and that the anti-EDB human antibody L19 can
      selectively localize to chronically inflamed skin in vivo. The L19-based delivery
      of the cytokines IL10 and IL12 did not improve or worsen inflammation in a mouse
      model of chronic skin inflammation, which overexpressed vascular endothelial
      growth factor under the control of the keratin-14 promoter. By contrast, the L19
      based targeted delivery of the proinflammatory cytokine IL2 or of the
      photosensitizer Sn(IV) chlorin e6 resulted in an increased swelling and reddening
      of inflamed skin. These results indicate that antibodies specific to components
      of the modified extracellular matrix can selectively accumulate at chronically
      inflamed sites in vivo. This observation now stimulates the search for bioactive
      molecules which can be fused to antibodies and which may confer a therapeutic
      benefit as a result of their preferential accumulation in psoriatic lesions and
      other sites of inflammation.

PMID- 17185986
TI  - Clinical pharmacology: the science of therapeutics.

PMID- 17185989
TI  - The electronic prescription conundrum: why "e-Rx" isn't so "e-Z".

PMID- 17185990
TI  - The value and future of clinical pharmacology.

PMID- 17185991
TI  - Clinical pharmacology or translational medicine and therapeutics: reinvent or
      rebrand and expand?

PMID- 17185993
TI  - Nontraditional approaches to first-in-human studies to increase efficiency of
      drug development: will microdose studies make a significant impact?
AB  - Much has been written recently about low productivity in the pharmaceutical
      industry and the high cost of drug development. Over a 10-year period ending in
      2000, only approximately 11% of compounds tested in humans across 10 large
      pharmaceutical companies were eventually approved for marketing in the United
      States and/or Europe. Attrition was highest during phase II (62%) but still
      significant in phase III (45%) and at the time of registration (23%). Clearly,
      given the high cost and time required for clinical development, these late-stage
      failures are unsustainable.

PMID- 17185992
TI  - The PharmGKB: integration, aggregation, and annotation of pharmacogenomic data
      and knowledge.
AB  - The Pharmacogenetics and Pharmacogenomics Knowledge Base, PharmGKB
      (http://www.pharmgkb.org), curates pharmacogenetic and pharmacogenomic
      information to generate knowledge concerning the relationships among genes,
      drugs, and diseases, and the effects of gene variation on these relationships.
      PharmGKB curators collect information on genotype-phenotype relationships both
      from the literature and from the deposition of primary research data into our
      database. Their goal is to catalyze pharmacogenetic and pharmacogenomic research.

PMID- 17185994
TI  - Gene mutations, atrial fibrillation, and the elusive cigar.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia. The term lone AF
      describes nonsyndromic atrial fibrillation that occurs in the absence of
      underlying structural heart disease or predisposing clinical conditions. A
      hereditable component leading to conduction abnormalities in AF has long been
      suspected, and epidemiological evidence of elevated risk for AF among first
      degree relatives of probands was recently documented. The first AF-associated
      molecular defect was found in an affected Chinese family; initial studies
      narrowed the chromosomal location by linkage analysis, and Yihan Chen et al.
      found a specific gain-of-function mutation in KCNQ1, the gene for the alpha
      subunit of potassium channels.

PMID- 17185995
TI  - PharmGED: pharmacogenetic effect database.

PMID- 17185996
TI  - In silico drug discovery: solving the "target-rich and lead-poor" imbalance using
      the genome-to-drug-lead paradigm.
AB  - Advances in genomics, proteomics, and structural genomics have identified a large
      number of protein targets. Virtual screening has gained popularity in identifying
      drug leads by computationally screening large numbers of chemicals against
      experimentally determined protein targets. In that context, there continues to be
      a "target-rich and lead-poor" imbalance, reflecting an insufficiency of chemists
      pursuing drug discovery in academia, the challenge of engaging more chemists in
      this area of research, and a paucity of available protein target structures. This
      imbalance in manpower and structural information can be ameliorated, in part, by
      adapting a "genome-to-drug-lead" approach, in which chemicals can be virtually
      screened against computer-predicted protein targets, within the context of the US
      National Science Foundation's petascale computing initiative. This approach
      offers a solution to reduce manpower requirements for more chemists to
      experimentally search for drug leads, which represent one of the greatest
      limitations to drug discovery and better exploits the extensive availability of
      drug targets at the gene level, ultimately improving the success of moving
      discoveries from the laboratory to the patient.

PMID- 17185998
TI  - Irinotecan-induced diarrhea: functional significance of the polymorphic ABCC2
      transporter protein.
AB  - Interindividual pharmacokinetic variability of the anticancer agent irinotecan is
      high. Life-threatening diarrhea is observed in up to 25% of patients receiving
      irinotecan and has been related with irinotecan pharmacokinetics and UGT1A1
      genotype status. Here, we explore the association of ABCC2 (MRP2) polymorphisms
      and haplotypes with irinotecan disposition and diarrhea. A cohort of 167
      Caucasian cancer patients who were previously assessed for irinotecan
      pharmacokinetics (90-min infusion given every 21 days), toxicity, and UGT1A1*28
      genotype were genotyped for polymorphisms in ABCC2 using Pyrosequencing. Fifteen
      ABCC2 haplotypes were identified in the studied patients. The haplotype ABCC2*2
      was associated with lower irinotecan clearance (28.3 versus 31.6 l/h; P=0.020).
      In patients who did not carry a UGT1A1*28 allele, a significant reduction of
      severe diarrhea was noted in patients with the ABCC2*2 haplotype (10 versus 44%;
      odds ratio, 0.15; 95% confidence interval, 0.04-0.61; P=0.005). This effect was
      not observed in patients with at least one UGT1A1*28 allele (32 versus 20%; odds
      ratio, 1.87; 95% confidence interval, 0.49-7.05; P=0.354). This study suggests
      that the presence of the ABCC2*2 haplotype is associated with less irinotecan
      related diarrhea, maybe as a consequence of reduced hepatobiliary secretion of
      irinotecan. As the association was seen in patients not genetically predisposed
      at risk for diarrhea due to UGT1A1*28, confirmatory studies of the relationships
      of ABCC2 genotypes and irinotecan disposition and toxicity are warranted.

PMID- 17185997
TI  - A common polymorphism in SCN5A is associated with lone atrial fibrillation.
AB  - The cardiac sodium channel (SCN5A) is a target for the treatment of arrhythmias.
      We hypothesized that vulnerability to atrial fibrillation (AF) could be caused by
      genetic variation in SCN5A. We recruited 157 patients with early-onset AF who
      lacked traditional risk factors, and 314 matched controls. SCN5A was subject to
      targeted genotyping of a common loss-of-function H558R polymorphism and
      comprehensive mutation scanning. Genotype frequencies in the AF cohort vs
      controls were as follows: HH, 50 vs 63%; HR, 40 vs 33%; and RR, 10 vs 4%
      (P=0.008). Additional coding sequence mutations were ruled out. The R558 allele
      was more common in patients than in controls (30 vs 21%, P=0.002), conferring an
      odds ratios for AF of 1.6 (95% confidence interval 1.2-2.2). The SCN5A R558
      allele, present in one-third of the population, thus constitutes a risk factor
      for lone AF and may increase susceptibility to sodium channel blocker-induced
      proarrhythmia.

PMID- 17185999
TI  - Mechanism-based PK/PD modeling of the respiratory depressant effect of
      buprenorphine and fentanyl in healthy volunteers.
AB  - The objective of this study was to characterize the
      pharmacokinetic/pharmacodynamic (PK/PD) relationship of buprenorphine and
      fentanyl for the respiratory depressant effect in healthy volunteers. Data on the
      time course of the ventilatory response at a fixed P(ET)CO(2) of 50 mm Hg and
      P(ET)O(2) of 110 mm Hg following intravenous administration of buprenorphine and
      fentanyl were obtained from two phase I studies (50 volunteers received
      buprenorphine: 0.05-0.6 mg/70 kg and 24 volunteers received fentanyl: 0.075-0.5
      mg/70 kg). The PK/PD correlations were analyzed using nonlinear mixed effects
      modeling. A two- and three-compartment pharmacokinetic model characterized the
      time course of fentanyl and buprenorphine concentration, respectively. Three
      structurally different PK/PD models were evaluated for their appropriateness to
      describe the time course of respiratory depression: (1) a biophase distribution
      model with a fractional sigmoid E(max) pharmacodynamic model, (2) a receptor
      association/dissociation model with a linear transduction function, and (3) a
      combined biophase distribution-receptor association/dissociation model with a
      linear transduction function. The results show that for fentanyl hysteresis is
      entirely determined by the biophase distribution kinetics, whereas for
      buprenorphine hysteresis is caused by a combination of biophase distribution
      kinetics and receptor association/dissociation kinetics. The half-time values of
      biophase equilibration (t(1/2, k(eo))) were 16.4 and 75.3 min for fentanyl and
      buprenorphine, respectively. In addition, for buprenorphine, the value of k(on)
      was 0.246 ml/ng/min and the value of k(off) was 0.0102 min(-1). The concentration
      effect relationship of buprenorphine was characterized by a ceiling effect at
      higher concentrations (intrinsic activity alpha=0.56, 95% confidence interval
      (CI): 0.50-0.62), whereas fentanyl displayed full respiratory depressant effect
      (alpha=0.91, 95% CI: 0.19-1.62).

PMID- 17186000
TI  - The partial 5-hydroxytryptamine1A receptor agonist buspirone does not antagonize
      morphine-induced respiratory depression in humans.
AB  - Based on experiments in rats, serotonin receptor 5-hydroxytryptamine (5-HT)(1A)
      agonists have been proposed as a potential therapeutic strategy for the selective
      treatment of opioid-induced respiratory depression. We investigated the clinical
      applicability of this principle in healthy volunteers. Twelve subjects received
      0.43 mg/kg morphine (30 mg for 70 kg body weight) administered intravenously
      (i.v.) over approximately 2 h. At the start of the morphine infusion, they
      received in a randomized, double-blind cross-over design 60 mg p.o. buspirone or
      placebo. Respiratory depression (hypercapnic challenge) and pain (electrical
      stimuli: 5 Hz sinus 0-20 mA; chemical stimuli: 200 ms gaseous CO(2) pulses
      applied to the nasal mucosa) were assessed at baseline, at the end of the
      morphine infusion, and a third time after antagonizing the opioid effects by i.v.
      administration of 2 mg naloxone. The linear relationship between the minute
      ventilation and the CO(2) concentration in the inspired air of 1.07+/-0.27 l/mm
      Hg CO(2) at baseline conditions became shallower (0.45+/-0.23 l/mm Hg CO(2))
      after morphine administration (P<0.001), indicating respiratory depression, which
      was significantly reversed by naloxone (0.95+/-0.43 l/mm Hg CO(2); P=0.001). Co
      administration of buspirone had no effect on morphine-induced respiratory
      depression (slope 0.45+/-0.23 l/mm Hg CO(2) under morphine plus placebo versus
      0.38+/-0.25 l/mm Hg CO(2) under morphine plus buspirone; P=0.7). Significant
      morphine-induced analgesia was observed in both pain models and was reversed by
      naloxone but unaffected by buspirone. Buspirone significantly increased the
      nausea induced by morphine (P=0.011). Oral co-administration of a high dose of
      the clinically available 5-HT(1A) agonist buspirone cannot be advised as a remedy
      for opioid-induced respiratory depression. This is indicated by its lack of anti
      respiratory depressive effects and by the buspirone-associated increase of
      morphine-induced nausea.

PMID- 17186001
TI  - Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects.
AB  - Limited data are available about the effect of steady-state lopinavir and
      ritonavir (LPV/r) on bupropion pharmacokinetics. As patients may benefit by using
      these two agents in combination, this study determined the extent and direction
      of this drug-drug interaction. Twelve healthy volunteers received a single 100 mg
      dose of sustained-release bupropion before and after 2 weeks of treatment with
      LPV/r 400 mg/100 mg twice daily. Pharmacokinetics profiles were determined on
      days 1 and 30 for bupropion and hydroxybupropion and days 29 and 30 for LPV/r.
      LPV/r administration significantly decreased bupropion maximum plasma
      concentration (C(max)) by 57% (90% confidence interval (CI), 38-76%; P<0.01) and
      area under the curve (AUC) infinity by 57% (90% CI, 32-83%; P<0.01).
      Hydroxybupropion C(max) and AUC infinity decreased by 31% (90% CI, 7-55%; P<0.01)
      and by 50% (90% CI, 34-65%; P<0.01), respectively. No significant changes in the
      pharmacokinetics of LPV/r were found following administration of a single dose of
      bupropion. Concurrent use of LPV/r and bupropion resulted in decreased exposure
      to bupropion and its active metabolite hydroxybupropion that may necessitate as
      much as a 100% dose increase of bupropion. A probable mechanism for this
      interaction is the concurrent induction of cytochrome P450 2B6 and UDP
      glucuronosyltransferase enzymes. LPV/r exposure is unaffected by a single dose of
      bupropion.

PMID- 17186002
TI  - Variants in the SLCO1B3 gene: interethnic distribution and association with
      paclitaxel pharmacokinetics.
AB  - To explore retrospectively the relationships between paclitaxel pharmacokinetics
      and three known, non-synonymous single-nucleotide polymorphisms (SNPs) in
      SLCO1B3, the gene encoding organic anion transporting polypeptide (OATP)1B3.
      Accumulation of [(3)H]paclitaxel was studied in Xenopus laevis oocytes injected
      with cRNA of Oatp1b2, OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and NTCP. The
      334T>G (Ser112Ala), 699G>A (Met233Ile), and 1564G>T (Gly522Cys) loci of SLCO1B3
      were screened in 475 individuals from five ethnic groups and 90 European
      Caucasian cancer patients treated with paclitaxel. Only OATP1B3 was capable of
      transporting paclitaxel to a significant extent (P=0.003). The 334T>G and 699G>A
      SNPs were less common in the African-American and Ghanaian populations
      (P<0.000001). Paclitaxel pharmacokinetics were not associated with the studied
      SNPs or haplotypes (P>0.3). The studied SNPs in SLCO1B3 appear to play a limited
      role in the disposition of paclitaxel, although their clinical significance in
      other ethnic populations remains to be investigated.

PMID- 17186003
TI  - Selective AT1 receptor antagonism enhances sympathetically mediated
      vasoconstriction in man.
AB  - The vasoconstrictive action of angiotensin II (AII) is partly, sympathetically
      mediated and angiotensin-converting enzyme (ACE) inhibitors appear to exert a
      sympatholytic effect. We examine the effect of an orally administered, selective
      AT(1) receptor antagonist (losartan 50 mg) on sympathetically mediated
      vasoconstriction in healthy volunteers in an observer blind crossover study.
      Seven healthy, normotensive volunteers (21-32 years), were studied on two
      occasions at the end of each 6-week treatment period (losartan or placebo).
      Forearm blood flow (FABF) (ml/dl forearm/min) was measured by venous occlusion
      plethysmography during the application of lower body negative pressure (LBNP) (
      20 cm H(2)O) and at the end of each incremental infusion of norepinephrine (60,
      120, and 240 pmol/min). Comparison of blood flow changes was by repeated measures
      analysis of variance; P<0.05 was taken as statistically significant. Losartan did
      not alter blood pressure compared to placebo. It did significantly enhance LBNP
      induced vasoconstriction in both the left arm compared to placebo (-36.6+/-3.4 vs
      -23.5+/-3.3%; P=0.017) and the right arm compared to placebo (-39.5+/-3.8 vs 
      21.0+/-3.6%; P=0.005). The FABF response to all doses of infused norepinephrine
      (60, 120, and 240 pmol/min) was also enhanced by losartan compared to placebo (
      35.0+/-2.7 vs -18.2+/-6.0%; -43.6+/-4.3 vs -28.6+/-5.8%, and -53.9+/-3.2 vs 
      42.5+/-6.8%; P=0.057, respectively. Losartan enhances locally mediated
      sympathetic vasoconstriction in the forearm circulation of man, probably through
      its effect on circulating AII concentrations and we postulate that the adrenergic
      sympathetic constrictor action of AII is not mediated by the AT(1) receptor or is
      surmountable at this receptor.

PMID- 17186004
TI  - A Bayesian population PK-PD model of ispinesib-induced myelosuppression.
AB  - The goal of the present analysis is to fit a Bayesian population pharmacokinetic
      pharmacodynomic (PK-PD) model to characterize the relationship between the
      concentration of ispinesib and changes in absolute neutrophil counts (ANC).
      Ispinesib, a kinesin spindle protein (KSP) inhibitor, blocks assembly of a
      functional mitotic spindle, leading to G2/M arrest. A first time in human, phase
      I open-label, non-randomized, dose-escalating study evaluated ispinesib at doses
      ranging from 1 to 21 mg/m(2). PK-PD data were collected from 45 patients with
      solid tumors. The pharmacokinetics of ispinesib were well characterized by a two
      compartment model. A semimechanistic model was fit to the ANC. The PK and PD data
      were successfully modelled simultaneously. This is the first presentation of
      simultaneously fitting a PK-PD model to ANC using Bayesian methods. Bayesian
      methods allow for the use of prior information for some system-related
      parameters. The model may be used to examine different schedules, doses, and
      infusion times.

PMID- 17186005
TI  - Frequency of CYP2D6*10 and *14 alleles and their influence on the metabolic
      activity of CYP2D6 in a healthy Chinese population.
AB  - To study the frequency of CYP2D6(*)10 and (*)14 alleles in a healthy Chinese
      population, and the influence of these two alleles on the metabolic activity of
      CYP2D6. CYP2D6(*)10 and (*)14 genotypes of 295 healthy Chinese subjects were
      determined using a tetra-primer method and allele-specific amplification. CYP2D6
      phenotypes of 131 subjects were determined using dextramethorphan as probe drug.
      There were 10 subjects with a (*)14 allele, including one homozygous for (*)14.
      The gene frequency of (*)10 and (*)14 alleles were 55.8 and 1.8%, respectively.
      The metabolic ratio (MR) of dextramethorphan in 131 subjects was 0.032+/-0.106.
      The MR of (*)1/(*)1, (*)1/(*)10, (*)10/(*)10, (*)1/(*)14, (*)10/(*)14, and
      (*)14/(*)14 groups were 0.007+/-0.012, 0.009+/-0.010, 0.042+/-0.029, 0.093, 0.11,
      and 1.186, respectively. The MR of subjects with (*)14 allele was higher than
      those of (*)1/(*)1, (*)1/(*)10, or (*)10/(*)10 groups (P<0.001). The CYP2D6(*)10
      and (*)14 alleles have substantial impact on the metabolic activity of CYP2D6,
      and the CYP2D6(*)14 allele may be the cause of the poor metabolizer phenotype in
      Chinese subjects.

PMID- 17186006
TI  - Aminoglycoside-induced translational read-through in disease: overcoming nonsense
      mutations by pharmacogenetic therapy.
AB  - A third of inherited diseases result from premature termination codon mutations.
      Aminoglycosides have emerged as vanguard pharmacogenetic agents in treating human
      genetic disorders due to their unique ability to suppress gene translation
      termination induced by nonsense mutations. In preclinical and pilot clinical
      studies, this therapeutic approach shows promise in phenotype correction by
      promoting otherwise defective protein synthesis. The challenge ahead is to
      maximize efficacy while preventing interaction with normal protein production and
      function.

PMID- 17186007
TI  - Biomarkers and surrogate end points for fit-for-purpose development and
      regulatory evaluation of new drugs.
AB  - A consistent framework for the acceptance and qualification of biomarkers for
      regulatory use is needed to facilitate innovative and efficient research and
      subsequent application of biomarkers in drug development. One key activity is
      biomarker qualification, a graded, "fit-for-purpose" evidentiary process linking
      a biomarker with biology and clinical end points. A biomarker consortium model
      will distribute cost and risk, and drive efficient execution of research and
      ultimately regulatory acceptance of biomarkers for specific indications.

PMID- 17186008
TI  - Cardiac repolarization and the safety of new drugs defined by
      electrocardiography.
AB  - A compelling assessment of both short- and long-term cardiac safety is
      increasingly emphasized before regulatory marketing approval. In that context,
      cardiac adverse effects that were otherwise unexpected become manifest when large
      numbers of subjects are treated after market approval, many of whom take multiple
      medications, have co-morbidities, and are subject to other conditions that were
      not represented in the original clinical trial population. Since 2005, dedicated,
      robust, and well-controlled electrocardiogram (ECG) trials are required, usually
      conducted in Phase II, to define the cardiac risk of a new therapy before large
      scale Phase III trials are conducted or marketing is approved.

PMID- 17186010
TI  - The ethical implications of stratifying by race in pharmacogenomics.
AB  - Many predict that pharmacogenomics is poised to deliver on the promises of the
      genomic revolution in ushering an era of personalized medicine. However,
      questions have emerged over whether the field will deliver a truly individualized
      medicine or if population-based therapies that build on conventional notions of
      racial biology will prevail. At the heart of this issue is the challenge of
      knowing which axes of stratification are appropriate in identifying population
      differences and to what extent is race and/or ethnicity an appropriate method of
      comparison in studies of genetic variation. These questions make plain that in
      addition to the development of technical tools to identify salient gene variants
      associated with drug response, serious consideration over how best to
      characterize populations in human genetic variation research must be given in
      order to realize the putative benefits of tailored therapeutics.

PMID- 17186009
TI  - Two cases of rapid onset Parkinson's syndrome following toxic ingestion of
      ethylene glycol and methanol.
AB  - Ethylene glycol and methanol are toxic alcohols commonly found in a variety of
      commercial products. We report two cases, one associated with ethylene glycol and
      one with methanol poisoning, which both led to acute hemorrhagic necrosis of the
      basal ganglia and resulted in acute Parkinson's syndrome. It is unlikely that
      oxalate crystal deposition is the only mechanism for such basal ganglia necrosis,
      because similar findings were seen following methanol intoxication. We discuss
      other possible mechanisms that may contribute towards this unusual neurotoxicity.
      Both of our patients survived their toxic ingestions, but then developed acute
      Parkinson's syndrome within 10 days of the ingestion. However, the patient who
      ingested methanol developed respiratory muscle stiffness/weakness, which
      responded poorly to anti-Parkinsonian drug therapy. Treatment with
      carbidopa/levodopa improved cogwheel rigidity and bradykinesia in both patients.
      We conclude that acute Parkinsonism is one of the lesser-recognized devastating
      complications of both ethylene glycol and methanol poisoning.

PMID- 17186011
TI  - Translational research: moving discovery to practice.
AB  - In the first week of October, I announced the launch of a national consortium
      that will transform how clinical and translational research is conducted;
      ultimately enabling researchers to provide new treatments more efficiently and
      quickly to patients. This new consortium, funded through Clinical and
      Translational Science Awards (CTSAs), begins with 12 academic health centers
      (AHCs) located throughout the nation. An additional 52 AHCs are receiving
      planning grants to help them prepare to apply for a CTSA.

PMID- 17186012
TI  - Drug development and the FDA's Critical Path Initiative.
AB  - Advances in biomedical research over recent decades have substantially raised
      expectations that the pharmaceutical industry will generate increasing numbers of
      safe and effective therapies. However, there are warning signs of serious
      limitations in the industry's ability to effectively translate biomedical
      research into marketed new therapies. Clinical pharmacologists should be aware of
      these signals and their potential impact. Here, we discuss a strategy, where
      clinical pharmacology can play an important role to improve the process of drug
      development.

PMID- 17186013
TI  - American Board of Clinical Pharmacology fellowship training and certification in
      clinical pharmacology: educational value and future needs for the discipline.
AB  - Currently, the training and education of young clinical pharmacologist who
      represent the future of our discipline rest almost entirely on
      institutions/organizations with established and productive fellowship training
      programs. Here, we discuss the role of the American Board of Clinical
      Pharmacology (ABCP) in accrediting fellowship training programs and certifying
      individual clinical pharmacologists. We also explore how ABCP certification adds
      value to both individual trainees and the discipline in the evolving world of
      clinical therapeutics and research in human pharmacology.

PMID- 17186014
TI  - The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene
      therapy of LNCaP prostate cancer cells without adverse effects in normal prostate
      epithelial cells.
AB  - Gene therapy of cancer using adenovirus as a single treatment modality has met
      limited success and efforts to enhance therapeutic outcomes have included
      combination of gene therapy with chemotherapy. The goal of this study was to
      investigate which chemotherapeutic agents may be suitable for combination with
      gene therapy of prostate cancer. Using an adenovirus expressing green fluorescent
      protein (GFP), we determined the effect of cisplatin, gemcitabine, doxorubicin,
      depsipeptide and MS-275 on adenoviral infectivity and transgene expression in
      LNCaP cells. We found that the two histone deacetylase inhibitors (HDACi),
      depsipeptide and MS-275, and to a lesser extent doxorubicin, increased
      infectivity and transgene expression. However, only the HDACi selectively
      increased infectivity in LNCaP cells while doxorubicin increased infectivity to a
      greater extent in normal prostate epithelial cells (PrEC). The increase in
      infectivity but not transgene expression correlated to increased surface
      expression of coxsackie and adenovirus receptor (CAR). Increased transgene
      expression following infection with an adenovirus expressing tumor necrosis
      factor-related apoptosis inducing ligand (TRAIL) was observed only in LNCaP cells
      treated with depsipeptide or MS-275. Combination of TRAIL gene therapy with HDACi
      but not doxorubicin resulted in increased induction of apoptosis in LNCaP cells.
      In contrast, apoptosis was not enhanced by HDACi in normal PrEC. These results
      suggest that combination of HDACi with adenoviral TRAIL gene therapy may be a new
      therapeutic approach for the treatment of prostate cancer that warrants further
      investigation.

PMID- 17186015
TI  - Apoptosis mediated by lentiviral TRAIL transfer involves transduction-dependent
      and -independent effects.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      anticancer agent, which selectively induces apoptosis in many transformed cells
      without apparent toxic side effects in normal tissue. We recently described the
      construction and characterization of a lentiviral vector for expression of TRAIL.
      In this report, we evaluate its suitability for therapeutic application. In
      vitro, we observed specific induction of apoptosis upon transduction in human
      lung cancer cells. Cell death was partially dependent on successful integration
      and TRAIL expression by the vectors, but was to some extent mediated by protein
      carryover, as we found TRAIL protein associated with virus particles.
      Transduction of subcutaneously growing lung tumors on nude mice with lentiviral
      TRAIL mediated a transient suppression of tumor growth. Analysis of tumor
      sections revealed that transduction efficiency of lentiviral control vector but
      not of lentiviral TRAIL vector was high. This was because of the direct cytotoxic
      activity of recombinant TRAIL present in viral particles, which prevented
      efficient tumor transduction. These data therefore suggest that enveloped viral
      vectors constitutively expressing TRAIL are well suited for ex vivo applications,
      such as the transduction of tumor-homing cells, but may have a lower effect when
      used directly for the transduction of tumor cells in vivo.

PMID- 17186016
TI  - The natural history of cervical HPV infection: unresolved issues.
AB  - The identification of high-risk human papillomavirus (HPV) types as a necessary
      cause of cervical cancer offers the prospect of effective primary prevention and
      the possibility of improving the efficiency of cervical screening programmes.
      However, for these opportunities to be realized, a more complete understanding of
      the natural history of HPV infection, and its relationship to the development of
      epithelial abnormalities of the cervix, is required. We discuss areas of
      uncertainty, and their possible effect on disease prevention strategies.

PMID- 17186017
TI  - Chemoprevention of breast cancer with selective oestrogen-receptor modulators.
AB  - Twenty years ago, a new therapeutic dimension was conceived that not only had the
      potential to treat and prevent osteoporosis, but to prevent breast and
      endometrial cancer at the same time. As osteoporosis was known to be caused by
      oestrogen withdrawal after menopause, whereas breast and endometrial cancer are
      caused by unopposed oestrogen action, the new tissue-selective oestrogens and
      anti-oestrogens, or selective oestrogen-receptor modulators (SERMs), had to
      recruit new networks to activate or suppress target tissues selectively. New
      medicines now promise to provide chemoprevention strategies for women at risk for
      the development of many diseases.

PMID- 17186018
TI  - The Connectivity Map: a new tool for biomedical research.
AB  - The ultimate objective of biomedical research is to connect human diseases with
      the genes that underlie them and drugs that treat them. But this remains a
      daunting task, and even the most inspired researchers still have to resort to
      laborious screens of genetic or chemical libraries. What if at least some parts
      of this screening process could be systematized and centralized? And hits found
      and hypotheses generated with something resembling an internet search engine?
      These are the questions the Connectivity Map project set out to answer.

PMID- 17186019
TI  - Understanding global nutrition dynamics as a step towards controlling cancer
      incidence.
AB  - As we look to understand future forces that will affect cancer risk, poor dietary
      patterns, overweight and obesity are significant concerns. In the past two
      decades these factors have shifted from issues that face higher-income countries
      to a global pandemic, and are rapidly becoming less a problem of affluence and
      more a problem of poverty. Rapid shifts in food systems, food pricing and
      marketing are the causes that underlie this trend. It is imperative to understand
      these factors and implement global interventions to slow this pandemic. The
      alternative is an acceleration of the incidence of the main nutrition-related
      cancers, primarily in developing countries.

PMID- 17186020
TI  - Activated Notch1 interacts with p53 to inhibit its phosphorylation and
      transactivation.
AB  - We propose a biochemical mechanism for the negative role of Notch signaling on
      p53 transactivation function. Expression of the intracellular domain of human
      Notch1 (Notch1-IC) inhibits the expression of p53-responsive genes p21, mdm2, and
      bax in HCT116 p53(-/-) cells. Furthermore, Notch1-IC expression inhibits the
      phosphorylation of ectopically expressed p53 in HCT116 p53(-/-) cells as well as
      the phosphorylation of endogenous p53 in UV-treated HCT116 p53(+/+) cells.
      Transcriptional downregulation of p53-responsive genes by Notch1-IC was confirmed
      both by chromatin immunoprecipitation assay and Northern blot analysis. We found
      the intracellular interaction between Notch1-IC and p53 in HCT116 p53(+/+) cells
      and suggest that activated Notch1 interaction with p53 is an important cellular
      event for the inhibition of p53-dependent transactivation. The N-terminal
      fragment of Notch1-IC, which can interacts with p53, inhibits p53 phosphorylation
      and represses p53 transactivation. In addition, Notch signaling downregulated p53
      dependent apoptosis induced by UV irradiation.

PMID- 17186021
TI  - Human neural progenitor cells display limited cytotoxicity and increased
      oligodendrogenesis during inflammation.

PMID- 17186022
TI  - Downregulation of Bid is associated with PKCepsilon-mediated TRAIL resistance.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      anticancer agent as it selectively kills tumor cells but spares normal cells.
      Resistance to TRAIL by tumor cells limits its therapeutic use. We have previously
      shown that protein kinase C-epsilon (PKCepsilon) acts as an antiapoptotic protein
      in MCF-7 breast cancer cells. In the present study, we have investigated the
      mechanism(s) by which PKCepsilon contributes to TRAIL resistance. Overexpression
      of PKCepsilon inhibited caspase-8 and -9 activation, release of mitochondrial
      cytochrome c and cell death induced by TRAIL, but did not interfere with the
      recruitment of caspase-8 to the death-inducing signaling complex.
      Knockdown/inhibition of PKCepsilon resulted in enhanced sensitivity to TRAIL. The
      level of Bcl-2 was increased and Bid was decreased by PKCepsilon at both the
      protein and mRNA level but PKCepsilon had no effect on Bax. Knockdown of Bcl-2 by
      siRNA reversed TRAIL resistance in PKCepsilon-overexpressing cells, whereas
      depletion of Bid contributed to TRAIL resistance in MCF-7 cells. A decrease in
      Bid content was also associated with inhibition of TRAIL-induced caspase-8
      activation. Furthermore, PKCepsilon depletion or overexpression of DN-PKCepsilon
      was associated with a decrease in Bcl-2 protein level. Thus, our results suggest
      that PKCepsilon acts upstream of mitochondria and mediates TRAIL resistance via
      both Bcl-2 and Bid in MCF-7 cells.

PMID- 17186023
TI  - Regulation of developmental rate and germ cell proliferation in Caenorhabditis
      elegans by the p53 gene network.
AB  - Caenorhabditis elegans CEP-1 activates germline apoptosis in response to
      genotoxic stress, similar to its mammalian counterpart, tumor suppressor p53. In
      mammals, there are three p53 family members (p53, p63, and p73) that activate and
      repress many distinct and overlapping sets of genes, revealing a complex
      transcriptional regulatory network. Because CEP-1 is the sole p53 family member
      in C. elegans, analysis of this network is greatly simplified in this organism.
      We found that CEP-1 functions during normal development in the absence of stress
      to repress many (331) genes and activate only a few (28) genes. In response to
      genotoxic stress, 1394 genes are activated and 942 are repressed, many of which
      contain p53-binding sites. Comparison of the CEP-1 transcriptional network with
      transcriptional targets of the human p53 family reveals considerable overlap
      between CEP-1-regulated genes and homologues regulated by human p63 and p53,
      suggesting a composite p53/p63 action for CEP-1. We found that phg-1, the C.
      elegans Gas1 (growth arrest-specific 1) homologue, is activated by CEP-1 and is a
      negative regulator of cell proliferation in the germline in response to genotoxic
      stress. Further, we find that CEP-1 and PHG-1 mediate the decreased developmental
      rate and embryonic viability of mutations in the clk-2/TEL2 gene, which regulates
      lifespan and checkpoint responses.

PMID- 17186024
TI  - Nuclear PTEN: a tale of many tails.

PMID- 17186025
TI  - Regulation of Nod1-mediated signaling pathways.
AB  - Nod1 is a member of the NLR/Nod/CATERPILLER family. It acts as a sensor for
      intracellular bacteria by recognizing specific glycopeptides derived from
      peptidoglycan. Nod1 activation mediates distinct cellular responses including
      activation of MAP kinases, IL-8 release, apoptosis and suppression of several
      estrogen-dependent responses in MCF-7 cells. Here we have extended these studies
      by identifying key regulatory steps in Nod1-dependent signaling pathways. We
      provide multiple lines of data showing that Nod1-dependent apoptosis is a caspase
      8-mediated event and that apoptosis requires RIP2. In contrast, several lines of
      evidence show that Nod1-dependent JNK activation and IL-8 production did not
      require the presence of caspase 8 but required activation of TAK1 as well as
      RIP2. Thus, we have identified several key control points that lie downstream of
      Nod1. This work provides the basis for further studies of the biological
      significance and regulation of the Nod1 pathway.

PMID- 17186026
TI  - Acidic residues of yeast frataxin have an essential role in Fe-S cluster
      assembly.
AB  - Friedreich ataxia is caused by decreased levels of frataxin, a mitochondrial
      acidic protein that is assumed to act as chaperone in the assembly of Fe-S
      clusters on the scaffold Isu protein. Frataxin has the in vitro capacity to form
      iron-loaded multimers, which also suggests an iron storage function. It has been
      reported that alanine substitution of residues in an acidic ridge of yeast
      frataxin (Yfh1) elicits loss of iron binding in vitro but has no effect on Fe-S
      cluster synthesis in vivo. Here, we show that a marked change in the
      electrostatic properties of a specific region of Yfh1 surface - by substituting
      two or four acidic residues by lysine or alanine, respectively - impairs Fe-S
      cluster assembly, weakens the interaction between Yfh1 and Isu1, and increases
      oxidative damage. Therefore, the acidic ridge is essential for the Yfh1 function
      and is likely to be involved in iron-mediated protein-protein interactions.

PMID- 17186027
TI  - Herpes simplex virus eliminates host mitochondrial DNA.
AB  - Mitochondria have crucial roles in the life and death of mammalian cells, and
      help to orchestrate host antiviral defences. Here, we show that the ubiquitous
      human pathogen herpes simplex virus (HSV) induces rapid and complete degradation
      of host mitochondrial DNA during productive infection of cultured mammalian
      cells. The depletion of mitochondrial DNA requires the viral UL12 gene, which
      encodes a conserved nuclease with orthologues in all herpesviruses. We show that
      an amino-terminally truncated UL12 isoform-UL12.5-localizes to mitochondria and
      triggers mitochondrial DNA depletion in the absence of other HSV gene products.
      By contrast, full-length UL12, a nuclear protein, has little or no effect on
      mitochondrial DNA levels. Our data document that HSV inflicts massive genetic
      damage to a crucial host organelle and show a novel mechanism of virus-induced
      shutoff of host functions, which is likely to contribute to the cell death and
      tissue damage caused by this widespread human pathogen.

PMID- 17186028
TI  - Amplification of apoptosis through sequential caspase cleavage of the MET
      tyrosine kinase receptor.
AB  - Activation of the MET tyrosine kinase receptor by hepatocyte growth
      factor/scatter factor is classically associated with cell survival. Nonetheless,
      stress stimuli can lead to a caspase-dependent cleavage of MET within its
      juxtamembrane region, which generate a proapoptotic 40 kDa fragment (p40 MET). We
      report here that p40 MET is in fact generated through an additional caspase
      cleavage of MET within its extreme C-terminal region, which removes only few
      amino acids. We evidenced a hierarchical organization of these cleavages, with
      the C-terminal cleavage favoring the juxtamembrane one. As a functional
      consequence, the removal of the last amino acids of p40 MET increases its
      apoptotic capacity. Finally, cells expressing a MET receptor mutated at the C
      terminal caspase site are unable to generate p40 MET and are resistant to
      apoptosis, indicating that generation of p40 MET amplifies apoptosis. These
      results revealed a two-step caspase cleavage of MET resulting in the reshaping of
      this survival receptor to a proapoptotic factor.

PMID- 17186029
TI  - Inflammasome adaptors and sensors: intracellular regulators of infection and
      inflammation.
AB  - The NOD-like receptors have important roles in innate immunity as intracellular
      sensors of microbial components and cell injury. It has been proposed that these
      cytosolic proteins regulate the cysteine protease caspase-1 within a multiprotein
      complex known as the 'inflammasome'. Activation of caspase-1 leads to the
      cleavage and activation of pro-inflammatory cytokines such as interleukin-1beta
      (IL-1beta) and IL-18, as well as host-cell death. The analysis of mice that are
      deficient in various inflammasome components has revealed that the inflammasome
      is a dynamic entity that is assembled from different adaptors in a stimulus
      dependent manner. Here we review recent work on the activation of the
      inflammasome in response to various bacterial pathogens and tissue damage.

PMID- 17186030
TI  - Crosstalk between cancer and immune cells: role of STAT3 in the tumour
      microenvironment.
AB  - Immune cells in the tumour microenvironment not only fail to mount an effective
      anti-tumour immune response, but also interact intimately with the transformed
      cells to promote oncogenesis actively. Signal transducer and activator of
      transcription 3 (STAT3), which is a point of convergence for numerous oncogenic
      signalling pathways, is constitutively activated both in tumour cells and in
      immune cells in the tumour microenvironment. Constitutively activated STAT3
      inhibits the expression of mediators necessary for immune activation against
      tumour cells. Furthermore, STAT3 activity promotes the production of
      immunosuppressive factors that activate STAT3 in diverse immune-cell subsets,
      altering gene-expression programmes and, thereby, restraining anti-tumour immune
      responses. As such, STAT3 propagates several levels of crosstalk between tumour
      cells and their immunological microenvironment, leading to tumour-induced
      immunosuppression. Consequently, STAT3 has emerged as a promising target for
      cancer immunotherapy.

PMID- 17186031
TI  - Regulation of immune tolerance by anti-inflammatory neuropeptides.
AB  - The induction of antigen-specific tolerance is essential to maintain immune
      homeostasis, control autoreactive T cells, prevent the onset of autoimmune
      diseases and achieve tolerance of transplants. Inflammation is a necessary
      process for eliminating pathogens, but can lead to serious deleterious effects in
      the host if left unchecked. Identifying the endogenous factors that control
      immune tolerance and inflammation is a key goal in the field of immunology. In
      the last decade, various neuropeptides that are produced by immune cells with
      potent anti-inflammatory actions were found to participate in the maintenance of
      tolerance in different immunological disorders.

PMID- 17186032
TI  - Identifying and hurdling obstacles to translational research.
AB  - Although there is overwhelming pressure from funding agencies and the general
      public for scientists to bridge basic and translational studies, the fact remains
      that there are significant hurdles to overcome in order to achieve this goal. The
      purpose of this Opinion article is to examine the nature of these hurdles and to
      provide food for thought on the main obstacles that impede this process.

PMID- 17186034
TI  - Noise suppression properties of an interferometer-based regenerator for
      differential phase-shift keying data.
AB  - We studied the amplitude and phase noise suppression properties of an all-optical
      regenerator for differential phase-shift keying data. A detailed analytical
      investigation is performed and compared with numerical simulations for different
      working points. The results show that both amplitude and phase can be
      regenerated. However, simultaneous amplitude and phase noise suppression is
      possible only if the phase degradation is stronger than the amplitude
      degradation, for instance, due to nonlinear phase noise.

PMID- 17186035
TI  - Fusion splicing small-core photonic crystal fibers and single-mode fibers by
      repeated arc discharges.
AB  - We demonstrate a novel method for low-loss splicing small-core photonic crystal
      fibers (PCFs) and single-mode fibers (SMFs) by repeated arc discharges using a
      conventional fusion splicer. An optimum mode field match at the interface of PCF
      SMF and an adiabatic mode field variation in the longitudinal direction of the
      small-core PCF can be achieved by repeated arc discharges applied over the
      splicing joint to gradually collapse the air holes of the small-core PCF. This
      method is simple and offers a practical solution for light coupling between small
      core PCFs and SMFs.

PMID- 17186033
TI  - Prospective for biodegradable microstructured optical fibers.
AB  - We report fabrication of a novel microstructured optical fiber made of
      biodegradable and water soluble materials that features approximately 1 dB/cm
      transmission loss. Two cellulose butyrate tubes separated with hydroxypropyl
      cellulose powder were codrawn into a porous double-core fiber offering
      integration of optical, microfluidic, and potentially drug release
      functionalities.

PMID- 17186036
TI  - Analysis of nonlinear gain-induced effects on short-pulse amplification in doped
      fibers by use of an extended power equation.
AB  - Optical pulse amplification in doped fibers is studied using an extended power
      transport equation for the coupled pulse spectral components. This equation
      includes the effects of gain saturation, gain dispersion, fiber dispersion, fiber
      nonlinearity, and amplified spontaneous emission. The new model is employed to
      study nonlinear gain-induced effects on the spectrotemporal characteristics of
      amplified subpicosecond pulses, in both the anomalous and the normal dispersion
      regimes.

PMID- 17186037
TI  - Binary image restoration by positive semidefinite programming.
AB  - We report an optimization approach to restore degraded binary images by using
      positive semidefinite programming when the point spread function (PSF) is known.
      The approach takes advantage of the combinatorial nature of the problem,
      considering not only local similarity and spatial context but also the
      relationship between individual pixel values and the PSF. Numerical experiments
      confirm the superiority of the approach.

PMID- 17186039
TI  - Sequential demodulation of a single fringe pattern guided by local frequencies.
AB  - A simple but effective approach for the demodulation of a single fringe pattern
      is proposed. The phase with an undetermined sign is directly obtained by taking
      the arccosine value of a preprocessed fringe pattern. The local frequencies, also
      with an undetermined sign, are then estimated by local matching. The sign
      ambiguity is then removed simply by forcing the continuity of the local
      frequencies. The priority of sign determination is guided by the value of total
      local frequency (fringe density) so that the critical points are processed last.
      The proposed approach is verified by successful demodulation of a simulated
      fringe pattern and two experimental fringe patterns.

PMID- 17186038
TI  - Evanescent imaging with induced polarization by using a solid immersion lens.
AB  - Image contrast enhancement, high lateral resolution, and height information are
      obtained with induced polarization evanescent imaging using a solid immersion
      lens. Experiments are conducted by imaging features on a patterned Si substrate.
      Imaging theory is used to predict optimum orientation of high-spatial-frequency
      samples, and a topographical image is derived from the induced polarization image
      through a calibration procedure. A numerical aperture of 1.5 is used in the
      experiment. Height accuracy of +/-2 nm is demonstrated with a known sample.

PMID- 17186040
TI  - Polarization modulation imaging ellipsometer.
AB  - The polarization modulation technique was successfully combined with parallel
      synchronous detection using a switching light source and a CCD camera to realize
      full-frame measurement of ellipsometric parameters. The detected thickness of a
      monolayer film of n-octadecylsiloxane agreed well with theoretical and reported
      experimental values. The thickness resolution for imaging and the temporal noise
      in parallel thickness measurements were smaller than +/-0.1 nm and smaller than
      +/-0.02 nm, respectively.

PMID- 17186041
TI  - Dispersion and loss limitations on the performance of optical delay lines based
      on coupled resonant structures.
AB  - The relative importance of group-velocity dispersion and loss-induced distortion
      in limiting the performance of optical delay lines based on coupled resonator
      structures is investigated. It is shown that for the current state of the quality
      of fabrication both factors play roughly comparable roles for bit rates of 2.5-40
      Gbits/s and that as the storage capacity grows, the relative weight of loss
      imposed limitation increases.

PMID- 17186042
TI  - Gigahertz modulation of GaAs-based bipolar cascade vertical cavity surface
      emitting lasers.
AB  - The high-frequency modulation characteristics of GaAs-based bipolar cascade
      vertical cavity surface-emitting lasers operating at 980 nm with GaAs tunnel
      junctions and p-doped Al0.98Ga0.02As oxide apertures have been measured. We
      achieve -3 dB laser output modulations of 6.5 GHz for two-stage and 9.4 GHz for
      three-stage devices in response to small-signal current injection at an operating
      temperature of -50 degrees C.

PMID- 17186043
TI  - Optimization toward a high-average-brightness soft-x-ray laser pumped at grazing
      incidence.
AB  - We report the near-field imaging characterization of a 10 Hz Ni-like 18.9 nm
      molybdenum soft-x-ray laser pumped in a grazing incidence pumping (GRIP) geometry
      with a table-top laser driver. We investigate the effect of varying the GRIP
      angle on the spatial behavior of the soft-x-ray laser source. After
      multiparameter optimization, we were able to find conditions to generate
      routinely a high-repetition-rate soft-x-ray laser with an energy level of up to 3
      microJ/pulse and to 6x10(17) photons/s/mm2/mrad2/(0.1% bandwidth) average
      brightness and 1x10(28) photons/s/mm2/mrad2/(0.1% bandwidth) peak brightness.

PMID- 17186044
TI  - Fractal model of light scattering in biological tissue and cells.
AB  - The K-distribution, widely used for investigation of fractal scattering in the
      atmosphere and from surfaces, is applied as a model for light propagation in
      biological tissue and cells. This leads to simple expressions for the scattering
      function, anisotropy function, phase function, reduced scattering coefficient,
      and scattering power. Compared with an alternative previously published model
      [Opt. Lett.30, 3051 (2005)], the range of allowable power laws is extended into
      the subfractal regime.

PMID- 17186045
TI  - Feedback localization of freely diffusing fluorescent particles near the optical
      shot-noise limit.
AB  - We report near-optimal tracking of freely diffusing fluorescent particles in a
      quasi-two-dimensional geometry via photon counting and real-time feedback. We
      present a quantitative statistical model of our feedback network and find
      excellent agreement with the experiment. We monitor the motion of a single
      fluorescent particle with a sensitivity of 15 nm/sqrt Hz while collecting fewer
      than 5000 fluorescence photons/s. Fluorescent microspheres (diffusion coefficient
      1.3 microm2/s) are tracked with a root-mean-square tracking error of 170 nm,
      within a factor of 2 of the theoretical limit set by photon counting shot noise.

PMID- 17186046
TI  - Carbon nanotube mode lockers with enhanced nonlinearity via evanescent field
      interaction in D-shaped fibers.
AB  - We demonstrate a novel passive mode-locking scheme for pulsed lasers enhanced by
      the interaction of carbon nanotubes (CNTs) with the evanescent field of
      propagating light in a D-shaped optical fiber. The scheme features all-fiber
      operation as well as a long lateral interaction length, which guarantees a strong
      nonlinear effect from the nanotubes. Mode locking is achieved with less than 30%
      of the CNTs compared with the amount of nanotubes used for conventional schemes.
      Our method also ensures the preservation of the original morphology of the
      individual CNTs. The demonstrated pulsed laser with our CNT mode locker has a
      repetition rate of 5.88 MHz and a temporal pulse width of 470 fs.

PMID- 17186047
TI  - Effect of an optical negative index thin film on optical bistability.
AB  - We investigate nonlinear transmission in a layered structure consisting of a slab
      of positive index material with Kerr-type nonlinearity and a subwavelength layer
      of linear negative index material (NIM) sandwiched between semi-infinite linear
      dielectrics. We find that a thin layer of NIM leads to significant changes in the
      hysteresis width when the nonlinear slab is illuminated at an angle near that of
      total internal reflection. Unidirectional diodelike transmission with enhanced
      operational range is demonstrated. These results may be useful for NIMs
      characterization and for designing novel NIMs-based devices.

PMID- 17186048
TI  - Boundary force effects exerted on solitons in highly nonlinear media.
AB  - We study the effects caused by remote boundaries on soliton dynamics in nonlinear
      media with a large range of nonlocality, and demonstrate theoretically and
      experimentally how asymmetric boundary forces can lead to soliton steering and
      oscillation in predetermined trajectories.

PMID- 17186049
TI  - Parametric oscillations in a whispering gallery resonator.
AB  - We demonstrate strongly nondegenerate optical continuous-wave parametric
      oscillations in crystalline whispering gallery mode resonators fabricated from
      LiNbO3. The required phase matching is achieved by geometrical confinement of the
      modes in the resonator.

PMID- 17186050
TI  - Optical noise reduction for dc-removed coaxial holographic data storage.
AB  - A method of reconstructing positive and negative images from Fourier holograms
      recorded without the dc components is demonstrated by use of a coaxial
      holographic storage system. Reconstructed images are obtained by adding a phase
      modulated dc component of the signal beam on reading. Contrast reversal of the
      reconstructed images can be achieved by reversing the readout reference pattern.
      This method can realize not only optical noise reduction but also less
      consumption of the dynamic range of the recording medium, potentially
      contributing to increasing the number of multiplexed holograms.

PMID- 17186051
TI  - Power dissipation in slow light devices: a comparative analysis.
AB  - The performance of various slow light schemes is analyzed from the point of view
      of power dissipation per stored bit. It is shown that the dissipated power
      increases quite nonlinearly with storage capacity, and that the schemes based on
      low-loss photonic structures with distributed amplifiers hold indisputable
      advantage over other schemes.

PMID- 17186052
TI  - Ultralow-threshold Raman lasing with CaF2 resonators.
AB  - We demonstrate efficient Raman lasing with CaF2 whispering-gallery-mode
      resonators. Continuous-wave emission threshold is shown to be possible below 1
      microW with a 5mm cavity, which is to our knowledge orders of magnitude lower
      than in any other Raman source. Low-threshold lasing is made possible by the
      ultrahigh optical quality factor of the cavity, of the order of Q=5x10(10).
      Stokes components of up to the fifth order were observed at a pump power of 160
      microW, and up to the eighth order at 1 mW. A lasing threshold of 15 microW was
      also observed in a 100 microm CaF2 microcavity. Potential applications are
      discussed.

PMID- 17186053
TI  - High-efficiency 1.5 microm thick optical axis grating and its use for laser beam
      combining.
AB  - We demonstrate an optical axis grating (OAG) recorded in a nematic liquid crystal
      that yields a higher than 80% diffraction efficiency and over 800:1 switching
      contrast between diffraction orders for a laser beam of a red wavelength in a
      material layer only 1.5 microm thick. The grating was used for combining two
      laser beams with high efficiency. These observations prove the feasibility of new
      generation high-efficiency diffractive optical components, which are most
      promising for infrared and high-power applications owing to their enhanced
      transparency and reduced thermal effects in thin material layers.

PMID- 17186054
TI  - Extraordinary optical transmission in the ultraviolet region through aluminum
      hole arrays.
AB  - We investigated the extraordinary optical transmission phenomenon in the UV range
      by fabricating large-area, free-standing aluminum hole arrays using extreme UV
      interference lithography and shadow thermal evaporation. Transmission spectra
      show strong peaks in the UV region resulting from both surface plasmon polariton
      and localized surface plasmon excitations. The results indicate that the high
      plasmon frequency of Al is directly responsible for the presence of strong
      resonance peaks in the UV region, which supports the role of plasmonic phenomena
      in the extraordinary transmission. The simple fabrication method enables large
      area production of such structures for research and industrial production
      purposes.

PMID- 17186055
TI  - Effective signal-to-noise ratio improvement by parametric image amplification.
AB  - We show experimentally that parametric optical preamplification greatly improves
      the signal-to-noise ratio of an image if the detector has a poor quantum
      efficiency and/or a great level of readout noise. Results are fully consistent
      with the theory of quantum-noise-limited amplification.

PMID- 17186056
TI  - Strong relative intensity squeezing by four-wave mixing in rubidium vapor.
AB  - We have measured -3.5 dB (-8.1 dB corrected for losses) relative intensity
      squeezing between probe and conjugate beams generated by stimulated,
      nondegenerate four-wave mixing in hot rubidium vapor. Unlike early observations
      of squeezing in atomic vapors based on saturation of a two-level system, our
      scheme uses a resonant nonlinearity based on ground-state coherences in a three
      level system. Since this scheme produces narrowband, squeezed light near an
      atomic resonance, it is of interest for experiments involving cold atoms or
      atomic ensembles.

PMID- 17186057
TI  - Compact spectral shearing interferometer for ultrashort pulse characterization.
AB  - A simple, compact, and robust implementation of spectral shearing interferometry
      using a single nonlinear crystal for both ancilla generation and upconversion is
      demonstrated. The device is capable of accurate characterization of femtosecond
      laser pulses over the 740-900 nm range with a KDP crystal.

PMID- 17186058
TI  - Stimulated Raman X waves in ultrashort optical pulse filamentation.
AB  - We demonstrate that ultrashort pulse filamentation in liquids with strong Raman
      gain leads to the spontaneous formation of nonlinear X waves at a Raman-shifted
      wavelength. We measured as much as 75% energy conversion efficiency into a Raman
      X wave in ethanol starting from 1 ps pulses due to the group velocity matching
      between the pump and Raman X pulses. Large Raman gain of a weak seed signal was
      observed in water, associated with a strong spatiotemporal transformation of the
      seed into an X wave.

PMID- 17186059
TI  - Third-harmonic generation in disguise of second-harmonic generation revisited:
      role of thin-film thickness and carrier-envelope phase.
AB  - It has previously been reported that a peak at the spectral position of the
      second harmonic of an excitation laser can be generated in an inversion-symmetric
      medium in the regime of extreme nonlinear optics and that this peak may be
      exploited to measure the carrier-envelope phase of the excitation pulse. Here we
      revisit this phenomenon with regard to reverse engineering the carrier-envelope
      phase and demonstrate that the thin-film thickness and the incident field can
      have a drastic influence on pulse propagation, and so the reverse engineering
      would likely fail.

PMID- 17186060
TI  - Photochemistry of refractive index structures in poly(methyl methacrylate) by
      femtosecond laser irradiation.
AB  - Femtosecond, subablation threshold photomodification of poly(methyl methacrylate)
      (PMMA) at 387 nm is explored to enable fabrication of optical components.
      Volatile fragment analysis (thermal desorption gas chromatography-mass
      spectrometry) and molecular weight distribution monitoring (size exclusion
      chromatography) suggest photochemical modification, involving direct cleavage of
      the polymer backbone and propagation via chain unzipping under formation of
      monomers, similar to the pyrolytic degradation of PMMA. Waveguides were produced
      in undoped, clinical-grade PMMA, showing an increased refractive index in the
      laser focal region (Dnmax=4x10(-3)).

PMID- 17186062
TI  - Changes in Marijuana Use Over the Transition Into Marriage.
AB  - Reductions in substance use tend to coincide with marriage, as both may occur
      during emerging adulthood. During the transition to marriage, it is possible that
      one's spouse may be the influence that causes the reduction in substance use.
      Data on participants (N = 471 couples) for this report are taken from a
      longitudinal study of early marriage. The objective of the current analysis is to
      determine if having a spouse who uses marijuana is associated with a greater
      likelihood of one's own use. Additionally, we are interested in spousal influence
      and cessation. The findings support spousal influence. Husbands are more likely
      to start using marijuana if their wives use marijuana, but the reverse is not
      true. Husbands also are more likely to stop using if their spouses do not use.
      During the transition into marriage, the drug use of one spouse does affect the
      other. However, this influence appears to be unidirectional, with wives
      influencing their husbands more often.

PMID- 17186063
TI  - Pupillary contagion: central mechanisms engaged in sadness processing.
AB  - Empathic responses underlie our ability to share emotions and sensations with
      others. We investigated whether observed pupil size modulates our perception of
      other's emotional expressions and examined the central mechanisms modulated by
      incidental perception of pupil size in emotional facial expressions. We show that
      diminishing pupil size enhances ratings of emotional intensity and valence for
      sad, but not happy, angry or neutral facial expressions. This effect was
      associated with modulation of neural activity within cortical and subcortical
      regions implicated in social cognition. In an identical context, we show that the
      observed pupil size was mirrored by the observers' own pupil size. This
      empathetic contagion engaged the brainstem pupillary control nuclei (Edinger
      Westphal) in proportion to individual subject's sensitivity to this effect. These
      findings provide evidence that perception-action mechanisms extend to non
      volitional operations of the autonomic nervous system.

PMID- 17186064
TI  - Molecular Mechanisms for Altered Glucose Homeostasis in HIV Infection.
AB  - A complete understanding of the molecular mechanisms leading to HIV-associated
      insulin resistance remains elusive. Complex interrelationships between genetic
      predisposition, disease-related body changes and multidrug therapy all contribute
      to alterations in glucose homeostasis. These abnormalities can be differentiated
      between acute and reversible changes directly induced by HAART medications and
      more chronic and less reversible changes due to the development of lipodystrophy
      and hyperlipidemia. Implicated pathways include changes in adipokine secretion,
      insulin signaling, lipid homeostasis and disease-related increases in
      inflammatory mediators. The insulin responsive facilitative glucose transporter
      GLUT4 is the first molecule to have been identified as a direct target of HIV
      protease inhibitors. Efforts to elucidate the mechanisms directly responsible for
      the evolution of insulin resistance during HIV infection and therapy will be
      greatly assisted by the further identification and characterization of direct
      molecular targets amenable to pharmacologic therapy and/or the development of
      newer antiretroviral agents that do not adversely affect these target proteins.

PMID- 17186065
TI  - Functional nanostructures from surface chemistry patterning.
AB  - Nanoscale devices are expected to provide important advances for a number of
      applications. While many methods to generate nanoscale patterns exist, their use
      is confined to a relatively narrow range of materials. To fabricate nanoscale
      structures of a material with useful properties, the most convenient route is to
      transfer the geometry of an existing pattern into another material. Methods to
      achieve this pattern transfer are summarized and organized in this review.
      Methods to generate the original patterns, as well as applications of the final
      structure are also described.

PMID- 17186066
TI  - Modelling studies of water in crystalline nanoporous aluminosilicates.
AB  - The paper presents a review of molecular modelling studies of hydrated nanoporous
      aluminosilicates (zeolites and clays) performed during the last decade. A special
      emphasis is set on the calculation of the dynamical quantities and collective
      properties of the confined water. Some new results concerning the behaviour of
      water molecules in the siliceous silicalite and zeolite beta structures are
      presented.

PMID- 17186067
TI  - Identification of the surface species responsible for N2O formation from the
      chemisorption of NO on Rh/alumina.
AB  - Energy dispersive EXAFS (EDE) and diffuse reflectance infrared spectroscopy
      (DRIFTS) are combined synchronously at high time resolution (17 Hz) to probe how
      NO(g) reacts with gamma-Al(2)O(3) supported, metallic Rh nanoparticles of an
      average 11 A diameter; a bent nitrosyl species is considered to be the key to the
      formation of N(2)O.

PMID- 17186068
TI  - Disentangling mode-specific reaction dynamics from overlapped images.
AB  - The hydrogen abstraction reaction between atomic chlorine and C-H stretch-excited
      CHD(3) was studied under crossed-beam conditions. Prior to collisions, an
      infrared (IR) laser was used to pump up a fraction of CHD(3) to nu(1) = 1. A time
      sliced velocity imaging technique was exploited to image the recoil velocity
      distribution of the state-selected product CD(3)(nu = 0). For energetic reasons,
      the IR-on image shows severely overlapped features arising from both the excited
      and the un-pumped ground-state reagents. A novel threshold method was then
      developed to directly determine the fraction of IR-excited CHD(3) reagents, which
      in turn enables us to disentangle the state-selected dynamics from the overlapped
      images. The results reveal significant differences from previous experimental
      reports.

PMID- 17186069
TI  - Collisional energy transfer in the intermediate states used for optical-optical
      double resonance excitation of ion-pair states in I2.
AB  - The optical-optical double resonance spectra of I(2) and I(2)-Xe mixtures at room
      temperature reported in the literature using a fixed-wavelength, broad band pump
      laser have now been recorded using a tuneable, narrow band source. We show that
      during the time of the overlapped laser pulses ( approximately 10 ns) and with 10
      20 Torr of Xe there is widespread collisional energy transfer in the intermediate
      state and that this phenomenon offers an alternative explanation for the broad
      bands in the excitation spectrum, assigned to XeI(2) complexes by the authors of
      the earlier study (M. E. Akopyan, I. Y. Novikova, S. A. Poretsky and A. M.
      Pravilov, Chem. Phys., 2005, 310, 287). Dispersed emission bands, previously
      attributed to direct fluorescence from the ion-pair state(s) of the complexes,
      are re-assigned to emission from ion-pair states of the parent I(2) that are
      populated by collisional energy transfer out of the initially excited state.

PMID- 17186070
TI  - Photodissociation dynamics of methyl nitrate at 193 nm: energy disposal in
      methoxy and nitrogen dioxide products.
AB  - The photodissociation dynamics of methyl nitrate, CH(3)ONO(2), has been
      investigated at 193 nm by examining the products from the primary dissociation
      channel, namely CH(3)O and NO(2). The CH(3)O (X (2)E) photoproducts were probed
      by laser-induced fluorescence (LIF) on the A (2)A(1)-X (2)E transition under both
      nascent and jet-cooled conditions. The 3 and 3 bands originating from the
      vibrationless and C-O stretch (nu(3)) levels, respectively, were characterized to
      obtain the internal energy distribution of the CH(3)O products. Only a small
      fraction of the CH(3)O products (< or =10%) were produced with one quantum of C-O
      stretch excitation as determined from the relative intensities of the bands in
      combination with transition probabilities derived from dispersed fluorescence
      measurements and/or calculated Franck-Condon factors. The CH(3)O products also
      had minimal rotational excitation: those produced in the ground vibrational state
      had a rotational temperature of 238 +/- 7 K, corresponding to less than 1% of the
      available energy. Products with C-O stretch excitation were found to have a
      higher rotational temperature, but still a small fraction of the total energy.
      Combining the CH(3)O internal energy findings with previous photofragment
      translational energy measurements [X. Yang, P. Felder and J. R. Huber, J. Phys.
      Chem., 1993, 97, 10903] indicates that most of the available energy is deposited
      in the NO(2) fragment. This is verified through dispersed fluorescence
      measurements which show that the NO(2) fragment is produced electronically
      excited with internal energies extending to the NO + O dissociation limit. Ab
      initio calculations confirm that the dominant initial excitation is strongly
      localized on the NO(2) moiety. The calculations are also used to reveal the
      forces that give rise to internal excitation of the CH(3)O fragment upon
      electronic excitation.

PMID- 17186071
TI  - Coherent and incoherent orientation and alignment of ICN photoproducts.
AB  - We report extended measurements of the rotational polarization and correlated
      angular distribution of CN photofragments from ICN photodissociation, with a
      particular emphasis on the creation and detection of molecular orientation with
      circularly-polarized light. Doppler profiles of the nascent photoproducts are
      measured by Frequency-Modulated (FM) transient absorption, and the resulting high
      signal-to-noise data are valuable for verifying the form of the angular
      correlations between the recoil velocity, the photofragment rotational angular
      momentum, and the space-fixed frame defined by the dissociation polarization. A
      space-fixed bipolar moment notation can be used for an unambiguous
      characterization of the maximal set of polarization properties that can be
      created with one-photon excitation and detected with one-photon Doppler-resolved
      absorption spectroscopy. Relating the observed polarization moments to the
      various coherent and incoherent, adiabatic and non-adiabatic mechanisms, that
      have been derived and verified extensively in the case of diatomic
      photodissociation to polarized atomic fragments, is not unambiguous in the case
      of diatomic fragments from triatomic precursors. Constraints among various
      polarization moments confirmed in the case of diatomic dissociation are not
      confirmed in this triatomic case, where the perpendicular transitions to non
      degenerate A' and A'' components of a linear Omega = 1 state are qualitatively
      different from excitation to degenerate Omega = +/-1 states in a diatomic
      molecule.

PMID- 17186072
TI  - Photoionization versus photoheterolysis of all-trans-retinol. The effects of
      solvent and laser radiation intensity.
AB  - The time-resolved formation of the retinyl carbocation from all-trans-retinol and
      all-trans-retinol acetate was studied by use of picosecond flash photolysis. From
      both precursors, the retinyl cation is produced by heterolytic C-O bond cleavage
      in solvents of medium polarity (acetonitrile, tetrahydrofuran, propanol with
      Reichardt polarity parameter ET(N) approximately 0.5) and high polarity (EtOH,
      MeOH, TFE, HFIP, ET(N) > 0.6) during the laser pulse (< or =5 ps) where its
      lifetime is >10 ns. The absorption maximum of the cation at early times (t < 100
      ps) is at lambda = 590-600 nm; it shifts to shorter wavelengths (Deltalambda = 5
      10 nm) within 1-10 ns. This spectral shift is suggested to be due to contact ion
      pair --> solvent-separated ion pair --> free-ion transformation. The quantum
      yield of cation formation phi(cat) is independent of excitation wavelength (213,
      266 or 355 nm). Photoheterolysis proceeds via a one-quantum process. In
      chlorinated solvents, i.e. n-BuCl, 1,2-dichloroethane, chloroform or CCl(4),
      formation of the retinol radical cation (which is characterized by a peak at 610
      nm and further absorption maxima at approximately 840 and approximately 940 nm)
      by intermolecular electron transfer to the solvent molecules was detected. The
      radical cation lifetime in all these solvents is 1.5-2 ns, except for CCl(4)
      where it is 0.25 ns. The formation of the radical cation or cation was not
      detected in the low polarity solvents: cyclohexane, hexane, dioxane and p-xylene.
      However, in solvents of medium and high polarity, at high radiation intensities
      the radical cation may form in addition to the cation (as a result of two-quantum
      ionization). DFT calculations confirm our experimental results. The rate of
      retinol S(1) depopulation (k = 0.3-1 x 10(9) s(-1)) is almost independent of the
      solvent polarity in the range from cyclohexane to methanol. In highly polar
      solvents (ET(N) > 0.9) the rate increases to (0.5-5) x 10(10) s(-1).

PMID- 17186073
TI  - Correlated proton motion in hydrogen bonded systems: tuning proton affinities.
AB  - The theorem of matching proton affinities (PA) has been widely used in the
      analysis of hydrogen bonds. However, most experimental and theoretical
      investigations have to cope with the problem that the variation of the PA of one
      partner in the hydrogen bond severely affects the properties of the interface
      between both molecules. The B3LYP/d95+(d,p) analysis of two hydrogen bonds
      coupled by a 5-methyl-1H-imidazole molecule showed that it is possible to change
      the PA of one partner of the hydrogen bond while maintaining the properties of
      the interface. This technique allowed us to correlate various properties of the
      hydrogen bond directly with the difference in the PAs between both partners: it
      is possible to tune the potential energy surface of the bonding hydrogen atom
      from that of an ordinary hydrogen bond (localized hydrogen atom) to that of a low
      barrier hydrogen bond (LBHB, delocalized hydrogen atom) just by varying the
      proton affinity of one partner. This correlation shows clearly that matching PAs
      are of lesser importance for the formation of a LBHB than the relative energy
      difference between the two tautomers of the hydrogen bond.

PMID- 17186074
TI  - Adsorption properties and vibrational spectra of propyne adsorbed on Rh(111).
      Comparison with other (111) metal surfaces.
AB  - We have studied the adsorption properties of propyne on the Rh(111) surface by
      means of the generalized gradient approach of density functional theory using
      periodic slab models. The simulation of the vibrational spectra has permitted us
      to corroborate and complete the experimental band assignment and to confirm the
      adsorption site preference. Propyne prefers to sit on a 3-fold hollow site, with
      the C[triple bond]C axis parallel to a Rh-Rh bond and the molecular plane tilted
      away from the surface normal. The comparison between the adsorption behaviour of
      propyne on Rh(111) and on other (111) metal surfaces allows one to provide an
      explanation for the different reactivity observed experimentally.

PMID- 17186075
TI  - [Precautions in the care of patients hospitalized with H5N1 avian influenza].
AB  - Several agencies have proposed infection control guidelines for management of
      patients admitted with the diagnosis of avian influenza. These guidelines aim to
      prevent transmission from the patient to hospital personnel and other inpatients.
      The guidelines presented here by the Advisory Committee of Nosocomial Infections
      have been elaborated for the local medical community after reviewing currently
      available recommendations. Key recommendations include admission to an isolation
      ward, cohorting of confirmed cases, hand hygiene with antiseptic solutions, use
      of N95 type masks, non-sterile disposable gloves and eye protection equipment
      during examination or when performing aerosols-generating procedures. Use of
      patient-exclusive clinical instruments, daily disinfection of the hospital ward,
      implementation of measures to reduce risk of needle stick injuries and eye
      splashing, and reinforcement of appropriate sampling and transport of blood and
      other corporal fluids, are also recommended.

PMID- 17186076
TI  - [Influenza associated excess mortality in Argentina: 1992-2002].
AB  - OBJECTIVE: To describe the effect of influenza on mortality in Argentina, from
      1992 to 2002. METHOD: In order to fulfill this objective, influenza associated
      excess mortality was determined by the application of ARIMA method to mortality
      data for pneumonia and influenza and for all causes. RESULTS: Excess mortality
      was only detected during subtype A/H3N2 seasons. The model yielded about 31,240
      excess mortality for all causes. Pneumonia deaths contributed in about 15%.
      Approximately 80-95% of pneumonia and influenza excess mortality was restricted
      to persons > 64 years old. CONCLUSIONS: These estimations show that the virus
      circulation has had an important influence on mortality, increasing the number of
      deaths, especially in elderly population. The aging of the population reinforces
      the need of preventing strategies, including vaccination programs with high
      coverage in elderly population.

PMID- 17186077
TI  - [Imipenem-cilastatin use in a university hospital in Chile].
AB  - Imipenem is an expensive broad-spectrum antimicrobial, reserved for infections
      caused by multi-resistant nosocomial pathogens. Since 2001 our university
      hospital applies a restriction policy that allows rejecting or authorizing its
      use after a supervising evaluation with pre-specified criteria for appropriate or
      inappropriate use. An audit was performed for all the supervisions made during
      the periods of March-April and September-October, 2004, totalling 136 treatments.
      In global terms, 58.1% of treatments were considered appropriate and 11.8%
      inappropriate; other 20.6% had been discontinued by physicians in charge prior to
      evaluation. Susceptibility to other antimicrobials compounds was the main reason
      for inappropriate use. The remaining fraction involved deceased or discharged
      patients. Discontinuation of treatments by supervising physicians allowed to save
      75 days and 362 vials of imipenem equivalent to US $ 6,777 during this period
      after discounting administrative and human resources costs.

PMID- 17186079
TI  - [Epidemiology of HIV infection and acquired immune deficiency disease syndrome in
      Chile].
AB  - Since 1984 to December 2004, 14.611 HIV/AIDS cases (85% in males) have been
      reported to the Chilean surveillance system. This figure represents an incidence
      of 103 x 10(5) inhabitants. The epidemic affects mainly men in their active
      working and sexual age. The main risk factor for infection, has been the sexual
      contact. Universal access to antiretroviral therapy (ART) has changed the
      epidemic trend. In 1997 bi-therapy and in 2003 three-drug therapy (HAART) were
      implemented. Mortality was 2,4 cases x 10(5) inhabitants during 2004, with a 67%
      reduction since 1984. Vertical transmission has been significantly reduced, as a
      result of implementing since 1995 a preventive strategy that benefits
      seropositive women and their newborn infant. Local experts are preparing an
      electronic registration system in order to optimize resources and to accede to
      statistics in a real time.

PMID- 17186078
TI  - [High relationship between ciprofloxacin use and prevalence of ESBL Klebsiella
      pneumoniae].
AB  - BACKGROUND: To assess the relationship between ciprofloxacin use and the
      prevalence of extended spectrum betalactamases (ESBL) Klebsiella pneumoniae.
      PATIENTS AND METHODS: Semestral mean values regarding use of antibiotic and
      prevalence of ESBL Kp were compared during 9 semesters using linear regression
      and coefficient of correlation. RESULTS: The only statistically significant
      correlation was ciprofloxacin use and ESBL(+) K. pneumoniae prevalence, with a
      coefficient of correlation of 0.86 and p = 0.0027 using linear regression.
      CONCLUSIONS: Ciprofloxacin use must be taking into account when considering
      infection control programs due to high prevalence rates of ESBL(+) K. pneumoniae
      in the hospital setting.

PMID- 17186080
TI  - [Cryptococcus neoformans arthritis in elderly adult: case report and review].
AB  - Cryptococcal infection is not frequent in immunocompetent patients. The most
      commonly involved sites are the lungs and the central nervous system.
      Cryptococcal osteomyelitis occurs in 5-10% of patients with disseminated
      cryptococcosis with few reports of cryptococcal arthritis in elderly adults. We
      describe the case of a 92-year-old woman with a Cryptococcus neoformans knee
      joint infection associated to osteomyelitis.

PMID- 17186081
TI  - [Bacteraemia due to Campylobacter fetus in an immune suppressed patient].
AB  - We report a case of bacteraemia by Campylobacter fetus subsp. fetus in a 77 year
      old woman with immunosuppression secondary to steroid use. Diagnosis was
      suspected by finding Gram negative curved rods in blood cultures taken after 4
      days of a febrile illness without local findings. Diarrhea was not present. There
      was no consumption of undercooked meat or non-pasteurized milk and no contact
      with pets. The patient was treated with sulbactam-cefoperazone due to the
      coexistence of urinary tract infection by multiresistant E. coli. The outcome was
      favorable and albeit susceptibility was not assessed, quinolone resistance was
      presumed because illness appeared during ciprofloxacin prophylaxis for urinary
      tract infection. In contrast to C. jejuni infections, C. fetus infections are
      associated to debilitated or immunosuppressed patients, bacteraemia is
      predominant, diarrhea is rarely observed and disease is not self-limited.

PMID- 17186082
TI  - [Leuconostoc infections in patients with short gut syndrome, parenteral nutrition
      and continuous enteral feeding].
AB  - Leuconostoc is a gram-positive cocci, quite ubiquitous in nature. It is used in
      wine industry, and for aroma and texture of dairy products. Occasionally it has
      been isolated from humans in cases of bacteremia, catheter associated infections,
      sepsis, meningitis, pneumonia, UTI, osteomyelitis and hepatic dysfunction. Short
      bowel syndrome, patients with CVC and patients with gastrostomy undergoing
      enteral feeding, are described amongst the factors associated with this
      infection. The isolation of a gram-positive cocci, that does not hydrolyze
      arginine and that is resistant to vancomycin leads to this diagnostic
      possibility. Antibiotic treatment: penicillin or ampicillin.

PMID- 17186083
TI  - [Neonatal meningitis caused by atypical Streptococcus pneumoniae: case report and
      review].
AB  - Streptococcus pneumoniae is a rarely recognized cause of neonatal sepsis and/or
      meningitis, but it is associated with substantial morbidity and mortality.
      Traditionally, S. pneumoniae is identified in the laboratory by demonstrating
      susceptibility to optochin. However, the emergence of optochin-resistant
      organisms makes definite identification difficult when only phenotypic tests are
      taken as markers. We present the case of a severe early-onset neonatal meningitis
      due to an atypical strain of S. pneumoniae. Laboratory methods utilized to
      certify this species diagnosis are discussed.

PMID- 17186084
TI  - [Brucellosis in a student].
AB  - We describe the case of a student with a history of two and a half months of
      fever, hepatosplenomegaly, cutaneous, hematological and bone manifestations,
      within an epidemiological background compatible with the diagnosis of
      Brucellosis. Diagnosis of Brucella abortus was confirmed by serology and positive
      blood cultures. Clinical manifestations of brucellosis and diagnostic and
      treatment strategies are reviewed.

PMID- 17186085
TI  - [Nocardia asteroides].

PMID- 17186086
TI  - [A contribution to historical understanding of brucellosis in Chile].

PMID- 17186087
TI  - [Centennary of Albert B. Sabin MD birthdate].

PMID- 17186088
TI  - [Serological study for Chagas disease in children younger than 10 years old from
      Valparaiso and San Antonio, Chile].

PMID- 17186089
TI  - [The philosophy of being an internist].

PMID- 17186090
TI  - [Microsatellite instability among patients with colorectal cancer].
AB  - BACKGROUND: In patients with colorectal carcinoma, insertions or deletions of
      short sequences of DNA, a phenomenon called microsatellite instability, are
      observed. AIM: To look for microsatellite instability and mutations of MLH1 and
      MSH2 gene mutations in patients with colorectal carcinoma. MATERIAL AND METHODS:
      Ten patients with sporadic colorectal carcinoma and 31 patients fulfilling
      criteria for hereditary nonpolyposis colon cancer (HNPCC), aged 9 to 70 years,
      were studied. Microsatellite instability was studied in samples of tumor and
      peripheral blood mononuclear cell DNA. Six markers were amplified by polymerase
      chain reaction and capillary electrophoresis. In samples with microsatellite
      instability, mutations of MLH1 and MSH2 genes were studied by direct sequencing.
      RESULTS: Thirty four percent of patients had microsatellite instability and among
      these, 76% had a high degree of instability. BAT40 marker had the higher
      frequency of instability. No mutations for MLH1 and MSH2 genes were observed.
      However a new polymorphism, C399T, was identified in exon 3 of MSH2 gene. This
      polymorphism was observed both in patients with sporadic colorectal carcinoma and
      patients with HNPCC. CONCLUSIONS: There is a high frequency of microsatellite
      instability among patients with colorectal cancer. A new polymorphism, not
      previously reported, was identified in MSH2 gene.

PMID- 17186091
TI  - [First finding of Chagas disease vectors associated with wild bushes in the
      Metropolitan Region of Chile].
AB  - BACKGROUND: Insects of the subfamily triatominae are the biological vectors of
      Trypanosoma cruzi, the causal agent of Chagas disease. AIM: To search for wild
      colonies of triatomines in the Metropolitan Region of Chile. MATERIAL AND
      METHODS: Ad hoc traps were placed in two endemic zones of the Metropolitan Region
      of Chile, during 30 nights. The dejections of 16 T infestans and 43 M spinolai
      specimens were examined under the microscope, searching for live metacyclic
      trypomastigotes. A polymerase chain reaction (PCR) was performed in macerates of
      all insects looking for T cruzi DNA. RESULTS: A total of 269 bugs were captured.
      Forty four were Triatoma infestans and 225 were Mepraia spinolai. They were not
      syntopic, since T infestans was restricted to a Southern zone (Calera de Tango)
      while M spinolai was only found in the Northern zone (Til-Til). Both species were
      found associated to terrestrial bromeliads (Puya sp) but M spinolai was also
      detected in stony grounds. Microscopic examination of dejections yielded a
      trypano-triatomine index of 56.3 and 32.6 for T infestans and M spinolai,
      respectively. PCR detected T cruzi DNA in 41 and 43% of T infestans and M
      spinolai specimens, respectively. CONCLUSIONS: The finding of T infestans in a
      wild habitat is noticeable. This is the first report of such phenomenon in Chile.
      The high infection rates with T cruzi, explains the maintenance of Chagas disease
      wild cycle in Chile.

PMID- 17186092
TI  - [Gallbladder polyps: correlation between ultrasonographic and histopathological
      findings].
AB  - BACKGROUND: Gallbladder polyps are becoming a common finding. The management of
      these polyps is complicated considering that they can bear malignant lesions.
      AIM: To analyze the ultrasonographic and histopathologic findings of patients
      operated due to gallbladder polyps. PATIENTS AND METHODS: The records of patients
      with ultrasonographic diagnosis of gallbladder polyp and that underwent
      cholecystectomy in a thirteen years period were reviewed, collecting their
      demographic, ultrasonographic and histopathological data. RESULTS: One hundred
      and twenty three patients were operated. The mean age was 44+/-13 years, and 69%
      were women. The mean size of polyps in ultrasonography was 7.3+/-5 mm.
      Histopathology confirmed the presence of polyps in 79% of patients, with a mean
      size and number of lesions of 5.1+/-3.8 mm and 2.1+/-2, respectively. Nine
      percent of polyps were greater than 10 mm, and single polyps were significantly
      larger than the multiple ones (p =0.003). Four cases of adenoma (3.2%) were
      diagnosed; one of them had in situ carcinoma. All were single and larger than 10
      mm. We found a significant correlation between ultrasonographic and
      histopathological polyp size determination (r =0.47; p =0.002). Polyp size was
      also a predictor of the presence of adenoma (p =0.043; confidence intervals:
      1.006-1.424). CONCLUSIONS: There is a good correlation between the size of the
      gallbladder polyp in ultrasonography and the size in the histopathology report.
      Gallbladder adenoma is uncommon and it correlates with the size of the polyp. In
      this series, size was the only predictor of the presence of adenoma.

PMID- 17186093
TI  - [Cat-scratch disease. Review of eight adult patients hospitalized for fever or
      adenopathy].
AB  - BACKGROUND: Cat-scratch disease is common among children. Among adults the
      disease is less often considered in the differential diagnosis of enlarged lymph
      nodes and fever. AIM: To report the clinical and laboratory features of eight
      patients with cat-scratch disease. MATERIAL AND METHODS: Review of the medical
      records of eight patients (aged 22 to 57 years, six males) with a serological
      diagnosis of cat-scratch disease (an IgG titer over 1:256, by
      immunofluorescence). RESULTS: Only five patients recalled having had contact with
      cats. Seven had fever and weight loss. Six had excessive sweating and five had
      chills. Seven had painfully enlarged lymph nodes mainly in submandibular and
      axillary regions. All had an increased C reactive protein and six had elevated
      erythrocyte sedimentation rate. Five had leukocytosis and four an elevated serum
      lactate dehydrogenase. The disease subsided in all, even in one patient that did
      not receive antimicrobials. CONCLUSIONS: Cat-scratch disease should be considered
      in the differential diagnosis of adult patients with lymph adenitis and fever.

PMID- 17186094
TI  - [Usefulness of thrombolytic therapy with low doses of streptokinase in acute
      myocardial infarction].
AB  - BACKGROUND: The optimal dose of Streptokinase in the treatment of acute
      myocardial infarction is not well established. Apparently, the thrombolytic
      efficacy would not increase with doses over 750,000 units. AIM: To compare the
      effectiveness and safety of treatment with low doses of Streptokinase, ranging
      from 500,000 to 750,000 units, in patients with ST elevation acute myocardial
      infarction. PATIENTS AND METHODS: From September 1993 to September 1998, the GEMI
      register of patients with acute myocardial infarction, was carried out in 37
      hospitals, incorporating 4,938 patients. Of these, 1,631 patients received
      streptokinase. According to the administered dose of Streptokinase, patients were
      divided in two groups: 1,465 patients who received 1.5 millions U in 60 minutes
      (classical therapy group), and 166 patients with ischemic chest discomfort and
      either ST-segment elevation or left bundle-branch block on the electrocardiogram,
      who received 500,000 to 750,000 U streptokinase administered in no more than 30
      minutes, with heparin, within 0 to 6 hours of symptom onset. Successful
      reperfusion, mortality, complications, and hospital outcome was evaluated in both
      groups. RESULTS: The low dose group of patients had a better reperfusion criteria
      profile. No differences between groups were observed in patient evolution,
      mortality, maximum Killip classification, post myocardial infarction heart
      failure, ischemic complications, arrhythmias or mechanical complications.
      CONCLUSIONS: These results suggest that streptokinase in low doses is at least as
      effective as classical therapy, in the treatment of ST elevation acute myocardial
      infarction.

PMID- 17186095
TI  - [Type 1 diabetes mellitus incidence in Santiago, Chile. Analysis by counties in
      the period 2000-2004].
AB  - BACKGROUND: There are great geographical differences in the incidence of type I
      diabetes mellitus. AIM: To determine the incidence rate of type 1 diabetes
      mellitus (DM1) in the Metropolitan Region of Santiago, Chile from January 1, 2000
      to December 31, 2004 and to observe the distribution of cases in the different
      counties of Santiago. MATERIAL AND METHODS: All the cases diagnosed with DM1 in
      the Metropolitan Region who fulfilled the following requirements were included in
      the study: age of onset <15 years, insulin treatment from onset, permanent
      residency in the area, and a diagnosis made between January, 2000 and December,
      2004. RESULTS: The incidence of DM1 was 6.58/100,000 inhabitants/year, and showed
      a significant increase from 2001 to 2004 (5.44 and 8.33 inhabitants/year,
      respectively, p <0.04). The incidence of DM1 also increased significantly in
      children younger than 4 years old. The incidence by counties exhibited large
      differences, ranging from 1.5 to 26.6/100,000 inhabitants. Counties with higher
      income, urbanization and low aborigine component showed a high incidence rate of
      type 1 diabetes. CONCLUSIONS: In the Metropolitan Region of Santiago, an increase
      of the incidence of DM1 has occurred in the period 2000-2004, especially in
      children younger than 4 years old. Large differences among counties were
      observed.

PMID- 17186096
TI  - [Endovascular repair of abdominal aortic aneurysm. Results in 80 consecutive
      patients].
AB  - BACKGROUND: Endovascular repair of abdominal aortic aneurysms (AAA) avoids
      laparotomy, shortens hospital stay and reduces morbidity and mortality related to
      surgical repair, allowing full patient recovery in less time. AIM: To report
      short and long term results of endovascular repair of AAA in 80 consecutive
      patients treated at our institution. PATIENTS AND METHODS: Between September 1997
      and February 2005, three women and 77 men with a mean age 73.6+/-7.7 years with
      AAA 5.8+/-1.0 cm in diameter, were treated. The surgical risk of 38% of patients
      was grade III according to the American Society of Anesthesiologists
      classification. Each procedure was performed in the operating room, under local
      or regional anesthesia, with the aid of digital substraction angiography. The
      endograft was deployed through the femoral artery (83.7% bifurcated, 16.3%
      tubular graft). A femoro-femoral bypass was required in 11.3% of cases. Follow-up
      included a spiral CT scan at 1, 6 and 12 months postoperatively, and then
      annually. RESULTS: Endovascular repair was successfully completed in 79/80
      patients (98.7% technical success). The procedures lasted 147+/-71 min. Length of
      stay in the observation unit was 20.6+/-13.5 h. Blood transfusion was required in
      10%. Sixty two percent of the patients were discharged before 72 h. One patient
      died 8 days after surgery due to a myocardial infarction (1.3%). During follow-up
      (3-90 months), 1 patient developed late AAA enlargement due to a type I endoleak,
      requiring a new endograft. No AAA rupture was observed. Survival at 4 years was
      84.2% (SE =9.2). Endovascular re-intervention free survival was 82.7% (SE =9.5).
      CONCLUSION: Endovascular surgery allows effective exclusion of AAA avoiding
      progressive enlargement and/or rupture and is a good alternative to open repair.
      Close and frequent postoperative follow up is mandatory.

PMID- 17186097
TI  - [Smoking and chronic obstructive pulmonary disease: attributable risk
      determination].
AB  - BACKGROUND: Smoking is the main risk factor for Chronic Obstructive Pulmonary
      Disease (COPD), an important cause of morbidity and mortality. AIM: To estimate
      smoking attributable risk and population attributable risk in COPD patients
      attended in Public Health Services of Santiago. MATERIALS AND METHODS: A case
      control study matched by sex and age was carried out. Crude and adjusted
      attributable risks as well as population attributable risk were estimated,
      controlled by potential confounders and by interaction variables. RESULTS: Mean
      ages for cases and controls were 68 and 67 years respectively. When compared to
      the control group, COPD patients had a higher smoking prevalence (at least 100
      cigarettes in their life span: 89.7% vs 60.3%; p <0.01). Among COPD patients,
      heavy smokers proportion was 4 times higher than in controls, they smoked for
      more years (43 vs 31; p <0.01) and more cigarettes per day (18 vs 5; p <0.01).
      Adjusted attributable risk was 87% (95% Confidence Interval (CI): 63.7-94.8). If
      a patient smoked at least 100 cigarettes in his/her life span and this risk was
      92.7% (CI: 82.4-96.9) for heavy smokers. Projecting this index to Santiago
      inhabitants, about 87,000 individuals older than 40 years would be suffering COPD
      due to smoking. CONCLUSIONS: This article confirms the strong association between
      smoking and COPD. Attributable risks are high and significant, even when they are
      adjusted by confounding variables. Women had a higher risk than men, at lower
      levels of tobacco consumption.

PMID- 17186098
TI  - [Diagnosis of bone lesions using image guided percutaneous biopsy].
AB  - BACKGROUND: Percutaneous biopsies have a good sensitivity and specificity for the
      diagnosis of bone lesions. AIM: To report the experience with 270 percutaneous
      bone lesions biopsies guided with fluoroscopy or computed tomography. MATERIAL
      AND METHODS: Retrospective review of the medical records of 270 patients (mean
      age 53.4 years, range 4 to 95 years; 134 female) subjected to a percutaneous
      biopsy of a bone lesion, guided either by computed tomography or fluoroscopy. The
      final analysis included the tumor type, tumor malignancy, tumor grade and
      complications of the procedure. RESULTS: One hundred seventy nine lesions were
      malignant and 91 benign. Of the malignant lesions, 95 were metastatic and 84 were
      primary. In 3 cases, the initial diagnosis was a false negative (1.1%). Only one
      patient had a local hematoma after the procedure. CONCLUSIONS: Image guided
      percutaneous biopsy of bone lesions is a safe, effective, fast and economic
      procedure to obtain a pathological diagnosis of bone lesions.

PMID- 17186099
TI  - [Effects of the implementation of Universal Access with Explicit Guaranties
      (AUGE) Plan on the quality of care of patients with terminal renal failure].
AB  - BACKGROUND: The implementation of the AUGE plan for renal failure in Chile in
      August 2002, generated larger waiting list for outpatient care. AIM: To analyze
      the incidence of terminal renal failure, the proportion of patients that were
      admitted to hemodialysis using a definitive vascular access and the lapse of use
      of transitory catheters, before and after the implementation of AUGE in Calama.
      MATERIAL AND METHODS: Since 1999, in a dialysis center of Calama, all new
      patients that are admitted to hemodialysis and the type of vascular access they
      have are registered. Using this registry, the incidence of terminal renal failure
      and the lapse between the admission to the center and the installation of a
      definitive vascular access were calculated for the period 2000 to 2005. RESULTS:
      From January 2000 to December 2003, the incidence of terminal renal failure was
      stable in 190 +/- 21 patients per million inhabitants (ppmh). It decreased
      between January and September 2004 to 124 +/- 18.6. Afterwards, it progressively
      increased to 221 +/- 21 ppmh. In the study period, the proportion of patients
      admitted to hemodialysis with a definitive access decreased from 63 to 10%
      (p<0.01) and the mean lapse of transitory catheter use, increased from 32.9 +/-
      42.6 to 73.1 +/- 80.4 days (p<0.01). CONCLUSIONS: The implementation of AUGE for
      chronic renal failure reduced the quality of care of patients admitted to
      hemodialysis.

PMID- 17186100
TI  - [Prevalence of microtia and anotia at the maternity of the University of Chile
      Clinical Hospital].
AB  - BACKGROUND: Microtia is a congenital defect characterized by disturbances in the
      size and form of the ear lobe. Anotia corresponds to the absence of the ear lobe.
      AIM: To study the prevalence of microtia and anotia at the Maternity of the
      University of Chile Clinical Hospital. MATERIAL AND METHODS: Analysis of the
      database of the Latin American Collaborative Study of Congenital Defects
      (ECLAMC). All newborns and stillborns with congenital defects are incorporated to
      this database. RESULTS: The prevalence of microtia-anotia in the period 1982-2001
      was 8.7 per 10,000 born alive. Chilean hospitals have an uniform prevalence of
      5.2 per 10,000 born alive. Thirty seven percent presented as isolated
      malformations and the rest were associated to other defects. Eighty six percent
      of non isolated cases were part of a syndrome. Sixty eight percent were mild or
      moderate forms and the rest, severe forms. Two cases were stillborns and two
      newborns died before hospital discharge. CONCLUSIONS: The prevalence of microtia
      in this hospital and in the rest of Chilean hospitals is significantly higher
      than in the rest of non Chilean hospitals participating in the ECLAMC, that is
      4.1 per 10,000 born alive.

PMID- 17186101
TI  - [Relationship between post-traumatic stress disorder, child sexual abuse and
      sexual re-victimization].
AB  - There is a relationship between child sexual abuse and adult psychopathology. We
      report a 35 year-old woman derived to the Psychiatric Service of the Curico
      Hospital due to anxiety and depressive symptoms lasting eight years, to
      illustrate the above mentioned relationship. At the psychiatric unit, a post
      traumatic stress disorder of belated onset, triggered by sexual abuse during
      childhood, re-edited after her daughter's birth, was diagnosed. This case
      illustrates different factors, which, in retrospective studies, have been
      associated with the morbid consequences of child sexual abuse, and allows an
      understanding of how different sexually traumatic events, during a person's
      lifetime, contribute to the development of a psychopathology. The problem was
      confronted by the mental health team at different levels and symptoms subsided in
      few interventions. An active search of the traumatic sexual background, allowed
      this achievement. The importance of studying and validating clinical situations
      as the present case, with methodologies based on evidence, is stressed.

PMID- 17186102
TI  - [Multiple carcinoid tumors of the small bowel. Report of one case].
AB  - Small bowel carcinoid tumors are more common in the distal ileum and they are
      multiple in 30% of cases. The most common clinical manifestation is abdominal
      pain and the treatment of choice is surgical excision. We report a 63 years old
      female consulting for abdominal pain. An intestinal transit by computed axial
      tomography revealed multiple images compatible with small bowel carcinoid tumors.
      She had a surgical excision of the involved intestinal segment and the
      pathological study confirmed the imaging diagnosis. In the follow up, this
      patients has been asymptomatic.

PMID- 17186103
TI  - [Inflammatory reconstitution immune syndrome associated to antiretroviral therapy
      and meningeal cryptococcosis].
AB  - The objective of high activity antiretroviral therapy (HAART) in patients with
      AIDS, is to obtain immune restoration. This means a reduction of the viral load
      and restitution of the CD4 cell count. A decreased rate of HIV replication
      improves both the number and function of CD4 cells. Nevertheless, this treatment
      sometimes results in the reappearance of previous symptoms from treated
      conditions due to opportunistic infections (ie: tuberculosis, criptococcosis,
      hepatitis, Pneumocystis jirovesi, toxoplasmosis, etc) or non infectious condition
      such as sarcoidosis, Graves disease or Kaposi sarcoma. This is known as
      Inflammatory Reconstitution Immune Syndrome (IRIS). We report a 37 year-old woman
      in stage C3-AIDS with a previous criptococcal meningitis. She was treated,
      achieving a marked improvement with treatment and subsequent suppressive therapy
      with fluconazole 200 mg/day. IRIS appeared after 8 months of ongoing
      antiretroviral therapy with immune restoration with the development of aseptic
      meningitis and intracranial hypertension. The opportunistic agent could not be
      identified by cultures. Additional laboratory tests excluded toxoplasmosis,
      tuberculosis, bacterial cerebral abscesses, syphilitic cerebral gummas, and
      lymphoma. Brain CT and magnetic resonance studies were compatible with brain
      vasculitis and leptomeningitis. The patient condition improved with general
      measures, such as a repeated lumbar punctures and non steroidal anti-inflammatory
      drugs. We conclude that this patient had an IRIS due to a Cryptococcus neoformans
      antigen.

PMID- 17186104
TI  - [Accidental ingestion of magnets in children. Report of three cases].
AB  - Accidental ingestion of foreign bodies in childhood is an increasing problem.
      Although many of them can be treated with an expectant approach, allowing their
      passage through the gastrointestinal tract, magnets must be extracted, due to
      their high rate of complications, such as perforation. We report three patients
      that ingested magnets. A five year-old male was operated with an extensive
      ulceration of the jejunum, where a cylindrical magnet was extracted. A four year
      old female was operated with a perforation of the anterior wall of the stomach
      and three magnets were extracted from the peritoneal cavity. A four year-old
      female, was transferred from a hospital where she had been operated for a magnet
      ingestion that provoked three perforations in the small bowel.

PMID- 17186105
TI  - [Definition of Internal Medicine, Internist, Mission and Vision of Sociedad
      Medica de Santiago (Chilean Society of Internal Medicine). Document issued by the
      Governing Board].

PMID- 17186106
TI  - [Tattooing and piercing in teenagers].
AB  - The presence of mutilations in the form of tattooing and body piercing is
      becoming increasingly common in adolescents, a practice that is not free of risk.
      Reported complications include local infections, bleeding, tearing,
      hypersensitivity reactions, transfusion-transmitted diseases (hepatitis B virus,
      hepatitis C virus, HIV, syphilis), Chagas' disease and infective endocarditis. On
      the other hand, several studies have demonstrated an association between body
      modifications and high-risk behavior in adolescents, as alcohol or drug abuse,
      cigarette smoking, violence and schooling problems. There is also an association
      with depression, suicide, eating disorders and other psychophysiologic disorders.
      This is a review of body modifications in adolescents, emphasizing in the risks,
      complications and motivations of this practice.

PMID- 17186107
TI  - [Circulatory mechanical support. State of the art].
AB  - Despite advances in medical treatment, the prognosis of advanced heart failure
      remains poor. The number of hospitalizations for heart failure exacerbations
      continues to increase and most patients will ultimately die of complications
      related to heart failure. Implantable left ventricular assist devices (LVAD) are
      currently in use throughout the world with increasing frequency. This paper is a
      comprehensive review about mechanical support, focusing on a general description
      of the different LVAD, complications and mortality.

PMID- 17186108
TI  - [What is Internal Medicine?].
AB  - Internal Medicine can be defined as a medical specialty devoted to the
      comprehensive care of adult patients, focused in the diagnosis and non surgical
      treatment of diseases affecting internal organs and systems (excluding gyneco
      obstetrical problems) and the prevention of those diseases. This position paper
      reviews the history of Internal Medicine, the birth of its subspecialties and the
      difficulties faced by young physicians when they decide whether to practice as
      internist or in a subspecialty. In Chile as in most occidental countries formal
      training in a subspecialty of internal medicine requires previous certification
      in internal medicine but the proportion of young physicians who remain in
      practice as general internists appears to be considerably lower than those who
      choose a subspecialty. The main reasons for this unbalance can be related to
      financial advantages (by the practice of specialized technologies) and the
      patients' tendency to request direct assistance by a professional thought to be
      better qualified to take care of their specific problems. Training programs in
      internal medicine should consider a greater emphasis in comprehensive outpatient
      care instead of the traditional emphasis for training in hospital wards.

PMID- 17186111
TI  - The question of a right to life in animal ethics.
AB  - In animal ethics a Right to Life has been postulated repeatedly, but no valid
      argument has been produced yet. Thus the question of a Right to Life in animal
      ethics remains unanswered. It is remarkable that no philosopher has yet found a
      valid argument against Epicurus (there is nothing fearful in the absence of
      life). On the other hand, there is, again based upon Epicurus' argument, a basic
      moral duty with respect to painless killing (i.e. no fear, no distress, no
      suffering).

PMID- 17186110
TI  - [Perception independent of interest: a contribution to the relationship between
      people and animals].
AB  - In occidental cultures the relation of humans to animals is determined by the
      human perception of the outer world. Using motives from evolutionary epistemology
      it is argued that the evolutionary pressure to adapt increasingly obscures
      perception, where perception means relating to the outer world in a way that is
      independent of interests. Therefore, the pressure to adapt and to realise the
      interest to adapt obscures perception. This results in a reduced self-perception.
      Two phenomena exemplify this: persons ignoring their own bodies and a reductive
      perception relating to animals, such as reducing the value of animals to mere
      human resources. This reductive perception explains the very limited success of
      the animal rights-debate.

PMID- 17186112
TI  - Animals have a right to life.
AB  - State and church must be separated; therefore the legal and the judicial system
      may not be based on religious dogmas but instead must be grounded on empirical
      rational ethics, which are amenable to consensus. To achieve this, consciousness
      must be described in scientific terms and the anthropocentric view of animals as
      fundamentally different to humans must be criticised on a factual basis. It turns
      out that consciousness determines autonomy. And consciousness is an evolutionary
      continuity, meaning that there is no basic difference in consciousness between
      humans and animals. Life is of the utmost instrumental value to autonomous
      beings, as it enables them to realise their autonomy and is thus in their highest
      interests. In contrast, killing is the greatest harm that can be done to such
      beings. As I, being an autonomous being, want to act autonomously, I demand a
      right to life from society to do so. The principle of universality compels me to
      demand the same right for every other autonomous being.

PMID- 17186113
TI  - Genetically modified laboratory animals in the name of the 3Rs?
AB  - Although the introduction of GM animal models at first was viewed as a potent way
      to enhance experimental biology in the name of the 3Rs by its proponents, over
      the years, the number of animals used has greatly increased and concerns about
      the suffering of these animals have emerged in the debate. The purpose of this
      contribution is to show the need and the urgency for a systematic evaluation of
      genetically modified laboratory animals (GM animals) according to the 3Rs
      principle. This evaluation presents various difficulties due to the special
      features of the genetic modifications of animals, the variety of scientific
      purposes connected with the use of these animals, the lack of coherent
      statistical data about this use and the difficulties related to the welfare
      assessment of these animals. In this article I discuss the significance of the
      procedures involving GM animals for each of the 3R principles. On this basis, I
      offer an answer to the question of whether these procedures are compatible with
      the spirit of the 3Rs.

PMID- 17186114
TI  - Intrathoracic cancer of the splenic flexure.
AB  - Blunt traumatic rupture of the diaphragm is a well known but uncommon event of
      thoracoabdominal traumatic injuries. It occurs in 1-5% of polytrauma patients and
      requires a high degree of suspicion for a rapid diagnosis. The frequency of
      delayed diagnosis is difficult to be estimated and up to 30% of blunt
      diaphragmatic ruptures present late. A case of herniated splenic colic flexure
      through a defect in the left hemidiaphragm and the subsequent development of
      colon cancer in this area are presented. We emphasize the importance of making a
      prompt diagnosis in order to avoid further morbidity and mortality in this rare
      clinical entity.

PMID- 17186115
TI  - Ganciclovir-resistant, cytomegalic interstitial lung disease in a patient with
      systemic lupus erythematosus.
AB  - A patient with systemic lupus erythematosus developed interstitial lung disease
      initially felt to be a manifestation of the disease but that, on further workup,
      proved to be a manifestation of cytomegalic disease resistant to ganciclovir.
      Treatment with foscarnet was associated with prompt improvement.

PMID- 17186116
TI  - Ankylosing spondylitis is linked to Klebsiella--the evidence.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory spinal and large-joint
      arthritic and potentially disabling condition, mainly affecting males of young
      age groups. Extensive literature based on the results of various genetic,
      microbiological, molecular and immunological studies carried out by independent
      research groups suggests that Klebsiella pneumoniae is the main microbial agent
      being implicated as a triggering and/or perpetuating factor in the
      etiopathogenesis of AS. Novel diagnostic markers and criteria based on the
      association with high anti-Klebsiella antibodies could be used in the detection
      of AS patients during early stages of the disease, and together with the current
      treatments might help in implementing the use of new therapeutic anti-microbial
      measures in the management of AS. Prospective longitudinal studies with the use
      of anti-microbial measures in patients with AS are required to establish the
      therapeutic benefit of this microbe-disease association.

PMID- 17186118
TI  - Annual growth of invasive Larix kaempferi seedlings with reference to
      microhabitat and ectomycorrhizal colonization on a volcano.
AB  - To investigate the seedling growth of a biologically invasive larch Larix
      kaempferi (Lamb.) Carr. on Mount Koma, Japan, seedlings were excavated from three
      microhabitats (bareground = BA, Salix reinii patch = SP, and Larix understory =
      LU) in three elevational zones. Seedlings showed the highest ectomycorrhizal
      (ECM) colonization percentage in the most shaded microhabitat, LU. ECM
      colonization percentages in BA and SP were found to decrease with decreasing
      elevation. These results inferred that the ECM colonization percentages were
      related to seedling growth, particularly in BA and SP. However, the annual
      seedling growth was not synchronized with the increases in either elevational
      gradients. Although ECM colonization was most evident in LU, the seedling growth
      was the lowest. We concluded that the effects of ECM colonization on seedling
      growth were reduced mostly by microhabitat characteristics.

PMID- 17186117
TI  - Infection-related morbidity and mortality in patients with connective tissue
      diseases: a systematic review.
AB  - Patients suffering from connective tissue diseases (CTDs) constitute an important
      subgroup of immunosuppressed patients at risk for developing serious infections.
      Prophylactic antibiotic administration may decrease infection-related morbidity
      and mortality burden in patients with CTD, though one needs first to evaluate the
      overall effect of infection on morbidity and mortality in such patients and the
      presence of adequate prognostic/risk factors for infection development. Studies
      focusing on infection-related morbidity and mortality in patients with CTD were
      reviewed. Data on disease type, therapeutic regimens used, including
      corticosteroid dose and method of administration as well as other
      immunosuppressive agents, and outcome were extracted to evaluate the existence of
      specific treatment patterns predisposing to infection as well as infectious
      disease-related morbidity and mortality in patients with CTD. Thirty-nine studies
      focusing on infection incidence and/or outcome in patients with CTD were
      identified and analyzed; the majority of the reviewed studies (20) included
      patients with systemic lupus erythematosus (SLE). The mortality attributed to
      infection was 5.2%, while the overall mortality was 20%. There were no adequate
      data on the specific effect patterns of corticosteroid and immunosuppressant
      treatment on infection risk. Pneumocystis jiroveci (carinii) pneumonia, evaluated
      independently, exhibited significant mortality in patients with Wegener's
      granulomatosis, polymyositis/dermatomyositis, and SLE. In conclusion, infectious
      diseases are a major cause of mortality in patients with CTD. However, treatment
      related factors predisposing to serious infections have not been adequately
      outlined. In addition, there are no data regarding the effect of prophylactic
      practices involving antibiotic administration in morbidity and mortality.

PMID- 17186119
TI  - The WiscDsLox T-DNA collection: an arabidopsis community resource generated by
      using an improved high-throughput T-DNA sequencing pipeline.
AB  - We have developed a new community resource, called the WiscDsLox collection, for
      performing reverse-genetic analysis in arabidopsis. This resource is composed of
      10,459 T-DNA lines generated using the Arabidopsis thaliana ecotype Columbia. The
      flanking sequence tag for each T-DNA insertion has been deposited in public
      databases, and seed for each line is currently available from the Arabidopsis
      Biological Resource Center. The pDsLox vector used to create this new population
      contains a Ds transposon and Cre/Lox recombination sites. Each WiscDsLox line
      therefore has the potential to serve as a launch-pad for performing local
      saturation mutagenesis by mobilization of the Ds element. In addition, Cre-Lox
      recombination between the T-DNA and a transposed Ds element should enable
      targeted deletion of specific genomic regions. We generated the WiscDsLox
      collection using an improved high-throughput pipeline that streamlines analysis
      of large numbers of independent Arabidopsis thaliana (L.) Hyenh. lines. In this
      paper we describe the details of this novel method and also provide potential
      users of WiscDsLox T-DNA lines with useful background information about this
      collection. Experiments to characterize the utility of the Ds transposon and
      Cre/Lox elements present in the WiscDsLox lines are in progress and will be
      reported in the future.

PMID- 17186121
TI  - Supplementary analyses regarding Langevin, Langevin, and Curnoe's (2007) findings
      on fraternal birth order in homosexual men.
AB  - A recent article by Langevin, Langevin, and Curnoe (2007) reported mixed results
      regarding the fraternal birth order effect, that is, the repeatedly observed
      finding that older brothers correlate with homosexuality in later-born males.
      Using a fraternal birth order index computed as older brothers minus younger
      brothers, Langevin et al. found that the "homoerotic" probands were born later
      among their brothers than were the "heteroerotic" probands in their full sample
      (N = 1194) and in their subsample over age 19 (N = 1122), but not in their
      subsample over age 31 (N = 698) or in their subsample with mothers over age 46 at
      the proband's birth (N = 727). The present writer concluded that the results
      obtained with the larger samples are more reliable, based on analyses
      demonstrating that (1) the larger samples are unlikely to be seriously affected
      by incomplete sibships, and (2) the smaller samples have poor statistical power.
      A separate analysis, based on an approximate reconstruction of Langevin et al.'s
      raw data, indicated that their heteroerotic probands reported a ratio of 104
      older brothers per 100 older sisters, which is close to the normative population
      value of 106, whereas their homoerotic probands reported a ratio of 137,
      indicating a statistically significant excess of older brothers. These results
      suggest that Langevin et al.'s data showed significant evidence of a fraternal
      birth order effect and that their data were consistent with previous studies of
      this phenomenon.

PMID- 17186120
TI  - Osmotic water permeability of plasma and vacuolar membranes in protoplasts I:
      high osmotic water permeability in radish (Raphanus sativus) root cells as
      measured by a new method.
AB  - Intra- and transcellular water movements in plants are regulated by the water
      permeability of the plasma membrane (PM) and vacuolar membrane (VM) in plant
      cells. In the present study, we investigated the osmotic water permeability of
      both PM (P ( f1)) and VM (P ( f2)), as well as the bulk osmotic water
      permeability of a protoplast (P ( f(bulk))) isolated from radish (Raphanus
      sativus) roots. The values of P ( f(bulk)) and P ( f2) were determined from the
      swelling/shrinking rate of protoplasts and isolated vacuoles under hypo- or
      hypertonic conditions. In order to minimize the effect of unstirred layer, we
      monitored dropping or rising protoplasts (vacuoles) in sorbitol solutions as they
      swelled or shrunk. P ( f1) was calculated from P ( f(bulk)) and P ( f2) by using
      the 'three-compartment model', which describes the theoretical relationship
      between P ( f1), P ( f2) and P ( f(bulk)) (Kuwagata and Murai-Hatano in J Plant
      Res, 2007). The time-dependent changes in the volume of protoplasts and isolated
      vacuoles fitted well to the theoretical curves, and solute permeation of PM and
      VM was able to be neglected for measuring the osmotic water permeability. High
      osmotic water permeability of more than 500 mum s(-1), indicating high activity
      of aquaporins (water channels), was observed in both PM and VM in radish root
      cells. This method has the advantage that P ( f1) and P ( f2) can be measured
      accurately in individual higher plant cells.

PMID- 17186122
TI  - Women's hedonic ratings of body odor of heterosexual and homosexual men.
AB  - Men's body odor influences women's mate choice and individual variation among
      traits affects hedonic perceptions of this odor (e.g., immune system
      characteristics). Previous research by Sergeant (2002) indicated that one such
      characteristic is sexual orientation: body odor from homosexual men was perceived
      by heterosexual women as more hedonically pleasing than that of heterosexual men.
      The current study re-examined the influence of men's sexual orientation on
      women's perceptions of body odor. Homosexual (n=10) and heterosexual (n=9) men
      produced samples of body odor using T-shirts under equivalent environmental
      conditions. Heterosexual women (n=35) rated these samples, and a set of unused T
      shirts, using a series of hedonic scales. Women rated the body odor of homosexual
      men as being comparatively more pleasant, sexier, and more preferable than that
      of heterosexual men but not significantly different from the unused T-shirts.
      This finding was consistent with contemporary research demonstrating that an
      individual's sexual orientation significantly impacts their olfactory function,
      both in terms of body odor production and olfactory perceptions of certain
      compounds.

PMID- 17186123
TI  - The use of cyberpornography by young men in Hong Kong: some psychosocial
      correlates.
AB  - This study examined the prevalence of online pornography viewing and its
      psychosocial correlates among a sample of young Chinese men in Hong Kong. A total
      of 229 participants completed a questionnaire designed to measure their online
      pornography viewing, peer and parental influences, openness to experience, and
      various types of sex-related attitudes. Results showed that online pornography
      viewing was common and was strongly associated with peer influence and
      susceptibility to peer pressure. Moreover, participants who reported to have more
      online pornography viewing were found to score higher on measures of premarital
      sexual permissiveness and proclivities toward sexual harassment. Conceptual and
      applied implications of these findings are discussed.

PMID- 17186124
TI  - Sex ratio of older siblings in heterosexual and homosexual, right-handed and non
      right-handed men.
AB  - This study investigated why older brothers, which increase the odds of
      homosexuality in later-born males who are right-handed, have no effect or the
      opposite effect on later-born males who are non-right-handed. The specific
      question was whether the different results for the non-right-handed men have to
      do with the heterosexual non-right-handers or the homosexual non-right-handers.
      The human sex ratio at birth (106 males per 100 females) was used as a gold
      standard for determining which groups differ from the general population and in
      which direction. All usable data from previous studies were combined to obtain
      the largest possible sample (N = 8,201). The observed ratio of older brothers to
      older sisters was 105 for the heterosexual right-handers, 128 for the homosexual
      right-handers, 127 for the heterosexual non-right-handers, and 96 for the
      homosexual non-right-handers. The ratios for the homosexual right-handers and the
      heterosexual non-right-handers differed significantly from the expected value.
      These results suggest that both heterosexual and homosexual non-right-handers
      contribute to the older brothers x handedness x sexual orientation interaction.

PMID- 17186125
TI  - 8-13 Hz fluctuations in rectal pressure are an objective marker of clitorally
      induced orgasm in women.
AB  - Orgasm is a subjective experience accompanied by involuntary muscle contractions.
      We hypothesized that orgasm in women would be distinguishable by frequency
      analysis of a perineal muscle-derived signal. Rectal pressure, an index of
      perineal muscle activity, was measured continuously in 23 healthy women during
      different sexual tasks: receiving clitoral stimulation, imitation of orgasm, and
      attempt to reach orgasm, in which case the women were asked to report whether
      orgasm had been reached ("orgasm") or not ("failed orgasm attempt"). We performed
      spectral analysis on the rectal pressure data and calculated the spectral power
      in the frequency bands delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and
      beta (13-25 Hz). The most significant and most important difference in spectral
      power between orgasm and both control motor tasks (imitation of orgasm and failed
      orgasm attempt) was found in the alpha band. An objective rule based on spectral
      power in the alpha band recognized 94% (29/31) of orgasms and correctly labeled
      69% (44/64) of all orgasm attempts as either successful or failed. Because
      outbursts of alpha fluctuations in rectal pressure only occurred during orgasm
      and not during voluntary imitation of orgasm or failed attempts, we propose that
      they represent involuntary contractions of muscles in the rectal vicinity. This
      is the first objective and quantitative measure that has a strong correspondence
      with the subjective experience of orgasm.

PMID- 17186126
TI  - Family size, birth order, and parental age among male paraphilics and sex
      offenders.
AB  - A sample of 1823 male paraphilics, sex offenders, and non-sex offender controls
      were compared on family size, birth order, and parents' ages at the time of the
      probands' births. Sample data were also compared to population data from
      Statistics Canada. The men in all groups were from larger than average Canadian
      families and they tended to be later born. Paraphilics and sex offenders had even
      larger families than offender controls. Their parents tended to be older at their
      birth with 34.2% of mothers and 51.3% of fathers over 30 years of age, but there
      were no statistically significant subgroup differences. There were also
      significantly more multiparous teenage mothers than expected and more
      paraphilics' fathers who were younger than the mothers, both factors associated
      in the literature with increased risk of perinatal complications and
      abnormalities. The confounding influences of parental age, birth order, and
      family size were examined and indicated the need for large samples and
      multivariate analysis in evaluating the role of family variables associated with
      paraphilics and sex offenders.

PMID- 17186127
TI  - Sex differences in memory for sexually-relevant information.
AB  - The present study was conducted in an attempt to examine potential differences
      between men and women in memory for sexually relevant information. A total of 77
      undergraduate students (31 men, 46 women) read a sexual story and completed
      memory tasks in response to the story. Based on previous research, we
      hypothesized that differences would exist between men and women for different
      types of sexual information and we hoped to understand whether specific variables
      (sexual experiences, sexual functioning, and reactions to the sexual story) could
      explain such differences. Men were more likely to remember erotic or explicit
      details of the story, whereas women were more likely to remember love and
      emotional bonding details of the story. Additionally, women were more likely to
      recall information referencing the characters in the story. Results from
      regression analyses indicated that sexual desire and satisfaction were related to
      differences in recall and recognition of the love and emotional bonding aspects
      of the story, and that frequency of sexual intercourse was related to differences
      in the recall of erotic or explicit details of the story. The significant results
      obtained in this study correspond to previously established sex differences in
      memory for sexual information.

PMID- 17186128
TI  - Sexual scripts of women: a longitudinal analysis of participants in a gender
      specific HIV/STD prevention intervention.
AB  - Project FIO (The Future Is Ours) was a three arm randomized controlled HIV
      prevention intervention trial carried out with heterosexually-active women in a
      high seroprevalence area of New York City. The trial was effective and women in
      the eight-session intervention arm were significantly more likely to report
      decreased unsafe sex or no unsafe sex compared to controls at one month and one
      year post-intervention. The current investigation was a qualitative analysis of
      women's sexual scripts at baseline and one year follow-up for a randomly selected
      subsample of participants in Project FIO. We examined the domains of sexual
      initiation, pace setting, sexual decision-making, communication about sexual
      needs, and the timing of condom introductions in the experimental and control
      arms at baseline and one year follow-up. At one year follow-up, among both the
      experimental and control arms, results showed changes away from male-dominated
      and toward female-dominated sexual initiation and sexual decision-making. Among
      both the experimental and control arms, results also showed that trial
      participants shifted from a late condom introduction (right before intercourse)
      toward much earlier mention of condoms (e.g. during a date). The fact that shifts
      in sexual scripts at one year follow-up occurred in both groups is likely
      reflective of the degree to which a lengthy assessment interview facilitated
      comfort with discussing and imagining new sexual behaviors, even for control
      group participants who did not receive the intervention. The value of empirically
      assessing sexual scripts in HIV/AIDS prevention and doing so longitudinally is
      assessed in light of the goals of HIV prevention interventions.

PMID- 17186129
TI  - The utility of the diagnosis of pedophilia: a comparison of various
      classification procedures.
AB  - This study examined the utility of the diagnosis of pedophilia in a sample of
      extra-familial child molesters assessed at a university teaching hospital between
      1982 and 1992. Pedophilia was defined in one of four ways: (1) DSM diagnosis made
      by a psychiatrist; (2) deviant phallometric profile; (3) DSM diagnosis and a
      deviant phallometric profile; and, (4) high scores based on the Screening Scale
      for Pedophilic Interest (Seto & Lalumiere, 2001). Demographic data, psychological
      tests, and offence history were obtained and group differences were analyzed
      along with the ability of certain variables to contribute uniquely to the
      classification of pedophilia. Results indicated that few significant differences
      existed on psychological measures between pedophilic and nonpedophilic extra
      familial child molesters regardless of the classification system employed.
      Finally, results indicated that the procedures used to define pedophilia were not
      significantly related to one another. Results are discussed in terms of the
      utility of the diagnosis of pedophilia.

PMID- 17186130
TI  - Sexual and relationship functioning in men with chronic prostatitis/chronic
      pelvic pain syndrome and their partners.
AB  - This study compared the sexual and relationship functioning of 38 male patients
      with Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) to that of their
      female partners, and of both the men and women in these couples to those in 37
      control couples. Male sexual function was also examined as a predictor of partner
      sexual function. In comparison to control males, the men with CP/CPPS reported
      significantly more sexual dysfunction and symptoms of depression. Furthermore,
      symptoms of depression mediated the relationship between some aspects of sexual
      function and male participant status as a patient or control. However, men with
      CP/CPPS did not report significantly decreased sexual satisfaction or
      relationship functioning compared to controls. Partners of men with CP/CPPS
      reported significantly more pain upon intercourse, vaginismus, and depressive
      symptoms when compared to control females. In addition, patients with CP/CPPS and
      their partners did not differ significantly from each other with regard to sexual
      functioning and satisfaction, relationship functioning, and symptoms of
      depression. Patient sexual functioning significantly predicted female partner
      sexual functioning. This study was the first to evaluate partners of men with
      CP/CPPS. Patients and partners in this study reported lower levels of sexual
      functioning in some domains, yet were comparable to control couples on measures
      of satisfaction and relationship functioning. Furthermore, the sexual and
      relationship functioning of patients and partners was significantly associated.
      The results of this study have implications for the assessment and management of
      CP/CPPS and for future research in this area.

PMID- 17186132
TI  - Childhood sexual abuse and adult sexual dysfunction: response to commentary by
      Rind and Tromovitch (2007).
AB  - Rind and Tromovitch (2007) raised four concerns relating to our article (Najman,
      Dunne, Purdie, Boyle, & Coxeter, 2005. Archives of Sexual Behavior, 34, 517-526.)
      which suggested a causal association between childhood sexual abuse (CSA) and
      adult sexual dysfunction. We consider each of these concerns: magnitude of
      effect, cause and effect, confounding, and measurement error. We suggest that,
      while the concerns they raise represent legitimate reservations about the
      validity of our findings, on balance the available evidence indicates an
      association between CSA and sexual dysfunction that is of "moderate" magnitude,
      probably causal, and unlikely to be a consequence of confounding or measurement
      error.

PMID- 17186131
TI  - Gene-environment contributions to young adult sexual partnering.
AB  - To date, there has been relatively little work on gene-environment contributions
      to human sexuality, especially molecular analyses examining the potential
      contributions of specific polymorphisms in conjunction with life experiences.
      Using Wave III data from 717 heterozygous young adult sibling pairs included in
      the National Longitudinal Study of Adolescent Health, this article examined the
      combined contributions of attendance at religious services and three genetic
      polymorphisms (in the dopamine D4 receptor [DRD4]), dopamine D2 receptor [DRD2]),
      and the serotonin transporter promoter [5HTT]) to sensation seeking, a
      personality construct related to sexual behavior, and the number of vaginal sex
      partners participants had in the year before interview. Data analyses used an
      Allison mixed model approach to account for population stratification and
      correlated observations. DRD4 was unrelated to sensation seeking and to the
      number of sex partners in tests of both main effects and in interaction with
      religious attendance. Contrary to hypothesis, presence of the A1 DRD2 allele was
      associated with having had fewer sex partners in the past year. Associations
      between the 5HTT allele and sex partners varied by religious attendance, but
      again the patterns of associations were contrary to hypothesized relationships
      and were small in magnitude. These findings underscore the necessity of using
      more comprehensive multiple gene-multiple life experience approaches to
      investigations of complex behaviors such as sexual patterns.

PMID- 17186133
TI  - In situ dark field microscopy for on-line monitoring of yeast cultures.
AB  - A new-type in situ probe has been developed to acquire dark field images of yeast
      in bioreactors. It has been derived from an in situ bright field microscope that
      is able to measure cell density in bioreactors during fermentation processes. The
      illumination part of the probe has been replaced with a dark field device, in
      which an aspheric condenser is used, so that high contrast dark field images can
      be obtained. The technique of second imaging is implemented to improve the
      sharpness of the images by means of a relay lens. This new in situ probe is
      expected to enable the evaluation of the cell viability without staining owing to
      modern image processing.

PMID- 17186135
TI  - Myocardial calcification and subendocardial fatty replacement of the left
      ventricle following myocardial infarction.
AB  - We report a 70 years old man with old myocardial infarction of the anteroseptal
      wall. He had an acute anterior myocardial infarction ten years ago and coronary
      angiography showed a total occlusion of the left middle anterior descending
      coronary artery. He underwent a multidetector cardiac computed tomography for
      rule out another coronary stenosis before the surgery of a postrenal aortic
      aneurysm. The unenhanced computed tomography image realized for the
      quantification of the coronary calcium reveals a low-attenuation curvilinear
      stripe consistent with subendocardial fat at the anterior ventricular wall and a
      curvilinear focal apical left ventricular calcification. In this case without a
      precontrast CT the subendocardial fat could have been misinterpreted , leading us
      to conclude that a hypoenhancement area (perfusion defect) secondary from the
      reduced delivery of contrast in the subendocardium was present. The presence of
      calcium in the myocardium can make not trustworthy the estimation of the size of
      the infarct and the presence or absence of viability in the same one especially
      when it is realized by means of magnetic resonance.

PMID- 17186134
TI  - Carotid artery intima media thickness, plaque and Framingham cardiovascular score
      in Asia, Africa/Middle East and Latin America: the PARC-AALA study.
AB  - OBJECTIVE: The PARC-AALA (Paroi arterielle et Risque Cardiovasculaire in Asia
      Africa/ Middle East and Latin America) study was designed to evaluate the
      correlation between intima-media thickness of the common carotid artery (CCAIMT),
      carotid plaque and absolute cardiovascular risk in a multi-ethnic population.
      METHODS: An international, cross-sectional, study including 79 centres from 21
      countries in Asia, Africa, the Middle East and Latin America. Two thousand three
      hundred and twenty-eight subjects, meeting all inclusion criteria, were
      stratified by risk factors groups (no modifiable factor or at least both
      uncontrolled hypertension and hypercholesterolemia). CCAIMT, presence of plaque
      and cardiovascular risk factors were assessed for each individual. RESULTS: Some
      intergeographical characteristics in demographics, and risk factors were found
      accompanying early atherosclerosis marker differences. In Asia where the subjects
      were at lower risk, the mean CCAIMT was 4% lower than in Africa/Middle East and
      Latin America. On multiple linear regression analysis CCAIMT and carotid plaque
      were independently associated with increased Framingham cardiovascular score
      (FCS) without heterogeneity across geographic regions. CCAIMT and carotid plaque
      explained roughly 20% of the FCS in both genders. CONCLUSION: The PARC-AALA study
      confirms the correlation between CCAIMT and FCS in three different populations.
      Intima-media thickness (IMT) and plaque evaluation may represent a complementary
      predictive tool for detection of cardiovascular disease in individuals.

PMID- 17186136
TI  - Ethical considerations in CT angiography.
AB  - The rapid development and clinical deployment of CT angiography raises several
      important issues, including assurance of professional competence and technical
      quality, self-referral, the relative role of radiologists and cardiologists,
      appropriateness and proper indications, the detection and disposition of
      unexpected or incidental findings and the concern for the rapidly increasing
      costs of health care and imaging. These questions are properly addressed within
      the framework of medical ethics, including principles of beneficence, autonomy
      and justice.

PMID- 17186137
TI  - The relationship between the level of plasma B-type natriuretic peptide and
      mitral stenosis.
AB  - B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are both
      secreted primarily from the ventricle myocardium in response to the increase in
      volume and pressure. We aimed to investigate the relationship between the
      severity of mitral stenosis (MS) and the level of plasma BNP. A total of 56
      patients (50 female, 6 male) were included in the study. Mitral stenosis and its
      related parameters were evaluated by echocardiographic methods. Patients were
      divided into three groups as with mild, moderate and severe MS according to their
      planimetric valvular area. Plasma BNP levels were measured using "Triage-B-type
      natriuretic peptide test" method (Biosite Diagnostics, San Diego). The
      relationship of BNP with mitral stenosis and other echocardiographic parameters
      were studied. The comparison of the 3 groups with one another revealed that the
      BNP level in the group with moderate MS was higher than that in the group with
      mild MS, however it was statistically insignificant (74.9 +/- 49.7 versus 49.9 +/
      40.5 pg/ml, p > 0.05). BNP level in the group with severe MS was significantly
      higher than that in the mild MS (144.3 +/- 83.9 versus 49.9 +/- 40.5 pg/ml, p <
      0.001) and that in the moderate MS group (144.3 +/- 83.9 versus. 74.9 +/- 49.7
      pg/ml, p < 0.05). When patients were taken together, as the area of the mitral
      valve decreased, the level of BNP underwent a corresponding increase (r:-0.48, p
      < 0.001). We have ascertained that the level of plasma BNP and the degree of MS
      are significantly correlated, and as MS becomes more serious, the plasma BNP
      level rises.

PMID- 17186138
TI  - A practical guide to reading CT coronary angiograms--how to avoid mistakes when
      assessing for coronary stenoses.
AB  - There are now many physicians, both radiologists and cardiologists who are
      reporting CT coronary angiography (CTCA) scans who may not be aware that there
      are many pitfalls present. For the inexperienced reader a significant stenosis in
      a coronary artery can be easily missed or a moderate stenosis overcalled as
      significant. Artifacts can also be misinterpreted as representing a significant
      lesion. It is important that the studies are correctly interpreted, especially as
      the reported high negative predictive value of CTCA scans is a major strength of
      this imaging technique. The learning curve of reading these scans is steep and
      access to conventional coronary catheterisation results is essential for feedback
      and to improve the readers results. We have developed some rules to aid beginners
      avoid some of the pitfalls that can occur as these studies are not as easy to
      read as they may appear initially.

PMID- 17186139
TI  - Detection of occult medullary thyroid cancer recurrence with 2-deoxy-2-[F
      18]fluoro-D-glucose-PET and PET/CT.
AB  - PURPOSE: 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography
      (PET) has an established role in restaging of various cancers, including
      papillary and undifferentiated thyroid carcinoma. However, controversies exist
      regarding its ability to reliably assess recurrent medullary thyroid cancer
      (MTC). We were therefore prompted to review our experience with FDG-PET for
      detection of occult MTC. METHODS: This is a retrospective study (Apr 1, 1997-Mar
      31, 2004) of 13 patients with histologic diagnosis of MTC, who had PET
      examinations. The group included six men and seven women, 15-62 years old
      (average: 48+/-13). The PET scan request was triggered by rising levels of
      calcitonin and negative anatomical imaging studies. RESULTS: Recurrent/metastatic
      disease was identified by PET in seven (54%) of the 13 patients. The lesions were
      located in superior mediastinum (4), cervical lymph nodes (3), thyroid bed (2),
      lung (1) and liver (1). The calcitonin levels ranged from 52 to 5,090 pg/ml
      (average: 1,996 pg/ml) in patients with negative PET scans and from 132 to 9,500
      pg/ml (average: 3,757 pg/ml) in patients with positive studies. The sensitivity
      and specificity of FDG-PET for disease detection in this cohort were 85.7% (95%
      CI: 48.7-97.4) and 83.3% (95% CI: 43.6-96.9), respectively. CONCLUSION: Our
      findings suggest a significant role for FDG-PET in patients with suspected MTC
      recurrence, with sensitivity of 85.7% and specificity of 83.3% for disease
      detection. FDG-PET provides additional information in a significant fraction of
      cases (54%) and could be used for restaging of patients with MTC and elevated
      levels of biomarkers (calcitonin). Additional studies are necessary to further
      evaluate the role of FDG-PET in MTC.

PMID- 17186140
TI  - Protection of oilseed rape (Brassica napus) toward fungal pathogens by strains of
      plant-associated Bacillus amyloliquefaciens.
AB  - In this report, four Bacillus strains were tested for effects on plant fitness
      and disease protection of oilseed rape (Brassica napus). The strains belonged to
      newly discovered plant-associated Bacillus amyloliquefaciens and a recently
      proposed species, Bacillus endophyticus. The fungal pathogens tested represented
      different infection strategies and included Alternaria brassicae, Botrytis
      cinerea, Leptosphaeria maculans, and Verticillium longisporum. The B.
      amyloliquefaciens strains showed no or a weak plant growth promoting activity,
      whereas the B. endophyticus strain had negative effects on the plant as revealed
      by phenological analysis. On the other hand, two of the B. amyloliquefaciens
      strains conferred protection of oilseed rape toward all pathogens tested. In
      vitro experiments studying the effects of Bacillus exudates on fungal growth
      showed clear growth inhibition in several but not all cases. The protective
      effects of Bacillus can therefore, at least in part, be explained by production
      of antibiotic substances, but other mechanisms must also be involved probably as
      a result of intricate plant-bacteria interaction. The protective effects observed
      for certain Bacillus strains make them highly interesting for further studies as
      biocontrol agents in Brassica cultivation.

PMID- 17186141
TI  - Adaptation of salt-tolerant Myxococcus strains and their motility systems to the
      ocean conditions.
AB  - More and more studies have indicated that myxobacteria are able to live in
      seawater conditions, which, however, can decrease the fruiting body formation
      ability and also the adventurous (A) and social (S) motility systems of the
      myxobacteria. To learn the adaptation mechanism of the salt-tolerant myxobacteria
      to marine conditions, we analyzed 10 salt-tolerant Myxococcus strains of their
      fruiting body formation and motility. The isolates were from marine samples and
      possessed different levels of salt tolerance. They had the dual motility system
      and formed fruiting bodies in the presence of suitable seawater concentrations.
      Some high salt-tolerant strains even lost their fruiting abilities in the absence
      of seawater. In response to the presence of seawater, the S-motility was found to
      be increased in the high salt-tolerants but decreased in the low salt-tolerants.
      The A-motility, on the other hand, was observed in all the salt-tolerant
      Myxococcus strains, but increased or decreased in response to the presence of
      seawater. Perceived shifts of fruiting body formation abilities and motilities
      discovered in the salt-tolerant Myxococcus strains suggested an ecological
      adaptation of myxobacterial social behaviors to the marine environments.

PMID- 17186142
TI  - Molecular monitoring of microbial population dynamics during operational periods
      of anaerobic hybrid reactor treating cassava starch wastewater.
AB  - This study characterized the microbial community and population dynamics in an
      anaerobic hybrid reactor (AHR) treating cassava starch wastewater. Methanogens
      and nonmethanogens were followed during the start-up and operation of the
      reactor, and linked to operational and performance data. Biomass samples taken
      from the sludge bed and packed bed zones of the AHR at intervals throughout the
      operational period were examined by 16S rRNA fluorescence in situ hybridization
      (FISH). The start-up seed and the reactor biomass were sampled during the feeding
      of the wastewater with a chemical oxygen demand (COD) value of 8 g L(-1) and a
      hydraulic retention time (HRT) of 8 days. These samples were characterized by the
      predominance of cells with long-rod morphology similar to Methanosaeta spp.
      Following a sharp operational change, accomplished by increasing the COD
      concentration of the organic influent from 8 to 10 g L(-1) and reducing the HRT
      from 8 to 5 days, there was a doubling of the organic loading rate, a reduction
      of the COD removal efficiency, as well as decreased methane content in the biogas
      and an accumulation of total volatile acids in the reactor. Moreover, this
      operational change resulted in a significant population shift from long-rod
      Methanosaeta-like cells to tetrad-forming Methanosarcina-like cells. The
      distributions of microbial populations involved in different zones of the AHR
      were determined. The results showed that nonmethanogens became the predominant
      population in both sludge and the packed bed zone. However, the percentage of
      methanogens in the packed bed zone was higher than that in the sludge bed zone.
      This higher percentage of methanogens was likely caused by the fact that the
      packed bed zone provided a suitable environmental condition with an appropriate
      nutrient availability for methanogen growth.

PMID- 17186143
TI  - Rhizosphere-bacterial community in Eperua falcata (Caesalpiniaceae) a putative
      nitrogen-fixing tree from French Guiana rainforest.
AB  - The rainforest of French Guiana is still largely unaffected by human activity.
      Various pristine sites like the Paracou Research Station are devoted to study
      this tropical ecosystem. We used culture-independent techniques, like polymerase
      chain reaction-temperature gradient gel electrophoresis, and construction of
      clone libraries of partial 16S rRNA and nifH genes, to analyze the composition of
      the bacterial community in the rhizosphere of mature trees of Eperua falcata and
      Dicorynia guianensis, both species within the Caesalpiniaceae family. E. falcata
      is one of the more abundant pioneer tree species in this ecosystem and so far, no
      root nodules have ever been found. However, its nitrogen-fixing status is
      regarded as "uncertain", whereas D. guianensis is clearly considered a non
      nitrogen-fixing plant. The rhizospheres of these mature trees contain specific
      bacterial communities, including several currently found uncultured
      microorganisms. In these communities, there are putative nitrogen-fixing bacteria
      specifically associated to each tree: D. guianensis harbors several Rhizobium
      spp. and E. falcata members of the genera Burkholderia and Bradyrhizobium. In
      addition, nifH sequences in the rhizosphere of the latter tree were very diverse.
      Retrieved sequences were related to bacteria belonging to the alpha-, beta-, and
      gamma-Proteobacteria in the E. falcata rhizoplane, whereas only two sequences
      related to gamma-Proteobacteria were found in D. guianensis. Differences in the
      bacterial communities and the abundance and diversity of nifH sequences in E.
      falcata rhizosphere suggest that this tree could obtain nitrogen through a
      nonnodulating bacterial interaction.

PMID- 17186144
TI  - Cloning of environmental genomic fragments as physical markers for monitoring
      microbial populations in coking wastewater treatment system.
AB  - The association between community functional shift and dynamics of genomic DNA
      composition can be used to identify functionally relevant populations as
      indicator organisms for systems monitoring. In this work, fingerprinting-based
      community DNA hybridization was used to monitor community structural dynamics and
      identify genomic fragments whose abundance shifts were concomitant to changes in
      COD removal capacity in a reactor. A laboratory-scale anaerobic-anoxic-oxic fixed
      biofilm system treating coking wastewater was operated with (LR mode) or without
      effluent recirculation (LNR mode). The contribution to total chemical oxygen
      demand (COD) removal by the anoxic reactor increased from 4% in LNR mode to 26%
      in LR mode. Long primer RAPD (randomly amplified polymorphic DNA) community
      fingerprints of the anoxic reactor also changed most significantly from the one
      similar to the anaerobic reactor to one similar to the oxic reactor. DNA
      hybridization revealed one signature band of 2.1 kb shared by the anoxic and oxic
      reactors in LR, but not LNR mode. Clone library profiling of this band resulted
      in one predominant 2.1-kb genomic fragment (B3) with no homologous sequences in
      GenBank. Real-time polymerase chain reaction indicated that copy numbers of B3 in
      the anoxic reactor under LR mode were 69 times higher than that under LNR mode,
      concomitant to a significant increase in COD removal capacity in this reactor.
      The different patterns of distribution of B3 in the laboratory system and a
      comparable malfunctioning industrial system demonstrated the potential of this
      genomic fragment as physical markers in systems monitoring. In addition, this
      genomic fragment may allow sequence-guided isolation of the host microbe.

PMID- 17186145
TI  - Ciliates are the dominant grazers on pico- and nanoplankton in a shallow,
      naturally highly eutrophic lake.
AB  - Abundance and biomass of the microbial loop members [bacteria, heterotrophic
      nanoflagellates (HNF), and ciliates] were seasonally measured in the naturally
      eutrophic and shallow (2.8 mean depth) Lake Vortsjarv, which has a large open
      surface area (average 270 km2) and highly turbid water (Secchi depth <1 m).
      Grazing rates (filter feeding rates) on 0.5-, 3-, and 6-microm-diameter particles
      were measured to estimate pico- and nanoplankton grazing (filter feeding) by
      micro- and metazooplankton. Among grazers, HNF had a low abundance (<50 cells mL
      1) and, due to their low specific filtering rates, they only grazed a minor
      fraction of the bacterioplankton (<or=4.2% of total grazing). Ciliates were
      relatively abundant (<or=158 cells mL-1) and, considering their high specific
      feeding rates, were able to graze more than 100% of the bacterial biomass
      production in the open part of the lake, whereas the average daily grazing
      accounted for 9.3% of the bacterial standing stock. Ciliates were potentially
      important grazers of nanoplanktonic organisms (on average, approximately 20% of
      the standing stock of 3-microm-size particles was grazed daily). Metazooplankton
      grazed a minor part of the bacterioplankton, accounting for only 0.1% of standing
      stock of bacteria. Grazing on nanoplankton (3-6 microm) by metazooplankton was
      higher (0.4% of standing stock). The hypothesis is proposed that ciliates
      dominate due to a lack of top-down regulation by predators, and HNF have a low
      abundance due to strong grazing pressure by ciliates.

PMID- 17186146
TI  - Bacterial community structure of biofilms on artificial surfaces in an estuary.
AB  - This study examined bacterial community structure of biofilms on stainless steel
      and polycarbonate in seawater from the Delaware Bay. Free-living bacteria in the
      surrounding seawater were compared to the attached bacteria during the first few
      weeks of biofilm growth. Surfaces exposed to seawater were analyzed by using 16S
      rDNA libraries, fluorescence in situ hybridization (FISH), and denaturing
      gradient gel electrophoresis (DGGE). Community structure of the free-living
      bacterial community was different from that of the attached bacteria according to
      FISH and DGGE. In particular, alpha-proteobacteria dominated the attached
      communities. Libraries of 16S rRNA genes revealed that representatives of the
      Rhodobacterales clade were the most abundant members of biofilm communities.
      Changes in community structure during biofilm growth were also examined by DGGE
      analysis. We hypothesized that bacterial communities on dissimilar surfaces would
      initially differ and become more similar over time. In contrast, the compositions
      of stainless steel and polycarbonate biofilms were initially the same, but
      differed after about 1 week of biofilm growth. These data suggest that the
      relationship between surface properties and biofilm community structure changes
      as biofilms grow on surfaces such as stainless steel and polycarbonate in
      estuarine water.

PMID- 17186147
TI  - Role of marine cyanobacteria in trace metal bioavailability in seawater.
AB  - In seawater, several trace metals with biological significance are highly
      complexed with organic matter. Marine cyanobacteria are an important
      phytoplanktonic group, with the ability to release trace metal-binding compounds
      to the seawater medium, which in turn modulates their bioavailability and
      influences their biogeochemical cycles. Such interactions may allow cyanobacteria
      to more easily access less available trace metals essential for their metabolic
      processes, or, conversely, keep the toxic forms of the trace metals from reaching
      intolerable levels. In this minireview, Cu and Fe interactions with cyanobacteria
      received special attention, although other trace metals (Co, Pb, Zn, and Cd) are
      also covered. Recent research has shed light on many aspects of trace metal
      cyanobacteria ecology in seawater; nevertheless, the biochemical processes behind
      this dynamics and the structure of the vast majority of the metal binding
      compounds remain unclear.

PMID- 17186148
TI  - High-level resistance to cobalt and nickel but probably no transenvelope efflux:
      Metal resistance in the Cuban Serratia marcescens strain C-1.
AB  - Molecular mechanisms underlying inducible cobalt and nickel resistance of a
      bacterial strain isolated from a Cuban serpentine deposit were investigated. This
      strain C-1 was assigned to Serratia marcescens by 16S rDNA analysis and DNA/DNA
      hybridization. Genes involved in metal resistance were identified by transposon
      mutagenesis followed by selection for cobalt- and nickel-sensitive derivatives.
      The transposon insertion causing the highest decrease in metal resistance was
      located in the ncrABC determinant. The predicted NcrA product was a NreB ortholog
      of the major facilitator protein superfamily and central for cobalt/nickel
      resistance in S. marcescens strain C-1. NcrA also mediated metal resistance in
      Escherichia coli and caused decreased accumulation of Co(II) and Ni(II) in this
      heterologous host. NcrB may be a regulatory protein. NcrC was a protein of the
      nickel-cobalt transport (NiCoT) protein family and necessary for full metal
      resistance in E. coli, but only when NcrA was also present. Without NcrA, NcrC
      caused a slight decrease in metal resistance and mediated increased accumulation
      of Ni(II) and Co(II). Because the cytoplasmic metal concentration can be assumed
      to be the result of a flow equilibrium of uptake and efflux processes, this
      interplay between metal uptake system NcrC and metal efflux system NcrA may
      contribute to nickel and cobalt resistance in this bacterium.

PMID- 17186149
TI  - Diversity of phytases in the rumen.
AB  - Examples of a new class of phytase related to protein tyrosine phosphatases (PTP)
      were recently isolated from several anaerobic bacteria from the rumen of cattle.
      In this study, the diversity of PTP-like phytase gene sequences in the rumen was
      surveyed by using the polymerase chain reaction (PCR). Two sets of degenerate
      primers were used to amplify sequences from rumen fluid total community DNA and
      genomic DNA from nine bacterial isolates. Four novel PTP-like phytase sequences
      were retrieved from rumen fluid, whereas all nine of the anaerobic bacterial
      isolates investigated in this work contained PTP-like phytase sequences. One
      isolate, Selenomonas lacticifex, contained two distinct PTP-like phytase
      sequences, suggesting that multiple phytate hydrolyzing enzymes are present in
      this bacterium. The degenerate primer and PCR conditions described here, as well
      as novel sequences obtained in this study, will provide a valuable resource for
      future studies on this new class of phytase. The observed diversity of microbial
      phytases in the rumen may account for the ability of ruminants to derive a
      significant proportion of their phosphorus requirements from phytate.

PMID- 17186151
TI  - Low nitrification rates in acid Scots pine forest soils are due to pH-related
      factors.
AB  - In a previous study, ammonia-oxidizing bacteria (AOB)-like sequences were
      detected in the fragmentation layer of acid Scots pine (Pinus sylvestris L.)
      forest soils (pH 2.9-3.4) with high nitrification rates (>11.0 microg g-1 dry
      soil week-1), but were not detected in soils with low nitrification rates (<0.5
      microg g-1 dry soil week-1). In the present study, we investigated whether this
      low nitrification rate has a biotic cause (complete absence of AOB) or an abiotic
      cause (unfavorable environmental conditions). Therefore, two soils strongly
      differing in net nitrification were compared: one soil with a low nitrification
      rate (location Schoorl) and another soil with a high nitrification rate (location
      Wekerom) were subjected to liming and/or ammonium amendment treatments.
      Nitrification was assessed by analysis of dynamics in NH4+-N and NO3- -N
      concentrations, whereas the presence and composition of AOB communities were
      assessed by polymerase chain reaction-denaturing gradient gel electrophoresis and
      sequencing of the ammonia monooxygenase (amoA) gene. Liming, rather than ammonium
      amendment, stimulated the growth of AOB and their nitrifying activity in Schoorl
      soil. The retrieved amoA sequences from limed (without and with N amendment)
      Schoorl and Wekerom soils exclusively belong to Nitrosospira cluster 2. Our study
      suggests that low nitrification rates in acidic Scots pine forest soils are due
      to pH-related factors. Nitrosospira cluster 2 detected in these soils is
      presumably a urease-positive cluster type of AOB.

PMID- 17186153
TI  - Culturable microbial diversity and the impact of tourism in Kartchner Caverns,
      Arizona.
AB  - Kartchner Caverns in Benson, AZ, was opened for tourism in 1999 after a careful
      development protocol that was designed to maintain predevelopment conditions. As
      a part of an ongoing effort to determine the impact of humans on this limestone
      cave, samples were collected from cave rock surfaces along the cave trail
      traveled daily by tour groups (200,000 visitors year-1) and compared to samples
      taken from areas designated as having medium (30-40 visitors year-1) and low (2-3
      visitors year-1) levels of human exposure. Samples were also taken from
      fiberglass moldings installed during cave development. Culturable bacteria were
      recovered from these samples and 90 unique isolates were identified by using 16S
      rRNA polymerase chain reaction and sequencing. Diversity generally decreased as
      human impact increased leading to the isolation of 32, 27, and 22 strains from
      the low, medium, and high impact areas, respectively. The degree of human impact
      was also reflected in the phylogeny of the isolates recovered. Although most
      isolates fell into one of three phyla: Actinobacteria, Firmicutes, or
      Proteobacteria, the Proteobacteria were most abundant along the cave trail (77%
      of the isolates), while Firmicutes predominated in the low (66%) and medium (52%)
      impact areas. Although the abundance of Proteobacteria along the cave trail seems
      to include microbes of environmental rather than of anthropogenic origin, it is
      likely that their presence is a consequence of increased organic matter
      availability due to lint and other organics brought in by cave visitors.
      Monitoring of the cave is still in progress to determine whether these bacterial
      community changes may impact the future development of cave formations.

PMID- 17186150
TI  - Microbial community succession in an unvegetated, recently deglaciated soil.
AB  - Primary succession is a fundamental process in macroecosystems; however, if and
      how soil development influences microbial community structure is poorly
      understood. Thus, we investigated changes in the bacterial community along a
      chronosequence of three unvegetated, early successional soils ( approximately 20
      year age gradient) from a receding glacier in southeastern Peru using molecular
      phylogenetic techniques. We found that evenness, phylogenetic diversity, and the
      number of phylotypes were lowest in the youngest soils, increased in the
      intermediate aged soils, and plateaued in the oldest soils. This increase in
      diversity was commensurate with an increase in the number of sequences related to
      common soil bacteria in the older soils, including members of the divisions
      Acidobacteria, Bacteroidetes, and Verrucomicrobia. Sequences related to the
      Comamonadaceae clade of the Betaproteobacteria were dominant in the youngest
      soil, decreased in abundance in the intermediate age soil, and were not detected
      in the oldest soil. These sequences are closely related to culturable
      heterotrophs from rock and ice environments, suggesting that they originated from
      organisms living within or below the glacier. Sequences related to a variety of
      nitrogen (N)-fixing clades within the Cyanobacteria were abundant along the
      chronosequence, comprising 6-40% of phylotypes along the age gradient. Although
      there was no obvious change in the overall abundance of cyanobacterial sequences
      along the chronosequence, there was a dramatic shift in the abundance of specific
      cyanobacterial phylotypes, with the intermediate aged soils containing the
      greatest diversity of these sequences. Most soil biogeochemical characteristics
      showed little change along this approximately 20-year soil age gradient; however,
      soil N pools significantly increased with soil age, perhaps as a result of the
      activity of the N-fixing Cyanobacteria. Our results suggest that, like macrobial
      communities, soil microbial communities are structured by substrate age, and that
      they, too, undergo predictable changes through time.

PMID- 17186152
TI  - Prey food quality affects flagellate ingestion rates.
AB  - Flagellate feeding efficiency appears to depend on morphological characteristics
      of prey such as cell size and motility, as well as on other characteristics such
      as digestibility and cell surface characteristics. Bacteria of varying
      morphological characteristics (cell size) and mineral nutrient characteristics or
      food quality (as determined by the C:N:P ratio) were obtained by growing
      Pseudomonas fluorescens in chemostats at four dilution rates (0.03, 0.06, 0.10,
      and 0.13 h-1) and three temperatures (14 degrees C, 20 degrees C, and 28 degrees
      C). Cells of a given food quality were heat-killed and used to grow the
      flagellate Ochromonas danica. Ingestion and digestion rates were determined by
      using fluorescently labeled bacteria of the same food quality as the bacteria
      supporting growth. Ingestion rates were affected by both food quality and cell
      size. Cells of high food quality (low carbon:element ratio) were ingested at
      higher rates than cells of low food quality. Multiple regression analysis
      indicated that cell size also influenced ingestion rate but to a much lesser
      extent than did food quality. Digestion rates were not correlated with either
      food quality or cell size. Results suggest that flagellates may adjust feeding
      efficiency based on the quality of food items available.

PMID- 17186154
TI  - A nifH-based oligonucleotide microarray for functional diagnostics of nitrogen
      fixing microorganisms.
AB  - Nitrogen fixation is an important process in biogeochemical cycles exclusively
      carried out by prokaryotes, mostly by an evolutionarily conserved nitrogenase
      protein complex, of which one of the structural genes (nifH) is highly valuable
      for phylogenetic and diversity analyses. We developed a nifH-based short
      oligonucleotide microarray (nifH diagnostic microarray) as a rapid tool to
      effectively monitor nitrogen-fixing diazotrophic populations in a wide range of
      environments. Taking account of the overwhelming predominance of environmental
      nifH fragments from uncultivated microorganisms in public databases, our nifH
      microarray is mainly based on nifH sequences from as yet unidentified
      prokaryotes. Standard conditions for microarray performance were determined, and
      criteria for the design of specific oligonucleotides were defined. A primary set
      of 56 oligonucleotides was validated with fluorescence-labeled single-stranded
      nifH targets from five reference strains, 26 environmental clones, and artificial
      mixtures of reference strains. The nifH microarray was applied to analyze the
      diversity (based on DNA) and activity (based on mRNA) of diazotrophs in roots of
      wild rice samples from Namibia. Results demonstrated that only a small subset of
      diazotrophs being present in the sample were actually fixing nitrogen actively.
      Our data suggest that the developed nifH microarray is a highly reproducible and
      semiquantitative method for mapping the variability of diazotrophic diversity,
      allowing rapid comparisons of the relative abundance and activity of diazotrophic
      prokaryotes in the environment. A further refined nifH microarray comprising of
      194 oligonucleotide probes now covers more than 90% of sequences in our nifH
      database.

PMID- 17186155
TI  - Relationship between testate amoeba (protist) communities and atmospheric heavy
      metals accumulated in Barbula indica (bryophyta) in Vietnam.
AB  - We studied the relationships between testate amoeba communities and heavy metal
      (Pb, Cd, Zn, Ni, Cu, Mn, and Fe) concentrations in the moss Barbula indica
      sampled at 29 sites in and around the city of Hanoi (Vietnam). Our first approach
      was to compare the heavy metal concentrations and testate amoeba variables
      between the city (zone 1) and the surrounding (zone 2). Mean moss concentrations
      of Pb, Cd, Zn, Ni, and Cu were significantly higher and testate amoeba species
      richness and abundance were significantly lower in zone 1 and the abundance of
      eight taxa differed significantly between the two zones. We then studied the
      correlation between heavy metals and testate amoebae. Species richness and
      abundance were correlated negatively to Pb concentration. Shannon H' was
      negatively correlated to both Pb and Cd. The abundance of several species was
      negatively correlated with Pb, Cd, Zn, and Ni; however, at the community level,
      Pb emerged as the only significant variable in a redundancy analysis. Our results
      suggest that testate amoebae are sensitive to and may be good bioindicators for
      heavy metal pollution, especially lead. Further research is needed to understand
      the causal relationships underlying the observed patterns.

PMID- 17186156
TI  - Culturable and VBNC Vibrio cholerae: interactions with chironomid egg masses and
      their bacterial population.
AB  - Vibrio cholerae, the etiologic agent of cholera, is autochthonous to various
      aquatic environments. Recently, it was found that chironomid (nonbiting midges)
      egg masses serve as a reservoir for the cholera bacterium and that flying
      chironomid adults are possible windborne carriers of V. cholerae non-O1 non-O139.
      Chironomids are the most widely distributed insect in freshwater. Females deposit
      egg masses at the water's edge, and each egg mass contains eggs embedded in a
      gelatinous matrix. Hemagglutinin/protease, an extracellular enzyme of V.
      cholerae, was found to degrade chironomid egg masses and to prevent them from
      hatching. In a yearly survey, chironomid populations and the V. cholerae in their
      egg masses followed phenological succession and interaction of host-pathogen
      population dynamics. In this report, it is shown via FISH technique that most of
      the V. cholerae inhabiting the egg mass are in the viable but nonculturable
      (VBNC) state. The diversity of culturable bacteria from chironomid egg masses
      collected from two freshwater habitats was determined. In addition to V.
      cholerae, representatives of the following genera were isolated: Acinetobacter,
      Aeromonas, Klebsiella, Shewanella, Pseudomonas, Paracoccus, Exiguobacterium, and
      unidentified bacteria. Three important human pathogens, Aeromonas veronii, A.
      caviae, and A. hydrophila, were isolated from chironomid egg masses, indicating
      that chironomid egg masses may be a natural reservoir for pathogenic Aeromonas
      species in addition to V. cholerae. All isolates of V. cholerae were capable of
      degrading chironomid egg masses. This may help explain their host-pathogen
      relationship with chironomids. In contrast, almost none of the other bacteria
      that were isolated from the egg masses possessed this ability. Studying the
      interaction between chironomid egg masses, the bacteria inhabiting them, and V.
      cholerae could contribute to our understanding of the nature of the V. cholerae
      egg mass interactions.

PMID- 17186157
TI  - Occurrence and genetic structure of the systemic grass endophyte Epichloe
      festucae in fine fescue populations.
AB  - Epichloe species are systemic fungal endophytes that usually specialize in a
      certain group of related grass species. We examined the infection frequency of
      Epichloe festucae in populations of two fine fescue species (Festuca rubra and F.
      ovina) in natural and seminatural habitats at 86 study sites (total=2514 plants)
      across Finland and northern Norway. Infection incidence varied significantly
      among grass species and populations. A substantial number of the F. rubra and F.
      ovina populations (53 out of 77 and 25 out of 30, respectively) were either
      endophyte-free or had very low (<20%) infection frequencies. The highest
      infection frequencies were found in subarctic areas. Moreover, infection
      incidence differed between habitats. In the area with the highest infection
      frequencies, we used microsatellite markers to study genetic diversity and the
      rates of gene flow of E. festucae among 12 F. rubra populations. Twenty out of
      the 25 fungal genotypes detected with four microsatellite markers were carrying
      multiple alleles in at least one locus, indicating multiple infections or
      vegetative hybridization of the fungus. One dominant genotype occurred in all 12
      populations, representing 63.5% of all isolates. We found a moderate level of
      average genotypic variation and a low level of genetic differentiation
      (Fst=0.0814). There was no correlation between infection frequency and genotypic
      diversity. Although the existence of a dominant genotype and the detected linkage
      disequilibrium suggest that the fungus is mainly asexual and vertically
      transmitted, the multiallelic loci and variation of genetic diversity among
      populations indicate occasional contagious spread and sexual or parasexual
      recombination of the fungus in some populations. Furthermore, the genotypes
      carrying multiallelic loci suggest the possibility of multiple infections or
      hybridization of the endophyte.

PMID- 17186158
TI  - Phage diversity in a methanogenic digester.
AB  - It has been shown that phages are present in natural and engineered ecosystems
      and influence the structure and performance of prokaryotic communities. However,
      little has been known about phages occurring in anaerobic ecosystems, including
      those in methanogenic digesters for waste treatment. This study investigated
      phages produced in an upflow anaerobic sludge blanket methanogenic digester
      treating brewery wastes. Phage-like particles (PLPs) in the influent and effluent
      of the digester were concentrated and purified by sequential filtration and
      quantified and characterized by transmission electron microscopy (TEM),
      fluorescence assay, and field inversion gel electrophoresis (FIGE). Results
      indicate that numbers of PLPs in the effluent of the digester exceeded 1 x 10(9)
      L-1 and at least 10 times greater than those in the influent, suggesting that
      substantial amounts of PLPs were produced in the digester. A production rate of
      the PLPs was estimated at least 5.2 x 10(7) PLPs day-1 L-1. TEM and FIGE showed
      that a variety of phages were produced in the digester, including those
      affiliated with Siphoviridae, Myoviridae, and Cystoviridae.

PMID- 17186159
TI  - Sterol composition of freshwater algivorous ciliates does not resemble dietary
      composition.
AB  - Algivorous ciliates represent an important link in freshwater food webs, as they
      transfer energy and biochemical matter from their algal prey to mesozooplankton
      predators. However, it is still unknown how dietary composition influences the
      biochemical composition of ciliates. We analyzed the sterol composition of the
      algivorous ciliates Balanion planctonicum and Urotricha farcta and compared it to
      the sterol composition of their diet--the cryptomonad Cryptomonas phaseolus. The
      sterol composition of the ciliates did not resemble that of their algal diet.
      Ergosterol [(22E)-ergosta-5,7,22-trien-3beta-ol] was the sterol in highest
      concentration in C. phaseolus, whereas stigmasterol [(24S)-24-ethylcholesta-5,22E
      dien-3beta-ol] was dominant in both B. planctonicum and U. farcta. Moreover, the
      occasionally higher sterol concentrations in the ciliates than in their algal
      diet suggest sterol accumulation by the ciliates. We conclude that dietary sterol
      composition influences the composition of the two algivorous ciliates studied,
      but species-specific differences in metabolism probably determine the ultimate
      sterol composition of the ciliates.

PMID- 17186160
TI  - Influence of a random field on particle fractionation and solidification in
      liquid-crystal colloid mixtures.
AB  - The influence of a random-anisotropy (RA) type disorder on the phase separation
      of nematogen-colloid mixtures is studied theoretically by combining the
      phenomenological Landau-de Gennes, Carnahan-Starling, and hard-sphere crystal
      theories. We assume that the colloids enforce the RA disorder on the surrounding
      thermotropic liquid-crystal (LC) molecules. We adopt the Imry-Ma argument
      according to which the lower-temperature phase exhibits a domain-type pattern.
      The colloids impose a finite degree of orientational ordering even in the
      isotropic (paranematic) phase. In the ordered phase they give rise to a domain
      type structure, resulting in the distorted nematic (speronematic) phase. The RA
      field opposes the phase separation tendency. With increasing disorder the
      difference between the paranematic and speronematic ordering decreases.
      Consequently there is a critical disorder, above which both phases become
      identical from the orientation point of view, but have different concentrations
      of colloids. We have also estimated another characteristic value of disorder
      above which the isotropic phase can exist only in a liquid state, the crystal
      phase being suppressed completely.

PMID- 17186161
TI  - Growth of attached actin filaments.
AB  - In several studies of actin-based cellular motility, the barbed ends of actin
      filaments have been observed to be attached to moving obstacles. Filament growth
      in the presence of such filament-obstacle interactions is studied via Brownian
      dynamics simulations of a three-dimensional energy-based model. We find that with
      a binding energy greater than 24k B T and a highly directional force field, a
      single actin filament is able to push a small obstacle for over a second at a
      speed of half of the free filament elongation rate. These results are consistent
      with experimental observations of plastic beads in cell extracts. Calculations of
      an external force acting on a single-filament-pushed obstacle show that for
      typical in vitro free-actin concentrations, a 3pN pulling force maximizes the
      obstacle speed, while a 4pN pushing force almost stops the obstacle. Extension of
      the model to treat beads propelled by many filaments suggests that most of the
      propulsive force could be generated by attached filaments.

PMID- 17186162
TI  - Loss of beta1D-integrin function in human ischemic cardiomyopathy.
AB  - Integrins play a pivotal role in cardiomyocyte survival and function, with
      integrin loss leading to myocyte apoptosis and heart failure. The aim of this
      study was to characterize whether regulation of integrins may contribute to
      cardiac remodeling in human ischemic cardiomyopathy (ICM). Myocardial tissues of
      the left ventricle were obtained from patients with ICM (n = 8) undergoing
      cardiac transplantation and from unused donor hearts (NF, n = 8). In addition,
      tissue samples from patients with dilated cardiomyopathy (DCM, n = 5) were
      analyzed. Expression of integrins beta(1)D and beta(3), the effector proteins
      focal adhesion kinase (FAK) and melusin, and FAK phosphorylation were examined by
      Western blotting, real-time-PCR and immunofluorescence analysis, respectively.
      Beta(1)D-integrin protein was decreased in ICM vs. NF by 36%. Beta(1)D-integrin
      mRNA levels and beta(1)D-integrin shedding were unchanged. Corresponding to
      beta(1)D-integrin regulation, FAK and phosphorylated FAK were decreased in ICM
      vs. NF by 54% and 49%, respectively. beta(3)-integrin and melusin were not
      altered in ICM. As a mediator of integrin effects, AKT kinase activity was
      examined. In parallel to beta(1)D-integrin and FAK, AKT activity was decreased in
      ICM by 44%. In contrast, none of the proteins were significantly altered in DCM
      compared to NF. Integrins and integrin signaling are regulated differentially in
      ICM and DCM with a decrease of beta(1)D-integrin and FAK in ICM. The loss of the
      beta(1)Dintegrin-FAK-complex in ICM was paralleled by a reduced AKT activity
      supporting in vitro data which demonstrate the pivotal role of intact integrin
      function in anti-apoptotic signaling and cell survival.

PMID- 17186163
TI  - Intramembrane receptor-receptor interactions and volume transmission. Festschrift
      dedicated to Kjell Fuxe.

PMID- 17186166
TI  - [100 years of allergy: Clemens von Pirquet--his concept of allergy and his basic
      understanding of the disease: 2: The Pirquet concept of allergy].

PMID- 17186165
TI  - Quality of life assessment in cardiac populations.

PMID- 17186168
TI  - Traumatic kidney injury before and after reconstruction.

PMID- 17186167
TI  - [Vegetarian nutrition: preventive potential and possible risks. Part 2: animal
      foods and recommendations].
AB  - INTRODUCTION: As shown in the first part of this article, consuming high amounts
      of fruits, vegetables, whole grains and nuts can lower the risk for several
      chronic diseases. However, the relevance of animal foods consumed within a
      vegetarian diet is less well-known. MATERIALS AND METHODS: We followed a
      nutritive and a metabolic-epidemiological approach to obtain dietary
      recommendations. A MEDLINE-research was performed for all animal food groups
      relevant with a vegetarian diet (key words: "eggs", "milk", "dietary pattern"
      "vegetarian diet", "cancer", "cardiovascular disease", "diabetes mellitus",
      "osteoporosis", "vitamin D", "vitamin B(12)", "iron", "iodine"). All relevant
      food groups were characterized regarding their nutrient content and rated with
      respect to the available metabolic-epidemiological evidence. RESULTS: Based on
      the evidence criteria of the WHO/FAO, colorectal cancer risk reduction by a high
      intake of milk and milk products is assessed as probable, while a higher risk of
      prostate and ovarial carcinomas is also probable. The evidence of a risk
      increasing effect of eggs relating to cardiovascular disease, colorectal cancer
      and breast cancer is assessed as probable. As the data of prospective cohort
      studies suggest, a prudent diet pattern characterized high in fruits, vegetables,
      whole grains and nuts is associated with a lower risk of coronary heart disease
      and diabetes mellitus type 2. In contrast, there is no overall association
      between prudent diet pattern and risk of breast cancer or colorectal cancer. The
      critical key nutrients for vegetarians are vitamin D and B12, iodine and iron.
      CONCLUSION: For the first time evidence based dietary recommendations were
      provided for persons on a vegetarian diet in the D-A-CH-region.

PMID- 17186169
TI  - Clinical predictors of health-related quality of life after pacemaker
      implantation.
AB  - BACKGROUND: Health-related quality of life (HRQL) is increasingly accepted as an
      outcome measure when considering the effectiveness of therapeutic interventions.
      Little is known about the HRQL of patients with different clinical circumstances
      before and after pacemaker implantation (PMI). The purpose of this study was to
      investigate the influence of clinical symptoms and ECG diagnoses as predictors of
      improved HRQL in patients referred for PMI. METHODS: Sixty eight patients with
      different indications for PMI completed the MacNew Heart Disease Health-related
      Quality of Life Questionnaire (MacNew) and the Short Form-36 Health Survey (SF
      36) before and one, three and six months after PMI. Symptoms, ECG indications and
      pacing mode were collected using the European Pacemaker Patient Identification
      Card codes. RESULTS: Within the first month after PMI overall Mac-New but not SF
      36 scores improved significantly and was maintained during the entire 6 month
      follow up period. Improvement in HRQL as measured with the MacNew was rather
      related to baseline symptoms and ECG diagnosis than to the pacing mode.
      CONCLUSION: The important finding of this study is that improved HRQL seen after
      PMI appears to be largely driven by baseline symptoms and the ECG diagnoses
      rather than the pacing mode of the device.

PMID- 17186170
TI  - Cardiac rehabilitation in Austria: short term quality of life improvements in
      patients with heart disease.
AB  - BACKGROUND: The goal of cardiac rehabilitation programs is not only to prolong
      life, but also to improve physical functioning, symptoms, wellbeing and health
      related quality of life (HRQL). The aim of the study was to document short-term
      outcomes of cardiac rehabilitation programs in Austria. METHODS: Consecutive
      patients (N = 487, 64.7% male, age 60.9 +/- 12.5 SD years) after myocardial
      infarction (MI), with or without percutaneous interventions (PCI), coronary
      artery bypass grafting (CABG) or heart valve surgery (HVS), referred to the six
      inpatient rehabilitation centers of the Austrian PVA insurance company, were
      included in the study. Exercise capacity, risk factors and HRQL (MacNew Heart
      Disease Quality of Life Instrument [MacNew] and EuroQoL-5D [EQ-5D]) were measured
      at the beginning and end of the 4-week inpatient cardiac rehabilitation program.
      RESULTS: Global HRQL (MacNew) improved significantly over time in all patients
      combined (+0.75 +/- 0.88 SD, T = -16.99, df = 394, p < .001) and exceeded the
      minimal important difference. Patients with CABG, HVS or MI without PCI showed
      the greatest improvements in global HRQL after cardiac rehabilitation (p < .02).
      Blood pressure, cholesterol, triglyceride, body mass index, waist circumference
      improved significantly (all p < .001). CONCLUSION: These findings provide
      evidence that the improvements in HRQL and risk factors following cardiac
      rehabilitation in Austria are clinically important. HRQL should become a standard
      outcome parameter in cardiac rehabilitation.

PMID- 17186171
TI  - Seasonal variations in detecting Borrelia burgdorferi sensu lato in rodents from
      north eastern Austria.
AB  - Austria is well known as an endemic area of Lyme borreliosis. To assess the
      annual variation of rodent populations that may host agents of Lyme borreliosis
      we collected rodents in northeastern Austria. Life traps were set out every six
      weeks during a year consecutively in one each of the three different zones
      (Hohenau, Ernstbrunn, Vienna Woods) that cover the main habitat characteristics
      of small mammals in northeastern Austria. Rodents were collected and identified.
      Samples of heart, urine bladder and brain were removed under aseptic conditions
      for cultivation of borrelia. Samples of heart muscle were additionally used for
      molecular detection of borrelia by Real-Time polymerase chain reaction. PCR was
      performed with borrelia universal primers and with species-specific primers. 938
      mice were caught, most frequently Apodemus flavicollis (44%), followed by
      Clethrionomys glareolus (35%), Microtus arvalis (9%), A. sylvaticus (7%) and Mus
      musculus (6%). Significant differences were seen in the total number of catch per
      area (Hohenau, Ernstbrunn, Vienna Woods equal 10:9:2) and in the distribution of
      the various rodent species in the respective areas. Borrelia strains were grown
      from only 65 (7%) animals, and more frequently isolated from bladder wall than
      from heart muscle, and only once from brain. Heart specimens of 223 animals were
      positive by borrelia PCR (24%), most frequently of the rodent species A.
      flavicollis (43%) and C. glareolus (38%). Borrelia afzelii was most frequently
      identified, followed by B. burgdorferi sensu stricto, B. garinii and by mixed
      infection of B. afzelii with B. burgdorferi sensu stricto. B. garinii was most
      frequently detected in heart samples of A. sylvaticus (about 20%). In about 3% of
      PCR positive samples the identification of one of the three mentioned genospecies
      of borrelia could not be ascertained with the test panel used. The results
      confirm the rodent species A. flavicollis, A. sylvaticus, M. arvalis and C.
      glareolus as reservoir animals for B. afzelii, B. garinii and B. burgdorferi
      sensu stricto, agents of Lyme borreliosis. Notable is the salient presence of B.
      garinii in heart specimens of A. sylvaticus.

PMID- 17186172
TI  - Ticks (Ixodidae) from passerine birds in the Carpathian region.
AB  - Birds have been found to be a reservoir host of borrelia. In order to assess the
      situation in Slovakia ticks were collected from a total of 3057 mist-netted,
      ringed and released passerine birds in two locations at 500 m (in 2001) and 1000
      m (in 2003) above sea level in the Bukovske Vrchy Hills, part of the Carpathian
      region in the north-east of Slovakia. A total of 75 birds of 16 species were
      infested with subadult ticks of Ixodes ricinus species (prevalence of
      parasitization 5%). Sixty-two larvae from 31 birds of 9 species and 80 nymphs
      from 52 birds of 15 species were found. The highest intensity of parasitization
      was observed on blackbirds Turdus merula, song thrushes T. philomelos and
      dunnocks Prunella modularis. Six Ixodes ricinus adult ticks were found on humans
      working with birds, and one I. ricinus female tick on their dog. In ticks, the
      presence of Rickettsia sp., Coxiella burnetii, Borrelia burgdorferi sensu lato
      and members of the Anaplasmataceae and Piroplasmidae, were investigated by
      polymerase chain reaction, followed by sequence analysis. Rickettsia sp. was
      found in 1 nymph from the European robin Erithacus rubecula, in 3 adult ticks (1
      male, 2 females) from humans and in the tick from the dog. The closely related
      Ehrlichia- like species "Schotti variant" was detected in 1 nymph from the song
      thrush. Borrelia afzelii was identified in 1 male and B. garinii in 1 female tick
      collected on humans. Ixodes ricinus was found to be the vector of a wide spectrum
      of tick-borne pathogens in a mountainous area of the Carpathians. Because of the
      low yield of ticks and pathogens the importance of birds as reservoir hosts is
      still poorly understood.

PMID- 17186173
TI  - Severe tick-borne encephalitis in Slovenia in the years 2001-2005: time for a
      mass vaccination campaign?
AB  - The aim of this retrospective study was to assess some clinical, epidemiological
      and laboratory parameters of severe tick-borne encephalitis in Slovenia in the
      last five years, to compare them with published data, and to estimate need for
      providing a policy of active immunization. Thirty-three adult patients with a
      severe course of the disease, admitted to the intensive care unit of the
      Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia
      during a five year period, participated. All the patients had specific serum IgM
      antibodies against tick-borne encephalitis virus at admissions and IgG antibodies
      were present in 29 out of 33 patients. Twenty-two patients were admitted because
      of severe consciousness disturbances, nine suffered from spinal nerve paralysis,
      in two patients cranial nerve paralysis was observed, and one suffered from
      generalized tonic-clonic seizures. Ten patients were mechanically ventilated and
      three died. Leukocytosis in peripheral veins was found in twenty-one patients and
      nine had a C-reactive protein serum concentration over 50 mg/l. Nineteen patients
      had a cerebrospinal fluid leukocyte count exceeding 100 x 10(6)/l and a
      cerebrospinal fluid protein concentration was over the cut-off value of 0.45 g/l
      in majority. The findings of the present study confirmed some previous reports
      about clinical, epidemiological and laboratory characteristics of patients with
      severe tick-borne encephalitis. We have found that tick-borne encephalitis in
      Slovenia has a relatively low fatality rate. However, the severe course with long
      lasting sequelae of the disease justifies vaccination of a risk population in
      endemic areas.

PMID- 17186174
TI  - Clinical-pathological conference series from the Medical University of Graz :
      case no. 131: elevated transaminases in a 30-year-old male.

PMID- 17186175
TI  - [What illness really caused Mozart's death? Mozart in the reflection of
      medicine].

PMID- 17186180
TI  - The macrophage lineage as a mediator of remodelling disease: focussed topic
      meeting organized by the Inflammation Research Association, Hilton Hotel, East
      Brunswick, NJ, USA, 17th March 2006.

PMID- 17186181
TI  - Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease
      (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and
      vascular response.
AB  - Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, safe in clinical
      trials for inflammatory bowel disease (PL 10, PLD 116, PLD 14736, Pliva,
      Croatia)) has a particular cytoprotective/adaptive cytoprotective activity. The
      cytoprotective/adaptive cytoprotection researches largely neglect that stomach
      distension could per se jeopardize the mucosal integrity, with constantly
      stretched mucosa and blood vessels, and sphincters more prone for reflux
      induction. After absolute alcohol instillation in fully distended rat stomach,
      gastric, esophageal and duodenal lesions occur. Throughout next 3 min, left
      gastric artery blood vessels clearly disappear at the serosal site, indicative
      for loss of vessels both integrity and function. Contrary, constant vessels
      presentation could predict the beneficial effect of applied agent. After
      pentadecapeptide BPC 157 instillation into the stomach the vessels presentation
      remains constant, and lesions of stomach, esophagus, and duodenum are inhibited.
      Standards (atropine, ranitidine, omeprazole) could only slightly improve the
      vessels presentation compared to control values, and they have only a partial
      effect on the lesions. In this review we emphasize BPC 157 unusual stability, and
      some of its important effects: effectiveness against various lesions in
      gastrointestinal tract, on nitric oxide (NO)-system, and NO-agents effects, on
      somatosensory neurons, salivary glands function, recovery of AMP-ADP-ATP system,
      endothelium protection, effect on endothelin, and on angiogenesis promotion. It
      also antagonizes other alcohol effects, including acute and chronic intoxication.
      Given peripherally, it counteracts the consequence of central dopamine system
      disturbances (receptor blockade), and induces serotonin release in substantia
      nigra. Therapeutic potential of BPC 157 as a cytoprotective agent is also seen in
      its capability to heal various wounds. Given directly into the stomach, BPC 157
      instantly recovers disturbed lower esophageal and pyloric sphincter pressure in
      rats after 12-20 months of untreated esophagitis. All these could be suggestive
      for its role as a natural protectant in gastric juice with particular function
      throughout stomach distension.

PMID- 17186182
TI  - Lafutidine can improve the quality of gastric ulcer healing in humans: a
      randomized, controlled, multicenter trial.
AB  - Improving the quality of ulcer healing (QOUH) is one of the valid methods of
      prevention of relapse of gastric ulcers. We investigated the effect of lafutidine
      on the QOUH of gastric ulcer compared with famotidine in a randomized, multi
      centre controlled trial. Consecutive 80 patients with a gastric ulcer were
      randomly assigned to receive twice daily either lafutidine (10 mg) or famotidine
      (20 mg) for 12 weeks. Esophagogastroduodenoscopy was performed to examine the
      ulcer healing rate and rate of flat type ulcer scars using dye-contrast. The
      gastric ulcer healing rate was 92.1% in the lafutidine group (35/38) and 94.7% in
      the famotidine group (36/38). The rate of flat-type ulcer scars was significantly
      higher in the lafutidine group (68.4%, 26/38) than in the famotidine group
      (42.1%, 16/38) (P = 0.021). In conclusion, the present study demonstrated that
      lafutidine, as compared to famotidine, yields a significantly superior QOUH in
      patients with gastric ulcers in the clinical setting.

PMID- 17186184
TI  - Gastric microcirculation as target of gastroprotective action of glucocorticoid
      hormones in rats with desensitization of capsaicin-sensitive sensory neurons.
AB  - The study was designed to investigate whether gastric microcirculation is
      involved in mechanisms of gastroprotective action of glucocorticoids during
      desensitization of capsaicin-sensitive sensory neurons (CSN). The effects of
      desensitization of CSN on gastric microcirculation and gastric erosions after
      indomethacin administration (35 mg/kg) were compared in sham-operated rats and
      adrenalectomized animals without and with corticosterone replacement (4 mg/ kg
      s.c.). Desensitization of CSN (by capsaicin, 100 mg/kg s.c.) and adrenalectomy or
      sham-operation was performed 2 or 1 weeks before experiment, respectively. An in
      vivo microscopy technique for the direct visualization of gastric
      microcirculation and the analysis of red blood cell (RBC) velocity was employed.
      The results obtained indicate that desensitization of capsaicin-sensitive sensory
      neurons potentiate indomethacin-induced microvascular disturbances in gastric
      submucosa and mucosa and gastric injury. These potentiated effects of the
      desensitization are profoundly promoted by concomitant glucocorticoid deficiency.
      The results suggest that protective action of glucocorticoids against
      indomethacin-induced injury during desensitization of CSN is provided by their
      maintenance of gastric blood flow.

PMID- 17186183
TI  - Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in
      genetically scorbutic ODS rats.
AB  - We examined whether ascorbic acid (AA) deficiency aggravates water immersion
      restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic
      ODS rats. ODS rats received scorbutic diet with either distilled water containing
      AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric
      mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe
      gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of
      WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA
      content, while AA-sufficient rats had a large decrease in that content. AA
      deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E
      contents and increased gastric mucosal lipid peroxide content than AA-sufficient
      rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates
      WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in
      the gastric mucosa.

PMID- 17186185
TI  - [Cenesthesia as a rare differential diagnosis of persistent idiopathic facial
      pain].
AB  - Cenesthesia is portrayed as a rare differential diagnosis to persistent
      idiopathic facial pain, including the resulting therapy with antipsychotics. In
      this case report a female patient developed persistent facial pain 2 years after
      manifestation of a depressive disorder. The symptoms appeared as a bizarre pain
      phenomenon closely resembling the psychotic phenomenon of cenesthesia (body
      hallucinations). Treatment with imipramine and doxepin or a combination of
      venlafaxin, carbamazepine, and tilidine N had not been successful. Based on
      diagnostic classification of the complaint as cenesthesia in the context of a
      depressive disorder, add-on therapy of the atypical antipsychotic ziprasidone was
      administered. This led to clear improvements in mood and pain symptoms after 4
      weeks of treatment.

PMID- 17186186
TI  - [Carbamazepine intoxication. Complication of alcohol detoxification with combined
      carbamazepine and tiapride].
AB  - The advantages of alcohol detoxification treatment with combined carbamazepine
      and tiapride compared to benzodiazepines or clomethiazole is a lower level of
      sedation and lack of addictive potential. We report a case of carbamazepine
      intoxication with serum levels up to 19 mg/l in an otherwise healthy 45-year-old
      alcohol-dependent male after treatment with 600 mg carbamazepine and 600 mg
      tiapride per day. Medication was discontinued immediately and a purgative was
      administered. We were able to combat the intoxication but the assumed good
      tolerance of the combined treatment with carbamazepine and tiapride for alcohol
      detoxification still has to be proven.

PMID- 17186187
TI  - [A pilot project with clowns in psychiatric clinics].
AB  - BACKGROUND: This project examines whether visits of specially trained clinic
      clowns, as established in pediatrics, would also be useful in psychiatry.
      METHODS: We describe the effects of a 6-week phase with one clown visit per week
      in a ward for acutely ill geriatric patients. The patients and medical team were
      also questioned about their attitudes towards the clowns. RESULTS: We found more
      positive attitudes in patients after this phase. CONCLUSIONS: We interpret this
      result as an indication of positive effects and sufficient reason to initiate
      similar projects in the future.

PMID- 17186188
TI  - [Symptoms involving the gastrointestinal tract].
AB  - Symptoms involving the gastrointestinal tract are very common in patients who
      require palliative treatment. They can be caused by the patient's underlying
      (malignant) disease or by the treatment of this disease. Nausea and vomiting as
      well as constipation are of the utmost importance in this context due both to
      their frequency as well as their complex consequences. A careful evaluation of
      the patient's history combined with a few diagnostic procedures will help to
      provide a treatment which is orientated on pathophysiology.

PMID- 17186189
TI  - [Paraneoplastic syndrome in renal cell carcinoma].
AB  - Renal cell carcinoma associated paraneoplastic symptoms include constitutional
      symptoms as well as specific metabolic and biochemical abnormalities. These are
      present in up to 40% of patients with renal cell carcinoma during the course of
      the disease. This report provides information on the most common manifestations
      and their therapy; some rare variants are also mentioned. The importance of
      paraneoplasia lies partly in the fact that paraneoplastic symptoms may be the
      precursor of either primary or recurrent disease. The presence of paraneoplastic
      manifestations does not necessarily imply a poor prognosis or metastatic disease.

PMID- 17186190
TI  - [Palliative and supportive therapy in cases of renal cell carcinoma].
AB  - At the time of diagnosis, 25-30% of all patients with renal cell carcinoma
      already present with metastatic disease. Furthermore, 20-30% of patients with
      renal cell carcinoma will have progressive disease despite radical nephrectomy
      with complete tumor resection. In this review, we discuss the current therapeutic
      options for patients with metastatic renal cell carcinoma: These include
      palliative radical nephrectomy, surgery of metastasis, tumor embolisation and
      medical treatment options (e.g. immunotherapy, chemotherapy and targeted
      therapy), as well as supportive pain treatment.

PMID- 17186191
TI  - [Brain metastases in cases of renal cell carcinoma].
AB  - Brain metastases represent the most common intracranial neoplasia. The lung,
      breast and kidney are the primary tumor locations most often associated with
      brain metastasis. Seizures and neurological impairment are typical manifestations
      of neoplastic cerebral dissemination, which, when untreated, usually lead to
      death within a few months. In this review, we discuss whole brain radiotherapy,
      surgical resection and stereotactic radiosurgery as the currently used
      therapeutic options for renal cell cancer metastasis in the brain.

PMID- 17186192
TI  - [Urethral duplication in a male child. Accessory urethra with a normotopic
      opening in a penopubic epispadias with dorsal penis deviation].
AB  - Urethral duplication is a rare deformity which can present in various forms,
      commonly together with other congenital malformations. The embryological genesis
      is unknown. The isolated deformity is most often found in young males, while for
      young females it is very rare. We report the case of a 1.5 year old male child
      having a duplicate urethra with penopubic epispadias and dorsal penis deviation.
      The child, with known penopubic epispadias grade II and dorsal penis deviation,
      presented for pediatric urological consultation involving additional diagnostics
      and therapy. Examination revealed a penopubic epispadias with an external
      urethral exit at the base of the penis. A preoperative micturating cystogram led
      to the diagnosis of an accessory central as well as an epispadic urethra. We then
      carried out urethral reconstruction with the surgical combination of both
      urethras into a single functioning unit. The penis deviation was corrected after
      Ransley in the same operation. The postoperative course and aftercare showed
      normal micturition with a normotopic urethral entry as well as a good urine
      stream without evidence of a stricture or residual urine. An duplicate urethra is
      an uncommon malformation which is, however, found more often in male patients.
      Surgery is based on the individual and must be planned dependent on the
      morphology present. In all cases, both functional and cosmetic aspects must be
      taken into account.

PMID- 17186193
TI  - [Intravesical cidofovir--instillation therapy for polyomavirus-associated
      hemorrhagic cystitis after bone marrow transplantation].
AB  - Viral infections of the urogenital tract are a potential problem in patients
      taking immunosuppressive medication. We report a 14 year old male patient with
      hemorrhagic cystitis who had undergone bone marrow transplantation for the
      treatment of acute lymphoblastic leukemia. Attempts at coagulation as well as
      instillation treatment and continuous bladder irrigation were not sufficient to
      stop bleeding. Sequential to these procedures, local instillation with cidofovir
      into the bladder was started to treat a suspected infection with polyomavirus and
      the gross hematuria stopped within a few days.

PMID- 17186194
TI  - [Wolfgang Amadeus Mozart: not a urologic but an infectious pathologic
      biography?].

PMID- 17186196
TI  - [Malignant lymphomas as organ diseases].

PMID- 17186195
TI  - [Endometriosis of the ureter and urinary bladder].
AB  - Endometriosis is a benign growth of ectopic endometrial mucous membrane which has
      maintained the histological characteristics and biological reactions of uterine
      mucous membrane. In only 1-2% of cases does it occur in the urinary system, most
      commonly in the urinary bladder. Such an endometriosis is often diagnosed very
      late due both to its commonly asymptomatic course and its rarity. Individual
      therapy is dependent on the age of the patient, the wish for children and the
      extent of the growth. For endometriosis covering a large area, surgery is
      recommended. Methods of choice are laparoscopic bladder resection for the urinary
      bladder, ureterocystoneostomy using the Psoas hitch for the distal ureter, end to
      end anastomosis or endoscopic incision for short, proximal cases, and for
      extended areas, ileum cross-bridge attachment or kidney mobilization using
      nephropexy.

PMID- 17186197
TI  - Pathway analysis identifies perturbation of genetic networks induced by butyrate
      in a bovine kidney epithelial cell line.
AB  - Ruminant species have evolved to metabolize the short-chain volatile fatty acids
      (VFA), acetate, propionate, and butyrate, to fulfill up to 70% of their nutrient
      energy requirements. The inherent VFA dependence of ruminant cells was exploited
      to add a level of increased sensitivity to the study of the role of butyrate gene
      response elements in regulatory biochemical pathways. Global gene expression
      profiles of the bovine kidney epithelial cells regulated by sodium butyrate were
      investigated with high-density oligonucleotide microarrays. The detailed
      mechanisms by which butyrate induces cell growth arrest and apoptosis were
      analyzed using the Ingenuity Pathways Knowledge Base. The functional category and
      pathway analyses of the microarray data revealed that four canonical pathways
      (Cell cycles: G2/M DNA damage checkpoint, and pyrimidine metabolism; G1/S
      checkpoint regulation and purine metabolism) were significantly perturbed. The
      biologically relevant networks and pathways of these genes were also identified.
      IGF2, TGFB1, TP53, E2F4, and CDC2 were established as being centered in these
      genomic networks. The present findings provide a basis for understanding the full
      range of the biological roles and the molecular mechanisms that butyrate may play
      in animal cell growth, proliferation, and energy metabolisms.

PMID- 17186198
TI  - A multilevel analysis on the determinants of regional health care expenditure: a
      note.
AB  - Health care in most countries is a rather "local good" for which the fiscal
      decentralization theory applies and heterogeneity is the result. In order to
      address the issue of multijurisdictional health care in estimating income
      elasticity, we constructed a unique sample using data for 110 regions in eight
      Organisation for Economic Co-operation and Development (OECD) countries in 1997.
      We estimated this sample data with a multilevel hierarchical model. In doing
      this, we tried to identify two sources of random variation: within- and between
      country variation. The basic purpose was to find out whether the different
      relationships between health care spending and the explanatory variables are
      country specific. We concluded that to take into account the degree of fiscal
      decentralization within countries in estimating income elasticity of health
      expenditure proves to be important. Two plausible reasons lie behind this: (a)
      where there is decentralization to the regions, policies aimed at emulating
      diversity tend to increase national health care expenditure and (b) without
      fiscal decentralization, central monitoring of finance tends to reduce regional
      diversity and therefore decrease national health expenditure. The results of our
      estimation do seem to validate both these points.

PMID- 17186199
TI  - Long-term cost-effectiveness of clopidogrel in patients with acute coronary
      syndrome without ST-segment elevation in Germany.
AB  - Patients with acute coronary syndrome without ST-segment elevation receiving
      clopidogrel in addition to acetylsalicylic acid (ASA) showed a 20% risk reduction
      in comparison to patients receiving ASA monotherapy (CURE trial). Economic models
      for assessing the impact on costs exist for several countries but not for Germany
      on a long-term basis. The objective of this model adaptation is to assess the
      long-term economic impact of clopidogrel taken in addition to ASA in Germany. A
      Markov model with six states [at risk, first year with stroke, following years
      with stroke, first year with new myocardial infarction (MI), following years with
      MI, and death] was adapted for Germany. Model outcome was life-years saved.
      Effects of 1-year treatment were calculated based on the CURE trial. Resource use
      for the different health states was based on published data, which included costs
      for drugs, outpatient care, hospitalization, rehabilitation and nursing. Risk
      data for MI and stroke were based on Swedish data and validated for the German
      adaptation. The model calculates lifetime costs and survival length. Costs were
      estimated from the payers' perspective. A series of one-way sensitivity analyses
      was conducted (follow-up costs, discount rates). The Markov analysis predicts a
      survival of 8.89years in the placebo treatment group and 9.02 years in the
      clopidogrel treatment group. The cumulated costs were euro 8,548 and euro 8,953,
      respectively. The incremental cost-effectiveness ratio (ICER) was euro 3,113 for
      each life-year saved. The model was robust regarding variations in key parameters
      in the sensitivity analysis, resulting in a range of ICER from euro 1,338 to euro
      9,322. Our results are in line with the results for other healthcare systems.
      Adding clopidogrel to ASA for patients with acute coronary syndrome without ST
      segment elevation generated an additional life-year saved at a comparably low
      value of euro 3,113. One-year treatment with clopidogrel is a cost-effective
      treatment option in patients with acute coronary syndrome from the perspective of
      a third-party payer in Germany.

PMID- 17186200
TI  - Assessment of the pharmaceutical market in Poland after accession to the European
      Union.
AB  - The Republic of Poland joined the European Union (EU) on 1 May 2004. The EU
      accession brought new opportunities to the Polish health care system and the
      pharmaceutical market. However, there are still barriers to overcome such as
      bureaucracy, lack of transparency in pricing and reimbursement, decision-making
      processes, the short period of data exclusivity, respect for intellectual
      property rights, favorisation of local companies and low health care investment.
      Additionally, drug costs outpace overall economic development, a trend which is
      universally valid for almost all EU countries and which forms one of the most
      serious factors in health care expenditure. A systematic cost-effective
      assessment, the so-called fourth hurdle (after quality, efficacy and safety), of
      prescription drugs seems a necessity in most EU countries. The Polish Ministry of
      Health has defined aims for the future health care system in the National Drug
      Policy 2004-2008, including health economical criteria and instruments. However,
      it is to be expected that for some time there will be more a reimbursement hurdle
      instead of a fourth hurdle in controlling drug expenditure. This review focuses
      on the Polish pharmaceutical market with special consideration of the history of
      the Polish health care system. It will highlight the present situation of the
      Polish health care system after EU accession and provide an outlook to its
      possible future.

PMID- 17186201
TI  - The differences in characteristics between health-care users and non-users:
      implication for introducing community-based health insurance in Burkina Faso.
AB  - The purposes of this study are to describe the characteristics of different
      health-care users, to explain such characteristics using a health demand model
      and to estimate the price-related probability change for different types of
      health care in order to provide policy guidance for the introduction of community
      based health insurance (CBI) in Burkina Faso. Data were collected from a
      household survey using a two stage cluster sampling approach. Household
      interviews were carried out during April and May 2003. In the interviewed 7,939
      individuals in 988 households, there were 558 people reported one or more illness
      episodes; two-thirds of these people did not seek professional care. Health care
      non-users display lower household income and expenditure, older age and lower
      perceived severity of disease. The main reason for choosing no-care and self-care
      was 'not enough money'. Multinomial logistic regression confirms these
      observations. Higher household cash-income, higher perceived severity of disease
      and acute disease significantly increased the probability of using western care.
      Older age and higher price-cash income ratio significantly increased the
      probability of no-care or self-care. If CBI were introduced the probability of
      using western care would increase by 4.33% and the probability of using self-care
      would reduce by 3.98%. The price-related probability change of using western care
      for lower income people is higher than for higher income although the quantity
      changed is relatively small. In conclusion, the introduction of CBI might
      increase the use of medical services, especially for the poor. Co-payment for the
      rich might be necessary. Premium adjusted for income or subsidies for the poor
      can be considered in order to absorb a greater number of poor households into CBI
      and further improve equity in terms of enrollment. However, the role of CBI in
      Burkina Faso is rather limited: it might only increase utilisation of western
      health care by a probability of 4%.

PMID- 17186202
TI  - Income-related health inequality in Belgium: a longitudinal perspective.
AB  - This paper provides new evidence on the degree of income-related inequality in
      self-assessed health in Belgium. First of all, we combine the time dimension,
      which has been shown to be very important in the analysis of inequality, and the
      use of the recently developed interval regression approach to transform a
      categorical health variable in a continuous one. Second, we measure how the long
      run inequality differs from the short-run inequality. Finally, we decompose this
      health-related income mobility index as well as the long-run concentration index
      (CI) itself into its contributors. Using data from the panel survey of Belgian
      households (1994-2002), we find that health is pro-rich distributed and that its
      inequality is underestimated by 9.45% when neglecting the dynamics of individuals
      over time. Income, education, job status and age are the most important
      contributors in the CI and the difference between the short-run and long-run
      inequality.

PMID- 17186203
TI  - Should we really worry about "launch delays" of new drugs in OECD countries?

PMID- 17186204
TI  - Innovation in hospitals: a survey of the literature.
AB  - The literature on innovation in hospitals is relatively extensive and varied. The
      purpose of this article is to conduct a critical survey, and in particular to
      highlight the functional and occupational bias that characterises it, whereby the
      sole object of innovation is medical care, and that innovation is essentially the
      work of doctors. In order to achieve this objective, four different
      (complementary or competing) concepts of the hospital are considered. In the
      first, the hospital is seen in terms of its production function, in the second,
      as a set of technical capacities, in the third, as an information system, and in
      the fourth, as a service provider and a hub in a wider system of healthcare. In
      the latter approach, hospitals are regarded as combinative providers of diverse
      and dynamic services, able to go beyond their own institutional boundaries by
      becoming part of larger networks of healthcare provision, which are themselves
      diverse and dynamic. This approach makes it possible to extend the model of
      hospital innovation to incorporate new forms of innovation and new actors in the
      innovation process, in accordance with the Schumpeterian tradition of openness.

PMID- 17186205
TI  - Patients' willingness to pay for electronic communication with their general
      practitioner.
AB  - Despite the common use of electronic communication in other aspects of everyday
      life, its use between patients and health care providers has been slow to
      diffuse. Possible explanations are security issues and lack of payment
      mechanisms. This study investigated how patients value secure electronic access
      to their general practitioner (GP). One hundred and ninety-nine patients were
      asked an open-ended willingness-to-pay (WTP) question as part of a randomised
      controlled trial. We compared the WTP values between two groups of respondents;
      one group had had the opportunity to communicate electronically with their GP for
      a year and the other group had not. Fifty-two percent of the total sample was
      willing to pay for electronic GP contact. The group of patients with access
      revealed a significantly lower WTP than the group without such access. Possible
      explanations are that the system had fewer benefits than expected, a presence of
      hypothetical bias or simply a preference for face-to-face encounters.

PMID- 17186206
TI  - Pharmacoeconomic studies in Italy: a critical review of the literature.
AB  - To assess the state of pharmacoeconomics in Italy we reviewed all the original
      studies published by Italian authors in national and international journals from
      January 1994 to December 2003. We selected 70 articles and broadly assessed 92
      economic evaluations (EEs) since some articles contained multiple analyses. We
      adopted common analysis criteria to allow methodological comparison of the
      studies. The variables investigated can be grouped into three categories: general
      methods, costs, and consequences. To further assess the quality of the EEs, we
      decided to rank them according to criteria of both clinical and economic good
      practice. Then, to complete our critical evaluation, we analysed whether
      sponsorship might have somehow affected the results. Our analysis seems to
      support the widespread scepticism of the Italian NHS decision-makers towards
      pharmacoeconomic studies, whose results seem to be biased by flawed methods and
      sponsors' interference with results.

PMID- 17186207
TI  - Characterization and performance of constructed nitrifying biofilms during
      nitrogen bioremediation of a wastewater effluent.
AB  - Constructed ammonium oxidizing biofilms (CAOB) and constructed nitrite oxidizing
      biofilms (CNOB) were characterized during the bioremediation of a wastewater
      effluent. The maximum ammonium removal rate and removal efficiency in CAOB was
      322 mg N-NH4+ m(-3) d(-1) and 96%, respectively, while in CNOB a maximum removal
      rate of 255 mg N-NH4+ m(-3) d(-1) and a removal efficiency of 76% was achieved.
      Both constructed biofilms on low-density polyester Dacron support achieved
      removal efficiencies higher than that of the concentrations normally present in
      reactors without constructed biofilms (P < 0.05). Nitrifying bacteria from the
      constructed biofilms cultures were typed by sequencing 16S rRNA genes that had
      been amplified by PCR from genomic DNA. Analysis of enrichment biofilms has
      therefore provided evidence of high removal of ammonium and the presence of
      Nitrosomonas eutropha, N. halophila and N. europaea in CAOB, while in CNOB
      Nitrobacter hamburgensis, N. winogradskyi and N. alkalicus were identified
      according to 16S rRNA gene sequences comparison. The biofilm reactors were
      nitrifying over the whole experimental period (15 days), showing a definite
      advantage of constructed biofilms for enhancing a high biomass concentration as
      evidenced by environmental electron microscopic analysis (ESEM). Our research
      demonstrates that low-density polyester Dacron can be effectively used for the
      construction of nitrifying biofilms obtaining high removal efficiencies of
      nitrogen in a relatively short time from municipal effluents from wastewater
      treatment plants. CAOB and CNOB are potentially promissory for the treatment of
      industrial wastewaters that otherwise requires very large and expensive reactors
      for efficient bioremediation of effluents.

PMID- 17186208
TI  - Statistical optimization of medium components for avilamycin production by
      Streptomyces viridochromogenes Tu57-1 using response surface methodology.
AB  - A fermentation medium for avilamycin production by Streptomyces viridochromogenes
      Tu57-1 has been optimized. Important components and their concentrations were
      investigated using fractional factorial design and Box-Behnken Design. The
      results showed that soybean flour, soluble starch, MgSO4.7H2O and CaCl2.2H2O are
      important for avilamycin production. A polynomial model related to medium
      components and avilamycin yield had been established. A high coefficient of
      determination (R2 = 0.92) was obtained that indicated good agreement between the
      experimental and predicted values of avilamycin yield. Student's T-test of each
      coefficient showed that all the linear and quadratic terms had significant effect
      (P > |T| < 0.05) on avilamycin yield. The significance of tested components was
      related to MgSO4.7H2O (0.37 g/L), CaCl2.2H2O (0.39 g/L), soybean flour (21.97
      g/L) and soluble starch (37.22 g/L). The yield of avilamycin reached 88.33 +/-
      0.94 mg/L (p < 0.05) that was 2.8-fold the initial yield.

PMID- 17186209
TI  - Isomaltulose production using free cells: optimisation of a culture medium
      containing agricultural wastes and conversion in repeated-batch processes.
AB  - The enzyme glucosyltransferase is an industrially important enzyme since it
      produces non-cariogenic isomaltulose (6-O-alpha-D-glucopyronosyl-1-6-D
      fructofuranose) from sucrose by intramolecular transglucosylation. The
      experimental designs and response surface methodology (RSM) were applied for the
      optimisation of the nutrient concentrations in the culture medium for the
      production of glucosyltransferase by Erwinia sp. D12 in shaken flasks at 200 rpm
      and 30 degrees C. A statistical analysis of the results showed that, in the range
      studied, the factors had a significant effect (P < 0.05) on glucosyltransferase
      production and the highest enzyme activity (10.84 U/ml) was observed in culture
      medium containing sugar cane molasses (150 g l(-1)), corn steep liquor (20 g l(
      1)), yeast extract Prodex Lac SD (15 g l(-1)) and K2HPO4 (0.5 g l(-1)) after 8 h
      at 30 degrees C. The production of cell biomass by the strain of Erwinia sp. D12
      was carried out in a 6.6-l fermenter with a mixing rate of 200 rpm and an
      aeration rate of 1 vvm. Fermentation time, cellular growth, medium pH and
      glucosyltransferase production were observed. The greatest glucosyltransferase
      activity was 22.49 U/ml, obtained after 8 h of fermentation. The isomaltulose
      production from sucrose was performed using free Erwinia sp. D12 cells in a batch
      process using an orbital shaker. The influence of the parameters sucrose
      concentration, temperature, pH, and cell concentration on the conversion of
      sucrose into isomaltulose was studied. The free cells showed a high conversion
      rate of sucrose into isomaltulose using batch fermentation, obtaining an
      isomaltulose yield of 72.11% from sucrose solution 35% at 35 degrees C.

PMID- 17186210
TI  - Identification of metabolites produced from N-phenylpiperazine by Mycobacterium
      spp.
AB  - Mycobacterium sp. 7E1B1W and seven other mycobacterial strains known to degrade
      hydrocarbons were investigated to determine their ability to metabolize the
      piperazine ring, a substructure found in many drugs. Cultures were grown at 30
      degrees C in tryptic soy broth and dosed with 3.1 mM N-phenylpiperazine
      hydrochloride; samples were removed at intervals and extracted with ethyl
      acetate. Two metabolites were purified from each of the extracts by high
      performance liquid chromatography; they were identified by mass spectrometry and
      (1)H nuclear magnetic resonance spectroscopy as N-(2-anilinoethyl)acetamide and N
      acetyl-N'-phenylpiperazine. The results show that mycobacteria have the ability
      to acetylate piperazine rings and cleave carbon-nitrogen bonds.

PMID- 17186211
TI  - [The dorsal spondylodesis of rotationally unstable thoracic fractures. Is
      additional ventral stabilization necessary?].
AB  - METHODS: A total of 60 patients with solely dorsally reconstructed type C
      fractures of the thoracic spine admitted between January 2000 and December 2003
      were retrospectively evaluated. Stability was determined by measuring kyphosis of
      the vertebral body, the operated segments and of lateral bending on the basis of
      plain films and computed tomography immediately postoperatively and after 2 and
      19 months. RESULTS: There were 48% C2, 38% C1 and 13% C3 fractures. Of the
      injuries, 28% were caused by motorbike accidents, 25% by car accidents, 23% by
      falling from a height, 13% by suicidal jumps, 3% by ski accidents and 3% for
      other reasons. A total of 92% of the patients had severe thoracic trauma as
      attendant injuries, 42% further vertebral fractures, 35% a head injury, 30% an
      extremity fracture, 15% a clavicle fracture, 8% an abdominal trauma and 7% a
      fractured pelvis. At 19+/-12 months postoperatively, the angle of the operated
      segments increased by 4.7 degrees +/-4.0 degrees and that of lateral bending of
      the operated segments by 0.7 degrees +/-1.8 degrees compared to the immediate
      postoperative values. CONCLUSION: In spite of the high instability of the injured
      spine, the collective examined had no relevant postoperative loss of correction
      and no increase in lateral bending. Therefore, a solely dorsal reconstruction is
      sufficient, reasonable and economical.

PMID- 17186212
TI  - [Staging of esophageal cancer using ultrasound].
AB  - The early diagnosis of esophageal cancer is crucial for the prognosis of the
      disease. In contrast to cancer of the upper aerodigestive tract, the mucosa of
      the esophagus is not visible without the appropriate equipment. In addition to
      endoscopy, imaging of the esophagus is crucial for early detection of the
      esophageal cancer. Ultrasound of the esophagus can be performed easily and--in
      contrast to other imaging techniques--without side effects. Different modes of
      ultrasound can be performed. First, transcutaneous ultrasound allows one to
      detect tumors of the upper esophagus and its passage into the hypopharynx.
      Second, endosonography allows one to detect pathologies of the other esophageal
      regions including the passage into the stomach. The present review discusses the
      impact of both techniques against the background of the international literature.

PMID- 17186213
TI  - Better days are coming for Riley-Day patients.

PMID- 17186214
TI  - A new method for spatially selective, non-invasive activation of neurons: concept
      and computer simulation.
AB  - Currently available non-invasive neurostimulation devices, using skin electrodes
      or externally applied magnetic coils, are not capable of producing a local
      stimulation maximum deep inside a homogeneous conductor, because of a fundamental
      limitation inherent to the Laplace equation. In this paper, a new
      neurostimulation method (the DeepFocus method) is presented, which avoids this
      limitation by using an indirect method of producing electric currents inside
      tissues: First, cylinder-shaped ferromagnetic rotating disks of non-permanent
      magnetic material are placed near the skin and magnetized by a non-rotating
      magnetic coil. Each of the disks rotates at high speed around its own axis of
      symmetry, thus producing a purely electric Lorentz force field having a non-zero
      divergence outside the disk, and therefore giving rise to charge accumulations
      inside the tissues. Subsequently, the magnetic field is switched off suddenly,
      causing a re-distribution of charge, and hence short-lived electrical currents,
      which can be used to activate neurons. Two magnet configurations are presented in
      this paper, and analyzed by computer simulation, showing that the DeepFocus
      method produces a maximum current density (the 'focus') deep inside the
      conducting body. The field strength thus created in the focus (7.9 V/m) is strong
      enough to activate thick myelinated fibers, but can be kept below the threshold
      for C-fibers, which makes the new method a possible tool for pain mitigation by
      targeted neurostimulation.

PMID- 17186215
TI  - Assessment of the importance of alpha-amylase inhibitor-2 in bruchid resistance
      of wild common bean.
AB  - Both alpha-amylase inhibitor-2 (alphaAI-2) and arcelin have been implicated in
      resistance of wild common bean (Phaseolus vulgaris L.) to the Mexican bean weevil
      (Zabrotes subfasciatus Boheman). Near isogenic lines (NILs) for arcelin 1-5 were
      generated by backcrossing wild common bean accessions with a cultivated variety.
      Whereas seeds of a wild accession (G12953) containing both alphaAI-2 and arcelin
      4 were completely resistant to Z. subfasciatus, those of the corresponding NIL
      were susceptible to infestation, suggesting that the principal determinant of
      resistance was lost during backcrossing. Three independent lines of transgenic
      azuki bean [Vigna angularis (Willd.) Ohwi and Ohashi] expressing alphaAI-2
      accumulated high levels of this protein in seeds. The expression of alphaAI-2 in
      these lines conferred protection against the azuki bean weevil (Callosobruchus
      chinensis L.), likely through inhibition of larval digestive alpha-amylase.
      However, although the seed content of alphaAI-2 in these transgenic lines was
      similar to that in a wild accession of common bean (G12953), it did not confer a
      level of resistance to Z. subfasciatus similar to that of the wild accession.
      These results suggest that alphaAI-2 alone does not provide a high level of
      resistance to Z. subfasciatus. However, alphaAI-2 is an effective insecticidal
      protein with a spectrum of activity distinct from that of alphaAI-1, and it may
      prove beneficial in genetic engineering of insect resistance in legumes.

PMID- 17186217
TI  - Carotenoid biosynthesis structural genes in carrot (Daucus carota): isolation,
      sequence-characterization, single nucleotide polymorphism (SNP) markers and
      genome mapping.
AB  - Carotenoid pigments are important components of the human diet and carrots are
      the main dietary sources of the vitamin A precursors alpha- and beta-carotene.
      Carotenoids play essential biological roles in plants and the genes coding for
      the carotenoid pathway enzymes are evolutionarily conserved, but little
      information exists about these genes for carrot. In this study, we utilized
      published carrot sequences as well as heterologous PCR approaches with primers
      derived from sequence information of other plant species to isolate 24 putative
      genes coding for carotenoid biosynthesis enzymes in carrot. Twenty-two of these
      genes were placed on the carrot genetic linkage map developed from a cross
      between orange-rooted and white-rooted carrot. The carotenoid genes were
      distributed in eight of the nine linkage groups in the carrot genome recommending
      their use for merging maps. Two genes co-localized with a genomic region spanning
      one of the most significant quantitative trait loci (QTL) for carotenoid
      accumulation. Carotenoid biosynthesis cDNAs linked to root color mutations and to
      QTL for carotenoid accumulation may suggest a functional role for them as
      candidate genes. RACE PCR and reverse transcriptase PCR were used to amplify the
      full-length transcript for twenty expressed carotenoid biosynthesis genes and
      sequences were submitted to GenBank. The cloning and sequence information of
      these genes is useful for PCR-based expression studies and may point toward
      transgenic approaches to manipulate carotenoid content in carrot.

PMID- 17186216
TI  - A genetic linkage map of Phaseolus vulgaris L. and localization of genes for
      specific resistance to six races of anthracnose (Colletotrichum lindemuthianum).
AB  - A genetic map of common bean was constructed using 197 markers including 152
      RAPDs, 32 RFLPs, 12 SCARs, and 1 morphological marker. The map was established by
      using a F(2) population of 85 individuals from the cross between a line derived
      from the Spanish landrace Andecha (Andean origin) and the Mesoamerican genotype
      A252. The resulting map covers about 1,401.9 cM, with an average marker distance
      of 7.1 cM and includes molecular markers linked to disease resistance genes for
      anthracnose, bean common mosaic virus, bean golden yellow mosaic virus, common
      bacterial blight, and rust. Resistance to races 6, 31, 38, 39, 65, and 357 of the
      pathogenic fungus Colletotrichum lindemuthianum (anthracnose) was evaluated in
      F(3) families derived from the corresponding F(2) individuals. The intermediate
      resistance to race 65 proceeding from Andecha can be explained by a single
      dominant gene located on linkage group B1, corresponding to the Co-1 gene. The
      recombination between the resistance specificities proceeding from A252 agrees
      with the assumption that total resistance to races 6, 31, 38, 39, 65, and 357, is
      organized in two clusters. One cluster, located on B4 linkage group, includes
      individual genes for specific resistance to races 6, 38, 39, and 357. The second
      cluster is located on linkage group B11 and includes individual genes for
      specific resistance to races 6, 31, 38, 39, and 65. These two clusters correspond
      to genes Co-3/Co-9 and Co-2, respectively. It is concluded that most anthracnose
      resistance Co- genes, previously described as single major genes conferring
      resistance to several races, could be organized as clusters of different genes
      conferring race-specific resistance.

PMID- 17186218
TI  - Wide- versus specific-adaptation strategy for lucerne breeding in northern Italy.
AB  - This study is aimed at comparing wide- versus specific-adaptation strategies for
      lucerne in northern Italy on the basis of actual dry matter yield gains over 12
      harvests from phenotypic selection, assessing the value of specific genetic bases
      and selecting environments for the contrasting subregion A (no drought
      stress/sandy-loam soil) and subregion C (summer drought stress/silty-clay soil).
      A second aim is to investigate the adaptive responses of five sets of 18 half-sib
      progenies. The following selected populations were evaluated along with five
      cultivars: GW-SW, GA-SA, GA-SC, GC-SC and GC-SA (where GW, GA and GC are the
      genetic bases for wide adaptation, subregions A and C; SW, SA and SC are the
      selection environments for wide adaptation, subregions A and C). The selection
      and test environments were four artificial environments created by the factorial
      combination of two drought stress levels by two soil types. Two environments
      represented the subregions A and C whereas the combination of the other two
      environments represented the intermediate subregion B. Genotype x environment
      interaction (P < or = 0.001) due to both environmental factors and implying cross
      over interaction between the contrasting subregions occurred for the populations
      and the five selections. Specific genetic bases (GA and GC) implied gains in
      their target subregions of 5.2% for subregion A and 2.9% for subregion C compared
      with the widely adapted one (GW). The gain of SA ('no stress/sandy-loam soil')
      over SC ('stress/silty-clay soil') decreased from subregion A (10.6%) through
      subregion C (1.7%) but exhibited an advantage per se across environments of 5.4%.
      The best specific selections (GA-SA for subregions A and B; GC-SA for subregion
      C) implied higher yields of 9.8% in subregion A and 6.5% in subregion C, and over
      twofold greater selection efficiency across the region, relative to GW-SW. Half
      sib progeny x artificial environment interaction (P < or = 0.05) occurred in
      three sets of progenies whose parents belonged to cultivars with different or
      similar adaptation.

PMID- 17186219
TI  - Functional analysis of human glucokinase gene mutations causing MODY2: exploring
      the regulatory mechanisms of glucokinase activity.
AB  - AIMS/HYPOTHESIS: Glucokinase (GCK) acts as a glucose sensor in the pancreatic
      beta cell and regulates insulin secretion. In the gene encoding GCK the
      heterozygous mutations that result in enzyme inactivation cause MODY2. Functional
      studies of naturally occurring GCK mutations associated with hyperglycaemia
      provide further insight into the biochemical basis of glucose sensor regulation.
      MATERIALS AND METHODS: Identification of GCK mutations in selected MODY patients
      was performed by single-strand conformation polymorphism and direct sequencing.
      The kinetic parameters and thermal stability of recombinant mutant human GCK were
      determined, and in pull-down assays the effect of these mutations on the
      association of GCK with glucokinase (hexokinase 4) regulator (GCKR, also known as
      glucokinase regulatory protein [GKRP]) and 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase (PFKFB1, also known as PFK2) was tested. RESULTS: We identified
      three novel GCK mutations: the insertion of an asparagine residue at position 161
      (inserN161) and two missense mutations (M235V and R308W). We also identified a
      fourth mutation (R397L) reported in a previous work. Functional characterisation
      of these mutations revealed that insertion of asparagine residue N161 fully
      inactivates GCK, whereas the M235V and R308W mutations only partially impair
      enzymatic activity. In contrast, GCK kinetics was almost unaffected by the R397L
      mutation. Although none of these mutations affected the interaction of GCK with
      PFKFB1, we found that the R308W mutation caused protein instability and increased
      the strength of interaction with GCKR. CONCLUSIONS/INTERPRETATION: Our results
      show that different MODY2 mutations impair GCK function through different
      mechanisms such as enzymatic activity, protein stability and increased
      interaction with GCKR, helping further elucidate the regulation of GCK activity.

PMID- 17186220
TI  - Tendoscopic management of peroneal tendon disorders.
AB  - Endoscopic procedures at the hind foot have become more and more popular over the
      last few years. However, endoscopy of the peroneal tendon sheath is still not
      commonly done. We present our experience of scoping the peroneal tendon sheath to
      help establish more precise diagnosis of the pathology of the peroneal tendons
      and its associated structures and to treat it in a less invasive way.

PMID- 17186221
TI  - The value of ultrasonography in the preoperative diagnostic evaluation of
      patients with recurrent anterior shoulder dislocation: a prospective study of 44
      patients.
AB  - The purpose of this study was to investigate the value of ultrasonography in the
      pre-operative assessment of patients with recurrent post-traumatic, anterior
      shoulder instability. Forty-four consecutive patients, 44 men and 12 women, with
      unilateral, post-traumatic, recurrent instability of the shoulder were included
      in the study. One experienced radiologist examined all patients, using a 5.0 or
      7.5 MHz linear-array transducer, with the arm in different positions, one of
      which was used to provoke apprehension of the shoulder. Special attention was
      paid to the evaluation of the joint capsule, the anterior labrum, especially in
      terms of the presence of a Bankart lesion. All patients were subsequently treated
      surgically. After a diagnostic arthroscopy either an open or arthroscopic
      stabilisation of the shoulder was performed. Ultrasonography disclosed an
      unstable anterior labrum (equivalent to a Bankart lesion) in 36 shoulders; the
      lesion was verified in all 36 shoulders during arthroscopy. In three shoulders,
      arthroscopy disclosed an injured labrum, which had healed in an anterio-medial
      position on the scapular neck. In these three shoulders, ultrasonography failed
      to show any lesion. In five shoulders no Bankart lesion was found at arthroscopy.
      All these patients had increased shoulder laxity, and ultrasonography did not
      show any Bankart lesion. Furthermore a judgement of the joint capsule was not
      possible either. A bony Bankart lesion was found in four shoulders, using both
      arthroscopy and ultrasonography. The sensitivity of the ultrasonographic
      evaluation was 92%, and the specificity 100%. The positive predictive value was
      100%, and the negative predictive value 63%. Ultrasonography showed a high
      correlation with the arthroscopic findings, with a high sensitivity and
      specificity. Therefore, we conclude that US can give important pre-operative
      information in patients with recurrent, unilateral, post-traumatic, anterior
      shoulder instability.

PMID- 17186222
TI  - Genotypic and phenotypic diversity of cyanobacteria assigned to the genus
      Phormidium (Oscillatoriales) from different habitats and geographical sites.
AB  - In this study, 30 strains of filamentous, non-heterocystous cyanobacteria from
      different habitats and different geographical regions assigned to diverse
      oscillatorian genera but here collectively referred to as members of the
      Phormidium group have been characterized using a polyphasic approach by comparing
      phenotypic and molecular characteristics. The phenotypic analysis dealt with cell
      and filament morphology, ultrastructure, phycoerythrin content, and complementary
      chromatic adaptation. The molecular phylogenetic analyses were based on sequences
      of the 16S rRNA gene and the adjacent intergenic transcribed spacer (ITS). The
      sequences were located on multiple branches of the inferred cyanobacterial 16S
      rRNA tree. For some, but not all, strains with identical 16S rDNA sequences, a
      higher level of discrimination was achieved by analyses of the less conserved ITS
      sequences. As shown for other cyanobacteria, no correlation was found between
      position of the strains in the phylogenetic tree and their geographic origin.
      Genetically similar strains originated from distant sites while other strains
      isolated from the same sampling site were in different phylogenetic clusters.
      Also the presence of phycoerythrin was not correlated with the strains' position
      in the phylogenetic trees. In contrast, there was some correlation among inferred
      phylogenetic relationship, original environmental habitat, and morphology.
      Closely related strains came from similar ecosystems and shared the same
      morphological and ultrastructural features. Nevertheless, structural properties
      are insufficient in themselves for identification at the genus or species level
      since some phylogenetically distant members also showed similar morphological
      traits. Our results reconfirm that the Phormidium group is not phylogenetically
      coherent and requires revision.

PMID- 17186224
TI  - An amperometric acetylthiocholine sensor based on immobilization of
      acetylcholinesterase on a multiwall carbon nanotube-cross-linked chitosan
      composite.
AB  - A simple method has been devised for immobilization of acetylcholinesterase
      (AChE)--covalent bonding to a multiwall carbon nanotube (MWNT)--cross-linked
      chitosan composite (CMC)-and a sensitive amperometric sensor for rapid detection
      of acetylthiocholine (ATCl) has been based on this. Fourier-transform infrared
      spectroscopy proved that the native structure of the immobilized enzyme was
      preserved on this chemically clean and homogeneous composite film, because of the
      excellent biocompatibility and non-toxicity of chitosan. Glutaraldehyde was used
      as cross-linker to covalently bond the AChE, and efficiently prevented leakage of
      the enzyme from the film. Because of the inherent conductive properties of the
      MWNT, the immobilized AChE had greater affinity for ATCl and excellent catalytic
      effect in the hydrolysis of ATCl, with a K(app)(m) value of 132 micromol L(-1),
      forming thiocholine, which was then oxidized to produce a detectable and rapid
      response. Under optimum conditions the amperometric current increased linearly
      with the increasing concentration of ATCl in the range 2.0-400 micromol L(-1),
      with a detection limit of 0.10 micromol L(-1). Fabrication reproducibility of the
      sensor was good and the stability was acceptable. The sensor is a promising new
      tool for characterization of enzyme inhibitors and for pesticide analysis.
      Abstract.

PMID- 17186223
TI  - Association of the met66 allele of brain-derived neurotrophic factor (BDNF) with
      smoking.
AB  - RATIONALE: It has been suggested that a susceptibility locus near the gene
      encoding the brain-derived neurotrophic factor (BDNF) contributes to individual
      differences in human addiction vulnerability. BDNF modulates several behaviors
      that are associated with addictive drugs, and upregulation of BDNF was found to
      be associated with several drugs of abuse such as amphetamine, cocaine, and
      nicotine. In this study, we addressed the question if a common BDNF missense
      variation (Val66Met) influences the risk for smoking behavior in otherwise
      healthy human volunteers. MATERIALS AND METHODS: In total, 320 healthy unrelated
      volunteers (155 male, 165 female, mean age: 38.4 +/- 14.1 years) consisting of
      43.3% never smokers, 20.9% former smokers, and 35.6% current smokers were
      investigated. RESULTS: The frequency of both Met/Met genotype and Met allele was
      significantly increased in current and in former smokers when compared to never
      smokers (chi (2) = 10.856, df = 2, p = 0.004 and chi (2) = 4.350, df = 1, p =
      0.045, respectively). CONCLUSIONS: Our results suggest that humans who carry the
      Met allele of the BDNF missense polymorphism might be more vulnerable to initiate
      and also maintain smoking.

PMID- 17186225
TI  - Human and environmental risk assessment of pharmaceuticals: differences,
      similarities, lessons from toxicology.
AB  - The presence of human and veterinary pharmaceuticals in the environment has
      caused increasing concern due their effects on ecological receptors. Improving
      the risk assessment of these compounds necessitates a quantitative understanding
      of their metabolism and elimination in the target organism (toxicokinetics),
      particularly via the ubiquitous cytochrome P-450 (CYP) system and their
      mechanisms of toxicity (toxicodynamics). This review focuses on a number of
      pharmaceuticals and veterinary medicines of environmental concern, and the
      differences and similarities between ecological and human risk assessment. CYP
      metabolism is discussed with particular reference to its ubiquity in species of
      ecological relevance. The important issue of pharmaceutical mixtures is discussed
      to assess how emerging technologies such as ecotoxicogenomics may assist in
      moving towards a more mechanism-based environmental risk assessment of
      pharmaceuticals.

PMID- 17186226
TI  - Fluorescence sensor for water in organic solvents prepared from covalent
      immobilization of 4-morpholinyl-1, 8-naphthalimide.
AB  - A new fluorescent dye, N-allyl-4-morpholinyl-1,8-naphthalimide (AMN), was
      synthesized as a fluorescence indicator in the fabrication of a sensor for
      determining water content in organic solvents. To prevent leakage of the
      fluorophore, AMN was photo-copolymerized with acrylamide, (2
      hydroxyethyl)methacrylate, and triethylene glycol dimethacrylate on a glass
      surface treated with a silanizing agent. The sensing mechanism is based on the
      solvatochromic feature of the covalently immobilized AMN. The fluorescence
      intensity of AMN decreased with increasing water contents when it was excited at
      400 nm. In the range of ca. 0.00-4.40% (v/v), the fluorescence intensity of AMN
      changed as a linear function of water content. The sensor exhibited satisfactory
      reproducibility, reversibility, and a response time (t (99)) of the order of 50
      s. The detection limit was solvent-dependent, when acetonitrile was used as the
      solvent, and the detection limit could be as low as 0.006% (v/v) of water.
      Additionally, the prepared sensor is pH-insensitive and possesses a relatively
      long lifetime of at least one month.

PMID- 17186227
TI  - Selective solid-phase extraction of tebuconazole in biological and environmental
      samples using molecularly imprinted polymers.
AB  - Molecularly imprinted polymers (MIPs) were prepared by precipitation
      polymerization using tebuconazole (TBZ) as a template. Frontal chromatography and
      selectivity experiments were used to determine the binding capabilities and
      binding specificities of different MIPs. The polymer that had the highest binding
      selectivity and capability was used as the solid-phase extraction (SPE) sorbent
      for the direct extraction of TBZ from different biological and environmental
      samples (cabbage, pannage, shrimp, orange juice and tap water). The extraction
      protocol was optimized and the optimum conditions were: conditioning with 5 mL
      methanol:acetic acid (9:1), 5 mL methanol and 5 mL water respectively, loading
      with 5 mL aqueous samples, washing with 1.2 mL acetonitrile (ACN):phosphate
      buffer (5:5, pH3), and eluting with 3 mL methanol. The MIPs were able to
      selectively recognize, effectively trap and preconcentrate TBZ over a
      concentration range of 0.5-15 micromol/L. The intraday and interday RSDs were
      less than 9.7% and 8.6%, respectively. The limit of quantification was 0.1
      micromol/L. Under optimum conditions, the MISPE recoveries of spiked cabbage,
      pannage, shrimp, orange juice and tap water were 62.3%, 75.8%, 71.6%, 89% and
      93.9%, respectively. MISPE gave better HPLC separation efficiencies and higher
      recoveries than C18 SPE and strong cation exchange (SCX) SPE.

PMID- 17186228
TI  - Size prediction of recombinant human growth hormone nanoparticles produced by
      supercritical fluid precipitation.
AB  - Solution-enhanced dispersion by supercritical fluids (SEDS) was applied to
      produce nano-sized recombinant human growth hormone (hGH) particles. Ethanol was
      used to help the supercritical carbon dioxide to extract water from the aqueous
      protein solution. Various sizes of hGH nanoparticles were successfully prepared
      with a narrow particle size distribution from aqueous ethanol solution without
      using any additive. The theoretical particle sizes were deduced from the
      calculated droplet sizes based on a modified Jasuja's equation. The calculated
      mean particle sizes and the experimentally obtained ones were compared and the
      results showed an excellent correlation coefficient (R (2)) of 0.995.

PMID- 17186229
TI  - Assessment of enrofloxacin and ciprofloxacin accumulation in pig and calf hair by
      HPLC and fluorimetric detection.
AB  - Enrofloxacin is a synthetic bacteriostatic administered in veterinary therapy. It
      can also be used illegally as a growth promoter to enhance feed efficiency and
      weight gain. This practice is banned in several countries due to its potential
      negative effects on the environment and human health. A suitable method for
      extracting and quantifying enrofloxacin (ENR) and its main metabolite
      ciprofloxacin (CPR) in cattle and pig hair by high-performance liquid
      chromatography-fluorimetric detection (HPLC-FLD) had been proposed. ENR and CPR
      were extracted from hair samples with methanol acidified with trifluoroacetic
      acid for 24 h at 70 degrees C. The extracts were evaporated and redissolved in
      the mobile phase before injection. This simplified procedure enabled the
      detection of both CPR and ENR at ng g-1 levels (limit of detection 4-5 ng g-1)
      without further purification. Detectable residues of ENR were found in calf and
      pig hairs after the pharmacological treatment was started. Mean concentrations of
      quinolone (ENR, CPR) in contaminated hairs ranged from 20 to 2,518 ng g-1 in
      calves and from 152 to 1,140 ng g-1 in pigs. Hair pigmentation enhanced quinolone
      accumulation significantly. Hair analysis seems to increase the time window
      available for the retrospective detection of illegal ENR administration compared
      to edible tissue analysis.

PMID- 17186230
TI  - Nonoperative management of perforated appendicitis in children: can CT predict
      outcome?
AB  - BACKGROUND: The optimal treatment of perforated appendicitis remains
      controversial, but there is a trend toward nonoperative management. CT scanning
      might be helpful in determining which patients could benefit from this treatment
      option. OBJECTIVE: To determine the value of CT imaging in predicting clinical
      success or failure in children with nonoperative management of perforated
      appendicitis. MATERIALS AND METHODS: Admission CT scans of 34 children with
      perforated appendicitis treated nonoperatively between January 2003 and June 2006
      were retrospectively reviewed. All children were given intravenous antibiotics.
      Clinical outcome was correlated with imaging findings including the maximal area,
      number and complexity of collections, presence of an appendicolith or
      extraluminal air, and extent of intra-abdominal disease outside the right lower
      quadrant. Patients with an accessible simple collection were drained if their
      clinical condition did not improve. RESULTS: Successful nonoperative management
      was achieved in 20 patients; 14 patients failed nonoperative therapy. The
      presence of collections in three or more sectors (defined as the pelvis and four
      abdominal quadrants) correlated strongly with clinical failure (P < 0.05), while
      there was no correlation found between clinical outcome and the presence of an
      appendicolith, extraluminal air, distant ascites, and collection size or
      complexity. CONCLUSION: In the nonoperative management of children with
      perforated appendicitis, admission CT findings demonstrating disease beyond the
      right lower quadrant correlate with treatment failure.

PMID- 17186231
TI  - Pseudodissection of the aorta.
AB  - Motion of the aortic wall resulting in the appearance of aortic dissection on CT
      is a well-described artifact in the adult radiology literature. Aortic dissection
      is rare in the pediatric population, and literature on pediatric CT angiography
      has not included recognition of this pitfall in the diagnosis of children. The
      current case illustrates a patient at risk of aortic dissection and a false
      positive CT diagnosis as a result of this artifact.

PMID- 17186232
TI  - "Hair-on-end" skull induced by long-term G-CSF treatment in severe congenital
      neutropenia.
AB  - "Hair-on-end" skull changes are typically seen in individuals suffering from
      thalassaemia. They are induced by widening of the diploic space due to marrow
      expansion that is a consequence of ineffective and excessive erythropoiesis. We
      present a child with severe congenital neutropenia who exhibited the typical hair
      on-end sign on plain skull radiographs and MRI. In this patient the skull changes
      were very likely induced by the expansion of white blood cell precursors induced
      by long-term daily injections of recombinant human granulocyte colony stimulating
      factor (G-CSF) to treat his confounding disease. This case report is the first
      description of hair-on-end changes associated with the use of G-CSF.

PMID- 17186233
TI  - 2005 PRETEXT: a revised staging system for primary malignant liver tumours of
      childhood developed by the SIOPEL group.
AB  - Over the last 15 years, various oncology groups throughout the world have used
      the PRETEXT system for staging malignant primary liver tumours of childhood. This
      paper, written by members of the radiology and surgery committees of the
      International Childhood Liver Tumor Strategy Group (SIOPEL), presents various
      clarifications and revisions to the original PRETEXT system.

PMID- 17186234
TI  - External electric control of the proton pumping in bacteriorhodopsin.
AB  - Comparative analysis of the photoelectric response of dried films of purple
      membranes (PM) depending on their degree of orientation is presented. Time
      dependence of the photo-induced protein electric response signal (PERS) of
      oriented and non-oriented films to a single laser pulse in the presence of the
      external electric field (EEF) was experimentally determined. The signal does not
      appear in the non-oriented films when the EEF is absent, whereas the PERS of the
      oriented PM films demonstrates the variable polarity on the microsecond time
      scale. In the presence of the EEF the PERS of the non-oriented film rises
      exponentially preserving the same polarization. The polarization of the PERS
      changes by changing the polarity of the EEF with no influence on the time
      constant of the PERS kinetics. The EEF effect on the PERS of the oriented films
      is more complicated. By subtracting the PERS when EEF not equal 0 from the PERS
      when EEF = 0 the resulting signal is comparable to that of the non-oriented
      films. Generalizing the experimental data we conclude that the EEF influence is
      of the same origin for the films of any orientation. To explain the experimental
      results the two-state model is suggested. It assumes that the EEF directionally
      changes the pK(a) values of the Schiff base (SB) and of the proton acceptor
      aspartic acid D85 in bacteriorhodopsin. Because of that the SB-->D85 proton
      transfer might be blocked and consequently the L-->M intermediate transition
      should vanish. Thus, on the characteristic time scale tau( L --> M )
      approximately 30 micros; both intermediates, the M intermediate, appearing under
      normal conditions, and the L intermediate as persisting under the blocked
      conditions when D85 is protonated, should coexist in the film. The total PERS is
      a result of the potentials corresponding to the electrogenic products of
      intermediates L and M that are of the opposite polarity. It is concluded that the
      ratio of bacteriorhodopsin concentrations corresponding to the L and M
      intermediates is driven by the EEF and, consequently, it should define the PERS
      of the non-oriented films. According to this model the orientation degree of the
      film could be evaluated by describing the PERS.

PMID- 17186235
TI  - Membrane binding of a lipidated N-Ras protein studied in lipid monolayers.
AB  - The adsorption of doubly lipidated full-length N-Ras protein on 1,2-dipalmitoyl
      sn-phosphatidylcholine (DPPC) monolayers was studied by lateral pressure
      analysis, grazing incidence X-ray diffraction (GIXD), and specular reflectivity
      (XR). N-Ras protein adsorbs to the DPPC monolayer (lateral pressure of 20 mN/m)
      from the subphase thereby increasing the lateral pressure in the monolayer by 4
      mN/m. The protein insertion does not alter the tilt angle and structure of the
      lipid molecules at the air/water interface but influences the electron density
      profile of the monolayer. Further, electron density differences into the subphase
      were observed. The Fresnel normalized reflectivity could be reconstructed in the
      analysis using box models yielding electron density profiles of the DPPC
      monolayer in the absence and in the presence of N-Ras protein. The electron
      density profiles of the DPPC monolayer in the presence of Ras showed clear
      intensity variations in the headgroup/glycerol/upper chain region, the so-called
      interface region where previous bilayer studies had confirmed Ras binding.

PMID- 17186236
TI  - Mutagenesis of a bacteriophage lytic enzyme PlyGBS significantly increases its
      antibacterial activity against group B streptococci.
AB  - Group B streptococci (GBS) are the leading cause of neonatal meningitis and
      sepsis worldwide. Intrapartum antibiotic prophylaxis (IAP) is the current
      prevention strategy given to pregnant women with confirmed vaginal GBS
      colonization. Due to antibiotic resistance identified in GBS, we previously
      developed another strategy using a bacteriophage lytic enzyme, PlyGBS, to reduce
      vaginal GBS colonization. In this study, various DNA mutagenesis methods were
      explored to produce PlyGBS mutants with increased lytic activity against GBS.
      Several hyperactive mutants were identified that contain only the endopeptidase
      domain found in the N-terminal region of PlyGBS and represent only about one
      third of the wild-type PlyGBS in length. Significantly, these mutants not only
      have 18-28-fold increases in specific activities compared to PlyGBS, but they
      also have a similar activity spectrum against several streptococcal species. One
      of the hyperactive mutants, PlyGBS90-1, reduced the GBS colonization from >5 logs
      of growth per mouse to <50 colony-forming units (cfu) 4 h post treatment (
      approximately 4-log reduction) using a single dose in a mouse vaginal model. A
      reduction in GBS colonization before delivery should significantly reduce
      neonatal GBS infection providing a safe alternative to IAP.

PMID- 17186237
TI  - Purification and characterization of laccase from Pycnoporus sanguineus and
      decolorization of an anthraquinone dye by the enzyme.
AB  - The white rot fungus Pycnoporus sanguineus produced high amount of laccase in the
      basal liquid medium without induction. Laccase was purified using
      ultrafiltration, anion-exchange chromatography, and gel filtration. The molecular
      weight of the purified laccase was estimated as 61.4 kDa by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The enzyme oxidized typical
      substrates of laccases including 2,2'-azino-bis(3-ethylbenzthiazoline-6
      sulfonate), 2,6-dimethoxyphenol, and syringaldazine. The optimum pH and
      temperature for the purified laccase were 3.0 and 65 degrees C, respectively. The
      enzyme was stable up to 40 degrees C, and high laccase activity was maintained at
      pH 2.0-5.0. Sodium azide, L-cysteine, and dithiothreitol strongly inhibited the
      laccase activity. The purified enzyme efficiently decolorized Remazol Brilliant
      Blue R in the absence of added redox mediators. The high production of P.
      sanguineus laccase as well as its decolorization ability demonstrated its
      potential applications in dye decolorization.

PMID- 17186238
TI  - Increasing synthetic performance of penicillin G acylase from Bacillus megaterium
      by site-directed mutagenesis.
AB  - Site-directed mutagenesis based on predicted modeled structure of pencillin G
      acylase from Bacillus megaterium (BmPGA) was followed to increase its performance
      in the kinetically controlled synthesis of cephalexin with high reactant
      concentrations of 133 mM 7-amino-desaceto-xycephalosporanic acid (7-ADCA) and 267
      mM D: -phenylglycine amide (D-PGA). We directed changes in amino acid residues to
      positions close to the active site that were expected to affect the catalytic
      performance of penicillin acylase: alpha Y144, alpha F145, and beta V24. Alpha
      F145 was mutated into tyrosine, alanine, and leucine. Alpha Y144 and beta V24
      were mutated into arginine and phenylalanine, respectively. The S/H ratios of
      three mutants, BmPGAalpha144R, BmPGAbeta24F, and BmPGAbeta24F+alpha144R, were up
      to 1.3-3.0 times higher values. Compared to the wild-type BmPGA,
      BmPGAbeta24F+alpha144R showed superior potential of the synthetic performance,
      allowing the accumulation of up to twofold more cephalexin at significantly
      higher conversion rates.

PMID- 17186239
TI  - Strain-typing of Lentinula edodes in China with inter simple sequence repeat
      markers.
AB  - To validate strain typing by inter simple sequence repeat (ISSR) analysis in
      Lentinula edodes cultivars, 17 Chinese L. edodes strains including 15 cultivated
      strains cultivated on a large scale and two wild strains were analyzed with the
      ISSR technique. With the use of two ISSR primers, a total of 32 DNA products were
      detected, of which, 31 DNA products (96.9% of the detected products) were
      polymorphic between two or more strains. The profiles of those two primers could
      be employed to differentiate all of the tested strains. A cluster analysis based
      on ISSR data revealed that the 17 strains could be classified into two distinct
      groups. One group consisted of eight strains in which the cultivated strains were
      H (high-temperature)-type or B (broad-temperature)-type, and the other group
      comprised cultivated strains that were of the L (low-temperature)-type or M
      (medium-temperature)-type. In contrast to the two wild strains, the genetic
      diversity of 15 cultivated strains was very rich based on a similarity
      coefficient analysis.

PMID- 17186240
TI  - R-etodolac (SDX-101) and the related indole-pyran analogues SDX-308 and SDX-309
      potentiate the antileukemic activity of standard cytotoxic agents in primary
      chronic lymphocytic leukaemia cells.
AB  - OBJECTIVE: SDX-101 is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non
      steroid anti-inflammatory drug etodolac, and has anti-tumour activity in chronic
      lymphocytic leukaemia (CLL). SDX-308 and SDX-309 are more potent, structurally
      related indole-pyran analogues of SDX-101. The current study was performed to
      investigate and quantify the cytotoxic potentiating effects resulting from a
      combination of either SDX-101, SDX-308 or SDX-309 with standard cytotoxic agents
      used in the CLL treatment today. METHODS: The lymphoma cell line U937-gtb was
      used, together with primary tumour cells isolated from seven CLL patients.
      Combinations between chlorambucil and each one of the agents etodolac, SDX-101,
      SDX-308 and SDX-309 were studied. In addition, SDX-309 was combined with
      fludarabine, doxorubicin or vincristine. Both simultaneous and sequential
      exposures were explored using the median-effect method. RESULTS: Most
      combinations were additive, which could be of clinical benefit since SDX-101 has
      been shown to be well tolerated. At the 70% effect level, synergy was observed
      between SDX-308 and chlorambucil in U937-gtb cells and in two-third of the CLL
      samples. Since chlorambucil is the most important drug in CLL therapy today and
      SDX-308 is presently targeted as the lead clinical candidate, this combination
      would be interesting for further studies. Vincristine and SDX-309 were
      synergistic in two-fourth of CLL samples. CONCLUSIONS: To conclude, the non-COX
      inhibiting etodolac-derivatives SDX-101, SDX-308 and SDX-309 are potential
      candidates for combination treatment of CLL. Especially, SDX-308 in combination
      with chlorambucil warrants further evaluation.

PMID- 17186241
TI  - Targeting c-Src kinase enhances tamoxifen's inhibitory effect on cell growth by
      modulating expression of cell cycle and survival proteins.
AB  - PURPOSE: Many studies have implicated the non-receptor tyrosine kinase c-Src in
      the development and metastatic progression of many types of cancer. In breast
      cancer, c-Src has been proposed to mediate the actions of estrogen in cell cycle
      progression. METHODS: In this study we investigated the interaction between c-Src
      inhibition and estrogen receptor (ER) function using the ER-positive and
      tamoxifen-sensitive MCF-7 breast cancer cells. RESULTS: Pharmacological
      inhibition of c-Src blocked estrogen-dependent proliferation in MCF-7 cells and
      enhanced the inhibitory effects of tamoxifen or estrogen-deprivation on cell
      growth. Maximum inhibition (95%) of cell growth was obtained when tamoxifen and c
      Src blockade were combined. Inhibition of c-Src kinase decreased levels of the ER
      targets c-Myc and cyclin D1 expression but not of Bcl-2. Nevertheless, blocking c
      Src kinase in tamoxifen-treated MCF-7 cells led to apoptosis. Inhibition of c-Src
      kinase altered the ratio of Mcl-1 isoforms in favor of cell death whereas
      expression of the proapoptotic molecules Bad, Bak, and Bax was not altered.
      Surprisingly, blocking ER function increased the levels of Bad phosphorylation at
      serine 112 (BadpS112), an inactive (nonapoptotic) form of Bad. This inactivation
      of Bad upon ER blockade seemed to depend on c-Src function as chemical inhibition
      of c-Src kinase reduced BadpS112 levels in cells with impaired ER function but
      not in estrogen-treated cells. CONCLUSION: These results indicate a crucial role
      for c-Src kinase in the survival of ER-positive breast cancer cells only when ER
      function is blocked. Therefore, this study suggests that targeting simultaneously
      c-Src and ER may effectively inhibit growth of ER-positive breast cancer.

PMID- 17186242
TI  - The mating type-specific homeodomain genes SXI1 alpha and SXI2a coordinately
      control uniparental mitochondrial inheritance in Cryptococcus neoformans.
AB  - In the great majority of sexual eukaryotes, mitochondrial genomes are inherited
      almost exclusively from a single parent. While many hypotheses have been proposed
      to explain this phenomenon, very little is known about the genetic elements
      controlling uniparental mitochondria inheritance. In the bipolar, isogamous
      basidiomycete yeast Cryptococcus neoformans, progeny from crosses between strains
      of mating type a (MATa) and mating type alpha (MATalpha) typically inherit
      mitochondrial DNA (mtDNA) from the MATa parent. We recently demonstrated that a
      mating type alpha (MATalpha)-specific gene SXI1a, controls mitochondrial
      inheritance in C. neoformans. Here, we show that another homeodomain gene SXI2a
      in the alternative mating type MATa is also required for uniparental mtDNA
      inheritance in this fungus. Disruption of SXI2a resulted in biparental mtDNA
      inheritance in the zygote population with significant numbers of progeny
      inheriting mtDNA from the MATa parent, the MATalpha parent, and both the MATa and
      the MATalpha parents. In addition, progeny from same-sex mating between MATalpha
      strains showed a biparental mitochondrial inheritance pattern. Our results
      suggest that SXI1alpha and SXI2a coordinately control uniparental mitochondrial
      inheritance in C. neoformans.

PMID- 17186243
TI  - Functional analysis of Kluyveromyces lactis carboxylic acids permeases:
      heterologous expression of KlJEN1 and KlJEN2 genes.
AB  - The present work describes a detailed physiological and molecular
      characterization of the mechanisms of transport of carboxylic acids in
      Kluyveromyces lactis. This yeast species presents two homologue genes to JEN1 of
      Saccharomyces cerevisiae: KlJEN1 encodes a monocarboxylate permease and KlJEN2
      encodes a dicarboxylic acid permease. In the strain K. lactis GG1888, expression
      of these genes does not require an inducer and activity for both transport
      systems was observed in glucose-grown cells. To confirm their key role for
      carboxylic acids transport in K. lactis, null mutants were analyzed. Heterologous
      expression in S. cerevisiae has been performed and chimeric fusions with GFP
      showed their proper localization in the plasma membrane. S. cerevisiae jen1delta
      cells transformed with KlJEN1 recovered the capacity to use lactic acid, as well
      as to transport labeled lactic acid by a mediated mechanism. When KlJEN2 was
      heterologously expressed, S. cerevisiae transformants gained the ability to
      transport labeled succinic and malic acids by a mediated mechanism, exhibiting,
      however, a poor growth in malic acid containing media. The results confirmed the
      role of KlJen1p and KlJen2p as mono and dicarboxylic acids permeases,
      respectively, not subjected to glucose repression, being fully functional in S.
      cerevisiae.

PMID- 17186244
TI  - Effect of exogenous calcium on post-thaw growth recovery and subsequent plant
      regeneration of cryopreserved embryogenic calli of Hevea brasiliensis (Mull.
      Arg.).
AB  - A reliable cryopreservation technique was developed for friable embryogenic
      callus lines of Hevea brasiliensis. The study showed that reducing the CaCl(2)
      concentration of the pre-culture medium from 9 mM to 1 or 0 mM CaCl(2) before
      cryopreservation promoted post-thaw callus growth, 1 mM being the optimum CaCl(2)
      concentration for embryo regeneration. Post-thaw callus proliferation decreased
      in line with the increase of plated callus weight. The effect of cryopreservation
      was assessed on 39 independent lines showing that cryopreservation did not affect
      embryogenic and plant regeneration for a majority of lines. The decrease in
      CaCl(2) concentration of the pre-culture medium led to a drop in callus calcium
      content indicating a direct link between the CaCl(2) concentration of the pre
      culture medium and the endogenous calcium content of the calli. It also
      highlighted the implication of tissue calcium content in cryotolerance. Callus
      water status and the different ways by which calcium could prevent cryoinjury is
      also discussed.

PMID- 17186245
TI  - Self-expanding nitinol stents for treatment of infragenicular arteries following
      unsuccessful balloon angioplasty.
AB  - The feasibility of self-expanding nitinol stents for treatment of infragenicular
      arteries following unsuccessful balloon angioplasty was assessed. Options for
      lower limb percutaneous revascularization are limited, especially for complex
      vessel obstruction. Depending on the lesion and the experience of the
      interventionalist, the failure rate of balloon angioplasty (PTA) ranges between
      10 and 40%. Until recently, no self-expanding stent for the use in the
      infragenicular arteries was available. This is the first report of the results
      for 18 consecutive patients who received 4F sheath compatible self-expanding
      nitinol stents following unsuccessful PTA or early restenosis. Twenty-four stents
      were implanted in 21 lesions for various indications residual stenosis >50% due
      to heavy calcification, flow-limiting dissection, occluding thrombus resistant to
      thrombolyis, thrombaspiration, and PTA, and early restenosis after previous PTA.
      Stent implantation was feasible in all cases. No complications occurred. After
      the stent implantation, all primarily unsuccessful interventions could be
      transformed into successful procedures with no residual stenosis >30% in any
      case. After 6 +/- 2 months, two of the 18 patients died, and 14 of the 16
      remaining patients improved clinically. At follow-up, the patency could be
      assessed in 14 stented arteries. Three stents were occluded, one stent showed
      some neointimal hyperplasia (50-70% restenosis), the remaining ten stents showed
      no restenosis (0-30%). The use of self-expanding nitinol stents in tibioperoneal
      and popliteal arteries is a safe and feasible option for the treatment of
      unsuccessful PTA. The 6-months patency is high.

PMID- 17186246
TI  - Cartilage lesions of the glenohumeral joint: diagnostic effectiveness of
      multidetector spiral CT arthrography and comparison with arthroscopy.
AB  - This study assessed the diagnostic effectiveness of multidetector spiral CT
      arthrography (MDCTa) in detecting hyaline cartilage abnormalities of the shoulder
      joint, with correlation to arthroscopy. Shoulder MDCTa images prospectively
      obtained in 22 consecutive patients (mean age, 50 years; age range, 23-74 years;
      12 female, 10 male) were evaluated for glenohumeral cartilage lesions. Two
      musculoskeletal radiologists independently analysed the cartilage surfaces of the
      humeral head and of the glenoid fossa in nine anatomical surface areas.
      Observations of MDCTa were compared to arthroscopic findings. The sensitivity and
      specificity of MDCTa for grade 2 (substance loss <50%) or higher and grade 3
      (substance loss >or=50%) or higher cartilage lesions, the Spearman correlation
      coefficient between arthrographic and arthroscopic grading, and K statistics for
      assessing Intra and Interobserver reproducibility were determined. At MDCTa,
      sensitivities and specificities ranged between 80% and 94% for the detection of
      grade 2 or higher cartilage lesions, and between 88% and 98% for the detection of
      grade 3 or higher cartilage lesions. Spearman correlation coefficients between
      MDCTa and arthroscopic grading of articular surfaces ranged between 0.532 and
      0.651. Interobserver agreement was moderate for grading all articular surfaces
      (kappa = 0.457), but substantial to almost perfect for detecting lesions with
      substance loss (kappa, 0.618-0.876). In conclusion, MDCTa is accurate for the
      study of cartilage surface in the entire shoulder joint. This technique may
      beneficially impact patient's management by means of selecting the proper
      treatment approach.

PMID- 17186247
TI  - Significance of mesorectal volume in staging of rectal cancer with magnetic
      resonance imaging and the assessment of involvement of the mesorectal fascia.
AB  - The aim was to study the influence of mesorectal volume, as estimated by magnetic
      resonance imaging (MRI), that is to be removed during total mesorectal excision
      (TME), on the accuracy of the first preoperative MRI of rectal cancer compared to
      histopathology, and its correlation to locoregional prognostic factors. A total
      of 267 rectal cancer patients from a multinational study (MERCURY or MRI
      equivalence study) had their mesorectal volume retrospectively estimated by
      researchers without knowledge of the assessments made by the radiologist or the
      pathologist. The evaluations made by the pathologist and the radiologist were
      then compared, including T- and N-staging, assessment of extent of extramural
      tumor invasion (the largest portion of the tumor beyond the muscularis propria or
      EMI) and distance to mesorectal fascia; the discrepancies in the results were
      correlated to the mesorectal volume. T- or N-staging accuracy by MRI and the
      difference between the EMI as measured by the pathologist and the radiologist
      were not dependent on individual mesorectal volume. There was no correlation
      between assessment of involvement of mesorectal fascia or local neighboring
      organs by MRI and histopathology with mesorectal volume. Mesorectal volume does
      not affect locoregional prognostic factors or the accuracy of local staging of
      rectal cancer.

PMID- 17186248
TI  - Evaluation of the anterior ethmoidal artery by 3D dual volume rotational digital
      subtraction angiography and native multidetector CT with multiplanar
      reformations. Initial findings.
AB  - Our purpose is to codify the anterior ethmoidal artery (AEA) course and its
      relationship with adjacent structures. Twenty patients with cerebrovascular
      disease underwent selective internal carotid dual volume angiography. Fusion of
      the vascular and bony images was obtained successively on a second console. MDCT
      of the cranium was performed in all patients. To identify the AEA course,
      multiplanar CT reformations were obtained. In all cases the entry-point of AEA
      and its course were identified by means of dual volume angiography. The
      information was confirmed by MDCT. In a second phase, we studied another 78
      patients affected by inflammatory disease and polyposis only by means of MDCT, in
      order to confirm the previous data obtained by comparison between angiography and
      MDCT. In this second phase, 110/156 vessels were indirectly detected by means of
      visualization of the ethmoidal entry point. In the remaining cases, AEA was
      directly shown due to integrity of the thin ethmoidal bone lamellae or bony
      canal. Dual volume angiography is essential to identify the course of the AEA
      (standard of reference for the interpretation of CT). In patients with benign
      rhinosinusal pathology, where invasivity techniques are not justified, MPR
      reconstructions were of pivotal importance in the evaluation of the course of the
      artery with particular reference to its relationship with the frontal recess.

PMID- 17186249
TI  - Finite element modeling of arachnid slit sensilla-I. The mechanical significance
      of different slit arrays.
AB  - Arachnid strain sensitive slit sensilla are elongated openings in the cuticle
      with aspect ratios (slit length l/slit width b) of up to 100. Planar Finite
      Element (FE) models are used to calculate the relative slit face displacements,
      Dc, at the centers of single slits and of arrangements of mechanically
      interacting slits under uni-axial compressive far-field loads. Our main objective
      is to quantitatively study the role of the following geometrical parameters in
      stimulus transformation: aspect ratio, slit shape, geometry of the slits'
      centerlines, load direction, lateral distance S, longitudinal shift lambda, and
      difference in slit length Deltal between neighboring slits. Slit face
      displacements are primarily sensitive to slit length and load direction but
      little affected by aspect ratios between 20 and 100. In stacks of five parallel
      slits at lateral distances typical of lyriform organs (S=0.03 l) the longitudinal
      shift lambda substantially influences slit compression. A change of lambda from 0
      to 0.85 l causes changes of up to 420% in Dc. Even minor morphological variations
      in the arrangements can substantially influence the stimulus transformation. The
      site of transduction in real slit sensilla does not always coincide with the
      position of maximum slit compression predicted by simplified models.

PMID- 17186251
TI  - Clear cell adenocarcinoma of the sigmoid colon.

PMID- 17186252
TI  - The novel Tau mutation G335S: clinical, neuropathological and molecular
      characterization.
AB  - Mutations in Tau cause the inherited neurodegenerative disease, frontotemporal
      dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known coding region
      mutations cluster in the microtubule-binding region, where they alter the ability
      of tau to promote microtubule assembly. Depending on the tau isoforms, this
      region consists of three or four imperfect repeats of 31 or 32 amino acids, each
      of which contains a characteristic and invariant PGGG motif. Here, we report the
      novel G335S mutation, which changes the PGGG motif of the third tau repeat to
      PGGS, in an individual who developed social withdrawal, emotional bluntness and
      stereotypic behavior at age 22, followed by disinhibition, hyperorality and
      ideomotor apraxia. Abundant tau-positive inclusions were present in neurons and
      glia in the frontotemporal cortex, hippocampus and brainstem. Sarkosyl-insoluble
      tau showed paired helical and straight filaments, as well as more irregular rope
      like filaments. The pattern of pathological tau bands was like that of Alzheimer
      disease. Experimentally, the G335S mutation resulted in a greatly reduced ability
      of tau to promote microtubule assembly, while having no significant effect on
      heparin-induced assembly of recombinant tau into filaments.

PMID- 17186250
TI  - Neurodevelopment of children with single suture craniosynostosis: a review.
AB  - INTRODUCTION: Rates of neurocognitive risk range from 35-50% of school-aged
      children with isolated single suture craniosynostosis (SSC). It has been
      hypothesized that early surgical intervention to release suture fusion reduces
      risk for increased intracranial pressure (ICP) and the corresponding risk to
      neurodevelopment. However, studies assessing children with SSC have been
      inconsistent in finding an association between neurocognitive development, age of
      surgery, and ICP. REVIEW: SSC produces notable distortion of the cranial vault
      and underlying brain mass. Although a linear relationship between skull
      distortion, ICP, and neurocognitive deficits has generally been assumed, recent
      studies have postulated an interactive process between the skull and developing
      brain that results in neuroanatomical changes that are not limited to areas
      directly beneath the fused suture. The specific neuropsychological deficits
      identified in children with SSC including problems with attention and planning,
      processing speed, visual spatial skills, language, reading, and spelling may be
      related to the anatomic differences that persist after correction of suture
      fusion. CONCLUSIONS: Available literature on neurocognitive development of
      children with SSC is suggestive of mild but persistent neuropsychological
      deficits, which become more significant as cognitive demands increase at school
      age. Anatomical studies of children without SSC are beginning to identify
      particular groups of brain structures that if disrupted or malformed, may be
      associated with specific cognitive deficits. Controlled research investigating
      the relationship between persistent anatomical changes and neurocognitive
      functioning of school-aged children with SSC is needed.

PMID- 17186253
TI  - Awareness of the benefits of folic acid and prevalence of the use of folic acid
      supplements to prevent neural tube defects among Thai women.
AB  - OBJECTIVE: To determine the level of knowledge about the usefulness of
      periconceptional folic acid supplementation among pregnant women. MATERIALS AND
      METHODS: An anonymous questionnaire was completed by selected subjects to assess
      folic acid awareness. The questionnaire was administered to pregnant women who
      were seeking antenatal care at King Chulalongkorn Memorial Hospital May to
      December 2005. The questions covered their knowledge and use of folic acid
      supplements, pregnancy intention, and demographic and socioeconomic
      characteristics. RESULTS: Out of 401 women surveyed, 76.1% of them reported that
      they had heard of folate. Of these, only 24.4% of the total subjects knew that
      folate was something important. Overall, 9.7% of the total women took folic acid
      during periconceptional period. The most common information sources on folate
      were the media. Logistic regression analysis showed that education of mother was
      the strongest predictor of having taken folic acid during the correct period.
      CONCLUSION: Although some pregnant women are aware of the need to take folic
      acid, the actual impact of the present recommendations is almost negligible.
      Information to specifically inform patients about the need to take folic acid to
      prevent neural tube defects by medias and healthcare personnel seem to improve
      the final intake of folic acid during the protective period.

PMID- 17186254
TI  - Treatment of twin reversed arterial perfusion sequence by septostomy and
      amniodrainage: a case report.
AB  - INTRODUCTION: An acardiac fetus is the most severe malformation seen in humans.
      It is an extremely rare complication, occurring in approximately 1% of all
      monozygotic twin gestations, with an incidence of about 1 in 35,000 births. This
      malformation happens as a result of the syndrome of reversed arterial perfusion
      of the acardiac twin from the other normal fetus (pump twin), due to the presence
      of arterio-arterial anastomoses in a monochorionic placenta. Several obstetric
      and perinatal complications have been associated to this anomaly and several
      treatments have been proposed to reduce the morbimortality of the pump twin.
      There's no report in MEDLINE about the treatment of twin gestations with acardiac
      fetus through septostomy. CASE REPORT: The present article reports a case of
      reversed arterial perfusion sequence complicated by polyhydramnios diagnosed at
      19th week of pregnancy, treated with septostomy and serial amniodrainage.
      DISCUSSION: This case presented it demonstrate favorable development of the
      gestation, with labor happening at 35 weeks gestation and pump twin presenting
      good vitality conditions. In cases with no major factors of bad prognosis,
      septostomy combined with amniodrainage could be an interesting therapeutic option
      for a safe and efficacious management of selected cases of TRAP sequence.

PMID- 17186255
TI  - Therapeutic options for adenomyosis: a review.
AB  - BACKGROUND: To review the literature on various therapeutic modalities for
      uterine adenomyosis. METHODS: Reviews, case-controlled studies and reports from
      November 1949 until August 2006 written in English or summarized in English
      abstracts retrieved from Medline and Pubmed using the key words: adenomyosis and
      adenomyosis therapy. RESULTS: Symptoms of adenomyosis may be alleviated by
      antiprostaglandins, sex hormones, danazol and GnRH analogs. Minor surgical
      procedures for therapy include endomyometrial ablation, laparoscopic myometrial
      electrocoagulation and adenomyoma excision. Patient's age and symptoms, desired
      fertility, site and extent of lesion and surgeon's skills should be considered in
      choosing the appropriate procedure. Endomyometrial ablation is effective for
      lesions deeper than the endometrial-myometrial junction whereas the efficacy of
      hysteroscopic ablation is limited to foci 2-3 mm deep. Focal and diffuse disease
      may be managed by laparoscopic electrocoagulation or myometrial excision with
      preservation of fertility but risk of recurrence exists. Uterine artery
      embolization assumingly invokes infarction and necrosis. Encouraging results
      reported in some cases warrant expanding its use for more experience.
      Hysterectomy is the ultimate solution for women with deep myometrial involvement
      or if future fertility is not desired. CONCLUSIONS: Various therapeutic options
      for adenomyosis, including few minimally invasive procedures became available in
      the last two decades but need evaluation and improvement.

PMID- 17186257
TI  - Pulsed-field gel electrophoresis in the identification of the origin of bacterial
      keratitis caused by Pseudomonas aeruginosa.
AB  - PURPOSE: To report the use of pulsed-field gel electrophoresis (PFGE) in the
      investigation of the origin of infectious keratitis. METHODS: A 19-year-old girl
      presented with infectious keratitis in the left eye. She was a soft contact lens
      wearer, and was noncompliant with the proper cleaning methods proposed by the
      manufacturer. Microbiological assessment was performed by means of culture and
      PFGE. RESULTS: The patient was treated successfully with topical cefalotin and
      gentamicin drops. Cultures were positive for Pseudomonas aeruginosa in the cornea
      and conjunctiva, and in the contact lens, its case and the cleaning solution.
      PFGE showed identical patterns of banding in each. CONCLUSION: In this case of
      bacterial keratitis, PFGE proved to be very useful in identifying how the
      contamination occurred.

PMID- 17186256
TI  - The protein encoded by the gene proliferation disrupter (prod) is associated with
      the telomeric retrotransposon array in Drosophila melanogaster.
AB  - We report in this paper that the PROD protein, encoded by the gene proliferation
      disrupter (prod), is associated with the telomeric chromatin in Drosophila
      melanogaster. It binds to a region just upstream of the promoter of the telomere
      specific retrotransposon HeT-A, which is located in the long 3'untranslated
      region of the element near its oligo(A) tail. Reduction of PROD in prod
      heterozygote flies results in elevated levels of HeT-A RNA in the ovaries,
      suggesting that PROD functions as a repressor of HeT-A transcriptional activity
      at the telomeres.

PMID- 17186259
TI  - Evidence for frequent divergence impairment in French dyslexic children: deficit
      of convergence relaxation or of divergence per se?
AB  - AIM: There is a controversy as to whether dyslexic children present visuo-motor
      disabilities such as vergence and accommodative problems assessed with orthoptic
      tests. The purpose of this study is to re-examine this issue in a large
      population of children. METHODS: Extensive orthoptic evaluation was made in 57
      dyslexic and 46 non-dyslexic ("normal") age-matched children. Convergence and
      divergence capacities were evaluated at two distances (30 cm and 400 cm).
      RESULTS: Binocular vision measured with stereo-acuity tests was normal in
      dyslexics. In contrast, the near point of convergence was significantly more
      remote in dyslexics; most importantly, divergence at both far and near distance
      was significantly more reduced in dyslexics (median value 4 pD and 10 pD,
      respectively, at far and near) than in "normals" (median value 6 pD and 12 pD, at
      far and near). CONCLUSION: The existence of the divergence deficit at far
      distance indicates the presence of deficit of divergence per se, independently
      from convergence and accommodation relaxation. This result is novel and
      corroborated by physiological studies indicating distinct control of convergence
      and divergence, both at the cortical and subcortical premotor level. We conclude
      that vergence deficits are frequently present in dyslexics, and that dyslexics
      should be re-educated; training should address distinctively convergence and
      divergence subsystems.

PMID- 17186258
TI  - Preclinical investigation of fluorometholone acetate as a potential new adjuvant
      during vitreous surgery.
AB  - OBJECTIVE: To examine the effects of intravitreal fluorometholone acetate (FMT)
      on the morphology and function of the retina and to investigate its possible use
      for vitreous surgery. METHODS: Brown Norway rat eyes (n = 6, 12 groups) were
      injected with 0.05 ml of SF6 gas for vitrectomization. Four weeks later, FMT
      solution was injected into the vitreous cavity/subretinal space of the
      vitrectomized eyes at doses of 10, 20, and 40 mg/ml (0.05 ml/eye, n = 12 for each
      group). The retinal function was evaluated by electroretinography (ERG) at 4 and
      8 weeks after FMT injection. Retinal toxicity was also assessed histologically by
      a light microscopy. Sham-operated eyes (0.05 ml of irrigating solution, n = 12)
      were used as control animals. FMT-assisted pars plana vitrectomy with internal
      limiting membrane (ILM) peeling was performed in primate eyes (n = 2). Retinal
      toxicity was assessed by ophthalmoscope, fluorescein angiography and electron
      microscopy three months after the vitreous surgery. RESULTS: There was no
      remarkable reduction in any ERG waves at either time interval at 4 and 8 weeks
      after the intravitreal/subretinal injection of FMT. No obvious histological
      change was observed in any of the rat eyes either. Using ophthalmoscope,
      fluorescein angiography and electron microscopy, the appearance of the primate
      retinas remained to be in a non-pathological condition. CONCLUSION: FMT appears
      to be a potentially useful tool in assisting vitreous surgery including safe ILM
      peeling.

PMID- 17186260
TI  - Pathological changes in human retinal ganglion cells associated with diabetic and
      hypertensive retinopathy.
AB  - BACKGROUND: To examine whether systemic diseases like diabetes and arterial
      hypertension, which frequently cause retinopathies leading to blindness effect
      the morphology of retinal ganglion cells (RGC). METHODS: Histological retina
      material with a history of being untreated, or laser-coagulated (LC) diabetic
      retinopathy (DR), or arterial hypertensive retinopathy (AHR) was used. The RGC
      were labeled by introducing crystals of the fluorescent carbocyanine dye DiI into
      the nerve fiber layer, which contains ganglion cell axons. RESULTS: The typical
      silhouettes of both major types of RGC, parasol and midget cells, were
      identified. The axons in DR and AHR retinas showed morphology changes such as
      irregular swelling and beading. Dendritic field sizes were significantly reduced
      in RGC of both the hypertonic and diabetic retinas. A significant reduction in
      branching frequency was evident in both the diabetic and hypertonic retinas, in
      both the midget and the parasol cells. In LC retinas, both parasol and midget RGC
      were observed within the LC spots, although their numbers were dramatically
      decreased compared with normal retinas. CONCLUSIONS: The data suggest that
      diabetes and arterial hypertonia have similar effects on the morphology of RGC,
      in addition to causing microvascular alterations and bleeding. Therefore,
      therapeutic measures and prognostic outcomes in diabetic and hypertensive
      retinopathy should also consider regressive changes in retinal neurons.

PMID- 17186262
TI  - Intravitreal bevacizumab (Avastin) for occult choroidal neovascularization in age
      related macular degeneration.
AB  - BACKGROUND: The purpose of the study is to report data on short-term safety of
      intravitreal bevacizumab treatment and its effect on visual function, central
      retinal thickness, and angiographical changes of occult choroidal
      neovascularization due to age-related macular degeneration. METHODS: A
      consecutive interventional case series of 30 patients with active subfoveal
      occult choroidal neovascularization secondary to age-related macular degeneration
      was followed after one intravitreal injection of 1.25 mg bevacizumab at baseline
      and subsequent injections following standardized criteria. At baseline and follow
      up visits patients had visual acuity assessment, intraocular pressure
      measurement, fluorescein angiography, and optical coherence tomography imaging.
      RESULTS: No serious ocular or systemic adverse events were identified. A
      significant increase of intraocular pressure or signs of retinal toxicity or
      endophthalmitis were not detected in any patient. Optical coherence tomography
      revealed significant decrease (p < 0.001) in central retinal thickness after 1
      week, 4 weeks, and 12 weeks, respectively. Fluorescein leakage decreased within 1
      week and improvement was maintained at week 12 in the majority of patients.
      Visual acuity improved or remained stable in 29 of 30 patients; improvement of 3
      or more lines was seen in 14 of 30 patients; one patients showed improvement of 6
      lines. No patient had severe vision loss of 6 lines or more; moderate vision loss
      of 3 lines was seen in one patient. Re-injections of bevacizumab according to
      standard criteria were performed one to two times during the follow-up period of
      12 weeks with a re-injection interval of 4 to 18 weeks (median 8 weeks).
      CONCLUSIONS: Short-term results suggest that intravitreal injection of
      bevacizumab is well tolerated and for the majority of patients with occult
      choroidal neovascularization in AMD results in improvement of visual acuity,
      decrease in central retina thickness, and reduction of angiographic leakage of
      the lesion. Bevacizumab as intravitreal treatment may provide a novel therapeutic
      option for selected patients with exudative AMD. Randomized prospective
      multicenter trials seem justified to further evaluate long term effects and
      impact of intravitreal bevacizumab on different subtypes of AMD compared to
      established therapies.

PMID- 17186261
TI  - Surgical removal of idiopathic epiretinal membrane with or without the assistance
      of indocyanine green: a randomised controlled clinical trial.
AB  - PURPOSE: To carry out a prospective investigation of the functional and
      morphological outcome of idiopathic epiretinal membrane (IEM) surgery with or
      without the assistance of indocyanine green (ICG) in a randomised controlled
      clinical trial. METHODS: Sixty patients who underwent vitrectomy with removal of
      IEM combined with cataract surgery were randomly allocated to two groups: 27
      patients were operated on with ICG 0.1% in glucose 5%, 33 patients without ICG.
      Functional outcome was assessed 3-4 months postoperatively with improvement of
      best-corrected visual acuity (BCVA), Amsler grid test, and automated and kinetic
      perimetry. Postoperative residual or recurrent IEM was assessed with bio
      microscopy, and macular oedema with optical coherence tomography (OCT).
      Improvement in BCVA was the main outcome measure. RESULTS: BCVA improved in 49
      patients, remained unchanged in five and decreased in five. Improvement in BCVA
      and reduction of macular oedema were statistically significant within both groups
      (P < 0.01). Improvement in BCVA was not statistically significantly different
      whether ICG was used or not [0.17 (logarithm of minimum angle of resolution;
      logMAR) with ICG and 0.24 (logMAR) without ICG] (P = 0.59). There was no
      statistically significant difference in preoperative or postoperative BCVA,
      reduction of macular oedema, postoperative Amsler grid test, or incidence of
      residual or recurrent IEM between the two groups. Visual field defects were
      detected in two patients operated on with ICG. CONCLUSIONS: Removal of IEM with
      or without the assistance of ICG equally improved visual function and macular
      morphology.

PMID- 17186263
TI  - Neurofibromatosis 2 leads to choroidal hyperfluorescence in fluorescein
      angiography.
AB  - BACKGROUND: For the diagnosis of NF 2, ocular findings like juvenile cataract,
      retinal and combined hamartomas of the retinal pigment epithelium and the retina
      as well as tumours of the optic nerve play an important role. An early diagnosis
      is essential in order to inhibit deafness from bilateral vestibular schwannoma.
      But sometimes the Manchester diagnostic criteria for NF2 are not completely
      fulfilled. Frequently, suspicious macular anatomy is found in neurofibromatosis 2
      (NF2) patients. We hypothesise that the underlying retinal pigment epithelium or
      the retina of the macular region alters in NF2 patients. Therefore, we have
      tested by fluorescence angiography whether NF2 is associated with chorioretinal
      changes. METHODS AND PATIENTS: In a prospective study, 48 patients matching the
      criteria for NF2 with known genotype underwent a complete ophthalmic examination
      including funduscopy and fluorescence angiography. The influence of the genotype
      was statistically analysed by odds ratios and their 95% confidence intervals.
      RESULTS: Eleven eyes of nine patients showed choroidal hyperfluorescence in the
      macular region on fluorescence angiography. There was staining spreading from
      grainy hyperfluorescence to minor variants of a combined hamartoma of the retina
      and the retinal pigment epithelium. All of these manifestations presented without
      leakage in the late angiographic phases. These choroidal findings were present in
      one patient with frameshift mutation, in two patients with nonsense mutations and
      in six patients with splice site mutations of the NF2 gene. The statistical
      analysis showed a significant lower risk of choroidal alterations in patients
      with somatic mosaicism, deletions and unfound mutations. CONCLUSION: Using
      fluorescence angiography pathological changes of the macular region can be
      detected in NF2 patients. The ophthalmic examination, which often is limited to
      the anterior eye segment, may play a role in finding the diagnosis in incomplete
      NIH criteria. The presented study shows chorioretinal hyperfluorecences without
      leakage of the macular region, which might be considered as a forme fruste of a
      hamartoma. Choroidal hyperfluorescences add to the spectrum of genotype-phenotype
      correlations in NF2.

PMID- 17186264
TI  - Prospective study to determine the penetration of iodide into the anterior
      chamber following preoperative application of topical 1.25% povidone-iodine.
AB  - BACKGROUND: Povidone-iodine is currently the agent of choice for pre-operative
      antisepsis in ophthalmology. Due to experimental and analytical constraints,
      iodine absorption into the anterior chamber (AC) has not yet been studied.
      However, knowledge of the details of iodine transfer into the aqueous humor (AH)
      is critical for risk assessment of local and/or systemic side effects METHODS:
      Following a 2-min antisepsis with 1.25% povidone-iodine, the AC of eligible
      cataract patients was penetrated with a 26-gauge cannula prior to any other
      intraocular manipulation. To distinguish between the iodine absorbed into the AC
      and that remaining in the hypodermic delivery syringe, we studied three different
      groups of specimens: (i) AH from the AC (n=19); (ii) Ringer's solution aspirated
      through the cannula after penetration into and immediate withdrawal from the AC
      without subsequent decontamination (n=8); and (iii) Ringer's solution aspirated
      through the cannula after penetration into and immediate withdrawal from the AC,
      and subsequent decontamination of its outer surface (n=5). Patients with pre
      operative epithelial defects were excluded from the study. To measure iodine
      absorption, iodide levels in samples were determined chromatographically (ion
      pair chromatography) and electrochemically (gold electrode). RESULTS: There was
      no difference (P=0.815) between detectable amounts of iodide in groups I and II
      (median: 24.0 microg/dl and 28.9 microg/dl, respectively). Only group III
      (median: 5.2 microg/dl) showed a statistically significant lower level of iodide
      than did groups I or II (P=0.019 and P=0.011, respectively). CONCLUSIONS: A
      healthy ocular surface behaves as a barrier to the penetration of iodine into the
      AC. Any detectable iodide in the AH after antisepsis should therefore be
      considered harmless.

PMID- 17186267
TI  - FGFR1 and anosmin-1 underlying genetically distinct forms of Kallmann syndrome
      are co-expressed and interact in olfactory bulbs.
AB  - Kallmann syndrome is a genetically heterogeneous developmental disease
      characterised by a partial or complete lack of olfactory bulb development. Two
      genes underlying this disease have so far been identified: the KAL-1 gene, which
      encodes anosmin-1, an extracellular matrix protein that promotes axonal guidance
      and branch formation in vitro; and KAL-2, which encodes the known FGFR1. The
      implication of FGFR1 and anosmin-1 in the same developmental disease led us to
      test whether anosmin-1 and FGFR1 interact during the development of the olfactory
      system. In this paper, we showed that the two proteins co-localise in the
      olfactory bulb during development in rat. Using cross-immunoprecipitation assays
      of olfactory bulb extracts, we also demonstrated that anosmin-1 and FGFR1 are
      comprised within the same protein complex. Moreover, we show that anosmin-1
      expression in CHO transfected cells increases FGFR1 accumulation, suggesting that
      anosmin-1 may act as a positive extracellular regulator of FGFR1 signalling.
      Taken together, our findings strongly suggest that anosmin-1 is an essential
      component of a FGFR1 pathway that plays a key role during olfactory bulb
      morphogenesis.

PMID- 17186266
TI  - Agrin is highly expressed by chondrocytes and is required for normal growth.
AB  - Agrin is a heparan sulfate proteoglycan that is best known for its crucial
      involvement in the organization and maintenance of postsynaptic structures at the
      neuromuscular junction. Consistent with this role, mice deficient of agrin die at
      birth due to respiratory failure. Here we examined the early postnatal
      development of agrin-deficient mice in which perinatal death was prevented by
      transgenic expression of neural agrin in motor neurons. Such transgenic, agrin
      deficient mice were born at Mendelian ratio but exhibited severe postnatal growth
      retardation. Growth plate morpholgy was markedly altered in these mice, with
      changes being most prominent in the hypertrophic zone. Compression of this zone
      was not caused by reduced viability of hypertrophic chondrocytes, as no
      differences in the apoptosis rates could be observed. Furthermore, deposition of
      the major cartilage matrix components collagen type II and aggrecan was slightly
      reduced in these mice. Consistent with a role for agrin in skeletal development,
      we show for the first time that agrin is highly expressed by chondrocytes and
      localizes to the growth plate in wild-type mice. Our data show that agrin is
      expressed in cartilage and that it plays a critical role in normal skeletal
      growth.

PMID- 17186268
TI  - Phytophotodermatitis mimicking non-accidental injury or self-harm.

PMID- 17186265
TI  - Replication of segment-specific and intercalated cells in the mouse renal
      collecting system.
AB  - The renal collecting system (CS) is composed of segment-specific (SS) and
      intercalated (IC) cells. The latter comprise at least two subtypes (type A and
      non-type A IC). The origin and maintenance of cellular heterogeneity in the CS is
      unclear. Among other hypotheses, it was proposed that one subtype of IC cells
      represents a stem cell population from which all cell types in the CS may arise.
      In the present study, we tested this stem cell hypothesis for the adult kidney by
      assessing DNA synthesis as a marker for cell replication. SS and IC cells were
      identified by their characteristic expressions of sodium- (epithelial sodium
      channel, Na-K-ATPase), water- (aquaporin-2) and acid/base- (H+ -ATPase, anion
      exchanger AE1) transporting proteins. Immunostaining for bromodeoxyuridine (BrdU)
      and for the proliferating cell nuclear antigen (PCNA) was used to reveal DNA
      synthesis in CS epithelium. BrdU- and PCNA-immunostaining as well as mitotic
      figures were seen in all subtypes of CS cells. Dividing cells retained the cell
      type specific expression of marker molecules. Treatment of mice with bumetanide
      combined with a high oral salt intake, which increases the tubular salt load in
      the CS, profoundly increased the DNA-synthesis rate in SS and non-type A IC
      cells, but reduced it in type A IC cells. Thus, our data show that DNA synthesis
      and cell replication occur in each cell lineage of the CS and in differentiated
      cells. The replication rate in each cell type can be differently modulated by
      functional stimulation. Independent proliferation of each cell lineage might
      contribute to maintain the cellular heterogeneity of the CS of the adult kidney
      and may also add to the adaptation of the CS to altered functional requirements.

PMID- 17186269
TI  - Orbital cellulitis in children: a review of 17 cases in the UK.

PMID- 17186270
TI  - Pyogenic splenic abscess in an infant with serological evidence of cat scratch
      disease.

PMID- 17186271
TI  - Multicentric infantile myofibromatosis: two perinatal cases.
AB  - Infantile myofibromatosis, the most common fibrous tumor of infancy, occurs in
      solitary, multiple, and generalized forms, with similar histology but different
      clinicopathologic and prognostic implications. This entity is a mesenchymal
      disorder characterized by the proliferation of fibrous tumors in the skin,
      muscles, viscera, bones, and subcutaneous tissues. Visceral lesions are
      associated with significant morbidity and mortality, generally within the first
      few months of life. They lead to failure to thrive, to infection, hemorrhage, or
      to the obstruction of vital organs. We describe two cases of multicentric
      myofibromatosis with significant in utero lesional growth, resulting in one fetal
      demise and one post-natal demise. To the best of our knowledge, this is the first
      report of a fetal death secondary to infantile myofibromatosis.

PMID- 17186272
TI  - Global developmental delay in guanidionacetate methyltransferase deficiency:
      differences in formal testing and clinical observation.
AB  - Guanidinoacetate N-methyltransferase (GAMT) deficiency is a defect in the
      biosynthesis of creatine (Cr). So far, reports have not focused on the
      description of developmental abilities in this disorder. Here, we present the
      result of formal testing of developmental abilities in a GAMT-deficient patient.
      Our patient, a 3-year-old boy with GAMT deficiency, presented clinically with a
      severe language production delay and nearly normal nonverbal development.
      Treatment with oral Cr supplementation led to partial restoration of the cerebral
      Cr concentration and a clinically remarkable acceleration of language production
      development. In contrast to clinical observation, formal testing showed a rather
      harmonic developmental delay before therapy and a general improvement, but no
      specific acceleration of language development after therapy. From our case, we
      conclude that in GAMT deficiency language delay is not always more prominent than
      delays in other developmental areas. The discrepancy between the clinical
      impression and formal testing underscores the importance of applying standardized
      tests in children with developmental delays. Screening for Cr deficiency by
      metabolite analysis of body fluids or proton magnetic resonance spectroscopy of
      the brain deficiency should be considered in any child with global developmental
      delay/mental retardation lacking clues for an alternative etiology.

PMID- 17186273
TI  - Biological control of Rhipicephalus (Boophilus) annulatus by different strains of
      Metarhizium anisopliae, Beauveria bassiana and Lecanicillium psalliotae fungi.
AB  - Virulence of 11 native strains of entomopathogenic fungi; Metarhizium anisopliae
      (three strains), Beauveria bassiana (six strains) and Lecanicillium psalliotae
      (two strains) collected from different parts of Iran, were studied against
      different developmental stages of Rhipicephalus (Boophilus) annulatus. After the
      exposure of ticks to the fungal strains in different concentrations (i.e. 10(3),
      10(5), 10(7) conidia/ml), various parameters such as mortality rate and
      reproductive efficiency of engorged females, mortality of unfed tick larvae and
      eclosion percentage of infected eggs were evaluated to determine the fungal
      virulence. Based on the obtained results, five strains including M. anisopliae
      (IRAN 437 C and DEMI 001), B. bassiana (IRAN 403 C) and L. psalliotae (IRAN 468 C
      and IRAN 518 C) were found to be virulent to various stages of tick developmental
      cycle. Mortality rate of engorged females was found to be dose-dependent with
      regard to the conidial concentration used. Total mortality rates of 90-100%, 70%
      and 56.6% were observed for M. anisopliae (IRAN 437 C and DEMI 001), B. bassiana
      (IRAN 403 C) and L. psalliotae (IRAN 468 C), 6-11 days post inoculation (PI) with
      10(7) conidia/ml, respectively. Most strains were able to inhibit egg laying by
      females in the range of 0-26% in different conidial concentrations. The results
      indicated that the mean egg laying of treated engorged tick females exposed to M.
      anisopliae (IRAN 437 C) was less than the mean values of those treated with other
      fungal strains. Results revealed 89.1%, 35.5% and 56.3% decrease in egg
      hatchability and 88.69%, 78.15% and 59.74% reduction in reproductive efficiency
      of the ticks using 10(7) conidia/ml of M. anisopliae (IRAN 437 C), B. bassiana
      (IRAN 403 C) and L. psalliotae (IRAN 468 C), respectively. In general, the
      entomopathogenic effects of native M. anisopliae and B. bassiana against various
      developmental stages of R. (B.) annulatus were confirmed in the present work.
      Likewise, although L. psalliotae, which was introduced for the first time as an
      entomopathogenic fungus against tick had not more than 13.3% mortality effect
      against adult females, but its effect on egg hatchability and reproductive
      efficiency was remarkable.

PMID- 17186274
TI  - Pro-oxidant effects of Mebendazole in albino rats experimentally infected with
      Trichinella spiralis.
AB  - Trichinellosis treated with Mebendazole often leads to complications in the
      course of the disease in humans and animals as a result of intoxication and hyper
      sensitization of an organism due to the massive destruction of parasites. This
      study was conducted to research Mebendazole incidence on lipid peroxidation
      processes (LPP) in rats' blood in Trichinella spiralis-infected and parasite-free
      albino rats. The research was conducted to evaluate erythrocyte superoxide
      dismutase (SOD) activity and malonic dialdehyde (MDA) concentration in blood
      serum. The parameters of the SOD-MDA system in infected albino rats, which were
      treated or untreated with Mebendazole were analyzed. It was concluded that
      Mebendazole amplifies the LPP in the blood of both infected and parasite-free
      animals: in a dose of 150 mg/kg anthelmintic causes disturbances of biochemical
      homeostasis in the SOD-MDA system, thus working as a pro-oxidant.

PMID- 17186275
TI  - Survey for the presence of specific free-living amoebae in cooling waters from
      Belgian power plants.
AB  - Free-living amoebae (FLA) are distributed ubiquitously in aquatic environments
      with increasing importance in hygienic, medical and ecological relationships to
      man. In this study, water samples from Belgian industrial cooling circuits were
      quantitatively surveyed for the presence of FLA. Isolated, thermotolerant amoebae
      were identified morphologically as well as using the following molecular methods:
      enzyme-linked immunosorbent assay and isoenzyme electrophoresis and PCR.
      Thermophilic amoebae were present at nearly all collection sites, and the
      different detection methods gave similar results. Naegleria fowleri was the most
      frequently encountered thermotolerant species, and concentrations of
      thermotolerant FLA were correlated with higher temperatures.

PMID- 17186276
TI  - Habitat complexity modifies ant-parasitoid interactions: implications for
      community dynamics and the role of disturbance.
AB  - Species must balance effective competition with avoidance of mortality imposed by
      predators or parasites to coexist within a local ecological community. Attributes
      of the habitat in which species interact, such as structural complexity, have the
      potential to affect how species balance competition and mortality by providing
      refuge from predators or parasites. Disturbance events such as fire can
      drastically alter habitat complexity and may be important modifiers of species
      interactions in communities. This study investigates whether the presence of
      habitat complexity in the form of leaf litter can alter interactions between the
      behaviorally dominant host ants Pheidole diversipilosa and Pheidole bicarinata,
      their respective specialist dipteran parasitoids (Phoridae: Apocephalus sp. 8 and
      Apocephalus sp. 25) and a single species of ant competitor (Dorymyrmex insanus).
      We used a factorial design to manipulate competition (presence/absence of
      competitors), mortality risk (presence/absence of parasitoids) and habitat
      complexity (presence/absence of leaf litter). Parasitoid presence reduced soldier
      caste foraging, but refuge from habitat complexity allowed increased soldier
      foraging in comparison to treatments in which no refuge was available. Variation
      in soldier foraging behavior correlated strongly with foraging success, a proxy
      for colony fitness. Habitat complexity allowed both host species to balance
      competitive success with mortality avoidance. The effect of fire on habitat
      complexity was also studied, and demonstrated that the immediate negative impact
      of fire on habitat complexity can persist for multiple years. Our findings
      indicate that habitat complexity can increase dominant host competitive success
      even in the presence of parasitoids, which may have consequences for coexistence
      of subordinate competitors and community diversity in general.

PMID- 17186278
TI  - Transient severe metastatic calcification in acute renal failure.
AB  - Metastatic calcification, a known complication of prolonged end-stage renal
      disease, is herein described for the first time in a 10-month-old boy with acute
      renal failure, manifesting as a painful and swollen arm. Imaging revealed diffuse
      calcification and technetium-99 methylene diphosphonate (99Tc-MDP) uptake around
      the humerus and axilla. Calcium and vitamin D restriction, followed by
      intravenous administration of sodium thiosulfate caused a full symptomatic, radio
      and scintigraphic improvement.

PMID- 17186277
TI  - Determining biological tissue turnover using stable isotopes: the reaction
      progress variable.
AB  - The reaction progress variable is applied to stable isotope turnover of
      biological tissues. This approach has the advantage of readily determining
      whether more than one isotope turnover pool is present; in addition, the
      normalization process inherent to the model means that multiple experiments can
      be considered together although the initial and final isotope compositions are
      different. Consideration of multiple isotope turnover pools allows calculation of
      diet histories of animals using a time sequence of isotope measurements along
      with isotope turnover pools. The delayed release of blood cells from bone marrow
      during a diet turnover experiment can be quantified using this approach. Turnover
      pools can also be corrected for increasing mass during an experiment, such as
      when the animals are actively growing. Previous growth models have been for
      exponential growth; the approach here can be used for several different growth
      models.

PMID- 17186279
TI  - Amelioration of steroids and cyclosporine-resistant nephrotic syndrome by
      pravastatin.
AB  - We report the case of a girl with steroids and cyclosporine (CsA) resistant focal
      segmental glomerulosclerosis (FSGS) whose proteinuria and hypoproteinaemia were
      dramatically resolved by pravastatin. She had been in a nephrotic condition for 6
      years. Prednisolone, pulse methylprednisolone therapy, low-density lipoprotein
      (LDL) apheresis, CsA, cyclophosphamide and mizoribine (MZR) had proved to be
      ineffective. She was started on pravastatin for her hyperlipidaemia 6 and a half
      years from onset, in addition to the baseline therapy, which included CsA;
      remission of the nephrotic syndrome was unexpectedly attained after 10 months of
      treatment. The baseline therapy has not been changed since the inclusion of
      pravastatin. This case suggests that, in patients with hyperlipidaemia, the
      response to CsA could be restored by lowering cholesterol levels with statins.
      The decrease of cholesterol levels might have improved the pharmacokinetics of
      CsA in this patient. Furthermore, the anti-inflammatory and immuno-modulatory
      effects, recently attributed to statins, may also have been involved in the
      improvement experienced by our patient.

PMID- 17186280
TI  - Recurrence of nephrotic syndrome/focal segmental glomerulosclerosis following
      renal transplantation in children.
AB  - The incidence of recurrence of nephrotic syndrome/focal segmental
      glomerulosclerosis (NS/FSGS) is variable (~30%). The incidence of recurrence is
      less in African-Americans than in whites and Hispanics. Graft survival rates are
      decreased in recipients with FSGS, especially if remission of the NS is not
      achieved in those with recurrence. Although controversial, the use of living
      donor (LD) transplants are not contraindicated; however, obligatory heterozygote
      parental grafts with a podocin mutation should be used with caution. Optimal
      treatment to induce a remission post-transplant has not been delineated. Pre
      transplant and/or prophylactic post-transplant pre-operative plasmapheresis (PP)
      for high-risk patients--especially those with recurrence in a previous graft--may
      be promising. An international multicenter controlled study is required to
      delineate the optimal approach to prevent and/or treat the recurrence of NS/FSGS.

PMID- 17186281
TI  - Small-scale spatial heterogeneity of arbuscular mycorrhizal fungal abundance and
      community composition in a wetland plant community.
AB  - Although it has become increasingly clear that arbuscular mycorrhizal fungi (AMF)
      play important roles in population, community, and ecosystem ecology, there is
      limited information on the spatial structure of the community composition of AMF
      in the field. We assessed small-scale spatial variation in the abundance and
      molecular diversity of AMF in a calcareous fen, where strong underlying
      environmental gradients such as depth to water table may influence AMF.
      Throughout an intensively sampled 2 x 2 m plot, we assessed AMF inoculum
      potential at a depth of 0-6 and 6-12 cm and molecular diversity of the AMF
      community using terminal restriction fragment length polymorphism of 18S rDNA.
      Inoculum potential was only significantly spatially autocorrelated at a depth of
      6-12 cm and was significantly positively correlated with depth to water table at
      both depths. Molecular diversity of the AMF community was highly variable within
      the plot, ranging from 2-14 terminal restriction fragments (T-RFs) per core, but
      the number of T-RFs did not relate to water table or plant species richness.
      Plant community composition was spatially autocorrelated at small scales, but AMF
      community composition showed no significant spatial autocorrelation. Saturated
      soils of calcareous fens contain many infective AMF propagules and the abundance
      and diversity of AMF inoculum is patchy over small spatial scales.

PMID- 17186282
TI  - Substantial sick-leave costs savings due to a graded activity intervention for
      workers with non-specific sub-acute low back pain.
AB  - The objective of this study is to compare the costs and benefits of a graded
      activity (GA) intervention to usual care (UC) for sick-listed workers with non
      specific low back pain (LBP). The study is a single-blind, randomized controlled
      trial with 3-year follow-up. A total of 134 (126 men and 8 women) predominantly
      blue-collar workers, sick-listed due to LBP were recruited and randomly assigned
      to either GA (N = 67; mean age 39 +/- 9 years) or to UC (N = 67; mean age 37 +/-
      8 years). The main outcome measures were the costs of health care utilization
      during the first follow-up year and the costs of productivity loss during the
      second and the third follow-up year. At the end of the first follow-up year an
      average investment for the GA intervention of 475 euros per worker, only 83 euros
      more than health care utilization costs in UC group, yielded an average savings
      of at least 999 euros (95% CI: -1,073; 3,115) due to a reduction in productivity
      loss. The potential cumulative savings were an average of 1,661 euros (95% CI: 
      4,154; 6,913) per worker over a 3-year follow-up period. It may be concluded that
      the GA intervention for non-specific LBP is a cost-beneficial return-to-work
      intervention.

PMID- 17186284
TI  - A hydrogen peroxide biosensor based on the direct electrochemistry of hemoglobin
      modified with quantum dots.
AB  - Direct electron transfer of hemoglobin modified with quantum dots (QDs) (CdS) has
      been performed at a normal graphite electrode. The response current is linearly
      dependent on the scan rate, indicating the direct electrochemistry of hemoglobin
      in that case is a surface-controlled electrode process. UV-vis spectra suggest
      that the conformation of hemoglobin modified with CdS is little different from
      that of hemoglobin alone, and the conformation changes reversibly in the pH range
      3.0-10.0. The hemoglobin in a QD film can retain its bioactivity and the modified
      electrode can work as a hydrogen peroxide biosensor because of its peroxidase
      like activity. This biosensor shows an excellent response to the reduction of
      H2O2 without the aid of an electron mediator. The catalytic current shows a
      linear dependence on the concentration of H2O2 in the range 5x10(-7)-3x10(-4) M
      with a detection limit of 6x10(-8) M. The response shows Michaelis-Menten
      behavior at higher H2O2 concentrations and the apparent Michaelis-Menten constant
      is estimated to be 112 microM.

PMID- 17186285
TI  - [Recent aspects in Meniere's disease].

PMID- 17186286
TI  - The effect of melatonin on endotoxemia-induced intestinal apoptosis and oxidative
      stress in infant rats.
AB  - OBJECTIVE: To evaluate the effect of melatonin on the intestinal apoptosis along
      with oxidative damage in endotoxemic infant rats. DESIGN AND SETTING: Prospective
      animal study in a university-based experimental research laboratory. SUBJECTS AND
      INTERVENTIONS: Wistar albino 7-day-old rat pups (n=21). The animals were
      randomized into three experimental groups: (1) controls; (2) endotoxemia; (3)
      endotoxemia treated with melatonin (10mg/kg). Endotoxemia was induced in rats by
      intraperitoneal injection of lipopolysaccharide (Escherichia coli serotype
      0111:B4; 3 mg/kg). MEASUREMENTS AND RESULTS: Four hours after LPS injection, the
      antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione
      peroxidase (GPx), and thiobarbituric acid reactive substance (TBARS) levels as an
      indicator of lipid peroxidation, were determined. Intestinal apoptosis was
      assessed by hematoxylin-eosin staining and terminal deoxynucleotide transferase
      mediated fluorescein-dUTP nick end labeling. The administration of melatonin into
      endotoxemic rats prevented the increase in the TBARS levels, and increased the
      activities of antioxidant enzymes and attenuated apoptotic cell death in both
      intestinal epithelium and lamina propria. CONCLUSIONS: Melatonin diminished the
      intestinal oxidative stress and apoptotic damage induced by endotoxemia in infant
      rats.

PMID- 17186288
TI  - Shock during heparin-induced thrombocytopenia: look for adrenal insufficiency!

PMID- 17186287
TI  - Pituitary-adrenal responses to human corticotropin-releasing hormone in
      critically ill patients.
AB  - OBJECTIVE: To investigate the pattern of pituitary-adrenal responses to human
      corticotropin-releasing hormone (hCRH) in critically ill patients and to examine
      the relation between responses and clinical outcome. DESIGN AND SETTING:
      Prospective study in consecutive critically ill patients in a general intensive
      care unit in a teaching hospital. PATIENTS: The study included 37 critically ill,
      mechanically ventilated patients with diverse underlying diagnoses (28 men, 9
      women; median age 56 years). INTERVENTIONS: A morning blood sample was obtained
      to measure baseline cortisol, corticotropin (ACTH), and cytokines. Patients were
      then injected with 100 microg hCRH, and plasma cortisol and ACTH were measured
      over a period of 2 h. MEASUREMENTS AND RESULTS: In the overall patient population
      baseline and peak cortisol concentrations following hCRH were 16+/-5 and 21+/-5
      microg/dl, respectively, and median baseline and peak ACTH levels 23 and 65
      pg/ml, respectively. Higher ACTH levels and longer release of cortisol were noted
      in nonsurvivors (n=18) than in survivors (n=19). Furthermore, nonsurvivors had
      higher concentrations of interleukin 8 (115 vs. 38 pg/ml) and interleukin 6 (200
      vs. 128 pg/ml) than survivors. CONCLUSIONS: Critically ill patients demonstrate
      altered pituitary-adrenal axis responses to hCRH. This is particularly evident in
      the sickest patients with the highest degree of inflammatory profile who
      ultimately do not survive.

PMID- 17186289
TI  - Assessment of CD4+ T cells specific for the tumor antigen SSX-1 in cancer-free
      individuals.
AB  - Proteins encoded by genes of the SSX family are specifically expressed in tumors
      and are therefore relevant targets for cancer immunotherapy. One of the first
      identified family members, SSX-1, is expressed in a large fraction of synovial
      sarcomas as a fusion protein together with the product of the SYT gene. In
      addition, the full-length SSX-1 antigen is frequently expressed in tumors of
      several other histological types such as sarcoma, melanoma, hepatocellular
      carcinoma, ovarian cancer and myeloma. To date, however, SSX-1 specific T cell
      responses have not been investigated and no SSX-1 derived T cell epitopes have
      been described. Here, we have assessed the presence of CD4(+) T cells directed
      against the SSX-1 antigen in circulating lymphocytes of cancer-free individuals.
      After a single in vitro stimulation with a pool of peptides spanning the entire
      SSX-1 protein we could detect and isolate SSX-1-specific CD4(+) T cells from 5/5
      donors analyzed. SSX-1-specific polyclonal populations isolated from these
      cultures recognized peptides located in three distinct regions of the protein
      containing clusters of sequences with significant predicted binding to frequently
      expressed MHC class II alleles. Characterization of specific clonal CD4(+) T cell
      populations derived from one donor allowed the identification of several
      naturally processed epitopes recognized in association with HLA-DR. These data
      document the existence of a significant repertoire of CD4(+) T cells specific for
      SSX-1 derived sequences in circulating lymphocytes of any individual that can be
      exploited for the development of both passive and active immunotherapeutic
      approaches to control disease evolution in cancer patients.

PMID- 17186290
TI  - Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and
      postoperative prognosis in human urothelial cancers.
AB  - PURPOSE: The programmed death-1 (PD-1)/B7-H1 (also called PD-L1) pathway
      negatively regulates T cell activation and has been suggested to play an
      important role in regulating antitumor host immunity. To investigate the clinical
      significance of B7-H1 expression to the tumor grade and postoperative prognosis
      of patients with urothelial cancer, we analyzed the relationship between B7-H1
      expression and various clinicopathological features and postoperative prognosis.
      EXPERIMENTAL DESIGN: Sixty-five urothelial cancer cases were examined. B7-H1
      expression in tumors and the numbers and phenotypes of tumor-infiltrating
      lymphocytes were evaluated by immunohistochemistry and flow cytometry. RESULTS: A
      substantial expression of B7-H1 was observed in all urothelial cancers
      investigated. Tumor specimens from patients with higher WHO grade or primary
      tumor classifications showed significantly higher percentages of tumor-associated
      B7-H1. Tumor-associated B7-H1 expression was significantly associated with a high
      frequency of postoperative recurrence and poor survival rate. Furthermore,
      multivariate analysis indicated that tumor-associated B7-H1 was more significant
      prognostic factor than WHO grade. CONCLUSIONS: Our results demonstrate that the
      aberrant expression of B7-H1 in urothelial cancer is associated with aggressive
      tumors, suggesting a regulatory role of tumor-associated B7-H1 in antitumor
      immunity. Therefore, the manipulation of tumor-associated B7-H1 may become a
      beneficial target for immunotherapy in human urothelial cancer.

PMID- 17186291
TI  - A DNA vaccine against chimeric AFP enhanced by HSP70 suppresses growth of
      hepatocellular carcinoma.
AB  - Alpha-fetoprotein (AFP) is produced principally in fetal liver, gastrointestinal
      tract and the yolk sac which is temporarily present during embryonic development.
      AFP is overexpressed in the majority of hepatocellular carcinoma (HCC) and thus
      offers an attractive target for immunotherapy against this neoplasm. Here, we
      report that anti-HCC effects were achieved in a therapeutic setting with a DNA
      vaccine encoding mouse AFP and co-expressing heat shock protein 70 (HSP70) gene.
      We also demonstrated that this vaccine elicited a marked and highly effective AFP
      specific CTL response against AFP-positive target cells. This vaccine also
      induced the prolongation of life span in mice bearing the tumor and the
      eradication of HCC. It is anticipated that vaccine strategies such as this may
      contribute to the effective future treatment of hepatocellular carcinoma.

PMID- 17186292
TI  - Unilateral weak radial pulse in a patient with systemic sclerosis: Takayasu's
      arteritis or thoracic outlet syndrome?

PMID- 17186293
TI  - Proximal humeral internal locking system (PHILOS) for the treatment of proximal
      humeral fractures.
AB  - INTRODUCTION: The aim of this study was to describe early results of a new
      internal locking system, PHILOS, used for the treatment of proximal humeral
      fractures. MATERIALS AND METHODS: A chart and radiographic review of 25 cases
      that had proximal humeral internal locking system (PHILOS) plate for the
      treatment of proximal humeral fractures was performed. RESULTS: Of the 25 cases,
      20 went to union with a mean neck/shaft angle of 127.2 degrees . Five cases
      required or were considered for revision surgery for non-union or implant
      failure. Of the 25 implants, 4 had screw protrusion into the gleno-humeral joint,
      4 had screw loosening and backing out, and 1 plate broke without further trauma.
      CONCLUSIONS: Our results suggest that PHILOS is an effective system for providing
      fracture stabilisation to bony union but awareness of potential hardware
      complications is essential.

PMID- 17186294
TI  - Hungarian mtDNA population databases from Budapest and the Baranya county Roma.
AB  - To facilitate forensic mtDNA testing in Hungary, we have generated control region
      databases for two Hungarian populations: 211 individuals were sampled from the
      urban Budapest population and 208 individuals were sampled from a Romani
      ("gypsy") population in Baranya county. Sequences were generated using a highly
      redundant approach to minimize potential database errors. The Budapest population
      had high sequence diversity with 180 lineages, 183 polymorphic positions, and a
      random match probability of 1%. In contrast, the Romani population exhibited low
      sequence diversity, with only 56 lineages, 109 segregating sites, and a random
      match probability of 8.8%. The mtDNA haplogroup compositions of the two
      populations were also distinct, with the large proportion of haplogroup M samples
      (35%) in the Roma the most obvious difference between the two populations. These
      factors highlight the importance of considering population structure when
      generating reference databases for forensic testing purposes. Comparisons between
      our Romani population sample and other published data indicate the need for
      heightened caution when sampling and using mtDNA databases of small endogamous
      populations. The Romani populations that we compared showed significant
      departures from genetic uniformity.

PMID- 17186295
TI  - Reduced plasma free fatty acid availability during exercise: effect on gene
      expression.
AB  - Endurance exercise transiently increases the mRNA of key regulatory proteins
      involved in skeletal muscle metabolism. During prolonged exercise and subsequent
      recovery, circulating plasma fatty acid (FA) concentrations are elevated. The
      present study therefore aimed to determine the sensitivity of key metabolic genes
      to FA exposure, assessed in vitro using L6 myocytes and secondly, to measure the
      expression of these same set of genes in vivo, following a single exercise bout
      when the post-exercise rise in plasma FA is abolished by acipimox. Initial
      studies using L6 myotubes demonstrated dose responsive sensitivity for both PDK4
      and PGC-1alpha mRNA to acute FA exposure in vitro. Nine active males performed
      two trials consisting of 2 h exercise, followed by 2 h of recovery. In one trial,
      plasma FA availability was reduced by the administration of acipimox (LFA), a
      pharmacological inhibitor of adipose tissue lipolysis, and in the second trial a
      placebo was provided (CON). During the exercise bout and during recovery, the
      rise in plasma FA and glycerol was abolished by acipimox treatment. Following
      exercise the mRNA abundance of PDK4 and PGC-1alpha were elevated and unaffected
      by either acipimox or placebo. Further analysis of skeletal muscle gene
      expression demonstrated that the CPT I gene was suppressed in both trials, whilst
      UCP-3 gene was only modestly regulated by exercise alone. Acipimox ingestion did
      not alter the response for both CPT I and UCP-3. Thus, this study demonstrates
      that the normal increase in circulating concentrations of FA during the later
      stages of exercise and subsequent recovery is not required to induce skeletal
      muscle mRNA expression of several proteins involved in regulating substrate
      metabolism.

PMID- 17186296
TI  - Effects of age on ventilatory threshold and peak oxygen uptake normalised for
      regional skeletal muscle mass in Japanese men and women aged 20-80 years.
AB  - Ventilatory threshold (VT) is an important predictor of cardiorespiratory
      fitness, such as peak oxygen uptake (VO2peak) and is a valuable index of aerobic
      exercise intensity. However, little is known about the role of skeletal muscle
      (SM) mass in the age-associated decline of VT. Therefore, the present study was
      performed to investigate the effects of age on cardiopulmonary fitness normalised
      for regional SM mass in 1,463 Japanese men and women, and to determine the
      relevance of VT normalised to SM mass based on age and gender. Total, trunk and
      thigh SM mass were measured using an ultrasound method, while VO2peak and VT were
      determined during treadmill walking. VO2peak was estimated using the predicted
      maximum heart rate (HR) and the HR-VO2 relationship for sub-maximal treadmill
      walking. There were significant negative correlations between VT normalised for
      body mass and age in men and women (P < 0.001). Age-associated declines were also
      observed in VT normalised for body mass in both men and women; however, VT
      normalised for SM mass was not significantly different with age. Significant
      correlations were also observed between thigh SM mass and VT in both men and
      women. These results suggest that thigh SM mass is closely associated with
      VO2peak and/or VT in both men and women, and the decrease in VT with age is
      predominantly due to an age-related decline of SM mass. Moreover, this study
      provides normative cardiorespiratory fitness data regarding VT normalised SM mass
      in healthy men and women aged 20-80 years.

PMID- 17186297
TI  - Insights into central and peripheral factors affecting the "oxidative
      performance" of skeletal muscle in aging.
AB  - During exercises with relatively small muscle masses, limitations to exercise
      performance by the cardiovascular system should be significantly reduced,
      allowing one to fully-test the "oxidative potential" of the investigated muscles.
      Ten elderly males (E, 77.8 +/- 2.9 years [x +/- SD]) and eight young controls (Y,
      26.6 +/- 3.0) underwent incremental exercises to voluntary exhaustion on a
      dynamic leg-extension (dominant limb) machine (knee-extension, KE) and on a
      cycloergometer (CYCLO). During KE the load was increased every 3 min to loads
      corresponding to 20, 40 and 60% of the force of one-repetition maximum (1RM). The
      following variables were determined (vastus lateralis muscle): concentration
      changes of deoxygenated haemoglobin and myoglobin (Delta[deoxy(Hb + Mb)]) by near
      infrared spectroscopy (NIRS), expressed as percentage of the maximal value
      obtained during transient limb ischemia, and taken as an index of O2 extraction;
      root mean square (RMS) and median power frequency (MDF) by electromyography. The
      total lifted load during KE and peak workload during CYCLO were lower in E versus
      Y (620.4 +/- 321.9 kg vs. 1347.4 +/- 458.7; 113.5 +/- 23.9 W vs. 224.3 +/- 41.0,
      respectively). During CYCLO Delta[deoxy(Hb + Mb)] peak (i.e. the value determined
      at exhaustion) was lower in E (44.5 +/- 17.7%) versus Y (67.1 +/- 22.9), whereas
      during KE Delta[deoxy(Hb + Mb)] peak was higher in E (56.8 +/- 20.9%) versus Y
      (38.6 +/- 15.8). "Thresholds", that is abrupt increases in RMS slopes, were
      detected in Y but not in E, suggesting less recruitment or a preferential atrophy
      of type 2 fibers in the elderly. These findings, associated with the preserved
      capacity of O2 extraction, suggest a shift towards oxidative metabolism in
      skeletal muscles of 78 year-old subjects, which could preserve, at least in part,
      their capacity to carry out exercise.

PMID- 17186298
TI  - Plasma ghrelin responses to acute sculling exercises in elite male rowers.
AB  - The regulatory effect of ghrelin on growth hormone (GH) is limited in describing
      ghrelin response to acute submaximal exercise intensities in elite athletes. We
      investigated the effects of a single sculling exercise performed above and below
      the individual anaerobic threshold (IAT) on total ghrelin concentration in highly
      trained male rowers. Nine elite male rowers (20.1 +/- 3.7 years; 190.0 +/- 5.2
      cm; 89.6 +/- 4.6 kg; %body fat: 9.9 +/- 2.5%) volunteered for this study. Single
      scull rowing was performed below and above IAT using a mean of 5 bpm above and
      below the heart rate of the IAT during graded exercise test. Ghrelin, leptin, GH,
      insulin, and glucose were measured before, immediately after, and after 30 min of
      recovery. Plasma ghrelin concentration did not increase significantly in either
      exercise but was approaching significance after 30 min of recovery (P = 0.051)
      when the constant load sculling was performed at the intensity above the IAT.
      There were no changes in plasma leptin levels. GH increased significantly
      immediately after exercise and remained elevated during the 30 min of recovery in
      both exercise conditions, while insulin decreased significantly immediately after
      exercise and remained significantly lower after the 30 min of recovery in both
      exercise intensities. Baseline ghrelin was not correlated with the body
      composition, physical performance, or blood biochemical data. There was no
      significant relationship between plasma ghrelin and other blood variables
      immediately after the 30 min of recovery in both exercise tests and changes in
      ghrelin were not related to blood biochemical variables after the exercise tests.
      The acute constant load sculling exercise above or below IAT that increased GH
      concentrations did not significantly increase the circulating plasma ghrelin
      levels.

PMID- 17186299
TI  - The influence of inspiratory and expiratory muscle training upon rowing
      performance.
AB  - We investigated the effect of 4 week of inspiratory (IMT) or expiratory muscle
      training (EMT), as well as the effect of a subsequent 6 week period of combined
      IMT/EMT on rowing performance in club-level oarsmen. Seventeen male rowers were
      allocated to either an IMT (n = 10) or EMT (n = 7) group. The groups underwent a
      4 week IMT or EMT program; after interim testing, both groups subsequently
      performed a 6 week program of combined IMT/EMT. Exercise performance and
      physiological responses to exercise were measured at 4 and 10 week during an
      incremental rowing ergometer 'step-test' and a 6 min all-out (6MAO) effort.
      Pressure threshold respiratory muscle training was undertaken at the 30
      repetition maximum load (approximately 50% of the peak inspiratory and expiratory
      mouth pressure, P (Imax) or P (Emax), respectively). P (Imax) increased during
      the IMT phase of the training in the IMT group (26%, P < 0.001) and was
      accompanied by an improvement in mean power during the 6MAO (2.7%, P = 0.015).
      Despite an increase in P (Emax) by the end of the intervention (31%, P = 0.03),
      the EMT group showed no significant changes in any performance parameters during
      either the 'step-test' or 6MAO. There were no significant changes in breathing
      pattern or the metabolic response to the 6MAO test in either group, but the IMT
      group showed a small decrease in HR (2-5%, P = 0.001). We conclude that there
      were no significant additional changes following combined IMT/EMT. IMT improved
      rowing performance, but EMT and subsequent combined IMT/EMT did not.

PMID- 17186300
TI  - A stretching program increases the dynamic passive length and passive resistive
      properties of the calf muscle-tendon unit of unconditioned younger women.
AB  - This study examined the effects of a 6-week stretching program on the dynamic
      passive elastic properties of the calf muscle-tendon unit (MTU) of unconditioned
      younger women. After random assignment of 12 women (age 18-31 years) to a
      stretching group (SG) or to a control group (CG), six subjects in the SG and four
      subjects in the CG completed the study. For the initial tests, a Kin-Com
      dynamometer moved the ankle from plantarflexion to maximal dorsiflexion (DF) with
      negligible surface EMG activity in the soleus, gastrocnemius and tibialis
      anterior muscles. Angular displacement, passive resistive torque, area under the
      curve (passive elastic energy) and stiffness variables were reduced from the
      passive DF torque curves. The SG then completed ten static wall stretches held 15
      s each, five times a week for 6 weeks, the CG did not. The tests were repeated
      and the changes between the tests and retests were examined for group differences
      (Mann-Whitney U). The SG had significant increases in the maximal passive DF
      angle (7 degrees +/- 4 degrees ), maximal passive DF torque (11.2 +/- 8.3 N m),
      full stretch range of motion (23 degrees +/- 24 degrees ), full stretch mean
      torque (3.4 +/- 2.1 N m), and area under the full stretch curve (22.7 +/- 23.5
      degrees N m) compared to the CG (P < or = 0.019). The passive stiffness did not
      change significantly. The results showed that a stretching program for
      unconditioned calf MTUs increased the maximal DF angle and length extensibility,
      as well as the passive resistive properties throughout the full stretch range of
      motion. The adaptations within the calf MTU provide evidence that stretching
      enhances the dynamic passive length and passive resistive properties in
      unconditioned younger women.

PMID- 17186301
TI  - The shift in muscle's length-tension relation after exercise attributed to
      increased series compliance.
AB  - Eccentric exercise can produce damage to muscle fibres. Here damage indicators
      are measured in the medial gastrocnemius muscle of the anaesthetised cat after
      eccentric contractions on the descending limb of the muscle's length-tension
      relation, compared with eccentric contractions on the ascending limb and
      concentric contractions on the descending limb. One damage indicator is a shift
      of the optimum length for peak active tension, in the direction of longer muscle
      lengths. The shift has been attributed to an increase in muscle compliance. It is
      a corollary of a current theory for the mechanism of the damage. With the
      intention of seeking further support for the theory, in these experiments we test
      the idea that other damage indicators, specifically the fall in twitch:tetanus
      ratio and in muscle force are due, in part, to such an increase in compliance.
      This was tested in an undamaged muscle by insertion of a compliant spring (0.19
      mm N(-1)) in series with the muscle. This led to a fall in tetanic tension by
      17%, a shift in optimum length of 1.7 mm in the direction of longer muscle
      lengths and a fall in twitch tetanus ratio by 15%. The fall in tension is
      postulated to be due to development of non-uniform sarcomere lengths within
      muscle fibres. It is concluded that after a series of eccentric contractions of a
      muscle, the fall in force is the result of a number of interdependent factors,
      not all of which are a direct consequence of the damage process.

PMID- 17186302
TI  - Performance predicting factors in prolonged exhausting exercise of varying
      intensity.
AB  - Several endurance sports, e.g. road cycling, have a varying intensity profile
      during competition. At present, few laboratory tests take this intensity profile
      into consideration. Thus, the purpose of this study was to examine the prognostic
      value of heart rate (HR), lactate (La(-1)), potassium (K(+)), and respiratory
      exchange ratio (RER) performance at an exhausting cycling exercise with varying
      intensity. Eight national level cyclists performed two cycle tests each on a
      cycle ergometer: (1) a incremental test to establish VO(2max), maximum power (W
      (max)), and lactate threshold (VO(2LT)), and (2) a variable intensity protocol
      (VIP). Exercise intensity for the VIP was based upon the VO(2max) obtained during
      the incremental test. The VIP consisted of six high intense (HI) workloads at 90%
      of VO(2max) for 3 min each, interspersed by five middle intense (MI) workloads at
      70% of VO(2max )for 6 min each. VO(2 )and HR were continuously measured
      throughout the tests. Venous blood samples were taken before, during, and after
      the test. Increases in HR, La(-), K(+), and RER were observed when workload
      changed from MI to HI workload (P < 0.05). Potassium and RER decreased after
      transition from HI to MI workloads (P < 0.05). There was a negative correlation
      between time to exhaustion and decrease in La(-) concentration during the first
      MI (r = -0.714; P = 0.047). Furthermore, time to exhaustion correlated with
      VO(2LT )calculated from the ramp test (r = 0.738; P = 0.037). Our results suggest
      that the magnitude of decrease of La(-1) between the first HI workload and the
      consecutive MI workload could predict performance during prolonged exercise with
      variable intensity.

PMID- 17186303
TI  - Hand-grip strength of young men, women and highly trained female athletes.
AB  - Hand-grip strength has been identified as one limiting factor for manual lifting
      and carrying loads. To obtain epidemiologically relevant hand-grip strength data
      for pre-employment screening, we determined maximal isometric hand-grip strength
      in 1,654 healthy men and 533 healthy women aged 20-25 years. Moreover, to assess
      the potential margins for improvement in hand-grip strength of women by training,
      we studied 60 highly trained elite female athletes from sports known to require
      high hand-grip forces (judo, handball). Maximal isometric hand-grip force was
      recorded over 15 s using a handheld hand-grip ergometer. Biometric parameters
      included lean body mass (LBM) and hand dimensions. Mean maximal hand-grip
      strength showed the expected clear difference between men (541 N) and women (329
      N). Less expected was the gender related distribution of hand-grip strength: 90%
      of females produced less force than 95% of males. Though female athletes were
      significantly stronger (444 N) than their untrained female counterparts, this
      value corresponded to only the 25th percentile of the male subjects. Hand-grip
      strength was linearly correlated with LBM. Furthermore, both relative hand-grip
      strength parameters (F (max)/body weight and F (max)/LBM) did not show any
      correlation to hand dimensions. The present findings show that the differences in
      hand-grip strength of men and women are larger than previously reported. An
      appreciable difference still remains when using lean body mass as reference. The
      results of female national elite athletes even indicate that the strength level
      attainable by extremely high training will rarely surpass the 50th percentile of
      untrained or not specifically trained men.

PMID- 17186304
TI  - Nine months aerobic fitness induced changes on blood lipids and lipoproteins in
      untrained subjects versus controls.
AB  - Regular endurance exercise has favorable effects on cardiovascular risk factors.
      However, the impact of an exercise-induced change in aerobic fitness on blood
      lipids is often inconsistent. The purpose of this study was to investigate the
      effect of nine consecutive months of training on aerobic fitness and blood lipids
      in untrained adults. Thirty subjects 35-55 years of age (wt: 73.1 +/- 13.6 kg,
      height 171.1 +/- 9.0 cm, %body fat 24.6 +/- 6.3%, 14 males and 16 females) were
      randomly assigned to an exercise (EG) (N = 20) and control (CG) (N = 10) group.
      All subjects completed an incremental treadmill test, anthropometric
      measurements, and venous blood sample collection before and after the 9 months of
      exercise. Participants in the exercise group were supervised and adjusted for
      improvements in running performance, whereas no change was administered for the
      control group. One-way and multivariate ANOVA was conducted to determine
      significant differences in means for time and group in selected variables [body
      mass, % body fat, BMI; VO(2peak), km/h at 2.0 (v-LA2) and 4.0 (v-LA4) mmol l(-1)
      blood lactate (LA) concentration, km/h of the last load (v-max); TC, LDL-C, HDL
      C, TG, Apo B, Apo A-1, and Lp (a)]. Correlation coefficients and multivariate
      regression analysis was used to determine the association between aerobic fitness
      and blood lipids. The exercise group improved significantly (P < 0.0001) in
      VO(2peak), v-LA2, v-LA4, v-max and exhibited a significant decrease in Apo B (P <
      0.04) compared to the control group (NS). In 9 months, E achieved 24% increase in
      VO(2peak) and 18% reduction in Apo B, denoting the impact of cardiovascular
      fitness on cardiovascular risk.

PMID- 17186305
TI  - Hip, thigh and calf muscle atrophy and bone loss after 5-week bedrest inactivity.
AB  - Unloaded inactivity induces atrophy and functional deconditioning of skeletal
      muscle, especially in the lower extremities. Information is scarce, however,
      regarding the effect of unloaded inactivity on muscle size and function about the
      hip. Regional bone loss has been demonstrated in hips and knees of elderly
      orthopaedic patients, as quantified by computerized tomography (CT). This method
      remains to be validated in healthy individuals rendered inactive, including real
      or simulated weightlessness. In this study, ten healthy males were subjected to 5
      weeks of experimental bedrest and five matched individuals served as ambulatory
      controls. Maximum voluntary isometric hip and knee extension force were measured
      using the strain gauge technique. Cross-sectional area (CSA) of hip, thigh and
      calf muscles, and radiological density (RD) of the proximal tibial bone were
      measured using CT. Bedrest decreased (P < 0.05) average (SD) muscle strength by
      20 (8)% in knee extension, and by 22 (12)% in hip extension. Bedrest induced
      atrophy (P < 0.05) of extensor muscles in the gluteal region, thigh and calf,
      ranging from 2 to 12%. Atrophy was more pronounced in the knee extensors [9 (4)%]
      and ankle plantar flexors [12 (3)%] than in the gluteal extensor muscles [2
      (2)%]. Bone density of the proximal tibia decreased (P < 0.05) by 3 (2)% during
      bedrest. Control subjects did not show any temporal changes in muscle or bone
      indices (P > 0.05), when examined at similar time intervals. The present findings
      of a substantial loss in hip extensor strength and a smaller, yet significant
      atrophy of these muscles, demonstrate that hip muscle deconditioning accompanies
      losses in thigh and calf muscle mass after bedrest. This suggests that
      comprehensive quantitative studies on impaired locomotor function after
      inactivity should include all joints of the lower extremity. Our results also
      demonstrate that a decreased RD, indicating bone mineral loss, can be shown
      already after 5 weeks of unloaded bedrest, using a standard CT technique.

PMID- 17186308
TI  - The effects of time pressure on chess skill: an investigation into fast and slow
      processes underlying expert performance.
AB  - The ability to play chess is generally assumed to depend on two types of
      processes: slow processes such as search, and fast processes such as pattern
      recognition. It has been argued that an increase in time pressure during a game
      selectively hinders the ability to engage in slow processes. Here we study the
      effect of time pressure on expert chess performance in order to test the
      hypothesis that compared to weak players, strong players depend relatively
      heavily on fast processes. In the first study we examine the performance of
      players of various strengths at an online chess server, for games played under
      different time controls. In a second study we examine the effect of time controls
      on performance in world championship matches. Both studies consistently show that
      skill differences between players become less predictive of the game outcome as
      the time controls are tightened. This result indicates that slow processes are at
      least as important for strong players as they are for weak players. Our findings
      pose a challenge for current theorizing in the field of expertise and chess.

PMID- 17186306
TI  - Role of acid-sensitive outwardly rectifying anion channels in acidosis-induced
      cell death in human epithelial cells.
AB  - Recently, a novel type of anion channel activated by extracellular acidification
      has been found in a variety of mammalian cell types. However, the role of this
      acid-sensitive outwardly rectifying (ASOR) anion channel is not known. In human
      epithelial HeLa cells, reduction in extracellular pH below 5 rapidly activated
      anion-selective whole-cell currents. The currents exhibited strong outward
      rectification, activation kinetics at positive potentials, low-field anion
      selectivity, and sensitivity to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic
      acid (DIDS) and phloretin. When outside-out patches were exposed to acidic
      bathing solution, single-channel events of the anion channel could be observed.
      The unitary conductance was 4.8 pS in the voltage range between -80 and +80 mV.
      The single-channel activity prominently increased with depolarization and was
      suppressed by DIDS or phloretin. After 1-h incubation in acidic solution (pH
      4.5), a significant population of HeLa cells suffered from necrotic cell injury
      characterized by stainability with propidium iodide and lack of caspase-3
      activation. Upon exposure to acidic solution, HeLa cells exhibited immediate,
      persistent swelling. Both the necrotic volume increase and cell injury induced by
      extracellular acidification were inhibited by DIDS or phloretin. Therefore, it is
      concluded that the ASOR anion channel is involved in the genesis of necrotic cell
      injury induced by acidosis in human epithelial cells.

PMID- 17186309
TI  - Neutrophil depletion retards endometrial repair in a mouse model.
AB  - The contribution of the high abundance of inflammatory cells present in the human
      endometrium prior to and during menstruation is unknown with respect to
      endometrial repair and/or menstruation. In this study, the presence and
      localisation of markers for key inflammatory cells have been examined in a mouse
      model of endometrial breakdown and repair and the functional contribution of
      neutrophils has been determined. In the model, decidualisation is artificially
      induced and progesterone support withdrawn; the endometrial tissue progressively
      breaks down by 24 h after progesterone withdrawal and, by 48 h, has usually
      undergone complete repair. Neutrophils have been identified in low abundance in
      decidual tissue, rise in number during breakdown and are most abundant during
      early repair. Macrophages are barely detectable during breakdown or repair in
      this model, whereas uterine natural killer cells are found only in intact
      decidua. The functional contribution of neutrophils to endometrial breakdown and
      repair has been assessed via neutrophil depletion by using the antibody RB6-8C5.
      This antibody significantly depletes neutrophils from the circulation and tissue,
      affects endometrial breakdown and markedly delays endometrial repair. This study
      has therefore demonstrated that neutrophils are the most abundant leucocyte in
      this model and that they play an important functional role in the processes of
      endometrial breakdown and repair.

PMID- 17186307
TI  - Characterization of endogenous betaine gamma-amino-n-butyric acid cotransporter
      glycoform and its hyperosmotic regulation in MDCK cells.
AB  - Increase in mRNA expression and transport activity of the betaine gamma-amino-n
      butyric acid cotransporter (BGAT) in response to hyperosmolality has been
      previously shown in MDCK cells. However, the hyperosmolality-induced response of
      endogenous BGAT protein expression was not investigated in detail. We show two
      forms of endogenous BGAT immunoreactivity that are expressed in MDCK II cells.
      Both are sensitive to Peptide N-Glycosidase F (PNGase F), suggesting that they
      are N-glycosylated proteins. One band, about 75 kDa, is resistant to Endo H,
      while the other 55 kDa band is sensitive to it, suggesting that they are fully N
      glycosylated mature form in the post-Golgi compartment and core-glycosylated
      immature form in the endoplasmic reticulum (ER), respectively. When treated with
      hyperosmolality, they are significantly increased. But the rate of BGAT
      processing, as assessed by the ratio of mature to immature form, is not
      increased, suggesting that hyperosmolality does not facilitate the export of BGAT
      from the ER to the secretory pathway. Surface biotinylation and confocal
      microscopy show that hyperosmolality significantly increases the amount of the
      mature form of BGAT on the basolateral membrane with a very small fraction on the
      apical membrane. We conclude that BGAT is an N-glycosylated protein with two
      glycoforms and endogenous BGAT synthesis rather than processing is involved in
      the adaptation to the hyperosmotic stress.

PMID- 17186310
TI  - Iatrogenic injury to oral branches of the trigeminal nerve: records of 449 cases.
AB  - The aims of this study were threefold: (1) to describe iatrogenic lesions to oral
      branches of the trigeminal nerve, signs and symptoms, and functional status, (2)
      to report on a simple neurosensory examination method, and (3) to discuss means
      of prevention of iatrogenic injury. The etiology and functional status of 449
      injuries to oral branches collected over 18 years were retrospectively reviewed.
      A simple scheme of a clinical neurosensory examination was applied to enable a
      quantified rating of the perception. Injury to the lingual nerve (n = 261) is not
      only the most prevalent type of lesion, it also seems to be the most devastating
      type of lesion. Third molar surgery (n = 319) counts for the majority of injuries
      to the lingual, inferior alveolar, and buccal nerves. Lesions related to the
      injection of local analgesics was the second most frequent etiology (n = 78), and
      the lingual nerve was affected more frequently and severely than other oral
      branches of the trigeminal nerve. The female gender was overrepresented in
      incidence of injured nerves but no difference was found in the severity of
      affection between females and males. All grades of loss of neurosensory functions
      were found, and a range of neurogenic malfunctions was reported. Methodological
      obstacles in clinical neurosensory examination of trigeminal nerve injury and the
      magnitude of neurosensory impairment are discussed. Many nerve injuries are
      avoidable by critical reevaluation of indications, increased awareness of
      potential hazards, and modified surgical procedures.

PMID- 17186311
TI  - Characterizing intramural stress and inflammation in hypertensive arterial
      bifurcations.
AB  - A histology-based methodology was developed and used to determine whether
      intramural stress and combined monocyte/macrophage density positively correlate
      within hypertensive bifurcations. Hypertension was induced in Sprague-Dawley rats
      using Angiotensin II pumps. Analysis focused on mesenteric bifurcations harvested
      7 days (n = 4) post implant, but also included normotensive (n = 2) and 21-day
      hypertensive (n = 1) samples. Mesentery was processed in a manner that preserves
      morphology, corrects for histology-related distortions and results in
      reconstructions suitable for finite element analysis. Peaks in intramural stress
      and monocyte/macrophage density occurred near bifurcations after the onset of
      hypertension. Cell density peaks occurred in regions where surface curvature is
      complex and tends to heighten intramural stress. Also, a strong positive
      correlation between mean stress and mean cell density suggests that they are
      related phenomena. A point-by-point comparison of stress and cell density
      throughout each bifurcation did not exhibit a consistent pattern. We offer
      reasons why this most stringent test did not corroborate our other findings that
      high intramural stress is correlated with increased inflammation near the center
      of the bifurcation.

PMID- 17186313
TI  - Comments about "The hamate facet of the lunate: a radiographic study in an Arab
      population from Bahrain".

PMID- 17186314
TI  - The female inferior hypogastric (= pelvic) plexus: anatomical and radiological
      description of the plexus and its afferences--applications to pelvic surgery.
AB  - AIM OF THE STUDY: We wanted to determine the anatomical features of the inferior
      hypogastric plexus (IHP), and the useful landmarks for a safe surgical approach
      during pelvic surgery. MATERIALS AND METHODS: We dissected the IHP in 22
      formolized female anatomical subjects, none of which bore any stigmata of
      subumbilical surgery. RESULTS: The inferior hypogastric plexus (IHP) is a
      triangle with a posterior base and an anterior inferior top. It can be described
      as having three edges and three angles; its inferior edge stretches constantly
      from the fourth sacral root to the ureter's point of entry into the posterior
      layer of the broad ligament; its cranial edge is strictly parallel to the
      posterior edge of the hypogastric artery, along which it runs at a distance of 10
      mm; its posterior (dorsal) edge is at the point of contact with the sacral roots,
      from which it receives its afferences. They most frequently originate from S3 or
      S4 (60%) and then, in one or two branches, often from S2 (40%), never from S1 and
      in exceptional cases from S5 (20%). There are sympathetic afferences in 30% of
      cases, usually through a single branch of the second, third or fourth sacral
      ganglion. All IHPs have at least one sacral afference and sometimes there may be
      up to three afferences from the same sacral root. Its dorsal cranial angle, which
      is superior, comes after the SHP (hypogastric nerve or presacral nerve filament);
      its anterior inferior angle is located exactly at the ureter's point of entry
      into the posterior layer of the broad ligament. This is the top of the IHP; its
      posterior inferior angle is located at the point of contact with the fourth
      sacral root. At its entrance at the base of the parametrium the pelvic ureter is
      the anterior, fundamental positional reference for the IHP. The vaginal
      efferences come out of the top of the IHP through branches leading to the
      bladder, the vagina and the rectum, which originate through two trunks exactly
      underneath the crossing point of the ureter and the uterine artery: (i) one trunk
      leading to the bladder runs along and underneath the ureter and divides into two
      groups, which are lateral and medial, trigonal. (ii) the trunk leading to the
      vagina runs along the inferior edge of the uterine artery. At the point of
      contact with the lateral edge of the vagina, it splits into two groups: anterior
      thin and posterior voluminous. Some of its branches perforate the posterior wall
      of the vagina and are distributed to the rectovaginal septum in a tooth comb
      pattern. The inferior branches, which emerge from the inferior edge of the IHP,
      reach the rectum directly. The dissection of the 22 specimens allowed us to
      describe three efferent plexuses: a vaginal rectal plexus, a vesical plexus and a
      inferior rectal plexus. So the IHP's anterior, fundamental positional reference
      is the pelvic ureter at the point where it enters at the base of the parametrium,
      then at the crossing point of the uterine artery. The ureter is the vector for
      vesical efferences, the uterine artery is the vector for vaginal efferences,
      which are thus sent into the vesicovaginal septum and the rectovaginal septum.
      This surgical point of reference is of vital importance in nerve sparing during
      the course of a simple or extended hysterectomy. Any dissection carried out
      underneath and outside of the ureter inevitably carries a risk of lesions to its
      efferent, lateral vesical or medial, rectovaginal fibres.

PMID- 17186316
TI  - Interrelationships between Dunaliella and halophilic prokaryotes in saltern
      crystallizer ponds.
AB  - Thanks to their often very high population densities and their simple community
      structure, saltern crystallizer ponds form ideal sites to study the behavior of
      halophilic microorganisms in their natural environment at saturating salt
      concentrations. The microbial community is dominated by square red halophilic
      Archaea, recently isolated and described as Haloquadratum walsbyi, extremely
      halophilic red rod-shaped Bacteria of the genus Salinibacter, and the unicellular
      green alga Dunaliella as the primary producer. We review here, the information
      available on the microbial community structure of the saltern crystallizer brines
      and the interrelationships between the main components of their biota. As
      Dunaliella produces massive amounts of glycerol to provide osmotic stabilization,
      glycerol is often postulated to be the most important source of organic carbon
      for the heterotrophic prokaryotes in hypersaline ecosystems. We assess here, the
      current evidence for the possible importance of glycerol and other carbon sources
      in the nutrition of the Archaea and the Bacteria, the relative contribution of
      halophilic Bacteria and Archaea to the heterotrophic activity in the brines, and
      other factors that determine the nature of the microbial communities that thrive
      in the salt-saturated brines of saltern crystallizer ponds.

PMID- 17186317
TI  - Hereditary prosopagnosia (HPA): the first report outside the Caucasian
      population.
AB  - Prosopagnosia (PA) or face blindness is characterized by a deficiency in
      identifying familiar faces. Almost all reports are single cases or collections of
      unrelated patients who acquired prosopagnosia after brain injuries, strokes or
      atrophy of at least the right occipito-temporal cortex. Until 2001, the inborn
      form - in the absence of any brain lesions - was described in fewer than 20
      probands exclusively of Caucasian origin. We recently found that in the German
      Caucasian population, congenital prosopagnosia has a very high prevalence of at
      least 2.5% and that it is genetically determined. It is best described by
      autosomal-dominant inheritance in the more than 50 families investigated. We
      therefore introduced the term non-syndromic hereditary PA for the congenital form
      of a monosymptomatic or isolated PA. This surprisingly high frequency in the
      Caucasian population prompted us to extend our search to other ethnic groups. We
      performed a questionnaire-based screening among 198 native Indian students at
      Banaras Hindu University in Varanasi. In a then selected subset, we found after
      further detailed diagnostic interviews one Bengali female student with visual
      agnosia for face recognition only. Several other members of her large family
      reported the same impairment of face recognition. The segregation pattern of PA
      in this family is also compatible with autosomal-dominant inheritance.

PMID- 17186315
TI  - In situ monitoring by quantitative Raman spectroscopy of alcoholic fermentation
      by Saccharomyces cerevisiae under high pressure.
AB  - We monitored alcoholic fermentation in Saccharomyces cerevisiae as a function of
      high hydrostatic pressure. Ethanol production from 0.15 M glucose was measured by
      Raman spectroscopy in situ in a diamond-anvil cell. At 10 MPa, fermentation
      proceeds three times faster than at ambient pressure and the fermentation yield
      is enhanced by 5% after 24 h. Above 20 MPa, the reaction kinetics slows down with
      increasing pressure. The pressure above which no more ethanol is produced is
      calculated to be 87 +/- 7 MPa. These results indicate that the activity of one or
      several enzymes of the glycolytic pathway is enhanced at low pressure up to 10
      MPa. At higher pressures, they become progressively repressed, and they are
      completely inhibited above 87 MPa. Although fermentation was predicted to stop at
      ca. 50 MPa, due to the loss of activity of phosphofructokinase, the present study
      demonstrates that there is still an activity of ca. 30% of that measured at
      ambient pressure at 65 MPa. This study also validates the use of Raman
      spectroscopy for monitoring the metabolism of living microorganisms.

PMID- 17186318
TI  - Production design and evaluation of a novel breast phantom with various breast
      glandular fractions.
AB  - The purpose of this study was to evaluate the production design of a novel breast
      phantom, which has adjustable breast glandular fractions and potential
      application in the mammography quality assurance/quality control system. The
      breast phantom was based on a urethane resin that was used to adjust the breast
      glandular fraction by varying the amount of plasticizer added. The resin was
      cured at constant temperature and humidity. Theoretical phantom properties, such
      as elemental composition, specific density, effective atomic number, electron
      density, and linear attenuation coefficients, at various energies were compared
      to those of breast tissue tabulated in the ICRU 44. These properties were also
      compared to polymethyl methacrylate resin and BR12. The novel breast phantom was
      made to represent breast glandular content calculated from breast tissue of the
      ICRU 44. We hypothesized that the breast phantom theoretical properties are
      approximately equal to those of the BR12, which is known for being an excellent
      substitute breast phantom. It was found that the phantom can be used to improve
      both mammography performance and dosimetry.

PMID- 17186319
TI  - Psychophysical evaluation of calibration curve for diagnostic LCD monitor.
AB  - PURPOSE: In 1998, Digital Imaging Communications in Medicine (DICOM) proposed a
      calibration tool, the grayscale standard display function (GSDF), to obtain
      output consistency of radiographs. To our knowledge, there have been no previous
      reports of investigating the relation between perceptual linearity and
      detectability on a calibration curve. MATERIALS AND METHODS: To determine a
      suitable calibration curve for diagnostic liquid crystal display (LCD) monitors,
      the GSDF and Commission Internationale de l'Eclairage (CIE) curves were compared
      using psychophysical gradient delta and receiver operating characteristic (ROC)
      analysis for clinical images. RESULTS: We succeeded in expressing visually
      recognized contrast directly using delta instead of the just noticeable
      difference (JND) index of the DICOM standard. As a result, we found that the
      visually recognized contrast at low luminance areas on the LCD monitor calibrated
      by the CIE curve is higher than that calibrated by the GSDF curve. On the ROC
      analysis, there was no significant difference in tumor detectability between GSDF
      and CIE curves for clinical thoracic images. However, the area parameter Az of
      the CIE curve is superior to that of the GSDF curve. The detectability of tumor
      shadows in the thoracic region on clinical images using the CIE curve was
      superior to that using the GSDF curve owing to the high absolute value of delta
      in the low luminance range. CONCLUSION: We conclude that the CIE curve is the
      most suitable tool for calibrating diagnostic LCD monitors, rather than the GSDF
      curve.

PMID- 17186321
TI  - Evaluation of the acute adverse reaction of contrast medium with high and
      moderate iodine concentration in patients undergoing computed tomography.
AB  - PURPOSE: The aim of this prospective study was to evaluate and compare acute
      adverse reactions between contrast medium containing moderate and high
      concentrations of iodine in patients undergoing computed tomography (CT).
      MATERIALS AND METHODS: A total of 945 patients undergoing enhanced CT were
      randomly assigned to receive one of two doses of contrast medium. We then
      prospectively investigated the incidence of adverse reactions. Iopamidol was used
      as the contrast medium, with a high concentration of 370 mg I/ml and a moderate
      concentration of 300 mg I/ml. The frequency of adverse reactions, such as pain at
      the injection site and heat sensation, were determined. RESULTS: Acute adverse
      reactions were observed in 2.4% (11/458) of the moderate-concentration group
      compared to 3.11% (15/482) of the high-concentration group; there was no
      significant difference in incidence between the two groups. Most adverse
      reactions were mild, and there was no significant difference in severity. One
      patient in the high-concentration group was seen to have a moderate adverse
      reaction. No correlation existed between the incidence of adverse reactions and
      patient characteristics such as sex, age, weight, flow amount, and flow rate. The
      incidence of pain was not significantly different between the two groups. In
      contrast, the incidence of heat sensation was significantly higher in the high
      concentration group. CONCLUSIONS: The incidence and severity of acute adverse
      reactions were not significantly different between the two groups, and there were
      no severe adverse reactions in either group.

PMID- 17186320
TI  - Clinicoradiological factors influencing the reversibility of posterior reversible
      encephalopathy syndrome: a multicenter study.
AB  - PURPOSE: The aim of this retrospective study was to clarify the relation between
      the reversibility of posterior reversible encephalopathy syndrome (PRES) with
      three factors: the anatomical region of the brain involved, the background
      clinical cause, and the diffusion weighted image (DWI) intensity of PRES lesions.
      MATERIAL AND METHODS: This multicenter study, conducted by the PRES Study Group
      of the Neuroradiology Workshop, involved 52 cases from 28 institutions. Initial
      and follow-up magnetic resonance imaging were compared regarding the
      reversibility of PRES lesions according to anatomical location and clinical
      background. Initial DWI and apparent diffusion coefficient (ADC) maps were
      reviewed in 20 cases. RESULTS: Reversibility was significantly lower (P < 0.01)
      in the brain stem (44%) and deep white matter (47%) compared to the other
      cortical and subcortical areas (76%-91%). The reversibility was greater in the
      eclampsia subgroup followed by the hypertension and chemotherapy subgroups. DWI,
      even with ADC maps, had limitations in predicting the outcome of PRES lesions.
      CONCLUSION: The typical cortical and subcortical PRES lesions showed
      reversibility, whereas the brain stem and deep white matter lesions showed less
      reversibility. PRES due to eclampsia showed maximum reversibility compared to
      hypertension- and drug-related PRES. DWI, even with ADC maps, had limitations in
      predicting the course of PRES.

PMID- 17186322
TI  - Dosimetric consideration of individual 125I source strength measurement and a
      large-scale comparison of that measured with a nominal value in permanent
      prostate implant brachytherapy.
AB  - PURPOSE: We investigated the difference between measured and manufacturer's
      nominal source strength in a large sample of a single model of (125)I seeds.
      Physical characteristics of single seed measurement by the well-type ionization
      chamber were also investigated to provide dosimetric data. MATERIALS AND METHODS:
      A well-type ionization chamber with a single seed holder was used to measure
      source strength of all 1935 (125)I seeds implanted in the initial 28 patients in
      our hospital. Physical characteristics including linearity of readings for
      different integral time intervals, reproducibility, isotropy, and axial
      positional sensitivity were assessed. To calculate the source strength, the
      integral charge during 30 s was measured and converted to air kerma strength. The
      nominal activity stated by the manufacturer was compared with the measured value.
      RESULTS: Linearity, reproducibility, and isotropy of the well-type ionization
      chamber were within 0.2%. Measured source strength was on average 2.1% (range 
      7.6% to +7.2%), lower than the nominal value. Standard deviation of all measured
      seeds was 2.0%. The maximum difference between the measured and the
      manufacturer's nominal source strength in each patient was -3.7%. The standard
      deviation averaged 1.6%. CONCLUSION: The nominal source strength of the (125)I
      seeds agreed well with the measured value. Our study can be helpful as guidance
      for individual (125)I seed source strength measurement.

PMID- 17186323
TI  - Solitary pulmonary metastases from renal cell carcinoma: comparison of high
      resolution CT with pathological findings.
AB  - PURPOSE: The aim of this study was to examine the radiographic features of
      solitary pulmonary metastases from renal cell carcinoma by comparing high
      resolution CT (HRCT) findings with histopathological observations. MATERIALS AND
      METHODS: Three thoracic radiologists retrospectively reviewed HRCT findings from
      eight patients who underwent surgery on the basis of the diagnosis of solitary
      pulmonary metastatic renal cell carcinoma. The histopathological diagnoses for
      six of these eight lesions were metastases from clear cell carcinoma of the
      kidney, one case was a metastasis from papillary renal cell carcinoma, and the
      remaining case was a metastasis from a poorly differentiated carcinoma including
      predominantly spindle cells, papillary cells, and clear cells. RESULTS: The HRCT
      findings of all cases of clear cell carcinoma showed solid nodular lesions
      without ground-glass attenuation (GGA). The HRCT findings for one case of
      papillary renal cell carcinoma showed a lobulated nodule with a small amount of
      GGA in an area in the periphery and an air bronchogram. The HRCT findings of the
      remaining case of poorly differentiated carcinoma showed an ill-defined nodule
      with a GGA area and pleural indentations. CONCLUSION: In brief, solitary
      pulmonary metastases from renal cell carcinoma may present as a smoothly
      marginated nodule, lobulated nodule, or a nodule with peripheral GGA.

PMID- 17186324
TI  - Aneurysm of a systemic artery supplying the normal basal segments of the left
      lower lobe.
AB  - The case of an aneurysm of a systemic artery supplying otherwise normal basal
      segments of the left lower lobe is presented. The diagnosis was correctly made
      postprocessed with three-dimensional reformatting using a multidetector row CT
      (MDCT) scanner. Conventional angiography was obviated.

PMID- 17186325
TI  - Subpial schwannoma of the cervical spinal cord mimicking an intramedullary tumor.
AB  - We report a rare case of a subpial schwannoma of the cervical cord mimicking an
      intramedullary tumor in a 65-year-old woman. The magnetic resonance imaging
      findings are presented and discussed.

PMID- 17186326
TI  - Gene therapy targeting kidney diseases: routes and vehicles.
AB  - Renal gene therapy may offer new strategies to treat diseases of native and
      transplanted kidneys. Several experimental techniques have been developed and
      employed using nonviral, viral, and cellular vectors. The most efficient viral
      vector for in vivo transfection appears to be adenovirus. In addition, enhanced
      naked plasmid techniques, such as the hemagglutinating virus of Japan (HVJ)
      liposome method, electroporation, the hydrodynamic method, and ultrasound with
      microbubbles, are promising. Trapping genetically modified macrophages in the
      inflamed kidneys is an elegant method for site-specific gene delivery. The choice
      of delivery vehicle as well as the administration route determines the site of
      transduction. In conclusion, for both in vivo and ex vivo renal transfection,
      enhanced naked plasmids, adenoviruses, and modified cell vectors offer the best
      prospects for effective clinical application. Moreover, the development of safer
      and nonimmunogenic vectors may realize clinical renal gene therapy in the near
      future.

PMID- 17186327
TI  - Computer analysis of the significance of the effective osmolality for urea across
      the inner medullary collecting duct in the operation of a single effect for the
      counter-current multiplication system.
AB  - BACKGROUND: Although urea and water are transported across separate pathways in
      the apical membrane of the inner medullary collecting duct (IMCD), the existence
      of a cellular diffusion barrier as an unstirred layer makes it possible to use
      coefficients of effective osmotic force (sigma*) as equivalent to reflection
      coefficients. The difference in effective osmolality between urea and NaCl across
      the IMCD becomes a driving force for water if the compositions of solutes are
      different between tubular lumen and interstitium. Since reported values for
      sigma*(urea) are discrepant, we compared the efficiency of a single effect in the
      counter-current system between an ascending thin limb (ATL) and the IMCD, with
      the interposition of capillary networks (CNW), between two models with
      sigma(urea)* = 0.7 (model 1) and sigma(urea)* = 1.0 (model 2). METHODS: The time
      courses (within 3 s) of solute and the water transport profiles among ATL, CNW,
      and IMCD were simulated with a computer in the absence of flow in each
      compartment. RESULTS: In spite of small differences in the profiles of urea and
      NaCl concentrations between the two models, model 1 displayed a larger volume
      flux in the IMCD than model 2, resulting in an increase of osmolality in the IMCD
      and a decrease of osmolality in the ATL. These findings are vital for the
      operation of the counter-current multiplication system. CONCLUSIONS: The concept
      of coefficients for effective osmotic force can be applied to the counter-current
      model between the IMCD and the ATL with the interposition of CNW. The model of
      sigma(urea)* = 0.7 is more efficient than that of sigma(urea)* = 1.0.

PMID- 17186328
TI  - The suppressive effects of dietary protein restriction on the progression of
      renal impairment in OLETF rats.
AB  - BACKGROUND: The suppressive effect of dietary protein restriction on the
      progression of diabetic nephropathy remains controversial. We investigated the
      effects of protein and energy restrictions on both albuminuria and morphology
      using diabetic-prone Otsuka Long-Evans Tokushima fatty (OLETF) rats. METHODS: In
      this study, male OLETF rats were divided into two groups according to their
      energy intake. They were then further divided into three subgroups based on their
      amount of dietary protein, which ranged between 10% and 30% of their total
      intake. Urinary albumin excretion (UAE) was used as a marker of renal impairment,
      and body weight fasting (F) and postchallenge (P), blood glucose (BG) levels, and
      systolic blood pressure (SBP) were all measured during various experimental
      periods up to 28 weeks of age. RESULTS: The OLETF rats fed with the high-calorie
      diet started to gain weight at 12 weeks, and their FBG and PBG were elevated at
      22 weeks, while SBP did not differ between the two groups. In addition, UAE
      increased significantly in the rats fed with the high-calorie diet. However, the
      increasing rates of UAE with age were higher in the rats with a higher protein
      diet within the same energy groups. UAE correlated well with the amounts of
      dietary energy and protein at 16 and 28 weeks of age, while it correlated with
      both the FBG and PBG at only 28 weeks of age. A linear regression analysis, using
      the data obtained at 28 weeks, showed that the amount of protein intake and FBG
      explained 63.4% and 23.9% of the variation in UAE, respectively. Histological
      studies revealed that protein and energy restriction markedly reduced the
      sclerotic changes of the glomeruli. CONCLUSION: Dietary protein restriction
      starting very early in the life of OLETF rats, in combination with energy
      restriction, clearly suppressed UAE and the typical morphological changes that
      otherwise occurred at around 16 weeks of age. This method also seemed to be more
      effective than energy restriction alone in slowing down any increase in UAE. The
      influence of BG levels on UAE was lower at an early age, while it became an
      increasingly important factor at later ages in the experimental rat model.

PMID- 17186329
TI  - Matrix metalloproteinase-2, matrix metalloproteinase-9, and tissue inhibitor of
      metalloproteinase-1 in the peripheral blood of patients with various glomerular
      diseases and their implication in pathogenetic lesions: study based on an enzyme
      linked assay and immunohistochemical staining.
AB  - BACKGROUND: Various glomerular diseases progress to end-stage renal failure due
      to an accumulation of the mesangial matrix (MM) and a thickening of the
      glomerular basement membrane (GBM). Both the MM and GBM are consistently
      metabolized through the synthesis and destruction of the matrix. Such synthesis
      is influenced by transforming growth factor-beta (TGF-beta) and other factors,
      whereas the destruction is presumed to be mediated by both matrix
      metalloproteinases (MMPs) and inhibitors of matrix metalloproteinases (TIMPs).
      Based on such evidence, we tried to detect MMP-2, MMP-9, and TIMP-1 in the
      peripheral blood of patients with various glomerular diseases. METHODS: Serum was
      used to detect MMP-2 and TIMP-1, while plasma was used to detect MMP-9. These
      enzymes were detected using an enzyme-linked assay. RESULTS: The findings showed
      an increased level of MMP-2 in patients with a alteration of GBM, typically
      membranous nephropathy (MN), regardless of the differences in their etiological
      processes. In contrast, MMP-9 did not show a strong association with any specific
      glomerular abnormalities. However, it mainly tended to increase in patients with
      MM accumulation. In addition, the localization of MMP-2, MMP-9, and TGF-beta1 was
      studied using immunohistochemical staining. MMP-2 was demonstrated to exist in
      the glomerular capillary loop (GCL) as well as in the mesangial cells and the
      mesangial matrix. MMP-9 was found to exist in mesangial cells and the matrix,
      GCL, infiltrated neutrophils, and some tubular epithelial cells. Positive
      staining for TGF-beta1 in GCL was found to be associated with an increased level
      of MMP-2 in patients with MN, whereas in MM such positive staining was not
      necessarily associated with an increased level of MMP-9. CONCLUSIONS: These
      results therefore suggest that MMP-2 plays an important role in the degradation
      of GBM, while MMP-9 only moderately affects the degradation of MM.

PMID- 17186330
TI  - Carbonic-adsorbent AST-120 reduces overload of indoxyl sulfate and the plasma
      level of TGF-beta1 in patients with chronic renal failure.
AB  - BACKGROUND: We previously reported a significant increase in plasma TGF-beta1 in
      patients with chronic renal failure (CRF). Progression of CRF may be caused by
      persistent renal production of TGF-beta1. In CRF rat models, an oral carbonic
      absorbent (AST-120) reduces the expression of the TGF-beta1 gene in the kidney,
      and delays the progression of CRF, in part by alleviating the overload of indoxyl
      sulfate. The aim of this study was to evaluate the effect of AST-120 on plasma
      levels of indoxyl sulfate and TGF-beta1 in CRF patients. METHODS: Ten CRF
      patients (aged 59.3 +/- 9.5 years, 5 men, serum creatinine 4.37 +/- 1.72 mg/dl)
      were enrolled in this study. All patients maintained a regular dietary therapy
      and the same medication throughout the study. AST-120 was added at a dose of 6
      g/day. Parameters including the slope of the reciprocal of the serum creatinine
      time plot, plasma indoxyl sulfate level, and plasma and urinary levels of TGF
      beta1 were compared before and after the treatment with AST-120. The mean
      observation periods before and after the treatment were 9.7 +/- 2.8 and 6.5 +/-
      2.9 months, respectively. RESULTS: Administration of AST-120 significantly
      reduced the plasma levels of indoxyl sulfate (1.42 +/- 1.50 vs. 1.26 +/- 1.40
      mg/dl, P < 0.05) and TGF-beta1 (17.9 +/- 7.2 vs. 10.6 +/- 4.7 ng/ml, P < 0.05)
      and improved the slope of the reciprocal of serum creatinine (-0.061 +/- 0.041
      vs. -0.032 +/- 0.055 dl/mg/year, P < 0.05). CONCLUSIONS: These results support
      the notion that indoxyl sulfate and TGF-beta1 may be involved in the progression
      of CRF, and that the oral adsorbent AST-120 may suppress the progression, at
      least in part, by reducing overproduction of TGF-beta1.

PMID- 17186331
TI  - Meta-analysis of antiplatelet therapy for IgA nephropathy.
AB  - BACKGROUND: Antiplatelet agents have been widely used in the management of
      immunoglobulin A (IgA) nephropathy in the Japanese population. To systematically
      evaluate the effects of antiplatelet agents for IgA nephropathy, we conducted a
      meta-analysis of the published studies. METHODS: Data sources consisted of
      MEDLINE, EMBASE, the Cochrane Library, Ityu-shi (Japanese medical database), and
      bibliographies from the studies. The quality of the studies was evaluated from
      the intention to treat analysis and allocation concealment, as well as by the
      Jadad method. Meta-analyses were performed on the outcomes of proteinuria and
      renal function. RESULTS: Seven articles met the predetermined inclusion criteria.
      The use of antiplatelet agents showed statistically significant effects on
      proteinuria and renal function. The pooled risk ratio for proteinuria was 0.61
      (95% confidence intervals (CI) 0.39-0.94) and for renal function it was 0.74 (95%
      CI 0.63-0.87). CONCLUSIONS: Antiplatelet agents resulted in reduced proteinuria
      and protected renal function in patients with IgA nephropathy. However, studies
      of high-quality design were rare, and most studies assessed surrogate outcomes.
      More properly designed studies are needed to reach a definitive assessment of
      this matter.

PMID- 17186332
TI  - Effect of an educational program on the predialysis period for patients with
      chronic renal failure.
AB  - BACKGROUND: The purpose of the treatment and management of chronic renal failure
      during the predialysis period is mainly to retard the progression of the
      deterioration of renal function. Optimal dialysis initiation is important to
      improve the patient's outcome after therapy. We investigated whether providing
      information through an original educational program could facilitate dialysis
      initiation, with the patient in a better condition, and therefore greater cost
      effectiveness. METHODS: One hundred and seventy-six patients who underwent
      dialysis initiation for chronic renal failure in our hospital between April 2002
      and March 2005 were divided into two groups according to their participation or
      nonparticipation in an educational program. Participation in the education
      program was of their own free will. The instructors consisted of nephrologists,
      nursing staff, clinical engineering technologists, national registered
      dietitians, and medical social workers. We investigated whether the education
      program facilitated trouble-free dialysis initiation by comparing findings of
      blood tests at the start, the existence of heart-failure symptoms, type of blood
      access, percentage of scheduled initiation, and the number of days and cost of
      hospitalization as indices between participating and nonparticipating groups.
      RESULTS: The number of patients using a double-lumen dialysis catheter, and the
      duration and cost of hospitalization in training the participating group, were
      significantly less than those in the nonparticipating group. Although there was
      no significant difference in renal function at the initiation of renal
      replacement therapy (RRT) between the two groups, serum albumin, hemoglobin, and
      hematocrit in the participating group were significantly higher than those of the
      nonparticipating group. CONCLUSIONS: This study suggests that providing
      sufficient information before dialysis initiation may be effective in both
      physical condition at dialysis initiation, and medical economic benefits through
      the understanding of the dialysis.

PMID- 17186333
TI  - A case of recurrent renal failure associated with metabolic alkalosis induced by
      protracted vomiting.
AB  - We describe a case of recurrent deterioration of renal function in a 54-year-old
      man who was found to have metabolic alkalosis, with a maximum PaCO(2) of 73.9
      mmHg and a bicarbonate concentration of 55.3 mmol/l. He had a gradual
      exacerbation of nausea and vomiting due to atrophic gastritis, with a scarred,
      deformed pyloric part of the stomach and a duodenal bulb secondary to chronic
      peptic ulcer. His metabolic alkalosis and deteriorated renal function were
      corrected by intravenous saline with or without potassium chloride. However, his
      recovered creatinine clearance was at most 60 l/day (41.6 ml/min). A renal biopsy
      revealed cellular infiltration of mononuclear cells and atrophic change in the
      tubulointerstitium, suggesting chronic interstitial nephritis. Latent renal
      insufficiency and dehydration induced by protracted vomiting may easily induce a
      rapid and recurrent deterioration of renal function, and control of vomiting
      seemed to be the cardinal measure. Initially, his nausea and vomiting seemed to
      be successfully controlled by medication, however, they later became persistent
      and surgical correction of the stomach was carried out. Postoperative recovery
      was smooth, and the patient's vomiting and recurrent deterioration of renal
      function finally settled.

PMID- 17186334
TI  - Concurrent FSGS and Hodgkin's lymphoma: case report and literature review on the
      link between nephrotic glomerulopathies and hematological malignancies.
AB  - BACKGROUND: The link between the nephrotic syndrome (NS) and malignancy was first
      described in 1922. In solid tumors, the NS is most often due to membranous
      glomerulonephropathy, whereas in common hematological malignancies, minimal
      change disease predominates. Focal segmental glomerulosclerosis (FSGS) is among
      the least frequently reported renal lesion associated with malignancy. METHODS:
      We report a case of the simultaneous diagnoses of FSGS and Hodgkin's lymphoma,
      and review the literature on various nephrotic glomerulonephropathies associated
      with common leukemia and lymphoma. RESULTS: Although nephrotic
      glomerulonephropathies rarely occur in association with acute leukemia, they have
      often been described in chronic lymphocytic leukemia (CLL). Membranoproliferative
      glomerulonephropathy and membranous glomerulonephropathy are the most common
      lesions observed in CLL. Nephrotic glomerulonephropathies have also been well
      documented among patients with lymphomas, in particular, Hodgkin's lymphoma.
      While minimal-change disease is most commonly found in association with Hodgkin's
      lymphoma, more diverse and complex renal lesions are associated with non
      Hodgkin's lymphoma. FSGS remains a rare association with hematological
      malignancies. CONCLUSIONS: Nephrotic glomerulonephropathies are not only linked
      to solid-organ tumors, but also to hematological malignancies. A thorough
      evaluation, including a physical examination for lymphadenopathy and
      organomegaly, as well as a hematological evaluation, must be performed in all
      patients presenting with nephrotic glomerulonephropathies.

PMID- 17186335
TI  - Severe thiamine deficiency resulted in Wernicke's encephalopathy in a chronic
      dialysis patient.
AB  - A 64-year-old male patient with diabetic nephropathy had been treated with
      maintenance hemodialysis therapy for 4 years, and had developed disturbed
      consciousness. The disturbance was firstly noticed by a primary care doctor who
      recognized slow responses in conversation. Prior to developing this symptom, the
      patient had noticed a loss of appetite for about 2 weeks. During a period of
      observation at an outpatient clinic, the symptoms became worse. He was admitted
      to a primary care hospital for 10 days, but his consciousness level deteriorated
      and he became unconscious (JCS 200). About 1 month after the onset of symptoms,
      the patient was transferred to our hospital. A brain computed tomography (CT)
      scan and magnetic resonance imaging (MRI) showed typical abnormal lesions in the
      aquaduct of the midbrain and thalamus, and a diagnosis of Wernicke's
      encephalopathy was made. In addition, the patient's serum thiamine level was
      extremely low (7 ng/ml). He received immediate treatment with intravenous
      thiamine administration (150 mg/day), and this significantly improved his
      symptoms (JCS 2). Dialysis patients may develop water-soluble vitamin deficiency
      as a result of the combination of reduced oral intake and increased loss of
      vitamins into the dialysate. Wernicke's encephalopathy should be considered as
      one of many causes of disturbed consciousness in hemodialysis patients. A rapid
      diagnosis and adequate treatment are essential in order to minimize long-term
      neurological sequelae.

PMID- 17186336
TI  - Interval appendicectomy after appendiceal mass or abscess in adults: what is
      "best practice"?
AB  - There is still much controversy surrounding whether interval appendicectomy is
      appropriate for adults with an appendiceal mass or abscess. The main debate
      centres on the recurrence rate, the complication rate of interval appendicectomy,
      and the potential for underlying malignancy. This review aims to assess current
      practice and to determine whether it is possible to define "best practice" for
      the asymptomatic patient who has had an appendiceal mass or abscess treated
      conservatively. I sent a postal questionnaire to 90 consultant general surgeons
      requesting information about their practice of interval appendicectomy. I also
      conducted a literature search confined to studies involving only adult patients.
      The 77.8% of questionnaires returned revealed that 53% of the surgeons perform
      routine interval appendicectomy, mainly because of concerns about recurrence. The
      preference was for open appendicectomy at 6 weeks to 3 months. The literature
      search revealed a recurrence rate of 10%-25%, with a complication rate of 23%. It
      was evident that the chances of missing malignancy are low and thorough
      investigation is better than interval appendicectomy in detecting colonic cancer.
      The practice of performing interval appendicectomy varies, with just over half of
      the surgeons surveyed performing this procedure routinely. The literature
      provides little evidence that interval appendicectomy is routinely indicated and
      would support the view that it is unnecessary in 75%-90% of cases. However, there
      is scope for further consideration of the use of laparoscopic interval
      appendicectomy and a randomised trial is needed to fully evaluate this issue.

PMID- 17186337
TI  - Fat embolism syndrome.
AB  - Fat embolism syndrome (FES) was first described in 1862, but its frequency today
      is still unclear. A diagnosis of FES is often missed because of a subclinical
      illness or coexisting confusing injuries or disease. Fat embolism syndrome
      develops most commonly after orthopedic injuries, but it has also been reported
      after other forms of trauma such as severe burns, liver injury, closed-chest
      cardiac massage, bone marrow transplantation, and liposuction. Although FES
      usually presents as a multisystem disorder, the most seriously affected organs
      are the lung, brain, cardiovascular system, and skin. Fat embolism syndrome is a
      self-limiting disease and treatment should be mainly supportive. Many drugs have
      been used to treat FES, but the results are inconclusive.

PMID- 17186338
TI  - Transabdominal approach in the surgical management of Morgagni hernia.
AB  - PURPOSE: Morgagni hernias are uncommon diaphragmatic hernias that are generally
      asymptomatic, and so far only limited data have been reported. The objective of
      this retrospective study was to evaluate the outcome of patients presenting with
      a complicated Morgagni hernia and who undergo a transabdominal repair. METHODS:
      Between September 1999 and October 2005, 11 patients with Morgagni hernia were
      operated on in our department. Eight of them had acute presentations because of a
      complicated Morgagni hernia. The patient demographics, presenting symptoms,
      operative approach, and complications were collected. The postoperative course
      was evaluated for morbidity and mortality. RESULTS: The patients' ages ranged
      from 42 to 85 years (mean 69.4). Two (18.2%) patients were male and nine (81.8%)
      patients were female. Chest roentgenograms, computed tomography, and contrast
      meal studies were used as diagnostic utilities. A transabdominal approach was
      used for all patients. One patient died due to pulmonary failure. The mean follow
      up was 2.8 years. There was no recurrence or symptoms regarding the operation in
      the remaining patients. CONCLUSION: We recommend the transabdominal approach in
      patients with Morgagni hernia as it makes it easy to reduce the hernia contents
      and repair of the hernia sac. Moreover, when complicated with strangulation,
      incarceration or perforation, a surgical repair through a transabdominal approach
      is mandatory.

PMID- 17186339
TI  - Is interstitial pneumonia in patients with collagen diseases a contraindication
      to lung cancer surgery?
AB  - PURPOSE: Lung cancer surgery can be dangerous in patients with interstitial
      pneumonia (IP) as acute exacerbation of the IP may prove fatal. It remains
      unclear if patients with collagen diseases (CD), who often suffer from IP, are
      also at increased risk during lung cancer surgery. METHODS: We retrospectively
      examined 17 (3.1%) patients with CD among 545 patients who underwent surgery for
      lung cancer at our institution. RESULTS: Nine patients with rheumatoid arthritis,
      five with systemic sclerosis, two with Sjogren's disease, and one with systemic
      lupus erythematosus were enrolled in this study. Eleven patients (65%) were
      taking corticosteroids at the time of surgery. Fourteen patients underwent
      lobectomy and lymph node dissection, and three patients with pStage IA lung
      cancer underwent pulmonary wedge resection. Pathologically, 11 (65%) patients had
      IP with various inflammatory cellular infiltrations, and three (18%) had
      honeycombing of the lung. Postoperatively, none of the patients suffered acute
      exacerbation of their IP. CONCLUSIONS: Despite the high incidence of IP in
      patients with lung cancer and CD, our results suggest that CD is not a
      contraindication to the surgical resection of lung cancer.

PMID- 17186340
TI  - Surgical treatment of massive splenomegaly and severe hypersplenism secondary to
      extrahepatic portal venous obstruction in children.
AB  - PURPOSE: Massive splenomegaly with severe hypersplenism can occur as a late
      complication of portal hypertension (PH) caused by extrahepatic portal venous
      obstruction (EHPVO) in children. Severe hypersplenism is often refractory to
      treatment with endoscopic sclerotherapy (EST) and shunt surgery. We report our
      experience of managing this disorder surgically. METHODS: We performed
      splenectomy and esophagogastric devascularization via laparotomy in 14 children
      with an average age of 9.7 years. Upper gastrointestinal endoscopy had shown
      esophageal varices of varying grade, and EST had been done for patients with a
      history of bleeding. The indications for surgery were pain and discomfort caused
      by a large spleen greater than 15 cm below the costal margin, and intractable
      symptomatic hypersplenism with a total leukocyte count <2500/mm3 and a platelet
      count <50,000/mm3, or both. RESULTS: Postoperative recovery was uneventful and
      the leukocyte and platelet counts reverted to normal. After follow-up for 1-5
      years, all 14 children were asymptomatic, with improved growth and nutrition and
      no reported episodes of gastrointestinal bleeding, sepsis, or encephalopathy.
      CONCLUSION: Splenectomy with devascularization is effective for children with
      massive splenomegaly and severe hypersplenism secondary to EHPVO.

PMID- 17186341
TI  - Efficacy and limitations of natural killer cell depletion in cyclophosphamide
      induced tolerance.
AB  - PURPOSE: We previously developed a cyclophosphamide (CP)-induced tolerance
      protocol, consisting of an intravenous injection of 1 x 10(8) donor spleen cells
      (SC) given on day 0 and an intraperitoneal injection of 200 mg/kg CP given on day
      2. In the present study, we modified this protocol with natural killer cell (NK)
      depletion in recipient mice, and evaluated the efficacy of tolerance induction.
      METHODS: We used B10.D2 (H-2d; IE+) and B10 (H-2b; IE-) mice as both donors and
      recipients. The recipient mice were treated with donor SC, CP, and donor bone
      marrow cells (BMCs) with or without NK depletion. RESULTS: A higher level of
      mixed chimerism was achieved in the NK-depleted recipients. Survival of both the
      skin and heart donor grafts was significantly prolonged in the NK-depleted
      recipients. Donor reactive Vbeta11+ T cells were found at the same level as in
      untreated control mice. Pretreatment with recipient NK cell depletion was
      effective in inducing higher levels of donor mixed chimerism; however, permanent
      engraftment of donor bone marrow was not achieved. CONCLUSION: Survival of donor
      grafts was remarkably prolonged in the NK cell-depleted group, but
      transplantation tolerance could not be induced. Our results suggest that NK cell
      depletion in CP-induced tolerance conditioning has some effect on the induction
      of donor-specific tolerance.

PMID- 17186342
TI  - Long-term survival of a baby with body stalk anomaly: report of a case.
AB  - Body stalk anomaly is characterized by severe scoliosis, severe pulmonary
      hypoplasia, and giant omphalocele. The prognosis of the disease is poor and most
      obstetricians consider it fatal. Very few patients with body stalk anomaly
      survive. We report the case of a baby diagnosed with body stalk anomaly in fetal
      life, who was saved by intensive care after birth. We closed the giant
      omphalocele successfully by placing karaya gum sheets over it, which created a
      humidified environment and promoted natural skin epithelization over the skin
      defect.

PMID- 17186343
TI  - Needle track dissemination of follicular thyroid carcinoma following fine-needle
      aspiration biopsy: report of a case.
AB  - Few reports have been concerned with the risk of needle track dissemination of
      tumor cells following fine-needle aspiration biopsy, especially for follicular
      thyroid nodules. A 61-year-old woman who underwent fine-needle aspiration biopsy
      and surgery 5 years previously for follicular thyroid adenoma presented with
      nodules that had developed in the sternocleidomastoid and omohyoid muscles of the
      anterior neck. These nodules were located along a line from the skin to the
      thyroid that coincided with the needle track of the previous biopsy. Following
      surgical resection, histological diagnosis determined the nodules to be
      follicular carcinoma. The clinical course and linear arrangement of the lesions
      were highly suggestive of needle track dissemination of tumor cells following
      fine-needle aspiration biopsy. Although fine-needle aspiration biopsy is a useful
      tool for the diagnosis of thyroid nodules, it is important to consider the risk
      of tumor cell dissemination.

PMID- 17186345
TI  - Laparoscopic repair of a gastric volvulus occurring as a long-term complication
      of left pneumonectomy: report of a case.
AB  - Gastric volvulus is an extremely rare late complication of pneumonectomy. We
      report the case of a 61-year-old man who presented with a 1-year history of
      progressive intolerance of solids and weight loss 33 years after a left
      pneumonectomy. Preoperative examinations showed a mesenteroaxial gastric
      volvulus. We performed a laparoscopic Toupet fundoplication and anterior
      gastropexy, following which his symptoms disappeared.

PMID- 17186344
TI  - Primary rhabdomyosarcoma of the breast in a 13-year-old girl: report of a case.
AB  - We report a case of primary alveolar rhabdomyosarcoma of the breast in a 13-year
      old Japanese girl. The patient initially presented with a 13 x 8-cm mass in her
      left breast, which was diagnosed as alveolar rhabdomyosarcoma after an excisional
      biopsy. Genetic expression of the tumor revealed t(2;13)(q35-37;q14). She
      underwent modified radical mastectomy (Bt + Ax) and nine lymph nodes were found
      to be involved. Systemic examinations showed multiple bone and lung metastases 2
      weeks after her operation. Despite chemotherapy with doxorubicin, ifosfamide, and
      actinomycin D, which resulted in remission for 6 months, she died of the disease
      8 months after surgery.

PMID- 17186346
TI  - Nonfamilial juvenile polyposis coli manifesting as massive lower gastrointestinal
      hemorrhage: report of two cases.
AB  - Juvenile polyposis syndrome is an uncommon hamartomatous disorder with
      gastrointestinal (GI) manifestations of varying degree and malignant potential.
      We report the cases of an 8-year-old girl and a 5-year-old girl who suffered
      massive lower GI hemorrhage. Neither patient had a family history of polyposis.
      After the patients were stabilized, radiological evaluation, laparotomy, and
      intraoperative colonoscopy revealed multiple polyps in the colon. Both patients
      underwent total colectomy, mucosal proctectomy, and ileoanal anastomosis. The
      diagnosis of nonfamilial juvenile polyposis was based on the histological
      findings and the absence of a family history. To our knowledge, this presentation
      of juvenile polyposis has been reported only twice before. We discuss the
      clinical features and diagnosis of juvenile polyposis and the treatment options.
      Although juvenile polyposis is a rare condition in children, it should be
      considered in the differential diagnosis of life-threatening GI hemorrhage.

PMID- 17186347
TI  - Intestinal volvulus and perforation caused by multiple magnet ingestion: report
      of a case.
AB  - Ingested magnets can cause intestinal fistulas, perforation, and obstruction.
      There have been reports of magnet ingestion causing intestinal volvulus, but
      multiple magnet ingestion causing perforation and intestinal volvulus in a child
      is very unusual. We report the case of a 4-year-old girl, who ingested four
      magnets she acquired as toys, which caused intestinal volvulus and perforation as
      a result of pressure necrosis, several days after ingestion. At surgery we
      repaired two perforations, but additional bowel resection was not required. The
      patient was discharged on postoperative day 10. If multiple magnet ingestion is
      suspected in a child, the child must be monitored carefully. If there are signs
      of obstruction, emergency surgery is mandatory.

PMID- 17186348
TI  - Long-term survival after repeat resections of metastases in liver, lung, and
      stomach from sigmoid colon cancer: report of a case.
AB  - A 74-year-old female patient underwent a simultaneous colectomy and hepatectomy
      for sigmoid colon cancer and its hepatic metastases. Six months later she
      underwent a hepatectomy for recurrent hepatic metastases; then 10 months later, a
      pulmonary resection for pulmonary metastasis; and 24 months later, a partial
      gastrectomy for gastric metastasis. As of December 2005, at 7 years 6 months
      after the first surgery and at 4 years after the last surgery, the patient is
      still alive with a good quality of life and no sign of recurrence.

PMID- 17186349
TI  - Curative resection performed twice for circular-staple-line recurrence after
      colorectal carcinoma surgery: report of a case.
AB  - Staple-line recurrence is an important pattern of recurrence after colorectal
      carcinoma surgery, occurring in approximately 1% of patients. We report the case
      of a 44-year-old woman who underwent resection of carcinoma recurrence in a
      circular-staple-line twice within 34 months. Initially, she underwent
      sigmoidectomy for carcinoma of the sigmoid colon, followed by end-to-end
      anastomosis, done using a circular stapler. Subsequently, she underwent an
      anterior resection, then a low anterior resection, 12 and 34 months after the
      initial operation, respectively, both to treat a circular-staple-line recurrence
      of the tumor. Histological examination of all resected specimens revealed
      moderately differentiated adenocarcinoma with clear surgical margins and no lymph
      node metastasis. The patient remains well with no evidence of disease 48 months
      after her initial operation. To our knowledge, this is the first reported case of
      curative surgical resection being performed twice for circular-staple-line
      recurrence of colorectal carcinoma. Based on our experience and our review of the
      literature, early detection by follow-up colonoscopy and surgical resection may
      improve the prognosis of patients with a staple-line recurrence after the
      resection of colorectal carcinoma.

PMID- 17186350
TI  - Severe proctitis, perforation, and fatal rectal bleeding secondary to
      cytomegalovirus in an immunocompetent patient: report of a case.
AB  - Cytomegalovirus (CMV) infection is associated with significant morbidity and
      mortality in immunocompromised patients. In immunocompetent individuals, the
      infection is usually subclinical but it can sometimes be life threatening. We
      describe a case of fatal CMV proctitis in a 71-year-old man following an Ivor
      Lewis esophagectomy. After surgery he developed renal failure, methicillin
      resistant Staphylococcus aureus pneumonia, and acute respiratory distress
      syndrome. He recovered but developed melena and massive fresh rectal bleeding.
      Sigmoidoscopy revealed severe proctitis and a biopsy was consistent with
      ischemia. Despite undergoing a proctectomy he continued to bleed and died despite
      every effort. The final histological examination of the rectum revealed a CMV
      infection.

PMID- 17186351
TI  - Left extended hepatectomy for a metastatic gastrointestinal stromal tumor after a
      disease-free interval of 17 years: report of a case.
AB  - Gastrointestinal stromal tumors (GISTs), although rare, are frequently diagnosed
      with liver metastasis. These metastatic GISTs are poorly responsive to
      conventional chemotherapy; however, recent studies report improved survival after
      complete surgical resection of liver metastases. On the other hand, few reports
      describe the treatment of delayed liver metastasis after resection of a primary
      GIST. We report the case of a 55-year-old woman found to have liver metastasis
      from a GIST after a 17-year disease-free interval. The patient underwent a left
      extended hepatectomy for a complete resection of the metastatic GIST and is alive
      and well 30 months later. To our knowledge, this is the longest disease-free
      interval reported in the literature, and emphasizes the importance of considering
      late metastasis when evaluating patients with a history of GIST. Thus, surgical
      resection of delayed liver metastasis from a GIST should be considered as primary
      therapy.

PMID- 17186352
TI  - Ectopic pancreas of the gastric antrum contiguous to a gastrointestinal stromal
      tumor manifesting as upper gastrointestinal bleeding: report of a case.
AB  - A 54-year-old woman was referred to us for investigation of recurrent episodes of
      melena. Gastroduodenal endoscopic examination revealed a hemorrhagic, polypoid
      tumor, about 3 cm in diameter, in the posterior wall of the gastric antrum, near
      the greater curvature. The lesion had a smooth surface with ulceration, and was
      fixed to the sublying planes. The source of the bleeding was the mucosa overlying
      the tumor. We performed a distal subtotal gastrectomy with Roux-en-Y anastomosis.
      Histopathological examination of the resected specimen revealed an ectopic
      pancreas and a gastrointestinal stromal tumor contiguous to the ectopic
      pancreatic tissue in the gastric antrum. The patient was discharged after an
      uneventful postoperative course and has not experienced any recurrence of
      symptoms since.

PMID- 17186353
TI  - Endovascular repair of a traumatic arteriovenous fistula 34 years after the
      injury: report of a case.
AB  - Penetrating extremity injuries can result in the development of arteriovenous
      fistulas (AVFs), whereby normal blood flow through the capillary bed is bypassed.
      Late complications of untreated AVFs include proximal arterial dilatation, venous
      congestion, congestive heart failure, and distal ischemia. We report the case of
      a 57-year-old man who was referred to us for treatment of a traumatic AVF with
      multiple sequelae, 34 years after he sustained a shrapnel injury to his right
      lower leg. We performed successful endovascular repair of this AVF with the
      patient under spinal anesthesia. Computed tomographic angiography (CTA) done 1
      month and 6 months later confirmed AVF exclusion. Patients may present with
      sequelae of traumatic AVFs many years after their initial injury. Endovascular
      repair of AVFs offers several advantages over conventional repair and can be
      performed successfully even in the presence of complex anatomic abnormalities.

PMID- 17186354
TI  - Progression of abdominal aortic aneurysm after endovascular stent-grafting in a
      patient with Behcet's disease: report of a case.
AB  - A 53-year-old man with Behcet's disease was admitted to our hospital for
      investigation of back and lower abdominal pain. Computed tomography (CT) showed a
      projecting saccular aneurysm below the right renal artery. We placed a stent
      graft just below the right renal artery, successfully excluding the abdominal
      aortic aneurysm (AAA). His C-reactive protein level and white blood cell count
      remained elevated after stent-grafting. About 5 months later, he was readmitted
      with recurrent back and lower abdominal pain and CT showed progression of the
      AAA. Thus, we performed straight grafting using a woven Dacron graft just below
      the right renal artery. The patient had an uneventful postoperative course. We
      discuss the controversial issue of treating AAA in patients with Behcet's
      disease, focusing on the indications and timing of surgery.

PMID- 17186355
TI  - An abdominal aortic rupture due to seatbelt blunt injury: report of a case.
AB  - A 66-year-old man, who was a passenger in a car involved in a low-speed head-on
      motor vehicle accident, was rushed to our hospital. His abdomen was tender and
      distended. An enhanced computed tomography scan showed a massive retroperitoneal
      hematoma, and its three-dimensional imaging revealed an active leak of the
      contrast medium from the aortic bifurcation. He went into shock, and was
      immediately transferred to the operating theater. Through a median laparotomy, a
      ruptured site measuring 5 mm in diameter was found at the aortic bifurcation and
      it was closed with sutures under a proximal aortic control. The other organs
      showed no evidence of injury. Because of the remarkable edema of the bowel,
      mesentery, and retroperitoneum, the abdomen was temporarily closed with a mesh
      sheet to prevent the occurrence of abdominal compartment syndrome. A delayed
      closure was then successfully performed 4 days later, and he was discharged with
      no residual sequelae 17 days after the initial operation.

PMID- 17186356
TI  - Occluding the junction of the middle cardiac vein in retrograde cardioplegia: a
      new retrograde cannula for optimizing retrograde cardioplegic delivery.
AB  - Retrograde cardioplegia often fails to provide adequate perfusion of the right
      ventricle and the posterior wall of the left ventricle because of the shunt
      through the thebesian vein. However, much of the retrograde cardioplegic solution
      may leak into the right atrium after veno-venous anastomoses at the apex of the
      heart, especially when a retrograde balloon cannula is inserted too deeply in the
      great cardiac vein, although this is not widely recognized. We designed a new
      retrograde cardioplegic cannula with three self-inflating balloons, which reduced
      the shunt flow by occluding the junction of the middle cardiac vein and improving
      in cardioplegic delivery. We describe the myocardial dye distribution achieved by
      using this new cannula in pig hearts and report the results of its clinical
      application.

PMID- 17186357
TI  - The T393C polymorphism in the gene GNAS1 of G protein is associated with survival
      of patients with invasive breast carcinoma.
AB  - The GNAS1 locus encodes the G(alpha)s protein which stimulates the formation of
      cyclic AMP (cAMP). Subsequently the cAMP pathway mediates various pleiotropic
      effects including regulation of apoptosis and proliferation. We have recently
      shown that genotypes of the single nucleotide polymorphism (SNP) T393C in the
      gene GNAS1 are associated with survival of patients suffering from bladder, renal
      cell and colorectal carcinoma. In the present study, the genotypes of the T393C
      SNP were determined in 279 patients with invasive breast carcinoma. Comparing the
      genotypes with the overall survival as well as important clinico-pathological
      parameters showed that carriers of the T allele had a significantly less
      favourable course of the disease when compared to carriers of the homozygous CC
      genotype. In multivariate analysis the homozygous TT genotype was independently
      associated with a decreased overall survival. Our results suggest that the GNAS1
      T393C SNP is a novel genetic host factor for disease progression in patients with
      invasive breast carcinoma.

PMID- 17186358
TI  - Inhibition of histone deacetylase enhances the anti-proliferative action of
      antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation
      of uterine cells.
AB  - Here we report a novel potential therapeutic strategy using histone deacetylase
      (HDAC) inhibitors to enhance the action of hormonal therapy agents in estrogen
      receptor alpha (ER alpha)-positive breast cancer. HDAC inhibitors [trichostatin A
      (TSA), suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA)], inhibited
      proliferation of MCF-7 breast cancer cells and, in combination with tamoxifen
      inhibited proliferation better than with either agent alone. VPA, an anti
      convulsant drug with HDAC inhibitory activity, enhanced tamoxifen action at doses
      within the concentration range used for anti-convulsive therapy. VPA cooperated
      with tamoxifen in a variety of ER alpha-positive cell lines and was also
      effective when combined with other antiestrogens, and with aromatase inhibition.
      VPA enhanced antiestrogen action by promoting cell death via apoptosis without
      affecting cell cycling. Some of this action may be due to VPA's ability to induce
      the pro-apoptotic gene Bik, which is also induced by antiestrogens. Remarkably,
      VPA blocked the undesirable pro-proliferative action of tamoxifen on uterine
      endometrial cells. Our in vitro results suggest that VPA and other HDAC
      inhibitors have the potential to enhance hormonal therapy for ER alpha-positive
      breast cancer and simultaneously reverse the adverse effects of antiestrogens in
      the uterus.

PMID- 17186359
TI  - Survival after bilateral breast cancer: results from a population-based study.
AB  - BACKGROUND: Controversy exists on the impact of bilaterality of breast cancer on
      survival. We used population-based data to compare survival of women with
      unilateral versus bilateral breast cancer. PATIENTS AND METHODS: At the Geneva
      cancer registry, we identified all 7,912 women diagnosed with invasive breast
      cancer between 1970 and 2002. Breast cancers were categorized as unilateral,
      synchronous bilateral (contralateral tumour diagnosed within six months after the
      first tumour) and metachronous bilateral (contralateral tumour diagnosed over six
      months after the first tumour). With multivariate modelling we compared
      characteristics and survival between women with unilateral and bilateral disease.
      RESULTS: Patients with synchronous bilateral tumours (n = 155, 2.0%) had more
      often lobular histology and less frequently stage I disease than women with
      unilateral disease. Women with metachronous breast cancer (n = 219, 2.8%)
      received less often chemotherapy or hormone therapy for their first tumours. Ten
      year disease-specific survival was similar (66%) after unilateral and
      metachronous bilateral breast cancer, but worse after synchronous bilateral
      cancer (51%). After adjustment, breast cancer mortality risks were not
      significantly increased for women with either synchronous or metachronous
      bilateral disease (Hazard ratios 1.1 (0.8-1.5) and 0.8 (0.5-1.4), respectively).
      CONCLUSION: This large population-based study indicates that bilaterality of
      breast cancer is not associated with impaired survival.

PMID- 17186360
TI  - Breast cancer risk factors and second primary malignancies among women with
      breast cancer.
AB  - PURPOSE: To examine the association between breast cancer risk factors and second
      primary cancers (independent diagnoses occurring at least 12 months after the
      initial breast cancer diagnosis) among breast cancer survivors. METHODS: In this
      population-based study, cancer outcomes among breast cancer survivors first
      diagnosed during 1987-2000 were investigated. Invasive breast cancer cases were
      identified from the statewide tumor registry and interviewed regarding their pre
      diagnosis risk factors, including reproductive and lifestyle characteristics,
      approximately 1 year after diagnosis. Data on second primary cancers (not
      recurrences) and deaths were obtained by linkage with tumor registry reports and
      death certificates through December 31, 2002. Hazard ratios (HR) were estimated
      using proportional hazards regression stratified by age and adjusted for stage
      and other factors. RESULTS: Among the 10,953 breast cancer cases, 10.8%
      experienced a second cancer diagnosis within an average of 7 years (including 488
      breast, 132 colorectal, 113 endometrial, and 36 ovarian cancers). Risk of a
      second primary breast cancer increased according to low parity (P = 0.002), older
      age at menopause (P = 0.08), greater body mass index (P = 0.003) and adult weight
      gain (P = 0.02), and a family history of breast cancer-particularly among women
      with 2 or more first-degree affected relatives (HR = 1.8, 95% CI: 1.1-2.9).
      Reduced risk of colorectal cancer after breast cancer was observed in relation to
      older ages at menarche (P = 0.05), younger age at menopause (P = 0.04),
      postmenopausal hormone use (HR = 0.4, 95% CI: 0.3-0.7), normal body mass index (P
      = 0.07), and infrequent alcohol consumption (P = 0.01). Second endometrial cancer
      risk was associated with increasing body mass index (P < 0.01) and adult weight
      gain (P = 0.03). Risk of second ovarian cancer appeared related to recent alcohol
      intake and family history of breast cancer. Women who reported consuming any
      alcohol appeared to have a 55% reduction in ovarian cancer risk (95% CI: 0.2-1.0)
      compared to non-drinkers, while having 2 or more first-degree relatives with
      breast cancer was associated with an increased risk of ovarian cancer (HR = 4.3,
      95% CI: 1.3-14.6). CONCLUSION: This study suggests that family history of breast
      cancer as well as potentially modifiable characteristics including body weight,
      alcohol intake, and postmenopausal hormone use may be associated with risk of a
      second cancer diagnosis among breast cancer cases.

PMID- 17186361
TI  - Provider's volume and quality of breast cancer detection and treatment.
AB  - For many health conditions, the process or result of medical procedures improves
      with increasing caseload. The evidence about breast cancer has not been
      thoroughly assessed. This review synthesizes the literature about provider's
      volume and performance in either breast cancer screening with mammography or
      treatment. Articles published in English between 1990 and 2006 were identified by
      a computerized search and by review of reference lists. In screening with
      mammography, the reading volume of the radiologist and the screening volume of
      the facility influence different components of performance. The most conclusive
      evidence for breast cancer treatment concerns the association between the
      surgeon's caseload and the process or end-results of therapeutic interventions.
      Although the mechanisms of these associations still need to be clarified, large
      provider's volume in screening mammography or breast cancer treatment is often
      related to the quality of medical interventions.

PMID- 17186362
TI  - Ultra-fast biosensors and multi-photon microscopy in the future of brain studies.
AB  - The direct, highly selective and sensitive real-time imaging of neuro- and
      biochemical mediators is the only way to clarify precisely the chemistry of the
      brain and to discover the key molecular targets involved in regulation of brain
      homeostasis. To realize that, we need: high-speed deep-tissue imaging techniques
      with high spatial and temporal resolution; and ultra-fast and highly selective
      molecular sensors, giving a possibility to monitor target molecules directly in
      their physiological environment; in addition, these molecular sensors have to be
      comparatively small and permeable for blood-brain barrier, to be applicable in
      brain studies. The present view accents on the perspectives for development of
      direct approach for investigation of function/flow coupling phenomenon in the
      brain, based on the current progress in development of ultra-fast molecular
      sensors for direct visualization of biochemical mediators (e.g., nitric oxide, Ca
      ions), and high-speed two-photon/multi-photon deep-tissue imaging.

PMID- 17186363
TI  - Do haplogroups H and U act to increase the penetrance of Alzheimer's disease?
AB  - 1. Alzheimer's disease (AD) is the most common form of dementia in the elderly in
      which interplay between genes and the environment is supposed to be involved.
      Mitochondrial DNA (mtDNA) has the only noncoding regions at the displacement loop
      (D-loop) region that contains two hypervariable segments (HVS-I and HVS-II) with
      high polymorphism. mtDNA has already been fully sequenced and many subsequent
      publications have shown polymorphic sites, haplogroups, and haplotypes.
      Haplogroups could have important implications to understand the association
      between mutability of the mitochondrial genome and the disease.2. To assess the
      relationship between mtDNA haplogroup and AD, we sequenced the mtDNA HVS-I in 30
      AD patients and 100 control subjects. We could find that haplogroups H and U are
      significantly more abundant in AD patients (P = 0.016 for haplogroup H and P =
      0.0003 for haplogroup U), Thus, these two haplogroups might act synergistically
      to increase the penetrance of AD disease.

PMID- 17186364
TI  - Panic disorder in clinically referred children and adolescents.
AB  - The present study examined the frequency and characteristics of panic disorder in
      children and adolescents who had been referred to a pediatric psychopharmacology
      clinic. Of the 280 children and adolescents evaluated in this clinic, 35 were
      diagnosed with panic disorder using a semi-structured clinical interview (K-SADS)
      and other objective measures. Approximately half of the youngsters with panic
      disorder also met criteria for the diagnosis of agoraphobia. There was extensive
      comorbidity between panic disorder and other internalizing and externalizing
      disorders. Parents reported clinically significant levels of child symptomatology
      on the CBCL. Teacher-and child-reported symptomatology on the CBCL was within the
      normal range. At the same time, it was notable that no child had been referred
      specifically for evaluation or treatment of panic disorder or agoraphobia.
      Implications for clinical assessment/identification and treatment are discussed.

PMID- 17186365
TI  - Predicting change in parenting stress across early childhood: child and maternal
      factors.
AB  - This study examined maternal parenting stress in a sample of 430 boys and girls
      including those at risk for externalizing behavior problems. Children and their
      mothers were assessed when the children were ages 2, 4, and 5. Hierarchical
      linear modeling (HLM) was used to examine stability of parenting stress across
      early childhood and to examine child and maternal factors predicting parenting
      stress at age 2 and changes in parenting stress across time. Results indicated
      that single parenthood, maternal psychopathology, child anger proneness, and
      child emotion dysregulation predicted 2-year parenting stress. Child
      externalizing behaviors predicted initial status and changes across time in
      parenting stress. Stability of parenting stress was dependent upon child
      externalizing problems, as well as interactions between child externalizing
      problems and gender, and child externalizing problems and emotion regulation.
      Results are discussed in the context of mechanisms by which parenting stress may
      influence the development of child externalizing behaviors.

PMID- 17186366
TI  - Effects of different attentional cues on responding to joint attention in younger
      siblings of children with autism spectrum disorders.
AB  - We compared responding to joint attention (RJA) in younger siblings of children
      with ASD (SIBS-ASD; n = 46) and younger siblings of children developing typically
      (SIBS-TD; n = 35). Children were tested between 12 and 23 months of age in a
      situation in which an experimenter directed the child's attention to one of 8
      targets. Each child responded to 10 different combinations of verbal and
      nonverbal cues containing varying levels of attention-specifying information.
      SIBS-ASD had significantly lower overall RJA scores than SIBS-TD. Moderately
      redundant cues were most difficult for SIBS-ASD relative to SIBS-TD; adding a
      point to moderately redundant cues improved RJA for SIBS-ASD, bringing them to a
      level of RJA commensurate with SIBS-TD.

PMID- 17186368
TI  - Factor analysis of the aberrant behavior checklist in individuals with autism
      spectrum disorders.
AB  - Exploratory factor analysis (varimax and promax rotations) of the aberrant
      behavior checklist-community version (ABC) in 275 individuals with Autism
      spectrum disorder (ASD) identified four- and five-factor solutions which
      accounted for >70% of the variance. Confirmatory factor analysis (Lisrel 8.7)
      revealed indices of moderate fit for the five-factor solution. Our results
      suggest that the factor structure of the ABC is robust within an ASD sample. Both
      solutions yielded a three items self-injury factor. Stratifying on this factor,
      we identified significant differences between the high- and low-self injury
      groups on ABC subscales. The emergence of a self-injury factor, while not
      suggestive of a new subscale, warrants further exploration as a tool that could
      help dissect relevant neurobiobehavioral groups in ASD.

PMID- 17186369
TI  - Using theatrical presentations as a means of disseminating knowledge of HIV/AIDS
      risk factors to migrant farmworkers: an evaluation of the effectiveness of the
      Informate program.
AB  - Previous research has suggested that Mexican migrant farmworkers are at elevated
      risk for contracting HIV/AIDS and that they are in need of receiving HIV/AIDS
      related education. The present study evaluated the impact of the Informate
      adolescent theater program on HIV/AIDS knowledge and attitudes among farmworker
      audience members of various ages. Audience members from 7 migrant farmworker
      camps completed a self-administered questionnaire before and after they observed
      the Informate performance. Paired-samples t-tests and McNemar tests indicated an
      increase in knowlege in "modes of HIV transmission," "body fluids that can
      transmit HIV," and items assessing HIV/AIDS "myths." In addition, a greater
      percentage of farmworkers at posttest reported that they believed that condoms
      should always be used during sex. The overall findings from this study suggest
      that theater can be an effective medium for increasing HIV/AIDS-related knowledge
      among migrant farmworkers. However, it is suggested that, because some
      farmworkers held false beliefs regarding modes of HIV transmission after viewing
      the theater program, theater used in combination with other prevention activities
      may provide for a more comprehensive educational experience.

PMID- 17186371
TI  - Psammomatoid ossifying fibroma.

PMID- 17186367
TI  - Early social and emotional communication in the infant siblings of children with
      autism spectrum disorders: an examination of the broad phenotype.
AB  - Infants with older siblings with Autism Spectrum Disorders (ASD-sibs) are at risk
      for socioemotional difficulties. ASD-sibs were compared to infants with typically
      developing older siblings (TD-sibs) using the face-to-face/still-face (FFSF) at 6
      months and the Early Social Communication Scale (ESCS) at 8, 10, 12, 15, and/or
      18 months. ASD-sibs smiled for a lower proportion of the FFSF than TD-sibs and
      lacked emotional continuity between episodes. With respect to TD-sibs, ASD-sibs
      engaged in lower rates of initiating joint attention at 15 months, lower rates of
      higher-level behavioral requests at 12 months, and responded to fewer joint
      attention bids at 18 months. The results suggest subtle, inconsistent, but multi
      faceted deficits in emotional expression and referential communication in infants
      at-risk for ASDs.

PMID- 17186370
TI  - Barriers to and strategies for recruiting Korean Americans for community
      partnered health promotion research.
AB  - While increasing numbers of researchers are targeting ethnic minorities in order
      to address their health disparities, the unique health needs of Korean Americans
      are not well known to the mainstream community, and only relatively few
      systematic research studies have been conducted in this "hard-to reach"
      population. The purpose of this paper is to describe the barriers to recruiting
      participants for health promotion research and to identify facilitators in the
      community that can contribute to this effort. We have analyzed data pertaining to
      the 14 studies we have conducted since 1998, which included a total sample of
      about 2,400 Korean Americans. We describe in detail the unique recruitment
      challenges that we have faced in regard to the culture, language,
      sociodemographic characteristics of the participants, such as gender and age, and
      other community level barriers. Multiple strategies at different levels
      (individual and community) to address these issues are discussed.

PMID- 17186372
TI  - Some observations upon biochemical causes of ataxia and a new disease entity
      ubiquinone, CoQ10 deficiency.
AB  - Some hereditary ataxias are treatable and the insight required for this has come
      from an in depth knowledge of the phenotypes and clinical biochemistry of the
      conditions. This has required both fundamental and translational clinical
      research. Prof John Blass was fortunate to begin his career at what we can now
      recognise as a golden era for such studies and he worked upon two important
      conditions; Refsum's disease and Friedreich's ataxia. More recently the
      mitochondrial encephalomyopathies have been described and similar investigative
      work has been undertaken upon them. Ubiquinone, CoQ(10), deficiency is the most
      recently recognised encephalomyopathy and is itself treatable. Though rare, it is
      becoming increasingly recognised and patients are benefiting from the same
      scholarly approach to its investigation as was afforded Refsums' disease and
      Friedreich's ataxia.

PMID- 17186373
TI  - Does Abeta 42 have a function related to blood homeostasis?
AB  - In this review, I discuss the possibility that Abeta42 has a physiologic function
      in blood vessel homeostasis and the consequences that this might have for
      theories concerning the pathogenesis of Alzheimer's disease and for treatment.

PMID- 17186375
TI  - Colorectal cancer screening among low-income African Americans in East Harlem: a
      theoretical approach to understanding barriers and promoters to screening.
AB  - African Americans (AAs) have the highest incidence rates of colorectal cancer
      (CRC) among all races in the US. These disparities may be attributed to lower
      participation in CRC prevention and control activities [e.g., flexible
      sigmoidoscopy (FS), fecal occult blood testing (FOBT)]. This is a current issue
      in East Harlem where less than half the residents in this area participate in CRC
      screening and mortality rates due to CRC are higher than the national average. We
      examined correlates of FS and FOBT screening among AAs based on the
      transtheoretical model (TTM) of behavior change. One hundred and eleven AA men
      and women, 50 years and older (51-92), low-income, and at average risk for CRC
      were recruited at an ambulatory care center in East Harlem. Assessments focused
      on sociodemographic, medical, psychosocial and TTM variables. The first logistic
      regression model showed that higher levels of education (p < 0.05), greater
      knowledge of FS (p < 0.05), and greater endorsements of Thinking Beyond Oneself
      (p < 0.05) were associated with adherence to FS screening guidelines. The second
      model showed that only greater knowledge of FOBT (p < 0.05) and receiving a
      physician's recommendation (p < 0.01) were significant correlates of adherence to
      FOBT screening guidelines. This study supported the application of components of
      the TTM for FS and FOBT screening among low-income AAs receiving care in an urban
      medical center and illustrated the need for interventions targeting both patients
      and their providers.

PMID- 17186374
TI  - Combination of growth factors enhances remyelination in a cuprizone-induced
      demyelination mouse model.
AB  - Loss of oligodendrocytes (OLs) is often associated with demyelination. PDGF-AA,
      bFGF, NT3 and IGF-1 are known to regulate OL proliferation, survival and/or
      differentiation. Following cuprizone-induced demyelination in mice a combination
      of above four growth factors (GF) was intracranially injected to stimulate
      remyelination in vivo. Activation of cell signaling and transcription factors
      involved in cell proliferation, survival and differentiation was observed in
      response to GF. Increased cell proliferation and migration occurred in corpus
      callosum, lateral ventricles, rostral migratory stream and cerebri at 2-5 days
      post injection (dpi) of GF cocktail. The fate of these newly formed nestin or
      bromodeoxyuridine (BrdU) positive progenitors was traced to proteoglycan NG2 and
      glutathione transferase (GST) pi positive cells, early and mature OL lineage
      markers, respectively. Immunostaining for myelin showed the presence of more
      myelinated fibers in GF-injected brains at 21 dpi. Remyelination in response to
      GF was confirmed by electron microscopy. In conclusion, this combination of GF is
      a promising tool to consider for remyelination strategies.

PMID- 17186376
TI  - How we learnt about iron acquisition in Pseudomonas aeruginosa: a series of very
      fortunate events.
AB  - The ferric uptake repressor (Fur) of Pseudomonas aeruginosa, and a wide
      assortment of other prokaryotic organisms, has been mostly regarded as a negative
      regulator (repressor) of genes involved in iron acquisition (e.g., expression and
      utilization of siderophores) or of iron-regulated genes involved in virulence
      (e.g., toxins). However, there is an emerging picture of an even broader role for
      this protein in basic bacterial biology. Evidence has now accumulated indicating
      that Fur acts in a positive manner as well, and that it has a considerably wider
      impact on gene expression than originally perceived. We discovered that in P.
      aeruginosa Fur directly (i.e., negatively) regulates the expression of two,
      nearly identical tandem small (<200nt) RNA transcripts (sRNA). Our initial
      experiments showed that these Fur-regulated sRNAs (PrrF) affected expression of
      certain genes we initially thought might be directly, but positively, regulated
      by Fur. However, with discovery of the Fur-regulated sRNAs, first in Escherichia
      coli and then in P. aeruginosa, it became clear that Fur, in at least some cases,
      exerts its positive regulatory effect on gene expression by repressing the
      expression a negative regulatory factor (i.e., PrrF), which acts at the
      posttranscriptional level. While a clear picture was already available regarding
      the function of genes (see above) that are directly repressed by Fur (negative
      regulation), the functional classes of genes that are influenced by Fur-repressed
      sRNAs (positive regulation) had not been identified for P. aeruginosa.
      Accordingly we established a set of rigorous criteria, based on microarray
      experimental data, to identify the cohort of genes that are likely to be directly
      influenced by Fur-regulated PrrFs. More than 60 genes that fulfilled these strict
      criteria were identified. These include genes encoding proteins required for the
      sequestration of iron (e.g., bacterioferritins) and genes encoding enzymes
      (superoxide dismutase) vital to defense against iron catalyzed oxidative stress.
      More notably however, we identified more than 30 genes encoding proteins involved
      in carbon catabolism and aerobic or anaerobic respiration that are regulated by
      PrrFs. A significant number of genes encoding enzymes (e.g., aconitase, citrate
      synthase) involved in the TCA cycle are controlled by the PrrFs however, in quite
      a few instances there are genes encoding proteins with redundant functions (i.e.,
      aconitase, citrate synthase) that do not appear to be influenced in any way by
      PrrFs. Based on our microarray experiments, as well as on phenotypic data, we
      propose that the Fur regulated sRNAs (i.e., PrrFs) exert a powerful regulatory
      influence that permits the sparing of vital metabolic compounds (e.g., citrate)
      during periods of iron limitation. These and other data to be presented indicate
      that Fur controlled gene expression in bacteria like P. aeruginosa is
      considerably more imperative and intricate than previously appreciated.

PMID- 17186377
TI  - Molecular mechanism of ferricsiderophore passage through the outer membrane
      receptor proteins of Escherichia coli.
AB  - Iron is an essential nutrient for all microorganisms with a few exceptions.
      Microorganisms use a variety of systems to acquire iron from the surrounding
      environment. One such system includes production of an organic molecule known as
      a siderophore by many bacteria and fungi. Siderophores have the capacity to
      specifically chelate ferric ions. The ferricsiderophore complex is then
      transported into the cell via a specific receptor protein located in the outer
      membrane. This is an energy dependent process and is the subject of investigation
      in many research laboratories. The crystal structures of three outer membrane
      ferricsiderophore receptor proteins FepA, FhuA and FecA from Escherichia coli and
      two FpvA and FptA from Pseudomonas aeruginosa have recently been solved. Four of
      them, FhuA, FecA, FpvA and FptA have been solved in ligand-bound forms, which
      gave insight into the residues involved in ligand binding. The structures are
      similar and show the presence of similar domains; for example, all of them
      consist of a 22 strand-beta-barrel formed by approximately 600 C-terminal
      residues while approximately 150 N-terminal residues fold inside the barrel to
      form a plug domain. The plug domain obstructs the passage through the barrel;
      therefore our research focuses on the mechanism through which the
      ferricsiderophore complex is transported across the receptor into the periplasm.
      There are two possibilities, one in which the plug domain is expelled into the
      periplasm making way for the ferricsiderophore complex and the second in which
      the plug domain undergoes structural rearrangement to form a channel through
      which the complex slides into the periplasm. Multiple alignment studies involving
      protein sequences of a large number of outer membrane receptor proteins that
      transport ferricsiderophores have identified several conserved residues. All of
      the conserved residues are located within the plug and barrel domain below the
      ligand binding site. We have substituted a number of these residues in FepA and
      FhuA with either alanine or glutamine resulting in substantial changes in the
      chemical properties of the residues. This was done to study the effect of the
      substitutions on the transport of ferricsiderophores. Another strategy used was
      to create a disulfide bond between the residues located on two adjacent beta
      strands of the plug domain or between the residues of the plug domain and the
      beta-barrel in FhuA by substituting appropriate residues with cysteine. We have
      looked for the variants where the transport is affected without altering the
      binding. The data suggest a distinct role of these residues in the mechanism of
      transport. Our data also indicate that these transporters share a common
      mechanism of transport and that the plug remains within the barrel and possibly
      undergoes rearrangement to form a channel to transport the ferricsiderophore from
      the binding site to the periplasm.

PMID- 17186378
TI  - Estrogen-dependent growth and estrogen receptor (ER)-alpha concentration in T47D
      breast cancer cells are inhibited by VACM-1, a cul 5 gene.
AB  - Vasopressin-activated calcium mobilizing receptor (VACM-1)/cullin 5 (cul 5)
      inhibits growth when expressed in T47D breast cancer cells by a mechanism that
      involves a decrease in MAPK phosphorylation and a decrease in the early growth
      response element (egr-1) concentration in the nucleus. Since both MAPK and egr-1
      pathways can be regulated by 17beta-estradiol, we next examined the effects of
      VACM-1 cDNA expression on estrogen-dependent growth in T47D cells and on estrogen
      receptor (ER) concentrations. Our results demonstrate that in T47D cells, both
      basal and 17beta-estradiol-dependent increase in cell growth and MAPK
      phosphorylation were inhibited in cells transfected with VACM-1 cDNA. Further,
      Western blot and immunocytochemistry data analyses indicate that ER
      concentrations and its nuclear localization are significantly lower in cells
      transfected with VACM-1 cDNA when compared to controls. These data indicate that
      in the T47D cancer cell line VACM-1 inhibits growth by attenuating estrogen
      dependent signaling responses. These findings may have implications in the
      development of cancer treatments.

PMID- 17186379
TI  - A highly polar xanthophyll of 9'-cis-neoxanthin induces apoptosis in HCT116 human
      colon cancer cells through mitochondrial dysfunction.
AB  - Highly polar xanthophylls of 9'-cis-neoxanthin (neoxanthin) and fucoxanthin,
      which have the characteristic structure of an epoxy group and an allenic bond,
      were previously found to induce apoptosis in human prostate cancer cells. In the
      present study, we found apoptosis induction by neoxanthin in HCT116 human colon
      cancer cells and examined the induction mechanism. The cells exposed to 20 microM
      neoxanthin clearly showed chromatin condensation, DNA fragmentation, and an
      increase in hypodiploid cells. Neoxanthin treatment increased the activities of
      caspase-3, -8 and -9, and the protein levels of their active subunits, except in
      the case of caspase-8. The treatment also caused the loss of mitochondrial
      transmembrane potential at an early stage and subsequently the release of
      cytochrome c and apoptosis-inducing factor (AIF) from mitochondria to cytosol.
      The exposure of neoxanthin directly to mitochondria isolated from the cells
      enhanced the release of cytochrome c and AIF in a dose-dependent manner.
      Approximately 50% of the neoxanthin taken up into the HCT116 cells accumulated in
      the mitochondrial fraction. These results suggest that the accumulation of
      neoxanthin in mitochondria causes the loss of mitochondrial transmembrane
      potential and thereafter releases cytochrome c and AIF, leading to the execution
      of apoptosis.

PMID- 17186380
TI  - Identification of transcriptionally regulated genes in response to cellular iron
      availability in rat hippocampus.
AB  - The present study was attempted to identify transcriptionally regulated genes of
      the normal neurocytes responsive to iron availability. Postnatal rat hippocampus
      cells were primarily cultured either under the iron-loaded or depleted
      conditions. These cultured cells were applied for the generation of subtracted
      complementary DNA libraries by the suppression subtraction hybridization (SSH)
      and for the subsequent identification of differentially expressed transcripts by
      reverse Northern blot. The differentially expressed genes were chosen to perform
      sequencing, and then some of them were performed by Northern blot analysis for
      observation of their expression in the hippocampus of rats with the different
      iron status. The results indicated that five unique transcripts were strong
      candidates for differential expression in cellular iron repletion, one of them is
      a novel sequence (GenBank No. AF 433878), while 26 unique transcripts were strong
      candidates for differential expression in cellular iron deprivation, one of them
      is a novel sequence (GenBank No. AY 912101). The revealed known genes responsive
      to iron availability were previously unknown to respond to iron availability, or
      have not been determined in the brain, have not even been currently determined in
      their physiological and biological functions. Interestingly, the proteins encoded
      by most of the known genes are either directly pointed to or indirectly
      associated with the molecules that play important, even key roles in cellular
      signal transduction and the cell cycle. These findings lead to the important
      suggestion that the cellular responses to iron availability involve extensive
      transcriptional regulation and cellular signal transduction. Therefore, iron may
      serve as a signal, which directly and/or indirectly regulates or modulates cell
      functions.

PMID- 17186381
TI  - Uncovering sociocultural factors influencing the pathway to care of Chinese
      caregivers with relatives suffering from early psychosis in Hong Kong.
AB  - I used a qualitative approach to explore the sociocultural factors influencing
      the pattern of the help-seeking pathway of Chinese caregivers with relatives
      suffering from early psychosis in Hong Kong. Analyses of the interview scripts of
      58 caregivers revealed that they required an average of 5 months and 2.14 helpers
      before their ill relatives could receive formal psychiatric services. Drawing on
      Lin and Lin's model of the Chinese help-seeking pathway as a basis for
      discussion, this study finds that family caregivers engaged in intrafamilial
      coping and expanded in concentric circles to include relatives and friends as
      helpers in the help-seeking pathway. Contrary to Lin and Lin's view that informal
      network members might cause a delay in the help-seeking process, it is revealed
      that informal network members who possessed adequate knowledge of mental illness
      were able to encourage family caregivers to seek help from formal psychiatric
      services. The duration leading to extrafamilial coping was shorter than the one
      implied in Lin and Lin's model. Family caregivers were quite ready to seek help
      from professionals in the formal psychiatric services despite the fact that the
      ill relatives were reluctant to seek treatment due to psychiatric stigma.
      Finally, the findings of this study do not support the existence of the
      "rejection phase" of the help-seeking process proposed by Lin and Lin.

PMID- 17186382
TI  - Global gene expression changes underlying Stachybotrys chartarum toxin-induced
      apoptosis in murine alveolar macrophages: evidence of multiple signal
      transduction pathways.
AB  - The overall mechanism(s) underlying macrophage apoptosis caused by the toxins of
      the indoor mold Stachybotrys chartarum (SC) are not yet understood. In this
      direction, we report a microarray-based global gene expression profiling on the
      murine alveolar macrophage cell line (MH-S) treated with SC toxins for short (2
      h) and long (24 h) periods, coinciding with the pre-apoptotic (<3 h) and
      progressed apoptotic stages of the treated cells, respectively. Microarray
      results on differential expression were validated by real-time RT-PCR analysis
      using representative gene targets. The toxin-regulated genes corresponded to
      multiple cellular processes, including cell growth, proliferation and death,
      inflammatory/immune response, genotoxic stress and oxidative stress, and to the
      underlying multiple signal transduction pathways involving MAPK-, NF-kB-, TNF-,
      and p53-mediated signaling. Transcription factor NF-kB showed dynamic temporal
      changes, characterized by an initial activation and a subsequent inhibition. Up
      regulation of a battery of DNA damage-responsive and DNA repair genes in the
      early stage of the treatment suggested a possible role of genotoxic stress in the
      initiation of apoptosis. Simultaneous expression changes in both pro-survival
      genes and pro-apoptotic genes indicated the role of a critical balance between
      the two processes in SC toxin-induced apoptosis. Taken together, the results
      imply that multiple signaling pathways underlie the SC toxin-induced apoptosis in
      alveolar macrophages.

PMID- 17186383
TI  - Bone marrow cells in the 'pre-metastatic niche': within bone and beyond.
AB  - Metastasis, the spread of invasive carcinoma to sites distant from the primary
      tumor, is responsible for the majority of cancer-related deaths (Weigelt, B.,
      Peterse, J. L., & van 't Veer, L. J. (2005). Breast cancer metastasis: Markers
      and models. Nature Reviews. Cancer, 5, 591-602). Despite progress in other areas
      of cancer therapeutics, the complexities of this process remain poorly
      understood. Consequently, there are few successful treatments that directly
      target this stage of carcinogenesis. Particularly enigmatic is the tissue
      specificity of different tumor types observed in metastatic spread. One example
      is the predilection of colon cancer to spread to liver whereas breast, prostate,
      and lung carcinomas have a particular affinity to target and proliferate in bone.
      In 1889, Stephen Paget observed that circulating tumour cells would only "seed"
      where there was "congenial soil". Since then, attention has focused on explaining
      the dynamic adhesive and migratory capabilities intrinsic to tumor cells.
      Meanwhile, the earliest changes occurring within distant tissues that prime the
      "soil" to receive incoming cancer cells have largely been neglected. Recent work
      characterizing the importance of bone marrow-derived hematopoietic progenitor
      cells (HPC) in initiating these early changes has opened new avenues for cancer
      research and chemotherapeutic targeting (Kaplan, R. N., Riba, R. D., Zacharoulis,
      S., Bramley, A. H., Vincent, L., Costa, C., et al. (2005). VEGFR1-positive
      haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature,
      438, 820-827). This review discusses the inextricable relationship between bone
      stromal components, metastasizing cells, and bone marrow-derived hematopoietic
      cells, and their roles in carcinogenesis and metastasis. Understanding these
      dynamics may help explain the tissue-specific tropism seen in metastasis.
      Moreover, exploring the earliest events promoting circulating cancer cells to
      engraft and establish at secondary sites may expose new targets for diagnostic
      and therapeutic strategies and reduce the morbidity and mortality from metastatic
      disease.

PMID- 17186384
TI  - Perceptual bias in speech error data collection: insights from Spanish speech
      errors.
AB  - This paper studies the reliability and validity of naturalistic speech errors as
      a tool for language production research. Possible biases when collecting
      naturalistic speech errors are identified and specific predictions derived. These
      patterns are then contrasted with published reports from Germanic languages
      (English, German and Dutch) and one Romance language (Spanish). Unlike findings
      in the Germanic languages, Spanish speech errors show many patterns which run
      contrary to those expected from bias: (1) more phonological errors occur between
      words than within word; (2) word-initial consonants are less likely to
      participate in errors than word-medial consonants, (3) errors are equally likely
      in stressed and in unstressed syllables, (4) perseverations are more frequent
      than anticipations, and (5) there is no trace of a lexical bias. We present a new
      corpus of Spanish speech errors collected by many theoretically naive observers
      (whereas the only corpus available so far was collected by two highly trained
      theoretically informed observers), give a general overview of it, and use it to
      replicate previous reports. In spite of the different susceptibility of these
      methods to bias, results were remarkably similar in both corpora and again
      contrary to predictions from bias. As a result, collecting speech errors "in the
      wild" seems to be free of bias to a reasonable extent even when using a multiple
      collector method. The observed contrasting patterns between Spanish and Germanic
      languages arise as true cross-linguistic differences.

PMID- 17186385
TI  - The processing of non-canonically ordered constituents in long distance
      dependencies by pre-school children: a real-time investigation.
AB  - Four experiments were performed which had the goal of determining how and when
      young children acquire the ability to understand long distance dependencies.
      These studies examined the operations underlying the auditory processing of non
      canonically ordered constituents in object-relative sentences. Children 4-6 years
      of age and an adult population participated in the study, which employed a cross
      modal picture priming methodology to determine when constituents in a non
      canonical position are reactivated during ongoing sentence comprehension. The
      results support the view that even very young children have the same structural
      processing reflex seen in adults. Namely, children re-activate a non-canonically
      positioned (fronted) direct object NP immediately at the post-verb gap site
      during sentence processing.

PMID- 17186386
TI  - Statistical inference and forensic evidence: evaluating a bullet lead match.
AB  - This experiment tested the ability of undergraduate mock jurors (N=295) to draw
      appropriate conclusions from statistical data on the diagnostic value of forensic
      evidence. Jurors read a summary of a homicide trial in which the key evidence was
      a bullet lead "match" that was either highly diagnostic, non-diagnostic, or of
      unknown diagnostic value. There was also a control condition in which the
      forensic "match" was not presented. The results indicate that jurors as a group
      used the statistics appropriately to distinguish diagnostic from non-diagnostic
      forensic evidence, giving considerable weight to the former and little or no
      weight to the latter. However, this effect was attributable to responses of a
      subset of jurors who expressed confidence in their ability to use statistical
      data. Jurors who lacked confidence in their statistical ability failed to
      distinguish highly diagnostic from non-diagnostic forensic evidence; they gave no
      weight to the forensic evidence regardless of its diagnostic value. Confident
      jurors also gave more weight to evidence of unknown diagnostic value. Theoretical
      and legal implications are discussed.

PMID- 17186387
TI  - Monogenic diabetes in children and young adults: Challenges for researcher,
      clinician and patient.
AB  - Monogenic diabetes results from one or more mutations in a single gene which
      might hence be rare but has great impact leading to diabetes at a very young age.
      It has resulted in great challenges for researchers elucidating the aetiology of
      diabetes and related features in other organ systems, for clinicians specifying a
      diagnosis that leads to improved genetic counselling, predicting of clinical
      course and changes in treatment, and for patients to altered treatment that has
      lead to coming off insulin and injections with no alternative (Glucokinase
      mutations), insulin injections being replaced by tablets (e.g. low dose in
      HNFalpha or high dose in potassium channel defects -Kir6.2 and SUR1) or with
      tablets in addition to insulin (e.g. metformin in insulin resistant syndromes).
      Genetic testing requires guidance to test for what gene especially given limited
      resources. Monogenic diabetes should be considered in any diabetic patient who
      has features inconsistent with their current diagnosis (unspecified neonatal
      diabetes, type 1 or type 2 diabetes) and clinical features of a specific subtype
      of monogenic diabetes (neonatal diabetes, familial diabetes, mild hyperglycaemia,
      syndromes). Guidance is given by clinical and physiological features in patient
      and family and the likelihood of the proposed mutation altering clinical care. In
      this article, I aimed to provide insight in the genes and mutations involved in
      insulin synthesis, secretion, and resistance, and to provide guidance for genetic
      testing by showing the clinical and physiological features and tests for each
      specified diagnosis as well as the opportunities for treatment.

PMID- 17186388
TI  - Guidelines for the diagnosis of osteoporosis: T-scores vs fractures.
AB  - The development of bone mineral densitimometry methodologies, especially central
      dual energy X-ray absorptiometry (DXA) methods have allowed this quantitative
      tool to be used to diagnose osteoporosis before the first fragility fracture has
      occurred. The World Health Organization osteoporosis working group set the stage
      for the BMD cut-off criteria development. The wide application of DXA has brought
      the treatment of osteoporosis to the primary care level, a very necessary step if
      this increasingly prevalent disease is to have a decline in its incidence. The
      most difficult osteoporosis cases, for which there are many and their associated
      difficult DXA results and interpretation will always require specialists'
      involvement. In particular, the embracement of the WHO absolute fracture risk
      validated project will take DXA to a much greater level of value in making
      management decisions. In particular, the WHO absolute risk data will allow
      physicians, health-economic policy makers, and payors of medical services to come
      closer together to decide which patients are at a level of unacceptable fracture
      risk that justifies treatment intervention. The implementation of this validated
      project will also remove the unacceptable subjective computer printouts on DXA
      reports that often lead to the over-treatment of low risk patients and at times
      the under-treatment of high risk patients. The evolution of the clinical
      interpretation of bone densitometry has been a work in progress. Challenges in
      the clinical measurement of bone strength remain and will also evolve. The field
      of osteoporosis has grown with the use of DXA and will continue to embrace this
      technology as other technologies to measure fracture risk become applied in
      clinical practice.

PMID- 17186389
TI  - Effect of rebamipide on the colonic barrier in interleukin-10-deficient mice.
AB  - Our aim was to study the effect of a mucosal protective agent, rebamipide, on the
      colonic barrier and the immune response in colitis-prone interleukin-10-deficient
      (IL-10-/-) C57BL/6 mice infected with Helicobacter hepaticus. After sacrifice, in
      all mice, control, or previously infected with H. hepaticus, or previously
      infected and treated with rebamipide enema, a histological examination of colonic
      samples was performed, intestinal permeability was studied in Ussing chamber, and
      mesenteric lymph node proliferation and cytokine secretion were measured. Mice
      treated with rebamipide presented a reinforcement of the distal colonic
      epithelial barrier, an increase of mesenteric lymph node cells proliferation, and
      of IFNgamma and IL-12 secretion. These results indicate that in IL-10-/- mice
      with mild colitis, rectally administered rebamipide reinforces the distal colonic
      barrier and has a slight Th1 immuno-stimulatory effect on mesenteric lymph node
      cells. These properties could be helpful in the management of some inflammatory
      bowel diseases.

PMID- 17186390
TI  - A review of aspirin resistance; definition, possible mechanisms, detection with
      platelet function tests, and its clinical outcomes.
AB  - Aspirin (acetylsalicylic acid) is one of the main therapeutics in prevention of
      thrombo-embolic vascular events. Its efficiency is proved in the prevention of
      cardiovascular events. However, antiplatelet effect of aspirin is not absolute in
      all patients and some patients experience thrombo-embolic events despite aspirin.
      These patients are clinically called as aspirin resistant or aspirin non
      responders. Globally, a lot of people are affected by aspirin resistance
      according to the high prevalence of athero-thrombotic vascular diseases. A
      prevalence of 5.5-45% in patients with various cardiovascular disease by
      different laboratory methods has been reported for aspirin resistance. Clinical
      outcome of aspirin resistance has been demonstrated in patients with different
      vascular diseases. Detection of platelet function in patients treated with
      aspirin may be necessary in the prediction of clinical outcome. Point of care
      methods, which have correlated results with the standard light transmittance
      aggregometry may be appropriate choices in the detection of platelets' response
      to antiplatelet therapy. Adequate additional therapies may reduce
      atherothrombotic risks and major cardiovascular events rate in aspirin resistant
      subjects. None of the current researches advised the cessation of aspirin
      therapy. There is need to investigate the efficacy of additional adenosine
      diphosphate receptor antagonists or newer antiplatelet agents in aspirin
      resistant subjects. The intent of this paper is to review the literature
      discussing possible mechanisms, determination techniques, and clinical effects of
      aspirin resistance.

PMID- 17186391
TI  - Unusual thrombotic cardiac complications of Pemphigus vulgaris: a new link?
AB  - We are reporting a case of Pemphigus vulgaris with extensive thrombosis of deep
      veins, pulmonary veins, and cardiac chambers complicated by myocardial
      infarction. The extensive skin lesions prohibited the administration of
      thrombolytics and coronary intervention. The patient was treated conservatively
      with heparin, and oral anticoagulation in addition to steroids and cyclosporine
      with significant resolution of thrombosis.

PMID- 17186392
TI  - Long-term trends in the use of coronary reperfusion strategies in acute
      myocardial infarction: a community-wide perspective.
AB  - BACKGROUND: The objectives of our study were to examine long-term (1986-2003)
      trends in the use of percutaneous coronary interventions (PCI) and thrombolytic
      therapy in the management of patients hospitalized with acute myocardial
      infarction (AMI) while our secondary study goal was to examine factors associated
      with use of these coronary reperfusion strategies. While there have been
      considerable changes in the management of patients hospitalized with AMI over
      time, limited contemporary data are available about changing trends in the use of
      different coronary reperfusion strategies, particularly from the more
      generalizable perspective of a population-based investigation. METHODS: The study
      sample consisted of 9,422 greater Worcester (MA) residents hospitalized with
      confirmed AMI at all metropolitan Worcester medical centers in 10 annual periods
      between 1986 and 2003. RESULTS: Divergent trends in the use of PCI and
      thrombolytic therapy during hospitalization for AMI were noted. Use of
      thrombolytic therapy increased after its introduction to clinical practice in the
      mid-1980's through the early 1990's with a progressive decline in use thereafter.
      In 2003, 3.5% of patients hospitalized with AMI were treated with clot lysing
      therapy. On the other hand, marked increases in the use of PCI during
      hospitalization for AMI were noted over time. In 2003, 42.1% of patients with AMI
      received a PCI. Several demographic and clinical factors were associated with the
      use of these different treatment strategies. CONCLUSIONS: The results of our
      study in a large Northeast community suggest evolving changes in the hospital
      management of patients with AMI. Current management practices emphasize the
      utilization of PCI to restore coronary reperfusion to the infarct related artery.

PMID- 17186393
TI  - Paper-based dosing algorithms for maintenance of warfarin anticoagulation.
AB  - We examined the quality of anticoagulation produced by two paper-based warfarin
      dosing algorithms in a randomized clinical trial of warfarin therapy. Fifty-eight
      patients were randomized to receive warfarin at a target international normalized
      ratio (INR) range of 2.1-3.0 and were followed for an average of 2.7 years. As a
      proportion of total patient-time, the percentage of time spent above, within, and
      below the therapeutic range was 11%, 71%, and 19% respectively. Fifty-six
      patients were randomized to receive warfarin at a higher target INR range (3.1
      4.0) and had INRs within the therapeutic range for 40% of total patient time. We
      conclude that the performance, minimal cost, and ease-of-use of these algorithms
      make them well-suited for patient management within primary-care and research
      settings.

PMID- 17186394
TI  - Delay in invasive risk stratification of women with acute coronary syndrome is
      associated with worse outcomes.
AB  - BACKGROUND: Invasive risk stratification in patients with acute coronary
      syndromes (ACS) has been shown to improve outcomes. There is paucity of data on
      women undergoing invasive risk stratification. We investigated whether the time
      to coronary angiography affects survival of female patients admitted with ACS.
      METHOD: Female patients admitted to the coronary intensive care unit with ACS
      between 1/1/97 and 12/31/00 and undergoing coronary angiography during same
      hospitalization were divided into three groups based on the time to angiography:
      same day, 1-2 days and >2 days. The baseline clinical features, angiography
      results and outcomes were compared between the angiography groups. RESULTS: Of
      the total 350 female patients who fulfilled the inclusion criteria, 63% underwent
      angiography within two days of presentation. Three year mortality rates in women
      undergoing angiography on the same day, 1-2 days and >2-days were 7%, 7% and 22%
      respectively (p = 0.001). Using multivariate analysis, angiography beyond 2 days
      was a significant predictor of mortality among women (OR 2.6, 95% CI 1.3-5.0, p =
      0.006) after adjusting for confounding variables. CONCLUSION: Later invasive risk
      stratification after 2 days of presentation in women with ACS is associated with
      worse survivial. Gender should not be a reason to defer early coronary
      angiography in these patients.

PMID- 17186395
TI  - Misuse of antithrombotic therapy in atrial fibrillation patients: frequent,
      pervasive and persistent.
AB  - PURPOSE: To assess the use of antithrombotic therapy among atrial fibrillation
      (AF) patients in a Brazilian University Heart Hospital (InCor). METHODS AND
      RESULTS: In a cross-sectional study we analyzed the charts of all patients
      treated at InCor in five separate days of 2002 (Phase 1). To assess the impact of
      admission to a cardiology hospital, a follow-up of the AF patients selected in
      Phase 1 was carried out after 1 year (Phase 2). The prevalence of AF in the 3,764
      assessed charts was 8.0% (301 patients). In Phase 1, antiplatelets were
      prescribed to 21.2% and anticoagulant therapy (ACT) to 46.5% of AF patients; in
      Phase 2, to 19.9 and 57.8%, respectively. Thus, 32.2% (Phase 1) and 22.2% (Phase
      2) of AF patients were not receiving any antithrombotic drug. Among AF patients
      with previous ischemic stroke (17.6%), only 49% (Phase 1) and 60.4% (Phase 2)
      were receiving ACT. As many as 34 and 22.6%, respectively, were not receiving any
      antithrombotic drug. After follow-up, a new acute embolic event was documented in
      5.6% of patients, 17% died. CONCLUSIONS: Anticoagulation is underused in AF
      patients and neither the fact of being treated by cardiologists in a University
      Hospital, nor the learning time-window of 1 year seemed to improve the
      antithrombotic care significantly.

PMID- 17186396
TI  - Does supervised exercise after deep venous thrombosis improve recanalization of
      occluded vein segments? A randomized study.
AB  - OBJECTIVES: The aim of the present study was to evaluate weather early supervised
      exercise improves recanalization of acute deep vein thrombosis (DVT) and reduces
      symptoms. PATIENTS AND METHODS: From September 2001 to March 2004, of 381
      patients, 72 eligible patients were included and with a mean age 54 +/- 14 years,
      39 (52%) men with deep vein thrombosis (DVT) proven with phlebography were
      randomized to: an exercise group (n = 36) receiving routine anticoagulation,
      class II compression stockings and additionally supervised exercise and a control
      group (n = 36) receiving the same therapy but no exercise. Patients were followed
      up during six months. Phlebography was scored initially and at six-months.
      RESULTS: There were at inclusion no differences between the two groups regarding
      age, body weight, body mass index (BMI), calf circumference of the affected leg,
      and overall quality of life estimated by visual analog scale (VAS)-scale. In both
      groups there were significant reductions regarding calf circumference in the
      affected leg compared to the inclusion time, both at one-month (P = 0.0012) and
      six month (P = 0.0002) follow-up. The degree of recanalization of the affected
      venous segments was high and did not differ between groups. There were no
      recurrent DVT or pulmonary emboli or other treatment complications in any
      individual during the six-month follow-up period. CONCLUSIONS: Early exercise did
      not acutely exacerbate the risk of complications in patients with DVT. No
      benefits of early exercise were seen regarding the degree of recanalization of
      the thrombi, or faster resolution of pain or swelling. Nevertheless, our study
      shows that early exercise/ambulation is safe in combination with anticoagulation
      and compression stockings for the majority of patients with DVT.

PMID- 17186397
TI  - Predictors and outcomes associated with gastrointestinal bleeding in patients
      with acute coronary syndromes.
AB  - BACKGROUND: Potent antiplatelet and anticoagulant agents along with early
      revascularization are increasingly used in patients hospitalized with acute
      coronary syndromes (ACS). An important complication associated with these
      therapies is gastrointestinal bleeding (GIB); yet, the predictors, optimal
      management, and outcomes associated with GIB in ACS patients are poorly studied.
      METHODS: We investigated the incidence, predictors, pathological findings, and
      clinical outcomes associated with GIB in patients with ACS hospitalized at a
      United States tertiary center between 1996 and 2001. RESULTS: Three percent
      (80/3,045) of ACS patients developed clinically significant GIB. Predictors of
      GIB were older age, female gender, non-smoking status, peak troponin I, and prior
      heart failure, diabetes, or hypertension. Patients with GIB were more critically
      ill with lower blood pressure and higher heart rates. GIB was associated with an
      increased need for transfusion, mechanical ventilation, and inotropes/pressors.
      In-hospital mortality was significantly higher in ACS patients with versus
      without GIB (36% vs. 5%, P < 0.001). Thirty patients (38%) with GIB underwent
      endoscopy with no procedural complications of death, arrhythmia, urgent ischemia,
      or hemodynamic deterioration. CONCLUSION: In patients with ACS, GIB is associated
      with older age, female sex, peak troponin I, non-smoking status, diabetes,
      hypertension, and heart failure. Hospital mortality is increased eightfold when
      ACS patients experience GIB. More studies are needed to establish the safety of
      and optimal timing of endoscopy in these patients.

PMID- 17186398
TI  - Elective transfer of two embryos: reduction of multiple gestations while
      maintaining high pregnancy rates.
AB  - PURPOSE: To determine if the elective transfer of two embryos reduced the
      incidence of multiple gestations while maintaining high pregnancy rates. METHODS:
      IVF patients and recipients of oocyte donation with an elective day-3 transfer of
      2 or 3 embryos were studied. RESULT(S): In IVF, the elective transfer of 2
      embryos resulted in similar pregnancy rate but significantly reduced the overall
      incidence of multiple gestations (20% versus 39%) when compared to the elective
      transfer of 3 embryos. Twin gestations decreased from 28% to 19%, and triplets
      significantly decreased from 9% to 1%. In oocyte donation, the elective transfer
      of 2 embryos resulted in similar pregnancy rate but also significantly reduced
      the overall incidence of multiple gestations (26% versus 48%), with twins
      decreasing from 34% to 24%, and with a significant reduction of triplets (13%
      versus 2%). CONCLUSIONS: In IVF and oocyte donation, the elective transfer of 2
      embryos resulted in similar pregnancy rates and significantly reduced multiple
      gestation rates when compared to the elective transfer of 3 embryos.

PMID- 17186399
TI  - Exposure-measurement error is frequently ignored when interpreting epidemiologic
      study results.
AB  - INTRODUCTION: One important source of error in study results is error in
      measuring exposures. When interpreting study results, one should consider the
      impact that exposure-measurement error (EME) might have had on study results.
      METHODS: To assess how often this consideration is made and the form it takes,
      journal articles were randomly sampled from original articles appearing in the
      American Journal of Epidemiology and Epidemiology in 2001, and the International
      Journal of Epidemiology between December 2000 and October 2001. RESULTS: Twenty
      two (39%) of the 57 articles surveyed mentioned nothing about EME. Of the 35
      articles that mentioned something about EME, 16 articles described qualitatively
      the effect EME could have had on study results. Only one study quantified the
      impact of EME on study results; the investigators used a sensitivity analysis.
      Few authors discussed the measurement error in their study in any detail.
      CONCLUSIONS: Overall, the potential impact of EME on error in epidemiologic study
      results appears to be ignored frequently in practice.

PMID- 17186400
TI  - Antimicrobial susceptibilities of Campylobacter jejuni isolates from hospitalized
      children in Athens, Greece, collected during 2004-2005.
AB  - A total of 170 Campylobacter jejuni strains isolated from the stool of children
      with clinical gastroenteritis, aged from 3 months to 14 years, were collected
      during a two-year period (2004-2005). From the 170 strains 30% were resistant to
      ciprofloxacin (MIC > or = 4 microg/ml), 55% to tetracycline (MIC > 8 microg/ml),
      13% to clindamycin (MIC > or = 8 microg/ml), 4% to ampicillin (MIC > 16
      microg/ml), 6% to erythromycin (MIC > or = 8 microg/ml), 4% to coamoxiclav (MIC >
      or = 16/8 microg/ml) and 0% to gentamicin. Compared to previous reports from
      Greece, the antimicrobial resistance rates to erythromycin, ampicillin and
      coamoxiclav remain low, while they are still high for tetracycline and
      ciprofloxacin. Considering similar reports from many other countries and the high
      incidence of Campylobacter gastroenteritis worldwide, the value of ciprofloxacin
      as a first choice drug in the empiric treatment of the infection is questionable.

PMID- 17186402
TI  - Occurrence of Leishmania DNA in urines of dogs naturally infected with
      leishmaniasis.

PMID- 17186401
TI  - Beat-by-beat cardiovascular index to predict unexpected intraoperative movement
      in anesthetized unparalyzed patients: a retrospective analysis.
AB  - OBJECTIVE: Unexpected intraoperative movement may be detrimental during delicate
      surgery. This study tested retrospectively an algorithm based on beat-by-beat
      circulatory variables (incorporated into a Cardiovascular depth of anesthesia
      index: CARDEAN in relationship to unexpected movement, and compared its
      performance to that of the electroencephalogram (EEG)-derived index: BIS-XP 4.0.
      METHODS: 40 ASA I or II patients presenting for knee surgery had EEG (BIS XP
      4.0), beat-by-beat (Finapres) finger non-invasive blood pressure (BP),
      conventional brachial BP and electrocardiogram (EKG) monitors attached.
      Anesthesia was induced and maintained with propofol and remifentanil. Before
      incision, the propofol concentration was set to maintain BIS < 60. From incision
      to emergence, the anesthesiologist was denied access to BIS or Finapres.
      Anesthesia adjustment was titrated at the discretion of the anesthesiologist
      according to conventional signs only: brachial BP, EKG, eyelash reflex, movement.
      Occurrences of movement and eye signs (divergence of eyeballs, tears, corneal
      reflex, eyelash reflex) were observed. The CARDEAN algorithm was written
      retrospectively and tested vs. BIS. RESULTS: 11 movements occurred in 8 patients.
      CARDEAN > 60 predicted movement in 30% of the cases, 15 to 274 s before movement
      (sensitivity: 100%, specificity: 95%; relative operating curve ROC = 0.98;
      prediction probability pk = 0.98). BIS > 60 predicted movement in 19% of cases
      (sensitivity: 64%; specificity: 94%, ROC: 0.85, pk: 0.85). CONCLUSION:
      Retrospectively, a cardiovascular index predicted unexpected intraoperative
      movements. Prospective validation is needed.

PMID- 17186403
TI  - Distribution and expression of recombinant plasmid encoding chicken interleukin
      2.
AB  - A plasmid DNA that encodes chicken interleukin-2 (pCI-ChIL-2-EGFP) was
      investigated for its distribution and expression after intramuscular (i.m.)
      injection in chickens. After the i.m. injection, serum distribution was
      detectable from 2 h post inoculation (p.i.), peaked at 8 h p.i., and disappeared
      at 7 days p.i. The plasmid DNA was also observed in several organs including
      heart, liver, lung, spleen, bursa and inoculated muscle at different time points,
      but at 19 days p.i. the plasmid DNA was not found in any organ except inoculated
      muscle. Fluorescence of enhanced green fluorescent protein (EGFP) was found in
      cytoplasm and nucleus of cultured Vero cells, chicken embryo fibroblasts and
      peripheral blood lymphocytes, which were transfected in vitro with the plasmid
      DNA or in vivo with Lipofectamine. The expression profile of the fusion gene
      (ChIL-2-EGFP) in vivo was measured by RT-PCR, ELISA and fluorescence microscopy.
      The EGFP expression was detected from 8 h p.i. to 14 days p.i. and peaked at 5
      days p.i., when the number of EGFP-expression myocytes was about 5% in the
      injected site. These results demonstrate that intramuscular administration of
      plasmid DNA leads to widespread distribution and long-term expression in vivo.

PMID- 17186404
TI  - Relationships between degree of azotaemia and blood pressure, urinary
      protein:creatinine ratio and fractional excretion of electrolytes in dogs with
      renal azotaemia.
AB  - Blood pressure (BP) was measured in 31 renal azotaemic dogs by oscillometric
      measurement at the posterior tibia artery, and urine and blood samples were
      collected. Haematology, blood chemistry and urinalysis were performed and urinary
      protein:creatinine ratio (UPC) and fractional excretions of electrolytes (FE(e))
      were calculated. The results showed that only 19% of dogs with renal azotaemia
      were hypertensive, whereas almost all of them had high urinary protein and
      electrolyte excretions. There was no association between BP, UPC and FE(e). A
      positive correlation was found between all pairs of electrolyte fractional
      excretions. When the severity of renal impairment was observed using plasma
      creatinine concentration, neither BP nor UPC was correlated. Only the FE( e ) was
      associated with the degree of azotaemia. The results suggest that dogs with renal
      azotaemia do not necessarily have hypertension. The fractional urinary excretion
      of electrolytes may be a good indicator for severity of renal dysfunction in
      azotaemic dogs.

PMID- 17186405
TI  - Acute-phase response alters the disposition kinetics of cefepime following
      intravenous administration to rabbits.
AB  - The effect of experimentally induced fever on the pharmacokinetics of cefepime
      administered intravenously at a dose of 75 mg/kg bw was studied in six healthy
      rabbits. The study was conducted in two consecutive phases, separated by a
      washout period of 2 weeks. Infection was induced by the intravenous inoculation
      of 5 x 10(8) cfu of Escherichia coli 24 h before the pharmacokinetic
      investigation was carried out. Serial blood samples for cefepime concentration
      determination were obtained for 48 h following drug administration. The
      concentrations of cefepime in the plasma were determined by a quantitative
      microbiological assay using an agar-gel diffusion method employing Bacillus
      subtilis ATCC 6633 as the test organism, with a level of detectability of
      approximately 0.10 microg/ml. Cefepime plasma concentrations versus time were
      evaluated by non-compartmental methods using WinNonLin. Cefepime was well
      tolerated and no serious adverse events were observed. Rectal temperature
      increased 1 degree C 24 h post injection in infected animals. Highly significant
      differences in the blood plasma concentrations of cefepime were observed between
      febrile and healthy animals at all the sampling times. This could explain the
      greater area under the plasma level-time curve of the drug in febrile compared
      with healthy animals. The results from pharmacokinetic calculations showed that
      both the distribution volume at steady state (V (dss)) and body clearance
      (CL(tot)) were affected in febrile as compared to healthy animals. The mean
      values of V (dss) and CL(tot) of cefepime in healthy rabbits were 1.168 L/kg and
      0.303 L/kg/h, respectively. As compared with healthy animals, the mean estimates
      of V (dss) (0.917 L/kg) and CL(tot) (0.205 L/kg per h) of cefepime were
      significantly lower, whereas t (1/2lambda), MRT and AUMC were significantly
      higher in febrile rabbits. It is concluded that, although experimental infection
      had an effect on the disposition kinetics of cefepime in healthy and febrile
      rabbits, this was not sufficiently pronounced to require alteration of the dosage
      during disease.

PMID- 17186406
TI  - A field study on the effect of some anthelmintics on cyathostomins of horses in
      sweden.
AB  - The objective of the study was to investigate different aspects on the efficacy
      of three anthelmintics on cyathostomin nematodes of Swedish horses. A faecal egg
      count reduction (FECR) test was performed on 26 farms. Horses were treated orally
      with recommended doses of ivermectin, pyrantel pamoate or fenbendazole. Faecal
      samples were collected on the day of deworming and 7, 14 and 21 days later. No
      resistance was shown against ivermectin; the FECR was constantly >99%. The effect
      of pyrantel was assessed as equivocal in 6 farms 14 days after treatment; the
      mean FECR was 99%. As many as 72% of the fenbendazole-treated groups met the
      criteria for resistance; the mean FECR was 86%, ranging from 56% to 100%. A re
      investigation of two farms where pyrantel resistance had been suspected clearly
      revealed unsatisfactory efficacy of pyrantel on one of these farms; the FECR
      varied from 72% to 89%. Twenty-six of the horses previously dosed with pyrantel
      or fenbendazole, and which still excreted >/=150 eggs per gram of faeces 14 days
      after treatment, were dewormed with ivermectin and fenbendazole or pyrantel in
      order to eliminate the remaining cyathostomins. A total of 13 cyathostomin
      species were identified from horses that initially received fenbendazole and
      seven species were identified from pyrantel-treated individuals. The egg
      reappearance period (ERP) following treatment with ivermectin and pyrantel was
      investigated on two farms. The shortest ERP after ivermectin treatment was 8
      weeks and after pyrantel was 5 weeks. We conclude that no substantial reversion
      to benzimidazole susceptibility had taken place, although these drugs have
      scarcely been used (<5%) in horses for the last 10 years. Pyrantel-resistant
      populations of cyathostomins are present on Swedish horse farms, but the overall
      efficacy of pyrantel is still acceptable.

PMID- 17186407
TI  - The gross anatomy of the cranial cervical ganglion in the guinea pig (Cavia
      porcellus).
AB  - The right and left cranial cervical ganglia in the heads of 10 adult guinea pigs
      (5 male, 5 female) were dissected in detail. The cranial cervical ganglion (CCG)
      was located on the caudo-ventral aspect of the distal ganglion of the vagus
      nerve, and medial to the digastric and styloglossal muscles. It was present also
      ventral to the tympanic bulla, ventro-lateral to the longus capitis muscle, and
      between the ascending pharyngeal and the internal carotid arteries. The branches
      of the CCG included the internal and external carotid nerves, the jugular nerve
      and connecting branches to the pharynx, vagus, glossopharyngeal, accessory,
      cranial laryngeal, first and second cervical nerves, and vessels in the carotid
      body region. The number of nerves ramifying from the CCG of the guinea pig varied
      among cases. Compared to other species, there are also differences in the number
      of nerve branches and the course patterns. No sex differences are present as far
      as the guinea pig CCG is concerned.

PMID- 17186408
TI  - Evaluation of the effects of the sedation with azaperone/acepromazine and
      immobilization with guaiphenesin/thiopentone in mules.

PMID- 17186409
TI  - Recombinant antigen-based latex agglutination test for rapid serodiagnosis of
      leptospirosis.
AB  - A rapid recombinant antigen-based latex agglutination test (LAT) has been
      developed to detect specific anti-leptospiral antibodies from human and dog sera.
      The recombinant LipL32 antigen developed and used for detecting the antibodies is
      specific in detection of the pathogenic serovars of Leptospira as the expression
      of the LipL32 antigen is restricted only to the pathogenic leptospires. The
      sensitized latex beads are stable and could be stored at 4 degrees C for more
      than three months without showing loss of activity for both weakly and strongly
      positive samples. The test is found to be sensitive, specific and accurate as
      compared to the standard microscopic agglutination test (MAT). Moreover, the
      recombinant antigen-coated latex beads could detect the specific anti-leptospiral
      antibodies in the acute phase of the illness. The test is simple and inexpensive,
      and is rapid in the management of large numbers of patients.

PMID- 17186410
TI  - Immunohistochemical study of phospho-Stat3-ser727 expression in feline mammary
      gland tumours.
AB  - We describe the expression of pStat3-ser727 (signal transducer and activator of
      transcription 3 phosphorylated on serine 727) in normal, hyperplastic and
      neoplastic feline mammary gland tissue assessed by immunohistochemistry in 56
      cats. The samples included 4 normal mammary non-lactating tissues, 13
      hyperplastic lesions (9 lobular and 4 fibroepithelial) and 39 tumours (6 benign
      and 33 carcinomas). For immunohistochemistry, tissue sections were incubated with
      anti-pStat3-ser727 monoclonal antibodies and visualized with EnVision-DAB
      polymer. pStat3-ser727 positivity was quantified in a semi-quantitative manner,
      differentiating cytoplasmic and nuclear localization. Intense anti-pStat3-ser727
      immunoreactivity was detected in epithelial neoplastic cells and in the fibro
      component in two fibroepithelial hyperplastic lesions. The immunostaining was dot
      like in the cytoplasm and homogeneous in the nuclei in both benign and malignant
      lesions. Statistically significant relations were observed between nuclear
      expression of pStat3-ser727 and the pleomorphism score (p = 0.006), mitotic
      activity (p < 0.0001), and histological grade (p < 0.0001). In contrast, no
      significant correlations were observed for cytoplasmic pStat3-ser727. These
      findings add new and interesting information on the potential role of the
      phosphorylated form of Stat3 in malignant lesions.

PMID- 17186411
TI  - Echinococcus granulosus of buffalo in India: partial characterization of
      excretory-secretory and germinal membrane antigens.

PMID- 17186412
TI  - Acute liver failure in pregnancy associated with maternal MCAD deficiency.
AB  - In recent years the association between severe pregnancy complications and fetal
      fatty acid oxidation (FAO) disorders has been reported. However, there are few
      descriptions of a maternal FAO disorder leading to these complications. We
      describe acute liver failure associated with an undiagnosed maternal medium-chain
      acyl-CoA dehydrogenase (MCAD) deficiency. The previously healthy proband
      presented at the 39th week with an itchy rash, palmar erythema and trace
      proteinuria; she was admitted onto a maternity ward. Acute fatty liver was
      suspected from the blood tests and a Caesarean section was performed, delivering
      a healthy boy. Cord blood samples were taken at delivery as part of an ongoing
      research project. The analysis of the cord blood sample showed a high
      concentration of octanoylcarnitine of 2.3 micromol/L (reference <0.1), suggesting
      a possible fatty acid oxidation disorder. However, subsequent acylcarnitine
      analyses of the baby's blood showed a normal pattern. The proband was further
      evaluated by urine organic acids and acylcarnitine profile. Elevated
      concentrations of hexanoylglycine in urine and octanoylcarnitine in blood spots
      were found, consistent with a diagnosis of MCAD deficiency. Mutation analyses
      confirmed that she was homozygous for c.985A>G (K329E). Even though these
      pregnancy complications are rare and it is not possible to affirm that the
      proband's acute liver failure was secondary to an undiagnosed MCAD deficiency, it
      seems likely.

PMID- 17186414
TI  - An OTC deficiency 'phenocopy' in association with Klinefelter syndrome.
AB  - Late-onset urea cycle disorder in a 20-month-old boy is unusually associated with
      Klinefelter syndrome with a 47XXY karyotype. We record the typical clinical and
      biochemical findings of ornithine transcarbamylase (OTC) deficiency in a young
      boy with a short history of recurrent vomiting, self mutilating behaviour,
      lethargy, ataxia and seizures. Laboratory studies showed hyperammonaemia and
      orotic aciduria, with normal citrulline and other urea cycle amino acids.
      Unfortunately, a liver biopsy for OTC activity measurement was refused by the
      parents. A rapid reversal of phenotype was seen on the introduction of a low
      protein diet with accompanying benzoate and phenylbutyrate administration.
      Linkage studies suggested the inheritance of two X chromosomes, which was
      confirmed by karyotype analysis. Sequencing of all exons and immediate splice
      site regions revealed no sequence alterations in these sections of the OTC gene.
      A search for skewing of X-inactivation in the liver was not possible but we did
      show a random pattern of X-inactivation in leukocytes. The possibility of
      maternal X chromosome iso-disomy in our patient was discounted by microsatellite
      analysis, which revealed the inheritance of two independent X chromosomes.
      Mutation analysis in the OTC gene has shown that approximately 20% of patients
      with liver biopsy confirmed OTC deficiency do not have mutations in the coding or
      immediate splice-site sequences of this gene. Their classification as OTC
      phenocopies remains speculative, awaiting clarification of the underlying DNA
      alteration. We report on the novel association of OTC deficiency and Klinefelter
      syndrome with the additional interest of a probable unusual genetic defect
      underlying the OTC abnormality.

PMID- 17186413
TI  - Clinical, enzymatic and molecular characterization of nine new patients with
      malonyl-coenzyme A decarboxylase deficiency.
AB  - We report nine new patients with malonic aciduria associated with enzyme
      confirmed malonyl-CoA decarboxylase (MCD) deficiency in eight. Clinical details
      were available on eight, and molecular genetic characterization was obtained for
      nine. As for 15 previously described patients, cardinal clinical manifestations
      included developmental delay and cardiomyopathy; metabolic perturbations (e.g.
      acidosis) and seizures, however, were infrequent or not observed in our patients.
      For all, detection of elevated malonic acid in urine (+/- increased C3DC
      acylcarnitine by analysis employing tandem mass spectrometry) led to pursuit of
      enzyme studies. MCD activities (nmol/h PER mg protein) revealed: control (n =
      22), 16.2 +/- 1.8 (SEM; range 5.7-46.2); patients (n = 8, assayed in duplicate),
      1.7 +/- 0.3 (10% of parallel control; range 0.6-2.8). Molecular characterization
      by DNA sequence analysis and multiplex ligation-dependent probe amplification
      revealed nine novel mutations (c.796C>T; p.Gln266X, c.481delC; p.Leu161CysfsX18,
      c.1367A>C; p.Tyr456Ser, c.1319G>T; p.Ser440Ile, c.1430C>T; p.Ser477Phe, c.899G>T;
      p.Gly300Val, c.799-1683_949-1293del3128, and two other large genomic deletions
      comprising exons 1 or the complete gene) and two known mutations in the MLYCD
      gene. Our findings increase the number of enzyme-confirmed MCD-deficient patients
      by >50%, and expand our understanding of the phenotypic and molecular
      heterogeneity of this rare disorder.

PMID- 17186415
TI  - Borderline mental development in a congenital disorder of glycosylation (CDG)
      type Ia patient with multisystemic involvement (intermediate phenotype).
AB  - CDG Ia (phosphomannomutase deficiency) has a wide clinical spectrum with the most
      severe affected patients having multisystemic disease in addition to severe
      nervous system involvement. We report a patient with CDG Ia and an intermediate
      phenotype due to mild neurological impairment and borderline cognitive abilities
      despite the occurrence of typical extraneurological symptoms. These included
      liver involvement, coagulopathy and failure to thrive with enteropathy. Genotype
      analyses showed that he was compound heterozygous for T237R/C241S mutations. This
      observation underlines that the CDG Ia clinical spectrum may include
      intraindividual variability that might reflect different degrees of glycosylation
      abnormalities among distinct body compartments. CDG Ia should be considered in
      cases of unexplained liver involvement and/or enteropathy in patients with mild
      developmental delay and subtle neurological signs.

PMID- 17186416
TI  - A rationale for cystine supplementation in severe homocystinuria.
AB  - Previous studies have shown that the thiol redox, as measured by the ratio of
      free/bound cyst(e)ine in unaffected individuals, remains relatively constant. In
      severe homocystinuria (HCU) where cyst(e)ine moieties are significantly reduced,
      this redox is only restored when homocyst(e)ine moieties are also taken into
      account. This appears to stem from an increase in the free/bound homocyst(e)ine
      ratio with free homocystine acting as a surrogate for free cystine. We examined
      these ratios in 47 patients (two with a cobalamin C defect, two with
      methylenetetrahydrofolate reductase deficiency, 16 with pyridoxine-responsive HCU
      and 27 with pyridoxine-nonresponsive HCU). Comparing free/bound homocyst(e)ine
      ratios to the total cysteine concentration indicates a relative increase of free
      homocystine as total cysteine concentrations fall below 170 micromol/L. This
      provides a rationale and treatment algorithm for cyst(e)ine supplementation in
      homocystinuria.

PMID- 17186417
TI  - Bond-based global and local (bond, group and bond-type) quadratic indices and
      their applications to computer-aided molecular design. 1. QSPR studies of diverse
      sets of organic chemicals.
AB  - The concept of atom-based quadratic indices is extended to a series of molecular
      descriptors (MDs) (both total and local) based on adjacency between edges. The
      kth edge-adjacency matrix (E ( k )) denotes the matrix of bond-based quadratic
      indices (non-stochastic) with respect to the canonical basis set. The kth
      "stochastic" edge-adjacency matrix, ES ( k ), is here proposed as a new molecular
      representation easily calculated from E ( k ). Then, the kth stochastic bond
      based quadratic indices are calculated using ES ( k ) as operators of quadratic
      transformations. The study of six representative physicochemical properties of
      octane isomers was used to compare the ability of both series of MDs to produce
      significant quantitative structure-property relationship (QSPR) models. Moreover,
      the general performance of the new MDs in this QSPR study has been evaluated with
      respect to other 2D/3D well-known sets of indices and the obtained results shown
      a quite satisfactory behavior of the present method. The novel bond-level MDs
      were also used for the description and prediction of the boiling point of 28
      alkyl-alcohols and to the modeling of the specific rate constant (log k) of 34
      derivatives of 2-furylethylenes. These models were statistically significant and
      showed very good stability to data variation in leave-one-out (LOO) cross
      validation experiment. The comparison with other approaches (edge- and vertices
      based connectivity indices, total and local spectral moments, and quantum
      chemical descriptors as well as E-state/biomolecular encounter parameters) expose
      a good behavior of our method in this QSPR studies. The approach described in
      this report appears to be a very promising structural invariant, useful for
      QSPR/QSAR studies, similarity/diversity analysis, and computer-aided "rational"
      molecular (drug) design.

PMID- 17186419
TI  - Trace elements and cancer risk: a review of the epidemiologic evidence.
AB  - Worldwide, there are more than 10 million new cancer cases each year, and cancer
      is the cause of approximately 12% of all deaths. Given this, a large number of
      epidemiologic studies have been undertaken to identify potential risk factors for
      cancer, amongst which the association with trace elements has received
      considerable attention. Trace elements, such as selenium, zinc, arsenic, cadmium,
      and nickel, are found naturally in the environment, and human exposure derives
      from a variety of sources, including air, drinking water, and food. Trace
      elements are of particular interest given that the levels of exposure to them are
      potentially modifiable. In this review, we focus largely on the association
      between each of the trace elements noted above and risk of cancers of the lung,
      breast, colorectum, prostate, urinary bladder, and stomach. Overall, the evidence
      currently available appears to support an inverse association between selenium
      exposure and prostate cancer risk, and possibly also a reduction in risk with
      respect to lung cancer, although additional prospective studies are needed. There
      is also limited evidence for an inverse association between zinc and breast
      cancer, and again, prospective studies are needed to confirm this. Most studies
      have reported no association between selenium and risk of breast, colorectal, and
      stomach cancer, and between zinc and prostate cancer risk. There is compelling
      evidence in support of positive associations between arsenic and risk of both
      lung and bladder cancers, and between cadmium and lung cancer risk.

PMID- 17186418
TI  - Transient caloric restriction and cancer risk (The Netherlands).
AB  - Over the past century, many animal experiments have shown that caloric
      restriction can reduce the risk of cancer, a finding that proved to be highly
      reproducible. Many papers have been published on its potential for human health,
      but until know little evidence is available on its actual effects in humans. In
      Utrecht, The Netherlands, we have been investigating the effects of the 1944-1945
      Dutch famine on breast cancer risk factors and breast cancer risk, and
      paradoxically the relatively short-term famine seemed to be related to increased
      breast cancer risk in later life. One of the differences between the famine
      situation and the large body of evidence from animal experiments is the duration
      of caloric restriction. Almost all animal experiments investigated sustained
      caloric restriction and information on the effects of short-term transient
      caloric restriction is very scarce. A search in the literature identified some
      animal experiments on short-term transient caloric restriction and these seemed
      to be at least supportive to the famine findings. Because caloric restriction in
      humans for preventive health measures would be mostly short-term, it is important
      to extend animal research on short-term caloric restriction.

PMID- 17186421
TI  - Tools for health: the efficacy of a tailored intervention targeted for
      construction laborers.
AB  - OBJECTIVES: Novel approaches to worksite health promotion are needed for high
      risk workers who change job sites frequently, and thus may have limited access to
      worksite health promotion efforts. The objective of this study was to test a
      behavioral intervention among construction laborers. METHODS: Using a randomized
      controlled design, we tested the efficacy of a tailored telephone-delivered and
      mailed intervention to promote smoking cessation and increased fruit and
      vegetable consumption (n = 582). RESULTS: At baseline, 40% of control group
      participants and 45% of intervention group participants reported using any
      tobacco in the last seven days. At final, 8% of baseline cigarette smokers in the
      control group had quit, compared to 19% in the intervention group (p = 0.03). In
      both groups, the mean consumption of fruits and vegetables at baseline was over
      five servings per day. At final, the intervention group had increased consumption
      by approximately one and one-half servings, compared to a slight decrease in
      consumption in the control group (p < 0.001). CONCLUSIONS: A tailored
      intervention can be efficacious in promoting tobacco use cessation and increased
      fruit and vegetable consumption among construction laborers, a high-risk, mobile
      workforce.

PMID- 17186420
TI  - Serum organochlorines and breast cancer: a case-control study among African
      American women.
AB  - This population-based case-control study of African-American women (355 breast
      cancer case patients, 327 controls) examined the association between breast
      cancer and circulating levels of PCBs and dichlorodiphenyldichloroethene (DDE), a
      metabolite of DDT. Case patients were diagnosed with invasive breast carcinoma
      and interviewed between June 1995 and July 1998, and control subjects were
      identified by random digit dialing methods. Serum levels of DDE and total PCBs
      were adjusted for total lipid content. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated using multivariable unconditional logistic
      regression methods. Effect modification by tumor receptor status and cancer
      treatment was investigated. Breast cancer risk was not associated with increasing
      quintiles of lipid-adjusted PCBs or DDE (highest versus lowest quintile adjusted
      for age, body mass index (BMI) and breastfeeding for DDE: OR = 1.02, 95% CI =
      (0.61, 1.72), p-trend = 0.74; for PCBs: OR = 1.01, 95% CI = (0.63, 1.63), p-trend
      = 0.56). Risk did not differ by strata of BMI, breastfeeding, parity, menopausal
      status or tumor receptor status. This study, the largest study of African
      American women to date, does not support a role of DDE and total PCBs in breast
      cancer risk at the levels measured.

PMID- 17186422
TI  - Which women aren't getting mammograms and why? (United States).
AB  - OBJECTIVE: This study investigates why women who reported no recent mammogram did
      not get the test. METHODS: Using data from the 2000 National Health Interview
      Survey (NHIS), we examine correlates of mammography use among women 40 years and
      older (n = 10,212), with particular focus on the 30% (n = 3,188) who reported no
      recent mammogram. Non-screening is examined in the context of two important
      correlates of mammography use-access to health care and a physician's
      recommendation to get a mammogram. RESULTS: In total, 80% of non-screeners who
      reported having access to healthcare did not receive a recommendation for a
      mammogram. Women age 65 years and older were more likely than younger women to
      report not receiving a recommendation (OR 1.77, 95% CI 1.25-2.50). For women who
      reported having access, non-screening was significantly more likely among younger
      women (40-49), those with less education, incomes less than 20,000 dollars,
      residence outside Metropolitan Statistical Areas (MSAs) and no family history of
      breast cancer. Among women with access problems, those who had not visited a
      primary care provider in the past year were much more likely to be non-screeners
      (80%) compared with those who had seen a provider (46%). Among women with access,
      those who reported put it off as the main reason for non-screening were
      significantly more likely to be younger and to be born in the U.S. than women who
      said that they didn't know they needed a mammogram. CONCLUSIONS: Most non
      screeners report not receiving a physician recommendation for mammography.
      Although a minority reported access problems, the effect of lacking access on
      utilization was strong and is accentuated when women without access do not see a
      doctor. These findings confirm the importance of a mammography recommendation and
      raise questions concerning whether this information is being conveyed by
      physicians or heard by patients.

PMID- 17186423
TI  - Evaluation of ecological and in vitro effects of boron on prostate cancer risk
      (United States).
AB  - OBJECTIVE: To determine: (1) the correlation of prostate cancer incidence and
      mortality with groundwater boron and selenium concentrations; and (2) the impact
      of boron on prostate cancer cell proliferation during co-treatment with
      alternative chemo-preventative agents, along with boron pre-treatment effects on
      cell sensitivity to ionizing radiation. METHODS: For regression analysis, data on
      prostate cancer incidence and mortality were obtained from the Texas Cancer
      Registry, while groundwater boron and selenium concentrations were derived from
      the Texas Water Development Board. Cultured DU-145 prostate cancer cells were
      used to assess the impact of boric acid on cell proliferation when applied in
      combination with selenomethionine and genistein, or preceding radiation exposure.
      RESULTS: Groundwater boron levels correlated with a decrease in prostate cancer
      incidence (R = 0.6) and mortality (R = 0.6) in state planning regions, whereas
      selenium did not (R = 0.1; R = 0.2). Growth inhibition was greater during
      combined treatments of boric acid and selenomethionine, or boric acid and
      genistein, versus singular treatments. 8-day boric acid pre-exposure enhanced the
      toxicity of ionizing radiation treatment, while dose-dependently decreasing the
      expression of anti-apoptotic protein Bcl-2. CONCLUSIONS: Increased groundwater
      boron concentrations, across the state of Texas, correlate with reduced risk of
      prostate cancer incidence and mortality. Also, boric acid improves the anti
      proliferative effectiveness of chemo-preventative agents, selenomethionine and
      genistein, while enhancing ionizing radiation cell kill.

PMID- 17186424
TI  - Manganese superoxide dismutase polymorphism and risk of skin cancer (United
      States).
AB  - OBJECTIVE: We assessed whether the functional V16A polymorphism in the MnSOD gene
      is associated with skin cancer risk. METHODS: We conducted a nested case-control
      study (219 melanoma, 286 squamous cell carcinoma (SCC), and 300 basal cell
      carcinoma (BCC) cases, and 873 matched controls) within the Nurses' Health Study.
      Genotyping was performed by the 5' nuclease assay (TaqMan). We used logistic
      regression to model the association between the genotype and skin cancer risk.
      RESULTS AND CONCLUSIONS: Overall, there was no significant association between
      this polymorphism and the risk of each type of skin cancer. No significant
      interaction was observed between this polymorphism and sunburn history and
      constitutional susceptibility on skin cancer risk. For interactions between
      intakes of alpha-carotene and beta-carotene and the MnSOD polymorphism on SCC,
      the inverse association of intake of either carotene with SCC risk was limited to
      the Val carriers, whereas no association was observed among women with the AA
      genotype. We observed an interaction between total vitamin C intake and the MnSOD
      polymorphism on melanoma risk. No interaction was observed for the intakes of
      other carotenoids, vitamin E, and vitamin A. Further research is needed to
      confirm these possible associations.

PMID- 17186426
TI  - An evaluation of spatial and multivariate covariance among childhood cancer
      histotypes in Texas (United States).
AB  - BACKGROUND: Spatial modeling of rare diseases, such as childhood cancer, has been
      hampered by imprecise risk estimates. Recent developments in Bayesian
      hierarchical modeling include the ability to adjust a disease risk estimate to be
      fully conditional for covariance among neighboring locations and for covariance
      among multiple diseases within each location. This joint modeling approach is
      called Multivariate Intrinsic Conditional Autoregressive. The objective of this
      study was to evaluate the spatial and histotype covariance among childhood cancer
      histotypes, in Texas. Results will be valuable for selecting appropriate models
      to support more specific etiologic studies of environmental factors for childhood
      cancer. METHODS: County level standard morbidity ratios for 13 childhood cancer
      histotype groups were estimated using Multivariate Intrinsic Conditional
      Autoregressive modeling and the results compared to results from two reduced
      models. The two reduced models were the base model specified with zero spatial
      covariance and the base model specified with zero histotype covariance. The
      results were compared using the Deviance Information Criterion and Geographical
      Information System techniques were used to compare patterns of standard morbidity
      ratios. RESULTS: Including histotype covariance greatly improved the Deviance
      Information Criterion and including spatial covariance produced a moderate
      improvement. Parameter evaluation by GIS techniques showed that excluding
      histotype covariance resulted in marked shrinkage of the risk estimates.
      CONCLUSIONS: Investigation of childhood cancer could benefit by incorporating
      histotype covariance into environmental modeling.

PMID- 17186425
TI  - Wine and other alcohol consumption and risk of ovarian cancer in the California
      Teachers Study cohort.
AB  - OBJECTIVE: Whether alcohol consumption influences ovarian cancer risk is unclear.
      Therefore, we investigated the association between alcohol intake at various ages
      and risk of ovarian cancer. METHODS: Among 90,371 eligible members of the
      California Teachers Study cohort who completed a baseline alcohol assessment in
      1995-1996, 253 women were diagnosed with epithelial ovarian cancer by the end of
      2003. Multivariate Cox proportional hazards regression analysis was performed to
      estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS:
      Consumption of total alcohol, beer, or liquor in the year prior to baseline, at
      ages 30-35 years, or at ages 18-22 years was not associated with risk of ovarian
      cancer. Consumption of at least one glass per day of wine, compared to no wine,
      in the year before baseline was associated with increased risk of developing
      ovarian cancer: RR = 1.57 (95% CI 1.11-2.22), P (trend) = 0.01. The association
      with wine intake at baseline was particularly strong among peri-/post-menopausal
      women who used estrogen-only hormone therapy and women of high socioeconomic
      status. CONCLUSIONS: Alcohol intake does not appear to affect ovarian cancer
      risk. Constituents of wine other than alcohol or, more likely, unmeasured
      determinants of wine drinking were associated with increased risk of ovarian
      cancer.

PMID- 17186427
TI  - Clinical outcomes and cost analysis of a "fast track" postoperative care pathway
      for ileal pouch-anal anastomosis: a case control study.
AB  - PURPOSE: Traditional length of hospital stay after ileal pouch-anal anastomosis
      is 8 to 15 days. Fast track rehabilitation programs reduce stay, but there are
      concerns that readmission and complication rates may be increased. This study
      evaluated a fast track pathway after ileoanal pouch surgery. METHODS: One hundred
      three consecutive patients underwent ileal pouch-anal anastomosis on two
      colorectal services using a fast track protocol with early ambulation, diet, and
      defined discharge criteria. Direct hospital costs and 30-day and long-term
      complication data were collected. Patients were matched to controls managed with
      traditional care pathways by other colorectal staff. RESULTS: Matching was
      established for 97 patients. Fast track patients had shorter hospital stay than
      controls (median 4 vs. 5 days; mean 5.0 vs. 5.9, P = 0.012). Readmission and
      recurrent operation rates were similar (24 vs. 20 percent, P = 0.49, and 9 vs. 10
      percent, P = 0.8, fast track vs. control, respectively). Median direct costs per
      patient (US$) within 30 days were lower with fast track (5692 vs. 6672, P =
      0.001), primarily because of reductions in postoperative management expenses.
      Complication rates, including pouch failure, bowel obstruction, pouchitis, and
      anastomotic stricture were comparable. Early discharge (< or = 5 days from
      surgery) occurred in 79 (77 percent) fast track patients. Failure with early
      discharge was associated with male gender, reoperations, and anastomotic
      complications. CONCLUSIONS: Fast track protocol after ileoanal pouch surgery
      reduces length of stay and hospital costs without increasing complication rates.
      Successful early discharge usually signals a benign postoperative course.

PMID- 17186428
TI  - Genetic stock identification of chum salmon in the Bering Sea and North Pacific
      Ocean using mitochondrial DNA microarray.
AB  - A newly developed DNA microarray was applied to identify mitochondrial (mt) DNA
      haplotypes of more than 2200 chum salmon in the Bering Sea and North Pacific
      Ocean in September 2002 and also 2003, when the majority of maturing fish were
      migrating toward their natal river. The distribution of haplotypes occurring in
      Asian and North American fish in the surveyed area was similar in the 2 years. A
      conditional maximum likelihood method for estimation of stock compositions
      indicated that the Japanese stocks were distributed mainly in the north central
      Bering Sea, whereas the Russian stocks were mainly in the western Bering Sea. The
      North American stocks were abundant in the North Pacific Ocean around the
      Aleutian Islands. These results indicate that the Asian and North American stocks
      of chum salmon are nonrandomly distributed in the Bering Sea and the North
      Pacific Ocean, and further the oligonuleotide DNA microarray developed by us has
      a high potential for identification of stocks among mixed ocean aggregates of
      high-seas chum salmon.

PMID- 17186430
TI  - Is nasogastric or nasojejunal decompression necessary after gastrectomy? A
      prospective randomized trial.
AB  - BACKGROUND: Nasogastric decompression has been routinely used in most major
      abdominal operations to prevent the consequences of postoperative ileus. The aim
      of the present study was to assess the necessity for routine prophylactic
      nasogastric or nasojejunal decompression after gastrectomy. METHODS: A
      prospective randomized trial included 84 patients undergoing elective partial or
      total gastrectomy. The patients were randomized to a group with a postoperative
      nasogastric or nasojejunal tube (Tube Group, n = 43) or to a group without a tube
      (No-tube Group, n = 41). Gastrointestinal function, postoperative course, and
      complications were assessed. RESULTS: No significant differences in postoperative
      mortality or morbidity, especially fistula or intra-abdominal sepsis, were
      observed between the groups. Passage of flatus (P < 0.01) and start of oral
      intake (P < 0.01) were significantly delayed in the Tube Group. Duration of
      postoperative perfusion (P = 0.02) and length of hospital stay (P = 0.03) were
      also significantly longer in the Tube Group. Rates of nausea and vomiting were
      similar in the two groups. Moderate to severe discomfort caused by the tube was
      observed in 72% of patients in the Tube Group. Insertion of a nasogastric or
      nasojejunal tube was necessary in 5 patients in the No-tube Group (12%).
      CONCLUSIONS: Routine prophylactic postoperative nasogastric decompression is
      unnecessary after elective gastrectomy.

PMID- 17186429
TI  - Profiling transcriptome complexity and secondary metabolite synthesis in a
      benthic soft coral, Sinularia polydactyla.
AB  - Sinularia polydactyla, an abundant Indo-Pacific soft coral species, exhibits
      biochemical phenotypic plasticity, prompting investigations into differences in
      mRNA diversity and complexity in response to predation stress. Changes in
      transcriptome complexity of S. polydactyla cDNA libraries were measured using
      reannealing rate assays that employ an informatics-based analysis of kinetic
      profiles. This method allows for quick, high-throughput analysis of sequence
      complexity and has been used to compare transcriptome-level differences in other
      marine invertebrates. Here, S. polydactyla colonies were transplanted between two
      sites exhibiting high and low predation levels. Statistically significant
      differences between bite scar counts found on different transplant groups suggest
      site-specific variation in predation. Changes in mRNA pool complexity were
      quantified to indicate shifts in secondary metabolite concentration between
      treatment groups. Examining the complexity of the mRNA pool in this soft coral is
      one of the first steps toward understanding the mechanisms of phenotypic
      plasticity at a biochemical and molecular level.

PMID- 17186432
TI  - Clinicopathological study of gastric metastases.
AB  - OBJECTIVE: The stomach is an uncommon site for metastasis, and most of the
      reported examples would appear to have been caused by direct invasion from
      primary malignancies. Metastases to the stomach are extremely rare, and few cases
      have been reported in the literature. This study was intended to evaluate the
      character of and the prognosis for metastasized tumors of the stomach. METHOD: We
      evaluated the medical records of patients who had presented at the National
      Taiwan University Hospital over a period of 10 years prior to writing who had
      malignancies and had developed metastasis to the stomach. We evaluated the
      histology, initial presentations, imaging findings, lesion locations, treatment
      courses, and overall patient survival. RESULT: From October 1995 to October 2004
      inclusively, only 18 patients featuring known malignancies with metastases to the
      stomach were found. The male to female ratio was 10:8. The initial symptom for 13
      study patients was bleeding from the metastasis tumors, and the remaining 5
      experienced a variety of other symptoms. The site of the metastasis was the
      gastric body for 9 patients, the gastric antrum for 6, the cardia or fundus for
      2, and the entire stomach for 1. The time period elapsing between the emergence
      of the primary malignancy and the gastric metastasis was less than 2 years for 3
      patients and about 5-6 years for another 2 patients. The mean time elapsing from
      the diagnosis of gastric metastasis to patient death was quite short, namely,
      about 6 months. CONCLUSION: Carcinomas featuring gastric metastasis are typically
      very rare and reveal a rather poor prognosis. The results of this preliminary
      study suggest that most treatment for these patients seemed to provide only
      symptomatic relief but did not prove helpful for long-term survival.

PMID- 17186434
TI  - Reaction to "the darkest hour".

PMID- 17186433
TI  - Computer-enhanced robotic surgery in gynecologic oncology.
AB  - BACKGROUND: This study aimed to report the computer-enhanced robotic surgery
      experience of the authors' gynecologic oncology division. METHODS: From January
      2001 to August 2006, 41 patients underwent laparoscopic surgery by our
      gynecologic oncology service using a computer-enhanced surgical robot. This
      report describes a retrospective review of these patients. RESULTS: The patients
      ranged in age from 27 to 77 years (mean, 44.2 years), in weight from 44 to 131 kg
      (mean, 72.1 kg), in operative time from 1 h and 50 min to 9 h (mean, 5 h and 2
      min), and in estimated blood loss from 50 to 1,500 ml (mean, 253 ml). Of the 20
      patients with gynecologic malignancies, 14 had cervical cancer. A total of 21
      patients had benign indications for surgery. Complications included shoulder
      palsy, robot failure, colotomy, bradycardia, and intraabdominal bleeding
      requiring minilaparotomy and ligation of a bleeding pedicle. CONCLUSION: This
      case series is one of the first to report the use of a computer-enhanced surgical
      robot in gynecologic oncology. This approach proved to be feasible and well
      tolerated in this series of patients and deserves further study for clarification
      of its indications, benefits, and safety.

PMID- 17186435
TI  - Youth-parent communication.

PMID- 17186436
TI  - Herbal and natural medicines in the Latino community.

PMID- 17186437
TI  - Teaching medical students trigger point techniques.

PMID- 17186438
TI  - Making it personal; mentoring future family docs.

PMID- 17186439
TI  - Encouragement: giving "heart" to our learners in a competency-based education
      model.

PMID- 17186441
TI  - The attending and the octogenarian.

PMID- 17186440
TI  - A gain in cultural competence through an international acupuncture elective.
AB  - OBJECTIVE: This study describes an international acupuncture elective and its
      impact on medical students' development of cultural competence. METHODS:
      Collaborating with Chinese colleagues, we created a 4-week elective that teaches
      medical students about acupuncture in its native cultural environment. Three
      focus groups were conducted to elicit students' experiences. RESULTS: Students'
      reflections indicated that studying an alternative medical system in its own
      cultural setting helped them become open to other medical beliefs and realize the
      importance of culture in health care delivery. Further, being linguistically
      isolated allowed students to personally experience what it is like for those
      patients with limited language proficiency. CONCLUSION: Studying an alternative
      medical system while immersed in another culture maybe an effective way to
      enhance cultural competence.

PMID- 17186442
TI  - Lights, camera, action: using film to teach the ACGME competencies.

PMID- 17186443
TI  - Family medicine curriculum resource project: overview.
AB  - In 2000, the Health Resources and Services Administration, in the interest of
      fostering curriculum reform in medical schools, awarded a 4-year contract to the
      Society of Teachers of Family Medicine to develop a curricular resource. The
      contract directed development of a multi-part resource aimed at (1) preclerkship
      prerequisites for third-year clerkships in collaboration with internal medicine
      and pediatrics, (2) the family medicine clerkship, (3) post-clerkship preparation
      for residency training, and (4) specific special topic areas of importance to the
      government. The Family Medicine Curriculum Resource (FMCR) was produced by
      primary care educators, with day-to-day direction from an executive committee and
      overall oversight by an advisory committee. The FMCR was built around a
      theoretical framework to link medical student competencies with the Accreditation
      Council for Graduate Medical Education (ACGME) competencies for residency
      training. Considerable energy throughout development of the FMCR was devoted to
      obtaining input from potential end-user audiences through an active dissemination
      effort.

PMID- 17186444
TI  - The family medicine curriculum resource project structural framework.
AB  - BACKGROUND: In the original contract for the Family Medicine Curricular Resource
      Project (FMCRP), the Health Resources and Services Administration (HRSA),
      Division of Medicine and Dentistry, charged the FMCRP executive committee with
      reviewing recent medical education reform proposals and relevant recent curricula
      to develop an analytical framework for the project. METHODS: The FMCRP executive
      and advisory committees engaged in a review and analysis of a variety of
      curricular reform proposals generated during the last decade of the 20th century.
      At the same time, in a separate and parallel process, representative individuals
      from all the family medicine organizations, all levels of learners, internal
      medicine and pediatric faculty, and the national associations of medical and
      osteopathic colleges (Association of American Medical Colleges and the American
      Association of Colleges of Osteopathic Medicine) were involved in group
      discussions to identify educational needs for physicians practicing in the 21st
      century. RESULTS: After deliberation, a theoretical framework was chosen for this
      undergraduate medical education resource that mirrors the Accreditation Council
      for Graduate Medical Education (ACGME) competencies, a conceptual design
      originated for graduate medical education. DISCUSSION: In addition to reflecting
      the current environment calling for change and greater accountability in medical
      education, use of the ACGME competencies as the theoretical framework for the
      FMCR provides a continuum of focus between the two major segments of physician
      education: medical school and residency.

PMID- 17186445
TI  - Prerequisite competencies for third-year clerkships: an interdisciplinary
      approach.
AB  - The Collaborative Curriculum Project (CCP) is one of three components of the
      Family Medicine Curriculum Resource Project (FMCRP), a federally funded effort to
      provide resources for medical education curricula at the beginning of the 21st
      century. Medical educators and staff from public and private geographically
      distributed medical schools and national specialty organizations in family
      medicine, internal medicine, and pediatrics developed by consensus essential
      clinical competencies that all students should have by the beginning of the
      traditional clerkship year. These competencies are behaviorally measurable and
      organized into the domains used for the Accreditation Council for Graduate
      Medical Education (ACGME) core competencies. Exemplary teaching, assessment, and
      faculty development resources are cited, and attention is given to budgetary
      considerations, application to diverse populations and settings, and
      opportunities for integration within existing courses. The CCP also developed a
      subset of competencies meriting higher priority than currently provided in the
      pre-clerkship years. These priority areas were empirically validated through a
      national survey of clerkship directors in six disciplines. The project's
      documents are not intended to prescribe curricula for any school but rather to
      provide curricular decision makers with suggestions regarding priorities for
      allocation of time and resources and detailed clinical competency statements and
      other resources useful for faculty developing clinical courses in the first 2
      years of medical school.

PMID- 17186446
TI  - Family medicine clerkship curriculum: competencies and resources.
AB  - Funded by the Health Resources and Services Administration (HRSA) from 2000-2005,
      the Family Medicine Curriculum Resource Project (FMCRP) developed a set of
      resources to improve medical student education. As part of this project, the
      FMCRP Clerkship Workgroup created and organized resources for developing,
      teaching, and evaluating a family medicine clerkship. Using the Accreditation
      Council for Graduate Medical Education competencies as the overarching structure,
      the organizational scheme incorporated family medicine principles and themes in
      covering core topics. This curricular resource was designed to be flexible and
      adaptable to different medical schools and curricular settings.

PMID- 17186448
TI  - The Family Medicine Curriculum Resource Project: implications for faculty
      development.
AB  - Faculty development implications related to implementing the Family Medicine
      Curriculum Resource (FMCR) Project provide an opportunity to look at the
      recommendations of the Society of Teachers of Family Medicine's federally funded
      Faculty Futures Initiative (FFI) and the recent Future of Family Medicine (FFM)
      project. Implications for faculty development include the importance of the
      clerkship setting, originally defined in 1991, with new features added in today's
      practice environment as outlined by the FFM and the changing assumptions in
      approaching faculty development. Previously, faculty development focused on
      teaching learners to master current knowledge. Now, faculty must teach learners
      how to master new competencies throughout their lives; learners need to learn how
      they and others learn now. Teaching must focus on how to learn in the future as
      well as what to learn for the present. Competence ("what individuals know or are
      able to do in terms of knowledge, skills, and attitudes") has become the focus of
      curriculum development efforts over the last few years and most appropriately
      serves as the focus of curriculum development in the FMCR Project. Implications
      for developing teachers and preceptors focus on the skills and circumstances
      required to teach and evaluate all types (cognitive, metacognitive, and
      affective) of competence. In the new culture, novel teaching methods will serve
      as the focus of faculty development in teaching and of educational ("best
      practices") research.

PMID- 17186447
TI  - A proposal to address the curriculum for the M-4 medical student.
AB  - The unstructured and elective nature of the fourth-year medical student (M4)
      medical school curriculum has been recognized by medical educators as an area of
      concern. Few accepted guidelines exist for the M4 curriculum, and students
      exercise significant discretion over their experience. The Family Medicine
      Curriculum Resource Project post-clerkship resource was developed by the Society
      of Teachers of Family Medicine under contract from the Health Resources and
      Service Agency to support medical educators in the development of curricula and
      assessment of student needs for the M4 year of medical school. The post-clerkship
      resource defines competencies for graduation and contains educational resources
      as well as recommendations for faculty development and student evaluation in the
      M4 year.

PMID- 17186449
TI  - Family Medicine Curriculum Resource Project: the future.
AB  - Under contract to the Health Resources and Services Administration (HRSA), the
      Society of Teachers of Family Medicine (STFM) created an undergraduate medical
      education curricular resource designed to train physicians to practice in the
      21st century. An interdisciplinary group of more than 35 educators worked for 4
      years to create the Family Medicine Curriculum Resource (FMCR). By consensus, the
      Accreditation Council for Graduate Medical Education (ACGME) competencies were
      adopted as the theoretical framework for this project. The FMCR provides
      materials for the preclerkship years, the third-year family medicine clerkship,
      the postclerkship year, and faculty development, as well as guidance for
      integrating topics of special interest to the federal government (such as,
      geriatrics, Healthy People 2010, genetics, informatics) into a 4-year continuum
      of medical education. There are challenges inherent in implementing each
      component of the FMCR. For example, can the ACGME competency-based approach be
      adapted to undergraduate medical education? Can the densely packed preclerkship
      years be adapted to include more focused effort on developing these competencies,
      and whose job is it anyway? What is "core" to being a competent clinician, and
      what information can be obtained when needed from medical informatics sources?
      Will family medicine educators embrace the FMCR recommendations for their third
      year clerkships? Will exit assessment of the competency levels of graduating
      medical students be achieved, and can it make them more capable residents? Can
      faculty in different clinical and educational settings integrate the teaching of
      "how to learn" into their repertoire? How will faculty development innovation
      progress in a time of increasing emphasis on clinical productivity? Developing a
      common language and adoption of core competencies for all levels of medical
      education is imperative in a society that is focusing on improving health care
      quality and outcomes. The FMCR Project has developed a curricular resource to
      assist medical educators in this task. The challenge for the future is to measure
      how the FMCR is used and to ascertain if it has an influence on better patient
      and system outcomes.

PMID- 17186450
TI  - Family medicine predoctoral education: 30-something.

PMID- 17186452
TI  - Thailand: diagnosing and treating psychological problems in limited resource
      settings.

PMID- 17186453
TI  - Scotland: easy access versus continuity-what is important to patients and
      doctors?

PMID- 17186454
TI  - Canada: how to improve your clinical prevention activities.

PMID- 17186455
TI  - Treatment adherence in schizophrenia. Spanish clinical consensus.
AB  - Objective. Establish a Spanish Consensus on Therapeutic Compliance in
      Schizophrenia.<p> Material and methods. An experts committee designed a specific
      questionnaire having 40 questions and 293 options. The questions referred to the
      definition and general assessment of compliance in schizophrenia, factors
      involved, intervention strategies in outpatients and in acute units and
      management of oral and long duration injectable antipsychotic drugs and other non
      pharmacological therapies. First, second or third line strategy values of choice
      were assigned according to the answers obtained for each item. The questionnaire
      was sent to 383 psychiatrists of a Therapeutic Compliance Work Group. A total of
      326 answers were received with an electronic system that guaranteed their
      confidentiality.</p><p> Results and conclusions. There is maximum agreement on
      considering the seriousness of the compliance problem, its repercussion in
      relapses, the patient's course and increase in health care costs. The strategies
      preferred to evaluate compliance are: counting of the injectable drug
      administration and determination of plasma concentrations. The Consensus
      considers that specific intervention is necessary when the patient has already
      suffered several relapses due to low therapeutic compliance, when null awareness
      of disease is detected or if there is comorbidity with toxic consumption.
      Psychoeducational is the non-pharmacological strategy having the greatest
      consensus grade if intervention is needed. Treatments with atypical injectable,
      long duration, antipsychotic drugs obtain the best grade in accordance with
      pharmacological strategies of first choice, in different clinical situations to
      avoid or improve therapeutic adherence.</p><p> Key words:<br /> Adherence.
      Compliance. Schizophrenia. Consensus.</p>

PMID- 17186457
TI  - Results of the questions.

PMID- 17186456
TI  - Consensus summary.

PMID- 17186459
TI  - Powerful multilocus tests of genetic association in the presence of gene-gene and
      gene-environment interactions.
AB  - In modern genetic epidemiology studies, the association between the disease and a
      genomic region, such as a candidate gene, is often investigated using multiple
      SNPs. We propose a multilocus test of genetic association that can account for
      genetic effects that might be modified by variants in other genes or by
      environmental factors. We consider use of the venerable and parsimonious Tukey's
      1-degree-of-freedom model of interaction, which is natural when individual SNPs
      within a gene are associated with disease through a common biological mechanism;
      in contrast, many standard regression models are designed as if each SNP has
      unique functional significance. On the basis of Tukey's model, we propose a novel
      but computationally simple generalized test of association that can
      simultaneously capture both the main effects of the variants within a genomic
      region and their interactions with the variants in another region or with an
      environmental exposure. We compared performance of our method with that of two
      standard tests of association, one ignoring gene-gene/gene-environment
      interactions and the other based on a saturated model of interactions. We
      demonstrate major power advantages of our method both in analysis of data from a
      case-control study of the association between colorectal adenoma and DNA variants
      in the NAT2 genomic region, which are well known to be related to a common
      biological phenotype, and under different models of gene-gene interactions with
      use of simulated data.

PMID- 17186458
TI  - A common haplotype of the glucokinase gene alters fasting glucose and birth
      weight: association in six studies and population-genetics analyses.
AB  - Fasting glucose is associated with future risk of type 2 diabetes and ischemic
      heart disease and is tightly regulated despite considerable variation in
      quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose
      concentration is an important determinant of offspring birth weight. The key
      determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of
      GCK cause fasting hyperglycemia and alter birth weight. The extent to which
      common variation of GCK explains normal variation of fasting glucose and birth
      weight is not known. We aimed to comprehensively define the role of variation of
      GCK in determination of fasting glucose and birth weight, using a tagging SNP
      (tSNP) approach and studying 19,806 subjects from six population-based studies.
      Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting
      glucose at all ages in the normal population and exceeded genomewide levels of
      significance (P=10-9). rs3757840 was also highly significantly associated with
      fasting glucose (P=8x10-7), but haplotype analysis revealed that this is
      explained by linkage disequilibrium (r2=0.2) with rs1799884. A maternal A allele
      at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g)
      increase in offspring birth weight (P=.002). Genetic variation influencing birth
      weight may have conferred a selective advantage in human populations. We
      performed extensive population-genetics analyses to look for evidence of recent
      positive natural selection on patterns of GCK variation. However, we found no
      strong signature of positive selection. In conclusion, a comprehensive analysis
      of common variation of the glucokinase gene shows that this is the first gene to
      be reproducibly associated with fasting glucose and fetal growth.

PMID- 17186460
TI  - Biochemical and genetic analysis of ANK in arthritis and bone disease.
AB  - Mutations in the progressive ankylosis gene (Ank/ANKH) cause surprisingly
      different skeletal phenotypes in mice and humans. In mice, recessive loss-of
      function mutations cause arthritis, ectopic crystal formation, and joint fusion
      throughout the body. In humans, some dominant mutations cause chondrocalcinosis,
      an adult-onset disease characterized by the deposition of ectopic joint crystals.
      Other dominant mutations cause craniometaphyseal dysplasia, a childhood disease
      characterized by sclerosis of the skull and abnormal modeling of the long bones,
      with little or no joint pathology. Ank encodes a multiple-pass transmembrane
      protein that regulates pyrophosphate levels inside and outside tissue culture
      cells in vitro, but its mechanism of action is not yet clear, and conflicting
      models have been proposed to explain the effects of the human mutations. Here, we
      test wild-type and mutant forms of ANK for radiolabeled pyrophosphate-transport
      activity in frog oocytes. We also reconstruct two human mutations in a bacterial
      artificial chromosome and test them in transgenic mice for rescue of the Ank null
      phenotype and for induction of new skeletal phenotypes. Wild-type ANK stimulates
      saturable transport of pyrophosphate ions across the plasma membrane, with half
      maximal rates attained at physiological levels of pyrophosphate.
      Chondrocalcinosis mutations retain apparently wild-type transport activity and
      can rescue the joint-fusion phenotype of Ank null mice. Craniometaphyseal
      dysplasia mutations do not transport pyrophosphate and cannot rescue the defects
      of Ank null mice. Furthermore, microcomputed tomography revealed previously
      unappreciated phenotypes in Ank null mice that are reminiscent of
      craniometaphyseal dysplasia. The combination of biochemical and genetic analyses
      presented here provides insight into how mutations in ANKH cause human skeletal
      disease.

PMID- 17186461
TI  - Mutations of presenilin genes in dilated cardiomyopathy and heart failure.
AB  - Two common disorders of the elderly are heart failure and Alzheimer disease (AD).
      Heart failure usually results from dilated cardiomyopathy (DCM). DCM of unknown
      cause in families has recently been shown to result from genetic disease,
      highlighting newly discovered disease mechanisms. AD is the most frequent
      neurodegenerative disease of older Americans. Familial AD is caused most commonly
      by presenilin 1 (PSEN1) or presenilin 2 (PSEN2) mutations, a discovery that has
      greatly advanced the field. The presenilins are also expressed in the heart and
      are critical to cardiac development. We hypothesized that mutations in
      presenilins may also be associated with DCM and that their discovery could
      provide new insight into the pathogenesis of DCM and heart failure. A total of
      315 index patients with DCM were evaluated for sequence variation in PSEN1 and
      PSEN2. Families positive for mutations underwent additional clinical, genetic,
      and functional studies. A novel PSEN1 missense mutation (Asp333Gly) was
      identified in one family, and a single PSEN2 missense mutation (Ser130Leu) was
      found in two other families. Both mutations segregated with DCM and heart
      failure. The PSEN1 mutation was associated with complete penetrance and
      progressive disease that resulted in the necessity of cardiac transplantation or
      in death. The PSEN2 mutation showed partial penetrance, milder disease, and a
      more favorable prognosis. Calcium signaling was altered in cultured skin
      fibroblasts from PSEN1 and PSEN2 mutation carriers. These data indicate that
      PSEN1 and PSEN2 mutations are associated with DCM and heart failure and implicate
      novel mechanisms of myocardial disease.

PMID- 17186462
TI  - Tricellulin is a tight-junction protein necessary for hearing.
AB  - The inner ear has fluid-filled compartments of different ionic compositions,
      including the endolymphatic and perilymphatic spaces of the organ of Corti; the
      separation from one another by epithelial barriers is required for normal
      hearing. TRIC encodes tricellulin, a recently discovered tight-junction (TJ)
      protein that contributes to the structure and function of tricellular contacts of
      neighboring cells in many epithelial tissues. We show that, in humans, four
      different recessive mutations of TRIC cause nonsyndromic deafness (DFNB49), a
      surprisingly limited phenotype, given the widespread tissue distribution of
      tricellulin in epithelial cells. In the inner ear, tricellulin is concentrated at
      the tricellular TJs in cochlear and vestibular epithelia, including the
      structurally complex and extensive junctions between supporting and hair cells.
      We also demonstrate that there are multiple alternatively spliced isoforms of
      TRIC in various tissues and that mutations of TRIC associated with hearing loss
      remove all or most of a conserved region in the cytosolic domain that binds to
      the cytosolic scaffolding protein ZO-1. A wild-type isoform of tricellulin, which
      lacks this conserved region, is unaffected by the mutant alleles and is
      hypothesized to be sufficient for structural and functional integrity of
      epithelial barriers outside the inner ear.

PMID- 17186463
TI  - HLA and genomewide allele sharing in dizygotic twins.
AB  - Gametic selection during fertilization or the effects of specific genotypes on
      the viability of embryos may cause a skewed transmission of chromosomes to
      surviving offspring. A recent analysis of transmission distortion in humans
      reported significant excess sharing among full siblings. Dizygotic (DZ) twin
      pairs are a special case of the simultaneous survival of two genotypes, and there
      have been reports of DZ pairs with excess allele sharing around the HLA locus, a
      candidate locus for embryo survival. We performed an allele-sharing study of
      1,592 DZ twin pairs from two independent Australian cohorts, of which 1,561 pairs
      were informative for linkage on chromosome 6. We also analyzed allele sharing in
      336 DZ twin pairs from The Netherlands. We found no evidence of excess allele
      sharing, either at the HLA locus or in the rest of the genome. In contrast, we
      found evidence of a small but significant (P=.003 for the Australian sample)
      genomewide deficit in the proportion of two alleles shared identical by descent
      among DZ twin pairs. We reconciled conflicting evidence in the literature for
      excess genomewide allele sharing by performing a simulation study that shows how
      undetected genotyping errors can lead to an apparent deficit or excess of allele
      sharing among sibling pairs, dependent on whether parental genotypes are known.
      Our results imply that gene-mapping studies based on affected sibling pairs that
      include DZ pairs will not suffer from false-positive results due to loci involved
      in embryo survival.

PMID- 17186465
TI  - Exact tests of Hardy-Weinberg equilibrium and homogeneity of disequilibrium
      across strata.
AB  - Detecting departures from Hardy-Weinberg equilibrium (HWE) of marker-genotype
      frequencies is a crucial first step in almost all human genetic analyses. When a
      sample is stratified by multiple ethnic groups, it is important to allow the
      marker-allele frequencies to differ over the strata. In this situation, it is
      common to test for HWE by using an exact test within each stratum and then using
      the minimum P value as a global test. This approach does not account for multiple
      testing, and, because it does not combine information over strata, it does not
      have optimal power. Several approximate methods to combine information over
      strata have been proposed, but most of them sum over strata a measure of
      departure from HWE; if the departures are in different directions, then summing
      can diminish the overall evidence of departure from HWE. An exact stratified test
      is more appealing because it uses the probability of genotype configurations
      across the strata as evidence for global departures from HWE. We developed an
      exact stratified test for HWE for diallelic markers, such as single-nucleotide
      polymorphisms (SNPs), and an exact test for homogeneity of Hardy-Weinberg
      disequilibrium. By applying our methods to data from Perlegen and HapMap--a
      combined total of more than five million SNP genotypes, with three to four strata
      and strata sizes ranging from 23 to 60 subjects--we illustrate that the exact
      stratified test provides more-robust and more-powerful results than those
      obtained by either the minimum of exact test P values over strata or approximate
      stratified tests that sum measures of departure from HWE. Hence, our new methods
      should be useful for samples composed of multiple ethnic groups.

PMID- 17186464
TI  - Premature truncation of a novel protein, RD3, exhibiting subnuclear localization
      is associated with retinal degeneration.
AB  - The rd3 mouse is one of the oldest identified models of early-onset retinal
      degeneration. Using the positional candidate approach, we have identified a C-->T
      substitution in a novel gene, Rd3, that encodes an evolutionarily conserved
      protein of 195 amino acids. The rd3 mutation results in a predicted stop codon
      after residue 106. This change is observed in four rd3 lines derived from the
      original collected mice but not in the nine wild-type mouse strains that were
      examined. Rd3 is preferentially expressed in the retina and exhibits increasing
      expression through early postnatal development. In transiently transfected COS-1
      cells, the RD3-fusion protein shows subnuclear localization adjacent to
      promyelocytic leukemia-gene-product bodies. The truncated mutant RD3 protein is
      detectable in COS-1 cells but appears to get degraded rapidly. To explore
      potential association of the human RD3 gene at chromosome 1q32 with
      retinopathies, we performed a mutation screen of 881 probands from North America,
      India, and Europe. In addition to several alterations of uncertain significance,
      we identified a homozygous alteration in the invariant G nucleotide of the RD3
      exon 2 donor splice site in two siblings with Leber congenital amaurosis. This
      mutation is predicted to result in premature truncation of the RD3 protein,
      segregates with the disease, and is not detected in 121 ethnically matched
      control individuals. We suggest that the retinopathy-associated RD3 protein is
      part of subnuclear protein complexes involved in diverse processes, such as
      transcription and splicing.

PMID- 17186467
TI  - Human adaptive evolution at Myostatin (GDF8), a regulator of muscle growth.
AB  - Myostatin (GDF8) is a negative regulator of muscle growth in mammals, and loss-of
      function mutations are associated with increased skeletal-muscle mass in mice,
      cattle, and humans. Here, we show that positive natural selection has acted on
      human nucleotide variation at GDF8, since the observed ratio of
      nonsynonymous:synonymous changes among humans is significantly greater than
      expected under the neutral model and is strikingly different from patterns
      observed across mammalian orders. Furthermore, extended haplotypes around GDF8
      suggest that two amino acid variants have been subject to recent positive
      selection. Both mutations are rare among non-Africans yet are at frequencies of
      up to 31% in sub-Saharan Africans. These signatures of selection at the molecular
      level suggest that human variation at GDF8 is associated with functional
      differences.

PMID- 17186466
TI  - Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically
      heterogeneous heart-muscle disorder characterized by progressive fibrofatty
      replacement of right ventricular myocardium and an increased risk of sudden
      cardiac death. Mutations in desmosomal proteins that cause ARVC have been
      previously described; therefore, we investigated 88 unrelated patients with the
      disorder for mutations in human desmosomal cadherin desmocollin-2 (DSC2). We
      identified a heterozygous splice-acceptor-site mutation in intron 5 (c.631-2A-
      >G) of the DSC2 gene, which led to the use of a cryptic splice-acceptor site and
      the creation of a downstream premature termination codon. Quantitative analysis
      of cardiac DSC2 expression in patient specimens revealed a marked reduction in
      the abundance of the mutant transcript. Morpholino knockdown in zebrafish embryos
      revealed a requirement for dsc2 in the establishment of the normal myocardial
      structure and function, with reduced desmosomal plaque area, loss of the
      desmosome extracellular electron-dense midlines, and associated myocardial
      contractility defects. These data identify DSC2 mutations as a cause of ARVC in
      humans and demonstrate that physiologic levels of DSC2 are crucial for normal
      cardiac desmosome formation, early cardiac morphogenesis, and cardiac function.

PMID- 17186468
TI  - Increased activity of coagulation factor XII (Hageman factor) causes hereditary
      angioedema type III.
AB  - Hereditary angioedema (HAE) is characterized clinically by recurrent acute skin
      swelling, abdominal pain, and potentially life-threatening laryngeal edema. Three
      forms of HAE have been described. The classic forms, HAE types I and II, occur as
      a consequence of mutations in the C1-inhibitor gene. In contrast to HAE types I
      and II, HAE type III has been observed exclusively in women, where it appears to
      be correlated with conditions of high estrogen levels--for example, pregnancy or
      the use of oral contraceptives. A recent report proposed two missense mutations
      (c.1032C-->A and c.1032C-->G) in F12, the gene encoding human coagulation factor
      XII (FXII, or Hageman factor) as a possible cause of HAE type III. Here, we
      report the occurrence of the c.1032C-->A (p.Thr328Lys) mutation in an HAE type
      III-affected family of French origin. Investigation of the F12 gene in a large
      German family did not reveal a coding mutation. Haplotype analysis with use of
      microsatellite markers is compatible with locus heterogeneity in HAE type III. To
      shed more light on the pathogenic relevance of the HAE type III-associated
      p.Thr328Lys mutation, we compared FXII activity and plasma levels in patients
      carrying the mutation with that of healthy control individuals. Our data strongly
      suggest that p.Thr328Lys is a gain-of-function mutation that markedly increases
      FXII amidolytic activity but that does not alter FXII plasma levels. We conclude
      that enhanced FXII enzymatic plasma activity in female mutation carriers leads to
      enhanced kinin production, which results in angioedema. Transcription of F12 is
      positively regulated by estrogens, which may explain why only women are affected
      with HAE type III. The results of our study represent an important step toward an
      understanding of the molecular processes involved in HAE type III and provide
      diagnostic and possibly new therapeutic opportunities.

PMID- 17186469
TI  - Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4)
      cause autosomal recessive anonychia.
AB  - Anonychia is an autosomal recessive disorder characterized by the congenital
      absence of finger- and toenails. In a large German nonconsanguineous family with
      four affected and five unaffected siblings with isolated total congenital
      anonychia, we performed genomewide mapping and showed linkage to 20p13. Analysis
      of the RSPO4 gene within this interval revealed a frameshift and a
      nonconservative missense mutation in exon 2 affecting the highly conserved first
      furin-like cysteine-rich domain. Both mutations were not present among controls
      and were shown to segregate with the disease phenotype. RSPO4 is a member of the
      recently described R-spondin family of secreted proteins that play a major role
      in activating the Wnt/ beta -catenin signaling pathway. Wnt signaling is
      evolutionarily conserved and plays a pivotal role in embryonic development,
      growth regulation of multiple tissues, and cancer development. Our findings add
      to the increasing body of evidence indicating that mesenchymal-epithelial
      interactions are crucial in nail development and put anonychia on the growing
      list of congenital malformation syndromes caused by Wnt-signaling-pathway
      defects. To the best of our knowledge, this is the first gene known to be
      responsible for an isolated, nonsyndromic nail disorder.

PMID- 17186470
TI  - Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized
      by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is
      associated with heterozygous mutations in the ribosomal protein (RP) S19 gene
      (RPS19) in approximately 25% of probands. We report identification of de novo
      nonsense and splice-site mutations in another RP, RPS24 (encoded by RPS24 [10q22
      q23]) in approximately 2% of RPS19 mutation-negative probands. This finding
      strongly suggests that DBA is a disorder of ribosome synthesis and that mutations
      in other RP or associated genes that lead to disrupted ribosomal biogenesis
      and/or function may also cause DBA.

PMID- 17186471
TI  - Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1
      complex, AP1S2, cause X-linked mental retardation.
AB  - In a systematic sequencing screen of the coding exons of the X chromosome in 250
      families with X-linked mental retardation (XLMR), we identified two nonsense
      mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in
      three families. Affected individuals in these families showed mild-to-profound
      mental retardation. Other features included hypotonia early in life and delay in
      walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor
      protein complex found at the cytoplasmic face of coated vesicles located at the
      Golgi complex. The complex mediates the recruitment of clathrin to the vesicle
      membrane. Aberrant endocytic processing through disruption of adaptor protein
      complexes is likely to result from the AP1S2 mutations identified in the three
      XLMR-affected families, and such defects may plausibly cause abnormal synaptic
      development and function. AP1S2 is the first reported XLMR gene that encodes a
      protein directly involved in the assembly of endocytic vesicles.

PMID- 17186473
TI  - Genetic heterogeneity in Italian families with IgA nephropathy: suggestive
      linkage for two novel IgA nephropathy loci.
AB  - IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, but its
      etiologic mechanisms are still poorly understood. Different prevalences among
      ethnic groups and familial aggregation, together with an increased familial risk,
      suggest important genetic influences on its pathogenesis. A locus for familial
      IgAN, called "IGAN1," on chromosome 6q22-23 has been described, without the
      identification of any responsible gene. The partners of the European IgAN
      Consortium organized a second genomewide scan in 22 new informative Italian
      multiplex families. A total of 186 subjects (59 affected and 127 unaffected) were
      genotyped and were included in a two-stage genomewide linkage analysis. The
      regions 4q26-31 and 17q12-22 exhibited the strongest evidence of linkage by
      nonparametric analysis (best P=.0025 and .0045, respectively). These
      localizations were also supported by multipoint parametric analysis, in which
      peak LOD scores of 1.83 ( alpha =0.50) and 2.56 ( alpha =0.65) were obtained
      using the affected-only dominant model, and by allowance for the presence of
      genetic heterogeneity. Our results provide further evidence for genetic
      heterogeneity among families with IgAN. Evidence of linkage to multiple
      chromosomal regions is consistent with both an oligo/polygenic and a multiple
      susceptibility-gene model for familial IgAN, with small or moderate effects in
      determining the pathological phenotype. Although we identified new candidate
      regions, replication studies are required to confirm the genetic contribution to
      familial IgAN.

PMID- 17186472
TI  - Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl
      diphosphate synthase subunit 2 (PDSS2) mutations.
AB  - Coenzyme Q(10) (CoQ(10)) is a vital lipophilic molecule that transfers electrons
      from mitochondrial respiratory chain complexes I and II to complex III.
      Deficiency of CoQ(10) has been associated with diverse clinical phenotypes, but,
      in most patients, the molecular cause is unknown. The first defect in a CoQ(10)
      biosynthetic gene, COQ2, was identified in a child with encephalomyopathy and
      nephrotic syndrome and in a younger sibling with only nephropathy. Here, we
      describe an infant with severe Leigh syndrome, nephrotic syndrome, and CoQ(10)
      deficiency in muscle and fibroblasts and compound heterozygous mutations in the
      PDSS2 gene, which encodes a subunit of decaprenyl diphosphate synthase, the first
      enzyme of the CoQ(10) biosynthetic pathway. Biochemical assays with radiolabeled
      substrates indicated a severe defect in decaprenyl diphosphate synthase in the
      patient's fibroblasts. This is the first description of pathogenic mutations in
      PDSS2 and confirms the molecular and clinical heterogeneity of primary CoQ(10)
      deficiency.

PMID- 17186474
TI  - Elucidating the mechanism for the reduction of nitrite by copper nitrite
      reductase--a contribution from quantum chemical studies.
AB  - Density functional methods have been applied to investigate the properties of the
      active site of copper-containing nitrite reductases and possible reaction
      mechanisms for the enzyme catalysis. The results for a model of the active site
      indicate that a hydroxyl intermediate is not formed during the catalytic cycle,
      but rather a state with a protonated nitrite bound to the reduced copper.
      Electron affinity calculations indicate that reduction of the T2 copper site does
      not occur immediately after nitrite binding. Proton affinity calculations are
      indicative of substantial pK(a) differences between different states of the T2
      site. The calculations further suggest that the reaction does not proceed until
      uptake of a second proton from the bulk solution. They also indicate that Asp-92
      may play both a key role as a proton donor to the substrate, and a structural
      role in promoting catalysis. In the D92N mutant another base, presumably a nearby
      histidine (His-249) may take the role as the proton donor. On the basis of these
      model calculations and available experimental evidence, an ordered reaction
      mechanism for the reduction of nitrite is suggested. An investigation of the
      binding modes of the nitric oxide product and the nitrite substrate to the model
      site has also been made, indicating that nitric oxide prefers to bind in an end
      on fashion to the reduced T2 site.

PMID- 17186475
TI  - Direct evaluation via forced oscillation method of the electronic state density
      of sizable clusters.
AB  - Metal clusters described in the framework of a simple tight binding model have
      been studied. Application of a dynamical approach (FOM), jointly with efficient
      storage of the sparse Hamiltonian matrix involved, is shown to allow direct
      evaluation of the electronic state density of sizable cubic-symmetry aggregates.

PMID- 17186476
TI  - Comparison of basis set effects and the performance of ab initio and DFT methods
      for probing equilibrium fluctuations.
AB  - The electronic absorption and emission spectra of large molecules reflect the
      extent and timescale of electron-vibration coupling and therefore the extent and
      timescale of relaxation/reorganization in response to a perturbation. In this
      paper, we present a comparison of the calculated absorption and emission spectra
      of NADH in liver alcohol dehydrogenase (LADH), using quantum mechanical/molecular
      mechanical methods, in which we vary the QM component. Specifically, we have
      looked at the influence of basis set (STO-3G, 3-21G*, 6-31G*, CC-pVDZ, and 6
      311G**), as well as the influence of applying the DFT TD-B3LYP and ab initio TD
      HF and CIS methods to the calculation of absorption/emission spectra and the
      reorganization energy (Stokes shift). The ab initio TD-HF and CIS methods
      reproduce the experimentally determined Stokes shift and spectral profiles to a
      high level of agreement, while the TD-B3LYP method significantly underestimates
      the Stokes shift, by 45%. We comment on the origin of this problem and suggest
      that ab initio methods may be naturally more suited to predicting molecular
      behavior away from equilibrium geometries.

PMID- 17186478
TI  - Similarity of RNA secondary structures.
AB  - In this article, we propose a relatively similar measure to compare RNA secondary
      structures. We first transform an RNA secondary structure into a special sequence
      representation. Then, on the basis of symbolic sequence complexity, we obtain the
      relative distance of RNA secondary structures. The examination of
      similarities/dissimilarities of a set of RNA secondary structures at the 3'
      terminus of different viruses illustrates the utility of the approach.

PMID- 17186479
TI  - Convergence of third order correlation energy in atoms and molecules.
AB  - We have investigated the convergence of third order correlation energy within the
      hierarchies of correlation consistent basis sets for helium, neon, and water, and
      for three stationary points of hydrogen peroxide. This analysis confirms that
      singlet pair energies converge much slower than triplet pair energies. In
      addition, singlet pair energies with (aug)-cc-pVDZ and (aug)-cc-pVTZ basis sets
      do not follow a converging trend and energies with three basis sets larger than
      aug-cc-pVTZ are generally required for reliable extrapolations of third order
      correlation energies, making so the explicitly correlated R12 calculations
      preferable.

PMID- 17186480
TI  - On the quality of the hardness kernel and the Fukui function to evaluate the
      global hardness.
AB  - An approximated hardness kernel, which includes the second derivative with
      respect to the density of the kinetic energy, the electron-electron coulomb
      repulsion, and the exchange density functionals, has been tested for the
      calculation of the global hardness. The results obtained for a series of 40
      cations and neutral systems and 16 anions represent in most cases an improvement
      of the results obtained using the HOMO-LUMO gap approach and indicate the
      viability of this approach to evaluate global hardness. In addition, the
      relevance of the Fukui function approximation and the role of the three
      components of the hardness kernel in the evaluation of the global hardness have
      been analyzed.

PMID- 17186477
TI  - CHARMM force field parameters for simulation of reactive intermediates in native
      and thio-substituted ribozymes.
AB  - Force field parameters specifically optimized for residues important in the study
      of RNA catalysis are derived from density-functional calculations, in a fashion
      consistent with the CHARMM27 all-atom empirical force field. Parameters are
      presented for residues that model reactive RNA intermediates and transition state
      analogs, thio-substituted phosphates and phosphoranes, and bound Mg(2+) and di
      metal bridge complexes. Target data was generated via density-functional
      calculations at the B3LYP/6-311++G(3df,2p)// B3LYP/6-31++G(d,p) level. Partial
      atomic charges were initially derived from CHelpG electrostatic potential fitting
      and subsequently adjusted to be consistent with the CHARMM27 charges. Lennard
      Jones parameters were determined to reproduce interaction energies with water
      molecules. Bond, angle, and torsion parameters were derived from the density
      functional calculations and renormalized to maintain compatibility with the
      existing CHARMM27 parameters for standard residues. The extension of the CHARMM27
      force field parameters for the nonstandard biological residues presented here
      will have considerable use in simulations of ribozymes, including the study of
      freeze-trapped catalytic intermediates, metal ion binding and occupation, and
      thio effects.

PMID- 17186481
TI  - A theoretical study of fullerene-ferrocene hybrids.
AB  - Using density functional theory within the generalized gradient approximation, I
      analyzed the electronic structure of a C(60)-ferrocene hybrid [= C(60) (*) FeCp]
      around HOMO in comparison with that of ferrocene, where C(60) (*) and Cp denote
      C(60)(CH(3))(5) and a cyclopentadienyl ring. HOMO-LUMO gap is significantly
      smaller than that of ferrocene because of the intervention of pi(C(60) (*))
      states below LUMO. In addition, geometrical and electronic structures of N@C(60)
      (*) FeCp are also investigated. I find that there are two isomers with the energy
      difference of 0.13 eV. In one of the two, the encased nitrogen atom is located at
      the center of the fullerene cage. The Fe atom is eta(5)-coordinated to both Cp
      and R*, where R* is a five-membered ring of C(60) (*) cage. On the other hand,
      the atom is coordinated to R* with eta(4)-hapticity, and the nitrogen atom is
      bonded to a carbon atom of the R* ring in the other isomer. Upon the
      isomerization between the two isomers, there occurs a partial transfer of spin
      density between the nitrogen and Fe atoms as well as the creation and breaking of
      a C-N bond.

PMID- 17186482
TI  - Gradient tabu search.
AB  - This paper presents a modification of the tabu search called gradient tabu search
      (GTS). It uses analytical gradients for a fast minimization to the next local
      minimum and analytical diagonal elements of the Hessian to escape local minima.
      For an efficient blocking of already visited areas tabu regions and tabu
      directions are introduced into the tabu list (TL). Trials with various well-known
      test functions indicate that the GTS is a very promising approach to determine
      local and global minima of differentiable functions. Possible application areas
      could be optimization routines for force field parameters or conformational
      searches for large molecules.

PMID- 17186483
TI  - SODOCK: swarm optimization for highly flexible protein-ligand docking.
AB  - Protein-ligand docking can be formulated as a parameter optimization problem
      associated with an accurate scoring function, which aims to identify the
      translation, orientation, and conformation of a docked ligand with the lowest
      energy. The parameter optimization problem for highly flexible ligands with many
      rotatable bonds is more difficult than that for less flexible ligands using
      genetic algorithm (GA)-based approaches, due to the large numbers of parameters
      and high correlations among these parameters. This investigation presents a novel
      optimization algorithm SODOCK based on particle swarm optimization (PSO) for
      solving flexible protein-ligand docking problems. To improve efficiency and
      robustness of PSO, an efficient local search strategy is incorporated into
      SODOCK. The implementation of SODOCK adopts the environment and energy function
      of AutoDock 3.05. Computer simulation results reveal that SODOCK is superior to
      the Lamarckian genetic algorithm (LGA) of AutoDock, in terms of convergence
      performance, robustness, and obtained energy, especially for highly flexible
      ligands. The results also reveal that PSO is more suitable than the conventional
      GA in dealing with flexible docking problems with high correlations among
      parameters. This investigation also compared SODOCK with four state-of-the-art
      docking methods, namely GOLD 1.2, DOCK 4.0, FlexX 1.8, and LGA of AutoDock 3.05.
      SODOCK obtained the smallest RMSD in 19 of 37 cases. The average 2.29 A of the 37
      RMSD values of SODOCK was better than those of other docking programs, which were
      all above 3.0 A.

PMID- 17186484
TI  - Ab initio quantum mechanics-based free energy perturbation method for calculating
      relative solvation free energies.
AB  - A free energy perturbation (FEP) method was developed that uses ab initio quantum
      mechanics (QM) for treating the solute molecules and molecular mechanics (MM) for
      treating the surroundings. Like our earlier results using AM1 semi empirical QMs,
      the ab initio QM/MM-based FEP method was shown to accurately calculate relative
      solvation free energies for a diverse set of small molecules that differ
      significantly in structure, aromaticity, hydrogen bonding potential, and electron
      density. Accuracy was similar to or better than conventional FEP methods. The
      QM/MM-based methods eliminate the need for time-consuming development of MM force
      field parameters, which are frequently required for drug-like molecules
      containing structural motifs not adequately described by MM. Future automation of
      the method and parallelization of the code for Linux 128/256/512 clusters is
      expected to enhance the speed and increase its use for drug design and lead
      optimization.

PMID- 17186485
TI  - Free energy profiles for monomer capture in Grubbs- and SHOP-type olefin
      polymerization catalysts: a constraint ab initio molecular dynamics study.
AB  - Density functional theory together with Car-Parrinello ab initio molecular
      dynamics simulation has been used to investigate the free energy profiles (FEP)
      of monomer capture in Grubbs- and SHOP-type olefin polymerization catalysts. The
      FEPs along the reaction coordinates at 300 K were determined directly by a point
      wise thermodynamic integration technique. Comparison between potential energy
      profile (PEP) and the FEP has been made. The results show that, for both
      catalysts, the PEP for the monomer ethylene uptake by the metal center is a
      typical Morse curve without energy barrier. However, a small barrier (1.8
      kcal/mol for Grubbs catalyst and 2.4 kcal/mol for SHOP catalyst) exists on the
      FEP. The pi complexation energy on the FES at 300 K is higher by 10-12 kcal/mol
      over that on the PES. The differences between FES and PES are due to entropy
      contribution. Slow growth simulations on the ethylene capture process show that
      the ethylene attacks the metal center by an asynchronous mode. This indicates
      that the forming of the pi-bonding between the metal and ethylene is initiated by
      electrophilic attack of the metal to one of the ethylene carbons.

PMID- 17186486
TI  - A theoretical investigation of the excited states of OCLO radical, cation, and
      anion using the CASSCF/CASPT2 method.
AB  - Using the complete active space self-consistent field method with a large atomic
      natural orbital basis set, 10, 13, and 9 electronic states of the OClO radical,
      OClO(+) cation, and OClO(-) anion were calculated, respectively. Taking the
      further correlation effects into account, the second-order perturbation (CASPT2)
      calculations were carried out for the energetic calibration. The photoelectron
      spectroscopy of the OClO radical and OClO(-) anion were extensively studied in
      the both case of the adiabatic and vertical ionization energies. The calculated
      results presented the relatively complete assignment of the photoelectron bands
      of the experiments for OClO and its anion. Furthermore, the Rydberg states of the
      OClO radical were investigated by using multiconfigurational CASPT2 (MS-CASPT2)
      theory under the basis set of large atomic natural orbital functions augmented
      with an adapted 1s1p1d Rydberg functions that have specially been built for this
      study. Sixteen Rydberg states were obtained and the results were consistent with
      the experimental results.

PMID- 17186487
TI  - Blue-shifting hydrogen bond in the benzene-benzene and benzene-naphthalene
      complexes.
AB  - Ab initio complete optimizations at MP2/6-31++G** level have been performed in
      the T-shaped geometry of the benzene-benzene and benzene-naphthalene complexes.
      To check the effect of the basis set superposition error (BSSE), optimizations
      have been done in the BSSE corrected and BSSE uncorrected potential energy
      surfaces. The BSSE effect in the calculation of the Hessian has also been
      evaluated to check its influence in the frequency values. Quantum theory atoms in
      molecules (QTAIM) calculations have also been performed on both dimers.
      Intermolecular energies differ around a 25% when the optimization is performed
      with or without counterpoise corrected gradients. The influence of BSSE is also
      noticeable in the distances. Frequency shifts show big changes because of the
      BSSE. Thus, uncorrected values are up 350% larger than corrected ones. The
      hypotheses given in the literature to explain the origin of the blue-shifting
      hydrogen bond do not seem to give a suitable explanation for all characteristics
      of the behavior found in the studied systems.

PMID- 17186488
TI  - Support vector machine based training of multilayer feedforward neural networks
      as optimized by particle swarm algorithm: application in QSAR studies of
      bioactivity of organic compounds.
AB  - Multilayer feedforward neural networks (MLFNNs) are important modeling techniques
      widely used in QSAR studies for their ability to represent nonlinear
      relationships between descriptors and activity. However, the problems of
      overfitting and premature convergence to local optima still pose great challenges
      in the practice of MLFNNs. To circumvent these problems, a support vector machine
      (SVM) based training algorithm for MLFNNs has been developed with the
      incorporation of particle swarm optimization (PSO). The introduction of the SVM
      based training mechanism imparts the developed algorithm with inherent capacity
      for combating the overfitting problem. Moreover, with the implementation of PSO
      for searching the optimal network weights, the SVM based learning algorithm shows
      relatively high efficiency in converging to the optima. The proposed algorithm
      has been evaluated using the Hansch data set. Application to QSAR studies of the
      activity of COX-2 inhibitors is also demonstrated. The results reveal that this
      technique provides superior performance to backpropagation (BP) and PSO training
      neural networks.

PMID- 17186489
TI  - Density functional theory augmented with an empirical dispersion term.
      Interaction energies and geometries of 80 noncovalent complexes compared with ab
      initio quantum mechanics calculations.
AB  - Standard density functional theory (DFT) is augmented with a damped empirical
      dispersion term. The damping function is optimized on a small, well balanced set
      of 22 van der Waals (vdW) complexes and verified on a validation set of 58 vdW
      complexes. Both sets contain biologically relevant molecules such as nucleic acid
      bases. Results are in remarkable agreement with reference high-level wave
      function data based on the CCSD(T) method. The geometries obtained by full
      gradient optimization are in very good agreement with the best available
      theoretical reference. In terms of the standard deviation and average errors,
      results including the empirical dispersion term are clearly superior to all pure
      density functionals investigated-B-LYP, B3-LYP, PBE, TPSS, TPSSh, and BH-LYP-and
      even surpass the MP2/cc-pVTZ method. The combination of empirical dispersion with
      the TPSS functional performs remarkably well. The most critical part of the
      empirical dispersion approach is the damping function. The damping parameters
      should be optimized for each density functional/basis set combination separately.
      To keep the method simple, we optimized mainly a single factor, s(R), scaling
      globally the vdW radii. For good results, a basis set of at least triple-zeta
      quality is required and diffuse functions are recommended, since the basis set
      superposition error seriously deteriorates the results. On average, the
      dispersion contribution to the interaction energy missing in the DFT functionals
      examined here is about 15 and 100% for the hydrogen-bonded and stacked complexes
      considered, respectively.

PMID- 17186490
TI  - Antibacterial activity of flavonoids and phenylpropanoids from Marrubium globosum
      ssp. libanoticum.
AB  - Marrubium globosum Montbr. et Auch. ex Benth. ssp. libanoticum Boiss. (Lamiaceae)
      is a medicinal plant used for the treatment of inflammatory diseases, asthma,
      coughs and other pulmonary and urinary problems. The goal of our study was to
      assess the biological activity of M. globosum testing the methanol extract of
      aerial parts for its antibacterial activity against bacteria known to cause
      respiratory, gastrointestinal, skin and urinary disorders; the extract showed
      antibacterial effects against all the strains of bacteria used. A purification of
      this active extract showed the presence, as main constituents, of verbascoside,
      isorhamnetin 3-O-beta-D-rutinoside, quercetin 3-O-beta-D-rutinoside, naringenin 7
      O-beta-D-glucoside, kaempferol 3-O-beta-D-rutinoside, isorhamnetin 3-O-beta-D
      glucoside, quercetin 3-O-beta-D-glucoside, apigenin 7-O-(3''-p-coumaryl)
      glucoside, p-methoxy-cinnamic acid, kaempferol 3-O-beta-D-glucoside and apigenin
      7-O-beta-D-glucoside. The pure compounds were tested for their antibacterial
      activity; quercetin 3-O-beta-D-rutinoside, verbascoside and naringenin 7-O-beta-D
      glucoside showed the greatest activity.

PMID- 17186491
TI  - In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and
      their derivatives thymoquinone and thymohydroquinone.
AB  - The aim of this study was to examine in vitro the inhibitory activity exerted by
      the main constituents of essential oil obtained from the aromatic plant Thymus
      vulgaris L. on acetylcholinesterase (AChE). The total essential oil and selected
      compounds, specifically linalool and thymol, carvacrol and their derivatives
      thymoquinone and thymohydroquinone, were tested for AChE inhibition.
      Thymohydroquinone exhibited the strongest AChE inhibitory effect over the range
      of concentrations. The AChE inhibitory potential decreased in the following
      order: thymohydroquinone > carvacrol > thymoquinone > essential oil > thymol >
      linalool. It is interesting that the AChE inhibitory effect exerted by carvacrol
      was 10 times stronger than that exerted by its isomer thymol, although thymol and
      carvacrol have a very similar structure.

PMID- 17186492
TI  - Phytochemical, pharmacological and ethnobotanical studies of Rhazya stricta
      Decne.
AB  - Rhazya stricta Decne. is an important medicinal species that is rich in alkaloids
      containing anticancer alkaloids also. This paper reviews phytochemical,
      pharmacological and ethnobotanical studies of R. stricta. Phytochemical and
      pharmacological aspects of the species have been thoroughly explored. Over 100
      alkaloids have been isolated from R. stricta, but the pharmacological activities
      are known for only a few of these compounds. Very few ethnobotanical studies of
      R. stricta have been done, and there is a particular need for such studies in
      various regions of South Asia and in Middle Eastern countries where the species
      grows. These ethnobotanical studies should investigate herbal recipes of R.
      stricta and their use for curing diseases. The genetic diversity, chemotaxonomy
      and allelopathy of R. stricta have not yet been explored, and these studies are
      recommended, with the ultimate goal of benefiting local communities in regions
      where R. stricta grows. This should be achieved by sharing knowledge and through
      the manufacture of herbal drugs from R. stricta's active chemical constituents,
      while protecting intellectual property rights and following the World Health
      Organization's guidelines for safety and efficacy.

PMID- 17186493
TI  - Kushen flavonoids induce apoptosis in tumor cells by inhibition of NF-kappaB
      activation and multiple receptor tyrosine kinase activities.
AB  - In this report, the mechanism of the antitumor activities of Kushen flavonoids
      (KS-Fs) were explored. KS-Fs and kurarinone (Kur), a single flavonoid compound,
      were able to induce apoptosis of H460 and Eca-109 cells in vitro and H460 cells
      in vivo. The apoptosis inducing effect was enhanced in the presence of Taxol. In
      H460 xenograft mice treated with Kur, down-regulation of Bcl-2 and up-regulation
      of caspase 8 and caspase 3 in tumors were observed by immunohistochemical
      staining. In addition, KS-Fs and Kur were able to inhibit TNFalpha-induced NF
      kappaB activation in 293 cells mediated by the decreased IkappaBalpha
      phosphorylation. Further the effects of KS-Fs and Kur on multiple receptor
      tyrosine kinase activities were explored. In cell-based assays, KS-Fs and Kur
      inhibited the EGF-induced EGF receptor phosphorylation in A431 cells and a
      constitutively activated Her-2 in MDA-MB-453s cells. In enzymatic assays, KS-Fs
      and Kur inhibited KDR, but not PDGF BR activities. In A431 xenograft mice treated
      with Kur, an inhibition of EGF receptor phosphorylation in tumors was observed.
      These results reveal a novel mechanism by which KS-Fs induces apoptosis in tumors
      by acting on multiple cellular targets including the inhibition of NF-kappaB
      activation and multiple receptor tyrosine kinase activities.

PMID- 17186494
TI  - Novel antitumor activities of Kushen flavonoids in vitro and in vivo.
AB  - Kushen (KS), the dried roots of Sophora flavescens Aiton, has a long history of
      use in traditional Chinese medicine to treat inflammatory diseases and cancer.
      Kushen alkaloids (KS-As) and Kushen flavonoids (KS-Fs) are the well characterized
      components in KS. KS-As have been considered biologically active and developed in
      China as anticancer drugs. In an effort to screen novel antitumor agents from
      botanicals, more potent antitumor activities were identified in KS-Fs than in KS
      As. KS-Fs were able to inhibit the growth of a panel of tumor cell lines and
      enhanced the antitumor activities of Taxol in vitro. The antitumor activities of
      KS-Fs and Kur, a single KS-Fs compound, were demonstrated in murine and xenograft
      human tumor models. Further, it was shown that KS-Fs and Kur were able to enhance
      the effect of Taxol to inhibit the growth of H460 and Eca-109 xenograft tumors.
      In addition, peripheral blood cell counts were not significantly affected in
      normal mice treated with KS-Fs at 200 mg/kg/day for 2 weeks. These results
      suggest that KS-Fs may be developed as novel antitumor agents and that the
      currently marketed KS-As drugs in China may have missed the major antitumor
      activities in Kushen.

PMID- 17186495
TI  - Italian Rett database and biobank.
AB  - Rett syndrome is the second most common cause of severe mental retardation in
      females, with an incidence of approximately 1 out of 10,000 live female births.
      In addition to the classic form, a number of Rett variants have been described.
      MECP2 gene mutations are responsible for about 90% of classic cases and for a
      lower percentage of variant cases. Recently, CDKL5 mutations have been identified
      in the early onset seizures variant and other atypical Rett patients. While the
      high percentage of MECP2 mutations in classic patients supports the hypothesis of
      a single disease gene, the low frequency of mutated variant cases suggests
      genetic heterogeneity. Since 1998, we have performed clinical evaluation and
      molecular analysis of a large number of Italian Rett patients. The Italian Rett
      Syndrome (RTT) database has been developed to share data and samples of our RTT
      collection with the scientific community (http://www.biobank.unisi.it). This is
      the first RTT database that has been connected with a biobank. It allows the user
      to immediately visualize the list of available RTT samples and, using the "Search
      by" tool, to rapidly select those with specific clinical and molecular features.
      By contacting bank curators, users can request the samples of interest for their
      studies. This database encourages collaboration projects with clinicians and
      researchers from around the world and provides important resources that will help
      to better define the pathogenic mechanisms underlying Rett syndrome.

PMID- 17186496
TI  - Obestatin-mediated proliferation of human retinal pigment epithelial cells:
      regulatory mechanisms.
AB  - In this work, we have evaluated the effect of the new discovered peptide
      obestatin on cell proliferation in primary cultures of human retinal epithelial
      cells (hRPE cells). The results showed that this peptide induced, in a dose
      dependent manner, cell proliferation by MEK/ERK 1/2 phosphorylation. A sequential
      analysis of the obestatin transmembrane signaling pathway showed that the ERK 1/2
      activity is partially blocked after preincubation of the cells with pertussis
      toxin (PTX), as well as by wortmannin (an inhibitor of PI3K), claphostin C (an
      inhibitor of PKC), and PP2 (which inhibits the non receptor tyrosine kinase Src).
      Upon administration of obestatin, the intracellular levels of phospho-PKCepsilon
      , theta-, and micro-isoenzymes rise with different time courses, from which
      PKCepsilon might be responsible for ERK 1/2 response. Based on the experimental
      data, a signaling pathway involving the consecutive activation of Gi, PI3K, novel
      PKC (probably PKCepsilon), and Src for ERK 1/2 activation is proposed. These
      results incorporate a new mitogenic factor to the group of factors that regulate
      proliferation of hRPE cells.

PMID- 17186498
TI  - Activation of Prn-p gene and stable transfection of Prn-p cDNA in leukemia MEL
      and neuroblastoma N2a cells increased production of PrP(C) but not prevented DNA
      fragmentation initiated by serum deprivation.
AB  - Prion protein (PrP(C)) via its isoform PrP(SC) is involved in the pathogenesis of
      transmissible spongiform encephalopathies (TSEs). We observed that murine
      erythroleukemia (MEL) cells arrested in phase G(1) undergo transcriptional
      activation of Prn-p gene. Here, we explored the potential role of activation of
      Prn-p gene and cytosolic accumulation of PrP(C) in growth arrest,
      differentiation, and apoptotic DNA fragmentation by stably transfecting MEL and
      N2a cells with Prn-p cDNA. Stably transfected MEL cells (clones # 6, 12, 20, 38,
      and 42) were assessed for growth and differentiation, while clones N2a13 and N2a8
      of N2a cells for growth and apoptosis by flow cytometry using Annexin V and
      propidium iodide (PI). Our results indicate that (a) Induction of terminal
      differentiation of stably transfected MEL cells led to growth arrest, activation
      of Prn-p gene, concomitant expression of transfected Prn-p cDNA, suppression of
      bax gene, cytosolic accumulation of PrP(C), and DNA fragmentation. The latter was
      also induced in non-differentiated MEL cells growing under serum-free conditions;
      (b) similarly, serum deprivation promoted growth arrest, apoptosis/necrosis
      associated with DNA fragmentation in parental N2a and N2a13 cells that produced
      relative high level of PrP(C) and not PrP(SC). These data indicate that
      activation of Prn-p gene and expression of transfected Prn-p cDNA in cells of
      both hematopoietic and neuronal origin occurred concomitantly, and led to
      cytosolic accumulation of PrP(C) and DNA damage induced by serum deprivation.
      PrP(C) production failed to protect DNA fragmentation induced by serum
      deprivation. The question how does PrP(C) contribute to growth arrest and DNA
      fragmentation is discussed.

PMID- 17186497
TI  - Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt
      signaling in mesangial cells.
AB  - Reactive oxygen species (ROS) contribute to many glomerular diseases by targeting
      mesangial cells. ROS have been shown to regulate expression of many antioxidant
      enzymes including catalase. The mechanism by which the expression of catalase
      protein is regulated by ROS is not precisely known. Here we report that increased
      intracellular ROS level by hydrogen peroxide (H(2)O(2)) reduced the expression of
      catalase. H(2)O(2) increased phosphorylation of Akt kinase in a dose-dependent
      and sustained manner with a concomitant increase in the phosphorylation of FoxO1
      transcription factor. Further analysis revealed that H(2)O(2) promoted rapid
      activation of phosphatidylinositol (PI) 3 kinase. The PI 3 kinase inhibitor
      Ly294002 and expression of tumor suppressor protein PTEN inhibited Akt kinase
      activity, resulting in the attenuation of FoxO1 phosphorylation and preventing
      the downregulating effect of H(2)O(2) on catalase protein level. Dominant
      negative Akt attenuated the inhibitory effect of H(2)O(2) on expression of
      catalase. Constitutively active FoxO1 increased the expression of catalase.
      However, dominant negative FoxO1 inhibited catalase protein level. Catalase
      transcription was reduced by H(2)O(2) treatment. Furthermore, expression of
      dominant negative Akt and constitutively active FoxO1 increased catalase
      transcription, respectively. These results demonstrate that ROS downregulate the
      expression of catalase in mesangial cells by PI 3 kinase/Akt signaling via FoxO1
      as a target.

PMID- 17186499
TI  - Impaired activity of volume-sensitive Cl- channel is involved in cisplatin
      resistance of cancer cells.
AB  - The platinum-based drug cisplatin is a widely used anticancer drug which acts by
      causing the induction of apoptosis. However, resistance to the drug is a major
      problem. In this study we show that the KCP-4 human epidermoid cancer cell line,
      which serves as a model of acquired resistance to cisplatin, has virtually no
      volume-sensitive, outwardly rectifying (VSOR) chloride channel activity. The VSOR
      chloride channel's molecular identity has not yet been determined, and semi
      quantitative RT-PCR experiments in this study suggested that the channel
      corresponds to none of three candidate genes. However, because it is known that
      the channel current plays an essential role in apoptosis, we hypothesized that
      lack of the current contributes to cisplatin resistance in these cells and that
      its restoration would reduce resistance. To test this hypothesis, we attempted to
      restore VSOR chloride current in KCP-4 cells. It was found that treatment with
      trichostatin A (TSA), a histone deacetylase inhibitor, caused VSOR chloride
      channel function to be partially restored. Treatment of the cells with both TSA
      and cisplatin resulted in an increase in caspase-3 activity at 24 h and a
      decrease in cell viability at 48 h. These effects were blocked by simultaneous
      treatment of the cells with a VSOR chloride channel blocker. These results
      indicate that restoration of the channel's functional expression by TSA treatment
      leads to a decrease in the cisplatin resistance of KCP-4 cells. We thus conclude
      that impaired activity of the VSOR chloride channel is involved in the cisplatin
      resistance of KCP-4 cancer cells.

PMID- 17186500
TI  - P2Y2 receptors induced cell surface redistribution of alpha(v) integrin is
      required for activation of ERK 1/2 in U937 cells.
AB  - Nucleotides released from cells due to stress, injury or inflammation, induce
      mitogenic effects in monocytes via activation of P2Y(2) nucleotide receptors
      (P2Y(2)Rs). Here we show that P2Y(2) nucleotide receptors in U937 monocytic cells
      regulate the activation of extracellular signal-regulated kinases 1 and 2 (ERK
      1/2) by inducing the clustering of alpha(v) integrins. The activation of
      phosphatidylinositol 3-kinase by P2Y(2)R ligands was required for alpha(v)
      clustering, suggesting a means whereby two different classes of receptors
      communicate to induce mitogenic responses in monocytic cells. P2Y(2)R-induced
      alpha(v) clustering was also associated with a flattened phenotype of the U937
      cells, consistent with the role of the P2Y(2)R in regulating early events in cell
      migration.

PMID- 17186501
TI  - A comparison of regression trees, logistic regression, generalized additive
      models, and multivariate adaptive regression splines for predicting AMI
      mortality.
AB  - Clinicians and health service researchers are frequently interested in predicting
      patient-specific probabilities of adverse events (e.g. death, disease recurrence,
      post-operative complications, hospital readmission). There is an increasing
      interest in the use of classification and regression trees (CART) for predicting
      outcomes in clinical studies. We compared the predictive accuracy of logistic
      regression with that of regression trees for predicting mortality after
      hospitalization with an acute myocardial infarction (AMI). We also examined the
      predictive ability of two other types of data-driven models: generalized additive
      models (GAMs) and multivariate adaptive regression splines (MARS). We used data
      on 9484 patients admitted to hospital with an AMI in Ontario. We used repeated
      split-sample validation: the data were randomly divided into derivation and
      validation samples. Predictive models were estimated using the derivation sample
      and the predictive accuracy of the resultant model was assessed using the area
      under the receiver operating characteristic (ROC) curve in the validation sample.
      This process was repeated 1000 times-the initial data set was randomly divided
      into derivation and validation samples 1000 times, and the predictive accuracy of
      each method was assessed each time. The mean ROC curve area for the regression
      tree models in the 1000 derivation samples was 0.762, while the mean ROC curve
      area of a simple logistic regression model was 0.845. The mean ROC curve areas
      for the other methods ranged from a low of 0.831 to a high of 0.851. Our study
      shows that regression trees do not perform as well as logistic regression for
      predicting mortality following AMI. However, the logistic regression model had
      performance comparable to that of more flexible, data-driven models such as GAMs
      and MARS.

PMID- 17186503
TI  - The Bethesda Interobserver Reproducibility Study (BIRST): a web-based assessment
      of the Bethesda 2001 System for classifying cervical cytology.
AB  - BACKGROUND: The Bethesda System (TBS) along with its companion atlas was updated
      in 2001 to improve standardization, clarity, and reproducibility of cervical
      cytology reporting. METHODS: The authors used a novel web-based format to compare
      assessments of 77 images demonstrating a range of classical and borderline
      cytologic changes by a self-selected group of United States cytotechnologists (n
      = 216) and pathologists (n = 185). RESULTS: Participants were highly experienced,
      with 71.2% of cytotechnologists and 53.0% of pathologists reporting >10 years of
      practice. The mean percentage of exact agreement with the panel was slightly
      though significantly higher for cytotechnologists (57.0%) compared with
      pathologists (53.4%), adjusted for experience (P = .004); cervical cytology
      percentage effort (P = .0005); or cervical accession volume (P = .0002). Compared
      with the TBS panel, exact agreement was achieved for 55.1% of image ratings
      compared with 82.3% agreement at the level of Negative vs non-Negative for images
      with a single-panel interpretation. Agreement with the panel was highest for
      images classified as Low-Grade Squamous Intraepithelial Lesion and lowest for
      Atypical Squamous Cells qualified as either of Undetermined Significance or
      Cannot Exclude a High-Grade Squamous Intraepithelial Lesion. Reviewers were less
      sensitive in identifying high-grade glandular lesions than they were in
      identifying high-grade squamous lesions at any threshold (P < .001). CONCLUSIONS:
      Morphologic appearances of images were more important determinants than
      participants' academic or professional degrees with regard to interobserver
      reproducibility in classifying cervical cytology images. Experienced
      cytotechnologists and pathologists performed similarly. Participants achieved
      higher sensitivity for identifying high-grade squamous lesions than they did for
      high-grade glandular lesions. These findings demonstrated that web-based studies
      may be useful in assessing interobserver agreement in classifying images.

PMID- 17186502
TI  - Insulin-like growth factor type 1 receptor signaling in the cells of
      oligodendrocyte lineage is required for normal in vivo oligodendrocyte
      development and myelination.
AB  - Insulin-like growth factor-I (IGF-I) has been shown to be a potent agent in
      promoting the growth and differentiation of oligodendrocyte precursors, and in
      stimulating myelination during development and following injury. To definitively
      determine whether IGF-I acts directly on the cells of oligodendrocyte lineage, we
      generated lines of mice in which the type 1 IGF receptor gene (igf1r) was
      conditionally ablated either in Olig1 or proteolipid protein expressing cells
      (termed IGF1R(pre-oligo-ko) and IGF1R(oligo-ko) mice, respectively). Compared
      with wild type mice, IGF1R(pre-oligo-ko) mice had a decreased volume (by 35-55%)
      and cell number (by 54-70%) in the corpus callosum (CC) and anterior commissure
      at 2 and 6 weeks of age, respectively. IGF1R(oligo-ko) mice by 25 weeks of age
      also showed reductions, albeit less marked, in CC volume and cell number. Unlike
      astrocytes, the percentage of NG2(+) oligodendrocyte precursors was decreased by
      approximately 13% in 2-week-old IGF1R(pre-oligo-ko) mice, while the percentage of
      CC1(+) mature oligodendrocytes was decreased by approximately 24% in 6-week-old
      IGF1R(pre-oligo-ko) mice and approximately 25% in 25-week-old IGF1R(oligo-ko)
      mice. The reduction in these cells is apparently a result of decreased
      proliferation and increased apoptosis. These results indicate that IGF-I directly
      affects oligodendrocytes and myelination in vivo via IGF1R, and that IGF1R
      signaling in the cells of oligodendrocyte lineage is required for normal
      oligodendrocyte development and myelination. These data also provide a
      fundamental basis for developing strategies with the potential to target IGF
      IGF1R signaling pathways in oligodendrocyte lineage cells for the treatment of
      demyelinating disorders.

PMID- 17186505
TI  - Triage of women with ASCUS and LSIL cytology: use of qualitative assessment of
      p16INK4a positive cells to identify patients with high-grade cervical
      intraepithelial neoplasia.
AB  - BACKGROUND: The identification of a small percentage of high-grade cervical
      intraepithelial neoplasias (HGCIN) among patients with minor cytological
      abnormalities (atypical squamous cells of undetermined significance [ASCUS]
      and/or low-grade squamous intraepithelial lesions [LSIL] group) is a major
      problem in cytology-based cervical cancer screening. The authors investigated the
      efficacy of p16INK4a as a biomarker to identify samples of patients with HGCIN
      among those with an ASCUS or LSIL result in Papanicolaou cytology. METHODS:
      Consecutive liquid-based cytology specimens of 137 ASCUS and 88 LSIL results were
      selected from gynecologists who adopted a triage regimen with biopsy under
      colposcopy 2 months later, independent of the p16INK4a result. p16INK4a stained
      slides were prepared and independently read by 2 observers, who used a recently
      described score to categorize p16INK4a stained squamous cells. The endpoint of
      the study was detection of a biopsy-confirmed HGCIN. RESULTS: The overall
      sensitivity and specificity of p16INK4a positive cells with a nuclear score >2
      for diagnosis of HGCIN in ASCUS and LSIL cases combined was 96% and 83%,
      respectively. The sensitivity and specificity in the ASCUS group was 95% and 84%,
      and 100% and 81% in the LSIL group, respectively. Two observers had a high
      concordance in assessing p16INK4a stained cells (kappa value of 0.841).
      CONCLUSIONS: These data suggested that the use of p16INK4a as a biomarker
      combined with nuclear scoring of p16INK4a positive cells in cervical cytology to
      triage ASCUS and/or LSIL cases allows identification of HGCIN with good
      sensitivity and specificity.

PMID- 17186506
TI  - On staphylococcal prophylaxis in CF.

PMID- 17186507
TI  - Temporal relationship of asthma to acute chest syndrome in sickle cell disease.
AB  - Acute chest syndrome (ACS) is an important cause of mortality and morbidity in
      children with sickle cell disease (SCD). An association between asthma and ACS
      has been reported. Our aims were to determine whether asthma was more common in
      SCD children than controls and the relationship of the timing of the SCD
      children's first ACS episode to a diagnosis of asthma. One hundred and sixty-five
      SCD children median age 8.2 (range 0.3-17.3) years and 151 similar ethnic origin
      and aged controls were prospectively recruited into the study and a detailed
      history was taken from all of the children to determine if they were taking anti
      asthma medication. The medical records of the SCD children were examined to
      assess whether they had an ACS episode, the age this episode occurred and when
      any diagnosis of asthma had been made. A similar proportion of the SCD children
      and controls were taking anti-asthma medication (7% and 9%). Thirty-three SCD
      children had at least one ACS episode. More of the children who had an ACS
      compared to those who had not were taking anti-asthma medication (P = 0.02). The
      ACS children had been diagnosed as asthmatic at a median of 3.5 (range 0.5-7)
      years prior to their first ACS episode. In conclusion, these results suggest
      asthma exacerbations may predispose to ACS episodes.

PMID- 17186508
TI  - Low gammaglobulin subclass 2 levels in paediatric cystic fibrosis patients
      followed over a 2-year period.
AB  - The aim of this study was to relate serum immunoglobulin G2 subclass levels in a
      large paediatric population with cystic fibrosis, to clinical status and antibody
      levels to Haemophilus influenzae type b and Streptococcus pneumoniae and to
      observe any changes over a 2-year period. IgG subclasses were measured in 131
      patients. Results were compared with levels from age-related normal population
      data. The following clinical data were collected at baseline and 2 years later;
      genotype: height, weight, and BMI z-scores: FEV1 (as percent predicted):
      Shwachman-Kulczcyki and Northern chest X-ray scores: Pseudomonas aeruginosa
      status. Antibody levels to H. influenzae type b and S. pneumoniae measured at
      baseline were related to IgG2 level. There was a reduction in the prevalence of
      low levels of IgG2 from 29% to 10% over the 2-year period. Low levels of IgG2
      were not associated with any decline in clinical well-being. Low levels of IgG2
      alone were associated with low antibody levels to S. pneumoniae. Low levels of
      IgG2 and low levels of antibody to H. influenzae and S. pneumoniae were not
      associated with any decline in clinical well-being. Children with high levels of
      IgG2 had worse lung function, worse Shwachman-Kulczcyki and Northern chest X-ray
      scores and higher levels of P. aeruginosa infection. Children with low IgG2
      levels were not worse clinically compared to those with normal or high IgG2
      levels. High IgG2 levels were associated with a worse clinical status.

PMID- 17186509
TI  - Lung function and exhaled nitric oxide levels in infants developing chronic lung
      disease.
AB  - Chronic lung disease (CLD) is a common outcome of neonatal intensive care. To
      determine whether the results of serial exhaled nitric oxide (eNO) measurements
      during the perinatal period differed between infants who did and did not develop
      CLD. In addition, we wished to assess whether eNO results were more predictive of
      CLD development than lung function test results or readily available clinical
      data (gestational age and birthweight). The patients were 24 infants with a
      median gestational age of 27 (range 25-31) weeks. Measurements of eNO levels,
      functional residual capacity (FRC), and compliance of the respiratory system
      (CRS) were attempted on postnatal days 1, 3, 5, 7, 14, and 28 days. The 12
      infants who developed CLD were of significantly lower birthweight and gestational
      age than the rest of the cohort; in addition, they had lower median FRC (P <
      0.02) and CRS (P < 0.02) results, but not higher eNO levels, in the first week
      after birth. Construction of receiver operator characteristic (ROC) curves
      demonstrated that the CRS and FRC results on Day 3 were the best predictors of
      CLD development; the areas under the ROC curves were 0.94 and 0.91, respectively.
      Early lung function test results, but not eNO levels, are useful in predicting
      CLD development, but are not significantly better than birthweight.

PMID- 17186510
TI  - The three faces of Jay S. Rosenblatt.
AB  - This essay provides an account of the development of Jay S. Rosenblatt's approach
      and contributions to the study of maternal behavior and the mother-young
      relationship, focusing on the role in that development of his life as painter,
      analyst, and scientist. It is personal perspective.

PMID- 17186511
TI  - Can knowledge of developmental processes illuminate the evolution of parental
      care?
AB  - There are two levels of investigation for elucidating the evolution of parental
      behavior. The macro level focuses on how parental behavior can evolve as an
      aspect of reproduction. The micro level focuses on how species variations in
      parental behavior evolve. Recently, modern evolutionary biology has turned to
      developmental biology as a source for information about how trait variability
      (the substrate upon which natural selection and other evolutionary mechanisms can
      operate) can emerge during development (called "evo-devo"). Application of this
      evo-devo approach to the phenomenon of parental behavior requires identification
      of those mechanisms that produce variations in developmental pathways leading to
      parental behavior. It is these variations that provide the phenotypes for the
      potential evolution of different parental behavior systems. Variations in rodent
      maternal behavior affect the development of the HPA and HPG axes in their
      offspring. These mechanisms are examined to reveal how such developmental
      variations could underlie the evolution of biparental behavior. Knowledge of the
      developmental mechanisms responsible for species variations in mammalian parental
      behavior systems may provide insight into those mechanisms that may have been
      involved in the evolution of parental behavior itself.

PMID- 17186512
TI  - Influence of the mother in the development of flavored-food preference in lambs.
AB  - The aim of the study was to determine the influence of the mother in the
      development of flavored-food preference in lambs. First, we demonstrated that
      lambs that ate flavored food in the presence of their mothers before weaning ate
      more of this food 1 month after weaning than lambs that ate flavored food with
      other ewes or lambs exposed to nonflavored food with their mothers. Second, lambs
      that could only see their mothers eating the flavored food and had access to the
      food's olfactory cues before weaning, showed similar preference for flavored food
      1 month after weaning to lambs that ate the flavored food with their mothers.
      However, lambs that were separated from their mothers while their mothers
      consumed flavored food did not reveal a preference for it. Overall these results
      suggest that development of food preference in lambs depends mainly on
      observation of the mother, provided there is also access to olfactory cues
      characterizing the food.

PMID- 17186513
TI  - Motivational systems and the neural circuitry of maternal behavior in the rat.
AB  - Jay Rosenblatt's approach-avoidance model of maternal behavior proposes that
      maternal behavior occurs when the tendency to approach infant stimuli is greater
      than the tendency to avoid such stimuli. Our research program has uncovered
      neural circuits which conform to such a model. We present evidence that the
      medial preoptic area (MPOA: located in the rostral hypothalamus) may regulate
      maternal responsiveness by depressing antagonistic neural systems which promote
      withdrawal responses while also activating appetitive neural systems which
      increase the attractiveness of infant-related stimuli. These MPOA circuits are
      activated by the hormonal events of late pregnancy. Preoptic efferents may
      suppress a central aversion system which includes an amygdala to anterior
      hypothalamic circuit. Preoptic efferents are also shown to interact with
      components of the mesolimbic dopamine (DA) system to regulate proactive voluntary
      maternal responses. We make a distinction between specific (MPOA neurons) and
      nonspecific motivational systems (mesolimbic DA system) in the regulation of
      maternal responsiveness.

PMID- 17186515
TI  - Maternal behavior, infant development, and the question of developmental
      resources.
AB  - The natural development of maternal and infant behavior occurs in a dyad
      characterized by synchrony and reciprocal interactions. Major concepts used to
      describe and analyze this synchrony were reviewed. It was concluded that the dyad
      undergoes a developmental progression in which each part of the dyad is both a
      developing organism and a reliably changing milieu forming part of the extended
      inheritance of the other. The reliability of inherited resources is rooted in
      interactions essential to life, such as those used to transfer metabolic needs to
      dependent offspring; to stimulation (incidentally but necessarily) associated
      with life-supporting mechanisms; and to perceptual, motor, or learning mechanisms
      used to extract specific resources from the available milieu. The diverse
      resources in extended inheritance contribute to the construction of new traits
      through opportunistic shaping or regulating interactions among them that are
      unrestricted by their function at earlier stages.

PMID- 17186514
TI  - Huddling by rat pups: ontogeny of individual and group behavior.
AB  - A full account of behavioral development in rats must include the ontogeny of
      both individual and group behavior. Most of our accumulated knowledge, however,
      pertains to individual ontogenesis. Group behavior and its development are
      readily seen in the huddling behavior of rat pups. A rat huddle is an entity with
      characteristics and capabilities distinct from those of the individuals that
      comprise it. The huddle is a natural context for acquiring olfactory preferences
      for species odors. Olfactory learning in a huddle involves thermal and tactile
      stimulation from the mother's body but, surprisingly, not the rewards of suckling
      or of milk transfer. Although there is complete developmental continuity of
      huddling behavior, the sensory controls of huddling change dramatically during
      the first 2 weeks of postnatal life. Huddling behavior is initially controlled by
      thermal cues ("physiological huddling") and then becomes dominated by olfactory
      stimuli ("filial huddling"). The complex group behavior of huddling was modeled
      successfully with computational methods. Group behavior emerges from individual
      interactions, guided entirely by rules of individual behavior (no rules for group
      behavior). Three simple rules of autonomous activity/inactivity can spawn the
      patterns of aggregon formation displayed by groups of 7-day-old pups, but not by
      10-day-olds. The developmental change evident by Day 10 requires adding a rule by
      which each individual is affected by the activity state of adjacent pups. Group
      behavior responded to manipulations of central oxytocin on Day 10, but not on Day
      7.

PMID- 17186516
TI  - Maternal responsiveness and maternal selectivity in domestic sheep and goats: the
      two facets of maternal attachment.
AB  - Sheep and goats rapidly establish an exclusive relationship with their neonate
      following contact with it during a sensitive period of maternal responsiveness
      induced by the physiological events occurring at parturition. The data concerning
      the sensory, physiological, and neurobiological factors involved in the
      activation of both maternal responsiveness and the establishment of selective
      nursing indicates that these processes are activated simultaneously by the
      combined action of two main factors, the prepartum rise in circulating estrogen
      and the vaginocervical stimulation (VCS) caused by fetus expulsion. On the one
      hand, these two factors act on a neural network including the main olfactory
      system (MOB), the medial preoptic area (MPOA), and the paraventricular nucleus of
      the hypothalamus (PVN) to induce maternal responsiveness towards any neonate. The
      intracerebral release of oxytocin (OT) from the PVN, and the triggering of
      olfactory attraction for amniotic fluid (AF) are key elements in this process. On
      the other hand, VCS at birth also sets the MOB ready to memorize the individual
      odor of the neonate, through the release of peptides and neurotransmitters
      (noradrenaline and acetylcholine). In addition to the MOB, the network involved
      in recognition mainly includes the medial and cortical amygdala. Across
      consolidation processes, reorganization occurs in the network engaged in lamb
      recognition. Whether this memorization may be potentiated by other sensory cues
      is not known. The identification of the chemosensory compounds involved in the
      attraction for AF and in the recognition of the neonate is important for
      understanding the mechanisms of maternal attachment.

PMID- 17186517
TI  - Mother rabbits and their offspring: timing is everything.
AB  - Mother rabbits nurse once every 24 hr for ca. 3 min. The contribution of pup
      stimulation to the regulation of this process was investigated by: reducing
      litter size to one pup, covering all the mother's nipples, or taping the mouths
      of an eight-pup litter. Time inside the nest box with the young significantly
      increased under all these conditions. Yet, eight pups sucking on a single nipple
      allowed a normal time in the nest box. Bringing the litter to the mother earlier
      than usual promoted maternal behavior expression twice in 24 hr; the proportion
      of responsive females and the time at which they responded depended on the size
      of the litter suckled. These findings indicate that: (a) suckling determines the
      time inside the nest box and prevents mothers from responding to further pup
      stimulation for a variable time; (b) pup exposure promotes maternal behavior,
      even "out of phase" with circadian rhythmicity.

PMID- 17186518
TI  - Proceedings of a symposium in recognition of Professor Jay S. Rosenblatt held at
      the 2005 meeting of the International Society for Developmental Psychobiology.

PMID- 17186519
TI  - Developing a framework for development: a discussion.
AB  - A multitude of scientific disciplines study the development of behavior. Their
      use of different methodological and conceptual approaches makes integration of
      findings difficult. In a symposium at the 38th Annual Meeting of the
      International Society for Developmental Psychobiology in Washington DC, the
      question was discussed if a general theory of development could unify the field.
      The three participants explain their views and discuss the possibility of a
      theoretical framework for development.

PMID- 17186520
TI  - Characterization of offensive responses during the maturation of play-fighting
      into aggression in male golden hamsters.
AB  - In hamsters, the maturation of aggression during puberty is associated with a
      gradual reduction of offensive responses. The purpose of this study was to
      analyze the changes during this decrease to provide an enhanced description of
      the behavior. During early puberty, play-fighting is characterized by long and
      continuous contact duration throughout the encounter and repetitive attacks
      within bouts of agonistic interaction. By mid-puberty, adult patterns of
      offensive behavior emerge. Contact time becomes shorter in duration and shifts to
      the beginning of the test, while attacks become less repetitive per bout. In late
      puberty, animals show an enhanced efficiency of behavior, as indicated by an
      increased percentage of attacks followed by bites. This study provides a better
      understanding of the development of aggression by characterizing the differences
      between juvenile play-fighting and adult aggression and the process of the
      maturation of aggression.

PMID- 17186521
TI  - Bone marrow mononuclear cells stimulate angiogenesis when transplanted into
      surgically induced fibrocollagenous tunnels: results from a canine ischemic
      hindlimb model.
AB  - Progenitor cell transplantation has been considered as a potential angiogenesis
      therapy for the ischemic hindlimb. In this work we performed an ischemic hindlimb
      model in dogs. We ligated the middle sacra and the external right iliac arteries.
      After 7 days, the femoral artery was ligated and removed, and three Silastic
      tubes were inserted into the gracilis muscle to create fibrocollagenous tunnels.
      After Silastic implantation, we administered saline or granulocyte colony
      stimulating factor (G-CSF) subcutaneously daily during 5 days. Fourteen days
      after device positioning we transplanted bone marrow mononuclear cells (BMMC)
      into the tunnels previously formed by Silastic tube reaction. Twenty-eight days
      later, contrasted angiographies were performed and angiographic scores were
      calculated. Also, vessels and endothelial cells and proliferating cells were
      identified by immunochemistry of muscle sections. Results demonstrated that BMMC
      transplantation enriched by G-CSF administration significantly stimulates
      angiogenesis in the ischemic hindlimb, and more than BMMC transplantation alone.
      Transplantation of progenitor cells in an appropriate extracellular matrix is a
      potential therapy for hindlimb ischemia.

PMID- 17186524
TI  - The mutations Lys 114 --> Gln and Asp 126 --> Asn disrupt an intersubunit salt
      bridge and convert Listeria innocua Dps into its natural mutant Listeria
      monocytogenes Dps. Effects on protein stability at Low pH.
AB  - The stability of the dodecameric Listeria monocytogenes Dps has been compared
      with that of the Listeria innocua protein. The two proteins differ only in two
      amino acid residues that form an intersubunit salt-bridge in L. innocua Dps. This
      salt-bridge is replaced by a hydrogen bonding network in L. monocytogenes Dps as
      revealed by the X-ray crystal structure. The resistance to low pH and high
      temperature was assayed for both Dps proteins under equilibrium conditions and
      kinetically. Despite the identical equilibrium behavior, significant differences
      in the kinetic stability and activation energy of the unfolding process are
      apparent at pH 1.5. The higher stability of L. monocytogenes Dps has been
      accounted for in terms of the persistence of the hydrogen bonding network at this
      low pH value. In contrast, the salt-bridge between Lys 114 and Asp 126
      characteristic of L. innocua Dps is most likely abolished due to protonation of
      Asp 126.

PMID- 17186523
TI  - X-ray structure of the T. aquaticus FtsY:GDP complex suggests functional roles
      for the C-terminal helix of the SRP GTPases.
AB  - FtsY and Ffh are structurally similar prokaryotic Signal Recognition Particle
      GTPases that play an essential role in the Signal Recognition Particle (SRP)
      mediated cotranslational targeting of proteins to the membrane. The two GTPases
      assemble in a GTP-dependent manner to form a heterodimeric SRP targeting complex.
      We report here the 2.1 A X-ray structure of FtsY from T. aquaticus bound to GDP.
      The structure of the monomeric protein reveals, unexpectedly, canonical binding
      interactions for GDP. A comparison of the structures of the monomeric and
      complexed FtsY NG GTPase domain suggests that it undergoes a conformational
      change similar to that of Ffh NG during the assembly of the symmetric
      heterodimeric complex. However, in contrast to Ffh, in which the C-terminal helix
      shifts independently of the other subdomains, the C-terminal helix and N domain
      of T. aquaticus FtsY together behave as a rigid body during assembly, suggesting
      distinct mechanisms by which the interactions of the NG domain "module" are
      regulated in the context of the two SRP GTPases.

PMID- 17186525
TI  - Protein-RNA interactions: structural analysis and functional classes.
AB  - A data set of 89 protein-RNA complexes has been extracted from the Protein Data
      Bank, and the nucleic acid recognition sites characterized through direct
      contacts, accessible surface area, and secondary structure motifs. The
      differences between RNA recognition sites that bind to RNAs in functional classes
      has also been analyzed. Analysis of the complete data set revealed that van der
      Waals interactions are more numerous than hydrogen bonds and the contacts made to
      the nucleic acid backbone occur more frequently than specific contacts to
      nucleotide bases. Of the base-specific contacts that were observed, contacts to
      guanine and adenine occurred most frequently. The most favored amino acid
      nucleotide pairings observed were lysine-phosphate, tyrosine-uracil, arginine
      phosphate, phenylalanine-adenine and tryptophan-guanine. The amino acid
      propensities showed that positively charged and polar residues were favored as
      expected, but also so were tryptophan and glycine. The propensities calculated
      for the functional classes showed trends similar to those observed for the
      complete data set. However, the analysis of hydrogen bond and van der Waal
      contacts showed that in general proteins complexed with messenger RNA, transfer
      RNA and viral RNA have more base specific contacts and less backbone contacts
      than expected, while proteins complexed with ribosomal RNA have less base
      specific contacts than the expected. Hence, whilst the types of amino acids
      involved in the interfaces are similar, the distribution of specific contacts is
      dependent upon the functional class of the RNA bound.

PMID- 17186522
TI  - NTP-CERHR expert panel report on the reproductive and developmental toxicity of
      genistein.

PMID- 17186526
TI  - Locating missing water molecules in protein cavities by the three-dimensional
      reference interaction site model theory of molecular solvation.
AB  - Water molecules confined in protein cavities are of great importance in
      understanding the protein structure and functions. However, it is a nontrivial
      task to locate such water molecules in protein by the ordinary molecular
      simulation and modeling techniques as well as experimental methods. The present
      study proves that the three-dimensional reference interaction site model (3D
      RISM) theory, a recently developed statistical-mechanical theory of molecular
      solvation, has an outstanding advantage in locating such water molecules. In this
      paper, we demonstrate that the 3D-RISM theory is able to reproduce the structure
      and the number of water molecules in cavities of hen egg-white lysozyme observed
      commonly in the X-ray structures of different resolutions and conditions.
      Furthermore, we show that the theory successfully identified a water molecule in
      a cavity, the existence of which has been ambiguous even from the X-ray results.
      In contrast, we confirmed that molecular dynamics simulation is helpless at
      present to find such water molecules because the results substantially depend on
      the initial coordinates of water molecules. Possible applications of the theory
      to problems in the fields of biochemistry and biophysics are also discussed.

PMID- 17186527
TI  - Evaluating protein structures determined by structural genomics consortia.
AB  - Structural genomics projects are providing large quantities of new 3D structural
      data for proteins. To monitor the quality of these data, we have developed the
      protein structure validation software suite (PSVS), for assessment of protein
      structures generated by NMR or X-ray crystallographic methods. PSVS is broadly
      applicable for structure quality assessment in structural biology projects. The
      software integrates under a single interface analyses from several widely-used
      structure quality evaluation tools, including PROCHECK (Laskowski et al., J Appl
      Crystallog 1993;26:283-291), MolProbity (Lovell et al., Proteins 2003;50:437
      450), Verify3D (Luthy et al., Nature 1992;356:83-85), ProsaII (Sippl, Proteins
      1993;17: 355-362), the PDB validation software, and various structure-validation
      tools developed in our own laboratory. PSVS provides standard constraint
      analyses, statistics on goodness-of-fit between structures and experimental data,
      and knowledge-based structure quality scores in standardized format suitable for
      database integration. The analysis provides both global and site-specific
      measures of protein structure quality. Global quality measures are reported as Z
      scores, based on calibration with a set of high-resolution X-ray crystal
      structures. PSVS is particularly useful in assessing protein structures
      determined by NMR methods, but is also valuable for assessing X-ray crystal
      structures or homology models. Using these tools, we assessed protein structures
      generated by the Northeast Structural Genomics Consortium and other international
      structural genomics projects, over a 5-year period. Protein structures produced
      from structural genomics projects exhibit quality score distributions similar to
      those of structures produced in traditional structural biology projects during
      the same time period. However, while some NMR structures have structure quality
      scores similar to those seen in higher-resolution X-ray crystal structures, the
      majority of NMR structures have lower scores. Potential reasons for this
      "structure quality score gap" between NMR and X-ray crystal structures are
      discussed.

PMID- 17186528
TI  - Cumulative cost pattern comparison of prostate cancer treatments.
AB  - BACKGROUND: Studies that compare prostate cancer treatment costs show wide
      variation. None compare all contemporary treatment costs, and most focus on
      initial treatment costs. The authors compared healthcare utilization and cost
      patterns of prostate cancer treatments over a span of 5.5 years in 4553 newly
      diagnosed patients stratified by age and risk group. METHODS: Contemporary
      treatment and evaluation patterns for prostate cancer were identified by using
      CaPSURE, a national disease registry of men with prostate cancer that included
      ongoing clinical data collection from 31 academic and community urology practices
      and biennial patient-reported outcome questionnaires that included demography,
      medical condition, comorbidity, risk measures, and healthcare utilization. Costs
      of outpatient visits, medications, and hospitalizations were applied from various
      national sources. Recurrent events analysis (MCF) accounted for left and right
      censorship. A mixed effects regression model with bootstrapping for skewed cost
      data quantified the relation between MCF cost, age, and risk. RESULTS: Prostate
      related costs in the first 6 months after treatment were 11,495 dollars, (from
      2586 dollars for watchful waiting (WW) to 24,204 dollars for external beam
      radiation. After 6 months, average cost was only 3044 dollars. Annual cost is
      7740 dollars, highest for androgen deprivation therapy (12,590 dollars) and
      lowest for watch waiting (5843 dollars). Risk and age were significantly related
      to initial treatment choice. Cumulative cost (42,570 dollars) allowed a better
      estimate of treatment pattern costs. CONCLUSIONS: The cost burden of prostate
      cancer is high, but it varies by treatment type even when controlling for
      disease, age, and stage. Cumulative cost analysis allowed inclusion of adverse
      events and disease recurrence costs, making new cost comparisons evident among
      treatments.

PMID- 17186529
TI  - Racial differences in tumor stage and survival for colorectal cancer in an
      insured population.
AB  - BACKGROUND: Despite declining death rates from colorectal cancer (CRC), racial
      disparities have continued to increase. In this study, the authors examined
      disparities in a racially diverse group of insured patients. METHODS: This study
      was conducted among patients who were diagnosed with CRC from 1993 to 1998, when
      they were enrolled in integrated healthcare systems. Patients were identified
      from tumor registries and were linked to information in administrative databases.
      The sample was restricted to non-Hispanic whites (n = 10,585), non-Hispanic
      blacks (n = 1479), Hispanics (n = 985), and Asians/Pacific Islanders (n = 909).
      Differences in tumor stage and survival were analyzed by using polytomous and Cox
      regression models, respectively. RESULTS: In multivariable regression analyses,
      blacks were more likely than whites to have distant or unstaged tumors. In Cox
      models that were adjusted for nonmutable factors, blacks had a higher risk of
      death from CRC (hazard ratio [HR], 1.17; 95% confidence interval [95% CI], 1.06
      1.30). Hispanics had a risk of death similar to whites (HR, 1.04; 95% CI, 0.92
      1.18), whereas Asians/Pacific Islanders had a lower risk of death from CRC (HR,
      0.89; 95% CI, 0.78-1.02). Adjustment for tumor stage decreased the HR to 1.11 for
      blacks, and the addition of receipt of surgical therapy to the model decreased
      the HR further to 1.06. The HR among Hispanics and Asians/Pacific Islanders was
      stable to adjustment for tumor stage and surgical therapy. CONCLUSIONS: The
      relation between race and survival from CRC was complex and appeared to be
      related to differences in tumor stage and therapy received, even in insured
      populations. Targeted interventions to improve the use of effective screening and
      treatment among vulnerable populations may be needed to eliminate disparities in
      CRC.

PMID- 17186530
TI  - Underestimation of malignancy of breast core-needle biopsy: concepts and precise
      overall and category-specific estimates.
AB  - BACKGROUND: A review of the literature indicated variable underestimation rates
      for breast core-needle biopsy (CNB) based on generally small series. In this
      article, the authors present precise estimates for overall underestimation and
      for categories of histologic underestimates (including categories that reflect
      contemporary classification) and examine the effect of lesion and sampling
      variables. METHODS: Among 4035 consecutive CNBs, the authors examined women whose
      CNB outcome represented a potential underestimate of malignancy (benign but of
      uncertain biologic or malignant potential or B3 and ductal carcinoma in situ
      [DCIS]). From 889 eligible women, all 758 women who had excision histology
      available were included. RESULTS: Overall underestimation of CNB was 27.7% (95%
      confidence interval [95% CI], 24.5-30.9%). The following category-specific rates
      were used: B3 underestimates, 36.2% (95% CI, 30.6-41.8%); B3 underestimates
      (excluding atypical proliferations), 17.9% (95% CI, 10.8-24.9%); atypical ductal
      hyperplasia underestimates, 29.0% (95% CI, 21.4-36.6%; upgraded to DCIS) and
      44.2% (95% CI, 36.0-52.5%; upgraded to DCIS or invasive cancer); and DCIS
      underestimates, 22.8% (95% CI, 19.0-26.5%). There was a significant trend toward
      greater underestimation of malignancy with increasing lesion size on imaging
      studies for overall underestimates (P = .00008), B3 underestimates (P = .009),
      and DCIS underestimates (P = .0007). Underestimation rates did not differ between
      masses (27.9%) and microcalcifications (27.6%; chi-square statistic with 1 degree
      of freedom = 3.02; P = .98) and were significantly lower for vacuum-assisted CNB
      (11-gauge) than for automated CNB (14-gauge; P = .001). Underestimation rates,
      when sampling microcalcifications, decreased with increasing number of cores
      collected, but this was mainly for DCIS underestimates. CONCLUSIONS: CNB results
      that were not definitely negative or were not positive for invasive cancer were
      associated with high rates of underestimation of disease and with target lesion
      size. Identifying imaging or sampling factors that affect underestimation rates
      of CNB may assist in reducing their occurrence and better predicting excision
      histology outcomes.

PMID- 17186531
TI  - Is there a role for platinum chemotherapy in the treatment of patients with
      hormone-refractory prostate cancer?
AB  - Docetaxel chemotherapy is the current standard of care for metastatic hormone
      refractory prostate cancer (HRPC). Platinum chemotherapy drugs, such as cisplatin
      and carboplatin, have moderate single-agent activity in HRPC. Next-generation
      platinum drugs, including satraplatin and oxaliplatin, may have additional
      activity in the management of HRPC. Furthermore, neuroendocrine differentiation
      may play a role in disease progression, providing a rationale for platinum-based
      chemotherapy in the management of HRPC. The authors reviewed the MEDLINE database
      for reports related to platinum-based chemotherapy in patients with advanced
      prostate cancer and evaluated studies that reviewed the role of neuroendocrine
      differentiation in the progression of HRPC. Older studies from the 1970s and
      1980s suggested a lack of activity of cisplatin and carboplatin; however, those
      studies were flawed at least in part by their methods of response assessment.
      More recent Phase II studies of carboplatin suggested a moderate level of
      clinical and palliative activity when it was used as a single agent. However,
      when carboplatin was combined with a taxane and estramustine, high response rates
      were observed in several recent clinical trials. In addition, a randomized trial
      suggested that satraplatin plus prednisone improved progression-free survival
      compared with prednisone alone. For patients who progressed after docetaxel, no
      standard options existed in the literature that was reviewed. Several preliminary
      reports suggested that carboplatin and oxaliplatin may have activity as second
      line chemotherapy. Platinum chemotherapy drugs historically have been considered
      inactive in HRPC, although a review of the data suggested otherwise. Carboplatin,
      in particular, induced very high response rates when it was combined with
      estramustine and a taxane, but it also appeared to have activity in patients who
      progressed after docetaxel. Satraplatin plus prednisone is being investigated in
      a large Phase III trial as second-line chemotherapy for HRPC. Targeting
      neuroendocrine cells may provide a new therapeutic approach to HRPC.

PMID- 17186532
TI  - Identical epidermal growth factor receptor mutations in adenocarcinomatous and
      squamous cell carcinomatous components of adenosquamous carcinoma of the lung.
AB  - BACKGROUND: Adenosquamous carcinoma of the lung is composed of adenocarcinomatous
      and squamous cell carcinomatous components. The epidermal growth factor receptor
      (EGFR) mutations occur mostly in adenocarcinomas and rarely in squamous cell
      carcinoma of lung. Attempts to investigate the EGFR mutation status in each
      component of adenosquamous carcinoma and to characterize the patients according
      to mutation status may help to understand the histogenesis of adenosquamous
      carcinoma. METHODS: The mutation status of EGFR kinase domain from exon 18 to 21
      was investigated in 25 Korean patients with adenosquamous carcinoma by polymerase
      chain reaction-single strand conformation polymorphism using the tissues of each
      component from the adenosquamous carcinoma tumor. Clinicopathologic
      characteristics of the patients according to the status of EGFR mutations were
      compared. RESULTS: EGFR mutations were identified in 11 (44%) patients: 9
      mutations were in exon 19, 1 in exon 20, and 1 in exon 21. EGFR mutations were
      significantly more frequent (P = .005) in women (n = 8, 80%) than men (n = 3,
      20%). Never-smokers (n = 8, 62%) had EGFR mutations more commonly than smokers (n
      = 3, 25%; P = .111). Identical EGFR mutations in both components of adenosquamous
      carcinoma were confirmed by nucleotide sequencing. CONCLUSIONS: The frequency of
      EGFR mutation and clinicopathologic characteristics of the EGFR mutants in
      adenosquamous carcinoma are similar to those of Asian patients with
      adenocarcinomas. Identical EGFR mutations in both components suggest the
      possibility of monoclonality in the histogenesis of adenosquamous carcinoma.

PMID- 17186533
TI  - A systematic review of psychological interventions for children with asthma.
AB  - AIM: Psychological factors may influence the symptoms and management of asthma in
      children in many ways. It is, therefore, suggested that psychological
      interventions may be appropriate for this population. This paper reports a
      systematic review assessing the efficacy of psychological interventions in
      improving health outcomes for children with asthma. METHODOLOGY: A review of
      Randomized Controlled Trials (RCT) was designed. RCTs assessing the effects of a
      psychological intervention in child participants were included in the review.
      Outcome measures included healthcare utilization, lung function, asthma symptoms,
      and psychological health status. The search was conducted until April 2005.
      RESULTS: Twelve studies, involving 588 children, were included in the review;
      however, study quality was poor and sample sizes were frequently small. A meta
      analysis was performed on two studies, examining the effects of relaxation
      therapy on PEFR which favored the treatment group (SD 0.82, CI 0.41-1.24). No
      other meta-analysis could be performed due to the diversity of interventions and
      the outcomes assessed. In addition, many studies reported insufficient data.
      CONCLUSIONS: This review was unable to draw firm conclusions for the role of
      psychological interventions for children with asthma. We recommend that valid
      outcome measures for evaluating the effectiveness of psychological interventions
      for children with asthma need to address adjustment to and coping with asthma, as
      well as other psychological indicators. The absence of an adequate evidence base
      is demonstrated, highlighting the need for well-conducted RCTs in this area.

PMID- 17186534
TI  - Assessing bronchial responsiveness to hypertonic saline using the stepwise
      protocol of Phase Two of the International Study of Asthma and Allergies in
      Childhood (ISAAC II).
AB  - Measurement of bronchial responsiveness to hypertonic saline was applied in 22
      study centers worldwide as part of Phase Two of the International Study of Asthma
      and Allergies in Childhood (ISAAC Phase Two). Because the amount of inhaled
      saline was difficult to standardize during the stepwise protocol with inhalation
      periods of increasing duration, we evaluated different statistical procedures
      based on inhalation time in relation to wheeze and current asthma. Data on random
      samples on 9 to 11-year-old children (n = 1,418) from two German centers were
      analyzed. The following statistical approaches were evaluated: (1) bronchial
      hyperreactivity (BHR) defined dichotomously as a fall in FEV1 (forced expiratory
      volume in 1 s) >or=15%; (2) PT15: the provocation time causing BHR using survival
      analyses methods; (3) time-response-slope (continuous) of the individual FEV1
      courses calculated by a linear model after comparing different mathematical
      models. The sensitivity and specificity of BHR versus current asthma were 47% and
      87%, respectively. Analyses of the provocation time indicated an increased risk
      (adjusted hazard-ratio: 4.3; 95% CI: 2.8-6.5) for a fall in FEV1 >or= 15% among
      children with current asthma in comparison to those without. The time-response
      slope differed markedly between children with and without wheeze and current
      asthma (P < 0.0001). BHR is meaningful and relatively easy to use, but has low
      sensitivity. Time-response-slopes utilize the available information from the
      stepwise protocol better than BHR and survival-analysis based on PT15. Response
      parameters based on inhalation time discriminate well between children with and
      without asthma and will be compared in the analyses of ISAAC Phase Two data.

PMID- 17186536
TI  - Four novel single nucleotide polymorphisms within the promoter region of p53 gene
      and their associations with uterine leiomyoma.
AB  - Dysregulated p53 expression has been implicated as a major contributor to
      numerous tumorigenesis. Single nucleotide polymorphisms (SNPs) within the
      functional consequence of the novel p53 promoter region remains obscure. Herein,
      we aimed to establish the extent of genetic variability within the promoter
      region of p53 gene as well as their association with leiomyoma susceptibility.
      Women were divided into two groups, leiomyoma (n = 160) and nonleiomyoma controls
      (n = 200). Total DNA was isolated from the peripheral blood of subjects. The DNA
      fragment containing p53 promoter regions (+64 approximately -404 bp) were
      obtained by amplification of polymerase chain reaction. The variations of DNA
      fragments were detected by DNA sequencing or restriction fragment length
      polymorphism (RFLP). Sequence alignment was used to identify sequence variations
      in p53 promoter regions. Genotypes were analyzed by method of RFLP.
      Genotypes/allelic frequencies in the leiomyoma and control groups were compared.
      A total of 15 sequence variations within p53 promoter region were identified,
      including -408 T/C, -382 A/G, -359 A/G, -325 T/C, -250 A/G, -216 T/C, -205 G/A, 
      198 G/A, -177 T/C, -103 A/G, -81 G/A, -71 G/A, -51 T/A, -33 A/G, and -17 T/C.
      Among these variations, four SNPs (-250 A/G, -216 T/C, -103 A/G, and -33 A/G)
      were established. Allele frequencies of -250*G/-216*C/-103*G/-33*G in the
      leiomyoma group and control group 6.9/5.0/5.9/3.8% and 3.8/1.8/2.3/4.0%,
      respectively. Two of them (-216*C and -103*G) are associated with higher
      leiomyoma susceptibility. We concluded that some sequence variations were
      observed within the promoter region of p53 gene. The SNPs of -216*C and -103*G
      among the identical sequence variations are associated with leiomyoma
      development.

PMID- 17186537
TI  - Angiotensin I-converting enzyme insertion-related genotypes and allele are
      associated with higher susceptibility of endometriosis and leiomyoma.
AB  - Endometriosis and leiomyoma display features similar to malignancy, requiring
      neovascularization to proliferation and growth. Altered vascular-related genes
      might be related to the development of endometriosis and leiomyoma. Polymorphisms
      of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genes have
      been linked with some vascular diseases. This study investigates whether ACE I/D
      gene polymorphisms could be used as markers of susceptibility in endometriosis
      and leiomyoma. Women were divided into three groups: (1) endometriosis (n = 125);
      (2) leiomyoma (n = 120); (3) normal controls (n = 128). Genomic DNA was obtained
      from peripheral leukocyte. ACE I/D gene polymorphisms in intron 16 were amplified
      by polymerase chain reaction and restriction fragment length polymorphism (PCR
      RFLP) Genotypes and allelic frequencies in both groups were compared. We observed
      the genotype distribution and allele frequency of ACE I/D gene polymorphisms in
      both groups were significantly different. Proportions of ACE*I
      homozygote/heterozygote/D homozygote in both groups were: (1) 50.4/24/25.6%; (2)
      25/23.33/51.67%; (3) 10.2/29.7/60.1%. Proportions of I/D alleles in each group
      were: (1) 62.4/37.6%; (2) 36.7/63.3%; (3) 25/75%. We concluded that ACE*I/D gene
      polymorphisms are associated with endometriosis and leiomyoma susceptibilities.
      ACE*I-related genotypes and allele are strongly related to the occurrence of
      endometriosis and moderately related to the occurrence of leiomyoma.

PMID- 17186538
TI  - A vasa-like gene in the giant freshwater prawn, Macrobrachium rosenbergii.
AB  - A molecular marker for germ cells of the giant freshwater prawn, Macrobrachium
      rosenbergii, was studied. A vasa-like gene, Mrvlg, from the ovary was isolated
      and characterized by a reverse transcriptase-polymerase chain reaction (RT-PCR)
      method. A full-length sequence was obtained by the rapid amplification of cDNA
      end (RACE) method. Analysis of the nucleotide sequence revealed that Mrvlg
      comprises 2,686 bps with an open reading frame of 2,130 bps encoding 710 amino
      acids. The deduced amino acid sequence contains four arginine-glycine-glycine
      motifs and eight conserved motifs belonging to the DEAD-box protein family. The
      MrVLG sequence shows high similarity to Vasa homologue of zebrafish (73%). In the
      adult tissues, the Mrvlg transcripts were specifically detected in the germ
      cells. In situ hybridization analysis showed that Mrvlg RNA was detected in the
      cytoplasm of oogonia, previtellogenic, and vitellogenic oocytes and was also
      detected in the nucleoplasm of mature oocytes. In the testis, the Mrvlg
      transcript was detected in the cytoplasm of spermatogonia and primary
      spermatocytes but was detected in the nuclei of secondary spermatocytes and
      sperm. Sequence similarity and specific localization in the germ cells suggest
      that Mrvlg is the prawn vasa homologue of the Drosophila gene and can be used as
      a molecular marker for prawn germ cells.

PMID- 17186539
TI  - The Twenty-First Aspen Cancer Conference: Mechanisms of Toxicity, Carcinogenesis,
      Cancer Prevention, and Cancer Therapy, 2006.

PMID- 17186540
TI  - Connexin 32 potentiates vinblastine-induced cytotoxicity in renal cell carcinoma
      cells.
AB  - We have reported that connexin (Cx) 32 gene, a member of gap junction protein
      family, acts as a tumor suppressor gene in human renal cell carcinoma (RCC). Of
      solid tumors, RCC is one of the most chemoresistant cancers, and there is no
      effective cancer chemotherapy against RCC at present. In this study, we examined
      if the combination of Cx32-dependent tumor-suppressive effect and vinblastine
      (VBL), a chemotherapeutic agent which has been utilized for clinical RCC
      treatment, could be effective in enhancing the sensitivity of RCC to VBL
      treatment. Cx32 expression in a human metastatic RCC cell (Caki-1 cell)
      significantly enhanced in vitro and in vivo VBL-induced cytotoxicity on the cell.
      Cx32 expression in the RCC cells potentiated VBL-induced apoptosis compared to
      the Cx32-negative RCC cells in vitro as well as in vivo. The enhancing apoptosis
      in the RCC cells by Cx32 mainly depended on the decrease of P-glycoprotein (P
      gp), a multidrug resistance gene-1 (MDR-1) product responsible for reduction of
      VBL accumulation into the cells. We also observed that silencing of Cx32 by short
      interfering RNA (siRNA) treatment elevated the level of P-gp in Caki-1 cells and
      that inhibition of P-gp function enhanced VBL-induced apoptosis in the RCC cells.
      These results suggest that Cx32 is effective to enhance VBL-induced cytotoxicity
      in Caki-1 cells via the reduction of P-gp. Overall, it seems that the combination
      of Cx32-dependent tumor-suppressive effect and VBL is promising as a new cancer
      therapy against RCC.

PMID- 17186541
TI  - The presence of BRAF point mutation in adult papillary thyroid carcinomas from
      atomic bomb survivors correlates with radiation dose.
AB  - In papillary thyroid carcinogenesis, the constitutively activated mitogen
      activated protein (MAP) kinase signaling pathway caused by a genetic alteration
      such as RET/PTC rearrangement or mutation of RAS and BRAF genes, is thought to be
      a major early event. Among these, the recently identified BRAF(V600E) mutation
      has been found at high frequency in adult patients with papillary thyroid
      carcinoma (PTC). However, the association between this mutation and radiation
      exposure in adult PTC is still unknown. In this study, we examined the
      BRAF(V600E) mutation in 64 PTCs among adult atomic bomb survivors in Hiroshima,
      Japan, comprising 17 nonexposed (0 mGy) and 47 exposed patients who developed the
      carcinoma after the bombing, and assessed the association of BRAF(V600E) mutation
      with clinico-pathological and epidemiological variables. The median radiation
      dose in PTCs with the BRAF(V600E) mutation was significantly lower than that
      without the mutation (18.5 vs.156.9 mGy, Wilcoxon rank-sum test, P=0.022). A
      significant difference was found in the median latency period (years elapsed from
      atomic bombing to diagnosis) between exposed patients with and without
      BRAF(V600E) mutation (29 vs. 21 yr, Wilcoxon rank-sum test, P=0.014). These
      findings were further confirmed by logistic regression analysis with BRAF(V600E)
      mutation status as a dependent variable and taking into account possible
      interactions between the variables. We found that the log-transformed radiation
      dose and latency period were independently associated with the BRAF(V600E)
      mutation (P=0.039 and P=0.010, respectively). These results suggest that
      involvement of BRAF mutation in thyroid carcinogenesis in exposed people may
      differ from that in the nonexposed people.

PMID- 17186542
TI  - Elevated urokinase-specific surface receptor expression is maintained through its
      interaction with urokinase plasminogen activator.
AB  - Urokinase plasminogen activator (uPA) and its receptor (uPAR) are overexpressed
      in various neoplasms, and play a key role in tumor progression and metastasis. In
      this study, we examined uPA and uPAR expression in a variety of human breast
      cancer cell lines and found that lines with elevated uPA expression also
      exhibited high uPAR expression, suggesting the possibility that uPA and uPAR are
      regulated in concert. To test this possibility, we introduced antisense uPA RNA
      and antisense uPAR RNA in MDA-MB-231 and BT-549 lines that express high levels of
      uPA and uPAR. Antisense uPA RNA not only downregulated uPA expression, but also
      greatly reduced uPAR expression in both lines. However, antisense uPAR RNA
      reduced uPAR expression with no apparent inhibitory effect on the levels of uPA.
      These results indicate that expression of uPAR requires uPA but not vice versa.
      With a panel of uPA and uPAR monoclonal antibodies (mAbs), we observed that the
      mAbs disrupting uPA and uPAR interaction, rather than mAb inhibiting uPA protease
      activity, reduced uPAR expression. Moreover, adding soluble single chain uPA
      (scuPA) to MDA-MB-231 or BT-549 cells expressing antisense uPA mRNA-restored uPAR
      expression. These findings suggest that uPA dictates uPAR expression and that uPA
      binding to uPAR transmits signals for uPAR expression. Finally, we provided
      evidence that Fyn, a Src family kinase, is involved in uPA-induced uPAR
      expression.

PMID- 17186543
TI  - Growth arrest-specific gene 6 and Axl signaling enhances gastric cancer cell
      survival via Akt pathway.
AB  - Activation of tyrosine kinases is an important factor during cancer development.
      Axl, one of the receptor tyrosine kinases, binds to the specific ligand growth
      arrest-specific gene 6 (Gas6), which encodes a vitamin K-dependent gamma
      carboxyglutamyl protein. Although many receptor tyrosine kinases and their
      ligands are involved in gastric carcinogenesis, whether Gas6-Axl signaling is
      involved in gastric carcinogenesis has not been elucidated. The aim of this study
      was to investigate the expression of Gas6 and Axl in gastric cancer and also
      their roles during gastric carcinogenesis. mRNA and protein of Gas6 and Axl were
      highly expressed in a substantial proportion of human gastric cancer tissue and
      cell lines, and Gas6 expression was significantly associated with lymph node
      metastasis. With recombinant Gas6 and a decoy-receptor of Axl in vitro, we
      demonstrated that Gas6-Axl signaling pathway enhanced cellular survival and
      invasion and suppressed apoptosis via Akt pathway. Our results suggests that Gas6
      Axl signaling plays a role during gastric carcinogenesis, and that targeting Gas6
      Axl signaling could be a novel therapeutic for gastric cancer.

PMID- 17186544
TI  - Massive hemoptysis in an 11-year-old girl with isolated pulmonary arteritis.
AB  - A 10-year-old girl developed recurrent bouts of massive hemoptysis over a 9-month
      period. No obvious bleeding source was detected. Her pulmonary angiogram showed a
      pulmonary aneurysm of the second branch of the left main pulmonary artery as well
      as widespread irregularities of the pulmonary arteries including areas of
      stenosis and pruning. Elective embolization of the aneurysm did not control
      hemoptysis and emergency left upper lobectomy had to be performed. Histology
      showed large artery wall injury with acute leucocytoclastic inflammation,
      fibrinoid necrosis, granulomatous inflammation, and ectasia of vessel wall. This
      combination of abnormalities has not been described to date and represents the
      first case of isolated pulmonary arteritis in children prior to puberty.

PMID- 17186545
TI  - Reference values for sleep-related respiratory variables in asymptomatic European
      children and adolescents.
AB  - AIM: Only a limited number of studies, designed to establish normal values for
      sleep-related respiratory variables in children, have been reported, and all are
      non-European. The aim of this study was to expand the knowledge on normative data
      in children. METHODS: Subjects ranging from 6 to 16 years were recruited and
      underwent full polysomnography. Only subjects without sleep disordered breathing
      or other sleep problems as assessed by clinical history were included. RESULTS:
      Sixty subjects were studied (<age> = 11.7 +/- 2.6 years; 28 boys; <relBMI> =
      118.8 +/- 30.6%). <Central apnea index> was 0.85 +/- 1.06 (range: 0.0-5.5).
      <Obstructive apnea index> was 0.06 +/- 0.16 (range: 0.0-0.9); 11 patients had a
      total of 31 obstructive apneas. Only five obstructive hypopneas were detected
      with <obstructive apnea hypopnea index> = 0.08 +/- 0.17 (range: 0.0-0.9).
      <Respiratory disturbance index> was 1.98 +/- 1.39 (range: 0.1-7.2). <SaO2> was
      97.0 +/- 0.6% (range: 96.0-98.0); <SaO2nadir> was 91.8 +/- 2.7% (range: 82.0
      96.0); <% of total sleep time with SaO2 >or= 95%> was 98.7 +/- 2.1% (range: 90.8
      100.0); <oxygen desaturation index> was 0.8 +/- 0.9 (range: 0.0-4.9) and <arousal
      index> was 6.1 +/- 1.8 (range: 2.7-10.9). Snoring was detected in 15 patients (4
      overweight subjects), with no difference in patient characteristics and sleep
      related respiratory variables between snorers and non-snorers. Subjects in the
      overweight group (n = 22) had a lower SaO2nadir (90.8 +/- 2.7 vs. 92.4 +/- 2.6; P
      = 0.01) and a higher ODI (1.3 +/- 1.3 vs. 0.4 +/- 0.4; P = 0.0002) than their
      normal weight peers. CONCLUSION: Our data are in agreement with other non
      European studies, designed to establish normal values in children.

PMID- 17186546
TI  - Peripheral airway involvement in CF and asthma compared by inert gas washout.
AB  - Multiple-breath N2 washouts were performed before and after bronchodilation in 15
      patients with moderately severe asthma (mean age 13 years), and in 11 patients
      with cystic fibrosis (CF; mean age 16 years) matched for FEV1. Eighteen healthy
      subjects (mean age 15 years) were studied before bronchodilation. The lung
      clearance index (LCI) was determined from the washout curve and gas trapping was
      assessed from five subsequent large breaths. Analysis of the progression of the
      concentration normalized phase III slopes (Sn(III)) over the washout was used to
      determine inhomogeneity in the conducting airways (S(cond)) and inhomogeneity
      close to or within the gas exchange zone (S(acin)). Before bronchodilation all
      washout indexes were abnormal in the CF group, and all but S(acin) in the asthma
      group. Two indexes were higher in CF than in asthma: LCI (11.5 (3.3) vs. 8.7
      (1.3); P < 0.01), and S(acin) (0.307 (0.207) vs. 0.142 (0.071); P < 0.01), while
      gas trapping indexes and S(cond) (0.151 (0.071) vs. 0.127 (0.041)) did not differ
      significantly. After bronchodilation, all indexes improved in asthma and only
      S(cond) remained abnormally elevated. In CF, only a modest but statistically
      significant S(acin) improvement was seen and all indexes stayed abnormal. The
      study shows that overall ventilation inhomogeneity and particularly inhomogeneity
      in or close to the gas exchange zone are more pronounced in CF than in asthma
      matched for FEV1, while inhomogeneity in the conducting airway zone is similar.
      After bronchodilation, residual abnormalities of airway function are seen all
      through the airway tree in CF but only in the conducting airways in asthma.

PMID- 17186547
TI  - Beneficial effects of dithiothreitol on relative levels of glutathione S
      transferase activity and thiols in oocytes, and cell number, DNA fragmentation
      and allocation at the blastocyst stage in the mouse.
AB  - We analyzed the effect of in vitro aging of mouse oocytes in the presence of
      dithiothreitol (DTT) on relative levels of glutathione S-transferase (GST)
      activity and thiols in oocytes, and cell number, DNA fragmentation and cellular
      allocation to the inner cell mass (ICM) and trophectoderm (TE) lineage at the
      blastocyst stage. Ovulated oocytes from gonadotropin primed hybrid female mice of
      6-8 weeks of age were aged in vitro in the presence of 0, 5, 50, or 500 microM
      DTT for 6 hr prior to insemination. Relative levels of GST activity and thiols in
      oocytes were determined by confocal laser scanning microscopy, DNA fragmentation
      using a single-step TUNEL method, and cell allocation to the ICM and TE lineage
      by blastocyst staining with propidium iodide and Hoechst 33258. Non-aged oocytes
      exhibited higher relative levels of GST activity and thiols when compared to
      oocytes aged in the presence of 0, 5, and 50 microM DTT. Day 5 blastocysts from
      the 5, 50, and 500 microM DTT groups exhibited higher total number of cells,
      number of ICM cells, and ICM/TE ratio, but lower percentage of number of nuclei
      with DNA fragmentation/number of ICM cells than blastocyst from the 0 microM DTT
      group. These data show that DTT counteracts the negative effects of a post
      ovulatory aging of mouse oocytes in vitro on relative levels of GST activity and
      thiols in oocytes, and percentage of number of nuclei with DNA
      fragmentation/number of ICM cells, total number of cells, number of ICM cells and
      ICM/TE ratio in Day 5 blastocysts.

PMID- 17186548
TI  - Pinocembrin triggers Bax-dependent mitochondrial apoptosis in colon cancer cells.
AB  - Bioflavanoids are the major pigments in plants with multitude of biological
      activities including inhibition of proliferation or induction of apoptosis in
      tumor cells. Even though the safety records of most flavanoids are exceptional,
      its therapeutic use is still in its infancy. We have isolated pinocembrin (5,7
      dihydroxyflavanone) from Alpinia galanga that showed cytotoxicity against a
      variety of cancer cells including normal lung fibroblasts with relative
      nontoxicity to human umbilical cord endothelial cells. The compound induced loss
      of mitochondrial membrane potential with subsequent release of cytochrome c and
      processing of caspase-9 and -3 in colon cancer cell line HCT 116. Processing of
      caspase-8 was minimal. The initial trigger for mitochondrial apoptosis appears to
      be by the translocation of cytosolic Bax protein to mitochondria. Overexpression
      of proapoptotic Bax protein sensitized the colon cancer cells to pinocembrin
      induced apoptosis and Bax knockout cells were resistant to pinocembrin-induced
      apoptosis. Antiapoptotic protein Bcl-X(L) only partially prevented apoptosis
      induced by this compound. The Bax-dependent cell death involving classical
      cytochrome c release and processing of caspase-9 and -3 suggests that pinocembrin
      is a classical mitochondrial apoptosis inducer. But the failure of Bcl-X(L)
      overexpression to completely prevent apoptosis induced by this compound suggests
      that pinocembrin is capable of triggering mitochondrial-independent cell death
      that needs to be clarified. The existence of cell death upon Bcl-X(L)
      overexpression is a promising feature of this compound that can be exploited
      against drug resistant forms of cancer cells either alone or in combination with
      other drugs.

PMID- 17186549
TI  - Engineering zinc finger protein transcription factors to downregulate the
      epithelial glycoprotein-2 promoter as a novel anti-cancer treatment.
AB  - Zinc finger protein transcription factors (ZFP-TFs) are emerging as powerful
      novel tools for the treatment of many different diseases. ZFPs are DNA-binding
      motifs and consist of modular zinc finger domains. Each domain can be engineered
      to recognize a specific DNA triplet, and stitching six domains together results
      in the recognition of a gene-specific sequence. Inhibition of gene expression can
      be achieved by fusing a repressor domain to these DNA-binding motifs. In this
      study, we engineered ZFP-TFs to downregulate the activity of the epithelial
      glycoprotein-2 (EGP-2) promoter. The protein EGP-2 is overexpressed in a wide
      variety of cancer types and EGP-2 downregulation has been shown to result in a
      decreased oncogenic potential of tumor cells. Therefore, downregulation of EGP-2
      expression by ZFP-TFs provides a novel anti-cancer therapeutic. Using a
      straightforward strategy, we engineered a 3-ZFP that could bind a 9 bp sequence
      within the EGP-2 promoter. After the addition of a repressor domain, this 3-ZFP
      TF could efficiently downregulate EGP-2 promoter activity by 60%. To demonstrate
      the flexibility of this technology, we coupled an activation domain to the
      engineered ZFP, resulting in a nearly 200% increase in EGP-2 promoter activity.
      To inhibit the endogenous EGP-2 promoter, we engineered 6-ZFP-TFs. Although none
      of the constructed ZFP-TFs could convincingly modulate the endogenous promoter,
      efficient and specific inhibition of the exogenous promoter was observed.
      Overall, ZFP-TFs are versatile bi-directional modulators of gene expression and
      downregulation of EGP-2 promoter activity using ZFP-TFs can ultimately result in
      a novel anti-cancer treatment.

PMID- 17186550
TI  - Role of IKK and oscillatory NFkappaB kinetics in MMP-9 gene expression and
      chemoresistance to 5-fluorouracil in RKO colorectal cancer cells.
AB  - Nuclear factor kappa B (NFkappaB) is a central participant in the metastasis and
      chemoresistance of colorectal cancer (CRC). However, it is not fully understood
      to what extent NFkappaB contributes to induction of the metastasis-associated
      matrix metalloprotease-9 (MMP-9) gene and sensitivity to the commonly used
      chemotherapeutic 5-fluorouracil (5-Fu) in CRC. Using the RKO human CRC cell line
      and two NFkappaB signaling deficient RKO mutants, we investigated NFkappaB's role
      in the induction of MMP-9 and 5-Fu sensitivity in RKO CRC cells. NFkappaB plays a
      predominant role in MMP-9 gene induction in RKO cells, as evidenced by the
      failure of tumor necrosis factor alpha (TNFalpha) to induce MMP-9 in either of
      the NFkappaB signaling mutants. RKO cells exhibit a robust, oscillatory NFkappaB
      activity in response to TNFalpha not seen in either of the NFkappaB mutant cell
      lines, which instead demonstrate diminished, nonoscillatory NFkappaB activation.
      Analysis of TNFalpha-induced phosphorylation and MMP-9 promoter recruitment of
      the p65 NFkappaB subunit revealed a significant reduction in p65 phosphorylation
      as well as reduced and altered recruitment of p65 to the MMP-9 gene promoter in
      the mutants compared to the parental RKO cell line. 5-Fu only activated NFkappaB
      in the parental RKO cells through induction of IkappaB-kinase (IKK) activity and
      increased sensitivity to 5-Fu is observed in both NFkappaB mutant lines. Our
      results suggest that TNFalpha-dependent induction of MMP-9 gene expression is
      tightly regulated by oscillatory/cumulative activation of NFkappaB and that 5-Fu
      stimulates NFkappaB and RKO CRC cell survival through induction of IKK activity.

PMID- 17186551
TI  - Modulation of UVB-induced and basal cyclooxygenase-2 (COX-2) expression by
      apigenin in mouse keratinocytes: role of USF transcription factors.
AB  - Apigenin is a bioflavonoid with chemopreventive activity against UV- or
      chemically-induced mouse skin tumors. To further explore the mechanism of
      apigenin's chemopreventive activity, we determined whether apigenin inhibited UVB
      mediated induction of cyclooxygenase-2 (COX-2) expression in mouse and human
      keratinocytes. Apigenin suppressed the UVB-induced increase in COX-2 protein and
      mRNA in mouse and human keratinocyte cell lines. UVB radiation of keratinocytes
      transfected with a mouse COX-2 promoter/luciferase reporter plasmid resulted in a
      threefold increase in transcription from the promoter, and apigenin inhibited the
      UV-induced promoter activity at doses of 5-50 microM. Transient transfections
      with COX-2 promoter deletion constructs and COX-2 promoter constructs containing
      mutations in specific enhancer elements indicated that the effects of UVB
      required intact Ebox and ATF/CRE response elements. Electrophoretic mobility
      shift assays with supershifting antibodies were used to identify USF-1, USF-2,
      and CREB as proteins binding to the ATF/CRE-Ebox responsive element of the COX-2
      promoter. Keratinocytes co-transfected with the COX-2 luciferase reporter and a
      USF-2 expression vector, alone or in combination with a USF-1 expression vector,
      exhibited enhanced promoter activity in both UVB-irradiated and nonirradiated
      cultures. However, COX-2 promoter activity was inhibited in keratinocytes co
      transfected with USF-1 alone. Finally, we present data showing that the
      suppressive effect of apigenin on COX-2 expression could be reversed by co
      expression of USF-1 and USF-2. These results suggest that one pathway by which
      apigenin inhibits COX-2 expression is through modulation of USF transcriptional
      activity.

PMID- 17186552
TI  - Requirement for, and patterns of, pyruvate and glutamine metabolism in the
      domestic dog oocyte in vitro.
AB  - Supplementation of energy substrates to culture medium is essential for
      resumption and completion of meiosis in vitro for many mammalian species.
      Objectives were to study the dog oocyte, specifically the influences of pyruvate
      and glutamine on maturation and the utilization of these two substrates at
      various developmental stages and incubation times. Ovarian oocytes (n=681) were
      obtained from spayed bitches and cultured for 48 hr in TCM 199 medium containing
      various concentrations of pyruvate (0-2.5 mM) and glutamine (0-4 mM) before being
      assessed for nuclear status. For analyzing metabolic activity, 259 dog oocytes
      were cultured for 0, 12, 24, 36, or 48 hr, assessed for pyruvate and glutamine
      metabolism using the hanging drop method and then evaluated for nuclear status.
      Neither pyruvate nor glutamine had influence (P > 0.05) on oocyte maturation in
      vitro (IVM). However, both culture interval and meiotic status influenced
      pyruvate uptake (P < 0.05). Specifically, pyruvate uptake declined as the oocyte
      progressed from the germinal vesicle (GV) to metaphase II (MII) stage. Glutamine
      oxidation decreased as culture duration progressed (P < 0.05). In summary,
      pyruvate or glutamine is not required to promote successful IVM of dog oocytes.
      But, both substrates are being metabolized, and in patterns different to the
      domestic cat, another carnivore species. Pyruvate played an important role
      earlier in the maturational process, and less glutamine was oxidized as the
      oocyte neared nuclear maturation. These variations emphasize the importance of
      defining species specificities in carnivores before expecting consistently
      successful IVM/IVF.

PMID- 17186553
TI  - Impact of cryopreservation and reactive oxygen species on DNA integrity, lipid
      peroxidation, and functional parameters in ram sperm.
AB  - Assisted reproduction using frozen-thawed semen has practical advantages,
      although cryopreservation is detrimental to sperm fertility in most mammals. We
      examined the influence of cryopreservation and reactive oxygen species (ROS) on
      ram sperm DNA stability (using SCSA), lipid peroxidation (LPO), chlortetracycline
      fluorescence (CTC) patterns, motility and viability. In Experiment 1, DNA
      integrity, LPO, CTC, motility and viability tests were performed on fresh and
      cryopreserved sperm after 0, 6, and 24 hr in synthetic oviductal fluid (SOF). In
      Experiment 2, fresh sperm were incubated in serum-free SOF (SOF-S; 1, 4, and 24
      hr) with 0, 50, 150, or 300 microM H2O2 then assayed. Cryopreservation increased
      the percentage of sperm with a high DNA fragmentation index (%DFI), decreased the
      percentages of motile and viable sperm at thawing (0 hr), but did not affect LPO.
      H2O2 (150 or 300 microM) increased %DFI after 24 hr. LPO or sperm viability were
      not affected by H2O2, although most motility parameters decreased. H2O2 decreased
      the percentage of chlortetracycline pattern F sperm at 4 hr and increased the
      percentage of acrosome-reacted sperm (pattern AR) after 1 hr. Pooled data of
      Experiment 2 showed LPO was positively correlated with SCSA (r = 0.29 to r =
      0.59; P < 0.05 to P < 0.01), while most motility parameters and the percentage of
      viable sperm were negatively correlated with LPO (r = -0.30 to r = -0.38; P <
      0.05 to P < 0.01). LPO was positively correlated with the percentage of pattern
      AR sperm (r = 0.33; P < 0.01). Cryopreservation and H2O2 promote DNA instability
      in ram sperm, though motility is a more sensitive indicator of oxidative stress
      than the other parameters investigated.

PMID- 17186554
TI  - The PLAC1 protein localizes to membranous compartments in the apical region of
      the syncytiotrophoblast.
AB  - PLAC1 is a trophoblast-specific gene that maps to a locus on the X-chromosome
      important to placental development. We have previously shown that PLAC1 gene
      expression is linked to trophoblast differentiation. The objective of this study
      was to define the localization of the PLAC1 polypeptide as a prerequisite to
      understanding its function. Polyclonal antibodies specific for the putative PLAC1
      polypeptide were generated. The subcellular localization of PLAC1 in the
      trophoblast was examined by immunohistochemical analysis of human placenta
      complemented by immunoblot analysis of subcellular fractions. Brightfield
      immunohistochemical analysis of placental tissue indicated that the PLAC1 protein
      localizes to the differentiated syncytiotrophoblast in the apical region of the
      cell. Deconvlution immunofluorescence microscopy confirmed localization to the
      apical region of the syncytiotrophoblast. Its distribution included both
      intracellular compartments as well as loci in close association with the maternal
      facing, microvillous brush border membrane (MVM). These findings were supported
      by immunoblot analysis of subcellular fractions. A 30 kDa band was associated
      with the microsomal fraction of placental lysates but not the mitochondrial,
      nuclear, or soluble fractions, suggesting PLAC1 is targeted to a membrane
      location. Plasma membranes were obtained from the fetal-facing, basal surface
      (BM) and the maternal-facing, MVM of the syncytiotrophoblast membrane. PLAC1
      immunoreactivity was only detected in membrane fractions derived from the apical
      MVM consistent with immunohistochemical analyses. These data demonstrate that the
      PLAC1 protein is restricted primarily to the differentiated trophoblast,
      localizing to intracellular membranous compartment(s) in the apical region of the
      syncytiotrophoblast and associated with its apical, microvillous membrane
      surface.

PMID- 17186555
TI  - Enhancement of relaxivity rates of Gd-DTPA complexes by intercalation into
      layered double hydroxide nanoparticles.
AB  - In this paper we report the preparation and characterization of [Gd(dtpa)](2-)
      intercalated layered double hydroxide (LDH) nanomaterials. [Gd(dtpa)](2-)
      (gadolinium(III) diethylene triamine pentaacetate) was transferred into LDH by
      anionic exchange. The intercalation of [Gd(dtpa)](2-) into LDH was confirmed by X
      ray diffraction for the new phase with the interlayer spacing of 3.5-4.0 nm and
      by FTIR for the characteristic vibration peaks of [Gd(dtpa)](2-). The morphology
      of the nanoparticles was influenced by the extent of [Gd(dtpa)](2-) loading, in
      which the poly-dispersity quality decreased as the [Gd(dtpa)](2-) loading was
      increased. Compared with the morphology of the original Mg(2)Al-Cl-LDH
      nanoparticles (hexagonal plate-like sheets of 50-200 nm), the modified LDH
      Gd(dtpa) nanoparticles are bar-like with a width of 30-60 nm and a length of 50
      150 nm. LDH-Gd(dtpa) was expected to have an increased water proton magnetic
      resonance relaxivity due to the intercalation of [Gd(dtpa)](2-) into the LDH
      interlayer that led to slower molecular anisotropic tumbling compared with free
      [Gd(dtpa)](2-) in solution. Indeed, LDH-nanoparticle suspension containing
      approximately 1.6 mM [Gd(dtpa)](2-) exhibits a longitudinal proton relaxivity
      r(1) of approximately 16 mM(-1) s(-1) and a transverse proton relaxivity r(2) of
      approximately 50 mM(-1) s(-1) at room temperature and a magnetic field of 190
      MHz, which represents an enhancement four times (r(1)) and 12 times (r(2)) that
      of free [Gd(dtpa)](2-) in solution under the same reaction conditions. We have
      thus tailored LDH-nanoparticles into a novel contrast agent with strong
      relaxivity, promising for great potential applications in magnetic resonance
      imaging.

PMID- 17186556
TI  - Layer frustration, polar order and chirality in liquid crystalline phases of
      silyl-terminated achiral bent-core molecules.
AB  - A novel class of bent-core molecules with oligo(siloxane) or carbosilane units at
      both ends was synthesized and the self-organization of these molecules was
      investigated by polarizing microscopy, DSC, X-ray scattering, dielectric and
      electrooptical methods. Depending on the size of the silicon-containing segments,
      smectic and columnar liquid crystalline phases are formed. Most smectic phases
      are low birefringent and composed of macroscopic domains of opposite handedness
      (dark conglomerate phases). The switching process in these smectic phases is
      surface stabilized ferroelectric and, depending on the conditions, two distinct
      slow relaxation processes to nonpolar structures were observed. It is proposed
      that the smectic phases are built up by chiral and polar SmCsPF layer stacks
      which are separated by anticlinic interfaces. If the size of these layer stacks
      is sufficiently large a coupling to the substrate surfaces takes place and
      ferroelectric switching is observed. It is also suggested that the sponge-like
      layer distortion, occurring in the low birefringent mesophases, is due to an
      escape from the local polar order within these SmCsPF layer stacks. For compounds
      with larger silylated units a steric frustration arises, which leads to layer
      modulation (columnar ribbon phases) and this is associated with a transition from
      ferroelectric to antiferroelectric switching. All compounds show a switching of
      the molecules around the long axis which reverses the layer chirality.

PMID- 17186557
TI  - A highly regular hexapod structure of lead sulfide: solution synthesis and Raman
      spectroscopy.
AB  - A highly regular hexapod-like structure of PbS with six symmetric arms has been
      synthesized by a simple and mild chemical solution route. The hexapod-like PbS
      structure was characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and high-resolution TEM
      (HRTEM). The results show that each arm is perpendicular to the other four, and
      opposite to the last one. The arms are about 0.3-0.6 microm long, which have
      about 40-60 nm tips and 150-200 nm base. And the arm shows an icicle-like
      structure and some clear steps, and grows along 100 directions. The most possible
      growth mechanism discussed herein is based on the characterization results. The
      Raman spectra of the hexapod-like PbS structure were investigated. The results
      show that our products are sensitive to the laser and can be photodegraded
      easily.

PMID- 17186558
TI  - Oligothiophene-linked bisnaphthopyrans: sequential and temperature-dependent
      photochromism.
AB  - Photochromic bisnaphthopyrans linked with oligothiophenes were synthesized and
      their photochromic behavior studied. Sequential and temperature-dependent
      photochromism was observed in the oligothiophene linked bisnaphthopyrans. The
      kinetics of photo and thermal processes in bisnaphthopyrans in comparison with
      naphthopyrans were studied. Substituent and linking effects on the photochromic
      properties are discussed. We demonstrate that the cross-talk between the two
      photochromophores is dependent on the length of the oligothiophene linker. The
      presence of the bithiophene linker led to high colorability and high quantum
      yield of coloration.

PMID- 17186559
TI  - Molecular tectonics of metal-organic frameworks (MOFs): a rational design
      strategy for unusual mixed-connected network topologies.
AB  - To systematically explore the higher-dimensional network structures with mixed
      connectivity, a series of two-dimensional (2D) and three-dimensional (3D) metal
      organic frameworks (MOFs) with unusual (3,6)-connected net topologies are
      presented. These crystalline materials include [{[Mn(btza)2(H2O)2].2 H2O}n] (1),
      [{[Zn(btza)2(H2O)2].2 H2O}n] (2), [{[Cu(btza)2].H2O}n] (3), and [{[Cd(btza)2].3
      H2O}n] (4), which have been successfully assembled through a predesigned three
      connected organic component bis(1,2,4-triazol-1-yl)acetate (btza) with a variety
      of octahedral metal cores based on the modular synthetic methodology. The
      topological paradigms shown in this work cover the 2D CdCl2, 3D
      (4(2).6)2(4(4).6(2).8(7).10(2)), and pyrite (pyr) types. That is, when properly
      treated with the familiar first-row divalent metal ions, btza may perfectly
      furnish the coordination spheres for effective connectivity to result in diverse
      (3,6)-connected nets. Beyond this, a detailed analysis of network topology for
      all known 3D (3,6)-connected frameworks in both inorganic and inorganic-organic
      hybrid materials is described. Specific network connectivity of these MOFs
      indicates that the metal centers represent the most significant and alterable
      factor in structural assembly, although they show reliable and similar
      geometries. In this context, the combination of the distinct d10 AgI ion with
      btza in different solvents affords two isomorphous MOFs [{[Ag(btza)].glycol}n]
      (5) and [{[Ag(btza)]CH3OH}n] (6) with a binodal 4-connected 3D SrAl2 (sra)
      topology. The network structures of MOFs 1-3 and 5 turn out to be more
      complicated and interesting if one considers the hydrogen bonding between the
      host coordination frameworks and the intercalated solvent molecules. Furthermore,
      the role of the included solvents in the generation and stabilization of MOFs 1-6
      is also investigated.

PMID- 17186560
TI  - Pt(0) and Pd(0) olefin complexes of the metalloid N-heterocyclic carbene
      analogues [E(I)(ddp)] (ddp=2-{(2,6-diisopropylphenyl)amino}-4-{(2,6
      diisopropylphenyl)imino}-2-pentene; E=Al, Ga): ligand substitution, H--H and Si-
      H bond activation, and cluster formation.
AB  - Various products of the reaction of [E(ddp)] (ddp=2-{(2,6
      diisopropylphenyl)amino}-4-{(2,6-diisopropylphenyl)imino}-2-pentene; E=Al, Ga)
      with Pt(0) and Pd(0) olefin complexes are reported. Thus, the reaction of
      [Pt(cod)(2)] (cod=1,5-cyclooctadiene) with two equivalents of [Ga(ddp)] yields
      [Pt(1,3-cod){Ga(ddp)}(2)] (1), whereas treatment of [Pd(2)(dvds)(3)]
      (dvds=1,1,3,3-tetramethyl1,3-divinyldisiloxane) with [E(ddp)] leads to the
      monomeric compounds [(dvds)Pd{E(ddp)}] (E=Ga (2 a), Al (2 b)) by substitution of
      the bridging dvds ligand. Both 1 and 2 a readily react with strong pi-acceptor
      ligands such as CO or tBuNC to give the dimeric compounds [M{mu(2)-Ga(ddp)}(L)]
      (L=CO, tBuNC; M=Pt (3 a, 5 a), Pd (3 b, 5 b)), respectively. Based on (1)H NMR
      spectroscopic data, [Pt{Ga(ddp)}(2)(CO)] is likely to be an intermediate in the
      formation of 3 a. Furthermore, reactions of 1 with H(2) and HSiEt(3) yield the
      monomeric compounds [Pt{Ga(ddp)}(2)(H)(2)] (7) and [Pt{Ga(ddp)}(2)(H)(SiEt(3))]
      (8). Finally, the reaction of [Pt(cod)(2)] with one equivalent of [Ga(ddp)] in
      the presence of H(2) in hexane gives the new dimeric cluster [Pt{mu(2)
      Ga(ddp)}(H)(2)](2) (9).

PMID- 17186561
TI  - Dimethylzinc-mediated, enantioselective synthesis of propargylic amines.
AB  - A one-pot, enantioselective synthesis of N-aryl propargylic amines, using
      alkynylation reagents obtained from dimethylzinc and terminal acetylenes in
      combination with various aldehydes and o-methoxyaniline as starting materials,
      has been developed. Enantiopure beta-amino alcohols derived from norephedrine
      were used as non-covalent chiral auxiliaries, both in stoichiometric or
      substoichiometric amount. After optimization, propargylic amines were obtained in
      good to high yields (up to 93%) and with moderate to high enantiomeric excesses
      (up to 97% ee). The possibility to recover the chiral auxiliary after the
      reaction was demonstrated.

PMID- 17186562
TI  - Efficient iron/copper co-catalyzed arylation of nitrogen nucleophiles.

PMID- 17186563
TI  - Ultrasonographic measurement of fetal nasal bone length in the second trimester
      in Korean population.
AB  - OBJECTIVE: To establish the reference range of fetal nasal bone length (NBL) in
      the second trimester in the Korean population and to determine its clinical value
      in screening for trisomy 21. STUDY DESIGN: A total of 3019 consecutive fetuses at
      16-28 weeks of gestation underwent ultrasonographic measurement of NBL at Asan
      Medical Center from October 2003 to August 2005. RESULTS: Fetal profile was
      successfully examined in 95.6% (2885/3019) of the fetuses. NBL increased linearly
      with advanced gestation (R(2) = 0.4337, p < 0.001). During this period, 23
      fetuses with chromosomal abnormalities (including nine with trisomy 21, two with
      trisomy 18, and three with Turner syndrome) were detected. In trisomy 21,
      hypoplastic nasal bone (<2.5th percentile) was seen in 3/9 fetuses, and the NBL
      of one fetus was between the 2.5th and 5th percentile. Hypoplastic nasal bone was
      seen in 3.1% (89/2833) of fetuses with normal chromosomal or postnatal
      examination findings. CONCLUSION: We present the normal range of NBL in the
      second trimester in the Korean population and also their linear relationship with
      gestational age (GA). The NBL appears to be shorter in Korean fetuses than
      Caucasian and Chinese fetuses. This indicates that the normal range would vary
      between races and that a relative percentile is a more reliable screening
      criterion than an absolute value.

PMID- 17186565
TI  - Deep-hidden anastomoses in monochorionic twin placentae are harmless.
AB  - OBJECTIVES: Our objective was to identify the clinical consequences of deep
      hidden anastomoses that occur underneath the placental surface. METHODS: Twelve
      placentae that underwent intrauterine laser ablation of placental anastomoses for
      twin-twin transfusion syndrome (TTTS) and 14 non-TTTS controls were investigated
      for deep-hidden anastomoses. Additionally, we investigated the inter-twin
      haemoglobin differences as an indicator for fetofetal transfusion. Placentae were
      divided into four groups: TTTS placentae without residual chorionic-plate
      anastomoses without deep-hidden anastomoses (group 1) and with deep-hidden
      anastomoses (group 2), and non-TTTS placentae with chorionic-plate anastomoses
      without deep-hidden anastomoses (group 3) and with deep-hidden anastomoses (group
      4). RESULTS: Deep-hidden anastomoses were identified in 58% (7/12) of the TTTS
      placentae after laser surgery and in 64% (9/14) of the non-TTTS placentae. Groups
      1 and 2 had equal inter-twin haemoglobin differences: medians 1.4 and 1.2 gr/dL,
      respectively (p = 0.48). In group 3, the median inter-twin haemoglobin difference
      without deep-hidden anastomoses was 2.6 gr/dL (group 3) and with deep-hidden
      anastomoses (group 4) it was 5.1 gr/dL (p = 0.26). CONCLUSION: Both comparisons
      imply that deep-hidden anastomoses did not cause any additional increase in Hb
      difference. In conclusion, haematological and additional hemodynamical analysis
      show that deep-hidden anastomoses are likely to occur without any clinical
      consequences.

PMID- 17186564
TI  - Three-vessel view of the fetal heart: in utero development of the great vessels.
AB  - OBJECTIVES: The purpose of our study is to provide reference values for the great
      vessels obtained from images of the three-vessel view of the fetal heart, with an
      emphasis on the size discrepancy of the great vessels. METHODS: From February
      2003 to May 2003, the main pulmonary artery (MPA), ascending aorta (AA), and SVC
      were measured in well-dated, nonanomalous fetuses scanned at 14-38 weeks of
      gestation. RESULTS: The size of each great vessel had a significant positive
      relationship with advance in gestation (P < 0.001); MPA (mm) = -2.76 + 0.34 x GA,
      ascending aorta (AA) (mm) = -1.73 + 0.26 x GA - 1.18E - 05 x GA(3), and SVC (mm)
      = 0.33 + 0.01 x GA(2) - 4.12E - 05 x GA(3). The AA/MPA ratio was significantly
      decreased with advance in gestation, while the SVC/AA ratio was significantly
      increased; AA/MPA ratio = -1.24 - 0.03 x GA + 3.88E - 04 x GA(2); P < 0.001,
      SVC/AA ratio = 0.63 - 5.43E - 03 x GA + 1.96E - 04 x GA(2); P < 0.001.
      CONCLUSION: On the three-vessel view of the fetal heart, the interpretation of
      the size discrepancy of the great vessels needs to be adjusted according to fetal
      growth.

PMID- 17186566
TI  - Identification of nucleated red blood cells in maternal circulation: a second
      step in screening for fetal aneuploidies and pregnancy complications.
AB  - BACKGROUND: Identification of fetal nucleated red blood cells (NRBCs) in maternal
      circulation can facilitate non-invasive prenatal diagnosis, but technical
      difficulties still exist. An increase in the number of circulating NRBCs,
      however, could indicate fetal aneuploidies or pregnancy complications. MATERIALS
      AND METHODS: The number of NRBCs was determined from 20 mL peripheral blood in
      351 women in the second trimester of pregnancy after isolation by magnetic cell
      sorting (MACS) with anti-CD71 antibody and identification with May
      Grunwald/Giemsa staining. RESULTS: An average of eight NRBCs (range 1-12) were
      identified among 282 women with chromosomally normal fetuses. In cases known to
      carry aneuploid fetuses the mean number was 35 (range 7-113), but when the fetus
      had trisomy 21 (n = 17) an average of 71 NRBCs were identified. Among 26 carriers
      of beta-thalassemia, 42 NRBCs (range 22-158) were isolated. In pregnancies with
      abnormal Doppler findings in both uterine arteries (n = 20), 15 NRBCs (range 2
      75) were isolated. CONCLUSION: Determining the number of NRBCs in maternal
      circulation could represent an additional screening step for fetal aneuploidies,
      as long as the anemic status of the mother is taken into consideration. However,
      more cases with abnormal Doppler results must be investigated before this test is
      used for in the prediction of pregnancy complications.

PMID- 17186567
TI  - C21ORF105, A chromosome 21-encoded mRNA, is not a discriminative marker gene for
      prediction of Down syndrome in maternal plasma.
AB  - OBJECTIVES: The presence and detectability of placental mRNA in maternal plasma
      opens possibilities for the development of non-invasive prenatal diagnostic
      tests. In this study, we tested C21orf105, a chromosome 21-encoded, placentally
      expressed gene, in maternal plasma of women carrying a fetus with or without
      trisomy 21. METHODS: Using real-time RT-PCR, we determined transcript levels of
      target (C21orf105) and reference (hPL) genes in first-trimester plasma samples.
      Plasma was obtained from first-trimester EDTA blood after two sequential
      centrifugation steps and stored at -70 degrees C. After RNA extraction,
      quantitative RT-PCR was performed using Taqman probes. RESULTS: From the 51
      samples, 43 samples were conclusive. Comparison of transcript levels of C21orf105
      in both groups showed no significant differences. When expressed as ratios of
      hPL/C21orf105, the differences between trisomy 21 and normal pregnancies remained
      non-significant. CONCLUSIONS: The amount of C21orf105 mRNA in maternal plasma,
      although situated in the Down syndrome critical region on chromosome 21 and up
      regulated in trisomy 21 placentas, is not higher in women carrying a fetus with
      trisomy 21.

PMID- 17186568
TI  - The pharmacological properties of anisodamine.
AB  - Anisodamine is a naturally occurring atropine derivative that has been isolated,
      synthesized and characterized by scientists in the People's Republic of China.
      Like atropine and scopolamine, anisodamine is a non-specific cholinergic
      antagonist exhibiting the usual spectrum of pharmacological effects of this drug
      class. It appears to be less potent and less toxic than atropine and displays
      less CNS toxicity than scopolamine. Anisodamine has been shown to interact with
      and disrupt liposome structure which may reflect its effects on cellular
      membranes. Experimental evidence implicates anisodamine as an anti-oxidant that
      may protect against free radical-induced cellular damage. Its cardiovascular
      properties include depression of cardiac conduction and the ability to protect
      against arrhythmia induced by various agents. Anisodamine is a relatively weak
      alpha(1) adrenergic antagonist which may explain its vasodilating activity. Its
      anti-thrombotic activity may be a result of inhibition of thromboxane synthesis.
      The T(1/2) of anisodamine in humans is about 2-3 h. Numerous therapeutic uses of
      anisodamine have been proposed including treatment of septic shock, various
      circulatory disorders, organophosphorus (OP) poisoning, migraine, gastric ulcers,
      gastrointestinal colic, acute glomerular nephritis, eclampsia, respiratory
      diseases, rheumatoid arthritis, obstructive jaundice, opiate addiction, snake
      bite and radiation damage protection. The primary therapeutic use of anisodamine
      has been for the treatment of septic shock. Several mechanisms have been proposed
      to explain its beneficial effect though most mechanisms are based upon the
      assumption that anisodamine ultimately acts by an improvement of blood flow in
      the microcirculation. Preliminary studies suggest another important therapeutic
      use of anisodamine is for the treatment of OP poisoning. Additional research is
      needed to delineate further the clinical usefulness of anisodamine relative to
      other anti-muscarinic drugs such as atropine and scopolamine.

PMID- 17186569
TI  - Lipid peroxidation is enhanced in Yusho victims 35 years after accidental
      poisoning with polychlorinated biphenyls in Nagasaki, Japan.
AB  - Thirty-five years have passed since the accidental poisoning with polychlorinated
      biphenyls (PCB) in Japan and yet high concentrations of PCB are still detected in
      the serum of the victims. PCB produces superoxide and thus victims are considered
      to be in a persistent state of oxidative stress. Urinary concentrations of 8
      isoprostane (8IP) in the victims and age-matched controls were measured to assess
      this hypothesis. The mean urinary concentration of 8IP was significantly higher
      than that in the controls. There was a positive correlation between urinary 8IP
      and serum concentrations of cholinesterase. It was considered that Yusho is an
      oxidative stress and 8IP is a useful tool for checking the oxidative condition in
      Yusho victims.

PMID- 17186570
TI  - The association of alcohol dependency with employment probability: evidence from
      the population survey 'Health 2000 in Finland'.
AB  - In this paper, we investigate to what extent alcohol-dependent individuals fare
      worse in the Finnish labour market, using data from a large Finnish health
      survey. We used the DSM-IV criteria for alcohol dependence assessed by a
      composite international diagnostic interview (CIDI). We find that there are
      substantial disadvantages for alcohol-dependent men and women in the labour
      market, in the sense that they have lower employment probabilities. Treating
      alcohol dependence as an exogenous variable, we find that alcohol dependence is
      associated with decrease in the probability of full-time or part-time work of
      around 14 percentage points for men and 11 percentage points for women. However,
      accounting for endogeneity increases the negative effect to some 50 percentage
      points for men and to some 40 percentage points for women.

PMID- 17186571
TI  - Direct analysis of 15N-label in amino and amide groups of glutamine and
      asparagine.
AB  - A novel method for on-line determination of the amount and position of 15N
      labeling in complex mixtures of amino acids is presented. Underivatized amino
      acids were analyzed by ion-pair chromatography in combination with mass
      spectrometry. This enables the direct determination of the 15N label
      distribution. The fragmentation pathways of the nitrogen moieties of glutamine
      (Gln) and asparagine (Asn) were studied in detail using all mono 15N isotopomers,
      which led to a method for differentiating between 15N-amide and 15N-amino
      labeling. The fragmentation involving the amino and amide groups of Gln led to
      distinct ion structures. The equivalent fragmentation pattern was not observed
      for Asn. Instead, the amide group of Asn was eliminated as HNCO in a secondary
      process. The developed analytical method was evaluated by analysis of a range of
      standard mixtures taking into account different levels of 15N abundance and
      distribution between the amino and amide groups. The detection limit (3 SD) for
      the presence of a 15N label was 0.7 and 1.0% for Gln and Asn, respectively. The
      determination of the positional labeling follows a nonlinear function. A
      representative example at 30% 15N was used as a benchmark resulting in average
      relative standard deviations of 2.7 and 15% for Gln and Asn, respectively. The
      corresponding expectation windows for the positional labeling were found to be 2
      and 12%, respectively.

PMID- 17186572
TI  - Citrinin and endosulfan induced teratogenic effects in Wistar rats.
AB  - Dietary exposures to food pollutants such as mycotoxin(s) or pesticide(s) are
      most significant due to their adverse effects on the production and reproduction
      in animals and the human population. The present investigation was conducted to
      evaluate the teratogenic potential of citrinin (CIT) and endosulfan either alone
      or in combination in pregnant rats during gestational days 6-20. Endosulfan (1 mg
      kg(-1) body weight, by oral intubation) and CIT (10 mg kg(-1) feed, through diet)
      when administered either alone or in combination in pregnant rats caused
      significant teratogenic effects in the developing fetuses. There was no maternal
      mortality, however, reduced maternal weight gain and number of live fetuses and
      increased fetal resorptions were recorded in all the treated groups. The fetal
      body weights and crown to rump lengths were significantly decreased and the per
      cent gross, visceral and skeletal anomalies were significantly increased in the
      fetuses of dams of all the treated groups. The internal hydrocephalus, cerebellar
      hypoplasia, microphthalmia, contracted and notched kidneys, multilobulated liver,
      dilated renal pelvis, incomplete ossification of skull bones, rib anomalies and
      sacral and caudal vertebrae agenesis were the important fetal malformations. The
      occurrence of fetal gross, skeletal and visceral malformations was more severe in
      the combination group, suggesting an additive interaction of CIT and endosulfan
      in inducing developmental toxicity in Wistar rats.

PMID- 17186574
TI  - Methodological aspects on measurement of Clara cell protein in urine as a
      biomarker for airway toxicity, compared with serum levels.
AB  - The Clara cell protein CC16, secreted from Clara cells in the lung, is discussed
      as a potential biomarker for toxic effects on the airways. An increased
      concentration of CC16 in serum may be caused by increased permeability of the
      lungs, caused by high levels of air pollution. Since CC16 is eliminated by renal
      excretion, it may be possible to use urine instead of serum samples. Few studies
      have been conducted on urinary CC16 (U-CC16), however. The aim was to investigate
      the optimal way of sampling and quantifying CC16 in urine samples and compare
      CC16 in human serum and urinary samples. Repeated sampling was performed in two
      groups of healthy subjects. First morning urine, 24 h urine, and matched blood
      and urine samples were collected. The excretion of U-CC16 increased over the day,
      e.g. from 0.08 microg h(-1) in the morning to 0.28 microg h(-1) in daytime and
      0.16 microg h(-1) in the evening (medians in males). Morning samples (microg h(
      1)) from males properly reflected the 24 h excretion (r = 0.91). The best
      correlation with 24 h excretion was obtained with creatinine-corrected first
      morning urine samples (r > 0.9). Generally, females had lower excretion of CC16
      than males (medians 2.5 microg 24 h(-1) in females and 16 microg 24 h(-1) in
      males). There was significant intraindividual variation, but the interindividual
      variation was larger in both groups. There was an association between serum CC16
      (S-CC16) and U-CC16 in morning samples. With optimal methods for sampling U-CC16,
      urine samples may be used in experimental studies of air pollution.

PMID- 17186573
TI  - Human airway surface epithelial regeneration is delayed and abnormal in cystic
      fibrosis.
AB  - Cystic fibrosis (CF) at an advanced stage of the disease is characterized by
      airway epithelial injury and remodelling. Whether CF remodelling is related to
      infection and inflammation or due to an abnormal regenerative process is still
      undecided. We have recently established the expression and secretion profiles of
      interleukin (IL)-8, matrix metalloproteinase (MMP)-7, MMP-9, and tissue inhibitor
      of metalloproteinase (TIMP)-1 during non-CF airway epithelial regeneration in a
      humanized nude mouse xenograft model. To enhance our understanding of CF
      remodelling, we compared the regeneration process of non-infected human CF and
      non-CF nasal epithelia. In both CF and non-CF situations, epithelial regeneration
      was characterized by successive steps of cell adhesion and migration,
      proliferation, pseudostratification, and terminal differentiation. However,
      histological examination of the grafts showed a delay in differentiation of the
      CF airway epithelium. Cell proliferation was higher in the regenerating CF
      epithelium, and the differentiated CF epithelium exhibited a pronounced height
      increase and basal cell hyperplasia in comparison with non-CF epithelium. In
      addition, while the number of goblet cells expressing MUC5AC was similar in CF
      and non-CF regenerated epithelia, the number of MUC5B-immunopositive goblet cells
      was lower in CF grafts. The expression of human IL-8, MMP-7, MMP-9, and TIMP-1
      was enhanced in CF epithelium, especially early in the regenerative process.
      Together, our data strongly suggest that the regeneration of human CF airway
      surface epithelium is characterized by remodelling, delayed differentiation, and
      altered pro-inflammatory and MMP responses.

PMID- 17186575
TI  - Differential responses of biomarkers in tissues of a freshwater mussel, Dreissena
      polymorpha, to the exposure of sediment extracts with different levels of
      contamination.
AB  - In this study, zebra mussels, D. polymorpha, were exposed to extracts of
      sediments obtained from two sites, a contaminated lake (Ketelmeer, Km) and a
      relatively clean lake (Drontenmeer, Dm). The main objective of this work was to
      investigate whether six selected biomarkers could discriminate between the two
      sediments. The selected biomarkers included phase I enzymes such as DT
      diaphorase, NADPH-cytochrome c reductase, NADH-cytochrome c reductase, a phase II
      enzyme (glutathione S-transferase, GST), an antioxidant enzyme, catalase, and the
      total glutathione, reduced (GSH) and oxidized (GSSG). After a short (24 h) and a
      long-term (7 days) exposure, the levels of these biomarkers were measured in
      gills and the rest of soft mussel tissues (soft mussel tissue minus gills) and
      compared with control values. A decrease of GST level by 20% (P = 0.004) and a 4
      fold decrease of total glutathione concentration relative to the control, were
      observed in the gills of mussels exposed to the more contaminated Km extract. No
      significant differences in the GST activities were observed in the gills of
      control and Dm extract-treated mussels (P = 0.23). Although the levels of
      catalase and NADH-cytochrome c reductase were, in the short-term exposure,
      unaffected, both activities were, in the long-term exposure, reduced in the gills
      of the mussels exposed to the contaminated Km extract, compared with control
      values, by 43% and 20%, respectively. The activities of DT-diaphorase and NADPH
      cytochrome c reductase remained unaffected in all exposure conditions. However,
      the level of NADPH-cytochrome c reductase was found higher in gills than in the
      rest of soft mussel tissues. This difference in the ratio of the two reductases
      between the two tissues could account for the observed differential responses of
      the biomarkers.

PMID- 17186577
TI  - A new sleeping pill.

PMID- 17186578
TI  - Report from the XVI International AIDS Conference. "KLEAN" results with
      fosamprenavir/ritonavir.

PMID- 17186576
TI  - Effects of methyl paraben on skin keratinocytes.
AB  - Some ingredients of dermatological formulations result in skin irritation and
      allergy. In particular, preservatives have been reported extensively as a cause
      of allergic contact dermatitis. The study focused on parabens which have been
      used extensively as antimicrobial preservatives in foods, drugs and cosmetics.
      The aim of this study was to clarify the effects of the daily use of methyl
      paraben (MP) on human skin. The concentrations of MP in the stratum corneum (SC)
      of the human forearm were measured using the cup method and GC-MS after daily
      applications of MP containing formulations. The study also investigated the
      effects of long-term exposure to MP on keratinocytes in vitro. Normal human
      keratinocytes and the skin equivalents were cultured in the medium containing MP.
      The following changes were analysed: proliferating ability, apoptotic cells,
      morphological changes, mRNA and protein expressions. After 1 month of daily
      applications of MP containing formulations, MP remained unmetabolized and
      persisted slightly in the SC. MP decreased the proliferating ability of
      keratinocytes and changed the cell morphology. MP also decreased the expressions
      of hyaluronan synthase 1 and 2 mRNAs and type IV collagen. In contrast, it
      increased the expressions of involucrin and HSP27. Furthermore, MP influenced the
      epidermal differentiation of the skin equivalent. These results suggest that MP
      exposure through application of dermatological formulations results in MP
      persistence and accumulation in the SC, and that MP might influence the aging and
      differentiation of keratinocytes.

PMID- 17186579
TI  - Report from the XVI International AIDS Conference. Which antiretroviral regimen
      first? Data from CPCRA.

PMID- 17186580
TI  - Report from the XVI International AIDS Conference. Lopinavir/ritonavir
      monotherapy.

PMID- 17186581
TI  - Report from the XVI International AIDS Conference. CCR5 inhibitors.

PMID- 17186582
TI  - Report from the XVI International AIDS Conference. Preexposure prophylaxis
      studies move forward.

PMID- 17186583
TI  - Viewpoint: Progress and problems for Turkish interventional cardiologists.

PMID- 17186584
TI  - The 2006 Tanner-Vandeput- Boswick Burn Prize awarded.

PMID- 17186585
TI  - Overweight, obesity, and mortality.

PMID- 17186586
TI  - Overweight, obesity, and mortality.

PMID- 17186587
TI  - Cerebral aneurysms.

PMID- 17186588
TI  - Expanding the minority biomedical pipeline: the NIDDK National High School Summer
      Research Program.

PMID- 17186589
TI  - [Skin cancer prevention in the family].

PMID- 17186591
TI  - Medicare critique under fire. AHIP, CMS dispute Commonwealth Fund's findings.

PMID- 17186592
TI  - JCAHO's new data plan, Patient data will be collected to check accuracy.

PMID- 17186593
TI  - Evaluating disease management. DMAA's new guidelines assess healthcare outcomes.

PMID- 17186594
TI  - Animal products and anaesthesia.

PMID- 17186595
TI  - Induced electrical currents in coil systems.

PMID- 17186590
TI  - Vitamin E in renal therapeutic regiments.
AB  - Administration of vitamin E in children with immunoglobulin A (IgA) nephropathy,
      focal segmental glomerulosclerosis (FSGS) and type I diabetes demonstrated
      potential towards ameliorating progression. Oral vitamin E therapy reduced
      endothelial dysfunction, lipid peroxidation and oxidative stress in patients with
      chronic kidney failure (CKF). Moreover, the use of vitamin E-bonded hemodialyzers
      reduced atherosclerotic changes, erythropoietin dosage and muscular cramps in
      patients on hemodialysis (HD). However, several controlled clinical trials failed
      to document beneficial effects on the study subjects' cardiovascular and renal
      outcomes. A recent report of increased all-cause mortality in adult patients
      receiving high dose vitamin E therapy has caused considerable concern and debate.
      These issues regarding the efficacy and safety of vitamin E in renal therapeutic
      regimens will be reviewed in this article.

PMID- 17186596
TI  - Back pain: to cut or not to cut.

PMID- 17186597
TI  - Checkup on Democrats. Industry optimistic healthcare will be a top priority.

PMID- 17186598
TI  - Judge to feds: pick up the pace. Longtime device case called burden on hospitals.

PMID- 17186599
TI  - Rethinking specialty hospitals. Wyo., Texas reports say no permanent harm done.

PMID- 17186600
TI  - Depressed skull fracture.

PMID- 17186601
TI  - Diet DASH-es hypertension.

PMID- 17186602
TI  - Finding peace through hospice care.

PMID- 17186603
TI  - When nature calls too often.

PMID- 17186604
TI  - Depression and diabetes: how big is your team?

PMID- 17186605
TI  - Working out frequent fainting spells.

PMID- 17186606
TI  - Why are placebos important in clinical trials, and why do they sometimes "work"?

PMID- 17186607
TI  - How to read your blood test results. A closer look at these 7 numbers can reveal
      new ways to protect your cardiac health.

PMID- 17186608
TI  - A new caution for patients with drug-coated stents.

PMID- 17186609
TI  - Comfort foods for heart health. 4 ways to improve your diet while preserving the
      best of home cooking.

PMID- 17186610
TI  - New findings on women's hearts. Researchers are learning more about threats
      lurking in small cardiac vessels.

PMID- 17186611
TI  - Going public about malfunctions. New recommendations: makers would tell patients
      about implant problems.

PMID- 17186612
TI  - Ask the doctors. I'm worried that plaque might be jarred loose during my monthly
      heavy massages, especially in the carotid area. Is this possible?

PMID- 17186613
TI  - Accountability.

PMID- 17186615
TI  - Focus on hepatitis. More on the link between HCV, drugs, unprotected sex.

PMID- 17186614
TI  - HIV, HBV, and HCV in Europe: border crossings and buried tombs. IAPAC European
      sessions 2005. October 6-7, 2005. Amsterdam, The Netherlands.

PMID- 17186616
TI  - Sequence homology to the Drosophila per locus in higher plant nuclear DNA and in
      Acetabularia chloroplast DNA.
AB  - In plant cells a DNA sequence was found which is homologous to the Drosophila per
      locus. In rape and spinach the homologous sequence occurs in the nuclear but not
      in the chloroplast genome while in Acetabularia it is found in the chloroplast
      but not in the nuclear genome. A 1.175 kb EcoRi-SalI fragment of the chloroplast
      genome of Acetabularia containing the homologous sequence was subcloned into
      pUC12 and sequenced. The core of the 1.175 kb fragment is a repetitive tandemly
      arranged sequence of 43 units of the hexamer GGA ACT coding for glycine and
      threonine.

PMID- 17186617
TI  - Different transcript  abundance of two divergent ATP synthase subunit 9 genes in
      the mitochondrial genome of Petunia hybrida.
AB  - The mitochondrial genome of Petunia hybrida line 3704 has been found to contain
      two transcribed genes for the proteolipid subunit of the ATP synthase complex
      (atp 9). The 5' and 3' flanking sequences of the second atp 9 gene differ from
      those of another atp 9 gene previously sequenced by Young et al. (1986), while
      the coding region exhibits only one silent base change. The transcript termini of
      the two divergent atp 9 genes map to different locations, most of which are
      surrounded by sequences homologous to putative mitochondrial transcription
      signals (Hiesel and Brennicke 1985; Schuster et al. 1986; Young et al. (1986).
      Because transcripts from the atp 9 genes differ in abundance, divergence in the
      flanking regions of these two genes must affect regulatory elements which control
      either transcription rate or transcript stability.

PMID- 17186618
TI  - A novel wheat alpha-amylase gene (alpha-Amy3).
AB  - A genomic clone of a wheat alpha-amylase gene (lambdaAmy3/33) was identified, on
      the basis of hybridisation properties, as different from alpha-Amy1 and alpha
      Amy2 genes which had been characterised previously. The nucleotide sequence
      revealed that this gene has the normal sequence motifs of an active gene and an
      open reading frame interrupted by two introns. The protein sequence encoded by
      this open reading frame is recognisably similar to that of alpha-amylase from the
      alpha-Amy1 and alpha-Amy2 genes and there is high sequence homology in all three
      proteins at the putative active sites and Ca++ binding region. In addition, the
      introns are at positions equivalent to the position of introns in the alpha-Amy1
      and alpha-Amy2 genes. However, the sequence was less similar to alpha-Amy1 and
      alpha-Amy2 than these are to each other. Southern blot analysis showed that the
      lambdaAmy3/33 DNA is one of a small multigene family carried on a different
      chromosome (group 5) from either the alpha-Amy1 or alpha-Amy2 genes. A further
      difference from the alpha-Amy1 and alpha-Amy2 genese was the pattern of
      expression. lambdaAmy3/33 was expreseed only in immature grains and, unlike the
      alpha-Amy1 and alpha-Amy2 genes, not at all in germinating aleurones. These data
      suggested therefore that this gene represents a third type of alpha-amylase gene,
      not described before, which shares a common evolutionary ancestor with the alpha
      Amy1 and alpha-Amy2 genes.

PMID- 17186619
TI  - Insertional DNA and spontaneous mutation at the white locus in Drosophila
      simulans.
AB  - A large body of data on molecular analyses of several multiallelic loci in
      Drosophila melanogaster has demonstrated a high incidence of mobile DNA element
      insertions among spontaneous mutations. In the sibling species D. simulans, the
      dispersed, middle repetitive, nomadic sequences are reduced to about one-seventh
      that of its sibling species (Dowsett and Young 1982). Does this reduced amount of
      middle repetitive DNA (or mobile DNA sequences) mean that in D. simulans the
      occurrence of insertion mutants will be rare compared with that of D.
      melanogaster? To test this possibility, we collected seven different spontaneous
      white mutants of D. simulans and studied their molecular gene structures. Five
      out of seven mutants had insertion sequences which varied in length from 0.4 kb
      to 16 kb. One bore a deletion spanning the w region and another showed no gross
      structural alteration. Thus the proportion of insertional mutations at the white
      locus in D. simulans is equivalent to that observed in D. melanogaster. Among the
      five insertional mutants, one, wmky, showed genetic instability; the other four
      were stable. wmky was found to mutate at a frequency of 2.1 x 10(-5) in meiotic
      cells and may also be unstable in somatic cells.

PMID- 17186620
TI  - Regions in the transit peptide of SSU essential for transport into chloroplasts.
AB  - Deletion mutations, 3-19 amino acids in size, were introduced into the transit
      peptide (57 amino acids) of a small subunit (SSU) of ribulose-1,5-bisphosphate
      carboxylase/oxygenase from pea. Transport of the authentic small subunit
      precursor (pSSU) and of the mutant pSSUs by isolated chloroplasts of pea was
      examined. We show that the transit peptide contains two different, separated
      functional regions. A deletion mutation in the central region of the transit
      peptide, a region purported to be important for function, barely affected
      transport. Changes in the amino-terminal region of the transit peptide appeared
      normal. A deletion mutation at the carboxy-terminus of the transit peptide
      interfered with both transport and processing. From the aberrant processing we
      suggest that pSSU is matured in more than one step, and that the maturation
      signal is located within the carboxy-terminal 16 amino acids. The methionine
      residue at the evolutionarily conserved cleavage site (cysteine-methionine)
      between the transit peptide and the mature protein is not essential processing.

PMID- 17186621
TI  - Spore activation by acetate, propionate and heat in Phycomyces mutants.
AB  - Exposure to heat, acetate, or propionate activates the spores of the fungus
      Phycomyces blakesleeanus and allows them to germinate. Using counterselection
      with the antibiotic N-glycosyl-polyfungin, seven mutants were isolated on the
      basis of decreased spore activation by propionate. The nine mutants showed
      decreased activation by both chemicals and by heat, increased heat lethality, and
      altered patterns of trehalase activation. These and other observations indicate
      that spore activation by the three agents and spore death by heat are mediated by
      the same cellular component(s), which is probably involved in the regulation of
      cyclic AMP concentration.

PMID- 17186622
TI  - Functional cybrid plants possessing a Nicotiana genome and an Atropa plastome.
AB  - Mesophyll protoplasts of plastome chlorophyll-deficient, streptomycin-resistant
      Nicotiana tabacum were fused with those of wild type Atropa belladonna using the
      polyethylene-glycol/high Ca++/dimethylsulfoxide method. Protoplasts were cultured
      in nutrient media suitable for regeneration of tobacco but not Atropa cells. In
      two experiments, a total of 41 cell lines have been selected as green colonies.
      Cytogenetic (chromosomal number and morphology) and biochemical (isozyme analyses
      of esterase, amylase and peroxidase) studies were used to evaluate the nuclear
      genetic constitution of regenerated plants. To study plastid genetic
      constitution, restriction endonuclease analysis of chloroplast DNA was performed.
      Three groups of regenerants have been identified: (a) nuclear hybrids (4 cell
      lines); (b) Atropa plants, most probably arising from rare surviving parental
      protoplasts (4 lines) and (c) Nicotiana/Atropa cybrids possessing a tobacco
      genome and an Atropa plastome (33 lines). Most of cybrids obtained were diploid,
      morphogenetically normal plants phenotypically similar to tobacco. Some plants
      flowered and yielded viable seeds. Part of cybrid regenerants were variegated,
      variegation being transmitted to sexual progeny. Electron microscopic analysis of
      the mesophyll cells of variegated leaves revealed the presence of heteroplastidic
      cells. Analysis of thylakoid membrane polypeptides shows that in the cybrids the
      content of at least one of the major polypeptides, presumably a chlorophyll a/b
      binding protein is drastically reduced.

PMID- 17186623
TI  - Cloning of the Bz2 locus of Zea mays using the transposable element Ds as a gene
      tag.
AB  - The Bz2 locus of Zea mays has been cloned, utilizing the presence of the
      transposable element Dissociation (Ds) at the locus as a gene flag. The Ds
      element inserted in the bz2-m allele was identified among many members of the
      Ac/Ds family in a Southern blot analysis of a population segregating for bz2-m
      and Bz2. After cloning a DNA fragment from the bz2-m allele, sequences flanking
      the Ds insertion were shown to be Bz2-specific and were used to isolate a
      homologous fragment from a wild-type Bz2 line. The Ds insertion in the bz2-m
      allele was found to be a Ds2 element identical to the Ds insertion in adh1-2F11.

PMID- 17186624
TI  - Transposable element Ds2 of Zea mays influences polyadenylation and splice site
      selection.
AB  - In the allele adh1-2F11 of Zea mays the 1.3 kb transposable element Ds2 is
      inserted in the fourth exon of Adh1. Two major RNAs of 3.0 and 1.6 kb are
      transcribed from this allele. While the 3.0 kb transcript also contains the Ds2
      sequences, the 1.6 kb transcript has lost the Ds2 sequences by an alternative
      splicing process. In this process, a normal 5' splice site is joined to a cryptic
      3' splice site located within exon 4. This cryptic 3' splice site is not used in
      a wild-type Adh1F allele. Other minor transcripts of adh1-2F11 are prematurely
      terminated and polyadenylated.

PMID- 17186626
TI  - Diet and time of day strongly influence metabolomic studies.

PMID- 17186625
TI  - A new unified framework for making and implementing decisions.

PMID- 17186627
TI  - Biosensor to help Crohn's disease patients.

PMID- 17186628
TI  - Controlling ion-channel desensitization.

PMID- 17186629
TI  - New mitochondrial DNA profiling technique for forensics.

PMID- 17186630
TI  - Chilean fertilizer leaves perchlorate legacy.

PMID- 17186631
TI  - Closing the gap in membrane imaging.

PMID- 17186632
TI  - Microfluidic field-effect device for heparin.

PMID- 17186633
TI  - Dynamic single-cell analysis for quantitative biology.

PMID- 17186634
TI  - Weighing ribosomes with MS.

PMID- 17186635
TI  - Atomic force and optical microscopy align themselves.

PMID- 17186636
TI  - Confocal microscopy: not just for pretty pictures.

PMID- 17186637
TI  - Position of the American Dietetic Association: Nutrition intervention in the
      treatment of anorexia nervosa, bulimia nervosa, and other eating disorders.
AB  - It is the position of the American Dietetic Association that nutrition
      intervention, including nutritional counseling, by a registered dietitian (RD) is
      an essential component of the team treatment of patients with anorexia nervosa,
      bulimia nervosa, and other eating disorders during assessment and treatment
      across the continuum of care. Diagnostic criteria for eating disorders provide
      important guidelines for identification and treatment. However, it is thought
      that a continuum of disordered eating may exist that ranges from persistent
      dieting to subthreshold conditions and then to defined eating disorders, which
      include anorexia nervosa, bulimia nervosa, and binge eating disorder.
      Understanding the complexities of eating disorders, such as influencing factors,
      comorbid illness, medical and psychological complications, and boundary issues,
      is critical in the effective treatment of eating disorders. The nature of eating
      disorders requires a collaborative approach by an interdisciplinary team of
      psychological, nutritional, and medical specialists. The RD is an integral member
      of the treatment team and is uniquely qualified to provide medical nutrition
      therapy for the normalization of eating patterns and nutritional status. RDs
      provide nutritional counseling, recognize clinical signs related to eating
      disorders, and assist with medical monitoring while cognizant of psychotherapy
      and pharmacotherapy that are cornerstones of eating disorder treatment.
      Specialized resources are available for RDs to advance their level of expertise
      in the field of eating disorders. Further efforts with evidenced-based research
      must continue for improved treatment outcomes related to eating disorders along
      with identification of effective primary and secondary interventions.

PMID- 17186639
TI  - [Proceedings of the VIII Congress of the International Association of
      Morphologists. Abstracts. September 15, 2006, Orel, Russia].

PMID- 17186638
TI  - Sinonasal carcinoma masquerading as fungal sinusitis.
AB  - A 26-year-old man presented with swelling of his face and nose of three months
      duration. He had multiple hyperpigmented, hyperkeratotic plaques over the
      swelling, of one-month duration and an erythematous indurated plaque below the
      left nostril for two weeks. Based on a biopsy taken from the antral mass with
      special stain for fungus, he was treated as fungal sinusitis with intravenous
      amphotericin-B, but the lesion did not regress. Later a skin biopsy from the
      indurated lesion showed moderately differentiated squamous cell carcinoma. A
      diagnosis of sinonasal carcinoma was made and chemotherapy was started.

PMID- 17186640
TI  - Associations of physical activity and body mass index with activities of daily
      living in older adults.
AB  - Research reports about the associations of leisure-time physical activity (LPA)
      and Body Mass Index (BMI) with activities of daily living (ADL)- or instrumental
      activities of daily living (IADL)-dependent disability in older adults are
      inconclusive. Data were obtained from the 2000 Missouri Older Adult Needs
      Assessment Survey. Logistic regression was used to examine the associations of
      LPA and BMI with ADL- or IADL-dependent disability, while controlling for factors
      known to be associated with LPA, BMI, ADL and IADL. ADL- or IADL-dependency
      decreased with LPA and increased with BMI regardless of each other's level,
      presence of functional limitation, education, gender, race-ethnicity, and health
      care coverage. Physically active individuals were less likely than inactive ones
      to be ADL- or IADL-dependent. BMI was modestly associated with ADL- or IADL
      dependency and this relationship was confounded by LPA. If confirmed by well
      designed longitudinal studies, LPA and BMI independent associations with ADL- or
      IADL-dependent disability lends supports to a strategy for improving older adult
      quality of life through improved physical activity. Etiological studies on the
      associations between risk factors and quality of life outcomes in older adults
      should consider the joint confounding effect of LPA and BMI.

PMID- 17186641
TI  - Relationship between asthma, overweight, and physical activity among U.S. high
      school students.
AB  - Asthma is a leading chronic illness among children and adolescents in the United
      States. This study examined the relationship between asthma and both overweight
      and physical activity levels. Results are based on data from the Centers for
      Disease Control and Prevention's 2003 national Youth Risk Behavior Survey, a
      cross-sectional survey of health risk behaviors among a representative sample of
      high school students in the United States. The overall survey response rate was
      67% and the results are based on weighted data. SUDAAN was used for all data
      analysis (prevalence estimates and logistic regression) because it accounts for
      the complex sampling design of the survey. Significantly more students with
      current asthma than without were overweight (odds ratio [OR] = 1.4; 95%
      confidence interval [CI] = 1.1, 1.6) and described themselves as overweight (OR =
      1.2; 95% CI = 1.0, 1.4). Significantly more students with current asthma than
      without used a computer for non-schoolwork 3 or more hours/day (OR = 1.3; 95% CI
      = 1.1, 1.5). No significant differences were found for participation in
      sufficient vigorous or moderate physical activity or strengthening exercises
      among students with and without current asthma. Unlike some other risk factors
      for developing or exacerbating asthma, overweight and physical activity are
      generally modifiable. School and community policies and programs can play an
      important role in asthma management, including promoting the maintenance of an
      appropriate weight and encouraging continued physical activity.

PMID- 17186642
TI  - A local community health survey: findings from a population-based survey of the
      largest Jewish community in Chicago.
AB  - Accurate estimates of health risk factors and outcomes are difficult to obtain
      for certain ethnic populations. The health of Jewish individuals is particularly
      hard to determine because of the small group size and because health data rarely
      include information on religious affiliation. Furthermore, local level health
      information (for any population subgroup) is limited. To assess health risk
      factors and outcomes, as well as issues related to access to care, within a
      Jewish community in Chicago, a group of community agencies and researchers
      initiated a unique, population-based health survey. Specifically, a three-stage
      sampling design was used to select a representative sample of 201 adults and 58
      children in the most concentrated Jewish neighborhood in the city. Nearly 500
      questions were asked, covering a wide variety of demographic, socioeconomic, and
      health-related topics. The findings revealed that these Jewish individuals were
      generally as healthy (or healthier) than the average residents of Chicago and the
      U.S.; however, many serious health concerns still existed. In particular, health
      problems such as obesity, depression, disability, and domestic violence were
      common and, in some cases, more prevalent than in the general population. This
      local level information provides the first accurate estimates of key health
      variables for the estimated 23,000 Jewish individuals living in this community.
      This type of data is essential because it enables the efforts and priorities of
      health and social service providers to be focused on the most pressing health
      problems. Moreover, this project provides an example for other population
      subgroups (based on residence, ethnicity, religious affiliation, country of
      origin, or other characteristics) who would benefit from local level health
      information.

PMID- 17186643
TI  - Improving rescreening in community clinics: does a system approach work?
AB  - Community clinics provide inadequate breast cancer screening services to low
      income, racially- and ethnically-diverse communities. This study develops and
      evaluates the effectiveness of multifaceted organizational system interventions-
      operational assessments, tracking systems, reminder calls, tailored education,
      physician prompts and a tailored counseling call--on mammography rescreening
      rates within three community clinics. We used the Chronic Care Model and Put
      Prevention Into Practice framework to redesign breast screening delivery services
      within the California Cancer Detection Programs: Every Woman Counts (CDP:EWC),
      community clinic settings. We used a quasi-experimental design with a random
      selection of 400 patients at pre-intervention. To establish a post-intervention
      clinic's rescreening rate a new comparable cross-sectional random sample of 347
      women was drawn. Measures A chart abstraction instrument was used to establish
      clinics' rescreening rates. Subjects participants at pre and post-intervention
      were low-income women 50 years of age and older who had received normal
      mammography results and had not been diagnosed with breast cancer in the last
      five years. General linear mixed model analysis revealed significant improvements
      for the organizational system redesign condition [pre-intervention rescreening
      rate: 32.1 percent v. post-intervention rescreening rate 50.2 percent, (p <
      .001)]. For the organizational system redesign plus tailored counseling call
      condition, there was maintenance in the rescreening rate following the
      intervention [pre-intervention: 44.4 percent v. post-intervention: 45.1 percent,
      (p > 0.05)]. Multilevel interventions directed at redesigning community clinics
      primary care breast cancer screening services, can improve mammography
      rescreening rates.

PMID- 17186644
TI  - Disproportionate impact of diabetes in a Puerto Rican community of Chicago.
AB  - We assessed the impact of diabetes in a large Puerto Rican community of Chicago
      by measuring the prevalence of diagnosed diabetes and calculating the diabetes
      mortality rate. Data were analyzed from a comprehensive health survey conducted
      in randomly selected households in community areas. Questions on diagnosed
      diabetes and selected risk factors were asked. In addition, vital records data
      were analyzed in order to calculate the age-adjusted diabetes mortality rate.
      When possible, rates were compared to those found in other studies. The diabetes
      prevalence located in this community (20.8%: 95% CI = 10.1%-38.0%) is the highest
      ever reported for Puerto Ricans and one of the highest ever reported in the
      United States for a non-Native American population. For instance, it is twice the
      prevalence for Puerto Ricans in New York (11.3%) and Puerto Rico (9.3%-9.6%).
      Diagnosed diabetes was found to be significantly associated with obesity (p =
      0.023). The prevalence was particularly high among older people, females, those
      born in the US, and those with a family history of diabetes. Notably, the
      diabetes mortality rate (67.6 per 100,000 population) was more than twice the
      rate for all of Chicago (31.2) and the US (25.4). Understanding why the diabetes
      prevalence and mortality rates for Puerto Ricans in this community are so much
      higher than those of other communities is imperative for primary and secondary
      prevention. Collaboration between researchers, service providers and community
      members can help address the issues of diabetes education, early screening and
      diagnosis, and effective treatment needed in this community.

PMID- 17186645
TI  - Determining the prevalence of Escherichia coli O157 in cattle and beef from the
      feedlot to the cooler.
AB  - Prevalence of Escherichia coli O157 on cattle entering the slaughter floor may
      range from 10 to > 70%. This study was conducted to determine the effect of E.
      coli O157 prevalence in fecal pats collected from feedlot pen floors on
      subsequent E. coli O157 prevalence on carcasses at various points in the
      slaughter process. Fecal pats from the feedlot pen floor were collected within 3
      days before slaughter. During cattle processing at the slaughter facility,
      additional samples were collected from the hide, from the colon, and from the
      carcasses before and after evisceration and after final decontamination. Of 15
      lots (a group of cattle from the same pen from a feedlot) sampled, 87% had at
      least one positive fecal pat from the feedlot floor, 47% had a positive hide
      sample, 73% had a positive colon/fecal sample, and 47% had a positive carcass
      sample preevisceration; however, only 8% of lots had a positive carcass sample
      postevisceration or after final intervention. Of the total samples tested (n =
      1,328), 24.7, 14.7, 27.6, 10.1, 1.4, and 0.3% of fecal pats from the feedlot
      floor, hide, colon, preevisceration, postevisceration, and final intervention
      samples, respectively, were positive for E. coli O157. Pens with greater than 20%
      positive fecal pats from the feedlot floor had 25.5% hide, 51.4% colon, and 14.3,
      2.9, and 0.7% carcass samples positive at preevisceration, at postevisceration,
      and after final intervention, respectively. However, fecal pats from feedlot
      floor samples that contained less than 20% positive fecal samples showed lower
      pathogen prevalence, with 5.0% hide, 7.5% colon, and 6.3, 0, and 0% carcass
      positive samples at preevisceration, postevisceration, and post-final
      intervention, respectively. Data from this study can be used as part of risk
      assessment processes in order to identify mitigation strategies to minimize
      prevalence of E. coli O157 on fresh beef carcasses.

PMID- 17186646
TI  - Importance of airborne contamination during dressing of beef and lamb carcasses.
AB  - Carcasses along slaughter lines were exposed to normal slaughterhouse air or
      ultraclean air provided from a unit fitted with a HEPA filter. In cattle
      slaughterhouses, aerobic viable counts were measured by sponging the brisket at
      the end of the line to determine whether the slaughterhouse air had led to
      contamination of the carcasses. Furthermore, a replica cattle carcass with settle
      plates attached was exposed to similar conditions. The greatest contamination of
      the plates occurred at the hide puller (P < 0.01). The use of ultraclean air
      reduced the deposition of organisms onto settle plates (P < 0.01). The airborne
      route contributed to contamination in cattle slaughterhouses, but other vectors
      were more important. Further study of contamination of the brisket, at the time
      that it was first exposed, showed that knives transfer contamination from the
      hide. The use of ultraclean air at this position showed that the airborne route
      was a contributor to contamination (P < 0.1), but it was not the greatest vector.
      In lamb slaughterhouses, the highest counts on settle plates were found at the
      fleece puller (P < 0.05). The highest counts on the lamb carcasses were found on
      the brisket exposed from the start of the line to just after the fleece puller (P
      < 0.05). There was no clear relationship between the measured counts and the
      concentration of organisms in the air, indicating that the airborne route in lamb
      slaughterhouses contributes less to carcass contamination than do the surface
      contacts.

PMID- 17186647
TI  - Setting control limits for Escherichia coli counts in samples collected routinely
      from pig or beef carcasses.
AB  - Records of Escherichia coli counts in samples routinely collected from carcasses
      were obtained from one pork and three beef packing plants. The data obtained from
      each plant were divided into sets from consecutive 6-month periods. For each set
      of counts, log total counts were calculated for subsets of various sizes. For
      each set of log total counts, the mean (x), the standard deviation (SD), and an
      action limit of x + 3 SD were calculated, and the set was tested for a normal
      distribution. With the data from samples collected at the pork packing plant
      during 6 years, the proportion of samples with counts of zero in the 12 sets
      ranged from 15 to 45%. For that plant, appropriate action limits could be derived
      from log total counts for subsets of nine unit values. With the data from samples
      collected during 8 years at one beef packing plant, the proportion of samples
      with counts of zero in the 16 sets ranged from 88 to 99%. For that plant,
      appropriate action limits could be derived from log total counts for subsets of
      15 unit values. With the data from samples collected during 2 or 2.5 years at
      each of the other beef packing plants, the proportion of samples with counts of
      zero in all sets was > 99%. For those data, action limits could not be derived
      from values for subsets of log total counts.

PMID- 17186648
TI  - Screening of bacteria from the cattle gastrointestinal tract for inhibitory
      activity against enterohemorrhagic Escherichia coli O157:H7, O111:H-, and
      O26:H11.
AB  - A quick and reproducible microgel plate assay was adapted to screen bacteria from
      cattle gastrointestinal tracts for production of compounds inhibitory to the
      growth of three enterohemorrhagic Escherichia coli (EHEC) serotypes: O157:H7,
      O111:H-, and O26:H11. The inhibitory activity of 309 bacteria, isolated on
      several agar media, was assessed by a microgel assay performed in 96-well
      microtiter plates. Fifty-three isolates secreted inhibitory compounds with a
      molecular weight of less than 1,000. In 12 isolates, the inhibitory activity was
      attributable to compounds other than lactic or acetic acid. These compounds were
      highly heat tolerant, with varying sensitivity to digestion by proteolytic
      enzymes. The inhibitory isolates were identified as lactic acid-producing
      bacteria on the basis of a combination of analyses, including 16S-rDNA
      restriction fragment length polymorphisms, 16S-rDNA gene sequences, and
      fermentation end products. The lactic acid bacteria of ruminants may contain
      antibacterial compounds not yet described. Naturally occurring populations of
      lactic acid bacteria may have potential as probiotics, to reduce the carriage of
      EHEC in the gastrointestinal tract of ruminants.

PMID- 17186649
TI  - Survival of Escherichia coli O157:H7 in bovine feces over time under various
      temperature conditions.
AB  - Although Escherichia coli O157:H7 prevalence estimates in cattle have increased
      over time due to improvements in detection methods, fecal sample transport
      conditions from farm to microbiological laboratories for further analysis may be
      a factor for prevalence underestimation. The objective of this study was to
      compare and determine the survival characteristics of E. coli O157:H7 in bovine
      feces under various storage conditions that could be encountered during
      transport. Fecal pats were inoculated with a four-strain cocktail of antibiotic
      resistant E. coli O157:H7 to contain approximately 1 x 10(5) CFU/g. Inoculated
      and control samples were taken after 0, 24, 48, 120, and 168 h at each storage
      temperature and examined for presence and numbers of E. coli O157:H7. Each sample
      was subdivided and placed at each of the four following temperatures: 37, 23, 4.4
      degrees C, and in a plastic cooler with refrigerant packs (0, 4, 4, 21, and 23
      degrees C at five sampling times, respectively) to simulate transportation
      conditions. A statistically significant decrease in the population of the
      pathogen was observed after 48 h in samples held at 37 degrees C (P < 0.01) and
      after 168 h at 4.4 degrees C (P = 0.02). At 37 degrees C, E. coli O157:H7 was not
      detected after 48 h, either by direct plating (P < 0.01) or by immunomagnetic
      separation. Overall, the results of this study showed that E. coli O157:H7
      survived without significant detriment in bovine fecal material inside the cooler
      for up to 168 h. These results indicate that shipment and storage under these
      conditions before microbiological analysis would be acceptable and should not
      affect pathogen detection.

PMID- 17186650
TI  - Fate of Escherichia coli strains inoculated in model cheese elaborated with or
      without starter and treated by high hydrostatic pressure.
AB  - The aim of this research was to study high hydrostatic pressure inactivation of
      two strains of Escherichia coli (E. coli O59:H21 [CECT 405] and E. coli O157:H7
      [CECT 5947]) inoculated in washed-curd model cheese elaborated with and without
      starter and the ability of these strains for survival, recovery, and growth.
      Samples were treated at 300, 400, and 500 MPa for 10 min at 20 degrees C and
      analyzed after the treatment and after 1, 7, and 15 days of storage at 8 degrees
      C to study the behavior of Escherichia populations. Cheeses elaborated with
      starter showed the maximum lethality at 400 and 500 MPa, and no significant
      differences in the baroresistant behavior of either strains were detected, except
      for E. coli O157:H7 at 400 MPa in cell counts obtained with thin agar layer
      method medium, where the decrease value was significantly lower. In cheese
      elaborated without starter, the highest decrease value was observed at 500 MPa,
      except for E. coli O59:H21 in cell counts obtained with selective culture medium,
      where the highest decrease value was also found at 400 MPa. The ability to repair
      and grow was not observed in model cheese elaborated with starter, as cell counts
      of treated samples decreased after 15 days of storage at 8 degrees C. By
      contrast, in cheese elaborated without starter, all pressurized samples showed
      the trend to repair and grow during the storage period in both strains. These
      results suggest that the presence of starter and low pH values are the main
      factors that control the ability of Escherichia strains inoculated in this type
      of cheese and treated by high hydrostatic pressure to recover and grow.

PMID- 17186651
TI  - Evaluation of immunomagnetic separation and PCR for the detection of Escherichia
      coli O157 in animal feces and meats.
AB  - Series of animal feces and meat samples artificially contaminated with strains of
      Escherichia coli O157 isolated from different sources were tested by both an
      immunomagnetic separation (IMS)-based method and a PCR method using primers
      specific for a portion of the rfbE gene of E. coli O157. IMS is laborious and
      time consuming but ends up with the isolation of the pathogen. PCR is fast and
      less laborious, but it can only be used for screening purposes, so a further
      culture step is required to isolate the organism. For both fecal and meat
      samples, the IMS method was found to be more sensitive than the PCR. Furthermore,
      the detection efficiency of the PCR was influenced by the origin of the fecal
      sample and the type of meat. For sheep feces, the efficiency of the PCR appeared
      to be systematically lower than for cattle feces. And the efficiency of the PCR
      in detecting E. coli O157 in spiked samples of raw minced beef and dry-fermented
      sausages was systematically lower than in samples of filet americain. Based on
      this study, it can be concluded that both for animal feces and meat, IMS can be
      used more successfully to detect E. coli O157 than PCR, because IMS showed to be
      more sensitive and the outcome was not influenced by the type of animal feces or
      meat.

PMID- 17186652
TI  - Improvement of immunomagnetic separation for Escherichia coli O157:H7 detection
      by the PickPen magnetic particle separation device.
AB  - Conventional immunomagnetic separation (IMS) procedures, which use an external
      magnetic source to capture magnetic particles against the side of a test tube,
      are labor-intensive and can have poor sensitivity for the target organism because
      of high background microflora that is not effectively washed away during the IMS
      process. This report compares the conventional IMS procedure to a new IMS
      procedure with an intrasolution magnetic particle transfer device, the PickPen.
      The IMS target for the majority of these studies is Escherichia coli O157:H7 in
      various types of samples, including cattle feces, hides, carcasses, and ground
      beef. Comparison of the two IMS methods showed a significant difference (P <
      0.05) in the efficiency of detecting E. coli O157:H7 from cattle carcass surface,
      cattle hide, and cattle fecal samples. No significant improvement (P > 0.05) in
      E. coli O157:H7 detection was observed when the PickPen IMS procedure was used to
      isolate this pathogen from ground beef samples. Use of the PickPen IMS greatly
      increases the throughput of the IMS procedure and may be more compatible with
      various emerging technologies for pathogen detection. In addition, the efficacy
      of sequential IMS for multiple pathogens is reported herein.

PMID- 17186653
TI  - Microbiological baseline study of broiler chickens at Swedish slaughterhouses.
AB  - This 1-year study was conducted to estimate the prevalence and concentrations of
      pathogenic and indicator bacteria on Swedish broiler chickens. A total of 636
      chilled carcasses were collected from 10 slaughterhouses and sent to the National
      Food Administration for analyses of carcass rinses. No carcasses were positive
      for Salmonella. Campylobacter, predominantly Campylobacter jejuni, were detected
      on 15% (by enrichment) or 14% (by direct plating) of the carcasses. With one
      exception, all samples from late December through April were Campylobacter
      negative. The 10th and 90th percentiles of Campylobacter numbers per carcasses
      were 3.0 and 5.0 log CFU, respectively, and the maximum was 7.1 log CFU.
      Coagulase-positive staphylococci were detected on 68% of the carcasses, with a
      maximum of 3.5 log CFU/cm2. The 10th and 90th percentiles were 3.4 and 4.4 log
      CFU/cm2 for total aerobic microorganisms, 1.8 and 3.3 log CFU/cm2 for
      Enterobacteriaceae, and 2.0 and 3.6 log CFU/cm2 for Escherichia coli. No
      correlation was found between numbers of any indicator bacteria and numbers of
      pathogenic bacteria. Subsets of the samples were analyzed for Listeria
      monocytogenes, Clostridium perfringens, pathogenic Yersinia enterocolitica, and
      Enterococcus, resulting in prevalence estimates of 29, 18, 9 (as determined by a
      PCR assay), and 97%, respectively. L. monocytogenes was most common at
      slaughterhouses with a low prevalence of coagulase-positive staphylococci, and
      vice versa. These results will improve the ability of researchers to assess the
      importance of chicken as a source of foodborne pathogens and can serve as a basis
      for risk management actions.

PMID- 17186654
TI  - Effects of different molting procedures on incidence of Salmonella infection in
      flocks of naturally contaminated laying hens in a commercial egg-producing farm
      by detection of yolk antibodies to Salmonella in eggs.
AB  - Indirect enzyme-linked immunosorbent assays (ELISAs) have been applied to detect
      immunoglobulin Y antibodies to different serotypes of Salmonella in the yolks of
      chicken eggs with heat-extracted antigens of Salmonella enterica serotypes Agona
      (SA), Cerro (SC), Enteritidis (SE), Montevideo (SM), and Putten (SP). The egg
      yolk samples examined were classified as positive if their ELISA absorbance
      values exceeded the value for eggs from specific-pathogen-free flocks by more
      than two standard deviations. Of 30 egg yolk samples from three flocks vaccinated
      with a killed SE vaccine, 29 were antibody positive by the ELISA assay for the SE
      antigen. Four to 29 of the 29 yolk samples showed positive results for the other
      serovars, although the absorbance values for SE were higher than those obtained
      for the other serotypes in each of the yolk samples. All 30 yolks from three
      flocks that were not administered any SE vaccines were found to be antibody
      negative for SE, and two samples were determined to be positive for SC. Thirty
      nine or 40 eggs were obtained from each of four layer flocks in a commercial egg
      production farm where the laying houses were naturally contaminated with SA, SC,
      SM, SP, Salmonella serovar Infantis (SI), and untypeable strains. The ELISA
      absorbance values for SM in the egg yolks obtained from the two flocks molted
      through feed withdrawal when the birds restarted laying were significantly (P <
      0.05) higher than those observed in the yolks obtained before the molt. In egg
      yolks from the two other flocks that were molted through a wheat bran diet, there
      was no significant difference between the absorbance values before and after the
      molt. The observations in the present study provide further evidence to suggest
      that a molt initiated through the administration of a wheat bran diet can reduce
      the risk for Salmonella problems in a commercial egg-producing setting.

PMID- 17186655
TI  - Influence of commercial sanitizers on lipopolysaccharide production by Salmonella
      Enteritidis ATCC 13076.
AB  - The effect of typical sanitizers on the composition and toxicity of
      lipopolysaccharides (LPSs) produced by Salmonella Enteritidis ATCC 13076 was
      analyzed. Salmonella Enteritidis was propagated up to the late exponential phase
      in the presence of commercial sanitizing solutions. LPS was extracted and
      derivatized with trifluoroacetylation, and gas chromatography-mass spectrometry
      analysis and the chromogenic Limulus amoebocyte lysate assay were used to assess
      the ultrastructure and toxicity of the LPS. The viability and debris formation
      during growth were evaluated to verify the bactericidal and bacteriostatic
      effects of the sanitizers and to assess sanitizer effects on LPS formation. The
      LPSs produced were quantified at 1.7 x 10(4), 1.2 x 10(4), 3.6 x 10(3), and 9.6 x
      10(4) [KDO] x OD(620nm)(-1) for the controls and the organisms grown in the
      presence of a chlorinated sanitizer, a heavy-duty alkaline cleaner, and a
      phenolic hand wash solution, respectively. In response to these treatments, the
      short-chain polysaccharide fractions of the LPSs in the Salmonella Enteritidis
      cells increased. This finding suggests that this organism increases the low
      molecular-weight fraction of the LPS in relation to the high-molecular-weight
      fraction to survive these unfavorable conditions. The cumulative change in the
      LPS in response to the sanitizers influenced the toxicity of the LPS; however,
      this change could not be related to an individual compound within any of the
      assessed fractions.

PMID- 17186656
TI  - Evaluation of an immunomagnetic separation-real-time PCR assay for the rapid
      detection of Salmonella in meat.
AB  - The aim of this study was the comparison of an immunomagnetic separation (IMS)
      real-time PCR assay for the detection of Salmonella with the cultural reference
      method according to and 35 of the German Law on Food and Commodities (LMBG, L
      00.00.20:1998). The IMS-real-time PCR assay includes a nonselective preenrichment
      step, an IMS, DNA extraction, as well as DNA purification followed by
      hybridization probe-based real-time PCR analysis. An accurate comparability was
      achieved, because both methods analyzed the same preenrichment. The evaluation
      was carried out using both artificially and naturally contaminated meat samples.
      The IMS-real-time PCR assay provides a result after 12 to 13 h. Compared with the
      reference method and regarding artificially contaminated meat samples, the IMS
      real-time PCR assay achieved a specificity of 80% (false-positive rate of 20%)
      and a sensitivity of 100% (false-negative rate of 0%). The relative accuracy was
      94%. The detection limit of both methods was 10 CFU/25 g. The concordance index
      kappa, which defines the statistical accordance, was 0.85 and indicated the
      agreement of both methods on statistical criteria. Compared to the reference
      method and analyzing naturally contaminated meat samples (n = 491), the IMS-real
      time PCR assay showed a specificity of 99.3% (false-positive rate of 0.7%) and a
      sensitivity of 83.7% (false-negative rate of 16.3%). The relative accuracy was
      98%. The concordance index kappa had a value of 0.87 and highlighted the
      statistical agreement of both methods. In conclusion, the IMS-real-time PCR assay
      is suitable as specific, sensitive, and rapid screening method for the detection
      of Salmonella from meat.

PMID- 17186657
TI  - Distribution of Campylobacter genotypes on broilers during slaughter.
AB  - The highly discriminatory genotyping methods now available for Campylobacter have
      enabled investigation of the diversity, origin, and route of transmission of this
      organism. In this study, we investigated the frequency of several genotypes of
      Campylobacter on chicken carcasses postchilling and on neck skin and cloacal
      swabs taken at slaughter. Campylobacter isolates recovered with and without
      enrichment from carcasses were subtyped by macrorestriction profiling. Subtyping
      199 Campylobacter isolates from 36 carcasses revealed an average of 1.5 genotypes
      per carcass. The genotypes present on carcasses were, in most cases, also found
      in the cloacal samples taken at the beginning of the slaughter process. However,
      genotypes present on carcasses were, in some cases, not found in the
      corresponding cloacal samples but in cloacal samples of the preceding slaughter
      group and, in one case, from the preceding day. The genotypes present in cloacal
      samples were, with one exception, also found on the corresponding carcasses,
      indicating that most genotypes survive processing. In most cases, there was a
      difference of several bands between genotypes present in the same slaughter
      group, indicating different origins of the isolates rather than the occurrence of
      a recombination event. However, in two cases, a recombination event could have
      generated the difference in band patterns seen for two pairs of isolates with
      nearly identical band patterns, even after cleavage with a second restriction
      enzyme. The results indicate that individual Campylobacter-positive Swedish
      chicken carcasses, as well as whole carcass groups, are, in general, contaminated
      by one or two different genotypes.

PMID- 17186658
TI  - A longitudinal study of Salmonella and Campylobacter jejuni isolates from day of
      hatch through processing by automated ribotyping.
AB  - Comparisons of bacterial populations over long periods of time allow researchers
      to identify clonal populations, perhaps those responsible for contamination of
      farms or humans. Salmonella and Campylobacter can cause human illness, and our
      objective was to use a library typing system to track strains that persist in the
      poultry house and through the processing plant. Two farms, over four consecutive
      flocks, were studied. Multiple samples were taken of the poultry house
      environment, feed mill, transport crates, and carcasses in the processing plant.
      Sample collection on the farm took place on chick placement day, midgrowout, and
      the day of harvest. This study found that 80.3% of isolates belonged to a single
      strain of Salmonella Kentucky that persisted in several environmental samples for
      all flocks at both farms, from chick placement day to the final product at the
      plant. Surgical shoe covers produced most isolates (n = 26), and processing day
      yielded the highest recovery (n = 68). Additional serotypes were recovered, but
      the Salmonella Kentucky-positive eggshells and chick mortality appeared to be the
      source of the organism for both farms. All Campylobacter isolates recovered were
      identified as C. jejuni. Most Campylobacter isolates (90.1%) belonged to one of
      three core strains. C. jejuni was not recovered on chick placement day. Cecal
      droppings yielded all nine strains. Most isolates (98.2%) were from one farm.
      Cluster analysis grouped C. jejuni and Salmonella isolates into four and six
      distinct clusters, respectively, on the basis of a similarity level of 80%.

PMID- 17186659
TI  - Prevalence and antimicrobial resistance of Campylobacter jejuni and Campylobacter
      coli isolated from raw chicken meat and human stools in Korea.
AB  - Prevalence of Campylobacter in raw chicken meat and human stools and subsequent
      antibiotic resistance profiles of the pathogenic isolates obtained from 2000
      through 2002 were investigated. Campylobacter jejuni and Campylobacter coli were
      isolated from 570 of the 923 raw chicken meat samples collected from traditional
      markets, large retail stores, or department stores in Korea, resulting in the
      isolation rate of 61.8%. A total of 579 Campylobacter isolates were obtained from
      raw chicken (36.3% for C. jejuni and 26.4% for C. coli) with the average
      population of 335.6 CFU/g. From 513 human stool samples, 15 isolates of
      Campylobacter were detected. Seasonal variation in the quantification of C. coli
      was not noticeable throughout the year, while the isolation rate of C. jejuni was
      the highest in September through October (840 CFU/g) followed by that of July
      through August and May through June in decreasing order, showing a significant
      seasonal effect (P < 0.05). Contamination of Campylobacter was more severe in raw
      chicken meat sold in traditional markets than in those sold in large retail
      stores and department stores. Prevalence of Campylobacter in raw chicken sold in
      traditional markets was significantly influenced by seasonal changes (P < 0.05),
      whereas the samples obtained from other places was less affected by the seasonal
      changes. Susceptibilities of the 594 chicken isolates to ciprofloxaxin,
      chloramphenicol, erythromycin, kanamycin, nalidixic acid, and tetracycline were
      determined by an E-test. Campylobacter isolates were the most resistant to
      nalidixic acid (91.4%) followed by ciprofloxaxin (87.9%), tetracycline (87.2%),
      kanamycin (30.6%), erythromycin (19.4%), and chloramphenicol (1.3%). Human
      isolates showed a similar resistance to the six antibiotics tested. The
      proportion of Campylobacter isolates with multidrug resistance to four or more
      antimicrobials obtained from 2000 through 2002 ranged from 28 to 43.5%,
      indicating that it could be a serious health-threatening factor. This study
      suggests that it is prudent to establish an effective National Monitoring Program
      in Korea for the prevention and control of Campylobacter spp.

PMID- 17186660
TI  - Susceptibility of the heat-, acid-, and bile-adapted Vibrio vulnificus to lethal
      low-salinity stress.
AB  - As a marine pathogenic bacterium that inhabits seawater or seafood, Vibrio
      vulnificus encounters low salinity and other stresses in the natural environment
      and during food processing. This investigation explores the cross-protective
      response of sublethal heat-, acid-, or bile-adapted V. vulnificus YJ03 against
      lethal low-salinity stress. Experimental results reveal that the acid (pH 4.4)-
      and heat (41 degrees C)-adapted V. vulnificus were not cross-protected against
      the lethal low-salinity challenge (0.04% NaCl). The bile (0.05%)-adapted
      exponential- and stationary-phase cells were cross-protected against low
      salinity, whereas low-salinity (0.12% NaCl)-adapted stationary cells were
      sensitized against 12% bile stress. Results of this study provide further insight
      into the interaction between low salinity and other common stresses in V.
      vulnificus.

PMID- 17186661
TI  - International Life Sciences Institute North America Listeria monocytogenes strain
      collection: development of standard Listeria monocytogenes strain sets for
      research and validation studies.
AB  - Research and development efforts on bacterial foodborne pathogens, including the
      development of novel detection and subtyping methods, as well as validation
      studies for intervention strategies can greatly be enhanced through the
      availability and use of standardized strain collections. These types of strain
      collections are available for some foodborne pathogens, such as Salmonella and
      Escherichia coli. We have developed a standard Listeria monocytogenes strain
      collection that has not been previously available. The strain collection includes
      (i) a diversity set of 25 isolates chosen to represent a genetically diverse set
      of L. monocytogenes isolates as well as a single hemolytic Listeria innocua
      strain and (ii) an outbreak set, which includes 21 human and food isolates from
      nine major human listeriosis outbreaks that occurred between 1981 and 2002. The
      diversity set represents all three genetic L. monocytogenes lineages (I, n = 9;
      II, n = 9; and III, n = 6) as well as nine different serotypes. Molecular
      subtyping by EcoRI automated ribotyping and pulsed-field gel electrophoresis
      (PFGE) with AscI and ApaI separated the 25 isolates in the diversity set into 23
      ribotypes and 25 PFGE types, confirming that this isolate set represents
      considerable genetic diversity. Molecular subtyping of isolates in the outbreak
      set confirmed that human and food isolates were identical by ribotype and PFGE,
      except for human and food isolates for two outbreaks, which displayed related but
      distinct PFGE patterns. Subtype and source data for all isolates in this strain
      collection are available on the Internet and are linked to the PathogenTracker
      database (www.pathogentracker.com), which allows the addition of new, relevant
      information on these isolates, including links to publications that have used
      isolates from this collection. We have thus developed a core L. monocytogenes
      strain collection, which will provide a resource for L. monocytogenes research
      and development efforts with centralized Internet-based data curation and
      integration.

PMID- 17186662
TI  - Transfer of Listeria monocytogenes during slicing of turkey breast, bologna, and
      salami with simulated kitchen knives.
AB  - In response to continued concerns regarding Listeria cross-contamination during
      the slicing of deli meats, a series of specially prepared grade 304 and 316
      stainless steel kitchen knife blades was inoculated with a six-strain Listeria
      monocytogenes cocktail (10(8), 10(5), and 10(3) CFU per blade) composed of two
      weak, two medium, and two strong biofilm-forming strains. The blades were then
      attached to an Instron 5565 electromechanical compression analyzer and used to
      slice whole chubs of delicatessen turkey breast, bologna, and salami to entirety
      (30 slices) at a cutting speed of 8.3 mm/s. Homogenates of the slices in
      University of Vermont Medium were surface or pour plated with modified Oxford
      agar and then enriched. Listeria transfer from knife blades inoculated at 10(8)
      CFU per blade was logarithmic, with a 2-log decrease seen after 8 to 12 slices
      and direct counts obtained thereafter out to 30 slices. However, blades
      containing 10(5) and 10(3) CFU per blade typically yielded direct counts out to
      only 20 and 5 slices, respectively. Normalizing data on a log scale for the first
      10 slices resulted in significantly greater Listeria transfer and "tailing" from
      grade 304 as opposed to grade 316 stainless (P < 0.05) for all three products.
      After 1 year of use, surface roughness values as determined by surface
      profilometry were significantly greater (P < 0.001) for grade 304 than for grade
      316 stainless blades. Cutting force and blade sharpness were not significantly
      different (P > 0.05) within stainless steel grade (P < 0.05) for each product.
      However, significant differences in cutting force were seen between salami and
      turkey (P < 0.05) for grades 304 and 316 stainless, respectively. In addition to
      compositional differences in the deli meats and knife blades, wear and scoring on
      the blade likely affected Listeria transfer during slicing.

PMID- 17186663
TI  - Inhibition and inactivation of Listeria monocytogenes and Escherichia coli
      O157:H7 colony biofilms by micellar-encapsulated eugenol and carvacrol.
AB  - The antimicrobial efficacy of carvacrol and eugenol, two essential oil compounds,
      encapsulated in a micellar nonionic surfactant solution on four strains of
      Listeria monocytogenes (Scott A, 101, 108, and 310) and four strains of
      Escherichia coli O157:H7 (H1730, E0019, F4546, and 932) growing as colony
      biofilms was investigated. Carvacrol and eugenol were encapsulated in Surfynol
      485W at concentrations ranging from 0.3 to 0.9% (wt/wt) at a surfactant
      concentration of 5% (wt/wt). Colony biofilms were grown on polycarbonate
      membranes resting on agar plates containing antimicrobial formulations. Cells
      were enumerated after 0, 3, 6, 9, 24, 48, and 72 h of incubation. Colony biofilms
      of all E. coli O157:H7 strains were more sensitive to both antimicrobial systems
      than L. monocytogenes strains. Surface-grown E. coli O157:H7 viable cell numbers
      decreased below detectable levels after exposure to encapsulated essential oil
      compounds for > 3 h at all tested concentrations, except for E. coli O157:H7
      F4546, which grew slowly in the presence of < 0.5% (wt/wt) eugenol. L.
      monocytogenes Scott A and 101 were more resistant to eugenol than carvacrol at
      sublethal concentrations (< 0.5% [wt/wt]). Carvacrol was effective at any
      concentration against L. monocytogenes 108, whereas concentrations of > 0.5%
      (wt/wt) eugenol were required for inactivation. L. monocytogenes 310 was equally
      sensitive to both essential oil compounds. Results suggest that surfactant
      encapsulated generally recognized as safe essential oil compounds may offer a new
      means to control the growth of food pathogens such as E. coli O157:H7 and L.
      monocytogenes on food contact surfaces.

PMID- 17186664
TI  - Irradiation inactivation of Listeria monocytogenes in low-fat ground pork at
      freezing and refrigeration temperatures.
AB  - Gamma radiation effectively controls Listeria monocytogenes in uncooked and in
      ready-to-eat foods. This study was conducted to determine if gamma radiation
      could be used to control L. monocytogenes in ground pork. Ground pork was
      contaminated with L. monocytogenes, kept at refrigeration (4 degrees C), chilling
      (0 degrees C), and freezing (-18 degrees C) temperatures overnight, exposed to
      gamma radiation and stored at 4 degrees C for 7 days, and at 0 and -18 degrees C
      for 60 days. Following irradiation, the meat was assayed for L. monocytogenes
      viable counts and lipid oxidation. A triangle test was performed to determine if
      sausage made from the irradiated and nonirradiated ground pork differed in
      sensory quality. It was observed that a 5-log reduction of L. monocytogenes
      viable counts would require a 3.0-kGy radiation dose. The results of a 60-day
      storage study of ground pork inoculated with 10(5) to 10(6) CFU of L.
      monocytogenes per gram indicated that counts for nonirradiated meat remained
      fairly constant at refrigeration, chilling, and freezing temperatures. However,
      irradiation of ground pork at 3.0 kGy could inactivate L. monocytogenes totally
      in ground pork subsequently held at all the temperatures used in this study.
      Lipid oxidation measurements, as determined by the thiobarbituric acid-reactive
      substance assay, ranged from 0.16 nmol/g for nonirradiated ground pork and 0.20
      nmol/g for meat irradiated at 3.0 kGy. Sensory panelists could distinguish
      between irradiated and nonirradiated sausage but were divided on whether
      irradiation adversely affected the sausage quality. Our results suggest that
      gamma radiation could be useful to control L. monocytogenes in ground pork and
      improve the safety of ground pork products.

PMID- 17186665
TI  - Effect of gamma radiation and oregano essential oil on murein and ATP
      concentration of Listeria monocytogenes.
AB  - The effects of gamma radiation and of oregano essential oil alone or in
      combination with radiation on murein composition of Listeria monocytogenes and on
      the intracellular and extracellular concentration of ATP were evaluated. The
      bacterial strain was treated with two radiation doses, 1.2 kGy to induce cell
      damage and 3.5 kGy to cause cell death. Oregano essential oil was used at 0.020
      and 0.025% (wt/vol), which is the MIC. All treatments had a significant effect (P
      < or = 0.05) on the murein composition, although some muropeptides did not seem
      to be affected by the treatment. Each treatment influenced differently the
      relative percentage and number of muropeptides. There was a significant
      correlation (P < or = 0.05) between the reduction of intracellular ATP and
      increase in extracellular ATP, following treatment of the cells with oregano oil.
      The reduction of intracellular ATP was even more important when essential oil was
      combined with irradiation, but irradiation of L. monocytogenes alone induced a
      significant decrease (P < or = 0.05) of the internal ATP without affecting the
      external ATP. Transmission electron microscopic observation revealed that oregano
      oil and irradiation have an effect on cell wall structure.

PMID- 17186666
TI  - Automated ribotyping for the identification and characterization of foodborne
      clostridia.
AB  - The DuPont Qualicon RiboPrinter was employed to determine if automated ribotyping
      could be used to differentiate between and characterize various species of
      foodborne clostridia. EcoRI digests were used to ribotype 49 isolates that
      represented seven Clostridium species: C. aerotolerans, C. beirjerinckii, C.
      botulinum, C. butyricum, C. perfringens, C. putrificum, and C. sporogenes. EcoRV
      digests were also used to ribotype 17 C. botulinum isolates to determine if an
      alternate restriction enzyme was more suitable than was EcoRI for toxin typing.
      It was concluded that the RiboPrinter could be potentially used to identify most
      of the clostridia represented in the study, but that the system has difficulty
      distinguishing between C. botulinum and C. sporogenes. The system may also be
      potentially used to characterize clostridia based on phenotypic characteristics.
      Toxin typing of clostridia remains problematic, but may be improved by the use of
      restriction enzyme combinations.

PMID- 17186667
TI  - Prevalence and antimicrobial resistance of enterococci isolated from retail
      fruits, vegetables, and meats.
AB  - Although enterococci are considered opportunistic pathogens, they can be
      reservoirs of antimicrobial resistance. Antimicrobial resistance is increasingly
      important because of foodborne illnesses from meat and infections from produce.
      From 2000 through 2001, food items (vegetables, fruits, and meats) were obtained
      from grocery store chains in northern Georgia and cultured for the presence of
      enterococci; 47.7% (189 of 396) of these samples were positive for enterococci.
      For the fruits and vegetables, enterococci were cultured most often from tomatoes
      (9 of 27 samples, 33%) and radishes (10 of 11 samples, 91%), respectively. Among
      the meat items tested, enterococci were isolated from 95% (21 of 22) of the
      chicken samples, 73% (16 of 22) of the beef samples, 95% (20 of 21) of the turkey
      samples, and 68% (15 of 22) of the pork samples. The predominant species
      identified was Enterococcus faecalis (n = 80) from meat and Enterococcus
      casseliflavus (n = 66) from fruits and vegetables. Although high numbers of
      isolates were resistant to lincomycin (176 of 185 isolates, 95.1%) and bacitracin
      (150 of 185 isolates, 81.1%), very few isolates were resistant to salinomycin (2
      isolates, 1.1%), penicillin (3 isolates, 1.6%), or nitrofurantoin (9 isolates,
      4.9%). None of the isolates were resistant to linezolid or vancomycin. These data
      suggest that foods commonly purchased from grocery stores are a source of
      enterococci; however, overall resistance to antimicrobials is relatively low.

PMID- 17186668
TI  - Nonstarter lactobacilli isolated from soft and semihard Argentinean cheeses:
      genetic characterization and resistance to biological barriers.
AB  - Nonstarter lactic acid bacteria isolated from Argentinean cheeses were identified
      and characterized by focusing on their resistance to biological barriers, along
      with other physiological features of potential interest, in the search for future
      probiotic organisms. Lactobacilli were enumerated and isolated from semihard and
      soft cheeses made with multistrain Streptococcus thermophilus starters.
      Lactobacilli counts in 1-week-old cheeses were between 10(5) and 10(7) CFU/g and
      then reached 10(7) CFU/ g in all 1-month samples, while streptococci were always
      above 10(9) CFU/g. A total number of 22 lactobacilli isolates were retained,
      identified, and characterized by in vitro tests. Species identity was determined
      by carbohydrate metabolism and species-specific PCR assays. Genetic diversity was
      explored by random amplified polymorphic DNA (RAPD) PCR analysis. The
      Lactobacillus strains were assigned to the species L. casei, L. plantarum, L.
      rhamnosus, L. curvatus, L. fermentum, and L. perolens. All the strains studied
      tolerated 25 ppm of lysozyme, and most of them showed resistance to 0.3% bile.
      After incubation in gastric solution (pH 2.0), counts decreased by several log
      units, ranging from 3.2 to 7.0. The strains were able to grow in the presence of
      bile salts, but only three isolates were capable of deconjugation. The nonstarter
      lactobacilli that were assayed fermented the prebiotic substrates (especially
      lactulose and inulin). Some strains showed high cell hydrophobicity and beta
      galactosidase activity, as well as inhibitory activity against pathogenic
      bacteria. It was concluded that most of the lactobacilli isolated in this study
      demonstrated resistance to biological barriers and physiological characteristics
      compatible with probiotic properties, which make them suitable for further
      research in in vivo studies aimed at identifying new probiotic organisms.

PMID- 17186669
TI  - Identification of antibacterial peptides from bovine kappa-casein.
AB  - The objective of the present study was to identify antimicrobial peptides present
      in several digests of commercial caseins with gastric enzymes. The most active
      hydrolysate against Escherichia coli ATCC 25922 and Listeria innocua CECT 910T
      corresponded to a pepsin digest of bovine kappa-casein. The protein digest was
      first separated by semipreparative high-performance liquid chromatography (HPLC),
      and the most active fractions were again subjected to a second chromatographic
      step. Finally, identification of the active peptides was carried out by online
      and offline HPLC-electrospray ionization-tandem mass spectrometry. By means of
      this technique, 21 peptides were identified in the active HPLC fractions.
      Although most were derived from bovine kappa-casein, some of the identified
      fragments corresponded to beta-casein and alpha(s)-casein fragments, a result of
      the presence of small amounts of these proteins in the preparation of kappa
      casein. Some of the peptides identified were chemically synthesized and showed
      antibacterial effects against several gram-positive and gram-negative bacteria.
      Among the synthesized peptides, kappa-casein f(18-24), f(30-32), and f(139-146)
      were most effective against all bacteria tested. The antibacterial effect of
      these peptides is discussed in relation to their amino acid sequences.

PMID- 17186670
TI  - Reevaluation of antimicrobial and antioxidant activity of Thymus spp. extracts
      before and after encapsulation in liposomes.
AB  - The antioxidant and antimicrobial activity of four Thymus species (boissieri,
      longicaulis, leucospermus, and ocheus) extracts were determined. Two methods
      (Rancimat and malondialdehyde by high-performance liquid chromatography) were
      used to measure the antioxidant action in comparison with common commercial
      antioxidants, including butylated hydroxytoluene and alpha-tocopherol. The
      extracts that presented high antioxidant activity were encapsulated in liposomes
      and their antioxidant action was again estimated. Thermal-oxidative decomposition
      of the samples (pure liposomes and encapsulating extracts) was studied using the
      differential scanning calorimetry method. The modification of the main transition
      temperature for the lipid mixture and the splitting of the calorimetric peak in
      the presence of the antioxidants were also demonstrated by differential scanning
      calorimetry. All extracts showed antioxidant and antimicrobial activities. Some
      extracts showed superior or equal antioxidant activity to alpha-tocopherol. When
      the extracts were encapsulated in liposomes, their antioxidant as well as
      antimicrobial activities proved to be superior from the same extracts in pure
      form.

PMID- 17186671
TI  - Biogenic amines in natural ciders.
AB  - Biogenic amines play an important physiological role in mammals, and high amounts
      of some exogenous amines in human diet may contribute to a wide variety of toxic
      effects. These amines are commonly found in many foodstuffs, particularly in
      fermented products such as cheese, meat products, beer, wine, and ciders. Here,
      the level of biogenic amines in some natural ciders was examined. Twenty-four
      samples of cider purchased from commercial sources were analyzed by reverse-phase
      high-performance liquid chromatography and fluorescence detection after precolumn
      derivatization with o-phthaldialdehyde. Amine levels were variable, ranging from
      not detected to 23 mg/liter. The average level of total biogenic amines in ciders
      was 5.94 +/- 8.42 mg/liter. Putrescine, histamine, and tyramine were the
      prevailing amines being present in 50.0, 37.5, and 33.3% of the ciders studied;
      very small amounts of ethylamine and phenylethylamine were observed in only one
      sample. Other cider parameters were analyzed to determine whether they affect the
      biogenic amine content in ciders, and the results were evaluated by applying
      cluster analysis and principal component analysis. Ciders that showed lower
      glycerol contents and higher amounts of 1,3-propanediol had much higher levels of
      histamine, tyramine, and putrescine, suggesting a high activity of lactic acid
      bacteria during cider making and thus the need for effective control of lactic
      acid bacteria.

PMID- 17186672
TI  - Enterobacteriaceae in dehydrated powdered infant formula manufactured in
      Indonesia and Malaysia.
AB  - To determine the occurrence of Salmonella and Shigella in infant formula from
      Southeast Asia, 74 packages of dehydrated powdered infant follow-on formula
      (recommended age, > 4 months) from five different manufacturers, four from
      Indonesia and one from Malaysia, were analyzed. None of the 25-g test portions
      yielded Salmonella or Shigella. However, further identification of colonies
      growing on selective media used for Salmonella and Shigella detection revealed
      the frequent occurrence of several other Enterobacteriaceae species. A total of
      35 samples (47%) were positive for Enterobacteriaceae. Ten samples (13.5%) from
      two Indonesian manufacturers yielded Enterobacter sakazakii. Other
      Enterobacteriaceae isolated included Pantoea spp. (n = 12), Escherichia hermanii
      (n = 10), Enterobacter cloacae (n = 8), Klebsiella pneumoniae subsp. pneumoniae
      (n = 3), Citrobacter spp. (n = 2), Serratia spp. (n = 2), and Escherichia coli (n
      = 2). To our knowledge, this is the first report to describe the contamination of
      dehydrated powdered infant formula from Indonesia with E. sakazakii and several
      other Enterobacteriaceae that could be opportunistic pathogens. Improper
      preparation and conservation of these products could result in a health risk for
      infants in Indonesia.

PMID- 17186673
TI  - Seasonal prevalence of Escherichia coli O157:H7 in beef cattle feces.
AB  - Cattle are an asymptomatic reservoir of Escherichia coli O157:H7, but the
      bacterial colonization and shedding patterns are poorly understood. The
      prevalence and shedding of this human pathogen have been reported to be seasonal
      with rates typically increasing during warm months. The objectives of this study
      were (i) to assess the prevalence of E. coli O157:H7 in feces of feedlot cattle
      in Kansas during summer, fall, and winter months, and (ii) to characterize E.
      coli O157:H7 by screening for virulence factors. Of 891 fecal samples collected,
      82 (9.2%) were positive for E. coli O157:H7. No significant differences in
      prevalence were detected among summer, fall, and winter months. The highest
      monthly prevalence (18.1%) was detected in February. All tested isolates were
      positive for stx2 (Shiga toxin 2) and eaeA (intimin) genes; 14 isolates (12.8%)
      also carried stx1. Our results indicate the prevalence of E. coli O157:H7 in beef
      cattle feces is not necessarily season dependent.

PMID- 17186674
TI  - Investigation of Campylobacter in reared game birds.
AB  - A total of 103 pooled samples of neck skin and meat from pigeons for the table
      and neck skin of pheasant were analyzed bacteriologically to determine the
      presence of Campylobacter. Colonies suspected of being Campylobacter were grown
      from 15.8% of pigeon neck skin samples, 12.5% of pigeon meat samples, and 50% of
      pheasant neck skin samples after culturing, and in 6.9% of pigeon neck skin
      samples (4 x 10(2) to 2 x 10(3) CFU/g) assessed quantitatively without
      preculturing. PCR confirmed the presence of Campylobacter spp. in 5.26 and 3.44%
      of samples of pigeon neck skin and meat, respectively. Species identified from
      pigeon neck skin samples by PCR were C. jejuni (3 of 3) and C. coli (1 of 3); no
      C. lari was identified. No species were identified by PCR in pheasant neck skin.
      We conclude that the small number of Campylobacter-positive pigeon samples
      presents a low risk of Campylobacter infection to Italian consumers, particularly
      since pigeon is always well cooked before consumption, although there is always
      the possibility of cross-contamination with raw or insufficiently cooked foods
      particularly during food preparation.

PMID- 17186675
TI  - Heat inactivation of Listeria monocytogenes and Salmonella enterica serovar Typhi
      in a typical bologna matrix during an industrial cooking-cooling cycle.
AB  - The heat resistance of Salmonella enterica serovar Typhi PF-724 and Listeria
      monocytogenes 2812 was determined in a commercial bologna batter. The heat
      inactivation of the two bacterial species was also studied in a semiautomatic
      pilot smokehouse under cooking conditions that reproduced an industrial bologna
      process. S. enterica serovar Typhi PF-724 was less heat resistant than L.
      monocytogenes 2812. The D-values (times required to reduce the population by 1
      logarithmic cycle) for S. enterica serovar Typhi PF-724 ranged from 10.11 to 0.04
      min for temperatures of 50 to 70 degrees C, while for L. monocytogenes 2812, the
      D-values were 2.5-, 4.9-, 3.8-, 3.3-, and 2-fold higher at 50, 55, 60, 65, and 70
      degrees C, respectively, than for S. enterica serovar Typhi PF-724. However, the
      z-value (temperature required to reduce log D by 1 logarithmic cycle) for S.
      enterica serovar Typhi PF-724 (5.72 degrees C) was not significantly different
      from the z-value for L. monocytogenes 2812 (7.04 degrees C), indicating that a
      given increase in temperature would have a similar effect on the decimal
      reduction time for both bacterial species in that meat emulsion. Our data on
      experimentally inoculated batter also showed that processing bologna at a cooking
      cooling cycle commonly used in the industry resulted in a minimum 5-log reduction
      for both S. enterica serovar Typhi PF-724 and L. monocytogenes 2812.

PMID- 17186676
TI  - Role of uvrA in the growth and survival of Listeria monocytogenes under UV
      radiation and acid and bile stress.
AB  - Listeria monocytogenes encounters numerous stresses both in the food environment
      and during infection of the host. The ability to survive and tolerate bile and
      low pH conditions, which are two major stresses, is of particular importance for
      survival within the host. The uvrA gene in other bacteria is involved in the
      repair of acid-induced DNA damage and in adaptation to low pH. Thus, a uvrA in
      frame deletion mutant was constructed to identify the role of uvrA in the growth
      and survival of L. monocytogenes under various environmental conditions. The uvrA
      mutant was highly sensitive to UV radiation. Growth under normal laboratory
      conditions was impaired during the exponential phase, and the time to reach the
      exponential phase of growth, TV(max), was significantly delayed (P < 0.05).
      Growth of the uvrA mutant in acidic medium (pH 5) was slightly impaired, and the
      TV(max) was significantly delayed (P < 0.05). Growth and the TV(max) of the
      mutant in the presence of 0.3% bile salts also were significantly impaired (P <
      0.05). These results suggest that uvrA is needed for optimal growth and survival
      of L. monocytogenes under various stressful environmental conditions.

PMID- 17186677
TI  - Survival and growth of foodborne pathogens during cooking and storage of oriental
      style rice cakes.
AB  - Fresh cooked rice cakes for retail sale are typically held at room temperature
      because refrigeration dramatically reduces their quality. Room temperature, high
      water activity, and a pH of > 4.6 provided an environment conducive to pathogen
      growth. To date, no studies have been published regarding survival and growth of
      foodborne pathogens in fresh cooked rice cakes. This study was undertaken to
      investigate the effect of steam cooking on foodborne pathogens and their
      subsequent growth in five varieties of rice cakes made from flours of regular
      rice, sweet rice, white rice, tapioca, and mung bean. Bacillus cereus spores were
      detected in white rice, tapioca, and mung bean samples. The rice cake flours were
      inoculated with non-spore-forming foodborne pathogens (Escherichia coli O157:H7,
      Salmonella enterica serovar Typhimurium, Listeria monocytogenes, and
      Staphylococcus aureus) or spore-forming bacteria (Bacillus cereus) and steam
      cooked (100 degrees C) for 30 min. Steam cooking significantly reduced (> 6 log
      CFU/g) non-spore-forming foodborne pathogens in all samples and inactivated
      spores of B. cereus by 1 to 2 log CFU/g. Although spores of B. cereus survived
      steam cooking and germinated during 3 days of storage at room temperature,
      populations in most rice cakes remained below 106 CFU/g, which is the threshold
      for producing toxin. Rice cakes made from mung bean flour supported growth and
      germination of B. cereus spores above that critical level. In mung bean rice
      cakes, enterotoxin production was detected by the second day, when B cereus cell
      populations reached about 6.9 log CFU/g. The toxin concentration increased with
      storage time. However, our results suggest that rapid growth of total mesophilic
      microorganisms by more than 7 to 8 log CFU/ml during the first day of storage
      produced off flavors and spoilage before B. cereus was able to grow enough to
      produce toxins. Therefore, steam-cooked rice cakes made from a variety of flours
      including mung bean flour are safe for sale for up to 1 day after storage at room
      temperature and are free of B. cereus toxins.

PMID- 17186678
TI  - Bacteriological quality of drinking water from dispensers (coolers) and possible
      control measures.
AB  - Three water dispensers (coolers) were bacteriologically monitored over a period
      of 3 months to evaluate their hygienic status. For this purpose, 174 samples of
      chilled and unchilled water were analyzed for levels of mesophilic aerobic
      bacteria and the presence of Escherichia coli and enterococci in 100-ml samples,
      and the presence of Pseudomonas aeruginosa in 10- and 100-ml samples.
      Additionally, 12 samples from 20-liter plastic bottles of spring water used to
      supply the coolers and 36 samples of 12 different brands of noncarbonated bottled
      mineral water were similarly analyzed. Water from the coolers yielded aerobic
      plate counts of 3 to 5 log CFU/ml with a geometric mean of 3.86 log CFU/ml,
      whereas water from the 20-liter bottles had a mean aerobic plate count of 3.3 log
      CFU/ml. Aerobic plate counts for noncarbonated mineral waters were generally
      lower (13 samples, < 10 CFU/ml; 6 samples, 10 to 10(2) CFU/ml; 13 samples, 10(2)
      to 10(3) CFU/ml; 3 samples, 10(3) to 10(4) CFU/ ml; 1 sample, 2 x 10(4) CFU/ml).
      Although occasional professional cleaning of the coolers did not affect the
      aerobic plate count, P. aeruginosa was successfully eliminated 2 weeks after
      cleaning, with only one cooler becoming recolonized. Neither E. coli nor
      enterococci was found in any of the water samples tested. However, P. aeruginosa
      was identified in three (25%) of twelve 100-ml samples from 20-liter bottles of
      spring water; a similar frequency of 24.1% was seen for water samples from
      coolers. Overall, 35 (21.6%) of 162 water samples (10 ml) from coolers also
      yielded P. aeruginosa, suggesting potential growth of P. aeruginosa in the
      dispensers. Pulsed-field gel electrophoresis typing and antibiotic susceptibility
      testing found 19 P. aeruginosa isolates from the coolers and bottles to be
      identical, indicating that a single strain originated from the bottled water
      rather than the surroundings of the coolers. Because P. aeruginosa can cause
      serious nosocomial infections, its spread should be strictly controlled in
      institutions caring for vulnerable people such as hospitals and nursing homes.
      Consequently, in keeping with legal requirement for bottled spring and mineral
      water in Switzerland, it is also advisable that P. aeruginosa be absent in 100-ml
      samples of cooler water.

PMID- 17186679
TI  - Multiplexed detection of mycotoxins in foods with a regenerable array.
AB  - The occurrence of different mycotoxins in cereal products calls for the
      development of a rapid, sensitive, and reliable detection method that is capable
      of analyzing samples for multiple toxins simultaneously. In this study, we report
      the development and application of a multiplexed competitive assay for the
      simultaneous detection of ochratoxin A (OTA) and deoxynivalenol (DON) in spiked
      barley, cornmeal, and wheat, as well as in naturally contaminated maize samples.
      Fluoroimmunoassays were performed with the Naval Research Laboratory array
      biosensor, by both a manual and an automated version of the system. This system
      employs evanescent-wave fluorescence excitation to probe binding events as they
      occur on the surface of a waveguide. Methanolic extracts of the samples were
      diluted threefold with buffer containing a mixture of fluorescent antibodies and
      were then passed over the arrays of mycotoxins immobilized on a waveguide.
      Fluorescent signals of the surface-bound antibody-antigen complexes decreased
      with increasing concentrations of free mycotoxins in the extract. After sample
      analysis was completed, surfaces were regenerated with 6 M guanidine
      hydrochloride in 50 mM glycine, pH 2.0. The limits of detection determined by the
      manual biosensor system were as follows: 1, 180, and 65 ng/g for DON and 1, 60,
      and 85 ng/g for OTA in cornmeal, wheat, and barley, respectively. The limits of
      detection in cornmeal determined with the automated array biosensor were 15 and
      150 ng/g for OTA and DON, respectively.

PMID- 17186680
TI  - Importance of modulating the renin-angiotensin system in preventing renal
      complications of hypertension.
AB  - Chronic kidney disease (CKD) is a major problem worldwide. It threatens the lives
      and health of many people and places severe financial burdens on health economies
      of even the wealthiest countries. It is clear that the approach to prevention is
      multifaceted including prevention of cardiovascular disease. Inhibitors of the
      RAS are the drugs of initial choice in preventing progressive CKD, and may be
      used cautiously in advanced renal insufficiency. In addition blood pressure must
      be optimally controlled to < 130/80 mm Hg. Treatment of late CKD results only in
      a risk reduction and not a prevention of end stage renal disease. It is vital
      that patients at risk for CKD should be identified early before overt renal
      damage. Screening for microalbuminuria in patients with hypertension, metabolic
      syndrome and diabetes is particularly important.

PMID- 17186681
TI  - Diabetic nephropathy.
AB  - In most Western countries, diabetic nephropathy (DN) has become the single most
      common condition found in patients with end-stage renal disease (ESRD). This is
      to some extent due to better survival of diabetic patients with renal failure,
      but mostly due to the dramatic increase in the prevalence of type 2 diabetes. The
      majority of type 2 diabetic patients with renal failure suffer from nodular
      glomerulosclerosis (Kimmelstiel-Wilson); but ischemic nephropathy, irreversible
      acute renal failure (mostly acute on chronic) and diabetes co-existing with
      primary renal diseases are common as well. Classical DN evolves in a sequence of
      stages. After a period of glomerular hyperfiltration, increased urinary albumin
      excretion [microalbuminuria (MA)] i.e. 30-300 mg/day or 20 - 200 microg/minute
      indicates the onset of overt DN. Risk factors for development of DN are positive
      family history, hyperglycemia in the mother during pregnancy, high blood
      pressure, obesity and insulin resistance. Poor glycemic control (HbAlc) and
      elevated systolic blood pressure (> 135 mm Hg) interact in enhancing the risk of
      DN. Proteinuria and smoking are major promoters of progression. The risk of onset
      of microalbuminuria can be reduced by lowering of blood pressure and specifically
      by blockade of the renin angiotensin system (RAS). In patients with established
      DN, the target systolic blood pressure should be <130 mm Hg and RAS blockade is
      obligatory. Treating all cardiovascular risk factors is a high priority.
      Antihypertensive management is rendered difficult by extreme volume sensitivity,
      pronounced activation of the RAS and autonomic neuropathy. Cardiac events are
      excessively frequent, glycemic control becomes difficult and autonomic diabetic
      neuropathy with gastroparesis and diabetic foot are additional problems.
      Hemodialysis or continuous ambulatory peritoneal dialysis should be started
      relatively early. In the absence of contraindications, transplantation (renal
      transplantation, combined kidney/pancreas transplantation or pancreas after
      kidney transplantation) is the treatment of choice.

PMID- 17186682
TI  - Knowledge and attitudes of high school students related to organ donation and
      transplantation: a cross-sectional survey in Turkey.
AB  - We have very little information about the knowledge and attitude of high school
      students towards organ donation and transplantation. The aim of this study was to
      identify student-related factors that might affect organ donation, and then use
      this information to develop some essential strategies and policies. Two hundred
      students from one urban high school were surveyed with a questionnaire. After
      completing the first interview, the students underwent a training program on
      organ donation and transplantation. Once this was complete, the students filled
      out the same questionnaire in a second interview session. We then analyzed the
      changes from before to after the educational program in order to assess the
      program's effectiveness. Concerning brain-death, 66.1% of the respondents
      identified the correct definition of this concept before training, and 92% did so
      after training (p<0.001). The correct definition of transplantation was chosen by
      68.3% of the respondents before training, and by 90.6% after training (p<0.001).
      It is clear that this educational program greatly enhanced the students' level of
      knowledge related to many aspects of organ donation and transplantation and
      significantly expanded awareness. By leading to changes in opinion, such training
      programs will significantly increase the number of donors and the rate of
      transplantation in Turkey.

PMID- 17186683
TI  - Cyclosporine utilization in idiopathic nephrotic syndrome in children.
AB  - The treatment of steroid-resistant focal segmental glomerulosclerosis (FSGS)
      imposes one of the most perplexing and frustrating problems on nephrologists.
      Cyclosporine A (CsA) is widely considered as the treatment of choice for steroid
      resistant or dependent nephrotic children. We reviewed the clinical outcome in
      children with idiopathic nephrotic syndrome (INS) under CsA treatment. A total of
      22 children presented with either steroid-resistant nephrotic syndrome (SRNS) (14
      children), or steroid-dependent nephrotic syndrome (SDNS) (8 children) during the
      period from August 2002 to February 2005; the mean age for both groups was 7.6
      years (range: 23months -15 years). Renal histology showed FSGS in 14(63%)
      patients, minimal change disease (MCD) in 4(18%), diffuse mesangial
      glomerulonephritis (MesGN) in three (13.6%), and membranous glomerulonephritis
      (MGN) in two (6.8%). Treatment with CsA in combination with alternate-day
      prednisolone induced remission in 15(68%) patients; 9(60%) patients had complete
      remission and six (40%) had partial remission. Seven (50 %) patients in the SRNS
      group responded to CsA treatment; two (14.2%) patients had complete remission and
      5 (35.7%) had partial remission. Seven (87.5%) children in the SDNS group had
      complete remission and one (13.5%) had partial remission. We conclude that this
      study demonstrates the efficacy of CsA in inducing remission in the steroid
      dependent is higher than in the steroid resistant nephrotic children We believe
      that CsA is probably a good alternative therapy in this population.

PMID- 17186684
TI  - The diagnostic utility of Self-Reporting Questionnaire (SRQ) as a screening tool
      for major depression in hemodialysis patients.
AB  - There is overwhelming evidence that individuals with Major Depressive Disorder
      (MDD) are being seriously under diagnosed and under treated. The Self-Reporting
      Questionnaire (SRQ) is a good screening instrument for the detection of
      psychiatric disorders. However, the clinical significance of SRQ as a screening
      test for MDD in patients on hemodialysis (HD) has yet to be elucidated. The
      purpose of this study was to evaluate the diagnostic utility of the SRQ in
      detecting MDD in a cohort of patients with end-stage renal disease (ESRD) on
      maintenance HD. Twenty-six patients on maintenance HD were randomly recruited and
      were asked to complete the SRQ. The participants were, in addition, interviewed
      by a psychiatrist, who had been blinded to the SRQ score. We examined the ability
      of SRQ to detect patients who were diagnosed to have MDD based on psychiatric
      assessment. Among the 26 patients assessed, four patients were diagnosed to have
      MDD based on current diagnostic criteria. Logistic regression analysis showed
      that SRQ could predict patients with MDD with adjusted odds ratio of 1.9 (CI,
      1.06- 3.42). Being a female was the most important variable for having a high SRQ
      (F=16.9, P=0.0004). The limitations of this study include a relatively small
      sample size and a high rate of somatic symptoms reported in the non-depressed
      population that limited the positive predictive value of the SRQ. Thus, although
      the SRQ has a high sensitivity, the positive predictive value of the SRQ is poor
      at low cut offs. In conclusion, our study suggests that an ideal screening tool
      in patients on HD should have minimal emphasis on the somatic symptoms of MDD.
      Until such a tool is available, clinical assessment remains the best screening
      tool for MDD.

PMID- 17186685
TI  - Retrospective analysis of factors affecting the progression of chronic renal
      failure in adult polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the commonest congenital
      cystic renal disease. Factors such as hypertension, urinary tract infection,
      hematuria, and proteinuria may affect the progression to chronic renal failure in
      ADPKD patients. Therapeutic interventions, such as the use of angiotensin
      converting enzyme inhibitors (ACEI) or diet modification, may impact the natural
      progression of the disease. We aim in this study to review a registry of ADPKD
      patients in order to compare the slow and fast progressors and identify possible
      predictors of progression and interventions that slow the progression of this
      disease. Sheffield Kidney Institute (SKI), one of the largest kidney institutes
      in Northern Europe, has registered a large number of ADPKD patients since 1981.
      SKI's computer network contains a wide range of information on these patients. We
      selected 94 adult polycystic patients from the SKI for retrospective analysis of
      factors affecting progression to chronic renal failure. Patients who doubled
      their s. creatinine in < or = 36 months were considered fast progressors (FP),
      while those who doubled their s. creatinine in > 36 months were regarded as slow
      progressors (SP). There were 70 patients in the FP group and 24 patients in the
      SP group. A third group of 137 patients consisted of non-progressors (NP) who had
      stable s. creatinine levels during the same period. We found that the incidence
      of hypertension, UTI, macroscopic and microscopic hematuria, and overt
      proteinuria in the FP group was higher than in the SP and NP groups. Modification
      of some factors, such as hypertension and UTI, may decrease the rate of the
      deterioration of renal function.

PMID- 17186686
TI  - Analysis of vascular access in hemodialysis patients: a report from a dialysis
      unit in Casablanca.
AB  - Vascular access (VA) for patients needing maintenance hemodialysis (HD) remains a
      major obstacle in the management of patients with end-stage renal disease (ESRD).
      We retrospectively analyzed 190 patients, (92 males and 98 females) who had been
      on HD for a period ranging from 12 to 240 months. Their mean age was 42.8 years
      (range: 13 to 83 years). The study was carried out to analyze the VA, including
      the management of its complications. The cause of renal failure was chronic
      glomerulonephritis in 34.2% and unknown in 30.5% of the study cases. In 164
      patients (86.3%), HD was initiated through a temporary catheter inserted in the
      internal jugular vein. Each patient had, on an average, two catheters inserted
      that lasted for a mean duration of 29 days. All patients had a native
      arteriovenous fistula (AVF) as the permanent VA. A primary radial-cephalic AVF
      was created in 96.3% of the patients. The median period before cannulation was 15
      days. Failure of AVF function occurred in 18.4% of cases while the median
      survival of the primary AVF was 54.8 months. Thrombosis, seen in 26.4% of the
      patients, was the predominant complication, and this event seemed to be causally
      related to prior insertion of temporary catheters. Ten patients had arterio
      venous grafts (AVG) placed due to recurrent thrombosis of the AVF. The AVG was
      brachial-cephalic in five patients. A tunneled cuffed catheter was placed in four
      patients who had no other possible access sites available. These catheters were
      placed in the right internal jugular vein in all of these patients. The success
      of VA in patients on HD requires a multi-disciplinary approach and early referral
      to a vascular surgeon

PMID- 17186688
TI  - The attitude of physicians towards education and rehabilitation of patients on
      chronic dialysis: a questionnaire survey.
AB  - In this study, we aimed to evaluate the attitude of physicians in the Kingdom of
      Saudi Arabia (KSA) towards the education and rehabilitation of chronic dialysis
      patients Questionnaires were sent to 155 physicians working in 148 dialysis
      centers. They included 109 centers (73.6 %) in the Ministry of Health (MOH), 18
      (12.2%) in governmental non-MOH sector and 21 centers (14.2 %) in private
      hospitals that together care for a population of more than 7,900 chronic dialysis
      patients. The study was performed between January and March 2006. Responses were
      received from 141 physicians (90.9%) from 140 (94.5%) dialysis centers. There
      were 134 (97.1%) respondents who believed that the ideal ratio of patients per
      dialysis nurse should be < or = 3, 132 (97.1%) believed that the ideal ratio of
      patients per physician should be < or = 25, 120 (88.9%) believed that the ideal
      ratio of patients per dietitian should be < or = 50, and 102 respondents (81.0%)
      believed that the ideal ratio of patients per social worker should be < or =50.
      There were 46 respondents (32.6%) who always and 53 (37.6%) who mostly found time
      to educate the patients about the various options available for renal failure
      treatment. Educational tools, such as reading materials and audiovisuals, were
      only available to 56 respondents (42.7%). There were 88 (63.3%) respondents who
      always discussed results of laboratory tests in detail with their dialysis
      patients, while 48 (34.5%) informed patients when any abnormality was discovered.
      There were 130 respondents (94.9%) who believed that their patients were
      satisfied with services of the physicians, 53 (39.0%) with the dietitian's, 57
      (42.5%) with the social worker's, and 131 (94.9%) with the nurses' services. Our
      survey suggests that that the current practices concerning education and
      rehabilitation of patients in the dialysis centers in the KSA may not be
      satisfactory. More studies are needed to explore these issues.

PMID- 17186687
TI  - Association of serum leptin with anemia in maintenance hemodialysis patients.
AB  - To evaluate the relationship between hyperleptinemia and anemia in hemodialysis
      patients, we investigated the reverse epidemiological role of leptin in 36
      patients (males: 21, diabetics: 11) under regular chronic hemodialysis. The
      patients had complete blood counts, iron profile, serum leptin, and adequacy of
      hemodialysis measured. We found a significant positive correlation of serum
      leptin with hemoglobin level and body mass index (BMI). A trend between serum
      leptin and total iron binding capacity was observed, however, no correlation was
      observed with serum ferritin. No differences in these correlations were observed
      in any subgroup related to gender or diabetes. Our data support previous findings
      showing that greater serum leptin levels are associated with greater hemoglobin
      levels.

PMID- 17186689
TI  - An accelerated method for the detection of extended-spectrum beta-lactamases in
      urinary isolates of Escherichia coli and Klebsiella pneumoniae.
AB  - We prospectively studied an accelerated phenotypic method by incorporating the
      double disk synergy test in the standard Kirby-Bauer disk diffusion
      susceptibility testing, to evaluate a protocol for the rapid detection of
      extended-spectrum beta-lactamases (ESBL) in urinary isolates of Escherichia coli
      (E. coli) and Klebsiella pneumoniae (K. pneumoniae). All ESBL-positive isolates
      were confirmed by the standard Clinical Laboratory Standards Institute (CLSI)
      confirmatory disk diffusion method. Between November 2004 and December 2005, a
      total of 6988 urine specimens were analyzed of which, 776 (11%) showed
      significant growth. They included E. coli in 577 cases (74%) and K. pneumoniae in
      199 (25.6%). Of these, 63 E. coli (8%) and 15 K. pneumoniae (7.5%) were positive
      for ESBL by the accelerated and CLSI methods. Compared to the standard CLSI
      method, the accelerated method reduced the ESBL detection time from two days to
      one day. We conclude that the accelerated ESBL detection technique used by us in
      this study is a reliable and rapid method for detecting ESBL in urinary isolates
      of E. coli and K. pneumoniae.

PMID- 17186690
TI  - The place of ultrasound in renal medicine.
AB  - Today, ultrasound is one of the most commonly used diagnostic tools, the reasons
      being that it is non-invasive, reliable, widely available, and affordable. In
      this paper, we review the place of ultrasound in the diagnosis and follow-up of
      patients with kidney diseases. We briefly discuss a wide range of kidney diseases
      for which ultrasound imaging is still performed as one of the initial steps of
      diagnosis. To achieve this, five following categories are addressed: congenital
      anomalies of the kidney; renal cystic diseases; renal infections; kidney stones;
      and kidney tumors. The sonographic findings of these diseases are discussed.

PMID- 17186691
TI  - Pre-emptive pediatric renal transplantation.

PMID- 17186692
TI  - Pyoderma gangrenosum in a renal transplant recipient: a case report.
AB  - Pyoderma gangrenosum (PG) is an ulcerative disease of the skin of unknown
      etiology. Its association with infection, autoimmune disease, inflammatory bowel
      disease, malignancy, and certain drugs suggests a hypersensitivity reaction. We
      herewith present a renal transplant recipient who developed PG. The patient
      presented with multiple necrotizing skin ulcers on both the upper and lower
      extremities associated with malaise, myalgia, arthralgia, weight loss and low
      grade fever. To our knowledge, the association between PG and renal transplant
      has not been reported previously.

PMID- 17186693
TI  - Bone marrow transplantation for leukocyte adhesion deficiency-I: case report.
AB  - Leukocyte adhesion deficiency type I (LAD-I) is a rare autosomal recessive
      immunodeficiency syndrome leading to recurrent bacterial and fungal infections.
      Bone marrow transplantation offers the only cure. In this report, we describe the
      course and outcome of bone marrow transplant in a 4 month-old female infant with
      LAD-I at King Hussein Medical Center, Jordan. A successful matched HLA- related
      allogeneic bone marrow transplantation was performed. Engraftment was
      demonstrated on the 12th day. The patient developed Grade III grafts versus host
      disease (GVHD), veno-occlusive disease of the liver, and late onset hemorrhagic
      cystitis. She recovered with appropriate immune reconstitution.

PMID- 17186694
TI  - Massive gastrointestinal bleeding and intestinal perforation in a renal
      transplant recipient: a case report.
AB  - Gastrointestinal (GI) hemorrhage is a problem, the management of which needs the
      right decision at the right time and close cooperation between physicians and
      surgeons. We herewith report a renal transplant recipient who developed severe GI
      bleed and intestinal perforations seven months after renal transplantation.
      Despite extensive investigations, the exact cause of the problem could not be
      identified.

PMID- 17186696
TI  - Renal angiomyxoma.

PMID- 17186695
TI  - Ectopia vasa deferentia inguinal hernia, vesicourteric reflux, imperforate anus,
      and recto-vesical fistula: a case report.
AB  - Urologic congenital anomalies are frequently associated with anorectal
      abnormalities. Vas deferens anomalies in the general population are estimated to
      be less than 0.05%. Many of the abnormalities can be explained by events in early
      fetal life. Urosepsis and epididymitis are the usual presenting signs and
      symptoms in such patients. We describe an infant who was discovered after birth
      to have an association of high imperforate anus with recto-vesical fistula, right
      inguinal hernia, left vesicoureteral reflux, and bilateral dilated vasa
      deferentia ectopically terminating in the posterior urethra, which caused
      recurrent epididymo-orchitis.

PMID- 17186697
TI  - Transplantation of a lump or cake kidney: a case report.

PMID- 17186698
TI  - Helicobacter pylori infection in dialysis patients undergoing kidney
      transplantation.

PMID- 17186699
TI  - Pediatric end-stage renal disease: single center analysis.
AB  - Data describing end stage renal disease in Jordan is very limited, due to the
      absence of internal center as well as national registry systems. In this
      retrospective analysis, we define the etiology, prevalence, incidence as well as
      other demographic features of pediatric end stage renal disease and renal
      replacement therapy at King Hussein Medical Center. All children who entered the
      chronic dialysis program in our center from January 2001 to December 2005 were
      included in the study. Children who were transplanted pre-emptively were also
      included. A total number of 42 patients were included. The mean age at time of
      dialysis initiation was 11.10+/-2.25 years; 19 (45.2%) were males. The prevalence
      of ESRD in Jordan children was calculated to be 14.5 patients per million.
      Hemodialysis (HD) was the primary modality of therapy in 40 (95.2%) patients. The
      most common cause of ESRD in our children was acquired glomerulopathy in 13 (31%)
      patients, followed by oxalosis in seven (16.7%), and neurogenic bladder in six
      (14.3 %). Thirteen patients were transplanted; the one and three year graft
      survival rates were 87.5% and 72.5%, respectively. We conclude that there are
      some peculiar features for pediatric ESRD in Jordan including the high incidence
      of oxalosis and neurogenic bladder. A national registry for children with ESRD
      should be established as this may have serious implications on the choice of
      renal replacement therapy.

PMID- 17186700
TI  - Why patients get upset by their doctors.

PMID- 17186702
TI  - Organ donation and transplantation in the Kingdom of Saudi Arabia 2005.

PMID- 17186701
TI  - Tumorlysis by dialysis.

PMID- 17186703
TI  - Systems theory of Smad signalling.
AB  - Transforming growth factor-beta (TGFbeta) signalling is an important regulator of
      cellular growth and differentiation. The principal intracellular mediators of
      TGFbeta signalling are the Smad proteins, which upon TGFbeta stimulation
      accumulate in the nucleus and regulate the transcription of target genes. To
      investigate the mechanisms of Smad nuclear accumulation, we developed a simple
      mathematical model of canonical Smad signalling. The model was built using both
      published data and our experimentally determined cellular Smad concentrations
      (isoforms 2, 3 and 4). We found in mink lung epithelial cells that Smad2 (8.5-12
      x 10(4) molecules cell(-1)) was present in similar amounts to Smad4 (9.3-12 x
      10(4) molecules cell(-1)), whereas both were in excess of Smad3 (1.1-2.0 x 10(4)
      molecules cell(-1)). Variation of the model parameters and statistical analysis
      showed that Smad nuclear accumulation is most sensitive to parameters affecting
      the rates of R-Smad phosphorylation and dephosphorylation and Smad complex
      formation/ dissociation in the nucleus. Deleting Smad4 from the model revealed
      that rate-limiting phospho-R-Smad dephosphorylation could be an important
      mechanism for Smad nuclear accumulation. Furthermore, we observed that binding
      factors constitutively localised to the nucleus do not efficiently mediate Smad
      nuclear accumulation, if dephosphorylation is rapid. We therefore conclude that
      an imbalance in the rates of R-Smad phosphorylation and dephosphorylation is
      likely an important mechanism of Smad nuclear accumulation during TGFbeta
      signalling.

PMID- 17186704
TI  - Direct Lyapunov exponent analysis enables parametric study of transient
      signalling governing cell behaviour.
AB  - Computational models aid in the quantitative understanding of cell signalling
      networks. One important goal is to ascertain how multiple network components work
      together to govern cellular responses, that is, to determine cell 'signal
      response' relationships. Several methods exist to study steady-state signals in
      the context of differential equation-based models. However, many biological
      networks influence cell behaviour through time-varying signals operating during a
      transient activated state that ultimately returns to a basal steady-state. A
      computational approach adapted from dynamical systems analysis to discern how
      diverse transient signals relate to alternative cell fates is described. Direct
      finite-time Lyapunov exponents (DLEs) are employed to identify phase-space
      domains of high sensitivity to initial conditions. These domains delineate
      regions exhibiting qualitatively different transient activities that would be
      indistinguishable using steady-state analysis but which correspond to different
      outcomes. These methods are applied to a physicochemical model of molecular
      interactions among caspase-3, caspase-8 and X-linked inhibitor of apoptosis-
      proteins whose transient activation determines cell death against survival fates.
      DLE analysis enabled identification of a separatrix that quantitatively
      characterises network behaviour by defining initial conditions leading to
      apoptotic cell death. It is anticipated that DLE analysis will facilitate
      theoretical investigation of phenotypic outcomes in larger models of signalling
      networks.

PMID- 17186705
TI  - Primary mouse hepatocytes for systems biology approaches: a standardized in vitro
      system for modelling of signal transduction pathways.
AB  - Complex cellular networks regulate regeneration, detoxification and
      differentiation of hepatocytes. By combining experimental data with mathematical
      modelling, systems biology holds great promises to elucidate the key regulatory
      mechanisms involved and predict targets for efficient intervention. For the
      generation of high-quality quantitative data suitable for mathematical modelling
      a standardised in vitro system is essential. Therefore the authors developed
      standard operating procedures for the preparation and cultivation of primary
      mouse hepatocytes. To reliably monitor the dynamic induction of signalling
      pathways, the authors established starvation conditions and evaluated the extent
      of starvation-associated stress by quantifying several metabolic functions of
      cultured primary hepatocytes, namely activities of glutathione-S-transferase,
      glutamine synthetase, CYP3A as well as secretion of lactate and urea into the
      culture medium. Establishment of constant metabolic activities after an initial
      decrease compared with freshly isolated hepatocytes showed that the cultured
      hepatocytes achieve a new equilibrium state that was not affected by our starving
      conditions. To verify the highly reproducible dynamic activation of signalling
      pathways in the in vitro system, the authors examined the JAK-STAT, SMAD, PI3
      kinase, MAP kinase, NF-kappaB and Wnt/beta-catenin signalling pathways. For the
      induction of gp130, JAK1 and STAT3 phosphorylation IL6 was used, whereas TGFbeta
      was applied to activate the phosphorylation of SMAD1, SMAD2 and SMAD3. Both
      Akt/PKB and ERK1/2 phosphorylation were stimulated by the addition of hepatocyte
      growth factor. The time-dependent induction of a pool of signalling competent
      beta-catenin was monitored in response to the inhibition of GSK3beta. To analyse
      whether phosphorylation is actually leading to transcriptional responses,
      luciferase reporter gene constructs driven by multiple copies of TGFbeta
      responsive motives were applied, demonstrating a dose-dependent increase in
      luciferase activity. Moreover, the induction of apoptosis by the TNF-like
      cytokine Fas ligand was studied in the in vitro system. Thus, the mouse
      hepatocyte in vitro system provides an important basis for the generation of high
      quality quantitative data under standardised cell culture conditions that is
      essential to elucidate critical hepatocellular functions by the systems biology
      approach.

PMID- 17186706
TI  - Elimination of the initial value parameters when identifying a system close to a
      Hopf bifurcation.
AB  - One of the biggest problems when performing system identification of biological
      systems is that it is seldom possible to measure more than a small fraction of
      the total number of variables. If that is the case, the initial state, from where
      the simulation should start, has to be estimated along with the kinetic
      parameters appearing in the rate expressions. This is often done by introducing
      extra parameters, describing the initial state, and one way to eliminate them is
      by starting in a steady state. We report a generalisation of this approach to all
      systems starting on the centre manifold, close to a Hopf bifurcation. There exist
      biochemical systems where such data have already been collected, for example, of
      glycolysis in yeast. The initial value parameters are solved for in an
      optimisation sub-problem, for each step in the estimation of the other
      parameters. For systems starting in stationary oscillations, the sub-problem is
      solved in a straight-forward manner, without integration of the differential
      equations, and without the problem of local minima. This is possible because of a
      combination of a centre manifold and normal form reduction, which reveals the
      special structure of the Hopf bifurcation. The advantage of the method is
      demonstrated on the Brusselator.

PMID- 17186707
TI  - Decreased internalisation of erbB1 mutants in lung cancer is linked with a
      mechanism conferring sensitivity to gefitinib.
AB  - A majority of gefitinib (IRESSA)-responsive tumours in non-small cell lung cancer
      have been found to carry mutations in ErbB1. Previously, it has been observed
      that internalisation-deficient ErbB1 receptors are strong drivers of oncogenesis.
      Using a computational model of ErbB1 trafficking and signalling, it is found that
      a deficiency in ErbB1 internalisation is sufficient to explain the observed
      signalling phenotype of these gefitinib-responsive ErbB1 mutants in lung cancer
      cell lines. Experimental tests confirm that gefitinib-sensitive cell lines with
      and without ErbB1 mutations exhibit markedly slower internalisation rates than
      gefitinib-insensitive cell lines. Moreover, the computational model demonstrates
      that reduced ErbB1 internalisation rates are mechanistically linked to
      upregulated AKT signalling. Experimentally it is confirmed that impaired
      internalisation of ErbB1 is associated with increased AKT activity, which can be
      blocked by gefitinib. On the basis of these experimental and computational
      results, it is surmised that gefitinib sensitivity is a marker of a reliance on
      AKT signalling for cell survival that may be brought about by impaired ErbB1
      internalisation.

PMID- 17186708
TI  - Health care and insurance issues for transgender persons.

PMID- 17186709
TI  - Family physicians and immunizations.

PMID- 17186711
TI  - Information from your family doctor. Parkinson's disease: what you should know.

PMID- 17186710
TI  - Parkinson's disease: diagnosis and treatment.
AB  - Parkinson's disease is a common neurodegenerative disorder that can cause
      significant disability and decreased quality of life. The cardinal physical signs
      of the disease are distal resting tremor, rigidity, bradykinesia, and asymmetric
      onset. Levodopa is the primary treatment for Parkinson's disease; however, its
      long-term use is limited by motor complications and drug-induced dyskinesia.
      Dopamine agonists are options for initial treatment and have been shown to delay
      the onset of motor complications. However, dopamine agonists are inferior to
      levodopa in controlling motor symptoms. After levodopa-related motor
      complications develop in advanced Parkinson's disease, it is beneficial to
      initiate adjuvant therapy with dopamine agonists, catechol O-methyltransferase
      inhibitors, or monoamine oxidase-B inhibitors. Deep brain stimulation of the
      subthalamic nucleus has been shown to ameliorate symptoms in patients with
      advanced disease. Depression, dementia, and psychosis are common psychiatric
      problems associated with Parkinson's disease. Psychosis is usually drug induced
      and can be managed initially by reducing antiparkinsonian medications. The
      judicious use of psychoactive agents may be necessary. Consultation with a
      subspecialist is often required.

PMID- 17186713
TI  - Vasectomy: an update.
AB  - Vasectomy remains an important option for contraception. Research findings have
      clarified many questions regarding patient selection, optimal technique,
      postsurgical follow-up, and risk of long-term complications. Men who receive
      vasectomies tend to be non-Hispanic whites, well educated, married or
      cohabitating, relatively affluent, and have private health insurance. The
      strongest predictor for wanting a vasectomy reversal is age younger than 30 years
      at the time of the procedure. Evidence supports the use of the no-scalpel
      technique to access the vasa, because it is associated with the fewest
      complications. The technique with the lowest failure rate is cauterization of the
      vasa with or without fascial interposition. The ligation techniques should be
      used cautiously, if at all, and only in combination with fascial interposition or
      cautery. A single postvasectomy semen sample at 12 weeks that shows rare,
      nonmotile sperm or azoospermia is acceptable to confirm sterility. No data show
      that vasectomy increases the risk of prostate or testicular cancer.

PMID- 17186714
TI  - Information from your family doctor. Vasectomy: what you should know.

PMID- 17186712
TI  - Newer agents for the management of overactive bladder.
AB  - The anticholinergics tolterodine and oxybutynin are well established in the
      management of overactive bladder. However, their activity at muscarinic receptors
      distant from the target site (i.e., bladder) produces anticholinergic side
      effects leading to poor tolerability. In 2004, trospium, solifenacin, and
      darifenacin were approved by the U.S. Food and Drug Administration for the
      treatment of overactive bladder. Trospium is water soluble and therefore is less
      likely to enter the central nervous system, and solifenacin and darifenacin are
      more selective for the bladder than older agents. Although these attributes could
      improve tolerability, clinical trials comparing relevant agents to validate this
      are lacking. Trials have shown that these newer agents decrease the frequency of
      incontinence episodes, the number of voids per day, and the number and severity
      of urgency episodes compared with placebo. These agents also have been shown to
      improve quality of life in women with overactive bladder and urinary
      incontinence. Head-to-head studies of the newer agents and immediate-release
      oxybutynin and tolterodine have suggested similar effectiveness across the class,
      although the newer agents are better tolerated. Trospium and darifenacin have not
      been compared with extended-release formulations of tolterodine or oxybutynin,
      which are better tolerated than the immediate-release versions. In one study,
      solifenacin produced a somewhat greater decrease in the number of incontinence
      episodes than extended-release tolterodine, with no difference in tolerability.
      In general, the newer agents appear to be at least as effective as their
      predecessors, although it is unclear whether they are better tolerated. Important
      pharmacokinetic differences among the agents (e.g., route of elimination) allow
      for selection of an appropriate agent based on individual factors such as cost
      and tolerability.

PMID- 17186715
TI  - Evaluation of children with reading difficulties.
AB  - Reading difficulties are common and are associated with poor long-term academic
      achievement. Evaluation of a child's developmental, educational, and family
      histories in conjunction with standardized screening tests (e.g., Ages and Stages
      Questionnaires, Parents' Evaluation of Developmental Status, Safety Word
      Inventory and Literacy Screener) can increase recognition of risk factors for
      reading difficulties. Validated, office-based, standardized screening tests and
      school-administered standardized achievement tests (e.g., California Achievement
      Tests, Iowa Tests of Basic Skills, Metropolitan Achievement Tests, Stanford
      Achievement Test) can be used to assess school-age children with reading
      difficulties. Reading difficulties in children often are caused by environmental
      and organic risk factors. However, many children have reading or learning
      disabilities and will have lifelong difficulties with reading despite adequate
      intervention. Children with substantial reading difficulties should receive a
      full educational assessment. There is good evidence that individualized
      instruction emphasizing increased phonologic awareness can have a favorable long
      term effect on academic achievement.

PMID- 17186716
TI  - Diagnosis of migraine headache.

PMID- 17186717
TI  - Chronic, draining perianal sinuses.

PMID- 17186718
TI  - Information from your family doctor. Exercise: how to get started.

PMID- 17186719
TI  - Information from your family doctor. Exercise: a healthy habit to start and keep.

PMID- 17186720
TI  - Information from your family doctor. Weight control: the power of healthy
      choices.

PMID- 17186721
TI  - [Study on brain response to acupuncture by functional magnetic resonance imaging-
      observation on 14 healthy subjects].
AB  - OBJECTIVE: To observe the signal changes of brain functional area during needling
      Sanyinjiao (ST36), Zusanli (SP6) and Yanglingquan (GB34), the three acupoints in
      three different meridians, in human by functional magnetic resonance imaging
      (fMRI), in order to preliminary explore the neural mechanism of acupuncture.
      METHODS: Needling was complemented with 30 s of maneuver applying followed by 30
      s of rest as a circle on an acupoint, and at the same time, fMRI was performed
      once 5 min and 12 s. Then the same program was repeated with the same mode on
      another acupoint, until ending the experiment. RESULTS: The commonly activated
      regions were postcentral gyrus and right inferior frontal gyrus when needling at
      ST36 and SP6, and the different activated areas included left inferior frontal
      gyrus, left insula, left inferior parietal lobule, left culmen, left middle
      temporal gyrus and left middle frontal gyrus, while no cortical signal enhanced
      region was found when needling at GB34. Signal weakened regions could be found
      when needling at all the three points, the commonly activated regions were
      bilateral parahippocampal, hippocampal, callosal gyrus, bilateral praecuneus and
      cerebellum. CONCLUSION: Brain response in special regions could be obtained by
      needling at different acupoints.

PMID- 17186722
TI  - [Effects of acupuncture at Weizhong (BL40) on brain function with PET/CT].
AB  - OBJECTIVE: To observe the effect of needling at Weizhong (BL 40) acupoint in
      inducing metabolic changes in brain with positron emission tomography and dynamic
      contrast (PET/CT) imaging for exploring the mechanism of central regulation of
      acupuncture. METHODS: PET/CT was performed before and during needling Weizhong
      acupoint of right leg by electro-acupuncture in 8 healthy volunteers, and also in
      other 8 subjects without any acupoint stimulation for control. Difference of
      brain functional images between the two groups before and during needling was
      analyzed by pairing t-test with statistical parametric mapping. RESULTS: The
      needling evoked mean activated cerebral functional regions were: left Broadmann
      area (BA) 10, 11, 22, 38, 39, 40, 44-46, right BA10, bilateral BA18, 19, and left
      cerebellar cortex, claustrum and insula (t > 3.36, P < 0.01, k >30 voxels); its
      mean inhibited brain functional regions were: bilateral BA24, left BA7, 8, 19,
      40, right BA 1, 3, 6, 20, 44, and left substantia nigra. CONCLUSION: There is a
      certain connection between Weizhong acupoint and the brain. Needling this
      acupoint could exert effects through activating or inhibiting brain function in
      specific regions and neurohumoral regulation. One of the central regulation
      mechanisms of acupuncture was functional activation in superior, middle, and
      inferior frontal gyrus, insula and cerebellum and functional inhibition in
      callosal gyrus, lobi parietalis and substantia nigra. This study further
      demonstrated PET/CT is useful in revealing TCM meridian theory and could provide
      objective proof of central regulation for acupuncture treatment.

PMID- 17186723
TI  - [Changes in T-cell receptor repertoire in aplastic anemia and effects of Shengxue
      Mixture].
AB  - OBJECTIVE: To explore the immune pathogenesis of aplastic anemia (AA) and the
      therapeutic effects of Shengxue Mixture (SM) through the gene expressions of
      subfamilies of T-cell receptor variable region beta (TCR Vbeta) using immunologic
      and molecular biologic technology. METHODS: Gene expressions of TCR Vbeta sub
      families in peripheral blood mononuclear cells from 20 AA patients were detected
      before and after treatment with SM using RT-PCR and gene scanning method.
      RESULTS: TCR Vbeta gene repertoire of the 24 subfamily genes deviated in AA
      patients, and the oligoclonal gene expressions increased obviously compared with
      those in healthy people (P < 0.01), including Vbeta2, 5, 6, 15, 16, 22, and 23
      were found in 30%-50% AA patients, and Vbeta8, 21 were in more than 50% patients.
      These oligoclonal genes reduced significantly after treatment with SM compared
      with those before treatment (P < 0.05). CONCLUSION: Multiple TCR Vbeta
      subfamilies of clonal proliferation participate in the pathogenesis of AA. SM can
      rectify the deviation of TCR Vbeta gene repertoire, reduce the abnormal clonal
      proliferation of T cells, thus to alleviate the immune injury to hematopoietic
      tissue, and thus to benefit the recovery of hematopoiesis of bone marrow.

PMID- 17186724
TI  - [Clinical and pathological study on effects of Qianggan Capsule combined
      lamivudine on hepatic fibrosis in patients with chronic hepatitis B].
AB  - OBJECTIVE: To study the therapeutic effects of Qianggan Capsule (QC) combined
      Lamivudine on hepatic fibrosis in patients with chronic hepatitis B. METHODS:
      Eighty-five patients were randomly divided into two groups, group A (40 cases)
      were treated with QC and Lamivudine and group B (45 cases) were treated with QC
      alone both for 6 months. Hepatic fibrosis related indexes and pathologic
      examination of liver biopsy were performed within 3 months before treatment and
      in 1 month after treatment. RESULTS: Serum levels of hyaluronic acid, collagen N
      and laminin decreased markedly after treatment in both groups (P < 0.05). Hepatic
      histopathological examination showed that the total effective rate of impovement
      in activity of inflammation-necrosis and fibrosis was 80.0% and 70.0% in group A,
      57.8% and 75.6% in group B, respectively, the combined treatment showed a better
      effect in improving the activity of inflammation-necrosis than QC alone (P <
      0.05), but with no significant difference to the latter in improving fibrosis.
      CONCLUSION: QC combined Lamivudine could markedly reduce the activity of hepatic
      inflammation-necrosis, QC alone could also improve hepatic fibrosis.

PMID- 17186725
TI  - [Clinical observation on chronic severe hepatitis B treated by principles of
      cooling-blood and detoxicating combined with clearing-heat and resolving-damp or
      combined with strengthening-Pi and warming-yang].
AB  - OBJECTIVE: To observe the therapeutic efficacy on chronic severe hepatitis B
      (CSH) patients of Yanghuang and Yinhuang syndrome type by principles of cooling
      blood and detoxicating combined with clearing-heat and resolving dampness (PA) or
      with strengthening-Pi and warming-yang (PB), respectively. METHODS: Forty-three
      patients with CSH were randomly divided into two groups, group A (22 cases)
      treated with PA and group B (21 cases) with PB. The therapeutic efficacy, laying
      stress on the effect in eliminating jaundice, was observed. RESULTS: The efficacy
      in group B was effective in 19 cases (90.5%), and ineffective in 2 (9.5%), while
      in group A, effective in 16 (72.7%) and ineffective in 6 (27.3%). Levels of TBIL
      and ALT were significantly lower in both groups (P < 0.05 or P < 0.01), and the
      descending extent was greater, the thrombinogen activity was higher in group B
      than that in group A after treatment (P < 0.05), no significant difference in ALT
      was found between the two groups. CONCLUSION: The efficacy of PB is better than
      that of PA on CSH with Yanghuang and Yinghuang syndrome.

PMID- 17186726
TI  - [Effects of drug cupping therapy on immune function in chronic asthmatic
      bronchitis patients during protracted period].
AB  - To observe the clinical effect of drug cupping therapy (DCT, cupping therapy with
      pingchuan ointment made by the authors themselves in the cups) on chronic
      asthmatic bronchitis (CAB) during the protracted period, and explore its effect
      on immune function. METHODS: Seventy-seven patients were randomly divided into
      two groups:the treated group (n=40) treated by orally taken Liuwei Dihuang Pill
      (LDP) and DCT and the control group (n=37) with LDP and common cupping therapy
      without drug in cups. The changes of T-lymphocyte subset, levels of interferon
      gamma (IFN-gamma), interleukin (IL), immunoglobulin (Ig), complement 3 and 4 (C3
      and C4) were detected before and after treatment. RESULTS: The total effective
      rate was higher in the treated group than that in the control group (90.0% vs.
      59.5%, P < 0.01). The levels of CD4+, CD4+ /CD8+, IL-2, IFN-gamma, C3, C4, IgA,
      IgG and IgM increased, while the levels of IgE, IL-4, IL-10 and CD8+ decreased
      after treatment in both groups (P < 0.05 or P < 0.01), the improvements were
      better in the treated group than that in the control group (P < 0.05).
      CONCLUSION: DCT shows better curative effects than that of common cupping therapy
      without drug, it could improve the cellular and humoral immunity in CAB patients.

PMID- 17186727
TI  - [Comparative analysis via data mining on the clinical features of Western
      medicine and Chinese medicine in diagnosing rheumatoid arthritis].
AB  - OBJECTIVE: To compare the clinical characteristics of traditional Chinese
      medicine (TCM) and Western medicine (WM) in diagnosing rheumatoid arthritis (RA).
      METHODS: A total of 85 clinical RA related messages were enacted and classified
      into 5 sets as pathological locations, quantitative diagnosis, symptomatic
      descriptions, general status and environment factors. The respective frequency of
      their presence in the TCM or WM data sets for RA diagnosis collected from MEDLINE
      and China National Knowledge Infrastructure (CNKI) were analyzed statistically by
      Chi-square test, and the relationship of some TCM diagnostic factors/conditions
      with the RA related biological factors was analyzed by co-occurrence-based
      literature approach of mining. RESULTS: There was significant difference between
      the diagnostic pattern of WM and TCM (P < 0.01). Compared with that of WM, TCM
      diagnosis on RA paid more attention to environmental factors and symptomatic
      descriptions, which showed definite association with the cytokines and neuro
      endocrine factors in RA. CONCLUSION: Examination of environmental factors and
      symptomatic descriptions for RA diagnosis is one of the important characteristics
      of TCM treatment in accordance to syndrome differentiation, it has its potential
      biologic basis. A novel approach is proposed for exploring the characteristics of
      TCM in diagnosis and observation.

PMID- 17186728
TI  - [Research on relationship of syndrome type and parameters of hemorheology and
      platelet activation in patients with acute gout arthritis of dampness-heat
      blockage type and stasis-heat accumulate type].
AB  - OBJECTIVE: To study the relationship between syndrome type and the parameters of
      hemorrheology and platelet activation in patients with acute gout arthritis of
      dampness-heat blockage (DHB) type and stasis-heat accumulation (SHA) type.
      METHODS: Forty patients with acute gouty arthritis were divided into 2 groups
      according to TCM syndrome differentiation, the DHB group (n=24) and the SHA group
      (n=16), and 20 healthy people were taken as the control group. Hemorrheological
      parameters, platelet activating factor (PAC-1) and P-selection (CD62p) in them
      were detected. RESULTS: Plasma viscosity, outcome of erythrocyte sedimentation
      and K value of its equation, levels of PAC-1 and CD62p were higher, erythrocyte
      electrophoresis index was significantly lower in gout patients of both types than
      those in the control group (all P < 0.01), and the levels of PAC-1 and CD62p in
      the SHA group were higher than those in the DHB group (P < 0.05). CONCLUSION: DHB
      type and SHA syndrome type of acute gout arthritis are correlated with parameters
      of hemorrheology and platelet activation, and the different levels of these
      pameters showed in the two types, may be the internal factors for their genesis.

PMID- 17186729
TI  - [Clinical monitoring of tissue oxygen pressure on acupoint Zusanli (ST36) of
      patients in critical condition].
AB  - OBJECTIVE: To observe the local tissue oxygenation in acupoint Zusanli (ST36) of
      patients in critical condition, and to assess the value of applying tissue oxygen
      measurement via acupoint in clinical practice. METHODS: Thirty-six patients with
      severe illness undergoing invasive positive pressure ventilation (IPPV) were
      divided into the infected group (n=13) and the non-infected group (n=23). Tissue
      oxygen pressure (PtO2) in the right acupoint Zusanli was measured with tissue
      oxygen tension detector when the concentration of inspired oxygen (FiO2) was 40%
      and 100% respectively, meanwhile, the arterial blood oxygen pressure (PaO2) was
      also determined to calculate PtO2 index (the ratio of PtO2/PaO2). RESULTS: There
      was a positive correlation between PtO2 and PaO2 (P < 0.05); PaO2 in the infected
      group was lower, and PtO2 index and PtO2 were higher significantly, as compared
      with those in the non-infected group (all P < 0.05). As FiO2 adjusted from 40% to
      100%, the increment of PtO2 in the infected group was significantly higher than
      that in the non-infected group (P < 0.05). CONCLUSION: For the severely infected
      patients with obstacle of systemic oxygen delivery, the local tissue oxygen
      demand of acupoints increases significantly, and the tissue oxygen delivery
      dependence is enhanced, in this time, the tissue might fulfill the oxygen demand
      itself through elevating PtO2 index. It is of great significance to monitor
      tissue oxygen pressure in acupoint to determine the state of local tissue
      oxygenation in critically illed patients.

PMID- 17186730
TI  - [Rules of protein expression of proto-oncogene (c-Fos/c-Jun) in different brain
      areas and nucleus of psychological stressed mice and the regulatory effect of
      modified Xiaoyao Pill].
AB  - OBJECTIVE: To study the rules of protein expression of proto-oncogene (c-Fos/c
      Jun) in different brain areas and nucleus of psychological stressed mice and the
      regulatory effect of modified Xiaoyao Pill (SXP). METHODS: The mouse
      psychological stress model was established by electrical stimulation; SXP was
      administrated at the dose of 2 mg/g; the protein expression of c-Fos and c-Jun in
      different brain areas and nucleus, including hippocampus (CA1-4), central
      amygdaloid nucleus (CAN), paraventricular nucleus (PVN) and supraoptic nucleus
      (SON), were detected by immunohistochemical method. RESULTS: The protein
      expressions of c-Fos and c-Jun in all the tested brain areas of model mice 3 h
      after being stressed for 1, 3 or 5 times, were significantly higher than those of
      the normal mice (P < 0.01); After being stressed for one time, the expression at
      1 h after stimulation was lower than that at 3 h after stimulation (P < 0.05),
      the expression in mice treated with SXP was lower than that in the untreated
      group, 3 h after three or five times of stress (P < 0.05 or P < 0.01).
      CONCLUSION: The protein expression of c-Fos and c-Jun began to rise 1 h after
      psychological stress and reached the peak at the 3rd h. That of c-Fos dropped to
      the normal level approximately after 6 h, but the dropping did not happen in
      expression of c-Jun, it remained on the high level unweakened after repeated
      stimulation; SXP can remarkably down-regulate the proto-oncogene (c-Fos and c
      Jun) expressions after psychological stress in mice.

PMID- 17186731
TI  - [Experimental study on osteoking in promoting gene expression of core binding
      factor alpha 1 in necrotic femoral head of rabbits].
AB  - OBJECTIVE: To study the effects of Osteoking in promoting gene expression of core
      binding factor alpha 1 (cbfalpha 1) in necrotic femoral head of rabbits. METHODS:
      Rabbit model of femoral head necrosis (FHN) was induced by intravenous injection
      of lipopolysaccharide (LPS) 10 microg/kg body weight twice with an interval of 24
      h and intramuscular injection with methyl prednisone (MPS) 20 mg/kg body weight 3
      times. The dynamic changes of cbfalpha 1 gene expression in the femoral head were
      observed with immunohistochemistry and real-time quantitative PCR. RESULTS: The
      protein expression of cbfa 1 gene was negative in both model and treatment groups
      at the 4th week, it turned to weakly positive in the treatment group at the 8th
      and 12th week but still negative in the model group. The mRNA expression of
      cbfalpha 1 in the treatment group was 2.87 times that in the model group at the
      12th week. There was no significant difference in cbfalpha 1 expression between
      the normal rabbits with or without Osteoking treatment. CONCLUSION: Osteoking
      could promote the endogenous cbfalpha 1 expression in the FHN, the effect is
      better along with the prolonging of the time applied. But it showed no affection
      on cbfalpha 1 expression in the normal femoral head of rabbits.

PMID- 17186732
TI  - [Inhibitory effects of Salvia miltiorrhiza injection coordinated with
      dexamethasone on interleukin-13 and eotaxin expression in lung of asthmatic
      rats].
AB  - OBJECTIVE: To investigate the molecular mechanism of inhibitory effect of Salvia
      miltiorrhiza Injection (SMI) coordinated with dexamethasone (DXM) on allergic
      airway inflammation in asthmatic rats. METHODS: Forty SD rats were randomly
      divided into 5 groups equally: the normal group, the asthma model group, the DXM
      group, the SMI group and the DXM + SMI group, they were treated with
      correspondant herbal medicines. Pathologic changes of lung tissue were obseved
      with HE stain, count of WBC and eosinophil (Eos) in bronchoalveolar lavage fluid
      (BALF) were estimated and the expressions of interleukin-13 (IL-13) and Eotaxin
      in lung tissue were measured by RT-PCR and SP method of immunohistochemistry
      assay. RESULTS: There was moderate inflammation in lung tissue in the SMI group,
      and mild inflammation in the DXM + SMI and the DXM group, which was similar to
      that in the normal group. Compared with the asthma model group, Eos and WBC count
      in BALF and the expression of IL-13 and Eotaxin in the lung tissue were
      significantly lower in the three treated groups (P < 0.05), particularly in the
      DXM + SMI group, showing a significant difference as compared with the other two
      groups (P < 0.05 or P < 0.01). Additionally, IL-13 expression was positively
      correlated with Eotaxin expression (r = 0.92, P < 0.01). CONCLUSION: SMI could
      inhibit the expression of IL-13 and Eotaxin in the lung of asthmatic rats,
      showing inhibitory effects synergistic with DXM on airway inflammation.

PMID- 17186733
TI  - [Anti-apoptosis effect of astragaloside on adriamycin induced rat's
      cardiotoxicity].
AB  - OBJECTIVE: To study the possible mechanism of anti-myocardial cell apoptosis of
      astragaloside induced by adriamycin (ADR). METHODS: Fifty SD rats were randomized
      into five groups: the normal control group,the model group, the astragaloside low
      dose (A-L) group, the astragaloside medium dose (A-M) group and the astragaloside
      high dose (A-H) group, 10 in each group. The normal control group was given
      normal saline by intraperitoneal injection, while the other four groups were
      given ADR by intraperitoneal injection once every other day for six times with
      the total dosage of 15 mg/kg. At the same time, different dosage of astragaloside
      was administrated by gavage to the three treated groups, and sodium
      carboxymethycellulose (SCMC) was given to the normal control and the model group.
      Myocardial cell apoptosis was examined by in situ end-labeled DNA (TUNEL),
      protein and mRNA expressions of bax, bcl-2 were detected respectively with
      immunohistochemistry assay and RT-PCR. RESULTS: Compared with those in the normal
      control, apoptosis index was significantly higher, the protein and mRNA
      expressions of bcl-2 were lower and those of bax were higher, in the model group,
      resulted in lower ratio of bcl-2/bax (P < 0.05 or P < 0.01). However, in the A-H
      group, apoptosis index decreased significantly, the expressions of bcl-2 were
      higher, those of bax were lower, and ratio of the bcl-2/bax increased (all P <
      0.05). CONCLUSION: High dose of astragaloside could suppress the myocardial cell
      apoptosis induced by ADR with the possible mechanism related to regulating the
      expressions of bcl-2 and bax.

PMID- 17186734
TI  - [Effects of emodin on proliferation cycle and apoptotic gene of human lung
      adenocarcinoma cell line Anip 973].
AB  - OBJECTIVE: To study the suppressive role of emodin on the growth and its effect
      on the proliferation cycle and apoptotic gene of human lung adenocarcinoma cell
      line Anip 973. METHODS: The survival rate and the inhibitory rate of Anip 973
      cell in vitro were detected by MTT colorimetric assay and cell growth curve assay
      at different time points under different concentration of emodin; the cell
      proliferation cycle and the apoptotic rate were examined with flow cytometry
      analysis, and Caspase-3 protein expression was measured by immunoblotting assay.
      RESULTS: Emodin inhibited the proliferation of Anip 973 cell at G0/G1 phase,
      decreased the cell ratio at S phase and activated the Caspase-3 protein. It
      suppressed the growth of tumor cells and raised the apoptotic rate in a
      concentration and time depending manner in a certain extent. CONCLUSION: Emodin
      could suppress the proliferation of Anip 973 cell, and its mechanism of
      anticancer effect may be through activating Caspase-3, to induce apoptosis and
      block cell cycle.

PMID- 17186735
TI  - [Effect of Bufei Qingyu Granule in mollifying skin of mouse scleroderma model].
AB  - OBJECTIVE: To investigate the effect and mechanism of Bufei Qingyu Granule (BQG)
      in mollifying the skin of scleroderma model mice. METHODS: Scleroderma model
      induced with bleomycin in BALB/C mice 8-weeks old were administered with
      different dose of BQG for 26 days. The pathological changes of the mice skin were
      observed. RESULTS: Treatment with low, medium and high dose of BQG showed a
      tendency to ameliorate the thickened dermis in scleroderma mice but without
      statistical significance. Medium and high dose of BQG reduced the perivasculitis
      of dermis and alleviated the reduction or deletion of accessory structure, such
      as hair follicle and sweat gland. And the spleen index was lower markedly in mice
      treated with BQG of any dose than that in the untreated model mice (P < 0.05).
      CONCLUSION: BQG could ameliorate the sclerosed skin in model mice and prevent the
      occurrence of splenomegaly.

PMID- 17186736
TI  - [Clinical observation on Qingling Dingxuan Decoction in treating vertigo cause by
      insufficient blood-supply of ventebrobasilar artery].
AB  - OBJECTIVE: To observe the therapeutic effect of Qingling Dingxuan Decoction (QDD)
      on vertigo caused by insufficient blood-supply of ventebrobasilar artery (IBVA).
      METHODS: Thirty-nine patients were divided into the flunarizine group (n=19) and
      the QDD group (n=20) treated with respective medicine on the base of routine
      treatment with Chinese and Western medicine. The clinical efficacy and recurrent
      rate were observed and compared. RESULTS: Compared with those in the flunarizine
      group, clinical curative effect was better, recurrent rate lower, symptom score
      higher, hemorheological parameters and transcranial doppler indexes were improved
      more significant in the QDD group (P < 0.01 or P < 0.05). CONCLUSION: QDD had
      obvious therapeutic effect on IBVA. Improvement of microcirculation and reduction
      of blood viscosity may be one of the therapeutical mechanisms.

PMID- 17186737
TI  - [Clinical observation on Qidi Yiqi Yangyin Huoxue Recipe in treating diabetic
      nephropathy at stage III and IV].
AB  - OBJECTIVE: To observe the clinical effect of Qidi Yiqi Yangyin Huoxue Recipe
      (QYYHR) on diabetic nephropathy (DN) at stage III and IV. METHODS: One hundred
      type 2 DN patients of qi-yin deficiency with blood-stasis syndrome were randomly
      divided into two groups, all were treated with basal hypoglycemic treatment but
      with QYYHR given to the treatment group additionally for 3 months. The symptoms
      were observed, blood glucose, urinary albumin excretion rate (UAER), blood urea
      nitrogen (BUN), creatinine (Cr) and hemorheological parameters were detected
      before and after treatment. RESULTS: The total effective rate was higher in the
      treatment group than that in the control group (89.6% vs. 68.1%, P < 0.01), and
      the improvement of UAER, BUN, Cr and hemorheological parameters was also
      significantly better in the former than in the latter (P < 0.05). CONCLUSION:
      QYYHR has favorable effects on type 2 DN of qi-yin deficiency with blood-stasis
      syndrome.

PMID- 17186738
TI  - [Effect of medicated bath plus acupoint massage on limbs in treating 42 patients
      with diabetic peripheral neuropathy].
AB  - OBJECTIVE: To observe the effect of medicated bath plus acupoint massage on limbs
      (B-M treatment) in treating diabetic peripheral neuropathy (DPN). METHODS: Eighty
      two patients were divided into two groups, the control group (n=40) and the
      treated group (n=42), they were treated by conventional treatment but with B-M
      treatment applied to the latter additionally, the course to both groups was 12
      weeks. The curative effects obtained were compared after treatment. RESULTS: The
      total effective rate was higher in the treated group than that in the control
      group (81.0% vs. 52.5%, P < 0.05); the nerval transmission speed was improved
      significantly (P < 0.05) after treatment in both group, but that in the treated
      group was better than in the control group (P < 0.05). CONCLUSION: B-M treatment
      on limbs has better effect than Western medicine along in promoting DPN
      restoration.

PMID- 17186739
TI  - [Strategy for treatment of acute myocardial infarction after coronary
      revascularization with integrative medicine].
AB  - Since 1980s, the treatment of acute myocardial infarction (AMI) has entered the
      era of revascularization of infarction-related artery. There is still shortness
      of ideal strategy in modern medicine for comprehensive intervention aiming at the
      complex pathological links such as myocardial no-reflow, slow-reflow and
      reperfusion injury after revascularization. Therefore, combining traditional
      Chinese medicine with modern medicine, selecting effective drugs or
      prescriptions, and exploring their effective ingredients and portions of them as
      well as the mechanisms of the combinations in promoting myocardial capillary
      angiogenesis and cardiac muscle cell differentiation, and regulating the
      repairing process of inflammatory reaction will provide new intervening target
      directions and comprehensive intervening patterns for the prevention and
      treatment of AMI.

PMID- 17186740
TI  - [Discussion on correlation between intrahepatic inflammatory pathogenesis and the
      TCM theory of liver collateral injury by toxins in patients of type 2 diabetes
      mellitus with insulin resistance].
AB  - Correlation between the intrahepatic inflammatory pathogenesis and the TCM theory
      of liver collateral injury by toxins in patients of type 2 diabetes mellitus
      (T2DM) with insulin resistance (IR) was investigated, to elucidate that removing
      toxins, dredging collateral and modulating Gan could be one of the effective
      approaches for inhibiting intrahepatic inflammation mechanism of T2DM with IR.

PMID- 17186741
TI  - [Comparison of the English titles of articles in Chinese and foreign academic
      journals: influences of difference between China and the foreign in thinking and
      psychology].
AB  - By analyzing the East-West difference in psychology and thinking patterns, the
      author compared the frequency of conventional words applied and the usage of
      subtitle, as well as the selection of sentence structure in title of articles,
      and thus advocated that the differences of attention psychology and thinking
      patterns, linear in the West and spiral in China, were the primary causes for
      different expressions of articles' title.

PMID- 17186742
TI  - [Research and prospect on reducing the toxicity and enhancing the efficacy of
      Tipterygium wilfordii by combined use of Chinese medicine].
AB  - Researches in recent close to dozen years concerning Tripterygium wilfordii (TW)
      toxicity-reducing and efficacy-enhancing by combined use of Chinese medicine in
      treating intractable diseases such as rheumatoid arthritis, nephropathy,
      psoriasis etc. were summarized in this paper. Furthermore, the therapeutic
      mechanisms and adverse reaction of TW were elaborated and how to arrange properly
      the TCM hebal drugs used in combination was analyzed.

PMID- 17186743
TI  - [Guideline for the diagnosis and treatment of liver fibrosis with integrative
      medicine].

PMID- 17186744
TI  - Enter the matrix: how to analyze the structure of behavior.
AB  - Several methods are available for analyzing different aspects of behavioral
      transition matrices, but a comprehensive framework for their use is lacking. We
      analyzed parasitoid foraging behavior in environments with different plant
      species compositions. The resulting complex data sets were analyzed using the
      following stepwise procedure. We detected abrupt changes in the event log files
      of parasitoids, using a maximum likelihood method. This served as a criterion for
      splitting the event log files into two parts. For both parts, Mantel's test was
      used to detect differences between first-order transition matrices, whereas an
      iterative proportional fitting method was used to find behavioral flows that
      deviated from random transitions. In addition, hidden repetitive sequences were
      detected in the transition matrices on the basis of their relative timing, using
      Theme. We discuss the results for the example from a biological context and the
      comprehensive use of the different methods. We stress the importance of such a
      combined stepwise analysis for detecting differences in some parts of event log
      files.

PMID- 17186745
TI  - A new methodological approach to nonverbal behavior analysis in cultural
      perspective.
AB  - The measurement of human behavior is a complex task, both for psychologists and
      human sciences researchers and with respect to technology, since advanced and
      sophisticated instruments may have to be implemented to manage the plurality of
      variables involved. In this article, an observational study is presented in which
      a quantitative procedure, the external variables method (Duncan & Fiske, 1977),
      was integrated with a structural analysis (Magnusson, 1993, 2000) in order to
      detect the hidden organization of nonverbal behavior in Italian and Icelandic
      interactions. To this aim, Theme software was introduced and employed. The
      results showed that both the frequency and the typology of gestures deeply change
      as a function of culture. Moreover, a high number of patterns was detected in
      both Italian and Icelandic interactions: They appeared to be complex sequences in
      which a huge number of events were constantly happening and recurring. In this
      domain, Theme software provides a methodological progression from the
      quantitative to the structural approach.

PMID- 17186746
TI  - Hidden patterns of play interaction in soccer using SOF-CODER.
AB  - Traditional methods for quantifying sport performances are limited in their
      capacity to describe the complex interactions of events that occur within a
      performance over time. The following article outlines a new approach to the study
      of actions between players in team sports--mainly, soccer. Since the
      observational design is nomothetic, point, and multidimensional, an observational
      and data-collecting instrument has been developed. The instrument is mixed and
      combines a field format with a category system for game events, as well as an ad
      hoc instrument that considers the game actions of one or both teams, each
      recorded according to the same criteria. The article also outlines a new approach
      to the analysis of time-based event records--in this case, sports performance-
      known as T-pattern detection. The relevant elements of the T-pattern detection
      process are explained, and exemplar data from analyses of soccer matches are
      presented to highlight the potential of this form of data analysis. The results
      suggest that it is possible to identify new kinds of profiles for both
      individuals and teams on the basis of observational criteria and a further
      analysis of temporal behavioral patterns detected within the performances.

PMID- 17186747
TI  - Developing a coding scheme for detecting usability and fun problems in computer
      games for young children.
AB  - This article describes the development and assessment of a coding scheme for
      finding both usability and fun problems through observations of young children
      playing computer games during user tests. The proposed coding scheme is based on
      an existing list of breakdown indication types of the detailed video analysis
      method (DEVAN). This method was developed to detect usability problems in task
      based products for adults. However, the new coding scheme for children's computer
      games takes into account that in games, fun, in addition to usability, is an
      important factor and that children behave differently from adults. Therefore, the
      proposed coding scheme uses 8 of the 14 original breakdown indications and has 7
      new indications. The article first discusses the development of the new coding
      scheme. Subsequently, the article describes the reliability assessment of the
      coding scheme. The any-two agreement measure of 38.5% shows that thresholds for
      when certain user behavior is worth coding will be different for different
      evaluators. However, the any-two agreement of .92 for a fixed list of observation
      points shows that the distinction between the available codes is clear to most
      evaluators. Finally, a pilot study shows that training can increase any-two
      agreement considerably by decreasing the number of unique observations, in
      comparison with the number of agreed upon observations.

PMID- 17186748
TI  - Quantifying social asymmetric structures.
AB  - Many social phenomena involve a set of dyadic relations among agents whose
      actions may be dependent. Although individualistic approaches have frequently
      been applied to analyze social processes, these are not generally concerned with
      dyadic relations, nor do they deal with dependency. This article describes a
      mathematical procedure for analyzing dyadic interactions in a social system. The
      proposed method consists mainly of decomposing asymmetric data into their
      symmetric and skew-symmetric parts. A quantification of skew symmetry for a
      social system can be obtained by dividing the norm of the skew-symmetric matrix
      by the norm of the asymmetric matrix. This calculation makes available to
      researchers a quantity related to the amount of dyadic reciprocity. With regard
      to agents, the procedure enables researchers to identify those whose behavior is
      asymmetric with respect to all agents. It is also possible to derive symmetric
      measurements among agents and to use multivariate statistical techniques.

PMID- 17186749
TI  - Recurrence plot analyses suggest a novel reference system involved in newborn
      spontaneous movements.
AB  - The movements of newborns have been thoroughly studied in terms of reflexes,
      muscle synergies, leg coordination, and target-directed arm/hand movements. Since
      these approaches have concentrated mainly on separate accomplishments, there has
      remained a clear need for more integrated investigations. Here, we report an
      inquiry in which we explicitly concentrated on taking such a perspective and,
      additionally, were guided by the methodological concept of home base behavior,
      which Ilan Golani developed for studies of exploratory behavior in animals.
      Methods from nonlinear dynamics, such as symbolic dynamics and recurrence plot
      analyses of kinematic data received from audiovisual newborn recordings, yielded
      new insights into the spatial and temporal organization of limb movements. In the
      framework of home base behavior, our approach uncovered a novel reference system
      of spontaneous newborn movements.

PMID- 17186750
TI  - Development and use of behavior and social interaction software installed on Palm
      handheld for observation of a child's social interactions with the environment.
AB  - In settings in developing countries, children often socialize with multiple
      socializing agents (peers, siblings, neighbors) apart from their parents, and
      thus, a measurement of a child's social interactions should be expanded beyond
      parental interactions. Since the environment plays a role in shaping a child's
      development, the measurement of child-socializing agents' interactions is
      important. We developed and used a computerized observational software Behavior
      and Social Interaction Software (BASIS) with a preloaded coding scheme installed
      on a handheld Palm device to record complex observations of interactions between
      children and socializing agents. Using BASIS, social interaction assessments were
      conducted on 573 preschool children for 1 h in their natural settings. Multiple
      screens with a set of choices in each screen were designed that included the
      child's location, broad activity, state, and interactions with child-socializing
      agents. Data were downloaded onto a computer and systematically analyzed. BASIS,
      installed on Palm OS (M-125), enabled the recording of the complex interactions
      of child-socializing agents that could not be recorded with manual forms. Thus,
      this tool provides an innovative and relatively accurate method for the
      systematic recording of social interactions in an unrestricted environment.

PMID- 17186751
TI  - Video-understanding framework for automatic behavior recognition.
AB  - We propose an activity-monitoring framework based on a platform called VSIP,
      enabling behavior recognition in different environments. To allow end-users to
      actively participate in the development of a new application, VSIP separates
      algorithms from a priori knowledge. To describe how VSIP works, we present a full
      description of a system developed with this platform for recognizing behaviors,
      involving either isolated individuals, groups of people, or crowds, in the
      context of visual monitoring of metro scenes, using multiple cameras. In this
      work, we also illustrate the capability of the framework to easily combine and
      tune various recognition methods dedicated to the visual analysis of specific
      situations (e.g., mono-/multiactors' activities, numerical/symbolic actions, or
      temporal scenarios). We also present other applications, using this framework, in
      the context of behavior recognition. VSIP has shown a good performance on human
      behavior recognition for different problems and configurations, being suitable to
      fulfill a large variety of requirements.

PMID- 17186752
TI  - Application testing of a new three-dimensional acceleration measuring system with
      wireless data transfer (WAS) for behavior analysis.
AB  - A wireless acceleration measurement system was applied to free-moving cows and
      horses. Sensors were available as a collar and a flat box for measuring leg or
      trunk movements. Results were transmitted simultaneously by radio or stored in an
      8-MB internal memory. As analytical procedures, frequency distributions with
      standard deviations, spectral analyses, and fractal analyses were applied.
      Bymeans of the collar sensor, basic behavior patterns (standing, grazing,
      walking, ruminating, drinking, and hay uptake) could be identified in cows.
      Lameness could be detected in cows and horses by means of the leg sensor. The
      portion of basic and harmonic spectral components was reduced; the fractal
      dimension was reduced. The system can be used for the detection and analysis of
      even small movements of free-moving humans or animals over several hours. It is
      convenient for the analysis of basic behaviors, emotional reactions, or events
      causing flight or fright or for comparing different housing elements, such as
      floors or fences.

PMID- 17186754
TI  - Objective measurement of upper limb activity and mobility during everyday
      behavior using ambulatory accelerometry: the upper limb activity monitor.
AB  - Ambulatory accelerometry is a technique that allows objective measurement of
      aspects of everyday human behavior. The aim of our research has been to develop,
      validate, and apply this technique, which recently resulted in an upper limb
      activity monitor (ULAM). The ULAM consists of body-mounted acceleration sensors
      connected to a waist-worn data recorder and allows valid and objective assessment
      of activity of both upper limbs during performance of also automatically detected
      mobility-related activities: lying, sitting, standing, walking, cycling, and
      general movement. The ULAM can be used to determine (limitations of) upper limb
      activity and mobility in freely moving subjects with upper limb disorders. This
      article provides a detailed description of its characteristics, summarizes the
      results of a feasibility study and four application studies in subjects having
      upper limb complex regional pain syndrome, discusses the most important
      practical, technical, and methodological issues that were encountered, and
      describes current and future research projects related to measuring (limitations
      of) upper limb activity.

PMID- 17186753
TI  - The use of digital video recorders (DVRs) for capturing digital video files for
      use in both The Observer and Ethovision.
AB  - Before switching a laboratory from analog to digital, for the recording of video
      files for use in Noldus software such as Ethovision and The Observer, researchers
      need to proceed with caution. There are obvious advantages in moving to digital
      recording for behavioral work, including increased storage capacity; no
      requirement to purchase video tapes; immediate search by date, time, or event;
      digital images are of higher quality; ability to view study sites remotely by
      Internet connection; and "smart" features, such as motion detection. But before
      you throw away your time-lapse video recorders, time code generators, and video
      multiplexors, there are some important cautions to take account of. Some research
      groups have bought digital surveillance systems on the assumption that they work
      with Ethovision and The Observer, only to be disappointed. The vast majority of
      systems depend on proprietary compression software that must then be converted to
      work properly in Ethovision or The Observer.

PMID- 17186755
TI  - How a visual surveillance system hypothesizes how you behave.
AB  - In the last few years, the installation of a large number of cameras has led to a
      need for increased capabilities in video surveillance systems. It has, indeed,
      been more and more necessary for human operators to be helped in the
      understanding of ongoing activities in real environments. Nowadays, the
      technology and the research in the machine vision and artificial intelligence
      fields allow one to expect a new generation of completely autonomous systems able
      to reckon the behaviors of entities such as pedestrians, vehicles, and so forth.
      Hence, whereas the sensing aspect of these systems has been the issue considered
      the most so far, research is now focused mainly on more newsworthy problems
      concerning understanding. In this article, we present a novel method for
      hypothesizing the evolution of behavior. For such purposes, the system is
      required to extract useful information by means of low-level techniques for
      detecting and maintaining track of moving objects. The further estimation of
      performed trajectories, together with objects classification, enables one to
      compute the probability distribution of the normal activities (e.g.,
      trajectories). Such a distribution is defined by means of a novel clustering
      technique. The resulting clusters are used to estimate the evolution of objects'
      behaviors and to speculate about any intention to act dangerously. The provided
      solution for hypothesizing behaviors occurring in real environments was tested in
      the context of an outdoor parking lot

PMID- 17186756
TI  - Behavioral phenotyping in zebrafish: comparison of three behavioral
      quantification methods.
AB  - The zebrafish has been popular in developmental biology and genetics, but its
      brain function has rarely been studied. High-throughput screening of mutation or
      drug-induced changes in brain function requires simple and automatable behavioral
      tests. This article compares three behavioral quantification methods in four
      simple behavioral paradigms that test a range of characteristics of adult
      zebrafish, including novelty-induced responses, social behavior, aggression, and
      predator-model-induced responses. Two quantification methods, manual recording
      and computerized videotracking of location and activity, yielded very similar
      results, suggesting that automated videotracking reliably measures activity
      parameters and will allow high-throughput screening. However, observation-based
      event recording of posture patterns was found generally not to correlate with
      videotracking measures, suggesting that further refinement of automated behavior
      quantification may be considered.

PMID- 17186757
TI  - Toward a rodent model of the Iowa gambling task.
AB  - The Iowa gambling task in humans is, in principle, suited for the study of the
      long-term efficiency of behavior in a biologically relevant context. Key features
      of this task are uncertainty of outcomes and a conflict between the immediate and
      the long-term payoff options. Animal models allow us to study the underlying
      neurobiology of decision-making processes and the long-term efficiency of
      behavior in more detail and at a greater depth than is possible in humans.
      Therefore, we set out to develop a model of this task in rodents, using the
      task's key features. In this article, we describe the results of the first series
      of experiments with rats and mice. The data thus far suggest that mice and rats
      behave in a way similar to humans; that is, they tend to choose the option with
      the best long-term payoff more often as the test progresses.

PMID- 17186758
TI  - Contactless measurement of cow behavior in a milking robot.
AB  - We have worked on automatically measuring the behavior of dairy cows during
      automatic milking. A milking robot offers a unique possibility for a dynamic
      measurement of physical data. Four strain gauge scales were installed into a
      milking robot in order to measure the weight of each leg separately, and a laser
      distance sensor was placed next to the robot in order to measure the radial
      movement of the cow's body surface. The data were collected into a PC. Three
      video cameras were installed to observe the system, and the data were recorded
      digitally. From the data, the dynamic weight or load of each leg and the
      respiration rate of a cow could be measured. Different stages of milking were
      observed, and the changes in behavior during milking were analyzed. The acquired
      information could be used to judge a cow's restlessness and welfare--for example,
      leg health and stress.

PMID- 17186759
TI  - An information theoretic measure for the evaluation of ordinal scale data.
AB  - This article describes a new measure of dispersion as an indication of consensus
      and dissention. Building on the generally accepted Shannon entropy, this measure
      utilizes a probability distribution and the ordered ranking of categories in an
      ordinal scale distribution to yield a value confined to the unit interval. Unlike
      other measures that need to be normalized, this measure is always in the interval
      0 to 1. The measure is typically applied to the Likert scale to determine degrees
      of agreement among ordinal-ranked categories when one is dealing with data
      collection and analysis, although other scales are possible. Using this measure,
      investigators can easily determine the proximity of ordinal data to consensus
      (agreement) or dissention. Consensus and dissention are defined relative to the
      degree of proximity of values constituting a frequency distribution on the
      ordinal scale measure. The authors identify a set of criteria that a measure must
      satisfy in order to be an acceptable indicator of consensus and show how the
      consensus measure satisfies all the criteria.

PMID- 17186760
TI  - Using ethnographic methods to carry out human factors research in software
      engineering.
AB  - This article describes how ethnographic methods were used to observe and analyze
      student teams working on software engineering (SE) projects. The aim of this
      research was to uncover the effects of the interplay of different personality
      types, as measured by a test based on the Myers-Briggs Type Indicator (MBTI), on
      the workings of an SE team. Using ethnographic methods allowed the researchers to
      record the effects of personality type on behavior toward teammates and how this
      related to the amount of disruption and positive ideas brought forward from each
      member, also examined in detail were issues that were either dogged by disruption
      or that did not have sufficient discussion devoted to them and the impact that
      they had on the outcomes of the project. Initial findings indicate that
      ethnographic methods are a valuable weapon to have in one's arsenal when carrying
      out research into human factors of SE.

PMID- 17186761
TI  - Psychophysiological analysis (PSPHA): a modular script-based program for
      analyzing psychophysiological data.
AB  - In psychophysiological research, complex tailor-made and interactive analyses of
      biosignals (e.g., skin conductance, heart rate, and respiration) are often
      required. Moreover, a synchronization between experimental stimuli and
      psychophysiolgical responses is necessary. In this article, we present
      Psychophysiological Analysis (PSPHA), a modular script-based program for
      analyzing biosignals in the time domain. The modules can be integrated in a
      VBScript, and a wizard allows easy adaption of parameters. PSPHA is a free,
      interactive, and flexible program for analyzing the data of psychophysiological
      experiments.

PMID- 17186762
TI  - Contact-free measurement of heart rate, respiration rate, and body movements
      during sleep.
AB  - We describe a noncontact method for the ambulant measurement of basic sleep
      physiology parameters in humans, particularly for field studies involving sleep
      research and sleep disturbances. This method traces the body movements,
      respiration, and heart action of a person at rest or asleep on a bed, using four
      high-resolution force sensors installed under the bedposts. The recoil movement
      of the body at each heartbeat, known as the cardioballistic effect, as well as
      the lifting and lowering of the thorax, while breathing, causes very small shifts
      o f the center of gravity of the bed andthe subject. These shifts arereflected in
      the altering forcedistributions across the four sensors. Cardiac and respiratory
      parameters and the subject's movement activity can be calculated from the sensor
      signals. Neither electrodes nor other kinds of transducers are in direct contact
      with the subject, which is the main advantage of this technique over conventional
      methods. Laboratory experiments were carried out to estimate validity and
      practicability. The method has been found to be adequate, especially for
      automated and unattended sleep-data collection over long periods of time.

PMID- 17186763
TI  - Water maze swim path analysis based on tracking coordinates.
AB  - In the Morris water maze, a task widely used to study spatial learning and memory
      in laboratory rodents, several parameters are employed to estimate cognitive
      abilities of animals by analyzing their swim path characteristics. An isolated
      view based on any one of these parameters is not always satisfactory, so
      multivariate procedures (factor analyses) are used to weight the parameters in
      context with the others. This method sheds light on some subtle differences in
      experimental animals' spatial memories or strategies. However, this approach has
      some subjective problems, because the definition of the parameters depends on the
      experimenter's opinion of appropriate measures; therefore, we suggest a bottom-up
      rather than a top-down analysis of swim paths by means of spatial coordinates. In
      the present study, swim paths were normalized to 100-element vectors and then
      subjected to a principal components analysis. Swim paths could be sufficiently
      described in terms of only three components, each of which accounted for specific
      characteristics of the trajectories. We found significant differences in swim
      path patterns between test groups of rats that could not be discriminated via
      standard water maze parameters. Thus, the components can be related to different
      aspects of spatial cognition not detectable by commonly used parameters.

PMID- 17186764
TI  - BatMon II: children's category norms for 33 categories.
AB  - Four hundred forty-eight children 3-12 years of age generated category exemplars
      for 33 distinct categories. The percentage of the participants reporting each
      exemplar, the percentage of the participants reporting each exemplar first, the
      percentage of the participants reporting each exemplar across age groups (3-5
      years, 6-8 years, and 9-12 years), and the mean rank of each exemplar are
      presented. A full version of the 29 category norms may be downloaded from
      www.psychonomic.org/archive.

PMID- 17186765
TI  - Using the open-source statistical language R to analyze the dichotomous Rasch
      model.
AB  - R, an open-source statistical language and data analysis tool, is gaining
      popularity among psychologists currently teaching statistics. R is especially
      suitable for teaching advanced topics, such as fitting the dichotomous Rasch
      model--a topic that involves transforming complicated mathematical formulas into
      statistical computations. This article describes R's use as a teaching tool and a
      data analysis software program in the analysis of the Rasch model in item
      response theory. It also explains thetheory behind, as well as an educator's
      goals for, fitting the Rasch model with joint maximum likelihood estimation. This
      article also summarizes the R syntax for parameter estimation and the calculation
      of fit statistics. The results produced by R is compared with the results
      obtained from MINISTEP and the output of a conditional logit model. The use of R
      is encouraged because it is free, supported by a network of peer researchers, and
      covers both basic and advanced topics in statistics frequently used by
      psychologists.

PMID- 17186766
TI  - SPSS and SAS programs for generalizability theory analyses.
AB  - The identification and reduction of measurement errors is a major challenge in
      psychological testing. Most investigators rely solely on classical test theory
      for assessing reliability, whereas most experts have long recommended using
      generalizability theory instead. One reason for the common neglect of
      generalizability theory is the absence of analytic facilities for this purpose in
      popular statistical software packages. This article provides a brief introduction
      to generalizability theory, describes easy to use SPSS, SAS, and MATLAB programs
      for conducting the recommended analyses, and provides an illustrative example,
      using data (N = 329) for the Rosenberg Self-Esteem Scale. Program output includes
      variance components, relative and absolute errors and generalizability
      coefficients, coefficients for D studies, and graphs of D study results.

PMID- 17186769
TI  - Using a Bayesian belief network model to categorize length of stay for radical
      prostatectomy patients.
AB  - A clinical pathway implements best medical practices and represents sequencing
      and timing of interventions by clinicians for a particular clinical presentation.
      We used a Bayesian belief network (BBN) to model a clinical pathway for radical
      prostatectomy and to categorize patient's length of stay (LOS) as being met or
      delayed given the patient's outcomes and activities. A BBN model constructed from
      historical data collected as part of a retrospective chart study represents
      probabilistic dependencies between specific events from the pathway and
      identifies events directly affecting LOS. Preliminary evaluation of a BBN model
      on an independent test sample of patients' data shows that model reliably
      categorizes LOS for the second and third day after the surgery (with overall
      accuracy of 82 and 84%, respectively).

PMID- 17186768
TI  - Observational study of operating room times for knee and hip replacement surgery
      at nine U.S. community hospitals.
AB  - Knee (N = 185) and hip (N = 140) replacement cases were studied at nine community
      hospitals in the midwestern United States to determine whether certain management
      interventions could decrease case durations and reduce labor costs. Substantive
      (10 min) reductions in operating room (OR) time per case were not associated
      with: 1) increases in OR staffing, such as the addition of a surgical assistant;
      2) complete elimination of all delays; or 3) increases in anesthesiologists'
      presence in the ORs. Substantive (10 min) increases in OR time per case were not
      associated with: 1) reductions in anesthesiologists' presence in the ORs or 2)
      changes in case scheduling to run fewer ORs, with some cases starting later in
      the day. Even if these factors had been associated with differences in OR time
      per case, any changes resulting from management interventions would still not
      have reduced labor costs. At these hospitals, OR nursing and anesthesia labor
      costs were fixed costs, because the OR workload averaged only 5.6 hr of cases per
      day.

PMID- 17186770
TI  - A mixture model approach to updating payment weights with an application to ICD
      10 implementation.

PMID- 17186767
TI  - A review of health care models for coronary heart disease interventions.
AB  - This article reviews models for the treatment of coronary heart disease (CHD).
      Whereas most of the models described were developed to assess the cost
      effectiveness of different treatment strategies, other models have also been used
      to extrapolate clinical trials, for capacity and resource planning, or to predict
      the future population with heart disease. In this paper we investigate the use of
      modelling techniques in relation to different types of health intervention, and
      we discuss the assumptions and limitations of these approaches. Many of the
      models reviewed in this paper use decision tree models for acute or short term
      interventions, and Markov or state transition models for chronic or long term
      interventions. Discrete event simulation has, however, been used for more complex
      whole system models, and for modelling resource-constrained interventions and
      operational planning. Nearly all of the studies in our review used cohort-based
      models rather than population based models, and therefore few models could
      estimate the likely total costs and benefits for a population group. Most studies
      used de novo purpose built models consisting of only a small number of health
      states. Models of the whole disease system were less common. The model
      descriptions were often incomplete. We recommend that the reporting of model
      structure, assumptions and input parameters is more explicit, to reduce the risk
      of biased reporting and ensure greater confidence in the model results.

PMID- 17186771
TI  - Cost-effectiveness of referrals to high-volume hospitals: an analysis based on a
      probabilistic Markov model for hip fracture surgeries.
AB  - Previous studies suggest that German hospitals that perform a high volume of hip
      fracture surgeries have a lower mortality rate and shorter length of stay than
      low-volume hospitals. The goal of this paper was to determine the long-term cost
      effectiveness (over 20 years) of referring hip fracture surgeries to high-volume
      hospitals, based on data from previous studies. From a societal perspective, the
      cost-effectiveness ratio was 15,530 Euro per QALY (quality-adjusted life year)
      (95% confidence interval 9,864-33,048 Euro), while total annual costs to the
      statutory health insurance amounted up to 19.6 million Euro. The referral of hip
      fracture surgeries to high-volume hospitals is thus likely to be cost-effective
      in Germany.

PMID- 17186772
TI  - An analysis of the pediatric vaccine supply shortage problem.
AB  - In 2002, several factors resulted in pediatric vaccine manufacturers not being
      able to produce a sufficient number of vaccines to vaccinate all the children in
      the United States according to the Recommended Childhood Immunization Schedule.
      The resulting vaccine supply shortage resulted in thousands of children not being
      fully immunized according to this schedule, and hence, created an unnecessary
      risk for epidemic outbreaks of several childhood diseases. The Centers for
      Disease Control and Prevention responded to this crisis by using pediatric
      vaccine stockpiles to mitigate the impact of future shortages. This paper
      presents a stochastic model that captures the vaccine supply during production
      interruptions. This model is used to assess the impact of pediatric vaccine
      stockpile levels on vaccination coverage rates, by considering the probability
      that all children can be immunized according to the Recommended Childhood
      Immunization Schedule over a given time period and the expected minimum vaccine
      supply. The model is also used to assess the proposed pediatric vaccine stockpile
      levels recommended by the United States Department of Health and Human Services.
      The results of this analysis suggest that the proposed vaccine stockpile levels
      are adequate to meet future vaccine production interruptions, provided that such
      production interruptions do not last more than six months (which is not
      surprising, given that is the time period for which they were designed). However,
      given that recent vaccine production interruptions have lasted (on average) for
      over one year, the proposed vaccine stockpile levels are insufficient to meet the
      nation's pediatric immunization needs during such time periods, which in turn
      could lead to localized and/or widespread disease outbreaks. Moreover, a moderate
      investment in higher vaccine stockpile levels would lead to a significantly
      reduced risk of such events.

PMID- 17186773
TI  - A network flow approach to optimizing hospital bed capacity decisions.
AB  - The delivery of cost-effective and quality hospital-based health care remains an
      important and ongoing challenge for the American health care industry. Despite
      numerous advances in medical procedures and technologies, a growing array of
      outpatient health care options, limits on inpatient reimbursements, and almost
      two decades of hospital contraction and consolidation, annual inpatient
      admissions in the United States are currently at levels not seen since the early
      1980s. This combination of increased demand and diminished resources makes
      planning for hospital bed capacity a difficult problem for health care decision
      makers. We examine this problem by developing a network flow model that
      incorporates facility performance and budget constraints to determine optimal
      hospital bed capacity over a finite planning horizon. Under modest assumptions,
      we demonstrate that for realistic sized capacity planning problems, our network
      formulation is not computationally intensive, and allows us to obtain optimal bed
      capacity plans quickly.

PMID- 17186774
TI  - [Essential polyenic fatty acids and blood pressure. Mechanisms of its
      physiological effect].

PMID- 17186775
TI  - [Gas liquid chromatographic determination of tricarbonic cycle acids in human
      plasma].
AB  - A procedure is proposed to identify non-volatile organic acids in small human
      plasma volumes by gas liquid chromatography (GLC), which shows a high degree of
      acid separation with the rather simplified preparation of samples. The principle
      of the procedure is deproteination, simultaneous perchloric acid neutralization,
      plasma lipid hydrolysis, transformation of the salts of carboxylic acids to free
      acids, and acid methylation. Acid GLC is performed on a gas chromatograph with a
      flame ionization detector, by using a 25-m x 0.2-mm column. The peaks are
      identified, by correlating the retention times for reference and plasma acids.
      Lactate, pyruvate, fumarate, malate, alpha-ketoglutarate, citrate, and isocitrate
      have been identified in the plasma samples.

PMID- 17186776
TI  - [Determination of serum valproic acid drugs by capillary electrophoresis].
AB  - Monitoring of valproates is caused by the nonlinear pharmacokinetics of the drugs
      and by the clinical effect-concentration dependence. Rapid and simple procedure
      has been developed to determine valproic acid in the serum and spinal fluid by
      capillary electrophoresis. Under the chosen conditions, the calibration curve is
      linear in the range of concentrations of 10 to 150 mg/l. The detection limit of
      valproate is 1.0 mg/ml. The accuracy of valproate determination was confirmed by
      the addition method. The findings were compared by the results of ion
      chromatographic determination that had been chosen as the reference technique.
      More than 80 serum samples from patients with epilepsy were analyzed.

PMID- 17186777
TI  - [Assessment of the results of determination of the blood level of
      dehydroepiandrosterone sulfate by using various commercial reagents].
AB  - The results of determination of the blood levels of dehydroepiandrosterone (DHEA)
      sulfate (DHEA-S) were comparatively assessed, by using the test systems "Steroid
      IEA-DHEA-sulfate" (ZAO "Alkor Bio" (Saint Petersburg, Russia)) and "DHEA-S ELISA
      ("DRG Instruments GmbH (Germany)). The studies were conducted in apparently
      healthy 19-59-year-old women living in the middle belt of Western Siberia. They
      revealed the high sensitivity of the study test systems to age-related changes in
      the blood concentration of DHEA-S. The normal blood DHEA-S concentrations levels
      given in the instruction to the "DHEA-S ELISA" test systems were found to be
      decreased in they are used to measure the content of the above analyzed parameter
      in women aged 19-39 years.

PMID- 17186779
TI  - [Photometric measurements during biochemical laboratory studies (a lecture)].

PMID- 17186778
TI  - [The plasma levels of malonic dialdehyde and ceruloplasmin in patients with
      salmonellosis].

PMID- 17186780
TI  - [Analysis of the amount of plasma cholesterol and triglycerides in patients with
      coronary heart disease].
AB  - Fluorescence technique was used to study the time course of changes in the amount
      of blood cholesterol and triglycerides (C+TG) in 43 patients with Q- and non-Q
      wave myocardial infarction (MI) on days 1, 2, 3, and 10 of the disease, in 82
      patients with chronic coronary heart disease (CHD), and in 43 apparently healthy
      donors. Within the first 3 days of the disease, the level of C+TG in the patients
      with acute MI (AMI) was significantly lower than that in the patients with
      chronic CHD and in the donors. By day 10 of their hospital stay, the level of
      lipids in patients with AMI increased and reached the levels observed in the
      control group.

PMID- 17186781
TI  - [Immunogenodiagnosis and postinfection immunodeficiency syndrome in a hospital
      doctor's practice (a review of literature)].

PMID- 17186782
TI  - [Use of a scanner to register the results of enzyme immunoassay in the standard
      microplates].
AB  - Whether a commercially available scanner might be used as a vertical photometer
      of 96-well microplates for enzyme immunoassay (EIA) was studied. The analytical
      characteristics of the scanner in this regard were assessed, by comparing the
      findings with the respective photometric data obtained by a "VICTOR" EIA
      analyzer. It is concluded that the scanner registration system in combination
      with "Expert-Lab EIA" may be used in all types of EIA. The scanner system
      provides additional possibilities as compared with the conventional photometric
      analyzers.

PMID- 17186783
TI  - [Use of an immunoblot in the diagnosis of lingering forms of Yersinia infections
      and in the study of its pathogenesis (a review of literature)].

PMID- 17186784
TI  - [Serum nitric oxide as an additional criterion for evaluating the course of
      leptospirosis].
AB  - The blood level of nitric oxide (NO) was studied during an infectious process in
      107 patients with leptospirosis. The content of NO was estimated from the level
      of the final stable nitrogen cycle metabolite--nitrite was estimated by the Griss
      reaction. Infectious toxic shock (57%), disseminated intravascular coagulation
      syndrome (31%), respiratory distress syndrome (36%), and acute renal and hepatic
      failure (76%) were observed in the examinees. A combination of 3-4 of the above
      abnormalities was noted in 49% of the patients. There were elevated blood nitrite
      levels at the onset of the disease in patients with leptospirosis with signs of
      infectious toxic shock (15.3+/-2.79 micromol/l). In patients with a poor or
      complicated rehabilitative period, the high levels of nitrite were retained or
      its concentration repeatedly increased at weeks 3-4 of the disease. It has been
      shown that the measurements of blood nitrite levels may be used as an additional
      diagnostic criterion for evaluating the course of leptospirosis.

PMID- 17186785
TI  - Mass destruction.

PMID- 17186786
TI  - What is your diagnosis? Aquagenic syringeal acrokeratoderma (ASA).

PMID- 17186787
TI  - Localized argyria after exposure to aerosolized solder.
AB  - GOAL: To understand localized argyria to better manage patients with the
      condition OBJECTIVES: Upon completion of this activity, dermatologists and
      general practitioners should be able to: 1. Discuss how localized and generalized
      argyria differ. 2. Describe how to diagnose argyria. 3. Identify treatment
      options for argyria.

PMID- 17186788
TI  - Tuberculosis verrucosa cutis presenting as an annular hyperkeratotic plaque.
AB  - GOAL: To understand cutaneous tuberculosis to better manage patients with the
      condition OBJECTIVES: Upon completion of this activity, dermatologists and
      general practitioners should be able to: 1. Recognize the morphologic features of
      cutaneous tuberculosis. 2. Describe the histopathologic characteristics of
      cutaneous tuberculosis. 3. Explain the treatment options for cutaneous
      tuberculosis.

PMID- 17186789
TI  - Thrombogenic vasculopathy with diffuse neutrophilic inflammation: a histologic
      manifestation of a tick bite.
AB  - We describe 5 cases of tick bite reactions with dermal necrosis and sparse
      interstitial to dense diffuse dermal neutrophilic infiltrates associated with
      thrombogenic vasculopathy. Tick bite reactions classically consist of moderately
      dense perivascular infiltrates composed of an admixture of inflammatory cells.
      Each of our patients had embedded tick parts, with interesting histologic
      features.

PMID- 17186790
TI  - Localized chronic fibrosing vasculitis causing a rhinophymatous eruption.
AB  - We describe a patient with localized chronic fibrosing vasculitis who presented
      with a rhinophymalike eruption of the nose. To our knowledge, the manifestation
      of this condition on the nose has not been previously reported. The differential
      diagnosis also is examined.

PMID- 17186791
TI  - Reticular telangiectatic erythema associated with an implantable cardioverter
      defibrillator.
AB  - Reticular telangiectatic erythema (RTE) is a skin reaction associated with
      implantable cardiac devices (ie, pacemakers and cardioverter defibrillators). We
      present a patient who developed an erythematous patch over the implantable
      cardioverter defibrillator site. We discuss the clinical features, histologic
      findings, and patch testing of this entity.

PMID- 17186792
TI  - Helping children cope with hair loss.
AB  - Alopecia totalis and alopecia universalis are emotionally devastating forms of
      hair loss, which are difficult to cure. When childhood hair loss is unresponsive
      to alopecia therapies, both traditional and nontraditional, children may be
      stigmatized and fall under extreme psychologic distress. The not-for-profit
      organization Locks of Love began providing custom hair prostheses to children in
      1997 and has continued to serve the emotional and cosmetic needs of children with
      extensive hair loss.

PMID- 17186793
TI  - Fixed cutaneous sporotrichosis in an adolescent boy: a case report.
AB  - We present a case of an adolescent boy with a 3-week history of 3 painless
      purulent erythematous ulcers with raised hyperkeratotic borders associated with
      regional lymphadenopathy on the medial aspect of the right antecubital fossa.
      There were no known initiating factors and no other significant associated signs
      or symptoms. The patient initially was treated with antibiotics, with no
      improvement. Bacterial and fungal cultures of biopsy specimens demonstrated the
      presence of Sporothrix schenckii and confirmed the diagnosis of sporotrichosis.
      Itraconazole was initiated with an appropriate response. This case demonstrates
      the importance of understanding the clinical presentation of sporotrichosis in
      children without a history of the disease.

PMID- 17186794
TI  - Adult-onset tufted angioma: a case report and review of the literature.
AB  - Tufted angiomas (TAs) are benign vascular tumors, primarily occurring on the
      trunk and extremities of children younger than 5 years. Few cases occurring on
      the oral mucosa and in adults have been reported. Although they are typically
      isolated lesions, TA has been associated with port-wine stains. We describe a
      case of adult-onset TA on the lower lip mucosa.

PMID- 17186797
TI  - Cognitive and smart adaptation in computer-communication networks.

PMID- 17186795
TI  - Evaluation of the efficacy and safety of clobetasol propionate spray in the
      treatment of plaque-type psoriasis.
AB  - Treatment of the inflammatory component of plaque psoriasis is an important part
      of psoriasis management. A new and unique spray formulation of clobetasol
      propionate 0.05% may provide advantages over the currently available formulations
      through easy application to hard-to-reach areas and the ability to deliver a
      fixed dose of corticosteroid per spray. The purpose of this study was to evaluate
      the efficacy and safety of clobetasol propionate spray 0.05% in the treatment of
      moderate to severe plaque-type psoriasis. This study was conducted as a
      multicenter, randomized, double-blinded, vehicle-controlled, parallel-group,
      comparative study in subjects with plaque psoriasis. Subjects were randomized to
      receive either clobetasol propionate spray 0.05% (n=60) or vehicle spray (n=60)
      twice daily for 4 weeks, followed by a 4-week treatment-free follow-up period.
      Efficacy evaluations at all visits included assessment of scaling, erythema,
      plaque elevation, pruritus, and overall disease severity. Success rates for each
      of the signs and symptoms evaluated, as well as for the overall disease severity
      assessment, were significantly in favor of clobetasol propionate (P<.001). The
      additional 2 weeks of treatment from weeks 2 to 4 increased the number of cleared
      subjects from 2% to 25%; treatment success was still in favor of clobetasol
      propionate (P<.001) at week 8 (4 weeks post-treatment). No treatment-related
      serious adverse events occurred during the course of the study. Mild application
      site burning/stinging was the most common treatment-related adverse event, with
      similar frequency and severity for both active and vehicle groups. There were no
      reports of skin atrophy, telangiectasia, folliculitis, or hypothalamus-pituitary
      adrenal axis suppression. Overall, clobetasol propionate spray 0.05% administered
      twice daily for 4 weeks was effective and safe in reducing scaling, erythema,
      plaque elevation, and overall disease severity and demonstrates durable clinical
      response up to 4 weeks after treatment end.

PMID- 17186798
TI  - Self-adaptation in next-generation Internet networks: how to react to traffic
      changes while respecting QoS?
AB  - Next-generation network infrastructure should support different services and
      several levels of quality of service (QoS) and resilience. The main requirements
      for such multiservice networks are flexibility, effective utilization of network
      resources, and ability to react to traffic demand changes with time. These
      requisites lead to the fact that next-generation networks should, to some extend,
      be "self-adapting," to cope with the need of promptly reacting to traffic demand
      changes, in an effective way, while taking into account the different
      requirements in terms of QoS. This paper sketches the reference network scenario
      and discusses the subject of self-adapting networks, attempting to focus on the
      key issues that need to be solved to realize future infrastructures. As a
      relevant example, this paper briefly reports a system developed by the authors'
      laboratory that implements a traffic engineering solution able to fulfill the
      mentioned requirements. This system could be regarded as a first concrete step
      toward the realization of self-adapting networks. In addition, some relevant
      results that were obtained either by simulation or by experiments on a real test
      bed are reported to discuss the main characteristics of such a system and assess
      the feasibility of the concept. Finally, the paper reviews the main hot issues
      that need to be addressed, in the authors' opinion, by the international research
      community.

PMID- 17186796
TI  - Desoximetasone 0.25% and tacrolimus 0.1% ointments versus tacrolimus alone in the
      treatment of atopic dermatitis.
AB  - Long-term in vitro compatibility of desoximetasone and tacrolimus ointments
      prompted the current trial in humans. We aimed to evaluate the efficacy of twice
      daily simultaneous application of desoximetasone and tacrolimus in the treatment
      of atopic dermatitis versus tacrolimus monotherapy. Eighty-two subjects were
      treated in this multicenter, single-group, double-blinded, paired, 3-week follow
      up clinical study of desoximetasone 0.25% and tacrolimus 0. 1% ointments versus
      tacrolimus 0.1% ointment and vehicle. Subjects were treated twice daily for 21
      days or until clearing. Safety and efficacy were assessed at days 3, 7, 14, and
      21. The combination of desoximetasone and tacrolimus ointment was superior to
      tacrolimus alone (P=.0002) in treating atopic dermatitis as measured by the
      summary of the scores for erythema, lichenification, pruritus, scaling/dryness,
      and oozing/crusting. Of note, pruritus at the application site was diminished in
      subjects treated with desoximetasone and tacrolimus together compared with
      tacrolimus alone (P=.04). Combination treatment with desoximetasone and
      tacrolimus offered increased efficacy and tolerability over tacrolimus alone in
      patients with atopic dermatitis.

PMID- 17186799
TI  - Self-organizing and adaptive peer-to-peer network.
AB  - In this paper, an algorithm that forms a dynamic and self-organizing network is
      demonstrated. The hypothesis of this work is that in order to achieve a resilient
      and adaptive peer-to-peer (P2P) network, each network node must proactively
      maintain a minimum number of edges. Specifically, low-level communication
      protocols are not sufficient by themselves to achieve high-service availability,
      especially in the case of ad hoc or dynamic networks with a high degree of node
      addition and deletion. The concept has been evaluated within a P2P agent
      application in which each agent has a goal to maintain a preferred number of
      connections to a number of service providing agents. Using this algorithm, the
      agents update a weight value associated with each connection, based on the
      perceived utility of the connection to the corresponding agent. This utility
      function can be a combination of several node or edge parameters, such as degree
      k of the target node, or frequency of the message response from the node. This
      weight is updated using a set of Hebbian-style learning rules, such that the
      network as a whole exhibits adaptive self-organizing behavior. The principal
      result is the finding that by limiting the connection neighborhood within the
      overlay topology, the resulting P2P network can be made highly resilient to
      targeted attacks on high-degree nodes, while maintaining search efficiency.

PMID- 17186800
TI  - Self-organized service orchestration through collective differentiation.
AB  - This paper shows how self-(*) mechanisms give rise to complex but predictable and
      therefore steerable global system behavior in a cooperative computing
      environment. The operation of and the interactions between a set of networked
      autonomic devices are simulated. These are used as access points to a number of
      services, have the ability to accept or delegate execution of the associated
      tasks, and can adjust their internal state in response to the demand. At
      initialization, all devices are assigned a random internal state, i.e., there is
      no correlation between their configuration and the tasks that they are expected
      to perform. The authors study the emergence of cooperation and find that it
      spontaneously occurs when specific conditions are met, which allow individual
      devices to focus on performing a single task, sacrificing their ability to
      efficiently perform others. A relatively simple model that can be completely and
      thoroughly analyzed was chosen so as to demonstrate how the methodology developed
      to study complex adaptive systems in biology can be a powerful tool when planning
      the deployment of large ensembles of interacting autonomic devices.

PMID- 17186801
TI  - Genetic algorithms for route discovery.
AB  - Packet routing in networks requires knowledge about available paths, which can be
      either acquired dynamically while the traffic is being forwarded, or statically
      (in advance) based on prior information of a network's topology. This paper
      describes an experimental investigation of path discovery using genetic
      algorithms (GAs). We start with the quality-of-service (QoS)-driven routing
      protocol called "cognitive packet network" (CPN), which uses smart packets (SPs)
      to dynamically select routes in a distributed autonomic manner based on a user's
      QoS requirements. We extend it by introducing a GA at the source routers, which
      modifies and filters the paths discovered by the CPN. The GA can combine the
      paths that were previously discovered to create new untested but valid source-to
      destination paths, which are then selected on the basis of their "fitness." We
      present an implementation of this approach, where the GA runs in background mode
      so as not to overload the ingress routers. Measurements conducted on a network
      test bed indicate that when the background-traffic load of the network is light
      to medium, the GA can result in improved QoS. When the background-traffic load is
      high, it appears that the use of the GA may be detrimental to the QoS experienced
      by users as compared to CPN routing because the GA uses less timely state
      information in its decision making.

PMID- 17186802
TI  - Linear QoS goals of additive and concave metrics in ad hoc cognitive packet
      routing.
AB  - This paper addresses two scalability problems related to the cognitive map of
      packets in ad hoc cognitive packet networks and proposes a solution. Previous
      works have included latency as part of the routing goal of smart packets, which
      requires packets to collect their arrival time at each node in a path. Such a
      requirement resulted in a packet overhead proportional to the path length. The
      second problem is that the multiplicative form of path availability, which was
      employed to measure resources, loses accuracy in long paths. To solve these
      problems, new goals are proposed in this paper. These goals are linear functions
      of low-overhead metrics and can provide similar performance results with lower
      cost. One direct result shown in simulation is that smart packets driven by a
      linear function of path length and buffer occupancy can effectively balance the
      traffic of multiple flows without the large overhead that would be needed if
      round-trip delay was used. In addition, energy-aware routing is also studied
      under this scheme as well as link selection based on their expected level of
      security.

PMID- 17186803
TI  - Continuous-time negotiation mechanism for software agents.
AB  - While there are several existing mechanisms and systems addressing the crucial
      and difficult issues of automated one-to-many negotiation, this paper develops a
      flexible one-to-many negotiation mechanism for software agents. Unlike the
      existing general one-to-many negotiation mechanism, in which an agent should wait
      until it has received proposals from all its trading partners before generating
      counterproposals, in the flexible one-to-many negotiation mechanism, an agent can
      make a proposal in a flexible way during negotiation, i.e., negotiation is
      conducted in continuous time. To decide when to make a proposal, two strategies
      based on fixed waiting time and a fixed waiting ratio are proposed. Results from
      a series of experiments suggest that, guided by the two strategies for deciding
      when to make a proposal, the flexible negotiation mechanism achieved more
      favorable trading outcomes as compared with the general one-to-many negotiation
      mechanism. To determine the amount of concession, negotiation agents are guided
      by four mathematical functions based on factors such as time, trading partners'
      strategies, negotiation situations of other threads, and competition.
      Experimental results show that agents guided by the four functions react to
      changing market situations by making prudent and appropriate rates of concession
      and achieve generally favorable negotiation outcomes.

PMID- 17186804
TI  - Rotation-invariant texture image retrieval using rotated complex wavelet filters.
AB  - This paper proposes a novel approach for rotation-invariant texture image
      retrieval by using set of dual-tree rotated complex wavelet filter (DT-RCWF) and
      DT complex wavelet transform (DT-CWT) jointly, which obtains texture features in
      12 different directions. Two-dimensional RCWFs are nonseparable and oriented,
      which improves characterization of oriented textures. Robust and efficient
      isotropic rotationally invariant features are extracted from DT-RCWF and DT-CWT
      decomposed subbands. This paper demonstrates the effectiveness of this new set of
      features on four different sets of rotated and nonrotated databases. Experimental
      results indicate that the proposed method improves retrieval accuracy from 83.17%
      to 93.71% on a small size (208 images) nonrotated database D1, from 82.71% to
      90.86% on a small size (208 images) rotated database D2, from 72.18% to 76.09% on
      a medium-size (640 images) rotated database D3, and from 64.17% to 78.93% on a
      large size (1856 images) rotated database D4, compared with the discrete wavelet
      transform-based approach. New method also retains comparable levels of
      computational complexity.

PMID- 17186805
TI  - Structured one-class classification.
AB  - The one-class classification problem aims to distinguish a target class from
      outliers. The spherical one-class classifier (SOCC) solves this problem by
      finding a hypersphere with minimum volume that contains the target data while
      keeping outlier samples outside. SOCC achieves satisfactory performance only when
      the target samples have the same distribution tendency in all orientations.
      Therefore, the performance of the SOCC is limited in the way that many
      superfluous outliers might be mistakenly enclosed. The authors propose to exploit
      target data structures obtained via unsupervised methods such as agglomerative
      hierarchical clustering and use them in calculating a set of hyperellipsoidal
      separating boundaries. This method is named the structured one-class classifier
      (TOCC). The optimization problem in TOCC can be formulated as a series of second
      order cone programming problems that can be solved with acceptable efficiency by
      primal-dual interior-point methods. The experimental results on artificially
      generated data sets and benchmark data sets demonstrate the advantages of TOCC.

PMID- 17186806
TI  - Topology description for data distributions using a topology graph with divide
      and-combine learning strategy.
AB  - The topologies of data distributions are very important for data description.
      Usually, it is not easy to find a description that can give us an intuitional
      understanding of the topologies for general distributions. In this paper, a novel
      concept, a topology graph, is proposed as a description for the principal
      topology of data distribution. The topology graph builds a one-to-one
      correspondence between the principal topology of the distribution and the
      topology itself: annularity features of the principal topology correspond to the
      loops of the graph, and the divarication features correspond to the branches of
      the graph. In general, the topology graph can be considered as the skeleton of
      the data distribution. A divide-and-combine learning strategy is developed to
      find the topology graphs for general data distributions. The learning strategy is
      focused on the constrained local description learning and automatic topology
      generation. Following the learning strategy, a cluster growing algorithm is
      developed. Experimental results on both artificial datasets and real-world
      applications show good performance of the proposed algorithm.

PMID- 17186807
TI  - Customized generalization of support patterns for classification.
AB  - We propose a novel classification learning method called customized support
      pattern learner (CSPL). Given an instance to be classified, CSPL explores and
      discovers support patterns (SPs), which are essentially attribute value subsets
      of the instance to be classified. The final prediction of the class label is
      performed by combining some statistics of the discovered useful SPs. One
      advantage of the CSPL method is that it can explore a richer hypothesis space and
      discover useful classification patterns involving attribute values with almost
      indistinguishable information gain. The customized learning characteristic also
      allows that the target class can vary for different instances to be classified.
      It facilitates extremely easy training instance maintenance and updates. We have
      evaluated our method with real-world problems and benchmark data sets. The
      results demonstrate that CSPL can achieve good performance and high reliability.

PMID- 17186808
TI  - CATSMLP: toward a robust and interpretable multilayer perceptron with sigmoid
      activation functions.
AB  - Enhancing the robustness and interpretability of a multilayer perceptron (MLP)
      with a sigmoid activation function is a challenging topic. As a particular MLP,
      additive TS-type MLP (ATSMLP) can be interpreted based on single-stage fuzzy IF
      THEN rules, but its robustness will be degraded with the increase in the number
      of intermediate layers. This paper presents a new MLP model called cascaded
      ATSMLP (CATSMLP), where the ATSMLPs are organized in a cascaded way. The proposed
      CATSMLP is a universal approximator and is also proven to be functionally
      equivalent to a fuzzy inference system based on syllogistic fuzzy reasoning.
      Therefore, the CATSMLP may be interpreted based on syllogistic fuzzy reasoning in
      a theoretical sense. Meanwhile, due to the fact that syllogistic fuzzy reasoning
      has distinctive advantage over single-stage IF-THEN fuzzy reasoning in
      robustness, this paper proves in an indirect way that the CATSMLP is more robust
      than the ATSMLP in an upper-bound sense. Several experiments were conducted to
      confirm such a claim.

PMID- 17186809
TI  - Maximal class of weakly live ordinary Petri nets without emptiable siphons.
AB  - It is known that a net is deadlock free, not necessarily live, if no siphons can
      become empty. The key structure in making some transitions not live is called
      virtual first-order structure (VFOS). A net with (without) VFOS is called a
      virtual net (V net) [nonvirtual net (NV net)]. The V net is a maximal class of
      nets that may be weakly live and not live, if no siphons can become empty. Any
      net in the NV nets is live if and only if no siphons can become empty. In this
      paper, it is shown that asymmetric choice nets, synchronized choice nets, and
      extended synchronized choice nets belong to the NV nets.

PMID- 17186810
TI  - Adaptive dynamic surface control of flexible-joint robots using self-recurrent
      wavelet neural networks.
AB  - A new method for the robust control of flexible-joint (FJ) robots with model
      uncertainties in both robot dynamics and actuator dynamics is proposed. The
      proposed control system is a combination of the adaptive dynamic surface control
      (DSC) technique and the self-recurrent wavelet neural network (SRWNN). The
      adaptive DSC technique provides the ability to overcome the "explosion of
      complexity" problem in backstepping controllers. The SRWNNs are used to observe
      the arbitrary model uncertainties of FJ robots, and all their weights are trained
      online. From the Lyapunov stability analysis, their adaptation laws are induced,
      and the uniformly ultimately boundedness of all signals in a closed-loop adaptive
      system is proved. Finally, simulation results for a three-link FJ robot are
      utilized to validate the good position tracking performance and robustness
      against payload uncertainties and external disturbances of the proposed control
      system.

PMID- 17186811
TI  - Robust stability of switched Cohen-Grossberg Neural networks with mixed time
      varying delays.
AB  - By combining Cohen-Grossberg neural networks with an arbitrary switching rule,
      the mathematical model of a class of switched Cohen-Grossberg neural networks
      with mixed time-varying delays is established. Moreover, robust stability for
      such switched Cohen-Grossberg neural networks is analyzed based on a Lyapunov
      approach and linear matrix inequality (LMI) technique. Simple sufficient
      conditions are given to guarantee the switched Cohen-Grossberg neural networks to
      be globally asymptotically stable for all admissible parametric uncertainties.
      The proposed LMI-based results are computationally efficient as they can be
      solved numerically using standard commercial software. An example is given to
      illustrate the usefulness of the results.

PMID- 17186812
TI  - On impact dynamics and contact events for biped robots via impact effects.
AB  - In this paper, impact dynamics of a five-link biped walking on level ground are
      studied, and the results are used to correlate the gait parameters with the
      contact event following impact. The conventional five-link biped kinematic model
      is improved such that, for the first time, the explicit solution for the external
      impulses is obtained in a detailed but compact form. Such a solution reveals that
      the direction of the swing tip velocity prior to impact is a key factor dictating
      the upcoming contact event and the slippage. The conventional conditions to
      warrant the types of impact are expanded to make them sufficient. The
      aforementioned results are used in the parametric analysis to predict the contact
      event after impact. Such a prediction is important for proper dynamic modeling,
      motion planning, and control of the upcoming supporting phase.

PMID- 17186813
TI  - Qualitative visual environment retrieval.
AB  - A system for retrieval of an unstructured environment under static and dynamic
      scenarios is proposed. The use of cylindrical mosaics or omnidirectional images
      is exploited for providing a rich description about the surrounding environment
      spanning 360 degrees. The environment description is based on defining the
      attributes of the nodes of a graph derived from the angular partitions of the
      captured images. Content-based image retrieval for each of these partitions is
      performed on an exemplar image database to annotate the nodes of the graph. The
      complete environment description is recovered by collating the retrieval results
      over all the partitions based on a simple voting scheme. This offers a
      qualitative description of the location in a totally natural and unstructured
      surrounding. The experiments yield quite promising results.

PMID- 17186814
TI  - Grid commerce, market-driven G-negotiation, and Grid resource management.
AB  - Although the management of resources is essential for realizing a computational
      grid, providing an efficient resource allocation mechanism is a complex
      undertaking. Since Grid providers and consumers may be independent bodies,
      negotiation among them is necessary. The contribution of this paper is showing
      that market-driven agents (MDAs) are appropriate tools for Grid resource
      negotiation. MDAs are e-negotiation agents designed with the flexibility of: 1)
      making adjustable amounts of concession taking into account market rivalry,
      outside options, and time preferences and 2) relaxing bargaining terms in the
      face of intense pressure. A heterogeneous testbed consisting of several types of
      e-negotiation agents to simulate a Grid computing environment was developed. It
      compares the performance of MDAs against other e-negotiation agents (e.g.,
      Kasbah) in a Grid-commerce environment. Empirical results show that MDAs
      generally achieve: 1) higher budget efficiencies in many market situations than
      other e-negotiation agents in the testbed and 2) higher success rates in
      acquiring Grid resources under high Grid loadings.

PMID- 17186815
TI  - Classification using belief functions: relationship between case-based and model
      based approaches.
AB  - The transferable belief model (TBM) is a model to represent quantified
      uncertainties based on belief functions, unrelated to any underlying probability
      model. In this framework, two main approaches to pattern classification have been
      developed: the TBM model-based classifier, relying on the general Bayesian
      theorem (GBT), and the TBM case-based classifier, built on the concept of
      similarity of a pattern to be classified with training patterns. Until now, these
      two methods seemed unrelated, and their connection with standard classification
      methods was unclear. This paper shows that both methods actually proceed from the
      same underlying principle, i.e., the GBT, and that they essentially differ by the
      nature of the assumed available information. This paper also shows that both
      methods collapse to a kernel rule in the case of precise and categorical learning
      data and for certain initial assumptions, and a simple relationship between basic
      belief assignments produced by the two methods is exhibited in a special case.
      These results shed new light on the issues of classification and supervised
      learning in the TBM. They also suggest new research directions and may help users
      in selecting the most appropriate method for each particular application,
      depending on the nature of the information at hand.

PMID- 17186816
TI  - Coevolutionary particle swarm optimization using Gaussian distribution for
      solving constrained optimization problems.
AB  - In this correspondence, an approach based on coevolutionary particle swarm
      optimization to solve constrained optimization problems formulated as min-max
      problems is presented. In standard or canonical particle swarm optimization
      (PSO), a uniform probability distribution is used to generate random numbers for
      the accelerating coefficients of the local and global terms. We propose a
      Gaussian probability distribution to generate the accelerating coefficients of
      PSO. Two populations of PSO using Gaussian distribution are used on the
      optimization algorithm that is tested on a suite of well-known benchmark
      constrained optimization problems. Results have been compared with the canonical
      PSO (constriction factor) and with a coevolutionary genetic algorithm. Simulation
      results show the suitability of the proposed algorithm in terms of effectiveness
      and robustness.

PMID- 17186817
TI  - A fast procedure for optimizing dynamic force distribution in multifingered
      grasping.
AB  - This correspondence deals with the dynamic force distribution (DFD) problem,
      i.e., computing the contact forces to equilibrate a dynamic external wrench on
      the grasped object. The sum of the normal force components is minimized for
      enhancing safety and saving energy. By this optimality criterion, the DFD problem
      can be transformed into a linear programming (LP) problem. Its objective function
      is the inner product of the dynamic external wrench and a vector, and the
      constraints on the vector, given by a set of linear inequalities, define a
      polytope. The solution to the LP problem can always be attained at the vertex of
      the polytope called the solution vertex. We notice that the polytope is
      determined by the grasp configuration. Along with the direction change of the
      dynamic external wrench, only the solution vertex moves to an adjacent vertex
      sequentially, whereas the polytope with all its vertices remains unchanged.
      Therefore, the polytope and the adjacencies of each vertex can be computed in the
      offline phase. Then, in the online phase, simply search the adjacencies of the
      old solution vertex for the new one. Without lost of optimality, such a DFD
      algorithm runs a thousandfold faster than solving the LP problem by the simplex
      method in real time.

PMID- 17186818
TI  - Design of PI observers for continuous-time descriptor linear systems.
AB  - A parametric design approach for proportional-integral (PI) observers for
      continuous-time descriptor linear systems is proposed based on a complete general
      parametric solution to the generalized Sylvester matrix equation. The proposed
      approach provides complete parameterizations for all the observer gain matrices,
      gives the parametric expression for the corresponding finite left eigenvector
      matrix of the observer system matrix, realizes elimination of impulsive
      responses, and guarantees the regularity of the observer system. The design
      method offers all the degrees of design freedom, which can be utilized to achieve
      various desired system specifications and performances and, thus, has great
      potentials in applications. A numerical example is employed to show the design
      procedure and illustrate the effect of the proposed approach. Simulation results
      show a satisfactory tracking performance for descriptor linear systems.

PMID- 17186819
TI  - Rendezvous-guidance trajectory planning for robotic dynamic obstacle avoidance
      and interception.
AB  - This correspondence presents a novel online trajectory-planning method for the
      autonomous robotic interception of moving targets in the presence of dynamic
      obstacles, i.e., position and velocity matching (also referred to as rendezvous).
      The proposed time-optimal interception method is a hybrid algorithm that augments
      a novel rendezvous-guidance (RG) technique with the velocity-obstacle approach,
      for obstacle avoidance, first reported by Fiorini and Shiller. The obstacle
      avoidance algorithm itself could not be used in its original form and had to be
      modified to ensure that the online planned path deviates minimally from the one
      generated by the RG algorithm. Extensive simulation and experimental analyses,
      some of which are reported in this correspondence, have clearly demonstrated the
      tangible time efficiency of the proposed interception method.

PMID- 17186820
TI  - Variable-gain controllers for nonlinear systems using the T-S fuzzy model.
AB  - This correspondence proposes two novel control schemes with variable state
      feedback gain to stabilize a Takagi-Sugeno (T-S) fuzzy system. The T-S fuzzy
      model is expressed as a linear plant with nonlinear disturbance terms in both
      schemes. In controller I, the T-S fuzzy model is expressed as a linear plant
      around a nominal plant arbitrarily selected from the set of linear subsystems
      that the T-S fuzzy model consists of. The variable gain then becomes a function
      of a gain parameter that is computed to neutralize the effect of disturbance
      term, which is, in essence, the deviation of the actual system dynamics from the
      nominal plant as the system traverses a specific trajectory. This controller is
      shown to stabilize the T-S fuzzy model. In controller II, individual linear
      subsystems are locally stabilized. Fuzzy blending of individual control actions
      is shown to make the T-S fuzzy system Lyapunov stable. Although applicability of
      both control schemes depends on the norm bound of unmatched state disturbance,
      this constraint is relaxed further in controller II. The efficacy of controllers
      I and II has been tested on two nonlinear systems.

PMID- 17186822
TI  - Kim's big fizzle.

PMID- 17186821
TI  - Meet resistance head-on.

PMID- 17186823
TI  - Seismic sentries.

PMID- 17186825
TI  - Seeing stars in Iraq.

PMID- 17186824
TI  - Pollution in solution.

PMID- 17186826
TI  - Here come the X-mice.

PMID- 17186827
TI  - Real stinkers reformed.

PMID- 17186828
TI  - Teen sex in America.

PMID- 17186829
TI  - Airborne baloney.

PMID- 17186830
TI  - The neglected tropical diseases.

PMID- 17186831
TI  - What is a planet?

PMID- 17186832
TI  - Is ethanol for the long haul?

PMID- 17186833
TI  - The power of riboswitches.

PMID- 17186834
TI  - A robot in every home.

PMID- 17186836
TI  - The Mississippi's curious origins.

PMID- 17186835
TI  - Evolved for cancer?

PMID- 17186837
TI  - Better ways to target pain.

PMID- 17186838
TI  - Physiologic VDD versus nonphysiologic VVI pacing in canine 3rd degree
      atrioventricular block.

PMID- 17186839
TI  - Diagnosis of DIC in cats: is it time to go back to the basics?

PMID- 17186840
TI  - Effects of deracoxib or buffered aspirin on the gastric mucosa of healthy dogs.
AB  - BACKGROUND: Use of cyclo-oxygenase-2 specific nonsteroidal anti-inflammatory
      drugs such as deracoxib has been advocated because of their anti-inflammatory
      actions and apparently low incidence of gastrointestinal adverse effects.
      HYPOTHESIS: Deracoxib will cause less endoscopically detectable gastric injury in
      dogs than aspirin, a nonselective nonsteroidal anti-inflammatory drug. ANIMALS:
      Twenty-four random source healthy dogs. METHODS: A randomized, placebo-controlled
      trial compared gastroscopic findings of dogs receiving placebo (q8h), aspirin (25
      mg/kg PO q8h), or deracoxib (1.5 mg/kg QD, placebo ql2h) for 28 days. Gastroscopy
      on days -7, 6, 14, and 28 evaluated 4 regions of the stomach separately and
      visible lesions were scored. Dogs were observed every 8 hours for vomiting and
      diarrhea. Median total scores for each group were compared each day of endoscopic
      examination and total dog-days of vomiting and diarrhea were compared.
      Significance was determined at P < .05. RESULTS: There were significant
      differences in total scores of the aspirin group and both the placebo and
      deracoxib groups on days 6, 14, and 28. No significant differences in total
      scores were found between placebo and deracoxib on days 6, 14, and 28.
      Significant differences in dog-days of vomiting were found between the aspirin
      and deracoxib groups whereas no significant differences were found between the
      deracoxib and placebo groups. There was no detectable effect of treatment on dog
      days of diarrhea. CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of
      deracoxib to healthy dogs resulted in significantly lower gastric lesion scores,
      and fewer days of vomiting compared to aspirin, indicating that deracoxib is
      better tolerated than aspirin in some dogs.

PMID- 17186841
TI  - Comparison of pharmacodynamic and pharmacokinetic indices of efficacy for 5
      fluoroquinolones toward pathogens of dogs and cats.
AB  - BACKGROUND: Fluoroquinolones are often used interchangeably in dogs and cats.
      HYPOTHESIS: Predicted therapeutic efficacy differs among fluoroquinolones.
      ANIMALS: Bacterial pathogens isolated from dogs and cats. METHODS: Using
      microtube-dilution procedures, percent resistance and 2
      pharmacodynamic/pharmacokinetic indices (maximum concentration/minimum inhibitory
      concentration [Cmax/MIC] [target 0.10] and area under curve/minimum inhibitory
      concentration [AUC/MIC] [target 0.125]) were compared prospectively at low and
      high doses (mg/kg) for ciprofloxacin (5 and 20), difloxacin (5 and 10),
      enrofloxacin (including enrofloxacin+ciprofloxacin) (5 and 20), marbofloxacin
      (2.5 and 5), and orbifloxacin (2.5 and 7.5). Indices were calculated for
      organisms represented by < or = 15 isolates. RESULTS: Percent resistance for all
      Gram-negative (n = 180; 20+/-3%; 39+/-5% for Escherichia coli) and Gram-positive
      isolates (n = 66; 18+/-3%) did not differ among drugs or organisms. The pattern
      of Cmax/MIC was generally enrofloxacin+ciprofloxacin > or = enrofloxacin or
      ciprofloxacin > or = marbofloxacin > or = orbifloxacin > or = difloxacin; and for
      AUIC/ MIC, enrofloxacin+ciprofloxacin > or = marbofloxacin > or = ciprofloxacin >
      or = enrofloxacin > difloxacin > orbifloxacin. Among susceptible Gram-negative
      isolates studied (n = 117), targeted Cmax/MIC or AUC/MIC were achieved in 88% of
      E. coli, 53% of Proteus mirabilis, and 35% of Pseudomonas aeruginosa; and for
      susceptible Gram-positive isolates studied (n = 49), 53% of Streptotoccus spp.
      and Staphylococcus intermedius and 27% of Staphylococcus spp. At the high dose,
      the proportion of isolates for which a target was reached was: ciprofloxacin,
      enrofloxacin+ciprofloaxin, and marbofloxacin (77%), enrofloxacin (73%),
      orbifloxacin (51%), and difloxacin (40%); and at the low dose,
      enrofloxacin+ciprofloxacin and enrofloxacin (43%), ciprofloxacin (40%),
      marbofloxacin (39%), orbifloxacin (29%), and difloxacin (28%). CONCLUSIONS: E.
      coli resistance to fluoroquinolones approximated 40%. For susceptible isolates,
      enrofloxacin, marbofloxacin, and ciprofloxacin more consistently reached indices
      associated with predicted efficacy, but only at the high dose.

PMID- 17186842
TI  - Comparison of the effects of daily and intermittent-dose calcitriol on serum
      parathyroid hormone and ionized calcium concentrations in normal cats and cats
      with chronic renal failure.
AB  - BACKGROUND: Chronic renal failure is complicated by secondary
      hyperparathyroidism, which traditionally has been controlled by dietary
      restriction of phosphorus and administration of phosphorus binders. Early
      treatment of patients with chronic renal failure with calcitriol may be indicated
      because once established, parathyroid gland hyperplasia does not readily resolve
      with therapy. HYPOTHESIS: Daily and intermittent dosing of calcitriol will
      decrease plasma parathyroid hormone concentration in normal cats and cats with
      chronic renal failure without causing ionized hypercalcemia. ANIMALS: Ten normal
      cats; 10 cats with chronic renal failure. METHODS: Phase 1 was daily calcitriol
      administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent
      calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout
      period separated phases 1 and 2. Before each phase, calcitriol, parathyroid
      hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of
      both phases, serum ionized calcium concentrations were measured. On the last day
      of both phases, calcitriol, parathyroid hormone, and ionized calcium
      concentrations were measured 0, 2, 4, and 6 hours after calcitriol
      administration. RESULTS: Overall, serum parathyroid hormone concentrations were
      significantly higher in cats with chronic renal failure than in normal cats (P =
      .022), but serum parathyroid hormone concentrations for both normal cats and cats
      with chronic renal failure were not significantly different before and after 14
      days of treatment with calcitriol, regardless of whether calcitriol was
      administered daily or intermittently. Adverse effects of calcitriol
      administration (specifically ionized hypercalcemia) were not seen in either
      feline group during either phase of the study over the 3-day evaluation after
      calcitriol administration was initiated. CONCLUSIONS AND CLINICAL IMPORTANCE: At
      the dosages used, calcitriol treatment did not result in significant differences
      in serum parathyroid hormone concentrations before and after treatment in both
      normal cats and cats with chronic renal failure. With these dosages, adverse
      affects of calcitriol administration were not seen. Potential reasons for lack of
      apparent effect include small sample size, insufficient duration of study,
      insufficient dosage of calcitriol, problems with formulation or administration of
      calcitriol, and variable gastrointestinal absorption of calcitriol.

PMID- 17186843
TI  - Esophageal dysmotility in young dogs.
AB  - BACKGROUND: Abnormal esophageal motility can exist without megaesophagus,
      although its prevalence in dogs is unknown and its cause has not been elucidated.
      HYPOTHESIS: Esophageal dysmotility without overt megaesophagus exists in both
      symptomatic and asymptomatic young dogs, and motility can improve with age.
      ANIMALS: Dogs examined at the Department of Veterinary Medicine, University of
      Cambridge for regurgitation, but without evidence of megaesophagus on
      radiographs, and a further group of asymptomatic dogs. METHODS: Dogs underwent an
      initial and a repeat videofluoroscopic swallowing study. Images were reviewed and
      5 criteria of esophageal motility evaluated. RESULTS: Eight affected dogs were
      identified (median age 9 months), and terrier dogs predominated (6 terriers of 3
      breeds). Esophageal motility was reduced either globally (n = 3) or segmentally
      (n = 5). Repeat examination at a median of 3 months revealed that regurgitation
      had reduced or resolved in the majority of terrier dogs, and 4 of 6 cases
      demonstrated an improvement in esophageal motility. Videofluoroscopic evaluation
      of young (median age 11 months) asymptomatic dogs of various breeds (n = 22)
      revealed evidence of esophageal dysmotility in 4 of 5 control terrier dogs.
      Repeat evaluation demonstrated an improvement in esophageal motility in 3 dogs.
      CONCLUSION AND CLINICAL IMPORTANCE: Esophageal dysmotility without overt
      megaesophagus occurs in young terrier dogs, and affected animals can be
      symptomatic or asymptomatic. Further, an improvement in esophageal motility
      occurs with time in some dogs, and might represent a syndrome of delayed
      esophageal maturation.

PMID- 17186844
TI  - Coagulation profiles in dogs with congenital portosystemic shunts before and
      after surgical attenuation.
AB  - BACKGROUND: Serious postoperative hemorrhage has been reported in dogs after
      closure of congenital portosystemic shunts (CPS). HYPOTHESIS: In dogs with
      portosystemic shunting, low coagulation factor activity is responsible for
      coagulopathy, which can cause complications after surgery. ANIMALS: Thirty-four
      dogs with CPS and 39 healthy dogs. METHODS: In a prospective study, coagulation
      times, platelet count, and the activity of 8 coagulation factors were measured in
      dogs before and after surgical shunt attenuation and in 31 healthy dogs. The
      effect of abdominal surgery on hemostasis was determined at ovariectomy in 8
      healthy dogs. RESULTS: Dogs with CPS had lower platelet counts, lower activity of
      factors II, V, VII, and X, and increased factor VIII and activated partial
      thromboplastin time (APTT) compared to healthy dogs. After surgical attenuation,
      dogs with CPS had decreased platelet counts and activity of factors I, II, V,
      VII, IX, X, and XI and a prolonged prothrombin time (PT). Ovariectomy resulted in
      decreased activity of factors VII and X. Six weeks after surgery, portosystemic
      shunting persisted in 9 of 30 dogs, with no improvement of hemostatic values. CPS
      dogs without shunting had improved coagulation times and increased activity of
      factors II, V, VII, and X. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with CPS
      have lower activity of clotting factors compared to healthy dogs, resulting in a
      prolonged APTT. Surgical attenuation of the shunt results in increased
      abnormalities in coagulation times and factors immediately after surgery.
      Hemostasis is normalized after complete recovery of shunting after attenuation,
      in contrast to dogs with persistent shunting.

PMID- 17186845
TI  - High complication rate of an automatic Tru-Cut biopsy gun device for liver biopsy
      in cats.
AB  - BACKGROUND: Liver biopsies taken with an automatic Tru-Cut biopsy gun device
      caused unexpected fatal shock reactions in cats. The goal of the present study
      was to determine if this biopsy device caused more frequent fatal complications
      than did a semiautomatic device. ANIMALS: All cats referred to the Utrecht
      University, between October 1, 2002, and October 31, 2004, in which ultrasound
      guided Tru-Cut liver biopsies were taken. The indications for liver biopsy were
      increased liver enzyme activity, increased bile acid concentrations,
      ultrasonographic abnormalities of the liver, ultrasonographic abnormalities of
      the bile ducts, or some combination of these findings. Coagulation parameters
      were normal. METHODS: From October 1, 2002, until October 31, 2003, 26 cats were
      biopsied with an automatic biopsy device. Between November 1, 2003, and October
      31, 2004, 19 cats underwent liver biopsy with a semiautomatic biopsy device.
      RESULTS: In the first period. 5 of the 26 cats (19%) developed severe shock
      within 15 minutes. Resuscitation was not successful. In the second period, none
      of the 19 cats experienced any major adverse effect. There were no significant
      differences between the 2 groups with respect to diagnosis, clinical signs,
      clinicopathologic findings, or the use of anesthetics. CONCLUSIONS AND CLINICAL
      IMPORTANCE: We conclude that the difference in complication rate is explained by
      the biopsy technique used. The pressure wave, which occurs when firing the
      automatic device, may have caused intense vagotonia and shock. Use of this
      automatic biopsy device should be avoided in cats because of the high risk of
      fatal complications.

PMID- 17186846
TI  - Disseminated intravascular coagulation in cats.
AB  - The purpose of this study was to describe the clinical characteristics of cats
      with disseminated intravascular coagulation (DIC), including associated diseases
      and hemostatic abnormalities, and to identify risk factors for death and
      treatments that potentially altered outcome. Medical records for cats with DIC
      from 1990-2004 were evaluated retrospectively. Inclusion criteria were the
      presence of an underlying disorder associated with DIC and either postmortem
      examination findings of intravascular fibrin deposition or thrombosis, or both of
      2 or more organs or coagulation profiles that meet 3 of 5 criteria: prolonged
      prothrombin time (PT), activated partial thromboplastin time (aPTT), presence of
      fibrin degradation products (FDP), low plasma fibrinogen (FIB) concentration, and
      thrombocytopenia (<160,000 platelets/microL). Signalment, historical data,
      clinical findings, clinicopathologic data, underlying disorders, management, and
      outcome were recorded. Forty-six cats fulfilled the criteria for DIC. Cats ranged
      in age from 7 weeks to 17 years (median, 9 years). Hemorrhage was noted in 7 of
      46 cats (15%). Three of 46 cats (7%) survived, whereas 43 of 46 (93%) died or
      were euthanized. The most common underlying disorders were lymphoma, other forms
      of neoplasia, pancreatitis, and sepsis. There was no association detected between
      outcome and signalment; underlying disease; hemorrhage; abnormalities in aPTT,
      FIB, FDPs, platelet count; transfusion of blood products; and heparin therapy.
      However, the median PT of nonsurvivors was more prolonged than in survivors (P <
      .005). DIC in cats can result from a variety of neoplastic, infectious, and
      inflammatory disorders, and is associated with a high case fatality rate.

PMID- 17186847
TI  - Investigation of physiologic leukopenia in Belgian Tervuren dogs.
AB  - BACKGROUND: Physiologic leukopenia in Tervuren dogs was reported in North America
      with a higher frequency in aged Tervurens. If not recognized, physiologic
      leukopenia can provoke unnecessary clinical investigations. HYPOTHESIS: The
      primary objective was to compare Tervurens and control dogs in Belgium with
      respect to the numbers of dogs with physiologic leukopenia. The secondary
      objectives were to compare Tervurens with control dogs and age classes within
      Tervurens and controls for parameters related to physiologic leukopenia. ANIMALS:
      Tervurens (n = 94) and control dogs (n = 48, maximum of 5 dogs per breed and 5
      mixed breed dogs) were entered into the study. Dogs were 1-11 years old and
      healthy on routine physical examination. Dogs had no history of disease or drug
      administration in the previous 2 months. METHODS: Hematologic analyses were
      performed by an automated device within 30 hours of sampling. Blood smears were
      evaluated for cellular morphologic anomalies. RESULTS: Only 1 of the 94 Tervuren
      dogs had physiologic leukopenia (1.06%; 95% confidence interval, 0.05-5.22).
      Furthermore, the white blood cell (WBC) count in Tervuren dogs (median, 10.00 x
      109/L; range, 5.90-20.80) was not significantly different (P = .55) from that of
      control dogs (median, 9.75 x 109/L; range, 5.20-20.90). The WBC count decreased
      significantly (P < .001) with age in Tervuren dogs. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Physiologic leukopenia is uncommon in the Belgian Tervuren dog.
      Differences with earlier data published in North America might be due to genetic
      or environmental differences.

PMID- 17186848
TI  - Clinical and echocardiographic features of primary infundibular stenosis with
      intact ventricular septum in dogs.
AB  - BACKGROUND: Primary infundibular stenosis is a rare congenital defect in which
      the right ventricle is divided into a proximal "high-pressure" chamber and a
      distal "low-pressure" chamber. The condition can be misdiagnosed as ventricular
      septal defect or valvular pulmonic stenosis and the disease severity
      underestimated. The purpose of this study was to provide a detailed clinical and
      echocardiographic description of this anomaly in a series of dogs. HYPOTHESIS:
      Several anatomic forms of infundibular stenosis exist. High resolution two
      dimensional echocardiography could differentiate 3 gross anatomic substrates.
      Knowledge of the anatomy of the obstructing lesion could influence options for
      corrective interventions. ANIMALS: Thirteen dogs examined at the Ontario
      Veterinary College teaching hospital from 1994 to 2005 with an ultrasound
      diagnosis of subpulmonic stenasis. METHODS: A retrospective review was made of
      case records from 1994 to 2005. RESULTS: Thirteen dogs were identified as having
      primary infundibular stenosis, with apparent increased prevalence in Golden
      Retrievers (8/13, 62%) and Siberian Huskies (3/13, 23%). Three types of
      infundibular lesions were identified by ultrasound in 11/13 dogs: a fibrous
      diaphragm (6), fibromuscular (4), and muscular obstruction (1). Two dogs with a
      fibrous diaphragm underwent direct surgical dilation without the use of
      cardiopulmonary bypass or inflow occlusion, resulting in substantial reduction of
      the severity of stenosis. CONCLUSION AND CLINICAL IMPORTANCE: Accurate
      determination of the severity of the stenosis and the anatomy of the obstructing
      lesion are important in devising a treatment strategy. Recognition of the fibrous
      diaphragm by echocardiography identifies a subset of dogs potentially amenable to
      surgical dilation without the need for cardiopulmonary bypass.

PMID- 17186849
TI  - Cardiovascular involvement in 8 dogs with blastomyces dermatitidis infection.
AB  - BACKGROUND: Blastomycosis is a common systemic fungal infection in dogs.
      HYPOTHESIS: Dogs with cardiovascular involvement may have abnormalities in
      electrical conduction and valvular function, and may have a worse prognosis.
      ANIMALS: Eight client-owned animals. METHODS: Dogs with cardiovascular lesions
      caused by blastomycosis were identified from retrospective evaluation of medical
      records. RESULTS: Five dogs had de novo infections and 3 had recurrences of
      previously treated infections. Harsh labored breathing, lethargy, and anorexia
      were the most common historic complaints. Three dogs had syncope. Physical
      examination and clinicopathologic data were typical of blastomycosis and included
      dyspnea, increased lung sounds, and lethargy. In addition, 3 dogs had heart
      murmurs and 1 had a third-degree atrioventricular block. Four dogs had
      myocarditis and 2 had pericarditis or epicarditis. Two dogs had cardiac signs
      attributed to extracardiac compression by fungal granulomas and clinical signs
      were relieved by treatment. Half of the remaining 6 dogs were euthanized; 2 of
      these were not treated. Of the remaining 3 dogs, 1 dog died acutely while
      sleeping; the second died intraoperatively during an attempt to place an
      epicardial pacemaker; and the third had Blastomyces-induced endocarditis and died
      of heart failure. CONCLUSIONS AND CLINICAL IMPORTANCE: Blastomycosis should be
      considered in the differential diagnosis of dogs from endemic areas with
      inflammatory myocarditis, heart block, heart base or intracardiac mass lesions,
      syncope, or endocarditis.

PMID- 17186850
TI  - Prevalence of unilateral and bilateral deafness in border collies and association
      with phenotype.
AB  - BACKGROUND: Congenital sensorineural deafness (CSD) occurs in Border Collies, but
      its prevalence and inheritance are unknown. This study estimated the prevalence
      of CSD in Border Collies and investigated its association with phenotypic
      attributes linked to the merle gene, including coat pigmentation and iris color.
      HYPOTHESIS: Deafness in Border Collies is associated with pigmentation patterns
      linked to the merle gene. ANIMALS: A total of 2597 Border Collies from the United
      Kingdom. METHODS: A retrospective study of Border Collies tested, during 1994
      2002, by using brainstem auditory evoked responses. Associations between deafness
      and phenotypic attributes were assessed by using generalized logistic regression.
      RESULTS: The prevalence of CSD in puppies was estimated as 2.8%. The
      corresponding rates of unilateral and bilateral CSD were 2.3 and 0.5%,
      respectively. Adjustment for clustering of hearing status by litter reduced the
      overall prevalence estimate to 1.6%. There was no association between CSD and sex
      (P = .2). Deaf Border Collies had higher rates of merle coat pigmentation, blue
      iris pigment, and excess white on the head than normal hearing Border Collies
      (all P < .001). The odds of deafness were increased by a factor of 14 for Border
      Collies with deaf dams, relative to the odds for dogs with normal dams (P =
      .007), after adjustment for phenotypic attributes. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Associations between CSD and pigmentation patterns linked to the
      merle gene were demonstrated for Border Collies. Evidence for an inherited
      component to CSD in Border Collies supports selective breeding from only tested
      and normal parents to reduce the prevalence of this disease.

PMID- 17186851
TI  - Hypothyroid-associated central vestibular disease in 10 dogs: 1999-2005.
AB  - BACKGROUND: With the exception of myxedema coma, central nervous system signs are
      rare in hypothyroid dogs. HYPOTHESIS: Central vestibular dysfunction is a
      possible and reversible manifestation of hypothyroidism. ANIMALS: Medical records
      of dogs with vestibular dysfunction and hypothyroidism were reviewed. Of 113
      records identified, 10 dogs with at least 2 concurrent clinical neurologic
      abnormalities localizable to the central vestibular system were included.
      METHODS: Retrospective, descriptive study. RESULTS: Median age at diagnosis was 7
      years (range, 5-10 years). All dogs were referred for progressive neurologic
      disease. Lesions were localized to the myelencephalic region in 5 dogs and to the
      vestibulocerebellum in 5 dogs. Two dogs had evidence of multifocal intracranial
      disease. Non-neurologic physical abnormalities suggestive of hypothyroidism were
      absent in 7 of 10 dogs. Hypercholesterolemia was the only consistent
      clinicopathologic abnormality detected, and was present in 7 of 10 dogs. All dogs
      had total thyroxine (TT4) and free thyroxine (fT4) concentrations below reference
      ranges, and 9 of 10 had increased TSH concentrations. Intracranial imaging
      studies were normal in 5 of 8 dogs, and identified lesions consistent with
      infarctions in 3 of 8 dogs. Albuminocytologic dissociation was detected in 5 of 6
      CSF analyses. Brainstem auditory-evoked responses disclosed prolonged wave V
      latencies in 3 of 4 dogs tested. No other causes of central vestibular
      dysfunction were identified during other diagnostic investigations. The median
      time from initiation of treatment to clinical improvement was 4 days. Vestibular
      signs resolved in 9 of 10 dogs within 4 weeks. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Although the pathogenesis in dogs without evidence of infarction is
      unknown, central vestibular dysfunction appears to be a rare but reversible
      neurologic sequelae of hypothyroidism.

PMID- 17186852
TI  - Phase I and pharmacokinetic evaluation of the combination of orally administered
      docetaxel and cyclosporin A in tumor-bearing cats.
AB  - Intravenously administered docetaxel (DT) is problematic in cats because of the
      requirement for premedication to ameliorate acute vehicle-induced
      hypersensitivity reactions. Previously we have revealed that therapeutic plasma
      concentrations of DT can be achieved in normal and tumor-bearing dogs when DT is
      administered PO in combination with oral cyclosporin A (CSA). The purpose of this
      study was to identify the maximally tolerated dosage and characterize the
      pharmacokinetic disposition of oral DT combined with CSA in cats with tumors.
      Eighteen tumor-bearing cats were enrolled in this phase I dose escalation and
      pharmacokinetic study. DT was administered by gavage with CSA (5 mg/kg) twice
      over a 3-week period. The starting dose of DT was 1.0 mg/kg. Based on the
      clinical toxicity profile, with gastrointestinal adverse effects and hematologic
      toxicity the maximal tolerated dose of oral DT was 1.75 mg/kg in combination with
      5 mg/kg CSA. Additional studies are necessary to determine the efficacy of DT/CSA
      in cats with epithelial tumors.

PMID- 17186853
TI  - Myeloma-related disorders in cats commonly present as extramedullary neoplasms in
      contrast to myeloma in human patients: 24 cases with clinical follow-up.
AB  - BACKGROUND: Myeloma-related disorders (MRD) are rare neoplasms of plasma cells.
      Published case reports describe a diversity of clinical presentations with
      confusing terminology and diagnostic criteria as a consequence of the assumption
      that MRD in cats are analogous to those in dogs or humans. OBJECTIVE: The aim of
      the study was to describe clinical, clinicopathologic and imaging findings,
      response to treatment, survival and possible associations with other diseases or
      vaccination in a large case series. A priori hypotheses were that cats with MRD
      commonly present with extramedullary involvement and uncommonly have radiographic
      bone lesions, in contrast to human patients. ANIMALS: Twenty-four cats with MRD
      confirmed by cytology or histopathology and immunohistochemistry. METHOD: A
      multicenter retrospective study was performed. RESULTS: Two types of clinical
      presentation were observed. The first group (n = 17) had neoplasia involving
      abdominal organs, bone marrow, or both. All developed systemic clinical signs and
      paraproteinemia. Five of 7 cats that received chemotherapy improved clinically or
      had decreased serum globulin concentration (median survival, 12.3 months; range,
      8.5-22 months). The second group comprised 7 cats with skin masses, 2 of which
      were paraproteinemic and developed rapidly worsening systemic signs. In cats
      without systemic signs, excision of the skin masses appeared to be associated
      with prolonged survival (up to 2.4 years). Cats with MRD commonly presented with
      extramedullary involvement (67%), versus humans with MRD (5%) (P < .001), and
      uncommonly presented with radiographic bone lesions (8%) versus humans with MRD
      (80%) (P < .001). CONCLUSIONS: Radiographic bone lesions are uncommon in cats
      with MRD and extramedullary presentation is common, relative to human myeloma.

PMID- 17186854
TI  - Single agent gemcitabine chemotherapy in dogs with spontaneously occurring
      lymphoma.
AB  - BACKGROUND: Gemcitabine has been shown to be effective as a single agent in a
      variety of tumors including nonHodgkin's lymphoma. Its use in veterinary medicine
      has been limited and to date this drug has not been used as a first-line therapy
      in dogs with lymphoma. HYPOTHESIS: Gemcitabine as a single agent may be
      efficacious in dogs presented for the first time with lymphoma. ANIMALS: Twenty
      four dogs with spontaneously occurring lymphoma. METHODS: All dogs were
      clinically staged and given gemcitabine at 400 mg/m(2) over a 30-minute
      intravenous infusion weekly for 3 weeks and then given 1 week off treatment
      before starting a second cycle. RESULTS: A single dose of gemcitabine lowered
      both neutrophil count (decrease in mean neutrophil count from 10,640 cells/
      microL to 3,140 cells/microL) and platelet count (decrease in mean platelet count
      from 201,290 cells/microL to 139,190 cells/microL) 7 days after administration.
      Consequently gemcitabine dosage was reduced at the second treatment in 8 of 21
      dogs or a dose delay of 1-7 days and a reduction of dosage was used in 7 of 21
      dogs. Seven dogs completed the assigned 4-week cycle. Two of these dogs had
      progressive disease and 5 had stable disease. No objective responses were seen in
      dogs treated with a second cycle of gemcitabine. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Gemcitabine administration as a single agent resulted in hematologic
      toxicity and did not reduce lymphoma burden. If gemcitabine is to be used in
      veterinary medicine, additional prospective pharmacologic studies should be done
      to determine the appropriate dosage, regimen, and schedule of use before it can
      be recommended for use in the treatment of dogs with lymphoma as a single agent.

PMID- 17186855
TI  - Response of canine cutaneous epitheliotropic lymphoma to lomustine (CCNU): a
      retrospective study of 46 cases (1999-2004).
AB  - BACKGROUND: Epitheliotropic lymphoma (ELSA) is an uncommon cutaneous canine
      malignancy of T lymphocytes. A consensus regarding the therapeutic standard of
      care is lacking, warranting evaluation of chemotherapeutic agents traditionally
      employed against canine nodal lymphoma in the treatment of ELSA. HYPOTHESIS: The
      purpose of this retrospective, multi-institutional study was to evaluate the
      efficacy of 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) in the treatment
      of ELSA. ANIMALS: Forty-six dogs with adequate follow-up and treatment response
      information. METHODS: All cases were diagnosed histopathologically.
      Immunohistochemisty (CD3, CD79a) was performed on 42/46 samples. RESULTS:
      Presenting skin lesions included generalized scales (25/46), plaques or nodules
      (22/46), mucocutaneous lesions (14/ 46), and corneal involvement (1/46). Lymph
      node involvement and Sezary syndrome were documented in 7 and 2 dogs,
      respectively. The median number of CCNU treatments was 4 (range, 1-11), with a
      median starting dose of 60 mg/m(2) (range, 30-95). Of the 46 dogs, 15 achieved
      complete remission, 23 achieved partial remission, 5 had stable disease, and 3
      had progressive disease, for an overall response rate of 83%. The median number
      of treatments to achieve a response was 1 (range, 1-6). The overall median
      duration of response was 94 days (range, 22-282). Sixteen dose reductions were
      required because of neutropenia (10/46), thrombocytopenia (1/46), anemia (1/46),
      increased liver enzyme activity (3/46), or unspecified reasons (1/46).
      CONCLUSIONS AND CLINICAL IMPLICATIONS: Given the high response rate and well
      tolerated protocol, prospective studies are warranted to investigate the utility
      of CCNU alone or in multi-agent protocols for the treatment of ELSA.

PMID- 17186856
TI  - Hematologic changes associated with half-body irradiation in dogs with lymphoma.
AB  - BACKGROUND: Reports describe the technique and efficacy of half-body irradiation
      (HBI) of dogs with lymphoma, but few describe the distinctive toxicoses
      associated with the combination of HBI and chemotherapy. HYPOTHESIS: HBI would
      transiently affect myelocytic and erythroid variables as assessed by serial
      analysis of complete blood counts. ANIMALS: Twenty-nine dogs with lymphoma
      treated with HBI during 2002 and 2003. METHODS: A retrospective study of medical
      records of 29 dogs was performed. Two HBI protocols were used, resulting in
      delivery of either 6 Gy or 8 Gy to each half of the body, 1 month apart. Dogs
      received chemotherapy before, during, or after irradiation, or at multiple times.
      Serial hematology was available for all dogs. Data were analyzed between
      collection periods by analysis of variance (ANOVA) RESULTS: The mean granulocyte
      count significantly (P < .01) decreased from 10,017 cells/microL (data range
      3,001-20,170 cells/ microL) before the first radiation treatment to 3,250
      cells/microL (820-4,400 cells/microL) at week 5 (P < .01). Three weeks after this
      nadir, the mean increased to 10,150 cells/microL (900-26,700 cells/microL). The
      hematocrit did not change (36-38%). Thrombocytopenia (<100,000/microL) occurred
      in 10 dogs. Two dogs died because of complications associated with
      thrombocytopenia. No significant difference in toxicity was found between the 6
      Gy and 8 Gy group. CONCLUSIONS AND CLINICAL IMPORTANCE: HBI was myelosuppressive
      but effects were short term and resolved in 22 of 24 dogs. Further studies are
      needed to elucidate the safety and role of HBI in the treatment of dogs with
      lymphoma.

PMID- 17186857
TI  - Lung surfactant function and composition in neonatal foals and adult horses.
AB  - BACKGROUND: Lung surfactant function and composition are varied and adapted to
      the specific respiratory physiology of all mammalian species. HYPOTHESIS: Lung
      surfactant function and composition are different in neonatal foals as compared
      to adult horses. ANIMALS: Six adult horses, 7 term foals (<24 hours old), and 4
      premature foals were used. Animals were part of the Auburn University teaching
      herd except for 3 client-owned premature foals. METHODS: Bronchoalveolar lavage
      fluid (BALF) was obtained from all animals. Ultracentrifugation of cell-free BALF
      separated surfactant into crude surfactant pellets (CSP) and supernatant. Both
      fractions were analyzed for phospholipid and protein content with the Bartlett
      and bicinchoninic acid method, respectively. Phospholipid composition of the CSP
      was determined by using high-performance liquid chromatography with an
      evaporative light scatter detector. Surface tension of the CSP was measured with
      a pulsating bubble surfactometer. Results from term foals (<24 hours old) were
      compared statistically to those from adult horses. Values of P < .05 were
      considered significant. RESULTS: BALF phospholipid content was similar between
      adult horses and term foals, but BALF protein content was significantly decreased
      in term foals. Phosphatidylglycerol was significantly decreased,
      phosphatidylinositol was significantly increased, and the minimum surface tension
      was significantly increased in the CSP from term foals compared to adult horses.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Surface tension and phospholipid composition
      of surfactant in neonatal foals are significantly different compared to adult
      horses. These changes may influence biophysical and immunologic functions of
      surfactant.

PMID- 17186858
TI  - The effects of feeding and fasting on gastrointestinal sounds in adult horses.
AB  - The effect of changes in feed intake on auscultatable gastrointestinal sounds has
      not been systematically studied. Disagreement also is present in the literature
      about variation in sounds according to the quadrant of auscultation.
      Gastrointestinal sounds were recorded over the center of the left dorsal, left
      ventral, right ventral, and right dorsal quadrants and over the middle of the
      right abdominal flank. During 24 hours (n = 4) or 48 hours (n = 5) of fasting,
      there was a reduction in the intensity of gastrointestinal sounds as assessed by
      analysis of sound recordings. There was also a reduction in the number of mixing
      like and propulsive-like sounds heard by 2 blinded observers. After refeeding,
      there was a marked increase in sound. Sound intensity varied among abdominal
      quadrants, but blinded observers did not notice significant differences in the
      number of mixing-like sounds. The left dorsal quadrant was quieter than others
      during fasting and refeeding. The right ventral quadrant appeared to be least
      affected by fasting, and sounds were louder over the right ventral and right
      middle quadrants than over the others. The blinded observers' perceptions of
      sound correlated poorly with one another and with objective measures of sound
      intensity. This experiment demonstrates the effectiveness of computerized
      analysis of abdominal sound in detecting a reduction in the intensity of
      gastrointestinal sounds during fasting and their return during refeeding. The
      left dorsal quadrant was quieter than other quadrants, likely because of its
      position over the small colon. There was considerable observer variation in the
      number of intestinal sounds heard.

PMID- 17186859
TI  - Fall panicum (Panicum dichotomiflorum) hepatotoxicosis in horses and sheep.
AB  - BACKGROUND: Fourteen horses at a boarding stable in Virginia were diagnosed with
      hepatic disease and locally grown hay was implicated as the cause. HYPOTHESIS:
      Panicum dichotomiflorum, the predominant grass species in the hay, is hepatotoxic
      to horses. ANIMALS: Naturally occurring cases were adult horses of various
      breeds. Two healthy adult horses and 2 healthy adult sheep were used in feeding
      trials. METHODS: Blood and liver specimens collected from affected animals during
      the outbreak were analyzed. Some of the affected animals were treated
      supportively; the main intervention was hay withdrawal. Feeding trials were not
      blinded and no treatments were provided. Blood and liver specimens were collected
      and analyzed throughout the trials. RESULTS: Five affected animals were
      euthanized, whereas the others recovered. One research horse was euthanized for
      postmortem examination, and the other research animals recovered after hay
      withdrawal. All affected animals had evidence of hepatic disease with abnormally
      high aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), gamma
      glutamyl transferase (GGT), and alkaline phosphatase (ALP) activity. Evaluation
      of liver biopsy specimens disclosed mild lymphocytic and histiocytic
      inflammation, mild vacuolar change (hydropic degeneration), prominently clumped
      chromatin, and necrosis of individual hepatocytes. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Severe hepatotoxicosis developed rapidly after Panicum hay exposure.
      Patchy hepatocyte necrosis was observed, implicating apoptosis as the mechanism
      of hepatotoxicosis. Absence of fibrosis in the research animals indicates that
      immediate withdrawal of Panicum hay should allow all but severely affected
      animals to recover from acute exposure.

PMID- 17186861
TI  - Intestinal neoplasia in horses.
AB  - BACKGROUND: Intestinal neoplasia of horses is inadequately described. HYPOTHESIS:
      Intestinal neoplasia of horses has characteristic clinicopathologic features.
      ANIMALS: Thirty-four horses with intestinal neoplasia. METHODS: Retrospective
      study. RESULTS: Anamnesis, clinical signs, clinicopathologic and pathologic
      findings in 34 adult horses diagnosed histologically with intestinal neoplasia
      were reviewed. The horses ranged in age from 2 to 30 years (mean 16.6 years at
      presentation). The Arabian breed was most represented and there was no sex
      predisposition. The most common presenting complaints were weight loss, colic,
      anorexia, and fever. The most consistent clinical signs were poor body condition,
      tachycardia, tachypnea, fever, and diarrhea. Useful diagnostic tools included
      rectal examination, routine blood analyses, abdominocentesis, ultrasonographic
      examination, rectal biopsy, and exploratory laparotomy. Alimentary lymphoma was
      the most common intestinal neoplasia identified, followed by adenocarcinoma and
      smooth muscle tumors. The small intestine was the most common segment of
      intestine affected for all neoplasms. Intestinal neoplasia was diagnosed
      antemortem in 13 of 34 (38%) horses. The median time from onset of clinical signs
      to death or euthanasia was 1.9 months. The discharge rate was 15%. Although the
      longest survival was observed in horses with jejunal adenocarcinoma, all horses
      were eventually euthanized because of intestinal neoplasia. CONCLUSIONS: Arabian
      horses were 4.5 times more likely to have intestinal neoplasia diagnosed than
      were other breeds.

PMID- 17186860
TI  - Cardiovascular and pulmonary effects of hetastarch plus hypertonic saline
      solutions during experimental endotoxemia in anesthetized horses.
AB  - BACKGROUND: Small volume resuscitation has been advocated as a beneficial therapy
      for endotoxemia in horses but this therapy has not been investigated in a
      prospective manner. The objective of this study was to determine the
      cardiopulmonary effects of small-volume resuscitation using hypertonic saline
      solution (HSS) plus Hetastarch (HES) during experimental endotoxemia in
      anesthetized horses. HYPOTHESIS: Treatment of horses with induced endotoxemia
      using HES-HSS does not alter the response of various cardiopulmonary indices when
      compared to treatment with either small- or large-volume isotonic crystalloid
      solutions. ANIMALS: Eighteen healthy horses were randomly assigned to 1 of 3
      groups. Anesthesia was maintained with halothane. Endotoxemia was induced by
      administering 50 microg/kg of Escherichia coli endotoxin IV. The horses were
      treated over 30 minutes with 15 mL/kg of balanced polyionic crystalloid solution
      (control), 60 mL/kg of balanced polyionic crystalloid solution (ISO), or 5 mL/kg
      of HSS followed by 10 mL/kg of HES (HSS-HES). METHODS: Prospective randomized
      trial. RESULTS: Cardiac output (CO) after endotoxin infusion increased
      significantly (P < .05) from baseline in all groups, whereas mean central venous
      pressure increased significantly (P < .05) in the ISO group only. Mean pulmonary
      artery pressure increased from baseline (P < .05) in horses treated with isotonic
      fluids and HSS-HES. There was no effect of treatment with HSS-HES on CO, systemic
      vascular resistance (SVR), mean arterial pressure, blood lactate concentrations,
      or arterial oxygenation. CONCLUSIONS AND CLINICAL IMPORTANCE: The use of HSS-HES
      failed to ameliorate the deleterious hemodynamic responses associated with
      endotoxemia in horses. The clinical value of this treatment in horses with
      endotoxemia remains unconfirmed.

PMID- 17186862
TI  - Effects of norepinephrine and a combined norepinephrine and dobutamine infusion
      on systemic hemodynamics and indices of renal function in normotensive neonatal
      thoroughbred foals.
AB  - BACKGROUND: Norepinephrine is a potent vasopressor that increases arterial blood
      pressure but may have adverse effects on renal blood flow. The combination of
      norepinephrine and dobutamine may lead to improved renal perfusion compared to an
      infusion of norepinephrine alone. The effects of these drugs in the normotensive
      neonatal foal have not been reported. HYPOTHESIS: Norepinephrine increases
      arterial blood pressure. Adding dobutamine to a norepinephrine infusion will
      change the renal profile during the infusions without changing the arterial blood
      pressure. ANIMALS: Eight conscious Thoroughbred foals were used in this study.
      METHODS: Each foal received norepinephrine (0.1 microg/kg/min), combined
      norepinephrine (0.1 microg/kg/min) and dobutamine (5 microg/kg/min), and a
      control dose of saline in a masked, placebo-controlled study. Heart rate,
      arterial blood pressure (direct), and cardiac output (lithium dilution) were
      measured, and systemic vascular resistance, stroke volume, cardiac index, and
      stroke volume index were calculated. Urine output, creatinine clearance, and
      fractional excretion of sodium, potassium, and chloride were measured. RESULTS:
      Norepinephrine and a combined norepinephrine and dobutamine infusion increased
      arterial blood pressure and systemic vascular resistance and decreased heart rate
      and cardiac index as compared to saline. The combination resulted in higher
      arterial pressure than norepinephrine alone. There was no significant difference
      in urine output, creatinine clearance, or fractional excretion of electrolytes
      with either infusion as compared to saline. CONCLUSIONS AND CLINICAL IMPORTANCE:
      These data suggest that norepinephrine and a combined norepinephrine and
      dobutamine infusion cause unique hemodynamic effects without affecting indices of
      renal function, and this effect warrants further investigation.

PMID- 17186863
TI  - Juvenile idiopathic epilepsy in Egyptian Arabian foals: 22 cases (1985-2005).
AB  - BACKGROUND: Epilepsy is relatively uncommon in horses compared with other species
      and limited information is available. HYPOTHESIS: The objectives of the study
      were to describe the age of onset, clinical signs, clinicopathologic data,
      electroeticephalographic findings, treatment, and outcome, including long-term
      prognosis in Arabian foals with idiopathic epilepsy. ANIMALS: Twenty-two foals
      were included in the study. MATERIALS AND METHODS: Medical records from 1985 to
      2005 were reviewed. RESULTS: The age of onset of affected foals ranged from 2
      days to 6 months. Seizures were characterized by generalized tonic and clonic
      motor activity, staring, and loss of consciousness. The most common postictal
      signs were transient blindness and abnormal mental status. The interictal
      neurologic examination was otherwise normal. Clinicopathologic data and imaging
      diagnostics were normal except in 4 foals that developed complications.
      Electroencephalography revealed epileptiform activity in 9 of 13 foals. Foals
      were treated with benzodiazepines for the short-term; whereas phenobarbital was
      used over the long-term. Potassium bromide was added in 3 foals in which seizures
      were multiple, frequent, and difficult to control. The long-term prognosis was
      favorable with cessation of seizures by 1 year of age. The most common
      complication was head trauma. The most common concurrent disease was pneumonia.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Juvenile idiopathic epilepsy of Egyptian
      Arabian foals has an early clinical onset but appears to be self-limiting.
      Information obtained from this study strongly suggests a heritable condition that
      merits further investigation.

PMID- 17186865
TI  - Serum lactoferrin and immunoglobulin G concentrations in healthy or ill neonatal
      foals and healthy adult horses.
AB  - BACKGROUND: Lactoferrin is a colostral glycoprotein with antimicrobial
      properties. HYPOTHESES: (1) Serum lactoferrin and immunoglobulin G (IgG)
      concentrations are correlated and increase in healthy foals after ingestion of
      colostrum; (2) compared to healthy foals, ill foals will have lower lactoferrin
      concentrations that correlate with their IgG concentration, neutrophil count, the
      diagnosis of sepsis, and survival; and (3) plasma concentrations of lactoferrin
      will be less than serum concentrations. ANIMALS: Healthy foals (n = 16), mature
      horses (n = 10), and ill foals 1-4 days old (n = 111) that were examined for
      suspected sepsis were used for blood collection. Colostrum was obtained from 10
      healthy mares unrelated to the foals. METHODS: Blood was obtained from the
      healthy foals at birth and 1-3 days of age and from the ill foals at admission.
      Serum IgG was quantified by single radial immunodiffusion (SRID). Lactoferrin
      concentrations in colostrum and blood were determined by an enzyme-linked
      immunosorbant assay. The sepsis score, blood culture results, neutrophil counts,
      and survival were obtained on ill foals. RESULTS: The mean colostral lactoferrin
      concentration was 21.7 microg/mL. Compared to values at birth, serum IgG (18+/-2
      versus 2,921+/-245 mg/dL, SEM) and lactoferrin (249+/-39 versus 445+/-63 ng/mL,
      SEM) concentrations were significantly greater in healthy foals 1-3 days old.
      Serum lactoferrin concentration in 1-3-day-old healthy foals was not different
      from mature horses or ill foals. IgG and lactoferrin concentrations were
      significantly correlated only in healthy foals. Serum lactoferrin concentrations
      were significantly lower in ill neutropenic foals. The serum IgG concentration
      was significantly lower in ill foals as compared to healthy foals. Only serum IgG
      was significantly less in ill foals with a positive sepsis score and in
      nonsurvivors, Plasma lactoferrin concentrations were lower than serum
      concentrations, although values were significantly correlated. CLINICAL
      IMPORTANCE: Although both serum IgG and lactoferrin concentrations increase in
      healthy foals after ingestion of colostrum, only serum IgG is significantly
      correlated with the sepsis score and outcome.

PMID- 17186864
TI  - Investigation of a novel, heritable bleeding diathesis of Thoroughbred horses and
      development of a screening assay.
AB  - BACKGROUND: Bleeding in racing horses associated with exercise appears to be
      multifactorial, and clinical investigation into severe cases rarely occurs.
      Previously, we reported a severe bleeding diathesis in a Thoroughbred mare.
      Herein, we describe the cellular physiology of this defect, provide a diagnostic
      tool for identifying it, and demonstrate that the dysfunction is heritable.
      HYPOTHESIS: The subject has a heritable defect in platelet secretion that reduces
      thrombin generation in the absence of additional plasma factors and delays the
      onset of thrombin production even in the presence of these factors. ANIMALS: The
      study included 3 clinically normal Thoroughbred horses: the subject and her
      offspring. METHODS: Washed platelets were examined for their ability to (1)
      translocate phosphatidylserine to the outer leaflet of the platelet membrane as
      determined by annexin-V binding, (2) generate thrombin as assessed by the
      activity of the prothrombinase enzyme complex, and (3) bind fibrinogen and form
      aggregates as determined by flow cytometry. RESULTS: Subject and offspring
      platelets created procoagulant surfaces by translocating phosphatidylserine. The
      subject's platelets demonstrated reduced prothrombinase activity, resulting in
      decreased production of thrombin relative to control platelets. Subject and
      offspring platelets bound less fibrinogen than control platelets when stimulated
      with thrombin. CONCLUSIONS AND CLINICAL IMPORTANCE: The subject mare has a
      transmissible defect that involves reduced generation of thrombin by activated
      platelets, resulting in decreased aggregation and ineffective clotting. A flow
      cytometric assay of fibrinogen binding to washed platelets discriminates
      individuals with this platelet dysfunction and may be useful for discerning
      subclinical congenital or acquired platelet dysfunctions.

PMID- 17186866
TI  - Prognostic value of plasma L-lactate concentration measured cow-side with a
      portable clinical analyzer in Holstein dairy cattle with abomasal disorders.
AB  - BACKGROUND: L-Lactate has been used as a prognostic indicator for ill humans and
      animals. A portable analyzer that measures L-lactate could help veterinarians
      decide to proceed with correction of a displaced abomasum. HYPOTHESES: The
      likelihood of a dairy cow with a displaced abomasum remaining in the herd can be
      predicted by lactate concentration and other variables. ANIMALS: Thirty-four
      healthy early-lactation dairy cows, and 131 cows with abomasal displacements (DA)
      presented to Cornell University, Ithaca, NY. METHODS: Plasma L-lactate was
      measured using a commercial analyzer (i-STAT). A cow had a positive outcome (PO)
      if she remained in the herd 30 days after surgical correction of the displaced
      abomasum and a negative outcome (NO) if she was culled or died in that time. A
      multivariable model with physical examination and clinicopathologic variables for
      predicting NO for cows with right-sided abomasal displacements was constructed.
      RESULTS: The median plasma L-lactate was 0.54 mM/L (interquartile range, 0.42
      0.74) in healthy lactating Holstein cows. In cows with right-sided displaced
      abomasa, median plasma L-lactate concentrations were higher in cows with NO (5.88
      mM/L) versus PO (3.23 mM/L) (P = .002). In a multivariable model, which
      identified chloride, heart rate, and L-lactate as the best fitting variables for
      cows with right-sided displacements, the probability of NO increased as L-lactate
      increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma L-lactate concentration
      might be a useful predictor of productive outcomes in cows with right-sided
      abomasal disorders.

PMID- 17186867
TI  - Effect of rapid intravenous administration of 50% dextrose solution on phosphorus
      homeostasis in postparturient dairy cows.
AB  - BACKGROUND: Dextrose is commonly administered to postparturient dairy cows, which
      often have low plasma phosphorus concentration ([P]) as a result of anorexia and
      sudden onset of lactation. Intravenous (IV) dextrose administration causes
      hypophosphatemia in other species. HYPOTHESIS: Bolus administration of dextrose
      to postparturient dairy cows results in a transient decrease in plasma [P].
      ANIMALS: Six healthy postparturient dairy cows. METHODS: Using a crossover
      design, cows were administered 500 mL of 50% dextrose solution IV or a sham
      treatment. Plasma concentrations of glucose ([glucose]), immunoreactive insulin
      ([IRI]), and phosphorus were monitored for 12 hours after each treatment. Urine
      [P], [glucose], and volume and salivary [P] were also determined. RESULTS: Plasma
      [glucose], [IRI], and [P] were stable during sham treatment. Plasma [P] decreased
      rapidly after dextrose administration, dropping by 35% in 1 hour and remaining
      below baseline for 90 minutes. Salivary [P], urine [P], and urine volume per hour
      remained stable after dextrose administration, but glucose was detected in urine
      for up to 6 hours. The amount of glucose excreted in urine in 12 hours (11.9+/
      4.5 g) was less than 5% of the administered dose. Regression analysis revealed a
      stronger association between plasma [P] and [IRI] than between plasma [P] and
      [glucose], suggesting that hyperinsulinemia drove the hypophosphatemia.
      CONCLUSION AND CLINICAL IMPORTANCE: Results indicate that low plasma [P] should
      be expected in cows that have received IV dextrose within 1 hour before blood
      sampling. Caution is advised when administering dextrose solution to cows already
      at risk of hypophosphatemia.

PMID- 17186868
TI  - Treatment of Conidiobolus sp. pneumonia with itraconazole in a dog receiving
      immunosuppressive therapy.

PMID- 17186869
TI  - The use of intravenous human immunoglobulin in treatment of severe pemphigus
      foliaceus in a dog.

PMID- 17186870
TI  - Management of myasthenia gravis using cyclosporine in 2 dogs.

PMID- 17186871
TI  - Clinical, clinicopathologic, postmortem examination findings and familial history
      of 3 Arabians with lavender foal syndrome.

PMID- 17186872
TI  - Iron deficiency anemia in a neonatal foal.

PMID- 17186873
TI  - Idiopathic hemorrhagic pericardial effusion in cows.

PMID- 17186874
TI  - Bilateral lipid keratopathy and atherosclerosis in an alpaca (Lama pacos) due to
      hypercholesterolemia.

PMID- 17186875
TI  - Can this payment model work?

PMID- 17186876
TI  - Is Texas tort reform working?

PMID- 17186877
TI  - Subpoenaed? Don't panic.

PMID- 17186878
TI  - Malpractice insurance. Better news? More choices?

PMID- 17186879
TI  - What would you do? Alternative medicine.

PMID- 17186880
TI  - My epiphany.

PMID- 17186882
TI  - Wireless security: it's up to you.

PMID- 17186881
TI  - The ins and outs of wireless networking.

PMID- 17186883
TI  - Online CME. Fast, convenient, and ready for prime time.

PMID- 17186884
TI  - This is your brain on alien killer pimps of Nazi doom.

PMID- 17186885
TI  - Peeering into the future.

PMID- 17186886
TI  - Biomarkers. 'I'm pretty Optimistic'.

PMID- 17186887
TI  - Minds and magnets.

PMID- 17186888
TI  - Stem cells are where it's at.

PMID- 17186889
TI  - A six-foot lab rat.

PMID- 17186890
TI  - Old bugs learn some new tricks.

PMID- 17186891
TI  - Why heavy isn't healthy.

PMID- 17186892
TI  - Can we slow aging?

PMID- 17186893
TI  - Vitamin D in the spotlight.

PMID- 17186894
TI  - Targeting needless breast biopsies.

PMID- 17186895
TI  - Let's live healthier.

PMID- 17186896
TI  - Real food for thought.

PMID- 17186897
TI  - Award-winning integrated campaign raises awareness, fills beds for rural
      hospital.
AB  - Being a small hospital in a rural region does not mean that competing with
      metropolitan facilities is out of the question. Just ask Sumter Regional
      Hospital, a 143-bed acute-care facility located in Americus, GA, 134 miles south
      of Atlanta.

PMID- 17186898
TI  - 'Never feel alone' with Blue Cross Philadelphia. Nontraditional campaign promises
      the insurer's support during times of need.
AB  - New TV spots campaigning for Independence Blue Cross are the opposite of warm and
      fuzzy. In fact, they're isolating and almost chilling, but that's the point.
      Being sick or injured can make you feel alone, but having Blue Cross insurance
      means someone is always there with you.

PMID- 17186899
TI  - Radio advertising increases hospital call center volume by 48%.
AB  - Since the fall of 2005, call volume at University of Southern California
      University Hospital of Los Angeles' call center has increased by nearly 50%. How?
      The hospital embarked on a long-term radio campaign to promote its presence as a
      premier academic medical center and to increase patient volume.

PMID- 17186900
TI  - Hospital gains exposure through opening gala, builds on brand.
AB  - Baptist Memorial Health Care is one of the nation's largest health systems, with
      14 hospitals throughout western Tennessee and northern Mississippi. The 2,400-bed
      health system recently launched a new 151-bed tower at Baptist Memorial Hospital
      Golden Triangle in Columbus, MS, unveiling it to the community with a grand
      opening gala in July.

PMID- 17186901
TI  - Integrated campaign.
AB  - Virginia Hospital Center launched a multiintegrated advertising campaign that
      centers around topic-specific medical issues through the use of provocative
      advertisements. For example, the first ad, which launched in September, focuses
      on abdominal hysterectomies.

PMID- 17186902
TI  - Investigating the effects of reduced size on the properties of ferroelectrics.
AB  - A series of experiments has been undertaken to understand more about the
      fundamental origin of the thickness-induced permittivity collapse often observed
      in conventional thin film ferroelectric heterostructures. The various experiments
      are discussed, highlighting the eventual need to examine permittivity collapse in
      thin film single crystal material. It has been seen that dielectric collapse is
      not a direct consequence of reduced size, and neither is it a consequence of
      unavoidable physics associated with the ferroelectric-electrode boundary.
      Research on three-dimensional shape-constrained ferroelectrics, emphasizing self
      assembled structures based on nanoporous alumina templates and on FIB-milled
      single crystals, is also presented, and appears to represent an exciting area for
      ongoing research.

PMID- 17186903
TI  - A decade of piezoresponse force microscopy: progress, challenges, and
      opportunities.
AB  - Coupling between electrical and mechanical phenomena is a near-universal
      characteristic of inorganic and biological systems alike, with examples ranging
      from piezoelectricity in ferroelectric perovskites to complex, electromechanical
      couplings in electromotor proteins in cellular membranes. Understanding
      electromechanical functionality in materials such as ferroelectric nanocrystals
      and thin films, relaxor ferroelectrics, and biosystems requires probing these
      properties on the nanometer level of individual grain, domain, or protein fibril.
      In the last decade, piezoresponse force microscopy (PFM) was established as a
      powerful tool for nanoscale imaging, spectroscopy, and manipulation of
      ferroelectric materials. Here, we present principles and recent advances in PFM,
      including vector and frequency-dependent imaging of piezoelectric materials,
      briefly review applications for ferroelectric materials, discuss prospects for
      electromechanical imaging of local crystallographic and molecular orientations
      and disorder, and summarize future challenges and opportunities for PFM emerging
      in the second decade since its invention.

PMID- 17186904
TI  - Sample-tip interaction of piezoresponse force microscopy in ferroelectric
      nanostructures.
AB  - We report on qualitative and quantitative implications of the sample-tip
      interaction in piezoresponse force microscopy. Our finite-element analysis of
      adsorbate effects, sample heterogeneities, and tip asymmetries is in agreement
      with experimental observation of ferroelectric nanostructures. Qualitative
      discrepancies arise from locally asymmetric tip-sample interaction. Any
      quantitative determination of field-related material parameters as required for
      the verification of semiempirical models of the ferroelectric limit typically
      relies on an overestimated field across the sample. Our findings indicate that
      adsorbates reduce the actual field across the nanograin by roughly one order of
      magnitude.

PMID- 17186905
TI  - Advanced fabrication and characterization of epitaxial ferroelectric thin films
      and multilayers.
AB  - Understanding the behavior of ferroelectrics on the nanoscale level requires the
      production of materials of the highest quality and advanced characterization
      techniques for probing the fascinating properties of these systems with reduced
      dimensions. Here we give an overview of our recent achievements in this area,
      which includes the detailed study of the suppression of ferroelectricity in
      PbTiO3 thin films, the fabrication of PbTiO3/SrTiO3 superlattices in which
      ferroelectricity shows some surprising behavior, and finally the manipulation of
      nanoscale ferroelectric domains using the atomic force microscope which leads to
      the precise analysis of domain wall creep and roughness in Pb(Zr,Ti)O3 thin
      films.

PMID- 17186906
TI  - Dielectric investigations and theoretical calculations of size effect in lead
      titanate nanocrystals.
AB  - The dielectric properties of nanograin ferroelectric lead titanate crystals are
      presented. The PbTiO3 samples were prepared by pressing nanopowders into plates
      and were studied experimentally by dielectric permittivity measurements in a wide
      frequency and temperature range. The TC dependence obtained showed a critical
      change of behavior with increasing mean nanoparticle size in the 9-nm region. The
      theoretical calculations based on Monte Carlo simulation were performed to
      describe the behavior of this material. It was shown that the distribution of
      nanoparticle sizes in the sample taken into account with the Monte Carlo method
      describes the dielectric properties of PbTiO3 nanocrystals quite well.

PMID- 17186907
TI  - Evolution of nanodomains in the uniaxial relaxor Sr0.61Ba0.39Nb2O6:Ce.
AB  - The evolution of the nanodomain pattern of the uniaxial relaxor ferroelectric
      strontium barium niobate doped with cerium was studied by piezoresponse force
      microscopy (PFM). The fractal-like nanodomains observed at room temperature decay
      on heating. At temperatures up to about 15 K above the Curie temperature, Tc =
      320 K, areas of correlated polarization are still visible. On cooling from the
      paraelectric state to below Tc, a slow isothermal growth of nanodomain was found.
      The mean domain size increases according to a logarithmic law as predicted for
      the three-dimensional random field Ising model.

PMID- 17186908
TI  - KTa0.6Nb0.4O3 ferroelectric thin film behavior at microwave frequencies for
      tunable applications.
AB  - In this study about the relationships between structural and microwave electrical
      properties of KTa(1-x)NbxO3 (KTN) ferroelectric materials, a KTN thin film was
      deposited on different substrates to investigate how KTN growth affects the
      microwave behavior. Interdigital capacitors and stubs were made on these films
      through a simple engraving process. Microwave measurements under a static
      electric field showed the importance of the substrate on the circuit behavior
      and, notably, on the tuning factor.

PMID- 17186909
TI  - Comparative measurements of piezoelectric coefficient of PZT films by
      Berlincourt, interferometer, and vibrometer methods.
AB  - Chemical solution deposition (CSD) techniques were used to prepare lead zirconate
      (Zr) titanate (Ti) (PZT) thin films with Zr/Ti ratios of 30/70 and 52/48. Usually
      CSD processing is restricted to making crack-free, single-layer films of 70-nm
      thick, but modifications to the sol-gel process have permitted the fabrication of
      dense, crack-free, single layers up to 200 to 300 nm thick, which can be built-up
      into layers up to 3-microm thick. Thicker PZT films (> 2-microm single layer) can
      be produced by using a composite sol-gel/ceramic process. Knowledge of the
      electroactive properties of these materials is essential for modeling and design
      of novel micro-electromechanical systems (MEMS) devices, but accurate measurement
      of these properties is by no means straightforward. A novel, double-beam, common
      path laser interferometer has been developed to measure the longitudinal (d33)
      piezoelectric coefficient in films; the results were compared with the values
      obtained by Berlin-court and laser scanning vibrometer methods. It was found
      that, for thin-film samples, the d(33,f) values obtained from the Berlincourt
      method are usually larger: than those obtained from the interferometer and the
      vibrometer methods; the reasons for this are discussed.

PMID- 17186910
TI  - Ferroelectric-based electrostatic micromotors with nanometer gaps.
AB  - The design of the capacitive motors that are based on the electrostatic rolling
      of the thin metallic film on the ferroelectric surface is studied. It is shown
      that this method of energy conversion allows one to move the main stage of
      electromechanical energy conversion into the nanometer range when using the
      materials with high dielectric permeability (more than 500). The analysis of the
      distribution of the forces and field in the nanometer gap of the electrostatic
      micromotors is carried out. An experimental investigation of these micromotors is
      performed.

PMID- 17186911
TI  - Piezoelectric ultrathin lead titanate films prepared by deposition of aquo-diol
      solutions.
AB  - We report on the preparation of continuous ultrathin ferroelectric films of pure
      lead titanate by chemical solution deposition (CSD) methods. Aquo-diol solutions
      highly diluted have been used to obtain films with thickness down to
      approximately 13 nm, the lowest reported for CSD films. The formation of islands
      instead of continuous coatings, which has been reported when CSD is used to
      prepare ultrathin films, is avoided here. The piezoelectric activity of the films
      has been characterized by piezoresponse. force microscopy, showing that the
      thinnest film obtained retains a significant piezoelectric activity at the
      nanoscale, which is promising for their use as transducer elements in
      nanoelectromechanical systems (NEMS).

PMID- 17186912
TI  - Dielectric spectroscopy of nano BaTiO3 confined in MCM-41 mesoporous molecular
      sieve materials.
AB  - Dielectric properties of barium titanate (BaTiO3) particles, synthesized directly
      in the pores of MCM-41 materials, have been investigated in the frequency range
      from 20 Hz to 1 MHz for temperature intervals from 100 K to 500 K. The dielectric
      spectra of BaTiO3 confined in these molecular sieves were compared with the
      results obtained from the investigation of pure MCM-41 materials. Obtained
      results confirmed successful incorporation of BaTiO3 into porous matrix, but no
      phase transition from paraelectric to ferroelectric phase was observed due to the
      particle size being smaller than the critical size. Also, the overall dielectric
      response of investigated materials is strongly influenced by adsorbed water
      molecules.

PMID- 17186913
TI  - Higher-order electromechanical response of thin films by contact resonance
      piezoresponse force microscopy.
AB  - Piezoresponse scanning force microscopy (PFM) has turned into an established
      technique for imaging ferroelectric domains in ferroelectric thin films. At least
      for soft cantilevers, the piezoresponse signal is not only dependent on the
      elastic properties of the material under investigation but also on the elastic
      properties of the cantilever. Due to this dependency, the cantilever response
      and, therefore, the measured properties depend on the frequency of the small
      alternating current (AC) testing voltage. At the contact resonance, the
      cantilever response is maximum, and this increased sensitivity can be used to
      detect very small signals or to decrease the voltage applied to the sample. We
      have shown that by using the hysteretic ferroelectric switching, it is possible
      to separate the signal into its components (viz. electromechanical and
      electrostatic contributions). Additionally, the measurement frequency can be
      tuned such that the second and third harmonics of the electromechanical response
      can be detected at the cantilever resonance, providing information about the
      higher-order electromechanical coefficients. We assume that this nonlinear
      behavior seen in local and macroscopic measurements is rooted in the nonlinearity
      of the dielectric permittivity. Our results are of crucial importance for the
      study of ferroelectric and electromechanical properties of nanostructures.

PMID- 17186914
TI  - Paraelectric thin films by nanoscale engineering of epitaxy and planar anisotropy
      for microwave phase shifter applications.
AB  - Epitaxial and (110) oriented paraelectric thin films of Ba0.60Sro.40TiO3 were
      grown on (100) oriented NdGaO3 orthorhombic substrates, and the nonlinear
      dielectric properties were studied at 10 GHz along selected in-plane
      crystallographic directions in the film thickness range of 25-1200 nm. The
      measured dielectric properties show strong residual strain and in-plane
      directional dependence. For instance, the in-plane relative permittivity is found
      to vary from as much as 500 to 150 along [110] and [001], respectively, in the
      600 nm film. Tunability was found to vary from as much as 54% to 20% in all films
      and directions. In a given film, the best tunability is observed along the
      compressed axis in a mixed strain state, 54% along [110] in the 600 nm film. It
      is shown that, by nanoscale manipulation of epitaxy and planar anisotropy, the
      return loss and phase shift in a paraelectric can be tuned over a rather wide
      range. The approach presented herein opens avenues for obtaining various degrees
      of phase shift on the same film, enabling one with an additional degree of
      freedom in device design and fabrication as well as multifunctionality.

PMID- 17186915
TI  - Ultra-thin and isolated dots in polycrystalline lead zirconate titanate films.
AB  - Size effects with critical thickness or minimum volume for ferroelectricity are
      of importance in the application of polycrystalline PZT thin films as future
      memory devices and as storage media. Isolated dots of perovskite phases in the
      matrix of pyrochlore were synthesized by isothermal annealing through
      transformation from amorphous to perovskite. Control of the transformation
      kinetics allows us to produce the isolated ferroelectric dots with a diameter of
      50 nm. Domain structure of the isolated dots is also studied by piezoresponse
      force microscopy. As prepared, all isolated dots contain perpendicularly
      polarized monodomains. Domain structures and switching behaviors of the isolated
      dots are similar to those of the single crystalline PZT films. Polycrystalline
      PZT films with a thickness of 50 nm were also investigated. They show excellent
      piezoresponse properties and switching behaviors. Ultra-thin polycrystalline PZT
      films can play a major role in the application of future ferroelectric memories
      and field-effect transistors as well as for storage media using the local probe
      technique.

PMID- 17186916
TI  - 1-D simulation of a novel nonvolatile resistive random access memory device.
AB  - The operation of a novel, nonvolatile memory device based on a conductive
      ferroelectric/semiconductor thin film multilayer stack is simulated numerically.
      The simulation involves the self-consistent steady-state solution of the
      transport equation for electrons assuming a drift-diffusion transport mechanism
      and the Poisson equation. Special emphasis is put on the screening of the
      spontaneous polarization by conduction electrons as a function of the applied
      voltage. Depending on the orientation of the polarization in the ferroelectric
      layer, a high and a low resistive state are found, giving rise to a hysteretic I
      V characteristic. The switching ratio, ranging from > 50% to several orders of
      magnitude, is calculated as a function of the dopant content. The suggested model
      provides one possible physical explanation of the I-V hysteresis observed for
      single-layer ferroelectric devices, if interfacial layers are taken into
      consideration. The approach will allow one to develop guidelines to improve the
      performance of these devices.

PMID- 17186917
TI  - Interlayer coupling in ferroelectric bilayer and superlattice heterostructures.
AB  - Ferroelectric multilayers and superlattices have gained interest for dynamic
      random access memory (DRAM) applications and as active elements in tunable
      microwave devices in the telecommunications industry. A number of experimental
      studies have shown that these materials have many peculiar properties which
      cannot be described by a simple series connection of the individual layers that
      make up the heterostructures. A thermodynamic analysis is presented to
      demonstrate that ferroelectric multilayers interact through internal elastic,
      electrical, and electromechanical fields and the strength of the coupling can be
      quantitatively described using Landau theory of phase transformations, theory of
      elasticity, and principles of electrostatics. The theoretical analysis shows that
      compositional variations across ferroelectric bilayers result in a broken spatial
      inversion symmetry that can lead to asymmetric thermodynamic potentials favoring
      one ferroelectric ground state over the other. Furthermore, the thermodynamic
      modeling indicates that there is a strong electrostatic coupling between the
      layers that leads to the suppression of ferroelectricity at a critical
      paraelectric layer thickness for ferroelectric-paraelectric bilayers. This
      bilayer is expected to have a gigantic dielectric response similar to the
      dielectric anomaly near Curie-Weiss temperature in homogeneous ferroelectrics at
      this critical thickness.

PMID- 17186919
TI  - Characterization of dissipation factors in terms of piezoelectric equivalent
      circuit parameters.
AB  - The equivalent circuit of a piezoelectric ceramic is established composed of the
      equivalent circuit parameters derived from the complex materials coefficients.
      The equivalent circuit parameters are connected to real and imaginary parts of
      the complex materials coefficients of the piezoelectric ceramics. With respect to
      the definition of dissipation factors, the dielectric, elastic, and piezoelectric
      dissipation factors which represent the losses in the materials are thus
      expressed through the equivalent circuit parameters. In temperature and stress
      experiments, by measuring the equivalent circuit parameters during the process of
      the temperature and stress changes, three dissipation factors are computed.
      Compared with the results of other previous research, a similar increase of the
      elastic dissipation factor with stress is observed. Moreover, it is also found
      that the elastic dissipation factor reaches its saturation over a stress level of
      about 10 MPa. The responses of dissipation factors in lower temperature (-30
      degrees C to 20 degrees C) are studied.

PMID- 17186918
TI  - Flextensional ultrasonic piezoelectric micro-motor.
AB  - This paper presents the experimental design, construction, and operational
      characteristics of a new type of standing wave piezoelectric ultrasonic micro
      motor. The motor uses a composite stator, consisting of a metallic flex-tensional
      mode converter, or "cymbal", bonded to a 2-mm-square piezoelectric plate. The
      cymbal converts contour-mode vibrations of the plate into oscillations in the
      cymbal, perpendicular to the stator plane. These are further converted into
      rotational movement in a rotor pressed against the cymbal by means of an elastic
      fin friction drive to produce the required rotary actuation. The motor operates
      on a single-phase electrical supply, and direct control of the output speed and
      torque can be achieved by adjusting the amplitude and frequency of the supply
      voltage. Noncontact optical techniques were used to assess the performance of the
      developed micro-motor. The operational characteristics were developed from the
      acceleration and deceleration characteristics. No-load output speed (11 rev s(
      1)) and stall torque (27 nNm) were derived using high-speed imaging and image
      analysis. Maximum efficiency was 0.6%.

PMID- 17186920
TI  - Microwave leakage-induced frequency shifts in the primary frequency standards
      NIST-F1 and IEN-CSF1.
AB  - In atomic fountain primary frequency standards, the atoms ideally are subjected
      to microwave fields resonant with the ground-state, hyperfine splitting only
      during the two pulses of Ramsey's separated oscillatory field measurement scheme.
      As a practical matter, however, stray microwave fields can be present that shift
      the frequency of the central Ramsey fringe and, therefore, adversely affect the
      accuracy of the standard. We investigate these uncontrolled stray fields here and
      show that the frequency errors can be measured, and indeed even the location
      within the standard determined by the behavior of the measured frequency with
      respect to microwave power in the Ramsey cavity. Experimental results that agree
      with the theory are presented as well.

PMID- 17186922
TI  - Feasibility of noncontact intracardiac ultrasound ablation and imaging catheter
      for treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) affects 1% of the population and results in a cost of
      2.8 billion dollars from hospitalizations alone. Treatments that electrically
      isolate portions of the atria are clinically effective in curing AF. However,
      such minimally invasive catheter treatments face difficulties in mechanically
      positioning the catheter tip and visualizing the anatomy of the region. We
      propose a noncontact, intracardiac transducer that can ablate tissue and provide
      rudimentary imaging to guide therapy. Our design consists of a high-power, 20 mm
      by 2 mm, 128-element, transducer array placed on the side of 7-French catheter.
      The transducer will be used in imaging mode to locate the atrial wall; then, by
      focusing at that location, a lesion can be formed. Imaging of previously formed
      lesions could potentially guide placement of subsequent lesions. Successive
      rotations of the catheter will potentially enable a contiguous circular lesion to
      be created around the pulmonary vein. The challenge of intracardiac-sized
      transducers is achieving high intensities (300-5000 W/cm2) needed to raise the
      temperature of the tissue above 43 degrees C. In this paper, we demonstrate the
      feasibility of an intracardiac-sized transducer for treatment of atrial
      fibrillation. In simulations and proof-of-concept experiments, we show a 37
      degrees C temperature rise in the lesion location and demonstrate the possibility
      of lesion imaging.

PMID- 17186923
TI  - Nonlinear propagation of ultrasound through microbubble contrast agents and
      implications for imaging.
AB  - Microbubble contrast agents produce nonlinear echoes under ultrasound insonation,
      and current imaging techniques detect these nonlinear echoes to generate contrast
      agent images accordingly. For these techniques, there is a potential problem in
      that bubbles along the ultrasound transmission path between transducer and target
      can alter the ultrasound transmission nonlinearly and contribute to the nonlinear
      echoes. This can lead to imaging artefacts, especially in regions at depth. In
      this paper we provide insight, through both simulation and experimental
      measurement, into the nonlinear propagation caused by microbubbles and the
      implications for current imaging techniques. A series of investigations at
      frequencies below, at, and above the resonance frequency of microbubbles were
      performed. Three specific effects on the pulse propagation (i.e., amplitude
      attenuation, phase changes, and harmonic generation) were studied. It was found
      that all these effects are dependent on the initial pulse amplitude, and their
      dependence on the initial phase of the pulse is shown to be insignificant. Two
      types of imaging errors are shown to result from this nonlinear propagation:
      first, that tissue can be misclassified as microbubbles; second, the
      concentration of microbubbles in the image can be misrepresented. It is found
      that these imaging errors are significant for all three pulse frequencies when
      the pulses transmit through a microbubble suspension of 6 cm in path length. It
      also is found that the first type of error is larger at the bubble resonance
      frequency.

PMID- 17186921
TI  - Long-term operation and performance of cryogenic sapphire oscillators.
AB  - Cryogenic sapphire oscillators (CSO) developed at the University of Western
      Australia (UWA) have now been in operation around the world continuously for many
      years. Such oscillators, due to their excellent spectral purity are essential for
      interrogating atomic frequency standards at the limit of quantum projection
      noise; otherwise aliasing effects will dominate the frequency stability due to
      the periodic sampling between successive interrogations of the atomic transition.
      Other applications, which have attracted attention in recent years, include tests
      on fundamental principles of physics, such as tests of Lorentz invariance. This
      paper reports on the long-term operation and performance of such oscillators. We
      compare the long-term drift of some different CSOs. The drift rates turn out to
      be linear over many years and in the same direction. However, the magnitude seems
      to vary by more than one order of magnitude between the oscillators, ranging from
      10(14) per day to a few parts in 10(13) per day.

PMID- 17186924
TI  - Reconstructions of shear modulus, Poisson's ratio, and density using approximate
      mean normal stress lambda epsilon alpha alpha as unknown.
AB  - As a differential diagnosis technique for living soft tissues, we are developing
      ultrasonic-strain-measurement-based shear modulus reconstruction methods.
      Previously, we reported three-dimensional (3-D) and 2-D reconstruction methods
      utilizing a typical Poisson's ratio very close to 0.5 (nearly-incompressible).
      However, because a decrease in the accuracy of the reconstructed value was
      confirmed to be due to the difference between the original value and the set
      value, we proposed 3-D and 2-D methods of reconstructing Poisson's ratio as well.
      Furthermore, we proposed methods of reconstructing density and dealing with
      dynamic deformation. However, due to tissue incompressibility, the
      reconstructions of shear modulus, Poisson's ratio, and density became unstable.
      In this report, to obtain stable, unique reconstructions, we describe a new
      reconstruction method using mean normal stress approximated by the product of one
      of Lame's constants X and volume strain epsilon alpha alpha as an unknown.
      Regularization is simultaneously applied to the respective distributions to
      decrease the instability of the reconstructions due to measurement errors of the
      deformation. This method also enables stable, unique reconstructions of shear
      modulus and density under the condition that the mean normal stress remains
      unknown. We also verify the effectiveness of this method through 3-D simulations,
      while showing erroneous artifacts occurring when 2-D and 1-D reconstructions are
      performed.

PMID- 17186925
TI  - Amplitude modulation drive to rectangular-plate linear ultrasonic motors with
      vibrators dimensions 8 mm x 2.16 mm X 1 mm.
AB  - In this paper, to exploit the contribution from not only the stators but also
      from other parts of miniature ultrasonic motors, an amplitude modulation drive is
      proposed to drive a miniature linear ultrasonic motor consisting of two
      rectangular piezoelectric ceramic plates. Using finite-element software, the
      first longitudinal and second lateral-bending frequencies of the vibrator are
      shown to be very close when its dimensions are 8 mm x 2.16 mm x 1 mm. So one
      single frequency power should be able to drive the motor. However, in practice
      the motor is found to be hard to move with a single frequency power because of
      its small vibration amplitudes and big frequency difference between its
      longitudinal and bending resonance, which is induced by the boundary condition
      variation. To drive the motor effectively, an amplitude modulation drive is used
      by superimposing two signals with nearly the same frequencies, around the
      resonant frequency of the vibrators of the linear motor. When the amplitude
      modulation frequency is close to the resonant frequency of the vibrator's
      surroundings, experimental results show that the linear motor can move back and
      forward with a maximum thrust force (over 0.016 N) and a maximum velocity (over
      50 mm/s).

PMID- 17186926
TI  - Perturbation analysis of frequency shifts in an electroelastic body under biasing
      fields.
AB  - We analyze the eigenvalue problem associated with small-amplitude vibrations
      superposed on finite-biasing fields in an electroelastic body. The widely used
      first-order perturbation integral by Tiersten is generalized in two different
      ways: a second-order perturbation analysis is given when the biasing fields are
      not infinitesimal and their second order effects need to be considered; a first
      order perturbation analysis is given when an eigenvalue is associated with more
      than one eigenvector (a degenerate eigenvalue).

PMID- 17186927
TI  - Recurrent RBFN-based fuzzy neural network control for X-Y-theta motion control
      stage using linear ultrasonic motors.
AB  - A recurrent radial basis function network (RBFN) based fuzzy neural network (FNN)
      control system is proposed to control the position of an X-Y-theta motion control
      stage using linear ultrasonic motors (LUSMs) to track various contours in this
      study. The proposed recurrent RBFN-based FNN combines the merits of self
      constructing fuzzy neural network (SCFNN), recurrent neural network (RNN), and
      RBFN. Moreover, the structure and the parameter learning phases of the recurrent
      RBFN-based FNN are performed concurrently and on line. The structure learning is
      based on the partition of input space, and the parameter learning is based on the
      supervised gradient decent method using a delta adaptation law. The experimental
      results due to various contours show that the dynamic behaviors of the proposed
      recurrent RBFN-based FNN control system are robust with regard to uncertainties.

PMID- 17186928
TI  - High-temperature 434 Mhz surface acoustic wave devices based on GaPO4.
AB  - Research into surface acoustic wave (SAW) devices began in the early 1970s and
      led to the development of high performance, small size, and high reproducibility
      devices. Much research has now been done on the application of such devices to
      consumer electronics, process monitoring, and communication systems. The use of
      novel materials, such as gallium phosphate (GaPO4), extends the operating
      temperature of the elements. SAW devices based on this material operating at 434
      MHz and up 800 degrees C, can be used for passive wireless sensor applications.
      Interdigital transducer (IDT) devices with platinum/zirconium metallization and
      1.4 microm finger-gap ratio of 1:1 have been fabricated using direct write e-beam
      lithography and a lift-off process. The performance and long-term stability of
      these devices has been studied, and the results are reported in this paper.

PMID- 17186929
TI  - Two-dimensional electroacoustic model of transducer array based on 1-3
      piezocomposite materials.
AB  - An analytical model is presented to achieve simultaneous prediction of the
      elementary electroacoustic response and directivity pattern of a one-dimensional
      (1-D) piezocomposite array. The theoretical approach was based on guided wave
      theory in a multilayered structure in which the 1-3 piezocomposite material is
      considered as a homogeneous piezoelectric plate. A matrix method was applied to
      simulate the displacement fields generated at the surface of the array when one
      element was excited with an electrical pulse. A test device was manufactured,
      then characterized through measurements of displacement performed with an
      interferometric laser probe when the array vibrated in air and in water. The
      experimental results are presented and compared with theory.

PMID- 17186930
TI  - Potential of acoustic imaging in the detection of nanometer gaps.
AB  - The potential of the water-immersion and dry-contact acoustic imaging techniques
      for detecting nanometer gaps embedded in silicon is studied. The sensitivity for
      detecting gaps of over 10 nm in height is governed only by the lateral resolution
      of the imaging and is independent of the height of the gap.

PMID- 17186931
TI  - Electrostatic transducers for micromechanical resonators: free space and solid
      dielectric.
AB  - Three electrostatic transduction methods are analyzed for a micromechanical,
      longitudinal mode, beam resonator. The conventional parallel plate transducer
      placed at the location of maximum displacement is compared to two solid,
      dielectric transducers internal to the resonator. Although the solid dielectric
      offers higher permittivity than the free-space-filled transducers, the
      unfavorable locations of the internal transducers reduce or even remove the
      performance advantage of the higher permittivity.

PMID- 17186932
TI  - Beyond respect for autonomy.

PMID- 17186933
TI  - The case of A.R.: the ethics of sibling donor bone marrow transplantation
      revisited.

PMID- 17186934
TI  - A compounding of errors: the case of bone marrow donation between non-intimate
      siblings.

PMID- 17186935
TI  - Duty and altruism: alternative analyses of the ethics of sibling bone marrow
      donation.

PMID- 17186936
TI  - The courage to stand up: the cultural politics of nurses' access to ethics
      consultation.

PMID- 17186937
TI  - Healthcare organizations as moral communities.

PMID- 17186938
TI  - Nurses and ethics consultation: growing beyond a rock and a hard place.

PMID- 17186939
TI  - Physician-nurse relationships and their effect on ethical nursing practice.

PMID- 17186940
TI  - Supporting pregnant women through difficult decisions: a case of prenatal
      diagnosis of osteogenesis imperfecta.

PMID- 17186941
TI  - Individuals, systems, and professional behavior.

PMID- 17186942
TI  - The residues determining differences in ion affinities among the alternative
      splice variants F, A, and B of the mammalian renal Na-K-Cl cotransporter (NKCC2).
AB  - Three alternatively spliced variants of the renal Na-K-Cl cotransporter (NKCC2)
      are found in distinct regions of the thick ascending limb of the mammalian
      kidney; these variants mediate Na(+)K(+)2Cl(-) transport with different ion
      affinities. Here, we examine the specific residues involved in the variant
      specific affinity differences, utilizing a mutagenic approach to change the
      NKCC2B variant into the A or F variant, with functional expression in Xenopus
      oocytes. The splice region contains the second transmembrane domain (TM2) and the
      putative intracellular loop (ICL1) connecting TM2 and TM3. It is found that the B
      variant is functionally changed to the F variant by replacement of six residues,
      half of the effect brought about by three TM2 residues and half by three ICL1
      residues. The involvement of the ICL1 residues strongly suggests that this region
      of ICL1 may actually be part of a membrane-embedded domain. Changing six residues
      is also sufficient to bring about the smaller functional change from the B to the
      A variant; three residues in TM2 appear to be primarily responsible, two of which
      correspond to residues involved in the B-to-F changes. A B-variant mutation
      reported in a mild case of Bartter disease was found to render the cotransporter
      inactive. These results identify the combination of amino acid variations
      responsible for the differences among the three splice variants of NKCC2, and
      they support a model in which a reentrant loop following TM2 contributes to the
      chloride binding and translocation domains.

PMID- 17186943
TI  - Chromatin-dependent cooperativity between site-specific transcription factors in
      vivo.
AB  - Accessing binding sites in DNA wrapped around histones in condensed chromatin is
      an obstacle that transcription factors must overcome to regulate gene expression.
      Here we demonstrate cooperativity between two transcription factors, the
      glucocorticoid receptor (GR) and nuclear factor 1 (NF1) to bind the mouse mammary
      tumor virus promoter organized as regular chromatin in vivo. This cooperativity
      is not observed when the promoter is introduced transiently into cells. Using RNA
      interference to deplete NF1 protein levels in the cells, we confirmed that NF1
      promotes binding of GR to the promoter. Furthermore, we observed a similar
      synergism between GR and NF1 binding on the endogenous 11beta-hydroxysteroid
      dehydrogenase promoter, also regulated by GR and NF1. Our results suggest that
      the chromatin architecture of the promoters does not permit strong association of
      GR in the absence of NF1. Therefore we propose that cooperativity among DNA
      binding factors in binding to their cognate recognition sites in chromatin may be
      an important feature in the regulation of gene expression.

PMID- 17186944
TI  - Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in
      macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol.
AB  - Liver X receptor (LXR) activation represents a mechanism to prevent macrophage
      foam cell formation. Previously, we demonstrated that partial inhibition of
      oxidosqualene:lanosterol cyclase (OSC) stimulated synthesis of the LXR agonist
      24(S),25-epoxycholesterol (24(S),25-epoxy) and enhanced ABCA1-mediated
      cholesterol efflux. In contrast to a synthetic, nonsteroidal LXR activator, TO
      901317, triglyceride accumulation was not observed. In the present study, we
      determined whether endogenous 24(S),25-epoxy synthesis selectively enhanced
      expression of macrophage LXR-regulated cholesterol efflux genes but not genes
      that regulate fatty acid metabolism. THP-1 human macrophages incubated with the
      OSC inhibitor (OSCi) RO0714565 (15 nM) significantly reduced cholesterol
      synthesis and maximized synthesis of 24(S),25-epoxy. Endogenous 24(S),25-epoxy
      increased ABCA1, ABCG1, and APOE mRNA abundance and consequently increased
      cholesterol efflux to apoAI. In contrast, OSCi had no effect on LXR-regulated
      genes LPL (lipoprotein lipase) and FAS (fatty acid synthase). TO-901317 (>or=10
      nM) significantly enhanced expression of all genes examined. OSCi and TO-901317
      increased the mRNA and precursor form of SREBP-1c, a major regulator of fatty
      acid and triglyceride synthesis. However, conversion of the precursor to the
      active form (nSREBP-1c) was blocked by OSCi-induced 24(S),25-epoxy but not by TO
      901317 (>or=10 nm), which instead markedly increased nSREBP-1c. Disruption of
      nSREBP-1c formation by 24(S),25-epoxy accounted for diminished FAS and LPL
      expression. In summary, endogenous synthesis of 24(S),25-epoxy selectively up
      regulates expression of macrophage LXR-regulated cholesterol efflux genes without
      stimulating genes linked to fatty acid and triglyceride synthesis.

PMID- 17186945
TI  - Microsomal prostaglandin E synthase-1 deficiency is associated with elevated
      peroxisome proliferator-activated receptor gamma: regulation by prostaglandin E2
      via the phosphatidylinositol 3-kinase and Akt pathway.
AB  - mPGES-1 (microsomal PGE synthase-1) is an inducible enzyme that acts downstream
      of cyclooxygenase (COX) and specifically catalyzes the conversion of
      prostaglandin (PG) H(2) to PGE(2) under basal as well as inflammatory conditions.
      In this study, using mouse embryo fibroblasts (MEFs) isolated from mice
      genetically deficient for the mPges-1 gene, we show basal elevation of peroxisome
      proliferator-activated receptor gamma (PPARgamma) expression (protein and mRNA)
      and transcriptional activity associated with reduced basal PGE(2). We further
      show that basal mPGES-1-derived PGE(2) suppresses the expression of PPARgamma
      through a cAMP-independent pathway involving phosphatidylinositol 3-kinase and
      Akt signaling. Using specific PPARgamma agonist (rosiglitazone), PPARgamma ligand
      (15-deoxy-Delta12,14-PGJ(2)), and PPARgamma inhibitor (GW9662), we confirm that
      activation of PPARgamma blocks interleukin-1beta-induced up-regulation of COX-2,
      mPGES-1, and their derived PGE(2). Furthermore, we demonstrate that up-regulation
      of PPARgamma upon genetic deletion of mPGES-1 is responsible for reduced COX-2
      expression under basal as well as interleukin-1beta-stimulated conditions. This
      study provides evidence for the first time that mPGES-1 deletion not only
      decreases proinflammatory PGE(2) but also up-regulates anti-inflammatory
      PPARgamma, which has the ability to suppress COX-2 and mPGES-1 expression and
      PGE(2) production. Thus, mPGES-1 inhibition may limit inflammation by multiple
      mechanisms and is a potential therapeutic target.

PMID- 17186949
TI  - Optical images of dose distributions in Gel-Fricke: dosimetric performances of
      the gel.
AB  - The purpose of this work was to examine the dosimetric performances of the
      radiochromic Fricke-Agarose-Xylenol Orange gel by optical measurements in order
      to perform dose reconstructions, in view of a future development for 3-D maps.
      Optical images and dose-response curves of the gel were obtained by a CCD-based
      device, originally designed for reading radiochromic films, that was modified to
      meet the optical properties of the dosemeter. With a resolution of 0.18 x 0.18 mm
      the optimum range of doses in which per cent uncertainty is lower than 2% was 3
      10 Gy. The minimum detectable dose, estimated as the absorbed dose corresponding
      to 3 SD above background, was 0.1 Gy. With a resolution of 1.98 x 1.98 mm the
      optimum range of doses in which per cent uncertainty is lower than 2% was 0.3-10
      Gy. The minimum detectable dose, estimated as the absorbed dose corresponding to
      3 SD above background, was 0.015 Gy. The comparison with alanine dosemeters in
      the dose range 7-10 Gy showed agreement within a few per cent and the same
      agreement was observed for the comparison with TLD in the range 1-3 Gy.

PMID- 17186946
TI  - A comprehensive proteomics and genomics analysis reveals novel transmembrane
      proteins in human platelets and mouse megakaryocytes including G6b-B, a novel
      immunoreceptor tyrosine-based inhibitory motif protein.
AB  - The platelet surface is poorly characterized due to the low abundance of many
      membrane proteins and the lack of specialist tools for their investigation. In
      this study we identified novel human platelet and mouse megakaryocyte membrane
      proteins using specialist proteomics and genomics approaches. Three separate
      methods were used to enrich platelet surface proteins prior to identification by
      liquid chromatography and tandem mass spectrometry: lectin affinity
      chromatography, biotin/NeutrAvidin affinity chromatography, and free flow
      electrophoresis. Many known, abundant platelet surface transmembrane proteins and
      several novel proteins were identified using each receptor enrichment strategy.
      In total, two or more unique peptides were identified for 46, 68, and 22 surface
      membrane, intracellular membrane, and membrane proteins of unknown subcellular
      localization, respectively. The majority of these were single transmembrane
      proteins. To complement the proteomics studies, we analyzed the transcriptome of
      a highly purified preparation of mature primary mouse megakaryocytes using serial
      analysis of gene expression in view of the increasing importance of mutant mouse
      models in establishing protein function in platelets. This approach identified
      all of the major classes of platelet transmembrane receptors, including
      multitransmembrane proteins. Strikingly 17 of the 25 most megakaryocyte-specific
      genes (relative to 30 other serial analysis of gene expression libraries) were
      transmembrane proteins, illustrating the unique nature of the
      megakaryocyte/platelet surface. The list of novel plasma membrane proteins
      identified using proteomics includes the immunoglobulin superfamily member G6b,
      which undergoes extensive alternate splicing. Specific antibodies were used to
      demonstrate expression of the G6b-B isoform, which contains an immunoreceptor
      tyrosine-based inhibition motif. G6b-B undergoes tyrosine phosphorylation and
      association with the SH2 domain-containing phosphatase, SHP-1, in stimulated
      platelets suggesting that it may play a novel role in limiting platelet
      activation.

PMID- 17186950
TI  - Impaired therapeutic vasculogenesis by transplantation of OxLDL-treated
      endothelial progenitor cells.
AB  - Previous in vitro studies have revealed that oxidized low density lipoprotein
      (OxLDL) has negative effects on the proliferation and activity of endothelial
      progenitor cells (EPCs). Here, we evaluated the effect of OxLDL on the
      therapeutic potential of EPCs in ischemia-induced neovascularization. EPCs
      derived from mobilized human peripheral blood mononuclear cells were cultured
      without or with OxLDL before transplantation. Hindlimb ischemia models were
      surgically induced in athymic nude mice, which then received an intracardiac
      injection of 3 x 10(5) EPCs. By laser Doppler perfusion image and ischemia damage
      score, we found that blood perfusion and ischemia damage were less well recovered
      in the OxLDL-treated EPC transplantation group than in controls. Histological
      examination showed fewer transplanted EPCs and lower capillary density in
      ischemic tissue. Local delivery of Stromal cell-derived factor (SDF-1) restored
      this defect and improved blood perfusion by recruiting OxLDL-treated EPCs to the
      ischemic area and increasing host capillary density. These results provide for
      the first time direct evidence that OxLDL impaired the therapeutic potential of
      EPCs in ischemia-induced neovascularization through an inhibitory effect on the
      migration, adhesion, and incorporation of EPCs into vasculature and/or entrapment
      in the perivascular region in vivo. A therapeutic strategy based on SDF-1
      administration ameliorated such defects and improved postischemic
      neovascularization.

PMID- 17186951
TI  - Association of human leukocyte antigen polymorphism with hepatitis B virus
      infection and genotypes.
AB  - Associations were studied between the polymorphism of northern Han Chinese
      leukocyte antigen (HLA) alleles and the outcomes of hepatitis B virus (HBV)
      infection and HBV genotypes. HLA-A, B, and DRB1 alleles in peripheral blood
      mononuclear cells (PBMCs) were detected by polymerase chain reaction (PCR) with
      sequence-specific primers. The PBMCs were collected from 61 persons who tested
      positive for hepatitis B surface antigen (HBsAg) for more than 6 months
      (Persistent group), 32 persons who tested negative for both HBsAg and HBV DNA but
      positive for both anti-HBc and anti-HBs (Recovered group), and 40 persons who
      tested negative for all serologic markers of HBV infection (Uninfected group).
      HBV genotypes in serum specimens from 56 of 61 patients with persistent HBV
      infection were determined by nested PCR with 6 pairs of HBV genotype-specific
      primers (A to F). The frequency of HLA-DRB1*12 was significantly higher in the
      Persistent group than in the Recovered group (P=0.004). HLA-A*02 was
      significantly higher in the Recovered group than in the Persistent group
      (P=0.044). HLA-DRB1*15 was significantly higher in the HBV genotype B group than
      in the C group (P=0.013). These findings suggested that there were associations
      not only between HLA polymorphisms and outcomes of HBV infection but also between
      HLA polymorphisms and the infected HBV genotypes.

PMID- 17186952
TI  - Salmonella enterica serovar Kentucky: antimicrobial resistance and molecular
      analysis of clinical isolates from the Slovak Republic.
AB  - A collection of 68 isolates of Salmonella enterica serovar Kentucky collected
      during the period 2003-2004 from humans in two geographical regions in the Slovak
      Republic was studied. The original isolate of this serovar was associated with
      travel to Egypt, and the emergence of other isolates was due to the nosocomial
      spread of this strain in two hospitals. Antimicrobial susceptibility testing,
      class I integrons content, pulsed-field gel electrophoresis (PFGE) analysis and
      plasmid DNA profiles were performed on all isolates. A high proportion (89.7%) of
      the isolates was multidrug-resistant, while 67 strains expressed resistance
      against ciprofloxacin. By sequence analysis of randomly selected strains, the
      point mutations in quinolone resistance-determining region of the DNA gyrase were
      found. The S. Kentucky isolates investigated were determined to be clonally
      related by PFGE as well as plasmid DNA analysis.

PMID- 17186953
TI  - A two-step strategy for detecting intrauterine cytomegalovirus infection with
      clinical manifestations in the mother, fetus, and newborn.
AB  - We selected a high-risk group based on clinical manifestations and performed
      virological tests to detect intrauterine cytomegalovirus (CMV) infection. We
      tested the efficacy of this detection protocol in this study. We analyzed 2,309
      newborns at 22 weeks or more of gestation from January 1992 to December 2000.
      Clinical manifestations of the mother, fetus, and newborn were used in the
      initial step to identify the high-risk group. For the high-risk group, if the
      causes of clinical manifestation remained unclear, we assayed for CMV DNA in the
      amniotic fluid, umbilical cord blood, or newborn urine using polymerase chain
      reaction (PCR) as a second step. Positive PCR results were confirmed by isolating
      CMV. The initial step detected 287 high-risk cases from 2,309 deliveries. In this
      group, 100 cases did not have reasonable explanations for the clinical
      manifestation. In the second-step PCR, intrauterine CMV infection was diagnosed
      in 10 of 100 cases (10%). The initial clinical classification reduced the
      proportion of cases needing laboratory investigation to 4%. Thus, our strategy
      detected intrauterine CMV infection in as many as 10% of high-risk patients after
      the first step, which is much higher than the general screening rate.

PMID- 17186954
TI  - Duration of the metronidazole-containing regimen for eradication of Helicobacter
      pylori infection in northern Japan.
AB  - Metronidazole is often used to eradicate clarithromycin-resistant Helicobacter
      pylori. The aim of this study was to determine the appropriate duration of
      metronidazole-containing treatment for the eradication of H. pylori infection in
      northern Japan. We enrolled 83 H. pylori-positive patients in whom first-line
      triple therapy consisting of a proton pump inhibitor, amoxicillin and
      clarithromycin had failed. Prior to the second-line therapy, patients underwent
      endoscopy to obtain H. pylori strains to test the susceptibility to antibiotics.
      Patients were administered lansoprazole (30 mg b.d.), amoxicillin (750 mg b.d.)
      and metronidazole (250 mg b.d.) for 5 or 7 days, and the treatment results were
      tested by (13)C-UBT. None of the isolated H. pylori strains was amoxicillin- or
      metronidazole-resistant. All the patients completed the regimen without major
      adverse effects. The eradication rate was 95.1% (39/41; 95% confidence interval
      [CI], 83.5-99.4%) in the 41 patients who were treated for 5 days and 95.2%
      (40/42; 95% CI, 83.8-99.4%) in the 42 patients treated for 7 days. The results
      suggest that 5 days could be a sufficient duration for triple therapy of
      lansoprazole, amoxicillin and metronidazole as a second-line H. pylori
      eradication therapy in areas where metronidazole-resistant strains are rare.

PMID- 17186955
TI  - Clinical study on the efficacy and safety of intravenous itraconazole infusion
      for the treatment of invasive fungal infection in china.
AB  - Itraconazole has a broad spectrum of activity against the most common fungal
      pathogens. Prior problems with absorption in severely ill patients have been
      overcome with the introduction of an oral solution and an intravenous
      preparation. An open-labeled, non-competitive, multicenter phase IV study was
      conducted to investigate the efficacy and safety of itraconazole administered
      intravenously for the treatment of invasive fungal infections in Chinese
      patients. Patients were treated with itraconazole intravenously for 2 weeks (200
      mg twice daily for 2 days, then 200 mg once daily for 12 days) followed by 28
      days of oral capsules (200 mg twice daily). Efficacy evaluation included an
      assessment of the clinical efficacy, fungal efficacy and total efficacy on days
      14 and 42. Of 156 evaluable patients, 35 patients had proven and 62 suspected
      invasive fungal infections, and 59 patients were treated empirically. On day 14
      the total efficacy rate in patients with proven infection was 54.3% (19/35; 95%
      confidence interval [CI], 37-71%) and on day 42 it was 65.7% (23/35; 95% CI, 48
      81%). The most common adverse events were hypokalemia (13.5%), gastrointestinal
      disorders (12.8%), elevation of liver enzymes (10.9%) and increase of bilirubin
      (8.3%). Itraconazole intravenously followed by oral capsules is thus tolerated
      and effective in severely ill patients with proven invasive fungal infection.

PMID- 17186956
TI  - "Syndromic surveillance within a hospital" for the early detection of a
      nosocomial outbreak of acute respiratory infection.
AB  - We have performed intra-hospital syndromic surveillance to rapidly detect
      nosocomial acute respiratory infection outbreaks in both inpatients and health
      care workers in a hospital. Syndromic surveillance allows the rapid detection of
      sudden outbreaks, including infections caused by unknown pathogens. This approach
      depends on the identification of specific "symptoms" as signs of a possible
      outbreak, with no need for specific diagnoses. Moreover, syndromic surveillance
      is quick, easy, and inexpensive. Nosocomial infection surveillance is usually
      performed on inpatients only. However, during the outbreaks of SARS and seasonal
      influenza, for example, many hospital personnel were infected. In cases of this
      kind, in order to quickly detect the prevalence of such infections, a
      surveillance system that includes hospital personnel is essential. This
      surveillance is promising as a strategy to prepare for re-outbreaks of SARS and
      the emergence of novel influenza pandemics.

PMID- 17186957
TI  - Microbial sensitivity pattern in urinary tract infections in children: a single
      center experience of 1,177 urine cultures.
AB  - Urinary tract infection is one of the most common diseases in children. Early
      diagnosis and comprehensive treatment can significantly decrease late serious
      complications. Knowledge of the sensitivity and resistance pattern of
      uropathogens in specific geographical locations is an important factor for
      choosing suitable antibacterial treatment. This study was conducted in order to
      evaluate the antibacterial resistance of urinary pathogens at Mofid Children's
      Hospital between March 2000 and August 2001. Positive urine cultures from 1,177
      children aged less than 12 years (mean age, 31.7 months; female to male ratio,
      2:1) were studied. Cultures were performed on urine samples obtained by sterile
      urine bags in infants and midstream urine in older children; if samples were
      contaminated then a suprapubic sample was taken in infants. Sensitivity was
      measured by the disc diffusion method using the NCCLS protocol. The most
      prevalent urinary pathogen was Escherichia coli (666 cases, 56.6%). Overall, the
      lowest resistance rate of microorganisms was that against ciprofloxacin (6.7%)
      and the highest resistance rate was that against penicillin (83%). A comparison
      of these data with those of other countries shows that there is considerable
      geographic variation in bacterial patterns of sensitivity and resistance
      properties. Therefore, the selection of antibiotics for empiric therapy should be
      based on the sensitivity and resistance pattern of uropathogens in the respective
      city.

PMID- 17186958
TI  - A simplified PCR methodology for semiquantitatively analyzing dengue viruses.
AB  - The standard methodology for titrating dengue viruses, the plaque assay, is slow,
      time consuming and relatively expensive. Other methods require machinery that may
      not be routinely accessible to all researchers, particularly those in developing
      nations. We therefore sought to develop a rapid, simplified semiquantitative
      polymerase chain reaction (PCR) methodology based on the use of a template mimic.
      In particular, it was desired that the mimic should be applicable for use a DNA
      template to avoid the requirement for producing an in vitro RNA transcript. A 511
      base pair fragment of the capsid-PrM junction of dengue serotype 4 was cloned
      into pGEM-T Easy vector and subjected to splicing overlap extension-PCR to
      generate a 160 base pair deletion. The deleted plasmid mimic competed
      competitively against the parent plasmid as well as the first strand cDNA of all
      four dengue viruses. The primers used are specific for the dengue virus, and no
      product was seen with first strand cDNA from a closely related flavivirus,
      Japanese encephalitis virus. Under the conditions used, accurate quantitation of
      the dengue viruses in the range of 10(3) to 10(6) pfu can be achieved in a single
      day, as opposed to the 7 days required for conventional plaque assay.

PMID- 17186959
TI  - Validation of urinary antigen test for Streptococcus pneumoniae in patients with
      pneumococcal pneumonia.
AB  - The study was undertaken to prospectively evaluate a Streptococcus pneumoniae
      urinary antigen test for diagnosis of pneumococcal pneumonia among patient and
      control groups between 2004 and 2006. Microbiological analysis for these patients
      included Gram staining for sputum, sputum and blood culture. Nonconcentrated
      urine samples were tested using an immunochromatographic assay, the NOW
      S.pneumoniae antigen test. The urinary antigen test was positive in 9 (15.3%) of
      59 patients enrolled in the study and in 8 (73%) of 11 patients with pneumococcal
      pneumonia confirmed by conventional methods. The test revealed a sensitivity of
      72.7% and a specificity of 97.6% with conventional microbiological criteria used
      as the reference standard. The positive predictive value was 88.9% and the
      negative predictive value was 93%. We concluded that the urinary antigen test can
      supplement conventional microbiological tests in the diagnosis of pneumococcal
      pneumonia.

PMID- 17186960
TI  - Tularemia re-emerging in European part of Turkey after 60 years.
AB  - The aim of this study was to investigate a tularemia outbreak in the Thrace
      region of Turkey. The outbreak occurred in Demirkoy village of Edirne, in 2005.
      Of 400 villagers, 266 were examined and their sera were taken. Throat swabs and
      lymph node aspirates were cultured. Specific antibodies in patients and domestic
      animals were screened by a microagglutination test. PCR assays and cultures of
      the samples of patients, animal tissues, and water sources were performed, along
      with active surveillance to identify risk factors. Seven out of 10 cases were
      diagnosed as oropharyngeal form; the remaining three patients were asymptomatic.
      The cultures for tularemia were negative; however, PCR assays were positive in
      one lymph node aspirate and in water from one spring. Some animals had the
      specific antibody at low levels. Increased rodent population in the vicinity,
      exposure to wild rabbits, and drinking from one of the springs were identified as
      risk factors with the risk ratios (and 95% confidence interval) of 10.5 (10.3
      10.7), 6.5 (5.43-7.57), and 2.1 (1.1-2.5), respectively. Therapeutic and
      preventive measures were taken. When tularemia cases have been detected in a
      region even a few decades earlier, tularemia should be considered in the
      differential diagnosis of patients.

PMID- 17186961
TI  - Detection of adenovirus DNA in throat swabs and blood by SYBR green real-time PCR
      assay in patients with adenovirus-associated tonsillitis.
AB  - The adenovirus DNA load ranged from 10(5) to 10(10) copy/mL and from 10(4) to
      10(7) copy/mL in throat swabs and blood from patients with adenovirus-associated
      exudative tonsillitis, respectively. The copy number of adenovirus DNA in blood
      was positively correlated with the duration of the fever.

PMID- 17186962
TI  - Characteristics of Streptococcus suis isolated from patients in Japan.
AB  - Seven cases of Streptococcus suis infection in Japan during 1994 and 2006 were
      summarized. All cases had porcine exposure and five of them had hand skin injury
      during the exposure. Five cases presented symptoms of meningitis, three presented
      symptoms of sepsis, and one resulted in sudden death. All of the isolated S. suis
      belonged to Lancefield's group D and to serotype 2. They were susceptible to
      penicillin G, ampicillin, cefotaxime, and ciprofloxacin. However, six of them
      were resistant to both erythromycin and clindamycin, and four were also resistant
      to minocycline. Multilocus sequence typing of six isolates showed that they
      belonged to sequence type (ST) 1, and their pulsed-field gel electrophoresis
      (PFGE) patterns were similar. The remaining isolate was ST28 and its PFGE pattern
      was distinct from those of the others.

PMID- 17186963
TI  - Infection with HIV and intestinal parasites among street dwellers in Gondar city,
      northwest Ethiopia.
AB  - In Ethiopia human immunodeficiency virus (HIV) infection is a major health and
      socioeconomic problem. Sex workers, youth, and mobile populations all show
      increasing prevalence of HIV. However, there is currently no information about
      the seroprevalence of HIV and the knowledge of HIV among street dwellers in the
      country. To fill this gap, 404 street dwellers residing in Gondar, northwest
      Ethiopia, were included in this cross-sectional study. Socio-demographic data,
      factors that prompted the subjects to become street dwellers, and their knowledge
      about HIV were all assessed using a structured questionnaire. Stool samples for
      diagnosis of intestinal parasites and venous blood for HIV antibody testing were
      collected and processed following standard procedures. Poverty-associated
      movement to urban areas in search of work was reported as a major factor that
      forced them to live in the streets, followed by divorce, family death, and
      addiction and peer pressure. One or more intestinal parasites were found in 67.6%
      of the street dwellers. Multiple parasitic infections were detected in 27.7%. The
      prevalence of HIV in the street dwellers was 6.9%. Fifty-nine (16.6%)
      participants responded that HIV can be transmitted by eating food together.
      Seventy-three (18%) believed an infected needle cannot transmit HIV, while 51
      (12.6%) said HIV can be transmitted by hand shaking. One hundred ninety-two
      (47.5%) responded that antiretroviral therapy will not prolong the life of HIV
      infected individuals. In summary, the prevalence of HIV and intestinal parasitic
      infection was quite high among street dwellers in Gondar. Therefore, strategies
      to control HIV and other infectious diseases should include this group, and
      regular mass deworming may help to reduce the burden of infection.

PMID- 17186964
TI  - Annual incidence of tsutsugamushi disease in Miyazaki prefecture, Japan in 2001
      2005.

PMID- 17186965
TI  - Two outbreaks caused by Salmonella Derby and S. Anatum at grilled-meat
      restaurants in Fukuoka city.

PMID- 17186966
TI  - Food poisoning outbreak of Salmonella enteritidis caused by box lunch in Shiga
      prefecture, Japan.

PMID- 17186967
TI  - Outbreak of enterohemorrhagic Escherichia coli O157 attributed to a grilled-meat
      restaurant.

PMID- 17186968
TI  - An outbreak of Campylobacter jejuni food poisoning caused by secondary
      contamination in cooking practice at a high school.

PMID- 17186969
TI  - Enterotoxigenic Escherichia coli O6:H16 food poisoning outbreak in prisons.

PMID- 17186970
TI  - Impact of cutting balloon angioplasty (CBA) prior to bare metal stenting on
      restenosis.
AB  - BACKGROUND: While stent restenosis and late thrombosis still occur even with drug
      eluting-stents (DES), there remains a need to explore other strategies for
      preventing restenosis. METHODS AND RESULTS: Five hundred and twenty-one patients
      were randomized: 260 to cutting-balloon angioplasty (CBA) before bare-metal stent
      (CBA-BMS) and 261 to balloon-angioplasty (BA) before BMS (BA-BMS). Intravascular
      ultrasound (IVUS)-guided procedures were performed in 279 (54%) patients and
      angiographic guidance was used in the remainder. Minimal lumen diameter was
      significantly greater in CBA-BMS than BA-BMS (2.65+/-0.40 mm vs 2.52+/-0.4 mm,
      p<0.01) and % diameter stenosis (%DS)-post was less in CBA-BMS than BA-BMS
      (14.0+/-5.9% vs 16.3+/-6.8%, p<0.01). %DS-follow-up was subsequently less in CBA
      BMS than BA-BMS (32.4+/-15.1% vs 35.4+/-15.3%, p<0.05) associated with lower
      rates of restenosis in CBA-BMS than BA-BMS (11.8% vs 19.6%, p<0.05) and less
      target lesion revascularization (TLR) in CBA-BMS than BA-BMS (9.6% vs 15.3%,
      p<0.05). Patients were divided into 4 groups based on the device used before
      stenting and IVUS use (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA
      BMS: 142; and Angio-BA-BMS: 119). At follow-up IVUS-CBA-BMS had a significantly
      lower restenosis rate (6.6%) than Angio-CBA-BMS (17.9%), IVUS-BA-BMS (19.8%) and
      Angio-BA-BMS (18.2%, p<0.05). CONCLUSIONS: Restenosis and TLR were significantly
      lower in CBA-BMS than BA-BMS. This favorable outcome was achieved because of the
      lower restenosis rate conferred by the IVUS-guided-CBA-BMS strategy (6.6%). The
      restenosis rates obtained with this strategy were comparable to those achieved
      with DES.

PMID- 17186971
TI  - Association of creatinine clearance and in-hospital mortality in patients with
      acute coronary syndromes: the GREECS study.
AB  - BACKGROUND: The relationship between renal dysfunction and mortality in patients
      with myocardial infarction (MI) has been extensively investigated, but there are
      limited data about this relationship in patients presenting with non-ST-segment
      elevation MI and unstable angina. Therefore, the aim of the present study was to
      investigate whether renal insufficiency is an independent predictor for in
      hospital mortality among such patients. METHODS AND RESULTS: Two thousand a
      hundred and seventy-two patients presenting with acute coronary syndrome (ACS) in
      6 Greek hospitals were enrolled. Creatinine clearance rates were estimated by the
      Cockcroft-Gault formula. Five percentage of patients presented with severe renal
      dysfunction, 27% with moderate dysfunction and the other 68% were normal.
      Patients with moderate or severe renal dysfunction were older, more likely to be
      women and more likely to have history of hypertension and diabetes mellitus
      compared with those with normal renal function. In comparison with patients with
      normal renal function, those with moderate and severe renal dysfunction were
      respectively 3- and 12-fold more likely to die. Moreover, moderate and severe
      renal insufficiency continued to be a prognostic factor for mortality, even after
      controlling for potential confounders. CONCLUSIONS: Creatinine clearance rate is
      an important independent predictor of in-hospital mortality, so patients with ACS
      complicated by renal dysfunction should receive more aggressive medical care.

PMID- 17186972
TI  - Success rate of implantation and mid-term outcomes of the sirolimus-eluting
      stent.
AB  - BACKGROUND: The sirolimus-eluting stent (SES) is currently the sole drug-coated
      stent approved for use in Japan, but there are few reports on its safety and
      outcomes in Japan. METHODS AND RESULTS: From May 2004 to February 2005, a total
      of 297 patients with 402 lesions were treated with SES at 6 hospitals in the
      Kansai district. Follow-up angiography was performed in 82% of the patients and
      80% of the lesions at 182+/-35 days after stenting. Coronary stenosis was
      evaluated using quantitative coronary angiography. Clinical and angiographic data
      were analyzed. Minimum lesion diameter was 0.75+/-0.52 mm and the reference
      diameter was 2.81+/-0.47 mm before stenting. The SES successfully dilated 99.5%
      of the lesions with few major adverse cardiac events. Restenosis occurred in 4.0%
      and the target lesion revascularization rate was 3.7%. Restenosis correlated with
      chronic hemodialysis, calcification, occlusion, ostial lesions, lesions kinked>45
      degrees, right coronary artery (RCA) lesions and lesions at the ostium of the
      RCA. CONCLUSION: SES demonstrated a high rate of successful implantation with few
      complications, and mid-term outcomes were excellent. Patients with lesions at the
      ostium of the RCA or under chronic hemodialysis developed restenosis.

PMID- 17186973
TI  - Impact of abnormal glucose tolerance, hypertension and other risk factors on
      coronary artery disease.
AB  - BACKGROUND: The degree to which abnormal glucose tolerance contributes to the
      development of coronary artery disease (CAD) has not been clarified in Japanese.
      The relationship between abnormal glucose tolerance and severity of coronary
      artery stenosis, as well as the contributions of hypertension, diabetes and other
      risk factors for CAD to recurrence of the disease, were investigated in the
      present study. METHODS AND RESULTS: The subjects were 474 consecutive patients
      (mean age: 63.8+/-11.3 years) with suspected CAD who were admitted to Sapporo
      Medical University Hospital during April 1, 1997 to March 31, 2004. The coronary
      index and stenosis score were higher in subjects with diabetes mellitus (DM) and
      in subjects with impaired fasting glucose (IFG) and impaired glucose tolerance
      (IGT) than in subjects with normal glucose tolerance (NGT). Ischemic episodes
      recurred during the observation period (mean 2.5 years) in 61 of 341 patients
      diagnosed as having CAD. In the follow-up subjects, systolic blood pressure (SBP)
      was significantly higher in the recurrence group than in the non-recurrence
      group, and SBP was a significant variable in logistic regression analysis after
      adjustment for age, gender, hemoglobin A1c, total cholesterol, body mass index,
      smoking history, family history and stenosis score. The relative risk of
      recurrence became 1.7-fold higher with a rise in SBP of 10 mmHg (95% confidence
      interval: 1.252-2.250). Analysis of the relationship between glucose tolerance
      and recurrence showed that the rate of recurrence was higher in patients with
      IFG+IGT+DM than in those with NGT. CONCLUSIONS: CAD progresses not only in
      patients with DM but also in those with IGT. The rate of recurrence of ischemic
      episodes increases in individuals with IGT or DM, and suggesting that
      hypertension is a risk factor for recurrence of ischemic episodes. Management of
      glucose tolerance and blood pressure is therefore important for prevention of CAD
      in Japanese.

PMID- 17186974
TI  - Metabolic syndrome and C-reactive protein in the general population: JMS Cohort
      Study.
AB  - BACKGROUND: In recent years some studies have shown that metabolic syndrome (MS)
      is associated with inflammation, indicated by high-sensitivity C-reactive protein
      (hsCRP), but there have been few population-based studies, especially in Japan.
      METHODS AND RESULTS: The study subjects were 2,191 men and women examined between
      1992 and 1995 with the necessary data to ascertain MS as part of the Jichi
      Medical School Cohort Study. CRP was measured by nephelometry. There were 109
      subjects defined as having MS (5.0%), and the proportion of MS cases was higher
      in men (9.4%) than in women (1.8%). Geometric mean and median CRP in the MS group
      was higher than that in the non-MS (geometric mean; p<0.001, median: 0.312 mg/L
      in MS and 0.122 mg/L). Proportion of MS increased with CRP, after the subjects
      were divided by tertile of CRP (odds ratio, 95% confidence interval 1st tertile
      as a reference; 2nd tertile: 2.9, 1.5-5.9, 3rd tertile: 5.7, 3.1-11.1).
      CONCLUSION: Inflammation, measured by the concentration of hsCRP, was elevated in
      cases of MS in the general Japanese population. Longitudinal data should be
      examined in the future.

PMID- 17186975
TI  - Do valsartan and losartan have the same effects in the treatment of coronary
      artery disease?
AB  - BACKGROUND: Many angiotensin II type 1 receptor blockers (ARBs) are available for
      clinical use, but because they do not all have the same effects, the present
      study investigated whether all benefits conferred by ARBs are class effects.
      METHODS AND RESULTS: Study 1 was a case-control study of patients with coronary
      artery disease, which showed that a non-depressor dose of valsartan significantly
      decreased the rate of target lesion revascularization at 6 months after stenting
      compared with the control group without ARB treatment. In Study 2, 44 patients
      with acute myocardial infarction who randomly received an initial lower dose of
      either valsartan or losartan after stenting were evaluated. The late loss and
      decrease in %diameter stenosis in the valsartan group were significantly lower
      than those in the losartan group as assessed by quantitative coronary angiography
      after 6 months. In addition, the valsartan group showed a significantly lower
      expression of intracellular adhesion molecule-1 and L-selectin. CONCLUSION: A non
      depressor dose of ARB may have beneficial effects on coronary restenosis that are
      associated with the regulation of adhesion molecules, and these effects might not
      be a class effect of ARBs.

PMID- 17186976
TI  - D-allele of ACE polymorphism is associated with increased magnitude of QT
      dispersion prolongation in elderly Chinese: 4-year follow-up study.
AB  - BACKGROUND: There has not been a longitudinal investigation of the influence of
      angiotensin-converting enzyme (ACE) insertion/deletion and angiotensinogen (AGT)
      M235T gene polymorphisms on repolarization parameters, such as QT dispersion
      (QTd) and the peak and the end of the T-wave interval (Tpe). METHODS AND RESULTS:
      Electrocardiographys were recorded from 106 elderly Chinese at baseline, and 2nd
      and 4th year follow-up. The corrected QT (QTc), QTd, QTc dispersion (QTcd) and
      Tpe were manually calculated. Average age was 72.7+/-4.1 years (range 62-81).
      QTd, QTcd and Tpe were significantly prolonged (all p<0.001 at the 2nd and 4th
      year). At the 4th year the magnitude of the QTd prolongation, but not Tpe, was
      significantly higher in subjects carrying the ACE D allele than non-D-allele
      carriers (p=0.001), as was QTcd (p=0.002). This association was still significant
      in the multivariate analyses (p<0.001 and p=0.001 for QTc and QTcd,
      respectively). No significant correlation was found between repolarization
      parameters and AGT genotype. CONCLUSIONS: This longitudinal study shows that the
      ageing process is associated with prolongation of QTd, QTcd and Tpe after 4 years
      follow-up. The elderly Chinese subjects with the ACE D-allele had greater
      prolongation QTd and QTcd.

PMID- 17186977
TI  - Efficacy of amiodarone for preventing the recurrence of symptomatic paroxysmal
      and persistent atrial fibrillation after cardioversion.
AB  - BACKGROUND: It has been previously reported that the efficacy of class I
      antiarrhythmics in preventing the recurrence of symptomatic paroxysmal and
      persistent atrial fibrillation (AF) is limited when AF lasts for 48 h or more.
      However, it is unclear whether the efficacy of amiodarone, a class III drug, is
      superior to class I antiarrhythmics in patients with long-lasting AF. METHOD AND
      RESULTS: The relationship between the duration of tachycardia and the efficacy of
      amiodarone in preventing recurrence of tachycardia was examined in 55 patients
      (37 men, 18 women, mean age 68+/-9 years) to whom amiodarone was administered
      after electrical or pharmacological cardioversion for paroxysmal and persistent
      AF. In 26 patients, paroxysmal and persistent AF ceased within 48 h after onset
      (Group A), and in the other 29 patients, it ceased after 48 h (Group B). Patient
      characteristics and actuarial recurrence-free rates were compared between the 2
      groups. The mean follow-up period was 30+/-11 months. No statistically
      significant difference between the groups was found in patient characteristics.
      Actuarial recurrence-free rates in Group A and B at 1, 3, 6, 9, and 12 months
      were 100%, 81%, 69%, 62%, and 54%, and 93%, 79%, 66%, 52%, and 48%, respectively
      (p=NS at 12 months). The period of maintenance of sinus rhythm was 14.7+/-3.2
      months in group A and 13.3+/-3.3 months in group B (mean+/-SE, p=NS). CONCLUSION:
      In the case of amiodarone, efficacy for maintaining sinus rhythm after
      cardioversion of AF was not biased by the duration of arrhythmia. This
      observation suggests amiodarone is effective in maintaining normal sinus rhythm
      after cardioversion, even in patients with long-lasting AF and electrical atrial
      remodeling.

PMID- 17186978
TI  - Thoracic aortic plaque enhances hypercoagulability in patients with nonrheumatic
      atrial fibrillation.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) are at risk for
      thromboembolism, and coexistent cardiovascular diseases could affect their
      prothrombotic profiles. The relationship between plasma hemostatic markers and
      aortic atherosclerosis was determined in patients with AF or in sinus rhythm
      (SR). METHODS AND RESULTS: Sixty patients with nonrheumatic AF and 46 patients in
      SR who underwent transesophageal echocardiography and did not receive
      anticoagulant therapy constituted the study group. Markers for platelet activity
      (platelet factor 4 and beta-thromboglobulin), thrombotic status (thrombin
      antithrombin III complex and prothrombin fragment 1+2 (F1+2)) and fibrinolytic
      status (plasmin-alpha2-plasmin inhibitor complex (PIC) and D-dimer) were
      determined. Levels of F1+2, PIC and D-dimer were higher in AF patients with
      severe atheroma than in those without severe atheroma (p<0.05). In patients in
      SR, hemostatic markers were not significantly increased even if they had severe
      aortic atherosclerosis. AF (Odds ratio (OR) 4.06, p=0.04) and age>or=75 years (OR
      3.98, p=0.02) were independently predictive of elevated D-dimer levels and severe
      atheroma was predictive of elevated F1+2 levels (OR 5.52, p=0.04). CONCLUSIONS:
      Elderly patients with AF and severe aortic atherosclerosis might be in a
      prothrombotic state, and could benefit from intensive antithrombotic therapy.

PMID- 17186979
TI  - Different effect of the pure Na+ channel-blocker pilsicainide on the ST-segment
      response in the right precordial leads in patients with normal left ventricular
      function.
AB  - BACKGROUND: The response of the ST-segment in the right precordial leads to Na+
      channel blockers in patients without structural heart disease and a typical
      Brugada-type ECG has not been fully elucidated. METHODS AND RESULTS: A
      pilsicainide challenge test was performed in 161 patients and according to
      recently established ECG criteria and an organized computer algorithm, the ST
      morphology was classified and the maximum increase in the J wave amplitude
      (maxDeltaJ) from the standard and high right precordial leads V1-3 was examined.
      Before the test, subjects exhibiting type 1 ECG in the standard leads were
      excluded. After administering pilsicainide, type 1 ECGs in the standard leads
      were observed in 31 cases and a maxDeltaJ of >or=200 microV was observed in 29
      cases (23 type 1, 2 type 2/3 and 4 normal ECGs). In the additional higher right
      precordial leads, type 1 ECGs were observed in 55 cases and a maxDeltaJ of
      >or=200 microV was observed in 45 cases (42 type 1 and 3 type 2/3 ECGs).
      CONCLUSIONS: A maxDeltaJ>or=200 microV induced by pilsicainide, including that
      measured in the high right precordial leads, was associated with a change mainly
      to a type 1 ECG.

PMID- 17186981
TI  - Histopathological features of the resected left atrial appendage as predictors of
      recurrence after surgery for atrial fibrillation in valvular heart disease.
AB  - BACKGROUND: A histopathological assessment of left atrial appendages (LAA)
      resected during surgical treatment for atrial fibrillation (AF) was made, with
      the aim of improving the prediction of postoperative AF recurrence. METHODS AND
      RESULTS: This clinicopathological study involved 57 surgical cases of valvular AF
      and 34 age- and sex-matched control autopsy cases with a history of sinus rhythm.
      LAA from the cases with valvular AF showed greater hypertrophy of cardiomyocytes
      (p<0.0001), greater nuclear enlargement (p<0.0001), more bizarre nuclei (BN;
      p<0.0001), and more intercellular fibrosis (ICF; p<0.001). Partial disarray of
      cardiomyocytes and fatty infiltration were recognized in both the AF and control
      groups. Thirty-seven cases had maintained sinus rhythm after surgery from 7
      months to 10 years. AF recurred within a month of surgery in 17 and after a month
      in 3; there was no significant difference in histopathological features between
      them. These 20 cases had more cellular hypertrophy (p<0.025), nuclear enlargement
      (p<0.025), BN (p<0.01), and ICF (p<0.025) than those who maintained sinus rhythm
      after surgery. CONCLUSIONS: The histopathological findings for LAA reflected the
      underlying valvular diseases; however, the most reliable predictors of
      postoperative AF recurrence were hypertrophy of cardiomyocytes, bizarre shaped
      nuclei, and extensive ICF.

PMID- 17186980
TI  - Characteristic features of QRST integral mapping in patients with high risk
      Brugada syndrome.
AB  - BACKGROUND: The characteristic features of QRST integral mapping in the Brugada
      type resting ECG of patients at a high risk for life-threatening ventricular
      arrhythmias were examined. METHODS AND RESULTS: QRST integral mapping was
      performed in 11 Brugada-type ECG patients with histories of aborted sudden death,
      spontaneous ventricular tachycardia and fibrillation (VT/VF) or programmed
      electric stimulation-inducible VT/VF (high risk group); 13 Brugada-type ECG
      patients without a history of such events (low risk group); and 21 age-matched
      healthy controls. Individual QRST isointegral maps revealed the minimum integral
      in the mid-to-right upper chest in 100% and 85% of the control and low risk
      groups, respectively, whereas this integral was 64% in the upper right back of
      the high risk group (p<0.05). On the QRST integral departure maps, the abnormal
      positive departure area (integral value>or=+2 standard deviation) was located in
      the mid-to-right upper chest in 82% and 8% of the high and low risk groups,
      respectively (p<0.05). During the follow-up period, sudden death or VF occurred
      in 4 of 6 high risk patients with both the abnormal findings. CONCLUSION: The
      abnormal positive departure area in the mid-to-right upper chest and the minimum
      QRST integral in the right upper back were distinct hallmarks for screening
      patients with the high risk Brugada-type ECG.

PMID- 17186982
TI  - N-terminal ProBNP levels can predict cardiac failure after cardiac surgery.
AB  - BACKGROUND: The aim of this study was to evaluate the relationship between the
      preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) level and the
      need for the inotropic support in the early postoperative period of patients
      undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: The
      patients were divided into 2 groups: NT-proBNP level<220 pg/ml (group A, n=26) or
      >220 pg/ml (group B, n=26). The normal value for NT-proBNP level was accepted as
      <220 pg/ml. The cardiac output was measured on arrival in intensive care and at
      the 16th hour. The groups were compared with respect to early postoperative
      hemodynamic measurements, urinary output, use of inotropic agents and requirement
      for additional cardiac-assist devices. Left ventricular ejection fraction,
      cardiac output and cardiac index were lower in group B and inotropic agents were
      used for a longer period of time and at higher doses in this group (p<0.05).
      CONCLUSION: Measurement of the NT-proBNP level in the period before cardiac
      surgery can indicate the postoperative prognosis of the patient and may be a
      predictor of the need for postoperative inotropic treatment.

PMID- 17186983
TI  - Aortic stenosis severity is not a risk factor for poststenotic dilatation of the
      ascending aorta.
AB  - BACKGROUND: Dilatation of the ascending aorta in aortic stenosis may be partly
      explained by intrinsic wall structure changes, but the relative contribution of
      altered hemodynamics is unclear. The aim of this study was to assess the
      association between ascending aortic dimensions and valve stenosis severity.
      METHODS AND RESULTS: An analysis of echocardiographic examinations was conducted
      in 296 patients with aortic stenosis (179 males, mean age 71 years), 57 with
      bicuspid and 239 with tricuspid aortic valve, mean transaortic gradient 43+/-20
      mmHg, and not more than moderate aortic regurgitation. Aortic dimensions at the
      level of annulus, sinuses of Valsalva, sinotubular junction and proximal
      ascending aorta were measured. Only height (p<0.001), degree of aortic
      regurgitation (p<0.01) and presence of bicuspid aortic valve (p<0.001) were
      independent predictors of ascending aortic dimensions. CONCLUSIONS: An
      independent association between aortic pressure gradients and proximal ascending
      aortic dimensions was not observed in patients with bicuspid or tricuspid aortic
      valve stenosis. Therefore, the poststenotic dilatation of the ascending aorta is
      not explained by aortic stenosis severity itself. Possible nonhemodynamic causes
      deserve detailed study at the time of diagnosis.

PMID- 17186984
TI  - Clinical significance and reproducibility of new arterial distensibility index.
AB  - BACKGROUND: The brachial-ankle pulse wave velocity (baPWV) is used to evaluate
      the degree of atherosclerosis and arterial distensibility, but its major
      limitation is that it is affected by changes in blood pressure (BP) during
      measurement. Recently, a new atherosclerotic index, the cardio-ankle vascular
      index (CAVI), has been developed by measuring PWV and BP. CAVI is adjusted for BP
      based on the stiffness parameter beta and should measure arterial stiffness
      independent of BP. The purpose of this study was to evaluate the validity of CAVI
      compared with baPWV, the reproducibility of the measurement of CAVI, and the
      effect of BP changes on CAVI and baPWV. METHODS AND RESULTS: One thousand and
      thirty-three consecutive subjects undergoing health checkups were studied. CAVI
      was automatically calculated from the pulse volume record, BP, and the vascular
      length from heart to ankle. In this general population, both baPWV and CAVI
      demonstrated a positive correlation with age and systolic BP (SBP). CAVI showed a
      weaker correlation with SBP than baPWV. The measurement of CAVI demonstrated good
      reproducibility and was not affected by the increase in BP during measurement.
      CONCLUSIONS: CAVI is a useful index of arterial distensibility and is not
      influenced by BP changes during measurement.

PMID- 17186985
TI  - Evaluation of medical treatment for peripheral arterial disease in Chinese high
      risk patients.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is an important manifestation of
      systemic atherosclerosis and is associated with elevated cardiovascular morbidity
      and mortality. The aim of the present study was to evaluate the use of
      antiplatelet agents, statins and angiotensin-converting enzyme inhibitors (ACEI)
      in Chinese high-risk cardiovascular (CV) patients with PAD, with an emphasis on
      the need for aggressive medical management of all atherosclerotic manifestations.
      METHODS AND RESULTS: Medical records from 5,263 Chinese patients at high risk of
      CV were evaluated for the use of antiplatelet agents, statins and ACEI in
      patients with and without PAD. PAD was defined as an ankle-brachial index
      (ABI)<0.9 in either leg. Multivariable logistic regression analyses were
      performed to compare medication use in the 2 groups. A total of 5,254 patients
      were analyzed (52.9% male, mean age 67.3 years). The prevalence of PAD in the
      total patient group was 25.4%; 22.5% of them had PAD only. Overall, 5.7% had PAD
      only, 19.6% had PAD and coronary heart disease (CHD) or stroke or diabetes, 7.7%
      had CHD only, 12.6% had stroke only, and 13.6% had diabetes only. The 28.9%
      subjects having none of PAD, CHD, stroke or diabetes were used as the reference
      group. Only 65%, 37% and 47% of all patients received antiplatelet agents,
      statins and ACEI, respectively. Antiplatelets, statins, ACEI and all 3
      medications were used less frequently in PAD only patients (58.1%, 35.9, 53.5%
      and 21.6%) vs CHD only (90.9%, 74.5%, 70.6% and 55.9%, p<0.001). All 3 proven
      efficacious therapies were prescribed for only 56% of patients with CHD only, 8%
      with stroke only, 13% with diabetes only and 21% with PAD only. CONCLUSION: PAD
      is prevalent in Chinese high-risk CV patients, equivalent to CHD, but these
      patients receive less intensive treatment than those with CHD. Programs to
      improve CV risk reduction in these high-risk patients are needed.

PMID- 17186986
TI  - Serum levels of S-glutathionylated proteins as a risk-marker for arteriosclerosis
      obliterans.
AB  - BACKGROUND: Oxidative stress plays a role in the development of chronic
      peripheral arterial disease (PAD) because under these conditions redox regulation
      is impaired, inducing the S-glutathionylation of proteins. A method of estimating
      the levels of S-glutathionylated proteins has been developed using biotinylated
      glutathione S-transferase, which allows the study of their crucial role in the
      oxidative stress-related progression of PAD. METHODS AND RESULTS: The serum
      levels of S-glutathionylated proteins were examined in 41 patients with
      arteriosclerosis obliterans (ASO) and 38 age-matched non-ASO patients using
      biotinylated glutathione S-transferase. The levels were higher in the patients
      with ASO, even early on, and positively correlated with the ankle/brachial index.
      In vitro, the levels of S-glutathionylated proteins were reduced in the presence
      of glutathione and glutaredoxin. CONCLUSIONS: Serum levels of S-glutathionylated
      proteins are a sensitive risk-marker for ASO at an early stage.

PMID- 17186987
TI  - Impact of chronotropic effect of cilostazol after acute myocardial infarction:
      insights from change in left ventricular volume and function.
AB  - BACKGROUND: Cilostazol, a phosphodiesterase inhibitor, is an antiplatelet agent
      with positive chronotropic effect, the impact of which on left ventricular (LV)
      volume and function in acute myocardial infarction (AMI) was evaluated in the
      present study. METHODS AND RESULTS: In 56 patients with AMI treated with primary
      coronary stenting, serial echocardiographic studies within 24 h and at 6 months
      were performed. Patients received a conventional antiplatelet regimen either
      without cilostazol (group 1, n=29) or with cilostazol (group 2, n=27). At 6
      months, the difference in the change in heart rate between group 1 and group 2
      was statistically significant (9.9 beats/min; p=0.04). However, changes in LV end
      systolic volume (LVESV) (7.1+/-8.2 vs 10.0+/-21.7 ml, p=0.60), LV ejection
      fraction (EF) (8.2+/-9.9 vs 9.0+/-12.6%, p=0.85) and the ratio of early mitral
      inflow velocity to the mitral annular velocity (E/E') (0.6+/-3.7 vs -1.7+/-3.2)
      were not different between the 2 groups. Cardiac event rate was similar between
      the 2 groups. On multivariate regression analyses, cilostazol therapy had no
      significant influence on the changes in LVESV, LVEF or E/E'. CONCLUSIONS: In this
      study, the addition of cilostazol on conventional drug therapy had no adverse
      influence on LV remodeling or LV function after AMI.

PMID- 17186988
TI  - Multidetector-row computed tomography coronary angiography: optimization of image
      reconstruction phase according to the heart rate.
AB  - BACKGROUND: To optimize the image reconstruction phase of multidetector-row
      computed tomography (MDCT) coronary angiography according to the heart rate is
      crucial. METHODS AND RESULTS: Scan data were reconstructed for 10 different
      phases in 58 sequential patients who underwent 8-row cardiac MDCT. The obtained
      images were scored and compared in terms of motion artifacts and visibility of
      the vessels, and moreover, ECG record-based evaluations were added for
      clarification of the temporal relationships among these 10 phases. In the cases
      with lower heart rates (<65 beats/min), the best quality images were obtained
      when the end of the image reconstruction phase was positioned at the peak of the
      P wave. In some cases with higher heart rates (>65 beats/min), they were obtained
      in the late systolic period. CONCLUSION: As the heart rate increased, the optimal
      image reconstruction phase changed from mid diastole to late systole. However, it
      is recommended to try to decrease the heart rate of patients before data
      acquisition.

PMID- 17186989
TI  - Diagnosis of left atrial appendage thrombi by multiplane transesophageal
      echocardiography: interlaboratory comparative study.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) is regarded as the method of
      choice for imaging left atrial appendage thrombi (LAAT). However, the
      interobserver variability among 2 independent echocardiographic laboratories in
      diagnosing LAAT by multiplane TEE has not yet been assessed. METHODS AND RESULTS:
      The videorecordings of 50 patients in atrial fibrillation (25 from each
      laboratory) were blindly reviewed by 1 experienced observer from each
      institution. LAAT were assessed as present, absent or questionable. Indications
      for TEE were: cardioversion (n=17), valve disease (n=13), endocarditis (n=12), or
      embolism (n=8). The prevalence of LAAT was 10% (observer 1) vs 12% (observer 2).
      A questionable LAAT was assessed in 6% vs 12% and a LAAT was excluded in 84% vs
      76%, respectively. By head-to-head comparison, disagreement occurred in 11 cases
      (22%, kappa=0.5). Discrepant results were not related to the echocardiographic
      equipment. Problems occurred because of reverberation artifacts of the ridge
      between the left atrial appendage and left upper pulmonary vein (n=5), and in
      differentiating LAAT from spontaneous echocardiographic contrast (n=4) or an
      echogenic atrioventricular groove (n=1). The differentiation of pectinate muscles
      from LAAT was the reason for disagreement in only 1 case. Eliminating the
      category of questionable thrombi increased the kappa value to 0.65. In 5 patients
      undergoing cardiac surgery, both observers had agreed on the presence (n=1) or
      absence (n=4) of LAAT, and intraoperatively the results of TEE were confirmed.
      CONCLUSION: Even with multiplane TEE, interobserver variability among 2
      independent echocardiographic laboratories for diagnosing LAAT remains high
      because of problems in differentiating LAAT from spontaneous echocardiographic
      contrast and reverberation artifacts.

PMID- 17186990
TI  - Reverse perfusion-metabolism mismatch predicts good prognosis in patients
      undergoing cardiac resynchronization therapy: a pilot study.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) improves glucose metabolism
      in the septum of patients with heart failure, so in the present study the
      predictive value of combined fluorodeoxyglucose (FDG)-positron emission
      tomography (PET) and metoxy-isobutyl isonitrile (MIBI)-single photon emission
      computed tomography (SPECT) for the prognosis of patients undergoing CRT was
      investigated. METHODS AND RESULTS: Fourteen patients (70.3+/-8.2 years) who
      underwent FDG-PET and MIBI-SPECT before implantation of a biventricular pacemaker
      were enrolled. The total number of matches, mismatches, reverse mismatches,
      summed difference score (SDS: sum total of FDG - MIBI scores) and SDS per segment
      (%SDS) in each of 5 areas of myocardium (septum, anterior, lateral, inferior
      area, apex) was calculated and compared between the survival groups (all
      survival: survival group; survival without ischemic heart disease (IHD): non-IHD
      survival group) and non-survival group. Both the number of reverse mismatch
      segments and the %SDS in the septum in the non-IHD survival group were
      significantly greater than in the non-survival group (3.2+/-1.6 vs 0.5+/-0.6,
      p<0.05; 0.62+/-0.61 vs -0.11+/-0.19, p<0.05). The receiver-operating
      characteristics curves for prognosis showed that the area under the curve for the
      number of reverse mismatch segments in the septum (0.93; confidence interval 0.61
      0.98) was significantly greater. CONCLUSION: A reverse mismatch pattern in the
      septum can predict a good prognosis for patients treated with CRT.

PMID- 17186991
TI  - Sustained-release erythropoietin ameliorates cardiac function in infarcted rat
      heart without inducing polycythemia.
AB  - BACKGROUND: The usefulness of sustained-release erythropoietin for improving left
      ventricular (LV) function without polycythemia was evaluated in a rat chronic
      myocardial infarction model. METHODS AND RESULTS: Four weeks after left coronary
      artery ligation, 50 Sprague-Dawley rats were assigned to 5 groups (n=10, each).
      Control group had a gelatin sheet (20x20 mm) containing saline applied to the
      infarct area, whereas the 4 treatment groups had gelatin sheets incorporating
      erythropoietin 0.1 U, 1 U, 10 U and 100 U, respectively. Endpoint measurements
      performed at 8 weeks after the coronary ligation revealed that the fractional
      area change was larger for erythropoietin 1 U and 10 U than in the other 3
      groups. The LV end-systolic elastance and the time constant of isovolumic
      relaxation were better for erythropoietin 1 U and 10 U than in the other 3
      groups. The density of vessels larger than 50 microm in diameter was the highest
      in the erythropoietin 1 U group. The number of red blood cells was significantly
      increased in groups receiving erythropoietin 10 U and 100 U. CONCLUSIONS: Gelatin
      hydrogel sheets incorporating 1 U erythropoietin improved LV function without
      inducing polycythemia in a rat chronic myocardial infarction model.

PMID- 17186992
TI  - Granulocyte colony-stimulating factor prevents progression of monocrotaline
      induced pulmonary arterial hypertension in rats.
AB  - BACKGROUND: Regeneration of the lung microvasculature and replacing pulmonary
      artery lesions with functional endothelial cells could be a novel and effective
      therapeutic strategy for treating advanced pulmonary arterial hypertension (PAH).
      In the present study it was postulated that granulocyte colony-stimulating factor
      (G-CFS), which induces the proliferation of endothelial cells, would stimulate
      endothelial regeneration in situ at sites of impaired lung vasculature and
      prevent the development of PAH. METHODS AND RESULTS: Daily administration of G
      CSF for 48 days did not affect the hemodynamism of normal Fischer 344 rats. PAH
      was induced with monocrotaline (60 mg/kg) and G-CSF was administered daily (100
      microg/kg per day). Echocardiographic findings and an invasive catheter study
      indicated a significant decrease in the progression of PAH in rats given G-CSF.
      Furthermore, G-CSF increased Ki-67 positivity in the pulmonary arteries of PAH
      rats but did not accelerate c-kit positive cell recruitment into peripheral
      blood. Daily doses of G-CSF at both 2 and 100 microg/kg improved the survival and
      body weight gain of PAH rats. CONCLUSIONS: G-CSF improved the progression of PAH
      in a rat model, possibly by stimulating pulmonary endothelial cells to
      proliferate at sites of impaired lung vasculature. These findings show that
      cytokine therapy for PAH is valid based on the concept of vascular regeneration.

PMID- 17186993
TI  - Differential impact of atorvastatin vs pravastatin on progressive insulin
      resistance and left ventricular diastolic dysfunction in a rat model of type II
      diabetes.
AB  - BACKGROUND: Controversy exists regarding the effects of statin therapy on
      progressive insulin resistance (IR) and its consequences, in the present study a
      rat model of spontaneously developing type II diabetes mellitus (DM) was used to
      examine the impact of atorvastatin (AS) vs pravastatin (PS). METHODS AND RESULTS:
      The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with
      100 mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much
      greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new
      onset diabetes was delayed by PS only. The untreated rats exhibited a progressive
      decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis
      factor-alpha, and reduction of plasma nitric oxide (NO), which were limited more
      by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white
      adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was
      upregulated, and overexpression of both transforming growth factor-beta1 and
      monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary
      perivascular fibrosis at 30 weeks was suppressed only by PS, which was
      accompanied by preserved left ventricular diastolic function assessed with
      Doppler echocardiography. CONCLUSIONS: The moderate lipid lowering by PS, but not
      the intensive lipid lowering by AS, prevented new-onset DM and diastolic
      dysfunction in a rat model of IR, and this was associated with preferable
      adipocytokine profiles and cardiac redox states.

PMID- 17186994
TI  - Heart preservation using continuous ex vivo perfusion improves viability and
      functional recovery.
AB  - BACKGROUND: Cold static storage (CS) is a proven preservation method for heart
      transplantion, yet early postoperative graft dysfunction remains prevalent, so
      continuous perfusion (CP) during ex vivo transport may improve viability and
      function of heart grafts. METHODS AND RESULTS: Canine hearts underwent CP (n=9)
      or CS (n=9) for 6 h while intramyocardial pH was continuously monitored. Biopsies
      were assayed for ATP, caspase-3, malondialdehyde (MDA), and endothelin-1 (ET-1)
      levels at baseline, after preservation (t1), and after 1 h of blood reperfusion
      on a Langendorff model (t2). Functional recovery was determined at t2 by +dP/dt, 
      dP/dt, developed pressure, peak pressure and end-diastolic pressure. CP resulted
      in higher tissue pH and ATP stores and reduced caspase-3, MDA and ET-1 levels
      compared with CS at both t1 and t2. Post reperfusion recovery was significantly
      greater in CP vs CS for all myocardial functional parameters except end-diastolic
      pressure. Weight gain was significantly increased in CP vs CS at t1, but not at
      t2. CONCLUSIONS: Low-grade tissue acidosis and energy depletion occur during CS
      and are associated with oxidative injury and apoptosis during reperfusion. CP
      attenuates these biochemical and pathologic manifestations of tissue injury,
      together with improved myocardial recovery, despite mild, transient edema.

PMID- 17186995
TI  - Atrial tachycardia arising from the right atrial inferoseptum masquerading as
      common atrial flutter.
AB  - Radiofrequency catheter ablation was performed in 2 patients with atrial
      tachycardia (AT). In both cases the AT originated from the inferoseptal portion
      of the right atrium, and the cycle length was 210 ms. The surface ECG
      demonstrated common counterclockwise atrial flutter, probably caused by
      functional block in the clockwise direction at the cavo-tricuspid isthmus and
      posterior right atrium with rapid activation of the origin. Although rare (2%),
      AT originating from the inferoseptum of the right atrium should be considered
      when the surface ECG exhibits common atrial flutter.

PMID- 17186996
TI  - Cluster differentiation-36 deficiency type 1 and acute coronary syndrome without
      major cardiovascular risk factors: case report.
AB  - A 45-year-old man without major coronary risk factors, including hypertension,
      diabetes mellitus, smoking, hypercholesterolemia, hyperuricemia, or a family
      history of early cardiovascular disease, presented with acute coronary syndrome.
      Angiography showed thrombus formation in segment 7 of the left anterior
      descending coronary artery, and percutaneous coronary intervention was successful
      after implantation of a bare metal stent. Scintigraphy showed the absence of 123I
      beta-methyl-iodophenyl pentadecanoic acid accumulation in the myocardium. Flow
      cytometric analysis of platelets and monocytes showed the absence of cluster
      differentiation (CD)-36 expression. These findings are consistent with a
      diagnosis of CD36 deficiency type 1, which might be associated with
      cardiovascular disease. The patient had no apparent major coronary risk factors
      except for insulin resistance and an abnormal lipoprotein profile. The findings
      suggest that in this case the CD36 deficiency type 1 was the pathogenic mechanism
      of acute coronary syndrome relative to insulin resistance and modification of the
      lipid profile.

PMID- 17186997
TI  - Melatonin and lipid uptake by murine fibroblasts: clinical implications.
AB  - The current study was undertaken to uncover the role of melatonin in lipid
      metabolism in the murine fibroblasts. The results show melatonin in vitro
      enhances lipid accumulation and lipid droplet formation in this cell line. Using
      oil red O staining, it was found that when oleic acid was present in the culture
      media, melatonin at doses of 0.1-2mM, significantly increased the lipid
      concentrations in the cells. However, low levels of melatonin, with or without
      oleic acid, did not influence lipid metabolism in the cultured fibroblasts. When
      a non-specific melatonin receptor antagonist, luzindole 10 microM was co
      incubated with 1mM melatonin, the stimulatory effects of melatonin on lipid
      accumulation in these cells was significantly reduced. It appears that the
      effects of melatonin on lipid metabolism in murine fibroblasts is mediated by
      melatonin membrane receptors.

PMID- 17186998
TI  - Cortisol titre increases with novelty of academic oral examinations.
AB  - OBJECTIVE: In the present study we evaluated whether intensity and novelty of
      oral academic examinations are reflected in saliva cortisol titre. DESIGN AND
      SETTING: 91 pupils completed questionnaires on sensation seeking according to
      Zuckerman as well as on stress coping strategies and rated their individual
      stress intensity upon minor oral examinations. 26 of these students donated
      saliva samples before as well as ten and 30 minutes after the examination to
      quantify cortisol using an immuno assay. Oral examinations during the school
      year, where students may re-adjust their grade on subsequent examinations, were
      regarded as minor oral examinations, whereas school exit examinations, where
      students do not have the chance to correct their grade anymore and may even risk
      a delay of several months in their academic career when they fail, were regarded
      as major examinations. RESULTS: Minor oral examinations revealed either a
      moderate, but significant, increase in saliva cortisol titre by 1.1 fold or did
      not have a significant impact on cortisol titre. In contrast, school exit exams
      elevated cortisol titre 5.2 fold. In minor oral examinations, moderate
      correlations between cortisol titre and subsets in sensation seeking and coping
      strategies, respectively, were identified. CONCLUSION: Intensity and novelty of
      an academic examination is significantly correlated to cortisol titre. Minor oral
      examinations, with little consequences on academic career, only have a minor
      impact on cortisol titre, whereas school exit examinations, which are novel to
      students and may have major consequences on the academic career, elicit a major
      increase in cortisol titre.

PMID- 17186999
TI  - Serum sex hormones in premenopausal women with coronary heart disease.
AB  - OBJECTIVES: The objectives of this study were to investigate the relationship
      between the incidence of coronary heart diseases in premenopausal women and
      plasma level of total and free testosterone, estrogen, androstenedione and sex
      hormone binding globulin with coronary risk factors: fasting plasma concentration
      of glucose, triglyceride, total cholesterol, high and low density lipoproteins.
      METHODS: The study was conducted in Faculty of Medicine, Jordanian University of
      Science/Irbid Jordan and Technology and department of cardiology in Queen Alia
      Heart Institute/Amman Jordan during the period from April 2003 to March 2004.
      Serum sex hormones levels were measured in fifty-three premenopausal women; 25
      women with coronary heart disease who had hypertension and/or diabetes mellitus
      and 28 women without coronary heart disease. Ages ranged from 34 to 48 years.
      Blood samples were collected just before performing coronary angiography and
      serum was obtained and frozen at -70 degrees C until use. RESULTS: We found that
      the mean triglyceride, fasting blood sugar total cholesterol, and low density
      lipoprotein concentration were significantly higher in coronary heart disease
      patients than in patients with normal coronaries. We also found that the low
      levels of sex hormone binding globulin and high levels of free testosterone are
      associated with development of coronary heart disease. No significant correlation
      could be established between other plasma sex hormones level and coronary heart
      disease. CONCLUSION: In young women, in the presence of coronary risk factors and
      normal level of serum estrogen, the high levels of serum free testosterone and
      low levels of serum sex hormone binding globulin are associated with development
      of atherosclerosis and increased incidence of coronary heart disease.

PMID- 17187000
TI  - Cerebellar and thalamic metabolic changes visualized by [18]-FDG-PET in
      olanzapine-induced acute akathisia.
AB  - OBJECTIVES: Akathisia is a clinical important symptom, frequently induced by
      neuroleptic treatment. Despite its clinical importance, less is known about its
      pathophysiology. METHODS: Using [18]-FDG-PET, imaging patterns of cortical
      metabolic activity were obtained in a patient during olanzapine-induced akathisia
      and after recovery. RESULTS: Akathisia was characterized by a reduced metabolic
      activity in thalamus and cerebellum. After discontinuing medication akathisia
      disappeared, reflected by a recovery of metabolic activity in these brain areas.
      CONCLUSION: [18]-FDG-PET may be useful to identify cortical regions mediating
      clinical aspects of drug-induced akathisia, thereby offering a deeper insight
      into the pathophysiology of this serious side effect.

PMID- 17187001
TI  - Polymorphisms and low plasma activity of dopamine-beta-hydroxylase in ADHD
      children.
AB  - Attention-deficit Hyperactivity disorder (ADHD) is a multifactorial disorder
      clinically characterized by inattentiveness, impulsivity and hyperactivity. The
      occurrence of this disorder is between 3 and 6% of the children population, with
      boys predominating over girls at a ratio of 3:1 or more. The research of some
      candidate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought consistent
      results confirming the heredity of ADHD syndromes. Dopamine-beta-hydroxylase
      (DBH) is an enzyme responsible for the conversion of dopamine into noradrenaline.
      Alteration of the dopamine/noradrenaline levels can result in hyperactivity. The
      DBH protein is released in response to stimulation. DBH activity, derived largely
      from sympathetic nerves, can be measured in human plasma. Patients with ADHD
      showed decreased activities of DBH in serum and urine. Low DBH levels correlate
      indirectly with the seriousness of the hyperkinetic syndrome in children [19,20].
      In the DBH gene, the G444A, G910T, C1603T, C1912T, C-1021T, 5 -ins/del and TaqI
      polymorphisms occur frequently and may affect the function of gene products or
      modify gene expression and thus influence the progression of ADHD. This article
      reviews the DBH itself and polymorphisms in the DBH gene that influence the DBH
      activity in the serum and the CSF level of DBH. All those are evaluated in
      connection with ADHD.

PMID- 17187002
TI  - FSH-producing macroadenoma associated in a patient with Cushing's disease.
AB  - OBJECTIVE AND IMPORTANCE: We encountered a Cushing's disease patient whose
      surgically removed pituitary macroadenoma was not an ACTH-producing, but rather a
      gonadotroph adenoma. Cure was obtained only after a tiny microadenoma, overlooked
      on preoperative studies, was removed by a 2nd operation from a compressed thin
      normal anterior pituitary gland. CLINICAL PRESENTATION: This 45-year-old woman
      with Cushing syndrome presented with diabetes mellitus and steroid psychosis.
      Endocrinological examinations suggested Cushing's disease and MRI disclosed an
      invasive macroadenoma (22 mm in diameter) with suprasellar extension.
      INTERVENTION: Despite total removal of the invasive macroadenoma by
      transsphenoidal surgery, her elevated serum cortisol- and ACTH levels failed to
      decrease. Histologic study of the surgical specimen disclosed that the tumor was
      a silent FSH-producing, rather than an ACTH-producing adenoma. Detailed re
      evaluation of pre- and postoperative MRI suggested the presence of a 3-mm
      microadenoma on the left side of a thin compressed normal gland. Venous sampling
      of the cavernous sinus confirmed this suspicion. In a 2nd operation an ACTH
      producing microadenoma was removed from inside the thin remaining compressed
      normal pituitary gland and endocrinological cure of Cushing's disease was
      achieved. CONCLUSION: Although double adenomas, being a non-ACTH producing
      macroadenoma associated with an ACTH producing tiny microadenoma, are extremely
      rare in patients with Cushing's disease, detailed preoperative MRI evaluation is
      necessary to avoid missing tiny adenomas hidden in a compressed normal pituitary
      gland which is the cause of Cushing's disease, especially when a macroadenoma is
      found in patient with Cushing's disease.

PMID- 17187003
TI  - Lower omega-3 polyunsaturated fatty acids and lower docosahexaenoic acid in men
      with pedophilia.
AB  - BACKGROUND: Previous studies have suggested that abnormalities in plasma
      phospholipid fatty acids may play a role in aggressive behavior. Recently, it was
      suggested that a dysfunctional serotonergic turnover in the brain may be involved
      in the etiopathology of pedophilia. Depletion of n-3 polyunsaturated fatty acids
      (PUFA) may cause alterations in the serotonergic system that may be related to
      pedophilia and aggression. METHODS: This study examines the serum phospholipid n
      3 and n-6 PUFA fractions in pedophilia. Twenty-seven pedophilic men and eighteen
      healthy volunteers participated in this study. RESULTS: In pedophilia there was a
      significant depletion of the C22:6n-3 (docosahexaenoic acid, DHA), total n-3
      fractions and an increase in the total n-6/n-3 and C20:4n-6/C20:5n-3 (arachidonic
      acid/eicosapentaenoic acid) ratios. Using the NEO Personality Inventory, lower
      DHA in pedophiles is related to more impulsiveness and lower agreeableness
      (trust, altruism, straightforwardness, compliance) and conscientiousness (self
      discipline). CONCLUSIONS: The results of this study suggest that a depletion of
      the serum phospholipid n-3 higher unsaturated fatty acids (HUFAs) and, in
      particular, of DHA may take part in the pathophysiology of pedophilia. One
      hypothesis is that a depletion of n-3 HUFAs and DHA may cause alterations in the
      serotonergic turnover, which are related to impulse discontrol and aggression
      hostility, behaviors which are associated with pedophilia.

PMID- 17187004
TI  - Increased alpha-subunit response coexist with increased TSH response to TRH test
      in healthy individuals.
AB  - OBJECTIVE: The alpha-subunit (Alpha-SU) response to TRH was studied to examine
      the response of alpha-SU under TRH stimulation in normal situation. METHODS:
      Thirty seven healthy individuals were included in the study. They were divided
      into two groups according to the data taken: A with TSH equal or more than seven
      fold the basal values (0: 3.14+/-1.2 microU/ml., 30 after TRH: 20.22+/-4.6
      microU/ml) and B with TSH 2 to 6 fold the basal values (0: 0.5+/-0.1 microU/ml.,
      30 after TRH: 2.9+/-0.5 microU/ml). Both groups exhibited similar FT3 and FT4
      levels. RESULTS: In group A, prolactin displayed a 3 fold increase from the basal
      values, whereas alpha-SU increased 4 fold with a difference being statistically
      significant (p<0.001). In contrast, in group B individuals neither prolactin nor
      alpha-SU exhibited any significant difference from the basal values. CONCLUSION:
      The expression of alpha-SU upon TRH stimulation is dependent on the TSH basal
      values.

PMID- 17187005
TI  - Plasma ghrelin concentrations in patients with polycystic ovary syndrome before
      and after 6months therapy: correlation with androgen levels.
AB  - OBJECTIVE: Ghrelin is a natural ligand of the growth hormone secretagogue
      receptor and has been shown to be a potent stimulant of GH secretion. It has also
      orexigenic effects and regulates energy homeostasis. Recent studies claim that
      ghrelin influences the androgen level and probably takes part in PCOS
      pathomechanism. The aim of the study was an assessment of ghrelin level in plasma
      in women with PCOS before and after the treatment and ghrelin's influence on
      androgen level change. MATERIAL AND METHODS: The study included 25 women with the
      diagnosed PCOS (mean age 25.3+/-4.05 yr). The tests were done twice: before the
      treatment and after 6-month therapy with Diane 35 (cyproterone acetate 2 mg with
      ethinylestradiol 35 mug). Following hormones were measured: ghrelin, free
      testosterone, androstendione, dehydroepiandrosterone sulfate, 17-OH-progesterone
      and estradiol. RESULTS: The received results in both groups were compared with
      the control group (11 healthy women, mean age 26.0+/-2.6 yr). No statistically
      significant differences in ghrelin levels before (187.8+/-8.1 fmol/ml) and after
      the therapy (185.6+/-9.5 fmol/ml) were found. Similar results were received when
      two groups of women compared with the control (186.5+/-8.7 fmol/ml). No
      correlations between ghrelin and androgen levels were confirmed. CONCLUSIONS:
      Final conclusion is that there is no direct impact of ghrelin level on PCOS
      pathogenesis, however, its role in development of obesity, hyperinsulinemia and
      insulin resistance co-occurring with metabolic disorders syndrome cannot be
      excluded.

PMID- 17187006
TI  - Low-dose risperidone augmentation of antidepressants or anxiolytics is associated
      with hyperprolactinemia.
AB  - OBJECTIVE: Risperidone in antipsychotic doses induces hyperprolactinemia. The aim
      of this study was to verify whether the same is true for low doses of risperidone
      (0.5-2 mg per day) added to antidepressants or anxiolytics. METHODS: Prolactin
      levels were measured in 4 men (mean age 49.5+/-19.1 years) and 8 women (mean age
      31.3+/-8.2 years) inpatients with depressive and anxiety disorders who were
      treated with risperidone (median doses per day 1.25 mg) for median 15.5 days as
      an augmentation treatment to antidepressants (n=8), anxiolytics (n=6) and mood
      stabilizers (n=2). RESULTS: 11 of 12 patients had hyperprolactinemia. Median
      plasma prolactin level was 1598 mIU/ml, 95% CI 1 040-2 661 mIU/ml. Significant
      correlation between risperidone daily dose and plasma prolactin level (Spearman's
      R=0.655, p=0.02) was detected. Two women suffered from galactorrhea and one from
      amenorrhea. CONCLUSIONS: Even low doses of risperidone used as an augmentation to
      antidepressants or benzodiazepines are associated with hyperprolactinemia and can
      induce endocrinological side effects. The co-medication of antidepressants and
      benzodiazepines can potentially increase intensity of prolactinemia.

PMID- 17187007
TI  - The metallothionein and RCAS1 expression analysis in breast cancer and adjacent
      tissue regarding the immune cells presence and their activity.
AB  - INTRODUCTION: The generation of proper immune response in the tumor environment
      seems to be essential in antitumor defense. RCAS1 expression has been shown to
      participate in the regulation of immune cytotoxic activity, metallothionein
      participates in the protection of cells against immune mediated apoptosis. Since
      MT and RCAS1 expression is observed within healthy tumor environment we aimed to
      focus on the proteins expression in tumor and its healthy adjacent tissue in
      invasive ductal breast cancer regarding the immune cells presence and activity.
      MATERIAL AND METHODS: RCAS1, metallothionein, CD3, CD56, CD4, CD25, CD69, CD68
      and CD16 antigens expression was assessed by immunohistochemistry in invasive
      ductal breast cancer. Tissue samples were obtained from 45 patients and were
      grouped according to the presence of lymph nodes metastases. Two groups were
      obtained: with and without lymph nodes metastases. RESULTS: Significant
      differences were observed in RCAS1 and metallothionein expression in tumor and
      significant differences in metallothionein expression in healthy stroma regarding
      the presence of lymph nodes metastases. The significantly higher RCAS1 expression
      was noticed in tumor in comparison to stroma in patients with the presence of
      lymph nodes metastases. No such difference was observed in patients without the
      metastases. Significantly higher metallothionein expression was identified in
      tumor than in stroma in both groups of patients, with and without lymph nodes
      metastases. These changes in RCAS1 and metallothionein expression were
      significantly related with the changes in the number and activity of immune
      cells. CONCLUSION: RCAS1 and metallothionein expression in breast cancer healthy
      stroma seems to be essential for the coexistence of cytotoxic immune cells and
      normal epithelial cells. The loss of the ability to compensate the growing
      cytotoxic immune response in the environment might participate in the development
      of tumor spread.

PMID- 17187008
TI  - The characterization of the exposure to immune mediated apoptosis and the
      regulation of immune cytotoxic activity in the environment of a neoplasm and in
      decidua.
AB  - Acquiring the immune-mediated apoptosis and the ability to regulate the cytotoxic
      immune response are the main phenomena playing fundamental roles in such
      situations as neoplasm survival and creation of immune tolerance during
      pregnancy. The aim of this study was to investigate these phenomena through the
      evaluation of metallothionein and RCAS1 proteins in neoplasm and its healthy
      environment (clear surgical margin), physiological conditions in placenta and its
      environment (decidua) and the comparison to non-neoplasmatic lesions originating
      from the environment (nasal polyps, endometriosis). We have shown that the growth
      of RCAS1 expression was simultaneous to the infiltration of activated
      immunological cells of tumor environment as well as decidua. The activity of
      immunological cells was in our study selectively suppressed. Metallothionein
      expression growth was also observed in healthy tumors stroma and in decidua
      probably in response to the growing cytotoxic activity and tumor spread.
      Alterations in RCAS1 and Metallothionein expression seem to be associated with
      local immune dysfunction in nasal polyps and endometriosis. In conclusion, the
      ability to compensate the growing cytotoxic immune response is physiologically
      observed in decidua, the lost of this ability in tumor environment might
      participate in the development of tumor spread.

PMID- 17187009
TI  - The COMT Val158Met polymorphism is associated with novelty seeking in Czech
      methamphetamine abusers: preliminary results.
AB  - OBJECTIVES: Measurable traits of human personality may mark the predisposition to
      psychopathology. Increased novelty seeking plays an important role in the
      pathogenesis of substance abuse. Novelty seeking, one of the fundamental traits
      of the human temperament, is related to dopamine. Catechol-O-methyltransferase
      (COMT) is essential for dopamine inactivation. The aim of our study was to assess
      whether the COMT gene Val158Met functional polymorphism in patients dependent on
      methamphetamine is related to their novelty seeking score. METHODS: Patients
      dependent on methamphetamine who had been treated at the Addiction Treatment Unit
      in Nechanice in 2004 and 2005 agreed to participate in the investigation. We
      administered the Temperament and Character Inventory (TCI) questionnaire,
      assessed their novelty seeking score and analysed their DNA samples for COMT
      Val158Met genotype. RESULTS: The subjects were thirty-seven Czech Caucasians
      (women N=10) dependent on methamphetamine with an average age of 23.6+/-3.8
      years. We found a significantly higher mean novelty seeking score among the
      patients with the Met allele (Met/Met homozygotes+Val/Met heterozygotes; N=28)
      than in nine Val/Val homozygotes (27.4 vs 24.1; p=0.042, Two-Sample T-Test).
      CONCLUSION: The Met allele of the COMT gene Val158Met polymorphism is associated
      with low COMT enzyme activity and high endogenous dopamine synaptic levels in the
      prefrontal cortex. This leads to a decrease in dopaminergic neurotransmission in
      nucleus accumbens and a need for an increased activity to stimulate it. Novelty
      seeking behavior corresponds with this need.

PMID- 17187010
TI  - A clinical trial of combined anti-androgen and anti-heavy metal therapy in
      autistic disorders.
AB  - BACKGROUND: A medical hypothesis has suggested that some autism spectrum
      disorders (ASDs) may result from interactions between the methionine cycle
      transsulfuration and androgen pathways following exposure to mercury. METHODS:
      The IRB of the Institute for Chronic Illnesses approved the present study. A
      novel treatment was utilized combining LUPRON (leuprolide acetate, TAP
      Pharmaceuticals, Inc.) and CHEMET (meso-2, 3-dimercaptosuccinic acid--DMSA,
      McNeil Consumer Products Company) on 11 consecutive children with ASDs. RESULTS:
      A significant (p<0.01) overall improvement from the 70-79th percentile of
      severity (median baseline score=87) at baseline to the 40-49th percentile of
      severity (median end of study period score=63) at the end of the study was
      observed for patients treated for a median of approximately 4 months. Significant
      improvements in sociability, cognitive awareness, behavior, and clinical
      symptoms/behaviors of hyperandrogenemia were also observed. Significant decreases
      in blood androgens and increases in urinary heavy metal concentrations were
      observed. Minimal drug adverse effects were found. CONCLUSION: This study
      provides the first clinical evidence for the benefit that combined anti-androgen
      and anti-heavy metal therapy may have on some children with ASDs. Additional
      studies should examine androgen and heavy metal mechanisms of action in ASDs, and
      future ASD treatment protocols should consider androgens and heavy metals.

PMID- 17187011
TI  - Photodynamic therapy with Verteporfin in subfoveal choroidal metastasis of breast
      carcinoma (a controlled case).
AB  - A 55-year old woman with growing unilateral subfoveal choroidal metastasis of
      breast carcinoma was treated by photodynamic therapy (PDT) with verteporfin. Best
      corrected visual acuity remained stable during the whole follow-up of 6 months.
      Tumor flattened from 2.2 mm to 0 mm on ultrasound one month after the therapy.
      PDT with verteporfin appears to be the best tolerated method for palliative
      treatment of growing subfoveal choroidal metastasis of the breast carcinoma.

PMID- 17187012
TI  - Effects of testosterone on differentiation and oxidative stress resistance in
      C1300 neuroblastoma cells.
AB  - OBJECTIVES: Using undifferentiated mouse neuroblastoma cells (C1300), we have
      previously observed that testosterone (T) exerts a neuroprotective action against
      oxidative stress. Nitrogen intermediates induce the production of 3-nitro-L
      tyrosine (3NT), an amino acid analogue involved in many neurodegenerative
      disorders. The aim of our work is to investigate T capability on C1300 cell
      differentiation. It is also evaluated whether differentiation could mitigate the
      nitrosative effects of 3NT. METHODS: The effects of both T and 3NT were studied
      on an undifferentiated cell line of neural origin (C1300). For this purpose, cell
      cultures underwent morphometric investigation, blot analyses and catalase
      activity assay. All data obtained were expressed as mean+/-SD and tested by one
      way ANOVA or Student's t test. RESULTS: The results were compared with those
      gathered by means of N6,2'-O-dibutyryl-adenosine-3',5'-cyclic-mono-phosphate (db
      cAMP), a well-known differentiating agent. T-exposed cells showed an irregular
      shape and exhibited long branching cytoplasmic extensions, which were longer than
      in db-cAMP cells. Moreover, T-exposure induced an increase in the expression of
      tyrosinated and acetylated alpha-tubulin while 3NT-incorporation into tubulin was
      markedly reduced. The action of antioxidant defence systems, namely catalase
      activity, was enhanced in cells exposed to T. CONCLUSION: This work highlighted
      the effects of db-cAMP on differentiation and neuroprotection, but even indicated
      that T exposure induced differentiation in C1300 cells and this process matches a
      significant neuroprotective effect. This action seemed to be more effective than
      in db-cAMP-treated cells. T is suggested, like other substances having
      antioxidant properties, to be of potential interest in the experimental therapy
      of neuropathological conditions.

PMID- 17187013
TI  - Butyrate sensitizes the release of substance P and calcitonin gene-related
      peptide evoked by capsaicin from primary cultured rat dorsal root ganglion
      neurons.
AB  - OBJECTIVES: To investigate whether butyrate increases substance P (SP) and
      calcitonin gene-related peptide (CGRP) release evoked by capsaicin from primary
      cultured dorsal root ganglion (DRG) neurons. METHODS: DRG was dissected out from
      embryonic 15-day-old Wistar rat and cultured as dissociate cells for 24 h then
      exposed to butyrate (0.01 mmol/L, 0.1 mmol/L, 1 mmol/L, 10 mmol/L, respectively)
      for another 48 h. The neurons cultured continuously in media served as normal
      control. All above cultured samples were processed for detecting expression of
      mRNA for SP, CGRP and vanilloid receptor 1 (VR1) of DRG neurons by RT-PCR, and
      VR1 protein expression by Western blot. SP and CGRP basal release levels were
      measured by radioimmunoassay (RIA). After that, the DRG cells for RIA were
      stimulated by capsaicin (300 nmol/L) for 5 min and the culture media were
      harvested for detecting SP and CGRP release levels by RIA. The neurons exposed to
      vehicle solution served as vehicle controls. RESULTS: Exposure of butyrate on DRG
      neurons at higher concentrations (1 mmol/L, 10 mmol/L) for 48 h increased
      expression mRNA for SP and CGRP than that at lower concentrations (0.01 mmol/L,
      0.1 mmol/L) and normal control (P<0.001). VR1 mRNA and VR1 protein expression
      increased in a dose-dependent manner after exposure of different concentrations
      of butyrate. Butyrate did not alter the basal release, significantly enhanced
      neuropeptide release evoked by capsaicin. SP and CGRP release levels in the
      culture media exposed by butyrate at higher concentrations (1 mmol/L, 10 mmol/L)
      for 48 h and then stimulated by capsaicin were higher than that at lower
      concentrations (0.01 mmol/L, 0.1 mmol/L) (P<0.001). The exposure of vehicle
      solution did not produce any increase of SP and CGRP release from primary
      cultured DRG neurons. DISCUSSION: Butyrate may promote the expression of mRNA for
      SP, CGRP and increase sensitivity of capsaicin on SP and CGRP release from
      primary cultured rat dorsal root ganglion neurons. The promotion of VR1 mRNA and
      VR1 protein expression by butyrate implicated that VR1 may be involved in the
      mechanisms of sensory neuropeptide release evoked by capsaicin.

PMID- 17187014
TI  - The usefulness of laparoscopy and hysteroscopy in the diagnostics and treatment
      of infertility.
AB  - OBJECTIVES: The aim of the study was to analyze the use of endoscopic procedures
      in the group of infertile patients. MATERIAL AND METHODS: The study material
      consisted of 636 patients, aged 20-41. They all had endoscopic procedures
      performed (laparoscopy and/or hysteroscopy) due to infertility, and were
      qualified for the procedure after a gynecological examination and ultrasound
      scan. The study group was divided into subgroups of primary and secondary
      sterility and endoscopic procedures were then analyzed. RESULTS: A total of 724
      endoscopic procedures were performed on 636 patients. Eighty eight women had both
      hysteroscopy and laparoscopy performed, 476 had only laparoscopy, while 72--only
      hysteroscopy. Women diagnosed due to primary sterility more often had no visible
      abnormalities in the pelvic region (30%) and patent oviducts than those with
      secondary sterility. The remaining 70% more often had ovaries typical for
      polycystic ovarian syndrome and endometriosis. However, periadnexal adhesions and
      tubal impotency were more common in the group of secondary sterility. As to
      hysteroscopy, women with primary sterility more often had congenital uterine
      malformations, while submucosal myomas and intrauterine adhesions were less
      common in that group. All the surgical procedures performed during laparoscopies
      were analyzed. Tubal patency assessment and ovarian drilling were significantly
      more often performed in the subgroup of primary sterility. All intrauterine
      pathologies were treated during hysteroscopy. CONCLUSIONS: Laparoscopy and
      hysteroscopy play an important role as both diagnostic and therapeutic tools in
      the infertility treatment centers.

PMID- 17187015
TI  - Laparoscopic management of dermoid cysts in patients of reproductive age.
AB  - OBJECTIVE: Ovarian dermoid cysts are one of the most common germ cell tumors in
      women. The aim of the study was to analyze the use of laparoscopy in dermoid
      cysts treatment in women of reproductive age. MATERIAL AND METHODS: The studied
      material consisted of 95 patients, aged 17-49, operated on because of dermoid
      cyst suspicion at the 1st Department of Obstetrics and Gynecology, Medical
      University of Warsaw, in the years 1996-2005. All the patients had pre-operative
      CA-125 antigen evaluation and transvaginal sonography with Doppler assessment of
      the ovarian pathology. All the women with tumors less than 8 cm in diameter were
      qualified for laparoscopic management. RESULTS: The majority of patients were
      below 40 years of age (86 women; 90.5%). Out of 95 studied cases, 93 (97.9%) had
      the cyst removed during laparoscopy, mostly elective. Dermoid cyst enucleation
      was the most commonly applied procedure, while oophorectomy was the least
      frequent. The whole gonad was removed in 33 patients (34.7%), generally because
      of the total loss of functional ovarian tissue surrounding the cyst (28 women;
      29.5%). All the extracted material was submitted for a histopathological
      examination--the diagnosis of mature ovarian cystic teratoma was confirmed in
      100% of cases. The correspondence of pre-operative sonographic imaging and
      intraoperative macroscopic assessment was evaluated. In 85 (89.5%) operated
      patients an ovarian tumor was earlier described as a dermoid cyst. CONCLUSIONS:
      Laparoscopic treatment of ovarian dermoid cysts is a safe method, offering many
      advantages in comparison to classical surgery. However, proper early
      qualification, based on medical history, gynecological and sonographic
      examination is of great importance.

PMID- 17187016
TI  - Clinical analysis of patients with pemphigoid-like ophthalmological symptoms.
AB  - PURPOSE: The aim of this study was a clinical analysis of patients with symptoms
      typical of pemphigoid. MATERIAL AND METHODS: 21 patients were enrolled on the
      study within the period 1988-2004. The frequency and type of ophthalmological and
      extraocular symptoms and accompanying diseases were assessed. The analysis also
      contains immunological findings as well as administered treatment. RESULTS:
      Ophthalmological changes were detected in 100% of examined patients with
      pemphigoid. The most frequent were dry eye syndrome and conjunctivitis.
      Immunohistochemical tests revealed the presence of antibodies in 68.2% of the
      examined cases. All patients required specific treatment--local, general and
      surgical. Despite the administered therapy the development of cicatricial changes
      was observed. CONCLUSIONS: Chronic conjunctivitis and keratitis require
      diagnostics into pemphigoid. Intensive therapy is necessary in patients with
      ocular cicatricial pemphigoid (OCP) because of high risk of blindness. Delayed
      diagnostics disable immunohistochemical confirmation of disease.

PMID- 17187017
TI  - Dominance, submissivity (and homosexuality) in general population: testing of
      evolutionary hypothesis of sadomasochism by Internet-trap-method.
AB  - OBJECTIVES: Dominance and submissiveness represent strong sexual arousal stimuli
      for a considerable part of population. In contrast to men's sexual dominance and
      women's sexual submissiveness, the opposite preferences represent an evolutionary
      enigma. Here, we studied prevalence and strength of particular preferences in
      general population by Internet-trap-method. DESIGN: The subjects who clicked the
      banner displayed in the web interface of e-mail boxes were allowed to choose
      icons with homosexual or heterosexual partner of different hierarchical position.
      RESULTS: Dominant partner was chosen by 13.8% men and 20.5% women, and submissive
      partner by 36.6% men and 19.8% women. Homosexual partners were chosen by 7.3% men
      and 12.2% women. The response times for the submissive and dominant stimuli did
      not differ while for the equal-status stimuli were significantly longer,
      suggesting that part of subjects with equal-status preferences probably
      intentionally mask their natural interests. CONCLUSIONS: Large number of people
      who chose unequal sexual partner suggests that hierarchical status plays
      important role in human mating system.

PMID- 17187018
TI  - Cord blood IGF-1 and IGFBP-3 levels in asphyxiated term newborns.
AB  - OBJECTIVE: Determination and pathogenesis of perinatal asphyxia is still an
      important problem. During the asphyxial insult and recovery phase, alteration of
      the growth factors has been demonstrated and there is evidence that expression of
      insulin-like growth factors (IGF) and their insulin-like growth factor binding
      proteins (IGFBP) in injured sites in experimental studies. Aim of this study was
      to evaluate relationship between serum IGF-1, IGFBP-3 levels and perinatal
      asphyxia. PATIENTS AND METHODS: 18 term-newborn who defined as perinatal asphyxia
      and 12 term-healthy newborn were enrolled. Umbilical cord IGF-1 and IGFBP-3
      levels were detected and searched correlation with apgar scores and umbilical
      artery gas analysis as pH, pC02, pO2, base excess, HCO3, ctO2, SO2 and lactate
      levels. RESULTS: Cord blood IGF-1 and IGFBP-3 levels for asphyxiated newborns
      were lower than normal group (27.8+/-2.6 ng/ml, 55.1+/-2.8 ng/ml respectively,
      p<0.01 for IGF-1; 1107.7+/-320.4, 1682.5+/-364.1, p<0.001 for IGFBP-3). Cord
      blood IGF-1 levels were positively correlated with birth weight; first and 5th
      minute Apgar score, cord blood arterial pH, ABE, HCO3, SO2 levels. Cord blood
      IGFBP-3 levels were positively correlated with first and 5th minutes Apgar
      scores, cord blood arterial pH, pCO2, ABE, HCO3, sO2, and also negatively
      correlated with cord CO2 and cord lactate levels. CONCLUSION: Our study
      demonstrates that exposure to hypoxia and acidosis at birth strongly correlated
      with a fall in IGF-1 and IGFBP-3 levels in cord blood.

PMID- 17187019
TI  - Plasma nerve growth factor (NGF) and inflammatory cytokines (IL-6 and MCP-1) in
      young and adult subjects with Down syndrome: an interesting pathway.
AB  - OBJECTIVES: Down's syndrome (DS) is the most frequent chromosomal aberration in
      men and it is invariably associated with mental retardation. MATERIAL AND
      METHODS: Plasma levels of nerve growth factor (NGF), interleukin-6 (IL-6), and
      monocyte chemoattractant protein-1 (MCP-1) from non demented DS subjects of three
      different age-cohorts (2-14 years; 20-50 yrs; >60 yrs) and healthy controls were
      measured. No clinical and sub-clinical inflammation was apparent in DS patients.
      RESULTS: Plasma levels of NGF were higher in children, adult and old DS subjects
      than in controls. However, a significant age-related decrease of NGF levels was
      present in DS subjects. Serum levels of IL-6 and MCP-1 were also increased in DS
      children and adults, but not in older DS patients. CONCLUSIONS: High levels of
      circulating NGF might protect DS from clinical complications of atherosclerosis.
      However, the striking decrement of peripheral NGF levels with advancing age may
      predispose DS to clinical manifestation of dementia after adulthood.

PMID- 17187020
TI  - Effects of ghrelin on circulating neuropeptide Y levels in humans.
AB  - OBJECTIVE: Ghrelin is a 28 amino-acid peptide with a strong GH-releasing activity
      and a complex role in regulation of appetite, fuel utilization, body weight and
      composition. Neuropeptide Y (NPY) is a well-known stimulator of pathways
      favouring food intake and energy storage. Recently, studies in rodents suggested
      a possible mediation of ghrelin action by NPY. In contrast, until now no evidence
      of ghrelin-NPY interaction in humans has been provided. In the present study, we
      examined whether ghrelin influences NPY secretion in normal men. SUBJECTS AND
      DESIGN: Twelve healthy normal men (aged 24-35 years; body mass index (BMI) 22.3+/
      0.93 kg/m2) were tested twice at 08.00 AM on two different days, in random order
      at weekly intervals, after an overnight fast and rest in bed. An intravenous
      bolus of 1 microg/kg body weight ghrelin (esperimental test) or an equal amount
      of normal saline (control test) was injected at time 0. Blood was taken before
      and over 90 minutes after injections, and was used for the measurement of plasma
      NPY levels. RESULTS: Plasma levels of NPY slightly, but significantly rose in
      response to ghrelin, with a mean peak level at 15 min after injection, whereas no
      significant change was observed after saline administration. MAIN FINDING: Our
      results show a significant enhancement of plasma NPY levels under ghrelin
      stimulation. CONCLUSIONS: To our knowledge, this is the first demonstration of a
      ghrelin-NPY interaction in humans, which may suggest a possible mediation of
      ghrelin action by NPY in humans.

PMID- 17187021
TI  - Uveal melanoma in congenital ocular melanocytosis mimicking malignant
      transformation of the optic disc melanocytoma (a controlled case).
AB  - A case of a 57-year old woman with uveal melanoma of the posterior pole arising
      in the congenital ocular melanocytosis mimicking clinically malignant
      transformation of the optic disc melanocytoma is presented.

PMID- 17187022
TI  - Reduced hypothalamic gray matter in narcolepsy with cataplexy.
AB  - OBJECTIVES: Narcolepsy with cataplexy is associated with a loss of hypocretin.
      The question is, if there is an autoimmune or neurodegenerative process
      selectively killing the hypothalamic hypocretin-containing neurons or if these
      cells survive but fail to produce hypocretin. To support one of these hypothesis
      we aimed to detect structural changes in the hypothalamus of narcoletic patients.
      MATERIALS AND METHODS: Nineteen narcoleptic patients were compared to 16 healthy
      controls. We used voxel-based morphometry (VBM), an unbiased MRI morphometric
      method with a high sensitivity for subtle changes in gray and white matter
      volumes to investigate hypothalamic region in this condition. RESULTS: Classical
      MRI protocol revealed no structural abnormalities, but using VBM we found
      significant reduction in hypothalamic gray matter volumes between patients and
      controls. CONCLUSIONS: VBM showed hypothalamic gray matter loss in narcolepsy
      with cataplexy. This suggest that functional abnormalities of hypocretin neurons
      in narcolepsy are associated with structural changes of hypothalamus.

PMID- 17187023
TI  - A new mutation in WFS1 gene (C.1522-1523delTA, Y508fsX421) may be responsible for
      early appearance of clinical features of Wolfram syndrome and suicidal behaviour.
AB  - OBJECTIVE: Wolfram syndrome (WS) is an autosomal recessive disorder characterized
      by the association of juvenile-onset diabetes mellitus and optic atrophy. It is
      also known by the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic
      atrophy, and deafness). PATIENTS, METHODS AND RESULTS: We diagnosed Wolfram
      syndrome in 2 male siblings and determined a new mutation (c. 1522-1523delTA,
      Y508fsX421). Both affected siblings were homozygous, other family members were
      heterozygous. Dilated renal outflow tracts in the third decade, and
      neuropsychiatric disorders including bipolar disorder and neurosensorial deafness
      appear in the fourth decade in ordinary WS, whereas these features appeared in
      second decade in our patients. This mutation may be responsible for early
      appearance of dilated renal outflow tracts and multiple neurological
      abnormalities. Psychiatric disturbances such as suicide were reported at
      increased frequency in Wolfram patients and in heterozygous carriers. Suicidal
      behaviour occurred in our patients when they were yet 11 and 13 years old.
      Therefore, our findings may indicate that there may be a relationship between
      this WFS1 mutation and mood disorder such as suicidal behaviour. CONCLUSIONS: We
      determined a new mutation (c. 1522-1523delTA, Y508fsX421) in WS1 gene in 2
      siblings with Wolfram syndrome. This mutation may be responsible for early
      appearance of clinical features of Wolfram syndrome, and there may be a
      relationship between this mutation and suicidal behaviour.

PMID- 17187024
TI  - A follow-up of 130 patients with acromegaly in a single centre.
AB  - OBJECTIVES: Acromegaly is a rare disease with increased mortality rate. The aim
      was to present our centre experience in the diagnosis and treatment of a series
      of patients suffering from acromegaly. METHODS: 130 patients (55 men, 75 women)
      aged 19-84 years presenting with clinical and hormonal features of acromegaly,
      attending Department of Endocrinology and Out-patient Clinic between 1990 and
      2004 were studied. They were analyzed their GH and IGF-1 levels, CT and MRI
      scans, and they were administered medical therapy, neurosurgery and radiotherapy.
      RESULTS: We have observed 106 macro-, 16 microadenomas and 1 case of ectopic
      GHRH. 115 patients were operated, as cured were recognized 74 of them. Pituitary
      irradiation was applied to 11 patients, in 4 of them it did not cure the disease.
      Medical therapy was efficacious in 12% patients treated with bromocriptine, 73%
      with long-acting lanreotide and 58% with long-acting octreotide. In 7 patients
      other malignant neoplasm were detected. 11 patients died during the follow-up.
      CONCLUSIONS: There is possible underdiagnosis of acromegaly in our region,
      especially in males. We have observed better diagnostic opportunities in recent
      years when MRI was available. It was accompanied by better outcome of surgical
      and pharmacological treatment and better control of the complications of the
      disease.

PMID- 17187025
TI  - Impact of cannabinoid receptor ligands on behavioural sensitization to
      antiaggressive methamphetamine effects in the model of mouse agonistic behaviour.
AB  - OBJECTIVES: Psychostimulants and cannabinoids can elicit so called behavioural
      sensitization after repeated administration, a gradually increased behavioural
      response to a drug. This phenomenon if conditioned by previous pre-treatment with
      different drug is termed cross-sensitization. The present study was focused on a
      possible sensitisation to antiaggressive effect of methamphetamine and cross
      sensitization to this effect after repeated pre-treatment with cannabinoid CB1
      and CB2 receptor ligands with different intrinsic activity (CB1 agonist
      methanandamide, CB2 agonist JWH 015, and CB1 antagonist AM 251). METHODS:
      Behavioural interactions of singly-housed mice with non-aggressive group-housed
      partners were video-taped and behavioural elements of agonistic behaviour of
      isolates were recorded in four categories: sociable, timid, aggressive and
      locomotor. RESULTS: Repeated administration of methamphetamine elicited a
      significant sensitization to its antiaggressive effects. Methanandamide pre
      treatment provoked cross-sensitization to this methamphetamine effect, whereas
      pre-treatment with JWH 015 did not. Combined pre-treatment with
      methamphetamine+AM 251 suppressed the sensitization to antiaggressive effects of
      methamphetamine. CONCLUSIONS: Our findings have shown that it is possible to
      provoke sensitization not only to the stimulatory effects as stated widespread in
      the literature but also to inhibitory antiaggressive effects of methamphetamine.
      Furthermore, we confirmed our working hypothesis that it is possible to elicit
      either cross-sensitization to inhibitory effects of methamphetamine conditioned
      by repeated pre-treatment with cannabinoid CB1 receptor agonist methanandamide,
      or suppression of methamphetamine sensitizing influence by co-administration of
      CB1 receptor antagonist.

PMID- 17187026
TI  - Retinal pigment epithelial tear following intravitreal bevacizumab.

PMID- 17187027
TI  - Variation in management during and after retinal surgery for retinopathy of
      prematurity.

PMID- 17187028
TI  - Sildenafil-associated vascular CASUALTIES.

PMID- 17187030
TI  - Effect of posterior capsular opacification on visual function in patients with
      monofocal and multifocal intraocular lenses.
AB  - PURPOSE: To compare the effect of posterior capsular opacification (PCO) on
      visual function in patients with monofocal and multifocal intraocular lenses
      (IOLs). METHODS: Thirty-three consecutive patients with clinically significant
      PCO, 24 with monofocal, and nine with multifocal IOLs, were recruited. Patients
      with concurrent cause of visual loss or pupillary distortion were excluded.
      LogMAR high- and low-contrast (10%) distance visual acuity (VA), logMAR near VA,
      Pelli-Robson contrast sensitivity (CS), colour confusion index (CCI), and the
      presenting symptoms were compared between the two groups. RESULTS: There was no
      significant difference between the proportions of patient with different PCO
      grade in the two groups. At presentation, high- and low-contrast distance VA were
      significantly greater in the multifocal group (0.40 vs 0.20; P=0.04 and 0.34 vs
      0.98; P=0.006), whereas near VA, CS, and CCI were not significantly different
      between the two groups. After capsulotomy, the above visual functions were not
      significantly different between the two groups. Blurred distance and near vision
      were the most common presenting symptoms (95.8 and 100% in the monofocal group
      and 88.9 and 66.7% in the multifocal group). A greater proportion of patients in
      the monofocal group had blurred near vision (100 vs 66.7%) and, whereas the
      symptoms in the majority of patients in the monofocal group were moderate to
      severe, they were mild to moderate in the multifocal group. CONCLUSION: The
      effect of PCO on visual function in the two groups seems to be comparable,
      although patients in the multifocal group appear to present with earlier loss of
      visual function.

PMID- 17187031
TI  - The inadvertent administration of intralenticular triamcinolone.

PMID- 17187032
TI  - Utilization of an ophthalmic casualty--a critical review.

PMID- 17187033
TI  - Medline at thirty-five.

PMID- 17187034
TI  - Conscious sedation guidance.
AB  - SCOPE AND PURPOSE: This guidance is intended to promote good clinical practice
      for the provision in dentistry of conscious sedation that is both safe and
      effective. It is not a recipe book for sedation and therefore does not include
      details of drug dosages. The recommendations are applicable to all patients
      receiving conscious sedation, to facilitate the provision of any type of dental
      treatment whether it is delivered in a dental practice, a community dental
      service clinic or a hospital setting. It also covers the provision of conscious
      sedation for dental treatment provided on a domiciliary basis. Specifically
      excluded from this guidance, however, are patients who require assisted
      ventilation, intensive care sedation, premedication for general anaesthesia,
      postoperative analgesia, sedation in palliative care, night sedation and sedation
      in the home setting other than for the provision of dental treatment on a
      domiciliary basis. METHODS: Existing guidelines, relevant systematic reviews,
      policy documents, legislation or other recommendations were reviewed and
      appraised for their quality of development, evidence base and applicability to
      the remit of the guidance under development. To supplement this information, key
      questions were formulated by the Guidance Development Group and used as the basis
      for designing systematic literature search strategies to identify further
      research evidence that may address these questions, including unpublished work
      where relevant.The following internet sites were searched for guidelines: New
      Zealand Guidelines Group, Canadian Collaboration on Clinical Practice Guidelines
      in Dentistry, National Guidelines Clearinghouse, FDI World Dental Federation,
      National Electronic Library for Health Guideline Finder, and Medline. The
      Cochrane Library was searched for systematic reviews and Medline, Embase and the
      Cochrane Library for studies to address key questions. The searches were
      supplemented by material already known to members of the Guidance Development
      Group. Titles and abstracts of the identified references were screened for
      relevance independently by two researchers who were not members of the Guidance
      Development Group. Disagreement about the inclusion of specific individual
      references for further consideration was resolved by discussion and if necessary
      the opinion of a third researcher was sought. Included references were appraised
      and data was abstracted independently by two researchers using a specifically
      designed data-abstraction form. This information was then checked for
      inconsistencies, which were resolved by discussion, and used to construct
      evidence tables. The evidence tables were presented to the Guidance Development
      Group to inform their decision-making and their recommendations related to the
      key question under consideration. Levels of evidence were assigned by two
      researchers who were not members of the Guidance Development Group. Formulation
      of each recommendation was achieved by consensus reached through discussion,
      drawing on the broad range of interest and experience of sedation related to
      dentistry within the membership of the Guidance Development Group. Consultation
      and peer review were conducted prior to publication. A draft of the guidance was
      the subject of discussion at the Dental Sedation Teachers Group annual symposium
      in April 2004. Subsequently, approximately 100 copies were distributed throughout
      the UK to a range of professional organisations and individuals who have an
      interest in dental sedation, and comments were requested. In addition, all
      dentists in Scotland who recently claimed the National Health Service allowance
      for treatment with sedation were invited to comment. The consultation draft was
      also made available on the group's website (www.scottishdental.org/cep). All
      comments received through this consultation were considered and the guidance was
      amended accordingly prior to peer review. Further amendments were made in
      response to feedback from peer reviewers before publication. REVIEW AND UPDATING:
      The guidance will be reviewed in 2 years' time (2008) and if there have been
      significant changes it will be updated accordingly. RECOMMENDATIONS: The detailed
      guidance make 48 recommendations in a range of areas: REFERRAL: Discuss
      alternative methods of anxiety management with patient and ensure that dental
      care with sedation meets agreed definition of conscious sedation. ASSESSMENT AND
      RECORD KEEPING: As part of a thorough assessment, discuss with patient all
      aspects of their conscious sedation treatment and also provide written
      instructions. Obtain patient's written consent; maintain comprehensive and
      contemporaneous patient records. ENVIRONMENT AND FACILITIES: Ensure that
      environment for sedation is safe and that correct equipment and drugs are
      provided for each sedation technique used. Ensure that equipment and drugs for
      dealing with medical emergencies or complications related to sedation are
      immediately available. TRAINING: Ensure all members of dental team are correctly
      trained in sedation techniques used, including monitoring of patient during
      treatment and management of any sedation-related complications. For oral and
      transmucosal sedation, ensure that sedationist is trained in other titratable
      techniques and skilled in performing venous cannulation. Ensure that teams giving
      conscious sedation provide treatment for patient groups they are experienced in
      managing. CONSCIOUS SEDATION TECHNIQUES: For inhalation sedation, ensure that a
      titrated dose of nitrous oxide is administered using dedicated purpose-designed
      equipment. Oral, transmucosal and intravenous sedation require pulse oximetry and
      blood-pressure monitoring. A titrated dose of midazolam is recommended for
      intravenous sedation. AFTERCARE: Monitor patients throughout the recovery period
      until discharge by sedationist into the care of responsible adult escort who has
      also been given written postoperative instructions. An escort might not be
      required after nitrous oxide inhalation sedation. RESEARCH RECOMMENDATIONS: A
      number of recommendations were made regarding the future conduct and reporting of
      clinical trials. The following areas were highlighted as requiring further high
      quality research: Fasting before conscious sedation. Conscious sedation of
      paediatric dental patients. Dental conscious sedation using combinations of
      drugs. Dental conscious sedation using continuous infusion. The choice of
      sedation method for dental patients. Cognitive and behavioural effects of
      conscious sedation. The interaction of pharmacological and nonpharmacological
      anxiety management techniques. The complete guidance is available for download at
      www.scottishdental.org/cep/guidance/dentalsedation.htm.

PMID- 17187035
TI  - Routine follow-up visits not necessary after third molar removal under sedation.
AB  - DESIGN: This was a randomised controlled trial (RCT) conducted in the US.
      INTERVENTION: People were recruited to the trial who required surgical removal of
      at least two impacted third molars under intravenous sedation on an outpatient
      basis. They were treated by board-certified oral and maxillofacial surgeons.
      Participants were divided randomly into two groups: the first was given a 2-week
      postoperative follow-up appointment, and the other had no follow-up. All patients
      received postoperative instructions and were contacted by telephone on the day
      after surgery. At 2 weeks postoperatively, all patients either returned to the
      clinic or were interviewed by telephone. OUTCOME MEASURE: Patients were asked to
      answer a questionnaire on postoperative day 1 and at 2 weeks after their
      treatment. The questionnaire was originally proposed by Worrall(1) but was
      modified for use in this study. RESULTS: Of the 60 consecutive patients who
      underwent third molar removal, only 48 were included. The mean age was 20 years
      (range, 15-33 years). There were no significant differences in the number of
      patients and gender between the groups receiving clinic or telephone follow-up.
      Seventy-three per cent (35 out of 48) out of all the patients preferred telephone
      follow-up, and 27% (13 out of 48) of patients preferred clinic follow-up. Eighty
      five per cent (29 out of 34) of patients who did not have any complaints on
      postoperative day 1 preferred telephone follow-up (P<0.01). CONCLUSIONS: A
      routine follow-up visit following third molar removal under intravenous sedation
      is not necessary in patients aged between 15 and 35 years. Pre-operative and
      postoperative instructions should be clear, however. A selective review policy
      may be appropriate if a patient is mentally retarded, is taking psychoactive
      drugs, or has an intra-operative complications or a has made a complaint via
      telephone.

PMID- 17187036
TI  - Chlorhexidine varnish has caries-reducing potential.
AB  - DESIGN: A double-blind, randomised, placebo-controlled clinical trial was
      conducted. INTERVENTION: Children in the test group received 6-monthly
      applications of a 40% chlorhexidine varnish whereas children in the control group
      received a placebo varnish, over the course of 2 years. Clinical examination was
      undertaken at baseline and after 24 months by two calibrated dentists who did not
      know to which groups children were assigned. OUTCOME MEASURE: Decayed, missing,
      or primary filled molar surfaces (dmfs-molar) were monitored. RESULTS: At
      baseline, there was no significant difference between the mean dmfs-molar scores
      of the two groups (2.8 vs 2.6; P>0.05 ). After 2 years, 44 children (13%) were
      lost to follow-up, because some (n=31) had moved to other kindergartens, and some
      (n=13) objected to the taste of the varnish and refused to be examined. After 2
      years, 290 children remained in the study, of whom 155 were in the test group and
      135 were in the placebo group. The mean caries increment of the primary molars
      was 1.0 dmfs-molar in the test-group children and 1.6 dmfs-molar in the placebo
      group. The difference of 0.6 tooth surface equated to a 37.3% reduction in caries
      increment (number-needed-to-treat of 3), and was statistically significant (P
      0.036; 95% confidence interval, 0.04-1.16). No side-effects (such as soft-tissue
      lesions and staining of teeth) were found at the 24-month examination.
      CONCLUSIONS: Six-monthly applications of chlorhexidine varnish were effective in
      reducing the incidence of dental caries in primary molars.

PMID- 17187037
TI  - Partial caries removal in symptomless teeth reduces the risk of pulp exposure.
AB  - DATA SOURCES: The Cochrane Oral Health Group Trials Register, Cochrane Central
      Register of Controlled Trials, Medline, PubMed and Embase databases were
      searched. The reference lists in relevant papers were checked. STUDY SELECTION:
      Studies chosen were randomised controlled trials and controlled clinical trials
      that compared minimal (ultraconservative) caries removal with complete caries
      removal in unrestored permanent and deciduous teeth. DATA EXTRACTION AND
      SYNTHESIS: Outcome measures recorded were exposure of the nerve of the tooth
      (pulp) during caries removal, patient experience of symptoms of pulpal
      inflammation or necrosis, progression of caries under the filling, and time until
      the filling was lost or replaced. Because of the heterogeneity of the included
      studies, the overall estimate of effect was calculated using a random-effects
      model. RESULTS: Four studies met the inclusion criteria, comprising two stepwise
      excavation studies and two ultraconservative caries removal studies. Partial
      caries removal in symptomless, primary or permanent teeth reduces the risk of
      pulp exposure. No detriment to the patient was found in terms of pulpal symptoms
      in this procedure and there was no reported premature loss or deterioration of
      the restoration. CONCLUSIONS: Partial caries removal in symptomless, primary or
      permanent teeth reduces the risk of pulp exposure. We found no detriment to the
      patient in terms of pulpal symptoms in this procedure. Therefore, partial caries
      removal is preferable to complete caries removal in the deep lesions in order to
      reduce the risk of carious exposure. There is insufficient evidence, however, to
      know whether it is necessary to re-enter and excavate further - although studies
      that have not re-entered do not report adverse consequences.

PMID- 17187038
TI  - Hard tissue barrier formation after pulp capping?
AB  - DATA SOURCES: Searches for relevant studies were made using Medline and the
      Cochrane Controlled Trials Register (CENTRAL). Reference lists of identified
      articles were searched. STUDY SELECTION: Studies selected were those carried out
      on human teeth, with or without caries, that were treated using a pulp-capping
      procedure and where the hard tissue and pulp were analysed with the aid of a
      microscope. Reviews of pulp capping were searched for references. DATA EXTRACTION
      AND SYNTHESIS: The authors independently extracted the data and assessed the
      level of evidence of each publication as high, moderate or low. Based on this,
      the evidence grade of the conclusions was rated as strong, moderately strong,
      limited or insufficient. RESULTS: Of 107 studies identified, 21 met the selection
      criteria. No study had a high level of evidence, one study was moderate and 20
      studies provided a low level of evidence. There was heterogeneity between the
      studies and therefore no meta-analysis was performed. The majority of studies on
      pulp capping using calcium hydroxide-based materials reported formation of hard
      tissue bridging: studies on other pulp capping materials such as bonding agents
      presented inferior results. CONCLUSIONS: Although the majority of studies using
      calcium hydroxide-based materials reported hard tissue bridging, the quality of
      the available evidence is low. There is a need for more high-quality studies.

PMID- 17187040
TI  - Editor's note. Mineral trioxide aggregate in primary molar pulpotomies.

PMID- 17187039
TI  - Implant retained or conventional dentures, which give more patients satisfaction?
AB  - DESIGN: This was a randomised controlled trial (RCT) set in a dental hospital.
      INTERVENTION: The implant group (IG) had two implants placed in the
      interforaminal region of the lower jaw followed (after healing) by a denture
      fixed to the implants by a ball attachment mechanism. In the conventional
      dentures group (CG), dentures were constructed using conventional replacement
      denture techniques. Patients in the IG had conventional upper dentures made in
      the same fashion. OUTCOME MEASURE: The performance of the dentures was evaluated
      using an oral health impact profile (OHIP) and a denture satisfaction scale
      before treatment and 3 months post-treatment. RESULTS: Analysis was conducted on
      an intention-to-treat basis. Substantial improvements in oral-health-related
      quality of life and denture satisfaction were reported by both groups. There
      were, however, no significant differences post-treatment between the groups.
      Patients randomised to the IG who declined implants had significantly lower
      pretreatment OHIP scores and there were significantly greater pre-/ post
      treatment change-scores for individuals who had implants compared with the change
      scores of people who declined. CONCLUSIONS: There were no significant post
      treatment differences between the groups, but a treatment effect may be masked by
      the intention-to-treat analysis. The pre-/ post-treatment OHIP change-scores were
      significantly greater for people receiving implants than for those who refused.

PMID- 17187041
TI  - Patient's age and extent of coronal and root destruction predict root canal
      treatment subsequent to after a full-cast crown.
AB  - DESIGN: A case-control study was carried out at the University of North Carolina
      School of Dentistry in the US. PARTICIPANT SELECTION: Dental charts from the
      university's dental clinical were audited for patients who had a single-cast
      crown between 1 January 1998 and 31 December 2002. Cases were defined as
      individuals who underwent root canal treatment at some time after the insertion
      of a single-cast crown up to 1 July 2004. The control group consisted of people
      who did not have root canal treatment after the insertion of a full-cast crown.
      DATA ANALYSIS: A list of 24 clinical factors was compared between groups (Table
      1). Multiple logistic regression analysis was used to determine which
      preoperative nonprocedural factors were predictive of root canal treatment
      subsequent to a full-cast crown. RESULTS: A total of 6612 single-cast crowns
      (cast metal or porcelain fused to metal) were inserted during the 5-year period
      of interest. Of these, 5743 crowns, identified from 3357 patients' records (ie,
      the study subjects), were determined not to have undergone root-canal treatment
      prior to full-cast crown restorative treatment. Ninety-two subjects were
      initially determined to be eligible cases; ninety-two subjects were also
      therefore randomly selected from the remaining 3265 subjects to make up the
      control group. Twenty-six of the cases and 21 members of the control group were
      excluded because of incomplete records. The final case and control groups
      comprised 66 and 71 subjects respectively. Only subjects' age at the time of
      restorative treatment and their post-cementation tooth sensitivity was
      statistically significantly different between the two groups (P<0.05). Multiple
      logistic regression determined the statistically significant (P<0.05 ) predictors
      of case status: these were a patient's age and also the subgroup to which they
      were allocated according to the extent of pre-operative coronal and root
      destruction, on the basis of the restorative core size (more than three restored
      surfaces; Table 2). CONCLUSION: The age of a patient and the extent of coronal
      and root destruction can be used to predict the future need for root canal
      treatment on teeth for which a single-cast crown is planned.

PMID- 17187042
TI  - Orthodontic retention regimes: will we ever have the answer?
AB  - DATA SOURCES: The Cochrane Oral Health Group Trials Register, CENTRAL, Medline
      and Embase were searched to May 2005. Key journals were searched by hand,
      together with bibliographies of all retrieved papers and review articles. No
      language restrictions were applied. Authors of trials were contacted to identify
      unpublished trials. STUDY SELECTION: Inclusion criteria specified randomised and
      quasi-randomised controlled trials which involved children or adults who had
      retainers fitted or adjunctive procedures undertaken, following orthodontic
      treatment with braces to prevent relapse. The outcomes were amount of relapse,
      survival of retainers, adverse effects on oral health and quality of life. DATA
      EXTRACTION AND SYNTHESIS: Screening of eligible studies, assessment of the
      methodological quality of the trials and data extraction were conducted
      independently and in duplicate. For dichotomous outcomes, the estimate of effect
      of an intervention was expressed as risk ratios together with 95% confidence
      intervals. For continuous outcomes, mean differences and 95% confidence intervals
      were used to summarise the data for each group. RESULTS: The search identified 27
      articles, of which five met the inclusion criteria. These trials all compared
      different interventions. There was weak unreliable evidence, based on data from
      one trial, that a statistically significant increase in stability occurs in both
      the mandibular (P<0.001) and maxillary anterior segments (P<0.001) when the
      circumferential supracrestal fiberotomy is used in conjunction with a Hawley
      retainer, compared with a Hawley retainer alone. There was also weak, unreliable
      evidence that teeth settle quicker with a Hawley retainer than with a clear
      overlay retainer after 3 months. The quality of the trial reports was generally
      poor. No data were available from any study on quality of life assessment. Meta
      analysis could not be undertaken as no two studies compared the same retention
      techniques. CONCLUSIONS: There are insufficient research data on which to base
      our clinical practice on retention at present. There is an urgent need for high
      quality randomised controlled trials in this crucial area of orthodontic
      practice.

PMID- 17187043
TI  - What is the most effective adhesive for attaching orthodontic bands?
AB  - DATA SOURCES: The Cochrane Oral Health Group's Trials Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL), Medline and Embase were used and
      a search of the internet also undertaken. There was no restriction with regard to
      publication status or language of publication. STUDY SELECTION: Randomised
      controlled trials (RCT) and controlled clinical trials (CCT), including split
      mouth studies, of adhesives used to attach orthodontic bands to molar teeth were
      selected. DATA EXTRACTION AND SYNTHESIS: All review authors were involved in
      study selection, validity assessment and data extraction without blinding to the
      authors, adhesives used or results obtained. All disagreements were resolved by
      discussion. RESULTS: Five RCT and three CCT were identified as meeting the
      review's inclusion criteria. All the included trials were of split-mouth design.
      Four trials compared chemically cured zinc phosphate and chemically cured glass
      ionomer; three trials compared chemically cured glass ionomer cement with light
      cured compomer; one trial compared chemically cured glass ionomer with a
      chemically cured glass phosphonate. Data analysis was often inappropriate within
      the studies that did meet the inclusion criteria. CONCLUSIONS: There is
      insufficient evidence to determine the most effective adhesive for attaching
      orthodontic bands to molar teeth in patients with full-arch fixed orthodontic
      appliances.

PMID- 17187044
TI  - Early treatment of skeletal open-bite malocclusion.
AB  - DATA SOURCES: Studies were identified by searching the Cochrane Controlled
      Clinical Trials Register and Medline. STUDY SELECTION: Randomised clinical trials
      (RCT), prospective and retrospective studies that had concurrent untreated as
      well as normal controls, and clinical trials that compared at least two treatment
      strategies but did not have any untreated or normal control group were included.
      The following were excluded: case series; descriptive studies; case reports;
      studies concerning treatment in the permanent dentition/ adult patients,
      surgically assisted treatment, treatment combined with extractions, treatment
      with full-fixed appliances; and discussion or debate articles. DATA EXTRACTION
      AND SYNTHESIS: Year of publication, study design, materials, dropouts,
      measurements, treatment time, success rate, decrease of open bite and divergence,
      side effects, costs, and authors' conclusions were recorded. Two independent
      reviewers assessed the articles independently and a quality evaluation and
      qualitative summary were performed. RESULTS: A total of 1049 articles were
      identified of which seven were included in the review. No RCT of early treatment
      of anterior open bite have been performed. Two controlled clinical trials of
      early anterior open bite were identified, and these both indicated the
      effectiveness of treatment in the mixed dentition with headgear or functional
      appliances (or both). Most of the studies had serious problems with lack of power
      because of small sample size, bias and confounding variables; lack of method
      error analysis or blinding in measurements; and deficient or lack of statistical
      methods. CONCLUSIONS: The quality of the studies was insufficient to allow any
      evidence-based conclusions to be drawn. RCT of sufficient sample size are still
      needed to determine which treatment is the most effective for early correction of
      skeletal open bite. Future studies should also include the assessment of long
      term stability as well as an analysis of the cost and side-effects of the
      interventions.

PMID- 17187045
TI  - Several therapies may prevent or reduce the severity of oral mucositis associated
      with cancer treatment.
AB  - DATA SOURCES: The Cochrane Oral Health Group Trials Register, Cochrane Central
      Register of Controlled Trials, Medline and Embase were searched to April 2006.
      Reference lists from relevant articles were scanned and the authors of eligible
      studies were contacted to identify trials and obtain additional information.
      STUDY SELECTION: For inclusion, an article had to satisfy the following criteria:
      document a randomised controlled trial (RCT); participants should be people
      receiving chemotherapy or radiotherapy treatment for cancer; prescribe agents to
      prevent oral mucositis; and have the primary outcome of preventing mucositis.
      DATA EXTRACTION AND SYNTHESIS: Data were extracted independently and in
      duplicate. Authors were contacted for details of randomisation and withdrawals
      and a quality assessment was carried out. For dichotomous outcomes, risk ratios
      (RR) were calculated using a random-effects model. RESULTS: The search identified
      202 articles, of which 71 studies had useable data comprising 5217 patients. Of
      the 29 interventions included in the trials, 10 studies showed some evidence of a
      weak benefit for preventing or reducing the severity of mucositis. Interventions
      where more than one trial in the meta-analysis found a significant difference
      compared with placebo/ no treatment were as follows: amifostine: provided minimal
      benefit in preventing moderate and severe mucositis (RR, 0.84 and 0.60,
      respectively); antibiotic paste or pastille: demonstrated moderate benefit in
      preventing mucositis (RR, 0.87); hydrolytic enzymes: reduced moderate and severe
      mucositis (RR, 0.52 and 0.17, respectively); and ice chips: prevented mucositis
      at all levels (RR, 0.63, 0.43 and 0.27). Other interventions showing some benefit
      in only one study were benzydamine, calcium phosphate, honey, oral care
      protocols, povidone and zinc sulphate. CONCLUSIONS: Several of the interventions
      were found to have some benefit at preventing or reducing the severity of
      mucositis associated with cancer treatment. The strength of the evidence was
      variable and implications for practice include consideration that benefits may be
      specific for certain cancer types and treatment. There is a need for well
      designed RCT with sufficient numbers of participants to perform subgroup analyses
      by type of disease and chemotherapeutic agent.

PMID- 17187046
TI  - Prevention of oral mucositis in cancer patients treated with chemotherapy or
      radiotherapy.
AB  - DATA SOURCES: The Medline, Embase and CINAHL databases were used to source
      studies, along with the reference lists of identified articles. STUDY SELECTION:
      Studies were restricted to randomised controlled trials (RCT), written in
      English, where the outcome of mucositis was recorded using the World Health
      Organization score or the NCI-CTC (National Cancer Institute-Common Toxicity
      Criteria) score, the absence or presence of ulcerations, or the presence or
      absence of grades 3 and 4 mucositis. DATA EXTRACTION AND SYNTHESIS: A total of 45
      studies was included in a meta-analysis. When the included studies showed
      heterogeneity regarding the effect estimates, the results of the meta-analyses
      were based on the random-effects models; otherwise, the results were based on the
      fixed-effects models. RESULTS: The search yielded 109 publications, 45 articles
      being included in the meta-analyses. These evaluated eight different
      interventions: local application of chlorhexidine; iseganan; PTA (polymyxin E,
      tobramycine and amphotericin B); granulocyte macrophage-colony-stimulating
      factor/ granulocyte colony-stimulating factor (GM-CSF/ G-CSF); oral cooling;
      sucralfate and glutamine; and systemic administration of amifostine and GM-CSF/G
      CSF. Four interventions showed a significant preventive effect on the development
      or severity of oral mucositis: PTA [odds ratio (OR), 0.61; 95% confidence
      interval (CI), 0.39-0.96]; GM-CSF (OR, 0.53; 95% CI, 0.33-0.87); oral cooling
      (OR, 0.3; 95% CI, 0.16-0.56); and amifostine (OR, 0.37; 95% CI, 0.15-0.89).
      CONCLUSIONS: From current data, it can be concluded that no single intervention
      is capable of completely preventing oral mucositis. Future studies should
      evaluate a combination of interventions for the prevention of oral mucositis. In
      contrast, novel therapies could be developed that will improve outcomes and be
      used as single agents.

PMID- 17187047
TI  - Robust randomised control trials needed for drug treatments for trigeminal
      neuralgia.
AB  - DATA SOURCES: Searches for appropriate studies were made using the following:
      Cochrane Neuromuscular Disease Group Register, Medline, Embase and LILACS (Latin
      American and Caribbean Literature on the Health Sciences) together the Chinese
      Biomedical Retrieval System, the database of the Chinese Cochrane Centre,
      conference paper databases and checked bibliographies. 10 Chinese journals were
      searched by hand. STUDY SELECTION: Randomised controlled trials (RCT) or quasi
      randomised controlled trials were included. DATA EXTRACTION AND SYNTHESIS: Two
      authors decided which trials fitted the inclusion criteria and graded
      methodological quality independently. RESULTS: Nine trials of different non
      antiepileptic drugs involving 223 participants were included. Each trial
      investigated one non-antiepileptic drug. Two trials tested baclofen. In one, more
      people achieved 50% reduction from baseline than with placebo [relative risk
      (RR), 15.00; 95% confidence interval (CI), 0.97-231.84; P 0.05]. In the other,
      slightly more participants who took baclofen showed a 75% reduction in attacks on
      the tenth day compared with carbamazepine (RR, 2.38; 95% CI, 0.83-6.85; P 0.11).
      One trial showed no significant difference in reduction in average daily
      frequency of attacks with Baclofen compared with Racemic Baclofen. Tizanidine was
      investigated in two trials. In one, the proportion of people with a reduction in
      the mean number of paroxysms per day increased with tizanidine compared with
      placebo (RR, 8.00; 95% CI, 1.21-52.69; P 0.03). In the other, one of five
      participants improved their visual analogue scale score with tizanidine and four
      of six did so having taken carbamazepine (RR, 0.30; 95% CI, 0.05-1.89; P 0.20).
      One study showed that the improvement in mean values of pain scores with
      tocainide was similar to that of carbamazepine. In a further trial, more
      participants improved during the pimozide than the carbamazepine period (RR,
      1.78; 95% CI, 1.39-2.28). In another, a 0.5% instillation of proparacaine
      hydrochloride into the eyes did not produce significantly different results from
      placebo (RR, 1.06; 95% CI, 0.37-2.99; P 0.92). Finally, there was moderate or
      marked improvement in a study in seven of nine participants who took clomipramine
      and three of nine who took amitriptyline during a 12-week treatment (RR, 2.33;
      95% CI, 0.87-6.27). CONCLUSIONS: Trials of non-antiepileptic drugs for treating
      trigeminal neuralgia have all been limited by poor methodological quality or poor
      reporting. There is insufficient evidence from randomised clinical trials to show
      significant benefit from non-antiepileptic drugs for trigeminal neuralgia.

PMID- 17187048
TI  - Study design VI - Ecological studies.
AB  - Previously in this series I have given an overview of the main types of study
      design and the techniques used to minimise biased results. In this article I
      describe more fully ecological studies, their uses, advantages and limitations.

PMID- 17187052
TI  - Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and
      acanthosis.
AB  - Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of
      the epidermis (acanthosis), infiltration of leukocytes into both the dermis and
      epidermis, and dilation and growth of blood vessels. The underlying cause of the
      epidermal acanthosis in psoriasis is still largely unknown. Recently, interleukin
      (IL)-23, a cytokine involved in the development of IL-17-producing T helper cells
      (T(H)17 cells), was found to have a potential function in the pathogenesis of
      psoriasis. Here we show that IL-22 is preferentially produced by T(H)17 cells and
      mediates the acanthosis induced by IL-23. We found that IL-23 or IL-6 can
      directly induce the production of IL-22 from both murine and human naive T cells.
      However, the production of IL-22 and IL-17 from T(H)17 cells is differentially
      regulated. Transforming growth factor-beta, although crucial for IL-17
      production, actually inhibits IL-22 production. Furthermore, IL-22 mediates IL-23
      induced acanthosis and dermal inflammation through the activation of Stat3
      (signal transduction and activators of transcription 3) in vivo. Our results
      suggest that T(H)17 cells, through the production of both IL-22 and IL-17, might
      have essential functions in host defence and in the pathogenesis of autoimmune
      diseases such as psoriasis. IL-22, as an effector cytokine produced by T cells,
      mediates the crosstalk between the immune system and epithelial cells.

PMID- 17187053
TI  - Structure prediction for the down state of a potassium channel voltage sensor.
AB  - Voltage-gated potassium (Kv) channels, essential for regulating potassium uptake
      and cell volume in plants and electrical excitability in animals, switch between
      conducting and non-conducting states as a result of conformational changes in the
      four voltage-sensing domains (VSDs) that surround the channel pore. This process,
      known as gating, is initiated by a cluster of positively charged residues on the
      fourth transmembrane segment (S4) of each VSD, which drives the VSD into a 'down
      state' at negative voltages and an 'up state' at more positive voltages. The
      crystal structure of Kv1.2 probably corresponds to the up state, but the local
      environment of S4 in the down state and its motion in voltage gating remains
      unresolved. Here we employed several conditional lethal/second-site suppressor
      yeast screens to determine the transmembrane packing of the VSD in the down
      state. This screen relies on the ability of KAT1, a eukaryotic Kv channel, to
      conduct potassium when its VSDs are in the down state, thereby rescuing potassium
      transport-deficient yeast. Starting with KAT1 channels bearing conditional lethal
      mutations, we identified second-site suppressor mutations throughout the VSD that
      recover yeast growth. We then constructed a down state model of the channel using
      six pairs of interacting residues as structural constraints and verified this
      model by engineering suppressor mutations on the basis of spatial considerations.
      A comparison of this down state model with the up state Kv1.2 structure suggests
      that the VSDs undergo large rearrangements during gating, whereas the S4 segment
      remains positioned between the central pore and the remainder of the VSD in both
      states.

PMID- 17187054
TI  - The APOBEC-2 crystal structure and functional implications for the deaminase AID.
AB  - APOBEC-2 (APO2) belongs to the family of apolipoprotein B messenger RNA-editing
      enzyme catalytic (APOBEC) polypeptides, which deaminates mRNA and single-stranded
      DNA. Different APOBEC members use the same deamination activity to achieve
      diverse human biological functions. Deamination by an APOBEC protein called
      activation-induced cytidine deaminase (AID) is critical for generating high
      affinity antibodies, and deamination by APOBEC-3 proteins can inhibit
      retrotransposons and the replication of retroviruses such as human
      immunodeficiency virus and hepatitis B virus. Here we report the crystal
      structure of APO2. APO2 forms a rod-shaped tetramer that differs markedly from
      the square-shaped tetramer of the free nucleotide cytidine deaminase, with which
      APOBEC proteins share considerable sequence homology. In APO2, two long alpha
      helices of a monomer structure prevent the formation of a square-shaped tetramer
      and facilitate formation of the rod-shaped tetramer via head-to-head interactions
      of two APO2 dimers. Extensive sequence homology among APOBEC family members
      allows us to test APO2 structure-based predictions using AID. We show that AID
      deamination activity is impaired by mutations predicted to interfere with
      oligomerization and substrate access. The structure suggests how mutations in
      patients with hyper-IgM-2 syndrome inactivate AID, resulting in defective
      antibody maturation.

PMID- 17187056
TI  - Sonic hedgehog function in chondrichthyan fins and the evolution of appendage
      patterning.
AB  - The genetic mechanisms regulating tetrapod limb development are well
      characterized, but how they were assembled during evolution and their function in
      basal vertebrates is poorly understood. Initial studies report that
      chondrichthyans, the most primitive extant vertebrates with paired appendages,
      differ from ray-finned fish and tetrapods in having Sonic hedgehog (Shh)
      independent patterning of the appendage skeleton. Here we demonstrate that
      chondrichthyans share patterns of appendage Shh expression, Shh appendage
      specific regulatory DNA, and Shh function with ray-finned fish and tetrapods.
      These studies demonstrate that some aspects of Shh function are deeply conserved
      in vertebrate phylogeny, but also highlight how the evolution of Shh regulation
      may underlie major morphological changes during appendage evolution.

PMID- 17187055
TI  - The nuclear receptor LXR is a glucose sensor.
AB  - The liver has a central role in glucose homeostasis, as it has the distinctive
      ability to produce and consume glucose. On feeding, glucose influx triggers gene
      expression changes in hepatocytes to suppress endogenous glucose production and
      convert excess glucose into glycogen or fatty acids to be stored in adipose
      tissue. This process is controlled by insulin, although debate exists as to
      whether insulin acts directly or indirectly on the liver. In addition to
      stimulating pancreatic insulin release, glucose also regulates the activity of
      ChREBP, a transcription factor that modulates lipogenesis. Here we describe
      another mechanism whereby glucose determines its own fate: we show that glucose
      binds and stimulates the transcriptional activity of the liver X receptor (LXR),
      a nuclear receptor that coordinates hepatic lipid metabolism. d-Glucose and d
      glucose-6-phosphate are direct agonists of both LXR-alpha and LXR-beta. Glucose
      activates LXR at physiological concentrations expected in the liver and induces
      expression of LXR target genes with efficacy similar to that of oxysterols, the
      known LXR ligands. Cholesterol homeostasis genes that require LXR for expression
      are upregulated in liver and intestine of fasted mice re-fed with a glucose diet,
      indicating that glucose is an endogenous LXR ligand. Our results identify LXR as
      a transcriptional switch that integrates hepatic glucose metabolism and fatty
      acid synthesis.

PMID- 17187057
TI  - The twisted ion-permeation pathway of a resting voltage-sensing domain.
AB  - Proteins containing voltage-sensing domains (VSDs) translate changes in membrane
      potential into changes in ion permeability or enzymatic activity. In channels,
      voltage change triggers a switch in conformation of the VSD, which drives gating
      in a separate pore domain, or, in channels lacking a pore domain, directly gates
      an ion pathway within the VSD. Neither mechanism is well understood. In the
      Shaker potassium channel, mutation of the first arginine residue of the S4 helix
      to a smaller uncharged residue makes the VSD permeable to ions ('omega current')
      in the resting conformation ('S4 down'). Here we perform a structure-guided
      perturbation analysis of the omega conductance to map its VSD permeation pathway.
      We find that there are four omega pores per channel, which is consistent with one
      conduction path per VSD. Permeating ions from the extracellular medium enter the
      VSD at its peripheral junction with the pore domain, and then plunge into the
      core of the VSD in a curved conduction pathway. Our results provide a model of
      the resting conformation of the VSD.

PMID- 17187058
TI  - Absolute protein expression profiling estimates the relative contributions of
      transcriptional and translational regulation.
AB  - We report a method for large-scale absolute protein expression measurements
      (APEX) and apply it to estimate the relative contributions of transcriptional-
      and translational-level gene regulation in the yeast and Escherichia coli
      proteomes. APEX relies upon correcting each protein's mass spectrometry sampling
      depth (observed peptide count) by learned probabilities for identifying the
      peptides. APEX abundances agree with measurements from controls, western
      blotting, flow cytometry and two-dimensional gels, as well as known correlations
      with mRNA abundances and codon bias, providing absolute protein concentrations
      across approximately three to four orders of magnitude. Using APEX, we
      demonstrate that 73% of the variance in yeast protein abundance (47% in E. coli)
      is explained by mRNA abundance, with the number of proteins per mRNA log-normally
      distributed about approximately 5,600 ( approximately 540 in E. coli) protein
      molecules/mRNA. Therefore, levels of both eukaryotic and prokaryotic proteins are
      set per mRNA molecule and independently of overall protein concentration, with
      >70% of yeast gene expression regulation occurring through mRNA-directed
      mechanisms.

PMID- 17187059
TI  - F0 generation mice fully derived from gene-targeted embryonic stem cells allowing
      immediate phenotypic analyses.
AB  - A useful approach for exploring gene function involves generating mutant mice
      from genetically modified embryonic stem (ES) cells. Recent advances in genetic
      engineering of ES cells have shifted the bottleneck in this process to the
      generation of mice. Conventional injections of ES cells into blastocyst hosts
      produce F0 generation chimeras that are only partially derived from ES cells,
      requiring additional breeding to obtain mutant mice that can be phenotyped. The
      tetraploid complementation approach directly yields mice that are almost entirely
      derived from ES cells, but it is inefficient, works only with certain hybrid ES
      cell lines and suffers from nonspecific lethality and abnormalities, complicating
      phenotypic analyses. Here we show that laser-assisted injection of either inbred
      or hybrid ES cells into eight cell-stage embryos efficiently yields F0 generation
      mice that are fully ES cell-derived and healthy, exhibit 100% germline
      transmission and allow immediate phenotypic analysis, greatly accelerating gene
      function assignment.

PMID- 17187060
TI  - Retinoblastoma protein and anaphase-promoting complex physically interact and
      functionally cooperate during cell-cycle exit.
AB  - The retinoblastoma protein (pRB) negatively regulates the progression from G1 to
      S phase of the cell cycle, in part, by repressing E2F-dependent transcription.
      pRB also possesses E2F-independent functions that contribute to cell-cycle
      control--for example, during pRB-mediated cell-cycle arrest pRB associates with
      Skp2, the F-box protein of the Skp1-Cullin-F-box protein (SCF) E3 ubiquitin
      ligase complex, and promotes the stability of the cyclin-dependent kinase
      inhibitor p27(Kip1) through an unknown mechanism. Degradation of p27(Kip1) is
      mediated by ubiquitin-dependent targeting of p27(Kip1) by SCF -Skp2 (ref. 4).
      Here, we report a novel interaction between pRB and the anaphase-promoting
      complex/cyclosome (APC/C) that controls p27(Kip1) stability by targeting Skp2 for
      ubiquitin-mediated degradation. Cdh1, an activator of APC/C, not only interacts
      with pRB but is also required for a pRB-induced cell-cycle arrest. The results
      reveal an unexpected physical convergence between the pRB tumour-suppressor
      protein and E3 ligase complexes, and raise the possibility that pRB may direct
      APC/C to additional targets during pRB-mediated cell-cycle exit.

PMID- 17187061
TI  - Myosin VI targeting to clathrin-coated structures and dimerization is mediated by
      binding to Disabled-2 and PtdIns(4,5)P2.
AB  - Vesicle transport is essential for the movement of proteins, lipids and other
      molecules between membrane compartments within the cell. The role of the class VI
      myosins in vesicular transport is particularly intriguing because they are the
      only class that has been shown to move 'backwards' towards the minus end of actin
      filaments. Myosin VI is found in distinct intracellular locations and implicated
      in processes such as endocytosis, exocytosis, maintenance of Golgi morphology and
      cell movement. We have shown that the carboxy-terminal tail is the key targeting
      region and have identified three binding sites: a WWY motif for Disabled-2 (Dab2)
      binding, a RRL motif for glucose-transporter binding protein (GIPC) and
      optineurin binding and a site that binds specifically and with high affinity (Kd
      = 0.3 microM) to PtdIns(4,5)P2-containing liposomes. This is the first
      demonstration that myosin VI binds lipid membranes. Lipid binding induces a large
      structural change in the myosin VI tail (31% increase in helicity) and when
      associated with lipid vesicles, it can dimerize. In vivo targeting and
      recruitment of myosin VI to clathrin-coated structures (CCSs) at the plasma
      membrane is mediated by Dab2 and PtdIns(4,5)P2 binding.

PMID- 17187062
TI  - Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell
      differentiation.
AB  - The transcription factor Gata-3 is a defining marker of the 'luminal' subtypes of
      breast cancer. To gain insight into the role of Gata-3 in breast epithelial
      development and oncogenesis, we have explored its normal function within the
      mammary gland by conditionally deleting Gata-3 at different stages of
      development. We report that Gata-3 has essential roles in the morphogenesis of
      the mammary gland in both the embryo and adult. Through the discovery of a novel
      marker (beta3-integrin) of luminal progenitor cells and their purification, we
      demonstrate that Gata-3 deficiency leads to an expansion of luminal progenitors
      and a concomitant block in differentiation. Remarkably, introduction of Gata-3
      into a stem cell-enriched population induced maturation along the alveolar
      luminal lineage. These studies provide evidence for the existence of an
      epithelial hierarchy within the mammary gland and establish Gata-3 as a critical
      regulator of luminal differentiation.

PMID- 17187063
TI  - Abnormal bundling and accumulation of F-actin mediates tau-induced neuronal
      degeneration in vivo.
AB  - Hyperphosphorylated forms of the microtubule-associated protein (MAP) tau
      accumulate in Alzheimer's disease and related tauopathies and are thought to have
      an important role in neurodegeneration. However, the mechanisms through which
      phosphorylated tau induces neurodegeneration have remained elusive. Here, we show
      that tau-induced neurodegeneration is associated with accumulation of filamentous
      actin (F-actin) and the formation of actin-rich rods in Drosophila and mouse
      models of tauopathy. Importantly, modulating F-actin levels genetically leads to
      dramatic modification of tau-induced neurodegeneration. The ability of tau to
      interact with F-actin in vivo and in vitro provides a molecular mechanism for the
      observed phenotypes. Finally, we show that the Alzheimer's disease-linked human
      beta-amyloid protein (Abeta) synergistically enhances the ability of wild-type
      tau to promote alterations in the actin cytoskeleton and neurodegeneration. These
      findings raise the possibility that a direct interaction between tau and actin
      may be a critical mediator of tau-induced neurotoxicity in Alzheimer's disease
      and related disorders.

PMID- 17187064
TI  - Structural basis for modulation of Kv4 K+ channels by auxiliary KChIP subunits.
AB  - KChIPs coassemble with pore-forming Kv4 alpha subunits to form a native complex
      in the brain and heart and regulate the expression and gating properties of Kv4
      K(+) channels, but the mechanisms underlying these processes are unknown. Here we
      report a co-crystal structure of the complex of human Kv4.3 N-terminus and KChIP1
      at a 3.2-A resolution. The structure reveals a unique clamping action of the
      complex, in which a single KChIP1 molecule, as a monomer, laterally clamps two
      neighboring Kv4.3 N-termini in a 4:4 manner, forming an octamer. The proximal N
      terminal peptide of Kv4.3 is sequestered by its binding to an elongated groove on
      the surface of KChIP1, which is indispensable for the modulation of Kv4.3 by
      KChIP1, and the same KChIP1 molecule binds to an adjacent T1 domain to stabilize
      the tetrameric Kv4.3 channels. Taken together with biochemical and functional
      data, our findings provide a structural basis for the modulation of Kv4 by
      KChIPs.

PMID- 17187065
TI  - Separate neural substrates for skill learning and performance in the ventral and
      dorsal striatum.
AB  - It is widely accepted that the striatum of the basal ganglia is a primary
      substrate for the learning and performance of skills. We provide evidence that
      two regions of the rat striatum, ventral and dorsal, play distinct roles in
      instrumental conditioning (skill learning), with the ventral striatum being
      critical for learning and the dorsal striatum being important for performance
      but, notably, not for learning. This implies an actor (dorsal) versus director
      (ventral) division of labor, which is a new variant of the widely discussed actor
      critic architecture. Our results also imply that the successful performance of a
      skill can ultimately result in its establishment as a habit outside the basal
      ganglia.

PMID- 17187066
TI  - Negative normal stress in semiflexible biopolymer gels.
AB  - When subject to stress or external loads, most materials resist deformation. Any
      stable material, for instance, resists compression-even liquids. Solids also
      resist simple shear deformations that conserve volume. Under shear, however, most
      materials also have a tendency to expand in the direction perpendicular to the
      applied shear stress, a response that is known as positive normal stress. For
      example, wet sand tends to dilate when sheared, and therefore dries around our
      feet when we walk on the beach. In the case of simple solids, elastic rods or
      wires tend to elongate when subject to torsion. Here, we show that networks of
      semiflexible biopolymers such as those that make up both the cytoskeleton of
      cells and the extracellular matrix exhibit the opposite tendency: when sheared
      between two plates, they tend to pull the plates together. We show that these
      negative normal stresses can be as large as the shear stress and that this
      property is directly related to the nonlinear strain-stiffening behaviour of
      biopolymer gels.

PMID- 17187067
TI  - The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral
      lipid storage disease with myopathy.
AB  - Neutral lipid storage disease comprises a heterogeneous group of autosomal
      recessive disorders characterized by systemic accumulation of triglycerides in
      cytoplasmic droplets. Here we report a neutral lipid storage disease subgroup
      characterized by mild myopathy, absence of ichthyosis and mutations in both
      alleles of adipose triglyceride lipase (PNPLA2, also known as ATGL). Three of
      these mutations are predicted to lead to a truncated ATGL protein with an intact
      patatin domain containing the active site, but with defects in the hydrophobic
      domain. The block in triglyceride degradation was mimicked by short interfering
      RNA directed against ATGL. NLSDM is distinct from Chanarin-Dorfman syndrome,
      which is characterized by neutral lipid storage disease with ichthyosis, mild
      myopathy and hepatomegaly due to mutations in ABHD5 (also known as CGI-58).

PMID- 17187068
TI  - HAX1 deficiency causes autosomal recessive severe congenital neutropenia
      (Kostmann disease).
AB  - Autosomal recessive severe congenital neutropenia (SCN) constitutes a primary
      immunodeficiency syndrome associated with increased apoptosis in myeloid cells,
      yet the underlying genetic defect remains unknown. Using a positional cloning
      approach and candidate gene evaluation, we identified a recurrent homozygous
      germline mutation in HAX1 in three pedigrees. After further molecular screening
      of individuals with SCN, we identified 19 additional affected individuals with
      homozygous HAX1 mutations, including three belonging to the original pedigree
      described by Kostmann. HAX1 encodes the mitochondrial protein HAX1, which has
      been assigned functions in signal transduction and cytoskeletal control. Here, we
      show that HAX1 is critical for maintaining the inner mitochondrial membrane
      potential and protecting against apoptosis in myeloid cells. Our findings suggest
      that HAX1 is a major regulator of myeloid homeostasis and underline the
      significance of genetic control of apoptosis in neutrophil development.

PMID- 17187070
TI  - Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T
      cell receptor signals toward NFAT but not NF-kappaB transcription factors.
AB  - Tyrosine kinases couple the T cell receptor (TCR) to discrete signaling cascades,
      each of which is capable of inducing a distinct functional outcome. Precisely how
      TCR signals are channeled toward specific targets remains unclear. TCR
      stimulation triggers 'alternative' activation of the mitogen-activated protein
      kinase p38, whereby the Lck and Zap70 tyrosine kinases directly activate p38.
      Here we report that alternatively activated p38 associated with the Dlgh1 MAGUK
      scaffold protein. 'Knockdown' of Dlgh1 expression blocked TCR-induced activation
      of p38 and the transcription factor NFAT but not of the mitogen-activated protein
      kinase Jnk or transcription factor NF-kappaB. A Dlgh1 mutant incapable of binding
      p38 failed to activate NFAT. Along with reports that the CARMA1 MAGUK scaffold
      protein coordinates activation of Jnk and NF-kappaB but not of p38 or NFAT, our
      findings identify MAGUK scaffold proteins as 'orchestrators' of TCR signal
      specificity.

PMID- 17187069
TI  - The adaptor protein CARD9 is required for innate immune responses to
      intracellular pathogens.
AB  - The caspase-recruitment domain-containing adaptor protein CARD9 regulates the
      innate signaling responses to fungal infection. Here we show that CARD9 is
      required for innate immune responses against intracellular pathogens. We
      generated Card9(-/-) mice and found that CARD9-deficient macrophages had defects
      in activation of the kinases p38 and Jnk but not of transcription factor NF
      kappaB after bacterial and viral infection. CARD9-deficient mice failed to clear
      infection and showed altered cytokine production after challenge with Listeria
      monocytogenes. In wild-type cells, we found CARD9 inducibly associated with both
      the intracellular 'biosensor' Nod2 and the serine-threonine kinase RICK. Our data
      demonstrate that CARD9 has a critical function in Nod2-mediated activation of p38
      and Jnk in innate immune responses to intracellular pathogens.

PMID- 17187071
TI  - Antigen-receptor genes of the agnathan lamprey are assembled by a process
      involving copy choice.
AB  - Jawless vertebrates have acquired immunity but do not have immunoglobulin-type
      antigen receptors. Variable lymphocyte receptors (VLRs) have been identified in
      lamprey that consist of multiple leucine-rich repeat (LRR) modules. An active VLR
      gene is generated by the assembly of a series of variable gene segments,
      including many that encode LRRs. Stepwise assembly of the gene segments seems to
      occur by replacement of the intervening DNA between the 5' and 3' constant-region
      genes. Here we report that lamprey (Lethenteron japonicum) assemble their VLR
      genes by a process involving 'copy choice'. Regions of short homology seemed to
      prime copying of donor LRR-encoding sequences into the recipient gene. Those LRR
      encoding germline sequences were abundant and shared extensive sequence
      homologies. Such genomic organization permits initiation of copying anywhere in
      an LRR-encoding module for the generation of various hybrid LRRs. Thus, a vast
      repertoire of recombinant VLR genes could be generated not only by copying of
      various LRR segments in diverse combinations but also by the use of multiple
      sites in an LRR gene segment for priming.

PMID- 17187072
TI  - Calreticulin exposure dictates the immunogenicity of cancer cell death.
AB  - Anthracyclin-treated tumor cells are particularly effective in eliciting an
      anticancer immune response, whereas other DNA-damaging agents such as etoposide
      and mitomycin C do not induce immunogenic cell death. Here we show that
      anthracyclins induce the rapid, preapoptotic translocation of calreticulin (CRT)
      to the cell surface. Blockade or knockdown of CRT suppressed the phagocytosis of
      anthracyclin-treated tumor cells by dendritic cells and abolished their
      immunogenicity in mice. The anthracyclin-induced CRT translocation was mimicked
      by inhibition of the protein phosphatase 1/GADD34 complex. Administration of
      recombinant CRT or inhibitors of protein phosphatase 1/GADD34 restored the
      immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced
      their antitumor effects in vivo. These data identify CRT as a key feature
      determining anticancer immune responses and delineate a possible strategy for
      immunogenic chemotherapy.

PMID- 17187073
TI  - Artificially engineered magnetic nanoparticles for ultra-sensitive molecular
      imaging.
AB  - Successful development of ultra-sensitive molecular imaging nanoprobes for the
      detection of targeted biological objects is a challenging task. Although magnetic
      nanoprobes have the potential to perform such a role, the results from probes
      that are currently available have been far from optimal. Here we used artificial
      engineering approaches to develop innovative magnetic nanoprobes, through a
      process that involved the systematic evaluation of the magnetic spin, size and
      type of spinel metal ferrites. These magnetism-engineered iron oxide (MEIO)
      nanoprobes, when conjugated with antibodies, showed enhanced magnetic resonance
      imaging (MRI) sensitivity for the detection of cancer markers compared with
      probes currently available. Also, we successfully visualized small tumors
      implanted in a mouse. Such high-performance, nanotechnology-based molecular
      probes could enhance the ability to visualize other biological events critical to
      diagnostics and therapeutics.

PMID- 17187074
TI  - Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global
      HIV-1 variants.
AB  - HIV-1/AIDS vaccines must address the extreme diversity of HIV-1. We have designed
      new polyvalent vaccine antigens comprised of sets of 'mosaic' proteins, assembled
      from fragments of natural sequences via a computational optimization method.
      Mosaic proteins resemble natural proteins, and a mosaic set maximizes the
      coverage of potential T-cell epitopes (peptides of nine amino acids) for a viral
      population. We found that coverage of viral diversity using mosaics was greatly
      increased compared to coverage by natural-sequence vaccine candidates, for both
      variable and conserved proteins; for conserved HIV-1 proteins, global coverage
      may be feasible. For example, four mosaic proteins perfectly matched 74% of 9
      amino-acid potential epitopes in global Gag sequences; 87% of potential epitopes
      matched at least 8 of 9 positions. In contrast, a single natural Gag protein
      covered only 37% (9 of 9) and 67% (8 of 9). Mosaics provide diversity coverage
      comparable to that afforded by thousands of separate peptides, but, because the
      fragments of natural proteins are compressed into a small number of native-like
      proteins, they are tractable for vaccines.

PMID- 17187075
TI  - An arginine ladder in OprP mediates phosphate-specific transfer across the outer
      membrane.
AB  - The outer membrane protein OprP mediates the transport of essential phosphate
      anions into the pathogenic bacterium Pseudomonas aeruginosa. Here we report the
      crystallographic structure of trimeric OprP at 1.9-A resolution, revealing an
      unprecedented 9-residue arginine 'ladder' that spans from the extracellular
      surface down through a constriction zone where phosphate is coordinated. Lysine
      residues coat the inner periplasmic surface, creating an 'electropositive sink'
      that pulls the phosphates through the eyelet and into the cell.

PMID- 17187076
TI  - Identification and structural basis of binding to host lung glycogen by
      streptococcal virulence factors.
AB  - The ability of pathogenic bacteria to recognize host glycans is often essential
      to their virulence. Here we report structure-function studies of previously
      uncharacterized glycogen-binding modules in the surface-anchored pullulanases
      from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA).
      Multivalent binding to glycogen leads to a strong interaction with alveolar type
      II cells in mouse lung tissue. X-ray crystal structures of the binding modules
      reveal a novel fusion of tandem modules into single, bivalent functional domains.
      In addition to indicating a structural basis for multivalent attachment, the
      structure of the SpuA modules in complex with carbohydrate provides insight into
      the molecular basis for glycogen specificity. This report provides the first
      evidence that intracellular lung glycogen may be a novel target of pathogenic
      streptococci and thus provides a rationale for the identification of the
      streptococcal alpha-glucan-metabolizing machinery as virulence factors.

PMID- 17187077
TI  - SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in
      stem cells.
AB  - The Tr2 orphan nuclear receptor can be SUMOylated, resulting in the replacement
      of coregulators recruited to the regulatory region of its endogenous target gene,
      Oct4. UnSUMOylated Tr2 activates Oct4, enhancing embryonal carcinoma-cell
      proliferation, and is localized to the promyelocytic leukemia (Pml) nuclear
      bodies. When its abundance is elevated, Tr2 is SUMOylated at Lys238 and seems to
      be released from the nuclear bodies to act as a repressor. SUMOylation of Tr2
      induces an exchange of its coregulators: corepressor Rip140 replaces coactivator
      Pcaf, which switches Tr2 from an activator to a repressor. This involves dynamic
      partitioning of Tr2 into Pml-containing and Pml-free pools. These results support
      a model where SUMOylation-dependent partitioning and differential coregulator
      recruitment contribute to the maintenance of a homeostatic supply of activating,
      as opposed to repressive, Tr2, thus fine-tuning Oct4 expression and regulating
      stem-cell proliferation.

PMID- 17187078
TI  - An Escherichia coli expression-based method for heme substitution.
AB  - Heme reconstitution with porphyrin analogs is a powerful approach toward
      understanding the molecular function of heme proteins; present methods, however,
      have not proven to be generally useful. Here we describe the development and
      application of an expression-based method for introducing modified porphyrins.
      The approach allows efficient incorporation of heme analogs using a widely
      available bacterial strain and offers an attractive alternative to present
      reconstitution methods that subject proteins to harsh, denaturing conditions.

PMID- 17187079
TI  - Structure of acid beta-glucosidase with pharmacological chaperone provides
      insight into Gaucher disease.
AB  - Gaucher disease results from mutations in the lysosomal enzyme acid beta
      glucosidase (GCase). Although enzyme replacement therapy has improved the health
      of some affected individuals, such as those with the prevalent N370S mutation,
      oral treatment with pharmacological chaperones may be therapeutic in a wider
      range of tissue compartments by restoring sufficient activity of endogenous
      mutant GCase. Here we demonstrate that isofagomine (IFG, 1) binds to the GCase
      active site, and both increases GCase activity in cell lysates and restores
      lysosomal trafficking in cells containing N370S mutant GCase. We also compare the
      crystal structures of IFG-bound GCase at low pH with those of glycerol-bound
      GCase at low pH and apo-GCase at neutral pH. Our data indicate that IFG induces
      active GCase, which is secured by interactions with Asn370. The design of small
      molecules that stabilize substrate-bound conformations of mutant proteins may be
      a general therapeutic strategy for diseases caused by protein misfolding and
      mistrafficking.

PMID- 17187080
TI  - Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does
      not induce Paget disease.
AB  - Paget disease is the most exaggerated example of abnormal bone remodeling, with
      the primary cellular abnormality in the osteoclast. Mutations in the p62
      (sequestosome 1) gene occur in one-third of patients with familial Paget disease
      and in a minority of patients with sporadic Paget disease, with the P392L amino
      acid substitution being the most commonly observed mutation. However, it is
      unknown how p62(P392L) mutation contributes to the development of this disease.
      To determine the effects of p62(P392L) expression on osteoclasts in vitro and in
      vivo, we introduced either the p62(P392L) or WT p62 gene into normal osteoclast
      precursors and targeted p62(P392L) expression to the osteoclast lineage in
      transgenic mice. p62(P392L)-transduced osteoclast precursors were hyperresponsive
      to receptor activator of NF-kappaB ligand (RANKL) and TNF-alpha and showed
      increased NF-kappaB signaling but did not demonstrate increased 1,25-(OH)(2)D(3)
      responsivity, TAF(II)-17 expression, or nuclear number per osteoclast. Mice
      expressing p62(P392L) developed increased osteoclast numbers and progressive bone
      loss, but osteoblast numbers were not coordinately increased, as is seen in Paget
      disease. These results indicate that p62(P392L) expression on osteoclasts is not
      sufficient to induce the full pagetic phenotype but suggest that p62 mutations
      cause a predisposition to the development of Paget disease by increasing the
      sensitivity of osteoclast precursors to osteoclastogenic cytokines.

PMID- 17187083
TI  - Nonhomogeneous immunostaining of hyaline membranes in different manifestations of
      diffuse alveolar damage.
AB  - PURPOSE: To determine the nature of hyaline membranes in different manifestations
      of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory
      distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND
      METHODS: Pulmonary specimens were obtained from 17 patients with acute
      respiratory distress syndrome and 9 patients with acute interstitial pneumonia.
      They were separated into 3 different groups: (a) pulmonary diffuse alveolar
      damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary
      diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock
      cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of
      idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark
      of the diffuse alveolar damage histological pattern, were examined using various
      kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP
      A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (alpha
      SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor
      VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of
      hyaline membranes (12.65% +/- 3.24%), while extrapulmonary diffuse alveolar
      damage (9.52% +/- 3.64%) and idiopathic diffuse alveolar damage (7.34% +/- 2.11%)
      showed intermediate and lower amounts, respectively, with the difference being
      statistically significant between pulmonary and idiopathic diffuse alveolar
      damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A
      immunostaining among pulmonary (15.36% +/- 3.12%), extrapulmonary (16.12% +/-
      4.58%), and idiopathic (13.74 +/- 4.20%) diffuse alveolar damage groups.
      Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented
      larger amounts of immunostained hyaline membranes (14.12% +/- 6.25%) than
      extrapulmonary diffuse alveolar damage (3.93% +/- 2.86%), with this difference
      being statistically significant (P < 0.001). Equally significant was the
      difference for progressive decrease of cytokeratin AE1/AE3 immunostaining in
      hyaline membranes present in the extrapulmonary diffuse alveolar damage (5.42% +/
      2.80%) and idiopathic diffuse alveolar damage (0.47% +/- 0.81%) groups (P <
      0.001). None of the groups stained for cytokeratin CK-7, CK-8, vimentin, or a
      anti-smooth muscle actin. CONCLUSIONS: This study showed that only the
      epithelial/endothelial components (SP-A, factor VIII, and AE1/AE3) of the
      alveolar/capillary barrier are present in hyaline membranes formation in the 3
      groups of patients with diffuse alveolar damage. The significant difference in
      the expression of factor VIII-related antigen and cytokeratin AE1/AE3 in the
      expDA versus iDAD groups as well as the significant difference in the amount of
      hyaline membranes present in the pDAD versus iDAD groups are suggestive of a
      local and specific lesion with different pathways (direct, indirect, or
      idiopathic), depending on the type of diffuse alveolar damage.

PMID- 17187084
TI  - Study of the prevalence and risk factors for low back pain in truck drivers in
      the state of Sao Paulo, Brazil.
AB  - OBJECTIVE: To investigate the prevalence of low back pain in truck drivers and
      check for possible risk factors related to the presence of low back pain.
      METHODS: A questionnaire was developed including personal factors such as age,
      practice of physical and sports activities, general health habits, occupation
      related issues, and factors associated with low back pain. The body mass index
      (ratio of body weight to the square of height, kg/m2) was calculated. Of 489 male
      truck drivers assessed, 410 were enrolled into the study. The statistical
      analysis was divided into 2 stages: descriptive analysis of data, and binary
      logistical regression, where the response (dependent) variable (presence of low
      back pain) was associated with each independent variable to check for correlation
      with low back pain. RESULTS: Of the 410 truck drivers evaluated, 242 (59%)
      presented with low back pain, while 168 (41%) did not have low back pain. The
      only factor correlated with the presence of low back pain was the number of
      working hours; the other factors had no correlation with low back pain.
      CONCLUSION: The prevalence of low back pain in truck drivers was 59%. The number
      of working hours was the only variable associated with occurrence of low back
      pain, with an average of about 1 hour longer work time for drivers with low back
      pain compared to those without it and with an odds ratio of 1.07 (P = 0.026).

PMID- 17187085
TI  - Dynamic contour tonometry and goldman applanation tonometry in eyes with
      keratoconus.
AB  - PURPOSE: The dynamic contour tonometer is a nonapplanation contact tonometer
      designed to be largely independent of the structural properties of the cornea.
      Theoretically, it may measure intraocular pressure most accurately in abnormally
      thinner corneas. This study compares intraocular pressure measurements by dynamic
      contour tonometry with Goldman applanation tonometry in eyes with normal corneas
      and eyes with advanced keratoconus. METHODS: A comparative case series. Subjects
      underwent intraocular pressure measurements by dynamic contour tonometry, Goldman
      applanation tonometry, ultrasonic pachymetry, and slit scanning topography.
      EXCLUSION CRITERIA: any ocular pathology other than keratoconus, previous corneal
      or refractive surgery, stromal scarring due to acute hydrops, or any other
      corneal opacities. RESULTS: Ten patients with keratoconus were included in Group
      A, and 12 normal patients composed Group B according to the pre-established
      criteria. The mean Goldman tonometry measurement in group A was 10.3 +/- 1.8 mm
      Hg and group B was 14.3 +/- 0.75 mm Hg. (P = 0.024). In group A, the mean
      measurement with the dynamic contour tonometer was 14.6 +/- 2.09 mm Hg, and in
      group B, it was 17.4 +/- 3.1 mm Hg (P = 0.026). The difference between both
      methods of measurement in group A was statistically significant (P < 0.0002).
      CONCLUSION: Intraocular pressure readings with dynamic contour tonometry in the
      keratoconus group were significantly higher than Goldman measurements and lower
      when compared to the control group. As there are no published manometric studies
      in eyes with keratoconus, these lower intra-ocular readings with the dynamic
      contour tonometry could be related to the discrepancy between the radius of
      corneal curvature and its tip, the significant thinning of the cornea, or other
      corneal biomechanical abnormalities related to advanced keratoconus.

PMID- 17187081
TI  - Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and
      energy expenditure.
AB  - The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) control glucose homeostasis through well-defined
      actions on the islet beta cell via stimulation of insulin secretion and
      preservation and expansion of beta cell mass. We examined the importance of
      endogenous incretin receptors for control of glucose homeostasis through analysis
      of Glp1r(-/-), Gipr(-/-), and double incretin receptor knockout (DIRKO) mice fed
      a high-fat (HF) diet. DIRKO mice failed to upregulate levels of plasma insulin,
      pancreatic insulin mRNA transcripts, and insulin content following several months
      of HF feeding. Both single incretin receptor knockout and DIRKO mice exhibited
      resistance to diet-induced obesity, preservation of insulin sensitivity, and
      increased energy expenditure associated with increased locomotor activity.
      Moreover, plasma levels of plasminogen activator inhibitor-1 and resistin failed
      to increase significantly in DIRKO mice after HF feeding, and the GIP receptor
      agonist [D-Ala(2)]GIP, but not the GLP-1 receptor agonist exendin-4, increased
      the levels of plasma resistin in studies of both acute and chronic
      administration. These findings extend our understanding of how endogenous
      incretin circuits regulate glucose homeostasis independent of the beta cell via
      control of adipokine secretion and energy expenditure.

PMID- 17187086
TI  - A pharmacoepidemiologic study of drug interactions in a Brazilian teaching
      hospital.
AB  - PURPOSE: Although drug-drug interactions constitute only a small proportion of
      adverse drug reactions, they are often predictable and therefore avoidable or
      manageable. There are few studies on drug-drug interactions from Brazil. This
      study aimed to assess the frequency of drug-drug interactions in prescriptions
      and their potential clinical significance in patients of a Brazilian teaching
      hospital. METHODS: From January to April 2004, a sample of 1785 drug
      prescriptions was drawn from a total of 11,250. Drug-drug interactions were
      identified by using Micromedex DrugReax System. Patients'records with major drug
      drug interactions were reviewed by a pharmacist and a medical doctor looking for
      signs, symptoms, and lab tests that could indicate adverse drug reactions due to
      such interactions. RESULTS: From the 1785 prescriptions examined, 1089 (61%) were
      from the male adult ward. Patients' average age was 52.7 years (SD = 18.9; range,
      12-98). The median number of drugs in each prescription was 7 (range, 2-26). At
      least 1 drug-drug interactions was present in 887 (49.7%) prescriptions.
      Regarding the severity of the clinical result, the interactions were classified
      as minor (20; 2.3%), moderate (184; 20.7%), major (30; 3.4%), and undetermined
      because of an incidence of more than 1 interaction in a single patient (653;
      73.6%). From the 30 patients with major interactions, 17 (56.7%) presented
      adverse drug reactions induced by exposure to a major drug-drug interaction.
      CONCLUSIONS: Patients did suffer adverse drug reactions from major drug-drug
      interactions. Many physicians may be unaware of drug-drug interactions.
      Education, computerized prescribing systems and drug information, collaborative
      drug selection, and pharmaceutical care are strongly encouraged for physicians
      and pharmacists.

PMID- 17187087
TI  - Evaluation of physiotherapy in the treatment of Legg-Calve-Perthes disease.
AB  - INTRODUCTION: Physiotherapy using muscle strengthening and stretching exercises
      is claimed to have beneficial effects in the treatment of Legg-Calve-Perthes
      disease; however, no scientific evidence is available concerning effectiveness of
      treatment. PURPOSE: The purpose of the present study was to clinically evaluate
      possible effects of the proposed physiotherapeutic effects compared to
      observational follow-up in patients with Legg-Calve-Perthes disease. METHOD: A
      prospective follow-up study was conducted in 17 patients with unilateral Legg
      Calve-Perthes disease, divided into 2 groups: Group A (observational follow-up)
      and Group B (physiotherapeutic follow-up). In order to evaluate the outcome of
      the adopted treatments, the following parameters were assessed: articular range
      of motion, level of muscular strength, level of articular dysfunction, and
      radiographic status, both before and after the treatment. RESULTS: Group B
      exhibited significant improvement in articular range of motion concerning hip
      flexion, extension, abduction, adduction, medial rotation, and lateral rotation,
      while in Group A an equally significant worsening occurred concerning abduction,
      adduction, and medial rotation. Muscular strength also improved in Group B,
      mainly in the set of hip flexor muscles, while Group A showed no changes.
      Articular dysfunction after therapy compared to pretherapy was significantly
      reduced in Group B and increased in Group A. Patients undergoing physiotherapy
      exercises showed no changes in their radiographic features. CONCLUSION:
      Physiotherapy produced significant improvement in articular range of motion,
      muscular strength, and articular dysfunction in patients with Legg-Calve-Perthes
      disease, but these improvements were not evident on radiographs.

PMID- 17187088
TI  - Bilateral nephrectomy of huge polycystic kidneys associated with a rectus
      abdominis diastasis and umbilical hernia.
AB  - BACKGROUND: Patients with end-stage renal failure due to huge autosomal dominant
      polycystic kidney disease usually have an umbilical hernia and rectus abdominis
      diastasis, which are very troublesome. Pretransplant bilateral nephrectomy
      techniques does not manage the umbilical hernia and rectus abdominis diastasis.
      We report our experience in performing bilateral nephrectomy and repairing the
      rectus abdominis diastasis and umbilical hernia through the one, small incision.
      METHODS: Four patients aged 37 to 43 years with huge polycystic kidneys, an
      umbilical hernia, and a rectus abdominis diastasis underwent bilateral
      pretransplant nephrectomy through a midline supraumbilical incision including the
      umbilical hernia defect. The kidneys were removed through this incision. The
      incision was closed with the transposition of rectus abdominis muscle, pants-over
      vest-style, to correct the diastasis and the umbilical hernia. RESULTS: The
      average operative time was 160 minutes (range, 130-180); the average larger
      kidney size was 33 cm (range, 32-34 cm); no major complications occurred; one
      patient who had preoperative low hemoglobin required blood transfusion. Patients
      were discharged from the hospital on postoperative day 7 with an esthetically
      pleasing belly, no rectus abdominis diastasis, and no umbilical hernia. One to
      two months after bilateral nephrectomy, the patients received a live donor kidney
      with an uneventful outcome. CONCLUSION: A midline supraumbilical incision is an
      excellent approach for bilateral nephrectomy of huge polycystic kidneys. In
      addition, an umbilical hernia and rectus abdominis diastasis may be successfully
      repaired through same incision with good cosmetic results.

PMID- 17187089
TI  - Performance of patients with intermittent claudication undergoing physical
      training, with or without an aggravation of arterial disease: retrospective
      cohort study.
AB  - PURPOSE: This was a retrospective cohort study aiming to investigate the clinical
      outcome of patients with intermittent claudication undergoing physical training
      in whom there was an aggravation of the arterial disease. METHOD: Three hundred
      and sixty-four patients with claudication who presented with femoropopliteal or
      tibioperoneal obstructions in at least 1 of the lower limbs and who did not have
      aortic or bilateral iliac obstructions were included. Forty patients developed
      new stenoses in previously spared arterial segments (confirmed by duplex
      scanning), which were proximal to preexisting lesions, and formed the progression
      group, in contrast to the stable group of patients (n = 324) who did not exhibit
      this worsening of the disease. Follow-up was 276 and 277 days for stable and
      progression groups, respectively. All patients underwent an unsupervised program
      of submaximal walking 4 days a week. Changes in maximal walking distance at a
      progressive treadmill test were appraised during follow-up, with special interest
      directed to the periods between admission, diagnosis of arterial worsening, and
      the end of follow-up. RESULTS: Performance was not significantly different
      between groups during the entire follow-up period. Furthermore, patients with
      claudication who evolved with progression of their arteriopathy did not present a
      reduction of their maximal walking distance in response to the development of new
      arterial lesions at any time during their follow-up. CONCLUSION: Worsening of the
      peripheral arterial disease in patients with claudication undergoing physical
      training, manifested as de novo arterial occlusion in proximal and previously
      spared segments, does not imply in an impairment of their claudication distance.

PMID- 17187090
TI  - Evolution of Brazilian elderly with hip fracture secondary to a fall.
AB  - OBJECTIVE: To contribute to fall prevention by studying the epidemiological
      profile, mortality, and functional evolution of elderly persons with hip
      fracture, in Brazil, in the year following a fracture. METHOD: Fifty-six elderly
      patients aged 60 years and over with hip fracture secondary to a fall and
      admitted in 2000 were included. In addition to the medical record data, patients
      or their guardians filled a form providing information regarding personal data,
      history of fall and fracture, physical evaluation, and ability to perform basic
      and instrumental activities of daily living prior to and 1 year after their
      fracture, using Katz's Index and Lawton's Index, respectively. RESULTS: Fractures
      were more common among Caucasian widowed women, and most falls occurred at home.
      General mortality within 1 year after the occurrence of fracture was 30.35% and
      was associated with sex and age. There was an increase in the inability to walk
      and in the use of a supporting device. A significant reduction in the functional
      ability to perform basic and instrumental activities of daily living was found.
      CONCLUSION: The evolution of hip fracture in the year following it is related to
      high mortality and to a decrease in functional ability, with age and male sex
      being the factors associated with a worse prognosis, emphasizing the need for
      special follow-up care of these groups during the immediate and late
      postoperative periods.

PMID- 17187092
TI  - Anatomical variations in the human sinuatrial nodal artery.
AB  - OBJECTIVE: To analyze the anatomical variations of sinuatrial nodal branch(es) of
      the coronary artery mainly regarding their number; a recent report from Japan
      claims the presence of 2 branches in up to 50% of cases, an occurrence that would
      permit adequate flow compensation in case of occlusion or section of 1 of these
      branches. METHODS: The sinuatrial nodal branch(es) of 50 human hearts fixed in
      formol solution were dissected with the aid of a Normo Health 3.0 degree visor
      magnifying lens, measured, and classified as to the origin, route, and number of
      branches. RESULTS: In 94% (n = 47) of cases, a single sinuatrial nodal branch was
      found. classified: (A) two right side types, R1 (in 46% of cases, n = 23),
      situated medial to the right auricle and R2 (in 4% of cases, n = 2), situated on
      the posterior surface of the right atrium; (B) three left side types, L1 (in 24%
      of cases, n = 12), situated medial to the left auricle, L2 (in 16% of cases, n =
      8), situated posterior to the left auricle, and L3 (in 4% of cases, n = 2),
      situated on the posterior surface of the left atrium. Except for R2, each type
      was subdivided into 'a' or 'b' types, according to whether the sinuatrial nodal
      branch(es) occurred in a clockwise or counterclockwise orientation around the
      base of the superior cava vena. In 4% of cases (n = 2), 2 sinuatrial nodal
      branch(es) were observed with 1 branch originating from each of the coronary
      arteries. In 1 case (2%), 3 sinuatrial nodal branch(es) were found, 2 from the
      right coronary artery and the third probably from the bronchial branch of the
      thoracic aorta. In 30% of the cases, the sinuatrial nodal branch(es) formed a
      ring around the base of the superior cava vena. In all cases, the sinuatrial
      nodal branch(es) supplied collateral branches to the atrium and/or the auricle of
      the same side as its origin and/or to the opposite side. CONCLUSION: The low
      frequency of 2 sinuatrial nodal branch(es) in Brazilian individuals, compared to
      the higher frequency found among the Japanese, is probably due to a variation
      associated with ethnic group origin.

PMID- 17187091
TI  - Analysis of the risk factors for incidental carcinoma of the prostate in patients
      with benign prostatic hyperplasia.
AB  - PURPOSE: To determine the occurrence of incidental carcinoma of the prostate, its
      characteristics, and the risk factors for this diagnosis in a group of patients
      surgically treated for benign prostatic hyperplasia. METHODS: The study comprised
      a retrospective analysis of 218 patients. After surgical treatment, patients with
      the finding of incidental carcinoma of the prostate were compared to those
      without this finding. The preoperative variables analyzed were patient age,
      digital rectal examination, PSA, PSA density, prostate volume, and preoperative
      prostate biopsy. We also determined the sensitivity, specificity, positive
      predictive value, and negative predictive value of digital rectal examination and
      PSA for the finding of incidental carcinoma of the prostate at surgical specimen
      analysis. RESULTS: Thirteen (6.2%) out of the 218 patients presented incidental
      carcinoma of the prostate. Eight (61.5%) of these tumors were classified as T1a
      and 5 (38.5%) as T1b. Only advanced age (P = 0.003) and the presence of a suspect
      digital rectal examination (P = 0. 016) were statistically related to the
      findings of the surgical specimen analysis. The sensitivity, specificity,
      positive predictive value, and negative predictive value for the diagnosis of
      incidental carcinoma were 23.0%, 96.6%, 30.0%, and 95.2% for a suspect digital
      rectal examination and 85.0%, 34.1%, 7.5%, and 97.2% for a PSA greater than 4.0
      ng/mL. The accuracy for these methods was 92.2% and 37.1%, respectively.
      CONCLUSIONS: Advanced age and the presence of a suspect digital rectal
      examination represent the most important risk factors for the diagnosis of an
      incidental carcinoma of the prostate. However, the low positive predictive values
      reflect the weak correlations among these variables.

PMID- 17187093
TI  - Experimental pleurodesis induced by antibiotics (macrolides or quinolones).
AB  - PURPOSE: Chemical pleurodesis is a therapeutic tool for the treatment of
      recurrent pleural effusions, mainly those of neoplastic etiology. In the past,
      tetracycline was the sclerosant agent of choice in clinical practice, but
      presently, there is no consensus about an ideal agent. The aim of this study was
      to evaluate the effectiveness of macrolides (azithromycin and clarithromycin) or
      quinolones (levofloxacin and gatifloxacin) in inducing experimental pleurodesis
      in rabbits. METHOD: Forty New Zealand rabbits randomized into groups of 10
      received (at a total volume of 2 mL for each animal) 1 of the 4 drugs by
      intrapleural injection. After 28 days, the animals were euthanized and the
      pleural cavity was evaluated macroscopically and microscopically. RESULTS: The
      intensity of the macroscopic adhesions was mild in all groups. On microscopic
      analysis, minimal pleural fibrosis and inflammation were observed in all animals.
      CONCLUSION: The macrolides (azithromycin or clarithromycin) and the quinolones
      (levofloxacin or gatifloxacin) when injected into the normal pleural space of
      rabbits are not effective in promoting pleurodesis. Additional research is
      required to identify sclerosing agents capable of inducing pleurodesis.

PMID- 17187094
TI  - Comparative study of cryopreserved bone tissue and tissue preserved in a 98%
      glycerol solution.
AB  - OBJECTIVE: To compare the bone graft cryopreservation method (at -80 degrees C)
      with a preservation method using a 98% glycerol solution at room temperature (10
      degrees C-35 degrees C), by testing the antibacterial and fungal effects of 98%
      glycerol and comparatively analyzing the observed histological changes resulting
      from the use of both methods. METHOD: This study was of 30 samples of trabecular
      bone tissue from 10 patients undergoing total hip arthroplasty. Each femoral head
      provided 3 samples that were randomized into 3 groups, namely, the control group,
      the cryopreserved group, and the group preserved in a 98% glycerol at room
      temperature for 1 year. The samples were submitted to histomorphologic, cell
      feasibility, and microbiologic analyses. The results were statistically analyzed
      using the McNemar test, with a statistical significance index of 0.05. RESULTS:
      Values obtained using the McNemar test to compare probability distributions of
      histomorphologic variables (mature or lamellar bone, immature bone, and necrosis)
      and cell feasibility (osteoblasts and osteoclasts) indicated that there is no
      difference between the distributions of variables under the 3 experimental
      conditions. Microbiological analysis of the 98% glycerol solution and bone
      fragments from samples stored for 1 year at room temperature did not show
      bacterial or fungal growth. The histological and microbiological investigation
      were performed at 2 different time points: immediately after the sample
      processing and after 1 year. CONCLUSION: The method used to preserve bone grafts
      kept in 98% glycerol at room temperature (10 degrees C-35 degrees C) was similar
      to cryopreservation in terms of bone matrix preservation; no bacteria or fungi
      were found in the samples.

PMID- 17187095
TI  - Complex wounds.
AB  - Complex wound is the term used more recently to group those well-known difficult
      wounds, either chronic or acute, that challenge medical and nursing teams. They
      defy cure using conventional and simple "dressings" therapy and currently have a
      major socioeconomic impact. The purpose of this review is to bring these wounds
      to the attention of the health-care community, suggesting that they should be
      treated by multidisciplinary teams in specialized hospital centers. In most
      cases, surgical treatment is unavoidable, because the extent of skin and
      subcutaneous tissue loss requires reconstruction with grafts and flaps. New
      technologies, such as the negative pressure device, should be introduced. A brief
      review is provided of the major groups of complex wounds--diabetic wounds,
      pressure sores, chronic venous ulcers, post-infection soft-tissue gangrenes, and
      ulcers resulting from vasculitis.

PMID- 17187096
TI  - Antidepressant-induced hyponatremia.

PMID- 17187097
TI  - Palindromic rheumatism associated with primary hypertrophic osteoarthropathy.

PMID- 17187098
TI  - Implementation of the national policy to reduce accidents and violence.

PMID- 17187099
TI  - [Old and new risks: In pursuit of other forms of protection].
AB  - Based on the concept of health as openness to risk, as outlined by Canguilhem in
      1946, the authors seek to distinguish between risks that require social
      protection networks and those that should be tolerated as part of the human
      condition. To understand this issue, the article analyzes the historical
      emergence of the risk concept as viewed in early industrial society and its link
      to the idea of dangerousness and risk as analyzed by Robert Castel in his work
      From Dangerousness to Risk and L'Insegurite Sociale: Qu'est-ce Qu'etre Protege?
      The authors discuss the continuities and discontinuities in these classical
      risks, with their social protection structures, and the emerging awareness of
      multiple hazards in late modernity.

PMID- 17187100
TI  - [The effect of folic acid fortification on the reduction of neural tube defects].
AB  - Neural tube defects are congenital malformations that occur during initial fetal
      development, leading to anencephaly and spina bifida; folic acid deficiency is
      the most important risk factor identified to date. Brazil has one of the world's
      highest neural tube defect rates. Food consumption surveys among pregnant
      Brazilian women showed a high rate of inadequate folic acid intake (< 0.6
      mg/day). In 2004, the National Health Surveillance Agency (ANVISA) mandated the
      fortification of corn meal and wheat flour with folic acid (0.15 mg/100g). The
      National Family Budget Survey estimated the average amount of bread/flour
      products available in households as 106.1g/day (contributing with 0.16 mg folic
      acid/day). However, while in the South of the country the supply was 144 g/day,
      in the North and Central West it barely reached 70 g/day. Folic acid food
      fortification is mandatory in some 40 countries, but only four have assessed this
      strategy. The existing studies have all shown a significant impact, ranging from
      19 to 78%. Folic acid fortification is an undeniably important intervention for
      primary prevention, and neural tube defects can now be considered a preventable
      epidemic.

PMID- 17187101
TI  - HIV-1 seroprevalence in the general population of Salvador, Bahia State,
      Northeast Brazil.
AB  - To estimate HIV-1 seroprevalence in the general population of Salvador, Bahia,
      Brazil, we conducted a cross-sectional survey of 3,437 residents from 1998 to
      2000. Subjects were drawn from 30 sentinel areas representing a wide range of
      living conditions. Plasma samples were screened for HIV-1 antibodies by ELISA and
      confirmed by immunofluorescent assay. Subtype determination by HMA was performed
      after proviral DNA amplification. Phylogenetic analysis using parsimony was
      performed with the neighbor-joining method. Overall HIV-1 seroprevalence was
      0.55% (19/3,446): 0.8% for men and 0.36% for women. Seroprevalence was higher in
      the 31-45-year age group (1%) and among persons with family income less than
      twice the minimum wage (0.78%) as compared to 0.33% for the higher income group.
      Syphilis was detected in 37% of HIV seropositive individuals. Phylogenetic
      inferences identified 10 samples as subtype B in the env region and 2 samples
      with Benv/Fgag/Fpol and Fenv/Bgag. Age > or = 30 years, male gender, and income <
      or = 2 times the minimum wage were identified as risk factors for HIV-1
      infection. Extrapolating the proportion of seropositive individuals to Salvador,
      the number of HIV-1 infected individuals was estimated at 13,750.

PMID- 17187102
TI  - Partial recording protocols for periodontal disease assessment in epidemiological
      surveys.
AB  - The objective of the present study was to compare the reliability of four partial
      mouth protocols for assessing shallow, moderate, and deep sites for periodontal
      pocket depth and clinical attachment levels. Periodontal pocket depth and
      clinical attachment level measurements were recorded for 156 subjects (age > or =
      30). The four models of partial-mouth protocols compared were: Model I: all sites
      per tooth in the random half-mouth protocol randomly selecting one maxillary and
      mandibular quadrant, Model II: buccal sites in a full-mouth protocol, Model III:
      buccal sites in the random half-mouth protocol randomly selecting one maxillary
      and mandibular quadrant, Model IV: all sites per tooth using Community
      Periodontal Index teeth. In comparison with full mouth examination, Model I did
      not show significant differences for periodontal pocket depth and clinical
      attachment level parameters. Models II and III were different for some
      periodontal pocket depth means, and Model IV significantly overestimated all
      clinical parameters related to periodontal disease. Model I appears to be
      adequate to substitute for the full-mouth examination to assess the prevalence
      and severity of chronic periodontal disease in adults.

PMID- 17187103
TI  - Factors associated with safe sex among public school students in Minas Gerais,
      Brazil.
AB  - A cross-sectional study was conducted to evaluate factors associated with safe
      sex among sexually active public school students in Minas Gerais State, Brazil.
      The study focused on correlations between the variables gender, age, schooling,
      current grade, ethnicity, religion, importance attributed to religion, mothers'
      education, prior exposure to any sex education, promotion of juvenile
      protagonism, and participation by health professionals in school activities and
      consistent condom use with casual or stable partners and with use of other modern
      contraceptive methods. Bivariate and multivariate logistic regression analyses
      were used. Male gender and participation by health professionals in school
      activities were positively associated with all indicators of safe sex, and
      maternal schooling of more than eight years was positively associated with
      consistent condom use with casual and stable partners. Secondary (versus
      elementary) schooling and age (older) were inversely associated with consistent
      condom use with casual and stable partners, respectively. Ascribing greater
      importance to religion and Evangelical religion were negatively associated with
      use of modern contraceptives in the last sexual intercourse.

PMID- 17187104
TI  - Assessing the physical violence component of the Revised Conflict Tactics Scales
      when used in heterosexual couples: An item response theory analysis.
AB  - Although there are psychometric evaluations of the Revised Conflict Tactics
      Scales (CTS2) when applied to heterosexual relationships, none has used item
      response theory (IRT). To address this gap, the present paper assesses the
      instrument's physical violence subscale. The CTS2 was applied to 764 women who
      also responded for their partners. Single dimensionality assumption was
      corroborated. A 2-parameter logistic IRT model was used for estimating location
      and discriminating power of each item. Differential item functioning and item
      information pattern along the violence continuum were assessed. Gender
      differences were detected in 3 out of 12 items. Item coverage of the latent trait
      spectrum indicated little information at the lower ends, while plenty in the
      middle and upper ranges. Still, depending on gender, some item overlaps and
      regions with gaps could be detected. Despite some unresolved problems, the
      analysis shows that the items form a theoretically coherent information set
      across the continuum. Provided the user is aware of possible drawbacks, using the
      physical violence subscale of the CTS2 in heterosexual couples is still a
      sensible option.

PMID- 17187105
TI  - [Translation, adaptation, and validation of the Brazilian version of the
      Marijuana Expectancy Questionnaire].
AB  - This study presents the translation and validation of the Marijuana Expectancy
      Questionnaire (MEQ-Brazilian Adaptation), which evaluates the expectancy of
      results in marijuana use, important for treatment and prognosis related to
      addiction to this substance. The sample consisted of 400 subjects, 217 males and
      183 females, of whom 147 were marijuana users and 253 were non-users. In the user
      group, 90 subjects were marijuana-dependent. Semantic validation of the MEQ
      Brazilian Adaptation was confirmed after evaluation and suggestions by an expert
      review panel. In the Brazilian sample, 78 items were applied; however, the
      decision was made for a statistical analysis using the reduced scale (55 items),
      with similar psychometric properties. For both scales, an alpha = 0.89 was
      obtained. Discriminant validation of the reduced scale was statistically
      significant (p = 0.001). Temporal stability was examined using a 123-subject
      sample with a one-week interval between test and retest, indicating that the
      instrument obtains a consistent response pattern over time (r = 0.990). MEQ
      Brazilian Adaptation presented good psychometric results and can be used in
      studies that aim to evaluate expectancy of results related to marijuana use.

PMID- 17187106
TI  - [Conflicting situations in the reception of oral health teams from the Family
      Health Program in Alagoinhas, Bahia, Brazil].
AB  - The study discusses the conflicting situations that arise while receiving oral
      health teams in Alagoinhas, Bahia, Brazil. The main orientation for the Family
      Health Program is based on analyzing health care work flowcharts. The current
      qualitative research used semi-structured interviews and practical observation as
      the data collection techniques. There were 17 study subjects: group I (dentists
      and dental assistants - 6); group II (other health workers - 6); and group III
      (users - 5). Users' first contact with the family health team is in the
      reception, often in a tense and conflicting atmosphere, but with the potential
      for alternatives for change, as a privileged space for the use of low-key
      technologies. The therapeutic process varies: e.g. clinical consultation,
      emergency care, scheduled follow-up, and referral to other health services in the
      system. However, oral health teams conduct the reception process in different
      ways, depending on the practitioners' commitment and unique characteristics.

PMID- 17187107
TI  - [Standardization of conditions for PCR detection of Leishmania spp. DNA in sand
      flies (Diptera, Psychodidae)].
AB  - The correct identification of etiological agents in vector insects is crucial for
      epidemiological studies. Identification of flagellates in such vectors, usually
      by dissection of the digestive tract and microscopic observation of the contents
      as well as attempts at parasite isolation from insects in culture media, have
      proven operationally inadequate and with poor diagnostic specificity, since
      female sand flies are also hosts for other flagellates like Trypanosoma and
      Endotrypanum. Due to the efficiency and specificity of DNA target sequence
      amplification by polymerase chain reaction (PCR), the latter could be used to
      investigate the presence of Leishmania in sand flies, although the insects need
      to be properly stored and the Leishmania DNA extracted using appropriate
      methodology. This paper describes methodologies to standardize sand fly storage
      and Leishmania DNA extraction in such specimens as a more practical method in
      field studies.

PMID- 17187108
TI  - [Quality assessment of antibiotic prescriptions dispensed at public health units
      in Belo Horizonte, Minas Gerais, Brazil, 2002].
AB  - Overuse of antibiotics is a public health problem and has raised discussions
      concerning their rational use. This cross-sectional study focuses on the use of
      systemic antibiotics under the Belo Horizonte Municipal Health Department, Minas
      Gerais, Brazil, evaluating prescriptions dispensed in March 2002, based on WHO
      indicators for antibiotic use. On average, 20% of prescriptions dispensed
      involved at least one systemic antibiotic, among which approximately 46%
      originated from health care facilities not belonging to the municipal system
      itself. Amoxicillin was the most frequently prescribed antibiotic, followed by
      benzathine penicillin. Recording of technical data (dose, intervals between
      doses, administration, and treatment period) varied from 23.6 to 99.6%. Some 10%
      of prescriptions failed to specify the treatment period. The study showed the
      need for rules to allow quality improvement of antibiotic prescriptions, assuring
      the rational use of such medication by municipal health services.

PMID- 17187109
TI  - [Psychological distress among civilian police: A gender-based analysis].
AB  - This study aimed to investigate potential psychological distress among members of
      the civilian police force, based on gender differences. It analyzes data from
      previous research on work, health conditions, and quality of life in the civilian
      police using both quantitative and qualitative methods. The study included and
      tested data from the questionnaire applied to a statistically representative
      sample of 2,746 civilian police (80.8% males and 19.2% females) from the city of
      Rio de Janeiro, Brazil, according to gender variables and position in the police
      force (administrative, technical, and operational law enforcement). The study
      presents an overview of social and economic characteristics, job conditions,
      health problems, and quality of life, highlighting the areas of information where
      gender appears as an important factor. The Self-Reported Questionnaire (SRQ-20)
      was used to investigate psychological distress comparing males and females. The
      results did not show gender differences in psychological distress, but did
      identify significant differences in some items in the scale. Female police,
      especially in technical positions, showed a higher proportion than males. The
      conclusions corroborate some previous research.

PMID- 17187110
TI  - [The Unified National Health System and the third sector: Characterization of non
      hospital facilities providing basic health care services in Belo Horizonte, Minas
      Gerais, Brazil].
AB  - In Brazil, nonprofit or charitable organizations are the oldest and most
      traditional and institutionalized form of relationship between the third sector
      and the state. Despite the historical importance of charitable hospital care,
      little research has been done on the participation of the nonprofit sector in
      basic health care in the country. This article identifies and describes non
      hospital nonprofit facilities providing systematically organized basic health
      care in Belo Horizonte, Minas Gerais, Brazil, in 2004. The research focused on
      the facilities registered with the National Council on Social Work, using
      computer-assisted telephone and semi-structured interviews. Identification and
      description of these organizations showed that the charitable segment of the
      third sector conducts organized and systematic basic health care services but is
      not recognized by the Unified National Health System as a potential partner, even
      though it receives referrals from basic government services. The study showed
      spatial and temporal overlapping of government and third-sector services in the
      same target population.

PMID- 17187111
TI  - [Socioeconomic context and perceived oral health in an adult population in Rio de
      Janeiro, Brazil: A multilevel analysis].
AB  - One of the main limitations of the ecological design is aggregation bias. The
      problem can be addressed by designs that use small contextual hierarchical units
      with internal homogeneity. This study aimed to compare different geographic data
      structures in order to explore contextual effects of socioeconomic variables on
      the odds of perceived poor oral health. The analyses were based on a mixed design
      that included data from civil servants participating in the "Pro-Saude" censuses
      I and II and residing in the city of Rio de Janeiro, Brazil, in 1999 (n = 2,426);
      contextual data were obtained from the National Demographic Census conducted in
      1991. We used the variance partition coefficient to compare different geographic
      hierarchical structures. In this study, the smallest geographic partition (census
      tract) was the best unit for contextual analysis for studying variability in
      perceived poor oral health. Individual socioeconomic attributes explained more of
      the variance in perceived oral health than did the socioeconomic contexts of
      residential areas.

PMID- 17187112
TI  - [Fatherhood: The male experience from a gender focus].
AB  - Pregnant and postpartum women frequently complain about the limited involvement
      of their partners with their children, beginning in pregnancy. The current study
      thus aimed to understand men's feelings towards fatherhood during this period of
      their lives. The research adopted a qualitative approach and a gender-theory
      focus. The universe included men whose children were being treated at a pediatric
      outpatient clinic, and data were collected through semi-structured home
      interviews. Subjects' testimony was analyzed using discourse analysis, the basic
      principle of which is to recognize the most abstract levels of the text,
      identified by themes organized in blocks of meaning and allowing the construction
      of empirical categories. Study subjects' social position towards fatherhood shows
      that the model that men assume as father-providers coexists with that of the man
      who seeks to be a "new father", whose affective bond with the son or daughter
      begins during pregnancy, thus representing a break with traditional fatherhood.

PMID- 17187113
TI  - [Nutritional rehabilitation of undernourished and nutritionally at-risk children
      admitted to a supplementary food program in Mogi das Cruzes, Sao Paulo, Brazil].
AB  - This study aimed to evaluate the nutritional rehabilitation of undernourished
      children admitted to a program entitled Incentives to Fight Nutritional
      Deficiencies (ICCN) in Mogi das Cruzes, Sao Paulo, Brazil. The study included 724
      children (6 to 24 months old) from July 1999 to July 2001. The indices used to
      evaluate baseline nutritional status were weight-for-age, weight-for-length, and
      length-for-age, defining normal as z score > or = -1, at-risk as > or = -2 and < 
      1, moderate malnutrition as < -2 and > -3, and severe malnutrition as < or = -3.
      Nutritional evolution was evaluated using the length-for-age index, and the
      results were analyzed considering the average z score variation at the end of the
      12-month program. After 12 months, nutritional status had improved in all
      categories, while the best results were in children with more intense baseline
      nutritional deficiency. Gains in length were 1.12, 0.82, 0.57, and 0.45 z scores
      for the severe and moderate malnutrition, nutritional risk, and normal
      categories, respectively. The ICCN in Mogi das Cruzes thus demonstrated effective
      nutritional improvement for program beneficiaries.

PMID- 17187114
TI  - [Early neonatal mortality: An analysis of multiple causes of death by the Grade
      of Membership method].
AB  - This population-based study aimed to determine the profile of early neonatal
      deaths in Belo Horizonte, Minas Gerais, Brazil, from 2000 to 2003. Profiles were
      analyzed from the perspective of avoidability, justified by persistently high
      early neonatal mortality rates in the city. Three profiles were generated for
      multiple causes of death from the perspective of fuzzy sets, using the Grade of
      Membership method. Birth weight and the hospital's corporate status were also
      related to the three profiles. Private hospitals were characterized by so-called
      "difficult-to-prevent deaths, with mention of congenital malformations" (profile
      2). The Unified National Health System (SUS) generated two distinct profiles.
      Private maternity facilities contracted out by the SUS showed "preventable
      deaths" (profile 1), while "premature deaths" (profile 3) occurred in the public
      Federal and State maternity hospitals. This typology highlights the need to adopt
      differential policies in the SUS, focusing on evaluation and accreditation for
      maternity facilities contracted out by the SUS and--for the system as a whole--on
      the routine adoption of protocols for childbirth care and prophylactic measures
      that are known to reduce neonatal morbidity and mortality.

PMID- 17187115
TI  - [Pharmacovigilance implementation and operational conditions in the
      pharmaceutical industry in Sao Paulo State, Brazil].
AB  - The development of new drugs and limitations of clinical trials have increased
      the likelihood of adverse drug events. Pharmacovigilance is essential to detect
      and evaluate adverse drug events, thereby reducing risks and avoiding excessive
      public health costs. This study focused on the pharmacovigilance programs in the
      pharmaceutical industry in Sao Paulo State, Brazil. Data were collected through
      questionnaires sent electronically to 105 companies, 41.9% of which responded.
      The main reason for implementing pharmacovigilance programs was to comply with
      legal requirements, while the main justification for its absence was production
      limited to herbal remedies, officinal products, and supplements. The article
      discusses the obstacles to program implementation, resources used, and
      characteristics of several such programs. CONCLUSIONS: (a) standardization is the
      reason for the increasing number of programs and reports, but more specific
      guidelines are needed; (b) results depend on multi-sector involvement; (c)
      customer service centers are an important source of reports; and (d) operation of
      the service requires only modest human and material resources.

PMID- 17187116
TI  - [Teenage pregnancy: Behavioral and socio-demographic profile of an urban
      Brazilian population].
AB  - To identify the socio-demographic behavioral profile of low-income pregnant
      teenagers, 1,000 adolescents admitted to a Brazilian public maternity hospital
      from July 24, 2001, to November 27, 2002, were interviewed. Socio-demographic and
      behavioral variables were assessed through a questionnaire. Over the 492 days of
      the study, 24.3% of admissions were adolescents (930 for childbirth and 70 for
      miscarriage). Mean maternal age was 17 years. Most teenagers (72.9%) lived near
      the hospital. 930 (93%) belonged to socioeconomic classes C, D, and E. School
      dropout was identified in 67.3% of the total. 80.1% of the subjects were giving
      birth for the first time. 81.2% had not planned the pregnancy, and 23.8% had been
      using some contraceptive method. 67.4% had vaginal deliveries. Some 13.3% of the
      newborns were premature and 15.9% had low birth weight. 17.3% of these adolescent
      mothers reported smoking during pregnancy, with 2.8% reporting alcohol and 1.7%
      illicit drugs. Teenage pregnancy is a complex phenomenon associated with various
      economic, educational, and behavioral factors. The study provides importance
      references for public policies to prevent teenage pregnancy.

PMID- 17187117
TI  - [Risk factors for orthotopic liver transplantation failure in Rio Grande do Sul,
      Brazil].
AB  - Risk factors for failure of liver transplantation from cadaveric donors were
      investigated in this retrospective study using data from medical records of
      patients in Rio Grande do Sul, Brazil, who were submitted to liver
      transplantation for the first time from January 1999 to July 2003 and were over
      15 years of age at the time of surgery. Some 13% of failures occurred in the
      first month, 11% from 2 to 12 months, and 5% after 12 months; 88% of failures
      resulted in death and 12% in retransplantation. In the multivariate models, rate
      ratios for failure were higher for total family income less than 10 times the
      minimum wage, recipient's age > 45 years, non-whites, high clinical risk, and
      donor's age > or = 56 years. Female gender showed an effect in the unadjusted
      model only. Special attention to patients at increased risk, with income support
      for those with low family income, and early diagnosis of the need for
      transplantation may improve the success of liver transplantation.

PMID- 17187119
TI  - [Psychiatric reform in a local context in Brazil: A qualitative analysis].
AB  - This study focuses on the daily institutional activities in a Center for
      Psychosocial Care (CAPS), a municipal mental health service in Andradas, Minas
      Gerais, Brazil. The study specifically analyzes the social representations by
      health care professionals regarding the social rehabilitation of their patients,
      vis-a-vis new proposals approved under the Brazilian psychiatric reform. The
      study adopts a historical and conjunctural analysis, based on the premise that to
      evaluate the new process of institutional intervention contributes to both its
      implementation and improvement. The study also focuses on the stance by health
      care professionals towards interdisciplinary work and the factors involved in
      this practice. A qualitative approach was used throughout the study.

PMID- 17187118
TI  - [Behavior associated with HIV and HCV infection in female prison inmates in Sao
      Paulo, Brazil].
AB  - An increase has been observed in AIDS and hepatitis C cases in women, including
      female prison inmates. This study focused on inmates' behavioral factors
      associated with risk of HIV and HCV transmission in a women's detention facility
      in Sao Paulo, Brazil. Behavioral questionnaires were applied and HIV and HCV
      serology were performed. The selected measure of association was odds ratio for
      both the bi and multivariate logistic regression analyses. 290 inmates
      participated in the study. HIV and HCV prevalence rates were 13.9% and 16.2%,
      respectively. Statistically significant associations were observed (p < 0.05)
      between HIV and the following variables: partner with AIDS OR = 6.9 (2.7-35.2);
      injection drug users (IDU) OR = 3.3 (1.6-14.7); regular partner OR = 3.7 (1.5
      8.3), and between HCV and: IDU OR = 13.7 (4.4-42.7); IDU partner OR = 4.9 (1.9
      12.2); previous arrest OR = 2.8 (1.2-6.5) adjusted for: partner with AIDS, IDU,
      IDU partner, drug user, and previous arrest. In conclusion, parenteral risk was
      associated with HIV and HCV infection and sexual risk with HIV. Appropriate and
      continuous preventive programs are recommended in the prison.

PMID- 17187120
TI  - [Prevalence and factors associated with hospital admissions in a population-based
      study in a southern Brazilian city].
AB  - This cross-sectional study investigates the use of health services and associated
      factors in individuals > or = 14 years of age in Canoas, Rio Grande do Sul,
      Brazil. 1,954 persons were interviewed in 40 census tracts. One-year prevalence
      of hospital admissions was 9.4%. Adjusted data analysis showed that
      hospitalization was associated with: age > or = 60 years (RP = 4.14; 95% CI: 2.07
      8.25), physician visit in the previous two months (RP = 2.79; 95%CI: 2.03-3.83),
      and > or = 2 stressful life events (RP = 1.83; 95%CI: 1.19-2.80). Individual
      income of > or = 2.10 times the prevailing minimum wage was associated with
      decreased likelihood of hospitalization (RP = 0.60; 95% CI: 0.41-0.87).
      Prevalence of hospital admissions was consistent with other studies. Higher
      prevalence of hospitalization in lower-income groups may indicate decreased
      access to primary health care. Other possible factors are higher morbidity and
      severity of diseases among lower-income groups. Future research should focus on
      the relationship between morbidity and stressful life events.

PMID- 17187122
TI  - [Preliminary analysis of the Information System in the Brazilian Schistosomiasis
      Control Program, 1999-2003].
AB  - This study provides a preliminary analysis of the Information System in the
      Schistosomiasis Control Program (SISPCE) in the States of Bahia, Sergipe,
      Alagoas, and Pernambuco, Brazil, from 1999 to 2003. The data analysis suggests a
      sharp decline in data entry in the system during the transition period involving
      health services decentralization, followed by a gradual increase. Major under
      recording was observed in Pernambuco. SISPCE-DATASUS and IBGE (National Census
      Bureau) data are insufficient to construct a surveillance index for serious forms
      of the endemic disease and other aspects that could relate sanitary conditions to
      schistosomiasis. Reformulation of the SISPCE is key for schistosomiasis control
      measures, given the new reality in the Brazilian health system. The data system
      should be redesigned in order to integrate the health policies with the Unified
      National Health System's guidelines, using a systematic data collection
      methodology in keeping with local specificities and allowing prospective
      comparisons and evaluations, in addition to constructing new indicators with an
      emphasis on morbidity and determinants of the endemic and the adoption of
      analytical of the that express the real situation of the schistosomiasis in the
      States.

PMID- 17187121
TI  - [Adolescent males and sex life: Heterogeneous motivations related to sexual
      debut].
AB  - This article describes male adolescents' affective history and reasons for
      initiating or postponing sexual activity, using interviews with 184 males ages 15
      to 19 and residing in the city of Sao Paulo, Brazil, in 2002. Factors for sexual
      debut included physical attraction, curiosity, and the desire to lose their
      virginity, suggesting a profile similar to the male social role. Most of the
      virgin adolescent males justified their choice based on issues of a romantic
      order, such as not having found the right person or because they preferred to
      remain virgin until marrying. The results showed a dual social pattern, valuing
      the feeling of love and deliverance to the loved one, simultaneously with the
      pressing physical and instinctive desire for sex. Traditional patterns of
      masculinity, like the dissociation between sex and love, appear to be transposed
      to sexual debut, revealing a diversity in the ways of experiencing sexuality
      during adolescence, related in turn to the sexual and reproductive health of men
      and their partners.

PMID- 17187123
TI  - [Comments on the paper by Rocha et al].

PMID- 17187124
TI  - [The cornea is not a bit of plastic].

PMID- 17187125
TI  - Retinal nerve fiber layer analysis using GDx in 49 patients with chronic phase
      DUSN.
AB  - PURPOSE: To describe retinal nerve fiber layer changes in late-stage diffuse
      unilateral subacute neuroretinitis eyes and compare these results with healthy
      eyes observed through nerve fiber analyzer (GDx). METHODS: This is a
      retrospective case-control study in which 49 eyes in late-stage diffuse
      unilateral subacute neuroretinitis were examined from May/97 to December/01.
      First, eyes with diffuse unilateral subacute neuroretinitis and healthy
      contralateral eyes (Control Group I) were statistically matched. Subsequently,
      eyes with diffuse unilateral subacute neuroretinitis were compared with eyes of
      healthy patients (Control Group II). RESULTS: Eyes from Control Groups I and II
      had higher relative frequency of "within normal limits" status. Eyes from the
      diffuse unilateral subacute neuroretinitis (DUSN) Group had higher frequency of
      "outside normal limits" and "borderline" status. Control Groups I and II had
      absolute values different from the DUSN Group regarding all parameters (p <
      0.05), except for Symmetry in Control Groups I and II, Average thickness and
      Superior Integral in control group II. CONCLUSION: Patients with late-stage
      diffuse unilateral subacute neuroretinitis presented presumed decrease in nerve
      fiber layer thickness shown by GDx. Retinal zones with larger vascular support
      and larger amount of nerve fibers presented higher decrease in the delay of the
      reflected light measured by the nerve fiber analyzer.

PMID- 17187126
TI  - Visual field (Octopus 1-2-3) in normal subjects divided into homogeneous age
      groups.
AB  - PURPOSE: To determine the values in decibels of retinal sensitivity within the
      central 26 degrees of the visual field of normal subjects divided into homogenous
      age groups using the Octopus 1-2-3; to compare the values of retinal sensitivity
      we have found with those considered normal in the statistical package obtained by
      a multicenter study performed in 1994 with Octopus 201. METHODS: 181 subjects
      divided into 6 homogeneous age groups (10 to 19 yr; 20 to 29 yr; 30 to 39 yr; 40
      to 49 yr; 50 to 59 yr and 60 year-old or older) were evaluated. Data on visual
      sensitivity and age, average sensitivity of central and paracentral regions and
      eccentricity were calculated. RESULTS: The average visual sensitivity of all
      groups was 26.77 +/- 1.74 dB. Correlation between visual sensitivity and age
      evaluated by linear regression was 28.4 - 0.040 x (age) for the whole sample and
      28.7 - 0.050 x (age) for subjects aged 20 or more. Sensitivity reduction by
      eccentricity was -0.30 dB/degree for the whole sample and for subjects aged 20 or
      more. CONCLUSIONS: Correlation between retinal sensitivity values and age based
      on the autoperimeter Octopus 201 (average sensitivity of 31.2 - 0.064 x age) is
      different from that found in this study: average sensitivity of 28.4 - 0.040 x
      (age) for the whole sample; 28.7 - 0.050 x (age) for subjects aged 20 or more.
      Values obtained with the Octopus 1-2-3 autoperimeter cannot be compared with
      those by other Octopus models (101, 201 and 500) due to their distinct features.

PMID- 17187127
TI  - [Effects of metoclopramide-induced hyperprolactinemia on the murine corneal].
AB  - PURPOSE: To evaluate the morphological changes in murine cornea upon
      metoclopramide-induced hyperprolactinemia during the proestrous phase or
      pregnancy. METHODS: Forty adult mice were divided into two groups: (control) CTR1
      and (treated with metoclopramide (MET1). After fifty days, half of the mice were
      sacrificed. The remaining animals were mated, and then labeled as pregnant
      controls (CTR2). Part of these animals were treated with metoclopramide and
      constituted the metoclopramide-treated pregnant (MET2) group. The groups CTR2 and
      MET2 were sacrificed on the 6th day of pregnancy. The hormonal levels were
      assessed by chemioluminescence and radioimmunoassay methods and the cornea was
      removed for the histomorphometric study. RESULTS: The epithelial, stromal,
      endothelial and total thickness in the experimental group was: MET1 and MET2 were
      higher than one in the control group: CTR1 and CTR2. There was a significant
      reduction of the hormonal level in the animals that received metoclopramide as
      compared to controls (CTR1: estradiol = 156.6 +/- 42.2 pg/ml; progesterone = 39.4
      +/- 5.1 ng/ml; prolactin = 130.4 +/- 26.2 ng/ml; MET1: estradiol = 108.0 +/- 33.1
      pg/ml; progesterone = 28.0 +/- 6.4 ng/ml; prolactin = 551.5 +/- 23.3 ng/ml; CTR2:
      estradiol = 354.0 +/- 56.0 pg/ml; progesterone = 251.0 +/- 56.0 ng/ml; prolactin
      = 423.2 +/- 28.1 ng/ml; MET2: estradiol = 293.0 +/- 43.0 pg/ml; progesterone =
      184.0 +/- 33.0 ng/ml; prolactin = 823.1 +/- 51.1 ng/ml). CONCLUSION: The
      metoclopramide-induced hyperprolactinemia may increase corneal layers, mainly in
      pregnant mice. Possibly, this effect is related to reduction in estrogen and
      progesterone production.

PMID- 17187128
TI  - [Blepharoptosis in contact lens wearers].
AB  - PURPOSE: To investigate the occurrence of acquired blepharoptosis in contact lens
      wearers. METHODS: Prospective analysis of 50 contact lens wearers being followed
      at the Contact Lenses Section of the Ophthalmology Service at the "Complexo
      Hospitalar Santa Casa de Porto Alegre" between April and November 2004. The
      margin reflex distance (MRD) was evaluated for the 99 eyelids of contact lens
      wearers and for the 52 eyelids of controls. A patient whose measurement was less
      than 2 mm or with an assymetry of margin reflex distance greater or equal to 2 mm
      were considered with blepharoptosis. The contact lens type and duration of
      contact lenses wear were evaluated. RESULTS: Five patients presented ptosis, all
      of them were hard contact lens wearers, one had bilateral and four had unilateral
      ptosis. The study shows that the contact lens wearers had the margin reflex
      distance 0.88 mm smaller than the non-wearers. The margin reflex distance values
      decreased progressively in the studied groups: controls, gelatinous contact lens
      wearers and rigid contact lens wearers. CONCLUSION: The study suggests that
      contact lens wearers have alterations in the margin reflex distance values,
      especially the rigid contact lens wearers.

PMID- 17187129
TI  - [The influence of intraocular pressure reduction with medication on retinal nerve
      fiber layer thickness measurements obtained with scanning laser polarimetry in
      glaucomatous and hypertensive eyes].
AB  - PURPOSE: To evaluate changes in retinal nerve fiber layer thickness as measured
      by scanning laser polarimetry (SLP) after the use of medication to reduce
      intraocular pressure (IOP) in glaucomatous or ocular hypertensive patients.
      METHODS: The authors prospectively enrolled 37 eyes of 37 patients in whom IOP
      was reduced by more than 25% after the use of medication. The images were
      obtained before and 15 to 30 days after the introduction of medication. The SLP
      parameters measured before and after the use of medication were compared using
      paired Student's t Test. RESULTS: The mean IOP was significantly reduced from
      26.57 +/- 4.23 mmHg to 16.54 +/- 2.92 mmHg after the use of medication (p <
      0.05). None of the 10 SLP analyzed parameters was significantly affected by the
      reduction of IOP with medication (p > 0.05). CONCLUSION: The retinal nerve fiber
      layer thickness, as measured by SLP, is not affected by the reduction of IOP with
      medication in patients with glaucoma or ocular hypertension.

PMID- 17187130
TI  - [Major indications for corneal penetrating keratoplasty at a reference service in
      Sao Paulo state (Sorocaba - SP, Brazil)].
AB  - PURPOSE: To identify the main indications for corneal transplantation, analyze
      the results and provide demographic and epidemiological profile of patients
      referred to the Corneal Transplantation Project. METHODS: A retrospective
      analysis, from June to December 2003, of patients referred to the Corneal
      Transplantation Project. RESULTS: Total of 171 patients. One hundred and two
      (59.6%) patients were male and 69 (40.3%) female; mean age was 37 years. One
      hundred and six (49%) patients had indication for corneal transplantation. The
      origins of patients were: Sao Paulo (68%), Minas Gerais (6%), Parana (6%), Rio de
      Janeiro (5%), Maranhao (3%) and others (12%). The main indications: keratoconus
      65%, pseudophakic bullous keratopathy 21%, corneal scarring 10%, Fuchs dystrophy
      1.9%, lattice dystrophy 0.9% and Stevens-Johnson syndrome 0.9%. CONCLUSION: Many
      patients referred to corneal transplantation had no indication for such
      procedure. This fact demonstrates the poor knowledge of general ophthalmologists
      about the real indications of penetrating keratoplasty. Keratoconus was the major
      indication followed by pseudophakic bullous keratopathy.

PMID- 17187131
TI  - [Ocular findings in patients older than 99 years].
AB  - PURPOSE: To determine vision conditions and ocular findings in patients older
      than 99 years. METHODS: Patients were recruited by media advertisement and
      examined at the Vision Institute of UNIFESP. The following examinations were
      performed: visual acuity, ectoscopy, refraction, biomicroscopy, tear film break
      up time, Schirmer basal test, tonometry, direct and indirect ophthalmoscopy.
      Complementary examinations such as optical coherence tomography were performed
      when indicated. RESULTS: Thirty patients older than 99 years were identified.
      Mean age of 101.5+/-1.8, 25 females and 5 males. Most common systemic disease,
      according to history, was arterial hypertension. In 11 patients (55%), the best
      corrected far visual acuity was 20/100 or better. The best corrected near visual
      acuity was J4 or better also in 55% (11 patients) and 63.0% (7 patients) of these
      were the ones that had not been submitted to cataract surgery. The most frequent
      visual complaint was low vision for reading (55%) and other 8 patients (40%)
      reported no disturbance (satisfied with their vision). Lens opacity was present
      in 9 patients (60%) and 8 patients (40%) had previous cataract surgery (5 aphakic
      eyes, 9 pseudophakic eyes). Cataract was identified as important for impairment
      of vision in 5 patients but only 2 of them wanted to be submitted to surgery. The
      main cause of visual impairment was age-related macular degeneration, present in
      all patients, 95% with no exudative form. Vision improved with new refractive
      prescription in 4 patients. CONCLUSION: Once we understand the needs we can plan
      specific diagnostic and treatment strategies. This sample showed that most were
      female (83.3%), with good general health (35%), most with systemic arterial
      hypertension (40%), complaining of low vision for reading (55%) because of age
      related macular degeneration (100%, 95% dry form). Only 40% had been previously
      submitted to cataract surgery. Most of the patients with cataract said to be
      satisfied with their vision; of the 5 patients that could be operated only 2
      decided to do it. Low vision for reading, AMD and cataract were the main
      findings.

PMID- 17187133
TI  - [Blue-on-yellow perimetry in tobacco and alcohol consumers].
AB  - PURPOSE: To evaluate the visual field changes in blue-on-yellow perimetry (B/Y)
      strategy 10-2 in alcohol and tobacco smoking consumers. METHODS: Forty-two eyes
      of twenty-one users were studied. Fifteen individuals were used as a control
      group. All volunteers were males. After normal ophthalmologic examinations,
      central 10-2 (B/Y) was performed in both eyes. Analysis of the results was
      performed through the alterations in the depth graph defect and number of altered
      points. RESULTS: It was found that the majority of the chronic alcohol and
      tobacco smoking consumers had a greater frequency of alterations in the depth
      graph defect; 40 eyes (95.3%), (> 10 dB), and 27 eyes (64.3%) showed a number of
      altered points, (> 10 points), (p < 0.0001). All those who were used as a control
      group showed alterations in the depth graph defect and number of altered points,
      but had less than 10dB and 10 altered points, respectively. CONCLUSION: A higher
      number of abnormal points and depth graph defects and number of altered points
      were observed in alcohol and tobacco smoking consumers reflecting a higher number
      of alterations in the cells of the parvocellular system, responsible for color
      function, by B/Y perimetry.

PMID- 17187132
TI  - [Clear lens extraction: visual outcomes and vitreoretinopathy frequence].
AB  - PURPOSE: To evaluate visual results and vitreoretinopathy and retinal detachment
      frequencies in patients with and without prophylactic pre-equatorial retinal
      photocoagulation, who underwent clear lens extraction (CLE) to correct myopia.
      METHODS: Thirty-five patients (60 eyes) that underwent clear lens extraction at
      the "Fundacao Altino Ventura" had median follow-up of 20.5 months. They were
      classified into 3 groups: Group I that was submitted to preoperative 360 degrees
      preequatorial retinal photocoagulation; Group II that was submitted to
      prophylactic photocoagulation around predisposing lesions; and Group III that was
      not submitted to preoperative retinal photocoagulation. The presence of corrected
      visual acuity (CVA), refractional spherical equivalent (RSE) and choroidal
      neovascularization (CNV), predisposing lesions and retinal detachment (RD) was
      evaluated. RESULTS: Median corrected visual acuity value rose from 0.2 in the
      preoperative period to 0.5 in the postoperative period and refractional spherical
      equivalent decreased from -17SD to -1.7SD. There was no retinal detachment, but
      vitreous retinal traction areas appeared in 4 eyes (2 submitted to 360 degrees
      laser and 2 not submitted to laser) and 1 case of choroidal neovascularization
      also occurred. CONCLUSIONS: Clear lens extraction was an effective and
      predictable surgery to reduce myopias and an apparently safe procedure in
      patients with and without prophylactic preequatorial retinal photocoagulation. A
      longer follow-up in a larger group may validate its safety as a refractive
      surgery.

PMID- 17187134
TI  - [Exenteration: a retrospective study].
AB  - PURPOSE: To review all cases of orbit exenteration performed at the Orbit Sector,
      Ophthalmology Department - Federal University of Sao Paulo, from 1998 to 2003.
      METHODS: We reviewed conditions leading to orbital exenteration in 21 patients at
      the Orbit Sector of Unifesp-EPM from August 1998 to May 2003. Data regarding sex,
      age, race, primary lesion site, visual acuity at the moment of diagnosis,
      previous surgeries related to the exenteration, type of performed surgery,
      histopathologic diagnosis, postoperative complications and use of adjuvant
      treatment were collected. RESULTS: 21 patient charts were retrospectively
      analyzed. Ages ranged from 5 to 91 years (mean of 58.5 years). Of these, 12 were
      male and 9 were female, most of them Caucasian. All lesions that led to
      exenteration were malignant neoplasias; however, none were metastatic. Lesions
      originated from eyelids in twelve patients, from bulbar conjunctiva in six and
      from the orbit in three. Cases were also classified as squamous cell carcinoma
      (eleven cases), basal cell carcinoma (four cases), sebaceous gland carcinoma (two
      cases), rhabdomyosarcoma (two cases), mucoepidermoid carcinoma (one case) and
      adnexal microcistic carcinoma (one case). Visual acuity at the moment of
      diagnosis ranged from 20/40 to no light perception. Only six patients had been
      submitted to previous surgeries related to the exenteration. After surgery, three
      patients suffered graft necrosis, one presented ethmoidal sinus fistula to the
      orbit and one presented orbital socket shrinkage. Six patients needed
      postoperative radiotherapy and two had been previously submitted to chemotherapy.
      CONCLUSION: Most patients analyzed in our study presented lesions that are
      usually small in the beginning; however, they can disseminate to the orbit in the
      absence of adequate treatment.

PMID- 17187135
TI  - [Mitomicyn C eye drops as alternative treatment for pyogenic granuloma in
      anophthalmic socket].
AB  - PURPOSE: To evaluate the efficacy of mitomycin C eye drops 0.02% concentration
      (0.02% MMC) in pyogenic granuloma in anophthalmic socket. METHODS: Six patients
      who presented pyogenic granuloma were treated with 0.02% MMC four times a day in
      fifteen-day cycles with intervals of fifteen days between each cycle. The
      patients were observed every week. RESULTS: Among the six studied patients, one
      presented a complete resolution of the pyogenic granuloma after a ten-day
      treatment with 0.02% MMC that is, before the end of the first cycle. In two
      patients, the treatment was successful after two weeks using 0.02% MMC (one
      complete cycle). In other two patients, the resolution of the lesion occurred
      after five weeks that is, at the beginning of the second cycle. 0.02% MMC was not
      successful in only one patient whose lesion persisted after two cycles of the
      treatment. None of the patients presented complications after the use of 0.02%
      MMC. CONCLUSION: The topical use of 0.02% MMC proved efficacy in the treatment of
      anophthalmic socket pyogenic granuloma. A small number of patients took part in
      this study, therefore another randomized and comparative research is necessary in
      order to compare the efficacy of 0.02% MMC with other drugs such as
      corticosteroids and antimetabolites.

PMID- 17187136
TI  - [Visual rehabilitation in patients with retinitis pigmentosa].
AB  - PURPOSE: To determine which low-vision aids could be useful to patients with
      retinitis pigmentosa and also the benefits that the rehabilitation program could
      provide based on visual acuity and/or daily visual tasks. METHODS: A group of 30
      patients with retinitis pigmentosa aged from 7 to 73 years were enrolled in this
      study. Visual acuity and visual function tests (visual field, full-field
      electroretinogram) was performed and low-vision aids tested. Information about
      the use of the remaining vision was obtained. After choosing the best optical or
      electronic devices and before their prescription, a low-vision training program
      was carried out. RESULTS: The best corrected visual acuity varied from HM (hand
      movements) to 20/40 for distance and visual acuity better than 16M to 0.5M for
      near. 90% of the patients had optical devices prescribed: 13 for near, 9 for
      distance, 2 electronic devices and 3 filters. Three patients with extremely
      narrow visual field and very low visual acuity were referred to orientation and
      mobility. CONCLUSIONS: The low-vision aids were useful for the retinitis
      pigmentosa patients: telescopes, hand-held magnifiers, stand magnifiers, half-eye
      base-in prism lenses, electronic devices and illumination control were beneficial
      to enhance visual acuity and visual efficiency. The prescription of low-vision
      aids was helpful in daily-life activities and a high level of satisfaction with
      the implemented visual rehabilitation program was reported.

PMID- 17187137
TI  - [Transcanalicular laser-assisted dacryocystorhinostomy: initial results].
AB  - PURPOSE: To describe the technique and initial results of laser-assisted
      dacryocystorhinostomy performed through the canaliculi. METHODS: Ten patients
      with nasolacrimal duct obstruction underwent transcanalicular laser-assisted
      dacryocystorhinostomy. A silicone tube was inserted through the canaliculi and
      the ostium into the nasal cavity where it will be kept for 6 months. RESULTS: All
      ten operations were performed without negative occurrences. One patient presented
      displacement of the silicone tube one day after surgery. Nine of the ten patients
      reported disappearance of epiphora at the end of the first week following
      surgery. During the first month, one of these patients presented with epiphora
      due to obstruction of the lacrimal-nasal fistula and another lost the silicone
      tube in the first month following surgery. CONCLUSIONS: Transcanalicular laser
      assisted dacryocystorhinostomy is a potentially useful method to perform
      dacryocystorhinostomy.

PMID- 17187138
TI  - Comparison between the 1% and 2% ibopamine provocative test in primary open-angle
      glaucoma patients: sensitivity, specificity and tolerability.
AB  - PURPOSE: To compare intraocular pressure (IOP) rise in normal individuals and
      primary open-angle glaucoma patients and the safety and efficacy of ibopamine eye
      drops in different concentrations as a provocative test for glaucoma. METHODS:
      Glaucoma patients underwent (same eye) the ibopamine provocative test with two
      concentrations, 1% and 2%, in a random sequence at least 3 weeks apart, but not
      more than 3 months. The normal individuals were randomly submitted to one of the
      concentrations of ibopamine (1% and 2%). The test was considered positive if
      there was an IOP rise greater than 3 or 4 mmHg at 30 or 45 minutes to test which
      subset of the test has the best sensitivity (Se)/specificity (Sp). RESULTS: There
      was no statistically significant difference in any of the IOP measurements,
      comparing 1% with 2% ibopamine. The IOP was significantly higher at 30 and 45
      minutes with both concentrations (p < 0.001). The best sensitivity/specificity
      ratio was achieved with the cutoff point set as greater than 3 mmHg at 45 minutes
      with 2% ibopamine (area under the ROC curve: 0.864, Se: 84.6%; Sp:73.3%). All
      patients described a slight burning after ibopamine's instillation. CONCLUSION:
      2% ibopamine is recommended as a provocative test for glaucoma. Because both
      concentrations have similar ability to rise IOP, 1% ibopamine may be used to
      treat ocular hypotony.

PMID- 17187139
TI  - [Costs and efficacy of type A botulinum toxin for the treatment of essential
      blepharospasm and hemifacial spasm].
AB  - PURPOSE: To evaluate the costs and efficacy of type A botulinum toxin in the
      treatment of essential blepharospasm and hemifacial spasm. METHODS: Pacients with
      essential blepharospasm and hemifacial spasm had their files analyzed. All
      patients were treated with type A botulinum toxin (Dysport) between April 2002
      and May 2004 at the Oculoplastic Clinics of "Santa Casa de Sao Paulo". Twenty
      seven patients presented essential blepharospasm and 23 presented hemifacial
      spasm. Information about the patient's degree of satisfaction after treatment,
      complaints and personal costs were recorded by a questionnaire, and information
      about the costs of Dysport treatment were obtained at the administration
      department of "Santa Casa de Sao Paulo". Wilcoxon and Mann-Whitney tests were
      used for statistical analysis. RESULTS: 1- The annual treatment costs were R
      Dollars 1,239.32 for essential blepharospasm and R Dollars 661.72 for hemifacial
      spasm. 2- The patient's annual costs were R Dollars 145.48 for essential
      blepharospasm and R Dollars 6.07 for hemifacial spasm. 3- The hospital's annual
      costs for the treatment were R Dollars 1,095.84 for essential blepharospasm and R
      Dollars 535.65 for hemifacial spasm. 4- Dysport treatment is successful in both
      essential blepharospasm and hemifacial spasm. CONCLUSIONS: The costs of essential
      blepharospasm and hemifacial spasm treatment with Dysport are high, mainly
      because of the toxin price. On economic analysis of health, we can conclude that
      this procedure has an excellent cost-benefit ratio.

PMID- 17187140
TI  - [Artificial neural networks applied to study allergic conjunctivitis screening
      questionnaire].
AB  - PURPOSE: To evaluate sensibility and specificity of a screening questionnaire
      with multivariable analysis, compare them and elaborate an artificial neural
      network for future screenings. METHODS: Observational, transversal study
      performed at UNIFESP, with 48 patients with allergic conjunctivitis and 54
      children without the disease. Their age ranged between 3 and 14 years and there
      was no restriction related to gender, systemic allergy or treatment. The
      questionnaire was applied and multivariable statistical analysis was performed.
      Finally, an artificial neural network was elaborated. RESULTS: Mean age was 8.4
      years (7-13) and male gender was more frequent (60.7%). Mean score was 10.04 (0
      18), and it was higher in the study group (p < 0.001). Allergic diagnosis was
      increased with the inclusion of the fifth question in 68.8%. Kappa coefficient
      was low (0.337; p = 0.071) and showed no agreement between diagnosis made by the
      questionnaire and clinical examination. Only the question number five had good
      sensitivity (85.4%) and specificity (85.1%). The cutoff point to separate
      allergic patients was 10 (sensitivity = 77.08% and specificity = 79.63%). The
      artificial neural network predicted allergic diagnosis in 100% using 7 of the 15
      existent items. CONCLUSIONS: An efficient model was developed using seven
      questions, in a manner that its application might be easy to large populations.

PMID- 17187141
TI  - Lack of circadian change of concentration of C-type natriuretic peptide in rabbit
      aqueous humor.
AB  - PURPOSE: To determine whether there is a circadian change of the concentration of
      C-type natriuretic peptide (CNP) in rabbit aqueous humor. METHODS: Forty-one male
      white New Zealand rabbits were submitted to a 12 h light and 12 dark lighting
      schedule; lights on was at 0 h, lights off at 12 h. C-type natriuretic peptide
      was assayed at 3 light (2 h, 6 h and 10 h) and 3 dark (14,18 and 22 h) times. All
      groups consisted of four animals but two had more animals to increase the power
      of tests (6 h, n = 12; 22 h, n = 13). Dependence between the two eyes was tested
      by Pearson's correlation. The mean of two eyes was considered for analysis.
      Differences in concentration in pg/200 ml were evaluated by one-way ANOVA, t test
      and COSINOR analysis. RESULTS: There were no significant differences between the
      6 analyzed groups (one-way ANOVA p = 0.157). Pooled into two groups (light and
      dark), the C-type natriuretic peptide concentration of the light group was lower,
      2.626 +/- 0.92 pg/200 ml compared with the dark group 3.02 +/- 1.16 pg/200 ml but
      did not reach a significant difference (t test; p = 0.23). COSINOR analysis was
      not statistically significant (R% = 7.72 p = 0.209). CONCLUSION: These data
      demonstrate that the concentration of CNP in aqueous humor did not show a
      statistically significant circadian change in rabbits entrained to a 12 h light:
      12 h dark lighting schedule.

PMID- 17187143
TI  - Influence of blue light spectrum filter on short-wavelength and standard
      automated perimetries.
AB  - PURPOSE: To evaluate the influence of a blue light spectrum filter (BLSF),
      similar in light spectrum transmittance to the intraocular lens Acrysof Natural,
      on standard automated perimetry (SAP) and short-wavelength automated perimetry
      (SWAP). METHODS: Twenty young individuals (< 30 y.o.), without any systemic or
      ocular alterations (twenty eyes) underwent a random sequence of four Humphrey
      visual field tests: standard automated perimetry (SAP) and short-wavelength
      automated perimetry (SWAP) with and without a blue light spectrum filter. All
      patients had intraocular pressure lower than 21 mmHg, normal fundus
      biomicroscopy, and no crystalline lens opacity. Foveal threshold (FT), mean
      deviation (MD), and pattern standard deviation (PSD) indexes obtained from the
      visual field tests and the difference caused by eccentricity in short-wavelength
      automated perimetry examinations were analyzed using paired t test.
      Interindividual variability (standard deviation) was calculated using Pitman's
      test for correlated samples. RESULTS: Statistically significant reductions in the
      mean deviation (p < 0.001) and in the foveal threshold (p < 0.001) measured by
      short-wavelength automated perimetry with the use of the blue light spectrum
      filter in comparison to short-wavelength automated perimetry without the use of
      the blue light spectrum filter were observed, but not in standard automated
      perimetry exams. No other parameters showed statistically significant differences
      in the short-wavelength automated perimetry and standard automated perimetry
      tests. Interindividual standard deviation of the test points in the short
      wavelength automated perimetry exams increased with eccentricity both with and
      without the use of the blue light spectrum filter, as sensitivity for inferior
      and superior hemifields (inferior hemifield minus superior hemifield), but no
      statistically significant difference in the variability when comparing the use or
      not of the blue light spectrum filter was noted. When comparing only the four
      most inferior points and the four most superior points, the inferior-superior
      difference increases in both situations - without and with the use of the blue
      light spectrum filter. The difference between without and with the use of the
      blue light spectrum filter was not statistically significant. CONCLUSION:
      Statistically significant reductions in mean deviation and foveal threshold in
      the short-wavelength automated perimetry with the use of the blue light spectrum
      filter were observed, but not in standard automated perimetry examinations.
      Additional studies are necessary to determine the influence of intraocular lenses
      with short-wavelength light filter after cataract extraction on short-wavelength
      automated perimetry.

PMID- 17187142
TI  - Comparative study of scientific publications in Ophthalmology and Visual Sciences
      in Argentina, Brazil, Chile, Paraguay and Uruguay (1995-2004).
AB  - PURPOSE: The study aimed to measure the scientific production in Ophthalmology
      and Vision (O&V) in Argentina, Brazil, Chile, Paraguay and Uruguay over a period
      of 10 years (1995-2004), in order to find out temporal evolution and variations
      in this field of research. METHODS: PubMed / Medline was used to retrieve records
      on O&V research literature. The search strategy included keywords, country in the
      affiliation field and publication date. Data were extracted from each citation
      and recorded in a spreadsheet. Subsequent analysis focused on type and main topic
      of publication, journals where articles had been published, and evolution of
      research done on animals and humans. RESULTS: A total of 1,216 citations were
      retrieved. Brazil had the largest number of authored publications with an average
      annual production of 82.4, followed by Argentina with 31.0, Chile 6.4, Uruguay
      1.6, and Paraguay 0.2. The ratio of articles on O&V relative to publications
      involving Health Science ranged from 1.0 to 2.3. The frequency of publications
      almost tripled from 1995 to 2004. Research on humans showed a significant
      increase in Argentina and Brazil. CONCLUSIONS: Results provide initial benchmarks
      on O&V publication rates in countries in South America that may be useful to
      follow research trends.

PMID- 17187144
TI  - Quality of health care: patient satisfaction in a university hospital.
AB  - OBJECTIVE: To evaluate patient characteristics and satisfaction in an outpatient
      service at a university hospital, aiming at obtaining subsidies for
      standardization of a quality assessment program. METHOD: Patient-representative
      sample was selected. It consisted of users of the Ophthalmology Outpatient
      Service at the Hospital das Clinicas, Universidade Estadual de Campinas
      (UNICAMP). A structured questionnaire was applied through interview, including
      the following variables: personal characteristics (gender, age, literacy, job),
      type of appointment (new patient, follow-up), waiting time for the first
      appointment, opinion regarding ease of access to the hospital, assistance at the
      front desk, time spent in the waiting room on the appointed day, quality of care,
      degree of satisfaction with the consultation and general evaluation of the
      assistance. RESULTS: The sample was characterized by patients with low literacy
      and socioeconomic level; 21.7% had a steady income. The majority of them think
      that it is easy to obtain an appointment. According to patients, the mean waiting
      time for the appointment was 94.6 minutes and 45.3% of them received no
      orientation after the appointment. Final evaluation of the quality of assistance
      was positive and patients were satisfied with the provided assistance.
      CONCLUSION: Although a high level of satisfaction regarding the provided service
      was observed, when the various factors that can affect patient satisfaction are
      considered, users reported limitations as concerns quality. Evaluation allowed a
      better knowledge about the provided service in a university hospital and pointed
      to the possibility of implantation of quality assessment routines.

PMID- 17187145
TI  - [Ophthalmoplegic migraine: case report].
AB  - Ophthalmoplegic migraine is a rare syndrome in which episodic fixed unilateral
      headaches are associated with ipsilateral ophthalmoplegia. Its physiopathology
      remains obscure. We describe a case in a patient with ophthalmoplegic migraine
      diagnosed according to the International Headache Society (IH-2004) criteria, who
      showed an unusual clinical presentation. The first ophthalmoplegic migraine
      episode occurred in adult life. Pain side changed in one episode. Oculomotor
      abnormalities were painless during the last crisis. Since diagnosis is made by
      exclusion, differential diagnosis and need for etiologic investigation are
      discussed.

PMID- 17187146
TI  - A case of anterior internal ophthalmomyiasis: case report.
AB  - A case of anterior internal ophthalmomyiasis is described. A 27-year-old female
      from Northern Brazil presenting with anterior uveitis and vitritis had a fly
      larva surgically removed from the anterior chamber of the left eye. The species
      was Cochliomyia hominivorax. The larva was covered by macrophages and foreign
      body giant cells characterizing a foreign body granulomatous reaction.

PMID- 17187147
TI  - Different presentations of intraretinal fluid collections in optic disc pits: OCT
      study of 3 cases.
AB  - The congenital optic disc pit is a rare anomaly that can lead to major visual
      impairment associated with subretinal fluid accumulation. The authors describe
      the optical coherence tomography study of three cases of untreated congenital
      optic disc pits with different levels of visual impairment and its different
      presentations of intraretinal fluid collections.

PMID- 17187148
TI  - Intralenticular metal foreign body: case report.
AB  - Intralenticular foreign bodies comprise about 5% to 10% of all intraocular
      foreign bodies and can result in serious complications. The management depends on
      some factors like size, location, material type and the risk of infection. We
      present a patient with an intralenticular metal foreign body in the left eye
      that, following initial treatment with topical steroid and antibiotic, underwent
      lens aspiration with removal of the intralenticular foreign body and insertion of
      a posterior chamber intraocular lens with good visual outcome.

PMID- 17187149
TI  - Clinical features, histopathological analysis and surgical treatment of a free
      floating vitreous cyst: a case report.
AB  - The authors present a report of a 44-year-old female patient, with complaints of
      visual disturbances in the left eye. The symptoms were present for at least 5
      years and worsened in the last 2 years, impairing her activities. The patient
      reported perception of a floating circle, which blurred her vision. There was no
      previous history of trauma, infectious or inflammatory disease. Clinical
      evaluation included physical examination, laboratory testing, abdominal
      ultrasonography, thorax X-ray and head tomography. Ophthalmologic examination
      consisted of visual acuity, motility tests, biomicroscopy, tonometry and indirect
      ophthalmoscopy. Complementary investigation was done with a and b scan ocular
      ultrasonography. The chosen therapeutic approach to excise the cyst was pars
      plana vitrectomy, successfully performed. Anatomopathologic analysis revealed a
      pigmented vitreous cyst, of possible congenital origin, described as a cystic
      choristoma from the primitive hyaloid system. Benign evolution, clinical findings
      and histopathological analysis corroborated the diagnostic hypothesis of a cystic
      choristoma of the primitive hyaloid system. Surgery (pars plana vitrectomy) was
      successful and the patient returned with visual acuity of 20/20 in both eyes, and
      with no further complaints.

PMID- 17187150
TI  - [Treatment of neovascular age-related macular degeneration with antiangiogenic
      drugs].
AB  - Age-related macular degeneration (ARMD) remains a leading cause of blindness in
      the western world. Several clinical forms of the disease are recognized, whereas
      choroidal neovascularization (CNV) represents an important manifestation suitable
      for treatment. The treatment of CNV has been a major focus of research in the
      past decades, and the first evidence-based established therapy was laser
      photocoagulation, which reduces the risk of visual loss in extrafoveal lesions.
      In the late 90's photodynamic therapy has been established as an efficient method
      for the treatment of predominantly classic and occult CNV. Additional therapies
      such as macular translocation, submacular surgery, and indocyanine-mediated
      prothrombosis are currently under investigation in large-scale clinical trials.
      Molecular biology has recently provided a better comprehension of the
      pathogenesis of ARMD, and vascular endothelial growth factor (VEGF) was
      recognized as key mediator in the angiogenesis of CNV-formation. Therefore, the
      pharmacological approach rose as a key research area to treat CNV. The first FDA
      approved agent for CNV-therapy is aptamer pegaptanib sodium (Macugen), which
      inactivates the key angiogenic isoform VEGF165. Additional VEGF-blockers such as
      ranibizumab RhuFab V2 (Lucentis) and bevacizumab (Avastin) are under evaluation
      in major clinical studies. Impressive results of intravitreal bevacizumab were
      released recently. Moreover, the steroid-derived anecortave acetate as well as
      the corticosteroid triamcinolone acetate have been proposed as methods for
      treatment of wet-ARMD. This paper presents the rationale and principles of the
      pharmacologic antiangiogenic therapy for CNV in ARMD.

PMID- 17187151
TI  - [Chromatic sense: types of defects and clinical evaluation tests].
AB  - Evaluation of the chromatic sense has a great value in ophthalmic practice, both
      for diagnosis of the congenital defects (daltonism), as well as for diagnosis and
      follow-up of acquired defects. Many clinical tests are available to be used for
      this purpose. However it is necessary to know the details and sensitivity of each
      test, since there are many variations in the results, depending on the searched
      condition, if congenital or acquired pathologies. Our goal is to review the types
      of defects of the chromatic sense and provide information about the main current
      available tests and their best purpose. We further emphasize the importance of
      standard illumination procedure in the application of the tests.

PMID- 17187152
TI  - [Routines for refractory surgeries screening in cornea donors].

PMID- 17187155
TI  - Hypospadias: an update.
AB  - Hypospadias is the most common congenital anomaly of the penis. The problem
      usually develops sporadically and without an obvious underlying cause. The
      ectopically positioned urethral meatus lies proximal to the normal site and on
      the ventral aspect of the penis, and in severe cases opens onto the scrotum or
      perineum. The foreskin on the ventral surface is deficient, while that on the
      dorsal surface is abundant, giving the appearance of a dorsal hood. Chordee is
      more common in severe cases. Cryptorchidism and inguinal hernia are the most
      common associated anomalies. The frequency of associated anomalies increases with
      the severity of hypospadias. For isolated anterior or middle hypospadias,
      laboratory studies are not usually necessary. Screening for urinary tract
      anomalies should be considered in patients with posterior hypospadias and in
      those with an anomaly of at least one additional organ system. The ideal age for
      surgical repair in a healthy child is between 6 and 12 months of age. Most cases
      can be repaired in a single operation and on an outpatient basis. Even patients
      with a less than perfect surgical result are usually able to enjoy a satisfactory
      sexual life.

PMID- 17187154
TI  - Evaluation and diagnostic testing of erectile dysfunction in the era of
      phosphodiesterase type 5 inhibitors.
AB  - The diagnosis and treatment of erectile dysfunction has changed dramatically
      since the availability of safe and effective oral therapies. Unfortunately, not
      all men can be adequately treated in this way, and might require more invasive
      testing to diagnose and treat the specific cause of their dysfunction. This
      review looks at the tests and strategies available for men who cannot be treated
      by oral therapy alone.

PMID- 17187156
TI  - Inhibition of mouse acrosome reaction and sperm-zona pellucida binding by anti
      human sperm membrane protein 1 antibody.
AB  - AIM: To investigate the possible functions of human sperm membrane protein (hSMP
      1) in the process of fertilization. METHODS: A 576-bp cDNA fragment of HSD-1 gene
      coding for the extracellular domain of hSMP-1 was cloned and expressed. The
      localization of this protein on human and mouse sperm was determined by indirect
      immunofluorescent staining by using anti-recombinant hSMP-1 (anti-rhSMP-1)
      antibodies. Sperm acrosome reaction and sperm-zona pellucida (ZP) binding assay
      were carried out in 10-week-old BALB/c mice. RESULTS: Recombinant hSMP-1 was
      successfully cloned and expressed. The expression of the native protein was
      limited on the acrosome of human and mouse sperm. Treatment of anti-rhSMP-1
      antibodies significantly decreased the average number of sperms bound to each
      egg. Meanwhile, the percentage of acrosome reaction was decreased in comparison
      to pre-immune control after treatment with anti-rhSMP-1 (P < 0.05). CONCLUSION:
      The results suggest that anti-rhSMP-1 antibody inhibited mouse acrosome reaction
      and sperm-ZP binding.

PMID- 17187157
TI  - Alpha-vitamin E derivative, RRR-alpha-tocopheryloxybutyric acid inhibits the
      proliferation of prostate cancer cells.
AB  - AIM: To investigate the activity of RRR-alpha-tocopheryloxybutyric acid (TOB), an
      ether analog of RRR-alpha-tocopheryl succinate (VES), in prostate cancer cells.
      METHODS: VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rv1
      cells and primary-cultured prostate fibroblasts. The proliferation rates were
      determined by MTT assay, the cell viabilities were determined by trypan blue
      exclusion assay, and the cell deaths were evaluated by using Cell Death Detection
      ELISA kit. The protein expression levels were determined by Western blot
      analysis. RESULTS: The MTT growth assay demonstrated that TOB could effectively
      suppress the proliferation of prostate cancer cells, but not normal prostate
      fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and
      induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB
      and VES suppressed prostate-specific antigen (PSA) at the transcriptional level
      leading to reduced PSA protein expression. Furthermore, vitamin D receptor (VDR)
      expression increased after the addition of TOB. CONCLUSION: Our data suggests
      that the VES derivative, TOB, is effective in inhibiting prostate cancer cell
      proliferation, suggesting that TOB could be used for both chemopreventive and
      chemotherapeutic purposes in the future.

PMID- 17187158
TI  - Assessment of seminal plasma laminin in fertile and infertile men.
AB  - AIM: To assess laminin levels in the seminal plasma of infertile and fertile men,
      and to analyze the correlation of laminin levels with sperm count, age, sperm
      motility and semen volume. METHODS: One hundred and twenty-five recruited men
      were equally divided into five groups according to their sperm concentration and
      clinical examination: fertile normozoospermia, oligoasthenozoospermia, non
      obstructive azoospermia (NOA), obstructive azoospermia (OA) and congenital
      bilateral absent vas deferens (CBAVD). The patients' medical history was
      investigated and patients underwent clinical examination, conventional semen
      analysis and estimation of seminal plasma laminin by radioimmunoassay. RESULTS:
      Seminal plasma laminin levels of successive groups were: 2.82 +/- 0.62, 2.49 +/-
      0.44, 1.77 +/- 0.56, 1.72 +/- 0.76, 1.35 +/- 0.63 U/mL, respectively. The fertile
      normozoospermic group showed the highest concentration compared to all infertile
      groups with significant differences compared to azoospermic groups (P<0.05).
      Testicular contribution was estimated to be approximately one-third of the
      seminal laminin. Seminal plasma laminin demonstrated significant correlation with
      sperm concentration (r = 0.460, P < 0.001) and nonsignificant correlation with
      age (r = 0.021, P = 0.940), sperm motility percentage (r = 0.142, P = 0.615) and
      semen volume (r = 0.035, P = 0.087). CONCLUSION: Seminal plasma laminin is
      derived mostly from prostatic and testicular portions and minimally from the
      seminal vesicle and vas deferens. Estimating seminal laminin alone is not
      conclusive in diagnosing different cases of male infertility.

PMID- 17187159
TI  - Frequency of Y chromosome microdeletions and chromosomal abnormalities in
      infertile Thai men with oligozoospermia and azoospermia.
AB  - AIM: To investigate the possible causes of oligozoospermia and azoospermia in
      infertile Thai men, and to find the frequencies of Y chromosome microdeletions
      and cytogenetic abnormalities in this group. METHODS: From June 2003 to November
      2005, 50 azoospermic and 80 oligozoospermic men were enrolled in the study. A
      detailed history was taken for each man, followed by general and genital
      examinations. Y chromosome microdeletions were detected by multiplex polymerase
      chain reaction (PCR) using 11 gene-specific primers that covered all three
      regions of the azoospermic factor (AZFa, AZFb and AZFc). Fifty men with normal
      semen analysis were also studied. Karyotyping was done with the standard G- and Q
      banding. Serum concentrations of follicle stimulating hormone (FSH), luteinizing
      hormone (LH), prolactin (PRL) and testosterone were measured by
      electrochemiluminescence immunoassays (ECLIA). RESULTS: Azoospermia and
      oligozoospermia could be explained by previous orchitis in 22.3%, former
      bilateral cryptorchidism in 19.2%, abnormal karyotypes in 4.6% and Y chromosome
      microdeletions in 3.8% of the subjects. The most frequent deletions were in the
      AZFc region (50%), followed by AZFb (33%) and AZFbc (17%). No significant
      difference was detected in hormonal profiles of infertile men, with or without
      microdeletions. CONCLUSION: The frequencies of Y chromosome microdeletions and
      cytogenetic abnormalities in oligozoospermic and azoospermic Thai men are
      comparable with similarly infertile men from other Asian and Western countries.

PMID- 17187160
TI  - Seasonal variation in semen quality of swamp buffalo bulls (Bubalus bubalis) in
      Thailand.
AB  - AIM: To test the hypothesis that season affects the semen quality of swamp
      buffalo (Bubalus bubalis) bulls used for artificial insemination (AI) under
      tropical conditions in Thailand, as it does in Bos taurus and Bos indicus.
      METHODS: Clinical and andrological examinations, and monitoring of semen
      production and quality were carried out on five mature, healthy swamp buffalo AI
      bulls in Thailand from July 2004 to the end of June 2005. Sperm output, motility,
      morphology and plasma membrane integrity (PMI) were compared between three
      seasons of the year (rainy, i.e. July-October; winter, i.e. November-February;
      and summer, i.e. March-June) with distinct ambient temperature and humidity.
      RESULTS: All bulls were diagnosed as clinically healthy and with good libido
      throughout the study. Ejaculate volume, pH, sperm concentration, total sperm
      number and initial sperm motility did not differ between seasons, whereas PMI and
      the relative proportion of morphologically normal spermatozoa were highest in
      summer and lowest in winter (P<0.05). Buffalo age, week of collection and season
      influenced sperm morphology (P < 0.05-0.001). Among morphological abnormalities,
      only proportions of tail defects were affected by season, being highest in the
      rainy season and lowest in summer (P<0.001). In conclusion, climatic changes did
      not seem to largely affect semen sperm output or viability. Although the
      proportions of PMI and tail abnormalities were affected by season, they were
      always below what is considered unacceptable for AI bull sires. CONCLUSION:
      Seasonal changes did not appear to cause deleterious changes in sperm quality in
      swamp buffalo AI-sires in tropical Thailand.

PMID- 17187161
TI  - Sperm lipid peroxidation and pro-inflammatory cytokines.
AB  - AIM: To investigate if interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10
      (IL-10), interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha)
      are able to stimulate the level of lipid peroxidation of sperm membranes, either
      alone or in the presence of leukocytes. METHODS: Semen samples from
      normozoospermic donors were prepared by density gradient. The sperms were exposed
      to the indicated cytokines, at physiological and infection-inflammation
      concentrations, in the absence or presence of leukocytes. Lipid peroxidation of
      the sperm membranes was determined by measuring malondialdehyde (MDA) and 4
      hydroxialkenals (HAE) formation. RESULTS: TNF-alpha, IL-8 and IFN-gamma increased
      the level of sperm membrane lipid peroxidation when tested at physiological
      concentrations. At infection-inflammation concentrations, only IL-8 was able to
      produce a higher effect. When assayed in the presence of leucocytes, IL-8 and TNF
      alpha showed a higher effect at infection-inflammation concentrations than at
      physiological concentrations. Finally, IL-8 showed a higher effect in the
      presence of leukocytes than in their absence at both physiological and infection
      inflammation concentrations. TNF-alpha also showed a higher effect when assayed
      in the presence of leukocytes than in their absence, but only at infection
      inflammation concentrations. There was no effect of IL-6 or IL-10 in any of the
      tested conditions. CONCLUSION: Several pro-inflammatory cytokines at
      physiological concentrations increase the level of lipid peroxidation of sperm
      membranes, which could be important for the sperm fecundation process. However,
      infection-inflammation concentrations of some cytokines, such as IL-8 and TNF
      alpha, either alone or in the presence of leukocytes, could drive the lipid
      peroxidation of the spermatozoa plasma membrane to levels that can affect the
      sperm fertility capacity.

PMID- 17187162
TI  - Increased oxidative damage of sperm and seminal plasma in men with idiopathic
      infertility is higher in patients with glutathione S-transferase Mu-1 null
      genotype.
AB  - AIM: To examine whether a relationship exists between glutathione S-transferase
      Mu-1 (GSTM1) gene polymorphism and the susceptibility of sperm and seminal plasma
      from patients with idiopathic infertility to oxidative stress. METHODS: Fifty-two
      men with idiopathic infertility and 60 healthy fertile men were recruited to this
      study. GSTM1 gene polymorphism was determined by polymerase chain reaction (PCR)
      and both the infertile and control individuals were divided into GSTM1 null and
      GSTM1 positive groups according to their GSTM1 gene structure. We compared
      reactive oxygen species (ROS) generation, malondialdehyde (MDA), protein
      carbonyls and glutathione (GSH) concentrations, and glutathione S-transferase
      (GST) activity in seminal plasma and spermatozoa from infertile patients and
      controls with respect to GSTM1 genotype. RESULTS: Significantly higher levels of
      oxidative stress and damage markers were found in idiopathic infertile men with
      the GSTM1 null genotype compared with those with the GSTM1 positive genotype.
      There was no significant difference in genotype distribution for the GSTM1
      variant between the idiopathic infertile subjects and fertile subjects. Patients
      with the GSTM1 null genotype also had lower sperm concentrations than those with
      GSTM1 positive genotype. CONCLUSION: Our results suggest that the susceptibility
      of sperm and seminal plasma to oxidative stress is significantly greater in
      idiopathic infertile men with the GSTM1 null genotype compared with those
      possessing the gene. Therefore, in patients with idiopathic infertility, GSTM1
      polymorphism might be an important source of variation in susceptibility of
      spermatozoa to oxidative damage.

PMID- 17187163
TI  - Protective effects of vitamin E on ethane dimethane sulfonate-induced testicular
      toxicity in rats.
AB  - AIM: To evaluate the protective/ameliorative effects of vitamin E (vit E) on
      ethane dimethane sulfonate (EDS)-induced testicular toxicity in rats. METHODS:
      The rats were assigned to eight groups, seven rats in each, and were injected
      intraperitoneally with vehicle, a single dose of ethane dimethane sulfonate (EDS)
      (75 mg/kg bodyweight), vit E (100 mg/kg bodyweight) or EDS + vit E for 3? days.
      Thereafter, the rats were weighed, anaesthetized with ether and killed by
      cervical dislocation. The left testis weights were recorded and the relative
      testis weights were calculated. The left testes were processed for routine
      paraffin embedding. Three right testes from each group were taken randomly and
      then processed for routine electron microscopy. Tissue sections were examined
      using light and electron microscopy, and were scored for histopathological
      changes. RESULTS: Vit E coadministration did not prevent the bodyweight loss on
      days 3 and 7. However, vit E administration prevented the EDS-induced testicular
      weight loss in rats that received vit E for 3 days but not 7 days. The relative
      testis weight was higher on day 3 (instead of on day 7) than other groups.
      Nevertheless, the testis histology was not markedly protected by vit E in the EDS
      treated rats. Detailed microscopic assessment showed few Leydig cells and
      abundant fibroblast-like cells indicating only some protection. CONCLUSION: Vit E
      cotreatment showed partial protective effects on the testicular weight and
      testicular histology in rats that received EDS.

PMID- 17187164
TI  - Different hemodynamic responses by color Doppler ultrasonography studies between
      sildenafil non-responders and responders.
AB  - AIM: To determine if there are different penile hemodynamic patterns between
      sildenafil non-responders and responders by using color Doppler ultrasonography.
      METHODS: A total of 69 erectile dysfunction (ED) patients aged 22-79 years were
      enrolled into the present study. Thirty-eight (55.1%) men with ED who did not
      respond to four attempts of treatment with 100 mg sildenafil after re-education
      were classified as sildenafil non-responders. A combination of three vasodilator
      drugs, 1.25 mg papaverine, 0.4 mg phentolamine and 5 mg prostaglandin E1, was
      given by intracavernous injection before penile Doppler ultrasonography was
      carried out. The erectile response to intracavernous injection and vascular
      parameters including peak systolic velocity (PSV), resistance index (RI), end
      diastolic velocity (EDV) and cavernosa artery diameter (CD) were measured and the
      results between sildenafil non-responders and responders were compared. RESULTS:
      No statistical difference in vascular parameters measured by Doppler
      ultrasonography studies between non-responders and responders was noted.
      Sildenafil non-responders had a poorer penile rigidity response to intracavernous
      injection than responders (P < 0.05). Among patients with adequate PSV (>or=30
      cm/s) and abnormal EDV (> 5 cm/s), individuals in the non-responder group had
      fewer positive responses to intracavernous vasodilator injection than in the
      responder group (35.3% vs. 72.2%, P < 0.05). Advanced age and comorbidity with
      diabetes mellitus were significantly associated with sildenafil non-response (P <
      0.05). CONCLUSION: Sildenafil non-responders were characterized by a poorer
      penile rigidity response to intracavernous injection and had an associated
      impaired veno-occlusive mechanism. Advanced age and comorbidity with diabetes
      mellitus were two common factors associated with non-response.

PMID- 17187165
TI  - Improved spontaneous erectile function in men with mild-to-moderate arteriogenic
      erectile dysfunction treated with a nightly dose of sildenafil for one year: a
      randomized trial.
AB  - AIM: To test the hypothesis that sildenafil (50 mg nightly for one year) can
      improve spontaneous erectile function (EF) in men with mild-to-moderate
      arteriogenic erectile dysfunction (ED) responsive to erectogenic treatment.
      METHODS: In a prospective open-label trial, 112 men with ED were randomized to
      sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months,
      followed by one-month and 6-month non-medicated periods. Non-randomized, non
      medicated men with ED were also assessed. The EF domain of the International
      Index of Erectile Function (IIEF EF) and the peak systolic velocity (PSV) of
      penile cavernous arteries were used to measure the efficacy. RESULTS: After
      sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in
      29 of 48 (60.4%, 95% confidence interval [CI]: 45.3-74.2%) of the nightly group
      vs. 4 of 49 (8.2%, 95% CI: 2.3-19.6%) of the as-needed group. PSV improved by
      11.2 cm/s (95% CI: 4.7-21.4; P=0.012) in the nightly group but only by 3.4 cm/s (
      5.1-14.7; P=0.435) in the as-needed group. IIEF EF normalized in 1 of 18 (5.6%,
      95% CI: 0.1-27.3%) non-medicated men and the PSV declined slightly. Six months
      after treatment, the IIEF EF remained normal and PSV was stabilized in most
      (28/29, 97%) nightly group men who had initially normalized. CONCLUSION:
      Sildenafil nightly for one year resulted in ED regression that persisted well
      beyond the end of treatment, so that spontaneous EF was characterized as normal
      on the IIEF in most men. The results from this open-label, randomized trial
      warrant verification under double-blind, placebo-controlled conditions.

PMID- 17187166
TI  - Prevalence of anxiety and depression during pregnancy in a private setting
      sample.
AB  - OBJECTIVES: To estimate the prevalence and risk factors for antenatal anxiety
      (AA) and antenatal depression (AD). METHODS: We performed a cross sectional study
      of 432 women attending a private clinic in the city of Osasco, Sao Paulo, from
      5/27/1998 to 5/13/2002. The following instruments were used: Spielberger state
      trait anxiety inventory (STAI), Beck depression inventory (BDI), and a
      questionnaire for socio-demographic and obstetric data. Inclusion criteria were:
      pregnant women with no past or present history of depression, psychiatric
      treatment, alcohol or drug abuse and no clinical and obstetric complications. The
      prevalence of AA, according to STAI, and AD, according to Beck Inventory, were
      estimated with 95% confidence intervals (95% CI). Odds ratios and 95% CI were
      used to examine the association between AA and AD and exposures variables.
      RESULTS: The prevalence of AA, state and trait were 59.5 (95 CI%: 54.8:64.1%) and
      45.3% (95% CI: 40.6:50.0), respectively. The prevalence of AD was 19.6 (95%
      CI:15.9:23.4). In the multivariate analysis, AA-trait (OR: 5.26; 95% CI
      2.17:12.5, p < 0.001), AA-state (OR: 2.27; 95% CI 1.08:4.76, p = 0.02) and AD
      (OR: 2.43; 95% CI 1.40:4.34, p = 0.002) were associated with lower women's
      educational level. AA-trait (OR: 3.43; 95% CI 1.68:7.00, p = 0.001), AA-state
      (OR: 2.22; CI 95% 1.09:4.53, p = 0.02) and AD (OR: 2.82; CI 95% 1.35:5.97, p =
      0.005) were also associated with not being married. AA-trait was associated with
      lower women's income (OR: 2.22; 95% CI 0.98:5.26, p = 0.05) and not being white
      (OR: 1.7; 95% CI 1.00:2.91, p = 0.04), while AD was associated with lower
      couple's income (OR: 2.43; 95% CI 1.40:4.34, p = 0.001) and greater number of
      previous abortions (OR: 2.21; 95% CI 1.23:3.97, p = 0.009). CONCLUSIONS:
      Prevalence of AA and AD were high in this sample of women attending a private
      care setting, particularly AA state and trace. AA and AD were associated with
      similar socio-demographic and socio-economic risk factors, suggesting some common
      environmental stressors may be involved.

PMID- 17187167
TI  - Bile duct cyst as precursor to biliary tract cancer.
AB  - BACKGROUND: Bile duct cysts (BDC) are rare, of uncertain origin, and occur most
      often in young females of Asian descent. Increasingly, BDCs are reported in the
      Western population, often with coexistent biliary tract cancer. METHODS: The
      PubMed and Medline literature databases were searched for pertinent publications
      regarding the clinical association and molecular biological development of
      cancerogenesis in BDC. Reports from the last two decades were emphasized.
      RESULTS: Cancer is found in 10-30% of adults with BDC. The cancer-risk is low in
      childhood (<1% in the first decade), and shows a clear increase with age.
      Cholangiocarcinoma is the most common malignancy in BDC, and represents a 20- to
      30-fold risk compared to the general population. The mean age of malignancy in
      BDC is 32 years (about two decades earlier than in the general population). Type
      I and type IV cysts show a higher cancer incidence, even after cyst excision.
      Pathological findings strongly suggest a hyperplasia-dysplasia-carcinoma sequence
      in carcinogenesis of pancreatico-biliary maljunction (PBM). Reflux of pancreatic
      enzymes, amylase, bile stasis, and an increased intraductal concentration of bile
      acids contribute to proliferative activity of bile acids in BDC. While
      microsatellite instability, k-ras mutations, expression of COX-2 and bcl-2, and
      increased telomerase activity seem to occur early; involvement of cyclin D1, beta
      catenin, DPC-4/Smad4 and p53 appear later in carcinogenesis. CONCLUSION:
      Increased molecular knowledge substantiates the clinically related cancer-risk in
      BDC. Surgery remains the golden standard for treatment, relieves patients from
      associated complications, and interrupts the cancerous potential in BDC.

PMID- 17187168
TI  - Expression of tumor antigens and heat-shock protein 70 in breast cancer cells
      after high-intensity focused ultrasound ablation.
AB  - BACKGROUND: Previous results have shown that high-intensity focused ultrasound
      (HIFU) ablation can potentially activate a host antitumor immunity. The goal of
      this study was to investigate whether the tumor antigens expressed on breast
      cancer cells may be preserved after HIFU treatment, and to explore the potential
      mechanisms regarding the enhanced antitumor response. METHODS: The primary lesion
      in 23 patients with biopsy-proven breast cancer were treated with HIFU, then
      submitted to modified radical mastectomy. By using biotin-streptavidin-peroxidase
      immunohistochemical technology, a variety of cellular molecules expressed on
      breast cancer cells, including tumor antigens and heat-shock protein 70 (HSP-70),
      were stained in all breast specimens. A complete absence of staining was recorded
      as negative, and immunoreaction of the tumor cells was considered to be positive
      for antigen expression. RESULTS: Nuclear positivity of breast cancer cells for
      proliferating cell nuclear antigen, estrogen receptor, and progesterone receptor
      was detected in 0%, 9%, and 9% of the treated samples, respectively. The positive
      rate of cytoplasmic staining for matrix metalloproteinase 9, carbohydrate antigen
      15-3, vascular endothelial growth factor, transforming growth factors beta1 and
      beta2, interleukin 6, and interleukin 10 was 0%, 52%, 30%, 57%, 70%, 48%, and 61%
      in the treated cancer cells, respectively. The positive rate of cellular membrane
      staining for epithelial membrane antigen, CD44v6, and HSP-70 was 100%, 0%, and
      100% in the zones of treated cancer cells, respectively. CONCLUSIONS: After HIFU
      ablation, some tumor antigens remained in the tumor debris. This could provide a
      potential antigen source to stimulate antitumor immune response.

PMID- 17187169
TI  - Physical illness and lifestyle risk factors in people with their first
      presentation of psychosis.
AB  - BACKGROUND: There is an increased prevalence of physical illness and poor
      lifestyle in patients with chronic schizophrenia. It is unclear whether these are
      present at the onset of psychosis or develop over the course of illness. We aimed
      to establish whether patients experiencing their first episode of psychosis have
      worse physical health and lifestyle than community controls without psychosis.
      METHOD: Eighty-nine patients with new onset illness were compared to age and sex
      matched controls for self-reported physical illness and cardiovascular and
      respiratory risk factors. RESULTS: Patients reported more physical health
      complaints, mainly respiratory, compared with age and gender matched controls
      (odds ratio 2.85, 95% confidence interval 1.2-6.7). Patients were more likely to
      be cigarette smokers (1.82, 95% CI 1.0-3.3) and eat a fast food diet (1.04, 95%
      CI 1.0-1.1), but these differences were accounted for by patients' unemployment
      status. CONCLUSIONS: Some risk factors for physical health problems are present
      at the onset of psychosis, but these may be explained by unemployment.

PMID- 17187170
TI  - Selenium protects the immature rat heart against ischemia/reperfusion injury.
AB  - The aim of the study was to find out whether administration of selenium (Se) will
      protect the immature heart against ischemia/reperfusion.The control pregnant rats
      were fed laboratory diet (0.237 mg Se/kg diet); experimental rats received 2 ppm
      Na(2)SeO(3) in the drinking water from the first day of pregnancy until day 10
      post partum. The concentration of Se in the serum and heart tissue was determined
      by activation analysis, the serum concentration of NO by chemiluminescence,
      cardiac concentration of lipofuscin-like pigment by fluorescence analysis. The 10
      day-old hearts were perfused (Langendorff); recovery of developed force (DF) was
      measured after 40 min of global ischemia. In acute experiments, 10 day-old hearts
      were perfused with selenium (75 nmol/l) before or after global ischemia.
      Sensitivity to isoproterenol (ISO, pD(50)) was assessed as a response of DF to
      increasing cumulative dose.Se supplementation elevated serum concentration of Se
      by 16%. Se increased ischemic tolerance (recovery of DF, 32.28 +/- 2.37 vs. 41.82
      +/- 2.91%, P < 0.05). Similar results were obtained after acute administration of
      Se during post-ischemic reperfusion (32.28 +/- 2.37 vs. 49.73 +/- 4.40%, P <
      0.01). The pre-ischemic treatment, however, attenuated the recovery (23.08 +/-
      3.04 vs. 32.28 +/- 2.37%, P < 0.05). Moreover, Se supplementation increased the
      sensitivity to the inotropic effect of ISO, decreased cardiac concentration of
      lipofuscin-like pigment and serum concentration of NO. Our results suggest that
      Se protects the immature heart against ischemia/reperfusion injury. It seems
      therefore, that ROS may affect the function of the neonatal heart, similarly as
      in adults.

PMID- 17187171
TI  - Analysis on the promoter region of human decidual prolactin gene in the
      progesterone-induced decidualization and cAMP-induced decidualization of human
      endometrial stromal cells.
AB  - PURPOSE: To elucidate the promoter region of human decidual prolactin (dPRL) gene
      in the human endometrial stromal cells (ESC). METHODS: Various segments of the
      human dPRL promoter that direct the expression of the secreted alkaline
      phosphatase (SEAP) reporter gene were transfected into human ESC decidualized by
      estrogen (E) + progesterone (P) or cyclic AMP (cAMP) to identify E + P or cAMP
      responsive elements. RESULTS: The region between nucleotides -2038 and -1605
      relative to the transcriptional initiation site includes two activator protein-1
      (AP-1) sites, which both provided maximal response to E + P or cAMP in
      decidualized cells. When either AP-1 site was mutated, response in the promoter
      activity to both E + P or cAMP response showed a decrease compared with control.
      The region between -310 and -285 that contains consensus-binding sequences for
      transcription factors of CCAAT/Enhancer-binding proteins (C/EBP) contributed to E
      + P and cAMP response in decidualized cells. Also, the 5'-flanking region that
      extends 79 base pairs upstream, including an imperfect cAMP response element
      (CRE), contributed to E + P and cAMP response. In cells treated with E + P or
      cAMP for 10 days, mutant of C/EBP-binding site showed an increase in promoter
      activity comparing to dPRL-2038. In contrast, treatment with PKI showed a
      decrease in promoter activity in cells treated with E + P or cAMP alone.
      CONCLUSIONS: These results suggest that cAMP-induced region of the human dPRL
      promoter resides between -1862 and -1856, -1703 and -1697, -310 and -285, and
      that the sequences between -1862 and -1856, -1703 and -1697 of the promoter
      display E + P-induced promoter activity. Furthermore, the current study indicates
      that E + P or cAMP cooperatively regulate the dPRL gene transcription through
      some transcriptional factors such as C/EBP, CREB, and other cofactor(s), and that
      some repressor(s) or corepressor(s) may be involved in the C/EBP-binding site of
      the human dPRL promoter.

PMID- 17187172
TI  - Endocannabinoids in adipocytes during differentiation and their role in glucose
      uptake.
AB  - The molecular basis for the control of energy balance by the endocannabinoid
      anandamide (AEA) is still unclear. Here, we show that murine 3T3-L1 fibroblasts
      have the machinery to bind, synthesize and degrade AEA, and that their
      differentiation into adipocytes increases by approximately twofold the binding
      efficiency of cannabinoid receptors (CBR), and by approximately twofold and
      approximately threefold, respectively, the catalytic efficiency of the AEA
      transporter and AEA hydrolase. In contrast, the activity of the AEA synthetase
      and the binding efficiency of vanilloid receptor were not affected by the
      differentiation process. In addition, we demonstrate that AEA increases by
      approximately twofold insulin-stimulated glucose uptake in differentiated
      adipocytes, according to a CB1R-dependent mechanism that involves nitric oxide
      synthase, but not lipoxygenase or cyclooxygenase. We also show that AEA binding
      to peroxisome proliferator-activated receptor-gamma, known to induce
      differentiation of 3T3-L1 fibroblasts into adipocytes, is not involved in the
      stimulation of glucose uptake.

PMID- 17187173
TI  - Cellular uptake of amelogenin, and its localization to CD63, and Lamp1-positive
      vesicles.
AB  - Proteins of the developing enamel matrix include amelogenin, ameloblastin and
      enamelin. Of these three proteins amelogenin predominates. Protein-protein
      interactions are likely to occur at the ameloblast Tomes' processes between
      membrane-bound proteins and secreted enamel matrix proteins. Such protein-protein
      interactions could be associated with cell signaling or endocytosis. CD63 and
      Lamp1 are ubiquitously expressed, are lysosomal integral membrane proteins, and
      localize to the plasma membrane. CD63 and Lamp1 interact with amelogenin in
      vitro. In this study our objective was to study the molecular events of
      intercellular trafficking of an exogenous source of amelogenin, and related this
      movement to the spatiotemporal expression of CD63 and Lamp1 using various cell
      lineages. Exogenously added amelogenin moves rapidly into the cell into
      established Lamp1-positive vesicles that subsequently localize to the perinuclear
      region. These data indicate a possible mechanism by which amelogenin, or degraded
      amelogenin peptides, are removed from the extracellular matrix during enamel
      formation and maturation.

PMID- 17187174
TI  - Using a recombinant bispecific antibody to block Na+ -channel toxins protects
      against experimental scorpion envenoming.
AB  - In recent years, several molecular engineering methods of designing bispecific
      antibodies in various formats have been developed. Tandem-scFvs comprising two
      scFvs fused together via a peptide are 55-kDa molecules, and are one of the most
      promising and most straightforward approaches to bispecific antibody production.
      We report an attempt to design more effective antivenoms to the Androctonus
      australis scorpion using murine scFvs as building blocks to create a unique
      bispecific molecule that neutralizes the potent neurotoxins AahI and AahII. The
      tandem-scFv was produced in recombinant bacteria, purified by immobilized metal
      ion affinity chromatography, and analyzed by polyacrylamide gel electrophoresis,
      Western blot, gel filtration, mass spectrometry, and direct and competitive
      radioimmunoassay. In vivo, it neutralized the binding of the AahI and AahII
      toxins to their receptor, and protected mice against experimental envenomation.
      The findings reported here highlight the potential of recombinant antibody
      fragments for protecting against scorpion venom toxicity.

PMID- 17187175
TI  - The small heat shock proteins and their clients.
AB  - Small heat shock proteins are ubiquitous proteins found throughout all kingdoms.
      One of the most notable features is their large oligomeric structures with
      conserved structural organization. It is well documented that small heat shock
      proteins can capture unfolding proteins to form stable complexes and prevent
      their irreversible aggregation. In addition, small heat shock proteins
      coaggregate with aggregation-prone proteins for subsequent, efficient
      disaggregation of the protein aggregates. The release of substrate proteins from
      the transient reservoirs, i.e. complexes and aggregates with small heat shock
      proteins, and their refolding require cooperation with ATP-dependent chaperone
      systems. The amphitropic small heat shock proteins were shown to associate with
      membranes, although they do not contain transmembrane domains or signal
      sequences. Recent studies indicate that small heat shock proteins play an
      important role in membrane quality control and thereby potentially contribute to
      the maintenance of membrane integrity especially under stress conditions.

PMID- 17187176
TI  - The search for migraine genes: an overview of current knowledge.
AB  - Migraine is a complex familial condition that imparts a significant burden on
      society. There is evidence for a role of genetic factors in migraine, and
      elucidating the genetic basis of this disabling condition remains the focus of
      much research. In this review we discuss results of genetic studies to date, from
      the discovery of the role of neural ion channel gene mutations in familial
      hemiplegic migraine (FHM) to linkage analyses and candidate gene studies in the
      more common forms of migraine. The success of FHM regarding discovery of genetic
      defects associated with the disorder remains elusive in common migraine, and
      causative genes have not yet been identified. Thus we suggest additional
      approaches for analysing the genetic basis of this disorder. The continuing
      search for migraine genes may aid in a greater understanding of the mechanisms
      that underlie the disorder and potentially lead to significant diagnostic and
      therapeutic applications.

PMID- 17187177
TI  - p16 and p27 are functionally correlated during the progress of
      hepatocarcinogenesis.
AB  - The molecular mechanism of the cell-cycle machinery in hepatocellular carcinoma
      (HCC) has not yet been fully elucidated. Among the various types of cell-cycle
      regulators, p16 and p27 are now considered to be potent tumor suppressors. p16 is
      a G1-specific cell-cycle inhibitor that prevents the association of cyclin
      dependent kinase (CDK) 4 and CDK6 with cyclin D(1). Many studies have reported
      that p16 is inactivated not only in aggressive types of HCC but also in
      preneoplastic liver cirrhosis. In many cases of HCC, p16 is mainly inactivated by
      extensive CpG methylation, suggesting that epigenetic changes in the p16 gene may
      be important events during hepatocarcinogenesis. p27, an inhibitor of CDK2, is
      presently regarded as a potent adverse prognostic factor in many aggressive
      cancers. It should be noted that some cases of HCC show increased cell
      proliferation despite the expression of considerable amounts of p27. In these
      cases, p27 is inactivated by sequestration into cyclin D(1)-CDK4-containing
      complexes. Although the reason for the compositional changes in the p27
      containing complexes is unclear, our experimental results indicate that loss of
      p16 following DNA methylation is closely related to the functional inactivation
      of p27 in HCC. We suggest that assessment of the p16 status may be useful for a
      precise prognostic prediction for individuals with HCCs expressing high levels of
      p27.

PMID- 17187178
TI  - Mammalian cell nano structures visualized by cryo Hilbert differential contrast
      transmission electron microscopy.
AB  - We applied the Hilbert differential contrast phase electron microscopy technique
      for the first time to mammalian cells, Ptk2 cells. Intracellular architectures
      such as the cytoskeletal network, membranous organelles, and mitochondria were
      observed without prior removal of cell membranes or extraction of soluble
      proteins. The attachment of mitochondria and membrane organelles with
      microtubules were observed. Microtubules were depolymerized by nocodazole
      treatment as expected. Thus, Hilbert differential contrast phase electron
      microscopy of vitrified cells is a nano-scale molecular imaging technique that
      opens up new vistas for exploring the supramolecular organization of the
      mammalian cell.

PMID- 17187179
TI  - Uptake of microparticles into the epithelium of human nasopharyngeal lymphoid
      tissue.
AB  - The M cells of nasopharyngeal lymphoid tissue (NALT) have been considered to play
      an important role for vaccine delivery systems in humans. A number of
      investigations have reported particle uptake data in NALT of rodents. However,
      there have been no reports indicating any involvement of the nasopharyngeal
      lymphoid tissue in human vaccination. In the present study, we investigated
      whether the epithelium of human adenoid tissues might incorporate fluorescent
      microparticles using electron and fluorescent microscopy. The dissected adenoid
      tissues were incubated with various sizes and concentrations of fluorescent
      microparticles for 120 min at 37 degrees C. Furthermore, the effect of surface
      coatings of microparticles with cations on the uptake into the epithelium of
      adenoid tissues was investigated. Transmission electron microscopy revealed that
      microparticles were taken up by the M cells of human nasopharyngeal lymphoid
      tissues. The NALT-M cells showed greater uptake of the smallest particles, 0.2
      microm in diameter, than those of 0.5, 1.0, or 2.0 microm diameter. It was also
      revealed that surface coatings with poly-L: -lysin or chitosan resulted in
      efficient uptake into the NALT. These results indicate that nasal administration
      of antigenic microparticles, which were coated with cationic materials, probably
      leads to a useful method of transnasal vaccination against respiratory and
      intestinal infections in humans.

PMID- 17187180
TI  - Interaction between mesothelial cells and macrophages in the initial process of
      pleural adhesion: ultrastructural studies using adhesion molecules.
AB  - Detachment of mesothelial cells is an early step in adhesion of the human pleura.
      To elucidate this process, we used adhesion molecules as the targets of primary
      antibody and performed immunohistochemical staining of the mesothelial cells that
      cover the surface of the sites of pleural adhesion and the macrophages that
      migrate from connective tissue. The surface of the adhesion site that was formed
      as a result of edematous and villiform elongation of the connective tissue
      underlying the visceral pleura was covered with mesothelial cells. However, there
      was partial detachment of the mesothelial cells caused by adherence to
      macrophages that had migrated from within the connective tissue, and that
      adherence was mediated by adhesion molecules. We demonstrated that both
      mesothelial cells and macrophages each express both CD54 and CD11a, important
      adhesion molecules. It was surmised that the detachment of the mesothelial cells
      is the result of interaction with the macrophages via those adhesion molecules
      and that over time it progresses to pleural adhesion.

PMID- 17187181
TI  - Morphological alterations in the growth plate cartilage of ovariectomized mice.
AB  - The effects of ovariectomy on growth and estrogen receptor (ER) expression level
      in the epiphyseal growth plate in mice have been estimated by histomorphometry
      and immunohistochemistry. Twelve female ddY mice, 8-9 weeks of age, were
      subjected to bilateral ovariectomy and 12 others were sham operated. They were
      then killed 8 weeks later. Ovariectomy significantly increased the total
      thickness of the distal femoral and proximal tibial growth plate cartilage.
      Ovariectomy caused a 1.4-fold increase in the thickness of the proliferative
      layer in the distal growth plate of the femur and a 1.3-fold increase in the
      thickness of the proliferative layer in the proximal growth plate of the tibia.
      ERalpha and ERbeta immunoreactivity was detected in chondrocytes of the growth
      plate and the expression level of ERs in epiphyseal plates was increased in
      ovariectomized mice compared with controls. These data suggest that ERalpha and
      ERbeta are coexpressed in the growth plates of the mice and that the cartilage
      growth and the level of expression of ERs in these tissues are hormonally
      regulated.

PMID- 17187182
TI  - An ultrastructural study on the ligamentum flavum of the cervical spine in
      patients with ossification of the posterior longitudinal ligament.
AB  - Some histological analyses of the ossification of the posterior longitudinal
      ligament (OPLL) have been reported, but no ultrastructural studies of the
      ligamentum flavum (LF) in patients with OPLL have been published to date. To
      understand the pathology of the ossification of the spinal ligament, we examined,
      by electron microscopy, ultrastructural changes in the LF in cases of OPLL and
      made a comparison with the LF in cervical spondylotic myelopathy (CSM). Subjects
      were three men and two women with cervical OPLL who underwent longitudinal
      spinous process-splitting laminoplasty. During surgery, a small piece of the LF
      was collected from C2-C3 to C7-T1 and was then analyzed by light and electron
      microscopy. We observed atrophic elastic bundles with a two-layer structure and
      disarrangement, a partially torn area, the disappearance of microfibrils, and an
      enlarged interstitium with an irregular alignment of collagen fibrils. We
      observed some properties of a cell preceding its death: the initial phase may be
      the disappearance of the plasma-membrane, followed by the scattering of many
      organellae around its degenerated nucleus. Finally, many extracellular plasma
      membrane-invested particles that resemble matrix vesicles remain there without
      phagocytosis. These results suggest that ultrastructural abnormalities exist in
      the spinal ligament in cases of ossification of the spinal ligament.

PMID- 17187183
TI  - LPS-induced transient testicular dysfunction accompanied by apoptosis of
      testicular germ cells in mice.
AB  - The aim of this study was to clarify effects of inflammation on spermatogenesis
      in LPS-administered mice. ICR mice were treated by intraperitoneal injection for
      7 days with either physiological saline (control) or 0.1 mg lipopolysaccharide
      (LPS)/kg body weight/day. Control mice were killed at 24 h after the last
      injection and the LPS-treated group after 24 h or 1, 3, or 5 weeks. Sperm
      concentration and motility in the cauda epididymis were examined as well as
      immunohistochemical localization of Fas and FasL and germ cell apoptosis. Sperm
      concentration and motility markedly fluctuated in LPS-treated mice. Increase of
      apoptotic cells was common in all post-LPS treatment groups, with a peak at 24 h
      after LPS injection. In contrast to the lack of Fas immunoreactivity in control
      testes, LPS-treated groups demonstrated Fas in many germ cells, especially in
      spermatocytes and spermatids. Immunoreactivity for FasL, on the other hand, was
      positive for some Sertoli cells, Leydig cells, and germ cells in both control and
      LPS-treated groups at all time points. The results suggest that the Fas/FasL
      system mediates apoptosis of germ cells in LPS-treated mice testes. LPS
      administered mice thus provide a good experimental model for the study of
      transient disruption of spermatogenesis.

PMID- 17187184
TI  - CAM5.2-positive subserosal myofibroblasts in appendicitis.
AB  - In this study, we examined the distribution and origin of myofibroblasts around
      the perforations of appendicitis. Stromal cells of 45 cases were studied by
      immunohistochemistry. In the normal appendix, myofibroblasts were restricted to
      the mucosa, and CD34-positive stromal cells were distributed in the submucosal
      and subserosal layers. Some mesothelial cells were positive for cytokeratin
      CAM5.2, cytokeratin 5, or mesothelial cells (HBME-1). In perforation of
      appendicitis with both abscess and granulation tissue, a small to moderate or a
      moderate to large number of myofibroblasts appeared in the subserosal area around
      the perforation, respectively, but CD34-positive stromal cells were completely
      absent there. In the subserosal area of the perforation of appendicitis with
      abscess, cytokeratin 5-positive stromal cells were absent. However, a small to
      moderate number of cytokeratin CAM5.2-positive stromal cells were observed there.
      Double immunostaining showed the coexpression of alpha-smooth muscle actin (ASMA)
      and cytokeratin CAM5.2 and the coexpression of cytokeratin 5 and cytokeratin
      CAM5.2 in many or some stellate-shaped or spindle-shaped stromal cells existing
      in the subserosal area with granulation tissue around the perforation of
      appendicitis, respectively. Finally, many myofibroblasts appearing in the
      subserosal area of the perforation of appendicitis may be derived from
      submesothelial cells or mesothelial cells.

PMID- 17187185
TI  - Ultrastructural study of nuclear inclusions immunohistochemically positive for
      surfactant protein A in pulmonary adenocarcinoma with special reference to their
      morphogenesis.
AB  - To investigate the fine-structural nature of nuclear inclusions immunopositive
      for surfactant protein A (SP-A) antibody staining, a detailed ultrastructural
      study was performed, as well as immunohistochemical examination of pulmonary
      adenocarcinomas. Surgically resected tumor specimens from 31 patients were
      examined by immunohistochemistry focused on reactivity to SP-A and thyroid
      transcription factor 1 (TTF-1) antibodies. Only cases with >5% positive nuclear
      inclusions in cancer cells were considered positive, some of which were examined
      by electron microscopy. Immunohistochemically, 6 of 31 cases were doubly positive
      for SP-A and TTF-1 antibodies. On electron microscopy, SP-A-positive nuclei
      contained diffuse or globular fine granular substance as inclusions. Both types
      of globular and diffuse inclusions were sometimes connected to the inner nuclear
      membrane, in association with fragmented or stacked membranous structures. The
      findings of this study suggested that nuclear inclusions positive for SP-A
      antibody staining in adenocarcinomas of the lung were derived from accumulated
      content in the perinuclear cistern resembling pseudoinclusion processes and
      composed of proteins antigenically cross-reactive with SP-A.

PMID- 17187186
TI  - Askin tumor with metastasis to the scalp: a histochemical, immunohistochemical
      and ultrastructural study.
AB  - A 29-year-old woman presented with facial edema, and imaging disclosed a tumor
      extending from the anterior chest wall to the anterosuperior aspect of the
      mediastinum. Transbronchial cytology of the primary tumor and biopsy of the
      metastatic scalp lesion were performed. Histologically, the tumor consisted of
      closely packed small round cells. The neoplastic cells generally had round
      nuclei, finely dispersed chromatin, and small to prominent nucleoli.
      Histochemically, the cytoplasm of the neoplastic cells contained abundant
      glycogen and stained with Grimelius silver. Immunohistochemically, the neoplastic
      cell membranes reacted with CD99 (MIC2) and the neoplastic nuclei reacted with
      Fli-1, but various other markers, including lymphocyte and skeletal muscle
      markers, were not detected. No neoplastic cells were also reactive for
      chromogranin A, synaptophysin, and neurofilament. Ultrastructurally, some
      neoplastic cells had delicate cytoplasmic processes and contained membrane-bound
      dense core granules in the cytoplasm. Even if results are immunohistochemically
      negative for neuroendocrine markers, the combination of immunohistochemistry of
      CD99 (MIC2) and Fil-1 may be useful in diagnosing Askin tumor or its metastatic
      lesion.

PMID- 17187187
TI  - Osteoporotic fractures in Asia: risk factors and strategies for prevention.

PMID- 17187188
TI  - Transplantation of skin fibroblasts expressing BMP-2 contributes to the healing
      of critical-sized bone defects.

PMID- 17187189
TI  - Infrared analysis of bones in magnesium-deficient rats treated with vitamin K2.
AB  - In this study, we compared the effects of vitamin K(2) menatetrenone on bone
      mechanical properties in rats fed a low-magnesium (Mg) diet. In addition, the
      mechanism of bone quality was examined using Fourier transform infrared imaging
      (FTIRI). Thirty 4-week-old male Wistar rats were divided into three groups:
      intact, low-Mg-control, and low-Mg-MK-4 groups. Rats in the low-Mg groups were
      given a diet containing 6 mg/100 g Mg (intact, 90 mg/100 g). After an 8-week
      treatment, the cortical bone mineral content (CtBMC), outer perimeter, and endo
      perimeter of the femoral diaphysis in the low-Mg-control group were significantly
      higher, while the maximum load (ML) and elastic modulus (EM) were 81% and 50% of
      those in the intact group, respectively (respectively, P < 0.05). In the low-Mg
      MK-4 group, ML and EM were significantly higher than in the low-Mg-control group
      (P < 0.05), with no differences in CtBMC. The mineral/matrix ratios for the
      periosteal and central regions in the low-Mg-control group were 162% and 120% of
      those in the intact group (both, P < 0.05), respectively. MK-4 significantly
      inhibited these increases (P < 0.05). We found that the mineral/matrix ratios for
      the periosteal region of the femoral diaphysis were negatively correlated with
      EM, suggesting that an increase in the mineral/matrix ratio may be involved in
      the reduction of EM and that MK-4 may improve EM by improving the mineral/matrix
      ratio.

PMID- 17187190
TI  - Production of IL-7 is increased in ovariectomized mice, but not RANKL mRNA
      expression by osteoblasts/stromal cells in bone, and IL-7 enhances generation of
      osteoclast precursors in vitro.
AB  - Osteoclastogenic cytokines produced by T and B lineage cells and interleukin (IL)
      7-induced expansion of the pool size of osteoclast precursors have been suggested
      to play an important role in acceleration of osteoclastogenesis induced by
      estrogen deficiency. However, the contribution of increased RANKL produced by
      osteoblasts/stromal cells to increase osteoclastogenesis in a mouse model of
      estrogen-deficient osteoporosis and in vitro effects of IL-7 on osteoclast
      precursor generation remain controversial. Thus, we investigated the effect of
      ovariectomy (OVX) of mice on production of RANKL, osteoprotegerin (OPG), and IL-7
      in bone and the effect of IL-7 on osteoclast precursor generation in vitro. OVX
      did not significantly stimulate mRNA expressions of RANKL and OPG in whole
      femurs. Because the epiphysis, but not the femoral shaft (diaphysis) or bone
      marrow, is the main site of osteoclastogenesis, it is important to specifically
      analyze mRNA expression by osteoblasts/stromal cells at these parts of the femur.
      Therefore, we isolated RNA from bone marrow cell-free epiphysis, diaphysis, and
      flushed-out bone marrow and examined mRNA expression. The results showed no
      significant changes of RANKL and OPG mRNA expression in any part of the femur. In
      addition, OVX did not significantly affect RANKL and OPG mRNA expression by the
      adherent stromal cells isolated from flushed-out bone marrow cells but did
      stimulate RANKL mRNA expression by B220(+) cells in the nonadherent cell
      fraction. On the other hand, OVX increased IL-7 mRNA expression in the femur as
      well as IL-7 concentrations in bone fluid. In cultures of unfractionated bone
      cells isolated by vigorous agitation of minced whole long bones to release the
      cells tightly attached to the bone surfaces, but not in cocultures of clonal
      osteoblasts/stromal cells and flushed-out bone marrow cells, IL-7 stimulated
      generations of osteoclasts as well as osteoclast precursors. These data suggest
      that increased RANKL production by osteoblasts/stromal cells is unlikely to play
      a central role in acceleration of osteoclastogenesis in estrogen deficiency of
      mice and that IL-7 stimulates osteoclast precursor generation, presumably through
      an action of IL-7 on the cells attached to bone rather than on cells contained in
      the bone marrow cell population.

PMID- 17187191
TI  - The long-term effects of ovariectomy on bone metabolism in sheep.
AB  - Osteoporosis and associated fractures are major public health concerns, and as
      such require appropriate large animal models to further our understanding of this
      disease. Although sheep appear to be an ideal model with which to study bone loss
      caused by estrogen depletion, limited data are available concerning the long-term
      effect of ovariectomy on bone in sheep. The goal of the present study was to
      observe the ovariectomy-induced changes in bone mass, structure, and metabolism
      in sheep over a period of 18 months. Six ewes were ovariectomized (OVX) and
      compared to an age-matched control group by analyzing bone mineral density,
      trabecular structure, biochemical markers of bone formation and resorption, and
      plasma estrogen levels. Bone loss (13%, P < 0.01) occurred during the first 4
      months after surgery, then stabilized and returned to pre-OVX levels for the
      remainder of the study. Trabecular architecture was also altered and tended
      toward osteopenia with recovery to baseline values. Markers of bone formation and
      resorption were elevated up to 6 months postovariectomy, after which time levels
      returned to baseline values. Although estradiol measurements demonstrated a clear
      decline following surgical ovariectomy, levels returned to normal after 6 months.
      Therefore, the detrimental effect of ovariectomy on sheep bone metabolism seems
      to be reversible, with normal bone parameters being reestablished within 6 months
      after surgery. These data seem to indicate that the sheep is not an appropriate
      model for human postmenopausal osteoporosis.

PMID- 17187193
TI  - Effect of vitamin K2 and growth hormone on the long bones in hypophysectomized
      young rats: a bone histomorphometry study.
AB  - The purpose of the present study was to determine whether vitamin K(2) and growth
      hormone (GH) had an additive effect on the long bones in hypophysectomized young
      rats. Forty-eight female Sprague-Dawley rats (6 weeks old) were assigned to the
      following five groups by the stratified weight randomization method: intact
      controls, hypophysectomy (HX) alone, HX + vitamin K(2) (30 mg/kg, p.o., daily),
      HX + GH (0.625 mg/kg, s.c., 5 days a week), and HX + vitamin K(2) + GH. The
      duration of the experiment was 4 weeks. HX resulted in a reduction of the
      cancellous bone volume/total tissue volume (BV/TV) at the proximal tibial
      metaphysis, as well as decreasing the total tissue area and cortical area of the
      tibial diaphysis. These changes resulted from a decrease of the longitudinal
      growth rate and the bone formation rate (BFR)/TV of cancellous bone, as well as a
      decrease of the periosteal BFR/bone surface (BS) and an increase of endocortical
      bone turnover (indicated by the BFR/BS) in cortical bone. Administration of
      vitamin K(2) to HX rats did not affect the cancellous BV/TV or the cortical area.
      On the other hand, GH completely prevented the decrease of total tissue area and
      cortical area in cortical bone, as well as the decrease of marrow area and
      endocortical circumference, by increasing the periosteal BFR/BS compared with
      that in intact controls and reversing the increase of endocortical bone turnover
      (BFR/BS). However, GH only partly improved the reduction of the cancellous BV/TV,
      despite an increase of the longitudinal growth rate and BFR/TV compared with
      those of intact controls. When administered with GH, vitamin K(2) counteracted
      the reduction of endocortical bone turnover (BFR/BS) and circumference caused by
      GH treatment, resulting in no significant difference of marrow area from that in
      untreated HX rats. These results suggest that, despite the lack of an obvious
      effect on bone parameters, vitamin K(2) normalizes the size of the marrow cavity
      during development of the bone marrow in young HX rats treated with GH.

PMID- 17187192
TI  - Characterization of osteoclasts derived from CD14+ monocytes isolated from
      peripheral blood.
AB  - Bone resorption is solely mediated by osteoclasts. Therefore, a pure osteoclast
      population is of high interest for the investigation of biological aspects of the
      osteoclasts, such as the direct effect of growth factors and hormones, as well as
      for testing and characterizing inhibitors of bone resorption. We have established
      a pure, stable, and reproducible system for purification of human osteoclasts
      from peripheral blood. We isolated CD14-positive (CD14+) monocytes using anti
      CD14-coated beads. After isolation, the monocytes are differentiated into mature
      osteoclasts by stimulation with macrophage colony-stimulating factor (M-CSF) and
      receptor activator of nuclear factor kappaB ligand (RANKL). Osteoclast formation
      was only observed in the CD14+ population, not in the CD14- population, and only
      in the presence of both M-CSF and RANKL, confirming that the CD14+ system is a
      pure population of osteoclast precursors. No expression of osteoclast markers was
      observed in the absence of RANKL, whereas RANKL dose-dependently induced the
      expression of cathepsin K, tartrate-resistant acid phosphatase (TRACP), and
      matrix metallo proteinase (MMP)-9. Furthermore, morphological characterization of
      the cells demonstrated that actin rings were only formed in the presence of
      RANKL. Moreover, the osteoclasts were capable of forming acidic resorption
      lacunae, and inhibitors of lysosomal acidification attenuated this process.
      Finally, we measured the response to known bone resorption inhibitors, and found
      that the osteoclasts were sensitive to these and thereby provided a robust and
      valid method for interpretation of the effect of antiresorptive compounds. In
      conclusion, we have established a robust assay for developing osteoclasts that
      can be used to study several biological aspects of the osteoclasts and which in
      combination with the resorption marker CTX-I provides a useful tool for
      evaluating osteoclast function in vitro.

PMID- 17187194
TI  - Positive associations of bone mineral density with body mass index, physical
      activity, and blood triglyceride level in men over 70 years old: a TCVGHAGE
      study.
AB  - It is known that osteoporosis decreases physical function in older males.
      However, the role of metabolic parameters and physical activity influencing older
      men's bone status remains unclear. Thus, this study was designed to evaluate
      calcaneus bone mass by ultrasonic screening and the associated physical and
      metabolic functions in older men. This was a cross-sectional study. Three hundred
      sixty-eight older men (average age, 78.8 years) living in a veterans' home were
      enrolled. We measured body height and weight, waist and hip circumference, body
      fat, lean body mass, blood pressure, 6-min walking distance, complete blood
      count, and blood biochemical profile. Broadband ultrasound attenuation (BUA) and
      T-score were recorded using Soundscan quantitative ultrasound over the right
      calcaneus. The range of calcaneus BUA was 27.3-134.0; T-score was from -4.78 to
      3.43. Of the total participants, 36.4% were osteopenic (-2.5 < T-score < -1.0)
      and 16.3% were osteoporotic (T-score <or= -2.5). BUA correlated with weight, body
      mass index (BMI), waist circumference, hip circumference, body fat, lean body
      mass, serum triglycerides, high-density lipoprotein-cholesterol, albumin,
      prealbumin, fasting and PC-2h blood insulin, red blood cell count, hemoglobin
      concentration, and 6-min walking distance. Multiple regression stepwise analysis
      revealed that only BMI, distance of 6-min walking, and blood triglyceride level
      were independently and positively associated with the values of BUA. Calcaneus
      bone mass is significantly and positively associated with BMI, blood
      triglycerides, and 6-min walking distance in older men.

PMID- 17187195
TI  - Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system in
      patients with beta-thalassemia major.
AB  - Osteoporosis represents an important cause of morbidity in patients with beta
      thalassemia major, and its etiology is multifactorial. Thus, the aim of this
      study was to characterize the possible role of the osteoprotegerin (OPG) and
      receptor activator of the NF-kappaB ligand (RANKL) system in thalassemia-related
      bone loss. Serum concentrations of OPG, soluble RANKL (s-RANKL), markers of bone
      turnover, and lumbar spine bone mineral density (BMD) were measured in random
      samples of males (n = 29; mean age +/- SEM, 24.26 +/- 1.29 years; range, 13-41
      years) and females (n = 31; age, 24.59 +/- 0.95 years; range, 12-34 years) with
      beta-thalassemia major and in 30 healthy age-, height-, and weight-matched
      subjects. Thalassemic patients had significantly lower levels of OPG compared
      with controls (2.54 +/- 0.12 vs. 3.25 +/- 0.122, respectively; P < 0.05) and
      higher, albeit not statistically significantly, serum levels of s-RANKL (0.350 +/
      0.03 vs. 0.295 +/- 0.046, respectively; P < 0.05). s-RANKL correlated negatively
      with age (r = -0.3, P < 0.05), and OPG correlated positively with the duration of
      the interval between the onset of transfusions and chelation therapy (r = 0.52, P
      < 0.001). Regarding markers of bone metabolism, plasma values of osteocalcin
      correlated positively with s-RANKL (r = 0.40, P < 0.05) and negatively with OPG/s
      RANKL ratio (r = -0.55, P < 0.01). In multiple regression analysis only cross
      linked N-teleopeptide of type I collagen (NTX) significantly accounted for BMD.
      Although the OPG/RANKL system may have some clinical usefulness as a marker of
      bone turnover in beta-thalassemia, conventional markers of bone turnover more
      accurately represent changes in the BMD of these patients.

PMID- 17187196
TI  - Postural stabilizing effect of alfacalcidol and active absorbable algal calcium
      (AAA Ca) compared with calcium carbonate assessed by computerized posturography.
AB  - Sway and postural instability have drawn attention as a risk factor for
      osteoporotic fracture, in addition to low bone mineral density (BMD) and poor
      bone quality. In view of the fracture-reducing effect of alfacalcidol and active
      absorbable algal calcium (AAA Ca) not readily explained by rather mild increases
      of BMD, attempts were made to evaluate postural stabilizing effect of
      alfacalcidol, AAA Ca, and calcium carbonate (CaCO(3)) by computerized
      posturography. Track of the gravity center was analyzed to calculate parameters
      related to tract length, track range, and track density to express the degree of
      sway before and after supplementation in 126 subjects ranging in age between 20
      and 81 years randomly divided into four groups. Supplementation with AAA Ca
      containing 900 mg elemental Ca (group A), no calcium (group B), CaCO(3) also
      containing 900 mg elemental Ca (group C), or alfacalcidol (group D) continued
      daily for 12 months. For each parameter, the ratio closed eye value/open eye
      value (Romberg ratio) was calculated to detect aggravation of sway by eye
      closure. Age, parameters of Ca and P, and proportions of subjects with fracture
      and those with low BMD showed no marked deviation among the groups. With eyes
      open, significant decreases of a track range parameter (REC) from group B was
      noted in groups A (P = 0.0397) and D (P = 0.0296), but not in group C according
      to multiple comparison by Scheffe, indicating superior postural stabilizing
      effect of A and D over C. In the first 2 months, a significant fall was already
      evident in REC from group B in group D (P = 0.0120) with eyes open. Paired
      comparison of sway parameters before and after supplementation revealed a
      significant increase of track density parameter (LNGA), indicating sway control
      efficiency and a significant decrease of REC in groups A and D compared to group
      B with eyes open. With eyes closed, only group A showed a significant improvement
      from group B (P = 0.0456; Fig. 1), with a significant shortening on paired
      After/Before comparison (P = 0.0142; Fig. 2). Computerized posturography appears
      to be useful in analyzing sway phenomena especially as to the effects of vitamin
      D and various Ca preparations.

PMID- 17187197
TI  - Annual change in bone mineral density in predialysis patients with chronic renal
      failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D.
AB  - Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The
      aim of this study was to examine how a decrease in renal function affects annual
      bone mineral density (BMD) changes in predialysis CRF patients and to examine the
      factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF
      patients (age, 61.3 +/- 10.8 years; serum creatinine 2.7 +/- 1.2 mg/dl) was
      measured by peripheral quantitative computed tomography (pQCT) twice with a 1
      year interval. The total BMD of the radius significantly decreased over a year (P
      < 0.001), and both trabecular and cortical BMD showed a significant decrease.
      Significant positive correlations with BMD changes were found for estimated
      creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)(2)D (r =
      0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger
      reductions in creatinine clearance and serum 1,25(OH)(2)D. Of several bone
      metabolic markers examined, baseline serum osteocalcin was significantly
      positively correlated with annual BMD changes (r = -0.276, P < 0.05). Multiple
      regression analysis showed that baseline serum 1,25(OH)(2)D (beta = 0.434) was a
      significant predictor of decreases in total and trabecular BMD (R (2) = 0.188, P
      < 0.01; and R (2) = 0.207, P < 0.01), independent of other confounding factors.
      These results indicate that BMD decreases as renal function deteriorates in
      predialysis CRF patients, and that osteocalcin is a clinically useful marker
      associated with the decrease in BMD. The serum 1,25(OH)(2)D level is the
      principal factor affecting BMD of the radius, suggesting that supplementation
      with an active form of vitamin D is of importance for predialysis CRF patients.

PMID- 17187198
TI  - Primary structural modules of the dorsal nuclei of the thalamus and motor cortex
      in humans.
AB  - The aim of the present work was to study the primary structure of the modular
      organization of neurons in the dorsal nucleus of the thalamus (ventral anterior,
      ventral lateral, anterior ventral, anterior medial, anterior dorsal, medial,
      reticular) and motor cortex (fields 4 and 6) in humans by the Nissl, Kluver
      Barrera, and Golgi silver nitrate impregnation methods. These studies showed that
      neurons in the dorsal nuclei of the thalamus and the motor cortex are organized
      as small groups and short chains fulfilling defined criteria. These neuronal
      complexes, forming individual structural units, were termed primary structural
      modules. Comparison of primary structural modules in the dorsal nuclei and motor
      cortex showed that the principles of organization were identical in both
      locations. Thus, the dorsal nuclei of the thalamus and motor cortex in humans
      show two principles of the organization of neurons into primary structural
      modules: the group and chain principles.

PMID- 17187199
TI  - Regeneration of the rat spinal cord after thoracic segmentectomy: growth and
      restoration of nerve conductors.
AB  - The results presented in our previous report (Morfologiya, 127, No. 2 (2005))
      provided evidence that consolidation of the spinal cord (SC) after thoracic
      segmentectomy in rats occurs as a result of the formation of a connective tissue
      scar, which is quicker when the defect is filled with collagen gel. The present
      report describes analysis of semithin sections and transmission electron
      microscopy studies demonstrating that regenerating nerve conductors traverse
      connective tissue in structures whose organization is identical to that of
      peripheral nerves. In the zone of SC rarefaction caudal to the trauma site,
      myelination of growing axons is mediated by glial cells without the formation of
      nerve trunks. Large numbers of fine regenerating conductors were seen at the
      sites of degenerated myelin fibers in the fasciculi of the white matter in the
      lumbar segments of the SC.

PMID- 17187200
TI  - Morphometric characteristics of epitheliocytes in the choroid plexus of the
      cerebral ventricles in humans during aging.
AB  - Morphometric studies of villous epitheliocytes of the choroid plexus of the
      lateral (glomus) and third and fourth (lateral zone) ventricles of the brain were
      undertaken in humans aged from 22 to 89 years. Cell height, width, and cross
      sectional area were measured, along with the cross-sectional areas of nuclei and
      cytoplasm for calculation of the nucleus:cytoplasm ratio. These studies showed
      that epitheliocytes were of variable shape depending on their locations on the
      surfaces of villi. Epitheliocyte height and the cross-sectional areas of the
      cytoplasm and cells were greatest in the choroid plexus of the lateral ventricle,
      while the cross-sectional area of the nucleus and the nucleus:cytoplasm ratio
      were greatest in the choroid plexus of the fourth ventricle; these features
      correlate with their functional characteristics. Aging is associated with
      decreases in the sizes of epitheliocytes and their nuclei and a reduction in the
      nucleus:cytoplasm ratio, with the development of adaptive rearrangements.

PMID- 17187201
TI  - The role of nitric oxide in the apoptosis of neurons in the retina of the human
      fetal eye.
AB  - The locations of NADPH-diaphorase (NADPH-d), inducible NO synthase (iNOS), and
      TUNEL-immunoreactive neurons in the retina of human fetuses collected during the
      first to third trimesters of pregnancy were studied. High levels of NADPH-d
      activity were seen in the inner segments of light-sensitive cells, amacrine
      cells, and ganglion cells. The population of NADPH-d-positive amacrine cells
      included three types of neuron. Type 1 neurons were large and had sparse
      dendritic fields occupying the inner nuclear and outer retinal layers. Small type
      2 neurons were located in the inner retinal layer. Ectopic amacrine cells, type
      3, were located in the outer part of the ganglion layer. A high density of NADPH
      d-positive neurons was seen in the central part of the retina, surrounding the
      central fovea and optic disk area. NADPH-d activity increased progressively
      during ontogenesis and correlated with the appearance of immunoreactive iNOS in
      neurons. iNOS labeled a subpopulation of amacrine and ganglion cells, which
      appeared at 20-21 weeks of development and reached a peak of immunoreactivity by
      the end of the third trimester. TUNEL-immunopositive neuron nuclei with signs of
      apoptotic destruction were seen at 30-31 weeks of pregnancy. The greatest
      apoptotic index was seen in the ganglion and amacrine cell populations. These
      data identify NO as a factor mediating apoptosis of neurons during the critical
      period of differentiation of interneuronal connections in the human retina.

PMID- 17187202
TI  - Discussion of the sensory innervation of the brain.
AB  - In response to a commentary from another author, the present investigator
      provides new data obtained in his laboratory on the similarity of a number of
      brain neurons bearing asynaptic dendrites and innervating the perivascular space,
      the pia mater (from within), and making direct contact with the cerebrospinal
      fluid in the ventricles on the one hand with local intramural autonomic Dogiel
      type II neurons in the internal organs on the other. Our own electron microscopy
      data on the terminals of asynaptic dendrites in the brain are presented, these
      showing no difference in terms of ultrastructure from the terminals of receptors
      in the internal organs. Factual data are presented which, in the author's
      opinion, refute the other author's views that cilia in general and ciliated
      neurons in particular cannot have a variety of receptor functions, that sensory
      neurons arise exclusively from the neural crest, and that it is fundamentally
      impossible for brain tissues to have sensory innervation.

PMID- 17187203
TI  - Prophylactic treatment of migraine with topamax: long-term results.

PMID- 17187204
TI  - Antibodies to acetylcholine receptors in patients with different clinical forms
      of myasthenia and Lambert-Eaton myasthenic syndrome.

PMID- 17187205
TI  - Interaction between changes in local and temporospatial spectral EEG
      characteristics during exposure of humans to hypoxia.
AB  - The temporospatial and local characteristics of the EEG were studied in healthy
      subjects during the respiration of a hypoxic oxygen-nitrogen gas mixture
      containing 8% oxygen. Analysis of the spectral power density, coherence, phase
      shift, similarity of dominant frequencies in the EEG in different leads was
      performed separately for epochs containing and not containing visually apparent
      patterns of EEG spatial synchronization. In addition, assessment of spectral
      measures took account of the fact of the dominance of the frequency being
      analyzed in the EEG spectrum of the corresponding lead. The results of these
      studies showed that overall, hypoxia was accompanied by a decrease in EEG
      coherence in the alpha range and, for connections in the left mid-temporal lead,
      the delta range. The beta range showed an increase in the values of this measure,
      while the theta range showed different changes in coherence: increases in epochs
      containing spatial synchronization patterns and decreases from control levels in
      other epochs. Hypoxia was also associated with increases in the EEG phase shift
      in the frontal and temporal leads (in relation to the EEG recordings in the other
      leads) in the delta and theta ranges. In the beta range, conversely, there was a
      decrease in the mean phase shift. Consideration of the fact of dominance of one
      or another frequency in the spectra of local EEG traces is needed for correct
      interpretation of analyses of temporospatial measures. A mathematical model of
      the interaction between processes at different frequencies is presented to
      explain some of the observations in the current work.

PMID- 17187206
TI  - Involvement of dopamine D1 and D2 receptors in the rat nucleus accumbens in
      immunostimulation.
AB  - Analysis of the nature of changes in the immune response in operated Wistar rats
      showed that electrolytic lesioning of the nucleus accumbens, the site of the
      greatest density of dopamine D1 and D2 receptors, led to suppression of the
      immune response in animals immunized with sheep erythrocytes. Administration of
      SKF 38393 (20 mg/kg) and quinpirol (1 mg/kg), selective agonists of dopamine D1
      and D2 receptors respectively, to sham-operated rats induced significant
      increases in immune responses. However, no immunostimulation was seen on
      administration of the selective dopamine D2 agonist quinpirol to animals with
      lesions to the nucleus accumbens as compared with controls. At the same time,
      treatment of animals with nucleus accumbens lesions using the dopamine D1
      receptor agonist SKF 38393 had no effect on the immune response as compared with
      that in sham-operated animals given the D1 receptor agonist. These data provide
      evidence that dopamine D2 receptors in the nucleus accumbens have a role in the
      mechanisms of immunostimulation, though D2 receptors in other brain structures
      may also make some contribution to this process; D1 receptors in the nucleus
      accumbens make no significant contribution to controlling the immune response.

PMID- 17187207
TI  - Changes in the functioning of the electromechanical connection during tetanic
      contraction.
AB  - The functioning of the electromechanical connection during tetanic contraction in
      frog skeletal muscle was studied. Analysis using caffeine, calcium-free medium,
      the ryanodine receptor blocker dantrolene, and the Ca-ATPase inhibitor
      thapsigargin showed that the initial increase in tetanus, as in twitch
      contractions, did not require the presence of calcium ions in the surrounding
      medium, which is in agreement with published data. Contraction was accompanied by
      activation of potential-dependent release of calcium from the sarcoplasmic
      reticulum. In contrast, the secondary rise phase and/or the duration of the
      tetanus plateau were critically dependent on the present of Ca2+ in the
      surrounding medium. Given that contraction in this situation was inhibited by
      dantrolene, activation of prolonged contraction was also mediated by calcium
      released from the sarcoplasmic reticulum, though ryanodine receptors were now
      activated not by changes in the membrane potential but by the influx of external
      calcium. Thus, external calcium plays a significant role in the formation of
      prolonged contractile responses, providing for longer-lasting maintenance of
      power in contracted muscles.

PMID- 17187208
TI  - Molecular dynamics of rhodopsin and free opsin: computer simulation.
AB  - Computer simulation was used to perform a comparative study of the molecular
      dynamics of rhodopsin containing the chromophore group (11-cis-retinal) and free
      opsin. The molecular dynamics were followed over a time interval of 3000 psec; a
      total of 3 x 10(6) discrete conformational states of rhodopsin and opsin. The
      presence of the chromophore group in the chromophore center of opsin was shown to
      have significant effects on the immediate protein environment of the chromophore
      and the conformational state of the cytoplasmic domain, but to have virtually no
      effect on the conformational state of the intradisk domain. The simulation
      results are used to discuss the possible intramolecular mechanism by which
      rhodopsin is maintained as a G-protein-coupled receptor in the inactive state,
      i.e., the function of the chromophore as an effective antagonist ligand.

PMID- 17187210
TI  - Significance of peripheral feedback in the generation of stepping movements
      during epidural stimulation of the spinal cord.
AB  - Acute experiments on decerebrate and spinal cats were performed to study the role
      of the peripheral afferent input from hindlimb receptors in forming the locomotor
      pattern during epidural stimulation of the spinal cord. Evoked electromyographic
      activity in the muscles of the hindlimbs was analyzed, along with the kinematic
      parameters of stepping movements. Epidural stimulation (20-100 microA, 5 Hz) of
      segments L4-5 of the spinal cord was found to elicit well coordinated walking in
      the hindlimbs on a moving treadmill band. When the support conditions were
      changed (non-moving treadmill, unsupported position), epidural stimulation
      initiated walking with an unstable rhythm. This was associated with a change in
      the overall nature of the locomotor pattern and the internal structure of the
      stepping cycle. Alteration of the direction of movement of the treadmill band led
      to the appearance of backward walking. An increase in the speed of movement of
      the treadmill band increased the stepping frequency, mainly due to decreases in
      the extensor phase. Epidural stimulation applied 2-4 h after complete transection
      of the spinal cord at the T8-T9 level could elicit stepping movements, but only
      when the treadmill was moving. The role of peripheral feedback in generating the
      locomotor pattern in conditions of complete disconnection from supraspinal
      control increased significantly. These data show that peripheral feedback during
      epidural stimulation of the spinal cord can define the properties of the motor
      output.

PMID- 17187209
TI  - Effects of the action of microwave-frequency electromagnetic radiation on the
      spike activity of neurons in the supraoptic nucleus of the hypothalamus in rats.
AB  - Acute experiments on white rats anesthetized with Nembutal (40 mg/kg, i.p.) were
      performed with extracellular recording and analysis of background spike activity
      from neurons in the supraoptic nucleus of the hypothalamus after exposure to
      electromagnetic radiation in the millimeter range. The distribution of neurons
      was determined in terms of the degree of regularity, the nature of the dynamics
      of neural streams, and the modalities of histograms of interspike intervals; the
      mean neuron spike frequency was calculated, along with the coefficient of
      variation of interspike intervals. These studies demonstrated changes in the
      background spike activity, predominantly affecting the internal structure of the
      spike streams recorded. The major changes were in the duration of interspike
      intervals and the degree of regularity of spike activity. Statistically
      significant changes in the mean spike frequencies of neuron populations in
      individual frequency ranges were also seen.

PMID- 17187211
TI  - Central and peripheral thermoreceptors. Comparative analysis of the effects of
      prolonged adaptation to cold and noradrenaline.
AB  - This report presents results obtained from many years of study of the effects of
      prolonged adaptation to cold and noradrenaline on the spike activity of central
      hypothalamic and peripheral skin thermoreceptors. The involvement of the
      sympathetic nervous system in forming adaptive changes in the regulatory
      characteristics of temperature homeostasis and the significance of the various
      components of thermoreceptor activity to the formation of effector responses are
      discussed. The roles of different groups of thermoreceptors in forming
      temperature sensations are analyzed.

PMID- 17187216
TI  - Sexology and epidemiology.

PMID- 17187212
TI  - Unusual cause of persistent abdominal pain in a young girl: solid-pseudopapillary
      tumour of the pancreas (2006: 11b).
AB  - A solid-pseudopapillary tumour, a rare disease of the pancreas, in a young woman
      is presented. Since treatment involves complete excision of the mass, an early
      diagnosis is crucial to allow the curative resection.

PMID- 17187217
TI  - Sex of experimenter and social norm effects on reports of sexual behavior in
      young men and women.
AB  - Past studies indicate that men generally report having had more sexual experience
      and sexual partners than women, as well as an earlier age at first intercourse.
      At least some of these findings may partially reflect different responses to
      certain contextual variables in research. College students (266 men and 463
      women) were asked to anonymously report their sexual attitudes and behavior after
      reading one of three fictitious statements about research findings regarding
      gender differences in sexuality. Some past findings were replicated, with men
      reporting somewhat more sexual experience and more permissive sexual attitudes
      than women. However, women reported a significantly younger age at first
      intercourse than did men. While there was no significant sex difference for total
      number of sexual partners, there was a significant interaction. With female
      research assistants (but not with male assistants), men reported more sexual
      partners when they were told that women are now more sexually permissive than
      men. This finding appeared to be largely a function of the men who scored higher
      on measures of hypermasculinity and ambivalent sexism. Women's reports were not
      significantly affected by the wording of the cover sheet, regardless of the sex
      of the research assistant. Even in this anonymous survey, the sex of the
      experimenter and the nature of the statement about research findings had an
      impact on the sex differences that were found. In light of these results, some
      previous conclusions about male-female differences in sexual behavior may need to
      be examined more closely.

PMID- 17187218
TI  - Selling sex in a population-based study of high school seniors in sweden:
      demographic and psychosocial correlates.
AB  - Adolescents reporting selling sex for payment were studied with respect to
      socioeconomic background, perceived mental health and health behavior, antisocial
      behavior, sexual experiences, including sexual abuse and abusive behaviors, and
      the use of pornography. The sample consisted of a representative sample of 4,339
      students (response rate, 77.2%) from the third year of upper secondary schools in
      five Swedish cities. Of the participating adolescents, 1.8% of the boys and 1.0%
      of the girls indicated that they had sold sex for money or other reimbursements.
      Selling sex was associated with having an immigrant background, higher level of
      unemployment in the family, and studying a practical/vocational program.
      Adolescents with the experience of selling sex had an increased risk for
      different psychosocial problems, such as poorer mental health, weekly use of
      alcohol, and antisocial behaviors. The adolescents selling sex were also
      characterized by having had a greater number of sexual experiences, a greater
      preoccupation with sex, relatively early sexual debut, and experience with sexual
      abuse as victim and/or perpetrator. The index group students watched pornography
      more frequently than the majority and they also watched more deviant forms of
      pornography. The significance of the higher frequency among boys and the gray
      zone between normal sexual exploration and prostitution are discussed.

PMID- 17187219
TI  - Sexual practices and sexual satisfaction: a population based study of Chinese
      urban adults.
AB  - This study examined sexual satisfaction and its social and behavioral correlates
      among urbanites aged 20-64 in China, using data from a nationally representative
      sample of 1,194 women and 1,217 men with a spouse or other long-term sexual
      partner with whom they had sex during the last year. The results from structural
      equation models suggest a multiplex set of determinants of sexual satisfaction,
      including relationship characteristics, sexual knowledge and personal values,
      physical vitality, and environmental impediments. A large proportion of the
      effect of these background characteristics was mediated by frequent orgasms,
      varied sexual practices, and perceived partner affection. In particular, much of
      the effect of knowledge and beliefs was mediated through variety in sexual
      practices. While many of the observed patterns were shared among women and men,
      much of the effect of relationship characteristics was mediated through perceived
      partner affection for women. Men, in contrast, paid greater attention to his
      partner's physical attractiveness and to her extramarital sex. A sexual
      transition is well underway in urban China, even if more rapidly for men than for
      women. While knowledge and values are arguably more important in this
      transitional period, many antecedents of sexual well-being drawn from the
      literature on sexual behavior in developed Western countries are also applicable
      to urban China.

PMID- 17187220
TI  - Ascertaining consumer perspectives of medication information sources using a
      modified repertory grid technique.
AB  - OBJECTIVE: To establish the range of medicine information sources used by
      consumers and their perception of the reliability of these, using the repertory
      grid technique. METHOD: Consumers visiting three community pharmacies in
      Brisbane, Australia, were interviewed using the repertory grid technique. During
      the interview, consumers were asked to name up to three medicine information
      sources that they used for a supermarket medicine, an over-the-counter medicine
      and a prescription medicine. They were then presented with their named
      information sources in groups of three and asked to discriminate between these in
      terms of their perceived reliability of the information source. The descriptors
      used by the consumer to discriminate between the information sources are known as
      constructs and these were recorded. The consumer was then asked to rate each of
      their information sources against each generated construct. MAIN OUTCOME MEASURE:
      The range of information sources generated was determined along with the
      perceived reliability of these from the calculated median score of each
      information source when rated on each generated construct. RESULTS: A total of
      110 consumers were interviewed and identified 648 information sources that they
      would use. The most frequent information sources cited by the 110 consumers were
      their doctor (83%), written information (90%) and the pharmacist (78%). There
      were a total of 299 constructs generated by 88 of the consumers and these were
      themed into 16 discrete categories. The most common generated constructs themes
      were "good knowledge" (15%), "training" (14%) and "trustworthiness" (13%). The
      consumer perception of their information sources were that the doctor and
      pharmacist have good knowledge (median score 1) and are trained (median score 1)
      and were perceived to be trustworthy (median score 3 and 2, respectively).
      CONCLUSION: The repertory grid technique was successful in identifying the
      information sources consumers accessed to find out about their medicines and in
      identifying the perception of these sources in terms of their reliability. The
      repertory grid technique offers a novel method for future research into consumer
      preferences for different treatment options.

PMID- 17187221
TI  - Prioritising drug and therapeutics committee (DTC) decisions: a national survey.
AB  - OBJECTIVE: A national survey was conducted to explore stakeholder opinions about:
      (1) the domains of activity and criteria used to determine "important" decisions;
      (2) the "importance" of Drug and Therapeutics Committee (DTC) decisions as an
      appropriate approach for prioritising implementation and actions and (3) how DTC
      decisions could be prioritised for action. SETTING: This is a study of DTCs
      conducted in the Australian health care setting. METHODS: A semi-structured
      questionnaire was sent to Directors of Pharmacies or Chief Pharmacists in
      Australian hospitals. Questionnaires could be returned by email or by fax. Two
      weeks after initial mail-out, non-responders were followed-up. Responses were
      collated and analysed using descriptive statistics. Free-text responses were
      collated. QSR NVivo was used as a data management tool. RESULTS: The response
      rate was 61%. All respondents indicated that "patient safety" was a domain of
      importance for a decision. Other domains of important DTC decisions include:
      "ensuring the practice of evidence based medicine within their institution"
      (94%), "cost" (93%), "ensure practice according to legislative requirements"
      (87%). Most respondents agreed that some DTC decisions were more important than
      others. Given constraints on time and resources, the majority agreed that DTC
      decisions should be prioritised for implementation, although most had no
      suggestions about how this could be done. Some suggested that the domains of
      importance could be the basis for priority assignment. CONCLUSION: Currently DTC
      decisions and policies are implemented in an ad hoc manner. As a result
      implementation may be incomplete and ineffective, and may pose a risk of serious
      consequences in patient care. This study identifies the domains or criteria of
      DTC decisions so that DTCs may allocate scarce resources to the systematic
      implementation of important decisions.

PMID- 17187223
TI  - Determinants of potential drug-drug interaction associated dispensing in
      community pharmacies in the Netherlands.
AB  - OBJECTIVE: There are many drug-drug interactions (D-DI) of which some may cause
      severe adverse patient outcomes. Dispensing interacting drug combinations should
      be avoided when the risks are higher than the benefits. The objective of this
      study was to identify determinants of dispensing undesirable interacting drug
      combinations by community pharmacies in the Netherlands. METHODS: A total of 256
      Dutch community pharmacies were selected, based on the dispensing of 11
      undesirable interacting drug combinations between January 1st, 2001 and October
      31st, 2002. These pharmacies were sent a questionnaire by the Inspectorate for
      Health Care (IHC) concerning their process and structure characteristics. MAIN
      OUTCOME MEASURE: The number of times the 11 undesirable interacting drug
      combinations were dispensed. RESULTS: Two hundred and forty-six questionnaires
      (response rate 96.1%) were completed. Dispensing determinants were only found for
      the D-DI between macrolide antibiotics and digoxin but not for the other 10 D
      DIs. Pharmacies using different medication surveillance systems differed in the
      dispensing of this interacting drug combination, and pharmacies, which were part
      of a health care centre dispensed this interacting drug combination more often.
      CONCLUSION: Medication surveillance in Dutch community pharmacies seems to be
      effective. Although for most D-DIs no determinants were found, process and
      structure characteristics may have consequences for the dispensing of undesirable
      interacting drug combinations.

PMID- 17187222
TI  - Self-reported medication and lifestyle adherence in Hungarian patients with Type
      2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is a complex disorder that requires the patient to
      pay constant attention to diet, physical activity, glucose monitoring and
      medication. OBJECTIVE: To evaluate the medication, lifestyle adherence and
      factors associated to these in Type 2 diabetes in Hungarian patients. SETTING:
      Fourteen community pharmacies in Hungary between March and May 2004. METHOD: A
      questionnaire was given to every tenth Type 2 diabetic patient who presented to
      one of the 14 pharmacies included in this study with a prescription for oral
      antidiabetics, oral antidiabetics and insulin or exclusively insulin. For the
      latter two groups, the prerequisite for inclusion in the study was also that
      their diabetes had developed after the age of 35 and that at some in their
      treatment regimen they had taken only oral antidiabetics. These latter two
      criteria were controlled in the patient's general practitioners' (GP) database.
      General and diabetes-related data were collected in the questionnaire, and the
      adherence and lifestyle of the participant were assessed. An adapted and
      validated Hungarian version of the EQ-5D (EuroQol Group, 1993) quality-of-life
      questionnaire was also included. Descriptive and chi(2) test statistical methods
      and two sample t-test were used. A significance level of P<0.05 was considered to
      be significant. MAIN OUTCOME MEASURE: Patient self-reported adherence to diet,
      physical activity, self monitoring of blood glucose, purchasing of drug(s), drug
      regimen, association of demographic factors, treatment, lifestyle and quality of
      life on adherence. RESULTS: Of the 220 questionnaires distributed to diabetic
      patients, 151 were returned, of which 142 were evaluated (nine did not satisfy
      the above-mentioned inclusion criteria). With respect to the factors assessed,
      sub-optimal adherence was assessed for: diet (76.8%), physical activity (33.8%),
      self-monitoring of blood glucose (81%), drug purchasing (20.4%) and drug taking
      (52.1%). Smokers comprised 14.8% of the respondents, while 8.5% were heavy
      drinkers. Fewer than five meals a day were eaten by 46.5% of the patients, and
      about 43.6% of the patients did not self-monitor blood glucose. The results
      indicate few significant associations between at least one of the four main areas
      of adherence (diet, physical activity, purchasing of drug(s), drug regimen) and
      body mass index, GP consultation frequency, quality-of-life parameters and EQ-5D
      index. CONCLUSION: The adherence of Hungarian Type 2 diabetics in some areas does
      not reach optimal levels, especially for diet, self-monitoring, drug purchasing
      and adherence to drug taking.

PMID- 17187224
TI  - Isolation, sequence analysis and expression profile of a novel porcine gene,
      NIP7, differentially expressed in the Longissimus dorsi muscle tissues from
      Meishan, Meishan x Large White cross and Large White pigs.
AB  - In order to detect the molecular mechanism of heterosis in pigs, the mRNA
      differential display technique was performed to investigate the differences in
      gene expression in the Longissimus dorsi muscle tissues from Meishan, Meishan x
      Large White cross and Large White pigs. One novel gene that was differentially
      expressed was identified using semi-quantitative reverse transcriptase polymerase
      chain reaction (RT-PCR) and its complete cDNA sequence was obtained using the
      rapid amplification of cDNA ends (RACE) method. The nucleotide sequence of the
      gene is not homologous to any of the known porcine genes. The sequence prediction
      analysis revealed that the open reading frame of this gene encodes a protein of
      180 amino acids that contains the conserved putative RNA-binding domain in
      PseudoUridine synthase and Archaeosine transglycosylase (PUA) and has high
      homology with the 60S ribosome subunit biogenesis protein NIP7 homolog of three
      species--human (98%), mouse (97%) and rat (96%)--so that it can be defined as
      swine 60S ribosome subunit biogenesis protein NIP7 homolog (NIP7). The tissue
      expression analysis indicated that the swine NIP7 gene is over expressed in
      muscle, heart, liver, fat, kidney, and lung, but weakly expressed in small
      intestine, ovary, and spleen. The genomic DNA sequence of swine NIP7 gene was
      finally amplified and result revealed that the swine NIP7 gene contains five
      exons and four introns. Our experiment is the first to establish the primary
      foundation for further research on the swine NIP7 gene.

PMID- 17187225
TI  - Molecular cloning and expression of glycoprotein IIb and IIIa.
AB  - OBJECTIVE: To amplify the cDNA genes of GPIIb, GPIIIa, then construct the
      eukaryotic expression carriers of GPIIb and GPIIIa respectively, finally
      establish CHO cell lines stably expressing GPIIb and GPIIIa. METHODS: Human
      erythroleukemia (HEL) cells were cultured for total RNA extraction. RT-PCR was
      accomplished using the specific GPIIb, GPIIIa primers designed according to
      Genbank by Primer 5, then each of cDNAs were obtained. The expressive vector
      pcDNA3.1(+) and PCR products were cut by NheI and HindIII, and then the
      fragements were directly cloned to pcDNA3.1(+) because of having the same
      adhesive ends. Then pcDNA3.1(+)IIb and pcDNA3.1(+)IIIa were transfected into CHO
      cells respectively by Lipofectamine 2000. The cell lines expressing GPIIb, GPIIIa
      were screened by G418. Then the Chinese hamster ovary (CHO) cell lines were
      examed through flow cytometry (FCM) and RT-PCR to detect the expression of GPIIb,
      GPIIIa in CHO cells. RESULTS: The cDNAs of GPIIb and GPIIIa were amplidied by RT
      PCR, and the pcDNA3.1(+)IIb and pcDNA3.1(+)IIIa were constructed respectively. By
      sequencing and double digestion, pcDNA3.1(+)IIb and pcDNA3.1(+)IIIa were all
      correct. Expression of GPIIb and GPIIIa were detected on transfected CHO cells by
      FCM and RT-PCR. CONCLUSIONS: (1) Succeeded in constructing pcDNA3.1(+)IIb,
      pcDNA3.1(+)IIIa. (2) Succeeded in getting the cell lines expressing GPIIb,
      GPIIIa.

PMID- 17187226
TI  - Economical parallel protein expression screening and scale-up in Escherichia
      coli.
AB  - A novel microfermentation and scale-up platform for parallel protein production
      in Escherichia coli is described. The vertical shaker device Vertiga, which
      generates low-volume high density (A(600) approximately 20) Escherichia coli
      cultures in 96-position deep-well plates without auxiliary oxygen
      supplementation, has been coupled to a new disposable shake flask design, the
      Ultra Yield flask, that allows for equally high cell culture densities to be
      obtained. The Ultra Yield flask, which accommodates up to 1 l in culture volume,
      has a baffled base and a more vertical wall construction compared to traditional
      shake flask designs. Experimental data is presented demonstrating that the Ultra
      Yield flask generates, on average, an equivalent amount of recombinant protein
      per unit cell culture density as do traditional shake flask designs but at a
      substantially greater amount per unit volume. The combination of Vertiga and the
      Ultra Yield flask provides a convenient and scalable low-cost solution to
      parallel protein production in Escherichia coli.

PMID- 17187227
TI  - Association of elevated GRP78 expression with increased lymph node metastasis and
      poor prognosis in patients with gastric cancer.
AB  - Glucose-regulated protein 78 (GRP78) has been implicated in the protection of
      tumor cells from cytotoxic damage and apoptosis and thus assists cells in
      survival under oxygen-deprivation and nutrient-stress conditions. However, its
      expression and potential role in gastric cancer development and progression have
      not been reported. In the present study, we determined the level of GRP78
      expression in the primary tumor in 86 cases of resected gastric cancer by using
      immunohistochemistry and analyzed the relationships between GRP78 and
      clinicopathological characteristics. We found that GRP78 was overexpressed in the
      tumor specimens when compared with the expression in adjacent tumor-free gastric
      mucosa. Furthermore, the level of GRP78 expression in both primary tumors and
      metastatic lymph nodes was inversely correlated with patient survival.
      Overexpression of GRP78 was directly correlated with Sp1 expression and increased
      lymph node metastasis. Knocking down GRP78 expression inhibited tumor cell
      invasion in vitro and growth and metastasis in a xenograft nude mouse model.
      Therefore, our data imply that dysregulated expression of GRP78 may contribute to
      the development and progression of gastric cancer.

PMID- 17187228
TI  - Recombinant human prothrombin kringle-2 inhibits B16F10 melanoma metastasis
      through inhibition of neovascularization and reduction of matrix
      metalloproteinase expression.
AB  - Angiogenesis, a multi-step process which involves endothelial cell proliferation,
      adhesion, migration, and basement membrane (BM) degradation, is essential for
      tumor metastasis. Here we show that recombinant human prothrombin kringle-2 (rk
      2) inhibited bovine capillary endothelial cell migration with an IC(50)
      (concentration for half maximal inhibition) of 38 nM and inhibited adhesion to
      extracellular matrix (ECM) proteins. Because tumor metastasis requires
      angiogenesis, we examined whether rk-2 could inhibit metastases induced by
      injection of B16F10 melanoma cells into mice. The results revealed that the
      metastatic tumors in mouse lung were markedly decreased in a dose-dependent
      manner and acute lung injury induced by B16F10 melanoma metastasis was diminished
      by systemic rk-2 treatment. In immunohistochemical analysis, rk-2 reduced
      expression of vascular endothelial growth factor, which is a potent angiogenic
      activator and neovascularization in the mouse lung. Also, rk-2 diminished the
      expression of matrix metalloproteinase-2 and -9 in the mouse lung which induces
      tumor metastasis and angiogenesis. These data suggest that inhibition of B16F10
      melanoma metastasis by rk-2 was caused by inhibition of neovascularization and
      reduction of matrix metalloproteinase expression.

PMID- 17187229
TI  - HOXD3-overexpression increases integrin alpha v beta 3 expression and deprives E
      cadherin while it enhances cell motility in A549 cells.
AB  - We have previously shown that transduction of HOXD3, one of homeobox genes, into
      human lung cancer A549 cells enhances cell motility, invasion and metastasis. In
      the present study, we examined the roles of integrin beta3 which was up-regulated
      by HOXD3-overexpression in the HOXD3-induced motility of A549 cells. We first
      established integrin beta3-transfectants and compared their motile activity to
      those of the HOXD3-transfected, control-transfected and parental cells by three
      different assays. The integrin beta3-transfectants as well as the HOXD3
      transfectants formed heterodimer with integrin alphav subunit, and showed highly
      motile activities assessed by haptotaxis or phagokinetic track assay compared to
      the control transfectants or parental cells. In vitro wound-healing assay
      revealed that migratory activities were graded as the HOXD3-transfectants > the
      integrin beta3-transfectants > the control transfectants or parental cells. E
      cadherin was expressed in the integrin beta3-transfectants but not expressed in
      the HOXD3-transfectants. An addition of function-blocking antibody to E-cadherin
      into the wound-healing assay promoted the migratory activity of the integrin
      beta3-transfectants, suggesting that E-cadherin prevented the cells from
      dissociating from the wound edges. These results indicate that increased
      expression of integrin alphav beta3 and loss of E-cadherin by HOXD3
      overexpression are responsible for the enhanced motility and dissociation.

PMID- 17187230
TI  - A novel orthotopic murine model provides insights into cellular and molecular
      characteristics contributing to human osteosarcoma.
AB  - As a reliable model for osteosarcoma is lacking, three human cell lines (SaOS-2,
      U2OS and 143B) were evaluated in cell-based assays for proliferation, adhesion,
      migration, invasion, anchorage-independent growth, angiogenesis, mineralised
      nodule formation, plasmid transfection and oligonucleotide transfection. Tumor
      take and metastasis after orthotopic injection of the three cell lines into mice
      was monitored. The levels of expression of typical bone markers were determined
      with semi-quantitative RT-PCR in cultured cells, primary tumors, and for the SaOS
      2 cell line, the metastases. Tumors grew and spread to the lungs within 3 and 5
      weeks respectively, mimicking the clinical progression of the disease as analysed
      by x-ray. Expression of molecular markers in SaOS-2 indicated a mostly
      differentiated cell type at the primary and secondary sites. The ability of
      osteosarcoma cells to interact with collagen-1 and to form mineralised deposits
      correlated positively with tumor aggression in vivo. Expression of alkaline
      phosphatase was a common theme in both tumor models at the primary site. The
      newly established SaOS-2 model should allow the testing of candidate anti
      osteosarcoma agents as well as dissection of more intricate mechanisms involved
      in human osteosarcoma.

PMID- 17187231
TI  - Some characteristics of the distribution of heavy metals in urban topsoil of
      Xuzhou, China.
AB  - An assessment is presented of distribution characteristics of heavy metals in the
      urban topsoil from the city of Xuzhou. The concentrations of Ag, Al, As, Au, Ba,
      Be, Bi, Cd, Co, Cr, Cu, Fe, Ga, Hg, Li, Mn, Mo, Ni, Pb, Pd, Pt, Sb, Sc, Se, Sn, V
      and Zn have been determined from 21 soil samples. Examination of lognormal
      distribution plots indicates that the diagrams of Al, Be, Fe, Ga, Li, and V are
      almost linear suggesting that these metals are almost unaffected by anthropogenic
      activities while the plots for As, Cd, Cu, Pb, Pd, Pt, Se, Zn and others are not
      linear probably due to anthropogenic activities from which these metals are
      delivered to the soils. Al is used for mineralogical normalization of these data.
      An evaluation of background values for topsoil is also carried out by means of
      lognormal distribution plots. The results show our background values obtained
      from the lognormal distribution plots are comparable to those values of
      uncontaminated soils of Xuzhou obtained by previous work except for Cd and Hg. At
      present, no explanation for the exceptions Cd and Hg can be given.

PMID- 17187232
TI  - Mutation analysis of five candidate genes in familial breast cancer.
AB  - Most of the known breast cancer susceptibility genes (BRCA1, BRCA2, CHEK2 and
      ATM) are involved in the damage response pathway. Other members of this pathway
      are therefore good candidates for additional breast cancer susceptibility genes.
      ATR, along with ATM, plays a central role in DNA damage recognition and Chk1
      relays checkpoint signals from both ATR and ATM. PPP2R1B and PPP2R5B code for
      subunits of protein phosphatase 2A (PP2A), which regulates autophosphorylation of
      ATM. In addition, EIF2S6/Int-6, which was originally identified as a common
      integration site for the mouse mammary tumour virus in virally induced mouse
      mammary tumours, is a candidate breast cancer susceptibility gene because of its
      putative role in maintaining chromosome stability. To investigate the role of
      ATR, CHK1, PPP2R1B, PPP2R5B and EIF2S6/Int-6, we carried out mutation analysis of
      these genes in the index cases from non-BRCA1/BRCA2 breast cancer families. We
      also screened sporadic breast tumours for somatic mutations in PPP2R1B and
      PPP2R5B. Although we identified many novel variants, we found no evidence that
      highly penetrant germline mutations in these five genes contribute to familial
      breast cancer susceptibility.

PMID- 17187233
TI  - Dendritic cells fused with allogeneic breast cancer cell line induce tumor
      antigen-specific CTL responses against autologous breast cancer cells.
AB  - Dendritic cell (DC)/tumor cell fusion vaccine has been revealed as a promising
      tool for the antitumor immunotherapy. Previous research has shown that fusion
      hybrids of human DCs and autologous tumor cells can induce cytotoxic T lymphocyte
      (CTL) responses against autologous tumor cells in animal models and human
      clinical trials. However, a major restriction factor for the clinical use is the
      difficulty for preparation of sufficient amount of autologous tumor cells
      especially for the patients with metastasis cancer whose primary tumor lesion is
      not clear or has been resected. In this study, allogeneic breast cancer cell line
      MCF-7 cells were electrofused to autologous DCs from patient with breast cancer
      as a strategy to deliver shared breast cancer antigens to DCs. Fusion cells
      generated by autologous DCs and allogeneic MCF-7 were able to induce autologous T
      lymphocytes proliferation, high levels of IFN-gamma production and CTL responses.
      CTLs induced by DCs/allogeneic MCF-7 fusion cells were able to kill autologous
      breast cancer cells in an antigen specific and HLA restriction manner. Our study
      may provide the experiment basis for the use of allogeneic breast cancer cell
      line in the DC/tumor cell fusion cell vaccination strategy.

PMID- 17187234
TI  - ESR1, AR, body size, and breast cancer risk in Hispanic and non-Hispanic white
      women living in the Southwestern United States.
AB  - Estrogen and androgen are thought to influence breast cancer risk. The actions of
      estrogens and androgens are mediated through the respective receptors. In this
      study we examine the association of the Xb1 polymorphism of estrogen receptor
      alpha (ESR1) and the CAG repeat of the androgen receptor (AR) gene with risk of
      breast cancer in women living in the Southwestern United States. Cases (N = 1169
      non-Hispanic white (NHW) and 576 Hispanic) with first primary breast cancer were
      matched to controls (N = 1330 NHW and 725 Hispanic) by location (Arizona,
      Colorado, New Mexico, or Utah) and 5-year age group. Detailed weight history was
      obtained along with other diet and lifestyle information. Neither the ESR1 nor
      the AR polymorphisms evaluated were associated independently with breast cancer
      risk in either Hispanic or NHW women. However, among Hispanic women taking
      hormone replacement therapy (HRT), there was a 40% reduced risk of breast cancer
      among women with an X allele (95% CI 0.39, 0.94). Also Hispanic women with the xx
      genotype had a significant reduced risk of breast cancer in the presence of
      weight gain prior to age 50 if post-menopausal or prior to diagnosis if pre
      menopausal (P interaction 0.02 and <0.01 respectively). These results suggest
      differences in risk factors for NHW and Hispanic women. However, they provide
      only minor support for the role of the AR and ESR1 gene in the etiology of breast
      cancer.

PMID- 17187235
TI  - JNK pathway regulates estradiol-induced apoptosis in hormone-dependent human
      breast cancer cells.
AB  - Estrogen is known to stimulate breast cancer development in humans. Ironically,
      high doses of estrogen can induce regression of hormone-dependent breast cancer
      in postmenopausal women. The mechanism by which estrogen induces tumour
      regression in breast cancer is still unknown. We found that under low growth
      stimulated conditions, high concentrations of 17-beta-estradiol (estradiol)
      induces apoptosis and concomitantly increases phosphorylation of c-jun in
      estrogen receptor (ER)-positive breast cancer cell line, MCF-7, but not in ER
      negative breast cancer cell line MDA-MB 231 suggesting an ER-mediated event.
      Interestingly, when the c-jun NH2-terminal kinase (JNK) signalling pathway was
      disrupted by the JNK inhibitor SP600125, the ability of estradiol to inhibit the
      growth of MCF-7 cells and to induce apoptosis was completely blocked. These data
      suggest that JNK plays a central role in mediating the anticancer effect of high
      concentrations of estradiol in MCF-7 cells. Our data showing the apoptotic effect
      of estradiol in low growth-stimulated conditions suggest potential implications
      for the pharmacological control of breast cancer with high dose estrogen in
      postmenopausal women. Furthermore, our results indicate that augmenting JNK
      activity could be an efficient novel approach for treating breast cancer.

PMID- 17187236
TI  - 29th Annual San Antonio Breast Cancer Symposium, December 14-17, 2006, San
      Antonio, Texas, USA. Abstracts.

PMID- 17187237
TI  - Directing RNA interference specifically to differentiated muscle cells.
AB  - A common approach for mediating RNA interference (RNAi) is to introduce DNA that
      encodes short hairpin RNA (shRNA), which is often contained in a plasmid that can
      express a shRNA in a wide variety of cell types. Muscle cells and certain other
      cell types grown in culture can exist in both a dividing state and in a post
      mitotic, differentiated state, and it is sometimes useful to induce RNAi
      selectively in terminally differentiated cells to study the function of a gene,
      particularly when the gene is also required for propagation of dividing cells. We
      describe two methods for studying gene function by RNAi specifically in
      terminally differentiated skeletal muscle cells in culture. We developed a shRNA
      expression vector, based on myosin light chain 1f gene regulatory sequences,
      which is designed to induce shRNA expression specifically after differentiation
      has been initiated. We show that this vector can mediate RNAi and is only active
      in differentiated muscle cells. Also, we developed an adenoviral vector that is
      designed to be able to deliver shRNAs directly to post-mitotic muscle cells. We
      show that adenoviruses produced using this vector mediate RNAi in differentiated
      muscle cells. These methods add to the repertoire of RNAi tools that can be used
      for identifying genes involved in any event of interest that occurs in
      differentiated muscle cells.

PMID- 17187238
TI  - Airborne particulate matter and premature deaths in urban Europe: the new WHO
      guidelines and the challenge ahead as illustrated by Spain.
AB  - Twenty first century epidemiological publications on urban air pollution are
      confirming that inhalation of fine, airborne particulate matter (PM) has serious
      chronic human health effects and is a major cause of premature death worldwide.
      Recently updated recommendations by WHO identify three "Interim Targets" for the
      stepped reduction in PM levels within world cities in the quest to achieve an
      annual mean Air Quality Guideline (AQG) concentration of 20 mug/m(3) for
      particles less than 10 microns in size (PM(10)). In this paper we offer a
      perspective from Spain, a country with the longest record of reporting pollution
      data from large numbers of urban traffic sites to a central European database
      (AIRBASE). We can demonstrate that average annual PM concentrations at urban
      traffic monitoring stations in many European cities continue to be 50-100% above
      the WHO AQG, a situation exacerbated by high urban PM(2.5/10) ratios which
      indicate a dominance of finer, more deeply inhalable particles potentially more
      detrimental to health. Given that WHO has estimated in 2000 there were well over
      250,000 premature deaths in Europe attributable to PM inhalation, such continuing
      high urban pollution levels are placing a huge burden on European medical
      resources.

PMID- 17187239
TI  - Chicken antibodies: a useful tool for antigen capture ELISA to detect bovine
      leukaemia virus without cross-reaction with other mammalian antibodies.
AB  - The 24 kDa protein from the gag of the bovine leukaemia virus was cloned and
      expressed as a fusion protein GST-p24. This recombinant protein was then used to
      immunize a Leghorn chicken. The partially purified chicken anti-GST IgY was used
      to develop a solid-phase assay by binding the IgY to an ELISA plate. When the
      fusion protein contacts the antibody, it binds it by its N-terminal, leaving the
      C-terminal, which carries the sequence that acts as a capture antigen in solution
      maximally exposed, reducing the risk of epitope masking. The conditions of the
      fusion protein on the solid phase maximize the presentation of the antigens'
      epitopes in solution. For the first time, a system has been developed with a non
      mammalian coating antibody. Besides optimizing the recognition of low-molecular
      weight antigens synthesized as fusion proteins, it avoids cross-reactions with
      commonly used secondary antibodies, mostly raised in mammalian hosts.

PMID- 17187240
TI  - Pharmacokinetics of eprinomectin in plasma and milk in lactating camels (Camelus
      dromedarius).

PMID- 17187241
TI  - Host switch of Lamellodiscus elegans (Monogenea: Monopisthocotylea) and
      Sparicotyle chrysophrii (Monogenea: Polyopisthocotylea) between cage-reared
      sparids.
AB  - Sharpsnout bream (Diplodus puntazzo) has been used in Adriatic aquaculture for
      less than a decade, but the decreasing trend of rearing this species will
      probably result in its complete substitution by more exploited sea bream (Sparus
      aurata). Only two facilities still rear both fish species in neighbouring cages
      in monoculture. A switch of parasites was observed between sparids during
      monitoring of the gill monogeneans of farmed fish. In wild fish of the Adriatic
      Sea, Lamellodiscus elegans (Monogenea: Monopisthocotylea) has previously been
      reported in annular (Diplodus annularis), and two-banded sea bream (D. vulgaris)
      and sharpsnout bream (D. puntazzo), and the present study confirmed its presence
      also in sea bream, in low prevalence and abundance. The exclusively sea bream
      monogenean Sparicotyle chrysophrii (Monogenea: Polyopisthocotylea) was also
      isolated from sharpsnout bream, showing prevalence and abundance values even
      higher than in its resident host. In the occurrence of L. elegans in sea bream,
      the opportunistic switch resulted in lower abundance and prevalence than in the
      original host, while in the second case of switching the monogenean S.
      chrysophrii showed better reproductive capacity on a new host (sharpsnout bream).
      Both cases point to the possible enlargement of parasite host range.

PMID- 17187242
TI  - Absence of severe recurrent infections in glycogen storage disease type Ib with
      neutropenia and neutrophil dysfunction.
AB  - We describe a 10-year-old boy with glycogen storage disease type Ib (GSD Ib) with
      neutropenia and neutrophil dysfunction who never suffered from severe recurrent
      infections. Lymphocyte subpopulations and assay of intracellular cytokines (IL-2,
      IL-4 and IFN-gamma) showed a pattern of lymphocyte activation suggesting a shift
      of T(H)1/T(H)2 balance towards a T(H)1 response. This is the first report of GSD
      Ib without severe recurrent infections in spite of neutropenia and neutrophil
      dysfunction.

PMID- 17187243
TI  - [Macrovascular secondary prevention with pioglitazone in diabetics. PROactive
      Study (PROspective pioglitAzone Clinical Trial In macroVascular Events)].

PMID- 17187244
TI  - [Concomitant cardiovascular conditions in intestinal illness].
AB  - Vascular diseases are not encountered very often in gastroenterology, though in
      cases of ischemic colitis a coronary heart disease is often present. In addition,
      heart diseases such as coronary heart disease, atrial fibrillation, and
      congestive heart failure are important risk factors for ischemic colitis and
      should be treated to avoid further ischemic episodes of the gut. The most common
      extraintestinal manifestations of Crohn's disease and ulcerative colitis are
      observed in the eye, on the skin, and in the liver region. Involvement of the
      cardiovascular system does not seem to be very common, though systematic
      epidemiological data on the significance of these extraintestinal complications-
      which certainly influence the prognosis--are lacking. Other patients with Crohn's
      disease or ulcerative colitis suffer from vasculitis, which reflects a further
      manifestation of inflammatory diseases affecting the cardiovascular system.
      Another important complication is activation of coagulationfactors, especially
      during active flare-up of intestinal disease; this can result in thromboembolic
      events. Systematic studies or investigations on the epidemiology of
      cardiovascular complications are still lacking, so that an overview of the
      published data is given. Metastatic tumors of the heart are rare, but there are
      case reports of cardiac metastases in patients with carcinomas of the colon.
      Carcinoid heart syndrome, another cardial complication of malignant disease, can
      prejudice the prognosis of patients with neuroendocrine tumors of the
      gastrointestinal tract.

PMID- 17187245
TI  - Comment on: Nathan DM, Buse JB, Davidson MB et al (2006) Management of
      hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and
      adjustment of therapy. A consensus statement from the American Diabetes
      Association and the European Association for the Study of Diabetes. Diabetologia
      49:1711-1721.

PMID- 17187246
TI  - Influence of diabetes and hyperglycaemia on infectious disease hospitalisation
      and outcome.
AB  - AIMS/HYPOTHESIS: Diabetes mellitus is believed to increase susceptibility to
      infectious diseases. The effects of hyperglycaemia per se on infectious disease
      risk are unknown and the influence of diabetes on infectious disease outcome is
      controversial. MATERIALS AND METHODS: We studied 10,063 individuals from the
      Danish general population, who were participants in The Copenhagen City Heart
      Study, over a follow-up period of 7 years. Risk of hospitalisation caused by any
      infectious disease, and subsequent risk of disease progression to death were
      estimated by Cox proportional hazards regression analysis. RESULTS: At baseline,
      353 individuals reported having diabetes. During 71,509 person-years of follow
      up, a total of 1,194 individuals were hospitalised because of an infection. The
      risk of pneumonia (adjusted hazard ratio [aHR] 1.75, 95% CI 1.23-2.48), urinary
      tract infection (aHR 3.03, 95% CI 2.04-4.49) and skin infection (aHR 2.43, 95% CI
      1.49-3.95) was increased in subjects with diabetes compared with subjects
      without. Each 1 mmol/l increase in plasma glucose at baseline was associated with
      a 6-10% increased relative risk of pneumonia, urinary tract infection and skin
      infection after adjustment for other possible confounders. Among patients
      hospitalised for urinary tract infection, diabetic patients were at an increased
      risk of death at 28 days after admission compared with non-diabetic subjects (HR
      3.90, 95% CI 1.20-12.66). CONCLUSIONS/INTERPRETATION: In the Danish general
      population, diabetes and hyperglycaemia are strong and independent risk factors
      for hospitalisation as a result of pneumonia, urinary tract infection and skin
      infection. Further, diabetes has a negative impact on the prognosis of urinary
      tract infection.

PMID- 17187247
TI  - Pre-eclampsia and the later development of type 2 diabetes in mothers and their
      children: an intergenerational study from the Walker cohort.
AB  - AIMS/HYPOTHESIS: Studies have shown a relationship between pre-eclampsia and
      later coronary artery disease. This study investigated whether there is a
      relationship between pre-eclampsia and the development of type 2 diabetes in
      mothers and their babies and how this is affected by infant birthweight. SUBJECTS
      AND METHODS: This was an intergenerational cohort study. The study population
      comprised 7,187 mothers who gave birth and 8,648 babies who were born in Dundee,
      Scotland between 1952 and 1958. Their later diabetic status was defined from 1980
      to 2003 by linkage to population-based datasets. RESULTS: There were 810 (11.3%)
      mothers with pre-eclampsia and 745 (10.4%) who subsequently developed type 2
      diabetes. Logistic regression showed an increased risk of developing type 2
      diabetes for mothers with pre-eclampsia, unadjusted odds ratio (OR) 1.37 (95% CI
      1.10-1.71), p=0.005. This relationship persisted after adjustment for infant
      birthweight, OR 1.40 (95% CI 1.12-1.75), p=0.003. Of the babies born between 1952
      and 1958, 221 (2.6%) had developed type 2 diabetes, 137 of them male (2.9% of
      male subjects in study population) and 84 female (2.2% of female subjects). The
      relationship between pre-eclampsia in the mother and the risk of type 2 diabetes
      in the offspring did not reach statistical significance, OR 1.38 (95% CI 0.90
      2.10). Babies with birthweight in the lowest quintile (adjusted for sex,
      gestation and birth order) had an increased risk of developing type 2 diabetes,
      OR for lowest quintile vs highest quintile 1.84 (95% CI 1.24-2.72), p=0.002.
      CONCLUSIONS/INTERPRETATION: Pre-eclampsia is associated with increased risk of
      developing type 2 diabetes in the mother, but birthweight is a more important
      determinant of future risk for the offspring.

PMID- 17187248
TI  - Placental growth factor-1 and epithelial haemato-retinal barrier breakdown:
      potential implication in the pathogenesis of diabetic retinopathy.
AB  - AIMS/HYPOTHESIS: Disruption of the retinal pigment epithelial (RPE) barrier
      contributes to sub-retinal fluid and retinal oedema as observed in diabetic
      retinopathy. High placental growth factor (PLGF) vitreous levels have been found
      in diabetic patients. This work aimed to elucidate the influence of PLGF-1 on a
      human RPE cell line (ARPE-19) barrier in vitro and on normal rat eyes in vivo.
      METHODS: ARPE-19 permeability was measured using transepithelial resistance and
      inulin flux under stimulation of PLGF-1, vascular endothelial growth factor
      (VEGF)-E and VEGF 165. Using RT-PCR, we evaluated the effect of hypoxic
      conditions or insulin on transepithelial resistance and on PLGF-1 and VEGF
      receptors. The involvement of mitogen-activated protein kinase (MEK, also known
      as MAPK)/extracellular signal-regulated kinase (ERK, also known as EPHB2)
      signalling pathways under PLGF-1 stimulation was evaluated by western blot
      analysis and specific inhibitors. The effect of PLGF-1 on the external haemato
      retinal barrier was evaluated after intravitreous injection of PLGF-1 in the rat
      eye; evaluation was by semi-thin analysis and zonula occludens-1
      immunolocalisation on flat-mounted RPE. RESULTS: In vitro, PLGF-1 induced a
      reversible decrease of transepithelial resistance and enhanced tritiated inulin
      flux. These effects were specifically abolished by an antisense oligonucleotide
      directed at VEGF receptor 1. Exposure of ARPE-19 cells to hypoxic conditions or
      to insulin induced an upregulation of PLGF-1 expression along with increased
      transcellular permeability. The PLGF-1-induced RPE cell permeability involved the
      MEK signalling pathway. Injection of PLGF-1 in the rat eye vitreous induced an
      opening of the RPE tight junctions with subsequent sub-retinal fluid
      accumulation, retinal oedema and cytoplasm translocation of junction proteins.
      CONCLUSIONS/INTERPRETATION: Our results indicate that PLGF-1 may be a potential
      regulation target for the control of diabetic retinal and macular oedema.

PMID- 17187249
TI  - Acute blockade by endothelin-1 of haemodynamic insulin action in rats.
AB  - AIMS/HYPOTHESIS: Plasma levels of endothelin-1 are frequently elevated in
      patients with hypertension, obesity and type 2 diabetes. We hypothesise that this
      vasoconstrictor may prevent full perfusion of muscle, thereby limiting delivery
      of insulin and glucose and contributing to insulin resistance. MATERIALS AND
      METHODS: The acute effects of endothelin-1 on insulin-mediated haemodynamic and
      metabolic effects were examined in rats in vivo. Endothelin-1 (50 pmol min(-1)
      kg(-1) for 2.5 h) was infused alone, or 30 min prior to a hyperinsulinaemic
      euglycaemic insulin clamp (10 mU min(-1) kg(-1) for 2 h). Insulin clamps (10 or
      15 mU min(-1) kg(-1)) were performed after 30 min of saline infusion. RESULTS:
      Endothelin-1 infusion alone increased plasma endothelin-1 11-fold (p < 0.05) and
      blood pressure by 20% (p < 0.05). Endothelin-1 alone had no effect on femoral
      blood flow, capillary recruitment or glucose uptake, but endothelin-1 with 10 mU
      min(-1) kg(-1) insulin caused a decrease in insulin clearance from 0.35 +/- 0.6
      to 0.19 +/- 0.02 ml/min (p = 0.02), resulting in significantly higher plasma
      insulin levels (10 mU min(-1) kg(-1) insulin: 2,120 +/- 190 pmol/l; endothelin-1
      + 10 mU min(-1)kg(-1) insulin: 4,740 +/- 910 pmol/l), equivalent to 15 mU min(-1)
      kg(-1) insulin alone (4,920 +/- 190 pmol/l). The stimulatory effects of
      equivalent doses of insulin on femoral blood flow, capillary recruitment and
      glucose uptake were blocked by endothelin-1. CONCLUSIONS/INTERPRETATION:
      Endothelin-1 blocks insulin's haemodynamic effects, particularly capillary
      recruitment, and is associated with decreased muscle glucose uptake and glucose
      infusion rate. These findings suggest that elevated endothelin-1 levels may
      contribute to insulin resistance of muscle by increasing vascular resistance and
      limiting insulin and glucose delivery.

PMID- 17187250
TI  - Genes involved in oxidative phosphorylation are coordinately upregulated with
      fasting hyperglycaemia in livers of patients with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Mitochondrial oxidative phosphorylation (OXPHOS) plays an
      important role in the pathophysiology of type 2 diabetes. Genes involved in
      OXPHOS have been reported to be down-regulated in skeletal muscle from patients
      with type 2 diabetes; however, hepatic regulation is unknown. MATERIALS AND
      METHODS: We analysed expression of genes involved in OXPHOS from the livers of 14
      patients with type 2 diabetes and 14 subjects with NGT using serial analysis of
      gene expression (SAGE) and DNA chip analysis. We evaluated the correlation
      between expression levels of genes involved in OXPHOS and the clinical parameters
      of individuals with type 2 diabetes and NGT. RESULTS: Both gene analyses showed
      that genes involved in OXPHOS were significantly upregulated in the type 2
      diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial
      transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and
      mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip
      analysis revealed that expression of genes involved in OXPHOS, which correlated
      with several nuclear factors, including estrogen-related receptor-alpha or
      peroxisome proliferator-activated receptor-gamma, was a predictor of fasting
      plasma glucose levels, independently of age, BMI, insulin resistance and fasting
      insulin levels (p = 0.04). Surprisingly, genes involved in OXPHOS did not
      correlate with peroxisome proliferator-activated receptor-gamma coactivator
      1alpha or nuclear respiratory factor 1. CONCLUSIONS/INTERPRETATION: Our results
      indicate that upregulation of genes involved in OXPHOS in the liver, which are
      regulated by different mechanisms from genes in the skeletal muscle, is
      associated with fasting hyperglycaemia in patients with type 2 diabetes.

PMID- 17187251
TI  - Plasma and cerebrospinal fluid pharmacokinetics of intravenously administered ABT
      751 in non-human primates.
AB  - PURPOSE: ABT-751 is an orally bioavailable sulfonamide that binds to the
      colchicine binding site on beta-tubulin and inhibits microtubule polymerization.
      The plasma and cerebrospinal fluid (CSF) pharmacokinetics of ABT-751, after a
      short intravenous infusion, were evaluated in a non-human primate (Macaca
      mulatta) model that is highly predictive of the CSF penetration of drugs in
      humans. MATERIALS AND METHODS: Plasma and CSF samples were collected over 24 h
      after 7.5 mg/kg (150 mg/m2) ABT-751 infused over 0.25-0.70 h, and ABT-751
      concentrations in plasma and CSF were quantified using a validated HPLC-MS/MS
      assay. Pharmacokinetic parameters in plasma and CSF were derived using non
      compartmental methods. RESULTS AND CONCLUSION: Plasma disappearance was bi
      exponential with a terminal half-life of 13 h. The mean +/- SD clearance was 100
      +/- 18 ml/min m2, the mean +/- SD volume of distribution at steady state was 1.3
      +/- 0.5 l/kg, and the mean +/- SD mean residence time was 4.6 +/- 1.8 h. The mean
      +/- SD peak ABT-751 concentration in CSF was 0.26 +/- 0.08 microM, and the mean
      +/- SD CSF half-life of 1.3 +/- 0.3 h. CSF penetration was limited (mean +/- SD
      AUC(CSF):AUC(plasma), 1.1 +/- 0.3%) relative to total (protein-bound + free)
      plasma drug concentrations, but the CSF concentrations approximated the estimated
      free drug concentrations in plasma.

PMID- 17187252
TI  - Effect of a V-ATPase inhibitor, FR202126, in syngeneic mouse model of
      experimental bone metastasis.
AB  - PURPOSE: It has been demonstrated that vacuolar ATPase (V-ATPase) is involved in
      various aspects of bone metastasis. The aim of this study is to investigate the
      effect of the anti-bone resorptive activity of the V-ATPase inhibitor FR202126 on
      bone metastases in mice with metastatic breast cancer. METHOD: As a spontaneous
      model of breast cancer metastasis to bone, mouse breast cancer cells, 4T1, were
      injected into the mammary fat pad in immunocompetent syngeneic mice. The mice
      were orally treated with FR202126 for 29 days. Tumor volume was measured once a
      week. Thirty days after the injection of the cells, the bone mineral density
      (BMD) of the proximal tibia was measured using peripheral quantitative computed
      tomography. Histomorphometric analysis of the distal femurs and the proximal
      tibiae was performed. To elucidate the mechanism behind the anti-osteolytic
      effect of FR202126, 4T1 cells were treated directly in vitro with FR202126. Cell
      viability was measured, and cell invasion was assessed using matrigel. RESULTS:
      Oral administration of FR202126 significantly increased BMD by reducing the
      eroded bone surface ratio. While FR202126 is known to potently inhibit osteoclast
      mediated bone resorption, it did not prevent invasion by cancer cells or their
      proliferation. CONCLUSION: The V-ATPase inhibitor FR202126 was found to be
      effective at ameliorating osteolysis induced by metastatic breast cancer, even
      when the cancer cells themselves are not significantly affected by it. These
      results suggest that the anti-bone resorptive effect of the V-ATPase inhibitor
      might be useful for treating bone metastases associated with breast cancer.

PMID- 17187254
TI  - New evidence of shared dinosaur across Upper Jurassic Proto-North Atlantic:
      Stegosaurus from Portugal.
AB  - More than one century after its original description by Marsh in 1877, we report
      in this paper the first uncontroversial evidence of a member of the genus
      Stegosaurus out of North America. The specimen consists of a partial skeleton
      from the Upper Jurassic of Portugal, herein considered as Stegosaurus cf.
      ungulatus. The presence of this plated dinosaur in the upper Kimmeridgian-lower
      Tithonian Portuguese record and synchronic levels of the Morrison Formation of
      North America reinforces previous hypothesis of a close relationship between
      these two areas during the Late Jurassic. This relationship is also supported by
      geotectonic evidences indicating high probability of an episodic corridor between
      the Newfoundland and Iberian landmasses. Together, Portuguese Stegosaurus
      discovery and geotectonic inferences could provide a scenario with episodical
      faunal contact among North Atlantic landmasses during the uppermost Kimmeridgian
      lowermost Tithonian (ca. 148-153 Ma ago).

PMID- 17187253
TI  - Flavopiridol synergizes TRAIL cytotoxicity by downregulation of FLIPL.
AB  - PURPOSE: Flavopiridol is known to modulate the transcription of genes. We
      investigated the effect of flavopiridol pretreatment on TRAIL cytotoxicity and on
      the expression of FLIP(L) in different TRAIL-resistant cell lines, because FLIP
      expression is known to confer TRAIL-resistance. METHODS: Apoptosis was assessed
      by PI staining and protein expression by Western blotting. RT-PCR was used for
      mRNA quantitation. siRNA gene silencing was used to knock down FLIP(L). RESULTS:
      Flavopiridol pretreatment synergized TRAIL-induced apoptosis in human myeloma and
      breast cancer cells. Flavopiridol treatment repressed the transcription of
      FLIP(L) and downregulated its expression in both myeloma and breast cancer cells.
      Silencing of FLIP(L) gene by siRNA sensitized myeloma cells to TRAIL.
      Flavopiridol treatment downregulated the expression of the proapoptotic members
      of the Bcl-2 family proteins (Bak, Bax and PUMA-alpha). The expression of the
      antiapoptotic Bcl-2 members (Bcl-2 and Bcl-X(L)) was not altered by flavopiridol
      treatment in myeloma cells. CONCLUSION: Our data indicate that flavopiridol
      synergizes TRAIL cytotoxicity by downregulation of FLIP(L) and this synergistic
      effect is Bcl-2 family independent.

PMID- 17187255
TI  - Uncoupling primer and releaser responses to pheromone in honey bees.
AB  - Pheromones produce dramatic behavioral and physiological responses in a wide
      variety of species. Releaser pheromones elicit rapid responses within seconds or
      minutes, while primer pheromones produce long-term changes which may take days to
      manifest. Honeybee queen mandibular pheromone (QMP) elicits multiple distinct
      behavioral and physiological responses in worker bees, as both a releaser and
      primer, and thus produces responses on vastly different time scales. In this
      study, we demonstrate that releaser and primer responses to QMP can be uncoupled.
      First, treatment with the juvenile hormone analog methoprene leaves a releaser
      response (attraction to QMP) intact, but modulates QMP's primer effects on
      sucrose responsiveness. Secondly, two components of QMP (9-ODA and 9-HDA) do not
      elicit a releaser response (attraction) but are as effective as QMP at modulating
      a primer response, downregulation of foraging-related brain gene expression.
      These results suggest that different responses to a single pheromone may be
      produced via distinct pathways.

PMID- 17187256
TI  - Treatment of difficult cases of systemic-onset juvenile idiopathic arthritis with
      tacrolimus.
AB  - Since a proportion of systemic-onset juvenile idiopathic arthritis (SOJIA)
      patients continue to require long-term corticosteroid therapy for disease
      control, an effective and safe therapeutic strategy for controlling the activity
      of refractory SOJIA remains to be established. We report the efficacy of
      tacrolimus for the treatment of SOJIA in two patients with refractory SOJIA, one
      of them showing poor response to cyclosporine A. Tacrolimus might be the
      treatment of choice in selected patients with refractory systemic-onset juvenile
      idiopathic arthritis. Further studies to confirm the long-term efficacy and
      safety of tacrolimus in larger numbers of patients are, however, needed.

PMID- 17187259
TI  - Rehabilitation and shoulder function after suprascapular nerve entrapment
      operation in a volleyball player.
AB  - The purpose of this report was to determine a detailed description of a
      rehabilitation programme of a volleyball player who had a decompression surgery
      for suprascapular nerve entrapment and to expose the long-term functional
      outcomes which lead to successful results.

PMID- 17187258
TI  - [Project "Partnership"--university surgical departments and hospitals for basic
      and regular medical care. Directing cooperation for the future].
AB  - Over the last 20 years, urgently needed changes in the German health care system
      have forced hospitals to make a flexible adjustment to rising costs and the
      single handed, almost unmanageable dynamics of technical innovation in medicine.
      The partnership between the Salem Hospital and the Heidelberg University Hospital
      represents a pioneering management concept for the future. The alliance between a
      university surgical department with a basic peripheral hospital provides large
      advantages to patients, staff, hospitals and cost carriers.

PMID- 17187257
TI  - ADAMTS13 phenotype in plasma from normal individuals and patients with thrombotic
      thrombocytopenic purpura.
AB  - The activity of ADAMTS13, the von Willebrand factor cleaving protease, is
      deficient in patients with thrombotic thrombocytopenic purpura (TTP). In the
      present study, the phenotype of ADAMTS13 in TTP and in normal plasma was
      demonstrated by immunoblotting. Normal plasma (n = 20) revealed a single band at
      190 kD under reducing conditions using a polyclonal antibody, and a single band
      at 150 kD under non-reducing conditions using a monoclonal antibody. ADAMTS13 was
      not detected in the plasma from patients with congenital TTP (n = 5) by either
      antibody, whereas patients with acquired TTP (n = 2) presented the normal
      phenotype. Following immunoadsorption of immunoglobulins, the ADAMTS13 band was
      removed from the plasma of the patients with acquired TTP, but not from that of
      normal individuals. This indicates that ADAMTS13 is complexed with immunoglobulin
      in these patients. The lack of ADAMTS13 expression in the plasma from patients
      with hereditary TTP may indicate defective synthesis, impaired cellular
      secretion, or enhanced degradation in the circulation. This study differentiated
      between normal and TTP plasma, as well as between congenital and acquired TTP.
      This method may, therefore, be used as a complement in the diagnosis of TTP.

PMID- 17187261
TI  - Surgeon satisfaction agreement after total knee arthroplasty using a visual
      analogue scale: a single surgeon series.
AB  - INTRODUCTION: The outcome of total knee arthroplasty (TKA) is traditionally rated
      by objective criteria such as the knee society clinical rating system (KSCRS).
      Subjective criteria, such as satisfaction, will be of more importance, because
      health-care is shifting towards a market model. The aim of this study was to
      investigate the agreement on satisfaction after TKA between two orthopaedics
      surgeons, when one of the surgeons reviews his own results. PATIENTS AND METHODS:
      We investigated a group of 57 patients (63 TKAs) using a visual analogue scale
      (VAS) for satisfaction. There were 53 TKAs available and were separately seen by
      the two orthopaedic surgeons for clinical follow-up. RESULTS: After we split the
      satisfaction rate as excellent-good and fair-poor (VAS smaller or equal to 20 was
      excellent-good), we found a substantial agreement (kappa = 0.77) between the
      orthopaedic surgeons. However, we found that the surgeon who viewed his own
      results (B) scored a significantly lower satisfaction than surgeon A when
      analysing the complete group. CONCLUSIONS: The interobserver agreement of
      satisfaction, using a VAS, was high between the two orthopaedic surgeons. The
      satisfaction VAS is a simple tool to quantify satisfaction of surgeons and
      patients after TKA and could be used to evaluate quality. Comparison between
      studies could be more efficient and reliable using the satisfaction VAS method.

PMID- 17187260
TI  - Sternoclavicular joint septic arthritis and mediastinitis. A case report and
      review of the literature.
AB  - Septic arthritis of the sternoclavicular joint is rare. Its causes have been
      reported to include immuno-compromizing diseases, intravenous drug abuse,
      fractures of the clavicle or catheterization of the subclavian vein. We report a
      case of septic arthritis of the SCJ in a diabetic patient following periarticular
      injection of steroids in the ipsilateral shoulder, as this route of infection has
      not been documented, to our knowledge, in the literature to date. We review the
      literature regarding epidemiology and methods of surgical treatment that have
      been proposed, and present our own surgical experience. Bacterial infection
      should always be suspected in cases of SCJ arthritis. If surgery is required, it
      is important to remember that bony procedures leave vascular structures exposed,
      making their cover by myoplasty mandatory.

PMID- 17187262
TI  - [The "Journal Club" in "Radiology": facts and opinions].

PMID- 17187263
TI  - [Advances in cardiovascular medicine through molecular imaging].
AB  - We will witness a change of paradigm in cardiovascular imaging, which is
      empowered by advances in imaging technology, biochemistry, molecular biology and
      nanotechnology. Instead of simply following the physical distribution of
      established contrast agents, we now have the opportunity to noninvasively image
      biological processes such as enzyme activity, interaction with cell surface
      markers, gene expression and cell migration. These advancements open up new
      avenues in basic cardiovascular research and will greatly speed up the pace of
      discovery. Patient management will profit as well: cardiovascular molecular
      imaging will strengthen personlized and prophylactic medicine through timely and
      precise diagnostics. In our review we describe selected molecular imaging
      strategies in atherosclerosis, myocardial ischemia and healing.

PMID- 17187265
TI  - Obesity hypoventilation syndrome: prevalence and predictors in patients with
      obstructive sleep apnea.
AB  - Patients with obesity hypoventilation syndrome (OHS) have a lower quality of
      life, more healthcare expenses, a greater risk of pulmonary hypertension, and a
      higher mortality compared to eucapnic patients with obstructive sleep apnea
      (OSA). Despite significant morbidity and mortality associated with OHS, it is
      often unrecognized and treatment is frequently delayed. The objective of this
      observational study was to determine the prevalence of OHS in patients with OSA
      seen at the sleep disorders clinic of a large public urban hospital serving
      predominantly minority population and to identify clinical--not mechanistic-
      predictors that should prompt clinicians to measure arterial blood gases. In the
      first stage, we randomly selected 180 patients referred to our sleep disorders
      clinic between 2000 and 2004 for suspicion of OSA. From this retrospective random
      sample we calculated the prevalence of OHS in patients with OSA and identified
      independent clinical predictors using logistic regression. In the second stage,
      we prospectively validated these predictors in a sample of 410 consecutive
      patients referred to the sleep disorders clinic for suspicion of OSA between 2005
      and 2006. The prevalence of OHS in patients with OSA was 30% in the retrospective
      random sample and 20% in the prospective sample. Three variables independently
      predicted OHS in both samples: serum bicarbonate level (p < 0.001), apnea
      hypopnea index (p = 0.006), and lowest oxygen saturation during sleep (p <
      0.001). Due to the serious morbidity associated with OHS, we selected a highly
      sensitive threshold of serum bicarbonate level. A threshold of 27 mEq/l had a
      sensitivity of 92% and a specificity of 50%. Only 3% of patients with a serum
      bicarbonate level <27 mEq/l had hypercapnia compared to 50% with a serum
      bicarbonate > or =27 mEq/l. In conclusion, OHS is common in severe OSA. A normal
      serum bicarbonate level excludes hypercapnia and an elevated serum bicarbonate
      level should prompt clinicians to measure arterial blood gases.

PMID- 17187264
TI  - [Cell tracking. Principles and applications].
AB  - Cell based therapies such as stem cell therapies or adoptive immunotherapies are
      currently being explored as a potential treatment for a variety of diseases such
      as Parkinson's disease, diabetes or cancer. However, quantitative and qualitative
      evaluation of adoptively transferred cells is indispensable for monitoring the
      efficiency of the treatment. Current approaches mostly analyze transferred cells
      from peripheral blood, which cannot assess whether transferred cells actually
      home to and stay in the targeted tissue. Using cell-labeling methods such as
      direct labeling or transfection with a marker gene in conjunction with various
      imaging modalities (MRI, optical or nuclear imaging), labeled cells can be
      followed in vivo in real-time, and their accumulation as well as function in vivo
      can be monitored and quantified accurately. This method is usually referred to as
      "cell tracking" or "cell trafficking" and is also being applied in basic
      biological sciences, exemplified in the evaluation of genes contributing to
      metastasis. This review focuses on principles of this promising methodology and
      explains various approaches by highlighting recent examples.

PMID- 17187266
TI  - Temporal and spatial variability in stable isotope compositions of a freshwater
      mussel: implications for biomonitoring and ecological studies.
AB  - Stable isotopes can be used to elucidate ecological relationships in community
      and trophic studies. Findings are calibrated against baselines, e.g. from a
      producer or primary consumer, assumed to act as a reference to the isotopic
      context created by spatio-temporal attributes such as geography, climate,
      nutrient, and energy sources. The ability of an organism to accurately represent
      a community base depends on how, and over what time-scale, it assimilates ambient
      materials. Freshwater mussels have served as references for trophic studies of
      freshwater communities and as indicators of change in nutrient pollution load or
      source. Their suitability as reference animals has not yet been fully explored,
      however. We conducted a series of studies examining the suitability of freshwater
      mussels as isotopic baselines, using their ability to reflect variation in
      ambient nutrient loads as a case scenario. (1) We analyzed bivalve foot tissue
      delta(15)N and delta(13)C from 22 stream reaches in the Piedmont region of North
      Carolina, USA to show that compositions varied substantially among locations.
      Site mean bivalve delta(13)C values correlated with site ambient particulate
      organic matter (POM) delta(13)C values, and site mean bivalve delta(15)N values
      correlated with site ambient water dissolved delta(15)N-NO(3) values. (2)
      Similarity of results among sample types demonstrated that the minimally invasive
      hemolymph sample is a suitable substitute for foot tissue in delta(15)N analyses,
      and that small sample sizes generate means representative of a larger population.
      Both findings can help minimize the impact of sampling on imperiled freshwater
      mussel populations. (3) In a bivalve transplantation study we showed that
      hemolymph delta(15)N compositions responded to a shift in ambient dissolved
      delta(15)N-NO(3), although slowly. The tissue turnover time for bivalve hemolymph
      was 113 days. We conclude that bivalves serve best as biomonitors of chronic,
      rather than acute, fluctuations in stream nutrient loads, and provide initial
      evidence of their suitability as time-integrated isotopic baselines for community
      studies.

PMID- 17187267
TI  - Is the CD14 C159T polymorphism effective in the development of secondary
      amyloidosis in Familial Mediterranean fever?
AB  - The most important complication of FMF is the development of amyloidosis. It is
      more common in the eastern Mediterranean compared to the US. The individual
      response to endotoxin may have a significant effect on the development of
      amyloidosis in FMF patients. To investigate the association between CD14 promotor
      C-159T polymorphism and development of amyloidosis, one hundred and forty-six
      patients who had FMF and had not developed amyloidosis; 26 with FMF and secondary
      amyloidosis and 92 controls were genotyped at the CD14-C159T locus. There was no
      difference between the genotype distribution of FMF patients (CC 30.0%, CT 50.0%,
      TT 20.0%) and controls (CC 29.2%, CT 45.8%, TT 25%); or between FMF patients with
      amyloidosis (CC 30.8%, CT 53.8%, TT 15.4%) or without amyloidosis (CC 29.2%, CT
      45.8%, TT 25%). Our study shows that the CD14-C159T polymorphism is not
      associated with FMF or development of amyloidosis in the population studied. The
      effect of the genetic variations in the endotoxin signaling pathway under
      different environmental conditions such as high and low endotoxin exposure remain
      to be determined.

PMID- 17187269
TI  - [Antidepressant effects of dopamine agonists. Experimental and clinical
      findings].
AB  - Results of preclinical and clinical studies implicate that, in addition to
      serotonin and norepinephrin, dopaminergic mechanisms play a role in the
      pathogenesis and treatment of depression. Newer antidepressants such as
      bupropion, sertraline, and venlafaxine act as partial inhibitors of presynaptic
      dopamine reuptake. Experimental studies show that dopaminergic effects contribute
      to the development of anxiety, depression, and anhedonia. These studies revealed,
      among the new nonergot dopamine agonists, anxiolytic properties for ropinirole
      and anxiolytic, antidepressive, and antianhedonic effects of pramipexole which
      seem to relate to its specific action on D(2) and D(3) receptors in the
      mesolimbic system and prefrontal cortex. In addition, affective disorders may be
      associated with impairments of neuronal plasticity, and pramipexole seems to
      exert neurotrophic properties. Controlled and open studies in depressed patients
      with Parkinson's disease show therapeutic effects of dopamine agonists on motor
      deficits, anhedonia, and depression. Various dopamine agonists have been tested
      in open studies in patients with depression and may add to the spectrum of
      treatment options in mood disorders. Recently published placebo-controlled trials
      in small patient groups implicate that pramipexole is effective as additional
      treatment to mood stabilizers in I and II bipolar depression.

PMID- 17187270
TI  - Mixed or metachronous germ-cell tumor?
AB  - OBJECTIVE AND IMPORTANCE: We report the extremely rare occurrence of a second
      germ-cell tumor at a different site and with different histological types long
      after total resolution of a pineal germinoma. CLINICAL PRESENTATION: A 21-year
      old man who presented with headache and diplopia was admitted to our hospital.
      Neuroradiological studies revealed a tumor in the pineal region. The tumor was
      biopsied with endoscope, and third ventriculostomy was performed. Histologically,
      the tumor proved to be a germinoma. The patient received 3 cycles of combination
      chemotherapy consisting of carboplatin and etoposide with radiotherapy. The tumor
      was totally resolute. Twelve months later, he was readmitted with headache and
      diplopia. Neuroradiological studies showed a tumor in the right temporal lobe.
      INTERVENTION: The second tumor was totally removed. Histologically, the tumor
      proved to be a mixed germ-cell tumor, which consisted a yolk-sac tumor and a
      germinoma. After the second course of chemotherapy, magnetic resonance image
      studies revealed no evidence of the tumor. CONCLUSION: The second tumor was
      considered to be a metachronous neoplasm rather than a recurrence of the original
      mixed germ-cell tumor, which consisted a yolk-sac tumor and a germinoma.

PMID- 17187271
TI  - Dynamic morphological changes in lumbosacral lipoma during the first months of
      life revealed by constructive interference in steady-state (CISS) MR imaging.
AB  - OBJECTS AND METHODS: In this study, we demonstrate the morphological change in
      two cases of lumbosacral lipoma during the first few months of life using a three
      dimensional Fourier transformation-constructive interference in a steady-state
      (CISS) sequence that enables high-resolution images to be obtained with excellent
      contrast between cerebrospinal fluid (CSF), spinal roots, and lipoma. RESULTS:
      The CISS images clearly demonstrated the dynamic morphological changes such as
      lipoma growth observed in both cases and increased tethering effect in the case
      with lipomyelomeningocele. CONCLUSION: We have to keep in mind the potential for
      these morphological changes of the spinal lipoma during the first few months of
      life.

PMID- 17187272
TI  - HydroCoil embolization of a ruptured infectious aneurysm in a pediatric patient:
      case report and review of the literature.
AB  - INTRODUCTION: Intracranial infectious aneurysms in the pediatric population are
      rare. Although surgery has been the traditional treatment of ruptured pediatric
      infectious aneurysms, endovascular coil embolization has become an attractive
      alternative due to its low rate of morbidity and mortality. CASE REPORT: A 9-year
      old boy with a significant medical history of aortic valve replacement,
      antibiotic-treated infective endocarditis, and multiple embolic cerebral infarcts
      presented with a high-grade intraventricular hemorrhage due to the rupture of a
      large infectious proximal posterior circulation aneurysm. Computed tomography and
      cerebral angiogram demonstrated a right crural/ambient cistern hematoma and an
      associated infectious aneurysm of the right proximal posterior cerebral artery.
      The ruptured infectious aneurysm was coil-embolized with hydrogel-coated platinum
      coils without sacrifice of the distal parent artery. The aneurysm was completely
      occluded, and the patient regained all neurological function. CONCLUSION:
      Ruptured infectious aneurysms in the pediatric population occur despite
      aggressive medical therapy. Patients with infective endocarditis and embolic
      infarcts should be followed closely due to the risk of major hemorrhagic events,
      including aneurysm rupture. Hybrid coil embolization of ruptured infectious
      aneurysms with preservation of the distal parent artery is exceedingly rare and
      effective in the management of ruptured infectious aneurysms in the pediatric
      population.

PMID- 17187273
TI  - Medulloblastoma in a child with Duchenne muscular dystrophy.
AB  - MATERIALS AND METHODS: A 7-year-old boy diagnosed with Duchenne muscular
      dystrophy (DMD) presented with clinical features of raised intracranial tension.
      A CT scan revealed an enhancing vermian mass extending on to the fourth
      ventricle, which was excised and reported to be medulloblastoma. The patient was
      treated with craniospinal radiotherapy but progressed after 6 months. DISCUSSION:
      Neoplasms associated with DMD are rare and the present case may well be the first
      one with medulloblastoma. Interestingly, all neoplasms associated with DMD
      reported so far have been round cell tumors, which may lead to insights into
      their possible molecular associations.

PMID- 17187268
TI  - Portrait of multifaceted transporter, the multidrug resistance-associated protein
      1 (MRP1/ABCC1).
AB  - MRP1 (ABCC1) is a peculiar member of the ABC transporter superfamily for several
      aspects. This protein has an unusually broad substrate specificity and is capable
      of transporting not only a wide variety of neutral hydrophobic compounds, like
      the MDR1/P-glycoprotein, but also facilitating the extrusion of numerous
      glutathione, glucuronate, and sulfate conjugates. The transport mechanism of MRP1
      is also complex; a composite substrate-binding site permits both cooperativity
      and competition between various substrates. This versatility and the ubiquitous
      tissue distribution make this transporter suitable for contributing to various
      physiological functions, including defense against xenobiotics and endogenous
      toxic metabolites, leukotriene-mediated inflammatory responses, as well as
      protection from the toxic effect of oxidative stress. In this paper, we give an
      overview of the considerable amount of knowledge which has accumulated since the
      discovery of MRP1 in 1992. We place special emphasis on the structural features
      essential for function, our recent understanding of the transport mechanism, and
      the numerous assignments of this transporter.

PMID- 17187274
TI  - Intra-articular hyaluronic acid after knee arthroscopy: a two-year study.
AB  - Arthroscopic knee joint lavage is used when conservative treatment of knee
      osteoarthritis is unsatisfactory and a joint prosthesis is not yet indicated. The
      potentially negative effect of irrigation fluids on cartilage metabolism and
      structure has led to the development of a temporary synovial fluid substitute
      containing hyaluronic acid. The short and long-term effects of this synovial
      fluid substitute were investigated in a total of 80 patients with persistent knee
      pain. Forty patients underwent arthroscopic knee joint lavage, in some cases
      combined with careful cartilage debridement (group A) while a further 40 patients
      underwent the same procedure which, after final joint lavage, was immediately
      followed by a single instillation of 10 ml of the synovial fluid substitute (0.5%
      sodium hyaluronate) into the joint (A + HA group). After the procedure, pain on
      walking and restricted ability to walk 100 m were markedly reduced to a
      comparable extent in both groups. Three months later, the effect of the treatment
      assessed using various parameters (CGI, restricted ability to walk 100 m, pain on
      walking, night pain) had decreased in group A, while it remained stable or even
      improved slightly in the A + HA group. The Mann-Whitney statistics revealed a
      descriptive superiority for the A + HA group at this time point. One year after
      treatment the superiority of the A + HA group was confirmed using the same
      assessment parameters. No side effects or adverse events were observed for either
      treatment procedure. This study shows that arthroscopic knee joint lavage leads
      to a lasting improvement in pain and functional impairment. The post-arthroscopic
      instillation of a HA-based synovial fluid substitute into the joint is a suitable
      way of achieving long-term stabilisation of the treatment outcome. This was
      supported by findings of a survey of 66 patients at 2 years after treatment in
      this study. Level I prospective, randomised controlled double-blind study.

PMID- 17187275
TI  - Reconstruction of the superior peroneal retinaculum using an autologous gracilis
      tendon graft for chronic dislocation of the peroneal tendons accompanied by
      lateral instability of the ankle: technical note.
AB  - This is a technical note on reconstructive surgery for the combination of chronic
      dislocation of the peroneal tendons and lateral instability of the ankle. The
      traditional surgery for this condition consists of direct repairs of the lateral
      ligaments of the ankle and the superior peroneal retinaculum, if possible.
      However, repair surgery is difficult in cases with insufficient structural
      remnants. We describe here a technique of simultaneous reconstruction of the
      anterior talofibular ligament and superior peroneal retinaculum with an
      autologous gracilis tendon graft for the combination of chronic dislocation of
      the peroneal tendons and lateral instability of the ankle.

PMID- 17187276
TI  - A glass foreign body in the knee joint mistaken for ACL avulsion: an unusual
      case.
AB  - Foreign body in the knee is associated with trauma to knee or deliberate self
      harm. We see them often in clinical practice. They come in all forms and shapes.
      Very rarely one can find a foreign body within a joint without obvious external
      scarring (e.g. needle). We have not come across anywhere in the literature of a
      large foreign body in the knee joint without a definitive history of injury where
      the external scar has healed so well to become inconspicuous. With this
      background it is even more difficult when the X-rays mimic anterior cruciate
      ligament (ACL) avulsion. This case report highlights the fact that diagnosis of a
      foreign body in the knee joint can sometimes be challenging and almost impossible
      when there is no history of any injury and when the X-ray mimics ACL avulsion.

PMID- 17187277
TI  - Anterior medial meniscus detachment and anterior cruciate ligament tear.
AB  - This paper reports on two cases of medial meniscus injury involving detachment of
      the anterior horn together with a coronary ligament tear. Both cases were
      associated with tearing of the anterior cruciate ligament. The meniscal injuries
      observed were similar to those reported in the literature prior to the
      development of arthroscopic surgery. Variant attachments of the anterior horn of
      the medial meniscus are thought to have contributed to this injury.

PMID- 17187278
TI  - Late spontaneous haemarthrosis: an unusual complication following an
      unicompartmental knee arthroplasty.
AB  - A man, aged 55, presented with a spontaneous haemarthrosis of his right knee, 1
      year after an unicompartmental knee replacement. This case showed an atraumatic
      rupture of the metal marker wire of an all-polyethylene inlay tibial implant
      which caused a destruction of the polyethylene surface and a disseminated
      synovitis of the right knee. This is a rare but destructive complication
      following an unicompartmental knee arthroplasty.

PMID- 17187279
TI  - Arthroscopic treatment for synovial chondromatosis of the subacromial bursa: a
      case report.
AB  - Synovial chondromatosis of the subacromial bursa has been reported rarely. To the
      best of our knowledge, there was no case report of arthroscopic treatment for
      synovial chondromatosis of the subacromial bursa in English literature. The
      authors present a case of synovial chondromatosis of the subacromial space in a
      45-year-old male, which was managed by arthroscopy. This rare condition can be
      well managed on similar lines as the other joints through arthroscopic surgery.

PMID- 17187280
TI  - The effect of graft tensioning in anatomic 2-bundle ACL reconstruction on knee
      joint kinematics.
AB  - Recently, double bundle ACL reconstruction, in which the two bundles thought to
      have different effects on knee kinematics are reconstructed separately, is widely
      believed to more favorably restore normal knee kinematics than conventional
      single bundle ACL reconstruction. However, rotational kinematics during
      physiological movement after double bundle reconstruction has rarely been tested.
      The purpose of this study was to measure the kinematics of the ACL deficient and
      reconstructed knees using two different tensioning conditions in double bundle
      reconstruction, and to examine the effects of each graft on knee kinematics. Six
      cadaveric knees were used. Six degrees-of-freedom of knee kinematics and the
      tension of each graft were monitored during simulated knee extension with the ACL
      intact, resected, and reconstructed under two different tensioning conditions: 50
      N on anteromedial bundle and 0 N on posterolateral bundle (AM-favored condition);
      0 N on anteromedial bundle and 50 N on posterolateral bundle (PL-favored
      condition). Tibial translation: After ACL reconstruction, the tibia overcorrected
      posteriorly in both conditions. Such an overcorrection in the AM-favored
      condition was larger than in the PL-favored condition. Tibial rotation: The tibia
      was significantly externally rotated after ACL reconstruction at a low flexion
      angle in both conditions. However, at a high flexion angle, tibial external
      rotation was shown only in the AM-favored condition. Graft tension: While total
      tensions were similar between the two conditions, the AM bundle shared more
      tension in the AM-favored condition than in the PL-favored condition. A total of
      50 N of tension force was assumed to be excessive for normalizing knee kinematics
      at a low flexion angle even if double bundle reconstruction was used.
      Additionally, the AM-favored tensioning reconstruction made the tibia rotate
      externally and translate posteriorly even at a high flexion angle. Further
      research is needed to normalize knee kinematics after ACL reconstruction, however
      it is recommended that a moderate tensioning force is applied to the PL bundle
      and a minimal tensioning force to the AM bundle in double bundle reconstruction
      to obtain better knee kinematics.

PMID- 17187281
TI  - Effects of hyperbaric oxygen on gene expressions of procollagen, matrix
      metalloproteinase and tissue inhibitor of metalloproteinase in injured medial
      collateral ligament and anterior cruciate ligament.
AB  - Animal experiments were performed to investigate whether and how the
      administration of hyperbaric oxygen (HBO) affects gene expressions of
      procollagens, matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs) in injured medial collateral ligament (MCL) and
      anterior cruciate ligament (ACL). In 64 Sprague-Dawley rats, the MCL of the left
      knee was lacerated at the midsubstance, and the ACL of the left knee was
      lacerated adjacent to the tibial insertion in another 64 rats. Of these, 32 rats
      with lacerated MCL and 32 rats with lacerated ACL were housed in individual cages
      at normal atmospheric pressure (Groups MC and AC, respectively), while the
      remaining 64 rats were exposed to 100% oxygen at 2.5 atmospheres absolute for 2 h
      for 5 days a week (Groups MH and AH, respectively). Rats were sacrificed at 3, 7,
      14 and 28 days postoperatively. After macroscopic examination, bilateral MCLs
      were harvested from Groups MC and MH, and bilateral ACLs from Groups AC and AH.
      Total RNA was extracted from each specimen and gene expressions of type I and
      type III procollagens, MMP-2, -9 and -3, and TIMP-1 and -2 were estimated using
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).
      Macroscopically, lacerated MCL healed by scar tissue formation, the amount of
      which appeared to be greater in Group MH than in Group MC. In contrast, no
      lacerated ACLs united, and little, if any, differences were apparent in
      macroscopic findings between Groups AH and AC. Gene expression of type I
      procollagen was significantly greater in Group MH than in Group MC at 7 days
      postoperatively and was also significantly greater in Group AH than in Group AC
      at 28 days (P<0.05). No significant differences in type III procollagen gene
      expression were noted between Groups MH and MC or between Groups AH and AC. In
      addition, no significant differences in gene expressions of MMPs were seen in
      either ligament, except that gene expression of MMP-13 was significantly lower at
      7 days in Group MH than in Group MC (P<0.05). Gene expressions of TIMPs did not
      differ significantly between Groups MH and MC in each time interval, whereas gene
      expressions of TIMPs were significantly greater in Group AH than in Group AC at
      7, 14 and 28 days for TIMP-1 and at 3, 7 and 14 days for TIMP-2 (P<0.05). RT-PCR
      results suggested that HBO enhances structural protein synthesis and inhibits
      degradative processes by enhancing TIMP activities in the lacerated ACL. However,
      none of the lacerated ACLs united macroscopically despite administration of HBO,
      indicating that the effect of HBO is insufficient for healing of the injured ACL.
      If HBO therapy is used as an adjunctive therapy after primary repair of the
      injured ACL, the success rate of surgery seems likely to be increased.

PMID- 17187282
TI  - Stabilizing effect of the transferred conjoined tendon on shoulder stability.
AB  - The modified Boytchev procedure, i.e., rerouting of the coracoid process with its
      attached conjoined tendon (short head of biceps and coracobrachialis) deep to the
      subscapularis and reattachment to its anatomical location, has been advocated for
      recurrent anterior glenohumeral instability with controversial clinical outcomes.
      We aimed to investigate the dynamic contribution of the conjoined tendon in situ
      or transferred to the glenohumeral articulation in stable and unstable shoulders.
      Eight cadaveric shoulders were tested with the arm in 90 degrees abduction and 90
      degrees external rotation. A constant 1.5 kg anterior translation force was
      applied to the proximal humerus, combined with 0, 1.5, 3.0 kg of load applied to
      the conjoined tendon sequentially. Anterior displacement of the humeral head
      relative to the scapula was recorded before and after an imitation Bankart lesion
      was created, and after treated with the modified Boytchev procedure for the
      Bankart lesion. Application of load to the conjoined tendon significantly reduced
      anterior displacement of the humeral head either with the capsule intact or with
      Bankart lesion simulated. The most significant decrease of the anterior
      displacement occurred when the conjoined tendon was transferred beneath the
      subscapularis. Our findings show that the conjoined tendon per se has a
      stabilizing effect on stable and unstable shoulders and therefore provide
      scientific support for the treatment of recurrent shoulder instability using the
      modified Boytchev procedure.

PMID- 17187284
TI  - Non-standard PET radionuclides: time to get ready for new clinical PET
      strategies.

PMID- 17187283
TI  - Reproductive hormone effects on strength of the rat anterior cruciate ligament.
AB  - The material properties of the anterior cruciate ligament (ACL) in female rats
      with normal estrous cycles were compared to those regulated by oral contraceptive
      steroids. Forty female Sprague-Dawley rats were divided into two groups: an
      experimental group received daily ethinylestradiol and levonorgestrel in a dosing
      model designed to simulate a typical oral contraception regime in humans, while a
      control group received daily oral placebo. After eight cycles, six rats from each
      group underwent daily phlebotomy to measure serum estradiol and progesterone
      levels over the course of a single 5-day estrous cycle. Significant differences
      between groups were found for the area under the curve of blood progesterone
      levels versus time over the length of the estrous cycle (P=0.02). After 12
      cycles, the rats were euthanized and one femur-ACL-tibia complex from each animal
      was dynamically loaded to failure. The ACLs from the rats in the experimental
      group had significantly decreased average and tangent stiffness, (P=0.002 and
      0.0001, respectively), and significantly increased elongation (P=0.002) and total
      energy absorbed (P=0.03), or greater toughness than controls. In rats, it appears
      that the administration of reproductive hormones designed to simulate typical
      oral contraception in humans alters the mechanical properties of the rat ACL.

PMID- 17187285
TI  - Adrenalectomy for metastases from hepatocellular carcinoma - a single center
      experience.
AB  - BACKGROUND: Adrenal metastases (AM) from hepatocellular carcinoma (HCC) are
      rarely seen in clinical practice. The treatment is not standardized, the
      indications and efficacy of different therapeutic approaches being still
      controversial. PATIENTS: Between January 1995 and December 2005, 174 patients
      underwent liver resection for HCC in our center. AM were detected in four
      patients (2.3%): three of them had HCC and synchronous AM, and the remaining one
      developed AM 10 months after liver resection. All the patients with AM were
      treated by adrenalectomy (simultaneously with liver resection in synchronous
      metastases), followed by systemic chemotherapy. Non-resectable multifocal liver
      recurrences occurred in two patients, one of them having also a contralateral
      adrenal metastasis; these two patients are presently alive 26 and 43 months after
      adrenalectomy, respectively. Another patient died by liver recurrence 27 months
      postoperatively. The fourth patient is disease-free at 17 months after the
      initial operation. CONCLUSIONS: Adrenalectomy for AM from HCC should be performed
      whenever the primary tumor is well therapeutically controlled and the patient has
      a good performance status. Adrenalectomy offers the chance of more than 2 years
      survival in many patients. However, once AM are detected, the prognosis remains
      poor.

PMID- 17187286
TI  - PTH spikes during parathyroid exploration--a possible pitfall during PTH
      monitoring?
AB  - BACKGROUND AND AIMS: Parathyroid hormone (PTH) spikes caused by unintentional
      manipulation of the hypersecreting glands may lead to interpretation problems in
      intraoperative PTH monitoring. Their frequency and surgical consequences were
      evaluated. MATERIALS AND METHODS: Intraoperative PTH values of 401 patients with
      primary hyperparathyroidism and single gland disease were analysed. Patients were
      divided into four groups: extensive increase (>150 pg/ml), moderate PTH increase
      (<150 pg/ml), no increase (+/-50 pg/ml) and decrease before excision as referred
      to the baseline level before skin incision. PTH was measured before and up to 25
      min after removal of the enlarged gland. RESULTS: Twenty-two (5.5%) patients had
      an extensive and 36 (9%) a moderate intraoperative PTH increase. The PTH decline
      was prolonged to 15 min in 7 (31.8%) and to 25 min in 12 (54.5%) patients after
      extensive manipulation and in 9 patients (25%) each after moderate manipulation,
      respectively. No increase occurred in 162 (40.4%) and a decrease in 181 (45.1%)
      patients. The surgical approach (bilateral exploration vs open, minimally
      invasive parathyroidectomy) did not show a difference in the rate of PTH spikes.
      CONCLUSION: PTH spikes often cause a prolonged PTH decline but, when recognized,
      do not lead to a change in the surgical strategy.

PMID- 17187287
TI  - CCM1 gene deletion identified by MLPA in cerebral cavernous malformation.
AB  - Familial cerebral cavernous malformations (CCMs) occur with a frequency of 1 in
      2000 and may cause recurrent headaches, seizures, and hemorrhagic stroke. Exon
      scanning-based methods have identified intragenic mutations in three genes, CCM1,
      CCM2, and CCM3, in about 70% of familial CCM. To date, only two large CCM2 and a
      single large CCM3 deletion have been published. In addition to direct sequencing
      of all three CCM genes, we applied a newly developed multiplex ligation-dependent
      probe amplification gene dosage assay (MLPA) designed to detect genomic CCM1-3
      deletions/duplications. Direct sequencing did not reveal a mutation in the index
      case who presented with multiple CCMs that had caused a generalized tonic-clonic
      seizure with Todd's paralysis and headaches at the age of 5. In contrast, MLPA
      analyses detected a large deletion involving the entire CCM1 coding region in the
      proband and further affected members of this German CCM family. The MLPA results
      were corroborated by analyses of single nucleotide polymorphisms (SNPs) within
      the CCM1 gene. Thus, we here present the first report on a CCM1 gene deletion.
      Our results confirm a loss-of-function mutation mechanism for CCM1 and
      demonstrate that the use of MLPA enables a higher CCM mutation detection rate
      which is crucial for predictive testing of at-risk relatives.

PMID- 17187288
TI  - Unusual distribution of red marrow mimicking chloroma in a patient with acute
      myelogenous leukemia.
AB  - We present a case of unusual distribution of red marrow in a patient with
      extramedullary acute myelogenous leukemia (AML). In adults, hematopoietic marrow
      is usually located in the axial skeleton and the proximal aspects of the limbs,
      except for the epiphyses. Nodular islets of red marrow located in the epiphyseal
      and distal parts of the limbs may mimic tumoral infiltration and be mistaken for
      chloroma in a patient with AML.

PMID- 17187289
TI  - Use of gadolinium chelate to confirm epidural needle placement in patients with
      an iodinated contrast reaction.
AB  - OBJECTIVE: When performing epidural steroid injections for the management of
      chronic back pain, imaging guidance and a limited epidurogram improve accuracy of
      needle placement and ensure appropriate delivery of the injectate into the
      epidural space. We describe our experience using a gadolinium chelate as an
      alternative contrast agent for limited epidurography in patients with a history
      of an iodinated contrast reaction. DESIGN: Thirty-eight of 2,067 (1.8%) epidural
      steroid injections performed in our department over a 25-month period (December
      2003-January 2006) employed gadolinium. All injections were performed in the
      lumbar spine employing a paramedian interlaminar approach. Procedural notes and
      patient charts were reviewed to evaluate for immediate or delayed complications
      related to incorrect intrathecal or intravascular needle placement. A
      retrospective analysis of selected fluoroscopic spot images was performed to
      evaluate confidence of epidural needle placement; this analysis compared these
      spot images against those obtained from age- and gender-matched control patients
      in whom iodinated contrast was used to confirm needle placement. RESULTS: Real
      time fluoroscopic guidance permitted confident visualization of an epidurogram at
      the time of procedure in all 38 cases as documented in the procedural report, and
      no procedure resulted in a complication due to incorrect needle placement.
      Retrospective review of fluoroscopic spot images revealed at least moderate
      confidence of epidural needle placement by both readers in 29/38 cases (76.3%).
      Fluoroscopic spot images obtained using gadolinium yielded significantly less
      confidence than images obtained in control patients whose procedures were
      performed using iodinated contrast (P < 0.01). However, operators were
      sufficiently confident in needle placement based on real-time fluoroscopic images
      (not available in our subsequent review) to inject anesthestic in all 38 cases,
      despite the immediate consequences that could result from intrathecal
      administration. During the same time period, there were 11/2,067 (0.5%) instances
      of intrathecal needle placement discovered during attempted epidurography despite
      the use of fluoroscopy for needle guidance and reliance on loss-of-resistance
      technique. CONCLUSION: Gadolinium chelate represents a safe and useful
      alternative contrast agent for confirmation of epidural needle placement in
      patients with an iodinated contrast allergy.

PMID- 17187290
TI  - The clinico-anatomic explanation for tibial intraneural ganglion cysts arising
      from the superior tibiofibular joint.
AB  - OBJECTIVE: To demonstrate that tibial intraneural ganglia in the popliteal fossa
      are derived from the posterior portion of the superior tibiofibular joint, in a
      mechanism similar to that of peroneal intraneural ganglia, which have recently
      been shown to arise from the anterior portion of the same joint. DESIGN:
      Retrospective clinical study and prospective anatomic study. MATERIALS: The
      clinical records and MRI findings of three patients with tibial intraneural
      ganglion cysts were analyzed and compared with those of one patient with a tibial
      extraneural ganglion cyst and one volunteer. Seven cadaveric limbs were dissected
      to define the articular anatomy of the posterior aspect of the superior
      tibiofibular joint. RESULTS: The condition of the three patients with intraneural
      ganglia recurred because their joint connections were not identified initially.
      In two patients there was no cyst recurrence when the joint connection was
      treated at revision surgery; the third patient did not wish to undergo additional
      surgery. The one patient with an extraneural ganglion had the joint connection
      identified at initial assessment and had successful surgery addressing the cyst
      and the joint connection. Retrospective evaluation of the tibial intraneural
      ganglion cysts revealed stereotypic features, which allowed their accurate
      diagnosis and distinction from extraneural cases. The intraneural cysts had
      tubular (rather than globular) appearances. They derived from the postero
      inferior portion of the superior tibiofibular joint and followed the expected
      course of the articular branch on the posterior surface of the popliteus muscle.
      The cysts then extended intra-epineurially into the parent tibial nerves, where
      they contained displaced nerve fascicles. The extraneural cyst extrinsically
      compressed the tibial nerve but did not directly involve it. All cadaveric
      specimens demonstrated a small single articular branch, which derived from the
      tibial nerve to the popliteus. The branch coursed obliquely across the posterior
      surface of the popliteus muscle before innervating the postero-inferior aspect of
      the superior tibiofibular joint. CONCLUSIONS: The clinical, MRI and anatomic
      features of tibial intraneural ganglion cysts are the posterior counterpart of
      the peroneal intraneural ganglion cysts arising from the anterior portion of the
      superior tibiofibular joint. These predictable features can be exploited and have
      implications for the pathogenesis of these intraneural cysts and treatment
      outcomes. These ganglion cysts are joint-related and provide further evidence to
      support the unifying articular theory. In each case the joint connection needs to
      be identified preoperatively, and the articular branches and the superior
      tibiofibular joint should be addressed operatively to prevent cyst recurrence.

PMID- 17187292
TI  - Siegesbeckia yellow vein virus is a distinct begomovirus associated with a
      satellite DNA molecule.
AB  - Leaf samples of Siegesbeckia glabrescens showing yellow vein, enation, and
      stunting symptoms were collected in Guangdong province, China. A specific 500-bp
      product was consistently detected in total DNA extracts, amplified with universal
      primers specific for members of the genus Begomovirus. Comparison of partial DNA
      sequences revealed that these virus isolates were identical, and therefore
      isolates GD13, GD24 and GD27 were selected for further sequence analysis. The
      complete nucleotide sequences of GD13, GD24 and GD27 were all found to be 2768
      nucleotides (nts) long, with two open reading frames (ORFs) in the virion-sense
      strand and four ORFs in the complementary-sense strand, typical of the Old World
      begomoviruses. Sequence identities among the three isolates ranged from 99.7 to
      99.8%. When compared with other reported sequences of begomoviruses, GD13 was
      most closely related to papaya leaf curl China virus (AJ876548), with a sequence
      identity of 76.8%. In addition, all isolates were found to be associated with
      DNAbeta molecules. The complete DNAbeta sequences of isolates GD13, GD24 and GD27
      were determined. Sequence analysis showed that they had highest sequence identity
      with DNAbeta of Eupatorium yellow vein virus (AJ438938) (44.0, 43.9 and 45.6%
      identity). GD13, GD24 and GD27 are considered to be isolates of a distinct
      begomovirus species for which the name Siegesbeckia yellow vein virus (SgYVV) is
      proposed.

PMID- 17187291
TI  - Growth hormone response in low-dose apomorphine test correlates with
      nigrostriatal dopamine transporter binding in patients with Parkinson's disease.
AB  - Challenge with low-dose apomorphine causes a rise in growth hormone (GH) in
      patients with Parkinson's disease (PD). We studied 18 patients with early PD, who
      showed an increase of GH in the low-dose apomorphine test, by means of [(123)I]
      FP-CIT-SPECT. The mean specific dopamine transporter binding of the 18 patients
      was 1.50 +/- 0.56 in the striatum, 1.20 +/- 0.59 in the putamen, and 1.76 +/-
      0.59 in the caudate nucleus. The increase of GH (1.05 +/- 1.01 ng/ml at baseline
      to 9.46 +/- 6.36 ng/ml 45 min after apomorphine injection; p < 0.001) was
      significant. There was a significant negative correlation of the increase of GH
      with the mean specific dopamine transporter binding in all three regions (r
      between -0.490 and -0.587; p between 0.04 and 0.01). Challenge with low-dose
      apomorphine may therefore be used as an indirect tool to measure the extent of
      nigrostriatal neurodegeneration in early PD.

PMID- 17187293
TI  - Complete nucleotide sequences of Malvastrum yellow mosaic virus and its
      associated DNA beta molecule.

PMID- 17187295
TI  - Sequence analysis of the entire RNA genome of a sweet potato chlorotic fleck
      virus isolate reveals that it belongs to a distinct carlavirus species.
AB  - Since the paucity of information on sweet potato chlorotic fleck virus (SPCFV)
      had precluded its classification, we have determined the complete nucleotide
      sequence of the single-stranded RNA genome of a Ugandan isolate of SPCFV. The
      genome is 9104 nucleotides long (excluding the poly(A) tail) and potentially
      includes six open reading frames (ORFs). Based on genomic organisation and
      sequence similarity, SPCFV appears to be a member of the genus Carlavirus (family
      Flexiviridae). However, SPCFV is distantly related to typical carlaviruses, as
      most of its putative gene products share amino acid sequence identities of <40%
      with those of typical carlaviruses. Its closest relative is melon yellowing
      associated virus, a proposed carlavirus from Brazil, with which it shares ORF5
      and ORF6 amino acid sequence identities of 61 and 46%, respectively.

PMID- 17187294
TI  - Comparison of SAT-1 foot-and-mouth disease virus isolates obtained from East
      Africa between 1971 and 2000 with viruses from the rest of sub-Saharan Africa.
AB  - Foot-and-mouth disease serotype SAT-1 seems to be endemic in many sub-Saharan
      African countries. Phylogenetic analysis using the 1D gene of 51 SAT-1 isolates
      from East, West and southern Africa indicated the presence of at least 6 lineages
      and 11 genotypes with linkages between various geographical regions of the
      subcontinent. Differences were observed between countries in East Africa, the
      main focus of this study, with individual countries suffering outbreaks from
      isolates belonging to various genotypes, which is evidence of reintroduction of
      strains and long-term circulation of outbreak viruses. The amount of variation
      observed has significant implications for disease control on the subcontinent.

PMID- 17187296
TI  - Mapping the 5' ends of banana bunchy top virus gene transcripts.
AB  - Banana bunchy top virus (BBTV), a multi-component circular ssDNA virus,
      replicates via a dsDNA intermediate that also serves as a template for virion
      sense transcription. Seven virus-derived transcripts have been previously
      identified and analysed in BBTV-infected bananas by northern analysis and 3'
      rapid amplification of cDNA ends (3' RACE). In this study, we have used RNA
      ligase-mediated rapid amplification of 5' cDNA ends (RLM-RACE) to complete the
      mapping of the BBTV gene transcripts and have now fully mapped the transcribed
      regions of each BBTV component and effectively defined the upstream regulatory
      region.

PMID- 17187297
TI  - Effect of anthocyanin-rich extract from black rice (Oryza sativa L. indica) on
      hyperlipidemia and insulin resistance in fructose-fed rats.
AB  - This study was designed to evaluate the effect of an anthocyanin-rich extract
      from black rice on hyperlipidemia and insulin resistance in fructose-fed rats.
      Rats fed fructose diet for 4 weeks exhibited significantly higher plasma insulin
      levels and lower insulin sensitivity than the control rats fed AIN-93G diet.
      Dietary supplementation with the anthocyanin-rich extract (5 g/kg of high
      fructose diet) prevented the development of fructose-induced insulin resistance.
      After fructose-induced insulin resistance had been established, 4-week treatment
      with the anthocyanin-rich extract (5 g/kg of high-fructose diet) or pioglitazone
      (270 mg/kg of high-fructose diet) ameliorated the glucose intolerance and
      hyperlipidemia, but the extract failed to reverse the fructose-induced
      hyperinsulinemia as pioglitazone did. In addition, rats supplemented by the
      extract exhibited lower oxidative stress than the fructose-fed controls, as
      indicated by the lower concentrations of plasma thiobarbituric acid reactive
      substances and blood oxidized glutathione. Overall, these results suggest that
      the anthocyanin-rich extract from black rice improves certain metabolic
      abnormalities associated with diets high in fructose.

PMID- 17187299
TI  - Solitary foraging in the ancestral South American ant, Pogonomyrmex vermiculatus.
      Is it due to constraints in the production or perception of trail pheromones?
AB  - Several North American species of Pogonomyrmex harvester ants exhibit group
      foraging, whereas South American species are exclusively solitary foragers. The
      composition of the secretions of the poison and Dufour glands in the South
      American species, Pogonomyrmex vermiculatus, were analyzed, and the secretions
      and their components were tested as trail pheromones in laboratory bioassays. The
      major compounds in the poison gland were the alkylpyrazines, 2,5
      dimethylpyrazine, 2,3,5-trimethylpyrazine, and 3-ethyl-2,5-dimethylpyrazine. The
      Dufour gland contained five alkanes, from tridecane to heptadecane, with
      pentadecane being most abundant. In behavioral bioassays, poison gland extracts
      and the mixture of pyrazines produced a trail pheromone effect, whereas the
      Dufour gland extracts and the alkanes had no effect on ant locomotion. We
      conclude that group foraging in P. vermiculatus does not arise from the inability
      to produce or detect possible pheromones, but rather, from physiological and/or
      ecological factors.

PMID- 17187298
TI  - Transition age youth in publicly funded systems: identifying high-risk youth for
      policy planning and improved service delivery.
AB  - Youth with Serious Emotional Disturbances (SED) face many challenges as they
      approach the transition to adulthood and adult services. This study examines
      publicly funded transition-age youth in order to describe the numbers and type of
      youth in need of policy and service planning in one state. Using Medicaid
      enrollment and claims/encounter data, youth with high risk of transition
      difficulties were identified in the following groups: SED, state custody/foster
      care or risk of custody, users of intensive or frequent mental health services,
      or having diagnoses of major mental disorders, conduct disorders, or
      developmental disabilities. Almost one quarter of all enrolled 14 to 17-year olds
      met criteria for at least one of the high risk groups, and three-quarters of
      these were youth with SED. High risk youth are described, with greater detail on
      those with SED, and implications for policy, services, and research are
      discussed.

PMID- 17187300
TI  - A uniaxial bioMEMS device for quantitative force-displacement measurements.
AB  - There is a need for experimental techniques that allow the simultaneous imaging
      of cellular cystoskeletal components with quantitative force measurements on
      single cells. A bioMEMS device has been developed for the application of strain
      to a single cell while simultaneously quantifying its force response. The
      prototype device presented here allows the mechanical study of a single, adherent
      cell in vitro. The device works in a fashion similar to a displacement-controlled
      uniaxial tensile machine. The device is calibrated using an AFM cantilever and
      shows excellent agreement with the calculated spring constant. The device is
      demonstrated on a single fibroblast. The force response of the cell is seen to be
      linear until the onset of de-adhesion with the de-adhesion from the cell platform
      occurring at a force of approximately 1500 nN.

PMID- 17187301
TI  - EORTC-NCI-AACR - 18th Symposium - Molecular Targets and Cancer Therapeutics.

PMID- 17187302
TI  - EORTC-NCI-AACR - 18th Symposium - Molecular Targets and Cancer Therapeutics.
      Updates on cancer drugs.

PMID- 17187303
TI  - EORTC-NCI-AACR - 18th Symposium - Molecular Targets and Cancer Therapeutics.
      Pediatric drugs, biomarkers and new therapies.

PMID- 17187304
TI  - EORTC-NCI-AACR - 18th Symposium - Molecular Targets and Cancer Therapeutics. New
      approaches in treating cancer.

PMID- 17187305
TI  - American Heart Association - Scientific Sessions 2006.

PMID- 17187306
TI  - American Heart Association - Scientific Sessions 2006. Developments in
      cardiovascular-related therapies.

PMID- 17187308
TI  - Frontiers in Cancer Prevention Research - Fifth Annual AACR Conference.

PMID- 17187307
TI  - American Heart Association - Scientific Sessions 2006. Cell therapies for
      ischemic tissues and treatments for lipid metabolism disorders.

PMID- 17187309
TI  - Clinical Trials in CNS - SMi conference.

PMID- 17187310
TI  - The second annual Burrill personalized medicine conference.

PMID- 17187311
TI  - Discovery on Target 2006 - CHI's fourth annual event. Chemogenomics: small
      molecules as biological probes.

PMID- 17187312
TI  - Infocast End to End Preparedness for Pandemic Influenza. Opportunities for public
      private collaboration.

PMID- 17187313
TI  - New ocular therapeutics: a view from the patenting perspective.
AB  - This feature article provides an overview of the newest therapeutic developments
      for ocular diseases, based on patents and patent applications that were published
      in the 12-month period from November 2005 to October 2006. In contrast to peer
      reviewed literature covering breakthroughs in basic science research, the
      patenting perspective discloses the intentions of the pharmaceutical industry for
      imminent drug development. Selected documents describing drug delivery, dry eye
      syndrome, ocular infections and lesions, glaucoma and age-related macular
      degeneration are discussed. The role of RNA interference, which is of particular
      interest in ophthalmology research, is also highlighted.

PMID- 17187314
TI  - The development of chalcones as promising anticancer agents.
AB  - Chalcones are polyketide natural products that display various biological
      activities, including anticancer properties. Compelling data from laboratory
      studies indicate that chalcones have important effects on cancer cell growth and
      proliferation. Many mechanisms of action have been identified, including the
      inhibition of tubulin assembly, inhibition of angiogenesis, induction of
      apoptosis, anti-estrogenic activity and reversal of multidrug resistance - or a
      combination of these mechanisms. Based on these results, chalcones appear to be
      promising anticancer agents.

PMID- 17187315
TI  - Drug interactions: concerns and current approaches.
AB  - Following the recent withdrawal of several prominent drugs from US and European
      markets because of detrimental drug-drug interactions, metabolic drug
      interactions have received considerable attention in the pharmaceutical industry.
      In turn, the question of drug safety has received significant legal, regulatory
      and commercial emphasis, bringing this issue to the forefront of both industry
      and government drug agendas. The value of predicting the drug interactions of
      compounds as early as possible in the drug discovery process for all therapeutic
      areas cannot be underestimated. From 1964 to 1999, approximately 8% of the drugs
      approved by the FDA were later withdrawn from the US market. Pharmaceutical
      companies are facing increasing pressure to prove the long-term safety of their
      products, and this is complicated by the fact that animal models are not
      perfectly predictive of human responses, and may provide contradictory
      information. The failure to address safety concerns successfully during the drug
      optimization process may result in companies withdrawing any approved drugs from
      the market; drug safety issues not only present human health consequences, but
      also have a negative economic and public relations impact on the pharmaceutical
      industry. This paper discusses the significance of drug interactions, and
      addresses strategies to evaluate the potential of a drug candidate for drug
      interactions.

PMID- 17187316
TI  - Drug evaluation: apilimod, an oral IL-12/IL-23 inhibitor for the treatment of
      autoimmune diseases and common variable immunodeficiency.
AB  - Apilimod is a small molecule that inhibits IL-12 and IL-23 production - cytokines
      that are involved in autoimmune diseases - through the prevention of nuclear
      translocation of c-Rel. Synta Pharmaceuticals Corp is developing apilimod for the
      potential treatment of Crohn's disease (CD) and other autoimmune diseases.
      Preclinical studies demonstrated the successful inhibition of IL-12 and IL-23
      production by the drug. In the clinical setting, apilimod has been generally well
      tolerated, with mild-to-moderate side effects reported, including headaches and
      nausea. Patients with CD responded within 14 days of treatment with apilimod and,
      after 28 days, the drug significantly reduced the Crohn's disease activity index
      (CDAI). Apilimod is currently in phase II clinical trials for rheumatoid
      arthritis, common variable immunodeficiency and CD. From the data available to
      date, apilimod appears to be a promising treatment for CD, and the oral
      formulation of this compound provides an advantage for apilimod over injectable
      therapies.

PMID- 17187318
TI  - [Thrombosis of the inferior vena cava and the iliac and femoral veins in a 24
      year old man].
AB  - HISTORY AND ADMISSION FINDINGS: A 24-year-old patient presented with nonspecific
      epigastric pain, general feebleness and weakness of both legs. The
      cardiopulmonary investigations were unremarkable. The abdomen was soft, without
      muscular resistance or local pressure tenderness. Both legs were moderately
      swollen without other findings. INVESTIGATIONS: The laboratory tests showed an
      elevated D-dimer and fibrinogen, as well as a heterozygous factor V Leiden
      mutation. Both duplex ultrasonography and computed tomography revealed thrombosis
      of the distal inferior vena cava (IVC) and both iliac and femoral veins. A short
      segment of the IVC between the left renal and intrahepatic veins was a-genetic.
      DIAGNOSIS, TREATMENT AND COURSE: Anticoagulation treatment with phenprocoumon was
      started for the deep vein thrombosis. At the one-year follow-up no thrombosis of
      the vena cava and the iliac and femoral veins was detected. CONCLUSION:
      Thrombosis of the IVC in combination with a pelvic vein thrombosis is a rare
      condition in young patients. If this venous abnormality is found, thrombophilia
      should be considered in the differential diagnosis. Anticoagulation is the
      treatment of choice.

PMID- 17187317
TI  - [Metabolic syndrome and peripheral arterial occlusive disease as indicators for
      increased cardiovascular risk].
AB  - BACKGROUND AND AIMS: The usefulness of the metabolic syndrome (MetS) or a low
      ankle brachial index (ABI), respectively, to identify patients with high risk for
      cardiovascular events has repeatedly been postulated. However, robust data on the
      prevalence and prognosis of such patients are missing in the primary care
      setting. PATIENTS AND METHODS: In the prospective, non-interventional "German
      epidemiological trial on Ankle Brachial Index (getABI) at total of 6880
      unselected patients > or = 65 years were observed by their General Practitioners
      over 3 years. Death and cardiovascular events were recorded. The definition of
      MetS was similar to the one of NCEP ATP III (National Cholesterol Education
      Program--Adult Treatment Panel III). ABI (ratio of the systolic blood pressures
      measured at the distal part of the calf and at the upper arm) was measured with
      Doppler sonography. Peripheral arterial disease (PAD) was defined as ABI <0.9 or
      peripheral revascularization/amputation owing to PAD. Survival analyses were
      conducted with a Cox proportional hazard model. Hazard rate ratios (HRR, 95 %
      confidence intervals, CI) were multvariate adjusted. RESULTS: The observation
      time for the total cohort was more than 20,000 patient years (PY). Cardiovascular
      mortality in patients with MetS (n = 3040, 44 %) compared to patients without
      MetS (n = 3795; 55 %) was doubled (8.5 vs. 4.0 per 1,000 PY; HRR: 2.0; CI 1.3 -
      2.9). Concomitant presence of MetS and PAD (n = 651; 9.5 %) increased the
      mortality risk compared to patients without both conditions (n = 3194; 46.4 %)
      drastically (21.1 vs. 3.0 per 1000 PY; HRR: 5.7; CI: 3.5 - 9.4). Similar
      significant risk increases also were noted for all-cause mortality or a combined
      endpoint of mortality and vascular morbidity. Further, in lower ABI categories
      cardiovascular event rates increased. CONCLUSIONS: Patients with MetS carry a
      substantially increased risk of premature death, especially cardiovascular death,
      and therefore require intensive treatment of their risk factors. This holds
      especially true if concomitant PAD is present.

PMID- 17187319
TI  - [Isoniazid intoxication].
AB  - HISTORY AND ADMISSION FINDINGS: A 55-year-old woman presented with sustained
      convulsions after the ingestion of an at first unknown amount of isoniazid,
      rifampin, ethambutol and alcohol. INVESTIGATION: At admission the patient had a
      severe metabolic acidosis. Blood tests showed changes caused by the
      hepatotoxicity of isoniazid. TREATMENT AND COURSE: Because diazepam was not
      efficacious in controlling the convulsions the patient was intubated. In response
      to the therapautic measures the convulsions stopped and metabolic acidosis was
      quickly compensated. Pyridoxine was given intravenously as an antidote.
      CONCLUSION: The rare intoxication with isoniazid demands immediate administration
      of pyridoxine and aggressive treatment of the convulsions.

PMID- 17187320
TI  - [Acute cardiogenic pulmonary edema: value of non-invasive ventilation].

PMID- 17187321
TI  - [Subileus caused by foreign body ingestion].

PMID- 17187323
TI  - [Compliance after organ transplantation--influence of quality of life and of the
      physician-patient relationship].

PMID- 17187322
TI  - [beta(2)-Sympathomimetics: risks for asthma therapy? Lessons from the SMART1
      Study. A statement from the German Respiratory Tract League].

PMID- 17187324
TI  - [Medical innovations in the age of diagnosis-related groups (DRGs)].

PMID- 17187326
TI  - [Bone marrow puncture].

PMID- 17187327
TI  - [Cardio-embolic events also caused by thrombosis of the right heart atrial
      appendage?].

PMID- 17187328
TI  - [Rupture of the rotator cuff].
AB  - Reconstructive surgery of rotator cuff tears tries to restore a stable center of
      rotation in the shoulder joint. Both the classic technique of open surgery and
      the arthroscopic technique are employed to reconstruct the rotator cuff. This
      review tries to answer the question which of both surgical techniques is superior
      by a review of the literature. The recent literature demonstrates a shorter
      follow-up period for publications concerning arthroscopic reconstruction (mean 3
      years) in comparison to open surgery, where follow-up is in mean 6.2 years.
      Overall arthroscopic surgery achieves good and excellent results between 68 to
      96%, open reconstruction between 77 and 91%. Longevity of reconstructed rotator
      cuffs especially in large tears seems to be significantly shorter if an
      arthroscopic technique was used. Several authors mentioned size of tear as a
      major factor influencing longevity. However in patients treated arthroscopically
      despite rerupture of the rotor cuff patient's satisfaction and clinical outcome
      is still very good in short-term follow-up. In case of a complete tear of one
      tendon of the rotator cuff the arthroscopic technique seems to be superior. If
      large tears occur (two or three tendons) the open surgical technique may be more
      reliable with regard to longevity of the repair. For the future it seems
      necessary to obtain long-term results to be able to compare both principles of
      reconstruction of the rotator cuff. Furthermore these future studies should
      include quality of life scores as measurements tools besides the already employed
      parameters as size of the tear, age at surgery, patient satisfaction and outcome
      scores.

PMID- 17187329
TI  - [Is there evidence in evidence-based medicine? A comparison of common gradation
      systems and critical evaluation].
AB  - AIM: Evidence-based medicine is still discussed controversially. The current
      literature offers a huge amount of tables, recommendations and modifications for
      the levels of evidence and degrees of recommendations. The scientist who is
      critical of new techniques and who wants to continue his education might be
      confused by the different recommendations. Unfortunately, the gradation of the
      recommendations is not always cited which has led to the controversially held
      discussion about evidence-based medicine. It was, therefore, the aim of the
      current article to present the most often used gradations and to discuss them
      critically. METHOD: In the current study we performed an analysis of the
      currently used recommendations and gradations in evidence-based medicine and
      discussed them critically. RESULTS: The great number of the available divisions
      to evidence-based medicine are often technical and partially differ considerably.
      An unambiguous assignment of the evidence classes and of recommendation degrees
      can only succeed if the source is indicated clearly. CONCLUSION: As far as the
      authors are concerned, the confusing status of evidence-based medicine makes one
      gradation necessary, which should be accepted and used worldwide.

PMID- 17187330
TI  - [Effects of inpatient rehabilitation for patients with back pain].
AB  - BACKGROUND: This prospective, randomised longitudinal study examined the effects
      of inpatient medical rehabilitation. METHOD: Data was collated on the day of
      admission (n=261), day of discharge (n=261) and 6 months after discharge (n=243).
      The length of the rehabilitation measure changed every 3 months from 3 weeks
      (n=127) to 4 weeks (n=134) and back again. On all three specific days the VAS,
      the Roland-Morris-Questionnaire (RMQ) and the SF-36 were applied. The distance
      between fingers and floor and the Schober-sign were measured on the first and
      second day. The Mainz Pain Staging System (MPSS) was used to classify pain
      chronicity. RESULTS: On the day of discharge all parameters show an improvement.
      When the differing rehabilitation times are compared we can see the longer period
      scores better in VAS and Schober. 6 months after the rehabilitation all
      parameters show a slight improvement over the first day--except VAS--and a
      deterioration compared to the second--except RMQ. No significant predominance of
      the 4 week rehabilitation period is recognizable. CONCLUSION: The length of the
      rehabilitation measure alone seems to have no real effect on the permanence of
      the positive treatment of back complaints. It has advantages, though, for the
      result on the day of discharge.

PMID- 17187331
TI  - [Health-economic considerations for the use of BMP-2 for spinal surgery in
      Germany].
AB  - INTRODUCTION: BMP-2 can replace autogenous bone grafting in lumbar one-level
      anterior lumbar interbody fusions (ALIF). The current G-DRG system does not
      reimburse the upfront price of 2,970 euro per BMP-2 application for hospitals in
      Germany. The purpose of the current study was to create a health economic model
      to evaluate the financial savings for health care providers (hospitals) and
      health care payers (health care insurance) that can be achieved by the use of BMP
      2 in spine surgery. METHODS: A previously published pooled data analysis was used
      in which BMP-2 showed significant improvements in the treatment after ALIF
      surgery compared to autogenous bone grafting, including earlier return to work
      time and reduced revision rates. These medical findings were transformed into
      economic data based on the regulations of the German health system of 2005.
      RESULTS: The significantly shorter return to work time under BMP-2 treatment
      generates important financial savings for health care insurances offsetting the
      upfront prize of 2,970 euro for BMP-2. Savings for hospitals are mainly related
      to shorter surgery time due to the absence of the bone grafting procedure and
      faster discharge of the patient. CONCLUSIONS: The combination of improved medical
      outcome by BMP-2 treatment for the patient and net savings for the entire health
      care system in Germany represents a "dominant" strategy from a health economic
      perspective. This implicates that BMP-2 in ALIF procedures is to be recommended
      from a health economic point of view for the German health care system.

PMID- 17187332
TI  - [Rare differential diagnosis of a radicular spine syndrome: herpes zoster
      radiculitis].
AB  - We report on the case of a 66-year-old patient who was hospitalized because of
      intractable low back pain radiating into the right leg. Leg pain was accompanied
      by a numbness and muscle weakness which was clearly assigned to the L5 dermatome.
      Concerning the patient's medical history a nucleotomy L4/5 and a
      osteomyelofibrosis were known. MRI of the lumbar spine revealed a multisegmental
      stenosis which was pronounced on the level L4/5. One day after admission of the
      patient to the hospital a typical zoster exanthema involving the L5 dermatome
      appeared. Varicella-zoster virus (VZV) was detected in the fluid of the vesicular
      skin lesions by polymerase chain reaction. Intravenous administration of
      aciclovir lead to rapid decrease of pain and exanthema. A few months later the
      patient died because of an acute myeloid leukemia as a complication of the known
      osteomyelofibrosis. This case report shows that a herpes zoster infection can
      imitate a radicular spine syndrome usually caused by degenerative changes.
      Especially in immunocompromised patients, a zoster radiculitis should be included
      in the differential diagnosis of radiculopathy. VZV infection might also occur
      without skin lesions (zoster sine herpete) so that serological assays for the
      early detection of virus DNA can be useful.

PMID- 17187333
TI  - [Primary stability of cementless implanted hip stems made of titanium alloy with
      metaphyseal fixation. A prospective clinical Roentgen-Stereometry-Analysis (RSA)
      study].
AB  - AIM: Under early mobilisation and full weightbearing the primary stability of two
      different cementless hip stems should be examined by using Roentgen Stereometric
      Analysis (RSA). METHOD: 26 patients (slashed circle 60.8+/-7.5 J., 16 m, 10 w,
      BMI 27.7+/-3.9 kg/m2) received a total hip arthroplasty with an anatomical
      designed image-stem (IS) (Smith & Nephew, Schenefeld, Germany), 20 patients
      (slashed circle 60.0+/-10.9 J., 12 m, 8 w, BMI 27.5+/-3 .7 kg/m2) the Bicontact
      stem (BS) (Aesculap, Tuttllingen, Germany). RSA measurements were done before
      mobilizing, 3 and 6 weeks, 3, 6, 12 and 24 months postoperatively. Furthermore
      the patients had to estimate their pain on a visually scale (VAS). We registrated
      the Harris-Hip-Score (HHS) and the Western Ontario and McMasters Universities
      Osteoarthritis Index (WOMAC). RESULTS: Both stems showed the maximum of
      subsidence in the first 3 months (IS 0.647 mm, BS 0.54 mm). 6 months
      postoperative the measured migrations were in the range of the accuracy. After 2
      years the subsidence was 1.07 mm+/-0.07 mm for the IS-group, 0.97 mm+/-0.18 mm
      for the BS-group. There were no significant differences in the examined
      parameters between the both groups. An excellent prostheses function and high
      activity grade with a high WOMAC score, a high HHS and a low VAS was founded for
      both groups. CONCLUSION: Both cementless implanted titanium hip stems showed a
      sufficient primary and midterm stability with excellent clinical results. The
      measured migrations do not differ from those given in literature for cemented
      stems.

PMID- 17187334
TI  - [Biomechanical evaluation of the gliding nail in trochanteric fractures].
AB  - AIM: The purpose of the present study is to evaluate wether the gliding nail with
      it's double-t-shaped geometry is appropriate in the stabilization of unstable
      trochanteric fractures or not and if this evaluation can be performed with a
      static finite element simulation. METHODS: Surface-Reconstruction with CT
      database of a proximal femur and reconstruction with CT based density data was
      done. After modelling of geometry, isotropic material behaviour and load
      application during one leg standing in slow walking was done with a limited
      dataset of relevant muscles. Two relevant fractures are modelled. RESULTS: FE
      simulation shows a movement of the femoral head distally, medially and
      posteriorly. Maximum bending strain is in the femoral diaphysis medial
      compression and lateral tension strain. In the proximal part we find a nearly
      homogeneous strain distribution. The clinical effect of lateralization of the
      proximal main fragment is also result of the simulation. In the area of the
      modelled fractures there is much more compressive stress than shear stress.
      CONCLUSION: Elastomechanical behaviour of the gliding nail is demonstrated with
      correlation of clinical observed effects. In both simulated fracture areas there
      is a bone union supporting compressive stress. This means in the FE-simulation
      the gliding nail is appropriate in the stabilization in unstable trochanteric
      fractures.

PMID- 17187336
TI  - [First results after implantation of a pyrocarbon-endoprosthesis in patients with
      degenerative arthritis].
AB  - AIM: Evaluation of an unconstrained pyrocarbon prosthesis (Ascension) in the
      treatment of idiopathic degenerative arthritis of the proximal interphalangeal
      joint of the hand. METHODS: In this study 10 patients (13 implants), that were
      treated with this type of prosthesis between February 2002 and January 2005 were
      clinically and radiologically studied. RESULTS: All but one patient were
      satisfied with the postoperative situation and would agree to another operation.
      A significant pain reduction was observed. The average ROM was 58 degrees. Five
      patients demonstrated a free extension, two patients had a swan neck deformity,
      which could be actively compensated for, and the remaining six patients had an
      extension deficit of 30-45 degrees. The average flexion was 76 degrees (+/-12
      degrees). X-ray examination was unremarkable in eight patients with a regular
      position of the endoprosthesis. However, in five patients significant radiolucent
      lines (>or=1 mm) were observed. So far, a luxation of the prosthesis has not
      occurred and all implants are still in-situ. However, a dorsal tenoarthrolysis
      had to be performed in 3 patients. CONCLUSION: The results of this study show a
      high rate of patient satisfaction with a significant pain reduction. A missing
      osteointegration may be an explanation for the radiological results. The
      prosthesis has to be closely monitored in the future. Long-term results with a
      higher number of patients are necessary. A central registry for finger implants
      is recommended.

PMID- 17187335
TI  - [Results of vacuum sealing therapy in joint infections].
AB  - AIM: At present the vacuum sealing technique is acknowledged as a therapy for
      acute and chronic wounds. An acceleration of the healing process, due to the
      vacuum suction with occlusive wound dressing, leads to the shortening of a cost
      effective medical treatment. This can be applied to wound treatment and
      infections of soft tissues, but even today there is only sparse information in
      this context about joint infections. METHOD: The results of therapy with the
      vacuum sealing technique in 68 patients with infections of the joints of an
      extremity or the trunk were analysed in a retrospective study without a control
      group. The importance of several patient-related factors for the medical
      treatment have been analysed. RESULTS: An adequate treatment of joint infections
      can be achieved even in the presence of endoprostheses or osteosynthetic
      material. The following factors have been found to be of significance for a
      prolonged medical treatment: diabetes mellitus (p=0.0052), obesity (BMI>25)
      (p=0.0458) and a preceding trauma (p=0.0457). CONCLUSION: The results confirm the
      value of the vacuum sealing technique following surgical debridement in
      combination with resistance tested antibiotic treatment, as a sufficient therapy
      for joint infections, even in patients with an endoprosthesis. This procedure
      leads to a safe treatment of the joint infection, combined with a good function
      of the treated joint, good patient comfort and a short duration of the therapy.

PMID- 17187337
TI  - [Operative treatment of ruptures of distal tendon of biceps muscle with a
      minimally invasive technique using suture anchors--clinical results].
AB  - AIM: Ruptures of the distal tendon of the biceps muscle should be treated
      operatively. A minimally invasive technique and the use of suture anchors may
      decrease the intraoperative risks. But can satisfactory clinical results be
      achieved? METHOD: We present the results of a clinical study. Between 1999 and
      2005 nine patients were operated for distal biceps tendon avulsion. A minimally
      invasive operating technique using a suture anchor was established and the
      technique is described. Rantanen and Orava's score was used to compare clinical
      and radiological findings. RESULTS: Clinical follow-up was performed at 6 months
      after operation. In six patients excellent results according to Rantanen and
      Orava were achieved. No loss of strength was noticed in 6 of 9 cases. Range of
      motion was unlimited in six patients. In two cases we found heterotopic
      ossifications. CONCLUSION: On the basis of our results we suggest that minimally
      invasive surgery using a suture anchor should be performed more often. The
      technique described leads to results that are comparable to those found in the
      literature.

PMID- 17187338
TI  - [The acquired flatfoot: mid-term results of the medial displacement calcaneal
      osteotomy with flexor digitorum longus transfer].
AB  - AIM: The present retrospective study investigates the mid-term results after
      medial displacement calcaneal osteotomy combined with flexor digitorum longus
      transfer for the treatment of acquired flatfoot deformity due to posterior tibial
      tendon insufficiency at stage II (Johnson and Strom Classification). METHOD: 30
      feet in 29 patients (6 male, 23 female) with an average age of 58 years (from 43
      to 68 years) had surgery between 1995 and 2001. All feet were examined at an
      average follow-up of 58.5 months (range 35-97 months) and were evaluated with the
      American-Orthopaedic-Foot and Ankle Society (AOFAS) Hindfoot-Score. RESULTS: The
      average AOFAS-Score was 88.8+/-10.7 points (range 48 to 100) at final follow-up.
      The AOFAS-pain-subscale score was 34+/-6.2 points. At the latest follow-up were
      14 feet (47%) painfree, 14 feet (47%) noted mild pain and 2 feet (6%) had daily
      pain. One foot (3%) had pain due to subluxation of the musculus flexor digitorum
      longus tendon, in another one pain was caused by a contract Chopart joint (3%).
      Further complications were painful prominent hardware (17%) and neuralgia of the
      sural nerve (7%). CONCLUSION: The authors conclude that the combination of the
      medial calcaneal displacement osteotomy with flexor digitorum longus transfer may
      provide optimal results in patients with adult acquired flatfoot deformity and
      posterior tibialis tendon dysfunction.

PMID- 17187339
TI  - [Biomechanical evaluation of biointegrable suture anchors composed of bovine
      compact bone in a pull-to-failure test in porcine tibial head specimens].
AB  - AIM: Suture anchors of various designs have gained wide acceptance for securing
      soft tissues to bone. The biointegrable Tutofix CB anchors derived from bovine
      compact bone are available with diameters of 3 mm (CB3 anchor), 4 mm (CB4 anchor)
      and 5 mm (CB5 anchor). The CB anchors are push-in anchors and, from the
      biomechanical standpoint, they are a combination of press-fit and angulation
      anchors. The purpose of this study was to evaluate the CB anchors for singular
      pull load-to-failure strength using porcine tibial head specimens as a test
      model. METHODS: In all specimens, the joint surface was removed by performing a
      subchondral osteotomy. Axial PQ-CT scans of 12 specimens were obtained to
      determine the trabecular BMD. The anchors were implanted posteromedially and
      centrolaterally in the porcine tibial head specimens. After threading the anchors
      with a steel suture and predrilling of the anchor holes perpendicular to the
      osteotomy surface they were inserted 4 mm below the osteotomy surface. A
      universal testing machine applied tensile loads parallel to the axis of insertion
      at rates of 10 mm/min and 500 mm/min until pull-out failure or anchor breakage
      and mean anchor fixation strengths were calculated. RESULTS: The fixation
      strength of the CB anchors was found to be much higher at the dorsomedial
      implantation site than at the centrolateral implantation site. The CB4 anchors
      and CB5 anchors provided nearly the same fixation strength at a level much higher
      than that of the CB3 anchors. Bone mineral density had a strong influence on
      axial pull-out force of the anchors, especially the CB4 anchors and CB5 anchors.
      The overall correlation coefficient for bone mineral density with ultimate load
      to-failure was 0.869 for the CB4 anchors and 0.716 for the CB5 anchors.
      Differences in failure strengths were also seen between the low and high
      extraction rates. With the high extraction rate much higher failure strengths
      were obtained than with the low extraction rate. The sudden pull eccentrically on
      the anchors caused a better fixation due to angulation of the anchor within the
      drill holes. CONCLUSION: In spite of the double worst-case scenario in the
      testing conditions, the CB anchors provided a high fixation strength in the
      trabecular bone of porcine tibial head specimens with the CB4 anchors and CB5
      anchors being nearly equal and both being superior to the CB3 anchors. Bone
      mineral density had a strong influence on the axial pull-out force. Our results
      show that the CB anchors seem to be a reasonable alternative to metal and
      bioabsorbable suture anchors.

PMID- 17187340
TI  - [Comparative in vitro analysis of vacuum plasma-sprayed titanium implants-
      evaluation of OPG, Osteokalzin and AP expression].
AB  - INTRODUCTION: The purpose of this study was to evaluate the influence of
      different surface topographies on the expression of bone cell-associated
      proteins, such as osteoprotegerin (OPG), osteocalcin and alkaline phosphatase
      (AP), and the production of the extracellular matrix (ECM) in vitro. Another
      aspect was the question as to whether a hydroxyapatite (HA) coating offers
      additional advantages. Vacuum plasma-sprayed (VPS) pure titanium was used to
      generate different surface topographies. MATERIALS AND METHODS: The in vitro
      response of human bone marrow cells to VPS implants (porosity ranging from 25 to
      50%, pore size ranging from 50 to 200 microm and roughness ranging from 0.191 to
      0.547 mm) and cancellous structured titanium (cs-Ti) as a reference material (55%
      porosity, pore size of 500 microm, roughness 0.836 mm) were compared. The
      expression of bone cell-associated proteins, such as OPG, osteocalcin and
      alkaline phosphatase (AP), was evaluated. Scanning electron microscopy (SEM) was
      used to judge the production of ECM. RESULTS: All implant materials induced the
      release of OPG, osteocalcin and AP. Significant differences were evident between
      the cs-Ti and the different VPS-Ti surface structures. There was no difference in
      the response between the VPS-Ti surfaces. SEM showed a dense and increased
      production of ECM on the VPS-Ti surfaces. An additional HA coating caused a
      faster production of ECM and higher levels of OPG. CONCLUSIONS: The in vitro data
      presented here demonstrate the superiority of VPS-Ti surfaces over cs-Ti, which
      is already in clinical use. Differences between the VPS-Ti surfaces were not
      evident. Presumably, VPS-Ti surfaces offer good prerequisites for a successful
      integration of the implant in the surrounding tissue. An additional HA coating
      could influence these events positively.

PMID- 17187341
TI  - [Erysipel at the lower leg combined with a peripheral peroneus nerve palsy--an
      unusual occurrence].
AB  - We present the clinical case of a fifty-year-old man who presented two times with
      a foot elevator paresis and an erysipel first on the right and after two months
      on the left side. Afterwards, we carried out a thorough case history with the
      help of clinical, radiological and magnetic resonance imaging. Even so the
      clinical pathology of the foot elevator paresis could not be manifested. A
      compartment syndrome could be discounted. In the context of the second stay
      during a neurology examination on both legs electromyography was performed and
      the nerve speed was tested. A peripheral peroneus paresis of unknown level and of
      unknown aetiology was demonstrated. The erysipel regressed rapidly under
      intravenous ampicillin antibiotics while the peroneus paresis was unchanged. The
      patent was released with a peroneus splint on both sides. With this case report
      we would like to point out the causes of peripheral peroneus paresis with regard
      to an additional erysipel. This case report is discussed regarding the possible
      aetiopathology and the current literature.

PMID- 17187343
TI  - 1H and 13C NMR spectral characterization of some novel 7H-1,2,4-triazolo[3, 4-b]
      [1,3,4] thiadiazine derivatives.
AB  - Some novel 1, 2, 4-triazolo[3,4-b][1,3,4]thiadiazines derivatives were
      synthesized. The complete (1)H and (13)C NMR chemical shift assignments were
      analyzed on one- and two-dimensional NMR techniques, including DEPT, NOE-DIF,
      COSY, HMBC, and HSQC.

PMID- 17187344
TI  - Optimization of in vitro expansion of human multipotent mesenchymal stromal cells
      for cell-therapy approaches: further insights in the search for a fetal calf
      serum substitute.
AB  - There is great interest in mesenchymal stromal cells (MSCs) for cell-therapy and
      tissue engineering approaches. MSCs are currently expanded in vitro in the
      presence of fetal calf serum (FCS); however, FCS raises concerns when used in
      clinical grade preparations. The aim of this study was to evaluate whether MSCs
      expanded in medium supplemented with platelet-lysate (PL), already shown to
      promote MSC growth, are endowed with biological properties appropriate for cell
      therapy approaches. We confirm previously published data showing that MSCs
      expanded in either FCS or PL display comparable morphology, phenotype, and
      differentiation capacity, while PL-MSCs were superior in terms of clonogenic
      efficiency and proliferative capacity. We further extended these data by
      investigating the immune-regulatory effect of MSCs on the alloantigen-specific
      immune response in mixed lymphocyte culture (MLC). We found that MSCs-PL are
      comparable to MSCs-FCS in their capacity to: (i) decrease alloantigen-induced
      cytotoxic activity; (ii) favor differentiation of CD4+ T-cell subsets expressing
      a Treg phenotype; (iii) increase early secretion of IL-10 in MLC supernatant, as
      well as induce a striking augmentation of IL-6 production. As compared with MSCs
      PL, MSCs-FCS were more efficient in suppressing alloantigen-induced lymphocyte
      subset proliferation and reducing early IFNgamma-secretion. Resistance to
      spontaneous transformation into tumor cells of expanded MSCs was demonstrated by
      molecular karyotyping and maintenance of normal morphology/phenotype after
      prolonged in vitro culture. Our data support the immunological functional
      plasticity of MSCs and suggest that MSCs-PL can be used as an alternative to MSCs
      FCS, although these latter cells might be more suitable for preventing/treating
      alloreactivity-related immune complications.

PMID- 17187346
TI  - Continuous requirement for pp60-Src and phospho-paxillin during fibronectin
      matrix assembly by transformed cells.
AB  - Fibronectin (FN) matrix assembly is an integrin-mediated process that is
      regulated by both the extracellular environment and intracellular signaling
      pathways. The activity of Src-family kinases is important for initiation of FN
      assembly by normal fibroblasts. Here we report that in HT1080 fibrosarcoma cells,
      Src kinase activity is required not only for the assembly of FN matrix but also
      for the maintenance of FN matrix fibrils at the cell surface. Dexamethasone
      induced FN fibril formation by these cells was completely blocked for at least 24
      h when Src-family kinase activity was inhibited by either PP1 or SU6656.
      Inhibition of Src after significant matrix had already been assembled, resulted
      in an increased rate of loss of detergent-insoluble FN. Binding of activation
      dependent integrin antibodies reveals a role for Src in maintaining integrin
      activity. The requirement for Src kinase activity appears to depend, in part, on
      phosphorylation of paxillin at tyrosine 118 (Y118). Phospho-paxillin co-localized
      with FN fibrils, and overexpression of GFP-paxillin but not of GFP-paxillinY118F
      enhanced cell-mediated assembly of FN. Our results indicate that Src maintains FN
      matrix at the cell surface through its effect on integrin activity and paxillin
      phosphorylation.

PMID- 17187347
TI  - The performance of different propensity score methods for estimating marginal
      odds ratios.
AB  - The propensity score which is the probability of exposure to a specific treatment
      conditional on observed variables. Conditioning on the propensity score results
      in unbiased estimation of the expected difference in observed responses to two
      treatments. In the medical literature, propensity score methods are frequently
      used for estimating odds ratios. The performance of propensity score methods for
      estimating marginal odds ratios has not been studied. We performed a series of
      Monte Carlo simulations to assess the performance of propensity score matching,
      stratifying on the propensity score, and covariate adjustment using the
      propensity score to estimate marginal odds ratios. We assessed bias, precision,
      and mean-squared error (MSE) of the propensity score estimators, in addition to
      the proportion of bias eliminated due to conditioning on the propensity score.
      When the true marginal odds ratio was one, then matching on the propensity score
      and covariate adjustment using the propensity score resulted in unbiased
      estimation of the true treatment effect, whereas stratification on the propensity
      score resulted in minor bias in estimating the true marginal odds ratio. When the
      true marginal odds ratio ranged from 2 to 10, then matching on the propensity
      score resulted in the least bias, with a relative biases ranging from 2.3 to 13.3
      per cent. Stratifying on the propensity score resulted in moderate bias, with
      relative biases ranging from 15.8 to 59.2 per cent. For both methods, relative
      bias was proportional to the true odds ratio. Finally, matching on the propensity
      score tended to result in estimators with the lowest MSE.

PMID- 17187345
TI  - Evidence for BAG3 modulation of HIV-1 gene transcription.
AB  - A family of co-chaperone proteins that share the Bcl-2-associated athanogene
      (BAG) domain are involved in a number of cellular processes, including
      proliferation and apoptosis. Among these proteins, BAG3 has received increased
      attention due to its high levels in several disease models and ability to
      associate with Hsp70 and a number of other molecular partners. BAG3 expression is
      stimulated during cell response to stressful conditions, such as exposure to high
      temperature, heavy metals, and certain drugs. Here, we demonstrate that BAG3
      expression is elevated upon HIV-1 infection of human lymphocytes and fetal
      microglial cells. Furthermore, BAG3 protein was detectable in the cytoplasm of
      reactive astrocytes in HIV-1-associated encephalopathy biopsies, suggesting that
      induction of BAG3 is part of the host cell response to viral infection. To assess
      the impact of BAG3 upregulation on HIV-1 gene expression, we performed
      transcription assays and demonstrated that BAG3 can suppress transcription of the
      HIV-1 long terminal repeat (LTR) in microglial cells. This activity was mapped to
      the kappaB motif of the HIV-1 LTR. Results from in vitro and in vivo binding
      assays revealed that BAG3 suppresses interaction of the p65 subunit of NF-kappaB
      with the kappaB DNA motif of the LTR. Results from binding and transcriptional
      assay identified the C-terminus of BAG3 as a potential domain involved in the
      observed inhibitory effect of BAG3 on p65 activity. These observations reveal a
      previously unrecognized cell response, that is, an increase in BAG3, elicited by
      HIV-1 infection, and may provide a new avenue for the suppression of HIV-1 gene
      expression.

PMID- 17187348
TI  - The Assessment of Depression Inventory (ADI): an appraisal of validity in an
      outpatient sample.
AB  - In this study we examined the validity of the Assessment of Depression Inventory
      (ADI) using outpatient participants. The ADI Depression scale (Dep) was compared
      to three other measures used to assess depression: Beck Depression Inventory-II
      (BDI-II), Zung Self-Rating Depression Scale (ZSDS), and Personality Assessment
      Inventory (PAI). Correlations between the ADI and these three measures were
      significant. An analysis of the discriminant ability of the ADI Dep scale
      resulted in sensitivities, specificities, positive predictive power, negative
      predictive power, hit rate, and area under the curve (92.3%) that were supportive
      of the scale's effectiveness. The ADI Feigning scale (Fg) was compared to the six
      PAI validity scales. The Fg scale correlated significantly with the PAI Negative
      Impression Management (NIM) and Positive Impression Management (PIM) scales, and
      the Malingering (MAL) and Defensive (DEF) indexes. Directionality was as would be
      predicted. The ADI did not correlate with the two PAI validity scales derived by
      discriminant analysis function.

PMID- 17187350
TI  - How to tweak a beak: molecular techniques for studying the evolution of size and
      shape in Darwin's finches and other birds.
AB  - A flurry of technological advances in molecular, cellular and developmental
      biology during the past decade has provided a clearer understanding of mechanisms
      underlying phenotypic diversification. Building upon such momentum, a recent
      paper tackles one of the foremost topics in evolution, that is the origin of
      species-specific beak morphology in Darwin's finches.1 Previous work involving
      both domesticated and wild birds implicated a well-known signaling pathway (i.e.
      bone morphogenetic proteins) and one population of progenitor cells in particular
      (i.e. cranial neural crest), as primary factors for establishing beak size and
      shape. But these results were limited in their ability to explain fully the
      morphogenetic bases of patterned outgrowth. So in a quest to identify novel genes
      whose expression correlated with differences in beak anatomy among Darwin's
      finches, a DNA microarray approach was undertaken using tissues harvested from
      the Galapagos Islands. The results are striking and point to a protein called
      calmodulin, which is a mediator of cellular calcium signaling, as a key
      determinant of beak length.

PMID- 17187349
TI  - Symptom features of postpartum depression: are they distinct?
AB  - The clinical features of postpartum depression and depression occurring outside
      of the postpartum period have rarely been compared. The 16-item Quick Inventory
      of Depressive Symptomatology-Self-Report (QIDS-SR(16)) provides a means to assess
      core depressive symptoms. Item response theory and classical test theory analyses
      were conducted to examine differences between postpartum (n=95) and nonpostpartum
      (n=50) women using the QIDS-SR(16). The two groups of females were matched on the
      basis of age. All met DSM-IV criteria for nonpsychotic major depressive disorder.
      Low energy level and restlessness/agitation were major characteristics of
      depression in both groups. The nonpostpartum group reported more sad mood, more
      suicidal ideation, and more reduced interest. In contrast, for postpartum
      depression sad mood was less prominent, while psychomotor symptoms
      (restlessness/agitation) and impaired concentration/decision-making were most
      prominent. These symptomatic differences between postpartum and other depressives
      suggest the need to include agitation/restlessness and impaired
      concentration/decision-making among screening questions for postpartum
      depression.

PMID- 17187351
TI  - Chromatin looping mediates boundary element promoter interactions.
AB  - One facet of the control of gene expression is long-range promoter regulation by
      distant enhancers. It is an important component of the regulation of genes that
      control metazoan development and has been appreciated for some time but the
      molecular mechanisms underlying this regulation have remained poorly understood.
      A recent study by Cleard and colleagues1 reports the first in vivo evidence of
      chromatin looping and boundary element promoter interaction. Specifically, they
      studied the function of a boundary element within the cis-regulatory region of
      the Abdominal-B (Abd-B) gene of Drosophila melanogaster.

PMID- 17187352
TI  - Metagenomic studies reveal the critical and wide-ranging ecological importance of
      uncultivated Archaea: the role of ammonia oxidizers.
AB  - Microbial genome sequencing has entered a new phase, where DNA sequence
      information is gathered from entire microbial communities (metagenomics or
      environmental genomics) rather than from individual microorganisms. By providing
      access to the genetic material of vast numbers of organisms, most of which are
      organisms that have never been isolated or cultivated, a new level of insight is
      being gained into the diversity and extent of the microbial processes that are
      presently occuring in environmental communities. By extending metagenomic-based
      approaches to the study of very complex and methodologically recalcitrant soil
      environments, a recent study has found that ammonia-oxidizing archaea are more
      abundant in many soils than bacteria.1 These findings not only highlight the
      undoubtedly critical yet unknown roles that archaea play in global nutrient
      cycles but illustrate the importance of genomic studies for informing us about
      the functional capacity of life on Earth.

PMID- 17187353
TI  - Early frontotemporal dementia targets neurons unique to apes and humans.
AB  - OBJECTIVE: Frontotemporal dementia (FTD) is a neurodegenerative disease that
      erodes uniquely human aspects of social behavior and emotion. The illness
      features a characteristic pattern of early injury to anterior cingulate and
      frontoinsular cortex. These regions, though often considered ancient in
      phylogeny, are the exclusive homes to the von Economo neuron (VEN), a large
      bipolar projection neuron found only in great apes and humans. Despite progress
      toward understanding the genetic and molecular bases of FTD, no class of
      selectively vulnerable neurons has been identified. METHODS: Using unbiased
      stereology, we quantified anterior cingulate VENs and neighboring Layer 5 neurons
      in FTD (n = 7), Alzheimer's disease (n = 5), and age-matched nonneurological
      control subjects (n = 7). Neuronal morphology and immunohistochemical staining
      patterns provided further information about VEN susceptibility. RESULTS: FTD was
      associated with early, severe, and selective VEN losses, including a 74%
      reduction in VENs per section compared with control subjects. VEN dropout was not
      attributable to general neuronal loss and was seen across FTD pathological
      subtypes. Surviving VENs were often dysmorphic, with pathological tau protein
      accumulation in Pick's disease. In contrast, patients with Alzheimer's disease
      showed normal VEN counts and morphology despite extensive local neurofibrillary
      pathology. INTERPRETATION: VEN loss links FTD to its signature regional pattern.
      The findings suggest a new framework for understanding how evolution may have
      rendered the human brain vulnerable to specific forms of degenerative illness.

PMID- 17187354
TI  - Evaluating hypotheses for the origin of eukaryotes.
AB  - Numerous scenarios explain the origin of the eukaryote cell by fusion or
      endosymbiosis between an archaeon and a bacterium (and sometimes a third
      partner). We evaluate these hypotheses using the following three criteria. Can
      the data be explained by the null hypothesis that new features arise sequentially
      along a stem lineage? Second, hypotheses involving an archaeon and a bacterium
      should undergo standard phylogenetic tests of gene distribution. Third,
      accounting for past events by processes observed in modern cells is preferable to
      postulating unknown processes that have never been observed. For example, there
      are many eukaryote examples of bacteria as endosymbionts or endoparasites, but
      none known in archaea. Strictly post-hoc hypotheses that ignore this third
      criterion should be avoided. Applying these three criteria significantly narrows
      the number of plausible hypotheses. Given current knowledge, our conclusion is
      that the eukaryote lineage must have diverged from an ancestor of archaea well
      prior to the origin of the mitochondrion. Significantly, the absence of
      ancestrally amitochondriate eukaryotes (archezoa) among extant eukaryotes is
      neither evidence for an archaeal host for the ancestor of mitochondria, nor
      evidence against a eukaryotic host.

PMID- 17187355
TI  - Alterations in cell proliferation and apoptosis in colon cancers with
      microsatellite instability.
AB  - Colon cancers with microsatellite instability (MSI) demonstrate a host immune
      response characterized by tumor infiltrating lymphocytes (TILs) that may exert
      effects upon tumor cell apoptosis and cell proliferation. Accordingly, we
      compared rates of apoptosis and cell proliferation in colon cancers with
      defective DNA mismatch repair and their association with phenotypic features and
      clinical outcome. Primary Astler-Coller stage B2 and C colon carcinomas (n = 329)
      were analyzed for MSI and for hMLH1 and hMSH2 protein expression. Apoptosis
      (TUNEL assay) and p53 expression were also analyzed by immunohistochemistry, and
      TILs were quantified by morphology. DNA ploidy and proliferation (PI: S phase +
      G(2)M) were evaluated using flow cytometry. MSI-H (n = 58) colon cancers showed
      increased TILs that were significantly associated with increased apoptosis,
      higher apoptosis to proliferation (AI/PI) ratios, reduced proliferative indices
      (PI) and diploid DNA content. Increased TILs (p = 0.036) and reduced PI (p =
      0.042), but not AI or AI/PI, were associated with improved disease-free survival.
      Tumors with MSI-H (p = 0.032) or loss of hMLH1 or hMSH2 proteins (p = 0.040), or
      diploidy (p = 0.0015), had better adjusted overall survival rates. Interestingly,
      similar rates of cell turnover and overlapping survival rates were found in
      diploid MSS/MSI-L tumors and in MSI-H cases. In conclusion, higher
      apoptosis/proliferation ratios and reduced cell proliferation are phenotypic
      features of MSI-H tumors that are associated with increased TILs, indicating an
      activated immune response that may contribute to their favorable survival rates.

PMID- 17187356
TI  - Determination and stability of sex.
AB  - How is the embryonic bipotential gonad regulated to produce either an ovary or a
      testis? In males, transient early activation of the Y chromosome Sry gene makes
      both germ cells and soma male. However, in females, available evidence suggests
      that the process of ovary sex determination may take place independently in the
      germline and somatic lineages. In addition, in contrast to testis, in ovary
      somatic cells, female-to-male gonadal sex reversal can occur at times throughout
      ovary development and maturation. We suggest that a single gene pathway, likely
      hinging on the Foxl2 transcription factor, both initiates and maintains sex
      differentiation in somatic cells of the mammalian ovary.

PMID- 17187357
TI  - Biomechanical properties of intermediate filaments: from tissues to single
      filaments and back.
AB  - The animal cell cytoskeleton consists of three interconnected filament systems:
      actin-containing microfilaments (MFs), microtubules (MTs), and the lesser known
      intermediate filaments (IFs). All IF proteins share a common tripartite domain
      structure and the ability to assemble into 8-12 nm wide filaments. Electron
      microscopy data suggest that IFs are built according to a completely different
      plan from that of MFs and MTs. IFs are known to impart mechanical stability to
      cells and tissues but, until recently, the biomechanical properties of single IFs
      were unknown. However, with the discovery of naturally occurring micrometer-wide
      IF bundles and the development of new methodologies to mechanically probe single
      filaments, it is now possible to propose a more unified view of IF biomechanics.
      Unlike MFs and MTs, single IFs can now be described as flexible, extensible and
      tough, which has important implications for our understanding of cell and tissue
      mechanics. Furthermore, the molecular mechanisms at play when IFs are deformed
      point toward a pivotal role for them in mechanotransduction.

PMID- 17187358
TI  - Tumor necrosis factor receptor superfamily member TROY is a novel melanoma
      biomarker and potential therapeutic target.
AB  - Incidence of melanoma continues to rise, and a better understanding of its
      genetics will be critical to improve diagnosis and develop new treatments. Here,
      we search for novel melanoma-specific genes that may serve as biomarkers and
      therapeutic targets by using an in vitro genetic screen. One identified cDNA
      encoded TROY, a member of the tumor necrosis factor receptor superfamily
      (TNFRSF). TROY is widely expressed during embryogenesis, but in adults expression
      is restricted to hair follicles and brain. However, TROY had never been
      associated with melanoma, and it was selected for further study. First we show
      that expression in melanoma is specific by semiquantitative RT-PCR analysis of a
      large panel of established tumor cell lines. Next, specificity of expression was
      evaluated by immunohistochemistry analysis of primary cell cultures and patient
      tissues. TROY is expressed in 2/2 primary melanoma cells and 45/45 melanoma
      tissue samples (p < 0.0001). With the exception of sebaceous glands, TROY is not
      expressed in normal skin biopsies (p < 0.0001) or primary skin cell cultures that
      contain keratinocytes and epidermal melanocytes, nor is it expressed in other
      skin tumor cells (p < 0.0001). Finally, we show that TROY regulates melanoma
      growth, because replication of melanoma cells with reduced TROY levels through
      treatment with short-interfering RNA was significantly decreased relative to
      control cells (p < 0.004). In summary, TROY is the first TNFRSF member that is a
      biomarker for melanoma. TROY also presents a potentially novel cell surface
      signaling target for inhibitors, cell and/or antibody-based immunotherapies.

PMID- 17187359
TI  - Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of
      gastric cancer in a Chinese population.
AB  - Growing evidence suggests that the transforming growth factor beta (TGF-beta)
      signaling pathway occupies a central position in the signaling networks that
      control cell growth and differentiation. TGF-beta1 and its receptor TGF-betaRII
      have been correlated with the development of certain forms of cancer, including
      gastric cancer. We hypothesized that functional genetic variants in TGFB1 and
      TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we
      genotyped C-509T and Leu10Pro polymorphisms in TGFB1 and G-875A variant in
      TGFBR2, using the primer-introduced restriction analysis (PIRA)-PCR assay, in a
      case-control study of 675 gastric cancer cases and 704 healthy controls in a
      Chinese population. We found that the variant alleles of the promoter
      polymorphisms, TGFB1 C-509T and TGFBR2 G-875A, were associated with a
      significantly decreased risk of gastriccancer [adjusted odds ratio (OR) = 0.65,
      95% confidence interval (CI) = 0.52-0.82 for -509CT/TT and adjusted OR = 0.67,
      95% CI = 0.53-0.85 for -875GA/AA]. Furthermore, subjects with both variant
      genotypes of the TGFB1 C-509T and TGFBR2 G-875A were associated with a
      significantly (56%) decreased risk of gastric cancer (adjusted OR = 0.44, 95% CI
      = 0.32-0.62). These findings indicate, for the first-time, that the functional
      variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer
      susceptibility.

PMID- 17187361
TI  - EMP3 overexpression is associated with oligodendroglial tumors retaining
      chromosome arms 1p and 19q.
AB  - The epithelial membrane protein 3 (EMP3) gene located on chromosome 19q13 has
      been implicated as a candidate tumor suppressor gene (TSG) in neuroblastomas and
      gliomas. The aim of this study was to investigate whether EMP3 is involved in
      oligodendroglial tumors (OTs), which frequently carry combined chromosomes 1p and
      19q deletion. We first investigated the transcript level of EMP3 in a cohort of
      57 OTs by quantitative real-time RT-PCR. Our results showed that 10 (18%) tumors
      had reduced EMP3 expression level compared to normal brains. Six of these tumors
      carried chromosome 19q13 deletion but no statistical correlation was found
      between the 2 parameters. Intriguingly, a similar proportion (11 of 57, 19%) of
      tumors displayed EMP3 overexpression, with 8 of them having transcript level >10
      fold higher than normal brain. All 11 OTs retained chromosomes 1p36 and 19q13,
      and a significant association was found between EMP3 overexpression and balanced
      chromosomes 1p36 and 19q13 (p = 0.004). The methylation status of EMP3 was
      evaluated by bisulfite sequencing in 29 OTs with diverse expression levels. All
      tumors except 3 showed aberrant methylation of EMP3 and no correlation was
      observed between transcript level and methylation status, suggesting that
      methylation alone does not mediate transcriptional down-regulation of EMP3 in
      OTs. In conclusion, our study demonstrates that EMP3 overexpression is involved
      in OTs retaining chromosomes 1p and 19q and does not support EMP3 as the target
      TSG on chromosome 19q13 in OTs.

PMID- 17187360
TI  - High survivin expression is associated with favorable outcome in advanced primary
      oral squamous cell carcinoma after radiation therapy.
AB  - Oral squamous cell carcinoma (OSCC) is a solid neoplasm exhibiting aggressive
      tumor phenotypes with unpredictable biological behavior. Recent studies suggested
      that high expression of the antiapoptotic protein survivin might be associated
      with adverse outcome in oral cancer patients. To investigate, whether increased
      copy numbers of the survivin-encoding gene BIRC5 results in elevated survivin
      levels and whether BIRC5 and survivin could serve as progression markers in the
      clinical course of OSCC, tumor tissue microarray analysis was performed applying
      fluorescence in situ hybridization and immunohistochemistry to 296 OSCC
      specimens. Gene copy number gain of BIRC5 was detected in 33.9% (150/227) of
      cases, which correlated significantly with high UICC stage and the presence of
      lymph node metastases (p = 0.003 and p = 0.001, respectively), but not with
      unfavorable patients' outcome (p > 0.05) in multivariate analysis. High survivin
      expression was found in 67.3% (169/251) of cases to predict increased 5- and 10
      year overall survival of patients in a multivariate model including UICC stage
      and age as covariables (p = 0.035 and p = 0.026, respectively). Within a subgroup
      of patients, who received radiation therapy (n = 121), high survivin expression
      was found to be the only predictor of favorable 3-, 5- and 10-year overall
      survival in a multivariate cox regression analysis including UICC stage and age
      as covariables (p = 0.001, p = 0.004 and p = 0.006, respectively). In conclusion,
      high survivin expression might be useful to identify OSCC patients, who would
      benefit from radiotherapy.

PMID- 17187362
TI  - Pathogenesis and vascular integrity of breast cancer brain metastasis.
AB  - Dogma dictates that brain metastasis originate from the proliferation of
      extravasated tumor cells and that the blood-brain barrier (BBB) prevents the
      delivery of chemotherapeutic drugs to the tumors. The purpose of this study was
      to clarify the relationship between tumor localization and progression and the
      involvement of BBB function in a murine model of breast cancer brain metastasis.
      Green fluorescent protein expressing MDA-MB435 breast cancer cells were injected
      into the left ventricle of nude mice. At various time points, the entire
      vasculature was labeled with rhodamine-conjugated albumin. The tumors and
      vasculature were then imaged by laser-scanning confocal and stereo fluorescence
      microscopy. About 75% of the cells that reached the brain extravasated and grew
      perivascularly. Twenty five percent of the cells, however, proliferated within
      the vasculature and ultimately led to thrombosis-like infarction of the brain
      parenchyma. The tumorigenic "embolus" served as a sustained release source of
      tumor cells to downstream sites. Continuing intravascular tumor expansion led to
      disruption of the BBB and to overflow of cells that progressed along the vessels
      perivascularly to distant sites that regained protection of the BBB. Breast
      cancer brain metastases involve both extravascular and intravascular growth of
      tumor cells. These distinct pathways contribute to different pathological
      phenotypes that generate a heterogeneous BBB that facilitates or inhibits the
      delivery of chemotherapeutic drugs to the tumor.

PMID- 17187363
TI  - The p53 positive Bcl-2 negative phenotype is an independent marker of prognosis
      in breast cancer.
AB  - The purpose of this work was to determine if the immunohistochemical p53 (+) Bcl
      2 (-) phenotype predicts survival in breast cancer patients. Tissue from 819
      cases of resected primary breast cancer, presented between 1986 and 1998, were
      assembled in tissue microarray format. Clinicopathological data and prospective
      disease specific survival data were collected prospectively and
      immunohistochemical analyses of p53 and Bcl-2 expression were performed using
      antibodies DO-7 (p53) and 124 (Bcl-2) employing a standard IHC protocol. The
      expression data were correlated with clinicopathological variables and outcomes
      in both univariate (chi(2)) and multivariate (Cox's regression) analyses.
      Abnormal p53 expression and positive Bcl-2 expression were detected in 29%
      (193/673) and 46% (307/673) of tumours, respectively. On univariate analysis Bcl
      2 expression was correlated with the clinicopathological features of less
      aggressive disease and loss of Bcl-2 expression correlated with a reduction in
      survival (log rank = 11.91; p < 0.001). p53 expression correlated with the
      clinicopathological features of aggressive cancers and a reduction in survival
      (log rank = 17.81; p < 0.001). Nineteen percent (127/673) of tumours displayed a
      p53 (+) Bcl-2 (-) phenotype. Kaplan-Meier analysis revealed a significant
      reduction in survival in these cases (log rank 34.01; p < 0.001). Multivariate
      analysis showed that while neither p53 expression nor Bcl-2 expression alone had
      independent prognostic significance, the p53 (+) Bcl-2 (-) phenotype remained
      independently associated with a worse prognosis (HR 1.79 95%CI 1.10-2.89 p =
      0.018).

PMID- 17187364
TI  - The hepatitis B virus X protein promotes hepatocellular carcinoma metastasis by
      upregulation of matrix metalloproteinases.
AB  - The hepatitis B virus (HBV) is a major cause of human hepatocellular carcinoma
      (HCC) which has a very high mortality rate due to high incidence of metastasis.
      It is unknown whether HBV contributes to HCC metastasis. In this report, we
      present clinical data obtained from HCC patients indicating that the expression
      of hepatitis B virus X protein (HBx) in HCC is associated with an increased
      expression of membrane-type 1 matrix metalloproteinase (MT1-MMP), and matrix
      metalloproteinase-2(MMP-2), which correlates with a poor prognosis. We further
      demonstrate experimentally that HBx upregulates MT1-MMP, which in turn induces
      MMP-2. Significantly, HBx-mediated MMP activation is associated with a marked
      increase of cell migration, as revealed by both wound-healing and transwell
      migration assays, suggesting that HBx may facilitate tumor cell invasion by
      upregulation of MMPs and subsequent destruction of the extracellular matrix.
      Together, our results support a model in which HBx contributes to HCC metastasis
      by upregulation of MMPs.

PMID- 17187365
TI  - Risk for breast cancer among women with endometriosis.
AB  - Although several risk factors are common to endometriosis and breast cancer, the
      results of observational studies of an association have so far been inconsistent.
      We evaluated the relationship between endometriosis and breast cancer on the
      basis of data on selected cancers and medical histories from the Danish
      nationwide cancer and hospital registries used in a large case-cohort study. A
      total of 114,327 women were included in the study of whom 1,978 women had
      received a diagnosis of endometriosis and 16,983 had had a diagnosis of breast
      cancer between 1978 and 1998. Of the women with endometriosis, 236 subsequently
      received a diagnosis of breast cancer. The crude overall rate ratio for breast
      cancer after endometriosis was 1.00 and after adjustment for reproductive
      factors, calendar-period, bilateral oophorectomy and benign breast disease, the
      rate ratio was 0.97 (95% confidence interval, 0.85-1.11). The risk for breast
      cancer increased with age at diagnosis of endometriosis, so that women in whom
      endometriosis was diagnosed at a young age (approximately <40 years) had a
      reduced risk for breast cancer and women in whom endometriosis was diagnosed at
      older ages (approximately > or =40 years) tended to have an increased risk for
      breast cancer. The reduced risks observed among young women may reflect their
      exposure to drugs with antiestrogenic effects. The increased risk associated with
      endometriosis among postmenopausal women may be due to common risk factors
      between postmenopausal endometriosis and breast cancer or an altered endogenous
      estrogen.

PMID- 17187367
TI  - Photoreceptor proteins as cancer-retina antigens.
AB  - Melanocytes, melanoma and photoreceptor cells are of neuroectodermal origin and
      have a certain sensitivity to light. In this study, we present evidence for
      photoreceptor proteins that are responsible for visual transduction and its
      regulation function as a new class of cancer antigens in melanoma. Visual
      rhodopsin, transducin, cGMP-phosphodiesterase 6, cGMP-dependent channels,
      guanylyl cyclase, rhodopsin kinase, recoverin and arrestin are expressed in
      melanoma and can induce antibody responses in patients. Melanocytes also express
      mRNA of all photoreceptor genes besides transducin, but were devoid of the
      corresponding protein, which was tested for rhodopsin, cGMP-phosphodiesterase,
      guanylyl cyclase and recoverin. Furthermore, we show for the first time that some
      healthy tissues express mRNA of these genes, but never protein. Expression
      profiles and autoantibody responses were confirmed in the MT/ret and the
      HGF(tg)/Ink4a(-/-) transgenic mouse melanoma models. We propose a molecular
      transition of cancer-retina antigens from mRNA expression in melanocytes to
      protein expression in melanoma. Our work provides the basis for analyzing
      regulation of photoreceptor gene expression in normal and malignant cells as well
      as possible therapeutic tumor targeting using the newly defined class of cancer
      retina antigens.

PMID- 17187366
TI  - Competitive inhibition of carcinogen-activating CYP1A1 and CYP1B1 enzymes by a
      standardized complex mixture of PAH extracted from coal tar.
AB  - A complex mixture of polycyclic aromatic hydrocarbons (PAH) extracted from coal
      tar, the Standard Reference Material (SRM) 1597, was recently shown to decrease
      the levels of DNA binding of the 2 strong carcinogens benzo[a]pyrene (BP) and
      dibenzo[a,l]pyrene (DBP) in the human mammary carcinoma-derived cell line MCF-7
      (Mahadevan et al., Chem Res Toxicol 2005;18:224-231). The present study was
      designed to further elucidate the biochemical mechanisms involved in this
      inhibition process. We examined the effects of SRM 1597 on the metabolic
      activation of BP and DBP toward DNA-binding derivatives in Chinese hamster cells
      expressing either human cytochrome P450 (CYP) 1A1 or CYP1B1. SRM 1597 inhibited
      BP-DNA adduct formation through the entire exposure time in cells expressing
      human CYP1A1, while it significantly inhibited adduct formation only up to 48 hr
      when co-treated with DBP. Conversely, human CYP1B1-expressing cells were unable
      to catalyze PAH-DNA adduct formation on treatment with SRM 1597 alone, and on co
      treatment with BP or DBP. The data obtained from biochemical experiments revealed
      that SRM 1597 competitively inhibited the activity of both human enzymes as
      analyzed by 7-ethoxyresorufin O-deethylation assays. While the Michaelis-Menten
      constant (K(M)) was <0.4 microM in the absence of SRM 1597, this value increased
      up to 1.12 (CYP1A1) or 4.45 microM (CYP1B1) in the presence of 0.1 microg/ml SRM
      1597. Hence the inhibitory effects of the complex mixture on human CYP1B1 were
      much stronger when compared to human CYP1A1. Taken together, the decreases in PAH
      DNA adduct formation on co-treatment with SRM 1597 revealed inhibitory effects on
      the CYP enzymes that convert carcinogenic PAH into DNA-binding metabolites. The
      implications for the tumorigenicity of complex environmental PAH mixtures are
      discussed.

PMID- 17187369
TI  - Dietary acrylamide and renal cell cancer.

PMID- 17187368
TI  - Critical role for matrix metalloproteinase-9 in platelet-activating factor
      induced experimental tumor metastasis.
AB  - In this study, the roles of matrix metalloproteinase (MMP)-2 and MMP-9 in
      platelet-activating factor (PAF)-induced experimental pulmonary metastasis of the
      murine melanoma cell, B16F10, were investigated. An injection of PAF resulted in
      increases in mRNA expression, protein levels and the activities of both MMP-2 and
      MMP-9 in the lungs. The overall expression of MMP-9 was stronger than that of MMP
      2. The increased MMP-9 expression was inhibited by both NF-kappaB and AP-1
      inhibitors, whereas the increased MMP-2 expression was inhibited by only AP-1
      inhibitors. Immunohistochemical analysis revealed that MMP-9 was expressed in
      bronchial epithelial cells as well as in the walls of blood vessels, whereas MMP
      2 expression was observed only in bronchial epithelial cells. PAF significantly
      enhanced the pulmonary metastasis of B16F10, which was inhibited by both NF
      kappaB and c-jun inhibitors. MMP-9 inhibitor, but not that of MMP-2, completely
      inhibited PAF-induced B16F10 metastasis. These data indicate that MMP-9, the
      expression of which was regulated by NF-kappaB and AP-1, plays a critical role in
      PAF-induced enhancement of pulmonary melanoma metastasis.

PMID- 17187370
TI  - Investigation of downstream target genes of PAX3c, PAX3e and PAX3g isoforms in
      melanocytes by microarray analysis.
AB  - PAX3 encodes a transcription factor, which with Zic1 is necessary for induction
      of the neural crest during early embryonic development. There are 7 human PAX3
      isoforms (a-h). PAX3e is the full length isoform comprising 10 exons. PAX3c
      comprises 8 exons plus 5 codons of intron 8, while PAX3g has a truncated
      transactivation domain. Previous studies by us indicated that these isoforms have
      different activities in melanocytes in vitro. In this study, a mouse gene oligo
      array ( approximately 7.5 k oligos), from the Human Genome Mapping Project (HGMP)
      Resource Centre, was used to screen for alterations in downstream gene expression
      in PAX3c, PAX3e and PAX3g melanocyte transfectants, compared with empty vector
      controls. The data analyses identified 109 genes up or downregulated, at least 2
      fold, and involved in cell differentiation, proliferation, migration, adhesion,
      apoptosis and angiogenesis. Semi-quantitative RT-PCR and Western blotting
      confirmed the changes identified by microarrays for several putative targets of
      PAX3, including Met, MyoD and Muc18, and previously undescribed targets,
      including Dhh, Fgf17, Kitl and Rac1. Thus, our data reveal that PAX3 isoforms
      regulate distinct but overlapping sets of genes in melanocytes in vitro.

PMID- 17187372
TI  - New insights into the nucleophosmin/nucleoplasmin family of nuclear chaperones.
AB  - Basic proteins and nucleic acids are assembled into complexes in a reaction that
      must be facilitated by nuclear chaperones in order to prevent protein aggregation
      and formation of non-specific nucleoprotein complexes. The
      nucleophosmin/nucleoplasmin (NPM) family of chaperones [NPM1 (nucleophosmin),
      NPM2 (nucleoplasmin) and NPM3] have diverse functions in the cell and are
      ubiquitously represented throughout the animal kingdom. The importance of this
      family in cellular processes such as chromatin remodeling, genome stability,
      ribosome biogenesis, DNA duplication and transcriptional regulation has led to
      the rapid growth of information available on their structure and function. The
      present review covers different aspects related to the structure, evolution and
      function of the NPM family. Emphasis is placed on the long-term evolutionary
      mechanisms leading to the functional diversification of the family members, their
      role as chaperones (particularly as it pertains to their ability to aid in the
      reprogramming of chromatin), and the importance of NPM2 as an essential component
      of the amphibian chromatin remodeling machinery during fertilization and early
      embryonic development.

PMID- 17187373
TI  - Nemaline myopathy caused by absence of alpha-skeletal muscle actin.
AB  - OBJECTIVE: To investigate seven congenital myopathy patients from six families:
      one French Gypsy, one Spanish Gypsy, four British Pakistanis, and one British
      Indian. Three patients required mechanical ventilation from birth, five died
      before 22 months, one is ventilator-dependent, but one, at 30 months, is sitting
      with minimal support. All parents were unaffected. METHODS: The alpha-skeletal
      muscle actin gene (ACTA1) was sequenced. Available muscle biopsies were
      investigated by standard histological and electron microscopic techniques. The
      expression of various proteins was determined by immunohistochemistry, western
      blotting, or both. RESULTS: Three homozygous ACTA1 null mutations were
      identified: p.Arg41X in the French patient, p.Tyr364fsX in the Spanish patient,
      and p.Asp181fsX10 in all five British patients. An absence of alpha-skeletal
      muscle actin protein but presence of alpha-cardiac actin was shown in all muscle
      biopsies examined, with more alpha-cardiac actin in the biopsy from the child
      with the greatest muscle function. Muscle biopsies from all patients exhibited
      nemaline bodies whereas three also contained zebra bodies. INTERPRETATION: The
      seven patients have recessive nemaline myopathy caused by absence of alpha
      skeletal muscle actin. The level of retention of alpha-cardiac actin, the
      skeletal muscle fetal actin isoform, may determine alpha-skeletal muscle actin
      disease severity. This has implications for possible future therapy.

PMID- 17187371
TI  - Ectoplasmic specialization: a friend or a foe of spermatogenesis?
AB  - The ectoplasmic specialization (ES) is a testis-specific, actin-based hybrid
      anchoring and tight junction. It is confined to the interface between Sertoli
      cells at the blood-testis barrier, known as the basal ES, as well as between
      Sertoli cells and developing spermatids designated the apical ES. The ES shares
      features of adherens junctions, tight junctions and focal contacts. By adopting
      the best features of each junction type, this hybrid nature of ES facilitates the
      extensive junction-restructuring events in the seminiferous epithelium during
      spermatogenesis. For instance, the alpha6beta1-integrin-laminin 333 complex,
      which is usually limited to the cell-matrix interface in other epithelia to
      facilitate cell movement, is a putative apical ES constituent. Furthermore, JAM-C
      and CAR, two tight junction integral membrane proteins, are also components of
      apical ES involving in spermatid orientation. We discuss herein the mechanisms
      that maintain the cross-talk between ES and blood-testis barrier to facilitate
      cell movement and orientation in the seminiferous epithelium.

PMID- 17187374
TI  - Neural precursors attenuate autoimmune encephalomyelitis by peripheral
      immunosuppression.
AB  - OBJECTIVE: Intracerebroventricular or intravenous (IV) injection of neural
      precursor cells (NPCs) attenuates experimental autoimmune encephalomyelitis
      (EAE), the animal model of multiple sclerosis. Although stem cell therapy was
      introduced initially for cell replacement, we examine here whether NPCs possess
      immunomodulatory effects. METHODS: We examined the effects of systemic
      administration of NPCs on central nervous system (CNS) inflammation in EAE and
      the interactions between NPCs and T cells in vitro and in vivo. RESULTS: IV NPC
      therapy decreased significantly CNS inflammation and tissue injury and attenuated
      the clinical severity of EAE. IV-injected NPCs could not be found in the CNS but
      were detected in lymphoid organs. Coculture experiments showed that NPCs
      inhibited the activation and proliferation of lymph node-derived T cells in
      response to CNS-derived antigens and to nonspecific polyclonal stimuli. The
      relevance of NPC/lymph node cell interactions in vivo was further demonstrated
      when lymph node cells obtained from IV NPC-treated mice exhibited poor
      encephalitogenicity on transfer to naive mice and caused a markedly milder EAE
      compared with those obtained from nontreated mice. INTERPRETATION: IV
      administration of neural precursors inhibits EAE by a peripheral
      immunosuppressive effect. Our findings suggest a profound bystander inhibitory
      effect of NPCs on T-cell activation and proliferation in the lymph nodes, leading
      to amelioration of EAE.

PMID- 17187376
TI  - The trick of the tail: protein-protein interactions of metabotropic glutamate
      receptors.
AB  - It was initially believed that G-protein-coupled receptors, such as metabotropic
      glutamate receptors, could simply be described as individual proteins that are
      associated with intracellular signal cascades via G-proteins. This view is no
      longer tenable. Today we know that metabotropic glutamate receptors (mGluRs) can
      dimerize and bind to a variety of proteins in addition to trimeric G-proteins.
      These newly identified protein interactions led to the discovery of new
      regulatory mechanisms that are independent of and sometimes synergistic with the
      classical G-protein-coupled second messenger pathways. Notably, several of these
      mechanisms connect mGluR-mediated signaling to other receptor classes, thereby
      creating a network of different receptor types and associated signal cascades.
      The intracellular C-termini of mGluRs play a key role in the regulation of these
      networks, and various new protein interactions of these domains were described
      recently. Because mGluRs are involved in a variety of physiological and
      pathophysiological processes, some of the proteins interacting with this receptor
      class have potential as valuable pharmaceutical targets. This review will give a
      comprehensive overview of proteins interacting with mGluR C-termini, highlight
      new evolving regulatory mechanisms for glutamatergic signal transduction and
      discuss possibilities for future drug development.

PMID- 17187375
TI  - Heterozygous parkin point mutations are as common in control subjects as in
      Parkinson's patients.
AB  - OBJECTIVE: Homozygous or compound heterozygous parkin mutations cause juvenile
      parkinsonism. Heterozygous parkin mutations are also found in patients with
      typical Parkinson's disease (PD), but it is unclear whether a single "mutation"
      in a patient is related to disease or is coincidental, because the mutation
      frequency in control subjects is unknown. We present a comprehensive sequence
      analysis of parkin in control subjects. METHODS: A total of 302 patients and 301
      control subjects were sequenced, and findings were replicated in 1,260 additional
      patients and 1,657 control subjects. RESULTS: Thirty-four variants were detected,
      of which 21 were novel; 12 were polymorphisms and 22 were rare variants. Patients
      and control subjects did not differ in the frequency, type, or functional
      location of the variants. Even P437L, a common mutation thought to be pathogenic,
      was present in unaffected control subjects. INTERPRETATION: parkin point
      mutations are not exclusive to PD. The mere presence of a single point mutation
      in a patient, in the absence of a second mutation, should not be taken as a cause
      of disease unless corroborated by family data and functional studies. This study
      does not support the notion that heterozygous parkin sequence variants (mutations
      or polymorphisms) are risk factors for PD. Whether heterozygous dosage anomalies
      are associated with PD remains to be determined.

PMID- 17187377
TI  - Human brain structural change related to acute single exposure to sarin.
AB  - OBJECTIVE: This study aimed to identify persistent morphological changes
      subsequent to an acute single-time exposure to sarin, a highly poisonous
      organophosphate, and the neurobiological basis of long-lasting somatic and
      cognitive symptoms in victims exposed to sarin. METHODS: Thirty-eight victims of
      the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency
      department for sarin intoxication, and 76 matched healthy control subjects
      underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in
      2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and
      longitudinally after the exposure and the current severity of chronic reports in
      the victims were also evaluated. RESULTS: The voxel-based morphometry exhibited
      smaller than normal regional brain volumes in the insular cortex and neighboring
      white matter, as well as in the hippocampus in the victims. The reduced regional
      white matter volume correlated with decreased serum cholinesterase levels and
      with the severity of chronic somatic complaints related to interoceptive
      awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging
      further demonstrated an extensively lower than normal fractional anisotropy in
      the victims. All these findings were statistically significant (corrected p <
      0.05). INTERPRETATION: Sarin intoxication might be associated with structural
      changes in specific regions of the human brain, including those surrounding the
      insular cortex, which might be related to elevated subjective awareness of
      internal bodily status in exposed individuals.

PMID- 17187378
TI  - Coupled positive and negative feedback circuits form an essential building block
      of cellular signaling pathways.
AB  - Cellular circuits have positive and negative feedback loops that allow them to
      respond properly to noisy external stimuli. It is intriguing that such feedback
      loops exist in many cases in a particular form of coupled positive and negative
      feedback loops with different time delays. As a result of our mathematical
      simulations and investigations into various experimental evidences, we found that
      such coupled feedback circuits can rapidly turn on a reaction to a proper
      stimulus, robustly maintain its status, and immediately turn off the reaction
      when the stimulus disappears. In other words, coupled feedback loops enable
      cellular systems to produce perfect responses to noisy stimuli with respect to
      signal duration and amplitude. This suggests that coupled positive and negative
      feedback loops form essential signal transduction motifs in cellular signaling
      systems.

PMID- 17187379
TI  - Peopling of South Asia: investigating the caste-tribe continuum in India.
AB  - In recent years, mtDNA and Y chromosome studies involving human populations from
      South Asia and the rest of the world have revealed new insights about the
      peopling of the world by anatomically modern humans during the late Pleistocene,
      some 40,000-60,000 years ago, over the southern coastal route from Africa.
      Molecular studies and archaeological record are both largely consistent with
      autochthonous differentiation of the genetic structure of the caste and tribal
      populations in South Asia. High level of endogamy created by numerous social
      boundaries within and between castes and tribes, along with the influence of
      several evolutionary forces such as genetic drift, fragmentation and long-term
      isolation, has kept the Indian populations diverse and distant from each other as
      well as from other continental populations. This review attempts to summarize
      recent genetic studies on Indian caste and tribal populations with the focus on
      the information embedded in the socially defined structure of Indian populations.

PMID- 17187380
TI  - Employer costs of alcohol-involved injuries.
AB  - BACKGROUND: This study estimates the annual cost of alcohol-related injuries to
      employers in 1998-2000. METHODS: Incidence was estimated with occupational injury
      data, motor vehicle crash data and health care data for 1998-2000. Employer costs
      were estimated from federal estimates of injury costs by source of payment using
      data on the percentage of varied payment streams (e.g., health insurance, sick
      leave) paid by employers. RESULTS: The annual employer cost of alcohol-related
      injuries to employees and their dependents exceed US dollars 28.6 billion. Out of
      this, US dollars 13.2 billion comes from job-related, alcohol-involved injuries.
      The annual employer cost of motor vehicle crashes in which at least one driver
      was alcohol-impaired is over US dollars 9.2 billion. Out of this, only US dollars
      3.4 billion comes from job-related alcohol involvement. CONCLUSION: Safety
      programs can reduce the fringe benefit bill without reducing the benefits offered
      to employees.

PMID- 17187381
TI  - Categorizing nasal septal perforations of occupational origin as cases of
      corrosive rhinitis.
AB  - BACKGROUND: In clinical practice a perforation of the nasal septum secondary to
      an occupational exposure to corrosive chemicals is not considered a sequel of
      rhinitis. METHODS: Relevant articles published in the last 26 years were searched
      and retrieved from PubMed. RESULTS: Patients with nasal septal perforations of
      occupational origin show a history of rhinitis with a gradual installation of
      symptoms and damage of the nasal mucosa progressing to ulceration and ultimately
      to perforation of the nasal septum. CONCLUSION: Patients with nasal septal
      perforations of occupational origin exhibit the clinical and histopathological
      features of rhinitis whereby they should be categorized as rhinitics. This
      rhinitis should be considered as a type of irritant-induced occupational rhinitis
      and classified as corrosive rhinitis.

PMID- 17187382
TI  - A rebuttal: secret ties to industry and conflicting interests in cancer research.

PMID- 17187383
TI  - Developmental toxic effects of antifungal flusilazole administered by gavage to
      mice.
AB  - BACKGROUND: The developmental toxicity of flusilazole was studied in CD-1 mice
      after oral administration. METHODS: Pregnant mice were given flusilazole at doses
      of 0 (corn oil), 10, 20, and 40 mg/kg/day, by gavage, on gestational days (GD) 6
      15. RESULTS: Maternal toxicity, as evidenced by reduction in body weight gain and
      signs of toxicity, was observed at the middle- and high-dose groups. No
      significant incidence of resorptions or death was observed in any of dose groups.
      There was a pronounced reduction in fetal weight, which was significantly lower
      than control from 20 and 40 mg/kg/day. There was no significant increase in the
      incidence of fetuses with external or visceral malformations in any of dose
      groups, but there was a significant increase in the incidence of skeletal
      malformations was observed at 20 and 40 mg/kg/day. CONCLUSIONS: The results of
      this study reported marked maternal toxicity, growth retardation, and skeletal
      abnormalities in the mid- and high-dose groups. It seems likely that marked
      maternal toxicity contributed to the observed alterations in fetal growth
      retardation and skeletal development. The no-observed-effect level in the present
      study for maternal and developmental toxicity was 10 mg/kg/day.

PMID- 17187384
TI  - Biofilm formation by Propionibacterium acnes on biomaterials in vitro and in
      vivo: impact on diagnosis and treatment.
AB  - Propionibacterium acnes is found increasingly as a cause of delayed infection,
      usually involving implanted biomaterials. Despite susceptibility to common
      antibiotics, such infections are very difficult to treat and usually require
      surgical removal of the device. Three clinical isolates of P. acnes were assessed
      for ability to adhere to titanium, surgical steel and silicone, with and without
      a plasma conditioning film. After adherence, the biomaterials were then incubated
      for a further 6 days and examined for biofilm development. All three isolates
      adhered to all three biomaterials similarly. Importantly, we were able to
      demonstrate biofilm formation, including production of exopolymer similar in
      appearance to the polysaccharide intercellular adhesin of Staphylococcus
      epidermidis. A case summary also demonstrated failure to eradicate P. acnes
      infection in a hydrocephalus shunt after prolonged treatment. The removed shunt
      showed obvious biofilm formation, initially obscured by exopolymer when viewed by
      environmental scanning electron microscopy. Biofilm development by P. acnes
      explains the difficulties encountered in clinical management of such infections.

PMID- 17187386
TI  - PLGA nanometer surface features manipulate fibronectin interactions for improved
      vascular cell adhesion.
AB  - The largest cause of mortality in the Western world is atherosclerotic vascular
      disease. Many of these diseases require synthetic vascular grafts; however, their
      patency rate is only 30% in small (<6 mm) diameter vascular grafts after 5 years
      of implantation. In an effort to increase small diameter vascular graft success,
      researchers have been designing random nanostructured surface features which
      enhance vascular cell functions. However, for the present study, highly
      controllable, nanostructured features on poly(lactic-co-glycolic acid) (PLGA)
      surfaces were formulated. To create ordered nanostructured roughness on PLGA
      surfaces, either 500, 200, or 100 nm polystyrene nanospheres were separately
      placed onto mica. These were then used as a template for creating an inverse
      poly(dimethylsiloxane) mold which was utilized to cast PLGA. Compared to all
      other PLGA films formulated, AFM results demonstrated greater initial fibronectin
      spreading on PLGA which possessed spherical 200 nm features. Compared to smooth
      PLGA, PLGA with 500 or 100 nm surface features, results further showed that PLGA
      with 200 nm spherical features promoted vascular cell (specifically, endothelial,
      and smooth muscle cell) adhesion. In this manner, the present study demonstrated
      a specific nanometer surface feature size that promoted fibronectin spreading and
      subsequent vascular cell adhesion; criteria critical to vascular graft success.

PMID- 17187385
TI  - Evaluation of the biological responses of osteoblast-like UMR-106 cells to the
      engineered porous PHBV matrix.
AB  - Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) has been investigated for
      biomedical applications due to its many biologically favorable properties.
      However, to explore its application in bone tissue engineering, the poorly
      bioactive surface property of PHBV must be improved. To engineer PHBV to achieve
      a biologically active surface, in this study each porous PHBV matrix was prepared
      by solute leaching of salt/PHBV cast film and was treated with ozone followed by
      dip coating with type I collagen. The biological responses of osteoblast-like UMR
      106 cells after being grown on the engineered PHBV matrix were evaluated.
      Confocal microscopy and the MTT assay were used to map and quantify the viable
      cell proliferation on the PHBV matrix, respectively. The cells were cultivated in
      osteogenic media containing beta-glycerophosphate and later stained with alizarin
      red to visualize mineralization of the matrix. RNA was extracted from the UMR-106
      cells, and reverse transcriptase-polymerase chain reaction (RT-PCR) was applied
      to detect expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) (a house
      keeping gene) and bone sialoprotein (BSP) (marker of the osteoblastic phenotype).
      The results showed that the UMR-106 cells after cultivation on the engineered
      PHBV matrix retained the osteoblastic phenotype characteristics, indicating that
      the porous PHBV matrix after ozone treatment and collagen dip coatings are a
      promising scaffold for bone tissue engineering applications.

PMID- 17187387
TI  - Layer-by-layer assembly of biomacromolecules on poly(ethylene terephthalate)
      films and fiber fabrics to promote endothelial cell growth.
AB  - Poly(ethylene terephthalate) (PET) film and PET vascular graft were modified by
      layer-by-layer (LBL) assembly of collagen and chondroitin sulfate (CS) to mimic
      the natural composition and structure of extracellular matrix. PET materials were
      first hydrolyzed to endow the surfaces with negative charge. Alternative assembly
      of positively charged collagen and negatively charged CS was then conducted in an
      LBL manner to produce biological multilayers. X-ray photoelectron spectroscopy
      confirmed the occurrence of hydrolysis and existence of collagen and CS. The
      stepwise layer growth on the PET film was monitored by UV-vis spectroscopy. The
      multilayers had sufficient stability to pass through the cell culture period (8
      days). In vitro endothelial cell culture revealed that the incorporated
      biomacromolecules could significantly improve the cell attachment, proliferation,
      and viability. Cells showed more spreading morphology with preserved phenotype,
      as illustrated by scanning electron microscopy and factor VIII-related antigen
      immunocytochemistry, respectively.

PMID- 17187388
TI  - First trimester exposure to paroxetine and risk of cardiac malformations in
      infants: the importance of dosage.
AB  - BACKGROUND: Conflicting findings with regard to the teratogenic risks of first
      trimester use of paroxetine have prompted the FDA, Health Canada, and the
      manufacturer of the drug to issue warnings against its use during pregnancy.
      Given that untreated depression during pregnancy can lead to deleterious effect
      on the mother and her unborn fetus, data on the relationship between the dose and
      the range of malformations is warranted. This study attempts to quantify the
      association between first trimester exposure to paroxetine and congenital cardiac
      malformations, adjusting for possible confounders, and to quantify the dose
      response relationship between paroxetine use and cardiac defects. METHODS: The
      Medication and Pregnancy registry was used. This population-based registry was
      built by linking three administrative databases (RAMQ, Med-Echo, and ISQ), and
      includes all pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of
      entry in the registry is the date of the first day of the last menstrual period.
      To be eligible for this study, women had to: 1) be 15-45 years of age at entry;
      2) be covered by the RAMQ drug plan >or=12 months before and during pregnancy; 3)
      be using only one type of antidepressant during the first trimester; and 4) have
      a live birth. Two nested case-control studies were carried out comparing the
      prevalence of paroxetine use in the first trimester of pregnancy to the
      prevalence of other antidepressant exposures during the same time period. Cases
      were defined as: 1) any major malformations; or 2) any cardiac malformations
      diagnosed in the first year of life; controls were defined as no major or minor
      malformations. Multivariate logistic regression techniques were used to analyze
      data. RESULTS: Among the 1,403 women meeting inclusion criteria, 101 infants with
      major congenital malformations were identified; 24 had cardiac malformations.
      Adjusting for possible confounders, the use of paroxetine (odds ratio [OR] =
      1.38, 95% confidence interval [CI] = 0.49-3.92), and the use of other SSRIs (OR =
      0.89, 95% CI = 0.28-2.84) during the first trimester of pregnancy did not
      increase the risk of congenital cardiac malformations compared with the use of
      non-SSRI antidepressants. When considering the dose, however, a dose-response
      relationship was observed, thus women exposed to >25 mg/day of paroxetine during
      the first trimester of pregnancy were at increased risk of having an infant with
      major congenital malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17),
      or major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42). CONCLUSIONS:
      Gestational exposure to paroxetine is associated with major congenital
      malformations and major cardiac malformations for only first trimester exposure
      above 25 mg/day.

PMID- 17187389
TI  - Antifungal triazole derivative triadimefon induces ectopic maxillary cartilage by
      altering the morphogenesis of the first branchial arch.
AB  - BACKGROUND: The triazole derivative, triadimefon (FON), induces branchial arch
      abnormalities in post-implantation rat embryos cultured in vitro, and cranio
      facial malformations in mouse fetuses. Ectopic maxillary cartilage has been also
      described as a typical FON-related malformation. This work studies the
      morphogenesis of the ectopic cartilage in rat embryos and fetuses exposed in vivo
      to FON during the early postimplantation period. METHODS: Pregnant rats were
      treated with 0, 250, and 500 mg/kg FON on Day 9.5 of pregnancy (D9.5) and
      sacrificed at term (D20), during the early fetal period (D17) or at different
      embryogenetic periods (D10, D11, D12). The skeleton was examined after stain of
      bone and cartilage or of cartilage alone respectively at term or at D17. The
      neural crest cell (NCC) migration and compaction was investigated at D10 and D11
      and the cranial nerve organization described at D12. RESULTS: Triadimefon is
      teratogenic in rats under the chosen experimental conditions. The malformations
      were at the level of the cranio-facial and axial skeleton at term and of the
      hindbrain nerves in embryos. A NCC abnormal migration and compaction was observed
      at the level of the first branchial arch: in FON-exposed embryos NCC were
      detected at the level of both maxillary and mandibular processes, whereas control
      embryos showed the immunostained tissue only at the level of the mandibular bud.
      CONCLUSIONS: The pathogenic pathway, proposed to explain the ectopic cartilage,
      is the displacement of part of the NCC-derived tissues at the maxillary region of
      the first branchial arch.

PMID- 17187390
TI  - Combustion synthesis of porous biomaterials.
AB  - This article discusses the unique material manufacturing process of self
      propagating high temperature synthesis (SHS) as applied to the making of porous
      biomaterials. Porous materials have long been considered as the first step toward
      in-vivo bone tissue engineering and the creation of patient life-time implants.
      The authors have approached this challenge by utilizing combustion synthesis, to
      create novel materials such as NiTi + TiC as well as porous forms of materials
      that are commonly accepted for biomedical applications such as tricalcium
      phosphate and hydroxyapatite. In the SHS product, physico-chemical properties are
      controlled by, but not limited to, reactant stoichiometry; green density;
      particle size of the reactant mix; use or presence of a gasifying agent; heating
      rate of the reactants and gravity. By balancing these parameters, the energy of
      the reaction is controlled to create the desired product stoichiometry, porosity,
      and mechanical properties. SHS provides a means to rapidly manufacture materials,
      saving time and production costs as well as enabling the synthesis of custom
      devices through the use of individual molds. Mold materials can range from
      graphite to paper or paper machete. Combustion synthesis offers a method for the
      rapid manufacture of affordable, individual biomedical devices that will reduce
      patient recovery time.

PMID- 17187391
TI  - Development of wollastonite-poly(ethylmethacrylate co-vinylpyrrolidone) based
      materials for multifunctional devices.
AB  - The manufacturing of a composite made of a synthetic bioactive ceramic,
      pseudowollastonite (psW), and a bioresorbable copolymer ethylmethacrylate
      vinylpyrrolidone (EMA/VP) is presented in this article. psW porous blocks were
      produced by dipping an open porous polyurethane foam in a psW containing slurry.
      A 40/60 wt % EMA/VP monomers mixture was poured on the blocks, and free radical
      polymerization initiated by azobis(isobutyronitrile) at 50 degrees C. Disks of 1
      mm height were obtained by cutting the composite with a diamond saw, and
      bioresorption and bioactivity of the specimens were tested by immersion of the
      disks into SBF. A ceramic/polymer weight ratio of 72/28, greater than the usually
      achievable ratio by polymeric solidification of slurries of monomers charged with
      a powdered solid component, has been obtained. The system is bioactive and does
      not change the pH of the medium during the degradation test.

PMID- 17187392
TI  - Biofilm formation by Staphylococcus epidermidis on nitrogen ion implanted CoCrMo
      alloy material.
AB  - Staphylococcus epidermidis is the primary cause of medical device-related
      infections due to its adhesion and biofilm forming abilities on biomaterial
      surfaces. For this reason development of new materials and surfaces to prevent
      bacterial adhesion is inevitable. In this study, the adhesion of biofilm forming
      S. epidermidis strain YT-169a on nitrogen (N) ion implanted as well as on as
      polished CoCrMo alloy materials were investigated. A medical grade CoCrMo alloy
      was ion implanted with 60 keV N ions to a high dose of 1.9 x 10(18) ions/cm(2) at
      substrate temperatures of 200 and 400 degrees C. The near-surface implanted layer
      crystal structures, implanted layer thicknesses, and roughnesses were
      characterized by XRD, SEM and AFM. The number of adherent bacteria on the
      surfaces of N implanted specimens was found to be 191 x 10(6) CFU/cm(2) for the
      200 degrees C and 70 x 10(6) CFU/cm(2) for the 400 degrees C specimens compared
      to the as-polished specimen (3 x 10(6) CFU/cm(2)). The adhesion test results
      showed that S. epidermidis strain YT-169a adhere much more efficiently to the N
      implanted surfaces than to the as-polished CoCrMo alloy surface. This was
      attributed mainly to the rougher surfaces associated with the N implanted
      specimens in comparison with the relatively smooth surface of the as-polished
      specimen.

PMID- 17187393
TI  - Thermo-responsive poly(NiPAAm-co-DEGMA) substrates for gentle harvest of human
      corneal endothelial cell sheets.
AB  - Gentle harvesting of corneal endothelial cell sheets grown in culture is of
      interest for the development of cornea replacement strategies. Thin films of a
      fast responding copolymer of N-isopropylacrylamide (NiPAAm) and diethyleneglycol
      methacrylate (DEGMA) with a phase transition temperature of 32 degrees C were
      prepared and evaluated for that purpose. The polymer layers were immobilized onto
      fluorocarbon substrates using low pressure argon plasma treatment. Cell culture
      and detachment experiments were performed with L929 mouse fibroblasts and human
      corneal endothelial cells (HCEC) at standard conditions. The hydrogel-coated
      supports were found to permit adhesion, spreading, and proliferation of both cell
      types. Harvesting of cell sheets was achieved upon lowering the temperature to
      about 30 degrees C. The formation of a closed monolayer as a crucial prerequisite
      for maintaining ionic pump function in HCEC was proven by ZO-1 immunostainung.
      Labeling of fibronectin indicated that the vast majority of the extracellular
      matrix is detached from the hydrogel coatings together with the cell layer.
      Inspired by this result, the reuse of the hydrogel-coated culture carriers was
      investigated confirming the suitability of the substrates for repeated cell
      harvesting. Altogether, the introduced thermoresponsive coating was found
      advantageous for the efficient generation of HCEC sheets and will be further
      utilized in transplantation strategies.

PMID- 17187394
TI  - Fatigue-crack growth properties of thin-walled superelastic austenitic Nitinol
      tube for endovascular stents.
AB  - Over the past 10 years, the supereleastic nickel-titanium alloy Nitinol has found
      widespread application in the manufacture of small-scale biomedical devices, such
      as self-expanding endovascular stents. Although conventional stress/strain-life
      (S/N) analyses are invariably used as the primary method for design against
      fatigue loading and for predicting safe lifetimes, fracture mechanics-based
      methodologies provide a vital means of assessing the quantitative effect of
      defects on such lifetimes. Unfortunately, fracture mechanics studies on fatigue
      in Nitinol are scarce, and most results do not pertain to the (thin-walled tube)
      product forms that are typically used in the manufacture of endovascular stents.
      In the current work, we document the basic fatigue-crack growth properties of
      flattened thin-walled ( approximately 400 microm thick) Nitinol tubing in a 37
      degrees C air environment. Crack-growth behavior is characterized over a wide
      range of growth rates ( approximately 6 orders of magnitude) and load ratios,
      that is, as a function of the alternating and maximum stress intensities, at 50
      Hz. Limited experiments at both 5 and 50 Hz were also performed in 37 degrees C
      air and simulated body fluid to determine whether the cyclic frequency affects
      the fatigue behavior. Fatigue-crack growth-rate properties in such thin-walled
      Nitinol tube are found to be quite distinct from limited published data on other
      (mainly bulk) product forms of Nitinol, for example, bar and strip, both in terms
      of the relative fatigue thresholds and the variation in steady-state growth
      rates.

PMID- 17187395
TI  - Enhanced antigen-specific primary CD4+ and CD8+ responses by codelivery of
      ovalbumin and toll-like receptor ligand monophosphoryl lipid A in poly(D,L-lactic
      co-glycolic acid) nanoparticles.
AB  - The purpose of this research was to investigate the use of biodegradable poly(D,L
      lactic-co-glycolic acid) nanoparticles (PLGA-NP) as a vaccine delivery system to
      codeliver antigen, ovalbumin (OVA) along with monophosphoryl lipid A (MPLA) as
      adjuvant for induction of potent CD4(+) and CD8(+) T cell responses. The primary
      CD4(+) T responses to OVA/MPLA NP were investigated using OVA-specific T cells
      from DO11.10 transgenic mice. Following adoptive transfer of these cells, mice
      were immunized s.c. by NP formulations. For assessing the CD8(+) responses, bone
      marrow derived dendritic cells (DCs) were pulsed with different OVA formulations,
      then, cocultured with CD8(+) T cells from OT-1 mice. T cell
      proliferation/activation and IFN-gamma secretion profile have been examined.
      Particulate delivery of OVA and MPLA to the DCs lead to markedly increase in in
      vitro CD8(+) T cell T cell proliferative responses (stimulation index >3000) and
      >13-folds increase in in vivo clonal expanded CD4(+) T cells. The expanded T
      cells were capable of cytokine secretion and expressed an activation and memory
      surface phenotype (CD62L(lo), CD11a(hi), and CD44(hi)). Codelivery of antigen and
      MPLA in PLGA-NP offers an effective method for induction of potent antigen
      specific CD4(+) and CD8(+) T cell responses.

PMID- 17187396
TI  - Expression of sulfotransferase 1E1 in human prostate as studied by in situ
      hybridization and immunocytochemistry.
AB  - BACKGROUND: Estrogen is recognized to play a role in the development and function
      of the prostate. Estrogen sulfotransferase (EST) 1E1 catalyzes the
      sulfoconjugation of estrogen and is thus involved in the metabolism of estrogen.
      We have recently shown that EST 1E1 is highly expressed in male mouse
      reproductive organs, including prostate. It appeared of interest to study the
      expression of EST 1E1 in human prostate. METHODS: EST 1E1 mRNA and protein
      expression was evaluated in benign prostatic hyperplasia (BPH) using in situ
      hybridization and immunocytochemistry, respectively. RESULTS: EST 1E1 mRNA and
      protein were found to be expressed in epithelial cells bordering alveola lumen
      (luminal cells) as well as stroma cells. CONCLUSION: The enzyme EST may play a
      physiological role in regulating local estrogen levels in human prostate.

PMID- 17187397
TI  - Magnetic resonance imaging and histopathological characterization of prostate
      tumors in TRAMP mice as model for pre-clinical trials.
AB  - BACKGROUND: The Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) develops
      progressive forms of prostate cancer. Due to the lack of a validated non-invasive
      methodology, pathology has been so far the most common parameter evaluated in
      efficacy studies. METHODS: We studied by magnetic resonance imaging (MRI) 210
      mice that were repeatedly measured up to 33 weeks of age in order to stage
      prostate tumors and follow pathological progression in single animals. A pre
      clinical trial with doxorubicin was also performed. RESULTS: Progressive forms of
      cancer (well and poorly differentiated (PD) adenocarcinomas) were easily
      recognized on MR images and MRI findings were validated against histopathological
      analysis. Age at tumor onset was different for the two tumoral forms. Doxorubicin
      treatment caused a strong reduction in tumor volume. CONCLUSIONS: Prostate cancer
      in TRAMP mice is multifocal and heterogeneous: a non-invasive methodology such as
      MRI facilitates the rational design of translational pre-clinical trials in this
      widely used animal model.

PMID- 17187398
TI  - The addition of biphasic calcium phosphate to porous chitosan scaffolds enhances
      bone tissue development in vitro.
AB  - Uniform distribution of cells and their extracellular matrix is essential for the
      in vivo success of bone tissue engineering constructs produced in vitro. In this
      study, the effects of biphasic calcium phosphate (BCP) granules embedded into
      chitosan scaffolds on the distribution, morphology, and phenotypic expression of
      osteoblastic cells were investigated. Mesenchymal stem cells (MSCs) and
      preosteoblasts were cultured on chitosan scaffolds with and without BCP under
      osteoblastic differentiation/maturation conditions for periods up to 4 weeks. The
      addition of 25 wt % BCP to chitosan created a uniform layer of calcium phosphate
      (CaP) precipitation similar to bone mineral on the scaffold surfaces as
      determined by scanning electron microscopy and X-ray spectroscopy. Scaffolds with
      this CaP layer yielded more uniform and complete cell and ECM distribution than
      chitosan scaffolds without BCP. The suggestion of chemotaxis in the appearance of
      this response was confirmed by successive experiments in a Boyden chamber. The
      CaP layer also altered morphology of cells initially attached to the scaffold
      surfaces, leading to higher expression of marker proteins of osteoblastic
      phenotype including alkaline phosphatase and osteocalcin. The use of chitosan/BCP
      scaffolds for culture of MSCs and preosteoblasts enhances bone tissue development
      in vitro.

PMID- 17187399
TI  - Fibrinolytic properties of lysine-derivatized polyethylene in contact with
      flowing whole blood (Chandler loop model).
AB  - This article reports on the concept of a fibrinolytic surface based on the
      preferential adsorption of endogenous plasminogen from blood. Data are presented
      indicating that such a surface, when pretreated with tissue-type plasminogen
      activator (tPA), is able to dissolve nascent thrombus generated in contact with
      flowing whole blood. Polyethylene (PE) surfaces were modified by attaching a
      lysine-containing polymer using photochemical methods as reported previously
      (McClung et al., J Biomed Mater Res 2000;49:409-414). The lysine residues were
      bound chemically to the polymer via the alpha-amino groups leaving the epsilon
      amino groups free (epsilon-Lys surface). Control surfaces were (a) unmodified PE,
      (b) PE modified with the coating polymer containing no lysine, and (c) PE
      modified with the polymer containing lysine bound via the epsilon-amino group.
      The materials in tubing form were evaluated in contact with nonanticoagulated
      flowing human whole blood in a modified Chandler Loop experiment. They were first
      treated with tPA to allow activation of adsorbed plasminogen to plasmin. It was
      found that thrombus formation was initiated within 15-25 min (depending on donor
      blood) on all surfaces, as indicated by the formation of platelet aggregates. On
      the controls (including the lysine-containing material in which the epsilon-amino
      group was used in the binding reaction) thrombogenesis continued till the tubing
      was occluded and blood flow ceased. On the epsilon-Lys surface, thrombogenesis
      was interrupted at various stages depending on the donor blood; in all cases any
      thrombus generated was dissolved within minutes. It was shown that thrombolysis
      was due to the fibrinolytic action of plasmin generated at the surface and not to
      plasmin formed by traces of tPA released into the blood. This work provides
      further evidence of the efficacy of this approach to the development of a
      fibrinolytic surface.

PMID- 17187400
TI  - Nanomechanical analysis of bone tissue engineering scaffolds.
AB  - Copolymers of (2-hydroxyethyl methacrylate) (HEMA) and methacrylamide monomers
      conjugated with amino acids were synthesized and crosslinked with ethylene glycol
      dimethacrylate. The resulting library of copolymers was mineralized in vitro
      using two distinct methods. In the first mineralization method, the copolymers
      were polymerized in the presence of a sub-micron hydroxyapatite (HA) suspension.
      In the second method, copolymers were mineralized with HA using a urea-mediated
      process. The mechanical properties of all of the copolymers, both mineralized and
      not, were determined using nanoindentation under both load and displacement
      control. A power law fit to the initial unloading curve was used to determine a
      reduced elastic modulus for each material. Between 30 and 300 indentations were
      performed on each material, and ANOVA analysis was run to determine the
      statistical significance of differences in modulus between samples. Using
      nanoindentation, the 22 different samples had reduced modulus values ranging from
      840 MPa to 4.14 GPa. Aspartic acid-methacrylate (Asp-MA) copolymers were not
      distinguishable from the pHEMA control material. Polymerization in the presence
      of HA created a more uniform material than the urea method of mineralization.
      Several challenges and solutions encountered in the nanomechanical testing of
      soft, heterogeneous materials are discussed. These results demonstrate that with
      proper experimental design, the mechanical properties of tissue engineering
      scaffold materials based on polymer-ceramic composite materials can be determined
      using small samples and nanoindentation techniques.

PMID- 17187401
TI  - Repeated measurement sampling in genetic association analysis with genotyping
      errors.
AB  - Genotype misclassification occurs frequently in human genetic association
      studies. When cases and controls are subject to the same misclassification model,
      Pearson's chi-square test has the correct type I error but may lose power. Most
      current methods adjusting for genotyping errors assume that the misclassification
      model is known a priori or can be assessed by a gold standard instrument. But in
      practical applications, the misclassification probabilities may not be completely
      known or the gold standard method can be too costly to be available. The repeated
      measurement design provides an alternative approach for identifying
      misclassification probabilities. With this design, a proportion of the subjects
      are measured repeatedly (five or more repeats) for the genotypes when the error
      model is completely unknown. We investigate the applications of the repeated
      measurement method in genetic association analysis. Cost-effectiveness study
      shows that if the phenotyping-to-genotyping cost ratio or the misclassification
      rates are relatively large, the repeat sampling can gain power over the regular
      case-control design. We also show that the power gain is not sensitive to the
      genetic model, genetic relative risk and the population high-risk allele
      frequency, all of which are typically important ingredients in association
      studies. An important implication of this result is that whatever the genetic
      factors are, the repeated measurement method can be applied if the genotyping
      errors must be accounted for or the phenotyping cost is high.

PMID- 17187402
TI  - The nexus of iron and inflammation in hepcidin regulation: SMADs, STATs, and
      ECSIT.
AB  - Hereditary hemochromatosis, characterized by iron overload in multiple organs, is
      one of the most common genetic disorders among Caucasians. Hepcidin, which is
      synthesized in the liver, plays important roles in iron overload syndromes. Here,
      we show that a Cre-loxP-mediated liver-specific disruption of SMAD4 results in
      markedly decreased hepcidin expression and accumulation of iron in many organs,
      which is most pronounced in liver, kidney, and pancreas. Transcript levels of
      genes involved in intestinal iron absorption, including Dcytb, DMT1, and
      ferroportin, are significantly elevated in the absence of hepcidin. We
      demonstrate that ectopic overexpression of SMAD4 activates the hepcidin promoter
      and is associated with epigenetic modification of histone H3 to a
      transcriptionally active form. Moreover, transcriptional activation of hepcidin
      is abrogated in SMAD4-deficient hepatocytes in response to iron overload, TGF
      beta, BMP, or IL-6. Our study uncovers a novel role of TGF-beta/SMAD4 in
      regulating hepcidin expression and thus intestinal iron transport and iron
      homeostasis [corrected]

PMID- 17187403
TI  - Porphyria cutanea tarda: a possible role for ascorbic acid.

PMID- 17187404
TI  - Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the
      precore protein.
AB  - Toll-like receptors (TLRs) play a key role in the innate immune response. The aim
      of this study was to examine the expression of TLR2 and TLR4 in chronic hepatitis
      B (CHB). The TLR2 and TLR4 expression on hepatocytes and Kupffer cells from fresh
      liver biopsies was measured from 21 patients with untreated hepatitis B e antigen
      (HBeAg)-positive and HBeAg-negative CHB. Parallel studies were also undertaken on
      monocytes from their peripheral blood. Expression of TLR2 on hepatocytes, Kupffer
      cells, and peripheral monocytes was significantly reduced in patients with HBeAg
      positive CHB in comparison with HBeAg-negative CHB and controls, whereas it was
      significantly increased in HBeAg-negative CHB compared with controls. The level
      of TLR4 expression did not differ significantly between the groups. These results
      were confirmed in vitro using hepatic cell lines transduced with recombinant HBV
      baculovirus expressing wild-type HBV (HBeAg-positive), precore stop codon
      (G1896A) mutant HBV (HBeAg-negative). The functional relevance of these findings
      was established by the demonstration of significantly reduced cytokine production
      (TNF-alpha) and phospho-p38 kinase expression in the presence of the HBeAg. In
      the absence of HBeAg, HBV replication was associated with up-regulation of the
      TLR2 pathway leading to increased TNF-alpha production. CONCLUSION: This study
      demonstrates a potentially important interaction between HBeAg, HBV, and the
      innate immune response.

PMID- 17187405
TI  - Long-acting octreotide versus placebo for treatment of advanced HCC: a randomized
      controlled double-blind study.
AB  - Although numerous treatment modalities have been explored in patients with
      advanced HCC, the therapeutic options are still limited. Somatostatin has been
      shown to have antimitotic activity in endocrine as well as in a variety of
      nonendocrine tumors. Expression of somatostatin receptors is found in HCCs, but
      the efficacy of the somatostatin analogue octreotide remains controversial.
      Therefore, a randomized double-blind placebo-controlled multicenter trial was
      performed to assess the efficacy of long-acting octreotide for the treatment of
      advanced HCC. One hundred twenty untreated patients with histologically confirmed
      HCC were randomized to receive either long-acting octreotide (Sandostation LAR 30
      mg) intramuscularly every 4 weeks or placebo. The study groups were comparable
      with respect to clinical characteristics. There was no difference in the
      cumulative survival. The median survival time was 4.7 months in the octreotide
      group compared with 5.3 months in the control group. Six-month survival rates
      were 41% for octreotide patients and 42% for control patients, respectively. The
      unadjusted relative risk for mortality in the octreotide group compared with
      patients in the control group was 1.11 (95% CI 0.76-1.63; P = 0.59). When
      adjusted for Okuda, CTP, and Cancer of the Liver Italian Program (CLIP) scores,
      the relative risk for octreotide did not change markedly and was 1.05 (95% CI
      0.71-1.55; P = 0.83). The CLIP score seems to predict survival better than both
      Okuda and CTP score. CONCLUSION: The randomized controlled double-blind HECTOR
      trial showed no survival benefit for HCC patients treated with long-acting
      octreotide compared with placebo.

PMID- 17187408
TI  - Bile acids are "homeotrophic" sensors of the functional hepatic capacity and
      regulate adaptive growth during liver regeneration.
AB  - Liver mass depends on one or more unidentified humoral signals that drive
      regeneration when liver functional capacity is diminished. Bile acids are
      important liver products, and their levels are tightly regulated. Here, we
      identify a role for nuclear receptor-dependent bile acid signaling in normal
      liver regeneration. Elevated bile acid levels accelerate regeneration, and
      decreased levels inhibit liver regrowth, as does the absence of the primary
      nuclear bile acid receptor FXR. We propose that FXR activation by increased bile
      acid flux is a signal of decreased functional capacity of the liver. FXR, and
      possibly other nuclear receptors, may promote homeostasis not only by regulating
      expression of appropriate metabolic target genes but also by driving homeotrophic
      liver growth.

PMID- 17187406
TI  - Race, insulin resistance and hepatic steatosis in chronic hepatitis C.
AB  - Hepatic steatosis is common in chronic hepatitis C and has been linked to
      concurrent obesity, insulin resistance, diabetes, disease severity, and poor
      response to therapy. Racial differences in rates of obesity and diabetes may
      contribute to racial differences in hepatic steatosis and treatment response. The
      aim of the present study was to compare hepatic steatosis and its associations
      between African American (AA) and Caucasian American (CA) patients with chronic
      hepatitis C, genotype 1, participating in a prospective study of peginterferon
      and ribavirin therapy. Liver biopsy results were available from 194 AA patients
      and 205 CA patients. The 2 groups were compared for anthropometric, clinical, and
      biochemical features and insulin resistance estimated by the homeostasis model
      assessment index (HOMA-IR). Sixty-one percent of the AA patients and 65% of the
      CA patients had hepatic steatosis (P = 0.38). In univariable analysis, steatosis
      was associated with HOMA-IR, body mass index, waist circumference, serum
      triglycerides, aminotransferase level, and histological scores for inflammation
      and fibrosis. After adjusting for these features, AA patients had a lower risk of
      steatosis than did CA patients (OR 0.54, 95% CI 0.32-0.91, P = 0.02). Insulin
      resistance but not steatosis was associated with a lower rate of sustained
      virological response when adjusted for known factors that predict response
      (relative risk 0.87, 95% CI 0.77-0.99, P = 0.028). CONCLUSION: After adjusting
      for the higher prevalence of features associated with hepatic steatosis, AA
      patients had a lower prevalence of hepatic steatosis than did CA patients with
      chronic hepatitis C, genotype 1. Insulin resistance but not steatosis was
      independently associated with lower sustained virological response.

PMID- 17187407
TI  - Immune role of hepatic TLR-4 revealed by orthotopic mouse liver transplantation.
AB  - Activated CD8+ T cells migrate to the liver at the end of an immune response and
      go through apoptosis there, but this mechanism is impaired in mice lacking Toll
      like receptor-4. This allowed us to test the importance of liver trapping in an
      ongoing immune response. In the absence of Toll-like receptor-4, reduced liver
      accumulation was associated with an increase in the circulating CD8+ T cell pool,
      more long-lived memory T cells and increased CD8+ T cell memory responses. Using
      experimental orthotopic liver transplantation, we showed that the effect of Toll
      like receptor-4 on the formation of the CD8+ T cell memory resides in the liver.
      CONCLUSION: These studies reveal a new function for the liver, which is to
      regulate the magnitude of T cell memory responses through a Toll-like receptor-4
      dependent mechanism.

PMID- 17187409
TI  - Renal failure and bacterial infections in patients with cirrhosis: epidemiology
      and clinical features.
AB  - The aim of the study was to investigate the prevalence and clinical course of
      renal failure that was induced by the various types of bacterial infections in
      patients with cirrhosis and ascites. Three hundred and nine patients, who were
      consecutively admitted to the 3 major hospitals of Padova, Italy, during the
      first 6 months of 2005, were studied prospectively. Of these, 233 patients
      (75.4%) had evidence of ascites. In 104 patients with cirrhosis and ascites
      (44.6%) a bacterial infection was diagnosed. A bacterial infection-induced renal
      failure was observed in 35 of 104 patients (33.6%). The prevalence of renal
      failure was higher in biliary or gastrointestinal tract infections and in
      spontaneous bacterial peritonitis (SBP) and in than in other types of infections.
      In addition, the progressive form of renal failure was only precipitated by
      biliary or gastrointestinal tract infections, SBP, and urinary tract infections
      (UTI). In a multivariate analysis only MELD score (P = 0.001), the peak count of
      neutrophil leukocyte in blood (P = 0.04), and the lack of resolution of infection
      (P = 0.03) had an independent predictive value on the occurrence of renal
      failure. CONCLUSION: The results of the study show that the development of
      bacterial-induced renal failure in patients with cirrhosis and ascites is related
      to the MELD score, and to both the severity and the lack of resolution of the
      infection. A progressive form of renal failure occurs only as a consequence of
      biliary or gastrointestinal tract infections, SBP, and UTI.

PMID- 17187410
TI  - Statins and HCV: a complex issue.

PMID- 17187411
TI  - Transforming growth factor-beta differentially regulates oval cell and hepatocyte
      proliferation.
AB  - Oval cells are hepatocytic precursors that proliferate in late-stage cirrhosis
      and that give rise to a subset of human hepatocellular carcinomas. Although liver
      regeneration typically occurs through replication of existing hepatocytes, oval
      cells proliferate only when hepatocyte proliferation is inhibited. Transforming
      growth factor-beta (TGF-beta) is a key inhibitory cytokine for hepatocytes, both
      in vitro and in vivo. Because TGF-beta levels are elevated in chronic liver
      injury when oval cells arise, we hypothesized that oval cells may be less
      responsive to the growth inhibitory effects of this cytokine. To examine TGF-beta
      signaling in vivo in oval cells, we analyzed livers of rats fed a choline
      deficient, ethionine-supplemented (CDE) diet for phospho-Smad2. Phospho-Smad2 was
      detected in more than 80% of hepatocytes, but staining was substantially reduced
      in oval cells. Ki67 staining, in contrast, was significantly more common in oval
      cells than hepatocytes. To understand the inverse relationship between TGF-beta
      signaling and proliferation in oval cells and hepatocytes, we examined TGF-beta
      signaling in vitro. TGF-beta caused marked growth inhibition in primary
      hepatocytes and the AML12 hepatocyte cell line. Two oval cell lines, LE/2 and
      LE/6, were less responsive. The greater sensitivity of the hepatocytes to TGF
      beta-induced growth inhibition may result from the absence of Smad6 in these
      cells. CONCLUSION: Our results indicate that oval cells, both in vivo and in
      vitro, are less sensitive to TGF-beta-induced growth inhibition than hepatocytes.
      These findings further suggest an underlying mechanism for the proliferation of
      oval cells in an environment inhibitory to hepatocytic proliferation.

PMID- 17187413
TI  - Novel hepatic progenitor cell surface markers in the adult rat liver.
AB  - Hepatic progenitor/oval cells appear in injured livers when hepatocyte
      proliferation is impaired. These cells can differentiate into hepatocytes and
      cholangiocytes and could be useful for cell and gene therapy applications. In
      this work, we studied progenitor/oval cell surface markers in the liver of rats
      subjected to 2-acetylaminofluorene treatment followed by partial hepatectomy (2
      AAF/PH) by using rat genome 230 2.0 Array chips and subsequent RT-PCR,
      immunofluorescent (IF), immunohistochemical (IHC) and in situ hybridization (ISH)
      analyses. We also studied expression of the identified novel cell surface markers
      in fetal rat liver progenitor cells and FAO-1 hepatoma cells. Novel cell surface
      markers in adult progenitor cells included tight junction proteins, integrins,
      cadherins, cell adhesion molecules, receptors, membrane channels and other
      transmembrane proteins. From the panel of 21 cell surface markers, 9 were
      overexpressed in fetal progenitor cells, 6 in FAO-1 cells and 6 are unique for
      the adult progenitors (CD133, claudin-7, cadherin 22, mucin-1, ros-1, Gabrp). The
      specificity of progenitor/oval cell surface markers was confirmed by ISH and
      double IF analyses. Moreover, study of progenitor cells purified with Ep-CAM
      antibodies from D-galactosamine injured rat liver, a noncarcinogenic model of
      progenitor cell activation, verified that progenitor cells expressed these
      markers. CONCLUSION: We identified novel cell surface markers specific for
      hepatic progenitor/oval cells, which offers powerful tool for their
      identification, isolation and studies of their physiology and pathophysiology.
      Our studies also reveal the mesenchymal/epithelial phenotype of these cells and
      the existence of species diversity in the hepatic progenitor cell identity.

PMID- 17187412
TI  - Keratin 18 overexpression but not phosphorylation or filament organization blocks
      mouse Mallory body formation.
AB  - Several human liver diseases are associated with formation of Mallory body (MB)
      inclusions. These hepatocyte cytoplasmic deposits are composed primarily of
      hyperphosphorylated keratins 8 and 18 (K8/K18). Feeding a 3,5-diethoxycarbonyl
      1,4-dihydrocollidine (DDC)-containing diet is a well-established mouse model of
      MBs. K8 overexpression, and K8-null or K18-null mouse models, indicate that a K8
      greater-than-K18 expression ratio is critical for MB formation. We used
      established transgenic mouse models to study the effect of K18 overexpression and
      phosphorylation, or keratin filament disorganization, on MB formation. Five mouse
      lines were used: nontransgenic, those that overexpress wild-type K18 or the K18
      phosphorylation mutants Ser33-to-Ala (S33A) or Ser52-to-Ala (S52A), and mice that
      overexpress K18 Arg89-to-Cys, which causes collapse of the keratin filament
      network into dots. DDC feeding induced MBs in nontransgenic livers, but MBs were
      rarely seen in any of the K18 transgenic mice. Wild-type K18 overexpression
      protected mice from DDC-induced liver injury. CONCLUSION: K18 overexpression
      protects mice from MB formation and from DDC-induced liver injury, which supports
      the importance of the K8-to-K18 ratio in MB formation. The effect of K18 on MB
      formation is independent of hepatocyte keratin filament organization or K18
      Ser33/Ser52 phosphorylation. Keratin filament collapse, which is a major risk for
      acute liver injury, is well tolerated in the context of chronic DDC-mediated
      liver injury.

PMID- 17187414
TI  - Predicting treatment outcome following 24 weeks peginterferon alpha-2a/ribavirin
      therapy in patients infected with HCV genotype 1: utility of HCV-RNA at day 0,
      day 22, day 29, and week 6.

PMID- 17187415
TI  - Ethanol-induced oxidative stress suppresses generation of peptides for antigen
      presentation by hepatoma cells.
AB  - Processing of peptides for antigen presentation is catalyzed by antigen-trimming
      enzymes, including the proteasome and leucine aminopeptidase. Oxidative stress
      suppresses proteasome function. We hypothesized that in liver cells, processing
      of antigenic peptides is altered by ethanol metabolism. To address this issue,
      soluble extracts of ethanol-metabolizing VL-17A cells treated with 100 mM ethanol
      or left untreated were incubated with C-extended or N-extended 18-27 HBV core
      peptides. Peptide cleavage was measured by recovery after HPLC. Ethanol exposure
      to VL-17A cells increased CYP2E1 and decreased proteasome peptidase activities.
      The latter effect was prevented by treatment of cells with inhibitors, 4
      methylpyrazole and diallyl sulfide. Ethanol treatment of VL-17A cells also
      reduced the activity of leucine aminopeptidase (LAP). Consequently, cleavage of
      both C-extended and N-extended peptides by cytosolic extracts was suppressed by
      pretreatment of cells with ethanol. Treatment of cells with interferon gamma,
      which enhances proteasome activity, did not reverse the effects of ethanol.
      Ethanol exerted similar effects on WIFB cells, indicating that its effects are
      not unique to one cell type. CONCLUSION: Ethanol metabolism suppresses activities
      of antigen-trimming enzymes, thereby decreasing the cleavage of C-extended and N
      extended peptides. This defect may potentially result in decreased MHC class I
      restricted antigen presentation on virally infected liver cells.

PMID- 17187416
TI  - Expanding the applicability of noninvasive fibrosis markers in HIV/HCV co
      infected patients.

PMID- 17187417
TI  - A randomized controlled trial of lamivudine to treat acute hepatitis B.
AB  - The role of antivirals in patients with acute viral hepatitis B (AVH-B) has not
      been evaluated in controlled trials. The aim of this study was to evaluate the
      efficacy of lamivudine in patients with AVH-B. AVH-B patients with serum
      bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of
      lamivudine daily for 3 months (group 1, n = 31) or placebo (group 2, n = 40).
      Patients were considered to have severe AVH-B if they fulfilled 2 of 3 criteria:
      (1) hepatic encephalopathy; (2) serum bilirubin > or = 10.0 mg/dL; and (3)
      international normalized ratio (INR) > or = 1.6. At week 4, HBV DNA levels were
      significantly lower (P = 0.037) in group 1 (median: 3.6721 log copies/mL) than
      group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were
      comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR
      values was similar in the 2 groups. Twenty-two patients (71%) in group 1 and 25
      patients (62.5%) in group 2 had severe AVH-B. Results were similar when patients
      with severe AVH-B were analyzed separately. After 12 and 18 months, 93.5% and
      92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%,
      respectively, of patients in the placebo group lost HBsAg. There were no deaths
      in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients
      (85%) in group 2 developed protective anti-HBs titers (P = 0.096). All HBeAg
      positive patients in both groups lost e antigen and anti-HBe developed in 71% and
      87.5% of patients in groups 1 and 2, respectively (P = 0.132). CONCLUSION: Though
      lamivudine causes a greater decrease in levels of HBV DNA, it does not cause
      significantly greater biochemical and clinical improvement as compared to placebo
      in patients with acute hepatitis B.

PMID- 17187418
TI  - Regulation of the UGT1A1 bilirubin-conjugating pathway: role of a new splicing
      event at the UGT1A locus.
AB  - UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in a wide range of
      biological and pharmacological processes because of its critical role in the
      conjugation of a diverse array of endogenous and exogenous compounds. We now
      describe a new UGT1A1 isoform, referred to as isoform 2 (UGT1A1_i2), encoded by a
      1495-bp complementary DNA isolated from human liver and generated by an
      alternative splicing event involving an additional exon found at the 3' end of
      the UGT1A locus. The N-terminal portion of the 45-kd UGT1A1_i2 protein is
      identical to UGT1A1 (55 kd, UGT1A1_i1); however, UGT1A1_i2 contains a unique 10
      residue sequence instead of the 99-amino acid C-terminal domain of UGT1A1_i1. RT
      PCR and Western blot analyses with a specific antibody against UGT1A1 indicate
      that isoform 2 is differentially expressed in liver, kidney, colon, and small
      intestine at levels that reach or exceed, for some tissues, those of isoform 1.
      Western blots of different cell fractions and immunofluorescence experiments
      indicate that UGT1A1_i1 and UGT1A1_i2 colocalize in microsomes. Functional
      enzymatic data indicate that UGT1A1_i2, which lacks transferase activity when
      stably expressed alone in HEK293 cells, acts as a negative modulator of
      UGT1A1_i1, decreasing its activity by up to 78%. Coimmunoprecipitation of
      UGT1A1_i1 and UGT1A1_i2 suggests that this repression may occur via direct
      protein-protein interactions. CONCLUSION: Our results indicate that this newly
      discovered alternative splicing mechanism at the UGT1A locus amplifies the
      structural diversity of human UGT proteins and describes the identification of an
      additional posttranscriptional regulatory mechanism of the glucuronidation
      pathway.

PMID- 17187419
TI  - Intrahepatic delivery of alpha-galactosylceramide-pulsed dendritic cells
      suppresses liver tumor.
AB  - Alpha-galactosylceramide, a glycosphingolipid, mediates interaction of dendritic
      cells (DCs) and NKT cells, leading to activation of both innate and acquired
      immunity. For cancer treatment, conventional DC-based vaccine has been tried, but
      its clinical efficacy is limited against liver cancer. Intrahepatic injection of
      alpha-Galactosylceramide-pulsed DCs (alphaGCDC) has not yet been tested in the
      liver that contains abundant immune cells such as NK, NKT, and T cells. In the
      present study, we examined the efficacy of alphaGCDC administration in comparison
      with p53 peptide-pulsed DCs using a well-established murine CMS4 tumor model.
      Injection of alphaGCDC into CMS4 liver tumors resulted in complete tumor
      rejection and established long-term survival of the animals, while injection of
      p53(232-240) peptide-pulsed DCs (pepDC) only partially suppressed tumor growth in
      the liver. The levels of IFN-gamma in sera of alphaGCDC-treated mice were
      significantly higher than those of pepDC-treated mice. Hepatic NK cells were
      efficiently activated by alphaGCDC injection and played a critical role in liver
      tumor rejection as evidenced by an in vivo antibody-mediated NK cell depletion
      study. Injection of alphaGCDC into liver tumor led to higher p53(232-240) peptide
      specific CD8+ T cell response than that of pepDC. The mice that had been
      protected from CMS4 liver tumor by alphaGCDC injection became resistant to
      subcutaneous CMS4 rechallenge, but not to Colon26 rechallenge. CONCLUSION: These
      results demonstrate that alphaGCDC injection into the liver can efficiently
      activate NK cells that in turn reject liver tumors to establish potent acquired
      immunity against the original tumor.

PMID- 17187420
TI  - Uridine supplementation antagonizes zalcitabine-induced microvesicular
      steatohepatitis in mice.
AB  - Zalcitabine is an antiretroviral nucleoside analogue that exhibits long-term
      toxicity to hepatocytes by interfering with the replication of mitochondrial DNA
      (mtDNA). Uridine antagonizes this effect in vitro. In the present study we
      investigate the mechanisms of zalcitabine-induced hepatotoxicity in mice and
      explore therapeutic outcomes with oral uridine supplementation. BalbC mice (7
      weeks of age, 9 mice in each group) were fed 0.36 mg/kg/d of zalcitabine
      (corresponding to human dosing adapted for body surface), or 13 mg/kg/d of
      zalcitabine. Both zalcitabine groups were treated with or without Mitocnol (0.34
      g/kg/d), a dietary supplement with high bioavailability of uridine. Liver
      histology and mitochondrial functions were assessed after 15 weeks. One mouse
      exposed to high dose zalcitabine died at 19 weeks of age. Zalcitabine induced a
      dose dependent microvesicular steatohepatitis with abundant mitochondria. The
      organelles were enlarged and contained disrupted cristae. Terminal transferase
      dUTP nick end labeling (TUNEL) assays showed frequent hepatocyte apoptosis. mtDNA
      was depleted in liver tissue, cytochrome c-oxidase but not succinate
      dehydrogenase activities were decreased, superoxide and malondialdehyde were
      elevated. The expression of COX I, an mtDNA-encoded respiratory chain subunit was
      reduced, whereas COX IV, a nucleus-encoded subunit was preserved. Uridine
      supplementation normalized or attenuated all toxic abnormalities in both
      zalcitabine groups, but had no effects when given without zalcitabine. Uridine
      supplementation was without apparent side effects. CONCLUSION: Zalcitabine
      induces mtDNA-depletion in murine liver with consequent respiratory chain
      dysfunction, up-regulated synthesis of reactive oxygen species and microvesicular
      steatohepatitis. Uridine supplementation attenuates this mitochondrial
      hepatotoxicity without apparent intrinsic effects.

PMID- 17187421
TI  - Thyroid hormone preconditioning: protection against ischemia-reperfusion liver
      injury in the rat.
AB  - Recently, we reported that oxidative stress due to 3,3',5-triiodothyronine (T(3))
      induced calorigenesis up-regulates the hepatic expression of mediators promoting
      cell protection. In this study, T(3) administration in rats (single dose of 0.1
      mg/kg intraperitoneally) induced significant depletion of reduced liver
      glutathione (GSH), with higher protein oxidation, O(2) consumption, and Kupffer
      cell function (carbon phagocytosis and carbon-induced O(2) uptake). These changes
      occurred within a period of 36 hours of T(3) treatment in animals showing normal
      liver histology and lack of alteration in serum AST and ALT levels. Partial
      hepatic ischemia-reperfusion (IR) (1 h of ischemia via vascular clamping and 20 h
      reperfusion) led to 11-fold and 42-fold increases in serum AST and ALT levels,
      respectively, and significant changes in liver histology, with a 36% decrease in
      liver GSH content and a 133% increase in that of protein carbonyls. T(3)
      administration in a time window of 48 hours was substantially protective against
      hepatic IR injury, with a net 60% and 90% reduction in liver GSH depletion and
      protein oxidation induced by IR, respectively. Liver IR led to decreased DNA
      binding of nuclear factor-kappaB (NF-kappaB) (54%) and signal transducer and
      activator of transcription 3 (STAT3) (53%) (electromobility shift assay), with
      50% diminution in the protein expression of haptoglobin (Western blot), changes
      that were normalized by T(3) preconditioning. CONCLUSION: T(3) administration
      involving transient oxidative stress in the liver exerts significant protection
      against IR injury, a novel preconditioning maneuver that is associated with NF
      kappaB and STAT3 activation and acute-phase response.

PMID- 17187422
TI  - Wnt'er in liver: expression of Wnt and frizzled genes in mouse.
AB  - The Wnt signaling pathway is essential for a wide array of developmental and
      physiological processes. Wnts are extracellular ligands that bind to frizzled
      (Fz) receptors at the membrane, canonically inducing beta-catenin nuclear
      translocation and activation. Although beta-catenin has been shown to be critical
      in liver biology, the expression of the 19 Wnt and 10 Fz genes in liver remains
      undetermined. We report comprehensive analysis of Wnt and Fz expression in whole
      liver as well as individual cell types: freshly isolated and plated hepatocytes,
      biliary epithelial cells, normal and activated stellate and Kupffer cells, and
      sinusoidal endothelial cells (SECs). Oligonucleotides for the 19 Wnt, 10 frizzled
      receptors genes, and secreted Frizzled-related protein-1 (sFRP or Fzb) were
      synthesized based on the available sequences. A total of 11 Wnts and 8 Fz genes
      and Fzb were expressed in normal liver. Although only 6 Wnt and 5 Fz genes were
      expressed in freshly isolated hepatocytes, 8 Wnt genes, 7 Fz genes, and Fzb were
      expressed in plated hepatocytes. Although 12 Wnt and 7 Fz genes were expressed in
      biliary tree, additional Fz9 and Fzb were only expressed in cultured biliary
      epithelial cells. The same 14 Wnt and 7 Fz genes were expressed in both activated
      and normal stellate and Kupffer cells; only Fzb was expressed in their activated
      state. Also, 11 Wnt, seven Fz, and Fzb genes were expressed in SECs. CONCLUSION:
      These data indicate that most Wnt and frizzled genes are expressed in the liver
      and might be playing important roles in liver pathobiology via canonical and
      noncanonical pathways.

PMID- 17187423
TI  - Biliary symptoms, gallbladder motility, and cholecystectomy.

PMID- 17187424
TI  - Prostaglandin I(2) and E(2) mediate the protective effects of cyclooxygenase-2 in
      a mouse model of immune-mediated liver injury.
AB  - Studies of the molecular and cellular mechanisms of concanavalin A (ConA)-induced
      liver injury have provided important knowledge on the pathogenesis of many liver
      diseases involving hepatic inflammation. However, studies identifying hepato
      protective factors based on the mechanistic understanding of this model are
      lacking. Evidence suggests that certain prostaglandin (PG) products of
      cyclooxygenase (COX)-1 and COX-2 provide important anti-inflammatory and
      cytoprotective functions in some pathophysiological states. In the present study,
      we demonstrate a protective role of COX-2 derived PGs in ConA-induced liver
      injury. COX-2(-/-) mice developed much more severe liver damage upon ConA
      treatment compared with wild-type and COX-1(-/-) mice. Treatment of COX-2(-/-)
      mice with misoprostol (a PGE(1/2) analog) or beraprost (a PGI(2) analog)
      significantly decreased ConA-induced liver injury. Data from both in vivo and in
      vitro experiments demonstrated that misoprostol and beraprost acted directly on
      hepatic leukocytes, including natural killer (NK)T and T cells, and down
      regulated their production of interferon (IFN)-gamma, which are critical in
      mediating ConA-induced tissue damage. Collectively, the results provide strong
      evidence that the protective effects of COX-2 within the liver are mediated
      through the production of PGE(2) and PGI(2), which exert anti-inflammatory
      functions. These findings suggest that COX-2-derived PGs may have great
      therapeutic potentials in treating patients with inflammatory liver diseases.

PMID- 17187426
TI  - Sepsis-induced cholestasis.

PMID- 17187425
TI  - Arsenic stimulates sinusoidal endothelial cell capillarization and vessel
      remodeling in mouse liver.
AB  - Trivalent arsenic [As(III)] is a well-known environmental toxicant that causes a
      wide range of organ-specific diseases and cancers. In the human liver, As(III)
      promotes vascular remodeling, portal fibrosis, and hypertension, but the
      pathogenesis of these As(III)-induced vascular changes is unknown. To investigate
      the hypothesis that As(III) targets the hepatic endothelium to initiate
      pathogenic change, mice were exposed to 0 or 250 parts per billion (ppb) of
      As(III) in their drinking water for 5 weeks. Arsenic(III) exposure did not affect
      the overall health of the animals, the general structure of the liver, or
      hepatocyte morphology. There was no change in the total tissue arsenic levels,
      indicating that arsenic does not accumulate in the liver at this level of
      exposure. However, there was significant vascular remodeling with increased
      sinusoidal endothelial cell (SEC) capillarization, vascularization of the
      peribiliary vascular plexus (PBVP), and constriction of hepatic arterioles in
      As(III)-exposed mice. In addition to ultrastructural demonstration of SEC
      defenestration and capillarization, quantitative immunofluorescence analysis
      revealed increased sinusoidal PECAM-1 and laminin-1 protein expression,
      suggesting gain of adherens junctions and a basement membrane. Conversion of SECs
      to a capillarized, dedifferentiated endothelium was confirmed at the cellular
      level with demonstration of increased caveolin-1 expression and SEC caveolae, as
      well as increased membrane-bound Rac1-GTPase. CONCLUSION: These data demonstrate
      that exposure to As(III) causes functional changes in SEC signaling for
      sinusoidal capillarization that may be initial events in pathogenic changes in
      the liver.

PMID- 17187427
TI  - Enhancing hepatitis C treatment uptake and outcomes for injection drug users.

PMID- 17187428
TI  - Hepatitis B virus promotes hepatocarcinogenesis in transgenic mice.
AB  - HBV is a major risk factor for hepatocellular carcinoma (HCC). However, whether
      HBV can directly cause HCC or only indirectly via the induction of chronic liver
      inflammation has been controversial. By using transgenic mice carrying the entire
      HBV genome as a model, we now demonstrate that HBV by itself is an inefficient
      carcinogen. However, it can efficiently promote hepatocarcinogenesis initiated by
      the carcinogen diethylnitrosamine (DEN). This effect of HBV does not involve
      chronic liver inflammation, is apparently due to enhanced hepatocellular
      apoptosis and compensatory regeneration following DEN treatment, and does not
      require the HBV X protein. CONCLUSION: Our results demonstrate a direct role of
      HBV in a hepatocarcinogenesis pathway that involves the interaction between this
      virus and a dietary carcinogen.

PMID- 17187429
TI  - Effect of iron and ascorbate on uroporphyria in ascorbate-requiring mice as a
      model for porphyria cutanea tarda.
AB  - Excess hepatic iron is known to enhance both porphyria cutanea tarda (PCT) and
      experimental uroporphyria. Since previous studies have suggested a role for
      ascorbate (AA) in suppressing uroporphyria in AA-requiring rats (in the absence
      of excess iron), the present study investigated whether AA could suppress
      uroporphyria produced by excess hepatic iron. Hepatic URO accumulation was
      produced in AA-requiring Gulo(-/-) mice by treatment with 3,3',4,4',5
      pentachlorbiphenyl, an inducer of CYP1A2, and 5-aminolevulinic acid. Mice were
      administered either sufficient AA (1000 ppm) in the drinking water to maintain
      near normal hepatic AA levels or a lower intake (75 ppm) that resulted in 70 %
      lower hepatic AA levels. The higher AA intake suppressed hepatic URO accumulation
      in the absence of administered iron, but not when iron dextran (300-500 mg Fe/kg)
      was administered. This effect of iron was not due to hepatic AA depletion since
      hepatic AA content was not decreased. The effect of iron to prevent AA
      suppression of hepatic URO accumulation was not observed until a high hepatic
      iron threshold was exceeded. At both low and high AA intakes, hepatic
      malondialdehyde (MDA), an indicator of oxidative stress, was increased three-fold
      by high doses of iron dextran. MDA was considerably increased even at low iron
      dextran doses, but without any increase in URO accumulation. The level of hepatic
      CYP1A2 was unaffected by either AA intake. CONCLUSION: In this mouse model of
      PCT, AA suppresses hepatic URO accumulation at low, but not high hepatic iron
      levels. These results may have implications for the management of PCT.

PMID- 17187430
TI  - Toll-like receptor-3 and the regulation of intrahepatic immunity: implications
      for interferon-alpha therapy.
AB  - The liver is known to be a classical immunoprivileged site with a relatively high
      resistance against immune responses. Here we demonstrate that highly activated
      liver-specific effector CD8+ T cells alone were not sufficient to trigger immune
      destruction of the liver in mice. Only additional innate immune signals
      orchestrated by TLR3 provoked liver damage. While TLR3 activation did not
      directly alter liver-specific CD8+ T cell function, it induced IFN-alpha and TNF
      alpha release. These cytokines generated expression of the chemokine CXCL9 in the
      liver, thereby enhancing CD8+ T cell infiltration and liver disease in mice.
      Thus, nonspecific activation of innate immunity can drastically enhance
      susceptibility to immune destruction of a solid organ.

PMID- 17187432
TI  - Transcriptome classification of HCC is related to gene alterations and to new
      therapeutic targets.
AB  - Hepatocellular carcinomas (HCCs) are a heterogeneous group of tumors that differ
      in risk factors and genetic alterations. We further investigated transcriptome
      genotype-phenotype correlations in HCC. Global transcriptome analyses were
      performed on 57 HCCs and 3 hepatocellular adenomas and validated by quantitative
      RT-PCR using 63 additional HCCs. We determined loss of heterozygosity, gene
      mutations, promoter methylation of CDH1 and CDKN2A, and HBV DNA copy number for
      each tumor. Unsupervised transcriptome analysis identified 6 robust subgroups of
      HCC (G1-G6) associated with clinical and genetic characteristics. G1 tumors were
      associated with low copy number of HBV and overexpression of genes expressed in
      fetal liver and controlled by parental imprinting. G2 included HCCs infected with
      a high copy number of HBV and mutations in PIK3CA and TP53. In these first
      groups, we detected specific activation of the AKT pathway. G3 tumors were
      typified by mutation of TP53 and overexpression of genes controlling the cell
      cycle. G4 was a heterogeneous subgroup of tumors including TCF1-mutated
      hepatocellular adenomas and carcinomas. G5 and G6 were strongly related to beta
      catenin mutations that lead to Wnt pathway activation; in particular, G6 tumors
      were characterized by satellite nodules, higher activation of the Wnt pathway,
      and E-cadherin underexpression. CONCLUSION: These results have furthered our
      understanding of the genetic diversity of human HCC and have provided specific
      identifiers for classifying tumors. In addition, our classification has potential
      therapeutic implications because 50% of the tumors were related to WNT or AKT
      pathway activation, which potentially could be targeted by specific inhibiting
      therapies.

PMID- 17187434
TI  - Invasive assessment of mitral regurgitation: comparison of hemodynamic
      parameters.
AB  - OBJECTIVES: We sought to analyze several new hemodynamic characteristics which
      address the interplay of left atrial (LA) and left ventricular (LV) pressures, as
      well as to re-analyze several other V wave characteristics employed in the
      determination of mitral regurgitation (MR) severity in order to determine which,
      if any, had adequate correlation with grade of MR for clinical utility.
      BACKGROUND: Invasive assessment of mitral regurgitation includes analysis of
      intracardiac pressures and LV angiography. The V wave, when obtained from the
      pulmonary capillary wedge position (PCWP), and its various characteristics are
      believed to be of limited value for prediction of MR severity. METHOD: We
      analyzed the transeptal pressure tracings of patients with various degrees of MR.
      Several relationships from the simultaneous pressure-time curves of the LA and LV
      were defined. Biplane left ventricular angiography was used to grade MR.
      Correlation between each parameter and MR grade was determined by calculating a
      Pearson correlation coefficient. RESULTS: The ratio of the area under the V wave
      to the LV systolic area (V(a)/LV(a)) best correlates with the degree of MR with a
      Pearson correlation coefficient of 0.60. The V(a)/LV(a) was significantly lower
      in patients with 0-1+ MR compared to > or =2+ MR (0.14 vs. 0.23 p = 0.002).
      CONCLUSIONS: Invasive hemodynamic assessment of MR severity could be enhanced by
      calculating our new ratio, V(a)/LV(a), due to its ability to account for LV work
      that is lost to the LA with a proportional decrease in forward or useful LV work
      with progressively increasing severity of MR.

PMID- 17187433
TI  - Increasing dimethylarginine levels are associated with adverse clinical outcome
      in severe alcoholic hepatitis.
AB  - Previous studies suggest reduced hepatic endothelial nitric oxide synthase
      activity contributes to increased intrahepatic resistance. Asymmetric
      dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, undergoes
      hepatic metabolism via dimethylarginine-dimethylamino-hydrolase, and is derived
      by the action of protein-arginine-methyltransferases. Our study assessed whether
      ADMA, and its stereo-isomer symmetric dimethylarginine (SDMA), are increased in
      alcoholic hepatitis patients, and determined any relationship with severity of
      portal hypertension (hepatic venous pressure gradient measurement) and outcome.
      Fifty-two patients with decompensated alcoholic cirrhosis were studied, 27 with
      acute alcoholic hepatitis and cirrhosis, in whom hepatic venous pressure gradient
      was higher (P = 0.001) than cirrhosis alone, and correlated with ADMA
      measurement. Plasma ADMA and SDMA were significantly higher in alcoholic
      hepatitis patients and in nonsurvivors. Dimethylarginine-dimethylamino-hydrolase
      protein expression was reduced and protein-arginine-methyltransferase-1 increased
      in alcoholic hepatitis livers. ADMA, SDMA and their combined sum, which we termed
      a dimethylarginine score, were better predictors of outcome compared with Pugh
      score, MELD and Maddrey's discriminant-function. CONCLUSION: Alcoholic hepatitis
      patients have higher portal pressures associated with increased ADMA, which may
      result from both decreased breakdown (decreased hepatic dimethylarginine
      dimethylamino-hydrolase) and/or increased production. Elevated dimethylarginines
      may serve as important biological markers of deleterious outcome in alcoholic
      hepatitis.

PMID- 17187435
TI  - Hepatitis C virus eradication in intravenous drug users maintained with
      subcutaneous naltrexone implants.
AB  - The effectiveness of HCV antiviral therapy in patients who have undergone recent
      drug dependency treatment and continue to inject drugs sporadically is presently
      not clear. Patients attending a community-based drug rehabilitation and
      naltrexone implant clinic from October 2002 until March 2005 were screened for
      HCV infection and if positive offered further assessment and treatment with
      interferon and ribavirin therapy. The first 50 patients to commence HCV therapy
      and complete at least 6 months follow-up were prospectively studied. ETR response
      (HCV PCR negative) was 34/50 (68%) and SVR 6 months post-treatment was 31/50
      (62%). Viral eradication was maintained in those 22 patients that have had 12
      months or more post-treatment follow-up. Eleven (22%) patients stopped therapy
      early due to side effects or poor compliance. Only two patients with an ETR
      likely reinfected due to unsafe injection practices. One was re-treated and
      achieved an SVR. Of the patients achieving a 6-month SVR, 17 of 31 patients
      reported no further IDU and 13 of 31 patients occasional IDU during treatment and
      this was maintained after HCV treatment cessation. 46% of patients received
      antidepressant and/or antipsychotic medication during treatment. CONCLUSION: This
      study of HCV treatment in a community-based subcutaneous naltrexone implant
      clinic found antiviral therapy resulted in a 62% SVR. This result is comparable
      to that reported in hospital-based clinics in non-IDU patients. The side effect
      profile and compliance was also similar. HCV antiviral therapy should be offered
      to this large and currently under treated group.

PMID- 17187437
TI  - Linkage between a new splicing site mutation in the MDR3 alias ABCB4 gene and
      intrahepatic cholestasis of pregnancy.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is defined as pruritus and elevated
      bile acid serum concentrations in late pregnancy. Splicing mutations have been
      described in the multidrug resistance p-glycoprotein 3 (MDR3, ABCB4) gene in up
      to 20% of ICP women. Pedigrees studied were not large enough for linkage
      analysis. Ninety-seven family members of a woman with proven ICP were asked about
      pruritus in earlier pregnancies, birth complications and symptomatic gallstone
      disease. The familial cholestasis type 1 (FIC1, ATP8B1) gene, bile salt export
      pump (BSEP, ABCB11) and MDR3 gene were analyzed in 55 relatives. We identified a
      dominant mode of inheritance with female restricted expression and a new intronic
      MDR3 mutation c.3486+5G>A resulting in a 54 bp (3465-3518) inframe deletion via
      cryptic splicing site activation. Linkage analysis of the ICP trait versus this
      intragenic MDR3 variant yielded a LOD score of 2.48. A Bayesian analysis
      involving MDR3, BSEP, FIC1 and an unknown locus gave a posterior probability of
      >0.9966 in favor of MDR3 as causative ICP locus. During the episode of ICP the
      median gamma-glutamyl transpeptidase (gamma-GT) activity was 10 U/l (95% CI, 6.9
      to 14.7 U/l) in the index woman. Four stillbirths were reported in seven
      heterozygous women (22 pregnancies) and none in five women (14 pregnancies)
      without MDR3 mutation. Symptomatic gallstone disease was more prevalent in
      heterozygous relatives (7/21) than in relatives without the mutation (1/34), (P =
      0.00341). CONCLUSION: This study demonstrates that splicing mutations in the MDR3
      gene can cause ICP with normal gamma-GT and may be associated with stillbirths
      and gallstone disease.

PMID- 17187436
TI  - Anti-gp210 and anti-centromere antibodies are different risk factors for the
      progression of primary biliary cirrhosis.
AB  - The predictive role of antinuclear antibodies (ANAs) remains elusive in the long
      term outcome of primary biliary cirrhosis (PBC). The progression of PBC was
      evaluated in association with ANAs using stepwise Cox proportional hazard
      regression and an unconditional stepwise logistic regression model based on the
      data of 276 biopsy-proven, definite PBC patients who have been registered to the
      National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ).
      When death of hepatic failure/liver transplantation (LT) was defined as an end
      point, positive anti-gp210 antibodies (Hazard ratio (HR) = 6.742, 95% confidence
      interval (CI): 2.408, 18.877), the late stage (Scheuer's stage 3, 4) (HR = 4.285,
      95% CI:1.682,10.913) and male sex (HR = 3.266, 95% CI: 1.321,8.075) were
      significant risk factors at the time of initial liver biopsy. When clinical
      progression to death of hepatic failure/LT (i.e., hepatic failure type
      progression) or to the development of esophageal varices or hepatocellular
      carcinoma without developing jaundice (Total bilirubin < 1.5 mg/dL) (i.e., portal
      hypertension type progression) was defined as an end-point in the early stage
      (Scheuer's stage 1, 2) PBC patients, positive anti-gp210 antibodies was a
      significant risk factor for hepatic failure type progression [odds ratio (OR) =
      33.777, 95% CI: 5.930, 636.745], whereas positive anti-centromere antibodies was
      a significant risk factor for portal hypertension type progression (OR = 4.202,
      95% CI: 1.307, 14.763). Histologically, positive anti-gp210 antibodies was most
      significantly associated with more severe interface hepatitis and lobular
      inflammation, whereas positive anticentromere antibodies was most significantly
      associated with more severe ductular reaction. CONCLUSION: These results indicate
      2 different progression types in PBC, hepatic failure type and portal
      hypertension type progression, which may be represented by positive-anti-gp210
      and positive-anticentromere antibodies, respectively.

PMID- 17187439
TI  - Hepatic fibrosis 2006: report of the Third AASLD Single Topic Conference.
AB  - The Third American Associated for the Study of Liver Diseases (AASLD)-sponsored
      Single Topic Conference on hepatic fibrosis was held in June 2006. The conference
      was both international, with 6 countries represented, and cross-disciplinary,
      linking the basic molecular and cellular biology of fibrogenic cells to clinical
      trial design for emerging antifibrotic therapies. The specific goals of the
      conference were: (1) to consolidate knowledge about the natural history of
      fibrosis; (2) to clarify potential endpoints and markers; (3) to emphasize new
      antifibrotic targets developed on the basis of advances in basic science; and (4)
      to understand current critical issues pertaining to clinical trial design. Given
      the tremendous growth of the field and the constraints of a 2-day format, the
      selection of speakers was a challenge. A number of topics not included in the
      oral presentations were featured at poster sessions, lending breadth and depth to
      the meeting as a whole. Surprising new themes emerged about molecular, clinical,
      and regulatory aspects of the field, and a consensus emerged that hepatic
      fibrosis has matured into an integrated discipline that promises to significantly
      improve the prognosis of patients with fibrosing liver disease.

PMID- 17187438
TI  - Bone marrow-derived cells express matrix metalloproteinases and contribute to
      regression of liver fibrosis in mice.
AB  - Liver fibrosis is usually progressive, but it can occasionally be reversible if
      the causative agents are adequately removed or if patients are treated
      effectively. However, molecular mechanisms responsible for this reversibility of
      liver fibrosis have been poorly understood. To reveal the contribution of bone
      marrow (BM)-derived cells to the spontaneous regression of liver fibrosis, mice
      were treated with repeated carbon tetrachloride injections after hematopoietic
      reconstitution with enhanced green fluorescent protein (EGFP)-expressing BM
      cells. The distribution and characteristics of EGFP-positive (EGFP(+)) cells
      present in fibrotic liver tissue were examined at different time points after
      cessation of carbon tetrachloride intoxication. A large number of EGFP(+) cells
      were observed in liver tissue at peak fibrosis, which decreased during the
      recovery from liver fibrosis. Some of them, as well as EGFP-negative (EGFP(-))
      liver resident cells, expressed matrix metalloproteinase (MMP)-13 and MMP-9.
      Whereas MMP-13 was transiently expressed mainly in the cells clustering in the
      periportal areas, MMP-9 expression and enzymatic activity were detected over the
      resolution process in several different kinds of cells located in the portal
      areas and along the fibrous septa. Therapeutic recruitment of BM cells by
      granulocyte colony-stimulating factor (G-CSF) treatment significantly enhanced
      migration of BM-derived cells into fibrotic liver and accelerated the regression
      of liver fibrosis. Experiments using transgenic mice overexpressing hepatocyte
      growth factor (HGF) indicated that G-CSF and HGF synergistically increased MMP-9
      expression along the fibrous septa. CONCLUSION: Autologous BM cells contribute to
      the spontaneous regression of liver fibrosis, and their therapeutic derivation
      could be a new treatment strategy for intractable liver fibrosis.

PMID- 17187440
TI  - Simultaneous positioning of cells into two-dimensional arrays using ultrasound.
AB  - Contactless simultaneous positioning of micrometer-sized particles in suspension
      (e.g., copolymer beads, living cells, silicon microparts) can be performed using
      ultrasound. Current devices are capable of collecting particles into planes or
      lines by exciting a resonance in the fluid by means of a piezoelectric transducer
      located beneath the fluidic cavity and are designed such that a one-dimensional
      pressure field is created. The focus of this work is to collect cells in distinct
      point locations for potential drug screening array applications. A device to
      create two-dimensional arrays of cells within a micromachined chamber is
      described. The chamber is etched into a silicon wafer and sealed with glass; on
      the underside of the silicon layer a piezoelectric actuator is attached. A signal
      is applied to each of two orthogonally aligned strips electrodes defined on the
      surface of the piezoelectric plate. These two strip electrodes create
      independently addressable approximately one-dimensional pressure fields. It is
      shown that by applying the same signal to each electrode a diagonally aligned
      grid of cells can be produced. However, the independence of the two electrodes
      allows the application of two signals with slightly different frequencies to be
      applied which creates a grid of circular cell clumps highly suitable for the
      identified application. (c)

PMID- 17187441
TI  - Cooperativity and saturation in biochemical networks: a saturable formalism using
      Taylor series approximations.
AB  - Cooperative and saturable systems are common in molecular biology. Nevertheless,
      common canonical formalisms for kinetic modeling that are theoretically well
      justified do not have a saturable form. Modeling and fitting data from saturable
      systems are widely done using Hill-like equations. In practice, there is no
      theoretical justification for the generalized use of these equations, other than
      their ability to fit experimental data. Thus it is important to find a canonical
      formalism that is (a) theoretically well supported, (b) has a saturable
      functional form, and (c) can be justifiably applicable to any biochemical
      network. Here we derive such a formalism using Taylor approximations in a special
      transformation space defined by power-inverses and logarithms of power-inverses.
      This formalism is generalized for processes with n-variables, leading to a useful
      mathematical representation for molecular biology: the Saturable and Cooperative
      Formalism (SC formalism). This formalism provides an appropriate representation
      that can be used for modeling processes with cooperativity and saturation. We
      also show that the Hill equation can be seen as a special case within this
      formalism. Parameter estimation for the SC formalism requires information that is
      also necessary to build Power-Law models, Metabolic Control Analysis descriptions
      or (log)linear and Lin-log models. In addition, the saturation fraction of the
      relevant processes at the operating point needs to be considered. The practical
      use of the SC formalism for modeling is illustrated with a few examples. Similar
      models are built using different formalisms and compared to emphasize advantages
      and limitations of the different approaches.

PMID- 17187442
TI  - Dynamic modeling of an enzymatic membrane reactor for the treatment of xenobiotic
      compounds.
AB  - A membrane enzymatic reactor, consisting of a stirred tank coupled to an
      ultrafiltration membrane was set up for the enzymatic oxidation of xenobiotic
      compounds. The azo dye Orange II was selected for the model compound and
      manganese peroxidase for the oxidative enzyme. The ligninolytic cycle was
      initiated and maintained by the controlled addition of all factors (reactants,
      mediators, and stabilizers) at suitable rates. Considering the distinctiveness of
      this process, in which the substrate to be oxidized is not the primary substrate
      for the enzyme, a kinetic model was developed. The azo dye concentration and
      hydrogen peroxide addition rate were found to be the main factors affecting the
      process. The reaction kinetics was defined using a Michaelis-Menten model with
      respect to the Orange II concentration and a first-order linear dependence
      relative to the H(2)O(2) addition rate. The dynamic model, which takes into
      account both the kinetics and the hydraulics of the system, was validated by
      comparing the experimental results in continuous operation under steady and non
      steady state to model predictions. In particular, the model predicted the
      behavior of the system when unexpected alterations in steady-state operation
      occurred. Furthermore, the model allowed us to obtain the most appropriate
      H(2)O(2)/Orange II ratio in the feed to maximize the process efficiency.

PMID- 17187443
TI  - Mineral and iron oxidation at low temperatures by pure and mixed cultures of
      acidophilic microorganisms.
AB  - An enrichment culture from a boreal sulfide mine environment containing a low
      grade polymetallic ore was tested in column bioreactors for simulation of low
      temperature heap leaching. PCR-denaturing gradient gel electrophoresis and 16S
      rRNA gene sequencing revealed the enrichment culture contained an
      Acidithiobacillus ferrooxidans strain with high 16S rRNA gene similarity to the
      psychrotolerant strain SS3 and a mesophilic Leptospirillum ferrooxidans strain.
      As the mixed culture contained a strain that was within a clade with SS3, we used
      the SS3 pure culture to compare leaching rates with the At. ferrooxidans type
      strain in stirred tank reactors for mineral sulfide dissolution at various
      temperatures. The psychrotolerant strain SS3 catalyzed pyrite,
      pyrite/arsenopyrite, and chalcopyrite concentrate leaching. The rates were lower
      at 5 degrees C than at 30 degrees C, despite that all the available iron was in
      the oxidized form in the presence of At. ferrooxidans SS3. This suggests that
      although efficient At. ferrooxidans SS3 mediated biological oxidation of ferrous
      iron occurred, chemical oxidation of the sulfide minerals by ferric iron was rate
      limiting. In the column reactors, the leaching rates were much less affected by
      low temperatures than in the stirred tank reactors. A factor for the relatively
      high rates of mineral oxidation at 7 degrees C is that ferric iron remained in
      the soluble phase whereas, at 21 degrees C the ferric iron precipitated.
      Temperature gradient analysis of ferrous iron oxidation by this enrichment
      culture demonstrated two temperature optima for ferrous iron oxidation and that
      the mixed culture was capable of ferrous iron oxidation at 5 degrees C.

PMID- 17187444
TI  - Kinetics of iron oxidation by Leptospirillum ferriphilum dominated culture at pH
      below one.
AB  - The kinetics of ferrous iron oxidation by Leptospirillum ferriphilum (L.
      ferriphilum) dominated culture was studied in the concentration range of 0.1-20 g
      Fe(2+)/L and the effect of ferric iron (0-60 g Fe(3+)/L) on Fe(2+) oxidation was
      investigated at pH below one. Denaturing gradient gel electrophoresis of PCR
      amplified 16S rRNA genes followed by partial sequencing confirmed that the
      bacterial community was dominated by L. ferriphilum. In batch assays, Fe(2+)
      oxidation started without lag phase and the oxidation was completed within 1 to
      60 h depending on the initial Fe(2+) concentration. The specific Fe(2+) oxidation
      rates increased up to around 4 g/L and started to decrease at above 4 g/L. This
      implies substrate inhibition of Fe(2+) oxidation at higher concentrations.
      Haldane equation fitted the experimental data reasonably well (R(2) = 0.90). The
      maximum specific oxidation rate (q(m)) was 2.4 mg/mg VS . h, and the values of
      the half saturation (K(s)) and self inhibition constants (K(i)) were 413 and
      8,650 mg/L, respectively. Fe(2+) oxidation was competitively inhibited by Fe(3+)
      and the competitive inhibition constant (K(ii)) was 830 mg/L. The time required
      to reach threshold Fe(2+) concentration was around 1 day and 2.3 days with
      initial Fe(3+) concentration of 5 and 60 g/L, respectively. The threshold Fe(2+)
      concentration, below which no further Fe(2+) oxidation occurred, linearly
      increased with increasing initial Fe(2+) and Fe(3+) concentrations. Fe(2+)
      oxidation proceeds by L. ferriphilum dominated culture at pH below 1 even in the
      presence of 60 g Fe(3+)/L. This indicates potential of using and biologically
      regenerating concentrated Fe(3+) sulfate solutions required, for example, in
      indirect tank leaching of ore concentrates.

PMID- 17187445
TI  - Absorption detection of enzymatic reaction using optical microfluidics based
      intermittent flow microreactor system.
AB  - The advantages of integrating microfluidics into photonics-based biosensing for
      fabricating microreactor type lab-on-a-chip devices carries a lot of advantages,
      such as smaller sample volume handling, controlled drug delivery and high
      throughput diagnosis, which is useful for in situ medical diagnosis and point-of
      care (POC) testing. A hybrid integrated optical microfluidic system has been
      developed for the study of single molecules and enzymatic reactions. The method
      of optical absorption has been employed for biosensing and the feasibility of
      absorption-based detection on the microfluidic platform has been demonstrated
      using horseradish peroxidase and hydrogen peroxide, as an example. The results
      show that the device is useful for the analysis of both the individual chemical
      specimen and also the study of chemical and biological reaction between two
      reacting species. The hybrid integration of microfluidics and optical ensembles
      thus forms the basis for developing the microreactor type lab-on-a-chip device,
      which would have several important applications in the area of nanobiotechnology.

PMID- 17187446
TI  - Dynamics of rotating paramagnetic particles simulated by lattice Boltzmann and
      particle dynamics methods.
AB  - Novel biochemical sensors consisting of rotating chains of microscale
      paramagnetic particles have been proposed that would enable convenient, sensitive
      analyte detection. Predicting the dynamics of these particles is required to
      optimise their design. The results of lattice Boltzmann (LB) and particle
      dynamics (PD) simulations are reported, where the LB approach provides a verified
      solution of the complete Navier-Stokes equations, including the hydrodynamic
      interactions among the particles. On the other hand, the simpler PD approach
      neglects hydrodynamic interactions, and does not compute the fluid motion. It is
      shown that macroscopic properties, like the number of aggregated particles,
      depend only on the drag force and not on the total hydrodynamic force, making PD
      simulations yield reasonably accurate predictions. Relatively good agreement
      between the LB and PD simulations, and qualitative agreement with experimental
      data, are found for the number of aggregated particles as a function of the Mason
      number. The drag force on a rotating cylinder is significantly different from
      that on particle chains calculated from both simulations, demonstrating the
      different dynamics between the two cases. For microscopic quantities like the
      detailed force distributions on each particle, the complete Navier-Stokes
      solution, here represented by the LB simulation, is required.

PMID- 17187447
TI  - Developing research capacity building for Aboriginal & Torres Strait Islander
      health workers in health service settings.
AB  - INTRODUCTION: Aboriginal and Torres Strait Islander health workers (hereafter
      called health workers) can play a major role in facilitating culturally
      appropriate health care delivery and program development through the acquisition
      of improved skills in the planning, monitoring and evaluation of these programs
      (RCB). However, many Aboriginal and Torres Strait Islander people and communities
      remain concerned about research and related activities. Health workers are well
      placed to assist communities to not only embrace research, but to be active
      players and promoters of relevant, appropriate and acceptable research. One means
      of achieving the twin goals of RCB and community acceptance and involvement in
      research, is through health workers undertaking research of health priority
      issues and evaluation of activities, such as program delivery, that are of direct
      relevance to their community's aim of improving or enhancing service delivery.
      This article outlines the development and content of a community-based RCB
      framework for health workers. The focus is on the major issues that enhance a
      proactive service delivery model using culturally appropriate research methods.
      Development process: The RCB framework described here was developed, over a
      period of time, through community workshops and consultations aimed at deriving
      general consensus on the key issues and components of a culturally-appropriate,
      community-based training process. The framework has subsequently been reviewed by
      Aboriginal and Torres Strait Islander community representatives from across
      Australia. The overall aim of the framework is to supplement current
      (institutionally-based) education and training resources for health workers with
      community-based research training modules. These modules can be tailored to
      provide research and evaluation skills relevant to health workers taking a more
      proactive role in facilitating health and wellbeing programs in their own
      communities. The use of collaborative consultation and participatory methods are
      intended to be a two-way education process. Course content: A visual pathway is
      used that encompasses the impact of health and practice in the community for
      health workers at a grass-roots level. This enables elements of the RCB process
      to be divided into a series of connected modules. These are: (i 'assessing'
      Existing Services; (ii) methods and measures for Identifying Need at various
      levels; (iii) important issues in Program Development; (iv) how the former
      contributes to Service Improvement; (v) resultant Outcomes that will impact on
      community and service provision; and (vi) Evaluation Methods and applying
      findings to service delivery. CONCLUSIONS: Active participation by the Aboriginal
      and Torres Strait Islander community is fundamental for effective research
      practices and outcomes. The aim is to provide health workers and community
      members with a working knowledge of research ethics and methods so that they can
      assist, monitor and steer the development of culturally appropriate research
      activities that will lead to provision of the highest quality services 'back' to
      the community. This RCB framework will enable health workers to be more
      proactive, self-reliant and self-sufficient within their community and healthcare
      settings.

PMID- 17187448
TI  - Decoy receptor-2 small interfering RNA (siRNA) strategy employing three different
      siRNA constructs in combination defeats adenovirus-transferred tumor necrosis
      factor-related apoptosis-inducing ligand resistance in lung cancer cells.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively
      induces apoptosis in cancer cells but not in normal cells. However, studies have
      indicated that more than half of human tumors exhibit TRAIL resistance. Although
      the mechanism of TRAIL resistance is not understood, it represents a barrier to
      any TRAIL-mediated gene therapy approach. In addition, no correlation between
      TRAIL receptor (TRAIL-R) expression profile and TRAIL resistance has been
      demonstrated in cancer cells. In this study, three different lung cancer cell
      lines and three different primary cell cultures established from patients with
      lung cancer (two patients with squamous cell lung carcinoma and one with
      adenocarcinoma) were screened for sensitivity to adenoviral delivery of TRAIL.
      Whereas TRAIL-resistant primary lung cell cultures and the A549 lung cancer cell
      line exhibited high levels of surface decoy receptor-2 (DcR2/TRAIL-R4)
      expression, TRAIL-sensitive lung cancer cell lines (HBE and H411) failed to
      express it. A DcR2 short interfering RNA (siRNA) approach involving three
      different siRNA constructs in combination downregulated DcR2/TRAIL-R4 expression
      and sensitized lung cancer cells to TRAIL-induced apoptosis. Immunohistochemical
      staining of samples from 10 patients with lung carcinoma suggested that high
      level DcR2/TRAIL-R4 expression is a common phenotype observed in patients with
      non-small cell lung carcinoma.

PMID- 17187451
TI  - Coronary calcium: does it still play a role in the age of CT angiography.

PMID- 17187453
TI  - Dofetilide: a new class III antiarrhythmic agent.
AB  - Dofetilide is a relatively new class III antiarrhythmic agent that selectively
      blocks the rapid component of the cardiac ion channel delayed rectifier current.
      This results in an increase in the action potential duration and effective
      refractory period of the myocyte, thereby terminating reentrant tachyarrhythmias
      and preventing their re-induction. Oral dofetilide is effective in the conversion
      of atrial fibrillation and flutter to sinus rhythm and in the maintenance of
      sinus rhythm after conversion. It is generally well tolerated but like other
      antiarrhythmic agents in its class, torsades de pointes may be induced as a
      consequence of therapy. This risk is minimized by dosage adjustment according to
      creatinine clearance and QT(c) interval, by selecting patients without known risk
      factors for torsades and by initiating treatment in a monitored hospital setting
      for the first 3 days. Unlike other antiarrhythmic agents, oral dofetilide did not
      increase mortality in patients with a recent myocardial infarction or congestive
      heart failure, hence its importance as an alternative medication for the
      pharmacological conversion of atrial fibrillation and flutter, and maintenance of
      sinus rhythm after conversion in patients at high risk of sudden death.

PMID- 17187454
TI  - Carvedilol: use in chronic heart failure.
AB  - Carvedilol is a beta-adrenergic antagonist with vasodilatory properties (alpha1
      antagonism), which has been extensively evaluated in the treatment of patients
      with heart failure. In patients with chronic heart failure carvedilol improves
      left-ventricular (LV) ejection fraction over 6 to 12 months of treatment, and
      attenuates LV remodelling. Large-scale randomised, placebo controlled trials
      involving more than 4000 patients with chronic heart failure have demonstrated
      that carvedilol improves survival and reduces hospitalizations. Comparative
      studies with metoprolol in patients with heart failure have suggested that
      carvedilol may be associated with greater survival benefit although differences
      in the preparation of metoprolol have left uncertainty in this area. Carvedilol
      has a high safety profile and the clinical benefits appear maintained across a
      wide range of patients with comorbidities such as diabetes and renal failure.
      Carvedilol has also been shown to attenuate LV remodeling and improve clinical
      outcomes in patients with LV dysfunction and/or heart failure following acute
      myocardial infarction. As a result of these data, carvedilol is recommended for
      treatment of patients with heart failure in heart-failure guidelines. This
      evidence-based treatment should be widely implemented to ensure that patients
      with heart failure receive appropriate medical therapy.

PMID- 17187455
TI  - Isolation and expansion of resident cardiac progenitor cells.
AB  - After myocardial infarction, loss of viable cardiomyocytes severely impairs
      cardiac function. Recently, stem cell transplantation has been put forward as a
      promising approach to repair the damaged heart. Although several clinical trials
      have already been performed, the dominant beneficial effects are probably due to
      neoangiogenesis and arteriogenesis. However, replacement of cardiomyocytes is
      vital to improve cardiac function in the long term. Stem cells and progenitor
      cells, with the capacity to differentiate into cardiomyocytes, have been
      described in both embryonic and adult tissues. Upon stimulation, cardiac
      progenitor cells proliferate and differentiate into cardiomyocytes, vascular
      smooth muscle cells, and endothelial cells. Currently however, high proliferation
      rates and differentiation of cardiac progenitor cells beyond the fetal stage have
      not yet been achieved. Full differentiation into adult cardiomyocytes in vitro
      and in vivo might be important for efficient integration with the host
      environment and therefore more research is needed to study factors that influence
      proliferation and differentiation. Here we will discuss the isolation of cardiac
      progenitor cells, their potential to differentiate into various cell types needed
      for cardiac repair, the possible mechanisms behind these events, and how these
      cells may be implemented in future clinical settings.

PMID- 17187456
TI  - Platelet P2 receptors: old and new targets for antithrombotic drugs.
AB  - Platelets possess three P2 receptors for adenine nucleotides: P2Y1 and P2Y12,
      which interact with ADP, and P2X1, which interacts with ATP. The interaction of
      adenine nucleotides with their platelet receptors plays an important role in
      thrombogenesis. The thienopyridine ticlopidine, an antagonist of the platelet
      P2Y12 ADP receptor, reduces the incidence of vascular events in patients at risk,
      but it also has some important drawbacks: a relatively high incidence of toxic
      effects; delayed onset of action; high inter-individual variability in response.
      Another thienopyridine, clopidogrel, has superseded ticlopidine, because it is an
      efficacious antithrombotic drug and is less toxic than ticlopidine. However, the
      high inter-patient variability in response still remains an important issue.
      These drawbacks justify the continuing search for agents that can further improve
      the clinical outcome of patients with atherosclerosis through greater efficacy
      and/or safety. A new thienopyridyl compound prasugrel, which is characterized by
      higher potency and faster onset of action compared with clopidogrel, is currently
      under clinical evaluation. Two direct and reversible P2Y12 antagonists, cangrelor
      and AZD6140, have very rapid onset and reversal of platelet inhibition, which
      make them attractive alternatives to thienopyridines, especially when rapid
      inhibition of platelet aggregation or its quick reversal are required. Along with
      new P2Y12 antagonists, inhibitors of the other platelet receptor for ADP, P2Y1,
      and of the receptor for ATP, P2X1, are under development and may prove to be
      effective antithrombotic agents.

PMID- 17187457
TI  - Direct thrombin inhibition during percutaneous coronary intervention in patients
      with heparin-induced thrombocytopenia.
AB  - Patients with or at risk of heparin-induced thrombocytopenia (HIT) who are
      undergoing percutaneous coronary intervention (PCI) are at particular risk of
      thrombosis due to the prothrombotic nature of HIT and the endovascular disruption
      from PCI. Patients require aggressive anticoagulation during PCI, and
      alternative, nonheparin anticoagulation is recommended over heparin in patients
      with acute or previous HIT. Argatroban, bivalirudin, and lepirudin are
      nonheparin, fast-acting, parenteral direct thrombin inhibitors (DTIs).
      Multicenter, prospective studies have demonstrated that argatroban and lepirudin
      each reduce thrombosis in HIT and that argatroban and bivalirudin each provide
      adequate anticoagulation during PCI in patients with or at risk of HIT. We review
      current therapeutic practices with direct thrombin inhibitors in patients with or
      at risk of HIT during PCI, including individuals requiring periprocedural
      anticoagulation, and the factors influencing the choice of DTI in this setting.

PMID- 17187459
TI  - Role of intravascular ultrasound in unprotected left main percutaneous coronary
      intervention.
AB  - Percutaneous coronary intervention (PCI) to the unprotected left main stem offers
      an attractive alternative to bypass grafting, but is associated with a
      significant clinical risk and therefore demands special consideration. Successful
      left main PCI is dependent upon the morphology of the lesion and the technical
      quality of the procedure. For these reasons, intravascular ultrasound (IVUS) has
      been the most popular adjunct to coronary angiography during left main PCI.
      However, trials of IVUS in left main PCI have produced inconclusive results, and
      most data predate the use of drug-eluting stents. Despite this, IVUS offers
      practical benefits in both case selection, and in guiding angioplasty and
      stenting. Here, we review the arguments for the present and future role of IVUS
      in left main PCI.

PMID- 17187460
TI  - Monitoring and imaging the clot during systemic thrombolysis in stroke patients.
AB  - Intravenous thrombolysis is the only approved treatment for acute ischemic stroke
      when administered within the first 3 h of stroke onset. Response to systemic
      thrombolysis depends on several factors including the location of arterial
      occlusion, clot characteristics and, ultimately, the embolic source. In the last
      few years, tremendous progress has been made, resulting in the widespread
      implementation of noninvasive neurovascular techniques. These imaging modalities
      are being increasingly performed in the acute stroke setting, without substantial
      delay, in a large number of centers worldwide. Transcranial Doppler ultrasound
      provides a unique opportunity to assess several aspects of clot dissolution by
      means of continuous monitoring of recanalization during and after tissue
      plasminogen activator administration. This approach allows for the evaluation of
      patients at the bedside and in real time due to the commencement, timing, speed
      and degree of artery reopening in addition to allowing the documentation of
      reocclusion after successful recanalization. Gradient refocused echo
      susceptibility vessel sign (GRE SVS) magnetic resonance imaging may be
      particularly useful for the identification of an intravascular thrombus during
      the acute phase of ischemic stroke; GRE SVS may represent a surrogate of clot
      composition and differential response to thrombolysis. The increasing
      availability of advanced neurovascular techniques may, in the near future,
      improve the design of stroke trials. The capability of these techniques to assess
      not only tissue viability but also key aspects regarding susceptibility to
      thrombolysis such as location, amount, composition, and age of the offending clot
      may improve the safety and efficacy profile of thrombolytic therapy for acute
      ischemic stroke.

PMID- 17187458
TI  - MRI of atherosclerosis: diagnosis and monitoring therapy.
AB  - Atherosclerosis is a prevalent disease affecting millions of Americans. Despite
      our advances in diagnosis and treatment, atherosclerosis is the leading cause of
      death in America. High-resolution magnetic resonance imaging has overcome the
      limitations of current angiographic techniques and has emerged as a leading
      noninvasive imaging modality for atherosclerotic disease. Atherosclerosis of the
      arterial wall of the human carotid, aortic, peripheral and coronary arteries have
      all been successfully evaluated. In addition, the power of magnetic resonance
      imaging to differentiate the major components of atherosclerotic plaque has been
      validated. The ability to image the vessel wall and risk stratify atherosclerotic
      plaque will create management decisions not previously faced, and has the
      potential to change the way atherosclerosis is treated.

PMID- 17187461
TI  - Cardiomyopathy of Duchenne muscular dystrophy: pathogenesis and prospect of
      membrane sealants as a new therapeutic approach.
AB  - Duchenne muscular dystrophy (DMD) is a devastating progressive disease of
      striated muscle deterioration. This fatal X-linked disorder results from the loss
      of the protein dystrophin, which in turn causes striated muscle membrane
      instability. Cardiac dysfunction is a growing problem in patients with DMD, but
      relatively little is known about the pathophysiology of the dystrophic heart. At
      present, there is no effective treatment for DMD and the current clinical
      approaches are primarily supportive in nature. This review will discuss the
      pathogenesis of DMD in the heart and discuss how these pathogenic processes have
      led to a new class of agents directed specifically at restoring membrane
      integrity to dystrophic myocardium. The tri-block poloxamers, specifically
      poloxamer 188 (P188), are able to stabilize the membranes of dystrophic
      myocardium in animal models and may offer a new therapeutic approach for cardiac
      disease in DMD.

PMID- 17187462
TI  - Electrophysiological interventions for treatment of congestive heart failure in
      pediatrics and congenital heart disease.
AB  - Heart failure therapy, while well tested in the adult population, therapeutic
      interventions are less well defined in the pediatric population. Several
      treatment strategies are available for the adult patient with heart failure,
      thought few of these therapies have been proven in children. Morbidity and
      mortality in the pediatric population with a failing heart is significant, and
      rhythm management as well as strategies to improve hemodynamics are important in
      the care of these children. This review will address issues of rhythm management
      and resynchronization therapy in pediatric and congenital heart disease patients
      with heart failure.

PMID- 17187463
TI  - Beta-adrenergic pathways in human heart failure.
AB  - Beta-adrenergic receptor activation plays an important role in the progression of
      human heart failure and the treatment of patients with beta-blockers has greatly
      improved the outcome of the disease. However, heart failure still is one of the
      leading causes of death in various countries and there is an imperative need for
      additional targets for the treatment of the disease. Recent studies by various
      groups have analyzed the downstream signaling pathways activated in response to
      beta-adrenergic stimulation that have the potential to become important targets
      for future treatments of heart failure. This review focuses on the significance
      of these pathways in the pathophysiology of heart failure in response to beta
      adrenergic stimulation. More specifically the roles of PDE3, phosphorylation of
      phospholamban, and CaMKII activation are extensively discussed.

PMID- 17187464
TI  - Cell transplantation for treatment of left-ventricular dysfunction due to
      ischemic heart failure: from bench to bedside.
AB  - Cell transplantation is an innovative technology that involves the implantation
      of a variety of myogenic and angiogenic cell types. The transplanted cells
      proliferate and augment left ventricular performance and therein ameliorate the
      heart failure symptoms. The concept of cell transplantation has followed the
      footsteps of angiogenesis starting as bench side research. The latter half of the
      decade saw the transformation of this potential mechanism to a promising therapy
      for ischemic heart failure. More than 150 patients have been treated with
      cellular transplantation worldwide. This novel application has the potential to
      revolutionize alternative therapeutic approaches to management of heart failure.

PMID- 17187465
TI  - Therapeutic applications of transcranial ultrasound devices.

PMID- 17187466
TI  - Telemedicine: challenges and opportunities.

PMID- 17187467
TI  - XIENCE V everolimus-eluting coronary stent system: a novel second generation drug
      eluting stent.
AB  - Drug-eluting stents (DES) have been shown to be safe and significantly reduce
      clinical events and angiographic restenosis in the percutaneous treatment of
      coronary artery disease. Currently, three DES have been approved in Europe and
      Northern America: the sirolimus-eluting stent (SES), the paclitaxel-eluting stent
      (PES) and the zotarolimus-eluting stent (ZES). Everolimus, an analog of
      sirolimus, is an immunosuppressive and antiproliferative agent. In three studies,
      the SPIRIT I, FUTURE I and II, the everolimus-eluting stent has proven to be
      safe, well-tolerated and has shown very favorable clinical and angiographic
      results. Compared with earlier-generation DES, the XIENCE V everolimus-eluting
      coronary stent system (Advanced Cardiovascular Systems Inc., an Abbott Vascular
      Company, CA, USA) may provide enhanced deliverability, radiopacity with thinner
      strut filaments and, owing to a durable polymer, sustained drug elution and
      vascular compatibility.

PMID- 17187468
TI  - P-Stim auricular electroacupuncture stimulation device for pain relief.
AB  - Acupuncture is now accepted as a complementary analgesic treatment. Auricular
      acupuncture is a distinct form of acupuncture. Electrical stimulation of
      acupoints (electroacupuncture) increases the effects of acupuncture. Recently, an
      auricular electroacupuncture device, the P-Stim, has become available. Clinical
      studies in outpatients have investigated the P-Stim in chronic musculoskeletal
      pain and its use for minor surgery. In chronic cervical or low back pain,
      auricular electroacupuncture was more effective than conventional auricular
      acupuncture. The results in acute pain were controversial. Auricular
      electroacupuncture reduced pain and remifentanil consumption during oocyte
      aspiration when compared with conventional auricular acupuncture or a sham
      treatment. However, after third molar tooth extraction, auricular
      electroacupuncture and auricular acupuncture failed to reduce either
      postoperative pain or analgesic consumption. Further large-scale studies are
      required to evaluate the analgesic efficacy of auricular electroacupuncture.

PMID- 17187469
TI  - Intraoperative neurophysiological monitoring technology: recent advances and
      evolving uses.
AB  - Intraoperative neurophysiological monitoring has evolved over the last 25 years
      to become an important component of many types of orthopedic and neurosurgical
      procedures. From its foundations in VIII cranial nerve surgeries and scoliosis
      corrections surgeries, intraoperative neurophysiological monitoring has expanded
      to incorporate nearly all spine procedures and many involving the brain and
      brainstem. Fundamental to this growth in the use of intraoperative
      neurophysiological monitoring has been the development of the technology used to
      perform the neurophysiological tests. Advancements in electronics and computer
      technology have resulted in significant improvements in the capacity, ease of
      use, quality and reliability of the equipment as well as the quality of and
      control over the acquired data. These technological advancements have resulted in
      remarkable improvements in not only the quality and availability of
      intraoperative neurophysiological monitoring, but also, as a consequence, patient
      care, and have arguably propelled the expansion of the use that intraoperative
      neurophysiological monitoring has seen over the last 10 years.

PMID- 17187470
TI  - Neural machine interfaces for controlling multifunctional powered upper-limb
      prostheses.
AB  - This article investigates various neural machine interfaces for voluntary control
      of externally powered upper-limb prostheses. Epidemiology of upper limb
      amputation, as well as prescription and follow-up studies of externally powered
      upper-limb prostheses are discussed. The use of electromyographic interfaces and
      peripheral nerve interfaces for prosthetic control, as well as brain machine
      interfaces suitable for prosthetic control, are examined in detail along with
      available clinical results. In addition, studies on interfaces using muscle
      acoustic and mechanical properties and the problem of interfacing sensory
      information to the nervous system are discussed.

PMID- 17187471
TI  - Selfprotective smart orthopedic implants.
AB  - In this review, we discuss current advances leading to an exciting change in
      implant design for orthopedic surgery. The initial biomaterial approaches in
      implant design are being replaced by cellular-molecular interactions and
      nanoscale chemistry. New designs address implant complications, particularly
      loosening and infection. For infection, local delivery systems are an important
      first step in the process. Selfprotective 'smart' devices are an example of the
      next generation of orthopedic implants. If proven to be effective, antibiotics or
      other active molecules that are tethered to the implant surface through a
      permanent covalent bond and tethering of antibiotics or other biofactors are
      likely to transform the practice of orthopedic surgery and other medical
      specialties. This new technology has the potential to eliminate periprosthetic
      infection, a major and growing problem in orthopedic practice.

PMID- 17187472
TI  - Gastrointestinal tissue engineering.
AB  - Tissue engineering is an emerging discipline that combines engineering principles
      and the biological sciences toward the development of functional replacement
      tissue. Virtually every tissue in the body has been investigated and tremendous
      advances have been made in many areas. This article focuses on the
      gastrointestinal tract and reviews the current status of bioengineering
      gastrointestinal tissues, including the esophagus, stomach, small intestine and
      colon. Although progress has been achieved, there continues to be significant
      challenges that need to be addressed.

PMID- 17187473
TI  - Cuffed tracheal tubes in children: past, present and future.
AB  - This article reviews recent developments and core topics in the use and design of
      pediatric cuffed tracheal tubes. A concept for an appropriate pediatric cuffed
      tracheal tube is introduced. The main points in this concept are evidence-based
      tracheal tube size recommendation, continuous cuff pressure monitoring and a
      pediatric tracheal tube with an anatomically-based intubation depth mark and a
      short distally placed high-volume-low pressure cuff made from an ultra-thin
      polyurethane membrane with markedly improved tracheal sealing performance. The
      main points in proper handling of cuffed tracheal tubes in children are
      highlighted. Finally, an outlook on future developments in the design of
      pediatric cuffed tracheal tubes and an overview of tasks to be performed in
      evaluating them is given.

PMID- 17187474
TI  - Diffuse optical imaging and spectroscopy for cancer.
AB  - Visible light and near infrared light interact with biological tissue by
      absorption and scattering. Diffuse optical imaging and spectroscopy reconstructs
      tissue physiologic parameters based on noninvasive measurement of tissue optical
      properties. This technology can be used to differentiate physiologic and
      molecular signatures of both malignant and benign tissues, as they relate to the
      area of cancer research. Major advantages are the use of non-ionizing radiation,
      real-time continuous data acquisition, low cost, and portability. Limitations
      include low spatial resolution and limited reproducibility. This paper reviews
      the currently available state-of-the-art technologies for diffuse optical imaging
      and spectroscopy and their applications in cancer research.

PMID- 17187475
TI  - Drug-eluting stents will carry a warning.

PMID- 17187476
TI  - Rapid construction of small interfering RNA-expressing adenoviral vectors on the
      basis of direct cloning of short hairpin RNA-coding DNAs.
AB  - In the conventional method for constructing an adenoviral (Ad) vector expressing
      small interfering RNA (siRNA), short hairpin RNA (shRNA)-coding oligonucleotides
      are introduced downstream of a polymerase III (or polymerase II)-based promoter
      cloned into a shuttle plasmid. An siRNA expression cassette, which is cloned into
      the shuttle plasmid, is then introduced into the E1 deletion region of the Ad
      vector plasmid by in vitro ligation or homologous recombination in Escherichia
      coli, and the linearized plasmid is transfected into 293 cells, generating an Ad
      vector expressing siRNA. Therefore, two-step plasmid manipulation is required. In
      this study, we developed a method by which shRNA-coding oligonucleotides can be
      introduced directly into the Ad vector plasmid. To do this, we constructed a new
      vector plasmid into which the human U6 promoter sequence was cloned in advance.
      Unique restriction enzyme sites were introduced at the transcription start site
      of the U6 promoter sequence in the vector plasmid. Luciferase and p53 genes were
      efficiently knocked down by Ad vectors generated by the new method and expressing
      siRNA against the target gene. This method should be useful for RNA interference
      based experiments, and should make it easy to construct an siRNA-expressing Ad
      vector library for functional screening.

PMID- 17187477
TI  - Drug discovery without a molecular target: the road less traveled.

PMID- 17187479
TI  - Fluorescent proteins in drug development. 13-14 November 2006, La Jolla,
      California, USA.

PMID- 17187480
TI  - Fluorescence in situ hybridization: a multitarget approach in diagnosis and
      management of urothelial cancer.
AB  - Noninvasive tests for detecting genetic or molecular alterations in urine
      indicative of urothelial cancer are increasingly becoming the focus of urological
      cancer research. Since its approval by the US FDA in 2001, the fluorescence in
      situ hybridization test (Vysis UroVysion) has been widely evaluated. In general,
      published data demonstrate better sensitivity and equal or better specificity
      compared with routine cytology, which is still considered the 'gold standard' in
      diagnosing and monitoring bladder tumors. However, the fluorescence in situ
      hybridization test seems to provide not only a useful tool in bladder cancer
      detection, but also in the diagnosis of upper urinary tract tumors, surveillance
      and determining therapy effectiveness. This multitarget assay that detects four
      different chromosomal aberrations in tumor cells is a kind of objective molecular
      cytology and has proven advantages over routinely used cytology.

PMID- 17187481
TI  - Galactomannan antigen detection in the diagnosis of invasive aspergillosis.
AB  - Invasive aspergillosis is a serious and lethal infection among immunocompromised
      patients, with reported mortality rates as high as 74-92%. The high mortality is
      related to the severe immunosuppression experienced by these patients as well as
      the difficulties for physicians in arriving at a timely diagnosis. Definitive
      diagnostic procedures (tissue biopsy for histopathology and culture) are often
      precluded by severe cytopenias and coagulation abnormalities. The development of
      minimally invasive, nonculture diagnostic methods is a major advance in the early
      diagnosis of invasive aspergillosis. Galactomannan is a heteropolysaccharide
      (mannan core and side residues of galactofuranosyl units) present in the cell
      wall of Aspergillus spp. The double sandwich enzyme immunoassay, which detects
      galactomannan in serum samples, has been available in Europe for almost a decade
      and in the USA since May 2003, for the diagnosis of invasive aspergillosis.
      However, availability of the double galactomannan enzyme immunoassay is center
      variable in the USA and, although its analytical performance in the diagnosis of
      invasive aspergillosis is well documented, its routine use in clinical practice
      is limited. As an adjunct in the diagnosis and management of invasive
      aspergillosis, incorporation of the galactomannan enzyme immunoassay into
      clinical trials will help to further define its role.

PMID- 17187482
TI  - Preimplantation genetic diagnosis for monogenic diseases: overview and emerging
      issues.
AB  - Preimplantation genetic diagnosis (PGD) is an established reproductive option for
      couples at risk of conceiving a pregnancy affected with a known genetic disease,
      who wish to avoid an (additional) affected child, termination of pregnancy or
      recurrent miscarriages. Early technologies concentrated on different approaches
      to direct mutation testing for monogenic diseases using single cell PCR
      protocols, or sex selection by fluorescent in situ hybridization for X-linked
      monogenic disease. Development of multiplex fluorescent PCR allowed
      simultaneously testing of linked markers alongside the mutation test, increasing
      the accuracy by controlling for contamination and identifying allele drop-out.
      The advent of highly effective whole genome amplification methods has opened the
      way for new technologies such as preimplantation genetic haplotyping and
      microarrays, thus increasing the number of genetic defects that can be detected
      in preimplantation embryos; the number of cases carried out and the new
      indications tested increases each year. Different countries have taken very
      different approaches to legislating and regulating PGD, giving rise to the
      phenomenon of reproductive tourism. PGD is now being performed for scenarios
      previously not undertaken using prenatal diagnosis, some of which raise
      significant ethical concerns. While PGD has benefited many couples aiming to have
      healthy children, ethical concerns remain over inappropriate use of this
      technology.

PMID- 17187483
TI  - Unraveling the genetics of atherosclerosis: implications for diagnosis and
      treatment.
AB  - The hereditary aspect of atherosclerosis has been known for some time in clinical
      medicine. Over the past three decades, a great deal of research has focused on
      defining the genetic component of this disease with the hopes that detailed
      knowledge of the genes and gene variants will lead to improvements in the
      diagnosis and treatment. This article reviews the different approaches for
      studying the genetics of atherosclerosis and the potential for using the results
      in clinical practice.

PMID- 17187484
TI  - HER2 testing: a review of detection methodologies and their clinical performance.
AB  - The ERBB2 proto-oncogene, commonly referred to as the human epidermal growth
      factor receptor-2 (HER2) gene, encodes a 185 kd receptor tyrosine kinase.
      Overexpression of the protein leads to constitutive activity of the HER2 receptor
      and breast tumor development through enhanced cell proliferation, survival,
      motility and adhesion. Overabundance of the HER2 receptor, typically caused by
      amplification of the HER2 gene, is present in approximately 10-30% of invasive
      breast cancers, and is associated with an aggressive disease course and decreased
      disease-free and overall survival in node-positive patients. Tratuzumab, a
      humanized murine monoclonal antibody, offers a targeted treatment modality for
      tumors that over express the HER2 protein. Tratuzumab, shown to be effective and
      initially approved for treatment of metastatic breast cancer, has recently been
      shown to be very effective in the adjuvant setting. Thus, to offer prognostic
      information and to direct appropriate treatment it is important to provide
      accurate laboratory assessment of the status of HER2. This article provides an
      overview of the methods currently used to assess HER2.

PMID- 17187485
TI  - Arrayed identification of DNA signatures.
AB  - Over the last few years, several initiatives have described efforts to combine
      previously invented techniques in molecular biology with parallel detection
      principles to sequence or genotype DNA signatures. The Infinium system from
      Illumina and the Affymetrix GeneChips are two systems suitable for whole-genome
      scoring of variable positions. However, directed candidate-gene approaches are
      more cost effective and several academic groups and the private sector provide
      techniques with moderate typing throughput combined with large sample capacity
      suiting these needs. Recently, whole-genome sequencing platforms based on the
      sequencing-by-synthesis principle were presented by 454 Life Sciences and Solexa,
      showing great potential as alternatives to conventional genotyping approaches. In
      addition to these sequencing initiatives, many efforts are pursuing novel ideas
      to facilitate fast and cost-effective whole genome sequencing, such as ligation
      based sequencing. Reliable methods for routine re-sequencing of human genomes as
      a tool for personalized medicine, however, remain to be developed.

PMID- 17187486
TI  - Molecular profiling of lung carcinoma: identifying clinically useful tumor
      markers for diagnosis and prognosis.
AB  - The overall survival of patients with lung cancer is dismal despite extensive
      effort in improvement of diagnosis and treatment. A better understanding of the
      multistep genetic and epigenetic alterations in lung cancer pathogenesis and
      progression is necessary for development of improved diagnostic approaches and
      new targeted therapies. Identification of molecular alterations in the early lung
      carcinogenesis, together with advanced molecular techniques, may facilitate
      development of rapid and effective methods for early diagnosis and prognosis of
      lung carcinoma. In this review, we discuss current understanding of lung
      carcinogenesis and prospective molecular markers in lung cancer diagnosis.
      Although the impact of translating new technologies into clinical practice on
      survival has not been completely determined, they offer a new avenue of exciting
      novel approaches to early diagnosis of this deadly disease.

PMID- 17187487
TI  - Multiplexing molecular diagnostics and immunoassays using emerging microarray
      technologies.
AB  - Enzyme-linked immunosorbent assays (ELISA) are frequently used for quantitative
      measurement of the presence of protein, for single-analyte testing, in a sample.
      The application of ELISA in a microarray format has the potential to
      simultaneously measure the presence and/or concentrations of numerous proteins,
      in multiplex testing, all contained in a small drop of test fluid. Microspot
      microarray technology, in combination with protein biomarkers and nucleic acid
      diagnostics, appears to be the future high-performance analytical platform of
      choice. Validation of a large number of disease markers in both molecular and
      protein diagnostics has paved the way for the emergence of the multiplex assay.
      Initially, simple low-throughput multiplex assays were tested using the
      immunoassay format. These were followed by low-level multiplexing and high
      throughput array-based immunoassays. More recently, two types of high-level
      multiplexing and high-throughput diagnostic methods using microspot arrays and
      bead arrays have been successfully developed to complement single-analyte assays.
      The value in rapid diagnostic evaluation for high-throughput multiplex,
      diagnostic test systems based on sound assay design must take into account data
      screening, normalization and statistical evaluation of possible concentration
      measurement, data errors and automated operation. Benefits of using multiplex
      array platforms include improved-quality patient care, as well as cost
      effectiveness and time saving. These multiplex methods also set the stage for
      future protein/nucleic acid codetection. Currently, the one analyte at a time
      test scheme is still dominant; nonetheless, the multiplex microspot microarray
      tests evaluated in a single multiassay analyzer are expected to become a
      significant part of clinical diagnostic testing within the next 5-10 years. This
      review is focused on microspot array and bead array methods for providing high
      throughput and a high degree of multiplexing in diagnostic testing.

PMID- 17187488
TI  - Stereotactic radiosurgery and radiation therapy for spinal tumors.
AB  - Spinal tumors constitute 15% of all CNS neoplasms. Radiation therapy can be
      administered for palliation of pain and spinal cord compression. However, the
      amount of radiation that can be administered is often limited by the tolerance of
      the spinal cord, especially in cases where prior radiation therapy has been
      given. Stereotactic radiosurgery and radiotherapy allow the delivery of a higher
      dose of radiation to spinal lesions, while limiting the spinal cord dose to below
      the tolerance level. These are technically demanding procedures and should be
      performed only when proper equipment and expertise are available. Data on spinal
      stereotactic radiosurgery and radiotherapy have emerged in recent years. This
      review summarizes the clinical applications of stereotactic radiosurgery and
      radiotherapy for spinal tumors.

PMID- 17187489
TI  - Integrated psychological therapy for schizophrenia patients.

PMID- 17187491
TI  - Spectrum of effectiveness of valproate in neuropsychiatry.
AB  - Valproate is principally effective in manic aspects of bipolar disorder.
      Tolerability has been somewhat more favorable for valproate than comparators,
      with the frequent adverse effects being gastrointestinal disturbances and weight
      gain. Total cholesterol and low-density lipoproteins are reduced by valproate.
      Valproate is effective and well tolerated when combined with lithium or
      antipsychotic drugs. Valproate is efficacious in mixed and euphoric mania. In
      studies of maintenance versus placebo and active comparators, patients initially
      treated with divalproex for mania had more robust long-term benefits than in the
      full sample analyses. In maintenance treatment, patients whose valproate serum
      levels were between 75 and 99 microg/ml had longer time to discontinuation for
      any reason or a new mood episode than did patients receiving placebo. The profile
      of utility in bipolar disorders is principally for core features of manic
      symptomatology (e.g., impulsivity, hyperactivity and irritability), with little
      evidence of benefit for anxiety or psychosis. Valproate appears useful in other
      disorders that have behavioral dimensions inclusive of the domains that valproate
      benefits in bipolar disorders, such as schizophrenia.

PMID- 17187492
TI  - Bupropion for weight reduction.
AB  - Bupropion is a norepinephrine and dopamine uptake inhibitor that has been
      available for several years for the treatment of depression and aiding smokers to
      quit. Although bupropion is not approved for treating obesity, three randomized
      clinical trials have shown some degree of efficacy for this drug in promoting
      weight loss in obese patients. The present drug profile provides a review of the
      pharmacology of bupropion, clinical evidence of efficacy with regard to weight
      reduction, tolerability and risks, and the current and future role of this drug
      in the management of obesity.

PMID- 17187493
TI  - University of Vermont update in dementia and neuropsychiatry. 15-17 September
      2006, Burlington, VT, USA.

PMID- 17187494
TI  - Schizophrenia: more evidence for less glutamate.
AB  - Evaluation of: Hahn CJ, Hoau-Yan W, Dan-Sung C et al. Altered neuregulin 1-erbB4
      signaling contributes to NMDA receptor hypofunction in schizophrenia. Nat. Med.
      12, 824-828 (2006). Schizophrenia may be associated with deficits in glutamate
      transmission at the N-methyl-D-aspartate (NMDA) receptor complex. Recent work has
      shown that neuregulin 1 (NRG1) acts via ErbB4 receptors to inhibit NMDA receptor
      currents. This is important given that NRG1 is a convincing susceptibility gene
      in schizophrenia. Hahn and colleagues add to our knowledge of NRG1 modulation of
      NMDA receptors and show intriguing differences between control and schizophrenic
      brains. NMDA receptors in the schizophrenic prefrontal cortex showed smaller
      responses to exogenously applied NMDA/glycine. Furthermore, NMDA receptors in
      tissue from schizophrenic patients appeared to be more sensitive to the
      inhibitory effects of a fixed dose of NRG1. In agreement, the ErbB4-PSD-95-NMDA
      complex was more tightly coupled in schizophrenic brains and NRG1-mediated
      stimulation of ErbB4 was markedly enhanced. These findings underscore the
      importance of NMDA receptors in schizophrenia and support therapeutic strategies
      aimed at boosting glutamate transmission.

PMID- 17187495
TI  - New challenges in family interventions for schizophrenia.
AB  - This review first outlines the rationale and research base supporting the
      development of family interventions for schizophrenia. The over-riding principles
      guiding effective family interventions for schizophrenia are then presented,
      along with the key components (engagement, assessment, education, communication
      skills training and problem-solving) shared by most family programs in
      schizophrenia. Meta-analyses demonstrating the efficacy of family interventions
      in reducing relapse and rehospitalization in schizophrenia are then discussed,
      along with issues regarding minimal duration of effective treatment, differential
      benefits of single and multiple family modalities and mixed evidence for the
      maintenance of treatment effects after termination. The benefits of participation
      in family-organized, nonprofessional support and education programs are then
      described. Finally, three issues meriting further study are outlined.

PMID- 17187496
TI  - Relationship between estrogen and schizophrenia.
AB  - There is a wealth of historical and circumstantial evidence to suggest that
      female patients with schizophrenia may suffer from a deficit in estrogenic
      function. The prolactin-inducing properties of most antipsychotic drugs, and
      subsequent negative feedback on estrogen levels, is in keeping with this. The
      functions of estrogen, its complex receptor organization and its numerous actions
      are the focus of ongoing research activity. Of particular interest are its
      neuroprotective properties, particularly with regard to cognitive impairment, and
      its involvement with neurotransmitter systems, which are the substrate for
      psychotropic drugs. Estrogen has now been used as an adjunct to standard
      antipsychotic medication in quite a few studies of female schizophrenia patients.
      However, most of these are not double-blind, randomized, controlled trials. Only
      two relatively small double-blind, randomized clinical trials returned positive
      results: one long-term study that selected for hypoestrogenism reported negative
      findings. Furthermore, recent evidence of the risks of long-term hormone
      replacement therapy is of concern. The advent of specific estrogen receptor
      modulators, which may avoid excess risks of cancer and cardiovascular events,
      will have little to add to schizophrenia treatment if estrogen is, essentially,
      devoid of any specific antipsychotic or adjuvant mechanism of action relevant to
      the pathophysiology of this disorder.

PMID- 17187497
TI  - Adherence to antidepressant treatment.
AB  - Depression is a common disorder with painful symptoms and, frequently, social
      impairment and decreased quality of life. The disorder has a tendency to be long
      lasting, often with frequent recurrence of symptoms. The risk of relapse and the
      severity of the symptoms may be reduced by correct antidepressant medication.
      However, the medication is often insufficient, both in respect to dosage and
      length of time. The reasons for incorrect medication are many, with lack of
      adherence to treatment being the most important. Although some patients taking
      antidepressant medication experience side effects, this may not be the most
      frequent reason for immature discontinuation of treatment. Other reasons for
      decreased adherence have been investigated in recent years. The patient's beliefs
      about the disorder and beliefs about antidepressants, including lack of
      conviction that the medication is needed and fear of dependence of antidepressant
      medicine, have a great influence on adherence to treatment.

PMID- 17187498
TI  - Vagus nerve stimulation for the treatment of depression and other
      neuropsychiatric disorders.
AB  - Vagus nerve stimulation is an interesting new approach to treating
      neuropsychiatric diseases within the class of brain-stimulation devices sometimes
      labeled 'neuromodulators'. With vagus nerve stimulation, a battery-powered
      generator implanted in the chest wall connects to a wire wrapped around the vagus
      nerve in the neck, and sends intermittent pulses of electricity along the nerve
      directly into the brain. This mechanism takes advantage of the natural role of
      the vagus nerve in conveying information into the brain concerning homeostatic
      information (e.g., hunger, chest pain and respirations). Vagus nerve stimulation
      therapy is US FDA approved for the adjunctive treatment of epilepsy and has
      recently been FDA approved for the treatment of medication-resistant depression.
      Owing to its novel route into the brain, it has no drug-drug interactions or
      systemic side effects. This treatment also appears to have high long-term
      tolerability in patients, with low rates of patients relapsing on vagus nerve
      stimulation or becoming tolerant. However, alongside the excitement and
      enthusiasm for this new treatment, a lack of Class I evidence of efficacy in
      treating depression is currently slowing down adoption by psychiatrists. Much
      more research is needed regarding exactly how to refine and deliver the
      electrical pulses and how this differentially affects brain function in health
      and disease.

PMID- 17187500
TI  - Role of CYP2D6 testing in selection of endocrine therapy for breast cancer.

PMID- 17187499
TI  - Regulators of G-protein-coupled receptor-G-protein coupling: antidepressants
      mechanism of action.
AB  - There is a significant gap between advances in medication for mental disorders
      and the present static situation of biological diagnosis and monitoring
      treatment. The system of neural transmission and signal transduction is a
      complicated, highly regulated cascade of biochemical events. Growing evidence
      suggests that receptor-G-protein coupling may be involved in both the
      pathogenesis and treatment of mood disorders. Our knowledge concerning the basic
      mechanisms underlying the phenomenon of desensitization, internalization,
      downregulation and resensitization of the G-protein-coupled receptor has been
      advanced during the last decade. The present review discusses the possible
      involvement of regulators of G-protein-coupled receptor-G-protein coupling: beta
      arrestins, G-protein-coupled receptor kinases and phosducin-like proteins, as
      well as beta-arrestins alternative signaling events, in the pathophysiology,
      diagnosis and treatment monitoring of mood disorders and in the mechanism of
      action of antidepressant medications.

PMID- 17187501
TI  - Epigenetic gene regulation: early environmental exposures.

PMID- 17187502
TI  - Spinal fluid biomarkers could provide protein 'bar code' allowing first
      diagnostic test for Alzheimer's disease.

PMID- 17187503
TI  - Graying anatomy? Toward molecular tumor characterization.
AB  - Will anatomical tumor classification become history as we make way for molecular
      characterization in oncology? Howard McLeod, Fred Eshelman Distinguished
      Professor of Pharmacy and Professor of Medicine at the University of North
      Carolina (NC, USA), is internationally recognized for his work on the
      pharmacogenomic analysis of cancer treatments. Here, he offers Pharmacogenomics
      his perspectives on the prospects for practical implementation of PGx in clinical
      care and the corresponding timescales. He and colleagues have already identified
      specific genetic components of several drugs that have lead to the US FDA
      changing the drug package inserts to identify patient groups that are genetically
      predisposed to risk of severe side effects or inadequate benefit. He is currently
      working with the large national clinical trials groups--such as Cancer and
      Leukemia Group B--to confirm that findings from small institutional studies will
      actually translate into better therapy across the USA.

PMID- 17187504
TI  - Oncology and pharmacogenetics in 2007.
AB  - Justin Stebbing is a member of the Royal College of Physicians, American Board of
      Internal Medicine and the Royal College of Pathologists. Originally, Justin
      trained in medicine at Trinity College Oxford (Oxford, UK), obtaining a triple
      first class degree. After completion of junior doctor posts in Oxford, he
      undertook a residency (junior doctor) training at The Johns Hopkins Hospital (MD,
      USA), before returning to London to continue his training in oncology at The
      Royal Marsden. Justin then undertook a PhD, funded by the medical research
      council, investigating the interplay between the immune system and cancer.
      Specifically, the role of heat shock proteins in tumorigenesis was examined,
      leading to the development of a cancer vaccine that is currently in clinical
      trials. Justin has published over 200 papers and book chapters, in journals such
      as the Lancet, New England Journal, Blood, the Journal of Clinical Oncology and
      Annals of Internal Medicine, the majority as first or last author. They mainly
      focus on early and late stage trials of new drugs, mechanisms of disease and
      prognostic indicators. He is on the editorial board of a number of journals and
      regularly serves as a referee. Justin's main focus is now in breast cancer, and
      helping patients with early and late stage disease get better.

PMID- 17187505
TI  - Cardiovascular therapy and pharmacogenetics in 2007.
AB  - John Carlquist received a PhD from the Department of Cellular Viral and Molecular
      Biology at the University of Utah School of Medicine (UT, USA) with research
      emphasis in molecular immunology. After completion of his training, he received a
      faculty appointment in the Department of Internal Medicine, University of Utah,
      where he became interested in immune mechanisms in cardiovascular disease. He
      developed an interest in genetics through studies of human leukocyte antigen
      (HLA) associations with idiopathic dilated cardiomyopathy and rheumatic heart
      disease. He began the Molecular Diagnostics Laboratory for Intermountain
      Healthcare and continues to serve as Technical Director; he also directs the
      Intermountain Heart Study Molecular and Genetic Research Laboratory. Current
      research interests include the genetics of lipid metabolism as related to
      coronary heart disease and the genetic factors influencing drug treatment
      outcomes.

PMID- 17187506
TI  - HIV and pharmacogenomics in 2007.
AB  - Saye Khoo is Reader in the Department of Pharmacology at the University of
      Liverpool (UK), having graduated from the University of London in 1985. He is
      Honorary Consultant in Infectious Diseases, and is lead clinician for the Royal
      Liverpool University Hospital, and the Mersey, Cheshire & North Wales HIV Managed
      Care Network. Khoo has also served in the BHIVA Treatment Guidelines Writing
      committee, PENTA Pharmacology committee, and as an editor for the Journal of
      Antimicrobial Chemotherapy. Research interests include assessment of
      intracellular accumulation of HIV drugs, role of drug transporters, evolution of
      HIV resistance within drug sanctuary sites, drug-drug interactions, therapeutic
      drug monitoring and pharmacogenomics of HIV therapy. Similar work is also in
      progress with TB drugs in regard to sterilizing activity.

PMID- 17187508
TI  - Pharmacogenetic study of methylenetetrahydrofolate reductase and thymidylate
      synthase in Japanese and assessment of ethnic and gender differences.
AB  - OBJECTIVES: We investigated the four polymorphisms of the 5,10
      methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genes
      that are related to the pharmacologically active sites of methotrexate for the
      treatment of rheumatoid arthritis in 102 healthy Japanese adults and assessed the
      possibility of ethnic and gender differences. METHODS: Polymorphisms of MTHFR
      C677T, A1298C, the two or three 28-bp tandem repeats in the TYMS 5'-untranslated
      regions (UTR), and the 6-bp deletion/insertion in the TYMS 3'-UTR were measured
      using polymerase chain reaction with restriction fragment length polymorphism
      method. Published data on allelic frequencies by ethnic group and gender were
      collected from Medline. RESULTS: Allelic frequencies in healthy Japanese adults
      were: MTHFR 677T allele 41%, MTHFR 1298C allele 22%, TYMS 5'-UTR 3R allele 84%,
      and TYMS 3'-UTR-6-bp allele 59%. Significant differences were found in the
      distribution of MTHFR C677T between black and Japanese populations, of TYMS 5'
      UTR alleles between Caucasian or black and Japanese populations, and of TYMS 3'
      UTR alleles between Caucasian and Japanese populations (p < 0.001). Moreover, a
      gender difference was found in TYMS 3'-UTR allelic frequency in Japanese (p =
      0.015). CONCLUSION: Ethnic and gender variations in the distribution of these
      allelic frequencies may associate with the difference in the effects of
      methotrexate in rheumatoid arthritis patients.

PMID- 17187507
TI  - Ethnicity-related polymorphisms and haplotypes in the human ABCB1 gene.
AB  - INTRODUCTION: The human multidrug resistance gene ATP-binding cassette B1 (ABCB1)
      codes for P-glycoprotein (P-gp), an important membrane-bound efflux transporter
      known to confer anticancer drug resistance as well as affect the pharmacokinetics
      of many drugs and xenobiotics. A number of single nucleotide polymorphisms (SNPs)
      have been identified throughout the ABCB1 gene that may have an effect on P-gp
      expression levels and function. Haplotype as well as genotype analysis of SNPs is
      becoming increasingly important in identifying genetic variants underlying
      susceptibility to human disease. Three SNPs, 1236C-->T, 2677G-->T and 3435C-->T,
      have been repeatedly shown to predict changes in the function of P-gp. The
      frequencies with which these polymorphisms exist in a population have also been
      shown to be ethnically related. METHODS: In this study, 95 individuals
      representative of the entire ethnic make-up of the USA were compared with 101
      individuals from an Ashkenazi-Jewish population. These individuals were analyzed
      by genomic sequencing and polymerase chain reaction, using restriction fragment
      length polymorphisms, to calculate their genotype frequencies. RESULTS: A total
      of 25 SNPs were located in the exons of the ABCB1 gene. All of the polymorphisms
      identified were in parts of the ABCB1 gene product predicted to be intracellular,
      and 16 appear to be novel as compared with those listed by the National Center
      for Biotechnological Information. Frequencies of the 1236C-->T and 2677G-->T/A/C
      SNPs were similar for the US and Ashkenazi populations (64.2 and 60.4%,
      respectively for 1236C-->T [chi2: 0.30; p < or = 1]; 55.8 and 64.4%, respectively
      for 2677G-->T/A/C [chi2: 1.49; p < or = 1]), but were different for 3435C-->T
      (24.2% for the US population and 69.3% for the Ashkenazi population [chi2:
      39.927; p < or = 0.001]). The 1236T/ 2677T/3435T haplotype occurred in 23.6%
      (standard error: 0.013) of the Ashkenazi population. CONCLUSION: The SNP at
      location 3435C-->T plays a significant role in the ABCB1 gene. The haplotype and
      genotype analysis from these data may be used as a basis for studies on the
      relationship between ABCB1 genotypes and drug efficacy, drug toxicity, disease
      susceptibility or other phenotypes.

PMID- 17187509
TI  - Vascular endothelial growth factor pharmacogenetics: a new perspective for anti
      angiogenic therapy.
AB  - The pharmacogenetic approach to anti-angiogenic therapy should be considered a
      possible strategy for many pathological conditions with high incidence in Western
      countries, including solid tumors, age-related macular degeneration or
      endometriosis. While pharmacogenetic studies are building stronger foundations
      for the systematic investigations of phenotype-genotype relationships in many
      research and clinical fields of medicine, pharmacogenetic data regarding anti
      angiogenic drugs are still lacking. Here we review preclinical and clinical
      genetic studies on angiogenic determinants such as vascular endothelial growth
      factor and vascular endothelial growth factor receptor-2. We suggest that
      pharmacogenetic profiling of patients who are candidates for the currently
      available anti-angiogenic agents targeting vascular endothelial growth factor and
      vascular endothelial growth factor receptor-2 may aid the selection of patients
      on the basis of their likelihood of responding to the drugs or suffering from
      toxicity.

PMID- 17187510
TI  - The genetics of fibromyalgia syndrome.
AB  - Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly
      affecting women. Although the etiology of FMS is not completely understood,
      varieties of neuroendocrine disturbances, as well as abnormalities of autonomic
      function, have been implicated in its pathogenesis. The exposure of a genetically
      predisposed individual to a host of environmental stressors is presumed to lead
      to the development of FMS. Fibromyalgia overlaps with several related syndromes,
      collectively compromising the spectrum of the functional somatic disorder. FMS is
      characterized by a strong familial aggregation. Recent evidence suggests a role
      for polymorphisms of genes in the serotoninergic, dopaminergic and
      catecholaminergic systems in the etiopathogenesis of FMS. These polymorphisms are
      not specific for FMS and are similarly associated with additional comorbid
      conditions. The mode of inheritance in FMS is unknown, but it is most probably
      polygenic. Recognition of these gene polymorphisms may help to better subgroup
      FMS patients and to guide a more rational pharmacological approach. Future
      genetic studies conducted in larger cohorts of FMS patients and matched control
      groups may further illuminate the role of genetics in FMS.

PMID- 17187511
TI  - Pattern-recognition techniques with haplotype analysis in pharmacogenomics.
AB  - Single nucleotide polymorphisms (SNPs) can be used in clinical association
      studies to determine the contribution of genes to drug efficacy. However, it
      would be extremely inefficient to test all the 10 million common SNPs for an
      association study. Here we review haplotype analysis and pattern-recognition
      techniques to systematically select candidate SNPs for candidate-gene association
      studies in pharmacogenomics. First, we survey linkage disequilibrium methods to
      identify tag SNPs and explore the use of haplotypes as genetic markers that are
      correlated and associated with drug efficacy. Secondly, we investigate pattern
      recognition algorithms and statistical analyses to assess drug efficacy based on
      SNPs and other factors. Finally, we study pattern-recognition approaches to
      evaluate the epistasis among genes and SNPs. These techniques may provide tools
      for clinical association studies and help find genes/SNPs involved in responses
      to therapeutic drugs or adverse drug reactions.

PMID- 17187512
TI  - From molecular diagnostics to personalized testing.
AB  - Gene-based molecular diagnostics is changing the practice of medicine and will
      continue to do so for the foreseeable future. The major underlying principle of
      these diagnostic tests is the use of specific nucleic acid sequences as
      surrogates; amplification of the surrogate markers enables the detection of
      pathogens or disease-related gene mutations. Gene targets can be amplified by
      target-, probe- or signal-based methods. Combined use of nucleic acid
      amplification and enzyme-linked immunosorbent assay with methods such as immuno
      polymerase-chain reaction allows us to detect protein at femtogram (10(15) g)
      levels. A variety of choices are available for the detection of amplified
      amplicons with the fluorophore-linked nanoparticles as the most sensitive
      markers. The unique advantages of using covalently-linked nanoparticles include
      the detection of single molecules, the ability to enrich molecules of interest
      with unprecedented detection sensitivity (up to zeptogram levels, 10(21) g) and
      the flexibility of multiple functionalization. Automation appears to be the
      current trend for high-volume molecular testing of infectious diseases. Molecular
      profiling of various diseases using genomic or proteomic approaches opens up a
      molecule wonderland with promise and emergence of new molecular testing that will
      likely impact the practice of medicine to a greater degree in the future. The
      future of molecular-based testing and the journey toward personalized testing
      will be discussed.

PMID- 17187513
TI  - Predicting risk of breast cancer recurrence using gene-expression profiling.
AB  - The molecular profiling of breast tumors using the powerful microarray technology
      has uncovered the molecular heterogeneity of breast tumors and has offered novel
      insight into breast tumorigenesis. The estrogen receptor (ER) has been shown to
      be the most important discriminator dichotomizing breast cancer into two main
      subsets. At the same time, proliferation, as captured by the recently developed
      Genomic Grade Index (GGI) has been found to be the most important prognostic
      factor in breast cancer, far beyond ER status. Interestingly, this index
      encompasses a significant portion of the predictive power of many published
      prognostic signatures. The challenge now is to integrate all the prognostic gene
      signatures available to date towards a comprehensive genomic fingerprint of the
      primary tumor. In the future, we should be able to offer individualized treatment
      to our patients based on a clinical decision-making algorithm that takes into
      account the clinicopathological parameters, the genomic profile of the primary
      tumor, the presence of micrometastatic cells and pharmacogenetic data for drug
      response.

PMID- 17187514
TI  - Epidermal growth factor receptor as a target for cancer therapy.

PMID- 17187516
TI  - Denileukin diftitox: a biotherapeutic paradigm shift in the treatment of lymphoid
      derived disorders.
AB  - Denileukin diftitox (Ontak) represents an example of a fused molecule that
      targets cells bearing high affinity interleukin-2 receptors internalized via
      receptor-mediated endocytosis in an acidified vesicle. Denileukin diftitox is
      proteolytically cleaved within the endosome liberating the enzymatically active
      portion of the diphtheria toxin, the A fragment. Diphtheria toxin fragment A is
      released into the cytosol inhibiting the protein synthesis through the ADP
      ribosylation of the elongation factor-2, and leading to cell death. This review
      focuses on the clinical trials that led to the FDA approval of the drug for
      cutaneous T cell lymphoma in the US, and investigational studies demonstrating
      drug-activity against B and T-cell non-Hodgkin's lymphoma, chronic lymphocytic
      lymphoma and acute graft versus disease within allogeneic hematopoietic stem cell
      transplant.

PMID- 17187517
TI  - 7th meeting of the International Society of Geriatric Oncology. November 2-4,
      2006, Kurhaus Hotel, Scheveningen, The Netherlands.

PMID- 17187518
TI  - Treatment of sporadic nonmedullary thyroid carcinomas in pediatric age.
AB  - Nonmedullary thyroid carcinomas are rare malignancies in pediatric ages. The vast
      majority of them are papillary carcinomas with an overall survival of
      approximately 100%. Their outcome is independent of strong prognostic factors of
      adults, such as papillary carcinoma histological subtype, invasion into soft
      tissue of the neck, presence and site of distant metastases, relapse and type of
      surgery. In these ages, follicular carcinomas and poorly differentiated
      carcinomas are exceptional. Undifferentiated (anaplastic) carcinomas are
      practically absent. In most institutions, the therapy of choice for all pediatric
      thyroid carcinomas is the radical approach, aimed at the eradication at diagnosis
      of all clinical and subclinical neoplastic foci, both at thyroid, lymph node and
      distant level. It consists of total thyroidectomy and lymphadenectomy in children
      with clinically evident lymph-node metastases, followed by radioactive iodine
      therapy independent of histotype and stage. Recently, owing also to the high
      sensitivity to hormonal manipulation shown by pediatric papillary carcinomas, a
      conservative approach has been proposed for selected cases, consisting of the
      removal of only the grossly detectable disease followed by thyroid-stimulating
      hormone-suppressive hormonal therapy to control subclinical disease. Today, the
      existence of two therapeutic approaches, radical versus conservative therapy,
      should be considered whenever treating a child or adolescent with a nonmedullary
      thyroid carcinoma. Not least, permanent post-treatment complications of radical
      surgery and radioactive iodine therapy should be taken into account. The future
      tasks include the stratification of thyroid carcinomas into low- and high-risk
      cases, also including their molecular alterations and the possibility of a
      molecularly targeted therapy against tyrosine kinases involved in the
      pathogenesis of thyroid carcinomas.

PMID- 17187519
TI  - Adult human sarcomas. I. Basic science.
AB  - When connective tissue undergoes malignant transformation, glioblastomas and
      sarcomas arise. However, the ancient biochemical mechanisms, which are now
      operational in sarcomas distorted by mutations and gene fusions in misaligned
      chromosomes, were originally acquired by those cells that emerged during the
      Cambrian explosion. Preserved throughout evolution up to the genus Homo, these
      mechanisms dictate the apoptosis- and senescence-resistant immortality of
      malignant cells. A 'retroviral paradox' distinguishes human sarcomas from those
      of the animal world. In contrast to the retrovirally induced sarcomatous
      transformation of animal (avian, murine, feline and simian) cells, human sarcomas
      have so far failed to yield a causative retroviral isolate. However, the proto
      oncogenes/oncogenes transduced from their host cells by retroviruses of animals
      are the same that are active in human sarcomas. Since the encoded oncoproteins
      arise after birth, they are recognized frequently by the immune system of the
      host. Immune lymphocytes that kill autologous sarcoma cells in vitro commonly
      fail to do so in vivo. Sarcoma vaccines generate immune T- and natural killer
      cell reactions; even when vaccinated patients do not show a clinical response,
      their tumors become more sensitive to chemotherapy. The aim of this review is to
      lay a solid molecular biological foundation for the conclusion that targeting the
      sarcoma oncogenes will result in regression of the disease.

PMID- 17187520
TI  - New drug therapies for advanced renal cell carcinoma.
AB  - The incidence of renal cell cancer is increasing and surgery is the only curative
      treatment for patients presenting with localized disease at diagnosis. The
      treatment of metastatic renal cell cancer is palliative and, until recently,
      immunotherapy has been the standard treatment approach with response rates
      between 10 and 20%. An increase in the appreciation of the biology of this
      disease has resulted in a number of new 'targeted' therapies being developed.
      Most notable is the introduction of tyrosine kinase inhibitors with significant
      activity in both treatment-naive and cytokine-refractory renal cell cancer. Drugs
      targeting angiogenic pathways also appear promising. These agents are being
      rapidly introduced into clinical practice, but further studies are needed to
      establish their optimal place in the management of renal cell cancer and, in
      particular, the role of combination and/or sequential therapy.

PMID- 17187521
TI  - Presurgical therapy in metastatic renal cell carcinoma.
AB  - The standard approach for managing patients with metastatic renal cell carcinoma
      consists of a cytoreductive nephrectomy followed by immunotherapy, chemotherapy
      or a targeted agent. Optimal timing of surgery and systemic therapy is not known,
      and has not been researched. A number of questions arise. First, in the era of
      antivascular therapy, is cytoreductive nephrectomy a necessity? Second, is it
      possible that pretreatment with systemic therapy prior to cytoreductive
      nephrectomy improves surgical outcome and survival? Third, which agents are best
      suited for an integration of surgery with systemic therapy, both in the
      metastatic and the nonmetastatic setting? This review will address each of these
      questions and summarize ongoing trials that are designed to provide some of the
      answers.

PMID- 17187522
TI  - Update on therapy for melanoma: opportunities for patient selection and
      overcoming tumor resistance.
AB  - The incidence of malignant melanoma is rising faster than any other malignancy.
      Although earlier stage patients can be cured with surgical resection with or
      without adjuvant therapy, a significant number of patients go on to develop
      disseminated disease. Currently, limited therapeutic options exist for patients
      with metastatic melanoma. Recent studies suggest that patient selection is
      feasible and may enable the restriction of treatment to those most likely to
      benefit. Additionally, several potential mechanisms of tumor resistance have been
      identified creating opportunities for circumventing them. This article will
      review current strategies for patient selection and overcoming therapeutic
      resistance. These strategies hold the promise of extending the clinical benefits
      of current therapies as well as facilitating the development of additional and
      more active treatments.

PMID- 17187527
TI  - Hospice and palliative medicine goes mainstream.

PMID- 17187523
TI  - Review of image-guided radiation therapy.
AB  - Image-guided radiation therapy represents a new paradigm in the field of high
      precision radiation medicine. A synthesis of recent technological advances in
      medical imaging and conformal radiation therapy, image-guided radiation therapy
      represents a further expansion in the recent push for maximizing targeting
      capabilities with high-intensity radiation dose deposition limited to the true
      target structures, while minimizing radiation dose deposited in collateral normal
      tissues. By improving this targeting discrimination, the therapeutic ratio may be
      enhanced significantly. The principle behind image-guided radiation therapy
      relies heavily on the acquisition of serial image datasets using a variety of
      medical imaging platforms, including computed tomography, ultrasound and magnetic
      resonance imaging. These anatomic and volumetric image datasets are now being
      augmented through the addition of functional imaging. The current interest in
      positron-emitted tomography represents a good example of this sort of functional
      information now being correlated with anatomic localization. As the
      sophistication of imaging datasets grows, the precise 3D and 4D positions of the
      target and normal structures become of great relevance, leading to a recent
      exploration of real- or near-real-time positional replanning of the radiation
      treatment localization coordinates. This 'adaptive' radiotherapy explicitly
      recognizes that both tumors and normal tissues change position in time and space
      during a multiweek course of treatment, and even within a single treatment
      fraction. As targets and normal tissues change, the attenuation of radiation
      beams passing through these structures will also change, thus adding an
      additional level of imprecision in targeting unless these changes are taken into
      account. All in all, image-guided radiation therapy can be seen as further
      progress in the development of minimally invasive highly targeted cytotoxic
      therapies with the goal of substituting remote technologies for direct contact on
      the part of an operator or surgeon. Although data demonstrating clear-cut
      superiority of this new high-tech paradigm compared with more conventional
      radiation treatment approaches are scant, the emergence of preliminary data from
      several early studies shows that interest in this field is broad based and
      robust. As outcomes data accumulate, it is very likely that this field will
      continue to expand greatly. Although at present most of the work is being
      performed at major academic centers, the enthusiastic adoption of many of the
      devices and approaches being developed for this field suggest a rapid penetration
      into the community and the use of the technology by teams of specialists in the
      fields of radiation medicine, radiation physics and various branches of surgery.
      A recent survey of practitioners predicted very widespread adoption within the
      next 10 years.

PMID- 17187529
TI  - Palliative care in inpatient units.

PMID- 17187531
TI  - Colorado revised statutes in support of palliative care limiting criminal
      liability.
AB  - Colorado's manslaughter law classifies assisted suicide as a felony. Because
      terminal patients are close to life's end, death while being treated is
      inevitable, therefore, there was concern among physicians that the fear of
      prosecution continued to prevent adequate pain relief for terminal patients. A
      group of physicians and concerned citizens set out to amend Colorado Revised
      Statutes to reassure doctors and others prescribing or administering palliative
      care for terminal patients that they would not be indicted under the law
      prohibiting assisted suicide. The 2006 Assembly passed the amendment (quoted in
      the text) with virtually no opposition in either house and it was signed into law
      by the governor, effective July 6, 2006. Note that in addition to allowing
      appropriate pain management, it specifically emphasizes that it does not permit
      assisted suicide.

PMID- 17187530
TI  - Enhanced analgesia with opioid antagonist administration.
AB  - BACKGROUND: Pain, not responsive to opioid analgesics, remains a problem for
      patients with chronic and cancer pain as well as their families, and clinicians.
      Opioid antagonists have various uses in pain and palliative care. Their use in
      the reversal of tolerance and hyperalgesia remains at the basic science level and
      has limited clinical exposure. OBJECTIVE: To improve symptom control and quality
      of life in patients with pain not responsive to opioid analgesics. DESIGN:
      Present three cases in which patients have undergone administration of opioid
      antagonists for the purpose of analgesia. METHODS: Patients on opioids analgesics
      received parenteral opioid antagonist, naloxone. Complete withdrawal under a
      sedative or conscious sedation was allowed and then the opioid at smaller doses
      was restarted and analgesia was observed. RESULTS: All patients had improved
      analgesia on a significantly lower dose of opioid analgesics. CONCLUSIONS: Only
      three patients who have received this procedure were presented yet all have
      responded positively to this procedure. Further research is needed to elucidate
      the mechanism and clinical relevance in the acute use of opioid antagonists.

PMID- 17187532
TI  - A case of serotonin syndrome and mutism associated with methadone.
AB  - A patient was seen on the palliative care service at our institution who
      developed serotonin syndrome and mutism associated with methadone use. Serotonin
      syndrome is often described as a clinical triad of mental status changes,
      autonomic hyperactivity, and neuromuscular abnormalities, but not all of these
      findings are consistently present in all patients with the disorder. The
      incidence of the serotonin syndrome is thought to mirror the increasing number of
      proserotonergic agents being used in clinical practice. In 2002, the Toxic
      Exposure Surveillance System, which receives case descriptions from office-based
      practices, inpatient settings, and emergency departments, reported 26,733
      incidences of exposure to selective serotonin-reuptake inhibitors (SSRIs) that
      caused significant toxic effects in 7349 persons and resulted in 93 deaths.
      Serotonin syndrome is not an idiopathic drug reaction; it is a predictable
      consequence of excess serotonergic agonism of central nervous system (CNS)
      receptors and peripheral serotonergic receptors. The myriad of symptoms with
      which serotonin syndrome may present is compounded by the fact that more than 85%
      of physicians are unaware of serotonin syndrome as a clinical diagnosis. Other
      SSRIs such as fluoxetine and fluvoxamine have been shown to increase methadone
      plasma concentrations in dependent patients. Although the exact mechanism is
      unknown, there are several pathways via which a significant interaction could
      occur. This would include the effects methadone has on N-methyl-D-aspartate
      (NMDA) in addition to the impact of methadone on the cytochrome P450 enzyme
      system. The mainstay of treatment of serotonin syndrome is withdrawal of the
      offending agent and supportive care. These actions resulted in resolution of our
      patient's symptoms. Serotonin syndrome is becoming more common, and with the
      utilization of polypharmacy on many palliative care services should be considered
      as unifying differential diagnosis in the appropriate setting.

PMID- 17187533
TI  - Deaths in an academic medical center.
AB  - The number of inpatient deaths in a calendar year in an academic medical center
      was reviewed from a computerized database. The total number was 1222. The median
      length of hospital stay for those who died was 7 days (range, 1-190); 404 (33%)
      were 75 years or older. There were 678 (55%) males and 544 (45%) females. The
      pulmonary medicine service had the most deaths with 290 (24%) followed by
      hematology/oncology 230 (18%). The most common primary diagnoses in the decedents
      were subendocardial infarction 58 (5%), congestive heart failure 57 (5%), and
      pneumonia 45 (4%). The most common diagnostic-related groups (DRGs) were
      respiratory system disorders (475), 98 (8%); tracheostomy (483), 75 (6%); and
      heart surgery (110), 65 (5%). Frequent procedures done prior to death were
      mechanical ventilation (<96 hours) 101 (8%), and mechanical ventilation (>96
      hours) 55 (5%), and tracheostomy 54 (4%). Invasive procedures were common. Forty
      five percent of the predeath patient days were spent in intensive care units.
      Palliative medicine was involved in the care of 20% of all the decedents.

PMID- 17187534
TI  - Ovarian cancer and ascites: A questionnaire on current management in the United
      kingdom.
AB  - A questionnaire on ovarian cancer ascites management was sent to members of the
      British Gynaecological Cancer Society (BGCS), the National Gynaecological
      Oncology Nurses, and the Assoication of Palliative Medicine. Questions were asked
      on diuretics, hematologic investigations, paracentesis, and duration of stay.
      Nine hundred ninety-five questionnaires were distributed, of which 492 replies
      were received (49% response rate). Fifty-five percent of responders used
      paracentesis as first-line management of ovarian cancer ascites (15% diuretics).
      Seventy-five percent performed some blood tests in relation to paracentesis.
      Ultrasound was used by 43.6% during paracentesis (15.7% for direct visualization,
      27.9% to mark an entry site). Seventy-seven percent used a Bonanno catheter.
      Eighty-three percent used no intravenous fluids during paracentesis, and there
      was a wide variation in the amount and rate of drainage of ascites (1 L maximum
      up to free drainage of all ascites, median 5 L; 0.5 L per hour to free drainage).
      Gynecologists tended to use more interventions (paracentesis, ultrasound, and
      intravenous fluids) than palliative care physicians or medical oncologists, while
      palliative care physicians used fewer interventions but admitted patients for
      longer periods of time. This identified several areas for future study: the value
      of hematologic investigations, the use of outpatient management for paracentesis,
      and the use of ultrasound and the rate of drainage of ascites.

PMID- 17187535
TI  - General practitioners' attitudes to palliative care: A Western Australian rural
      perspective.
AB  - BACKGROUND: People with a terminal illness and their families who live in rural
      or remote areas of Australia face difficulties in accessing palliative care
      services as a result of physical isolation. This leads to rural general
      practitioners (GPs) carrying the burden of care, which is often exacerbated by a
      lack of support staff. OBJECTIVE: This research addressed the following
      questions: What are GPs' attitudes to palliative care in a rural center of
      Western Australia? What factors contribute to GPs' attitudes to palliative care
      in a rural center of Western Australia? What are the perceived barriers to the
      provision of palliative care in a rural center of Western Australia? DESIGN: A
      qualitative in-depth research design was used for this study due to the
      exploratory nature of the research. A model of attitudes that considers an
      attitude as a summary evaluation of an issue based on: cognitive information,
      (thoughts and beliefs), affective or emotional information, and information
      concerning behavior, was used. PARTICIPANTS: Participants were 10 registered GPs
      located within the Greater Bunbury Division of General Practice in Western
      Australia. RESULTS: Six themes emerged from the research: maintaining patients'
      quality of life, providing continuity of care, experiencing emotional issues,
      collaborating with a multidisciplinary team, acknowledging the need for education
      and training, and dealing with the wider context. CONCLUSION: Education and
      training for rural GPs needs to be relevant to the local context and needs to
      focus on emotions and beliefs.

PMID- 17187536
TI  - When the spirit leaves: Childhood death, grieving, and bereavement in Islam.
AB  - The death of a child has a profound and often long-lasting impact on families.
      The parent's relationship and their ability to bond with and take care of
      surviving children may be affected. It is important for healthcare workers to
      understand the dynamics associated with bereavement, especially when the family
      comes from a non-Western culture. Islam is one of the three most populous
      religions along with Christianity and Hinduism and the fastest growing religion
      in the United States but remains largely misunderstood. This paper seeks to
      explain what Islam is, who is a Muslim, where they live, and what they believe
      and practice. It also explains how Islamic beliefs contextualize the meaning of
      life and death for Muslims and how they are exhorted to grieve upon a child's
      death. Reading this paper will enable those who care for Muslim families to
      better attend to the social and emotional needs of Muslim parents and siblings
      after such a tragic event.

PMID- 17187537
TI  - Access to home-based hospice care for rural populations: Identification of areas
      lacking service.
AB  - BACKGROUND: Many persons dying of cancer enroll in home-based hospice prior to
      death. It is established in the literature that persons in rural settings are
      less likely to use hospice than persons living in urban areas. We examine whether
      this is due, in part, to a lack of hospice providers serving rural areas.
      METHODS: The 100% Medicare enrollment and hospice files for 2000-2002 were the
      basis for this study. We used a Bayesian smoothing technique to estimate the ZIP
      code-level service area for each Medicare-certified hospice in the United States.
      These service areas were combined to identify ZIP codes not served by any
      hospice. RESULTS: Overall, approximately 332,000 elders (7.5% of ZIP codes)
      reside in areas not served by home-based hospice. Each year over 15,000 deaths
      occur in these unserved areas. There was a strong association between lack of
      service and urban/rural gradient. One hundred percent of the ZIP codes in the
      most urban areas (>1,000,000 people) are served by hospice and only 2.8% of the
      ZIP codes in urban areas of less than 1,000,000 are unserved. In rural areas
      adjacent to urban areas, over 9% of ZIP codes are unserved and in rural areas not
      adjacent to an urban area almost 24% of ZIP codes are not served by hospice.
      CONCLUSIONS: While the majority of the elderly population of the US resides in
      areas currently served by Medicare-certified hospice, there is a geographically
      large area that lacks home-based hospice services. Current payment policies may
      need to be adjusted to facilitate hospice availability to these rural
      populations.

PMID- 17187538
TI  - Bereaved hospice caregivers' perceptions of the end-of-life care communication
      process and the involvement of health care professionals.
AB  - BACKGROUND: This study was conducted to gain an understanding of bereaved hospice
      family caregivers' perceptions of the communication process from initial
      discussion of the need for end-of-life care and hospice through the decision to
      choose hospice and the transition home. METHODS: One hundred eight bereaved
      hospice caregivers that were 36 months postpatient death responded to a
      quantitative mailed survey. Aspects of the end-of-life care communication
      process, including involvement of health care professionals at each step, were
      assessed. RESULTS: Serious illness and the need for hospice care were first
      mentioned to patients and caregivers by physicians. Often the caregivers recalled
      only one meeting in which hospice was discussed. Other than the physicians,
      social workers were the professionals most often present in at least one of these
      meetings. Nurses and social workers were both perceived to be helpful in the
      transition to home hospice. Social workers were reported to be most comfortable
      with discussion of end-of-life care, most knowledgeable, and most available
      during the communication process that led to a decision about end-of-life care.
      Suggestions that these caregivers had to improve communication with health care
      professionals were categorized from responses to an open-ended survey question
      as: the need to discuss vital information earlier and what to expect for care at
      end stage; be more forthcoming about reality of death; and treat people as
      individuals. CONCLUSIONS: Although many health care professionals play a role in
      the communication and transition to hospice care, physicians and social workers
      were found to be pivotal participants in this process. A coordinated team
      approach to end-of-life communication and decision-making may facilitate the
      process and possibly lead to increased and earlier referral to hospice.

PMID- 17187539
TI  - Advanced illness index: Predictive modeling to stratify elders using self-report
      data.
AB  - OBJECTIVES: Develop a prediction model to identify persons who have an increased
      risk of dying within the next 36 months, in order to focus additional resources
      and assessment in areas related to advanced care planning. DESIGN: Retrospective
      study with a 3-year observation period. SETTING: Integrated, not-for-profit
      managed care organization. PARTICIPANTS: Beneficiaries aged 65-105 responding to
      an annual survey (n = 4888). MEASUREMENTS: Survey instrument includes physical
      function, geriatric syndromes, health care utilization, special equipment use,
      self-care deficits, caregiving responsibilities, and general health problems.
      RESULTS: An 11-variable model changed the baseline chi2 from 315.71 (df = 1) to
      742.511 (df = 11). The percent of subjects correctly classified was 74.3% and the
      negative predictive value was 92.2%. CONCLUSION: Advanced Illness Index (AII)
      model is stable. Characteristic variables used are not easily reversed: the 1997
      cohort classified as at-risk consistently remained at risk or died in the
      subsequent years (1998, 92%; and 1999, 96%) and 92% of those not at-risk survived
      the next 36 months. Persons at high risk should at a minimum be made aware of the
      types of integrated home and community-based services available to them should it
      be needed. They also should be targeted for elicitation of treatment preferences,
      values, designation of health care proxy, planning, and advanced care directives.

PMID- 17187540
TI  - The effect of a web-based, patient-directed intervention on knowledge,
      discussion, and completion of a health care proxy.
AB  - OBJECTIVES: To examine the effect of patient-directed electronic messages on
      health care proxy (HCP) use. DESIGN: Randomized control trial using an electronic
      message intervention to encourage patients to complete an HCP document. SETTING:
      General medical practice at a large tertiary care teaching institution.
      PARTICIPANTS: Nine hundred twelve patients aged older than 50. MEASUREMENTS: We
      reviewed online medical records (OMRs) to assess for discussion and documentation
      of HCPs and to collect information on patient characteristics. We surveyed
      participants to determine knowledge, discussion, and completion of HCPs. RESULTS:
      Four hundred thirty participants were randomized to the intervention group and
      482 to the control group. Only 1 HCP discussion (intervention group) and only 10
      new HCPs (4 in intervention group versus 6 in control group, p = 0.649) were
      documented in the OMR. Among the 444 survey responders, 205 (46%) reported having
      an HCP, but only 74 (36%) of these had discussed the HCP with their doctors and
      only 9 (4%) had a documented HCP in the OMR. Patients in the intervention group
      were more likely to report knowledge of HCPs (adjusted risk ratio [RR] 1.07; 95%
      confidence interval [CI], 1.01-1.14) and having a plan to complete one in the
      future (adjusted RR 1.19; 95% CI, 1.05-1.36). CONCLUSION: This patient-directed
      intervention did not increase patient completion of an HCP but was associated
      with greater knowledge of an HCP and planning to complete one.

PMID- 17187541
TI  - Parents' reactions to participating in interviews about end-of-life decision
      making.
AB  - BACKGROUND: Although in-depth interviewing is well suited to studying the
      sensitive topic of end-of-life decision making, no reports have been published
      assessing the effects on parents of participating in interviews regarding end-of
      life decision making for critically ill children. OBJECTIVE: To examine the
      reactions of pediatric intensive care unit (PICU) patients' parents to interviews
      on end-of-life decision making for their child. METHODS: We conducted
      semistructured interviews on end-of-life decision making with PICU patients'
      parents from two tertiary care PICUs. We approached 117 parents of 102 patients.
      Seventy-four parents (63%) of 69 patients participated. RESULTS: Forty-three
      parents (61%) described the interview as "a good experience," 20 (29%) as "a
      neutral experience," and 1 (1%) as "a bad experience." The parent who judged the
      interview negatively stated that, "It bothers me a little bit because my son is
      [out] there having difficulties and I'm in here and not out there." Fifty-four of
      59 parents (92%) said they would participate in another similar interview. Most
      parents (92%) felt the medical community should continue research on end-of-life
      decision making. Themes identified from the responses included: emotional
      reaction to the interviews; exposure to end-of-life decision-making issues;
      impact on parents' views; and impact on future end-of-life decision making.
      Parents' comments suggested that many perceived the interviews as beneficial.
      CONCLUSIONS: This study demonstrates the willingness of many parents of
      critically ill children to participate in study interviews regarding end-of-life
      decision making, a topic that most parents felt was important and warranted more
      research.

PMID- 17187542
TI  - Ideals and compromises in palliative care.
AB  - This qualitative study explores the concept of ideal palliative care as it
      broadens its field of application from terminal care to include people earlier in
      the course of an illness. Focus groups were held with palliative care
      professionals from community, inpatient, and hospital consultancy services to
      examine this issue. Palliative care professionals have clear views of what
      constitutes ideal care that include: establishing a relationship, setting goals,
      communication, acceptance, advocacy, flexibility, symptom relief, and recognising
      the identity of each person. There was agreement upon the nature of obstacles
      that prevented ideal care being achieved including obstacles created by families,
      other health professionals, administrative structures, and conflicts between the
      aims of care for a particular patient. Finally each clinician has a well
      developed set of personal views of the acceptable limits to practice, although
      these views vary widely. The clusters of ideas emerging in this study describe
      three objects of different ontologic status. The elements of ideal care are
      conceptual in nature, highlighting the aspirations for workers. The obstacles
      reflect the real world that palliative care professionals must negotiate each
      day, giving rise to a form of care that was good enough. The acceptable standards
      and their limits is the degree to which staff will or will not accept the
      compromises in care raised by the real world of practice, reflecting the ethical
      stance of the workers. The pursuit of ideal care may be motivated by a complex
      mix of aspirations, real-world practicalities and fulfilment for both patients
      and staff.

PMID- 17187543
TI  - The turning point: Clinical identification of dying and reorientation of care.
AB  - Palliative care is increasingly organized within the setting of formal health
      care systems but the demarcation has become unclear between, on the one hand,
      care directed at cure and rehabilitation and palliative care aimed at relief of
      suffering on the other. With the purpose to increase the understanding about the
      turning point reflecting identification of dying and reorientation of care, this
      study explores this phenomenon as determined from health care records of a
      representative sample (n = 229). A turning point was identified in 160 records.
      Presence of circulatory diseases, sporadic confinement to bed, and deterioration
      of condition had a significant impact upon the incidence of such turning point.
      The time interval between the turning point and actual death ranged between one
      and 210 days. Thirty percent of these turning points were documented within the
      last day of life, 33% during the last 2-7 days, 19.5% during the last 8-30 days,
      13% during the last 31-90 days, and 4.5% during the last 91-210 days of life. The
      time interval between the turning point and actual death was significantly longer
      among individuals with neoplasm(s) and significantly shorter among individuals
      suffering from musculoskeletal diseases. Perhaps this reflects a discrepancy
      between the ideals of palliative care, and a misinterpretation of the meaning of
      palliative care in everyday clinical practice. The findings underscore that
      improvement in timing of clinical identification of dying and reorientation of
      care will likely favour a shift from life-extending care to palliative care.

PMID- 17187544
TI  - Peaceful awareness in patients with advanced cancer.
AB  - BACKGROUND: Previous studies have shown that prognostic awareness may be harmful
      to mental health yet beneficial for end of life care planning. The effects of
      prognostic awareness coupled with a sense of inner peace are unknown. METHODS: In
      the multisite, longitudinal Coping with Cancer Study, 280 patients with advanced
      cancer were interviewed at baseline. Patients defining themselves as "terminally
      ill" and/or "at peace" most days were paired with others on sociodemographic,
      mental health and advance care planning. Primary caregivers of deceased patients
      were interviewed 6 months postloss and compared on their physical and mental
      health and their perceptions of patients' end-of-life care and death. RESULTS:
      Overall, 17.5% of patients reported being both peaceful and aware. Peacefully
      aware patients had lower rates of psychological distress and higher rates of
      advance care planning (e.g., completing do-not-resuscitate [DNR] orders, advance
      care planning discussions with physicians) than those who were not peacefully
      aware. Additionally, peacefully aware patients had the highest overall quality of
      death as reported by their caretakers in a postmortem evaluation. Surviving
      caregivers of peacefully aware patients were more physically and mentally healthy
      6 months postloss than caregivers of patients who were "aware" but not peaceful.
      CONCLUSIONS: Patients with advanced cancer who are peacefully aware have better
      mental health and quality of death outcomes, and their surviving caregivers have
      better bereavement outcomes. Peaceful awareness is associated with modifiable
      aspects of medical care (e.g., discussions about terminal treatment preferences).

PMID- 17187545
TI  - Factors associated with pressure ulcers in palliative home care.
AB  - BACKGROUND: Studies have identified factors associated with pressure ulcers in
      many health care settings including acute care, complex continuing care, long
      term care, and home care. OBJECTIVE: The purpose of this study was to identify
      factors associated with pressure ulcers among palliative home care clients.
      Identifying associations specific to each setting is important for ulcer
      prevention and has implications for clients overall well-being and quality of
      life. METHODS: The study included all palliative home care clients diagnosed with
      terminal cancer from one palliative home care agency in Ontario. Information on
      health was gathered using the interRAI instrument for palliative care. RESULTS:
      The study found male gender, the inability to lie flat because of shortness of
      breath, catheter, or ostomy care, and a reduced ability to perform activities of
      daily living to be associated with pressure ulcers. SIGNIFICANCE OF RESULTS: In
      some instances, treatment and prevention of pressure ulcers is the primary goal
      of care. However, pressure ulcers are also suggestive of deterioration and
      considered as a part of the disease trajectory. Sometimes the primary goal of
      care of treatment and prevention is displaced by a greater need for comfort.

PMID- 17187546
TI  - Existential loneliness in a palliative home care setting.
AB  - BACKGROUND: The diagnosis of an incurable disease implies an existential crisis.
      This study focused on the emotions, perceptions, and experiences of existential
      isolation in palliative patients with cancer and their families. MATERIALS AND
      METHODS: A total of 40 respondents (20 patients and 20 family members) were
      interviewed in depth. All were Swedes who defined themselves as nonreligious. The
      patients were enrolled in an advanced hospital-based home care team. The
      interviews were taped, transcribed, and analyzed with a qualitative, hermeneutic
      method. RESULTS: The data revealed experiences of existential loneliness with the
      impending death as a primary source. Experiences of being alone in "a world of
      one's own" were common. The changes in everyday life and the increasingly
      restricted social interaction because of the illness meant that the patient
      partly lost the protection against isolation that the spirit of community
      normally provides. Other situations that had a triggered the existential
      isolation were, for example, when a patient in need of support was left alone,
      when he or she was treated disrespectfully or in a way that made him or her feel
      invisible, or when people avoided contact because of uneasiness or fear. Changes
      in one's own body and mood gave rise to feelings of loneliness and unfamiliarity
      toward oneself. When a staff member touched the patient's body in a nonempathic
      way, this could induce feelings of being treated like an animal.

PMID- 17187547
TI  - Hospice attitudes among assisted living and nursing home administrators, and the
      long-term care hospice attitudes scale.
AB  - OBJECTIVES: To examine the attitudes of residential care/assisted living (RC/AL)
      and nursing home (NH) administrators toward hospice and to assess facility and
      administrator characteristics related to those attitudes. DESIGN: Two exploratory
      factor analyses of the Hospice Attitudes Questionnaire using principal factors
      with a promax (oblique) rotation were conducted. One was in a sample of 390 RC/AL
      and NH administrators from four states (Florida, Maryland, North Carolina, and
      New Jersey) and the other included NHs from this and a second sample (n = 244).
      Association between facility and administrator characteristics and administrator
      attitudes towards hospice were examined among the 146 RC/AL administrators.
      RESULTS: Exploratory factor analysis in the full sample resulted in the 12-item
      Long-Term Care Hospice Attitudes Scale (LTC-HAS) with four component subscales:
      (1) emotional and spiritual support (three items, alpha = 0.83); (2) quality of
      care (four items, alpha = 0.78); (3) rapidity of death (three items, alpha =
      0.66) and (4) end-of-life care coordination (two items, alpha = 0.73). The
      overall alpha for the 12-item scale was 0.81. When exploratory factor analysis
      was conducted on the NH data only, a three-item subscale related to financing and
      billing (alpha = 0.66) also emerged. Four facility and three administrator
      characteristics that were significantly related to hospice attitudes included
      state, facility type, facility age, affiliation with another level of care; and
      age, race, and nurse training. CONCLUSION: Findings from this paper provide
      insight about RC/AL facility and NH administrators' attitudes towards Hospice
      using scale data, an area with limited research. They indicate positive attitudes
      toward Hospice care coordination, and that Hospice should supplement, as opposed
      to replace, the care provided by facilities. Findings also suggest areas where
      targeted outreach and further study may be recommended.

PMID- 17187548
TI  - An Evaluation of the Advanced Illness Management (AIM) Program: Increasing
      hospice utilization in the San Francisco Bay area.
AB  - BACKGROUND: In the Medicare population, end-of-life care is fragmented and
      hospice is underutilized. Evidence suggests that hospice care is associated with
      increased patient/family satisfaction and reductions in overall health care
      costs. Advanced Illness Management (AIM) is a home-based program established to
      ease the transition between curative and comfort care for seriously ill patients
      who lack coordinated hospital, home health, and hospice care. OBJECTIVE: Measure
      the impact of the AIM program on the discharge disposition of participating home
      health patients. DESIGN: Retrospective cohort study. SETTING/SUBJECTS: A total of
      435 patients who received home health services through the Sutter Visiting Nurse
      Association and Hospice (SVNA&H) and who were discharged between 2003 and
      September 2005 were included in this study. Participants were selected based on a
      life expectancy of 6 months or less and additionally matched on prognosis of
      current episode of illness and symptom status. Intervention patients were
      compared to those receiving usual home health care at two SVNA&H branches.
      RESULTS: In the within-branch comparison, a 28% difference was observed in the
      number of hospice referrals between patients who received the AIM intervention
      and Usual Care I (47% AIM; 33% UCI, p = 0.003). When patients receiving the AIM
      intervention were compared to patients from another branch, Usual Care II, a 67%
      difference emerged (47% AIM; 16% UCII, p < 0.0001). Among African American
      patients, 60% and 73% more patients were referred to hospice when AIM patients
      were compared to Usual Care I and Usual Care II patients, respectively (p <
      0.01). These differences persisted after controlling for symptom status, patient
      demographics and home health length of stay. CONCLUSIONS: The AIM program was
      successful at increasing hospice utilization through a targeted intervention
      focused on palliative and end-of-life care, increased patient education and
      decision making, and a dynamic treatment approach. The finding of increased
      utilization by African Americans, a population traditionally reluctant to use
      hospice, was particularly noteworthy.

PMID- 17187550
TI  - Update in cancer pain syndromes.
AB  - Cancer pain assessment and management are integral to palliative medicine. This
      paper reviews recent publications in the period 1999-2004 in the broad categories
      of epidemiology, pain assessment, nonpharmacologic approaches to cancer pain
      (radiation therapy, anesthetic blocks, palliative surgery and chemotherapy,
      complementary and alternative medicine), and in nociceptive pain, neuropathic
      pain, visceral pain, and bone pain.

PMID- 17187551
TI  - Regional cancer pain syndromes.
AB  - Cancer pain often presents in a body region. This review summarizes articles from
      1999-2004 relevant to cancer pain syndromes in the head and neck, chest, back,
      abdomen, pelvis, and limbs. Although the evidence is limited, progress is being
      made in further development of the evidence base to support and guide current
      practice.

PMID- 17187553
TI  - Pain assessment in the cognitively impaired #126.

PMID- 17187552
TI  - Pain and ethnicity in the United States: A systematic review.
AB  - BACKGROUND: Evidence suggests that racial and ethnic disparities exist in access
      to effective pain treatment. PURPOSE: To review evidence of these disparities and
      provide recommendations for care and further research. DESIGN: Systematic review.
      METHODS: We conducted a MEDLINE search using the MeSH terms of ethnic groups,
      minority groups, pain, analgesia, and analgesics. We included studies describing
      current practice patterns, utilization of available treatments, treatment
      outcomes, and patient and provider knowledge, attitudes, and behaviors. RESULTS:
      Our search identified 35 journal articles describing the effect of patient race
      and ethnicity on pain assessment and management. Three studies on pain assessment
      revealed that minority patients are more likely to have their pain underestimated
      by providers and less likely to have pain scores documented in the medical record
      compared to whites. Eleven of 17 studies found that African Americans and
      Hispanics are less likely to receive opioid analgesics and more likely to have
      their pain untreated compared to white patients. Three studies revealed that
      minority patients are more likely to have negative pain management index (PMI)
      scores-undertreated pain-compared to whites. Patient-related, provider-related,
      and pharmacy-related barriers to effective pain management were identified.
      CONCLUSION: The majority of studies reveal racial and ethnic disparities in
      access to effective pain treatment akin to disparities found in other medical
      services. Quality improvement initiatives that improve treatment of pain for all
      patients according to established guidelines should decrease disparities by race
      or ethnicity. Educational interventions should aim to improve patient-provider
      communication regarding pain and its treatment and should provide support around
      substance abuse issues. Further research is needed to examine pain treatment
      outcomes and to determine whether health care system factors lead to these
      disparities.

PMID- 17187554
TI  - Pain management in nursing homes: Analgesic prescribing tips #89.

PMID- 17187557
TI  - A review of short bowel syndrome and palliation: a case report and medication
      guideline.
AB  - While patients with short bowel syndrome are not common in palliative care, they
      can present challenges for palliative care professionals. The case presented
      highlights a specific difficulty encountered. Many medications are poorly
      absorbed from a short bowel and alternative routes of administration need to be
      considered. A search was conducted to identify reviews, reports, and other
      articles from January 1960 to February 2004. MEDLINE, Cochrane Library, and
      CINAHL (Cumulative Index of Nursing and Allied Health Library) and MIMs
      (Medimedia Australia) databases were searched. A review of major textbooks was
      also conducted. Information on the site of absorption, time to peak plasma
      concentration, alternate routes, and pharmacokinetic information is summarized
      and presented in table form. This case report and review should assist
      practitioners with the palliative management of patients with short bowel
      syndrome.

PMID- 17187562
TI  - Constipation near the end of life.

PMID- 17187565
TI  - Public health awareness of emerging zoonotic viruses of bats: a European
      perspective.
AB  - Bats classified in the order Chiroptera are the most abundant and widely
      distributed non-human mammalian species in the world. Several bat species are
      reservoir hosts of zoonotic viruses and therefore can be a public health hazard.
      Lyssaviruses of different genotypes have emerged from bats in America (Genotype 1
      rabies virus; RABV), Europe (European bat lyssavirus; EBLV), and Australia
      (Australian bat lyssavirus; ABLV), whereas Nipah virus is the most important
      recent zoonosis of bat origin in Asia. Furthermore, some insectivorous bat
      species may be important reservoirs of SARS coronavirus, whereas Ebola virus has
      been detected in some megachiropteran fruit bats. Thus far, European bat
      lyssavirus (EBLV) is the only zoonotic virus that has been detected in bats in
      Europe. New zoonotic viruses may emerge from bat reservoirs and known ones may
      spread to a wider geographical range. To assess future threats posed by zoonotic
      viruses of bats, there is a need for accurate knowledge of the factors underlying
      disease emergence, for an effective surveillance programme, and for a rapid
      response system. In Europe, primary efforts should be focussed on the
      implementation of effective passive and active surveillance systems for EBLVs in
      the Serotine bat, Eptesicus serotinus, and Myotis species (i.e., M. daubentonii
      and M. dasycneme). Apart from that, detection methods for zoonotic viruses that
      may emerge from bats should be implemented. Analyses of data from surveillance
      studies can shed more light on the dynamics of bat viruses, (i.e., population
      persistence of viruses in bats). Subsequently, studies will have to be performed
      to assess the public health hazards of such viruses (i.e., infectivity and risk
      of infection to people). With the knowledge generated from this kind of research,
      a rapid response system can be set up to enhance public health awareness of
      emerging zoonotic viruses of bats.

PMID- 17187566
TI  - Infectious clones of Chikungunya virus (La Reunion isolate) for vector competence
      studies.
AB  - The recent outbreak of Chikungunya virus (CHIKV) on several islands in the Indian
      Ocean and in India has focused attention on this reemerging virus and highlighted
      the need for development of new tools to study vector-virus-host interactions. We
      have constructed and characterized, in cell culture, Aedes aegypti and Ae.
      albopictus mosquitoes, infectious cDNA clones of CHIKV using a recent isolate
      from La Reunion Island. Comparison of the growth kinetics and infection rates of
      the viral isolate CHIKV strain LR2006 OPY1 (CHIKV-LR) and a full-length
      infectious clone (CHIKV-LR ic) indicate that the infectious clone has retained
      the viral phenotypes of the original isolate. Infectious clones that express
      green fluorescent protein (GFP) were also produced and characterized in cell
      culture and in Aedes mosquitoes. The CHIKV-LR 5'GFP infected Ae. aegypti and Ae.
      albopictus mosquitoes at a similar rate to the original virus and to the full
      length infectious clone. The CHIKV-LR 3'GFP only infected Ae. albopictus
      mosquitoes at similar rates. The development of these authentic infectious clones
      will enable targeted studies of the molecular determinants of infection,
      pathogenesis and transmission competence by Ae. aegypti and Ae. albopictus
      mosquitoes.

PMID- 17187568
TI  - Indirect flight of an African bat to Israel: an example of the potential for
      zoonotic pathogens to move between continents.
AB  - The transmission of harmful pathogens during commercial air flights is an
      increasing health concern. A potential, yet relatively overlooked source of
      zoonotic infectious diseases involves collisions of birds and bats with aircraft
      and long distance transport of their carcasses. We report a case of aerial
      transportation of the remains of an African fruit bat over three continents,
      following a collision with an aircraft, and demonstrate the relative ease with
      which zoonotic pathogens, such as rabies virus or other viruses associated with
      bats, may cross national boundaries and continents even. Improper handling and
      disposal of animal remains by airport personnel, may lead to exposure of both
      humans and local fauna to exotic pathogens. This in turn may trigger an epidemic
      with potentially devastating results.

PMID- 17187567
TI  - Confined animal feeding operations as amplifiers of influenza.
AB  - Influenza pandemics occur when a novel influenza strain, often of animal origin,
      becomes transmissible between humans. Domestic animal species such as poultry or
      swine in confined animal feeding operations (CAFOs) could serve as local
      amplifiers for such a new strain of influenza. A mathematical model is used to
      examine the transmission dynamics of a new influenza virus among three
      sequentially linked populations: the CAFO species, the CAFO workers (the bridging
      population), and the rest of the local human population. Using parameters based
      on swine data, simulations showed that when CAFO workers comprised 15-45% of the
      community, human influenza cases increased by 42-86%. Successful vaccination of
      at least 50% of CAFO workers cancelled the amplification. A human influenza
      epidemic due to a new virus could be locally amplified by the presence of
      confined animal feeding operations in the community. Thus vaccination of CAFO
      workers would be an effective use of a pandemic vaccine.

PMID- 17187569
TI  - High prevalence of West Nile virus: a continuing risk in acquiring infection from
      a mosquito bite.
AB  - The prevalence of West Nile Virus (WNV) was evaluated by diplex real-time RT-PCR
      assay for the years 2001-2005 in Culex species of mosquitoes, several species of
      dead birds, and clinically suspected mammals collected in Kansas. The analysis
      was performed using a TaqMan-based diplex real-time RT-PCR assay targeted against
      two regions of the WNV genome, envelope glycoprotein gene and 3' untranslated
      region. The assay aided in the accurate detection of WNV in mosquitoes at high
      prevalence for the years 2002-2005. Similarly, high incidence of birds that
      tested positive for WNV was detected in 2002-2004. WNV positives in mammals by
      the diplex real time RT-PCR assay included horses, squirrels, mules, sheep and a
      mountain goat. Majority of the equine WNV positives were detected only in the
      year 2002. Sequence analysis of a segment of the envelope glycoprotein gene from
      31 randomly selected WNV positive samples revealed variations in six samples at
      one or two nucleotide positions. The identity of high levels of WNV positives in
      Kansas parallels the recent reports on the widespread distribution of the virus
      in the United States. The continued detection of WNV in the mosquitoes is of
      significant public health concern and calls for continued surveillance and public
      health activities.

PMID- 17187570
TI  - Experimental infection of common garter snakes (Thamnophis sirtalis) with West
      Nile virus.
AB  - The role of various reptilian species in the infectious cycle of several
      arboviruses is documented, but their role in that of West Nile virus (WNV) is
      uncertain. Common garter snakes (Thamnophis sirtalis) were infected
      subcutaneously with 10(5) plaque forming units (PFU) WNV-Isr 98, five of nine
      snakes became viremic, and five exhibited persistent low levels of neutralizing
      antibodies. Four of the parentally infected snakes died and high titers of virus
      were found in multiple organ samples. In contrast, orally infected garter snakes
      did not become viremic, but viral RNA was detected in cloacal swabs. Since oral
      infection of predator birds by WNV is known, their ingestion of infected snakes
      may also result in their becoming infected.

PMID- 17187571
TI  - A simple spatial model to explain the distribution of human tick-borne
      encephalitis cases in hungary.
AB  - Tick-borne encephalitis (TBE) is a common medical problem in Hungary and
      throughout much of Europe and Asia. This paper develops a geographic model that
      helps to predict the distribution of human tick-borne encephalitis cases in
      Hungary. The model is tested on a dataset of serologically confirmed TBE cases
      mapped by patients' residences. Case densities (incidence rates) are compared to
      predicted distributions of TBE derived from digital land-cover data. Maps are
      analyzed at the county level and on a smaller spatial scale. The analyses
      identified three major factors that shape the geographic distribution of human
      TBE cases in Hungary. The most important component is the distribution of forest
      habitat. TBE incidence correlates positively with the amount of forested habitat
      in each county. On a finer scale, the amount of forests within a 2500-meter
      radius of each town and village correlated significantly with TBE incidence rate.
      Based on these data, about 30% of the variation in TBE incidence is accounted for
      by the specific distribution of forest habitats in Hungary. Besides the
      distribution of forests, differences in human land-use practices among regions
      also affect the distribution of TBE cases. Additionally, because of the low
      transmission rate of the virus to humans, the perceived distribution of TBE cases
      is affected by random stochastic events. As a consequence of stochastic
      variation, meaningful patterns in the distribution of TBE cases can be only
      recognized when data are analyzed over broader temporal and spatial scales.

PMID- 17187572
TI  - Tick-borne encephalitis virus in Clethrionomys glareolus in the Czech Republic.
AB  - A total of 474 specimens from 157 rodents caught at the military training area of
      Boletice in the south of the Czech Republic from May to November 1999 were
      screened for TBEV by nested PCR. TBEV-specific RNA was amplified from lung,
      kidney, and spleen derived from one Clethrionomys glareolus in the first RT-PCR
      round. Sequence analysis revealed a 100% identity to the TBEV strain Neudoerfl.
      TBEV presence in the sample was confirmed by mouse brain passage of backup
      samples and cell culture. The results support the observation that hantaviruses
      and TBEV transmission can occur sympatrically in the same rodent population.

PMID- 17187573
TI  - Pathogens and host DNA in Ixodes ricinus nymphal ticks from a German forest.
AB  - Unfed nymphs of Ixodes ricinus were collected from vegetation in a forest on the
      outskirts of Berlin, Germany and were analyzed for host and pathogen DNA.
      Pathogens were detected in 47% of the ticks. Borrelia afzelii was the commonest
      pathogen detected, followed by Rickettsia helvetica. Other pathogens included B.
      valaisiana, B. garinii, B. burgdorferi sensu stricto, Anaplasma phagocytophilum,
      and a relapsing fever-like Borrelia. Most of the host DNA detected was of rodent
      origin and was associated with infection by B. afzelii, R. helvetica, and A.
      phagocytophilum. Bird DNA was associated with B. valaisiana and B. garinii, and
      ruminant DNA with A. phagocytophilum. B. afzelii was also found in two ticks that
      contained bird DNA.

PMID- 17187574
TI  - Dissociation between inhibition and killing by levofloxacin in human granulocytic
      anaplasmosis.
AB  - Human granulocytic anaplasmosis (HGA) is a potentially fatal tick-borne infection
      caused by Anaplasma phagocytophilum. Treatment options are limited for this
      entity, with doxycycline being the drug of choice. Certain fluoroquinolones such
      as levofloxacin are active against A. phagocytophilum in vitro. We report a
      hospitalized patient with HGA who improved coincident with a 13-day course of
      levofloxacin therapy, but clinically and microbiologically relapsed 15 days after
      completion of treatment. Relapse of infection after levofloxacin therapy was
      reproduced in a severe combined immune-deficient (SCID) mouse infection model.
      Quinolone therapy should not be considered curative of HGA.

PMID- 17187575
TI  - Diversity of Bartonella genotypes in Richardson's ground squirrel populations.
AB  - The diversity and dynamics of Bartonella genotypes found in wild Richardson's
      ground squirrels (RGS), Spermophilus richardsonii were monitored at multiple
      sites in Saskatchewan, Canada from 2002 to 2004. Based on sequence analysis of a
      portion of the Bartonella citrate synthase (gltA) gene, four different genotypes
      were detected in 233 isolates from 176 animals. The majority (87%) of sequences
      were identified as genotype H, with genotypes I, J, and K accounting for 8%, 4%,
      and 1% of sequences, respectively. Only one animal was concurrently infected with
      multiple Bartonella genotypes. Of 23 animals sampled four times or more, 26% were
      never infected with Bartonella. Of 32 RGS infected with Bartonella at first
      capture and then sampled again the following month, 50% were infected with the
      same Bartonella genotype, 41% were no longer infected, and 9% were infected with
      a different Bartonella genotype in the subsequent sample. The diversity of
      Bartonella genotypes varied among sites. At one site almost all RGS were infected
      with genotype H in September, and up to 60% of the same population was infected
      with genotype I the following spring. We compare our results with previous
      studies of Bartonella infections in rodents and discuss possible explanations for
      the observed differences.

PMID- 17187576
TI  - Sympatric Ixodes trianguliceps and Ixodes ricinus ticks feeding on field voles
      (Microtus agrestis): potential for increased risk of Anaplasma phagocytophilum in
      the United Kingdom?
AB  - The importance of wild rodents as reservoirs of zoonotic tick-borne pathogens is
      considered low in the United Kingdom because, in studies to date, those
      parasitized by exophilic Ixodes ricinus ticks carry almost exclusively larvae and
      thus have a minor role in transmission cycles. In a cross-sectional study, 11
      (6.7%) of 163 field voles (Microtus agrestis) captured at field sites in Northern
      England were PCR-positive for Anaplasma phagocytophilum. The voles were found to
      act as hosts for both larval and nymphal I. ricinus and all stages of the
      nidicolous tick I. trianguliceps, and eight individuals were infested with ticks
      of both species at the same time. Two of 158 larval and one of 13 nymphal I.
      ricinus, as well as one of 14 larval and one of 15 nymphal I. trianguliceps
      collected from the rodents were PCR-positive. These findings suggest that
      habitats where field voles are abundant in the United Kingdom may pose a risk of
      A. phagocytophilum infection because (i) field voles, the most abundant
      terrestrial mammal in the United Kingdom, may be a competent reservoir; (ii) the
      field voles are hosts for both nymphal and larval ixodid ticks so they could
      support endemic cycles of A. phagocytophilum; and (iii) they are hosts for
      nidicolous I. trianguliceps, which may alone maintain endemic cycles, and
      exophilic I. ricinus ticks, which could act as a bridge vector and transmit
      infections to humans and domesticated animals.

PMID- 17187577
TI  - Mammal diversity and infection prevalence in the maintenance of enzootic Borrelia
      burgdorferi along the western Coastal Plains of Maryland.
AB  - The primary vector of Borrelia burgdorferi in North America, Ixodes scapularis,
      feeds on various mammalian, avian, and reptilian hosts. Several small mammal
      hosts; Peromyscus leucopus, Tamias striatus, Microtus pennsylvanicus, and Blarina
      spp. can serve as reservoirs in an enzootic cycle of Lyme disease. The primary
      reservoir in the northeast United States is the white-footed mouse, P. leucopus.
      The infection prevalence of this reservoir as well as the roles of potential
      secondary reservoirs has not been established in southern Maryland, a region of
      low to moderate Borrelia infection in humans. Intensive trapping at 96 locations
      throughout the western Coastal Plains of Maryland was conducted and we found that
      31.6% of P. leucopus were infected with B. burgdorferi. Sequence and phylogenetic
      analysis revealed that only B. burgdorferi sensu stricto circulated in southern
      Maryland. Feral house mice and voles also were infected and may serve as
      secondary hosts. Peromyscus gender, age and month of capture were significantly
      associated with infection status. Larval I. scapularis were the dominant
      ectoparasite collected from captured rodents even though host seeking A.
      americanum and D. variabilis were collected in greater numbers across the
      sampling region. Our findings illustrate that the enzootic cycle of LD is
      maintained in the western Coastal Plains region of southern Maryland between I.
      scapularis and P. leucopus as the dominant reservoir.

PMID- 17187578
TI  - Serologic evidence for exposure to Rickettsia rickettsii in eastern Arizona and
      recent emergence of Rocky Mountain spotted fever in this region.
AB  - During 2002 through 2004, 15 patients with Rocky Mountain spotted fever (RMSF)
      were identified in a rural community in Arizona where the disease had not been
      previously reported. The outbreak was associated with Rickettsia rickettsii in an
      unexpected tick vector, the brown dog tick (Rhipicephalus sanguineus), which had
      not been previously associated with RMSF transmission in the United States. We
      investigated the extent of exposure to R. rickettsii in the local area through
      serologic evaluations of children and dogs in 2003-2004, and in canine sera from
      1996. Antibodies to R. rickettsii at titers > or = 32 were detected in 10% of
      children and 70% of dogs in the outbreak community and 16% of children and 57% of
      dogs in a neighboring community. In comparison, only 5% of canine samples from
      1996 had anti-R. rickettsii antibodies at titers > or = 32. These results suggest
      that exposures to RMSF have increased over the past 9 years, and that RMSF may
      now be endemic in this region.

PMID- 17187579
TI  - Interview with Willy Burgdorfer, Ph.D. Interview by Vicki Glaser.

PMID- 17187582
TI  - Actions of sumatriptan on myenteric neurones: relief from an old headache in the
      enteric nervous system?

PMID- 17187583
TI  - Chronic constipation: advances in management.
AB  - Only a relatively small percentage of clinically constipated patients seek
      medical attention and most can be managed satisfactorily with conservative
      measures. This review mainly addresses those patients who have refractory or
      difficult-to-manage functional constipation who are referred to gastrointestinal
      specialists. Areas of review include insights into pathophysiology, the utility
      of diagnostic testing and the author's opinions concerning available
      pharmacologic agents, the role of behavioural therapies and the indications for
      surgical interventions in this heterogeneous group of patients.

PMID- 17187581
TI  - Aggregation of prion protein with insertion mutations is proportional to the
      number of inserts.
AB  - Mutation in the prion gene, PRNP, accounts for approx. 10-15% of human prion
      diseases. However, little is known about the mechanisms by which a mutant prion
      protein (PrP) causes disease. We compared the biochemical properties of a wild
      type human prion protein, rPrP(C) (recombinant wild-type PrP), which has five
      octapeptide-repeats, with two recombinant human prion proteins with insertion
      mutations, one with three more octapeptide repeats, rPrP(8OR), and the other with
      five more octapeptide repeats, rPrP(10OR). We found that the insertion mutant
      proteins are more prone to aggregate, and the degree and kinetics of aggregation
      are proportional to the number of inserts. The octapeptide-repeat and alpha-helix
      1 regions are important in aggregate formation, because aggregation is inhibited
      with monoclonal antibodies that are specific for epitopes in these regions. We
      also showed that a small amount of mutant protein could enhance the formation of
      mixed aggregates that are composed of mutant protein and wild-type rPrP(C).
      Accordingly, rPrP(10OR) is also more efficient in promoting the aggregation of
      rPrP(C) than rPrP(8OR). These findings provide a biochemical explanation for the
      clinical observations that the severity of the disease in patients with insertion
      mutations is proportional to the number of inserts, and thus have implications
      for the pathogenesis of inherited human prion disease.

PMID- 17187584
TI  - A new method for evaluation of intestinal muscle contraction properties: studies
      in normal subjects and in patients with systemic sclerosis.
AB  - Systemic sclerosis is a connective tissue disease that involves the
      gastrointestinal (GI) tract. Seventy-five per cent of systemic sclerosis patients
      experience symptoms arising from oesophagus. The intestine has less frequently
      been subject for studies than the oesophagus. When the small intestine becomes
      involved, nausea, vomiting, bloating, diarrhoea and malabsorption may occur.
      Previous studies have shown decreased and abnormal intestinal motility,
      dilatation and a stiffer wall. The aim was to study muscle mechanics in systemic
      sclerosis patients using novel analysis of intestinal muscle contraction force
      velocity and power. A volume-controlled duodenal ramp-distension protocol was
      used in nine patients and eight healthy controls. The wall stretch ratio,
      tension, shortening velocity and muscle power were computed from pressure and
      cross-sectional area data recorded by an impedance planimetry system. The tension
      stretch ratio relation obtained in patients was shifted to the left, indicating a
      stiffer wall. The in vivo tension-shortening velocity relationship was quantified
      using Hill's equation. The maximum preload tension (tension at zero velocity) was
      lower in the patients than in the healthy controls (P < 0.001). The muscle power
      was lowest in the patients. An association was found between the duration of the
      disease and the maximum stretch ratio (P < 0.05). The study represents the first
      data with application of in vivo muscle force-velocity relations in patients with
      gastrointestinal diseases. Systemic sclerosis patients had increased stiffness
      and impaired muscle dynamics of the duodenum. Decreased muscle function and
      increased wall stiffness may explain the GI symptoms reported in this patient
      group.

PMID- 17187585
TI  - Nutrient-dependent enhancement of rectal sensitivity in irritable bowel syndrome
      (IBS).
AB  - Food-related gastrointestinal symptoms are common in irritable bowel syndrome
      (IBS), but the mechanisms behind this are unclear. Enhanced colorectal
      sensitivity after duodenal lipid administration in IBS patients has been
      demonstrated. However, the effects of a regular meal on colorectal sensitivity in
      these patients and the importance of the composition of the meal are not known.
      On two separate days, 10 IBS patients and 11 controls randomly received a liquid
      meal (800 kcal), containing 60% calories from fat (fatty meal) or carbohydrate
      (carbohydrate meal). Using a barostat rectal sensitivity was assessed during four
      separate distension sequences before, immediately after and 30 and 60 min after
      the meal. In the patients, the discomfort (P = 0.04) and the pain thresholds (P =
      0.007) were gradually reduced after the fatty meal, whereas only a tendency in
      the same direction was seen after the carbohydrate meal. In patients VAS ratings
      for pain increased after the fatty meal (P = 0.03), but not after carbohydrates.
      In the controls, sensory thresholds were not affected by the meals. In IBS, a
      liquid meal enhances rectal sensitivity, and this seems to be partly nutrient
      dependent as a fatty meal has more pronounced effects than a carbohydrate meal.
      This might be of relevance for their postprandial symptoms.

PMID- 17187586
TI  - Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in
      humans.
AB  - ATI-7505, an investigational 5-HT(4) receptor agonist, was designed to have
      similar activity as cisapride without the cardiac adverse effects, i.e. without
      QT prolongation. In addition, ATI-7505 is not metabolized by CYP450. The aim of
      the study was to assess the effect of ATI-7505 on gastrointestinal (GI) and
      colonic transit in healthy humans. A randomized, parallel-group, double-blind,
      placebo-controlled study evaluated effects of 9-day treatment with ATI-7505 (3,
      10 or 20 mg t.i.d.) on scintigraphic GI and colonic transit in healthy volunteers
      (12 per group). Primary endpoints were gastric-emptying (GE) T(1/2), colonic
      geometric centre (GC) at 24 h and ascending colon (AC) emptying T(1/2). Daily
      stool diaries were kept. Analysis of covariance assessed overall treatment group
      differences, followed by post hoc unadjusted pairwise comparisons. There were
      borderline overall treatment effects (decrease) on GE T(1/2) (P = 0.154); the 20
      mg t.i.d. of ATI-7505-accelerated GE vs placebo (P = 0.038). ATI-7505 increased
      colonic transit (GC24, P = 0.031) with fastest transit at 10 mg t.i.d. vs placebo
      (P = 0.065). ATI-7505 accelerated AC emptying T(1/2) (overall P = 0.075) with 10
      mg dose vs placebo (P = 0.042). There was looser stool (Bristol stool form scale,
      overall P = 0.056) with the 10 and 20 mg t.i.d. doses. No safety issues were
      identified. ATI-7505 accelerates overall colonic transit and tends to accelerate
      GE and AC emptying and loosen stool consistency.

PMID- 17187587
TI  - Sumatriptan is an agonist at 5-HT receptors on myenteric neurones in the guinea
      pig gastric antrum.
AB  - Sumatriptan, a 5-hydroxytryptamine(1D) (5-HT(1D))-receptor agonist used in the
      treatment in migraine, inhibits gastric motility via the enteric nervous system.
      As no studies have reported enteric neuronal 5-HT(1D) receptors, we used
      conventional intracellular recordings to characterize the actions of sumatriptan
      on 145 guinea-pig antral myenteric neurones. In 24 of 29 neurones with a 5-HT(1P)
      receptor-mediated depolarizing response to 5-HT, application of sumatriptan
      caused a dose-dependent depolarization, accompanied by increased membrane
      resistance and enhanced excitability. Depolarizing responses to sumatriptan
      occurred both in cholinergic and in nitrergic neurones. Sumatriptan did not mimic
      the 5-HT(3) receptor-mediated fast-depolarizing responses or 5-HT(1A) receptor
      mediated inhibitory responses to 5-HT. Sumatriptan had no effect on neurones not
      responding to 5-HT. The depolarizing response to sumatriptan was inhibited by
      renzapride, but not by 5-HT(1-7) receptor antagonists. We conclude that
      sumatriptan behaves as an agonist at the 5-HT(1P) receptor on myenteric neurones
      in the guinea-pig gastric antrum. The actions of sumatriptan on gastric motility
      seem to be attributable to a direct action on enteric neurones.

PMID- 17187588
TI  - Muscarinic acetylcholine receptor activation increases transcellular transport of
      macromolecules across mouse and human intestinal epithelium in vitro.
AB  - The intestinal epithelium acts as a barrier restricting uptake of luminal
      macromolecules such as dietary antigens and microbes. Here, we examined the role
      of cholinergic signalling in the regulation of permeability to macromolecules.
      Mouse jejunum was mounted in Ussing chambers and permeability was determined by
      measuring the flux of the antigen-sized protein, horseradish peroxidase (HRP),
      across the tissue. Baseline HRP permeability was significantly reduced by neural
      blockade with tetrodotoxin or cholinergic muscarinic antagonism with atropine,
      suggesting that ongoing release of endogenous acetylcholine from enteric nerves
      regulates barrier function. Exogenous addition of the muscarinic agonist
      bethanechol caused significant increases in both HRP flux and the area of HRP
      containing endosomes in enterocytes. Bethanechol-enhanced HRP flux was abrogated
      by the M3 receptor antagonist, 4-diphenylacetoxy-N-methylpiperidine methiodide (4
      DAMP), the phospholipase A(2) inhibitor quinacrine, and the cyclooxygenase
      inhibitor indomethacin. Complementary in vitro studies showed direct effects of
      bethanechol on T84 epithelial cells, where increased HRP uptake was associated
      with increased F-actin, and increased cytosolic phospholipase A(2) (cPLA(2))
      phosphorylation. Taken together, these results provide evidence for cholinergic
      regulation of transepithelial transport of macromolecules, mainly mediated by
      activation of M3 receptors with subsequent involvement of phospholipase A(2) and
      cyclooxygenase products.

PMID- 17187589
TI  - Colonic luminal proteases activate colonocyte proteinase-activated receptor-2 and
      regulate paracellular permeability in mice.
AB  - Luminal activation of protease-activated receptors-2 (PAR(2)) on colonocytes by
      trypsin or PAR(2)-activating peptide increases colonic paracellular permeability
      (CPP). The aim of this study was to evaluate the role of proteases from
      endogenous and bacterial origin in the modulation of CPP and colonocyte PAR(2)
      expression in mice. CPP was assessed with (51)Cr-EDTA after intracolonic
      administration of different protease inhibitors. After 12 days of oral antibiotic
      treatment, measurements of colonic luminal serine protease activity (CLSPA), CPP,
      mucosal mouse mast cell proteinase-1 (MMCP-1) content, immunochemistry of PAR(2)
      and assessment of effects of PAR(2) agonist (SLIGRL) and mast cell degranulator
      (C48/80) on CPP in Ussing chambers were performed. Immunochemistry was repeated
      after intracolonic trypsin administration. Colonic infusion of protease
      inhibitors significantly reduced CPP. In antibiotic-treated mice, CLSPA was
      reduced coupled with a decrease in PAR(2) expression, but with no change in CPP
      and MMCP-1 content. Trypsin administration restored PAR(2) expression. The
      increase in CPP induced by SLIGRL and C48/80 was reduced after antibiotic
      treatment. Protease activity of colonic content plays an important role in the
      regulation of mucosal barrier through activation of PAR(2).

PMID- 17187590
TI  - The relationship between the effects of short-chain fatty acids on intestinal
      motility in vitro and GPR43 receptor activation.
AB  - The G protein-coupled receptors, GPR41 and GPR43, are activated by short-chain
      fatty acids (SCFAs), with distinct rank order potencies. This study investigated
      the possibility that SCFAs modulate intestinal motility via these receptors.
      Luminal SCFA concentrations within the rat intestine were greatest in the caecum
      (c. 115 mmol L(-1)) and proximal colon. Using similar concentrations (0.1-100
      mmol L(-1)), SCFAs were found to inhibit electrically evoked, neuronally mediated
      contractions of rat distal colon, possibly via a prejunctional site of action;
      this activity was independent of the presence or absence of the mucosa. By
      contrast, SCFAs reduced the amplitude but also reduced the threshold and
      increased the frequency of peristaltic contractions in guinea-pig terminal ileum.
      In each model, the rank-order of activity was acetate (C2) approximately
      propionate (C3) approximately butyrate (C4) > pentanoate (C5) approximately
      formate (C1), consistent with activity at the GPR43 receptor. GPR43 mRNA was
      expressed throughout the rat gut, with highest levels in the colon. However, the
      ability of SCFAs to inhibit neuronally mediated contractions of the colon was
      similar in tissues from wild-type and GPR43 gene knockout mice, with identical
      rank-orders of potency. In conclusion, SCFAs can modulate intestinal motility,
      but these effects can be independent of the GPR43 receptor.

PMID- 17187591
TI  - Chronic abdominal wall pain (CAWP).

PMID- 17187593
TI  - Developing a social brain.
AB  - A new account of human postnatal functional brain development, interactive
      specialization (IS), is introduced and applied to one important domain of human
      development: the social brain. Behavioural, ERP and fMRI evidence from newborns,
      infants and children in face processing tasks is briefly reviewed, and is shown
      to be consistent with predictions from the IS account. CONCLUSION: It is
      suggested that this new view of functional brain development can also be applied
      to other domains of typical and atypical human development.

PMID- 17187594
TI  - Persistent neuro-inflammation in cerebral palsy: a therapeutic window of
      opportunity?

PMID- 17187596
TI  - Resuscitation and ventilation strategies for extremely preterm infants: a
      comparison study between two neonatal centers in Boston and Stockholm.
AB  - AIM: To evaluate if different resuscitation and ventilatory styles exist between
      two neonatal units, and if the less aggressive approach has a beneficiary effect
      on BPD outcome. METHOD: Inborn infants delivered at a gestational age <28 weeks
      were retrospectively studied (Boston = 70 and Stockholm = 102). Data were
      collected from birth to discharge or to 40 weeks. RESULTS: The study groups were
      similar with regard to gestational age, birth weight, gender and CRIB score,
      whereas SNAPPE-II score was greater in Stockholm and prenatal steroids were given
      less frequently in Boston. In Stockholm, continuous positive airway pressure
      (CPAP) was applied in the delivery room for 56% of the infants and the prevalence
      of infants not requiring intubation or mechanical ventilation (MV) during the
      first week of life was 22%. In Boston all infants were initially intubated.
      Subsequently, CPAP was used less often, and higher mean airway pressures (MAWPs)
      were applied during the first 4 weeks of life. Mortality and moderate/severe BPD
      at 36 weeks were similar; however, at 40 weeks oxygen supplementation was more
      frequent in Boston. Site was a predictor for moderate/severe BPD or death at 40
      weeks. CONCLUSION: Practice style differences exist and the less aggressive
      approach with more CPAP administration was successful. It did not decrease the
      risk for BPD at 36 weeks; however, at 40 weeks, fewer infants were on oxygen
      support, and a strong association was found between site, MAWP or MV with
      pulmonary morbidity indicating that CPAP could have a beneficiary role in
      outcome.

PMID- 17187597
TI  - Oxygenation and ventilation in spontaneously breathing very preterm infants with
      nasopharyngeal CPAP in the delivery room.
AB  - AIM: To provide data on ventilation, oxygenation and acid-base state from birth
      to 48 h in very preterm infants treated with lung recruitment manoeuvre and
      nasopharyngeal continuous positive airway pressure in the delivery room. METHODS:
      Subjects of this prospective observational cohort study were 48 of 61 infants
      enrolled in a randomised controlled trial to test two lung recruitment manoeuvres
      after birth. The infants had received an arterial line in the delivery room. The
      outcome measures were data on oxygenation, ventilation and acid-base state during
      spontaneous breathing. RESULTS: Data are presented as (n [%]; median [minimum
      maximum]). 22 of 48 (46%) infants (gestational age, 26.4 [25.0-28.9] weeks; birth
      weight 870 [540-1310] g) were never intubated during the study. The FiO(2) of
      these infants was low (0.4 [0.21-0.45] at 45 min and 0.21 [0.21-0.5] at 48 h).
      PCO(2) reached its maximum at 24 (11-44) min (8 [6.4-10.8] kPa) and decreased
      below 6.7 kPa (median) within 3 h. The incidence of intracranial
      haemorrhage/periventricular leukomalacia did not increase with hypercapnia
      (pCO(2) > 8 kPa). CONCLUSION: A transient period of hypercapnia after birth may
      occur in spontaneously breathing very preterm infants supported with
      nasopharyngeal continuous positive airway pressure in the delivery room. The
      incidence of cerebral damage was not increased in infants with hypercapnia.

PMID- 17187598
TI  - Eosinophil activation in preterm infants with lung disease.
AB  - AIM: We investigated the role of eosinophils in the pathogenesis of
      bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Fifteen preterm
      infants with BPD were compared to 13 preterms with respiratory distress syndrome
      (RDS) and to 16 healthy preterms. We assessed total eosinophil and neutrophil
      counts in venous blood samples and the levels of the eosinophilic activity
      markers eosinophilic cationic protein (ECP) and the cellular surface antigen
      (CD9). RESULTS: The eosinophil count was greater in BPD compared with RDS and
      healthy infants (1414 vs. 797 and 471 cells per microlitre, respectively, p =
      0.03). ECP levels were elevated (34 vs. 12.8 and 9.8 microg/L, respectively, p =
      0.002) and CD9 levels reduced (75 vs. 94 and 86 mean fluorescence intensity
      units, respectively, p = 0.01) in BPD compared with RDS and healthy infants,
      suggesting eosinophilic activation in BPD. These findings were not solely
      explained by differences between gestational age or birth weight of the different
      groups. ECP levels were positively correlated with the duration of oxygen
      supplementation in the BPD group. The eosinophil count fell promptly after
      steroid treatment was commenced in the BPD group. CONCLUSION: The findings
      suggest that BPD is linked to eosinophil activation, which might contribute to
      the pathogenesis.

PMID- 17187599
TI  - Energy substrate production in infants born small for gestational age.
AB  - AIM: To investigate energy substrate production and its hormonal regulation in
      infants born small for gestational age. METHODS: Eleven infants, aged 24.4 +/-
      5.3 hour, were studied following a fast of 4.0 +/- 0.6 hour. Gestational age was
      35.4 +/- 2.8 weeks and birth weight 1804 +/- 472 g (<-2 SD). Rates of glucose
      production and lipolysis were analyzed using [6,6-(2)H(2)]-glucose and [2-(13)C]
      glycerol. RESULTS: Plasma levels of glucose and glycerol were 4.1 +/- 1.1 mmol x
      L(-1) and 224 +/- 79 micromol x L(-1), respectively. Glucose appearance averaged
      30.3 +/- 8.2 and glucose production rate 21.1 +/- 6.1 micromol x kg(-1) x
      minutes(-1). Glycerol production rate was 5.6 +/- 1.6 micromol x kg(-1) x
      minutes(-1), correlating strongly to birth weight (r = 0.904, p < 0.001). Of the
      glycerol produced, 55 +/- 22% was converted to glucose, corresponding to 8 +/- 3%
      of the glucose production. CONCLUSIONS: Even though the infants could produce
      energy substrates, lipolysis was reduced and the glucose production was in the
      low end of the normal range compared with infants born appropriate for
      gestational age. The correlation between glycerol production and birth weight
      indicates that lipolysis depends on the amount of stored fat. Data on insulin and
      insulin-like growth factor binding protein 1 support the view that insulin
      sensitivity in these infants is reduced in the liver but increased peripherally.

PMID- 17187600
TI  - Geographic variations in outcome of very low birth weight infants in Italy.
AB  - AIM: A number of social and health aspects in Italy show remarkable geographic
      dishomogeneity. We investigated if this phenomenon involves the outcome of very
      low birth-weight infants (VLBWI). METHODS: This is a multi-centre nation-based
      survey among all Italian NICUs. The number of VLBWI admitted to each NICU in 2001
      by birth-weight classes of 250 g, their inborn/outborn status and survival at
      discharge were registered through ad hoc questionnaires. The data were analysed
      for the whole country and for three geographic areas (North, Centre and South).
      RESULTS: A total of 4679 VLBWI in 125 units were surveyed (0.88% of live births
      in Italy in 2001). The median number of infants admitted was 34 per NICU
      (interquartile range 16,52), without significant differences among the three
      geographic areas. The inborn rate was 80.7% (86.5% in the North, 83.7% in the
      Centre and 74.6% in the South). The mortality rate was 19.6% (15.6% in the North,
      19.3% in the Centre and 23.4% in the South). Adjusted relative risk of death
      between Southern and Northern regions was 1.48 (95% CI 1.30-1.68), and that
      between outborn and inborn infants was 1.20 (95% CI 1.04-1.37). CONCLUSIONS: The
      differences in mortality among geographic areas suggest a state of socio-sanitary
      deprivation in the Southern regions, as well as different models of organisation
      and quality of perinatal care.

PMID- 17187601
TI  - Agreement between Cochrane Neonatal Group reviews and clinical guidelines for
      newborns at a Copenhagen University Hospital - a cross-sectional study.
AB  - AIM: To assess the agreement between Cochrane Neonatal Group reviews and clinical
      guidelines of a University Neonatology Department, to evaluate the reasons for
      potential disagreements and to ascertain whether Cochrane reviews were considered
      for the guidelines development. METHODS: The recommendations in the reviews and
      guidelines were compared and classified as being in 'agreement', 'partial
      agreement' or 'disagreement'. The guideline authors were interviewed for reasons
      about disagreement and whether Cochrane reviews were considered during the
      guideline development. RESULTS: Agreement between reviews and guidelines was
      found for 133 interventions (77%), partial agreement for 31 interventions (18%)
      and disagreement for nine interventions (5%). Six interventions were recommended
      in the guidelines, but not in the reviews. Three interventions were recommended
      in the reviews, but not in the guidelines. Use of consensus statements, evidence
      on surrogate markers, observational studies, basic immunology and
      pathophysiological knowledge, expert opinion, economical constraints,
      reservations about the external validity and unawareness of reviews were reasons
      for disagreement. Cochrane reviews were rarely (22%) used during the guideline
      development. CONCLUSION: We found agreement between more than three quarters of
      Cochrane reviews and neonatal guidelines. However, few important disagreements
      occurred. Reviews were only used for guideline development in about a fifth of
      cases.

PMID- 17187602
TI  - Preoperative lung function in newborn infants with univentricular hearts compared
      with healthy controls.
AB  - AIM: To measure the difference in lung function between newborns with
      univentricular hearts and healthy controls and study associations between lung
      function and pulmonary blood flow and pulmonary vasculature markings. METHOD:
      Tidal flow-volume measurements and single occlusion tests were performed before
      surgery on 25 unsedated spontaneously breathing newborns with univentricular
      hearts recruited over a 3-year period. Seventy-five healthy control infants were
      measured. Pulmonary blood flow was graded according to the haemodynamic effect of
      the echocardiographically defined anatomy of the heart defect. Pulmonary
      vasculature was graded according to radiological markings. RESULTS: The infants
      with univentricular hearts had a lower mean tidal volume of 4.7 ml (CI 2.3, 7.2,
      p < 0.001) (n = 24) and a lower mean compliance of the respiratory system of 12.7
      ml/kPa (CI 4.6, 20.8, p = 0.004) (n = 14). Pulmonary blood flow grading was
      associated with respiratory rate (r = 0.53, p < 0.001), tidal volume (r =-0.48, p
      < 0.001), compliance (r =-0.55, p < 0.001) and resistance (r =-0.31, p = 0.043).
      Pulmonary vasculature grading was associated with compliance (r =-0.68, p =
      0.006), resistance (r =-0.69, p = 0.007) and the time constant (r =-0.62, p =
      0.042). CONCLUSION: Newborns with univentricular hearts have reduced tidal
      volumes and reduced compliance of the respiratory system. The lung function
      abnormalities are associated with the degree of pulmonary blood flow and
      pulmonary vasculature markings.

PMID- 17187603
TI  - Prenatal diagnosis of congenital heart defects - a population based study.
AB  - AIM: The aim of this study was to describe the efficiency of routine prenatal
      ultrasound screening for the detection of cardiac defects in a Swedish region and
      to study the effect of prenatal diagnosis on the survival and outcome of the
      child. METHODS: We identified all fetuses and infants with a diagnosed major
      cardiac defect born in 1999-2003 in a region of Sweden using a register of the
      regional paediatric cardiac clinic, various health-care registers and registers
      of prenatally detected malformations. The outcome of newborns with and without a
      prenatal diagnosis of a cardiac defect was compared. RESULTS: During the study
      period, 77,241 infants were born in the area. Among 145 major cardiac defects,
      21% were detected prenatally. For the two university departments the detection
      rate was 38%. Of the major cardiac defects diagnosed <23 gestational weeks, 30%
      were terminated. No significant difference in the outcome was found between
      children with and without a prenatal diagnosis of a major cardiac defect.
      CONCLUSIONS: It could not be shown that survival and outcome for children with
      major cardiac defects was better when the defect was known prenatally than if it
      was detected postnatally. The size of the study prohibits conclusions on moderate
      differences.

PMID- 17187604
TI  - Quality of life in children with hypoplastic left heart syndrome.
AB  - AIM: To measure quality of life in children with hypoplastic left heart syndrome
      and their families. METHODS: A questionnaire exploring socioeconomic status,
      structure and function of networks and psychological well-being was completed by
      the families of all 18 patients older than 2 years (age range 2.7-10.6). The
      results were compared with those of 180 healthy Swedish children matched for age
      and sex. RESULTS: There were no significant differences between the groups in any
      of the aspects of socioeconomic status. Study group parents had not more
      available time for their child (p < 0.05) and more separations/divorces (p <
      0.01). The patients had lower self-esteem (p < 0.05), more psychosomatic symptoms
      (p < 0.01) [corrected] and lower peer acceptance (p < 0.01) than control
      children. CONCLUSION: With regard to psychological well-being, quality of life
      was significantly lower in children with hypoplastic left heart syndrome than in
      healthy controls.

PMID- 17187605
TI  - Psychosocial problems in children with cystic fibrosis.
AB  - AIM: To compare the well-being of children (7-14 years) with cystic fibrosis (CF)
      (n = 43) with the well-being of healthy controls (n = 1121). METHODS: The self
      report questionnaire Beck Youth Inventories (BYI) was used to study depression,
      anxiety, anger, disruptive behaviour and self-concept in children with CF. A
      measure of social desirability was included as well as body mass index (BMI) and
      percentage of predicted forced expiratory volume in one second (FEV(1)) as
      measures of health status. RESULTS: The children with CF did not differ from the
      norm group concerning depression, disruptive behaviour and self-concept. Young
      children with CF (7-10 years) and boys with CF scored significantly higher on
      anxiety. Girls with CF scored significantly lower on anger than controls. BMI was
      not associated with any of the BYI subscales. In patients aged 11-14 years, there
      was a significant correlation between FEV(1) and self-concept as well as a
      significant inverse correlation between FEV(1) and anxiety. CONCLUSIONS: Younger
      children with CF and boys with CF were more anxious than the healthy controls,
      and girls with CF expressed less anger than their healthy peers. Effects sizes
      however were small. Low FEV(1) was associated with low self-concept and high
      anxiety in adolescent patients.

PMID- 17187606
TI  - The effect of nutritional support on weight gain of HIV-infected children with
      prolonged diarrhoea.
AB  - AIM: To examine the effect on growth and immunity of enhanced calorie and protein
      provision to HIV-infected children presenting with prolonged diarrhoea. METHODS:
      A total of 169 HIV-infected children aged 6-36 months with diarrhoea for 7 days
      or more were randomly assigned to either standard nutrition support for children
      with prolonged diarrhoea or an enhanced diet started during hospitalisation and
      continued after discharge. The change in weight between enrolment and 8, 14 and
      26 weeks and changes in plasma HIV-RNA and CD4 cell count at 8 and 26 weeks were
      estimated. RESULTS: Children receiving enhanced nutrition achieved significantly
      more weight gain (p < 0.001) between enrolment and 8 weeks than children on the
      standard diet (median increase in weight-for-age standard deviation score +1.02
      vs. +0.01). After 8 weeks median weight velocity was normal and similar in both
      groups. The change in median CD4 count was similar in both groups. The 26-week
      mortality rate was high in both groups (standard support: 22%, enhanced support:
      29%). CONCLUSIONS: Nutrition support of children with advanced HIV infection and
      prolonged diarrhoea resulted in significant and sustained weight gain, but did
      not improve CD4 counts or survival. These results support integrated nutrition
      interventions for HIV-infected children.

PMID- 17187608
TI  - Effect of hyperbilirubinemia on intestinal permeability in healthy term newborns.
AB  - We investigated the effect of serum bilirubin (SB) on intestinal permeability
      (IP) of healthy, term, birth weight appropriate for gestational age neonates
      before phototherapy. IP was measured by the dual probe (lactulose/mannitol) sugar
      absorption test (SAT) performed on the third day of life in 12 healthy jaundiced
      newborns (total bilirubin 249 +/- 39.75 micromol/L) and compared to that of 12
      non-jaundiced newborns (total bilirubin 83.79 + 37.62 micromol/L) matched for
      sex, gestational age, birth weight and Apgar score. Jaundiced newborns have a
      significantly higher La/Ma ratio than non-jaundiced (0.31 +/- 0.28 vs. 0.053 +/-
      0.043; p < 0.0004). A significant correlation was found between serum bilirubin
      level and La/Ma ratio (r = 0.56 p < 0.006). CONCLUSION: Our study demonstrates a
      direct effect of UCB on gut epithelial barrier of at-term newborns in whom UCB
      appears to be responsible for an alteration of IP that theoretically may lead to
      a passage of macromolecules through the intestinal epithelium increasing the risk
      of sensitization.

PMID- 17187607
TI  - Intestinal permeability in different feedings in infancy.
AB  - AIM: To determine the intestinal permeability (IP) as a marker of intestinal
      epithelial integrity in formula-fed infants compared with healthy breast-fed
      infants. METHODS: IP was measured in 57 healthy infants less than 4 months old. A
      dual sugar test with lactulose and mannitol was performed. Three urinary ratios
      were established: lactulose/mannitol (L/M), lactulose/creatinine (L/C) and
      mannitol/creatinine (M/C). Five groups were studied: breast-fed (n = 11),
      prebiotic supplemented formula (n 17), nucleotides supplemented formula (n = 9),
      LC-PUFA supplemented formula (n = 9) and LC-PUFA and nucleotides supplemented
      formula (n = 11). RESULTS: We have not found any difference in IP between breast
      fed and formula-fed infants nor when the different formulas are compared with
      each other. The indirect information of the paracellular pathway by the ratio L/C
      and the transcellular route by the ratio M/C reflects some difference when the
      ingredients added are fructooligosaccharides and galactooligosaccharides,
      expressing a higher degree of lactulose permeation with respect to mannitol. When
      LC-PUFA supplementation was evaluated a lesser ratio of L/C was found, expressing
      intestinal barrier related to a process of epithelial tight. CONCLUSIONS: The
      most important factor in the maintenance of the integrity of epithelial barrier
      function is probably the delivery of nutrients in the gastrointestinal tract. The
      role of the different ingredients added should be clarified.

PMID- 17187609
TI  - A new method for the treatment of recurrent abdominal pain of prolonged negative
      stress origin.
AB  - OBJECTIVE: To test the hypothesis that psychological treatment given in
      combination with somatic treatment can relieve recurrent abdominal pain (RAP) of
      psychosomatic origin in childhood. STUDY DESIGN: Stomach Pain Clinic Group A,
      comprising 25 children receiving a combination of psychological treatment and
      physiotherapy given by two different persons and Stomach Pain Clinic Group B,
      comprising 23 children receiving physiotherapy only, were constituted in a
      randomized manner. Stomach Pain Clinic Group C, including 35 children receiving
      an integrated combination of psychological treatment and somatic treatment given
      by the same person was also constituted, as well as a reference group. Treatment
      outcome was measured by calculating a pain score and tender points (TP) score at
      inclusion and after 1 year. RESULTS: The pain score after 1 year improved
      significantly in all four groups. Stomach Pain Clinic Groups A and B did not show
      any significant difference, but Stomach Pain Clinic C had a significantly better
      outcome than Stomach Pain Clinic Group B. Stomach Pain Clinic Groups A and C had
      a significant decrease in the TP score after 1 year. Pain scores and TP scores
      calculated for all Stomach Pain Clinic groups correlated significantly at follow
      up after 1 year. CONCLUSION: For children with psychosomatic RAP, a special
      method for integrated psychological and somatic treatment is probably effective.
      The results have to be confirmed in a randomized controlled study. These children
      have a special pattern of TPs related to their disorder, which diminishes with
      improvement in the disorder.

PMID- 17187610
TI  - Improvement of the eradication rate of Helicobacter pylori gastritis in children
      is by adjunction of omeprazole to a dual antibiotherapy.
AB  - AIM: The possible improvement of efficacy and tolerability of a 7-day dual
      antibiotherapy amoxicillin-clarithromycin (AC) on the eradication of Helicobacter
      pylori (H. pylori) gastritis in children by the adjunction of omeprazole (OAC)
      was studied. METHODS: Forty-six children presenting with H. pylori gastritis,
      assessed at inclusion by endoscopy, H. pylori urease test, histology and/or
      culture were randomised to a twice-daily regimen of AC or OAC. A (13)C-urease
      breath test was performed 4-6 weeks after the end of the treatment period to
      evaluate H. pylori eradication. RESULTS: A larger proportion of patients was H.
      pylori negative (69%) in the OAC regimen treatment 4-6 weeks after eradication
      treatment compared with those who received dual AC therapy (15%). A total of
      seven patients (three in the OAC and four in the AC group) reported adverse
      events (AEs). Only vomiting was reported in more than one patient (one in each
      treatment regimen) and only one AE was severe (urticaria: in the OAC group, but
      considered not related to treatment). CONCLUSION: A larger eradication rate of H.
      pylori was obtained in the triple OAC group than in the dual AC group. Both
      therapy regimens can be safely administered to children for 7 days.

PMID- 17187612
TI  - Quality of infant feeding counselling for HIV+ mothers in Brazil: challenges and
      achievements.
AB  - AIM: This project aimed to assess the information and counselling on infant
      feeding in HIV+ mothers. METHODS: A cross-sectional study, based on 118
      structured observations of mothers' visits to health professionals (5
      8/professional)-in 15 purposively selected HIV/Aids healthcare units in Sao
      Paulo. RESULTS: The general quality of communication and counselling skills was
      good: for example, professionals responded to all mothers' questions (98%); kept
      eye-to-eye contact (82%); encouraged the mother to talk (77.1%). However, the
      information provided to mothers aimed to help their choices concerning infant
      feeding was of very poor quality. No mother, for example, was informed about
      alternatives to formula feeding and the danger of mixed feeding. None was offered
      the option of using banked breast milk. Only around 20% of mothers were informed
      about the safe preparation of formula feeding. When counselled by a nutritionist
      (compared with a paediatrician) more mothers were informed about the correct way
      to prepare bottle-feeds. No mention was made of cup feeding. CONCLUSION: Although
      health workers have good communication skills, the information provided to HIV+
      mothers is insufficient. Recommending against breast-feeding and providing infant
      formula may not be enough to achieve safer infant-feeding practices.

PMID- 17187611
TI  - Recurrent gastroesophageal reflux in neurologically impaired patients after
      fundoplication.
AB  - AIM: To evaluate the outcome and analyse the main causes of complications and
      failures of antireflux surgery for gastroesophageal reflux disease (GERD) in
      neurologically impaired patients (NIP). METHODS: From 1985 to 1999 44 NIP (mean
      age 12 years) underwent surgery for GERD. Type of surgery, complications and
      recurrent reflux were analysed. RESULTS: Twenty-seven patients (61%) showed
      preoperatively severe failure to thrive. All patients showed pathologic results
      in 24-h pH monitoring. Surgical treatment consisted of ventral (n = 25, Thal) or
      dorsal (n = 4, Toupet) semifundoplication or a Nissen fundoplication (n = 15).
      Postoperatively, all patients showed an impressive growth, regress of symptoms
      and improvement of results of diagnostic investigations. Late complications and
      recurrence of reflux were significantly related to preoperative extreme dystrophy
      (p < 0.0025). In six patients (15%) severity of symptoms related to recurrent
      reflux required a reoperation 17.8 month postoperatively (range 8-35 month).
      Recurrent reflux was found in 40% after ventral semifundoplication and in 46%
      after Nissen fundoplication (8 and 47 months postoperatively, respectively).
      CONCLUSION: Symptoms improved impressively after fundoplication in mentally
      retarded children. The incidence of recurrent reflux is not related to the type
      of surgery, however, it occurs significantly earlier with ventral
      semifundoplication when compared with Nissen fundoplication. Both late
      complications as well as recurrent reflux are related significantly to
      preoperative dystrophy.

PMID- 17187613
TI  - Validating and updating a prediction rule for serious bacterial infection in
      patients with fever without source.
AB  - AIM: To externally validate and update a previously developed rule for predicting
      the presence of serious bacterial infections in children with fever without
      apparent source. METHODS: Patients, 1-36 mo, presenting with fever without
      source, were prospectively enrolled. Serious bacterial infection included
      bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection,
      bacterial gastroenteritis, osteomyelitis/ethmoiditis. The generalizability of the
      original rule was determined. Subsequently, the prediction rule was updated using
      all available data of the patients with fever without source (1996-1998 and 2000
      2001, n = 381) using multivariable logistic regression. RESULTS: the
      generalizability of the rule appeared insufficient in the new patients (n = 150).
      In the updated rule, independent predictors from history and examination were
      duration of fever, vomiting, ill clinical appearance, chest-wall retractions and
      poor peripheral circulation (ROC area (95%CI): 0.69 (0.63-0.75)). Additional
      independent predictors from laboratory were serum white blood cell count and C
      reactive protein, and in urinalysis > or = 70 white bloods (ROC area (95%CI):
      0.83 (0.78-0.88). CONCLUSIONS: A previously developed prediction rule for
      predicting the presence of serious bacterial infection in children with fever
      without apparent source was updated. Its clinical score can be used as a first
      screening tool. Additional laboratory testing may specify the individual risk
      estimate (range: 4-54%) further.

PMID- 17187614
TI  - MRSA in children from foreign countries adopted to Swedish families.
AB  - AIM: To determine if children adopted to Swedish families from countries with a
      high carrier rate of methicillin-resistant Staphylococcus aureus (MRSA) are
      infected or colonized with MRSA. METHODS: From January 2000 to May 2005, 23
      adopted children from 6 countries were examined for MRSA at the University
      hospital in Lund after their arrival in Sweden. RESULTS: Thirteen of the 23
      children (57%) were MRSA positive with a median age of the children at the time
      MRSA was detected of 6 (range 3-16) months. All MRSA positive children had a
      history of hospitalization in their native country before arriving in Sweden. The
      throat was the most frequent and persistent site where MRSA was seen while in
      sites such as the anterior nares and perineum, MRSA was found more
      intermittently. The MRSA-positive children were adopted into 13 Swedish families
      and in 3 families, 6 of 10 family members became MRSA positive. CONCLUSION:
      Children adopted from foreign countries to Swedish families and with a history of
      hospitalization in their native country were commonly colonized with MRSA. The
      throat was the most frequent site colonized and transmission of MRSA from adopted
      children to other family members occurred.

PMID- 17187615
TI  - The association between non-alcoholic fatty liver disease and insulin resistance
      in 20 obese children and adolescents.
AB  - AIM: To investigate whether there are correlations between non-alcoholic fatty
      liver disease (NAFLD) and insulin resistance in obese children. For the first
      time, we present clinical data of 20 obese children with NAFLD, including an oral
      glucose tolerance test. METHODS: Twenty obese children were diagnosed as having
      NAFLD by abdominal ultrasonography. Serum levels of alanine aminotransferase
      (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (gamma-GT)
      were reported. Insulin sensitivity was evaluated by oral glucose tolerance test,
      oral glucose insulin sensitivity (OGIS) and homeostasis is model assessment
      (HOMA) index. All parameters were compared to 20 obese age- and sex-matched
      patients without NAFLD. RESULTS: With 81% the prevalence of insulin resistance
      according to HOMA or OGIS criteria was high in the NAFLD-patients compared to the
      other group with 63%. Statistically significant differences between both groups
      were found for mean serum ALT levels, mean glucose levels after 30, 60 and 90
      minutes and mean insulin levels after 60 minutes of the glucose tolerance test.
      CONCLUSION: The high prevalence of insulin resistance we found in children with
      NAFLD confirms the suggestion that there may be an association between insulin
      resistance and NAFLD in obese children and indicates that markers of insulin
      sensitivity could be useful screening parameters for NAFLD.

PMID- 17187616
TI  - Obesity in 4-year-old children more prevalent in girls and in municipalities with
      a low socioeconomic level.
AB  - AIM: To provide updated prevalence data of BMI and obesity in 4-year-old Swedish
      children, also exploring socioeconomic differences. SUBJECTS: A total of 4407
      children born 1998-1999 (2231 boys and 2176 girls) in the county of Vasterbotten,
      Sweden. METHODS: Overweight and obesity was estimated using the International
      Obesity Task Force cutoff values (ISO BMI). Information about socioeconomic level
      of the municipalities was collected from a health survey of the adult population.
      RESULTS: Of the boys, 16.7% were classified as overweight and 3.1% of these as
      obese. Corresponding figures for girls were 22.1% and 6%. [corrected] The P50 and
      P95 values for BMI were 16.2 and 18.8 for boys and 16.1 and 19.3 for girls,
      respectively. P50 was at the same level as in previous Swedish studies, while P95
      was higher in this study. Obesity, in girls, was more prevalent in municipalities
      with a low socioeconomic level. CONCLUSION: Overweight and obesity in pre-school
      children in Sweden is more prevalent in girls than in boys, and the prevalence is
      as high as in school age children. A low socioeconomic level of living area seems
      to be related to a higher prevalence of obesity. Increased preventive efforts,
      both on the individual and the societal level, must be undertaken to reduce
      future health risks in obese children.

PMID- 17187617
TI  - Regulating physician-assisted dying for minors in the Netherlands: views of
      paediatricians and other physicians.
AB  - AIM: In 2002, the Dutch Euthanasia Act came into effect, which made euthanasia
      available to individuals from the age of 12 and above. The objective of our study
      was to gain insight into how Dutch paediatricians and other physicians treating
      children feel about the regulation of physician-assisted dying. METHODS: We
      interviewed 63 paediatricians, 125 general practitioners and 208 clinical
      specialists about their views on physician-assisted dying and the Euthanasia Act.
      RESULTS: Of the paediatricians, 44% agreed with the age limit of 12 years, and
      52% agreed with the requirement that parents be involved. Somewhat more than half
      thought the Act could contribute to the disclosure of end-of-life practices
      (52%), the quality of the review procedure (61%), careful decision making (54%)
      and the reporting rate (65%). These percentages were comparable for other
      physicians. A minority of the physicians in all groups indicated that, with this
      Act in place, they would be more willing to report such practices. The most
      optimistic in this respect were the paediatricians, of whom 39% expected such an
      effect. CONCLUSIONS: About half of Dutch paediatricians support the Euthanasia
      Act and expect it to achieve its aims, which is the same percentage as was found
      for other clinical specialists and general practitioners. However, most
      physicians do not foresee an increase in willingness to report cases of physician
      assisted dying.

PMID- 17187618
TI  - Enzyme replacement therapy with agalsidase alfa in children with Fabry disease.
AB  - AIM: To assess the effects of enzyme replacement therapy (ERT) in children with
      Fabry disease. METHODS: Safety and efficacy of ERT with agalsidase alfa, 0.2
      mg/kg infused over 40 minutes every 2 weeks for 23 weeks, were studied in a
      multicentre open-label trial in nine boys and four girls. Median age at the start
      of the study was 11.0 years (range 3.5-18 years). RESULTS: Fifty-four adverse
      events were reported in 11 patients. No serious adverse events related to ERT
      were reported. Twelve of the 54 adverse events were considered possibly or
      probably related to ERT. Infusion reactions (8 mild, 3 moderate) occurred in four
      boys, in seven infusions. One boy developed IgG antibodies, although he continued
      to make good clinical progress. At the end of the study, two of the four boys and
      the one girl on regular pain medication at baseline had stopped taking
      analgesics. Brief Pain Inventory (BPI) scores decreased in most patients by week
      12 and were sustained until the end of the study. This change was greater in the
      boys, who had higher (worse) BPI scores at baseline. Pain-related quality of life
      (QoL) scores also decreased during the study. Plasma globotriaosylceramide
      concentrations and urinary globotriaosylceramide:sphingomyelin ratios decreased
      after 12 and 23 weeks of therapy, particularly in the boys. Increases in sweat
      volume were recorded in three out of five of the boys and in one of two girls
      tested after 23 weeks of treatment. CONCLUSION: ERT with agalsidase alfa in
      children with Fabry disease is well tolerated and, in the short term, appears to
      decrease pain and to improve pain-related QoL.

PMID- 17187620
TI  - Identification of a novel compound heterozygote SCO2 mutation in cytochrome c
      oxidase deficient fatal infantile cardioencephalomyopathy.
AB  - Fatal infantile cardioencephalomyopathy (OMIM No. 604377) is a disorder of the
      mitochondrial respiratory chain and is characterised by neonatal progressive
      muscular hypotonia and cardiomyopathy because of severe Cytochrome c oxidase
      deficiency. Here we report a novel mutation in the Cytochrome c oxidase assembly
      gene SCO2 in an infant with fatal infantile cardioencephalomyopathy despite
      normal initial metabolic screening. CONCLUSION: In newborns with unexplained
      muscular hypotonia and cardiomyopathy genetic testing of mitochondrial
      respiratory chain disorders might be helpful to establish a final diagnosis and
      guide treatment decisions.

PMID- 17187619
TI  - Severe adverse reactions to Infliximab therapy are common in young children with
      inflammatory bowel disease.
AB  - Since 2000 we have introduced 141 Infliximab infusions to 23 children with severe
      inflammatory bowel disease. A total of seven severe adverse reactions occurred in
      26% (6 of 23) of the children. Four reactions were acute (anaphylaxis n = 2;
      allergic reaction n = 2) and 3/4 of these children were younger than 10 years of
      age. Two children developed an abscess and one child had septicaemia and brain
      lesions related to progressive multifocal leucoencephalopathy. CONCLUSION:
      adverse reactions to Infliximab infusions are common. Young children seem to be
      prone to severe allergic reactions although they are on azathioprine and
      conventional glucocorticoid therapy.

PMID- 17187621
TI  - Is there a connection between severe cerebral palsy and increased gluten
      sensitivity?
AB  - In nine children with severe cerebral palsy (CP), feeding difficulties and poor
      development of weight and height, laboratory markers for metabolic and enteral
      dysfunction were studied. CONCLUSION: Four of the nine patients with CP had
      increased levels of antigliadin antibodies AGA (IgA), a finding which calls for
      further studies concerning the possible connection between increased celiac
      markers and CP.

PMID- 17187622
TI  - Rapunzel syndrome: a diagnosis overlooked.
AB  - We report two children who presented with a painless abdominal mass masquerading
      as a splenic enlargement. The paucity of symptoms resulted in delayed diagnosis.
      At laparotomy the trichobezoars were found to have a tail extending into the
      small intestine. CONCLUSION: This condition eludes diagnosis unless sought for
      particularly in the paediatric age group. Hence we present our experience of two
      consecutive cases of paediatric Rapunzel syndrome, along with the relevant
      literature and in retrospect, how an early diagnosis could have been made.

PMID- 17187623
TI  - Usefulness of diffusion-weighted MRI in human herpesvirus-6 encephalitis.
AB  - We report a patient with human herpesvirus-6 (HHV-6) encephalitis diagnosed by
      diffusion-weighted magnetic resonance imaging (DW-MRI). A previously healthy 10
      month-old girl developed acute encephalopathy. HHV-6 DNA was detected in her
      cerebrospinal fluid during the acute phase of the disease by polymerase chain
      reaction. The patient demonstrated cortical diffusion abnormalities in affected
      brain parenchyma, partially as the initial or most sensitive sign of encephalitis
      that could be detected not by conventional MRI but by DW-MRI. Serial imaging
      showed that the diffusion abnormality DW-MRI returned to normal after 45 days.
      CONCLUSION: DW-MRI may be a valuable tool for early detection and diagnosis of
      HHV-6 encephalitis and is more sensitive than conventional MRI to detect a subtle
      edematous change in the brain.

PMID- 17187624
TI  - Uncommon cause of late neonatal death with refractory respiratory distress
      syndrome.

PMID- 17187625
TI  - "One sometimes finds what one is not looking for" (Sir Alexander Fleming): the
      most important medical discovery of the 20th century.

PMID- 17187626
TI  - Selective neonatal BCG vaccination - a re-audit.

PMID- 17187627
TI  - Cervical mycobacterial lymphadenitis in Swedish children during the post-BCG
      vaccination era.

PMID- 17187628
TI  - A case of epicanthus, telecanthus, high palate, transitional vertebra associated
      with vesicoureteral reflux.

PMID- 17187629
TI  - Olfactory function in children with cystic fibrosis.

PMID- 17187630
TI  - Evidence-based surgery: time for change.

PMID- 17187631
TI  - Nonlinear stiffness profiles of external fixators constructed with composite
      rods.
AB  - OBJECTIVE: To determine if composite connecting rods confer nonlinear stiffness
      characteristics on unilateral and bilateral external skeletal fixators (ESF) in
      cranial-caudal bending and axial loading. STUDY DESIGN: Mechanical testing
      performed on models. SAMPLE POPULATION: Six models of 6-pin ESF constructs
      composed of birch dowels, a commercial ESF system, and composite connecting rods.
      METHODS: Unilateral and bilateral ESF configurations were assembled using either
      specially designed composite titanium and silicone (composite group) or solid
      titanium (solid group) connecting rods. Mechanical testing was performed in axial
      loading and 4-point cranial-caudal bending. Stiffness was determined at a low and
      high-load range, and was considered increasing and nonlinear if the stiffness at
      high loads was greater than at low loads. RESULTS: The stiffness of the solid
      group was linear in all testing modes and configurations. Bilateral composite
      fixators had a nonlinear increasing stiffness in axial loading and cranial-caudal
      bending. Unilateral composite fixators had a nonlinear increasing stiffness in
      axial loading, but not cranial-caudal bending. Solid connecting rods conferred a
      higher stiffness in all testing modes and configurations. CONCLUSIONS: Composite
      connecting rods resulted in nonlinear increasing axial and bending stiffness in
      bilateral fixators, and in axial load in unilateral fixators. CLINICAL RELEVANCE:
      Conventional ESF can be constructed so that the stiffness increases as load
      increases. This provides the surgeon with additional options to control the local
      mechanical environment of a healing fracture, which may be used to enhance
      fracture healing.

PMID- 17187632
TI  - Effect of meniscal release on rate of subsequent meniscal tears and owner
      assessed outcome in dogs with cruciate disease treated with tibial plateau
      leveling osteotomy.
AB  - OBJECTIVE: To determine and compare rates of meniscal tears after tibial plateau
      leveling osteotomy (TPLO) among 3 groups of dogs based on treatment method:
      arthrotomy with meniscal release (openR), arthrotomy without meniscal release
      (openNR), arthroscopy without meniscal release (scopeNR), and compare long term
      owner-assessed outcomes for the same groups. STUDY DESIGN: Retrospective cohort
      study. SAMPLE POPULATION: Stifles (n=254) of dogs that had TPLO. METHODS: The
      three groups were compared for significant (P<.05) differences in rate of
      subsequent tears using a chi(2) test. Odds ratios for likelihood of subsequent
      meniscal tears were determined. Data for signalment, outcome, time to peak
      function, and time to subsequent tear were compared for significant differences
      using ANOVA, t-test, or rank sum test. RESULTS: Subsequent meniscal tears were
      diagnosed in 16 cases (6.3%). Of dogs with subsequent meniscal tears, 9 had
      openNR, 4 had openR, and 3 had scopeNR; the proportion of subsequent meniscal
      tears was significantly different (P=.035) among groups. Odds ratio indicated
      that subsequent meniscal tear was 3.8 times more likely to occur for openNR than
      openR or scopeNR. No significant differences among groups were noted for measures
      of outcome. CONCLUSIONS: Meniscal release did not reduce the rate of subsequent
      meniscal tears when compared with cases treated arthroscopically or when compared
      with all cases combined, but may be advantageous when meniscal pathology cannot
      be comprehensively assessed in the cranial cruciate deficient stifle. Meniscal
      release had no effects on owner-assessed outcome as determined in this study.
      CLINICAL RELEVANCE: The low rates of subsequent meniscal tears in conjunction
      with the relatively high and equivocal levels of owner-assessed outcome and time
      to peak function for all 3 treatment groups suggest that any of these surgical
      management strategies can be considered acceptable. We suggest that a meniscal
      release be performed when complete and thorough exploration of the joint and
      meniscus cannot be, or are not, performed.

PMID- 17187634
TI  - Magnetic resonance imaging of the canine shoulder: an anatomic study.
AB  - OBJECTIVES: To describe the normal anatomy of the soft tissue stabilizing
      components of the canine shoulder identified by magnetic resonance imaging (MRI)
      and to evaluate specific acquisition sequences and planes for observing
      structures of diagnostic interest. STUDY DESIGN: Descriptive study. ANIMAL:
      Canine cadavers (n=3). METHODS: T1-weighted, proton density fat saturation (PD),
      and T2(*)-weighted gradient echo (GE) MRI sequences were obtained in the
      sagittal, transverse, and dorsal planes of the left shoulder of 3 canine
      cadavers. After imaging, each shoulder was embedded and thin sectioned. The
      corresponding right shoulder was frozen and thick sectioned. The anatomic
      structures on the histologic and frozen thick sections were visually correlated
      with the MR images. RESULTS: The sagittal plane provided a longitudinal view of
      the bicep, infraspinatus, and supraspinatus tendons. The biceps, supraspinatus,
      infraspinatus, and subscapularis tendons, and the medial and lateral glenohumeral
      ligaments were identified in the transverse and dorsal planes. The dorsal plane
      allowed for the bicep tendon to be evaluated transversely as it passed over the
      humeral head. The GE sequence was more useful in identifying tendons and
      ligaments. The PD sequence was more helpful in identifying fluid accumulations in
      the joint and around tendons. CONCLUSIONS: The tendinous and ligamentous
      structures that stabilize the canine shoulder joint can be readily identified
      with MRI. CLINICAL RELEVANCE: MRI has the potential to be a useful tool in the
      diagnosis of canine soft tissue shoulder injuries.

PMID- 17187633
TI  - In vivo evaluation of intra-articular protection in a novel model of canine
      cranial cruciate ligament mid-substance elongation injury.
AB  - OBJECTIVES: To evaluate the effects of intra-articular protection (IAP) on the
      canine cranial cruciate ligament (CrCL) and stifle in a CrCL midsubstance
      elongation injury model. STUDY DESIGN: Experimental longitudinal cohort study.
      ANIMALS: Skeletally mature female mixed breed hounds (n=12; mean+/-SEM weight,
      25.6+/-0.7 kg). METHODS: After CrCL elongation in 1 stifle of each dog, IAP was
      applied in 6 joints. In vivo assessment included radiographs, cranial-caudal
      joint translation, gait analysis, and synovial fluid levels of 3B3(-)
      (proteoglycan epitope) and C2C (collagen II neoepitope) up to 12 weeks after
      surgery. Joint translation and rotation were quantified at necropsy. CrCL
      midsubstance length was determined before and after elongation and at necropsy.
      CrCLs were subjectively assessed with light microscopy. Comparisons were made
      between stifles containing elongated CrCLs with and without IAP and unoperated
      controls. RESULTS: Four weeks after surgery, ground reaction forces were
      significantly decreased in operated limbs. Absolute C2C levels were significantly
      elevated in operated stifles 4 weeks post-surgery. C2C and 3B3(-) levels
      normalized to total protein were significantly elevated in IAP+ stifles 8 weeks
      after surgery. Protected CrCLs appeared to have decreased granulation tissue and
      better collagen fiber alignment. CONCLUSIONS: IAP has negligible effects on the
      canine stifle based on the response variables evaluated in this 12-week study.
      Protection of elongated CrCLs may promote reduced, organized scar formation.
      CLINICAL RELEVANCE: These results support the healing capacity of the canine CrCL
      midsubstance following elongation injury and IAP application to potentially
      reduce cicatrix formation in elongated CrCLs.

PMID- 17187635
TI  - Combination tibial plateau leveling osteotomy and cranial closing wedge osteotomy
      of the tibia for the treatment of cranial cruciate ligament-deficient stifles
      with excessive tibial plateau angle.
AB  - OBJECTIVE: To describe a surgical technique, and outcome, for treatment of
      cranial cruciate ligament (CrCL) deficient stifle joints with excessive tibial
      plateau angle (TPA) by combined tibial plateau leveling osteotomy and cranial
      closing wedge osteotomy (TPLO/CCWO). STUDY DESIGN: Retrospective clinical study.
      ANIMALS: Fifteen client-owned dogs (18 stifle joints). METHODS: Medical records
      of dogs that had TPLO/CCWO were reviewed. Pre- and postoperative TPA, CCWO
      technique, method of fixation and complications were recorded. In-hospital re
      evaluation of limb function and length of time to radiographic healing was
      reviewed. Long-term outcome was assessed by owner telephone interview. RESULTS:
      Mean pre- and postoperative TPA was 42 degrees and 8 degrees, respectively. The
      Slocum biradial saw was used to create the CCWO in 4 stifle joints (mean
      postoperative TPA, 16 degrees) and a sagittal saw was used in 14 stifle joints
      (mean postoperative TPA, 5 degrees). Postoperative surgical complications were
      documented in 77.8% of cases; including patellar tendon thickening (61.1%), and
      implant loosening or breakage (27.8%), seroma formation (11.1%), and local
      irritation (11.1%). A second surgical procedure was performed in one-third of
      cases primarily to retrieve implants. Mean time to documented radiographic
      healing was 18 weeks. Final in-hospital re-evaluation of limb function (mean, 23
      weeks postoperatively) was recorded as no lameness in 73.3% and mild lameness in
      26.7%. All interviewed owners were satisfied with outcome and 90.9% reported
      marked improvement or a return to preinjury status. CONCLUSIONS: Long-term
      clinical outcome of TPLO/CCWO was very good in dogs with excessive TPA, with high
      owner satisfaction. Longer healing times and a higher complication rate were
      observed compared with TPLO alone. CLINICAL RELEVANCE: TPLO/CCWO of the tibia in
      stifle joints with excessive TPA allows for full correction of the TPA to 5
      degrees without eliminating buttress support of the tibial tuberosity.

PMID- 17187637
TI  - Effect of nephrotomy on renal function and morphology in normal cats.
AB  - OBJECTIVE: To assess effects over 12 weeks of bisection nephrotomy on renal
      function, size, and morphology in cats. STUDY DESIGN: Controlled, randomized,
      blinded experiment. SAMPLE POPULATION: Ten adult female cats. METHODS: Glomerular
      filtration rate (GFR), determined by quantitative renal scintigraphy using
      (99m)Technetium-diethylenetriamine-pentaacetic acid, urinalysis, urine culture,
      and ultrasonographic measurement of renal size were performed preoperatively.
      Left or right nephrotomy (5 cats/group) was performed. Total and individual
      kidney GFRs were determined at 2, 28, and 84 days, ultrasonographic measurements
      at 28 and 86 days, and ultrasound-guided biopsy at 86 days. RESULTS: No
      significant differences in mean GFR and kidney size of operated versus unoperated
      kidneys were observed. Individual GFR and renal size of all except 1 cat remained
      within normal limits. Two cats had evidence of transient ureteral obstruction in
      the immediate postoperative period. No significant, generalized histologic
      abnormalities were observed. CONCLUSIONS: Bisection nephrotomy in normal cats
      does not adversely affect renal function or morphology during the initial 12
      weeks. CLINICAL RELEVANCE: Bisection nephrotomy can be safely performed in normal
      feline kidneys without causing a significant deleterious effect on renal
      function. Studies in cats with pre-existing renal insufficiency are needed to
      ensure adverse effects would not occur in clinical cases where this surgical
      procedure is warranted.

PMID- 17187636
TI  - Comparison of biofragmentable anastomosis ring and sutured anastomoses for
      subtotal colectomy in cats with idiopathic megacolon.
AB  - OBJECTIVE: To report use of a biofragmentable anastomosis ring (BAR) device in
      cats with idiopathic megacolon (FIM) and compare outcome after subtotal colectomy
      with sutured colocolic anastomosis. STUDY DESIGN: Retrospective study. ANIMALS:
      Nineteen cats with megacolon. METHODS: Medical records (January 1990-January
      2004) of cats treated surgically for idiopathic megacolon with sutured (SUT) or
      BAR anastomosis were retrieved and reviewed. Operative, short- and long-term
      complications, and survival times were recorded and Kaplan-Meier survival
      analysis used to assess outcome. RESULTS: There were 11 SUT and 8 BAR cats. One
      BAR cat had anastomotic dehiscence 36 hours after surgery. Mild serosal tearing
      during BAR insertion in 6 cats was corrected by suture reinforcement. One SUT cat
      developed anastomotic stricture at 32 days. Short-term complication rates at 3
      and 7 days were 18% and 45% in the SUT group and 25% and 87.5% in the BAR group,
      respectively (P=.058). Two SUT cats had persistent loose stool consistency and
      were euthanatized 254 and 1661 days after surgery. One BAR cat had recurrence of
      constipation which was managed medically. Long-term complication rates were not
      significantly different between SUT and BAR (P=.61). The 1 and 4-year survival
      rates were 90% for SUT and 100% for BAR (P=.29). CONCLUSIONS: No difference was
      detected for short and long-term complication rates and survival times between
      SUT and BAR groups. CLINICAL RELEVANCE: The BAR device can be used for colocolic
      anastomosis in cats with idiopathic megacolon. Serosal tearing during BAR
      insertion was a common intraoperative complication. Regardless of anastomotic
      technique, survival outcome after colonic resection is excellent for cats with
      FIM.

PMID- 17187639
TI  - Morphologic and functional features of the canine cruciate ligaments.
AB  - OBJECTIVE: To review the gross, microscopic, and functional anatomy of the
      cranial cruciate ligament (CCL) in dogs. STUDY DESIGN: Literature review.
      METHODS: Reports of the anatomy and function of the cruciate ligaments in dogs
      were retrieved by search of the 1975-2005 PubMed database. RESULTS: The CCL has
      an important biomechanical function resisting cranial drawer, hyperextension, and
      internal rotation and acts to fine tune and guide the stifle through its rolling
      and sliding motion. It has a complex architecture, and distinct geographic
      regions within the ligament have different functional roles depending on the
      angle and loading conditions. Collagen type I is the main component of the
      extracellular matrix; the fibrils have a crimped structure. The cruciate
      ligaments are almost completely covered by synovium, protecting them from
      synovial fluid. Cruciate blood supply is mainly of soft tissue origin. The
      intraligamentous network is relatively limited whereas the core of the middle
      third of the CCL is even less well vascularized. Neurohistologic studies are very
      limited in the dog. Various mechanoreceptors and proprioceptive receptors have
      been identified within the substance of the cruciate ligaments. CONCLUSIONS: CCL
      structural characteristics play an important part in its complex behaviour with
      the crimped pattern of the collagen fibrils being an important determinant of its
      biomechanical properties. In contrast to reports of managing CCL rupture, there
      are few reports describing the microanatomy and neurovascular morphology of the
      cruciate ligaments. CLINICAL RELEVANCE: Cruciate disease is likely multi
      factorial. Improved understanding of CCL degradation leading to CCL rupture is
      critical to development of new diagnostic tests for cruciate disease in dogs.
      Appropriate intervention during the early stages of disease process might
      preserve CCL structural properties by preventing further collagen degradation.
      Accurate knowledge of functional and fiber bundle anatomy is imperative for
      reconstruction and restoration of normal stifle joint physiology. Reconstructive
      goals should alleviate existing instability and mimic normal kinematics.
      Knowledge of the exact function of the CCL in the neuromuscular control around
      the stifle joint could possibly explain osteoarthritis progression after CCL
      damage.

PMID- 17187638
TI  - Preoperative immunosuppressive therapy and surgery as a treatment for anal
      furunculosis.
AB  - OBJECTIVES: To evaluate the efficacy of combining preoperative immunosuppressive
      therapy with surgical excision for treatment of anal furunculosis (AF) in dogs.
      STUDY DESIGN: Retrospective study. ANIMALS: Dogs (n=25) with stages 1-4 AF.
      METHODS: Preoperative immunosuppressive therapy was either cyclosporine A (CyA)
      alone or in combination with ketoconazole (Group 1; n=18), or azathioprine
      combined with prednisolone (Group 2; n=7). Surgical excision of residual draining
      tracts, cryptectomy, and anal sacculectomy were performed. Only dogs with
      postoperative clinical follow-up exceeding 9 months were retained for the study.
      RESULTS: Both immunosuppressive protocols were effective in reducing progression
      of AF. Subsequent draining tracts excision, cryptectomy, and anal sacculectomy
      were bilateral (12 dogs) or unilateral (13 dogs of which 4 had bilateral anal
      sacculectomy). Postoperative recovery was uneventful, except for 2 dogs that had
      wound breakdown. Recurrence was not observed in any of the dogs that had
      bilateral surgical excision and or in 9 dogs that had unilateral excision.
      CONCLUSION: Preoperative immunosuppressive therapy, combined with bilateral
      surgical resection of affected tissue consistently, resulted in resolution of AF.
      Four dogs that had recurrence had unilateral excision despite initial bilateral
      involvement, suggesting that all diseased tissue should be excised. CLINICAL
      RELEVANCE: These preliminary results suggest that immunosuppressive therapy
      before surgical excision for AF yields minimizes recurrence in dogs.

PMID- 17187640
TI  - Coil occlusion of residual shunts after surgical closure of patent ductus
      arteriosus.
AB  - OBJECTIVE; To describe use of coil embolization to occlude residual flow through
      a patent ductus arteriosus (PDA) after incomplete surgical ligation. STUDY
      DESIGN: Clinical study. ANIMALS: Dogs (n=4) with continuous murmur after surgical
      ligation of PDA. METHODS: After PDA ligation, residual ductal flow through the
      PDA was visible on color-flow Doppler examination and left ventricular end
      diastolic diameter remained increased. Coil embolization by an arterial approach
      was performed to achieve complete occlusion of the PDA. RESULTS: Embolization
      coils were delivered without complications and hemodynamically successful
      occlusion was achieved. Doppler-visible flow resolved in 2 dogs within 3 months
      after embolization. Left ventricular end-diastolic diameter indexed to body
      weight decreased in all dogs. CONCLUSIONS: Transcatheter coil embolization
      appears to be a safe and minimally invasive procedure for complete occlusion of
      residual PDA flow after incomplete surgical ligation. CLINICAL RELEVANCE:
      Transcatheter coil embolization should be considered for correction of
      hemodynamically significant residual shunts in dogs that have incomplete PDA
      occlusion after open surgical ligation.

PMID- 17187641
TI  - Incidence and breed predilection for dystocia and risk factors for cesarean
      section in a Swedish population of insured dogs.
AB  - OBJECTIVES: To estimate the incidence and breed predilection for canine dystocia
      using data from insurance claims. The risk factors for cesarean section (CS) were
      assessed for bitches with dystocia. STUDY DESIGN: Retrospective, longitudinal
      study. SAMPLE POPULATION: Insurance claims records (1995-2002) from a Swedish
      animal insurance database (Agria), including approximately 200,000 bitches.
      METHODS: The overall incidence rate of dystocia in insured bitches was calculated
      by dividing the number of reimbursed dystocia claims with the number of dog years
      at risk. Subsequently, incidence rates were stratified by breed, region, and
      habitat. The proportion of bitches with a dystocia claim that had CS were
      calculated, and risk factors for CS were assessed using a logistic regression
      model. RESULTS: Between 1995 and 2002, 3894 (2%) of 195,931 Swedish bitches
      included in the study had a reimbursed insurance claim for dystocia. The overall
      incidence rate of dystocia was 5.7 cases/ 1000 dog years at risk. Some breeds
      like the Scottish terrier were at increased risk of dystocia. Among bitches with
      dystocia, 63.8% were treated by CS. CONCLUSION: Dystocia in the bitch is more
      common than reported earlier. The risk of developing dystocia varies by breed,
      and a high percentage (63.8%) of affected bitches undergo CS. Clinical Relevance-
      Breeders and veterinarians could use this information to better predict which
      bitches are likely to experience dystocia and/or CS.

PMID- 17187643
TI  - Methods whereby lone surgeons might tension nylon loops before crimping.

PMID- 17187644
TI  - Intraoperative use of ultrasonography during continuous dorsal laminectomy in 2
      dogs with caudal cervical vertebral instability and malformation ('Wobbler
      syndrome').

PMID- 17187646
TI  - Intraoperative use of ultrasonography during continuous dorsal laminectomy in 2
      dogs with caudal cervical vertebral instability and malformation ('Wobbler
      syndrome').

PMID- 17187649
TI  - [S3-Guidelines for the therapy of psoriasis vulgaris].

PMID- 17187650
TI  - The innate host defence against nematode parasites.
AB  - Nematode parasites cause significant infections in both humans and animals. They
      are complex, multicellular organisms that present unique challenges for the host,
      in particular with respect to the recognition of their unusual surface structures
      by the innate defence system. The innate immune system is now recognized to be a
      critical component in the development of an adaptive effector response as well as
      a driver of vaccine-induced immunity. This paper will give an overview of current
      research on the innate barriers and immune mechanisms, cells, and receptors
      involved in the innate host response to nematode parasites. It will also review
      the 'nematode-associated molecular patterns' that may be specifically recognized
      by the host, in addition to other signals, such as nervous stimulation and tissue
      damage, that may alert the innate system to parasite invasion.

PMID- 17187651
TI  - Expulsion of the gastrointestinal cestode, Hymenolepis diminuta by tolerant rats:
      evidence for mediation by a Th2 type immune enhanced goblet cell hyperplasia,
      increased mucin production and secretion.
AB  - The processes underlying expulsion of Hymenolepis diminuta in rats are not known.
      Expression levels of mRNAs of several cytokines revealed a Th2 response that
      differed between worm infection levels. IL-4 protein levels decreased while IL-13
      levels increased in a 50-worm infection by 30 dpi; the converse was seen with a
      five-worm infection. A negative correlation was found between IL-4 or IL-13 mRNA
      expression and worm biomass, between IL-13 protein levels and worm number or worm
      biomass, and between IL-4 protein levels and worm biomass in 50-worm infections.
      A negative correlation between IL-4 mRNA or protein expression and worm biomass
      was observed with five-worm infections. A strong correlation between Muc2 mRNA
      expression and decreased worm number or biomass in a 50-worm infection was
      observed. Muc2 protein, goblet cell numbers and mucin decreased in a 50-worm
      infection by 20 days post-infection. These changes were not seen with five-worm
      infections where worms are not expelled. The data show that rats infected with 50
      H. diminuta mount a Th2 response leading to high levels of IL-13, increased
      goblet cell numbers and increased mucin2 production and release. The mucus traps
      the worms, which are progressively expelled from the small intestine.

PMID- 17187652
TI  - Analysis of the immune response to Neospora caninum in a model of intragastric
      infection in mice.
AB  - To study experimental Neospora caninum infection initiated at the
      gastrointestinal tract, Toll-like Receptor 4- and functional IL-12Rbeta2 chain
      deficient C57BL/10 ScCr mice were challenged intragastrically with 5 x 10(6) N.
      caninum tachyzoites. All parasite-inoculated mice eventually died with
      disseminated infection. In contrast, immunocompetent BALB/c mice challenged with
      1 x 10(7) N. caninum tachyzoites by the intragastric (i.g.) or the
      intraperitoneal (i.p.) route remained alive for at least 6 months. Expansion of
      splenic B- and T-cells, the latter displaying both activated and regulatory
      phenotypes, and increased levels of IFN-gamma and IL-10 mRNA were detected in
      both groups of infected BALB/c mice compared with non-infected controls, whereas
      in the Peyer's patches only IFN-gamma mRNA levels were found to be increased.
      Parasite-specific IgG1, IgG2a and IgA antibody levels were elevated in the sera
      of all infected mice, whereas increased N. caninum-specific IgA levels were
      detected in intestinal lavage fluids of i.g. challenged mice only. These results
      show that N. caninum infection can be successfully established in mice by i.g.
      administration of tachyzoites. They also show that the immune response elicited
      in i.g. or i.p. infected BALB/c mice, although conferring some degree of
      protection, was not sufficient for complete parasite clearance.

PMID- 17187653
TI  - Elevated plasma urokinase receptor predicts low birth weight in maternal malaria.
AB  - The blood level of soluble urokinase receptor (suPAR) is increased and associated
      with a poor clinical or fatal outcome in children with acute malaria. This study
      hypothesized that the suPAR level would be associated with foetal outcome in
      maternal malaria. suPAR was measured by ELISA in maternal and cord plasma samples
      taken during delivery in 253 pregnant Kenyan women stratified according to
      placental histology: no malaria infection (non-infected), active or active
      chronic infection (actively infected) or past-chronic infection (past-infected).
      Maternal-suPAR was higher in actively infected women (median 3.93 (IQR 2.92-5.29)
      ng/mL) compared with non-infected (median 2.78 (IQR 1.86-3.87) ng/mL, P = 0.001)
      and past-infected (median 2.67 (IQR 1.94-3.7) ng/mL, P = 0.012) women. Cord-suPAR
      was comparable across the groups (median 2.98 (IQR 2.38-3.77) ng/mL). In actively
      infected women, maternal-suPAR and gestational age were the only independent
      predictors of birth weight in multivariate linear regression adjusted for
      maternal-suPAR, HIV-1 infection, age, BMI, haemoglobin, peripheral parasitaemia,
      parity and gestational age; 1 ng/mL higher maternal-suPAR predicted -56 g (95% CI
      -100 to -12, P = 0.016) reduced birth weight. Cord-suPAR could not predict birth
      weight after adjusting for gestational age. Future studies are warranted to
      investigate whether the maternal suPAR level is increased earlier in pregnancy in
      women with active placental malaria infection and whether early maternal suPAR
      measurements can predict birth weight. If so, measurements of maternal suPAR
      early in pregnancy might then potentially identify women with increased needs for
      antenatal care and intervention.

PMID- 17187654
TI  - Expression of the recombinant protein disulphide isomerase of Teladorsagia
      circumcincta.
AB  - The aim of this experiment was to find an antigen from Teladorsagia circumcincta
      to measure the level of IgA in ovine serum samples. Previous experiments used the
      titre of IgA to select sheep resistant to infection with T. circumcincta. By
      Western blotting 22 experimentally infected ewes recognized many proteins, but
      not all of them were recognized by all animals. Sheep were divided into two
      groups of animals: those that recognized a protein in Western blotting and those
      that did not. Among all proteins, three showed significant associations between
      protein recognition and the titre of IgA in the serum.

PMID- 17187655
TI  - Oxybutynin transdermal system improves the quality of life in adults with
      overactive bladder: a multicentre, community-based, randomized study.
AB  - OBJECTIVE: To assess health-related quality-of-life (HRQoL) and safety with the
      oxybutynin transdermal system (OXY-TDS) (Oxytrol), Watson Pharma, Corona, CA,
      USA) in the Multicentre Assessment of Transdermal Therapy in Overactive Bladder
      With Oxybutynin (MATRIX) study, as HRQoL measurements are increasingly important
      in evaluating pharmacotherapy for overactive bladder (OAB). PATIENTS AND METHODS:
      This randomized, open-label, community-based study enrolled 2878 participants
      aged >/=18 years who had been given a diagnosis of OAB. The 327 study sites were
      representative of various practice types. All participants were treated with OXY
      TDS 3.9 mg/day for </=6 months. HRQoL was assessed using the King's Health
      Questionnaire (KHQ); the primary endpoint was the change in KHQ scores from
      baseline to study end. RESULTS: Most enrolees (2052/2625; 78.2%) had moderate to
      severe OAB at baseline (Patient Perception of Bladder Condition score >/= 4 on a
      scale of 1-6), and most (1632/2859; 57.1%) had been given previous drug treatment
      for OAB. Of 2592 with evaluable baseline KHQ scores, 92.2% reported urgency and
      88.2% reported urge urinary incontinence. The most impaired domains at baseline
      were Incontinence Impact (69.3), Symptom Severity (55.9), and Sleep/Energy
      (54.2). There were clinically meaningful and statistically significant
      improvements in nine of 10 domains at the study end; the greatest improvements
      were in Incontinence Impact (-13.5), Symptom Severity (-12.4), and Role
      Limitations (-13.3). The treatment was well tolerated, with low incidences of
      drug-related anticholinergic adverse effects such as dry mouth (75; 2.6%),
      constipation (44; 1.5%), and dizziness (21; 0.7%). There were drug-related
      application-site reactions, including pruritus, erythema, dermatitis and
      irritation, in 14.0% of participants. CONCLUSIONS: OXY-TDS treatment was well
      tolerated in this diverse, community-based population, and resulted in clinically
      significant improvements in HRQoL, regardless of baseline characteristics.

PMID- 17187656
TI  - Characterization of Treponema denticola pyrF encoding orotidine-5'-monophosphate
      decarboxylase.
AB  - The Treponema denticola ATCC 35405 genome annotation contains most of the genes
      for de novo pyrimidine biosynthesis. To initiate characterization of pyrimidine
      synthesis in Treponema, we focused on TDE2110 (the putative pyrF, encoding
      orotidine-5'-monophosphate decarboxlyase). Unlike the parent strain, an isogenic
      pyrF mutant was resistant to 5-fluoroorotic acid. In complex medium, growth of
      the pyrF mutant was independent of added uracil, indicating activity of a uracil
      uptake/salvage pathway. Transcription of pyrF was greatly reduced in T. denticola
      grown in excess uracil, demonstrating that de novo pyrimidine synthesis is
      regulated and suggesting a feedback mechanism. Treponema denticola PyrF
      complemented uracil auxotrophy in an Escherichia coli pyrF mutant. This study
      provides biochemical confirmation of T. denticola genome predictions of de novo
      and salvage pyrimidine pathways and provides proof of concept that pyrF has
      potential as a selectable marker in T. denticola.

PMID- 17187657
TI  - A global response to sulfur starvation in Pseudomonas putida and its relationship
      to the expression of low-sulfur-content proteins.
AB  - Sulfur is essential for life on Earth, but its availability is limited in many
      environments. Here the sulfur-starvation response of the model soil bacterium
      Pseudomonas putida KT2440 is shown to be associated with an approximately
      fivefold reduction in the total soluble thiol content of the cell. A
      bioinformatic survey of the P. putida KT2440 genome identified 646 genes encoding
      proteins with a significantly lower than average sulfur content (low sulfur
      content proteins, LSPs), the expression of which may have a role in the global
      reduction of cellular thiol content during sulfur starvation. Analysis of the
      genetic organization of the LSP-encoding genes showed that 31% were potentially
      transcriptionally associated with at least one other gene encoding a protein
      defined as an LSP. In particular, 55 LSP genes were located in three large
      clusters, termed low-sulfur islands (LSIs) here. The predicted identities of the
      proteins encoded by the LSIs strongly suggest that the LSIs have a role in
      acquiring sulfur from organic sulfur sources during sulfur starvation. This
      hypothesis was supported by transcription fusion studies on a limited number of
      LSP promoters under low-sulfur conditions. In a wider survey of bacterial
      species, LSIs were found to be more prevalent in free-living, Gram-negative
      bacteria than in Gram-positive or obligately intracellular bacteria.

PMID- 17187658
TI  - India's 'gold mine' of ancestral bacilli and the looming TB-HIV pandemic.

PMID- 17187660
TI  - Health-seeking behaviors and self-care practices of Dominican women with
      lymphoedema of the leg: implications for lymphoedema management programs.
AB  - BACKGROUND: In the Dominican Republic, a Latin American country with filariasis
      endemic areas, more than 63,000 people have lymphatic filariasis and more than
      400,000 people are at risk of future infection. In this paper, we explore the
      health beliefs, health-seeking behaviors and self-care practices of women with
      lymphoedema in filariasis-endemic areas to better understand the needs of women
      when developing lymphoedema morbidity control programs. METHODS: Qualitative data
      were collected through semi-structured interviews of 28 women, 3 focus group
      discussions with 28 women, field notes and photographs. RESULTS: Women described
      exhaustive and expensive attempts at seeking a cure for their lymphoedema. Family
      members were influential in providing women with initial care seeking referrals
      to indigenous healers credited with influence over physical, mental, spiritual
      and supernatural properties of illness. When indigenous treatments proved to be
      ineffectual, the women sought care from trained healthcare providers. Most
      healthcare providers incorrectly diagnosed the edema, failed to adequately treat
      and meet the needs of women and were viewed as expensive. Most women resorted to
      self-prescribing injectable, oral, or topical antibiotics along with oral
      analgesics as a standard practice of self-care. CONCLUSION: Healthcare providers
      must understand a woman's cultural perspectives of illness, her natural networks
      of support and referral, her behavioural practices of care-seeking and self-care
      and the financial burden of seeking care. In the culture of the Dominican
      Republic family members and traditional healthcare providers are influential
      advisors on initial health-seeking behaviors and self-care practices. For this
      reason family-oriented interventions, support groups for women and their
      families, community education and training on simple, low cost lymphoedema
      management techniques for indigenous healers are viable ways to influence the
      early detection, diagnosis and treatment of women with lymphoedema. The extensive
      use of injectable, oral and topical antibiotics by indigenous healers and women
      without medical supervision suggests a need for health education messages related
      to the risks of such practices.

PMID- 17187659
TI  - Tissue microarray analysis reveals a tight correlation between protein expression
      pattern and progression of esophageal squamous cell carcinoma.
AB  - BACKGROUND: The development of esophageal squamous cell carcinoma (ESCC)
      progresses a multistage process, collectively known as precursor lesions, also
      called dysplasia (DYS) and carcinoma in situ (CIS), subsequent invasive lesions
      and final metastasis. In this study, we are interested in investigating the
      expression of a variety of functional classes of proteins in ESCC and its
      precursor lesions and characterizing the correlation of these proteins with ESCC
      malignant progression. METHODS: Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4,
      annexin I, laminin-5gamma2 and SPARC were analyzed using immunohistochemistry on
      tissue microarray containing 205 ESCC and 173 adjacent precursor lesions as well
      as corresponding normal mucosa. To confirm the immunohistochemical results, three
      proteins, fascin, CK14 and laminin-5gamma2, which were overexpressed in ESCC on
      tissue microarray, were detected in 12 ESCC cell lines by Western blot assay.
      RESULTS: In ESCC and its precursor lesions, FADD, CDC25B, fascin, CK14, laminin
      5gamma2 and SPARC were overexpressed, while Fas, caspase 8, CK4 and annexin I
      were underexpressed. The abnormalities of these proteins could be classified into
      different groups in relation to the stages of ESCC development. They were "early"
      corresponding to mild and moderate DYS with overexpression of fascin, FADD and
      CDC25B and underexpression of Fas, caspase 8, CK4 and annexin I, "intermediate"
      to severe DYS and CIS with overexpression of FADD and CK14, and "late" to
      invasive lesions (ESCC) and to advanced pTNM stage ESCC lesions with
      overexpression of CK14, laminin-5gamma2 and SPARC. CONCLUSION: Analyzing the
      protein expression patterns of Fas, FADD, caspase 8, CDC25B, fascin, CK14, CK4,
      annexin I, laminin-5gamma2 and SPARC would be valuable to develop rational
      strategies for early detection of lesions at risk in advance as well as for
      prevention and treatment of ESCC.

PMID- 17187662
TI  - The role of sexually transmitted infections in male circumcision effectiveness
      against HIV--insights from clinical trial simulation.
AB  - BACKGROUND: A landmark randomised trial of male circumcision (MC) in Orange Farm,
      South Africa recently showed a large and significant reduction in risk of HIV
      infection, reporting MC effectiveness of 61% (95% CI: 34%-77%). Additionally, two
      further randomised trials of MC in Kisumu, Kenya and Rakai, Uganda were recently
      stopped early to report 53% and 48% effectiveness, respectively. Since MC may
      protect against both HIV and certain sexually transmitted infections (STI), which
      are themselves cofactors of HIV infection, an important question is the extent to
      which this estimated effectiveness against HIV is mediated by the protective
      effect of circumcision against STI. The answer lies in the trial data if the
      appropriate statistical analyses can be identified to estimate the separate
      efficacies against HIV and STI, which combine to determine overall effectiveness.
      OBJECTIVES AND METHODS: Focusing on the MC trial in Kisumu, we used a stochastic
      prevention trial simulator (1) to determine whether statistical analyses can
      validly estimate efficacy, (2) to determine whether MC efficacy against STI alone
      can produce large effectiveness against HIV and (3) to estimate the fraction of
      all HIV infections prevented that are attributable to efficacy against STI when
      both efficacies combine. RESULTS: Valid estimation of separate efficacies against
      HIV and STI as well as MC effectiveness is feasible with available STI and HIV
      trial data, under Kisumu trial conditions. Under our parameter assumptions, high
      overall effectiveness of MC against HIV was observed only with a high MC efficacy
      against HIV and was not possible on the basis of MC efficacy against STI alone.
      The fraction of all HIV infections prevented which were attributable to MC
      efficacy against STI was small, except when efficacy of MC specifically against
      HIV was very low. In the three MC trials which reported between 48% and 61%
      effectiveness (combining STI and HIV efficacies), the fraction of HIV infections
      prevented in circumcised males which were attributable to STI was unlikely to be
      more than 10% to 20%. CONCLUSION: Estimation of efficacy, attributable fraction
      and effectiveness leads to improved understanding of trial results, gives trial
      results greater external validity and is essential to determine the broader
      public health impact of circumcision to men and women.

PMID- 17187661
TI  - Differential gene expression of bone anabolic factors and trabecular bone
      architectural changes in the proximal femoral shaft of primary hip osteoarthritis
      patients.
AB  - Previous studies have shown a generalised increase in bone mass in patients with
      osteoarthritis (OA). Using molecular histomorphometry, this study examined the in
      vivo expression of mRNA encoding bone anabolic factors and collagen type I genes
      (COL1A1, COL1A2) in human OA and non-OA bone. Bone samples were obtained from the
      intertrochanteric (IT) region of the proximal femur, a skeletal site distal to
      the active site of disease, from individuals with hip OA at joint replacement
      surgery and from autopsy controls. Semi-quantitative reverse transcription
      polymerase chain reaction analysis revealed elevated mRNA expression levels of
      alkaline phosphatase (p < 0.002), osteocalcin (OCN) (p < 0.0001), osteopontin (p
      < 0.05), COL1A1 (p < 0.0001), and COL1A2 (p < 0.002) in OA bone compared to
      control, suggesting possible increases in osteoblastic biosynthetic activity
      and/or bone turnover at the IT region in OA. Interestingly, the ratio of
      COL1A1/COL1A2 mRNA was almost twofold greater in OA bone compared to control (p <
      0.001), suggesting the potential presence of collagen type I homotrimer at the
      distal site. Insulin-like growth factor (IGF)-I, IGF-II, and transforming growth
      factor-beta1 mRNA levels were similar between OA and control bone. Bone
      histomorphometric analysis indicated that OA IT bone had increased surface
      density of bone (p < 0.0003), increased trabecular number (Tb.N) (p < 0.0003),
      and decreased trabecular separation (Tb.Sp) (p < 0.0001) compared to control
      bone. When the molecular and histomorphometric data were plotted, positive
      associations were observed in the controls for OCN/glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) versus bone tissue volume (r = 0.82, p < 0.0007) and
      OCN/GAPDH versus Tb.N (r = 0.56, p < 0.05) and a negative association was
      observed for OCN/GAPDH versus Tb.Sp (r = -0.64, p < 0.02). These relationships
      were not evident in trabecular bone from patients with OA, suggesting that bone
      regulatory processes leading to particular trabecular structures may be altered
      in this disease. The finding of differential gene expression, as well as
      architectural changes and differences in molecular histomorphometric associations
      between OA and controls, at a skeletal site distal to the active site of joint
      degeneration supports the concept of generalised involvement of bone in the
      pathogenesis of OA.

PMID- 17187663
TI  - Multiplexed expression and screening for recombinant protein production in
      mammalian cells.
AB  - BACKGROUND: A variety of approaches to understanding protein structure and
      function require production of recombinant protein. Mammalian based expression
      systems have advantages over bacterial systems for certain classes of protein but
      can be slower and more laborious. Thus the availability of a simple system for
      production and rapid screening of constructs or conditions for mammalian
      expression would be of great benefit. To this end we have coupled an efficient
      recombinant protein production system based on transient transfection in HEK-293
      EBNA1 (HEK-293E) suspension cells with a dot blot method allowing pre-screening
      of proteins expressed in cells in a high throughput manner. RESULTS: A nested PCR
      approach was used to clone 21 extracellular domains of mouse receptors as CD4
      fusions within a mammalian GATEWAY expression vector system. Following transient
      transfection, HEK-293E cells grown in 2 ml cultures in 24-deep well blocks showed
      similar growth kinetics, viability and recombinant protein expression profiles,
      to those grown in 50 ml shake flask cultures as judged by western blotting.
      Following optimisation, fluorescent dot blot analysis of transfection
      supernatants was shown to be a rapid method for analysing protein expression
      yielding similar results as western blot analysis. Addition of urea enhanced the
      binding of glycoproteins to a nitrocellulose membrane. A good correlation was
      observed between the results of a plate based small scale transient transfection
      dot blot pre-screen and successful purification of proteins expressed at the 50
      ml scale. CONCLUSION: The combination of small scale multi-well plate culture and
      dot blotting described here will allow the multiplex analysis of different
      mammalian expression experiments enabling a faster identification of high yield
      expression constructs or conditions prior to large scale protein production. The
      methods for parallel GATEWAY cloning and expression of multiple constructs in
      cell culture will also be useful for applications such as the generation of
      receptor protein microarrays.

PMID- 17187665
TI  - A common genetic factor for Parkinson disease in ethnic Chinese population in
      Taiwan.
AB  - BACKGROUND: Parkinson's disease (PD) is the most common neurodegenerative
      movement disorder, characterized clinically by resting tremor, bradykinesia,
      postural instability and rigidity. The prevalence of PD is approximately 2% of
      the population over 65 years of age and 1.7 million PD patients (age > or = 55
      years) live in China. Recently, a common LRRK2 variant Gly2385Arg was reported in
      ethnic Chinese PD population in Taiwan. We analyzed the frequency of this variant
      in our independent PD case-control population of Han Chinese from Taiwan.
      METHODS: 305 patients and 176 genetically unrelated healthy controls were
      examined by neurologists and the diagnosis of PD was based on the published
      criteria. The region of interest was amplified with standard polymerase chain
      reaction (PCR). PCR fragments then were directly sequenced in both forward and
      reverse directions. Differences in genotype frequencies between groups were
      assessed by the X2 test, while X2 analysis was used to test for the Hardy
      Weinberg equilibrium. RESULTS: Of the 305 patients screened we identified 27 (9%)
      with heterozygous G2385R variant. This mutation was only found in 1 (0.5%) in our
      healthy control samples (odds ratio = 16.99, 95% CI: 2.29 to 126.21, p = 0.0002).
      Sequencing of the entire open reading frame of LRRK2 in G2385R carriers revealed
      no other variants. CONCLUSION: These data suggest that the G2385R variant
      contributes significantly to the etiology of PD in ethnic Han Chinese
      individuals. With consideration of the enormous and expanding aging Chinese
      population in mainland China and in Taiwan, this variant is probably the most
      common known genetic factor for PD worldwide.

PMID- 17187664
TI  - Identification of potential CepR regulated genes using a cep box motif-based
      search of the Burkholderia cenocepacia genome.
AB  - BACKGROUND: The Burkholderia cenocepacia CepIR quorum sensing system has been
      shown to positively and negatively regulate genes involved in siderophore
      production, protease expression, motility, biofilm formation and virulence. In
      this study, two approaches were used to identify genes regulated by the CepIR
      quorum sensing system. Transposon mutagenesis was used to create lacZ promoter
      fusions in a cepI mutant that were screened for differential expression in the
      presence of N-acylhomoserine lactones. A bioinformatics approach was used to
      screen the B. cenocepacia J2315 genome for CepR binding site motifs. RESULTS:
      Four positively regulated and two negatively regulated genes were identified by
      transposon mutagenesis including genes potentially involved in iron transport and
      virulence. The promoter regions of selected CepR regulated genes and site
      directed mutagenesis of the cepI promoter were used to predict a consensus cep
      box sequence for CepR binding. The first-generation consensus sequence for the
      cep box was used to identify putative cep boxes in the genome sequence. Eight
      potential CepR regulated genes were chosen and the expression of their promoters
      analyzed. Six of the eight were shown to be regulated by CepR. A second
      generation motif was created from the promoters of these six genes in combination
      with the promoters of cepI, zmpA, and two of the CepR regulated genes identified
      by transposon mutagenesis. A search of the B. cenocepacia J2315 genome with the
      new motif identified 55 cep boxes in 65 promoter regions that may be regulated by
      CepR. CONCLUSION: Using transposon mutagenesis and bioinformatics expression of
      twelve new genes have been determined to be regulated by the CepIR quorum sensing
      system. A cep box consensus sequence has been developed based on the predicted
      cep boxes of ten CepR regulated genes. This consensus cep box has led to the
      identification of over 50 new genes potentially regulated by the CepIR quorum
      sensing system.

PMID- 17187667
TI  - High magnetic field induced changes of gene expression in arabidopsis.
AB  - BACKGROUND: High magnetic fields are becoming increasingly prevalent components
      of non-invasive, biomedical imaging tools (such as MRI), thus, an understanding
      of the molecular impacts associated with these field strengths in biological
      systems is of central importance. The biological impact of magnetic field
      strengths up to 30 Tesla were investigated in this study through the use of
      transgenic Arabidopsis plants engineered with a stress response gene consisting
      of the alcohol dehydrogenase (Adh) gene promoter driving the beta-glucuronidase
      (GUS) gene reporter. METHODS: Magnetic field induced Adh/GUS activity was
      evaluated with histochemical staining to assess tissue specific expression and
      distribution, and with quantitative, spectrofluometric assays to measure degree
      of activation. The evaluation of global changes in the Arabidopsis genome in
      response to exposure to high magnetic fields was facilitated with Affymetrix Gene
      Chip microarrays. Quantitative analyses of gene expression were performed with
      quantitative real-time polymerase-chain-reaction (qRT-PCR). RESULTS: Field
      strengths in excess of about 15 Tesla induce expression of the Adh/GUS transgene
      in the roots and leaves. From the microarray analyses that surveyed 8000 genes,
      114 genes were differentially expressed to a degree greater than 2.5 fold over
      the control. These results were quantitatively corroborated by qRT-PCR
      examination of 4 of the 114 genes. CONCLUSION: The data suggest that magnetic
      fields in excess of 15 Tesla have far-reaching effect on the genome. The wide
      spread induction of stress-related genes and transcription factors, and a
      depression of genes associated with cell wall metabolism, are prominent examples.
      The roles of magnetic field orientation of macromolecules and magnetophoretic
      effects are discussed as possible factors that contribute to the mounting of this
      response.

PMID- 17187666
TI  - Kinetic modeling of tumor growth and dissemination in the craniospinal axis:
      implications for craniospinal irradiation.
AB  - BACKGROUND: Medulloblastoma and other types of tumors that gain access to the
      cerebrospinal fluid can spread throughout the craniospinal axis. The purpose of
      this study was to devise a simple multi-compartment kinetic model using
      established tumor cell growth and treatment sensitivity parameters to model the
      complications of this spread as well as the impact of treatment with craniospinal
      radiotherapy. METHODS: A two-compartment mathematical model was constructed. Rate
      constants were derived from previously published work and the model used to
      predict outcomes for various clinical scenarios. RESULTS: The model is simple and
      with the use of known and estimated clinical parameters is consistent with known
      clinical outcomes. Treatment outcomes are critically dependent upon the duration
      of the treatment break and the radiosensitivity of the tumor. Cross-plot analyses
      serve as an estimate of likelihood of cure as a function of these and other
      factors. CONCLUSION: The model accurately describes known clinical outcomes for
      patients with medulloblastoma. It can help guide treatment decisions for
      radiation oncologists treating patients with this disease. Incorporation of other
      treatment modalities, such as chemotherapy, that enhance radiation sensitivity
      and/or reduce tumor burden, are predicted to significantly increase the
      probability of cure.

PMID- 17187668
TI  - How repetitive are genomes?
AB  - BACKGROUND: Genome sequences vary strongly in their repetitiveness and the causes
      for this are still debated. Here we propose a novel measure of genome
      repetitiveness, the index of repetitiveness, Ir, which can be computed in time
      proportional to the length of the sequences analyzed. We apply it to 336 genomes
      from all three domains of life. RESULTS: The expected value of Ir is zero for
      random sequences of any G/C content and greater than zero for sequences with
      excess repeats. We find that the Ir of archaea is significantly smaller than that
      of eubacteria, which in turn is smaller than that of eukaryotes. Mouse
      chromosomes have a significantly higher Ir than human chromosomes and within each
      genome the Y chromosome is most repetitive. A sliding window analysis reveals
      that the human HOXA cluster and two surrounding genes are characterized by local
      minima in Ir. A program for calculating the Ir is freely available at
      http://adenine.biz.fh-weihenstephan.de/ir/. CONCLUSION: The general measure of
      DNA repetitiveness proposed in this paper can be efficiently computed on a
      genomic scale. This reveals a broad spectrum of repetitiveness among diverse
      genomes which agrees qualitatively with previous studies of repeat content. A
      sliding window analysis helps to analyze the intragenomic distribution of
      repeats.

PMID- 17187669
TI  - Feeding by numbers: an ethnographic study of how breastfeeding women understand
      their babies' weight charts.
AB  - BACKGROUND: Weighing breastfed babies has been the subject of some controversy as
      the previous international growth chart was largely based on data from infants
      fed infant formula. The concern that professionals may be misled by the charts
      into suggesting to mothers that they supplement unnecessarily was a major impetus
      for the World Health Organization's investment in a new growth chart. Evidence of
      interpretation in practice has been scant. METHODS: An ethnographic study was
      conducted in a town in the Northwest of England to investigate this issue. In the
      first phase, women and health visitors were observed in the well-child clinic
      during clinic sessions and breastfeeding group meetings. In the second phase,
      longitudinal interviews with 14 women were conducted. Each woman was interviewed
      up to three times in the first six months after the birth of her baby, with a
      total of 35 interviews. RESULTS: Mothers and health visitors focussed on weight
      gain with frequent weighing and attention to even minor fluctuations of the
      plotted line being evident. Women felt it important to ensure their baby's weight
      followed a centile, and preferred for this to be the fiftieth centile.
      Interventions included giving infant formula and solids as well as changing what
      the mother ate and drank. Women also described how they worried about their
      baby's weight. Little effective support by health professionals with
      breastfeeding technique was observed. CONCLUSION: Babies were weighed more often
      than officially recommended, with weighing and plotting being at the core of each
      clinic visit. The plotted weight chart exerted a powerful influence on both
      women's and health visitors' understanding of the adequacy of breastfeeding. They
      appeared to rate the regular progression of weight gains along the chart centiles
      more highly than continued or exclusive breastfeeding. Thus weighing and visual
      charting of weight constituted a form of surveillance under the medical gaze,
      with mothers actively participating in self monitoring of their babies.
      Interventions, by mothers and health visitors, were targeted towards increasing
      weight gain rather than improving breastfeeding effectiveness. Improvements in
      training are needed for health visitors in weighing techniques, assessing growth
      patterns--particularly of breastfed babies--and in giving information to women,
      if the practice of routine weight monitoring is to support rather than undermine
      breastfeeding.

PMID- 17187671
TI  - Organ procurement organizations Internet enrollment for organ donation:
      abandoning informed consent.
AB  - BACKGROUND: Requirements for organ donation after cardiac or imminent death have
      been introduced to address the transplantable organs shortage in the United
      States. Organ procurement organizations (OPOs) increasingly use the Internet for
      organ donation consent. METHODS: An analysis of OPO Web sites available to the
      public for enrollment and consent for organ donation. The Web sites and consent
      forms were examined for the minimal information recommended by the United States
      Department of Health and Human Services for informed consent. Content scores were
      calculated as percentages of data elements in four information categories: donor
      knowledge, donor consent reinforcement, donation promotion, and informed consent.
      RESULTS: There were 60 Web sites for organ donation enrollment serving the 52
      states. The median percent (10 percentile-90 percentile) content scores of the
      Web sites for donor knowledge, donor consent reinforcement, and donation
      promotion were 33% (20-47), 79% (57-86), and 75% (50-100), respectively. The
      informed consent score was 0% (0-33). The content scores for donor knowledge and
      informed consent were significantly lower than donor consent reinforcement and
      donation promotion for all Web sites (P < .05). The content scores for the four
      categories were similar among the 11 regions of the United Network for Organ
      Sharing. CONCLUSION: The Web sites and consent forms for public enrollment in
      organ donation do not fulfill the necessary requirements for informed consent.
      The Web sites predominantly provide positive reinforcement and promotional
      information rather than the transparent disclosure of organ donation process.
      Independent regulatory oversight is essential to ensure that Internet enrollment
      for organ donation complies with legal and ethical standards for informed
      consent.

PMID- 17187670
TI  - The role of cholesterol and sphingolipids in chemokine receptor function and HIV
      1 envelope glycoprotein-mediated fusion.
AB  - BACKGROUND: HIV-1 entry into cells is a multifaceted process involving target
      cell CD4 and the chemokine receptors, CXCR4 or CCR5. The lipid composition of the
      host cell plays a significant role in the HIV fusion process as it orchestrates
      the appropriate disposition of CD4 and co-receptors required for HIV-1 envelope
      glycoprotein (Env)-mediated fusion. The cell membrane is primarily composed of
      sphingolipids and cholesterol. The effects of lipid modulation on CD4 disposition
      in the membrane and their role in HIV-1 entry have extensively been studied. To
      focus on the role of lipid composition on chemokine receptor function, we have by
      passed the CD4 requirement for HIV-1 Env-mediated fusion by using a CD4
      independent strain of HIV-1 Env. RESULTS: Cell fusion mediated by a CD4
      independent strain of HIV-1 Env was monitored by observing dye transfer between
      Env-expressing cells and NIH3T3 cells bearing CXCR4 or CCR5 in the presence or
      absence of CD4. Chemokine receptor signaling was assessed by monitoring changes
      in intracellular [Ca2+] mobilization induced by CCR5 or CXCR4 ligand. To modulate
      target membrane cholesterol or sphingolipids we used Methyl-beta-cyclodextrin
      (MbetaCD) or 1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP),
      respectively. Treatment of the target cells with these agents did not change the
      levels of CD4 or CXCR4, but reduced levels of CCR5 on the cell surface. Chemokine
      receptor signalling was inhibited by cholesterol removal but not by treatment
      with PPMP. HIV-1 Env mediated fusion was inhibited by >50% by cholesterol
      removal. Overall, PPMP treatment appeared to slow down the rates of CD4
      independent HIV-1 Env-mediated Fusion. However, in the case of CXCR4-dependent
      fusion, the differences between untreated and PPMP-treated cells did not appear
      to be significant. CONCLUSION: Although modulation of cholesterol and
      sphingolipids has similar effects on CD4-dependent HIV-1 Env-mediated fusion,
      sphingolipid modulation had little effect on CD4-independent HIV-1 Env-mediated
      fusion. Chemokine receptor function remained intact following treatment of cells
      with PPMP. Therefore such treatment may be considered a more suitable agent to
      inhibit CD4 dependent HIV-1 infection.

PMID- 17187672
TI  - Parity and breast cancer risk among BRCA1 and BRCA2 mutation carriers.
AB  - INTRODUCTION: Increasing parity and age at first full-term pregnancy are
      established risk factors for breast cancer in the general population. However,
      their effects among BRCA1 and BRCA2 mutation carriers is still under debate. We
      used retrospective data on BRCA1 and BRCA2 mutation carriers from the UK to
      assess the effects of parity-related variables on breast cancer risk. METHODS:
      The data set included 457 mutation carriers who developed breast cancer (cases)
      and 332 healthy mutation carriers (controls), ascertained through families seen
      in genetic clinics. Hazard ratios were estimated by using a weighted cohort
      approach. RESULTS: Parous BRCA1 and BRCA2 mutation carriers were at a
      significantly lower risk of developing breast cancer (hazard ratio 0.54, 95%
      confidence interval 0.37 to 0.81; p = 0.002). The protective effect was observed
      only among carriers who were older than 40 years. Increasing age at first live
      birth was associated with an increased breast cancer risk among BRCA2 mutation
      carriers (p trend = 0.002) but not BRCA1 carriers. However, the analysis by age
      at first live birth was based on small numbers. CONCLUSION: The results suggest
      that the relative risks of breast cancer associated with parity among BRCA1 and
      BRCA2 mutation carriers may be similar to those in the general population and
      that reproductive history may be used to improve risk prediction in carriers.

PMID- 17187674
TI  - Relationship between inflammatory markers, metabolic and anthropometric variables
      in the Caribbean type 2 diabetic patients with and without microvascular
      complications.
AB  - BACKGROUND: Serum sialic acid and C reactive protein are the markers for
      inflammation. The main objective of this study was to determine the sialic acid
      level in Caribbean type 2 diabetic patients with and without microvascular
      complications and its relationship with metabolic and anthropometric variables.
      RESEARCH DESIGN AND METHODS: The Caribbean subjects aged 15-60 years with type 2
      diabetes were recruited for the study. Fasting venous blood samples were
      collected from 162 subjects of which 44 were healthy individuals, 44 were of type
      2 diabetes, 44 were of type 2 diabetes with nephropathy and 30 were of diabetes
      with retinopathy. Simultaneously urine samples were also collected from each of
      the subjects. All the blood samples were processed for lipid profile, glucose,
      HbA1C, C-reactive protein and sialic acid. The urine samples were analysed for
      sialic acid and microalbumin. RESULTS: Serum sialic acid concentrations were
      significantly higher among diabetic subjects (66.0 +/- 11.7 mg %) as compared to
      controls (55.2 +/- 8.3 mg %). There was a significantly increasing trend of serum
      sialic acid with severity of nephropathy (71.6 +/- 23.6 mg %) and degree of
      urinary albumin excretion (794.3 +/- 805.9). The diabetic retinopathy patients
      also demonstrated significantly higher values of serum sialic acid (77.9 +/-
      29.0) and urine microalbumin (351.1 +/- 559.9). Elevated serum sialic acid
      microalbumin concentrations were associated with cardiovascular risk factors such
      as hypertension, increased waist to hip ratios. (P < 0.05). Sialic acid had no
      correlation with CRP or any component of the lipid profile. CONCLUSION: The
      increased serum sialic acid and microalbumin were strongly related to the
      presence of microvascular complications like diabetic nephropathy and diabetic
      retinopathy and cardiovascular risk factors like hypertension and waist to hip
      ratios in Caribbean type-2 diabetic patients. The serum sialic acid may be used
      as an inflammatory marker and possible indicator of microvascular complications
      in type-2 diabetic patients.

PMID- 17187673
TI  - Some considerations in the design and interpretation of antimalarial drug trials
      in uncomplicated falciparum malaria.
AB  - BACKGROUND: Treatments for uncomplicated falciparum malaria should have high cure
      rates. The World Health Organization has recently set a target cure rate of 95%
      assessed at 28 days. The use of more effective drugs, with longer periods of
      patient follow-up, and parasite genotyping to distinguish recrudescence from
      reinfection raise issues related to the design and interpretation of antimalarial
      treatment trials in uncomplicated falciparum malaria which are discussed here.
      METHODS: The importance of adequate follow-up is presented and the advantages and
      disadvantages of non-inferiority trials are discussed. The different methods of
      interpreting trial results are described, and the difficulties created by loss to
      follow-up and missing or indeterminate genotyping results are reviewed.
      CONCLUSION: To characterize cure rates adequately assessment of antimalarial drug
      efficacy in uncomplicated malaria requires a minimum of 28 days and as much as 63
      days follow-up after starting treatment. The longer the duration of follow-up in
      community-based assessments, the greater is the risk that this will be
      incomplete, and in endemic areas, the greater is the probability of reinfection.
      Recrudescence can be distinguished from reinfection using PCR genotyping but
      there are commonly missing or indeterminate results. There is no consensus on how
      these data should be analysed, and so a variety of approaches have been employed.
      It is argued that the correct approach to analysing antimalarial drug efficacy
      assessments is survival analysis, and patients with missing or indeterminate PCR
      results should either be censored from the analysis, or if there are sufficient
      data, results should be adjusted based on the identified ratio of new infections
      to recrudescences at the time of recurrent parasitaemia. Where the estimated cure
      rates with currently recommended treatments exceed 95%, individual comparisons
      with new regimens should generally be designed as non-inferiority trials with
      sample sizes sufficient to determine adequate precision of cure rate estimates
      (such that the lower 95% confidence interval bound exceeds 90%).

PMID- 17187675
TI  - Development and validation of vectors containing multiple siRNA expression
      cassettes for maximizing the efficiency of gene silencing.
AB  - BACKGROUND: RNA interference (RNAi) was originally identified as a biological
      process in which short double-stranded RNA (dsRNA) suppress the expression of
      genes complimentary to the dsRNA. This cellular intrinsic gene silencing
      mechanism has subsequently been developed as a useful tool for studies of gene
      function. A major strategy for producing small interfering RNA (siRNA) in
      cultured cells involves the use of siRNA expression vectors in which a RNA
      polymerase III (Pol III) promoter and transcription stop signal are designed to
      constitute a functional siRNA expression cassette for production of siRNA.
      However, most of the available vectors contain only one siRNA expression
      cassette. RESULTS: In order to maximize the efficiency and versatility of the
      vector-based siRNA approach, we have developed vectors containing multiple (up to
      six) tandem siRNA expression cassettes. Moreover, we demonstrated that these
      vectors can be used not only to produce different siRNA to simultaneously
      suppress the expression of multiple genes but also to maximize the silencing of a
      single gene. CONCLUSION: The vectors containing multiple siRNA expression
      cassettes can serve as useful tools for maximizing the efficiency of gene
      silencing.

PMID- 17187677
TI  - HaploRec: efficient and accurate large-scale reconstruction of haplotypes.
AB  - BACKGROUND: Haplotypes extracted from human DNA can be used for gene mapping and
      other analysis of genetic patterns within and across populations. A fundamental
      problem is, however, that current practical laboratory methods do not give
      haplotype information. Estimation of phased haplotypes of unrelated individuals
      given their unphased genotypes is known as the haplotype reconstruction or
      phasing problem. RESULTS: We define three novel statistical models and give an
      efficient algorithm for haplotype reconstruction, jointly called HaploRec.
      HaploRec is based on exploiting local regularities conserved in haplotypes: it
      reconstructs haplotypes so that they have maximal local coherence. This approach-
      not assuming statistical dependence for remotely located markers--has two useful
      properties: it is well-suited for sparse marker maps, such as those used in gene
      mapping, and it can actually take advantage of long maps. CONCLUSION: Our
      experimental results with simulated and real data show that HaploRec is a
      powerful method for the large scale haplotyping needed in association studies.
      With sample sizes large enough for gene mapping it appeared to be the best
      compared to all other tested methods (Phase, fastPhase, PL-EM, Snphap, Gerbil;
      simulated data), with small samples it was competitive with the best available
      methods (real data). HaploRec is several orders of magnitude faster than Phase
      and comparable to the other methods; the running times are roughly linear in the
      number of subjects and the number of markers. HaploRec is publicly available at
      http://www.cs.helsinki.fi/group/genetics/haplotyping.html.

PMID- 17187676
TI  - Identification of ciliary and ciliopathy genes in Caenorhabditis elegans through
      comparative genomics.
AB  - BACKGROUND: The recent availability of genome sequences of multiple related
      Caenorhabditis species has made it possible to identify, using comparative
      genomics, similarly transcribed genes in Caenorhabditis elegans and its sister
      species. Taking this approach, we have identified numerous novel ciliary genes in
      C. elegans, some of which may be orthologs of unidentified human ciliopathy
      genes. RESULTS: By screening for genes possessing canonical X-box sequences in
      promoters of three Caenorhabditis species, namely C. elegans, C. briggsae and C.
      remanei, we identified 93 genes (including known X-box regulated genes) that
      encode putative components of ciliated neurons in C. elegans and are subject to
      the same regulatory control. For many of these genes, restricted anatomical
      expression in ciliated cells was confirmed, and control of transcription by the
      ciliogenic DAF-19 RFX transcription factor was demonstrated by comparative
      transcriptional profiling of different tissue types and of daf-19(+) and daf-19(
      ) animals. Finally, we demonstrate that the dye-filling defect of dyf-5(mn400)
      animals, which is indicative of compromised exposure of cilia to the environment,
      is caused by a nonsense mutation in the serine/threonine protein kinase gene
      M04C9.5. CONCLUSION: Our comparative genomics-based predictions may be useful for
      identifying genes involved in human ciliopathies, including Bardet-Biedl Syndrome
      (BBS), since the C. elegans orthologs of known human BBS genes contain X-box
      motifs and are required for normal dye filling in C. elegans ciliated neurons.

PMID- 17187678
TI  - On the activity loss of hydrolases in organic solvents: II. a mechanistic study
      of subtilisin Carlsberg.
AB  - BACKGROUND: Enzymes have been extensively used in organic solvents to catalyze a
      variety of transformations of biological and industrial significance. It has been
      generally accepted that in dry aprotic organic solvents, enzymes are kinetically
      trapped in their conformation due to the high-energy barrier needed for them to
      unfold, suggesting that in such media they should remain catalytically active for
      long periods. However, recent studies on a variety of enzymes demonstrate that
      their initial high activity is severely reduced after exposure to organic
      solvents for several hours. It was speculated that this could be due to
      structural perturbations, changes of the enzyme's pH memory, enzyme aggregation,
      or dehydration due to water removal by the solvents. Herein, we systematically
      study the possible causes for this undesirable activity loss in 1,4-dioxane.
      RESULTS: As model enzyme, we employed the protease subtilisin Carlsberg, prepared
      by lyophilization and colyophilization with the additive methyl-beta-cyclodextrin
      (MbetaCD). Our results exclude a mechanism involving a change in ionization state
      of the enzyme, since the enzyme activity shows a similar pH dependence before and
      after incubation for 5 days in 1,4-dioxane. No apparent secondary or tertiary
      structural perturbations resulting from prolonged exposure in this solvent were
      detected. Furthermore, active site titration revealed that the number of active
      sites remained constant during incubation. Additionally, the hydration level of
      the enzyme does not seem to affect its stability. Electron paramagnetic resonance
      spectroscopy studies revealed no substantial increase in the rotational freedom
      of a paramagnetic nitroxide inhibitor bound to the active site (a spin-label)
      during incubation in neat 1,4-dioxane, when the water activity was kept constant
      using BaBr2 hydrated salts. Incubation was also accompanied by a substantial
      decrease in Vmax/KM. CONCLUSION: These results exclude some of the most obvious
      causes for the observed low enzyme storage stability in 1,4-dioxane, mainly
      structural, dynamics and ionization state changes. The most likely explanation is
      possible rearrangement of water molecules within the enzyme that could affect its
      dielectric environment. However, other mechanisms, such as small distortions
      around the active site or rearrangement of counter ions, cannot be excluded at
      this time.

PMID- 17187679
TI  - Identification of poly(ADP-ribose)polymerase-1 and Ku70/Ku80 as transcriptional
      regulators of S100A9 gene expression.
AB  - BACKGROUND: S100 proteins, a multigenic family of non-ubiquitous cytoplasmic Ca2+
      binding proteins, have been linked to human pathologies in recent years.
      Dysregulated expression of S100 proteins, including S100A9, has been reported in
      the epidermis as a response to stress and in association with neoplastic
      disorders. Recently, we characterized a regulatory element within the S100A9
      promotor, referred to as MRE that drives the S100A9 gene expression in a cell
      type-specific, activation- and differentiation-dependent manner (Kerkhoff et al.
      (2002) J. Biol. Chem. 277, 41879-41887). RESULTS: In the present study, we
      investigated transcription factors that bind to MRE. Using the MRE motif for a
      pull-down assay, poly(ADP-ribose)polymerase-1 (PARP-1) and the heterodimeric
      complex Ku70/Ku80 were identified by mass spectrometry and confirmed by chromatin
      immunoprecipitation. Furthermore, TPA-induced S100A9 gene expression in HaCaT
      keratinocytes was blocked after the pharmacologic inhibition of PARP-1 with 1,5
      isoquinolinediol (DiQ). CONCLUSION: The candidates, poly(ADP-ribose)polymerase-1
      (PARP-1) and the heterodimeric complex Ku70/Ku80, are known to participate in
      inflammatory disorders as well as tumorgenesis. The latter may indicate a
      possible link between S100 and inflammation-associated cancer.

PMID- 17187681
TI  - Reported food intake and distribution of body fat: a repeated cross-sectional
      study.
AB  - BACKGROUND: Body mass, as well as distribution of body fat, are predictors of
      both diabetes and cardiovascular disease. In Northern Sweden, despite a marked
      increase in average body mass, prevalence of diabetes was stagnant and myocardial
      infarctions decreased. A more favourable distribution of body fat is a possible
      contributing factor. This study investigates the relative importance of
      individual food items for time trends in waist circumference (WC) and hip
      circumference (HC) on a population level. METHODS: Independent cross-sectional
      surveys conducted in 1986, 1990, 1994 and 1999 in the two northernmost counties
      of Sweden with a common population of 250,000. Randomly selected age stratified
      samples, altogether 2982 men and 3087 women aged 25-64 years. Questionnaires were
      completed and anthropometric measurements taken. For each food item, associations
      between frequency of consumption and waist and hip circumferences were estimated.
      Partial regression coefficients for every level of reported intake were
      multiplied with differences in proportion of the population reporting the
      corresponding levels of intake in 1986 and 1999. The sum of these product terms
      for every food item was the respective estimated impact on mean circumference.
      RESULTS: Time trends in reported food consumption associated with the more
      favourable gynoid distribution of adipose tissue were increased use of vegetable
      oil, pasta and 1.5% fat milk. Trends associated with abdominal obesity were
      increased consumption of beer in men and higher intake of hamburgers and French
      fried potatoes in women. CONCLUSION: Food trends as markers of time trends in
      body fat distribution have been identified. The method is a complement to
      conventional approaches to establish associations between food intake and disease
      risk on a population level.

PMID- 17187680
TI  - Macrophage invasion contributes to degeneration of stria vascularis in Pendred
      syndrome mouse model.
AB  - BACKGROUND: Pendred syndrome, an autosomal-recessive disorder characterized by
      deafness and goiter, is caused by a mutation of SLC26A4, which codes for the
      anion exchanger pendrin. We investigated the relationship between pendrin
      expression and deafness using mice that have (Slc26a4+/+ or Slc26a4+/-) or lack
      (Slc26a4-/-) a complete Slc26a4 gene. Previously, we reported that stria
      vascularis of adult Slc26a4-/- mice is hyperpigmented and that marginal cells
      appear disorganized. Here we determine the time course of hyperpigmentation and
      marginal cell disorganization, and test the hypothesis that inflammation
      contributes to this tissue degeneration. METHODS: Slc26a4-/- and age-matched
      control (Slc26a4+/+ or Slc26a4+/-) mice were studied at four postnatal (P)
      developmental stages: before and after the age that marks the onset of hearing
      (P10 and P15, respectively), after weaning (P28-41) and adult (P74-170).
      Degeneration and hyperpigmentation stria vascularis was evaluated by confocal
      microscopy. Gene expression in stria vascularis was analyzed by microarray and
      quantitative RT-PCR. In addition, the expression of a select group of genes was
      quantified in spiral ligament, spleen and liver to evaluate whether expression
      changes seen in stria vascularis are specific for stria vascularis or systemic in
      nature. RESULTS: Degeneration of stria vascularis defined as hyperpigmentation
      and marginal cells disorganization was not seen at P10 or P15, but occurred after
      weaning and was associated with staining for CD68, a marker for macrophages.
      Marginal cells in Slc26a4-/-, however, had a larger apical surface area at P10
      and P15. No difference in the expression of Lyzs, C3 and Cd45 was found in stria
      vascularis of P15 Slc26a4+/- and Slc26a4-/- mice. However, differences in
      expression were found after weaning and in adult mice. No difference in the
      expression of markers for acute inflammation, including Il1a, Il6, Il12a, Nos2
      and Nos3 were found at P15, after weaning or in adults. The expression of
      macrophage markers including Ptprc (= Cd45), Cd68, Cd83, Lyzs, Lgals3 (= Mac2
      antigen), Msr2, Cathepsins B, S, and K (Ctsb, Ctss, Ctsk) and complement
      components C1r, C3 and C4 was significantly increased in stria vascularis of
      adult Slc26a4-/- mice compared to Slc26a4+/+ mice. Expression of macrophage
      markers Cd45 and Cd84 and complement components C1r and C3 was increased in stria
      vascularis but not in spiral ligament, liver or spleen of Slc26a4-/- compared to
      Slc26a4+/- mice. The expression of Lyzs was increased in stria vascularis and
      spiral ligament but not in liver or spleen. CONCLUSION: The data demonstrate that
      hyperpigmentation of stria vascularis and marginal cell reorganization in Slc26a4
      /- mice occur after weaning, coinciding with an invasion of macrophages. The data
      suggest that macrophage invasion contributes to tissue degeneration in stria
      vascularis, and that macrophage invasion is restricted to stria vascularis and is
      not systemic in nature. The delayed onset of degeneration of stria vascularis
      suggests that a window of opportunity exists to restore/preserve hearing in mice
      and therefore possibly in humans suffering from Pendred syndrome.

PMID- 17187682
TI  - Reactive oxygen species induce expression of vascular endothelial growth factor
      in chondrocytes and human articular cartilage explants.
AB  - Vascular endothelial growth factor (VEGF) promotes cartilage-degrading pathways,
      and there is evidence for the involvement of reactive oxygen species (ROS) in
      cartilage degeneration. However, a relationship between ROS and VEGF has not been
      reported. Here, we investigate whether the expression of VEGF is modulated by
      ROS. Aspirates of synovial fluid from patients with osteoarthritis (OA) were
      examined for intra-articular VEGF using ELISA. Immortalized C28/I2 chondrocytes
      and human knee cartilage explants were exposed to phorbol myristate acetate (PMA;
      0-20 microg/ml), which is a ROS inducer, or 3-morpholino-sydnonimine
      hydrochloride (SIN-1; 0-20 microM), which is a ROS donor. The levels of VEGF
      protein and nitric oxide (NO) production were determined in the medium
      supernatant, using ELISA and Griess reagent, respectively. Gene expression of
      VEGF-121 and VEGF-165 was determined by splice variant RT-PCR. Expression of VEGF
      and VEGF receptors (VEGFR-1 and VEGFR-2) was quantified by real-time RT-PCR.
      Synovial fluid from OA patients revealed markedly elevated levels of VEGF. Common
      RT-PCR revealed that the splice variants were present in both immortalized
      chondrocytes and cartilage discs. In immortalized chondrocytes, stimulation with
      PMA or SIN-1 caused increases in the levels of VEGF, VEGFR-1 and VEGFR-2 mRNA
      expression. Cartilage explants produced similar results, but VEGFR-1 was only
      detectable after stimulation with SIN-1. Stimulation with PMA or SIN-1 resulted
      in a dose-dependent upregulation of the VEGF protein (as determined using ELISA)
      and an increase in the level of NO in the medium. Our findings indicate ROS
      mediated induction of VEGF and VEGF receptors in chondrocytes and cartilage
      explants. These results demonstrate a relationship between ROS and VEGF as
      multiplex mediators in articular cartilage degeneration.

PMID- 17187683
TI  - CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation
      for severe adult respiratory failure.
AB  - BACKGROUND: An estimated 350 adults develop severe, but potentially reversible
      respiratory failure in the UK annually. Current management uses intermittent
      positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can
      prevent lung recovery. An alternative treatment, extracorporeal membrane
      oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas
      exchange, allowing ventilator settings to be reduced. While extracorporeal
      membrane oxygenation is proven to result in improved outcome when compared to
      conventional ventilation in neonates with severe respiratory failure, there is
      currently no good evidence from randomised controlled trials to compare these
      managements for important clinical outcomes in adults, although evidence from
      case series is promising. METHODS/DESIGN: The aim of the randomised controlled
      trial of Conventional ventilatory support vs extracorporeal membrane oxygenation
      for severe adult respiratory failure (CESAR) is to assess whether, for patients
      with severe, but potentially reversible, respiratory failure, extracorporeal
      membrane oxygenation will increase the rate of survival without severe disability
      ('confined to bed' and 'unable to wash or dress') by six months post
      randomisation, and be cost effective from the viewpoints of the NHS and society,
      compared to conventional ventilatory support. Following assent from a relative,
      adults (18-65 years) with severe, but potentially reversible, respiratory failure
      (Murray score >/= 3.0 or hypercapnea with pH < 7.2) will be randomised for
      consideration of extracorporeal membrane oxygenation at Glenfield Hospital,
      Leicester or continuing conventional care in a centre providing a high standard
      of conventional treatment. The central randomisation service will minimise by
      type of conventional treatment centre, age, duration of high pressure
      ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to
      ensure balance in key prognostic variables. Extracorporeal membrane oxygenation
      will not be available for patients meeting entry criteria outside the trial. 180
      patients will be recruited to have 80% power to be able to detect a one third
      reduction in the primary outcome from 65% at 5% level of statistical significance
      (2-sided test). Secondary outcomes include patient morbidity and health status at
      6 months. DISCUSSION: Analysis will be based on intention to treat. A concurrent
      economic evaluation will also be performed to compare the costs and outcomes of
      both treatments.

PMID- 17187684
TI  - Cholesteatoma of the external ear canal: etiological factors, symptoms and
      clinical findings in a series of 48 cases.
AB  - BACKGROUND: To evaluate symptoms, clinical findings, and etiological factors in
      external ear canal cholesteatoma (EECC). METHOD: Retrospective evaluation of
      clinical records of all consecutive patients with EECC in the period 1979 to 2005
      in a tertiary referral centre. Main outcome measures were incidence rates,
      classification according to causes, symptoms, extensions in the ear canal
      including adjacent structures, and possible etiological factors. RESULTS: Forty
      five patients were identified with 48 EECC. Overall incidence rate was 0.30 cases
      per year per 100,000 inhabitants. Twenty-five cases were primary, while 23 cases
      were secondary: postoperative (n = 9), postinflammatory (n = 5), postirradiatory
      (n = 7), and posttraumatic (n = 2). Primary EECC showed a right/left ratio of
      12/13 and presented with otalgia (n = 15), itching (n = 5), occlusion (n = 4),
      hearing loss (n = 3), fullness (n = 2), and otorrhea (n = 1). Similar symptoms
      were found in secondary EECC, but less pronounced. In total the temporomandibular
      joint was exposed in 11 cases, while the mastoid and middle ear was invaded in
      six and three cases, respectively. In one primary case the facial nerve was
      exposed and in a posttraumatic case the atticus and antrum were invaded. In
      primary EECC 48% of cases reported mechanical trauma. CONCLUSION: EECC is a rare
      condition with inconsistent and silent symptoms, whereas the extent of
      destruction may be pronounced. Otalgia was the predominant symptom and often
      related to extension into nearby structures. Whereas the aetiology of secondary
      EECC can be explained, the origin of primary EECC remains uncertain; smoking and
      minor trauma of the ear canal may predispose.

PMID- 17187685
TI  - Sexual behavior and experience of sexual coercion among secondary school students
      in three states in North Eastern Nigeria.
AB  - BACKGROUND: Interest in the reproductive health of adolescents continues to grow
      throughout the world. Few studies had explored the reproductive health knowledge,
      sexual behavior and experience of sexual coercion among secondary school students
      in North Eastern states of Nigeria. The objectives of this descriptive survey
      were to collect data to plan appropriate interventions that meet the reproductive
      health knowledge, service and skills needs of students in Bauchi, Borno and Gombe
      states. METHODS: Face-to-face interviews were conducted for 624 consenting
      students who were randomly selected from eighteen secondary schools using an 83
      item structured questionnaire. Data were collected on demographic profile,
      reproductive health knowledge, sexual behavior and experience of sexual coercion.
      RESULTS: The mean age of the respondents was 16.5 years. There were slightly more
      males (52%) than females (48%). Students' knowledge about reproductive health was
      generally low even though girls had better knowledge than boys. Thirteen percent
      of the entire students had had sexual experience; significantly more males (19%)
      than females (6%) had done so (p < 0.001). Among boys the age at sexual debut
      ranged from 10-26 with a mean of 15.7 and median of 16. By contrast, the age at
      first sex among girls ranged from 10 to 18 years with a mean and median of 16.1
      and 17 years respectively. Only 24% of those who were sexually active used a
      condom during their last sexual encounter. Overall 11% of the students reported
      that they had been tricked into having sex, 9% had experienced unwanted touch of
      breast and backside, and 5% reported rape. CONCLUSION: Students low reproductive
      health knowledge and involvement in risky sexual activities predispose them to
      undesirable reproductive health outcomes.

PMID- 17187686
TI  - The intra-articular use of ropivacaine for the control of post knee arthroscopy
      pain.
AB  - AIMS: The purpose of this prospective randomised study is to evaluate the
      efficacy, safety and the appropriate dose of the ropivacaine in the control of
      post-knee arthroscopy pain. METHODS: We randomised 60 patients in two groups to
      receive 10 ml/7.5 mg/ml ropivacaine (Group B) or 20 ml/7.5 mg/ml (Group A) at the
      end of a routine knee arthroscopy. We monitored the patient's blood pressure,
      heart rate, allergic reactions, headache, nausea, we assessed the pain using the
      visual analogue score at intervals of 1,2,3,4 and 6 hours after the operation.
      and we recorded the need for extra analgesia. RESULTS: The intraarticular use of
      the ropivacaine provided excellent control of pain after knee arthroscopy. At two
      hours post-operatively there wasn't any difference between the two groups.
      Afterwards, the Group A showed increased pain and need for supplementary
      medication. CONCLUSION: We believe that intraarticular use of ropivacaine is
      effective to reduce post-operative pain minimising the use of systematic
      analgesia.

PMID- 17187687
TI  - Structure of a conserved hypothetical protein SA1388 from S. aureus reveals a
      capped hexameric toroid with two PII domain lids and a dinuclear metal center.
AB  - BACKGROUND: The protein encoded by the SA1388 gene from Staphylococcus aureus was
      chosen for structure determination to elucidate its domain organization and
      confirm our earlier remote homology based prediction that it housed a nitrogen
      regulatory PII protein-like domain. SA1388 was predicted to contain a central PII
      like domain and two flanking regions, which together belong to the NIF3-like
      protein family. Proteins like SA1388 remain a poorly studied group and their
      structural characterization could guide future investigations aimed at
      understanding their function. RESULTS: The structure of SA1388 has been solved to
      2.0A resolution by single wavelength anomalous dispersion phasing method using
      selenium anomalous signals. It reveals a canonical NIF3-like fold containing two
      domains with a PII-like domain inserted in the middle of the polypeptide. The N
      and C terminal halves of the NIF3-like domains are involved in dimerization,
      while the PII domain forms trimeric contacts with symmetry related monomers.
      Overall, the NIF3-like domains of SA1388 are organized as a hexameric toroid
      similar to its homologs, E. coli ybgI and the hypothetical protein SP1609 from
      Streptococcus pneumoniae. The openings on either side of the toroid are partially
      covered by trimeric "lids" formed by the PII domains. The junction of the two
      NIF3 domains has two zinc ions bound at what appears to be a histidine rich
      active site. A well-defined electron density corresponding to an endogenously
      bound ligand of unknown identity is observed in close proximity to the metal
      site. CONCLUSION: SA1388 is the third member of the NIF3-like family of proteins
      to be structurally characterized, the other two also being hypothetical proteins
      of unknown function. The structure of SA1388 confirms our earlier prediction that
      the inserted domain that separates the two NIF3 domains adopts a PII-like fold
      and reveals an overall capped toroidal arrangement for the protein hexamer. The
      six PII-like domains form two trimeric "lids" that cap the central cavity of the
      toroid on either side and provide only small openings to allow regulated entry of
      small molecules into the occluded chamber. The presence of the electron density
      of the bound ligand may provide important clues on the likely function of NIF3
      like proteins.

PMID- 17187688
TI  - Benign intracranial hypertension associated to blood coagulation derangements.
AB  - BACKGROUND: Benign Intracranial Hypertension (BIH) may be caused, at least in
      part, by intracranial sinus thrombosis. Thrombosis is normally due to
      derangements in blood coagulation cascade which may predispose to abnormal
      clotting activation or deficiency in natural inhibitors' control. The aim of the
      study is to examine the strength of the association between risk factors for
      thrombosis and BIH. PATIENTS AND METHODS: The incidence of prothrombotic
      abnormalities among a randomly investigated cohort of 17 patients with BIH, was
      compared with 51 healthy subjects matched for sex, age, body mass index, height
      and social background. RESULTS: The number of subjects with protein C deficiency
      was significantly higher in patients than in controls (3 vs 1, p < .001; Fisher
      Exact Test). Moderate to high titers of anticardiolipin antibodies (beta2
      Glycoprotein type I) were found in 8 out of 17 patients. Increased plasma levels
      of prothrombin fragment 1+2, fibrinopeptide A (FPA), and PAI-1 were demonstrated
      in patients group (5.7 +/- 1.15 nM vs 0.45 +/- 0.35 nM; 8.7 +/- 2.5 ng/mL vs 2.2
      +/- 1.25 ng/mL; 45.7 +/- 12.5 ng/mL vs 8.5 +/- 6.7 ng/mL, respectively; p < .001;
      Fisher Exact Test). Gene polymorphisms for factor V Leiden mutation, prothrombin
      mutation 20210 A/G, MTHFR 677 C/T, PAI-1 4G/5G, ACE I/D were detected in 13
      patients. DISCUSSION: In agreement with other authors our data suggest a state of
      hypercoagulability in BIH associated with gene polymorphisms. Our findings also
      showed that mutations in cardiovascular genes significantly discriminate subjects
      with a BIH history. The association between coagulation and gene derangements,
      usually regarded to as cryptogenic, may suggest a possible pathogenetic mechanism
      in BIH. So, a prothrombotic tendency may exist that would, at least in part,
      explain some cases of BIH. Although based on a small population, these findings
      raise the exciting possibility of using these haemostatic factors as markers for
      selecting high-risk subjects in BIH disease.

PMID- 17187689
TI  - Proteomic alteration in gastic adenocarcinomas from Japanese patients.
AB  - BACKGROUND: Gastric adenocarcinomas comprise one of the common types of cancers
      in Asian countries including Japan. Comprehensive protein profiling of paired
      surgical specimens of primary gastric adenocarcinomas and nontumor mucosae
      derived from Japanese patients was carried out by means of two-dimensional gel
      electrophoresis (2D-EP) and liquid chromatography-electrospray ionic tandem mass
      spectrometry (LC-ESI-MS) to establish gastric cancer-specific proteins as
      putative clinical biomarkers and molecular targets for chemotherapy. RESULTS:
      Relatively common alterations in protein expression were revealed in the tumor
      tissues. Increases in manganese dismutase and nonhistone chromosomal protein HMG
      1 (HMG-1) were observed, while decreases in carbonic anhydrases I and II,
      glutatione-S-transferase and foveolin precursor (gastrokine-1) (FOV), an 18-kDa
      stomach-specific protein with putative tumor suppressor activity, were detected.
      RT-PCR analysis also revealed significant down-regulation of FOV mRNA expression
      in tumor tissues. CONCLUSION: A possible pathological role for down-regulation of
      FOV in gastric carcinogenesis was demonstrated. Evaluation of the specific
      decreases in gene and protein expression of FOV in patients may be utilized as
      clinical biomarkers for effective diagnosis and assessment of gastric cancer.

PMID- 17187690
TI  - Conservation of noncoding microsatellites in plants: implication for gene
      regulation.
AB  - BACKGROUND: Microsatellites are extremely common in plant genomes, and in
      particular, they are significantly enriched in the 5' noncoding regions. Although
      some 5' noncoding microsatellites involved in gene regulation have been
      described, the general properties of microsatellites as regulatory elements are
      still unknown. To address the question of microsatellites associated with
      regulatory elements, we have analyzed the conserved noncoding microsatellite
      sequences (CNMSs) in the 5' noncoding regions by inter- and intragenomic
      phylogenetic footprinting in the Arabidopsis and Brassica genomes. RESULTS: We
      identified 247 Arabidopsis-Brassica orthologous and 122 Arabidopsis paralogous
      CNMSs, representing 491 CT/GA and CTT/GAA repeats, which accounted for 10.6% of
      these types located in the 500-bp regions upstream of coding sequences in the
      Arabidopsis genome. Among these identified CNMSs, 18 microsatellites show high
      conservation in the regulatory regions of both orthologous and paralogous genes,
      and some of them also appear in the corresponding positions of more distant
      homologs in Arabidopsis, as well as in other plants. A computational scan of
      CNMSs for known cis-regulatory elements showed that light responsive elements
      were clustered in the region of CT/GA repeats, as well as salicylic acid
      responsive elements in the (CTT)n/(GAA)n sequences. Patterns of gene expression
      revealed that 70-80% of CNMS (CTT)n/(GAA)n associated genes were regulated by
      salicylic acid, which was consistent with the prediction of regulatory elements
      in silico. CONCLUSION: Our analyses showed that some noncoding microsatellites
      were conserved in plants and appeared to be ancient. These CNMSs served as
      regulatory elements involved in light and salicylic acid responses. Our findings
      might have implications in the common features of the over-represented
      microsatellites for gene regulation in plant-specific pathways.

PMID- 17187691
TI  - Recursive gene selection based on maximum margin criterion: a comparison with SVM
      RFE.
AB  - BACKGROUND: In class prediction problems using microarray data, gene selection is
      essential to improve the prediction accuracy and to identify potential marker
      genes for a disease. Among numerous existing methods for gene selection, support
      vector machine-based recursive feature elimination (SVM-RFE) has become one of
      the leading methods and is being widely used. The SVM-based approach performs
      gene selection using the weight vector of the hyperplane constructed by the
      samples on the margin. However, the performance can be easily affected by noise
      and outliers, when it is applied to noisy, small sample size microarray data.
      RESULTS: In this paper, we propose a recursive gene selection method using the
      discriminant vector of the maximum margin criterion (MMC), which is a variant of
      classical linear discriminant analysis (LDA). To overcome the computational
      drawback of classical LDA and the problem of high dimensionality, we present
      efficient and stable algorithms for MMC-based RFE (MMC-RFE). The MMC-RFE
      algorithms naturally extend to multi-class cases. The performance of MMC-RFE was
      extensively compared with that of SVM-RFE using nine cancer microarray datasets,
      including four multi-class datasets. CONCLUSION: Our extensive comparison has
      demonstrated that for binary-class datasets MMC-RFE tends to show intermediate
      performance between hard-margin SVM-RFE and SVM-RFE with a properly chosen soft
      margin parameter. Notably, MMC-RFE achieves significantly better performance with
      a smaller number of genes than SVM-RFE for multi-class datasets. The results
      suggest that MMC-RFE is less sensitive to noise and outliers due to the use of
      average margin, and thus may be useful for biomarker discovery from noisy data.

PMID- 17187693
TI  - Screening asymptomatic siblings for vesicoureteral reflux: sound science or
      religious rhetoric?
AB  - INTRODUCTION: Many urologists endorse the concept of screening asymptomatic
      siblings of children known to have vesicoureteral reflux. Others oppose screening
      until there is better evidence to justify the cost and potential morbidity of
      adopting a widespread screening program. METHODS: A literature review of the
      following topics was carried out: 1) screening programs in general; 2) reflux in
      general; 3) familial reflux; and 4) screening for familial reflux. RESULTS: The
      evidence supporting our traditional surgical and medical management strategies
      for reflux is weak. The evidence supporting screening is lacking. Public Health
      organizations do not address the issue of screening for this condition. Despite
      this, there is a significant body of peer reviewed literature and compelling
      expert opinion, in support of screening. Possible reasons for this are explored.
      CONCLUSIONS: A randomized controlled trial to definitively assess the utility of
      screening would be larger and more challenging to perform than any ever done in
      the history of this condition. Until such time that high quality evidence exists,
      screening of asymptomatic siblings will continue to be based upon our individual
      clinical experience and teachings, the morbidity of the index case, and
      socioeconomic factors. We must continue to re-evaluate our management strategies
      for this condition in light of new information as it accrues.

PMID- 17187694
TI  - Risk of post-operative intravesical mitomycin C instillation following
      transurethral bladder tumor resection.
AB  - Bladder cancer is the fifth most common cancer in the Western world and is on the
      rise. Most patients present with superficial disease and are treated by
      transurethral resection of bladder tumor. More than half of these patients
      experience recurrence with about 20% progressing to muscle invasive disease.
      Intravesical chemotherapy has been shown to decrease the risk of recurrence of
      bladder cancer. Mitomycin C has emerged as a major agent for an immediate post
      resection intravesical instillation. This article reviews the literature on the
      mode of action, rationale for immediate adjuvant treatment with Mitomycin C and
      adverse effects associated with its use.

PMID- 17187695
TI  - A randomized controlled trial comparing two educational booklets on prostate
      cancer.
AB  - PURPOSE: To compare the helpfulness of two educational aids or booklets on early
      stage prostate cancer. METHOD: Participating consecutive patients and a family
      member, in three centres, received one of two booklets, one produced by
      AstraZeneca (AZ), the other produced by us (CCE); the patient and family shared a
      booklet but were separate study participants. The primary outcome was the Purpose
      based Information Assessment completed after participants read their booklet;
      they rated the importance (4-point Likert scale) of six potential purposes for
      the information: to help organize their thoughts, understand their situations,
      decide on treatment, plan, provide emotional support to others, and discuss
      issues. Each participant then rated how helpful their booklet was (4-point Likert
      scale) in addressing each purpose they had rated above the lowest importance
      category. Participants mailed in their responses. RESULTS: Complete data were
      received from 308 (81%) of those who consented to the study: 152 in the CCE group
      and 156 in the AZ group. The CCE booklet was read for a longer time [chi(2) =
      28.61, p = 0.00] but was easier to find information in chi(2) = 7.6, p = 0.05].
      Although for each purpose, most readers rated each booklet in one of the top two
      (of four) helpfulness categories, the CCE booklet was rated more helpful for:
      organizing [chi(2) = 30.49, p = 0.00], understanding [chi(2) = 12.07, p = .007],
      deciding [chi(2) = 9.96, p = 0.02] and planning [chi(2) = 18.67, p = 0.00].
      CONCLUSIONS: High helpfulness ratings of both booklets suggest that patients
      benefit from education aids while differences in the booklet ratings suggest that
      aids are not equally helpful. The CCE booklet, the more helpful booklet of this
      study, is a systematically developed education aid available to urologists in
      Canada.

PMID- 17187696
TI  - Controversies in prostate cancer staging implementation at a tertiary cancer
      center.
AB  - OBJECTIVE: To assess accuracy of recorded prostate cancer stage after
      implementation of a quality assurance staging improvement plan. METHODS AND
      MATERIALS: Genitourinary multidisciplinary TNM staging guidelines were
      prospectively implemented. Educational programs for health records technicians
      (HRT) and clinicians preceded implementation of the new guidelines. Patient stage
      information was entered into the Oncology Patient Information System (OPIS) as
      part of the usual operations of the cancer center by an HRT. Physician and HRT
      auditors performed a subsequent quality assurance audit on 97 prostate cancer
      patients seen over a 2-month period. Assessment of staging accuracy and reasons
      for discrepancies between the OPIS stage and auditor stage were analyzed and
      reported. RESULTS: Fifty-four (52%) charts showed discrepancies between auditors.
      Of the fifty-four, twelve (22%) had discrepancies between OPIS and auditor,
      thirty (56%) showed discrepancies between auditors, and twelve (22%) had
      discrepancies between OPIS, physician auditor, and HRT auditor. Forty-three (41%)
      cases had no discrepancies. Reasons for discrepancies included: misinterpretation
      of the digital rectal examination (16/54), inappropriate use of TRUS/MRI (9/54)
      in staging, stage not assigned at initial diagnosis (9/54), misinterpretation of
      pathology (7/54), TNM staging confusion (4/54), OPIS update not performed (3/54),
      inappropriate use of biopsy data (3/54), disagreement between consultants (2/54),
      and misinterpretation of TURP result (1/54). Overall staging accuracy was 76% for
      OPIS, 65% for the physician auditor and 62% for the HRT auditor. CONCLUSIONS:
      Despite guidelines and educational interventions, computer registry staging
      accuracy remains an issue. On-going audit procedures are proposed to identify and
      correct both published and institutional staging guidelines.

PMID- 17187697
TI  - Prednisone monotherapy in asymptomatic hormone refractory prostate cancer.
AB  - BACKGROUND: Patients with advanced prostate cancer eventually cease to respond to
      hormonal therapy and thus progress to hormone refractory prostate cancer (HRPC).
      Prednisone has been used in this setting; however, limited data is available for
      this monotherapy in the asymptomatic HRPC population. OBJECTIVE: To evaluate the
      PSA response rate to prednisone in asymptomatic patients with hormone refractory
      prostate cancer (HRPC). Secondary objectives were to determine toxicity,
      predictors of response, and to determine overall survival of this population.
      METHODS: Patients with asymptomatic HRPC that were treated with low dose
      prednisone from April 1998 to 2003 were identified from the British Columbia
      Cancer Agency patient and pharmacy registries. Inclusion criteria were an ECOG
      Performance Status of 2 at the time of prednisone initiation, prior medical or
      surgical orchidectomy, a rising PSA, and no symptoms from prostate cancer.
      Demographic data, lab values, serial PSAs, and survival data were collected.
      Univariate analyses were performed to evaluate potential predictors of response.
      RESULTS: Forty-nine patients met the inclusion criteria. There was a 22.4%
      response rate to prednisone as defined by a 50% PSA decline. An additional 16.3%
      of patients had a PSA decline of < 50%. Ninety percent of patients had no
      documented side effects. PSA responders were more likely to have bony metastases
      (9/11 versus 17/38, p = 0.03) and lived longer (24.7 versus 15.4 months median
      survival p = 0.02). The median duration of response in the PSA responders was 4.3
      months (0.89-30). Of all PSA responders, 27% had a time to progression greater
      than 1 year and 45% did not require chemotherapy for the duration of the study.
      CONCLUSION: Prednisone monotherapy is well tolerated and is associated with a
      clinically relevant response rate in patients with asymptomatic HRPC. Prolonged
      time to progression and thus avoidance of more toxic chemotherapy is possible in
      some patients.

PMID- 17187698
TI  - Comparison of laparoscopic and open nephrectomy for adult polycystic kidney
      disease: operative challenges and technique.
AB  - OBJECTIVES: Autosomal dominant polycystic kidney disease an inherited systemic
      disorder is characterized by the development of multiple cysts in the kidneys and
      other organs. When nephrectomy is indicated, the laparoscopic approach is
      challenging due to the massive size of these kidneys. We present our technique
      and evaluate the surgical outcomes of laparoscopic versus open nephrectomy for
      patients with such condition. MATERIALS AND METHODS: A retrospective review was
      done for six laparoscopic and six open nephrectomies performed by two
      laparoscopic surgeons in two university hospitals between January 2004 and
      December 2004. Preoperative, intraoperative, and postoperative data are
      presented. A standard subcostal incision was used for the open cases while for
      the laparoscopic approach a 3-4-port transperitoneal laparoscopic approach was
      used to dissect the involved kidney, which is then removed intact or morcellated
      through pfannenstiel, midline, or expanded port site incision. RESULTS: The
      laparoscopic patients had a longer operative time with one major complication
      compared to the open group. On the other hand laparoscopic group achieved minimal
      blood loss, less narcotic requirement and a shorter hospital stay. No conversion
      to open required in the laparoscopy group. At a median follow up of 1 year no
      long-term complications reported in either groups. CONCLUSIONS: Laparoscopic
      nephrectomy for polycystic kidney disease is a feasible and safe alternative to
      open approach. In addition to low morbidity, other advantages of laparoscopic
      surgery also achieved in this subset of patients such as the ability to remove
      the dissected kidney through a small incision, reduced postoperative pain, short
      hospital stay, and excellent cosmesis.

PMID- 17187699
TI  - Presentation of a functional pituitary adenoma as a significant decrease in
      prostate-specific antigen level in a patient followed for prostate cancer.
AB  - The stimulatory role of testosterone in the production and release of prostate
      specific antigen (PSA) has been well characterized. Testosterone production by
      the testes is dependent on a functional hypothalamic-pituitary-gonadal axis. High
      prolactin levels have been shown to disrupt this axis, resulting in decreases in
      gonadotropins and testosterone levels. We report a patient with prostate cancer
      and elevated PSA levels followed with "watchful waiting" for several years who
      experienced a precipitous decrease in PSA level over a 3 month period. The
      patient was found to have an asymptomatic prolactin-secreting pituitary
      macroadenoma.

PMID- 17187700
TI  - Malignant cystic nephroma.
AB  - AIM: To describe a malignant cystic nephroma in an asymptomatic man. METHODS:
      Case report and review of the literature. RESULTS: A 60 year old white male
      presented with an incidentally discovered right perirenal mass. An MRI
      demonstrated a large perinephric encapsulated mass with diffuse heterogeneity.
      Patient underwent a radical nephrectomy and retroperitoneal node dissection.
      Histopathological analyses of the resected specimen revealed malignant cystic
      nephroma. CONCLUSION: This represents the first published report of this rare
      tumor in an adult patient.

PMID- 17187701
TI  - Subcutaneous reservoir placement during penile prosthesis implantation.
AB  - Currently, the prosthesis of choice for patients undergoing penile prosthesis
      surgery is a three piece inflatable device, as this provides optimal inflation
      and deflation when compared to a one or two piece prosthesis. However, prior
      pelvic surgery or radiation therapy can obliterate the retropubic space and make
      placement of the reservoir required for a three piece prosthesis difficult. We
      report a novel location for reservoir placement in a man who had undergone
      multiple pelvic surgeries after suffering a severe pelvic crush injury.

PMID- 17187702
TI  - Surgical modifications in bladder neck reconstruction and vesicourethral
      anastomosis during radical retropubic prostatectomy to reduce bladder neck
      contractures.
AB  - PURPOSE: We describe surgical modifications in radical retropubic prostatectomy
      (RRP) which have significantly reduced the incidence of bladder neck contractures
      (BNC). MATERIALS AND METHODS: Between March 1994-July 2005, 977 men underwent a
      RRP by a single surgeon. Group I comprised 548 patients operated upon July 1994
      December 1999, without the modifications described below. Group II comprised 429
      men operated upon January 2000-December 2004, with the following surgical
      modifications: 1) reconstruction of the bladder neck (BN) to a diameter of 28
      French; 2) placement of the posterior (6 o'clock) vesicourethral suture on mild
      traction before placing this suture into the bladder, allowing inspection and, if
      necessary, replacement of any of the previously placed sutures; 3) bladder
      displacement when tying the vesicourethral sutures which allows the sutures to be
      tied under direct vision and prevents incorporation of extraneous tissue. Data
      were retrospectively analyzed. RESULTS: Demographic data were comparable between
      groups. In group I, 31/548 (5.7%) developed a BNC compared to 1/429 (0.2%) in
      Group II, p < 0.001. Urinary continence (no pads/maximum of one light pad for
      security in 24 hours) at 12 months in the 32 patients who developed a BNC was
      worse when compared to patients who did not develop a BNC (58% versus 80%, p =
      0.003). After excluding the patients who developed a BNC, continence rates were
      comparable between both groups. The positive margin rate at the BN was not
      adversely affected by these modifications. CONCLUSIONS: Simple, easily applied
      modifications to the management of the BN and vesicourethral anastomosis can
      substantially reduce the incidence of BNC.

PMID- 17187703
TI  - The efficacy of the Dornier Doli S lithotripter for renal stones.
AB  - INTRODUCTION: There is little documentation of the efficacy of the Doli-S
      lithotripter. This study investigated the outcome of ESWL with the Doli-S
      lithotripter on previously untreated renal calculi. METHODS: Over a 12 month
      period, 105 consecutive patients with renal stones, treated by a single urologist
      were enrolled in the study. None of the stones were previously treated. Data
      gathered included stone characteristics and treatment characteristics. Treatment
      was to an endpoint of either fluoroscopically successful fragmentation or to 2500
      shockwaves. Patients were followed with KUBs, ultrasounds, or CT-KUBs to assess
      residual stone burden. Treatment success was defined as complete clearing of the
      calculus, or residual fragments of less than 3 mm. RESULTS: One hundred five
      patients were treated and 16 were lost to follow-up. One hundred nineteen stones
      in 89 patients were included in our analysis. Mean follow-up was 115 days. The
      average stone size (expressed as mean of two measured stone dimensions) was 7.8
      mm. After a single lithotripsy treatment, the overall treatment success rate was
      47.9%. The left kidney accounted for 58% of the treated stones. Treatment success
      was greater for left renal stones than right-sided stones (55.1% versus 38.0%, p
      = 0.033). There was no significant difference in treatment success rates for
      calyceal location of stones. Lower pole stones were treated successfully in 57.9%
      of cases. Smaller stones (3 mm-10 mm) were more successfully treated than larger
      stones (10 mm-20 mm) (55.6% versus 24.1%, p = < 0.001). CONCLUSIONS: Success
      rates for the Doli-S lithotripter for a single treatment of previously untreated
      renal stones ranged from 24%-58%, depending on stone size and location. These
      rates are lower than success rates reported for other lithotripters. Inferior
      pole calculi had a higher treatment success rate than previously reported.
      Factors associated with treatment success included smaller stone size, left-sided
      stones, and ease of fluoroscopic visualization.

PMID- 17187704
TI  - The burden of debt for Canadian dental students: part 4. The influence of debt on
      program and career decisions.
AB  - In the 3 previous papers of this 4-part series, we explored the issue of debt
      among dental students in Canada to analyze the factors influencing levels of
      debt. The information was obtained from a national survey of all dental students
      enrolled in Canadian dental schools during the 2003-2004 academic year. The aims
      of this fourth paper were to investigate the influence of debt upon career
      decisions after graduation and to comment on future directions for research into
      the impact of the rising costs of dental education and dental students'
      increasing debt levels. The results show that almost half of respondents found
      the costs of dental programs significantly higher than they anticipated. One
      third of the respondents indicated that their anticipated debt level upon
      graduation had influenced their choice of career path within dentistry. Although
      this study provides baseline information about the degree of and influences on
      the indebtedness of students currently enrolled in dental programs across Canada,
      much remains to be learned about the impact of the higher costs of dental
      education on potential applicants to dental school and the effect of increased
      educational debt on practising dentists.

PMID- 17187705
TI  - Patients with special health care needs in general and pediatric dental practices
      in Ontario.
AB  - The objective of this study was to determine the involvement of Ontario's general
      and pediatric dentists in providing care to patients with special health care
      needs (PSHCNs). A questionnaire was developed and sent to a randomly selected
      sample of general dentists and to all pediatric dentists in Ontario; response
      rates were 52% and 90%, respectively. Most general dentists and all pediatric
      dentists reported that they provided a full range of dental services to PSHCNs.
      Most (80%) general dentists treat PSHCNs of all ages, whereas 60% of pediatric
      dentists report only treating PSHCNs up to the age of 18 years. A majority of
      both groups report treating PSHCNs whose dental care is paid through various
      government-funded programs. Most general dentists received training in the
      treatment of PSHCNs in undergraduate dental school, and 40% reported taking
      continuing education courses in this area. Most pediatric dentists received this
      training during their advanced dental specialty training, and 29% reported taking
      continuing education courses in this area. The results of this survey appear to
      demonstrate that general and pediatric dentists in Ontario provide a full range
      of dental services to PSHCNs, treat patients with a variety of disabilities and
      of all ages and are interested in pursuing continuing education that focuses on
      the delivery of dental care to PSHCNs. However, the results may be inaccurate
      because of question design flaws and responder bias among the 52% of surveyed
      general dentists who returned their questionnaires.

PMID- 17187706
TI  - Rationale for socket preservation after extraction of a single-rooted tooth when
      planning for future implant placement.
AB  - After tooth extraction, the alveolar ridge will commonly decrease in volume and
      change morphologically. These changes are usually clinically significant and can
      make placement of a conventional bridge or an implant-supported crown difficult.
      If bone resorption is significant enough, then placement of an implant may become
      extremely challenging. Postextraction maintenance of the alveolar ridge minimizes
      residual ridge resorption and, thus, allows placement of an implant that
      satisfies esthetic and functional criteria. Recent advances in bone grafting
      materials and techniques allow the dentist to place implants in sites that were
      considered compromised in the past. This article focuses on the healing pattern
      of sockets, with and without the use of regenerative materials, and the rationale
      for preserving the dimensions of the extraction socket. Histologic and clinical
      evidence is reviewed to provide an in-depth understanding of the logic behind and
      value of socket preservation.

PMID- 17187707
TI  - Why does supragingival calculus form preferentially on the lingual surface of the
      6 lower anterior teeth?
AB  - Many authors have assumed that the reason supragingival calculus tends to form
      preferentially on the lingual surface of the 6 lower anterior teeth is because
      saliva from the adjacent submandibular ducts is a source of calcium and phosphate
      ions and because loss of CO2 as the saliva enters the mouth increases the local
      pH. However, the fluid phase of plaque in all locations is supersaturated with
      respect to the calcium phosphates in calculus and there is always a tendency for
      calculus to deposit, except after sugar consumption, when plaque pH may fall
      below the critical level and the plaque fluid becomes unsaturated. pH is least
      likely to fall below the critical level in plaque lingual to the lower anterior
      teeth, as this plaque is very thin, sugar concentration after sugar intake is
      lowest in that area and its clearance rate is fastest, and the high salivary film
      velocity there promotes loss of any acid formed in plaque. A high salivary film
      velocity also brings more salivary urea to the site, which facilitates plaque
      alkalinization. These factors all contribute to the development of shallow
      Stephan curves of short duration and together provide a more reasonable
      explanation for the fact that supragingival calculus deposition progresses most
      easily on the lingual surface of the lower anterior teeth.

PMID- 17187708
TI  - Transient loss of power of accommodation in 1 eye following inferior alveolar
      nerve block: report of 2 cases.
AB  - Unintended intravascular injection from inferior alveolar nerve blocks can result
      in frustrating distant complications affecting such structures as the middle ear
      and eyes. Possible complications affecting the eyes include blurring of vision,
      diplopia, mydriasis, palpebral ptosis and amaurosis (temporary or permanent). In
      this article, we present a complication that has been reported only rarely. Two
      patients developed transient loss of power of accommodation of the eye resulting
      in blurred vision after routine inferior alveolar nerve blocks on the ipsilateral
      side. Clear vision returned within 10-15 minutes after completion of the blocks.
      The possible explanation for this phenomenon is accidental injection into the
      neurovascular bundle of local anesthetic agents, which were carried via the blood
      to the orbital region. This resulted in paralysis of a branch of cranial nerve
      III, the short ciliary nerves that innervate the ciliary muscle, which controls
      accommodation.

PMID- 17187709
TI  - [Pelvic exenterations for gynaecological cancer--a 10 year institutional review].
AB  - Pelvic exenteration consists in a radical surgical procedure for patients with
      advanced cancer but limited to central pelvis. It is used for treatment of
      primary or recurrent tumours, or, more usually in treatment of recurrent cervical
      cancer. MATERIAL AND METHODS: Retrospective study of medical charts of patients
      underwent pelvic exenteration for gynaecological cancer between January 1995 and
      April 2005. RESULTS: Twenty-one pelvic exenterations were performed in this
      period. The mean age of the patients was 55.7 years. Indication for surgery
      included 14 (67%) recurrent cervical cancers; 2 uterine cancers (recurrent), 2
      vulvar cancer (one recurrent and one primary), 2 vagina carcinoma (one primary
      and one recurrent) and one patient with synchronous recto and uterine tumours.
      Exenteration was nine anterior, 3 posterior and 9 totals. The median length of
      hospitalization was 27 days. Most common postoperative complications were
      associated with urinary diversion. After surgery 19% of patients develops
      persistent lesion, 24% develops recurrent lesion with a middle free interval of
      12.4 months. After a median follow-up of 29 months, 10 patients (47%) are alive
      and free of disease. CONCLUSION: Pelvic exenteration can be offered as a surgical
      salvage therapy to patients with locally advanced gynaecological cancer.

PMID- 17187710
TI  - [The maximum systolic velocity increases in middle cerebral artery of normal
      fetus from 22nd to 38th week of gestation].
AB  - OBJECTIVE: To assess peak systolic velocity values in middle cerebral artery
      (PSMCA) of normal fetuses from 22nd to 38th week of gestation. MATERIAL AND
      METHODS: We made a prospective study of 33 healthy fetuses from 22nd to 38th to
      determine peak systolic velocity by Doppler velocimetry. Doppler ultrasound was
      performed by a single observer, always using the same apparatus. The Doppler
      tracing was obtained with a sample volume of 1 mm; placement was on the anterior
      middle cerebral artery, as close as possible to the skullcap. The insonation
      angle was kept below 20 degrees and the wall filter was adjusted to a frequency
      of 50-100 Hz. The PSMCA increases from 26.3 cm/s to 57.7 cm/s in middle cerebral
      artery from 22nd to 38th week of gestation (p < 0.05). There was a significant
      positive correlation between PSMCA and the gestational values (p < 0.001, r2 =
      60.5%). CONCLUSION: In normal fetuses, the PSMCA increases from 22nd to 38th week
      of gestation. The Doppler velocimetry values for normal fetuses could be compared
      with those obtained during fetal anemia.

PMID- 17187712
TI  - [First determination of the prevalence of celiac disease in a Portuguese
      population].
AB  - The prevalence of celiac disease is unknown in Portugal. In European countries
      the prevalence is between 1:200 and 1:400. The incidence obtained through
      diagnosed cases in the paediatric gastroenterology units in Portugal was 1:3648.
      To determine the best current celiac disease screening method and its prevalence
      in a portuguese population, 536 sera of teenagers with 14 years +/- 6 months from
      Braga town schools were tested as follows: a) total IgA, b) anti-tissue
      transglutaminase antibodies c) anti-endomysium antibodies (AEA). One female
      adolescent, with negative AEA and anti-transglutaminase antibodies had a
      diagnosed celiac disease; this patient was under appropriate diet. Eleven
      adolescents had positive anti-transglutaminase antibodies and 4 of these had also
      positive AEA. A jejunal biopsy was carried out on the latter adolescents. Three
      presented intestinal villous atrophy, 2 a flat mucosa and 1 a moderate atrophy.
      One female adolescent had a normal mucosa. The prevalence was 1:134, [confidence
      interval at 95%, 1:53-1:500]. CONCLUSIONS: Presently, total IgA with
      determination of anti-tissue transglutaminase antibodies is apparently the best
      screening method; it is less expensive test and, given the use of ELISA, less
      dependent on the observer. The celiac disease prevalence found in the present
      study falls within the range of prevalence recently found in other European
      populations, which implies that the celiac disease is under-diagnosed in
      Portugal.

PMID- 17187711
TI  - [Transvaginal ultrasound assessment of the cervix and digital examination before
      labor induction].
AB  - OBJECTIVE: To examine the relationship between sonographic measurement of
      cervical length and Bishop score with duration of labour induction. METHODS: A
      prospective, blinded, observational study was performed in 191 pregnant women
      undergoing labor induction. Ultrasound measurement of cervical length and
      determination of Bishop score were performed. Induction was based exclusively on
      the Bishop score according to Obstetric Unit protocol. The criteria for
      considering the cervix unripe were either Bishop score < 6 or a cervical length =
      26 mm. Duration of induction is defined like the induction-to-delivery interval.
      The main outcomes assessed were the duration of induction, the delivery within 24
      h of induction and type of delivery. RESULTS: The duration of induction was
      between 2 h 27 min and 61 h 30 min. We found an association between cervical
      length and Bishop score with duration of induction. The duration of induction was
      significantly increased in nulliparous (median 18 h 38 min vs. 9 h 18 min). There
      was no correlation of age or weight of pregnant women with the duration of
      induction. Comparison between Bishop score and cervical length in predicting
      delivery within the first 24 hours showed that the pregnant women with low Bishop
      score had a higher risk of deliver after 24 hours of induction (OR = 21.16), as
      the ones with cervical length longer than 26 mm (OR = 5.06). Analyzing the
      relation of these two parameters with type of delivery we realize that low Bishop
      score has a higher risk of cesarean section (OR = 2.67) and that there wasn't any
      relation between type of delivery and cervical length. DISCUSSION: In this study
      we verified a statistically significant relation between Bishop score, US
      cervical length and previous vaginal birth with induction duration. Pregnant
      woman's age and weight didn't have influence on the duration of induction. The
      study showed that both Bishop score and US cervical length are useful in
      predicting delivery within the first 24 hours. Bishop score was also related with
      type of delivery.

PMID- 17187713
TI  - [Pneumocystis jiroveci infection in immunocompetent patients with pulmonary
      disorders, in Portugal].
AB  - The use of molecular tools with a great capacity to detect and differentiate
      strains of Pneumocystis has resulted: in the identification of low numbers of P.
      jiroveci organisms in clinically silent, colonized, immunocompromised patients
      and in immunocompetent persons. Considering this information, the aim of this
      study was to determine the prevalence of P. jiroveci carriers (subclinical
      infections) in Portuguese patients with pulmonary disorders and in healthy
      individuals. A total of 45 pulmonary specimens were collected from 45
      immunocompetent adults with pulmonary disorders, and 37 oral washings from 37
      healthy adults, between March 2001 and February 2004. All samples were analysed
      by indirect immunofluorescence with monoclonal antibodies and by amplification of
      the LSU mtrRNA by nested PCR. The results obtained in this study indicate that:
      1) P. jiroveci is frequently detected (24.4%) in patients with pulmonary
      disorders in Portugal; 2) this population might play a role in circulation and
      transmission of P. jiroveci organisms in the community; 3) patients receiving
      corticosteroids are more likely to have detectable P. jiroveci in lungs (18%)
      than patients who are not receiving this immunosuppressor (12%); 4) P. jiroveci
      is infrequently detected in healthy adults. This may be due to very low numbers
      of latent organisms present in the lungs of healthy adults, difficulty in
      detecting few organisms, or due to the type of samples used. Screening of these
      individuals and notification of the results to their physician might be
      important: for further follow-up and whether or not prophylaxis or treatment
      should be prescribed; and for the clarification of the epidemiology of P.
      jiroveci asymptomatic infections.

PMID- 17187714
TI  - [The chorea of Zeze].
AB  - The authors analyse the correspondence between Eca de Queiroz, a well-known
      Portuguese writer, and his wife, in 1900, describing the neurological disease of
      their second son, Jose Maria d'Eca de Queiroz, know as Zeze. In those letters,
      the writer mentions chorea as his son diagnosis, explaining in detail its
      clinical picture. In addition, the writer reveals the medical thoughts of the
      time about the aetiology, treatment and natural history of Sydenham's Chorea.

PMID- 17187715
TI  - [General and family medicine: a gratifying choice].
AB  - The problematic discussion of speciality choice have been largely studied in
      other countries, where we can see the same setting of the announced crises of
      Primary Care and the so called decline of Family Medicine. In Portugal, many
      authors have shown an increasing concern in the way of getting more attention by
      the political policies/entities for the reduction of the number of family
      doctors. The decline of the interest of the medical students for Family Medicine
      is a complex and multifactorial problem that exists at international level, as in
      other generalist specialities, without technical procedures and technological
      investment. The importance of human values in medical education, by the new
      challenges that we have in the XXI century medicine, puts us the question about
      the students we are graduating today in our schools. The educational and health
      system reform, and the medical schools support, may influence the choices of
      medical graduates and motivate them for this speciality, developing a more real
      and more close medical care that responds to the interests and the needs of the
      population.

PMID- 17187716
TI  - [Anti-TNF alfa therapy in ankylosing spondylitis].
AB  - Ankylosing spondylitis (AS) is an inflammatory chronic disease that affects young
      males and in more than 90% of cases is associated with HLA B27 antigen.
      Therapeutic options for those patients with spondyloarthropathies have been
      limited during the last decades. Infliximab and etanercept are both approved for
      the treatment of patients with active disease that does not respond to
      conventional therapies. Anti-TNF therapy is very effective in AS, and eventually
      can be more effective than in rheumatoid arthritis. In 2003 Assessments in
      Ankylosing Spondylitis Group (ASAS) published international recommendations about
      the use of these agents in AS, which can be used as guidance in taking decisions
      and elaborating guidelines. To define their utilization it is necessary more
      studies about efficacy, toxicity and about ways of use.

PMID- 17187717
TI  - [Psychotropic drugs and sudden death].
AB  - Sudden death associated with psychotropic drugs is an issue in clinical practice
      which is currently debated worldwide in the literature. The objective of this
      work is to review recent literature on the issue (up to the end of 2004). The
      literature focuses mainly on the association between unexplained sudden death and
      antipsychotics and, to a lesser degree, tricyclic antidepressants; there are few
      references to other classes of psychotropic drugs. Over the last few decades
      various causal mechanisms have been proposed. However, recent literature refers
      mostly to sudden cardiac death induced by arrhythmias, and discusses, as a
      possible mechanism, the prolongation of the QTc interval due to the inhibition of
      potassium channels, leading to the risk of developing torsade de pointes which
      can result in sudden death. Although these cases of sudden death are rare,
      associated risk factors are also discussed because it is believed that a
      combination of several of these factors may increase the risk. We go on to
      consider recommendations to diminish the risk of sudden death. Finally, we review
      sudden death cases that have occurred in the last 5 years in the Acute
      Psychiatric Ward of S. Francisco Xavier Hospital (January 1999 to December 2004).

PMID- 17187718
TI  - [Psychiatric approach of liver transplant].
AB  - There is enough evidence about the importance psychiatric disorders (in the pre
      or post-operative period) have on the transplanted patient's clinical evolution
      and quality of life. In this review we describe, the main psychiatric items
      involved in the selection of candidates and accompaniment of transplanted
      patients. We concluded that psychiatric disorders are common in candidates in the
      pre-operative period. In this period the prevalence of depression is 33%, anxiety
      34%, alcohol dependence/abuse (in hepatic transplant candidates) 59%, delirium
      24% and alexithymia 28%. Psychiatric disorders are also common in candidates in
      the post-operative period. In this period the prevalence of depression is 30%,
      anxiety 26%, delirium 30%, PTSD 6.4% and psychosis 7.5%. The alcohol relapse
      after liver transplant occurs in about 29% of the transplanted patients. Patients
      with liver disease present metabolic specificities. In this article we list the
      psychiatric medications that are indicated in these kind of patients. Quality of
      life of the transplanted patient is determined by many factors such as
      neuropsychiatric status, psychiatric accompaniment, social support,
      planification, diet and compliance. Living donors must not be accepted when
      factors such as coercion and financial incentives or no understanding of the
      risks inherent in hepatic lobectomy are present.

PMID- 17187719
TI  - [Uterine inversion].
AB  - The uterine inversion is a rare but serious pathology of the delivery. We
      describe two cases of uterine inversion of secondary and quaternary degree; the
      first had a delay diagnosis and the second having a return after the manual
      replacement, finishing both on surgical resolution. The authors describe the
      causal factors, the diagnosis and the therapeutic of uterine inversion.

PMID- 17187720
TI  - [Unsuspected meningococcal disease].
AB  - INTRODUCTION: Meningococcal disease has a wide spectrum of clinical presentation.
      Occult bacteremia is not easily diagnosed and may have good prognostic. CLINIC
      REPORT: Three year-old African boy with fever, gonalgia and gait disorder with 24
      hours of evolution. Observation was unremarkable. He presented leukocytosis
      (27,300/mL) with neutrophilia (21,000/mL) and elevated reactive C protein (10.8
      mg/dl) with normal osteo-articular imagiologic exams. A blood culture was
      obtained and he was discharged with the probable diagnosis of hip synovitis. Two
      days later, he was asymptomatic without fever or blood infectious parameters
      although Neisseria meningitidis was identified in the blood culture. Ceftriaxone
      was given for seven days. Before starting this treatment a second blood culture
      was negative. There were no complications. DISCUSSION: Meningococcal disease may
      present with fever without toxic appearance--unsuspected meningococcal disease-
      causing difficulty in the diagnosis and delaying the treatment. Spontaneous
      resolution is rare and severe complications may occur.

PMID- 17187739
TI  - A study of hepatitis B vaccine efficacy 10 years after compulsory vaccination in
      Egypt.
AB  - This study aimed to determine the protective efficacy of hepatitis B vaccine
      against infection and chronic carriage in 720 children aged 10 years who were
      vaccinated in infancy. All children were tested for hepatitis B serologic markers
      including hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface
      antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) using 3rd
      generation ELISA technique. Only 37.9% of vaccinated children had protective anti
      HBs indicating its decay with time. Hepatitis B infection occurred in 6.8% of the
      vaccinated children and it induced a boosting effect on anti-HBs level. HBsAg was
      detected in 0.6% only of the vaccinated children. Thus we could conclude that up
      to 10 years, booster doses are unnecessary possibly due to protective anamnestic
      response to antigenic challenge. Further follow-up studies for longer duration
      than 10 years are needed especially during adolescence with the onset of sexual
      activity to monitor the vaccine efficacy in preventing chronic carriage and the
      possible necessity for booster doses.

PMID- 17187740
TI  - Seropositivity of toxoplasmosis in patients with schizophrenia.
AB  - Recent studies indicate that infectious agents may contribute to some cases of
      schizophrenia. In animals, infections with Toxoplasma gondii can alter behavior
      and neurotransmitter function. In humans, acute infection can produce psychotic
      symptoms similar to those displayed by persons with schizophrenia. In the present
      study, an enzyme immunoassay (EIA) was employed to measure the level of
      Toxoplasma IgG antibodies in serum samples from 75 patients of schizophrenia and
      85 matched controls. Percentage of positive sera for Toxoplasma IgG antibodies
      was significantly higher in schizophrenic cases than controls (80% vs. 52.9%
      respectively). Infection increased with age in both groups and no significant
      association was found with sex. No association was found with duration of illness
      or presence of family history of schizophrenia. Circumstantial evidence indicates
      that infection with Toxoplasma gondii may lead to some cases of schizophrenia.

PMID- 17187741
TI  - Health education program for mothers of children suffering from iron deficiency
      anemia in United Arab Emirates.
AB  - The present study was designed to assess knowledge, beliefs and practices of
      mothers regarding factors leading to iron deficiency anemia among children, to
      develop a health education (HE) program according to the needs of the target
      group, to determine the effect of the program in terms of changes in mothers'
      knowledge, practices and beliefs using Health Belief Model (HBM), and to
      determine the hemoglobin and hematocrite levels of the children of the target
      group before and after the program. The sample size was 200 anemic children aged
      6-24 months and their mothers, 100 of them were randomly assigned to face to face
      intervention program (experimental group) (I), the other 100 were the control
      group (II). Only 16% of mothers of group I and 18% of mothers of group II got
      satisfactory level of knowledge. After the conduction of HE program, the mothers'
      knowledge was significantly increased among group I, while almost there was no
      change of the knowledge's level among group II. Only 7% of mothers of group I and
      27% of those of group II had high perceived severity. Only 8% of mothers of group
      I and 14% of those of group II had low perceived barriers. After the program, 58%
      of mothers in group I got low perceived barriers. Only 28% of mothers of group I
      and 21% of those of group II had good dietary practice. After the program, 74% of
      mothers in group I showed good dietary practice. There were highly significant
      increases in the levels of hemoglobin and hematocrite of children of group I
      after the program, while the increases were not significant in group II.

PMID- 17187742
TI  - Health sector reform and equity: a study at a family health center affiliated to
      health insurance organization in Alexandria.
AB  - The 1990's witnessed a wave of reform in health systems of many countries. Health
      sector reform (HSR) initiatives aimed at improving health status, utilizers'
      satisfaction, as well as equity and accessibility of care. This study aims at
      exploring the question of whether there is a socioeconomically- based
      differential access to services provided by a family health center applying HSR.
      A total of 248 utilizers were randomly selected and interviewed. An access index
      comprised of eight elements was developed to measure access and its corollary
      equity. Results demonstrated that the majority belonged to the low middle socio
      economic class and one- quarter belonged to the low class. Approximately 9/10 of
      utilizers had high access to the services offered. Mean access index score for
      all utilizers was above the 90% mark. ANOVA analysis of mean access index
      according to socio-economic class revealed that there is no statistically
      significant disparity among various socio-economic classes regarding their access
      to care. However, it was demonstrated that higher classes had a higher opinion
      concerning the completeness of physical examination during the initial visit than
      lower classes. It was recommended to establish an appropriate policy framework to
      assure optimal standards of equity, preferably a 100% of high access as measured
      through the access index devised in this study.

PMID- 17187743
TI  - Safe injection practice among health care workers, Gharbiya, Egypt.
AB  - A cross-sectional study was conducted in 25 health care facilities in Gharbiya
      governorate to assess safe injection practices among health care workers (HCWs).
      Two questionnaires, one to collect information about administrative issues
      related to safe injection and the other to collect data about giving injections,
      exposure to needle stick injuries, hepatitis B vaccination status and safe
      injection training. Practices of injections were observed using a standardized
      checklist. The study revealed that there was lack of both national and local
      infection control policies and lack of most of the supplies needed for safe
      injection practices. Many safe practices were infrequent as proper needle
      manipulation before disposal (41%), safe needle disposal (47.5%), reuse of used
      syringe & needle (13.2%) and safe syringe disposal (0%). Exposure to needle stick
      injuries were common among the interviewed HCWs (66.2%) and hand washing was the
      common post exposure prophylaxis measure (63.4%). Only 11.3% of HCWs had full
      course hepatitis B vaccination. Infection control -including safe injections-
      training programs should be afforded to all HCWs.

PMID- 17187744
TI  - Environmental impacts of cooling system on Abou Qir Bay.
AB  - This study was conducted to evaluate the impacts of cooling water on cooling
      system of Abou Qir Power Plant and on the receiving Abou Qir Bay. Abou Qir Power
      Plant is a conventional steam electric power plant located in Alexandria
      Governorate, Egypt. Water and biota samples were collected monthly from cooling
      water and Abou Qir Bay over a year. Heavy metals, radionuclide, anions and total
      hydrocarbons were analyzed in the samples using Instrumental Neutron Activation
      Analysis (INAA), Gamma-ray Spectrometry (GS), Ion Selective Electrodes (ISE) and
      Gas Chromatography (GC). The results revealed that the characteristics of inlet
      cooling water had a tendency to be corrosive to the cooling system. The outlet
      cooling water complied with Environmental Law 4/1994 in all measured parameters
      except phosphate, ammonia and total petroleum hydrocarbons. On the other hand,
      samples from all sites had the lowest annual total count of algae in winter and
      highest count during summer. There are -ve correlations between algae and heavy
      metals, hydrocarbons, and radioactivity. Algae correlated highly significantly
      (p<0.01) with Pb, Cu, Ni, total petroleum hydrocarbons, dissolved petroleum
      hydrocarbon and uranium. Anabaena Sp. (blue green algae) and Euglina
      Sp.(flagellate) had highly significant (p<0.01) -ve correlation with heavy metals
      and natural radioactivity. The accumulation percentage of heavy metals by algae
      ranged from 22% to 37%, and the highest percent was for uranium and the lowest
      was for chromium. It is recommended to optimize the addition of polyphosphate
      inhibitor at inlet cooling water to inhibit corrosion in the cooling system and
      to avoid increase of Anabaena Sp. in the outlet, and to avoid enhancing algae
      growth that has a great tendency to accumulate heavy metals, and good
      housekeeping to avoid oil spills containing hydrocarbons from the power plant to
      sea water.

PMID- 17187746
TI  - Domestic violence among women attending out-patient clinics in Ain Shams
      University Hospitals, Cairo, Egypt.
AB  - Violence affects millions of women worldwide and it cuts across cultural and
      religious barriers, impeding the women's right to participate fully in the
      society. A descriptive cross sectional study was conducted to determine the
      prevalence of domestic violence among ever married females presenting to out
      patient clinics in Ain Shams university hospitals and to identify factors
      affecting it. Out of a total number of 509 women, 89.8% had experienced one or
      more episodes of violent behavior by their husbands of which 56%, 88.4% and 47.9%
      suffered physical, control and threat violence. Both univariate and multivariate
      analysis was done. The most common form of violence among the study group was
      husband's shouting followed by being kept short of money. About 34.2% had been
      beaten by their husbands and 17.1% were forced to do sex. Using multiple logistic
      regression it was found that smoking husband and economic problems were
      independent significant factors associated with all forms of violence. Suffering
      violence was significantly associated with different forms of health complaints
      and only 9.1% had been asked by their doctors on domestic violence exposure. This
      proposes the importance of effective screening, diagnosis and management of
      domestic violence victims.

PMID- 17187745
TI  - A comparative study on the medical waste disposal in some hospitals in
      Alexandria.
AB  - Though healthcare services aim to reduce the health problems and prevent the
      potential risks to the health of the community. These services create wastes
      which are considered as hazardous materials due to the higher potential of
      infection and injury possessed by these wastes than any other type of waste.
      Healthcare waste management is an integral part of healthcare services, and can
      create harm through inadequate waste management; thus reducing the overall
      benefits provided by healthcare centers. In the current study, a survey for
      medical waste disposal was performed in order to examine the current status of
      medical waste disposal in some hospitals in Alexandria and to properly assess
      management of this type of hazardous waste. A questionnaire was designed for
      hospitals to assess the quantity of medical waste, collection, sorting, storage,
      transportation and way of final disposal. From the total waste generated by
      healthcare activities, almost 80% are waste similar to domestic waste. The
      remaining approximate of 20% is considered as hazardous waste. As Alexandria has
      about 3911 healthcare facilities providing medical services for people, a huge
      amount of medical waste are generated daily with about 208 tons generated per
      month. The results revealed that the most common problems associated with
      healthcare wastes are the absence of waste management, lack of awareness about
      their health hazards, insufficient financial and human resources for proper
      management, and poor control of waste disposal. The current situation of medical
      waste disposal in Alexandria is depending on incinerators. Some of these
      incinerators are not working anymore. Incinerations as a system is not accepted
      at the time being in most developed countries due to the risks associated with it
      and suitable substitution management system for medical waste disposal is now
      taking its place.

PMID- 17187747
TI  - TT virus among blood donors in Alexandria.
AB  - TTV is a non enveloped, single-stranded, circular- DNA virus that has been
      assigned to the Family Circiniviridae. The primary mode of TTV transmission was
      proposed to be transfusion (and hence its name). Little is known about the
      clinical significance and the natural history of TTV infection. Hence,
      responsibility of the virus for specific liver disease is still debated. In our
      study, we tested ninety five blood donors attending Kom EL-Decka regional blood
      bank in Alexandria for the presence of TTV DNA in their sera by PCR technique.
      The same samples were tested for ALT and AST levels by colorimetric technique and
      for HBsAg and anti-HCV by the ELISA technique. Out of the 95 blood donors, 46
      (48.4%) had TTV DNA in their sera. None of the 95 blood donors included in this
      study was positive for HBsAg, while 22 (23.2%) were anti-HCV positive. Out of the
      22 anti-HCV positive blood donors, 13 (59.1%) were TTV DNA positive, while out of
      the 73 anti-HCV negative blood donors, 33 (45.2%) had TTV DNA in their sera.
      There was no statistically significant difference between the prevalence of TTV
      DNA and anti-HCV in blood donors. No biochemical evidence of liver disease
      potentially linked to the TTV infection was observed in our blood donors who were
      TTV DNA positive. Furthermore, the occurrence of elevated serum AST and ALT was
      most often linked to HCV rather than TTV.

PMID- 17187748
TI  - Early detection of protein energy malnutrition in Sharkia Governorate.
AB  - The objective of this cross-sectional study was to assess the nutritional status
      of children, aged 6 to 36 months, in Sharkia Governorate aiming for early
      detection of malnourished cases. METHODS: the present study was carried out on
      1000 children aged 6 to 36 months, selected by a multistage random sample from 6
      villages in two districts in Sharkia Governorate. Data were gathered by an
      interview questionnaire to the child's mother or care giver at their homes.
      Anthropometric measurements as height, weight, mid-arm, head circumference and
      skin fold thickness were assessed. Body mass index was calculated. Dietary
      evaluation was done by a 24 hours recall for amounts and frequencies of food and
      was transferred to their recommended daily allowance (RDA). The studied children
      were classified into three groups according to their weight for age percentiles,
      underweight children, borderline malnourished children and normal weight
      children. Serum hemoglobin, pre-albumin and albumin were assessed for a randomly
      selected number of the studied group. RESULTS: the study showed that all
      anthropometric measurements were lower than normal in underweight and borderline
      subjects. The prevalence rates of wasting, stunting and underweight were 15%,
      24.4% and 15.4% in the studied infants in Sharkia Governorate, respectively. The
      study revealed that nutrient intake of the study subjects was lower than the RDA
      for the energy intake from carbohydrates, vitamin D, and iron, while it was
      higher than the RDA for the energy intake from lipids and vitamin A and equal to
      the lower level of the normal range of RDA for the energy intake from proteins.
      Most of the protein intake was of plant origin. Caloric intake was less than RDA
      in underweight and border line children, but more than RDA in normal children
      (86%, 90% and 102%). The ratios of caloric intake to the required calories
      according to weight were 90%, 98% and 108% in the three groups respectively.
      Chronic cough and chronic and recurrent diarrhea were more complained by
      underweight and borderline children. Underweight children were more infested with
      oxyurius and entamoeba histolitica than the other 2 groups. Serum hemoglobin,
      albumin and plasma pre-albumin levels were within normal range with significantly
      lower values in underweight and borderline infants compared to normal children.
      By multiple linear regression analysis, the most important factors affecting BMI
      were carbohydrate, lipid and caloric intake, serum albumin, plasma pre-albumin,
      vitamin A and D intake and protein intake. CONCLUSION: There is a high prevalence
      of wasting ,stunting and underweight among infants and children of the studied
      sample in Sharkia governorate explained by the low socioeconomic status,
      unbalanced diet. Early changes of protein energy malnutrition were detected, in
      spite of the fact that serum hemoglobin, albumin and plasma pre-albumin levels
      were within normal range, they were significantly lower in underweight and
      borderline infants compared to normal children.

PMID- 17187749
TI  - The profile of high-risk pregnancy in El-Mansoura city.
AB  - Proper screening techniques should be used for all pregnant women attending
      antenatal clinics to pick up the factors that qualify the pregnant women for a
      risky pregnancy. High-risk pregnancy identification is a challenging work. This
      study aimed to describe the profile of high-risk pregnancy in El-Mansoura city.
      The study was conducted on 750 pregnant women attending antenatal clinics in
      three hospitals in El-Mansoura city, where 250 women were chosen from each
      setting. A modified version of Morrison and Olsen (1979) high risk scoring
      inventory tool was used to collect the socioeconomic, biological, medical,
      reproductive and current pregnancy risk factors in the study sample. It also
      assessed the risk level whether low, moderate or high. The results revealed that
      among all women, 63.8% of the sample were at a high-risk, while 25.0 % of them
      were at a moderate-risk and only 11.2% were at low-risk. About 70.0% of the high
      risk pregnant women were in their third trimester followed by 23.0% in the second
      trimester and only 7.1% were in the first trimester. About 5.9% of the women were
      at a high-risk because of polluted housing condition, 1.9% because of heart
      diseases Class capital I, Ukrainian or II, 5.2% because of diabetes mellitus,
      4.2% because of hypertension and 14.9% because of previous cesarean section. On
      the other hand 14.8% women were at moderate risk because of their illiteracy,
      29.2% of them for being short, 14.7%, 10.6% of them because of being teenagers or
      over 35 years of age, respectively, 12.6% of because they had a history of
      gestational diabetes and 32.8%of them because of anemia, 23.2% because urinary
      tract infection, 16.9% because of albuminuria, and 12.0% because of glucoseuria.
      Finally identifying the profile of high -risk pregnancy women is mandatory.

PMID- 17187750
TI  - Crossmodal change blindness between vision and touch.
AB  - Change blindness is the name given to people's inability to detect changes
      introduced between two consecutively-presented scenes when they are separated by
      a distractor that masks the transients that are typically associated with change.
      Change blindness has been reported within vision, audition, and touch, but has
      never before been investigated when successive patterns are presented to
      different sensory modalities. In the study reported here, we investigated change
      detection performance when the two to-be-compared stimulus patterns were
      presented in the same sensory modality (i.e., both visual or both tactile) and
      when one stimulus pattern was tactile while the other was presented visually or
      vice versa. The two to-be-compared patterns were presented consecutively,
      separated by an empty interval, or else separated by a masked interval. In the
      latter case, the masked interval could either be tactile or visual. The first
      experiment investigated visual-tactile and tactile-visual change detection
      performance. The results showed that in the absence of masking, participants
      detected changes in position accurately, despite the fact that the two to-be
      compared displays were presented in different sensory modalities. Furthermore,
      when a mask was presented between the two to-be-compared displays, crossmodal
      change blindness was elicited no matter whether the mask was visual or tactile.
      The results of two further experiments showed that performance was better overall
      in the unimodal (visual or tactile) conditions than in the crossmodal conditions.
      These results suggest that certain of the processes underlying change blindness
      are multisensory in nature. We discuss these findings in relation to recent
      claims regarding the crossmodal nature of spatial attention.

PMID- 17187751
TI  - Transchip: single-molecule detection of transcriptional elongation complexes.
AB  - A new single-molecule system, Transchip, was developed for analysis of
      transcription products at their genomic origins. The bacteriophage T7 RNA
      polymerase and its promoters were used in a model system, and resultant RNAs were
      imaged and detected at their positions along single template DNA molecules. The
      Transchip system has drawn from critical aspects of Optical Mapping, a single
      molecule system that enables the construction of high-resolution ordered
      restriction maps of whole genomes from single DNA molecules. Through statistical
      analysis of hundreds of single-molecule template/transcript complexes, Transchip
      enables analysis of the locations and strength of promoters, the direction and
      processivity of transcription reactions, and the termination of transcription.
      These novel results suggest that the new system may serve as a high-throughput
      platform to investigate transcriptional events on a large genome-wide scale.

PMID- 17187752
TI  - Protein aggregation and degradation during iodine labeling and its consequences
      for protein adsorption to biomaterials.
AB  - Protein adsorption on modified and unmodified polymer surfaces investigated
      through radiolabeling experiments showed a tendency for higher than expected
      albumin and immunoglobulin G (IgG) adsorption. Possible enhanced protein
      aggregation and degradation caused by the iodine labeling method used were
      analyzed through chromatography and spectroscopy techniques. Results show that
      the iodine labeling method using chloramine-T (CAT) as an oxidizing agent can
      cause both enhanced aggregation and fragmentation of proteins. Albumin shows an
      enhanced tendency to aggregate after iodine labeling using the CAT method, and
      higher amounts of fragmentation are observed for CAT-labeled IgG molecules
      relative to unlabeled IgG molecules as well as to IgG molecules labeled using the
      Iodo-Gen method. These results show that the widely applied method of
      radioisotope labeling for quantitative assessment of protein adsorption should be
      used with caution and preferably should be validated by a label-free methodology
      for each combination of radiolabel and protein. The results obtained in this
      study can be used to optimize investigation of protein adsorption on surfaces of
      materials for biomedical devices.

PMID- 17187753
TI  - Discovery and development of a type II collagen neoepitope (TIINE) biomarker for
      matrix metalloproteinase activity: from in vitro to in vivo.
AB  - Destruction of cartilage by matrix metalloproteinases (MMPs) plays a significant
      role in the pathology of osteoarthritis (OA). A translatable biomarker of MMP
      activity would enable development of MMP inhibitors for the treatment of OA and
      potentially the improved diagnosis of OA. A directed approach to identifying
      specific MMP cleavage products as potential biomarkers has been undertaken.
      Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify
      peptides generated by MMP-driven degradation of human articular cartilage (HAC)
      in vivo. It was shown that a 45-mer peptide fragment of collagen type II with
      five hydroxyprolines (OH) can be selectively produced by the activity of
      collagenase, an enzyme purported to be involved in the pathology of OA. This 45
      mer is the most abundant neoepitope peptide found in biological fluids such as
      urine and synovial fluid. An immunoaffinity LC-MS/MS assay has been developed to
      quantify collagen type II neoepitope peptides as biomarkers of collagenase
      modulation. The lower limit of quantification for this assay was established to
      be 0.035 nM. The assay was used to measure the levels of collagen type II
      peptides in the urine of both clinical (healthy human subjects) and preclinical
      species. The urinary levels of the most abundant peptides are reported for rat,
      rabbit, guinea pig, dog, and healthy human adult subjects. The utility of this
      peptide to monitor collagenase activity in vivo has been demonstrated through its
      detailed characterization in HAC explants as well as in the urine of human and
      other preclinical species.

PMID- 17187754
TI  - Artificial model of photosynthetic oxygen evolving complex: catalytic O2
      production from water by di-mu-oxo manganese dimers supported by clay compounds.
AB  - Adsorption of [(OH(2))(terpy)Mn(mu-O)(2)Mn(terpy)(OH(2))](3+) (terpy=2,2':6',2"
      terpyridine) (1) onto montmorillonite K10 (MK10) yielded catalytic dioxygen
      (O(2)) evolution from water using a Ce(IV) oxidant. The Mn K-edge X-ray
      absorption near edge structure (XANES) of the 1/MK10 hybrid suggested that the
      oxidation state of the di-mu-oxo Mn(2) core could be Mn(III)-Mn(IV). However the
      pre-edge peak in the XANES spectrum of 1 adsorbed on MK10 is different from the
      neat 1 powder. The kinetic analysis of O(2) evolution showed that the catalysis
      requires cooperation of two equivalents of 1 adsorbed on MK10. The reaction of
      the [(bpy)(2)Mn(mu-O)(2)Mn(bpy)(2)](3+) (bpy=2,2'-bipyridine) (2)/MK10 hybrid
      with a Ce(IV) oxidant evolved O(2). However, the turnover number value was less
      than unity for 2/MK10, showing that 2 adsorbed on MK10 does not work as a
      catalyst. The terminal water ligands could be an important for the catalysis by
      adsorbed 1. The mechanism of O(2) production by photosynthetic oxygen evolving
      complex is discussed based on catalytic O(2) evolution by 1 adsorbed on MK10.

PMID- 17187756
TI  - Snail is required for transforming growth factor-beta-induced epithelial
      mesenchymal transition by activating PI3 kinase/Akt signal pathway.
AB  - Lens epithelial cells undergo epithelial-mesenchymal transition (EMT) after
      injury as in cataract extraction, leading to fibrosis of the lens capsule. We
      have previously shown that EMT of primary lens epithelial cells in vitro depends
      on TGF-beta expression and more specifically, on signaling via Smad3. In this
      report, we suggest phosphatidylinositol 3-OH kinase (PI3K)/Akt signaling is also
      necessary for TGF-beta-induced EMT in lens epithelial cells by showing that
      LY294002, an inhibitor of the p110 catalytic subunit of PI3K, blocked the
      expression of alpha-smooth muscle actin (alpha-SMA) and morphological changes. We
      also identify Snail as an effector of TGF-beta-induced EMT. Snail has been shown
      to be a mediator of EMT during metastasis of cancer. We show that Snail is an
      immediate-early response gene for TGF-beta and the proximal Snail promoter is
      activated by TGF-beta through the action of Smad2, 3, and 4. We show that
      antisense inhibition of Snail expression blocks TGF-beta-induced EMT and
      furthermore Akt activation. All of these findings suggest that Snail participates
      in TGF-beta-induced EMT by acting upstream of Akt activation.

PMID- 17187757
TI  - Transcription factors involved in the expression of SLC28 genes in human liver
      parenchymal cells.
AB  - Human nucleoside transporters are encoded by SLC28 (hCNTs) and SLC29 (hENTs)
      genes. These proteins mediate the uptake of anticancer and some antiviral drugs
      and are also suitable candidates to facilitate nucleoside-derived drug uptake
      into hepatocytes for detoxification. Despite the putative relevance of these
      genes in liver physiology, the human SLC28 and SLC29 expression pattern is not
      known and suitable cell models are not available. These issues have been
      addressed by examining NT expression in human liver and primary cultures of human
      hepatocytes. Moreover, the effect of specific liver enriched transcription
      factors (LETFs) in hCNTs expression has been analyzed. Human hepatocytes express
      hCNT1, hCNT2, hENT1, and hENT2. Loss of the hepatic phenotype in primary culture
      is associated with a decrease in hCNT1 and hCNT2 mRNA levels. Selected LETFs are
      involved in the regulation of SLC28 genes in an isoform-specific manner.
      HNF4alpha is a major determinant of SLC28A1 expression, whereas C/EBPalpha and
      HNF3gamma modulate SLC28A2 gene expression.

PMID- 17187755
TI  - Hydrogen-bond formation of the residue in H-loop of the nucleotide binding domain
      2 with the ATP in this site and/or other residues of multidrug resistance protein
      MRP1 plays a crucial role during ATP-dependent solute transport.
AB  - MRP1 couples ATP binding/hydrolysis to solute transport. We have shown that ATP
      binding to nucleotide-binding-domain 1 (NBD1) plays a regulatory role whereas ATP
      hydrolysis at NBD2 plays a crucial role in ATP-dependent solute transport.
      However, how ATP is hydrolyzed at NBD2 is not well elucidated. To partially
      address this question, we have mutated the histidine residue in H-loop of MRP1 to
      either a residue that prevents the formation of hydrogen-bonds with ATP and other
      residues in MRP1 or a residue that may potentially form these hydrogen-bonds.
      Interestingly, substitution of H827 in NBD1 with residues that prevented
      formation of these hydrogen-bonds had no effect on the ATP-dependent solute
      transport whereas corresponding mutations in NBD2 almost abolished the ATP
      dependent solute transport completely. In contrast, substitutions of H1486 in H
      loop of NBD2 with residues that might potentially form these hydrogen-bonds
      exerted either full function or partial function, implying that hydrogen-bond
      formation between the residue at 1486 and the gamma-phosphate of the bound ATP
      and/or other residues, such as putative catalytic base E1455, together with S769,
      G771, T1329 and K1333, etc., holds all the components necessary for ATP
      binding/hydrolysis firmly so that the activated water molecule can efficiently
      hydrolyze the bound ATP at NBD2.

PMID- 17187758
TI  - Aberrant DNA methylation of the 5' upstream region of Tslc1 gene in hamster
      pancreatic tumors.
AB  - To determine if the Tslc1 gene is involved in pancreatic carcinogenesis, the
      expression level of Tslc1 and the DNA methylation status of its 5' upstream
      region were investigated in pancreatic duct adenocarcinomas (PDAs) induced in
      hamsters by N-nitrosobis(2-oxopropyl)amine (BOP). Female Syrian golden hamsters
      received 70 mg/kg of BOP followed by repeated exposure to an augmentation
      pressure regimen consisting of a choline-deficient diet combined with ethionine
      methionione-BOP injection. Total RNA was extracted from 11 PDAs and the level of
      Tslc1 expression was measured in each by real-time quantitative reverse
      transcription (RT)-polymerase chain reaction (PCR). The expression level of Tslc1
      was significantly reduced in PDAs (p < 0.05) compared with normal pancreatic
      tissues. In order to assess the DNA methylation status of the 5' upstream region
      of Tslc1, bisulfite sequencing was performed. Although this region was
      unmethylated in normal pancreatic tissue, it was highly methylated in four PDAs,
      correlating with reduced Tslc1 expression. These results suggest that a reduction
      in the expression of Tslc1 due to aberrant DNA methylation might be involved in
      the development of PDAs induced in hamsters by BOP.

PMID- 17187759
TI  - Temperature-sensitive defects of the GSP1gene, yeast Ran homologue, activate the
      Tel1-dependent pathway.
AB  - RanGTPase is involved in many cellular processes. It functions in nuclear
      cytosolic transport and centrosome formation. Ran also localizes to chromatin as
      RCC1 does, its guanine nucleotide exchange factor, but Ran's function on
      chromatin is not known. We found that gsp1, a temperature-sensitive mutant of
      GSP1, a Saccharomyces cerevisiae Ran homologue, suppressed the hydroxyurea (HU)
      and ultra violet (UV) sensitivities of the mec1 mutant. In UV-irradiated mec1
      gsp1 cells, Rad53 was phosphorylated despite the lack of Mec1. This suppression
      depended on the TEL1 gene, given that the triple mutant, mec1 gsp1 tel1, was
      unable to grow. The gsp1 mutations also suppressed the HU sensitivity of the rad9
      mutant in a Tel1-dependent manner, but not the HU sensitivity of the rad53
      mutant. These results indicated that Rad53 was activated by the Tel1 pathway in
      mec1 gsp1 cells, suggesting that Gsp1 helps regulate the role switching the ATM
      family kinases Mec1 and Tel1.

PMID- 17187760
TI  - Glucose regulation of beta-defensin-1 mRNA in human renal cells.
AB  - We previously showed that beta-defensin-1 (BD-1), an anti-microbial peptide, is
      up-regulated during progressive hyperglycemia in the kidneys of the GK rat [R.A.
      Page, C.A. Morris, J.D. Williams, C.J. von Ruhland, A.N. Malik, Isolation of
      diabetes-associated kidney genes using differential display, Biochem. Biophys.
      Res. Commun. 232 (1997) 49-53, R.A. Page, A.N. Malik, Elevated levels of beta
      defensin-1 mRNA in diabetic kidneys of GK rats, Biochem. Biophys. Res. Commun.
      310 (2003) 513-521]. In this paper, we show that human beta-defensin-1 (hBD-1)
      mRNA is directly up-regulated by glucose in cultured human renal cells. hBD-1
      mRNA levels increased by approximately 7-fold and approximately 4-fold in human
      embryonic kidney (HEK) cells and human mesangial cells (HMC) grown in 25mM
      glucose for four days, as determined by quantitative real-time PCR.
      Immunofluorescence showed that the hBD1 protein is located in the cytoplasm of
      HEK cells and transfected HMCs. The highest levels of hBD-1 mRNA were found in
      the kidney compared with 21 other human tissues. The increased expression of hBD
      1 mRNA in cultured HMCs in high glucose suggests a role for hBD-1 in the
      molecular pathways induced during hyperglycemia.

PMID- 17187761
TI  - EOS1, whose deletion confers sensitivity to oxidative stress, is involved in N
      glycosylation in Saccharomyces cerevisiae.
AB  - The deletion strain of Saccharomyces cerevisiae YNL080c (designed as EOS1) was
      identified as a strain sensitive to high-sucrose stress in our previous report
      [A. Ando, F. Tanaka, Y. Murata, H. Takagi, J. Shima, Identification and
      classification of genes required for tolerance to high sucrose stress revealed by
      genome-wide screening of Saccharomyces cerevisiae, FEMS Yeast Res. 6 (2006) 249
      267]. Delta eos1 showed higher sensitivity to oxidative stress than to high
      sucrose stress. Immunofluorescence microscopic and cellular fractionation
      analyses suggested that Eos1 localizes in the endoplasmic reticulum membrane. We
      found that the deletion of EOS1 enhances tunicamycin tolerance and that in Delta
      eos1 the transcription level of KAR2, which is the ER stress-inducible gene, was
      much lower than that in the wild-type strain (BY4741) when exposed to
      tunicamycin. The inhibition of the N-glycosylation of carboxypeptidase Y and
      invertase activity caused by the addition of tunicamycin was depressed in Delta
      eos1, suggesting that EOS1 may be involved in N-glycosylation of the cellular
      proteins.

PMID- 17187762
TI  - Calcium-induced synergistic inhibition of a translational factor eEF2 in nerve
      growth cones.
AB  - Local protein synthesis in nerve growth cones has been suggested, but how it is
      controlled remains largely unknown. We found eukaryotic elongation factor-2
      (eEF2), a key component of mRNA translation, in growth cones by
      immunocytochemistry. While phosphorylated eEF2 was weakly distributed in
      advancing growth cones, eEF2 phosphorylation was increased by high potassium
      evoked calcium influx. In the growth cone, calcium elevation increased eEF2
      kinase (EF2K), a calcim-calmodulin-dependent enzyme. Calcium also decreased the
      level of phosphorylated p70-S6 kinase (S6K), a kinase known to inhibit EF2K.
      Moreover, calcium elevation decreased total eEF2 in growth cones. Since
      phosphorylated eEF2 inhibits mRNA translation, calcium elevation appears to
      inhibit mRNA translation in growth cones by a synergistic mechanism involving
      regulation of EF2K, S6K, and eEF2 itself. Time-lapse imaging showed that calcium
      elevation induced growth arrest of neurites. The inhibitory effect on mRNA
      translation may thus be involved in the regulation of neurite outgrowth.

PMID- 17187763
TI  - Analysis of PGC-1alpha variants Gly482Ser and Thr612Met concerning their
      PPARgamma2-coactivation function.
AB  - Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)
      is a cofactor involved in adaptive thermogenesis, fatty acid oxidation, and
      gluconeogenesis. Dysfunctions of this protein are likely to contribute to the
      development of obesity and the metabolic syndrome. This is in part but not
      definitely confirmed by results of population studies. The aim of this study was
      to investigate if common genetic variants rs8192678 (Gly482Ser) and rs3736265
      (Thr612Met) in the PGC-1alpha gene lead to a functional consequence in cofactor
      activity using peroxisome proliferator-activated receptor-gamma 2 (PPARgamma2) as
      interacting transcription factor. Reporter gene assays in HepG2 cells with
      wildtype and mutant proteins of both PGC1alpha and PPARgamma2 (Pro12Ala,
      rs1801282) using the acyl-CoA-binding protein (ACBP) promoter showed no
      difference in coactivator activity. This is the first study implicating that the
      Gly482Ser and Thr612Met polymorphisms in PGC-1alpha and Pro12Ala polymorphism in
      PPARgamma2 do not affect the functional integrity of these proteins.

PMID- 17187764
TI  - Influence of ultraviolet-C on the compositions of cell-wall polysaccharides and
      carbohydrase activities of Silene vulgaris callus.
AB  - UV-C irradiation (254 nm) was found to enhance the secretion of some cell-wall
      degrading enzymes, especially the following carbohydrases: beta-galactosidase,
      alpha-L-arabinofuranosidase, polygalacturonase, pectinesterase, cellulase,
      xylanase, and beta-xylosidase, in the campion callus, contributing thereby to an
      alteration in the polysaccharide structure. The relative amounts of the galactose
      and arabinose residues in pectin (silenan) and of arabinose in arabinogalactan of
      calli irradiated during the exponential phase were shown to decrease during the
      stationary phase. A decrease in the degree of SV methylesterification was found
      for the irradiated callus. These alterations were found to persist over a long
      period of culturing time. Decreasing the relative amounts of the arabinose
      residues in arabinogalactan and pectin and the galactose residues in silenan
      corresponded to increasing activity of alpha-L-arabinofuranosidase and beta
      galactosidase, respectively, due to treatment with UV-C. UV-C irradiation may be
      used as a tool for modifying the structural features of the cell-wall
      polysaccharides, such as the relative amounts of galactose and arabinose residues
      in the side chains of polysaccharides, with the purpose of obtaining
      physiologically active polysaccharides with the desired properties and structural
      features.

PMID- 17187766
TI  - Role of bone morphogenetic proteins in cardiac differentiation.
AB  - Bone morphogenetic proteins (BMP) are involved in the regulation of a plethora of
      processes underlying cardiovascular development. This review summarizes the
      effects of BMP and the signaling pathways that regulate the differentiation of
      cardiomyocytes from mesoderm in the heart-forming region and at the distal
      borders of the heart tube from the second heart field. Subsequently, the role of
      BMPs in the formation of the ventricular chambers and septovalvulogenesis in the
      atrioventricular canal and outflow tract is described. Finally, the effects of
      BMPs in stem cell biology and cardiac regeneration are discussed.

PMID- 17187765
TI  - Short- and long-term effects of cytochalasin D, paclitaxel and rapamycin on wall
      thickening in experimental porcine vein grafts.
AB  - OBJECTIVES: Neointima formation and wall thickening caused by smooth muscle cell
      proliferation compromise long-term patency of human aorto-coronary vein-grafts.
      We investigated short- and long-term effects of anti-proliferative
      pharmacological agents on experimental pig vein-grafts with similar dimensions
      and kinetics to human coronary grafts. METHODS AND RESULTS: Saphenous veins were
      treated for 1 h ex vivo with vehicle or concentrations of cytochalasin D,
      paclitaxel or rapamycin found to be anti-proliferative in preliminary studies.
      Vehicle and treated veins were implanted contralaterally, end-to-end into the
      carotid arteries of pigs. Cytochalasin D 2.5 mug/ml non-significantly reduced
      neointima formation in 4-week vein-grafts (mean+/-standard error, 2.5+/-0.6 vs.
      3.3+/-0.6 mm2, n = 10, p = NS), whilst paclitaxel 10 microM produced significant
      inhibition (1.7+/-0.2 vs. 3.0+/-0.3 mm2, n = 8, p < 0.01) as did rapamycin 0.1
      mg/ml (0.6+/-0.3 vs. 1.7+/-0.5 mm(2), n = 8, p < 0.02). Similar effects were
      found on total wall cross-sectional area but medial area was unaffected. PCNA
      staining of 1-week vein grafts confirmed in vivo anti-proliferative effects of
      paclitaxel (21+/-2 vs. 36+/-3%, n = 5, p < 0.01) and rapamycin (32+/-1 vs. 57+/
      6%, n = 6, p < 0.005); neither agent stimulated loss of endothelium at these
      concentrations. Neointima and total wall area increased significantly between 4-
      and 12-weeks in all vein-grafts such that there was no longer a significant
      effect on neointima formation of either paclitaxel (7.5+/-1.3 vs. 8.9+/-1.9 mm2
      in control, n = 5, p = NS) or rapamycin (6.0+/-0.9 vs. 7.9+/-1.1 mm2 in control,
      n = 9, p = NS) or on total wall area in 12-week grafts. CONCLUSIONS: Pre
      treatment of saphenous vein with anti-proliferative agents paclitaxel or
      rapamycin reduced neointima and total wall area after 4 weeks but continued
      growth abolished differences by 12 weeks. These results may help to understand
      the failure of clinical studies using anti-proliferative treatments in vein
      grafts.

PMID- 17187768
TI  - Modifying dipalmitoylphosphatidylcholine monolayers by n-hexadecanol and
      dipalmitoylglycerol.
AB  - The monolayer structure of pure dipalmitoylphosphatidylcholine (DPPC) and
      equimolar mixtures of DPPC/n-hexadecanol (C(16)OH) and DPPC/dipalmitoylglycerol
      (DPG) are studied by the film balance technique and grazing incidence X-ray
      diffraction measurements. At 20 degrees C, the binary systems exhibit complete
      miscibility. In contrast to pure DPPC monolayers, a condensing effect is observed
      in the presence of both non-phospholipid additives; but the phase transition
      behavior differs. The tilt angle of the hydrocarbon chains in the DPPC/C(16)OH
      mixture is significantly smaller than in pure DPPC monolayers. The tilt of the
      chains is even further reduced in the mixed monolayer of DPPC/DPG. A comparison
      of the three systems reveals distinct structural features such as phase state,
      chain tilt, and molecular area over a wide range of surface pressures. Therefore,
      these monolayers provide a highly suitable model to investigate the influence of
      structural parameters on biological processes occurring at the membrane surface,
      e.g. enzymatic reactions and adsorption events.

PMID- 17187767
TI  - Cadmium inhibits delta-aminolevulinate dehydratase from rat lung in vitro:
      interaction with chelating and antioxidant agents.
AB  - The effect of cadmium (Cd(2+)) on delta-aminolevulinate dehydratase (delta-ALA-D)
      activity from rat lung in vitro was investigated. delta-ALA-D activity, a
      parameter for metal intoxication, has been reported as a target of Cd(2+) in
      different tissues. The protective effect of monotherapies with dithiol chelating
      (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic
      acid (DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)(2),
      and N-acetylcysteine (NAC)) was evaluated. The effect of a combined therapy
      (dithiol chelatingxantioxidant agent) was also studied. Zinc chloride (ZnCl(2))
      and dithiothreitol (DTT) were used to investigate the mechanisms involved in
      cadmium, chelating and antioxidant effects on delta-ALA-D activity. Cadmium
      inhibited rat lung delta-ALA-D activity at low concentrations. DTT (3mM), but not
      ZnCl(2) (100microM), protected the inhibition of enzyme activity caused by
      Cd(2+). Chelating agents were not effective in restoring the enzyme activity.
      DMPS and DMSA presented inhibitory effect on enzyme activity. DTT restored the
      inhibition caused by both chelating agents, but ZnCl(2) restored only the
      inhibitory effect induced by DMSA. These compounds caused a marked potentiation
      of delta-ALA-D inhibition induced by Cd(2+). ZnCl(2) did not restore inhibition
      of enzyme activity caused by Cd(2+) plus chelating agents. Conversely, DTT
      restored the inhibition induced by Cd(2+)/DMSA, but not by Cd(2+)/DMPS.
      Antioxidants were not effective in ameliorating delta-ALA-D inhibition induced by
      Cd(2+), whereas ascorbic acid potentiated the enzyme inhibition induced by this
      metal. A combined effect of Cd(2+)xDMPSx(PhSe)(2) and Cd(2+)xDMPSxNAC was
      observed. There was no combined effect of Cd(2+)xchelatorxantioxidants when DMSA
      was used. This study demonstrated that Cd(2+)inhibited delta-ALA-D activity and
      chelating and antioxidant agents, alone or combined, did not restore the enzyme
      activity. In contrast, these compounds potentiated the inhibition induced by
      Cd(2+) in rat lung.

PMID- 17187769
TI  - Unnecessary coronary angiography due to false positive troponin I results in a 51
      year-old man.

PMID- 17187770
TI  - Category essence or essentially pragmatic? Creator's intention in naming and
      what's really what.
AB  - Daily experience is filled with objects that have been created by humans to serve
      specific purposes. For such objects, the very act of creation may be a key
      element of how people understand them. But exactly how does creator's intention
      matter? We evaluated its contribution to two forms of categorization: the name
      selected for an artifact, and intuitions about what an artifact "really" is. To
      contrast the possibility that intention serves as an essence (Bloom, P. (1996).
      Intention, history, and artifact concepts. Cognition, 60, 1-29; Bloom, P. (1998).
      Theories of artifact categorization. Cognition, 66, 87-93.) determining an
      artifact's name with the possibility that it matters through its relevance to
      discourse goals, participants in three experiments read scenarios about people
      interacting with an artifact and then judged the suitability of different names
      for it. The intention of the creator was of differing degrees of relevance to the
      communication, and the relevance of other aspects of the entity varied in a
      complementary fashion. We found that name selection was altered by the
      communicative goals of a situation, and name choice was most consistent with
      creator's intention when the situation made intention relevant to achieving those
      goals. In a fourth experiment, we used the same scenarios to test the possibility
      that intention serves as an essence determining intuitions about what an object
      "really" is. The impact of creator's intention was modulated by the discourse
      context. These findings suggest that creator's intention influences both name
      choice and intuitions about what something "really" is by virtue of its impact on
      how communicative goals are best realized.

PMID- 17187771
TI  - Multiple sensory G proteins in the olfactory, gustatory and nociceptive neurons
      modulate longevity in Caenorhabditis elegans.
AB  - The life span of the nematode Caenorhabditis elegans is under control of sensory
      signals detected by the amphid neurons. In these neurons, C. elegans expresses at
      least 13 Galpha subunits and a Ggamma subunit, which are involved in the
      transduction and modulation of sensory signals. Here, we show that loss-of
      function mutations in the Galpha subunits odr-3, gpa-1 and gpa-9, in the Ggamma
      subunit gpc-1 and the introduction of extra copies of the Galpha subunit gpa-11
      extend the life span of C. elegans. Loss-of-function of odr-3 and extra copies of
      gpa-11 act synergistically and can together extend life span more than two-fold,
      indicating that sensory signals play an important role in regulating life span.
      We show that gpa-1, gpa-11, odr-3 and gpc-1 all signal via the daf-16 FOXO family
      transcription factor. In addition, odr-3 and gpa-11 might suppress life span
      extension partially independent of the insulin/IGF-1 like receptor homologue daf
      2. Our results suggest that the previously unanticipated nociceptive ASH and/or
      ADL neurons regulate longevity. We expect that the implication of specific G
      proteins will eventually contribute to the identification of the sensory cues
      that determine the rate of aging in C. elegans.

PMID- 17187772
TI  - Sonic hedgehog in the pharyngeal endoderm controls arch pattern via regulation of
      Fgf8 in head ectoderm.
AB  - Fgf8 signalling is known to play an important role during patterning of the first
      pharyngeal arch, setting up the oral region of the head and then defining the
      rostral and proximal domains of the arch. The mechanisms that regulate the
      restricted expression of Fgf8 in the ectoderm of the developing first arch,
      however, are not well understood. It has become apparent that pharyngeal endoderm
      plays an important role in regulating craniofacial morphogenesis. Endoderm
      ablation in the developing chick embryo results in a loss of Fgf8 expression in
      presumptive first pharyngeal arch ectoderm. Shh is locally expressed in
      pharyngeal endoderm, adjacent to the Fgf8-expressing ectoderm, and is thus a
      candidate signal regulating ectodermal Fgf8 expression. We show that in cultured
      explants of presumptive first pharyngeal arch, loss of Shh signalling results in
      loss of Fgf8 expression, both at early stages before formation of the first arch,
      and during arch formation. Moreover, following removal of the endoderm, Shh
      protein can replace this tissue and restore Fgf8 expression. Overexpression of
      Shh in the non-oral ectoderm leads to an expansion of Fgf8, affecting the rostral
      caudal axis of the developing first arch, and resulting in the formation of
      ectopic cartilage. Shh from the pharyngeal endoderm thus regulates Fgf8 in the
      ectoderm and the role of the endoderm in pharyngeal arch patterning may thus be
      indirectly mediated by the ectoderm.

PMID- 17187773
TI  - Fate determination of Drosophila leg distal regions by trachealess and tango
      through repression and stimulation, respectively, of Bar homeobox gene expression
      in the future pretarsus and tarsus.
AB  - During tissue patterning, developing fields may be subdivided into several non
      overlapping domains by region-specific expression of transcription factors. In
      Drosophila leg development, the most distal segments, the pretarsus and tarsal
      segment 5 (ta5), are precisely specified by interactions between tarsus homeobox
      genes (BarH1 and BarH2) and pretarsus homeobox genes (aristaless, clawless, and
      Lim1). Here, we demonstrate that trachealess and tango, both encoding bHLH-PAS
      proteins that are required for the formation of the embryonic tracheal system,
      are essential for forming two adjacent distal segments of the leg. trachealess is
      expressed in the pretarsus and ta5, and the concerted action of trachealess and
      tango seems to modulate the activity of homeobox gene regulatory loops by
      repressing Bar in the pretarsus and activating Bar in ta5.

PMID- 17187774
TI  - The L-isoaspartyl-O-methyltransferase in Caenorhabditis elegans larval longevity
      and autophagy.
AB  - The protein L-isoaspartyl-O-methyltransferase, coded by the pcm-1 gene in
      Caenorhabditis elegans, participates in the repair of age-damaged proteins. We
      tested the ability of pcm-1-deficient nematodes to survive starvation stress as
      developmentally-arrested L1 larvae. We found that pcm-1 mutant L1 larvae do not
      survive as well as wild-type L1 larvae when incubated in M9 medium without
      nutrients. We then tested whether the starved L1 larvae could continue
      development when allowed access to food in a recovery assay. A loss of recovery
      ability with age was observed for all larvae, with little or no difference
      between the pcm-1 mutant and wild-type N2 larvae. Interestingly, when L1 larvae
      were starved in cholesterol-containing S medium or M9 medium supplemented with
      cholesterol, the survival rates of both mutant and wild-type animals nearly
      doubles, with pcm-1 larvae again faring more poorly than N2 larvae. Furthermore,
      L1 larvae cultured in these cholesterol-containing media show an increase in
      Sudan Black staining over animals cultured in M9 medium. The longevity defects of
      pcm-1 mutants previously seen in dauer larvae and here in L1 larvae suggest a
      defect in the ability of pcm-1 mutants to recycle and reuse old cellular
      components in pathways such as autophagy. Using an autophagosomal marker, we
      found evidence suggesting that the pcm-1 mutation may inhibit autophagy during
      dauer formation, suggesting that the absence of protein repair may also interfere
      with protein degradation pathways.

PMID- 17187775
TI  - Angiogenic factors stimulate tubular branching morphogenesis of sonic hedgehog
      deficient lungs.
AB  - Sonic Hedgehog (Shh)-deficient mice have a severe lung branching defect. Recent
      studies have shown that hedgehog signaling is involved in vascular development
      and it is possible that the diminished airway branching in Shh-deficient mice is
      due to abnormal pulmonary vasculature formation. Therefore, we investigated the
      role of Shh in pulmonary vascular development using Shh/Tie2lacZ compound mice,
      which exhibit endothelial cell-specific LacZ expression, and Pecam-1
      immunohistochemistry. In E11.5-13.5 Shh-deficient mice, the pulmonary vascular
      bed is decreased, but appropriate to the decrease in airway branching. However,
      when E12.5 Shh-deficient lungs were cultured for 4-6 days, the vascular network
      deteriorated compared to wild-type lungs. The expression of vascular endothelial
      growth factor (Vegf) or its receptor Vegfr2 (KDR/Flk-1) was not different between
      E12.5-13.5 Shh-deficient and wild-type lungs. In contrast, angiopoietin-1 (Ang1),
      but not Ang2 or the angiopoietin receptor Tie2, mRNA expression was downregulated
      in E12.5-E13.5 lungs of Shh null mutants. Recombinant Ang1 alone was unable to
      restore in vitro branching morphogenesis in Shh-deficient lungs. Conversely, the
      angiogenic factor fibroblast growth factor (Fgf)-2 alone or in combination with
      Ang1, increased vascularization and tubular growth and branching of Shh-deficient
      lungs in vitro. The angiogenic factors did not overcome the reduced smooth muscle
      cell differentiation in the Shh null lungs. These data indicate that early
      vascular development, mediated by Vegf/Vegfr2 signaling proceeds normally in Shh
      deficient mice, while later vascular development and stabilization of the
      primitive network mediated by the Ang/Tie2 signaling pathway are defective,
      resulting in an abnormal vascular network. Stimulation of vascularization with
      angiogenic factors such as Fgf2 and Ang1 partially restored tubular growth and
      branching in Shh-deficient lungs, suggesting that vascularization is required for
      branching morphogenesis.

PMID- 17187776
TI  - Association of a polychlorinated dibenzo-p-dioxin, a polychlorinated biphenyl,
      and DDT with diabetes in the 1999-2002 National Health and Nutrition Examination
      Survey.
AB  - The association of a polychlorinated dibenzo-p-dioxin, a polychlorinated
      biphenyl, and p,p'-DDT with diabetes was evaluated using the 1999-2002 National
      Health and Nutrition Examination Survey. Persons 20 years old and older were
      included. Relationships with diagnosed diabetes, undiagnosed diabetes
      (glycohemoglobin (HbA1c) >6.1%), and total diabetes (diagnosed plus undiagnosed)
      were tested. When all three chemicals were evaluated together for total diabetes,
      the unweighted number of participants was 1830. All three compounds were
      significantly associated with diagnosed diabetes. PCB 126 and p,p'-DDT were
      significantly associated with undiagnosed diabetes. 1,2,3,6,7,8-hexachlorodibenzo
      p-dioxin (HxCDD) was not associated with undiagnosed diabetes. When the three
      chemicals were included in a combined model for total diabetes, PCB 126>83.8pg/g
      lipid adjusted had an odds ratio of 2.57 (95% CI 1.33-4.95) compared to PCB 126 <
      or = 31.2pg/g lipid adjusted. Also significant in a combined model for total
      diabetes was p,p'-DDT 20.8-26.6ng/g lipid adjusted with an odds ratio of 2.52
      (95% CI 1.26-5.02) and p,p'-DDT >26.6ng/g lipid adjusted with an odds ratio of
      2.74 (95% CI 1.44-5.23) both compared to p,p'-DDT < or = 20.7ng/g lipid adjusted.
      HxCDD was not associated with total diabetes in a combined model. When
      participants with poor liver function and poor kidney function were removed from
      the analysis, the combined model for total diabetes produced similar results with
      PCB 126 and p,p'-DDT having been significantly associated, and HxCDD not having
      been associated. These findings add to the list of chemicals found to be
      associated with diabetes in the 1999-2002 National Health and Nutrition
      Examination Survey.

PMID- 17187777
TI  - Aspirin restores normal baroreflex function in hypercholesterolemic rats by its
      antioxidative action.
AB  - Besides its well-known effects on platelet aggregation, aspirin has been
      suggested to be an antioxidant and is also known to improve the lipid profile. In
      the present study we tested the hypothesis that aspirin by its antioxidant
      effect, improves haemodynamic profile and baroreflex sensitivity in rat model of
      hypercholesterolemia. Hypercholesterolemia was induced in Wistar rats by feeding
      1% cholesterol rich diet for 10 weeks. Lipid profile, lipid peroxidation and
      reduced glutathione were estimated in serum. Haemodynamic changes and baroreflex
      were measured in anaesthetized rats. Hypercholesterolemic rats showed significant
      increase in total cholesterol, low-density lipoprotein-cholesterol (LDL-C), very
      low-density lipoprotein-cholesterol (VLDL-C) and atherogenic index and
      significant decrease in high-density lipoprotein-cholesterol (HDL-C). Significant
      rise in blood pressure, heart rate and attenuation of baroreflex sensitivity were
      also found in hypercholesterolemic rat. Aspirin in the dose of 100 mg/kg showed
      significant decrease in total cholesterol, LDL-C, VLDL-C and atherogenic index
      and significant increase in HDL-C. Aspirin treatment prevented the rise in blood
      pressure, heart rate and significantly improved baroreflex sensitivity in
      hypercholesterolemic rats. Hypercholesterolemic rats showed free radical
      generation, evident by a significant increase in serum lipid peroxidation and
      significant reduction in serum reduced glutathione content. Aspirin treatment
      significantly decreased lipid peroxidation and significantly increased reduced
      glutathione content. We have demonstrated that aspirin improves baroreflex
      response and prevents the rise in blood pressure and heart rate possibly by
      reducing sympathetic activity due to its antioxidant effect in experimentally
      induced hypercholesterolemic rats.

PMID- 17187778
TI  - Eukaryotic translation initiation factor 5A induces apoptosis in colon cancer
      cells and associates with the nucleus in response to tumour necrosis factor alpha
      signalling.
AB  - Eukaryotic translation initiation factor 5A (eIF5A) is thought to function as a
      nucleocytoplasmic shuttle protein. There are reports of its involvement in cell
      proliferation, and more recently it has also been implicated in the regulation of
      apoptosis. In the present study, we examined the effects of eIF5A over-expression
      on apoptosis and of siRNA-mediated suppression of eIF5A on expression of the
      tumour suppressor protein, p53. Over-expression of either eIF5A or a mutant of
      eIF5A incapable of being hypusinated was found to induce apoptosis in colon
      carcinoma cells. Our results also indicate that eIF5A is required for expression
      of p53 following the induction of apoptosis by treatment with Actinomycin D.
      Depiction of eIF5A localization by indirect immunofluorescence has indicated, for
      the first time, that the protein is rapidly translocated from the cytoplasm to
      the nucleus by death receptor activation or following treatment with Actinomycin
      D. These findings collectively indicate that unhypusinated eIF5A may have pro
      apoptotic functions and that eIF5A is rapidly translocated to the nucleus
      following the induction of apoptotic cell death.

PMID- 17187779
TI  - Critical involvement of ILK in TGFbeta1-stimulated invasion/migration of human
      ovarian cancer cells is associated with urokinase plasminogen activator system.
AB  - The present study investigated the role of integrin-linked kinase (ILK) in
      TGFbeta1-stimulated invasion/migration of human ovarian cancer cells. We
      investigated TGFbeta1 regulation of ILK, and effects of ILK knockdown on TGFbeta1
      stimulated invasion/migration and the associated proteinase systems, urokinase
      plasminogen activator (uPA) and matrix metalloproteinases (MMPs) in SKOV3 cells.
      TGFbeta1 stimulated ILK kinase activity, and had no effect on ILK protein/mRNA
      levels. Transient transfection of an ILK-specific siRNA (ILK-H) reduced ILK
      protein level, mRNA level and kinase activity. ILK knockdown by ILK-H suppressed
      the basal and TGFbeta1-stimulated invasion and migration. Further, ILK-H reduced
      the basal and TGFbeta1-stimulated secretion of uPA, and increased the secretion
      of its inhibitor (PAI-1). Conversely, ILK-H did not affect TGFbeta1-stimulated
      secretion of MMP2 and its cell-associated activator MT1-MMP. Additionally,
      TGFbeta1 activated Smad2 phosphorylation, and this was not affected by ILK
      knockdown. Earlier reports indicate that Smad2 activation increased the
      expression of MMP2 and MT1-MMP. Thus, TGFbeta1 may act through ILK-independent
      and Smad2-dependent signaling in regulating MMP2 and MT1-MMP in SKOV3 cells.
      Collectively, this study suggests that ILK serves as a key mediator in TGFbeta1
      regulation of uPA/PAI-1 system critical for the invasiveness of human ovarian
      cancer cells. And ILK is a potential target for cancer therapy.

PMID- 17187781
TI  - Reduced expression of PSA-NCAM in the hippocampus and piriform cortex of the R6/1
      and R6/2 mouse models of Huntington's disease.
AB  - Cognitive deficits and impaired olfactory function are observed in early stages
      of Huntington's disease (HD). The polysialylated form of the neural cell adhesion
      molecule (PSA-NCAM) is strongly associated with plastic events in the brain.
      During adulthood, it is most abundantly expressed in the hippocampus and the
      piriform cortex, which are involved in cognition and olfaction, respectively. We
      show that the numbers of PSA-NCAM-positive cells in the hippocampus and piriform
      cortex are dramatically reduced in the R6/1 and the R6/2 mouse models of HD. We
      hypothesize that the decrease in NCAM polysialylation reflects an impaired
      plasticity and might underlie some of the early symptoms in HD.

PMID- 17187782
TI  - Hypoxia induces the activation of human hepatic stellate cells LX-2 through TGF
      beta signaling pathway.
AB  - Hypoxia is a common environmental stress factor and is also associated with
      various physiological and pathological conditions such as fibrogenesis. The
      activation of hepatic stellate cells (HSCs) is the key event in the liver
      fibrogenesis. In this study, the behavior of human HSCs LX-2 in low oxygen
      tension (1% O2) was analyzed. Upon hypoxia, the expression of HIF-1alpha and VEGF
      gene was induced. The result of Western blotting showed that the expression of
      alpha-SMA was increased by hypoxic stimulation. Furthermore, the expression of
      MMP-2 and TIMP-1 genes was increased. Hypoxia also elevated the protein
      expression of the collagen type I in LX-2 cells. The analysis of TGF-beta/Smad
      signaling pathway showed that hypoxia potentiated the expression of TGF-beta1 and
      the phosphorylation status of Smad2. Gene expression profiles of LX-2 cells
      induced by hypoxia were obtained by using cDNA microarray technique.

PMID- 17187783
TI  - The S. cerevisiae Yap1 and Yap2 transcription factors share a common cadmium
      sensing domain.
AB  - Towards elucidating the function of Yap2, which remains unclear, we have taken
      advantage of the C-terminal homology between Yap1 and Yap2. Swapping domains
      experiments show that the Yap2 C-terminal domain functionally substitutes for the
      homologous Yap1 domain in the response to Cd, but not to H2O2. We conclude that
      specificity determinants of the Cd response are encoded within both Yap1 and Yap2
      C-terminus, whereas those required for H2O2 response are only present in the Yap1
      C-terminus. Furthermore, our results identify FRM2 as Cd-responsive Yap2 target
      and indicate a possible role of this protein in regulating a metal stress
      response.

PMID- 17187780
TI  - At-level neuropathic pain is induced by lumbosacral ventral root avulsion injury
      and ameliorated by root reimplantation into the spinal cord.
AB  - Neuropathic pain is common after traumatic injuries to the cauda equina/conus
      medullaris and brachial plexus. Clinically, this pain is difficult to treat and
      its mechanisms are not well understood. Lesions to the ventral roots are common
      in these injuries, but are rarely considered as potential contributors to pain.
      We examined whether a unilateral L6-S1 ventral root avulsion (VRA) injury in
      adult female rats might elicit pain within the dermatome projecting to the
      adjacent, uninjured L5 spinal segment. Additionally, a subset of subjects had the
      avulsed L6-S1 ventral roots reimplanted (VRA+Imp) into the lateral funiculus post
      avulsion to determine whether this neural repair strategy elicits or ameliorates
      pain. Behavioral tests for mechanical allodynia and hyperalgesia were performed
      weekly over 7 weeks post-injury at the hindpaw plantar surface. Allodynia
      developed early and persisted post-VRA, whereas VRA+Imp rats exhibited allodynia
      only at 1 week post-operatively. Hyperalgesia was not observed at any time in any
      experimental group. Quantitative immunohistochemistry showed increased levels of
      inflammatory markers in laminae III-V and in the dorsal funiculus of the L5
      spinal cord of VRA, but not VRA+Imp rats, specific to areas that receive
      projections from mechanoreceptive, but not nociceptive, primary afferents. These
      data suggest that sustained at-level neuropathic pain can develop following a
      pure motor lesion, whereas the pain may be ameliorated by acute root
      reimplantation. We believe that our findings are of translational research
      interest, as root implantation surgery is emerging as a potentially useful
      strategy for the repair of cauda equina/conus medullaris injuries.

PMID- 17187784
TI  - Danggui buxue tang--a Chinese herbal decoction activates the phosphorylations of
      extracellular signal-regulated kinase and estrogen receptor alpha in cultured MCF
      7 cells.
AB  - Danggui buxue tang (DBT), a Chinese herbal decoction used to treat ailments in
      women, contains radix Astragali (Huangqi; RA) and radix Angelicae Sinensis
      (Danggui; RAS). The weight ratio of RA to RAS used in DBT must be 5:1 as
      stipulated as early as AD 1247; however, DBT's mechanism of action has never been
      described. Here, the estrogenic effects of DBT were investigated by determining
      the phosphorylations of estrogen receptor alpha (ER alpha) and extracellular
      signal-regulated kinase 1/2 (Erk1/2) in cultured MCF-7 cells. The application of
      DBT triggered the phosphorylation of ER alpha and Erk1/2 in a time-dependent
      manner. In contrast to the effect of estrogen, DBT triggered ER alpha
      phosphorylation at both S118 and S167. This DBT-specific phosphorylation was not
      triggered by an extract of one of the individual herbs, or by mixing the extracts
      of RA and RAS. DBT-induced downstream signals are described here. These signals
      suggest the uniqueness of this Chinese herbal decoction that requires a well
      defined formulation.

PMID- 17187785
TI  - On the origin and evolution of vertebrate and viral profilins.
AB  - The three dimensional structures of profilins from invertebrates and vertebrates
      are remarkably similar despite low sequence similarity. Their evolutionary
      relationship remains thus enigmatic. A phylogenetic analysis of profilins from
      Deuterostoma indicates that profilin III and IV isoforms each form distinct
      groups. Profilin IV is most related to invertebrate profilins and originated
      prior to vertebrate evolution whereas separation of profilin I, II and III
      isoforms occurred early in vertebrate evolution. Viral profilins are most similar
      to profilin III. In silico analysis of representative profilin gene structures
      corroborates the phylogenetic result and we discuss this in terms of biochemical
      differences.

PMID- 17187786
TI  - Differential requirement of MKK4 and MKK7 in JNK activation by distinct scaffold
      proteins.
AB  - Different scaffold proteins play distinct roles in various signaling pathways by
      recruiting different downstream molecules. Here, using MKK4(-/-) and MKK4(-/-)/7(
      /-) murine embryonic fibroblast cells, we examined differential employment of
      MKK4 and MKK7 by scaffold proteins Axin, Dvl, and Epstein-Barr virus latent
      membrane protein-1 (LMP-1) in mediating JNK activation. We present evidence that
      Axin depends mainly on MKK7 for activation of JNK, while Dvl depends almost
      equally on MKK4 and MKK7 for JNK activation, In contrast, LMP-1-induced JNK
      activation is primarily dependent on MKK4. Our results demonstrate that Axin,
      Dvl, and LMP-1 differentially utilize MKK4 and MKK7 for JNK activation.

PMID- 17187787
TI  - UBPy/MSJ-1 system during male germ cell progression in the frog, Rana esculenta.
AB  - mUBPy (mouse ubiquitin specific processing protease) is a de-ubiquitinating
      enzyme expressed in mouse testis and brain. In testis, it interacts with the DnaJ
      protein MSJ-1 (mouse sperm cell specific DnaJ first homologue), a molecular
      chaperone expressed in spermatids and spermatozoa. Since MSJ-1 is conserved among
      vertebrates, to demonstrate an evolutionarily conserved function of UBPy/MSJ-1
      system, we assayed mUBPy presence in the anuran amphibian, the frog, Rana
      esculenta, during the annual sexual cycle. By Western blot we have detected a
      specific signal of 126kDa in testis and isolated spermatozoa. During the annual
      sexual cycle, the signal gradually increases as soon as spermatogenesis resumes
      after the winter stasis. Using immunocytochemistry, we have localized the protein
      in spermatids and spermatozoa. In conclusion, UBPy/MSJ-1 system is available in
      R. esculenta testis suggesting a conserved fundamental function in
      spermatogenesis and sperm formation.

PMID- 17187789
TI  - TVT versus TOT for surgical treatment of female stress urinary incontinence.

PMID- 17187788
TI  - Yolk androgens and embryo sex: maternal effects or confounding factors?
AB  - Maternal effects occur when offspring phenotype is affected by environmental
      factors experienced by the mother and, in egg-laying species, are often mediated
      via egg resources. There is currently great interest among behavioural ecologists
      in maternally allocated yolk androgens, especially their relationship with
      offspring sex and development. Such studies need embryonic tissue for sexing,
      however, requiring eggs to be incubated (usually for 3 days). Therefore, there
      are concerns about whether the androgen concentrations assayed reflect those
      allocated by the mother. In addition, studies showing sex biases in maternal
      allocation of androgens could be confounded if male and female embryos uptake or
      metabolise androgens at different rates. We ran a series of experiments using
      zebra finch (Taeniopygia guttata) eggs to address these potential confounding
      factors. First we showed, using eggs naturally incubated for up to 5 days, that
      eggs containing embryos had lower yolk androgen concentrations than eggs that had
      failed to form embryos. We then tested various hypotheses for this difference
      using controlled incubation treatments. Our results suggested that (a) embryo
      development causes the yolk to become progressively more diluted with albumin;
      and (b) between 3 and 5 days of incubation embryos start uptaking or metabolising
      androgens. Crucially, we found no decline in yolk androgen concentration at 3
      days incubation, and no evidence for sex-specific rates of uptake or metabolism
      of androgens. This strongly suggests that yolk androgen levels up to 3 days
      incubation do reflect those allocated by the mother, and that studies of sex
      biased maternal allocation of yolk androgens are not confounded by sex
      differences in embryo development.

PMID- 17187790
TI  - Gametes intrauterine transfer versus in vitro fertilization for poor responders.

PMID- 17187791
TI  - Skeletal muscle metastatic and pelvic leiomyosarcomas following hysterectomy.

PMID- 17187792
TI  - Acquiring human embryos for stem-cell research.
AB  - Human tissue engineering and regenerative medicine may be considerably advanced
      by embryonic stem-cell research and cell line development, to provide preventive
      means, cures and treatment strategies for a range of debilitating conditions and
      injuries. Research may result in embryos from which stem-cells are derived losing
      viability, which offends some religious convictions. The different status
      religions and laws may attribute to embryos serves different purposes and results
      from different approaches. Neither need depend on, nor impose itself on, the
      other. Embryos surplus to IVF patients' needs may be donated to research with
      appropriate consent. In some circumstances, it may be ethical to ask patients to
      make their fresh embryos available for research. Prohibitions against
      deliberately creating embryos for research purposes are common, but not
      universally adopted, and are being challenged. Women who donate ova require
      information about risks, which for women considering donation for research may
      not be balanced by compensating benefits.

PMID- 17187793
TI  - Incidental adnexal masses removed at cesarean section.

PMID- 17187795
TI  - Affirm VP III in the detection and identification of Candida species in
      vaginitis.

PMID- 17187796
TI  - Favorable outcome following emergency second trimester cerclage.
AB  - BACKGROUND: To evaluate the outcome of midtrimester emergency cerclage with or
      without bulging of membranes. METHODS: A retrospective cohort study of 99 women
      who underwent emergency second trimester cerclage (16-27 gestational weeks). In
      75 women the cervix was dilated and effaced but without bulging of membranes
      (group 1), and in 24 women the dilation and effacement of the cervix were
      accompanied by bulging of membranes into the vagina in an hourglass formation
      (group 2). McDonald technique was applied in all patients. RESULTS: Prolongation
      of pregnancy was significantly longer in group 1 compared to group 2 (14.3+/-6.5
      vs 9.3+/-4.8 weeks, p=0.007). The mean gestational age at delivery was
      significantly higher in group 1 compared to group 2 (34.6+/-4.6 vs 29.5+/-3.2
      weeks, p=0.001). The incidence of chorioamnionitis was higher in group 2 compared
      to group 1 but statistically insignificant (25% vs 15%, p=0.2). The overall
      neonatal survival was 83% (82 out of 99 neonates), without statistical difference
      between the two groups (86% in group 1 and 71% in group 2, p=0.2). CONCLUSIONS:
      Favorable neonatal outcome may be accomplished in patients with cervical
      incompetence in the second trimester of pregnancy following cervical emergency
      suturing even performed when the membranes are bulging through the cervix into
      the vagina.

PMID- 17187797
TI  - Increased leukocyte distribution in the pre-clinical stage of pre-eclampsia.

PMID- 17187798
TI  - Cesarean births in Taiwan.
AB  - OBJECTIVE: To evaluate the use of cesarean delivery in Taiwan by comparing local
      clinical indications with those in international cohorts. METHODS: In-patient
      claims from the National Health Insurance (NHI) in Taiwan were analyzed.
      Indications for cesarean delivery were evaluated with primary diagnosis codes and
      procedure codes from the NHI dataset. To produce a stable numerator for cesarean
      section, 3 years (1998-2000) of claims for cesarean delivery were abstracted and
      annualized. RESULTS: Rates ranged between 27.3% and 28.7% for primary cesarean
      delivery and were below 5% for vaginal birth after a cesarean section (VBAC).
      Compared with rates in other countries, rates for overall and primary cesarean
      section as well as for VBAC were significantly higher in medical centers in
      Taiwan (P<0.001). However, the clinics contributed the most to the difference in
      both overall and primary cesarean rates. The most common indication for cesarean
      section was prior cesarean section (43.3%-45.5%), followed by malpresentation
      (19.6%-23.4%). The proportion of fetuses with malpresentation delivered by
      cesarean section in Taiwan was 7.9%, almost twice the upper limit expected for
      all pregnancies as indicated in international studies. CONCLUSION: It is
      important to use appropriately documented data and to compare them with
      international data when monitoring local obstetric practices. The
      disproportionately high cesarean delivery rates in Taiwan may hold major lessons
      for the many countries contemplating or having universal health insurance
      coverage with a similar mix of providers.

PMID- 17187799
TI  - Duhrssen incision to prevent a high cervical tear during mid-trimester abortion.

PMID- 17187800
TI  - Cesarean section on request in a developing country.
AB  - OBJECTIVE: To assess the prevalence of cesarean sections (CSs) and women's
      reasons for requesting the procedure in a developing country. METHOD: Pregnant
      women scheduled for elective CS were interviewed to determine whether the
      procedure was requested by them or suggested by a physician. The women who
      personally requested a CS filled out questionnaires before surgery and at the
      postnatal visit 6 weeks later, and their answers were analyzed. RESULTS: The
      prevalence of CS on request was 4.4%. Previous infertility and advanced maternal
      age at first pregnancy were the most common reasons for requesting a CS, but most
      women said they would prefer a vaginal delivery in subsequent pregnancies.
      CONCLUSION: The women who requested a CS in this study did so for reasons
      different from those put forth by women in developed countries. The view that a
      CS is the surest way toward a live birth was the critical factor underlying their
      choice.

PMID- 17187801
TI  - Pyridoxine (vitamin B6) therapy for premenstrual syndrome.

PMID- 17187802
TI  - Sonohysterography versus transvaginal sonography for screening of patients with
      abnormal uterine bleeding.
AB  - OBJECTIVES: To compare the accuracy of saline infusion sonohysterography (SIS)
      with transvaginal sonography (TVS) for the screening of causes of abnormal
      uterine bleeding (AUB) in out-patients. METHODS: 81 patients with AUB were
      studied. All cases who were examined with TVS, were further investigated with SIS
      using saline as contrast medium, finally hysteroscopy was used as the gold
      standard. RESULTS: TVS had sensitivity of 72%, specificity of 92%, positive
      predictive value of 94% and negative predictive value of 65%, while SIS had
      sensitivity of 94.1%, specificity of 95%, positive predictive value of 96% and
      negative predictive value of 90%. TVS had kappa measure of agreement of 0.60
      while 0.86 was reported for SIS. CONCLUSIONS: In this study SIS was more
      sensitive and specific in diagnosing polyp, myoma and adenomyosis with high
      positive and negative predictive value. Furthermore, results obtained by SIS
      demonstrate more agreement with that obtained by hysteroscopy than TVS.

PMID- 17187803
TI  - Risk scoring for adnexal masses and endoscopic management.

PMID- 17187804
TI  - Induction of labor with misoprostol or oxytocin in Tanzania.

PMID- 17187805
TI  - Mechanical stress during phonation in a self-oscillating finite-element vocal
      fold model.
AB  - The stress information during phonation in the vocal folds is helpful in
      understanding the etiologies of vocal trauma and its related vocal diseases, such
      as nodules. In this paper, a self-oscillating finite-element model, which
      combines aerodynamic properties, tissue mechanics, airflow-tissue interactions,
      and vocal fold collisions, was used to simulate the vocal fold vibration during
      phonation. The spatial and temporal characteristics of mechanical stress in the
      vocal folds were predicted by this model. Temporally, it was found that
      mechanical stress periodically undulates with vibration of the vocal folds and
      that vocal fold impact causes a jump in the normal stress value. Spatially, the
      normal stress is significantly higher on the vocal fold surface than inside of
      the vocal folds. At the midpoint of the medial surface, the peak-to-peak
      amplitude of the normal stress reaches its maximum value. Using different lung
      pressures (0-1.5kPa) to drive the self-oscillating model, we found that lower
      lung pressure can effectively decrease the mechanical stress in the vocal folds.
      This study supports the fatigue damage hypothesis of vocal trauma. With this
      hypothesis and the numerical simulation in this study, the clinical observations
      of vocal fold trauma risk can be explained. This implies the mechanical stress
      predicted by this self-oscillating model could be valuable for predicting,
      preventing, and treating vocal fold injury.

PMID- 17187806
TI  - The apparent mass of the seated human exposed to single-axis and multi-axis whole
      body vibration.
AB  - Most workplaces where workers are exposed to whole-body vibration involves
      simultaneous motion in the fore-and-aft (x-), lateral (y-) and vertical (z-)
      directions. Previous studies reporting the biomechanical response of people
      exposed to vibration have almost always used single-axis vibration stimuli. This
      paper reports a study where apparent masses of 15 subjects were measured whilst
      exposed to single-axis and tri-axial whole-body vibration. Each subject was
      exposed to 28 vibration conditions comprising every combination of single-axis
      and tri-axial vibration with magnitudes of 0.4 and 0.8 ms(-2) r.m.s. in each
      direction, once with backrest contact and once without backrest contact. Results
      show that increasing the magnitude of vibration in directions orthogonal to that
      being measured affects the apparent mass, causing a reduction in the resonance
      frequency as the total magnitude of vibration increases. It is demonstrated that
      the apparent mass resonance frequency is a function of the total vibration
      magnitude in all axes rather than a function of the vibration magnitude in the
      direction being measured. It is also shown that, for individuals, the frequency
      of the peak in the apparent mass in one direction is not related to the frequency
      of the peak in another direction. It is concluded that more complex biomechanical
      models are required in order to simulate human response to multi-axis vibration.

PMID- 17187807
TI  - Validation of a liquid chromatography-mass spectrometry multi-residue method for
      the simultaneous determination of sulfonamides, tetracyclines, and pyrimethamine
      in milk.
AB  - A multiresidue method suitable for confirmation and determination of six
      sulfonamides (SAs), three tetracyclines (TCs), and pyrimethamine (PYR) in cow
      milk was validated. Milk samples were extracted using copolymer Oasis HLB solid
      phase extraction (SPE) and analyzed by liquid chromatography-electrospray mass
      spectrometry with positive ion mode. Estimated method detection limits (MDL) and
      method quantitation limits (MQL) ranged from 0.48 to 2.64 and 0.61 to 8.64ng/mL,
      respectively. These values are far lower than the maximum residue limits (MRLs)
      established by several control authorities. Excellent linear dynamic range was
      observed from the method quantitation limits to 300ng/mL with correlation
      coefficients better than 0.9900 for all compounds. The method was accurate with
      recoveries ranging from 72.01 to 97.39%. Good intra-precision and intermediate
      precision were obtained with RSD better than 11.08%. The method is fairly robust
      with sample pH being the only critical control point.

PMID- 17187808
TI  - New materials in sorptive extraction techniques for polar compounds.
AB  - This paper provides an overview of the new developments in material and format
      technology that improve the extraction of polar compounds in several extraction
      techniques. They mainly include solid-phase extraction, but there are also other
      sorptive extraction techniques, such as stir bar sorptive extraction and solid
      phase microextraction that use either fibers or in-tube devices. We focus on new
      synthesised materials that are both commercially available and "in-house". Most
      novel materials that enhance the extraction of polar compounds are hydrophilic
      and have large specific surface area; however, we also cover other leading
      technologies, such as sol-gel or monolith. We describe the morphological and
      chemical properties of these new sorbents so that we can better understand them
      and relate them to their capability of retaining polar compounds. We discuss the
      extraction efficiency for polar compounds when these polymers are used as
      sorptive material and compare them to other materials. We also mention some
      representative examples of applications.

PMID- 17187809
TI  - A sensitive and selective method for the detection of diazepam and its main
      metabolites in urine by gas chromatography-tandem mass spectrometry.
AB  - A gas chromatography-tandem mass spectrometry method for detection of diazepam,
      nordazepam and oxazepam is presented. The method associates electron capture
      ionization and multiple reaction monitoring (MRM). No derivatization is
      performed; oxazepam undergoes thermal degradation during chromatographic
      injection and is thus quantified via its decomposition product. The negative
      molecular ions are so stable that they do not dissociate when collision is
      performed under "classical" conditions (i.e. with argon as collision gas). With
      xenon as collision gas, the energy transfer is sufficient to provide two product
      ions for diazepam and nordazepam and one product ion for the decomposition
      product of oxazepam. The sample preparation part involves liquid/liquid
      extraction with TOXI-TUBES A extraction tubes; it provides recovery yields
      between 68 and 95%, depending of the benzodiazepine considered, with coefficients
      of variation below 6% for 10 samples. The applicability of the method was
      demonstrated on urine extracts. From 1 mL of urine, the method provides
      quantitation limits of 0.15 ng/mL for diazepam, 1.0 ng/mL for nordazepam and 1.5
      ng/mL for oxazepam. Mechanisms of dissociation of M*(-) ions of benzodiazepines
      are suggested.

PMID- 17187810
TI  - Development and validation of a method for air-quality and nuisance odors
      monitoring of volatile organic compounds using multi-sorbent adsorption and gas
      chromatography/mass spectrometry thermal desorption system.
AB  - An analytical method based on thermal desorption (TD) coupled to gas
      chromatography (GC) and mass spectrometry detection (MS) has been developed and
      validated for the determination of a wide range of odor nuisance and air-quality
      volatile organic compounds (VOC) in air. New generation isocyanates, isocyanato-
      and isothiocyanatocyclohexane, have been included for the first time as target
      compounds due to their high occurrence in air samples. A dynamic air sampling
      method to trap gas and vapor on multi-sorbent tubes using portable pump equipment
      has been also developed. Sorbent tubes were filled with Carbotrap (70mg),
      Carbopack X (100mg) and Carboxen-569 (90mg). Validation of the TD-GC-MS method
      showed good selectivity, sensibility and precision according to Compendium Method
      TO-17 (US Environment Protection Agency) criteria. Limits of detection (signal-to
      noise=3, ng in tube) ranges were 0.004-0.03ng (alcanes), 0.001-0.1ng (aromatics),
      0.03-14ng (aldehydes), 0.003-7ng (alcohols), 0.003-0.04ng (chlorides), 0.02-0.5ng
      (esters), 0.002-0.1ng (ketones), 0.01-0.53ng (terpenes), 14-97ng (amides), 0.2
      10ng (isocyanates) and 0.001ng (carbon disulfide). The linear dynamic range was
      over 3-5 orders of magnitude, depending of the VOC. TD-GC-MS analysis was
      reproducible, with relative standard deviation (n=5) within 20%. VOCs
      breakthrough examination showed no significant losses when about 2000ng standard
      was prepared. In order to evaluate the performance of the developed method on
      real samples, several industrial and urban air samples were analysed. VOCs were
      found to be stable on the sorbent tubes for at least 1 week when stored at 4
      degrees C.

PMID- 17187811
TI  - Requirements for prediction of peptide retention time in reversed-phase high
      performance liquid chromatography: hydrophilicity/hydrophobicity of side-chains
      at the N- and C-termini of peptides are dramatically affected by the end-groups
      and location.
AB  - The value of reversed-phase high-performance liquid chromatography (RP-HPLC) and
      the field of proteomics would be greatly enhanced by accurate prediction of
      retention times of peptides of known composition. The present study investigates
      the hydrophilicity/hydrophobicity of amino acid side-chains at the N- and C
      termini of peptides while varying the functional end-groups at the termini. We
      substituted all 20 naturally occurring amino acids at the N- and C-termini of a
      model peptide sequence, where the functional end-groups were N(alpha)-acetyl-X-
      and N(alpha)-amino-X- at the N-terminus and -X-C(alpha)-carboxyl and -X-C(alpha)
      amide at the C-terminus. Amino acid coefficients were subsequently derived from
      the RP-HPLC retention behaviour of these peptides and compared to each other as
      well as to coefficients determined in the centre of the peptide chain (internal
      coefficients). Coefficients generated from residues substituted at the C-terminus
      differed most (between the -X-C(alpha)-carboxyl and -X-C(alpha)-amide peptide
      series) for hydrophobic side-chains. A similar result was seen for the N(alpha)
      acetyl-X- and N(alpha)-amino-X- peptide series, where the largest differences in
      coefficient values were observed for hydrophobic side-chains. Coefficients
      derived from substitutions at the C-terminus for hydrophobic amino acids were
      dramatically different compared to internal coefficients for hydrophobic side
      chains, ranging from 17.1 min for Trp to 4.8 min for Cys. In contrast,
      coefficients derived from substitutions at the N-terminus showed relatively small
      differences from the internal coefficients. Subsequent prediction of peptide
      retention time, within an error of just 0.4 min, was achieved by a predictive
      algorithm using a combination of internal coefficients and coefficients for the C
      terminal residues. For prediction of peptide retention time, the sum of the
      coefficients must include internal and terminal coefficients.

PMID- 17187813
TI  - Purification of plant viral and satellite double-stranded RNAs on DEAE monoliths.
AB  - Replicative double-stranded RNA (dsRNA) is useful in preliminary identification
      of Cucumber mosaic virus and its satellite RNA (satRNA). This plant pathogen
      complex yields sufficient quantity of the replicative RNA form that can be
      isolated by chromatography on chemically unmodified graded cellulose powder (CF
      11). In this work, much faster and more efficient procedure using DEAE monoliths
      was developed in which dsRNA was separated from other species in total nucleic
      acids extract originating from the infected plant tissue. The developed
      chromatographic method revealed the pathogens' presence in only 15 min, avoiding
      nucleic acid precipitation and electrophoretic analysis.

PMID- 17187812
TI  - Towards the certification of the purity of calibrant reference materials for
      thyroid hormones: a chicken and egg dilemma.
AB  - The certification of the purity of CRMs intended for calibration, where no other
      certified material already exists for comparison, raises principle questions on
      how to determine the purity of a "first" calibrant in the calibration hierarchy.
      We developed and certified two calibration CRMs for their purity in thyroid
      hormones taking into consideration inorganic residues, residual solvents and
      organic impurities detectable by HPLC-UV and HPLC-MS. IRMM-468 was certified for
      a thyroxine (T(4)) mass fraction of 98.6+/-0.7% and IRMM-469 was certified for a
      3,3',5-triiodothyronine (T(3)) mass fraction of 97.1+/-0.7%. The approach we used
      aims to determine the purity of these two CRMs to the best of our knowledge and
      taking all scientific aspects properly into account for the estimation of an
      uncertainty related to the stated purity.

PMID- 17187815
TI  - Residence time distribution for electrokinetic flow through a microchannel
      comprising a bundle of cylinders.
AB  - The electrokinetic flow of an electrolyte solution through a microchannel that
      comprises a bundle of cylinders is investigated for the case of constant surface
      potential. The system under consideration is simulated by a unit cell model, and
      analytical expressions for the flow field and the corresponding residence time
      distribution under various conditions are derived. These results are readily
      applicable to the assessment of the performance of a microreactor such as that
      which comprises a bundle of optical fibers. Numerical simulations are conducted
      to investigate the influences of the key parameters, including the thickness of
      the double layer, the strength of the applied electric field, the magnitude of
      the applied pressure gradient, and the characteristic sizes of a microchannel, on
      the residence time distribution. We show that the following could result in a
      shorter residence time: thin double layer, strong applied electric field, large
      applied pressure gradient, and small number of cylinders. Based on the thickness
      of the double layer, criteria are proposed for whether the flow field can be
      treated as a laminar flow or as a plug flow, two basic limiting cases in reactor
      design.

PMID- 17187814
TI  - Ketopinic acid and diisoproylideneketogulonic acid as chiral ion-pair selectors
      in capillary electrophoresis. Enantiomeric impurity analysis of S-timolol and
      1R,2S-ephedrine.
AB  - 1S,4R-(+)-ketopinic acid [(+)-KPA] has been introduced as a chiral selector for
      the separation of pharmacologically active amines by non-aqueous capillary
      electrophoresis (NACE). (+)-KPA gave enantioresolution for most of the compounds
      previously separated by 2R,3S,4R,5S-(-)-2,3:4,6-di-O-isopropylidene-2-keto-L
      gulonic acid [(-)-DIKGA], but with a reversed migration order. A complete
      enantioresolution (Rs=4.2) was obtained for timolol, a compound that could not be
      resolved using (-)-DIKGA as the selector. Thus, (+)-KPA was evaluated for the
      enantiomeric purity determination of S-timolol. A method based on pre
      concentration by transient isotachophoresis (tITP) provided a limit of detection
      (LOD) of 0.2% R-timolol in S-timolol samples. Because of the lack of
      enantioresolution of ephedrine when (+)-KPA was used as the selector, a method
      with (-)-DIKGA has been developed and validated for determination of the
      enantiomeric purity of the 1R,2S enantiomer. The method gave good precision and
      accuracy with an LOD (S/N=3) of 0.033% for the enantiomeric impurity 1S,2R
      ephedrine.

PMID- 17187816
TI  - Preparation and electrocatalytic properties of Pt-SiO2 nanocatalysts for ethanol
      electrooxidation.
AB  - Due to their high stability in general acidic solutions, SiO(2) nanoparticles
      were selected as the second catalyst for ethanol oxidation in sulfuric acid
      aqueous solution. Pt-SiO(2) nanocatalysts were prepared in this paper. The
      micrography and elemental composition of Pt-SiO(2) nanoparticles were
      characterized by scanning electron microscopy and energy dispersive X-ray
      spectroscopy, respectively. The electrocatalytic properties of Pt-SiO(2)
      nanocatalysts for ethanol oxidation were investigated by cyclic voltammetry.
      Under the same Pt loading mass and experimental conditions for ethanol oxidation,
      Pt-SiO(2) nanocatalysts show higher activity than PtRu/C (E-Tek), Pt/C (E-Tek),
      and Pt catalysts. Additionally, Pt-SiO(2) nanocatalysts possess good anti
      poisoning ability. The results indicate that Pt-SiO(2) nanocatalysts may have
      good potential applications in direct ethanol fuel cells.

PMID- 17187817
TI  - Kinetic modeling of adsorption of di-2-pyridylketone salicyloylhydrazone on
      silica gel.
AB  - The kinetics of DPKSH (di-2-pyridylketone salicyloylhydrazone) adsorption onto
      silica gel has been investigated at (25+/-1) degrees C and pH 1 and 4.7. The
      kinetics of adsorption of DPKSH is discussed using three kinetic models, the
      first-order Lagergren model, the pseudo-second-order model, and the intraparticle
      diffusion model. The adsorption of DPKSH, at pH 1 and 4.7, onto silica gel
      proceeds according to the pseudo-second-order model and the correlation
      coefficients were very close to 1. The intraparticle diffusion of DPKSH molecules
      within the silica gel particles was identified as the rate-limiting step. The
      parameters of the pseudo-second-order model are q(max,calc)=1.02 x 10(-4) and 1.5
      x 10(-4) g DPKSH/g silica; k(2)=3.01 x 10(4) and 9.67 x 10(4) h(-1)g silica/g
      DPKSH, respectively, for pH 1 and 4.7.

PMID- 17187818
TI  - Comparison of sample fixation and the use of LDS-751 or anti-CD45 for leukocyte
      identification in mouse whole blood for flow cytometry.
AB  - Flow cytometry methods used to measure leukocyte function often entail sample
      preparation procedures that cause artifactual cell activation. To avoid leukocyte
      activation by isolation techniques, some preparation methods use fluorescent
      markers to discriminate leukocytes from erythrocytes in whole blood. One of these
      markers, laser dye styryl-751(LDS-751), has been used to distinguish leukocytes
      by staining nucleic acid, but has been found to stain other blood cells and dead
      cells indiscriminately. Thus, LDS-751 may not be an appropriate reagent for
      leukocyte identification in whole blood. Fixing samples with formaldehydes
      increases cell permeability and causes surface protein cross-linking that may
      alter staining of both intra- and extracellular markers. The degree of this
      sample alteration by formaldehyde fixation, however, remains in question. In
      addition, little is known about flow cytometry and sample preparation methods in
      mouse whole blood. The purpose of this study was to determine if labeling
      leukocytes with a monoclonal antibody specific to leukocyte common antigen (CD45)
      was superior to labeling with LDS-751 and to determine the effect of sample
      fixation on a mouse whole blood preparation for flow cytometry. Samples were
      incubated with CD16/CD32 Fc receptor blocker, and either 10 microg/ml LDS-751 or
      phosphate buffered saline (PBS). The samples were then fixed with
      paraformaldehyde or diluted with PBS followed by incubation with 5 microg/ml
      PerCP-conjugated anti-CD45, 5 microg/ml FITC-conjugated anti-CD11b, or 80 microM
      dichlorofluorescein diacetate. We found that samples labeled with LDS-751
      demonstrated decreased fluorescence intensity for granulocyte CD11b expression
      and ROS production compared to samples labeled with anti-CD45. In addition,
      sample fixation decreased mean fluorescence intensity in samples labeled with
      either LDS-751 or anti-CD45. We conclude that labeling leukocytes with monoclonal
      antibody CD45 in a mouse whole blood preparation is preferable, as it provides
      improved measurement of leukocyte indices compared to LDS-751. Also, while sample
      fixation prior to antibody staining caused a decrease in overall fluorescence; it
      can be used to successfully identify extra-cellular markers.

PMID- 17187819
TI  - A robust method for production of MHC tetramers with small molecule fluorophores.
AB  - Tetramers of major histocompatibility complex molecules (MHC) are now well
      established reagents for the detection of antigen-specific T cells by flow
      cytometry. MHC tetramers are prepared by mixing enzymatically biotinylated MHC
      molecules with commercial preparations of streptavidin, usually conjugated to a
      fluorescent phycobiliprotein such as phycoerythrin (PE) or allophycocyanin (APC).
      While data obtained with MHC tetramers prepared with small molecule fluorophores
      has been reported, considerable lot-to-lot variation among conventional
      streptavidin conjugates to small molecules prevents routine preparation of such
      reagents. We now report robust preparation of MHC tetramers with small molecule
      fluorophores, using a recombinant mutant of streptavidin incorporating a carboxy
      terminal cysteine in each of the four identical subunits that is conjugated to
      maleimide derivatives of any of several small molecule fluorophores. These
      reagents significantly expand the versatility of the MHC tetramer methodology.

PMID- 17187820
TI  - Seminal fluids mediate sexual inhibition and short copula duration in mated
      female Queensland fruit flies.
AB  - Molecules in male seminal fluid transferred to female insects during mating can
      have potent effects on their subsequent sexual and reproductive behaviour. Like
      many other tephritids, female Queensland fruit flies (Bactrocera tryoni)
      typically have diminished sexual receptivity after their first mating. Also,
      copulations of females that do remate tend to be shorter than those of virgins.
      We here find that virgin females injected with small doses (0.1, 0.2 or 0.5 male
      equivalents) of extracts from the male reproductive tract accessory tissues,
      which consist of male accessory glands, ejaculatory apodeme and ejaculatory duct
      (AG/EA/ED), have diminished receptivity and short copula duration very similar to
      naturally mated females. In contrast, virgin females injected with saline or with
      high doses of AG/EA/ED (1 or 2 male equivalents) that likely exceed the range of
      natural variation retain the higher levels of sexual receptivity and longer
      copulations of un-injected virgins. We conclude that reduced sexual receptivity
      and shorter copulations of mated female Q-flies are mediated by products in the
      male seminal fluid derived from the male reproductive tract accessory tissues.

PMID- 17187821
TI  - In vitro and in vivo effects of bone marrow stem cells on cardiac structure and
      function.
AB  - It is hypothesized that the protection of bone marrow stem cells (BMSCs) on
      ischemic myocardium might be related to the anti-apoptotic effect via paracrine
      mechanisms. In this study, a wide array of cytokines including vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), stromal
      cell-derived factor-1 (SDF-1) and insulin growth factor-1 (IGF-1) were detected
      in the BMSCs cultured medium by ELISA. Myocyte apoptosis was assayed by DNA
      fragmentation and annexin-V staining. Myocardial infarction model was produced by
      ligation of mouse left anterior descending coronary artery (LAD). Before LAD
      ligation, mice were myoablated by irradiation and transplanted with bone marrow
      cells from transgenic mice expressing green fluorescent protein (GFP). After LAD
      ligation, animals were administered stem cell factor (SCF, 200 mug/day/kg, i.p.)
      or saline for 6 days. Animals were sacrificed at 4 weeks after SCF treatment.
      Apoptotic cardiomyocytes were analyzed by TUNEL. Myocardial function was analyzed
      by echocardiography and pressure-volume system. Bcl-2 protein was analyzed by
      Western blotting. Our results showed that cultured BMSCs released VEGF, bFGF, SDF
      1 and IGF-1. Hypoxia-induced cell apoptosis was diminished in cardiomyocytes co
      cultured with BMSCs. Smaller LV dimension and increased LV ejection fraction were
      seen in SCF-treated animals. SCF significantly reduced cardiomyocytes apoptosis
      within peri-infarct area and increased up-regulation expression of Bcl-2 in
      ischemic area. Moreover, conditioned medium from cultured BMSCs also induced up
      regulation of Bcl-2 protein in cardiomyocytes. It is concluded that paracrine
      mediators secreted by BMSCs might be involved in early repair of ischemic heart
      by preventing cardiomyocytes apoptosis and improving cardiac function.

PMID- 17187823
TI  - Conformational stability and domain unfolding of the Von Willebrand factor A
      domains.
AB  - Von Willebrand factor (VWF), a multimeric multidomain glycoprotein secreted into
      the blood from vascular endothelial cells, initiates platelet adhesion at sites
      of vascular injury. This process requires the binding of platelet glycoprotein Ib
      IX-V to the A1 domain of VWF monomeric subunits under fluid shear stress. The A2
      domain of VWF monomers contains a proteolytic site specific for a circulating
      plasma VWF metalloprotease, A Disintegrin and Metalloprotease with Thrombospondin
      motifs, member #13 of the ADAMTS enzyme family (ADAMTS-13), that functions to
      reduce adhesiveness of newly released, unusually large (UL), hyperactive forms of
      VWF. Shear stress assists ADAMTS-13 proteolysis of ULVWF multimers allowing
      ADAMTS-13 cleavage of an exposed peptide bond in the A2 domain. Shear stress may
      induce conformational changes in VWF, and even unfold regions of VWF monomeric
      subunits. We used urea as a surrogate for shear to study denaturation of the
      individual VWF recombinant A domains, A1, A2, and A3, and the domain triplet, A1
      A2-A3. Denaturation was evaluated as a function of the urea concentration, and
      the intrinsic thermodynamic stability of the domains against unfolding was
      determined. The A1 domain unfolded in a 3-state manner through a stable
      intermediate. Domains A2 and A3 unfolded in a 2-state manner from native to
      denatured. The A1-A2-A3 triple domain unfolded in a 6-state manner through four
      partially folded intermediates between the native and denatured states. Urea
      denaturation of A1-A2-A3 was characterized by two major unfolding transitions:
      the first corresponding to the simultaneous complete unfolding of A2 and partial
      unfolding of A1 to the intermediate state; and the second corresponding to the
      complete unfolding of A3 followed by gradual unfolding of the intermediate state
      of A1 at high urea concentration. The A2 domain containing the cleavage site for
      ADAMTS-13 was the least stable of the three domains and was the most susceptible
      to unfolding. The low stability of the A2 domain is likely to be important in
      regulating the exposure of the A2 domain cleavage site in response to shear
      stress, ULVWF platelet adherence, and the attachment of ADAMTS-13 to ULVWF.

PMID- 17187822
TI  - tRNA's wobble decoding of the genome: 40 years of modification.
AB  - The genetic code is degenerate, in that 20 amino acids are encoded by 61 triplet
      codes. In 1966, Francis Crick hypothesized that the cell's limited number of
      tRNAs decoded the genome by recognizing more than one codon. The ambiguity of
      that recognition resided in the third base-pair, giving rise to the Wobble
      Hypothesis. Post-transcriptional modifications at tRNA's wobble position 34,
      especially modifications of uridine 34, enable wobble to occur. The Modified
      Wobble Hypothesis proposed in 1991 that specific modifications of a tRNA wobble
      nucleoside shape the anticodon architecture in such a manner that interactions
      were restricted to the complementary base plus a single wobble pairing for amino
      acids with twofold degenerate codons. However, chemically different modifications
      at position 34 would expand the ability of a tRNA to read three or even four of
      the fourfold degenerate codons. One foundation of Crick's Wobble Hypothesis was
      that a near-constant geometry of canonical base-pairing be maintained in forming
      all three base-pairs between the tRNA anticodon and mRNA codon on the ribosome.
      In accepting an aminoacyl-tRNA, the ribosome requires maintenance of a specific
      geometry for the anticodon-codon base-pairing. However, it is the post
      transcriptional modifications at tRNA wobble position 34 and purine 37, 3'
      adjacent to the anticodon, that pre-structure the anticodon domain to ensure the
      correct codon binding. The modifications create both the architecture and the
      stability needed for decoding through restraints on anticodon stereochemistry and
      conformational space, and through selective hydrogen bonding. A physicochemical
      understanding of modified nucleoside contributions to the tRNA anticodon domain
      architecture and its decoding of the genome has advanced RNA world evolutionary
      theory, the principles of RNA chemistry, and the application of this knowledge to
      the introduction of new amino acids to proteins.

PMID- 17187824
TI  - The sec14 homology module of neurofibromin binds cellular glycerophospholipids:
      mass spectrometry and structure of a lipid complex.
AB  - Neurofibromin is the protein product of the tumor suppressor gene NF1,
      alterations of which are responsible for the pathogenesis of the common disorder
      Neurofibromatosis type I (NF1). The only well-characterized function of
      neurofibromin is its RasGAP activity, contained in the central GAP related domain
      (GRD). By solving the crystal structure of a 31 kDa fragment at the C-terminal
      end of the GRD we have recently identified a novel bipartite lipid-binding module
      composed of a Sec14 homologous and a previously undetected pleckstrin homology
      (PH)-like domain. Using lipid exchange assays along with mass spectrometry we
      show here that the Sec14-like portion binds to 1-(3-sn-phosphatidyl)-sn-glycerol
      (PtdGro), (3-sn-phosphatidyl)-ethanolamine (PtdEtn) and -choline (PtdCho) and to
      a minor extent to (3-sn-phosphatidyl)-l-serine (PtdSer) and 1-(3-sn-phosphatidyl)
      d-myo-inositol (PtdIns). Phosphorylated PtdIns (PtdInsPs) are not detected as
      binders in the mass spectrometry assay, but their soluble inositol-phosphate
      headgroups and related compounds can inhibit the lipid exchange reaction. We also
      present here the crystal structure of this module with the Sec14 portion bound to
      a cellular glycerophospholipid ligand. Our structure has model character for the
      substrate-bound form of yeast Sec14p, of which only detergent bound structures
      are available so far. To assess potential regulation of the lipid exchange
      reaction in detail, we present a novel strategy using nanospray mass
      spectrometry. Ion intensities of initial phospholipids and exchanged deuterated
      analogues bound by the protein module allow the quantitative analysis of
      differences in the exchange activity under various conditions.

PMID- 17187825
TI  - Temporal regulation of viral transcription during development of Thermus
      thermophilus bacteriophage phiYS40.
AB  - Regulation of gene expression of lytic bacteriophage varphiYS40 that infects the
      thermophilic bacterium Thermus thermophilus was investigated and three temporal
      classes of phage genes, early, middle, and late, were revealed. varphiYS40 does
      not encode a (RNAP) and must rely on host RNAP for transcription of its genes.
      Bioinformatic analysis using a model of Thermus promoters predicted 43 putative
      sigma(A)-dependent -10/-35 class phage promoters. A randomly chosen subset of
      those promoters was shown to be functional in vivo and in vitro and to belong to
      the early temporal class. Macroarray analysis, primer extension, and
      bioinformatic predictions identified 36 viral middle and late promoters. These
      promoters have a single common consensus element, which resembles host sigma(A)
      RNAP holoenzyme -10 promoter consensus element sequence. The mechanism
      responsible for the temporal control of the three classes of promoters remains
      unknown, since host sigma(A) RNAP holoenzyme purified from either infected or
      uninfected cells efficiently transcribed all varphiYS40 promoters in vitro.
      Interestingly, our data showed that during infection, there is a significant
      increase and decrease of transcript amounts of host translation initiation
      factors IF2 and IF3, respectively. This finding, together with the fact that most
      middle and late varphiYS40 transcripts were found to be leaderless, suggests that
      the shift to late viral gene expression may also occur at the level of mRNA
      translation.

PMID- 17187826
TI  - AP2 transcription factors regulate expression of CRABPII in hormone responsive
      breast carcinoma.
AB  - BACKGROUND: The AP2 transcription factor family is a set of developmentally
      regulated, retinoic acid (RA) inducible genes, which regulate expression of
      estrogen receptor-alpha (ERalpha) in breast carcinoma. We hypothesized that AP2
      factors regulate a set of genes characteristic of the hormone responsive breast
      cancer phenotype. To better understand the role of AP2 factors in hormone
      responsive breast cancer, we sought to identify AP2-target genes in breast
      epithelial cells. MATERIALS AND METHODS: Overexpression of AP2 factors was
      achieved in human mammary epithelial cells (HMECs) using adenoviral vectors. AP2
      target genes were identified by comparative hybridization to cDNA microarrays
      containing 30,000 human genes. Expression patterns were confirmed by Northern and
      Western blot and by elimination of AP2 using siRNA. Potential regulatory elements
      in promoters of target genes were identified by DNase I hypersensitive site
      mapping. RESULTS: Comparative cDNA microarray hybridization identified a set of
      genes induced by overexpression of AP2alpha and AP2gamma in HMECs. The up
      regulation of cellular retinoic acid-binding protein 2 (CRABPII), EST-1, and ECM1
      was induced by overexpression of AP2alpha, AP2gamma, or a chimeric AP2 factor in
      which the activation domain of AP2alpha was replaced by the activation domain of
      herpesvirus VP16. Interestingly, hormone unresponsive MDA-MB-231 cells were
      resistant to CRABPII induction by any of the AP2 factors. Elimination of AP2gamma
      in MCF7 cells resulted in a significant reduction in CRABPII expression. AP2alpha
      induced DNase I hypersensitive sites in the promoter of the CRABPII gene at -5000
      bp, which corresponds to the site of action of RAR/RXR factors. CONCLUSIONS: AP2
      factors regulate CRABPII expression in HMECs and breast cancer cells and accounts
      for the associated expression of ERalpha and CRABPII in hormone responsive breast
      cancer. Because CRABPII mediates growth suppressive effects of RA in breast
      cancer, the data suggest that AP2 factors have the ability to mediate RA
      responsiveness through the regulation of CRABP II expression.

PMID- 17187827
TI  - Plasma S100beta and NSE levels and progression in multiple sclerosis.
AB  - Plasma levels of the glial cell marker S100beta and the neuronal marker neuron
      specific enolase (NSE) are elevated in various conditions of central nervous
      system damage. In this study we investigated whether plasma levels of S100beta
      and NSE are related to disease progression in multiple sclerosis (MS). Plasma
      levels of S100beta and NSE were measured in 25 patients with relapsing remitting
      MS (RRMS), 23 with secondary progressive MS (SPMS) and 16 with primary
      progressive MS (PPMS). All MS patients were in a clinically stable phase.
      Progression and disability were evaluated during a follow-up period of five
      years. We found that plasma NSE levels were lower in patients with clinically
      relevant worsening on the Expanded Disability Status Scale (EDSS), defined as 1
      point increase from EDSS <6.0 or 0.5 point increase from EDSS> or =6 after five
      years (p=0.042), and in patients with a progressive disease course (p=0.01).
      There was a significant negative correlation between plasma NSE levels and both
      EDSS and Multiple Sclerosis Severity Status (MSSS) scores at baseline and after
      five years of follow-up (r=-0.33 and -0.38, p=0.027 and 0.003). There were no
      significant differences between patient groups in plasma S100beta levels. Plasma
      NSE levels appear inversely related to disease progression in MS.

PMID- 17187828
TI  - Persistent hand spasm: movement disorder or seizure?
AB  - Dystonia is a movement disorder characterized by involuntary, sustained or
      repetitive, patterned muscle contractions or spasms, frequently causing squeezing
      and twisting movements or abnormal postures. Dystonic posturing could be one of
      the accompanying features of epilepsy. We report an elderly lady with intractable
      focal seizure who presented with more than a year of persistent hand spasms. The
      clinical importance of differentiating epilepsy from movement disorders is
      discussed.

PMID- 17187829
TI  - Application of fuzzy-logic models for metabolic control analysis.
AB  - A priori information or valuable qualitative knowledge can be incorporated
      explicitly to describe enzyme kinetics making use of fuzzy-logic models. Although
      restricted to linear relationships, it is shown that fuzzy-logic augmented models
      are not only able to capture non-linear features of enzyme kinetics but also
      allow the proper mathematical treatment of metabolic control analysis. The
      explicit incorporation of valuable qualitative knowledge is crucial, particularly
      when handling data estimated from in vivo kinetics studies, since this
      experimental information is scarce and usually contains measurement errors.
      Therefore, data-driven techniques, such as the one presented in this work, form a
      serious alternative to established kinetics approaches.

PMID- 17187830
TI  - Deviant neurophysiological responses to phonological regularities in speech in
      dyslexic children.
AB  - Developmental dyslexia is strongly associated with a phonological deficit. Yet,
      implicit phonological processing (in)capacities in dyslexia remain relatively
      unexplored. Here we use a neurophysiological response sensitive to experience
      dependent auditory memory traces, the mismatch negativity (MMN), to investigate
      implicit phonological processing of natural speech in dyslexic and normally
      reading children. In a modified passive oddball design that minimizes the
      contribution of acoustic processes, we presented non-words that differed by the
      degree of phonotactic probability, i.e. the distributional frequency of phoneme
      combinations in a given language. Overall morphology of ERP responses to the non
      words indicated comparable processing of acoustic-phonetic stimulus differences
      in both children groups. Consistent with previous findings in adults, normally
      reading children showed a significantly stronger MMN response to the non-word
      with high phonotactic probability (notsel) as compared to the non-word with low
      phonotactic probability (notkel), suggesting auditory cortical tuning to
      statistical regularities of phoneme combinations. In contrast, dyslexic children
      did not show this sensitivity to phonotactic probability. These findings indicate
      that the phonological problems often reported in dyslexia relate to a subtle
      deficit in the implicit phonetic-phonological processing of natural speech.

PMID- 17187832
TI  - Variation of glucosinolates in vegetable crops of Brassica rapa.
AB  - Glucosinolate levels in leaves were determined in a collection of 113 varieties
      of turnip greens (Brassica rapa L.) from northwestern Spain grown at two sites.
      Sensorial attributes were also assessed by a consumer panel. The objectives were
      to determine the diversity among varieties in total glucosinolate content and
      glucosinolate profile and to evaluate their sensory attributes in relation to
      glucosinolate content for breeding purposes. Sixteen glucosinolates were
      identified, being the aliphatic glucosinolates, gluconapin and glucobrassicanapin
      the most abundant. Other aliphatic glucosinolates, such as progoitrin,
      glucoalyssin, and gluconapoleiferin were relatively abundant in varieties with a
      different glucosinolate profile. Indolic and aromatic glucosinolate
      concentrations were low and showed few differences among varieties. Differences
      in total glucosinolate content, glucosinolate profile and bitterness were found
      among varieties, with a total glucosinolate content ranging from 11.8 to
      74.0micromolg(-1) dw at one site and from 7.5 to 56.9micromolg(-1) dw at the
      other site. Sensory analysis comparing bitterness with variation in
      glucosinolate, gluconapin and glucobrassicanapin concentrations suggested that
      these compounds and their breakdown products are not the only determinants of the
      characteristic flavour of this vegetable. Other phytochemicals are probably
      involved on the characteristic bitter flavour. The varieties MBG-BRS0132, MBG
      BRS0082, MBG-BRS0173, and MBG-BRS0184 could be good candidates for future
      breeding programs since they had high total glucosinolate content and good
      agronomic performance. The presence of glucoraphanin in some varieties should be
      studied more extensively, because this aliphatic glucosinolate is the precursor
      of sulforaphane, a potent anti-cancer isothiocyanate.

PMID- 17187831
TI  - Rapid neuroendocrine responses evoked at the onset of social challenge.
AB  - At the onset of agonistic social challenge, individuals must assess the degree of
      threat the opponent represents in order to react appropriately. We aimed to
      characterize the neuroendocrine changes accompanying this period of initial
      social assessment using the lizard Anolis carolinensis. Conveyance of aggressive
      intent by male A. carolinensis is facilitated by rapid postorbital skin darkening
      (eyespot), whereas eyespot presence inhibits opponent aggression. By manipulating
      this visual signal, we also investigated whether differing neuroendocrine changes
      were evoked by initial presentation of varying levels of social threat. Subjects
      were painted postorbitally either with black paint (high threat level), green
      paint (low threat level) or water (controls). Painted animals were presented with
      a mirror and sampled immediately upon exhibiting aggressive intent towards the
      reflected simulated opponent, but before producing behaviors such as motor
      pattern-based displays. Control animals (blank surface presented) were sampled at
      times derived from averaging response times of painted subjects. Brains and
      plasma were analyzed for monoamine activity and catecholamine levels using
      electrochemical HPLC. Social threat evoked increases in plasma catecholamine
      levels indistinguishable from those caused by brief environmental disturbance.
      However, brief social challenge caused distinct rapid increases in amygdala and
      nucleus accumbens (NAc) dopamine and serotonin levels. Amygdalar changes were
      associated with general social threat presence, but NAc monoamines were affected
      by both threat level and subject motivation to engage in confrontation. This
      suggests that specific rapid activity changes in key forebrain limbic nuclei
      differ according to the degree of social threat perceived at the start of the
      interaction.

PMID- 17187833
TI  - Geraniol synthases from perilla and their taxonomical significance.
AB  - Geraniol synthases were isolated from five pure strains of Perilla citriodora and
      Perilla frutescens which vary in essential oil type, the main compounds of which
      were citral, elsholtziaketone, perillaketone, and perillene, respectively. This
      result supports the putative biosynthetic pathways of these three furylalkenes
      which are all produced by way of citral. Nucleotide sequences of geraniol
      synthases from three oil types of P. citriodora were identical, and almost the
      same as the sequence from P. frutescens, a species with twice the chromosome
      number of P. citriodora. This identity in sequence between P. citriodora and P.
      frutescens, together with other previous results, indicates that P. frutescens
      was formed as an amphidiploid of P. citriodora and an unknown wild species.

PMID- 17187834
TI  - Peroxidase activity can dictate the in vitro lignin dehydrogenative polymer
      structure.
AB  - The objective of this study was to assess the influence of the
      peroxidase/coniferyl alcohol (CA) ratio on the dehydrogenation polymer (DHP)
      synthesis. The soluble and unsoluble fractions of horseradish peroxidase (HRP)
      catalyzed CA dehydrogenation mixtures were recovered in various proportions,
      depending on the polymerization mode (Zutropf ZT/Zulauf ZL) and HRP/CA ratio (1.6
      1100purpurogallin U mmol(-1)). The ZL mode yielded 0-57%/initial CA of unsoluble
      condensed DHPs (thioacidolysis yields <200micromolg(-1)) with a proportion of
      uncondensed CA end groups increasing with the HRP/CA ratio (7.2-55.5%/total
      uncondensed CA). Systematically lower polymer yields (0-49%/initial CA) were
      obtained for the ZT mode. In that mode, a negative correlation was established
      between the beta-O-4 content (thioacidolysis yields: 222-660micromolg(-1)) and
      the HRP/CA ratio. In both modes, decreasing the HRP/CA ratio below 18Ummol(-1)
      favoured an end-wise polymerization process evidenced by the occurrence of tri-,
      tetra- and pentamers involving at least one beta-O-4 bond. At low ratio, the
      unsoluble ZT DHP was found to better approximate natural lignins than DHPs
      previously synthesized with traditional methods. Besides its possible implication
      in lignin biosynthesis, peroxidase activity is a crucial parameter accounting for
      the structural variations of in vitro DHPs.

PMID- 17187835
TI  - Goats may experience reproductive failures and shed Coxiella burnetii at two
      successive parturitions after a Q fever infection.
AB  - Q fever is a zoonosis caused by the obligate intracellular bacterium, Coxiella
      burnetii. Aborting domestic ruminants are the main source of human infection. In
      January 2003, an abortion episode occurred in a dairy caprine herd where 18/60
      (30%) goats experienced reproductive problems: 4/60 (7%) aborted and 14/60 (23%)
      had stillbirths. Serological screening for abortion-related infectious diseases
      suggested Q fever. The diagnosis of C. burnetii infection was confirmed with PCR
      based on the occurrence of C. burnetii shedding into vaginal mucus, faeces and
      colostrums taken after kidding from the affected animals. The pregnancy following
      this episode resulted in one abortion and four stillbirths; three of those goats
      had already experienced reproductive failure during the previous kidding season.
      The seroprevalence of C. burnetii infection and the bacteria shedding were
      investigated using both ELISA and PCR assays, respectively, during the course of
      the initial and subsequent kidding seasons. Serological testing, performed on the
      whole herd 6 weeks after the abortion episode, showed 48/60 (80%) of ELISA
      positive goats. PCR assay performed on both vaginal swab and milk samples showed
      that the bacterium was shed for almost four months after the outbreak. C.
      burnetii DNA was also amplified from vaginal swab and milk samples taken from
      goats after the second kidding season. Furthermore, the bacteria were found into
      14 vaginal swabs and 12 milk samples taken from infected females at both kidding
      seasons.

PMID- 17187836
TI  - Effects of oral supplementation with bovine colostrum on the immune system of
      weaned piglets.
AB  - The aim of this study was to evaluate the influence of bovine colostrum
      supplementation on the immune system of weaned piglets in a context of a full ban
      of in-feed antibiotics. After weaning at 21 days, 24 outbred piglets were fed
      with a diet supplemented daily for three weeks with 0, 1 or 5 g of colostrum.
      Feed intake, growth performance, haematological parameters, and serum and local
      anti-colostrum immunoglobulin levels were examined. Lymphocytes from the blood,
      spleen, and gut-associated lymphoid were analysed for phenotype as well as for
      their ability to produce cytokines. The stimulation index (SI) of mononuclear
      cells from different organs was obtained after colostral or mitogenic
      stimulation. Feed intake, growth, and haematological parameters were not
      significantly affected by colostrum. Total serum IgA levels were increased after
      colostrum supplementation, with a transient decrease in total IgG. Local anti
      colostrum immunization was observed in colostrum-fed piglets. The CD21+/CD3+
      cells populations of the ileal Peyer's patch (iPP) were markedly affected. The SI
      of lymphocyte populations changed significantly whereas, naive blood lymphocytes
      were not stimulated in vitro in the presence of bovine colostrum, suggesting
      local anti-colostrum immunization and an absence of direct mitogenic effects of
      the colostrum. Both Th1 and Th2 cytokine production was present in the different
      organs of colostrum-fed piglets. Bovine colostrum especially stimulated iPP
      cells.

PMID- 17187837
TI  - Calcium uptake and membrane trafficking in response to PTH or 25(OH)D3 in
      polarized intestinal epithelial cells.
AB  - Cell culture techniques providing retention of the polarized enterocyte
      morphology has allowed, for the first time, comparison of parathyroid hormone
      (PTH)- and 25-hydroxyvitamin D(3) [25(OH)D(3)]-induced (45)Ca uptake with
      membrane trafficking events discerned using confocal microscopy. Treatment of
      cells with 65 pM bPTH(1-34) promoted enhanced (45)Ca uptake between 1 and 10 min
      after peptide. The protein kinase A (PKA) antagonist, RpcAMP inhibited hormone
      mediated uptake. At the microscopic level, cells labeled with the endocytic
      tracking dye FM1-43 revealed increased punctate staining 50-550s after hormone.
      Pretreatment of cells with RpcAMP abolished this pattern of staining. The calcium
      indicator dye fluo-3 AM revealed faint punctate labeling in controls, with
      increased bands of punctate labeling in the apical region of the cells after
      peptide hormone, and ultimately the basal region. Parallel studies conducted with
      the metabolite 25(OH)D(3) resulted in a slower stimulation of (45)Ca uptake 5-10
      min after steroid, which was also inhibited by preincubation with RpcAMP. Cells
      labeled with FM1-43 and then treated with steroid showed no change in
      distribution of fluorescence during the 10 min incubation period. Confocal
      microscopy with fluo-3 revealed intense apical fluorescence--that after steroid -
      streamed to a perinuclear position, and ultimately the basal area. Uniformly
      diffuse staining, which would indicate cytoplasmic calcium transport, was
      observed only in controls. Membrane trafficking and compartmentalized calcium
      appear to be integral to agonist mediated cation transport.

PMID- 17187838
TI  - Accumulation of microcystins in various organs of the freshwater snail Sinotaia
      histrica and three fishes in a temperate lake, the eutrophic Lake Suwa, Japan.
AB  - So far, there has been only one study to examine microcystin (MC) contents in
      various organs of snails in a subtropical Chinese lake. In this study, tissue
      distribution and seasonal dynamics of MC-RR and -LR were investigated in various
      organs of a freshwater snail (Sinotaia histrica) in a temperate eutrophic lake,
      Lake Suwa, Japan. Accumulation of microcystins in some fish was also
      investigated. There was marked temporal variation in the MC content of various
      organs of the snail. The digestive tract had the highest MC content (mean 9.03
      microg g(-1) DW and range 3.74-23.2 microg g(-1) DW), followed by the gonad (mean
      6.90 microg g(-1) DW and range 0.07-22.7 microg g(-1) DW) and hepatopancreas
      (mean 5.38 microg g(-1) DW and range 1.08-8.79 microg g(-1) DW), whereas the foot
      had the least (mean 2.48 microg g(-1) DW and range 0.04-4.45 microg g(-1) DW).
      The disappearance of MC-LR in the hepatopancreas indicated that S. histrica is
      able to depurate MC-LR efficiently. MC-RR was detected in the muscle of three
      species of fish, with the highest content in Carassius auratus (79.4 microg kg(
      1) BW). Because of substantial MC accumulation in these edible aquatic animals in
      Lake Suwa, it is recommended that regular monitoring of MCs should be undertaken
      in both cyanobacteria and aquatic animals.

PMID- 17187839
TI  - Vergence accommodation and monocular closed loop blur accommodation have similar
      dynamic characteristics.
AB  - Retinal blur and disparity are two different sensory signals known to cause a
      change in accommodative response. These inputs have differing neurological
      correlates that feed into a final common pathway. The purpose of this study was
      to investigate the dynamic properties of monocular blur driven accommodation and
      binocular disparity driven vergence-accommodation (VA) in human subjects. The
      results show that when response amplitudes are matched, blur accommodation and VA
      share similar dynamic properties.

PMID- 17187840
TI  - Perceived direction of plaid motion is not predicted by component speeds.
AB  - It has been shown that the perceived direction of a plaid with components of
      unequal contrast is biased towards the direction of the higher-contrast component
      [Stone, L. S., Watson, A. B., & Mulligan, J. B. (1990). Effect of contrast on the
      perceived direction of a moving plaid. Vision Research 30, 1049-1067]. It was
      proposed that this effect is due to the influence of contrast on the perceived
      speed of the plaid components. This led to the conclusion that perceived plaid
      direction is computed by the intersection of constraints (IOC) of the perceived
      speed of the components rather than their physical speeds. We tested this
      proposal at a wider range of component speeds (2-16deg/s) than used previously,
      across which the effect of contrast on perceived speed is seen to reverse. We
      find that across this range, perceived plaid direction cannot be predicted either
      by a model which takes the IOC of physical or perceived component speed. Our
      results are consistent with an explanation of 2D motion perception proposed by
      [Bowns, L. (1996). Evidence for a feature tracking explanation of why Type II
      plaids move in the vector sum direction at short durations. Vision Research, 36,
      3685-3694.] in which the motion of the zero-crossing edges of the features in the
      stimulus contribute to the perceived direction of motion.

PMID- 17187841
TI  - Environmental risk assessment of antibiotics in the Swedish environment with
      emphasis on sewage treatment plants.
AB  - The potential risks associated with antibiotics present in the Swedish
      environment were assessed using concentrations found in hospital effluent, and
      sewage treatment waters and sludge, in combination with data on their
      environmental effects obtained from the literature. For the aqueous environment,
      measured environmental concentrations and effect/no observed effect concentration
      ratios were much lower than one in most cases. The only exceptions, where
      concentrations of the investigated substances were high enough to pose potential
      risks, were the concentrations of the two fluoroquinolones, ofloxacin and
      ciprofloxacin, in the hospital effluent. Treating digested dewatered sludge by
      heat did not fully eliminate norfloxacin or ciprofloxacin, thus pellets may still
      contain high amounts of these substances (sub to low mgkg(-1)dw). In leaching
      tests less than 1% of the amounts of these fluoroquinolones in the sludge or
      pellets reached the aqueous phase, indicating that their mobility is limited if
      sludge is used to fertilize soil.

PMID- 17187842
TI  - Composition of a protein-like fluorophore of dissolved organic matter in coastal
      wetland and estuarine ecosystems.
AB  - This study demonstrates the compositional heterogeneity of a protein-like
      fluorescence emission signal (T-peak; excitation/emission maximum at 280/325 nm)
      of dissolved organic matter (DOM) samples collected from subtropical river and
      estuarine environments. Natural water samples were collected from the Florida
      Coastal Everglades ecosystem. The samples were ultrafiltered and excitation
      emission fluorescence matrices were obtained. The T-peak intensity correlated
      positively with N concentration of the ultrafiltered DOM solution (UDON),
      although, the low correlation coefficient (r(2)=0.140, p<0.05) suggested the
      coexistence of proteins with other classes of compounds in the T-peak. As such,
      the T-peak was unbundled on size exclusion chromatography. The elution curves
      showed that the T-peak was composed of two compounds with distinct molecular
      weights (MW) with nominal MWs of about >5 x 10(4) (T(1)) and approximately 7.6 x
      10(3) (T(2)) and with varying relative abundance among samples. The T(1)-peak
      intensity correlated strongly with [UDON] (r(2)=0.516, p<0.001), while T(2)-peak
      did not, which suggested that the T-peak is composed of a mixture of compounds
      with different chemical structures and ecological roles, namely proteinaceous
      materials and presumably phenolic moieties in humic-like substances. Natural
      source of the latter may include polyphenols leached from senescent plant
      materials, which are important precursors of humic substances. This idea is
      supported by the fact that polyphenols, such as gallic acid, an important
      constituent of hydrolysable tannins, and condensed tannins extracted from red
      mangrove (Rhizophora mangle) leaves exhibited the fluorescence peak in the close
      vicinity of the T-peak (260/346 and 275/313 nm, respectively). Based on this
      study the application of the T-peak as a proxy for [DON] in natural waters may
      have limitations in coastal zones with significant terrestrial DOM input.

PMID- 17187843
TI  - Effects of chitosan on oxidative stress and metallothioneins in aquatic worm
      Tubifex tubifex (Oligochaeta, Tubificidae).
AB  - Chitosan is a natural polymer which has the property to elicit the natural
      defenses mechanism in plant and which can be an interesting biopesticides. It is
      then necessary to investigate the potential toxicity of chitosan for aquatic
      animal health. Metallothioneins (MTs) are low molecular weight proteins, mainly
      implicated in metal ion detoxification. Increase in MTs contents had been
      considered as a specific biomarker of metal exposure. However recently it has
      been demonstrated that MTs participate in several cellular functions such as
      regulation of growth and anti-oxidative defenses. Therefore, the induction of MTs
      has been investigated in the aquatic worms Tubifex tubifex exposed to chitosan.
      MTs levels in exposed worm increased significantly (p > 0.05) after 2, 4, and 7
      days of exposure to different concentrations of chitosan (maximum + 158.19 +/-
      10.2% after 2 days of exposure to 125 mgl(-1) of chitosan). Several antioxidant
      parameters including glutathione (GSH), glutathione-S-transferase (GST),
      glutathione reductase (GR), and catalase (CAT) were quantified in T. tubifex
      after 2, 4, and 7 days of exposure to chitosan. Exposure to chitosan had a
      negative effect on T. tubifex growth (maximum effect -6.11 +/- 1.6% after 7 days
      with 125 mgl(-1)) demonstrating the toxic effect of the pesticide. This growth
      rate decrease was accompanied by a reduction in protein contents. The activity of
      catalase (CAT), glutathione-S-transferase (GST), and glutathione reductase (GR)
      increased in response to the chitosan demonstrating an oxidative stress in the
      worms.

PMID- 17187844
TI  - Arsenic extractability in soils in the areas of former arsenic mining and
      smelting, SW Poland.
AB  - Arsenic (As) concentrations in soils and waste material in two areas of former As
      mining and processing: Zloty Stok (Zlote Mts.) and Zelezniak (Kaczawskie Mts.),
      SW Poland, were measured to assess levels and environmental risk associated with
      possible increases in arsenic mobility under changing pH and redox conditions.
      Twenty six soil samples were collected from 12 sites, and represented a broad
      spectrum of soil properties and parent material origin, including natural soils,
      mine spoils, slags and tailings. Arsenic species were examined using a sequential
      extraction technique. The changes in As solubility were determined from
      extraction test solutions adjusted to solution pH values varying from 2 to 8. The
      effects of reducing conditions on As mobility were examined in incubation tests.
      Most of soils demonstrated extremely high concentrations of As, both of natural
      and anthropogenic origin. Total As concentrations in all samples were in the
      range 100-43,500 mg/kg. Sequential extraction techniques suggested that the main
      species of As in all soils were those bound to iron (Fe) oxides, in particular
      amorphous ones, whereas the contributions of mobile and specifically sorbed As
      forms were relatively low. In tailings and tailings-affected alluvial soils, As
      occurred mainly in residual forms, however these soils also had considerable
      amounts of mobile As. In all other soils, mobile As forms were very low. Arsenic
      mobilization could be possible at extremely low or high pH conditions (pH<2 or
      pH>8), and this may be of particular practical importance in the case of
      tailings, which are highly alkaline. High pH promotes solubilization of As forms
      in reducing conditions, whereas in neutral and acidic soils the risk of As
      release under reducing conditions is limited.

PMID- 17187845
TI  - Radiostrontium uptake by plants from different soil types in Kazakhstan.
AB  - The transfer of 90Sr to a range of different plant species grown on a range of
      different soil types in Kazakhstan, including three from the Semipalatinsk Test
      Site (STS), has been measured in a lysimeter experiment. 90Sr uptake by Stipa spp
      was significantly higher than for other vegetation species. The uptake of 90Sr
      from chernozem was significantly lower than that from the other soil types which
      is consistent with other literature. There was a significant negative
      relationship between 90Sr uptake and calcium, humus and CEC concentration in the
      soil for Agropyrum spp, Artemisia spp but not for Stipa spp or Bromus spp. The
      transfer to vegetation from soil has been quantified using the aggregated
      transfer coefficients for each species. Tag values range from 0.6 to 11.9 m2 kg
      1x10(-3) over all measurements. The transfer of 90Sr to plants from the Kazakh
      soils was low compared to previously reported data and to that given from
      literature reviews.

PMID- 17187846
TI  - Rainfall intensity and phosphorus source effects on phosphorus transport in
      surface runoff from soil trays.
AB  - Phosphorus runoff from agricultural fields amended with mineral fertilizers and
      manures has been linked to freshwater eutrophication. A rainfall simulation study
      was conducted to evaluate the effects of different rainfall intensities and P
      sources differing in water soluble P (WSP) concentration on P transport in runoff
      from soil trays packed with a Berks loam and grassed with annual ryegrass (Lolium
      multiflorum Lam.). Triple superphosphate (TSP; 79% WSP), low-grade super single
      phosphate (LGSSP; 50% WSP), North Carolina rock phosphate (NCRP; 0.5% WSP) and
      swine manure (SM; 70% WSP), were broadcast (100 kg total P ha-1) and rainfall
      applied at 25, 50 and 75 mm h-1 1, 7, 21, and 56 days after P source application.
      The concentration of dissolved reactive (DRP), particulate (PP), and total P (TP)
      was significantly (P<0.01) greater in runoff with a rainfall intensity of 75 than
      25 mm h-1 for all P sources. Further, runoff DRP increased as P source WSP
      increased, with runoff from a 50 mm h-1 rain 1 day after source application
      having a DRP concentration of 0.25 mg L-1 for NCRP and 28.21 mg L-1 for TSP. In
      contrast, the proportion of runoff TP as PP was greater with low (39% PP for
      NCRP) than high WSP sources (4% PP for TSP) averaged for all rainfall
      intensities. The increased PP transport is attributed to the detachment and
      transport of undissolved P source particles during runoff. These results show
      that P source water solubility and rainfall intensity can influence P transport
      in runoff, which is important in evaluating the long-term risks of P source
      application on P transport in surface runoff.

PMID- 17187847
TI  - The use of adjuvant radiation therapy in early endometrial cancer by members of
      the Society of Gynecologic Oncologists in 2005.
AB  - OBJECTIVES: To determine current patterns of care for early stage endometrial
      cancer by the members of the Society of Gynecologic Oncologists (SGO). METHODS: A
      survey detailing the use of adjuvant radiation in early stage endometrial cancer
      was conducted. Details of surgery, indications for staging, and use of adjuvant
      radiation for cases primarily seen by the respondent and for those cases referred
      postoperatively without staging information were collected and compared to a
      similar survey from 1999. RESULTS: The practice demographics of the respondents
      are similar to the 1999 survey. SGO members are now more likely to perform
      complete surgical staging during all surgeries for endometrial cancer than in
      1999 (71% vs. 48%; P<0.0001). A higher percentage of respondents now describe
      surgery as a complete lymphadenectomy (76% vs. 44%: P<0.0001) and believe this is
      therapeutic (71% vs. 66%: P=0.04). Approximately half of SGO members now use
      laparoscopic assisted staging in the primary treatment of endometrial cancer.
      Since 1999, there is a significant decrease in the recommendation for
      postoperative RT. In almost all cases where RT is recommended, the use of vaginal
      RT is now more common than pelvic RT. In all situations, consult recommendations
      for additional intervention were more likely if complete surgical staging had not
      been performed, suggesting that all patients with endometrial cancer would
      benefit from surgery by a gynecologic oncologist. CONCLUSIONS: There is an
      increase in complete surgical staging of endometrial cancer, an increase in the
      use of laparoscopy, and a marked decrease in the use of pelvic RT since 1999.

PMID- 17187848
TI  - Transperitoneal laparoscopic staging with aortic and pelvic lymph node dissection
      for gynecologic malignancies.

PMID- 17187850
TI  - Sublingual immunotherapy.

PMID- 17187852
TI  - Modest effects of a controlled worksite environmental intervention on
      cardiovascular risk in office workers.
AB  - OBJECTIVE: To present the effects of a relatively modest environmental
      intervention on biological cardiovascular risk indicators. METHOD: A controlled
      trial, including two worksites. Measurements (i.e., body composition, blood
      pressure and serum cholesterol) took place at baseline and at 3- and 12-month
      follow-up. The 12-month environmental intervention (The Hague, The Netherlands,
      2004) consisted of: a 'Food'-part: to stimulate healthier food choices by means
      of product information in the canteen, and a 'Steps'-part: focused on stimulating
      stair use by means of motivational prompts in staircases and on elevator doors.
      RESULTS: Significant differences in change between groups (n=540) in favor of the
      intervention group were found on: [1] total cholesterol for women (-0.35 mmol/l);
      [2] HDL for men at 3 months (0.05 mmol/l) and 12 months (0.10 mmol/l); and [3]
      the total-HDL ratio for the total intervention group at 3 and 12 months (-0.45
      mmol/l). Both groups showed a decrease in all body composition values at both
      follow-ups. A significant difference in change in systolic BP was found in favor
      of the control group (approximately 4 mm Hg), due to an increase in the
      intervention group at both follow-ups. CONCLUSIONS: Based on the contrasting
      results, this modest environmental intervention was ineffective in reducing
      cardiovascular risk in a population of office workers.

PMID- 17187851
TI  - Ambient particulate matter directs nonclassic dendritic cell activation and a
      mixed TH1/TH2-like cytokine response by naive CD4+ T cells.
AB  - BACKGROUND: Dendritic cells (DCs) translate environmental cues into T-cell
      activating signals, and are centrally involved in allergic airway inflammation.
      Ambient particulate matter (APM) is ubiquitous and associated with allergic
      diseases, but it is unknown whether APM directly activates DCs. OBJECTIVE: To
      study comprehensively the effects of APM on myeloid DC phenotype and function.
      METHODS: Development of DC was modeled using human CD34(+) progenitor cells. APM
      was collected from ambient outdoor air in Baltimore city. We studied the effects
      of APM on DC activation in vitro, compared with LPS. RESULTS: Ambient particulate
      matter enhanced DC expression of costimulatory receptors but suppressed the
      expression of both the endocytosis receptor CD206 and uptake of fluorescein
      isothiocyanate-conjugated dextran. The expression of the Toll-like pattern
      recognition receptors Toll-like receptor 2 and Toll-like receptor 4 was also
      blunted. APM-exposed DCs secreted less IL-12 and IL-6 but exhibited increased
      secretion of IL-18 and IL-10 compared with LPS stimulation. A T(H)2-like pattern
      of cytokine production was seen in cocultures of APM-stimulated DCs and
      alloreactive naive CD4(+) T cells where the IL-13 to IFN-gamma ratio was
      reversed. This contrasted with the T(H)1 polarizing effects of LPS on DCs.
      CONCLUSION: We report for the first time that APM-exposed DCs direct a complex
      T(H)1/T(H)2-like pattern of T-cell activation by mechanisms that involve
      nonclassic activation of DCs. CLINICAL IMPLICATIONS: Inhaled APM can act directly
      on DCs as a danger signal to direct a proallergic pattern of innate immune
      activation.

PMID- 17187853
TI  - Brief report: methods for collecting sexual behaviour information from South
      African adolescents--a comparison of paper versus personal digital assistant
      questionnaires.
AB  - Reporting bias in adolescent behavioural research may be overcome with the use of
      personal digital assistants (PDA) or other computer based technologies. However,
      there is little insight into the use of these tools among adolescents in low
      resource settings. We compared self-administered paper questionnaires with PDA
      questionnaires to collect sexual behaviour data from a sample of 11-19 year olds
      living in a periurban, Xhosa-speaking community in South Africa. There was a high
      level of agreement between sexual risk behaviour data collected via each method
      (kappas> or = 0.50). Data collected from the PDA questionnaires were more
      complete. Subjectively, adolescents found the use of PDA to be simple and
      confidential. PDA may be a useful method to collect sensitive, self-reported
      information from adolescents in resource-limited settings.

PMID- 17187855
TI  - Morphological constraints on calcium dependent glutamate receptor trafficking
      into individual dendritic spine.
AB  - Glutamate receptor trafficking into dendritic spines is a pivotal step in
      synaptic plasticity, yet the relevance of plasticity-producing rise of [Ca2+]i
      and of spine morphology to subsequent delivery of glutamate receptors into
      dendritic spine heads are still not well understood. Following chemical induction
      of LTP, an increase in eGFP-GluR1 fluorescence in short but not long dendritic
      spines of cultured hippocampal neurons was found. Repeated flash photolysis of
      caged calcium, which produced a transient rise of [Ca2+]i inside spine heads
      caused a selective, actin and protein synthesis dependent increase of eGFP-GluR1
      in these spines. Strikingly, GluR1 increase was correlated with the ability of a
      calcium transient generated in the spine head to diffuse into the parent
      dendrite, and inversely correlated with the length of the spine: short spines
      were more likely to raise GluR1 than long ones. These observations link, for the
      first time, calcium transients in dendritic spines with spine morphology and its
      ability to undergo synaptic plasticity.

PMID- 17187854
TI  - Polysaccharide intercellular adhesin or protein factors in biofilm accumulation
      of Staphylococcus epidermidis and Staphylococcus aureus isolated from prosthetic
      hip and knee joint infections.
AB  - Nosocomial staphylococcal foreign-body infections related to biofilm formation
      are a serious threat, demanding new therapeutic and preventive strategies. As the
      use of biofilm-associated factors as vaccines is critically restricted by their
      prevalence in natural staphylococcal populations we studied the distribution of
      genes involved in biofilm formation, the biofilm phenotype and production of
      polysaccharide intercellular adhesin (PIA) in clonally independent Staphylococcus
      aureus and Staphylococcus epidermidis strains isolated from prosthetic joint
      infections after total hip or total knee arthroplasty. Biofilm formation was
      detected in all S. aureus and 69.2% of S. epidermidis strains. Importantly, 27%
      of biofilm-positive S. epidermidis produced PIA-independent biofilms, in part
      mediated by the accumulation associated protein (Aap). Protein-dependent biofilms
      were exclusively found in S. epidermidis strains from total hip arthroplasty
      (THA). In S. aureus PIA and proteins act cooperatively in biofilm formation
      regardless of the infection site. PIA and protein factors like Aap are of
      differential importance for the pathogenesis of S. epidermidis in prosthetic
      joint infections (PJI) after THA and total knee arthroplasty (TKA), implicating
      that icaADBC cannot serve as a general virulence marker in this species. In S.
      aureus biofilm formation proteins are of overall importance and future work
      should focus on the identification of functionally active molecules.

PMID- 17187856
TI  - N-Benzyladriamycin-14-valerate (AD 198) cytotoxicty circumvents Bcr-Abl anti
      apoptotic signaling in human leukemia cells and also potentiates imatinib
      cytotoxicity.
AB  - Bcr-Abl activity in chronic myelogenous leukemia (CML) results in dysregulated
      cell proliferation and resistance against multiple cytotoxic agents due to the
      constitutive activation of proliferative signaling pathways. Currently, the most
      effective treatment of CML is the inhibition of Bcr-Abl activity by imatinib
      mesylate (Gleevec). Imatinib efficacy is limited by development of resistance
      through either expression of Bcr-Abl variants that bind imatinib less avidly,
      increased expression of Bcr-Abl, or expression of multidrug transport proteins. N
      Benzyladriamycin-14-valerate (AD 198) is a novel antitumor PKC activating agent
      that triggers rapid apoptosis through PKC-delta activation and mitochondrial
      depolarization in a manner that is unaffected by Bcl-2 expression. We demonstrate
      that Bcr-Abl expression does not confer resistance to AD 198. Further, AD 198
      rapidly induces Erk1/2 and STAT5 phosphorylation prior to cytochrome c release
      from mitochondria, indicating that proliferative pathways are active even as drug
      treated cells undergo apoptosis. At sub-cytotoxic doses, AD 198 and its cellular
      metabolite, N-benzyladriamycin (AD 288) sensitize CML cells to imatinib through a
      supra-additive reduction in the level of Bcr-Abl protein expression. These
      results suggest that AD 198 is an effective treatment for CML both in combination
      with imatinib and alone against imatinib-resistant CML cells.

PMID- 17187857
TI  - Release and leaching of plant DNA in unsaturated soil column.
AB  - Little information is available on the process of DNA release from plants and
      neither is there much information to be found regarding DNA transport in the
      vadose zone. Unsaturated soil columns were used to examine the release and
      transport of DNA content in the leaf of tomato variety Palmiro, which was
      introduced into the soil columns after being dried at 35 degrees C for 3 days.
      Soil columns were leached with sterile water at a rate of 0.5mLh(-1) for 104
      days. DNA from column leachate water was extracted and analysed. Both
      quantitative and qualitative measurements of extracted DNA were taken. Tomato
      gene sequences were detected using PCR amplification based on tomato specific 18S
      primers. The concentration of total DNA in soil column leachate water ranged from
      6.7 to 50.4microgL(-1). Genomic analysis using agarose gel electrophoresis showed
      degradation of DNA after its passage through unsaturated soil columns. The
      presence of tomato genes in the leachate water of soil columns suggests a
      potential release of tomato DNA from leaves and potential transport of DNA over
      considerable distances in water-unsaturated soil. Consequently, transport of
      plant DNA in vadose zone is indicated, and there is a risk that the DNA may reach
      the groundwater.

PMID- 17187858
TI  - Phototactic behavior in Daphnia magna Straus as an indicator of toxicants in the
      aquatic environment.
AB  - In this study, the phototactic behavior of Daphnia magna was investigated as a
      possible bioindicator for the following 11 chemicals commonly found in the
      aquatic environment: benzo(b)fluoranthene, mercury (II) chloride, dimethoate,
      lindane, linuron, MCPA, TBTO, carbon tetrachloride, thiram, 2,4,6-trichlorophenol
      and arsenic trioxide. Phototactic response was monitored as the movement of 7 to
      8 day-old D. magna individuals. The analysis was carried out using glass test
      tubes divided radially into two zones, with increasing distance from a light
      source. For each of the compounds, different concentrations and exposure times
      were analyzed, and the behavior of the D. magna in each of the treatments
      compared to the controls in which the chemicals were not added. Using the
      experimental model described here, all of the 11 chemicals could be detected
      following exposure times of between 15 min and 48 h. The lowest concentrations
      detected using this technique were between 2 and 43 times lower than the LC(50)
      and EC(50) values reported for D. magna. The results of this study show that the
      analysis of phototactism is a useful method for detecting the presence of a wide
      range of potentially toxic chemicals found in the aquatic environment.

PMID- 17187859
TI  - High frequency deep brain stimulation: what are the therapeutic mechanisms?
AB  - High frequency deep brain stimulation (HFS) used to treat the symptoms of
      Parkinson's disease (PD) was first assumed to act by reducing an excessive tonic
      GABAergic inhibitory output from the internal globus pallidus (GPi). Stimulation
      in GPi might produce this directly by mechanisms such as depolarization block or
      activation of presynaptic inhibitory fibers, and the same mechanisms evoked by
      HFS in the subthalamic nucleus (STN) could reduce the excitatory action of STN on
      GPi neurons. Although somatic recordings from neurons near the stimulation site
      may appear to support this potential mechanism, the action downstream from the
      site of stimulation often is not consistent with this interpretation. A more
      parsimonious explanation for the similar effects of HFS in STN or GPi and a
      lesion of either of these structures is that both HFS and pallidotomy interrupt
      an abnormal pattern of firing in cortico-basal ganglia-thalamocortical loops that
      is responsible for the symptoms of PD.

PMID- 17187860
TI  - Physico-chemical and toxicological characterization of the historic estuarine
      sediments: a multidisciplinary approach.
AB  - The accumulation rates, the geochronology of metals and PAH contamination, and
      the Microtox toxicity are studied in five sediment cores (50 cm length) covering
      different areas of the Santander Bay, Northern Spain. Chronology given by (210)Pb
      and (137)Cs reveals significant differences in accumulation rates between sites
      (0.2-1.1 cm/year), as well as a variable degree of anthropogenic enrichment
      factors for Fe, Mn, Cu, Pb, Zn, Ni (from 1 to 15) and concentrations of summation
      Sigma 16PAHs (from 0.01 to 23.84 mg/kg dw) in sediments over the last 90 years.
      The results indicate the increasing contamination pressure from industrial and
      urban activities along the Bay. No toxic results from the Microtox test are
      obtained either with pore water or with normalised sediment aqueous extracts
      (European Norm EN 12457), suggesting low water solubility and low availability of
      contaminants in the studied sediments. However, the EC50 values from the Microtox
      Basic Solid Phase Test (BSPT) ranged from 0.03% to 2.35%, showing vertical
      toxicity profiles in accordance with metal and PAHs behaviour. The correlation
      degrees of Microtox BSPT toxicity to chemical concentration in sediment profiles
      are widely variable showing a high site-dependent toxicity. The oligochaete
      Limnodrilus hoffmeisteri has been used as a chronic bioassay over surface
      sediments of two of the studied sites, showing results coherent with the Microtox
      BSPT acute test results. Global results of the present work provide regional
      geochemical baselines for metals and PAHs and toxicological data now make it
      possible to obtain a preliminary quality assessment of the Santander Bay sediment
      profiles.

PMID- 17187861
TI  - Three-dimensional imaging of macular holes with high-speed optical coherence
      tomography.
AB  - OBJECTIVE: To demonstrate the advantages of 3-dimensional imaging of macular hole
      pathology using new-generation high-speed optical coherence tomography (OCT).
      DESIGN: Prospective observational case series. PARTICIPANTS: Twenty-one eyes from
      20 consecutive patients diagnosed with a macular hole. METHODS: A prototype high
      speed OCT system was built based on a Fourier-domain OCT (FD OCT) technology for
      patient examination. The system has achieved sensitivity of approximately 98
      decibels, axial resolution of approximately 4.3 mum in tissue, and an acquisition
      rate of approximately 18,700 axial scans per second. Three-dimensional imaging of
      macular hole pathology was performed based on a raster scan protocol consisting
      of 256x256 axial scans. All patients were imaged with 3-dimensional OCT, Stratus
      OCT, and OCT Ophthalmoscope C7. MAIN OUTCOME MEASURES: Images of macular hole
      pathologies obtained by 3-dimensional OCT and standard OCT instruments. RESULTS:
      The 3-dimensional OCT imaging successfully generated realistic 3-dimensional
      images of the vitreofoveal interface and intraretinal microstructures associated
      with a macular hole. The 3-dimensional overview of the vitreofoveal interface was
      helpful in gaining an immediate understanding of the dynamic interactions of the
      vitreous and fovea. Observations of consecutive en face images in combination
      with conventional longitudinal images and of cross-sectional images in
      combination with sectioned volume images enabled identification of intraretinal
      microstructures and their 3-dimensional extension associated with a macular hole,
      such as subfoveal structural changes after vitreous traction, connection of the
      flap to intraretinal structures, the external limiting membrane (ELM) and its
      disruption, and elevated photoreceptor inner and outer segments delineated by the
      ELM. The appearance of inner-wall images of a macular hole produced by
      photoreceptor inner and outer segment backreflection varied throughout macular
      hole stages. CONCLUSIONS: Three-dimensional imaging of macular holes with high
      speed OCT based on FD OCT technology offers 3-dimensional overviews that
      facilitate understanding of the abnormalities in the vitreofoveal interface. It
      also provides consecutive orthogonal images that allow much more precise and
      minute observation of 3-dimensionally extending intraretinal structural changes
      associated with a macular hole than conventional OCT imaging, especially in the
      photoreceptor inner and outer segments.

PMID- 17187862
TI  - Perceptions of recent ophthalmology residency graduates regarding preparation for
      practice.
AB  - OBJECTIVE: To evaluate young ophthalmologists' perceptions of how well residency
      training prepared them for various aspects of their clinical practice. DESIGN:
      Self-administered survey. PARTICIPANTS: Two hundred sixty-nine United States
      ophthalmologists who have been in practice for < or =5 years. METHODS: A 4-page
      questionnaire was mailed to a randomly selected sample of 900 U.S. members and
      fellows of the American Academy of Ophthalmology who had been in practice for <
      or =5 years. MAIN OUTCOME MEASURES: Comparison of perceived preparedness in
      clinical and nonclinical areas of ophthalmology practice. RESULTS: Two hundred
      sixty-nine surveys were completed and returned (margin of error, +/-5%). Analysis
      of tabulated results indicated that 86% said they were extremely or very well
      prepared to practice comprehensive ophthalmology after residency training. Even
      so, about half of those respondents also desired some additional clinical
      training, and two thirds felt the need for some additional training in surgical
      areas (refractive, oculoplastics/orbital, glaucoma, retina, and pediatric
      ophthalmic surgery). At least 60% reported being not very or not at all well
      prepared in 6 of the nonclinical areas explored (business operations and finance,
      personal financial management, practice management skills, coding and
      reimbursement, political advocacy, and exposure to practice setting models). With
      the exception of personal financial management, most ophthalmologists thought
      training in all of these nonclinical areas was the responsibility of the
      residency training program. CONCLUSION: The transition from residency training to
      successful, efficient, ethical, high-quality ophthalmic practice demands a number
      of skills in addition to diagnostic acumen and surgical ability. In general, the
      U.S. residency program graduates surveyed are comfortable with their clinical
      training, but less so with their training in nonclinical areas. Opportunities to
      help ophthalmologists prepare better for the transition to clinical practice
      after training appear to exist and might be addressed by training programs,
      professional organizations, informal physician networks, and other stakeholders.

PMID- 17187863
TI  - Age-related macular degeneration is associated with incident myocardial
      infarction among elderly Americans.
AB  - OBJECTIVE: To investigate whether age-related macular degeneration (AMD) is
      associated with the development of myocardial infarction (MI) among elderly
      Americans. DESIGN: Population-based cross-sectional and cohort study.
      PARTICIPANTS: Five percent random sample of 2000 to 2003 Medicare enrollees.
      METHODS: The cross-sectional study included the first 2-year (2000 and 2001)
      enrollees who were aged > or =65 years (n = 1,519,086). The cohort study included
      only baseline MI-free enrollees (n = 1445677). MAIN OUTCOME MEASURES: Chronic
      conditions (AMD and type, history of MI, hypertension, and diabetes) were defined
      based on any occurrence of relevant International Classification of Diseases 9
      codes in relevant diagnosis fields of the baseline Medicare claim files. A total
      of 56611 incident MI cases were identified from the follow-up data (2002 and
      2003). RESULTS: Baseline mean age was 76 years, with 60% women and 88% whites.
      The prevalence of neovascular AMD was 2.2% (2.3% in women vs. 1.7% in men and
      2.3% in whites vs. 1.2% in blacks; P<0.01 for both gender and race differences).
      The prevalence of nonneovascular AMD was 8.8% (9.9% in women vs. 7.3% in men and
      9.5% in whites vs. 4.3% in blacks; P<0.01 for both gender and race differences).
      Baseline age-, gender-, and race-adjusted prevalences of hypertension, diabetes,
      and history of MI were 75%, 33%, and 5.00%, respectively, in the neovascular AMD
      group. In contrast, they were 73%, 27%, and 4.68% in the nonneovascular AMD
      group, and 65%, 25%, and 4.54% in the non-AMD group (P<0.01 for comparing the
      prevalence in neovascular and nonneovascular AMD vs. non-AMD groups).
      Prospectively, baseline age-, gender-, race-, hypertension-, and diabetes
      adjusted 2-year incident odds ratios and 95% confidence intervals of MI
      associated with AMD are 1.19 (1.16-1.22) for all persons with AMD, 1.26 (1.20
      1.33) for neovascular AMD, and 1.18 (1.14-1.21) for nonneovascular AMD.
      CONCLUSIONS: AMD is associated with older age, female gender, being white, and
      having a history of MI, hypertension, and diabetes. Furthermore, presence of AMD,
      especially neovascular AMD, is prospectively associated with a higher risk of
      incident MI. These findings, if confirmed by other studies that control for
      smoking and other lifestyle covariables, suggest the possibility of shared common
      antecedents between MI and AMD.

PMID- 17187864
TI  - Anterior uveitis: a manifestation of graft-versus-host disease.
AB  - PURPOSE: To describe the occurrence of anterior uveitis along with systemic
      manifestations of chronic graft-versus-host disease (GVHD) after nonmyeloablative
      allogeneic hematopoietic stem cell transplantation (HSCT) in 3 patients with
      hematologic malignancies. DESIGN: Retrospective small case series. PARTICIPANTS:
      Three patients who underwent HSCT and 4 age- and gender-matched controls for
      cytokine analysis in ocular fluid. METHODS: Interventional study of patients who
      underwent HSCT. Screening for evidence of infectious causes and immunological
      analysis of ocular fluid samples. MAIN OUTCOME MEASURES: Clinical features of
      uveitis and results of aqueous analysis. RESULTS: Anterior uveitis developed
      during an exacerbation of chronic GVHD in 3 patients after allogeneic HSCT for
      hematologic malignancies. Patients exhibited no abnormalities on extensive
      uveitis screening, and in addition, serologic and wide-ranging aqueous analysis
      showed no evidence of recent infections. We observed signs of inflammation in the
      ocular fluid in 2 of 3 patients by the determination of different cytokines. No
      other explanation for uveitis was found except the exacerbation of GVHD.
      Treatment, both systemic and topical, directed to chronic GVHD induced remission
      of uveitis in all patients along with amelioration of other signs of GVHD.
      CONCLUSIONS: Anterior uveitis occurred in the wake of the acute exacerbation of
      chronic GVHD after HSCT and may represent an ocular manifestation of chronic
      GVHD.

PMID- 17187865
TI  - Inter-individual variability in the torque-related patterns of responses for
      mechanomyographic amplitude and mean power frequency.
AB  - The purpose of this study was to examine the inter-individual variability for the
      patterns of responses for mechanomyographic (MMG) amplitude and mean power
      frequency (MPF) versus isometric torque in lower-strength (LS) and higher
      strength (HS) individuals. Twelve participants (mean +/- S.D. age = 25 + 4 years)
      performed two isometric maximal voluntary contractions (MVCs) before and after
      completing nine submaximal step muscle actions (15%, 25%, 35%, 45%, 55%, 65%,
      75%, 85%, and 95% MVC) of the right leg extensors. MMG signals were recorded from
      the vastus lateralis muscle, and MMG amplitude and MPF values were computed for
      each corresponding percentage of the MVC. Polynomial regression analyses
      indicated that the composite MMG amplitude versus isometric torque relationship
      was best fit with a linear model (r(2) = 0.980) for the LS group and a cubic
      model (r(2) = 0.994) for the HS group. The composite MMG MPF versus isometric
      torque relationships were best fit with linear models for both the LS (r(2) =
      0.529) and HS (r(2)=0.591) groups. However, only 66% of the individuals exhibited
      the same linear MMG amplitude patterns as the composite relationship for the LS
      group, whereas only 33% of the individual relationships were cubic for the HS
      group. Only one subject exhibited a positive linear (r(2) = 0.681) relationship
      for the MMG(MPF) versus isometric torque relationship for either the LS or HS
      groups. These findings suggested that strength differences do not affect the
      patterns of responses for MMG amplitude or MPF. The lack of consistency between
      the individual and composite patterns of responses suggested some degree of inter
      individual variability. Therefore, future studies should examine the individual
      patterns of response to draw conclusions about motor control strategies.

PMID- 17187866
TI  - The interplay between inflammation and neurodegeneration in CNS disease.
AB  - This review considers the manner in which inflammation in the CNS contributes to,
      and protects against, neurodegeneration. A series of questions are posed, first
      about primarily inflammatory diseases and the causes of neurodegeneration that
      occurs in them, and then about neurodegenerative diseases and stroke and the role
      that inflammation plays there. Common themes as well as disease-specific
      differences are highlighted in this survey of the recent human disease and animal
      model literature.

PMID- 17187868
TI  - Development of degenerate and species-specific primers for the differential and
      simultaneous RT-PCR detection of grapevine-infecting nepoviruses of subgroups A,
      B and C.
AB  - Based on the nucleotide sequence homology of RNA-1 and RNA-2 of nepoviruses
      isolated from grapevines, three sets of degenerate primers, one for each of the
      three subgroups of the genus (A, B and C), were designed and proved effective for
      RT-PCR detection of subgroups in infected grapevines and herbaceous hosts.
      Primers designed specifically for detecting subgroup A species amplified a
      fragment of 255 bp from samples infected by Grapevine fanleaf virus (GFLV),
      Arabis mosaic virus (ArMV), Tobacco ringspot virus (TRSV) and Grapevine
      deformation virus (GDefV), but not from samples infected by other nepovirus
      species. Similarly, primers for detection of subgroup B nepoviruses amplified a
      390 bp product from samples infected by Grapevine chrome mosaic virus (GCMV),
      Tomato black ring virus (TBRV), Grapevine Anatolian ringspot virus (GARSV) and
      Artichoke Italian latent virus (AILV). The third set of primers amplified a 640
      bp fragment, only from samples infected by subgroup C nepoviruses, i.e Tomato
      ringspot virus (ToRSV) Grapevine Bulgarian latent virus (GBLV), and Grapevine
      Tunisian ringspot virus (GTRSV). These primers were able to detect simultaneously
      all viral species belonging to the same subgroup and to discriminate species of
      different subgroups. Multiplex-PCR detection of subgroup A and B nepoviruses was
      obtained using a specific primer (sense for subgroup A and antisense for subgroup
      B) for each of the species of the same subgroup in combination with the
      degenerate subgroup-specific primers. In this way it was possible to detect four
      different viral species in single samples containing mixtures of viruses of the
      same subgroup. In particular, for viruses of subgroup A (TRSV, GFLV, ArMV and
      GDefV) amplicons of 190, 259, 301 and 371 bp were obtained, whereas amplicons of
      190, 278, 425 and 485 bp, respectively, were obtained from samples infected with
      viruses of subgroup B (GCMV, AILV, GARSV and TBRV).

PMID- 17187869
TI  - A sequence database allowing automated genotyping of Classical swine fever virus
      isolates.
AB  - Classical swine fever (CSF) is a highly contagious viral disease of pigs.
      According to the OIE classification of diseases it is classified as a notifiable
      (previously List A) disease, thus having the potential for causing severe socio
      economic problems and affecting severely the international trade of pigs and pig
      products. Effective control measures are compulsory, and to expose weaknesses a
      reliable tracing of the spread of the virus is necessary. Genetic typing has
      proved to be the method of choice. However, genotyping involves the use of
      multiple software applications, which is laborious and complex. The
      implementation of a sequence database, which is accessible by the World Wide Web
      with the option to type automatically new CSF virus isolates once the sequence is
      available is described. The sequence to be typed is tested for correct
      orientation and, if necessary, adjusted to the right length. The alignment and
      the neighbor-joining phylogenetic analysis with a standard set of sequences can
      then be calculated. The results are displayed as a graph. As an example, the
      determination is shown of the genetic subgroup of the isolate obtained from the
      outbreaks registered in Russia, in 2005. After registration (Irene.greiser
      wilke@tiho-hannover.de) the database including the module for genotyping are
      accessible under http://viro08.tiho-hannover.de/eg/eurl_virus_db.htm.

PMID- 17187871
TI  - An improved, high-throughput method for detection of bluetongue virus RNA in
      Culicoides midges utilizing infrared-dye-labeled primers for reverse
      transcriptase PCR.
AB  - A new rapid (less than 6h from insect-to-results) high-throughput assay that is
      sensitive and specific for detecting BTV RNA in Culicoides biting midges is
      reported. Homogenization and extraction of nucleic acids from individual
      Culicoides specimens were performed in a 96-well plate format using specialized
      beads in a homogenization buffer compatible with cell culture and RNA extraction.
      A portion of homogenate (10%) from each specimen was retained for confirmatory
      infectious virus isolation, while the remaining 90% was used for RNA extraction.
      The RNA was used in a single step reverse transcriptase PCR (RT-PCR) reaction
      with infrared (IR)-dye-labeled primers. The RT-PCR products were visualized in
      agarose gels with an infrared scanner. The adaptation of IR-dye-labeled primers
      in combination with a one step RT-PCR resulted in a detection limit of 0.5 pfu of
      purified BTV RNA. All 24 serotypes of BTV prototype strains and none of the 8
      serotypes of the closely related epizootic hemorrhagic disease virus (EHDV)
      prototype strains were detected.

PMID- 17187870
TI  - Development of a real-time reverse transcription polymerase chain reaction assay
      for detection of marine caliciviruses (genus Vesivirus).
AB  - Marine caliciviruses form a distinct lineage within the genus Vesivirus (family
      Caliciviridae). This group includes vesicular exanthema of swine virus (VESV) and
      San Miguel sea lion virus (SMSV) and other related viruses which have been
      proposed to be marine in origin isolated from a variety of terrestrial and marine
      animals. Rapid and reliable detection of marine caliciviruses is important as
      these viruses appear to be widespread and can cause vesicular disease in a wide
      variety of susceptible hosts including pigs and experimentally infected cattle
      where clinical signs cannot be easily distinguished from foot-and-mouth disease
      (FMD), swine vesicular disease (SVD) and vesicular stomatitis (VS). A real-time
      RT-PCR assay targeting conserved nucleotide sequences in the RNA-dependent RNA
      polymerase (3D) region of the genome successfully detected cell culture-grown
      virus preparations of more than thirty marine calicivirus serotypes. Only the
      atypical SMSV serotypes 8 and 12 failed to be detected, which provided further
      indication of genetic divergence between these and the other calicivirus
      serotypes said to be marine in origin. The real-time RT-PCR assay also
      specifically amplified RNA from samples collected following experimental
      inoculation of pigs with VESV. No cross-reactivity was demonstrated when the
      assay was tested with RNA prepared from representative viruses of FMD, SVD and
      VS. The real-time RT-PCR assay described is a sensitive and specific tool for
      detection and differential diagnosis of these viruses from other vesicular
      disease causing viruses.

PMID- 17187872
TI  - Regulated expression of glycosomal phosphoglycerate kinase in Trypanosoma brucei.
AB  - In Trypanosoma brucei, the PGKB and PGKC genes-encoding phosphoglycerate kinase
      are co-transcribed as part of a polycistronic RNA. PGKB mRNA and the cytosolic
      PGKB protein are much more abundant in the procyclic life-cycle stage than in
      bloodstream forms, whereas PGKC mRNA and glycosomal PGKC protein are specific to
      bloodstream forms. We here show that a sequence between nucleotides 558 and 779
      in the 3'-untranslated region of the PGKC mRNA causes low expression of the
      chloramphenicol acetyltransferase (CAT) reporter gene in procyclic trypanosomes.
      In procyclics, depletion of the RRP45 component of the exosome (3'-->5'
      exonuclease complex) or the 5'-->3' exonuclease XRNA increased the abundance of
      CAT-PGKC mRNA as a consequence of effects on the degradation of precursor and/or
      mature mRNAs. In bloodstream forms, inhibition of both trans splicing and
      transcription resulted in immediate exponential decay of PGKC mRNA with a half
      life of 46 min. Inhibition of transcription alone gave non-exponential kinetics
      and inhibition of splicing alone resulted in a longer apparent half-life. We also
      found that production of mRNAs using T7 polymerase can affect the apparent half
      life, and that large amounts of CAT enzyme may be toxic in trypanosomes.

PMID- 17187873
TI  - Gender differences in the relationship between leptin, insulin resistance and the
      autonomic nervous system.
AB  - OBJECTIVES: Leptin, an important hormonal regulator of body weight, has been
      shown to stimulate the sympathetic nervous system (SNS) in vitro although the
      physiological relevance remains unclear. Increased SNS activity has been
      implicated in the pathogenesis of insulin resistance and an increased
      cardiovascular risk. We have therefore investigated the relationship between
      leptin, insulin resistance and cardiac autonomic activity in healthy young
      adults. 130 healthy men and women age 20.9 years were studied. Insulin
      sensitivity was assessed using the IVGTT and minimal model with simultaneous
      measures of leptin. Cardiac autonomic activity was assessed using spectral
      analysis of heart rate variability. RESULTS: Women showed significantly higher
      fasting leptin, heart rate and cardiac sympathetic activity, and lower insulin
      sensitivity. Men showed inverse correlations between insulin resistance and heart
      rate, and between insulin resistance and cardiac sympatho-vagal ratio. Women, in
      contrast, showed no SNS relationship with insulin resistance, but rather an
      inverse correlation between leptin and the sympatho-vagal ratio, suggesting that
      leptin in women is associated with SNS activity. The correlation remained
      significant after adjustment for BMI and waist-to-hip ratio (beta=-0.33 and
      p=0.008). CONCLUSION: Insulin resistance and SNS activity appear to be linked,
      although the relationship showed marked gender differences, and the direction of
      causality was unclear from this cross-sectional study. Leptin appears to exert a
      greater effect on the SNS in women, possibly because of their greater fat mass.

PMID- 17187874
TI  - A novel approach based on nanotechnology for investigating the chronic actions of
      short-lived peptides in specific sites of the brain.
AB  - This review presents a novel experimental approach for investigating the chronic
      actions of short-lived peptides in specific sites of the brain. This method
      combines the advantages of three different techniques: liposome encapsulation,
      site-specific microinjection and telemetry. First, liposomes can be designed to
      remain located at the injection site for a long period of time, where they
      protect encapsulated peptide from rapid degradation and act as a sustained
      release system. Secondly, microinjection allows the administration of peptides in
      specific sites of the brain with minimal side effects. Finally, using telemetry,
      it is possible to register physiological parameters and their circadian
      variations in undisturbed free-moving animals for several days. Angiotensin-(1-7)
      and angiotensin II were used as peptide models, in order to validate the proposed
      method. Following the unilateral microinjection of the liposome-encapsulated
      peptides into the rostral ventrolateral medulla (RVLM) of Wistar rats, long
      lasting cardiovascular actions were elicited, for several days. Importantly, new
      physiological actions of angiotensin-(1-7) at the RVLM were unmasked: modulation
      of the circadian rhythms of blood pressure and heart rate. It is felt that this
      method can be applied to a wide variety of short-lived bioactive peptides and
      should encounter numerous applications in the field of neurosciences.

PMID- 17187875
TI  - Involvement of stomach ghrelin and hypothalamic neuropeptides in tumor necrosis
      factor-alpha-induced hypophagia in mice.
AB  - This study aimed to clarify the interaction of tumor necrosis factor-alpha (TNF
      alpha), an anorexigenic cytokine, with ghrelin, an orexigenic peptide secreted by
      the stomach lining, and hypothalamic neuropeptides in the regulation of food
      intake in mice. The peripheral administration of TNF-alpha dose-dependently
      decreased the 24-h cumulative food intake compared with the administration of
      saline. Reduced food intake was observed at 6 h and 24 h. The same TNF-alpha
      treatment significantly decreased the plasma level of ghrelin at 6 h and 24 h
      after treatment compared with the control levels. These changes were accompanied
      by a significant reduction in the expression of ghrelin mRNA in the stomach at 24
      h after treatment. TNF-alpha treatment also resulted in a significant increase in
      expression of pro-opiomelanocortin (POMC) mRNA and a significant decrease in
      expression of agouti-related protein (AGRP) mRNA in the hypothalamus at 6 h after
      treatment. Finally, the pre-administration of ghrelin, reversed the TNF-alpha
      induced hypophagia in mice at 6 and 24 h. Taken together, these findings suggest
      that hypothalamic POMC and AGRP and stomach ghrelin may be involved in TNF-alpha
      induced hypophagia in mice.

PMID- 17187876
TI  - Expression and activity of cocaine- and amphetamine-regulated transcript
      peptide(1-39) in the rat.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptide consists of a family
      of peptides. Expression of the peptide fragment CART(1-39) was explored in the
      rat using an antiserum directed against CART(1-39) of the short form of the human
      CART prohormone. CART(1-39)-immunoreactivity, herein referred to as irCART, was
      detected in the rat central and peripheral nervous tissues with a pattern similar
      to that labeled with the antiserum CART(55-102) or CART(79-102). For example,
      irCART cells were detected in the hypothalamus, pons, medulla oblongata, spinal
      cord, and adrenal medulla. In urethane-anesthetized rats, CART(1-39) (0.05 to 2
      nmol) by intrathecal injection did not cause a significant change of blood
      pressure or heart rate, but potentiated the pressor effects of glutamate injected
      intrathecally. Lastly, the effect of CART(1-39) on intracellular calcium
      concentrations [Ca2+]i was assessed and compared to that caused by CART(55-102)
      in cultured rat cortical neurons using the microfluorimetric method. CART(1-39)
      (100 nM) induced two types of responses in a population of cortical neurons: 1) a
      slowly rising increase in [Ca2+]i superimposed with oscillations, and 2) a fast
      increase followed by a sustained increase of [Ca2+]i. CART(55-102) caused only a
      slowly rising increase in [Ca2+]i in cortical neurons. Our result shows that the
      expression pattern of irCART in the rat nervous system and the potentiating
      action of CART(1-39) on glutamate-induced pressor response is similar to that
      reported for CART(55-102); but the calcium mobilizing action of CART(1-39)
      differs from that of CART(55-102), suggesting the possible existence of multiple
      CART receptors coupled to different calcium signaling pathways.

PMID- 17187877
TI  - Total ghrelin plasma level in patients with the restrictive type of anorexia
      nervosa.
AB  - Ghrelin is produced mainly in the stomach and is an essential link of the brain
      gut axis. Ghrelin stimulates hunger centers in hypothalamus controlling food
      intake and body mass gain. The aim of the study is to analyze the total ghrelin
      plasma level in patients suffering from restrictive type of anorexia nervosa (AN
      R). According to DSM-IV classification a group of 30 AN-R patients was
      investigated before and after 3 and 6 months of therapy. Therapy included
      normocaloric diet and cognitive-behavioral psychotherapy (CBT). The control group
      consisted of 20 girls without any eating disorders. Before the therapy the total
      ghrelin plasma level in AN-R patients was significantly higher than in the
      control group. After 3 and 6 months of treatment the total ghrelin plasma level
      in AN-R patients was significantly lower than in the control group. In AN-R
      patients, the total ghrelin plasma level is connected with the pathological
      feeding behavior.

PMID- 17187878
TI  - Detection of MMP activity in living cells by a genetically encoded surface
      displayed FRET sensor.
AB  - Matrix metalloproteinases (MMPs) are secretory endopeptidases. They have been
      associated with invasion by cancer-cell and metastasis. Previous studies have
      demonstrated that proteolytic activity could be detected using fluorescence
      resonance energy transfer (FRET) with mutants of GFP. To monitor MMP activity, we
      constructed vectors that encoded a MMP Substrate Site (MSS) between YFP and CFP.
      In vitro, YFP-MSS-CFP can be used to detect MMP activity and 1,10-phenathroline
      inhibition of MMP activity. In living cells, MMPs are secreted proteins and act
      outside of the cell, and therefore YFP-MSS-CFPdisplay was anchored on the
      cellular surface to detect extracellular MMP. A pDisplay-YC vector expressing the
      YFP-MSS-CFPdisplay on the cellular surface was transfected into MCF-7 cells that
      expressed low levels of MMP. Efficient transfer of energy from excited CFP to YFP
      within the YFP-MSS-CFPdisplay molecule was observed, and real-time FRET was
      declined when MCF-7 was incubated with MMP2. However, no such transfer of energy
      was detected in the YFP-MSS-CFPdisplay expressing MDA-MB 435s cells, in which
      high secretory MMP2 were expressed. The FRET sensor YFP-MSS-CFPdisplay can
      sensitively and reliably monitor MMP activation in living cells and can be used
      for high-throughput screening of MMP inhibitors for anti-cancer treatments.

PMID- 17187879
TI  - Intravenously injected mesenchymal stem cells home to viable myocardium after
      coronary occlusion and preserve systolic function without altering infarct size.
AB  - BACKGROUND: The purpose of this study was to determine whether murine mesenchymal
      stem cells (MSC) are able to home to the viable myocardium when injected
      intravenously and attenuate cardiac dysfunction and ventricular remodeling
      associated with myocardial infarction. METHODS AND RESULTS: Murine bone marrow
      cells were negatively selected for lineage markers and adherent MSC
      differentiated into adipocytes and osteocytes following treatment in culture. Two
      weeks after coronary occlusion that resulted in a permanent transmural infarct we
      observed a significant drop in LV systolic pressure, dP/dt(max), dP/dt(min),
      ESPVR and E(max) and a significant increase in end-diastolic volume in vivo.
      Femoral vein injection of MSC 1 h after occlusion attenuated the cardiac
      dysfunction without altering infarct size, or end-diastolic volume. Injected MSC
      pre-labeled with fluorescent paramagnetic microspheres were observed scattered in
      noninfarcted regions of the myocardium. Flow cytometry of whole heart digests
      after intravenous injection of MSC labeled with either fluorescent microspheres
      or fluorescent PKH26 dye demonstrated that infarcted hearts from mice that
      received MSC injections contained significantly more cells that integrated into
      the heart (20x) than those from uninfarcted controls. CONCLUSION: We conclude
      that intravenously injected MSC were able to home to viable myocardium and
      preserve systolic function by 2 weeks following ligation. The preserved
      contractility is likely an MSC-mediated paracrine response since infarct
      morphology was unchanged and labeled cells observed at two weeks exhibited the
      same characteristics as the injected MSC. These data underscore the importance of
      using MSC as a potential therapeutic intervention in preserving cardiac function
      following infarction.

PMID- 17187880
TI  - Raised leptin concentrations among South Asian patients with chronic heart
      failure.
AB  - BACKGROUND: The disease presentation of chronic heart failure (CHF) is considered
      to progress with metabolic deterioration, underlined by changes in adipose
      associated hormones (adipocytokines). However, little is known about ethnic
      variations of adipocytokines amongst CHF patients, in particular South Asians,
      who are at an increased risk of CHF. METHODS: Using a cross-sectional study,
      South Asians (n=106) and Caucasians (n=105) living in the UK were compared by CHF
      status. We investigated ethnic differences in adipocytokines (leptin,
      adiponectin, tumor necrosis factor (TNF)alpha), and their association with CHF.
      Patients with mild to moderate CHF were recruited from heart failure clinics (47
      Caucasian, 54 South Asian), and compared to healthy controls. Metabolic
      parameters (including insulin resistance using HOMA modelling), echocardiography
      and brain natriuretic peptide (BNP) were measured amongst patients and healthy
      controls, and compared across and within ethnic groups. RESULTS: Mean (log
      transformed) plasma leptin concentrations were highest amongst South Asian
      patients, being 5.25% (95%CI: 1.50-9.02) higher than Caucasian patients
      (P=0.007), and similarly raised with respect to controls (P< or =0.04). Indices
      of insulin resistance were higher amongst CHF patients compared with controls,
      with no ethnic variation. In addition to age, female gender and body-mass index,
      levels of leptin were also associated with South Asian ethnicity (P<0.001),
      insulin resistance (P=0.02), smoking habit (P=0.01) and HDL cholesterol
      (P=0.004). Levels of adiponectin showed no ethnic variation, but were associated
      with CHF and a previous history of myocardial infarction (P<0.001). On
      multivariate regression analysis of patients and healthy controls, CHF was
      independently associated with smoking habit, adiponectin and insulin resistance
      (all P<0.01). CONCLUSION: Metabolic abnormalities are present in CHF, which in
      turn, are influenced by ethnicity. The role of adipocytokines in CHF
      pathophysiology and prognosis merits further study.

PMID- 17187881
TI  - Fish oil does not improve defibrillation efficacy.

PMID- 17187882
TI  - Giant true saphenous vein graft aneurysm causing cardiac compression: a rare
      cause of atrial flutter.
AB  - A 67 year old man presented with new-onset atrial flutter. He had a history of
      coronary artery bypass graft (CABG) surgery on two occasions. Subsequent
      investigation revealed the presence of a large saphenous vein graft (SVG)
      aneurysm compressing the right heart. We postulate that the SVG aneurysm was the
      precipitating cause for the atrial flutter. This case is the first in the
      literature to document an atrial arrhythmia as the presenting feature of a SVG
      aneurysm.

PMID- 17187883
TI  - Removal of contaminating DNA from polymerase chain reaction using ethidium
      monoazide.
AB  - The presence of exogenous DNA in PCR reagents and DNA polymerase is a common
      occurrence. In particular, the amplification of 16S rRNA genes with universal
      primers for non-culture-based study is often hampered by the formation of false
      positives. Here, we describe the use of ethidium monoazide (EMA) to eliminate
      contaminating DNA in a polymerase chain reaction. The advantage of the proposed
      methodology is the retention of the highly sensitive nature of PCR with the
      ability to amplify template DNA at concentrations lower than those of
      contaminating DNA. The treatment of PCR master mix with EMA concentrations that
      exceeded those required to remove contaminating DNA can interfere with the
      amplification of low-template concentrations. The methodology presented is
      straightforward and can be accomplished within 10 min.

PMID- 17187884
TI  - A reappraisal of the role of vesicourethral anastomosis biopsy in patient
      candidates for salvage radiation therapy after radical prostatectomy.
AB  - BACKGROUND AND PURPOSE: To investigate the usefulness of vesicourethral
      anastomotic biopsy (VUBx) in patients who are candidates for salvage radiotherapy
      (SalvRT) after radical prostatectomy (RRP). MATERIAL AND METHODS: From 1992 to
      2001, 98 patients with a PSA failure (PSAf) after RRP underwent SalvRT to the
      prostatic bed (median dose 70 Gy). In 50/98 patients the VUBx was positive, in 26
      negative; 22 patients underwent SalvRT without a prior VUBx. The prognostic
      impact on biochemical disease-free survival (bNEDs) of histologic confirmation of
      the local failure was evaluated retrospectively. RESULTS: In the 40 patients with
      pre-RT PSA < or = 0.9 ng/mL, no additional prognostic information derived from
      the VUBx, while, for higher PSA values, a positive histology resulted as a
      covariate independently predictive of post-RT outcome (5-year bNEDs: 74% vs 42%
      in the 35 and 23 patients with a positive or negative/not performed VUBx,
      respectively, P=.03), together with pT, pre-RT PSA < or = 1.5 ng/mL, and PSA
      doubling time. CONCLUSIONS: In case of PSAf after RRP, VUBx before SalvRT seems
      unnecessary for PSA < or = 0.9 ng/mL. For higher values, a positive VUBx seems to
      always justify a SalvRT, which may not be recommendable, given the nonnegligible
      risk of an already micrometastatic disease, if the biopsy results are negative.

PMID- 17187885
TI  - A novel approach for the improvement of stress resistance in wine yeasts.
AB  - During wine production yeast cells are affected by several stress conditions that
      could affect their viability and fermentation efficiency. In this work we
      describe a novel genetic manipulation strategy designed to improve stress
      resistance in wine yeasts. This strategy involves modifying the expression of the
      transcription factor MSN2, which plays an important role in yeast stress
      responses. The promoter in one of the genomic copies of this gene has been
      replaced by the promoter of the SPI1 gene, encoding for a cell wall protein of
      unknown function. SPI1 is expressed at late phases of growth and is regulated by
      Msn2p. This modification allows self-induction of MSN2 expression. MSN2 gene
      transcription, Msn2p protein levels and cell viability increase under several
      stress conditions in the genetically modified strain. The expression of stress
      response genes regulated by Msn2p also increases under these situations. Cells
      containing this promoter change are able to carry out vinifications at 15 and 30
      degrees C with higher fermentation rates during the first days of the process
      compared to the control strain.

PMID- 17187886
TI  - Phage types, virulence genes and PFGE profiles of Shiga toxin-producing
      Escherichia coli O157:H7 isolated from raw beef, soft cheese and vegetables in
      Lima (Peru).
AB  - The present study was conducted in Lima Metropolitana to evaluate the prevalence
      of Shiga toxin-producing Escherichia coli (STEC) O157:H7 in raw beef, raw ground
      beef, soft cheese and fresh vegetables, sampled at different markets in the city.
      Between October 2000 and February 2001, 407 food samples were collected from
      different markets in the 42 districts of Lima Metropolitana. Samples were assayed
      for E. coli O157 by selective enrichment in modified Tryptic Soy Broth containing
      novobiocin, followed by immunomagnetic separation (IMS) and plating onto sorbitol
      MacConkey agar supplemented with cefixime and potassium tellurite. Fifty (12.3%)
      of 407 food samples resulted positive for E. coli O157 isolation (23 of 102
      ground beef; 15 of 102 beef meat; eight of 102 soft cheese and four of 101 fresh
      vegetables). Thirty-five E. coli O157 isolates were further analysed for the
      presence of virulence genes. All 35 were positive by PCR for O157 rfbE, fliCh7,
      eae-gamma1 and ehxA genes. In addition, genes encoding Shiga toxins were detected
      in 33 of 35 isolates, five isolates (14%) encoded stx(1), stx(2), and 28 (80%)
      stx2 only. The isolates were of seven different phage types (PT4, PT8, PT14,
      PT21, PT34, PT54, and PT87) with three phage types accounting for 80% of
      isolates: PT4 (15 isolates), PT14 (8 isolates), and PT21 (5 isolates).
      Interestingly, the majority (31 of 35; 89%) of E. coli O157:H7 isolates
      characterized in this study belonged mainly to the phage types previously found
      in STEC O157:H7 strains associated with severe human disease in Europe and
      Canada. Pulsed-field gel electrophoresis (PFGE) of 32 isolates revealed 14 XbaI
      PFGE groups (I to XIV) of similarity >85%, with 23 (72%) isolates grouped in five
      clusters. Some isolates from different districts presented a high clonal
      relatedness. Thus, PFGE group VIII clustered eleven strains from nine different
      districts. The broad range of PFGE subtypes found in this study demonstrates the
      natural occurrence of many genetic variants among STEC O157:H7 spread in Lima.

PMID- 17187888
TI  - Construction of equalized short hairpin RNA library from human brain cDNA.
AB  - Short hairpin RNA (shRNA) library is a powerful new tool for high-throughput loss
      of-function genetic screens in mammalian cells. An shRNA library can be
      constructed from synthetic oligonucleotides or enzymatically cleaved natural
      cDNA. Here, we describe a new method for constructing equalized shRNA libraries
      from cDNA. First, enzymatically digested cDNA fragments are equalized by a
      suppression PCR-based method modified from suppression subtractive hybridization.
      The efficiency of equalization was confirmed by quantitative real-time PCR. The
      fragments are then converted into an shRNA library by a series of enzymatic
      treatments. With this new technology, we constructed a library from human brain
      cDNA. Sequence analysis showed that most of the randomly selected clones had
      inverted repeat sequences converted from different cDNA. After transfecting HEK
      293T cells and detecting gene expression, three out of eight clones were
      demonstrated to significantly inhibit their target genes.

PMID- 17187887
TI  - Study on the microflora and biochemistry of cocoa fermentation in the Dominican
      Republic.
AB  - Cocoa fermentation was monitored at the IDIAF (Instituto Dominicano de
      Investigaciones Agropecuarias y Forestales) "Mata Larga" experimental station, in
      San Francisco de Macoris, Dominican Republic. The maximum average fermentation
      temperature reached 51 degrees C after 48 h and the pH reached 4.5 after 144 h of
      fermentation. A significant decrease in glucose, fructose and citric acid was
      seen in the pulp over the first 48 h. There was a delay of 24 h between maximum
      microbial growth and maximum concentrations of the respective metabolites, which
      occurred after 48 h for ethanol and after 72 h for acetic acid. A maximum
      concentration in lactic acid was found after around 120 h of fermentation. The
      aerobic mesophilic flora increased from 6.1x10(6) to a maximum of 4.2x10(7) CFU
      g(-1) of dry matter after 48 h of fermentation. Yeasts displayed maximum
      development after 24 h (6.1x10(7) CFU g(-1) of dry matter), whilst for lactic and
      acetic acid bacteria it occurred after 48 h (7.3x10(7) and 1.5x10(8) CFU g(-1) of
      dry matter respectively). The yeasts isolated belonged to the genera
      Hanseniaspora and Candida, the lactic acid bacteria to the genus Lactobacillus,
      and the acetic acid bacteria to the genus Acetobacter. The differences compared
      to other fermentation trials concerned the micropopulation from a qualitative
      point of view.

PMID- 17187890
TI  - Rising prevalence of type 2 diabetes in rural Bangladesh: a population based
      study.
AB  - The aim of the study was to determine the temporal changes in the prevalence of
      type 2 diabetes mellitus and its associated risk factors in a rural population of
      Bangladesh. A total of 4757 subjects age >/=20 years both male and female were
      enrolled randomly in a cross-sectional study in 1999. The same area and
      population was reinvestigated in 2004 following the same selection procedure, on
      a sample of 3981 individuals. Structural and economical changes were noted for
      the last 5 years in the locality. An increased prevalence of diabetes was found
      with 6.8% in the present survey compared with 2.3% in the earlier survey
      (p<0.05). Age, BMI and systolic blood pressure were found to be significant risk
      factors following both for FBG and for OGTT. WHR was found to be a significant
      risk factor for men only. A substantial agreement was observed between FBG and
      OGTT (kappa 0.63) compared to the previous investigation in 1999 (kappa 0.40).
      Differences in the indices of obesity, that is BMI, WHR and waist girth, may in
      part explain the increased prevalence, which in turn may explain due to fast
      expanded urbanization. The state of affairs warrants immediate measures necessary
      to prevent the epidemic particularly in the localities that are in the transition
      phase from rural to semi-urban facilities.

PMID- 17187891
TI  - Daily-life activities and in-shoe forefoot plantar pressure in patients with
      diabetes.
AB  - OBJECTIVE: To assess differences regarding in-shoe forefoot plantar pressure (PP)
      in patients with diabetes during various daily-life activities. RESEARCH DESIGN
      AND METHODS: In-shoe PP was measured in 93 patients during: level walking, ramp
      and stair walking, turning in different settings and while performing the Up & Go
      test. Separate PPs were determined for the big toe and metatarsal (mt) regions
      one to five. RESULTS: Across all activities, similar PPs were measured in the big
      toe and mt-1 to mt-3 region. Lower PPs were measured in mt-4 and mt-5 region. PPs
      during level walking were mostly higher when compared to the other activities
      (p</=.030). Turning while level walking resulted in higher PPs than turning while
      performing the other activities (p</=.033). Higher PPs were measured for both
      ramp and stair ascending when compared to descending (p</=.001). In the big toe
      region, stair descending resulted in higher PPs than ascending (p</=.001). Across
      all activities, patients with neuropathy had lower PPs (overall mean 28kPa) than
      patients without neuropathy. CONCLUSIONS: Level walking resulted in the highest
      forefoot PPs during daily-life activities. Patients with neuropathy had lower PPs
      than patients without neuropathy.

PMID- 17187889
TI  - Purification and characterization of a keratinolytic metalloprotease from
      Chryseobacterium sp. kr6.
AB  - The Chryseobacterium sp. kr6 strain has been described as a highly keratinolytic
      bacterium showing effective feather-degrading and de-hairing activities. A
      keratinase Q1 enzyme was purified from Chryseobacterium sp. kr6 culture by Phenyl
      Sepharose and Superose 12HR chromatography. This enzyme showed a specific
      activity of 967U/mg for keratin azure. Electrophoresis under denaturing
      conditions showed a monomeric protein with approximately 64kDa. The enzyme showed
      pH and temperature optima of 8.5 and 50 degrees C, respectively. The inhibitory
      effect of EDTA, EGTA and 1,10-phenanthroline characterized Q1 enzyme as a Zn
      metalloprotease. Its activity was increased by three-fold in the presence of
      Ca(2+). ESI-MS/MS analysis of peptides generated from a tryptic digestion
      revealed sequence homology which may characterize the Q1 keratinase as a member
      of the M14 metalloprotease family, with a consensus glycosylation region similar
      to proteins from Chryseobacerium meningosepticum.

PMID- 17187892
TI  - The role of degradant profiling in active pharmaceutical ingredients and drug
      products.
AB  - Forced degradation studies are used to facilitate the development of analytical
      methodology, to gain a better understanding of active pharmaceutical ingredient
      (API) and drug product (DP) stability, and to provide information about
      degradation pathways and degradation products. In order to fulfill development
      and regulatory needs, this publication provides a roadmap for when and how to
      perform studies, helpful tools in designing rugged scientific studies, and
      guidance on how to record and communicate results.

PMID- 17187893
TI  - Modeling potential vadose-zone transport of nitrogen from onsite wastewater
      systems at the development scale.
AB  - Water in the urban front-range corridor of Colorado has become an increasingly
      critical resource as the state faces both supply issues as well as anthropogenic
      degradation of water quality in several aquifers used for drinking water. A
      proposed development (up to 1100 homes over two quarter-quarter sections) at Todd
      Creek, Colorado, a suburb of Westminster located about 20 miles northeast of
      Denver, is considering use of onsite wastewater systems (OWS) to treat and remove
      domestic wastewater. Local health and environmental agencies have concerns for
      potential impacts to local water quality. Nitrogen treatment in the vadose zone
      and subsequent transport to ground water at a development scale is the focus of
      this investigation. The numerical model HYDRUS 1D was used, with input based on
      site-specific data and several transport parameters estimated from statistical
      distribution, to simulate nitrate concentrations reaching ground water. The model
      predictions were highly sensitive to mass-loading of nitrogen from OWS and the
      denitrification rate coefficient. The mass loading is relatively certain for the
      large number of proposed OWS. However, reasonable values for the denitrification
      rate coefficients vary over three orders of magnitude. Using the median value
      from a cumulative frequency distribution function, based on rates obtained from
      the literature, resulted in simulated output nitrate concentrations that were
      less than 1% of regulatory maximum concentrations. Reasonable rates at the lower
      end of the reported range, corresponding to lower 95% confidence interval
      estimates, result in simulated nitrate concentrations reaching groundwater above
      regulatory limits.

PMID- 17187895
TI  - Fomite transmission in head lice.
AB  - Control of various infestations requires an accurate understanding of
      transmission. After thousands of years of lice infestation, scientific
      documentation of indirect contact transmission has been substantiated. Lice can
      be transferred in the egg, instar, and adult stages. Lice have now been shown in
      the laboratory to be readily dislodged by air movements such as blow-drying one's
      hair, combing, and toweling. Moreover, passive transfer to adjoining fabric is
      also frequently observed. Louse transmission by fomites occurs more frequently
      than has been commonly believed. Close proximity suffices to increase the
      likeliness of a new infestation. Thus louse control measures should take account
      of fomite transmission and include screening of all individuals within an
      infested person's immediate circle of contact, laundering of everything within
      the infested individuals' bed or quarantining of such material for 10 days,
      thorough vacuuming of floors, carpets, upholstery, with a standard vacuum
      cleaner.

PMID- 17187897
TI  - The modified Trait and State Food-Cravings Questionnaires: development and
      validation of a general index of food craving.
AB  - In the present study, the multidimensional Trait and State Food Cravings
      Questionnaires (FCQ-T and FCQ-S), as developed by Cepeda-Benito, Gleaves,
      Williams, and Erath, [2000. The development and validation of the State and Trait
      Food Cravings Questionnaires. Behavior Therapy, 31, 151-173], were modified in
      order to construct an index of general food craving instead of specific food
      craving. The factor structure, validity and reliability of the modified
      questionnaires, renamed as the Trait and State General Food Cravings
      Questionnaires (G-FCQ-T and G-FCQ-S), were investigated in three separate
      studies. Firstly, exploratory factor analyses were conducted, which yielded a G
      FCQ-T with a four-factor structure, that was considerably shorter as compared to
      the original (nine-factor) FCQ-T, and a G-FCQ-S of which the factor structure was
      highly comparable to the original FCQ-S. Secondly, in an attempt to replicate the
      factor structures of the G-FCQ-T and the G-FCQ-S as found in Study 1,
      confirmative factor analyses were performed. Results indicated adequate fits for
      both questionnaires. In addition, the test-retest reliability of both versions
      was satisfactory and an analysis of the construct validity generally revealed the
      expected results. In Study 3, the validity of the state version of the G-FCQ was
      further investigated by relating scores on this questionnaire to indices of food
      deprivation and satiation. Results indicated that the G-FCQ-S indeed measures
      food craving as a variable state, which is influenced by situational and temporal
      variables. Altogether, it can be concluded that the G-FCQ-T and G-FCQ-S are both
      reliable and valid measures of general trait-like and state-dependent food
      craving.

PMID- 17187896
TI  - Ultraviolet recall reaction after total body irradiation, etoposide, and
      methotrexate therapy.
AB  - Ultraviolet (UV) reactivation reactions are rare and can occur in areas of prior
      sunburn or UV light therapy after the administration of chemotherapy,
      antibiotics, and other medications. Reactions may occur within days, as described
      after methotrexate therapy, or may appear months later, as described with
      ampicillin. Such reactions have been variably termed "UV recall," "sunburn
      recall," "photo recall," and "photodermatitis reactivation," making
      classification difficult. We report a UV reactivation reaction in a patient with
      acute lymphocytic leukemia treated with total body irradiation, etoposide, and
      methotrexate. We propose the terms "UV recall" and "UV enhancement" be used in
      future reports to classify UV reactivation reactions in a scheme analogous to the
      terminology for cutaneous reactions after radiotherapy.

PMID- 17187898
TI  - Hand hygiene compliance.

PMID- 17187899
TI  - Angiogenesis induced by novel peptides selected from a phage display library by
      screening human vascular endothelial cells under different physiological
      conditions.
AB  - Angiogenesis is a process modulated by several endogenous vascular growth factors
      as well as by oxygen conditions. For example VEGF failed to induce useful
      therapeutic angiogenesis in clinical trials. We used a combinatory phage display
      peptide library screening on human umbilical endothelial cells under normoxia and
      hypoxia conditions in order to identify novel peptides that bind endothelial
      cells. The identified peptides induced angiogenesis as demonstrated by
      endothelial cell proliferation, migration and tube formation. Injection of
      peptides into the ears of mice resulted in increased numbers of blood vessels.
      Peptides did not induce VEGF receptor gene expression indicating a possible VEGF
      unrelated mechanism.

PMID- 17187900
TI  - Neuropeptide Y modulation of ethanol intake: effects of ethanol drinking history
      and genetic background.
AB  - Intracerebroventricular administration of NPY suppresses ethanol intake in
      selectively bred alcohol-preferring rat lines, but not in rats selectively bred
      for low ethanol drinking or in unselected Wistar rats, when access to ethanol is
      limited to 2h/day. However, when rats undergo chronic (24h/day) ethanol drinking
      (or exposure to ethanol by vapor inhalation) and have periods of imposed ethanol
      abstinence, the reductions in ethanol drinking following NPY administration are
      enhanced in alcohol-preferring rats and are also observed in unselected Wistar
      rats. Thus, sensitivity to the effects of NPY on ethanol drinking appears to be
      altered by selective breeding for ethanol preference and by a prior history of
      chronic but intermittent exposure to ethanol.

PMID- 17187901
TI  - The protective effect of fish n-3 fatty acids on cerebral ischemia in rat
      hippocampus.
AB  - Reactive oxygen species (ROS) have been implicated in the pathogenesis of
      cerebral injury after ischemia-reperfusion (I/R). Fish n-3 essential fatty acids
      (EFA), contain eicosapentaenoic acids (EPA) and docosahexoenoic acids (DHA),
      exhibit antioxidant properties. DHA is an important component of brain membrane
      phospholipids and is necessary for the continuity of neuronal functions. EPA
      prevents platelet aggregation and inhibits the conversion of arachidonic acid
      into thromboxane A(2) and prostaglandins. They have been suggested to be
      protective agents against neurological and neuropsychiatric disorders. In this
      study, the neuroprotective effects of fish n-3 EFA on oxidant-antioxidant systems
      and number of apoptotic neurons of the hippocampal formation (HF) subjected to
      cerebral I/R injury was investigated in Sprague-Dawley rats. Six rats were used
      as control (Group I). Cerebral ischemia was produced by occlusion of both the
      common carotid arteries combined with hypotension for 45 min, followed by
      reperfusion for 30 min, in rats either on a standard diet (Group II) or a
      standard diet plus fish n-3 EFA (Marincap((R)), 0.4 g/kg/day, by gavage) for 14
      days (Group III). At the end of procedures, the rats were sacrificed and their
      brains were removed immediately. The levels of malonedialdehyde (MDA) and nitric
      oxide (NO) and activities of superoxide dismutase (SOD) and catalase (CAT) were
      measured in left HF. In addition, the number of apoptotic neurons was counted by
      terminal transferase dUTP nick end labelling (TUNEL) assay in histological
      samples of the right HF. We found that SOD activities and MDA levels increased in
      Group III rats compared with Group II rats. On the other hand, CAT activities and
      NO levels were found to be decreased in Group III rats compared with Group II
      rats. Additionally, the number of apoptotic neurons was lower in Group III in
      comparison with Group II rats. The present findings suggest that fish n-3 EFA
      could decrease the oxidative status and apoptotic changes in ischemic rat
      hippocampal formation. Dietary supplementation of n-3 EFA may be beneficial to
      preserve or ameliorate ischemic cerebral vascular disease.

PMID- 17187902
TI  - Biochemical analysis of ecto-nucleotide pyrophosphatase phosphodiesterase
      activity in brain membranes indicates involvement of NPP1 isoenzyme in
      extracellular hydrolysis of diadenosine polyphosphates in central nervous system.
AB  - Synaptosomes and plasma membranes obtained from rat brain display ectoenzymatic
      hydrolytic activity responsible for hydrolysis of the
      neurotransmitter/neuroregulatory nucleotides diadenosine polyphosphates. Intact
      synaptosomes and plasma and synaptic membranes isolated by sucrose-gradient
      ultracentrifugation from several brain regions (hypothalamus, hippocampus,
      temporal cortex, frontal cortex striatum and cerebellum) degraded the fluorogenic
      substrates diethenoadenosine polyphosphates up to ethenoadenosine as by-product.
      Purified ectoenzyme cleaved substrates always releasing the mononucleotide
      moieties ethenoadenosine 5'-monophosphate and the corresponding ethenoadenosine
      (n-1) 5'-phosphate. Ectoenzymatic hydrolysis reached maximal activity at pH 9.0
      (pH range 6.5-9.0) and was activated by Ca(2+) and Mg(2+) ions, with maximal
      effects around 2.0 mM cation. EDTA drastically reduced activity and Zn(2+) was
      required for enzyme reactivation. Hydrolysis of substrates followed hyperbolic
      kinetics with K(m) values in the 3-10 microM range. Diadenosine polyphosphates
      and heparin behaved as competitive inhibitors in the enzymatic hydrolysis of
      diethenoadenosine polyphosphates and AMP, ATP, alpha,beta-methyleneADP, ADPbetaS
      ATPgammaS, beta,gamma-methyleneATP, suramin and diethyl pyrocarbonate were also
      inhibitors. Ectoenzymatic activity shared the typical characteristics of members
      of the ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP) family and
      inhibition data suggest that NPP1 ectoenzyme is involved in the cleavage of
      extracellular diadenosine polyphosphates in brain. Synaptic membranes from
      cerebellum, hypothalamus and hippocampus presented the highest activities and no
      activity differences were observed between young and aged animals. However,
      plasma membranes showed a more homogeneous distribution of ectoenzymatic activity
      but a general increase was detected in aged animals. Enhancement of ectoenzymatic
      diadenosine polyphosphate cleaving activity found in plasma membranes from old
      animals could play a deleterious role in aged brain by limiting neuroprotective
      effects reported for extracellular diadenosine tetraphosphate.

PMID- 17187904
TI  - Synthesis and evaluation of N-acetyl-L-tyrosine based compounds as PPARalpha
      selective activators.
AB  - The development of type 2 diabetes in obese individuals is linked to lipid
      accumulation in non-adipose tissues. A series of N-acetyl-L-tyrosine derivatives
      were synthesized and evaluated for PPAR transactivation. Compounds 4d and 4f were
      found to show better PPARalpha transactivation as compared to PPARgamma.
      Molecular docking analysis was carried out to study their important interactions
      with the active site of PPARalpha.

PMID- 17187903
TI  - ADAM-10 over-expression increases cortical synaptogenesis.
AB  - Cortical cholinergic, glutamatergic and GABAergic terminals become upregulated
      during early stages of the transgenic amyloid pathology. Abundant evidence
      suggests that sAPP alpha, the product of the non-amyloidogenic alpha-secretase
      pathway, is neurotrophic both in vitro and when exogenously applied in vivo. The
      disintegrin metalloprotease ADAM-10 has been shown to have alpha-secretase
      activity in vivo. To determine whether sAPP alpha has an endogenous biological
      influence on cortical presynaptic boutons in vivo, we quantified cortical
      cholinergic, glutamatergic and GABAergic presynaptic bouton densities in either
      ADAM-10 moderate expressing (ADAM-10 mo) transgenic mice, which moderately
      overexpress ADAM-10, or age-matched non-transgenic controls. Both early and late
      ontogenic time points were investigated. ADAM-10 mo transgenic mice display
      significantly elevated cortical cholinergic, glutamatergic and GABAergic
      presynaptic bouton densities at the early time point (8 months). Only the
      cholinergic presynaptic bouton density remains significantly elevated in late
      staged ADAM-10 mo transgenic animals (18 months). To confirm that the observed
      elevations were due to increased levels of endogenous murine sAPP alpha,
      exogenous human sAPP alpha was infused into the cortex of non-transgenic control
      animals for 1 week. Exogenous infusion of sAPP alpha led to significant
      elevations in the cholinergic, glutamatergic and GABAergic cortical presynaptic
      bouton populations. These results are the first to demonstrate an in vivo
      influence of ADAM-10 on neurotransmitter-specific cortical synaptic plasticity
      and further confirm the neurotrophic influence of sAPP alpha on cortical
      synaptogenesis.

PMID- 17187906
TI  - The bacterial second messenger cyclic diGMP exhibits potent adjuvant properties.
AB  - The identification of new adjuvants is a critical need in vaccinology. In this
      work, it is demonstrated that bis-(3',5')-cyclic dimeric guanosine monophosphate
      (cdiGMP) exhibits potent adjuvant properties. Subcutaneous co-administration of
      cdiGMP with beta-galactosidase (beta-Gal) to mice resulted in the elicitation of
      significantly higher antigen-specific serum IgG titres than in animals receiving
      beta-Gal alone. Strong cellular immune responses, which were characterized by a
      balanced Th1/Th2 pattern, were also observed in response to the beta-Gal protein
      and a peptide encompassing its MHC class I-restricted epitope in immunized
      animals. These results suggest that cdiGMP represents a promising adjuvant for
      vaccine development.

PMID- 17187905
TI  - Stress sources in nursing practice. Evolution during nursing training.
AB  - A cohort study was carried out in order to evaluate the evolution of nursing
      students' perception of stressors associated with clinical practice. Sixty-nine
      students answered the KEZKAK questionnaire about nursing stressors [Zupiria X.,
      Uranga M.J., Alberdi, M.J., Barandiaran, M., 2003b. Kezkak: cuestionario bilingue
      de estresores de los estudiantes de enfermeria en las practicas clinicas. Gac.
      Sanit. 17 (1), 37-51.] at four stages of their studies. The most powerful
      stressors identified by students both at the beginning and at the end of their
      studies were: lack of competence, uncertainty and impotence, being harmed by the
      relationship with patients, emotional involvement, lack of control in
      relationships with patients, contact with suffering, relationships with tutors
      and companions, and overload. Nevertheless, most of the stressors were found to
      lose stressor power during the course of nursing training. The evolution of the
      perception of stressor power and its implications for nurse training are
      discussed, and some recommendations based on our findings are provided.

PMID- 17187907
TI  - Effect of tibial tubercle elevation on biomechanics of the entire knee joint
      under muscle loads.
AB  - BACKGROUND: Anterior elevation of the tibial tubercle, known as Maquet procedure,
      is performed to reduce excessive patellofemoral contact stresses in knee joints
      with patellofemoral osteoarthritis and anterior pain. Previous investigations,
      however, have entirely focused on the likely effect of tibial tubercle elevation
      procedure on biomechanics of contact at the patellofemoral joint with no
      attention what-so-ever to associated alterations in biomechanics of the
      tibiofemoral joint. METHODS: Using a validated 3D nonlinear finite element model
      of the entire knee joint, the effect of 1.25 cm and 2.5 cm tubercle elevations on
      the entire knee joint biomechanics was investigated under constant quadriceps
      load of 411 N alone or combined with hamstrings co-activation of 205.5 N under
      joint angles of 0-90 degrees. FINDINGS: Results confirm the effectiveness of this
      procedure in reducing patellofemoral contact forces, especially at smaller
      flexion angles. Maximum contact stress substantially decreased at full extension
      but increased at 90 degrees. Substantial effects of tuberosity elevation on
      tibial kinematics, cruciate ligament forces, tibiofemoral contact forces and
      extensor lever arm were found. The posterior cruciate ligament and tibiofemoral
      contact forces at larger flexion angles considerably increased whereas the
      anterior cruciate ligament and tibiofemoral contact forces at near full extension
      angles decreased. Overall, the extent of changes depended on the magnitude of
      anterior elevation, joint flexion angle and loading considered. INTERPRETATION:
      Biomechanics of the tibiofemoral joint were significantly influenced by tibial
      tubercle elevation. Current results advocate the need for an integral view of the
      entire knee joint in management of various joint disorders rather than a view in
      which each component is considered and treated in isolation with no due attention
      to perturbations caused and associated consequences.

PMID- 17187908
TI  - A case study of gait compensations for hip muscle weakness in idiopathic
      inflammatory myopathy.
AB  - BACKGROUND: The purpose of this case series was to quantify different strategies
      used to compensate in gait for hip muscle weakness. METHODS: An instrumented gait
      analysis was performed of three females diagnosed with idiopathic inflammatory
      myopathies and compared to a healthy unimpaired subject. Lower extremity joint
      moments obtained from the gait analysis were used to drive an induced
      acceleration model which determined each moment's contribution to upright
      support, forward progression, and hip joint acceleration. FINDINGS: Results
      showed that after midstance, the ankle plantar flexors normally provide upright
      support and forward progression while producing hip extension acceleration. In
      normal gait, the hip flexors eccentrically resist hip extension, but the hip
      flexor muscles of the impaired subjects (S1-3) were too weak to control
      extension. Instead S1-3 altered joint positions and muscle function to produce
      forward progression while minimizing hip extension acceleration. S1 increased
      knee flexion angle to decrease the hip extension effect of the ankle plantar
      flexors. S2 and S3 used either a knee flexor moment or gravity to produce forward
      progression, which had the advantage of accelerating the hip into flexion rather
      than extension, and decreased the demand on the hip flexors. INTERPRETATION:
      Results showed how gait compensations for hip muscle weakness can produce
      independent (i.e. successful) ambulation, although at a reduced speed as compared
      to normal gait. Knowledge of these successful strategies can assist the
      rehabilitation of patients with hip muscle weakness who are unable to ambulate
      and potentially be used to reduce their disability.

PMID- 17187909
TI  - Exceptions to the rule: healthy deprived areas and unhealthy wealthy areas.
AB  - In general, inhabitants of low socio-economic areas are unhealthier than
      inhabitants of high socio-economic areas, but some areas are an exception to this
      rule. These exceptions imply that other factors besides the socio-economic level
      of an area contribute to the health of the inhabitants of an area, e.g.
      environmental factors. In our study we concentrate on areas within the
      Netherlands that are healthier or unhealthier than could be expected based on
      their socio-economic level. This study first identifies these areas and secondly
      determines which area characteristics distinguish these areas from those areas
      where the level of health is in agreement with their socio-economic level. We
      used nation-wide data on neighbourhood differences in population composition
      (gender, age, marital status and ethnicity), urbanisation and two health
      indicators: mortality and hospitalisation rates. In the Netherlands, many areas
      are healthier or unhealthier than could be expected based on their income level
      alone. Areas with higher mortality rates than expected are mainly urban areas
      with high percentages of elderly people and persons living alone. Similar but
      opposite associations are observed for areas with lower mortality rates than
      expected, which are further characterised by a low percentage of non-western
      immigrants. Areas with lower hospitalisation rates than expected are mainly rural
      areas with few non-western immigrants. From these results, we conclude that
      urbanisation and residential segregation based on age, ethnicity and marital
      status might be important contributors to geographical health inequalities.

PMID- 17187910
TI  - Remembering 1500 pictures: the right hemisphere remembers better than the left.
AB  - We hypothesized that the right hemisphere would be superior to the left
      hemisphere in remembering having seen a specific picture before, given its
      superiority in perceptually encoding specific aspects of visual form. A large set
      of pictures (N=1500) of animals, human faces, artifacts, landscapes, and art
      paintings were shown for 2s in central vision, or tachistoscopically (for 100ms)
      in each half visual field, to normal participants who were then tested 1-6 days
      later for their recognition. Images that were presented initially to the right
      hemisphere were better recognized than those presented to the left hemisphere.
      These results, obtained with participants with intact brains, large number of
      stimuli, and long retention delays, are consistent with previously described
      hemispheric differences in the memory of split-brain patients.

PMID- 17187911
TI  - Maintenance electroconvulsive therapy (ECT) for treatment-resistant disorganized
      schizophrenia.
AB  - Patients who have not responded to recommended antipsychotic medications should
      be considered for electroconvulsive therapy (ECT). However, there has been
      controversy about the standardized methods of continuation and maintenance ECT in
      the management of treatment-resistant schizophrenia. We describe a patient with a
      serious case of disorganized schizophrenia who had not responded well with any
      typical and atypical antipsychotic drug for seven years, but responded remarkably
      to acute ECT. Continuation ECT was necessary to sustain a positive therapeutic
      response. The patient showed dramatic improvement from 70 to 20 in the 18-item
      Brief Psychiatric Rating Scale (BPRS) score (71% reduction) after acute ECT and
      continuation ECT. Using maintenance ECT, she was able to live in the custody of
      her parents after 7-years hospitalization. This case report suggests that
      continuation and maintenance ECT benefits patients with serious cases of
      refractory schizophrenia.

PMID- 17187912
TI  - Analysis of genotoxic potentiality of stevioside by comet assay.
AB  - Stevioside is a natural non-caloric sweetener extracted from Stevia rebaudiana
      (Bertoni) leaves. It has been widely used in many countries, including Japan,
      Korea, China, Brazil and Paraguay, either as a substitute for sucrose in
      beverages and foods or as a household sweetener. The aim of this work was to
      study its genotoxic potentiality in eukaryotic cells. Wistar rats were treated
      with stevioside solution (4mg/mL) through oral administration (ad libitum) and
      the DNA-induced damage was evaluated using the single cell gel electrophoresis
      (comet assay). The results showed that treatment with stevioside generates
      lesions in peripheral blood, liver, brain and spleen cells in different levels,
      the largest effect being in liver. Therefore, these undesired effects must be
      better understood, once the data present here point to possible stevioside
      mutagenic properties.

PMID- 17187913
TI  - Carcinogenesis studies of benzophenone in rats and mice.
AB  - Benzophenone, an aryl ketone, is used primarily as a photoinitiator and fragrance
      enhancer. Groups of 50 male and 50 female F344 rats and B6C3 F1 mice were fed
      diets containing 0, 312, 625, and 1250 ppm benzophenone for 105 weeks. Survival
      of males exposed to 1250 ppm benzophenone was significantly less than that of
      controls. There was a positive trend in the incidence of renal tubule adenoma in
      male rats; these neoplasms were accompanied by significantly increased incidences
      of renal tubule hyperplasia. Increased incidences of mononuclear cell leukemia
      were observed in male rats exposed to 312 or 625 ppm benzophenone and in female
      rats exposed to 625 ppm benzophenone. Liver lesions observed included
      significantly increased incidences of hepatocytic centrilobular hypertrophy in
      all exposed groups of rats. In mice, survival of all exposed groups was generally
      similar to that of the control groups. In male mice, there were significantly
      increased incidences of hepatocellular adenoma in the 625 and 1250 ppm groups. In
      female mice, the incidences of hepatocellular adenoma in the 625 and 1250 ppm
      groups were higher than expected after adjusting for the lower body weights in
      these groups. The incidences of kidney nephropathy in exposed groups of female
      mice, as well as the severity of nephropathy in exposed groups of males, were
      significantly increased. The incidences of metaplasia of the olfactory epithelium
      were significantly increased in 1250 ppm mice. Rare histiocytic sarcomas were
      observed in female rats and mice in the 625 and 1250 ppm groups. Under the
      conditions of these 2-year studies, there was some evidence of carcinogenic
      activity of benzophenone in male F344/N rats based on increased incidences of
      renal tubule adenoma. There was equivocal evidence of carcinogenic activity of
      benzophenone in female F344/N rats based on the marginal increased incidences of
      mononuclear cell leukemia and histiocytic sarcoma. There was some evidence of
      carcinogenic activity of benzophenone in male B6C3F(1) mice based on increased
      incidences of hepatocellular neoplasms, primarily adenoma. There was some
      evidence of carcinogenic activity of benzophenone in female B6C3F(1) mice based
      on increased incidences of histiocytic sarcoma; the incidences of hepatocellular
      adenoma in female B6C3F(1) mice may have been related to benzophenone exposure.

PMID- 17187916
TI  - Modifications to advanced life support in renal failure.
AB  - The outcome of cardiopulmonary resuscitation (CPR) has been reported to be worse
      in patients with renal failure compared with those with normal renal function. It
      is likely that this increased mortality may be at least partly attributable to
      sub-optimal and highly variable treatment strategies used in cardiac arrest in
      patients with renal failure, but this issue has not previously been explored.
      Such patients undoubtedly pose a challenge to advanced life support (ALS)
      providers, and renal unit staff are not trained to provide specialist advice
      after a patient has sustained a cardiac arrest. There are few studies
      investigating the epidemiology, safety or outcome of cardiac arrest in patients
      with renal failure and there are no generally accepted resuscitation guidelines
      for this special circumstance. In this article we discuss the unique problems of
      resuscitating patients with renal failure and propose a suitable management
      strategy.

PMID- 17187915
TI  - Toxicokinetics and toxicity of thioacetamide sulfoxide: a metabolite of
      thioacetamide.
AB  - Thioacetamide (TA) is bioactivated by CYP2E1 to TA sulfoxide (TASO), and to the
      highly reactive sulfdioxide (TASO(2)), which initiates hepatic necrosis by
      covalent binding. Previously, we have established that TA exhibits saturation
      toxicokinetics over a 12-fold dose range, which explains the lack of dose
      response for bioactivation-based liver injury. In vivo and in vitro studies
      indicated that the second step (TASO-->TASO(2)) of TA bioactivation is less
      efficient than the first one (TA-->TASO). The objective of the present study was
      to specifically test the saturation of the second step of TA bioactivation by
      directly administering TASO, which obviates the contribution from first step,
      i.e. TA-->TASO. Male SD rats were injected with low (50mg/kg, ip), medium
      (100mg/kg) and high (LD(70), 200mg/kg) doses of TASO. Bioactivation-mediated
      liver injury that occurs in the initial time points (6 and 12h), estimated by
      plasma ALT, AST and liver histopathology over a time course, was not dose
      proportional. Escalation of liver injury thereafter was dose dependent: low dose
      injury subsided; medium dose injury escalated upto 36h before declining; high
      dose injury escalated from 24h leading to 70% mortality. TASO was quantified in
      plasma by HPLC at various time points after administration of the three doses.
      With increasing dose (i.e., from 50 to 200mg/kg), area under the curve (AUC) and
      C(max) increased more than dose proportionately, indicating that TASO
      bioactivation exhibits saturable kinetics. Toxicokinetics and initiation of liver
      injury of TASO are similar to that of TA, although TASO-initiated injury occurs
      at lower doses. These findings indicate that bioactivation of TASO to its
      reactive metabolite is saturable in the rat as suggested by previous studies with
      TA.

PMID- 17187917
TI  - Unilateral absence of tube and ovary with renal agenesis and associated pyloric
      stenosis: communication.

PMID- 17187914
TI  - Canavanine content in sword beans (Canavalia gladiata): analysis and effect of
      processing.
AB  - The amino acid canavanine is a potentially toxic constituent of leguminous seeds.
      The aim of the present study was to determine the ability of different processing
      methods to reduce canavanine in sword beans (Canavalia gladiata). For this
      purpose a method for the detection and quantification of canavanine was developed
      using reversed-phase high-performance liquid chromatography of the dabsylated
      derivatives. The recovery of canavanine using this method was 88-91%. Optimum
      extraction of canavanine from raw and processed beans was obtained by addition of
      hot water prior to overnight soaking. The results obtained with this method agree
      well with previously published values for raw seeds. The method is sensitive,
      specific and can successfully be applied to the detection of canavanine in
      legumes. Overnight soaking and boiling in excess water followed by decanting gave
      the most pronounced reduction in canavanine content (around 50%), followed by
      boiling and decanting excess water (34%). Roasting as used in this study and
      autoclaving were less effective in reducing the canavanine content.

PMID- 17187918
TI  - An uncomplicated pregnancy associated with Sturge-Weber angiomatosis.

PMID- 17187919
TI  - Future carbon balance of China's forests under climate change and increasing CO2.
AB  - The possible response of the carbon (C) balance of China's forests to an increase
      in atmospheric CO(2) concentration and climate change was investigated through a
      series of simulations using the Integrated Terrestrial Ecosystem Carbon (InTEC)
      model, which explicitly represents the effects of climate, CO(2) concentration,
      and nitrogen deposition on future C sequestration by forests. Two climate change
      scenarios (CGCM2-A2 and -B2) were used to drive the model. Simulations showed
      that China's forests were a C sink in the 1990 s, averaging 189 Tg C yr(-1)
      (about 13% of the global total). This sink peaks around 2020 and then gradually
      declines to 33.5 Tg C yr(-1) during 2091-2100 without climate and CO(2) changes.
      Effects of pure climate change of CGCM2-A2 and -B2 without allowing CO(2) effects
      on C assimilation in plants might reduce the average net primary productivity
      (NPP) of China's forests by 29% and 18% during 2091-2100, respectively. Total
      soil C stocks might decrease by 16% and 11% during this period. China's forests
      might broadly act as C sources during 2091-2100, with values of about 50 g Cm(
      2)yr(-1) under the moderate warming of CGCM2-B2 and 50-200 g Cm(-2)yr(-1) under
      the warmer scenario of CGCM2-A2. An increase in CO(2) might broadly increase
      future C sequestration of China's forests. However, this CO(2) fertilization
      effect might decline with time. The CO(2) fertilization effects on NPP by the end
      of this century are 349.6 and 241.7 Tg C yr(-1) under CGCM2-A2 and -B2 increase
      scenarios, respectively. These effects increase by 199.1 and 126.6 Tg C yr(-1) in
      the first 50 years, and thereafter, by 150.5 and 115.1 Tg C yr(-1) in the second
      50 years under CGCM2-A2 and -B2 increase scenarios, respectively. Under a CO(2)
      increase without climate change, the majority of China's forests would be C sinks
      during 2091-2100, ranging from 0 to 100 g Cm(-2)yr(-1). The positive effect of
      CO(2) fertilization on NPP and net ecosystem productivity would be exceeded by
      the negative effect of climate change after 2050. Under the CGCM2-A2 climate
      scenario and with direct CO(2) effects, China's forests may be a small C source
      of 7.6 Tg C yr(-1) during 2091-2100. Most forests act as C sources of 0-40 g Cm(
      2)yr(-1). Under the CGCM2-B2 climate scenario and with direct CO(2) effects,
      China's forests might be a small C sink of 10.5 Tg C yr(-1) during 2091-2100,
      with C sequestration of most forests ranging from 0 to 40 g Cm(-2)yr(-1). Stand
      age structure plays a more dominant role in determining future C sequestration
      than CO(2) and climate change. The prediction of future C sequestration of
      China's forests is very sensitive to the Q(10) value used to estimate maintenance
      respiration and to soil water availability and less sensitive to N deposition
      scenario. The results are not yet comprehensive, as no forest disturbance data
      were available or predicted after 2001. However, the results indicate a range of
      possible responses of the C balance of China's forests to various scenarios of
      increase in CO(2) and climate change. These results could be useful for assessing
      measures to mitigate climate change through reforestation.

PMID- 17187921
TI  - Wood carbon content of tree species in Eastern China: interspecific variability
      and the importance of the volatile fraction.
AB  - Data on the mass density and carbon content of tree organs, and in particular
      stem wood, are essential for accurate assessments of forest carbon sequestration.
      However most available data, including that for East Asia, has neglected the
      volatile C fraction. Wood samples were collected and assayed for C content from
      14 native tree species in Jilin Province, NE China. C content showed
      statistically significant variation among species, ranging from 48.4% to 51.0%.
      The volatile C fraction was non-negligible, averaging 2.2%, and showed high
      variation among species. As found in prior studies, wood C content was
      appreciably higher in conifer than hardwood (angiosperm) species (50.8+/-0.1% vs.
      49.5+/-0.2%, respectively). Wood carbon density (gC/cm(3)) showed very high inter
      specific variation, due mainly to differences in wood specific gravity. Our
      analyses, in conjunction with recently published data from North America,
      indicate a global mean value of 47.5+/-0.5% wood C content exclusive of volatile
      C; the widely used 50% figure corresponds more closely to total wood C inclusive
      of the volatile fraction. Failure to include volatile C or to use species- or
      higher-taxon-specific C content values in forest C assessments is likely to
      introduce biases on the order approximately 4-6%. In addition, the stocks and
      flows of the volatile C fraction in wood are in themselves an important and
      sorely neglected aspect of forest C processes likely to be strongly impacted by
      harvests and other management practices.

PMID- 17187920
TI  - Effects of topography on simulated net primary productivity at landscape scale.
AB  - Local topography significantly affects spatial variations of climatic variables
      and soil water movement in complex terrain. Therefore, the distribution and
      productivity of ecosystems are closely linked to topography. Using a coupled
      terrestrial carbon and hydrological model (BEPS-TerrainLab model), the
      topographic effects on the net primary productivity (NPP) are analyzed through
      four modelling experiments for a 5700 km(2) area in Baohe River basin, Shaanxi
      Province, northwest of China. The model was able to capture 81% of the
      variability in NPP estimated from tree rings, with a mean relative error of 3.1%.
      The average NPP in 2003 for the study area was 741 gCm(-2)yr(-1) from a model run
      including topographic effects on the distributions of climate variables and
      lateral flow of ground water. Topography has considerable effect on NPP, which
      peaks near 1350 m above the sea level. An elevation increase of 100 m above this
      level reduces the average annual NPP by about 25 gCm(-2). The terrain aspect
      gives rise to a NPP change of 5% for forests located below 1900 m as a result of
      its influence on incident solar radiation. For the whole study area, a simulation
      totally excluding topographic effects on the distributions of climatic variables
      and ground water movement overestimated the average NPP by 5%.

PMID- 17187922
TI  - On the common growth of the European association of urology annual meeting and of
      European urology, "your" platinum journal.

PMID- 17187923
TI  - Functional significance of using tissue adhesive substance in nephron-sparing
      surgery: assessment by quantitative SPECT of 99m Tc-Dimercaptosuccinic acid
      scintigraphy.
AB  - OBJECTIVES: To compare changes in renal function following nephron-sparing
      surgery (NSS) using tissue adhesive only versus NSS using standard suturing
      technique, as measured by quantitative SPECT of 99m Tc-dimercaptosuccinic acid
      uptake by the kidney (QDMSA). MATERIALS AND METHODS: QDMSA was done before and 3
      6 mo after the operation in 32 patients who underwent standard suturing technique
      and in 24 patients in whom tissue adhesive sealant (19 with albumin
      glutaraldehyde tissue adhesive [BioGlue]; 5 with CoSeal) was used to close the
      parenchymal defect. Individual kidney uptake was measured and retrospectively
      compared between the two groups. RESULTS: Average tumor diameter was 3.4cm
      (range: 2.2-6) in the suture group and 3.56 (range: 1.7-6) in the tissue sealant
      group. In the tissue sealant group following surgery, we observed an average
      individual renal function loss of 11.49% compared with the suture group in whom
      an average individual renal function loss of 20.36% (p = 0.02) was measured by
      99m Tc-DMSA. CONCLUSIONS: The use of tissue sealant to close the parenchymal
      defect during NSS demonstrated a statistically significant advantage in reducing
      functioning renal loss as measured by the absolute uptake of QDMSA. Further
      clinical studies are required to establish the role of tissue sealants in NSS.

PMID- 17187924
TI  - Ghost resonance in a pool of heterogeneous neurons.
AB  - We numerically study the subharmonic response of a heterogeneous pool of neurons
      to a pair of independent inputs. The neurons are stimulated with periodic pulse
      trains of frequencies f(1)=2 Hz and f(2)=3 Hz, and with inharmonic pulses whose
      frequencies f(1) and f(2) are equally shifted an amount Delta f. When both inputs
      are subthreshold, we find that the neurons respond at a frequency equal to f(2)
      f(1) in the harmonic situation (Delta f=0), that increases linearly with Delta f
      in the inharmonic case. Thus the neurons detect a frequency not present in the
      input; this effect is termed "ghost resonance". When one of the inputs is
      slightly suprathreshold the ghost resonance persists, but responses related with
      the frequency of the suprathreshold input also emerge. This behavior must be
      taken into account in experimental studies of signal integration and coincidence
      detection by neuronal pools.

PMID- 17187925
TI  - Cooperative actions between myosin heads bring effective functions.
AB  - A recent study with single molecule measurements has reported that muscle myosin,
      a molecular motor, stochastically generates multiple steps along an actin
      filament associated with the hydrolysis of a single ATP molecule [Kitamura, K.,
      Tokunaga, M., Esaki, S., Iwane, A.H., Yanagida, T., 2005. Mechanism of muscle
      contraction based on stochastic properties of single actomyosin motors observed
      in vitro. Biophysics 1, 1-19]. We have built a model reproducing such a
      stochastic movement of a myosin molecule incorporated with ATPase reaction cycles
      and demonstrated that the thermal fluctuation was a key for the function of
      myosin molecules [Esaki, S., Ishii, Y., Yanagida, T., 2003. Model describing the
      biased Brownian movement of myosin. Proc. Jpn. Acad. 79 (Ser B), 9-14]. The size
      of the displacement generated during the hydrolysis of single ATP molecules was
      limited within a half pitch of an actin filament when a single myosin molecules
      work separately. However, in muscle the size of the displacement has been
      reported to be greater than 60 nm [Yanagida, T., Arata, T., Oosawa, F., 1985.
      Sliding distance of actin filament induced by a myosin crossbridge during one ATP
      hydrolysis cycle. Nature 316, 366-369; Higuchi et al., 1991]. The difference
      suggests cooperative action between myosin heads in muscle. Here we extended the
      model built for an isolated myosin head to a system in which myosin heads are
      aligned in muscle arrangement to understand the cooperativity between heads. The
      simulation showed that the rotation of the actin filament [Takezawa, Y.,
      Sugimoto, Y., Wakabayashi, K., 1998. Extensibility of the actin and myosin
      filaments in various states of skeletal muscles as studied by X-ray diffraction.
      Adv. Exp. Med. Biol. 453, 309-317; Wakabayashi, K., Ueno, Y., Takezawa, Y.,
      Sugimoto, Y., 2001. Muscle contraction mechanism: use of X-ray synchrotron
      radiation. Nat. Enc. Life Sci. 1-11] associated with the release of ATPase
      products and binding of ATP as well as interaction between myosin heads allowed
      the myosin filament to move greater than a half pitch of the actin filament while
      a single ATP molecule is hydrolyzed. Our model demonstrated that the movement is
      loosely coupled to the ATPase cycle as observed in muscle.

PMID- 17187926
TI  - Getting into shape: optimal ligand gradients for axonal guidance.
AB  - During neural development, neurons from downstream, presynaptic regions of the
      nervous system (such as the retina) send spatially patterned axonal projections
      to upstream, target regions (the tectum or superior colliculus). A servomechanism
      model has been proposed to explain the pattern and time-course of axonal growth
      between these two regions [Honda, H., 1998. Topographic mapping in the
      retinotectal projection by means of complementary ligand and receptor gradients:
      a computer simulation study. J. Theor. Biol., 192, 235-246]. Here, we show that a
      modification of this model incorporating a different criterion for axonal
      decision-making, called the local optimum rule, is guaranteed to converge to a
      topographic map under a wide range of conditions encountered during neural
      development. A theoretical investigation of these conditions leads to new
      hypotheses regarding map formation.

PMID- 17187927
TI  - Brownian motion, fluctuation and life.
AB  - The measurements of dynamic behaviors of biomolecules in relation to their
      functions have been allowed using single molecule measurements. Thermal Brownian
      motion causes random step motion of motor proteins and structural fluctuation of
      protein molecules between multiple states. In hierarchic structure of life, the
      fluctuation is modulated. Random fluctuation is biased to directional motion and
      reactions as a result of interaction of proteins. The fluctuation of kinetic
      state of signaling proteins results in polarization and localization of cells. A
      recognition process in brain is also explained by the equation analogous to
      biochemical reaction at the molecular level. Thus dynamic processes originated
      from thermal motion may play an important role in activation processes in life.

PMID- 17187928
TI  - Pituitary stalk hemangioblastoma: the fourth case report and review of the
      literature.
AB  - Supratentorial hemangioblastomas (HBL) have been rarely described in the
      literature. Herein we report the fourth case of pituitary stalk HBL diagnosed
      concurrently with cerebellar HBLs in a 51-year-old woman with von Hippel-Lindau
      disease. Complete resection of the lesion was achieved using left frontopterional
      craniotomy and no recurrence was observed after 8 years of follow-up. The
      clinical presentation, radiological features, pathological findings, and the
      management of this particular case are discussed in the light of the available
      literature. To our knowledge, this case is the only pituitary stalk HBL with
      total resection, and a long follow-up fully documented.

PMID- 17187930
TI  - Effects of high hydrostatic pressure on embryonation of Ascaris suum eggs.
AB  - High hydrostatic pressure processing (HPP) has been shown to be an effective non
      thermal means of inactivating microorganisms from various food products. Little
      information is available regarding the effects of HPP on metazoan parasites.
      Outbreaks of food-borne disease have been associated with importation of food
      contaminated with fecal material. Ascaris suum is used as a surrogate model
      metazoan parasite for the human roundworm, Ascaris lumbricoides, to study the
      effects of treatments on the inactivation of eggs in sludge. The present study
      was conducted to determine the effects of HPP on A. suum eggs. Unembryonated A.
      suum eggs were subjected to 138-552 megapascals (MPa) for 10-60s in a commercial
      HPP unit. Embryonation was induced after HPP treatments by incubating eggs in
      0.01N sulfuric acid at room temperature. After 21 days, 100 eggs were examined
      per treatment using a light microscope and the percent of embryonated eggs was
      determined. Embryonation was induced in 38-76% eggs that were subjected to 138
      and 270MPa. No embryonation was observed in eggs exposed to pressures of 241MPa
      or more for 60s or in eggs exposed to 276MPa for 10-30s. These results indicate
      that HPP treatment could be used to protect contaminated food items by
      inactivating A. suum eggs and may also have potential in reducing food-borne
      illness resulting from fecal contamination.

PMID- 17187929
TI  - Exposure to cell phone radiation up-regulates apoptosis genes in primary cultures
      of neurons and astrocytes.
AB  - The health effects of cell phone radiation exposure are a growing public concern.
      This study investigated whether expression of genes related to cell death
      pathways are dysregulated in primary cultured neurons and astrocytes by exposure
      to a working Global System for Mobile Communication (GSM) cell phone rated at a
      frequency of 1900MHz. Primary cultures were exposed to cell phone emissions for
      2h. We used array analysis and real-time RT-PCR to show up-regulation of caspase
      2, caspase-6 and Asc (apoptosis associated speck-like protein containing a card)
      gene expression in neurons and astrocytes. Up-regulation occurred in both "on"
      and "stand-by" modes in neurons, but only in "on" mode in astrocytes.
      Additionally, astrocytes showed up-regulation of the Bax gene. The effects are
      specific since up-regulation was not seen for other genes associated with
      apoptosis, such as caspase-9 in either neurons or astrocytes, or Bax in neurons.
      The results show that even relatively short-term exposure to cell phone
      radiofrequency emissions can up-regulate elements of apoptotic pathways in cells
      derived from the brain, and that neurons appear to be more sensitive to this
      effect than astrocytes.

PMID- 17187931
TI  - Combined use of free and pedicled skin flaps for the reconstruction of
      extremities in high voltage electrical injury.

PMID- 17187932
TI  - Neuronal activity in the primary visual cortex of the cat freely viewing natural
      images.
AB  - Many studies have now demonstrated that neurons in the visual cortex of cats and
      monkeys change their activity when stimuli are presented beyond their classical
      receptive field, and that these responses are not readily apparent from their
      receptive field properties. However few studies have been conducted to
      investigate the discharge properties of neurons in the visual cortex of animals
      when they are allow to freely view natural images. We employ tetrodes, which
      enable simultaneous and separable recordings of small numbers of neighboring
      neurons, to record 102 single units from 59 sites from areas 17 and 18 of two
      alert cats. While the animals viewed either natural images or black screens, they
      made frequent saccadic eye movements and gaze fixations. Fixations onto an
      image's location increased neuronal firing peaking at 80-100 ms after the
      fixation onset, to then decrease steadily with time despite continuous fixation.
      Saccades trigger a fast decrease in firing rate for both images and darkness.
      When we examined the incidence of correlated firing, we observed significant
      synchrony during the initial phases of visual fixations when the animals viewed
      natural scenes. Such synchrony was absent during saccadic eye movements and
      during eye movements in darkness. Our data revealed that scanning of natural
      scenes is associated with a rapid succession of distinct fixation-related
      activation patterns that included transient rate changes and excess coincident
      firing. The transient nature of these synchronization phenomena suggests a fast
      acting mechanism, which is in good agreement with the evidence that basic
      operations of scene analysis must be accomplished within a few tens of
      milliseconds in primary visual cortex.

PMID- 17187933
TI  - An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's
      disease pathology following closed head injury: evidence of pharmacogenomic
      interaction.
AB  - Apolipoprotein E (apoE) modifies glial activation and the CNS inflammatory
      response in an isoform-specific manner. Peptides derived from the receptor
      binding region of apoE have been demonstrated to maintain the functional activity
      of the intact protein, and to improve histological and functional deficits after
      closed head injury. In the current study, APOE2, APOE3, and APOE4 targeted
      replacement (TR) mice expressing the human apoE protein isoforms (apoE2, apoE3
      and apoE4) were used in a clinically relevant model of closed head injury to
      assess the interaction between the humanized apoE background and the therapeutic
      apoE mimetic peptide, apoE(133-149). Treatment with the apoE-mimetic peptide
      reduced microglial activation and early inflammatory events in all of the
      targeted replacement animals and was associated with histological and functional
      improvement in the APOE2TR and APOE3TR animals. Similarly, brain beta amyloid
      protein (Abeta)(1-42) levels were increased as a function of head injury in all
      of the targeted replacement mice, while treatment with apoE peptide suppressed
      Abeta(1-42) levels in the APOE2TR and APOE3TR animals. These results suggest a
      pharmacogenomic interaction between the therapeutic effects of the apoE mimetic
      peptide and the human apoE protein isoforms. Furthermore, they suggest that
      administration of apoE-mimetic peptides may serve as a novel therapeutic strategy
      for the treatment of acute and chronic neurological disease.

PMID- 17187934
TI  - Alterations in dopamine D3 receptors in the circling (ci3) rat mutant.
AB  - We have previously described a black-hooded mutant rat (BH.7A/Ztm-ci3/ci3) that
      displays abnormal lateralized circling behavior, but normal auditory and
      vestibular functions. Neurochemical determination of dopamine and dopamine
      metabolite levels in striatum, nucleus accumbens and substantia nigra showed that
      ci3 rats have a significant asymmetry in striatal dopamine in that dopamine
      levels were significantly lower in the hemisphere contralateral to the preferred
      direction of turning. Consistent with this finding, immunohistological
      examination of dopaminergic neurons in substantia nigra and ventral tegmental
      area yielded a significant laterality in the medial part of substantia nigra pars
      compacta with a lower density of tyrosine hydroxylase-positive neurons in the
      contralateral hemisphere of mutant circling rats, while no laterality was seen in
      unaffected rats of the background strain. In the present study, quantitative
      autoradiography was used to examine the binding of [(3)H]SCH 23390,
      [(3)H]raclopride and [(3)H]7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin)
      to dopamine D1, D2, and D3 receptors, respectively, in various brain regions of
      ci3 rats and unaffected rats of the background strain (BH.7A(LEW)/Won). No
      significant differences between circling rats and controls were obtained for D1
      and D2 receptor binding in any region, but mutant rats differed from controls in
      dopamine D3 binding in several regions. A significant decrease in D3 binding was
      seen in the shell of the nucleus accumbens, the islands of Calleja, and the
      subependymal zone of ci3 mutant rats. Furthermore, a significant laterality in D3
      binding was determined in ci3 rats in that binding was lower in the contralateral
      hemisphere in the shell of the nucleus accumbens and the islands of Calleja. Our
      data indicate that alterations of dopamine D3 receptors may be involved in the
      behavioral phenotype of the ci3 rat, thus substantiating the findings from a
      recent genetic linkage analysis that indicated the D3 receptor gene as a
      candidate gene in this rat mutant.

PMID- 17187935
TI  - Progesterone and its derivatives are neuroprotective agents in experimental
      diabetic neuropathy: a multimodal analysis.
AB  - One important complication of diabetes is damage to the peripheral nervous
      system. However, in spite of the number of studies on human and experimental
      diabetic neuropathy, the current therapeutic arsenal is meagre. Consequently, the
      search for substances to protect the nervous system from the degenerative effects
      of diabetes has high priority in biomedical research. Neuroactive steroids might
      be interesting since they have been recently identified as promising
      neuroprotective agents in several models of neurodegeneration. We have assessed
      whether chronic treatment with progesterone (P), dihydroprogesterone (DHP) or
      tetrahydroprogesterone (THP) had neuroprotective effects against streptozotocin
      (STZ)-induced diabetic neuropathy at the neurophysiological, functional,
      biochemical and neuropathological levels. Using gas chromatography coupled to
      mass-spectrometry, we found that three months of diabetes markedly lowered P
      plasma levels in male rats, and chronic treatment with P restored them, with
      protective effects on peripheral nerves. In the model of STZ-induced of diabetic
      neuropathy, chronic treatment for 1 month with P, or with its derivatives, DHP
      and THP, counteracted the impairment of nerve conduction velocity (NCV) and
      thermal threshold, restored skin innervation density, and improved Na(+),K(+)
      ATPase activity and mRNA levels of myelin proteins, such as glycoprotein zero and
      peripheral myelin protein 22, suggesting that these neuroactive steroids, might
      be useful protective agents in diabetic neuropathy. Interestingly, different
      receptors seem to be involved in these effects. Thus, while the expression of
      myelin proteins and Na(+),K(+)-ATPase activity are only stimulated by P and DHP
      (i.e. two neuroactive steroids interacting with P receptor, PR), NCV, thermal
      nociceptive threshold and intra-epidermal nerve fiber (IENF) density are also
      affected by THP, which interacts with GABA-A receptor. Because, a therapeutic
      approach with specific synthetic receptor ligands could avoid the typical side
      effects of steroids, future experiments will be devoted to evaluating the role of
      PR and GABA-A receptor in these protective effects.

PMID- 17187937
TI  - A common target for calorie restriction and photodynamic therapy: EPR mapping ROS
      signaling network at organismic level.

PMID- 17187938
TI  - Inhibition of HMGB1 by deep ocean water attenuates endotoxin-induced sepsis.

PMID- 17187936
TI  - Estimates of prenatal abstinence from alcohol: a matter of perspective.
AB  - Abstinence from alcohol has been recommended for both pregnant and pre
      conceptional women. The purpose of this study is to compare self and partner
      reports of abstinence from alcohol in a sample of 253 pregnant women who were T
      ACE (Tolerance, Annoy, Cut-down, Eye-opener) alcohol screen positive. Dyads'
      reports of the women's abstinence from alcohol before, during, and after
      pregnancy were compared. Based on their own self-report, less than 20% of the
      pregnant women were abstinent in their first trimester and about half were
      abstinent for the rest of their pregnancy. Partners significantly over-estimated
      the women's abstinence from alcohol at all points except in the post-partum
      period when the dyad had the highest rate of agreement (85.4%). Reasons for the
      discrepancies in the self and partner reports of prenatal abstinence, and how
      partners might influence such behavior remain speculative, but identify areas for
      future research and prevention.

PMID- 17187939
TI  - Central neurocytoma: management recommendations based on a 35-year experience.
AB  - PURPOSE: To examine the outcomes of patients with histologically confirmed
      central neurocytomas. METHODS AND MATERIALS: The data from 45 patients with
      central neurocytomas diagnosed between 1971 and 2003 were retrospectively
      evaluated. Various combinations of surgery, radiotherapy (RT), and chemotherapy
      had been used for treatment. RESULTS: The median follow-up was 10.0 years. The 10
      year overall survival and local control rate was 83% and 60%, respectively.
      Patients whose tumor had a mitotic index of <3 (per 10 high-power fields)
      experienced a 10-year survival and local control rate of 89% and 74%,
      respectively, compared with 57% (p = 0.040) and 46% (p = 0.14) for patients with
      a tumor mitotic index of > or =3. The 10-year survival and local control rate was
      90% and 74% for patients with typical tumors compared with 63% (p = 0.055) and
      46% (p = 0.41) for those with atypical tumors. A comparison of gross total
      resection with subtotal resection showed no significant difference in survival or
      local control. Postoperative RT improved local control at 10 years (75% with RT
      vs. 51% without RT, p = 0.045); however, this did not translate into a survival
      benefit. No 1p19q deletions were found in the 19 tumors tested. CONCLUSION:
      Although the overall prognosis is quite favorable, one-third of patients
      experienced tumor recurrence or progression at 10 years, regardless of the extent
      of the initial resection. Postoperative RT significantly improved local control
      but not survival, most likely because of the effectiveness of salvage RT. For
      incompletely resected atypical tumors and/or those with a high mitotic index,
      consideration should be given to adjuvant RT because of the more aggressive
      nature.

PMID- 17187940
TI  - Multi-institutional clinical experience with the Calypso System in localization
      and continuous, real-time monitoring of the prostate gland during external
      radiotherapy.
AB  - PURPOSE: To report the clinical experience with an electromagnetic treatment
      target positioning and continuous monitoring system in patients with localized
      prostate cancer receiving external beam radiotherapy. METHODS AND MATERIALS: The
      Calypso System is a target positioning device that continuously monitors the
      location of three implanted electromagnetic transponders at a rate of 10 Hz. The
      system was used at five centers to position 41 patients over a full course of
      therapy. Electromagnetic positioning was compared to setup using skin marks and
      to stereoscopic X-ray localization of the transponders. Continuous monitoring was
      performed in 35 patients. RESULTS: The difference between skin mark vs. the
      Calypso System alignment was found to be >5 mm in vector length in more than 75%
      of fractions. Comparisons between the Calypso System and X-ray localization
      showed good agreement. Qualitatively, the continuous motion was unpredictable and
      varied from persistent drift to transient rapid movements. Displacements > or =3
      and > or =5 mm for cumulative durations of at least 30 s were observed during 41%
      and 15% of sessions. In individual patients, the number of fractions with
      displacements > or =3 mm ranged from 3% to 87%; whereas the number of fractions
      with displacements > or =5 mm ranged from 0% to 56%. CONCLUSION: The Calypso
      System is a clinically efficient and objective localization method for
      positioning prostate patients undergoing radiotherapy. Initial treatment setup
      can be performed rapidly, accurately, and objectively before radiation delivery.
      The extent and frequency of prostate motion during radiotherapy delivery can be
      easily monitored and used for motion management.

PMID- 17187941
TI  - Comparison of inverse-planned three-dimensional conformal radiotherapy and
      intensity-modulated radiotherapy for non-small-cell lung cancer.
AB  - PURPOSE: Lungs are the major dose-limiting organ during radiotherapy (RT) for non
      small-cell lung cancer owing to the development of pneumonitis. This study
      compared intensity-modulated RT (IMRT) with three-dimensional conformal RT (3D
      CRT) in reducing the dose to the lungs. METHODS: Ten patients with localized non
      small-cell lung cancer underwent computed tomography (CT). The planning target
      volume (PTV) was defined and the organs at risk were outlined. An inverse
      planning program, AutoPlan, was used to design the beam angle-optimized six-field
      noncoplanar 3D-CRT plans. Each 3D-CRT plan was compared with a series of five
      IMRT plans per patient. The IMRT plans were created using a commercial algorithm
      and consisted of a series of three, five, seven, and nine equidistant coplanar
      field arrangements and one six-field noncoplanar plan. The planning objectives
      were to minimize the lung dose while maintaining the dose to the PTV. The
      percentage of lung volume receiving >20 Gy (V20) and the percentage of the PTV
      covered by the 90% isodose (PTV90) were the primary endpoints. The PTV90/V20
      ratio was used as the parameter accounting for both the reduction in lung volume
      treated and the PTV coverage. RESULTS: All IMRT plans, except for the three-field
      coplanar plans, improved the PTV90/V20 ratio significantly compared with the
      optimized 3D-CRT plan. Nine coplanar IMRT beams were significantly better than
      five or seven coplanar IMRT beams, with an improved PTV90/V20 ratio. CONCLUSION:
      The results of our study have shown that IMRT can reduce the dose to the lungs
      compared with 3D-CRT by improving the conformity of the plan.

PMID- 17187942
TI  - Antinociceptive activity of Helicteres isora.
AB  - Helicteres isora root extracts were studied for antinociceptive activity on
      acetic acid-induced writhing test in mice, at a dose of 250 mg/kg. Petroleum
      ether, chloroform and aqueous ethanol extracts have shown significant activity.

PMID- 17187943
TI  - An exploration of 3'-end processing signals and their tissue distribution in
      Oryza sativa.
AB  - The 3' untranslated regions deeply affect many properties of eukaryotic mRNA. In
      plants, the polyadenine control signals contained in these regions seem to be
      more variable than of mammals. Three cDNA libraries derived from the leaf,
      endosperm and stem tissues of rice were sequenced from the 3'-end. Of the 9911
      transcripts analyzed, 5723 unique transcripts were identified from the leaf
      sequences, 2934 from the endosperm and 1254 from the stem. The information
      entropy and two statistical methods were used to compile a list of rice poly(A)
      control signals. Based on their distribution, these signals can be roughly
      grouped into far-upstream element (FUE), near-upstream element (NUE), T-rich
      region (TRE) and downstream element (DE). The distribution of rice conserved
      regions is similar to the previous model from Arabidopsis and yeast, with a few
      differences in word constructions. Interestingly, we also found the word
      distributions were diverse in the cleavage site of downstream sequences of
      different rice tissues. The signal bias in downstream sequences may lead mRNA to
      be differently cleaved in different rice tissues.

PMID- 17187944
TI  - Cloning and expression of Rift Valley fever virus nucleocapsid (N) protein and
      evaluation of a N-protein based indirect ELISA for the detection of specific IgG
      and IgM antibodies in domestic ruminants.
AB  - Serodiagnosis of Rift Valley fever (RVF) currently relies on the use of live or
      inactivated whole virus as antigens. The recombinant nucleocapsid (N) protein of
      RVF virus was tested for diagnostic applicability in an indirect enzyme-linked
      immunosorbent assay (I-ELISA), using sera from experimentally infected sheep
      (n=128), vaccinated sheep (n=240), and field-collected sera from sheep (n=251),
      goats (n=362) and cattle (n=100). The N-protein based I-ELISA performed at least
      as good as VN and HI tests. In goat the diagnostic sensitivity (D-Sn) and
      specificity (D-Sp) of the I-ELISA was 100% when using the anti-species IgG
      conjugate. Using protein G as a detection system, the D-Sn and D-Sp in goats were
      99.4% and 99.5%, in sheep field sera both 100%, in cattle 100% and 98.3%,
      respectively. The I-ELISA based on recombinant N-protein has the potential to
      complement the traditional assays for serodiagnosis of RVF. Advantages of the N
      protein are its safety, stability and cost-effectiveness in use and production.

PMID- 17187945
TI  - Efficacy of enrofloxacin, florfenicol and amoxicillin against Ornithobacterium
      rhinotracheale and Escherichia coli O2:K1 dual infection in turkeys following APV
      priming.
AB  - Experimental groups of 15 susceptible 3-week-old turkeys were inoculated
      oculonasally with avian metapneumovirus (APV) subtype A and susceptible
      Escherichia coli O2:K1 and Ornithobacterium rhinotracheale (ORT) bacteria, with a
      3 days interval between viral and bacterial inoculation and approximately 8h
      between the two bacterial inoculations. The aims of the present study were to
      assess the efficacy of drinking-water administration of enrofloxacin for 3 and 5
      days, amoxicillin for 5 days and florfenicol for 5 days for the treatment of the
      resulting respiratory disease, based on clinical and bacteriological
      examinations. Antimicrobial treatment started 1 day after dual bacterial
      inoculation. After infection, the birds were examined and scored for clinical
      signs daily, weighed at different times, and their tracheae swabbed daily. Five
      birds were euthanised and examined for macroscopic lesions at necropsy at 5 days
      post-bacterial inoculation (dpbi) and the remainder at 15dpbi. Samples of the
      turbinates, trachea, lungs, sinuses, air sacs, heart, pericardium and liver were
      collected for bacteriological examination. Recovery from respiratory disease
      caused by an APV/E. coli/ORT triple infection in 3-week-old turkey poults was
      overall most successful after enrofloxacin treatment, irrespective of treatment
      duration, followed by florfenicol treatment. Compared with the untreated group,
      clinical signs as well as ORT and E. coli multiplication in the respiratory tract
      were significantly reduced by both enrofloxacin treatments and the florfenicol
      treatment, with the enrofloxacin treatments showing significantly better
      reductions than the florfenicol treatment. Five-day treatment with amoxicillin,
      compared with the untreated group, did not cause a significant reduction in any
      of the aforementioned parameters.

PMID- 17187947
TI  - Study of thermal behaviour of sugar esters.
AB  - Sugar esters (SEs) are widely used in the pharmaceutical and food industries.
      They have a wide range of HLB values (1-16), and hence they can be applied as
      surfactants, or as solubility or penetration enhancers. SEs can be employed in
      hot-melt technology, because their melting points are low and they decompose only
      above 220 degrees C. The aims of this work were to study the thermal properties
      of SEs and to demonstrate differences between SEs with various HLB values. The
      results revealed that SEs with high or medium HLB values were vitrified by
      melting. Their glass transitions (T(g)) were determined by modulated differential
      scanning calorimetry. To visualize the changes in the samples during heating, hot
      stage microscopy was used. Hydrophilic SEs were only softened, while lipophilic
      SEs were melted by heating. After melting and solidification, SEs have partially
      amorphous layered structures which slowly crystallize in time. Time-dependent
      solid-state changes (crystalline and amorphous phases) were observed, and
      analysed by means of differential scanning calorimetry and X-ray powder
      diffraction.

PMID- 17187946
TI  - Genetic polymorphisms, hormone levels, and hot flashes in midlife women.
AB  - OBJECTIVE: Hot flashes disrupt the lives of millions of women each year. Although
      hot flashes are a public health concern, little is known about risk factors that
      predispose women to hot flashes. Thus, the objective of this study was to examine
      whether sex steroid hormone levels and genetic polymorphisms in hormone
      biosynthesis and degradation enzymes are associated with the risk of hot flashes.
      METHODS: In a cross-sectional study design, midlife women aged 45-54 years
      (n=639) were recruited from Baltimore and its surrounding counties. Participants
      completed a questionnaire and donated a blood sample for steroid hormone analysis
      and genotyping. The associations between genetic polymorphisms and hormone
      levels, as well as the associations between genetic polymorphisms, hormone
      levels, and hot flashes were examined using statistical models. RESULTS: A
      polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate
      (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was
      associated with higher testosterone and DHEA-S levels. Lower progesterone and sex
      hormone binding globulin levels, lower free estradiol index, and a higher ratio
      of total androgens to total estrogens were associated with the experiencing of
      hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3betaHSD were both
      associated with hot flashes. CONCLUSION: Some genetic polymorphisms may be
      associated with altered levels of hormones in midlife women. Further, selected
      genetic polymorphisms and altered hormone levels may be associated with the risk
      of hot flashes in midlife women.

PMID- 17187948
TI  - Intrapericardial administration of novel DNA formulations based on
      thermosensitive Poloxamer 407 gel.
AB  - Inherited cardiopathies are leading to life-threatening conditions such as heart
      failure. Moreover, treatments currently available fail in altering the cardiac
      phenotype. Thus, gene therapy appears as an attracting alternative to
      conventional treatments. However, gene delivery remains a major hurdle in
      achieving this goal. To obtain regional delivery of plasmid DNA, intrapericardial
      administration seems to be an interesting approach. In order to improve retention
      time at the site of injection, formulations based on a thermosensitive gel of
      Poloxamer 407 were assessed. Protection and condensation of plasmid DNA was
      initially performed through complexation with polyethyleneimine (PEI), a widely
      used polymer. Characterization of the size and zeta potential of the complexes
      suggested interactions between the polyplexes and the Poloxamer gel through
      significant increase of the size of the polyplexes and shielding of the surface
      charges. In vivo evaluation has highlighted the toxicity of PEI/DNA polyplexes
      toward the myocardium. However, feasibility of intrapericardial injection of
      Poloxamer based formulations as well as their very low toxicity has been
      established.

PMID- 17187950
TI  - Knowledge and use of medicinal plants by people around Debre Libanos monastery in
      Ethiopia.
AB  - The study was conducted around Debre Libanos monastery from October 2005 to June
      2006. A total of 250 villagers, 13 monks and 3 nuns were interviewed using
      semistructured questionnaire on the knowledge and use of medicinal plants. The
      informant consensus factor (ICF) and the fidelity level (FL) of the species were
      determined. Eighty medicinal plant species were reported. The average medicinal
      plant reported by a female is 1.67+/-0.33 and a male is 5.77+/-0.71 with
      significant difference between them (alpha=0.05, p=0.023). The ICF values
      demonstrated that local people tend to agree more with each other in terms of the
      plants used to treat 'Mich' and headache (0.69) and intestinal illness and
      parasites (0.68) but a much more diverse group of plants are cited to treat
      problems related to rabies (0.14) and unidentified swelling and cancer (0.11).
      The FL values are also similar to ICF values. The knowledge of the villagers
      close to the monastery is found to be higher than those distant from the
      monastery and the correlation between Abichu and Telaye (r=0.970, alpha=0.05,
      p=0.001), and Zegamel and Doreni (r=0.745, alpha=0.05, p=0.027) is significant
      indicating the relationships between the number of plants reported by the
      informants and the distance from the monasteries to the villages. This study was
      not able to determine the knowledge difference between the villagers and the
      monastery dwellers because the monks and nuns were not willing to give
      information on the knowledge and use of medicinal plants. This may result in the
      long run in loss of local knowledge in the surrounding area and the country at
      large for preparation of pharmacologically effective remedies.

PMID- 17187949
TI  - Fusogenic peptides enhance endosomal escape improving siRNA-induced silencing of
      oncogenes.
AB  - Small interfering RNA (siRNA) molecules are the functional mediators of a post
      transcriptional gene silencing process known as RNA interference (RNAi). The
      silencing of genes involved in diseases, using siRNA, is considered a very
      promising therapeutic strategy. However, as for all the nucleic acid based
      therapeutics, these negatively charged and hydrophilic molecules do not readily
      cross biological membranes. The use of cationic carriers generally results in
      positively charged complexes which are taken up by cells through endocytosis.
      Still, for gene silencing, these complexes need to escape through the endosomal
      membrane, thereby reaching the cytosol where all the RNAi machinery is present.
      One of the strategies developed to facilitate endosomal escape mimics the fusion
      of viral envelopes with host cell endosomal membranes, which occurs during viral
      infections. Several synthetic fusogenic peptides have been synthesized based on
      the fusion domain of the influenza virus. In this study we evaluated the effects
      of the influenza-derived fusogenic peptide diINF-7 on gene silencing efficiency
      of siRNA targeting the epidermal growth factor receptor (EGFR) and the K-ras
      oncogenes. For both targets, strong enhancement of gene silencing activity was
      noted after addition of diINF-7 fusogenic peptide, identifying endosomal escape
      as a limiting factor for siRNA silencing efficiency.

PMID- 17187951
TI  - The corner of the coloproctologist: what to ask to radiologist.
AB  - Defecation disorders, fecal incontinence, often associated to urinary and genital
      dysfunction, represent symptoms of a large number of functional and structural
      alterations of pelvic floor. They can be evaluated by functional and morphologic
      tests. A perfect anatomic and functional knowledge of the anorectum and pelvic
      floor is indispensable for a correct diagnostic and therapeutic path.
      Incontinence due to sphincter lesions can be diagnosed only by imaging
      techniques. In defecation disorders the issue is complex because functional and
      anatomic alterations can coexist. The radiological diagnosis of dyssynergic
      defecation is a diagnosis of confidence that enhances its value when manometric
      and electromyographic evidence of pelvic dyssynergia are detected. When
      anatomical alterations are detected the aim is to understand their
      physiopathology, to make a more precise diagnosis and treatment, and to minimize
      the errors of an inappropriate therapy. Our attention is focused on the
      information provided by imaging techniques about anorectum and pelvic floor
      abnormalities for optimal therapeutic planning.

PMID- 17187952
TI  - Sixty-four-MSCT in the characterization of porcine acute and subacute myocardial
      infarction: determination of transmurality in comparison to magnetic resonance
      imaging and histopathology.
AB  - OBJECTIVE: The aim of this study was to assess the accuracy of MSCT in
      characterizing myocardial infarction (MI) and, thereby, determine the extent of
      early perfusion defect (ED), microvascular obstruction (MO) and transmural depth
      of late enhancement (LE) in comparison to MRI and histology. MATERIALS AND
      METHODS: Seven pigs were studied with MSCT (Somatom Sensation 64) and MRI
      (Magnetom Sonata) a median 1 and 21 days following temporary occlusion of a
      diagonal branch and creation of small reperfused infarction. For depiction of ED,
      CT images were acquired in the early arterial phase and following 35 s; LE and MO
      were evaluated on images obtained at 3, 5, 10 and 15 min. Thereby, a bolus/low
      flow contrast injection protocol was used. Triphenyltetrazolium-chloride (TTC)
      stain and histology were obtained. Volumes of enhancement patterns were assessed
      as percentage of the ventricle and compared by Bland-Altman analysis. Segmental
      co-localization and graded transmurality was evaluated with weighted-kappa-test.
      RESULTS: Close spatial agreement was observed for MRI-MO and MSCT-MO (bias=0.55;
      CI=-1.49 to 2.60 at 5 min MSCT), TTC and MSCT-LE (bias=-1.28; CI=-3.76 to 1.19)
      or MRI-LE and MSCT-LE (bias=-0.79; CI=-4.19 to 2.60). There was good segmental co
      localization for MO (weighted kappa=0.93) and high agreement for transmural
      extent of TTC, MRI-LE and MSCT-LE (weighted kappa=0.84 TTC versus MSCT; 0.86 MRI
      versus MSCT). Arterial and 35s ED significantly underestimated infarct size and
      showed poor segmental or transmural agreement (weighted kappa=0.33; 0.44).
      CONCLUSIONS: MSCT late-scans not only reliably depict size of MO and LE in acute
      or subacute infarct phases but, moreover, allow for accurate determination of LE
      transmurality.

PMID- 17187953
TI  - Selection of background electrolyte for CZE analysis by a chemometric approach.
      Part I. Separation of a mixture of acidic non-steroidal anti-inflammatory drugs.
AB  - This paper is the first part of the presentation of a chemometric approach for
      the rapid selection of a suitable background electrolyte (BGE) in CZE analysis of
      small drug molecules. The strategy is based on principal component analysis and
      experimental design. In this first section, the approach is applied to the
      analysis of a mixture of six arylpropionic anti-inflammatory drugs. Initially,
      222 possible aqueous background electrolytes (objects) were characterized using
      as descriptors pH, conductivity, ionic strength and relative viscosity. In order
      to allow the dissociation of the acidic analytes, this original data set was
      reduced to 154 background electrolytes with pH values higher than or equal to 5.
      Principal component analysis made it possible to graphically represent the new
      set of objects, described by the four variables, in a two-dimensional space.
      Among these electrolytes, Kennard-Stone algorithm selected ten objects to be
      tested by CZE, covering homogeneously principal component space. CZE analyses
      were carried out with the selected electrolytes, and 0.1 M borax was identified
      as the most suitable one for the specified application. Finally, the
      characteristics of the analysis were finely tuned by means of a response surface
      study, which allowed the best conditions to be determined: borax concentration,
      0.09 M; methanol, 6% (v/v); temperature, 24 degrees C, voltage, 20 kV. Applying
      these conditions, a baseline resolution among the six compounds was obtained in
      less than 10 min.

PMID- 17187954
TI  - Selection of background electrolyte for CZE analysis by a chemometric approach.
      Part II. Separation of a mixture of basic beta-blocker drugs.
AB  - In the first part of this study a chemometric approach to choose a suitable
      background electrolyte for CZE analysis was introduced. Two hundred and twenty
      two possible electrolytes were previously characterized by means of the
      descriptors pH, conductivity, ionic strength and relative viscosity and the
      approach was applied to the separation of a mixture of acidic drugs. In this
      second part, another application concerning the analysis of basic drugs is
      presented. The test mixture was made of eight beta-blocker drugs. According to
      the basic nature of the analytes, the original data set was reduced to a new
      subset of 117 objects with pH less than or equal to 7, and after computing
      principal components the new set of objects was represented in a two-dimensional
      space. Ten objects to be tested in CZE, capable of covering homogeneously the
      principal component space, were selected by means of Kennard-Stone algorithm. The
      data set was further reduced around the BGEs which gave the best results, and a
      new set of electrolytes to be tested was selected. Using pH 4 citrate buffer, an
      electropherogram with baseline resolution was obtained in 10 min. A Doehlert
      design was run to further reduce analysis time, and applying the optimized
      conditions (voltage, 23 kV; temperature, 26 degrees C) the separation was
      obtained in about 7 min.

PMID- 17187955
TI  - Caution to HPLC analysis of tricarbonyl technetium radiopharmaceuticals: an
      example of changing constitution of complexes in column.
AB  - Radio-HPLC is a powerful tool for analyzing radioactive species in
      radiopharmaceutical chemistry. In this paper, we found an example that the
      commonly used eluting solvent, acetonitrile, could coordinate with the popular
      radiopharmaceutical nuclides, technetium-99m, during chromatography.
      [(99m)Tc(CO)(3)(H(2)O)(3)](+) and [Re(CO)(3)(H(2)O)(3)](+) showed quite different
      retention time when they were eluted using acetonitrile/water as mobile phase.
      However, they almost demonstrated the same retention time when they were eluted
      using methanol/water as mobile phase. Further analysis showed that both
      [(99m)Tc(CO)(3)(H(2)O)(3)](+) and [Re(CO)(3)(H(2)O)(3)](+) could be changed into
      [(99m)Tc(CO)(3)(CH(3)CN)(3)](+) and [Re(CO)(3)(CH(3)CN)(x)(H(2)O)(3-x)](+) during
      the separation, respectively. Some former works mistook the
      [(99m)Tc(CO)(3)(CH(3)CN)(3)](+) for [(99m)Tc(CO)(3)(H(2)O)(3)](+) when using
      acetonitrile and water in analysis. Quality control of the radiopharmaceuticals
      containing metal complex should be careful since HPLC solvent could replace some
      liable ligand molecules.

PMID- 17187956
TI  - Antidiabetic activity of lipophilic (-)-epigallocatechin-3-gallate derivative
      under its role of alpha-glucosidase inhibition.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), a component of catechins, has been shown
      to reduce blood glucose levels. In the present study, we investigated the
      antidiabetic activity and its mechanism of lipophilic EGCG derivative (L-EGCGd)
      in streptozotocin (STZ)-induced diabetic rats. L-EGCGd was chemically modified
      from traditional hydrophilic EGCG. After 30 days treatment, plasma levels of
      glucose were significantly reduced by 40.5+/-7.0% and 17.0+/-2.8% in groups
      administered 50 or 25 mg kg(-1)d(-1) L-EGCGd, respectively, as compared with that
      in the diabetic control group. Lipid metabolites, such as total cholesterol (TC),
      triglyceride (TG) and low-density lipoprotein cholesterol (LDLC) were effectively
      attenuated by L-EGCGd administration, but plasma HDLC levels did not change
      significantly. The oral glucose tolerance test (OGTT) greatly revealed the
      improved ability of glucose tolerance with treatment of L-EGCGd. L-EGCGd only
      retarded the postprandial rise in blood glucose with sucrose loading but not
      glucose loading. And activity of alpha-glucosidase was inhibited by 50% at the
      concentration of 246.6 microg ml(-1) L-EGCGd. As a result, we first demonstrated
      that the purified form of compound L-EGCGd possessed the hypoglycemic effect
      under its role of alpha-glucosidase inhibition, and therefore should be possibly
      accepted as an alternative oral medication protecting patients against
      postprandial hyperglycemic toxicity on the treatment of diabetes and its
      complications.

PMID- 17187957
TI  - In vitro cytotoxicity mechanisms 46th ETCS International Meeting - Third
      International Joint Meeting AICC-CELLTOX.

PMID- 17187958
TI  - Cytochrome P450 destruction by benzene metabolites 1,4-benzoquinone and 1,4
      hydroquinone and the formation of hydroxyl radicals in minipig liver microsomes.
AB  - Reactive metabolites of benzene 1,4-benzoquinone and 1,4-hydroquinone exert their
      toxic effects through covalent and/or oxidative damage to DNA and proteins. Since
      minipigs have been proposed as a suitable model species in toxicological and
      pharmacological research, the aim of this study was to explore mechanisms by
      which catechol, 1,4-hydroquinone and 1,4-benzoquinone destroy cytochrome P450
      (P450) and induce oxidative stress in minipig liver microsomes. Our second goal
      was to assess the usefulness of minipig liver microsomes as a model system for
      the testing of the production of oxidative stress by clinically relevant quinone
      containing compounds, e.g. anthracyclines. Of the three benzene metabolites
      tested, the highest P450 destruction was caused by 1,4-benzoquinone. This
      destructive effect did not correlate with the production of hydroxyl radicals as
      measured by ESR spin trapping which was the highest in samples containing 1,4
      hydroquinone. Our results confirm previous findings that 1,4-benzoquinone exerts
      its effect mainly by direct attack on macromolecules while 1,4-hydroquinone
      rather stimulates the production of reactive oxygen species. Doxorubicin
      stimulated the production of hydroxyl radicals and the destruction of P450
      similarly as 1,4-hydroquinone. Minipig liver microsomes should be further tested
      as a possibly suitable model system for the testing of potential modulators of
      the toxicity of doxorubicin.

PMID- 17187960
TI  - A rapid one-tube PCR method for simultaneously differentiating homozygotes and
      heterozygotes of the Sp1 binding site polymorphism in collagen type Ialpha1.
AB  - Rapid detection of single-base changes is fundamental to molecular medicine. PCR
      amplification of specific alleles (PASA) has previously been used as a rapid
      method of genotyping single-nucleotide changes, but one reaction is required for
      each allele. This paper describes a Bidirectional PASA (Bi-PASA) method, which
      was developed to distinguish between homozygotes and heterozygotes in one PCR
      reaction. The method is tested using the Sp1 polymorphism in Collagen type
      Ialpha1. The results demonstrate that Bi-PASA is a simple and rapid method for
      detecting the zygosity of the polymorphism in a single PCR reaction.

PMID- 17187959
TI  - Immune cell involvement in dorsal root ganglia and spinal cord after chronic
      constriction or transection of the rat sciatic nerve.
AB  - Chronic constriction injury (CCI) of the sciatic nerve in rodents produces
      mechanical and thermal hyperalgesia and is a common model of neuropathic pain.
      Here we compare the inflammatory responses in L4/5 dorsal root ganglia (DRGs) and
      spinal segments after CCI with those after transection and ligation at the same
      site. Expression of ATF3 after one week implied that 75% of sensory and 100% of
      motor neurones had been axotomized after CCI. Macrophage invasion of DRGs and
      microglial and astrocytic activation in the spinal cord were qualitatively
      similar but quantitatively distinct between the lesions. The macrophage and glial
      reactions around neurone somata in DRGs and ventral horn were slightly greater
      after transection than CCI while, in the dorsal horn, microglial activation
      (using markers OX-42(for CD11b) and ED1(for CD68)) was greater after CCI. In
      DRGs, macrophages positive for OX-42(CD11b), CD4, MHC II and ED1(CD68) more
      frequently formed perineuronal rings beneath the glial sheath of ATF3+ medium to
      large neurone somata after CCI. There were more invading MHC II+ macrophages
      lacking OX-42(CD11b)/CD4/ED1(CD68) after transection. MHC I was expressed in DRGs
      and in spinal sciatic territories to a similar extent after both lesions. CD8+ T
      lymphocytes aggregated to a greater extent both in DRGs and the dorsal horn after
      CCI, but in the ventral horn after transection. This occurred mainly by
      migration, additional T-cells being recruited only after CCI. Some of these were
      probably CD4+. It appears that inflammation of the peripheral nerve trunk after
      CCI triggers an adaptive immune response not seen after axotomy.

PMID- 17187961
TI  - Component-based visual clustering using the self-organizing map.
AB  - In this paper we present a new method for visual clustering of multi-component
      images such as trademarks, using the topological properties of the self
      organizing map, and show how it can be used for similarity retrieval from a
      database. The method involves two stages: firstly, the construction of a 2D map
      based on features extracted from image components, and secondly the derivation of
      a Component Similarity Vector from a query image, which is used in turn to derive
      a 2D map of retrieved images. The retrieval effectiveness of this novel component
      based shape matching approach has been evaluated on a set of over 10 000
      trademark images, using a spatially-based precision-recall measure. Our results
      suggest that our component-based matching technique performs markedly better than
      matching using whole-image clustering, and is relatively insensitive to changes
      in input parameters such as network size.

PMID- 17187962
TI  - Pituitary volume in neuroleptic-naive schizophrenia: a structural MRI study.
AB  - Abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) have been
      implicated in psychosis. To our knowledge, no prior study has measured pituitary
      volume in a neuroleptic-naive schizophrenic population. Herein, we present data
      exploring the volumetric differences in a sample of antipsychotic-naive patients
      with a DSM-IV diagnosis of schizophrenia versus appropriately matched healthy
      controls. Pituitary volumes were measured in 51 patients with schizophrenia (36
      males, 15 females, mean age+/-S.D.: 25.2+/-7.4 years) and 55 healthy controls (30
      males, 25 females; mean age+/-S.D.: 25.2+/-6.6 years) Measurements were conducted
      on 1.5 mm thick T1-weighted coronal images from a 1.5T scanner by two trained
      raters. Patients with schizophrenia had significantly smaller pituitary volumes
      than healthy control subjects (mean volume+/-S.D.=0.58+/-0.14 cm(3) and 0.66+/
      0.17 cm(3) respectively; ANCOVA (using intracranial volume, gender and age as
      covariates), F=6.81, df=1, 101; p=0.01). These findings provide new evidence of a
      smaller pituitary volume in neuroleptic-naive patients with schizophrenia. The
      observed alterations in pituitary volume are consistent with neuroendocrine
      studies that have reported abnormalities in the HPA axis in psychosis. Similar
      volume reductions have been seen in other neuropsychiatric populations and may
      cut across diagnostic boundaries.

PMID- 17187963
TI  - Adolescent adjustment disorder: precipitant stressors and distress symptoms of 89
      outpatients.
AB  - OBJECTIVE: Research on adolescent adjustment disorder (AD) is scarce. We
      characterized adolescent outpatients with AD in psychosocial background and
      treatment received compared with patients with other non-psychotic disorders
      (OND). Furthermore, we explored precipitant stressors, distress symptoms and
      behavioral problems among males and females with AD. METHOD: Data were collected
      prospectively on 290 consecutive psychiatric outpatients, aged 12-22 yrs, at a
      secondary care clinic in Finland. DSM-III-R diagnoses were assigned, based on all
      available information, at the end of treatment. RESULTS: AD was the second most
      common diagnosis among non-psychotic patients (31% of 290). Compared to OND
      patients, those with AD were predominantly female and had less severe
      psychosocial impairment. In multivariate comparisons school-related stressors,
      problems with law and restlessness characterized males, and parental illness and
      internalizing symptoms females with AD. Intensity and duration of treatment of AD
      patients varied widely. CONCLUSIONS: Adjustment disorder comprised a common
      clinical entity among adolescent outpatients. Psychiatric assessment and
      treatment should be individually targeted by taking into account gender-specific
      stressors and distress symptoms among young people with AD.

PMID- 17187964
TI  - ABCG1 gene variants in suicidal behavior and aggression-related traits.
AB  - The ABCG1 transporter seems to be involved in human cholesterol and sterol
      homeostasis. As alterations in cholesterol homeostasis have been widely linked to
      aggression, violence and suicidal behavior, we considered ABCG1 as a candidate
      gene for these traits. We studied 5 gene variants of ABCG1 in a sample of 571
      suicide attempters, healthy controls and suicide completers. We also analyzed the
      relation to aggression-related traits, assessed by STAXI and FAF. Regarding the
      genotypes, there was no association with completed or attempted suicide with the
      tested SNPs. Regarding alleles, only one SNP (rs1044317) showed a slight
      association with suicide attempters in comparison to the controls. Interestingly,
      rs225374 G allele carriers had higher scores on the STAXI subscales "State Anger"
      and "Anger Out", as well as on the FAF subscales "Spontaneous Aggression",
      "Irritability" and "Aggression". Carriers of the rs914189 G allele scored higher
      on the FAF subscales "Spontaneous Aggression", "Reactive Aggression" and
      "Aggression". Carriers of the rs1044317 G allele had lower scores for STAXI
      "Trait Anger" and "Trait Temperament", and higher scores for STAXI "Anger
      Control". Our results provide evidence that the ABCG1 may influence aggression
      related traits. Given that these represent intermediate phenotypes of suicidal
      behavior, ABCG1 might also act on suicidal behavior through these traits. The
      observed associations warrant further replications.

PMID- 17187965
TI  - Low-resolution brain electromagnetic tomography (LORETA) identifies brain regions
      linked to psychometric performance under modafinil in narcolepsy.
AB  - Low-resolution brain electromagnetic tomography (LORETA) showed a functional
      deterioration of the fronto-temporo-parietal network of the right hemispheric
      vigilance system in narcolepsy and a therapeutic effect of modafinil. The aim of
      this study was to determine the effects of modafinil on cognitive and
      thymopsychic variables in patients with narcolepsy and investigate whether
      neurophysiological vigilance changes correlate with cognitive and subjective
      vigilance alterations at the behavioral level. In a double-blind, placebo
      controlled crossover design, EEG-LORETA and psychometric data were obtained
      during midmorning hours in 15 narcoleptics before and after 3 weeks of placebo or
      400 mg modafinil. Cognitive investigations included the Pauli Test and complex
      reaction time. Thymopsychic/psychophysiological evaluation comprised drive, mood,
      affectivity, wakefulness, depression, anxiety, the Symptom Checklist 90 and
      critical flicker frequency. The Multiple Sleep Latency Test (MSLT) and the
      Epworth Sleepiness Scale (ESS) were performed too. Cognitive performance (Pauli
      Test) was significantly better after modafinil than after placebo. Concerning
      reaction time and thymopsychic variables, no significant differences were
      observed. Correlation analyses revealed that a decrease in prefrontal delta,
      theta and alpha-1 power correlated with an improvement in cognitive performance.
      Moreover, drowsiness was positively correlated with theta power in parietal and
      medial prefrontal regions and beta-1 and beta-2 power in occipital regions. A
      less significant correlation was observed between midmorning EEG LORETA and the
      MSLT; between EEG LORETA and the ESS, the correlation was even weaker. In
      conclusion, modafinil did not influence thymopsychic variables in narcolepsy, but
      it significantly improved cognitive performance, which may be related to medial
      prefrontal activity processes identified by LORETA.

PMID- 17187966
TI  - Chemical force titrations of antigen- and antibody-modified
      poly(methylmethacrylate).
AB  - Poly(methylmethacrylate) (PMMA) is a versatile polymer that displays desirable
      properties for development of cheap and disposable microfluidic devices for
      sensing biomolecular interactions. Atomic force microscopy (AFM) and chemical
      force titrations were used to determine the efficacy of surface modifications
      made to accommodate protein-substrate linkage. AFM images show the effects on
      surface morphology of carboxylated-, amine-, hCG antigen- and anti-hCG antibody
      modified PMMA substrates. Confocal microscopy was used to determine the
      fluorescent intensity of labeled antibody species on the PMMA substrate,
      confirming the success of surface antigen/antibody immobilization. Surface
      pK(1/2) value for carboxylic acid and amine species grafted on PMMA were
      determined. When carboxylic acid or amine-terminated tips were titrated against
      PMMA samples terminated with the hCG antigen and anti-hCG antibody, peaks
      appeared in the force titration curve consistent with the pI range of the antigen
      or antibody species. Strong adhesive forces were present at pH values above 7.0
      when the antigen was present on the PMMA substrate, and these were attributed to
      hydrophobic interactions between the antigen and the alkane "linker" chain
      attaching the amine or carboxylate group to the AFM tip. Such hydrophobic
      interactions were not observed with the carboxylic acid or amine/antibody
      combinations suggesting that the surface-linked antibody was more resistant to
      denaturation under higher pH. The results demonstrated the feasibility of using
      AFM approaches for interrogating protein grafting strategies in the fabrication
      of PMMA-based microsystems.

PMID- 17187967
TI  - Pharmacokinetic simulation of biowaiver criteria: the effects of gastric
      emptying, dissolution, absorption and elimination rates.
AB  - In vitro dissolution tests can be used to waive in vivo bioequivalency studies
      (biowaiver), if drug has high solubility and high permeability according to
      biopharmaceutics classification system (BCS I). Then absorption of BCS I drugs is
      not dependent on drug dissolution or gastrointestinal transit time and the solid
      dosage form behaves like oral solution. Currently biowaivers are determined based
      on solubility, permeability and dissolution, but the factors related to the
      gastrointestinal tract and the dynamic nature of drug dissolution and systemic
      pharmacokinetics are not taken into account. We utilized pharmacokinetic
      simulation model to study effects of formulation types, and different rates of
      dissolution and gastric emptying on drug concentrations in plasma. Simulated
      maximum concentration in plasma (C(max)) and area under the curve (AUC) values of
      solid dosage forms were compared to the simulations of oral solution. Based on
      simulations about half of BCS I drugs have higher risk to fail in bioequivalency
      (BE) study than BCS III drugs. For these BCS I compounds 10-25% differences of
      C(max) were observed. Rest of the BCS I drugs and all BCS III drugs have lower
      risk to fail in BE study since less than 10% difference in C(max) and AUC were
      observed. Pharmacokinetic simulation model was valuable tool to evaluate
      biowaiver criteria and to study the effects of drug and physiology
      gastrointestinal related factors on C(max) and AUC.

PMID- 17187968
TI  - Increased magnesium intake prevents hyperlipidemia and insulin resistance and
      reduces lipid peroxidation in fructose-fed rats.
AB  - Studies have suggested that type 2 diabetes mellitus is associated with abnormal
      lipid metabolism, oxidative stress and insulin resistance. Increased magnesium
      intake may improve dyslipidemia, oxidative stress and insulin insensitivity in
      type 2 diabetes. Therefore, the present study investigated the influence of
      increasing dietary magnesium from 0.1% to 1.0% for 4 weeks on plasma lipids,
      lipid peroxidation, l-ascorbic acid and insulin sensitivity in male Wistar rats
      fed a high-fructose diet. The rats were divided into control (CR), fructose-fed
      (FRU-fed) and fructose-fed supplemented with magnesium (FRU-Mg-fed) groups (n=8
      per group). Homeostasis model assessment for insulin resistance (HOMA-IR) and
      plasma thiobarbituric acid-reactive substances (TBARS) were used as indices of
      insulin sensitivity and lipid peroxidation, respectively. When compared with
      controls, the FRU-fed group had significantly higher values of HOMA-IR, fasting
      plasma glucose, insulin, triglyceride, total cholesterol/HDL-cholesterol ratio
      (atherogenic index), and TBARS. Their values in FRU-Mg-fed group were close to
      those of the controls. FRU-Mg-fed group had also significantly higher plasma
      magnesium and l-ascorbic acid levels, but significantly lower LDL-cholesterol
      levels than those in control and Fru-fed groups. CONCLUSION: increased magnesium
      intake improved insulin sensitivity, hyperglycemia, hyperlipidemia and reduced
      lipid peroxidation in fructose-fed rats.

PMID- 17187970
TI  - [Acquired non hypertrophic pyloric stenosis in children].
AB  - Pediatric non hypertrophic pyloric stenosis (NHPS) are uncommon. Their causes and
      treatments are debated. MATERIAL AND METHOD: Retrospective review of all cases of
      NHPS from 3 pediatric surgery services during the period 1984-2002. RESULTS: Six
      children, aged 17 months to 15 years, underwent surgery for NHPS. Clinical
      symptoms, food vomiting and loss of weight, were present for several weeks before
      the diagnosis of NHPS was made. The diagnosis was peptic stenosis in 3 cases and
      has not been established in 3 cases. Search for Helicobacter pylori was negative
      in all cases. Failure of specific medical treatment and endoscopic dilatations
      led to pyloric resection in 3 cases and pyloroplasty in 3 cases. Post operative
      course was uneventful with normal oral feeding and normalisation of weight
      status. Histologic data were aspecific. No recurrence was observed. DISCUSSION:
      We discuss the origin of the pyloric stenosis, regarding clinical, operative and
      pathological data: were the stenosis the cause or consequence of peptic ulcer?
      Peptic disease is always advocated, but difficult to prove and may be excessively
      incriminated. Late symptomatic congenital and acquired idiopathic pyloric
      stenosis should be recalled. In all cases of proved pyloric stenosis, after
      failure of medical and endoscopic treatment, a simple surgical procedure
      (pyloroplasty) associated with medical treatment seems to be effective.
      CONCLUSION: The diagnosis of NHPS should be suspected in a child with food
      vomiting and loss of weight if his age is not concordant with hypertrophic
      pyloric stenosis. Upper gastro-intestinal series and endoscopy are diagnostic.
      The precise cause of the stenosis is more difficult to asses. When the medical
      treatment fails, a pyloroplasty is usually curative.

PMID- 17187969
TI  - [Pneumococcal meningitis mortality in children. Prognostic factors in a series of
      73 cases].
AB  - OBJECTIVE: Despite advances in antibiotic therapy strategies and pediatric
      intensive care, prognosis of Streptococcus pneumoniae meningitis remains very
      poor. To determine the factors associated with hospital mortality of children
      with pneumococcal meningitis. METHODS: We conducted a retrospective study of 73
      cases of childhood pneumococcal meningitis admitted in 4 teaching hospitals in
      the center of Tunisia during a 8-year period (1995-2002). RESULTS: Hospital
      mortality was 13.7% (10 of 71 patients), and neurologic sequela were observed in
      34.5% of survivors. Based on univariable analysis, five variables were associated
      with the outcome: Pediatric Risk of Mortality score (p < 0.001), coma (p=0.0009),
      use of mechanical ventilation (p=0.0001), convulsions (p = 0.0449), and shock
      (p=0.0085). In multivariable analysis, only 2 factors were independently
      associated with in-hospital mortality: Pediatric Risk of Mortality score and the
      use of mechanical ventilation. 11.8% of pneumococcal isolates were intermediate
      and resistant to penicillin. Non-susceptible pneumococcus strains to penicillin
      and the use of steroids were not associated significantly with the mortality
      rate. CONCLUSIONS: Pneumococcal meningitis remains a devastating childhood
      disease. Two variables were independently associated with the in-hospital death
      in our series (high Pediatric Risk of Mortality score, and the use of mechanical
      ventilation). According to these data we may recommend the inclusion of
      vaccination against streptococcus pneumonia in the children's immunization
      program in Tunisia.

PMID- 17187971
TI  - Characterization of lactic acid bacteria isolated from the one humped camel milk
      produced in Morocco.
AB  - One hundred and twenty (120) strains of lactic acid bacteria (LAB) were
      enumerated and isolated from raw dromedary milk in Morocco using various cultured
      media. Strains isolated were characterized by phenotypic, physiological and
      biochemical properties. Results showed that high counts of LAB were found.
      Presumptive lactobacilli counts ranged from 2.5x10(2) to 6x10(7)cfu/ml,
      presumptive lactococci levels varied from 5x10(2) to 6x10(7)cfu/ml, presumptive
      streptococci counts varied from 4.2x10(2) to 8x10(7)cfu/ml, presumptive
      leuconostoc levels ranged from 5.4x10(2) to 5.4x10(7)cfu/ml. Results showed also
      that Lactobacillus and Lactococcus were the predominant genera with 37.5% and
      25.8%, respectively. The dominated species found were Lactococcus lactis subsp.
      lactis (17.5%), Lactobacillus helveticus (10%), Streptococcus salivarius subsp.
      thermophilus (9.20%), Lactobacillus casei subsp. casei (5.80%) and Lactobacillus
      plantarum (5%). This is the first report on the characterization of LAB strains
      isolated from the one humped camel milk produced in Morocco.

PMID- 17187972
TI  - Effect of Thymol on the spontaneous contractile activity of the smooth muscles.
AB  - Effects of Thymol on the spontaneous contractile activity (SCA) have been found
      in in vitro experiments with circular smooth-muscle strips (SMAs) from guinea pig
      stomach and vena portae. Thymol was found to possess an agonistic effect on the
      alpha(1)-, alpha(2)- and beta-adrenergic receptors. Its spasmolytic effect is
      registered at doses higher than 10(-6)M. Thymol in a dose of 10(-4)M inhibits
      100% the SCA of the SMAs and reduces the excitatory effect of 10(-5)M ACH to 35%.
      It is assumed that Thymol has an analgesic effect through its action on the
      alpha(2)-adrenergic receptors of the nerve cells. By influencing the beta
      adrenergic receptors in the adipose cells, it is possible to induce increased
      synthesis of fatty acids and glycerol, which is a prerequisite for increased heat
      release.

PMID- 17187973
TI  - Inhibition of phospholipase A2 reduces neurite outgrowth and neuronal viability.
AB  - Phospholipase A2 (PLA(2)) has been implicated in neurodevelopmental processes and
      in the early development of the nervous system. We investigated the effects of
      the inhibition of calcium-dependent and calcium-independent subtypes of cytosolic
      PLA2 (cPLA2 and iPLA2) on the development and viability of primary cultures of
      cortical and hippocampal neurons. PLA2 in these cultures was continuously
      inhibited with methylarachidonyl-fluorophosphonate (MAFP), an irreversible
      inhibitor of cPLA2 and iPLA2, or with bromoenol lactone (BEL), an irreversible
      selective iPLA2 inhibitor. The effect of PLA2 inhibitors on the development of
      neuronal cultures was ascertained by total cell count and morphological
      characterisation. Neuronal viability was quantified with MTT assays. Inhibition
      of PLA2 resulted in reduction of neuritogenesis and neuronal viability,
      disrupting neuronal homeostasis and leading to neuronal death. We conclude that
      the functional integrity of both calcium-dependent and calcium-independent
      cytosolic PLA2 is necessary for the in vitro development of cortical and
      hippocampal neurons.

PMID- 17187974
TI  - Effects of long-term treatment with montelukast in mild cystic fibrosis (long
      term treatment with montelukast in cystic fibrosis).

PMID- 17187975
TI  - Use of zeolitised coal fly ash for landfill leachate treatment: a pilot plant
      study.
AB  - Treatment of municipal solid waste (MSW) landfill leachate generally results in
      low percentages of nutrient removal due to the high concentration and
      accumulation of refractory compounds. For this reason, individual physical,
      chemical and biological processes have been used for the treatment of raw
      landfill leachate and sometimes for the mixture of domestic wastewater and
      landfill leachate. In this work, the possibility of treating landfill leachate
      was tested in a bench-scale pilot plant by a two-step method combining adsorption
      and coagulation-flocculation. Zeolite synthesized from coal fly ash, a by-product
      of coal-fired power stations, was used in this study both as a decantation aid
      reagent and as an adsorbent of COD and NH4-N. The coagulation-flocculation step
      was performed by the use of aluminium sulphate and a polyelectrolyte (ACTIPOL A
      401). The leachate was collected directly from a storage unit of the organic
      fraction of MSW, before it was composted. For this reason the raw leachate was
      diluted before treatment. The sludge was recirculated to enhance the removal
      efficiency of nutrients as well as to optimize flocculant saving and to decrease
      sludge production. The results showed that it is possible to remove 43%, 53% and
      82% of COD, NH4-N, and suspended solids, respectively. Therefore, this method may
      be an alternative for ammonium removal, as well as a suitable pre- or post
      treatment step, in combination with other processes in order to meet regulatory
      limits.

PMID- 17187976
TI  - Label-free detection of single nucleotide polymorphisms utilizing the
      differential transfer function of field-effect transistors.
AB  - We present a label-free method for the detection of DNA hybridization, which is
      monitored by non-metallized silicon field-effect transistors (FET) in a
      microarray approach. The described method enables a fast and fully electronic
      readout of ex situ binding assays. The label-free detection utilizing the field
      effect is based on the intrinsic charge of the DNA molecules and/or on changes of
      the solid-liquid interface impedance, when biomolecules bind to the sensor
      surface. With our sensor system, usually a time-resolved, dc readout is used. In
      general, this FET signal suffers from sensor drift, temperature drift, changes in
      electrolyte composition or pH value, influence of the reference electrode, etc.
      In this article, we present a differential ac readout concept for FET
      microarrays, which enables a stable operation of the sensor against many of these
      side-parameters, reliable readout and a possibility for a quick screening of
      large sensor arrays. We present the detection of point mutations in short DNA
      samples with this method in an ex situ binding assay.

PMID- 17187977
TI  - Detection of epidermal growth factor receptor (EGFR) mutations in non-small cell
      lung cancer (NSCLC) using a fully automated system with a nano-scale engineered
      biomagnetite.
AB  - A fully automated system using nano-scale engineered biomagnetite was developed
      to detect mutations in the epidermal growth factor receptor (EGFR) gene in non
      small cell lung cancer (NSCLC). Bacterial magnetic particles (BacMPs) were
      isolated from the magnetic bacterium Magnetospirillum magneticum AMB-1 and
      conjugated to streptavidin. Biotin-labeled target PCR products were then captured
      with the BacMPs, hybridized with the detection probe and detected by fluorescence
      signaling. The process was performed using a newly designed automated processor
      equipped with an XYZ mobile arm containing a 96-way automated pipetter, reagent
      dispenser and fluorescence detector. Two types of somatic mutations (in-frame
      deletions and point substitutions) in the EGFR gene were successfully identified
      within 3.5h using this system, suggesting that this system could be used in
      clinical tests of EGFR gene mutations in lung cancer, and potentially other
      cancer, patients. Additionally, a very low mutation rate could be detected in
      these samples.

PMID- 17187978
TI  - Flow sandwich-type immunoassay in microfluidic devices based on negative
      dielectrophoresis.
AB  - Microparticles have been manipulated in a microfluidic channel by means of
      negative dielectrophoresis (n-DEP), and the approach applied to a heterogeneous
      immunoassay system. A microfluidic device, with three-dimensional (3-D)
      microelectrodes fabricated on two substrates, was used to manipulate particle
      flow in the channel and to capture the particles in the caged area that was
      enclosed by the collector electrodes. Polystyrene microparticles (6 microm
      diameters) modified with anti-mouse immunoglobulin G (IgG) were manipulated and
      captured in the caged area when surrounded by intense n-DEP electric fields.
      Specifically, particles were trapped when AC voltages with amplitudes of 6-15
      V(peak) and frequencies over 500 kHz were applied to the two facing
      microelectrodes. A heterogeneous sandwich immunoassay was achieved by
      successively injecting a sample solution containing mouse antigen (IgG), and a
      solution containing a secondary antibody with a signal source (FITC-labeled anti
      mouse IgG antibody), into the channel. The fluorescence intensity from captured
      particles in the caged area increased with increasing concentrations (10 ng/ml to
      10 microg/ml) of mouse IgG. The described system enables mouse IgG to be assayed
      in 40 min. Thus, the automatic separation of free fractions from desired analytes
      and labeled antibodies can be achieved using a microfluidic device based on n
      DEP.

PMID- 17187979
TI  - Lymphedema following axillary lymph node dissection for breast cancer.
AB  - Lymphedema is a relatively common, potentially serious and unpleased complication
      after axillary lymph node dissection (ALND) for breast cancer. It may be
      associated with functional, esthetic, and psychological problems, thereby
      affecting the quality-of-life (QOL) of breast cancer survivors. Objective
      measurements (preferentially by measuring arm volumes or arm circumferences at
      predetermined sites) are required to identify lymphedema, but also subjective
      assessment can help to determine the clinical significance of any
      volume/circumference differences. Lymphedema per se predisposes to the
      development of other secondary complications, such as infections of the upper
      limb, psychological sequelae, development of malignant tumors, alterations of the
      QOL, etc. The risk of lymphedema is associated with the extent of ALND and the
      addition of axillary radiation therapy. Treatment involves the application of
      therapeutic measures of the so-called decongestive lymphatic therapy. Prevention
      is of key importance to avoid lymphedema formation. The application of the
      sentinel lymph node biopsy in the management of breast cancer has been associated
      with a reduced incidence of lymphedema formation.

PMID- 17187980
TI  - Novel 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin-like growth
      factor I (IGF-1R) kinase.
AB  - A novel class of 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin
      like growth factor I (IGF-1R) kinase is described. This report discusses the SAR
      of 4-(2-hydroxy-2-phenylethylamino)-substituted pyridones with improved IGF-1R
      potency.

PMID- 17187981
TI  - Reproduction and longevity: secrets revealed by C. elegans.
AB  - What is the relationship between reproduction and longevity? Evolutionary biology
      suggests that reproduction exacts a cost in somatic maintenance, a cost that
      reduces longevity. The frequent occurrence of this tradeoff between life span and
      fecundity, both due to experimental manipulations as well as natural variation,
      suggest that the mechanism might be conserved during evolution. Until recently,
      little was known about the mechanistic details of how reproduction might regulate
      life span. Here we discuss recent advances in our understanding of the regulation
      of life span by reproductive signaling, focusing on studies using Caenorhabditis
      elegans.

PMID- 17187982
TI  - Regulated translational bypass of stop codons in yeast.
AB  - Stop codons are used to signal the ribosome to terminate the decoding of an mRNA
      template. Recent studies on translation termination in the yeast Saccharomyces
      cerevisiae have not only enabled the identification of the key components of the
      termination machinery, but have also revealed several regulatory mechanisms that
      might enable the controlled synthesis of C-terminally extended polypeptides via
      stop-codon readthrough. These include both genetic and epigenetic mechanisms.
      Rather than being a translation 'error', stop-codon readthrough can have
      important effects on other cellular processes such as mRNA degradation and, in
      some cases, can confer a beneficial phenotype to the cell.

PMID- 17187984
TI  - Laws, guidelines and professional choice.

PMID- 17187983
TI  - Efficiency of fleece-bound sealing (TachoSil) of air leaks in lung surgery: a
      prospective randomised trial.
AB  - OBJECTIVE: Persistent air leakage following pulmonary resection is a major
      limiting factor for discharge from hospital. The aim of this study was to
      evaluate the sealing capacity of TachoSil for the closure of alveolar air leaks
      following parenchymal resections and to determine its effect on time to chest
      drain removal and duration of hospitalisation. METHODS: A total of 173 patients
      undergoing lobectomy or segmentectomy were enrolled in a single-centre,
      randomised study to compare the efficacy of TachoSil with standard treatment.
      Alveolar air leaks were evaluated intraoperatively by submersion of the resection
      site in saline and were graded according to the Macchiarini scale as 0 (no
      bubbles), 1 (single bubbles), 2 (stream of bubbles), 3 (coalescent bubbles).
      Patients with grade 1 or 2 air leaks were randomised to TachoSil or standard
      treatment. Grade 3 patients received standard treatment until the air leak was
      downgraded to grade 1 or 2 at which point they were randomised. Patients with
      grade 0 leakage were excluded. The primary efficacy endpoints of the study were
      postoperative quantification of air leakage on postoperative days 1 and 2. Other
      efficacy measurements included mean time to chest drain removal and mean time to
      hospital discharge. RESULTS: The mean intraoperative post-treatment air leakage
      was significantly lower in the TachoSil group (153.32ml/min, range: 10-450ml/min)
      compared with the standard treatment group (251.04ml/min, range: 15-970ml/min;
      P=0.009). The significant difference in air leakage volume observed
      intraoperatively post-treatment was maintained postoperatively. TachoSil showed a
      trend towards reduced incidence of postoperative leakage when measured >48h or >7
      days after surgery (30.7% vs 38.96% and 24% vs 32.46%, respectively). The mean
      times to chest drain removal and to hospital discharge were significantly reduced
      following the use of TachoSil (5.1 days vs 6.3 days, P=0.022 and 6.2 days vs 7.7
      days, P=0.01, respectively). CONCLUSIONS: The use of TachoSil following pulmonary
      resection resulted in a reduction in air leakage compared with standard
      techniques. This reduction in air leakage resulted in a significant reduction in
      both the time to chest drain removal and the period of hospitalisation.

PMID- 17187985
TI  - A new device for the identification of lymph nodes at lung cancer surgery.
AB  - In order to provide a precise lymph node mapping during lung cancer surgery a
      sterilizable plastic tray moulded in the shape of the mediastinum and lungs is
      presented by the author. The device makes lymph node mapping simpler, safer,
      quicker and methodically more structured. A positive impact is expected as a
      result of usage of the device from making pathologist's work easier and
      facilitating the flux of information on the surgeon-pathologist-oncologist
      pneumonologist chain to be more disinformation-free.

PMID- 17187986
TI  - Baicalin attenuates oxygen-glucose deprivation-induced injury via inhibiting NMDA
      receptor-mediated 5-lipoxygenase activation in rat cortical neurons.
AB  - The flavonoid baicalin exerts neuroprotective effects but the mechanism is not
      fully clarified. On the other hand, 5-lipoxygenase (5-LOX) activation is involved
      in ischemic neuronal injury. In this study, we determined whether baicalin
      protects rat cortical neurons against oxygen-glucose deprivation (OGD)-induced
      ischemic-like injury, if so, whether this effect relates to 5-LOX activation.
      After the neurons were injured by 1.5-h OGD and 24-h recovery, their viability
      reduced and necrosis occurred; these injuries were attenuated by baicalin (1 and
      5microM) as well as caffeic acid (a 5-LOX inhibitor, 5 and 25microM) and MK-801
      (an NMDA receptor antagonist, 1-10microM). OGD-induced 5-LOX translocation to the
      nuclear envelope as detected by immunoblotting, immunocytochemistry and 5-LOX
      transfection; this translocation was inhibited by baicalin (5microM) and MK-801
      (5microM) but not by caffeic acid (5microM). During 0.5- to 2-h recovery after
      1.5-h OGD, the production of 5-LOX metabolites, cysteinyl leukotrienes, was
      increased; this increased production was inhibited by baicalin and MK-801, while
      both the increased and baseline production were inhibited by caffeic acid. In
      addition baicalin and MK-801, not caffeic acid, inhibited glutamate-induced
      elevation of intracellular calcium. These results indicate that baicalin
      attenuates ischemic-like injury in the neurons, and this effect partly relates to
      the inhibition of NMDA receptor-mediated 5-LOX activation.

PMID- 17187987
TI  - Expression, purification and characterization of recombinant severe acute
      respiratory syndrome coronavirus non-structural protein 1.
AB  - The coronavirus (CoV) responsible for severe acute respiratory syndrome (SARS),
      SARS-CoV, encodes two large polyproteins (pp1a and pp1ab) that are processed by
      two viral proteases to yield mature non-structural proteins (nsps). Many of these
      nsps have essential roles in viral replication, but several have no assigned
      function and possess amino acid sequences that are unique to the CoV family. One
      such protein is SARS-CoV nsp1, which is processed from the N-terminus of both
      pp1a and pp1ab. The mature SARS-CoV protein is present in cells several hours
      post-infection and co-localizes to the viral replication complex, but its
      function in the viral life cycle remains unknown. Furthermore, nsp1 sequences are
      highly divergent across the CoV family, and it has been suggested that this is
      due to nsp1 possessing a function specific to viral interactions with its host
      cell or acting as a host specific virulence factor. In order to initiate
      structural and biophysical studies of SARS-CoV nsp1, a recombinant expression
      system and a purification protocol have been developed, yielding milligram
      quantities of highly purified SARS-CoV nsp1. The purified protein was
      characterized using circular dichroism, size exclusion chromatography, and multi
      angle light scattering.

PMID- 17187990
TI  - Crystallization of sparingly soluble stress-related proteins from cyanobacteria
      by controlled urea solublization.
AB  - The phycobilisome photosynthetic antenna complex, found in cyanobacteria and red
      algae, interacts with proteins expressed specifically to deal with different
      forms of physiological stress. Under conditions of nutrient starvation, the NblA
      protein is required for the process that leads to phycobilisome degradation and
      bleaching of the cells. HspA, a 16.5 kDa heat shock protein expressed in
      cyanobacterial cells, has been shown to provide functional stability to the
      phycobilisome during heat stress. We have cloned the genes encoding for these
      proteins into bacterial expression vectors in order to determine their three
      dimensional structures. The resulting recombinant proteins were found to be
      sparingly soluble, limiting their usefulness in the performance of
      crystallization experiments. We have developed a novel protocol that utilizes
      relatively high concentrations of urea to afford sufficient solubility to the
      protein. This has lead to the successful growth of diffraction quality crystals
      of these proteins. Complete data sets collected to 2-2.5A from crystals of both
      proteins shows that the crystals are stable, and useful for structure
      determination. A preliminary structure of the NblA shows that denaturation has
      not occurred and specific protein-protein interactions have been preserved. We
      believe that this protocol may be a generally advantageous method to obtain well
      diffracting crystals of sparingly soluble proteins.

PMID- 17187989
TI  - Bootstrap resampling for voxel-wise variance analysis of three-dimensional
      density maps derived by image analysis of two-dimensional crystals.
AB  - Difference density maps are commonly used in structural biology for identifying
      conformational changes in macromolecular complexes. For interpretation of the
      results, it is essential to estimate the variance or standard deviation of the
      difference density and the distribution of errors in space. In order to compare
      three-dimensional density maps of gap junction channels with and without the C
      terminal regulatory domain, we developed a bootstrap resampling method for
      estimation of the voxel-wise standard deviation. The bootstrap approach has been
      successfully used for estimating the sampling distribution from a limited data
      set and for estimating the statistical properties of the derived quantities
      [Efron, B., 1979. Bootstrap methods: another look at the jackknife. Ann. Stat. 7,
      1-26]. In our application, the standard deviation map can be estimated by
      bootstrapping the images. Our results show that, apart from the symmetry axes and
      small regions bordering the lumen of the extracellular vestibule, difference maps
      normalized by the mean of the standard deviation map can be used as a good
      approximation of the t-test map of the gap junction crystals.

PMID- 17187988
TI  - High performance computing in biology: multimillion atom simulations of nanoscale
      systems.
AB  - Computational methods have been used in biology for sequence analysis
      (bioinformatics), all-atom simulation (molecular dynamics and quantum
      calculations), and more recently for modeling biological networks (systems
      biology). Of these three techniques, all-atom simulation is currently the most
      computationally demanding, in terms of compute load, communication speed, and
      memory load. Breakthroughs in electrostatic force calculation and dynamic load
      balancing have enabled molecular dynamics simulations of large biomolecular
      complexes. Here, we report simulation results for the ribosome, using
      approximately 2.64 million atoms, the largest all-atom biomolecular simulation
      published to date. Several other nano-scale systems with different numbers of
      atoms were studied to measure the performance of the NAMD molecular dynamics
      simulation program on the Los Alamos National Laboratory Q Machine. We
      demonstrate that multimillion atom systems represent a 'sweet spot' for the NAMD
      code on large supercomputers. NAMD displays an unprecedented 85% parallel scaling
      efficiency for the ribosome system on 1024 CPUs. We also review recent targeted
      molecular dynamics simulations of the ribosome that prove useful for studying
      conformational changes of this large biomolecular complex in atomic detail.

PMID- 17187991
TI  - Movement of the hyoid bone and the epiglottis during swallowing in patients with
      dysphagia from different etiologies.
AB  - PURPOSE: (1) To compare the kinematic motion of the hyoid bone and the epiglottis
      in healthy controls and a sample of patients with dysphagia of different
      etiologies, and (2) to evaluate the potential value of kinematic swallowing
      analysis to differentiate the mechanism of dysphagia. METHODS: We performed two
      dimensional video motion analysis of the hyoid bone using videofluoroscopic
      images in nine controls without any swallowing difficulty, and seven patients
      with supratentorial stroke, three patients with inflammatory myopathy who showed
      dysphagia. Main outcome measures were: (1) horizontal and vertical excursion of
      the hyoid bone, and rotation of the epiglottis, and (2) trajectory of the hyoid
      bone and epiglottis during swallowing. RESULTS: Horizontal excursion of the hyoid
      bone and rotation of the epiglottis were reduced in patients with myopathy as
      compared to control and patients with stroke (P<0.05). Patients with dysphagia
      showed different patterns as compared to control in trajectory analysis according
      to their etiology. CONCLUSION: We conclude that extent and pattern of movement of
      the hyoid bone and the epiglottis during swallowing were different according to
      etiology of dysphagia, and swallowing motion analysis could be applied to
      differentiate the mechanism of dysphagia.

PMID- 17187992
TI  - Diminished episodic memory awareness in older adults: evidence from feeling-of
      knowing and recollection.
AB  - The ability to reflect on and monitor memory processes is one of the most
      investigated metamemory functions, and one of the important ways consciousnesses
      interacts with memory. The feeling-of-knowing (FOK) is one task used to evaluate
      individual's capacity to monitor their memory. We examined this reflective
      function of metacognition in older adults. We explored the contribution of
      metacognition to episodic memory impairment, in relation to the idea that older
      adults show a reduction in memory awareness characteristic of episodic memory. A
      first experiment showed that age affects the accuracy of FOK when predictions are
      made on an episodic memory task but not on a semantic memory task, suggesting a
      particular role for episodic memory awareness in metacognitive evaluations. A
      second experiment showed that the age-difference in episodic FOK accuracy was
      removed if one took into account subjective reports of memory awareness, or
      recollection. We argue that the FOK deficit specific to episodic memory is based
      on a lack of memory awareness manifest as a recollection deficit.

PMID- 17187993
TI  - Sustained spatial attention to vibration is mediated in primary somatosensory
      cortex.
AB  - Focusing attention to a specific body location has been shown to improve
      processing of events presented at this body location. One important debate
      concerns the stage in the somatosensory pathway at which the neural response is
      modulated when one attends to a tactile stimulus. Previous studies focused on
      components of the somatosensory evoked potential to transient stimuli, and
      demonstrated an early cortical attentional modulation. The neural basis of
      sustained spatial stimulus processing with continuous stimulation remains,
      however, largely unexplored. A way to approach this topic is to present vibrating
      stimuli with different frequencies for several seconds simultaneously to
      different body locations while subjects have to attend to the one or the other
      location. The amplitude of the somatosensory steady-state evoked potential
      (SSSEP) elicited by these vibrating stimuli increases with attention. On the
      basis of 128 electrode recordings, we investigated the topographical distribution
      and the underlying cortical sources by means of a VARETA approach of this
      attentional amplitude modulation of the SSSEP. Sustained spatial attention was
      found to be mediated in primary somatosensory cortex with no differences in SSSEP
      amplitude topographies between attended and unattended body locations. These
      result patterns were seen as evidence for a low-level sensory gain control
      mechanism in tactile spatial attention.

PMID- 17187994
TI  - Quantification of alpha4beta2* nicotinic receptors in the rat brain with microPET
      and 2-[18F]F-A-85380.
AB  - The radioligand 2-[(18)F]F-A-85380 has been used for PET studies of the
      alpha4beta2* subtype of nicotinic acetylcholine receptors (nAChRs) in the living
      brain of humans and nonhuman primates. In order to extend the capacity of
      microPET to quantify neuroreceptors in rat brain, we carried out studies of 2
      [(18)F]F-A-85380 to measure the apparent binding potential BP* in individual
      rats, which were studied repeatedly over several months. Using a bolus-plus
      infusion paradigm, 2-[(18)F]F-A-85380 (specific activity 20-1300 GBq/micromol)
      was administered intravenously over 8 to 9 h with K(bol) values of 350 to 440 min
      and a mean infusion rate of 0.03+/-0.01 nmol/kg/h. Studies included a 2-h
      nicotine infusion initiated 2 h before the end of scanning to displace
      specifically bound radioactivity. Steady state binding in brain was obtained
      within 5 h as defined by the occurrence of constant radioactivity concentrations
      in brain regions and constant, free arterial plasma levels of nonmetabolized
      radioligand. BP* averages (+/-SEM) for thalamus, forebrain, and cerebellum were
      5.9+/-0.7, 2.6+/-0.4, and 1.0+/-0.1, respectively, which are consistent with the
      alpha4beta2* nAChR distribution in rat brain measured in vitro. Studies of
      receptor occupancy determined the ED(50) to be 0.29 nmol/kg/h. The demonstration
      that alpha4beta2* nAChRs are quantifiable in the rat brain using PET
      measurements, coupled with the ability to conduct longitudinal studies over
      several months in the same rats, suggests potential applications to studies of
      chronic nicotine use, its treatment, and abnormal functioning of alpha4beta2*
      receptors in a rat model.

PMID- 17187995
TI  - Localization of individual area neuronal activity.
AB  - A family of methods, collectively known as independent component analysis (ICA),
      has recently been added to the array of methods designed to decompose a multi
      channel signal into components. ICA methods have been applied to raw
      magnetoencephalography (MEG) and electroencephalography (EEG) signals to remove
      artifacts, especially when sources such as power line or cardiac activity
      generate strong components that dominate the signal. More recently, successful
      ICA extraction of stimulus-evoked responses has been reported from single-trial
      raw MEG and EEG signals. The extraction of weak components has often been
      erratic, depending on which ICA method is employed and even on what parameters
      are used. In this work, we show that if the emphasis is placed on individual
      "independent components," as is usually the case with standard ICA applications,
      differences in the results obtained for different components are exaggerated. We
      propose instead the reconstruction of regional brain activations by combining
      tomographic estimates of individual independent components that have been
      selected by appropriate spatial and temporal criteria. Such localization of
      individual area neuronal activity (LIANA) allows reliable semi-automatic
      extraction of single-trial regional activations from raw MEG data. We demonstrate
      the new method with three different ICA algorithms applied to both computer
      generated signals and real data. We show that LIANA provides almost identical
      results with each ICA method despite the fact that each method yields different
      individual components.

PMID- 17187996
TI  - A new toolbox for combining magnetoencephalographic source analysis and
      cytoarchitectonic probabilistic data for anatomical classification of dynamic
      brain activity.
AB  - Size and location of activated cortical areas are often identified in relation to
      their surrounding macro-anatomical landmarks such as gyri and sulci. The sulcal
      pattern, however, is highly variable. In addition, many cortical areas are not
      linked to well defined landmarks, which in turn do not have a fixed relationship
      to functional and cytoarchitectonic boundaries. Therefore, it is difficult to
      unambiguously attribute localized neuronal activity to the corresponding cortical
      areas in the living human brain. Here we present new methods that are implemented
      in a toolbox for the objective anatomical identification of neuromagnetic
      activity with respect to cortical areas. The toolbox enables the platform
      independent integration of many types of source analysis obtained from
      magnetoencephalography (MEG) together with probabilistic cytoarchitectonic maps
      obtained in postmortem brains. The probability maps provide information about the
      relative frequency of a given cortical area being located at a given position in
      the brain. In the new software, the neuromagnetic data are analyzed with respect
      to cytoarchitectonic maps that have been transformed to the individual subject
      brain space. A number of measures define the degree of overlap between and
      distance from the activated areas and the corresponding cytoarchitectonic maps.
      The implemented algorithms enable the investigator to quantify how much of the
      reconstructed current density can be attributed to distinct cortical areas.
      Dynamic correspondence patterns between the millisecond-resolved MEG data and the
      static cytoarchitectonic maps are obtained. We show examples for auditory and
      visual activation patterns. However, size and location of the postmortem brain
      areas as well as the inverse method applied to the neuromagnetic data bias the
      anatomical classification. Therefore, the adaptation to the respective
      application and a combination of the objective quantities are discussed.

PMID- 17187998
TI  - Phylogenetic position of Karotomorpha and paraphyly of Proteromonadidae.

PMID- 17187997
TI  - Novel phylogeny of the raccoon family (Procyonidae: Carnivora) based on nuclear
      and mitochondrial DNA evidence.

PMID- 17187999
TI  - Obligatory group I introns with unusual features at positions 1949 and 2449 in
      nuclear LSU rDNA of Didymiaceae myxomycetes.
AB  - Myxomycetes (plasmodial slime molds) belonging to the order Physarales contain
      obligatory group I introns at positions 1949 and 2449 in their large subunit
      ribosomal RNA gene. Here, we report 36 group I introns from the Didymiaceae
      family (order Physarales) from 18 isolates representing three genera and seven
      species, and have reconstructed both host and intron phylogenies. The introns,
      named L1949 and L2449, were found in all isolates analyzed, consistent with an
      obligatory distribution in Didymiaceae. The introns fold at the RNA-level into
      typical group I ribozyme core structures that are relatively conserved, but
      contain large and highly variable extension sequences in peripheral domains
      without any detectable protein coding capacities. Furthermore, the L1949 and
      L2449 introns have probably become dependent on host factors for folding or
      activity. This assumption is based on that all introns tested for self-splicing
      in vitro failed to ligate the flanking exon regions. Phylogenies based on LSU
      rDNA and intron sequences are consistent with that the L1949 and L2449 introns
      follow a strict vertical inheritance within Didymiaceae. We suggest that the
      Didymiaceae L1949 and L2449 introns are well suited as high-resolution markers in
      genetic assessments at various taxonomic levels, from closely related strains of
      a single species to separating genera.

PMID- 17188000
TI  - Divergent paralogues of ribosomal DNA in eucalypts (Myrtaceae).
AB  - The presence of divergent paralogues of nuclear ribosomal DNA, from the 18S-5.8S
      26S cistron, is reported in members of Eucalyptus subg. Eucalyptus. These
      paralogues, which include non-functional pseudogenes, probably diverged prior to
      the differentiation of species groups in subg. Eucalyptus. When compared with
      presumably functional sequences, the pseudogenes show greater sequence variation
      between species, particularly in the 5.8S gene. They are also characterised by
      reduced GC content, associated with a reduced number of CpG and CpNpG methylation
      sites, and an increase in the inferred number of methylation-induced
      substitutions. Some pseudogenes also lack motifs that are usually conserved in
      plants, both in ITS1 and the 5.8S gene. Two main lineages of pseudogenes are
      identified, one isolated from a group of western Australian species, one from a
      group of eastern Australian species. It is not clear whether these two lineages
      of pseudogenes are orthologous, or represent independent divergences from
      functional sequence types. The presence of divergent rDNA paralogues highlights
      the need for caution when interpreting eucalypt phylogenies based on ITS
      sequences.

PMID- 17188001
TI  - Reassessment of the classification of the Order Haplosclerida (Class
      Demospongiae, Phylum Porifera) using 18S rRNA gene sequence data.

PMID- 17188002
TI  - Phylogenetic relationships of some common Indo-Pacific snappers (Perciformes:
      Lutjanidae) based on mitochondrial DNA sequences, with comments on the taxonomic
      position of the Caesioninae.
AB  - The phylogenetic relationships of 27 species of common Indo-Pacific snappers
      (Lutjanidae) were explored using the 16S ribosomal RNA and cytochrome b
      mitochondrial genes with minimum evolution, maximum parsimony, maximum likelihood
      and Bayesian inference analyses. Included were species representing four
      subfamilies, the Caesioninae, Etelinae, Paradicichthyinae, and Lutjaninae.
      Members of the closely related families Haemulidae, Lethrinidae, Nemipteridae and
      Sparidae, were included for outgroup comparisons and to explore the relationships
      between the Haemuloidea, Lutjanoidea and Sparoidea. Monophyly of the Lutjanidae
      was resolved. The Caesioninae was nested within the Lutjaninae, supporting the
      recent view that the Caesionidae should be treated as a synonym of the
      Lutjanidae. The subfamilies Etelinae and Paradicichthyinae were resolved as
      sister taxa to the remainder of the Lutjanidae, which corroborates previous
      cladistic analyses conducted to determine relationships of lutjanid subfamilies.
      Bayesian inference and maximum likelihood analyses suggest that Macolor is the
      sister taxon to the Caesioninae and may represent a transitional form between the
      Lutjaninae and Caesioninae. Three species of Western Atlantic lutjanids, Lutjanus
      campechanus, L. synagris, and Rhomboplites aurorubens, were included in the
      analyses to examine their relationships to Indo-Pacific species; they formed a
      well-supported clade nested within Pacific lutjanines suggesting that Atlantic
      species of Lutjaninae are derived from an Indo-Pacific lineage. Results of our
      molecular phylogenetic analyses are congruent with the general morphology and
      external colouration of the resolved groups of species of Lutjanus. The "black
      spot" complex containing L. fulviflamma, L. monostigma, and L. russelli was
      resolved with strong support, and had L. carponotatus nested within. The
      morphology of L. carponotatus suggests a close relationship to this group, and
      the lack of the black spot near the lateral line below the soft dorsal fin is
      possibly a secondary loss. As expected, the "blue-lined" species, L. kasmira and
      L. quinquelineatus, formed a strongly supported clade. Lutjanus bohar and L.
      gibbus, both distinctly red, long-lived fish that often accumulate large
      quantities of ciguatera toxin in their tissues, were resolved as sister taxa.

PMID- 17188003
TI  - The relationship between paired pulse magnetic MEP and surgical prognosis in
      patients with intractable epilepsy.
AB  - PURPOSE: To assess whether paired pulse magnetic motor evoked potential (MEP) can
      predict surgical prognosis in patients with intractable epilepsy. METHODS: MEP of
      the unilateral hand muscles were recorded following paired pulse transcranial
      magnetic stimulation (TMS) of the motor cortex. The interstimulus intervals of
      paired stimulation were 1-16 ms with a conditioning stimulus that was 90% active
      motor threshold. Subjects were six patients with temporal lobe epilepsy (TLE)
      scheduled for anterior temporal lobectomy and three patients with myoclonic or
      head-drop seizures scheduled for anterior corpus callosotomy, resulting in the
      unilateralization of epileptic discharges. The hemisphere showing unilateral
      discharges was defined as the affected hemisphere. The intracortical inhibition
      and facilitation curve was drawn based on MEP before and after surgery and the
      relationship between MEP and surgical prognosis was investigated. RESULTS: In
      five patients with TLE showing class I surgical results (Engel's classification),
      the affected hemisphere showing cortical hyperexcitability preoperatively was
      almost normalized after surgery. However, in a patient with class III, the
      unaffected hemisphere showed cortical hyperexcitability before and after surgery.
      In the callosotomy group, two patients with excellent outcomes showed the same
      results as TLE group with class I. CONCLUSIONS: Paired pulse magnetic MEP may
      provide predictive value in terms of surgical outcome in those patients with
      intractable epilepsy.

PMID- 17188004
TI  - Cytoplasmic pH-dependent spreading of polymorphonuclear leukocytes: regulation by
      pH of PKC subcellular distribution and F-actin assembly.
AB  - Cytoplasmic pH (pHi) plays an important role in the regulation of
      polymorphonuclear leukocyte (PMN) spreading, but the molecular mechanisms
      involved have long been obscure. In the present study, we investigated the pH
      dependence of phorbol myristate acetate (PMA)-induced PMN spreading. A change in
      pHi alone did not induce spreading, but cytoplasmic alkalinization promoted the
      spreading induced by PMA, whereas acidification inhibited it. To further
      investigate the mechanism by which pHi affects cell spreading, we employed
      subcellular fractionation and immunoblot analyses to evaluate the effect of pH on
      the subcellular distribution of protein kinase C (PKC) and assembly of the actin
      cytoskeleton. We found that cytoplasmic alkalinization enhanced PKC membrane
      distribution and quantitatively up-regulated the actin cytoskeleton. On the other
      hand, cytoplasmic acidification was found to have effects on these signaling
      molecules that were opposite to those of cytoplasmic alkalinization. These
      results may provide a potential explanation for the pH-regulation of the PMA
      induced PMN spreading.

PMID- 17188005
TI  - Full activation of the T cell receptor requires both clustering and
      conformational changes at CD3.
AB  - T cell receptor (TCR-CD3) triggering involves both receptor clustering and
      conformational changes at the cytoplasmic tails of the CD3 subunits. The
      mechanism by which TCRalphabeta ligand binding confers conformational changes to
      CD3 is unknown. By using well-defined ligands, we showed that induction of the
      conformational change requires both multivalent engagement and the mobility
      restriction of the TCR-CD3 imposed by the plasma membrane. The conformational
      change is elicited by cooperative rearrangements of two TCR-CD3 complexes and
      does not require accompanying changes in the structure of the TCRalphabeta
      ectodomains. This conformational change at CD3 reverts upon ligand dissociation
      and is required for T cell activation. Thus, our permissive geometry model
      provides a molecular mechanism that rationalizes how the information of ligand
      binding to TCRalphabeta is transmitted to the CD3 subunits and to the
      intracellular signaling machinery.

PMID- 17188006
TI  - Exploring the mechanism of protein synthesis with modified substrates and novel
      intermediate mimics.
AB  - Translation, the synthesis of proteins from individual amino acids based on
      genetic information, is a cornerstone biological process. During ribosomal
      protein synthesis, new peptide bonds form through aminolysis of the peptidyl-tRNA
      ester bond by the alpha-amino group of the A-site amino acid. The rate of this
      reaction is accelerated at least 10(7)-fold in the ribosome, but the catalytic
      mechanism has remained controversial. We have used a combination of synthetic
      chemistry, biochemical, and structural biology approaches to characterize the
      mechanism of the peptidyl transfer reaction and the configuration of the
      reaction's tetrahedral intermediate. Substitution of the P-site tRNA A76 2' OH
      with 2' H or 2' F results in at least a 10(6)-fold reduction in the rate of
      peptide bond formation, but does not affect binding of the modified substrates.
      This indicates that the 2'-OH is essential to the reaction through participation
      in substrate assisted catalysis. A series of novel mimics of the tetrahedral
      intermediate were examined to distinguish between possible regio- and
      stereoisomeric forms of the intermediate. The determination of these parameters
      has important implications for the configuration of the substrates and
      intermediate within the ribosomal active site, and thus which functional groups
      are properly positioned to play various roles in promoting the reaction. Our
      results contribute to an emerging model of the peptidyl transfer reaction in
      which the ribosomal active site positions the substrates in an orientation
      specifically designed to promote the reaction, wherein the A76 2'-OH serves as a
      proton shuttle to enable critical proton transfers in the formation of the final
      peptide product.

PMID- 17188009
TI  - A study of tablet dissolution by magnetic resonance electric current density
      imaging.
AB  - The electric current density imaging technique (CDI) was used to monitor the
      dissolution of ion releasing tablets (made of various carboxylic acids and of
      sodium chloride) by following conductivity changes in an agar-agar gel
      surrounding the tablet. Conductivity changes in the sample were used to calculate
      spatial and temporal changes of ionic concentrations in the sample. The
      experimental data for ion migration were compared to a mathematical model based
      on a solution of the diffusion equation with moving boundary conditions for the
      tablet geometry. Diffusion constants for different acids were determined by
      fitting the model to the experimental data. The experiments with dissolving
      tablets were used to demonstrate the potential of the CDI technique for
      measurement of ion concentration in the vicinity of ion releasing samples.

PMID- 17188007
TI  - Acute disseminated encephalomyelitis cohort study: prognostic factors for
      relapse.
AB  - To date, there is no available epidemiological study about prognostic factors of
      acute disseminated encephalomyelitis (ADEM) in children, using a cohort of
      patients with homogenous inclusion criteria. We aimed to evaluate prognostic
      factors for relapse after ADEM in children. A total of 132 children from the
      French National KIDSEP Neuropediatric Cohort (mean age at onset: 6+/-3.3 years;
      mean follow-up: 5.4+/-3.3 years; lost to follow-up: 10%). ADEM diagnosis was
      considered in a previously healthy patient acutely presenting more than one
      neurological deficit, change in mental state and MRI alterations including white
      matter changes. We used multivariate survival analysis (Cox model) evaluating the
      prognostic value of baseline clinical, biological and MRI covariates, for the
      occurrence of a second attack. Twenty-four (18%) of included patients had a
      second attack. An increased risk of relapse was associated with optic neuritis
      (hazard ratio, 5.23; 95% CI, 2-13.65), familial history of central nervous system
      inflammatory demyelination (7.79; 1.54-39.5), Barkhof multiple sclerosis (MS)
      criteria on MRI (2.52; 1.04-6.12) and no neurological sequelae after first attack
      (3.79; 1.12-12.85). Clinical and MRI prognostic factors for relapse in ADEM may
      contribute to an early distinction between monophasic and relapsing disease,
      which may be related to MS.

PMID- 17188008
TI  - Spin pair geometry revealed by high-field DEER in the presence of conformational
      distributions.
AB  - Orientation selection on two nitroxide-labelled shape-persistent molecules is
      demonstrated by high-field pulsed electron-electron double resonance experiments
      at a frequency of 95 GHz with a commercial spectrometer. The experiments are
      performed with fixed observer and pump frequencies by variation of the magnetic
      field, so that the variation of both the dipolar frequencies and the modulation
      depths can be analyzed. By applying the deadtime-free four-pulse double electron
      electron resonance (DEER) sequence, the lineshapes of the dipolar spectra are
      obtained. In the investigated linear biradical and equilateral triradical the
      nitroxide labels undergo restricted dynamics, so that their relative orientations
      are not fixed, but are correlated to some extent. In this situation, the general
      dependence of the dipolar spectra on the observer field can be satisfyingly
      modelled by simple geometrical models that involve only one rotational degree of
      freedom for the biradical and two rotational degrees of freedom for the
      triradical. A somewhat better agreement of the dipolar lineshapes for the
      biradical is obtained by simulations based on a molecular dynamics trajectory.
      For the triradical, small but significant deviations of the lineshape are
      observed with both models, indicating that the technique can reveal deficiencies
      in modelling of the conformational ensemble of a macromolecule.

PMID- 17188010
TI  - Activation and repolarization patterns in the ventricular epicardium under sinus
      rhythm in frog and rabbit hearts.
AB  - Our study compared the contributions of activation sequence and local
      repolarization durations distribution in the organization of epicardial
      repolarization in animals with fast (rabbit) and slow (frog) myocardial
      activation under sinus rhythm. Activation times, repolarization times and
      activation-recovery intervals (ARI) were obtained from ventricular epicardial
      unipolar electrograms recorded in 13 Chinchilla rabbits (Oryctolagus cuniculus)
      and 10 frogs (Rana temporaria). In frogs, depolarization travels from the
      atrioventricular ring radially. ARIs increased progressively from the apex to the
      middle portion and finally to the base (502+/-75, 557+/-73, 606+/-79 ms,
      respectively; P<0.01). In rabbits, depolarization spread from two epicardial
      breakthroughs with the duration of epicardial activation being lower than that in
      frogs (17+/-3 vs. 44+/-18 ms; P<0.001). ARI durations were 120+/-37, 143+/-45,
      and 163+/-40 ms in the left ventricular apex, left, and right ventricular bases,
      respectively (P<0.05). In both species, repolarization sequence was directed from
      apex to base according to the ARI distribution with dispersion of repolarization
      being higher than that of activation (P<0.001). Thus, excitation spread sequence
      and velocity per se do not play a crucial role in the formation of ventricular
      epicardial repolarization pattern, but the chief factor governing repolarization
      sequences is the distribution of local repolarization durations.

PMID- 17188011
TI  - Induction and partial characterization of California halibut (Paralichthys
      californicus) vitellogenin.
AB  - The egg yolk precursor protein, vitellogenin (Vg), was isolated by size exclusion
      and ion exchange chromatography from plasma of California halibut (Paralichthys
      californicus) treated with estrogen. MALDI TOF mass spectrometry (MS) analysis
      resulted in a molecular mass of 188 kDa. MS/MS de novo sequencing identified the
      protein as Vg by matching sequences of tryptic peptides to the known sequences of
      several other species. Matches were also made to two different forms of Vg in
      haddock, medaka, and mummichog, providing evidence that California halibut has
      more than one form of Vg. Native PAGE and Western blot with an antibody to turbot
      (Scophthalmus maximus) Vg confirmed the identity of the protein. Protein resolved
      on the SDS PAGE as a double band of approximately the same mass as determined
      with MALDI TOF, and two lower mass bands that were also immunoreactive. MALDI TOF
      and MS/MS de novo sequencing were useful for determining the molecular mass,
      identification, and exploring the multiplicity of Vg. The potential of using
      other MS methods to understand the structure and function of Vg is discussed.

PMID- 17188012
TI  - Lactate uptake by skeletal bone in anoxic turtles, Trachemys scripta.
AB  - Previous studies have shown that freshwater turtle shells can accumulate lactate
      during periods of anoxic submergence. Our objective in this study was to
      determine lactate uptake in other parts of the turtle's skeleton. We measured
      lactate concentration of 7 skeletal elements and 4 shell samples of red-eared
      slider turtles, Trachemys scripta, in control animals (N=12) and in animals
      following submergence for 4-5 days in N(2)-equilibrated water at 10 degrees C
      (N=8). We also collected blood samples and measured blood pH, PCO(2), and PO(2),
      and plasma lactate. Contralateral bone samples from 6 control turtles were
      analyzed for % water and mineral composition; bone from the other 6 were
      equilibrated with lactate solution in vitro. Anoxic submergence resulted in a
      combined respiratory/non-respiratory (lactic) acidosis and plasma lactate of
      45.6+/-2.5 mmol l(-1). Shell and skeletal lactates all increased significantly in
      the anoxic animals (30.1-43.9 mmol kg(-1)) with limb bones having the highest
      levels and skull the least. Skeletal samples equilibrated in lactate solution in
      vitro for 2 days accumulated lactate in similar fashion with limb bones, except
      for fibula, higher, and skull significantly less than other bones. We conclude
      that the entire skeleton of the red-eared slider, like its shell, sequesters
      lactate and contributes thereby to lactic acid buffering.

PMID- 17188013
TI  - Incidence of and risk factors for cat bites: a first step in prevention and
      treatment of feline aggression.
AB  - Feline aggression towards people has a smaller incidence than canine aggression,
      but also represents an important public health problem. The aim of this work was
      to analyse feline aggression reported towards people, to estimate its incidence
      and to assess the risk factors involved. The information was obtained from the
      Public Health Centres in the Valencian Region (Spain). A total of 936 acts of
      feline aggression were analysed. Cats inflicted 8% of all animal bites reported.
      The annual average was 6.36 feline aggression incidents per 100,000 people. Most
      aggressive incidents occurred during the summer months. Children (0-14 years old)
      and women were more likely to be bitten. Wounds were mainly punctures, single,
      and mild, and were located mostly on the hands. In children, the head and neck
      areas were affected much more than in adults. The cats involved in incidents were
      mostly Siamese, female and owned; these cats mainly attacked their owners. Most
      occurrences were a defensive response by the cat.

PMID- 17188014
TI  - [Is there a role for X-ray pelvimetry in the twenty-first century?].
AB  - The purpose of this article was to perform a critical analysis of publications
      having estimated the utility of X-ray pelvimetry, in order to allow tangible and
      useful conclusions for the clinical practice. X-ray pelvimetry was proposed in 3
      indications: trial of labour among patients with a history of caesarean section,
      breech presentation, suspicion of cephalopelvic disproportion. The large majority
      of these publications are retrospective studies, studying a low number of
      patients and especially without control groups or randomisation. Their
      contradictory results and their methodological weaknesses do not allow any
      conclusion. Published randomised trials are exceptional. Among patients with a
      history of caesarean section, there is only one randomised trial; it demonstrates
      that ante-partum X-ray pelvimetry is not necessary prior to a trial labour in
      women with one previous caesarean section. It increases the caesarean section
      rate and is a poor predictor of the outcome of labour. There is also only one
      randomised trial which evaluated the interest of X-ray pelvimetry in patients
      with a breech presentation: the use of pelvimetry in breech presentation at term
      does not significantly reduce the overall caesarean-section rate, and does not
      improve the neonatal issues. However, it allows better selection of the delivery
      route, with a significantly lower emergency Caesarean-section rate. Finally, the
      only one randomised trial having studied the utility of X-ray pelvimetry for the
      prediction of cephalopelvic disproportion shows that pelvimetry is a poor
      predictor of the outcome of labour, has no influence on the neonatal issues and
      increases the caesarean sections rate. Furthermore, although radiation exposure
      during a X-ray pelvimetry is very weak, diagnostic X-ray studies during any stage
      of gestation have been shown to increase the risk of childhood cancer in the
      irradiated fetus. In the rare cases where pelvimetry is useful (trial of labour
      with a breech presentation), it is thus careful to perform a MRI pelvimetry.

PMID- 17188015
TI  - Method for comparing the efficiency of ultrasound irradiation independent of the
      shape and the volume of the reaction vessel in sonochemical experiments.
AB  - The method described herein this review compares the efficiency of ultrasound
      irradiation in sonochemical experiments in organic solvents. This method was
      shown to be independent of the shape and volume of the reaction vessel. The
      principle of this method is based on the fact that the concentration of dissolved
      oxygen in the entire reaction volume during acoustic cavitation depends on the
      ultrasound power or intensity of ultrasound field respectively. The concentration
      of dissolved oxygen is determined by the measurement of the fluorescence
      intensity with fluorescence probes.

PMID- 17188016
TI  - Folding, activity and targeting of mutated human cathepsin D that cannot be
      processed into the double-chain form.
AB  - The precursor of human cathepsin D (CD) is converted into the single-chain and
      the double-chain active polypeptides by subsequent proteolysis reactions taking
      place in the endosomal-lysosomal compartment and involving specific aminoacid
      sequences. We have mutagenized the region of aminoacids (comprising the beta
      hairpin loop) involved in the latter proteolytic maturation step and generated a
      mutant CD that cannot be converted into the mature double-chain form. This mutant
      CD expressed in rodent cells reaches the lysosome and is stable as single-chain
      polypeptide, bears high-mannose type sugars, binds to pepstatin A and is
      enzymatically active, indicating that it is correctly folded. The present work
      provides new insights on the aminoacid region involved in the terminal processing
      of human CD and on the function of the processing beta-hairpin loop.

PMID- 17188017
TI  - Reverse geometry contact lens fitting in corneal scar caused by perforating
      corneal injuries.
AB  - PURPOSE: To describe a reverse geometry rigid gas permeable (RGP) contact lens
      fitting in corneal scar caused by perforating corneal injuries with intraocular
      strange body. METHODS: A reverse geometry RGP lens, with large diameter, was
      empirically fitted in a 38-year-old male patient who had previous open globe
      injuries due to work accident in right eye. Corneal suture, vitrectomy and lens
      extraction were performed. Irregular corneal surface with corneal scar in line
      with the visual axis were found with low uncorrected visual acuity. RESULTS:
      Snellen visual acuity improved from counterfinger to 0.8 with high contact lens
      acceptance, 6-9h per day of wear. Only three diagnostic contact lenses, in two
      visits, were necessary. Orbscan simulated fluorescein pattern was different to
      definitive fluorescein pattern. CONCLUSIONS: Reverse geometry RGP contact lens,
      with large diameters, could be a good alternative in irregular corneal surface
      with corneal scar. Fluorescein pattern analysis could be the proper fitting
      technique. This fitting could involve less time and fewer visits. Computer-aided
      fitting was of limited value in these cases.

PMID- 17188018
TI  - Comparison of the Kato-Katz technique, hatching test and indirect
      hemagglutination assay (IHA) for the diagnosis of Schistosoma japonicum infection
      in China.
AB  - The Kato-Katz technique (duplicate 41.7 mg fecal smears), hatching test and
      indirect hemagglutination assay (IHA) were compared for their ability to detect
      human Schistosoma japonicum infection in two endemic villages (Zhonjiang and
      Zhuxi) in rural China. The hatching test (using a nylon bag, and based on about
      30 g of feces) and IHA are conventional Chinese diagnostic methods. In both
      villages, the trends of prevalences with age and sex were comparable for the
      different methods. In Zhuxi, Kato-Katz examinations of stools from 7 different
      days and hatching were available, which could be used as a reliable gold
      standard. This resulted for IHA in a sensitivity of 80% and a specificity of 48%.
      The sensitivity of the Kato-Katz technique using one stool specimen was 68%,
      twice that of hatching (33%). In Zhonjiang, however, hatching resulted in more
      positive cases than Kato-Katz (prevalence 31% vs. 24%). Apparently, the result of
      the hatching test depends on environmental factors such as temperature and water
      quality. Although imperfect, Kato-Katz is recommended out of the three evaluated
      techniques as the method of choice for large-scale screening of S. japonicum.
      Hatching is much more tedious, provides inconsistent and only qualitative
      results, and is not much more sensitive than Kato-Katz. Its poor specificity
      makes IHA unsuitable for individual screening, but it may be more effective for
      community diagnosis.

PMID- 17188019
TI  - Self-assessed symptoms in chronic heart failure--important information for
      clinical management.
AB  - AIM: To compare the patients' self-assessment of the severity of their symptoms
      with a physicians assessment and to evaluate the ability of self-assessed
      symptoms and ejection fraction (EF) to predict long-term survival in heart
      failure patients. METHOD: Patients (n=332) evaluated symptoms using a self
      administered functional classification scale (Specific Activity Scale, SAS),
      which is equivalent to the NYHA scale. EF and NYHA functional class was also
      recorded. All patients were followed over a 3-year period. RESULTS: Approximately
      50% of patients classified themselves into SAS class I. In contrast, the
      cardiologists classified only 9% of the patients as NYHA class I. In patients
      with severe left ventricular dysfunction (EF<or=0.35) SAS score (HR 1.48, 95% CI
      [1.03-2.12] p=0.03) and ACE inhibitor treatment (0.23 [0.11-0.51], p=0.0003)
      independently predicted 3-year mortality in a multivariable analysis. EF was not
      predictive of mortality in the low EF group. Only age predicted long-term outcome
      in patients with preserved systolic function. CONCLUSION: Patients' self-assessed
      symptoms and NYHA classification are not coherent. Left ventricular EF is of less
      importance in comparison with symptoms in chronic heart failure. Patients
      reporting less severe symptoms had a favourable 3-year prognosis, regardless of
      EF.

PMID- 17188020
TI  - Characterization of health-related quality of life in heart failure patients with
      preserved versus low ejection fraction in CHARM.
AB  - BACKGROUND: Limited comparative studies assessing the health-related quality of
      life (HRQL) in heart failure (HF) patients with preserved vs. low ejection
      fraction (LVEF) have been disparate. AIMS: The aims of this study were a) to
      characterize HRQL in a large population of HF patients with preserved and low
      LVEF and b) to determine the factors associated with worse HRQL. METHODS:
      Patients with symptomatic HF (NYHA Class II-IV) enrolled in the Candesartan in
      Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) HRQL
      study completed the Minnesota Living with Heart Failure questionnaire at
      randomization. Patients were stratified into 2 HF cohorts: preserved LVEF (>40%)
      and low LVEF (<or=40%). RESULTS: In 2709 of the eligible 2744 (98.6%) patients,
      the summary scores ranged from 0 to 105 (mean 40.9). There were no differences in
      overall responses of HF patients with preserved vs. low LVEF (41.1 vs. 40.8).
      Independent factors associated with worse HRQL in both populations included
      female gender, younger age, higher body mass index, lower systolic blood
      pressure, greater symptom burden, and worse functional status. CONCLUSIONS: In
      symptomatic HF patients, HRQL is equally impaired in both preserved and low LVEF
      populations. Targeting improvement in symptoms and HRQL is an important treatment
      objective in all HF patients.

PMID- 17188021
TI  - Diagnostic relevance of the determination of lymphocyte subpopulations in
      environmental medicine.
AB  - Earlier hopes that determination of lymphocyte subpopulations might become a
      strong diagnostic tool in environmental medicine have not been fulfilled in
      recent years. Analysis of the scientific literature rather shows that there are
      only few examples for environmental exposures causing reproducible shifts of
      lymphocyte subpopulations. Moreover, current knowledge suggests that
      "environmental diseases" are not associated with characteristic changes of
      subpopulation patterns. If lymphocyte subpopulations are analyzed, each
      diagnostic step, including indication, sample handling, analytic procedure and
      data-interpretation, should adhere to good quality criteria. Taking all together,
      the determination of lymphocyte subpopulations in the context of environmental
      medicine comes under category IV of the criteria of the Commission for Methods
      and Quality Assurance in Environmental Medicine of the German federal health
      authority (Robert Koch-Institute; RKI): "A procedure cannot be recommended
      because there is not sufficient information to justify it" (here: no solid trends
      in epidemiological examinations), "and because theoretical considerations speak
      against an application" (here: high physiological variability and missing
      exposure or substance specificity).

PMID- 17188022
TI  - Neurodevelopmental origins of depressive disorders.
AB  - Depression is a common and devastating neuropsychiatric disorder, and a better
      understanding of its pathophysiology is needed to improve diagnosis, treatment
      and prevention. By considering the developmental dimensions of genetic and
      environmental factors, new insights have been found into the etiology and
      pathophysiology of depression. Specifically, we begin to understand how certain
      vulnerability factors affect the maturation of brain circuits involved in
      emotional function to increase the risk for depressive disorders later in life.
      These new findings might help us to better categorize and manage this complex
      disease.

PMID- 17188024
TI  - School-health-based parasite control initiatives: extending successful Japanese
      policies to Asia and Africa.
AB  - Japan controlled its major parasitic diseases by the 1970s. Based on this
      experience, the Government of Japan proposed the Global Parasite Control
      Initiative in 1998 and established three research and training centres around the
      world. The Asian Centre of International Parasite Control (ACIPAC) is the first
      such centre, and completed five years of activities focused on school-health
      based parasite control in the Greater Mekong Subregion in 2005. The lessons
      learned and experiences gained by ACIPAC should be applied to all health
      promotion programmes worldwide.

PMID- 17188025
TI  - Mega-trials vs. meta-analysis: precision vs. heterogeneity?
AB  - In recent years, several authors have suggested there is a need for more very
      large or "mega-trials" (defined in this manuscript as a trial powered to address
      subgroup differences/interactions/secondary analyses) to answer important
      clinical questions. Because mega-trials are expensive and funding for clinical
      research is limited, increasing the number of mega-trials limits funding for
      other research. The advantages of this approach compared with funding more
      focused RCTs needs to be debated. Because there is no method to determine gold
      standard for which method gives the correct answer, we provide theoretical
      arguments that demonstrate that the two approaches are similar with respect to
      sample size requirements and the mega-trial approach provides a small advantage
      with respect to minimizing confounding by chance. However, the inherent
      heterogeneity in a series of smaller trials may represent a significant advantage
      over a single mega-trial.

PMID- 17188026
TI  - Altered DNA damage response in Caenorhabditis elegans with impaired poly(ADP
      ribose) glycohydrolases genes expression.
AB  - Poly(ADP-ribosyl)ation is one of the first cellular responses induced by DNA
      damage. Poly(ADP-ribose) is rapidly synthesized by nick-sensor poly(ADP-ribose)
      polymerases, which facilitate DNA repair enzymes to process DNA damage. ADP
      ribose polymers are rapidly catabolized into free ADP-ribose units by poly(ADP
      ribose) glycohydrolase (PARG). The metabolism of poly(ADP-ribose) is a well
      defined biochemical process for which a physiological role in animals is just
      beginning to emerge. Two Caenorhabditis elegans PARGs, PME-3 and PME-4, have been
      cloned by our group. The pme-3 gene encodes an enzyme of 89kDa having less than
      18% overall identity with human PARG but 42% identity with the PARG signature
      motif. The pme-4 gene codes for a PARG of 55kDa with approximately 22% overall
      identity with human PARG and 40% identity with the PARG signature motif. Two
      alternatively spliced forms of PME-3 were identified with an SL1 splice leader on
      both forms of the mRNA and were found to be expressed throughout the worm's life
      cycle. Similarly, pme-4 was shown to be expressed in all developmental stages of
      the worm. Recombinant enzymes that were expressed in bacteria displayed a PARG
      activity that may partly account for the PARG activity measured in the total worm
      extract. Reporter gene analysis of pme-3 and pme-4 using a GFP fusion construct
      showed that pme-3 and pme-4 are mainly expressed in nerve cells. PME-3 was shown
      to be nuclear while PME-4 localized to the cytoplasm. Worms with pme-3 and pme-4
      expression knocked-down by RNAi showed a significant sensitivity toward ionizing
      radiations. Taken together, these data provide evidence for a physiological role
      for PARGs in DNA damage response and survival. It also shows that PARGs are
      evolutionarily conserved enzymes and that they are part of an ancient cellular
      response to DNA damage.

PMID- 17188027
TI  - Multi-organ system model of O2 and CO2 transport during isocapnic and
      poikilocapnic hypoxia.
AB  - A multi-organ systems model of O(2) and CO(2) transport is developed to analyze
      the control of ventilation and blood flow during hypoxia. Among the aspects of
      the control processes that this model addressed are possible mechanisms
      responsible for the second phase of the ventilatory hypoxic response to mild
      hypoxia, i.e., hypoxic ventilatory decline (HVD). Species mass transport
      processes are described by compartmental mass balances in brain, heart, skeletal
      muscle, and "other tissues" connected in parallel via the circulation. In
      pulmonary and systemic capillaries and in the vasculature connecting the systemic
      tissues, species transport processes are represented by a one-dimensional,
      convection-dispersion model. The effects of bicarbonate acid-base buffering,
      hemoglobin, and myoglobin on the transport processes are included. The model
      incorporates feedback control mechanisms through a cardiorespiratory control
      system in which peripheral and central chemoreceptors sense O(2) and CO(2)
      partial pressures. Model simulations of the ventilatory responses to isocapnic
      and poikilocapnic hypoxia show two phases with distinct dynamics. A fast phase is
      discernable immediately after switching from normoxic to hypoxic conditions,
      while a delayed slow phase (HVD) typically becomes manifested after several
      minutes. Model simulations allow quantitative evaluation of several proposed
      mechanisms to account for HVD. Under isocapnic hypoxia, simulations indicate that
      an increase in brain blood flow has no effect on HVD, but that HVD can be
      entirely described by central ventilatory depression (CVD). Under poikilocapnic
      hypoxia, the hypocapnia caused by hypoxic hyperventilation has no effect on HVD.

PMID- 17188028
TI  - Grabbing Plk1 by the PBD.
AB  - A new centromeric protein termed PBIP1 was identified that recruits Plk1 to the
      kinetochores. In the November 3 issue of Molecular Cell, show that Plk1
      phosphorylates PBIP1 on threonine 78, creating its own high-affinity docking site
      for the polo-box domain (PBD).

PMID- 17188029
TI  - When CDK1 rides the telomere cycle.
AB  - Reconstitution of telomeric DNA at each cell division implies the coordination of
      DNA semiconservative replication with several processing events still poorly
      understood. Two reports published recently in Molecular Cell show that a cell
      cycle cyclin-dependent kinase, Cdk1p, is required to create the cell-cycle
      regulated overhang ().

PMID- 17188030
TI  - New functions for Y family polymerases.
AB  - The Y family of DNA polymerases plays crucial roles in carrying out translesion
      synthesis past damaged bases in DNA. Several recent papers suggest that they
      might have other roles as well in gene conversion, in nucleotide excision repair
      (NER), and in DNA replication under stressed conditions.

PMID- 17188031
TI  - RNAi screen in mouse astrocytes identifies phosphatases that regulate NF-kappaB
      signaling.
AB  - Regulation of NF-kappaB activation is controlled by a series of kinases; however,
      the roles of phosphatases in regulating this pathway are poorly understood. We
      report a systematic RNAi screen of phosphatases that modulate NF-kappaB activity.
      Nineteen of 250 phosphatase genes were identified as regulators of NF-kappaB
      signaling in astrocytes. RNAi selectively regulates endogenous chemokine and
      cytokine expression. Coimmunoprecipitation identified associations of distinct
      protein phosphatase 2A core or holoenzymes with the IKK, NF-kappaB, and TRAF2
      complexes. Dephosphorylation of these complexes leads to modulation of NF-kappaB
      transcriptional activity. In contrast to IKK and NF-kappaB, TRAF2 phosphorylation
      has not been well elucidated. We show that the Thr117 residue in TRAF2 is
      phosphorylated following TNFalpha stimulation. This phosphorylation process is
      modulated by PP2A and is required for TRAF2 functional activity. These results
      provide direct evidence for TNF-induced TRAF2 phosphorylation and demonstrate
      that phosphorylation is regulated at multiple levels in the NF-kappaB pathway.

PMID- 17188032
TI  - Crystal structure of pseudouridine synthase RluA: indirect sequence readout
      through protein-induced RNA structure.
AB  - RluA is a dual-specificity enzyme responsible for pseudouridylating 23S rRNA and
      several tRNAs. The 2.05 A resolution structure of RluA bound to a substrate RNA
      comprising the anticodon stem loop of tRNA(Phe) reveals that enzyme binding
      induces a dramatic reorganization of the RNA. Instead of adopting its canonical U
      turn conformation, the anticodon loop folds into a new structure with a reverse
      Hoogsteen base pair and three flipped-out nucleotides. Sequence conservation, the
      cocrystal structure, and the results of structure-guided mutagenesis suggest that
      RluA recognizes its substrates indirectly by probing RNA loops for their ability
      to adopt the reorganized fold. The planar, cationic side chain of an arginine
      intercalates between the reverse-Hoogsteen base pair and the bottom pair of the
      anticodon stem, flipping the nucleotide to be modified into the active site of
      RluA. Sequence and structural comparisons suggest that pseudouridine synthases of
      the RluA, RsuA, and TruA families employ an equivalent arginine for base
      flipping.

PMID- 17188033
TI  - DNA translocation and loop formation mechanism of chromatin remodeling by SWI/SNF
      and RSC.
AB  - ATP-dependent chromatin-remodeling complexes (remodelers) modulate gene
      transcription by regulating the accessibility of highly packaged genomic DNA.
      However, the molecular mechanisms involved at the nucleosomal level in this
      process remain controversial. Here, we monitor the real-time activity of single
      ySWI/SNF or RSC complexes on single, stretched nucleosomal templates under
      tensions above 1 pN forces. We find that these remodelers can translocate along
      DNA at rates of approximately 13 bp/s and generate forces up to approximately 12
      pN, producing DNA loops of a broad range of sizes (20-1200 bp, average
      approximately 100 bp) in a nucleosome-dependent manner. This nucleosome-specific
      activity differs significantly from that on bare DNA observed under low tensions
      and suggests a nucleosome-remodeling mechanism through intranucleosomal DNA loop
      formation. Such loop formation may provide a molecular basis for the biological
      functions of remodelers.

PMID- 17188034
TI  - Relationships between p63 binding, DNA sequence, transcription activity, and
      biological function in human cells.
AB  - Using tiled microarrays covering the entire human genome, we identify
      approximately 5800 target sites for p63, a p53 homolog essential for stratified
      epithelial development. p63 targets are enriched for genes involved in cell
      adhesion, proliferation, death, and signaling pathways. The quality of the
      derived DNA sequence motif for p63 targets correlates with binding strength
      binding in vivo, but only a small minority of motifs in the genome is bound by
      p63. Conversely, many p63 targets have motif scores expected for random genomic
      regions. Thus, p63 binding in vivo is highly selective and often requires
      additional factors beyond the simple protein-DNA interaction. There is a
      significant, but complex, relationship between p63 target sites and p63
      responsive genes, with DeltaNp63 isoforms being linked to transcriptional
      activation. Many p63 binding regions are evolutionarily conserved and/or
      associated with sequence motifs for other transcription factors, suggesting that
      a substantial portion of p63 sites is biologically relevant.

PMID- 17188035
TI  - S. cerevisiae Tel1p and Mre11p are required for normal levels of Est1p and Est2p
      telomere association.
AB  - In diverse organisms, the Mre11 complex and phosphoinositide 3-kinase-related
      kinases (PIKKs), such as Tel1p and Mec1p from S. cerevisiae, are key mediators of
      DNA repair and DNA damage checkpoints that also function at telomeres. Here, we
      use chromatin immunoprecipitation (ChIP) to determine if Mre11p, Tel1p, or Mec1p
      affects telomere maintenance by promoting recruitment of telomerase subunits to
      S. cerevisiae telomeres. We find that recruitment of Est2p, the catalytic subunit
      of telomerase, and Est1p, a telomerase accessory protein, was severely reduced in
      mre11Delta and tel1Delta cells. In contrast, the levels of Est2p and Est1p
      binding in late S/G2 phase, the period in the cell cycle when yeast telomerase
      lengthens telomeres, were indistinguishable in wild-type (WT) and mec1Delta
      cells. These data argue that Mre11p and Tel1p affect telomere length by promoting
      telomerase recruitment to telomeres, whereas Mec1p has only a minor role in
      telomerase recruitment in a TEL1 cell.

PMID- 17188036
TI  - A DEAD protein that activates intron self-splicing without unwinding RNA.
AB  - The group II intron ai5gamma from S. cerevisiae requires high temperature and
      salt to self-splice in vitro, but it is assisted by the protein Mss116 in vivo.
      Here we show that Mss116 can stimulate splicing of ai5gamma under near
      physiological conditions in vitro, which represents one of the first cases in
      which a DExH/D protein is shown to act on its natural target. Importantly, we
      demonstrate that a small subset of DEAD-box proteins can also stimulate ai5gamma
      splicing in vitro and may represent a distinct subfamily of DEAD-box proteins
      that functions in RNA tertiary structure assembly. Mutational analysis shows that
      while ATPase activity is required for stimulation of splicing by Mss116, helicase
      activity is not. This finding indicates that Mss116 is unlikely to promote intron
      splicing through the unwinding of kinetic traps. Rather, we propose that Mss116
      promotes the ordered assembly of large RNA molecules through stabilization of on
      pathway intermediates.

PMID- 17188037
TI  - A late-acting quality control process for mature eukaryotic rRNAs.
AB  - Ribosome biogenesis is a multifaceted process involving a host of trans-acting
      factors mediating numerous chemical reactions, RNA conformational changes, and
      RNA-protein associations. Given this high degree of complexity, tight quality
      control is likely crucial to ensure structural and functional integrity of the
      end products. We demonstrate that ribosomal RNAs (rRNAs) containing individual
      point mutations, in either the 25S peptidyl transferase center or 18S decoding
      site, that adversely affect ribosome function are strongly downregulated in
      Saccharomyces cerevisiae. This downregulation occurs via decreased stability of
      the mature rRNA contained in fully assembled ribosomes and ribosomal subunits.
      Thus, eukaryotes possess a quality-control mechanism, nonfunctional rRNA decay
      (NRD), capable of detecting and eliminating the rRNA component of mature
      ribosomes.

PMID- 17188038
TI  - A chaperone-dependent GSK3beta transitional intermediate mediates activation-loop
      autophosphorylation.
AB  - Glycogen synthase kinase 3 (GSK3), a key component of the insulin and wnt
      signaling pathways, is unusual, as it is constitutively active and is inhibited
      in response to upstream signals. Kinase activity is thought to be increased by
      intramolecular phosphorylation of a tyrosine in the activation loop (Y216 in
      GSK3beta), whose timing and mechanism is undefined. We show that GSK3beta
      autophosphorylates Y216 as a chaperone-dependent transitional intermediate
      possessing intramolecular tyrosine kinase activity and displaying different
      sensitivity to small-molecule inhibitors compared to mature GSK3beta. After
      autophosphorylation, mature GSK3beta is then an intermolecular serine/threonine
      kinase no longer requiring a chaperone. This shows that autoactivating kinases
      have adopted different molecular mechanisms for autophosphorylation; and for
      kinases such as GSK3, inhibitors that affect only the transitional intermediate
      would be missed in conventional drug screens.

PMID- 17188039
TI  - LXIII Edward Jackson Memorial Lecture: Eye care: dollars and sense.
AB  - PURPOSE: The development of health economic data for vision loss and eye disease
      is described. DESIGN: Data from population-based epidemiologic studies of eye
      disease, studies of the impact of vision loss on daily living, Australian
      national health-care costs, census, and demographic projections were combined to
      develop a model of the economic impact of vision loss in Australia. METHODS: Data
      were considered to assess the current magnitude and costs of vision loss and to
      make projections as to future costs. Further analysis investigated the costs and
      economic benefits of various interventions to address avoidable vision loss.
      RESULTS: The amount of vision loss increases three-fold and the number with
      vision loss will double in 20 years. Vision loss cost Australia a total of AU
      $9.85 billion in 2004. Vision loss ranks seventh in causes of loss of well-being.
      An intervention package to address avoidable vision loss would cost AU $190
      million or AU $5,591/Quality Adjusted Life Year (QALY) and give lifetime savings
      of AU $911 million. CONCLUSIONS: Although specific for Australia, these data can
      help guide health care policy debate and the priority given to eye care in other
      developed economies. For each dollar spent on the prevention of vision loss and
      eye care, there is a 5 dollar return to the community.

PMID- 17188040
TI  - A prospective randomized clinical trial of phacoemulsification vs manual
      sutureless small-incision extracapsular cataract surgery in Nepal.
AB  - PURPOSE: To compare the efficacy and visual results of phacoemulsification vs
      manual sutureless small-incision extracapsular cataract surgery (SICS) for the
      treatment of cataracts in Nepal. DESIGN: Prospective, randomized comparison of
      108 consecutive patients with visually significant cataracts. METHODS: settings:
      Outreach microsurgical eye clinic. patients: One hundred eight consecutive
      patients with cataracts were assigned randomly to receive either
      phacoemulsification or SICS. intervention Cataract surgery with implantation of
      intraocular lens. main outcome measures: Operative time, surgical complications,
      uncorrected and best-corrected visual acuity (BCVA), astigmatism, and central
      corneal thickness (CCT). RESULTS: Both surgical techniques achieved excellent
      surgical outcomes with low complication rates. On postoperative day 1, the groups
      had comparable uncorrected visual acuity (UCVA) (P = 0.185) and the SICS group
      had less corneal edema (P = 0.0039). At six months, 89% of the SICS patients had
      UCVA of 20/60 or better and 98% had a best-corrected visual acuity (BCVA) of
      20/60 or better vs 85% of patients with UCVA of 20/60 or better and 98% of
      patients with BCVA of 20/60 or better at six months in the phaco group (P =
      0.30). Surgical time for SICS was much shorter than that for phacoemulsification
      (P < .0001). CONCLUSION: Both phacoemulsification and SICS achieved excellent
      visual outcomes with low complication rates. SICS is significantly faster, less
      expensive, and less technology dependent than phacoemulsification. SICS may be
      the more appropriate surgical procedure for the treatment of advanced cataracts
      in the developing world.

PMID- 17188041
TI  - Changes in corneal biomechanics and intraocular pressure following LASIK using
      static, dynamic, and noncontact tonometry.
AB  - PURPOSE: To compare the preoperative and postoperative measurement of corneal
      biomechanical properties and intraocular pressure (IOP) using Goldmann
      applanation tonometry (GAT), the ocular response analyzer (ORA), and the Pascal
      dynamic contour tonometer (PDCT) in eyes undergoing myopic laser in situ
      keratomileusis (LASIK). DESIGN: Prospective, nonrandomized clinical trial.
      METHODS: IOP was measured in 66 myopic eyes before and after LASIK by GAT, ORA,
      and PDCT in a randomized sequence. Metrics of corneal biomechanical properties
      (corneal hysteresis [CH], corneal resistance factor [CRF], and ocular pulse
      amplitude [OPA]) were recorded. RESULTS: After LASIK, there was a reduction in
      mean corneal pachymetry of 90.2 mum and in IOP measurements with GAT (Delta = 
      1.8 +/- 2.8 mm Hg; P < .01), ORA-Goldmann (Delta = -4.6 +/- 2.8 mm Hg, P < .01),
      and ORA-corneal compensated (Delta - 2.1 +/- 2.6 mm Hg; P < .05). However, there
      was no statistically significant difference between preoperative and
      postoperative IOP measurements taken by PDCT (Delta = -0.5 +/- 2.6 mm Hg).
      Postoperatively, CRF decreased by 28.6% (P < .01), CH by 16.2% (P < .01), and OPA
      by 1.8% (P = .32). CONCLUSIONS: Measurement of IOP with PDCT appears to be
      relatively immune to changes in corneal biomechanics and pachymetry after LASIK,
      in comparison to GAT and ORA measures of IOP. PDCT and ORA both showed
      statistically lower variation in measurement than GAT. LASIK produced a marked
      decline in CH and CRF, which may reflect respective changes in the viscous and
      elastic qualities of the post-LASIK cornea. In contrast, there was no statistical
      change in OPA.

PMID- 17188042
TI  - Photodynamic therapy vs limited macular translocation in the management of
      subfoveal choroidal neovascularization in pathologic myopia: a two-year study.
AB  - PURPOSE: To compare the results of limited macular translocation and photodynamic
      therapy (PDT) in subfoveal choroidal neovascularization (CNV) attributable to
      pathologic myopia with a 24-month follow-up. DESIGN: Retrospective analysis of
      nonrandomized interventional clinical study. METHODS: Retrospective review of 66
      consecutive patients: 34 myopic eyes with subfoveal neovascularization treated by
      PDT and 32 operated on with the translocation technique. Translocation was
      considered principally when the lesion size was adequate (nasal inferior margin
      of the membrane less than half a disk diameter away from the center of the fovea)
      with duration of symptoms of less than four months. Main outcome measure was the
      postoperative change in visual acuity. RESULTS: In the translocation group, mean
      gain in visual acuity was greater than in the PDT group (+2.8 lines and -1.8
      line, respectively, P = .001). In the translocation group, 55% of eyes gained 3
      lines or more at two years compared with 10% in the PDT group. Sixty percent of
      eyes in the translocation group vs 40% in the PDT group had an improvement of at
      least five letters. Mean foveal displacement after translocation was 906 mum;
      postoperative complications included retinal detachment (three eyes), macular
      fold (one eye), and transient diplopia (four eyes). In young patients, the
      postoperative gain was better in both groups. In the translocation group, mean
      survival time for choroidal neovascularization recurrence was 40 months for
      patients younger than 40 years and 20 months for older patients. CONCLUSIONS:
      Translocation showed better results than PDT at two years. Further studies are
      required to confirm these findings.

PMID- 17188043
TI  - Photodynamic therapy for nonsubfoveal choroidal neovascularization in 100 eyes
      with pathologic myopia.
AB  - PURPOSE: To evaluate the visual and anatomic outcome of photodynamic therapy
      (PDT) in eyes with nonsubfoveal choroidal neovascularization (CNV) associated
      with pathologic myopia (PM). DESIGN: Interventional, noncomparative cases series.
      METHODS: Ninety-seven patients (100 eyes) who were treated with PDT at three
      centers and followed up for three to 44 months (mean 16.5 months). Outcome
      measures were visual acuity, lesion size, and the occurrence of subfoveal
      invasion. RESULTS: Median baseline visual acuity was 20/40(-2) and ranged from
      20/20 to 20/160(+2). On average, visual acuity was stable throughout follow-up
      after a modest increase of about 0.5 lines between three and six months. The
      probability of losing 3 or more lines was 10% to 15% during the second year.
      Lesion size (median: 710 microns) slightly decreased after the first PDT and
      tended to increase later, but not to a statistically significant extent compared
      with baseline. The probability of developing subfoveal CNV stabilized at 10% in
      the second year. The mean number of PDTs per individual was 2.9 in the first year
      and 0.6 in the second. CONCLUSIONS: Visual and anatomic outcomes of PDT, in this
      large group of patients with nonsubfoveal myopic CNV and good visual acuity,
      suggest that it may halt the progression of the disease in most cases.

PMID- 17188044
TI  - Progressive visual loss in subfoveal exudation in age-related macular
      degeneration: a meta-analysis using Lineweaver-Burke plots.
AB  - PURPOSE: To analyze the randomized clinical trials in exudative age-related
      macular degeneration (AMD) to reveal apparent differences in the behavior of
      untreated control eyes among these trials. Herein we test the hypothesis that the
      behavior of untreated control eyes is actually the same in all studies, with
      apparent differences arising from differences in the time of entry of eyes into
      clinical trials. DESIGN: Retrospective meta-analysis of prior clinical trials.
      METHODS: Control eye data from six AMD studies (Macular Photocoagulation Study,
      Subfoveal Surgery Trial, Photodynamic Therapy [TAP] With Visudyne, pegaptanib
      trial for neovascular AMD, anecortave acetate trial, and 360 degree Macular
      Translocation Study) were plotted on a double reciprocal plot of 1/(Letters Lost)
      vs 1/(Months After Enrollment). To account for differences in time of entry into
      clinical trials, we introduced a horizontal translation factor to shift each data
      subset horizontally to maximize r(2) for the cumulative trend line. RESULTS:
      Cumulative data for untreated control eyes fits a straight line on a double
      reciprocal plot (r(2) = .9521); an untreated eye would eventually deteriorate to
      a final vision of 20/640. The slope of the line predicts that patients would
      experience half of the maximum final vision within 10.88 months after exudation
      onset. CONCLUSIONS: The pattern of vision loss experienced in AMD eyes with
      subfoveal neovascularization is uniform across a wide range of clinical trials,
      with apparent differences arising from differences in the time of entry of
      patients into clinical trials.

PMID- 17188045
TI  - Clinical outcomes after deep anterior lamellar keratoplasty using the big-bubble
      technique in patients with keratoconus.
AB  - PURPOSE: To report clinical outcomes of deep anterior lamellar keratoplasty
      (DALK) using the big-bubble technique in patients with keratoconus. DESIGN:
      Prospective noncomparative interventional study. METHODS:  SETTING: Single
      hospital. PATIENTS: Eighty-one unselected consecutive patients with moderate to
      advanced keratoconus intolerant to contact lenses and with poor spectacle
      corrected visual acuity. INTERVENTION: DALK big-bubble technique. MAIN OUTCOME
      MEASURES: Intraoperative and postoperative complications, postoperative
      uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      manifest refraction, corneal topography, and endothelial cell density. RESULTS:
      Seventy-eight procedures (96%) were completed as DALK. Big-bubble was achieved in
      50 cases (64%); 28 (36%) required manual intrastromal dissection. Intraoperative
      microperforations occurred in 11 cases (13%). Baseline mean uncorrected visual
      acuity was 20/500 and 20/60 two years after surgery. Average preoperative BSCVA,
      was 20/100 and 20/30 at the end of follow-up. Final BSCVA was better in patients
      in whom big-bubble with exposure of the Descemet membrane was achieved (P < .05).
      Average keratometry and SD (standard deviation) refraction changed from 62.1 +/-
      6.7 diopters and -10.76 +/- 5 diopters to 47.51 +/- 4.73 diopters and -1.81 +/-
      3.2 diopters, respectively after surgery. Mean preoperative endothelial cell
      density was 2202.29 +/- 392.35 cells/mm(2) and 2034 +/- 438.39 cells/mm(2) two
      years after surgery. Two patients developed stromal rejection. CONCLUSIONS: The
      DALK big-bubble technique is a valuable treatment in patients with keratoconus.
      Visual outcome is comparable to standard penetrating keratoplasty (PK) when
      formation of big-bubble with exposure of the Descemet membrane (DM) was achieved.
      Clinically important graft-host interface developed in some cases after manual
      intrastromal dissection. Stromal rejection is a rare complication.

PMID- 17188046
TI  - The OPA1 gene polymorphism is associated with normal tension and high tension
      glaucoma.
AB  - PURPOSE: To assess whether genetic polymorphisms of optic atrophy 1 (OPA1) are
      associated with primary open-angle glaucoma (POAG). DESIGN: Prospective case
      control association study. METHODS: Japanese patients with normal tension
      glaucoma (NTG, n = 194), and high tension glaucoma (HTG, n = 191), and 185
      control subjects were analyzed for the OPA1 intervening sequence (IVS) 8+4
      cystosine thymine (C/T) and IVS 8+32 thymine cystosine (T/C) polymorphisms using
      pyrosequencing technique. RESULTS: There was a significant difference in the OPA1
      IVS 8 +32 T/C genotype frequencies between the NTG patients and control subjects
      (P = .0074), and the frequency of the cystosine (C) allele was significantly
      higher in the NTG patients compared with the control subjects (19.3% vs 11.6%, P
      = .0036). Adjusted for age, gender, refractive error, and intraocular pressure,
      an almost two-fold increased risk of NTG (P = .004, odds ratio 2.27, 95%
      confidence interval 1.30 to 3.97) was found with the OPA1 IVS 8 +32 C allele.
      Although there was no significant difference in the OPA1 IVS 8 +32 T/C genotype
      frequencies between the HTG patients and control subjects (P = .24), the age at
      the time of diagnosis (53 +/- 11.0 years, median value +/- median absolute
      deviation) in the HTG patients with the OPA1 IVS 8 +32 C allele was significantly
      younger than that (57 +/- 12.0 years) in the HTG patients without C allele (P =
      .048). CONCLUSIONS: The OPA1 IVS 8 +32 T/C polymorphism is associated with NTG,
      and may be used as a marker for this disease association. This polymorphism also
      influences the phenotypic feature in patients with HTG and should be considered
      to be a genetic risk factor not only for NTG, but also for HTG.

PMID- 17188047
TI  - Ocular fungal isolates and antifungal susceptibility in northern China.
AB  - PURPOSE: To analyze the distribution characteristics of ocular fungal isolates
      and antifungal susceptibility in vitro. DESIGN: A retrospective case-series
      descriptive study. METHODS: Two thousand one hundred and seventy-nine specimens
      collected from Tongren Hospital during 2001 to 2004 were identified at the
      Beijing Institute of Ophthalmology. Fungal culture-positive rate, antifungal
      susceptibility in vitro, and genus distribution of positive cultures were
      analyzed retrospectively. For the fungal culture-positive samples, the gender and
      age of the patients, the location of ocular involvement, and the season of the
      onset of mycotic ocular diseases were studied. The fungal positive isolates were
      subjected to antifungal susceptibility testing. RESULTS: Out of 2,179 specimens,
      681 specimens were positive cultures. The culture-positive rate was 31.25%. Out
      of 681 specimens of positive cultures, 591 specimens were from the cornea, 29
      from the aqueous humor, 22 from the conjunctiva, 22 from the vitreous body, one
      from the lacrimal sac, and 16 from the other sites. Fusarium species was the most
      common pathogen identified in 394 (57.86% of positive cultures), followed by
      Aspergillus species in 116 (17.03% of positive cultures). Out of 681 positive
      cultures, the sensitivity in vitro to natamycin, terbinafine, itraconazole, and
      fluconazole were 608/681 (89.28%), 467/681 (68.58%), 260/681 (38.18%), and
      101/681 (14.83%), respectively. Three hundred and sixty-eight (93.4%) of Fusarium
      species were sensitive to natamycin, 107 (92.2%) of Aspergillus species were
      sensitive to itraconazole. CONCLUSIONS: Fusarium species was the predominant
      pathogen, which resulted in mycotic ocular diseases in northern China, followed
      by Aspergillus species. Most of the Fusarium species were sensitive to natamycin,
      and most of the Aspergillus species were sensitive to itraconazole.

PMID- 17188048
TI  - Glaucoma tube or trabeculectomy? That is the question.

PMID- 17188049
TI  - Phacoemulsification vs small-incision manual cataract surgery: an expert trial.

PMID- 17188050
TI  - Scientific challenges in postmarketing surveillance of ocular adverse drug
      reactions.
AB  - PURPOSE: To highlight the challenges of postmarketing surveillance for drug
      related adverse events in the practice of ophthalmology. DESIGN: A retrospective
      review of the medical literature and postmarketing surveillance databases.
      METHODS: MEDLINE literature review of sildenafil-associated or amiodarone
      associated optic neuropathy and chloramphenicol-associated blood dyscrasias.
      RESULTS: Sildenafil, amiodarone, and chloramphenicol may all cause adverse ocular
      events; however, the data are not conclusive. CONCLUSIONS: Reports in peer
      reviewed medical journals may be proven incorrect over time. For drug-induced
      adverse ocular events, there is little true science after the drug reaches the
      marketplace, so the percentage of incorrect conclusions may be high. Clinicians
      should be wary of reports of adverse ocular effects until data are confirmed by
      multiple authors over the long-term. Even so, spontaneous reports from
      postmarketing surveillance databases may be the first and only signal of an
      adverse ocular event.

PMID- 17188051
TI  - Incidence of intraoperative floppy iris syndrome in patients on either systemic
      or topical alpha(1)-adrenoceptor antagonist.
AB  - PURPOSE: To evaluate the incidence of Intraoperative Floppy Iris syndrome (IFIS)
      in relation to the usage of alpha(1)-adrenoceptor antagonists. DESIGN:
      Prospective, interventional case series. METHODS: In 2,643 consecutive eyes of
      1,968 patients undergoing cataract surgery, occurrence of IFIS and use of
      alpha(1) antagonists were recorded. RESULTS: IFIS was observed in 29 eyes (1.1%)
      of 25 male patients, all of whom were receiving alpha(1) antagonists. In those
      receiving systemic tamsulosin, alpha(1A) selective antagonist, IFIS developed in
      25 (43.1%) of 58 eyes. In those receiving systemic naftopidil, alpha(1A) and
      alpha(1D) antagonists, IFIS was found in 4 (19.0%) of 21 eyes. There was no case
      of IFIS in patients who received other systemic alpha(1) antagonists and in eyes
      treated with bunazosin eyedrops, a nonselective alpha(1) antagonist. CONCLUSIONS:
      IFIS occurred in 1.1% of cases treated with systemic alpha(1A)-adrenoceptor
      antagonists for benign prostatic hypertrophy. Topical nonselective alpha(1)
      antagonist did not induce IFIS.

PMID- 17188052
TI  - Topical and oral voriconazole in the treatment of fungal keratitis.
AB  - PURPOSE: To describe nine patients with fungal keratitis refractory to standard
      antifungal therapy whose condition was managed with voriconazole. DESIGN:
      Retrospective case series. METHODS: Chart review of patients with fungal
      keratitis who were treated with topical and oral voriconazole. RESULTS: Nine
      patients were treated. Two patients were contact lens wearers who used
      multipurpose cleaning solutions. Corneal isolates found were Fusarium (three
      patients), Candida albicans (three patients), Alternaria (one patient),
      Scopulariopsis (one patient), and Scedosporium apiospermum (one patient). Nine
      patients were treated with topical voriconazole, and eight patients were treated
      with oral voriconazole. Patients were treated topically for four to 16 weeks
      (mean, 10 weeks) and orally for five to 17 weeks (mean, 10 weeks). One patient
      was lost to follow-up. Two patients discontinued the topical voriconazole after
      one day and four weeks, respectively, because of ocular burning. Of the seven
      patients who were treated with topical therapy and followed, five conditions
      healed. CONCLUSION: Voriconazole is a new, promising therapy for fungal keratitis
      that is refractory to standard antifungal treatments.

PMID- 17188053
TI  - Double-mirror goniolens with dual viewing system for goniosurgery.
AB  - PURPOSE: To compare the performance of the double-mirror goniolens with dual
      viewing system in goniosurgery, goniosynechialysis, and trabeculotomy ab externo
      with that of the conventional Swan-Jacob gonioprism (SJG). DESIGN: Prospective
      interventional case series. METHODS: We treated 10 patients (10 eyes) with
      medically uncontrollable chronic angle-closure glaucoma by goniosynechialysis and
      another 10 eyes with open-angle glaucoma by trabeculotomy ab externo (TLO). The
      20 patients were divided randomly into two equal groups and underwent operation
      with the double-mirror goniolens or SJG instrument. RESULTS: There were no
      intraoperative complications, irrespective of the procedure or instrument that
      was used. Patients in the SJG group were required to tilt the head at a >30
      degree angle to facilitate observation and manipulation of the quadrants. On the
      other hand, all structures could be observed and manipulated without head-tilting
      in the double-mirror goniolens group. CONCLUSION: The double-mirror goniolens
      with dual viewing system is more suitable than the conventional SJG for
      goniosurgery.

PMID- 17188054
TI  - Intraoperative sclerotomy-related retinal breaks for macular surgery, 20- vs 25
      gauge vitrectomy systems.
AB  - PURPOSE: To compare the rate of intraoperative sclerotomy-related retinal breaks
      (SRRB) between 20- and 25-gauge vitrectomy systems for the correction of macular
      pucker (MP) and macular hole (MH). DESIGN: Retrospective interventional case
      series. METHODS: Single institution review of 347 consecutive eyes of 333
      patients between August 2003 and May 2005 receiving pars plana vitrectomy (PPV)
      for MP or MH repair. Eyes were excluded if they had any form of proliferative
      retinopathy, or if there was an intraoperative conversion of any sclerotomy from
      25- to 20- gauge. RESULTS: Fourteen (6.4%) of 219 eyes in the 20-gauge group had
      SRRB vs 4 (3.1%) of 128 eyes in the 25-gauge group (Fisher exact test, P value =
      .22). CONCLUSIONS: There was a trend for slightly lower rates of intraoperative
      sclerotomy-related retinal breaks, single or multiple, with 25-gauge PPV compared
      with 20-gauge PPV, but the differences were not statistically significant.

PMID- 17188055
TI  - Is early age-related macular degeneration associated with cerebral MRI changes?
      The Atherosclerosis Risk in Communities study.
AB  - PURPOSE: To examine the relation of early age-related macular degeneration (AMD)
      with cerebral magnetic resonance imaging (MRI) changes. DESIGN: Population-based,
      cross-sectional study. METHODS: A sample of 1,684 persons ages 51 to 72 years
      with no history of stroke had cerebral MRI and retinal photography. MRI scans
      were graded for severity of white matter lesions (WML), sulcal widening (SW), and
      ventricular enlargement (VE). AMD was graded from retinal photographs. RESULTS:
      After adjustment for age, gender, race, or center, early AMD (5.0% of
      participants) was not significantly associated with WML (odds ratio [OR] 1.0, 95%
      confidence intervals [CI], 0.6 to 1.6), SW (OR 0.6, 95% CI, 0.4 to 1.2), or VE
      (OR 1.0, 95% CI, 0.6 to 1.8). CONCLUSIONS: These data showed no statistically
      significant association of early AMD with cerebral MRI changes, but the study was
      limited by a small number of cases with wide CIs. Further studies may clarify
      these associations.

PMID- 17188056
TI  - Central corneal thickness and visual field loss in fellow eyes of patients with
      open-angle glaucoma.
AB  - PURPOSE: To determine the relationship of central corneal thickness (CCT) and
      visual field loss between fellow eyes in primary open-angle glaucoma. DESIGN:
      Retrospective, observational case series. METHODS: Records review of glaucoma
      patients seen at local Veterans Administration eye clinic. Those with CCT
      measurements performed within one month of visual field testing were included.
      Patients were excluded with vision below 20/40 or disease that would affect
      visual fields. Intrasubject (between fellow eyes) differences in CCT, mean
      deviation (MD), and pattern standard deviation (PSD) were calculated by
      subtracting left eye value from right eye value. RESULTS: Of the 100 subjects (94
      males), the Spearman correlation coefficient between intrasubject differences in
      CCT vs intrasubject differences in MD was 0.36 (P = .0003). The Spearman
      correlation for differences in CCT vs differences in PSD was -0.31 (P = .0019).
      CONCLUSIONS: Our study suggests that worse visual field changes tend to occur in
      the eye with the thinner cornea.

PMID- 17188057
TI  - Giant cell arteritis among Hispanic Americans.
AB  - PURPOSE: To compare the prevalence and clinical course of giant cell arteritis
      (GCA) among Hispanic and non-Hispanic patients. DESIGN: Comparative case series.
      METHODS: Two hundred fifty-seven consecutive patients who underwent temporal
      artery biopsy in our institution from 1996 to 2002 were studied. A prospective
      telephone survey was conducted to determine race and Hispanic origin separately
      by means of methodology of the US Census Bureau. RESULTS: One hundred thirty-four
      patients completed the interview, with 65 (49%) identifying themselves as
      Hispanic and 69 (51%) as non-Hispanic. Of the 32 respondents with biopsy-proven
      GCA, all identified themselves racially as white, and 13 (41%) were Hispanic and
      19 (59%) were non-Hispanic (P = .32). Statistically significant differences in
      age, presenting symptoms, and final visual acuity were not observed among
      Hispanic and non-Hispanic patients with GCA. CONCLUSIONS: Although GCA has been
      reported to be rare in Hispanics, we found the prevalence and clinical course of
      GCA to be similar in Hispanic and non-Hispanic patients.

PMID- 17188058
TI  - Optical coherence tomography findings in acute retinal pigment epitheliitis.
AB  - PURPOSE: To report the optical coherence tomography (OCT) findings in three
      patients with acute retinal pigment epitheliitis (ARPE). DESIGN: Retrospective,
      observational case series. METHODS: The charts of three patients with ARPE were
      reviewed. Approval from the Institutional Review Board was obtained. Fundus
      photographs, fluorescein angiograms, and OCT findings were examined. RESULTS:
      Three healthy, young patients presented with acute unilateral blurred vision.
      Ophthalmoscopy revealed fine pigment stippling surrounded by haloes of
      hypopigmentation. Fluorescein angiography demonstrated transmission
      hyperfluorescence. OCT showed abnormal foveal hyperreflectivity involving the
      outer nuclear layer and photoreceptors in all cases. Disruption of the retinal
      pigment epithelium (RPE) was seen in two cases. With resolution, the abnormal
      hyperreflectivity decreased in thickness. CONCLUSIONS: OCT confirms the
      involvement of the outer neurosensory retina in acute retinal pigment
      epitheliitis. RPE involvement may be a secondary post-inflammatory response,
      because one case did not have significant disruption of the RPE.

PMID- 17188059
TI  - Self-retaining 27-gauge transconjunctival chandelier endoillumination for
      panoramic viewing during vitreous surgery.
AB  - PURPOSE: To report the development of a 27-gauge self-retaining transconjunctival
      chandelier endoilluminator for panoramic viewing during vitrectomy. DESIGN: New
      surgical instrument. METHODS: The tip of the illuminating fiber is 27-gauge (0.35
      mm) and shaped like a cone to provide wide-angle illumination. The tip, inserted
      approximately 3 mm into the vitreous cavity transconjunctivally, provides diffuse
      illumination. The optical fiber covered by a malleable sleeve can be retained in
      the eyeball without a suture. RESULTS: The slim light fiber design (0.35 mm)
      stabilizes the 27-gauge tip in the eye and provides up to 25 lumens of measured
      illumination. The adequate lighting potential and self-retaining design allow
      wide-angle visualization and bimanual manipulation in challenging cases. Easy
      insertion and removal without suture placement make it convenient to change the
      position of the device during surgery and efficiently shorten surgical time.
      CONCLUSIONS: This suture-free 27-gauge endoillumination chandelier improves the
      efficacy and efficiency of vitreous surgery.

PMID- 17188060
TI  - Thermal injury caused by chandelier fiber probe.
AB  - PURPOSE: To investigate thermal changes produced by a chandelier fiber probe
      (CFP). DESIGN: Interventional single case report and laboratory investigation.
      METHODS: When CFP was used for 25-gauge vitrectomy, an abnormal odor was emitted,
      and the CFP was instantly removed. To investigate this incident, the thermal
      change produced by the CFP was measured in air by means of an infrared sensor.
      Porcine Tenon capsular tissue was used to reproduce the intraoperative
      phenomenon. RESULTS: In our patient, the CFP tip melted, but this did not affect
      visual function. In the experiment, the uncoated CFP reached 49 C (120 F) at
      maximum illumination. When porcine Tenon capsular tissue was attached to the CFP
      tip, a temperature of 144 C (291 F) was reached at 50% of maximum illumination,
      and over 201 C (394 F) at 75%. The tip melted under these conditions.
      CONCLUSIONS: At present, we avoid the use of CFP during air exchange. This
      potential hazard of the CFP needs to be addressed.

PMID- 17188061
TI  - Visual hallucinations after intravitreal injection of bevacizumab in vascular age
      related macular degeneration.
AB  - PURPOSE: To describe transient structured visual hallucinations in a patient with
      vascular age-related macular degeneration (AMD), following an intravitreal
      Avastin-injection. DESIGN: Interventional case reports. METHODS: A fully alert 83
      year-old woman with disciform scar right eye (OD) and occult choroidal
      neovascularization (CNV) left eye (OS) experienced a progressive visual loss to
      20/800 OD and 20/400 OS. A coherent 84-year-old woman with occult CNV both eyes
      (OU) experienced decreased vision of 20/800 OU. After both patients gave informed
      consent, an uneventful intravitreal injection of 1.25 mg Avastin was performed in
      the left eyes. RESULTS: One day and three days after an uneventful intravitreal
      injection both patients experienced structured hallucinations including trees,
      faces, and water for approximately 15 to 30 minutes. CONCLUSIONS: We report a
      typical symptoms of Charles-Bonnet syndrome (CBS) in patients with severe AMD
      after intravitreal Avastin-injections. The reduced retinal edema and realignment
      of the photoreceptors may promote the release phenomenon and trigger
      hallucinatory episodes.

PMID- 17188062
TI  - Photoreceptor status after resolved macular edema in branch retinal vein
      occlusion treated with tissue plasminogen activator.
AB  - PURPOSE: To evaluate the integrity of photoreceptors in macular edema (ME)
      associated with branch retinal vein occlusion after intravitreal tissue
      plasminogen activator. DESIGN: Retrospective, interventional case series.
      METHODS: Nineteen eyes with ME by branch retinal vein occlusion were treated with
      intravitreal tissue plasminogen activator injection. We assessed visual acuity
      (VA) and the presence or absence in the fovea of a third high reflectance band
      (HRB) by optical coherence tomography at the final visit. RESULTS: No differences
      were found in age, preoperative VA, and foveal thickness between the groups with
      or without the third HRB. After treatment, the mean VA improved significantly (P
      < .05) in both groups. At the final visit, the mean VA in the group without HRB
      was significantly poorer than the group with HRB (P = .0042); foveal thickness
      did not differ between the groups. CONCLUSIONS: The integrity of the third HRB in
      the fovea is associated with VA after the resolution of ME.

PMID- 17188064
TI  - Vitreous levels of interleukin-8 in patients with proliferative diabetic
      retinopathy.
AB  - PURPOSE: To determine the levels of interleukin 8 (IL-8) in the vitreous of
      patients with proliferative diabetic retinopathy (PDR). DESIGN: Observational
      case-control study. METHODS: Vitreous fluid samples were obtained by
      vitreoretinal surgery from 71 eyes of patients with diabetes mellitus type 2 with
      PDR and from 17 eyes of nondiabetic patients with a macular hole. PDR was
      classified as active and inactive and subdivided according to the extent of large
      vessel gliotic obliteration. The cytokine levels were measured by cytometric bead
      array method. RESULTS: The vitreous levels of IL-8 were significantly higher in
      patients with PDR in comparison with the control subjects (P < .001) and in
      patients with higher extent of large vessel gliotic obliteration (P < .001). A
      vitreous level of IL-8 was not associated with the presence of active PDR.
      CONCLUSION: Increased levels of IL-8 in PDR were associated with a higher extent
      of large-vessel gliotic obliteration.

PMID- 17188063
TI  - Dronabinol and retinal hemodynamics in humans.
AB  - PURPOSE: To investigate the effects of oral cannabinoids on retinal hemodynamics
      assessed by video fluorescein angiography in healthy subjects. DESIGN:
      Interventional study. METHODS: In a self-experiment, the cannabinoid dronabinol
      (delta-9-tetrahydrocannabinol [THC]) was administered orally to eight healthy
      medical doctors (7.5 mg Marinol; Unimed Pharmaceuticals, Chicago, Illinois, USA).
      At baseline and two hours after dronabinol intake, intraocular pressure (IOP) was
      measured and retinal hemodynamics were assessed by fluorescein angiography. The
      retinal arteriovenous passage time was determined on the basis of dye dilution
      curves by means of digital image analysis in a masked fashion. RESULTS:
      Dronabinol resulted in a significant IOP reduction from 13.2 +/- 1.9 mm Hg to
      11.8 +/- 2.0 mm Hg (P = .038). The retinal arteriovenous passage time decreased
      from 1.77 +/- 0.35 seconds to 1.57 +/- 0.31 seconds (P = .028). Systemic blood
      pressure and heart rate were not statistically significantly altered.
      CONCLUSIONS: Cannabinoids, already known for their ability to reduce IOP, may
      result in increased retinal hemodynamics. This may be beneficial in ocular
      circulatory disorders, including glaucoma.

PMID- 17188065
TI  - Intravitreal prednisolone sodium succinate reduces diabetic macular edema without
      intraocular pressure rise.
AB  - PURPOSE: To evaluate the six-month results of patients treated with intravitreal
      prednisolone sodium succinate injections for persistent diabetic macular edema.
      DESIGN: Retrospective, noncontrolled, clinical case series. METHODS: Nineteen
      eyes had intravitreal injections with prednisolone sodium succinate. Need for
      retreatment was based on fluorescein angiographic or optical coherence tomography
      evidence of persisting macular edema. RESULTS: Mean visual acuity at six weeks,
      three months, and six months after injection was significantly better than the
      mean preoperative visual acuity (P = .015, P = .004, and P = .031, respectively).
      In none of the studied eyes intraocular pressure exceeded 22 mm Hg. No other
      adverse events, such as endophthalmitis or retinal detachment, occurred.
      CONCLUSIONS: In this small pilot study, mean visual acuity improvement was
      statistically significant up to six months postoperatively. Current results
      suggest that intravitreal injection of the solution of prednisolone sodium
      succinate may be a safe and good alternative in eyes with macular edema.

PMID- 17188066
TI  - A comparison between cultivated and conventional limbal stem cell transplantation
      for Stevens-Johnson syndrome.
AB  - PURPOSE: To compare the resolution of inflammation and long-term results of
      cultivated and conventional limbal stem cell transplantation (LSCT) in a patient
      with Stevens-Johnson syndrome (SJS). DESIGN: Interventional case report. METHODS:
      A 32-year-old man with SJS and bilateral total limbal stem cell deficiency
      underwent cultivated LSCT in the right eye, followed by conventional LSCT in the
      left eye three weeks later. The postoperative medication included dexamethasone
      0.1% and ofloxacin 0.3% eyedrops and a tapering dose of systemic corticosteroid,
      cyclosporine, and cyclophosphamide. Tear samples were collected and analyzed for
      interleukin (IL) 8 levels. RESULTS: Complete corneal epithelialization was
      achieved 48 hours after cultivated LSCT, compared with three weeks after
      conventional LSCT. Ocular inflammation and IL-8 levels decreased more rapidly in
      the eye with cultivated LSCT. Four years after surgery, more severe corneal
      scarring and opacification were noted in the conventional LSCT eye. CONCLUSIONS:
      Cultivated LSCT resulted in a better clinical result and vision, with less
      stromal scarring compared with conventional LSCT.

PMID- 17188067
TI  - Aspergillus fumigatus colonization of punctal plugs.
AB  - PURPOSE: Punctal plugs are used in patients with dry eye syndrome to preserve the
      tears. In this report, I present two cases of Aspergillus fumigatus colonization
      of punctal plugs. DESIGN: Observational series of two cases. METHODS: Approval
      was obtained from the institutional review board. Two men aged 29 and 31 years
      developed black spots inside the hole of punctal plug, which looked like eyeliner
      deposits. The deposits inside the hole of the plug in each patient were removed
      and cultured. RESULTS: Cultures of the two punctal plugs black deposits grew A
      fumigatus. Bacterial cultures were negative. CONCLUSIONS: Colonization of the
      punctal plug hole with A fumigatus was observed in two cases. It is recommended
      that punctal plugs be removed in patients undergoing refractive or intraocular
      procedures or in patients who are receiving topical corticosteroids. Current
      punctal plugs should be redesigned to avoid the presence of an inserter hole.

PMID- 17188069
TI  - Bilateral macular lesions in a 10-year-old girl.
AB  - PURPOSE: To report a previously undescribed macular dystrophy. DESIGN: Single
      descriptive case report. METHODS: Presentation of clinical findings, including
      ophthalmoscopy, fluorescein angiography, full-field and multifocal
      electroretinography (ERG), optical coherence tomography (OCT), and visual fields.
      RESULTS: A 10 year-old Caucasian girl had peculiar reddish blotchy macular
      lesions bilaterally, associated with decreased visual acuity, and no family
      history of similar lesions. Fluorescein angiography was inconclusive and showed
      mottled hyperfluorescence in the macula. The full-field electroretinogram was
      normal, but multifocal ERG revealed diminished waveforms centrally. CONCLUSION:
      This is possibly a new macular dystrophy, the nature of which remains to be
      determined.

PMID- 17188068
TI  - Rapid species determination of Nocardia keratitis using pyrosequencing
      technology.
AB  - PURPOSE: To describe a new technique, pyrosequencing, which allows for the rapid
      identification of Mycobacterium and Nocardia species. DESIGN: Interventional case
      report. METHODS: The medical records of a patient presenting with an infectious
      keratitis were reviewed. RESULTS: A case of Nocardia
      abscessus/arthrititis/asiatica keratitis was diagnosed in a young individual with
      the aid of pyrosequencing technology. Based on presumed antibiotic sensitivities,
      therapy with topical trimethoprim-sulfamethoxazole eyedrops was initiated, and
      the infection was cleared rapidly with minimal residual scarring. CONCLUSIONS:
      Pyrosequencing may be a useful tool in aiding the rapid diagnosis and treatment
      of ocular infections caused by slow-growing pathogens.

PMID- 17188070
TI  - A novel OPA1 mutation responsible for autosomal dominant optic atrophy with high
      frequency hearing loss in a Chinese family.
AB  - PURPOSE: To investigate the genetic findings and phenotypic characters of
      autosomal dominant optic atrophy (ADOA). DESIGN: Case report and experimental
      study. METHODS: Molecular genetic analysis and clinical examinations were
      performed in a Chinese family with ADOA. Mutations in OPA1 were detected by
      direct sequencing. Haplotypes were constructed and compared with the phenotypes
      in the family. RESULTS: Nine family members were diagnosed with ADOA and some of
      them were accompanied with hearing loss and/or high myopia. A novel heterozygous
      mutation, c.2848_2849delGA(p.Asp950CysfsX4), was detected in all ADOA patients.
      The mutation and the mutation bearing haplotype cosegregated with the nine
      affected members. One family member had high myopia without vision or hearing
      loss. This patient along with unaffected ones did not harbor the mutation.
      CONCLUSIONS: A novel mutation, c.2848_2849delGA in OPA1, was identified in a
      Chinese family with ADOA. This mutation is associated with hearing loss, but
      likely not high myopia.

PMID- 17188072
TI  - Midterm results on ocular surface reconstruction using cultivated autologous oral
      mucosal epithelial transplantation.

PMID- 17188073
TI  - Retinal nerve fiber layer thickness in amblyopic eyes.

PMID- 17188074
TI  - Management of patients with ocular hypertension: a cost-effectiveness approach
      from the Ocular Hypertension Treatment Study.

PMID- 17188077
TI  - Effects of collagen nerve guide on neuroma formation and neuropathic pain in a
      rat model.
AB  - BACKGROUND: Posttraumatic neuroma formation is a major cause of neuropathic pain
      that can occur after elective surgery, amputation, or trauma. This study examined
      the use of biosynthetic collagen nerve guides to prevent the development of
      posttraumatic neuromas. METHODS: Collagen nerve guides were applied after
      neurectomy in a rat sciatic nerve model in an effort to stimulate linear neuronal
      outgrowth and reduce random axon sprouting. Animals were monitored for evidence
      of neuropathic pain--autotomy scores were recorded for 8 weeks posttransection-
      after which proximal stumps were excised and processed for histologic analyses.
      RESULTS: Moderate to severe autotomy was observed in 88% (7 of 8) of the control
      (neurectomy) animals. In contrast, 13% (1 of 8) of animals receiving collagen
      nerve guides developed autotomy, which was significantly less than controls (P <
      .01). Qualitative analyses of neurofilament and Schwann cell-labeled nerve
      sections showed a significant enhancement in Schwann cell migration away from the
      proximal stump and advanced linear axonal regrowth in the collagen nerve guide
      treated animals. CONCLUSIONS: Collagen nerve guides alter the regrowth of
      transected nerves and reduce the severity of symptoms associated with neuropathic
      pain.

PMID- 17188078
TI  - Relationship between right portal and biliary systems based on reclassification
      of the liver.
AB  - BACKGROUND: Although the anatomy of the right portal and biliary systems and
      their interrelationships must be understood to safely and satisfactorily perform
      left-sided resection of hilar cholangiocarcinoma or right-lobe living donor liver
      transplantation, the anatomies of the right portal and biliary systems are
      extremely difficult to understand. METHODS: A total of 60 patients with normal
      liver underwent computed tomography during both portography and cholangiography
      to evaluate relationships between the right biliary and portal systems based on
      reclassification of the liver to divide the right liver into 3 segments. RESULTS:
      All ventral and posterior ducts constantly join medially to the anterior portal
      trunk. In contrast, some dorsal ducts join the ventral duct medially and others
      join the posterior duct lateral to the anterior trunk. CONCLUSIONS:
      Reclassification of the liver to divide the right liver into 3 segments
      facilitates an understanding of relationships between the right portal and
      biliary systems.

PMID- 17188079
TI  - Liver resection for benign liver tumors: indications and outcome.
AB  - BACKGROUND: The indications for intervention in cases of benign liver tumors
      include symptoms, suspicion of malignancy, or risk of malignant change. METHODS:
      Eighty-four liver resections for benign tumors were performed in our hospital
      from June 1996 to December 2004. The patient records were reviewed
      retrospectively. RESULTS: The study group (41 females, 43 males; average age,
      41.4 +/- 10.5 y) included 46 cavernous hemangiomas, 27 focal nodular
      hyperplasias, 5 hepatic adenomas, and 6 liver cysts. The indications for
      resection were inability to rule out malignancy (50 [59.5%]), symptoms (33
      [39.3%]), and others (1 [1.2%]). Postoperatively, 28 of the 33 patients had
      resolution of symptoms. Twenty-nine patients (34.5%) had chronic hepatitis B
      infection. CONCLUSIONS: Liver resection for benign liver tumor is safe, but
      indications for intervention must be evaluated carefully. The presence of chronic
      parenchymal liver disease does not increase morbidity in these patients.

PMID- 17188080
TI  - Standard D2 versus extended D2 (D2+) lymphadenectomy for gastric cancer: an
      interim safety analysis of a multicenter, randomized, clinical trial.
AB  - BACKGROUND: A multicenter, randomized, clinical trial was initiated to evaluate
      the possible benefits of extended D2 (D2+) lymphadenectomy after potentially
      curative resection of gastric cancer. METHODS: Standard D2 lymphadenectomy was
      defined according to the Japanese Gastric Cancer Association classification. D2+
      lymph node dissection additionally included the removal of para-aortic nodes.
      RESULTS: Of 781 patients screened, 275 were randomized to standard D2 (n = 141)
      or extended D2+ (n = 134) lymphadenectomy. The overall morbidity rates were
      comparable in D2 (27.7%; 95% confidence interval [CI], 20.3-35.1) and D2+ (21.6%;
      95% CI, 13.7-29.5) groups (P = .248). Pre-existing cardiac disease, splenectomy,
      and excessive blood loss were identified as risk factors for overall and
      nonsurgical complications. Postoperative mortality rates were 4.9% (95% CI, 1.4
      8.5) and 2.2% (95% CI, 0-4.7), respectively (P = .376). CONCLUSIONS: The interim
      safety analysis failed to show any significant difference with regard to the
      extent of lymph node dissection. The surgical outcome was not different between
      the 2 surgeries.

PMID- 17188081
TI  - Role of axillary ultrasound examination in the selection of breast cancer
      patients for sentinel node biopsy.
AB  - BACKGROUND: Sentinel node biopsy (SNB) is a time-consuming procedure that can be
      avoided in presence of axillary metastases. The aim of this study was to assess
      the accuracy of ultrasound scan (US) in the prediction of axillary nodes status
      in patients scheduled for SNB. METHODS: Axillary US was performed and when
      feasible, a core biopsy of suspicious nodes was taken. The nodal status as
      assessed by US and/or core biopsy was compared with final histology. RESULTS: Of
      the 132 patients enrolled, 31 (23.5%) had suspicious axillary nodes according to
      US; 19 (61.3%) were true positive, whereas 12 cases (38.7%) were not. In 14 of 31
      suspicious cases an US-guided core-biopsy was taken, which in 11 of 14 cases
      (78.5%) confirmed the neoplastic involvement. Overall, core biopsy of the nodes
      correctly predicted the final histology in 13 of 14 cases (92.8%). CONCLUSIONS:
      The US of axillary nodes, possibly associated with core biopsy, improved the
      preoperative evaluation of breast cancer patients scheduled for SNB.

PMID- 17188082
TI  - Total splenic vein thrombosis after laparoscopic splenectomy: a possible
      candidate for treatment.
AB  - BACKGROUND: Portal or splenic vein thrombosis (PSVT) is a common disorder after
      laparoscopic splenectomy (LS). Splenomegaly is a well-known risk factor for PSVT.
      However, no treatment strategy for PSVT has been established. METHODS: Thirty
      three consecutive patients who had undergone LS and postoperative imaging
      surveillance were examined. PSVT was classified according to the site of
      thrombosis. We evaluated patient background, operative factors, and clinical
      symptoms. RESULTS: Spleen weight of patients with PSVT (n = 17, median 218 g) was
      greater than that of patients without PSVT (n = 16, median 101 g). Seven patients
      developed thrombosis involving the entire splenic vein (total splenic vein
      thrombosis), and 4 of them had clinical symptoms (fever >38 degrees C and/or
      abdominal pain). The incidence of clinical symptoms was significantly more
      frequent in patients with than without total SVT. Operation time, blood loss, and
      spleen weight were also significantly greater in patients with total SVT.
      Multiple logistic regression analysis demonstrated spleen weight was the
      strongest predictor of PSVT and total SVT. CONCLUSION: Patients with total SVT
      have greater risk factors for PSVT and frequently have clinical symptoms. They
      are candidates for anticoagulation therapy.

PMID- 17188083
TI  - Long-term functional results after laparoscopic surgery for esophageal achalasia.
AB  - BACKGROUND: Evidence on the long-term outcome of laparoscopic Heller-Dor surgery
      is limited. The aim of this study was to assess the long-term outcome of
      achalasic patients after surgery, particularly in relation to the radiologic
      preoperative stage of the disease. METHODS: Sixty-eight patients with achalasia
      were assessed clinically and by esophageal radiology, manometry, and 24-hour
      ambulatory esophageal pH monitoring before and at 3 months, 1, 1 to 3, 3 to 5,
      and 5 to 8 years after a laparoscopic Heller-Dor procedure. RESULTS: At 1 year
      after surgery the symptom score was significantly lower than the preoperative
      score (P < .001), and a satisfactory clinical outcome was seen in more than 90%
      of the patients with stage I, II, and III disease at the preoperative radiologic
      assessment. Only 50% of stage IV patients reported satisfactory results. An
      adequate opening of the lower esophageal sphincter (LES) and LES resting pressure
      of less than 8 mm Hg was achieved in all patients, and esophageal emptying was
      accelerated significantly (P < .001). At the consecutive follow-up evaluation (1
      8 y), a satisfactory outcome was maintained in all stage I, II, and III
      responders. Stage IV patients with initially unsatisfactory results reported a
      worsening of symptoms (P < .02). Patients with pseudodiverticulum had a higher
      symptom score (P < .01). LES opening and resting pressure remained at levels of
      the 1-year follow-up evaluation. Esophageal emptying remained satisfactory in
      stage I, II, and III responders, but deteriorated in stage IV nonresponders and
      in 6 of the 10 patients with a pseudodiverticulum. CONCLUSIONS: A satisfactory
      outcome of the laparoscopic Heller-Dor procedure in stage I, II, and III
      achalasic patients seems to last. Stage IV nonresponders tend to deteriorate over
      time. The development of pseudodiverticulum is associated with an increased
      symptom score.

PMID- 17188084
TI  - African Americans' participation in clinical research: importance, barriers, and
      solutions.
AB  - Ethical and scientifically sound research requires that any sample population
      represent the population as a whole. African-Americans suffer disproportionately
      from cancer, hypertension, and heart failure compared with whites, but they are
      commonly underrepresented in clinical trials of these diseases. Failure to
      include African-American subjects in clinical trials prevents generalizability of
      the results to this population. African-Americans are often underrepresented in
      clinical research for numerous historic, societal, educational, and economic
      reasons. Efforts to improve enrollment of African-American subjects requires
      recognition of the problem, planning, educational efforts, and investigator
      training. The incidence of heart disease and prostate cancer in African-Americans
      dictates that these patients be targeted for clinical trials of surgical
      research. The research team must appreciate the importance of community
      involvement and support in recruiting African-Americans participants.
      Additionally, the continued effort to recruit and train African-American
      investigators must be a priority.

PMID- 17188086
TI  - Appendectomy for appendicitis in patients with schizophrenia.
AB  - BACKGROUND: Anecdotal evidence suggests that schizophrenia patients who require
      surgery have a high rate of adverse outcomes. We searched the Department of
      Veterans Affairs national datasets to determine the clinical course of
      schizophrenia patients with appendicitis who underwent appendectomy. METHODS: The
      Patient Treatment File (the nationwide inpatient database for the Department of
      Veterans Affairs) and the Beneficiary Identification and Records Location System
      were searched to identify all patients with International Classification of
      Diseases, Ninth Revision, Clinical Modification diagnostic codes for
      schizophrenia or schizoaffective disorder diagnosed with appendicitis during
      fiscal years 1995 to 1999. Computer-based information was supplemented with chart
      based data. We sought data on six common preoperative risk factors and 25
      specific adverse outcomes, including death. RESULTS: There were 55 patients
      identified. The mean age was 49, and 96% were men. The median time from symptom
      onset to diagnosis of appendicitis was 3 days. A history of substance abuse was
      obtained in 16 (29%). Disruptive behavior was documented in 16 (29%). Restraints
      were used in 9 (9%). The appendix was perforated in 36 (66%) and gangrenous in 9
      (16%). Thirty-one (56%) had > or = 1 complication; there were 2 in-hospital
      deaths (4%). CONCLUSIONS: This is the first report on this topic in the medical
      literature. Appendicitis is typically diagnosed late in schizophrenic patients.
      Adverse patient behaviors are frequent. The complication and death rates are
      high.

PMID- 17188087
TI  - Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic
      neuropathic ulcers: a phase 1/2 clinical study.
AB  - BACKGROUND: Talactoferrin alfa, a recombinant form of human lactoferrin, is a
      novel immunomodulatory protein with demonstrated ulcer healing properties in
      animal models. METHODS: A phase 1/2 clinical study was conducted at 7 clinical
      sites to determine if talactoferrin can improve wound healing in diabetic
      patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot
      ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each
      received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a
      sequential design, to their ulcer for 30 days. No drug-related adverse events
      were found at any dose level. Phase 2 was a randomized, placebo-controlled,
      single-blind study of 2.5% and 8.5% gels, with patients equally divided between
      the 3 groups. In combination with good wound care, treatment was administered
      topically twice daily to the ulcers for 12 weeks. The primary endpoint was the
      incidence of > or = 75% healing (relative to baseline size). RESULTS: The study,
      which in phase 2 was powered to detect a difference between the placebo and
      combined talactoferrin arms with P < .1, met the primary objective. The groups
      receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of >
      or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%,
      53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2
      active groups when compared with the placebo group showed a strong trend toward
      statistical significance (P = .09). There were no talactoferrin-related adverse
      events or laboratory abnormalities. CONCLUSIONS: Topical talactoferrin appears to
      be safe and well tolerated and improves healing of diabetic neuropathic ulcers.

PMID- 17188088
TI  - Human immunodeficiency virus and hepatitis testing and prevalence among surgical
      patients in an urban university hospital.
AB  - BACKGROUND: Human immunodeficiency virus (HIV), hepatitis B, and hepatitis C
      represent significant public health problems in an urban community. Early
      diagnosis and treatment of these infections can improve survival and allow for
      preventive strategies to reduce further transmission within a community. The aim
      of this study was to evaluate the surgical setting as a potential opportunity for
      early diagnosis of HIV, hepatitis B, and hepatitis C among trauma and non-trauma
      patients. METHODS: We performed a retrospective review of patients presenting for
      surgery over a 10-year period (July 1994 to July 2004) in an urban, university
      based general surgical practice that includes all trauma services, as well as
      emergency department, inpatient, and outpatient surgical consultations. Data
      collected included diagnosis, operation, age, race, history of intravenous drug
      abuse, and HIV, hepatitis B, and hepatitis C test results. RESULTS: Among 2876
      patients presenting for surgery, testing for blood-borne pathogens was less
      likely among trauma patients (21%, 79/380) compared to non-trauma patients (47%,
      1183/2496) (P < .001). Among patients tested, the incidence of blood-borne
      pathogens was similar in the two groups: HIV (26% trauma vs 24% non-trauma, not
      significant [NS]), hepatitis B (4% trauma vs 3% non-trauma, NS), hepatitis C (33%
      trauma vs 41% non-trauma, NS), and co-infection with HIV and hepatitis C (18%
      trauma vs 12% non-trauma, NS). In both groups, blood-borne pathogens were
      associated with intravenous drug abuse (P < .01). CONCLUSION: HIV, hepatitis B,
      and hepatitis C are common in an urban community among both trauma and non-trauma
      surgical patients, although testing is less common among trauma patients. Testing
      of patients during a surgical admission may represent an excellent opportunity
      for early disease-specific services and preventive interventions.

PMID- 17188089
TI  - Young and middle-age associated differences in cytokeratin expression after bone
      fracture, tissue trauma, and hemorrhage.
AB  - BACKGROUND: This study examined whether there is any difference in the lung
      cytokine and cytokeratin 19 levels between young and middle-aged mice after bone
      fracture and soft-tissue trauma hemorrhage (Fx-TH). METHODS: Young (6-8 weeks)
      and middle-aged (12 months) C3H/HeN male mice were subjected to right lower leg
      fracture, trauma hemorrhage (mean arterial blood pressure to 35 +/- 5 mm Hg for
      90 minutes), and resuscitation. RESULTS: The tumor necrosis factor alpha level in
      the lung increased significantly at 2 hours after Fx-TH in both young and middle
      aged mice, whereas at 24 hours the levels remained significantly higher in middle
      aged mice. Interleukin-6 levels increased significantly 24 hours after Fx-TH in
      both groups, whereas interleukin-10 levels increased only in middle-aged mice at
      24 hours under those conditions. Monocyte chemoattractant protein-1 levels
      increased significantly 2 hours after Fx-TH. The protein and messenger RNA levels
      of cytokeratin 19 were significantly higher in middle-aged mice compared with
      young mice after Fx-TH. CONCLUSION: These results suggest that age influences the
      lung inflammatory response after Fx-TH.

PMID- 17188090
TI  - Richter's hernia through a Spigelian defect of the abdominal wall.
AB  - A 78-year-old healthy woman with no previous surgeries or history of trauma
      presented with a painful abdominal mass for 1 day. The computed tomography (CT)
      scan of the abdomen demonstrated a partial herniation and strangulation of the
      cecum (Richter's hernia) between the internal and external oblique muscles
      through the linea semilunaris (Spigelian hernia). The challenging clinical
      diagnosis of Spigelian hernias and their surgical treatment options are
      discussed.

PMID- 17188091
TI  - Carotid artery fibromuscular dysplasia.
AB  - Extracranial carotid artery fibromuscular dysplasia (FMD) is a rare finding that
      is frequently incidental and asymptomatic. It usually occurs in middle-age women
      and is secondary to medial fibrodysplasia or, less commonly, intimal
      fibrodysplasia. The carotid artery may be elongated or kinked and associated
      aneurysms have been reported. Symptoms including transient ischemic attack or
      stroke are uncommon and are due to low flow or embolization of platelet
      aggregates. Digital subtraction angiography demonstrates high-grade stenosis with
      the characteristic "string of beads" pattern. Antiplatelet medication with
      sequential imaging is the accepted therapy for asymptomatic lesions. Graduated
      endoluminal dilation under direct vision should be reserved for patients with
      documented lateralizing symptoms.

PMID- 17188092
TI  - Lost gallstones in laparoscopic cholecystectomy: all possible complications.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) has been the gold standard for
      symptomatic gallstones for 15 years. During that time, several studies and case
      reports have been published which outline the possible complications of lost
      gallstones. The aim of this review is to categorize these complications and to
      evaluate the frequency and management of lost gallstones. DATA SOURCES: A Medline
      search from 1987 to 2005 was performed. A total of 111 case reports and studies
      were found, and all reported complications were listed alphabetically. Eight
      studies with more than 500 LCs that reported lost gallstones and perforated
      gallbladder were analyzed for frequency and management of lost gallstones.
      CONCLUSION: Lost gallstones have a low incidence of causing complications but
      have a large variety of possible postoperative problems. Every effort should be
      made to remove spilled gallstones to prevent further complications, but
      conversion is not mandatory.

PMID- 17188093
TI  - The development of physician confidence during surgical and medical internship.
AB  - BACKGROUND: While much research has addressed physician competency, the
      development of confidence has not been studied. We sought to identify which
      elements of internship residents feel most contributed to building their
      confidence. METHODS: By anonymous survey, University of Pennsylvania residents
      rated 104 internship elements for contribution to building physician confidence
      and reported their subjective confidence during and since internship. RESULTS:
      Two hundred ten residents in 18 specialties participated. Detailed ratings for
      all 104 elements are provided. Generally, independent decision-making items and
      good back-up support were equally highly valued, as was developing work
      efficiency. Poorly valued items included high patient loads, long hours, and
      abusive interactions. Surgical and medical residents agreed. Mean confidence
      increased during internship from 12 to 32 (1-100 scale) but remained in the 50s
      during residency for most specialties. CONCLUSIONS: Faculty should make informed,
      deliberate attempts to provide those elements identified as most fostering the
      development of physician confidence.

PMID- 17188094
TI  - Is it feasible to include a technical skill station on a national licensing
      examination?
AB  - The purpose of the current study was to assess the feasibility and validity of
      including a technical skill station on a national licensing examination. At the
      2003 Medical Council of Canada Qualifying Examination, 745 test takers
      participated in a pilot station assessing the ability to perform a technical
      procedure. Checklists and rating scales were used for scoring. Validity was
      investigated by comparing surgery-trained to non-surgery-trained test takers. The
      mean for the pilot station was 72.4%. The pilot station was moderately correlated
      to the rest of the examination (item-total correlation .43). The mean score for
      surgery test takers was higher than for other test takers (P < .001). Inclusion
      of a technical skill station on a high-stakes examination is feasible, and at
      many levels, there is evidence of the validity of including this station.

PMID- 17188095
TI  - Surgical residents as medical student mentors.
AB  - BACKGROUND: Medical students' decreasing interest in surgery may be caused by the
      inadequate availability of role models. We believe that surgical residents show
      the qualities of outstanding surgical mentors and are in a key position to
      influence students' career choices. METHODS: In 2004-2005, 117 medical students
      at Mount Sinai School of Medicine completed their third-year surgery clerkship.
      They were asked to complete an anonymous survey regarding a career in surgery and
      surgical mentors. RESULTS: A total of 107 students (91%) completed the survey.
      Seventy-nine percent were influenced positively toward a surgical career after
      the clerkship. A higher fraction of these students identified a mentor or role
      model than the students who did not increase their interest in surgery (95% vs
      52%). Residents scored higher than attendings in 12 of 14 qualities describing
      outstanding clinical mentors (P < .001). CONCLUSIONS: Role models are crucial in
      bolstering medical students' interest in surgical careers. Residents are
      identified as having qualities that are essential to being an outstanding mentor
      and residents may play a role in influencing students' career choices.

PMID- 17188096
TI  - The resident, the student, and the competencies.

PMID- 17188097
TI  - The use of cognitive task analysis to improve the learning of percutaneous
      tracheostomy placement.
AB  - OBJECTIVE: The purpose of the current study was to determine the effectiveness of
      using cognitive task analysis (CTA) to develop a curriculum to teach the
      behavioral skills and the cognitive strategies of a percutaneous tracheostomy
      (PT) placement. METHODS: Postgraduate 2, 3, and 4 general surgery residents were
      randomly assigned to either the CTA group (N = 9) or the control group (N = 11).
      The CTA group was taught percutaneous tracheostomy placement using the CTA
      curriculum. The control group received the traditional curriculum. RESULTS: The
      CTA group performed significantly higher on the PT procedure at 1 month (CTA:
      43.5 +/- 3.7, control 35.2 +/- 3.9, P = .001) and at 6 months post-instruction
      (CTA: 39.4 +/- 4.2, control: 31.8 +/- 5.8, P = .004). In addition, the CTA group
      demonstrated superior cognitive strategies than the control group (CTA: 25.4 +/-
      5.3, control: 19.2 +/- 2.0, P = .004). CONCLUSIONS: The use of CTA was effective
      in improving the cognitive processes and technical skills of performing a PT for
      surgical residents.

PMID- 17188098
TI  - Proactive versus reactive: the effect of experience on performance in a critical
      care simulator.
AB  - BACKGROUND: We sought to study the cognitive performance of residents in a
      critical care patient simulator. METHODS: Residents in general surgery and
      emergency medicine were recruited to participate in the study. Subjects were read
      a morning report and presented with written data for 4 critical care patients.
      The subjects were evaluated on completing essential clinical tasks, cognitive
      errors, and directionality of reasoning. RESULTS: Nine residents completed the
      study. Months of clinical residency training did not significantly affect
      performance. Residents with more than 10 weeks of intensive care unit (ICU)
      experience (EXP) made significantly fewer cognitive errors than those with less
      than 10 weeks of ICU experience (N-I) (EXP: .75 +/- .96 vs N-I: 7 +/- 5.6 errors
      per subject, P < .05). An unexpected finding was that EXP performed far more
      proactive actions than N-I (EXP: 21.8 +/- 9.9/subject vs N-I: 5.7 +/-
      .6/subjects, P < .01). CONCLUSIONS: A unique finding was that residents with more
      than 10 weeks of ICU experience initiated a large number of proactive actions
      immediately following presentation of patient information, while N-I rarely
      performed these actions. In addition, residents with this degree of experience
      committed significantly fewer cognitive errors. These differences might play a
      role in efficiency, cost, and overall outcome in the care of ICU patients.

PMID- 17188099
TI  - Verbal feedback from an expert is more effective than self-accessed feedback
      about motion efficiency in learning new surgical skills.
AB  - BACKGROUND: Teaching of technical surgical skills to undergraduate medical
      students in a laboratory setting away from the patient is not common practice.
      Because of the large volume of students and shortage of available teaching
      faculty new methods of teaching must be developed for this group of trainees. In
      this study we examined the effectiveness of computer-based video training,
      different types of computer-based motion efficiency feedback (with and without
      expert criteria), and expert feedback on learning of a basic technical skill in
      medical students. METHODS: Forty-five junior medical students were randomized
      into 3 groups and learned suturing and knot-tying skills. Group A received
      computer-generated feedback about the economy of their movements. Group B
      received the same motion economy feedback, as well as expert reference values.
      Group C received verbal feedback from an expert. All groups were pre-tested,
      allowed 18 practice trials, and post-tested, and their skill retention was
      retested after 1 month. Performance was assessed by expert analysis using an
      objective structured analysis of technical skill and by computer analysis
      (Imperial College Surgical Assessment Device [ICSAD]). RESULTS: All groups showed
      improvement from pre-test to post-test. However, only group C showed retention of
      skill on delayed performance testing. CONCLUSIONS: Verbal feedback from an expert
      instructor led to lasting improvements in technical skills performance. Providing
      information about motion efficiency did not lead to similar improvements.

PMID- 17188100
TI  - The open mesh repair of Spigelian hernia.
AB  - BACKGROUND: Spigelian hernias are rare defects of the abdominal wall usually
      appearing between the abdominal muscles, lateral to the rectus abdominis and
      through a debilitated Spigelian aponeurosis. Recently, mesh repair has been
      introduced for the treatment of these types of hernias and different approaches
      have been proposed. METHODS: Nine patients with Spigelian hernia were
      prospectively treated by placing a mesh prosthesis between the external oblique
      and the internal oblique muscles, based on principles of mesh repair established
      by the Lichtenstein group. RESULTS: Five women and 4 men, mean age 75.7 years,
      were operated on. In 1 patient the Spigelian hernia was an incidental finding
      during an inguinal hernia repair. Two patients were operated on an emergency
      basis. Elective operations were undertaken in ambulatory facilities in 3. Two
      patients had postoperative ecchymosis with no associated morbidity. No
      recurrences have been observed during follow-up. CONCLUSIONS: Open mesh repair of
      Spigelian hernias placing the mesh between the external and internal oblique
      muscles is a simple and safe approach that can prevent morbidity related to other
      techniques.

PMID- 17188101
TI  - Minimally invasive video-assisted functional lateral neck dissection for
      metastatic papillary thyroid carcinoma.
AB  - Functional lateral neck dissection requires a large incision providing adequate
      exposure of the surgical field. We evaluated the feasibility of minimally
      invasive video-assisted functional lateral neck dissection (VALNED) in patients
      with papillary thyroid carcinoma (PTC). Low-risk PTC patients with lateral neck
      metastases <2 cm, in absence of any evidence of great vessels involvement, were
      considered eligible. After accomplishing total thyroidectomy and central neck
      clearance, dissection was performed under endoscopic vision by using a technique
      very similar to conventional surgery through the single 4-cm skin incision used
      for thyroidectomy. Two patients were selected: 1 underwent bilateral and 1
      unilateral VALNED. The mean number of the removed nodes was 25 per side. Both
      patients experienced transient postoperative hypocalcemia. No other complication
      occurred. No evidence of residual or recurrent disease was found at follow-up.
      VALNED is feasible, and the results are encouraging. For definitive conclusions,
      larger series and comparative studies are necessary.

PMID- 17188102
TI  - Treatment of renal transplant complications with a mesh hood fascial closure
      technique.
AB  - Early renal allograft dysfunction may be caused by a number of technical factors
      including thrombosis, kinking of vessels, and a Page kidney situation in which
      the allograft is compressed within a shallow false pelvis and limited
      retroperitoneal space. Without early recognition, compromised graft function,
      obstruction, or graft loss may ensue. We describe a technique using a
      polypropylene-assisted mesh hood fascial closure (MHFC) to prevent and treat this
      potential complication. MHFC was performed both primarily to prevent this
      phenomenon, and secondarily to treat this complication. Between April 2001 and
      October 2002, 16 patients undergoing 17 renal transplants underwent MHFC. The
      mean recipient body weight was 17% less than the mean donor weight. The mean
      follow-up period was 9 months. The mean serum creatinine level after primary MHFC
      was 148.4 micromol/L. Three of 4 patients with early allograft dysfunction
      regained function after secondary MHFC and had a mean serum creatinine level of
      155.3 micromol/L. Wound complications were seen in 5 (31%) patients with no wound
      or mesh infections and 1 patient was diagnosed with a lymphocele. We conclude
      that the use of mesh in the primary closure of the incision after renal
      transplantation is safe and has minimal complications.

PMID- 17188103
TI  - Hypersensitivity reaction against patent blue during sentinel lymph node removal
      in three melanoma patients.
AB  - BACKGROUND: In order to identify the sentinel lymph node (SLN) in melanoma
      patients intradermal injection of a radiocolloid tracer and a blue dye are
      commonly used. Life-threatening side effects such as allergic reactions to the
      injected dye have been described. We report 3 cases with systemic allergic
      reactions. METHODS: Three patients suffering from systemic reactions such as
      hypotension and rash during SLN biopsy were tested for sensitisation against
      patent blue and methylene blue with skin prick, scratch, and intradermal test.
      RESULTS: All 3 patients showed positive skin tests to patent blue confirming
      allergic reaction to the injected dye. In addition, all patients showed positive
      skin tests with methylene blue indicating immunologic cross-reactivity between
      patent blue and methylene blue. CONCLUSIONS: Although allergic reactions to blue
      dye during SLN biopsy are rare, they may be life threatening. It is important
      that the attending anesthetist is aware of this.

PMID- 17188104
TI  - Colorectal surgery.

PMID- 17188105
TI  - Surgical critical care.

PMID- 17188106
TI  - Breast surgery.

PMID- 17188107
TI  - Surgical oncology.

PMID- 17188108
TI  - Transplant surgery.

PMID- 17188110
TI  - Prognosis of patients with locally recurrent breast cancer.

PMID- 17188111
TI  - Collaborative infection risk reduction.

PMID- 17188112
TI  - Sleep deprivation in surgeons.

PMID- 17188113
TI  - The value of clinical characteristics and breast imaging studies in predicting a
      histopathologic diagnosis of cancer or high-risk lesion in patients with
      spontaneous nipple discharge.

PMID- 17188115
TI  - Psychosocial associates of premenstrual symptoms and the moderating role of
      social support in a community sample.
AB  - OBJECTIVE: This study aimed to explore the role of psychological factors such as
      perfectionism, need for approval, timidity, and social support from key
      individuals such as a woman's mother and partner in relation to premenstrual
      symptoms in a community (non-help-seeking) sample. METHODS: A large sample of
      women completed a questionnaire to assess whether these proposed factors were
      associated. Premenstrual symptoms were assessed via daily ratings for a period of
      more than 2 months. RESULTS: Perfectionism and low levels of maternal support
      were associated with premenstrual symptoms. In addition, social support from both
      the mother and partner moderated the impact of perfectionism on physical
      symptoms. CONCLUSION: The quality of the relationship with one's mother and
      perceptions of support may play an important role in the experience of cyclical
      symptoms in 'normal' non-help-seeking women. This may interact with preexisting
      personality factors such as perfectionism. Such understandings may ultimately be
      of value in community-based preventative psychoeducational programs.

PMID- 17188114
TI  - Impairment of several immune functions in anxious women.
AB  - OBJECTIVE: Controversial results concerning immune function changes taking place
      in anxious subjects have been obtained. The aim of the present work was to study
      immune function in a group of anxious women. METHODS: Thirty-three anxious and 33
      nonanxious age-matched women were included. Anxiety levels were determined by the
      Beck Anxiety Inventory. Peripheral blood samples were collected, and several
      leukocyte functions, as well as cytokine release, were studied. Plasma cortisol
      levels and total antioxidant capacity were also evaluated. RESULTS: The results
      showed diminished chemotaxis, phagocytosis, lymphoproliferation in response to
      phytohemagglutinin mitogen, natural killer activity, and interleukin-2 release,
      and augmented superoxide anion levels and tumor necrosis factor-alpha release in
      anxious women. Plasma cortisol was increased, while total antioxidant capacity
      was lowered in those subjects. CONCLUSIONS: The findings suggest impaired immune
      function and cytokine release in anxious women. This might be related to
      increased cortisol secretion, which would lead to oxidative stress reflected in
      lowered plasma total antioxidant capacity.

PMID- 17188116
TI  - Coping, affective distress, and psychosocial adjustment among people with
      traumatic upper limb amputations.
AB  - OBJECTIVE: This study investigated the prevalence of symptoms of depression and
      anxiety in a sample of predominantly elderly males with acquired upper limb
      amputations (n=138) and examined the contribution of coping strategies to the
      prediction of psychosocial adjustment. METHOD: One hundred and thirty-eight men
      with injury-related upper limb amputations completed self-report questionnaires
      assessing coping strategies, symptoms of anxiety and depression, and psychosocial
      adaptation to prosthesis use. RESULTS: Prevalence of significant depressive
      symptoms was 28.3% [Hospital Anxiety and Depression Scale, Depression subscale
      (HADS-D) score > or =8]. Prevalence of significant anxiety symptoms was 35.5%
      [HADS Anxiety subscale (HADS-A) score > or =8]. Coping styles emerged as
      important predictors of psychosocial adaptation. In particular, avoidance was
      strongly associated with psychological distress and poor adjustment. CONCLUSIONS:
      These findings suggest the potential benefits of interventions to reduce reliance
      on avoidant coping and stimulate more problem-focused approaches to coping with
      difficulties and challenges in order to facilitate adaptation and prevent
      problems in psychosocial functioning postamputation.

PMID- 17188117
TI  - Do psychological distress and somatization contribute to misattribution of
      asthma? A Chilean study.
AB  - OBJECTIVE: The aim of this study was to assess the association between asthma and
      distress by whether symptoms of asthma present alone or are accompanied by atopy
      or bronchial reactivity to methacholine [bronchial responsiveness (BHR)], hence,
      to ascertain whether overreporting of asthma symptoms occurs in those with
      distress. METHODS: We studied 601 young adults in four groups: those with asthma
      symptoms and atopy or positive BHR, those with asthma symptoms only, those with
      atopy or positive BHR only, and controls. The main independent variables were the
      General Health Questionnaire-12 (GHQ-12) and 45 physical symptoms to assess
      somatization. RESULTS: The somatization score was highly associated with asthma
      symptoms alone and asthma symptoms with BHR or atopy, GHQ-12 with asthma alone
      and asthma and BHR or atopy related to a control group. After adjustment for
      somatization, GHQ-12 was not associated with the asthma outcomes. CONCLUSIONS:
      Excess asthma symptom reporting due to psychological distress or somatization as
      a cause of the association is unlikely.

PMID- 17188118
TI  - The role of depression and anxiety in onset of diabetes in a large population
      based study.
AB  - OBJECTIVE: Recent research has shown that depression may predict incident
      diabetes. The aims of the study are to investigate if symptoms of depression and
      anxiety precede the onset of diabetes or vice versa and to examine if mediating
      factors may explain such associations. METHODS: A prospective population-based
      study (N=37,291) investigating the associations between symptoms of
      depression/anxiety and diabetes was conducted. RESULTS: Individuals reporting
      symptoms of depression and anxiety at baseline had increased risk of onset of
      type 2 diabetes at 10-year follow-up. No gender differences were found. The
      analyses did not reveal underlying factors that mediated the association.
      Baseline diagnosis of diabetes was not associated with subsequent symptoms of
      anxiety or depression among males or females. CONCLUSION: Diabetes did not
      predict symptoms of depression or anxiety. Symptoms of depression and anxiety
      emerged as significant risk factors for onset of type 2 diabetes independent of
      established risk factors for diabetes, such as socioeconomic factors, lifestyle
      factors, and markers of the metabolic syndrome. The comorbidity between
      depression and anxiety may be the most important factor.

PMID- 17188119
TI  - The influence of personality factors on health-related quality of life of
      patients with inflammatory bowel disease.
AB  - OBJECTIVE: The aim of the study was to examine the influence of personality
      factors on health-related quality of life (HRQOL) in patients with inflammatory
      bowel disease (IBD). METHODS: A total of 120 individuals, 60 with ulcerative
      colitis and 60 with Crohn's disease, filled out the Inflammatory Bowel Disease
      Questionnaire, the Rosenberg Self-Esteem Scale, the Neuroticism scale of the
      Eysenck Personality Inventory, and a scale about difficulty describing feelings
      to other people. Sociodemographic and clinical information was also collected.
      RESULTS: Results of hierarchical regression analysis, after controlling for
      possible confounder effects of demographic and clinical variables, showed the
      predictive power of the block of personality variables, accounting for
      significant amounts (13-22%) of variance across the four HRQOL measures. Except
      for self-esteem, which was the factor most closely related to social functioning,
      neuroticism seemed to be the most closely related to the four indicators of
      quality of life. It was also found that greater difficulty in describing feelings
      was linked to poorer HRQOL. CONCLUSION: In summary, some personality factors are
      useful for understanding the process of HRQOL in patients with IBD. Recognizing
      these differences may enrich clinical research and may be crucial when designing
      interventions aimed at treatment effectiveness.

PMID- 17188120
TI  - Clinical features and personality traits associated with psychological distress
      in systemic sclerosis patients.
AB  - OBJECTIVE: The aim of the present study was to identify certain clinical
      parameters and personality characteristics associated with various forms of
      psychopathology in systemic sclerosis (SSc) patients. METHODS: Fifty-six SSc
      patients participated in the study, and 74 healthy participants served as
      controls. A wide range of clinical information was collected, and the following
      self-report instruments were used: General Health Questionnaire, Symptom Distress
      Checklist-90-R, Defense Style Questionnaire, Sense of Coherence (SOC) Scale, and
      Hostility and Direction of Hostility Questionnaire. RESULTS: The odds of being
      assessed with a psychiatric diagnosis upon interview were 4.5 times greater among
      SSc patients compared with controls. Disease duration and lower rates of SOC were
      found to be associated with elevated symptoms of general psychological distress.
      Elevated symptoms of depression were strongly associated with esophageal
      involvement, hostility, and defense style used. Elevated symptoms of anxiety were
      mainly associated with arthritis-related painful conditions and SOC, while
      psychotic-like symptoms were only associated with age and a specific personality
      structure. CONCLUSIONS: SSc patients experience elevated symptoms of
      psychological distress. Several clinical parameters are associated with distress,
      but the role of various personality traits could not be disregarded. Early
      psychiatric assessment and intervention could prevent psychological distress in
      SSc patients.

PMID- 17188121
TI  - Increase in dermcidin-derived peptides in sweat of patients with atopic eczema
      caused by a humorous video.
AB  - OBJECTIVE: Dermcidin (DCD)-derived peptide is an antimicrobial peptide produced
      by the sweat glands. However, the levels of DCD-derived peptide in sweat were
      decreased in patients with atopic eczema (AE). The effect of viewing a humorous
      video on the levels of DCD-derived peptide was studied. METHODS: Twenty patients
      with AE viewed an 87-min humorous video (Modern Times, featuring Charlie
      Chaplin). Just before and immediately after viewing, sweat was collected, and the
      levels of DCD-derived peptide and total protein in sweat were measured. RESULTS:
      Viewing a humorous video increased the levels of DCD-derived peptide without
      affecting the levels of total protein in sweat. CONCLUSION: Viewing a humorous
      video increased DCD-derived peptide in sweat of patients with AE, and thus, it
      may be helpful in the treatment of skin infection of AE.

PMID- 17188122
TI  - MMPI-2 validity, clinical and content scales, and the Fake Bad Scale for personal
      injury litigants claiming idiopathic environmental intolerance.
AB  - BACKGROUND: Idiopathic environmental intolerance (IEI) is a descriptor for
      nonspecific complaints that are attributed to environmental exposure. METHODS:
      The Minnesota Multiphasic Personality Inventory 2 (MMPI-2) was administered to 50
      female and 20 male personal injury litigants alleging IEI. RESULTS: The validity
      scales indicated no overreporting of psychopathology. Half of the cases had
      elevated scores on validity scales suggesting defensiveness, and a large number
      had elevations on Fake Bad Scale (FBS) suggesting overreporting of
      unauthenticated symptoms. The average T-score profile for females was defined by
      the two-point code type 3-1 (Hysteria-Hypochondriasis), and the average T-score
      profile for males was defined by the three-point code type 3-1-2 (Hysteria,
      Hypochondriasis-Depression). On the content scales, Health Concerns (HEA) scale
      was significantly elevated. CONCLUSION: Idiopathic environmental intolerance
      litigants (a) are more defensive about expressing psychopathology, (b) express
      distress through somatization, (c) use a self-serving misrepresentation of
      exaggerated health concerns, and (d) may exaggerate unauthenticated symptoms
      suggesting malingering.

PMID- 17188123
TI  - The continuum model of obligatory exercise: a preliminary investigation.
AB  - OBJECTIVE: The aim of this study was to carry out a preliminary study of the
      proposed Continuum Model of Obligatory Exercise, which states that obligatory
      exercise lies on a continuum--a continuum that is characterized not only by
      differences in severity, but by qualitative differences in the way the syndrome
      manifests, as the behaviour changes from mildly obsessive attitudes to exercise,
      to extremely disordered attitudes to exercise, which are accompanied by an eating
      disorder. METHOD: Structural equation modelling (SEM) was used to investigate the
      Continuum Model of Obligatory Exercise utilizing data from a longitudinal study
      of female triathletes. RESULTS: The structural model specifying the hypothesized
      causal pathways confirmed many of the postulates of the Continuum Model of
      Obligatory Exercise, including the role of weight and shape preoccupation in
      predicting food restriction, eating disorder behaviour, and increased obligatory
      exercise behaviour, as well as the role of obsessive-compulsiveness and increased
      physical activity in predicting eating disorder behaviour in exercisers.
      CONCLUSION: The structural model investigated is reasonable and can serve as a
      starting point for a theory-based empirical exploration of the notion that
      obligatory exercise behaviour lies on a continuum.

PMID- 17188124
TI  - The role of dysfunctional beliefs and attitudes in late-life insomnia.
AB  - OBJECTIVES: This study examined the role of individual and combined sleep-related
      dysfunctional beliefs in late-life insomnia. METHODS: Older adults who responded
      to an advertisement in a magazine took part in a cross-sectional survey (N=382).
      Respondents completed self-report measures of dysfunctional beliefs about sleep
      (Dysfunctional Beliefs and Attitudes to Sleep Scale) as well as measures of their
      current sleep patterns. RESULTS: Overall, people with insomnia (PWI) endorsed
      more extreme ratings of dysfunctional beliefs than "good sleepers" did. However,
      some sleep-related dysfunctional beliefs did not discriminate PWIs from good
      sleepers nor were they related to experiencing a longer duration of insomnia.
      CONCLUSION: This article demonstrates that not all sleep-related dysfunctional
      beliefs are related to reporting insomnia and that some are not related to a
      longer reported duration of insomnia, possibly changing through personal
      experience. These preliminary results may have implications for tailoring the
      cognitive aspects of psychoeducational programmes for people with late-life
      insomnia.

PMID- 17188125
TI  - The low-dose dexamethasone suppression test in fibromyalgia.
AB  - OBJECTIVE: Fibromyalgia syndrome (FMS) has been associated with decreased
      cortisol secretion. Patients with posttraumatic stress disorder (PTSD) exhibit
      similar hypocortisolism in the context of increased negative feedback sensitivity
      of the hypothalamic-pituitary-adrenal (HPA) axis. Because trauma and PTSD have
      been associated with fibromyalgia, we evaluated whether patients with
      fibromyalgia demonstrate increased HPA feedback sensitivity. METHOD: Baseline
      blood samples were obtained at 0800 h, and 0.5 mg of dexamethasone was
      administered to 15 female patients with FMS and 20 normal controls at 2300 h.
      Adrenocorticotropin (ACTH), cortisol, and dexamethasone levels were measured at
      0800 h after dexamethasone intake. RESULTS: There were no group differences in
      mean ACTH or cortisol levels or in ACTH/cortisol ratio at baseline. After
      dexamethasone intake, patients with FMS exhibited more pronounced suppression of
      cortisol but not of ACTH, as well as increased ACTH/cortisol ratios compared with
      controls. Percent cortisol suppression was associated with pain and fatigue,
      while ACTH/cortisol ratio and dexamethasone availability were associated with
      stress and anxiety measures. CONCLUSION: Our results suggest increased
      sensitivity to glucocorticoid feedback, manifested at the adrenal level, in FMS.

PMID- 17188126
TI  - Psychosocial vulnerability predicts psychosocial outcome after an organ
      transplant: results of a prospective study with lung, liver, and bone-marrow
      patients.
AB  - OBJECTIVE: The pretransplant medical evaluation of transplantation candidates
      includes an assessment of psychosocial data. This study investigates psychosocial
      vulnerability as a predictor of posttransplant outcome. METHODS: Seventy-six
      patients were assessed prior to lung, liver, or bone-marrow transplant.
      Pretransplant vulnerability markers were cognitive beliefs (sense of coherence
      and optimism), affect (anxiety and depression), and external resources (social
      support). In addition, psychosocial functioning was assessed by professionals.
      Quality of life, general life satisfaction, need for counseling, and survival
      rate were assessed 12 months after transplant. RESULTS: Pretransplant variables
      explain 21-40% of the variance in posttransplant psychosocial outcome variables.
      Cognitive beliefs predict mental quality of life; affect (depression) and social
      support predict life satisfaction; and expert-rated psychosocial functioning
      predicts life satisfaction and need for counseling. CONCLUSION: The
      multidimensional vulnerability model is suitable for predicting posttransplant
      psychosocial outcome. Patients with high pretransplant vulnerability should
      receive ongoing psychosocial counseling.

PMID- 17188127
TI  - Anxiety and depression after lung transplantation: Mirtazapine as a first-choice
      agent?

PMID- 17188128
TI  - The case for liaison psychiatry for older adults.

PMID- 17188129
TI  - Presidential address: Harvey Cushing: the artist.

PMID- 17188130
TI  - Adrenal venous sampling in primary hyperaldosteronism: comparison of radiographic
      with biochemical success and the clinical decision-making with "less than ideal"
      testing.
AB  - BACKGROUND: Adrenal venous sampling (AVS) is used in the workup of primary
      hyperaldosteronism (PA). The purpose of this study was to determine the success
      rate of AVS and to examine the decision-making process after "less than ideal"
      AVS. METHODS: A total of 60 patients underwent 62 AVS for PA. Biochemical
      evidence of adrenal vein cannulization was analyzed with adrenal-peripheral
      cortisol ratios. Pathology and clinical outcomes were reviewed in patients
      undergoing adrenalectomy. RESULTS: Bilateral cannulization was confirmed in only
      21% (pre-adrenocorticotropic hormone [ACTH] infusion) and 44% (post-ACTH
      infusion) AVS. Of 39 patients who underwent adrenalectomy for presumed unilateral
      disease, only 16 patients had "ideal" AVS, and 18 patients had only unilateral
      cannulization on AVS. Despite this, 11 appeared to lateralize and 7 had imaging
      to support unilateral disease. Postoperatively, 15 (82%) had a significant
      reduction in their blood pressure, and 7 (39%) of these were cured. Surgery
      failed in 2 patients; both were found to have bilateral hyperplasia. Bilaterally
      unsuccessful cannulization (n = 5) still lateralized in 3 patients, and 2
      patients had nodules on computed tomography scan. All 5 patients had significant
      reduction in blood pressure, and 2 were cured. CONCLUSIONS: ACTH infusion during
      AVS enhances the biochemical evidence of adrenal vein cannulization. Following
      "less than ideal" AVS, clinical decisions can still be made using anatomic and
      partial AVS data.

PMID- 17188131
TI  - Radionuclide imaging for hyperparathyroidism (HPT): which is the best technetium
      99m sestamibi modality?
AB  - BACKGROUND: To determine the utility of available radionuclide imaging modalities
      for preoperative parathyroid localization, we compared the accuracy of 4 types of
      technetium-99m ((99)Tc) sestamibi-based scans. METHODS: Over 5 years, 833
      patients with sporadic primary hyperparathyroidism underwent either (99)Tc
      sestamibi with planar views (Planar; n = 138); sestamibi single photon emission
      computed tomography (SPECT; n = 165); SPECT with thyroid (123)I-subtraction phase
      (SPECT/(123)I; n = 350); or SPECT combined with conventional CT (SPECT/CT; n =
      180). The accuracy of each modality was determined on the basis of intraoperative
      parathyroid pathology, defined as single adenoma or multigland disease. RESULTS:
      Planar scans had significantly more false negatives (no tumor visualized) than
      SPECT-based scans (P < 0.01), but positive predictive values were similar. A
      false-negative scan was present in 38% of Planar scans, 27% SPECT, 4%
      SPECT/(123)I, and 17% SPECT/CT, with single adenoma found at operation in 77%,
      64%, 53%, and 74%, respectively. When a scan had a single focus of uptake, SA was
      found at that location in 77%, 85%, 68%, and 87%, respectively. SPECT,
      SPECT/(123)I, and SPECT/CT did not significantly reduce the false-positive rate.
      CONCLUSIONS: We recommend obtaining multiplanar SPECT-based imaging, which offers
      3-dimensional localization and improved detection of parathyroid tumors when
      compared with Planar scans. A negative scan did not predict multigland disease.

PMID- 17188132
TI  - The role of intraoperative neuromonitoring of recurrent laryngeal nerve during
      thyroidectomy: a comparative study on 1000 nerves at risk.
AB  - BACKGROUND: The role of intraoperative neuromonitoring of recurrent laryngeal
      nerve (RLN) during thyroidectomy has not been well established. The present study
      evaluates whether RLN injury can be reduced by the application of this technique
      during thyroidectomy in a single center. METHODS: Of 1000 RLNs that were at risk
      of injury in 639 consecutive patients who underwent thyroidectomy, the outcome of
      501 RLNs with the use of neuromonitoring was compared with that of 499 nerves
      that were operated by routine identification only. The incidences of RLN
      paralysis were compared between the 2 groups and the assigned risk subgroups.
      RESULTS: Postoperative palsy was identified in 47 RLNs (4.7%), with complete
      recovery in 37 of 44 RLNs (84%) without documented injury. The overall incidence
      of postoperative RLN paralysis was significantly higher during thyroidectomy for
      malignancy (P = .025) and secondary thyroidectomy (P = .017). There was no
      significant difference in postoperative, transient, and permanent paralysis rates
      between the neuromonitoring and control groups. In subgroup analysis, the
      postoperative RLN palsy rate was higher during reoperative thyroidectomy (19% vs
      4.6%; P = .019) in the control group but not in the neuromonitoring group (7.8%
      vs 3.8%; P > .05). CONCLUSION: Neuromonitoring of the RLN during thyroid surgery
      could not be demonstrated to reduce RLN injury significantly, compared with the
      adoption of routine RLN identification. However, its application can be
      considered for selected high-risk thyroidectomies.

PMID- 17188133
TI  - Cost-effectiveness analysis of parathyroidectomy for asymptomatic primary
      hyperparathyroidism.
AB  - BACKGROUND: Controversy exists concerning the best treatment for asymptomatic
      primary hyperparathyroidism (PHPT) when the National Institutes of Health
      consensus conference criteria for parathyroidectomy are not met. We hypothesized
      that parathyroidectomy would be more cost-effective than observation or
      pharmacologic therapy for these patients. METHODS: Cost-effectiveness analysis
      was performed comparing treatment strategies for asymptomatic PHPT. Treatment
      outcomes, their probabilities, and costs were identified on the basis of
      literature and cost database review. Outcomes were weighted by using established
      quality-of-life utility factors. Sensitivity analysis was used to examine the
      uncertainty of costs and utility estimates in the model. RESULTS: The incremental
      cost-effectiveness ratio for parathyroidectomy was US dollars 4778 per quality
      adjusted life year (QALY) gained. Operation remained cost-effective until the
      average cost of parathyroidectomy increased from the estimated value of US
      dollars 4778 to US dollars 14,650. Pharmacologic therapy was not cost-effective
      unless the annual cost of therapy decreased from an estimated US dollars 7406
      (for cinacalcet) to US dollars 221. Parathyroidectomy ceases to be preferred over
      monitoring if a quality-of-life difference is not demonstrable after curative
      operation. CONCLUSIONS: Parathyroidectomy is more cost-effective than observation
      for managing asymptomatic PHPT patients who do not meet National Institutes of
      Health criteria for parathyroidectomy. Furthermore, pharmacologic therapies with
      a greater than US dollars 221 annual cost were not cost-effective in this model.

PMID- 17188134
TI  - Interpretation of intraoperative parathyroid hormone monitoring in patients with
      baseline parathyroid hormone levels of <100 pg/mL.
AB  - BACKGROUND: Common guidelines for intraoperative parathyroid hormone (IOPTH)
      interpretation are based on clearly elevated baseline parathyroid hormone (PTH)
      values. We hypothesize that patients with low-baseline levels (<100 pg/mL) have a
      higher incidence of multigland disease (MGD) and display differences in PTH
      kinetics compared with patients with high-baseline levels. METHODS: We
      retrospectively reviewed the cases of 1151 patients with primary
      hyperparathyroidism who underwent parathyroidectomy with IOPTH monitoring. Of
      these, 141 patients had low-baseline values. Multiple comparisons were made
      between the low-baseline and high-baseline groups. RESULTS: Twenty-six percent of
      the low-baseline patients had MGD versus 15% of the high-baseline patients (P =
      .002). The PTH kinetics differed between groups after gland excision at both 5
      and 10 minutes. Adherence solely to the "50% rule" during minimally invasive
      parathyroidectomy potentially would have missed 25% of patients with MGD in the
      low-baseline group versus 10% in the high-baseline group; 5.7% of the low
      baseline patients had persistent or recurrent hypercalcemia versus 2.9% of the
      high-baseline patients. CONCLUSION: MGD is significantly more prevalent among low
      baseline patients, and PTH kinetics are somewhat different between groups. The
      current guidelines that are used for IOPTH monitoring may not be ideal for use in
      this low-baseline group and will likely need to be revised after further study of
      this group of patients.

PMID- 17188135
TI  - Operative resection of primary carcinoid neoplasms in patients with liver
      metastases yields significantly better survival.
AB  - BACKGROUND: It is unclear whether there is a benefit to resection of primary
      gastrointestinal carcinoid neoplasm with hepatic metastases. We investigated
      whether primary tumor resection in this setting led to a significant difference
      in outcomes. METHODS: A retrospective review of patients with abdominal carcinoid
      neoplasms between 1995 and 2006 was performed. Data collected on patients with
      proven carcinoid liver metastases at initial diagnosis included whether the
      primary neoplasm was resected, time to progression of liver metastases, and
      status at last follow-up. Progression-free survival and survival were calculated
      by the method of Kaplan-Meier and compared by the log-rank test. RESULTS: There
      were 84 patients, 60 of whom had their primary neoplasm resected. The resected
      group had a greater median progression-free survival of 56 months, compared with
      25 months for the primary nonresected group (P < .001). Median survival time for
      the resected group was longer at 159 months, compared with 47 months for the
      nonresected group (P < .001). CONCLUSIONS: Resection of the primary neoplasm is
      associated with better progression-free survival and overall survival in patients
      with abdominal carcinoid neoplasms. Therefore, localization and resection of the
      primary neoplasm should be considered, even among patients in whom the primary
      neoplasm is asymptomatic.

PMID- 17188136
TI  - Patterns of expression of cell cycle/apoptosis genes along the spectrum of
      thyroid carcinoma progression.
AB  - BACKGROUND: Genetic screening studies suggest that genetic changes underlie
      progression from well differentiated to anaplastic thyroid cancers. The aim of
      this study is to determine to what extent cell cycle/apoptosis regulators
      contribute to cancer progression. METHODS: Tissue microarrarys (TMAs) were
      constructed from well-differentiated papillary thyroid carcinoma (WDPTC; n = 41),
      poorly differentiated thyroid carcinoma (PDTC; n = 43), and anaplastic thyroid
      carcinoma (ATC; n = 22). TMAs were immunostained for 7 different cell
      cycle/apoptosis-related genes (p53, Ki-67, bcl-2, mdm-2, cyclin D1, p21, and
      p27). RESULTS: p53 (0%, 12%, 32%) and Ki-67 (5%, 49%, 82%) were expressed with
      increasing frequency, and bcl-2 (68%, 42%, 0%) and p21 (40%, 7%, 0%) with
      decreasing frequency in WDPTC to PDTC and ATC, respectively (P < .001).
      Interestingly, mdm-2 (54%, 5%, 0%) showed decreased expression along the
      progression axis (P < .001). p27 and cyclin D1 were expressed in <15% of cases,
      with a trend toward decreasing expression from WDPTC to PDTC to ATC. CONCLUSIONS:
      These data confirm the presence of increasing genetic complexity with progressive
      dedifferentiation in thyroid cancer, with aberrant tumor suppressor activity and
      increased proliferative activity being most prevalent in ATC. The data also
      confirm the intermediate position of PDTC in the classification scheme of thyroid
      carcinomas.

PMID- 17188137
TI  - Localization of hyperfunctioning parathyroid glands by selective venous sampling
      in reoperation for primary or secondary hyperparathyroidism.
AB  - BACKGROUND: Localization of hyperfunctioning parathyroid glands in patients with
      previous cervical operations is not always successful with noninvasive methods
      such as ultrasound, sestamibi scan, or magnetic resonance imaging. The aim of our
      study was to evaluate the results of selective venous sampling (SVS) of intact
      parathyroid hormone (PTH) in patients undergoing surgery for primary (75%) or
      secondary (25%) hyperparathyroidism (HPT). METHODS: Between January 2000 and
      January 2006, SVS for PTH was performed in 51 consecutive patients with
      persistent or recurrent HPT or patients with previous cervical explorations. The
      results of SVS were compared with those of noninvasive localization studies.
      RESULTS: Successful surgical treatment was achieved in 47 of 51 patients (92%).
      SVS had a sensitivity of 83.3% for the correct localization of a parathyroid
      adenoma (79.5%) or hyperplastic parathyroid glands (91.6%). False-positive or
      indeterminate results of SVS were found in 6% and 2%, respectively, of the
      patients. Ultrasound detected enlarged parathyroid glands with a sensitivity of
      33.3%, and sestamibi scan with a sensitivity of 57.1%. CONCLUSIONS: Compared with
      noninvasive localization studies, SVS for PTH yielded the best results for
      recurrent or persistent HPT and for patients with previous neck explorations. SVS
      is strongly recommended in reoperative surgery for HPT with indeterminate results
      of noninvasive methods.

PMID- 17188138
TI  - Outcomes of adrenal cortical carcinoma in the United States.
AB  - BACKGROUND: Improvements in the sensitivity of radiographic imaging have lead to
      an increase in the number of adrenal masses diagnosed. The purpose of this study
      is to determine if technologic advancements have resulted in the diagnosis of
      earlier-staged adrenal cortical cancer (ACC) and to determine if the survival of
      patients with ACC has improved over the past 15 years. METHODS: Patients with ACC
      were identified in the Surveillance, Epidemiology, and End Results database
      between 1988 and 2002. Changes in demographics, stage, size, and treatment were
      analyzed by standard statistical testing. RESULTS: We identified 602 patients
      with a mean age of 53 years and an average tumor size of 11.8 cm. Two hundred
      thirty-eight (39.5%) patients presented with localized disease (stages I and II),
      and 311 (52%) patients presented with advanced disease (stages III and IV). The
      comparison of smaller lesions and number of patients were 5 to 6 cm in 24 (4%)
      patients, 4 to 5 cm in 27 (4.5%) patients, and <4 cm in 19 (3.1%) patients.
      Patients with masses less than 5 cm were statistically more likely to have
      localized disease (P <. 001). Age (P = .10), tumor size (P = .85), tumor stage (P
      = .45), and 5-year survival (P = .5) did not change over the 15-year study.
      CONCLUSIONS: Over the 15-year study, patients with ACC were not diagnosed at an
      earlier stage or with tumors smaller, and survival did not improve.

PMID- 17188139
TI  - Recognizing genes differentially regulated in vitro by the multiple endocrine
      neoplasia type 1 (MEN1) gene, using RNA interference and oligonucleotide
      microarrays.
AB  - BACKGROUND: Data on downstream effects of MEN1 gene inactivation is scarce. In an
      effort to identify genes regulated by MEN1, we designed a silencing experiment in
      a human endocrine pancreatic tumor cell line (BON1). METHODS: By using RNA
      interference, MEN1 mRNA expression was knocked-down by >85%. Gene expression was
      assessed by oligonucleotide microarrays and compared to expression in nonsilenced
      controls. We also investigated if genes were differentially expressed in 6
      malignant endocrine pancreatic tumors (EPTs) with homozygous MEN1 inactivation
      compared to 2 without MEN1 gene alterations. RESULTS: Using a cut-off of > or =2
      times, 66 genes were found to be upregulated, and 22 were downregulated in the
      MEN1-silenced clones. We corroborated the microarray findings by performing
      quantitative-PCR on the RNA from the silencing experiments for 7 of the 88
      differentially regulated genes. Genes involved in endocrine cell fate
      determination, as well as genes known to be involved in NFkappaB, Notch, and Wnt
      signaling pathways, were among genes verified as differentially regulated in
      vitro. CONCLUSIONS: The demonstration of pathways affected by silencing of MEN1
      in vitro provides novel insight into neoplastic processes of potential importance
      in vivo, which warrants further study.

PMID- 17188141
TI  - Four-dimensional computed tomography permits preoperative planning for directed
      parathyroidectomy.

PMID- 17188140
TI  - Improved preoperative planning for directed parathyroidectomy with 4-dimensional
      computed tomography.
AB  - BACKGROUND: Four-dimensional computed tomography (4D-CT) provides both functional
      and highly detailed anatomic information about parathyroid tumors. The purpose of
      this study was to compare 4D-CT with sestamibi imaging and ultrasonography as
      methods for the accurate preoperative localization of hyperfunctioning
      parathyroid glands before parathyroidectomy. METHODS: A study of 75 patients with
      primary hyperparathyroidism was performed at a tertiary-care institution.
      Sestamibi imaging, ultrasonography, and 4D-CT were performed on each patient
      preoperatively. Results of the imaging studies were compared with operative
      findings, pathologic data, and biochemical measurements to assess the sensitivity
      and specificity of each of the imaging modalities. RESULTS: 4D-CT demonstrated
      improved sensitivity (88%) over sestamibi imaging (65%) and ultrasonography
      (57%), when the imaging studies were used to localize (lateralize)
      hyperfunctioning parathyroid glands to 1 side of the neck. Moreover, when used to
      localize parathyroid tumors to the correct quadrant of the neck (ie, right
      inferior, right superior, left inferior, or left superior), the sensitivity of 4D
      CT (70%) was significantly higher than sestamibi imaging (33%) and
      ultrasonography (29%). CONCLUSION: 4D-CT provides significantly greater
      sensitivity than sestamibi imaging and ultrasonography for precise (quadrant)
      localization of hyperfunctioning parathyroid glands. This allows improved
      preoperative planning, particularly for the case of reoperation. In addition to
      the data that are provided, we present a novel classification scheme for use in
      parathyroid localization.

PMID- 17188142
TI  - Posterior retroperitoneoscopic adrenalectomy--results of 560 procedures in 520
      patients.
AB  - BACKGROUND: The posterior retroperitoneoscopic adrenalectomy is less popular than
      the laparoscopic transabdominal method. Due to the direct approach to the adrenal
      glands, however, the posterior retroperitoneal access is easy to use and may
      offer advantages not available with other endoscopic procedures for
      adrenalectomy. METHODS: Between July 1994 and March 2006, we performed 560
      adrenalectomies (right side: n = 258; left side: n = 302) by the posterior
      retroperitoneoscopic approach in 520 patients (200 male, 320 female; age, 10 to
      83 years). Of the 520 patients, 21 suffered from Cushing's disease, 499 patients
      had adrenal tumors (157 Conn's adenomas, 120 pheochromocytomas [13 bilateral],
      110 Cushing's adenomas [6 bilateral], and 112 other tumors). Tumor size ranged
      from 0.5 to 10 cm (mean, 2.9 +/- 1.7 cm). The procedures were performed with the
      patients in the prone position usually with 3 trocars. RESULTS: Mortality was
      zero. Conversions to open or laparoscopic lateral surgery were necessary in 9
      patients (1.7%). Major complications occurred in 1.3% of patients, minor
      complications in 14.4%. Mean operating time was 67 +/- 40 min and declined
      significantly (P < .001) from the early procedures (106 +/- 46 min) to the later
      operations (40 +/- 15 min). CONCLUSIONS: The posterior retroperitoneoscopic
      adrenalectomy is a safe and fast procedure. In experienced hands, this method
      represents the ideal approach in adrenal surgery.

PMID- 17188143
TI  - On "Posterior retroperitoneoscopic adrenalectomy--results of 560 procedures in
      520 patients".

PMID- 17188144
TI  - Long-term results and functional outcome after cervical evisceration in patients
      with thyroid cancer.
AB  - BACKGROUND: Surgical strategy in patients with thyroid cancer (TC) infiltrating
      the aerodigestive system is controversial. This study was undertaken to examine
      the long-term results of cervical evisceration (CE). PATIENTS AND METHODS: Since
      1995, 14 consecutive patients with advanced TC underwent total laryngectomy (LE,
      n = 6) or esophagolaryngectomy (ELR, n = 8). Patients with unusual thyroid
      neoplasms or metastases to the thyroid (n = 3) were excluded. For esophageal
      reconstruction, free jejunal grafts (n = 6) and gastric tubes (n = 2) were used.
      RESULTS: Procedure-related morbidity and mortality were 42% and 14%,
      respectively. ELR was associated with a significant higher frequency of
      complications and reoperations compared with LE. Twelve-month and 30-month
      survival rates were 73% and 55%, respectively; 85% of the patients were satisfied
      with the surgical results. There were no long-term problems concerning food
      intake in the ELR patients. Two ELR patients were able to learn a substitutive
      voice. CONCLUSIONS: Cervical evisceration in patients with TC is associated with
      significant perioperative morbidity and mortality requiring careful patient
      selection. Regarding long-term survival, local tumor control, and patient's
      satisfaction, however, CE should be taken into account in suitable patients with
      advanced TC.

PMID- 17188146
TI  - Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic
      neuroendocrine tumors.
AB  - BACKGROUND: Treatment with (90)Y- or (177)Lu-DOTATOC has recently been introduced
      in the palliative treatment of somatostatin receptor-expressing neuroendocrine
      tumors (NETs). The aim of the study was to present clinical experience with (90)Y
      and (177)Lu-DOTATOC therapy in the management of NET. METHODS: To prove
      suitability for treatment each patient underwent scanning with (111)In-DTPAOC or
      (68)Ga-DOTATOC positron emission tomography/computed tomography. All patients
      received [(90)Y-DOTATOC] as initial treatment. In case of disease relapse the
      treatment was repeated. To avoid side effects of repeated [(90)Y] applications, a
      switch to [(177)Lu-DOTATOC] was carried out. Clinical, biochemical, and
      radioimaging responses were documented. RESULTS: Twenty patients with metastatic
      nonresectable NETs (15 pancreas NETs, 2 midgut NETs, 1 gastrinoma, 1
      paraganglioma, 1 NET of unknown primary origin) were included. In 8 patients the
      treatment was repeated more than once (mean, 3 times; range, 2-5 times). After
      [(90)Y] treatment moderate toxicity was observed in 8 patients. No serious
      adverse events were documentable. After restaging, a partial remission was found
      in 5 patients, stable disease in 11 patients, and tumor progression in 4
      patients. CONCLUSIONS: Peptide receptor-targeted radionuclide therapy is a
      promising, safe, and feasible approach in the palliative therapy of patients with
      NET.

PMID- 17188145
TI  - A phase II trial of rosiglitazone in patients with thyroglobulin-positive and
      radioiodine-negative differentiated thyroid cancer.
AB  - BACKGROUND: Rosiglitazone is a peroxisome proliferator-activated receptor gamma
      (PPARgamma) agonist that has been shown to induce differentiation, cell cycle
      arrest, and apoptosis in a variety of human cancers including thyroid cancer.
      METHODS: Ten patients with differentiated thyroid cancer were enrolled in an open
      label, phase II trial of oral rosiglitazone treatment (4 mg daily for 1 week,
      then 8 mg daily for 7 weeks). The levels of PPARgamma receptor mRNA and protein
      expression were determined in the patient's neoplasm. RESULTS: Of 10 patients, 4
      had positive radioiodine scans after rosiglitazone therapy with uptake in the
      neck in 3 patients and in the pelvis in 1 patient. After treatment, the serum
      thyroglobulin level decreased in 2 patients, increased in 5 patients, and was
      stable in 3 patients. No patient developed clinically important toxicity
      associated with rosiglitazone treatment. We found no relationship in the level of
      PPARgamma mRNA and protein expression in patients who had radioiodine uptake
      compared with those who did not. CONCLUSIONS: Our findings suggest that
      rosiglitazone treatment may induce radioiodine uptake in some patients with
      thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer. We
      found no relationship between the expression level of the PPARgamma mRNA and
      protein in the neoplasm and radioiodine uptake status after rosiglitazone
      therapy, questioning the potential pathway of effect.

PMID- 17188147
TI  - Changes of the speaking and singing voice after thyroid or parathyroid surgery.
AB  - BACKGROUND: While permanent dysphonia is a rare complication of thyroid or
      parathyroid surgery, postoperative changes of the speaking and/or singing voice
      often remain unrecognized. METHODS: In a prospective 4-arm study, vocal fold
      videolaryngostroboscopy and functional assessment of pre- and postoperative vocal
      performance was used to evaluate voice disturbances in 120 patients undergoing
      extended cervical surgery and in 19 patients with limited interventions for
      thyroid and/or parathyroid pathology. RESULTS: Impairments, especially of the
      singing voice, were predominantly observed after extended endocrine neck surgery.
      In women, the highest pitch of the singing voice (HPS) dropped from 651 Hz to 563
      Hz (E5 to Csharp5, P < .001). In men, the HPS decreased to a lesser extent (423
      Hz to 374 Hz, (Gsharp4 to Fsharp4, P = .009). Covariant analysis of influencing
      factors revealed the preoperative maximum frequency range and the HPS as
      predictors of the postoperative voice outcome. CONCLUSIONS: While alterations of
      the speaking voice after thyroid and parathyroid surgery usually remain
      subclinical, transient changes of the singing voice will matter to voice
      professionals.

PMID- 17188148
TI  - Less-than-subtotal parathyroidectomy increases the risk of persistent/recurrent
      hyperparathyroidism after parathyroidectomy in tertiary hyperparathyroidism after
      renal transplantation.
AB  - BACKGROUND: The optimal surgical approach for tertiary hyperparathyroidism (HPT)
      after kidney transplantation is unknown. Existing studies are limited by small
      sample size, lack of adjustment for kidney function, and no long-term follow-up.
      METHODS: We retrospectively analyzed 74 patients with tertiary HPT who underwent
      parathyroidectomy at two centers since 1978. Persistent HPT was defined as
      parathyroid hormone (PTH) concentrations in excess of the K/DOQI target range for
      the corresponding estimated creatinine clearance (eCrCl). RESULTS: Seventy-four
      patients had 83 operations (72 subtotal and 11 less-than-subtotal
      parathyroidectomies). Mean follow-up time was 5.4 +/- 4.7 years. Calcium
      concentrations decreased significantly after parathyroidectomy (2.83 vs 2.28
      mmol/L, P < 0.001), as did eCrCl (54.5 vs 44.9 mL/min, P < 0.001) and PTH (382 vs
      132 pg/mL, P < 0.001). In the multivariable regression analysis, only the type of
      operation and postoperative eCrCl were significantly correlated with PTH at
      follow-up. A limited parathyroidectomy was associated with a fivefold increase in
      risk of persistent or recurrent hyperparathyroidism. CONCLUSIONS: The use of
      limited parathyroidectomy for tertiary HPT after kidney transplantation has a
      higher risk of persistent/recurrent HPT. Subtotal parathyroidectomy is
      recommended for patients with tertiary HPT.

PMID- 17188149
TI  - Routine ipsilateral level VI lymphadenectomy reduces postoperative thyroglobulin
      levels in papillary thyroid cancer.
AB  - BACKGROUND: Lymphadenectomy in clinically node-negative papillary thyroid cancer
      (PTC) is controversial. The aim of this study is to determine whether routine
      ipsilateral level VI lymphadenectomy (LNDVI) has advantages over total
      thyroidectomy (TT) alone. METHODS: A retrospective cohort study was performed.
      Patients undergoing surgery for clinically node-negative PTC >1 cm were included.
      Group A had TT and LNDVI. Group B had TT alone. The number of radioiodine
      treatments and postablative stimulated serum thyroglobulin (TG) levels were
      compared. RESULTS: From 1995 to 2005, 447 patients with clinically node-negative
      PTC underwent surgery. Group A (n = 56) had TT and LNDVI. Group B (n = 391) had
      TT alone. Tumor size was equivalent (group A, 20 mm; group B, 23 mm; P = .14) as
      were MACIS (metastasis, age, completeness of resection, invasion, and size)
      scores (group A, 4.70; confidence interval, 4.23-5.17; group B, 4.73; confidence
      interval, 4.4-5.05). Serum postablative TG levels were lower in group A (0.4
      microg/L) compared with group B (9.3 microg/L), P = .02. More patients had
      undetectable TG levels in group A (72%) than in group B (43%) (P < .001). Long
      term complications rates were the same. CONCLUSIONS: In PTC the addition of
      routine LNDVI results in lower postablation levels of TG and higher rates of
      athyroglobulinemia when compared with TT alone.

PMID- 17188150
TI  - Routine central neck lymph node dissection for thyroid carcinoma.

PMID- 17188151
TI  - Apoptosis-mediated medullary thyroid cancer growth suppression by the PI3K
      inhibitor LY294002.
AB  - BACKGROUND: Medullary thyroid cancer (MTC) cells exhibit frequent activation of
      the PI3K pathway as evidenced by the presence of hyperactivation of Akt kinases
      and overexpression of neuroendocrine (NE) markers. We hypothesized that the
      inhibition of the PI3K pathway in MTC may lead to a reduction in cell growth and
      NE tumor marker production. METHODS: Human MTC-TT cells were treated with the
      PI3K inhibitor LY294002 (0-60 micromol/L) for 8 days, and cellular growth was
      measured. Further, TT cells were treated with nontoxic concentrations of LY294002
      for 2 days, and Western blot analyses were performed for phospho-Akt, total Akt,
      and the NE tumor markers CgA and human achaete-scute homolog1 (ASCL1). RESULTS:
      Treatment of TT cells with LY294002 significantly suppressed levels of phospho
      Akt. Notably, a dose-dependent reduction in cellular proliferation was also
      observed. Importantly, NE marker production was also reduced. Mechanistically, we
      show that cell growth inhibition by PI3K inactivation is mediated by apoptosis
      attributable to an increase in the levels of cleaved poly(ADP-ribose) polymerase
      and caspase-3. CONCLUSIONS: MTC cell growth and NE marker production appear to
      depend on activation of the PI3K-signaling cascade. Inhibition of this important
      signal transduction pathway may lead to a possible therapeutic strategy to treat
      patients with MTC.

PMID- 17188152
TI  - Parathyroid hormone levels 4 hours after surgery do not accurately predict post
      thyroidectomy hypocalcemia.
AB  - BACKGROUND: We evaluated the reliability of intact parathyroid hormone (iPTH)
      levels 4 hours after thyroidectomy (4h-iPTH) as a predictor of hypocalcemia in a
      large series of patients. METHODS: A prospective experimental design involving
      523 consecutive patients between September 1, 2004, and June 30, 2005, was
      employed. The specificity, sensitivity, and overall accuracy of 4h-iPTH in
      predicting post-thyroidectomy hypocalcemia and symptoms were determined. RESULTS:
      A total of 199 patients developed hypocalcemia (serum calcium concentrations <8.0
      mg/dl). Five patients still were receiving vitamin D/oral calcium at 6 months
      after the operation. Seventy-three patients experienced mild symptoms. The 4h
      iPTH levels were reduced in hypocalcemic patients (28.8 +/- 15.3 vs 11.2 +/- 11.6
      pg/ml) (P < .001). The 4h-iPTH levels were within the normal range (10 to 65
      pg/ml) in 360 patients (290 normocalcemic) and subnormal in 163 patients (129
      hypocalcemic, of whom 62 were symptomatic). The accuracy of 4h-iPTH levels <10
      pg/ml in predicting post-thyroidectomy hypocalcemia and symptoms was 80.1% and
      78.6%, respectively. False-negative results were observed in 70 hypocalcemic
      patients (13.4%), 11 of whom were symptomatic (2.1%). CONCLUSIONS: Subnormal 4h
      iPTH levels alone did not accurately predict clinically relevant postoperative
      hypocalcemia. The optimal cut-off level and its integration with preoperative and
      postoperative serum calcium concentrations should be reconsidered.

PMID- 17188153
TI  - Voice and swallowing changes after thyroidectomy in patients without inferior
      laryngeal nerve injuries.
AB  - BACKGROUND: We performed a prospective analysis on voice and swallowing
      alterations following total thyroidectomy (TT), in the absence of recurrent nerve
      injury. METHODS: Patients aged 21 to 65 years undergoing TT, in the absence of
      laryngeal/pulmonary disease, previous neck surgery, or malignant diseases, were
      subjected to videostrobolaryngoscopy (VSL), acoustic voice analysis (AVA), and
      maximum phonation time (MPT) tests preoperatively and 3 months postoperatively.
      Voice impairment scores (VIS) and swallowing impairment scores (SIS) were
      obtained preoperatively, and at 1 week, 1 month, and 3 months postoperatively.
      RESULTS: Among the 127 selected patients, 39 completed the postoperative
      evaluation. No recurrent nerve injury was observed during the postoperative VSL
      in any of the patients. Preoperative and postoperative AVA and MPT scores did not
      differ significantly. The mean postoperative VIS was significantly higher than
      the preoperative VIS at 1 week and 1 month after TT (13.7 and 9.6 vs 4.4,
      respectively; P < .05) but not 3 months after TT (6.7). The mean SIS was higher
      than the preoperative SIS at 1 week, 1 month, and 3 months after TT (10.3, 6.0,
      and 2.8 vs 0.5, respectively; P < .05). CONCLUSIONS: Physicians should inform
      patients that transient voice and swallowing symptoms may occur following total
      thyroidectomy, and our data suggest mild symptoms may occur in the majority of
      operated patients.

PMID- 17188154
TI  - Thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has
      the highest sensitivity in monitoring differentiated thyroid carcinoma in
      children.

PMID- 17188155
TI  - Contralateral papillary thyroid cancer at completion thyroidectomy has no impact
      on recurrence or survival after radioiodine treatment.
AB  - BACKGROUND: This study investigated the rate of contralateral papillary thyroid
      cancer (PTC) in low-risk PTC patients who had completion thyroidectomy, and were
      referred for radioactive iodine (RAI) therapy. The study sought predictors of
      contralateral disease and examined the impact of contralateral disease in RAI
      treated patients. METHODS: We reviewed 20 years of data from a prospective
      registry for 150 patients with PTC. These patients had undergone thyroid
      lobectomy, followed by completion thyroidectomy, and had been referred for RAI.
      RESULTS: Of the 150 patients, 41% had PTC in the contralateral lobe. There was no
      difference in the rate of contralateral disease in low-risk patients (age <45
      years, T1 tumors, lymph node-negative) compared with the remainder. There were no
      significant differences between patients with or without contralateral disease
      with respect to primary tumor size, mean age, time to completion thyroidectomy,
      or metastatic lymph node disease. Logistic regression analyses showed no
      histologic parameters that correlated with contralateral disease. There were no
      recurrence or survival differences in patients with or without contralateral
      disease after resection and RAI. CONCLUSIONS: The prevalence of tumor in the
      contralateral lobe of low-risk patients with PTC is significant and warrants
      consideration for completion thyroidectomy and radioiodine treatment. Our
      results, however, suggest that contralateral disease does not have an impact on
      recurrence or survival after treatment.

PMID- 17188156
TI  - Lymph node metastases in differentiated thyroid cancer under 2 cm.
AB  - BACKGROUND: The goal of this study was to evaluate the presence of lymph node
      metastasis in patients with T1 differentiated thyroid cancer (DTC) and determine
      prognostic significance for tumor recurrence and cancer-related death. METHODS:
      From a prospective tumor registry, we reviewed data from 551 patients with DTC
      who underwent total or subtotal thyroidectomy and who had primary tumor size </=2
      cm. Patients received standard radioactive iodine ablation. RESULTS: The
      proportion of patients with lymph node metastasis was 45%. This percentage
      remained the same in a comparison of tumors from 0 to 1 cm with tumors from 1 to
      2 cm. Logistic regression analyses did not identify primary tumor size as a
      predictor of lymph node metastasis, but did show that histologic vascular
      invasion and soft tissue invasion correlated with positive lymph nodes.
      Multifocal disease approached significance. Actuarial estimates for first
      recurrence displayed a significant difference in patients who had positive
      cervical lymph nodes versus negative nodes: 56% versus 71% disease-free at 20
      years. There was no difference in cancer-related death. CONCLUSIONS: In T1 DTC,
      lymph node metastasis does not correlate with tumor size but does correlate with
      vascular/soft tissue invasion. Patients with positive lymph nodes have a higher
      recurrence risk, but no significant increase in death.

PMID- 17188157
TI  - Surgical management of Graves disease in childhood and adolescence: an
      institutional experience.
AB  - BACKGROUND: Graves disease is the most common cause of hyperthyroidism in
      children. Medical therapy, radioiodine ablation, and thyroidectomy are all
      treatment options. To evaluate the safety and efficacy of operative therapy, we
      updated our operative experience with pediatric Graves disease at a single
      tertiary care center. METHODS: The medical records of children <18 years old who
      underwent thyroidectomy for Graves disease between 1986-2003 were reviewed.
      RESULTS: We identified 78 patients (median age, 13.8 years; 87% female). The most
      common presenting signs and symptoms included heat intolerance (61%), decreased
      academic performance (50%), tremor (49%), and ophthalmopathy (43%). All patients
      had clinical and laboratory evidence of autoimmune thyrotoxicosis. Sixty-nine
      percent chose operative therapy because of failure of medical therapy or adverse
      drug reactions. Near-total thyroidectomy was the most common surgical procedure
      performed (65%). Pathology demonstrated previously unrecognized thyroid
      malignancies in 4 (5%) patients. Operative morbidities were transient and
      included hypoparathyroidism (6%) and recurrent laryngeal nerve neuropraxia (1%).
      Three (4%) patients who underwent subtotal thyroidectomy developed recurrent
      hyperthyroidism; all were treated successfully with radioiodine ablation. Of
      patients presenting with ophthalmopathy, 85% noted improvement postoperatively,
      while 1 (3%) patient experienced worsening of symptoms. Only 5% developed new
      onset Graves ophthalmopathy after operation. CONCLUSIONS: Near-total
      thyroidectomy for Graves disease in children is safe and effective when performed
      by experienced thyroid surgeons. In addition to relief of systemic symptoms, the
      majority of patients presenting with Graves ophthalmopathy experienced
      improvement of their ocular disease after operation. In 5% of patients, surgical
      management allowed for detection and treatment of clinically occult thyroid
      malignancies.

PMID- 17188158
TI  - A tale of three papers.

PMID- 17188161
TI  - Transforming growth factor-beta: what every pancreatic surgeon should know.

PMID- 17188162
TI  - Blood doping in the surgical intensive care unit: evidence-based surgical
      rebuttal.

PMID- 17188163
TI  - Meta-analysis of clinical outcome after first and second liver resection for
      colorectal metastases.
AB  - BACKGROUND: The perioperative risk and long-term survival benefit of repeat
      hepatectomy for patients with liver metastases from colorectal cancer, compared
      with that of a first liver resection, has been reported with varying results in
      the literature. METHODS: The literature was searched using Medline, Embase, Ovid,
      and Cochrane databases for all studies published from 1992 to 2006. Two authors
      independently extracted data using the following outcomes: postoperative
      complications and mortality; disease recurrence; and long-term survival. Trials
      were assessed using the modified Newcastle-Ottawa Score. Random-effect meta
      analytical techniques were used for analysis. RESULTS: Twenty-one studies met the
      inclusion criteria, comprising 3,741 patients. The use of adjuvant chemotherapy
      was similar in both groups (odds ratio [OR] = 0.97; 95% confidence interval [CI]
      = 0.54, 1.74; P = .92), as was the number of hepatic nodules present at the time
      of first or second resection (weighted mean difference [WMD] = 0.18; 95% CI = 
      0.22, 0.57; P = .380). Wedge resection was carried out less often at first
      hepatectomy (39% vs 46%; OR = 0.66; 95% CI = 0.44, 1.00; P = .05). There was
      significantly less blood loss in patients undergoing first versus second
      hepatectomy (WMD = 238 ml; 95% CI = 90, 385; P = .002). There was no difference
      in perioperative morbidity (OR = 1.01; 95% CI = 0.65, 1.55; P = .98), mortality
      (OR = 1.01; 95% CI = 0.18, 5.72; P = .99) or long-term survival (HR = 0.90; 95%
      CI = .66, 1.24; P = .530) between groups. CONCLUSIONS: Repeat hepatectomy for
      patients with colorectal cancer metastases is safe and provides survival benefit
      equal to that of a first liver resection.

PMID- 17188164
TI  - Toward optimal recording of surgical complications: concurrent tracking compared
      to the discharge data set.
AB  - BACKGROUND: Information extracted from the hospital discharge data set is used
      increasingly for outcomes research and for benchmarking hospital and provider
      performance. The accuracy of these data in detecting vascular complications has
      never been validated. METHODS: We compared morbidity and mortality data derived
      from the hospital discharge data set to similar data recorded concurrently by our
      Surgical Activity Tracking System (SATS) for 1 year on the vascular surgery
      service. RESULTS: Of 798 total admissions, no complications were detected by
      either system in 598 admissions (75%). In 200 admissions (25%), there were 335
      complications, including 24 deaths (3.0%), that occurred either in-hospital or
      within 30 days of the date of operation or the date of discharge for nonoperative
      admissions. Of the 335 complications, 180 (53.7%) were recorded by both systems;
      the SATS missed 59 complications recorded in the hospital discharge data set
      (17.6%), whereas the hospital discharge data set missed 96 complications recorded
      in the SATS (28.7%, P = .003). Of the 289 in-hospital complications, the SATS
      recorded 230 (79.5%), whereas the hospital discharge data set recorded 229
      (79.2%). Of the 24 deaths, the hospital discharge data set missed 6 that occurred
      after discharge but within the 30-day reporting period CONCLUSIONS: Both systems
      are not completely accurate for tracking inpatient complications. The SATS was
      more representative than the hospital discharge data set in capturing 30-day
      morbidity and mortality. An amalgamation of the 2 systems would provide more
      optimal tracking of complications.

PMID- 17188165
TI  - Splenectomy ameliorates acute multiple organ damage induced by liver warm
      ischemia reperfusion in rats.
AB  - BACKGROUND: Liver ischemia/reperfusion (I/R) results in the release of
      destructive proinflammatory cytokines and oxygen-derived radicals, which in turn
      cause injury to liver and other organs such as kidney, lung, and intestine.
      Splenectomy protects organs from intestinal I/R injury. Therefore, the present
      study aims to investigate whether splenectomy could also ameliorate multiple
      organ damage caused by liver I/R. METHODS: Wistar rats randomly assigned into 4
      groups underwent sham-operation, splenectomy, hepatic I/R induced by occlusion of
      hepatic artery and portal vein, and splenectomy plus hepatic I/R, respectively.
      Blood samples were collected for assessing aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) activity, and tumor necrosis factor-alpha (TNF
      alpha) levels. The activity of myeloperoxidase (MPO) in liver tissues was
      assessed. Livers, kidneys, lungs, and small intestines underwent histopathologic
      examination for scoring injury severity and TUNEL assay for cell apoptosis. The
      expression of caspase-3 was evaluated with Western blot analysis. RESULTS: Liver
      I/R resulted in liver injury as evidenced by morphologic abnormalities, increased
      serum activities of AST and ALT, and increased percentage of apoptotic cells. The
      activity of MPO in liver tissues and the serum levels of TNF-alpha were increased
      after I/R. Splenectomy significantly decreased the histologic severity score,
      apoptotic index, MPO activity, and serum levels of AST, ALT, and TNF-alpha.
      Hepatic I/R also caused damage to kidneys, lungs, and small intestines, as
      evaluated by histologic alterations and increased apoptotic cells; these changes
      were ameliorated by splenectomy. The expression of caspase-3 was upregulated in
      the 4 organs by hepatic I/R and inhibited by splenectomy. CONCLUSIONS:
      Splenectomy protects the liver as well as the kidney, lung, and intestine from
      injury by hepatic I/R. Although the mechanism needs further investigation, this
      study demonstrated that splenectomy inhibited leukocyte infiltration in livers,
      release of TNF-alpha, cell apoptosis, and expression of caspase-3.

PMID- 17188167
TI  - Simple scoring system for the prediction of the prognosis of severe acute
      pancreatitis.
AB  - BACKGROUND: In severe acute pancreatitis (SAP), it is important clinically to
      predict the prognosis at the time of admission. Most scoring systems for severity
      of acute pancreatitis consist of multiple factors and are complicated. This
      investigation aimed to propose a simple scoring system for the prediction of the
      prognosis of SAP. METHODS: Prognostic factors were evaluated by receiver operator
      characteristic curve analyses and multivariate analysis from data that were
      obtained on admission of 137 patients with SAP. A simple scoring system with 3
      most useful factors was made, and its usefulness was investigated in comparison
      with conventional scoring systems. RESULTS: Three prognostic factors were
      selected: serum blood urea nitrogen > or = 25 mg/dL, serum lactate dehydrogenase
      > or = 900 IU/L, and contrast-enhanced computed tomography finding with
      pancreatic necrosis. On admission, 137 patients were classified from 0 to 3 by
      the number of positive items (simple prognostic score [SPS]). Mortality rates for
      patients whose SPS was 0, 1, 2, and 3 were 2% (1/42 patients), 18% (7/40
      patients), 48% (12/25 patients), and 67% (20/30 patients), respectively.
      Furthermore, when usefulness of SPS was compared with conventional scoring
      systems, the area under the curve by receiver operator characteristic curve
      analyses in SPS was 0.83; the Ranson score was 0.83; the Japanese severity score
      was 0.83; the Acute Physiology and Chronic Health Evaluation II score was 0.81,
      and the Glasgow score was 0.75. After onset, SPS kept almost same levels from day
      2 to day 6, and a significant difference was observed between survivors and
      nonsurvivors from day 1 to day 6. CONCLUSION: This scoring system that comprised
      3 items is simple, is feasible for the prediction of prognosis and conventional
      scoring systems, and is useful for the selection of the extremely severe patients
      with SAP on admission.

PMID- 17188168
TI  - Identification of severe acute pancreatitis using an artificial neural network.
AB  - BACKGROUND: The aim of this study was to construct and validate an artificial
      neural network (ANN) model to identify severe acute pancreatitis (AP) and predict
      fatal outcome. METHODS: All patients who presented with AP from January 2000 to
      September 2004 were reviewed. Presentation data on admission and at 48 hours were
      collected. Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow
      severity (GS) score were calculated. A feed-forward ANN was created and trained
      to predict development of severe AP and mortality from AP; 25% of the data set
      was withheld from training and was used to evaluate the accuracy of the ANN.
      Accuracy of the ANN in predicting severity of AP was compared with APACHE II and
      GS scores. RESULTS: A total of 664 patients with AP were identified of whom 181
      (27.3%) fulfilled the clinical and radiologic criteria for severe pancreatitis
      and 42 patients died (6.3%). Median APACHE II score at 48 hours was 4 (range, 0
      to 23). ANN was more accurate than APACHE II or GS scoring systems at predicting
      progression to a severe course (P < .05 and P < .01, respectively), predicting
      development of multiorgan dysfunction syndrome (P < .05 and P < .01) and at
      predicting death from AP (P < .05). CONCLUSIONS: An ANN was able to predict
      progression to severe disease, development of organ failure and mortality from
      acute pancreatitis with considerable accuracy and outperformed other clinical
      risk scoring systems. Further studies are required to assess its utility in
      aiding management decisions in patients with AP.

PMID- 17188166
TI  - Expression and prognostic significance of prothymosin-alpha and ERp57 in human
      gastric cancer.
AB  - PURPOSE: Prothymosin-alpha and ERp57 were previously identified as markers for
      gastric metaplasia in a mouse model of Helicobacter-induced gastric metaplasia
      and neoplasia. In this paper we assess whether the expression of these putative
      biomarkers in humans is correlated with gastric metaplasia and adenocarcinoma and
      clinical outcomes. METHODS: Eight tissue microarrays, containing 749 paraffin
      embedded tissue cores from 164 gastric cancer patients, were stained for
      prothymosin-alpha and ERp57 by horseradish peroxidase immunohistochemical
      techniques. The proportion of stained cells per core was quantitated using the
      Ariol SL-50 automated image analysis system. RESULTS: Prothymosin-alpha stained a
      significantly higher percentage of nuclei in cancer and metastases compared with
      normal gastric mucosa. ERp57 staining was significantly decreased in cancer and
      metastases compared with both normal gastric mucosa and metaplasias. ERp57
      expression also correlated with greater depth of tumor invasion and advanced
      stage of disease. Kaplan-Meier survival analysis determined that tumors with the
      highest quartile of ERp57 expression were statistically associated with longer
      postoperative survival. A Cox proportional hazard analysis showed that
      maintenance of ERp57 expression was associated with longer postoperative
      survival. CONCLUSIONS: These results suggest that although prothymosin-alpha is
      overexpressed in gastric adenocarcinoma, it is not associated with alterations in
      survival. In contrast, loss of ERp57 expression correlated with more aggressive
      disease and could provide useful prognostic information for gastric cancer
      patients.

PMID- 17188170
TI  - Cervical spine fracture patterns mandating screening to rule out blunt
      cerebrovascular injury.
AB  - BACKGROUND: Aggressive screening for blunt cerebrovascular injury (BCVI) and
      prompt anticoagulation for documented injuries has resulted in a significant
      reduction in ischemic neurologic events. An association between vertebral artery
      injuries (VAIs) and specific cervical spine fracture patterns has been suggested;
      however, current screening guidelines would subject all patients with cervical
      spine fractures to imaging because no distinction has been made for carotid
      artery injuries (CAIs). We hypothesized that specific cervical spine fracture
      patterns that warrant screening evaluation exist, hence limiting unwarranted
      diagnostic imaging. METHODS: Patients undergoing screening for BCVI on the basis
      of injury patterns and mechanism have been prospectively followed at our regional
      trauma center since January 1996. RESULTS: During the study period from January
      1996 to January 2005, there were 17,007 blunt trauma admissions. Twenty-three
      patients presented with symptoms of BCVI. Screening angiography was performed in
      766 patients (4.5%), and diagnosed 258 (34%) patients with BCVI. One hundred
      twenty-five patients with BCVI had cervical spine fractures; 18 patients had
      isolated CAI; 84 had isolated VAI, and 23 had combined CAI and VAI. Eight
      patients with VAI had minor cervical fractures but underwent screening for other
      injury patterns. Fractures in the remaining patients with BCVI were 1 of 3
      patterns. Subluxations in 56 (48%) patients, C1 to C3 cervical spine fractures in
      42 (36%), or extension of the fracture through the foramen transversarium in 19
      (16%). Cervical spine fractures were the sole indication for screening in 90% of
      the study population. Screening yield of all patients admitted with 1 of these 3
      fracture patterns was 37%. CONCLUSIONS: Blunt cerebrovascular injury is
      associated with complex cervical spine fractures that include subluxation,
      extension into the foramen transversarium, or upper C1 to C3 fractures. Patients
      sustaining such cervical fractures should undergo prompt screening.

PMID- 17188169
TI  - Characteristics of recurrence and surveillance tools after curative resection for
      colorectal cancer: a multicenter study.
AB  - BACKGROUND: The aim of this study was to clarify the characteristics of
      recurrence and the effectiveness of surveillance tools after curative resection
      for colorectal cancer. METHODS: We enrolled 5230 consecutive patients (stage I,
      1367; stage II, 1912; stage III, 1951) who underwent curative resection at 14
      hospitals from 1991 to 1996. All patients were followed up intensively, and their
      outcomes were investigated retrospectively. RESULTS: Of the 5230 patients, 906
      developed recurrence. The recurrence rates of stage I, II, and III cancers were
      3.7%, 13.3%, and 30.8%, respectively (P < .0001). The curves of the cumulative
      appearance rate of recurrence in stage II and III patients showed a rapid
      increase for the first 3 years. Recurrence after 5 years was less than 1% in each
      stage. Clinical visits combined with measurements of tumor markers detected the
      majority of recurrences except in the case of lung metastasis. In contrast, 43.4%
      of hepatic recurrences were detected by liver imaging, and 48.4% of pulmonary
      recurrences were noted by chest x-ray. The 5-year survival rates after primary
      colorectal surgery in patients who underwent resection for recurrence were better
      than in those without resection: 55% vs 11% in hepatic recurrence, 68% vs 13% in
      pulmonary recurrence, and 48% vs 22% in local recurrence (all P < .001).
      CONCLUSION: It is useful to take these characteristics of recurrence into account
      in the management of patients after curative resection for colorectal cancer and
      in the setting of clinical trial for follow-up after curative resection for
      colorectal cancer.

PMID- 17188171
TI  - Inflammatory abdominal aortic aneurysm: predictors of long-term outcome in a case
      control study.
AB  - BACKGROUND: Inflammatory abdominal aortic aneurysms (AAAs) are relatively rare
      clinical entities. The aim of this study is to ascertain the risk factors in
      patients with inflammatory AAAs and clarify which feature plays a role in
      determining the long-term outcome in these patients. METHODS: Between 1990 and
      1997, 238 patients underwent surgery for an AAA at our institution, 17 (7.1%) of
      whom had the diagnosis of inflammatory type AAA. This group was matched in a case
      control fashion to a group of 35 patients with similar characteristics of age,
      gender, and preoperative risk factors who were operated on for a noninflammatory
      AAA. All available clinical, pathologic, and postoperative variables were
      retrospectively reviewed, and the 2 groups were compared. In the inflammatory
      group, risk factor analysis was performed for poor outcome. RESULTS: All
      operations were performed through a standard transperitoneal median laparotomy.
      The 2 groups did not differ significantly in terms of clinical characteristics
      and preoperative risk factors Patients with inflammatory AAAs were significantly
      more symptomatic (100% vs 31%, P = .03) and had larger aneurysm size on admission
      (8.2 +/- 1.2 cm vs 6.1 +/- 0.4 cm, P = .04). In inflammatory AAAs, preoperative
      erythrocyte sedimentation rate was found to be significantly elevated (mean, 48
      +/- 14 mm/h vs 8 +/- 3 mm/h, P = .01). Surgical morbidity and mortality rates did
      not differ between 2 groups. The intensive care unit and hospital stay periods
      were similar in both groups (2.2 days vs 1.8 days, P = .25, and 9.2 days vs 8.1
      days, P = .35). Eight-year survival rates of inflammatory and noninflammatory
      groups were 60% and 74%, respectively (P = .01). Results from Cox proportional
      hazards model analysis showed that a high sedimentation rate after surgical
      intervention (P = .02), cardiovascular disease (P = .01), postoperative
      persisting fibrosis with ureteral entrapment (P = .01), and postoperative chronic
      renal failure (P = .02) were independent risk factors for death. Other surgical
      variables did not prove to be risk factors for long-term mortality. CONCLUSIONS:
      Although the preoperative characteristics may differ in patients with
      inflammatory type AAAs, they can be treated today with low morbidity and
      mortality rates. However, inflammatory process may continue postoperatively
      because of unknown reasons, and the study documented that persisting,
      postoperative inflammatory process with or without retroperitoneal fibrosis may
      place a patient at high risk for poor outcome. This is important information for
      the long-term management of these patients, and we believe that their follow-up
      protocols should be more comprehensive to further improve their long-term
      survival rates.

PMID- 17188173
TI  - Invited commentary: medullary thyroid cancer: the importance of RET testing.

PMID- 17188172
TI  - Mutation analysis of the RET proto-oncogene and early thyroidectomy: results of a
      Portuguese cancer centre.
AB  - BACKGROUND: Evidence that germline mutations in the RET proto-oncogene are the
      underlying cause of the familial form of medullary thyroid carcinoma (MTC) made
      it possible to identify gene carriers with a very high degree of accuracy. Aiming
      to define the mutational profile observed in our patients and to assess gene
      carriers' compliance with an early surgery, we reviewed results of molecular
      analysis of RET performed at our institution since 1994. METHODS: One hundred
      fifty-eight individuals were screened for germline mutations of the RET proto
      oncogene. Seventy-seven patients had apparently sporadic MTC; 8 patients had both
      MTC and pheochromocytoma or MTC and clinical features of multiple endocrine
      neoplasia type 2B despite a negative family history; 8 patients were known to
      belong to affected kindreds; and 65 individuals were at-risk individuals to
      develop MTC. RESULTS: A germline mutation in RET was identified in 4% of
      apparently sporadic MTC patients, in 100% of patients with MTC and
      pheochromocytoma or MTC and clinical features of multiple endocrine neoplasia
      type 2B, and in 100% of probands of clinically established kindreds. The most
      affected codon was 634 (58%) followed by codon 804 (16%). Among at-risk
      individuals, 49% were identified as gene carriers. Seven individuals were
      submitted to prophylactic thyroidectomy (mean age, 17.7 +/- 12.5 years; range: 3
      42 years), and all but 1 had MTC. CONCLUSIONS: RET mutational spectrum observed
      in the present population disclosed a higher frequency of codon 804 mutations
      than expected. Compliance with an early prophylactic surgery seemed to be
      influenced not only by medical advice and cultural factors but also by the
      aggressiveness of disease in gene carriers' families.

PMID- 17188174
TI  - Exploring quality of life for patients undergoing major surgery: the perspectives
      of surgeons, other healthcare professionals, and patients.
AB  - BACKGROUND: Surgeons, other healthcare professionals, and patients may identify
      different health-related concerns related to the quality of life of patients
      undergoing major surgery. METHODS: Semistructured interviews were conducted with
      surgeons (n =14), other healthcare professionals (n =19), and patients undergoing
      major elective surgery (n = 52). Themes were extracted by content analysis and
      organized into major domains. The frequencies with which specific themes were
      mentioned were compared among groups. RESULTS: A total of 85 themes were
      extracted from the interviews, 15 of which were mentioned by 50% or more of
      participants in each group, representing 5 of the 6 domains. The greatest
      differences were observed in the domains of social well-being, wherein 5 themes
      were mentioned less often by surgeons than other groups, and spiritual well
      being, wherein 2 themes were mentioned more often by patients than other groups.
      Differences in the physical, emotional, cognitive preparation, and concern about
      quality of care domains were minimal. CONCLUSIONS: Surgeons, other healthcare
      professionals, and patients identified many similar concerns related to the well
      being of patients undergoing major surgery. However, the importance of social and
      spiritual themes to patients may be underestimated by surgeons.

PMID- 17188175
TI  - Community-acquired methicillin-resistant Staphylococcus aureus liver abscess
      requiring resection.

PMID- 17188176
TI  - Isolated total caval clamping with "preserved remnant liver perfusion" for
      combined hepatic and venacaval resection in tumors involving venacava.

PMID- 17188177
TI  - Chester B. McVay: small-town surgeon, world-famous herniologist.

PMID- 17188179
TI  - Demonstration of the common hepatic artery coursing in the lesser omentum by
      three-dimensional computed tomography.

PMID- 17188178
TI  - Preoperative evaluation of thyroid nodules with 18FDG-PET/CT or MIBI scan?

PMID- 17188180
TI  - Capsule endoscopy: a note of caution.

PMID- 17188181
TI  - Plasma large Tenascin-C spliced variant as a possible biomarker for the
      prediction of hepatic recurrence in colorectal cancer.

PMID- 17188182
TI  - The HATM and HRTM: their future together.

PMID- 17188183
TI  - Human alimentary tract model for radiological protection. ICRP Publication 100. A
      report of The International Commission on Radiological Protection.
AB  - In this report, the ICRP provides a new biokinetic and dosimetric model of the
      human alimentary tract to replace the Publication 30 (ICRP, 1979) model. The new
      human alimentary tract model (HATM) will be used together with the human
      respiratory tract model (HRTM; ICRP, 1994a,b) in future ICRP publications on
      doses from ingested and inhaled radionuclides. The HATM is applicable to all
      situations of radionuclide intake by children and adults. It provides age
      dependent parameter values for the dimensions of the alimentary tract regions,
      and associated transit times for the movement of materials through these regions.
      For adults, gender-dependent parameter values are given for dimensions and
      transit times. The default assumption is that radionuclide absorption takes place
      in the small intestine, but the model allows for absorption in other regions and
      for retention in or on tissues within the alimentary tract when information is
      available. Doses are calculated to target cells for cancer induction in the oral
      cavity, oesophagus, stomach, small intestine, and colon. This report provides
      reviews of information on the transit of materials through the alimentary tract
      and on radionuclide retention and absorption. It considers data on health
      effects, principally in order to specify the target cells for cancer induction
      within the mucosal lining of the tract and to justify approaches taken to dose
      averaging within regions. Comparisons are made between doses calculated using the
      HATM and the Publication 30 model for examples of radionuclide ingestion for
      which absorption is assumed to occur in the small intestine alone. Examples are
      also given of the effects on doses of considering absorption from other regions
      and the effect of possible retention in the alimentary tract. This report also
      considers uncertainties in model assumptions and their effect on doses, including
      alimentary tract dimensions, transit times, radionuclide absorption values, and
      the location of targets for cancer induction.

PMID- 17188198
TI  - Ochratoxin degradation and adsorption caused by astaxanthin-producing yeasts.
AB  - Ochratoxin degrading and adsorbing activities of Phaffia rhodozyma and
      Xanthophyllomyces dendrorhous isolates were tested. P. rhodozyma CBS 5905
      degraded more than 90% of ochratoxin A (OTA) in 15 days at 20 degrees C. The data
      presented indicate that P. rhodozyma is able to convert OTA to ochratoxin alpha,
      and this conversion is possibly mediated by an enzyme related to
      carboxypeptidases. Chelating agents like EDTA and 1,10-phenanthroline inhibited
      OTA degradation caused by P. rhodozyma indicating that the carboxypeptidase is a
      metalloprotease, similarly to carboxypeptidase A. The temperature optimum of this
      enzyme was found to be above 30 degrees C, which is much higher than the
      temperature optimum for growth of P. rhodozyma cells, which is around 20 degrees
      C. The enzyme responsible for ochratoxin degradation was found to be cell-bound.
      Besides, both viable and heat-treated (dead) P. rhodozyma cells were also able to
      adsorb significant amounts (up to 250 ng ml(-1)) of OTA. Heat treatment enhanced
      OTA adsorbing activities of the cells. Further studies are in progress to
      identify the enzyme responsible for OTA degradation in P. rhodozyma.

PMID- 17188197
TI  - Use of linear, Weibull, and log-logistic functions to model pressure inactivation
      of seven foodborne pathogens in milk.
AB  - Survival curves of six foodborne pathogens suspended in ultra high-temperature
      (UHT) whole milk and exposed to high hydrostatic pressure at 21.5 degrees C were
      obtained. Vibrio parahaemolyticus was treated at 300 MPa and other pathogens,
      Listeria monocytogenes, Escherichia coli O157:H7, Salmonella enterica serovar
      Enteritidis, Salmonella enterica serovar Typhimurium, and Staphylococcus aureus
      were treated at 600 MPa. All the survival curves showed a rapid initial drop in
      bacterial counts followed by tailing caused by a diminishing inactivation rate. A
      linear model and two nonlinear models were fitted to these data and the
      performances of these models were compared using mean square error (MSE) values.
      The log-logistic and Weibull models consistently produced better fits to the
      inactivation data than the linear model. The mean MSE value of the linear model
      was 6.1, while the mean MSE values were 0.7 for the Weibull model and 0.3 for the
      log-logistic model. There was no correlation between pressure resistance and the
      taxonomic group the bacteria belong to. The order, most to least pressure
      sensitive, of the single strains tested was: V. parahaemolyticus (gram
      negative)<L. monocytogenes (gram positive)<Salmonella Typhimurium (gram negative)
      approximately = Salmonella Enteritidis (gram negative)<E. coli O157:H7
      approximately = Staphylocollus aureus (gram positive)<Shigella flexneri (gram
      negative). The most pressure-resistant gram-negative bacterium, Shigella
      flexneri, and most pressure resistant gram-positive bacterium, Staphylocollus
      aureus, were pressurized at 50 degrees C. Staphylocollus aureus was treated at
      500 MPa and Shigella flexneri at 600 MPa. Elevated temperature considerably
      enhanced pressure inactivation of these two pathogens, but did not affect the
      overall shape of the survival curves. Pressure level (250 MPa) and substrate (1%
      peptone water plus 3% NaCl) in which V. parahaemolyticus was suspended affected
      the shape of survival curves of V. parahaemolyticus.

PMID- 17188199
TI  - Growth of Listeria monocytogenes in egg salad and pasta salad formulated with
      mayonnaise of various pH and stored at refrigerated and abuse temperatures.
AB  - This study investigated and modeled the behavior of Listeria monocytogenes in egg
      salad and pasta salad as affected by mayonnaise pH (3.8, 4.2, 4.6, and 5.0) and
      storage temperature (4, 8, and 12 degrees C). At each storage temperature, L.
      monocytogenes was able to grow in both salads regardless of the mayonnaise pH.
      The lag-phase durations (LPD) of L. monocytogenes in egg salad ranged from 33 to
      85, 15 to 50, and 0 to 19 h, and the growth rates (GR) ranged from 0.0187 to
      0.0318, 0.0387 to 0.0512, and 0.0694 to 0.1003 log(10)cfu/h at 4, 8, and 12
      degrees C, respectively. The LPD of L. monocytogenes in pasta salad ranged from
      210 to 430, 49 to 131, and 21 to 103 h, and GR ranged from 0.0118 to 0.0350,
      0.0153 to 0.0418, and 0.0453 to 0.0718 log(10)cfu/h at 4, 8, and 12 degrees C,
      respectively. The growth of L. monocytogenes was more rapid in egg salad than in
      pasta salad, indicating that a better growth environment for L. monocytogenes
      existed in egg salad. In both salads, the LPD decreased and the GR increased as
      the storage temperature increased. Mathematical models and response surface plots
      describing the LPD and GR of L. monocytogenes in both salads as affected by the
      mayonnaise pH and storage temperature were developed. The models confirmed that
      the growth of L. monocytogenes in egg salad and pasta salad was primarily
      promoted by higher storage temperatures and, secondarily, by higher mayonnaise
      pH. The conditions under which the models may be applied to estimate the growth
      of L. monocytogenes in both salads were identified.

PMID- 17188200
TI  - Prevalence of Campylobacter species in meat, milk and other food commodities in
      Pakistan.
AB  - A surveillance study was carried out to determine the prevalence of Campylobacter
      in meat, milk and other food commodities in Pakistan. Over a period of 3 years
      (January 2002-December 2004), a total of 1636 food samples of meat, milk and
      other food commodities were procured from three big cities of Pakistan
      (Faisalabad, Lahore and Islamabad) and were analysed. Among meat samples, the
      highest prevalence (48%) of Campylobacter was recorded in raw chicken meat
      followed by raw beef (10.9%) and raw mutton (5.1%). Among other food commodities,
      the highest prevalence was observed in vegetable/fruit salad (40.9%), sandwiches
      (32%), cheese (11%) and raw bulk milk samples (10.2%). The overall prevalence of
      Campylobacter was found to be 21.5%, out of which 70.6% were identified as
      Campylobacter (C.) jejuni and 29.4% as C. coli. The study reported that the
      prevalence of Campylobacter spp. was significantly higher in the food
      commodities, which included raw/undercooked ingredients.

PMID- 17188201
TI  - Reduction of Escherichia coli population following treatment with bacteriocins
      from lactic acid bacteria and chelators.
AB  - The inhibitory activity of lactocin 705/AL705 (2133 arbitrary units per ml (AU
      ml(-1))), two bacteriocins produced by Lactobacillus curvatus CRL705 and nisin
      (1066AU ml(-1)) produced by Lactococcus lactis CRL1109 in combination with
      chelating agents against Escherichia coli strains in TSB medium at 21 and 6
      degrees C was investigated. Treatment with EDTA (500 and 1000 mm) and Na lactate
      (800 mm) alone produced a variable effect depending on the strain, Na lactate
      being inhibitory against E. coli NCTC12900 at both assayed temperatures while
      EDTA (1000 mm) led to its inactivation only at 6 degrees C. Direct and deferred
      strategies using EDTA and Na lactate showed that the direct addition of
      bacteriocins and chelators was not as effective as compared to deferred
      treatments. When the deferred treatment effectiveness was evaluated at 6 degrees
      C, the use of EDTA (500 and 1000 mm) and Na lactate (800 mm) in combination with
      lactocin 705/AL705 demonstrated to be the most inhibitory strategy against both
      E. coli strains. Nevertheless, treatments with chelators and bacteriocins was
      highly dependent upon strain sensitivity. Permeabilization of the outer membrane
      of E. coli strains with EDTA and Na lactate combined with lactocin 705/AL705
      showed to be valuable in controlling this foodborne bacteria at low temperatures.

PMID- 17188202
TI  - A critical review of measurement uncertainty in the enumeration of food micro
      organisms.
AB  - Derivation of uncertainty provides a way to standardize the expression of
      variability associated with any analytical procedure. The published information
      on uncertainty associated with data obtained using microbiological procedures is
      reviewed to highlight the causes and magnitude of such variability in food
      microbiology. We also suggest statistical procedures that can be used to assess
      variability (and hence, uncertainty), within and between laboratories, including
      procedures that can be used routinely by microbiologists examining foods, and the
      use of 'robust' methods which allow the retention of 'outlying' data. Although
      concerned primarily with variability associated with colony count procedures, we
      discuss also the causes of variability in presence/absence and indirect methods,
      such as limiting dilution, most probable number and modern instrumental methods
      of microbiological examination. Recommendations are also made concerning the most
      important precautions to be taken in order to minimize uncertainty in
      microbiology. These include strict internal controls at all stages of
      microbiological testing, as well as validation of methods, trend analysis, use of
      reference materials and participation in proficiency testing schemes. It is
      emphasized that the distribution of microbes in foods is inherently
      heterogeneous, and that this review only addresses uncertainty of measurement
      with respect to the sample taken, not the lot or consignment of food from which
      the sample was taken.

PMID- 17188203
TI  - Effect of intra and interspecific interaction on OTA production by A. section
      Nigri in grapes during dehydration.
AB  - The aim of this study was to assess the colonizing capability and OTA production
      of different populations of Aspergillus section Nigri spp. in grapes, as affected
      by the interactions with other fungi, during a simulated in vitro sun-drying.
      Mature white grapes were divided into two lots of healthy and artificially
      injured grapes and inoculated with A. section Nigri spp. (A. carbonarius OTA
      producer, A. niger aggregate OTA producer, A. niger aggregate OTA non-producer),
      Eurotium amstelodami and Penicillium janthinellum, in different combinations. The
      drying process was simulated adjusting water activity firstly at 0.98 a(w) and
      gradually decreasing it to 0.76 a(w) for a total of 20 days. Colonizing grape
      percentages were recorded after 5, 10, 15 and 20 days of dehydration and OTA
      content was measured after 5, 7, 10, 12, 15, 17 and 20 days. Colonization of
      grapes increased with time in all treatments. A. niger aggregate OTA-positive
      showed the highest colonization percentage, followed by A. carbonarius, and
      finally their mixed inoculum. When the two OTA-producing strains were combined,
      addition of any other microorganism increased the percentage of infection by A.
      section Nigri. A. carbonarius was the highest OTA producer in pure culture,
      followed by A. niger aggregate OTA-positive. In general, when competing fungi
      were added to A. carbonarius inoculum, the OTA content was reduced. E.
      amstelodami was the only competing fungus which increased OTA accumulation. The
      sun-drying process may be conducive to OTA accumulation in dried grapes. The
      complex fungal interactions which may take place during this process, may act as
      an additional control factor, given that the higher presence of A. niger
      aggregate OTA-negative inhibits OTA accumulation by OTA producing species.

PMID- 17188204
TI  - Phenotypic and technological diversity of lactic acid bacteria and staphylococci
      isolated from traditionally fermented sausages in southern Greece.
AB  - The physicochemical and microbiological characteristics of spontaneously
      fermented sausages made by two medium-sized enterprises (MSE) located in southern
      Greece have been studied. A total of 300 lactic acid bacteria and 300
      staphylococcal strains have been isolated and identified by their physiological
      characteristics. Lactobacillus plantarum strains were found to dominate the
      lactic acid bacteria microbiota in most of the cases with L. sakei strains
      prevailing in some of them and L. rhamnosus strains occasionally accompanying the
      dominant lactic acid bacteria microbiota. On the other hand, S. saprophyticus
      strains were found to dominate the staphylococcal microbiota in all spontaneously
      fermented sausages with of S. simulans, S. xylosus, S. gallinarum and S. cohnii
      cohnii strains being sporadically present. Following the identification, an
      evaluation of their technological properties, namely proteolytic and lipolytic
      capacities as well as production of biogenic amines and antimicrobial compounds,
      took place. None of the lactic acid bacteria and staphylococci was found to
      possess lipolytic activity whereas a total of 6 lactic acid bacteria and 51
      staphylococci strains were found to be able to hydrolyse either the sarcoplasic,
      myofibrillar or both protein fractions. Furthermore, only one L. sakei strain and
      185 staphylococci strains were found to possess decarboxylase activity against
      lysine, tyrosine, ornithine or histidine. Finally none of the staphylococcal
      microbiota and 3 lactic acid bacteria strains were found to be able to produce
      antimicrobial compounds of proteinaceous nature against Listeria monocytogenes.

PMID- 17188205
TI  - Fungal strains isolated from cork stoppers and the formation of 2,4,6
      trichloroanisole involved in the cork taint of wine.
AB  - Cork taint is mainly due to 2,4,6-trichloroanisole (TCA) produced through the
      activity of undesirable fungal strains. We observed that CFU mould number in TCA
      containing stoppers was not quantitatively different to that of the stoppers not
      containing TCA (ca. 10(5)CFU/g). In contrast more fungi diversity was observed in
      TCA-containing stoppers. Penicillium spp (Penicillium chrysogenum, Penicillium
      glabrum), Aspergillus spp (Aspergillus niger and Aspergillus oryzae), Chrysonilia
      sitophila, Mucor racemosus, Paecilomyces sp. and Trichoderma viride were found in
      TCA-containing stoppers, while C. sitophila and Penicillium sp. were the main
      fungi in the stoppers devoid of TCA. Conidia were numerous close to the lenticels
      and present from the lateral surface through to the centre of the stoppers.
      Strains of Aspergillus, Mucor, Paecilomyces, Penicillium and Trichoderma isolated
      from TCA-containing stoppers were able to convert 2,4,6-trichlorophenol (TCP) in
      TCA in resting cell or growing conditions. The best yields of conversion were
      obtained by green fungi Paecilomyces sp. and P. chrysogenum, 17% and 20%,
      respectively. Chysonilia sitophila and Penicillium sp. did not produce TCA from
      TCP in our conditions.

PMID- 17188206
TI  - Effect of industrial and natural biocides on spoilage, pathogenic and
      technological strains grown in biofilm.
AB  - This study aimed at investigating bactericide solutions effective on spoilage and
      pathogenic bacteria while preserving technological bacteria. Two compounds of
      essential oil (thymol and eugenol), one essential oil of Satureja thymbra and two
      industrial biocides (PE 270-30, Brillo) were tested on technological strains
      (Staphylococcus equorum, Staphylococcus succinus and Lactobacillus sakei) grown
      in monoculture biofilm and on a mixed biofilm of pathogenic bacteria
      (Staphylococcus aureus, Listeria monocytogenes) and spoilage bacteria
      (Pseudomonas fragi, Escherichia coli). Biofilm cultures were performed in glass
      fibre filters for 24h at 20 degrees C before application of biocides. Thymol and
      eugenol had no effect on the mixed biofilm. S. thymbra (2%) was highly effective
      on spoilage strains (5 log reduction), and S. equorum (4 log reduction) was
      moderately effective on pathogens (2.3 log reduction) and not effective on S.
      succinus and L. sakei (0.5 log reduction). PE-270-30 with 10% Na((2))SO((4))
      decreased spoilage bacteria (5.1 log reduction), maintained the technological
      bacteria, but did not reduce the pathogens. The disinfectant Brillo (3%) killed
      all the strains. These results showed the difficulty in obtaining a biocide that
      is effective in destroying spoilage and pathogenic bacteria while preserving
      technological bacteria. Essential oils could be a good alternative for
      eradicating spoilage bacteria in the food environment where they are often found
      at high levels.

PMID- 17188207
TI  - Effect of time before storage and storage temperature on survival of Salmonella
      inoculated on fresh-cut melons.
AB  - The effects of a waiting period at room temperature ( approximately 22 degrees C)
      before refrigerating fresh-cut watermelon, cantaloupe and honeydew pieces
      contaminated with Salmonella on survival of the inoculated pathogen were
      investigated. Whole cantaloupes, honeydew melons and watermelons were washed with
      water, and fresh-cut pieces from individual melons were prepared and inoculated
      with a five strain cocktail of Salmonella at 10(5)cfu/ml. Populations of aerobic
      mesophilic bacteria, yeast and mold and Pseudomonas spp. were higher for fresh
      cut cantaloupe than for fresh-cut watermelon and honeydew immediately after
      preparation. Populations of Salmonella, aerobic mesophilic bacteria, yeast and
      mold and Pseudomonas ssp. in fresh-cut melons left at room temperature for up to
      5h before refrigeration were significantly (P<0.05) higher than populations in
      fresh-cut melons stored at 5 degrees C immediately after preparation. Populations
      of Salmonella recovered in fresh-cut melon after inoculation with the cocktail of
      Salmonella strains averaged 2 log(10)cfu/g for all three types of melons.
      Populations in fresh-cut watermelon and honeydew pieces declined by 1 log when
      stored immediately at 5 degrees C for 12 days, while the populations in fresh-cut
      cantaloupe did not show significant (P>0.05) changes. Populations of Salmonella
      in fresh-cut melons stored immediately at 10 degrees C for 12 days increased
      significantly (P<0.05) from 2.0 to 3.0 log(10)cfu/g in watermelon, 1.9 to 3.0
      log(10)cfu/g in honeydew and 2.0 to 3.6 log(10)cfu/g in cantaloupe pieces.
      Holding freshly prepared, contaminated fresh-cut melon pieces at 22 degrees C for
      3h or more prior to refrigerated storage would increase the chances of Salmonella
      proliferation, especially if the fresh-cut melons were subsequently stored at an
      abusive temperature.

PMID- 17188208
TI  - Survival of Helicobacter pylori in artificially contaminated ultrahigh
      temperature and pasteurized milk.
AB  - Helicobacter pylori (H. pylori) is a very important bacterial pathogen of humans
      which may cause gastrointestinal illnesses ranging from gastric and duodenal
      ulcers to neoplastic diseases such as MALToma and gastric cancer. Transmission
      via contaminated food is still uncertain but several authors believe this can
      realistically occur and milk may act as a vehicle of infection. This paper
      reports the results of H. pylori survival trials in pasteurized and ultrahigh
      temperature (UHT) milks artificially contaminated and aerobically stored at 4
      degrees C. The results obtained showed that the four strains used in this study
      (H. pylori nat 18-19-20 and H. pylori ATCC 43504), had a progressive reduction in
      bacterial load with a median survival of 9 days in pasteurized milk and 12 days
      in UHT milk, with approximate average of initial inoculum of 10(5) and
      10(6)cfu/ml, respectively. These findings are very important to clarify the route
      of transmission of H. pylori to humans via food and for implementation of a
      correct risk analysis for food safety purposes.

PMID- 17188209
TI  - The development of a 'clean sheep policy' in compliance with the new Hygiene
      Regulation (EC) 853/2004 (Hygiene 2).
AB  - The aim of this research was to identify the risk factors associated with the
      transfer of bacterial contamination from the fleece to the ovine carcass thereby
      providing the scientific basis for the development and validation of a clean
      sheep policy. Two hundred sheep in lairage were graded into five categories each
      consisting of 40 sheep. The categories were as follows; (A) clean and dry; (B)
      clean and wet; (C) dirty and dry; (D) dirty and wet and (E) visible dags (dung
      clotted tufts of wool) categorized by the chief veterinary inspector at the
      slaughter plant based on the visual inspection of the hygienic status of the
      fleece. Microbiological evaluations of the carcasses were conducted using swab
      sampling methods. Total viable counts (TVCs), Enterobacteriaceae and coliform
      counts were obtained from 40 animals per category at four separate sites
      (brisket, shoulder, flank and rump) immediately after pelt removal. Statistical
      analysis of TVC data obtained from the carcass indicated that the dirt level of
      the fleece had a significant effect on contamination levels when the fleece was
      dry. Enterobacteriaceae and coliform counts suggest that dirt was a contributing
      risk factor regardless of wetness or dryness of the animal. The clean sheep
      policy should therefore differentiate between clean and dirty sheep and mandate
      additional hygiene measures for the latter.

PMID- 17188210
TI  - RAPD with microsatellite as a tool for differentiation of Candida genus yeasts
      isolated in brewing.
AB  - Fifteen wild yeast strains were isolated in two factories of a lager brewing
      company in Poland. Their identification with API 32C system showed mainly the
      presence of Candida sake species (7/15). To differentiate the isolates, randomly
      amplified polymorphic DNA (RAPD) with (GTG)(5), (GAC)(5), (GACA)(4)
      microsatellite primers and M13 core sequence (5'-GAG GGT GGC GGT TCT-3') were
      chosen. The results of patterns similarity are presented as dendrograms for each
      RAPD analysis and for overall patterns. On the overall patterns, all isolates
      identified as C. sake, except Strain No. 1, were regrouped in one cluster.
      Collection strain C. sake CBS 617 was similar in 46% to the cluster with six
      isolates (Strain Nos. 3, 6, 8, 11, 13, 14). The second reference strain C. sake
      CBS 159 and the Strain No. 1 were regrouped with other Candida species
      (collection strains) showing, respectively, only 20% and 42% of similarity to
      other C. sake strains. The similarity based on the overall dendrogram between
      isolate Nos. 3, 6, 8, 11, 13, 14 and C. sake CBS 617 was 49%. Between those
      strains and other Candida, the similarity was only 37%.

PMID- 17188213
TI  - Health, preventive health care, and health care access among women with
      disabilities in the 1994-1995 National Health Interview Survey, Supplement on
      Disability.
AB  - OBJECTIVES: This study presents national estimates on the health, preventive
      health care, and health care access of adult women with disabilities. We compared
      women with 1 or 2 functional limitations (FLs) and > or =3 FLs with women with no
      FLs. Topics covered included demographic characteristics, selected reported
      health measures, selected clinical preventive services, and selected access to
      care indicators and health care coverage. METHODS: Estimates in this report were
      based on data from the 1994-1995 National Health Interview Survey, Supplement on
      Disability (NHIS-D). The sample size for women > or =18 years of age used in
      producing the estimates from the combined 1994 and 1995 NHIS-D was 77,762.
      RESULTS: An estimated 16% of women > or =18 years of age had difficulty with at
      least 1 FL. Women with FLs were less likely to rate their health as excellent or
      very good and more likely to report their health as fair or poor when compared
      with women with no FLs. Women with FLs were also more likely to report being a
      current smoker, having hypertension, being overweight, and experiencing mental
      health problems. Among women > or =65 years of age, those with FLs were also less
      likely to have received Pap smear tests within the past year and those with > or
      =3 FLs were less likely to have received mammograms within the past year than
      women with no FLs. Women with > or =3 FLs were more likely to report being unable
      to get general medical care, dental care, prescription medicines, or eyeglasses,
      regardless of age group, compared with women with no FLs. The main reasons
      reported for being unable to receive general care were financial problems or
      limitations in insurance. These findings suggest that increased attention to the
      health care needs of women with disabilities from researchers, clinicians, and
      public health professionals is warranted.

PMID- 17188212
TI  - Disability and receipt of clinical preventive services among women.
AB  - BACKGROUND: More individuals are surviving catastrophic injuries and living
      longer with persistent disability; however, their receipt of clinical preventive
      services is not well understood as compared with those without disabilities given
      the dual focus of care on both primary prevention and the prevention of secondary
      complications related to their disabilities. METHODS: Longitudinal analyses of
      1999-2002 Medical Expenditure Survey (MEPS). Study sample consisted of 3,183
      community-dwelling women aged 51-64 years and followed for 2 full years. Women
      with disabilities were defined as having reported any limitation in any area of
      activity of daily living in 2 years. Recommended clinical preventive services
      were defined as receiving the following at the recommended intervals: colorectal,
      cervical, and breast cancer; cholesterol screening; and influenza immunization.
      chi(2) tests and multiple logistic regressions were used to examine variations in
      use of clinical preventive services. RESULTS: Overall, 23% of the women in the
      study (n = 835) were disabled. Disabled women, however, were less likely to
      receive mammography and Pap smears within the recommended intervals. However,
      disabled women were more likely to receive influenza immunization, cholesterol
      screening, and colorectal screening within the recommended intervals. Among the
      disabled, usual source of care and health insurance remained significant
      predictors of receipt of clinical preventive services across all types,
      CONCLUSIONS: Disabled women were less likely to receive some of the cancer
      screening services, suggesting a need for targeted interventions to promote
      breast cancer and cervical cancer screening. Increased access to health care
      insurance and health care providers may also help.

PMID- 17188214
TI  - Health service use and outcomes among disabled Medicaid pregnant women.
AB  - PURPOSE: We investigated differences in health service use and pregnancy outcomes
      among women enrolled in Medicaid under eligibility categories for the blind and
      disabled and those enrolled under other eligibility categories. METHODS: We used
      Medicaid enrollment and claims data to create episodes of pregnancy- and delivery
      related care for women with and without disabilities who had Medicaid-covered
      deliveries in Florida, Georgia, and New Jersey during 1995 and Texas during 1997.
      We linked birth certificate information on prenatal care and birth outcomes to
      the files for Georgia and Texas. We then computed the unadjusted and adjusted
      odds ratios for the receipt of selected routine prenatal and illness-related
      services and the occurrence of selected pregnancy outcomes among women with
      disabilities relative to women without disabilities. FINDINGS: In all states,
      women with disabilities were more likely than women without disabilities to have
      had continuous Medicaid coverage from preconception through the postnatal period.
      Women with disabilities were equally or less likely to have received adequate
      prenatal care compared to women without disabilities in the two study states with
      these data. They were also more likely to have had emergency room visits,
      hospital admissions during pregnancy, cesarean deliveries, and readmissions
      within 3 months of delivery in all study states. We also found women with
      disabilities to have been more likely to deliver preterm and low birthweight
      infants. CONCLUSION: Our results suggest that opportunities exist to improve
      access to prenatal care among women with disabilities enrolled in Medicaid under
      blind and disabled eligibility categories who become pregnant.

PMID- 17188215
TI  - Physical activity and nutritional behaviors of women with physical disabilities:
      physical, psychological, social, and environmental influences.
AB  - INTRODUCTION: We examined predictors of 2 important health behaviors, namely,
      physical activity and nutritional behaviors, in a sample of community-living
      women with physical disabilities (N = 386). METHOD: We conducted a cross
      sectional survey with regression analysis. RESULTS: Our regression model
      accounted for 33.5% of the variance in physical activity. Women with joint
      problems or multiple sclerosis tended to engage in less physical activity than
      those with stroke-related disabilities. Those who had lived with their disability
      longer and those experiencing greater pain tended to report less physical
      activity. Consistent with the literature, women with greater self-efficacy for
      physical activity tended to engage in more physical activity. The regression
      model for nutritional behaviors accounted for 37.9% of the variance. Women with
      better mobility, greater self-efficacy for nutrition, and more vitality had
      better nutritional behaviors while those who needed assistance with activities of
      daily living, had lower social functioning scores, and were engaged in more
      productive activities reported poorer nutritional behaviors. CONCLUSIONS: Our
      findings highlight the importance of self-efficacy for improving health
      behaviors. Further research is needed to develop a new paradigm for the
      measurement of health behaviors, one that focuses on individual improvement
      rather than comparison to a norm, and health promoting interventions that are
      responsive to the needs and life circumstances of women with physical
      disabilities.

PMID- 17188216
TI  - Improving the health and health behaviors of women aging with physical
      disabilities: A peer-led health promotion program.
AB  - OBJECTIVE: To examine the efficacy of a health promotion program for women aging
      with physical disabilities. METHOD: A sample of 137 middle-aged and older women
      with physical disabilities was randomly assigned to either an 8-week health
      promotion program or to a wait-list control group. Both groups completed
      questionnaires before, immediately after, and 3 months after the intervention.
      RESULTS: Relative to women in the control group, women in the health-promotion
      program demonstrated improvements in health behaviors, most of which were
      maintained at follow-up. The intervention group showed some improvements on
      measures of physical health, but there was little evidence of improvement in
      psychological health outcomes. Testing our theoretical model, self-efficacy was
      supported as a mediator of the effect of the intervention on health behaviors,
      and health behaviors combined with self-efficacy were supported as mediators of
      the effect of the intervention on physical health outcomes. Contrary to our
      hypotheses, our measures of social support and social connectedness were not
      affected by the intervention. CONCLUSIONS: A brief, peer-led, group health
      promotion program resulted in improved scores on measures of self-efficacy,
      increased health behavior, and physical health. Self-efficacy, which was
      supported as a mediator in the effect of the intervention on behaviors and health
      outcomes, should remain an important focus of future interventions with this
      population.

PMID- 17188217
TI  - Associations between fracture incidence and use of depot medroxyprogesterone
      acetate and anti-epileptic drugs in women with developmental disabilities.
AB  - PURPOSE: We sought to evaluate any association between incidence of osteoporotic
      fractures and use of depot medroxyprogesterone acetate (DMPA) and/or anti
      epileptic drugs (AEDs) among women and girls with developmental disabilities.
      METHODS: Cross-sectional population-based observational study of all
      noninstitutionalized females with developmental disabilities age >/=13 who
      received fee-for-service Medicaid in Washington State during 2002 (n = 6,773),
      using administrative data. MAIN FINDINGS: In a sample of 6,773 females, 140 women
      (2%) had an osteoporotic fracture during 2002. Among 340 users of DMPA, 13 (3.8%)
      had an osteoporotic fracture with an odds ratio of 2.4 (95% confidence interval
      [CI], 1.3-4.4) for fracture compared to nonusers. Among 1,909 users of AEDs, 60
      (3.1%) had an osteoporotic fracture with an odds ratio of 1.9 (95% CI, 1.3-2.6)
      for fracture compared to nonusers. We controlled for use of drugs (DMPA or AEDs),
      age and race (as white or other racial and ethnic groups). CONCLUSIONS: Use of
      either AEDs or DMPA by women with developmental disabilities is associated with
      significantly increased incidence of fracture. Women and girls who have
      developmental disabilities may be poor candidates for DMPA use owing to increased
      risk of fractures. Further research is indicated to 1) determine the specific
      risks profile of DMPA for this population, 2) explore alternative means of
      managing significant menstrual problems and contraceptive needs in this
      population, and 3) screen current and previous users of DMPA and chronic users of
      AEDs for osteoporosis risk, regardless of age.

PMID- 17188218
TI  - Illness perceptions and related outcomes among women with fibromyalgia syndrome.
AB  - PURPOSE: Fibromyalgia syndrome (FMS) is characterized by widespread
      musculoskeletal pain, multiple tender points, and fatigue, and affects 3-6
      million Americans, 75% of whom are female. The purpose of the present study was
      to examine the illness perceptions of women with FMS using Leventhal's common
      sense self-regulation model. DESIGN: Ninety-one women with FMS took part in this
      study. Pearson correlations and stepwise multiple regressions were used to assess
      relationships among variables and explanation of variance in the outcomes of
      health behaviors, FMS impact, and subjective physical and mental health. RESULTS:
      Participants viewed their FMS as chronic with a somewhat fluctuating course,
      having serious consequences in their lives, and difficult to understand in a
      coherent fashion. The women tended to find their FMS emotionally distressing and
      unamenable to personal control or efficacious treatment. Emotional
      representations explained 41% of the variance in mental health scores and 17% in
      reported health behaviors. CONCLUSIONS: Overall, this sample of women with FMS
      had fairly negative perceptions of their illness. As suggested by Leventhal's
      model, cognitive and emotional representations predicted different outcomes.
      Interventions that address psychological as well as the physical components of
      the illness experience may offer benefits for women with FMS.

PMID- 17188220
TI  - Sexual assault patterns among women with and without disabilities seeking
      survivor services.
AB  - INTRODUCTION: The primary research questions were 1) how do sexual assault
      patterns differ for women with disabilities as compared with women without
      disabilities and 2) how do patterns differ among women with different
      disabilities? METHODS: Study data were derived from initial encounters of 16,672
      women survivors of sexual assault who sought state-funded sexual assault survivor
      services in Massachusetts from 1987 through 1995. Bivariate analyses and fixed
      effects logistic regression models compared sexual assault patterns including
      survivor responses for women with and without disabilities and among women with 5
      different single disabilities. RESULTS: More than 10% of survivors reported > or
      =1 disability. If a woman had a history of a previous assault or was > or =30 at
      time of assault, she was significantly more likely to report a disability as
      compared to the referents (no history of assault or <30). Among women with a
      single disability, a survivor who delayed seeking services > or =6 months was
      more likely to have a mental health disability. In contrast, a survivor who had a
      cognitive disability was more likely to report sooner than 6 months compared with
      a survivor with other single disabilities. CONCLUSIONS: Differences were found
      between disabled and nondisabled groups as well as among women with different
      single disabilities. Some findings, such as those suggesting differential access,
      may require disability group-specific interventions, whereas other variations can
      be addressed at the individual client level. State-funded sexual assault survivor
      service providers may use these findings to improve outreach and service
      provision strategies.

PMID- 17188219
TI  - Diabetes care among veteran women with disability.
AB  - OBJECTIVE: The primary objective of this study was to analyze predictors of
      diabetes care consistent with performance standards among women Veterans Health
      Administration (VHA) clinic users with disability enrollment status. METHODS:
      This is a retrospective cohort study using VHA and Medicare files of VHA clinic
      users with diabetes. Diabetes care measures consisted of annual testing for
      hemoglobin A(1c) (HbA(1c)), low-density lipoprotein cholesterol (LDL-C), and poor
      HbA(1c) (>9%) and LDL-C (> or =130 mg/dL) control in fiscal year 2000. Chi-square
      tests and logistic regressions were used to assess subgroup differences in
      diabetes care. Independent variables included demographic characteristics and
      physical and psychiatric comorbidities. POPULATION: Study population was based on
      veteran women <65 years of age who used VHA clinics; we identified 2,344 women as
      having coexisting disability and diabetes and 2,766 women with diabetes and
      without disability. FINDINGS: Among veteran women with diabetes and disability,
      65% received > or =1 HbA(1c) test, and 54% received a LDL-C test; 25% and 30% had
      poor HbA(1c) and LDL-C control, respectively. In logistic regressions, none of
      the independent variables had significant effects on poor HbA(1c) or LDL-C
      control, except that African Americans were more likely to have poor HbA(1c)
      control than whites. Significant age effects were noted in rates of HbA(1c) and
      LDL testing. Comparison of diabetes care measures between women with and without
      disability indicated that those with disability were more likely to receive
      HbA(1c) and LDL-C tests; no significant differences in HbA(1c) and LDL-C control
      were noted. CONCLUSIONS: Disability status of women veterans was not a barrier to
      diabetes care consistent with performance standards. Our findings suggest that to
      improve diabetes care, subgroup-specific interventions, rather than a global
      approach, are warranted.

PMID- 17188223
TI  - Internationalism, infectious diseases and international development: there is an
      elephant in the living room.

PMID- 17188221
TI  - An examination of depression through the lens of spinal cord injury. Comparative
      prevalence rates and severity in women and men.
AB  - PURPOSE: This study describes the prevalence of probable major depressive
      disorder (MDD) as well as other depressive disorders (ODD) and severity of
      depressive symptoms in a national sample of women with spinal cord injury (SCI)
      and compares them with a case-matched sample of men with SCI. METHODS: A sample
      of 585 women was drawn and case-matched with men from the SCI Model System
      National SCI Database according to level/completeness of injury, follow-up year,
      and age. The outcome measure of depression was the Patient Health Questionnaire.
      MAIN FINDINGS: Prevalence rates for women were 7.9% for probable MDD and 9.7% for
      ODD; rates for men were 9.9% and 10.3%, respectively. Logistic regression
      revealed that women who were divorced or at year 1 follow-up had a higher odds of
      having probable MDD (odds ratio [OR], 3.4 and 2.9, respectively). Employed women
      and men had significantly lower odds of probable MDD (OR, 0.274 and 0.358,
      respectively). Statistically significant differences were not found in gender
      comparisons for either probable MDD or symptom severity, which also were not
      associated with injury characteristics. CONCLUSION: The most significant, and
      unexpected, research finding is the absence of gender differences in probable MDD
      and symptom severity. Results challenge notions that depression will necessarily
      follow SCI; that injury characteristics determine the development and severity of
      depression; and that women experience a greater burden of depression than men.
      The main clinical implication is that depression screening and referral should be
      a routine feature of health care for women living with SCI, as well as for their
      male counterparts. Furthermore, nearly one fourth of women and men reported
      experiencing some or greater difficulty in daily life and relationships in the
      absence of probable depressive disorder, warranting monitoring of subsyndromal
      depression as well.

PMID- 17188222
TI  - Stress self-management: an intervention for women with physical disabilities.
AB  - PURPOSE: We sought to develop and evaluate the efficacy of an innovative, theory
      driven, group stress self-management intervention designed to ameliorate stress
      and promote health among women with physical disabilities such as spinal cord
      injury, multiple sclerosis, and arthritis. METHODS: We recruited a voluntary
      sample of 78 community-living women with disabilities who were randomly assigned
      to either the group stress management intervention or the wait-listed control
      group, and we used a within- and between-groups pretest/posttest design with a 3
      month follow-up. RESULTS: Group differences in changes over time on measures of
      perceived stress and mental health offer support for the efficacy of the
      intervention. At the 3-month follow-up assessment, the intervention group also
      showed greater improvement on measures of pain and role limitations owing to
      physical health when compared the wait-listed control group. Perceived stress was
      supported as a mediator of the effect of the intervention on mental health. We
      found support for social connectedness and self-efficacy as mediators of the
      relation between the intervention and perceived stress; however, there was
      relatively weak evidence for differential change over time in those proposed
      mediators. CONCLUSION: This study provides the first of its kind, that is, an
      evaluation of the efficacy of a stress self-management intervention designed
      specifically for women with physical disabilities. The results are consistent
      with a model in which the stress management intervention enhances self-efficacy
      and social connectedness, which leads to reduced stress, which then contributes
      to improved mental health.

PMID- 17188224
TI  - The Bead blot: a method for identifying ligand-protein and protein-protein
      interactions using combinatorial libraries of peptide ligands.
AB  - Small molecules that bind proteins can be used as ligands for protein
      purification and for investigating protein-protein and protein-drug interactions.
      Unfortunately, many methods used to identify new ligands to desired proteins
      suffer from common shortcomings, including the requirement that the target
      protein be purified and/or the requirement that the ligands be selected under
      conditions different from those under which it will be used. We have developed a
      new method called the Bead blot that can (i) select ligands to unpurified
      proteins, including trace proteins, present in complex materials (e.g.,
      unfractionated plasma); (ii) select ligands to multiple proteins under a variety
      of conditions in a single experiment; and (iii) be used with libraries of
      different types of ligands. In the Bead blot, a library of ligands, synthesized
      on chromatography resin beads, is incubated with a starting material containing a
      target protein for which a ligand is sought. The proteins in the material bind to
      their complementary ligands according to specific affinity interactions. Then the
      protein-loaded beads are immobilized in a porous matrix, and the proteins are
      directionally eluted from the beads and captured on a membrane superimposed on
      the beads. The location of the target protein on the membrane is determined, and
      because the position of the protein(s) on the membrane reflects the position of
      the bead(s) in the matrix, the bead that originally bound the protein is
      identified, with subsequent elucidation of the ligand sequence. Ligands to
      several targets can be identified in one experiment. Here we demonstrate the
      broad utility of this method by the selection of ligands that purify plasma
      protein complexes or that remove pathogens from whole blood with very high
      affinity constants. We also select ligands to a protein based on competitive
      elution.

PMID- 17188225
TI  - Time-resolved detection probe for homogeneous nucleic acid analyses in one-step
      format.
AB  - We report here an extension of homogeneous assays based on fluorescence intensity
      and lifetime measuring on DNA hybridization. A novel decay probe that allows
      simple one-step nucleic acid detection with subnanomolar sensitivity, and is
      suitable for closed-tube applications, is introduced. The decay probe uses
      fluorescence resonance energy transfer (FRET) between a europium chelate donor
      and an organic fluorophore acceptor. The substantial change in the acceptor
      emission decay time on hybridization with the target sequence allows the direct
      separation of the hybridized and unhybridized probe populations in a time
      resolved measurement. No additional sample manipulation or self-hybridization of
      the probes is required. The wavelength and decay time of a decay probe can be
      adjusted according to the selection of probe length and acceptor fluorophore,
      thereby making the probes applicable to multiplexed assays. Here we demonstrate
      the decay probe principle and decay probe-based, one-step, dual DNA assay using
      celiac disease-related target oligonucleotides (single-nucleotide polymorphisms
      [SNPs]) as model analytes. Decay probes showed specific response for their
      complementary DNA target and allowed good signal deconvolution based on
      simultaneous optical and temporal filtering. This technique potentially could be
      used to further increase the number of simultaneously detected DNA targets in a
      simple one-step homogeneous assay.

PMID- 17188227
TI  - Multicommutated flow-through optosensors implemented with photochemically induced
      fluorescence: determination of flufenamic acid.
AB  - This article describes a multicommutated flow injection-solid phase spectroscopy
      system implemented with photochemically induced fluorescence for the
      determination of flufenamic acid (FFA). A strongly fluorescent photoproduct is
      generated when FFA is irradiated online under UV light in a strong sulfuric
      medium. The photoproduct generated is retained on C(18) silica gel (which fills
      the detection area of the flow cell) and directly monitored on the active solid
      support at 258/442 nm (lambda(ex)/lambda(em)). After maximum signal recording,
      the sensing zone is regenerated by eluting the retained photoproduct with an
      appropriate H(2)SO(4)/MeOH solution. The sensor, completely automated, is based
      on the use of three-way solenoid valves conveniently operated by a homemade
      multicommutation software written in Java language. The system is calibrated at
      10 and 60s for sampling time, showing detection limits of 1.28 x 10(-9) and 5.33
      x 10(-10) molL(-1) and sampling rates of 38 and 28 h(-1), respectively, with
      relative standard deviations of 0.9 and 1.2%. The applicability of the method is
      demonstrated for the determination of FFA in human serum, human urine, and a
      pharmaceutical preparation without any pre-treatment. Good recovery levels were
      achieved between 90.5 and 103.7%.

PMID- 17188226
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      assay for organophosphorus toxicants bound to human albumin at Tyr411.
AB  - Our goal was to determine whether chlorpyrifos oxon, dichlorvos,
      diisopropylfluorophosphate (DFP), and sarin covalently bind to human albumin.
      Human albumin or plasma was treated with organophosphorus (OP) agent at alkaline
      pH, digested with pepsin at pH 2.3, and analyzed by matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Two singly
      charged peaks m/z 1718 and 1831, corresponding to the unlabeled peptide fragments
      containing the active site Tyr411 residue, were detected in all samples. The
      sequences of the two peptides were VRYTKKVPQVSTPTL and LVRYTKKVPQVSTPTL. The
      peptide-OP adducts of these peptides were also found. They had masses of 1854 and
      1967 for chlorpyrifos oxon, 1825 and 1938 for dichlorvos, 1881 and 1994 for DFP,
      and 1838 and 1938 for sarin; these masses fit a mechanism whereby OP bound
      covalently to Tyr411. The binding of DFP to Tyr411 of human albumin was confirmed
      by electrospray tandem mass spectrometry and analysis of product ions. None of
      the OP-albumin adducts lost an alkoxy group, leading to the conclusion that aging
      did not occur. Our results show that OP pesticides and nerve agents bind
      covalently to human albumin at Tyr411. The presence of Tyr411 on an exposed
      surface of albumin suggests that an antibody response could be generated against
      OP-albumin adducts.

PMID- 17188228
TI  - Purification method directly influences effectiveness of an epidermal growth
      factor-coupled targeting agent for noninvasive tumor detection in mice.
AB  - Receptor targeting is an effective method of enhancing fluorescence signal in
      tumors for optical imaging. We previously used epidermal growth factor (EGF)
      conjugated to IRDye 800CW to detect and track orthotopic prostate tumors in mice.
      In this study, our goal was to identify a reliable assay for targeting agent
      integrity in vitro that correlated with signal strength in vivo. Binding of IRDye
      800CW EGF to intact A431 human epidermoid carcinoma cells was quantified in a
      microplate assay. Specificity was confirmed by competition with unlabeled EGF or
      monoclonal antibody blocking. Biological activity of intact and damaged targeting
      agents relative to unlabeled EGF was determined by binding and stimulation of
      extracellular signal-regulated kinase (ERK) phosphorylation. Both assays
      indicated a reduction of up to 60% of the fluorescence intensity with damaged
      agents. Using a research prototype imaging system optimized for IRDye 800CW
      detection, we compared the efficacy of intact and damaged targeting agents for
      imaging subcutaneous tumors in mice. In live animal images and in sections of the
      excised tumors, damaged targeting agents consistently yielded diminished
      fluorescence signals corresponding to the reduction observed in microplate
      assays. This is the first study to directly correlate targeting agent signal
      strength in whole cell binding, In-Cell Western, and in vivo near-infrared
      imaging.

PMID- 17188230
TI  - Studies of carotenoid one-electron reduction radicals.
AB  - The relative reduction potentials of a variety of carotenoids have been
      established by monitoring the reaction of carotenoid radical anion (CAR1(*-))
      with another carotenoid (CAR2) in hexane and benzene. This order is consistent
      with the reactivities of the carotenoid radical anions with porphyrins and oxygen
      in hexane. In addition, investigation of the reactions of carotenoids with
      reducing radicals in aqueous 2% Triton-X 100, such as carbon dioxide radical
      anion (CO2(*-)), acetone ketyl radical (AC(*-)) and the corresponding neutral
      radical (ACH(*)), reveals that the reduction potentials for beta-carotene and
      zeaxanthin lie in the range -1950 to -2100 mV and those for astaxanthin,
      canthaxanthin and beta-apo-8'-carotenal are more positive than -1450 mV. This
      illustrates that the presence of a carbonyl group causes the reducing ability to
      decrease. The radical cations have been previously shown to be strong oxidising
      agents and we now show that the radical anions are very strong reducing agents.

PMID- 17188229
TI  - Evaluation of quantification methods for real-time PCR minor groove binding
      hybridization probe assays.
AB  - Real-time PCR data analysis for quantification has been the subject of many
      studies aimed at the identification of new and improved quantification methods.
      Several analysis methods have been proposed as superior alternatives to the
      common variations of the threshold crossing method. Notably, sigmoidal and
      exponential curve fit methods have been proposed. However, these studies have
      primarily analyzed real-time PCR with intercalating dyes such as SYBR Green.
      Clinical real-time PCR assays, in contrast, often employ fluorescent probes whose
      real-time amplification fluorescence curves differ from those of intercalating
      dyes. In the current study, we compared four analysis methods related to recent
      literature: two versions of the threshold crossing method, a second derivative
      maximum method, and a sigmoidal curve fit method. These methods were applied to a
      clinically relevant real-time human herpes virus type 6 (HHV6) PCR assay that
      used a minor groove binding (MGB) Eclipse hybridization probe as well as an
      Epstein-Barr virus (EBV) PCR assay that used an MGB Pleiades hybridization probe.
      We found that the crossing threshold method yielded more precise results when
      analyzing the HHV6 assay, which was characterized by lower signal/noise and less
      developed amplification curve plateaus. In contrast, the EBV assay, characterized
      by greater signal/noise and amplification curves with plateau regions similar to
      those observed with intercalating dyes, gave results with statistically similar
      precision by all four analysis methods.

PMID- 17188231
TI  - Demonstration of phycobilisome mobility by the time- and space-correlated
      fluorescence imaging of a cyanobacterial cell.
AB  - The cell-wide mobility of PBSs was confirmed by synchronously monitoring the
      fluorescence recovery after photobleaching (FRAP) and the fluorescence loss in
      photobleaching (FLIP). On the other hand, a fluorescence recovery was still
      observed even if PBSs were immobile (PBSs fixed on the membranes by betaine and
      isolated PBSs fixed on the agar plate) or PBS mobility was unobservable (cell
      wholly bleached). Furthermore, it was proved that some artificial factors were
      involved not only in FRAP but also in FLIP, including renaturation of the
      reversibly denatured proteins, laser scanning-induced fluorescence loss and photo
      damage to the cell. With consideration of the fast renaturation component in
      fluorescence recovery, the diffusion coefficient was estimated to be tenfold
      smaller than that without the component. Moreover, it was observed that the
      fluorescence intensity on the bleached area was always lower than that on the non
      bleached area, even after 20 min, while it should be equal if PBSs were mobile
      freely. Based on the increasing proportion of the PBSs anti-washed to Triton X
      100 (1%) with prolonged laser irradiation to the cells locked in light state 1 by
      PBQ, it was concluded that some PBSs became immobile due to photo-linking to
      PSII.

PMID- 17188234
TI  - Fusarium Tri4 encodes a key multifunctional cytochrome P450 monooxygenase for
      four consecutive oxygenation steps in trichothecene biosynthesis.
AB  - Fusarium Tri4 encodes a cytochrome P450 monooxygenase (CYP) for hydroxylation at
      C-2 of the first committed intermediate trichodiene (TDN) in the biosynthesis of
      trichothecenes. To examine whether this CYP further participates in subsequent
      oxygenation steps leading to isotrichotriol (4), we engineered Saccharomyces
      cerevisiae for de novo production of the early intermediates by introducing cDNAs
      of Fusarium graminearum Tri5 (FgTri5 encoding TDN synthase) and Tri4 (FgTri4).
      From a culture of the engineered yeast grown on induction medium (final pH 2.7),
      we identified two intermediates, 2alpha-hydroxytrichodiene (1) and 12,13-epoxy
      9,10-trichoene-2alpha-ol (2), and a small amount of non-Fusarium trichothecene
      12,13-epoxytrichothec-9-ene (EPT). Other intermediates isotrichodiol (3) and 4
      were identified in the transgenic yeasts grown on phosphate-buffered induction
      medium (final pH 5.5-6.0). When Trichothecium roseum Tri4 (TrTri4) was used in
      place of FgTri4, 4 was not detected in the culture. The three intermediates, 1,
      2, and 3, were converted to 4,15-diacetylnivalenol (4,15-diANIV) when fed to a
      toxin-deficient mutant of F. graminearum with the FgTri4+ genetic background
      (viz., by introducing a FgTri5- mutation), but were not metabolized by an FgTri4-
      mutant. These results provide unambiguous evidence that FgTri4 encodes a
      multifunctional CYP for epoxidation at C-12,13, hydroxylation at C-11, and
      hydroxylation at C-3 in addition to hydroxylation at C-2.

PMID- 17188233
TI  - Polar positional information in Escherichia coli spherical cells.
AB  - Shigella surface protein IcsA and its cytoplasmic derivatives are localized to
      the old pole of rod-shaped cells when expressed in Escherichia coli. In spherical
      mreB cells, IcsA is targeted to ectopic sites and close to one extremity of actin
      like MamK filament. To gain insight into the properties of the sites containing
      polar material, we studied the IcsA localization in spherical cells. GFP was
      exported into the periplasm via the Tat pathway and used as a periplasmic space
      marker. GFP displayed zonal fluorescence in both mreB and rodA-pbpA spherical E.
      coli cells, indicating an uneven periplasmic space. Deconvolution images revealed
      that the cytoplasmic IcsA fused to mCherry was localized outside or at the edge
      of the GFP zones. These observations strongly suggest that polar material is
      restricted to the positions where the periplasm possesses particular structural
      or biochemical properties.

PMID- 17188232
TI  - G protein coupled receptor structure and activation.
AB  - G protein coupled receptors (GPCRs) are remarkably versatile signaling molecules.
      The members of this large family of membrane proteins are activated by a spectrum
      of structurally diverse ligands, and have been shown to modulate the activity of
      different signaling pathways in a ligand specific manner. In this manuscript I
      will review what is known about the structure and mechanism of activation of
      GPCRs focusing primarily on two model systems, rhodopsin and the beta(2)
      adrenoceptor.

PMID- 17188235
TI  - A comparison study in the proteomic signatures of multipotent germline stem
      cells, embryonic stem cells, and germline stem cells.
AB  - Germline stem (GS) cells can only differentiate into germline cells, while
      multipotent germ stem (mGS) cells, like embryonic stem (ES) cells, can
      differentiate into various somatic cells and tissues. The proteomic profiles in
      GS and mGS cells were compared by two-dimensional gel electrophoresis. Ten down
      regulated and 16 up-regulated proteins were differentially expressed in mGS cells
      in comparison to GS cells, and these proteomic characteristics were very much
      similar to those in ES cells indicating that multipotency of mGS and ES cells is
      based on a common molecular event(s). Protein identification by mass spectrometry
      revealed that these proteins were functionally involved in cell signaling,
      transcription factors, metabolism, and protein folding. The identified proteins
      in the present study may thus reveal its biological characteristics and
      functional property in self-renewal and multipotency.

PMID- 17188236
TI  - High resolution crystal structures of the p120 RasGAP SH3 domain.
AB  - X-ray structures of two crystal forms of the Src homology 3 domain (SH3) of the
      Ras GTPase activating protein (RasGAP) were determined at 1.5 and 1.8A
      resolution. The overall structure comprises a single domain with two tightly
      packed beta-sheets linked by a short helical segment. An important motif for
      peptide binding in other SH3 domains is not conserved in RasGAP. The RasGAP SH3
      domain forms dimers in the crystal structures, which may provide new functional
      insight. The dimer interface involves residues also present in a peptide
      previously identified as an apoptotic sensitizer of tumor cells.

PMID- 17188237
TI  - In vivo distribution and localization of chorein.
AB  - Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disorder caused by
      loss of function mutations in the VPS13A gene encoding chorein. In this study, we
      produced an antibody against chorein and examined its protein-level expression
      and localization in mouse. Immunoblot analysis revealed that chorein was
      expressed in a gene dose-dependent manner in the VPS13A deletion-mice that we
      recently developed, which confirms the sensitivity of the antibody. Chorein was
      highly expressed in testis, kidney, spleen, and brain, and was expressed
      ubiquitously in various brain regions. Subcellular analysis of the brain showed
      high levels of chorein in microsomal and synaptosomal fractions.
      Immunohistochemically, chorein-like immunoreactivity was ubiquitously observed in
      the brain in the neuronal perinuclear region, cytoplasm and fibers. In testis and
      kidney, clear cell-specific patterns of chorein-like immunoreactivity were
      detected. Our findings provide basic information on chorein in vivo and may
      contribute to taking the first step toward understanding molecular pathogenesis
      of ChAc.

PMID- 17188239
TI  - Variation in ACE activity affects myogenic differentiation in C2C12 cells.
AB  - Variation in ACE activity is related to affect the skeletal muscle function. To
      elucidate the mechanism by which ACE affects skeletal muscle function, we
      examined the effects of loss and gain of ACE activity on myogenic differentiation
      in C2C12 myoblasts. The treatment of captopril, an ACE inhibitor, in
      differentiating cells significantly induced the up-regulation of myosin heavy
      chain, and the hypertrophic myotubes. In addition, an AT2 antagonist PD123319,
      not AT1 antagonist losartan, induced the up-regulation of myosin heavy chain. On
      the other hand, overexpression of ACE induced the down-regulation of myosin heavy
      chain. These results suggest that ACE negatively regulate the myogenesis through
      the mechanism at least in part via production of angiotensin II followed by its
      binding to AT2 receptor.

PMID- 17188238
TI  - Regulation of N-cadherin-based cell-cell interaction by JSAP1 scaffold in PC12h
      cells.
AB  - We previously reported that the level of c-Jun NH2-terminal kinase (JNK)/stress
      activated protein kinase-associated protein 1 (JSAP1), a scaffold protein for JNK
      signaling, increases dramatically during nerve growth factor (NGF)-induced
      differentiation of PC12h cells. In the present study, we investigated the
      function of JSAP1 during PC12h cell differentiation by knocking down the level of
      JSAP1. The depletion of JSAP1 caused NGF-treated PC12h cells to form aggregates
      and impaired their differentiation. The aggregation was not observed in JSAP1
      depleted cells that were untreated or treated with epidermal growth factor.
      Immunocytochemical studies indicated that N-cadherin, but not E-cadherin, was
      localized to sites of cell-cell contact in the aggregated cells. Furthermore, an
      inhibitory anti-N-cadherin antibody completely blocked the aggregation. Taken
      together, these results suggest that JSAP1 regulates cell-cell interactions in
      PC12h cells specifically in the NGF-induced signaling pathway, and does so by
      modulating N-cadherin.

PMID- 17188240
TI  - Activation of Bak in ultrasound-induced, JNK- and p38-independent apoptosis and
      its inhibition by Bcl-2.
AB  - The molecular mechanisms underlying ultrasound-induced apoptosis remain poorly
      understood. We have demonstrated that in Jurkat cells, the over-expression of the
      anti-apoptotic protein Bcl-2 inhibited ultrasound-induced apoptosis, but not
      necrosis. Inhibition of caspase activity also protected the cells from apoptosis,
      but not from necrosis, showing the involvement of different mechanisms in
      ultrasound-induced apoptosis and necrosis. Bak, a pro-apoptotic member of the Bcl
      2 family proteins, was activated by ultrasound and its activation was completely
      inhibited by Bcl-2 over-expression, but not by caspase inhibition. Antioxidant N
      acetyl cysteine did not protect the cells from ultrasound-induced apoptosis or
      necrosis, nor did the inhibition of either c-Jun N-terminal kinase or p38, key
      factors in the radical oxygen species (ROS)-mediated cell stress response,
      suggesting that ROS do not play a crucial role in ultrasound-induced apoptosis.
      Our results confirm that ultrasound induces apoptosis via a pathway that involves
      Bak, Bcl-2, and caspases, but not ROS.

PMID- 17188241
TI  - Catalytic loop motion in human glutathione synthetase: A molecular modeling
      approach.
AB  - Conformational changes of three flexible loops (G, A, and S) in human glutathione
      synthetase (hGS) arise to accommodate the substrates inside the active site. The
      crystal structure of hGS, a member of the ATP-grasp superfamily, has been
      reported only for the product-enzyme complex. To study the function of the hGS
      loops, molecular dynamics simulations are performed on three different
      conformational models: unbound enzyme, reactant-enzyme, and product-enzyme
      complex of hGS. The conformational changes among the three models are analyzed
      and the roles of the loops during the catalytic process are described. The
      modeled structures of hGS show that the central portions of the G- and A-loop
      have a double role in the reactant complex conformation: they bind the substrates
      and simultaneously interact with each other through an extensive network of
      hydrogen bonds. The present study proposes that these favorable loop-ligand and
      loop-loop interactions are required for opening and closing of the active site of
      hGS. Additionally, this research identifies important amino acid residues and
      explains their function within the catalytic loops of hGS.

PMID- 17188242
TI  - Siah-1 facilitates ubiquitination and degradation of factor inhibiting HIF-1alpha
      (FIH).
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) has a central role in
      neuroprotective responses to hypoxia in the brain. Hydroxylation of HIF-1alpha by
      prolyl-hydroxylase PHD and aspargynyl-hydroxylase FIH (factor inhibiting HIF
      1alpha) causes proteasomal degradation and transcriptional inhibition of HIF
      1alpha. Siah ubiquitin ligases regulate the abundance of PHD via targeting for
      proteasomal degradation. The present study identified Siah-1 as a binding partner
      for another hydroxylase FIH. Siah-1 and FIH coimmunoprecipitated each other in
      mammalian cells. Siah-1 was found both to interact with the JmjC domain of FIH
      through its substrate-binding domain and to specifically ubiquitinate FIH via its
      RING finger domain. Siah-1 facilitated FIH degradation via the ubiquitin
      proteasome pathway under hypoxic conditions. Such findings suggest that Siah
      ubiquitin ligases might play a role as up-stream regulators of both hydroxylases
      for HIF-1alpha, i.e., PHD and FIH, by targeting them for proteasomal degradation,
      leading to increased HIF-1alpha abundance, and transcriptional activity in
      hypoxia.

PMID- 17188243
TI  - IP3-independent signalling of OX1 orexin/hypocretin receptors to Ca2+ influx and
      ERK.
AB  - OX1 orexin receptors (OX1R) have been shown to activate receptor-operated Ca2+
      influx pathways as their primary signalling pathway; however, investigations are
      hampered by the fact that orexin receptors also couple to phospholipase C, and
      therewith inositol-1,4,5-trisphosphate (IP3)-dependent Ca2+ release. We have here
      devised a method to block the latter signalling in order to focus on the
      mechanism of Ca2+ influx activation by OX1R in recombinant systems. Transient
      expression of the IP3-metabolising enzymes IP3-3-kinase-A (inositol-1,4,5
      trisphosphate-->inositol-1,3,4,5-tetrakisphosphate) and type I IP3-5-phosphatase
      (inositol-1,4,5-trisphosphate-->inositol-1,4-bisphosphate) almost completely
      attenuated the OX1R-stimulated IP3 elevation and Ca2+ release from intracellular
      stores. Upon attenuation of the IP3-dependent signalling, the receptor-operated
      Ca2+ influx pathway became the only source for Ca2+ elevation, enabling
      mechanistic studies on the receptor-channel coupling. Attenuation of the IP3
      elevation did not affect the OX1R-mediated ERK (extracellular signal-regulated
      kinase) activation in CHO cells, which supports our previous finding of the major
      importance of receptor-operated Ca2+ influx for this response.

PMID- 17188244
TI  - Checkpoint deficient rad53-11 yeast cannot accumulate dNTPs in response to DNA
      damage.
AB  - Deoxyribonucleotide pools are maintained at levels that support efficient and yet
      accurate DNA replication and repair. Rad53 is part of a protein kinase regulatory
      cascade that, conceptually, promotes dNTP accumulation in four ways: (1) it
      activates the transcription of ribonucleotide reductase subunits by inhibiting
      the Crt1 repressor; (2) it plays a role in relocalization of ribonucleotide
      reductase subunits RNR2 and RNR4 from nucleus to cytoplasm; (3) it antagonizes
      the action of Sml1, a protein that binds and inhibits ribonucleotide reductase;
      and (4) it blocks cell-cycle progression in response to DNA damage, thus
      preventing dNTP consumption through replication forks. Although several lines of
      evidence support the above modes of Rad53 action, an effect of a rad53 mutation
      on dNTP levels has not been directly demonstrated. In fact, in a previous study,
      a rad53-11 mutation did not result in lower dNTP levels in asynchronous cells or
      in synchronized cells that entered the S-phase in the presence of the RNR
      inhibitor hydroxyurea. These anomalies prompted us to investigate whether the
      rad53-11 mutation affected dNTP levels in cells exposed to a DNA-damaging dose of
      ethylmethyl sulfonate (EMS). Although dNTP levels increased by 2- to 3-fold in
      EMS treated wild-type cells, rad53-11 cells showed no such change. Thus, the
      results indicate that Rad53 checkpoint function is not required for dNTP pool
      maintenance in normally growing cells, but is required for dNTP pool expansion in
      cells exposed to DNA-damaging agents.

PMID- 17188245
TI  - Differentiation of an ameloblast-lineage cell line (ALC) is induced by Sonic
      hedgehog signaling.
AB  - Sonic hedgehog (Shh), one of the essential molecules for embryogenesis and
      organogenesis, is strongly expressed in the enamel knot, which represents the
      signaling center for odontogenesis due to the presence of essential secretory
      molecules. Here, we investigated the effects of Shh on ameloblast differentiation
      using a mouse ameloblast-lineage cell line (ALC). In the presence of Shh, the
      expression of amelogenin and ameloblastin was up-regulated, and their promoter
      activities were also elevated. Subcutaneous implantation of Shh-treated ALC into
      the dorsa of C57/Bl6J mouse caused increased expression of amelogenin and
      ameloblastin. Forced expression of Gli1, a major transcription factor in Shh
      signaling, up-regulated both amelogenin and ameloblastin, while Gli1-specific
      RNAi blocked their expression. These results suggest that Shh directly promotes
      ALC differentiation, and that Gli1 may be responsible for the signal mediation of
      Shh.

PMID- 17188246
TI  - Reduced cerebral ischemia-reperfusion injury in Toll-like receptor 4 deficient
      mice.
AB  - Inflammatory reaction plays an important role in cerebral ischemia-reperfusion
      injury, however, its mechanism is still unclear. Our study aims to explore the
      function of Toll-like receptor 4 (TLR4) in the process of cerebral ischemia
      reperfusion. We made middle cerebral artery ischemia-reperfusion model in mice
      with line embolism method. Compared with C3H/OuJ mice, scores of cerebral water
      content, cerebral infarct size and neurologic impairment in C3H/Hej mice were
      obviously lower after 6 h ischemia and 24 h reperfusion. Light microscopic and
      electron microscopic results showed that cerebral ischemia-reperfusion injury in
      C3H/Hej mice was less serious than that in C3H/OuJ mice. TNF-alpha and IL-6
      contents in C3H/HeJ mice were obviously lower than that in C3H/OuJ mice with
      ELISA. The results showed that TLR4 participates in the process of cerebral
      ischemia-reperfusion injury probably through decrease of inflammatory cytokines.
      TLR4 may become a new target for prevention of cerebral ischemia-reperfusion
      injury. Our study suggests that TLR4 is one of the mechanisms of cerebral
      ischemia-reperfusion injury besides its important role in innate immunity.

PMID- 17188247
TI  - Genistein induces apoptosis in human hepatocellular carcinomas via interaction of
      endoplasmic reticulum stress and mitochondrial insult.
AB  - Hepatocellular carcinoma is a very common malignancy and is chemoresistant to
      currently available chemotherapeutic agents. Endoplasmic reticulum (ER) stress
      induced apoptotic pathway is suggested to be less affected by the resistance
      mechanisms, becoming a potential target of chemotherapeutic strategy. The
      anticancer effects and expression of GADD153, a transcription factor induced by
      ER stress, were examined in hepatocellular carcinoma Hep3B cells. The correlation
      between these two parameters was constructed under flavonoid stimulation with a
      correlation coefficient (r) of 0.8. The data also showed that genistein
      (isoflavone) was the most effective one. Genistein induced the activation of
      several ER stress-relevant regulators, including m-calpain, GADD153, GRP78 and
      caspase-12. Furthermore, genistein-induced effect was inhibited in cells
      transfected with antisense GADD153 cDNA, indicating a functional role of GADD153.
      Notably, genistein induced the activation of caspase-2, whereas did not cause the
      DNA damage. It also triggered the production of ROS. The antioxidant trolox
      significantly reduced ROS accumulation, but did not modify genistein-induced
      apoptotic cell death. The long-term exposure (48 h) of cells to genistein caused
      Mcl-1 down-regulation and Bad cleavage; furthermore, cyclosporin A (an inhibitor
      of mitochondrial permeability transition pore) almost completely abolished
      genistein-induced loss of mitochondrial membrane potential, and induced a 30%
      reverse of apoptosis caused by long-term treatment (48 h) of genistein,
      suggesting the involvement of mitochondrial stress in the late phase of genistein
      induced effect. Taken together, it is suggested that genistein induces the
      anticancer effect through a mechanism initiated by ER stress and facilitated by
      mitochondrial insult in Hep3B cells.

PMID- 17188248
TI  - Mitochondria are primary targets in apoptosis induced by the mixed phosphine gold
      species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) in
      melanoma cell lines.
AB  - Based on previous evidence indicating a selective cytotoxic activity of the mixed
      phosphine gold complex chlorotriphenylphosphine-1,3
      bis(diphenylphosphino)propanegold(I) for melanoma cells, we investigated the
      cellular bases of its antiproliferative effect in a panel of human melanoma cell
      lines (JR8, SK-Mel-5, Mel-501, 2/60, 2/21 and GRIG). The drug consistently
      induced a dose-dependent inhibition of cell growth, with IC50 values ranging from
      0.8 to 2.3 microM and, when tested under the same experimental conditions, its
      cytotoxic activity was higher than (from 2- to 5-fold) or comparable to that of
      cisplatin as a function of cell lines. The ability of the gold complex to
      activate programmed cell death was assessed in JR8 and 2/60 cells, and a dose
      dependent increase in cells with an apoptotic nuclear morphology was observed in
      both cell lines (up to 40 and 66% of the overall cell population, for JR8 and
      2/60 cell lines, respectively). Such an apoptotic response was mediated by a dose
      dependent loss of mitochondrial membrane potential, cytochrome c and Smac/DIABLO
      release from mitochondria into cytosol and enhanced caspase-9 and caspase-3
      catalytic activity. A reduced or completely abrogated expression of the anti
      apoptotic proteins c-IAP1, XIAP and survivin in drug-treated cells was also
      observed. Overall, results from the study indicate that chlorotriphenylphosphine
      1,3-bis(diphenylphosphino)propanegold(I) markedly inhibits melanoma cell growth
      by inducing mitochondria-mediated apoptosis and suggest it as a good candidate
      for additional evaluation as an anticancer agent against melanoma.

PMID- 17188249
TI  - Nicotinamide inhibits B lymphocyte activation by disrupting MAPK signal
      transduction.
AB  - Nicotinamide (NAm) represents both a pharmacological agent known to express cell
      preserving and anti-inflammatory properties, and a useful investigational tool to
      elucidate cellular pathways regulating a wide range of cellular functions. We
      demonstrate in this study that exogenous NAm, when used at pharmacological doses,
      inhibits activation of primary murine B lymphocytes in response to multiple
      ligands. NAm appears to affect a membrane proximal event leading to MAPKs
      activation, a transduction pathway shared by multiple receptors including the
      antigen-specific B cell receptor, CD38, CD40 and TLR4 receptors. NAm inhibited
      phospho-ERK accumulation, and only marginally affected phospho-p38 and phospho
      JNK induction upon BCR stimulation of naive B lymphocytes. Accordingly, NAm also
      affected the expression of known targets of the MAPK ERK pathway such as CD69 and
      cyclin D2. Based on a comparison with well-characterized pharmacological
      inhibitors, we suggest in this work that NAm may inhibit a post-translational
      modification mediated by a yet unidentified mono(ADP-ribose)transferase.
      Collectively, our observations indicate that in addition to its previously
      described effect on cells of the innate immune system, NAm is able to modulate
      the activity of B lymphocytes suggesting a potential role of this vitamin in
      regulating antibody-mediated autoimmune disorders.

PMID- 17188250
TI  - Excess ribonucleotide reductase R2 subunits coordinate the S phase checkpoint to
      facilitate DNA damage repair and recovery from replication stress.
AB  - Ribonucleotide reductase (RNR), which consists of R1 and R2 subunits, catalyzes a
      key step of deoxyribonucleoside triphosphate (dNTP) synthesis for DNA replication
      and repair. The R2 subunit is controlled in a cell cycle-specific manner for
      timely DNA synthesis and is negatively regulated by p53 in response to DNA
      damage. Herein we demonstrate that the presence of excess R2 subunits in p53(-/-)
      HCT-116 human colon cancer cells protects against DNA damage and replication
      stress. siRNA-mediated stable knockdown (>80%) of excess R2 subunits has no
      effect on proliferative growth but results in enhanced accumulation of gamma-H2Ax
      and delayed recovery from DNA lesions inflicted by exposure to cisplatin and
      Triapine. This accentuated induction of gamma-H2Ax in R2-knockdown cells is
      attributed to reduced ability to repair damaged DNA and overcome replication
      blockage. The lack of excess R2 subunits consequently augments chk1 activation
      and cdc25A degradation, causing impeded cell progression through the S phase and
      enhanced apoptosis in response to DNA damage and replication stress. In contrast,
      the level of R1 subunits appears to be limiting, since depletion of the R1
      subunit directly activates the S phase checkpoint due to replication stress
      associated with impaired RNR activity. These findings suggest that excess R2
      subunits facilitate DNA damage repair and recovery from replication stress
      through coordination with the S phase checkpoint in the absence of functional
      p53. Thus, the level of the R2 subunit constitutes an important determinant of
      the chemosensitivity of cancer cells and serves as a potential target for
      enhancement of DNA-damage based therapy.

PMID- 17188252
TI  - Persistent cognitive impairment in depression: the role of psychopathology and
      altered hypothalamic-pituitary-adrenocortical (HPA) system regulation.
AB  - BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA)
      system and cognitive impairment are consistent findings in depression. This study
      examines the associations between HPA system regulation, cognitive functioning,
      and psychopathology in depressed inpatients on admission and at discharge.
      METHODS: The HPA system dysregulation was evaluated with the dexamethasone
      (DEX)/corticotropin-releasing hormone (CRH) test. Cognitive assessment included
      speed of information processing, divided and selective attention, as well as
      short-term and working memory. Psychopathology was evaluated with the Hamilton
      Rating Scale for Depression (HAMD). Data from 75 depressed inpatients are
      reported, 51 (68%) of them achieved remission. RESULTS: Despite a significant
      reduction of depressive symptoms between admission and discharge, a high rate of
      patients remained cognitively impaired. Selective attention improved
      significantly in remitters and nonremitters, while speed of information
      processing increased only in remitters. The cortisol response to the DEX/CRH test
      decreased significantly only in remitters, which was uncorrelated with cognitive
      performance. In nonremitters, severity of depression was significantly correlated
      with information processing time while improvement in short-term memory was
      negatively associated with the cortisol response at discharge. CONCLUSIONS: Our
      data support the assumption that psychopathological symptoms and the HPA system
      dysregulation can be dissociated in their impact on cognitive functioning in
      depressed patients.

PMID- 17188251
TI  - Time-varying amygdala response to emotional faces in generalized social phobia.
AB  - BACKGROUND: Individuals with social phobia (SP) have altered behavioral and
      neural responses to emotional faces and are hypothesized to have deficits in
      inhibiting emotion-related amygdala responses. We tested for such amygdala
      deficits to emotional faces in a sample of individuals with SP. METHOD: We used
      functional magnetic resonance imaging (fMRI) to examine the neural substrates of
      emotional face processing in 14 generalized SP (gSP) and 14 healthy comparison
      (HC) participants. Analyses focused on the temporal dynamics of the amygdala,
      prefrontal cortex (PFC), and fusiform face area (FFA) across blocks of neutral,
      fear, contempt, anger, and happy faces in gSP versus HC participants. RESULTS:
      Amygdala responses in participants with gSP occurred later than the HC
      participants to fear, angry, and happy faces. Parallel PFC responses were found
      for happy and fear faces. There were no group differences in temporal response
      patterns in the FFA. CONCLUSIONS: This finding might reflect a neural correlate
      of atypical orienting responses among individuals with gSP. Commonly reported SP
      deficits in habituation might reflect neural regions associated with emotional
      self-evaluations rather than the amygdala. This study highlights the importance
      of considering time-varying modulation when examining emotion-related processing
      in individuals with gSP.

PMID- 17188253
TI  - Disturbances in morning cortisol secretion in association with maternal postnatal
      depression predict subsequent depressive symptomatology in adolescents.
AB  - BACKGROUND: We have previously reported higher and more variable salivary morning
      cortisol in 13-year-old adolescents whose mothers were depressed in the postnatal
      period, compared with control group adolescents whose mothers did not develop
      postnatal depression (PND). This observation suggested a biological mechanism by
      which intrafamilial risk for depressive disorder may be transmitted. In the
      current article, we examined whether the cortisol disturbances observed at 13
      years could predict depressive symptomatology in adolescents at 16 years of age.
      METHODS: We measured self-reported depressive symptoms in 16-year-old adolescents
      who had (n = 48) or had not (n = 39) been exposed to postnatal maternal
      depression and examined their prediction by morning and evening cortisol indices
      obtained via 10 days of salivary collections at 13 years. RESULTS: Elevated
      morning cortisol secretion at 13 years, and particularly the maximum level
      recorded over 10 days of collection, predicted elevated depressive symptoms at 16
      years over and above 13-year depressive symptom levels and other possible
      confounding factors. Morning cortisol secretion mediated an association between
      maternal PND and symptomatology in 16-year-old offspring. CONCLUSIONS:
      Alterations in steroid secretion observed in association with maternal PND may
      provide a mechanism by which risk for depression is transmitted from mother to
      offspring.

PMID- 17188254
TI  - The relations among putative biorisk markers in schizotypal adolescents: minor
      physical anomalies, movement abnormalities, and salivary cortisol.
AB  - BACKGROUND: Evidence suggests that prenatal insult may play a role in the
      etiology of psychotic disorders. Minor physical anomalies (MPA) are an indicator
      of abnormal fetal development and are elevated in individuals at genetic and
      behavioral risk for psychosis. Yet, there has been little empirical research on
      the relationships between MPAs and other neurobiological risk indicators. We
      hypothesized that the frequency of MPAs (an external marker of prenatal central
      nervous system [CNS] disruption) would be associated with two other biomarkers
      suggestive of disruptions in fetal neurodevelopment: movement abnormalities (an
      indicator of striatal abnormalities) and heightened cortisol secretion (an
      indicator of hypothalamic-pituitary-adrenal [HPA]/hippocampal function). METHODS:
      Participants with schizotypal personality disorder (SPD; n = 39) and both normal
      (n = 47) and other personality disorders (n = 28) control subjects were
      administered structured diagnostic interviews and assessed for MPAs, movement
      abnormalities, and salivary cortisol. RESULTS: Schizotypal personality disorder
      participants showed significantly greater MPAs and movement abnormalities and
      higher cortisol than both the normal and other personality disorders groups.
      Hierarchical linear regression analyses revealed that higher rates of MPAs were
      linked with greater movement abnormalities and salivary cortisol. CONCLUSIONS:
      The findings suggest that MPAs serve as a marker of neurodevelopmental
      abnormalities that affect striatal and hippocampal regions.

PMID- 17188255
TI  - Protecting endothelial function: A novel therapeutic target of ATP-sensitive
      potassium channel openers.

PMID- 17188256
TI  - Induction of primary anti-HIV CD4 and CD8 T cell responses by dendritic cells
      transduced with self-inactivating lentiviral vectors.
AB  - In this study, we demonstrate that a minimal self-inactivating (SIN) lentiviral
      vector (LV) that does not encode any human immunodeficiency virus (HIV) genes is
      able to induce HIV-specific CD4 and CD8 T cell responses after transduction of
      dendritic cells (DCs). The LV-DC-primed T cells displayed HIV-specific lytic
      degranulation, as illustrated by acquisition of CD107a/b expression on the cell
      surface and up-regulation of active caspase 3. HIV-specific cytotoxic T
      lymphocyte (CTL) response was consistently detected using different assays, and T
      cell receptors specific to three prominent HIV epitopes, SL9 (Gag peptide:
      SLYNTVATL), IV9 (Pol peptide: ILKEPVHGV), and MA10 (In peptide: MASDFNLPPV) were
      detected using HLA-A0201 peptide-tetramers. These results demonstrate that DCs
      transduced with the minimal SIN-LV can efficiently induce HIV-specific CD4 and
      CD8 T cell responses. Since LVs are popular gene transfer tools, our results have
      fundamental implications for future LV applications and DC vaccine development.

PMID- 17188257
TI  - Pesticide exposure on southwestern Taiwanese with MnSOD and NQO1 polymorphisms is
      associated with increased risk of Parkinson's disease.
AB  - BACKGROUND: Hypothetic mechanism of the individual vulnerability to oxidative
      stress through metabolism of environmental xenobiotics and genotypic
      polymorphisms has been considered to promote the development of Parkinson's
      disease (PD). In this case-control study, we determined the role of manganese
      containing superoxide dismutase (MnSOD) and NAD(P)H: quinone oxidoreductase 1
      (NQO1) genes in PD risk in a population with high prevalence of pesticide
      exposure. METHODS: From southwestern region of Taiwan, we enrolled 153 patients
      with idiopathic PD and 155 healthy control subjects matched for age, sex and
      origin. Detailed questionnaires of face-to-face interviews among these subjects
      were collected. PCR-based restriction fragment length polymorphism (RFLP) assays
      were used to determine the genotypes of MnSOD (-9 T>C) and NQO1 (609 C>T) genes.
      RESULTS: Exposure to pesticides associated with PD was significant among patients
      with an increased odds ratio (OR) of 1.69 (95%CI, 1.07-2.65), and this
      association remained significant after adjustment for age, sex, and cigarette
      smoking (aOR=1.68, 95%CI, 1.03-2.76, P=0.023). Considering genetic factors, there
      were no significant differences in frequencies of both genotypes of MnSOD and
      NQO1 polymorphisms between PD patients and the control subjects (P>0.05).
      However, this difference in genotype distribution was significant among subjects
      who had been exposed to pesticide, with aOR of 2.49 (95%CI, 1.18-5.26, P=0.0072)
      for MnSOD C allele and aOR of 2.42 (95%CI, 1.16-4.76, P=0.0089) for NQO1 T
      allele, respectively. Moreover, among subjects exposed to pesticide, the combined
      MnSOD/NQO1 variant genotype was significantly associated with a 4.09-fold
      increased risk of PD (95%CI, 1.34-10.64, P=0.0052). CONCLUSION: Susceptible
      variants of MnSOD and NQO1 genes may interact with occupational pesticide
      exposure to increase PD risk in southwestern Taiwanese.

PMID- 17188258
TI  - Preliminary studies of application of CdTe nanocrystals and dextran-Fe3O4
      magnetic nanoparticles in sandwich immunoassay.
AB  - BACKGROUND: The favorable properties of water-soluble CdTe nanocrystals as novel
      biological luminescent label over conventional fluorescent probes have attracted
      considerable interest. The magnetic separation technique has widely been applied
      to various aspects in biotechnology in recent years. In this paper, we made use
      of CdTe nanocrystals and dextran-Fe3O4 magnetic nanoparticles for fluorescence
      immunoassay. METHODS: The CdTe nanocrystals and dextran-Fe3O4 magnetic
      nanoparticles were applied to immunoassay for the determination of human
      immunoglobulin G (HIgG). A rabbit anti-HIgG antibody (primary antibody) was
      immobilized on magnetic nanoparticles, which was used as a solid support. A sheep
      anti-HIgG antibody (secondary antibody) was attached to the surface of the CdTe
      nanocrystals via electrostatic interaction. The immunoassay was based on a
      sandwich immunoreaction of primary antibody on the magnetic nanoparticles, HIgG
      (or serum sample), and the secondary antibody labeled with CdTe nanocrystals.
      RESULTS: The CdTe label was compared with a fluorescein isothiocyanate (FITC)
      label. The CdTe is an order of magnitude more sensitive than the FITC. The
      immunoassay method was applied to determining the HIgG in practical samples and
      the results obtained are in good agreement with those obtained by nephelometry.
      CONCLUSION: This technique may be applied in many types of antibody-antigen
      system.

PMID- 17188259
TI  - Prediction of facial cooling while walking in cold wind.
AB  - A dynamic model of cheek cooling has been modified to account for increased skin
      blood circulation of individuals walking in cold wind. This was achieved by
      modelling the cold-induced vasodilation response to cold as a varying blood
      perfusion term, which provided a source of convective heat to the skin tissues of
      the model. Physiologically-valid blood perfusion was fitted to replicate the
      cheek skin temperature responses of 12 individuals experimentally exposed to air
      temperatures from -10 to 10 degrees C at wind speeds from 2 to 8 ms(-1).
      Resultant cheek skin temperatures met goodness-of-fit criteria and implications
      on wind chill predictions are discussed.

PMID- 17188260
TI  - The roles of Groucho/Tle in left-right asymmetry and Kupffer's vesicle
      organogenesis.
AB  - The heart is the first organ to form and function in the vertebrate embryo.
      Furthermore, differences between the left and right sides of the embryo become
      first detectable during cardiac development. We observed strong cardiac
      laterality phenotypes in medaka embryos by manipulating Groucho protein activity.
      The phenotypes produced by misexpressing Tle4 and the dominant-negative Aes
      reveal a general effect of these corepressor proteins on left-right (LR)
      development. With the help of an inducible expression system, we were able to
      define temporally different phases for these effects. In an early phase during
      gastrulation, Groucho proteins regulate Brachyury expression in the dorsal
      forerunner cells, which later gives rise to the Kupffer's vesicle (KV). The
      interference of endogenous Groucho proteins by misexpression of Aes leads to KVs
      of reduced size, whereas overexpression of Tle4 results in enlarged KVs. The
      expression level of the cilia marker Lrd was also affected both positively and
      negatively from these treatments. In the late phase during somitogenesis, Groucho
      proteins regulate the asymmetric activities of Nodal and Lefty genes. Altering
      canonical Wnt signaling produced similar results in late embryos, however, this
      did not affect KV morphogenesis or Lrd expression in early embryos. Therefore,
      changes in Kupffer's vesicle morphogenesis and the laterality of visceral organs
      following alterations in Groucho corepressor levels demonstrate two distinct
      phases in which Groucho proteins help establish LR asymmetry in medaka fish.

PMID- 17188261
TI  - Cell cycling and differentiation do not require the retinoblastoma protein during
      early Xenopus development.
AB  - The retinoblastoma protein (pRb) is a central regulator of the cell cycle,
      controlling passage through G1 phase. Moreover, pRb has also been shown to play a
      direct role in the differentiation of multiple tissues, including nerve and
      muscle. Rb null mice display embryonic lethality, although recent data have
      indicated that at least some of these defects are due to placental insufficiency.
      To investigate this further, we have examined the role of pRb in early
      development of the frog Xenopus laevis, which develops without the need for a
      placenta. Surprisingly, we see that loss of pXRb has no effect on either cell
      cycling or differentiation of neural or muscle tissue, while overexpression of
      pXRb similarly has no effects. We demonstrate that, in fact, pXRb is maintained
      in a hyperphosphorylated and therefore inactive state early in development.
      Therefore, Rb protein is not required for cell cycle control or differentiation
      in early embryos, indicating unusual control of these G1/G0 events at this
      developmental stage.

PMID- 17188262
TI  - Purinergic signaling regulates neural progenitor cell expansion and neurogenesis.
AB  - Neural stem and progenitor cells typically exhibit a density-dependent survival
      and expansion, such that critical densities are required below which clonogenic
      progenitors are lost. This suggests that short-range autocrine factors may be
      critical for progenitor cell maintenance. We report here that purines drive the
      expansion of ventricular zone neural stem and progenitor cells, and that purine
      receptor activation is required for progenitor cells to be maintained as such.
      Neural progenitors expressed P2Y purinergic receptors and mobilized intracellular
      calcium in response to agonist. Receptor antagonists suppressed proliferation and
      permitted differentiation into neurons and glia in vitro, while subsequent
      removal of purinergic inhibition restored progenitor cell expansion. Real-time
      bioluminescence imaging of extracellular ATP revealed that the source of
      extracellular nucleotides are the progenitor cells themselves, which appear to
      release ATP in episodic burst events. Enzyme histochemistry of the adult rat
      brain for ectonucleotidase activity revealed that NTDPase, which acts to degrade
      active ATP and thereby clears it from areas of active purinergic transmission,
      was selectively localized to the subventricular zone and the dentate gyrus,
      regions in which neuronal differentiation proceeds from the progenitor cell pool.
      These data suggest that purine nucleotides act as proliferation signals for
      neural progenitor cells, and thereby serve as negative regulators of terminal
      neuronal differentiation. As a result, progenitor cell-derived neurogenesis is
      thus associated with regions of both active purinergic signaling and modulation
      thereof.

PMID- 17188263
TI  - Mechanism underlying H2O2-induced inhibition of acetylcholine-induced contraction
      in rabbit tracheal smooth muscle.
AB  - The mechanism underlying the inhibition by H2O2 of acetylcholine-induced
      contraction was investigated in epithelium-denuded strips of rabbit trachea.
      Acetylcholine (10 microM) generated a phasic, followed by a tonic increase in
      both the intracellular Ca2+ concentration ([Ca2+]i) and force. Although the
      acetylcholine-induced tonic contraction was around 9 times the high K+ (80 mM)
      induced one, the two stimulants induced similar [Ca2+]i increases (around 0.2
      microM), indicating that acetylcholine generates tonic contraction via increases
      in both [Ca2+]i and myofilament Ca2+-sensitivity. H2O2 (30 microM) (a) enhanced
      the acetylcholine-induced tonic (not phasic) increase in [Ca2+]i but attenuated
      both phases of the acetylcholine-induced contraction and (b) enhanced the high K+
      induced increase in [Ca2+]i but did not modify the high K+-induced contraction.
      In beta-escin-skinned strips, application of acetylcholine in the presence of GTP
      enhanced the contraction induced by 0.3 microM Ca2+ so that its amplitude became
      similar to that induced by 1 microM Ca2+. H2O2 (30 microM) attenuated the
      contraction induced by 0.3 microM Ca2+ (alone or in the presence of
      acetylcholine) but not those induced by higher concentrations of Ca2+ alone (0.5
      microM and 1 microM). These results indicate that H2O2 acts directly on
      contractile proteins in rabbit tracheal smooth muscle to inhibit the contraction
      induced by low concentrations of Ca2+ (<0.5 microM). An action of H2O2 that
      increases [Ca2+]i (and thereby masks this reactive-oxygen-induced inhibition of
      myofilament Ca2+-sensitivity) is apparent in the presence of high K+ but not of
      acetylcholine. Thus, in rabbit tracheal smooth muscle H2O2 downregulates
      myofilament Ca2+-sensitivity more potently during acetylcholine-induced
      contraction than during high-K+-induced contraction, leading to an effective
      inhibition of the former contraction.

PMID- 17188264
TI  - Involvement of calpain in AMPA-induced toxicity to rat cerebellar Purkinje
      neurons.
AB  - AMPA receptor-elicited excitotoxicity is manifested as both a type of programmed
      cell death termed dark cell degeneration and edematous necrosis, both of which
      are linked to increased intracellular Ca2+ concentration. The appearance of
      marked cytoskeletal changes in response to abusive AMPA receptor activation,
      coupled with increased intracellular Ca2+ concentration suggests activation of
      various destructive enzymes such as calpains, a family of Ca2+-dependent cysteine
      proteases. Since calpains and AMPA have been linked to both necrotic cell death
      and programmed cell death, we sought to determine the role of calpains in
      mediating both types of AMPA-mediated toxicity in Purkinje neurons of the
      cerebellum. These studies employed immunohistochemistry for cytoskeletal
      breakdown products of calpain activity coupled with confocal microscopy and
      pharmacological interventions with calpain and AMPA receptor antagonists. The
      present study identifies an early involvement of calpains in mediating AMPA
      induced dark cell degeneration, but not edematous necrosis, based upon the
      effectiveness of AMPA to generate calpain-derived alpha-spectrin cleavage
      products in cerebellar Purkinje neurons that express dark cell degeneration, and
      the effectiveness of calpain antagonists, PD150606 and MDL28170, to attenuate
      AMPA-induced dark cell degeneration. Moreover, the AMPA receptor antagonist CNQX,
      a proven inhibitor of AMPA-elicited dark cell degeneration, also blocked AMPA
      induced increases in alpha-spectrin, further suggesting interplay between abusive
      AMPA receptor activation, calpain activation and dark cell degeneration. Since
      AMPA-induced dark cell degeneration possesses morphological changes that resemble
      those that occur following brain ischemia in vivo, hypoglycemia, or extended
      seizure episodes, the involvement of calpains as mediators of cell death is
      potentially far reaching and has widespread therapeutic implications in numerous
      CNS disorders.

PMID- 17188266
TI  - Effects of anti-VEGF antibody on blood-brain barrier disruption in focal cerebral
      ischemia.
AB  - Since cerebral ischemia increases expression of vascular endothelial growth
      factor (VEGF) and exogenous VEGF can aggravate BBB disruption in cerebral
      ischemia, we hypothesized that inhibition of endogenous VEGF would attenuate BBB
      disruption. To test this hypothesis, rats were mechanically ventilated with
      isoflurane and a craniotomy (5 mm in diameter) was performed to expose the
      cerebral cortex. Anti-VEGF antibody was applied topically (75 mug) 1 h before
      middle cerebral artery (MCA) occlusion and additional anti-VEGF antibody was
      applied (25 mug) immediately after MCA occlusion (anti-VEGF group). For the
      control animals, normal saline was applied instead of anti-VEGF antibody on the
      surface of the cortex (control group). One hour after MCA occlusion, the transfer
      coefficient (K(i)) of (14)C-alpha-aminoisobutyric acid and volume of (3)H-dextran
      (70,000 Da) distribution were determined to measure the degree of BBB disruption.
      There was no significant difference in vital signs, blood gases, and pericranial
      temperature between the control and the anti-VEGF group. In both of the groups,
      the K(i) of the ischemic cortex (IC) was higher than that of the corresponding
      contralateral cortex (CC) (p<0.05). The K(i) of the IC of the anti-VEGF group was
      significantly lower than that of the IC of the control group (-34%, p<0.05). The
      K(i) of the CC and pons were similar between these two groups. The data of volume
      of dextran distribution followed the same pattern as that of K(i) but without a
      statistical significance. Our data demonstrated that inhibition of endogenous
      VEGF by topical application of anti-VEGF antibody in the ischemic cortex
      decreased the K(i) of (14)C-AIB and suggest that endogenous VEGF is in part
      responsible for the BBB disruption during the early stage of focal cerebral
      ischemia.

PMID- 17188265
TI  - ADP ribosylation factor like 2 (Arl2) protein influences microtubule dynamics in
      breast cancer cells.
AB  - ADP ribosylation factor like 2 (Arl2) protein is involved in the folding of
      tubulin peptides. Variants of the human adenocarcinoma line MCF7 cells with
      increased or reduced content of Arl2 protein were produced and characterized.
      Western blot analysis performed after separation of the different fractions of
      tubulins showed that the content in polymerizable soluble heterodimers was
      significantly increased in cells with the highest Arl2 expression level (MA+) and
      reduced in cells with the lowest Arl2 expression level (MA-) in comparison to
      control cells (MP). Microtubule dynamic instability, measured after
      microinjection of rhodamine-labelled tubulin in living cells, was significantly
      enhanced in MA+ cells and reduced in MA- cells. These alterations involved
      modifications of the microtubule growth and shortening rates, duration of
      attenuation phases, percentage of time spent in each phase (growth, shortening
      and attenuation) and catastrophe frequency. We also observed modifications in the
      expression level of the tumor suppressor protein phosphatase 2Ac, which has been
      shown to form a complex with Arl2. Finally, cell cycle progression was modified
      in these cells, particularly in regard to duration of telophase. In summary,
      alterations in Arl2 protein content were found to be associated with
      modifications in tubulin pools, microtubule dynamics as well as cell cycle
      progression.

PMID- 17188267
TI  - Roles of capsaicin-sensitive primary afferents in differential rat models of
      inflammatory pain: a systematic comparative study in conscious rats.
AB  - To characterize the role of capsaicin-sensitive primary afferents in inflammatory
      pain, the effects of subcutaneous (s.c.) injection of 0.15% capsaicin on
      different chemical irritants-induced pathological nociception including
      persistent spontaneous nociception, primary thermal and mechanical hyperalgesia,
      and inflammatory response were systematically investigated in unanesthetized
      conscious rats. Four different animal models of inflammatory pain: the bee venom
      (BV) test, the formalin test, the carrageenan model, and the complete Freund's
      adjuvant (CFA) model, were employed and compared. Local pre-treatment with
      capsaicin produced a significant inhibition on the s.c. BV and formalin induced
      long-lasting persistent spontaneous nociception. However, this capsaicin-induced
      inhibitory effect on spontaneous nociception in the BV test was only found within
      the late phase (tonic nociception; 11-60 min), but not the early phase (acute
      nociception; 0-10 min). A complete preventing effect of capsaicin on the
      decreased thermal paw withdrawal latency was found in the BV, carrageenan, and
      CFA models. Nevertheless, pre-treatment with capsaicin only produced complete
      blocking effects on the decreased mechanical paw withdrawal threshold in the BV
      and carrageenan models, but not in the CFA model. For inflammatory response, a
      significant inhibition of the BV-elicited paw swelling was found following
      capsaicin treatment. In marked contrast, capsaicin did not produce any effects on
      the paw inflammation during exposure to carrageenan, CFA, and formalin. These
      data suggest that capsaicin-sensitive primary afferents may play differential
      roles in the induction and development of pathological nociception in
      differential inflammatory pain models. In contrast to other chemical irritants,
      BV-induced long-term spontaneous nociception, facilitated nociceptive behavior,
      and inflammation are modulated by peripheral capsaicin-sensitive afferents.

PMID- 17188268
TI  - Transient neuroprotection by minocycline following traumatic brain injury is
      associated with attenuated microglial activation but no changes in cell apoptosis
      or neutrophil infiltration.
AB  - Cerebral inflammation and apoptotic cell death are two processes implicated in
      the progressive tissue damage that occurs following traumatic brain injury (TBI),
      and strategies to inhibit one or both of these pathways are being investigated as
      potential therapies for TBI patients. The tetracycline derivative minocycline was
      therapeutically effective in various models of central nervous system injury and
      disease, via mechanisms involving suppression of inflammation and apoptosis. We
      therefore investigated the effect of minocycline in TBI using a closed head
      injury model. Following TBI, mice were treated with minocycline or vehicle, and
      the effect on neurological outcome, lesion volume, inflammation and apoptosis was
      evaluated for up to 7 days. Our results show that while minocycline decreases
      lesion volume and improves neurological outcome at 1 day post-trauma, this
      response is not maintained at 4 days. The early beneficial effect is likely not
      due to anti-apoptotic mechanisms, as the density of apoptotic cells is not
      affected at either time-point. However, protection by minocycline is associated
      with a selective anti-inflammatory response, in that microglial activation and
      interleukin-1beta expression are reduced, while neutrophil infiltration and
      expression of multiple cytokines are not affected. These findings demonstrate
      that further studies on minocycline in TBI are necessary in order to consider it
      as a novel therapy for brain-injured patients.

PMID- 17188269
TI  - Reproduction and embryonic diapause in a marsupial: insights from captive female
      Honey possums, Tarsipes rostratus (Tarsipedidae).
AB  - The reproductive physiology of the polyoestrous Honey possum (Tarsipes rostratus)
      is virtually unknown except that it shares with the kangaroos and wallabies the
      phenomenon of embryonic diapause. Its tiny size necessitates an alternate
      approach to study their reproductive cycle. We have accordingly utilised faecal
      steroid analysis. Baseline faecal cortisol levels in the Honey possum, at 4.1+/
      0.3 mug g-1, are approximately 100-fold those of other mammals and are associated
      with adrenal glands that, on a mass-specific basis, are almost 10 times larger
      than the adrenals of other mammalian, including marsupial, species. Histological
      examination of the adrenal glands revealed no abnormalities, however, but their
      hypertrophy and the peaks recorded in faecal levels following disturbance suggest
      that the Honey possum is vulnerable to chronic stressors in the captive
      situation. Mean faecal progestagens (124.4+/-107.3 ng g-1) and oestradiol-17beta
      (4.1+/-1.1 ng g-1) in 4 non-pregnant females maintained long term were not
      different from those of 5 pregnant females (101.4+/-61.0 ng g-1 and 4.3+/-1.5 ng
      g-1, respectively) and, on analysis, revealed a cyclicity of 24+/-1.2 days. We
      would predict from this evidence that the gestation period, in the absence of
      lactation, is approximately 23 days. Four of the pregnant females, monitored from
      July to November under conditions of 10:14 L:D photoperiod, showed a fall in
      levels of progestagens from 175.9+/-10.8 ng g-1 in July and August to 30.9+/-9.4
      ng g-1 in October, while mean faecal levels of oestradiol-17beta increased from
      3.8+/-0.4 ng g-1 in July to 5.7+/-0.3 ng g-1 in October. September and October
      are months of peak reproductive activity in the wild and we suggest that these
      hormonal modulations may represent an entrained reproductive rhythm. Blastocysts
      appear to develop at varying rates, both within the one uterus, and between the
      two uteri of a single female. In addition, the time taken to reach the blastocyst
      stage may be longer than in any other marsupial studied to date. An association
      of the age of the pouch young with the stage reached by the developing blastocyst
      does not support the conclusion that blastocysts, once formed, grow slowly during
      lactation or diapause. Contrary to previous reports, we have documented what
      appears to be a lactational inhibition on blastocysts in diapause and have
      estimated the length of the 'delayed' reproductive cycle in two females as less
      than 2 weeks. Reactivation of blastocysts in Tarsipes has been shown to be
      stimulated by shortening day lengths after the summer solstice, a response
      similar to the annual breeding period of macropodid marsupials. Results from
      studying Honey possums in captive conditions suggest that the control of diapause
      in Tarsipes appears to be three-fold; lactational, photoperiodic and an entrained
      rhythm.

PMID- 17188270
TI  - Measurement of fish steroids in water--a review.
AB  - Measurement of fish steroids in water provides a non-invasive alternative to
      measurement in blood samples, offering the following advantages: zero or minimal
      intervention (i.e. no anaesthetic, bleeding or handling stress); results not
      being biased by sampling stress; repeat measurements on the same fish; the
      possibility of making non-lethal measurements on small and/or rare fish;
      integrating the response of many (or of single) fish; and allowing concurrent
      monitoring of behaviour or physiology. The procedure is relatively new and,
      although applications are still fairly limited, there are several themes and
      potential problem areas that are worthy of review.

PMID- 17188271
TI  - Third-trimester erythrocytapheresis in pregnant patients with sickle cell
      disease.
AB  - OBJECTIVE: To evaluate the effects of prophylactic transfusion by means of
      erythrocytapheresis at the beginning of the third trimester of pregnancy in women
      with sickle cell disease (SCD). METHODS: A cohort of 14 pregnant women with SCD
      who received prophylactic erythrocytapheresis transfusions at the beginning of
      the third trimester was retrospectively compared with a cohort of 17 pregnant
      women who received simple prophylactic transfusions for no indication other than
      SCD severity. RESULTS: Prophylactic erythrocytapheresis transfusions were
      associated with a lower risk of intrauterine growth restriction (OR, 0.11; 95%
      confidence interval, 0.01-1.00) and oligohydramnios (OR, 0.65; 95% confidence
      interval, 0.45-0.92) in pregnant women with SCD. CONCLUSION: These results
      suggest that erythrocytapheresis transfusions are beneficial in women with SCD
      who are in the third trimester of pregnancy. Given the decrease in transfusion
      risks, this therapy deserves further evaluation in future trials.

PMID- 17188272
TI  - Laparoscopic uterine artery occlusion versus uterine fibroid embolization.

PMID- 17188273
TI  - Clusters of eclampsia in a Nigerian teaching hospital.
AB  - OBJECTIVE: To describe the pattern of eclampsia between 1995 and 2004 at the
      Usmanu Danfodiyo University Teaching Hospital, Sokoto, northwestern Nigeria.
      STUDY DESIGN: A retrospective cohort of all deliveries and eclamptics seen from
      1st January 1995 to 31st December 2004. Clusters of eclampsia were identified
      using purely temporal scan statistics. RESULTS: Of 15,318 deliveries during the
      period, 657(4.29%) had eclampsia. The yearly incidence of eclampsia at the
      beginning of the study period (1995) was 0.39% but this had increased to 7.0% in
      2004 at a background exponential rate best described by quadratic curve fitting
      prediction model and a forecast curve that predicts an incidence of eclampsia of
      at least 32.4% of total deliveries by 2009. Temporal clusters occurred in 1996,
      2001 and 2003-2004. CONCLUSION: The incidence of eclampsia is unusually high and
      is increasing. It has shown 3 clusters in the last 10 years.

PMID- 17188274
TI  - Diversity of trematode genetic clones within amphipods and the timing of same
      clone infections.
AB  - The genetic diversity of trematodes within second intermediate hosts has
      important implications for the evolution of trematode populations as these hosts
      are utilized after the parasites reproduce asexually within first intermediate
      hosts and before sexual reproduction within definitive hosts. We characterised
      the genetic clonal diversity of the marine trematode Maritrema novaezealandensis
      within amphipod (Paracalliope novizealandiae) second intermediate hosts using
      four to six microsatellite loci to determine if multiple copies of identical
      trematode clones existed within naturally infected amphipods. To determine the
      relative timing of infections by identical clones within hosts, trematode
      metacercariae were assigned to six developmental stages and the stages of
      identical clones were compared. The genotypes of 306 trematodes were determined
      from 44 amphipods each containing more than one trematode. Six pairs of identical
      trematode clones were recovered in total (representing five amphipods: 11% of
      amphipods with greater than one trematode) and all pairs of clones belonged to
      the same developmental stage. This suggests that identical clone infections are
      effectively synchronous. A general decrease in the number of metacercariae
      recovered, prevalence, and mean intensity of infection for each subsequent
      developmental stage coupled with large numbers of metacercariae (>9) only being
      recovered from recent infections, supports the occurrence of post-infection
      amphipod mortality and/or within-host trematode mortality. Taken together, our
      results indicate that natural infections are characterised by high genetic
      diversity, but that amphipods also periodically encounter "batches" of
      genetically identical clones, potentially setting the stage for interactions
      within and between clonal groups inside the host.

PMID- 17188275
TI  - Expression of vasa (vas)-related genes in germ cells and specific interference
      with gene functions by double-stranded RNA in the monogenean, Neobenedenia
      girellae.
AB  - Neobenedenia girellae, a monogenean, is an important pathogen in marine cultured
      fish such as yellowtail and amberjack. An effective control method is required
      but none has yet been established. Aiming to establish a new control method by
      interfering with the gametogenesis of N. girellae, we focused on vasa (vas)
      related genes that are expressed exclusively in the germline granules in
      Drosophila, Caenorhabditis elegans and other animals. Three vas-related genes (N.
      girellae vasa-like gene, Ngvlg1, Ngvlg2 and Ngvlg3) were isolated by PCR and
      Ngvlg1 and Ngvlg2 were shown to be expressed only in germ cells. We demonstrated
      that introduction of double-stranded Ngvlg1 or Ngvlg2 RNA by soaking resulted in
      partial or complete loss of germ cells. Moreover, the hatching rate of eggs from
      animals showing partial loss of germ cells decreased significantly. These results
      suggest that Ngvlg1 and Ngvlg2 are essential genes for germ cell quantity and
      quality. The possibility that a new control method can be developed by
      controlling gametogenesis of N. girellae was proven, because sterilised N.
      girellae could be produced.

PMID- 17188276
TI  - The role of sex in parasite dynamics: model simulations on transmission of
      Heligmosomoides polygyrus in populations of yellow-necked mice, Apodemus
      flavicollis.
AB  - We investigated possible mechanisms that could cause sex-biased parasite
      transmission of the helminth Heligmosomoides polygyrus in its rodent host,
      Apodemus flavicollis, using a modelling approach. Two, not mutually exclusive,
      hypotheses were examined: that sex-biased parasite transmission is caused by
      differences in immunity that influence the success of free-living stages and/or
      is caused by sex differences in host behaviour and the dissemination of infective
      stages. Model simulations were compared with results from a field manipulation
      experiment of H. polygyrus in replicated populations of A. flavicollis.
      Simulations predicted the experimental field results, and both hypotheses
      explained the pattern observed. Transmission is male-biased if a male immune
      response increases fertility, hatching or survival of free-living stages.
      Alternatively, transmission is male-biased if their behavioural characteristics
      allow them to spread infective larvae in areas more frequently used by females.
      These results highlight that host sex is not only responsible for differences in
      parasite susceptibility, but may profoundly influence host-parasite interactions,
      resulting in a sex bias in parasite transmission.

PMID- 17188277
TI  - Natural killer cells act as early responders in an experimental infection with
      Neospora caninum in calves.
AB  - The intracellular protozoan parasite Neospora caninum is a cause of abortion and
      congenital disease in cattle worldwide. We have previously shown that natural
      killer (NK) cells produce IFN-gamma in response to N. caninum tachyzoites in
      vitro. This study aimed to investigate the role of NK cells and other cellular
      immune responses in an experimental N. caninum infection model in calves.
      Phenotyping of peripheral blood lymphocytes showed a drop in the percentage of NK
      cells at days 4-6 after i.v. inoculation, followed by an increase in the
      percentage of both NK cells and CD8+ T cells which peaked at days 11-15. A whole
      blood flow cytometric assay showed that CD4+ T cells were the major IFN-gamma
      producing cells, but in the early stages of the infection both NK cells and CD8+
      T cells contributed to IFN-gamma production. We also compared the ability of two
      different N. caninum antigen preparations--sonicated soluble antigens and intact
      heat-inactivated parasites--to induce proliferation and IFN-gamma production in
      various cell types. Heat-inactivated tachyzoites induced a 3.7 times greater
      increase in the number of IFN-gamma producing NK cells compared with sonicated
      soluble antigens. This indicated the presence of some NK cell-stimulating
      antigens in the intact tachyzoite that were absent from the sonicated soluble
      antigens. The heat-inactivated whole tachyzoites also inhibited gammadelta T cell
      proliferation while the soluble antigens from N. caninum did not. We believe this
      is the first time NK cells have been demonstrated to be early responders in N.
      caninum infection in calves.

PMID- 17188278
TI  - Initiation of inflammation and cell death during liver abscess formation by
      Entamoeba histolytica depends on activity of the galactose/N-acetyl-D
      galactosamine lectin.
AB  - The parasite Entamoeba histolytica colonizes the human intestine causing amoebic
      colitis and disseminates through the vascular route to form liver abscesses. The
      Gal/GalNAc lectin is an adhesion protein complex which sustains tissue invasion
      by E. histolytica. Disruption of the Gal/GalNAc lectin function in engineered
      parasites (HGL-2 trophozoites) changed the pathophysiology of hamster liver
      abscess formation. HGL-2 trophozoites produced numerous small inflammatory foci
      located in the vicinity of blood vessels. The low penetration of HGL-2
      trophozoites into hepatic tissue was shown to be associated with weak attraction
      of neutrophils and macrophages to the infiltrated areas and absence of pro
      inflammatory tumour necrosis factor, in contrast to wild type or control vector
      infections. The low host inflammatory response in HGL-2 infections correlated
      with a delay in apoptosis of hepatic cells, whereas apoptosis of endothelial
      cells was not detected. Triggering of apoptosis in both host cell types most
      likely has a central role in modulating inflammation, a major landmark in hepatic
      amoebiasis. These data highlight the key role of the Gal/GalNAc lectin in
      initiation of E. histolytica hepatic infection.

PMID- 17188279
TI  - Theoretical model and experimental study of red blood cell (RBC) deformation in
      microchannels.
AB  - The motion and deformation of red blood cells (RBCs) flowing in a microchannel
      were studied using a theoretical model and a novel automated rheoscope. The
      theoretical model was developed to predict the cells deformation under shear as a
      function of the cells geometry and mechanical properties. Fluid dynamics and
      membrane mechanics are incorporated, calculating the traction and deformation in
      an iterative manner. The model was utilized to evaluate the effect of different
      biophysical parameters, such as: inner cell viscosity, membrane shear modulus and
      surface to volume ratio on deformation measurements. The experimental system
      enables the measurement of individual RBCs velocity and their deformation at
      defined planes within the microchannel. Good agreement was observed between the
      simulation results, the rheoscope measurements and published ektacytometry
      results. The theoretical model results imply that such deformability measuring
      techniques are weakly influenced by changes in the inner viscosity of the cell or
      the ambient fluid viscosity. However, these measurements are highly sensitive to
      RBC shear modulus. The shear modulus, estimated by the model and the rheoscope
      measurements, falls between the values obtained by micropipette aspiration and
      laser trapping. The study demonstrates the integration of a theoretical model
      with a microfabricated device in order to achieve a better understanding of RBC
      mechanics and their measurement using microfluidic shear assays. The system and
      the model have the potential of serving as quantitative clinical tools for
      diagnosing deformability disorders in RBCs.

PMID- 17188281
TI  - Rapid headspace solid-phase microextraction/gas chromatographic/mass
      spectrometric assay for the quantitative determination of some of the main
      odorants causing off-flavours in wine.
AB  - In this study we present a rapid and simultaneous assay method using headspace
      (HS) solid-phase microextraction (SPME)/gas chromatography (GC)/electron impact
      (EI) mass spectrometry (MS) (selected ion monitoring) for contaminants causing
      the principal organoleptic defects of wine (2,4,6-trichloroanisole, 2,3,4,6
      tetrachloroanisole, pentachloroanisole, 2,4,6-tribromoanisole, 1-octen-3-ol,
      geosmin, 2-methylisoborneol, 3-isopropyl-2-methoxypyrazine, fenchol, fenchone, 2
      methoxy-3,5-dimethylpyrazine, 4-ethylphenol, 4-ethylguaiacol, 4-vinylphenol, 4
      vinylguaiacol, 3-isobutyl-2-methoxypyrazine, guaiacol and ethyl acetate). The
      method was validated according to protocols NF ISO 5725-1, 2 and NF V03-110. Its
      characteristics (limit of detection (LOD), limit of quantification (LOQ),
      uncertainties) were determined after having optimised the SPME parameters. The
      target contaminants were quantified in the wines below their threshold of
      perception with a satisfactory relative standard deviation for all the analytes
      except ethyl acetate (RSD=36%); for that, the assay method permits clear
      differentiation of the wines that are at risk of presenting an acescent
      character, i.e. containing more than 120mgL(-1) ethyl acetate. The target
      volatile and odorous substances were determined at concentrations significantly
      below their threshold of perception in a hydroalcoholic context and their
      threshold of recovery in wines.

PMID- 17188280
TI  - Sensitive determination of erythrosine and other red food colorants using
      capillary electrophoresis with laser-induced fluorescence detection.
AB  - Capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) was
      applied to separation and sensitive determination of red food colorants. Diode
      pumped frequency-doubled Nd:YAG laser (532 nm) was used as an excitation source
      in a laboratory-built CE-LIF system. For highly fluorescent erythrosine B (E127),
      an extrapolated limit of detection (LOD) of 0.4 ng mL(-1) (S/N=3) was achieved.
      Extrapolated LODs of other tested red additives, such as carmoisine, E122 (0.5
      microg mL(-1)); amaranth, E123 (0.2 microg mL(-1)); ponceau 4R, E124 (0.3 microg
      mL(-1)) and red 2G, E128 (0.3 microg mL(-1)) were about one-order lower compared
      to results obtained with CE with absorbance detection in UV/vis (CE-UV/vis). The
      main advantages of using CE-LIF for analysis of food samples are high selectivity
      and minimization of matrix effect. To our knowledge, this is the first use of CE
      LIF for determination of red food colorants.

PMID- 17188282
TI  - Study of molar response of dextrans in electrochemical detection.
AB  - In this work, a methodological approach is reported, aimed at assessing the
      electrochemical response of some model gluco-oligosaccharides (dextrans). Such
      strategy is based on the complementary use of both anion-exchange chromatography
      with pulsed amperometric detection (HPAEC-PAD) and capillary zone electrophoresis
      coupled with UV detection (CZE-UV). Unlike HPAEC-PAD, CZE-UV required
      derivatization with a chromophoric dye (i.e., 8-aminonaphtalene-1,3,6
      trisulphonic acid, ANTS) to enhance UV response and separation selectivity. From
      the comparison between chromophore response and PAD signal, the reliability of
      HPAEC-PAD for quantitative evaluation of dextran mixtures containing mainly
      oligomers with polymerization degree (DP) up to 18 could be proved, due to the
      fairly constant molar response. For higher DPs (up to 41), a maximum in the trend
      of the molar responses was observed followed by a steep decrease for DPs higher
      than about 30-35; indeed, an underestimation of weight-average molecular weight
      of dextran mixtures containing such oligomers was noticed.

PMID- 17188283
TI  - Determination of pesticides in water by cone-shaped membrane protected liquid
      phase microextraction prior to micro-liquid chromatography.
AB  - A new sample pre-treatment technique termed cone-shaped membrane liquid phase
      microextraction (CSM-LPME) was developed and combined with micro-liquid
      chromatography (micro-LC) for the determination of selected pesticides in water
      samples. Four pesticides (hexaconazole, procymidone, quinalphos and vinclozolin)
      were considered as target analytes. Several important extraction parameters such
      as types of extraction solvent, agitation rate, pH value, total exposure time and
      effect of salt and humic acids were optimized. Enrichment factors of > 50 folds
      were easily achieved within 20 min of extraction. The analytical data
      demonstrated relative standard deviations for the reproducibility of the
      optimized CSM-LPME method ranging from 6.3 to 7.5%. The correlation coefficients
      of the calibration curves were at least 0.9995 across a concentration range of 2
      100 microg/L. The detection limits for all the analytes were found to be in the
      range of 1.1-1.9 microg/L.

PMID- 17188284
TI  - Biphasic aqueous organometallic catalysis promoted by cyclodextrins: can surface
      tension measurements explain the efficiency of chemically modified cyclodextrins?
AB  - Methylated and hydroxypropylated cyclodextrins (CDs) are highly efficient mass
      transfer promoters in biphasic aqueous organometallic processes. The surface
      tension measurements demonstrated that these CDs adsorb at air-water interface
      and allowed to determine surface excess of CD by using Gibbs adsorption equation.
      Interestingly, a good correlation between surface excess and catalytic activity
      was obtained in the case of hydroformylation and Tsuji-Trost reactions. These
      results point out the importance of CD adsorption at the interface in biphasic
      aqueous organometallic processes.

PMID- 17188285
TI  - Molecular behavior and synergistic effects between sodium dodecylbenzene
      sulfonate and Triton X-100 at oil/water interface.
AB  - Significant synergistic effects between sodium dodecylbenzene sulfonate (SDBS)
      and nonionic nonylphenol polyethylene oxyether, Triton X-100 (TX-100), at the
      oil/water interface have been investigated by experimental methods and computer
      simulation. The influences of surfactant concentration, salinity, and the ratio
      of the two surfactants on the interfacial tension were investigated by
      conventional interfacial tension methods. A dissipative particle dynamics (DPD)
      method was used to simulate the adsorption properties of SDBS and TX-100 at the
      oil/water interface. The experiment and simulation results indicate that ultralow
      (lower than 10(-3) mN m(-1)) interfacial tension can be obtained at high salinity
      and very low surfactant concentration. Different distributions of surfactants in
      the interface and the bulk solution corresponding to the change of salinity have
      been demonstrated by simulation. Also by computer simulation, we have observed
      that either SDBS or TX-100 is not distributed uniformly over the interface.
      Rather, the interfacial layer contains large cavities between SDBS clusters
      filled with TX-100 clusters. This inhomogeneous distribution helps to enhancing
      our understanding of the synergistic interaction of the different surfactants.
      The simulation conclusions are consistent with the experimental results.

PMID- 17188286
TI  - Nanostructured Cu(x)Ce1-xO2-y mixed oxide catalysts: characterization and WGS
      activity tests.
AB  - Cu(x)Ce(1-x)O(2-y) mixed oxide catalysts were prepared by different preparation
      procedures: co-precipitation, the sol-gel peroxide route, and the sol-gel citric
      acid-assisted route. The resulting solids were investigated by means of XRD, BET,
      H(2) and CO temperature-programmed reduction (TPR), oxidation (TPO) and
      desorption (TPD) analyses, and N(2)O pulse selective reaction. It was confirmed
      that H(2) (CO) consumed for complete reduction of well-dispersed and bulk-like
      CuO phases to Cu(0), reduction of surface ceria and H(2) (CO) adsorption on the
      catalyst surface contribute to the total H(2) (CO) consumption. Among catalysts
      examined, the Cu(0.15)Ce(0.85)O(2-y) mixed oxide sample prepared by means of co
      precipitation method exhibits the highest activity and stability for water-gas
      shift (WGS) pulse reaction in the range of employed operating conditions. WGS
      activity of copper-ceria mixed oxide catalysts is determined by the extent of
      surface ceria reduction and dispersion of copper species.

PMID- 17188287
TI  - Instability of a two-layer thin liquid film with surfactants: Dewetting waves.
AB  - Dewetting dynamics of a liquid film composed of two superposed ultra-thin layers
      of immiscible liquids resting on a solid substrate is investigated in the case
      when surfactants are present at the liquid-liquid interface. Two cases are
      considered: insoluble surfactant and surfactant soluble in the lower liquid. The
      dependence of Hamaker constants on the surfactant concentration is taken into
      account. A system of three strongly nonlinear evolution equations describing
      large (comparable to the layer thicknesses), long-wave perturbations of the
      liquid-liquid and liquid-gas interfaces, as well as the surfactant concentration,
      is derived for each case in the lubrication approximation. The linear stability
      analysis shows that in the presence of surfactants, oscillatory dewetting
      instability can occur. Numerical simulations of this system of nonlinear
      evolution equations are performed. It is found that in the case of oscillatory
      instabilities, the system exhibits either standing or traveling "dewetting
      waves." The weakly nonlinear analysis explains this phenomenon.

PMID- 17188288
TI  - A novel cetyltrimethyl ammonium silver bromide complex and silver bromide
      nanoparticles obtained by the surfactant counterion.
AB  - A novel cetyltrimethyl ammonium silver bromide (CTASB) complex has been prepared
      simply through the reaction of silver nitrate with cetyltrimethyl ammonium
      bromide (CTAB) in aqueous solution at room temperature by controlling the
      concentration of CTAB and the molar ratio of CTAB to silver nitrate in the
      reaction solution, in which halogen in CTAB is used as surfactant counterion. The
      structure and thermal behavior of cetyltrimethyl ammonium silver bromide have
      been investigated by using X-ray diffraction (XRD), infrared spectroscopy (IR), X
      ray photoelectron spectroscopy (XPS), UV/vis spectroscopy, thermal analysis (TG
      DTA), transmission electron microscopy (TEM), and scanning electron microscopy
      (SEM). The results show that the complex possesses a metastable layered
      structure. Upon heating the CTASB aqueous dispersion to above 80 degrees C, the
      structure change of the complex took place and CTAB-capped nanosized silver
      bromide particles further formed.

PMID- 17188289
TI  - Surface complexes of phthalic acid at the hematite/water interface.
AB  - The adsorption of o-phthalic acid at the hematite/water interface was
      investigated experimentally using batch adsorption experiments and attenuated
      total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy over a wide
      range of solution pH, surface loading, and ionic strength conditions. Molecular
      orbital calculations for several possible surface complexes were also performed
      to assign atomistic structures to the features observed in the ATR-FTIR spectra.
      The results of the batch adsorption experiments exhibit typical anionic
      characteristics with high adsorption at low pH and low adsorption at high pH. The
      adsorption of phthalic acid also exhibits a strong dependence on ionic strength,
      which suggests the presence of outer-sphere complexes. ATR-FTIR spectra provide
      evidence of three fully deprotonated phthalate surface complexes (an outer-sphere
      complex and two inner-sphere complexes) under variable chemical conditions. A
      fully deprotonated outer-sphere complex appears to dominate adsorption in the
      circumneutral pH region, while two fully deprotonated inner-sphere complexes that
      shift in relative importance with surface coverage increase in importance at low
      pH. Comparison of experimental and theoretical calculations suggests the two
      inner-sphere complexes are best described as a mononuclear bidentate (chelating)
      complex and a binuclear bidentate (bridging) complex. The mononuclear bidentate
      inner-sphere complex was favored at relatively low surface coverage. With
      increasing surface coverage, the relative contribution of the binuclear bidentate
      inner-sphere complex increased in importance.

PMID- 17188290
TI  - Protein transduction as a means of effective manipulation of Cdc42 activity in
      primary T cells.
AB  - The Rho family GTPase Cdc42 is a critical regulator of cellular polarization from
      yeast to man. An analysis of its function in T cell activation is therefore of
      interest. This analysis poses two substantial challenges, similar to the analysis
      of many other critical T cell signaling intermediates. First, Cdc42 is required
      for development and cell survival, necessitating short-term manipulation of its
      activity. Second, Cdc42 is likely involved in multiple signaling pathways,
      requiring approaches to distinguish multiple roles. To address these challenges,
      we first determined and quantified spatio-temporal patterns of Cdc42 activity
      using live cell video fluorescence microscopy. This generates hypotheses at which
      times and locations Cdc42 might play possibly distinct roles. Second and as the
      focus of this manuscript, we employed protein transduction to manipulate Cdc42
      activity for the generation of causality. Protein transduction allows such
      manipulation to be short-term, quantitative, and with multiple reagents. Here, we
      characterize uptake, retention, and subcellular distribution of protein
      transduction reagents. We describe how a more quantitative single cell analysis
      of Cdc42 activity provides superior distinction between experimental conditions.
      And we show how we have used dose responses of the protein transduction reagents
      to minimize side effects while retaining efficacy. We suggest that our strategy
      is an important complement to more established techniques to study protein
      function in primary T cells, in particular in the investigation of signaling
      intermediates that are essential for cell survival and regulate multiple aspects
      of T cell activation.

PMID- 17188291
TI  - Infection of Harmonia axyridis (Coleoptera: Coccinellidae) by Hesperomyces
      virescens (Ascomycetes: Laboulbeniales): role of mating status and aggregation
      behavior.
AB  - The ectoparasitic fungus Hesperomyces virescens was studied on Harmonia axyridis
      in North Carolina, in the southeastern United States. A primary goal was to
      investigate transmission of the disease by examining the correlation between the
      pattern of fungal infection and seasonal change in host behavior. Beetles were
      collected as they arrived at their winter quarters at two sites; in one site they
      were also subsampled at mid- and late winter. Insects were sexed and weighed,
      fungal thalli were counted, and their location on the host body mapped;
      spermathecae of females were examined for sperm. Infection levels varied between
      sites, differed significantly between the sexes in one site but not the other,
      and increased by approximately 40% during winter. The distribution of thalli on
      the body changed seasonally, in concert with behavioral changes in the host. At
      fall flight, thalli were found most often on the posterior elytra of mated
      females, virgin females, and males. This is suggestive that the disease had been
      spread among both sexes via successful and failed copulation attempts; however,
      the relatively low incidence of infection on the male venter does not fit the
      sexual transmission scenario. During winter, thallus location shifts in concert
      with beetle aggregation behavior, with infections more often located on the head
      and legs. Fresh weight of beetles decreased by approx. 20% during winter, but was
      not affected by disease status. Prior to spring flight, uninfected females were
      preferred as mating partners, but the probable relationship between female age
      and infection status complicates interpretation of the data.

PMID- 17188292
TI  - Cardiac pacemaker cell failure with preserved I(f), I(CaL), and I(Kr): a lesson
      about pacemaker function learned from ischemia-induced bradycardia.

PMID- 17188293
TI  - Regulation of voltage-gated cardiac sodium current by epidermal growth factor
      receptor kinase in guinea pig ventricular myocytes.
AB  - Voltage-gated cardiac fast sodium channel current (I(Na)) plays a critical role
      in the initiation and propagation of the myocardial action potential, and
      regulation of cardiac I(Na) by protein tyrosine kinases (PTKs) is not well
      documented, though it is known that ion channels are among the targets of PTKs.
      The present study was therefore designed to investigate whether/how cardiac I(Na)
      was modulated by PTKs in guinea pig ventricular myocytes using whole-cell patch
      clamp and immunoprecipitation and Western blotting approaches. It was found that
      cardiac I(Na) was enhanced by epidermal growth factor (EGF), and the effect was
      antagonized by the selective epidermal growth factor receptor (EGFR) kinase
      inhibitor tyrphostin AG556 while potentiated by orthovanadate (a protein tyrosine
      phosphatase (PTP) inhibitor). In addition, AG556 inhibited, while orthovanadate
      increased I(Na), and the inhibition of I(Na) by AG556 was antagonized by
      orthovanadate. Immunoprecipitation and Western blotting analysis demonstrated
      that tyrosine phosphorylation level of cardiac sodium channels was enhanced by
      EGF or orthovanadate, and reduced by AG556. The AG556-induced reduction of
      phosphorylation level was significantly reversed by orthovanadate. Our results
      demonstrate the novel information that EGFR kinase enhances, and PTPs reduce
      native cardiac I(Na) in guinea pig ventricular myocytes.

PMID- 17188294
TI  - Intermittent hypoxia-induced delayed cardioprotection is mediated by PKC and
      triggered by p38 MAP kinase and Erk1/2.
AB  - We previously reported that acute intermittent hypoxia (IH) confers delayed
      cardioprotection against a prolonged ischemic insult in the rat, via the
      involvement of nitric oxide synthase and K(ATP) channels. In the present study,
      we investigated the role of protein kinase C (PKC), phosphatidylinositol-3-kinase
      (PI3K), stress activated p38 MAP kinase (MAPK) and extracellular signal-regulated
      kinase (ERK1/2) using selective inhibitors of these pathways. Adult male rats
      were exposed to 1-min cycles of IH (10% O(2), 40 s)/normoxia (21% O(2), 20 s)
      during 4 h or to normoxic cycles. 24 h later, isolated hearts were perfused in
      Langendorff mode and subjected to a 30-min global ischemia followed by 120 min of
      reperfusion. Compared to normoxic conditions, IH significantly reduced infarct
      size (22.2+/-2.4% vs. 33.8+/-2.6%, p<0.05), improved coronary flow and decreased
      the contracture at reperfusion. When administered before sustained ischemia,
      chelerythrine (a PKC inhibitor) abolished both the IH-induced reduction in
      infarct size (36.1+/-4.9%) and improvement in hemodynamic parameters. In
      contrast, chelerythrine administration 10 min before IH, did not modify the
      delayed cardioprotective response. Similarly, wortmannin (a PI3K inhibitor)
      administration 10 min before IH was unable to block the cardioprotective effects.
      However, administration of SB203580 (a p38 MAPK inhibitor) and PD98059 (an Erk1/2
      inhibitor), 30 min before IH abolished its delayed infarct-sparing effect (32.2+/
      3.4% and 33.9+/-2.9%, respectively). In addition, 24 h after IH, a significant
      increase in p38 MAPK and Erk1/2 phosphorylation was observed by Western blot.
      These results suggest that the delayed preconditioning induced by intermittent
      hypoxia does not involve the PI3K signalling pathway and that is mediated by PKC
      and triggered by p38 MAPK and Erk1/2.

PMID- 17188296
TI  - Diffusional barrier in the unfolding of a small protein.
AB  - To determine how the dynamics of the polypeptide chain in a protein molecule are
      coupled to the bulk solvent viscosity, the unfolding by urea of the small protein
      barstar was studied in the presence of two viscogens, xylose and glycerol.
      Thermodynamic studies of unfolding show that both viscogens stabilize barstar by
      a preferential hydration mechanism, and that viscogen and urea act independently
      on protein stability. Kinetic studies of unfolding show that while the rate
      limiting conformational change during unfolding is dependent on the bulk solvent
      viscosity, eta, its rate does not show an inverse dependence on eta, as expected
      by Kramers' theory. Instead, the rate is found to be inversely proportional to an
      effective viscosity, eta + xi, where xi is an adjustable parameter which needs to
      be included in the rate equation. xi is found to have a value of -0.7 cP in
      xylose and -0.5 cP in glycerol, in the case of unfolding, at constant urea
      concentration as well as under isostability conditions. Hence, the unfolding
      protein chain does not experience the bulk solvent viscosity, but instead an
      effective solvent viscosity, which is lower than the bulk solvent viscosity by
      either 0.7 cP or 0.5 cP. A second important result is the validation of the
      isostability assumption, commonly used in protein folding studies but hitherto
      untested, according to which if a certain concentration of urea can nullify the
      effect of a certain concentration of viscogen on stability, then the same
      concentrations of urea and viscogen will also not perturb the free energy of
      activation of the unfolding of the protein.

PMID- 17188295
TI  - Alternative conformations at the RNA-binding surface of the N-terminal U2AF(65)
      RNA recognition motif.
AB  - The essential pre-mRNA splicing factor, U2 auxiliary factor 65KD (U2AF(65))
      recognizes the polypyrimidine tract (Py-tract) consensus sequence of the pre-mRNA
      using two RNA recognition motifs (RRMs), the most prevalent class of eukaryotic
      RNA-binding domain. The Py-tracts of higher eukaryotic pre-mRNAs are often
      interrupted with purines, yet U2AF(65) must identify these degenerate Py-tracts
      for accurate pre-mRNA splicing. Previously, the structure of a U2AF(65) variant
      in complex with poly(U) RNA suggested that rearrangement of flexible side-chains
      or bound water molecules may contribute to degenerate Py-tract recognition by
      U2AF(65). Here, the X-ray structure of the N-terminal RRM domain of U2AF(65)
      (RRM1) is described at 1.47 A resolution in the absence of RNA. Notably, RNA
      binding by U2AF(65) selectively stabilizes pre-existing alternative conformations
      of three side-chains located at the RNA interface (Arg150, Lys225, and Arg227).
      Additionally, a flexible loop connecting the beta2/beta3 strands undergoes a
      conformational change to interact with the RNA. These pre-existing alternative
      conformations may contribute to the ability of U2AF(65) to recognize a variety of
      Py-tract sequences. This rare, high-resolution view of an important member of the
      RRM class of RNA-binding domains highlights the role of alternative side-chain
      conformations in RNA recognition.

PMID- 17188297
TI  - A type IV modification dependent restriction nuclease that targets glucosylated
      hydroxymethyl cytosine modified DNAs.
AB  - The Escherichia coli CT596 prophage exclusion genes gmrS and gmrD were found to
      encode a novel type IV modification-dependent restriction nuclease that targets
      and digests glucosylated (glc)-hydroxymethylcytosine (HMC) DNAs. The protein
      products GmrS (36 kDa) and GmrD (27 kDa) were purified and found to be inactive
      separately, but together degraded several different glc-HMC modified DNAs (T4, T2
      and T6). The GMR enzyme is able to degrade both alpha-glucosy-HMC T4 DNA and beta
      glucosyl-HMC T4 DNA, whereas no activity was observed against non-modified DNAs
      including unmodified T4 cytosine (C) DNA or non-glucosylated T4 HMC DNA. Enzyme
      activity requires NTP, favors UTP, is stimulated by calcium, and initially
      produces 4 kb DNA fragments that are further degraded to low molecular mass
      products. The enzyme is inhibited by the T4 phage internal protein I* (IPI*) to
      which it was found to bind. Overall activities of the purified GmrSD enzyme are
      in good agreement with the properties of the cloned gmr genes in vivo and suggest
      a restriction enzyme specific for sugar modified HMC DNAs. IPI* thus represents a
      third generation bacteriophage defense against restriction nucleases of the Gmr
      type.

PMID- 17188298
TI  - Limping of homodimeric kinesin motors.
AB  - Conventional kinesin, a homodimeric motor protein that transports cargo in
      various cells, walks limpingly along microtubule. Here, based on our previously
      proposed partially coordinated hand-over-hand model, we present a new mechanism
      for the limping behaviors of both wild-type and mutant kinesin homodimers. The
      limping is caused by different vertical forces acting on the heads in two
      successive steps during the processive movement of the dimer. From the model,
      various theoretical results, such as the dependences of the mean dwell time and
      dwell time ratio on the coiled-coil length and on the external load as well as
      the effect of vertical force on velocity, are in good agreement with previous
      experimental results. We predict that a high degree of limping will correlate
      strongly with a high sensitivity of ATP turnover rate to upwards force.

PMID- 17188299
TI  - Cryptochrome 3 from Arabidopsis thaliana: structural and functional analysis of
      its complex with a folate light antenna.
AB  - Cryptochromes are almost ubiquitous blue-light receptors and act in several
      species as central components of the circadian clock. Despite being evolutionary
      and structurally related with DNA photolyases, a class of light-driven DNA-repair
      enzymes, and having similar cofactor compositions, cryptochromes lack DNA-repair
      activity. Cryptochrome 3 from the plant Arabidopsis thaliana belongs to the DASH
      type subfamily. Its crystal structure determined at 1.9 Angstroms resolution
      shows cryptochrome 3 in a dimeric state with the antenna cofactor 5,10
      methenyltetrahydrofolate (MTHF) bound in a distance of 15.2 Angstroms to the U
      shaped FAD chromophore. Spectroscopic studies on a mutant where a residue crucial
      for MTHF-binding, E149, was replaced by site-directed mutagenesis demonstrate
      that MTHF acts in cryptochrome 3 as a functional antenna for the photoreduction
      of FAD.

PMID- 17188300
TI  - The first crystal structure of L-threonine dehydrogenase.
AB  - L-threonine dehydrogenase (TDH) is an enzyme that catalyzes the oxidation of L
      threonine to 2-amino-3-ketobutyrate. We solved the first crystal structure of a
      medium chain L-threonine dehydrogenase from a hyperthermophilic archaeon,
      Pyrococcus horikoshii (PhTDH), by the single wavelength anomalous diffraction
      method using a selenomethionine-substituted enzyme. This recombinant PhTDH is a
      homo-tetramer in solution. Three monomers of PhTDHs were located in the
      crystallographic asymmetric unit, however, the crystal structure exhibits a homo
      tetramer structure with crystallographic and non-crystallographic 222 symmetry in
      the cell. Despite the low level of sequence identity to a medium-chain NAD(H)
      dependent alcohol dehydrogenase (ADH) and the different substrate specificity,
      the overall folds of the PhTDH monomer and tetramer are similar to those of the
      other ADH. Each subunit is composed of two domains: a nicotinamide cofactor
      (NAD(H))-binding domain and a catalytic domain. The NAD(H)-binding domain
      contains the alpha/beta Rossmann fold motif, characteristic of the NAD(H)-binding
      protein. One molecule of PhTDH contains one zinc ion playing a structural role.
      This metal ion exhibits coordination with four cysteine ligands and some of the
      ligands are conserved throughout the structural zinc-containing ADHs and TDHs.
      However, the catalytic zinc ion that is coordinated at the bottom of the cleft in
      the case of ADH was not observed in the crystal of PhTDH. There is a significant
      difference in the orientation of the catalytic domain relative to the coenzyme
      binding domain that results in a larger interdomain cleft.

PMID- 17188301
TI  - Predictors of quality of life among patients with multiple sclerosis: an Italian
      cross-sectional study.
AB  - The Functional Assessment of Multiple Sclerosis (FAMS) quality of life (QoL)
      instrument is a disease-specific, self-report questionnaire that was developed
      originally for US English-speaking patients. Here, the psychometric properties of
      the FAMS QoL questionnaire for Italian-speaking patients with multiple sclerosis
      (MS) are evaluated and compared with the results from the original FAMS
      validation survey (n=377). Eighteen Italian centers and 344 patients with MS
      participated in the study. The overall reliability (as expressed by Cronbach's
      alpha value) of the FAMS score, and its subscale scores, was always over the
      threshold of 0.8. Patients with benign MS showed a better overall QoL compared
      with patients with relapsing-remitting MS (RRMS; p=0.017), whereas patients with
      RRMS had a better QoL than patients with primary progressive MS (PPMS). No
      difference in QoL was found between patients with PPMS and those with secondary
      progressive MS. The Italian FAMS questionnaire is a valid measure to assess the
      QoL concerns of patients with MS. FAMS is also easy to administer and is well
      accepted by patients.

PMID- 17188302
TI  - Developing a neurology training program in Honduras: a joint project of
      neurologists in Honduras and the World Federation of Neurology.
AB  - One of the major barriers to the provision of quality care for patients with
      neurological disorders in developing countries is a low ratio of neurologists per
      inhabitants, the World Health Organization recommends one neurologist per
      100,000. In 1998 Honduras had one neurologist per 325,000 inhabitants and all the
      neurologists were trained outside the country. The Education Committee of the
      World Federation of Neurology (WFN), in collaboration with the Postgraduate
      Direction of the National Autonomous University of Honduras, the Honduran
      Neurological Association, and the Honduran Secretary of Health helped establish
      the country's first Neurology Training Program in 1998. This program was
      established using a problem- and epidemiological-oriented methodology with
      oversight by an external WFN review board. By 2006 the program has resulted in a
      31% increase in the national neurologist ratio per inhabitant, significantly
      improved the quality of patient care and promoted research in the neurosciences.
      The Honduras Neurology Training Program has provided a valuable model for other
      developing countries with similar needs for neurological care. Based on this
      Honduras experience, members of the Education Committee of the WFN have
      established guidelines for neurology training programs in developing countries.

PMID- 17188303
TI  - Asymptotic states and topological structure of an activation-deactivation
      chemical network.
AB  - The influence of the topology on the asymptotic states of a network of
      interacting chemical species has been studied by simulating its time evolution.
      Random and scale-free networks have been designed to support relevant features of
      activation-deactivation reactions networks (mapping signal transduction networks)
      and the system of ordinary differential equations associated to the dynamics has
      been numerically solved. We analysed stationary states of the dynamics as a
      function of the network's connectivity and of the distribution of the chemical
      species on the network; we found important differences between the two topologies
      in the regime of low connectivity. In particular, only for low connected scale
      free networks it is possible to find zero activity patterns as stationary states
      of the dynamics which work as signal off-states. Asymptotic features of random
      and scale-free networks become similar as the connectivity increases.

PMID- 17188304
TI  - The evolution of function-valued traits for conditional cooperation.
AB  - In this paper we study the evolution of function-valued traits for cooperation in
      environments that display varying degrees of population viscosity. Traits measure
      an individual's intrinsic propensity to cooperate in a standard bilateral
      Prisoner's dilemma and can be increasing, decreasing or constant functions of the
      probability to interact with individuals of ones own genotype. We first analyse
      adaptation to homogenous environments (with constant degree of viscosity).
      Comparing environments characterized by different degrees of viscosity, we find
      that the relation between viscosity and the equilibrium type distribution is not
      monotone. In fact, it is possible that in fluid populations (no viscosity) there
      is more cooperation in equilibrium than in populations with intermediate degrees
      of viscosity. In a second step we analyse heterogenous environments (with varying
      degrees of viscosity). We find that under very weak assumptions on the
      distribution of the viscosity parameter strictly increasing functions are always
      selected and under some parameter constellations they are uniquely so.

PMID- 17188305
TI  - A quantitative kinetic model for ATP-induced intracellular Ca2+ oscillations.
AB  - A quantitative kinetic model is proposed to simulate the ATP-induced
      intracellular Ca(2+) oscillations. The quantitative effect of ATP concentration
      upon the oscillations was successfully simulated. Our simulation results support
      previous experimental explanations that the Ca(2+) oscillations are mainly due to
      interaction of Ca(2+) release from the endoplasmic reticulum (ER) and the ATP
      dependent Ca(2+) pump back into the ER, and the oscillations are prolonged by
      extracellular Ca(2+) entry that maintains the constant Ca(2+) supplies to its
      intracellular stores. The model is also able to simulate the sudden disappearance
      phenomenon of the Ca(2+) oscillations observed in some cell types by taking into
      account of the biphasic characteristic of the Ca(2+) release from the endoplasmic
      reticulum (ER). Moreover, the model simulation results for the Ca(2+)
      oscillations characteristics such as duration, peak [Ca(2+)](cyt), and average
      interval, etc., lead to prediction of some possible factors responsible for the
      variations of Ca(2+) oscillations in different types of cells.

PMID- 17188306
TI  - Multi-scale modeling of a wound-healing cell migration assay.
AB  - A continuum model and a discrete model are developed to capture the population
      scale and cell-scale behavior in a wound-healing cell migration assay created
      from a scrape wound in a confluent cell monolayer. During wound closure, the cell
      population forms a sustained traveling wave, with close contact between cells
      behind the wavefront. Cells exhibit contact inhibition of migration and contact
      limited proliferation. The continuum model includes the two dominant mechanisms
      and characteristics of cell migration and proliferation, using a cell diffusivity
      function that decreases with cell density and a logistic proliferative growth
      term. The discrete model arises naturally from the continuum model. Individual
      cells are simulated as continuous-time random walkers with nearest-neighbor
      transitions, together with a birth/death process. The migration and proliferation
      parameters are determined by analysing individual mice 3T3 fibroblast cell
      trajectories obtained during the development of a confluent cell monolayer and in
      a wound healing assay. The population-scale model successfully predicts the shape
      and speed of the traveling wave, while the discrete model is also successful in
      capturing the contact inhibition of migration effects.

PMID- 17188307
TI  - Gastric protection by alpha-melanocyte-stimulating hormone against ethanol in
      rats: involvement of somatostatin.
AB  - The proopiomelanocortin-derived tridecapeptide alpha-melanocyte-stimulating
      hormone (alpha-MSH) is a neuropeptide that exerts broad anti-inflammatory actions
      in mammals. This study aimed to investigate the effect of alpha-MSH on ethanol
      induced gastric ulcer in rats and to evaluate the involvement of endogenous
      somatostatin in the actions of the peptide. The rats received 1 mL 75% ethanol or
      saline orally. alpha-MSH was given (25 micro g/rat; i.p.) alone or following the
      somatostatin antagonist cyclo-(7-aminoheptanoyl-PH-E-d-Trp-Lys-THR) (10
      microM/kg; i.p.) administration. Gastric lesions were scored macroscopically and
      microscopically following decapitation at 30 min after ethanol challenge. Gastric
      malondialdehyde (MDA) level, myeloperoxidase (MPO) activity and mast cell counts
      were assessed. Ethanol-induced gastric hemorrhagic lesions were characterized by
      increased gastric MDA level, MPO activity and mast cell counts. alpha-MSH
      treatment decreased the extent of tissue injury and reversed tissue MDA level,
      MPO activity and mast cell counts. The effect of the peptide on the severity of
      gastric lesions, MDA level and MPO activity was reversed by the somatostatin
      antagonist. In conclusion, alpha-MSH is beneficial in a rat model of gastric
      ulcer via mechanisms which partly involve the endogenous somatostatin.

PMID- 17188308
TI  - Trace metal characterisation of marine sediment reference materials MESS-3 and
      PACS-2 in dilute HCl extracts.

PMID- 17188309
TI  - Biological control does not imply paradox.
AB  - Is the classical predator-prey theory inherently pathological? Defenders of the
      theory are losing ground in the debate. We will demonstrate that detractors' main
      argument is based on a faulty model, and that the conceptual and predictive bases
      of the theory are fundamentally sound.

PMID- 17188310
TI  - Skin microcirculatory effect of exogenous calcitonin gene-related peptide (CGRP)
      evaluated by laser Doppler flowmetry coupled with iontophoresis in healthy
      subjects.
AB  - The aim of our study was to evaluate the feasibility of laser Doppler flowmetry
      (LDF) coupled with iontophoresis in exploring the skin vasodilator activity of
      exogenous calcitonin gene-related peptide (CGRP) in healthy subjects and to
      investigate the mechanisms involved in the skin vasodilator activity of this
      peptide. Forearm skin blood perfusion was measured in conventional perfusion unit
      (PU; 1 PU=10 mV), using a LDF apparatus (Periflux PF4001, Perimed, Sweden),
      before and following exogenous CGRP dissolved in distilled water (0.02%) or pure
      saline iontophoresis. Different iontophoresis protocols were used in a
      preliminary dose finding study in six subjects. Two pulses (0.1 mA for 30 s each)
      of anodal CGRP or saline iontophoresis were used in the definitive study in 20
      subjects. Power spectral density (PSD) of skin blood flowmotion frequency
      intervals (FI), related to endothelial (0.009-0.02 Hz), sympathetic (0.02-0.06
      Hz), myogenic (0.06-0.2 Hz), respiratory (0.2-0.6 Hz) and heart (0.6-1.6 Hz)
      activities, was also measured in PU(2)/Hz, by means of spectral analysis of the
      skin LDF signal registered before and following iontophoresis of CGRP or saline
      in the definitive study. A significantly higher per cent increase in skin
      perfusion compared to baseline was observed following CGRP than saline
      iontophoresis (548+/-369% vs. 326+/-192%, p<0.05), with higher hyperaemic
      response to pure saline than CGRP iontophoresis in only five subjects. A
      significant increase (p<0.05) in PSD mean value of the five FI considered, was
      also observed following CGRP iontophoresis, while saline iontophoresis elicited a
      significant increase (p<0.05) only in PSD of the FI related to endothelial,
      respiratory and heart activity. These findings demonstrated that LDF coupled with
      iontophoresis is a feasible method in evaluating the vasodilator effect of
      exogenous CGRP in human skin and suggest that this peptide directly or indirectly
      induces a smooth muscle vascular cells and sympathetic fibres stimulation.

PMID- 17188311
TI  - Cognitive sequence learning in Parkinson's disease and amnestic mild cognitive
      impairment: Dissociation between sequential and non-sequential learning of
      associations.
AB  - Evidence suggests that dopaminergic mechanisms in the basal ganglia (BG) are
      important in the learning of sequential associations. To test the specificity of
      this hypothesis, we assessed never-medicated patients with Parkinson's disease
      (PD) and amnestic mild cognitive impairment (aMCI) using a chaining task. In the
      training phase of the chaining task, each link in a sequence of stimuli leading
      to reward is trained step-by-step using feedback after each decision, until the
      complete sequence is learned. In the probe phase of the chaining task, the
      context of stimulus-response associations must be used (the position of the
      associations in the sequence). Results revealed that patients with PD showed
      impaired learning during the training phase of the chaining task, but their
      performance was spared in the probe phase. In contrast, patients with aMCI with
      prominent medial temporal lobe (MTL) dysfunctions showed intact learning during
      the training phase of the chaining task, but their performance was impaired in
      the probe phase of the chaining task. These results indicate that when
      dopaminergic mechanisms in the BG are dysfunctional, series of stimulus-response
      associations are less efficiently acquired, but their sequential manner is
      maintained. In contrast, MTL dysfunctions may result in a non-sequential learning
      of associations, which may indicate a loss of contextual information.

PMID- 17188312
TI  - Wheat cells accumulate a syringyl-rich lignin during the hypersensitive
      resistance response.
AB  - The stem rust fungus Puccinia graminis f.sp. tritici is an obligately biotrophic
      pathogen attacking wheat (Triticum aestivum). In compatible host/pathogen
      interactions, the fungus participates in the host's metabolism by establishing
      functional haustoria in the susceptible plant cells. In highly resistant wheat
      cultivars, fungal attack is stopped by a hypersensitive response of penetrated
      host cells. This mechanism of programmed cell death of single plant cells is
      accompanied by the intracellular accumulation of material with UV-fluorescence
      typical of phenolic compounds. A similar reaction can be induced in healthy wheat
      leaves by the application of a rust-derived elicitor. We analysed the biochemical
      composition of this defense-induced phenolic material. Contents of total soluble
      and cell wall esterified and etherified phenolic acids were determined in rust
      inoculated and elicitor-treated leaves of the fully susceptible wheat cultivar
      Prelude and its highly resistant, near-isogenic line Prelude-Sr5. While no
      resistance-related changes occured in any of these fractions, the lignin content
      as determined by the thioglycolic acid and the acetyl bromide methods increased
      after elicitor treatment. Nitrobenzene oxidation revealed that the entire
      increase can be explained by an increase in syringyl units only. These
      biochemical data were confirmed by fluorescence emission spectra analyses which
      indicated a defense-induced enrichment of syringyl lignin for cell wall samples
      both from elicitor-treated wheat leaves and single host cells undergoing a
      hypersensitive response upon fungal penetration.

PMID- 17188314
TI  - When is public health really going to influence service quality?

PMID- 17188313
TI  - ACAT inhibition of alkamides identified in the fruits of Piper nigrum.
AB  - In this study, via a bioactivity-guided fractionation of MeOH extracts of the
      fruits of Piper nigrum, alkamide (5) and five previously-identified alkamides
      were isolated. Their structures were elucidated via spectroscopic analysis ((1)H,
      (13)C NMR and ESI-MS), as follows: retrofractamide A (1), pipercide (2),
      piperchabamide D (3), pellitorin (4), dehydroretrofractamide C (5) and
      dehydropipernonaline (6). The IC(50) values determined for the compounds were
      24.5 (1), 3.7 (2), 13.5 (3), 40.5 (4), 60 (5) and 90 microM (6), according to the
      results of an ACAT enzyme assay system using rat liver microsomes. These
      compounds all inhibited cholesterol esterification in HepG2 cells.

PMID- 17188315
TI  - Hematology and serum biochemistry of Holstein dairy calves: age related changes
      and comparison with blood composition in adults.
AB  - Specific reference intervals are needed for each animal species for appropriate
      interpretation of hematological and serum biochemical results. The aim of the
      present study was to investigate the blood composition of growing calves in order
      to evaluate the need for defining reference values for different age groups.
      Thirty two Holstein calves (18 male and 14 female) were blood sampled. A blood
      sample was taken within 24-48 h following birth and at 14, 28, 42, 56, 70 and 84
      days of age. CBC determination and the measurements of some blood serum
      metabolites, enzymes, electrolytes and minerals were performed. There were
      significant age related changes for most hematological and biochemical parameters
      (p < 0.05) except for the numbers of band neutrophils and monocytes and the
      amounts of sodium, potassium, chloride and BUN. The results of the present study
      showed that for some hematological and biochemical parameters such as hemoglobin,
      MCV, MCH, MCHC, inorganic phosphorus, serum total protein, globulin, AST and ALP
      at the first three months of life and also, neutrophil numbers and glucose levels
      at the 24-48 h of life, the age specific reference values must be considered for
      precise interpretation of laboratory results.

PMID- 17188316
TI  - Neuronal oxidative injury and dendritic damage induced by carbofuran: protection
      by memantine.
AB  - Carbamate insecticides mediate their neurotoxicity by acetylcholinesterase (AChE)
      inactivation. Male Sprague-Dawley rats acutely intoxicated with the carbamate
      insecticide carbofuran (1.5 mg/kg, sc) developed hypercholinergic signs within 5
      7 min of exposure, with maximal severity characterized by seizures within 30-60
      min, lasting for about 2 h. At the time of peak severity, compared with controls,
      AChE was maximally inhibited (by 82-90%), radical oxygen species (ROS) markers
      (F(2)-isoprostanes, F(2)-IsoPs; and F(4)-neuroprostanes, F(4)-NeuroPs) were
      elevated 2- to 3-fold, and the radical nitrogen species (RNS) marker citrulline
      was elevated 4- to 8-fold in discrete brain regions (cortex, amygdala, and
      hippocampus). In addition, levels of high-energy phosphates (HEPs) were
      significantly reduced (ATP, by 43-56%; and phosphocreatine, by 37-48%). Values of
      total adenine nucleotides and total creatine compounds declined markedly (by 41
      56% and 35-45%, respectively), while energy charge potential remained unchanged.
      Quantitative morphometric analysis of pyramidal neurons of the hippocampal CA1
      region revealed significant decreases in dendritic lengths (by 64%) and spine
      density (by 60%). Pretreatment with the N-methyl-D-aspartate (NMDA) receptor
      antagonist memantine (18 mg/kg, sc), in combination with atropine sulfate (16
      mg/kg, sc), significantly attenuated carbofuran-induced changes in AChE activity
      and levels of F(2)-IsoPs and F(4)-NeuroPs, declines in HEPs, as well as the
      alterations in morphology of hippocampal neurons. MEM and ATS pretreatment also
      protected rats from carbofuran-induced hypercholinergic behavioral activity,
      including seizures. These findings support the involvement of ROS and RNS in
      seizure-induced neuronal injury and suggest that memantine by preventing
      carbofuran-induced neuronal hyperactivity blocks pathways associated with
      oxidative damage in neurons.

PMID- 17188317
TI  - Brain regional acetylcholinesterase activity and muscarinic acetylcholine
      receptors in rats after repeated administration of cholinesterase inhibitors and
      its withdrawal.
AB  - Activity of acetylcholinesterase (AChE) and specific binding of
      [(3)H]quinuclidinyl benzilate (QNB), [(3)H]pirenzepine (PZP) and [(3)H]AF-DX 384
      to muscarinic acetylcholine receptor (mAChR) preparations in the striatum,
      hippocampus and cortex of rats were determined 1, 6 and 11 days after the last
      treatment with an organophosphate DDVP, a carbamate propoxur or a muscarinic
      agonist oxotremorine as a reference for 7 and 14 days. AChE activity was markedly
      decreased in the three regions 1 day after the treatment with DDVP for 7 and 14
      days with a gradual recovery 6 to 11 days, and much less decreased 1, 6 and 11
      days after the treatment with propoxur for 7 days but not for 14 days in the
      hippocampus and cortex. The binding of [(3)H]-QNB, PZP and AF-DX 384 in the three
      regions was generally decreased by the treatment with DDVP for 7 and 14 days.
      Such down-regulations were generally restored 6 or 11 days after the treatment
      for 7 but not for 14 days. The down-regulation or up-regulation as measured by
      [(3)H]-QNB, PZP and AF-DX 384 was observed 1, 6 or 11 days after treatment with
      propoxur for 7 days and/or 14 days. Repeated treatment with oxotremorine produced
      similar effects except AChE activity to DDVP. These results suggest that repeated
      inhibition of AChE activity may usually cause down-regulation of mAChRs with some
      exception in the hippocampus when a reversible antiChE propoxur is injected.

PMID- 17188318
TI  - Host-related nucleotide composition and codon usage as driving forces in the
      recent evolution of the Astroviridae.
AB  - The evolutionary history of the Astroviridae comprises the ancient separation
      between avian and mammalian astrovirus lineages followed by diversification among
      mammalian astroviruses. The latter process included several cross-species
      transmissions. We found that the recent, but not the ancient, evolution of
      astroviruses was associated with a switch in nucleotide composition and codon
      usage among non-human mammalian versus human/avian astroviruses. Virus and hosts
      phylogenies based on codon usage agreed with each other and matched the hosts'
      evolutionary emergence order. This recent switch in driving forces acting at the
      synonymous level points to the adaptation of codon usage by viruses to that of
      their hosts after cross-species transmissions. This is the first demonstration of
      nucleotide composition and codon usage being active driving forces during the
      recent evolutionary history of a virus group in the host-parasite system.

PMID- 17188320
TI  - Members of the HCMV US12 family of predicted heptaspanning membrane proteins have
      unique intracellular distributions, including association with the cytoplasmic
      virion assembly complex.
AB  - The human cytomegalovirus (HCMV) US12 gene family is a group of 10 predicted
      seven-transmembrane domain proteins that have some features in common with G
      protein-coupled receptors. Little is known of their patterns of expression,
      localization, or functional interactions. Here, we studied the intracellular
      localization of three US12 family members, US14, US17, and US18, with respect to
      various intracellular markers and the cytoplasmic virion assembly compartment
      (AC). The three proteins have distinct patterns of expression, which include
      associations with the AC. US14 is often distributed in a uniform granular manner
      throughout the cytoplasm, concentrating in the AC in some cells. US17 is
      expressed in a segmented manner, with its N-terminal domain localizing to the
      periphery of what we show here to be the AC and the C-terminal domain localizing
      to nuclei and the cytoplasm [Das, S., Skomorovska-Prokvolit, Y., Wang, F. Z.,
      Pellett, P.E., 2006. Infection-dependent nuclear localization of US17, a member
      of the US12 family of human cytomegalovirus-encoded seven-transmembrane proteins.
      J. Virol. 80, 1191-1203]. Here, we show that the C-terminal domain is present at
      the center of the AC, in close association with markers of early endosomes; the N
      terminal staining corresponds to an area stained by markers for the Golgi and
      trans-Golgi. US18 is distributed throughout the cytoplasm, concentrating in the
      AC at later stages of infection; it is localized more to the periphery of the AC
      than are US14 and US17C, in association with markers of the trans-Golgi. Although
      not detected in virions, their structures and localization in various zones
      within the AC suggest possible roles for these proteins in the process of virion
      maturation and egress.

PMID- 17188319
TI  - Visualization of the herpes simplex virus portal in situ by cryo-electron
      tomography.
AB  - Herpes simplex virus type 1 (HSV-1), the prototypical herpesvirus, has an
      icosahedral nucleocapsid surrounded by a proteinaceous tegument and a lipoprotein
      envelope. As in tailed bacteriophages, the icosahedral symmetry of the capsid is
      broken at one of the 12 vertices, which is occupied by a dodecameric ring of
      portal protein, UL6, instead of a pentamer of the capsid protein, UL19. The
      portal ring serves as a conduit for DNA entering and exiting the capsid. From a
      cryo-EM reconstruction of capsids immuno-gold-labeled with anti-UL6 antibodies,
      we confirmed that UL6 resides at a vertex. To visualize the portal in the context
      of the assembled capsid, we used cryo-electron tomography to determine the three
      dimensional structures of individual A-capsids (empty, mature capsids). The
      similarity in size and overall shape of the portal and a UL19 pentamer--both are
      cylinders of approximately 800 kDa--combined with residual noise in the
      tomograms, prevented us from identifying the portal vertices directly; however,
      this was accomplished by a computational classification procedure. Averaging the
      portal-containing subtomograms produced a structure that tallies with the
      isolated portal, as previously reconstructed by cryo-EM. The portal is mounted on
      the outer surface of the capsid floor layer, with its narrow end pointing
      outwards. This disposition differs from that of known phage portals in that the
      bulk of its mass lies outside, not inside, the floor. This distinction may be
      indicative of divergence at the level of portal-related functions other than its
      role as a DNA channel.

PMID- 17188322
TI  - Sorption of cesium, cobalt and europium on low-rank coal and chitosan.
AB  - Potential low-cost sorbents of metals based on combined action of coal and
      chitosan have been investigated. Sorption of Cs, Co and Eu on oxidized coals in
      mixture with chitosan was studied as function of pH ( approximately 3-6) in batch
      experiments using radiotracer method. An improved sorption efficiency of the coal
      sorbents at neutral pH was obtained in mixture with chitosan, namely for
      oxihumolite at sorption of Eu and Co. Chitosan prevented deterioration of the
      sorption ability of coal with pH increase probably via retaining the soluble
      complexes with humic substances leached from coal by formation of an insoluble
      complex. The effect of chitosan addition was negligible or reverse in case of
      lignite upon acidification, where the interaction takes place preferentially on
      the coal surface and may restrict availability of the binding sites for metal
      ions.

PMID- 17188321
TI  - Sensitivity and configuration-specificity of orientation-defined texture
      processing in infants and adults.
AB  - Here we use textures made up of widely spaced Gabor patches to compare infant and
      adult sensitivity to the global organization of the elements comprising the
      textures. Visual Evoked Potentials (VEPs) were recorded to alterations between
      random images and images containing varying proportions of patches that were of
      the same orientation. The patches were placed on rectangular, hexagonal or random
      lattices. Texture-specific responses were robust in adults and their VEP
      threshold was reached when 1-17% of the patches had the same orientation in the
      structured image. Infant thresholds were approximately 20-60%. While infants are
      capable of detecting the global structure of our textures, their sensitivity is
      low. In adults we found, unexpectedly, that sensitivity and response gain were
      higher for horizontal compared to vertical global orientations. Infant
      sensitivity was the same for the two orientations. Comparable orientation
      anisotropies have not been previously reported for gratings, suggesting that the
      Gabor-defined textures are tapping different mechanisms. There were small, but
      measurable effects of the lattice type in adults, with the rectangular lattice
      producing the largest responses.

PMID- 17188323
TI  - Remediation of heavy metals contaminated soils by ball milling.
AB  - In the present work, the use of ball milling reactors for the remediation of lead
      contaminated soils was investigated. Lead immobilization was achieved without the
      use of additional reactants but only through the exploitation of weak
      transformations induced on the treated soil by mechanical loads taking place
      during collisions among milling media. The degree of metal immobilization was
      evaluated by analyzing the leachable fraction of Pb(II) obtained through the
      "synthetic precipitation leaching procedure". The reduction of leachable Pb(II)
      from certain synthetic soils, i.e., bentonitic, sandy and kaolinitc ones, was
      obtained under specific milling regimes. For example, for the case of bentonitic
      soils characterized by a Pb(II) concentration in the solid phase equal to 954.4
      mg kg(-1), leachable Pb(II) was reduced, after 7 h of mechanical treatment, from
      1.3 mg l(-1) to a concentration lower than the USEPA regulatory threshold (i.e.,
      0.015 mg l(-1) for drinkable water). Similar results were obtained for sandy and
      kaolinitic soils. X-ray diffraction, scanning electron microscopy, electron
      dispersive spectroscopy and granulometric analyses revealed no significant
      alterations of the intrinsic character of sandy and bentonitic soils after
      milling except for a relatively small increase of particles size and a partial
      amorphization of the treated soil. On the other hand, the mechanical treatment
      caused the total amorphization of kaolinitic soil. The increase of immobilization
      efficiency can be probably ascribed to specific phenomena induced by mechanical
      treatment such as entrapment of Pb(II) into aggregates due to aggregation, solid
      diffusion of Pb(II) into crystalline reticulum of soil particles as well as the
      formation of new fresh surfaces (through particle breakage) onto which Pb(II) may
      be irreversibly adsorbed.

PMID- 17188324
TI  - Volatile organic sulfur compounds in a stratified lake.
AB  - Three volatile organic sulfur compounds (VOSCs), dimethyl sulfide (DMS), carbon
      disulfide (CS(2)), and dimethyl disulfide (DMDS), were detected in the stratified
      water column of a lake (Linsley Pond) in Connecticut. The compounds DMS and DMDS
      appeared in both the oxic and the anoxic portions of the water column, CS(2) was
      primarily found in anoxic hypolimnion. Algal metabolism and/or bacterial
      degradation of sulfur-containing amino acids or other organic materials are
      potential sources of VOSCs in the oxic lake water. Reactions of hydrogen sulfide
      with organic compounds and microbial degradation of organic matter may be
      responsible for the production of VOSCs in the anoxic lake water. The vertical
      distribution patterns of these three VOSCs varied from month to month in the
      summer, but the daily profiles obtained in one 5-day period in the summer
      displayed consistency. No clear diurnal pattern for any of the three VOSCs was
      observed. Based on observation that these VOSCs were not present in surface and
      near surface waters of Linsley Pond, freshwater inputs of reduced sulfur
      compounds to the atmosphere may be insignificant.

PMID- 17188325
TI  - Decomposition pathways and reaction intermediate formation of the purified,
      hydrolyzed azo reactive dye C.I. Reactive Red 120 during ozonation.
AB  - In this study, an aqueous solution of purified, hydrolyzed C.I. Reactive Red 120
      (RR 120, Color Index), was selected as a model to investigate the degradation
      pathways and to obtain additional information on the reaction intermediate
      formation. The dye was purified to avoid the influence of the impurities on the
      ozonation process and on the formation of oxidation by-products. To simulate the
      dye-bath effluents from dyeing processes with azo reactive dyes, a hydrolyzed
      form of the dye was chosen as a representative compound. High performance liquid
      chromatography/mass spectrometry and its tandem mass spectrometry was chosen to
      identify the decomposition pathways and reaction intermediate formation during
      the ozonation process. In addition total organic carbon and high performance ion
      chromatography analysis were employed to obtain further information on the
      reaction processes during ozonation. Purified, hydrolyzed RR 120 was decomposed
      under the direct nucleophilic attack by ozone resulting in oxidation and cleavage
      of azo group and aromatic ring, while the triazine group still remained in the
      solution even after prolonged oxidation time (120 min) due to its high resistance
      to ozonation. Phenol, 1,2-dihydroxysulfobezene, 1-hydroxysulfonbezene were
      detected as the degradation intermediates, which were further oxidized by O(3)
      and *OH to other open-ring products and then eventually led to simple oxalic and
      formic acid identified by HPIC.

PMID- 17188327
TI  - Advantages of combined touch screen technology and text hyperlink for the
      pathology grossing manual: a simple approach to access instructive information in
      biohazardous environments.
AB  - Gross examination, encompassing description, dissection, and sampling, is a
      complex task and an essential component of surgical pathology. Because of the
      complexity of the task, standardized protocols to guide the gross examination
      often become a bulky manual that is difficult to use. This problem is further
      compounded by the high specimen volume and biohazardous nature of the task. As a
      result, such a manual is often underused, leading to errors that are potentially
      harmful and time consuming to correct-a common chronic problem affecting many
      pathology laboratories. To combat this problem, we have developed a simple method
      that incorporates complex text and graphic information of a typical procedure
      manual and yet allows easy access to any intended instructive information in the
      manual. The method uses the Object-Linking-and-Embedding function of Microsoft
      Word (Microsoft, Redmond, WA) to establish hyperlinks among different contents,
      and then it uses the touch screen technology to facilitate navigation through the
      manual on a computer screen installed at the cutting bench with no need for a
      physical keyboard or a mouse. It takes less than 4 seconds to reach any intended
      information in the manual by 3 to 4 touches on the screen. A 3-year follow-up
      study shows that this method has increased use of the manual and has improved the
      quality of gross examination. The method is simple and can be easily tailored to
      different formats of instructive information, allowing flexible organization,
      easy access, and quick navigation. Increased compliance to instructive
      information reduces errors at the grossing bench and improves work efficiency.

PMID- 17188326
TI  - Cellular alterations in different organs of European sea bass Dicentrarchus
      labrax (L.) exposed to cadmium.
AB  - Specimens of farmed European sea bass (Dicentrarchus labrax L., 1758) were
      exposed to different cadmium (Cd) concentrations (4.47, 5.63, 7.08 and 8.91 mg l(
      1)) for 24 and 48 h. The effects of Cd on numbers of some cell types and
      structures (i.e., chloride cells, CCs; macrophage aggregates, MAs; rodlet cells,
      RCs) and on structure and ultrastructure of the main organs (gill, liver,
      intestine, kidney) were studied with routine process for light and transmission
      electron microscopy. Following cadmium exposure, the numbers of branchial CCs as
      well as intestinal and renal RCs increased significantly within 24h. Increase in
      metal concentration did not affect the magnitude of the numerical increment of
      the aforementioned cells. Moreover, in treated fish (24 and 48 h) the numbers of
      MAs in both head kidney and spleen were significantly higher than in control
      conspecifics, whilst the global area of MAs was less influenced by the acute
      treatment. In exposed sea bass, all the examined organs exhibited cellular
      modifications which appeared time- and dose-dependent. The gills showed
      telangectasia, lamellar fusion, oedema, epithelial lifting and leukocyte
      infiltration. In the liver, kidney and intestine acute cell swelling and
      vacuolization were common. Ultrastructurally the alterations observed frequently
      in hepatocytes, tubular epithelial cells and enterocytes included presence of
      numerous myelinoid bodies, damaged mitochondria, dilatation of endoplasmic
      reticulum, high number of lysosomes and autophagolysosomes. In intestinal and
      kidney tubular epithelia of treated fish, rodlet cells displayed some anomalies
      like dilatation of nuclear envelope, cytoplasmic vacuolization, presence of
      myelinoid bodies, rodlets degeneration and extensive discharge activity.

PMID- 17188328
TI  - Case study of the morphologic variation of circulating tumor cells.
AB  - We report a detailed cytomorphologic evaluation of the circulating component of
      widely metastatic breast carcinoma. A previously healthy 38-year-old woman was
      diagnosed with breast cancer. Wide local excision revealed a 1.7-cm infiltrating
      ductal adenocarcinoma, BSR score 7/9 with angiolymphatic invasion, and 4/20 lymph
      nodes positive for carcinoma. Five years later, a bone marrow biopsy revealed
      involvement of bone marrow by metastatic breast carcinoma, and shortly
      thereafter, metastases were identified in the liver and lung hilum. She enrolled
      in a clinical investigation for the detection of circulating tumor cells (CTCs)
      in breast carcinoma. A total of 659 CTCs were identified in a 10-mL blood sample
      using an immunofluorescent protocol targeting cytokeratins and detected using
      fiber-optic array scanning technology. The detected CTCs were subsequently
      stained with a Wright-Giemsa stain, and representative cells were evaluated in
      detail by light microscopy for morphologic evaluation. We find that the patient's
      CTCs exhibit a high degree of pleomorphism including CTCs with high and low
      nuclear-to-cytoplasmic ratios along with CTCs exhibiting early and late apoptotic
      changes. In addition, in comparison with her tumor cells in other sites, the full
      morphologic spectrum of cancer cells present in primary and metastatic tumor is
      also present in peripheral blood circulation.

PMID- 17188329
TI  - Lower expression levels of the transforming growth factor beta receptor type II
      protein are associated with a less aggressive tumor phenotype and improved
      survival among patients with clear cell renal cell carcinoma.
AB  - Loss of expression of the transforming growth factor beta type II receptor
      (TbetaRII) has been implicated as an important event in renal carcinogenesis;
      however, its role as a potential prognostic factor remains poorly understood.
      Using archived tumor samples and long-term follow-up on a cohort of 280 clear
      cell renal cell carcinoma (ccRCC) patients treated with surgery from 1980 to
      1998, we evaluated the association of TbetaRII expression and cancer-specific
      survival in both a univariate and multivariate setting. Low tumor expression of
      TbetaRII is associated with a less aggressive tumor phenotype at time of surgery.
      Moreover, those patients with lower levels of TbetaRII expression experience
      better cancer-specific survival than patients with higher levels of TbetaRII
      expression (log rank P = .034). Based on a Cox proportional hazard model
      adjusting for age, patients with tumors showing low (hazard ratio, 0.49; 95%
      confidence interval, 0.27-0.88) and moderate (hazard ratio, 0.7; 95% confidence
      interval, 0.40-1.23) TbetaRII expression are at decreased risk of RCC death
      compared with patients with tumors having high levels of TbetaRII expression.
      Adjustment for well-known pathologic predictors of RCC outcome attenuates the
      association of TbetaRII expression and ccRCC survival. Of interest, the
      association with TbetaRII expression appears more pronounced among those patients
      with tumors showing less aggressive phenotypes. Data from this investigation are
      the first to suggest that loss of TbetaRII expression is associated with improved
      ccRCC patient survival, especially among those patients with less aggressive
      disease profiles at time of surgery.

PMID- 17188331
TI  - Patterns of recurrent hepatitis C after liver transplantation in a recent cohort
      of patients.
AB  - Clinicopathologic trends of recurrent hepatitis C after liver transplantation
      (LT) in hepatitis C (HCV) patients seem to have changed in recent years. Our aims
      were to define the current post-LT patterns of HCV recurrence and identify
      features of diagnostic and/or prognostic significance. Detailed analysis was
      performed on 92 HCV patients who underwent LT from June 1999 to December 2003 and
      survived early post-LT period. The study patients were grouped, as follows: no
      histologic recurrence (n = 31), "typical" recurrent HCV (n = 52), and post-LT
      autoimmune-like hepatitis ("AIH-like") (n = 9). The typical and AIH-like groups
      had mostly common features with post-LT progressive fibrosis (stage > or =2) more
      frequent in the latter. Based on post-LT progressive fibrosis (stage > or =2),
      the 2 post-LT hepatitis categories were regrouped as progressive (n = 24) and
      nonprogressive (n = 37). High viral counts, HCV genotype 1, and native liver
      inflammation grade 2 or higher with plasmacytic periseptitis were more frequent
      in progressive cases than nonprogressive or nonrecurrent cases. Sex mismatch of
      male recipient and female donor was more common in nonrecurrent group. Overall,
      death rate was comparable in all groups; however, post-LT HCV-related deaths were
      more common in progressive cases. In conclusion (1) two thirds (66.2%) of HCV
      patients developed histologic hepatitis after LT with either typical or AIH-like
      features; (2) progressive fibrosis was seen in 39.3% of patients with post-LT
      hepatitis and 26% of the entire study group and was more frequent in AIH-like
      cases; (3) inflammation grade 2 or higher with plasmacytic periseptitis in native
      livers may be a predictor of post-LT progressive fibrosis; and (4) male
      recipient/female donor combination was more common in nonrecurrent cases.

PMID- 17188330
TI  - Diagnosis of chronic endometritis in biopsies with stromal breakdown.
AB  - Plasma cells are the hallmark of chronic endometritis but are not specific for
      upper tract infection. Plasma cells have also been noted in hormonally mediated
      endometrial disorders in association with gland architectural changes
      ("disordered proliferative" and "anovulatory" patterns), and stromal breakdown.
      We reviewed benign endometrial biopsies diagnosed at Beth Israel Deaconess
      Medical Center over a 2-year period described as disordered/anovulatory patterns
      +/- stromal breakdown. Cases were excluded if tissue was not available; women
      were younger than 50 years where most diagnoses were atrophic or cancer; or
      diagnoses were secretory, menstrual endometrium, or polyps. The remaining 61
      cases were compared to 33 samples of unremarkable proliferative endometrium.
      Plasma cells were quantified on hematoxylin and eosin-stained sections and using
      a histochemical stain methyl green pyronin. The indication for biopsy was an
      abnormal pattern of bleeding in 34 cases, infertility workup in 7, incidental
      part of workup for pain, or other findings in 5. The majority of disordered
      proliferative endometrium had plasma cells (61% grade 1, 17% grade 2) all seen on
      methyl green pyronin staining only. Two thirds of proliferative endometrium with
      breakdown showed plasma cells (19% grade 1, 39% grade 2, 10 % grade 3). Plasma
      cells were rare in inactive endometrium and noted in only 18% of unremarkable
      proliferative endometrium, all grade 1. Plasma cells are commonly present in the
      endometrium of women with dysfunctional uterine bleeding and focal stromal
      breakdown. Given the lack of clinical evidence for infection, the inflammation
      likely represents a physiologic process.

PMID- 17188332
TI  - Increased expression of the Nogo receptor in the hippocampus and its relation to
      the neuropathology in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most prevalent cause of dementia in human beings.
      Its best-known pathologic feature is the presence of senile plaques and
      neurofibrillary tangles in the brain. Nogo-66 receptor (NgR) is believed to
      contribute to the inhibitory activities of axon regeneration after injury. This
      study investigated the expression of NgR in the hippocampus and its relation to
      the pathologic changes of AD using immunohistochemistry and double-labeling
      immunofluorescence methods. The results showed that NgR immunoreactivity was
      present in more than 50% of the pyramidal layer cells of the CA1 to CA4 subfields
      of the hippocampus. No significant difference was observed in the number of NgR
      immunopositive cells in the CA1 to CA4 subfields between patients with AD and
      control subjects, whereas the ratio of NgR immunopositive cells to the total
      number of pyramidal layer cells was revealed to be significantly higher in the
      CA1 and CA2 subfields of the hippocampus of patients with AD than that in the
      same region of the control subjects. Moreover, high numbers of AT-8
      immunopositive cells were found to be double-labeled with NgR in the CA1
      subfields of patients with AD, whereas only few NgR deposits were observed in the
      senile plaques of the hippocampus in these patients. These results suggest that
      NgR may be related to the formation of tangles in AD.

PMID- 17188334
TI  - Metal profiles used as environmental markers of green turtle (Chelonia mydas)
      foraging resources.
AB  - The Baja California Peninsula, Mexico serves an important role for feeding and
      developing sea turtles. High concentrations of metals detected in green turtles
      (Chelonia mydas) from Magdalena Bay prompted an investigation into the sources of
      metals in the region. We compared metal concentrations in sea turtle tissues with
      plant species found in their stomach contents, and with the same species of
      plants collected inside a sea turtle refuge area known as Estero Banderitas.
      Differences in the metal concentrations between marine plant species were
      minimal. Principal components analysis of the percent contribution of individual
      metals to the overall metal signature of each plant or tissue sample generated
      three principal components that explained 80.7% of the total variance in the
      data. The plant samples collected within Estero Banderitas formed a separate
      grouping from the green turtle tissue samples and the plants from the stomach
      contents. The plants in the stomach contents contained greater percent
      contributions of Cd and Zn than the plants collected inside the bay, while Pb and
      Mn contributed more to the metal profiles in the bay samples. The metal profiles
      in the sea turtle tissues more closely resembled the stomach contents than the
      same species of plants collected within Estero Banderitas, and suggest that sea
      turtles collected inside Magdalena Bay use foraging resources outside of the
      Estero Banderitas region. This work supports the suggestion that metal profiles
      can be used as "environmentally acquired markers" to improve our understanding of
      the extent of sea turtle foraging areas.

PMID- 17188335
TI  - Modelling radon progeny concentration variations in thermal spas.
AB  - Radon and its short-lived progenies (218Po, 214Pb, 214Bi and 214Po) are well
      known radioactive indoor pollutants identified as the major radiation burden
      component of the thermal spa users. Monitoring of short-lived progeny
      concentration is of great importance for short-term dose estimations both for
      bathers and working personnel. A prediction model of the short-lived progeny
      concentration variations was developed and applied on published data of the
      thermal spas of Lesvos Island. The physical procedures involved were modeled in a
      set of differential equations describing radon progeny concentration variations
      on the basis of radon measurements. Published daughter data were fitted on model
      predictions adjusting non-measured parameters, e.g. attachment and deposition
      rate constants for attached and unattached progenies. Attachment rate constants
      were estimated between 50 and 200 h-1 while the deposition rate constants between
      0.25 and 5 h-1 for attached progenies and 0.5 and 170 h-1 for the unattached
      ones. In addition, unattached 218Po, 214Pb and 214Bi progenies were found to be
      shifted forward in respect to radon approximately 0.001 h, 0.05 h and 0.40 h
      respectively, while attached 218Po, 214Pb and 214Bi progenies 0.05 h, 0.45 h and
      0.65 h respectively.

PMID- 17188333
TI  - Caspase-2 deficiency enhances aging-related traits in mice.
AB  - Alteration of apoptotic activity has been observed in a number of tissues in
      aging mammals, but it remains unclear whether and/or how apoptosis may affect
      aging. Caspase-2 is a member of the cysteine protease family that plays a
      critical role in apoptosis. To understand the impact of compromised apoptosis
      function on mammalian aging, we conducted a comparative study on caspase-2
      deficient mice and their wild-type littermates with a specific focus on the aging
      related traits at advanced ages. We found that caspase-2 deficiency enhanced a
      number of traits commonly seen in premature aging animals. Loss of caspase-2 was
      associated with shortened maximum lifespan, impaired hair growth, increased bone
      loss, and reduced body fat content. In addition, we found that the livers of
      caspase-2 deficient mice had higher levels of oxidized proteins than those of age
      matched wild-type mice, suggesting that caspase-2 deficiency compromised the
      animal's ability to clear oxidatively damaged cells. Collectively, these results
      suggest that caspase-2 deficiency affects aging in the mice. This study thus
      demonstrates for the first time that disruption of a key apoptotic gene has a
      significant impact on aging.

PMID- 17188336
TI  - Discriminatory classification of natural and anthropogenic waters in two U.K.
      estuaries.
AB  - The ability to distinguish water inputs from both natural and anthropogenic
      sources was investigated in the complex environment of an urban estuary (Tyne)
      and a relatively pristine estuary (Tweed). We used a data set from a total of 11
      estuarine transects, comprising measurements of bulk dissolved organic matter
      (dissolved organic carbon and nitrogen), dissolved nitrogen (total dissolved
      nitrogen, ammonium, nitrate+nitrite and dissolved organic nitrogen), optical
      absorbance measurements (a350, S290-350) and fluorescence excitation emission
      matrix measurements (fluorophores A, H, B and T intensity and A and H emission
      wavelength maxima). In order to investigate trends within the numerous parameters
      measured, multivariate statistics were employed. Principal components analyses
      showed 63.4% of the variability in the total data set can be explained by two
      sets of components and 74.9% of the variability by the spectrophotometric
      measurements alone. In both analyses the first component correlated to the mixing
      of terrestrial and marine waters and the second component was correlated to
      sources of pollution such as domestic sewage. Within the data set, river flow and
      terrestrially derived DOM were significantly correlated, and situations with high
      river input showed an increase in terrestrial signature in the estuary.
      Discriminant analyses were also carried out and indicated that 59.8% (total data
      set) and 53.3% (solely spectrophotometric data) of the samples can be correctly
      classified into their respective groups (water categories) assigned on the basis
      of salinity and sampling location. Overall the results clearly show the potential
      of spectrophotometric techniques to discriminate distinct water categories with
      different DOM characteristics. In particular, measurement of the fluorophore H
      emission maxima, the spectral slope parameter, S290-350, and fluorophores T and B
      intensity enabled discrimination of DOM from riverine, estuarine, marine, and
      sewage affected water categories. The results presented here indicate the ability
      of spectrophotometric data alone to distinguish between marine, anthropogenic and
      terrestrial DOM and distinguish terrestrial DOM from different catchments (Tyne
      vs. Tweed). With current advances in the in-situ deployment of absorbance and
      fluorescence spectroscopy it is anticipated that multivariate statistics will
      gain importance as a cost effective, powerful and diagnostic approach to
      assessing the distributions of water types and their associated DOM
      characteristics and fluxes at the land-ocean interface.

PMID- 17188337
TI  - Evaluating alternative river management options in the tidal Ouse using the
      QUESTS1D model.
AB  - The tidal Ouse forms a significant part of the Humber river system in Eastern
      England, which provides the largest UK fresh water source to the North Sea and a
      valuable habitat for fish. However it suffers from dissolved oxygen (DO) sag in
      summer, exacerbated by the industrial effluent discharged at Selby. A one
      dimensional water quality model, QUESTS1D, as utilized by the Environment Agency
      (EA) has been used to evaluate the effectiveness of management options based on
      exploiting spatial distribution of the assimilative capacity of the river as an
      alternative to implementing more stringent effluent consents. Significant
      improvements in water quality of the tidal Ouse are predicted compared to the
      effects of tightening effluent consents. A system of water quality functions is
      derived in this paper for quicker and more direct predictions of water quality,
      which will be useful in future research when combined with other analyses. Taking
      account the assimilative capacity in policy making, this paper suggests that a
      combined water management framework should be applied to ensure the required
      water quality.

PMID- 17188338
TI  - Persistence of pharmaceuticals and other organic compounds in chlorinated
      drinking water as a function of time.
AB  - Ninety eight pharmaceuticals and other organic compounds (POOCs) that were
      amended to samples of chlorinated drinking-water were extracted and analyzed 1,
      3, 6, 8, and 10 days after amendment to determine whether the total chlorine
      residual reacted with the amended POOCs in drinking water in a time frame similar
      to the residence time of drinking water in a water distribution system. Results
      indicated that if all 98 were present in the finished drinking water from a
      drinking-water treatment plant using free chlorine at 1.2 mg/L as the
      distribution system disinfectant residual, 52 POOCs would be present in the
      drinking water after 10 days at approximately the same concentration as in the
      newly finished drinking water. Concentrations of 16 POOCs would be reduced by 32%
      to 92%, and 22 POOCs would react completely with residual chlorine within 24 h.
      Thus, the presence of free chlorine residual is an effective means for
      transforming some POOCs during distribution.

PMID- 17188339
TI  - Variation and importance of aspirin resistance in patients with known
      cardiovascular disease.
AB  - AIM: To investigate whether aspirin resistance is a persistent condition, and to
      evaluate if aspirin resistance affects one-year clinical outcome. METHODS AND
      RESULTS: Previously we studied 298 patients admitted to hospital with symptoms
      suggestive of an acute myocardial infarction (MI) despite treatment with aspirin,
      and 70 patients (23.5%) were aspirin resistant. In the present study, platelet
      function was reassessed by use of a Platelet Function Analyzer-100 one year
      later. A total of 187 patients were re-examined, and 17 (9.1%) demonstrated
      aspirin resistance. Of these 17 patients, 12 also exhibited aspirin resistance at
      baseline resulting in a 6% (12/187) prevalence of persistent aspirin resistance.
      A total of 34 patients had changed from aspirin resistant at baseline to aspirin
      sensitive at follow-up. We found a significant decrease in the prevalence of
      aspirin resistance from baseline (43%) to follow-up (11%) in patients with MI at
      baseline (p=0.0018). Furthermore, a significant decrease was found for patients
      without MI at baseline (20% to 9%, p=0.0009). During follow-up, 17% (12/70) of
      the patients with aspirin resistance at baseline suffered death, MI or stroke
      compared to 16% (37/227) of aspirin sensitive patients (p=0.868). CONCLUSION: The
      prevalence of aspirin resistance varies with the clinical status of the patients,
      and indeed an acute MI is associated with temporary aspirin resistance. We also
      found that 6% of patients demonstrate persistent aspirin resistance. The presence
      of aspirin resistance did not affect one-year clinical outcome.

PMID- 17188340
TI  - Effects of streptozotocin-induced diabetes on taste buds in rat vallate papillae.
AB  - Some studies have documented taste changes in patients with diabetes mellitus
      (DM). In order to understand the relationships between taste disorders caused by
      DM and the innervation and morphologic changes in the taste buds, we studied the
      vallate papillae and their taste buds in rats with DM. DM was induced in these
      rats with streptozotocin (STZ), which causes the death of beta cells of the
      pancreas. The rats were sacrificed and the vallate papillae were dissected for
      morphometric and quantitative immunohistochemical analyses. The innervations of
      the vallate papillae and taste buds in diabetic and control rats were detected
      using immunohistochemistry employing antibodies directed against protein gene
      product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP). The results
      showed that PGP 9.5- and CGRP-immunoreactive nerve fibers in the trench wall of
      diabetic vallate papillae, as well as taste cells in the taste buds, gradually
      decreased both intragemmally and intergemmally. The morphometry revealed no
      significant difference in papilla size between the control and diabetic groups,
      but there were fewer taste buds per papilla (per animal). The quantification of
      innervation in taste buds of the diabetic rats supported the visual assessment of
      immunohistochemical labeling, that the innervation of taste cells was
      significantly reduced in diabetic animals. These findings suggest that taste
      impairment in diabetic subjects may be caused by neuropathy defects and/or
      morphological changes in the taste buds.

PMID- 17188341
TI  - The relationship between cytokines and HPV-16, HPV-16 E6, E7, and high-risk HPV
      viral load in the uterine cervix.
AB  - OBJECTIVES: To investigate intralesional cytokine levels in precancerous lesions
      of the uterine cervix and their relationship with human papillomavirus (HPV) type
      16, HPV type 16 E6/E7, and high-risk HPV viral load. METHODS: We performed a
      prospective study of 67 patients between May 2005 and December 2005. Hybrid
      Capture II testing was used to identify patients as high-risk HPV DNA-positive or
      -negative. HPV DNA Chip test was performed for HPV genotyping in all cases found
      to be HPV DNA-positive. Real-time PCR was used to quantify HPV-16 E6, E7,
      interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF
      alpha), and interferon gamma (IFN-gamma) transcripts. RESULTS: Among high-risk
      HPV-infected women, intralesional TNF-alpha, IL-6, IL-10, and IFN-gamma levels
      had no significant differences according to histologic grade. In multivariate
      logistic regression analysis, TNF-alpha, IL-6, IL-10, and IFN-gamma were not
      associated with HPV-16. Increased IFN-gamma was significantly associated with HPV
      16 E6- and E7-positive (OR 28.197, 95% CI: 2.658-299.110; OR 19.617, 95% CI:
      2.135-180.253, respectively), whereas TNF-alpha, IL-6, and IL-10 were not
      associated with HPV-16 E6 and E7. In multiple regression analysis, elevated IFN
      gamma was significantly associated with increased HPV viral load (P=0.039),
      whereas TNF-alpha, IL-6, and IL-10 were not significantly associated with HPV
      viral load. CONCLUSIONS: Among HPV-infected women, IFN-gamma is significantly
      associated with HPV-16 E6, E7, and high-risk HPV viral load in the uterine
      cervix. Thus, increased intralesional IFN-gamma may be considered to be a
      prognostic marker for oncogenic potential of high-risk HPV.

PMID- 17188342
TI  - Herpes simplex virus type 2 and Chlamydia trachomatis in adenocarcinoma of the
      uterine cervix.
AB  - INTRODUCTION: Adenocarcinoma of the uterine cervix (AC) occurs in 15-20% of
      primary cervical neoplasias. Although some etiologic factors for squamous cell
      carcinoma are well defined, and its relationship with sexually transmitted
      disease as human papillomavirus (HPV) is established, we still do not know about
      the causative factors of most of AC besides HPV infection. OBJECTIVES: To
      determine the presence of herpes simplex virus type 2 (HSV-2) and Chlamydia
      trachomatis (CT) DNA in AC specimens, and its correlation with HPV infection.
      METHODS: 206 paraffin-embedded cases of AC were selected to DNA extraction. The
      specimens and the DNA were isolated. Samples were first screened for beta-globin
      DNA sequences, and 67 cases were considered adequate to further analysis. In a
      previous analysis, DNA of HPV was identified in 79.4% of specimens included in
      this series (51% HPV 18 and 34% HPV 16). The local ethical committee approved the
      study. RESULTS: All samples were negative for HSV-2 DNA and CT DNA. CONCLUSIONS:
      In our series HSV-2 DNA and CT DNA were not found to be integrated to the genome
      of adenocarcinoma of the uterine cervix and do not seem to be a co-factor for HPV
      on the etiology of this histologic subtype.

PMID- 17188343
TI  - Retroperitoneal lymph node dissection.

PMID- 17188344
TI  - Reproductive concerns of women treated with radical trachelectomy for cervical
      cancer.
AB  - OBJECTIVE: To report the reproductive concerns of women treated for stage I
      cervical cancer with fertility-preserving surgery. MATERIALS AND METHODS: Newly
      diagnosed cervical cancer patients undergoing radical trachelectomy were enrolled
      in this study preoperatively and assessed over time. Preliminary data from the
      preoperative analysis and 3-month and 6-month assessment points addressing
      reproductive concerns are presented. RESULTS: Between February 2004 and June
      2006, 29 patients were enrolled in the study. Three patients were excluded
      because they did not undergo the planned surgery and 6 patients were excluded
      because they required adjuvant therapy. Future childbearing was the main reason
      most women chose to undergo the procedure; however, treatment choice was also
      guided by conversations with their doctors (41%, n=12). Twenty-six (90%)
      initially expressed concern over future conception and childbearing, but this
      increased to all patients by 6 months. At enrollment, the majority of the
      patients had high expectations for future conception and childbearing but this
      declined over time. Despite this, patients' distress gradually decreased over
      time. CONCLUSIONS: Our results show that many women who have undergone a radical
      trachelectomy present with distress and reproductive concerns that persist for up
      to 6 months postoperatively. Concerns about conception appear to decrease
      following surgery; however, concerns about pregnancy appear to increase post
      trachelectomy itself. This pilot study reflects the first preliminary data from
      an active ongoing study prospectively collecting information over 2 years from
      newly diagnosed stage I cervical cancer patients undergoing radical
      trachelectomy.

PMID- 17188346
TI  - An electrophysiological investigation of semantic and phonological processing in
      skilled and less-skilled comprehenders.
AB  - The most prominent theories of reading consider reading comprehension ability to
      be a direct consequence of lower-level reading skills. Recently however, research
      has shown that some children with poor comprehension ability perform normally on
      tests of lower-level skills (e.g., decoding). One promising line of behavioral
      research has found semantic processing differences between good and poor
      comprehenders and suggests that impoverished semantic ability may be linked to
      poor comprehenders' difficulties. In the current study, we used event related
      potentials (ERP) to compare adult skilled and less-skilled comprehenders on a set
      of semantic and phonological processing tasks. The results revealed that the N400
      component of the ERP and the P200 component were sensitive to differences between
      skilled and less-skilled comprehenders during a semantic processing task.
      Importantly, skilled and less-skilled comprehenders showed no differences in
      their ERP response during a phonological processing task. These findings provide
      neurophysiological support for the hypothesis that less-skilled comprehenders
      have a weakness in semantic processing that may contribute to their comprehension
      difficulties.

PMID- 17188345
TI  - The regulation of alcohol intake by melanin-concentrating hormone in rats.
AB  - Given into the brain, melanin-concentrating hormone (MCH) increases alcohol
      consumption, but the mechanism and physiological relevance of this effect are
      unclear. We hypothesized that endogenous MCH will enhance alcohol drinking and
      that MCH increases alcohol's reinforcing properties. An MCH receptor 1 (MCHR1)
      antagonist, or saline was administered centrally alone, or preceding MCH or
      saline to rats trained to drink 10% alcohol using sucrose fading. Blocking MCHR1
      neither reduced alcohol intake (saline=0.4+/-0.1 g, 30 microg MCHR1
      antagonist=0.4+/-0.1 g/kg alcohol), nor attenuated MCH-induced alcohol drinking
      (MCHR1 antagonist/saline=0.7+/-0.1 g/kg, MCHR1 antagonist/MCH=0.9+/-0.1 g/kg
      alcohol). Another cohort of rats was trained to lever press for alcohol on a
      progressive ratio schedule. MCH or saline was administered centrally and lever
      presses were measured. MCH had no effect prior to the break point, but increased
      total responding during the session (saline=87.2+/-32.0, MCH=315.4+/-61.0
      presses). In conclusion, these data suggest that MCH augments alcohol drinking
      partly by enhancing the drug's reinforcing value. Further, endogenous MCH does
      not seem to regulate alcohol drinking, however because the antagonist failed to
      attenuate MCH-induced alcohol intake this conclusion is tentative.

PMID- 17188347
TI  - Structural and thermodynamic properties of starches extracted from GBSS and GWD
      suppressed potato lines.
AB  - A combined DSC-SAXS approach was employed to study the effects of amylose and
      phosphate esters on the assembly structures of amylopectin in B-type polymorphic
      potato tuber starches. Amylose and phosphate levels in the starches were
      specifically engineered by antisense suppression of the granule bound starch
      synthase (GBSS) and the glucan water dikinase (GWD), respectively. Joint analysis
      of the SAXS and DSC data for the engineered starches revealed that the sizes of
      amylopectin clusters, thickness of crystalline lamellae and the polymorphous
      structure type remained unchanged. However, differences were found in the
      structural organization of amylopectin clusters reflected in localization of
      amylose within these supramolecular structures. Additionally, data for annealed
      starches shows that investigated potato starches possess different types of
      amylopectin defects. The relationship between structure of investigated potato
      starches and their thermodynamic properties was recognized.

PMID- 17188348
TI  - Platelet adhesion to human umbilical vein endothelial cells cultured on anionic
      hydrogel scaffolds.
AB  - In this work we describe experiments designed to understand the human platelet
      adhesion to human umbilical vein endothelial cells (HUVECs) cultured on various
      kinds of chemically cross-linked anionic hydrogels, which were synthesized by
      radical polymerization. HUVECs could proliferate to sub-confluent or confluent on
      poly(acrylic acid) (PAA), poly(2-acrylamido-2-methyl-propane sulfonic acid sodium
      salt) (PNaAMPS), and poly(sodium p-styrene sulfonate) (PNaSS) gels. The
      proliferation behavior was not sensitive to the cross-linker concentration of the
      gels. However, the platelet adhesion on the HUVECs cultured on these gels showed
      different behavior, as revealed by human platelet adhesion test in static
      conditions. Only a few platelets adhered on the HUVEC sheets cultured on PNaAMPS
      gels with 4 and 10mol% cross-linker concentrations, and completely no platelet
      adhered on the HUVEC sheets cultured on PNaSS gels with 4 and 10mol% cross-linker
      concentrations. On the other hand, a large number of platelets adhered on the
      HUVECs cultured on PAA gels with 1, 2mol% cross-linker concentrations and PNaAMPS
      gel with 2mol% cross-linker concentration. Furthermore, the study showed that
      promote of the glycocalyx of HUVECs with transforming growth factor-beta(1) (TGF
      beta(1)) decreased platelet adhesion, and degrade the glycocalyx with heparinase
      I increased platelet adhesion. The results suggested that the glycocalyx of
      cultured HUVECs modulates platelet compatibility, and the amount of glycocalyx
      secreted by HUVECs dependents on the chemical structure and cross-linker
      concentration of gel scaffolds. This result should be applied to make the hybrid
      artificial blood vessel composes of gels and endothelial cells with high platelet
      compatibility.

PMID- 17188349
TI  - Coronary stents: a materials perspective.
AB  - The objective of this review is to describe the suitability of different
      biomaterials as coronary stents. This review focuses on the following topics: (1)
      different materials used for stents, (2) surface characteristics that influence
      stent-biology interactions, (3) the use of polymers in stents, and (4) drug
      eluting stents, especially those that are commercially available.

PMID- 17188350
TI  - Functional and histological evaluation of transplanted pancreatic islets
      immunoprotected by PEGylation and cyclosporine for 1 year.
AB  - Pancreatic islet transplantation is one of the most promising strategies for
      patients suffering from type 1 diabetes mellitus, but several therapeutic
      immunosuppressive medications must be administered simultaneously to protect
      transplanted islets in the long-term, and these expose patients to the risk of
      serious complications. Thus, we developed chemically modified islets with a
      protective poly(ethylene glycol) (PEG) layer, which reduces immunogenicity by
      preventing cellular immune reactions. We report here that PEG-based chemical
      immunomodulation can provide a semi-permanent effective therapy that protects
      transplanted islets at least for 1 year when accompanied by cyclosporine.
      Moreover, this combinatorial approach appears to avoid the toxicities associated
      with immunosuppressive medications because of the reduced amounts of medication
      required. Also, the conjugated PEG molecules were found to be continuously
      present at the transplanted islets. However, unmodified islets (control) were
      completely eliminated within 2 weeks even when CsA was administered. These
      results strongly suggest that this new combinatorial therapy provides a semi
      permanent, effective clinical means of attenuating transplanted islet
      immunogenicity for a long time, whilst avoiding the toxicities associated with
      therapeutic levels of immunosuppressants owing to the minimized
      immunosuppressant.

PMID- 17188351
TI  - Implantation in the macaque: expansion of the implantation site during the first
      week of implantation.
AB  - Data accumulated over several years of investigating implantation in macaque
      monkeys have been used to estimate the rate of expansion of the initial
      implantation site, the increase in volume of the site, and the rate of arterial
      invasion by cytotrophoblast columns. In addition the expansion of the secondary
      implantation site has also been estimated. The primary implantation site expands
      from an average diameter of 0.268 mm on day 10 to 4.93 mm on day 16-17. It
      expands in thickness from 0.064 mm on day 10 to 0.96 mm on day 16-17, and in
      volume from 0.0036 mm(3) on day 10 to 18.34 mm(3) on day 16-17. During this
      period of rapid expansion in extent and volume of the implantation site,
      trophoblast invades the endometrium, forms a lacunar stage, and initiates villus
      formation; consequently these very considerable changes in structure occur when
      the implantation is still very small yet growing rapidly. The secondary site
      expands from 0.23 mm in diameter on day 12 to 2.8mm on day 17. The rate of
      penetration of cytotrophoblast into endometrial arteries diminishes from 0.602 mm
      per day on day 12 to 0.171 mm per day on day 16, using the straight-line method
      of estimation. This diminution in rate is consistent with the hypothesis that
      cytotrophoblast cells generated at the anchoring villi migrate over
      cytotrophoblast cells that have attached to the endothelium of the endometrial
      arteries in advancing the intraluminal columns of trophoblast. It is hoped that
      the summaries provided will be useful to investigators using macaque monkeys to
      analyze aspects of implantation in primates.

PMID- 17188352
TI  - Impact of visceral involvements and blood cell count abnormalities on survival in
      adult T-cell leukemia/lymphoma (ATLL).
AB  - Multiple visceral involvements and various blood cell count abnormalities are
      frequently manifested in adult T-cell leukemia/lymphoma (ATLL) at diagnosis. We
      evaluated the effects of four visceral involvement (bone marrow (BM), skin,
      liver, spleen) and six blood cell count abnormalities (anemia, neutrophilia,
      thrombocytopenia, monocytosis, eosinophilia, basophilia) on the overall survival
      of 168 ATLL patients. In the aggressive type, BM involvement, skin involvement
      and monocytosis were significantly poor prognostic factors. Furthermore,
      concomitant involvement of BM and additional visceral organs worsened the
      prognosis. These data support that multiple organ involvements represent a poor
      prognostic factor for ATLL and provide clinical significance for BM examinations.

PMID- 17188353
TI  - Immature and mature monocyte-derived dendritic cells in myelodysplastic syndromes
      of subtypes refractory anemia or refractory anemia with ringed sideroblasts
      display an altered cytokine profile.
AB  - Dendritic cells (DC) are pivotal for T cell-mediated immunity. We investigated
      the early and terminal maturation of monocyte-derived DC (MoDC) in
      myelodysplastic syndromes (FAB subtypes refractory anemia (MDS-RA) or refractory
      anemia with ringed sideroblasts (MDS-RARS)). Immature MoDC were obtained by
      culture of monocytes with GM-CSF and IL-4 for 8 days. To obtain mature MoDC, TNF
      alpha was added during the final three culture days. T cell proliferation and T
      cell cytokine secretion in mixed lymphocyte reactions (MLR) unveiled a strong
      reduction of allostimulatory capacity of mature but also of immature MoDC from
      MDS patients. Immature MoDC from MDS patients exhibited an almost normal
      immunophenotype, but secreted substantially less IL-12 and more IL-10 in response
      to LPS/IFN-gamma than normal controls. Terminal addition of TNF-alpha to GM
      CSF/IL-4 treated monocytes failed to extinguish cytokine production by MDS MoDC
      and failed to induce the expected membrane upregulation of costimulatory and
      other ligands as in normal controls. While our data provide further support for
      previous studies that have indicated an impaired differentiation of immature
      towards mature MoDC, they also clearly demonstrate a qualitatively and
      quantitatively altered cytokine secretion at the level of immature MoDC, which
      may in part explain the reduced allostimulatory capacity of these cells. These
      alterations may contribute to immune modulation of the clinical phenotype of
      marrow failure in MDS, and may have to be considered when designing DC-based
      immunotherapeutic strategies for MDS.

PMID- 17188354
TI  - Protein expression profiling of the shrimp cellular response to white spot
      syndrome virus infection.
AB  - To better understand the pathogenesis of white spot syndrome virus (WSSV) and to
      determine which cell pathways might be affected after WSSV infection, two
      dimensional gel electrophoresis (2-DE) was used to produce protein expression
      profiles from samples taken at 48 h post-infection (hpi) from the stomachs of
      Litopenaeus vannamei (also called Penaeus vannamei) that were either specific
      pathogen free or else infected with WSSV. Seventy-five protein spots that
      consistently showed either a marked change (>50%) in accumulated levels or else
      were highly expressed throughout the course of WSSV infection were selected for
      further study. After in-gel trypsin digestion followed by LC-nanoESI-MS/MS,
      bioinformatics databases were searched for matches. A total of 53 proteins were
      identified, with functions that included energy production, calcium homeostasis,
      nucleic acid synthesis, signaling/communication, oxygen carrier/transportation,
      and SUMO-related modification. 2-DE results were shown to be consistent with
      relative EST database data from a previously developed EST database of two
      Penaeus monodon cDNA libraries. For seven selected genes, 2-DE and EST data were
      also compared with transcriptional time-course RT-PCR data. This study is the
      first global analysis of differentially expressed proteins in WSSV-infected
      shrimp, and in addition to increasing our understanding of the molecular
      pathogenesis of this virus-associated shrimp disease, the results presented here
      should be useful both for identifying potential biomarkers and for developing
      antiviral measures.

PMID- 17188355
TI  - PFOS levels in the blood and liver of a small insectivorous songbird near a
      fluorochemical plant.
AB  - Perfluorooctane sulfonate (PFOS) is the stable end product of the degradation of
      various perfluorinated compounds and is the predominant compound found in the
      environment and biota. PFOS is a widespread environmental contaminant that is
      found in a great diversity of wildlife species with more elevated tissue
      concentrations in animals from populated and industrialized areas. In this study
      we determined the PFOS accumulation in blood and livers of a small songbird, the
      great tit (Parus major), in the vicinity of a large fluorochemical plant in
      Antwerp, Belgium. PFOS concentrations ranged from 553 ng/g to 11359 ng/g in liver
      and ranged from 24 to 1625 ng/ml in blood, which are among the highest ever
      reported in free-living animals, and exceeded in almost all birds the hepatic
      benchmark concentrations for the protection of avian species [Beach SA, Newsted
      JL, Coady K, Giesy JP. Ecotoxicological evaluation of perfluorooctanesulfonate
      (PFOS). Rev Environ Contam Toxicol 2006;186:133-174]. Although PFOS
      concentrations in liver and blood decreased significantly within approximately
      5.5 km of the plant, differences were smaller than previously described for wood
      mice (Apodemus sylvaticus) and nestling great tits. PFOS concentrations in liver
      and blood were higher in young birds (<one-year old) than in older birds (>one
      year old). No significant sex differences were found. A highly significant
      correlation between liver and blood concentrations indicates the usefulness of
      blood as a non-destructive matrix for biomonitoring purposes.

PMID- 17188357
TI  - Non-MHC ligands for inhibitory immune receptors: novel insights and implications
      for immune regulation.
AB  - Regulation of cellular responses by inhibitory receptors is crucial for proper
      function of the immune system. The prototype inhibitory immune receptors are
      major histocompatibility complex (MHC) class I binding killer-Ig like receptors
      (KIRs) present on effector cells such as natural killer (NK) cells and effector T
      cells. However, the recent identification of non-MHC class I ligands for
      inhibitory immune receptors, such as KLRG1, KLRB1 and LAIR-1, indicates that also
      MHC class I-independent inhibitory immune receptors play crucial roles in
      inducing peripheral tolerance. The presence of these receptors on many other
      immune cell types besides effector cells suggests that tight regulation of cell
      activation is necessary in all facets of the immune response in both normal and
      diseased tissue. Here, we review novel insights and implications of non-MHC class
      I ligand binding to inhibitory immune receptors. We give an overview of the known
      ligand-receptor pairs by grouping the ligands according to their properties and
      discuss implications of these interactions for the maintenance of immune balance
      and for the defense against tumors and pathogens.

PMID- 17188356
TI  - Evaluation of the aerobic biodegradation of trichloroethylene via response
      surface methodology.
AB  - Response surface methodology (RSM) was used to evaluate the effect of additives
      for enhancing the aerobic biodegradation of trichloroethylene (TCE). The
      parameters investigated include the initial TCE concentration, addition of extra
      bacteria, use of toluene as an inducer and hydrogen peroxide as terminal electron
      acceptor (TEA). Without additive, degradation efficiencies of >or=80% were
      obtained for TCE concentrations<700 mg/L. According to the second-order
      polynomial RSM and biodegradation results, the use of toluene to induce enzyme
      production inhibited degradation at TCE concentrations<300 mg/L. The addition of
      hydrogen peroxide did improve the overall degradation efficiency but decreased
      the degradation rate. The RSM model for toluene, extra bacteria and TEA predicted
      that the best approach to optimize degradation of high TCE concentrations is to
      ensure adequate population in conjunction with supplemental TEA.

PMID- 17188358
TI  - Interaction between cisplatin treated murine peritoneal macrophages and L929
      cells: involvement of adhesion molecules, cytoskeletons, upregulation of Ca2+ and
      nitric oxide dependent cytotoxicity.
AB  - Murine peritoneal macrophages on treatment with cisplatin (10 microg/ml) showed
      increased binding to L929 cells. Cisplatin treated macrophage on co-incubation
      with L929 cells form a distinct cytoplasmic contact between the two cells. The
      plasmalemmae of the two cells fuse over a large surface area. The formation of
      contact between the cisplatin treated macrophage and L929 cell results in the
      induction of apoptosis in L929 cell. Untreated macrophages did not form a contact
      with L929 cells and no apoptosis is observed in L929 cells. Immunofluorescence
      microscopical studies clearly show the participation of cytoskeleton and the
      adhesion molecules in the formation of contact between the two cells. Further, a
      significant enhancement of the expression of iNOS and cytosolic Ca2+ was observed
      in cisplatin treated macrophages co-incubated with L929 cells. Cisplatin treated
      macrophages produced significant amount of NO when co-incubated with L929 cells,
      while there was minimal production of NO by untreated macrophages co-incubated
      with L929 cells. Cisplatin treated macrophage-induced L929 cell death was NO
      dependent, since L-NMMA (500 microM) significantly inhibited the cytotoxicity of
      L929 cells. The addition of excess L-arginine (2mM) reversed the L-NMMA induced
      inhibition of NO production and L929 cell cytotoxicity.

PMID- 17188359
TI  - Suppression subtraction hybridization (SSH) and macroarray techniques reveal
      differential gene expression profiles in brain of sea bream infected with
      nodavirus.
AB  - Despite of the impact that viruses have on aquatic organisms, relatively little
      is known on how fish fight against these infections. In this work, the brain gene
      expression pattern of sea bream (Sparus aurata) in response to nodavirus
      infection was investigated. We used the suppression subtractive hybridization
      (SSH) method to generate a subtracted cDNA library enriched with gene transcripts
      differentially expressed after 1 day post-infection. Some of the ESTs from the
      infected tissues fell in gene categories related to stress and immune responses.
      For the reverse library (ESTs expressed in controls compared with infected
      tissues) the most abundant transcripts were of ribosomal and mitochondrial
      nature. Several ESTs potentially induced by virus exposure were selected for in
      vivo expression studies. We observed a clear difference in expression between
      infected and control samples for two candidate genes, ubiquitin conjugating
      enzyme 7 interacting protein, which seems to play an important role in apoptosis
      and the interferon induced protein with helicase C domain 1 (mda-5) that
      contributes to apoptosis and regulates the type I IFN production, a key molecule
      of the antiviral innate response in most organisms.

PMID- 17188360
TI  - Effect of laser trabeculoplasty on nocturnal intraocular pressure in medically
      treated glaucoma patients.
AB  - PURPOSE: To evaluate the effects of laser trabeculoplasty on 24-hour intraocular
      pressure (IOP) in a group of medically treated open-angle glaucoma patients.
      DESIGN: Prospective experimental study. PARTICIPANTS: Eighteen open-angle
      glaucoma patients. METHODS: Laser trabeculoplasty (180 degrees ) was performed on
      28 eyes of 18 glaucoma patients. Twenty-four-hour IOP data were collected in a
      sleep laboratory before and 45 to 80 days after the procedure. Measurements of
      sitting and supine IOP were taken during the 16-hour diurnal/wake period, and
      measurements of supine IOP were taken during the 8-hour nocturnal/sleep period in
      2-hour intervals. MAIN OUTCOME MEASURES: Changes in the mean, peak, and range of
      IOP during the office-hour, diurnal, nocturnal, and 24-hour periods. RESULTS:
      Compared with the baselines, changes in the mean, peak, and range of IOP were not
      significant during the office-hour period and during the diurnal period in either
      the sitting or the supine position. The mean, peak, and range of IOP were reduced
      significantly during the nocturnal period in the supine position. Mean and peak
      24-hour IOP were reduced significantly in the habitual body positions (sitting
      during the diurnal period and supine during the nocturnal period). The reduction
      of mean 24-hour IOP in the supine position also was significant. CONCLUSIONS: In
      this group of medically treated open-angle glaucoma patients, laser
      trabeculoplasty reduced IOP more consistently during the nocturnal period than
      during the diurnal period.

PMID- 17188361
TI  - Optical analysis of visual improvement after correction of anisometropic
      amblyopia with a phakic intraocular lens in adult patients.
AB  - PURPOSE: To analyze possible reasons for an increase in visual acuity observed in
      myopic patients with anisometropic amblyopia after implantation of a phakic
      intraocular lens (PIOL) using a theoretical eye model. DESIGN: Retrospective case
      series. PARTICIPANTS: Fifty-nine eyes of 48 patients with anisometropic amblyopia
      implanted with an angle-supported PIOL. METHODS: Inclusion criteria were
      anisometropia of at least 3 diopters (D) and a best spectacle-corrected visual
      acuity (BSCVA) of 0.7 or less in the best eye. Follow-up was performed at 1, 3,
      6, and 12 months and then annually for up to 10 years. The theoretical analysis
      of mechanisms to explain the visual improvement was performed using a theoretical
      eye, based on the Kooijman model, in which the measured values of radii and
      thickness of the different surfaces were substituted. The magnification and spot
      size were calculated by a ray tracing process. MAIN OUTCOME MEASURES: Uncorrected
      visual acuity, improvement in best spectacle-corrected visual acuity, and
      spherical equivalent. RESULTS: Mean gain in visual acuity was 3 lines (range, 0-7
      lines). Fifty-four eyes (91.5%) gained at least 1 line of visual acuity, whereas
      no eyes lost lines of vision. The change in BSCVA did not correlate with
      preoperative BSCVA (Pearson coefficient, r = 0.19) or with the degree of
      anisometropia (Pearson coefficient, r = 0.23). The calculations using a Kooijman
      eye model corrected with spectacles and with a PIOL accounted for the full
      increase in visual acuity in terms of the magnification (increased by a factor of
      1.2) and the spot size (reduced by a factor of 2). CONCLUSIONS: After
      implantation of a PIOL, the visual acuity of myopic patients with anisometropic
      amblyopia showed a significant increase. This increase was explained using a
      theoretical eye model not only in terms of magnification but also including
      changes in aberrations. An evident role of neuroprocessing in this visual
      improvement was not identified.

PMID- 17188362
TI  - Modification of the active site of Mycobacterium tuberculosis KatG after
      disruption of the Met-Tyr-Trp cross-linked adduct.
AB  - Mycobacterium tuberculosis catalase-peroxidase (Mtb KatG) is a bifunctional
      enzyme that possesses both catalase and peroxidase activities and is responsible
      for the activation of the antituberculosis drug isoniazid. Mtb KatG contains an
      unusual adduct in its distal heme-pocket that consists of the covalently linked
      Trp107, Tyr229, and Met255. The KatG(Y229F) mutant lacks this adduct and has
      decreased steady-state catalase activity and enhanced peroxidase activity. In
      order to test a potential structural role of the adduct that supports catalase
      activity, we have used resonance Raman spectroscopy to probe the local heme
      environment of KatG(Y229F). In comparison to wild-type KatG, resting KatG(Y229F)
      contains a significant amount of 6-coordinate, low-spin heme and a more planar
      heme. Resonance Raman spectroscopy of the ferrous-CO complex of KatG(Y229F)
      suggest a non-linear Fe-CO binding geometry that is less tilted than in wild-type
      KatG. These data provide evidence that the Met-Tyr-Trp adduct imparts structural
      stability to the active site of KatG that seems to be important for sustaining
      catalase activity.

PMID- 17188363
TI  - Impact of a T cell-based blood test for tuberculosis infection on clinical
      decision-making in routine practice.
AB  - New T cell-based blood tests for tuberculosis infection could improve diagnosis
      of tuberculosis but their clinical utility remains unknown. We describe the role
      of the ELISpot test in the diagnostic work-up of 13 patients presenting with
      suspected tuberculosis in routine practice. Of the seven patients with a final
      diagnosis of active tuberculosis, all were positive by ELISpot including three
      with false-negative tuberculin skin test results. Rapid determination of
      tuberculosis infection by ELISpot accelerated the diagnosis of tuberculosis,
      enabling early treatment initiation.

PMID- 17188364
TI  - Unraveling the fundamental molecular mechanisms of morphological and cognitive
      defects in the irradiated brain.
AB  - Prenatal radiation exposure may have serious consequences for normal brain
      development. Results of epidemiological studies clearly pointed towards an
      increased risk of mental retardation in children of the surviving women of the
      Hiroshima/Nagasaki atomic bombing when in utero exposure had occurred between
      weeks 8 and 15 of pregnancy or, at a lower extend between weeks 15 and 25. The
      high sensitivity of the developing brain, in comparison to the adult brain is
      related to its higher number of non-differentiated, dividing neural precursor
      cells. Exposure of the developing brain to ionizing radiation can lead to three
      main outcomes in the developing brain, depending on the radiation dose and the
      elapsed period after irradiation. A first event occurs early after irradiation
      and triggers disturbances in cell proliferation, migration, differentiation, and
      cell death. A second event involves the generation of morphological abnormalities
      in the developing brain, if the radiation dose is sufficient. A third event
      involves cognitive dysfunctions that are a direct consequence from a disturbance
      in regional brain formation. The latter results from exposure to low doses and is
      usually only observed in the later period of development. In order to understand
      the mechanisms of radiation-induced cognitive dysfunctions, it is important to
      track back the underlying changes in specific molecular pathways. In this review,
      we present the possible relationships within and between molecular pathways
      potentially involved in cognitive dysfunctions induced by ionizing radiation in
      the developing brain.

PMID- 17188365
TI  - Does comorbid Social Anxiety Disorder impact the clinical presentation of
      principal Major Depressive Disorder?
AB  - BACKGROUND: Although previous research has examined comorbidity in principal
      Social Anxiety Disorder (SAD), few studies have examined the disorders for which
      those with comorbid SAD seek treatment. Further, studies have shown that
      depressive disorders often are associated with SAD, but few have examined the
      clinical characteristics of patients with this particular comorbidity. METHOD:
      The current study examined the prevalence of various principal Axis I disorders
      in 577 individuals diagnosed with comorbid SAD. RESULTS: Consistent with previous
      research, Major Depressive Disorder (MDD) was the most frequent principal
      diagnosis in patients with comorbid SAD. Those with principal MDD and comorbid
      SAD (MDD-SAD) were compared to those with MDD without SAD (MDD) on demographic
      and clinical characteristics. Patients with MDD-SAD versus those with MDD were
      more severe in terms of social functioning, duration of depressive episode,
      suicidal ideation, time out of work, presence of current alcohol
      abuse/dependence, and age of onset of MDD. Social functioning, duration of
      episode, suicidal ideation, and age of onset of MDD remained significant even
      after controlling for additional comorbid disorders. CONCLUSIONS: Findings
      suggest the need for future research to determine how treatments could be adapted
      for this commonly occurring comorbidity.

PMID- 17188366
TI  - The role of retrieval inhibition in the associative memory impairment of
      schizophrenia.
AB  - To examine retrieval-induced forgetting (RIF) in schizophrenia, subjects studied
      category-exemplar words taken from either strong or weak categories, and then
      practiced retrieval by completing category word-stems on half of the word pairs.
      Patients had reduced recall and recognition, but showed the expected RIF effect
      of better recall of unpracticed items from unpracticed categories than for
      unpracticed items from practiced categories. By contrast, patients and controls
      showed differing RIF for recognition as a function of categorical dominance:
      whereas controls showed RIF only for dominant category exemplar word pairs,
      patients showed RIF for both dominant and weak categories. Different patterns of
      baseline practiced retrieval for weak associate pairs in schizophrenia may
      explain this finding. The results failed to support faulty RIF in the associative
      memory impairment of schizophrenia.

PMID- 17188367
TI  - The microglial gene regulatory network activated by interferon-gamma.
AB  - We have analysed the microglial pathway stimulated by interferon-gamma (IFN
      gamma) using an in silico approach employing a database of eukaryotic molecular
      interactions and a microarray dataset validated by quantitative real-time PCR
      (qRT-PCR). Following IFN-gamma stimulation, production of neuroprotective factors
      by microglia was found to be reduced while caspase 1 and serping1 which are
      involved in cell death cascades are up-regulated suggesting a safeguarding
      mechanism. Extracellular matrix interactions and intracellular protein
      degradation are altered in concert with these changes. The regulatory network of
      IFN-gamma responsive microglial genes is outlined in detail and differentially
      expressed genes are mapped to their respective cellular compartments. A pathway
      approach to the analysis of microarray data is advocated since overlaying pathway
      and actual expression data as shown here greatly facilitates understanding the
      biological meaning of a gene regulatory network. In addition, genes of similar
      function that are differentially regulated are less likely to be false positives
      than single unrelated genes.

PMID- 17188368
TI  - Use of intraoperative ultrasound for localizing difficult parapharyngeal space
      abscesses in children.
AB  - While treatment of parapharyngeal and deep-space neck abscesses has progressed
      rapidly due to improvements in diagnostic imaging and medical therapy, surgical
      drainage remains the mainstay of treatment for larger and medically unresponsive
      abscesses. In many cases the intricate and delicate anatomy in children
      represents a challenging situation for the surgeon, particularly if he or she is
      not experienced in the care of the pediatric population. We present a novel idea
      used in the surgical management of parapharyngeal space abscesses in three
      children less that 6 years of age, in whom intraoperative ultrasound was used as
      an additional tool to locate and successfully drain the abscess.

PMID- 17188369
TI  - Adrenergic drugs modify the level of noradrenaline in the insular cortex and
      alter extinction of conditioned taste aversion in rats.
AB  - We compared the effect of conditioned taste aversion in rats by measuring the
      amount of sucrose that they drunk after conditioning, which differed according to
      whether rats had drunk the sucrose freely (SD: self drinking) during the
      conditioning session, or had been forced to drink it (IO: intra-oral
      administration through a chronically implanted cannula). The SD procedure delayed
      the extinction of conditioned taste aversion. Enhanced arousal, alertness,
      awareness or attention in the SD condition may have strengthened the memory of
      the taste. Brain noradrenergic networks are involved in such processes. We
      administered two noradrenergic drugs that produce opposite effects on
      noradrenaline release in the brain, methoxy-idazoxan, RX821002 (1mg/kg, i.p.),
      and guanfacine (0.12mg/kg, i.p.). We evaluated their effect (i) on the level of
      noradrenaline in the gustatory cortex using microdialysis, (ii) on glycaemia that
      is an essential factor of taste learning and (iii) on the comparative SD versus
      IO conditioned taste aversion protocol mentioned above. Injecting RX821001
      increased the level of noradrenaline in the gustatory cortex up to two-fold of
      the baseline. This effect lasted 1h. The same dose of RX821002 did not elicit any
      alteration of glycaemia. It enhanced extinction of conditioned taste aversion in
      the SD group of rats. Injecting 0.12mg/kg of guanfacine produced the opposite
      effect. The noradrenaline level of the gustatory cortex decreased, but only down
      to 20% of the baseline. This decrease lasted 2h. Guanfacine increased glycaemia.
      Extinction of conditioned taste aversion was only marginally decreased by
      guanfacine in the SD group of rats. These results fit with Aston-Jones' point of
      view that the role of the noradrenergic coeruleo-cortical system may be to
      enhance arousal, alertness, awareness or attention to an event by a transient
      increase of cortical noradrenaline.

PMID- 17188370
TI  - The involvement of transforming growth factor-beta1 secretion in urotensin II
      induced collagen synthesis in neonatal cardiac fibroblasts.
AB  - As the most potent vasoconstrictor in mammals, urotensin II (U II) has recently
      been demonstrated to play an important role in adverse cardiac remodeling and
      fibrosis. However, the mechanisms of U II-induced myocardial fibrosis remain to
      be clarified. We postulated that U II alters transforming growth factor-beta1
      (TGF-beta1) expression, and thereby modulates cardiac fibroblast collagen
      metabolism. Experiments were conducted using cardiac fibroblast from neonatal
      Wistar rats to determine the expression of TGF-beta1, and the role of U II
      receptor UT in this process. The functional role of TGF-beta1 and UT in
      modulating U II effects on type I, III collagen mRNA expression and 3H-proline
      incorporation was also analyzed. TGF-beta1 gene and protein expression were
      consistently identified in quiescent cardiac fibroblasts. U II increased the
      expression of TGF-beta1 mRNA and protein in a time-dependent manner. This effect
      was UT mediated, because UT antagonist urantide abolished U II-induced TGF-beta1
      expression. U II-induced increase in type I, III collagen mRNA expression and 3H
      proline incorporation were both inhibited by a specific TGF-beta1 neutralizing
      antibody and UT receptor antagonist urantide. Hence, our results indicate that
      TGF-beta1 is upregulated in cardiac fibroblasts by U II via UT and modulates
      profibrotic effects of U II. These findings provide novel insights into U II
      induced cardiac remodeling.

PMID- 17188371
TI  - Pigment epithelium-derived factor in ulcerative colitis: possible relationship
      with disease activity.
AB  - OBJECTIVES: Pigment epithelium-derived factor (PEDF) is an endogenous most
      potential angiogenic inhibitor and increased expression of PEDF in intestinal
      mucosa specimens was shown in the course of ulcerative colitis (UC). The aim of
      the present study was to evaluate serum concentration of pigment epithelium
      derived growth factor, a potent anti-angiogenic factor and its possible
      association with vascular endothelial growth factor (VEGF) levels and disease
      activity. METHODS: Concentrations of PEDF and VEGF were measured in sera of 33
      patients (13 females and 20 males) with active UC. RESULTS: There was significant
      increase of serum PEDF (32.3+/-2.9 vs. 20.6+/-4.7 ng/mL, P<0.05) as well as VEGF
      (326.4+/-58.1 vs. 110.9+/-15.7 pg/mL, P<0.05) in UC patients compared to healthy
      controls. Serum PEDF showed strong, positive correlation with endoscopic score
      (r=0.622, P<0.001), while such association was absent in respect to VEGF (r=0.05,
      P=0.77). In contrast serum VEGF decreased in severe UC comparing to patients with
      a mild course of disease, however the difference was not significant (274.9+/
      64.9 vs. 360.4+/-103.4 pg/mL, P=0.53). CONCLUSIONS: Increase in serum PEDF during
      UC, especially in severe forms of disease suggests its involvement in UC
      pathogenesis.

PMID- 17188372
TI  - Melanocortin-3 receptor activates MAP kinase via PI3 kinase.
AB  - HEK 293 cells stably expressing human melanocortin-3 receptor (MC3R) were exposed
      to melanocortin receptor agonist, NDP-MSH (10(-)(10)-10(-)(6) M). ERK1/2 was
      phosphorylated in a dose-dependent manner with an EC(50) of 3.3+/-1.5 x 10(-)(9)
      M, similar to the IC(50) of NDP-MSH binding to the MC3R. ERK1/2 phosphorylation
      was blocked by the melanocortin receptor antagonists SHU9119. NDP-MSH-induced
      ERK1/2 phosphorylation was sensitive to pertussis toxin and the PI3K inhibitor,
      wortmannin. Rp-cAMPS, BAPTA-AM and Myr-PKC did not inhibit the NDP-MSH-induced
      ERK1/2 phosphorylation. NDP-MSH stimulated cellular proliferation in a dose
      dependent manner with a similar EC(50) to ERK1/2 phosphorylation, 2.1+/-0.6 x 10(
      )(9) M. Cellular proliferation was blocked by AGRP (86-132) and by the MEK
      inhibitor, PD98059. The NDP-MSH did not inhibit serum deprivation-induced
      apoptosis. MC3R activation induces ERK1/2 phosphorylation via PI3K and this
      pathway is involved in cellular proliferation in HEK cells expressing MC3R.

PMID- 17188373
TI  - Role of endogenous nitric oxide in classic preconditioning in rat hearts.
AB  - Ischemic preconditioning (IPC) protects the heart against subsequent sustained
      ischemia reperfusion (RP). Despite many triggers and signaling pathways, which
      seem to be involved in IPC, the IPC-mechanisms remain a controversial issue. One
      of them is endogenous production of nitric oxide (NO). To assess the role of NO
      in IPC and its relation with glycogen and glycolysis, the effects of inhibiting
      NO synthase with L-NAME (50 microM) were examined in IPC rat hearts perfused with
      medium containing 10 mM glucose. Left ventricular developed pressure-rate product
      (RPP) and end diastolic pressure (EDP), lactate and glycogen contents, and cell
      viability were measured. Global ischemia (25 min) was followed by 30 min RP. IPC
      consisted in one cycle of 3 min ischemia-5 min RP. IPC reduced EDP and improved
      RP recovery of RPP. L-NAME had no effects on the non-IPC group but abolished
      these effects of IPC. IPC reduced ischemic decrease of glycogen and the
      acceleration of glycolysis, and improved cell viability. L-NAME did not affect
      these effects of IPC. The results suggest that NO is ineffective on the noxious
      effects of ischemia-RP in non-IPC hearts and on the effects of IPC on cell
      viability, glycogenolysis and glycolysis whereas it is only involved in
      functional protection.

PMID- 17188374
TI  - ERK implication in cell cycle regulation.
AB  - The Ras/Raf/MEK/ERK signaling cascade that integrates an extreme variety of
      extracellular stimuli into key biological responses controlling cell
      proliferation, differentiation or death is one of the most studied intracellular
      pathways. Here we present some evidences that have been accumulated over the last
      15 years proving the requirement of ERK in the control of cell proliferation. In
      this review we focus (i) on the spatio-temporal control of ERK signaling, (ii) on
      the key cellular components linking extracellular signals to the induction and
      activation of cell cycle events controlling G1 to S-phase transition and (iii) on
      the role of ERK in the growth factor-independent G2/M phase of the cell cycle. As
      ERK pathway is often co-activated with the PI3 kinase signaling, we highlight
      some of the key points of convergence leading to a full activation of mTOR via
      ERK and AKT synergies. Finally, ERK and AKT targets being constitutively
      activated in so many human cancers, we briefly touched the cure issue of using
      more specific drugs in rationally selected cancer patients.

PMID- 17188375
TI  - Reactive hyperemic pre-ejection shear stress of brachial artery determines
      endothelial function in patients with untreated essential hypertension.
AB  - The aim of this study was to identify which phase of wall shear stress (SS)
      augmentation during reactive hyperemia (RH) is the crucial determinant of
      endothelial reactivity. Fifty-three patients with untreated essential
      hypertension were enrolled. A 7.5-MHz linear array transducer was used to record
      the 2D images and Doppler flow signals of brachial artery at baseline and during
      RH. Wall SS and flow-mediated vasodilation were calculated sequentially. The
      result of this study demonstrated that augmentation of wall SS at end-diastolic
      phase during peak RH is the main rheologic determinant of endothelial function in
      patients with untreated essential hypertension.

PMID- 17188376
TI  - Prognosis of left ventricular hypertrabeculation/noncompaction is dependent on
      cardiac and neuromuscular comorbidity.
AB  - BACKGROUND AND OBJECTIVES: Left ventricular hypertrabeculation/noncompaction
      (LVHT) is a cardiac abnormality frequently associated with neuromuscular
      disorders (NMD). The data about long-term prognosis of patients with LVHT are
      controversial. Aim of the study in a cohort of LVHT patients was to assess the
      long-term prognosis regarding mortality, cardiac and neuromuscular comorbidity.
      METHODS AND RESULTS: In 86 patients LVHT was diagnosed echocardiographically
      between June 1995 and December 2004 (21 female, mean age 52 +/- 14, range 14-94
      years). All patients underwent a baseline cardiologic investigation and were
      invited for a neurologic investigation. A specific NMD was diagnosed in 21, a NMD
      of unknown etiology in 33, the neurologic investigation was normal in 13 and 19
      patients refused. During a mean follow-up of 51 months (range 3-106 months) the
      mortality rate was 5.3%/year. Predictors for an increased mortality were
      increased age (p=0.0134), presence of NMD (p=0.0324), exertional dyspnoea
      (p=0.0329), edema (p=0.0049), heart failure (p=0.0048), left anterior hemiblock
      (p=0.0078) and a left ventricular fractional shortening <25% (p=0.0648).
      CONCLUSION: The mortality of LVHT in adult patients depends on cardiac and
      neurologic comorbidity. Predictors for mortality are increased age, neuromuscular
      disorder, heart failure, left ventricular dilatation and systolic dysfunction.

PMID- 17188377
TI  - Clinical investigation: Utility of left ventricular end diastolic diameter in the
      prediction of susceptibility to ventricular tachyarrhythmias.
AB  - BACKGROUND: Prior studies have shown the utility of using both QRS duration and
      QT dispersion (QTd) as predictors of risk for ventricular tachyarrhythmias (VA).
      Lengthening of the QRS duration represents dyssynchrony of regional myocardial
      wall contraction, and increased QTd similarly represents variations in myocardial
      repolarization. We sought to examine the left ventricular end diastolic diameter
      (LVEDD) as a predictor of VA susceptibility. METHODS: Eighty-eight patients
      referred for electrophysiologic (EP) studies were evaluated. EP testing was
      performed using a standard protocol of up to three extrastimuli. QTd and QRS
      duration analyses were performed in a blinded manner. Values were defined as
      abnormal if QRS duration>120 ms, QTd>60 ms, and LVEDD>6 cm. RESULTS: Of 88
      patients (65 males; 23 females; mean age 67+/-15 years), 33 were inducible by EP
      testing. Patients with either increased QRS duration or QTd are shown to be at
      greater risk for VA inducibility. LVEDD is a strong predictor of inducibility for
      VA (p<0.02 between inducible and non-inducible patients). LVEDD in combination
      with QRS duration and QTd, further strengthens predictability for VA (p<0.03 for
      QRS duration and p<0.02 for QTd) with a trend towards inducibility as each value
      increases. Combination of the three parameters of QRS duration, QTd, and LVEDD
      was 91% sensitive for the identification of those patients inducible for VA.
      CONCLUSION: The LVEDD is an echocardiographic value that strongly predicts VA
      inducibility, and when combined with QRS duration and QTd, identifies patients at
      higher risk for these tachyarrhythmias.

PMID- 17188378
TI  - The emerging anti-inflammatory role of HDL-cholesterol, illustrated in
      cardiovascular disease free population; the ATTICA study.
AB  - OBJECTIVE: In this work we assessed the relationship between HDL-cholesterol
      levels and various inflammation markers status in a sample of cardiovascular
      disease free adult men and women from Greece. METHODS: The ATTICA study is a
      population-based cohort that has randomly enrolled 1128 men and 1154 women (aged
      >18 years old), stratified by age-gender, from the greater area of Athens, during
      2001-2002. Adherence to Mediterranean diet was assessed through a diet-score that
      was based on a validated food-frequency questionnaire. In this study we assessed
      the relationship between HDL-cholesterol levels and inflammation markers (high
      sensitivity C-reactive protein, interleukin-6, homocysteine and amyloid-a), after
      taking into account the effect of several confounders. RESULTS: 46% of men and
      40% of women had total serum cholesterol levels >200 mg/dl, while 21% of men and
      7% of women had HDL-cholesterol levels <35 mg/dl. The mean value for HDL
      cholesterol was 53+/-14 mg/dl in females and 44+/-14 mg/dl in males. HDL
      cholesterol levels were inversely correlated to the hs-CRP levels (b=-0.028,
      P=0.001) and homocysteine levels (b=-0.039, P=0.036), after adjustment for sex,
      age, body mass index, physical activity status, smoking, total cholesterol
      levels, lipid lower agents, ethanol intake and diabetes mellitus; while no
      statistical significance was found between HDL-cholesterol levels and interleukin
      6 and serum amyloid-a. CONCLUSIONS: In this work we evaluated the inverse
      relationship between HDL-cholesterol levels and inflammatory markers in a sample
      adult cardiovascular disease free population. This study among others illustrates
      the anti-inflammatory emerging role of HDL-cholesterol in reducing cardiovascular
      risk.

PMID- 17188379
TI  - Is transesophageal echocardiography useful in planning surgery of mediastinal
      thymomas? Transesophageal investigation of a mediastinal thymoma.
AB  - Thymomas are the commonest tumors arising in the anterior mediastinum, sometimes
      representing an incidental finding at radiological examination. Surgery of these
      neoplasms must be planned after accurately assessing the invasive or non-invasive
      nature of the mass. In the present case this could be achieved also by submitting
      the patient to transesophageal echocardiography which could accurately exclude
      infiltration of heart walls. We therefore think that this technique can be
      considered a useful complement to radiological ones in defining the surgical
      strategy of mediastinal thymomas.

PMID- 17188380
TI  - Increased endothelial monocyte adhesiveness is related to clinical outcomes in
      chronic heart failure.
AB  - BACKGROUND: Vascular inflammation and endothelial dysfunction are evident in
      patients with chronic heart failure (CHF). We hypothesized that circulating
      peripheral blood mononuclear cells (PBMCs) may be activated and the resultant
      increased endothelial monocyte adhesion may be functionally and
      pathophysiologically relevant in CHF. In the present study, we investigated the
      clinical significance of the activity of PBMCs in patients with CHF. METHODS:
      PBMCs were isolated from 34 CHF patients, from 10 healthy volunteers (normal
      control group) and from 17 patients admitted for investigation of suspected
      coronary artery disease (disease control group). In each patient, the
      adhesiveness of PBMCs to cultured human aortic endothelial cells (HAECs) with or
      without tumor necrosis factor-alpha (TNF-alpha) stimulation was determined. Major
      adverse cardiac events (death, heart transplantation or hospitalization with
      worsening heart failure) were determined in the 34 CHF patients during a median
      follow-up period of 182 days. RESULTS: Compared with those from both control
      groups and from mild CHF patients, PBMCs isolated from severe CHF patients
      adhered more to the HAECs. The endothelial adhesiveness of PBMCs correlated
      positively with the circulating levels of CAMs and can supply prognostic
      information in CHF patients. The difference between event-free curves based on
      the median levels of endothelial-PBMC adhesion was significant (log rank test,
      p=0.0139). CONCLUSIONS: Endothelial adhesiveness of PBMCs is increased and
      correlated to clinical outcomes, and may be pathophysiologically relevant to the
      progression of CHF.

PMID- 17188381
TI  - Bayesian analysis to validate a commercial ELISA to detect paratuberculosis in
      dairy herds of southern Chile.
AB  - In Chile, Mycobacterium avium subsp. paratuberculosis (Map) has been isolated on
      several occasions and clinical cases have been reported. Nevertheless, diagnostic
      tests have not yet been validated for this agent in the Chilean setting. The
      objective of the study was to validate a commercial ELISA to detect Map shedding
      dairy cows in management conditions, prevalence and stages of infection existing
      in Southern Chile, utilising different statistical approaches. Blood and faeces
      were collected from 1333 lactating cows in 27 dairy herds (both large commercial
      and smallholder dairy farms) between September 2003 and August 2004. Within the
      herds up to a maximum of 100 dairy cows were selected based on age (>or=3 years
      old) and, if present, clinical signs of a Map infection. In herds with less than
      100 cows, all cows >or=3 years old were sampled. Blood samples were tested using
      a commercial ELISA kit (IDEXX Laboratories, Inc.). Faecal samples were cultured
      on Herrold's Egg Yolk Medium (HEYM). Latent class models (i.e. maximum likelihood
      (ML) methods and Bayesian inference) were used to determine the validity of the
      ELISA. Map was cultured from 54 (4.1%) cows and 10 (37.0%) herds, which were all
      large, commercial dairy herds. As a result of empty cells in the cross
      tabulations, the ML model provided the same results as the validation with faecal
      culture as the gold-standard. In the Bayesian model, the Se and Sp of the ELISA
      were estimated to be 26% (95% CI: 18-35%) and 98.5% (95% CI: 97.4-99.4%),
      respectively. For faecal culture, the Se was 54% (95% CI: 46-62%) and the Sp was
      100% (95% CI: 99.9-100%). Interestingly, the prevalence in the smallholder dairy
      farms was estimated to be 8% even though there were no faecal culture positive
      cows detected in those herds. There was no significant correlation between the
      two tests. The advantage of Bayesian inference is that the Se and Sp of both
      tests are obtained in one model relative to the (latent) true disease status, the
      model can handle small datasets and empty cells and the estimates can be
      corrected for the correlation between tests when the tests are not conditionally
      independent. Therefore, Bayesian analysis was the preferred method for Map that
      lacks a gold-standard and usually has low cow-level prevalence.

PMID- 17188382
TI  - Survival and breast relapse in 3834 patients with T1-T2 breast cancer after
      conserving surgery and adjuvant treatment.
AB  - PURPOSE: The aim of the present analysis is to determine the long-term results in
      terms of breast relapse and specific survival in patients treated with conserving
      surgery and adjuvant treatment for early breast cancer. METHODS: From January
      1980 to December 2001, 3834 patients with pT1-T2 breast cancer were treated
      consecutively at the University of Florence. The median age of the patient
      population was 55 years (range 30-80). All patients were followed for a median of
      7.4 years (range 0.6 year to 22.5 years). The crude probability of survival (or
      local recurrence) was estimated by using Kaplan-Meier method, and survival (or
      local recurrence) comparisons were carried out using Cox proportional hazard
      regression models. RESULTS: The Cox regression model by stepwise selection showed
      some parameters, such as chemotherapy (HR 1.53; CI 1.19-1.95), pT status (HR
      1.62, CI 1.31-2.01), positive axillary lymph nodes (HR 1.92, CI 1.66-2.22), and
      local recurrence (HR 4.58; CI 3.66-5.73), as independent prognostic factors for
      breast cancer death. Moreover, we found lower rate survival among patients
      treated before 1991 in comparison to women treated after 1991 (p=0.0001) probably
      due to inadequate treatment. For local disease free survival, age at presentation
      (HR 0.47; CI 0.35-0.63), use of tamoxifen (HR 0.42; CI 0.25-0.71), surgical
      margins (HR 2.00; CI 1.21-3.30), and chemotherapy (HR 0.53; CI 0.31-0.91) emerged
      by multivariate analyses as significant breast relapse predictors. CONCLUSION: In
      our experience breast conserving surgery followed by adjuvant radiotherapy
      treatment gives high rates of local control in women with early breast cancer.
      The use of routinely adjuvant chemotherapy and hormone therapy lowered the local
      recurrence and probably the modification of therapeutic approach in the last
      decades also improved the specific survival.

PMID- 17188383
TI  - Velocity-dependent EMG activity of masseter and sternocleidomastoideus muscles
      during a ballistic arm thrusting movement.
AB  - Two experiments were conducted to investigate the functional relationship between
      the general somatic motor function and the oral motor function. In Experiment 1,
      we analyzed the relationship between the amount of masseter muscle (MSS) activity
      and the velocity of a ballistic, 'karate-do' arm thrusting movement (ThrMov).
      ThrMov velocity was measured from video images taken with a high-speed CCD camera
      at a frequency of 500Hz. EMGs of MSS and sternocleidomastoideus (SCM) muscles as
      well as other related muscles were recorded simultaneously with video images in 6
      varsity 'karate-do' athletes. Pearson's correlation coefficients were calculated
      between EMG amplitude and movement velocity. EMG activity of MSS as well as the
      other muscles increased as a function of ThrMov velocity in all participants, as
      evidenced by highly significant (p<.01) correlation coefficients, ranging from
      .64 to .87 (mean: .75). MSS EMG activity attained during ThrMovs performed at
      maximum velocity ranged between 14.6% and 113.8% of this muscle's MVC (45.7+/
      39.3% MVC, mean+/-SD). SCM was also strongly active and closely associated with
      MSS. Besides changes in amount of EMG activity, it was further found that R-MSS
      EMG onset progressively shifted to the earlier phase of the ThrMov as ThrMov
      velocity increased. EMG onset time of R-MSS as well as R- and L-SCMs was
      negatively correlated with ThrMov velocity; when performed at maximum velocity
      MSS activation preceded the start of ThrMov by more than 100ms, whereas MSS was
      recruited last at approximately 150ms after the start of ThrMov when performed at
      moderate speed ( approximately 50% of maximum). In Experiment 2, the effects of
      head movement relative to the trunk on R-MSS and SCMs EMG activity were tested in
      both gazing and sidelong glancing conditions. A much smaller head rotation
      relative to the trunk was necessary during the ThrMov in the sidelong glancing
      condition compared to the gazing condition. R-MSS EMG activity was affected
      significantly by the difference between these conditions and decreased by 5.2%
      MVC in the sidelong glancing condition compared to the gazing condition. In
      association with the change in requirement for head movement between those
      conditions, EMG balance between the bilateral SCMs changed substantially.
      Finally, marked muscle activity during ThrMov was found in the MSS that was not
      directly involved in performing this movement, indicating a form of 'remote
      facilitation'.

PMID- 17188384
TI  - Brain distribution and molecular cloning of the bovine GABA rho1 receptor.
AB  - GABA(C) receptors were originally found in the mammalian retina and recent
      evidence shows that they are also expressed in several areas of the brain,
      including caudate nucleus, brain stem, pons and corpus callosum. In this study,
      plasma membranes from the caudate nucleus were microinjected into X. laevis
      oocytes. This led the oocyte plasma membrane to incorporate functional
      bicuculline-resistant, Cl(-) conducting bovine GABA receptors, similar to those
      of the retina. Immunolocalization of the GABA rho1 subunit revealed its
      expression in bovine neurons in the head of the caudate as well as in the olive,
      cuneiform and reticular nuclei of the brain stem. The same antibodies failed to
      show expression in the callosum and pons, where the GABA rho1 mRNA was previously
      detected. The cloned GABA rho1 sequence predicts a protein with 473 amino acids
      and 74-93% similarity to other GABA rho1 subunits. Oocytes injected with the cDNA
      express a non-desensitizing, homomeric receptor with a GABA EC(50)=6.0 microM and
      a Hill coefficient of 1.8. The results confirm the presence of GABA(C) receptor
      mRNAs in several areas of the mammalian brain and show that some of these areas
      express functional GABA rho1 receptors that have the classic GABA(C) receptor
      characteristics.

PMID- 17188385
TI  - Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress
      induced ACTH responses in conscious rats.
AB  - Orexins, recognized for their diverse functions in sleep/wakefulness/arousal and
      appetite regulation, may play provocative roles in stress response. Although the
      PVN of the hypothalamus expresses an abundance of orexin-2 receptor (OX-2R), the
      involvement of OX-2R in regulating ACTH response to stress remains unclear. To
      address this, we examined effects of a selective antagonist to OX-2R (N-{(1S)-1
      [6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]carbonyl}-2,2-dimethylpropyl)-N-{4
      pyridinylmethyl}amine upon plasma ACTH concentrations after administration of
      orexin A and swimming stress. Increases in ACTH levels with orexin A or swimming
      stress were attenuated with prior administration of an OX-2R antagonist. These
      results suggest that swimming stress facilitates ACTH release, at least in part
      via activation of OX-2R.

PMID- 17188386
TI  - Effect of water activity on thermal resistance of Salmonella krefeld in liquid
      medium and on rawhide surface.
AB  - The thermal resistivity of Salmonella krefeld at 60 and 65 degrees C as affected
      by water activity (0.99-0.60) was investigated in a liquid medium viz. Trypticase
      Soy Broth (TSB) and on rawhide surface. A reduction of the a(w) of the liquid
      medium resulted in an increase in the heat resistance of Salmonella krefeld. At a
      particular water activity the type of solute played a significant role with
      Salmonella krefeld exhibiting much higher heat sensitivity in the media with
      glycerol compared to the media with sucrose. The heat resistance of Salmonella
      krefeld inoculated onto the surface of rawhide was also investigated during hot
      air drying at 60 and 65 degrees C at two initial levels of a(w), 0.99 and 0.90,
      prior to drying as determined at 250 degrees C. The rate of water loss or a(w)
      decrease during drying was not significantly influenced by the initial water
      activity but was clearly dependent on the drying temperature with all survival
      curves displaying an upward concavity. Salmonella on rawhide with an initial a(w)
      of 0.90 exhibited higher heat tolerance than with an initial a(w) of 0.99 during
      a prolonged heating period with the initial a(w) significantly affecting the heat
      resistance particularly at higher drying temperatures.

PMID- 17188387
TI  - Antimicrobial and cytotoxic knotwood extracts and related pure compounds and
      their effects on food-associated microorganisms.
AB  - Knotwood or bark extracts prepared from 30 species of hard and soft wood trees as
      well as selected pure compounds (lignans, stilbenes and flavonoids) were assayed
      for their antimicrobial activity against a battery of both gram positive and
      negative bacteria, yeasts, and filamentous fungi (Bacillus cereus, Staphylococcus
      aureus, Listeria monocytogenes, Lactobacillus plantarum, Escherichia coli,
      Salmonella infantis, Pseudomonas fluorescens, Candida albicans, Saccharomyces
      cerevisiae, Aspergillus fumigatus and Penicillium brevicompactum). By far the
      most consistent antibacterial and antifungal properties were associated with
      extracts of Pinus species. These extracts showed also cytotoxicity against a
      mouse hepatoma cell line. Both antimicrobial and cytotoxic properties correlated
      with the stilbene content of the extracts. Purified stilbenes showed the most
      consistent antimicrobial and cytotoxic activities, while purified lignans had
      marginal effects, only. The results suggest that stilbenes account both for the
      antimicrobial and cytotoxic properties of Pinus knotwood extracts.

PMID- 17188389
TI  - Role of p38 map kinase in glycine-induced hepatocyte resistance to hypoxic
      injury.
AB  - BACKGROUND/AIMS: Glycine hepatoprotection is well known. However, the mechanisms
      involved are still poorly characterized. METHODS: Glycine protection was
      investigated in isolated rat hepatocytes pretreated with 2 mmol/L glycine 15 min
      before incubation under hypoxic conditions. RESULTS: Glycine significantly
      reduced Na+ overload and hepatocyte death caused by hypoxia. Glycine protection
      required the activation of a signal pathway involving Src, Pyk2 and p38 MAP
      kinases. Glycine treatment also induced a 11% increase of hepatocyte volume and
      transient ATP release. The prevention of cell swelling by hepatocyte incubation
      in a hypertonic medium as well as the degradation of extracellular ATP with
      apyrase or the block P2 purinergic receptors with suramin reverted glycine
      induced cytoprotection and inhibited Src, Pyk2 and p38 MAPK activation. Glycine
      down-modulated Na+/H+ exchanger (NHE) activity, without affecting the development
      of intracellular acidosis during hypoxia. Such an effect was reverted by
      inhibiting p38 MAPK that also abolished glycine protection against Na+ overload
      caused by hypoxia. CONCLUSIONS: Glycine-induced ATP release in response to a
      moderate hepatocyte swelling led to the autocrine stimulation of P2 receptors and
      to the activation of Src, Pyk2 and p38 MAPK that increased hepatocyte resistance
      to hypoxia by preventing Na+ influx through NHE.

PMID- 17188388
TI  - The renin-angiotensin system in a rat model of hepatic fibrosis: evidence for a
      protective role of Angiotensin-(1-7).
AB  - BACKGROUND/AIMS: The circulating renin-angiotensin system (RAS) [plasma renin
      activity (PRA), Angiotensin (Ang) I, Ang II and Ang-(1-7)] was evaluated in a
      model of hepatic fibrosis in rats. To investigate the pathophysiological
      involvement of Ang-(1-7), animals were treated with the Ang-(1-7) Mas receptor
      antagonist, A-779. METHODS: RAS components, liver function and histology were
      examined in male Wistar rats (220-300 g). Animals were submitted to sham-surgery
      or ligature of the bile duct and evaluated 1, 2, 4 and 6 weeks later. Blood
      samples were obtained to determine biochemical parameters and RAS components. A
      second group was treated with A-779 or vehicle to measure liver hydroxyproline
      and total transforming growth factor beta-1 (TGFbeta1). RESULTS: PRA and Ang I
      were significantly elevated in rats at 4 and 6 weeks compared to sham-operated
      animals. Ang II and Ang-(1-7) progressively increased over the 6 weeks. Changes
      in RAS profile correlated with histological signs of fibrosis and deterioration
      in liver function. Pharmacological blockade of the Ang-(1-7) receptor aggravated
      liver fibrosis with a significant elevation in hydroxyproline and total
      TGFbeta(1). CONCLUSIONS: Hepatic fibrosis was associated with RAS activation in
      our model. Our data also suggested that Ang-(1-7) played a protective role in
      hepatic fibrosis.

PMID- 17188390
TI  - Liver-homing of purified glucose oxidase: a novel in vivo model of physiological
      hepatic oxidative stress (H2O2).
AB  - BACKGROUND/AIMS: Reactive oxygen species (ROS), such as H2O2, are implicated in
      normal and pathological liver function. However, due to the lack of suitable in
      vivo models of ROS generation the (patho) physiological relevance of H2O2 remains
      controversial. METHODS: We established a novel model of sustained hepatic H2O2
      release using intravenous administration of purified Aspergillus niger glucose
      oxidase (GOX) in rats. RESULTS: GOX is rapidly cleared from the blood stream and
      almost exclusively localizes to Kupffer cells. GOX maintained its ability to
      generate H2O2 over 24h. While sublethal GOX doses induced hepatocellular
      necrosis, our morphological and functional studies show that lower levels of GOX
      which generate H2O2 comparable to release by inflammatory cells are non-toxic and
      do not induce histological inflammation. However, these non-toxic H2O2 levels
      increased oxidized glutathione and induced heme oxygenase 1 in the liver. In
      addition, several hepatocyte transporters were downregulated, while no decrease
      of bile formation, a sensitive marker of liver function, was observed.
      CONCLUSIONS: Our in vivo model allows to study the effects of extracellular H2O2
      in the liver as is released by inflammatory cells. Thus analysis of the role of
      this major ROS in the absence of confounding inflammatory cofactors will be
      possible.

PMID- 17188391
TI  - Expression of large tenascin-C splice variants by hepatic stellate
      cells/myofibroblasts in chronic hepatitis C.
AB  - BACKGROUND/AIMS: Earlier studies have suggested involvement of tenascin-C (TN-C)
      in liver fibrosis. Here, we examined expression of TN-C variants and types of
      alternatively spliced fibronectin-type III (FNIII) repeats in chronic hepatitis.
      METHODS: Using three monoclonal antibodies against TN-C variants,
      immunohistochemical staining was performed and the correlation with histological
      parameters of chronic hepatitis C was examined. The cellular source was also
      determined and variant expression and their types were tested using isolated rat
      hepatic stellate cells (HSCs), liver myofibroblasts, and/or LI90 cells. RESULTS:
      Large variants were not expressed in normal liver, but were up-regulated in
      chronic hepatitis, especially at sites of interface hepatitis and confluent
      necrosis, showing stronger correlations between staining intensity and these than
      with other parameters or fibrosis. TN-C deposition was closely correlated with
      increase in the number of alpha-smooth muscle actin-positive cells, i.e.
      activated HSCs/myofibroblasts, and in situ hybridization showed TN-C mRNA signals
      in the cells. Activated HSCs and myofibroblasts in culture highly expressed large
      variants of TN-C. In LI90 cells, sequencing of large variants revealed that the
      FNIII repeats D and A1/A4, followed by B, were preferentially included.
      CONCLUSIONS: TN-C and its variants are produced by HSCs/myofibroblasts,
      suggesting important roles in liver fibrogenesis.

PMID- 17188392
TI  - Up-regulation of fatty acid synthase promoter by hepatitis C virus core protein:
      genotype-3a core has a stronger effect than genotype-1b core.
AB  - BACKGROUND/AIMS: Hepatitis C virus genotype-3a (HCV-3a) is directly linked to
      steatosis development. We studied the effects of HCV-3a core protein on the
      promoter activity of fatty acid synthase (FAS), a major enzyme involved in de
      novo lipid synthesis. METHODS AND RESULTS: HCV-3a and -1b core genes were cloned
      and expressed. Using a FAS promoter-luciferase reporter, we demonstrated that
      both HCV-3a and -1b core proteins up-regulated the FAS promoter. However, HCV-3a
      core protein expression induced significantly higher FAS promoter activity than
      HCV-1b core. We further showed that FAS up-regulation by HCV core was dependent
      on transcription factor sterol response element binding protein-1. Mutational
      analysis showed that processing of HCV core protein of different genotypes was
      differentially involved in FAS promoter up-regulation. Although lipid droplet
      localization of HCV core protein was not important for FAS up-regulation, a
      specific amino acid residue (Phe(164)) within the FATG lipid droplet localization
      sequence of HCV-3a core protein played a major role in the stronger FAS
      activation by HCV-3a core. CONCLUSIONS: The stronger effect of HCV-3a core
      protein on FAS activation in comparison to HCV-1b core could contribute to the
      higher prevalence and severity of steatosis in HCV-3a infections.

PMID- 17188393
TI  - Amanita phalloides poisoning: reassessment of prognostic factors and indications
      for emergency liver transplantation.
AB  - BACKGROUND/AIMS: Amanita phalloides poisoning is an uncommon cause of acute liver
      failure with an especially rapid course. The aim of this study was to re-assess
      transplantation criteria in patients with mushroom poisoning. METHODS: Twenty
      seven patients admitted for Amanita phalloides poisoning were studied. Previously
      reported transplantation criteria, including the recent Ganzert's criteria, were
      tested retrospectively. RESULTS: The rate of fatal intoxication (death and/or
      transplantation) was 8/27 (30%). An interval between ingestion and diarrhea <8h
      was a very early predictor of a fatal outcome (accuracy of 78%). Later on, non
      paracetamol and paracetamol King's College criteria were superior to Clichy's and
      Ganzert's criteria (accuracy of 100% compared to 85% and 85%, respectively).
      Encephalopathy and renal insufficiency were not constant in the fatal
      intoxication group. Prothrombin index below 10% 4 days or more after ingestion
      had a 100% accuracy for predicting a fatal outcome. CONCLUSIONS: Liver
      transplantation should be strongly considered in patients with an interval
      between ingestion and diarrhea <8h. Encephalopathy should not be an absolute
      prerequisite for deciding transplantation. From day 4 after ingestion,
      prothrombin index lower than 10% ( approximately INR of 6) alone is a reliable
      tool for deciding emergency transplantation.

PMID- 17188394
TI  - The role of job satisfaction, job dissatisfaction and demographic factors on
      physicians' intentions to switch work sector from public to private.
AB  - This study is based on a unique data set for the years 1988-2003 and uses
      structural equation models to examine the impact of job satisfaction and job
      dissatisfaction on physicians' intention to switch from public- to private-sector
      work. In Finland, physicians who work primarily in a public-hospital or health
      centre setting can also run a private practice. Therefore, we also analysed the
      impact of having a private practice on a physician's intention to change sector.
      We found that private practice had a positive, statistically significant effect
      on the intention to switch sector in 1998 and 2003. Results also suggest that job
      satisfaction decreases a physician's intention to switch sector, although for
      1998 it had no effect. Surprisingly, job dissatisfaction significantly increased
      the physicians' intentions to leave the public sector only in the 1988 data.

PMID- 17188395
TI  - Fighting fly genes.
AB  - Fighting by organisms such as mice and Drosophila provides model systems for
      investigating the genetic basis of aggression. Recent experiments to dissect male
      aggressive behaviour in Drosophila melanogaster, using gene expression analysis
      of selected lines followed by mutant analysis, have identified new candidate
      genes associated with male aggression, including one strong candidate that
      encodes a cytochrome P450 enzyme. Here, we describe the study of aggressive
      behaviour in flies and explore the possibility that cytochrome P450 is involved
      in aggression.

PMID- 17188396
TI  - Cytoplasmic male sterility: a window to the world of plant mitochondrial-nuclear
      interactions.
AB  - Mitochondrial function depends on the coordinate action of nuclear and
      mitochondrial genomes. The genetic dissection of these interactions presents
      special challenges in obligate aerobes, because the viability of these organisms
      depends on mitochondrial respiration. The plant trait cytoplasmic male sterility
      (CMS) is determined by the mitochondrial genome and is associated with a pollen
      sterility phenotype that can be suppressed or counteracted by nuclear genes known
      as restorer-of-fertility genes. Here, I review the nature and the origin of the
      genes that determine CMS, together with recent investigations that have exploited
      CMS to provide new insights into plant mitochondrial-nuclear communication. These
      studies have implicated mitochondrial signaling pathways, including those
      involved in regulating cell death and nuclear gene expression, in the elaboration
      of CMS. The molecular cloning of nuclear genes that restore fertility (i.e.
      restorer-of-fertility genes) has identified genes encoding pentatricopeptide
      repeat proteins as key regulators of plant mitochondrial gene expression.

PMID- 17188397
TI  - Chromatin structure in the genomics era.
AB  - The packaging of eukaryotic genomes into chromatin has a large influence on DNA
      templated processes, such as transcription. The availability of genome sequences
      and 'genomics' technologies such as DNA microarrays and high-throughput
      sequencing had an immediate effect on the study of transcriptional regulation, by
      enabling researchers to identify the coregulation patterns of thousands of genes.
      These same resources are now being used successfully to study the structure of
      chromatin. Here, I review some of these new genomics approaches to understanding
      chromatin structure in eukaryotes.

PMID- 17188398
TI  - Heterosis: revisiting the magic.
AB  - Heterosis results in the phenotypic superiority of a hybrid over its parents with
      respect to traits such as growth rate, reproductive success and yield. This
      hybrid vigor is determined by non-mutually exclusive mechanisms, including
      dominance complementation, overdominance and epistasis. Heterotic genes
      responsible for elevating crop yields are now being sought using genomics,
      particularly transcriptomics, but with contradictory results. Because heterosis
      is an environmentally modified quantitative phenotype, genomic analyses alone
      will not suffice. Future research should focus on integrating genomic tools in a
      framework of comprehensive quantitative trait locus (QTL)-based phenotyping,
      followed by map-based cloning. This 'phenomics' approach should identify loci
      controlling heterotic phenotypes, and improve understanding of the role of
      heterosis in evolution and the domestication of crop plants.

PMID- 17188400
TI  - Expectancies, dietary restraint, and test meal intake among undergraduate women.
AB  - This study investigated the relationship between self-reported dietary restraint
      and expectancies about caloric content on test meal consumption among
      undergraduate women. Participants completed two test meal sessions during which
      they were asked to consume as much milkshake from a covered opaque container as
      they wished. In one session, participants were instructed that the milkshake was
      made with high-calorie ingredients, and in the other that the milkshake was made
      with low-calorie ingredients. The milkshakes in both sessions were actually made
      with the same ingredients. Participants' mean consumption was less on the low
      calorie instruction day (402 g) than on the high-calorie instruction day (382 g),
      but the difference was not statistically significant. In addition, few
      significant relationships were observed between dietary restraint measures and
      total intake on either the low- or high-calorie instruction days. Thus, this
      study supports a growing body of literature indicating that scores on measures of
      dietary restraint are not related to the actual restriction of food intake.

PMID- 17188401
TI  - Antibodies against a multiple-peptide conjugate comprising chemically modified
      human immunodeficiency virus type-1 functional Tat peptides inhibit infection.
AB  - We demonstrated recently that selective side-chain modification of functional
      cysteine-rich (Tat(21-40)) and arginine-rich (Tat(53-68)) domains of the HIV-1
      Tat protein blocks pathogenic activities of these peptides while retaining their
      immunological characteristics. In the present study, we have synthesized a
      multiple-peptide conjugate system comprising modified Tat(21-40) and Tat(53-68)
      peptides (HIV-1-Tat-MPC). Immunization of mice with this highly homogeneous 10.7
      kDa HIV-1-Tat-MPC synthetic construct induced an effective immune response in
      mice. The antibodies generated against HIV-1-Tat-MPC efficiently suppressed Tat
      induced viral replication and significantly reduced HIV-associated cytopathic
      effects in human monocytes. These results indicate that epitope-specific
      antibodies directed against functional sites of Tat protein using non-pathogenic
      peptides inhibit HIV pathogenesis. The HIV-1-Tat-MPC, therefore, has potential
      for the development of a safe, effective, and economical therapeutic vaccine to
      reduce the progression of HIV infection.

PMID- 17188399
TI  - Breast cancer detection by Michaelis-Menten constants via linear programming.
AB  - The Michaelis-Menten constants (K(m) and V(max)) operated by linear programming,
      were employed for detection of breast cancer. The rate of enzymatic hydrolysis of
      fluorescein diacetate (FDA) in living peripheral blood mononuclear cells (PBMC),
      derived from healthy subjects and breast cancer (BC) patients, was assessed by
      measuring the fluorescence intensity (FI) in individual cells under incubation
      with either the mitogen phytohemagglutinin (PHA) or with tumor tissue, as
      compared to control. The suggested model diagnoses three conditions: (1) the
      subject is diseased, (2) the diagnosis is uncertain, and (3) the subject is not
      diseased. Out of 50 subjects tested, 44 were diagnosed correctly, in 5 cases the
      diagnosis was not certain, and 1 subject was diagnosed incorrectly.

PMID- 17188402
TI  - Synthesis and antiviral activity of C-fluoro-branched cyclopropyl nucleosides.
AB  - A series of novel fluorocyclopropyl nucleosides were synthesized starting from
      acetol using the Simmons-Smith reaction as a key reaction. All the nucleosides
      synthesized were assayed against several viruses. Among the compounds
      synthesized, the uracil analogue 22 showed moderate anti-HCMV activity (10.61
      microg/mL, in AD-169).

PMID- 17188403
TI  - [Attitudes towards immunization].
AB  - PURPOSE: Ever since vaccination was introduced, a minority has been opposed to
      this practice. Recently however, fear of adverse events and a general questioning
      of the usefulness of certain vaccines have led to wariness on the part of the
      broader public. In France, this phenomenon is particularly striking since the
      hepatitis B vaccination campaign. We wished to analyse the situation by drawing
      on the results of surveys conducted by the French Institute of Prevention and
      Health Education (Institut national de prevention et d'education pour la sante,
      INPES) which sought to gain a better understanding of health care professionals'
      and the general public's attitudes towards immunization. MAIN POINTS: Although
      the majority of French men and women are convinced of the overall benefit of
      vaccination in the past, they increasingly question vaccine safety and usefulness
      today. PERSPECTIVES: In order to prevent further deterioration of the situation,
      efforts must be made to enhance public and professional awareness as to the
      stakes involved in the control of vaccine preventable diseases.

PMID- 17188404
TI  - [Painful thoracic neuropathy disclosing Sjogren's syndrome: first report].
AB  - INTRODUCTION: Thoracic neuropathy is rare, and is usually associated with
      diabetes mellitus. We report a first case of isolated multi-metameric thoracic
      neuropathy revealing Sjogren's disease. EXEGESIS: A 64-year old man consulted for
      symptoms suggesting a progressive and extensive (from T7 to T10) bilateral
      thoracic neuropathy. Diabetes mellitus and other causes of neuropathy were
      excluded. Spinal MRI, electromyography and CSF analysis were normal. Though the
      patient had no sicca syndrome symptoms, the diagnosis of Sjogren's syndrome was
      made on hypergammaglobulinemia, elevated ACAN (1/5000) with anti-SSA specificity
      and a grade III minor salivary gland biopsy. He improved spectacularly on
      corticosteroids (prednisone, 1 mg/kg/d). Sicca syndrome became clinically evident
      in April 2006. CONCLUSION: Pure sensitive thoracic neuropathy can reveal
      Sjogren's syndrome.

PMID- 17188406
TI  - Peacocks and Jellyfish: steps and strategies for successful conference chairing.

PMID- 17188405
TI  - [Rituximab induced remission of pemphigus vulgaris: 2 cases].
AB  - INTRODUCTION: Pemphigus vulgaris frequently requires corticoids and immuno
      suppressive drugs. The disease and the side effects of the drugs severely affect
      the quality of life, and sometime the vital prognosis of the patients. Other
      treatments than corticosteroids and immunosuppressive drugs are needed. EXEGESIS:
      We report 2 additional cases of pemphigus vulgaris uncontrolled by corticoids and
      immuno-suppressive drugs that responded spectacularly to rituximab. One patient
      had a recently onset disease, that was active despite 1,5 mg/kg/day prednisone
      and 1,5 g/day mycophenolate. She had a complete remission during 15 months after
      rituximab treatment. At relapse, another rituximab cycle led to a prompt
      remission. The other patient had longstanding pemphigus vulgaris complicated by
      cutaneous infections on prednisone (20 mg/d), immunosuppressive drugs and
      intravenous immune globulins. She had a prompt and complete remission after
      rituximab. CONCLUSION: Rituximab seems to be a promising drug for refractory
      pemphigus vulgaris. The benefit to risk ratio of this drug in this new indication
      must be precisely documented.

PMID- 17188408
TI  - Lateral dermoid cyst.
AB  - This is an unusual case of a lateral dermoid cyst that caused some diagnostic
      confusion.

PMID- 17188407
TI  - Biomechanical study of prophylactic internal fixation of the radial
      osteocutaneous donor site using the sheep tibia model.
AB  - This study investigated the strengthening effect of different types of plate and
      position after osteotomy of the sheep tibia, which is a model for the radial
      osteocutaneous donor site. Fifty matched pairs of adult sheep tibias were tested
      in torsion and four-point bending. Firstly, the weakening effect of an osteotomy
      was compared with the intact bone. Then pairs of bones with an osteotomy were
      compared with and without reinforcement with different types of 3.5mm plate. The
      plate was placed in either the anterior (over the defect) or posterior (on the
      intact cortex) position. In torsion the mean strength of the intact bone was 45%
      greater than after osteotomy (P=0.02). The reinforced bone was on average 61%
      stronger than the unreinforced bone (P<0.001). In bending the mean strength of
      the intact bone was 188% greater than after osteotomy (P=0.02). The reinforced
      bone was on average 184% stronger then the unreinforced bone (P<0.001). The tibia
      was able to withstand much greater loads in bending. The dynamic compression
      plate was the strongest reinforcement in both torsion and bending. The position
      of the plate did not alter the strengthening effect in torsion but the posterior
      position resisted greater bending loads (P=0.01). This may not be relevant in
      clinical practice as the radius is likely to fracture first as a result of lower
      torsional forces.

PMID- 17188409
TI  - Routine antibiotic prophylaxis is not necessary during operations to remove third
      molars.
AB  - The purpose of this study was to evaluate the efficacy of antibiotic prophylaxis
      during removal of impacted third molars. We studied 150 patients with impacted
      mandibular or maxillary third molars who were divided randomly into three groups.
      The first was given amoxicillin 2g combined with clavulanic acid, orally daily
      for 5 days postoperatively; starting at the end of the operation. The second
      group was given the same drugs but the regimen started 5 days before the
      operation. The third was given no antibiotics. Pain, infection, swelling,
      alveolar osteitis, and interincisal mouth opening (mm) were evaluated. There were
      no significant differences among the groups in the incidence of these
      complications. We cannot recommend routine oral antibiotic prophylaxis in third
      molar surgery.

PMID- 17188410
TI  - Chemical behavior of residential lead in urban yards in the United States.
AB  - Long after federal regulations banned the use of lead-based paints and leaded
      gasoline, residential lead remains a persistent challenge. Soil lead is a
      significant contributor to this hazard and an improved understanding of
      physicochemical properties is likely to be useful for in situ abatement
      techniques such as phytoremediation and chemical stabilization. A laboratory
      characterization of high-lead soils collected from across the United States shows
      that the lead contaminants were concentrating in the silt and clay fractions, in
      the form of discrete particles of lead, as observed by scanning electron
      microscopy coupled with energy dispersive X-ray analysis. Soil lead varied widely
      in its solubility behavior as assessed by sequential and chelate extractions.
      Because site-specific factors (e.g., soil pH, texture, etc.) are believed to
      govern the solubility of the lead, understanding the variability in these
      characteristics at each site is necessary to optimize in situ remediation or
      abatement of these soils.

PMID- 17188411
TI  - Culture and stigma: adding moral experience to stigma theory.
AB  - Definitions and theoretical models of the stigma construct have gradually
      progressed from an individualistic focus towards an emphasis on stigma's social
      aspects. Building on other theorists' notions of stigma as a social,
      interpretive, or cultural process, this paper introduces the notion of stigma as
      an essentially moral issue in which stigmatized conditions threaten what is at
      stake for sufferers. The concept of moral experience, or what is most at stake
      for actors in a local social world, provides a new interpretive lens by which to
      understand the behaviors of both the stigmatized and stigmatizers, for it allows
      an examination of both as living with regard to what really matters and what is
      threatened. We hypothesize that stigma exerts its core effects by threatening the
      loss or diminution of what is most at stake, or by actually diminishing or
      destroying that lived value. We utilize two case examples of stigma--mental
      illness in China and first-onset schizophrenia patients in the United States--to
      illustrate this concept. We further utilize the Chinese example of 'face' to
      illustrate stigma as having dimensions that are moral-somatic (where values are
      linked to physical experiences) and moral-emotional (values are linked to
      emotional states). After reviewing literature on how existing stigma theory has
      led to a predominance of research assessing the individual, we conclude by
      outlining how the concept of moral experience may inform future stigma
      measurement. We propose that by identifying how stigma is a moral experience, new
      targets can be created for anti-stigma intervention programs and their
      evaluation. Further, we recommend the use of transactional methodologies and
      multiple perspectives and methods to more fully capture the interpersonal core of
      stigma as framed by theories of moral experience.

PMID- 17188412
TI  - Pragmatic pluralism: mutual tolerance of contested understandings between
      orthodox and alternative practitioners in autologous stem cell transplantation.
AB  - High-dose chemotherapy and autologous stem cell transplantation (ASCT) is used to
      treat some advanced malignancies. It is a traumatic procedure, with a high
      complication rate and significant mortality. ASCT patients and their carers draw
      on many sources of information as they seek to understand the procedure and its
      consequences. Some seek information from beyond orthodox medicine. Alternative
      beliefs and practices may conflict with conventional understanding of the theory
      and practice of ASCT, and 'contested understandings' might interfere with patient
      adherence to the strict and demanding protocols required for successful ASCT. The
      present study, conducted in Sydney, Australia, examines narrative-style
      interviews with 10 sequentially recruited ASCT patients and nine of their carers
      conducted at the time of transplant and three months later. Transcripts were read
      for instances of mention of alternative advice, and for instances of contested
      understanding of information relevant to the transplant. Patients and carer pairs
      expressed closely concordant views about alternative advice. Five pairs were
      consulting alternative practitioners. Contested understanding was expressed in
      four domains--understandings of the transplant itself and its underlying theory,
      of the relationship between the components of the 'transplant', of the nature and
      role of stem cells, and of beliefs about bodily function and life-style.
      Contested understandings of the transplant treatment were expressed as
      predominantly personal interpretations of orthodox information. Patients and
      carers seemed to recognise that alternative and conventional systems were
      discordant, yet they were able to separate the two, and adhere to each practice
      without prejudicing their medical treatment. A single case of late, post
      transplant repudiation of Western medicine is discussed to emphasise some of the
      possible determinants of dissonance when it does occur.

PMID- 17188413
TI  - Psychosis in a patient with Fabry's disease and treatment with aripiprazole.

PMID- 17188414
TI  - Hepatoprotection of tea seed oil (Camellia oleifera Abel.) against CCl4-induced
      oxidative damage in rats.
AB  - The oil of tea seed (Camellia oleifera Abel.) is used extensively in China for
      cooking. This study was designed to evaluate the effects of tea seed oil on
      CCl(4)-induced acute hepatotoxicity in rats. Male SD rats (200+/-10 g) were pre
      treated with tea seed oil (50, 100, and 150 g/kg diet) for six weeks before
      treatment with a single dose of CCl(4) (50% CCl(4), 2 mL/kg of bw,
      intraperitoneally), the rats were sacrificed 24h later, and blood samples were
      collected for assaying serum biochemical parameters. The livers were excised for
      evaluating peroxidation products and antioxidant substances, as well as the
      activities of antioxidant enzymes. Pathological histology was also performed. The
      results showed that a tea seed oil diet significantly (p<0.05) lowered the serum
      levels of hepatic enzyme markers (alanine aminotransferase, aspartate
      aminotransferase, and lactate dehydrogenase), inhibited fatty degeneration,
      reduced the content of the peroxidation product malondialdehyde, and elevated the
      content of GSH. Pre-treatment of animals with tea seed oil (150 g/kg diet) could
      increase the activities of glutathione peroxidase, glutathione reductase and
      glutathione S transferase in liver when compared with CCl(4)-treated group
      (p<0.05). Therefore, the results of this study show that a tea seed oil diet can
      be proposed to protect the liver against CCl(4)-induced oxidative damage in rats,
      and the hepatoprotective effect might be correlated with its antioxidant and free
      radical scavenger effects.

PMID- 17188416
TI  - Ellagic acid, a natural polyphenol protects rat peripheral blood lymphocytes
      against nicotine-induced cellular and DNA damage in vitro: with the comparison of
      N-acetylcysteine.
AB  - The present work is aimed at evaluating the protective effect of ellagic acid
      (EA), a natural polyphenolic compound that is widely distributed in fruits and
      nuts against nicotine-induced toxicity in rat peripheral blood lymphocytes. The
      effect of EA against nicotine toxicity was compared with N-acetylcysteine (NAC),
      a well-known antioxidant. Lymphocytes were exposed to nicotine at the doses of
      0.125, 0.25, 0.5, 1, 2, 3 and 4 mM for 1h in culture media. Thiobarbituric acid
      reactive substances (TBARS), a lipid peroxidative marker and reduced glutathione
      (GSH), as indicative of endogenous antioxidant status were analyzed to fix the
      optimum dose. The lowest concentration eliciting significant damage was 1 mM
      nicotine and maximum damage was observed with 3 mM concentration, as evidenced by
      increased levels of TBARS and decreased levels of GSH. Hence, the test
      concentration was fixed at 3 mM nicotine. To establish most effective protective
      support we used five different concentrations of EA (10, 50, 100, 150 and 300
      microM) against 3 mM nicotine. A dose-dependent inhibitory effect was observed
      with all doses of EA. Maximum protection was observed at the dose of 100 microM
      EA. So, 100 microM dose was used for further studies. We have tested five
      different concentrations of NAC-0.25, 0.5, 1, 2 and 4 mM to elucidate the optimum
      protective dose against nicotine toxicity. One millimolar NAC showed a
      significant protection against nicotine toxicity. Protective effect of EA against
      nicotine toxicity was elucidated by analyzing the lipid peroxidative index, viz.,
      TBARS, hydroperoxides (HP) and endogenous antioxidant status, viz., superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced
      glutathione (GSH), Vitamins A, E and C. DNA damage and repair were assessed by
      using alkaline single-cell microgel electrophoresis (Comet assay) and
      micronucleus assay. There was a significant increase in the levels of lipid
      peroxidative index, severity in DNA damage and micronuclei number in nicotine
      treated group, which was positively modulated by EA treatment. Antioxidant status
      was significantly depleted in nicotine-treated group, which was effectively
      restored by EA treatment. The protection of EA against nicotine toxicity was
      equally effective to that of NAC. EA and NAC treatment alone did not produce any
      damage to the normal lymphocytes at their effective doses. These findings suggest
      the potential use and benefit of EA as a modifier of nicotine-induced
      genotoxicity.

PMID- 17188415
TI  - Preventive effect of naringin on cardiac markers, electrocardiographic patterns
      and lysosomal hydrolases in normal and isoproterenol-induced myocardial
      infarction in Wistar rats.
AB  - Diets rich in natural antioxidants are associated with reduced risk of heart
      diseases. This study was aimed to evaluate the preventive role of naringin on
      cardiac troponin T (cTnT), lactate dehydrogenase (LDH)-isoenzyme, cardiac marker
      enzymes, electrocardiographic (ECG)-patterns and lysosomal enzymes in
      isoproterenol (ISO)-induced myocardial infarction (MI) in male Wistar rats. Rats
      subcutaneously injected with ISO (85mg/kg) at an interval of 24h for 2 days
      showed a significant increase in the levels of cTnT, intensity of the bands of
      LDH-isoenzyme (LDH1 and LDH2) and the activities of cardiac marker enzymes such
      as creatine kinase-MB (CK-MB), creatine kinase (CK), LDH, aspartate transaminase
      (AST) and alanine transaminase (ALT) in serum with subsequent decrease in the
      activities of CK, LDH, AST and ALT in the heart and alterations in ECG-patterns.
      The activities of lysosomal enzymes (beta-glucuronidase, beta-N-acetyl
      glucosaminidase, beta-galactosidase, cathepsin-B and cathepsin-D) were increased
      significantly in serum and the heart of ISO-induced rats, but the activities of
      beta-glucuronidase and cathepsin-D were decreased significantly in the lysosomal
      fraction of the heart. Pretreatment with naringin (10, 20 or 40mg/kg) daily for a
      period of 56 days positively altered the levels of cTnT, intensity of the bands
      of the LDH1 and LDH2-isoenzyme and the activities of cardiac marker enzymes, ECG
      patterns and lysosomal hydrolases in ISO-induced rats. Thus, naringin possess
      cardioprotective effect in ISO-induced MI in rats.

PMID- 17188417
TI  - Retention of skills in medical students following minimal theoretical
      instructions on semi and fully automated external defibrillators.
AB  - AIM OF THE STUDY: There is consent that the use of automated external
      defibrillators (AED) by laypersons improves survival rates in case of cardiac
      arrest, but no evident consensus exists on the content and duration of training
      for this purpose. Acceptance of the implementation of Public Access
      Defibrillation programmes will depend on practical and target-oriented training
      concepts. The aim of this prospective randomised interventional study was to
      evaluate long-term effects of a specific, minimal training programme on using
      semiautomatic and fully automatic AEDs in simulated cardiac arrest. MATERIALS AND
      METHODS: In a mock cardiac arrest scenario 59 medical students with no specific
      previous medical education were tested during their first semester at medical
      school. Students who passed any medical emergency training were excluded. The
      subjects were evaluated before and after attending specified instructions of 15
      min duration and after a period of 6 months. Main end points were time to first
      shock, electrode-positioning and safety throughout the procedure. RESULTS: Mean
      time to first shock without prior instructions was 77.7+/-17.05 s. After
      instruction there was a significant improvement to 56.5+/-9.5 s (p<or=0.01) and
      after 6 months this time had only slightly elongated (59.9+/-8.9 s; p<or=0.01).
      Initially, correct electrode placement was observed in 84.4%. No difference was
      found immediately and 6 months after instructions (93.2% and 98.3%). All
      individuals performed safely. CONCLUSION: First year medical students with
      minimal instruction are able to use semiautomatic as well as fully automatic AED
      sufficiently fast and safe without prior training. A significant improvement in
      time to first shock can be detected up to 6 months after receiving non-specific
      instructions of 15 min duration.

PMID- 17188418
TI  - Synthesis and hydrolysis of pppGpp in mycobacteria: a ligand mediated
      conformational switch in Rel.
AB  - Bacteria respond to starvation by synthesizing a polyphosphate derivative of
      guanosine, (p)ppGpp, that helps the bacteria in surviving during stress. The
      protein in Gram-positive organisms required for (p)ppGpp synthesis is Rel, a
      bifunctional enzyme that carries out both synthesis and hydrolysis of this
      molecule. Rel shows increased pppGpp synthesis in the presence of uncharged tRNA,
      the effect of which is regulated by the C-terminal of Rel. We show by
      fluorescence resonance energy transfer that the distance between the N-terminus
      cysteine residue at the catalytic domain and C692 at the C-terminus increases
      upon the addition of uncharged tRNA. In apparent anomaly, the steady state
      anisotropy of the Rel protein decreases upon tRNA binding suggesting "compact
      conformation" vis-a-vis "open conformation" of the free Rel. We propose that the
      interaction between C692 and the residues present in the pppGpp synthesis site
      results in the regulated activity and this interaction is abrogated upon addition
      of uncharged tRNA. We also report here the binding of pppGpp to the C-terminal
      part of the protein that leads to more unfolding in this region.

PMID- 17188420
TI  - Merits of ozonation and catalytic ozonation pre-treatment in the algal treatment
      of pulp and paper mill effluents.
AB  - Since the performance of algal treatment for pulp mill effluent decreases with
      increasing color intensity and AOX content, which mainly originate from the
      chlorine bleaching of Kraft pulp, the separated CEH bleaching effluent was pre
      treated by both the conventional and the heterogeneous catalytic ozonation
      processes. An increase in the BOD(5)/COD ratio from 0.11 to 0.28 and 87% color
      abatement in terms of Pt-Co were achieved by catalytic ozonation, which had the
      best treatment performance. Biodegradability enhancement of the CEH effluent
      correlated well with a decrease in toxicity, high-molecular-weight-compound
      content, and AOX abatement. By the pre-treatment of the CEH bleaching effluent,
      the overall efficiencies of algal treatment of the combined pulp mill effluent in
      terms of the fractional removal of COD and color were increased from 76% and 53%
      to 86-90% and 96-99%, respectively. Effects of both the conventional and the
      catalytic ozonation pre-treatments on subsequent biological treatment were close
      to each other and they reduced the filling period of the Sequential Batch Reactor
      (SBR) cycle from 8 to 5 days.

PMID- 17188419
TI  - Assessing the potential of native tree species for carbon sequestration forestry
      in Northeast China.
AB  - Although the native forests of China are exceptionally diverse, only a small
      number of tree species have been widely utilized in forest plantations and
      reforestation efforts. We used dendrochronological sampling methods to assess the
      potential growth and carbon sequestration of native tree species in Jilin
      Province, Northeast China. Trees were sampled in and near the Changbaishan
      Biosphere Reserve, with samples encompassing old-growth, disturbed forest, and
      plantations. To approximate conditions for planted trees, sampling focused on
      trees with exposed crowns (dominant and co-dominant individuals). A log-linear
      relationship was found between diameter increment and tree diameter, with a
      linear decrease in increment with increasing local basal area; no significant
      differences in these patterns between plantations and natural stands were
      detected for two commonly planted species (Pinus koraiensis and Larix olgensis).
      A growth model that incorporates observed feedbacks with individual tree size and
      local basal area (in conjunction with allometric models for tree biomass), was
      used to project stand-level biomass increment. Predicted growth trajectories were
      then linked to the carbon process model InTEC to provide estimates of carbon
      sequestration potential. Results indicate substantial differences among species,
      and suggest that certain native hardwoods (in particular Fraxinus mandshurica and
      Phellodendron amurense), have high potential for use in carbon forestry
      applications. Increased use of native hardwoods in carbon forestry in China is
      likely to have additional benefits in terms of economic diversification and
      enhanced provision of "ecosystem services", including biodiversity protection.

PMID- 17188422
TI  - High-resolution multiple-unit EEG in cat auditory cortex reveals large spatio
      temporal stochastic interactions.
AB  - It has been argued that information processing in the cortex is optimised with
      regard to certain information theoretic principles. We have, for instance,
      recently shown that spike-timing dependent plasticity can improve an information
      theoretic measure called spatio-temporal stochastic interaction which captures
      how strongly a set of neurons cooperates in space and time. Systems with high
      stochastic interaction reveal Poisson spike trains but nonetheless occupy only a
      strongly reduced area in their global phase space, they reveal repetiting but
      complex global activation patterns, and they can be interpreted as computational
      systems operating on selected sets of collective patterns or "global states" in a
      rule-like manner. In the present work we investigate stochastic interaction in
      high-resolution EEG-data from cat auditory cortex. Using Kohonen maps to reduce
      the high-dimensional dynamics of the system, we are able to detect repetiting
      system states and estimate the stochastic interaction in the data, which turns
      out to be fairly high. This suggests an organised cooperation in the underlying
      neural networks which cause the data and may reflect generic intrinsic
      computational capabilities of the cortex.

PMID- 17188423
TI  - Transient bifurcations in neural error correction.
AB  - This paper presents an investigation into the responses of neurons to errors in
      presynaptic spike trains. Errors are viewed, in nonlinear dynamical terms, as
      brief-duration changes in stationary presynaptic spike trains which induce
      transient responses in the postsynaptic cell. As these are generally large
      magnitude transients, linearized neural models are not helpful. Instead, the
      responses of a full, nonlinear physiological model of a neuron that includes the
      recognized living prototype of an inhibitory synapse are analyzed. More
      specifically, the transients are examined in the context of the stationary
      behaviors that precede and succeed each error. It is shown that one and two
      dimensional bifurcation diagrams can be constructed from the transient responses-
      that there are marked changes in the transient responses at points that
      correspond to bifurcations in the stationary responses, qualitative changes in
      transients on either side of bifurcations, and only quantitative changes in
      transients between bifurcations.

PMID- 17188425
TI  - Hepatitis B virus integration, fragile sites, and hepatocarcinogenesis.
AB  - Chronic liver disease associated with long term hepatitis B virus (HBV) infection
      contributes importantly to the development of hepatocellular carcinoma (HCC). A
      salient feature of these chronic infections is the integration of subgenomic HBV
      DNA fragments into many different locations within the host DNA, suggesting that
      integration is random. Although this may promote genetic instability during liver
      regeneration which accompanies a bout of chronic liver disease, the actual role
      of integrated HBV DNA in hepatocarcinogenesis is uncertain. Importantly, most
      integration events retain the HBV open reading frame encoding the HBx antigen
      (HBxAg), which is the virus contribution to HCC. In addition, many integration
      events reported in the literature occur near or within fragile sites or other
      cancer associated regions of the human genome that are prone to instability in
      tumor development and progression. Genetic instability associated with
      integration potentially alters the expression of oncogenes, tumor suppressor
      genes, and microRNAs (miRNAs) that may contribute importantly to tumorigenesis.
      If so, then selected integration events may alter pathways that are rate limiting
      in hepatocarcinogenesis, thereby providing targets with diagnostic/prognostic
      potential and for therapeutic intervention.

PMID- 17188426
TI  - Clinical significance of serum angiocidin levels in hepatocellular carcinoma.
AB  - Angiocidin, a tumor-secreted protein, was measured in serum of 27 healthy
      volunteers and 33 hepatocellular carcinoma (HCC) patients. Healthy controls
      either hepatitis B surface antigen (HBsAg) positive or negative showed
      undetectable levels. Patients had levels of angiocidin ranging from 15.09 to
      195.73 pg/ml. Patients with stages III-IV had higher levels of angiocidin (97+/
      13 pg/ml, n=17) compared to those with stages I-II (63+/-37 pg/ml, n=16),
      p<0.043. Patients with microsatellite tumor nodules had higher average levels
      (98+/-55 pg/ml, n=17) compared to those without microsatellite nodules (51+/-27
      pg/ml, n=20), p<0.032. Our studies suggest that angiocidin predicts advanced
      stage and intra-hepatic metastasis.

PMID- 17188424
TI  - Role of Annexin-II in GI cancers: interaction with gastrins/progastrins.
AB  - The role of the gastrin peptide hormones (G17, G34) and their precursors
      (progastrins, PG; gly-extended gastrin, G-gly), in gastrointestinal (GI) cancers
      has been extensively reviewed in recent years [W. Rengifo-Cam, P. Singh, Role of
      progastrins and gastrins and their receptors in GI and pancreatic cancers:
      targets for treatment, Curr. Pharm. Des. 10 (19) (2004) 2345-2358; M. Dufresne,
      C. Seva, D. Fourmy, Cholecystokinin and gastrin receptors, Physiol. Rev. 86 (3)
      (2006) 805-847; A. Ferrand, T.C. Wang, Gastrin and cancer: a review, Cancer Lett.
      238 (1) (2006) 15-29]. A possible important role of progastrin peptides in colon
      carcinogenesis has become evident from experiments with transgenic mouse models
      [W. Rengifo-Cam, P. Singh, (2004); A. Ferrand, T.C. Wang, (2006)]. It is now
      known that growth stimulatory and co-carcinogenic effects of gastrin/PG peptides
      are mediated by both proliferative and anti-apoptotic effects of the peptides on
      target cells [H. Wu, G.N. Rao, B. Dai, P. Singh, Autocrine gastrins in colon
      cancer cells Up-regulate cytochrome c oxidase Vb and down-regulate efflux of
      cytochrome c and activation of caspase-3, J. Biol. Chem. 275 (42) (2000) 32491
      32498; H. Wu, A. Owlia, P. Singh, Precursor peptide progastrin(1-80) reduces
      apoptosis of intestinal epithelial cells and upregulates cytochrome c oxidase Vb
      levels and synthesis of ATP, Am. J. Physiol. Gastrointest. Liver Physiol. 285 (6)
      (2003) G1097-G1110]. Several receptor subtypes have been described that mediate
      growth effects of gastrin peptides [W. Rengifo-Cam, P. Singh (2004); M. Dufresne,
      C. Seva, D. Fourmy, (2006)]. Recently, we identified Annexin II as a high
      affinity binding protein for gastrin/PG peptides [P. Singh, H. Wu, C. Clark, A.
      Owlia, Annexin II binds progastrin and gastrin-like peptides, and mediates growth
      factor effects of autocrine and exogenous gastrins on colon cancer and intestinal
      epithelial cells, Oncogene (2006), doi:10.1038/sj.onc.1209798]. Importantly, the
      expression of Annexin II was required for mediating growth stimulatory effects of
      gastrin and PG peptides on intestinal epithelial and colon cancer cells [P.
      Singh, H. Wu, C. Clark, A. Owlia, Annexin II binds progastrin and gastrin-like
      peptides, and mediates growth factor effects of autocrine and exogenous gastrins
      on colon cancer and intestinal epithelial cells, Oncogene (2006),
      doi:10.1038/sj.onc.1209798], suggesting that Annexin-II may represent the elusive
      novel receptor for gastrin/PG peptides. The importance of this finding in
      relation to the structure and function of Annexin-II, especially in GI cancers,
      is described below. Since this surprising finding represents a new front in our
      understanding of the mechanisms involved in mediating growth effects of
      gastrin/PG peptides in GI cancers, our current understanding of the role of
      Annexin-II in proliferation and metastasis of cancer cells is additionally
      reviewed.

PMID- 17188428
TI  - Fusion genes in angiomatoid fibrous histiocytoma.
AB  - Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of low
      malignant potential and uncertain differentiation. Only three genetically
      investigated cases of AFH have been reported. Two of them displayed a FUS-ATF1
      fusion gene and one showed an EWSR1-ATF1 chimera. Using RT-PCR analysis, we have
      identified the EWSR1-ATF1 fusion transcript, and delineated the genomic
      breakpoints, in two new cases of AFH. Previously, the EWSR1-ATF1 fusion protein
      has been suggested to activate expression of the MITF-M transcript, and therefore
      the expression pattern of the MITF gene was studied. The MITF-M transcript was
      not detected in either AFH, in line with the finding that the co-activator SOX10
      was not expressed. Thus, of the five AFH that have been molecularly analyzed to
      date, two have displayed a FUS-ATF1 fusion gene and three have shown an EWSR1
      ATF1 chimera. There is no apparent correlation between the type of fusion gene
      and clinicopathologic features. Nonetheless, RT-PCR for these fusion transcripts
      remains a valuable diagnostic adjunct in the distinction between AFH and other
      soft tissue tumors or metastases that may simulate it.

PMID- 17188429
TI  - Microwave assisted rapid and complete degradation of atrazine using TiO(2)
      nanotube photocatalyst suspensions.
AB  - A technology, microwave-assisted photocatalysis on TiO(2) nanotubes, which can be
      applied to degrade atrazine rapidly and completely, was investigated. TiO(2)
      nanotubes were prepared, and confirmed by XRD, TEM and ESR. Microwave-assisted
      photocatalytic degradation of atrazine in aqueous solution was investigated. The
      result indicates that atrazine is completely degraded in 5min and the
      mineralization efficiency is 98.5% in 20min, which is obviously more efficient
      than that by the traditional photocatalytic degradation methods. It may be
      attributed to the intense UV radiation generated by electrodeless discharge lamps
      under microwave irradiation, the increased number of OH, additional defect sites
      on TiO(2) under the irradiation of microwave and larger specific surface area of
      TiO(2) nanotubes which could adsorb more organic substances to degrade than
      TiO(2) nanoparticles. Along with the degradation of atrazine, the concentrations
      of Cl(-) and NO(3)(-) increase gradually. In 20min [Cl(-)] and [NO(3)(-)] are 3,
      27.8mg/L, respectively, which are close to their stoichiometric values. The major
      intermediates of atrazine were identified by HPLC/MS and possible degradation
      pathways of atrazine in microwave-assisted photocatalysis on TiO(2) nanotubes
      were proposed.

PMID- 17188427
TI  - Tumor-suppressive activity of retinoic acid receptor-beta in cancer.
AB  - Retinoids, a group of structural and functional analogs of vitamin A, are known
      to regulate a large number of essential biological processes and to suppress
      carcinogenesis. The effects of retinoids are mainly mediated by nuclear retinoid
      receptors, which include retinoic acid receptors (RARs) and retinoid X receptors
      (RXRs). Each receptor has three subtypes (alpha, beta, and gamma) and each
      subtype has different isoforms. Retinoic acid receptor-beta (RAR-beta) has four
      isoforms that have different affinities to retinoids and different biological
      functions. Loss of expression of RAR-beta(2) during cancer development is
      associated with tumorigenesis and retinoid resistance; induction of its
      expression, on the other hand, can suppress carcinogenesis. Expression of another
      isoform, RAR-beta(4), is increased in various types of cancer. RAR-beta(4)
      transgenic mice develop hyperplasia and neoplasia in various tissues, and
      induction of RAR-beta(4) expression increases the growth of tumor cells that do
      not express RAR-beta(2). Future studies will focus on molecular pathways
      involving RAR-beta(2) and the role of RAR-beta(4) in cancer development.

PMID- 17188430
TI  - Experimental study on a low-temperature SCR catalyst based on MnO(x)/TiO(2)
      prepared by sol-gel method.
AB  - A catalyst based on MnO(x)/TiO(2) was prepared by sol-gel method for low
      temperature selective catalytic reduction (SCR) of NO with NH(3). Focusing on the
      effects of the operating parameters, the SCR reaction was investigated at
      temperatures from 353 to 523K under steady and transient states. Under the
      optimal conditions, the efficiency of NO removal could exceed 90% at temperature
      of 423K. Furthermore, within the range investigated, the reaction order of NO,
      NH(3), O(2) was determined to be 1, 0, and 0.5, respectively. Apparent activation
      energy was also calculated to be 38kJ/mol, lower than that for most of the
      catalysts reported by previous investigations.

PMID- 17188431
TI  - Identification and biochemical analysis of a mitochondrial endonuclease of
      Podospora anserina related to curved-DNA binding proteins.
AB  - We purified and characterized previously from Podospora anserina mitochondria an
      endonuclease, active on single-stranded, double-stranded and flap DNA, with RNAse
      H activity, named P49 according to the major 49 kDa band observed on SDS-PAGE.
      Edman sequencing allowed us to identify the corresponding gene called nuc49. Here
      we report the properties of the (His)-tagged NUC49 protein expressed in E. coli.
      We show that this protein does exhibit an endonuclease activity on plasmid DNA,
      circular recessed and flap M13 substrate with short protruding single strand.
      However, in contrast to the mt endonuclease purified fraction it does not present
      RNase H activity and does not cleave linear flap substrate. The activity
      differences between the protein expressed in E. coli and the mitochondrial
      endonuclease fraction previously described are discussed. NUC49 presents a strong
      homology with the S. pombe CDB4 curved DNA binding protein which belongs to a
      large family including the human cell cycle protein PA2G4 and is able to bind
      curved DNA. The results constitute the first description of a mitochondrial
      endonuclease activity associated to this family of proliferation associated
      homologous proteins. The function of this endonuclease either in recombination,
      repair or mt DNA rearrangements remains to be determined.

PMID- 17188432
TI  - The relationship between depressed mood, self-efficacy and affective states
      during the drinking driving sequence.
AB  - Relationships between depressed mood, abstinence confidence and temptation, and
      experienced emotions just before and during recent drinking driving sequences
      (drinking driving emotional states: DDES) were examined in a sample of DUI
      (Driving Under the Influence) offenders. Depressed mood offenders (41% of sample)
      reported lower abstinence confidence, higher temptation, and higher DDES,
      especially in association with negative affective states. Implications for
      interventions with depressed mood DUI offenders are discussed.

PMID- 17188433
TI  - Radiation-induced production of PAR-1 and TGF-beta 1 mRNA in lung of C57Bl6 and
      C3H murine strains and influence of pharmacoprophylaxis by ACE inhibitors.
AB  - Transforming growth factor beta 1 (TGF-beta1) plays an important role in the
      development of radiation- and drug-induced organ diseases. Proteinases-activated
      receptor 1 (PAR-1) is involved in many pathophysiologic processes after its
      activation by serine proteases. The aim of the present study was to determine
      messenger RNA (mRNA) production of TGF-beta1 and PAR-1 in the lungs after local
      irradiation. Mice of C57BL/6 and C3H/J strains with different susceptibility to
      fibrosis development were exposed to a of 15Gy. Non-irradiated mice of both
      strains were used as negative controls. Control (irradiated) and irradiated
      angiotensin-converting enzyme (ACE) inhibitor-treated animals were examined
      simultaneously. The ACE inhibitor group was given butylaminiperindopril for 9
      days after irradiation (15Gy) at a daily dose of 0.1 or 0.2mg/kg per rectum. On
      day 9, all mice were sacrificed, and the production of mRNA TGF-beta1 and PAR-1
      in lung tissue was determined semiquantitatively using reverse transcriptase
      polymerase chain reaction, and immunohistochemical analysis of PAR-1 expression
      in pulmonary tissue was performed. In the fibrosing murine strain C57Bl/6, there
      was an increase in the mRNA TGF-beta1 and PAR-1 levels in lungs 9 days after
      irradiation as compared with non-irradiated controls and non-fibrosing murine
      strain C3H/J. In butylaminiperindopril-treated mice, a decrease in transcript of
      TGF-beta1 and PAR-1 was observed. Thus, PAR-1 is involved in radiation-induced
      lung fibrosis in correlation with TGF-beta1 production. Administration of ACEI
      influences PAR-1 and TGF-beta1 expression.

PMID- 17188434
TI  - Calretinin: an immunohistochemical marker for the normal functional endometrial
      stroma and alterations of the immunoreactivity in dysfunctional uterine bleeding.
AB  - Calretinin has been identified in the central nervous system, in various
      endocrine and mesothelial cells, and is often used as an immunohistochemical tool
      in the pathologic diagnosis. We have recently observed its presence in the
      endometrial stromal cells (ESC) of the normal functionalis (FL). Endometrial
      tissue from various physiologic and pathologic conditions was submitted for
      immunostaining for calretinin. For each condition, two to ten samples were
      tested. Calretinin displayed a strong cytoplasmic and occasionally nuclear
      reactivity for ESC of the normal FL in all physiologic phases of the normal
      menstrual cycle except for the breakdown period. Reactivity was limited in the
      superficial zone of the FL in proliferative phase, and was extensive in all
      stages of secretory phase. The ESC of the basilis layer, postmenopausal women,
      endometriotic and adenomyotic tissue, endometrial polyps, hyperplasia, carcinoma,
      and ESC neoplasms were not reactive for the marker. In endometrial specimens from
      patients with dysfunctional bleeding, there were varying degrees of decrease in
      reactivity in a patchy pattern. We demonstrated for the first time that
      calretinin reactivity of the ESC is strong and diffuse in a zonal pattern in the
      normal FL of the normal cycling endometrium. In endometrium with dysfunctional
      bleeding, postmenopausal, ectopic, hyperplastic, and neoplastic endometria, the
      ESC displayed focally decreased to negative reactivity. Calretinin can be used as
      a marker for normally functional ESC. Further study is necessary to investigate
      the mechanism and the role that calretinin plays in the physiologic cyclic
      changes of the endometrium.

PMID- 17188435
TI  - Se18.9, an anti-phagocytic factor H binding protein of Streptococcus equi.
AB  - Evasion of phagocytosis is an important virulence determinant of Streptococcus
      equi (S. equi subsp. equi), the cause of equine strangles and distinguishes it
      from the closely related but much less virulent S. zooepidemicus (S. equi subsp.
      zooepidemicus). We describe Se18.9, a novel H factor binding protein secreted by
      S. equi but not by S. zooepidemicus that reduces deposition of C3 on the
      bacterial surface and significantly reduces the bactericidal activity of equine
      neutrophils suspended in normal serum for both S. equi and S. zooepidemicus.
      Se18.9 is secreted abundantly by actively dividing cells and is also bound to the
      bacterial surface. Strong serum and mucosal antibody responses are elicited in S.
      equi infected horses. Although a gene identical to se18.9 was not detected in S.
      zooepidemicus, sequences encoding proteins of similar size with similar signal
      peptide sequences were found in 3 of 12 randomly selected strains. Since Se18.9
      is unique to S. equi, and immunoreactive with convalescent sera and mucosal IgA,
      it has potential for immunodiagnosis and for study of mucosal antibody response
      to S. equi.

PMID- 17188436
TI  - Spermatogenesis in testis xenografts grafted from pre-pubertal Holstein bulls is
      re-established by stem cell or early spermatogonia.
AB  - Xenografting of testis explants into recipient mice has resulted in successful
      restoration of spermatogenesis in several species. Most studies have utilized
      neonatal donor tissue, although a few have used prepubertal testes. In Holstein
      bulls, prepubertal development of the testis occurs between 16 and 32 weeks of
      age. The purpose of the present study was to determine the optimal age during
      prepubertal development of Holstein bulls for testis grafting. Explants of testis
      tissue from Holstein bulls between 12 and 32 weeks of age (2 bulls/age; 6 ages)
      were subcutaneously grafted into castrated or intact immunocompromised mice
      (n=8/age), then recovered after 75 and 173 days (n=4 mice/grafting period) and
      evaluated histologically for spermatogenic progression. Seminiferous tubules were
      assigned a score based on the most advanced type of germ cell present within the
      tubule and the average for all tubules scored (n=25) within an explant was
      calculated. Scores for all explants per mouse (n=6) were averaged to give a
      single spermatogenic progression score per mouse. No difference in spermatogenic
      progression of grafts between intact and castrated recipients was observed.
      Spermatocytes were observed in testis grafts from bulls of all ages 75 days post
      grafting. At 173 days, the spermatogenic progression score for explants derived
      from 20 weeks bulls was greater than all ages except 12 weeks donors (p<0.05),
      with 8% of tubules containing spermatids. Donor material from bulls older than 20
      weeks had lesser spermatogenic progression scores largely attributed to the
      greater number of atrophic tubules in grafts from older donors. Grafts from 28
      and 32 weeks donors showed signs of degeneration by 75 days post-grafting, with
      30 and 55% atrophic tubules, respectively, and lesser spermatogenic efficiency
      scores. By 173 days post-grafting, 72% of tubules in explants from 32 weeks
      donors were atrophic. The results of the present study suggest that the early
      stages of prepubertal development are optimal for testis grafting while advanced
      spermatogenesis in the donor tissue prior to grafting had a negative effect on
      graft development. Spermatogenesis within the grafts apparently needs to be re
      established by spermatogonial stem cells or early spermatogonia.

PMID- 17188437
TI  - Clinical, ultrasonographic and pathological features following unilateral
      vasectomy in rams.
AB  - The effects of vasectomy on testes and related structures of animal species and
      men are largely disputable. These possible effects were studied in the ram, an
      established experimental animal model used to investigate genitalia
      pathophysiology. In each of five rams, vasectomy in the left spermatic cord was
      carried out; subsequently, the clinical and ultrasonographic features were
      monitored up to 12 months post-operatively. The rams were sequentially
      euthanatized 1, 3, 6, 9 and 12 months post-operatively; gross- and histo
      pathological examination of their testes and related structures were carried out.
      Four of the five rams developed sperm granulomas at the proximal to the testis
      end of vas deferens or/and at the tail of the epididymis; these were palpable
      from the first and the third month after vasectomy, respectively.
      Ultrasonographic findings on the vasectomy side were increased size and
      echogenicity of the epididymal tail, as well as anechoic areas, representing
      sperm granulomas, visible in the epididymal tail 1 week after vasectomy and in
      the proximal to the testis end of vas deferens 4 weeks after vasectomy. Gross
      pathological findings were limited on the vasectomy side and included adhesions
      between the parietal and the visceral vaginal tunic, enlarged and firm epididymal
      tail and presence of sperm granulomas at the epididymal tail or/and at the
      proximal to the testis end of vas deferens; the granulomas contained creamy
      material. Histopathological changes were observed mainly in the epididymal tails,
      consisting of a central mass of spermatozoa, surrounded by a layer of
      macrophages, surrounded in turn by loose vascular connective tissue rich in
      lymphocytes and plasma cells. With the exception of signs of mild
      hypospermatogenesis observed in one ram euthanatized 9 months after surgery, and
      of a slight increase in seminiferous tubule diameter and in seminiferous
      epithelium height in the rams euthanatized 6 and 9 months after surgery, which
      are both findings of no clinical importance, no clinical, ultrasonographic, gross
      or other histo-pathological changes were observed in the testicular parenchyma
      during a 12-month post-operative period. These results demonstrate that vasectomy
      has little if any detrimental effect on the morphologic characteristics of the
      spermatogenesis in rams.

PMID- 17188438
TI  - Evaluation of three equine FSH superovulation protocols in mares.
AB  - Superovulation could potentially increase embryo recovery for immediate transfer
      or cryopreservation. The objectives were to evaluate the effect of pretreatment
      with progesterone and estradiol (P+E) on follicular response to eFSH and compare
      doses of eFSH and ovulatory agents on follicular development and ovulation in
      mares. In Experiment 1, 40 mares were assigned to one of four treatment groups.
      Group 1 consisted of untreated controls. Group 2 mares were administered eFSH
      without pretreatment with P+E. Group 3 mares were administered P+E for 10 days
      starting in mid-diestrus followed by eFSH therapy. Group 4 mares were
      administered P+E for 10 days followed by eFSH therapy. All treated mares were
      administered 12.5mg eFSH twice daily and prostaglandins were given on the second
      day of eFSH therapy. Mares were bred with fresh semen the day of hCG
      administration and with cooled semen the following day. The numbers of
      preovulatory follicles and ovulations were lower for mares treated with P+E prior
      to eFSH treatment. Pretreatment with P+E in estrus also resulted in a lower
      embryo recovery rate per ovulation compared to the other two eFSH treatment
      groups. In Experiment 2, two doses of eFSH (12.5 and 6.25mg) and two ovulation
      inducing agents (hCG and deslorelin) were evaluated. The number of preovulatory
      follicles was greater for mares given 12.5mg of eFSH compared to mares given
      6.25mg. Number of ovulations was greatest for mares given 12.5mg of eFSH twice
      daily followed by administration of hCG. Embryo recovery per flush was similar
      among treatment groups, but the percent of embryos per ovulation was higher for
      mares given the low dose of eFSH. In summary, there was no advantage to giving
      P+E prior to eFSH treatment. In addition, even though the lower dose of eFSH
      resulted in fewer ovulations, embryo recovery per flush and embryo recovery per
      ovulation were similar or better for those given the lower dose of eFSH.

PMID- 17188439
TI  - In vitro evaluation of dendrimer prodrugs for oral drug delivery.
AB  - Dendrimer-based prodrugs were used to enhance the transepithelial permeability of
      naproxen, a low solubility model drug. The stability of the dendrimer-naproxen
      link was assessed. Naproxen was conjugated to G0 polyamidoamine (PAMAM)
      dendrimers either by an amide bond or an ester bond. The stability of G0 prodrugs
      was evaluated in 80% human plasma and 50% rat liver homogenate. The cytotoxicity
      of conjugates towards Caco-2 cells was determined and the transport of the
      conjugates across Caco-2 monolayers (37 degrees C) was reported. In addition, one
      lauroyl chain (L) was attached to the surface group of G0 PAMAM dendrimer of the
      diethylene glycol ester conjugate (G0-deg-NAP) to enhance permeability. The
      lactic ester conjugate, G0-lact-NAP, hydrolyzed slowly in 80% human plasma and in
      50% rat liver homogenate (t(1/2)=180 min). G0-deg-NAP was hydrolyzed more rapidly
      in 80% human plasma (t(1/2)=51 min) and was rapidly cleaved in 50% liver
      homogenate (t(1/2)=4.7 min). The conjugates were non-toxic when exposed to Caco-2
      cells for 3h. Permeability studies showed a significant enhancement in the
      transport of naproxen when conjugated to dendrimers; L-G0-deg-NAP yielding the
      highest permeability. Dendrimer-based prodrugs with appropriate linkers have
      potential as carriers for the oral delivery of low solubility drugs such as
      naproxen.

PMID- 17188440
TI  - Tourette's syndrome with cervical disc herniation.
AB  - Tourette's syndrome is manifested in a broad spectrum of motor, vocal, and
      behavioral disturbances. Movement disorders, such as tics, may contribute to the
      development of cervical myelopathy owing to the effects of involuntary movements
      on the neck. However, the association of cervical myelopathy with motor tics of
      the head and neck is rare. We report here a case of a violent, repetitive neck
      extension due to Tourette's syndrome that developed cervical myelopathy caused by
      cervical disc herniation.

PMID- 17188441
TI  - P2X7-induced apoptosis decreases by aging in mice myeloblasts.
AB  - In the current study, the ability of ATP to promote apoptosis in myeloblasts at
      different ages was investigated. We have observed that high concentration of
      extracellular ATP (>1mM), which activates P2X(7) receptor, produced cell
      shrinkage an increase in the number of events in the sub-G(0)/G(1) region of the
      cellular cycle and annexin-V/propidium iodide label, which characterizes the
      apoptotic cell death. In addition, BzATP produced apoptosis, but not ADP and UTP.
      Gr-1(+) cells express the P2X(7) receptor and oxidized ATP, a specific P2X(7)
      inhibitor, blocked the ATP-dependent apoptosis. ATP-dependent apoptosis is
      decreased by aging in myeloblasts of 12 and 22-month-old mice. Furthermore,
      P2X(7) expression decrease was observed in older mice, explaining apoptosis
      decrease. This decrease in apoptosis by aging may be related to some diseases in
      the myelocyte lineage.

PMID- 17188442
TI  - Three faces of mortalin: a housekeeper, guardian and killer.
AB  - Mortalin was first cloned as a mortality factor that existed in the cytoplasmic
      fractions of normal, but not in immortal, mouse fibroblasts. A decade of efforts
      have expanded its persona from a house keeper protein involved in mitochondrial
      import, energy generation and chaperoning of misfolded proteins, to a guardian of
      stress that has multiple binding partners and to a killer protein that
      contributes to carcinogenesis on one hand and to old age disorders on the other.
      Being proved to be an attractive target for cancer therapy, it also warrants
      attention from the perspectives of management of old age diseases and healthy
      aging.

PMID- 17188443
TI  - Usage of the T1 effect of an iron oxide contrast agent in an animal model to
      quantify myocardial blood flow by MRI.
AB  - BACKGROUND: To present a new method for fully quantitative analysis of myocardial
      blood flow (MBF) using magnetic resonance imaging. The first pass of an
      intravascular iron oxide contrast medium can be used to quantify myocardial
      perfusion. The technique was validated in an animal model using colored
      microspheres. MATERIALS AND METHODS: In six pigs, a tracking catheter was
      positioned in the left anterior descending artery (LAD). Dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) was performed on a 1.5-T scanner
      using a hybrid gradient-echo/echoplanar imaging (GRE-EPI) sequence. Regional
      myocardial blood flow (rMBF) was altered by either inducing vasodilatation with
      adenosine or creating coronary artery obstruction. The T(1) effect of a
      superparamagnetic iron oxide-based contrast medium (Resovist) administered at a
      dose of 8 micromol/kg was used. Upslope, time-to-peak and peak intensity were
      calculated from the signal intensity-time curves and absolute rMBF using the Kety
      Schmidt equation; results were compared to those obtained using colored
      microspheres. RESULTS: The mean rMBF calculated by MRI was 1.49 (+/-6.91,
      quartile width) ml/min/g versus 3.21 (+/-1.61) ml/min/g measured by means of
      microspheres under resting conditions. rMBF increased to a mean of 6.21 (+/-2.83)
      ml/min/g versus 4.22 (+/-1.70) ml/min/g under adenosine and was reduced to zero
      flow in total occlusion. Linear regression showed the best correlation for
      upslope (R=0.714), time-to-peak (R=0.626) and the Kety-Schmidt equation
      (R=0.584). CONCLUSIONS: The T(1) effect of an iron oxide-based contrast medium
      allows determination of rMBF when using the Kety-Schmidt equation. The results
      are similar to those obtained with the standard of reference, colored
      micropheres, but not better than the results of the semiquantitative approach.

PMID- 17188445
TI  - Improved photostability indicating ion-pair chromatography method for pergolide
      analysis in tablets and in the presence of cyclodextrins.
AB  - Pergolide (PG) a semi-synthetic ergot alkaloid derivative used mainly for the
      treatment of Parkinson's disease is known to be a photosensitive drug substance.
      The major photodegradation products are PG sulphoxide (SX) and PG sulphone (SN),
      which are also the main impurities of the bulk drug substance. It is widely
      metabolized to more than 10 metabolites including SX and SN. In this work an
      improved photostability indicating ion-pair chromatography method for PG mesilate
      was developed. The method can be applied in the determination of PG and
      impurities in aqueous solutions and in tablets for routine analysis. This new
      method is appropriate for the quantitative determination of PG in the presence of
      its impurities and photodegradation products and can also be used for PG
      complexes with cyclodextrins (commonly used as photostabilizing agents).
      Furthermore it is suitable for the quantitation of its impurities and its thermal
      or photo-induced decomposition products. Separation was achieved on a ThermoQuest
      C(18) BDS column and Sodium octanosulphonate was used as ion-pairing agent.
      Analysis was performed at 223 nm. Validation parameters included: specificity,
      linearity, precision and accuracy, limit of quantitation and suitability. The
      method was found to be specific and linear for PG, as well as for SX and, SN
      impurities. The recovery was 100.83+/-0.46% for PG, 99.86+/-0.33% for SX and
      99.77+/-1.84% for SN. Finally the photodegradation profile of PG mesilate was
      studied in different initial sample concentration. The obtained result revealed
      that: PG photolysis is catalyzed by its degradation products and that decrease of
      initial sample concentration reduces the rate of PG photoinduced degradation.

PMID- 17188444
TI  - Role of diffusion weighted MR in the discrimination diagnosis of the cystic
      and/or necrotic head and neck lesions.
AB  - PURPOSE: The purpose was to determine whether the diffusion weighted imaging
      (DWI) was able to differentiate necrotic tumor or metastatic lesions from
      infected necrotic lesions such as abscesses and necrotic lymphadenitis in the
      neck. MATERIALS AND METHODS: DWI was performed on 37 consecutive patients with 85
      head and neck necrotic and cystic lesions. The lesions were classified into four
      categories: metastatic lymph node involvement including lymphoma, necrotic tumor,
      abscesses and necrotic lymphadenitis. Each lesion was histopathologically studied
      and proved. RESULTS: In 12 patients, there were 35 necrotic lymphadenitis
      (necrotic tuberculosis lymphadenitis, n=18; necrotic nonspecific suppurative
      lymphadenitis, n=17). Of the 15 necrotic metastatic nodes, 11 lesions were
      lymphomatous involvement and 4 lesions were other tumor involvement. Other 11
      patients have abscesses. Thirteen primary tumoral necrotic lesions arose in the
      neck of nine patients. All of the abscesses and necrotic lymphadenitis showed
      hyperintensity on DWI, in contrast to necrotic tumor and necrotic nodal
      metastasis that showed hypointensity on DWI. DWI successfully differentiated
      metastatic nodes and necrotic tumors from necrotic lymphadenitis and abscesses.
      CONCLUSION: DWI may be supportive for differentiating necrotic tumor lesions such
      as necrotic tumor and metastatic necrotic nodes from the infective necrotic
      lesions such as necrotic lymphadenitis and abscesses in the head and neck.

PMID- 17188446
TI  - Activity of sodium metabisulfite against planktonic and biofilm Staphylococcus
      species.
AB  - Biofilm-forming staphylococci cause a majority of intravascular catheter-related
      infections. We evaluated the effect of sodium metabisulfite, a preservative
      commonly added to intravenously administered pharmaceuticals as an antioxidant
      and previously used as a catheter lock solution, on planktonic and biofilm
      staphylococci at clinically encountered concentrations. Sodium metabisulfite
      exhibited bactericidal activity against planktonic Staphylococcus aureus,
      Staphylococcus lugdunensis, and Staphylococcus epidermidis at concentrations of
      512, 512, and 1024 microg/mL, respectively. A concentration of 720 microg/mL
      inhibited cell growth by all 3 species in a biofilm formation assay. However,
      established S. aureus and S. lugdunensis biofilms showed less than 1.5 log10
      decreases in viable cell counts when treated with 720 microg/mL of sodium
      metabisulfite for 24 h. These in vitro results suggest that the use of sodium
      metabisulfite as a catheter lock may inhibit staphylococcal colonization of
      catheters, thereby preventing catheter-related infection.

PMID- 17188447
TI  - Evaluation of a modified Taqman assay detecting pathogenic Leptospira spp.
      against culture and Leptospira-specific IgM enzyme-linked immunosorbent assay in
      a clinical environment.
AB  - A Taqman assay for the detection of pathogenic Leptospira was modified to suit
      the LightCycler instrument. The modified assay was found to have an analytical
      sensitivity of 10 copies/reaction. The assay was then compared to the current
      gold standard for acute phase detection, culture, and to a commercially available
      Leptospira-specific IgM enzyme-linked immunosorbent assay (ELISA). Of the 236
      samples including serum and ethylenediaminetetraacetic acid anticoagulated blood
      sample submitted for testing, polymerase chain reaction (PCR) was able to detect
      Leptospira DNA in 27 of the 28 culture positives and in 1 negative culture.
      Discrepant results were resolved by using the microscopic agglutination test on
      convalescent sera. The PCR was found to have a clinical specificity and
      sensitivity of 99.5% and 96.4%, respectively, when compared to the culture.
      Comparisons between culture and ELISA showed that the ELISA lack sensitivity
      (4.2%) and positive predictability (3.6%) for the detection of acute phase
      Leptospira infections. These results show that the modified LightCycler Taqman
      assay could be used as a replacement of culture for the detection of pathogenic
      Leptospira in a clinical setting.

PMID- 17188448
TI  - Granulicatella elegans native valve infective endocarditis: case report and
      review.
AB  - Granulicatella elegans is a fastidious organism that is rarely implicated as a
      cause of infective endocarditis. Here, we describe a patient with mitral valve
      prolapse who developed G. elegans endocarditis. The organism was isolated from
      blood cultures and the patient had mitral valvuloplasty and repair, and completed
      a course of 6 weeks of intravenous antibiotics with no sequela.

PMID- 17188449
TI  - In vitro postantibiotic effect of colistin on multidrug-resistant Acinetobacter
      baumannii.
AB  - Infections by multidrug-resistant Acinetobacter baumannii constitute an
      increasing threat for critically ill patients. Colistin is often the only
      antimicrobial retaining activity against these strains. The postantibiotic effect
      (PAE) of colistin was studied on 19 isolates of A. baumannii resistant to
      ampicillin/sulbactam, ciprofloxacin, and carbapenems with the viable count
      method. The mean PAEs of 1x MIC and 4x MIC concentrations of colistin on the
      tested isolates were 3.90 and 4.48 h, respectively, indicating that a modified
      dosage scheme with increased dosing intervals might retain activity whereas
      minimizing the incidence of adverse effects.

PMID- 17188450
TI  - A quick and cost-effective method for diagnosing disseminated histoplasmosis in
      children.
AB  - The examination of fecal mucus for detecting yeast cells of Histoplasma
      capsulatum has proved to be a useful tool for diagnosing disseminated
      histoplasmosis in paediatric patients in a study of 13 cases carried out in
      Ecuador.

PMID- 17188451
TI  - Chronic administration of methylphenidate activates mitochondrial respiratory
      chain in brain of young rats.
AB  - Methylphenidate is frequently prescribed for the treatment of attention
      deficit/hyperactivity disorder. Psychostimulants can cause long-lasting
      neurochemical and behavioral adaptations. The exact mechanisms underlying its
      therapeutic and adverse effects are still not well understood. In this context,
      it was previously demonstrated that methylphenidate altered brain metabolic
      activity, evaluated by glucose consumption. Most cell energy is obtained through
      oxidative phosphorylation, in the mitochondrial respiratory chain. Tissues with
      high energy demands, such as the brain, contain a large number of mitochondria.
      In this work, our aim was to measure the activities of mitochondrial respiratory
      chain complexes II and IV and succinate dehydrogenase in cerebellum, prefrontal
      cortex, hippocampus, striatum, and cerebral cortex of young rats (starting on
      25th post-natal day and finishing on 53rd post-natal day) chronically treated
      with methylphenidate. Our results showed that mitochondrial respiratory chain
      enzymes activities were increased by chronic administration of this drug.
      Succinate dehydrogenase was activated in cerebellum, prefrontal cortex and
      striatum, but did not change in hippocampus and brain cortex. Complex II activity
      was increased in cerebellum and prefrontal cortex and was not affected in
      hippocampus, striatum and brain cortex. Finally, complex IV activity was
      increased in cerebellum, hippocampus, striatum and brain cortex, and was not
      affected in prefrontal cortex. These findings suggest that chronic exposure to
      methylphenidate in young rats increases mitochondrial enzymes involved in brain
      metabolism. Further research is being carried out in order to better understand
      the effects of this drug on developing nervous system and the potential
      consequences in adulthood resulting from early-life drug exposure.

PMID- 17188452
TI  - Behavioral alterations induced by HgCl2 depend on the postnatal period of
      exposure.
AB  - This paper shows the toxicity of mercury (HgCl(2) 5mg/kg/day for 5 days, sc)
      applied at specific stages of development (1-5, 8-12 or 17-21 days old, 1st, 2nd
      and 3rd phases, respectively) on the performance of rats in three behavioral
      tasks and on cerebral mercury levels. The mercury exposure at the 1st and 2nd
      phases affected the performances of rats in the rim escape. Spontaneous
      alternation behavior was not altered by mercury exposure. In the open field task,
      habituation was absent when the rats were treated at the 1st phase, and the
      crossing response number was lower in rats exposed to mercury at the last period.
      In general, the brain accumulated large quantities of mercury. In short, the
      first days of postnatal life (1st phase) appeared to be more sensitive to mercury
      exposure than the other phases studied, since they presented behavioral deficits
      even at a time period somewhat after the exposure.

PMID- 17188453
TI  - The physician-patient working alliance.
AB  - OBJECTIVE: Cognitive and emotional dimensions of the physician-patient
      relationship (working alliance) were examined in relation to patients' beliefs
      about the usefulness of treatment (perceived utility), patients' beliefs about
      being able to adhere to treatment (adherence self-efficacy beliefs), patients'
      follow through on their treatment plan (adherence), and patients' satisfaction.
      METHODS: Participants were 51 men and 67 women who averaged 38.9 years of age
      (S.D.=12.28). Seventy-two were Euro-American, 23 African-American, 6 Asian
      American, 11 Hispanic, and 6 "Other." They reported an average of 7.3 years
      (S.D.=7.48) since being diagnosed with a chronic medical illness and an average
      of 7.1 (S.D.=4.88) visits to their doctor within the last year. Patients'
      conditions included HIV+/AIDS, hypertension, diabetes, asthma, and cancer.
      RESULTS: Results show moderate to strong relationships between working alliance
      and perceived utility (r=0.63, P<0.001), self-efficacy (r=0.47, P<0.001),
      adherence (r=0.53, P<0.001), and satisfaction (r=0.83, P<0.001). Regression
      analyses showed that ratings of the working alliance (SB=0.25, P<0.005) and self
      efficacy beliefs (SB=0.48, P<0.001) predicted patient adherence and that working
      alliance ratings (SB=0.83, P<0.001) also predicted patient satisfaction.
      CONCLUSION: The working alliance can be measured in medical care and appears to
      be strongly associated with patients' adherence to and satisfaction with
      treatment. PRACTICE IMPLICATIONS: The working alliance is important in medical
      treatment, as it is associated with patient adherence and satisfaction. Patients'
      self-efficacy ought to be assessed and promoted as it is also associated with
      treatment adherence.

PMID- 17188454
TI  - Treatment of tumour recurrence after resection of hepatocellular carcinoma.
      Analysis of 97 consecutive patients.
AB  - OBJECTIVE: To evaluate the long-term results of aggressive treatment of HCC
      recurrence. METHODS: Two hundred and nine consecutive patients underwent hepatic
      resection for HCC in our hospital. Tumour recurrence was diagnosed in 97 (51%) of
      the 190 patients with curative resection. Sixteen underwent hepatic resection:
      two right hepatectomies, one three-segmentectomy, one left hepatectomy, five two
      segmentectomies, six segmental resections and one subsegmentectomy. Two patients
      with metastasis in the spine were submitted to a vertebral body resection. Twenty
      five patients were treated with percutaneous ethanol injection or intra-arterial
      chemoembolization. Fifty-four patients with a poor performance status and liver
      function or multiple extra hepatic recurrences did not receive any treatment.
      RESULTS: There were no operative deaths. The postoperative mortality rate was
      5.5% (one patient). The cumulative overall survival after the second resection
      was respectively 89%, 46% and 31% at 1, 3 and 5 years. There was a significant
      difference in survival between patients treated with repeat resection and those
      submitted to a non-surgical or conservative treatment (p<0.0001). There were no
      differences in operative deaths, postoperative mortality and morbidity between
      the first and second hepatic resection. CONCLUSIONS: Aggressive management with
      combined resection or loco regional therapy for intrahepatic recurrence and
      resection of isolated extra-hepatic recurrence may offer long-term survival in
      selected patients. Second liver resection for recurrence of HCC can be safely
      performed.

PMID- 17188456
TI  - Gastrointestinal digestion of food allergens: effect on their allergenicity.
AB  - This paper reviews the in vitro digestion models developed to assess the
      stability digestion of food allergens, as well as the factors derived from the
      methodology and food structure that may affect the assay results. The adequacy of
      using the digestion stability of food allergens as a criterion for assessing
      potential allergenicity is also discussed. Data based on the traditional pepsin
      digestibility test in simulated gastric fluid are discussed in detail, with
      special attention to the influence of the pH and pepsin: allergen ratio in the
      pepsinolysis rate. This review points out the importance of using physiologically
      relevant in vitro digestion systems for evaluating digestibility of allergens.
      This would imply the sequential use of digestive enzymes in physiological
      concentrations, simulation of the stomach/small intestine environment (multi
      phase models) with addition of surfactants such as phospholipids or bile salts,
      as well as the consideration of the gastrointestinal transit and the effect of
      the food matrices on the allergen digestion and subsequent absorption through the
      intestinal mucosa. In vitro gastrointestinal digestion protocols should be
      preferably combined with immunological assays in order to elucidate the role of
      large digestion-resistant fragments and the influence of the food matrix on the
      stimulation of the immune system.

PMID- 17188455
TI  - [Coronary stents and anaesthesia: it is time to have national data].
AB  - We report 13 cases of coronary stent patients, undergoing a non cardiac surgery.
      Despite an heterogenous perioperative management of antiplatelet agents, none of
      these patients developed any significant complications. Recently, several case
      reports of postoperative drug eluting stent thrombosis have been reported.
      However, the actual incidence of this dramatic event is not known. This confirms
      the need to perform prospective studies or registries of patients with coronary
      stents undergoing non cardiac surgery, in order to propose evidence-based
      recommendations on perioperative antiplatelet management in such patients.

PMID- 17188457
TI  - Pneumonia in mice inoculated experimentally with Acanthamoeba polyphaga
      mimivirus.
AB  - In an attempt to elucidate whether Acanthamoeba polyphaga mimivirus (APM) was
      pathogenic (i.e., induces histological evidence of inflammation or tissue
      destruction or both) in mammalian host, we inoculated adult BALB/c (n=6) and
      C57BL/6 (n=6) mice with APM via intracardiac route. C57BL/6 mice developed
      histopathological features of pneumonia by post-inoculation day (PID) 3 and
      BALB/c mice, by PID7. The histopathological features of pneumonia, characterized
      by the presence of thickened alveolar walls with cellular infiltrates comprising
      mononuclear leukocytes, macrophages and lymphocytes, diffuse alveolar damages
      with the formation of hyaline membrane and erythrocytes in the alveolar lumen,
      were most marked by PID 7. We conclude that APM is pathogenic in mice in
      experimental conditions.

PMID- 17188458
TI  - Two-dimensional electrophoresis of protein from cultured postimplantation rat
      embryos for developmental toxicity studies.
AB  - A simple method for two-dimensional electrophoresis (2-DE) of rat embryonic
      protein was described. Rat embryos cultured for 24h from day 10.5 of gestation
      were used as protein samples. Protein samples were lysed in rehydration buffer
      and separated by isoelectric focusing with immobilized pH gradient for the first
      dimension and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for
      the second dimension. The use of the DeStreak Reagent as an antioxidant in the
      lysis buffer and electrode pads in the isoelectric focusing greatly improved the
      2-DE pattern. When an embryo was used as a protein sample, about 800 protein
      spots were detected by silver staining in a 2-DE gel of the standard format.
      Eighty-one protein spots were identified by mass spectrometry for a primary 2-DE
      map. The same method could be applied to yolk sac membranes from the cultured
      embryos. The present method was considered to be suitable for a concomitant 2-DE
      analysis in in vitro developmental toxicity studies.

PMID- 17188459
TI  - Evolutionary dynamics of the ABCA chromosome 17q24 cluster genes in vertebrates.
AB  - ABCA is a subfamily of ATP-binding-cassette (ABC) transporter genes. In this
      subfamily, it was found that five ABCA genes cluster in a head-to-tail pattern in
      the human and mouse genomes, but only one was found in fish. To understand better
      the evolution of this cluster of genes, we screened 11 vertebrate genome
      sequences and newly identified 28 ABCA cluster genes. Comparative genomic
      analysis reveals that the ABCA5 gene is relatively evolutionarily conserved. In
      contrast, the repertoires of the other ABCA genes in this cluster diverge
      tremendously among species, which is due mainly to postspeciation duplications.
      In addition, maximum likelihood analysis reveals that positive selection is
      acting on the paralogous genes ABCA6 and Abca8a, suggesting that these two genes
      have possibly acquired new functions after duplication. Because most eukaryotic
      ABC proteins integrate into the cytoplasmic membrane and transport a wide range
      of substrates across it, we conjecture that newly duplicated ABCA cluster genes
      are under diversifying selection for the ability to recognize a diverse array of
      substrates.

PMID- 17188460
TI  - A map of nuclear matrix attachment regions within the breast cancer loss-of
      heterozygosity region on human chromosome 16q22.1.
AB  - There is abundant evidence that the DNA in eukaryotic cells is organized into
      loop domains that represent basic structural and functional units of chromatin
      packaging. To explore the DNA domain organization of the breast cancer loss-of
      heterozygosity region on human chromosome 16q22.1, we have identified a
      significant portion of the scaffold/matrix attachment regions (S/MARs) within
      this region. Forty independent putative S/MAR elements were assigned within the
      16q22.1 locus. More than 90% of these S/MARs are AT rich, with GC contents as low
      as 27% in 2 cases. Thirty-nine (98%) of the S/MARs are located within genes and
      36 (90%) in gene introns, of which 15 are in first introns of different genes.
      The clear tendency of S/MARs from this region to be located within the introns
      suggests their regulatory role. The S/MAR resource constructed may contribute to
      an understanding of how the genes in the region are regulated and of how the
      structural architecture and functional organization of the DNA are related.

PMID- 17188461
TI  - Penile gangrene in a patient on renal dialysis: CT findings.
AB  - We presented a case of a 63-year-old man with type 2 diabetes mellitus and end
      stage renal disease on hemodialysis. Precontrast CT images showed atrophy of
      kidneys bilaterally and calcification of the abdominal aorta, small branches of
      bilateral renal arteries and small arteries of the pelvis, including the internal
      pudendal artery and penile artery. Postcontrast CT scans revealed a nonenhancing
      glans penis with a clear margin relative to normal tissue. The CT findings were
      compatible with gangrenous penis and were confirmed by surgery and histology.
      Findings of CT images can help urologists to decide the cutting margin in
      planning surgery.

PMID- 17188462
TI  - Multiplicity of the interactions of Wnt proteins and their receptors.
AB  - Wnts are secreted proteins that are essential for a wide array of developmental
      and physiological processes. They signal across the plasma membranes by
      interacting with serpentine receptors of the Frizzled (Fz) family and members of
      the low-density-lipoprotein receptor-related protein (LRP) family. Recent
      advances in the Wnt signaling field have revealed that Wnt-unrelated proteins
      activate or suppress Wnt signaling by binding to Fzs or LRP5/6 and that atypical
      receptor tyrosine kinases mediate Wnt signaling independently of Fz and/or
      function as a Fz co-receptor. This review highlights recent progress in our
      understanding of the multiplicity of Wnts and their receptors. We discuss how the
      interaction between the ligands and receptors activate distinct intracellular
      signaling pathways. We also discuss how intracellular trafficking of Wnt
      signaling components can regulate the sensitivity of cells to Wnts.

PMID- 17188463
TI  - Abnormal glucose metabolism in the anterior cingulate cortex in patients with
      schizophrenia.
AB  - Changes in glucose metabolism were studied in the brains of schizophrenic
      patients treated with neuroleptics, using [(18)F]fluoro-deoxy-glucose positron
      emission tomography (FDG-PET). Fourteen male and eight female patients in their
      thirties and forties were studied in a resting state. Data from FDG-PET were
      processed with an anatomic standardization method, three-dimensional stereotactic
      surface projections (3D-SSP), which provided relative glucose metabolic values
      that mitigated the contamination of brain atrophy. Z-score maps indicating
      metabolic differences between the patient and control groups were also acquired.
      Metabolic values in 19 regions were evaluated in the right and left hemispheres.
      Patients showed decreased values in the frontal cortex, primary sensory regions
      and anterior cingulate cortex, more in the rostral affective subdivision than the
      dorsal cognitive subdivision in both hemispheres, and increased metabolic values
      in left and right basal ganglia, left temporal and right medial parietal regions.
      Values were more decreased in both anterior cingulate regions, and more increased
      in the right thalamus in male than female patients, suggesting gender-related
      dysfunction in the anterior cingulate and thalamus in schizophrenia. FDG-PET
      demonstrated that schizophrenia may be a disorder with a dysfunction of fronto
      striatal-thalamic circuitry including the cingulate cortex.

PMID- 17188464
TI  - Brain activation patterns during a selective attention test--a functional MRI
      study in healthy volunteers and unmedicated patients during an acute episode of
      schizophrenia.
AB  - In a previous functional magnetic resonance imaging (fMRI) study of high
      functioning outpatients with remitted schizophrenia, we found increased activity
      compared with healthy subjects across multiple areas of the brain, including the
      dorsolateral frontal cortex and the anterior cingulate, during a modified Stroop
      task. The same fMRI procedure was used in this subsequent study to investigate
      eight unmedicated patients during an acute episode of schizophrenia and eight
      healthy control subjects. Patients showed a reduced activation in dorsolateral
      prefrontal, anterior cingulate and parietal regions and a higher activation in
      temporal regions and posterior cingulate compared to healthy controls. Healthy
      controls showed a trend towards higher accuracy in the modified Stroop task
      compared to schizophrenia patients. Treatment with second generation
      antipsychotics may improve executive performance in patients with schizophrenia
      and facilitate a normalization of functional hypofrontality after symptomatic
      improvement.

PMID- 17188465
TI  - Scaling procedures in colloidal electro-optics.
AB  - In a series of recent papers, we demonstrate the possibility to use the complete
      electro-optic saturation curves (or arbitrary part of them) to analyse the
      polarization mechanisms of charged colloidal particles. Scaling of the electro
      optic saturation curves by field intensity permits to find the frequency range in
      which the functional dependence of the effects, hence the orientation mechanism
      remains unchanged. Similar procedure can be applied to verify the changes of this
      dependence with variation of particle electric parameters. When different
      polarization mechanisms are involved the new scale helps their analysis. The aim
      of the present paper is to summarize the basic applications and advantages of the
      scaling method in the electro-optic investigation of charged colloids.

PMID- 17188466
TI  - The nature of "unusual" electro-optical transients observed for DNA.
AB  - Unusual electro-optical transients have been observed for many different polymers
      and colloidal systems. These effects provoked serious confusion, because a simple
      minded interpretation can be completely misleading. The case of double helical
      DNA is of particular interest, because DNA has been studied in more detail than
      other systems and because of its biological function. DNA is subject to bending,
      which implies a loss of symmetry. Due to its high charge density, non-symmetric
      conformations must have a non-symmetric distribution of charges leading to a
      torque of considerable magnitude in the presence of external electric fields. The
      dipole moment describing this torque must be calculated in a coordinate system
      with its origin at the center of diffusion. The resulting dipole values are in
      the range of thousands of Debye units. Because the new dipole type is analogous
      to but not identical with permanent dipoles, the notation "quasi-permanent"
      dipole is suggested. Application of this concept, using commonly accepted
      parameters for DNA and established procedures for calculation of electro-optical
      transients, leads to "unusual" transients. Thus, these transients must be
      expected from well-known parameters of DNA double helices. The influence of the
      quasi-permanent dipole moment may be amplified considerably by hydrodynamic
      coupling. This effect has been demonstrated for the case of smoothly bent rods.
      Both model calculations and experiments illustrate the danger of getting data
      that may be completely misleading. For example, depending on pulse amplitudes
      and/or pulse lengths, electro-optical decays may be accelerated artificially due
      to superposition of decay components with opposite amplitudes. Experiments show
      that unusual transients and apparent acceleration effects disappear, when high
      frequency sine pulses are used for the electro-optical analysis of DNA. Electro
      optical effects depend upon the internal dynamics of the object under
      investigation. In general, the dynamics of DNA bending was assumed to be fast
      compared to rotational diffusion. Because stacking rearrangements in single
      stranded nucleic acids are relatively slow and recently the dynamics of the B-A
      transition was observed in the time range >1 micros, it is likely that there are
      also relatively slow rearrangements between bending conformers. Bending
      transitions are expected to be relatively fast, when there are no activation
      barriers in the bending pathway, and may be slow, when activation barriers must
      be passed between bending conformers.

PMID- 17188467
TI  - The p53 network: p53 and its downstream genes.
AB  - The tumor-suppressor gene p53 and its downstream genes consist of a complicated
      gene network. p53 is a key molecular node in the network, which is activated in
      response to several cellular signals resulting in the maintenance of genetic
      stability. Several cellular signals may activate the p53 network. When the
      expression of P53 is elevated, P53-MDM2 module and the ubiquitin system can
      accurately regulate the expression level of P53. P53 can bind to specific DNA
      sequence, activate its downstream genes expression, and control cell-cycle
      arrest, DNA repair, and apoptosis. Elucidating the function of p53 gene network
      will help understand the interaction mechanisms of p53 and its downstream genes.

PMID- 17188468
TI  - Thermal response of a microgel system.
AB  - Recent experimental studies [Z. Wu, B. Zhou, Z.B. Hu, Phys. Rev. Lett. 90 (2003)
      048304] on an uncharged aqueous poly-N-isopropylacrylamide (PNIPAM) dispersion
      have shown that this microgel system is sensitive to temperature. This system was
      also experimentally found to be modeled quite well by microgel particles
      interacting via a hard-sphere repulsive plus an inverse power (temperature
      dependent) attractive potential. To understand theoretically this thermally
      responsive PNIPAM dispersion, we apply a novel approach [G.F. Wang, S.K. Lai,
      Phys. Rev. E 70 (2004) 051402] to calculate its thermodynamic phase diagram.
      Differing from the conventional method in which the boundaries of the coexisting
      phases are the ultimate target, the present work places emphasis on crosshatching
      colloidal domains which include the homogeneous phase (gas, liquid or solid), two
      coexisting phases and perhaps also multi-phases in coexistence. Strategically,
      this was done by treating the coexisting phases as one composite system whose
      Helmholtz free energy density is written as the sum of constituent free energy
      densities each of which is weighed by its respective volume proportion. We show
      here that by minimizing the composite system's free energy density the phase
      diagram domains can all be determined in addition to the phase boundaries
      customarily obtained by imposing the conditions of equal pressure and equal
      chemical potential. Also, we present the theoretically predicted phase diagram of
      PNIPAM dispersion and compare it with the one observed experimentally.

PMID- 17188469
TI  - Electrophoretic flow behaviour and mobility of colloidal fluids and crystals.
AB  - We report on measurements of the electrophoretic mobility mu of charged colloidal
      spheres in the deionized state, where the suspensions show fluid or crystalline
      order. In the fluid state, parabolic flow profiles are observed due to electro
      osmotic solvent flow. In the crystalline state, complex flow profiles occur due
      to additional crystal cohesion. The mobility mu then may inferred from the flow
      velocity averaged over the complete cell cross section as performed in our home
      built super-heterodyne Doppler velocimeter. For two particle species of 68 and
      122 nm diameter we measured mu as a function of particle concentration. Starting
      from a plateau value at low concentration, mu decreases approximately
      logarithmically with increased concentration. Interestingly, the decrease of mu
      is not affected by the phase transition, indicating that electro-kinetic
      properties may be viewed as single particle properties even in the case of
      structure formation. Moving further along this line of thought, we show that this
      behaviour may indeed be captured near quantitatively by an ad hoc combination of
      charge renormalization calculations and the Standard Electro-kinetic Model
      originally designed for isolated, non-interacting particles. From this
      coincidence, we may conclude that (i) counter-ion condensation behind the
      hydrodynamic slip plane is the dominant effect of finite particle concentrations
      and leads to a decrease of the effective particle charge and (ii) an increased
      colloid concentration can be understood in terms of an elevated total ion
      concentration and that (iii) it can thus be reduced to a modification of the
      screening parameter, such that the problem can be mapped onto a single particle
      theory for an infinite electrolyte.

PMID- 17188470
TI  - The influence of drug partition coefficient on follicular penetration: in vitro
      human skin studies.
AB  - The aim of this study was to employ the novel skin sandwich system in order to
      quantify the influence of the octanol-water partition coefficient on follicular
      drug absorption in human skin. To this end, seven different drugs - estradiol,
      corticosterone, hydrocortisone, aldosterone, cimetidine, deoxyadenosine and
      adenosine - exhibiting a wide range of log octanol-water partition coefficients
      (logK(o/w)) but relatively similar molecular weights were selected as candidate
      solutes. Application of the skin sandwich technique yielded an interesting
      relationship between % follicular contribution and logK(o/w). The follicular
      contribution to total flux was small (4 and 2%) for the two most lipophilic drugs
      but varied between 34 and 60% for the remaining drugs of intermediate and low
      logK(o/w) values. Lipophilicity seems to be an important modulator of drug
      absorption into follicular orifices only above a critical logK(o/w) threshold.
      Below this critical logK(o/w) value, lipophilicity does not apparently influence
      the follicular contribution in an obvious way and the process is probably
      governed by other molecular properties. Identification of these other active
      properties would require performing this kind of a study on a much larger set of
      candidate drugs.

PMID- 17188471
TI  - Rat epidermal keratinocyte organotypic culture (ROC) compared to human cadaver
      skin: the effect of skin permeation enhancers.
AB  - The objective of this study was to evaluate the response of the rat epidermal
      keratinocyte organotypic culture (ROC) to permeation enhancers, and to compare
      these responses to those in human cadaver skin. Different concentrations of two
      mixtures for enhancing permeation were investigated, sodium dodecyl
      sulfate:phenyl piperazine and methyl pyrrolidone:dodecyl pyridinium chloride,
      using skin impedance spectroscopy and two experimental compounds, the lipophilic
      corticosterone and the hydrophilic sucrose. The chemical irritation effects of
      the formulations were evaluated based on leakage of lactate dehydrogenase enzyme
      (LDH) and cellular morphological perturbation. This study provides evidence for
      direct correlations of permeation/permeation, impedance/impedance and
      permation/impedance between the culture model and human skin. The only exception
      was the enhancer induced permeation of sucrose which was 1-40-fold higher in ROC
      compared to human skin, reflecting the more disordered lipid organization in
      stratum corneum and consequently the greater number of polar pathways. LDH
      leakage and cellular morphology indicated that it was possible to differentiate
      between safe permeation enhancers from irritating agents. This is not only the
      first study to have compared the enhancer effects on a cultured skin model with
      human skin, but also it has demonstrated enhancer induced irritation using an
      artificial skin model.

PMID- 17188472
TI  - Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of
      new biological UV filter.
AB  - The majority of chemical solar filters are cytotoxic, particularly on sensitive
      ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV
      filter would be interesting in dermatology, but more especially in ophthalmology.
      In fact, light damage to the eye can be avoided thanks to a very efficient ocular
      antioxidant system; indeed, the chromophores absorb light and dissipate its
      energy. After middle age, a decrease in the production of antioxidants and
      antioxidative enzymes appears with accumulation of endogenous molecules that are
      phototoxic. UV radiations can induce reactive oxygen species formation, leading
      to various ocular diseases. Because most UV filters are cytotoxic for the eye, we
      investigated the anti-UV properties of Calophyllum inophyllum oil in order to
      propose it as a potential vehicle, free of toxicity, with a natural UV filter
      action in ophthalmic formulation. Calophyllum inophyllum oil, even at low
      concentration (1/10,000, v/v), exhibited significant UV absorption properties
      (maximum at 300nm) and was associated with an important sun protection factor (18
      22). Oil concentrations up to 1% were not cytotoxic on human conjunctival
      epithelial cells, and Calophyllum inophyllum oil appeared to act as a
      cytoprotective agent against oxidative stress and DNA damage (85% of the DNA
      damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did
      not induce in vivo ocular irritation (Draize test on New Zealand rabbits).
      Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective
      properties, and therefore might serve, for the first time, as a natural UV filter
      in ophthalmic preparations.

PMID- 17188473
TI  - A scintigraphic investigation of the disintegration behaviour of capsules in
      fasting subjects: a comparison of hypromellose capsules containing carrageenan as
      a gelling agent and standard gelatin capsules.
AB  - Two-piece hard shell capsules made from hypromellose (or hydroxypropyl
      methylcellulose, HPMC) have been proposed as an alternative to conventional
      gelatin capsules for oral drug delivery; however, little is known about their in
      vivo behaviour. The aim of this study was to compare the disintegration of HPMC
      and gelatin capsules in fasted human subjects using the technique of gamma
      scintigraphy. HPMC capsules containing carrageenan as a gelling agent (QUALI
      V(R), Qualicaps) and gelatin capsules (Qualicaps) of size 0 were filled with a
      lactose-based mixture. The capsules were separately radiolabelled with indium-111
      and technetium-99m. Both capsules were administered simultaneously with 180ml
      water to eight healthy male subjects following an overnight fast. Each volunteer
      was positioned in front of the gamma camera and sequential 60s images were
      acquired in a continuous manner for 30min. No differences in the oesophageal
      transit of the two types of capsules were noted, with the capsules arriving in
      the stomach in a matter of seconds. All the capsules disintegrated in the
      stomach. The mean (+/-S.D.) disintegration time for the HPMC capsules was 9+/
      2min (range 6-11min). The corresponding mean time for the gelatin capsules was
      7+/-4min (range 3-13min). These disintegration times were not significantly
      different (P=0.108, paired t-test). In conclusion, HPMC and gelatin capsules show
      rapid and comparable in vivo disintegration times in the fasted state. HPMC
      capsules containing carrageenan as a gelling agent therefore offer a practical
      alternative to gelatin capsules as an oral drug delivery carrier.

PMID- 17188474
TI  - [Alteration of bronchomotor tone after deep inhalation. Mechanisms and pediatric
      data].
AB  - There is significant alteration of airway calibre after deep inhalation (DI). An
      increase of airway calibre has been evidenced in children in case of mild
      asthmatic obstruction and after a positive response to methacholine or exercise
      challenge. Such an increase is blunted in the presence of a moderate to severe
      asthmatic airway obstruction and no bronchodilatory effect of DI has been found
      in infants. Bronchial hyperreactivity and airway inflammation strongly influence
      post-DI alterations of bronchomotor tone. Airways and lung parenchyma are
      interdependent but both exhibit imperfect elasticity. Hysterisis characterizes
      imperfect elasticity of pressure-volume relationship. The mechanical theory of
      relative hysteresis between airway and lung parenchyma is the main mechanism
      implicated in the induced changes of airway calibre. DI may influence results of
      lung function testing in children. The technique may be of interest to increase
      sensibility of routine lung function testing in children.

PMID- 17188475
TI  - [Bracelet localisation of chickenpox: a case of atypical varicella].
AB  - We report on a 3-year-old child with bracelet localisation of chickenpox.
      Varicella with unusual clinical aspects and course is known as atypical
      varicella; it is characterized by its unique clinical features, unusual
      distribution, or a prolonged course. In case of atypical varicella, clinical
      diagnosis can be difficult. Pre-existing factors have been reported such as
      immunocompromised status, sun exposition, local injury and pre-existing rash.

PMID- 17188476
TI  - A marine killer yeast against the pathogenic yeast strain in crab (Portunus
      trituberculatus) and an optimization of the toxin production.
AB  - A pathogenic yeast strain WCY which could cause milky disease in Portunus
      trituberculatus was identified to be Metschnikowia bicuspidate according to the
      results of routine yeast identification and 18S rDNA and ITS sequences. After
      screening of more than 300 yeast strains from different sources in marine
      environments, it was found that strain YF07b had the highest ability to produce
      killer toxin against the pathogenic yeast. Strain YF07b was identified to be
      Pichia anomala according to the results of routine yeast identification and 18S
      rDNA and ITS sequences. The optimal conditions for killer toxin production by
      strain YF07b were the production medium with 2.0% NaCl, pH 4.5, cultivation
      temperature of 20 degrees C and the optimal conditions for action of the crude
      killer toxin against the pathogenic yeast were the assay medium with 6.0% NaCl,
      pH 4.5 and temperature 15 degrees C.

PMID- 17188477
TI  - Fascinating metabolic pools of Pelargonium sidoides and Pelargonium reniforme,
      traditional and phytomedicinal sources of the herbal medicine Umckaloabo.
AB  - The metabolic pools of Pelargonium sidoides DC and Pelargonium reniforme CURT,
      associated with the origin of the herbal medicine Umckaloabo, exhibit remarkable
      diversity and complexity. They comprise a variety of phenolic and polyphenolic
      compounds, a notable wealth of highly oxygenated simple coumarins and a number of
      miscellaneous uncommon metabolites. Noteworthy, the roots of both species express
      conspicuously distinct coumarin variations that facilitate their identification.
      Of the range of coumarins identified the titled species shared the ubiquitous
      scopoletin and the unique members 6,7,8-trihydroxycoumarin and 8-hydroxy-5,6,7
      trimethoxycoumarin merely. Furthermore, the current data on the coumarin profiles
      suggest the occurrence of coumarin sulphates and coumarin glycosides to be
      apparently confined to P. sidoides, while the occurrence of conventional
      proanthocyanidins was a common chemical feature. An unprecedented diterpene,
      designated as reniformin, was encountered in the roots of P. reniforme,
      possessing a novel diterpene skeleton linked to a unique p-oxyphenethansulfonic
      moiety. Coumarins were less abundant in the aerial parts of both species. These
      were rich in flavonoids and hydrolysable tannins including a unique series of O
      galloyl-C-glucosylflavones (P. sidoides and P. reniforme) and novel ellagitannins
      with a (1)C(4) glucopyranose core in P. reniforme, trivially named pelargoniins,
      accompanied by the new 4-allyl-2,5-dimethoxyphenol-1-beta-D-glucoside. These
      Pelargoniums have thus represented an attractive source of fascinating secondary
      metabolites. A proprietary extract of the roots of P. sidoides, EPs 7630, has
      been developed from this traditional herbal medicine and introduced into modern
      phytotherapy in Europe. Structural examination of EPs 7630 constituents showed
      excellent agreement of the profile with that of P. sidoides.

PMID- 17188478
TI  - EPs 7630, an extract from Pelargonium sidoides roots inhibits adherence of
      Helicobacter pylori to gastric epithelial cells.
AB  - Helicobacter pylori specifically adheres to gastric host cells, mainly based on
      carbohydrate-mediated cell-cell interaction. The extract of Pelargonium sidoides
      roots (EPs) 7630), a South African herbal remedy, is currently used to treat
      acute bronchitis. EPs 7630 prevents bacteria from attaching to cell membranes.
      Therefore, the ability of EPs 7630 to interfere with H. pylori growth and
      adhesion to gastric epithelial cells (AGS cells) was tested in vitro. EPs 7630
      inhibited H. pylori growth and with higher potency adhesion to gastric AGS cells.
      EPs 7630 (50 and 100 microg/ml) reduced bacterial count attached to AGS cells by
      77% and 91%, respectively. The results suggest that the mode of action of EPs
      7630 is mainly related to its anti-adhesive activity.

PMID- 17188479
TI  - Treatment of rats with the Pelargonium sidoides extract EPs 7630 has no effect on
      blood coagulation parameters or on the pharmacokinetics of warfarin.
AB  - Umckaloabo is a herbal drug for the treatment of respiratory tract infections. It
      contains an aqueous ethanolic extract from roots of Pelargonium sidoides DC (EPs)
      7630) as the active ingredient. Polymeric polyphenols and coumarins have been
      identified as the principal ingredients of EPs 7630. In view of the coumarin
      content, it has been suggested that the administration of Umckaloabo could
      possibly be associated with an increased risk of bleeding. This study, therefore,
      investigated whether a change in blood coagulation parameters or an interaction
      with coumarin-type anticoagulants occurred after administration of EPs 7630 to
      rats. No effect on thromboplastin time (TPT), partial TPT (PTPT) or thrombin time
      (TT) was observed after oral administration of EPs 7630 (10, 75, 500 mg/kg) for 2
      weeks, while treatment with warfarin (0.05 mg/kg) for the same period resulted in
      significant changes in TPT and PTPT. If EPs 7630 (500 mg/kg) and warfarin (0.05
      mg/kg) were given concomitantly, the anticoagulant action of warfarin was not
      influenced. Similarly, the pharmacokinetics of warfarin were unchanged after pre
      treatment with EPs 7630 for 2 weeks. Coumarin-type anticoagulants inhibit the
      synthesis of vitamin K-dependent coagulation factors via an identical mechanism
      in rat and man, and have a similar pattern of metabolism in both species.
      Moreover, as the coumarins so far identified in EPs 7630 do not posses the
      structural characteristics needed for anticoagulant activity, it appears unlikely
      that an increased tendency to haemorrhage arises in patients after intake of
      Umckaloabo.

PMID- 17188480
TI  - In vitro evaluation of antibacterial and immunomodulatory activities of
      Pelargonium reniforme, Pelargonium sidoides and the related herbal drug
      preparation EPs 7630.
AB  - The importance of Pelargonium species, most notably Pelargonium reniforme and
      Pelargonium sidoides, in traditional medicine in the Southern African region is
      well documented. Nowadays, a modern aqueous-ethanolic formulation of the roots of
      P. sidoides (EPs) 7630) is successfully employed for the treatment of ear, nose
      and throat disorders as well as respiratory tract infections. To provide a
      scientific basis of its present utilization in phytomedicine, EPs 7630, extracts
      and isolated constituents of the titled Pelargoniums with emphasis on P. sidoides
      were evaluated for antibacterial activity and for their effects on nonspecific
      immune functions. The samples exhibited merely moderate direct antibacterial
      capabilities against a spectrum of Gram-positive and Gram-negative bacteria.
      Functional bioassays including an in vitro model for intracellular diseases, a
      fibroblast-lysis assay (tumour necrosis factor (TNF) activity), a fibroblast
      virus protection assay (IFN activity) and a biochemical assay for nitric oxides
      revealed significant immunomodulatory properties. Gene expression experiments
      (iNOS, IFN-alpha, IFN-gamma, TNF-alpha, Interleukin (IL)-1, IL-10, IL12, IL-18)
      not only confirmed functional data, they also clearly showed differences in the
      response of infected macrophages when compared to that of noninfected cells.
      ELISA confirmed the protein production of TNF-alpha, IL-1alpha and IL-12, while
      FACS analyses reaffirmed the cytokines IL-1alpha and IL-12 at the singular cell
      level. The current data provide convincing support for the improvement of immune
      functions at various levels, hence, validating the medicinal uses of EPs 7630.
      Despite considerable efforts, the remedial effects cannot yet be related to a
      chemically defined principle.

PMID- 17188482
TI  - Application of the "-Omic-" technologies in phytomedicine.
AB  - The proof of efficacy of phytopreparations and the determination of their mode of
      action are permanent challenges for an evidence-based phytotherapy. The
      technology platform of genomics, proteomics and metabolomics ("-omic-"
      technologies) are high-throughput technologies. They increase substantially the
      number of proteins/genes that can be detected simultaneously and have the
      potential to relate complex mixtures to complex effects in the form of
      gene/protein expression profiles. Provided that phytopreparation-specific
      signatures in the form of gene/protein expression profiles can be developed,
      these technologies will be useful for the chemical and pharmacological
      standardization and the proof of the toxicological potential of a plant extract.
      Over a long-term perspective they may economize the proof of efficacy, the
      determination of the mode of action of phytomedicines and allow to investigate
      herbal extracts without prominent active principle(s). The application of this
      genomics revealed already that gene expression profiles induced by single drugs
      and the ones induced by the combination of the same drugs can be entirely
      different. These results make the information of the mode of action of isolated
      "active principles/lead substances" of phytopreparations questionable. The
      application of the "-omic-" technologies may lead to a change of paradigms
      towards the application of complex mixtures in medicine and open the new field of
      phytogenomics, -proteomics and -metabolomics.

PMID- 17188481
TI  - Novel mucilage fraction of Sinapis alba L. (mustard) reduces azoxymethane-induced
      colonic aberrant crypt foci formation in F344 and Zucker obese rats.
AB  - Seeds of Sinapis alba Linn. (commonly called yellow or white mustard) and their
      components have been reported to possess anticancer properties. In this study, we
      evaluated the efficacy of a novel mucilaginous fraction of mustard seeds in
      inhibiting colonic preneoplastic changes in animal models of sporadic and obesity
      associated colon cancer. In two separate studies, male Sprague-Dawley or female
      Zucker obese rats, injected with azoxymethane (15 or 10 mg/kg body wt. once a
      week for 2 weeks, respectively), were fed AIN-93G diets with or without 5%
      mustard mucilage (MM) (w/w) for 8 weeks. Our aim was to measure the ability to
      modulate the number of aberrant crypt foci (ACF), putative preneoplastic lesions
      of the colon. The data were classified into total numbers of ACF and large ACF
      (crypt multiplicity of 4 or more). We report here that 5% MM significantly
      (p<0.05) decreased the number of total (approximately 21% inhibition) and large
      (approximately 50% inhibition) ACF in the colons of Sprague-Dawley rats compared
      to that in untreated controls. In addition, 5% MM supplemented diet significantly
      lowered (p<0.05) the number of total (approximately 63% inhibition) and large
      (approximately 60% inhibition) colonic ACF in Zucker obese rats compared to
      untreated obese rats, and had no effect on fasting plasma cholesterol or
      triglyceride levels. These results demonstrate the possible role of MM as a
      functional food against sporadic and obesity-associated colon cancer, and provide
      impetus to conduct research to understand the underlying mechanism(s) of action.

PMID- 17188484
TI  - The 1.6Mb chromosome carrying the avirulence gene AvrPik in Magnaporthe oryzae
      isolate 84R-62B is a chimera containing chromosome 1 sequences.
AB  - A genetic map was constructed previously from a cross between Magnaporthe oryzae
      isolates 84R-62B and Y93-245c-2, and genetic markers closely linked to the
      cultivar-specific avirulence (Avr) gene, AvrPik, were assigned to a 1.6Mb small
      chromosome of 84R-62B that is absent from Y93-245c-2. In the present study, the
      1.6Mb chromosome was characterized by using contour-clamped homogeneous electric
      fields (CHEF) electrophoresis and hybridization analysis. CHEF electrophoresis
      analysis showed that the 1.6Mb chromosome was inherited in Mendelian fashion, and
      co-segregated with AvrPik. Southern hybridization analysis revealed that the
      1.6Mb chromosome carried sequences only distributed to the supernumerary
      chromosome in M. oryzae isolates, as well as sequences corresponding to those in
      the supercontig 17 of chromosome 1 in the M. grisea database. Thus, we conclude
      that the Mendelian 1.6Mb chromosome is a chimera containing sequences from
      chromosome 1 and from supernumerary chromosomes in M. oryzae.

PMID- 17188483
TI  - Daldinia decipiens and Entonaema cinnabarina as fungal symbionts of Xiphydria
      wood wasps.
AB  - The identity of symbiotic fungi associated with the Xiphydria spp. wood wasps was
      investigated using DNA analysis. The fungi were isolated from the mycangia of
      adult females of X. camelus, X. prolongata and X. longicollis reared from
      colonized logs of Alnus glutinosa, Salix alba and Quercus robur, respectively.
      Sequences of rDNA and beta-tubulin were obtained. Phylogenetic analysis based on
      the NJ method showed that the isolates from X. camelus clustered with Daldinia
      decipiens, whereas those of X. prolongata belonged to Entonaema cinnabarina. In
      X. longicollis, both symbiotic fungi (D. decipiens and E. cinnabarina) have been
      found. Morphological characteristics of the anamorphs are presented. In cultures
      of D. decipiens, sympodial holoblastic, as well as annelidic, conidiation was
      observed. So far, fruit bodies of D. decipiens have only been recorded from
      Betula spp. whereas the host spectrum of its wasp vectors covers predominantly
      oaks and alders. Fruiting bodies of E. cinnabarina do not occur in Central
      Europe. This is the first report of Entonaema as a symbiotic fungus of siricid
      wood wasps.

PMID- 17188485
TI  - Non-invasive home mechanical ventilation: effectiveness and efficiency of an
      outpatient initiation protocol compared with the standard in-hospital model.
AB  - OBJECTIVE: To compare the effectiveness and efficiency of an initiation protocol
      for non-invasive home mechanical ventilation (NIHMV) carried out at a pulmonary
      outpatient clinic with the standard in-hospital model. METHODS: Prospective,
      observational study. POPULATION: 16 patients divided into two groups: (A)
      outpatient protocol (n=9); and (B) standard in-hospital initiation with an
      elective admission (n=7). INSTRUMENTATION: at baseline condition and treatment
      starting, arterial blood gases and nocturnal pulse-oximetry were performed. At
      the end of follow-up, arterial blood gases and patient compliance (ventilator's
      built-in counter) was determined. Efficiency was evaluated by calculating cost
      savings per ventilated patient for the financier and accumulated days of
      hospitalization saved. RESULTS: No differences in baseline conditions were
      observed. Ventilation was effective in the two groups: a significant decrease in
      PaCO(2) and an increase in mean nocturnal oxygen saturation were observed after
      initiating ventilation. (Group A: PaCO(2):42.9+/-1.5; SpO(2):91.9+/-1.9; Group
      B:PaCO(2):44.3+/-6; SpO(2):91.9+/-2.7). At three months the effectiveness of
      ventilation and the number of hours of ventilation was equivalent in all groups.
      The new model cut costs for the health care financier by 50%. The outpatient
      sessions saved 63 days of hospitalization. CONCLUSIONS: (1) Outpatient initiation
      is an effective and efficient alternative to the traditional in-hospital method
      for NIHMV. (2) The outpatient protocol represents a substantial saving for the
      financier.

PMID- 17188486
TI  - Bronchodilator response to adrenergic beta2-agonists: relationship to symptoms in
      an adult community.
AB  - BACKGROUND: Wheeze and chest tightness has traditionally been associated with
      enhanced bronchial responsiveness. However, no community studies are available on
      the associations between bronchodilator response and respiratory symptoms among
      adults. AIM: To examine how respiratory symptoms predict bronchodilator response.
      METHODS: An age and gender stratified random sample of all adults aged 47-48 and
      71-73 years in Bergen, Norway, were invited. The 3506 participants (69%) filled
      in questionnaires including nine symptoms and performed bronchodilator
      reversibility tests. Subjects without current anti-asthmatic medication
      performing acceptable reversibility tests were included in the analyses (n=3088).
      RESULTS: A reversibility with FEV(1) increase 12% and 200 ml was obtained in 2%
      of middle-aged and 4% of elderly subjects (p=0.001). In multiple linear
      regression analysis bronchodilatation was positively associated with wheezing
      without cold (FEV(1) increase of 1.5%, 95% CI: (0.9, 2.2)% in all participants
      and 31 ml, 95% CI: (1, 61)ml in men only) and dyspnoea climbing two flights of
      stairs (0.9%, 95% CI: (0.5,1.4)% and 12 ml, 95% CI: (1,23)ml). Chronic cough
      predicted the response negatively (-0.7%, 95% CI: (-1.3,-0.1)% and -17 ml, 95%
      CI: (-32,-2)ml). In multiple logistic regression analysis morning cough predicted
      an FEV(1) increase 12% and 200 ml (OR: 1.8, 95% CI: (1.1,2.8)). CONCLUSIONS: A
      small fraction of adults in a general population has bronchodilatation after
      salbutamol inhalation. "Wheezing without cold", "dyspnoea climbing two flights of
      stairs", and "morning cough" predict an increased bronchodilator response among
      subjects without current anti-asthmatic medications.

PMID- 17188487
TI  - Characterization of PCDD/Fs and heavy metals from MSW incineration plant in
      Harbin.
AB  - The characterization of PCDD/Fs and heavy metals in the flue gas and fly ash of
      Harbin municipal solid waste (MSW) incineration plant, located in the northeast
      of China, was investigated in this study. The MSW was treated in a twin internal
      fluidized (TIF) bed incinerator. The results indicate that the emission of
      PCDD/Fs into the environment is 0.02 ng I-TEQ/m3 and the level of PCDD/Fs in the
      fabric filter fly ash is 0.7982 ng I-TEQ/g. The leachability levels of Pb, Cd and
      Hg in the fly ash are below the limits of environmental protection standard in
      China. However, the contents of Cu, Zn, and Hg are high in the fly ash. This
      suggests that the fly ash is a hazardous waste that requires special treatment
      and disposal. The practice of more than four years of operation shows that the
      TIF bed incinerator is very suitable and practical for China.

PMID- 17188489
TI  - Roles of G-protein-coupled receptor signaling in cancer biology and gene
      transcription.
AB  - G-protein-coupled receptors (GPCRs) are ubiquitous mediators of signal
      transduction across mammalian cell membranes. Among other roles, GPCRs are known
      to regulate cellular motility, growth and differentiation, and gene
      transcription, three factors central to the biology of cancer. Because GPCRs are
      tractable drug targets, mechanisms by which receptors and their associated
      proteins impact cellular transformation and metastasis might lead to novel cancer
      therapies. Recent work has elucidated mechanisms explaining correlations between
      cancer progression and the expression of GPCRs, such as a protease-activated
      receptor (PAR1), and G-proteins, such as Galpha(12/13). Of special interest, the
      discovery of novel nuclear roles for heterotrimeric G-proteins expands the direct
      impact of G-protein signaling on processes fundamental to the pathology of
      cancer.

PMID- 17188488
TI  - Functionalization of PVC membrane with ss oligonucleotides for a potentiometric
      biosensor.
AB  - A novel application of a single stranded (ss) oligonucleotide as an active
      component of polymeric membrane in an ion-selective electrode (ISE) is described.
      The original oligonucleotides, oligo(dA)(15), modified by cholesterol,
      triphenylmethyl and hexadecyl derivatives, were immobilized into poly(vinyl
      chloride) (PVC) membrane using extraction protocol. In parallel, the adsorption
      protocol was used to immobilize unmodified oligo(dA)(15) on the PVC membrane
      based on tridodecylmethyammonium chloride (TDDMA(+)Cl(-)). Immobilization of ss
      oligonucleotide probe through spacer was more effective for the potentiometric
      detection of the hybridization between complementary oligonucleotides. It was
      found that cholesterol-oligo(dA)(15) modified membranes were sensitive toward
      complementary oligo(dT)(15) in the concentration range 2-80 nM at pH 7. An
      explanation for the detection mechanism is proposed.

PMID- 17188490
TI  - ERbeta ligands. Part 5: synthesis and structure-activity relationships of a
      series of 4'-hydroxyphenyl-aryl-carbaldehyde oxime derivatives.
AB  - A series of 4'-hydroxyphenyl-aryl-carbaldehyde oximes (5b) was prepared and found
      to have high affinity (4nM) and modest selectivity (39-fold) for estrogen
      receptor-beta (ERbeta). Substitution of one of the core rings of the scaffold
      based around these novel ligands further expanded our knowledge in the quest
      toward achieving high affinity and selectivity for ERbeta. An X-ray co-crystal of
      structure 11 revealed that the oxime moiety was mimicking the C-ring of
      genistein, as previously predicted by SAR and docking studies.

PMID- 17188491
TI  - Diastereoselective synthesis of glycosylated prolines as alpha-glucosidase
      inhibitors and organocatalyst in asymmetric aldol reaction.
AB  - 1,3-Dipolar cycloaddition of azomethine ylides and glycosyl E-olefins in presence
      of LDA led to diastereoselective formation of C-glycosylated proline esters. The
      selected esters on regioselective hydrolysis with LiOH gave C-glycosyl prolines.
      Few of the proline esters exhibited very good alpha-glucosidase inhibitory
      activity. The organocatalytic activity of the proline derivatives in a prototype
      Aldol reaction has also been investigated.

PMID- 17188492
TI  - An enhancing pituitary lesion in a young woman: a diagnostic dilemma.
AB  - Wegener's granulomatosis is a systemic small-vessel vasculitis predominantly
      involving the upper airways, lungs and kidneys. Central nervous system
      involvement is known to occur in 10% of cases, manifesting as diffuse meningeal
      involvement and cerebral granulomatous lesions, but isolated involvement of the
      pituitary is extremely rare. We describe a case of isolated pituitary involvement
      with abscess formation secondary to Wegener's granulomatosis in a 21-year-old
      woman. To the best of our knowledge this is the first reported case of pituitary
      abscess formation secondary to Wegener's granulomatosis.

PMID- 17188493
TI  - Reactivation of dormant lumbar methicillin-resistant Staphylococcus aureus
      osteomyelitis after 12 years.
AB  - The adequate treatment of methicillin-resistant Staphylococcus aureus (MRSA)
      osteomyelitis has intrigued clinicians for some time. As the resistance of these
      pathogens, coupled with the increase in community-acquired cases, continues
      steadily to rise, clinicians are finding it useful to employ multi-modal
      approaches for efficacious treatment. The authors present a single case report of
      a patient with recurrent MRSA osteomyelitis, lumbar paraspinal and epidural
      abscess. He was found to have decreased muscle strength and was hyporeflexic in
      the involved extremity. Serum testing demonstrated MRSA bacteremia. Neuroimaging
      studies revealed evidence of paraspinal abscess and a presumed herniated nucleus
      pulposus at the L5/S1 interspace with significant nerve root compromise. Despite
      antimicrobials, his symptoms persisted, necessitating surgical exploration. At
      surgery, paraspinal and epidural abscesses were encountered and debrided;
      however, no herniated disc was visualized. This case demonstrates the diagnostic
      and therapeutic dilemmas with which these lesions present. We postulate that the
      MRSA osteomyelitis/discitis pathogens were walled off in the disc space and
      subsequently inoculated the soft tissues with ensuing bacteremia. We concur that
      antimicrobial treatment should be the first line of therapy for these patients;
      however, surgical debridements and cautious spinal instrumentation should be
      employed where appropriate.

PMID- 17188494
TI  - High grade glioma in a focal cortical dysplastic lesion.
AB  - A 61-year-old woman presented in 1999 with a recent onset of left-sided focal
      clonic seizures with associated vague speech arrests. A computerised tomography
      (CT) scan revealed a hypoattenuated non-enhancing lesion within her right
      temporal lobe which was biopsied and the histopathological features were reported
      to be consistent with a hamartoma, reminiscent of tuberous sclerosis. Her
      seizures remained partially controlled with phenytoin and carbamazepine. She
      presented again 2 years later with an increase in the frequency of her seizures.
      A magnetic resonance scan of her brain demonstrated a homogenously enhancing mass
      lesion in her right temporo-parietal lobe. An initial lobectomy showed a
      hamartomatous lesion on histology but a subsequent sample obtained from a wide
      resection carried out when there was further worsening of her condition revealed
      a grade IV astrocytoma within a focal cortical dysplastic lesion. Our case
      highlights the importance of considering the possibility of a cortical dysplastic
      lesion harbouring a malignancy and the need for further research to explore the
      behaviour of these malformative lesions.

PMID- 17188495
TI  - Obesity and knee arthroplasty.
AB  - Obesity has been shown to be a risk factor for knee osteoarthritis. Total knee
      arthroplasty in the obese patient has given rise to some controversy in terms of
      perioperative risks, and the longevity of the implants. We reviewed the salient
      literature on this subject regarding the impact of obesity on the knee, the
      outcome of TKA in the obese patient, and on the effect of TKA on pre-existing
      obesity. While increased risk of complications and early implant failure has been
      shown by some studies in the morbidly obese, there is no definite cut-off in Body
      Mass Index which accurately separates high-risk from low-risk individuals,
      although there is evidence that heavier patients are at greater risk. We have
      seen that although postoperative scores are lower in the obese group, these
      patients may derive considerable improvement in pain following TKA. While not
      condoning the obese patient with knee arthritis being denied an effective pain
      relieving procedure, we stress the importance of appropriate risk-counselling of
      these patients, and allowance within the healthcare system for the extra
      financial and service implications placed by the obese TKA patient.

PMID- 17188496
TI  - Carinatumins A-C, new alkaloids from Lycopodium carinatum inhibiting
      acetylcholinesterase.
AB  - Three new Lycopodium alkaloids, carinatumins A-C (1-3), have been isolated from
      the club moss Lycopodium carinatum. Structures and stereochemistry of 1-3 were
      elucidated on the basis of 2D NMR correlations. Carinatumins A (1) and B (2)
      exhibited a potent inhibitory activity against acetylcholinesterase.

PMID- 17188497
TI  - B cells play a cooperative role via CD40L-CD40 interaction in T cell-mediated
      experimental autoimmune neuritis in Lewis rats.
AB  - The expression of co-stimulatory molecules CD40 and CD40L was examined over the
      course of experimental autoimmune neuritis (EAN) induced in Lewis rats by
      immunization with bovine peripheral nerve myelin. In draining lymph nodes,
      highest level of CD40L expression was seen on day 7 post immunization (p.i.),
      i.e. before onset of clinical signs of EAN, while CD40 expression was increased
      on day 14 p.i., i.e. at peak of clinical disease. In contrast, both CD40 and
      CD40L expressing cells in sciatic nerves, a target organ of EAN, peaked on day 14
      p.i., large numbers of both expressing cells were mainly detected on day 14-21
      p.i. After co-culture with EAN rat B cells bearing CD40, P0 peptide 180-199
      specific T cell line cells exhibited a rapid down-regulation of CD40L expression.
      Furthermore, EAN rats had enhanced P0 peptide 180-199-specific antibody responses
      on day 14 p.i., which might have contributed to their aggravated EAN and further
      demonstrated the role of antibodies in EAN. The results indicate that CD40L-CD40
      interactions are involved in the initiation of the antigen-specific T cell
      responses associated with the generation and development of EAN, and may mediate
      autoantibody production in EAN. Evidently, B cells play a cooperative role via
      CD40L-CD40 interaction in T cell-mediated EAN of Lewis rats.

PMID- 17188498
TI  - The role of matrix metalloproteinases in infant traumatic brain injury.
AB  - Matrix metalloproteinases (MMPs) play an essential role in tissue repair, cell
      death and morphogenesis and may constitute therapeutic targets for acute brain
      injuries. In this study, we investigated the expression of 72 kDa and 92 kDa
      collagenases MMP-2 and MMP-9 at transcriptional, functional and protein
      expression level following traumatic brain injury in infant rats. Seven-day-old
      Wistar rats were subjected to head trauma using a weight drop device. Pups were
      sacrificed at defined time points (2-72 h) after trauma and brains were processed
      for molecular studies (semiquantitative and real-time PCR, Western blot, gelatin
      zymography) and histology. Trauma triggered widespread cell death in the cortex,
      basal ganglia and white matter. mRNA levels for MMP-2 and -9 were increased in
      the brain at 12-72 h after trauma. Protein expression of the analyzed MMPs and
      activity of MMP-2 were increased at 12 h and peaked at 24 h after trauma.
      Intraperitoneal injection of GM6001 (Ilomastat), an MMP inhibitor, 2 h after
      trauma, substantially attenuated traumatic brain injury in a dose-dependent
      manner. These findings causally link the MMPs to trauma-induced neuronal cell
      death in the immature rodent brain. MMPs might serve as useful targets for
      therapeutic approaches aimed at preserving neuronal function in the immature
      brain in the context of mechanical injury.

PMID- 17188499
TI  - The importance of A9 dopaminergic neurons in mediating the functional benefits of
      fetal ventral mesencephalon transplants and levodopa-induced dyskinesias.
AB  - Intrastriatal transplantation of fetal ventral mesencephalon (VM) tissue provides
      the potential to alleviate motor symptoms of Parkinson's disease (PD) and
      levodopa-induced dyskinesia (LID). However, the degree of recovery varies among
      individuals with an incidence of "off-phase", graft-induced dyskinesia (GID) in
      some patients. We hypothesised that this variability is due to the heterogeneous
      nature of dopaminergic neurons in the transplant. We therefore investigated this
      in the unilateral 6-hydroxydopamine-lesioned rat model of PD. These animals were
      primed to develop LID and then transplanted with fetal VM into the caudal aspects
      of the striatum. No GID was observed but in a significant number of animals the
      transplants ameliorated LID. There was a correlation between the degree of
      behavioural and LID recovery with the number of A9 dopaminergic neurons in the
      transplant, based on their expression of a G-protein-coupled inward rectifying
      current potassium channel (Girk2). Furthermore, we showed that LID development is
      related to an abnormal expression profile of cyclin-dependent kinase 5 (Cdk5) and
      dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) in the striatum
      and that intrastriatal VM transplants normalised both Cdk5 expression and DARPP
      32 phosphorylation in animals exhibiting functional improvement. These results
      suggest that an A9 dopaminergic neuron-enriched transplant may be the key to an
      effective PD cell replacement therapy through normalisation of the altered
      striatal expression of Cdk5/DARPP-32.

PMID- 17188500
TI  - Activation of caspase-1 dependent interleukins in developmental brain trauma.
AB  - Focal mechanical cortical trauma triggers diffuse apoptotic neurodegeneration in
      the developing rat brain which is associated with invasion of brain tissue with
      inflammatory mediators. We hypothesized that caspase-1 and the two caspase-1
      processed cytokines, interleukin (IL)-1beta and IL-18, are involved in trauma
      induced neuronal cell death in the developing brain. 7-day-old Wistar rats or
      C57/BL6 mice were subjected to head trauma using a weight drop device. Animals
      were sacrificed at defined time points following trauma and brains were processed
      for histology and molecular analyses. Neuronal cell death in the immature brain
      peaked at 12-24 h and was accompanied by a marked increase of mRNA and protein
      levels for caspase-1, IL-1beta and IL-18 within 2 to 12 h following the injury.
      Caspase-1 levels were elevated for 72 h, whereas IL-1beta decreased earlier at 48
      h. IL-18 remained high over a period of 3 days and decreased to normal levels by
      day 7 after the injury. Intraperitoneal injection of recombinant human IL-18
      binding protein (IL-18BP), a specific inhibitor of IL-18, attenuated traumatic
      brain injury. Mice deficient in IL-18 (IL-18-/-) were protected against trauma
      induced brain damage. These findings indicate that IL-18 is involved in trauma
      induced neuronal cell death in the immature rodent brain and might serve as a
      potential therapeutic target.

PMID- 17188501
TI  - Blood-brain barrier disruption results in delayed functional and structural
      alterations in the rat neocortex.
AB  - Disruption of the blood-brain barrier (BBB) is a characteristic finding in common
      neurological disorders. Human data suggest BBB disruption may underlie cerebral
      dysfunction. Animal experiments show the development of epileptiform activity
      following BBB breakdown. In the present study we investigated the
      neurophysiological, structural and functional consequences of BBB disruption.
      Adult rats underwent focal BBB disruption in the rat sensory-motor cortex using
      the bile salt sodium deoxycholate (DOC). Magnetic resonance imaging in-vivo
      showed an early BBB disruption with delayed reduction in cortical volume. This
      was associated with a reduced number of neurons and an increased number of
      astrocytes. In-vitro experiments showed that the threshold for spreading
      depression and the propagation velocity of the evoked epileptic potentials were
      increased 1 month after treatment. Furthermore, animals' motor functions
      deteriorated during the first few weeks following BBB disruption. Treatment with
      serum albumin resulted in a similar cell loss confirming that the effect of DOC
      was due to opening of the BBB. Our findings suggest that delayed
      neurodegeneration and functional impairment occur following the development of
      the epileptic focus in the BBB-permeable cerebral cortex.

PMID- 17188502
TI  - Early motor development is abnormal in complexin 1 knockout mice.
AB  - Complexin I expression is dysregulated in a number of neurological diseases
      including schizophrenia and depression. Adult complexin 1 knockout (Cplx1(-/-))
      mice are severely ataxic and show deficits in exploration and emotional
      reactivity. Here, we evaluated early behavioural development of Cplx1(-/-) mice.
      Cplx1(-/-) mice showed marked abnormalities. They develop ataxia by post-natal
      day 7 (P7), and by P21 show marked deficits in tasks requiring postural skills
      and complex movement. These deficits are consistent with abnormalities in sensory
      and motor development found in infants that develop schizophrenia in later life.
      A role for complexin I depletion should be considered in diseases where deficits
      in early sensory and motor development exist, such as autism and schizophrenia.

PMID- 17188503
TI  - A pathogenetic hypothesis of Unverricht-Lundborg disease onset and progression.
AB  - Unverricht-Lundborg disease (EPM1), the most common progressive myoclonic
      epilepsy, is associated with a defect of cystatin B (CSTB), a protease inhibitor.
      We used CSTB knockout mice to test the hypothesis that EPM1 onset is related to a
      latent hyperexcitability and that progression depends on higher susceptibility to
      seizure-induced cell damage. Hippocampal slices prepared from CSTB-deficient mice
      were hyperexcitable, as they responded to afferent stimuli in CA1 with multiple
      population spikes and kainate perfusion provoked the appearance of epileptic-like
      activity earlier than in WT mice. This hyperexcitability may depend on loss of
      inhibition, because the density of GABA-immunoreactive cells was reduced in the
      hippocampus of CSTB knockouts. In vivo, CSTB-deficient mice treated with kainate
      displayed increased susceptibility to seizures, with shorter latency to seizure
      onset and increased seizure severity compared with WT littermates. Furthermore, a
      greater degree of neuronal damage was observed in CSTB-deficient than in WT mice
      after seizures of identical grade, indicating increased susceptibility to seizure
      induced cell death.

PMID- 17188504
TI  - Angiogenesis and antiangiogenic therapy in hematologic malignancies.
AB  - Angiogenesis, the generation of new blood capillaries from preexisting blood
      vessels, is tightly regulated in the adult organism. Although many of the initial
      studies were performed on solid tumors, increasing evidence indicates that
      angiogenesis also plays an important role in hematologic malignancies.
      Overexpression of angiogenic factors in particular VEGF and bFGF in most
      hematologic malignancies may explain the increased angiogenesis found in these
      malignancies and correlate with poor prognosis as well as decreased overall
      survival. In this review, we focus on the current literature of angiogenesis and
      antiangiogenic therapy in hematologic malignancies, and finally describe advances
      and potential challenges in antiangiogenic treatment in hematologic malignancies.

PMID- 17188505
TI  - Impact of breast cancer survivorship on quality of life in older women.
AB  - Quality of life (QOL) is an important outcome for cancer survivors; but although
      age is a major risk factor, most breast cancer survivorship studies are conducted
      with younger women. The objective of our study was to compare QOL in a sample of
      older breast cancer survivors to a sample of older women who were never diagnosed
      with breast cancer. A sample of 127 older breast cancer survivors as identified
      by a cancer registry was compared to a demographically equated sample of 87 older
      women participating in an epidemiological study. Both groups completed a
      questionnaire and participated in an interview to measure QOL. The older breast
      cancer survivors scored worse in the Medical Outcomes Study-Short Form, a measure
      of health-related QOL. Survivors reported no more depressive symptoms or anxious
      mood than the comparison group, but scored lower in measures of positive
      psychosocial well-being, including life satisfaction, mastery, and spiritual well
      being, and reported more depressed mood and days affected by fatigue. Older
      breast cancer survivors show multiple indications of decrements in their health
      related quality of life, and lower psychosocial well-being than the comparison
      group. These decrements may represent deficits in reserve capacity that
      predispose older cancer survivors to functional disability but may not be readily
      detected in typical clinical evaluations given the multiple impairments common in
      geriatric populations. Results suggest a need for greater attention to promoting
      functioning and psychological well-being among older cancer survivors, even when
      they may not have obvious cancer-related medical complications.

PMID- 17188507
TI  - APPI-MS: effects of mobile phases and VUV lamps on the detection of PAH
      compounds.
AB  - The technique of atmospheric pressure photoionization (APPI) has several
      advantages over electrospray ionization (ESI) and atmospheric pressure chemical
      ionization (APCI), including efficient ionization of nonpolar or low charge
      affinity compounds, reduced susceptibility to ion suppression, high sensitivity,
      and large linear dynamic range. These benefits are greatest at low flow rates
      (i.e., <or=100 microL/min), while at a higher flow, photon absorption and ion
      molecule reactions become significant. Under certain circumstances, APPI signal
      and S/N have been observed to excel at higher flow, which may be due to a
      nonphotoionzation mechanism. To better understand APPI at higher flow rates, we
      have selected three lamps (Xe, Kr, and Ar) and four mobile phases typical for
      reverse-phase, high-pressure liquid chromatography: acetonitrile, methanol, (1:1)
      acetonitrile:water and (1:1) methanol:water. As test compounds, three
      polyaromatic hydrocarbons are studied: benzo[a]pyrene, indeno[1,2,3-c, d]pyrene
      and benz[a]anthracene. We find that solvent photoabsorption cross-section is not
      the only parameter in explaining relative signal intensity, but that solvent
      photo-ion chemistry can also play a significant role. Three conclusions from this
      investigation are: (1) methanol photoionization leads to protonated methanol
      clusters that can result in chemical ionization of analyte molecule; (2) use of
      the Ar lamp often results in greater signal and S/N; (3) acetonitrile
      photoionization is less efficient and resulting clusters are too strongly bound
      to chemically ionize the analyte efficiently, so that analyte ion formation is
      dominated by direct photoionization.

PMID- 17188508
TI  - Study of the enhancement of dipolar resonant excitation by linear ion trap
      simulations.
AB  - Resolution improvements in dipolar resonant excitation have been examined in a
      round-rod quadrupolar collision cell for values of the Mathieu characteristic
      exponent beta equal to n/p, where n and m are small integers (prime beta values)
      versus other beta values where n and p are not small (ordinary beta values). The
      trajectories of ions moving in the time-varying electric fields of a quadrupole
      with and without buffer-gas molecules were calculated to determine the
      relationship of prime and ordinary beta values to frequency resolution for
      resonant ion excitation and ejection. For prime beta values, the ion trajectory
      in the hyperbolic quadrupole field will be exactly periodic with a period of at
      most 4 pi p/Omega, where Omega is the angular frequency of the main drive radio
      frequency (RF) potential. Ion trajectory simulations with prime beta versus
      ordinary beta values show that the motion of ions with prime beta values have
      simpler trajectories of shorter periods. Frequency response profiles (FRPs) for
      round-rod quadrupoles at zero pressure show that dipolar resonant excitations
      with prime beta values exhibit significantly narrower bandwidths than those with
      ordinary beta values. Simulations show that at 0.05 to 0.8 mTorr of nitrogen, it
      is possible to reduce the FRP bandwidth by 20% (measured at 50% depth).

PMID- 17188506
TI  - Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without
      antigens: multiclonal responses that are extremely lytic if triggered and short
      lived after cytokine withdrawal.
AB  - The purpose of these studies was to determine the minimal requirements to induce
      granzyme B, cytotoxic granules and perforin-dependent lytic capacity. To our
      surprise, both IL-2 and IL-15 induced not only proliferation, but also profound
      granzyme B and lytic capacity from CD8+ T cells in the absence of antigen or TCR
      stimulation. Mouse splenocytes were incubated with mouse r-IL-2 or r-IL-15 for
      three days, tested by anti-CD3 redirected lysis and examined for intracellular
      granzyme B and for T cell activation markers. With 10(-8) M IL-2 or IL-15, there
      was excellent lytic activity at 1:1 effector to target ratios mediated by T cells
      from wild-type but not from perforin-gene-ablated mice, consistent with
      multiclonal activation. Lower interleukin concentrations induced less lytic
      activity. Granzyme B was undetectable on day 0, and greatly elevated on day 3 in
      CD44hi CD8+ T cells as detected by flow cytometry. Cytokines alone elevated the
      granzyme B as much as concanavalin A combined with the cytokines. Some ex vivo
      CD8+ T cells were CD122+, as were the cultured granzyme B+ cells, thus both
      populations had low-affinity receptors for the interleukins. Only some of the
      activated cells were proliferating as detected by CFSE labeling. When the
      cytokines were withdrawn, the cells lost lytic activity within 24 h and then
      within the next 24 h, died. Our results suggest that high concentrations of
      either IL-2 or IL-15 will activate the lytic capacity and granzyme B expression
      of many T cells and that antigen recognition is not required.

PMID- 17188509
TI  - Survival response-linked Pyk2 activation during potassium depletion-induced
      apoptosis of cerebellar granule neurons.
AB  - Numerous extracellular stimuli trigger trans-autophosphorylation at Tyr402 of
      Pyk2, inducing its activation. Pyk2 is a key mediator of several signaling
      pathways and has been implicated in apoptosis induced by specific stress signals.
      We investigated whether Pyk2 participates in cerebellar granule neuron (CGN)
      apoptosis induced by the suppression of membrane depolarization. We demonstrate
      that shifting CGN cultures from 25 mM to 5 mM KCl-containing medium induces an
      early, transient 70% increase in phosphorylated Tyr402 and Tyr580 Pyk2 levels
      that is triggered by Ca(2+) released from intracellular stores and mediated by
      calmodulin (CaM). Overexpression of Pyk2 increases CGN survival after 24 h by 70%
      compared to the control, thus suggesting that Pyk2 is involved in an anti
      apoptotic response to K+ lowering. Furthermore, we show that CGN grown in K25
      medium exhibit detectable CaM-dependent Pyk2 activity. When silencing Pyk2
      activity by expressing a dominant-negative form, only 40% of the transfected
      neurons were alive 24 h after transfection when compared to the control. Overall,
      the present findings demonstrate for the first time that Pyk2 is a critical
      mediator of CGN survival.

PMID- 17188510
TI  - Properties of human Cav2.1 channel with a spinocerebellar ataxia type 6 mutation
      expressed in Purkinje cells.
AB  - Spinocerebellar ataxia type 6 (SCA6) is caused by polyglutamine expansion in P/Q
      type Ca2+ channels (Ca(v)2.1) and is characterized by predominant degeneration of
      cerebellar Purkinje cells. To characterize the Ca(v)2.1 channel with an SCA6
      mutation in cerebellar Purkinje cells, we have generated knock-in mouse models
      that express human Ca(v)2.1 with 28 polyglutamine repeats (disease range) and
      with 13 polyglutamine repeats (normal range). Patch-clamp recordings of the
      Purkinje cells from homozygous control or SCA6 knock-in mice revealed a non
      inactivating current that is highly sensitive to a spider toxin omega-Agatoxin
      IVA, indicating that the human Ca(v)2.1 expressed in Purkinje cells exhibits
      typical P-type properties in contrast to the previous data showing Q-type
      properties, when it was expressed in cultured cell lines. Furthermore, the
      voltage dependence of activation and inactivation and current density were not
      different between SCA6 and control, though these properties were altered in
      previous reports using non-neuronal cells as expression systems. Therefore, our
      results do not support the notion that the alteration of the channel properties
      may underlie the pathogenic mechanism of SCA6.

PMID- 17188511
TI  - Expression, purification, and characterization of secreted recombinant human
      insulin-like growth factor-binding protein-6 in methylotrophic yeast Pichia
      pastoris.
AB  - The mitogenic and metabolic activities of insulin-like growth factors (IGF) are
      modulated by a family of six high-affinity IGF-binding proteins (IGFBPs). This
      study describes the secretion and purification of the recombinant human IGFBP-6
      expressed in methylotrophic yeast Pichia pastoris. In this research, a multicopy
      expression plasmid pA-O815/3xIGFBP-6 containing 3 copies of human IGFBP-6
      expression cassette was constructed and transformed into P. pastoris GS115. The
      encoding sequence of alpha-factor leading peptide fused in-frame at the 5' end of
      human IGFBP-6 open reading frame and led expressed IGFBP-6 into the secretory
      pathway. After transformed cells were induced with methanol, medium supernatant
      was analyzed by SDS-PAGE and Western blotting. The two major protein bands of
      approximately 30 and approximately 18kDa were detected. The protein of
      approximately 30kDa was confirmed to be the glycosylated recombinant human IGFBP
      6 (rhIGFBP-6), which was partially proteolyzed by protease Kex2 to produce a
      approximately 18kDa fragment. Approximately 95% homogeneity of the soluble form
      of 30kDa rhIGFBP-6 were achieved by two-step purification procedure using ion
      exchange chromatography and then hydrophobic-interaction chromatography. The
      rhIGFBP-6 could be distributed to all of the cell body when cultured MDA-MB-231
      cell with rhIGFBP-6 and the activities of rhIGFBP-6 were assayed by
      [(3)H]thymidine incorporation, which revealed that rhIGFBP-6 inhibited IGF-II
      stimulated cell proliferation. Our results demonstrated that functional rhIGFBP-6
      can be produced in sufficient quantities by using P. pastoris for further
      structural and functional studies.

PMID- 17188512
TI  - Modeling the charge distribution at metal sites in proteins for molecular
      dynamics simulations.
AB  - Almost half of the proteome of living organisms is constituted of
      metalloproteins. Unfortunately, the ability of the current generation of
      molecular dynamics pairwise-additive forcefields to properly describe metal
      pockets is severely lacking due to the intrinsic difficulty of handling
      polarization and charge transfer contributions. In order to improve the
      description of metalloproteins, a simple reparameterization strategy is proposed
      herein that does not involve artificial constraints. Specifically, a non-bonded
      quantum mechanical-based model is used to capture the mean polarization and
      charge transfer contributions to the interatomic forces within the metal site.
      The present approach is demonstrated to provide enough accuracy to maintain the
      integrity of the metal pocket for a variety of metalloproteins during extended
      (multi-nanosecond) molecular dynamics simulations. The method enables the
      sampling of small conformational changes and the relaxation of local frustrations
      in NMR structures.

PMID- 17188513
TI  - Carbohydrate binding properties and carbohydrate induced conformational switch in
      sheep secretory glycoprotein (SPS-40): crystal structures of four complexes of
      SPS-40 with chitin-like oligosaccharides.
AB  - Crystal structures of four complexes of sheep secretory glycoprotein (SPS-40)
      with N-acetylglucosamine oligosaccharides (GlcNAc(n), (n=3-6)) have been
      determined at moderate resolutions. The binding studies of SPS-40 have been
      carried out using fluorescence spectroscopy and Surface Plasmon Resonance (SPR).
      Structure determinations of four complexes have shown a novel binding pattern of
      GlcNAc(n) molecules to SPS-40. The results indicate that the most preferred
      recognition region in the carbohydrate binding groove in SPS-40 is at subsites -4
      to -2 among which subsite -2 provides the maximum interactions with carbohydrate
      residues. These structures have also shown that the interactions of GlcNAc3 and
      GlcNAc4 do not perturb the protein structure and those of GlcNAc5 induce partial
      conformational changes while in the case of GlcNAc6 the partially closed binding
      groove opened up completely. As in other SPX-40 structures, SPS-40 structure
      contains three overlapping flexible surface segments, His188-His197, Phe202
      Arg212 and Phe244-Pro260 with several charged residues protruding outwardly. It
      creates a cluster of positive charges with a flexible base thus indicating a good
      scope of promoting the intermolecular interactions. This protein is glycosylated
      at Asn39 and may recognize other receptors having sugar binding sites. It appears
      that SPS-40 may involve both carbohydrate and protein bindings. The systematic
      carbohydrate-binding studies and the detailed structural results of four protein
      carbohydrate complexes provide an excellent insight into the mechanism of
      carbohydrate binding. These are the first studies of this kind on secretory
      glycoproteins and their interactions with carbohydrates.

PMID- 17188514
TI  - Negative congruency effects: a test of the inhibition account.
AB  - Masked priming experiments occasionally revealed surprising effects: Participants
      responded slower for congruent compared to incongruent primes. This negative
      congruency effect (NCE) was ascribed to inhibition of prime-induced activation
      [Eimer, M., & Schlaghecken, F. (2003). Response faciliation and inhibition in
      subliminal priming. Biological Psychology, 64, 7-26.] that sets in if the prime
      activation is sufficiently strong. The current study tests this assumption by
      implementing manipulations designed to vary the amount of prime-induced
      activation in three experiments. In Experiments 1 and 3, NCEs were observed
      despite reduced prime-induced activation. Experiment 2 revealed no NCE with at
      least similar prime strength. Thus, the amount of prime activation did not
      predict whether or not NCEs occurred. The findings are discussed with regard to
      the inhibition account and the recently proposed account of mask-induced
      activation [cf. Lleras, A., & Enns, J. T. (2004). Negative compatibility or
      object updating? A cautionary tale of mask-dependent priming. Journal of
      Experimental Psychology: General, 133, 475-493; Verleger, R., Jaskowski, P.,
      Aydemir, A., van der Lubbe, R. H. J., & Groen, M. (2004). Qualitative differences
      between conscious and nonconscious processing? On inverse priming induced by
      masked arrows. Journal of Experimental Psychology: General, 133, 494-515].

PMID- 17188516
TI  - Age-related water diffusion changes in human brain: a voxel-based approach.
AB  - The aim of the present study is to investigate age-related changes in water self
      diffusion in cerebral white matter by analysing diffusion-weighted MRI from a
      sample of 54 healthy volunteers. A voxel-based analysis of the relative
      anisotropy and the apparent diffusion coefficients was performed by applying an
      optimized normalization protocol. Linear regression analysis revealed significant
      correlations with age in the corpus callosum, prefrontal regions, the internal
      capsule, the hippocampal complex, and the putamen. However, in other regions,
      such as those surrounding the ventricles, the insula, or the inferior frontal
      plane, significant correlations between age and ADC were observed, presumably as
      a result of morphological age-related variations. A mask procedure was carried
      out in order to distinguish between morphological involvement and real age
      related white matter changes. Our results indicate that in interpreting the
      changes in each significant region it is necessary to proceed with precaution
      because the voxel-based statistical analysis might yield a mixture of two
      effects: (i) morphological changes that remain after the normalization procedure
      and (ii) actual diffusivity parameter changes. Anatomically defined regions of
      interest may help us to minimize morphologic involvement and draw comparisons
      with findings previously published.

PMID- 17188515
TI  - Spatio-temporal information analysis of event-related BOLD responses.
AB  - A new approach for analysis of event-related fMRI (BOLD) signals is proposed. The
      technique is based on measures from information theory and is used both for
      spatial localization of task-related activity, as well as for extracting temporal
      information regarding the task-dependent propagation of activation across
      different brain regions. This approach enables whole brain visualization of
      voxels (areas) most involved in coding of a specific task condition, the time at
      which they are most informative about the condition, as well as their average
      amplitude at that preferred time. The approach does not require prior assumptions
      about the shape of the hemodynamic response function (HRF) nor about linear
      relations between BOLD response and presented stimuli (or task conditions). We
      show that relative delays between different brain regions can also be computed
      without prior knowledge of the experimental design, suggesting a general method
      that could be applied for analysis of differential time delays that occur during
      natural, uncontrolled conditions. Here we analyze BOLD signals recorded during
      performance of a motor learning task. We show that, during motor learning, the
      BOLD response of unimodal motor cortical areas precedes the response in higher
      order multimodal association areas, including posterior parietal cortex. Brain
      areas found to be associated with reduced activity during motor learning,
      predominantly in prefrontal brain regions, are informative about the task
      typically at significantly later times.

PMID- 17188518
TI  - Neural correlates of response reversal: considering acquisition.
AB  - Previous work on response reversal has typically used a single pair of stimuli
      that serially reverse. This conflation of acquisition and reversal processes has
      prevented an examination of the functional role of neural systems implicated in
      response reversal during acquisition despite the relevance of such data in
      evaluating accounts of response reversal. In the current study, participants
      encountered 16 independent reversing stimulus pairs in the context of a
      probabilistic response reversal paradigm. Functional regions of interest
      identified as involved in response reversal through a contrast used in the
      previous literature (punished errors made in the reversal phase versus rewarded
      correct responses), were interrogated across conditions. Consistent with
      suggestions that middle frontal cortex codes reward, this region showed
      significantly greater responses to rewarded rather than punished trials
      irrespective of accuracy or learning phase (acquisition or reversal). Consistent
      with the suggestion that this coding of the expectation of reinforcement is
      acquired via input from the amygdala, we observed significant positive
      connectivity between activity within the amygdala and a region of rostral
      anterior cingulate cortex highly proximal to this region of middle frontal/mesial
      prefrontal cortex. In contrast, inferior frontal cortex, anterior cingulate
      cortex and caudate showed greater responses to punished errors than to the
      rewarded correct responses. These three regions also showed significant
      activation to rewarded errors during acquisition, in contrast to positions
      suggesting that inferior frontal cortex represents punishment or suppresses
      previously rewarded responses. Moreover, a connectivity analysis with an anterior
      cingulate cortex seed revealed highly significant positive connectivity among
      them. The implications of these data for recent accounts of response reversal and
      of response reversal impairments in specific neuropsychiatric populations are
      discussed.

PMID- 17188517
TI  - Acute prefrontal cortex TMS in healthy volunteers: effects on brain 11C-alphaMtrp
      trapping.
AB  - High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left
      dorsolateral prefrontal cortex (LDLPFC) is a technique with purported efficacy as
      a treatment for major depression. Here, we assessed in vivo, in healthy
      volunteers, the effect of acute rTMS of the LDLPFC, relative to the stimulation
      of the left occipital cortex (LOC), on brain regional serotonin synthesis
      capacity, using the [(11)C]-alpha-methyl-tryptophan ((11)C-alphaMtrp)/PET method.
      Ten subjects were studied twice, once following rTMS of the LDLPFC and once
      following rTMS of the LOC in a randomized counterbalanced order. Three blocks of
      15 trains of 10 Hz rTMS were delivered 10 min apart. Behavioural and autonomic
      measures were recorded before and after each rTMS session. Comparisons of TMS
      related changes in regional normalized brain uptake and trapping of (11)C
      alphaMtrp (K*) values were carried out using SPM99. Statistically significant
      regional differences were identified on the basis of an extent threshold of 50
      voxels, with a peak threshold of p=0.005 uncorrected. Behavioural and autonomic
      measures were unaffected by rTMS. Relative to LOC stimulation, LDLPFC rTMS was
      associated with marked changes in normalized K* in limbic areas, with
      significantly lower values in the left parahippocampal gyrus (BA 28) and the
      right insula (BA 13), and higher values in the right cingulate gyrus (BA 31) and
      cuneus (BA 18). These findings indicate that acute rTMS of the LDLPFC in healthy
      volunteers modulates aspects of tryptophan/5-HT metabolism in limbic areas. Such
      adaptive changes may contribute to the mechanism of action of prefrontal rTMS in
      major depression.

PMID- 17188519
TI  - Simultaneous laser Doppler flowmetry and arterial spin labeling MRI for
      measurement of functional perfusion changes in the cortex.
AB  - This study compares laser Doppler flowmetry (LDF) and arterial spin labeling
      (ASL) for the measurement of functional changes in cerebral blood flow (CBF). The
      two methods were applied concurrently in a paradigm of electrical whisker
      stimulation in the anaesthetised rat. Multi-channel LDF was used, with each
      channel corresponding to different fiber separation (and thus measurement depth).
      Continuous ASL was applied using separate imaging and labeling coils at 3 T.
      Careful experimental set up ensured that both techniques recorded from spatially
      concordant regions of the barrel cortex, where functional responses were maximal.
      Strong correlations were demonstrated between CBF changes measured by each LDF
      channel and ASL in terms of maximum response magnitude and response time-course
      within a 6-s-long temporal resolution imposed by ASL. Quantitatively, the
      measurements of the most superficial LDF channels agreed strongly with those of
      ASL, whereas the deeper LDF channels underestimated consistently the ASL
      measurement. It was thus confirmed that LDF quantifies CBF changes consistently
      at a superficial level, and for this case the two methods provided concordant
      measures of functional CBF changes, despite their essentially different physical
      principles and spatiotemporal characteristics.

PMID- 17188520
TI  - Formation of new genes explains lower intron density in mammalian Rhodopsin G
      protein-coupled receptors.
AB  - Mammalian G protein-coupled receptor (GPCR) genes are characterised by a large
      proportion of intronless genes or a lower density of introns when compared with
      GPCRs of invertebrates. It is unclear which mechanisms have influenced intron
      density in this protein family, which is one of the largest in the mammalian
      genomes. We used a combination of Hidden Markov Models (HMM) and BLAST searches
      to establish the comprehensive repertoire of Rhodopsin GPCRs from seven species
      and performed overall alignments and phylogenetic analysis using the maximum
      parsimony method for over 1400 receptors in 12 subgroups. We identified 14
      different Ancestral Receptor Groups (ARGs) that have members in both vertebrate
      and invertebrate species. We found that there exists a remarkable difference in
      the intron density among ancestral and new Rhodopsin GPCRs. The intron density
      among ARGs members was more than 3.5-fold higher than that within non-ARG members
      and more than 2-fold higher when considering only the 7TM region. This suggests
      that the new GPCR genes have been predominantly formed intronless while the
      ancestral receptors likely accumulated introns during their evolution. Many of
      the intron positions found in mammalian ARG receptor sequences were found to be
      present in orthologue invertebrate receptors suggesting that these intron
      positions are ancient. This analysis also revealed that one intron position is
      much more frequent than any other position and it is common for a number of
      phylogenetically different Rhodopsin GPCR groups. This intron position lies
      within a functionally important, conserved, DRY motif which may form a proto
      splice site that could contribute to positional intron insertion. Moreover, we
      have found that other receptor motifs, similar to DRY, also contain introns
      between the second and third nucleotide of the arginine codon which also forms a
      proto-splice site. Our analysis presents compelling evidence that there was not a
      major loss of introns in mammalian GPCRs and formation of new GPCRs among mammals
      explains why these have fewer introns compared to invertebrate GPCRs. We also
      discuss and speculate about the possible role of different RNA- and DNA-based
      mechanisms of intron insertion and loss.

PMID- 17188521
TI  - Reticulate phylogenetics and phytogeographical structure of Heliosperma
      (Sileneae, Caryophyllaceae) inferred from chloroplast and nuclear DNA sequences.
AB  - The Balkan Peninsula is known to be one of the most diverse and species-rich
      parts of Europe, but its biota has gained much less attention in phylogenetic and
      evolutionary studies compared to other southern European mountain systems. We
      used nuclear ribosomal internal transcribed spacer (ITS) sequences and intron
      sequences of the chloroplast gene rps16 to examine phylogenetic and
      biogeographical patterns within the genus Heliosperma (Sileneae,
      Caryophyllaceae). The ITS and rps16 intron sequences both support monophyly of
      Heliosperma, but the data are not conclusive with regard to its exact origin.
      Three strongly supported clades are found in both data sets, corresponding to
      Heliosperma alpestre, Heliosperma macranthum and the Heliosperma pusillum clade,
      including all other taxa. The interrelationships among these three differ between
      the nuclear and the plastid data sets. Hierarchical relationships within the H.
      pusillum clade are poorly resolved by the ITS data, but the rps16 intron
      sequences form two well-supported clades which are geographically, rather than
      taxonomically, correlated. A similar geographical structure is found in the ITS
      data, when analyzed with the NeighbourNet method. The apparent rate of change
      within Heliosperma is slightly higher for rps16 as compared to ITS. In contrast,
      in the Sileneae outgroup, ITS substitution rates are more than twice as high as
      those for rps16, a situation more in agreement with what has been found in other
      rate comparisons of noncoding cpDNA and ITS. Unlike most other Sileneae ITS
      sequences, the H. pusillum group sequences display extensive polymorphism. A
      possible explanation to these patterns is extensive hybridization and gene flow
      within Heliosperma, which together with concerted evolution may have eradicated
      the ancient divergence suggested by the rps16 data. The morphological
      differentiation into high elevation, mainly widely distributed taxa, and low
      elevation narrow endemics is not correlated with the molecular data, and is
      possibly a result of ecological differentiation.

PMID- 17188522
TI  - Stable expression of adenylyl cyclase 2 leads to the functional rescue of human 5
      HT6 receptor in a CHODUKX cell line.
AB  - INTRODUCTION: The generation and selection of recombinant cell lines specifically
      designed to express high picomolar levels of heterologous G-protein-coupled
      receptors can lead to loss of ligand-dependent functional activity. As a result,
      the clonal selection of a suitable host model and/or lower receptor expression
      levels within the same cell system becomes important especially when a functional
      assay is necessary to evaluate the pharmacological potencies of ligands at the
      receptor site. To address this question, we examined the utility of various
      signal transducers to restore the functional capacity of a high expressing human
      5-HT(6) receptor CHODUKX system. METHODS: The plasmids for human 5-HT(6) receptor
      and full-length human G(s), G(olf) and rat adenylyl cyclase isoforms 2 (rAC2) and
      5 were obtained by PCR. The h5-HT(6) receptor pHTop plasmid was stably
      transfected into a CHODUKX cell line to generate an h5-HT(6) expressing clone. h5
      HT(6) CHODUKX cells were transfected with signaling components and functional
      cAMP responses measured. rAC2 was selected to generate a double stable h5-HT(6)
      receptor/rAC2 pHTop CHODUKX line. RESULTS: The h5-HT(6) receptor CHODUKX line was
      a high receptor expressor (>2 pmol/mg protein) but an extremely poor ligand
      dependent functional responder, failing to produce the appropriate cAMP signal
      upon addition of selective agonists. We found that stable co-expression of rAC2
      with h5-HT(6) receptor in the CHODUKX cell line displayed dose-dependent cAMP
      accumulation following agonist treatment. The pharmacological profile of several
      agonists in the h5-HT(6) receptor/rAC2 cell line was consistent with an h5-HT(6)
      like receptor-mediated event. DISCUSSION: We provide evidence for restoration of
      functional capacity in a heterologous G(s)-coupled 5-HT(6)/AC2 CHODUKX expression
      system. We discuss the broader value of a stable AC2-expressing CHODUKX cell line
      in which the generation of high expressing GPCR receptor/AC2 lines can retain
      their functional responsiveness and provide pharmacological drug comparisons
      between the same host line for screening purposes and measurement of multiple
      cellular parameters.

PMID- 17188524
TI  - Arthroscopic estimation of the extent of chondropathy.
AB  - INTRODUCTION: Arthroscopy has been used to evaluate articular cartilage (AC)
      pathology in osteoarthritis (OA) for outcome measurement and validation of non
      invasive imaging. However, many fundamental aspects of arthroscopic assessment
      remain un-validated. OBJECTIVES: This study evaluated arthroscopic estimates of
      extent of chondropathy. METHODS: Serial arthroscopic assessments were performed
      in a group of 15 sheep before and after bilateral stifle medial meniscectomy
      (MMx). Post-mortem assessments were performed in un-MMx sheep and 4 and 16 weeks
      post-MMx. Arthroscopic assessments of the extent of each grade of chondropathy
      were compared with a non-arthroscopic hybrid assessment that incorporated
      biomechanical, thickness and macroscopic assessments. RESULTS: Arthroscopy
      evaluated only 36% of AC and missed significant pathological changes, softening
      and chondro-osteophyte, occurring in peripheral regions. The patterns of change
      in arthroscopic assessments were similar to those of the non-arthroscopic
      assessment but there was a very strong tendency to over-estimate the extent of
      softened AC after MMx. In spite of these limitations arthroscopic assessments
      were responsive to change. Estimates of the extent of normal and softened AC were
      most responsive to change over time followed by estimates of superficial and deep
      fibrillation. Arthroscopy was as an excellent discriminator between normal and
      OA. Assessments of chondro-osteophyte and exposed bone were not responsive to
      change. CONCLUSIONS: Arthroscopic estimates of extent of chondropathy are prone
      to substantial error. While experience and training may reduce these errors other
      approaches may more effectively improve performance.

PMID- 17188523
TI  - In vitro effects of non-steroidal anti-inflammatory drugs on cytokine, prostanoid
      and matrix metalloproteinase production by interface membranes from loose hip or
      knee endoprostheses.
AB  - OBJECTIVE: To study the effects of the non-steroidal anti-inflammatory drugs
      (NSAIDs) aceclofenac, piroxicam, tenoxicam and indomethacin on cytokine, matrix
      metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and
      prostaglandin E2 (PGE2) production, by interface membranes (IFT), obtained at
      revision surgery for aseptic loosening of total joint arthroplasty. Involvement
      of these soluble factors is well documented and probably, a pharmaceutically
      induced inhibition of them might retard loosening. METHODS: IFTs from 10 patients
      with a loose hip or knee endoprosthesis were collected. The possibility of septic
      loosening was thoroughly excluded by histopathologic and microbiologic
      evaluation. IFTs were cultured in the absence or presence of the tested drugs and
      the levels of the soluble mediators were determined, using electrophoretic and
      enzyme-linked immunosorbent assay techniques. Paracetamol was used as neutral
      drug. RESULTS: All NSAIDs exhibited a pronounced inhibitory effect upon the
      production of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha).
      This specific effect on IL-6 is reported in the literature for the first time.
      The majority of NSAIDs also induced the production of IL-1beta in an adequate
      portion of samples. These drugs did not have a clear effect on MMP synthesis, but
      they had a stimulatory tendency on TIMP-1 production. Paracetamol, significantly
      decreased the synthesis of TNF-alpha and that of the gelatinases. CONCLUSION: Our
      in vitro results are encouraging, since it appears that the action of NSAIDs,
      globally considered, may be beneficial upon the loosening process. The inhibitory
      effect of paracetamol upon TNF-alpha and gelatinases is intriguing. Our data, if
      supported by similar observations, probably justify performance of long-term
      clinical trials.

PMID- 17188525
TI  - Novel fast semi-automated software to segment cartilage for knee MR acquisitions.
AB  - OBJECTIVE: Validation of a new fast software technique to segment the cartilage
      on knee magnetic resonance (MR) acquisitions. Large studies of knee
      osteoarthritis (OA) will require fast and reproducible methods to quantify
      cartilage changes for knee MR data. In this report we document and measure the
      reproducibility and reader time of a software-based technique to quantify the
      volume and thickness of articular cartilage on knee MR images. METHODS: The
      software was tested on a set of duplicate sagittal three-dimensional (3D) dual
      echo steady state (DESS) acquisitions from 15 (8 OA, 7 normal) subjects. The
      repositioning, inter-reader, and intra-reader reproducibility of the cartilage
      volume (VC) and thickness (ThC) were measured independently as well as the reader
      time for each cartilage plate. The root-mean square coefficient of variation
      (RMSCoV) was used as metric to quantify the reproducibility of VC and mean ThC.
      RESULTS: The repositioning RMSCoV was as follows: VC=2.0% and ThC=1.2% (femur),
      VC=2.9% and ThC=1.6% (medial tibial plateau), VC=5.5% and ThC=2.4% (lateral
      tibial plateau), and VC=4.6% and ThC=2.3% (patella). RMSCoV values were higher
      for the inter-reader reproducibility (VC: 2.5-8.6%) (ThC: 1.9-5.2%) and lower for
      the intra-reader reproducibility (VC: 1.6-2.5%) (ThC: 1.2-1.9%). The method
      required an average of 75.4min per knee. CONCLUSIONS: We have documented a fast
      reproducible semi-automated software method to segment articular cartilage on
      knee MR acquisitions.

PMID- 17188526
TI  - Experimental alcoholism and pathogenesis of prostatic diseases in UChB rats.
AB  - Previous studies have shown that long-term alcohol treatment has negative effects
      on prostatic stromal-epithelial interaction. Thus, the aim of the present study
      was to analyze the histochemical, immunohistochemical and ultrastructural
      alterations that occur in the prostatic stroma and epithelium of rats submitted
      to chronic alcohol ingestion and alcohol abstinence, as well as to establish the
      relationship between these changes and prostatic diseases. Thirty male rats (10
      Wistar and 20 UChB rats) were divided into three experimental groups: the control
      group received tap water, the alcoholic group received ethanol diluted to 10
      degrees G.L. for 150 days, and the abstinent group received the same liquid diet
      as the alcoholic group up to 120 days of treatment and only tap water for 30 days
      thereafter. At the end of treatment, all animals were sacrificed and the ventral
      lobe of the prostate was removed and processed for histochemical,
      immunohistochemical and ultrastructural analyses. In addition, plasma
      testosterone levels were measured. The results showed prostatic intraepithelial
      neoplasia, infolding of the epithelium towards the stroma, stromal hypertrophy
      and the presence of inflammatory cells in alcoholic animals. In the abstinent
      group, alterations were noted mainly in the stromal area. In conclusion, ethanol
      triggers alterations in prostatic epithelial and stromal compartments, affecting
      the stromal microenvironment and predisposing the organ to pathological
      processes.

PMID- 17188527
TI  - Analysis of ghost cells in calcifying cystic odontogenic tumors by confocal laser
      scanning microscopy.
AB  - OBJECTIVE: The confocal laser scanning microscope represents an effective tool
      for studying biological samples stained for fluorescence observation. In this
      study we have used the confocal microscope to analyze ghost cells in calcifying
      cystic odontogenic tumors. STUDY DESIGN: Specimens from 15 calcifying cystic
      odontogenic tumor cases were stained with hematoxylin and eosin, and scanned by a
      confocal laser scanning microscope to generate optically sectioned images.
      RESULTS: All of the analyzed samples presented autofluorescent cells that were
      identified as ghost cells. The degree of autofluorescence intensity was variable
      and may be a result of the presence of hard keratin. CONCLUSION: The confocal
      laser scanning microscope may be of help in analyzing and defining the nature and
      extent of keratinization processes in calcifying cystic odontogenic tumor ghost
      cells.

PMID- 17188528
TI  - In vitro assessment of cone beam local computed tomography for proximal caries
      detection.
AB  - OBJECTIVES: To compare the accuracy of local computed tomography (LCT) and
      conventional radiography for proximal caries detection and depth assessment.
      STUDY DESIGN: An in vitro model was used consisting of 20 extracted posterior
      teeth with 18 caries lesions. Local computed tomography slices were reconstructed
      in axial and parasagittal planes from 100 basis projections. Conventional
      radiographs were also acquired. Eight observers determined the presence and depth
      of caries lesions. Receiver operating characteristic analysis and weighted kappa
      statistics were used. RESULTS: Local computed tomography had a mean A(z) score of
      0.82 (SD = 0.07) and conventional radiography of 0.79 (SD = 0.08; analysis of
      variance: P > .05). Interobserver agreement was moderate. The mean kappa for
      depth assessment was 0.68 (SD = 0.06) for LCT and 0.47 (SD = 0.08) for
      conventional radiography (analysis of variance: P < .05). Local computed
      tomography resulted in substantial and conventional radiography in moderate
      interobserver agreement. CONCLUSIONS: There is no difference between LCT and
      conventional radiography for proximal caries detection. Local computed tomography
      was more accurate for assessing caries lesion depth.

PMID- 17188529
TI  - Danish practitioners' assessment of factors influencing the outcome of endodontic
      treatment.
AB  - OBJECTIVE: This investigation explored the hypothesis that among general dental
      practitioners (GDPs), the performance of root fillings of substandard quality
      might be associated with deficient knowledge of factors important to the outcome
      of endodontic treatment. STUDY DESIGN: A questionnaire was mailed to 600 randomly
      selected GDPs. The influence of 24 factors on treatment outcome was assessed on
      100 mm visual analog scales. A gold standard (GS) was established by an external
      group of researchers. Comparisons between the GDP response and the GS were
      analyzed using Wilcoxon tests. RESULTS: Despite large variation, the responses
      were significantly associated with sex, year of education, and exposure to
      endodontic treatment. Compared with the GS, the GDPs emphasized factors
      associated with clinical symptoms and underevaluated factors related to the
      microbial situation in the root canal. CONCLUSIONS: The GDPs seemed to regard
      endodontics mainly to be a procedure to keep a patient free of symptoms.

PMID- 17188530
TI  - Dental management of a patient with takotsubo cardiomyopathy: a case report.
AB  - Takotsubo cardiomyopathy (TCM) is a relatively new concept in cardiovascular
      disease. The clinical symptoms of TCM are similar to those of a myocardial
      infarction, but both the mechanism and the management of TCM are different from
      those of myocardial infarction. The cause of TCM is unclear, but it is suggested
      to occur in conjunction with excessive circulating catecholamines due to stress.
      Thus, control of the stress reaction and restriction of catecholamine levels are
      considered important for prevent of TCM onset. We report the dental management of
      a patient with intellectual disability who had anamnesis of TCM and
      cardiopulmonary arrest under restraint during a previous dental appointment in
      another dental clinic. We used intravenous sedation with both midazolam and
      propofol, by which the excessive hormonal reaction that caused TCM onset and
      cardiopulmonary arrest was controlled, for dental treatment in our facility. All
      planned dental treatment was then performed without any problems.

PMID- 17188531
TI  - In vitro assessment of local computed tomography for the detection of
      longitudinal tooth fractures.
AB  - OBJECTIVE: To test the accuracy of local computed tomography (LCT) in detecting
      longitudinal fractures in comparison with conventional periapical radiographs.
      STUDY DESIGN: Longitudinal fractures were induced in 30 of 60 teeth. The teeth
      were placed in a dry dentate mandible with soft tissue simulation. A laboratory
      LCT unit was used to acquire 180 basis projections with 1 degree separation along
      a 180 degree arc. Conventional radiographs served as the control modality.
      Correlated axial, coronal, and sagittal views were presented to 10 observers. The
      observers determined the presence of a root fracture by using a 5-point receiver
      operating characteristic confidence scale. RESULTS: The mean A(z) for LCT was
      0.91 (SD = 0.07). The mean A(z) for conventional radiography was 0.70 (SD =
      0.07). The difference between the modalities was statistically significant
      (analysis of variance: P < .0002), whereas the differences between the observers
      was not (analysis of variance: P = .319). CONCLUSION: Local CT significantly
      improves the detection of longitudinal fractures in vitro compared with
      conventional periapical radiography.

PMID- 17188532
TI  - Accuracy of the apex locating function of TCM Endo V in simulated conditions: a
      comparison study.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of the apex
      locating function of the TCM Endo V and to compare the results to these of the
      Root ZX. STUDY DESIGN: Forty-seven extracted maxillary incisor teeth with mature
      apices and patent single root canals were used for the study. After the root
      surfaces were cleaned and access cavities were prepared, the true working lengths
      (TL) were determined with a #10 stainless steel file. All samples were mounted in
      an alginate model especially developed to test the apex locators. Both electronic
      apex locators were used according to the manufacturer's recommendations and
      adjusted to 0.5-mm accuracy to the apical foramen. EL(1) was designates as the
      working length measured with Root ZX and EL(2) was designated as the working
      length measured with TCM Endo V. A paired t test was used to statistically
      analyze the significance of the mean differences at the 95% confidence interval
      of the differences (P = .001) among TL, EL(1), and EL(2). RESULTS: There were no
      statistically significant differences between TL and EL(1), TL and EL(2), and
      EL(1) and EL(2) (P = .001). Both Root ZX and TCM Endo V gave similar results.
      CONCLUSIONS: TCM Endo V proved to be as reliable as Root ZX but the use of the
      device to determine the working length was not easy as Root ZX. Further studies
      are needed to compare TCM Endo V in clinical conditions with similar electric
      motor and apex locator combined devices.

PMID- 17188533
TI  - Full-length cDNA cloning and protein three-dimensional structure modeling of
      porcine prothrombin.
AB  - Prothrombin is a vitamin K-dependent serine protease and plays pivotal roles in
      both procoagulant and anticoagulant pathway of hemostasis. In this study, we
      cloned the full-length cDNA of porcine prothrombin by cDNA library screening and
      SMART RACE technique. The full-length cDNA is 2027 bp, with a 1869 bp Open
      Reading Frame (ORF) coding 623 amino acids. The deduced protein of porcine
      prothrombin contains signal peptide, propeptide, Gla domain, two kringle domains
      and trypsin domain. Porcine prothrombin shares 86.15% nucleotide similarity and
      83% amino acid similarity with human prothrombin. The trypsin domain is highly
      conserved between the two species with 92.1% amino acid identity. Macromolecular
      interaction sites comparison between porcine and human prothrombin suggests that
      the Gla domain in porcine prothrombin contains an additional potential gamma
      carboxyglutamic acid site. However, a thrombin cleavage site (Arg284-Thr285) in
      its light chain is lost. When thrombin heavy chain is concerned, the most
      important functional sites such as catalytic triad DHS, RGD site, Na+ binding
      site and anion-binding exosite-I and II are highly conserved. However, great
      differences have been observed between residues 145 and 158 of heavy chain which
      is associated with thrombomodulin binding. Two important limited proteolysis
      sites at Ala150 and Lys154 were lost in porcine sequence, which would affect
      epsilon-thrombin and gammaT-thrombin generation. Comparison on 3-D protein models
      demonstrates that these proteins are obviously different in autolysis loop
      (Lys145 to Gly155). Compared with that of human prothrombin, variation at
      critical recognition sites would likely alter its binding affinity and reaction
      velocity, which would contribute to coagulation disorder when porcine liver is
      transplanted into human body.

PMID- 17188534
TI  - A new RNA branching activity: the GIR1 ribozyme.
AB  - The formation of lariat intermediates during the first step of splicing of group
      II introns and spliceosomal introns is a well-studied fundamental reaction in
      molecular biology. Apart from this prominent example, there are surprisingly few
      occurrences of branched nucleotides or even 2',5'-phosphodiester bonds in
      biology. We recently described a new ribozyme, the GIR1 branching ribozyme, which
      catalyzes the formation of a tiny lariat that caps an mRNA. This new example
      together with work on artificial branching ribozymes and deoxyribozymes shows
      that branching is facile and points to the possibility that branching reactions
      could be more prevalent than previously recognized.

PMID- 17188535
TI  - Phenotypic characterization and in vitro antifungal sensitivity of Candida spp.
      and Malassezia pachydermatis strains from dogs.
AB  - Yeasts of the genera Candida and Malassezia can be found as commensal
      microorganisms in animals. The main species of importance in veterinary medicine
      are Malassezia pachydermatis and Candida albicans. The objectives of this study
      were to conduct a phenotypic characterization and to evaluate the in vitro
      antifungal sensitivity of strains of C. albicans (n=5), C. tropicalis (n=3) and
      M. pachydermatis (n=32) isolated from dogs. The phenotyping was based on macro
      and micromorphological features as well as biochemical analysis. The techniques
      of microdilution in broth and dilution in agar were used to evaluate the in vitro
      sensitivity of Candida spp. and M. pachydermatis, respectively. The tested drugs
      were ketoconazole (KTC), itraconazole (ITC), fluconazole (FLC) and amphotericin B
      (AMB). The morphological analysis of the strains of Candida spp. and M.
      pachydermatis did not show any noteworthy alterations when compared to standard
      strains. On the other hand, in the biochemical tests, 34.4% of the strains of M.
      pachydermatis were negative for the urease test. Four strains of C. albicans were
      resistant to FLC with a minimum inhibitory concentration (MIC) >64microg/mL and
      all were resistant to KTC and ITC (MIC>16microg/mL). The MIC for two strains of
      C. tropicalis were >16microg/mL for KTC and ITC, and >64microg/mL for FLC. It is
      worth highlighting that all of the strains tested were sensitive to AMB with the
      MIC varying from 0.25-1.0microg/mL. All strains of M. pachydermatis were
      sensitive to ITC with a minimum fungistatic concentration (MFC) 0.0075microg/mL.
      The MIC for 29 strains was the same (MFC0.0075microg/mL) for KTC. The MFCs for
      FLC varied from 1 to 16microg/mL, and for AMB, the MFC interval was 0.125
      8microg/mL. There were no alterations in the classic phenotypic features of the
      strains of Candida spp. and M. pachydermatis isolated from dogs but, unlike M.
      pachydermatis, Candida spp. were much more resistant to azole antifungal agents.

PMID- 17188536
TI  - Globin genes transcriptional switching, chromatin structure and linked lessons to
      epigenetics in cancer: a comparative overview.
AB  - At the present time research situates differential regulation of gene expression
      in an increasingly complex scenario based on interplay between genetic and
      epigenetic information networks, which need to be highly coordinated. Here we
      describe in a comparative way relevant concepts and models derived from studies
      on the chicken alpha- and beta-globin group of genes. We discuss models for
      globin switching and mechanisms for coordinated transcriptional activation. A
      comparative overview of globin genes chromatin structure, based on their genomic
      domain organization and epigenetic components is presented. We argue that the
      results of those studies and their integrative interpretation may contribute to
      our understanding of epigenetic abnormalities, from beta-thalassemias to human
      cancer. Finally we discuss the interdependency of genetic-epigenetic components
      and the need of their mutual consideration in order to visualize the regulation
      of gene expression in a more natural context and consequently better understand
      cell differentiation, development and cancer.

PMID- 17188537
TI  - Exercise warms adult leatherback turtles.
AB  - Leatherback sea turtles (Dermochelys coriacea) can maintain body temperature
      (T(B)) up to 18 degrees C above that of the surrounding sea water (T(W)) which
      allows leatherbacks to enter cold temperate waters and have the largest global
      range of any reptile. Using a cylindrical model of a leatherback we investigated
      the extent to which heat production through variation of swim speed could be used
      in a leatherback's thermal strategy. Drag force of a full scale cast of a
      leatherback was measured in a low velocity wind tunnel to obtain an estimate of
      the metabolic cost needed to offset drag. Heat released in the core of a turtle
      as a byproduct of the metabolic cost of locomotion is conducted from the core of
      the turtle to the surrounding water through its insulation layer. By keeping
      insulation thickness constant, we highlight the effectiveness of swim speed in
      maintaining T(B)-T(W). Our model, when tested against published data at a given
      T(W), showed a close correlation between predicted and measured swimming speed at
      a given T(B). We conclude that the ability to maintain a large T(B)-T(W) is an
      interplay between mass, insulation thickness and water temperature selection but
      behavioural control of swimming speed predominates.

PMID- 17188538
TI  - Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese
      population.
AB  - Deficient activity of the Dihydropteridine Reductase enzyme (DHPR; EC 1.5.1.34;
      OMIM 261630) is due to mutations in the Quinoid Dihydropteridine Reductase gene
      on 4p15.3 (QDPR; RefSeq NM_000320). It results in defective recycling of
      tetrahydrobiopterin (BH(4)) and homozygotes have a rare form of atypical
      Hyperphenylalaninaemia and Phenylketonuria (aPKU). The heterozygote frequency in
      the Maltese population is high at 3.3%. The more recently described and rarer
      type of BH(4) deficiency due to Sepiapterin Reductase enzyme deficiency (SR; EC
      1.1.1.153; OMIM 182125), which presents as an atypical form of Dopa Responsive
      Dystonia (DRD) [L. Bonafe, B. Thony, J.M. Penzien, B. Czarnecki, N. Blau,
      Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin
      dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia,
      Am. J. Hum. Genet. 69 (2001) 269-277; B.R.G. Neville, R. Parascandalo, S. Attard
      Montalto, R. Farrugia, A.E. Felice, A congenital dopa responsive motor disorder:
      a Maltese variant due to sepiapterin reductase deficiency, Brain 128 (Pt10)
      (2005) 2291-2296.] has also been identified at high frequency (4.6%) in this
      population. Two mutations, the c.68G>A in QDPR (p.G23D), and the new SPR, IVS2
      2A>G mutation at the splice site consensus sequence in intron 2 of the
      Sepiapterin Reductase gene (SPR; RefSeq NM_003124) on 2p14-p12, were found to be
      the sole causative mutations in all the patients with DHPR deficiency and SR
      deficiency studied. All parents were heterozygotes for the corresponding mutation
      and showed no clinical symptoms. Three polymorphisms, c.96C>T (p.A32A), c. 345G>A
      (p.S115S) and c. 396G>A (p.L132L), have also been identified in the QDPR gene,
      defining four wild-type frameworks, useful in molecular epidemiology studies. The
      c. 68G>A mutation in QDPR was found only on framework I, suggesting a founder
      effect. In contrast no additional sequence diversity was found in the SPR gene
      whether in wild-type or mutant alleles which is also consistent with a founder
      effect.

PMID- 17188540
TI  - [Transfusion risk analysis with regard to vCJD in France].
AB  - The latest updates (February 2004 and February 2005) of the analysis of the risk
      of transmission of the agent of Creutzfeldt-Jakob disease (CJD) by blood and
      blood products in France firstly reported in 2000, were triggered by the two
      cases of probable transmission of variant CJD (vCJD) by transfusion reported in
      the UK, and the notification of two French cases of vCJD who had been blood
      donors on several occasions before clinical onset. Even though some figures of
      the quantitative assumption used in the risk analysis have been modified since
      2000, the conclusion as regards the risk for blood cellular component is
      considered unchanged: it can be assumed that one unit of labile blood products
      will contain more than one infectious unit if the donor is incubating the
      disease. Therefore, the residual risk of receiving by transfusion one infectious
      blood unit is depending on the prevalence of subjects incubating the disease in
      the blood donor population. For this particular aspect, the expected number of
      clinical vCJD cases to occur in France has been lowered since 2000. However, the
      worst-case scenario of 300 cases in the next 60 years has been maintained in the
      risk analysis, leading to the hypothesis that one blood donor per 120,000 could
      be infectious. In conclusion, the risk of getting one infectious blood unit is
      considered probable to a level of 1/120,000, but the benefit outweighs the risk
      if the use of transfusion is restricted to well justified indications and if
      patients are informed a priori and a posteriori.

PMID- 17188542
TI  - Mechanisms of transfusion-linked parasite infection.
AB  - Besides bacteriae and viruses, parasite infections can be transmitted by blood as
      a consequence of blood transfusion. To be transmitted by blood transfusion,
      parasites must: -i) circulate in the blood stream of donors, -ii) comprise of
      certain physical characteristics and resist processing steps leading to the
      preparation of labile blood products (packed red blood cells, therapeutic frozen
      plasma, or platelet concentrates), -iii) survive conservation; further, to
      generate infection in the blood receiver, such parasites must retain infectivity.
      In this Forum, the main characteristics of parasites-with respect to
      transmissibility by blood exposure-are recalled. This forum will further discuss
      each of these topics and try to make an issue with possible risks in transfusion,
      in countries that are either non-endemic for the given parasite or which can
      afford implementation of preventive measures.

PMID- 17188541
TI  - vCJD and blood transfusion in the United Kingdom.
AB  - A study was set up in the UK in 1997 to examine whether there is any evidence
      that variant Creutzfeldt-Jakob disease (vCJD) is transmitted by blood
      transfusion. To date, the study has identified three probable cases of vCJD
      transmission by blood transfusion, including two clinical cases and one pre- (or
      sub-) clinical case.

PMID- 17188539
TI  - Cellular and tissue distribution of intravenously administered agalsidase alfa.
AB  - alpha-Galactosidase A is the lysosomal hydrolase that is deficient in patients
      with Fabry disease. Intravenous infusion of agalsidase alfa, a preparation of
      alpha-Galactosidase A, is used for enzyme replacement therapy (ERT) in patients
      with Fabry disease. Although ERT appears to show some beneficial effects, most
      patients show only a modest response. We investigated using immunohistochemistry
      the relative tissue and cellular distribution of agalsidase alfa after a single
      intravenous injection in a mouse knockout model of Fabry disease. Specific
      immunostaining for agalsidase alfa was found only in liver, kidney, heart,
      testes, adrenal gland, spleen and bone marrow. There was no difference in
      distribution of the infused enzyme distribution among tissues sampled 4, 24, and
      48h post-injection. The intracellular localization of immunopositivity varied
      considerably between organs with vascular endothelium being the most commonly
      positive site. alpha-Galactosidase A specific activity in tissue homogenates
      matched the relative extent of agalsidase alfa immunostaining distribution in the
      same organs. We conclude that intravenously injected agalsidase alfa has a very
      heterogeneous systemic distribution using an immunostaining technique.

PMID- 17188543
TI  - vCJD and blood transfusion: risk assessment in the United Kingdom.
AB  - The risk of vCJD transmission via blood transfusion depends on potential levels
      of infectivity, recipients' exposure to infected donors and individual
      susceptibility. On infectivity, SEAC (the UK's main scientific advisory committee
      on TSEs), has published an updated position statement. Based on animal models,
      this suggests that infectivity is split roughly equally between leucocytes and
      plasma, with negligible levels directly associated with red cells or platelets.
      Risk assessments are now therefore based on the amounts of plasma and leucocytes
      within each component as transfused. Recipients' exposure to infection depends
      critically on the prevalence of infection in the population. This remains
      unknown, so a range of assumptions must still be considered. A further
      consideration is the likelihood of any infected donors' blood being infective.
      Those infected in the primary outbreak will now have been incubating vCJD for 10
      25 years. Current thinking is that blood may be more infective later in the
      incubation period. This reinforces the case for a precautionary approach to
      transmission risks, despite the small number of incidents seen so far. Exposure
      will also depend on how many donors contributed components to a given individual.
      Recent work has shown that more patients receive large numbers of units than
      previously thought. These highly-transfused patients are a particular cause for
      concern. The current precautionary assumption is of all recipients being
      susceptible to infection by transfusion, though incubation periods may differ
      markedly.

PMID- 17188544
TI  - [vCJD epidemiology in France].
AB  - Variant Creutzfeldt-Jakob disease (vCJD) is the only form of prion diseases
      linked to bovine spongiform encephalopathy (BSE). The disease was first described
      in the United-Kingdom (UK) and France is the second affected country with 21
      cases. Clinical, genetic and neuropathological features are the same in both
      countries. Comparison of the total number of cases in France and in the UK,
      according to dates of onset, shows that, in France, the maximum incidence seems
      to be five years delayed and that, in the UK, the number of vCJD cases regularly
      decreases since 1999. Delayed exposure to contaminated beef products in France
      compared to the UK could explain this temporal gap. Three cases of vCJD after
      transfusion of labile blood products were observed in the UK. No such of cases
      were observed in France but three patients developing signs of vCJD in 2004 were
      blood donors. A total of 42 recipients were identified with 17 recipients still
      alive.

PMID- 17188545
TI  - [Ovarian and peritoneal sarcoidosis mimicking an ovarian cancer].
AB  - Ovarian and peritoneal sarcoidosis is a very rare condition, with an atypical
      clinical presentation close to that of ovarian cancer. An erroneous diagnosis
      could induce a definitive castration. A 38-year-old woman was admitted because of
      ascites and weight loss. A computerized tomography scan revealed multiple soft
      tissue nodules in the pelvis, on the ovaries as well as peritoneal deposits.
      Histological examination after laparoscopic biopsy was indicative of sarcoidosis.
      Corticosteroids were given to the patient and the symptoms quickly subsided. This
      case with its clinical presentation is discussed in comparison with previously
      reported cases.

PMID- 17188546
TI  - [Radiologically-guided hysterosalpingography and tubal catheterization].
AB  - Radiological exploration of hypofertility by means of hysterosalpingography is a
      method still valid but no longer sufficient. Tubal catheterization has thus
      become a necessary complementary exam in order to eliminate the pseudo
      obturations of hysterosalpingography and, in case of proximal tubal obstructions,
      to obtain pregnancies. The conditions for the realization of hysteroalpingography
      and tubal catheterization are hereby described, with emphasis on the rigorous
      technique that is required together with careful listening to the patients.

PMID- 17188547
TI  - McKenzie classification of mechanical spinal pain: profile of syndromes and
      directions of preference.
AB  - The purpose of this study was to develop a profile of the use of McKenzie
      classifications of diagnosis and treatment, by physiotherapists credentialed in
      the McKenzie method in New Zealand. This system has been in common use for more
      than 20 years and the inter-rater reliability of the assessment has been
      previously established for therapists at this level of training. Prior studies
      identifying the classification of patients according to syndrome and directional
      preference have been mainly for the lumbar spine. The 34 participants for this
      study each assessed and classified 10 consecutive spinal patients during a 10
      week period. Of the 340 patients assessed, 19 were excluded. Of those with pain
      arising from the lumbar spine; 140/187 were classified as reducible derangement
      syndrome, 11/187 were classified as irreducible derangement, 11/187 as
      dysfunction syndrome, 1/187 as posture syndrome and 24/187 as 'other'. For
      treatment in the reducible derangement syndrome; 98/140 were given extension,
      8/140 were given flexion and 34/140 were given lateral movements of either side
      gliding or rotation. Classifications and treatment for the cervical and thoracic
      spine groups followed similar patterns. These findings add to the external
      validity of the McKenzie method, and support mechanical evaluation of spinal
      patients according to directional preference.

PMID- 17188548
TI  - What is the effect of taping along or across a muscle on motoneurone
      excitability? A study using triceps surae.
AB  - Taping along the skin overlying lower trapezius reduces motoneurone excitability
      in healthy subjects [Alexander, C.M., Stynes, S., Thomas, A., Lewis, J., Harison,
      P.J., 2003. Does tape facilitate or inhibit the lower fibres of trapezius? Manual
      Therapy 8, 37-41]. It remains unclear whether this effect is: (a) specific to
      trapezius and (b) specific to the direction of application of the tape. In light
      of this, the excitability of another muscle was measured in order to see if these
      results were repeatable and independent of the muscle taped. Thus, the
      excitability of the medial and lateral gastrocnemius (MG and LG) and soleus (Sol)
      motoneurone pool was assessed using the Hoffman reflex (H reflex). The amplitude
      of this reflex was measured with the tape aligned across and then along the
      direction of the MG muscle fibres. Tape aligned across the fibres failed to
      affect motoneurone excitability (MG P=0.61, LG P=0.69, Sol P=0.17). Under tape
      and sports tape applied together aligned along the MG muscle reduced the
      excitability of both MG and LG (19% (P=0.01) and 13% (P=0.01), respectively).
      These observations suggest that any change to movement patterns with tape
      application cannot be explained by facilitation of the motoneurone excitability.

PMID- 17188549
TI  - Lim kinases, regulators of actin dynamics.
AB  - The members of the LIM kinase (LIMK) family, which include LIMK 1 and 2, are
      serine protein kinases involved in the regulation of actin polymerisation and
      microtubule disassembly. Their activity is regulated by phosphorylation of a
      threonine residue within the activation loop of the kinase by p21-activated
      kinases 1 and 4 and by Rho kinase. LIMKs phosphorylate and inactivate the actin
      depolymerising factors ADF/cofilin resulting in net increase in the cellular
      filamentous actin. Hsp90 regulates the levels of the LIM kinase proteins by
      promoting their homo-dimerisation and trans-phosphorylation. Rnf6 is an E3
      ubiquitin ligase responsible for LIMK degradation in neurons. The activity of
      LIMK1 is also required for microtubule disassembly in endothelial cells. While
      LIMK1 localizes mainly at focal adhesions, LIMK2 is found in cytoplasmic punctae,
      suggesting that they may have different cellular functions. LIMK1 was shown to be
      involved in cancer metastasis, while LIMK2 activation promotes cells cycle
      progression.

PMID- 17188550
TI  - Current perspectives on NMDA-type glutamate signalling in bone.
AB  - Bone is a complex, evolving tissue, architecturally defined by the activities of
      osteoclasts and osteoblasts that continually resorb and replace the mineralised
      matrix. Numerous regulatory mechanisms exist to control bone remodelling and the
      maintenance of bone mass. The consequences of inappropriate or uncoupled bone
      resorption and formation are significant and invariably lead to different disease
      states, the most prevalent being osteoporosis. In recent years, much attention
      has focused on unravelling the systemic and local signalling interactions that
      influence the differentiation and function of bone cells with a view to
      developing our understanding of bone biology and identifying potential new
      targets for therapeutic intervention. Several lines of evidence indicate that
      neurotransmitters and neuromodulators have influential roles to play in the
      regulation of bone remodelling and much of this research has involved analysis of
      the excitatory amino acid glutamate. This review will summarise current
      understanding of glutamate signalling in bone cells, addressing specifically the
      function of N-methyl-D-aspartate (NMDA)-type glutamate receptor signalling
      mechanisms, and will address the functional significance and future prospects for
      this area of research.

PMID- 17188551
TI  - Estimation of the 3D self-similarity parameter of trabecular bone from its 2D
      projection.
AB  - It has been shown that the analysis of two dimensional (2D) bone X-ray images
      based on the fractional Brownian motion (fBm) model is a good indicator for
      quantifying alterations in the three dimensional (3D) bone micro-architecture.
      However, this 2D measurement is not a direct assessment of the 3D bone
      properties. In this paper, we first show that S(3D), the self-similarity
      parameter of 3D fBm, is linked to S(2D), that of its 2D projection, by
      S(3D)=S(2D)-0.5. In the light of this theoretical result, we have experimentally
      examined whether this relation holds for trabecular bone. Twenty one specimens of
      trabecular bone were derived from frozen human femoral heads. They were digitized
      using a high resolution mu-CT. Their projections were simulated numerically by
      summing the data in the three orthogonal directions and both 3D and 2D self
      similarity parameters were measured. Results show that the self-similarity of the
      3D bone volumes and that of their projections are linked by the previous
      equation. This demonstrates that a simple projection provides 3D information
      about the bone structure. This information can be a valuable adjunct to the bone
      mineral density for the early diagnosis of osteoporosis.

PMID- 17188552
TI  - Universal dimensions of social cognition: warmth and competence.
AB  - Like all perception, social perception reflects evolutionary pressures. In
      encounters with conspecifics, social animals must determine, immediately, whether
      the "other" is friend or foe (i.e. intends good or ill) and, then, whether the
      "other" has the ability to enact those intentions. New data confirm these two
      universal dimensions of social cognition: warmth and competence. Promoting
      survival, these dimensions provide fundamental social structural answers about
      competition and status. People perceived as warm and competent elicit uniformly
      positive emotions and behavior, whereas those perceived as lacking warmth and
      competence elicit uniform negativity. People classified as high on one dimension
      and low on the other elicit predictable, ambivalent affective and behavioral
      reactions. These universal dimensions explain both interpersonal and intergroup
      social cognition.

PMID- 17188553
TI  - Questioning the social intelligence hypothesis.
AB  - The social intelligence hypothesis posits that complex cognition and enlarged
      "executive brains" evolved in response to challenges that are associated with
      social complexity. This hypothesis has been well supported, but some recent data
      are inconsistent with its predictions. It is becoming increasingly clear that
      multiple selective agents, and non-selective constraints, must have acted to
      shape cognitive abilities in humans and other animals. The task now is to develop
      a larger theoretical framework that takes into account both inter-specific
      differences and similarities in cognition. This new framework should facilitate
      consideration of how selection pressures that are associated with sociality
      interact with those that are imposed by non-social forms of environmental
      complexity, and how both types of functional demands interact with phylogenetic
      and developmental constraints.

PMID- 17188554
TI  - Self-projection and the brain.
AB  - When thinking about the future or the upcoming actions of another person, we
      mentally project ourselves into that alternative situation. Accumulating data
      suggest that envisioning the future (prospection), remembering the past,
      conceiving the viewpoint of others (theory of mind) and possibly some forms of
      navigation reflect the workings of the same core brain network. These abilities
      emerge at a similar age and share a common functional anatomy that includes
      frontal and medial temporal systems that are traditionally associated with
      planning, episodic memory and default (passive) cognitive states. We speculate
      that these abilities, most often studied as distinct, rely on a common set of
      processes by which past experiences are used adaptively to imagine perspectives
      and events beyond those that emerge from the immediate environment.

PMID- 17188555
TI  - Object recognition and segmentation by a fragment-based hierarchy.
AB  - How do we learn to recognize visual categories, such as dogs and cats? Somehow,
      the brain uses limited variable examples to extract the essential characteristics
      of new visual categories. Here, I describe an approach to category learning and
      recognition that is based on recent computational advances. In this approach,
      objects are represented by a hierarchy of fragments that are extracted during
      learning from observed examples. The fragments are class-specific features and
      are selected to deliver a high amount of information for categorization. The same
      fragments hierarchy is then used for general categorization, individual object
      recognition and object-parts identification. Recognition is also combined with
      object segmentation, using stored fragments, to provide a top-down process that
      delineates object boundaries in complex cluttered scenes. The approach is
      computationally effective and provides a possible framework for categorization,
      recognition and segmentation in human vision.

PMID- 17188556
TI  - Frames and brains: elicitation and control of response tendencies.
AB  - Using magnetic resonance imaging, De Martino and colleagues investigated the
      neural signature that is associated with decisions between small sure amounts of
      money and large riskier amounts when the framing of the outcomes is varied. We
      interpret their results within a dual-system framework, in which different frames
      evoke distinct emotional responses that different individuals can suppress to
      various degrees. The study advances the integration of brain imaging results into
      cognitive theory.

PMID- 17188557
TI  - Chemical biology of steroid and nuclear hormone receptors.
AB  - The nuclear hormone receptors are ligand-gated transcription factors that
      modulate gene expression by directly acting upon genomic DNA, and have been of
      profound interest across all biological disciplines. Recent advancements in this
      area have included the expansion of transgene activation through ligand-receptor
      engineering, drug development from structural design and the exploitation of
      innate ligand-specific associations towards developing novel conditional protein
      based recombinant and diagnostic tools. These advancements come on the heels of
      exciting new modes of hormone action that challenge and expand upon the classic
      paradigms of hormone receptor function.

PMID- 17188558
TI  - Sudan I induces genotoxic effects and oxidative DNA damage in HepG2 cells.
AB  - Sudan I, a synthetic lipid soluble azo pigment, is widely used in various
      industrial fields. However, Sudan I has not been approved at any level of food
      production, since there are many inconclusive reports relating to its
      genotoxicity and carcinogenicity in humans. The aim of this study was to assess
      the genotoxic effects of Sudan I and to identify and clarify the reaction
      mechanisms by use of human hepatoma HepG2 cells. To study the genotoxic effects
      of Sudan I, the comet assay and micronucleus test (MNT) were used. In the comet
      assay and MNT, we found increase of DNA migration and of the micronuclei
      frequencies at all tested concentrations (25-100 microM) of Sudan I in a dose
      dependent manner. The data suggest that Sudan I caused DNA strand breaks and
      chromosome breaks. To elucidate the underlying mechanism of this difference, we
      monitored the level of reactive oxygen species (ROS) production with the 2,7
      dichlorofluorescein diacetate assay. The level of the oxidative DNA damage and
      lipid peroxidation was evaluated using immunoperoxidase staining for 8
      hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid
      reactive substances (TBARS). Significantly increased levels of ROS, 8-OHdG and
      TBARS were observed in HepG2 cells at higher concentrations, the doses being 100,
      50-100 and 50-100 microM, respectively. We conclude that Sudan I causes genotoxic
      effects, probably via ROS-induced oxidative DNA damage at the higher doses.

PMID- 17188559
TI  - Processes of molecular association and excimeric emission in protonated N,N
      dimethylformamide.
AB  - Formation of associates of N,N-dimethylformamide (DMF) molecules was studied to
      clarify their role in photoluminescent activity of protonated DMF solutions. The
      association of DMF molecules was observed in dilute aqueous solutions at
      concentrations of DMF above approximately 4x10(-2) M. The association is enhanced
      when the CO bond of the DMF molecule is activated by protonation with
      hydrochloric acid, which leads to appearance of an excimeric emission at
      approximately 530 nm. The excitation spectrum of the excimeric emission showed
      the excitation maximum in the region of the absorption of DMF associates, which
      is a first evidence of a more complex mechanism of excimer formation originating
      from excitation of associated rather than monomeric molecules in the ground
      state. A simple approach was provided to evaluate a number of molecules in the
      excimer structure. An original theory has been developed, and it was calculated
      that the DMF excimer has a dimeric nature. A model of the excimer formation was
      proposed, which suggests that a hydrogen-bonded associate is an intermediate form
      leading to the excimeric structure upon excitation. It was observed that DMF
      possesses also a monomeric emission with the emission maximum at approximately
      385 nm, which was attributed to the intramolecular charge-transfer process. It
      has been found that the change in structure of the DMF associates via the liquid
      solid phase transition affects both excitation and emission bands of excimers, so
      that the excimeric emission shifts to the blue region and intermixes with the
      emission of DMF monomers.

PMID- 17188560
TI  - Electronic structure and solvatochromism of merocyanines NMR spectroscopic point
      of view.
AB  - (1)H and (13)C NMR spectra of two series of malononitrile-based merocyanines,
      which possess positive and negative solvatochromism have been in detail
      investigated in low polar chloroform and polar dimethyl sulfoxide (DMSO). Careful
      attribution of signals in spectra has been made with the help of two-dimensional
      NMR experiments (COSY, NOESY, HMBC, and HMQC). Hence, the dependence of
      merocyanines electronic structure on their chemical structure and solvent nature
      has been studied by this powerful method. It has been shown that there exists a
      good correlation between the calculated charges on carbon atoms of a polymethine
      chain and their chemical shifts in (13)C NMR spectra. The influence of solvent
      polarity on bond orders for dyes with positive and negative solvatochromism is
      also observed. The comparison of (13)C NMR spectra of merocyanines and
      corresponding parent ionic dyes allows to determine their sign of solvatochromism
      irrespectively of electronic spectra, and also to find the key atoms of
      chromophore whose signals in (13)C NMR spectra are most informative.

PMID- 17188561
TI  - Structure elucidation of cresylviolet perchlorate in polyvinylbutyral by the
      joint application of IR, FTIR, Raman, UV and visible spectroscopy.
AB  - Infrared, Fourier transform infrared, Raman, UV absorption and emission spectra
      of cresylviolet perchlorate (CV) in polyvinylbutyral (PVB) were recorded in the
      region 1250-4000 cm(-1) at room temperature and assignments have been made for
      the observed absorption emission and Raman scattered lines.

PMID- 17188562
TI  - FT-IR and NMR investigation of 2-(1-cyclohexenyl)ethylamine: a combined
      experimental and theoretical study.
AB  - FT-IR and (1)H, (13)C, DEPT, HETCOR, COSY, and NOESY NMR spectra of 2-(1
      cyclohexenyl)ethylamine (CyHEA) have been reported for the first time. The
      vibrational frequencies and (1)H, (13)C NMR chemical shifts of CyHEA (C(8)H(15)N)
      have been calculated by means of the Hartree-Fock (HF), Becke-Lee-Yang-Parr
      (BLYP) and Becke-3-Lee-Yang-Parr (B3LYP) density functional methods with 6-31
      G(d) and 6-31 G(d,p) basis sets, respectively. The comparison between the
      experimental and the theoretical results indicates that density functional B3LYP
      method is superior to the scaled HF and BLYP approach for vibrational frequencies
      and predicting NMR properties.

PMID- 17188563
TI  - Synthesis and characterization of N,N'-bis[2-hydroxyethyl]-1,4,6,8
      naphthalenediimide with para substituted of phenols based on charge-transfer
      complexes.
AB  - The interaction of charge-transfer (CT) complexes resulted from the reaction of
      N,N'-bis[2-hydroxyethyl]-1,4,6,8-naphthalenediimide (BHENDI) with some various
      acceptors like as substituted phenols in para position; 4-aminophenol (4AP), 4
      methylphenol (4MP) and 4-nitrophenol (4NP) have been studied in methanol at room
      temperature. The reaction was studied using electronic (UV-vis), mid infrared,
      and (1)H NMR spectra and thermal measurements (TGA and DTG) as well as elemental
      analysis CHN. The chemical analysis data of the resulted CT-complexes, BHENDI
      acceptors, reveal that the formation of a 1:2 CT complexes in all cases. The
      interaction of N,N'-bis[2-hydroxyethyl]-1,4,6,8-naphthalenediimide and phenolic
      acceptors were investigated spectrophotometrically and found two detected CT
      bands have n-pi(*) transition. The donor site involved in CT interaction is the
      diimide two nitrogen atoms by forming hydrogen bonding. The kinetic thermodynamic
      parameters like DeltaE, DeltaH, DeltaS and DeltaG are calculated from the DTG
      diagrams using Coats-Redfern method. The electrical conductivity properties for
      the solid CT complexes were measured within the temperature of room 25 degrees C.

PMID- 17188564
TI  - The impact of patient-physician web messaging on healthcare service provision.
AB  - BACKGROUND: Information technology can support the delivery of healthcare.
      Patients are eager to make use of such tools as web messaging, yet its deployment
      has been limited to date. A fear still pervades that the cost associated with a
      possible increase to physician workloads may outweigh any suggested benefits.
      GOAL: This paper aims to review the body of research completed in the area of
      patient-physician web messaging. The findings of this review will then be
      assessed and synthesised, with the intention of creating an overview of both the
      benefits and costs of patient-physician online messaging. Areas of particular
      importance to future research may then be identified. RESULTS: Demand and support
      for online communication tools amongst patients is strong, and can increase
      quality of care due to increased patient-physician communication. Although there
      would seem to be great potential to increase process efficiency, there would not
      seem to be sufficient evidence as of yet to suggest that this is the case.
      CONCLUSION: Further quantitative research in particular is required to assess the
      impact of online communication, with special regard to the effect on overall
      patient demand and on healthcare process efficiency.

PMID- 17188565
TI  - Dynamics of response-conflict monitoring and individual differences in response
      control and behavioral control: an electrophysiological investigation using a
      stop-signal task.
AB  - OBJECTIVES: The aim of the present study was to investigate the functional
      significance of error (related) negativity Ne/ERN and individual differences in
      human action monitoring. A response-conflict model of Ne/ERN should be tested
      applying a stop-signal paradigm. After a few modifications of Ne/ERN response
      conflict theory (Yeung N, Botvinick MM, Cohen JD. The neural basis of error
      detection: conflict monitoring and the error-related negativity. Psychological
      Review 2004:111(4);931-959), strength and time course of response conflict could
      be modeled as a function of stop-signal delay. METHOD: In Experiment 1, 35
      participants performed a visual two-choice response-time task but tried to
      withhold the response if an auditory stop signal was presented. Probability of
      stopping errors was held at 50% using variable delays between visual and auditory
      stimuli. Experiment 2 (n=10) employed both auditory go and stop signals and
      confirmed that Ne/ERN effects are due to conflict induced by the auditory stop
      signal, and not the mere presence or absence of an additional stimulus. RESULTS:
      As predicted, amplitudes of both the stimulus-locked and response-locked Ne/ERN
      were largest for non-stopped responses, followed by successfully stopped and go
      responses. However, independently of response type Ne/ERN also increased with
      increasing stop-signal delay. Since longer delay invokes stronger response
      conflict, results specifically support the notion of Ne/ERN reflecting response
      conflict monitoring. Furthermore, individual differences related to measures of
      response control and behavioral control were observed. Both low response control
      estimated from stop-task performance and high psychometric impulsivity were
      accompanied by smaller Ne/ERN amplitude on stop trials, suggesting reduced
      response-conflict monitoring. CONCLUSIONS: The present study supported the
      response-conflict view of Ne/ERN. Furthermore, the observed relationship between
      impulsivity and Ne/ERN amplitude suggested that individuals with low behavioral
      control were characterized by lower activity in anterior cingulate cortex, the
      neural generator of Ne/ERN, in situations of strong response conflict.
      SIGNIFICANCE: The present study, for the first time, employed a stop-signal
      paradigm to verify predictions regarding the temporal dynamics of response
      conflict processing as derived from response-conflict theory of ERN.

PMID- 17188566
TI  - Signal-to-noise ratio of chemosensory event-related potentials.
AB  - OBJECTIVE: We investigated the influence of the number of stimuli on signal-to
      noise (S/N) ratio of CSERP. METHODS: CSERP from 20 normosmic subjects were
      obtained in response to stimulation with two olfactory (H(2)S and PEA) and a
      trigeminal (CO(2)) stimulant. For each of these odors, 160 stimuli were delivered
      into the right nostril (duration 200ms, mean ISI 30s) using a constant-flow, air
      dilution olfactometer. For each EEG recording site (Fz, Cz, Pz, C3, C4), peak-to
      peak amplitude N1P2 and noise amplitude levels were determined. Subsequently, S/N
      ratios were calculated. RESULTS: The S/N ratios for olfactory ERP generally
      improved for H(2)S and PEA. For responses to PEA, S/N ratios increased
      significantly up to 80 averages (S/N ratio=5.6). The number of stimuli for an
      optimal S/N ratio for trigeminal ERP was slightly lower, i.e. 60 averages (S/N
      ratio=7.9). CONCLUSIONS: S/N N1P2 ratios in olfactory and trigeminal ERP
      significantly improve with an increasing number of responses averaged under these
      experimental conditions. This is mainly due to a reduction of noise level.
      Applying more stimuli has little additional effect on S/N ratio due to a
      concomitant decrease in signal amplitude. SIGNIFICANCE: An optimal S/N ratio is
      essential when recording CSERP in neurodegenerative disorders, where responses
      may be of low amplitude, and for medico-legal purposes.

PMID- 17188567
TI  - Event-related variations in alpha band activity during an attentional task in
      preadolescents: Effects of morning nutrition.
AB  - OBJECTIVE: Event-related desynchronization and synchronization (ERD/ERS)
      methodology was used to study interactions between nutrition, brain function,
      cognition and behavior in children who ate or skipped breakfast after overnight
      fasting. METHODS: Healthy preadolescents performed a cued visual Go/No-Go RT task
      after overnight fasting (Phase 1) and again (Phase 2) after eating breakfast
      (n=30) or continuing to fast (n=30). ERS and ERD determinations (8-10, 10-12Hz;
      frontal, central, parietal, occipital sites) and measures of sleep (overnight
      actigraphy) and blood glucose (finger sticks) were obtained. RESULTS: Feeding
      increased blood glucose, but the groups were similar in sleep amount and response
      accuracy. Between-phase comparisons showed slower RT and increased alpha
      synchronization in fasting subjects, but little change in those who ate
      breakfast. Phase 2 group differences emphasized greater frontal early ERS and
      late frontal-central ERD in Fed subjects. CONCLUSIONS: In preadolescents a brief
      extension of overnight fasting resulted in significant changes in brain activity
      and behavior that were effectively countered by eating breakfast. Delaying
      breakfast until mid-morning appeared to have introduced fasting effects that
      attenuated responses in Fed subjects. SIGNIFICANCE: These findings show the
      sensitivity of brain function and behavior to subtle variations in nutritional
      status and argue for greater consideration of nutritional variables in
      neurobehavioral studies.

PMID- 17188568
TI  - A real electro-magnetic placebo (REMP) device for sham transcranial magnetic
      stimulation (TMS).
AB  - OBJECTIVE: There is growing interest in neuropsychiatry for repetitive
      transcranial magnetic stimulation (rTMS) as a neuromodulatory treatment. However,
      there are limitations in interpreting rTMS effects as a real consequence of
      physiological brain changes or as placebo-mediated unspecific effects, which may
      be particularly strong in psychiatric patients. This is due to the fact that
      existing sham rTMS procedures are less than optimal. A new placebo tool is
      introduced here, called real electro-magnetic placebo (REMP) device, which can
      simulate the scalp sensation induced by the real TMS, while leaving both the
      visual impact and acoustic sensation of real TMS unaltered. METHODS: Physical,
      neurophysiological and behavioural variables of monophasic and biphasic single
      pulse TMS and biphasic 1Hz and 20Hz rTMS procedures (at different intensities)
      were tested in subjects who were expert or naive of TMS. Results of the real TMS
      were compared with those induced by the REMP device and with two other currently
      used sham procedures, namely the commercially available Magstim sham coil and
      tilting the real coil by 90 degrees . RESULTS: The REMP device, besides producing
      scalp sensations similar to the real TMS, attenuated the TMS-induced electric
      field (as measured by a dipole probe) to a biologically inactive level.
      Behaviourally, neither expert nor naive TMS subjects identified the "coil at 90
      degrees " or the "Magstim sham coil" as a real TMS intervention, whilst naive
      subjects were significantly more likely to identify the REMP-attenuated TMS as
      real. CONCLUSIONS: The "goodness of sham" of the REMP device is demonstrated by
      physical, neurophysiological, and behavioural results. SIGNIFICANCE: Such placebo
      TMS is superior to the available sham procedures when applied on subjects naive
      to TMS, as in case of patients undergoing a clinical rTMS trial.

PMID- 17188569
TI  - Clinical trials update from the American Heart Association 2006: OAT, SALT 1 and
      2, MAGIC, ABCD, PABA-CHF, IMPROVE-CHF, and percutaneous mitral annuloplasty.
AB  - This article provides information and a commentary on trials presented at the
      American Heart Association meeting held in November 2006, relevant to the
      pathophysiology, prevention and treatment of heart failure. All reports should be
      considered as preliminary data, as analyses may change in the final publication.
      The OAT study failed to show a benefit of PCI over optimal medical therapy in
      patients with persistent total occlusion of the infarct related artery following
      a myocardial infarction. In SALT 1 and 2, tolvaptan was found to correct
      hyponatraemia of various aetiologies; however, whether this has an impact on
      heart failure prognosis requires further evaluation. A placebo controlled study
      of myocardial implantation of skeletal myoblasts in patients with moderate to
      severe LVSD (MAGIC) showed equivocal/uncertain effects, long term follow-up data
      are awaited. The ABCD study which compared the ability of an invasive and a non
      invasive test to identify patients at risk of arrhythmic events prior to ICD
      implantation, suggested that the two strategies were comparable, although the
      practical value of either test remains uncertain and the study had many major
      flaws. The PABA-CHF study hinted that pulmonary vein antrum isolation might be
      more effective than AV node ablation with bi-ventricular pacing for the treatment
      of patients with heart failure in atrial fibrillation. In IMPROVE-CHF, an NT-pro
      BNP guided treatment strategy was found to reduce the cost of managing patients
      with acute breathlessness.

PMID- 17188570
TI  - Angiopoietin-1 for myocardial angiogenesis: a comparison between delivery
      strategies.
AB  - We compare the effectiveness of direct adenoviral angiopoietin-1 (Ad-Ang-1)
      injection with transplantation of skeletal myoblasts (SkMs) over-expressing
      angiopoietin-1 (Ang-1) for angiogenic response and improvement of heart function
      in an experimental porcine model of myocardial infarction (MI). METHODS: Ad-Ang-1
      was used for intramyocardial injection or transduction of SkMs. Three weeks after
      coronary artery ligation in 32 female pigs, animals were grouped to receive
      multiple intramyocardial injections of DMEM without cells (group-1; n=7), or
      containing 3 x 10(8)Lac-z labelled SkMs transduced with Ad-Null vector carrying
      no gene (group-2; n=7), or 1 x 10(10) PFU Ad-Ang-1 (group-3; n=9), or 3 x
      10(8)Lac-z labelled SkMs transduced with Ad-Ang-1 (group-4; n=9). The animals
      were immunosuppressed for 6-weeks. After euthanasia, their heart tissue was
      processed for histological studies. RESULTS: Extensive survival of Lac-z positive
      SkMs was observed in and around the infarct 6 and 12-weeks after transplantation.
      Fluorescent immunostaining for vWF-VIII at 6-weeks revealed increased blood
      vessel density (x100) in group-4 (p<0.05) as compared with other groups. Regional
      blood flow (ml/g/min) in the peri-infarct area was improved in group-4 (2.7;
      p<0.05) as compared with group-1 (1.2+/-0.1), group-2 (1.1+/-0.4) and group-3
      (1.7+/-0.1) at 6-weeks. Similarly, ejection fraction was significantly higher in
      group-4 (49.2+/-5.9%, p=0.03) as compared with group-1 (36.8+/-3%) at 6 weeks.
      CONCLUSION: SkMs mediated Ang-1 delivery is associated with improved angiogenic
      response, regional myocardial perfusion and heart function as compared with
      direct Ad-Ang-1 administration.

PMID- 17188571
TI  - Use of aortic homograft conduit in bidirectional Glenn shunt.
AB  - We present our experience with a patient in whom a homograft conduit was used to
      connect the superior vena cava (SVC) to the right pulmonary artery (RPA) in a
      functionally univentricular heart where corrective repair was impossible.

PMID- 17188572
TI  - The road to recovery: translating PD-1 biology into clinical benefit.
AB  - Negative immune regulation can result in the poor control of virus replication in
      chronic infections but is probably important to prevent tissue damage from
      chronic immune activation. Three recent studies have shown that programmed cell
      death (PD)-1 expression on T cells correlates with viral load in HIV infection,
      and that interrupting PD-1 signaling using an antagonistic antibody rejuvenates T
      cell effector functions in vitro. These findings have important implications for
      potential therapies for chronic infection and, perhaps, for improved tumor
      immunity. Here, we discuss impending issues in the translation to clinical
      studies in light of recent adverse events with costimulatory antibody therapy.

PMID- 17188573
TI  - The Okinawa Infectious Diseases Initiative.
AB  - At the Kyushu-Okinawa Group of Eight summit in 2000, Japan announced the Okinawa
      Infectious Diseases Initiative (IDI) and pledged to spend US$3 billion over a
      five year period to combat infectious and parasitic diseases in developing
      countries. The IDI has exceeded expectations, spending more than US$4 billion
      over four years. The IDI is a unique initiative with its own philosophical basis
      and specifically tailored interventions and measures that helped to initiate
      worldwide political and financial commitments in the fight against infectious
      diseases. Notably, it promoted partnerships among stakeholders and emphasized
      comprehensive and inter-sectoral approaches (i.e. coordination and collaboration
      between health and other sectors). It helped to create a new vision of what is
      possible in the global effort against communicable diseases and has been
      instrumental in shaping the changing environments of development assistance,
      poverty reduction and other trends to reduce the impact of infectious and
      parasitic diseases.

PMID- 17188574
TI  - Population dynamics of Plasmodium sporogony.
AB  - Malaria transmission relies on the sporogonic development of Plasmodium parasites
      within insect vectors. Sporogony is a complex process that involves several
      morphologically distinct life-stages and can be described in terms of population
      dynamics: changes in the abundance and distribution of successive life-stages
      throughout development. Recent publications on the population dynamics of
      sporogony are reviewed, with special attention to the differences and
      similarities among the parasite-vector systems examined thus far. Understanding
      the population dynamics of malaria parasites within their natural vectors will
      lead to a better understanding of how malaria parasites survive and are
      maintained within mosquitoes.

PMID- 17188575
TI  - CSF enrichment of highly differentiated CD8+ T cells in early multiple sclerosis.
AB  - CD8+ T cells may play an important role in multiple sclerosis (MS). Whether these
      cells would be involved in early stages of MS is unclear. We enrolled 52 patients
      with suspected MS, determined the recruitment of their highly differentiated
      (CCR7-/CD45RA+ or -) T cells (T(HD)) in the CSF as compared to peripheral blood
      and followed them for 12+/-7.3 months. A ROC curve showed that a CD8+/CD4+ T(HD)
      cells ratio of 0.94 helped to distinguish relapsing-remitting (RR-MS) and
      possible MS (Po-MS) from primary-progressive MS (PP-MS) and other neurological
      diseases patients (OND) patients (p=0.039), risk ratio of 2.29 (95% CI: 1.13
      4.66; p=0.006). The CSF enrichment in CD8+ T(HD) cells was greater than in CD4+
      T(HD) cells in RR/Po-MS patients (p=0.024) and than in CD8+ T(HD) cells in PP
      MS/OND patients (p=0.006). These data suggest that CD8+ T(HD) cells play a role
      in the early stages of RR-MS.

PMID- 17188576
TI  - Normal levels of constitutive and death receptor-mediated apoptosis of peripheral
      blood neutrophils from patients with chronic idiopathic neutropenia.
AB  - To investigate the role of neutrophil apoptosis in the pathogenesis of chronic
      neutropenia, we examined constitutive and death receptor-mediated apoptosis ex
      vivo of peripheral blood neutrophils obtained from six chronic idiopathic
      neutropenia (CIN) patients and six healthy adult blood donors. Apoptosis was
      quantified based on phosphatidylserine externalization and caspase-3 activation
      in freshly isolated neutrophils or after overnight cultivation of neutrophils in
      the absence or presence of pro- or anti-apoptotic factors, including the pan
      caspase inhibitor, zVAD-fmk. Neutrophils from CIN patients receiving treatment
      with granulocyte colony-stimulating factor appeared to be more prone to
      constitutive apoptosis than cells from untreated patients; however, further
      investigations in larger cohorts of patients are needed to validate these pilot
      studies. Overall, the level of neutrophil apoptosis was similar in patient and
      control groups, thus supporting the notion that the underlying defect in these
      neutropenia patients lies elsewhere, such as in the bone marrow microenvironment.

PMID- 17188577
TI  - Retrieving autobiographical memories of painful events activates the anterior
      cingulate cortex and inferior frontal gyrus.
AB  - Patients will often reflect on the meaning of a painful episode, as, for example,
      when completing questionnaire measures of subjective pain experience or in
      clinical interviews. Neuroimaging studies of the human cortical and subcortical
      physical pain response have identified a neural network consistently referred to
      as the "pain matrix." We used functional magnetic resonance imaging to
      investigate whether the pain matrix could be activated through the retrieval of
      memories relating to previously painful events, in the absence of any direct
      peripheral noxious input. Fourteen pain-free participants were explicitly
      instructed to recall autobiographical memories of painful episodes in response to
      pain-related words and non-painful episodes in response to equally salient but
      non-pain words. Memories triggered by pain-related words produced significantly
      greater activation of left caudal anterior cingulate cortex (BA32'), and left
      inferior frontal gyrus (BA44, extending to BA47/45) more than memories triggered
      by equally salient but non-pain words. We suggest that these activations
      demonstrate a semantic retrieval process for pain-related memories, which may
      provide a means of cognitively reappraising the memory of the painful episode,
      thus allowing the person to elaborate on the circumstances surrounding the event,
      without physically re-experiencing it. PERSPECTIVE: The present study reveals a
      putative neural mechanism for the retrieval of autobiographical memories of
      previously painful events, which may provide a means of cognitively reappraising
      a painful episode, without physically re-experiencing it. This finding has
      implications for understanding disease mechanisms of chronic pain and their
      impact on subsequent treatment.

PMID- 17188578
TI  - Quantitative oral dosing of water soluble and lipophilic contaminants in the
      Japanese medaka (Oryzias latipes).
AB  - Quantitative oral dosing in fish can be challenging, particularly with water
      soluble contaminants, which can leach into the aquarium water prior to ingestion.
      We applied a method of bioencapsulation using newly hatched brine shrimp (Artemia
      franciscana) nauplii to study the toxicokinetics of five chlorinated and
      brominated halogenated acetic acids (HAAs), which are drinking water disinfection
      by-products. These results are compared to those obtained in a previous study
      using a polybrominated diphenyl ether (PBDE-47), a highly lipophilic chemical.
      The HAAs and PBDE-47 were bioencapsulated using freshly hatched A. franciscana
      nauplii after incubation in concentrated solutions of the study chemicals for 18
      h. Aliquots of the brine shrimp were quantitatively removed for chemical analysis
      and fed to individual fish that were able to consume 400-500 nauplii in less than
      5 min. At select times after feeding, fish were euthanized and the HAA or PBDE-47
      content determined. The absorption of HAAs was quantitatively similar to previous
      studies in rodents: rapid absorption with peak body levels occurring within 1-2
      h, then rapidly declining with elimination half-life of 0.3-3 h depending on HAA.
      PBDE-47 was more slowly absorbed with peak levels occurring by 18 h and very
      slowly eliminated with an elimination half-life of 281 h.

PMID- 17188579
TI  - Sensitivity of expression of perivitelline membrane glycoprotein ZP1 mRNA in the
      liver of Japanese quail (Coturnix japonica) to estrogenic compounds.
AB  - Avian perivitelline membrane protein, ZP1, is synthesized and secreted by the
      liver with the stimulation of estrogens. In the present study, we measured the
      expression of ZP1 gene in the liver of immature male quail treated with various
      estrogenic compounds and in the liver of male quail embryos that were developed
      in the fertilized eggs laid by mother quail injected with various estrogenic
      compounds during vitellogenesis. Total RNA extracted from the liver was reverse
      transcribed and cDNA was subjected to real-time PCR. Both diethylstilbestrol and
      ethinyl estradiol caused significant effect on the increase in mRNA in immature
      male quail. In contrast, diethylstilbestrol administered via the route of
      maternal injection was not effective for induction of embryonic mRNA, although
      the effect of ethinyl estradiol administered via the same route was prominent.
      These results showed that direct administration of estrogenic compounds,
      diethylstilbestrol and ethinyl estradiol, stimulates the induction of ZP1 gene,
      but the rate of accumulation of these compounds in the yolk is different during
      vitellogenesis. The present studies suggest that although ZP1 gene is a sensitive
      biomarker to evaluate the effects of endocrine disruptors, the route of
      administration is an important factor to compare the effectiveness.

PMID- 17188580
TI  - Relaxant effects of danshen aqueous extract and its constituent danshensu on rat
      coronary artery are mediated by inhibition of calcium channels.
AB  - In this study, we have investigated the actions of danshensu, an active, water
      extractable component of the medicinal herb danshen (Salvia miltiorrhiza), on rat
      isolated coronary artery rings precontracted with 1 microM 5-hydroxytryptamine (5
      HT) and its action compared to the water-extractable fraction of the herb.
      Extraction of the water-soluble fraction from danshen (S. miltiorrhiza) provided
      yield of 17.5% (35 g/200 g). The amount of danshensu determined in the crude
      danshen herb and in its aqueous fraction was 0.45 mg/g (0.045%) and 3.28 mg/g
      (0.33%). The danshen aqueous extract was 13 times less potent than danshensu in
      relaxing 5-HT-precontracted coronary artery rings; IC50 values were 930.3+/-133.5
      microg/ml and 71.5+/-11.0 microg/ml. Removal of the endothelium did not
      significantly affect their vasodilator potencies; IC50 values were 842.1+/-123.8
      microg/ml and 84.8+/-8.8 microg/ml. On the other hand, a potassium channel
      inhibitor tetraethylammonium (TEA, 10 mM) shifted their concentration-response
      curves by 1.7 and 2.2 folds. The possible involvement of Ca2+ channels was
      investigated in artery rings incubated with Ca2+-free buffer and primed with 1
      microM 5-HT or 60 mM KCl for 5 min prior to addition of CaCl2 to elicit
      contraction. In 5-HT-primed preparations, the CaCl2-induced vasoconstriction was
      abolished by 2 mg/ml danshen aqueous extract and 200 microg/ml danshensu,
      whereas, in KCl-primed preparations, 10 mg/ml danshen aqueous extract and 600
      microg/ml danshensu were required to abrogate the vasoconstriction. These
      findings suggest the vasorelaxant actions of danshen aqueous extract and
      danshensu were produced by inhibition of Ca2+ influx in the vascular smooth
      muscle cells. The opening of K+ channels had a minor contribution to the
      response, but endothelium-dependent mechanisms were not involved.

PMID- 17188581
TI  - The Best Bypass Surgery Trial: rationale and design of a randomized clinical
      trial with blinded outcome assessment of conventional versus off-pump coronary
      artery bypass grafting.
AB  - BACKGROUND: Recent trials suggest that off-pump coronary artery bypass grafting
      (OPCAB) reduces the risk of mortality and morbidity compared with conventional
      coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients
      with a moderate- to high-risk of complications after CCAB may have additional
      benefit from OPCAB. METHODS: The Best Bypass Surgery Trial is a randomized,
      single center trial comparing the effects of OPCAB versus CCAB. The inclusion
      criteria are 3 vessel coronary heart disease affecting one of the marginal
      arteries, age>54 years, and EuroSCORE>or=5. The primary composite outcome measure
      consists of all-cause mortality, myocardial infarction, stroke, cardiac arrest,
      cardiogenic shock, and cardiac revascularization procedure. Follow up involves
      collection of data of mortality and morbidity via linkage to public registers,
      quality of life assessment at 3 and 12 months postoperatively and angiographic
      control at 12 months. The sample size of 330 patients was based on an estimated
      75% one-year event free rate of the primary outcome measure in the OPCAB arm and
      60% in the control arm with alpha=.05 and beta=.20. Accordingly, the trial will
      be able to detect an absolute risk reduction of 15% or a relative risk reduction
      of 37.5%. The median follow-up time is scheduled to 3 years. RESULTS: Enrollment
      started in April 2002 and ended March 2006. CONCLUSION: The results may have
      implications on the treatment modality of moderate- to high-risk patients
      scheduled for coronary artery bypass grafting.

PMID- 17188583
TI  - Novel DNA lesions generated by the interaction between therapeutic thiopurines
      and UVA light.
AB  - The therapeutic effect of the thiopurines, 6-thioguanine (6-TG), 6
      mercaptopurine, and its prodrug azathioprine, depends on the incorporation of 6
      TG into cellular DNA. Unlike normal DNA bases, 6-TG absorbs UVA radiation, and
      UVA-mediated photochemical damage of DNA 6-TG has potentially harmful side
      effects. When free 6-TG is UVA irradiated in solution in the presence of
      molecular oxygen, reactive oxygen species are generated and 6-TG is oxidized to
      guanine-6-sulfonate (G(SO3)) and guanine-6-thioguanine in reactions involving
      singlet oxygen. This conversion is prevented by antioxidants, including the
      dietary vitamin ascorbate. DNA G(SO3) is also the major photoproduct of 6-TG in
      DNA and it can be selectively introduced into DNA or oligonucleotides in vitro by
      mild chemical oxidation. Thermal stability measurements indicate that G(SO3) does
      not form stable base pairs with any of the normal DNA bases in duplex
      oligonucleotides and is a powerful block for elongation by Klenow DNA polymerase
      in primer extension experiments. In cultured human cells, DNA damage produced by
      6-TG and UVA treatment is associated with replication inhibition and provokes a
      p53-dependent DNA damage response.

PMID- 17188582
TI  - Genetic variation in the mitochondrial enzyme carbamyl-phosphate synthetase I
      predisposes children to increased pulmonary artery pressure following surgical
      repair of congenital heart defects: a validated genetic association study.
AB  - Increased pulmonary artery pressure (PAP) can complicate the postoperative care
      of children undergoing surgical repair of congenital heart defects. Endogenous NO
      regulates PAP and is derived from arginine supplied by the urea cycle. The rate
      limiting step in the urea cycle is catalyzed by a mitochondrial enzyme, carbamoyl
      phosphate synthetase I (CPSI). A well-characterized polymorphism in the gene
      encoding CPSI (T1405N) has previously been implicated in neonatal pulmonary
      hypertension. A consecutive modeling cohort of children (N=131) with congenital
      heart defects requiring surgery was prospectively evaluated to determine key
      factors associated with increased postoperative PAP, defined as a mean PAP>20
      mmHg for at least 1h during the 48h following surgery measured by an indwelling
      pulmonary artery catheter. Multiple dimensionality reduction (MDR) was used to
      both internally validate observations and develop optimal two-variable through
      five-variable models that were tested prospectively in a validation cohort
      (N=41). Unconditional logistic regression analysis of the modeling cohort
      revealed that age (OR=0.92, p=0.01), CPSI T1405N genotype (AC vs. AA: OR=4.08,
      p=0.04, CC vs. AA: OR=5.96, p=0.01), and Down syndrome (OR=5.25, p=0.04) were
      independent predictors of this complex phenotype. MDR predicted that the best two
      variable model consisted of age and CPSI T1405N genotype (p<0.001). This two
      variable model correctly predicted 73% of the outcomes from the validation
      cohort. A five-variable model that added race, gender and Down's syndrome was not
      significantly better than the two-variable model. In conclusion, the CPSI T1405N
      genotype appears to be an important new factor in predicting susceptibility to
      increased PAP following surgical repair of congenital cardiac defects in
      children.

PMID- 17188584
TI  - A GC-based metabonomics investigation of type 2 diabetes by organic acids
      metabolic profile.
AB  - "Metabonomics" method requires the development of rapid, advanced analytical
      tools and GC will play an important role for its special advantage. In this study
      we show the application of GC-based metabonomics to investigate the control and
      type 2 diabetes (DM2) patients by urinary organic acids metabolic profile. After
      peak matching, multivariate statistical analysis methods: principal components
      analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were
      used. The results showed that there was a relationship between organic acids
      metabolic profiles and DM2, and PLS-DA can distinguish the DM2 patients from the
      control. Five organic acids as potential biomarkers were identified.

PMID- 17188585
TI  - Sample clean-up with sol-gel enzyme and immunoaffinity columns for the
      determination of bisphenol A in human urine.
AB  - The paper describes the development of a simple and highly selective analytical
      method for the determination of free and total bisphenol A in urine samples. Free
      bisphenol A levels can be determined after sample clean-up using sol-gel
      immunoaffinity columns containing anti-bisphenol A antibodies. In determining
      total bisphenol A levels, the sample pre-treatment procedure consists of sample
      preparation using an on-line combination of two sol-gel columns, an enzyme column
      containing glucuronidase and arylsulfatase, and an immunoaffinity column.
      Bisphenol A can then be quantified by high-performance liquid chromatography and
      fluorescence detection. The mean recovery was found to be 78% with a standard
      deviation of 3.4%, the LOD (S/N=3) was 0.2 ng/ml. The method was applied to
      determine free and total urinary BPA levels of healthy adults and dialysis
      patients.

PMID- 17188586
TI  - Rat plasma proteomics: effects of abundant protein depletion on proteomic
      analysis.
AB  - The proteomic analysis of plasma and serum samples represents a formidable
      challenge due to the presence of a few highly abundant proteins such as albumin
      and immunoglobulins. Detection of low abundance protein biomarkers requires
      therefore either the specific depletion of high abundance proteins with
      immunoaffinity columns and/or optimized protein fractionation methods based on
      charge, size or hydrophobicity. Here we describe the depletion of seven abundant
      rat plasma proteins with an immunoaffinity column with coupled antibodies
      directed against albumin, IgG, transferrin, IgM, haptoglobin, fibrinogen and
      alpha1-anti-trypsin. The IgY-R7-LC2 (Beckman Coulter) column showed high
      specificity for the targeted proteins and was able to efficiently remove most of
      the albumin, IgG and transferrin from rat plasma samples as judged by Western
      blot analysis. Depleted rat plasma protein samples were analyzed by SELDI-TOF MS,
      2D SDS-PAGE and 2D-LC and compared to non-depleted plasma samples as well as to
      the abundant protein fraction that was eluted from the immunoaffinity column.
      Analysis of the depleted plasma protein fraction revealed improved signal to
      noise ratios, regardless of which proteomic method was applied. However, only a
      small number of new proteins were observed in the depleted protein fraction.
      Immunoaffinity depletion of abundant plasma proteins results in the significant
      dilution of the original sample which complicates subsequent analysis. Most
      proteomic approaches require specialized sample preparation procedures during
      which significant losses of less abundant proteins and potential biomarkers can
      occur. Even though abundant protein depletion reduces the dynamic range of the
      plasma proteome by about 2-3 orders of magnitude, the difference between medium
      abundant and low abundant plasma proteins is still in the range of 7-8 orders of
      magnitude and beyond the dynamic range of current proteomic technologies. Thus,
      exploring the plasma proteome in greater detail remains a daunting task.

PMID- 17188587
TI  - Solution structure of the second SH3 domain of human CMS and a newly identified
      binding site at the C-terminus of c-Cbl.
AB  - CMS, cas ligand with multiple Src homology 3 (SH3) domains, belongs to a family
      of ubiquitously expressed adaptor proteins. Among the CMS binding proteins, c-Cbl
      has been mostly extensively studied. It was reported that the motif PKPFPR
      (residues 824-829) of c-Cbl can bind to the N-terminus SH3 domains of CMS. Here
      we report the solution structure of the second SH3 domain of CMS (CMS_SH3_B),
      furthermore, we have identified that a peptide from residues 701 to 714 of c-Cbl
      (Cbl-p), i.e. MTPSSRPLRPLDTS, can specially bind to CMS_SH3_B using NMR chemical
      shift perturbation, suggesting that the peptide is a new potential CMS binding
      site. Among the peptide, TPSSRPLR is the core binding motif and Arg709 plays a
      key role in the interaction. Cbl-p binding interface on CMS_SH3_B along a
      hydrophobic channel is composed of RT loop, n-Src loop and beta4 strand and
      divided into three pockets. This work indicates the solution structure of
      CMS_SH3_B bears the canonical beta-beta-beta-beta-alpha-beta fold and a new
      binding site in c-Cbl involved in its interaction with CMS, which probably
      contributes to the clustering of CMS. All the information provided here should be
      beneficial for the future functional study of CMS.

PMID- 17188588
TI  - PTHrP, calcitonin and calcitriol in a case of severe, protracted and refractory
      hypercalcemia due to a pancreatic neuroendocrine tumor.
AB  - A patient with a primary neuroendocrine tumor of the pancreas, presented with
      severe hypercalcemia. This hypercalcemia of malignancy (HCM) failed to respond to
      intensive bisphosphonate treatment and needed continuous enhanced diuresis. Only
      after successful antitumor therapy did the hypercalcemia subside. Hypercalcemia
      was associated with increased concentrations of plasma PTHrP, calcitonin and 1,25
      (OH)(2)D(3). Bone mineral density was markedly increased. We demonstrated the
      presence of both PTHrP and calcitonin in the tumor at the mRNA and protein level,
      using RT-PCR, immunohistochemistry and Western blotting. The high levels of
      plasma PTHrP and the demonstrated predominant renal mechanism in this case of HCM
      are suspected to be the cause for its refractoriness to bone resorption
      inhibitors. Our findings furthermore suggest that the tumoral production of
      calcitonin and PTHrP might have contributed to the increased bone mineral storage
      of calcium and thus probably attenuated the development of frank hypercalcemia.

PMID- 17188589
TI  - Epimedium-derived phytoestrogen exert beneficial effect on preventing steroid
      associated osteonecrosis in rabbits with inhibition of both thrombosis and lipid
      deposition.
AB  - OBJECTIVES: This study tested the effect of Epimedium-derived phytoestrogen (PE)
      on preventing steroid-associated osteonecrosis (ON) in rabbit model. METHODS:
      Thirty 28-week-old male New-Zealand white rabbits were divided into control group
      (CON; n=14) and PE group (PE; n=16; 5 mg/kg body weight/day) after receiving an
      established inductive protocol for inducing steroid-associated ON. Before and
      after inductive protocol, Dynamic-MRI was employed on bilateral femora for local
      intra-osseous perfusion, blood samples were examined for coagulation,
      fibrinolysis and lipid-transportation, and marrow samples were quantified for
      adipogenesis-gene mRNA expression. Six weeks later, bilateral femora were
      dissected for Micro-CT-based micro-angiography, and then ON lesion, intravascular
      thrombosis and extravascular fat-cell-size were examined histopathologically.
      RESULTS: The incidence of ON in the PE group (31%) was significantly lower than
      that in the CON group (93%). Compared to the CON group, local intra-osseous
      perfusion was maintained in the PE group. Blocked trunk vessels were seldom found
      in micro-angiography of the PE-treated rabbits. Thrombosis incidence and fat-cell
      size were both significantly lower in the PE group than those in the CON group.
      During the early period after induction, indicator of coagulation, fibrinolysis,
      lipid-transportation and adipogenesis-gene expression were found with
      significantly changing pattern in the PE group compared to the CON group.
      CONCLUSION: PE was able to exert beneficial effect on preventing steroid
      associated ON in rabbits with inhibition of both thrombosis and lipid deposition.

PMID- 17188590
TI  - Automated osteoporosis risk assessment by dentists: a new pathway to diagnosis.
AB  - General dental practitioners use a vast amount of panoramic radiography in their
      routine clinical work, but valuable information about patients' osteoporotic
      status is not collected. There are many reasons for this, but one of the prime
      reasons must be the disruption involved in clinical routine with lengthy manual
      radiographic assessment. We have developed computer software, based on active
      shape modeling that will automatically detect the mandibular cortex on panoramic
      radiographs, and then measure its width. Automatic or semi-automatic measurement
      of the cortical width will indicate the osteoporotic risk of the patient. The aim
      of our work was to assess the computer search technique's ability to measure the
      mandibular cortical width and to assess its potential for detection of
      osteoporosis of the hip, spine and femoral neck. Mandibular cortical width was
      measured using the manually initialized (semi-automatic) method and, when
      assessed for diagnosing osteoporosis at one of the three measurement sites, gave
      an area under the ROC curve (A(z))=0.816 (95% CI=0.784 to 0.845) and for the
      automatically initialized searches, A(z)=0.759 (95% CI=0.724 to 0.791). The
      difference between areas=0.057 (95% Confidence interval=0.025 to 0.089),
      p<0.0001. For diagnosing osteoporosis at the femoral neck, mandibular cortical
      width derived from the manually initialized fit gave an area under the ROC curve
      (A(z))=0.835 (95% CI=0.805 to 0.863) and for the automatically initialized
      searches A(z)=0.805 (95% CI=0.773 to 0.835). The difference in A(z) values
      between active shape modeling search methods=0.030 (95% CI=-0.010 to 0.070), and
      this was not significant, p=0.138. We concluded that measurement of mandibular
      cortical width using active shape modeling is capable of diagnosing skeletal
      osteoporosis with good diagnostic ability and repeatability.

PMID- 17188598
TI  - Antenatal hormone exposures and SIDS.

PMID- 17188599
TI  - Transitioning HIV-infected children to adult care.

PMID- 17188601
TI  - FOPO, FOPE II and the future.

PMID- 17188602
TI  - Extreme pediatric obesity: weighing the health dangers.

PMID- 17188603
TI  - The vascular contribution to necrotizing enterocolitis.

PMID- 17188604
TI  - Recombinant human insulin-like growth factor I (rhIGF-I) and rhIGF-I/rhIGF
      binding-protein-3: new growth treatment options?

PMID- 17188605
TI  - Cardiovascular risk factors and excess adiposity among overweight children and
      adolescents: the Bogalusa Heart Study.
AB  - OBJECTIVE: To explore the accuracy of various body mass index (BMI) cutpoints in
      identifying children who have excess adiposity (based on skinfold thicknesses),
      adverse levels of lipids, insulin, and blood pressures, and a high risk for
      severe adult obesity. STUDY DESIGN: Cross-sectional (n = 10,099) and longitudinal
      (n = 2392) analyses were performed among subjects who participated in the
      Bogalusa Heart Study. RESULTS: Of children with a BMI > or =95th percentile (P)
      of the Centers for Disease Control (CDC) growth charts, 39% had at least two risk
      factors, 65% had excess adiposity, and 65% had an adult BMI of > or =35 kg/m(2).
      Of those with a BMI > or =99th P, 59% had at least two risk factors, 94% had
      excess adiposity, and 88% had an adult BMI of > or =35 kg/m(2). About 4% of
      children in the US now have a BMI > or =99th P. CONCLUSIONS: The 99th P of BMI
      for-age may be appropriate for identifying children who are at very high risk for
      biochemical abnormalities and severe adult obesity. More aggressive weight
      control strategies may be warranted for this subgroup.

PMID- 17188606
TI  - Childhood overweight and cardiovascular disease risk factors: the National Heart,
      Lung, and Blood Institute Growth and Health Study.
AB  - OBJECTIVE: To estimate the prevalence and incidence of overweight in African
      American and Caucasian girls, and to examine associations between adolescent
      overweight and cardiovascular disease (CVD) risk factors. STUDY DESIGN: In the
      National Heart, Lung and Blood Institute Growth and Health Study (NGHS), annual
      measurements were obtained from girls followed longitudinally between age 9 or 10
      and 18 years; self-reported measures were obtained at age 21 to 23 years. A total
      of 1166 Caucasian girls and 1213 African-American girls participated in the
      study. Childhood overweight as defined by the Centers for Disease Control and
      Prevention (CDC) was the independent variable of primary interest. Measured
      outcomes included blood pressure and lipid levels. RESULTS: Rates of overweight
      increased through adolescence from 7% to 10% in the Caucasian girls and from 17%
      to 24% in the African-American girls. The incidence of overweight was greater at
      age 9 to 12 than in later adolescence. Girls who were overweight during childhood
      were 11 to 30 times more likely to be obese in young adulthood. Overweight was
      significantly associated with increased percent body fat, sum of skinfolds and
      waist circumference measurements, and unhealthful systolic and diastolic blood
      pressure, high-density lipoprotein cholesterol, and triglyceride levels.
      CONCLUSION: A relationship between CVD risk factors and CDC-defined overweight is
      present at age 9.

PMID- 17188608
TI  - Cardiopulmonary exercise capacity, muscle strength, and physical activity in
      children and adolescents with achondroplasia.
AB  - OBJECTIVE: To study in children with achondroplasia the response to exercise and
      muscle strength compared with healthy peers and to describe the relation between
      exercise capacity, anthropometric factors, and physical activity. STUDY DESIGN:
      Patients (7 boys and 10 girls; mean age, 11.8 +/- 3.3 years) with achondroplasia
      performed a maximal treadmill exercise test. Anthropometric variables and muscle
      strength were measured and compared with the general population. The level of
      everyday physical activity was measured by using a diary. Functional ability was
      measured by using the Activity Scale for Kids. RESULTS: The exercise capacity of
      the children with achondroplasia was significantly reduced compared with
      reference values. All anthropometrical measurements differed significantly from
      reference values. There was a decrease in muscle strength in almost all muscle
      groups. We found a reduced physical activity level and impairments in functional
      ability. CONCLUSIONS: Cardiopulmonary exercise capacity and muscle strength in
      children with achondroplasia was reduced compared with reference values. Children
      with achondroplasia have a unique response to exercise. Clinicians should take
      these characteristic differences into account when the exercise capacity of
      subjects with achondroplasia is being tested.

PMID- 17188609
TI  - Pre-type 1 diabetes dysmetabolism: maximal sensitivity achieved with both oral
      and intravenous glucose tolerance testing.
AB  - OBJECTIVE: To determine the relationship of intravenous (IVGTT) and oral (OGTT)
      glucose tolerance tests abnormalities to diabetes development in a high-risk pre
      diabetic cohort and to identify an optimal testing strategy for detecting
      preclinical diabetes. STUDY DESIGN: Diabetes Prevention Trial-Type 1 Diabetes
      (DPT-1) randomized subjects to oral (n = 372) and parenteral (n = 339) insulin
      prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors
      associated with progression to diabetes were evaluated. RESULTS: Survival
      analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of
      first phase insulin response (FPIR) at baseline were associated with decreased
      diabetes-free survival. Cox proportional hazards modeling showed that baseline
      body mass index (BMI), FPIR, and 2-hour glucose levels were significantly
      associated with an increased hazard for diabetes. On testing performed within 6
      months of diabetes diagnosis, 3% (1/32) had normal FPIR and normal 2-hour glucose
      on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR
      performed within 6 months of diabetes diagnosis were equivalent (76% vs 73%).
      CONCLUSIONS: Most (97%) subjects had abnormal IVGTTs and/or OGTTs before the
      development of diabetes. The highest sensitivity is achieved using both tests.

PMID- 17188610
TI  - Rett syndrome and plasma leptin levels.
AB  - OBJECTIVE: To describe in patients with Rett syndrome (classic and preserved
      speech variant) plasma leptin levels and their relationship to BMI (body mass
      index) and age. STUDY DESIGN: Female patients (n = 48; age range 3-20 years)
      affected by classic Rett syndrome were enrolled into the study. Eleven female
      patients, age range 3 to 20 years, with preserved-speech variant Rett syndrome
      were included in the study. Controls were 24 healthy female subjects, age range 3
      to 20 years. Blood samples (3 mL) were withdrawn from an antecubital vein in the
      morning; plasma leptin concentrations were detected by enzyme-linked
      immunosorbent assay method. RESULTS: Patients with classic Rett syndrome and
      preserved-speech variant had leptin values significantly higher than controls.
      Leptin concentrations did not significantly differ between patients with classic
      Rett and preserved-speech variant. Leptin values positively correlated with age
      and BMI. CONCLUSIONS: Because in all patients the increased leptin concentrations
      were not associated to obesity, we hypothesize that in patients with Rett
      syndrome leptin might participate to clinical manifestations other than weight
      balance.

PMID- 17188611
TI  - Endothelial nitric oxide synthase in human intestine resected for necrotizing
      enterocolitis.
AB  - OBJECTIVE: To determine the expression and function of endothelial nitric oxide
      synthase (eNOS) in submucosal arterioles harvested from human intestine resected
      for necrotizing enterocolitis (NEC) or congenital bowel disease. STUDY DESIGN:
      eNOS expression was determined by using immunohistochemistry. The arteriolar
      diameter was measured in vitro at pressures of 10 to 40 mm Hg and also in
      response to the eNOS agonist acetylcholine (ACh), the exogenous nitric oxide (NO)
      donor S-nitroso-N-acetylpenicillamine, and the smooth muscle relaxant papaverine.
      Arteriolar release of NO in response to ACh was determined with a Sievers
      NOAnalyzer. Hemodynamics were also determined at flow rates of 50 and 100
      microL/min. RESULTS: eNOS was present in microvessels from both groups, but NEC
      arterioles failed to demonstrate physiological evidence of eNOS function: they
      constricted in response to pressure, failed to dilate or generate NO in response
      to ACh, and failed to dilate in response to flow. However, they dilated in
      response to exogenous NO and papaverine, indicating functional vascular smooth
      muscle and vasodilator reserve. CONCLUSION: eNOS-derived NO, a vasodilator in the
      newborn intestine, did not contribute to vasoregulation in arterioles harvested
      from intestine resected for NEC. These vessels were constricted; lack of eNOS
      derived NO may contribute to this vasoconstriction.

PMID- 17188614
TI  - Antenatal Doppler measurements and early brain injury in very low birth weight
      infants.
AB  - OBJECTIVE: To determine the correlation between fetoplacental blood flow and
      brain injury and volumes in very low birth weight (VLBW) infants. STUDY DESIGN:
      Antenatal blood flow from the umbilical artery (UA), middle cerebral artery
      (MCA), and descending aorta was determined in 70 VLBW infants. The directions of
      the total diastolic flow of the aortic isthmus and the end-diastolic flow of
      ductus venosus also were measured. Serial brain ultrasound examinations and MRI
      at term were performed to assess brain abnormalities. On the basis of brain
      imaging findings, the newborn infants were classified as normal (n = 14),
      intermediate brain pathology (n = 31), and major pathology (n = 25) groups.
      RESULTS: Abnormalities in fetoplacental blood flow were not related to anatomic
      brain lesions. However, an abnormal UA/MCA pulsatility index ratio was associated
      with reduced total brain volume (mean, 360 mL; SD, 32.5 mL) and reduced cerebral
      volume (344 mL; SD, 28.4 mL) compared with infants with normal UA/MCA pulsatility
      index ratio (mean, 405 mL; SD, 51.3 mL, P = .01, and mean, 368 mL; SD, 52.3 mL, P
      = .012), respectively. CONCLUSIONS: Redistribution of fetal blood flow in VLBW
      infants is associated with reduced brain volume at term age. Neurodevelopmental
      follow-up of this cohort will clarify the significance of these blood flow
      changes on development.

PMID- 17188612
TI  - Indomethacin prophylaxis for preterm infants: the impact of 2 multicentered
      randomized controlled trials on clinical practice.
AB  - OBJECTIVES: Two multicenter randomized controlled trials (RCTs) in premature
      infants (Ment et al, 1994 and TIPP, 2001) found beneficial effects of
      indomethacin prophylaxis on the incidences of patent ductus arteriosus (PDA), PDA
      ligation, and severe intracranial hemorrhage (ICH). The Ment trial recommended
      the use of indomethacin prophylaxis. The TIPP trial failed to find a benefit in
      its primary outcome (improved survival/neurodevelopmental outcome); this negative
      result may have discouraged indomethacin prophylaxis use. STUDY DESIGN: We used
      the National Institute of Child Health and Development's Neonatal Network
      Registry to determine the association between the 2 trials and the use of
      indomethacin prophylaxis. We also statistically assessed the assumptions that led
      to the TIPP trial's negative results. RESULTS: Use of indomethacin prophylaxis
      among network clinicians increased after publication of the Ment trial and
      decreased after the TIPP trial. Analysis of the TIPP trial showed that the
      primary outcome's anticipated effect size (> or = 20%) was too large; a smaller
      effect size (< 3%) would have been more appropriate based on the incidence of ICH
      in their population and its association with neurodevelopmental outcome.
      CONCLUSIONS: Two multicenter RCTs were associated with changes in indomethacin
      prophylaxis. After the Ment trial, the use of indomethacin prophylaxis increased.
      After the TIPP trial, which reported negative results based on an excessively
      large anticipated effect size, its use decreased.

PMID- 17188615
TI  - Lethal fetal and early neonatal presentation of adenylosuccinate lyase
      deficiency: observation of 6 patients in 4 families.
AB  - OBJECTIVE: To characterize a new lethal fetal and early postnatal variant of
      adenylosuccinate lyase (ADSL) deficiency. STUDY DESIGN: This was a retrospective
      analysis of 6 patients with very early presentation of ADSL deficiency. RESULTS:
      Most of the 6 patients had impaired intrauterine growth, microcephaly, fetal
      hypokinesia, and a lack of fetal heart rate variability. Postnatally, they shared
      severe muscular hypotonia necessitating mechanical ventilation, intractable
      seizures, and early death. All 6 patients had biochemical evidence of severe
      (type 1) disease and low residual ADSL activities. All were compound heterozygous
      for mutations that, based on expression studies, have a pronounced effect on ADSL
      activity and/or stability. CONCLUSIONS: ADSL deficiency may present with prenatal
      growth restriction, fetal and neonatal hypokinesia, and rapidly fatal neonatal
      encephalopathy. This clinical presentation is associated with genotypes resulting
      in very low residual enzyme activity.

PMID- 17188616
TI  - Thyroid morphology and subclinical hypothyroidism in children and adolescents
      with Williams syndrome.
AB  - OBJECTIVE: To verify the prevalence of morpho-volumetric and functional thyroid
      abnormalities in young patients with Williams syndrome (WS). STUDY DESIGN: Ninety
      two patients with WS (49 boys and 43 girls, 0.2-17.2 years of age) underwent
      evaluation of thyroid function by means of thyroid-stimulating hormone (TSH),
      fT3, and fT4 measurement. Thyroid ultrasonography was performed in 37 patients.
      Thyroid antibodies (thyroid peroxidase and thyroglobulin) were measured in all
      patients with abnormal thyroid function tests. RESULTS: None of our patients had
      overt hypothyroidism; 29 patients (31.5%) had subclinical hypothyroidism. Thyroid
      antibodies were absent in all patients. The prevalence of patients with
      subclinical hypothyroidism was significantly higher in the younger patients.
      Ultrasonography revealed morphological or volumetric abnormalities of the thyroid
      gland in 67.5% of patients; these abnormalities were more frequently observed in
      the older children. CONCLUSIONS: Subclinical hypothyroidism is a frequent but
      stable finding in young children with WS. The great majority of patients with WS
      >10 years, either with normal or hypoplastic thyroid, have normal thyroid
      function. Therefore, we suggest yearly monitoring of thyroid function and
      sonographic studies at least once in patients with WS. Treatment should be
      reserved for the patients with overt hypothyroidism or for those whose thyroid
      function shows signs of progressive deterioration.

PMID- 17188617
TI  - Somatic referral of visceral sensations and rectal sensory threshold for pain in
      children with functional gastrointestinal disorders.
AB  - OBJECTIVE: To test the hypothesis that abdominal pain related to functional
      gastrointestinal disorders is associated with visceral hypersensitivity and
      abnormal perception of visceral sensations. STUDY DESIGN: We examined 35 children
      (10-17.6 years old) fulfilling the Rome II criteria with irritable bowel syndrome
      (IBS; n = 21), functional abdominal pain (FAP; n = 8) or functional dyspepsia
      (FD; n = 6) compared with 10 control subjects (10.2-16.1 years). All underwent a
      rectal barostat examination. Painful sensations were reported on a human body
      diagram. The projections of sensations induced by rectal distension, the rectal
      sensory threshold for pain (RSTP) and the diagnostic value of RSTP measurements
      were measured. RESULTS: Rectal distension induced sensations that projected to
      the S3 dermatome in the control subjects and FD and to aberrant sites in children
      with IBS and FAP. The RSTP was decreased in children with IBS and FAP compared
      with control subjects (P <.002) and was not different in children with FD
      compared with control subjects. At 30.8 mm Hg, the 5th percentile for the control
      subjects, the RSTP had a sensitivity rate of 89% and a specificity rate of 83%
      for IBS and FAP diagnosis. CONCLUSION: Children with IBS and FAP are
      characterized by the association of rectal hypersensitivity and abnormal pain
      referral after rectal distension.

PMID- 17188618
TI  - Takayasu arteritis in children: preliminary experience with cyclophosphamide
      induction and corticosteroids followed by methotrexate.
AB  - OBJECTIVE: To review the results of our treatment protocol in the last 7 years.
      STUDY DESIGN: Six patients (4 girls, 2 boys) with an age range of 12 to 17 years
      were diagnosed with Takayasu arteritis (TA) during this period. Patients were
      allocated to receive (1) oral steroids and methotrexate (MTX) (12.5 mg/m(2)/week)
      if they had disease limited to one side of the diaphragm only without pulmonary
      disease involvement (two patients); and (2) oral steroids and oral
      cyclophosphamide (CYC) (maximum total dose 150 mg/kg) followed by oral MTX for
      maintenance as above if the disease was more widespread (four patients). RESULTS:
      One patient died of pulmonary vasculitis during the first month of therapy. The
      remaining three patients with involvement of both the thoracic and abdominal
      aorta and branches received the second protocol for 12 to 18 months. All entered
      remission. Aortic bypass, aortorenal bypass, balloon dilatation, and unilateral
      nephrectomy were performed in these patients. CONCLUSIONS: The presented single
      center experience suggests that CYC induction and corticosteroids followed by MTX
      is an effective and safe treatment for childhood TA.

PMID- 17188619
TI  - Beta-blocker therapy does not alter the rate of aortic root dilation in pediatric
      patients with Marfan syndrome.
AB  - OBJECTIVE: To test the hypothesis that chronic beta-blocker therapy in pediatric
      patients with Marfan syndrome alters the rate of aortic root dilation. Beta
      blockade has been advocated as preventive therapy for Marfan syndrome based on
      reports indicating a decreased rate of aortic root dilation in treated patients.
      STUDY DESIGN: Patients with Marfan syndrome (n = 63) followed at Children's
      Hospital of Pittsburgh or Children's Hospital of New York-Presbyterian who had >
      or =18 months of echocardiographic follow-up were studied. All clinical data and
      213 serial echocardiograms were reviewed, and aortic root dimensions were
      measured. Patients were divided into 2 groups for comparison: untreated (n = 34)
      and treated (n = 29). RESULTS: At study entry, the 2 study groups were comparable
      in terms of age, sex, body surface area (BSA), aortic root measurements, heart
      rate, and corresponding z scores. Follow-up duration in each group was similar.
      At last follow-up, heart rates and heart rate z scores were lower in the treated
      group. Rates of change of aortic root measurements (P = .52) and the
      corresponding z scores were not statistically different between the 2 group at
      the study's end. CONCLUSIONS: This study suggests that that beta-blocker therapy
      does not significantly alter the rate of aortic root dilation in children with
      Marfan syndrome. Based on these data, the recommendation of lifetime beta-blocker
      therapy instituted during childhood should be reassessed.

PMID- 17188625
TI  - Pediatric workforce: a look at adolescent medicine data from the American Board
      of Pediatrics.

PMID- 17188620
TI  - Bone mineral density in children and adolescents with neurofibromatosis type 1.
AB  - OBJECTIVE: To assess whether children and adolescents with neurofibromatosis type
      1 (NF1) have decreased bone mineral density (BMD). STUDY DESIGN: Bone
      densitometry of the whole body, hip, and lumbar spine was used in a case-to
      control design (84 individuals with NF1: 293 healthy individuals without NF1).
      Subjects were 5 to 18 years old. Subjects with NF1 were compared with control
      subjects by using an analysis-of-covariance with a fixed set of covariates (age,
      weight, height, Tanner stage, and sex). RESULTS: Subjects with NF1 had decreased
      areal BMD (aBMD) of the hip (P <.0001), femoral neck (P <.0001), lumbar spine (P
      = .0025), and whole body subtotal (P <.0001). When subjects with NF1 were
      separated in groups with and without a skeletal abnormality, those who did not
      have a skeletal abnormality still had statistically significant decreases in aBMD
      compared with control subjects (P <.0001 for whole body subtotal aBMD), although
      they were less pronounced than in those with osseous abnormalities. CONCLUSIONS:
      These data suggest that individuals with NF1 have a unique generalized skeletal
      dysplasia, predisposing them to localized osseous defects. Dual energy x-ray
      absorptiometry may prove useful in identifying individuals with NF1 who are at
      risk for clinical osseous complications and monitoring therapeutic trials.

PMID- 17188624
TI  - Does a normal DMSA obviate the performance of voiding cystourethrography in
      evaluation of young children after their first urinary tract infection?
AB  - OBJECTIVE: To determine whether a normal technetium-99m-labeled
      dimercaptosuccinic acid (DMSA) renal scan obviates the need for voiding
      cystourethrography (VCUG) in evaluating young children after their first urinary
      tract infection (UTI). STUDY DESIGN: This was a 10-year retrospective review of
      142 children (age < or = 2 years, 77 boys and 65 girls) who had their first UTI
      and were admitted to a tertiary care general hospital. The association between
      DMSA renal scan results and VCUG results performed 48 hours and 1 month after
      diagnosis was evaluated. RESULTS: DMSA renal scans and VCUG were performed in 142
      patients. Of these, 99 patients (69.7%) had evidence of pyelonephritis, although
      only 2 (1.4%) had evidence of renal scarring; 42 (29.6%) had vesicoureteral
      reflux (VUR) on VCUG. The sensitivity, specificity, positive and negative
      predictive values, and likelihood ratio negative for abnormalities on DMSA renal
      scans for detecting the the presence of VUR on VCUG were 88% (95% confidence
      interval [CI] = 73% to 100%), 36% (95% CI = 26% to 46%), 37% (95% CI = 27% to
      46%), 88 % (95% CI = 73% to 100%), and 0.33 (95% CI = 0 to 0.88), respectively.
      CONCLUSIONS: Children with a negative DMSA renal scan during their first UTI
      episode rarely have VUR and may never have high-grade VUR. Avoiding VCUGs in
      children with negative DMSA renal scans could significantly reduce the use of
      this potentially traumatic test.

PMID- 17188622
TI  - Procalcitonin to reduce the number of unnecessary cystographies in children with
      a urinary tract infection: a European validation study.
AB  - OBJECTIVE: To validate high serum procalcitonin (PCT) as a predictor of
      vesicoureteral reflux (VUR) in children with a first febrile urinary tract
      infection (UTI). STUDY DESIGN: This secondary analysis of prospective hospital
      based cohort studies included children ages 1 month to 4 years with a first
      febrile UTI. RESULTS: Of the 398 patients included in 8 centers in 7 European
      countries, 25% had VUR. The median PCT concentration was significantly higher in
      children with VUR than in those without: 1.6 versus 0.7 ng/mL (P = 10(-4)). High
      PCT (> or =0.5 ng/mL) was associated with VUR (OR: 2.3; 95% CI, 1.3 to 3.9; P =
      10(-3)). After adjustment for all cofactors, the association remained significant
      (OR: 2.5; 95% CI, 1.4 to 4.4; P = 10(-3)). The strength of the relation increased
      with the grade of reflux (P = 10(-5)). The sensitivity of procalcitonin was 75%
      (95% CI, 66 to 83) for all-grade VUR and 100% (95% CI, 81 to 100) for grade > or
      =4 VUR, both with 43% specificity (95% CI, 37 to 48). CONCLUSIONS: High PCT is a
      strong, independent and now validated predictor of VUR that can be used to
      identify low-risk patients and thus avoid one third of the unnecessary
      cystourethrographies in children with a first febrile UTI.

PMID- 17188626
TI  - A pilot trial in pediatrics with the sensor-augmented pump: combining real-time
      continuous glucose monitoring with the insulin pump.
AB  - Real-time continuous glucose monitoring and the insulin pump have been combined
      into the Sensor-Augmented Pump system (Medtronic MiniMed, Northridge, CA). This
      short-term pilot trial demonstrated that pediatric subjects with type I diabetes
      improved mean hemoglobin A1c (A1c) and glucose levels and reduced hypoglycemia
      and hyperglycemia using the Sensor-Augmented Pump system.

PMID- 17188629
TI  - Histopathologic abnormalities of the lymphoreticular tissues in organic cation
      transporter 2 deficiency: evidence for impaired B cell maturation.
AB  - Immunohistology of lymphoreticular tissues of a fatal case of organic cation
      transporter 2 deficiency revealed inhibited proliferation with increased
      apoptosis in the germinal centers, resulting in "burned out" follicles. This is
      indicative of impaired antigen driven B cell affinity maturation. Defective
      humoral immune response might explain the recurrent infections in untreated
      organic cation transporter 2 deficiency.

PMID- 17188630
TI  - Overcoiling of the umbilical cord.

PMID- 17188628
TI  - Association of interleukin-10 gene promoter polymorphism in children with atopic
      dermatitis.
AB  - The present study evaluated the possible role of interleukin (IL)-10 promoter
      polymorphisms in children with atopic dermatitis (AD). IL-10 promoter
      polymorphisms are associated with the phenotype of AD in children.

PMID- 17188637
TI  - TSDC spectroscopy of relaxational and interfacial phenomena.
AB  - Applications of thermally stimulated depolarisation current (TSDC) technique to a
      variety of systems with different dispersion phases such as disperse and porous
      metal oxides, polymers, liquid crystals, amorphous and crystalline solids,
      composites, solid solutions, biomacromolecules, cells, tissues, etc. in gaseous
      or liquid dispersion media are analysed. The effects of dipolar, direct current
      (dc) and space charge relaxations are linked to the temperature dependent
      mobility of molecules, their fragments, protons, anions, and electrons and depend
      on thermal treatment, temperature and field intensity of polarisation, heating
      rate on depolarisation or cooling rate on polarisation. Features of the
      relaxation mechanisms are affected not only by the mentioned factors but also by
      morphological, structural and chemical characteristics of materials. The
      interfacial phenomena, especially the role of interfacial water, received
      significant attention on analysis of the TSDC data. Comparison of the data of
      TSDC and dielectric relaxation spectroscopy (DRS), differential scanning
      calorimetry (DSC), 1H NMR spectroscopy with layer-by-layer freezing-out of bulk
      and interfacial water, adsorption/desorption of nitrogen, water and dissolved
      organics demonstrates high sensitivity and information content of the TSDC
      technique, allowing a deeper understanding of interfacial phenomena.

PMID- 17188638
TI  - A method for the isolation of blocked N-terminal peptides.

PMID- 17188639
TI  - Supporting the design of office layout meeting ergonomics requirements.
AB  - This paper proposes a method and an information technology tool aiming to support
      the ergonomics layout design of individual workstations in a given space
      (building). The proposed method shares common ideas with previous generic methods
      for office layout. However, it goes a step forward and focuses on the cognitive
      tasks which have to be carried out by the designer or the design team trying to
      alleviate them. This is achieved in two ways: (i) by decomposing the layout
      design problem to six main stages, during which only a limited number of
      variables and requirements are considered and (ii) by converting the ergonomics
      requirements to functional design guidelines. The information technology tool
      (ErgoOffice 0.1) automates certain phases of the layout design process, and
      supports the design team either by its editing and graphical facilities or by
      providing adequate memory support.

PMID- 17188640
TI  - The dual actions of angiogenesis and anti-apoptosis induced by an isolated
      fraction from Geum japonicum repair muscle ischemia.
AB  - The fundamental improvement of muscle ischemia requires the re-establishment of
      sufficient vessel network. Despite many kinds of drugs have been used for
      ischemia, effective angiogenic drug is very limited. Here, we reported the
      identification and isolation of a potent angiogenic fraction (angio-T) from Geum
      japonicum and assessment of its therapeutic effects on muscle ischemia by
      reconstituting the insufficient blood supply network and enhancing cell survival
      potential. It was demonstrated that angio-T not only significantly enhanced the
      proliferation of cultured HCAECs in vitro, but also significantly enhanced the
      survival potential of the myofibers at risk and neovascularization in ischemic
      muscles leading to reconstitution of these vessel networks, significant reduction
      of ischemic areas, and significant myofiber regeneration in ischemic area one
      week post-ischemia.

PMID- 17188642
TI  - Regulation of Clara cell secretory protein gene expression by the CCAAT-binding
      factor NF-Y.
AB  - Analysis of the transcriptional regulation of the Clara cell secretory protein
      (CCSP) gene has resulted in the characterization of several trans-acting factors
      that regulate the activity of this gene. However, little is known about negative
      regulatory elements involved in CCSP gene transcription. Using transient
      transfections of luciferase reporter constructs driven by various fragments of
      the Neotomodon CCSP (nCCSP) promoter, we identified an inhibitory region that
      contains an inverted CCAAT box located -225 to -221 bp upstream of the
      transcriptional start site. Sequence analysis in a broad region of the nCCSP
      promoter (-744/+33) identified another potentially important CCAAT motif (-459/
      455). Gel shift and supershift assays indicated that the transcription factor NF
      Y binds to both CCAAT boxes. Mutation of the CCAAT motif prevented the in vitro
      binding of NF-Y and led to a significant increase of CCSP promoter activity in
      both pulmonary (H441) and non-pulmonary (HeLa and MCF-7) cells, suggesting that
      NF-Y is involved in a negative transcriptional regulation that may potentially
      contribute to the highly cell-specific expression of the anti-inflammatory CCSP
      gene.

PMID- 17188641
TI  - Vertebrate and invertebrate carotenoid-binding proteins.
AB  - In invertebrates and vertebrates, carotenoids are ubiquitous colorants,
      antioxidants, and provitamin A compounds that must be absorbed from dietary
      sources and transported to target tissues where they are taken up and stabilized
      to perform their physiological functions. These processes occur in a specific and
      regulated manner mediated by high-affinity carotenoid-binding proteins. In this
      mini-review, we examine the published literature on carotenoid-binding proteins
      in vertebrate and invertebrate systems, and we report our initial purification
      and characterization of a novel lutein-binding protein isolated from liver of
      Japanese quail (Coturnix japonica).

PMID- 17188643
TI  - Cellular entry pathway and gene transfer capacity of TAT-modified lipoplexes.
AB  - Several reports have shown a fast and efficient translocation of TAT-modified
      lipoplexes and particles into the cell cytoplasm. However, neither the uptake
      mechanism nor the biological effect of TAT-modified lipoplexes has been studied
      in detail. In this report we show that the increase in gene transfer of TAT
      modified lipoplexes depends on the amount of cationic lipid in the lipoplexes and
      on the way TAT was coupled to the lipoplexes. We demonstrate that the cellular
      uptake of both TAT-modified and unmodified lipoplexes is very fast and, in
      contrast to previous publications, temperature-dependent. Additionally, after
      internalization TAT-modified as well as unmodified lipoplexes end up in lysosomal
      vesicles, indicating the involvement of clathrin-mediated endocytosis.
      Furthermore, chlorpromazine, a specific inhibitor of clathrin-dependent
      endocytosis, strongly inhibits the cellular uptake and biological activity of
      both the TAT-modified and unmodified lipoplexes. We also found that the uptake
      and biological activity of these lipoplexes are diminished when cholesterol in
      the cell membrane was bound by filipin, an inhibitor of the lipid-raft mediated
      pathway. Considering these data, we conclude that TAT-modified and unmodified
      lipoplexes are mainly internalized via a cholesterol-dependent clathrin-mediated
      pathway.

PMID- 17188644
TI  - NTS2 modulates the intracellular distribution and trafficking of NTS1 via
      heterodimerization.
AB  - Neurotensin (NT) receptors NTS1 and NTS2 are known to display considerable
      distributional overlap in mammalian central nervous system (CNS). Using co
      immunoprecipitation approaches, we demonstrated here that NTS1 forms constitutive
      heterodimers with NTS2 in transfected COS-7 cells. We also showed that co
      expression of NTS2 with NTS1 markedly decreases the cell surface density of NTS1
      without affecting ERK1/2 MAPK activity or NT-induced NTS1 internalization.
      However, radioligand-binding studies indicated that upon prolonged NT
      stimulation, cell surface NTS1 receptors are more resistant to down-regulation in
      cells co-expressing NTS1 and NTS2 than in cells expressing NTS1 alone. Taken
      together, these data suggest that NTS1/NTS2 heterodimerization affects the
      intracellular distribution and trafficking of NTS1 by making it more similar to
      that of NTS2 as witnessed in cells expressing NTS2 alone. NTS1/NTS2
      heterodimerization might therefore represent an additional mechanism in the
      regulation of NT-triggered responses mediated by NTS1 and NTS2 receptors.

PMID- 17188645
TI  - A novel function for alternative polyadenylation as a rescue pathway from NMD
      surveillance.
AB  - Premature termination codon (PTC) containing transcripts are subjected to a rapid
      degradation via nonsense-mediated decay (NMD) surveillance mechanism. By and
      large degradation is desired in order to prevent the translation of truncated,
      most likely deleterious, protein. Nevertheless, several dissimilar NMD-rescue
      events, capable of turning NMD-candidates into NMD-immune, are described. Yet,
      the extent and nature of this phenomenon is unknown. We screened the human genome
      for NMD-candidates transcripts. Among which we sub-grouped "pseudo-NMD" genes,
      which all their annotated transcripts contain PTCs, and therefore allegedly are
      transcribed but never translated. Here we show that alternative polyadenylation
      can rescue prematurely terminated transcripts, by truncating the pre-mRNA so that
      the PTC is now "legally" positioned. ESTs-based analysis shows that NMD-rescued
      genes are indeed expressed in human tissues. Furthermore, predicted NMD-rescue
      variants' existence is computationally verified. Hence, we suggest a novel role
      for the exon-truncated class of alternative polyadenylation as an NMD-rescue
      regulatory mechanism.

PMID- 17188646
TI  - Immunogenic gangliosides in human ovarian carcinoma.
AB  - Ganglioside signatures of four poorly and three moderately differentiated ovarian
      epithelial cancer (OEC) cell lines reveal the presence of GM3, GM2, GD2, O-AcGD2,
      GD1a and GM1b. The expression of GM3, presence of GD1a and GM1b in the ascitic
      fluid and plasma, together with a positive correlation in the total-gangliosides
      levels between ascitic fluid and plasma of OEC patients support the earlier
      contention that the tumor-gangliosides may be released (or shed) into the tumor
      microenvironment. The immunogenicity of OEC-gangliosides is determined by
      comparing anti-ganglioside-IgM titers in ascitic fluid (n = 14) and plasma (n =
      23) of OEC-patients and age-matched healthy (n = 14). The titers were measured by
      ELISA. Strikingly, the level of anti-GD1a-IgM is significantly higher in ascitic
      fluid and plasma of patients than in the plasma of healthy volunteers. Paired
      sample analysis of ascitic fluid and plasma from the same patients confirmed the
      significant expression of anti-GD1a IgM in OEC patients, while no such difference
      was observed with other anti-ganglioside IgMs among different groups. The
      significance of the endogenous IgM response to GD1a may be to eliminate this
      immunosuppressive-ganglioside from the tumor-microenvironment.

PMID- 17188648
TI  - Role of ionic interactions and linker in the domain interaction and modulation of
      functional activity of hyaluronate lyases.
AB  - Hyaluronate lyases from Streptococcus pneumoniae (SpnHL) and Streptococcus
      agalactiae (SagHL) are composed of four domains; N-terminal domain, spacer
      domain, alpha-domain and C-terminal domain, which are connected through peptide
      linkers. We have earlier shown that the recombinant alpha- and C-terminal domains
      of SpnHL/SagHL interact with each other even in absence of the linker and form a
      functional complex with enhanced enzymatic activity. Here, we looked into the
      role of ionic interactions in the enzyme stability and also the role of C
      terminal domain and linker in the functional regulation. Domain swapping studies
      showed that the C-terminal domain does not bind directly to the substrate;
      instead the domain contributes to the interaction with the polymeric hyaluronan
      for catalysis. Furthermore, the substrate specificity exchanges with the size of
      catalytic cleft. The role of linker connecting alpha-domain to C-terminal domain
      was found to hold the C-terminal domain in a conformation suitable for achieving
      maximum activity.

PMID- 17188647
TI  - Regionally selective effects of GABA on hypothalamic GABAA receptor mRNA in
      vitro.
AB  - We tested whether GABAA receptor (R) subunit mRNA levels are homeostatically
      influenced by short-term exposure to GABA in two adjacent regions of the
      posterior hypothalamus. mRNA levels for seven GABAAR subunits and GABA
      synthesizing enzyme (GAD) were quantified in the perifornical (PF) and
      dorsomedial (DM) hypothalamus following superfusion of slices for 90 min with a
      drug-free medium, GABA uptake blocker with or without GABAAR antagonist,
      gabazine, or GABAAR agonist with tetrodotoxin. Increasing endogenous GABA
      decreased mRNAs for all seven GABAAR subunits in the PF, and for three also in
      the DM, region; gabazine antagonized these effects in the PF region only and
      increased GAD-65 mRNA. Stimulation of GABAARs in the presence of tetrodotoxin
      decreased mRNA for one GABAAR subunit (beta1). We conclude that, in the PF region
      where GABA facilitates sleep, increased GABA release may limit GABAAR-mediated
      inhibition, whereas in the DM region, GABA-induced changes are mainly mediated by
      non-GABAA receptors.

PMID- 17188649
TI  - Assignment of the gene locus for severe congenital neutropenia to chromosome 1q22
      in the original Kostmann family from Northern Sweden.
AB  - Autosomal recessive severe congenital neutropenia (SCN) or Kostmann syndrome is
      characterised by reduced neutrophil counts and subsequent recurrent bacterial
      infections. The disease was originally described in a large consanguineous
      pedigree from Northern Sweden. A genome-wide autozygosity scan was initiated on
      samples from four individuals in the original pedigree using high density single
      nucleotide polymorphism (SNP) genotyping arrays in order to map the disease
      locus. Thirty candidate regions were identified and the ascertainment of samples
      from two additional patients confirmed a single haplotype with significant
      association to the disorder (p<0.01) on chromosome 1q22. One affected individual
      from the original Kostmann pedigree was confirmed as a phenocopy. The minimal
      haplotype shared by affected individuals spans a candidate region of 1.2 Mb,
      containing several potential candidate genes.

PMID- 17188650
TI  - Adrenodoxin supports reactions catalyzed by microsomal steroidogenic cytochrome
      P450s.
AB  - The interaction of adrenodoxin (Adx) and NADPH cytochrome P450 reductase (CPR)
      with human microsomal steroidogenic cytochrome P450s was studied. It is found
      that Adx, mitochondrial electron transfer protein, is able to support reactions
      catalyzed by human microsomal P450s: full length CYP17, truncated CYP17, and
      truncated CYP21. CPR, but not Adx, supports activity of truncated CYP19.
      Truncated and the full length CYP17s show distinct preference for electron donor
      proteins. Truncated CYP17 has higher activity with Adx compared to CPR. The
      alteration in preference to electron donor does not change product profile for
      truncated enzymes. The electrostatic contacts play a major role in the
      interaction of truncated CYP17 with either CPR or Adx. Similarly electrostatic
      contacts are predominant in the interaction of full length CYP17 with Adx. We
      speculate that Adx might serve as an alternative electron donor for CYP17 at the
      conditions of CPR deficiency in human.

PMID- 17188651
TI  - Abacavir modulates peroxynitrite-mediated oxidation of ferrous nitrosylated human
      serum heme-albumin.
AB  - Human serum albumin (SA) is best known for its extraordinary ligand-binding
      capacity. Here, kinetics of peroxynitrite-mediated oxidation of SA-heme(II)-NO is
      reported. Peroxynitrite reacts with SA-heme(II)-NO leading to SA-heme(III) and
      ()NO by way of the transient SA-heme(III)-NO species. Abacavir facilitates
      peroxynitrite-mediated oxidation of SA-heme(II)-NO, in the absence and presence
      of CO2. Values of the second order rate constant for peroxynitrite-mediated
      oxidation of SA-heme(II)-NO are (6.5+/-0.9) x 10(3) M(-1) s(-1) in the absence of
      CO2 and abacavir, (1.3+/-0.2) x 10(5) M(-1) s(-1) in the presence of CO2, (2.2+/
      0.2) x 10(4) M(-1) s(-1) in the presence of abacavir, and (3.6+/-0.3) x 10(5) M(
      1) s(-1) in the presence of both CO2 and abacavir. The value of the first-order
      rate constant for *NO dissociation from the SA-heme(III)-NO complex (=(1.8+/-0.3)
      x 10(-1) s(-1)) is CO2- and abacavir-independent, representing the rate-limiting
      step. Present data represent the first evidence for the allosteric modulation of
      SA-heme reactivity by heterotropic interaction(s).

PMID- 17188652
TI  - Functional studies on the activity of efflux transporters in an ex vivo model
      with chicken splenocytes and evaluation of selected fluoroquinolones in this
      model.
AB  - The efflux proteins P-glycoprotein (P-gp), BCRP and members of the MRP-family
      (MRPs) are increasingly recognized as determinants of the absorption, tissue
      distribution and excretion of numerous drugs. A widely applied in vitro screening
      method, to assess the effect of these efflux transporters in transmembrane
      transport of drugs is based on the use of peripheral blood mononuclear cells
      (PBMC), in which the efflux of fluorescent dye Rhodamine 123 (Rh-123) can be
      easily measured. In avian species, the isolation of PBMCs is compromised by the
      presence of thrombocytes having approximately the same size. As an alternative,
      we validated the use of isolated splenocytes to assess Rhodamine 123 transport in
      the presence and absence of specific inhibitors for P-gp, MRPs and BCRP. Rh-123
      efflux was concentration-dependent with the percentage of efflux that decreased
      with increasing concentrations. P-gp inhibitors, PSC833 and GF120918,
      significantly inhibit Rh-123 efflux, whereas inhibitors for MRPs and BCRP, MK571
      and Ko-143, respectively, have a limited inhibitory effect. However, the effect
      of GF120918 was more pronounced as compared to PSC833, suggesting an additional
      role for BCRP next to P-gp in Rh-123 efflux. Moreover, fluoroquinolones were
      selected to test the applicability of the described model. None of these
      fluoroquinolones significantly inhibit P-gp function at concentrations up to 50
      microM, with exception of danofloxacin and danofloxacin mesylate that were found
      to reduce Rh-123 efflux by approximately 15%.

PMID- 17188653
TI  - Vanadate-induced activation of cytosolic phospholipase A2alpha in L929 cells:
      Roles of tyrosine kinase, protein kinase C, and extracellular signal-regulated
      kinase.
AB  - Orthovanadate (Na3VO4), which acts as an inhibitor of protein tyrosine
      phosphatases, has a various pharmacological effects including the release of
      arachidonic acid (AA) from cells. We investigated roles of alpha-type cytosolic
      phospholipase A2 (cPLA2alpha), Src family kinases (Src) and protein kinase C
      (PKC) in the release of AA induced by Na3VO4 from a murine fibroblast cell line,
      L929. C12 cells, a variant of L929 that lacks expression of cPLA2alpha, were used
      along with a clone of C12 cells that are stably expressing cPLA2alpha (C12
      cPLA2alpha cells). In the presence of a Ca2+ ionophore (10 microM A23187), 5 and
      10mM Na3VO4 synergistically stimulated AA release from L929 and C12-cPLA2alpha
      cells, and to a much lesser extent from control C12 cells. The release of AA by
      Na3VO4/A23187 was inhibited by a selective cPLA2alpha inhibitor (3 microM
      pyrrophenone). The release of AA by Na3VO4/A23187 was significantly inhibited by
      a PKC inhibitor (10 microM GF109203X), in PKC-depleted cells, by a Src inhibitor
      (2 microM PP2) and by an inhibitor of extracellular signal-regulated kinase 1/2
      (ERK1/2) kinase (10 microM U0126). The phosphorylation of ERK1/2 was stimulated
      by Na3VO4, and the response was significantly decreased by inhibitors of Src, PKC
      and ERK1/2 kinase. Our data show that Na3VO4 stimulates AA release largely via
      cPLA2alpha activation in Ca2+-dependent manner, and the cross-talk between Src
      and PKC and the ERK-dependent pathways are involved in Na3VO4-induced AA release
      from L929 cells.

PMID- 17188654
TI  - Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the
      postmortem orbitofrontal cortex of patients with major depressive disorder.
AB  - BACKGROUND: Epidemiological surveys and peripheral tissue (red blood
      cells/plasma) fatty acid composition studies suggest that omega-3 fatty acid
      deficiency is associated with major depressive disorder (MDD) and suicide. It was
      hypothesized that patients with MDD would exhibit lower frontal cortical
      concentrations of docosahexaenoic acid (DHA), the principal omega-3 fatty acid in
      brain, relative to normal controls. METHODS: We determined the total fatty acid
      composition of postmortem orbitofrontal cortex (Brodmann's Area 10) from patients
      with DSM-IV-defined MDD (n = 15) and age-matched normal controls (n = 27) by gas
      chromatography. RESULTS: After correction for multiple comparisons, the omega-3
      fatty acid DHA was the only fatty acid that was significantly different (-22%) in
      the postmortem orbitofrontal cortex of MDD patients relative to normal controls.
      Deficits in DHA concentrations were greater in female MDD patients (-32%) than in
      male MDD patients (-16%), and could not be wholly attributed to lifestyle factors
      or postmortem tissue variables. CONCLUSIONS: These results demonstrate a
      selective deficit in the omega-3 fatty acid DHA in the orbitofrontal cortex of
      patients with MDD. This finding adds to a growing body of evidence implicating
      omega-3 fatty acid deficiency as well as the orbitofrontal cortex in the
      pathophysiology and potentially pathogenesis of MDD.

PMID- 17188655
TI  - Growth-deficient vomeronasal organs in the naked mole-rat (Heterocephalus
      glaber).
AB  - The naked mole-rat (Heterocephalus glaber) is unusual in numerous life history
      characteristics as well as its eusocial organization. This species demonstrates
      widespread sexual suppression and prominent scent marking, behaviors that have
      been associated with pheromonal communication involving the vomeronasal organ in
      other rodents. Yet, previous studies indicate that urinary signals do not mediate
      sexual suppression in Heterocephalus. Surprisingly, no previous studies have
      examined the vomeronasal organ in this species. Here, we show that Heterocephalus
      is unique among rodents in showing no evidence of postnatal volumetric growth in
      the vomeronasal neuroepithelium. Subadults from birth to weaning fell within the
      same volume range as adults regardless of breeding/non-breeding status of the
      latter. A comparison of existing ontogenetic data on other mammals suggests that
      the proportionally small VNOs of Heterocephalus may be explained by a deficiency
      in VNNE growth. Growth deficiency of the vomeronasal organ in Heterocephalus may
      relate to a diminished role that pheromones play in certain social interactions
      for this species, such as breeding suppression. In light of the unique aspects of
      the vomeronasal organ in Heterocephalus, comparative studies of rodents may
      provide a model for understanding variation of this sensory system in other
      mammalian orders including primates, an order which shows a range from vestigial
      to demonstrably functional vomeronasal organs.

PMID- 17188656
TI  - Validation of endogenous controls for quantitative gene expression analysis:
      application on brain cortices of human chronic alcoholics.
AB  - Real-time PCR is frequently used for gene expression quantification due to its
      methodological sensitivity and reproducibility. The gene expression is quantified
      by normalization to one or more reference genes, usually beta-actin (ACTB),
      glyceraldehyde-3-phosphate dehydrogenase (GAPD) or to ribosomal RNA (18S).
      However, different environmental or pathological conditions might also influence
      the expression of normalizing genes, which could severely skew the interpretation
      of quantitative results. This study evaluates whether 16 genes frequently used as
      endogenous controls in expression studies, can serve as such for comparison of
      human brain tissues of chronic alcoholics and control subjects. The prefrontal
      and motor cortices that are affected differently by chronic alcohol consumption
      were analyzed. The reference genes that have no or small differences in
      expression in alcoholics and control subjects, were found to be specific for each
      region: beta-actin (ACTB) and ribosomal large P0 (RPLP0) for the prefrontal
      cortex while importin 8 (IPO8) and RNA polymerase II (POLR2A) for the motor
      cortex. Four out of sixteen analyzed genes demonstrated significant differences
      in expression between alcoholics and controls: phosphoglycerate kinase (PGK1),
      hypoxanthine phosphoribosyl transferase (HPRT1) and peptidylprolyl isomerase A
      (PPIA) in the motor cortex and beta-2-microglobulin (B2M) in the prefrontal
      cortex. Our study demonstrates the importance of validation of endogenous control
      genes prior to real-time PCR analysis of human brain tissues. Prescribed and non
      prescribed drugs, pathological or environmental conditions along with alcohol
      abuse may differentially influence expression of reference genes.

PMID- 17188658
TI  - Cell death in rat cerebellar granule neurons induced by hydrogen peroxide in
      vitro: mechanisms and protection by adenosine receptor ligands.
AB  - Oxidative stress, resulting from excessive production of reactive oxygen species
      (ROS), is a pathological state that causes profound cellular damage and eventual
      death resulting from the overactivation of glutamate receptors, and the
      generation of nitric oxide, superoxide and hydrogen peroxide (H(2)O(2)). As such,
      H(2)O(2) represents an important model for studying the neuropathology of
      oxidative stress in a variety of CNS disorders. The effects of H(2)O(2) on the
      viability of post-natal cerebellar granule neurons (CGNs), the nature of the cell
      death involved and the potential protection by adenosine receptors against the
      damage were examined in the current study. Hydrogen peroxide (10-400 microM)
      reduced CGN viability in a concentration- and time-dependent manner. The addition
      of catalase (100 U/ml) prevented this effect, and the non-specific COX inhibitor
      aspirin (1 mM) also alleviated the damage. A combination of H(2)O(2) (5 microM)
      and Cu(2+) (0.5 mM) resulted in a significant damage that was not prevented by
      the hydroxyl radical scavenger mannitol (50 mM). The permeability transition pore
      blocker cyclosporin A, the caspase-3 inhibitor Z-DEVD-fmk (40 microM) and the
      PARP-1 inhibitor DPQ (10 microM) each significantly protected against peroxide
      damage. While the A(1) adenosine receptor agonist CPA and the A(2A) receptor
      antagonist ZM241385 (each at 100 nM) elicited protection, the A(1) adenosine
      receptor blocker DPCPX and the A(2A) receptor agonist CGS21680 (each at 100 nM)
      showed no effect. The data demonstrate that H(2)O(2) induced oxidative stress in
      CGNs, involving both apoptotic and necrotic death, and this can be ameliorated by
      A(1) receptor activation or A(2A) receptor blockade.

PMID- 17188657
TI  - Intranasal administration of E-selectin to induce immunological tolerization can
      suppress subarachnoid hemorrhage-induced vasospasm implicating immune and
      inflammatory mechanisms in its genesis.
AB  - Evidence that inflammatory and immune mechanisms may have a critical role in the
      development of vasospasm after subarachnoid hemorrhage is accumulating. We
      examined, therefore, whether induction of immunological tolerance to the adhesion
      molecule that is uniquely expressed on activated endothelium, E-selectin, could
      inhibit the vasospasm provoked by subarachnoid blood in a rat subarachnoid
      hemorrhage model. We found that intranasal instillation of E-selectin every other
      day for 10 days on a mucosal tolerization schedule suppressed delayed type
      hypersensitivity to E-selectin confirming tolerance to that molecule and markedly
      suppressed basilar artery spasm after subarachnoid hemorrhage. The results of
      this proof-of-concept study suggest that agents that can mimic the local effects
      of the mediators of mucosal tolerance could have therapeutic potential for the
      management of post-subarachnoid hemorrhage vasospasm.

PMID- 17188659
TI  - Retrograde labeling reveals extensive distribution of genioglossal motoneurons
      possessing 5-HT2A receptors throughout the hypoglossal nucleus of adult dogs.
AB  - Inspiratory hypoglossal motoneurons (IHMNs) innervate the muscles of the tongue
      and play an important role in maintaining upper airway patency. However, this may
      be reduced during sleep and by sedatives, potent analgesics, and volatile
      anesthetics. The genioglossal (GG) muscle is the main protruder and depressor
      muscle of the tongue and contributes to upper airway patency during inspiration.
      In vitro data suggest that serotonin (5-hydroxytryptamine, 5-HT), via the 5
      HT(2A) receptor (5-HT(2A)R) subtype, plays a key role in controlling the
      excitability of IHMNs. The distribution of GG motoneurons (GGMNs) within the
      hypoglossal (XII) nucleus has not been studied in the adult dog. Further, it is
      uncertain whether the 5-HT(2A)R is located on GGMNs in the adult dog. We
      therefore used the cholera toxin B (CTB) subunit as a retrograde tracer to map
      the location of GGMNs in combination with immunofluorescent labeling to determine
      the presence and colocalization of 5-HT(2A)R within the XII nucleus in adult
      mongrel dogs. Injection of CTB into the GG muscle resulted in retrogradely
      labeled cells in a compact column throughout the XII nucleus, extending from 0.75
      mm caudal to 3.45 mm rostral to the obex. Fluorescence immunohistochemistry
      revealed extensive 5-HT(2A)R labeling on CTB-labeled GGMNs. Identification of the
      5-HT(2A)R on GGMNs in the XII nucleus of the adult dog supports in vitro data and
      suggests a physiological role for this receptor subtype in controlling the
      excitability of GGMNs, which contribute to the maintenance of upper airway
      patency.

PMID- 17188660
TI  - Calretinin distribution in the octopus brain: an immunohistochemical and in situ
      hybridization histochemical analysis.
AB  - The distribution of calretinin containing neurons examined by in situ
      hybridization mapping was compared with that obtained by immunocytochemistry in
      the brain of octopus. Results revealed a close correspondence between the two
      types of investigations. Western blot analysis disclosed a 29 kDa protein
      immunostained with anti-calretinin antibody. Calretinin containing neurons were
      localized mainly in the cortex of octopus lobes, including the vertical, frontal,
      basal, buccal, palliovisceral, pedal and branchial, with variations of staining
      intensity and density of immunoreactive cells. The amacrine cells surrounding
      calretinin containing neuronal bodies of the cortex were also labeled unlike the
      glial cells. The close correspondence of blotting analysis, immunocytochemistry
      and in situ hybridization indicates with no doubt that calretinin, like other
      calcium-binding proteins previously studied, is also present in the nervous
      system of cephalopods. Furthermore, although recent findings localize calretinin
      also in endocrine glands, the presence of this calcium-binding protein in the
      brain of octopus indicates that calretinin appeared early in the phylogeny as a
      neuronal protein already in invertebrates.

PMID- 17188661
TI  - Auditory processing and learning/memory following erythropoietin administration
      in neonatally hypoxic-ischemic injured rats.
AB  - BACKGROUND: Hypoxia-ischemia (HI) is a common injury arising from
      prematurity/complications at birth and is associated with later language,
      auditory, and learning impairments. OBJECTIVE: To investigate the efficacy of two
      doses (300 or 1000 U/kg) of Erythropoietin (Epo) in protecting against
      neuropathological and behavioral impairments associated with HI injury in rats.
      METHODS: HI injury (right carotid artery cauterization and 120 min of 8% O(2))
      was induced on postnatal day 7 (P7) and Epo or saline was administered i.p.
      immediately following the procedure. Auditory processing and learning/memory were
      assessed throughout development. RESULTS: Both doses of Epo provided behavioral
      protection following HI injury. Rats given 300 or 1000 U/kg of Epo performed
      significantly better than HI animals on a short duration complex auditory
      processing procedure, on a spatial Morris water maze assessing spatial
      learning/reference memory, and a non-spatial water maze assessing associative
      learning/reference memory. CONCLUSIONS: Given Epo's extant clinical use (FDA
      approved for pediatric patients with anemia secondary to prematurity), the
      current results add to a growing body of literature supporting the use of Epo as
      a potential protective agent for neurological and behavioral impairments
      following early HI injury in infants.

PMID- 17188662
TI  - Increased 8-OHdG levels in the urine, serum, and substantia nigra of
      hemiparkinsonian rats.
AB  - 8-Hydroxy-2'-deoxyguanosine (8-OHdG), the predominant marker of oxidative DNA
      damage, may be a good biomarker for monitoring the progression of Parkinson's
      disease (PD). Unfortunately, there are no basic laboratory data examining 8-OHdG
      levels in animal models of PD. In this study, we demonstrate that rats lesioned
      with 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle display
      significantly elevated 8-OHdG levels in urine, serum, and substantia nigra, but
      not cerebrospinal fluid and striatum, compared to sham controls. These increments
      in 8-OHdG levels were detected at 2 days, but not at 7 days after the lesion
      suggesting that oxidative stress is restricted to the acute phase of 6-OHDA
      neurotoxicity. The present results support 8-OHdG as a biomarker that may aid
      both in the diagnosis and in the documentation of progression in PD.

PMID- 17188663
TI  - Cell cycle inhibition attenuates microglia induced inflammatory response and
      alleviates neuronal cell death after spinal cord injury in rats.
AB  - The spinal cord is well known to undergo inflammatory reactions in response to
      traumatic injury. Activation and proliferation of microglial cells, with
      associated proinflammatory cytokines expression, plays an important role in the
      secondary damage following spinal cord injury. It is likely that microglial cells
      are at the center of injury cascade and are targets for treatments of CNS
      traumatic diseases. Recently, we have demonstrated that the cell cycle inhibitor
      olomoucine attenuates astroglial proliferation and glial scar formation,
      decreases lesion cavity and mitigates functional deficits after spinal cord
      injury (SCI) in rats [Tian, D.S., Yu, Z.Y., Xie, M.J., Bu, B.T., Witte, O.W.,
      Wang, W., 2006. Suppression of astroglial scar formation and enhanced axonal
      regeneration associated with functional recovery in a spinal cord injury rat
      model by the cell cycle inhibitor olomoucine. J. Neurosci. Res. 84, 1053-1063].
      Whether neuroprotective effects of cell cycle inhibition are involved in
      attenuation of microglial induced inflammation awaits to be elucidated. In the
      present study, we sought to determine the influence of olomoucine on microglial
      proliferation with associated inflammatory response after spinal cord injury.
      Tissue edema formation, microglial response and neuronal cell death were
      quantified in rats subjected to spinal cord hemisection. Microglial proliferation
      and neuronal apoptosis were observed by immunofluorescence. Level of the
      proinflammatory cytokine interleukin-1beta (IL-1beta) expression in the injured
      cord was determined by Western blot analysis. Our results showed that the cell
      cycle inhibitor olomoucine, administered at 1 h post injury, significantly
      suppressed microglial proliferation and produced a remarkable reduction of tissue
      edema formation. In the olomoucine-treated group, a significant reduction of
      activated and/or proliferated microglial induced IL-1beta expression was observed
      24 h after SCI. Moreover, olomoucine evidently attenuated the number of apoptotic
      neurons after SCI. Our findings suggest that modulation of microglial
      proliferation with associated proinflammatory cytokine expression may be a
      mechanism of cell cycle inhibition-mediated neuroprotections in the CNS trauma.

PMID- 17188664
TI  - Angiogenesis and improved cerebral blood flow in the ischemic boundary area
      detected by MRI after administration of sildenafil to rats with embolic stroke.
AB  - To dynamically investigate the long-term response of an ischemic lesion in rat
      brain to the administration of sildenafil, male Wistar rats subjected to embolic
      stroke were treated with sildenafil (n=11) or saline (n=10) at a dose of 10 mg/kg
      administered subcutaneously 24-h after stroke and daily for an additional 6 days.
      Magnetic resonance images were acquired and functional performance was measured
      in all animals at 1 day, 2 days and weekly for 6 weeks post-stroke. All rats were
      sacrificed 6 weeks after stroke and endothelial barrier antigen immunostaining
      was employed for morphological analysis and quantification of cerebral vessels.
      Map-ISODATA was computed from T(1), T(2) and T(1sat) maps. ISODATA derived tissue
      signatures characterize the degree of ischemic injury. Based on the map-ISODATA
      calculated at 6 weeks, the ischemic lesion for each animal was divided into two
      specific regions, the ischemic boundary and ischemic core. The temporal profiles
      of cerebral blood flow (CBF) and tissue signature were retrospectively tracked in
      these two regions and were compared with histological evaluation and functional
      outcome. After 1 week of sildenafil treatment, the ischemic lesion exhibited two
      significantly different regions, with higher CBF level and correspondingly, lower
      tissue signature value in the boundary region than in the core region. Sildenafil
      treatment did not significantly reduce the lesion size, but did enhance
      angiogenesis. Functional performance was significantly increased after sildenafil
      treatment compared with the control group. Administration of sildenafil to rats
      with embolic stroke enhances angiogenesis and selectively increases the CBF level
      in the ischemic boundary, and improves neurological functional recovery compared
      to saline-treated rats.

PMID- 17188665
TI  - The influence of cervical spinal cord stimulation on induced epileptic discharges
      in rats.
AB  - Spinal cord stimulation (SCS), also known as dorsal column stimulation, is a
      novel technique used widely in pain surgery. However, its effect on other
      pathologies such as epileptic disorders is unknown. The aim of this study is to
      evaluate the influence of electrical epidural stimulation of the upper cervical
      region on epileptic cortical discharges. The long term goal is to elucidate and
      evaluate a therapeutic central nervous system (CNS) electrical stimulation
      methodology to treat epilepsy. Twelve Wistar female rats were randomly divided
      into two groups. In group 1 (six rats under general anesthesia), C2-3
      laminectomies were performed and epidural electrodes were placed to perform SCS.
      To induce epileptic discharges, 1 ml (200 IU) penicillin G was microinjected into
      the left somatomotor cortex via left stereotactic parietal craniotomies, 0.01 to
      0.1 mA at 2 Hz was used to stimulate the spinal cord. In group 2 (the control
      group, six rats under general anesthesia), C2-3 laminectomies were performed
      without electrode placement and epileptic discharges were induced with penicillin
      G microinjections, as described above. Both groups were monitored with digital
      electroencencephalography (EEG) for 70 min in seven stages and recordings
      analyzed with power spectral analysis. Spinal cord stimulation decreased
      penicillin-induced median values of epileptic discharges. Epileptic wave
      frequencies decreased significantly with increasing intensities of SCS. The
      results of this study suggest that SCS used for drug resistant epilepsies may be
      a viable alternative treatment modal.

PMID- 17188666
TI  - The inotropic adaptation during late preconditioning against myocardial stunning
      is associated with an increase in FKBP12.6.
AB  - The inotropic adaptation during late preconditioning against myocardial stunning
      is associated with an increase in FKBP12.6. by Laurence Lucats, Laurent Vinet,
      Alain Bize, Xavier Monnet, Didier Morin, Jin Bo Su, Patricia Rouet-Benzineb,
      Olivier Cazorla, Jean-Jacques Mercadier, Luc Hittinger, Alain Berdeaux, Bijan
      Ghaleh. OBJECTIVES: Late preconditioning reduces contractile dysfunction during
      myocardial stunning. Mechanisms involving adaptation of calcium handling during
      excitation-contraction coupling to late preconditioning remain to be established.
      Thus, we investigated whether the late preconditioned myocardium is associated
      with contractile adaptation and changes in the cardiac ryanodine receptor (RyR2)
      and its regulatory protein FKBP12.6. METHODS: Chronically instrumented conscious
      dogs (coronary occluder, ultrasonic crystals for sonomicrometry) underwent a 10
      min coronary artery occlusion followed by reperfusion. They were studied 24 h
      later in the late preconditioned state (day 1). RESULTS: Maximal velocity of wall
      thickening at day 1 was increased as compared to corresponding baseline at day 0
      (39+/-4 vs. 30+/-3 mm/s, p < 0.05) although systolic wall thickening was similar
      (2.8+/-0.2 vs. 2.9+/-0.2 mm), demonstrating a significant change in left
      ventricular inotropic state. Intracoronary infusion of ryanodine (0.5-6 microg)
      induced a dose-dependent decrease in wall thickening. In the late preconditioned
      state, this negative inotropic response was significantly reduced vs. control
      state, suggesting changes in sarcoplasmic reticulum (SR) Ca2+-release through
      RyR2. Immunoquantification of FKBP12.6 revealed a 2.8 fold ventricular increase
      after late preconditioning as compared to the control state. The amount of RyR2
      and its phosphorylated state were similar and binding experiments did not reveal
      any alterations in B(max) or K(D) for RyR2. Calsequestrin, SERCA2a and
      phospholamban levels were not altered by late preconditioning. CONCLUSIONS: The
      late preconditioned myocardium is characterized by an adaptation of regional
      function associated with an increased expression of FKBP12.6. This demonstrates
      an adaptation of the SR Ca2+-release through RyR2 during late preconditioning.

PMID- 17188667
TI  - TRPM4, a Ca2+-activated nonselective cation channel in mouse sino-atrial node
      cells.
AB  - OBJECTIVE: A calcium-activated nonselective cation channel (NSC(Ca)) has been
      recently described in several cardiac preparations. This channel is over
      expressed in models of ventricular hypertrophy showing electrophysiological
      perturbations of heart activity, including occurrence of spontaneous activity.
      While these perturbations are currently attributed to a modification of the
      pacemaker I(f) current activity, arguments are also in favor of participation of
      an NSC(Ca). Similarly, the NSC(Ca) may be expressed in specialized pacemaker
      cells, i.e. sino-atrial node (SAN) cells. The aim of the present study was to
      detect such current in mouse pacemaker cells. METHODS: The inside-out
      configuration of the patch-clamp technique was used in freshly isolated SAN cells
      from adult mice. Also, RT-PCR and Western-blotting studies were used to probe for
      TRPM4 mRNA and protein expression. RESULTS: In these cells, an NSC(Ca) activity
      was detected. The channel is voltage dependant with a conductance of 20.9+/-0.5
      pS (n = 11). It is equally permeable for Na+ and K+ but does not conduct Ca2+. It
      is activated by rise in intracellular calcium concentrations and blocked by
      intracellular ATP (0.5 mmol/L). Also, as a new property in cardiac cells, the
      channel is activated by internal application of phosphatidylinositol 4,5
      bisphosphate (10 microM). It is reversibly inhibited by flufenamic acid and
      glibenclamide. This channel shows the hallmarks of the TRPM4 molecule, a member
      of the TRP melastatin subfamily. We confirm the expression of this TRP channel on
      SAN cells by Western blotting and RT-PCR and validate that TRPM4 is glibenclamide
      sensitive. CONCLUSION: TRPM4 is functionally expressed in SAN cells and may be a
      key player in the generation and/or perturbation of heart rhythm.

PMID- 17188668
TI  - Surgical animal models of heart failure related to coronary heart disease.
AB  - Coronary heart disease is caused by atherosclerotic narrowing of coronary
      arteries. It accounts for about two-thirds of heart failure cases, which are
      frequently secondary to myocardial infarction. Despite considerable progress in
      the understanding and management of heart failure, its incidence, prevalence and
      economic burden are steadily increasing. Therefore, efficient preventive and
      therapeutic measures are urgently needed. In order to investigate the mechanisms
      involved in the pathogenesis of coronary heart disease-related heart failure and
      to develop therapies, appropriate animal models are indispensable. According to
      the aetiology of this disorder, surgical models are based on various methods
      allowing for the narrowing or occlusion of coronary arteries. Depending on the
      duration and extent of the impairment of coronary blood flow and its consequences
      for cardiac tissue, these are classified as models of myocardial infarction,
      cardiac ischemia/reperfusion injury, or chronic cardiac ischemia. In addition,
      factors such as species, strain, and gender of the laboratory animals also
      significantly contribute to the pathophysiology of the induced disorder and,
      therefore, have to be taken into consideration thoroughly when an animal model is
      to be established.

PMID- 17188669
TI  - Interleukin-10 is not a critical regulator of infarct healing and left
      ventricular remodeling.
AB  - OBJECTIVE: Interleukin-10 (IL-10) exerts potent anti-inflammatory actions and
      modulates matrix metalloproteinase expression. We hypothesized that endogenous IL
      10 may regulate infarct healing and left ventricular remodeling by promoting
      resolution of the post-infarction inflammatory response and by modulating
      extracellular matrix metabolism. METHODS: IL-10 null and wildtype (WT) mice
      underwent reperfused infarction protocols. We compared the healing response and
      remodeling-associated parameters between IL-10-/-and WT infarcts. In addition, we
      studied the effects of IL-10 on inflammatory gene synthesis by stimulated murine
      cardiac fibroblasts. RESULTS: Infarcted IL-10-/-mice exhibited comparable
      mortality rates with WT animals. Although IL-10-/-mice had higher peak tumor
      necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1/CCL2
      mRNA levels in the infarcted heart than WT mice, both groups demonstrated timely
      repression of pro-inflammatory cytokine and chemokine mRNA synthesis after 24 h
      of reperfusion and exhibited a similar time course of resolution of the
      neutrophil infiltrate. IL-10 gene disruption did not alter fibrous tissue
      deposition and dilative remodeling of the infarcted heart. Pre-incubation with IL
      10 did not modulate the pro-inflammatory phenotype of TNF-alpha-stimulated
      cardiac fibroblasts, failing to inhibit chemokine mRNA synthesis. In contrast,
      transforming growth factor (TGF)-beta1 pre-incubation suppressed interferon-gamma
      inducible protein (IP)-10/CXCL10 synthesis by cardiac fibroblasts exposed to TNF
      alpha. CONCLUSIONS: IL-10 signaling plays a non-critical role in suppression of
      inflammatory mediators, resolution of the inflammatory response, and fibrous
      tissue deposition following myocardial infarction. This may be due to the
      relative selectivity of IL-10-mediated anti-inflammatory actions, with respect to
      cell type and stimulus. Resolution of post-infarction inflammation is likely to
      involve multiple overlapping regulatory mechanisms controlling various pro
      inflammatory pathways activated in the infarcted myocardium.

PMID- 17188670
TI  - Beneficial effects of Murraya koenigii leaves on antioxidant defense system and
      ultra structural changes of pancreatic beta-cells in experimental diabetes in
      rats.
AB  - Oxidative stress and oxidative damage to tissues are common end points of chronic
      diseases such as atherosclerosis, diabetes, and rheumatoid arthritis. Oxidative
      stress in diabetes coexists with a reduction in the antioxidant status, which can
      further increase the deleterious effects of free radicals. The aim of the present
      study was to evaluate the possible protective effects of Murraya koenigii leaves
      extract against beta-cell damage and antioxidant defense systems of plasma and
      pancreas in streptozotocin induced diabetes in rats. The levels of glucose and
      glycosylated hemoglobin in blood and insulin, Vitamin C, Vitamin E,
      ceruloplasmin, reduced glutathione and TBARS were estimated in plasma of control
      and experimental groups of rats. To assess the changes in the cellular
      antioxidant defense system such as the level of reduced glutathione and
      activities of superoxide dismutase, catalase and glutathione peroxidase were
      assayed in pancreatic tissue homogenate. The levels of glucose, glycosylated
      hemoglobin, insulin, TBARS, enzymatic and non-enzymatic antioxidants were altered
      in diabetic rats. These alterations were reverted back to near control levels
      after the treatment of M. koenigii leaves extract. Transmission electron
      microscopic studies also revealed the protective nature of M. koenigii leaves on
      pancreatic beta-cells. These findings suggest that M. koenigii treatment exerts a
      therapeutic protective nature in diabetes by decreasing oxidative stress and
      pancreatic beta-cell damage. The antioxidant effect of the M. koenigii extract
      was compared with glibenclamide, a well-known hypoglycemic drug.

PMID- 17188671
TI  - Oxalate modulates thiobarbituric acid reactive species (TBARS) production in
      supernatants of homogenates from rat brain, liver and kidney: effect of diphenyl
      diselenide and diphenyl ditelluride.
AB  - The aim of this paper was to investigate the mechanism(s) involved in the sodium
      oxalate pro-oxidative activity in vitro and the potential protection by diphenyl
      diselenide ((PhSe)(2)) and diphenyl ditelluride ((PhTe)(2)) using supernatants of
      homogenates from brain, liver and kidney. Oxalate causes a significant increase
      in the TBARS (thiobarbituric acid reactive species) production up to 4mmol/l and
      it had antioxidant activity from 8 to 16mmol/l in the brain and liver. Oxalate
      had no effect in kidney homogenates. The difference among tissues may be related
      to the formation of insoluble crystal of oxalate in kidney, but not in liver and
      brain homogenates. (PhSe)(2) and (PhTe)(2) reduced both basal and oxalate-induced
      TBARS in rat brain homogenates, whereas in liver homogenates they were
      antioxidant only on oxalate-induced TBARS production. (PhSe)(2) showed a modest
      effect on renal TBARS production, whereas (PhTe)(2) did not modulate TBARS in
      kidney preparations. Oxalate at 2mmol/l did not change deoxyribose degradation
      induced by Fe(2+) plus H(2)O(2), whereas at 20mmol/l it significantly prevents
      its degradation. Oxalate (up to 4mmol/l) did not alter iron (10micromol/l)
      induced TBARS production in the brain preparations, whereas at 8mmol/l onwards it
      prevents iron effect. In liver preparations, oxalate amplifies iron pro-oxidant
      activity up to 4mmol/l, preventing iron-induced TBARS production at 16mmol/l
      onwards. These results support the antioxidant effect of organochalcogens against
      oxalate-induced TBARS production. In addition, our results suggest that oxalate
      pro- and antioxidant activity in vitro could be related to its interactions with
      iron ions.

PMID- 17188672
TI  - A human hepatocellular in vitro model to investigate steatosis.
AB  - The present study was designed to define an experimental model of hepatocellular
      steatosis with a fat overaccumulation profile in which the metabolic and
      cytotoxic/apoptotic effects could be separated. This was accomplished by defining
      the experimental conditions of lipid exposure that lead to significant
      intracellular fat accumulation in the absence of overt cytotoxicity, therefore
      allowing to differentiate between cytotoxic and apoptotic effects. Palmitic
      (C16:0) and oleic (C18:1) acids are the most abundant fatty acids (FFAs) in liver
      triglycerides in both normal subjects and patients with nonalcoholic fatty liver
      disease (NAFLD). Therefore, human hepatocytes and HepG2 cells were incubated with
      a mixture of different proportions of saturated (palmitate) and unsaturated
      (oleate) FFAs to induce fat-overloading. Similar intracellular levels of lipid
      accumulation as in the human steatotic liver were achieved. Individual FFAs have
      a distinct inherent toxic potential. Fat accumulation, cytotoxicity and apoptosis
      in cells exposed to the FFA mixtures were investigated. The FFA mixture
      containing a low proportion of palmitic acid (oleate/palmitate, 2:1 ratio) is
      associated with minor toxic and apoptotic effects, thus representing a cellular
      model of steatosis that mimics benign chronic steatosis. On the other hand, a
      high proportion of palmitic acid (oleate/palmitate, 0:3 ratio) might represent a
      cellular model of steatosis in which saturated FFAs promote an acute harmful
      effect of fat overaccumulation in the liver. These hepatic cellular models are
      apparently suitable to experimentally investigate the impact of fat
      overaccumulation in the liver excluding other factors that could influence
      hepatocyte behaviour.

PMID- 17188673
TI  - Imaging of the domain organization in sphingomyelin and phosphatidylcholine
      monolayers.
AB  - The lateral organization of biomembranes has gained significant interest when the
      fluid mosaic model was challenged by the model of "lipid rafts". Several lipid
      classes like cholesterol and sphingolipids are considered to be essential for
      their formation. Here we investigate the lateral domain formation in binary
      mixtures of sphingomyelin and phosphatidylcholine. Both are major lipid
      components of lipoproteins and mammalian cell membranes at various molar ratios.
      Surface pressure-area isotherms and surface potential-area isotherms of
      monolayers composed of these lipids clearly indicated non-ideal mixing. In
      addition, Brewster angle microscopy provided a well-suited approach to image the
      formation of lateral domains. These images demonstrated that pure sphingomyelin
      forms very stable finger-like domains that exhibit a distinct internal
      organization suggesting an anisotropic orientation of the acyl side chains.
      Similar behavior was found for mixtures containing more than 60 mol%
      sphingomyelin. With increasing content of phosphatidylcholine the domain size
      decreased and the surface pressure, where domain formation occurred, increased.
      At lower sphingomyelin content (30-60 mol%) rather round-shaped, smaller domains
      were observed. Thus, the potential of sphingomyelin domains as potentially
      important building blocks for actual domains that could be building blocks for
      raft formation is suggested, even without the presence of cholesterol. In
      addition, these observations may suggest a role for the distinct molar ratio of
      these key lipids frequently found in physiologically relevant particles such as
      low and high density lipoproteins or the outer leaflet of the human erythrocyte
      membrane.

PMID- 17188674
TI  - Relationship of apolipoprotein A5 and apolipoprotein C3 levels to serum
      triglycerides in patients with type 2 diabetes.
AB  - BACKGROUND: The role of apolipoprotein A5 (ApoA5) in modulating triglyceride
      levels in humans is incompletely understood. Some researchers have reported
      modest positive correlations of ApoA5 with triglycerides while others have
      reported negative correlations. A recent report suggested that ApoA5 gene
      expression may be influenced by insulin. In type 2 diabetes, some groups have
      reported higher levels of ApoA5 compared to normals while others have reported
      lower levels. METHODS: To better understand the relationships between ApoA5,
      apolipoprotein C3 (ApoC3), and triglycerides in type 2 diabetes, ApoA5 levels
      were measured and correlated with triglyceride, insulin, and HbA1c levels. ApoC3
      levels were measured and correlated with triglycerides. RESULTS: In patients with
      type 2 diabetes, ApoA5 levels were elevated compared to normals, with several
      patients having markedly increased levels confirmed by Western blotting. ApoA5
      levels were positively correlated with triglycerides (r=0.60) but were not
      correlated with either HbA1c or serum insulin levels. ApoC3 levels were highly
      positively correlated with triglycerides (r=0.88). CONCLUSIONS: These data
      indicate that in patients with type 2 diabetes ApoA5 levels are positively
      correlated with triglycerides but are not correlated with HbA1c or insulin
      levels. ApoC3 levels are strongly positively correlated with triglycerides in
      these patients.

PMID- 17188675
TI  - Modification of tandem mass spectrometric method to permit simultaneous
      quantification of 17 anti-HIV drugs which include atazanavir and tipranavir.

PMID- 17188676
TI  - Dog is a dog is a dog: infant rule learning is not specific to language.
AB  - Human infants possess powerful learning mechanisms used for the acquisition of
      language. To what extent are these mechanisms domain specific? One well-known
      infant language learning mechanism is the ability to detect and generalize rule
      like similarity patterns, such as ABA or ABB [Marcus, G. F., Vijayan, S., Rao, S.
      B., & Vishton, P. M. (1999). Rule learning by seven-month-old infants. Science,
      283, 77-80.]. The results of three experiments demonstrate that 7-month-old
      infants can detect and generalize these same patterns when the elements consist
      of pictures of animals (dogs and cats). These findings indicate that rule
      learning of this type is not specific to language acquisition.

PMID- 17188677
TI  - Polygon interpolation for serial cross sections.
AB  - In this paper, a new technique for contour interpolation between slices is
      presented. We assumed that contour interpolation is equivalent to the
      interpolation of a polygon that approximates the object shape. The location of
      each polygon vertex is characterized by a set of parameters. Polygon
      interpolation can be performed on these parameters. These interpolated parameters
      are then used to reconstruct the vertices of the new polygon. Finally, the
      contour is approximated from this polygon using a cubic spline interpolation.
      This new technique takes into account the shape, the translation, the size, and
      the orientation of the object's contours. A comparison with regular shape-based
      interpolation is made on several object contours. The preliminary results show
      that this new method yields a better contour and is computationally more
      efficient than shape-based interpolation. This technique can be applied to gray
      level images too. The interpolation result of an MR image does not show artifact
      of intermediate substance commonly seen in a typical linear gray-level
      interpolation.

PMID- 17188678
TI  - Chemosensitivity of primary human fibroblasts with defective unhooking of DNA
      interstrand cross-links.
AB  - Xeroderma pigmentosum (XP) is characterised by defects in nucleotide excision
      repair, ultraviolet (UV) radiation sensitivity and increased skin carcinoma.
      Compared to other complementation groups, XP-F patients show relatively mild
      cutaneous symptoms. DNA interstrand cross-linking agents are a highly cytotoxic
      class of DNA damage induced by common cancer chemotherapeutics such as cisplatin
      and nitrogen mustards. Although the XPF-ERCC1 structure-specific endonuclease is
      required for the repair of ICLs cellular sensitivity of primary human XP-F cells
      has not been established. In clonogenic survival assays, primary fibroblasts from
      XP-F patients were moderately sensitive to both UVC and HN2 compared to normal
      cells (2- to 3-fold and 3- to 5-fold, respectively). XP-A fibroblasts were
      considerably more sensitive to UVC (10- to 12-fold) but not sensitive to HN2. The
      sensitivity of XP-F fibroblasts to HN2 correlated with the defective incision or
      'unhooking' step of ICL repair. Using the comet assay, XP-F cells exhibited only
      20% residual unhooking activity over 24 h. Over the same time, normal and XP-A
      cells unhooked greater than 95% and 62% of ICLs, respectively. After HN2
      treatment, ICL-associated DNA double-strand breaks (DSBs) are detected by pulse
      field gel electrophoresis in dividing cells. Induction and repair of DNA DSBs was
      normal in XP-F fibroblasts. These findings demonstrate that in primary human
      fibroblasts, XPF is required for the unhooking of ICLs and not for the induction
      or repair of ICL-associated DNA DSBs induced by HN2. In terms of cancer
      chemotherapy, people with mild DNA repair defects affecting ICL repair may be
      more prevalent in the general population than expected. Since cellular
      sensitivity of primary human fibroblasts usually reflects clinical sensitivity
      such patients with cancer would be at risk of increased toxicity.

PMID- 17188679
TI  - Alterations in immunological and neurological gene expression patterns in
      Alzheimer's disease tissues.
AB  - Microarray technology was utilized to isolate disease-specific changes in gene
      expression by sampling across inferior parietal lobes of patients suffering from
      late onset AD or non-AD-associated dementia and non-demented controls. Primary
      focus was placed on understanding how inflammation plays a role in AD
      pathogenesis. Gene ontology analysis revealed that the most differentially
      expressed genes related to nervous system development and function and
      neurological disease followed by genes involved in inflammation and immunological
      signaling. Pathway analysis also implicated a role for chemokines and their
      receptors, specifically CXCR4 and CCR3, in AD. Immunohistological analysis
      revealed that these chemokine receptors are upregulated in AD patients. Western
      analysis demonstrated an increased activation of PKC, a downstream mediator of
      chemokine receptor signaling, in the majority of AD patients. A very specific
      cohort of genes related to amyloid beta accumulation and clearance were found to
      be significantly altered in AD. The most significantly downregulated gene in this
      data set was the endothelin converting enzyme 2 (ECE2), implicated in amyloid
      beta clearance. These data were subsequently confirmed by real-time PCR and
      Western blot analysis. Together, these findings open up new avenues of
      investigation and possible therapeutic strategies targeting inflammation and
      amyloid clearance in AD patients.

PMID- 17188681
TI  - RBMX is a novel hepatic transcriptional regulator of SREBP-1c gene response to
      high-fructose diet.
AB  - In rodents a high-fructose diet induces metabolic derangements similar to those
      in metabolic syndrome. Previously we suggested that in mouse liver an
      unidentified nuclear protein binding to the sterol regulatory element (SRE)
      binding protein-1c (SREBP-1c) promoter region plays a key role for the response
      to high-fructose diet. Here, using MALDI-TOF MASS technique, we identified an X
      chromosome-linked RNA binding motif protein (RBMX) as a new candidate molecule.
      In electrophoretic mobility shift assay, anti-RBMX antibody displaced the bands
      induced by fructose-feeding. Overexpression or suppression of RBMX on rat
      hepatoma cells regulated the SREBP-1c promoter activity. RBMX may control SREBP
      1c expression in mouse liver in response to high-fructose diet.

PMID- 17188680
TI  - Characterization of glycosomal RING finger proteins of trypanosomatids.
AB  - The glycosomes of trypanosomatids are essential organelles that are
      evolutionarily related to peroxisomes of other eukaryotes. The peroxisomal RING
      proteins-PEX2, PEX10 and PEX12-comprise a network of integral membrane proteins
      that function in the matrix protein import cycle. Here, we describe PEX10 and
      PEX12 in Trypanosoma brucei, Leishmania major, and Trypanosoma cruzi. We
      expressed GFP fusions of each T. brucei coding region in procyclic form T.
      brucei, where they localized to glycosomes and behaved as integral membrane
      proteins. Despite the weak transmembrane predictions for TbPEX12, protease
      protection assays demonstrated that both the N and C termini are cytosolic,
      similar to mammalian PEX12. GFP fusions of T. cruzi PEX10 and L. major PEX12 also
      localized to glycosomes in T. brucei indicating that glycosomal membrane protein
      targeting is conserved across trypanosomatids.

PMID- 17188682
TI  - Fibroblast growth factor-10 prevents H2O2-induced cell cycle arrest by regulation
      of G1 cyclins and cyclin dependent kinases.
AB  - We studied the effects of fibroblast growth factor (FGF-10) on H2O2-induced
      alveolar epithelial cell (AEC) G1 arrest and the role of G1 cyclins. FGF-10
      prevented H2O2-induced AEC G1 arrest. FGF-10 induced 2-4-fold increase in cyclin
      E, cyclin A and CDKs (2,4) alone and in AEC treated with H2O2. H2O2 downregulated
      cyclin D1; FGF-10 blocked these effects. FGF-10 prevented H2O2-induced
      upregulation of CDK inhibitor, p21. SiRNAp21 blocked H2O2-induced downregulation
      of cyclins, CDKs and AEC G1 arrest. Accordingly, we provide first evidence that
      FGF-10 regulates G1 cyclins and CDKs, and prevents H2O2-induced AEC G1 arrest.

PMID- 17188684
TI  - The twin-arginine translocation pathway is necessary for correct membrane
      insertion of the Rieske Fe/S protein in Legionella pneumophila.
AB  - The twin-arginine translocation (Tat) pathway translocates folded proteins across
      the cytoplasmic membrane. Proteins transported through this secretion system
      typically carry two arginine residues in their signal peptide that is cleaved off
      during translocation. Recently, we demonstrated the presence of the Tat pathway
      in Legionella pneumophila Philadelphia-1 and the Rieske Fe/S protein PetA was one
      of the predicted Tat substrates. Because we observed that the signal peptide of
      PetA is not processed and that this protein is still membrane associated in the
      tat mutants, correct membrane insertion was assayed using a trypsin sensitivity
      assay. We conclude that the Tat pathway is necessary for correct membrane
      insertion of L. pneumophila PetA.

PMID- 17188685
TI  - Noise-reduction filtering for accurate detection of replication termini in
      bacterial genomes.
AB  - Bacterial chromosomes are highly polarized in their nucleotide composition
      through mutational selection related to replication. Using compositional skews
      such as the GC skew, replication origin and terminus can be predicted in silico
      by observing the shift points. However, the genome sequence is affected by myriad
      functional requirements and selection on numerous subgenomic features, and
      elimination of this "noise" should lead to better predictions. Here, we present a
      noise-reduction approach that uses low-pass filtering through Fast Fourier
      transform coupled with cumulative skew graphs. It increases the prediction
      accuracy of the replication termini compared with previously documented methods
      based on genomic base composition.

PMID- 17188683
TI  - Phosphorylation by SR kinases regulates the binding of PTB-associated splicing
      factor (PSF) to the pre-mRNA polypyrimidine tract.
AB  - PSF (PTB-associated splicing factor) is a multi-functional protein that
      participates in transcription and RNA processing. While phosphorylation of PSF
      has been shown to be important for some functions, the sites and the kinases
      involved are not well understood. Although PSF does not contain a typical RS
      domain, we report here that PSF is phosphorylated in vivo to generate an
      epitope(s) that can be recognized by a monoclonal antibody specific for
      phosphorylated RS motifs within SR proteins. PSF can be phosphorylated by human
      and yeast SR kinases in vivo and in vitro at an isolated RS motif within its N
      terminus. A functional consequence of SR phosphorylation of PSF is to inhibit its
      binding to the 3' polypyrimidine tract of pre-mRNA. These results indicate that
      PSF is a substrate of SR kinases whose phosphorylation regulates its RNA binding
      capacity and ultimate biological function.

PMID- 17188688
TI  - Stress-induced facilitation of the cortisol response in 17alpha-hydroxylase
      deficient XX mas-1/mas-1 carp (Cyprinus carpio).
AB  - Facilitation of the stress response results from a reduction of the inhibitory
      effects of circulating corticosteroids, allowing an animal to respond to a novel
      stressor. In this study, the existence of a facilitated cortisol stress response
      in normal (STD) and 17alpha-hydroxylase deficient XX mas-1/mas-1 (E5) carp was
      investigated. E5 carp had previously been characterized as having a low cortisol
      response to stress. Fish were subjected to either cortisol feeding or daily-acute
      stress, from 45 until 140 days post-hatch (dph) and were then subjected to a
      novel net-confinement stressor at 141 dph. Growth of E5 fish was reduced in both
      the daily-acute stress and cortisol-fed groups, but STD fish were only affected
      by daily-acute stress. Cortisol feeding had no effect on the stress response of
      STD fish but daily-acute stress significantly inhibited the response to a
      subsequent novel stressor. In contrast, daily-acute stress facilitated the
      cortisol stress response of E5 fish to a novel stressor, while cortisol feeding
      inhibited the cortisol response. Facilitation was accompanied by significant
      enlargement of the head-kidney tissue (which contains the steroidogenic
      interrenal tissue) in E5 fish. To our knowledge this is the first report of
      stress-induced facilitation in a lower vertebrate.

PMID- 17188687
TI  - In situ localization of plethodontid courtship pheromone mRNA in formalin-fixed
      tissue.
AB  - Male plethodontid salamanders produce courtship pheromones that increase female
      receptivity. Three protein components of the courtship pheromone cocktail have
      been characterized in the mental gland of Plethodon shermani, the red-legged
      salamander: plethodontid receptivity factor (PRF), plethodontid modulating factor
      (PMF), and sodefrin precursor-like factor (SPF). In this study, a streamlined in
      situ hybridization (ISH) protocol, employing a biotinylated oligonucleotide
      probe, is used to visualize the sites of pheromone expression in formalin-fixed
      paraffin-embedded P. shermani mental gland and post-cloacal tail tissue. Results
      corroborate previous RT-PCR studies on pheromone expression. PRF and PMF are
      highly expressed in P. shermani mental gland, while SPF expression is more
      variable. None of the tested pheromones is expressed in dorsal or ventral tail
      glands. The reported protocol is simple, rapid, and effective, allowing
      visualization of high-copy mRNA transcript in formalin-fixed tissue.

PMID- 17188686
TI  - Sequestosome 1/p62--more than just a scaffold.
AB  - The interaction of proteins with ubiquitin receptors is key to solving the
      mystery that surrounds the functional role ubiquitin chains play in directing
      traffic. The specificity of these interactions is largely mediated by UbL/UBA
      domains. Sequestosome 1/p62 is a protein that is gaining attention as it is
      intimately involved in cell signaling, receptor internalization, and protein
      turnover. Herein we review recent advances in the field.

PMID- 17188689
TI  - Involvement of the corticotropin-releasing factor (CRF) type 2 receptor in CRF
      induced thyrotropin release by the amphibian pituitary gland.
AB  - Corticotropin-releasing factor (CRF) is considered to be a main
      adrenocorticotropin-releasing factor in vertebrates. In non-mammalian species,
      CRF and related peptides cause the release of thyroid-stimulating hormone (TSH)
      from the anterior pituitary. The actions of CRF peptides are mediated by two G
      protein coupled receptors (CRF1 and CRF2) that have different ligand
      specificities. Using ligands that bind preferentially or selectively to the CRF2
      we tested the hypothesis that TSH release by the amphibian pituitary gland is
      mediated by the CRF2. Injection of frog CRF, urocortin 1 or the CRF2-specific
      ligand urocortin 3 all produced significant, acute increases (by 2 h) in plasma
      thyroxine concentration in prometamorphic tadpoles. Chronic injections of CRF
      peptides accelerated tadpole metamorphosis, and the peptides with the highest
      affinity for the CRF2 (urocortin 1 and sauvagine) had the greatest potency.
      Ligands selective for the CRF2 (frog urocortin 3, mouse urocortins 2 and 3) all
      accelerated tadpole metamorphosis. We then tested frog urocortins 1 and 3, mouse
      urocortin 2 and sauvagine for their TSH-releasing activity using dispersed frog
      anterior pituitary cells in culture. All of the peptides tested markedly enhanced
      the release of TSH. Secretagogue-induced TSH release was completely blocked by
      the general CRF receptor antagonist astressin or the CRF2-specific antagonist
      antisauvagine-30. Conversely, the type 1 CRF receptor-specific antagonist
      antalarmin had no effect on TSH secretion. Our results support the hypothesis
      that CRF-induced TSH release by the amphibian pituitary gland is mediated by the
      CRF2.

PMID- 17188690
TI  - Parathyroid hormone-related protein in teleost fish.
AB  - A brief description is given of the discovery of PTHrP and the roles of the
      peptide in mammalian physiology. Next, the occurrence of PTHrP in the earliest
      vertebrates, sharks, skates and fishes, is reviewed and the calciotropic
      functions of PTHrP are addressed more specifically in fishes. Parathyroid hormone
      related protein (PTHrP) is a hypercalcemic hormone in teleostean fishes, but also
      has para- and autocrine functions. After the isolation and identification of fish
      PTHrP and PTHrP receptors and the subsequent development of recombinant protein
      and a real-time quantitative PCR, a calciotropic role of PTHrP in fish physiology
      could be assessed. PTHrP influences calcium physiology via regulation of calcium
      mobilisation from internal sources (bone and scales) and via calcium uptake from
      the environment (water and diet). Continuous variations in the need for calcium
      and in the availability of environmental calcium require fast calciotropes to
      guarantee calcium balance, in which PTHrP is pivotal for the fish. PTHrP is
      essential in fish bone physiology, e.g. in mineralisation and calcium
      reabsorption from the scales. Moreover, PTHrP plays a role in vitellogenesis,
      cortisol production, regulation of renal Mrp2 activity and melatonin synthesis.
      The plethora of functions of PTHrP in fish concern endocrine, paracrine and
      autocrine (and possibly intracrine) functions; calciotropic actions of PTHrP at
      the organismal and cellular level are prominent in fish. The strong conservation
      of the pthrp gene in the vertebrate lineage and the N-terminal similarity of the
      coded proteins relates to the important role of PTHrP in calcium physiology that
      is of paramount importance to all physiological processes. Recent and ongoing
      studies will contribute to our rapidly expanding knowledge of the original
      physiological functions of PTHrP in teleost fish.

PMID- 17188691
TI  - Vaginal misoprostol for salvage therapy after failed medical abortion.

PMID- 17188692
TI  - Breakfast as a screening test for gestational diabetes.

PMID- 17188693
TI  - Derivatisation using m-(trifluoromethyl)phenyltrimethylammonium hydroxide of
      organic materials in artworks for analysis by gas chromatography-mass
      spectrometry: unusual reaction products with alcohols.
AB  - The quaternary ammonium reagent m-(trifluoromethyl)phenyltrimethylammonium
      hydroxide (TMTFTH) has gained widespread use for the derivatisation for GCMS
      analysis of organic materials found in artists' materials, such as oils, plant
      resins and waxes. This paper discusses products formed from reactions of TMTFTH
      with alcohols--including fatty alcohols, hydroxyacids, terpenes and glycerol-
      that have diagnostic value in the analysis of samples from artworks. In addition
      to methyl ethers, (trifluoromethyl)phenyl ethers were formed to variable degrees
      from the different types of alcohol. The products were identified from their EI
      mass spectra. An understanding of these multiple reaction products is important
      for the interpretation of GCMS data from complex samples, especially in the case
      of polyfunctional alcohols such as glycerol, which forms a number of methyl,
      (trifluoromethyl)phenyl and mixed ethers. The significance of the reaction
      products, and the relative advantages of TMTFTH as compared to alternative
      ammonium and sulfonium methylating reagents, are discussed.

PMID- 17188694
TI  - Optimization of simulated moving bed and column chromatography for a plasmid DNA
      purification step and for a chiral separation.
AB  - This work analyzes the performance of the SMB and the column chromatography
      processes for two different case studies: the first stage of the plasmid DNA
      (pDNA) polishing, and the Troger's base enantiomer separation, in which the
      adsorption isotherms are linear and non-linear, respectively. Simulation tools
      are used together with an optimization routine (Non-Sorting Genetic Algorithm
      (NSGA)) in order to find the optimum operating conditions leading to maximum
      productivity and minimum solvent consumption; the optimum solution for each of
      the processes is a curve on the productivity-solvent consumption plane, the so
      called Pareto set. The comparison between the column and the SMB processes is
      based on the relative position of the two Pareto sets calculated at equal
      conditions and for the same final purity and recovery of the target species. The
      results show that SMB is superior to column chromatography in the two case
      studies investigated, i.e. in the case of the linear isotherm (pDNA), the
      productivity gain is up to a factor two for a given value of the solvent
      consumption. Furthermore, the flexibility of the SMB operation is larger, since
      the Pareto sets are flatter and they prolong into regions of the productivity
      solvent consumption plane that are not accessible with the column chromatography
      process.

PMID- 17188695
TI  - Solvation parameter models for retention on perfluorinated and fluorinated low
      temperature glassy carbon stationary phases in reversed-phase liquid
      chromatography.
AB  - The retention of solutes on two fluorinated low temperature glassy carbon (F
      LTGC) stationary phases under reversed-phase liquid chromatographic conditions
      was studied by employing the solvation parameter model. The two fluorinated
      glassy carbon stationary phases were produced by slowly heating zirconia
      particles that were encapsulated with oligo[1,3-dibutadiyne-1,3
      (tetrafluoro)phenylene] precursor polymer to two different final temperatures
      (200 and 400 degrees C). The resulting carbon particles had different amounts of
      fluorine after thermal processing. The solvation parameter models indicated that
      different intermolecular interactions are important in describing retention on
      the two stationary phases. The interactions that are important for describing
      retention on the 200 degrees C processed F-LTGC stationary phase are hydrogen
      bond basicity> or =dispersion>hydrogen bond acidity>dipolarity/polarizability.
      The interactions that describe the retention on the 400 degrees C processed F
      LTGC are hydrogen bond basicity>dispersion>excess molar refraction> or =hydrogen
      bond acidity. The solvation parameter model for the 200 degrees C processed F
      LTGC showed similar trends in the relative importance of intermolecular
      interactions as previously found for octadecyl-polysiloxane stationary phases,
      while the 400 degrees C processed F-LTGC had similar intermolecular interactions
      with solutes as found with porous glassy carbon in that pi-pi interactions with
      the carbon surface contribute more so to the retention.

PMID- 17188696
TI  - In-tube solid-phase microextraction-capillary liquid chromatography as a solution
      for the screening analysis of organophosphorus pesticides in untreated
      environmental water samples.
AB  - This paper describes a method for the selective screening of organophosphorus
      pesticides in water. In-tube solid-phase microextraction (SPME) in an open
      capillary column coupled to capillary liquid chromatography (LC) with UV
      detection has been used to effect preconcentration, separation and detection of
      the analytes in the same assembly. For in-tube SPME two capillary columns of the
      same length and different internal diameters and coating thicknesses have been
      tested and compared, a 30 cm x 0.25 mm I.D., 0.25 micro m thickness coating
      column, and a 30 cm x 0.1 mm I.D., 0.1 micro m of coating thickness column. In
      both columns the coating was 95% dimethylpolysiloxane (PDMS)-5%
      diphenylpolysiloxane. The proposed methodology provided limits of detections
      (LODs) for the tested organophosphorus pesticides in the 0.1-10 micro g/L range,
      whereas the direct injection of the samples onto the capillary LC system provided
      LODs in the 50-1000 micro g/L range. The sensitivity of the proposed in-tube SPME
      capillary LC method is adequate to monitorize the analyte levels in drinking
      water. Several triazines, polycyclic aromatic hydrocarbons (PAHs), nonylphenol,
      organochloride pesticides or polybrominated diphenyl ethers (PBDEs) have been
      evaluated as possible interferents. The reliability of the described method is
      demonstrated by analysing different real water samples.

PMID- 17188697
TI  - Selective sampling of multiply phosphorylated peptides by capillary
      electrophoresis for electrospray ionization mass spectrometry analysis.
AB  - The ionization of phosphorylated peptides in positive ion mode mass spectrometry
      is generally less efficient compared with the ionization of their non
      phosphorylated counterparts. This can make phosphopeptides much more difficult to
      detect. One way to enhance the detection of phosphorylated proteins and peptides
      is by selectively isolating these species. Current approaches of phosphopeptide
      isolation are based on the favorable interactions of phosphate groups with
      immobilized metals. While these methods can be effective in the extraction, they
      can lead to incomplete sample recovery, particularly for the most strongly bound
      multiply phosphorylated components. A non-sorptive method of phosphopeptide
      isolation using capillary electrophoresis (CE) was recently reported [Zhang et
      al., Anal. Chem. 77 (2005) 6078]. The relatively low isoelectric points of
      phosphopeptides cause them to remain anionic at acidic sample pH. Hence, they can
      be selectively injected into the capillary by an applied field after the
      electroosmotic flow (EOF) is suppressed. The technique was previously coupled
      with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). In
      this work, the exploitation of selective sampling in conjugation with
      electrospray ionization mass spectrometry (ESI-MS) is presented. The transition
      was not immediately straightforward. A number of major alterations were necessary
      for ESI interfacing. These adaptations include the choice of a suitable capillary
      coating for EOF control and the incorporation of organic solvent for efficient
      ESI. As expected, selective injection of phosphopeptides greatly enhanced the
      sensitivity of their detection in ESI-MS, particularly for the multiply
      phosphorylated species that were traditionally most problematic. Furthermore, an
      electrophoretic separation subsequent to the selective injection of the
      phosphopeptides was performed prior to analysis by ESI-MS. This allowed us to
      resolve the multiply phosphorylated peptides present in the samples,
      predominantly based on the number of phosphorylation sites on the peptides.

PMID- 17188698
TI  - Preparation of high efficiency and highly retentive monolithic silica capillary
      columns for reversed-phase chromatography by chemical modification by
      polymerization of octadecyl methacrylate.
AB  - High efficiency and highly retentive monolithic silica capillary columns were
      obtained by polymerization of octadecyl methacrylate using alpha,alpha'-azobis
      isobutyronitrile (AIBN) as a free radical initiator. Hybrid type monolithic
      silica columns (25 cm total length x 200 microm I.D.) prepared from a mixture of
      tetramethoxysilane and methyltrimethoxysilane were used as a support. The effects
      of the monomer and the radical initiator concentrations in the reaction mixture
      were examined. The performance of the columns was tested in terms of column
      efficiency and retention behavior by using alkylbenzenes and a few other
      compounds as solutes and compared with that of hybrid monolithic silica columns
      modified with octadecylsilyl-(N,N-diethylamino)silane (ODS-DEA). Highly retentive
      monolithic silica columns were obtained by polymerization at high monomer
      concentrations. Although a decrease in column efficiency was observed with the
      increase in the monomer concentration in a feed mixture, an improvement in
      efficiency was achieved (a plate height value lower than 10 microm) by increasing
      an initiator concentration without significant variations in column retention
      properties. Results obtained by polymerization using other monomers are also
      presented to demonstrate the applicability of the preparation method.

PMID- 17188699
TI  - Identification of yeast oxidized proteins: chromatographic top-down approach for
      identification of carbonylated, fragmented and cross-linked proteins in yeast.
AB  - The effects of oxidative stress on the yeast proteome were studied using hydrogen
      peroxide as the stress agent. Oxidized proteins were isolated by (1)
      biotinylation of oxidized proteins with biotin hydrazide, (2) affinity selection
      using monomeric avidin affinity chromatography, and (3) further fractionated by
      reversed-phase liquid chromatography (RPLC) on a C(8) column. Oxidized protein
      fractions from RPLC were then trypsin digested and the peptide cleavage fragments
      identified by tandem mass spectrometry (MS/MS). Slightly over 400 proteins were
      identified. Sites of carbonyl formation were found in roughly one fourth of these
      proteins. Oxidation on other amino acids in carbonylated peptides was seen in 32
      cases while carbonylation was absent in 96 of the oxidized proteins observed.
      Although there are large numbers of potential oxidation sites, oxidation seemed
      to be restricted to a small area in most of the proteins identified. Sometimes
      multiple amino acids in the same tryptic peptide were oxidized. A second trend
      was that more than 8% of the proteins identified appeared in more than one of the
      RPLC fractions. Based on the position of the peptides identified in the primary
      structure of protein candidates derived from databases it was concluded that this
      occurred by fragmentation of a parent protein. It is not clear from the data
      whether the fragmentation process was of enzymatic or oxidative origin. Finally,
      peptides from two or more proteins occurred together in more than one reversed
      phase fraction with 2% of the proteins identified. This data was interpreted to
      mean that this was the result of protein cross-linking.

PMID- 17188700
TI  - Vanguard/rearguard strategy for the evaluation of the degradation of yoghurt
      samples based on the direct analysis of the volatiles profile through headspace
      gas chromatography-mass spectrometry.
AB  - A vanguard/rearguard analytical strategy for the monitoring of the degradation of
      yoghurt samples is proposed. The method is based on the headspace-gas
      chromatography-mass spectrometry (HS-GC-MS) instrumental coupling. In this
      combination, the chromatographic column is firstly used as an interface between
      the HS and the MS (vanguard mode) avoiding separation of the volatile components
      by maintaining the chromatographic oven at high, constant temperature. By
      changing the thermal conditions of the oven, the aldehydes can be properly
      separated for individual identification/quantification (rearguard mode). In the
      vanguard method, the quantification of the volatile aldehydes was calculated
      through partial least square and given as a total index. The rearguard method
      permits the detection of the aldehydes at concentrations between 12 and 35 ng/g.
      Both methods were applied to the study of the environmental factors favouring the
      presence of the volatile aldehydes (C(5)-C(9)) in the yoghurt samples. Principal
      component analysis of the total concentration of aldehydes with the time (from 0
      to 30 days) demonstrates the capability of the HS-MS coupling for the estimation
      of the quality losses of the samples. The results were corroborated by the HS-GC
      MS which also indicates that pentanal was present in the yoghurt from the
      beginning of the study and the combination of light/oxygen was the most negative
      influence for sample conservation.

PMID- 17188701
TI  - Adsorbed para-nitrophenol on HDTMAB organoclay--a TEM and infrared spectroscopic
      study.
AB  - para-Nitrophenol adsorbed on hexadecyltrimethylammonium bromide modified
      montmorillonite has been studied using a combination of X-ray diffraction TEM and
      infrared spectroscopy. Upon formation of the organoclay, the properties change
      from hydrophilic to hydrophobic. It is proposed that para-nitrophenol is adsorbed
      onto the water in the cation hydration sphere of the organoclay. As the cation is
      replaced by the surfactant molecules the para-nitrophenol replaces the surfactant
      molecules in the clay interlayer. Significant changes in the water vibrations
      occur in this process. Bands attributed to CH stretching and bending vibrations
      in general decrease as the concentration of the surfactant (CEC) increases up to
      1.0 CEC. After this concentration the bands increase approaching a value the same
      as that of the surfactant. Strong changes occur in the HCH deformation modes of
      the methyl groups of the surfactant. These changes are attributed to the methyl
      groups locking into the siloxane surface of the montmorillonite. Such a concept
      is supported by changes in the SiO stretching bands of the montmorillonite
      siloxane surface. This study demonstrates that para-nitrophenol will penetrate
      into the untreated clay interlayer and replace the intercalated surfactant in
      surfactant modified clay, resulting in the change of the arrangement of the
      intercalated surfactant.

PMID- 17188702
TI  - Ultrasonic velocity measurements as a method for investigating phase transitions
      of monoglyceride emulsifier systems in pearlescent cosmetic creams.
AB  - The phase transitions of monoglyceride emulsifier systems and pearlescent effects
      in cosmetic creams are investigated using ultrasonic velocity measurements. The
      transitions between the different phases of monoglyceride emulsifier systems--the
      coagel, liquid-crystalline lamellar phase, and gel phase--are detected in creams
      by changes in the ultrasonic velocity with variation of the temperature. The
      phase transition temperatures correspond to DSC results. Furthermore, the slope
      of the ultrasound velocity curve correlates with the amount of bound water in the
      different phases. These insights into the ultrasonic velocity properties of the
      monoglyceride emulsifier system of creams make it possible to more closely study
      the pearlescent effect of the coagel. The temperature domain of the short time
      reversibility of the pearlescence as well as the back-formation time of the
      coagel can be determined with this method, which enable the optimization of the
      formulation of pearlescent creams.

PMID- 17188703
TI  - Preparation and structural evolution of SiO(2)-TiO(2) pillared layered manganese
      oxide nanocomposite upon intercalating reaction.
AB  - SiO(2)-TiO(2) pillared layered manganese oxide nanohybrid was successfully
      synthesized by preliminarily expanding the interlayer of H-type layered manganese
      oxide using dodecylamine, followed by reacting it with a mixture solution of
      titanium isopropoxide and tetraethylorthosilicate. The basal spacing and the
      pillared agent content of the obtained materials connected with the length of
      intercalated n-alkylamine, incorporated Si/Ti molar ratios and the solvothermal
      treatment temperature. The structural evolution of SiO(2)-TiO(2) pillared layered
      manganese oxide nanohybrid was characterized by XRD, DSC-TGA, SEM, IR, N(2)
      adsorption-desorption and element analyses. TiO(2) particles exhibited a stronger
      affinity for the negatively charged manganese layers, and the TiO(2) particles
      incorporated were independently intercalated without any distinct chemical
      bonding with the co-intercalated SiO(2) particles. SiO(2)-TiO(2) pillared layered
      manganese oxide nanohybrid had a BET surface area of 98 m(2)/g with a gallery
      height of about 1.43 nm between layers. The obtained SiO(2)-TiO(2) co-pillared
      layered manganese oxide nanohybrid is expected as a selective catalyst, or an
      improved battery material.

PMID- 17188704
TI  - Cytokine-neuroantigen fusion proteins: new tools for modulation of myelin basic
      protein (MBP)-specific T cell responses in experimental autoimmune
      encephalomyelitis.
AB  - Fusion proteins incorporating anti-inflammatory cytokines and immunodominant self
      antigen as separate domains of a single protein may hold promise for development
      of antigen-specific tolerogenic vaccines. Proteins incorporating rat sequences of
      IL-1RA, IL-2, IL-4, IL-10, or IL-13 were expressed as fusion proteins containing
      the major encephalitogenic region of myelin basic protein (MBP). These fusion
      proteins were expressed via baculovirus (bv) expression systems and were shown to
      have cytokine-dependent and antigen-specific biological activity. In the case of
      the IL-2 and IL-4 fusion proteins, covalent linkage of the cytokine and
      neuroantigen domains resulted in synergistic antigen presentation. These data
      indicate that the cytokine domain may be able to modulate APC activity and
      simultaneously target the covalently tethered NAg for enhanced presentation by
      certain APC subsets. Cytokine/antigen fusion proteins may represent a novel tool
      for antigen-specific immune modulation in autoimmune disease.

PMID- 17188705
TI  - Evaluation of human mast cell-mediated cytotoxicity by DIOC18 target cell
      labeling in flow cytometry.
AB  - (51)Cr release assay (CRA) is still the standard method to study mast cell (MC)
      mediated cytotoxicity in vitro. Non-radioactive methods e.g. MTT, Hoechst 22147
      staining, have also been used. Though CRA has the benefit of being reproducible,
      it has several drawbacks e.g. spontaneous release and radioactivity. The basic
      strategy of this new flow cytometric assay involves labeling target cells with
      DIOC18, in addition to staining with propidium iodide to identify dead cells. 8
      week-old human MCs were used as effectors. Human LAK-sensitive K-562; and LAK
      resistant myeloid leukemia cell lines (DAMI, HL-60 and Meg-01) as well as 6 LAK
      resistant myeloid leukemia patient samples were utilized. MCs/targets were co
      incubated in certain ratios for short/long-term. Although there was some
      insignificant killing at 2 h/18 h, probably due to small sample size, significant
      killing in Meg-01 and HL-60 cells (27% and 39%; respectively) was observed at 48
      h. This method clearly showed human MC-mediated cytotoxicity against human tumor
      cells. It was reproducible, reliable and cheaper without any radiation and
      spontaneous release. This is the first study to elucidate MC-mediated
      cytotoxicity by a flow cytometric assay.

PMID- 17188706
TI  - Activation of proMMP-2 and Src by HHV8 vGPCR in human pulmonary arterial
      endothelial cells.
AB  - Idiopathic pulmonary arterial hypertension (iPAH) is associated with human
      herpesvirus 8 (HHV8) infection and demonstrates pathological angiogenesis similar
      to that observed with another HHV8-linked disease, namely Kaposi Sarcoma (KS).
      Importantly, the HHV8 encoded viral G-protein-coupled receptor (vGPCR) induces KS
      lesions in a murine model. Investigating the impact of vGPCR expression on the
      angiogenic activity of human pulmonary arterial endothelial cells (HPAEC) can
      yield insight into the pathobiology of HHV8-associated vascular disorders,
      particularly PAH. Cultured HPAECs were transduced with retroviral vectors
      carrying either control or vGPCR coding regions. vGPCR expression selectively
      activated matrix metalloproteinase (MMP)-2, a pivotal matrix modulating enzyme
      during angiogenesis. A membrane type 1 MMP (MT1-MMP) neutralizing antibody and
      the tissue inhibitor of metalloproteinases-2 (TIMP-2) independently blocked vGPCR
      induced MMP-2 activation. vGPCR expression concordantly promoted MMP-2 activation
      by increasing MT1-MMP expression while decreasing TIMP-2 expression. vGPCR
      activated Src kinase as demonstrated by phosphorylation of Src and its substrate
      focal adhesion kinase (FAK). vGPCR promoted angiogenesis of HPAECs as
      demonstrated by a substantial increase in tubulogenesis in vitro. The Src
      inhibitors PP2 and SU6656 significantly diminished vGPCR-induced MMP-2 activation
      and tubulogenesis. Our findings indicate that vGPCR induces MMP-2 activation in
      HPAECs through regulation of MT1-MMP and TIMP-2 expression. vGPCR activates Src
      and inhibition of such activation abrogates proMMP-2 activation and in vitro
      angiogenesis induced by vGCPR. The current study implicates vGPCR as an
      etiological agent in iPAH and identifies Src and MMP-2 as potential therapeutic
      targets in HHV8 associated KS and iPAH.

PMID- 17188707
TI  - AMPK control of myocardial fatty acid metabolism fluctuates with the intensity of
      insulin-deficient diabetes.
AB  - Flexibility in substrate selection is essential for the heart to maintain
      production of energy and contractile function, and is managed through multiple
      mechanisms including PPAR-alpha and AMP-activated protein kinase (AMPK). Rats
      injected with 55 mg/kg STZ (D55) were kept for 4 days (acute diabetes; D55-A)
      prior to termination. Fatty acid (FA) oxidation increased in D55-A hearts, with
      no significant change in gene expression of PPAR-alpha, or its downstream
      targets. However, both AMPK and ACC phosphorylation were significantly higher in
      these hearts, effects that were reversed by insulin. Unexpectedly, when the
      duration of diabetes in D55 rats was extended to 6 weeks (chronic diabetes; D55
      C), AMPK and ACC phosphorylation were comparable in control and D55-C hearts. In
      D55-C rat hearts, lack of AMPK activation was closely associated to an overload
      of plasma and cardiac lipids. To validate the relationship between lipids and
      cardiac AMPK activation, we either induced more severe diabetes (100 mg/kg STZ to
      provoke both hyperglycemia and hyperlipidemia acutely; D100-A) or infused
      intralipid (IL) to enlarge circulating lipids. There was no difference in cardiac
      AMPK and ACC phosphorylation in D100-A rats compared to control. Measurement of
      AMPK and ACC phosphorylation in control and D55-A hearts revealed that their
      phosphorylation was inhibited by acute intralipid infusion. Our data suggest that
      activation of AMPK is an adaptation that would ensure adequate cardiac energy
      production when glucose utilization is compromised. However, in severe diabetes,
      with the addition of augmented plasma and heart lipids, AMPK activation is
      prevented, and control of FA oxidation is likely through alternate mechanisms.
      Given that AMPK plays an important role in preventing cardiac
      ischemic/reperfusion damage, it is possible that in these diabetic hearts, the
      accelerated damage observed during exposure to ischemia/reperfusion could be a
      likely outcome of a compromised activation of AMPK.

PMID- 17188709
TI  - Role of the charge-charge interactions in defining stability and halophilicity of
      the CspB proteins.
AB  - Charge-charge interactions on the surface of native proteins are important for
      protein stability and can be computationally redesigned in a rational way to
      modulate protein stability. Such computational effort led to an engineered
      protein, CspB-TB that has the same core as the mesophilic cold shock protein CspB
      Bs from Bacillus subtilis, but optimized distribution of charge-charge
      interactions on the surface. The CspB-TB protein shows an increase in the
      transition temperature by 20 degrees C relative to the unfolding temperature of
      CspB-Bs. The CspB-TB and CspB-Bs protein pair offers a unique opportunity to
      further explore the energetics of charge-charge interactions as the substitutions
      at the same sequence positions are done in largely similar structural but
      different electrostatic environments. In particular we addressed two questions.
      What is the contribution of charge-charge interactions in the unfolded state to
      the protein stability and how amino acid substitutions modulate the effect of
      increase in ionic strength on protein stability (i.e. protein halophilicity). To
      this end, we experimentally measured the stabilities of over 100 variants of CspB
      TB and CspB-Bs proteins with substitutions at charged residues. We also performed
      computational modeling of these protein variants. Analysis of the experimental
      and computational data allowed us to conclude that the charge-charge interactions
      in the unfolded state of two model proteins CspB-Bs and CspB-TB are not very
      significant and computational models that are based only on the native state
      structure can adequately, i.e. qualitatively (stabilizing versus destabilizing)
      and semi-quantitatively (relative rank order), predict the effects of surface
      charge neutralization or reversal on protein stability. We also show that the
      effect of ionic strength on protein stability (protein halophilicity) appears to
      be mainly due to the screening of the long-range charge-charge interactions.

PMID- 17188708
TI  - Statin and resveratrol in combination induces cardioprotection against myocardial
      infarction in hypercholesterolemic rat.
AB  - Hypercholesterolemia (HC) is a common health problem that significantly increases
      risk of cardiovascular disease. Both statin (S) and resveratrol (R) demonstrated
      cardioprotection through nitric oxide-dependent mechanism. Therefore, the present
      study was undertaken to determine whether combination therapy with statin and
      resveratrol is more cardioprotective than individual treatment groups in ischemic
      rat heart model. The rats were fed with 2% high cholesterol diet and after 8
      weeks of high cholesterol diet the animals were treated with statin (1 mg/kg
      bw/day) and resveratrol (20 mg/kg bw/day) for 2 weeks. The rats were assigned to:
      (1) Control (C), (2) HC, (3) HCR, (4) HCS and (5) HCRS. The hearts, subjected to
      30-min global ischemia followed by 120-min reperfusion were used as experimental
      model. The left ventricular functional recovery (+dp/dt(max)) was found to be
      significantly better in the HCRS (1926+/-43), HCR (1556+/-65) and HCS (1635+/-40)
      compared to HC group (1127+/-16). The infarct sizes in the HCRS, HCS and HCR
      groups were 37+/-3.6, 43+/-3.3 and 44+/-4.2 respectively compared to 53+/-4.6 in
      HC. The lipid level was found to be decreased in all the treatment groups when
      compared to HC more significantly in HCS and HCRS groups when compared to HCR.
      Increased phosphorylation of Akt and eNOS was also observed in all the treatment
      groups resulting in decreased extent of cardiomyocyte apoptosis but the extent of
      reduction in apoptosis was more significant in HCRS group compared to all other
      groups. In vivo rat myocardial infarction (MI) model subjected to 1 week of
      permanent left descending coronary artery (LAD) occlusion documented increased
      capillary density in HCR and HCRS treated group when compared to HCS treatment
      group. We also documented increased beta-catenin translocation and increased VEGF
      mRNA expression in all treatment groups. Thus, we conclude that the acute as well
      as chronic protection afforded by combination treatment with statin and
      resveratrol may be due to pro-angiogenic, anti-hyperlipidemic and anti-apoptotic
      effects and long-term effects may be caused by increased neo-vascularization of
      the MI zone leading to less ventricular remodeling.

PMID- 17188710
TI  - Point mutations in the HIV-1 matrix protein turn off the myristyl switch.
AB  - During the late phase of human immunodeficiency virus type-1 (HIV-1) replication,
      newly synthesized retroviral Gag proteins are targeted to lipid raft regions of
      specific cellular membranes, where they assemble and bud to form new virus
      particles. Gag binds preferentially to the plasma membrane (PM) of most
      hematopoietic cell types, a process mediated by interactions between the cellular
      PM marker phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P(2)) and Gag's N
      terminally myristoylated matrix (MA) domain. We recently demonstrated that
      PI(4,5)P(2) binds to a conserved cleft on MA and promotes myristate exposure,
      suggesting a role as both a direct membrane anchor and myristyl switch trigger.
      Here we show that PI(4,5)P(2) is also capable of binding to MA proteins
      containing point mutations that inhibit membrane binding in vitro, and in vivo,
      including V7R, L8A and L8I. However, these mutants do not exhibit PI(4,5)P(2) or
      concentration-dependent myristate exposure. NMR studies of V7R and L8A MA reveal
      minor structural changes that appear to be responsible for stabilizing the
      myristate-sequestered (myr(s)) species and inhibiting exposure. Unexpectedly, the
      myristyl group of a revertant mutant with normal PM targeting properties
      (V7R,L21K) is also tightly sequestered and insensitive to PI(4,5)P(2) binding.
      This mutant binds PI(4,5)P(2) with twofold higher affinity compared with the
      native protein, suggesting a potential compensatory mechanism for membrane
      binding.

PMID- 17188711
TI  - Exclusion of glucosyl-hydroxymethylcytosine DNA containing bacteriophages is
      overcome by the injected protein inhibitor IPI*.
AB  - The Escherichia coli isolate CT596 excludes infection by the Myoviridae T4 ip1(-)
      phage that lacks the encapsidated IPI* protein normally injected into the host
      with the phage DNA. Screening of a CT596 genomic library identified adjacent
      genes responsible for this exclusion, gmrS (942 bp) and gmrD (708 bp) that are
      encoded by a cryptic prophage DNA. The two genes are necessary and sufficient to
      confer upon a host the ability to exclude infection by T4 ip1(-) phage and other
      glucosyl-hydroxymethylcytosine (glc-HMC) Tevens lacking the ip1 gene, yet allow
      infection by phages with non-glucoslyated cytosine (C) DNA that lack the ip1
      gene. A plasmid expressing the ip1 gene product, IPI*, allows growth of Tevens
      lacking ip1 on E. coli strains carrying the cloned gmrS/gmrD genes. Members of
      the Teven family carry a diverse and, in some cases, expanded set of ip1 locus
      genes. In vivo analysis suggests a family of gmr genes that specifically target
      sugar-HMC modified DNA have evolved to exclude Teven phages, and these exclusion
      genes have in turn been countered by a family of injected exclusion inhibitors
      that likely help determine the host range of different glc-HMC phages.

PMID- 17188712
TI  - NMR analysis of the conformational properties of the trapped on-pathway folding
      intermediate of the bacterial immunity protein Im7.
AB  - Previous work shows that the transiently populated, on-pathway intermediate in
      Im7 folding contains three of the four native alpha-helices docked around a core
      stabilised by native and non-native interactions. To determine the structure and
      dynamic properties of this species in more detail, we have used protein
      engineering to trap the intermediate at equilibrium and analysed the resulting
      proteins using NMR spectroscopy and small angle X-ray scattering. Four variants
      were created. In L53AI54A, two hydrophobic residues within helix III are
      truncated, preventing helix III from docking stably onto the developing
      hydrophobic core. In two other variants, the six residues encompassing the native
      helix III were replaced with three (H3G3) or six (H3G6) glycine residues. In the
      fourth variant, YY, two native tyrosine residues (Tyr55 and Tyr56) were re
      introduced into H3G6 to examine their role in determining the properties of the
      intermediate ensemble. All four variants show variable peak intensities and broad
      peak widths, consistent with these proteins being conformationally dynamic.
      Chemical shift analyses demonstrated that L53AI54A and YY contain native-like
      secondary structure in helices I and IV, while helix II is partly formed and
      helix III is absent. Lack of NOEs and rapid NH exchange for L53AI54A, combined
      with detailed analysis of the backbone dynamics, indicated that the hydrophobic
      core of this variant is not uniquely structured, but fluctuates on the NMR
      timescale. The results demonstrate that though much of the native-like secondary
      structure of Im7 is present in the variants, their hydrophobic cores remain
      relatively fluid. The comparison of H3G3/H3G6 and L53AI54A/YY suggests that Tyr55
      and/or Tyr56 interact with the three-helix core, leading other residues in this
      region of the protein to dock with the core as folding progresses. In this
      respect, the three-helix bundle acts as a template for formation of helix III and
      the creation of the native fold.

PMID- 17188713
TI  - The R269H mutation in presenilin-1 presenting as late-onset autosomal dominant
      Alzheimer's disease.
AB  - Two siblings fulfilling clinical diagnostic criteria for late-onset Alzheimer's
      disease (AD) are reported. The family history suggested a total of nine
      individuals affected with AD in three generations with autosomal dominant disease
      transmission. Neurogenetic testing of the proband revealed a mutation, R269H, in
      the presenilin-1 (PS1) gene. Late-onset AD may be associated with deterministic
      PS1 mutations; these should be sought when the family history suggests autosomal
      dominant disease transmission.

PMID- 17188714
TI  - A stochastic mathematical model of methicillin resistant Staphylococcus aureus
      transmission in an intensive care unit: predicting the impact of interventions.
AB  - OBJECTIVES: To estimate the transmission rate of MRSA in an intensive care unit
      (ICU) in an 800 bed Australian teaching hospital and predict the impact of
      infection control interventions. METHODS: A mathematical model was developed
      which consisted of four compartments: colonised and uncolonised patients and
      contaminated and uncontaminated health-care workers (HCWs). Patient movements,
      MRSA acquisition and daily prevalence data were collected from an ICU over 939
      days. Hand hygiene compliance and the probability of MRSA transmission from
      patient to HCW per discordant contact were measured during the study. Attack rate
      and reproduction ratio were estimated using Bayesian methods. The impact of a
      number of interventions on attack rate was estimated using both stochastic and
      deterministic versions of the model. RESULTS: The mean number of secondary cases
      arising from the ICU admission of colonised patients, also called the ward
      reproduction ratio, R(w), was estimated to be 0.50 (95% CI 0.39-0.62). The attack
      rate was one MRSA transmission per 160 (95% CI 130-210) uncolonised-patient days.
      Results were not sensitive to uncertainty in measured model parameters (hand
      hygiene rate and transmission probability per contact). Hand hygiene was
      predicted to be the most effective intervention. Decolonisation was predicted to
      be relatively ineffective. Increasing HCW numbers was predicted to increase MRSA
      transmission, in the absence of patient cohorting. The predictions of the
      stochastic model differed from those of the deterministic model, with lower
      levels of colonisation predicted by the stochastic model. CONCLUSIONS: The number
      of secondary cases of MRSA colonisation within the ICU in this study was below
      unity. Transmission of MRSA was sustained through admission of colonised
      patients. Stochastic model simulations give more realistic predictions in
      hospital ward settings than deterministic models. Increasing staff does not
      necessarily lead to reduced transmission of nosocomial pathogens.

PMID- 17188715
TI  - Robustness and evolvability in genetic regulatory networks.
AB  - Living organisms are robust to a great variety of genetic changes. Gene
      regulation networks and metabolic pathways self-organize and reaccommodate to
      make the organism perform with stability and reliability under many point
      mutations, gene duplications and gene deletions. At the same time, living
      organisms are evolvable, which means that these kind of genetic perturbations can
      eventually make the organism acquire new functions and adapt to new environments.
      It is still an open problem to determine how robustness and evolvability blend
      together at the genetic level to produce stable organisms that yet can change and
      evolve. Here we address this problem by studying the robustness and evolvability
      of the attractor landscape of genetic regulatory network models under the process
      of gene duplication followed by divergence. We show that an intrinsic property of
      this kind of networks is that, after the divergence of the parent and duplicate
      genes, with a high probability the previous phenotypes, encoded in the attractor
      landscape of the network, are preserved and new ones might appear. The above is
      true in a variety of network topologies and even for the case of extreme
      divergence in which the duplicate gene bears almost no relation with its parent.
      Our results indicate that networks operating close to the so-called "critical
      regime" exhibit the maximum robustness and evolvability simultaneously.

PMID- 17188716
TI  - Modeling human mortality using mixtures of bathtub shaped failure distributions.
AB  - Aging and mortality is usually modeled by the Gompertz-Makeham distribution,
      where the mortality rate accelerates with age in adult humans. The resulting
      parameters are interpreted as the frailty and decrease in vitality with age. This
      fits well to life data from 'westernized' societies, where the data are accurate,
      of high resolution, and show the effects of high quality post-natal care. We
      show, however, that when the data are of lower resolution, and contain
      considerable structure in the infant mortality, the fit can be poor. Moreover,
      the Gompertz-Makeham distribution is consistent with neither the force of natural
      selection, nor the recently identified 'late life mortality deceleration'.
      Although actuarial models such as the Heligman-Pollard distribution can, in
      theory, achieve an improved fit, the lack of a closed form for the survival
      function makes fitting extremely arduous, and the biological interpretation can
      be lacking. We show, that a mixture, assigning mortality to exogenous or
      endogenous causes, using the reduced additive and flexible Weibull distributions,
      models well human mortality over the entire life span. The components of the
      mixture are asymptotically consistent with the reliability and biological
      theories of aging. The relative simplicity of the mixture distribution makes
      feasible a technique where the curvature functions of the corresponding survival
      and hazard rate functions are used to identify the beginning and the end of
      various life phases, such as infant mortality, the end of the force of natural
      selection, and late life mortality deceleration. We illustrate our results with a
      comparative analysis of Canadian and Indonesian mortality data.

PMID- 17188717
TI  - Detection of gamma-hydroxybutyrate in striatal microdialysates following
      peripheral 1,4-butanediol administration in rats.
AB  - The illicit use and abuse of 1,4-butanediol (1,4-BD) results from its presumed
      conversion to gamma-hydroxybutyrate (GHB) and subsequent pharmacological effects
      via action on GABA-B and GHB-specific receptors. Using in vivo microdialysis we
      measured the appearance of GHB in the striata of rats after peripheral 1,4-BD
      administration. We developed and utilized an HPLC-UV (215 nm) detection of GHB
      that yielded a limit of quantification (S/N=10) of 2.0 micro g/mL (40
      ng/injection) and a limit of detection (S/N=3) of 0.75 micro g/mL (15
      ng/injection). GHB appeared in the striatal microdialysates within 20 min after
      intraperitoneal (i.p.) administration of varying doses of 1,4-BD. GHB
      concentrations reached dose-dependent maxima 80-100 min post-1,4-BD
      administration, with peak values of 10.6+/-2.9, 25.3+/-3.4 and 48.1+/-7.1 micro
      g/mL (mean+/-S.E.M.), corresponding to 1,4-BD doses of 250, 500 and 750 mg/kg,
      respectively. The conversion of 1,4-BD to GHB was completely prevented by the
      alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP), administered prior to 1,4
      BD, as evidenced by the failure of GHB to appear in the striatal microdialysates.
      Sleep times in animals were similarly correlated with GHB concentrations in the
      microdialysates.

PMID- 17188718
TI  - Amelioration of dextran sulfate sodium-induced colitis in mice by oral
      administration of beta-caryophyllene, a sesquiterpene.
AB  - beta-Caryophyllene (BCP), a naturally occurring plant sesquiterpene, was examined
      for anti-inflammatory activity in a mouse model of experimental colitis induced
      by dextran sulfate sodium (DSS). Colitis was induced by exposing male BALB/c mice
      to 5% DSS in drinking water for 7 days. BCP in doses of 30 and 300 mg/kg was
      administered orally once a day, beginning concurrently with exposure to DSS. The
      body weight and colon length were measured, and histological damage and
      myeloperoxidase (MPO) activity as well as inflammatory cytokines were assessed in
      both serum and colonic tissue after 7 days of treatment with DSS. The DSS
      treatment damaged the colonic tissue, increased MPO activity and inflammatory
      cytokines, lowered the body weight, and shortened the length of the colon. Oral
      administration of BCP at 300 mg/kg significantly suppressed the shortening of
      colon length and slightly offset the loss of body weight. BCP treatment (300
      mg/kg) also significantly reduced the inflammation of colon and reversed the
      increase in MPO activity that had been induced by exposure to DSS. Further, BCP
      significantly suppressed the serum level of IL-6 protein (a 55% reduction) as
      well as the level of IL-6 mRNA in the tissue. These results demonstrate that BCP
      ameliorates DSS-induced experimental colitis, and may be useful in the prevention
      and treatment of colitis.

PMID- 17188720
TI  - Lymphangiogenesis following obstruction of large postnodal lymphatics in sheep.
AB  - We examined the impact of lymph flow obstruction in large post-nodal lymphatic
      vessels in sheep. A silk ligature was placed 2 cm downstream from the prescapular
      or popliteal lymph node and tightened to interrupt flow. At 6, 12 and 16 weeks
      after lymph flow blockage, a network of small interconnecting lymphatics
      (approximately 10-40 microm in diameter) could be observed in the vicinity of the
      ligature. These were identified using antibodies to the lymphatic endothelial
      markers LYVE-1 or VEGFR-3 or unequivocally, with the upstream intraluminal
      injection of the non-specific cell dye CFDA-SE. The observed lymphangiogenesis
      coincided with increased levels of Prox1, Tie2 (Y992) phosphorylation, MAPK
      activation, and decreased Akt activition. In the popliteal preparations, saline
      was infused into the prenodal ducts upstream of the regeneration site. The slopes
      of the inflow pressure versus flow relationships were 17.3+/-3.6, immediately
      after vessel obstruction, 36.2+/-9.6 at 6 weeks and 15.0+/-5.3 at 12-16 weeks.
      For comparison, the average slope in a completely intact popliteal system was
      3.1+/-0.3 (from a previous publication). The resistance to flow remained high up
      to 12-16 weeks after flow obstruction suggesting that normal flow parameters had
      not been achieved over this time. The lymph node appeared to have some role in
      limiting the impact of post-nodal lymph obstruction, a function that appeared to
      be compromised by lymph stasis.

PMID- 17188719
TI  - Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD
      activity and elevation of ROS/NADPH oxidase activity.
AB  - Neuronal apoptosis is a very important event in the development of the central
      nervous system (CNS), but the underlying mechanisms remain to be elucidated. We
      have previously shown that safrole oxide, a small molecule, induces integrin
      beta4 expression and promotes apoptosis in vascular endothelial cells. In this
      study, the effects of safrole oxide on cell growth and apoptosis have been
      examined in primary cultures of mouse neurons. Safrole oxide was found to
      significantly inhibit neuronal cell growth and to induce apoptosis. The
      inhibitory and apoptotic activities of safrole oxide followed a dose- and time
      dependent manner. Interestingly, the expression of integrin beta4 was
      significantly inhibited with safrole oxide treatment. Furthermore, safrole oxide
      dramatically increases the level of intracellular reactive oxygen species (ROS)
      and the activity of NADPH oxidase. Moreover, manganese-dependent superoxide
      dismutase (MnSOD) activity was decreased significantly with safrole oxide
      treatment. Our study thus demonstrates that safrole oxide induces neuronal
      apoptosis through integrin beta4, ROS, NADPH, and MnSOD.

PMID- 17188721
TI  - Behavioral and neurophysiological responses of European sea bass groups reared
      under food constraint.
AB  - The individual food-demand behavior of juvenile European sea bass (Dicentrarchus
      labrax, L.) reared in groups under self-feeding conditions was investigated. The
      triggering activity on self-feeder, i.e. index of the food-demand activity,
      agonistic interactions and territorial behavior were monitored for periods of 42
      to 68 days in six groups of 50 fish. The specific growth rate was calculated and
      the brain serotonergic activity was used as a stable index of social stress.
      Inter-individual differences appeared in triggering activity and three groups
      were distinguished: 3-5 high-triggering fish, 17-30 low-triggering fish and the
      remaining individuals were null-triggering fish. There were no significant
      differences in specific growth rates calculated at the end of the experiment (day
      42 or day 68) between individuals with high, low, and null food-demand (ANOVA,
      p>0.05). No territorial or agonistic behaviors were observed, however, there were
      significant differences in brain serotonergic activity between the three
      triggering groups (ANOVA, p=0.050 in telencephalon and p=0.004 in cerebellum).
      Specifically, high-triggering fish had lower serotonergic turnover than low or
      null-triggering fish. We put forth the hypothesis that fish with low or null
      triggering activity could be stressed by the high activity of high-triggering
      individuals.

PMID- 17188722
TI  - 10-Phenyl-[11]-cytochalasans from Indonesian mushroom Microporellus subsessilis.
AB  - 10-Phenyl-[11]-cytochalasans (4-6), together with three known derivatives (1-3),
      were isolated from the MeOH extract of the Indonesian mushroom Microporellus
      subsessilis by a bioassay-guided fractionation. The compounds 6 and 1-3 induced
      immotility in Artemia salina.

PMID- 17188723
TI  - The diversity of pathogenesis-related proteins decreases during grape maturation.
AB  - It was recently shown that wines contain typically a huge diversity of
      structurally similar polypeptides that exhibit a high degree of homology to
      pathogenesis-related (PR) proteins. This observation suggested the existence of
      one or a few precursors in mature grapes, common to most or all the wine PR
      proteins. Limited proteolysis and chemical modification of the precursor(s)
      during fruit ripening and winemaking could then generate the large number of
      distinct wine polypeptides. However, the patterns of PR proteins extracted from
      grape berries regularly harvested from the onset of development until maturity
      did not confirm the previous hypothesis. Two different methodologies, involving 2
      D immunoblotting and a combination of FPLC cation/anion exchange chromatographies
      with 1-D immunoblotting, indicate that the total concentration of PR proteins is
      increased but its diversity is reduced from the early stages of berry development
      until maturity. These results indicate that PR proteins are synthesized in a wide
      variety of forms from the early stages of grape development, eliminating the
      hypothesis previously formulated on the existence of one or few precursors common
      to the wine proteins.

PMID- 17188724
TI  - Associations between the metabolic syndrome and its components, watching
      television and physical activity.
AB  - OBJECTIVE: To examine the associations between watching television and physical
      activity with the metabolic syndrome and its components. STUDY DESIGN: Cross
      sectional study. METHODS: This study was conducted among 358 subjects recruited
      from the Department of Health Management of Chang Gung Medical Centre in Linkou.
      After adjustment for gender, age and body mass index (BMI), the odds ratios (ORs)
      of the metabolic syndrome and its components were analysed for relative daily
      energy expenditure groups and time spent watching television categories. RESULTS:
      After adjustment for gender, age and BMI, the OR of the metabolic syndrome in the
      most active subjects compared with the least active subjects was 0.27 [95%
      confidence interval (CI)=0.08-0.88; P=0.030]. There was inconclusive evidence of
      an association between watching television for more than 20h/week and presence of
      the metabolic syndrome (OR=2.99; 95% CI=0.83-10.84; P=0.095). CONCLUSIONS:
      Physical activity was a significant protective factor for presence of the
      metabolic syndrome and low levels of high-density-lipoprotein cholesterol.
      Watching television was positively associated with greater odds of high levels of
      triglycerides and fasting glucose. This study emphasized the importance of
      reducing the time spent watching television and increasing the level of physical
      activity for prevention of the metabolic syndrome.

PMID- 17188725
TI  - Regulation of expression of 1,25D3-MARRS/ERp57/PDIA3 in rat IEC-6 cells by TGF
      beta and 1,25(OH)2D3.
AB  - We examined the transcriptional regulation of expression of the redox-sensitive
      Membrane-Associated-Rapid Response, Steroid-binding (1,25D(3)-MARRS) protein
      specific for 1,25(OH)(2)D(3) in a rat small intestinal cell line, IEC-6, that
      demonstrates rapid responses to 1,25(OH)(2)D(3). 1,25D(3)-MARRS binds and is
      activated by 1,25(OH)(2)D(3), but is not itself up-regulated by treatment with
      1,25(OH)(2)D(3), nor is there a Vitamin D response element (VDRE) in its proximal
      promoter. We previously reported that transforming growth factor beta (TGFbeta)
      increased steady state levels of 1,25D(3)-MARRS transcript and protein
      approximately two-fold [Rohe B, Safford SE, Nemere I, Farach-Carson, MC.
      Identification and characterization of 1,25D(3)-membrane-associated rapid
      response, steroid (1,25D(3)-MARRS)-binding protein in rat IEC-6 cells. Steroids
      2005;70:458-63]. To determine if this up-regulation could be attributed to the
      function of a highly conserved consensus smad 3 binding element present in the
      proximal promoter of the 1,25D(3)-MARRS gene, we created a promoter-reporter
      [SEAP] construct that was responsive to TGFbeta (200 pM). Deletion or mutation of
      the smad 3 element greatly reduced the response of the 1,25D(3)-MARRS promoter to
      TGFbeta. Subsequent studies found that the smad 3 response element is bound by a
      protein found in the IEC-6 nuclear extract, most likely smad 3. Interestingly,
      although 1,25(OH)(2)D(3) alone did not increase expression of the 1,25D(3)-MARRS
      promoter-reporter, co-treatment of transfected IEC-6 cells with 1,25(OH)(2)D(3)
      and TGFbeta shifted the dose-response curve to a lower effective concentration
      (100 pM peptide). We conclude that TGFbeta is a transcriptional regulator of
      1,25D(3)-MARRS expression via a functional smad 3 element and that cross-talk
      with non-classical 1,25(OH)(2)D(3)-stimulated pathways occurs. The findings have
      broad implications for redox-sensitive signaling phenomena including those that
      regulate phosphate transport in the intestine.

PMID- 17188726
TI  - Stimulatory effect of oral administration of tea, coffee or caffeine on UVB
      induced apoptosis in the epidermis of SKH-1 mice.
AB  - Oral administration of green tea or a caffeine solution, but not decaffeinated
      green tea, inhibits UVB-induced complete carcinogenesis in SKH-1 mice. Oral
      administration of green tea, coffee or a caffeine solution for 2 weeks enhanced
      UVB-induced increases in apoptosis in the epidermis, but these treatments had no
      effect in non-UVB treated normal epidermis. Our results suggest that
      administration of green tea, coffee and caffeine may inhibit UVB-induced
      carcinogenesis--at least in part--by enhancing UVB-induced apoptosis. Plasma
      levels of caffeine observed after its oral administration at cancer-preventive
      dose levels were within the range observed in moderate coffee drinkers. Topical
      applications of caffeine to mice previously treated with UVB for 20 weeks (high
      risk mice without tumors) inhibited the formation of tumors and stimulated
      apoptosis in the tumors but not in areas of the epidermis away from tumors. The
      selective effects of caffeine administration to stimulate UVB-induced apoptosis
      or apoptosis in tumors but not in normal epidermis or in areas of the epidermis
      away from tumors is of considerable interest, but the reasons for the selective
      effects of caffeine on apoptosis in DNA damaged tissues are unknown. Further
      studies are needed to determine mechanisms of these effects of caffeine and to
      determine the effects of caffeine administration on sunlight-induced actinic
      keratoses and squamous cell carcinomas in humans.

PMID- 17188727
TI  - Medical countermeasure against respiratory toxicity and acute lung injury
      following inhalation exposure to chemical warfare nerve agent VX.
AB  - To develop therapeutics against lung injury and respiratory toxicity following
      nerve agent VX exposure, we evaluated the protective efficacy of a number of
      potential pulmonary therapeutics. Guinea pigs were exposed to 27.03 mg/m(3) of VX
      or saline using a microinstillation inhalation exposure technique for 4 min and
      then the toxicity was assessed. Exposure to this dose of VX resulted in a 24-h
      survival rate of 52%. There was a significant increase in bronchoalveolar lavage
      (BAL) protein, total cell number, and cell death. Surprisingly, direct pulmonary
      treatment with surfactant, liquivent, N-acetylcysteine, dexamethasone, or anti
      sense syk oligonucleotides 2 min post-exposure did not significantly increase the
      survival rate of VX-exposed guinea pigs. Further blocking the nostrils, airway,
      and bronchioles, VX-induced viscous mucous secretions were exacerbated by these
      aerosolized treatments. To overcome these events, we developed a strategy to
      protect the animals by treatment with atropine. Atropine inhibits muscarinic
      stimulation and markedly reduces the copious airway secretion following nerve
      agent exposure. Indeed, post-exposure treatment with atropine methyl bromide,
      which does not cross the blood-brain barrier, resulted in 100% survival of VX
      exposed animals. Bronchoalveolar lavage from VX-exposed and atropine-treated
      animals exhibited lower protein levels, cell number, and cell death compared to
      VX-exposed controls, indicating less lung injury. When pulmonary therapeutics
      were combined with atropine, significant protection to VX-exposure was observed.
      These results indicate that combinations of pulmonary therapeutics with atropine
      or drugs that inhibit mucous secretion are important for the treatment of
      respiratory toxicity and lung injury following VX exposure.

PMID- 17188728
TI  - Arsenic-induced toxicity and the protective role of ascorbic acid in mouse
      testis.
AB  - Oxidative stress has been suggested to be a major cause of male reproductive
      failure. Here, we investigated whether arsenic, which impairs male reproductive
      functions in rodent models, acts by inducing oxidative stress. Male 8-week-old
      ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with
      or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The
      arsenic-treated mice showed decreased epididymidal sperm counts and testicular
      weights compared to untreated mice. These effects were reversed in mice that were
      co-treated with ascorbic acid. Similarly, arsenic treatment lowered the
      activities of testicular 3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD,
      which play important roles in steroidogenesis, and this was reversed by co
      treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased
      glutathione (GSH) levels (which correlate inversely with the degree of cellular
      oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative
      damage to tissue proteins). Ascorbic acid co-treatment reversed both of these
      effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male
      reproductive functions and the arsenic-induced testicular oxidative changes.
      These observations support the notion that arsenic impairs male reproductive
      function by inducing oxidative stress.

PMID- 17188729
TI  - A mode of action for induction of liver tumors by Pyrethrins in the rat.
AB  - High doses of Pyrethrins produce liver tumors in female rats. To elucidate the
      mode of action for tumor formation, the hepatic effects of Pyrethrins have been
      investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control)
      and 8000 ppm Pyrethrins and female rats' diets containing 0, 100, 3000 and 8000
      ppm Pyrethrins for periods of 7, 14 and 42 days and 42 days followed by 42 days
      of reversal. As a positive control, rats were also fed diets containing 1200-1558
      ppm sodium Phenobarbital (NaPB) for 7 and 14 days. The treatment of male rats
      with 8000 ppm Pyrethrins, female rats with 3000 and 8000 ppm Pyrethrins and both
      sexes with NaPB resulted in increased liver weights, which were associated with
      hepatocyte hypertrophy. Hepatocyte replicative DNA synthesis was also increased
      by treatment with Pyrethrins and NaPB. The treatment of male and female rats with
      Pyrethrins and NaPB produced significant increases in hepatic microsomal
      cytochrome P450 (CYP) content and a marked induction of CYP2B-dependent 7
      pentoxyresorufin O-depentylase and testosterone 16beta-hydroxylase activities.
      Significant increases were also observed in CYP3A-dependent testosterone 6beta
      hydroxylase activity. The hepatic effects of Pyrethrins were dose-dependent in
      female rats with 100 ppm being a no effect level and on cessation of treatment
      were reversible in both sexes. This study demonstrates that Pyrethrins are
      mitogenic CYP2B form inducers in rat liver. The mode of action for Pyrethrins
      induced rat liver tumor formation appears to be similar to that of NaPB and some
      other non-genotoxic CYP2B inducers of hepatic xenobiotic metabolism.

PMID- 17188730
TI  - Sexually dimorphic gene regulation in brain as a target for endocrine disrupters:
      developmental exposure of rats to 4-methylbenzylidene camphor.
AB  - The developing neuroendocrine brain represents a potential target for endocrine
      active chemicals. The UV filter 4-methylbenzylidene camphor (4-MBC) exhibits
      estrogenic activity, but also interferes with the thyroid axis. We investigated
      effects of pre- and postnatal exposure to 4-MBC in the same rat offspring at
      brain and reproductive organ levels. 4-MBC (7, 24, 47 mg/kg/day) was administered
      in chow to the parent generation before mating, during gestation and lactation,
      and to the offspring until adulthood. mRNA of estrogen target genes involved in
      control of sexual behavior and gonadal functions was measured by real-time RT-PCR
      in ventromedial hypothalamic nucleus (VMH) and medial preoptic area (MPO) of
      adult offspring. 4-MBC exposure affected mRNA levels of ER alpha, progesterone
      receptor (PR), preproenkephalin (PPE) and insulin-like growth factor-I (IGF-I) in
      a sex- and region-specific manner. In order to assess possible changes in
      sensitivity of target genes to estrogens, offspring were gonadectomized on day
      70, injected with estradiol (E2, 10 or 50 microg/kg s.c.) or vehicle on day 84,
      and sacrificed 6 h later. The acute induction of PR mRNA, and repression (at 6 h)
      of PPE mRNA by E2 was enhanced by 4-MBC in male and female VMH and female MPO,
      whereas male MPO exhibited reduced responsiveness of both genes. Steroid receptor
      coactivator SRC-1 mRNA levels were increased in female VMH and MPO. The data
      indicate profound sex- and region-specific alterations in the regulation of
      estrogen target genes at brain level. Effect patterns in baseline and E2-induced
      gene expression differ from those in uterus and prostate.

PMID- 17188731
TI  - Distribution of tetrodotoxin in the body of the blue-ringed octopus
      (Hapalochlaena maculosa).
AB  - Tetrodotoxin (TTX) was quantitatively assayed in six specimens of semi-adult blue
      ringed octopus, Hapalochlaena maculosa, by a post-column fluorescent-HPLC system.
      TTX was found to be present in all body parts, e.g. in high concentrations in the
      arms followed by the abdomen and cephalothorax. The toxin is not associated
      exclusively with the posterior salivary gland.

PMID- 17188732
TI  - Kallikrein-kinin system activation by Lonomia obliqua caterpillar bristles:
      involvement in edema and hypotension responses to envenomation.
AB  - Lonomia obliqua envenomation induces an intense burning sensation at the site of
      contact and severe hemorrhage followed by edema and hypotension, and after few
      days death can occur usually due to acute renal failure. In order to understand
      more about the envenomation syndrome, the present study investigates the role
      played by kallikrein-kinin system (KKS) in edematogenic and hypotensive responses
      to the envenomation by L. obliqua. The incubation of L. obliqua caterpillar
      bristles extract (LOCBE) with plasma results in kallikrein activation, measured
      by cromogenic assay using the kallikrein synthetic substrate S-2302 (H-D-Pro-Phe
      Arg-pNA). It was also showed that LOCBE was able to release kinins from low
      molecular weight kininogen (LMWK). Moreover, it was demonstrated that previous
      administration of a kallikrein inhibitor (aprotinin) or bradykinin B2 receptor
      antagonist (HOE-140) significantly reduces the edema and hypotension in response
      to LOCBE, using mouse paw edema bioassay and mean arterial blood pressure
      analysis, respectively. The results demonstrate a direct involvement of the KKS
      in the edema formation and in the fall of arterial pressure that occur in the L.
      obliqua envenomation syndrome.

PMID- 17188734
TI  - Increases in fecal coliform bacteria resulting from centrifugal dewatering of
      digested biosolids.
AB  - In many countries, the classification of biosolids for disposal purposes can be
      based, in part, on fecal coliform levels, with alternative criteria also
      available based on the stabilization process used, such as anaerobic digestion.
      The assumption that these alternative criteria provide equivalent protection may
      be flawed. This paper demonstrates that fecal coliform levels determined after
      digestion do not always indicate the bacterial levels after the same biosolids
      have been dewatered by centrifugation. In samples from mesophilic digestion, half
      had significant increases in coliform numbers (P<0.05) with up to one order of
      magnitude increase during centrifugation, suggesting coliform regrowth.
      Thermophilically digested samples had significant increases of several orders of
      magnitude during dewatering, more likely from reactivation of viable but non
      culturable coliforms than from regrowth. In other cases, centrifugation induced
      coliform regrowth or reactivation upon incubation and storage of dewatered
      samples, but not digested samples. These 2-3 order of magnitude increases
      occurred with both 25 and 37 degrees C incubations. Coliform increases continued
      for up to 5 days, then gradually declined. However, by day 20 coliform numbers
      were still 2 orders of magnitude greater than when originally sampled. The
      magnitude of the increases could be due either to regrowth or reactivation, but
      the nature of the longer-term increases--also seen in biosolids/soil mixtures-
      suggests regrowth. Differences in numbers between digested and dewatered samples
      could not be duplicated with high shear processing in lab-scale devices, with
      nitrogen purging to remove volatile or gaseous constituents, or with redilution
      using centrate. They could not be attributed to enumeration methods, to
      interference of Bacillus spp. on apparent coliform counts, or to temperature
      changes. The increases have practical implications in the use of fecal coliform
      or alternative criteria to define pathogen content in biosolids.

PMID- 17188735
TI  - Ozonation reduces sludge production and improves denitrification.
AB  - The effectiveness of partial ozonation of return activated sludge for enhancing
      denitrification and waste sludge minimization were examined. A pair of nitrifying
      sequencing batch reactors was operated in either aerobic or alternating
      anoxic/aerobic conditions, with one control and one ozonated reactor in each set.
      The amount of solids produced decreased with the ozone dose. Biomass in the
      anoxic/aerobic reactor was easier to destroy (up to 25% of the initial excess
      sludge) than in the aerobic (10%) one, generating approximately twice as much
      soluble COD by cell lysis. Denitrification rate improved up to 60% due to
      additional carbon released by ozonation. Nitrification rates deteriorated much
      more in the aerobic than in the alternating reactor, possibly as a result of
      direct destruction of nitrifying autotrophs as well as competition created by
      growth of heterotrophs receiving the additional COD. Overall, ozonation provided
      the expected benefits in denitrification and had less impact on nitrification in
      the alternating reactors.

PMID- 17188736
TI  - Influence of hydrodynamic conditions on the start-up of methanogenic inverse
      turbulent bed reactors.
AB  - The influence of hydrodynamic conditions on the start-up phase of an inverse
      turbulent bed bioreactor was investigated. Two identical reactors, differing only
      by the gas velocity ensuring the carrier fluidization and generating the main
      hydrodynamic strengths (attrition), were monitored. Regarding the first 96 days,
      the experiments showed better performances for the reactor having the lowest
      hydrodynamic strengths. These results were correlated to lower attached biomass
      and higher biofilm specific removal rate for the reactor subjected to strong
      hydrodynamic strengths. Once the start-up was completed and the reactor
      stabilized at an organic loading rate of 6g(COD)L(-1)d(-1), the same hydrodynamic
      strengths were applied (gas velocity was equalized). The results proved that
      hydrodynamic conditions make it possible to control the biofilm characteristics.
      Consequently, it should be recommended to apply minimal strengths to enhance the
      biofilm growth during the early start-up phase, and then to increase them to
      control biofilm thickness and to optimize the reactor performances.

PMID- 17188733
TI  - B5-deficient vaccinia virus as a vaccine vector for the expression of a foreign
      antigen in vaccinia immune animals.
AB  - Recombinant vaccinia viruses have shown promise as vaccine vectors. However,
      their effectiveness is markedly reduced by pre-existing anti-vaccinia immunity.
      The possibility of new vaccinia immunizations in the event of a bioterror-related
      smallpox release poses an additional negative impact on the utility of vaccinia
      based vectors. Thus, we aimed to design a vaccinia vector that would enhance the
      immune response to an expressed foreign protein in a pre-immune animal model. To
      do this, we made use of the finding that most neutralizing antibodies against the
      extracellular form of vaccinia virus are directed against the B5 protein. We
      found that mice immunized with vaccinia, primed with Gag plasmid DNA, and boosted
      with a recombinant vaccinia virus lacking the majority of the B5 ectodomain
      expressing a test antigen, HIV Gag, had stronger anti-Gag immune responses than
      mice that were boosted with a wild-type virus-expressing Gag. These findings are
      particularly striking given the more attenuated phenotype of this virus, as
      compared to its wild-type counterpart. Importantly, we found that vaccination
      with a B5R deletion virus, followed by boosting with the Gag-expressing virus
      lacking the majority of the B5 ectodomain, resulted in poorer anti-Gag immune
      responses. Thus, recombinant vaccinia viruses lacking the B5 ectodomain may serve
      as vaccine vectors in DNA prime-vaccinia boost vaccinations of individuals with
      pre-existing immunity against vaccinia. These data open the possibility of
      extending the potential benefit of replication competent recombinant vaccinia
      virus vectors to a larger population.

PMID- 17188737
TI  - Simulating the evolution of non-point source pollutants in a shallow water
      environment.
AB  - Non-point source pollution originating from surface applied chemicals in either
      liquid or solid form as part of agricultural activities, appears in the surface
      runoff caused by rainfall. The infiltration and transport of these pollutants has
      a significant impact on subsurface and riverine water quality. The present paper
      describes the development of a unified 2-D mathematical model incorporating
      individual models for infiltration, adsorption, solubility rate, advection and
      diffusion, which significantly improve the current practice on mathematical
      modeling of pollutant evolution in shallow water. The governing equations have
      been solved numerically using cubic spline integration. Experiments were
      conducted at the Hydrodynamics Laboratory of the Ecole Polytechnique de Montreal
      to validate the mathematical model. Good correspondence between the computed
      results and experimental data has been obtained. The model may be used to predict
      the ultimate fate of surface applied chemicals by evaluating the proportions that
      are dissolved, infiltrated into the subsurface or are washed off.

PMID- 17188738
TI  - Relations between PM10 composition and cell toxicity: a multivariate and
      graphical approach.
AB  - Previous studies have used particle mass and size as metrics to link airborne
      particles with deleterious health effects. Recent evidence suggests that particle
      composition can play an important role in PM-toxicity; however, little is known
      about the specific participation of components (individually or acting in groups)
      present in such a complex mixture that accounts for toxicity. This work explores
      relationships among PM(10) components in order to identify their covariant
      structure and how they vary in three sites in Mexico City. Relationships between
      PM(10) with cell toxicity and geographical location were also explored. PM(10)
      was analyzed for elemental composition, organic and elemental carbon, endotoxins
      and the induction of inhibition of cell proliferation, IL-6, TNFalpha and p53.
      PM(10) variables were evaluated with principal component analysis and one-way
      ANOVA. The inhibition of cell proliferation, IL-6 and TNFalpha were evaluated
      with factorial ANOVA and p53 with the Welch test. The results indicate that there
      is heterogeneity in particle mass, composition and toxicity in samples collected
      at different sites. Multivariate analysis identified three major groups: (1)
      S/K/Ca/Ti/Mn/Fe/Zn/Pb; (2) Cl/Cr/Ni/Cu; and (3) endotoxins, organic and elemental
      carbon. Groups 1 and 3 showed significant differences among sites. Factorial
      ANOVA modeling indicated that cell proliferation was affected by PM
      concentration; TNFalpha and IL-6 by the interaction of concentration and site,
      and p53 was different by site. Radial plots suggest the existence of complex
      interactions between components, resulting in characteristic patterns of toxicity
      by site. We conclude that interactions of PM(10) components determine specific
      cellular outcomes.

PMID- 17188739
TI  - Discovery of new open-air Paleolithic localities in Central Alborz, Northern
      Iran.
AB  - The cooperative French-Iranian Paleoanthropological Project (FIPP) discovered
      three Paleolithic localities in Central Alborz, Northern Iran during its 2005
      field mission. In the northern foothills near Baliran in Mazandaran province,
      Garm Roud yielded an open-air site with an archaeological layer attributable to
      the last glacial period that dates from the end of OIS 3 (28,486+/-190 cal BP).
      These geochronological data and the typo-technical observations converge to place
      the Garm Roud 2 assemblage in the Upper Paleolithic. Garm Roud 2 is thus the
      first site of this kind discovered in the area. In the southern foothills near
      Damavand in Tehran province, Moghanak and Otchounak represent two open-air
      surface localities with lithic assemblages of Mousterian to Ante-Mousterian
      affinity. Garm Roud, Moghanak, and Otchounak provide some of the first direct
      field evidence of early human settlements in this central area of the Middle
      East.

PMID- 17188741
TI  - Homocysteine, reactive oxygen species and nitric oxide in type 2 diabetes
      mellitus.
AB  - INTRODUCTION: Type 2 diabetes mellitus shows a characteristic altered platelet
      function that can be due to several mechanisms such as oxidative stress.
      Hyperhomocysteinemia, considered as a risk factor for various arterial
      thrombosis, may have a role in generating oxidative damage, even if the
      pathogenic mechanisms are still not clear. In this report we aimed to determine
      the role of plasma homocysteine in inducing oxidative stress in type 2 diabetes
      mellitus. MATERIALS AND METHODS: The study was performed on a group of 34 males
      with type 2 diabetes and 36 healthy subjects matched for sex and age. Patients
      and healthy subjects were undergone to laboratory evaluation for plasma
      homocysteine levels and other metabolic parameters. In both groups of subjects
      platelet reactive oxygen species, nitric oxide and guanosine 3',5' cyclic
      monophosphate levels were measured. Moreover the reduced glutathione content in
      platelets of patients and of healthy subjects was assayed. RESULTS: Plasma
      homocysteine levels were significantly increased in patients compared with
      healthy subjects. The basal level of reactive oxygen species was significantly
      higher in patients than in controls. In addition platelets of patients stimulated
      with thrombin produced more reactive oxygen species than healthy subjects ones.
      The nitric oxide, guanosine 3',5' cyclic monophosphate and reduced glutathione
      content were decreased in platelets of patients. CONCLUSIONS: As homocysteine
      stimulates oxidative stress and inhibits nitric oxide formation,
      hyperhomocysteinemia measured in type 2 diabetic patients, promoting platelet
      hyperactivity, could have a role in the atherogenic effects described in type 2
      diabetes.

PMID- 17188740
TI  - Protease activation of calcium-independent phospholipase A2 leads to neutrophil
      recruitment to coronary artery endothelial cells.
AB  - INTRODUCTION: Thrombin or tryptase cleavage of protease-activated receptors (PAR)
      on human coronary artery endothelial cells (HCAEC) results in activation of a
      membrane-associated, calcium-independent phospholipase A2 (iPLA2) that
      selectively hydrolyzes plasmalogen phospholipids. Atherosclerotic plaque rupture
      results in a coronary ischemic event in which HCAEC in the ischemic area would be
      exposed to increased thrombin concentrations in addition to tryptase released by
      activated mast cells present in the plaque. MATERIALS AND METHODS: HCAEC were
      stimulated with thrombin or tryptase in the absence or presence of bromoenol
      lactone (BEL), a selective iPLA2 inhibitor, and iPLA2 activation, accumulation of
      biologically active membrane phospholipid-derived metabolites, upregulation of
      cell surface P-selectin expression and neutrophil adherence were measured.
      RESULTS: HCAEC exposed to thrombin or tryptase stimulation demonstrated an
      increase in iPLA2 activity and arachidonic acid release. Additionally, stimulated
      HCAEC demonstrated increased platelet-activating factor (PAF) production and cell
      surface P-selectin expression, resulting in increased adhesion of neutrophils to
      HCAEC monolayers. Pretreatment with bromoenol lactone to inhibit iPLA2, blocked
      membrane phospholipid-derived metabolite production, increased cell surface P
      selectin expression and neutrophil adherence. CONCLUSIONS: The similar
      biochemical and cellular responses in HCAEC exposed to thrombin or tryptase
      stimulation suggest that the cleavage of two separate PAR serve to extend the
      range of proteases to which the cells respond rather than resulting in separate
      intracellular events. This suggests that in conditions such as thrombosis and
      atherosclerosis that multiple mechanisms can activate the inflammatory response.

PMID- 17188742
TI  - The effect of the 5-HT1A receptor agonist, 8-OH-DPAT, on motion-induced emesis in
      Suncus murinus.
AB  - In the present study we evaluated the role of 5-HT(1A) receptors in mediating the
      inhibitory action of 8-OH-DPAT, a 5-HT(1A) receptor agonist, in motion sickness
      in Suncus murinus. 8-OH-DPAT (0.1 mg/kg, i. p) attenuated motion-induced emesis
      which was associated with an increase in the latency of the onset to the first
      emetic episode. Pre-treatment with methysergide (a 5-HT(1/2/7) receptor
      antagonist, 1.0 mg/kg, i. p.), WAY-100635 (a 5-HT(1A) receptor antagonist, 1.0
      mg/kg, i. p.), SB269970A (a 5-HT(7) receptor antagonist, 1.0 and 5.0 mg/kg, i.
      p.), ondansetron (a 5-HT(3) receptor antagonist, 1.0 mg/kg, i. p) or GR13808 (a 5
      HT(4) receptor antagonist, 0.5 mg/kg, i. p) failed to modify the inhibitory
      action of 8-OH-DPAT on motion sickness. Furthermore, the application of either
      methysergide, WAY-100635, SB269970A, ondansetron or GR13808 alone had no effect
      on motion sickness in its own right. These data indicate that neither 5-HT(1A)
      nor any 5-HT(2) receptor subtypes, 5-HT(3), 5-HT(4) and 5-HT(7) receptors are
      likely to be involved in the inhibition of motion-induced emesis mediated by 8-OH
      DPAT.

PMID- 17188743
TI  - Association between illicit drug and alcohol use and first manic episode.
AB  - In light of the established influence of substance use on the onset, course, and
      outcome of bipolar disorder, we performed a retrospective chart review of
      patients with bipolar I disorder participating in a randomized controlled trial
      to further investigate the relationship between alcohol and substance use and
      first onset of mania. A total of 59.4% (N=101) of the 170 participants were
      determined to have a history of substance and/or alcohol use. Among the 101
      participants with SU, use was coded in 10 (9.9%) as immediately preceding, in 50
      (49.5%) as preceding mania, in 7 (6.9%) as following mania, and in 34 (33.7%) as
      indeterminable. Of the 10 participants with immediately preceding use, 5
      experienced their first manic episode immediately after discontinuing a
      substance. Our findings support earlier reports detailing the high prevalence of
      substance use among patients with bipolar disorder. Treatments targeting alcohol
      and substance use among individuals with bipolar disorder are clearly needed, as
      are prophylactic treatments targeting adolescents and young adults who are at
      risk for either bipolar disorder or alcohol and substance related disorders.

PMID- 17188744
TI  - Relationships among lipid peroxidation, glutathione peroxidase, superoxide
      dismutase, sperm parameters, and competitive index in dairy bulls.
AB  - Sperm membranes contain high concentrations of polyunsaturated fatty acids that
      are highly susceptible to oxidative damage that interferes with fertilization
      ability. The objective of this study was to determine associations among lipid
      peroxidation (thiobarbituric-acid-reactive substance concentration), antioxidant
      enzymatic activities in frozen spermatozoa, and competitive indices. Semen from
      multiple ejaculates collected in succession from each bull (four Holstein and
      four Jersey) was pooled. Heterospermic doses (20x10(6)sperm/0.5mL straw) were
      made to obtain 16 Holstein/Jersey combinations (equal number of sperm from each
      bull). Cows were inseminated on observed or synchronized estrus. The sire of
      calves (N=460) was determined; based on the number of calves sired, a competitive
      index was obtained for each bull. Prior to preparation of the heterospermic
      doses, a sub-sample of semen from each bull was taken, processed, frozen, and
      stored concurrent with heterospermic samples. After thawing, these homospermic
      samples were assessed for lipid peroxidation, superoxide dismutase (SOD)
      activity, glutathione peroxidase (GPx) activity, DNA fragmentation index (DFI),
      plasma membrane integrity (PMI), and total progressive motility (assessed by
      CASA). Sperm lipid peroxidation and the competitive index were negatively
      correlated (r=-0.78; P<0.05), the DFI and sperm lipid peroxidation were
      positively correlated (r=0.86; P<0.001), and there were negative correlations
      (P<0.05) for sperm lipid peroxidation and both PMI and total progressive motility
      (r=-0.78 and -0.83, respectively). There was neither significant association
      between SOD activity and competitive index, nor between GPx activity and
      competitive index. In conclusion, bulls with lower sperm lipid peroxidation had
      higher chances of siring calves; this was attributed to the deleterious effects
      of lipid peroxidation on sperm plasma membrane integrity and sperm DNA, which may
      reduce sperm fertilizing potential.

PMID- 17188745
TI  - Microtensile bond strength of a resin cement to feldpathic ceramic after
      different etching and silanization regimens in dry and aged conditions.
AB  - OBJECTIVES: This study evaluated the durability of bond strength between resin
      cement and a feldspathic ceramic submitted to different etching regimens with and
      without silane coupling agent application. METHODS: Thirty-two blocks (6.4 mm x
      6.4 mm x 4.8 mm) were fabricated using a microparticulate feldspathic ceramic
      (Vita VM7), ultrasonically cleaned with water for 5 min and randomly divided into
      four groups, according to the type of etching agent and silanization method:
      method 1, etching with 10% hydrofluoric (HF) acid gel for 1 min + silanization;
      method 2, HF only; method 3, etching with 1.23% acidulated phosphate fluoride
      (APF) for 5 min + silanization; method 4, APF only. Conditioned blocks were
      positioned in their individual silicone molds and resin cement (Panavia F) was
      applied on the treated surfaces. Specimens were stored in distilled water (37
      degrees C) for 24h prior to sectioning. After sectioning the ceramic-cement
      blocks in x- and y-axis with a bonded area of approximately 0.6mm(2), the
      microsticks of each block were randomly divided into two storage conditions: Dry,
      immediate testing; TC, thermal cycling (12,000 times)+water storage for 150 d,
      yielding to eight experimental groups. Microtensile bond strength tests were
      performed in universal testing machine (cross-head speed: 1mm/min) and failure
      types were noted. Data obtained (MPa) were analyzed with three-way ANOVA and
      Tukey's test (alpha=0.05). RESULTS: Significant influence of the use of silane
      (p<0.0001), storage conditions (p=0.0013) and surface treatment were observed
      (p=0.0014). The highest bond strengths were achieved in both dry and thermocycled
      conditions when the ceramics were etched with HF acid gel and silanized (17.4 +/-
      5.8 and 17.4 +/- 4.8 MPa, respectively). Silanization after HF acid gel and APF
      treatment increased the results dramatically (14.5+/-4.2-17.4+/-4.8 MPa) compared
      to non-silanized groups (2.6 +/- 0.8-8.9 +/- 3.1 MPa) where the failure type was
      exclusively (100%) adhesive between the cement and the ceramic. SIGNIFICANCE:
      Silanization of the feldspathic ceramic surface after APF or HF acid etching
      increased the microtensile bond strength results significantly, with the latter
      providing higher results. Long-term thermocycling and water storage did not
      decrease the results in silanized groups.

PMID- 17188746
TI  - Time-dependent changes in adhesive force between chondrocytes and silk fibroin
      substrate.
AB  - In tissue engineering for cartilage repair using scaffold, initial chondrocyte
      material interactions are significantly important for the following cell
      behaviors such as phenotypic expression and matrix synthesis. Silk fibroin
      scaffold is considered to be one of the useful materials in/on which chondrocytes
      can proliferate without dedifferentiating into fibroblast-like cells and can
      organize a hyaline-like tissue. For the purpose of seeking some useful aspects
      for designing scaffold, initial adhesive force of chondrocytes to the surface of
      fibroin substrate was measured by using a lab-made apparatus applying the
      cantilever beam method. It was found that the adhesive force per unit spreading
      area of chondrocytes on fibroin substrate had a clear peak between 6 and 12h
      after seeding. From the results of immunofluorescence staining for actin and
      vinculin during this period, it could be thought that an immature formation of
      actin fibers which was uniquely observed at the periphery of cells attaching to
      fibroin substrate did not contribute to the increase of adhesive force. Results
      in this study suggested that surface of the fibroin substrate was gradually
      covered with some substances which inhibit the adhesion during this period. These
      cell-material interactions have a possibility to be useful information for
      designing the adhesive performance of scaffold surface in cartilage regeneration.

PMID- 17188747
TI  - Biocompatibility evaluation of silk fibroin with peripheral nerve tissues and
      cells in vitro.
AB  - Silk-based materials have been used in the field of bone or ligament tissue
      engineering. In order to explore the feasibility of using purified silk fibroin
      to construct artificial nerve grafts, it is necessary to evaluate the
      biocompatibility of silk fibroin material with peripheral nerve tissues and
      cells. We cultured rat dorsal root ganglia (DRG) on the substrate made up of silk
      fibroin fibers and observed the cell outgrowth from DRG during culture by using
      light and electron microscopy coupled with immunocytochemistry. On the other
      hand, we cultured Schwann cells from rat sciatic nerves in the silk fibroin
      extract fluid and examined the changes of Schwann cells after different times of
      culture. The results of light microscopy, MTT test and cell cycle analysis showed
      that Schwann cells cultured in the silk fibroin extract fluid showed no
      significant difference in their morphology, cell viability and proliferation as
      compared to that in plain L15 medium. Furthermore, no significant difference was
      found in expression of the factors secreted by Schwann cells, such as nerve
      growth factor (NGF), brain-derived neurotrophic factor (BDNF) and S-100, between
      Schwann cells cultured in the silk fibroin extraction fluid and in plain L15
      medium by the aid of immunocytochemistry, RT-PCR and Western analysis.
      Collectively, these data indicate that silk fibroin has good biocompatibility
      with DRG and is also beneficial to the survival of Schwann cells without exerting
      any significant cytotoxic effects on their phenotype or functions, thus providing
      an experimental foundation for the development of silk fibroin as a candidate
      material for nerve tissue engineering applications.

PMID- 17188748
TI  - New perspectives on the mechanisms through which nitric oxide may affect learning
      and memory processes.
AB  - Nitric oxide (NO) has been well established as a molecule necessary for memory
      consolidation. Interestingly, the majority of research has focused on only a
      single mechanism through which NO acts, namely the up-regulation of guanylate
      cyclase (GC). However, since NO and NO-derived reactive nitrogen species are
      capable of interacting with a broad array of enzymes, ion channels and receptors,
      a singular focus on GC appears short-sighted. Although NO inhibits the action of
      a number of molecules there are four, in addition to GC, which are up-regulated
      by the direct presence of NO, or NO-derived radicals, and implicated in memory
      processing. They are: cyclic nucleotide-gated channels; large conductance calcium
      activated potassium channels; ryanodine receptor calcium release (RyR) channels;
      and the enzyme mono(ADP-ribosyl) transferase. This review presents evidence that
      not only are these four molecules worthy of investigation as GC-independent
      mechanisms through which NO may act, but that behavioural evidence already exists
      suggesting a relationship between NO and the RyR channel.

PMID- 17188749
TI  - Evaluation of chemical and ecotoxicological characteristics of biodegradable
      organic residues for application to agricultural land.
AB  - The use of organic waste and compost as a source of organic matter and nutrients
      is a common practice to improve soil physico-chemical properties, meanwhile
      reducing the need for inorganic fertilisers. Official guidelines to assess sewage
      sludge and compost quality are mostly based on total metal content of these
      residues. Measurement of the total concentration of metals may be useful as a
      general index of contamination, but provides inadequate or little information
      about their bioavailability, mobility or toxicity when the organic residue is
      applied to the soil. However, ecotoxicity tests provide an integrated measure of
      bioavailability and detrimental effects of contaminants in the ecosystem. In the
      present study, three different types of biodegradable organic residues (BORs)
      have been considered: sewage sludge from municipal wastewater treatment (SS),
      compost from the organic fraction of unsorted municipal solid waste (MSWC), and
      garden waste compost (GWC). The BORs were subjected to chemical characterisation
      and total metal quantification (Cd, Cr, Cu, Ni, Pb and Zn), in order to verify
      their suitability for land application. Water leachability was determined through
      the DIN 38414-S4 method, while the modified BCR sequential extraction procedure
      was used for metal speciation. Ecotoxicity of the BORs was studied by direct and
      indirect bioassays. Direct toxicity bioassays were: plant growth tests with cress
      (Lepidium sativum L.) and barley (Hordeum vulgare L.), and earthworm (Eisenia
      fetida) mortality. On the other hand, indirect exposure bioassays, with leachate
      from the residues, took into account: luminescent bacteria (Vibrio fischeri),
      seed germination (L. sativum and H. vulgare) and Daphnia magna immobilization. As
      far as total metal concentration is concerned, with particular reference to Zn,
      SS resulted neither suitable for the use in agriculture nor compatible to be
      disposed of as an inert material into landfill, according to the Directive
      1999/31/EC. Zinc in SS was mainly present in exchangeable form (28.5%), appearing
      as highly bioavailable. As a consequence, SS exhibited either high ecotoxicity
      effects with the indirect exposure bioassays or significant mortality with the
      earthworm bioassay. Total content of metals in MSWC allowed its classification as
      "stabilised biowaste", according to 2nd draft [DG Env.A.2. Working document of
      Biological treatment of biowaste - 2nd draft. Directorate-General Environment,
      Brussels, 12th February; 2001. accessed
      in:http://europa.eu.int/comm/environment/waste/facts_en.htm, at 10/09/2002] while
      leachate, on the basis of the concentration of these contaminants, could be
      classified as "inert waste". This residue showed significant ecotoxicity effects
      with direct exposure bioassays as well as with the luminescent bacteria bioassay.
      However, it resulted less toxic than SS. Finally, GWC could be classified as a
      Class 2 compost, with no detectable toxic effects on the organisms used in the
      bioassays, except for the luminescent bacteria. In this case, an EC(50) of 73.0%
      was observed. Considering the results, the use of a battery of toxicity test in
      conjunction with chemical analysis should be suggested, in order to correctly
      assess possible environmental risks deriving from disposal or land application of
      biodegradable organic residues.

PMID- 17188751
TI  - The origin and cell lineage of microglia: new concepts.
AB  - Despite intense study, the precise origin and cell lineage of microglia, the
      resident mononuclear phagocytes of the nervous system, are still a matter for
      debate. Unlike macroglia (astrocytes and oligodendrocytes) and neurons, which are
      derived from neuroectoderm, microglial progenitors arise from peripheral
      mesodermal (myeloid) tissue. The view still commonly held is that tissue-resident
      mononuclear phagocytes (including microglia) are derived from circulating blood
      monocytes and these take up residence late in gestation and postnatally. However,
      microglial progenitors colonise the nervous system primarily during embryonic and
      fetal periods of development. Recent evidence indicates differences between the
      lineage of mononuclear phagocytes during the embryonic and fetal period from that
      in the neonate and adult-mononuclear phagocytes that take up residence within
      tissues are derived from a lineage of myeloid cells that is independent of the
      monocyte lineage. Our own findings on the development and differentiation of
      microglial progenitors, taken together with findings by other investigators, and
      in the context of the heterogeneity between myeloid differentiation in the fetus
      and in the adult, support the view that microglia are derived prenatally from
      mesodermal progenitors that are distinct from monocytes. Furthermore, microglial
      progenitors colonise the nervous system via extravascular routes initially. These
      findings challenge the concept that resident microglia in the nervous system are
      derived from circulating blood monocytes. Work is still underway to establish the
      tissue of origin and lineage of microglial progenitors in vivo. This information
      is critical not only from a developmental perspective, but significantly from a
      therapeutic viewpoint, as (i) the unique property of microglial progenitors to
      colonise the nervous system from the periphery allows these cells to be exploited
      as a biological and non-invasive means for cell therapy by delivering genes to
      the nervous system (microglial engraftment), and (ii) there are indications that
      microglial progenitors are specifically able to home to the nervous system. Use
      of microglial progenitors for therapeutic purposes becomes feasible only if the
      origin and cell lineage of these microglial progenitors are known and these cells
      can be isolated and manipulated in vitro (i.e., to express specific trophic
      factors) prior to therapeutic transfer (e.g., intravenously) in vivo. In this
      paper, we shall briefly consider the existing concepts on the origin and lineage
      of microglial progenitors and discuss new hypotheses in the light of emerging
      data that suggest clear differences between fetal and adult ontogeny of myeloid
      cells.

PMID- 17188750
TI  - Daptomycin in the treatment of vancomycin-resistant Enterococcus faecium
      bacteremia in neutropenic patients.
AB  - OBJECTIVE: Vancomycin resistant enterococcal (VRE) blood stream infection (BSI)
      in neutropenic patients is associated with poor outcome. We report our experience
      in treating VRE BSI in febrile, neutropenic patients with daptomycin, a recently
      licensed lipopeptide with bactericidal activity against VRE. PATIENTS AND
      METHODS: Patients with fever, neutropenia and VRE BSI were treated with more than
      one dose of daptomycin (either 6 mg/kg/day or 4 mg/kg/day) in an open label,
      emergency-use trial. Patients were then assessed for clinical and microbiological
      cures and survival. MIC's of isolates to daptomycin were determined. RESULTS:
      Nine febrile, neutropenic patients with VRE BSI received daptomycin. Four of 9
      courses (44%) had clinical and/or microbiologic cure. Two of the 5 who failed
      cure died within 3 days of initiation of daptomycin. Five subjects survived to 30
      days after the onset of BSI. CONCLUSIONS: Use of daptomycin in neutropenic
      patients with VRE BSI deserves further study as a treatment for VRE BSI in
      neutropenic patients.

PMID- 17188752
TI  - Role of carbon nano-materials in the analysis of biological materials by laser
      desorption/ionization-mass spectrometry.
AB  - At present, carbon nano-materials are being utilized in various procedures,
      especially in laser desorption/ionization-mass spectrometry (LDI-MS) for
      analyzing a range of analytes, which include peptides, proteins, metabolites, and
      polymers. Matrix-oriented LDI-MS techniques are very well established, with weak
      organic acids as energy-absorbing substances. Carbon materials, such as nano
      tubes and fullerenes are being successfully applied in the small-mass range,
      where routine matrices have strong background signals. In addition, the role of
      carbon nano-materials is very well established in the fractionation and
      purification fields. Modified diamond powder and surfaces are utilized in binding
      peptides and proteins from complex biological fluids and analyzed by matrix
      assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass
      spectrometry (MS). Polylysine-coated diamond is used for solid-phase extraction
      to pre-concentrate DNA oligonucleotides. Graphite is useful for desalting, pre
      concentration, and as energy-absorbing material (matrix) in
      desorption/ionization. Carbon nano-tubes in their different derivatized forms are
      used as matrix materials for the analysis of a range of analytes, such as
      carbohydrates, amino acids, peptides, proteins, and some environmental samples by
      LDI-MS. Fullerenes are modified in different ways to bind serum entities analyzed
      through MALDI/TOF-MS and are subsequently utilized in their identifications. In
      addition, the fullerenes are a promising matrix in LDI-MS, but improvements are
      needed.

PMID- 17188753
TI  - Membrane entrapped Saccharomyces cerevisiae in a biosensor-like device as a
      generic rapid method to study cellular metabolism.
AB  - We describe a new, faster and convenient method to study some metabolic
      characteristics - by the successful application of immobilized yeast cells (S.
      cerevisiae) in a microbial biosensor-like device. Microbial biosensors consist of
      microorganisms immobilized on the surface of a membrane or in a gel, in close
      contact with a transducer. Almost all works published to date have used
      biosensors for analyses in which a concentration-related property of the external
      medium is measured. A different approach is presented here; we have successfully
      used S. cerevisiae and a carbon dioxide electrode as the main components of a
      biosensor-like device, used as a proof of concept, for a system useful to
      characterize metabolic parameters of the microbial cells immobilized on a carbon
      dioxide electrode. The biosensor-like device we are presenting allows us to
      calculate Michaelis-Menten parameters related to the kinetics of transport and
      degradation of several carbohydrates (i.e., glucose, fructose, galactose, sucrose
      and xylose, with K(m(app)) of 6.0, 5.8, 0.9, 2.0, and 147 mM, respectively), and
      the study of the kinetics of expression of non-constitutive proteins related to
      the transport and degradation of galactose.

PMID- 17188754
TI  - Interferon receptor expression in multiple sclerosis patients.
AB  - To determine the gene expression of IFNAR1, IFNAR2 and MxA protein and the
      association with IFNbeta treatment response in MS patients. MS patients treated
      with IFNbeta had a significant decrease in IFNAR1 and IFNAR2 expression, and a
      significant increase in MxA compared to non-treated patients and healthy
      controls. Also, those patients who had a good response to treatment had a
      significant decrease in IFNAR1 and IFNAR2 expression compared to non-responders,
      non-treated patients and healthy controls. IFNbeta influences the expression of
      its receptors, and is greater in patients who respond to IFNbeta treatment. This
      down-regulation could be indicative of the response to IFNbeta.

PMID- 17188756
TI  - Neurodegeneration and -protection in autoimmune CNS inflammation.
AB  - Neurodegeneration in multiple sclerosis (MS) is the structural correlate of
      permanent neurological disability in patients. The histopathological features of
      neurodegeneration include destruction of axons as well as apoptotic cell death of
      neuronal cell bodies. Therapeutic efforts to control these clinically important
      aspects of MS pathology showed limited success so far. In this review article, we
      give an overview about the current knowledge concerning the molecular mechanisms
      of neurodegeneration in autoimmune inflammation that is mainly derived from
      animal models. Further, we critically discuss experimental neuroprotective
      strategies with respect to their functional relevance and differentiate between
      anti-apoptotic and axon protective treatment approaches.

PMID- 17188757
TI  - Simple and rapid detection of the porcine reproductive and respiratory syndrome
      virus from pig whole blood using filter paper.
AB  - The combination of Flinders Technology Associates filter papers (FTA cards) and
      real-time PCR was examined to establish a simple and rapid technique for the
      detection of porcine reproductive and respiratory syndrome virus (PRRSV) from
      whole pig blood. A modified live PRRS vaccine was diluted with either sterilised
      saline or pig whole blood, and the suspensions were applied onto the FTA cards.
      The real-time RT-PCR detection of PRRSV was performed directly with the samples
      applied to the FTA card without the RNA extraction step. Six whole blood samples
      from at random selected piglets in the PRRSV infected farm were also assayed in
      this study. The expected PCR product was successfully amplified from either
      saline diluted or pig whole blood diluted vaccine. The same PCR ampliocon was
      detected from all blood samples assayed in this study. This study suggested that
      the combination of an FTA card and real-time PCR is a rapid and easy technique
      for the detection of PRRSV. This technique can remarkably shorten the time
      required for PRRSV detection from whole blood and makes the procedure much
      easier.

PMID- 17188758
TI  - Rapid and efficient purification of Cowpea chlorotic mottle virus by sucrose
      cushion ultracentrifugation.
AB  - A simple, economical and efficient method for isolation of Cowpea chlorotic
      mottle virus (CCMV) particles was developed. Abundant viral particles could be
      obtained with three steps of 10 min duration each of conventional differential
      centrifugations and one sucrose cushion ultracentrifugation step of 2 h.
      Characterization of purified virus assessed by transmission electron microscopy,
      polyacrylamide gel electrophoresis (PAGE) and Western blot revealed the typical
      isometric particles of CCMV without any visible contamination or degradation. RNA
      extracted from purified CCMV particles showed all four RNA components by agarose
      gel electrophoresis. Both purified virus particles and RNA were biologically
      active and initiated successful infection upon inoculation to cowpea.

PMID- 17188755
TI  - The inflammatory response in stroke.
AB  - Recent works in the area of stroke and brain ischemia has demonstrated the
      significance of the inflammatory response accompanying necrotic brain injury.
      Acutely, this response appears to contribute to ischemic pathology, and anti
      inflammatory strategies have become popular. This chapter will discuss the
      current knowledge of the contribution of systemic and local inflammation in
      experimental stroke. It will review the role of specific cell types including
      leukocytes, endothelium, glia, microglia, the extracellular matrix and neurons.
      Intracellular inflammatory signaling pathways such as nuclear factor kappa beta
      and mitogen-activated protein kinases, and mediators produced by inflammatory
      cells such as cytokines, chemokines, reactive oxygen species and arachidonic acid
      metabolites will be reviewed as well as the potential for therapy in stroke and
      hypoxic-ischemic injury.

PMID- 17188759
TI  - A convenient immunochromatographic test strip for rapid diagnosis of yellow head
      virus infection in shrimp.
AB  - A simple yellow head virus (YHV) "strip test" was developed using monoclonal
      antibody Y19 (against the p20 structural protein) conjugated with colloidal gold
      as the detector antibody. Rabbit anti-recombinant p20 (rp20) protein antibody was
      used as a capture antibody at the test line (T) and goat anti-mouse IgG antibody
      (GAM) was used as the capture antibody at the control line (C). The ready-to-use
      strip was housed in a plastic case for convenient application and stored in the
      desiccated plastic bag. A sample volume of 100 microl of either haemolymph or
      gill or appendage homogenates in application buffer was applied to the sample
      chamber at one end of the strip and allowed to flow by chromatography through the
      nitrocellulose membrane to the other end. In test samples containing YHV, the
      virus would bind to colloidal gold conjugated monoclonal antibody and the
      resulting complex would be captured by the rabbit anti-rp20 antibody at the test
      line to give a reddish-purple band. Any unbound monoclonal antibody conjugated
      with colloidal gold moved across the test line to be captured by the GAM to form
      a band at the control line (C). In the sample without YHV or below the limit of
      detection for the kit, only the control line was demonstrated. This method was
      about 500 times less sensitive than that of one-step RT-PCR, but slightly more
      sensitive than dot blotting. Therefore, it could be used for primary screening of
      individual shrimp or pooled shrimp samples to confirm high levels of YHV
      infection or YHV disease outbreaks. This kit can be used to detect gill
      associated virus (GAV) infection as well since the monoclonal antibody used in
      this kit cross-reacted well with GAV. The beneficial features of this kit are
      that simple, convenient, and rapid results that can be obtained without the
      requirement of sophisticated tools or special skills.

PMID- 17188760
TI  - Evaluation of the efficacy of disinfectants against Puumala hantavirus by real
      time RT-PCR.
AB  - Puumala virus, a hantavirus belonging to the Bunyaviridae family, causes a human
      disease known as nephropathia epidemica, a mild form of hemorrhagic fever with
      renal syndrome. The implementation of effective decontamination procedures is
      critical in hantavirus research to minimize the risk of personnel exposure. This
      study investigated the efficacy of Clidox((R)), Dettol((R)), ethanol, Halamid
      d((R)), peracetic acid, sodium hypochloride and Virkon((R))S for inactivating
      Puumala virus. A real-time quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) was used to quantify Puumala virus before and after treatment
      with these products. Inactivation of Puumala virus was effective after 10min with
      all products except ethanol. Inactivation with absolute ethanol was effective
      only after 30min. Using the qRT-PCR method, this study has shown that the
      commercially available products Clidox((R)), Halamid-d((R)) and Virkon((R))S in
      particular represent a rapid and safe way to decontaminate surfaces with possible
      Puumala virus contamination. These products can be used in solutions of 1-2%,
      with contact times greater than 10min, for inactivating effectively Puumala
      virus.

PMID- 17188761
TI  - A matter of time: internal delays in binaural processing.
AB  - As an animal navigates its surroundings, the sounds reaching its two ears change
      in waveform similarity (interaural correlation) and in time of arrival
      (interaural time difference, ITD). Humans are exquisitely sensitive to these
      binaural cues, and it is generally agreed that this sensitivity involves
      coincidence detectors and internal delays that compensate for external acoustic
      delays (ITDs). Recent data show an unexpected relationship between the tuning of
      a neuron to frequency and to ITD, leading to several proposals for sources of
      internal delay and the neural coding of interaural temporal cues. We review the
      alternatives, and argue that an understanding of binaural mechanisms requires
      consideration of sensitivity not only to ITDs, but also to interaural
      correlation.

PMID- 17188762
TI  - Differentially expressed genes of Tetrahymena thermophila in response to
      tributyltin (TBT) identified by suppression subtractive hybridization and real
      time quantitative PCR.
AB  - Tributyltin (TBT) is widely used as antifouling paints, agriculture biocides, and
      plastic stabilizers around the world, resulting in great pollution problem in
      aquatic environments. However, it has been short of the biomonitor to detect TBT
      in freshwater. We constructed the suppression subtractive hybridization library
      of Tetrahymena thermophila exposed to TBT, and screened out 101 Expressed
      Sequence Tags whose expressions were significantly up- or down-regulated with TBT
      treatment. From this, a series of genes related to the TBT toxicity were
      discovered, such as glutathione-S-transferase gene (down-regulated), plasma
      membrane Ca2+ ATPase isoforms 3 gene (up-regulated) and NgoA (up-regulated).
      Furthermore, their expressions under different concentrations of TBT treatment
      (0.5-40 ppb) were detected by real time fluorescent quantitative PCR. The
      differentially expressed genes of T. thermophila in response to TBT were
      identified, which provide the basic to make Tetrahymena as a sensitive, rapid and
      convenient TBT biomonitor in freshwater based on rDNA inducible expression
      system.

PMID- 17188763
TI  - Genomic and proteomic expression analysis of Leishmania promastigote and
      amastigote life stages: the Leishmania genome is constitutively expressed.
AB  - Leishmania are protozoan parasites that cause a wide spectrum of clinical
      diseases in humans and are a major public health risk in several countries.
      Leishmania life cycle consists of an extracellular flagellated promastigote stage
      within the midgut of a sandfly vector, and a morphological distinct intracellular
      amastigote stage within macrophages of a mammalian host. This study reports the
      use of DNA oligonucleotide genome microarrays representing 8160 genes to analyze
      the mRNA expression profiles of L. major promastigotes and lesion derived
      amastigotes. Over 94% of the genes were expressed in both life stages. Advanced
      statistical analysis identified a surprisingly low degree of differential mRNA
      expression: 1.4% of the total genes in amastigotes and 1.5% in promastigotes.
      These microarray results demonstrate that the L. major genome is essentially
      constitutively expressed in both life stages and suggest that Leishmania is
      constitutively adapted for survival and replication in either the sandfly vector
      or macrophage host utilizing an appropriate set of genes for each vastly
      different environment. Quantitative proteomics, using the isotope coded affinity
      tag (ICAT) technology and mass spectrometry, was used to identify L. infantum
      promastigote and axenic amastigote differentially expressed proteins. Of the 91
      distinct proteins identified, 8% were differentially expressed in the amastigote
      stage, 20% were differentially expressed in the promastigote stage, and the
      remaining 72% were considered constitutively expressed. The differential
      expression was validated by the identification of previously reported stage
      specific proteins and identified several amastigote and promastigote novel stage
      specific proteins.

PMID- 17188764
TI  - Schistosoma mansoni eggs excrete specific free oligosaccharides that are
      detectable in the urine of the human host.
AB  - In infections with Schistosoma mansoni the paired adult worms produce hundreds of
      eggs daily, of which many get trapped in various organs of the human host. The
      eggs produce complex and unique protein- and lipid-linked glycans, which are
      important activators and modulators of the host's immune response. The same
      parasite-derived glycoconjugates are also attractive immunodiagnostic targets in
      enzyme-linked immunosorbent assays (ELISAs), which detect circulating antigens in
      serum or urine of the host. Here, we report for the first time that in addition
      to glycoprotein and glycolipid antigens, schistosome eggs also excrete unique
      unconjugated oligosaccharides. Employing the schistosome-specific anti
      carbohydrate monoclonal antibody 114-4D12 in an affinity purification approach, a
      specific set of free oligosaccharides was detected by matrix-assisted laser
      desorption-ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in human S.
      mansoni infection urine as well as in egg-incubation medium, but not in worm
      culture medium. Nano-scale reverse-phase liquid chromatography-mass spectrometry
      (nano-RP-LC-MS) analysis of the purified egg-derived oligosaccharides indicated
      that the captured compounds form a series of multi-fucosylated multimeric N
      acetylhexosamine chains with a non-reducing terminal Fucalpha1-2Fucalpha1
      3GalNAcbeta1-4(Fucalpha1-2Fucalpha1-3)GlcNAcbeta1- (DF-LDN-DF) sequence which
      forms the epitope of mAb 114-4D12. Since fucosylated (egg) glycoconjugates have
      been shown to harbour immunogenic properties, we anticipate that these
      unconjugated oligosaccharides also play a role in the immunobiology associated
      with schistosome eggs. Moreover, our data indicate that mass spectrometric
      detection of a set of signature molecules in urine has potential as a new
      approach for the diagnosis of schistosomiasis and possibly other helminth
      infections.

PMID- 17188766
TI  - Combined prognostic value of peak O(2) uptake and microvolt level T-wave
      alternans in patients with idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Despite the great improvement in clinical management of patients with
      idiopathic dilated cardiomyopathy (DCM), sudden cardiac death (SCD) and death due
      to worsening heart failure (HF) remain a challenging problem. The assessment of
      oxygen consumption (peakVO(2)) has been recognized as an independent marker of
      mortality. Nevertheless peakVO(2) is not helpful in the risk stratification of
      SCD. Given this limitation, the association with another non-invasive test able
      to predict SCD such as microvolt level T-wave alternans (MTWA) would be useful.
      OBJECTIVES: To determine the combined predictive value of peakVO(2) and MTWA in
      patients with DCM. METHODS: Seventy consecutive DCM patients were prospectively
      investigated. PeakVO(2) and MTWA were determined during bicycle exercise testing.
      Primary composite study end-point was defined as major cardiac events (MCE):
      total cardiac death or documented sustained VT/VF (including appropriate ICD
      shock). Secondary end-point was defined as arrhythmic events (AE): SCD or
      documented sustained VT/VF. RESULTS: Thirty-nine patients (55%) had a
      peakVO(2)<10 ml/kg/min, while 40 patients (57%) showed an abnormal MTWA test.
      During an average follow-up of 19.2+/-10.7 months, 11 MCE of which 6 AE have been
      documented. Among patients with abnormal MTWA and peakVO(2)<10 ml/kg/min 8 MCE of
      which 5 AE occurred while among patients with normal MTWA and peakVO(2)> or =10
      ml/kg/min no event occurred. From multivariate analysis, the combined prognostic
      value of MTWA and peakVO(2) achieved statistical significance for MCE (p=0.03, HR
      0.28, 95% CI 0.12-0.95) and for AE (p=0.05, HR 0.39, 95% CI 0.18-0.99) while MTWA
      alone was a significant predictor of AE (p=0.04, HR 0.32, 95% CI 0.14-0.93).
      CONCLUSIONS: Our results suggest that only the association of MTWA and peakVO(2),
      but not the two single tests, is a significant prognostic marker of both MCE and
      AE in DCM patients. However, MTWA alone confirms its predictive power as
      arrhythmic risk stratifier in this population.

PMID- 17188765
TI  - Targeted identification of a unique glycan epitope of Schistosoma mansoni egg
      antigens using a diagnostic antibody.
AB  - The eggs of Schistosoma mansoni express a plethora of glycoconjugate antigens. A
      specific subset of these antigens can be detected in the serum or urine of
      infected individuals by a diagnostic sandwich ELISA using the anti-carbohydrate
      monoclonal antibody (mAb) 114-4D12-A [Nourel Din MS, Nibbeling R, Rotmans JP,
      Polderman AM, Krijger FW, Deelder AM. Quantitative determination of circulating
      soluble egg antigen in urine and serum of Schistosoma mansoni-infected
      individuals using a combined two-site enzyme-linked immunosorbent assay. Am J
      Trop Med Hyg 1994;50:585-94]. We used affinity chromatography to isolate the 114
      4D12-binding glycoprotein subset from soluble egg antigens (SEA) of S. mansoni.
      SEA and the isolated SEA-subset (SEA-4D12) were subjected to reductive beta
      elimination and hydrazinolysis to release intact glycans and glycan fragments,
      respectively, from the protein backbones. The released glycans were characterised
      by matrix-assisted laser-desorption-ionisation time-of-flight (MALDI-TOF) mass
      spectrometry (MS), liquid-chromatography (LC)-MS and gas chromatography (GC)-MS
      linkage analysis. Glycans released by reductive beta-elimination from SEA-4D12
      were larger and more heavily fucosylated than glycans released from SEA. Most SEA
      4D12 glycans contained a branched O-glycan core structure carrying up to 4 N
      acetylhexosamines per chain which were substituted with maximum 12 fucose
      residues. Hydrazinolysis of SEA-4D12 resulted in the release of fucosylated
      antenna fragments. After 2-aminobenzamide (2AB)-labelling these fragments were
      subjected to 114-4D12-affinity purification. Normal phase (NP)-LC analysis of the
      flow-through and retained fractions indicated that the Fucalpha1-2Fucalpha1
      3GalNAcbeta1-4(Fucalpha1-2Fucalpha1-3)GlcNAcbeta1- element forms the epitope of
      mAb 114-4D12. Most O-glycans from SEA-4D12 contain this structural element.
      Epitope-bearing N-glycans have not been found. In terms of abundance in total
      SEA, only a minority of all glycans possesses the epitope. This multifucosylated
      motif has so far only been found in schistosomes, providing a structural basis
      for the high specificity of the diagnostic antibody.

PMID- 17188767
TI  - Evidence that non-lipid cardiovascular risk factors are associated with high
      prevalence of coronary artery disease in patients with heterozygous familial
      hypercholesterolemia or familial combined hyperlipidemia.
AB  - BACKGROUND: Heterozygous familial hypercholesterolemia (hFH) and familial
      combined hyperlipidemia (FCH) have been associated with increased risk for
      coronary artery disease (CAD), but the impact of traditional risk factors to the
      incidence of CAD in these patients remains unknown. The present study evaluates
      the contribution of such risk factors to the development of CAD in these two
      dyslipidemic populations. METHODS: This cross-sectional study enrolled a total
      1306 subjects; 600 individuals with hFH (mean age 41+/-13 years, 261 males and
      339 females), and 706 individuals with FCH (mean age 49+/-11 years, 463 males and
      243 females). Blood samples were collected after 12 hours fasting period, and
      serum lipids were determined. Multivariate logistic regression models were used
      to estimate the odds ratios of CAD based on the type of hyperlipidemia, after
      adjustment for demographic characteristics and risk factors. RESULTS: Subjects
      with FCH were older (P<0.001), and they had a significantly increased prevalence
      of hypertension, diabetes and metabolic syndrome (40 vs. 10%, 13 vs. 2% and 41
      vs. 6% respectively, all P<0.001) compared to the hFH group. Total cholesterol,
      LDL-cholesterol, and apolipoprotein B levels were higher (all P<0.001) in hFH
      subjects. Although in multivariate analysis lipid abnormalities found in hFH were
      associated with increased risk of CAD (P<0.001) compared with lipid abnormalities
      of FCH, the overall prevalence of CAD was similar between the two groups (16.7
      vs. 15.3%, P=NS). CONCLUSIONS: Despite the high atherogenic potential of altered
      lipid metabolism found in hFH, the prevalence of CAD is similarly increased in
      patients with hFH or FCH. This may be related to the clustering of non-lipid
      cardiovascular risk factors, such as diabetes mellitus, observed in patients with
      FCH.

PMID- 17188768
TI  - "It wasn't me, it was them!" social influence in risky behavior by adolescents.
AB  - Many years of concerted policy effort in Western countries has not prevented
      young people from experimenting with cigarettes, alcohol and marijuana. One
      potential explanation is that social interactions make consumption "sticky". We
      use detailed panel data from the Add Health survey to examine risky behavior (the
      consumption of tobacco, alcohol and marijuana) by American adolescents. We find
      that, even controlling for school fixed effects, these behaviors are correlated
      with lagged peer group behavior. Peer group effects are strongest for alcohol
      use, and young males are more influential than young females. Last, we present
      some evidence of non-linearities in social interactions.

PMID- 17188769
TI  - Reference pricing of pharmaceuticals.
AB  - We consider a therapeutic market with potentially three pharmaceutical firms. Two
      of the firms offer horizontally differentiated brand-name drugs. One of the brand
      name drugs is a new treatment under patent protection that will be introduced if
      the profits are sufficient to cover the entry costs. The other brand-name drug
      has already lost its patent and faces competition from a third firm offering a
      generic version perceived to be of lower quality. This model allows us to compare
      generic reference pricing (GRP), therapeutic reference pricing (TRP), and no
      reference pricing (NRP). We show that competition is strongest under TRP,
      resulting in the lowest drug prices (and medical expenditures). However, TRP also
      provides the lowest profits to the patent-holding firm, making entry of the new
      drug treatment least likely. Surprisingly, we find that GRP distorts drug choices
      most, exposing patients to higher health risks.

PMID- 17188770
TI  - Hybridization of genomic DNA to microarrays: a challenge for the analysis of
      environmental samples.
AB  - The use of DNA microarrays for detection and identification of bacteria and genes
      of interest from various environments (e.g. soil, sediment, water column...) is a
      major challenge for microbiologists working on functional diversity. So far, most
      of the genomic methods that have been described rely on the use of taxonomic
      markers (such as 16S rRNA) that can be easily amplified by PCR prior to
      hybridization on microarrays. However, taxonomical markers are not always
      informative on the functions present in these bacteria. Moreover, genes for which
      sequence database is limited or that lack any conserved regions will be difficult
      to amplify and thus to detect in unknown samples. Furthermore, PCR amplification
      often introduces biases that lead to inaccurate analysis of microbial
      communities. An alternative solution to overcome these strong limitations is to
      use genomic DNA (gDNA) as target for hybridisation, without prior PCR
      amplification. Though hybridization of gDNA is already used for comparative
      genome hybridization or sequencing by hybridization, yet to the high cost of
      tiling strategies and important data filtering, its adaptation for use in
      environmental research poses great challenges in terms of specificity,
      sensitivity and reproducibility of hybridization. Considering the very faint
      number of publications that have described hybridization of gDNA to microarrays
      for environmental applications, we confront in this review the different
      approaches that have been developed so far, and propose alternative strategies
      that may contribute to improve the development of microarrays for studying the
      microbial genetic structure and composition of samples of high environmental and
      ecological value.

PMID- 17188772
TI  - Mould germination: data treatment and modelling.
AB  - The objectives of this study were i/ to examine germination data sets over a
      range of environmental conditions (water activity, temperature) for eight food
      spoilage moulds, ii/ to compare the ability of the Gompertz equation and logistic
      function to fit the experimental plots, iii/ to simulate germination by assessing
      various distributions of the latent period for germination amongst a population
      of spores. Data sets (percentage germination, P (%), versus time, t) of
      Aspergillus carbonarius, Aspergillus ochraceus, Fusarium verticillioides,
      Fusarium proliferatum, Gibberella zeae, Mucor racemosus, Penicillium chrysogenum
      and Penicillium verrucosum were analysed. No correlation, or relationship between
      the mean percentage [mean (P)] and the variance [var (P)] was found. Therefore no
      transformation of the germination data was required. Experimental data were
      fitted by using the Gompertz equation P = A exp (-exp [mu(m) e/A (delta - t) +
      1]) and the logistic function P = Pmax/(1 + exp (k (tau - t))). Based on the
      residual mean square error (RMSE), no model performed better than the other one.
      However, model parameters were generally determined more precisely with the
      logistic model than with the Gompertz one. The time course of fungal spore
      germination curves was simulated assuming different distributions of the latent
      period for germination, lag, amongst a population of spores. The growth rate of
      germ tubes was calculated by means of the relationship: lag x rate = k. For
      normal Gaussian distributions, germination curves were symmetrical with respect
      to the inflection point and should be modelled with the logistic function. Skewed
      distributions were capable of simulating an asymmetric germination curve that was
      fitted by the Gompertz model. Future studies should be conducted for assessing
      whether the distributions assumed in this paper are in accordance with the
      experimental distributions that are still unknown.

PMID- 17188771
TI  - Characterisation and biochemical properties of predominant lactic acid bacteria
      from fermenting cassava for selection as starter cultures.
AB  - A total of 375 lactic acid bacteria were isolated from fermenting cassava in
      South Africa, Benin, Kenya and Germany, and were characterised by phenotypic and
      genotypic tests. These could be divided into five main groups comprising strains
      of facultatively heterofermentative rods, obligately heterofermentative rods,
      heterofermentative cocci, homofermentative cocci and obligately homofermentative
      rods, in decreasing order of predominance. Most of the facultatively
      heterofermentative rods were identified by phenotypic tests as presumptive
      Lactobacillus plantarum-group strains, which also comprised the most predominant
      bacteria (54.4% of strains) isolated in the study. The next predominant group of
      lactic acid bacteria (14.1% of total isolates) consisted of obligately
      heterofermentative rods belonging either to the genus Lactobacillus or Weissella,
      followed by the heterofermentative cocci (13.9% of isolates) belonging to the
      genera Weissella or Leuconostoc. Homofermentative cocci were also isolated (13.3%
      of isolates). Biochemical properties such as production of alpha-amylase, beta
      glucosidase, tannase, antimicrobials (presumptive bacteriocin and H(2)O(2)
      production), acidification and fermentation of the indigestible sugars raffinose
      and stachyose, were evaluated in vitro for selection of potential starter
      strains. A total of 32 strains with one or more desirable biochemical properties
      were pre-selected and identified using rep-PCR fingerprinting in combination with
      16S rRNA sequencing of representative rep-PCR cluster isolates. Of these strains,
      18 were identified as L. plantarum, four as Lactobacillus pentosus, two each as
      Leuconostoc fallax, Weissella paramesenteroides and Lactobacillus fermentum, one
      each as Leuconostoc mesenteroides subsp. mesenteroides and Weissella cibaria,
      while two remained unidentified but could be assigned to the L. plantarum-group.
      These strains were further investigated for clonal relationships, using RAPD-PCR
      with three primers, and of the 32 a total of 16 strains were finally selected for
      the development as starter cultures for Gari production.

PMID- 17188773
TI  - Genetic diversity of Listeria monocytogenes recovered from infected persons and
      pork, seafood and dairy products on retail sale in France during 2000 and 2001.
AB  - Growth of the food-borne human pathogen Listeria monocytogenes to large numbers
      in ready-to-eat food products greatly increases the risk of disease for
      susceptible consumers. A better knowledge of the population structure of L.
      monocytogenes present in retailed food could allow better prevention strategies
      to be developed. We present the analysis of 450 L. monocytogenes isolates, 179
      responsible for sporadic human cases of listeriosis and 271 isolated from foods
      collected from retailers. All isolates were investigated by multiplex PCR (food
      isolates), allowing serovar predictions, or serotyped (human isolates), and DNA
      macrorestriction patterns were determined. Isolates from different sources were
      significantly differently distributed into PCR groups. PCR group IIa,
      corresponding to serovars 1/2a and 3a, was predominant in food isolates (58%;
      OR=3.19; P<1 x 10(-7)). A larger proportion of human isolates belonged to PCR
      group IVb, corresponding to serovars 4b, 4d and 4e (44%; OR=5.69; P<1 x 10(-7)).
      DNA macrorestriction pattern analysis of PCR group IIa isolates showed that
      isolates from pork products had a very low diversity (ID=0.905) whereas isolates
      from humans were more diverse (ID=0.976). Furthermore, 78% of the pork product
      isolates belonging to PCR group IIa exhibited only two AscI profiles, a(1) and
      a(2), which were very similar (94%). DNA array analysis of representative
      isolates showed that isolates with a(1) and a(2) profiles constitute a
      homogeneous population, whereas isolates exhibiting non a(1)-a(2) profiles are
      more diverse. Six of the isolates with a(1) and a(2) profiles were selected and
      investigated for their gene content using a DNA array. With respect to 295
      strains present in our data collection, a specific pattern of the presence and
      absence of 15 genes was identified. Five are predicted to encode internalins and
      cell surface proteins, and eight of the genes were missing in this group. They
      code for cell surface proteins, transcriptional regulators, an acylase, a sugar
      phosphorylase and proteins of unknown functions. The ability of strains to
      multiply in different niches may be determined by the presence or absence of
      these genes.

PMID- 17188774
TI  - Cloning and characterization of the dxs gene, encoding 1-deoxy-d-xylulose 5
      phosphate synthase from Agrobacterium tumefaciens, and its overexpression in
      Agrobacterium tumefaciens.
AB  - A newly isolated gene dxs11 from Agrobacterium tumefaciens (KCCM 10413), an
      organism with potential for the industrial production of ubiquinone-10
      (UbiQ(10)), encoding a 1-deoxy-d-xylulose 5-phosphate synthase (Dxs), was cloned
      in Escherichia coli and its nucleotide sequence was determined. DNA sequence
      analysis revealed an open reading frame of 1920bp, capable of encoding a
      polypeptide of 640 amino acids residues with a calculated isoelectric point of pH
      5.63 and a molecular mass of 68,054Da. The homodimeric enzyme was overexpressed
      in E. coli and purified as an active soluble form. The enzyme required thiamine
      diphosphate and a divalent metal ion, either Mg(2+) or Mn(2+), for enzymatic
      activity. The enzyme had an optimal pH and temperature of 8.0 and 37 degrees C,
      respectively, with a k(cat) of 26.8s(-1) and a k(cat)/K(m) of 0.67 and 1.17s(
      1)M(-1) for pyruvate and d-glyceraldehyde 3-phosphate, respectively. A.
      tumefaciens Dxs showed a comparable catalytic efficiency to other Dxs proteins.
      The dxs11 gene was transformed into A. tumefaciens KCCM 10413, and the resulting
      recombinant, A. tumefaciens pGX11, showed higher UbiQ(10) production (502.4mg/l)
      and content (8.3mg/gDCW) than A. tumefaciens KCCM 10413, by 21.9 and 23.9%,
      respectively. This work describes Dxs from A. tumefaciens, an organism with the
      potential for industrial UbiQ(10) production, and the first metabolic engineering
      study with the non-mevalonate pathway enzyme in A. tumefaciens.

PMID- 17188775
TI  - Raf-1 and protein kinase B regulate cell survival through the activation of NF
      kappaB in hepatitis B virus X-expressing cells.
AB  - We previously demonstrated that activation of NF-kappaB by the hepatitis B virus
      X (HBx) gene plays an important role in cell survival. In the present study, we
      explored the upstream mediators of NF-kappaB activation and their correlations
      with cell survival. XTT assays and colony generation assays revealed that
      inhibition of NF-kappaB activation indeed increased cell death in HBx-expressing
      cells. Utilizing inactivating mutants of signal transducers, we showed that
      dominant negative mutants of stress-activated protein kinase/extracellular signal
      regulated kinase (SEK1) or PKCalpha significantly diminished the HBx-mediated NF
      kappaB activation. However, neither of these mutants significantly affected the
      cell survival in colony generation assays. In contrast, inactivating mutants of
      Raf-1 or PKB (protein kinase B)/Akt abrogated the HBx-mediated NF-kappaB
      activation and also suppressed the cell survival. Our results suggest that the
      Raf-1 or PKB-mediated NF-kappaB activation promotes cell survival in HBx
      expressing cells.

PMID- 17188776
TI  - A novel polymer-paclitaxel conjugate based on amphiphilic triblock copolymer.
AB  - A novel amphiphilic polymer-paclitaxel conjugate P(LGG-paclitaxel)-PEG-P(LGG
      paclitaxel) has been prepared. It was derived from its parent polymer P(LGG)-PEG
      P(LGG), poly{(lactic acid)-co-[(glycolic acid)-alt-(l-glutamic acid)]}-block
      poly(ethylene glycol)-block-poly{(lactic acid)-co-[(glycolic acid)-alt-(l
      glutamic acid)]}, which was prepared by ring-opening copolymerization of l
      lactide (LLA) with (3s)-benzoxylcarbonylethyl-morpholine-2,5-dione (BEMD) in the
      presence of dihydroxyl PEG with molecular weight of 4600 as a macroinitiator
      using stannous octoate (Sn(Oct)(2)) as catalyst, and by subsequent catalytic
      hydrogenation. It could self-assemble into micelles in an aqueous system with
      P(LGG-paclitaxel) block in the core and PEG in the shell. ESEM and DLS analysis
      of the micelles revealed a homogeneous spherical morphology and a unimodal size
      distribution. In vitro release of paclitaxel from the conjugate micelles showed
      that its release rate depended on pH value and was higher at lower pH than in
      neutral condition. In vitro antitumor activity of the paclitaxel conjugate
      against rat brain glioma C6 cells was evaluated by MTT method. The results showed
      that the paclitaxel can be released from the conjugate without losing
      cytotoxicity.

PMID- 17188777
TI  - Pegylation of liposomes favours the endosomal degradation of the delivered
      phosphodiester oligonucleotides.
AB  - Liposomal vesicles have been widely investigated as carriers for the
      intracellular delivery of oligonucleotides (ONs). To avoid unspecific uptake by
      the reticulo endothelial system, 'pegylation' of the liposomes, by incorporating
      polyethyleneglycol (PEG) at the surface, has been an attractive strategy. While
      pegylation has a clear benefit on the systemic level, one could wonder if
      pegylation also benefits the delivery efficacy of liposomes at the intracellular
      level. We compared the intracellular distribution of non-pegylated and pegylated
      liposomes, with special attention to the integrity of the oligonucleotides they
      are carrying. After uptake in the cells, the non-pegylated liposomes efficiently
      escaped from the endosomes thereby releasing phosphodiester oligonucleotides (PO
      ONs) in the cytoplasm of the cells. The PO-ONs were however rapidly degraded in
      the intracellular environment. In contrast to non-pegylated liposomes, pegylated
      liposomes failed in protecting the PO-ONs they were carrying, leading to rapid
      degradation of the PO-ONs in the endosomal compartment. Furthermore, the PEG
      chains inhibited the endosomal escape of the degraded ONs. These intracellular
      findings explain why pegylated liposomes failed in establishing an antisense
      effect.

PMID- 17188778
TI  - HOM-C evolution in Drosophila: is there a need for Hox gene clustering?
AB  - The conservation of Homeotic (Hox) gene clustering and colinearity in many
      metazoans indicates that functional constraints operate on this genome
      organization. However, several studies have questioned its relevance in
      Drosophila. Here, we analyse the genomic organization of Hox and Hox-derived
      genes in 13 fruitfly species and the mosquito Anopheles gambiae. We found that at
      least seven different Homeotic complex (HOM-C) arrangements exist among
      Drosophila species, produced by three major splits, five microinversions and six
      gene transpositions. This dynamism contrasts with the stable organization of the
      complex in many other taxa. Although there is no evidence of an absolute
      requirement for Hox gene clustering in Drosophila, we found that strong
      functional constraints act on the individual genes.

PMID- 17188779
TI  - Toxicological overview of impurities in pharmaceutical products.
AB  - While the use of pharmaceuticals is always a balance of risks and benefits, the
      same is not true for impurities in pharmaceuticals; impurities convey only risk.
      A number of international guidelines and regional guidances instruct drug
      developers and regulatory agencies on how to evaluate and control impurities in
      drug substances and drug products. While impurities should always be reduced to
      the lowest levels that are reasonably practical, it is acknowledged that
      impurities cannot be reduced to zero and specifications for impurities need to be
      established. This chapter discusses practical and theoretical methods for
      qualification of different classes of impurities.

PMID- 17188780
TI  - Results of a randomized, double-blind, vehicle-controlled efficacy trial of
      pimecrolimus cream 1% for the treatment of moderate to severe facial seborrheic
      dermatitis.
AB  - BACKGROUND: Seborrheic dermatitis is commonly treated with anti-inflammatory
      products, including topical corticosteroids. Pimecrolimus cream 1% also exerts
      anti-inflammatory activity by inhibiting T-cell cytokine production. OBJECTIVE:
      We sought to compare the efficacy and safety of twice-daily pimecrolimus for
      treatment of moderate to severe facial seborrheic dermatitis. METHODS: This
      double-blind, vehicle-controlled, 4-week trial randomized patients with
      seborrheic dermatitis to pimecrolimus or vehicle (1:1). Clinical assessments
      (erythema [0-3] and scaling [0-3] combined for a total area score [0-6]) were
      performed at weeks 0, 2, and 4. Inclusion criteria included total area score 4 or
      greater and erythema 2 or greater. The prespecified primary variable, change from
      baseline in total area score at week 4, was analyzed using a two-sample t test
      for intent-to-treat and per protocol populations. RESULTS: In all, 96 adults of
      mean age 59.6 years, 88.5% male, were randomized (n = 47 pimecrolimus; 49
      vehicle). At week 4, the mean change from baseline in total area score was 3.7
      versus 3.3 for pimecrolimus and vehicle groups, respectively (intent-to-treat: P
      = .1913; 95% confidence interval (CI) for difference [-0.195, 0.961]). Per
      protocol analysis (n = 41 pimecrolimus; 46 vehicle) indicated a significant
      difference between groups (mean change 3.9 pimecrolimus vs 3.2 vehicle; P =
      .0156; CI [0.129, 1.197]). The superiority of pimecrolimus was observed as early
      as week 2 (intent-to-treat: P = .0062; CI [0.132, 0.777]; per protocol: P =
      .0012; CI [0.410, 1.593]). No drug-related serious adverse events occurred. The
      most frequent drug-related adverse events were local, mild, and transient
      (pimecrolimus = 26%; vehicle = 12%). LIMITATIONS: Generalizability is limited by
      the elderly male study population. CONCLUSION: This study suggests that
      pimecrolimus cream 1% is an effective and well-tolerated treatment for moderate
      to severe facial seborrheic dermatitis.

PMID- 17188781
TI  - Rapidly growing collagenomas in multiple endocrine neoplasia type I.
AB  - Patients with multiple endocrine neoplasia type I (MEN-I) frequently develop skin
      lesions including collagenomas, angiofibromas, and lipomas. We report a patient
      with MEN-I who exhibited rapid growth of multiple collagenomas after pancreatic
      enucleation of a vasoactive intestinal peptide-secreting tumor (VIPoma) and
      excision of multiple pancreatic masses. Five of the collagenomas were
      protuberant, with the bulk of the lesion protruding above the skin. Histologic
      analysis of the collagenomas revealed broad collagen bundles in a haphazard
      arrangement and decreased elastic fibers. Rapid growth of protuberant
      collagenomas appears to be unusual in MEN-I, but we suggest that MEN-I be
      considered in patients with apparent eruptive collagenoma.

PMID- 17188782
TI  - Incorporation of air into a snack food reduces energy intake.
AB  - This study investigated how the air content of a familiar snack food affected
      energy intake and whether varying the method of serving the snack modified
      intake. We tested two versions of an extruded snack (cheese puffs) that were
      equal in energy density (5.7 kcal/g), but differed in energy per volume (less
      aerated snack: 1.00 kcal/ml; more-aerated snack: 0.45 kcal/ml). In a within
      subjects design, 16 women and 12 men consumed the snacks ad libitum in the
      laboratory during four afternoon sessions. A standard volume (1250 ml) of each
      snack was served once in a bowl and once in an opaque bag. Results showed
      significant differences in intake of the two snacks by energy (p=0.0003) and
      volume (p<0.0001); subjects consumed 21% less weight and energy (70+/-17 kcal) of
      the more-aerated snack than the less-aerated snack, although they consumed a 73%
      greater volume of the more-aerated snack (239+/-24 ml). These findings suggest
      that subjects responded to both the weight and volume of the snack. Despite
      differences in intake, hunger and fullness ratings did not differ across
      conditions. The serving method did not significantly affect intake. Results from
      this study indicate that incorporating air into food provides a strategy to
      reduce energy intake from energy-dense snacks.

PMID- 17188783
TI  - Argyrophilic grains: a distinct disease or an additive pathology?
AB  - BACKGROUND: Argyrophilic grains (AG) are silver-positive spindle-shaped lesions
      found at postmortem. Their significance is controversial. OBJECTIVE: To determine
      clinical correlates of AG and MRI patterns of atrophy that could allow premortem
      recognition of this pathology. METHODS: Cases with AG were identified from a
      longitudinal study of aging and dementia. Clinical features were compared between
      subjects with and without dementia. Voxel-based morphometry (VBM) was used to
      assess patterns of grey matter atrophy in subjects compared to controls. Whole
      brain volumes (WBV) were compared across groups. RESULTS: Twenty-two cases (14
      females; median age at death of 90 years; range: 70-101) with AG were identified.
      Eight of the 22 were demented. Those with dementia had higher Braak (p=0.02) and
      lower Mini-Mental State Examination (MMSE) (p=0.002). VBM demonstrated
      hippocampal atrophy in those with dementia (N=3) but no atrophy in those without
      (N=9). There was no difference in WBV between groups. CONCLUSION: AG is a feature
      of old age commonly occurring in non-demented subjects. In this age group, the
      presence of AG may reduce the threshold for dementia.

PMID- 17188785
TI  - Production of Escherichia coli heat labile toxin (LT) B subunit in soybean seed
      and analysis of its immunogenicity as an oral vaccine.
AB  - The B subunit of the heat labile toxin of enterotoxigenic Escherichia coli (LTB)
      was used as a model immunogen for production in soybean seed. LTB expression was
      directed to the endoplasmic reticulum (ER) of seed storage parenchyma cells for
      sequestration in de novo synthesized inert protein accretions derived from the
      ER. Pentameric LTB accumulated to 2.4% of the total seed protein at maturity and
      was stable in desiccated seed. LTB-soybean extracts administered orally to mice
      induced both systemic IgG and IgA, and mucosal IgA antibody responses, and was
      particularly efficacious when used in a parenteral prime-oral gavage boost
      immunization strategy. Sera from immunized mice blocked ligand binding in vitro
      and immunized mice exhibited partial protection against LT challenge. Moreover,
      soybean-expressed LTB stimulated the antibody response against a co-administered
      antigen by 500-fold. These results demonstrate the utility of soybean as an
      efficient production platform for vaccines that can be used for oral delivery.

PMID- 17188784
TI  - Improvement of the synthetic tri-peptide vaccine (S3Pvac) against porcine Taenia
      solium cysticercosis in search of a more effective, inexpensive and manageable
      vaccine.
AB  - Vaccination of pigs may curtail Taenia solium transmission by reducing the number
      of cysticerci, the precursors of adult intestinal tapeworms in humans. Several
      antigen preparations induce protection against porcine cysticercosis in
      experimental settings but only one subunit vaccine (S3Pvac) has been tested and
      proved effective in the field against naturally acquired disease. Besides
      improving of the vaccine's effectiveness, significant reductions in production
      costs and in the logistics of its administration are necessary for the
      feasibility of nationwide control programs. This review highlights the
      development of several versions of S3Pvac aimed to increase effectiveness, reduce
      costs and increase feasibility by novel delivery systems and alternative routes
      of administration.

PMID- 17188786
TI  - Effects of mercury on visible/near-infrared reflectance spectra of mustard
      spinach plants (Brassica rapa P.).
AB  - Mustard spinach plants were grown in mercury-spiked and contaminated soils
      collected in the field under controlled laboratory conditions over a full growth
      cycle to test if vegetation grown in these soils has discernible characteristics
      in visible/near-infrared (VNIR) spectra. Foliar Hg concentrations (0.174
      3.993ppm) of the Mustard spinach plants were positively correlated with Hg
      concentration of soils and varied throughout the growing season. Equations
      relating foliar Hg concentration to spectral reflectance, its first derivative,
      and selected vegetation indices were generated using stepwise multiple linear
      regression. Significant correlations are found for limited wavelengths for
      specific treatments and dates. Ratio Vegetation Index (RVI) and Red Edge Position
      (REP) values of plants in Hg-spiked and field-contaminated soils are
      significantly lower relative to control plants during the early and middle
      portions of the growth cycle which may be related to lower chlorophyll abundance
      or functioning in Hg-contaminated plants.

PMID- 17188787
TI  - Course and predictors of mental health of unaccompanied refugee minors in the
      Netherlands: one year follow-up.
AB  - This epidemiological investigation addresses the prevalence, course, and
      predictors of the psychological distress and behavioral problems of unaccompanied
      refugee minors living in the Netherlands. The legal guardians, teachers and
      minors themselves all reported on the mental health of the refugee minors (n=582)
      at baseline and follow-up approximately 12 months later. The self-reported
      psychological distress of refugee minors was found to be severe (50%) and of a
      chronic nature (stable for one year) which was confirmed by reports from the
      guardians (33%) and teachers (36%). The number of self-reported experienced
      adverse life events were strongly related to the severity of psychological
      distress. Baseline psychopathology was the largest predictor of psychological
      distress at follow-up reported by all informants accounting for 22-51% of the
      variance. The present study, which used a population-based sample, further
      enlarges the knowledge of mental health among refugee adolescents. The
      investigation is unique because of the large sample size, the longitudinal nature
      of the study, the use of multiple informants, and the culturally diverse sample.

PMID- 17188788
TI  - Off the couch and on the move: global public health and the medicalisation of
      nature.
AB  - In May 2004 the World Health Organization (WHO) officially launched the 'Global
      Strategy on Diet, Physical Activity and Health'. Lying at its heart is the
      recognition that many of the risk factors associated with non-communicable
      diseases, particularly poor diet and physical inactivity, have begun to move
      beyond the confines of the West. It was this apparent shift in the
      epidemiological boundaries of such diseases, along with fears over the so-called
      'double burden' that they presented to some nations, that finally prompted the
      WHO to develop such a far reaching strategy. This paper adds to the on-going
      debate surrounding this important issue by drawing on the concepts of
      medicalisation, governmentality and the spatiality of scientific knowledge to
      explore one particular element of it: namely, the identification of nature as a
      setting for the promotion of physical activity. We adopt this perspective because
      we are concerned to understand the ways in which the knowledge and practice of
      the 'new' public health travels. As our analysis reveals, in many Western nations
      the natural environment has emerged as an important 'transactional zone' where
      the governmental imperative for the production of fit and active bodies coalesces
      with the individual desire to be healthy. However, while it is apparent that this
      physical activity discourse increasingly operates throughout the globe, there is
      less evidence of an equivalent discourse that promotes the health-related
      benefits of nature. We argue that this is significant because it helps us to
      recognise that contemporary public health discourse has a distinct geography.

PMID- 17188789
TI  - Facial expressivity during the clinical interview as a predictor functional
      disability in schizophrenia. a pilot study.
AB  - Despite the central role of nonverbal behavior in regulating social interactions,
      its relationship to functional disability in schizophrenia has received little
      empirical attention. This study aimed at assessing the relationship of patients'
      spontaneous facial expressivity during the clinical interview to clinician-rated
      and self-reported measures of functional disability. The nonverbal behavior of 28
      stabilized patients with schizophrenia was analyzed by using the Ethological
      Coding System for Interviews (ECSI). Functional disability was assessed using the
      Global Assessment of Functioning (GAF) scale and the Sheehan Disability Scale
      (DISS). Partial correlation analysis controlling for the confounding effects of
      neuroleptic treatment showed that facial expressivity was correlated with the GAF
      score (r=0.42, P=0.03) and the scores on the subscales of the DISS measuring work
      (r=-0.52, P=0.005) and social (r=-0.50, P=0.007) disability. In a multiple
      regression model, nonverbal behavior explained variation in patients' work and
      social disability better than negative symptoms. The results of this pilot study
      suggest that deficits in encoding affiliative signals may play a role in
      determining or aggravating functional disability in schizophrenia. One clinical
      implication of this finding is that remediation training programs designed to
      improve nonverbal communication could also serve as a useful adjunct for
      improving work and social functioning in patients with schizophrenia.

PMID- 17188790
TI  - Noradrenergic facilitation of shock-probe defensive burying in lateral septum of
      rats, and modulation by chronic treatment with desipramine.
AB  - We have previously shown that acute stress-induced release of norepinephrine (NE)
      facilitates anxiety-like behavioral responses to stress, such as reduction in
      open-arm exploration on the elevated-plus maze and in social behavior on the
      social interaction test. Since these responses represent inhibition of ongoing
      behavior, it is important to also address whether NE facilitates a response that
      represents an activation of behavior. Correspondingly, it is unknown how a
      chronic elevation in tonic steady-state noradrenergic (NA) neurotransmission
      induced by NE reuptake blockade might alter this acute modulatory function, a
      regulatory process that may be pertinent to the anxiolytic effects of NE reuptake
      blockers such as desipramine (DMI). Therefore, in this study, we investigated
      noradrenergic modulation of the shock-probe defensive burying response in the
      lateral septum (LS). In experiment 1, shock-probe exposure induced an acute 3
      fold increase in NE levels measured in LS of male Sprague-Dawley rats by
      microdialysis. Shock-probe exposure also induced a modest rise in plasma ACTH,
      taken as an indicator of perceived stress, that returned to baseline more rapidly
      in rats that were allowed to bury the probe compared to rats prevented from
      burying by providing them with minimal bedding, indicating that the active
      defensive burying behavior is an effective coping strategy that reduces the
      impact of acute shock probe-induced stress. In experiment 2, blockade of either
      alpha(1)- or beta-adrenergic receptors in LS by local antagonist microinjection
      immediately before testing reduced defensive burying and increased immobility. In
      the next experiment, chronic DMI treatment increased basal extracellular NE
      levels in LS, and attenuated the acute shock probe-induced increase in NE release
      in LS relative to baseline. Chronic DMI treatment decreased shock-probe defensive
      burying behavior in a time-dependent manner, apparent only after 2 weeks or more
      of drug treatment. Moreover, rats treated chronically with DMI showed no
      significant rise of plasma ACTH in response to shock-probe exposure. Thus, acute
      stress-induced release of NE in LS facilitated defensive burying, an active,
      adaptive behavioral coping response. Chronic treatment with the NE reuptake
      blocker and antidepressant drug DMI attenuated acute noradrenergic facilitation
      of the active burying response, and also attenuated the level of perceived stress
      driving that response. These results suggest that long-term regulation of the
      acute modulatory function of NE by chronic treatment with reuptake blockers may
      contribute to the mechanisms by which such drugs exert their anxiolytic effects
      in the treatment of stress-related psychiatric conditions, including depression
      and anxiety.

PMID- 17188791
TI  - Schizophrenia with prominent catatonic features ('catatonic schizophrenia'). II.
      Factor analysis of the catatonic syndrome.
AB  - Previous factor analyses of catatonia have yielded conflicting results for
      several reasons including small and/or diagnostically heterogeneous samples and
      incomparability or lack of standardized assessment. This study examined the
      factor structure of catatonia in a large, diagnostically homogenous sample of
      patients with chronic schizophrenia using standardized rating instruments. A
      random sample of 225 Chinese inpatients diagnosed with schizophrenia according to
      DSM-IV criteria were selected from the long-stay wards of a psychiatric hospital.
      They were assessed with a battery of rating scales measuring psychopathology,
      extrapyramidal motor status, and level of functioning. Catatonia was rated using
      the Bush-Francis Catatonia Rating Scale. Factor analysis using principal
      component analysis and Varimax rotation with Kaiser normalization was performed.
      Four factors were identified with Eigenvalues of 3.27, 2.58, 2.28 and 1.88. The
      percentage of variance explained by each of the four factors was 15.9%, 12.0%,
      11.8% and 10.2% respectively, and together they explained 49.9% of the total
      variance. Factor 1 loaded on "negative/withdrawn" phenomena, Factor 2 on
      "automatic" phenomena, Factor 3 on "repetitive/echo" phenomena and Factor 4 on
      "agitated/resistive" phenomena. In multivariate linear regression analysis
      negative symptoms and akinesia were associated with 'negative' catatonic
      symptoms, antipsychotic doses and atypical antipsychotics with 'automatic'
      symptoms, length of current admission, severity of psychopathology and younger
      age at onset with 'repetitive' symptoms and age, poor functioning and severity of
      psychopathology with 'agitated' catatonic symptom scores. The results support
      recent findings that four main factors underlie catatonic signs/symptoms in
      chronic schizophrenia.

PMID- 17188793
TI  - Stoichiometric and catalytic scavengers as protection against nerve agent
      toxicity: a mini review.
AB  - Currently fielded treatments for nerve agent intoxication promote survival, but
      do not afford complete protection against either nerve agent-induced motor and
      cognitive deficits or neuronal pathology. The use of human plasma-derived
      butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents
      in vivo has been shown to both aid survival and protect against decreased
      cognitive function after nerve agent exposure. Recently, a commercially produced
      recombinant form of human butyrylcholinesterase (r-HuBuChE; PharmAthene Inc.)
      expressed in the milk of transgenic goats has become available. This material is
      biochemically similar to plasma-derived HuBuChE in in vitro assays. The
      pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form
      of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable
      with a half-life (t(1/2)) and pharmacokinetic profile that resembled that of
      plasma-derived huBuChE. Guinea pigs were injected with 140mg/kg (i.m.) of
      pegylated r-HuBuChE 18h prior to exposure (sc) to 5.5xLD(50) VX or soman. VX and
      soman were administered in a series of three injections of 1.5xLD(50),
      2.0xLD(50), and 2.0xLD(50), respectively, with injections separated by 2h.
      Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple
      lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent
      toxicity following exposure. Assessments of motor activity, coordination, and
      acquisition of spatial memory were performed for 2 weeks following nerve agent
      exposure. There were no measurable decreases in motor or cognitive function
      during this period. In contrast, animals receiving 1.5xLD(50) challenges of soman
      or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50
      and 100% survival, respectively, but exhibited marked decrements in motor
      function and, in the case of GD, impaired spatial memory acquisition. The
      advances in this field have resulted in the decision to select both the plasma
      derived and the recombinant form of BuChE for advanced development and transition
      to clinical trials. Efforts have now been expanded to identify a catalytic
      protein capable of not only binding, but also rapidly hydrolyzing the standard
      threat nerve agents. Recent work has focused on paraoxonase-1 (PON1), a naturally
      occurring human serum enzyme with the capacity to catalyze the hydrolysis of
      nerve agents, albeit too slowly to afford dramatic protection. Using rational
      design, several amino acids involved in substrate binding have been identified
      and site-directed mutations have revealed that residue H115 plays an important
      role in binding. In addition, the stereospecificity of PON1 for the catalytic
      hydrolysis of soman has been examined. The enzyme exhibits a slight
      stereospecificity for the C+P+ isomer of soman, which is due more to preferential
      binding than to selective hydrolysis of this isomer. The results suggest that it
      may be possible to engineer a mutant form of PON1 with enhanced activity and
      stereospecificity for the most toxic nerve agent isoforms.

PMID- 17188792
TI  - Role of NAD(P)H:quinone oxidoreductase 1 in clofibrate-mediated hepatoprotection
      from acetaminophen.
AB  - Mice pretreated with the peroxisome proliferator clofibrate (CFB) are resistant
      to acetaminophen (APAP) hepatotoxicity. Whereas the mechanism of protection is
      not entirely known, CFB decreases protein adducts formed by the reactive
      metabolite of APAP, N-acetyl-p-benzoquinone imine (NAPQI). NAD(P)H:quinone
      oxidoreductase 1 (NQO1) is an enzyme with antioxidant properties that is
      responsible for the reduction of cellular quinones. We hypothesized that CFB
      increases NQO1 activity, which in turn enhances the conversion of NAPQI back to
      the parent APAP. This could explain the decreases in APAP covalent binding and
      glutathione depletion produced by CFB without affecting APAP bioactivation to
      NAPQI. Administration of CFB (500mg/kg, i.p.) to male CD-1 mice for 5 or 10 days
      increased NQO1 protein and activity levels. To evaluate the capacity of NQO1 to
      reduce NAPQI back to APAP, we utilized a microsomal activating system. Cytochrome
      P450 enzymes present in microsomes bioactivate APAP to NAPQI, which binds the
      electrophile trapping agent, N-acetyl cysteine (NAC). We analyzed the formation
      of APAP-NAC metabolite in the presence of human recombinant NQO1. Results
      indicate that NQO1 is capable of reducing NAPQI. The capacity of NQO1 to
      amelioriate APAP toxicity was then evaluated in primary hepatocytes. Primary
      hepatocytes isolated from mice dosed with CFB are resistant to APAP toxicity.
      These hepatocytes were also exposed to ES936, a high affinity, and irreversible
      inhibitor of NQO1 in the presence of APAP. Concentrations of ES936 that resulted
      in over 94% inhibition of NQO1 activity did not increase the susceptibility of
      hepatocytes from CFB treated mice to APAP. Whereas NQO1 is mechanistically
      capable of reducing NAPQI, CFB-mediated hepatoprotection does not appear to be
      dependent upon enhanced expression of NQO1.

PMID- 17188794
TI  - Reduced diversity of the human erythrocyte membrane sialic acids in polycythemia
      vera. Absence of N-glycolylneuraminic acid and characterisation of N
      acetylneuraminic acid 1,7 lactone.
AB  - Sialic acids from the erythrocyte (RBC) membrane of a patient suffering from
      polycythemia vera, a malignant orphan disorder of hematopoietic cells, was
      studied using GC/MS. We found that the sialic acid diversity of these membranes
      was drastically reduced since only four entities were identified: Neu5Ac (91.5%)
      and its 1,7 lactone Neu5Ac1,7L (7.5%) which is absent in normal RBC, Neu4,5Ac(2)
      (0.50%) and Neu4,5Ac(2) 9Lt (0.50%); in normal RBC, Neu5,7Ac(2), Neu5,9Ac(2),
      Neu5Ac9Lt, Neu5Ac8S and Neu, as well as traces of Kdn, were also present. Neu5Gc
      and its O-alkylated or O-acetylated derivatives, which are considered by various
      authors as cancer markers, were not detected.

PMID- 17188795
TI  - Mitochondrial trafficking and morphology in healthy and injured neurons.
AB  - Mitochondria are the primary generators of ATP and are important regulators of
      intracellular calcium homeostasis. These organelles are dynamically transported
      along lengthy neuronal processes, presumably for appropriate distribution to
      cellular regions of high metabolic demand and elevated intracellular calcium,
      such as synapses. The removal of damaged mitochondria that produce harmful
      reactive oxygen species and promote apoptosis is also thought to be mediated by
      transport of mitochondria to autophagosomes. Mitochondrial trafficking is
      therefore important for maintaining neuronal and mitochondrial health while
      cessation of movement may lead to neuronal and mitochondrial dysfunction.
      Mitochondrial morphology is also dynamic and is remodeled during neuronal injury
      and disease. Recent studies reveal different manifestations and mechanisms of
      impaired mitochondrial movement and altered morphology in injured neurons. These
      are likely to cause varied courses toward neuronal degeneration and death. The
      goal of this review is to provide an appreciation of the full range of
      mitochondrial function, morphology and trafficking, and the critical role these
      parameters play in neuronal physiology and pathophysiology.

PMID- 17188796
TI  - N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington's
      disease.
AB  - Many lines of evidence support a role for neuronal damage arising as a result of
      excessive activation of glutamate receptors by excitatory amino acids in the
      pathogenesis of Huntington disease. The N-methyl-d-aspartate subclass of
      ionotropic glutamate receptors (NMDARs) is more selective and effective than the
      other subclasses in mediating this damage. As well, neurons expressing high
      levels of NMDARs are lost early from the striatum of individuals affected with
      Huntington's disease (HD), and injection of NMDAR agonists into the striatum of
      rodents or non-human primates recapitulates the pattern of neuronal damage
      observed in HD. Altered NMDAR function has been reported in corticostriatal
      synapses in one mouse model of HD, and NMDAR-mediated current and/or toxicity
      have been found to be potentiated in striatal neurons from several HD mouse
      models as well as heterologous cells expressing the mutant huntingtin protein.
      Changes in NMDAR activity have been correlated with altered calcium homeostasis,
      mitochondrial membrane depolarization and caspase activation. NMDAR stimulation
      is also closely linked to mitochondrial activity, as treatment with mitochondrial
      toxins has been demonstrated to produce striatal damage that can be reversed by
      the addition of NMDAR antagonists. Recent efforts have focused on the elucidation
      of molecular pathways linking huntingtin to NMDARs, as well as the mechanisms
      which underlie the enhancement of NMDAR activity by mutant huntingtin. Here, we
      review the literature to date and recent findings concerning the role of NMDARs
      in HD pathogenesis.

PMID- 17188797
TI  - Primitive neuroectodermal tumor of the breast.

PMID- 17188798
TI  - Evaluation of the economic and environmental impact of converting cropland to
      forest: a case study in Dunhua county, China.
AB  - The Sloping Land Conversion Program (also known as "Grain for Green" or the
      Upland Conversion Program) for converting cropland to forest is one of China's
      most ambitious environmental initiatives, and is one of the world's largest land
      conservation programs with a budget of RMB 337 billion (over US$ 40 billion).
      Although environmental impacts have played a vital role in the general reasoning
      and argumentation for forest plantations, environmental impact analyses have
      often received less attention than economic analyses in the planning of
      plantation forestry projects. The overall goal of this paper is to evaluate the
      program's environmental impact considering the farmer's interests and the
      potential social benefits due to carbon sequestration in different scenarios
      based on household and field survey data in Dunhua County. Our findings are that:
      (1) in many cases, the program did not give adequate consideration to land
      productivity and environmental heterogeneity when selecting plots; (2) more than
      half of the reforestation plots were on flat cropland (slopes of less than 5
      degrees ); (3) in five of the eight townships, net incomes on reforested land
      were substantially above or below previous crop incomes, raising questions about
      the efficiency of the allocation of compensation to farmers participating in the
      program; (4) the potential carbon co-benefit increased the NPV of the program by
      5954-7009 RMB/ha. In conclusion, we recommend that more attention should be paid
      to the quality of reforestation programs rather than just their scale and note
      that consideration of potential carbon sequestration co-benefits enhances the
      benefits of cropland conversion programs.

PMID- 17188799
TI  - Vasodilation of epicardial coronary artery can be measured with transthoracic
      echocardiography.
AB  - Transthoracic Doppler echocardiography (TTE) has been introduced as a noninvasive
      tool to measure coronary flow velocity reserve (CFVR). Velocity measurement,
      however, fails to take into account epicardial coronary artery vasodilation
      during hyperemia and this may cause underestimation of CFVR measurements.
      Therefore, we sought to determine whether the vasodilation of epicardial coronary
      artery can be measured during cold pressor test (CPT) and adenosine infusion
      simultaneously with the flow velocity measurement using TTE. We studied 41
      healthy nonsmoking men with a linear high-frequency 8.0-MHz transducer. The CPT
      and adenosine infusion dilated the diameter of the distal left anterior
      descending coronary artery (LAD) from 1.4 +/- 0.4 mm to 1.5 +/- 0.4 mm (14 +/-
      13%, p < 0.01) and from 1.4 +/- 0.4 mm to 1.8 +/- 0.5 mm (31 +/- 19%, p < 0.01),
      respectively. The CPT increased flow velocity and calculated coronary blood flow
      rate (velocity time integral x cross-sectional area) from 0.23 +/- 0.05 m/s to
      0.36 +/- 0.13 m/s (31 +/- 34%, p < 0.01) and from 8.1 +/- 4.2 mL/min to 11.4 +/-
      6.0 mL/min (47 +/- 51%, p < 0.01). CFVR and calculated coronary blood flow rate
      reserve were 3.9 +/- 1.0 and 6.0 +/- 1.9, respectively. In Bland-Altman analysis,
      velocity measurements underestimated the vasodilation response of the CPT and
      adenosine compared with the measurements where epicardial diameter dilation was
      taken into account. Intra- and interobserver variability of diameter measurements
      was low (coefficient of variation [CV] 2.6 to 6.5%). Day-to-day, within-day and
      intersonographer variabilities were of similar magnitude (CV 4.6 to 8.2%),
      suggesting good reproducibility. This study demonstrates that TTE can be used to
      assess changes in both epicardial coronary artery diameter and flow velocity
      simultaneously in the distal LAD artery.

PMID- 17188800
TI  - Imaging kidney in conscious rats with high-frequency ultrasound and detection of
      two cases of unilateral congenital hydronephrosis.
AB  - A quick noninvasive screen of laboratory animal organ phenotype by high
      resolution ultrasound is useful in biomedical research and new drug discovery.
      During new drug testing, imaging animal at the conscious state avoiding
      anaesthesia does not only speed up the screening process, but also avoids the
      potential compounding interaction of anaesthetic agents with the new drugs. The
      feasibility of imaging kidney in conscious rats with high-frequency ultrasound
      was explored in this study. Two operators were involved with the procedure, with
      one operator holding the rat and the other operator doing the imaging process. A
      VisualSonics ultrasound system was used, with a 30 MHz central frequency probe at
      the resolution of 115 x 55 microm. It was feasible to hold the conscious rats
      still, allowing ultrasound imaging of kidneys, without causing stress to the
      animals. In a group of 12 male Han Wistar rats (Charles River, UK), two cases of
      unilateral congenital hydronephrosis of the right kidney were identified. The
      right kidneys with hydronephrosis showed an echolucent dilated pelvis and overall
      parenchymal hypotrophy.

PMID- 17188801
TI  - Risk-adjusted analysis of positive surgical margins following laparoscopic and
      retropubic radical prostatectomy.
AB  - OBJECTIVES: To prospectively compare in a contemporary and contemporaneous series
      the positive surgical margin (PSM) rate between laparoscopic (LRP) and retropubic
      (RRP) radical prostatectomy at the same institution. METHODS: Between 1 January
      2003 and 30 June 2005, 1177 consecutive men with clinically localized
      adenocarcinoma of the prostate underwent radical prostatectomy at the same
      institution: 485 laparoscopically and 692 through a retropubic approach. Partin
      table probability of organ-confined (OC) disease was used as an index of disease
      aggressiveness: The PSM rate between the two approaches was compared, with
      adjustment for the OC probability. RESULTS: Overall both surgical approaches had
      a comparable PSM rate of 11.3% after LRP and 11% after RRP. In a logistic
      regression analysis adjusting for OC probability, there was no statistically
      significant difference between LRP and RRP (odds ratio [OR]: 1.156; 95%
      confidence interval [%95 CI], 0.792, 1.686; p=0.5). There was a statistically
      significant decrease over time in the rate of PSM for LRP (OR: 0.71 per 100
      patients treated; %95 CI, 0.57, 0.89; p=0.003), while that of RRP was unchanged
      (OR: 1.06 per 100 patients treated; %95 CI, 0.94, 1.21; p=0.3; p=0.002 for
      interaction between change over time and procedure). CONCLUSIONS: In our
      institution, laparoscopic and retropubic radical prostatectomy provide comparable
      PSM rates for patients with clinically localized prostate cancer. The PSM rate
      over the study period remained unchanged in the RRP experience, indicating a
      mature and well-established operative technique, while that of LRP underwent a
      significant decrease, demonstrating that the procedure and therefore the results
      continued to evolve during the study.

PMID- 17188802
TI  - The stepping motor protein as a feedback control ratchet.
AB  - It is explained how going from a one headed motor protein to a stepping two
      headed motor protein is equivalent to going from a stochastically flashing
      ratchet to a feedback control ratchet. Both these ratchets have been well studied
      in the literature and their speeds and efficiencies are briefly reviewed. Next it
      is shown how a feedback control ratchet mechanism model can account for very
      accurate recent data obtained on kinesin. Finally, the role of internal friction
      in the operation of stepping motor proteins is discussed.

PMID- 17188803
TI  - Phenotypic complexity and local variations in neutral degree.
AB  - Neutrality is important in natural, molecular and artificial evolution. This work
      studies how local neutral degree varies over the genospace in a simple class of
      Lindenmayer-systems, and investigates whether this variation relates to Lempel
      Ziv complexity of the phenotype.

PMID- 17188804
TI  - Robot control with biological cells.
AB  - At present there exists a large gap in size, performance, adaptability and
      robustness between natural and artificial information processors for performing
      coherent perception-action tasks under real-time constraints. Even the simplest
      organisms have an enviable capability of coping with an unknown dynamic
      environment. Robots, in contrast, are still clumsy if confronted with such
      complexity. This paper presents a bio-hybrid architecture developed for exploring
      an alternate approach to the control of autonomous robots. Circuits prepared from
      amoeboid plasmodia of the slime mold Physarum polycephalum are interfaced with an
      omnidirectional hexapod robot. Sensory signals from the macro-physical
      environment of the robot are transduced to cellular scale and processed using the
      unique micro-physical features of intracellular information processing.
      Conversely, the response form the cellular computation is amplified to yield a
      macroscopic output action in the environment mediated through the robot's
      actuators.

PMID- 17188805
TI  - Algorithmic and complexity results for decompositions of biological networks into
      monotone subsystems.
AB  - A useful approach to the mathematical analysis of large-scale biological networks
      is based upon their decompositions into monotone dynamical systems. This paper
      deals with two computational problems associated to finding decompositions which
      are optimal in an appropriate sense. In graph-theoretic language, the problems
      can be recast in terms of maximal sign-consistent subgraphs. The theoretical
      results include polynomial-time approximation algorithms as well as constant
      ratio inapproximability results. One of the algorithms, which has a worst-case
      guarantee of 87.9% from optimality, is based on the semidefinite programming
      relaxation approach of Goemans-Williamson [Goemans, M., Williamson, D., 1995.
      Improved approximation algorithms for maximum cut and satisfiability problems
      using semidefinite programming. J. ACM 42 (6), 1115-1145]. The algorithm was
      implemented and tested on a Drosophila segmentation network and an Epidermal
      Growth Factor Receptor pathway model, and it was found to perform close to
      optimally.

PMID- 17188806
TI  - A Markovian engine for a biological energy transducer: the catalytic wheel.
AB  - The molecular machines in biological cells are made of proteins, DNAs and other
      classes of molecules. The structures of these molecules are characteristically
      "soft", highly flexible, and yet their interactions with other molecules or ions
      are specific and selective. This chapter discusses a prevalent form, the
      catalytic wheel, or the energy transducer of cells, examines its mechanism of
      action, and extracts from it a set of simple but general rules for understanding
      the energetics of the biomolecular devices. These rules should also benefit
      design of manmade nanometer scale machines such as rotary motors or track-guided
      linear transporters. We will focus on an electric work that, by matching system
      dynamics and then enhancing the conformational fluctuation of one or several
      driver proteins, converts stochastic input of energy into rotation or locomotion
      of a receptor protein. The spatial (or barrier) and temporal symmetry breakings
      required for selected driver/receptor combinations are examined. This electric
      ratchet consists of a core engine that follows the Markovian dynamic, alleviates
      difficulties encountered in rigid mechanical model, and tailors to the soft
      matter characteristics of the biomolecules.

PMID- 17188807
TI  - Boolean networks with biologically relevant rules show ordered behavior.
AB  - It was found recently that natural gene regulatory systems are governed by
      hierarchically canalyzing functions (HCFs), a special subclass of Boolean
      functions. Here we study the HCF class in detail. We present a new minimal
      logical expression for all HCFs. Based on this formula, we calculate the
      cardinality of the HCF class. Moreover, we define HCF subclasses and calculate
      their cardinality as well. Using the well-known critical connectivity condition
      2K(c)p(1-p)=1, we discuss order-chaos transitions of Boolean networks (BNs)
      regulated by functions of given HCF subclasses. Finally, analysing real gene
      regulatory rules we show that nearly all of the biologically relevant functions
      belong to the simplest HCF subclasses. This restriction is important for reverse
      engineering of transcription regulatory networks and for ensemble approach
      studies in systems biology. It is shown that Boolean networks with functions
      belonging to the biologically realized HCF subclasses show ordered behavior.

PMID- 17188808
TI  - Relationship between dilemma occurrence and the existence of a weakly dominant
      strategy in a two-player symmetric game.
AB  - Defining the dilemma game by the proposition, A game cannot sustain an increase
      of cooperation strategy in its strategy distribution, we deduced that the
      substance of a dilemma can be expressed by a productive summation of the static
      factor and the dynamic factor independently. A static factor is an element of the
      game's structure that influences a possible dilemma, which relates to a game's
      structural deviation from a situation where the cooperation strategy can be
      weakly dominant over other strategies. In contrast, a dynamic factor refers to a
      strategy distribution's influence on the dilemma by affecting the game dynamics.
      In a 2x2 game, the existence of a dilemma can be determined only by a static
      factor. That is, whether or not a dilemma occurs is related only to the
      structural effect of the game. On the other hand, in a more-than-two-strategies
      game, both static and dynamic factors determine the occurrence of a dilemma, and
      the static factor cannot solely explain the occurrence of a dilemma.

PMID- 17188809
TI  - Simple, selective and sensitive spectrophotometric determination of fenitrothion
      using novel chromogenic reagent.
AB  - A facile, rapid and sensitive spectrophotometric method was developed for the
      determination of fenitrothion in its formulations, water, food grain and
      agriculture soil samples with newly synthesised reagent. The method was based on
      the alkaline hydrolysis of fenitrothion pesticide and resultant hydrolysed
      product of fenitrothion was coupled with diazotised 4,4'-methylene-bis-(p-amino
      3'-hydroxybenzanilide) in basic medium to give orange coloured product having
      lambdamax 480 nm. The formation of coloured derivatives with the coupling agent
      is instantaneous and stable for 48 h. Beer's law was obeyed in the concentration
      range of 0.1-19.0 microg ml(-1). The proposed method is sensitive, easy to
      operate and permitted the determination of fenitrothion with a detection limits
      of 0.085 microg ml(-1). The experimental results indicate that the procedure can
      eliminate the fundamental interferences caused by other pesticides and non-target
      ions, which made these methods more sensitive and selective. The method was
      applicable to the determination of fenitrothion residue in water, food grain and
      soil samples up to ng level.

PMID- 17188810
TI  - Chromium(VI) biosorption by dried Rhizopus arrhizus: effect of salt (NaCl)
      concentration on equilibrium and kinetic parameters.
AB  - Some industrial wastewaters contain high quantities of salts besides heavy metal
      ions. The presence of salt ions leads to high ionic strength, which may
      significantly affect the performance of the biosorption process so the effect of
      salts on the biosorption of heavy metal ions should be investigated. In this
      study the biosorption of chromium(VI) from saline solutions on dried Rhizopus
      arrhizus was studied as a function of pH, initial chromium(VI) and salt (NaCl)
      concentrations in a batch system. The biosorption capacity of R. arrhizus
      strongly depended on solution pH and maximum chromium(VI) sorption capacity of
      sorbent was obtained at pH 2.0 both in the absence and in the presence of
      increasing concentrations of salt. Chromium(VI)-salt biosorption studies were
      performed at this pH value. Equilibrium uptakes of chromium(VI) increased with
      increasing chromium(VI) concentration up to 250mgl(-1) and decreased considerably
      by the presence of increasing concentrations of salt. At 100mgl(-1), initial
      chromium(VI) concentration, dried R. arrhizus biosorbed 78.0mgg(-1) of
      chromium(VI) in 72h without salt medium. When salt concentration was raised to
      50gl(-1), this value dropped to 64.0mgg(-1) of chromium(VI) at the same
      conditions resulting in 17.9% decrease of biosorption capacity. The equilibrium
      sorption data were analysed by using Freundlich, Langmuir, Redlich-Peterson and
      Langmuir-Freundlich (Sips), the two and three parameters adsorption models, using
      non-linear regression technique and isotherm constants were evaluated depending
      on salt concentration. The Langmuir-Freundlich (Sips) was the best suitable
      adsorption model for describing the biosorption of chromium(VI) individually and
      in salt-containing medium. Pseudo-first-order, pseudo-second-order and saturation
      type kinetic models described the biosorption kinetics accurately at all
      chromium(VI) concentrations in the absence and in the presence of changing
      concentrations of salt. Isotherm and saturation type kinetic constants varied due
      to the level of salt were expressed as a function of initial salt concentration.

PMID- 17188811
TI  - Performance characteristics of the limulus amebocyte lysate assay and gas
      chromatography-mass spectrum analysis of lipopolysaccharides relative to nitric
      oxide production by peritoneal exudates of cells.
AB  - Limulus amebocyte lysate (LAL) assay and gas chromatography-mass spectrum (GC-MS)
      analysis are usually used for the quantification of lipopolysaccharides (LPS)
      from the environment. The LAL assay measures endotoxin units to represent the LPS
      biological function but GC-MS analysis measures decanoic (C(10:0)) and dodecanoic
      (C(12:0)) 3-hydorxy fatty acids (3-OH FA) concentration to represent the LPS
      chemical composition. A study was carried out using these methods to evaluate
      their degree of correlation. Using the culture supernatants of 30 independent
      strains of Pseudomonas aeruginosa, the bacterial supernatants gave of 0.53+/-0.45
      and 2.49+/-1.75mg/l of C(10:0) and C(12:0) 3-OH FA, respectively, compared to
      17.96+/-13.28mg/l of LPS with the LAL assay (1ng/ml of LPS congruent
      with0.78EU/ml). The 3-OH FA concentration relative to the endotoxin unit dose in
      the supernatants exhibited a positive correlation (r(2)=0.5182, C(10:0);
      r(2)=0.4359, C(12:0)). When supernatants having a high level of endotoxin were
      used to treat peritoneal exudates cells, nitric oxide (NO) was generated in a
      dose-dependent manner (r(2)=0.6174). To determine if either C(10:0) or C(12:0) 3
      OH FA can act as an indictor of LPS quantity was correlated with this
      immunostimulatory effect, the correlation of these 3-OH FA concentrations against
      the produced NO levels was evaluated. This also exhibited a positive correlation;
      however, the two indicators of 3-OH FA gave different dose-responsible
      performances (r(2)=0.3211, C(10:0); r(2)=0.4527, C(12:0)).

PMID- 17188812
TI  - Hexavalent chromium reduction by Acinetobacter haemolyticus isolated from heavy
      metal contaminated wastewater.
AB  - Possible application of a locally isolated environmental isolate, Acinetobacter
      haemolyticus to remediate Cr(VI) contamination in water system was demonstrated.
      Cr(VI) reduction by A. haemolyticus seems to favour the lower concentrations (10
      30 mg/L). However, incomplete Cr(VI) reduction occurred at 70-100 mg/L Cr(VI).
      Initial specific reduction rate increased with Cr(VI) concentrations. Cr(VI)
      reduction was not affected by 1 or 10 mM sodium azide (metabolic inhibitor), 10
      mM of PO(4)3-, SO4(2-), SO(3)2-, NO3- or 30 mg/L of Pb(II), Zn(II), Cd(II) ions.
      However, heat treatment caused significant dropped in Cr(VI) reduction to less
      than 20% only. A. haemolyticus cells loses its shape and size after exposure to
      10 and 50 mg Cr(VI)/L as revealed from TEM examination. The presence of electron
      dense particles in the cytoplasmic region of the bacteria suggested deposition of
      chromium in the cells.

PMID- 17188813
TI  - Adjusting worm egg counts for faecal moisture in sheep.
AB  - The number of eggs from gastrointestinal nematodes per gram of faeces (worm egg
      count WEC) is commonly used to determine the need for anti-parasite treatments
      and the breeding value of animals when selecting for worm resistance. Diarrhoea
      increases faecal moisture and may dilute the number of worm eggs observed. To
      quantify this effect, egg counts in sheep at pasture were simulated by dosing 15
      animals with chromic oxide particles. The simulated WEC diminished as faecal
      moisture increased. When faeces were dried, simulated WEC per unit dry matter was
      not influenced by the amount of faecal moisture present prior to drying. The
      results suggest that adjustment for faecal moisture may provide an improved
      estimate of FEC. Drying faeces to calculate the WEC per unit dry matter would
      provide such an adjustment but may not be practical for industry application. In
      the past, the CSIRO McMaster Laboratory has used an adjustment factor developed
      by Gordon based on the classification of faecal consistency derived from the
      morphology of faeces. To examine the utility of an adjustment factor based on
      faecal consistency score (FCS), the relationships between FCS and simulated WEC
      and dry matter were examined. Dry matter and simulated WEC exhibited an
      exponential decline as FCS increased. The relationship between FCS and dry matter
      was further examined in 368 samples collected over 12 months from sheep at
      pasture, where it was observed that dry matter showed a linear decline as FCS
      increased. Adjustment factors based on dry matter were similar to those proposed
      by Gordon however adjustment factors predicted from simulated WEC diverged from
      the remainder for FCS>4. As no samples scored FCS 5 in the study of simulated
      FEC, the adjustment factors based on the larger study that included samples with
      FCS 5 was therefore considered more robust. Adjustment factors were given by the
      equation: WEC(estimated)=(WEC(observed)/(34.21-5.15 FCS))x29.06. This equation
      estimates for samples with FCS>1 the WEC that would be expected if the samples
      were FCS 1, the faecal consistency score for normal faeces. The impact of
      adjustment of observed WEC for faecal moisture predicted by FCS on decision
      points for treatment and on estimated breeding values requires further
      examination.

PMID- 17188814
TI  - Expression of angiogenic and neurotrophic factors in the progenitor cell niche of
      adult monkey subventricular zone.
AB  - The subventricular zone along the anterior horn (SVZa) of the cerebral lateral
      ventricle of adult mammals contains multipotent progenitor cells, which
      supposedly exist in an angiogenic niche. Numerous signals are known to modulate
      the precursor cell proliferation, migration or differentiation, in rodent models.
      In contrast, the data on signals regulating the primate SVZa precursors in vivo
      are scarce. We analyzed the expression at protein level of a panel of angiogenic
      and/or neurotrophic factors and their receptors in SVZa of adult macaque monkeys,
      under normal condition or after transient global ischemia which enhances
      endogenous progenitor cell proliferation. We found that fms-like tyrosine kinase
      1 (Flt1), a receptor for vascular endothelial cell growth factor, was expressed
      by over 30% of the proliferating progenitors, and the number of Flt1-positive
      precursors was significantly increased by the ischemic insult. Smaller fractions
      of mitotic progenitors were positive for the neurotrophin receptor tropomyosin
      related kinase (Trk) B or the hematopoietic receptor Kit, while immature neurons
      expressed Flt1 and the neurotrophin receptor TrkA. Further, SVZa astroglia,
      ependymal cells and blood vessels were positive for distinctive sets of
      ligands/receptors, which we characterized. The presented data provide a molecular
      phenotypic analysis of cell types comprising adult monkey SVZa, and suggest that
      a complex network of angiogenic/neurotrophic signals operating in an autocrine or
      paracrine manner may regulate SVZa neurogenesis in the adult primate brain.

PMID- 17188815
TI  - Adolescent peer group identification and characteristics: a review of the
      literature.
AB  - This study provides an exhaustive review of 44 peer-reviewed quantitative or
      qualitative data-based peer-reviewed studies completed on adolescent peer group
      identification. Adolescent peer group identification is one's self-perceived or
      other-perceived membership in discrete teenage peer groups. The studies reviewed
      suggest that adolescent peer groups consist of five general categories
      differentiable by lifestyle characteristics: Elites, Athletes, Academics,
      Deviants, and Others. We found that the Deviant adolescent group category
      reported relatively greater participation in drug use and other problem behaviors
      across studies, whereas Academics and Athletes exhibited the least participation
      in these problem behaviors. Additional research is needed in this arena to better
      understand the operation of adolescent group labels.

PMID- 17188816
TI  - Precipitants of first substance use in recently abstinent substance use disorder
      patients with PTSD.
AB  - Patients with substance use (SUD) and posttraumatic stress disorders (PTSD) are
      at high risk for relapse. This study examined the reasons patients identify for
      their first substance use following discharge from SUD treatment. A total of 65
      patients with and without PTSD completed clinical interviews, including an
      adapted version of the Relapse Interview [RI; Miller, W.R., & Marlatt, G.A.
      (1996). Appendix A: Relapse Interview. Addiction, 91(Suppl), 231-240.] at a 6
      month follow-up. Qualitative data from the RI was consensus coded using Marlatt's
      taxonomy of relapse situations. Results indicated that patients with PTSD were
      less likely to report first substance use triggered by cue-based urges and more
      likely to report use in response to negative emotions of an interpersonal nature
      than those patients without PTSD. Other characteristics of first use associated
      with PTSD included greater subjective urges right before using, greater efforts
      to obtain substances and more likelihood to use to intoxication. Patients with
      unremitted PTSD reported poorer outcome and self-efficacy expectations than those
      without PTSD or with remitted PTSD. Implications for self-medication theory and
      clinical practice are discussed.

PMID- 17188817
TI  - How to find future ecstasy-users: targeted and snowball sampling in an ethically
      sensitive context.
AB  - This article documents the design and the sampling procedures of a prospective
      longitudinal multidisciplinary study on the neurotoxicity of ecstasy (MDMA): the
      Netherlands XTC Toxicity Study (NeXT). Targeted and snowball sampling was used to
      recruit 188 respondents who were ecstasy-naive at baseline. All respondents
      completed baseline questionnaires and underwent medical and neuropsychological
      examinations. At the end of a 11- to 26- month follow-up period in which they
      completed four additional questionnaires, 160 respondents remained (85.1%). A
      total of 65 participants (40.6%) took ecstasy for the first time during the
      follow-up period. This paper discusses the ethical dilemmas inherent in a study
      of this type and the specific problems and solutions that emerged in the
      sampling. The sampling was tightly constrained by our need to locate respondents
      who were potential future ecstasy users while also meeting strict medical and
      technical criteria. The 'intention to use' criterion proved to be a clear-cut
      inclusion rule that was practical to apply in the fieldwork.

PMID- 17188818
TI  - Perceived peer influence and peer selection on adolescent smoking.
AB  - Despite advances in tobacco control, adolescent smoking remains a problem. The
      smoking status of friends is one of the highest correlates with adolescent
      smoking. This homophily (commonality of friends based on a given attribute) may
      be due to either peer pressure, where adolescents adopt the smoking behaviors of
      their friends, or peer selection, where adolescents choose friends based on their
      smoking status. This study used structural equation modeling to test a model of
      peer influence and peer selection on ever smoking by adolescents. The primary
      analysis of the model did not reach significance, but post hoc analyses did
      result in a model with good fit. Results indicated that both peer influence and
      peer selection were occurring, and that peer influence was more salient in the
      population than was peer selection. Implications of these results for tobacco
      prevention programs are discussed.

PMID- 17188819
TI  - Identification of CCAAT enhancer binding protein alpha binding sites on the human
      alpha-fetoprotein gene.
AB  - Development- and tissue-specific alpha-fetoprotein (AFP) gene expression is
      controlled by various transcription factors including hepatocyte nuclear factors
      (HNFs), and a number of cis-acting elements. We recently identified multiple
      CCAAT/enhancer binding protein (C/EBP) binding sites in the enhancer of the human
      AFP gene. In this study, we have identified and functionally characterized seven
      C/EBPalpha-binding sites in the promoter and enhancer regions. An electrophoretic
      mobility shift assay (EMSA) and DNase I footprinting analysis identified two and
      five C/EBPalpha-binding sites located in the promoter and enhancer regions,
      respectively. Chromatin immunoprecipitation analyses showed that C/EBPalpha binds
      both enhancer and promoter regions of the AFP gene in human AFP-producing
      hepatoma and stomach cancer cells, but not in non-AFP-producing cells. Reporter
      transfection assays showed that transcription was stimulated by C/EBPalpha
      binding to each of the elements. These results indicate that C/EBPalpha regulates
      AFP gene expression through direct binding to multiple sites in the human AFP
      gene in cultured human cells.

PMID- 17188820
TI  - Genetic rearrangement of the atzAB atrazine-degrading gene cassette from
      pADP1::Tn5 to the chromosome of Variovorax sp. MD1 and MD2.
AB  - We report the characterization of the rearrangement phenomena responsible for the
      movement of the atrazine-degrading atzA and B genes from pADP1::Tn5 to the
      chromosome of Variovorax sp. MD1 and MD2. Long PCRs and Southern blot analyses
      revealed that the two genes forming a gene cassette moved in a unique
      rearrangement event. It also revealed that the boundaries of the plasmid sequence
      inserted in the chromosome correspond to IS1071or to sequences close to IS1071.
      It suggests that this genetic rearrangement could result from the transposition
      of the composite transposon delimited by IS1071 insertion sequences and
      containing atzA and atzB genes. In addition, for MD1 and MD2 strains the
      sequencing of the remaining sequence on pADP1::Tn5 indicated that the deletion of
      the atzA and B genes from the plasmid might be the result of a recombination
      event that occurred between the IS1071 insertion sequences surrounding the atzAB
      gene cassette.

PMID- 17188821
TI  - Genome ecosystem and transposable elements species.
AB  - Transposable elements are known to be "selfish DNA" sequences able to spread and
      be maintained in all genomes analyzed so far. Their evolution depends on the
      interaction they have with the other components of the genome, including genes
      and other transposable elements. These relationships are complex and have often
      been compared to those of species living and competing in an ecosystem. The aim
      of this current work is a proposition to fill the conceptual gap existing between
      genome biology and ecology, assuming that genomic components, such as
      transposable elements families, can be compared to species interacting in an
      ecosystem. Using this framework, some of the main models defined in the
      population genetics of transposable elements can then been reformulated, and some
      new kinds of realistic relationships, such as symbiosis between different genomic
      components, can then be modelled and explored.

PMID- 17188822
TI  - Re-challenge of pigs following recovery from proliferative enteropathy.
AB  - An experimental challenge model was developed to demonstrate Lawsonia
      intracellularis colonization and reproduction of proliferative enteropathy (PE)
      in naive weaner pigs. Groups of pigs were orally dosed with between 10(10) and
      10(5)L. intracellularis extracted from haemorrhagic PE affected mucosa. Pigs were
      monitored for clinical signs and intestinal lesions of PE and evidence of
      bacterial colonization by serology and faecal polymerase chain reaction (PCR).
      One group of challenged pigs were necropsied after 21 days to confirm the
      reproduction of PE. L. intracellularis colonization and seroconversion was
      delayed in pigs dosed with lower numbers of L. intracellularis. When faecal
      shedding of L. intracellularis ceased to be detected in all of the challenged
      pigs, they were re-dosed orally with approximately 10(10)L. intracellularis and
      monitored for evidence of re-colonization and clinical disease. This study
      demonstrated that pigs previously challenged with L. intracellularis were
      protected from re-colonization and clinical disease on subsequent exposure 10
      weeks later, regardless of the initial dose of L. intracellularis.

PMID- 17188823
TI  - Absence of surface expression of feline infectious peritonitis virus (FIPV)
      antigens on infected cells isolated from cats with FIP.
AB  - Feline infectious peritonitis virus (FIPV) positive cells are present in
      pyogranulomas and exudates from cats with FIP. These cells belong mainly to the
      monocyte/macrophage lineage. How these cells survive in immune cats is not known.
      In this study, FIPV positive cells were isolated from pyogranulomas and exudates
      of 12 naturally FIPV-infected cats and the presence of two immunologic targets,
      viral antigens and MHC I, on their surface was determined. The majority of the
      infected cells were confirmed to be cells from the monocyte/macrophage lineage.
      No surface expression of viral antigens was detected on FIPV positive cells. MHC
      I molecules were present on all the FIPV positive cells. After cultivation of the
      isolated infected cells, 52+/-10% of the infected cells re-expressed viral
      antigens on the plasma membrane. In conclusion, it can be stated that in FIP
      cats, FIPV replicates in cells of the monocyte/macrophage lineage without
      carrying viral antigens in their plasma membrane, which could allow them to
      escape from antibody-dependent cell lysis.

PMID- 17188824
TI  - Incidence and risk factors for cerebral palsy in infants with perinatal problems:
      a 15-year review.
AB  - OBJECTIVE: Cerebral palsy (CP) is associated with prenatal, perinatal and
      postnatal factors. This is a retrospective case-control study aiming to determine
      the frequency of CP and examine risk factors for CP among infants cared for in
      the Neonatal Intensive Care Unit (NICU) covering Northwest Greece. DESIGN AND
      PATIENTS: All neonates who were admitted to the NICU during the period 1989-2003
      inclusive, and subsequently developed CP, were enrolled in the study, with
      matched controls. The incidence of CP was evaluated according to gestational age
      (GA): GA<34 weeks (group A) and GA>34 (group B), and study period: 1989-1996
      (period I) and 1997-2003 (period II, during which intrauterine transfer and
      prenatal steroids were used). RESULTS: CP was diagnosed in 78 children, 55 in
      group A and 23 in group B. The incidence of CP increased significantly with
      decreasing GA. Survival without CP increased significantly in children of GA<34
      weeks during period II. The main factors associated with CP, identified by
      multivariate analysis, were (odds ratios, confidence interval), for group A:
      being small for gestational age (SGA) (2.5, 1.2-4.5) and patent ductus arteriosus
      (PDA) (3.4, 1.3-9.2) in period I, periventricular leucomalacia (PVL) (27, 4.8
      209), prolonged rupture of membranes (PROM) (5.6, 1.8-18) and duration of
      mechanical ventilation (1.1, 1.05-1.2) in period II, and for group B: SGA (3.6,
      1.3-9.9), neonatal transfer (3.06, 1.2-7.6), duration of mechanical ventilation
      (1.1, 1.06-1.25) and sepsis-meningitis (4.3, 1.2-16). CONCLUSION: Improvement in
      survival without CP was observed in infants of GA<34 weeks during the later
      period of the study, and risk factors for CP in preterm infants depended on the
      study period. PVL, PROM and PDA were the most powerful independent predictors of
      CP in children of GA<34 weeks and SGA, neonatal transfer and sepsis/meningitis in
      children of GA>34 weeks.

PMID- 17188825
TI  - Effects of PM2.5 components in the release of amphiregulin by human airway
      epithelial cells.
AB  - Exposure to ambient particulate matter (PM) is responsible for airway
      inflammation and tissue remodeling. Urban PM(2.5) (aerodynamic diameter
      <2.5microm) is a complex mixture rich in soots and containing hydrosoluble and
      organic components. We previously showed that the exposure of airway epithelial
      cells to PM(2.5) triggers the release of amphiregulin (AR), ligand of the
      epidermal growth factor receptor (EGFR) involved in proinflammatory and repair
      responses. The effect of Paris PM(2.5) organic and aqueous fractions in AR
      expression and secretion was investigated on the bronchial epithelial cell line
      16HBE and normal human nasal epithelial (NHNE) cells. Both a macroarray specific
      for inflammation pathways and RT-PCR showed an AR upregulation in organic extract
      treated 16HBE cells. AR release is induced in 16HBE and NHNE cells grown on
      plastic and exposed to native PM(2.5), organic extract and to a lesser extent
      washed PM(2.5) (deprived of its hydrosoluble content) and aqueous extract.
      Furthermore, as assessed by using NHNE cells grown on Transwell inserts, this
      secretion is polarized toward the basolateral side where the EGFR is expressed.
      To conclude, both PM(2.5) organic and hydrosoluble components are involved in the
      expression and secretion of AR; organic compounds exhibiting a strong effect when
      they are easily bioavailable.

PMID- 17188826
TI  - Inhibitory effects of Hu-qi-yin on the bleomycin-induced pulmonary fibrosis in
      rats.
AB  - The currently accepted approaches to treatment of pulmonary fibrosis are based on
      the treatment of alveolitis and pulmonary fibrosis, however clinically available
      anti-inflammatory and antifibrotic agents are not often beneficial. Hu-qi-yin,
      one of the traditional Chinese herbal formulas, has been used for clinical
      therapy of pulmonary fibrosis in China. The aim of the present study is to
      evaluate the preventive effects of Hu-qi-yin on the bleomycin (BLM)-induced
      pulmonary fibrosis in rats. The degree of fibrosis was evaluated with
      hydroxyproline contents in serum and lung tissue 28 days post-BLM instillation.
      The semi-quantitative analyses of lung sections were conducted to evaluate the
      intensity of alveolitis and fibrosis. Furthermore, the expression of transforming
      growth factor-beta(1) (TGF-beta(1)) was quantitatively studied at the protein and
      mRNA levels by immunohistochemistry and in situ hybridization, respectively. Oral
      treatment with Hu-qi-yin improved the body weight loss of rats in doses of 3.8,
      7.6g/kg compared with BLM-treated control group, and significantly inhibited the
      alveolitis and pulmonary fibrosis in a dose-dependent manner as reflected by
      decreases of the hydroxyproline contents of serum and lung, and amelioration of
      alveolitis and pulmonary fibrosis fraction 28 days after BLM administration. The
      one of the possible mechanisms of the protective effect of Hu-qi-yin was via
      reduction of the overexpression of TGF-beta(1) protein and mRNA. These results
      suggested a great potential that Hu-qi-yin might be effective in the treatment of
      pulmonary fibrosis.

PMID- 17188827
TI  - Monitoring precursor chemicals of methamphetamine through enantiomer profiling.
AB  - Smuggling of methamphetamine is affected by enforced regulation and international
      situation, resulting in changes of precursors and synthetic methods used.
      Enantiomer ratio of methamphetamine can provide information concerning its
      precursor and synthetic method. This information is useful for the prevention of
      smuggling methamphetamine and its precursor, and resultant reduction of
      methamphetamine abuse. In the present study, we investigated on the enantiomer
      ratios of 433 crystalline methamphetamine samples seized in Korea from 1994 to
      2005. Excluding 17 samples of low purity, 416 samples were used for enantiomer
      profiling. The methamphetamine samples were derivatized with (S)-(+)-alpha
      methoxy-alpha-(trifluoromethyl)phenylacetyl chloride ((S)-(+)-MTPACl), and the
      derivatives were analyzed by GCMS in selected ion monitoring (SIM) mode. The
      enantiomer ratios of the samples were calculated from the standard calibration
      curves of each enantiomer, both of which showed good linearity in the range of 0
      1.2 microg. Most of the seizures were pure S(+)-enantiomer, but 21% (95 of 416
      samples) contained R(-)-enantiomer above 1%. They began to appear from 1997, and
      increased continuously up to 50% in the year 2005 (55 of 111 samples). From this
      study, we could find out that alternative precursors have been used recently for
      the illicit manufacture of methamphetamine seized in Korea.

PMID- 17188828
TI  - Endoanal ultrasound evaluation of anorectal diseases and disorders: technique,
      indications, results and limitations.
AB  - Imaging of the rectum, anorectal junction and surrounding tissues is both
      difficult and technically challenging. CT and conventional barium studies offer
      limited information in local staging of rectal and perirectal neoplasms, anal
      carcinomas and extension perianal fistulas in patients with inflamamatory bowel
      disease, or in evaluating patients with fecal incontinence. During past decade,
      sonography and MR imaging have resulted in significant improvement in the imaging
      of rectal and perirectal and anal and perianal disease. The aim of this article
      is to review possibility of the EAUS in the evaluation both normal anal anatomy
      and anorectal disease and disorders (anal carcinoma, sphincter defects, anal
      fistulas, perianal abscesses and other pathological conditions).

PMID- 17188829
TI  - Validation of image quality in full-field digital mammography: is the replacement
      of wet by dry laser printers justified?
AB  - OBJECTIVE: Dry laser printers have replaced wet laser printers to produce hard
      copies of high-resolution digital images, primarily because of environmental
      concerns. However, no scientific research data have been published that compare
      the image quality of dry and wet laser printers in full-field digital mammography
      (FFDM). This study questions the image quality of these printers. MATERIALS AND
      METHODS: Objective image quality parameters of both printers were evaluated using
      a standardized printer test image, i.e., optical density and detectability of
      specific image elements (lines, curves, and shapes). Furthermore, mammograms of
      129 patients with different breast tissue composition patterns were imaged with
      both printers. A total of 1806 subjective image quality parameters (brightness,
      contrast, and detail detection of anatomic structures), the detectability of
      breast lesions, as well as diagnostic performance according to the BI-RADS
      classification were evaluated. In addition, the presence of film artifacts was
      investigated. RESULTS: Optical density values were equal for the dry and the wet
      laser printer. Detection of specific image elements on the printer test image was
      not different. Ratings of subjective image quality parameters were equal, as were
      the detectability of breast lesions and the diagnostic performance. Dry laser
      printer images showed more artifacts (164 versus 27). However, these artifacts
      did not influence image quality. CONCLUSION: Based on the evidence of objective
      and subjective parameters, a dry laser printer equals the image quality of a wet
      laser printer in FFDM. Therefore, not only for reasons of environmental
      preference, the replacement of wet laser printers by dry laser printers in FFDM
      is justified.

PMID- 17188830
TI  - Endometrial biopsy by means of the hysteroscopic resectoscope for the evaluation
      of tumor differentiation in endometrial cancer: a pilot study.
AB  - AIMS: To assess the diagnostic accuracy of endometrial biopsy by means of the
      hysteroscopic resectoscope (EBHR) in evaluating tumor differentiation in patients
      with endometrial cancer. METHODS: Between January and December 2005, all the
      women with a diagnosis of endometrioid adenocarcinoma of the uterus, when
      admitted to hospital, were enrolled for this study. Patients eligible for
      surgical treatment underwent a preoperative work-up consisting in pelvic magnetic
      resonance imaging (MRI) and EBHR. In all patients submitted to a hysterectomy, a
      comparison between pre- and postoperative tumor grade was carried out. RESULTS:
      42 women were enrolled in the study. Hysteroscopic biopsy was carried out in 39
      patients (mean age 62.5 years, range 33-79; FIGO stage I: 34, stage II-IV: 5). No
      complication related to hysteroscopy was observed. The preoperative tumor grade
      by hysteroscopy correlated with the final grade in 97.1% of cases. No patient had
      positive peritoneal washing and after a median follow-up of ten months no
      intraperitoneal tumor relapse was observed. CONCLUSION: EBHR is a very accurate
      diagnostic procedure for assessing the preoperative tumor grade in patients with
      endometrial cancer.

PMID- 17188831
TI  - Emerging pollen allergens.
AB  - Numerous pollen allergens have been reported over the last few years. Most of
      them belong to well-known families of proteins but some others constitute the
      first member of new allergenic families. Some of the factors that can contribute
      to the detection and identification of new pollen allergens are: a) advances in
      the technology tools for molecular analysis; and b) the deep knowledge of many
      allergenic sources. The combination of these factors has provided vast
      information on the olive pollen allergogram and the identification of minor
      allergens that become major ones for a significant population. The close
      taxonomical relationship between olive tree and ash -both Oleaceae- has permitted
      to identify Fra e 1 (the Ole e 1-like allergen) in ash pollen and to detect the
      presence of protein homologues of Ole e 3 and Ole e 6. In the other hand,
      extensive areas of south Europe are suffering an increasing desertification. As a
      consequence of this, new botanical species are spontaneously growing in these
      areas or being used in greening ground programs: Chenopodium album and Salsola
      kali are some examples recently recognized as allergenic woods. The
      identification of the complete panel of allergens from the hypersensitizing
      sources might help to develop more accurate diagnosis, and efficient and safer
      therapy tools for Type-I allergic diseases.

PMID- 17188832
TI  - Antimicrobial strategies: an option to treat allergy?
AB  - Respiratory infections by bacteria and viruses often trigger symptoms of asthma
      in both adults and children. This observation and subsequent mechanistic studies
      have demonstrated important interactions among allergens, microbes and the atopic
      host. The mechanisms responsible for microbe-induced asthma exacerbations are
      only incompletely understood. A focal point of current research is the
      inflammatory response of the host following an encounter with a pathogenic
      microbe, including variations in chemokine and cytokine production and resulting
      in changes in bronchial hyper-responsiveness and lung function. Direct bronchial
      infection, exposure of nerves with resulting neurogenic inflammation and a
      deviated host immune response are among the mechanisms underlying these
      functional disorders. Lately, suboptimal innate immune responses, expressed as
      defective interferon production, have gained attention as they might be amenable
      to intervention. This review describes the suggested mechanisms involved in the
      complex interactions between 'asthmagenic' microbes, the immune system and atopy,
      based on in-vitro and in-vivo experimental models and epidemiological evidence.
      In addition, it provides a synopsis of potential therapeutic strategies either
      directly against the microorganisms or in respect to the associated inflammation.

PMID- 17188833
TI  - The intrinsic flexibility of IgE and its role in binding FcepsilonRI.
AB  - The interaction between IgE and its high affinity cellular receptor (FcepsilonRI)
      is an essential step in the development of allergic responses. Studies have
      identified the third constant domain of IgE (Cepsilon3) as the receptor binding
      region. The Cepsilon3 domain has unusual structural features; it was found to be
      a 'molten globule' structure in an isolated form, only assuming a well structured
      form upon binding to FcepsilonRI. The conformational flexibility intrinsic to the
      receptor binding portion of the molecule may be useful to IgE in allowing the
      large allosteric changes postulated to be required for FcepsilonRI engagement. If
      allosteric inhibitors can be developed then the dynamic properties of the
      Cepsilon3 domain may provide opportunities for therapeutic intervention in
      allergic disorders.

PMID- 17188834
TI  - Differential contribution of the residues in C-terminal half of the heavy chain
      of botulinum neurotoxin type B to its binding to the ganglioside GT1b and the
      synaptotagmin 2/GT1b complex.
AB  - Clostridium botulinum type B neurotoxin was effectively bound to synaptotagmin 2
      (Stg2) associated with ganglioside GT1b, however, the molecular interaction
      between the neurotoxin and the Stg2/GT1b complex has not been identified.
      Previously, we found that infant botulism-related strain 111 generated a low
      activity of the neurotoxin (111/NT), which differed in some amino acid residues,
      especially in the carboxyl terminal half of the heavy chain (H(C)), from the
      original neurotoxin of strain Okra (Okra/NT) associated with a food-borne
      botulism. In this study, we evaluated the binding capabilities of site-directed
      mutants of Okra/H(C) to the Stg2/GT1b complex and to GT1b alone, and investigated
      the relationship between the toxic action and receptor binding. Replacement of
      K1187 and E1190 with glutamic acid and lysine, respectively, which substituted
      for the 111/NT residues, caused a reduction of binding affinity to the Stg2/GT1b
      complex, suggesting that both these residues contribute to the different binding
      affinity between Okra/NT and 111/NT. Substitution of four residues, H1240, S1259,
      W1261 and Y1262, which form a ganglioside pocket, drastically decreased the
      binding of H(C) to the Stg2/GT1b complex and to GT1b. Mutation in the residues,
      K1186, E1189, K1191 and K1260 reduced the binding of H(C) to GT1b alone, but not
      to the Stg2/GT1b complex. Analyses of effects of mutant toxins on toxicity of
      BoNT/B to cerebellar granule cells suggest the association of cell toxicity with
      binding to Stg2/GT1b complex but not that to GT1b alone.

PMID- 17188835
TI  - Estimating constants for metabolism of atrazine in freshly isolated rat
      hepatocytes by kinetic modeling.
AB  - This study estimated the kinetic constants for oxidative metabolism of atrazine
      (ATRA) and its chlorotriazine (Cl-TRI) metabolites, 2-chloro-4-ethylamino-6-amino
      1,3,5-triazine (ETHYL), 2-chloro-4-amino-6-isopropylamino-1,3,5-triazine (ISO),
      and diaminochlorotriazine (DACT), using freshly isolated rat hepatocytes.
      Hepatocytes were incubated with 1.74, 44, 98, and 266 microM ATRA. Disappearance
      of ATRA and formation of the Cl-TRI metabolites were quantified over 90 min. At
      all incubation concentrations, ATRA was preferentially metabolized to ETHYL,
      producing ETHYL concentrations approximately 6 times higher than those of ISO.
      DACT concentrations peaked at 44 microM ATRA and decreased with increasing
      incubation concentrations, indicating non-linear metabolic behavior of ATRA with
      respect to DACT formation. A series of kinetic models were developed from these
      data to describe the dose and time-dependent oxidative metabolism of ATRA and the
      Cl-TRI metabolites. An integrated model for all the chloro-triazines included
      multi-substrate competitive inhibition of metabolism to describe the non-linear
      behavior of DACT production in relation to ATRA while simultaneously simulating
      the time-course behavior of the Cl-TRIs at all four ATRA concentrations. The
      maximal metabolic rate (V(max)) of ATRA metabolism and the Michaelis-Menten
      constant (K(M)) for the reaction were 1.6 microM/min and 30 microM, respectively.
      V(max) and K(M) values for ETHYL and ISO metabolism to DACT were also estimated
      using this modeling approach.

PMID- 17188836
TI  - Trends in the development of microfluidic cell biochips for in vitro
      hepatotoxicity.
AB  - Current developments in the technological fields of liver tissue engineering,
      bioengineering, biomechanics, microfabrication and microfluidics have lead to
      highly complex and pertinent new tools called "cell biochips" for in vitro
      toxicology. The purpose of "cell biochips" is to mimic organ tissues in vitro in
      order to partially reduce the amount of in vivo testing. These "cell biochips"
      consist of microchambers containing engineered tissue and living cell cultures
      interconnected by a microfluidic network, which allows the control of
      microfluidic flows for dynamic cultures, by continuous feeding of nutrients to
      cultured cells and waste removal. Cell biochips also allow the control of
      physiological contact times of diluted molecules with the tissues and cells, for
      rapid testing of sample preparations or specific addressing. Cell biochips can be
      situated between in vitro and in vivo testing. These types of systems can enhance
      functionality of cells by mimicking the tissue architecture complexities when
      compared to in vitro analysis but at the same time present a more rapid and
      simple process when compared to in vivo testing procedures. In this paper, we
      first introduce the concepts of microfluidic and biochip systems based on recent
      progress in microfabrication techniques used to mimic liver tissue in vitro. This
      includes progress and understanding in biomaterials science (cell culture
      substrate), biomechanics (dynamic cultures conditions) and biology (tissue
      engineering). The development of new "cell biochips" for chronic toxicology
      analysis of engineered tissues can be achieved through the combination of these
      research domains. Combining these advanced research domains, we then present
      "cell biochips" that allow liver chronic toxicity analysis in vitro on engineered
      tissues. An extension of the "cell biochip" idea has also allowed "organ
      interactions on chip", which can be considered as a first step towards the
      replacement of animal testing using a combined liver/lung organ model.

PMID- 17188837
TI  - The role of climate in human mitochondrial DNA evolution: a reappraisal.
AB  - Previous studies have proposed that selection has been involved in the
      differentiation of human mitochondrial DNA (mtDNA) and climate was the main
      driving force. This viewpoint, however, gets no support from the subsequent
      studies and remains controversial thus far. To clarify this issue, a total of 237
      complete mtDNA sequences belonging to autochthonous lineages from South Asia,
      Oceania, and East Asia were collected to seek for the imprint of selection. Based
      on nonsynonymous (N) and synonymous (S) substitutions analysis, our results
      confirmed that purifying selection was the predominant force during the evolution
      of human mtDNA. However, no significant and extensive difference was detected
      among these three regions, which did not support the climate adaptation
      hypothesis but preferred random genetic drift to be the main factor in shaping
      the current landscape of human mtDNA, at least those from Asian and Oceanian
      regions.

PMID- 17188839
TI  - Empirical comparison of tests for differential expression on time-series
      microarray experiments.
AB  - Methods for identifying differentially expressed genes were compared on time
      series microarray data simulated from artificial gene networks. Select methods
      were further analyzed on existing immune response data of Boldrick et al. (2002,
      Proc. Natl. Acad. Sci. USA 99, 972-977). Based on the simulations, we recommend
      the ANOVA variants of Cui and Churchill. Efron and Tibshirani's empirical Bayes
      Wilcoxon rank sum test is recommended when the background cannot be effectively
      corrected. Our proposed GSVD-based differential expression method was shown to
      detect subtle changes. ANOVA combined with GSVD was consistent on background
      normalized simulation data. GSVD with empirical Bayes was consistent without
      background correction. Based on the Boldrick et al. data, ANOVA is best suited to
      detect changes in temporal data, while GSVD and empirical Bayes effectively
      detect individual spikes or overall shifts, respectively. For methods tested on
      simulation data, lowess after background correction improved results. On
      simulation data without background correction, lowess decreased performance
      compared to median centering.

PMID- 17188840
TI  - Smoking during pregnancy: subsequent effects on offspring immune competence and
      disease vulnerability in later life.
AB  - About 1 million babies are born each year after prenatal cigarette smoke (CS)
      exposure from maternal smoking which does not include involuntary maternal
      exposure to passive smoke. While past emphasis has been on immediately obvious
      perinatal consequences (e.g., preterm delivery, and low birthweight), smoking
      during pregnancy has recently emerged as a possible risk factor for later onset
      disease outcomes in the prenatally exposed offspring. This review brings together
      those epidemiologic and toxicologic studies demonstrating a link between prenatal
      CS exposure and subsequent disease vulnerabilities in the progeny. While
      disorders such as obesity, and type 2 diabetes are included in this category,
      this paper focuses on two immunologically-related outcomes, cancer and asthma.
      The review defines the current state of knowledge in this understudied area of
      children's health, sheds light on the seriousness of such disease
      vulnerabilities, and reveals gaps that need to be filled to provide a better
      understanding of the extent and nature of the problem.

PMID- 17188838
TI  - Analysis of tissue-specific differentially methylated regions (TDMs) in humans.
AB  - Alterations in DNA methylation have been implicated in mammalian development.
      Hence, the identification of tissue-specific differentially methylated regions
      (TDMs) is indispensable for understanding its role. Using restriction landmark
      genomic scanning of six mouse tissues, 150 putative TDMs were identified and 14
      were further analyzed. The DNA sequences of the 14 mouse TDMs are analyzed in
      this study. Six of the human homologous regions show TDMs to both mouse and human
      and genes in five of these regions have conserved tissue-specific expression:
      preferential expression in testis. A TDM, DDX4, is further analyzed in nine
      testis tissues. An increase in methylation of the promoter region is
      significantly associated with a marked reduction of the gene expression and
      defects in spermatogenesis, suggesting that hypomethylation of the DDX4 promoter
      region regulates DDX4 gene expression in spermatogenic cells. Our results
      indicate that some genomic regions with tissue-specific methylation and
      expression are conserved between mouse and human and suggest that DNA methylation
      may have an important role in regulating differentiation and tissue-/cell
      specific gene expression of some genes.

PMID- 17188841
TI  - 3D soft tissue imaging with a mobile C-arm.
AB  - We introduce a clinical prototype for 3D soft tissue imaging to support surgical
      or interventional procedures based on a mobile C-arm. An overview of required
      methods and materials is followed by first clinical images of animals and human
      patients including dosimetry. The mobility and flexibility of 3D C-arms gives
      free access to the patient and therefore avoids relocation of the patient between
      imaging and surgical intervention. Image fusion with diagnostic data (MRI, CT,
      PET) is demonstrated and promising applications for brachytherapy, RFTT and
      others are discussed.

PMID- 17188842
TI  - Diagnostic Interview for Genetic Studies (DIGS): inter-rater and test-retest
      reliability and validity in a Spanish population.
AB  - OBJECTIVE: To test the reliability and validity of the DIGS in Spanish
      population. METHODS: Inter-rater and test-retest reliability of the Spanish
      version of DIGS was tested in 95 inpatients and outpatients. The resultant
      diagnoses were compared with diagnoses obtained by the LEAD (Longitudinal Expert
      All Data) procedure as "gold standard". The kappa statistic was used to measure
      concordance between blind inter-raters and between the diagnoses obtained by LEAD
      procedure and through the DIGS. RESULTS: Overall kappa coefficient for inter
      rater reliability was 0.956. The kappa value for individual diagnosis varied from
      major depression=0.877 to schizophrenia=1. Test-retest reliability was 0.926.
      Kappa for all individual target diagnoses ranged from 0.776 (major depression) to
      1. Kappa between LEAD procedure and DIGS ranged from 0.704 (major depression) to
      0.825 (bipolar I disorder). CONCLUSION: Most of the DSM-IV major psychiatric
      disorders can be assessed with acceptable to excellent reliability with the
      Spanish version of the DIGS interview. The Spanish version of DIGS showed an
      acceptable to excellent concurrent validity. Giving the good reliability and
      validity of Spanish version of DIGS it should be considered to identify
      psychiatric phenotypes for genetics studies.

PMID- 17188843
TI  - Body mass index and functioning in long-term schizophrenia. Results of the DSP
      project.
AB  - OBJECTIVE: The study evaluates the association of body mass index (BMI) with
      functioning in male and female patients with long-term schizophrenia. METHOD: 722
      long-term schizophrenia patients were interviewed three years after discharge
      from hospital. Their weight and height were recorded and data on their
      background, illness history, psychosocial functioning (Global Assessment Scale;
      GAS), health behaviour, daily doses of neuroleptics, and psychiatric symptoms
      were collected. RESULTS: BMI correlated significantly with GAS scores in male
      (r=0.202, p=0.000) but not in female patients. In male patients, BMI associated
      significantly (p=0.005) with GAS scores even when the effects of psychiatric
      symptoms and other confounding variables were taken into account. CONCLUSIONS: In
      male but not in female long-term patients with schizophrenia, low BMI associates
      with poor functioning. It is suggested that among male schizophrenia patients,
      low BMI may be an indicator of poor functioning.

PMID- 17188844
TI  - Trauma and defense style as response predictors of pharmacological treatment in
      panic patients.
AB  - BACKGROUND: As panic disorder (PD) has a chronic course, it is important to
      identify predictors that might be related to non-remission. The aim of this study
      is to verify whether history of trauma and defense style are predictors to
      pharmacological treatment response in PD patients. METHOD: The sample was
      composed by 47 PD patients according to DSM-IV who were treated with sertraline
      for 16 weeks. Evaluations were assessed by the C.G.I. (Clinical Global
      Impression), the Hamilton-Anxiety Scale, the Hamilton-Depression Scale, the Panic
      Inventory and the DSQ-40 (Defense Style Questionnaire) at baseline and after
      treatment. RESULTS: Full remission was observed in 61.7% of the sample. The
      predictors significantly associated with non-remission were: severity of PD
      (p=0.012), age of onset (p=0.02) and immature defenses (p=0.032). In addition,
      the history of trauma was associated with early onset of PD (p=0.043).
      CONCLUSION: Panic patients had as predictors of worse response to pharmacological
      treatment the early onset and the severity of PD symptoms as well as the use of
      immature defenses at baseline. This finding corroborates the relevance of the
      evaluation of factors that might affect the response so as to enable the
      development of appropriate treatment for each patient.

PMID- 17188845
TI  - Using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN 2.1) as a
      diagnostic interview providing dimensional measures: cross-national findings on
      the psychometric properties of psychopathology scales.
AB  - BACKGROUND: The Schedules for Clinical Assessment in Neuropsychiatry (SCAN) is a
      set of clinical assessment instruments developed under the auspices of WHO. In
      contrast to other structured diagnostic interviews, SCAN also provides
      possibilities for dimensional assessment of psychopathology. This paper reports
      cross-national findings on the psychometric properties of psychopathology scales
      derived from SCAN 2.1. METHODS: Within a randomized controlled trial, SCAN 2.1
      was used in Dresden (Germany), Michalovce (Slovak Republic), Prague (Czech
      Republic), and Wroclaw (Poland). Forty-seven items from Part I of SCAN 2.1,
      identified as qualifying for constructing dimensional measures, were, on the one
      hand, grouped according to their allocation to five specific SCAN 2.1 sections.
      On the other hand, principal component analyses were used to group the items
      according to their statistical relationship. To estimate the reliability of the
      scales, Cronbach's alpha was computed. To assess factor similarity across sites,
      Tucker's congruence coefficients were calculated. To appraise concurrent
      validity, mean scale scores were compared across different diagnostic groups.
      RESULTS: Reliability was qualified as moderate to substantial for all generated
      scales. Factor-solutions differed across sites. Differences in mean scores
      supported the assumption that the scales might possess, in addition to face
      validity, concurrent validity. CONCLUSIONS: This is the first cross-national
      study on the psychometric properties of psychopathology scales derived from SCAN
      2.1, and findings are very encouraging concerning its use as a dimensional
      measure. However, further studies are needed to substantiate implementation of
      the scales established.

PMID- 17188846
TI  - Prevalence and demography of transsexualism in Belgium.
AB  - AIM: The Belgian medical world has acknowledged the diagnosis of transsexualism
      and accepted Sex Reassignment Surgery (SRS) as one of the steps in the treatment
      of choice since 1985. This prevalence and demographic study analyses data on all
      Belgian individuals who have undergone SRS since that year. METHODS: All (188)
      plastic surgeons as well as all gender teams (Antwerp, Bruges, Ghent, and Liege)
      in Belgium were sent demographic questionnaires to be completed for each of their
      transsexual patients. RESULTS: The results show an overall prevalence of 1:12,900
      for male-to-female and 1:33,800 for female-to-male transsexuals in Belgium. In
      Wallonia (the French-speaking region of Belgium) the prevalence is significantly
      lower than in Flanders (the Dutch-speaking region) and in Brussels (the bilingual
      capital region). In the total Belgian population the male/female sex ratio is
      2.43:1, again with a substantial difference between Wallonia on the one hand and
      Flanders on the other. DISCUSSION AND CONCLUSION: While in Flanders and in
      Brussels the prevalence is comparable to that in other Western European
      countries, in Wallonia it is markedly lower. Transsexualism in Wallonia appears
      to be socially less acceptable: persons suffering from gender dysphoria in that
      part of Belgium encounter more problems accessing gender clinics and receiving
      treatment.

PMID- 17188847
TI  - Distribution of 1298A>C polymorphism of methylenetetrahydrofolate reductase gene
      in patients with bipolar disorder and schizophrenia.
AB  - We investigated the genotype frequency of methylenetetrahydrofolate reductase
      (MTHFR) 1298A>C polymorphism in the group of patients with bipolar disorder type
      I (BDI) (n=200) and schizophrenia (n=200) and in the control group (n=300). Odds
      ratio (OR) for patients with BD and schizophrenia in 1298CC homozygous state was
      3.768 (95% CI=1.752-8.104); P=0.0003; (P=0.0006 after Bonferroni correction) and
      2.694; (95% CI=1.207-6.013); P=0.0123 (P=0.0246 after Bonferroni correction),
      respectively. The stratification of patients based on gender revealed significant
      association of 1298CC genotype with female patients only with BDI (OR=7.293; 95%
      CI=2.017-26.363; P=0.0005). Our results confirm association of BD and
      schizophrenia with the 1p36.3 MTHFR locus and with the methyl group transfer
      using folate-dependent one-carbon pathway.

PMID- 17188848
TI  - Validity, reliability and objectivity of the family history method in psychiatry:
      a meta analysis.
AB  - BACKGROUND: The family history is a widely used method in psychiatry; but data on
      the method's objectivity, reliability and validity shows partly diverging
      results. METHOD: In October 2005, a Medline search was conducted that yielded 7
      studies regarding objectivity/reliability and 13 studies regarding validity.
      Results for six main groups of psychiatric diagnoses and any mental disorder were
      combined qualitatively for objectivity/reliability, and quantitatively for
      validity. RESULTS: Objectivity was generally high (kappa in the 0.80 range).
      Reliability was high for any mental disorder, schizophrenia, substance abuse and
      depression (kappa in the 0.70 range), and low or medium for anxiety (kappa
      between 0.30 and 0.50). Results on validity displayed an OR=148 for the family
      history for schizophrenia; OR=64 for mania/bipolar disorder; and OR's between 8
      and 194 for substance abuse, between 3 and 37 for depression, between 5 and 350
      for personality disorders, between 2.5 and 49 for anxiety, and between 2.4 and 9
      for any mental disorder. CONCLUSION: There is clear evidence that the family
      history provides results that are better than chance for all disorders examined.
      But variance among diagnostic groups and among studies is considerable.

PMID- 17188849
TI  - Endothelin-1 and angiotensin II contribute to BNP but not c-fos gene expression
      response to elevated load in isolated mice hearts.
AB  - The early events in the cardiac hypertrophic process induced by hemodynamic load
      include activation of B-type natriuretic peptide (BNP) and c-fos gene expression.
      However, it is unknown whether stretch acts directly or through local paracrine
      factors to trigger changes in cardiac gene expression. Herein we studied the
      involvement of endothelin-1 (ET-1) and angiotensin II (Ang II) in load-induced
      activation of left ventricular BNP and c-fos gene expression using an in vitro
      stretch model in isolated perfused adult mice hearts. Two-hour stretch induced by
      increasing coronary flow rate from 2 to 5 ml/min increased the expression of BNP
      and c-fos genes by 1.9- and 1.5-fold, respectively (P<0.001 and P<0.05). A mixed
      ET(A/B) receptor antagonist bosentan attenuated the BNP gene expression response
      to load by 58% (P<0.005). A similar 53% inhibition was observed with the
      selective ET(A) receptor blocker BQ-123 (P<0.05). Type 1 Ang II receptor
      antagonist CV-11974 decreased the activation of BNP gene expression by 50%
      (P<0.05). In contrast, the activation of c-fos gene expression was not inhibited
      by antagonists of ET(A/B) and AT(1) receptors. Our results show that ET-1 and Ang
      II play a key role in the induction of BNP, but not c-fos gene expression in
      response to load in intact adult murine hearts.

PMID- 17188850
TI  - Recombination and expression of classical swine fever virus (CSFV) structural
      protein E2 gene in Chlamydomonas reinhardtii chroloplasts.
AB  - The expression of classical swine fever virus (CSFV) structural protein E2 in
      different vectors, which has been shown to carry critical epitopes, has been
      established. Here, we reported a Chlamydomonas reinhardtii chloroplast expression
      vector, P64E2, containing classical swine fever virus structural protein E2 gene,
      which was constructed and transferred to C. reinhardtii by biolistic bombardment
      method. The transformants were identified by PCR, Southern blotting, Western
      blotting after selecting on resistant media. ELISA quantification assay showed
      that the expressed E2 protein accumulated up to 1.5-2% of the total soluble
      protein. The results of the study on the immunological activity indicated that
      the protein E2 expressed in C. reinhardtii chloroplasts could elicit animal
      bodies to produce antibodies against protein E2.

PMID- 17188851
TI  - An investigation into the usefulness of generalized regression neural network
      analysis in the development of level A in vitro-in vivo correlation.
AB  - Quantitative correlations between in vivo and in vitro data (IVIVC) reduce the
      number of human in vivo studies, thus decreasing the overall time and expenses
      necessary for the development of optimal drug product formulation. Although
      linear regression analysis represents the simplest relationship, it is recognized
      that IVIVC should not be limited to linear relationship. With regards to the
      implementation of non-linear IVIVC models and the ability of artificial neural
      network (ANN) computing to cope with non-linear relationships, the usefulness of
      ANN analysis in the development of IVIVC merits further evaluation. The present
      paper is an attempt to develop an IVIVC for model sustained release paracetamol
      matrix tablet formulations employing various correlation approaches based on
      linear and non-linear modeling of in vitro and in vivo data. Currently accepted
      compendial methodology was compared with the alternative approaches, involving
      general mixed effects model and generalized regression neural network (GRNN)
      analysis, in order to evaluate their usefulness for predicting the in vivo
      behavior of drug products. Although based on analogous approaches, data generated
      by GRNN were closer to those observed in vivo, leading to the higher level of
      IVIVC than obtained by convolution. It can be assumed that GRNN analysis was able
      to generalize complex relations between the output and input parameters and could
      account for the differences in drug release kinetics observed under various
      conditions in vitro, thus offering potential as a reliable and robust estimate of
      drug products in vivo behavior.

PMID- 17188852
TI  - [Metabolism of potassium in preterm infants].
AB  - During the first days of life, hyperkalemia can affect 30 to 60% of very low
      birth weight infants free of acute renal insufficiency (i.e. nonoliguric
      hyperkalemia). The place of the kidney in the regulation of the potassium
      homeostasis of VLBW remains badly specified. OBJECTIVE: To evaluate the rate and
      the mechanisms of hyperkalemia in infants born at less than 32 weeks' gestation.
      METHODS: A prospective study was conducted in 33 preterm infants (BW=1289+/-382
      g; GA=28.8+/-1.7 weeks). Fifteen consecutive 8-hour urine collections were
      performed for each infant from the 8th hour of life (495 periods). A plasma
      sample was obtained at the end of each urine collection. Sodium, potassium and
      creatinine were measured in urine and blood samples as often as possible.
      RESULTS: Plasma potassium concentrations varied significantly over the 15
      successive periods with an initial value (P1) of 4.55+/-0.80 mmol/l, a peak on P3
      (4.94+/-0.81 mmol/l) and the lowest value on P13 (3.88+/-0.42 mmol/l).
      Hyperkalemia (plasma potassium>6.0 mmol/l) was observed in 4 infants (12%) and in
      1.2% of the periods. The cumulative potassium balance (output-input) was negative
      over the first 7 periods (-1.97 mmol/kg), and afterwards became positive (from P8
      to P15:+1.57 mmol/kg). Over the first 3 days, plasma potassium concentrations
      were positively correlated (p<0.01) with urinary excretion of potassium,
      clearance of potassium, fractional excretion of potassium, and negatively with
      endogenous creatinine clearance. CONCLUSION: In the first days of life, very low
      birth weight infants present an increase in kalemia associated with a negative
      potassium balance indicating a intracellular to extracellular potassium shift
      rather than a lower renal potassium excretion.

PMID- 17188853
TI  - Interval training compared with continuous training in patients with COPD.
AB  - The aim of this study was to compare the effects of interval training (3-min
      intervals) with continuous training on peak exercise capacity (W peak),
      physiological response, functional capacity, dyspnoea, mental health and health
      related quality of life (HRQoL) in patients with moderate or severe COPD. Sixty
      patients exercised twice weekly for 16 weeks after randomisation to interval- or
      continuous training. Target intensity was 80% of baseline W peak in the interval
      group (I-group) and 65% in the continuous group (C-group). Patients were tested
      by spirometry, ergometer cycle test, cardiopulmonary test and a 12 min walk test.
      Dyspnoea was measured by the dyspnoea scale from Chronic Obstructive Disease
      Questionnaire (CRDQ), mental health by Hospital Anxiety and Depression scale
      (HAD) and HRQoL by the Medical Outcomes Survey Short Form 36 (SF-36). After
      training, W peak, peak oxygen uptake (VO(2) peak) and exhaled carbon dioxide
      (VCO(2) peak) increased significantly in both groups, no significant differences
      between the groups. Minute ventilation (V(E) peak) increased only in the C-group.
      At identical work rates (isotime) VO(2), VCO(2) and V(E) were significantly more
      decreased in the I-group than in the C-group (p<0.05). Functional capacity,
      dyspnoea, mental health, and HRQoL improved significantly in both groups, no
      difference between the groups. Interval training and continuous training were
      equally potent in improving peak exercise capacity, functional exercise capacity,
      dyspnoea, mental health and HRQoL in patients with moderate or severe COPD. At
      isotime, the physiological response to training differed between the groups, in
      favour of the interval training.

PMID- 17188854
TI  - Factors affecting adherence to asthma treatment in an international cohort of
      young and middle-aged adults.
AB  - BACKGROUND: A major reason of the poor control of asthma is that patients fail to
      adhere to their treatment. The aim of the study was to identify factors affecting
      changes in asthma treatment adherence in an international cohort. METHODS: A
      follow-up study was carried out by means of a structured clinical interview in
      971 subjects with asthma from 12 countries who participated in both the European
      Community Respiratory Health Survey: ECRHS-I (1990-94) and ECRHS-II (1998-2002).
      Subjects were considered adherent if they reported they normally took all the
      prescribed drugs. A logistic model was used to study the adjusted effect of the
      determinants. RESULTS: The net change in adherence to anti-asthmatic treatment
      per 10 years of follow-up was -2% (95% CI: -9.5, 5.5), 7.5% (-2.6, 17.6), 15.0%
      (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean,
      Continental and extra-European areas. Among the 428 non-adherent subjects in
      ECRHS-I, having regular consultations with health care professionals was the
      strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08-10.17). Among
      the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly
      predicted a persistence of adherence (OR 2.04; 95% CI: 1.11-3.75). No effect of
      gender, age, duration of the disease, smoking habit and educational level was
      observed. CONCLUSIONS: Our findings highlight the key role of doctors and nurses
      in educating and regularly reviewing the patients and support the efforts for an
      improvement of clinical communication.

PMID- 17188856
TI  - Bioelectrocatalytic application of titania nanotube array for molecule detection.
AB  - A bioelectrocatalysis system based on titania nanotube electrode has been
      developed for the quantitative detection application. Highly ordered titania
      nanotube array with inner diameter of 60 nm and total length of 540 nm was formed
      by anodizing titanium foils. The functionalization modification was achieved by
      embedding glucose oxidases inside tubule channels and electropolymerizing pyrrole
      for interfacial immobilization. Morphology and microstructure characterization,
      electrochemical properties and bioelectrocatalytic reactivities of this composite
      were fully investigated. The direct detection of hydrogen peroxide by
      electrocatalytic reduction reaction was fulfilled on pure titania nanotube array
      with a detection limit up to 2.0 x 10(-4)mM. A biosensor based on the glucose
      oxidase-titania/titanium electrode was constructed for amperometric detection and
      quantitative determination of glucose in a phosphate buffer solution (pH 6.8)
      under a potentiostatic condition (-0.4V versus SCE). The resulting glucose
      biosensor showed an excellent performance with a response time below 5.6s and a
      detection limit of 2.0 x 10(-3)mM. The corresponding detection sensitivity was
      45.5 microA mM(-1)cm(-2). A good operational reliability was also achieved with
      relative standard deviations below 3.0%. This novel biosensor exhibited quite
      high response sensitivity and low detection limit for potential applications.

PMID- 17188857
TI  - Template synthesis of highly ordered Prussian blue array and its application to
      the glucose biosensing.
AB  - In this paper, we propose a strategy to form nanoelectrode arrays by
      electrochemical deposition of the Prussian blue (PB) through highly ordered
      porous anodic alumina (PAA) membrane. The structure and morphology of the
      nanoarrays were characterized by scanning electron microscopy (SEM). As the
      highly ordered PB arrays can behave as an ensemble of closely spaced but isolated
      nanoelectrodes, the nanostructured PB arrays are successfully applied to improve
      the analytical performances of glucose by electrocatalytic reduction
      enzymatically liberated H(2)O(2). The resulting PB based nanoelectrode arrays
      show a wide linear calibration range over three orders of magnitude of glucose
      concentrations (5.0 x 10(-6) to 8.0 x 10(-3)M) and a low detection limit of 1
      microM. Moreover, the biosensor exhibits other good characteristics, such as
      short response time, high selectivity, excellent operation stability. In
      addition, effects of the glucose oxidase (GOx) loading, applied potential and pH
      on the biosensor performance were also discussed.

PMID- 17188855
TI  - To step or not to step? How biochemistry and mechanics influence processivity in
      Kinesin and Eg5.
AB  - Conventional kinesin and Eg5 are essential nanoscale motor proteins. Single
      molecule and presteady-state kinetic experiments indicate that both motors use
      similar strategies to generate movement along microtubules, despite having
      distinctly different in vivo functions. Single molecules of kinesin, a long
      distance cargo transporter, are highly processive, binding the microtubule and
      taking 100 or more sequential steps at velocities of up to 700 nm/s before
      dissociating, whereas Eg5, a motor active in mitotic spindle assembly, is also
      processive, but takes fewer steps at a slower rate. By dissecting the structural,
      biochemical and mechanical features of these proteins, we hope to learn how
      kinesin and Eg5 are optimized for their specific biological tasks, while gaining
      insight into how biochemical energy is converted into mechanical work.

PMID- 17188858
TI  - Detection of early renal transplant rejection by minimally-invasive monitoring of
      impedance variability.
AB  - BACKGROUND: Allograft rejection that occurs after renal transplants is identified
      by surveillance biopsies or by abnormal laboratory and/or hemodynamic data. The
      latter are insensitive markers of rejection that may not appear until significant
      histologic damage has already occurred. Therefore, a sensitive and specific non
      invasive method of detecting early rejection of transplanted solid organs is
      needed. METHOD: A single canine renal allograft was implanted followed by
      bilateral nephrectomy. Bipolar pacing electrodes were implanted at each end of
      the transplanted kidney. A second set of electrodes was implanted in the liver,
      which served as a non-rejecting normal organ. Electrodes were connected to an
      implantable sensor placed in the subcutaneous tissue. Electrical tissue impedance
      levels were telemetrically downloaded daily. The clinical status of the
      transplanted organ was monitored by following the blood urea nitrogen and serum
      creatinine levels, urine output, and clinical appearance. After tissue impedance
      levels had stabilized, all immunosuppressants were abruptly discontinued.
      Clinical signs of rejection were then observed after a few days. RESULTS:
      Rejection was accompanied by changes in electrical impedance of the implanted
      organ. These changes, when observed, occurred 1-5 days before clinical signs of
      rejection appeared. CONCLUSION: Analyses of these data suggest that development
      of a minimally-invasive high-confidence sensor of early rejection of solid organ
      transplants is feasible.

PMID- 17188859
TI  - Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion.
AB  - Onion intake might reduce the risk of colorectal cancer, according to
      epidemiology. However, Femia showed in 2003 that diets with a 20% onion intake
      increase carcinogenesis in rats. We speculated this dose was too high. Prevention
      of initiation was thus tested in 60 rats given a 5% dried onion diet or AIN76
      diet, and initiated 12 days later with azoxymethane (AOM, 1x20 mg/kg i.p.), 2
      amino-3-methylimidazo[4,5-f]quinoline (IQ, 2x200 mg/kg p.o.), or N-nitroso-N
      methylurea (2x50 mg/kg p.o.). Prevention of promotion was tested in 38 rats given
      AOM, then randomised to: AIN76 diet; 5% onion diet; phytochemicals diet
      (supplemented with propyl-disulfide, quercetine-glycosides and oligofructose); 1%
      pluronic F68 diet (a potent chemopreventive PEG-like block-polymer, used as a
      positive control). Aberrant crypt foci (ACF) were scored 30 days (initiation) or
      100 days (promotion) after carcinogen injection. The onion diet given during
      initiation reduced the number of AOM-induced ACF (60 versus 86, p=0.03), and the
      size of IQ-induced ACF (1.33 versus 1.97, p=0.02). Given post-initiation, the
      onion diet reduced the number of ACF (34 versus 59, p=0.008) and of large ACF (6
      versus 15, p=0.02). Phytochemicals diet and pluronic diet reduced ACF growth
      similarly. Data show that a 5% onion diet reduced carcinogenesis during
      initiation and promotion stages, and suggest this chemoprevention is due to known
      phytochemicals.

PMID- 17188860
TI  - Synthesis and SAR of 3,5-diamino-piperidine derivatives: novel antibacterial
      translation inhibitors as aminoglycoside mimetics.
AB  - Aminoglycoside antibiotics target an internal RNA loop within the bacterial
      ribosomal decoding site. Here, we describe the synthesis and SAR of novel 3,5
      diamino-piperidine derivatives as aminoglycoside mimetics, and show they act as
      inhibitors of bacterial translation and growth.

PMID- 17188861
TI  - A molecular modeling analysis of novel non-hydroxamate inhibitors of TACE.
AB  - Recently, an X-ray co-crystal structure of our hydroxamate inhibitor IK682 and
      TACE [Niu, X.; Umland, S.; Ingram, R.; Beyer, B. M.; Liu, Y.-H.; Sun, J.;
      Lundell, D.; Orth, P. Arch. Biochem. Biophys. 2006, 451, 43-50] was published
      that explicitly shows the orientation of the hydroxamate and the TACE-selective 4
      [(2-methyl-4-quinolinyl)methoxy]phenyl P1' group in the S1' and S3' sites. The
      preceding paper described a novel series of potent and TACE-selective hydantoins
      and we previously described pyrimidinetrione (barbiturate) inhibitors of TACE,
      both of which contain the same P1' group as IK682. Using this TACE-selective P1'
      group as an anchor, stereochemical and conformational constraints in the
      inhibitors, and restrictions to the active site Zn coordination geometry, we
      developed a highly plausible and predictive pharmacophore model that rationalizes
      the observed TACE activity of all three inhibitors.

PMID- 17188862
TI  - Inhibition of Src kinase activity by 7-ethynyl-4-phenylamino-3
      quinolinecarbonitriles: identification of SKS-927.
AB  - Of a series of 7-ethynyl-3-quinolinecarbonitriles, the most potent Src inhibitory
      activity was observed with 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[4
      (4-methylpiperazin-1-yl)but-1-ynyl]-3-quinolinecarbonitrile (SKS-927). Variation
      of the solubilizing amine tail or removal of the methoxy group from either C-6 of
      the quinoline core or C-5 of the aniline headpiece led to reduced activity.

PMID- 17188863
TI  - Discovery of novel hydantoins as selective non-hydroxamate inhibitors of tumor
      necrosis factor-alpha converting enzyme (TACE).
AB  - A series of novel hydantoins was designed and synthesized as structural
      alternatives to hydroxamate inhibitors of TACE. 5-Mono- and di-substituted
      hydantoins exhibited activity with IC50 values of 11-60 nM against porcine TACE
      in vitro and excellent selectivity against other MMPs.

PMID- 17188864
TI  - Pharmacophoric features of Pseudomonas aeruginosa deacetylase LpxC inhibitors: an
      electronic and structural analysis.
AB  - Various electronic properties of structurally diverse synthetic LpxC inhibitors
      containing oxazoline, aroylserine and thiazoline rings were calculated and
      correlated with biological activity. These electronic features include the
      magnitude and locations of 3-dimensional molecular electrostatic potentials,
      hydrogen bond acceptor/donor density, lowest unoccupied molecular orbital, and
      highest occupied molecular orbital. Strong correlation of these stereo-electronic
      properties with LpxC inhibitory potency reveals the potential pharmacophoric
      features of specific LpxC inhibitors. Thus, these pharmacophoric features of LpxC
      inhibitors based on electronic and surface analysis could be successfully
      exploited for designing more potent LpxC inhibitors.

PMID- 17188865
TI  - Synthesis and antitubercular activity of quaternized promazine and promethazine
      derivatives.
AB  - Quaternized chlorpromazine, triflupromazine, and promethazine derivatives were
      synthesized and examined as antitubercular agents against both actively growing
      and non-replicating Mycobacterium tuberculosis H37Rv. Impressively, several
      compounds inhibited non-replicating M. tuberculosis at concentrations equal to or
      double their MICs against the actively growing strain. All active compounds were
      non-toxic toward Vero cells (IC50 > 128 microM). N-Allylchlorpromazinium bromide
      was only weakly antitubercular, but replacing allyl with benzyl or substituted
      benzyl improved potency. An electron-withdrawing substituent on the phenothiazine
      ring was also essential. Branching at the carbon chain decreased antitubercular
      activity. The optimum antitubercular structures possessed N-(4- or 3
      chlorobenzyl) substitution on triflupromazine.

PMID- 17188866
TI  - Constrained 7-fluorocarboxychromone-4-aminopiperidine based Melanin-concentrating
      hormone receptor 1 antagonists: the effects of chirality on substituted indan-1
      ylamines.
AB  - The incorporation of constrained tertiary amines into an existing class of N
      benzyl-4-aminopiperidinyl chromone-based MCHr1 antagonists led to the
      identification of a series of chiral racemic compounds that displayed good to
      excellent functional potency, binding affinity, and selectivity over the hERG
      channel. Further separation of two distinct chiral racemic compounds into their
      corresponding pairs of enantiomers revealed a considerable selectivity for MCHr1
      for one configuration, in addition to a striking difference in oral exposure
      between one pair of enantiomers in diet-induced obese mice. Oral administration
      of the most potent compound in this class in the same animal model led to
      significant reduction of fat mass in a semi-chronic model for weight loss.

PMID- 17188867
TI  - 1,5-Benzodioxepin derivatives as a novel class of muscarinic M3 receptor
      antagonists.
AB  - The structure-activity relationships of novel 1,5-benzodioxepin derivatives as
      muscarinic M(1)-M(3) receptor antagonists are reported. Some of these compounds
      were found to possess high binding affinity for the muscarinic M(3) receptor and
      potent effect on rhythmic increase in bladder pressure in unanesthetized rats
      following oral administration. These compounds displayed selectivity for the
      bladder over the salivary gland.

PMID- 17188868
TI  - Structural simplification of bioactive natural products with multicomponent
      synthesis: dihydropyridopyrazole analogues of podophyllotoxin.
AB  - A three-component condensation of 5-amino-3-methylpyrazole, tetronic acid, and
      various aromatic, heteroaromatic, and aliphatic aldehydes leads to the formation
      of dihydropyridopyrazole analogues of a cytotoxic lignan podophyllotoxin. This
      new heterocyclic scaffold-based library allows a drastic reduction of the
      structural complexity of the natural product with the retention of its potent
      cytotoxic properties. Similarly to podophyllotoxin, the presented analogues
      induce apoptosis in Jurkat cells.

PMID- 17188869
TI  - Thienopyridine urea inhibitors of KDR kinase.
AB  - A series of substituted thienopyridine ureas was prepared and evaluated for
      enzymatic and cellular inhibition of KDR kinase activity. Several of these
      analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and
      cellular assays. Further characterization of inhibitor 2 indicated that this
      analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an
      estradiol-induced mouse uterine edema model.

PMID- 17188870
TI  - Dopamine/serotonin receptor ligands. Part 15: Oxygenation of the benz-indolo
      azecine LE 300 leads to novel subnanomolar dopamine D1/D5 antagonists.
AB  - Relying on the high affinities of the benz-indolo-azecine LE 300 (1) and the
      hydroxylated dibenz-azecine LE 404 (2b) for the D1/D5 receptor subtypes, we
      synthesized methoxylated, hydroxylated and an indole-N methylated derivatives of
      1 (Fig. 1). Hydroxylation of azecine derivatives is beneficial with regard to the
      affinities and selectivities for all the dopamine receptor subtypes. The
      'serotonin-derived' 3-oxygenated target compounds but not the 11-oxygenated
      analogues were superior to the unsubstituted LE 300. 11-Methoxy-7,14-dimethyl
      6,7,8,9,14,15-hexahydro-5H-indolo[3,2-f][3]benzazecine (3e) was found to be the
      most potent antagonist at D2/D3/D4 and D5 receptor subtypes (Ki for D5 = 0.23
      nmol) of all known benz-indolo-azecines.

PMID- 17188871
TI  - In vitro selection of RNA aptamer against Escherichia coli release factor 1.
AB  - A pool of 84-nt RNAs containing a randomized sequence of 50 nt was selected
      against gel-immobilized Escherichia coli release factor 1 (RF-1) responsible for
      translation termination at amber (UAG) stop codon. The strongest aptamer (class
      II-1) obtained from 43 clones bound to RF-1, but not to UAA/UGA-targeting RF-2,
      with Kd = 30+/-6 nM (SPR). A couple of unpaired hairpin domains in the aptamer
      were suggested as the sites of attachment of RF-1. By binding to and hence
      inhibiting the action of RF-1 specifically or bio-orthogonally, aptamer class II
      1 enhanced the amber suppression efficiency in the presence of an anticodon
      adjusted (CUA) suppressor tRNA without practically damaging the protein
      translation machinery of the cell-free extract of E. coli, as confirmed by the
      translation of amber-mutated (gfp(amber141) or gfp(amber178)) and wild-type
      (gfp(wild)) genes of GFP.

PMID- 17188873
TI  - ortho-Substituted azoles as selective and dual inhibitors of VEGF receptors 1 and
      2.
AB  - We have developed a series of novel potent ortho-substituted azole derivatives
      active against kinases VEGFR-1 and VEGFR-2. Both specific and dual ATP
      competitive inhibitors of VEGFR-2 were identified. Kinase activity and
      selectivity could be controlled by varying the arylamido substituents at the
      azole ring. The most specific molecule (17) displayed > 10-fold selectivity for
      VEGFR-2 over VEGFR-1. Compound activities in enzymatic and cell-based assays were
      in the range of activities for reported clinical and development candidates (IC50
      < 100 nM), including Novartis' PTK787 (Vatalanib). High permeability of active
      compounds across the Caco-2 cell monolayer (> 30x10(-5) cm/min) is indicative of
      their potential for intestinal absorption upon oral administration.

PMID- 17188872
TI  - A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition
      of HIV integrase and anti-HIV activity.
AB  - We have synthesized novel phosphonic acid analogues of beta-diketo acids.
      Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was
      an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2
      had lower anti-HIV activity than 1, but was more active and less toxic than the
      phosphonic acid analogue of L-708906. These isosteric compounds represent the
      first examples of beta-diketo phosphonic acids of structural, synthetic, and
      antiviral interest.

PMID- 17188874
TI  - How many nurses are enough?

PMID- 17188876
TI  - Statistical design of unicompartmental tibial implants and comparison with
      current devices.
AB  - This study defines, in the context of unicompartmental tibial replacement, the
      medial and lateral resection surfaces of 34 tibiae at a depth of 5 mm below the
      articular surface. Using statistical techniques, three optimal theoretical size
      and shape unicompartmental tibial designs, (i) implants of consistent shape in
      varying size (ii) implants symmetric about their ML axis; (iii) implants of
      varying size and shape, were constructed to best fit the population. Two
      currently available commercial implants, the Preservation Uni System (DePuy
      Orthopaedics Inc., Warsaw, IN) and the LCS Uni System (DePuy Orthopaedics Inc.,
      Warsaw, IN), which were similar to types (i) and (ii) respectively, of the
      theoretical designs, were also included in the analysis. All implants, commercial
      and theoretical, were compared with one another to determine which implant
      designs gave the best cortical bone coverage on both the medial and lateral
      compartments. Of the commercial implants, the type (i) design fitted best, with
      an average of 67% of the implant edge lying on cortical bone, compared with 57%
      for the type (ii) implants. Of the theoretical implants, 72%, 67% and 76% of the
      implant edge lay on cortical bone for types (i), (ii) and (iii) designs,
      respectively, indicating that there is room for improvement in current implant
      designs to achieve better coverage in both the medial and lateral compartments
      combined.

PMID- 17188878
TI  - A simple, yet highly accurate, QSAR model captures the complement inhibitory
      activity of compstatin.
AB  - Compstatin is a 13-residue cyclic peptide inhibitor of complement activation that
      was originally identified through phage-mediated presentation of a peptide
      library to C3b. Recent efforts to improve its activity have led to a rich dataset
      of complement analogs, with the most active analog being approximately 260 times
      more active than the parent compstatin. In the present work, a highly transparent
      quantitative structure-activity relationship model (Radj2=0.89) with four
      parameters is presented that captures important physico-chemical and geometrical
      properties of the analog molecules with regard to activity. The number of
      aromatic bonds and hydrophobicity of the fourth residue of compstatin correlated
      strongly with activity. Also important were the hydrophobic patch size near the
      disulfide bond and the solvent-accessible surface area occupied by nitrogen atoms
      of basic amino acid residues.

PMID- 17188877
TI  - Neoligamentization process of BTPB used for ACL graft: histological evaluation
      from 6 months to 10 years.
AB  - Following anterior cruciate ligament (ACL) reconstruction with the middle third
      part patellar tendon, the graft undergoes histological rearrangement due to
      biomechanical action, which transforms it into a structure similar to the normal
      ACL. The purpose of our study was to make a qualitative and quantitative
      histological evaluation, by transmission electron microscopy (TEM), of the
      neoligamentization process of a bone-patellar tendon-bone (BTPB) graft used as
      pro-ACL at different follow-up times. We analysed the ultrastructure of collagen
      fibrils by focusing on their size and distribution with respect to a normal
      patellar tendon and a normal ACL used as controls. Our results showed that up to
      24 months follow-up, progressive ultrastructural changes towards the normal ACL
      were observed. At longer times after surgery (48 and 120 months) no further
      changes were evident and the ultrastructure showed a marked reduction in large
      fibrils, which was typical of the control patellar tendon, and a significant
      increase in small fibrils. The ultrastructure seemed to combine fibrils from two
      different morphological units. The BPTB graft used as ACL underwent a
      transformation process for up to two years. After that period the transformation
      ceased and for ten years failed to reach the ultrastructural aspect of a normal
      ACL. However, from an architectural point of view the graft was slowly
      transformed into a structure similar to ACL with respect to the different
      mechanical stresses the ligament has to sustain.

PMID- 17188879
TI  - Endomorphin-1 analogs with enhanced metabolic stability and systemic analgesic
      activity: design, synthesis, and pharmacological characterization.
AB  - We synthesized four new analogs of endomorphin-1 by systematic chemical
      modifications. To identify the best possible drug candidates for clinical pain
      management and to investigate the potential contribution of these alterations to
      the biological activity, their pharmacological properties were determined. All of
      the analogs showed significantly enhanced metabolic stability. The fact that
      centrally mediated analgesia following peripheral administration was observed
      with one of the analogs suggested the approach design undertaken here had
      validity in the development of endomorphin-1 as a successful opioid drug for the
      clinic.

PMID- 17188880
TI  - WDS versus silicon drift detector EDS: a case report for the comparison of
      quantitative chemical analyses of natural silicate minerals.
AB  - Electron probe microanalysis (EPMA) is an essential analytical approach to
      determine elemental concentrations of various solid specimens quantitatively in
      mineralogical, petrological and materials research. Either wavelength dispersive
      X-ray (WDS) or energy dispersive X-ray (EDS) spectrometric techniques can collect
      the characteristic X-rays generated from each element in the specimen by an
      incident electron beam in order to define chemical constituents. Although WDS has
      been the preferred technique because of its higher spectral resolution and
      ability to detect trace elements, new generation EDS systems with silicon drift
      detectors (SDD), equipped with thin windows and integrated digital processing
      electronics, are claimed to approach the WDS throughput. In this study, we
      compared the analytical capability of a SDD EDS system with respect to WDS
      equipped systems on natural silicate minerals. For this purpose, natural rock
      samples, in which the silicate minerals present had already been analysed by
      various WDS systems, were chosen to compare these results with the ones acquired
      with a SDD EDS system. SDD EDS yielded satisfactory results for major elements
      (Na, Mg, Al, Si, K, Ca, Ti, Mn and Fe) compared with the results of the same
      minerals obtained by various WDS systems.

PMID- 17188881
TI  - The intensity of immunogold labeling of deplasticized acrylic sections compared
      to deplasticized epoxy sections-Theoretical deductions and experimental data.
AB  - The purpose of this study was to compare the level of immunogold labeling of
      deplasticized acrylic sections and deplasticized epoxy sections. Pure protein
      gels of IgG, albumin and thyroglobulin were produced by glutaraldehyde fixation
      and embedded in non-crosslinked acrylic resin (Technovit 9100) and epoxy resin
      (Epon 812), respectively. Ultrathin sections of acrylic and epoxy resin were
      separately deplasticized in 2-methoxyethyl acetate (MEA) and sodium ethoxide.
      Quantitative immunogold labeling was performed with anti-IgG, anti-albumin and
      anti-thyroglobulin antibodies on sections of the corresponding protein gels. For
      all antibodies tested, the intensity of labeling for deplasticized acrylic
      sections was significantly higher (two to four times) than for the corresponding
      deplasticized epoxy sections. The results fit with a theoretically deduced
      relation: the quotient of the labeling of two deplasticized sections of different
      resins is equivalent to the square root of the quotient of the labeling of the
      similar sections not exposed to any kind of pre-treatment. The practical
      significance of the results is that immunolabeling of deplasticized non
      crosslinked acrylic resin results in more intense immunogold labeling than
      deplasticized epoxy sections. Deplasticizing is most useful when the requirements
      for ultrastructural preservation according to conventional criteria are moderate.
      Our theoretically deduced results also indicate that deplasticized Technovit (or
      other non-crosslinked acrylic resins) sections will be significantly better
      suited for immunolabeling at the light microscopic level than deplasticized epoxy
      sections.

PMID- 17188882
TI  - Osteopontin is elevated in Parkinson's disease and its absence leads to reduced
      neurodegeneration in the MPTP model.
AB  - In the pathogenesis of Parkinson's disease (PD), oxidative and nitrosative
      stress, apoptosis, mitochondrial dysfunction, and excitotoxicity are involved,
      i.e., processes in which osteopontin (OPN) may also play a role. We have studied
      in PD patients serum and cerebrospinal fluid (CSF) concentrations of OPN, its
      immunohistochemical presence in substantia nigra (SN) and tested in OPN-null mice
      the impact of this protein on MPTP-induced neurodegeneration. PD was accompanied
      by increased OPN levels in the body fluids. Higher serum levels were associated
      with more severe motor symptoms. CSF levels were positively associated with
      concomitant dementia and negatively associated with dopaminergic treatment. In
      human SN, OPN was expressed in neurons, in their Lewy bodies and in microglia.
      Loss of tyrosine-hydroxylase-positive cells in the SN and of dopaminergic fibers
      in the striatum was reduced 3 weeks after MPTP intoxication in OPN-null mice.
      These data suggest that OPN is involved in PD-associated neurodegeneration.

PMID- 17188883
TI  - Pretreatment with aminophylline reduces release of Troponin I and neutrophil
      activation in the myocardium of patients undergoing cardioplegic arrest.
AB  - OBJECTIVE: Cardioplegic arrest and subsequent reperfusion results in myocardial
      injury partly related to local inflammation in the heart. It has been proven that
      aminophylline has numerous anti-inflammatory effects. This study has been
      designed to evaluate the effects of aminophylline used as a cardioprotective
      agent for patients undergoing cardiopulmonary bypass (CPB) for valve replacement.
      METHODS: Thirty patients undergoing elective valve replacement were randomized to
      receive either aminophylline (n=15), or normal saline (control n=15).
      Administration of aminophylline (5mg/kg) was injected intravenously after
      induction of anesthesia. The cardiac Troponin I (cTnI), myocardial
      myeloperoxidase (MPO) activity, atrial cyclic AMP, and a coronary sinus
      neutrophil count were measured before and after cardioplegic arrest. RESULTS:
      There were no differences between the two groups with regard to clinical
      variables. The cTnI concentration increased significantly after aortic declamping
      in both groups. However, it was significantly lower, 8h after aortic declamping,
      in aminophylline group (1.00+/-0.41 vs 2.37+/-1.35 ng/ml p=0.038). The atrial
      cAMP was significantly higher before aortic cross-clamping in aminophylline group
      (42.5+/-6.7 pmol/g tissue vs 30.6+/-12.4 pmol/g tissue p=0.04). In addition, we
      found that the aminophylline group had a significantly lower MPO after
      reperfusion (1.50+/-0.58 U/g tissue vs 0.86+/-0.24 U/g tissue p=0.003), and a
      significantly lower neutrophil count 30 min after aortic declamping (0.68+/
      0.11x10(3) cell/ml vs 0.32+/-0.16x10(3) cell/ml, p=0.023). CONCLUSIONS:
      Pretreatment with intravenous aminophylline reduces the subclinical myocardial
      injury and neutrophil activation in patients undergoing CPB for valve
      replacement.

PMID- 17188884
TI  - Replacing cardiopulmonary bypass with extracorporeal membrane oxygenation in lung
      transplantation operations.
AB  - OBJECTIVE: Cardiopulmonary bypass (CPB) support is required in some lung
      transplantation (LTX) operations. CPB support and full-dose heparin increases the
      risks of bleeding and early graft dysfunction. We report our experiences of
      replacing CPB with heparin-bonded low-dose heparin extracorporeal membrane
      oxygenation (ECMO) support in LTX surgery. METHODS: From 2003 to 2005 forty-seven
      patients were transplanted. Thirty-seven LTX patients were retrospectively
      evaluated for this study (10 patients were excluded due to heart-lung-, lung
      kidney transplantation, LTX with bypass grafting, and ASD closure or emergency
      CPB support). Extracorporeal circulation support was necessary in 40% of the 37
      LTX patients due to severe primary or secondary pulmonary hypertension (P or
      SPHTN), right heart dysfunction, or hemodynamic instability. There were seven LTX
      procedures with CPB and eight implantations with ECMO support. CPB (high-dose
      heparin) and ECMO support (ACT 160-220 s) was always set up through femoral veno
      arterial canulation. All patients had limited access thoracotomies without
      transsection of the sternum. Normothermia was maintained in all patients. CPB
      patients: PPH 15%, COPD 15%, IPF with mean PAP>40 mmHg 70%. ECMO patients: PPH
      13%, COPD 13%, IPF with severe PAP pressure elevation 74%. RESULTS: In patients
      undergoing LTX for PPH, the ECMO support was directly extended into the post
      operative period. Packed red blood cell (PRBC) transfusion requirements during
      the operation and the first 24h were 13.25+/-1.6 PRBC units versus 5.1+/-2.8 PRBC
      units on CBP (p=0.02). Operative time was longer (p=0.11) in the ECMO LTX (451
      min+/-76 vs 346+/-140). The increased 90-day mortality rate of the ECMO patients
      showed a trend toward significance (p=0.056), which was related to infectious
      complications (3 vs 1 patient). Severe graft ischemia/reperfusion injury occurred
      in 9% in the CPB versus 13% in the ECMO group. The 1-year survival was
      significantly reduced in ECMO patients (p=0.004, log-rank test). CONCLUSIONS: The
      advantages of femoral canulation rather than conventional central connections in
      lung transplantation procedures led to an undisturbed operative field. A
      significantly higher blood product amount was required in ECMO patients, which
      might lead to increased infection and mortality rates. CPB, obviously, should
      remain the standard support technique if extracorporeal circulation is required
      in lung transplantation surgery.

PMID- 17188885
TI  - A phase II study of intrapleural immuno-chemotherapy, pleurectomy/decortication,
      radiotherapy, systemic chemotherapy and long-term sub-cutaneous IL-2 in stage II
      III malignant pleural mesothelioma.
AB  - OBJECTIVE: From therapeutic nihilism to extremely aggressive management, there is
      a wide range of possibilities in the treatment of malignant pleural mesothelioma
      (MPM). Unfortunately, there is little evidence as regards the best treatment to
      offer to the MPM patients. In 1999, we started a phase II study based on the
      multimodality treatment of stage II-III MPM, the results of which have been
      analysed and reported. METHODS: From 1999 to 2004, 49 patients with IMIG stage II
      III MPM underwent a multimodality treatment including: intrapleural pre-operative
      interleukin 2 (IL-2, 18x10(6) UI/day per 3 days), pleurectomy/decortication,
      intrapleural post-operative epidoxorubicin (25mg/m2 per 3 days), IL-2 (18x10(6)
      UI/day per 3 days), adjuvant radiotherapy (30Gy), systemic chemotherapy
      (cisplatin 80 mg/m2 day 1, gemcitabine 1250 mg/m2 day 1 and 8 up to 6 courses)
      and long-term sub-cutaneous IL-2 (3x10(6) UI/day 3 days per week). RESULTS: There
      were 41 males and 8 females with a median age of 61 years (range 41-77). All the
      patients had a diagnosis of MPM by thoracoscopy before inclusion. We did not
      experience any post-operative mortality. The histology was: 39 epitheliomorf, 6
      bifasic and 4 sarcomatous. According to the IMIG the post-operative staging was
      III in 40 cases and II in 9 cases. With a median follow-up of 59 months (range 14
      81) 13 patients are still alive and the median actuarial survival is 26 months
      (31 and 21 months for stage II and III, respectively). Only the Performance
      Status at the diagnosis affected survival significantly. CONCLUSIONS: The
      multimodality treatment we adopted for stage II-III MPM was feasible, well
      tolerated by most of the patients and produced a favourable outcome. New targeted
      therapies are awaited for further improvements in the treatment of this disease.

PMID- 17188886
TI  - Measured FEV1 in the first postoperative day, and not ppoFEV1, is the best
      predictor of cardio-respiratory morbidity after lung resection.
AB  - INTRODUCTION AND OBJECTIVE: There is a low correlation between predicted
      postoperative FEV1 (ppoFEV1) and FEV1 measured the days after pulmonary
      resection, when most complications are developed. The hypothesis of this
      investigation is that ppoFEV1 does not predict postoperative morbidity in
      patients undergoing lung resection when immediate postoperative FEV1 is
      considered in the predictive model. METHODS: One hundred ninety-eight consecutive
      patients undergoing lobectomy or pneumonectomy were included in a prospective,
      multiinstitutional study. INDEPENDENT VARIABLES: age, body mass index, ppoFEV1,
      surgical approach (VATS or muscle-sparing thoracotomy), type of analgesia
      (epidural or intraveous), postoperative visual analogue pain score and FEV1
      measured the day after the operation. Target variable: occurrence of
      postoperative cardio-respiratory complications. Method of analysis:
      classification tree (CART) dividing the population at random in two subsets and
      developing a bootstrap set of 100 trees resampling training data. The relative
      importance of each variable and the accuracy of both initial and committee trees
      to predict the outcome were presented. RESULTS: One hundred seventy-seven
      lobectomies and 21 pneumonectomies were included. Overall cardio-respiratory
      morbidity was 22%. According to CART results, first day FEV1 was the most
      important variable to classify cases as primary splitter and as a surrogate of
      each primary splitter (100% importance). Patient age followed (51%) and ppoFEV1
      was third (43%) with a score similar to postoperative pain score (42%) and type
      of analgesia (36%). Sensitivity and specificity of the initial tree were,
      respectively, 0.5 and 0.7; values for committee tree were 0.5 sensitivity and 0.7
      specificity. CONCLUSION: Postoperative cardio-respiratory complications are more
      related to FEV1 measured in the first postoperative day than to ppoFEV1 value.

PMID- 17188887
TI  - Should intraperitoneal chemotherapy be considered as standard first-line
      treatment in advanced stage ovarian cancer?
AB  - Current standard therapy for patients with advanced stage epithelial ovarian
      cancer is cytoreductive surgery followed by combination chemotherapy with
      paclitaxel and carboplatin. Intraperitoneal (IP) chemotherapy has demonstrated
      improved outcome compared to standard intravenous treatment in three large
      randomized phase III trials and confirmed by Cochrane meta-analysis. Although
      compelling evidence suggests that IP therapy provides survival benefit in a
      selected group of ovarian cancer patients, it remains unclear which group of
      patients will really benefit from IP therapy, which is the optimal drug, dose and
      combination, and what is the real benefit of IP treatment alone. Other concerns
      about IP therapy are difficulties in completing the assigned treatment and
      management of its pattern of toxic side-effects. Today, IP chemotherapy has yet
      to gain a role as standard first-line treatment in advanced stage ovarian cancer.
      In the near future, efforts should aim at developing an effective IP regimen and
      research undertaken for a better understanding of the peritoneal environment.

PMID- 17188888
TI  - Cytokine gene expression in Walker 256: a comparison of variants A (aggressive)
      and AR (regressive).
AB  - Two variants of this Walker 256 tumor have been previously reported as Walker 256
      A and variant AR. The variant A has more aggressive property than variant AR and
      can induce systemic effects such as anorexia, sodium and water retention,
      followed by weight loss and death. The mechanisms involved in enhancing tumor
      regression and progression in this model are still incompletely understood. In
      the present study, serum and spleen mononuclear cells and tumor cells from
      animals inoculated with variants A and AR, were isolated to investigate the TGF
      beta, IL-12, IFN-gamma and TNF-alpha and relationship with anemia, weight of
      animals, weight of spleen, volume of tumor and osmotic fragility compared with
      controls inoculated with Ringer Lactate. Results demonstrate that the group
      inoculated with variant A, compared to variant AR, shows high levels of TGF-beta
      gene expression in both tumor tissue and spleen cells, no expression of IFN-gamma
      and a progressive and higher levels of IL-12 in tumor tissue without inflammatory
      infiltrate visualized by optical microscopy. These results suggest that the
      aggressively of variant A is relate to cytokine modulation, facilitating the
      growth and escape of tumor cells. Furthermore, IL-12 seems to be constitutively
      expressed in both tumor lineage A and AR.

PMID- 17188889
TI  - Calcium-dependent interactions of the human norepinephrine transporter with
      syntaxin 1A.
AB  - The norepinephrine (NE) transporter (NET) terminates noradrenergic signaling by
      clearing released NE at synapses. The activity of NET can be rapidly regulated by
      depolarization and receptor activation via Ca2+ and kinase/phosphatase-linked
      pathways. The SNARE protein syntaxin 1A (SYN1A) interacts with NET and influences
      transporter surface trafficking and catalytic activity. In this study, we
      establish a link between changes in intracellular Ca2+ and SYN1A/NET
      interactions. SYN1A influenced NE transport only in the presence of Ca2+ in brain
      cortical synaptosomes. Although NET/SYN1A associations were sensitive to
      manipulations of Ca2+ in CHO cells, in vitro binding experiments using purified
      NET and SYN1A fusion proteins demonstrated a lack of direct Ca2+ sensitivity.
      Disruption of NET/SYN1A interaction abolished inhibition of NE transport by
      phorbol ester (PMA) to activate protein kinase C (PKC), but had no effect on
      transport inhibition by the Ca2+ calmodulin kinase (CaMK) inhibitor KN93.
      Furthermore, PMA enhanced Ca2+-dependent modulation of NE transport in
      synaptosomes. Our data reveal roles for SYN1A in the Ca2+-dependent regulation of
      NET, likely reliant on regulation by PKC signaling, but independent of CaMK.

PMID- 17188891
TI  - A fluorogenic substrate as quantitative in vivo reporter to determine protein
      expression and folding of tobacco etch virus protease in Escherichia coli.
AB  - Quantitative and folding reporters are adequate tools to optimize recombinant
      protein expression in various host organisms, including Escherichia coli. To
      determine the yield of soluble active protease from the tobacco etch virus (TEV),
      we developed a single-molecule assay based on the fluorogenic substrate ANA-QS
      MCA. This substrate consists of a 10 amino acid peptide (ENLYFQSGTK) containing
      the proteolytic cleavage sequence of the TEV protease. The peptide works as a
      linker N-terminally tagged with a fluorescent donor group (7-Methoxycoumarin-4
      yl)acetyl (MCA) and C-terminally tagged with the acceptor group 5-Amino-2
      nitrobenzoic acid (ANA). Fluorescence can be observed after specific cleavage of
      the substrate at the Gln-Ser bond by active TEV protease. Purified His-tagged TEV
      protease was used for in vitro analysis. Through determination of proteolytic
      activity in living E. coli cells and through application of Confocal Laser
      Scanning-Microscopy we demonstrate that the peptide is well suited to in vivo
      expression analysis. This provides an effective tool to monitor the accumulation
      of active recombinant TEV protease in crude extracts and intact cells.

PMID- 17188890
TI  - Pro-NGF secreted by astrocytes promotes motor neuron cell death.
AB  - It is well established that motor neurons depend for their survival on many
      trophic factors. In this study, we show that the precursor form of NGF (pro-NGF)
      can induce the death of motor neurons via engagement of the p75 neurotrophin
      receptor. The pro-apoptotic activity was dependent upon the presence of sortilin,
      a p75 co-receptor expressed on motor neurons. One potential source of pro-NGF is
      reactive astrocytes, which up-regulate the levels of pro-NGF in response to
      peroxynitrite, an oxidant and producer of free radicals. Indeed, motor neuron
      viability was sensitive to conditioned media from cultured astrocytes treated
      with peroxynitrite and this effect could be reversed using a specific antibody
      against the pro-domain of pro-NGF. These results are consistent with a role for
      activated astrocytes and pro-NGF in the induction of motor neuron death and
      suggest a possible therapeutic target for the treatment of motor neuron disease.

PMID- 17188893
TI  - Assembly defects of desmin disease mutants carrying deletions in the alpha
      helical rod domain are rescued by wild type protein.
AB  - Most mutations of desmin that cause severe autosomal dominant forms of
      myofibrillar myopathy are point mutations and locate in the central alpha-helical
      coiled-coil rod domain. Recently, two in-frame deletions of one and three amino
      acids, respectively, in the alpha-helix have been described and discussed to
      drastically interfere with the architecture of the desmin dimer and possibly also
      the formation of tetramers and higher order complexes [Kaminska, A., Strelkov,
      S.V., Goudeau, B., Olive, M., Dagvadorj, A., Fidzianska, A., Simon-Casteras, M.,
      Shatunov, A., Dalakas, M.C., Ferrer, I., Kwiecinski, H., Vicart, P., Goldfarb,
      L.G., 2004. Small deletions disturb desmin architecture leading to breakdown of
      muscle cells and development of skeletal or cardioskeletal myopathy. Hum. Genet.
      114, 306-313.]. Therefore, it was proposed that they may poison intermediate
      filament (IF) assembly. We have now recombinantly synthesized both mutant
      proteins and subjected them to comprehensive in vitro assembly experiments. While
      exhibiting assembly defects when analyzed on their own, both one-to-one mixtures
      of the respective mutant protein with wild type desmin facilitated proper
      filament formation. Transient transfection studies complemented this fundamental
      finding by demonstrating that wild type desmin is also rescuing these assembly
      defects in vivo. In summary, our findings strongly question the previous
      hypothesis that it is assembly incompetence due to molecular rearrangements
      caused by the mutations, which triggers the development of disease. As an
      alternative, we propose that these mutations cause subtle age-dependent
      structural alterations of desmin IFs that eventually lead to disease.

PMID- 17188892
TI  - A thermally induced phase transition in a viral capsid transforms the hexamers,
      leaving the pentamers unchanged.
AB  - Scanning calorimetry combined with cryo-electron microscopy affords a powerful
      approach to investigating hierarchical interactions in multi-protein complexes.
      Calorimetry can detect the temperatures at which certain interactions are
      disrupted and cryo-EM can reveal the accompanying structural changes. The
      procapsid of bacteriophage HK97 (Prohead I) is a 450A-diameter shell composed of
      60 hexamers and 12 pentamers of gp5, organized with icosahedral symmetry. Gp5
      consists of the N-terminal Delta-domain (11kDa) and gp5* (31 kDa): gp5* forms the
      contiguous shell from which clusters of Delta-domains extend inwards. At neutral
      pH, Prohead I exhibits an endothermic transition at 53 degrees C with an enthalpy
      change of 14 kcal/mole (of gp5 monomer). We show that this transition is
      reversible. To capture its structural expression, we incubated Prohead I at 60
      degrees C followed by rapid freezing and, by cryo-EM, observed a capsid species
      10% larger than Prohead I. At 11A resolution, visible changes are confined to the
      gp5 hexamers. Their Delta-domain clusters have disappeared and are presumably
      disordered, either by unfolding or dispersal. The gp5* hexamer rings are thinned
      and flattened as they assume the conformation observed in Expansion Intermediate
      I, a transition state of the normal, proteolysis-induced, maturation pathway. We
      infer that, at ambient temperatures, the hexamer Delta-domains restrain their
      gp5* rings from switching to a lower free energy, EI-I-like, state; above 53
      degrees, this restraint is overcome. Pentamers, on the other hand, are more
      stably anchored and resist this thermal perturbation.

PMID- 17188894
TI  - The impact of computer display height and desk design on 3D posture during
      information technology work by young adults.
AB  - Computer display height and desk design to allow forearm support are two critical
      design features of workstations for information technology tasks. However there
      is currently no 3D description of head and neck posture with different computer
      display heights and no direct comparison to paper based information technology
      tasks. There is also inconsistent evidence on the effect of forearm support on
      posture and no evidence on whether these features interact. This study compared
      the 3D head, neck and upper limb postures of 18 male and 18 female young adults
      whilst working with different display and desk design conditions. There was no
      substantial interaction between display height and desk design. Lower display
      heights increased head and neck flexion with more spinal asymmetry when working
      with paper. The curved desk, designed to provide forearm support, increased
      scapula elevation/protraction and shoulder flexion/abduction.

PMID- 17188895
TI  - An unbiased iterative group registration template for cortical surface analysis.
AB  - Accurate alignment of explicit surface representations of human cerebral cortices
      is necessary in order to compare local individual differences in cortical
      morphometric measurements (thickness, surface area, gyrification, etc.) in both
      normal and clinical populations. This paper presents a methodology for developing
      unbiased, high resolution iterative registration templates from a group of 222
      subject hemispheres and shows that the resulting template provides better
      alignment of a separate set of test data than single-subject templates. It
      demonstrates that between 30 and 50 subjects are required to generate a stable
      iterative template. It also explores the way in which fold variants in
      registration templates affect the quality of registration. Finally, it shows that
      hemisphere-specific group registration templates systematically better register
      subject hemispheres of the same laterality, underlining the need to develop
      templates free of hemisphere bias for asymmetry analysis.

PMID- 17188896
TI  - Optimum template selection for atlas-based segmentation.
AB  - Atlas-based segmentation of MR brain images typically uses a single atlas (e.g.,
      MNI Colin27) for region identification. Normal individual variations in human
      brain structures present a significant challenge for atlas selection. Previous
      researches mainly focused on how to create a specific template for different
      requirements (e.g., for a certain population). We address atlas selection with a
      different approach: instead of choosing a fixed brain atlas, we use a family of
      brain templates for atlas-based segmentation. For each subject and each region,
      the template selection method automatically chooses the 'best' template with the
      highest local registration accuracy, based on normalized mutual information. The
      region classification performances of the template selection method and the
      single template method were quantified by the overlap ratios (ORs) and intraclass
      correlation coefficients (ICCs) between the manual tracings and the respective
      automated labeled results. Two groups of brain images and multiple regions of
      interest (ROIs), including the right anterior cingulate cortex (ACC) and several
      subcortical structures, were tested for both methods. We found that the template
      selection method produced significantly higher ORs than did the single template
      method across all of the 13 analyzed ROIs (two-tailed paired t-test, right ACC at
      t(8)=4.353, p=0.0024; right amygdala, matched paired t test t(8)>3.175, p<0.013;
      for the remaining ROIs, t(8)=4.36, p<0.002). The template selection method also
      provided more reliable volume estimates than the single template method with
      increased ICCs. Moreover, the improved accuracy of atlas-based segmentation using
      optimum templates approaches the accuracy of manual tracing, and thus is valid
      for automated brain imaging analyses.

PMID- 17188897
TI  - Striatal dopamine (D2) receptor availability predicts socially desirable
      responding.
AB  - Research in non-human primates has implicated striatal dopamine (D2) receptor
      function in the expression of social dominance--a fundamental component of social
      extraversion. We predicted that trait extraversion - indexed by the revised
      Eysenck Personality Questionnaire (EPQ-R) - would correlate with striatal DA (D2)
      receptor measures - indexed by [(11)C]-Raclopride binding potential (BP) - in 28
      healthy post-menopausal females (mean age=75 years; range=58-91 years). Region of
      interest (ROI) and voxel-based statistical parametric mapping (SPM) analyses were
      performed, using a reference tissue model for [(11)C]-Raclopride. ROI analysis
      showed moderately significant negative correlations between extraversion and BP
      measures in the left caudate and between psychoticism scores and BP in the right
      putamen. Unexpectedly, scores on the Lie scale, a measure of socially desirable
      responding, were significantly and negatively correlated with BP measures in the
      putamen and survived Bonferroni correction on the right side. After controlling
      for the potential confounding of self-report bias in high Lie scorers, only the
      correlation between Lie scores and BP measures in the right putamen remained
      significant. Voxel-based analysis showed only Lie scores to be significantly and
      negatively correlated with BP measures in the right putamen. We explored this
      association further by applying an ROI-based approach to data on a previously
      scanned sample of young adults (n=13) and found a similar pattern of association,
      which achieved trend level significance in the right putamen. Although
      unanticipated, the relationship observed between BP measures in the right putamen
      and Lie scores is consistent with dopaminergic involvement in socially rewarding
      behaviour. How this relates to dopaminergic tone will need to be further
      explored.

PMID- 17188899
TI  - Effects of the emotional connotations in words on the frontal areas--a spatially
      filtered MEG study.
AB  - The objective of this study was to elucidate how and where emotional connotations
      in words influenced linguistic processing in the language-related areas. We
      recorded neuromagnetic signals in nine right-handed and one left-handed healthy
      volunteers while they silently read emotional and emotionless words written in
      Japanese kanji characters, and investigated the distribution of the cerebral
      oscillatory changes using synthetic aperture magnetometry. Event-related
      desynchronizations (ERDs) in the beta-low gamma bands were observed in the
      anterior cingulate cortex (ACC) that were specific to the reading of emotional
      words in seven of nine right-handers. Beta-low gamma band ERDs were also detected
      in the left inferior or middle frontal gyrus (IFG or MFG) in nine right-handers
      regardless of the tasks. The magnitude of the ERDs in the IFG or MFG was
      significantly greater during emotional-word reading than during emotionless-word
      reading in nine right-handers. Left-dominant ERDs in the beta and gamma bands
      were observed in the prefrontal cortex (PFC) when negative emotional words were
      read (i.e. sadness), while right-dominant ERDs were observed for positive
      emotional words (i.e. happiness) in seven of nine right-handers (p=0.012,
      corrected). In one left-hander, the ERD in the ACC and the greater ERD that
      occurred in the IFG that was specific to emotional-word reading were also
      observed, but their lateralities in the IFG and PFC were reversed. These results
      suggest that emotional connotations in words facilitated the ERDs in the frontal
      language-related areas, and that these facilitations might be modulated by
      emotional processing in the ACC. Furthermore, negative and positive emotional
      words may be processed by different mechanisms.

PMID- 17188898
TI  - Enhanced detection of artifacts in EEG data using higher-order statistics and
      independent component analysis.
AB  - Detecting artifacts produced in EEG data by muscle activity, eye blinks and
      electrical noise is a common and important problem in EEG research. It is now
      widely accepted that independent component analysis (ICA) may be a useful tool
      for isolating artifacts and/or cortical processes from electroencephalographic
      (EEG) data. We present results of simulations demonstrating that ICA
      decomposition, here tested using three popular ICA algorithms, Infomax, SOBI, and
      FastICA, can allow more sensitive automated detection of small non-brain
      artifacts than applying the same detection methods directly to the scalp channel
      data. We tested the upper bound performance of five methods for detecting various
      types of artifacts by separately optimizing and then applying them to artifact
      free EEG data into which we had added simulated artifacts of several types,
      ranging in size from thirty times smaller (-50 dB) to the size of the EEG data
      themselves (0 dB). Of the methods tested, those involving spectral thresholding
      were most sensitive. Except for muscle artifact detection where we found no gain
      of using ICA, all methods proved more sensitive when applied to the ICA
      decomposed data than applied to the raw scalp data: the mean performance for ICA
      was higher and situated at about two standard deviations away from the
      performance distribution obtained on raw data. We note that ICA decomposition
      also allows simple subtraction of artifacts accounted for by single independent
      components, and/or separate and direct examination of the decomposed non-artifact
      processes themselves.

PMID- 17188900
TI  - Scanning for the scanner: FMRI of audition by read-out omissions from echo-planar
      imaging.
AB  - Echo-planar imaging (EPI) generates considerable acoustic noise by rapidly
      oscillating gradients. In functional magnetic resonance imaging (FMRI),
      unshielded EPI sounds activate the auditory system inasmuch as it is responsive.
      Instead of attenuating EPI noise, our goal was to utilize it for auditory FMRI by
      omitting read-outs from the pulse sequence's gradient train. Read-out gradient
      pulses are the primary noise determinant of EPI introducing its peak sound level
      and fundamental frequency peak which inversely relates to twice the echo spacing.
      Using model-driven analyses, we demonstrate that withholding read-outs from EPI
      is suited to reliably evoke hemodynamic blood oxygenation level-dependent (BOLD)
      signal modulations bilaterally in the auditory cortex of normal hearing subjects
      (n=60). To investigate the utility of EPI read-out omissions for auditory FMRI at
      an individual subject's level, we compare traditional Family-Wise-Error-Rate
      (FWER)-corrected maximum height thresholding to spatial mixture modeling (SMM).
      With the latter, appropriate bilateral auditory activations were confirmed in 95%
      of the individuals, whereas FWER-based voxel thresholding detected such
      activations in up to 72%. We illustrate the applicability of this novel EPI
      modification for clinical diagnostic purposes and report on a patient with
      bilateral large vestibular aqueducts (LVAs) and severe binaural sensorineural
      hearing loss (SNHL). In this particular case, read-out omissions from EPI were
      used to assert residual audition prior to cochlear implantation (CI). Requiring
      no specific task compliance or sophisticated stimulation equipment other than the
      scanner on its own, FMRI by read-out omissions lends itself to auditory
      investigations and to quickly probe audition.

PMID- 17188901
TI  - Modeling dendrite density from magnetic resonance diffusion measurements.
AB  - Diffusion-weighted imaging (DWI) provides a noninvasive tool to probe tissue
      microstructure. We propose a simplified model of neural cytoarchitecture intended
      to capture the essential features important for water diffusion as measured by
      NMR. Two components contribute to the NMR signal in this model: (i) the dendrites
      and axons, which are modeled as long cylinders with two diffusion coefficients,
      parallel (D(L)) and perpendicular (D(T)) to the cylindrical axis, and (ii) an
      isotropic monoexponential diffusion component describing water diffusion within
      and across all other structures, i.e., in extracellular space and glia cells. The
      model parameters are estimated from 153 diffusion-weighted images acquired from a
      formalin-fixed baboon brain. A close correspondence between the data and the
      signal model is found, with the model parameters consistent with literature
      values. The model provides an estimate of dendrite density from noninvasive MR
      diffusion measurements, a parameter likely to be of value for understanding
      normal as well as abnormal brain development and function.

PMID- 17188902
TI  - Pattern classification using principal components of cortical thickness and its
      discriminative pattern in schizophrenia.
AB  - We proposed pattern classification based on principal components of cortical
      thickness between schizophrenic patients and healthy controls, which was trained
      using a leave-one-out cross-validation. The cortical thickness was measured by
      calculating the Euclidean distance between linked vertices on the inner and outer
      cortical surfaces. Principal component analysis was applied to each lobe for
      practical computational issues and stability of principal components. And,
      discriminative patterns derived at every vertex in the original feature space
      with respect to support vector machine were analyzed with definitive findings of
      brain abnormalities in schizophrenia for establishing practical confidence. It
      was simulated with 50 randomly selected validation set for the generalization and
      the average accuracy of classification was reported. This study showed that some
      principal components might be more useful than others for classification, but not
      necessarily matching the ordering of the variance amounts they explained. In
      particular, 40-70 principal components rearranged by a simple two-sample t-test
      which ranked the effectiveness of features were used for the best mean accuracy
      of simulated classification (frontal: (left(%)|right(%))=91.07|88.80, parietal:
      91.40|91.53, temporal: 93.60|91.47, occipital: 88.80|91.60). And, discriminative
      power appeared more spatially diffused bilaterally in the several regions,
      especially precentral, postcentral, superior frontal and temporal, cingulate and
      parahippocampal gyri. Since our results of discriminative patterns derived from
      classifier were consistent with a previous morphological analysis of
      schizophrenia, it can be said that the cortical thickness is a reliable feature
      for pattern classification and the potential benefits of such diagnostic tools
      are enhanced by our finding.

PMID- 17188903
TI  - In vivo mapping of functional connectivity in neurotransmitter systems using
      pharmacological MRI.
AB  - Pharmacological MRI (phMRI) methods map the hemodynamic response to drug
      challenge as a surrogate for changes in neuronal activity. However, the central
      effects of drugs can be complex and include activity at the primary site of
      action, downstream effects in other brain regions and direct effects on
      vasculature and neurovascular coupling. Univariate analysis, normally applied to
      phMRI data, does not discriminate between these effects, and can result in
      anatomically non-specific activation patterns. We analysed inter-subject
      correlations in the amplitude of the slow phMRI response to map functionally
      connected brain regions recruited in response to pharmacological challenge.
      Application of D-amphetamine and fluoxetine revealed well-defined functional
      structure underlying the widespread signal changes detected via standard methods.
      Correlated responses were found to delineate key neurotransmitter pathways
      selectively targeted by these drugs, corroborating a tight correspondence between
      the phMRI response and changes in neurotransmitter systems specific to the
      pharmacological action. In vivo mapping of correlated responses in this way
      greatly extends the range of information available from phMRI studies and
      provides a new window into the function of neurotransmitter systems in the active
      state. This approach may provide new important insights regarding the central
      systems underlying pharmacological action.

PMID- 17188904
TI  - Developmental differences in the neural bases of the face inversion effect show
      progressive tuning of face-selective regions to the upright orientation.
AB  - Face inversion hinders face processing in adults, while not affecting children in
      the same way. This fMRI study examines the neural underpinnings of the behavioral
      face inversion effect (FIE) from childhood to adulthood, and how face-selective
      regions in the brain may change with development. Adults, children, and teens
      performed a facial expression decision on upright and inverted face stimuli. In
      the right hemisphere (RH) all age groups showed similar profiles of neural
      activation for upright faces, but important developmental differences occured for
      inverted faces. For inverted faces, adults, and to a lesser degree teens,
      exhibited decreased levels of activity in the face-selective, right lateral
      fusiform gyrus (LFG). However, children exhibited greater activation for inverted
      than for upright faces in the same region. We found similar, but less robust,
      developmental trends in the right superior temporal sulcus (STS) and medial
      fusiform gyrus (MFG). Furthermore, the present study identifies the right LFG as
      the primary neural correlate of the behavioral FIE, and therefore of face
      processing expertise, by showing a significant correlation between the behavioral
      FIE and the neural FIE only in this region. Finally, the present findings shed
      some light on at least one of the possible mechanisms underlying the development
      of face processing expertise, by suggesting a progressive tuning of face
      selective regions in the right hemisphere to the upright orientation, that
      extends well into adolescence.

PMID- 17188905
TI  - Outcome of total claviculectomy in six cases.
AB  - Total claviculectomy is a rare surgical procedure that has been performed for
      more than 90 years for a variety of indications, such as malignancy, trauma, and
      infection. What are the results for the pain score, and what is the influence of
      a total claviculectomy on the range of motion of the shoulder? We could not find
      the answers in the literature and analyzed 6 cases of total claviculectomy. The
      pain scores are good in a chronic osteitis case and in the two malignancy cases.
      In the 3 posttraumatic cases, the indication was pain, and all 3 had poor results
      because of persistent pain. All 6 patients had full range of motion. A resection
      of the entire clavicle did not disturb the motion of the shoulder. A tendency but
      no final conclusions can be drawn because of too few patients and heterogeneous
      indications.

PMID- 17188907
TI  - Calcific tendinitis: natural history and association with endocrine disorders.
AB  - A retrospective, observational cohort study of 102 consecutive patients (125
      shoulders) with calcific tendinitis is presented. Of the patients, 73 (71.6%)
      were women and 29 (28.4%) were men. Compared with population prevalences,
      significant levels of endocrine disorders were found. We compared 66 patients (62
      women [93.9%] and 4 men [6.1%]; mean age, 50.3 years) (81 shoulders) with
      associated endocrine disease with 36 patients (11 women [30.6%] and 25 men
      [69.4%]); mean age, 52.4 years) (44 shoulders) without endocrine disease. The
      endocrine cohort was significantly younger than the non-endocrine cohort when
      symptoms started (mean, 40.9 years and 46.9 years, respectively), had
      significantly longer natural histories (mean, 79.7 months compared with 47.1
      months), and had a significantly higher proportion who underwent operative
      treatment (46.9% compared with 22.7%). Disorders of thyroid and estrogen
      metabolism may contribute to calcific tendinitis etiology. Classifying calcific
      tendinitis into type I (idiopathic) and type II (secondary or endocrine-related)
      aids prognosis and management.

PMID- 17188908
TI  - Arthroscopic treatment for malunion of a head-splitting proximal humeral
      fracture: the need for adequate initial radiologic investigation.

PMID- 17188906
TI  - Reliability, validity, and responsiveness of the simple shoulder test:
      psychometric properties by age and injury type.
AB  - The purpose of this study was to measure the reliability, validity, and
      responsiveness of the Simple Shoulder Test (SST) scale and to examine these in
      patients stratified by age and injury type. Test-retest reliability, content
      validity, criterion validity, construct validity, and responsiveness were
      determined for the SST. The study population comprised 1077 patients with
      shoulder instability and rotator cuff injuries, ranging in age from 14 to 85
      years. The SST demonstrated acceptable test-retest reliability (intraclass
      correlation coefficient >0.90) and content validity (floor and ceiling effects
      <10%). Correlations with the physical functioning component of the Short Form 12
      were significant (r = 0.439, P < .05); however, the correlations were not
      significant when stratified by age group (>60 years) (r = 0.271, P = .349) and
      injury type (rotator cuff injury) (r = 0.337, P = .085). Correlations with the
      American Shoulder and Elbow Surgeons were also significant (r = 0.807, P < .001).
      The construct validity of the SST was acceptable, with all 8 hypotheses
      demonstrating significance (P < .05). The SST was responsive to change (effect
      size, 0.81; standardized response mean, 0.81). However, there were differences
      after stratification for age group and injury type. The SST demonstrated overall
      acceptable psychometric performance; however, differences were found when data
      were stratified by age and injury type.

PMID- 17188909
TI  - Transolecranon anterior fracture dislocation.
AB  - Between January 1996 and July 2003, 93 consecutive patients operated on with a
      diagnosis of olecranon fractures were identified from our trauma unit files.
      Fourteen transolecranon fracture-dislocations were found after a retrospective X
      radiographic evaluation. Eight patients were women and six were men, with a mean
      age of 54 years. There were 4 noncomminuted olecranon fractures, treated with K
      wires and single tension-band wiring. The remaining 10 fractures were complex
      fractures, treated in 3 cases with multiple K-wires and single tension-band
      wiring, in 2 by use of one-third tubular plates, in 1 with a 3.5-mm dynamic
      compression plate, and in the remaining 4 with 3.5-mm reconstruction plates.
      Ligament repair was not performed in any case. Three patients needed reoperation
      because of early failure of primary fixation. Patients were reviewed at a mean
      follow-up of 3.6 years. Two reported difficulties in daily activities, none with
      any symptoms of elbow instability. According to the Broberg and Morrey score, 4
      patients had excellent results, 6 had good results, 2 had fair results, and 2 had
      poor results. Four patients showed signs of degenerative arthritis on the
      radiographs obtained at follow-up. We conclude that transolecranon fracture
      dislocation is an underreported and misdiagnosed injury. Various fixation
      techniques can restore the anatomic relationships and contour of the trochlear
      notch; the imperative goal is to obtain a good stable primary fixation and allow
      early active mobilization.

PMID- 17188910
TI  - Radiographic changes at the elbow in primary osteoarthritis: a comparison with
      normal aging of the elbow joint.
AB  - A retrospective case-control study was undertaken to evaluate the pathologic
      radiographic changes that occur in primary osteoarthritis of the elbow. The
      radiographs of 50 patients with primary osteoarthritis of the elbow were compared
      with an age- and sex-matched control group to distinguish those features specific
      to elbow osteoarthritis from those occurring as a result of normal aging. We
      assessed 100 radiographs (50 anteroposterior and 50 lateral views) in both the
      study and control groups for 10 radiographic features. In the osteoarthritic
      group, osteophytes of the olecranon (96%), coronoid process (90%), radial head
      (86%), and coronoid and radial fossae (64%) were the most frequent findings.
      Joint space narrowing occurred predominantly at the radiocapitellar joint (58%)
      and was more common than at the ulnotrochlear joint (16%). Thickening of the
      olecranon fossa membrane was noted in 68%. In the age- and sex-matched control
      group, coronoid osteophytes occurred in 36% of cases, but the other features were
      rarely observed.

PMID- 17188912
TI  - Fetal alcohol syndrome: case report and review of the literature.
AB  - Due to the significant increase in the incidence and prevalence of the fetal
      alcohol syndrome (FAS) in developing and developed nations, it is important that
      dental professionals recognize this condition. Patients with FAS have orofacial
      characteristics and various psychological and physical symptoms that may affect a
      dental treatment plan. This article reviews the prevalence, incidence, alcohol
      dose response and metabolism, and clinical characteristics of FAS. A case
      demonstrating moderate signs of the condition is included to illustrate some of
      the characteristics.

PMID- 17188911
TI  - Massive rotator cuff tears repaired on top of humeral head by McLaughlin's
      procedure.
AB  - The clinical and radiographic outcomes of McLaughlin's procedure for massive
      rotator cuff tears were investigated in 25 shoulders, in which the cuff tears
      were so severe that the tendons were sutured on the top of the humeral head. The
      mean age at surgery was 62.2 years (range, 39-74 years). The mean follow-up
      period was 50 months (range, 24-80 months). The University of California, Los
      Angeles score significantly improved from 10.9 to 31.8 points postoperatively;
      the postoperative result was classified as excellent in 11 shoulders, good in 11,
      and poor in 3. Osteoarthritis progressed postoperatively in 7 shoulders (28%),
      and upper migration of the humeral head progressed in 6 (24%), although both
      progression rates were no higher than those for other common procedures. When
      torn tendons reach over the top of the humeral head with the arm at the side in
      patients with massive tears that are not reparable to the greater tuberosity,
      satisfactory clinical outcomes can be expected.

PMID- 17188913
TI  - Hemangiomas of the head and neck with phleboliths: clinical features, diagnostic
      imaging, and treatment of 3 cases.
AB  - Hemangiomas are benign vascular lesions and are classified into cavernous,
      capillary, and mixed types. Phleboliths are calcified nodules that can be
      regarded as a pathognomic feature of hemangioma. The treatment of the hemangiomas
      is based on location, accessibility, depth of invasion, age, and cosmetic
      considerations. Surgical extirpation is a mainstay of treatment when indicated.
      Three cases of head and neck hemangioma are reported with clinical and imaging
      findings.

PMID- 17188914
TI  - Protein 4.2 Komatsu (D175Y) associated with the lack of interaction with ankyrin
      in human red blood cells.
AB  - Membrane skeletal proteins play an important role in regulating the shape and
      function of the human red blood cell. Protein 4.2 interacts with cytoplasmic
      domain of band 3 (CDB3) and ankyrin for association between the skeleton network
      and the membrane. The deficiency of protein 4.2 may result in hereditary
      spherocytosis. In order to explore the molecular mechanism of the linkage of
      protein 4.2 Komatsu (D175Y) and protein 4.2 Nippon (A142T) with hereditary
      spherocytosis, a series of protein 4.2-derived mutants were designed and
      expressed in Escherichia coli. Their interactions with ankyrin and CDB3 were
      investigated by Far Western blot and pull-down assay in vitro. The results showed
      that the mutant D175Y of protein 4.2 cannot interact with ankyrin while mutant
      A142T, just like normal protein 4.2, can bind to ankyrin directly and can
      associate with CDB3 in the presence of ankyrin. Based on comparing the binding
      abilities of the protein 4.2 mutants D175F, D175A, D175K and D175Y with ankyrin
      and CDB3, we suggested that defective binding of protein 4.2 Komatsu to ankyrin
      is resulted from the charge effect of amino acid residue 175 substitution (D-
      >Y), which leads to significant structural change in protein 4.2 function domain.

PMID- 17188915
TI  - Red blood cell senescence and neocytolysis in humans after high altitude
      acclimatization.
AB  - A selective lysis of relatively young erythrocytes (neocytolysis), together with
      a decrease of erythropoietin (EPO) production, has been described in
      polycythemic, high altitude acclimatized climbers, after descent to sea level,
      and in astronauts, soon after exposure to weightlessness (Alfrey CP, Rice L,
      Udden MM, Driscoll TB. Neocytolysis may represent the physiological down
      regulation of red-cell mass. Lancet 349 (1997) 1389-90). To study neocytolysis,
      we analysed blood samples drawn from 4 mountain climbers at sea level before and
      after 53 days of high altitude acclimatization (> or = 4500 m). After a 6-day
      descent to sea level, erythropoietin (EPO) plasma levels were lower than before
      high altitude acclimatization (mean values: 2.5+/-3.3 versus 10+/-4.5 mIU/ml, p <
      0.05). Red blood cell (RBC) populations were separated into low, middle and high
      density subsets, which, by physical and phenotypical criteria, were characterized
      as young, middle-aged and old. RBC membrane molecules CD55 and CD59 along with
      phosphatydylserine and CD47 were measured. The former are partially lost during
      RBC aging. The latter are involved in the triggering or inhibition of RBC
      phagocytosis by macrophages. Immunofluorescence and flow cytometry were done on
      each density subset. Young and middle-aged RBCs largely disappeared after descent
      from high altitude (from 4.50% (+/-3.10) and 66% (+/-6.90) to 0.19% (+/-0.07) and
      1.90% (+/-0.50), respectively). Simultaneously, there was a dramatic increase of
      high density RBCs (from 29.50% (+/-7) to 97.90% (+/-2.00)). Furthermore, the
      remaining young and middle-aged RBCs had acquired a senescent-like phenotype,
      which may account for their increased susceptibility to phagocytosis.

PMID- 17188917
TI  - Continuous EEG monitoring in a paediatric intensive care unit.
AB  - Monitoring with continuous EEG (cEEG) has become a valuable tool in the adult
      neurointensive care unit. The benefits of cEEG or amplitude-integrated EEG in
      neonatal intensive care have also been described. The aim of the present study
      was to describe and evaluate the use of cEEG in a paediatric intensive care unit.
      The study is a description of children and adolescents with acute neurological
      disorders monitored by cEEG in a paediatric intensive care unit for more than
      12h. The indication for cEEG and the outcome are reported for 54 patients during
      a 4-year period. Twelve patients were monitored for high intracranial pressure,
      eight of whom died. Fourteen were monitored due to suspected, but not detected,
      epilepsy, their underlying diagnoses being variable. Refractory status
      epilepticus was the reason for cEEG in 24 cases. All of these patients survived
      the acute phase of status epilepticus. Four patients had seizure activity on cEEG
      due to global anoxia; these were not classified as status epilepticus. In
      conclusion, in the paediatric intensive care unit the most important indication
      for cEEG monitoring is in patients with suspected refractory status epilepticus
      where it adds to the diagnosis and choice of treatment. Continuous EEG should
      therefore be part of the paediatric intensive care unit technical support to
      select and monitor, among children with critical neurological disorders, those
      with refractory status epilepticus.

PMID- 17188916
TI  - Glutaric aciduria type 1: clinical, biochemical and molecular findings in
      patients from Israel.
AB  - Glutaric aciduria type 1 (GA1) is a rare cerebral organic aciduria which
      typically manifests as an acute encephalopathic crisis followed by profound long
      term neurological handicap. We report the diagnosis of 12 new patients from a
      single laboratory in Israel during a 5-year period. Eleven of the 12 were of
      Palestinian origin, and only two were related. One patient was asymptomatic
      whilst one was mildly, one moderately and nine severely affected, two of whom had
      unusual MRI findings. Two patients had normal glutaric acid excretion and normal
      blood glutarylcarnitine levels yet glutarylcarnitine excretion was increased,
      indicating its utility as a diagnostic marker. Four novel GCDH mutations
      (Thr193_Arg194insHis, Asn329Ser, Thr341Pro, Met405Val) and five previously
      reported mutations (Ser119Leu, Leu283Pro, Ala293Thr, Gly390Arg and Thr416Ile)
      were identified. Severely and mildly affected or even asymptomatic patients
      shared the same genotypes (Thr416Ile/Thre416Ile and
      Aal293Thr/Thr193_Arg194insHis). Knowledge of the responsible mutation enabled
      successful prenatal diagnosis on chorionic villous DNA in three families. In
      conclusion, GA1 is genetically heterogeneous and has a relatively high incidence
      in the Palestinian population, reflecting the historical tradition of marriages
      within extended kindreds, particularly in isolated villages. Additional genetic
      and/or environmental factors must account for the phenotypic heterogeneity in
      patients with the same genotype. The diagnosis was not suspected in the majority
      of cases despite typical clinical and/or neuroimaging features, suggesting that
      glutaric aciduria may be under-diagnosed. Greater awareness of glutaric aciduria
      amongst pediatricians, neonatologists and radiologists is the key to identifying
      the disorder in the presymptomatic phase and preventing its catastrophic
      consequences.

PMID- 17188918
TI  - Magnetic field homogeneity: a new approach to orthogonalizing and optimizing shim
      gradients.
AB  - A new approach to optimizing shim coil currents for magnetic resonance magnets is
      presented. The new approach orthogonalizes the shim coil gradients to allow a
      simple one-dimensional optimization for each orthogonalized "composite shim." The
      technique demands no specialized equipment, requiring only the acquisition of
      simple one-dimensional NMR spectra. Examples from two high-resolution NMR
      spectrometers are presented, where the shim currents found by the new algorithm
      provide higher resolution than was obtained by the spectrometer vendor's
      installation engineers using field-mapping techniques. The examples shown
      demonstrate the advantages of the technique for high-resolution NMR, but we
      expect the approach will also find application in a broad variety of areas
      including imaging and in vivo spectroscopy.

PMID- 17188919
TI  - Symmetry-based recoupling of proton chemical shift anisotropies in ultrahigh
      field solid-state NMR.
AB  - A two-dimensional NMR experiment for estimating proton chemical shift
      anisotropies (CSAs) in solid powders under magic-angle spinning conditions is
      demonstrated in which 1H CSAs are reintroduced with a symmetry-based recoupling
      sequence while the individual proton sites are resolved according to their
      isotropic chemical shifts by magic-angle spinning (MAS) or combined rotation and
      multiple pulse (CRAMPS) homonuclear decoupling. The experiments where carried out
      on an ultrahigh-field solid-state NMR instrument (900 MHz 1H frequency) which
      leads to increased resolution and reliability of the measured 1H CSAs. The
      experiment is expected to be important for investigating hydrogen bonding in
      solids.

PMID- 17188920
TI  - Molecular mass estimation by PFG NMR spectroscopy.
AB  - A simplified PFG NMR diffusion analysis method was developed to estimate the
      molecular mass of small molecules in dilute aqueous and organic solutions.
      Internal referencing was utilized to improve the experimental robustness and
      simplify the data analysis. Specifically, tetramethylsilane (TMS) and HDO were
      chosen for the organic and aqueous reference molecules, respectively. Relative
      diffusivity-molecular mass correlations were empirically developed in the range
      of 2-1280 g/mol for dilute CDCl3 and D2O solutions. The median error in the
      predicted molecular mass was found to be 10 rel%. The utility of the method was
      demonstrated by analyzing the major and minor components in olive oil.

PMID- 17188921
TI  - Differential expression of eight transcripts and their roles in the cuticle of
      the blue crab, Callinectes sapidus.
AB  - Eight cuticle protein transcripts from Callinectes sapidus were sequenced and
      their expression determined across the molt cycle in both calcifying and
      arthrodial cuticle hypodermis using quantitative PCR, Northern blots, and in situ
      hybridization. Four transcripts, designated CsAMP, are found only in non
      calcifying arthrodial membrane hypodermis. They all code for a Rebers-Riddiford-1
      motif, known to bind chitin. CsAMP9.3 is most likely an exocuticle constituent
      since it is expressed only during pre-molt. The other three arthrodial
      transcripts are present both before and after ecdysis. One of these, CsAMP16.3,
      codes for a RGD cell-attachment motif that could be involved in anchoring chitin
      protein fibers to pore canals, cellular extensions of the hypodermis in the
      cuticle. The other four transcripts, designated CsCP, were found only in
      calcifying hypodermis. CsCP14.1 contains an RR-1 motif, which is more commonly
      found in non-calcifying cuticle proteins. CsCP6.1 is expressed post-molt and
      contains a partial RR motif, suggesting that it could bind to chitin in the
      endocuticle. The other two transcripts from calcifying hypodermis do not code for
      RR proteins, but both contain three copies of a different insect cuticle motif.
      One of these, CsCP19.0, is expressed only post-molt while the other, CsCP15.0, is
      present both before and after ecdysis.

PMID- 17188922
TI  - Prevalence and treatment of non-motor symptoms in Parkinson's disease.

PMID- 17188923
TI  - Anterior positional fault of the fibula after sub-acute lateral ankle sprains.
AB  - Recent evidence has suggested a positional fault of the fibula exists in
      chronically unstable ankles. However, there has been little research examining
      positional faults after a sub-acute lateral ankle sprain (LAS). Our purpose was
      to measure the position of the distal fibula in relation to the distal tibia in
      subjects with sub-acute LASs and to determine if there is a relationship between
      the amount of swelling and fibular position. Eleven subjects with a unilateral
      sub-acute LAS and 11 healthy controls participated. The Wilcoxon signed rank test
      revealed a significant (p=0.008) difference within the ankles of the injured
      group. The sprained ankles had a mean fibular position of 14.2+3.4 mm and were
      positioned significantly more anteriorly than the contralateral uninjured ankles
      (17.0+3.2 mm). The Mann-Whitney test revealed a significant difference (p=0.045)
      between the sprained ankle and the side-matched limbs of the controls (16.8+2.3)
      Pearson product moment correlations revealed a strong positive correlation
      between fibular position and swelling (r=0.793, p=0.004). Those ankles with more
      swelling had the most anteriorly positioned fibulae. The fibulae in sub-acutely
      sprained ankles appear to be positioned more anteriorly compared to the
      contralateral ankles. This positional fault may be maintained acutely by
      swelling.

PMID- 17188924
TI  - The active straight leg raising test (ASLR) in pregnant women: differences in
      muscle activity and force between patients and healthy subjects.
AB  - Pregnancy-related low back and pelvic pain (PLBP) is a frequent complication of
      pregnancy. Although pathological mechanisms underlying PLBP are obscure,
      dysfunction of the sacroiliac joints (SI-joints) seems to play an important role.
      A cross-sectional study was performed on 24 pregnant women with and without PLBP.
      The objective was to determine muscle activation patterns of trunk and leg
      muscles during the active straight leg raising test (ASLR) and static hip
      flexion, and to determine maximal hip flexion force at 0 and 20 cm leg raise
      height. Moreover, the effort to raise the leg was scored. The measurements
      resulted in several significant differences between the patients and healthy
      controls; among others (a) patients scored subjectively more effort during ASLR,
      (b) at both 0 and 20 cm leg raise height patients had less hip flexion force, and
      (c) patients developed more muscle activity during ASLR. Since pregnant women
      with PLBP developed a higher muscle activity during ASLR with a significantly
      lower output at 0 and 20 cm than healthy pregnant women, it could be proposed
      that the ASLR demonstrates a disturbed load transfer across the SI-joints in this
      population.

PMID- 17188925
TI  - Pregnane X receptor: promiscuous regulator of detoxification pathways.
AB  - The Pregnane X Receptor (PXR) is pivotal for the body's response to toxic
      xenobiotics and endogenous metabolites. By acting as a ligand-activated
      transcription factor, PXR regulates all stages of xenobiotic metabolism and
      transport and is responsible for important inductive drug interactions. Screening
      assays to assess the PXR activation potential of new and existing drugs are
      becoming integral components of drug discovery programs. PXR is also involved in
      lipid homeostasis providing opportunities for treatments based on PXR agonists
      for diseases involving aberrant cholesterol and bile acid levels. The expression
      of PXR in many other tissues besides liver and intestine suggest PXR may have
      additional protective functions in the body, which contribute to disease outcomes
      in diverse clinical situations with potential for novel therapeutic approaches.

PMID- 17188926
TI  - Characterization of the West Nile virus protease substrate specificity and
      inhibitors.
AB  - West Nile virus (WNV), a mosquito-borne member of Flaviviridae, is a human
      pathogen causing widespread disease for which there is no vaccine or
      chemotherapy. The two-component viral serine protease consists of a heterodimeric
      complex between the hydrophilic domain of the cofactor, NS2B (NS2BH) and the
      protease domain (NS3-pro). The protease is essential for polyprotein processing
      followed by assembly of viral replicase and genome replication. Therefore, the
      protease is an excellent target for development of antiviral therapeutics. Here,
      we report the expression in Escherichia coli, purification, and characterization
      of biochemical and kinetic properties of the WNV protease. Furthermore, we show
      that the WNV and the dengue virus type 2 (DENV-2) proteases are inhibited by
      aprotinin with inhibitor constants of 0.16 and 0.026 microM, respectively.
      Molecular modeling of the WNV protease/aprotinin complex, based on the known
      crystal structures of the WNV NS2BH-N3pro and aprotinin, suggest a potentially
      strong interaction between the P2 Lys and the protease activator peptide, NS2BH.
      This conclusion based on molecular modeling is in agreement with our data of a
      higher k(cat)/Km value with the substrate, Boc-Gly-Lys-Arg-MCA than the Boc-Gly
      Arg-Arg-MCA and is also consistent with the results of an earlier study that were
      based on substrate-based inhibitor peptides.

PMID- 17188927
TI  - Exploring the neural basis of cognition: multi-modal links between human fMRI and
      macaque neurophysiology.
AB  - Although functional magnetic resonance imaging (fMRI) with sophisticated
      behavioral paradigms has enabled the investigation of increasingly higher-level
      cognitive functions in humans, these studies seem to lose touch with
      neurophysiological studies in macaque monkeys. The application of fMRI and other
      MRI-based techniques to macaque brains allows studies in the two species to be
      linked. fMRI in human and macaque subjects using equivalent cognitive tasks
      enables direct comparisons of the functional brain architecture, even for high
      level cognitive functions. Combinations of functional or structural MRI and
      microelectrode techniques provide ways to explore functional brain networks at
      multiple spatiotemporal scales. These approaches would illuminate the
      neurophysiological underpinnings of human cognitive functions by integrating
      human functional neuroimaging with macaque single-unit recordings.

PMID- 17188928
TI  - Predictive data mining in clinical medicine: current issues and guidelines.
AB  - BACKGROUND: The widespread availability of new computational methods and tools
      for data analysis and predictive modeling requires medical informatics
      researchers and practitioners to systematically select the most appropriate
      strategy to cope with clinical prediction problems. In particular, the collection
      of methods known as 'data mining' offers methodological and technical solutions
      to deal with the analysis of medical data and construction of prediction models.
      A large variety of these methods requires general and simple guidelines that may
      help practitioners in the appropriate selection of data mining tools,
      construction and validation of predictive models, along with the dissemination of
      predictive models within clinical environments. PURPOSE: The goal of this review
      is to discuss the extent and role of the research area of predictive data mining
      and to propose a framework to cope with the problems of constructing, assessing
      and exploiting data mining models in clinical medicine. METHODS: We review the
      recent relevant work published in the area of predictive data mining in clinical
      medicine, highlighting critical issues and summarizing the approaches in a set of
      learned lessons. RESULTS: The paper provides a comprehensive review of the state
      of the art of predictive data mining in clinical medicine and gives guidelines to
      carry out data mining studies in this field. CONCLUSIONS: Predictive data mining
      is becoming an essential instrument for researchers and clinical practitioners in
      medicine. Understanding the main issues underlying these methods and the
      application of agreed and standardized procedures is mandatory for their
      deployment and the dissemination of results. Thanks to the integration of
      molecular and clinical data taking place within genomic medicine, the area has
      recently not only gained a fresh impulse but also a new set of complex problems
      it needs to address.

PMID- 17188929
TI  - Single-trial evoked potential estimation: comparison between independent
      component analysis and wavelet denoising.
AB  - OBJECTIVE: Brain responses to repeated sensory stimuli are typically buried in
      the more prominent background activity, and thus analysis of these responses on a
      single-trial basis would require advanced procedures to estimate the brain
      activity related only to the experimental task. Recently, we have proposed a new
      iterative independent component analysis (iICA) approach to estimate single-trial
      responses. In this paper, we compare the performance of iICA at estimating single
      trial responses with ensemble averaging and wavelet transform (WT) denoising.
      METHODS: We analyzed simulated evoked potentials (EPs) and actual recordings of
      the auditory N100 component from 33 normal subjects, and the performance of each
      method was quantified in terms of the average root-mean-square error and average
      correlation before and after processing. RESULTS: We found that WT gave a
      smoother overall average EP, while iICA could isolate the N100 component out of
      the entire EP waveform. With simulated data, iICA provided significantly better
      estimates of the true EP compared to plain averaging (p<0.01) and WT (p<0.01).
      With actual data, iICA showed clear responses in single trials, in all subjects.
      Additionally, the corresponding average EPs had a sharper N100-P200 complex, with
      flatter preceding and following regions, resulting in an enhanced N100 component.
      CONCLUSIONS: The iICA procedure can provide clear responses in each single trial,
      and the resulting average N100 component is significantly improved compared to
      plain averaging and wavelet denoising. SIGNIFICANCE: The proposed technique may
      have a significant impact as a clinical tool in the analysis of single-trial
      responses.

PMID- 17188930
TI  - Reasons for seeking acute care in chronic heart failure.
AB  - BACKGROUND: Patients with chronic heart failure (CHF) have frequent episodes of
      exacerbation leading to recurrent hospitalization. AIMS: To explore factors
      related to patients seeking care for worsening CHF. METHODS: Eighty-eight
      patients diagnosed with a deteriorating CHF condition were interviewed. Data were
      analysed using content analysis. RESULTS: Overall, 51 (58%) patients sought
      emergency care because of their symptoms while 37 (42%) were either sent by
      relatives or referred from outpatient clinics. Delay in seeking care was
      explained by 62 (71%) patients as a "wait and see" strategy, 9 (10%) were
      reluctant to use the health care system and 10 (11%) felt that it was futile to
      seek care. Fifty percent of the patients were uncertain about their current
      deteriorating status. Only 4 patients reported their symptoms to be related to
      heart failure. CONCLUSIONS: Although symptoms were the dominant reason for
      seeking emergency care, only a few patients related their symptoms to worsening
      CHF, which might be an important factor for not seeking emergency care earlier.
      Patient education programs should make efforts to improve understanding of
      symptom recognition.

PMID- 17188931
TI  - Ecology of testate amoebae from mires in the Central Rhodope Mountains, Greece
      and development of a transfer function for palaeohydrological reconstruction.
AB  - Testate amoebae are useful environmental indicators in ecological and
      palaeoecological studies from peatlands. Previous quantitative studies have
      focused on the peatlands of Northern and Central Europe, North America, and New
      Zealand and have considered a relatively restricted variety of peatland types,
      mostly ombrotrophic or Sphagnum-dominated while more minerotrophic fens have been
      less studied. Here we present the first quantitative ecological study of testate
      amoebae from four small mesotrophic fens (pH 5.5-8.1) in the Elatia Forest,
      northern Macedonia province, Greece. Relationships with the environmental data
      were investigated using redundancy analysis and mantel tests. Transfer function
      models were derived using a variety of techniques. Results demonstrate that as
      for Sphagnum-dominated mires hydrology is the most important control on amoebae
      community composition. Transfer function models should enable water tables to be
      predicted within 2.5 cm, when data selection is used this is reduced to less than
      2 cm. pH is also an important environmental control on testate amoebae
      communities, a transfer function model enables pH prediction within 0.4 pH units.
      The hydrological transfer function is the best performing such model yet produced
      in terms of prediction error. This study provides new data on the ecology of
      testate amoebae in fens, and the transfer function models should allow
      quantitative palaeohydrological reconstruction.

PMID- 17188932
TI  - Multidimensional analysis of metabolism contributions involved in running track
      tests.
AB  - It is difficult to interpret the training induced changes in middle-distance
      running, since numerous aerobic and anaerobic determinants of the performance are
      interdependent. Several aerobic and anaerobic tests are available but their
      results, particularly those from anaerobic tests, may be discordant, not
      providing univocal interpretation of training. The purpose of this study is to
      use a multidimensional approach to distinguish aerobic and anaerobic capacities
      assessed by two running tests on a track: the maximal anaerobic running test
      (MART) and V(O2max) tests. Eleven runners carried out two maximal tests on a
      synthetic track before and after a 4-week training period: (i) a maximal test to
      determine V(O2max), the velocity associated with V(O2max) (vV(O2max)) and the
      velocity at the lactate threshold (v(LT)), (ii) a maximal anaerobic running test
      to estimate anaerobic capacity. An all-out test run at v(LT)+50% of the
      difference between v(LT) and vV(O2max), known to be affected by both aerobic and
      anaerobic energy production, was used to test this approach. A principal
      components analysis (PCA) shows that two components (i.e., aerobic and anaerobic)
      explained 79% of the variation in the physiological variables. The PCA suggests
      that V(O2max) and MART tests assess the aerobic and the anaerobic capacities,
      respectively. In contrast, the performance in the all-out test is affected by
      both aerobic and anaerobic energy production. The PCA shows that v(LT) and DeltaP
      (difference between the maximal power of the MART and V(O2max)) are clear markers
      of the long-term endurance and the anaerobic capacity, respectively. This
      multidimensional approach can be a useful way to disentangle the aerobic and
      anaerobic components of track tests.

PMID- 17188933
TI  - Guidelines for the diagnosis and management of familial dilated cardiomyopathy.

PMID- 17188934
TI  - Guidelines for the diagnosis and management of hypertrophic cardiomyopathy.

PMID- 17188935
TI  - Guidelines for the diagnosis and management of Marfan syndrome.

PMID- 17188936
TI  - Guidelines for the diagnosis and management of familial hypercholesterolaemia.

PMID- 17188937
TI  - A nurse-/pharmacy-led capecitabine clinic for colorectal cancer: results of a
      prospective audit and retrospective survey of patient experiences.
AB  - Oral chemotherapy agents provide patients with choice and home-based therapy but
      demand greater emphasis on patient support and education to minimise toxicities.
      To meet this demand, a nurse-/pharmacy-led clinic was established at the Beatson
      Oncology Centre in 2003 for the provision of oral capecitabine to metastatic
      colorectal cancer patients to provide a controlled and supportive environment. We
      conducted a prospective audit of 52 patients attending the clinic from March 2003
      to June 2004 and a retrospective survey of patient experiences to assess clinic
      effectiveness. Of 52 patients, 79% completed at least 3 cycles of treatment (mean
      3.5). Capecitabine was well tolerated. The dose was reduced on at least one
      occasion in 15 (29%) patients and 17 (30%) patients experienced at least one
      delay. Patient satisfaction, indicated by questionnaire responses (n=27), was
      high. Most patients (> or =85%) thought that the service provision was useful and
      well organised. The results indicate that a nurse-/pharmacy-led clinic for the
      provision of home-based oral capecitabine is safe, effective and acceptable to
      most patients. The success of this clinic can provide a model for use in other
      centres and in other types of cancer, such as breast cancer, where oral
      chemotherapy is a treatment option.

PMID- 17188938
TI  - Developing and piloting a nurse-led model of follow-up in the multidisciplinary
      management of colorectal cancer.
AB  - One of the main challenges of colorectal cancer follow-up is the detection of
      early disease in order to influence survival and improve outcome. Yet, the
      benefits of follow-up are not only related to survival. It is well documented
      that patients can experience an array of problems following colorectal cancer
      surgery which impact upon quality of life, therefore symptom management plays an
      important part in the overall spectrum of follow-up care. In addition, there is
      emerging evidence to suggest that clinical nurse specialists are well placed in
      the multidisciplinary team to co-ordinate such follow-up programmes. This paper
      reports on a pilot study designed to assess the feasibility of a follow-up
      programme led by nurse specialists for patients with colorectal cancer. Key
      outcome areas were adherence to an agreed follow-protocol, quality of life,
      patient and clinician satisfaction and a cost-analysis of the new model. The
      study was conducted over one year with 60 patients. This redesign resulted in a
      smoother pathway of follow-up care, improved quality of life and acceptance to
      both patients and clinicians alike. The introduction of a nurse-led follow-up
      model is expected to demonstrate cost savings over a 3 year rolling follow-up
      programme.

PMID- 17188939
TI  - How do participants of a post registration oncology nursing course perceive that
      the course influences their practice?--A descriptive survey.
AB  - The high incidence of cancer necessitates informed and skilled cancer care, a
      concept highlighted in a number of Government reports. However, there is little
      research, which explores the relationship between cancer education and practice.
      This paper reports a descriptive survey to explore the perceived impact of a post
      registration oncology-nursing course on practice. It aimed to determine how much
      the oncology nursing course impacted on practice and what aspects impacted the
      most. Postal questionnaires, using primarily closed questions, were sent to all
      post-registration nurses (n=171) who had undertaken an oncology-nursing course at
      one cancer centre between 1996 and 2003. The course was perceived to have a
      positive impact on practice and the subjects perceived to be most beneficial
      included those relating to communication skills, attitudes to cancer and
      psychological support. In conclusion, the study suggested that there is a
      positive relationship between oncology education and practice. This research may
      be used to inform discussions to support current and future investment in
      oncology education.

PMID- 17188941
TI  - Sample size calculation for multicenter randomized trial: taking the center
      effect into account.
AB  - In multicenter trials, data from the same center are more similar than those from
      different centers. These similarities induce a correlation between data, known as
      the center effect, which is assessed by the intraclass correlation coefficient
      (ICC). Here, we derive a sample size formula for continuous data that takes into
      account this center effect. Our analytical developments lead to an elementary
      formula different from the classical one by a (1-rho) factor, where rho is the
      ICC. This work allows for adjusting and reducing the sample size according to the
      magnitude of the center effect and leads to a better consistency in the conduct
      of multicenter randomized trials.

PMID- 17188940
TI  - Effects of combined administration of captopril and DMSA on arsenite induced
      oxidative stress and blood and tissue arsenic concentration in rats.
AB  - We compared the therapeutic efficacy of captopril and a thiol chelating agent,
      meso 2,3-dimercaptosuccinic acid (DMSA) either individually or in combination
      against arsenite induced oxidative stress and mobilization of metal in rats.
      Animals were exposed to 100 ppm arsenite as sodium arsenite in drinking water for
      six weeks followed by treatment with DMSA (50 mg/kg, orally), captopril (50
      mg/kg, intraperitoneally) either alone or in combination, once daily for 5
      consecutive days. Arsenite exposure led to a significant depletion of blood delta
      aminolevulinic acid dehydratase (ALAD) activity, glutathione and platelet levels
      while significantly increased the level of reactive oxygen species (in RBCs).
      Hepatic reduced glutathione (GSH) level showed a significant decrease while,
      thiobarbituric acid reactive substances (TBARS) levels increased on arsenite
      exposure indicating arsenite induced hepatic oxidative stress. Kidney GSH, GSSG,
      catalase and TBARS remained unchanged on arsenite exposure. Treatment with DMSA
      was effective in increasing ALAD activity while, captopril was ineffective when
      given alone. Captopril when co-administered with DMSA also provided no additional
      beneficial effect on blood ALAD activity but significant brought altered platelet
      counts back to the normal value. In contrast, administration of captopril alone
      provided significant beneficial effects on hepatic oxidative stress, and in
      combination with DMSA provided a more pronounced recovery in the TBARS level
      compared to the individual effect of DMSA and captopril. Renal biochemical
      variables remained insensitive to arsenite and any of the treatments.
      Interestingly, combined administration of captopril with DMSA had a remarkable
      effect in depleting total arsenic concentration from blood and soft tissues.
      These results lead us to conclude that captopril administration during chelation
      treatment had some beneficial effects particularly on the protection of inhibited
      blood ALAD activity, and depletion of arsenic level. The study supports our
      earlier conclusion that a co-administration of an antioxidant is more beneficial
      than monotherapy with the chelating agents, in order to achieve optimal effects
      of chelation in arsenite toxicity.

PMID- 17188942
TI  - Influence of cardiopulmonary reflex on the sympathetic activity during myocardial
      infarction.
AB  - The time-course of changes in renal sympathetic nerve activity (RSNA), arterial
      and cardiopulmonary baroreflexes sensitivities was evaluated in conscious rats
      eight hours (8 h) and ten days (10 day) after myocardial infarction (MI), induced
      by coronary artery ligation. RSNA was recorded by a platinum electrode implanted
      in left renal nerve. Arterial and cardiopulmonary baroreflexes sensitivities were
      evaluated by changes in blood pressure and serotonin administration,
      respectively. Both 8 h and 10 day groups presented hypotension (103+/-4 vs. 102+/
      2 vs. 115+/-4 mm Hg), but only 8 h showed tachycardia (422+/-22 vs. 378+/-11 vs.
      384+/-9 bpm) when compared to Control rats. RSNA was depressed 8 h after MI and
      increased in 10 day group (12+/-2 vs. 39+/-8 vs. 22+/-2 mV/cycle). Although
      arterial baroreflex control of heart rate was similar in all groups, the arterial
      baroreflex control of RSNA in 8 h group was impaired during reductions (-0.35+/
      0.10 vs. -1.66+/-0.23 vs. -0.09+/-0.14 mV/cycle/mm Hg) or increases (-0.77+/-0.17
      vs. -1.63+/-0.58 vs. -1.66+/-0.17 mV/cycle/mm Hg) in blood pressure when compared
      to Control animals. Moreover, cardiopulmonary baroreflex bradycardic response was
      increased in 8 h rats and normalized in 10 day group. The results suggest that
      the increased cardiopulmonary baroreflex sensitivity in 8 h may contribute to the
      reduction in the tonic level of RSNA as well as in the impairment of the
      baroreflex control of RSNA in the presence of hypotension.

PMID- 17188943
TI  - Evaluating genetic differentiation of Anopheles arabiensis in relation to larval
      habitats in Kenya.
AB  - Anopheles arabiensis, an important vector of malaria in sub-Saharan Africa shows
      great versatility in utilizing a broad range of larval habitats. Most studies on
      the population genetic structure of this species have focused on adult mosquitoes
      collected mainly indoors and have found populations within relatively short
      distances to be panmictic. Various authors suggested that the incipient
      speciation between the chromosomal forms of Anopheles gambiae s.s. in West Africa
      involved adaptation to different habitats of larvae. To investigate if similar
      process occurs in An. arabiensis, we analyzed samples from four different larval
      habitats alongside a sample of adult mosquitoes collected indoors at eight
      microsatellite loci. We tested the hypothesis that An. arabiensis is subdivided
      into populations that are adapted to exploit different larval habitats. Overall,
      the level of genetic differentiation among the larval subpopulations was low with
      the mean pairwise Fst estimate based on information from all the loci being
      0.0232 (P=0.1691) although differentiation was only significant for comparisons
      between certain larval samples and the adult samples. In addition, there was
      strong evidence against subdivision among larvae when multilocus simultaneous
      assignment tests were used. These results do not provide sufficient support for
      the hypothesis that An. arabiensis is subdivided into subpopulations that
      specialize to exploit different larval habitats.

PMID- 17188944
TI  - Replication of 2-hydroxyadenine-containing DNA and recognition by human
      MutSalpha.
AB  - 2-Hydroxyadenine (2-OH-A), a product of DNA oxidation, is a potential source of
      mutations. We investigated how representative DNA polymerases from the A, B and Y
      families dealt with 2-OH-A in primer extension experiments. A template 2-OH-A
      reduced the rate of incorporation by DNA polymerase alpha (Pol alpha) and Klenow
      fragment (Kf(exo-)). Two Y family DNA polymerases, human polymerase eta (Pol eta)
      and the archeal Dpo4 polymerase were affected differently. Bypass by Pol eta was
      very inefficient whereas Dpo4 efficiently replicated 2-OH-A. Replication of a
      template 2-OH-A by both enzymes was mutagenic and caused base substitutions. Dpo4
      additionally introduced single base deletions. Thermodynamic analysis showed that
      2-OH-A forms stable base pairs with T, C and G, and to a lesser extent with A.
      Oligonucleotides containing 2-OH-A base pairs, including the preferred 2-OH-A:T,
      were recognized by the human MutSalpha mismatch repair (MMR). MutSalpha also
      recognized 2-OH-A located in a repeat sequence that mimics a frameshift
      intermediate.

PMID- 17188945
TI  - Reproducibility of cardioventilatory measurements using a respiratory mass
      spectrometer.
AB  - The aim of this study was to assess the within subject reproducibility of
      cardioventilatory measurements and the maximum permitted 'normal' variability
      over time at rest and exercise using the respiratory mass spectrometer (RMS). Ten
      subjects underwent an incremental exercise test on three separate occasions
      utilising rebreathing (RB) and helium dilution mixed expired gas analysis (HME)
      functions of the RMS. Measurements included heart rate (HR), oxygen consumption
      (V(O2)), carbon dioxide excretion (V(VO2)), effective pulmonary blood flow
      (Q(eff)), stroke volume (SV), arteriovenous oxygen content difference (AVO),
      transfer factor (Dl(CO)), functional residual capacity (FRC), minute ventilation
      (VE), tidal volume (VT) and respiratory quotient (RQ). The coefficients of
      variation for each variable for the 10 subjects were calculated. At rest, the
      90th centile variability for measured cardiopulmonary variables (RB only) was
      <35%. During exercise, the 90th centile for variability for measured
      cardiopulmonary variables for HME and RB were < or =20 and <40%, respectively.
      These measurements in healthy adults should inform sample size in research
      studies.

PMID- 17188946
TI  - Hydrophobic interaction expanded bed adsorption chromatography (HI-EBAC) based
      facile purification of recombinant streptokinase from E. coli inclusion bodies.
AB  - The downstream processing of recombinant streptokinase (rSK), a protein used for
      dissolution of blood clots has been investigated employing Escherichia coli
      inclusion bodies obtained after direct chemical extraction followed by expanded
      bed adsorption chromatography (EBAC). Streptokinase was over-expressed using high
      cell density (final OD(600)=40) culture of recombinant E. coli, and an SK protein
      concentration of 1080 mg l(-1) was achieved. The wet cell pellet after
      centrifugation was re-suspended in 8M urea containing buffer resulting in direct
      extraction of almost 97% of cellular proteins into solution. Compared to
      mechanical disruption using sonication, the direct extraction helped in
      simultaneous cell lysis and inclusion body (IB) solubilization in a single
      integrated step. The post-extraction solution containing cell debris and cellular
      proteins was diluted and directly loaded on to an EBAC column containing
      Streamline phenyl, without clarification. By passing the solution four times
      through the column and using 1M NaCl during loading, 82.7% rSK activity could be
      recovered in the 10mM sodium phosphate buffer used for elution. A 3-fold increase
      in specific activity of rSK, from 0.18 x 10(5) in cell lysate to 0.53 x 10(5)IU
      mg(-1) resulted after this step. rSK was further purified to near-homogeneity
      (specific activity=0.96 x 10(5)IU mg(-1)) by a subsequent ion-exchange step
      operated in packed bed mode. An overall downstream recovery of 63% rSK was
      achieved after EBAC and ion exchange chromatography. The paper thus describes the
      purification of rSK using a three-step regime involving simple, efficient and
      highly facile steps.

PMID- 17188947
TI  - Two-dimensional electrophoresis in proteome expression analysis.
AB  - Cell proteomes are complex, given they consist of several thousand proteins. Two
      dimensional electrophoresis (2DE) is unique not only for its ability to
      simultaneously separate thousands of proteins but also for detecting post- and co
      translational modifications, which cannot be predicted from genome sequences.
      This review will describe the protocols applied to prepare 2D gels properly, and
      analyse and summarise the major challenges for successful proteome analysis using
      2DE, i.e. the ability to analyse very alkaline, hydrophobic and/or low or high
      M(r) proteins with high resolution and the ability to detect minor components.
      Challenges involving sample preparation and solubilisation prior to the first
      dimension IEF/IPG step will be studied in depth. Sample preparation is crucial in
      2DE studies and greatly influences other stages of the technique. It is the aim
      of this review not only to describe the challenges and limitations of 2DE but
      also to suggest the avenues, the evolution, the potential and the future of 2DE
      in proteomics.

PMID- 17188948
TI  - Stir bar sorptive extraction and liquid chromatography with UV detection for
      determination of antidepressants in plasma samples.
AB  - A sensitive and reproducible stir bar sorptive extraction and liquid
      chromatography (SBSE/LC-UV) method is described for the determination of
      sertraline, mirtazapine, fluoxetine, citalopram, paroxetine, imipramine,
      nortriptyline, amitriptyne, and desipramine in plasma samples. Important factors
      in the optimization of SBSE efficiency are discussed, such as extraction time,
      pH, ionic strength, influence of plasma proteins, and desorption conditions:
      solvents, modes (magnetic stir, ultrasonic), time, and number of desorption
      steps. The SBSE/LC-UV method showed to be linear in a concentration ranging from
      the limit of quantification (LOQ) to 1000.0 ng mL(-1). The LOQ values ranged from
      10.0 ng mL(-1) to 40.0 ng mL(-1). The inter-day precision of the SBSE/LC-UV
      method presented coefficient of the variation lower than 15%. Based on figures of
      the merit results, the SBSE/LC-UV methodology showed to be adequate to the
      antidepressants analyses from therapeutic to toxic therapeutic levels. In order
      to evaluate the proposed method for clinical use, the SBSE/LC-UV method was
      applied to the analysis of plasma samples from elderly depressed patients.

PMID- 17188949
TI  - Self-assembly and structural characterization of Echinococcus granulosus antigen
      B recombinant subunit oligomers.
AB  - Echinococcus granulosus antigen B is an oligomeric protein of 120-160 kDa
      composed by 8-kDa (AgB8) subunits. Here, we demonstrated that the AgB8
      recombinant subunits AgB8/1, AgB8/2 and AgB8/3 are able to self-associate into
      high order homo-oligomers, showing similar properties to that of parasite
      produced AgB, making them valuable tools to study AgB structure. Dynamic light
      scattering, size exclusion chromatography and cross-linking assays revealed
      approximately 120- to 160-kDa recombinant oligomers, with a tendency to form
      populations with different aggregation states. Recombinant oligomers showed
      helical circular dichroism spectra and thermostability similar to those of
      purified AgB. Cross-linking and limited proteolysis experiments indicated
      different degrees of stability and compactness between the recombinant oligomers,
      with the AgB8/3 one showing a more stable and compact structure. We have also
      built AgB8 subunit structural models in order to predict the surfaces possibly
      involved in electrostatic and hydrophobic interactions during oligomerization.

PMID- 17188950
TI  - Toxicity of 6-thioguanine: no hepatotoxicity in a series of IBD patients treated
      with long-term, low dose 6-thioguanine. Some evidence for dose or metabolite
      level dependent effects?
AB  - BACKGROUND: 6-Thioguanine is used in inflammatory bowel disease since 2001, with
      promising short-term results. In 2003, liver histology of some 6-thioguanine
      treated patients showed nodular regenerative hyperplasia. Recently, magnetic
      resonance imaging revealed nodular regenerative hyperplasia in patients with
      normal histology. AIMS: Investigating the presence of nodular regenerative
      hyperplasia in long-term 6-thioguanine treated patients. PATIENTS AND METHODS:
      Inflammatory bowel disease patients, using 6-thioguanine minimally 24 months,
      were asked to undergo liver biopsy and magnetic resonance imaging. RESULTS:
      Fourteen patients used 6-thioguanine minimally 24 months, 13 participated. Mean 6
      thioguanine therapy duration, daily dose and 6-thioguanine nucleotide levels
      were: 36 months, 18.8 mg (0.28 mg/kg) and 705 pmol/8x10(8) erythrocytes,
      respectively. Liver histology and magnetic resonance imaging showed no nodular
      regenerative hyperplasia. DISCUSSION: Liver biopsy and magnetic resonance imaging
      showed no nodular regenerative hyperplasia in these long-term 6-thioguanine
      treated inflammatory bowel disease patients. 6-thioguanine dose and metabolite
      levels were lower compared with previous nodular regenerative hyperplasia
      reports, suggesting dose or metabolite level-dependent effects. Otherwise,
      nodular regenerative hyperplasia is related with inflammatory bowel disease
      itself and immunosuppressives, including azathioprine and 6-mercaptopurine.
      CONCLUSION: 6-Thioguanine is debated due to nodular regenerative hyperplasia. We
      found no nodular regenerative hyperplasia in inflammatory bowel disease patients
      with long-term, low dosed 6-thioguanine, suggesting metabolite level-dependent
      effects. Therefore, 6-thioguanine still seems useful, but in selected patients,
      intolerant for other immunosuppressives, low dosed and under close surveillance
      of metabolite levels and hepatotoxity.

PMID- 17188957
TI  - Hepatitis C: a new horizon.

PMID- 17188958
TI  - Shall we bury the sword? Imaging of hepatic fibrosis.

PMID- 17188951
TI  - Impaired posterior frontal sutural fusion in the biglycan/decorin double
      deficient mice.
AB  - Biglycan (Bgn) and decorin (Dcn) are highly expressed in numerous tissues in the
      craniofacial complex. However, their expression and function in the cranial
      sutures are unknown. In order to study this, we first examined the expression of
      biglycan and decorin in the posterior frontal suture (PFS), which predictably
      fuses between 21 and 45 days post-natal and in the non-fusing sagittal (S) suture
      from wild-type (Wt) mice. Our data showed that Bgn and Dcn were expressed in both
      cranial sutures. We then characterized the cranial suture phenotype in Bgn
      deficient, Dcn deficient, Bgn/Dcn double deficient, and Wt mice. At embryonic day
      18.5, alizarin red/alcian blue staining showed that the Bgn/Dcn double deficient
      mice had hypomineralization of the frontal and parietal craniofacial bones.
      Histological analysis of adult mice (45-60 days post-natal) showed that the Bgn
      or Dcn deficient mice had no cranial suture abnormalities and
      immunohistochemistry staining showed increased production of Dcn in the PFS from
      Bgn deficient mice. To test possible compensation of Dcn in the Bgn deficient
      sutures, we examined the Bgn/Dcn double deficient mice and found that they had
      impaired fusion of the PFS. Semi-quantitative RT-PCR analysis of RNA from 35 day
      old mice revealed increased expression of Bmp-4 and Dlx-5 in the PFS compared to
      their non-fusing S suture in Wt tissues and decreased expression of Dlx-5 in both
      PF and S sutures in the Bgn/Dcn double deficient mice compared to the Wt mice.
      Failure of PFS fusion and hypomineralization of the calvaria in the Bgn/Dcn
      double deficient mice demonstrates that these extracellular matrix proteoglycans
      could have a role in controlling the formation and growth of the cranial vault.

PMID- 17188959
TI  - Yield of advanced adenoma and cancer based on polyp size detected at screening
      flexible sigmoidoscopy.
AB  - BACKGROUND & AIMS: Observational screening of the colon with subsequent referral
      for colonoscopy raises questions about the threshold of polyp size that
      necessitates referral. To examine the yield at colonoscopy when a given size
      lesion is observed, we assessed the yield of advanced adenoma and cancer at
      colonoscopy based on the size of the abnormality detected at flexible
      sigmoidoscopy (FSG). METHODS: We used data from the Prostate, Lung, Colorectal,
      and Ovarian Cancer Screening Trial, a randomized, controlled, community-based
      study of FSG. RESULTS: Subsequent colonoscopy was performed on 10,850 subjects
      (60.4% male; mean age, 62.9 years) with a polyp visualized on screening FSG. For
      women with a polyp 0.5-0.9 cm on FSG (n = 1426), the yield in the distal colon on
      colonoscopy was 0.6% for cancer (number needed to screen [NNS] = 166) and 14.5%
      for advanced adenoma (NNS = 7). In men (n = 2183), the yield was 0.7% (NNS = 142)
      for cancer and 15.9% (NNS = 6) for advanced adenoma. Among persons with polyps
      0.5-0.9 cm identified on FSG, 5.5% (198/3609) had distal advanced adenomas that
      measured <1.0 cm but had villous histology or high-grade dysplasia, and 9.9%
      (357/3609) had adenomas > or =1 cm. CONCLUSIONS: The yield for a distal advanced
      adenomatous lesion when a polyp 0.5-0.9 cm is observed at FSG is substantial and
      is due to the presence of advanced histology in polyps <1 cm and to detection of
      polyps that measure > or =1.0 cm on colonoscopy. Establishing thresholds for
      observation versus evaluation will require careful assessment of the overall
      yield.

PMID- 17188960
TI  - Neuroimaging of the brain-gut axis: from basic understanding to treatment of
      functional GI disorders.

PMID- 17188962
TI  - Is the demonstration of adenoma reduction with rofecoxib a pyrrhic victory?

PMID- 17188963
TI  - Colon cancer screening, polyp size, and CT colonography: making sense of it all?

PMID- 17188964
TI  - Probiotics in inflammatory bowel disease: yet another mechanism of action?

PMID- 17188967
TI  - Eosinophilic esophagitis: new insights into an emerging disease.

PMID- 17188965
TI  - Screening colonoscopy: the benefits are durable, but are they as great as we
      thought?

PMID- 17188968
TI  - Making sense of CT colonography-related complication rates.

PMID- 17188970
TI  - Increased expression of hepcidin in obese patients: impact on phenotypic
      expression of hemochromatosis and pathophysiology of dysmetabolic iron overload
      syndrome.

PMID- 17188972
TI  - Early repolarization variant: interesting electrocardiographic anomaly or marker
      of arrhythmogenic risk?

PMID- 17188973
TI  - The burden of nonischemic ST-segment elevation.

PMID- 17188974
TI  - Variation in ST-segment elevation in early repolarization.

PMID- 17188975
TI  - The hyperkalemic Brugada sign.
AB  - BACKGROUND: A few case reports have indicated that hyperkalemia can induce a
      Brugada pattern in the electrocardiogram. The specific clinical and
      electrocardiographic features of the hyperkalemic Brugada sign, however, have not
      been previously described. METHODS: A case series was collected from hospitalized
      hyperkalemic patients with a type I Brugada pattern in the electrocardiogram, and
      a literature review was performed. Electrocardiograms were examined for rhythm
      and morphology, and clinical characteristics were analyzed. RESULTS: Nine new
      cases with the hyperkalemic Brugada sign were identified with an additional 15
      cases found in the literature. Of the 9 cases, 8 were male patients, and all were
      critically ill; 5 of the 9 died within 48 hours. The mean (+/-SD) serum potassium
      level was 7.8 +/- 0.5 mEq/L. The mean QRS width was 144 +/- 31 milliseconds, and
      all had abnormal QRS axis. In 6 cases, there was a wide complex rhythm without
      visible P waves. The clinical and electrocardiographic characteristics of 15
      cases found in the literature were remarkably similar to those in our series.
      CONCLUSIONS: The hyperkalemic Brugada pattern differs in substantial ways from
      the electrocardiogram of patients with the genetic Brugada syndrome. Many
      patients have wide complex rhythms without visible P waves, marked QRS widening,
      and an abnormal QRS axis. Most patients are male, and many are critically ill.
      Prompt recognition of this clinical and electrocardiographic entity may expedite
      the initiation of appropriate treatment for hyperkalemia.

PMID- 17188976
TI  - Location of Q-wave myocardial infarction in the era of cardiac magnetic resonance
      imaging techniques: an update.

PMID- 17189009
TI  - Developing country trialists are key for malaria vaccine goals.

PMID- 17189010
TI  - Oklahoma, OK: emergency preparedness in the USA.

PMID- 17189011
TI  - Kofi Annan's positive legacy for health.

PMID- 17189013
TI  - Medical response to the 2005 terrorist bombings in London.

PMID- 17189012
TI  - Poverty, death, and a future influenza pandemic.

PMID- 17189014
TI  - Prion reduction filters.

PMID- 17189015
TI  - Haemoglobin concentrations in chronic kidney disease.

PMID- 17189016
TI  - Dengue: setting the global research agenda.

PMID- 17189017
TI  - Paracetamol: are therapeutic doses entirely safe?

PMID- 17189018
TI  - Health reform in Chile.

PMID- 17189019
TI  - Iain Chalmers: maverick master of medical evidence.

PMID- 17189020
TI  - Risk in drug trials.

PMID- 17189021
TI  - Risk in drug trials.

PMID- 17189022
TI  - Risk in drug trials.

PMID- 17189023
TI  - TGN1412 and The Lancet's solicitation of reports of phase I trials.

PMID- 17189024
TI  - Risk in drug trials.

PMID- 17189025
TI  - Mortality of HIV-infected patients in low-income countries.

PMID- 17189027
TI  - Varicella vaccine: local convenience or global equity?

PMID- 17189028
TI  - Varicella in immunocompromised patients.

PMID- 17189029
TI  - Safety and immunogenicity of H5N1 vaccine.

PMID- 17189030
TI  - Payments for health care in India.

PMID- 17189031
TI  - Suboptimum use of FDA drug advisory committees.

PMID- 17189032
TI  - Estimation of potential global pandemic influenza mortality on the basis of vital
      registry data from the 1918-20 pandemic: a quantitative analysis.
AB  - BACKGROUND: The threat of an avian influenza pandemic is causing widespread
      public concern and health policy response, especially in high-income countries.
      Our aim was to use high-quality vital registration data gathered during the 1918
      20 pandemic to estimate global mortality should such a pandemic occur today.
      METHODS: We identified all countries with high-quality vital registration data
      for the 1918-20 pandemic and used these data to calculate excess mortality. We
      developed ordinary least squares regression models that related excess mortality
      to per-head income and absolute latitude and used these models to estimate
      mortality had there been an influenza pandemic in 2004. FINDINGS: Excess
      mortality data show that, even in 1918-20, population mortality varied over 30
      fold across countries. Per-head income explained a large fraction of this
      variation in mortality. Extrapolation of 1918-20 mortality rates to the worldwide
      population of 2004 indicates that an estimated 62 million people (10th-90th
      percentile range 51 million-81 million) would be killed by a similar influenza
      pandemic; 96% (95% CI 95-98) of these deaths would occur in the developing world.
      If this mortality were concentrated in a single year, it would increase global
      mortality by 114%. INTERPRETATION: This analysis of the empirical record of the
      1918-20 pandemic provides a plausible upper bound on pandemic mortality. Most
      deaths will occur in poor countries--ie, in societies whose scarce health
      resources are already stretched by existing health priorities.

PMID- 17189034
TI  - Reduction in infectivity of endogenous transmissible spongiform encephalopathies
      present in blood by adsorption to selective affinity resins.
AB  - BACKGROUND: Transmissible spongiform encephalopathies (TSE) can be contracted
      through blood transfusion. Selective adsorption of the causative agent from
      donated blood might be one of the best ways of managing this risk. In our study,
      affinity resin L13, which reduces brain-derived infectivity spiked into human red
      blood cell concentrate by around 4 log(10)ID(50), and its equivalent, L13A,
      produced on a manufacturing scale, were assessed for their ability to remove TSE
      infectivity endogenously present in blood. METHODS: 500 mL of scrapie-infected
      hamster whole blood was leucoreduced at full scale before passage through the
      affinity resins. Infectivity of whole blood, leucoreduced whole blood
      (challenge), and the recovered blood from each flow-through was measured by
      limiting dilution titration. FINDINGS: Leucoreduction removed 72% of input
      infectivity. 15 of 99 animals were infected by the challenge, whereas none of the
      96 or 100 animals inoculated with the final flow-throughs from either resin
      developed the disease after 540 days. The limit of detection of the bioassay was
      0.2 infectious doses per mL. The overall reduction of the challenge infectivity
      was more than 1.22 log10ID. The results showed removal of endogenous TSE
      infectivity from leucoreduced whole blood by affinity ligands. The same resins
      adsorb normal and abnormal prion protein from human infections with variant,
      sporadic, and familial Creutzfeldt-Jakob disease, in the presence of blood
      components. INTERPRETATION: TSE affinity ligands, when incorporated into
      appropriate devices, can be used to mitigate the risks from TSE-infected blood,
      blood products, and other materials exposed to TSE infectivity.

PMID- 17189033
TI  - Reduction in critical mortality in urban mass casualty incidents: analysis of
      triage, surge, and resource use after the London bombings on July 7, 2005.
AB  - BACKGROUND: The terrorist bombings in London on July 7, 2005, produced the
      largest mass casualty event in the UK since World War 2. The aim of this study
      was to analyse the prehospital and in-hospital response to the incident and
      identify system processes that optimise resource use and reduce critical
      mortality. METHODS: This study was a retrospective analysis of the London-wide
      prehospital response and the in-hospital response of one academic trauma centre.
      Data for injuries, outcome, triage, patient flow, and resource use were obtained
      by the review of emergency services and hospital records. FINDINGS: There were
      775 casualties and 56 deaths, 53 at scene. 55 patients were triaged to priority
      dispatch and 20 patients were critically injured. Critical mortality was low at
      15% and not due to poor availability of resources. Over-triage rates were reduced
      where advanced prehospital teams did initial scene triage. The Royal London
      Hospital received 194 casualties, 27 arrived as seriously injured. Maximum surge
      rate was 18 seriously injured patients per hour and resuscitation room capacity
      was reached within 15 min. 17 patients needed surgery and 264 units of blood
      products were used in the first 15 h, close to the hospital's routine daily blood
      use. INTERPRETATION: Critical mortality was reduced by rapid advanced major
      incident management and seems unrelated to over-triage. Hospital surge capacity
      can be maintained by repeated effective triage and implementing a hospital-wide
      damage control philosophy, keeping investigations to a minimum, and transferring
      patients rapidly to definitive care.

PMID- 17189037
TI  - Is Burkitt's lymphoma sexy enough?

PMID- 17189036
TI  - Reducing inequalities from injuries in Europe.
AB  - Injuries cause 9% of deaths and 14% of ill health in the WHO European Region.
      This problem is neglected; injuries are often seen as part of everyday life.
      However, although western Europe has good safety levels, death and disability
      from injury are rising in eastern Europe. People in low-to-middle-income
      countries in the Region are 3.6 times more likely to die from injuries than those
      in high-income countries. Economic and political change have led to unemployment,
      income inequalities, increased traffic, reduced restrictions on alcohol, and loss
      of social support. Risks such as movement of vulnerable populations and transfer
      of lifestyles and products between countries also need attention. In many
      countries, the public-health response has been inadequate, yet the cost is
      devastating to individuals and health-service budgets. More than half a million
      lives could be saved annually in the Region if recent knowledge could be used to
      prevent injuries and thus redress social injustice in this area.

PMID- 17189035
TI  - Alcohol abuse in the critically ill patient.
AB  - Alcohol abuse and dependence disorders are common in the 10% of hospitalised
      patients who need admission to the intensive care unit (ICU), but these disorders
      are often undiagnosed. The systemic effects from the excessive use of alcohol
      increase susceptibility to, or directly cause various important disorders in the
      critically ill. Early recognition of alcohol abuse and dependence is necessary
      and should prompt consideration of several alcohol-specific diagnoses that have
      important prognostic and therapeutic implications for these patients. We discuss
      the use of screening tests to improve the identification of alcohol abuse and
      dependence disorders, the epidemiology and pathogenesis of important alcohol
      related disorders, differences in the presentation of several common alcohol
      related diagnoses in the ICU, and important alcohol-specific therapies.

PMID- 17189038
TI  - Poverty and user fees for public health care in low-income countries: lessons
      from Uganda and Cambodia.

PMID- 17189039
TI  - Dementia and white-matter demyelination in young patient with neurosyphilis.

PMID- 17189040
TI  - Excerpts from the United States Renal Data System 2006 Annual Data Report.

PMID- 17189042
TI  - A pioneer in the development of modern ultrasound: Robert William Boyle (1883
      1955).
AB  - Robert William Boyle was one of the pioneers in the development and application
      of ultrasound. His remarkable career has not been previously traced in any depth,
      nor have his contributions, especially those during WWI, been carefully
      described. In collaboration with Lord Rutherford, his work on the development of
      ultrasound methods for submarine detection paralleled those in France under Paul
      Langevin (1872-1946), who many consider to be the father of modern ultrasound.
      This biographic account of Boyle's life focuses on his ultrasound research
      contributions, particularly the developments during WWI and those in the 10 years
      after. Evidence is presented that his pioneering research, along with that of
      Langevin, provided much of the foundation for modern ultrasound developments.
      Although this paper is partially based on somewhat dispersed biographic
      information performed by others, original letters and research papers, in
      addition to records and verbal accounts provided by relatives, have been used and
      consulted.

PMID- 17189043
TI  - Transcranial brain parenchyma sonography in movement disorders: state of the art.
AB  - The present paper summarizes recommendations on transcranial sonography (TCS)
      application in neurodegenerative diseases, resulting from a consensus meeting of
      the European Society of Neurosonology and Cerebral Hemodynamics. TCS of distinct
      infra- and supratentorial brain structures detects characteristic changes in
      several movement disorders, such as abnormal hyperechogenicity of substantia
      nigra (SN) in Parkinson's disease and of lenticular nucleus in dystonia, Wilson's
      disease and atypical Parkinsonian disorders. In healthy adults, the TCS finding
      of marked SN hyperechogenicity indicates a subclinical functional impairment of
      the nigrostriatal dopaminergic system. The finding of marked SN hyperechogenicity
      in combination with normal lenticular-nucleus echogenicity discriminates
      idiopathic Parkinson's disease from multiple-system atrophy and progressive
      supranuclear palsy with a positive predictive value of more than 90%. As TCS is a
      quick and noninvasive method, using the same duplex-ultrasound machines as for
      investigation of intracranial vessels, applicable even in agitated patients, this
      method has a great potential to be more widely used.

PMID- 17189044
TI  - Computer-aided diagnosis of carotid atherosclerosis based on ultrasound image
      statistics, laws' texture and neural networks.
AB  - Quantitative characterisation of carotid atherosclerosis and classification into
      symptomatic or asymptomatic is crucial in planning optimal treatment of
      atheromatous plaque. The computer-aided diagnosis (CAD) system described in this
      paper can analyse ultrasound (US) images of carotid artery and classify them into
      symptomatic or asymptomatic based on their echogenicity characteristics. The CAD
      system consists of three modules: a) the feature extraction module, where first
      order statistical (FOS) features and Laws' texture energy can be estimated, b)
      the dimensionality reduction module, where the number of features can be reduced
      using analysis of variance (ANOVA), and c) the classifier module consisting of a
      neural network (NN) trained by a novel hybrid method based on genetic algorithms
      (GAs) along with the back propagation algorithm. The hybrid method is able to
      select the most robust features, to adjust automatically the NN architecture and
      to optimise the classification performance. The performance is measured by the
      accuracy, sensitivity, specificity and the area under the receiver-operating
      characteristic (ROC) curve. The CAD design and development is based on images
      from 54 symptomatic and 54 asymptomatic plaques. This study demonstrates the
      ability of a CAD system based on US image analysis and a hybrid trained NN to
      identify atheromatous plaques at high risk of stroke.

PMID- 17189045
TI  - In-vivo evaluation of convex array synthetic aperture imaging.
AB  - This paper presents an in-vivo study of synthetic transmit aperture (STA) imaging
      in comparison with conventional imaging, evaluating whether STA imaging is
      feasible in-vivo and whether the image quality obtained is comparable with
      traditional scanned imaging in terms of penetration depth, spatial resolution,
      contrast resolution and artifacts. Acquisition was performed using our research
      scanner RASMUS and a 5.5 MHz convex array transducer. STA imaging was acquired
      using circular wave emulation by 33-element subapertures and a 20 micros linear
      FM signal as excitation pulse. For conventional imaging, a 64 element aperture
      was used in transmit and receive with a 1.5 cycle sinusoid excitation pulse.
      Conventional and STA images were acquired interleaved, ensuring that the exact
      same anatomical location was scanned. Image sequences were recorded in real time
      and processed off-line. Seven male volunteers were scanned abdominally and the
      resulting images were compared by three medical doctors using randomized blinded
      presentation. Penetration and image quality were scored and evaluated
      statistically. Results showed slightly but significantly (0.48 cm, p = 0.008)
      increased penetration using STA. Image quality was also highly significantly (p <
      0.001) increased. Results show that in-vivo ultrasound imaging using STA is
      feasible for abdominal imaging without severe motion artifacts.

PMID- 17189046
TI  - Improvement of elastographic displacement estimation using a two-step cross
      correlation method.
AB  - The cross-correlation algorithm used to compute the local strain components for
      elastographic imaging requires a minimum radio-frequency data segment length of
      around 10 wavelengths to obtain accurate and precise strain estimates with a
      reasonable signal-to-noise ratio. Shorter radio-frequency data segments generally
      introduce increased estimation errors as the information content in the data
      segment reduces. However, shorter data segments and increased overlaps are
      essential to improve the axial resolution in the strain image. In this paper, we
      propose a two-step cross-correlation technique that enables the use of window
      lengths on the order of a single wavelength to provide displacement and strain
      estimates with similar noise properties as those obtained with a 10 wavelength
      window. The first processing step utilizes a window length on the order of 10
      wavelengths to obtain coarse displacement estimates between the pre- and post
      compression radio frequency data frames. This coarse displacement is then
      interpolated and utilized as the initial guess-estimate for the second cross
      correlation processing step using the smaller window. This step utilizes a single
      wavelength window to improve the axial resolution in strain estimation, without
      significantly compromising the noise properties of the image. Simulation and
      experimental results show that the signal-to-noise and contrast-to-noise ratio
      estimates improve significantly at the smaller window lengths with the two-step
      processing when compared with the use of a similar sized window in the currently
      utilized single window method.

PMID- 17189048
TI  - Comparison of nonuniform rotational distortion between mechanical IVUS and OCT
      using a phantom model.
AB  - Optical coherence tomography (OCT) is an optical analog of mechanical
      intravascular ultrasound (M-IVUS) with much higher spatial resolution. However,
      no data exist regarding the nonuniform rotational distortion (NURD) with OCT. The
      aim of the study was to investigate whether OCT generates less NURD relative to M
      IVUS. A coronary artery phantom model was constructed with a rubber ring (3.68 mm
      in diameter), located at the distal end of the phantom. This model was also
      composed of eight equally spaced steel wires and an additional marker-wire. Two
      types of vascular phantoms were used, mild curve (90 degrees ) and acute curve
      (near 180 degrees ). Subsequent M-IVUS (n = 6) and OCT (n = 6) imaging was
      performed. Eight angles between eight wires, except the marker-wire, were
      measured from each image. These angles, measured with M-IVUS and OCT, were
      compared with those of high-resolution optical photography as a gold standard.
      The average in angle differences was significantly smaller in OCT compared with M
      IVUS in the mild curve model (3.2 +/- 1.0 degrees vs, 6.9 +/- 2.1 degrees , p <
      0.01). Compared with the latter model, the average in angle differences was
      exaggerated in the acute curve model with M-IVUS (9.1 +/- 0.9 degrees vs. 6.9 +/-
      2.1 degrees , p < 0.05) but not with OCT (3.5 +/- 0.8 degrees vs. 3.2 +/- 1.0
      degrees , p= not significant). OCT generates significantly less NURD compared
      with M-IVUS, especially in tortuous situation.

PMID- 17189047
TI  - Normal and shear strain estimation using beam steering on linear-array
      transducers.
AB  - In current ultrasound elastography, only the axial component of the displacement
      vector is estimated and used to produce strain images. A method was recently
      proposed by our group to estimate both the axial and lateral components of a
      displacement vector following a uniaxial compression. Previous work evaluated the
      technique using both simulations and a mechanically translated phased array
      transducer. In this paper, we present initial results using beam steering on a
      linear array transducer attached to a commercial scanner to acquire echo signals
      for estimating 2-D displacement vectors. Single-inclusion and anthropomorphic
      breast phantoms with different boundary properties between the inclusion and
      background material are imaged by acquiring echo data along beam lines ranging
      from -15 degrees to 15 degrees relative to the compression direction. 1-D cross
      correlation is used to calculate "angular displacements" in each acquisition
      direction, yielding axial and lateral components of the displacement vector.
      Strain tensor components are estimated from these displacements. Features on
      shear strain images generated for the inclusion phantom agree with those
      predicted using FEA analysis. Experimental results demonstrate the utility of
      this technique on clinical scanners. Shear strain tensors obtained using this
      method may provide useful information for the differentiation of benign from
      malignant tumors. For the linear array transducer used in this study, the optimum
      angular increment is around 3 degrees. However, more work is required for the
      selection of an appropriate value for the maximum beam angle for optimal
      performance of this technique.

PMID- 17189049
TI  - Error analysis of ultrasonic tissue doppler velocity estimation techniques for
      quantification of velocity and strain.
AB  - Recent work in the field of Doppler tissue imaging has focused mainly on the
      quantification of results involving the use of techniques of strain and strain
      rate imaging. These results are based on measuring a velocity gradient between
      two points, a known distance apart, in the region-of-interest. Although many
      recent publications have demonstrated the potential of this technique in clinical
      terms, the method still suffers from low repeatability. The work presented here
      demonstrates, through the use of a rotating phantom arrangement and a custom
      developed single element ultrasound system, that this is a consequence of the
      fundamental accuracy of the technique used to estimate the original velocities.
      Results are presented comparing the performance of the conventional Kasai
      autocorrelation velocity estimator with those obtained using time domain cross
      correlation and the complex cross-correlation model based estimator. The results
      demonstrate that the complex cross-correlation model based technique is able to
      offer lower standard deviations of the velocity gradient estimations compared
      with the Kasai algorithm.

PMID- 17189050
TI  - Monitoring imaging of lesions induced by high intensity focused ultrasound based
      on differential ultrasonic attenuation and integrated backscatter estimation.
AB  - We investigated the feasibility of two monitoring imaging methods to visualize
      and evaluate the high intensity focused ultrasound (HIFU) induced lesions in
      vitro during and after their formation, which were based on differential
      ultrasonic parameter estimation. Firstly, ultrasonic attenuation slope of tissue
      sample was estimated based on the spectral analysis of ultrasound RF
      backscattered signals. The differential attenuation slope maps were acquired,
      which were interpreted as the differences between the pretreatment image and
      those obtained in different stages during HIFU therapy. Secondly, ultrasonic
      integrated backscatter (IBS), defined as the frequency average of the backscatter
      transfer function over the useful bandwidth, was proposed quantitatively to
      evaluate the extent of lesions with the same RF signals as the first method.
      Differential IBS maps were also acquired to visualize temporal evolution of
      lesion formation. It was found in pig liver in vitro that more precise definition
      of the treated area was obtained from the differential IBS images than from
      differential attenuation slope images. Dramatic increase in both attenuation and
      IBS value was observed during the therapy, which may be related to dramatic
      enhancement of cavitation due to boiling and accompanying tissue damage. Two
      methods to obtain one differential image were compared and the cumulative
      differential image was found to be able to eliminate noises and artifacts to some
      extent, which was the cumulation of a series of differential images acquired from
      the differences between the temporally adjacent RF data frames. Moreover, we
      presented a bidirectional color code for identification of the artifacts due to
      tissue movements caused by HIFU radiation force. We conclude that cumulative
      differential IBS images have the potential to monitor the formation of HIFU
      induced lesions.

PMID- 17189051
TI  - Noninvasive, transcranial and localized opening of the blood-brain barrier using
      focused ultrasound in mice.
AB  - The feasibility of blood-brain barrier (BBB) opening in the hippocampus of wild
      type mice using focused ultrasound (FUS) through the intact skull and skin was
      investigated. Needle hydrophone measurements through ex vivo skulls revealed
      minimal attenuation ( approximately 18% of the pressure amplitude), a well
      focused beam pattern and minute focus displacement through the parietal bone. In
      experiments in vivo, the brains of three mice were sonicated transcranially.
      Pulsed ultrasound sonications at 1.5 MHz and acoustic pressures ranging from 0.8
      to 2.7 MPa were used at 20% duty cycle. Before sonication, a bolus of 10 microL
      of an ultrasound contrast agents (Optison) was injected intravenously. Contrast
      enhanced high-resolution magnetic resonance imaging (9.4 T) revealed BBB opening
      and allowed for the monitoring of the slow permeation of gadolinium in the
      hippocampus. The region of the brain where BBB opening occurred increased with
      the pressure amplitude. These findings thus demonstrated the feasibility of
      locally opening the BBB in mice using FUS through intact skull and skin and serve
      as the first step in determining and assessing feasibility of drug delivery to
      specific regions in the mouse brain using FUS.

PMID- 17189052
TI  - High intensity ultrasound clamp for bloodless partial nephrectomy: In vitro and
      in vivo experiments.
AB  - In some patients at risk of disease recurrence of renal cancers, maximum
      conservation of the kidney is possible through partial nephrectomy. However,
      bloodless surgery is difficult to achieve. The article describes an ultrasonic
      clamp, which optimises energy deposition and monitors lesion development with an
      echo-based technique. Using this novel apparatus, coagulation necroses have been
      obtained in vitro on substantial thicknesses (23 to 38 mm) over exposure
      durations ranging from 10 s to 130 s, and with acoustic intensities of less than
      15 W/cm(2) per transducer. When used for coagulation purposes, two transducers
      situated on opposite arms of the clamp are driven, while for monitoring, only one
      is used. Lesions are monitored in real time by analysing the echo signal returned
      by the opposite arm of the clamp. The presence of a lesion is evaluated on the
      basis of energy changes and echo phase as a function of time. Both kidneys of two
      pigs (30 to 36 mm thick) were treated in vivo with the clamp, and the partial
      nephrectomies performed proved to be bloodless.

PMID- 17189053
TI  - Image-guided acoustic hemostasis for hemorrhage in the posterior liver.
AB  - We investigated the use of ultrasound image-guided high intensity focused
      ultrasound (HIFU) to stop bleeding from injuries in the posterior liver. A HIFU
      transducer with focal length of 3.5 cm and frequency of 3.2 MHz was integrated
      with an intraoperative high-resolution ultrasound-imaging probe. Wedge tissue
      extractions, 30-mm long, 5-mm wide and 8-mm deep, were made in the posterior
      liver surface of five pigs to induce bleeding. The device was positioned on the
      anterior surface of the liver and HIFU was applied using ultrasound image
      guidance. Hemostasis was achieved in 66 +/- 18 s (mean +/- standard deviation)
      for 17 HIFU treatments. During 7 min of sham HIFU treatment, none of the control
      incisions (n = 7) became hemostatic. Ultrasound image-guided HIFU offers a
      promising method for hemostasis in surgical settings in which the hemorrhage site
      is hidden and/or not accessible.

PMID- 17189054
TI  - Relative transmissivity of ultrasound coupling agents commonly used by therapists
      in the UK.
AB  - Coupling agents are required when using therapeutic ultrasound (US) to maximize
      acoustic contact between the transducer and the insonated tissue. US beam power
      is attenuated to varying extents by different couplants and this may influence
      treatment efficacy, since therapeutic effects are dose-dependent. It is therefore
      important to know how well different couplants transmit US. In this study, the
      transmission characteristics of a range of gel couplants were measured using a
      radiation force balance. Data were collected for gels commonly used by UK
      therapists and at the powers and frequencies advocated for low-intensity
      therapeutic practice. Transmissivities of standard couplants relative to degassed
      water varied between 95% and 108% (nominal 95% confidence intervals between 0%
      and 11%). The spread and ranking of transmissivities changed when the US
      frequency was varied. For clinical purposes, however, there was no significant
      difference between transmissivities of the gels under test.

PMID- 17189055
TI  - An in vivo rat model simulating imaging of human kidney by diagnostic ultrasound
      with gas-body contrast agent.
AB  - One kidney of anesthetized rats was imaged by diagnostic ultrasound with contrast
      agent under conditions simulating both the geometry and the attenuation
      encountered during human perfusion imaging. Contrary to earlier predictions,
      glomerular capillary rupture with blood loss into Bowman's space and proximal
      tubules occurred in our clinically relevant model system. Quantitative analysis
      of histologic sections showed that 37 +/- 5% of the glomeruli at the center of
      the scan plane had blood cells in Bowman's space after imaging for 1 min with 1.8
      MPa (mechanical index equivalent, MIe = 1.5) with a 1 s image trigger interval
      during IV injection of 10 microl/kg/min of Definity contrast agent (as
      recommended by the manufacturer). This percentage decreased rapidly with
      decreasing peak rarefactional pressure amplitude to an apparent threshold of 0.73
      MPa (MIe = 0.6). The percentage of glomeruli with hemorrhage decreased in
      proportion to dose when reduced below the recommended value, but leveled-off at
      doses above it. The percentage of glomerular hemorrhage increased with increasing
      numbers of image exposures, with an initial rate of 1.1% per image. The
      glomerular hemorrhage also depended on the frame trigger interval with no
      hemorrhage evident for continuous imaging but a maximal effect for trigger
      intervals greater than about 1 s. These results indicated that there is a
      potential for clinical diagnostic ultrasound with contrast agent to induce
      glomerular hemorrhage.

PMID- 17189056
TI  - Interaction of transthoracic ultrasound and intravenous microbubbles with cardiac
      mechanoreceptors.
AB  - The purpose of this study was to examine the effect of transthoracic ultrasound
      (TTU) and intravenous microbubbles (MB) on cardiac mechanoreceptors. In 16
      rabbits (eight normal and eight chronic heart failure), renal sympathetic nerve
      activity (RSNA), heart rate and mean arterial pressure were examined before,
      during and after 1 MHz TTU at different peak negative pressures (0.12 to 0.43
      MPa) and duty cycles in the presence and absence of perfluorocarbon MB. TTU
      applications were for 10 s, and the overall duration of MB infusion was
      approximately 60 s for each setting. TTU without MB had no effect on any
      parameter. During the microbubble infusion, however, TTU at higher peak negative
      pressures (> or =0.27 MPa) and 100% duty cycle resulted in a consistent decrease
      in RSNA(-41 +/- 41% p < 0.001). This was accompanied by brief reflex reductions
      in mean arterial pressure and heart rate. The changes in RSNA induced by TTU and
      MB in all rabbits were abolished by vagotomy. TTU, in the presence of MB,
      stimulates mechanoreceptors in the heart reflexively to reduce RSNA.

PMID- 17189057
TI  - Proliferation and viability of adherent cells manipulated by standing-wave
      ultrasound in a microfluidic chip.
AB  - Ultrasonic-standing-wave (USW) technology has potential to become a standard
      method for gentle and contactless cell handling in microfluidic chips. We
      investigate the viability of adherent cells exposed to USWs by studying the
      proliferation rate of recultured cells following ultrasonic trapping and
      aggregation of low cell numbers in a microfluidic chip. The cells form 2-D
      aggregates inside the chip and the aggregates are held against a continuous flow
      of cell culture medium perpendicular to the propagation direction of the standing
      wave. No deviations in the doubling time from expected values (24 to 48 h) were
      observed for COS-7 cells held in the trap at acoustic pressure amplitudes up to
      0.85 MPa and for times ranging between 30 and 75 min. Thus, the results
      demonstrate the potential of ultrasonic standing waves as a tool for gentle
      manipulation of low cell numbers in microfluidic systems.

PMID- 17189058
TI  - Tracking a 3-D ultrasound probe with constantly visible fiducials.
AB  - A new method is presented for tracking a 3-D ultrasound (US) probe in space. The
      key is to use small fiducials that create point features in the US volume near
      the probe face and which are connected rigidly to the tracker on the probe. In
      this way, fiducials appear in every US volume and are used to calculate the
      position and orientation of the volume with respect to a fixed base. The main
      novelty is the elimination of a separate calibration device because calibration
      can be considered to be performed on every volume. After acquisition, the user
      simply marks the locations of the fiducials in the volume and solves a single
      equation to convert volume coordinates to the base. The point accuracy of the new
      method is slightly lower than those of conventional methods mainly because of the
      suboptimal appearance of the fiducials near the top of the image and little data
      averaging, but ease of use is improved.

PMID- 17189059
TI  - Effect of ultrasound-activated microbubbles on the cell electrophysiological
      properties.
AB  - New clinical applications of ultrasound contrast microbubbles extend beyond
      imaging and diagnosis toward therapeutic applications. Cell membrane permeability
      and the uptake of substances have been shown to be enhanced by microbubbles under
      ultrasound stimulation. However, the mechanisms of action of ultrasound-activated
      microbubbles are still unknown. The aim of our study was to examine how
      microbubbles and ultrasound interact with cells in an attempt to understand the
      sonoporation mechanism. The ruptured-patch-clamp whole-cell technique was used to
      measure membrane potential variations of a single cell. SonoVue microbubbles and
      mammary breast cancer cell line MDA-MB-231 were used. Ultrasound was applied
      using single-element transducers of 1 MHz. Microbubbles and cells were
      simultaneously video monitored during ultrasound exposure. Our results showed
      that, during sonoporation, a marked cell membrane hyperpolarization occurs (n = 6
      cells) at negative pressures above 150 kPa, indicating the activation of specific
      ion channels while the cell and the microbubbles remain viable. The
      hyperpolarization was sustained for as long as the microbubbles are in a direct
      contact with the cell and the ultrasound waves are transmitted. Smaller acoustic
      amplitudes induced only mild hyperpolarization, whereas shutting off the
      ultrasound brings the cell membrane potential to its resting value. However,
      ultrasound alone did not affect the cell membrane potential. A similar
      hyperpolarization of the cell membrane was observed when a mechanical pressure
      was applied on the cell through a glass probe. In conclusion, the results
      demonstrate that microbubbles' oscillations under ultrasound activation entail
      modifications of the electrophysiologic cell activities by triggering the
      modulation of ionic transports through the plasmic cell membrane. However, only
      cells in direct contact with the microbubbles are impacted. The mechanisms
      involved are likely related to activation of specific channels sensitive to
      mechanical stresses (stretch-activated channels) and possibly nonspecific ion
      channels.

PMID- 17189060
TI  - Frequency and pressure dependent attenuation and scattering by microbubbles.
AB  - The aim of this study was to evaluate experimentally the degree of pressure
      dependence of attenuation and scattering by microbubbles at low acoustic
      pressures with an empirical nonlinear model. In addition, the pressure dependency
      over a range of frequencies (1 to 5 MHz) has been studied. A series of
      transmission and scattering measurements were made with the microbubble SonoVue,
      using an automated system. Results show that, within the pressure range studied,
      attenuation as a result of the microbubble is pressure-dependent, whereas no such
      dependence of scattering was detectable. The pressure dependence of attenuation
      for SonoVue was found to be most significant at 1.5 MHz. The scattering is shown
      to be the highest at the lowest insonation frequency, around 1 approximately 1.25
      MHz, and then decreases with frequency.

PMID- 17189061
TI  - Administration of the peroxisomal proliferator-activated receptor gamma agonist
      pioglitazone during fractionated brain irradiation prevents radiation-induced
      cognitive impairment.
AB  - PURPOSE: We hypothesized that administration of the anti-inflammatory peroxisomal
      proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone (Pio) to
      adult male rats would inhibit radiation-induced cognitive impairment. METHODS AND
      MATERIALS: Young adult male F344 rats received one of the following: (1)
      fractionated whole brain irradiation (WBI); 40 or 45 Gy gamma-rays in 4 or 4.5
      weeks, respectively, two fractions per week and normal diet; (2) sham-irradiation
      and normal diet; (3) WBI plus Pio (120 ppm) before, during, and for 4 or 54 weeks
      postirradiation; (4) sham-irradiation plus Pio; or (5) WBI plus Pio starting 24h
      after completion of WBI. RESULTS: Administration of Pio before, during, and for 4
      or 54 weeks after WBI prevented the radiation-induced cognitive impairment.
      Administration of Pio for 54 weeks starting after completion of fractionated WBI
      substantially but not significantly reduced the radiation-induced cognitive
      impairment. CONCLUSIONS: These findings offer the promise of improving the
      quality of life and increasing the therapeutic window for brain tumor patients.

PMID- 17189062
TI  - Radiation-induced cardiovascular diseases: is the epidemiologic evidence
      compatible with the radiobiologic data?
AB  - The Life Span Study of Japanese atomic bomb survivors demonstrates that radiation
      exposure significantly increased the risk of developing ischemic heart disease,
      in particular myocardial infarction. Similarly, epidemiologic investigations in
      very large populations of patients who had received postoperative radiotherapy
      for breast cancer or for peptic ulcer demonstrate that radiation exposure of the
      heart with an average equivalent single dose of approximately 2 Gy significantly
      increased the risk of developing ischemic heart disease more than 10 years after
      irradiation. These epidemiologic findings are compatible with radiobiologic data
      on the pathogenesis of radiation-induced heart disease in experimental animals.
      The critical target structure appears to be the endothelial lining of blood
      vessels, in particular arteries, leading to early functional alterations such as
      pro-inflammatory responses and other changes, which are slowly progressive.
      Research should concentrate on the interaction of these radiation-induced
      endothelial changes with the early stages of age-related atherosclerosis to
      develop criteria for optimizing treatment plans in radiotherapy and also
      potential interventional strategies.

PMID- 17189063
TI  - Five-year outcome of intraoperative conformal permanent I-125 interstitial
      implantation for patients with clinically localized prostate cancer.
AB  - PURPOSE: To report the 5-year tumor control and toxicity outcomes for patients
      with localized prostate treated with I-125 permanent implantation using an
      intraoperative real-time conformal planning technique. METHODS AND MATERIALS:
      Between January 1998 and June 2002, 367 patients with prostate cancer were
      treated with I-125 permanent interstitial implantation using a transrectal
      ultrasound-guided approach. Real-time intraoperative treatment planning which
      incorporated inverse planning optimization was used. The median follow-up time
      was 63 months. RESULTS: The median V100 and D90 were 96% and 173 Gy,
      respectively. In 96% of cases a D90 of >140 Gy was achieved. The median urethral
      and rectal doses were 100% and 33% of the prescription doses, respectively. The 5
      year PSA relapse-free survival outcomes for favorable and intermediate risk
      patients according to the ASTRO definition were 96% and 89%, respectively. In
      these patients no dosimetric parameter was identified which influenced the
      biochemical outcome. Of 38% who developed acute Grade 2 urinary symptoms, 63% had
      resolution of their symptoms within a median time of 6 months. The incidence of
      late rectal and urinary Grade 3 or higher toxicities were 1% and 4%,
      respectively. Seven percent (n = 27) developed late rectal bleeding (Grade 2) and
      19% experienced late Grade 2 urinary symptoms. CONCLUSION: Real-time
      intraoperative planning consistently achieved optimal coverage of the prostate
      with the prescription dose with concomitant low doses delivered to the urethra
      and rectum. Biochemical control outcomes were excellent at 5 years and late
      toxicity was unusual. These data demonstrate that real-time planning methods can
      consistently and reliably deliver the intended dose distribution to achieve an
      optimal therapeutic ratio between the target and normal tissue structures.

PMID- 17189064
TI  - Proctitis after external-beam radiotherapy for prostate cancer classified by
      Vienna Rectoscopy Score and correlated with EORTC/RTOG score for late rectal
      toxicity: results of a prospective multicenter study of 166 patients.
AB  - PURPOSE: To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and
      effective tool for detecting and classifying pathologic changes in the rectal
      mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its
      findings with the European Organization for Research and Treatment of Cancer
      (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity.
      METHODS AND MATERIALS: A total of 486 patients with localized prostate cancer
      underwent external-beam RT up to 70 or 74 Gy within an Austrian-German
      prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy
      was performed before and at 12 and/or 24 months after RT. Pathologic findings
      such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and
      summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were
      documented and correlated with the corresponding VRS. RESULTS: Before RT, 99% had
      a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side
      effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by
      VRS (p < 0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using
      EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages
      were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A
      significant coherence between the VRS and EORTC/RTOG was found (p < 0.01).
      CONCLUSIONS: The VRS is a feasible and effective tool for describing and
      classifying pathologic findings in the rectal mucosa after RT within a
      multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the
      VRS was significantly more sensitive.

PMID- 17189065
TI  - Expression of vascular endothelial growth factor (VEGF) in locally invasive
      prostate cancer is prognostic for radiotherapy outcome.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is an important hypoxia
      inducible pro-angiogenic protein that has been linked with an adverse survival
      outcome after radiotherapy in other cancer types: we hypothesized that this may
      also occur in prostate cancer. A retrospective study was, therefore, carried out
      to evaluate the potential of tumor VEGF expression to predict radiotherapy
      outcome in patients with high-risk prostate cancer. METHODS AND MATERIALS: Fifty
      patients with locally advanced (T3 N0 M0) tumors of Gleason score > or =6, and
      who received radiotherapy alone as primary treatment for their disease, were
      studied. Vascular endothelial growth factor expression was assessed on
      pretreatment diagnostic tumor biopsies using a semiquantitative
      immunohistochemical scoring system. The results were analyzed in relation to
      clinicopathologic factors and patient outcome including biochemical failure and
      disease-specific mortality. RESULTS: High VEGF expression was associated with a
      poor prognosis: in univariate log rank analysis, VEGF was the only significant
      prognostic factor for disease-specific survival (p = 0.035). High VEGF expression
      also associated with increased Gleason score (p = 0.02), but not posttreatment
      biochemical failure. CONCLUSION: High tumor expression of VEGF identified
      patients at high risk of failure of treatment with radiotherapy. These patients
      might benefit from additional treatment approaches incorporating anti-angiogenic
      or hypoxia-specific agents.

PMID- 17189066
TI  - Adaptive brachytherapy treatment planning for cervical cancer using FDG-PET.
AB  - PURPOSE: A dosimetric study was conducted to compare intracavitary brachytherapy
      using both a conventional and a custom loading intended to cover a positron
      emission tomography (PET)-defined tumor volume in patients with cervix cancer.
      METHODS AND MATERIALS: Eleven patients who underwent an [(18)F]-fluoro-deoxy-D
      glucose (FDG)-PET in conjunction with their first, middle, or last brachytherapy
      treatment were included in this prospective study. A standard plan that delivers
      6.5 Gy to point A under ideal conditions was compared with an optimized plan
      designed to conform the 6.5-Gy isodose surface to the PET defined volume.
      RESULTS: A total of 31 intracavitary brachytherapy treatments in conjunction with
      an FDG-PET were performed. The percent coverage of the target isodose surface for
      the first implant with and without optimization was 73% and 68% (p = 0.21). The
      percent coverage of the target isodose surface for the mid/final implant was 83%
      and 70% (p = 0.02), respectively. The dose to point A was higher with the
      optimized plans for both the first implant (p = 0.02) and the mid/last implants
      (p = 0.008). The dose to 2 cm(3) and 5 cm(3) of both the bladder and rectum were
      not significantly different. CONCLUSIONS: FDG-PET based treatment planning
      allowed for improved dose coverage of the tumor without significantly increasing
      the dose to the bladder and rectum.

PMID- 17189067
TI  - Long-term results of breast cancer irradiation treatment with low-dose-rate
      external irradiation.
AB  - PURPOSE: The aim of this study was to assess beam therapy with low-dose-rate
      (LDR) external irradiation in a group of patients with breast cancer. METHODS AND
      MATERIALS: This trial compared, from 1986 to 1989, patients with advanced breast
      cancer treated either by conventional fractionation or low-dose-rate (LDR)
      external radiotherapy (dose-rate 15 mGy/min, 5 sessions of 9 Gy delivered on 5
      consecutive days). RESULTS: A total of 21 patients were included in the
      fractionated therapy arm. At follow-up 15 years after treatment, 7 local
      recurrences had occurred, 3 patients had died of cancer, 18 patients were alive,
      10 were without evidence of disease, and 6 had evidence of disease. A total of 22
      patients had been included in the LDR arm of the study. Of these, 11 had received
      a dose of 45 Gy; thereafter, in view of severe local reactions, the dose was
      reduced to 35 Gy. There was no local recurrence in patients who had received 45
      Gy, although there were 2 local recurrences among the 11 patients after 35 Gy.
      The sequelae were severe in patients who received 45 Gy but were comparable to
      those observed in patients treated by fractionated radiotherapy who received 35
      Gy. The higher efficacy of tumor control in patients treated by LDR irradiation
      as well as the lower tolerance of normal tissue are probably related to the lack
      of repopulation. CONCLUSION: Although the patient numbers in this study are
      limited, based on our study results we conclude that the data for LDR irradiation
      are encouraging and that further investigation is warranted.

PMID- 17189068
TI  - Intensity-modulated radiation therapy for malignancies of the nasal cavity and
      paranasal sinuses.
AB  - PURPOSE: To report the clinical outcome of patients treated with intensity
      modulated radiation therapy (IMRT) for malignancies of the nasal cavity and
      paranasal sinuses. METHODS AND MATERIALS: Between 1998 and 2004, 36 patients with
      malignancies of the sinonasal region were treated with IMRT. Thirty-two patients
      (89%) were treated in the postoperative setting after gross total resection.
      Treatment plans were designed to provide a dose of 70 Gy to 95% or more of the
      gross tumor volume (GTV) and 60 Gy to 95% or more of the clinical tumor volume
      (CTV) while sparing neighboring critical structures including the optic chiasm,
      optic nerves, eyes, and brainstem. The primary sites were: 13 ethmoid sinus, 10
      maxillary sinus, 7 nasal cavity, and 6 other. Histology was: 12 squamous cell, 7
      esthesioneuroblastoma, 5 adenoid cystic, 5 undifferentiated, 5 adenocarcinoma,
      and 2 other. Median follow-up was 51 months among surviving patients (range, 9-82
      months). RESULTS: The 2-year and 5-year estimates of local control were 62% and
      58%, respectively. One patient developed isolated distant metastasis, and none
      developed isolated regional failure. The 5-year rates of disease-free and overall
      survival were 55% and 45%, respectively. The incidence of ocular toxicity was
      minimal with no patients reporting decreased vision. Late complications included
      xerophthalmia (1 patient), lacrimal stenosis (1 patient), and cataract (1
      patient). CONCLUSION: Although IMRT for malignancies of the sinonasal region does
      not appear to lead to significant improvements in disease control, the low
      incidence of complications is encouraging.

PMID- 17189069
TI  - Prospective assessment of dosimetric/physiologic-based models for predicting
      radiation pneumonitis.
AB  - PURPOSE: Clinical and 3D dosimetric parameters are associated with symptomatic
      radiation pneumonitis rates in retrospective studies. Such parameters include:
      mean lung dose (MLD), radiation (RT) dose to perfused lung (via SPECT), and pre
      RT lung function. Based on prior publications, we defined pre-RT criteria
      hypothesized to be predictive for later development of pneumonitis. We herein
      prospectively test the predictive abilities of these dosimetric/functional
      parameters on 2 cohorts of patients from Duke and The Netherlands Cancer
      Institute (NKI). METHODS AND MATERIALS: For the Duke cohort, 55 eligible patients
      treated between 1999 and 2005 on a prospective IRB-approved study to monitor RT
      induced lung injury were analyzed. A similar group of patients treated at the NKI
      between 1996 and 2002 were identified. Patients believed to be at high and low
      risk for pneumonitis were defined based on: (1) MLD; (2) OpRP (sum of predicted
      perfusion reduction based on regional dose-response curve); and (3) pre-RT DLCO.
      All doses reflected tissue density heterogeneity. The rates of grade > or =2
      pneumonitis in the "presumed" high and low risk groups were compared using
      Fisher's exact test. RESULTS: In the Duke group, pneumonitis rates in patients
      prospectively deemed to be at "high" vs. "low" risk are 7 of 20 and 9 of 35,
      respectively; p = 0.33 one-tailed Fisher's. Similarly, comparable rates for the
      NKI group are 4 of 21 and 6 of 44, respectively, p = 0.41 one-tailed Fisher's.
      CONCLUSION: The prospective model appears unable to accurately segregate patients
      into high vs. low risk groups. However, considered retrospectively, these data
      are consistent with prior studies suggesting that dosimetric (e.g., MLD) and
      functional (e.g., PFTs or SPECT) parameters are predictive for RT-induced
      pneumonitis. Additional work is needed to better identify, and prospectively
      assess, predictors of RT-induced lung injury.

PMID- 17189070
TI  - Impact of hybrid fluorodeoxyglucose positron-emission tomography/computed
      tomography on radiotherapy planning in esophageal and non-small-cell lung cancer.
AB  - PURPOSE: The aim of this study was to investigate the impact of a hybrid
      fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT)
      scanner in radiotherapy planning for esophageal and non-small-cell lung cancer
      (NSCLC). METHODS AND MATERIALS: A total of 30 patients (16 with esophageal
      cancer, 14 with NSCLC) underwent an FDG-PET/CT for radiotherapy planning
      purposes. Noncontrast total-body spiral CT scans were obtained first, followed
      immediately by FDG-PET imaging which was automatically co-registered to the CT
      scan. A physician not involved in the patients' original treatment planning
      designed a gross tumor volume (GTV) based first on the CT dataset alone, while
      blinded to the FDG-PET dataset. Afterward, the physician designed a GTV based on
      the fused PET/CT dataset. To standardize PET GTV margin definition, background
      liver PET activity was standardized in all images. The CT-based and PET/CT-based
      GTVs were then quantitatively compared by way of an index of conformality, which
      is the ratio of the intersection of the two GTVs to their union. RESULTS: The
      mean index of conformality was 0.44 (range, 0.00-0.70) for patients with NSCLC
      and 0.46 (range, 0.13-0.80) for patients with esophageal cancer. In 10 of the 16
      (62.5%) esophageal cancer patients, and in 12 of the 14 (85.7%) NSCLC patients,
      the addition of the FDG-PET data led to the definition of a smaller GTV.
      CONCLUSION: The incorporation of a hybrid FDG-PET/CT scanner had an impact on the
      radiotherapy planning of esophageal cancer and NSCLC. In future studies, we
      recommend adoption of a conformality index for a more comprehensive comparison of
      newer treatment planning imaging modalities to conventional options.

PMID- 17189071
TI  - Using economic analysis to evaluate the potential of multimodality therapy for
      elderly patients with locally advanced pancreatic cancer.
AB  - PURPOSE: Development of new and expensive drugs with activity against pancreatic
      cancer has made economic considerations more relevant to treatment decision
      making for advanced disease. Economic modeling can be used to explore the
      potential of such novel therapies and to inform clinical trial design. METHODS
      AND MATERIALS: We developed a Markov model to evaluate the cost-effectiveness of
      radiation plus fluorouracil (RT-FU) relative to no treatment in elderly patients
      with locally advanced pancreatic cancer (LAPC) and to determine the economic
      potential of radiation plus gemcitabine (RT-GEM), a novel regimen for this
      disease. We used the SEER-Medicare database to estimate effectiveness and costs
      supplemented by data from the literature where necessary. RESULTS: Relative to no
      treatment, RT-FU was associated with a cost-effectiveness ratio (ICER) of
      $68,724/QALY in the base case analysis. Compared with RT-FU, the ICER for RT-GEM
      was below $100,000/QALY when the risk of dying with the new regimen was <85% than
      with the standard regimen. However, >1,000 subjects would be necessary to
      demonstrate this level of efficacy in a randomized trial. The ICER of RT-GEM was
      most sensitive to utility values, and, at lower efficacy levels, to costs of
      gemcitabine and treatment-related toxicity. CONCLUSIONS: In elderly patients with
      LAPC, RT-FU is a cost-effective alternative to no treatment. The novel regimen of
      RT-GEM is likely to be cost-effective at any clinically meaningful benefit, but
      quality-of-life issues, drug acquisition, and toxicity-related costs may be
      relevant, especially at lower efficacy levels.

PMID- 17189072
TI  - Phase I study of oral S-1 and concurrent radiotherapy in patients with
      unresectable locally advanced pancreatic cancer.
AB  - PURPOSE: The primary objective of this study was to determine the maximum
      tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent
      radiotherapy in patients with unresectable locally advanced pancreatic cancer.
      METHODS AND MATERIALS: Patients with histopathologically proven, unresectable,
      locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in
      1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was
      administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses
      from 60 to 80 mg/m(2)/day. RESULTS: Sixteen patients were enrolled in this study.
      Three patients received S-1 at 60 mg/m(2)/day, 3 at 70 mg/m(2)/day, and 10 at 80
      mg/m(2)/day. Though 1 patient at the final dose level (80 mg/m(2)/day)
      experienced a dose limiting toxicity (biliary infection with Grade 3
      neutropenia), the MTD was not reached in this study. The most common toxicities
      were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3%
      of the patients, respectively. CONCLUSIONS: The recommended dose of S-1 with
      concurrent radiotherapy was determined to be 80 mg/m(2)/day from Day 1 to 14 and
      22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and
      radiotherapy is well tolerated and feasible and should be further investigated.

PMID- 17189073
TI  - Effect of prophylactic hyperbaric oxygen treatment for radiation-induced brain
      injury after stereotactic radiosurgery of brain metastases.
AB  - PURPOSE: The purpose of the present study was to evaluate the prophylactic effect
      of hyperbaric oxygen (HBO) therapy for radiation-induced brain injury in patients
      with brain metastasis treated with stereotactic radiosurgery (SRS). METHODS AND
      MATERIALS: The data of 78 patients presenting with 101 brain metastases treated
      with SRS between October 1994 and September 2003 were retrospectively analyzed. A
      total of 32 patients with 47 brain metastases were treated with prophylactic HBO
      (HBO group), which included all 21 patients who underwent subsequent or prior
      radiotherapy and 11 patients with common predictors of longer survival, such as
      inactive extracranial tumors and younger age. The other 46 patients with 54 brain
      metastases did not undergo HBO (non-HBO group). The radiation-induced brain
      injuries were divided into two categories, white matter injury (WMI) and
      radiation necrosis (RN), on the basis of imaging findings. RESULTS: The radiation
      induced brain injury occurred in 5 lesions (11%) in the HBO group (2 WMIs and 3
      RNs) and in 11 (20%) in the non-HBO group (9 WMIs and 2 RNs). The WMI was less
      frequent for the HBO group than for the non-HBO group (p = 0.05), although
      multivariate analysis by logistic regression showed that WMI was not
      significantly correlated with HBO (p = 0.07). The 1-year actuarial probability of
      WMI was significantly better for the HBO group (2%) than for the non-HBO group
      (36%) (p < 0.05). CONCLUSIONS: The present study showed a potential value of
      prophylactic HBO for the radiation-induced WMIs, which justifies further
      evaluation to confirm its definite benefit.

PMID- 17189074
TI  - Radiotherapy of metastatic spinal cord compression in very elderly patients.
AB  - PURPOSE: Owing to the aging of the population, the proportion of elderly patients
      receiving cancer treatment has increased. This study investigated the results of
      radiotherapy (RT) for metastatic spinal cord compression (MSCC) in the very
      elderly, because few data are available for these patients. METHODS AND
      MATERIALS: The data from 308 patients aged > or =75 years who received short
      course (treatment time 1-5 days) or long-course RT (2-4 weeks) for MSCC were
      retrospectively analyzed for functional outcome, local control, and survival.
      Furthermore, nine potential prognostic factors were investigated: gender,
      performance status, interval from tumor diagnosis to MSCC, tumor type, number of
      involved vertebrae, other bone or visceral metastases, ambulatory status, and
      speed at which motor deficits developed. RESULTS: Improvement of motor deficits
      occurred in 25% of patients, with no further progression of MSCC in an additional
      59%. The 1-year local control and survival rate was 92% and 43%, respectively.
      Improved functional outcomes were associated with ambulatory status and slower
      developing motor deficits. Improved local control resulted from long-course RT.
      Improved survival was associated with a longer interval from tumor diagnosis to
      MSCC, tumor type (breast/prostate cancer, myeloma/lymphoma), lack of visceral or
      other bone metastases, ambulatory status, and a slower development of motor
      deficits. CONCLUSION: Short- and long-course RT are similarly effective in
      patients aged > or =75 years regarding functional outcome and survival. Long
      course RT provided better local control. Patients with better expected survival
      should receive long-course RT and others short-course RT. The criteria for
      selection of an appropriate regimen for MSCC in very elderly patients should be
      the same as for younger individuals.

PMID- 17189075
TI  - Radiosensitization of head/neck squamous cell carcinoma by adenovirus-mediated
      expression of the Nbs1 protein.
AB  - PURPOSE: Local failure and toxicity to adjacent critical structures is a
      significant problem in radiation therapy of cancers of the head and neck. We are
      developing a gene therapy based method of sensitizing head/neck squamous cell
      carcinoma (HNSCC) to radiation treatment. As patients with the rare hereditary
      disorder, Nijmegen breakage syndrome, show radiation sensitivity we hypothesized
      that tumor-specific disruption of the function of the Nbs1 protein would lead to
      enhanced cellular sensitivity to ionizing radiation. EXPERIMENTAL PROCEDURES: We
      constructed two recombinant adenoviruses by cloning the full-length Nbs1 cDNA as
      well as the C-terminal 300 amino acids of Nbs1 into an adenovirus backbone under
      the control of a CMV promoter. The resulting adenoviruses were used to infect
      HNSCC cell line JHU011. These cells were evaluated for expression of the viral
      based constructs and assayed for clonogenic survival following radiation
      exposure. RESULTS: Exposure of cells expressing Nbs1-300 to ionizing radiation
      resulted in a small reduction in survival relative to cells infected with control
      virus. Surprisingly, expression of full-length Nbs1 protein resulted in markedly
      enhanced sensitivity to ionizing radiation. Furthermore, the use of a
      fractionated radiation scheme following virus infection demonstrates that
      expression of full-length Nbs1 protein results in significant reduction in cell
      survival. CONCLUSIONS: These results provide a proof of principle that disruption
      of Nbs1 function may provide a means of enhancing the radiosensitivity of head
      and neck tumors. Additionally, this work highlights the Mre11 complex as an
      attractive target for development of radiation sensitizers.

PMID- 17189076
TI  - Enhancing the effect of radionuclide tumor targeting, using lysosomotropic weak
      bases.
AB  - PURPOSE: The aim of the present study was to investigate if treatment with
      lysosomotropic weak bases could increase the intracellular retention of
      radiohalogens and thereby increase the therapeutic effect of radionuclide tumor
      targeting. METHODS AND MATERIALS: Four different lysosomotropic bases,
      chloroquine, ammonium chloride, amantadine, and thioridazine, were investigated
      for their ability to increase radiohalogen retention in vitro. The two most
      promising substances, chloroquine and ammonium chloride, were studied in several
      cell lines (A431, U343MGaCl2:6, SKOV-3, and SKBR-3) in combination with
      radiolabeled epidermal growth factor (EGF) or the HER2 binding affibody
      (Z(HER2:4))(2). RESULTS: The uptake and retention of radionuclides was found to
      be substantially increased by simultaneous treatment with the lysosomotropic
      bases. The effect was, however, more pronounced in the epidermal growth
      factor:epidermal growth factor receptor (EGF:EGFR) system than in the
      (Z(HER2:4))(2):HER2 system. The therapeutic effect of ammonium chloride treatment
      combined with (211)At-EGF was also studied. The effect obtained after combined
      treatment was found to be much better than after (211)At-EGF treatment alone.
      CONCLUSIONS: The encouraging results from the present study indicate that the use
      of lysosomotropic weak bases is a promising approach for increasing the
      therapeutic effect of radionuclide targeting with radiohalogens.

PMID- 17189077
TI  - Image-guided in vivo dosimetry for quality assurance of IMRT treatment for
      prostate cancer.
AB  - PURPOSE: In external beam radiotherapy (EBRT) and especially in intensity
      modulated radiotherapy (IMRT), the accuracy of the dose distribution in the
      patient is of utmost importance. It was investigated whether image guided in vivo
      dosimetry in the rectum is a reliable method for online dose verification.
      METHODS AND MATERIALS: Twenty-one dose measurements were performed with an
      ionization chamber in the rectum of 7 patients undergoing IMRT for prostate
      cancer. The position of the probe was determined with cone beam computed
      tomography (CBCT). The point of measurement was determined relative to the
      isocenter and relative to an anatomic reference point. The dose deviations
      relative to the corresponding doses in the treatment plan were calculated. With
      an offline CT soft-tissue match, patient positioning after ultrasound was
      verified. RESULTS: The mean magnitude +/- standard deviation (SD) of patient
      positioning errors was 3.0 +/- 2.5 mm, 5.1 +/- 4.9 mm, and 4.3 +/- 2.4 mm in the
      left-right, anteroposterior and craniocaudal direction. The dose deviations in
      points at corresponding positions relative to the isocenter were -1.4 +/- 4.9%
      (mean +/- SD). The mean dose deviation at corresponding anatomic positions was
      6.5 +/- 21.6%. In the rare event of insufficient patient positioning, dose
      deviations could be >30% because of the close proximity of the probe and the
      posterior dose gradient. CONCLUSIONS: Image-guided dosimetry in the rectum during
      IMRT of the prostate is a feasible and reliable direct method for dose
      verification when probe position is effectively controlled.

PMID- 17189078
TI  - Tumor and normal tissue motion in the thorax during respiration: Analysis of
      volumetric and positional variations using 4D CT.
AB  - PURPOSE: To investigate temporospatial variations of tumor and normal tissue
      during respiration in lung cancer patients. METHODS AND MATERIALS: In 14
      patients, gross tumor volume (GTV) and normal tissue structures were manually
      contoured on four-dimensional computed tomography (4D-CT) scans. Structures were
      evaluated for volume changes, centroid (center of mass) motion, and phase
      dependence of variations relative to inspiration. Only volumetrically complete
      structures were used for analysis (lung in 2, heart in 8, all other structures in
      >10 patients). RESULTS: During respiration, the magnitude of contoured volumes
      varied up to 62.5% for GTVs, 25.5% for lungs, and 12.6% for hearts. The range of
      maximum three-dimensional centroid movement for individual patients was 1.3-24.0
      mm for GTV, 2.4-7.9 mm for heart, 5.2-12.0 mm for lungs, 0.3-5.5 mm for skin
      markers, 2.9-10.0 mm for trachea, and 6.6-21.7 mm for diaphragm. During
      respiration, the centroid positions of normal structures varied relative to the
      centroid position of the respective GTV by 1.5-8.1 mm for heart, 2.9-9.3 mm for
      lungs, 1.2-9.2 mm for skin markers, 0.9-7.1 mm for trachea, and 2.7-16.4 mm for
      diaphragm. CONCLUSION: Using 4D-CT, volumetric changes, positional alterations as
      well as changes in the position of contoured structures relative to the GTV were
      observed with large variations between individual patients. Although the
      interpretation of 4D-CT data has considerable uncertainty because of 4D-CT
      artifacts, observer variations, and the limited acquisition time, the findings
      might have a significant impact on treatment planning.

PMID- 17189079
TI  - Delineation of brain AVMs on MR-Angiography for the purpose of stereotactic
      radiosurgery.
AB  - PURPOSE: To assess the dosimetric consequences of brain arteriovenous
      malformation (bAVM) delineation on magnetic resonance angiography (MRA) for the
      purpose of stereotactic radiosurgery. METHODS AND MATERIALS: Three observers
      contoured a bAVM in 20 patients, using digital subtraction angiography (V(DSA))
      and three-dimensional time-of-flight MRA (V(MRA)). Displacement between contours
      was calculated. Agreement and differences between observers and imaging
      modalities were assessed. A standardized treatment plan with dynamic conformal
      arcs was generated and dosimetric coverage of all contours and the volume of
      normal brain tissue within the high dose region was determined. RESULTS: The
      generalized reliability coefficient was "fair" for target volume (0.79), but
      "poor" for displacement (0.35). V(MRA) was larger than V(DSA) (5.0 vs. 4.0 mL, p
      = 0.001). No difference in displacement was found (2.8 vs. 2.5 mm, p = 0.156).
      Dosimetric coverage of V(MRA) was 62.9% (95% CI, 56.9-68.8) when V(DSA) was used
      as planning target volume, and coverage of V(DSA) was 83.5% (95% CI, 78.1-88.8)
      when V(MRA) was used for planning (p < 0.001). The mean volume of normal brain
      within the 80% isodose was larger when the bAVM was delineated on MRA (0.7 vs.
      1.0 mL (p = 0.02) for targets < or =3 mL and 3.7 vs. 7.0 mL (p = 0.01) for
      targets >3 mL). CONCLUSIONS: Brain arteriovenous malformations delineated on MRA
      are larger and more randomly displaced. However, for bAVMs < or =3 mL, the
      difference in volume of normal brain tissue within the high-dose region does not
      seem to be clinically relevant. Therefore, MRA-images might be used as the sole
      imaging modality for the radiosurgical treatment of bAVMs < or =3 mL when the
      bAVM is located in a noneloquent position.

PMID- 17189080
TI  - In regards to Thames et al.: increasing external beam dose for T1-T2 prostate
      cancer: effect on risk groups. (Int J Radiat Oncol Biol Phys 2006;65:975-981).

PMID- 17189081
TI  - Epidermal growth factor receptor and rectal cancer: in regard to Kim et al. (Int
      J Radiat Oncol Biol Phys 2006;66:195-200).

PMID- 17189082
TI  - Renal dysfunction after total body irradiation: dose-effect relationship: in
      regard to Kal and van Kempen-Harteveld (Int J Radiat Oncol Biol Phys 2006;65:1228
      1232).

PMID- 17189085
TI  - Clinical evaluation of a new starter formula for infants containing live
      Bifidobacterium longum BL999 and prebiotics.
AB  - OBJECTIVES: The larger number of bifidobacteria in the intestine of breast-fed
      infants has been associated with their better health compared with formula-fed
      infants. We assessed the safety and tolerability of an experimental formula
      containing 2 x 10(7) colony-forming units of Bifidobacterium longum BL999 and 4
      g/L of a prebiotic mixture containing 90% galacto-oligosaccharides and 10% fructo
      oligosaccharides. METHODS: A 7-mo prospective, randomized, reference-controlled,
      double-blinded trial was performed in infants who were not breast fed after the
      14th day of birth. One hundred thirty-eight infants were enrolled and assigned to
      receive the control or experimental formula until they were 112 d old. Mean
      weight gain (primary outcome) and recumbent length, head circumference,
      tolerability (gastrointestinal symptoms), and overall morbidity (secondary
      outcomes) were measured at 14, 28, 56, 84, and 112 d of age. RESULTS: Equivalence
      in mean weight gain between the two groups was shown. The treatment difference in
      the intention-to-treat and per-protocol populations were within the predefined
      equivalence boundaries of +/-3.9 g/d. No statistically significant difference in
      recumbent length, head circumference, or incidence of adverse events was found
      between the two groups. Infants in the experimental group had fewer incidences of
      constipation and had stool characteristics that suggest that the experimental
      formula was tolerated well. Furthermore, these infants showed a trend toward
      fewer respiratory tract infections. CONCLUSIONS: The starter formula containing
      BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well
      tolerated.

PMID- 17189086
TI  - Early transpyloric enteral nutrition in critically ill children.
AB  - OBJECTIVE: We compared the tolerance of early (within the first 24 h after
      admission to the pediatric intensive care unit) and late transpyloric enteral
      nutrition in critically ill children. METHODS: We performed a prospective
      observational study including all critically ill children fed using transpyloric
      enteral nutrition. The clinical characteristics, energy intake, tolerance, and
      complications of nutritional delivery between the children with early (first 24
      h) and late (after 24 h, range 1-43 d) transpyloric enteral nutrition were
      compared. RESULTS: Transpyloric nutrition was started within the first 24 h in
      202 (38.5%) of the 526 children. There were no differences in the diagnoses,
      incidence of organ disturbances, doses of vasoactive drugs, or mortality between
      the two groups. There were no differences in the maximum number of calories
      delivered or in the duration of the nutrition between children with early and
      late transpyloric nutrition. The incidence of abdominal distention was lower in
      the children receiving early transpyloric nutrition (3.5%) than in those
      receiving nutrition at a later date (7.8%; P < 0.05). Moreover, 6.3% of patients
      presented diarrhea, with no difference being found between the two groups.
      CONCLUSION: Early transpyloric enteral nutrition is well tolerated in critically
      ill children and is not associated with an increase in incidence of
      complications.

PMID- 17189087
TI  - Effect of cereal-thickened formula and upright positioning on regurgitation,
      gastric emptying, and weight gain in infants with regurgitation.
AB  - OBJECTIVE: We compared the effect of cereal-thickened formula or postural therapy
      on regurgitation and gastroesophageal reflux, weight gain, and gastric emptying
      in infants. METHODS: We performed a prospective trial in exclusively formula-fed
      infants 2 to 6 mo of age presenting with regurgitation or vomiting at least three
      times a day. Infants were randomized into two groups; group A received cereal
      thickened formula versus group B who were placed in a postprandial upright
      position for 90 min and evaluated over an 8-wk period. A 90-min technetium 99m
      milk scintigraphy was performed before and at the end of the intervention period.
      RESULTS: Thirty-one infants were included in group A and 32 in group B; at
      inclusion, there were no anthropometric differences between groups (P = 0.813
      0.955). After 4 and 8 wk, the difference in regurgitation frequency per day
      between groups A and B had become significant (at 4 wk, 2.39 +/- 0.86 for group A
      versus 2.84 +/- 0.81 for group B, P = 0.039; at 8 wk, 1.61 +/- 0.76 for group A
      versus 2.38 +/- 0.83 for group B, P < 0.001). The volume ingested per meal was
      not different between groups after 4 wk, although this parameter showed a larger
      intake in group A after 8 wk (156.8 +/- 23.5 mL for group A versus 143.4 +/- 25.1
      mL for group B, P = 0.035), resulting in a significant difference in mean caloric
      intake. Gastric emptying after 8 wk showed no significant difference between
      groups A and B. Group A infants had significantly greater weight gain than did
      group B infants after 4 wk (636.2 +/- 103.4 g for group A versus 577.4 +/- 102.7
      g for group B, P = 0.03) and 8 wk (1261.3 +/- 131.4 g for group A versus 1121.4
      +/- 137.2 g for group B, P < 0.001). After 8 wk of intervention, the increase in
      length was significantly greater in group A than in group B (5.2 +/- 0.6 cm for
      group A versus 4.7 +/- 0.6 cm for group B, P = 0.032). CONCLUSION: Cereal
      thickened formula is significantly more efficacious than postural therapy in
      decreasing the frequency of regurgitation in regurgitating infants. Treatment of
      regurgitation with cereal-thickened formula results in an increased caloric
      intake ( approximately 25%), related to increased gain in weight and length, in
      comparison with regular formula and positioning therapy.

PMID- 17189088
TI  - Effect of severe undernutrition and subsequent refeeding on gut mucosal protein
      fractional synthesis in human subjects.
AB  - OBJECTIVE: Undernutrition has been associated with gut mucosal atrophy, impaired
      absorption, and increased permeability. This study investigated the effect of
      severe undernutrition and subsequent refeeding on gastric and duodenal mucosal
      protein fractional syntheses (MPFS). METHODS: MPFS was investigated in the
      gastric body, antrum, and duodenum of 23 severely undernourished patients by
      means of (14)C-leucine incorporation into tissue protein and repeated after a
      period of refeeding. Results were evaluated in comparison with a group of 22
      healthy controls and presented as mean +/- standard error of the mean. RESULTS:
      The mean body index of the undernourished patients was 13.29 +/- 0.33 kg/m(2)
      versus 22.67 +/- 0.63 kg/m(2) in the controls (P < 0.001). MPFS in the controls
      and undernourished patients were similar (gastric body, 36.49 +/- 2.88 versus
      33.41 +/- 3.08%/d; gastric antrum, 25.51 +/- 2.20 versus 24.95 +/- 2.32%/d;
      duodenum, 25.90 +/- 2.58 versus 25.49 +/- 1.99%/d). After refeeding, the body
      mass index of the undernourished patients increased to 15.87 +/- 0.44 kg/m(2) (P
      < 0.001). The MPFS increased significantly (gastric body, 51.80 +/- 8.12%/d, P <
      0.05; gastric antrum, 33.44 +/- 3.66%/d, P < 0.05; duodenum, 46.27 +/- 8.02%/d, P
      < 0.01), with the MPFS of the duodenum significantly greater than the control
      values (P = 0.01). CONCLUSION: Despite severe undernutrition, MPFS of the gastric
      body, antrum, and duodenum remained similar to control values. Enteral feeding
      resulted in a significant increase in MPFS, indicating a trophic response.

PMID- 17189089
TI  - Predictors of the metabolic syndrome and correlation with computed axial
      tomography.
AB  - OBJECTIVE: We investigated which anthropometric variables or imaging techniques,
      dual-energy x-ray absorptiometric densitometry (DXA) or bioelectric impedance
      analysis (BIA), are the most important determinants of the metabolic syndrome. We
      also evaluated the correlation between anthropometric parameters and DXA and
      computed axial tomography (CAT) in predicting visceral fat. METHODS: In a series
      of 399 overweight or obese patients (29.8% male and 70.2% female), anthropometric
      variables and imaging techniques (DXA or BIA) were measured and correlated with
      each component of the metabolic syndrome (diagnosed according to the criteria of
      the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of
      High Blood Cholesterol in Adults of the National Cholesterol Education Program
      [Adult Treatment Panel III], with the exception of waist circumference). In a
      subpopulation of 109 patients, CAT was used to assess visceral fat and its
      correlation with the anthropometric variables and DXA. RESULTS: Applying receiver
      operating characteristic curves, the waist/height ratio was the best determinant
      of the metabolic syndrome (0.758, 95% confidence interval 0.634-0.882). The intra
      abdominal diameter determined by DXA (r = 0.657, P < 0.001) and the waist/hip
      ratio (r = 0.603, P < 0.001) had the best correlation with visceral fat as
      measured by CAT. CONCLUSION: The prediction of visceral fat in overweight and
      obese patients, as assessed by anthropometric tests and DXA, offers a good
      alternative to CAT, without significant differences between them.

PMID- 17189090
TI  - Kurozu moromimatsu inhibits tumor growth of Lovo cells in a mouse model in vivo.
AB  - OBJECTIVE: In Japan, rice vinegar that has been matured and fermented for years
      in earthenware jars is considered a health food with anticolon cancer action. It
      is divided into the liquid component (Kurozu) and the sediment (Kurozu
      moromimatsu), which contains large amounts of organic materials and minerals. The
      effect of Kurozu moromimatsu (Kurozu-M) on cancer has not yet been examined. In
      this study, we examined the activity of Kurozu-M on colon cancer and investigated
      the mechanisms involved, focusing on active oxygen generation, apoptosis, and
      metalloproteinases (MMPs). METHODS: We used Lovo cells transplanted into nude
      mice as an experimental model. We measured the tumor volume and MMP levels and
      conducted hematoxylin-eosin staining (for polymorphonuclear leukocytes), terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining (for
      apoptosis), and immunostaining for nitrotyrosine (a marker of active oxygen
      generation) in control, Kurozu-treated, and Kurozu-M--treated groups. RESULTS:
      The tumor volume was the same in the control group (231 +/- 36 mm(3)) and Kurozu
      group (238 +/- 52 mm(3)), but was significantly reduced in the Kurozu-M group
      (152 +/- 28 mm(3), P < 0.001 versus control). Apoptosis of tumor cells and
      accumulation of polymorphonuclear leukocytes were not observed. Nitrotyrosine
      production, total MMP levels, and MMP activation were significantly reduced in
      the Kurozu-M group. CONCLUSION: The administration of Kurozu-M prolonged the
      lifespan of cancer cell-transplanted mice, inhibited tumor progression, and
      reduced nitrotyrosine production and MMP activation, but did not induce
      apoptosis.

PMID- 17189091
TI  - Antimicrobial susceptibilities and distribution of resistance genes for beta
      lactams and macrolides in Streptococcus pneumoniae isolated between 2002 and 2004
      in Tokyo.
AB  - Antimicrobial susceptibilities of 205 Streptococcus pneumoniae strains isolated
      between 2002 and 2004 in Japan were examined and the distribution of genes for
      resistance to penicillins and macrolides were investigated by polymerase chain
      reaction. The molecular epidemiology of 92 randomly selected isolates was also
      examined by pulsed-field gel electrophoresis (PFGE). The numbers of S. pneumoniae
      isolates resistant to benzylpenicillin, clarithromycin and tetracycline were,
      respectively, 39 (19%), 111 (54%) and 155 (76%), and the numbers increased
      annually. All isolates were susceptible to amoxicillin, fluoroquinolones,
      vancomycin and linezolid. Analysis of mutations in the genes for penicillin
      binding protein showed that 92% of isolates had mutations in pbp1a, pbp2b and/or
      pbp2x. Susceptibility to benzylpenicillin decreased with increasing number of
      mutated pbp genes. The macrolide resistance genes ermB and mefA were found in 99
      (48%) and 76 (37%) isolates, respectively. The presence of ermB was associated
      with high-level resistance to macrolides, and the percentage of isolates with
      ermB increased annually. The presence of mefA also increased with increasing
      number of mutated pbp genes. Although the 92 isolates belonged to 74 PFGE types,
      three groups with an 80% similarity in their PFGE patterns were found at high
      frequency. Two of the three groups contained no isolates susceptible to
      penicillin and/or tetracycline, and their percentages increased annually. Our
      results suggest that the number of S. pneumoniae isolates with reduced
      susceptibility due to accumulation of resistance genes has been increasing.

PMID- 17189093
TI  - Human serum activity of telithromycin, azithromycin and amoxicillin/clavulanate
      against common aerobic and anaerobic respiratory pathogens.
AB  - Telithromycin is a new ketolide antimicrobial with a good in vitro activity
      against both aerobic and anaerobic respiratory pathogens. In this study, we
      evaluated the antibacterial activity over time of telithromycin (800mg),
      azithromycin (500mg), and amoxicillin/clavulanate (875/125mg) in serum following
      single oral doses of these agents to 10 healthy subjects. Inhibitory and
      bactericidal titers were determined at 2, 6, 12, and 24h after each dose and the
      median titer was used to determine antibacterial activity. Against two
      azithromycin-resistant strains of Streptococcus pneumoniae, both telithromycin
      (MIC=0.25 and 0.5 microg/mL) and amoxicillin/clavulanate exhibited inhibitory and
      cidal activity for at least 6h. All three antibiotics provided prolonged
      (>or=12h) inhibitory activity against strains of Hemophilus influenzae
      (telithromycin MIC=4.0 microg/ml). Both telithromycin and amoxicillin/clavulanate
      exhibited rapid and prolonged inhibitory activity (>or=12h) against each of the
      anaerobes studied (Finegoldia [Peptostreptococcus] magna Peptostreptococcus
      micros, Prevotella bivia, and Prevotella melaninogenica). Moreover, both agents
      provided bactericidal activity against both Prevotella species. In this ex vivo
      pharmacodynamic study, we found that telithromycin provided rapid and prolonged
      antibacterial activity in serum against macrolide-resistant strains of S.
      pneumoniae, beta-lactamase-positive and -negative strains of H. influenzae, and
      common respiratory anaerobic pathogens. These findings suggest that telithromycin
      could have clinical utility in the treatment of community-acquired mixed aerobic
      anaerobic respiratory tract infections, including chronic sinusitis and
      aspiration pneumonia.

PMID- 17189092
TI  - Differences in the changes in resistance patterns to third- and fourth-generation
      cephalosporins and piperacillin/tazobactam among Klebsiella pneumoniae and
      Escherichia coli clinical isolates following a restriction policy in a Greek
      tertiary care hospital.
AB  - The aim of the present study was to investigate whether replacement of broad
      spectrum cephalosporins (CEPs) by piperacillin/tazobactam (TZP) as first-line
      empirical therapy may have an effect on beta-lactam resistance among Klebsiella
      pneumoniae and Escherichia coli in a tertiary care hospital. Data regarding CEP
      and TZP consumption and resistance were collected on a bimonthly basis during an
      open-label 2-year (1 year observational and 1 year interventional) study.
      Consumption of ceftazidime was reduced by 64.5%. In contrast, consumption of the
      other third-generation CEPs (cefotaxime and ceftriaxone) remained almost stable,
      whereas an increase in consumption of TZP by 2.8-fold was observed. A significant
      decrease in resistance to third-generation cephalosporins among K. pneumoniae
      isolates was observed, and the incidence of extended-spectrum beta-lactamase
      producing isolates was notably reduced. These findings were less evident among E.
      coli isolates. Despite the significant increase in TZP consumption, the
      respective resistance rates of both bacterial species examined have remained
      almost unchanged.

PMID- 17189095
TI  - Colistin offers prolonged survival in experimental infection by multidrug
      resistant Acinetobacter baumannii: the significance of co-administration of
      rifampicin.
AB  - The effect of colistin on bacterial eradication and survival was tested in
      experimental infection by multidrug-resistant Acinetobacter baumannii. The thigh
      infection model was applied in 86 neutropenic Wistar rats. Six rats were used for
      the induction of neutropenia and for the selection of the dose regimen of
      colistin; the remainder was equally divided into four groups: A, controls; B,
      rifampicin; C, colistin; and D, both agents. Therapy was administered 5 h after
      bacterial challenge; 5mg/kg of rifampicin was administered intravenously and
      3mg/kg of colistin intramuscularly. Survival was recorded in 10 animals of each
      group. The remaining 10 rats per group were killed 4h after therapy; blood and
      tissue samples were sampled. Median survival of animals of groups A, B, C and D
      was 2.00, 2.50, 4.00 and 4.00 days, respectively (P=0.0048 between A and C and
      P=0.0012 between A and D. Mortality rates after 6 days of follow-up were 100,
      100, 100 and 70%, respectively (P=0.018 between groups). Statistically
      significant decreases of bacteria were found in blood, liver, lung and spleen of
      group B compared with A; in lung of group C compared with A; and in blood and
      liver of group D compared with A. Colistin was effective in prolonging survival
      in an experimental thigh infection by multidrug-resistant A. baumannii in
      neutropenic rats. Its activity was enhanced after co-administration with
      rifampicin. These results mandate the application of colistin in the event of
      infections by multidrug-resistant pathogens and the need for its co
      administration with rifampicin.

PMID- 17189094
TI  - A pilot study testing whether concentrations of levofloxacin in interstitial
      space fluid of soft tissues may serve as a surrogate for predicting its
      pharmacokinetics in lung.
AB  - Recent observations indicate that pharmacokinetics of beta-lactam antibiotics in
      the lung can be predicted by the use of concentration versus time profiles in
      peripheral soft tissues. If this observation is transferred to other classes of
      antimicrobials, measurement of antimicrobial concentrations in peripheral tissues
      would enable prediction of the pharmacokinetics of antimicrobials at the site of
      the respiratory tract infection. We set out to test the hypothesis that
      concentrations of the fluoroquinolone levofloxacin in the respiratory tract can
      be predicted on the basis of knowledge of its pharmacokinetics in peripheral soft
      tissues. After administration of a single intravenous dose of 500mg of
      levofloxacin, microdialysis was used to describe the concentration versus time
      profiles of levofloxacin in the interstitial space fluid of lung tissue of
      patients (n=5) undergoing elective lung surgery. These data were compared with
      the concentration versus time courses in the interstitial space fluid of skeletal
      muscle and subcutaneous adipose tissue of healthy volunteers (n=7). The median
      AUC(0-infinity) of free levofloxacin in lung (2267mg x min/L, 1980-2355) was
      about 2-fold and 1.5-fold lower compared with skeletal muscle (4381mg x min/L,
      range 1720-8195) and adipose tissue (3492mg x min/L, range 1323-6420) of healthy
      controls, respectively. Concentrations in the interstitial space fluid of the
      lung were descriptively lower compared with corresponding concentrations in
      peripheral soft tissues. This is in contrast to previous observations made for
      the class of beta-lactam antibiotics, and indicates that pharmacokinetics of
      levofloxacin derived from soft tissues may not be used uncritically for
      prediction of levofloxacin concentrations in the interstitium of the lung.

PMID- 17189096
TI  - Efficacy and safety of 3-day azithromycin versus 5-day moxifloxacin for the
      treatment of acute bacterial exacerbations of chronic bronchitis.
AB  - Antibiotic therapy is of clinical benefit in certain patients with acute
      exacerbations of chronic bronchitis (AECB). In this randomised, investigator
      blinded, multicentre trial, azithromycin (500mg once a day (qd) for 3 days) was
      compared with moxifloxacin (400mg qd for 5 days) for the treatment of outpatients
      with AECB (forced expiratory volume in 1s (FEV(1)) >35%). Of 342 patients
      randomised to either treatment, 169 received azithromycin and 173 received
      moxifloxacin. The mean age in the azithromycin and moxifloxacin groups was 56.4
      years and 55.5 years, respectively. In the intent-to-treat analysis, clinical
      success rates for azithromycin and moxifloxacin were comparable at Days 10-12
      (90% versus 90%, respectively) and Days 22-26 (81% versus 82%, respectively).
      Among patients who were culture-positive at baseline for Streptococcus
      pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Haemophilus
      parainfluenzae, clinical efficacy for azithromycin versus moxifloxacin at Days 10
      12 was 93% versus 84%, respectively, and at Days 22-26 it was 89% versus 73%,
      respectively. The incidence of at least one treatment-related adverse event (AE)
      in the azithromycin and moxifloxacin groups was 18.3% and 19.1%, respectively.
      The most common AEs were diarrhoea, nausea, abdominal pain and vaginitis. Most
      treatment-related AEs were of mild or moderate severity, with no serious
      treatment-related AEs. One subject in the moxifloxacin group discontinued
      treatment owing to a treatment-related AE (precordial pain and dry throat).
      Compliance with both regimens was >90%. Three-day azithromycin and 5-day
      moxifloxacin demonstrate comparable efficacy and safety for the treatment of AECB
      in outpatients.

PMID- 17189097
TI  - Fosfomycin in the treatment of extended spectrum beta-lactamase-producing
      Escherichia coli-related lower urinary tract infections.
AB  - Fosfomycin tromethamine (FT) is effective in vitro in extended spectrum beta
      lactamase (ESBL)-producing Escherichia coli strains. The aim of this study was to
      evaluate the effect of FT in the treatment of ESBL-producing E. coli-related
      lower urinary tract infection. All patients were aged >18; had dysuria or
      problems with frequency or urgency in passing urine; had >20leukocytes/mm(3) in
      urine sediment and an ESBL-producing E. coli urine culture (>10(5)cfu/mm(3)); no
      leukocytosis or fever; and were treated with FT between September 2004 and July
      2006 in our outpatient clinic and hospital. ESBL detection was performed by
      double disk synergy tests. All patients had received FT (3gx1 every other night,
      three times) and had a control urine culture taken 7 to 9 days after this
      therapy. Clinical success was defined as resolution of symptoms on the control
      visit; microbiological success was defined as a sterile control urine culture. In
      all, 52 patients (aged 55.0+/-18.3, range 19-85; 25 males, 27 females) were
      included in the study. Overall clinical and microbiological success was 94.3%
      (49/52) and 78.5% (41/52), respectively. Although it is not a randomized
      controlled study, these data show that FT may be a suitable, effective and cheap
      alternative in the treatment of ESBL-producing E. coli-related lower urinary
      tract infection.

PMID- 17189098
TI  - The prophylactic effectiveness of various antifungal agents against the
      progression of trichosporonosis fungemia to disseminated disease in a neutropenic
      mouse model.
AB  - Neutropenic mice with latent trichosporonemia were given various antifungal
      agents (amphotericin B, fluconazole, itraconazole) or saline to determine which
      antifungal agent could be useful for prophylaxis. The 3-week-survival rate was
      80% in the fluconazole group, 50% in the amphotericin B group, 45% in the
      itraconazole group, and 30% in the saline group. Compared with the other
      antifungal agents, fluconazole offered superior prophylaxis against the
      progression of trichosporonosis fungemia to disseminated disease (P<0.05). These
      results suggest that clinical studies are warranted to investigate fluconazole
      prophylaxis of trichosporonosis progression in neutropenic patients, such as
      people receiving chemotherapy and patients who have received solid organ
      transplants.

PMID- 17189099
TI  - Analysis of plasmids encoding extended-spectrum beta-lactamases (ESBLs) from
      Escherichia coli isolated from non-hospitalised patients in Seville.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging
      pathogen in the community. We investigated the specific types of ESBLs in E. coli
      isolates from non-hospitalised patients and the plasmids harbouring these ESBLs.
      Forty-eight consecutive ESBL-producing E. coli were studied. All the isolates
      were clonally unrelated. ESBLs were characterised by sequencing. Mobility of the
      undigested plasmids was investigated both by conventional electrophoresis and by
      pulsed-field gel electrophoresis. Southern restriction fragment length
      polymorphism (RFLP) experiments were carried out by digesting plasmids with EcoRI
      and HindIII. CTX-M-14 was the most frequent ESBL (28 isolates), followed by SHV
      12 (16 isolates). Plasmids encoding CTX-M-14 appeared homogeneous both in
      hybridisation profile and mobility. In contrast, plasmids expressing SHV-12 were
      more varied in size and hybridisation patterns. Our data suggest that a single
      type or very closely related plasmids harbouring CTX-M-14 are spreading in the
      community among unrelated E. coli isolates in our area.

PMID- 17189100
TI  - Investigations into the in vitro antimicrobial activity and mode of action of the
      phenazine antibiotic D-alanylgriseoluteic acid.
AB  - D-Alanylgriseoluteic acid (AGA) is a potent antimicrobial phenazine compound
      produced by Pantoea agglomerans (Erwinia herbicola) Eh1087. Susceptibility tests
      against a range of microbes indicated that AGA had a broad spectrum of
      antimicrobial activity and was particularly active against Gram-positive
      pathogens. Comparison of the in vitro efficacy of AGA with eight other
      antibiotics against 119 clinical isolates of Streptococcus pneumoniae
      demonstrated that all were inhibited by low concentrations of AGA (minimal
      inhibitory concentration range <or=0.06-0.75 microg/mL), regardless of their
      susceptibility to other antimicrobials. Investigations into the mode of action of
      AGA revealed that it induced the SOS response in Escherichia coli and slightly
      increased the frequency of GC-AT transition mutations. In cell-free assays, both
      AGA and griseoluteic acid reduced cytochrome c in the presence of a redox
      recycler (ferredoxin-NADP(+) reductase), but AGA was six to seven times more
      readily reduced than griseoluteic acid in the absence of the reductase. The
      potency and broad spectrum of AGA activity suggest that AGA may warrant further
      investigation.

PMID- 17189101
TI  - Susceptibility of environmental versus clinical strains of pathogenic
      Aspergillus.
AB  - The objective of this study was to compare the antifungal susceptibility profiles
      of 307 environmental strains and 139 clinical isolates of Aspergillus belonging
      to six different species. Clinical and environmental strains with minimal
      inhibitory concentrations (MICs) or minimal effective concentrations
      >or=4microg/mL to amphotericin B (AMB), itraconazole (ITC), voriconazole and
      caspofungin were seldom detected. However, the susceptibility profile of
      environmental Aspergillus non-fumigatus strains suggests a native reduced
      susceptibility of Aspergillus flavus and Aspergillus terreus to AMB. A single
      environmental strain of Aspergillus nidulans showed high in vitro resistance
      (MIC>or=16 microg/mL) to ITC. Aspergillus niger showed significantly higher MIC
      values to ITC compared with the other Aspergillus spp. Conversely, A. fumigatus
      and Aspergillus glaucus showed higher susceptible profiles to the antifungals.
      Definition of the breakpoints for the antifungal agents remains urgent. The
      relationship between the susceptibility pattern and the pathogenic potential also
      deserves more attention, particularly with regard to non-fumigatus species.

PMID- 17189106
TI  - Outcomes and recurrence of initially resectable hepatocellular carcinoma meeting
      milan criteria: Rationale for partial hepatectomy as first strategy.
AB  - BACKGROUND: Partial hepatectomy and liver transplantation are considered curative
      treatments for small hepatocellular carcinoma (HCC) meeting the Milan criteria
      (solitary tumor <5 cm or up to 3 nodules <3 cm). This study was designed to
      clarify whether partial hepatectomy can be the first option in patients eligible
      for both treatments. STUDY DESIGN: All patients (n = 152) underwent curative
      surgical operation for primary HCC during 2000 to 2005 at our hospital. Eighty
      seven patients met Milan criteria and the remaining 65 did not. Outcomes were
      examined according to Milan criteria. RESULTS: After partial hepatectomy, 3-year
      survival rate was 89.6% for the group that met Milan criteria, compared with
      60.8% for the group that did not (p = 0.0044). Among patients with HCC who
      initially met the criteria, tumor recurrences were observed in 30 patients; 23
      patients met criteria and 7 patients exceeded the criteria at first diagnosis of
      recurrence. Patients with recurrence within the criteria showed a higher 3-year
      survival rate compared with patients with recurrence exceeding the criteria (100%
      versus 19.8%; p < 0.0001). Analysis of clinicopathologic variables to predict
      mode of recurrence revealed tumor size (p < 0.0001) and lower histologic
      differentiation (p = 0.0326) as positive factors for recurrence exceeding Milan
      criteria. CONCLUSIONS: Our results suggest that it is an appropriate strategy to
      treat HCC patients who meet Milan criteria with partial hepatectomy. It should be
      noted that approximately one-tenth of patients who initially met Milan criteria
      experienced postoperative recurrence that exceeded the criteria.

PMID- 17189107
TI  - Does patient satisfaction with breast reconstruction change over time? Two-year
      results of the Michigan Breast Reconstruction Outcomes Study.
AB  - BACKGROUND: Previously, we found patient satisfaction with breast reconstruction
      at postoperative year 1 significantly higher in the autogenous tissue compared
      with the expander/implant population. But breast reconstructive procedures have
      different "aging" processes, and the point at which outcomes stabilize is
      unclear. So we evaluated patient satisfaction with breast reconstruction at
      postoperative year 2 and compared the results with those from our previous study.
      STUDY DESIGN: As part of the Michigan Breast Reconstruction Outcomes Study, women
      undergoing mastectomy reconstruction (including expander/implants and pedicle and
      free transverse rectus abdominis musculocutaneous flaps [TRAM]) were
      prospectively evaluated. Preoperatively and at postoperative years 1 and 2, women
      completed a questionnaire that collected a variety of validated health status
      information. The postoperative questionnaire had an additional seven items
      assessing both general and esthetic satisfaction as separate subscales. To assess
      the effects of procedure on satisfaction and control for possible confounding,
      multiple logistic regression was used. RESULTS: At year 2, patients with TRAM
      flaps (both free and pedicle) continued to have higher levels of esthetic
      satisfaction compared with expander/implant patients (odds ratio 2.8, p < 0.01).
      But no significant differences were appreciated in esthetic satisfaction between
      women with free and pedicle TRAM flaps. In regard to general satisfaction, the
      type of reconstruction (expander/implant, pedicle TRAM, and free TRAM) had no
      statistically significant effect. CONCLUSIONS: At postoperative year 2,
      procedural differences initially found in women's general satisfaction with
      breast reconstruction diminish. Specifically, women with pedicle TRAM flaps, free
      TRAM flaps, and expander/implants had similar levels of general satisfaction. But
      at year 2, patients continue to be more esthetically satisfied with autogenous
      tissue than with expander/implant reconstructions.

PMID- 17189108
TI  - Incidence, risk factors, and complications of cholelithiasis in patients with
      home parenteral nutrition.
AB  - BACKGROUND: Previous studies showed high prevalence rates of cholelithiasis in
      patients with home parenteral nutrition (HPN). Our aim was to determine, in an
      HPN population, the incidence and risk factors for gallstones and sludge and
      their complications. STUDY DESIGN: Retrospective chart review was conducted in a
      tertiary care center. One hundred fifty-three consecutive patients who received
      HPN for longer than 2 months (range 2 to 204 months; median 15 months) between
      1985 and 1997 were followed with ultrasonography. Kaplan-Meier curves and log
      rank tests were calculated to assess risk factors for gallbladder lithiasis and
      complications. RESULTS: Thirty-four patients (22%) underwent cholecystectomy
      before HPN. Of the 119 remaining patients with gallbladder in situ,
      cholelithiasis appeared during HPN in 45 (38%). The probability of cholelithiasis
      developing during HPN was estimated to be 6.2%, 21.2%, and 38.7% at 6, 12, and 24
      months, respectively. Biliary complications developed in eight patients (7%)
      during followup. Therapy consisted of endoscopic sphincterotomy (three patients)
      or operation (five patients) with uncomplicated outcomes except for one patient;
      no death was observed. Incidence rates of biliary complication during HPN were
      estimated to be 0.0%, 4.7%, and 10.1% at 6, 12, and 24 months, respectively. Nil
      or negligible ingesta was the only factor notably associated with incidence of
      cholelithiasis (p < 0.01) or biliary complications (p < 0.01). CONCLUSIONS: This
      first incidence study shows a high rate of cholelithiasis and a low rate of
      complications during HPN. Both events were notably related to nil or negligible
      ingesta.

PMID- 17189109
TI  - Remnant liver volume to body weight ratio > or =0.5%: A new cut-off to estimate
      postoperative risks after extended resection in noncirrhotic liver.
AB  - BACKGROUND: Before extended hepatectomy of five or more segments, the remnant
      liver volume (RLV) is usually calculated as a ratio of RLV to total liver volume
      (RLV-TLV) and must be >20% to 25%. This method can lead to compare parts of
      normal liver parenchyma to others compromised by biliary or vascular obstruction
      or by portal vein embolization. Extrapolating from living-donor liver
      transplantation, we hypothesized that RLV to body weight ratio (RLV-BWR) could
      accurately assess the functional limit of hepatectomy. STUDY DESIGN: From
      September 2000 to December 2004, volumetric measurements of RLV using computed
      tomography were obtained before right-extended hepatectomy in 31 patients. RLV
      BWR of 0.5% as a critical point for patient course was compared with
      stratification by RLV-TLV (< or =25% or >25% and < or =20% or >20%). RESULTS:
      Three-month morbidity and mortality were not significantly different between
      groups RLV-TLV < or = and >25% and between groups RLV-TLV < or = and >20%, but
      increased significantly in group RLV-BWR < or = 0.5% compared with group RLV-BWR
      > 0.5% (p = 0.038 and p = 0.019, respectively) with an non-significant increase
      in death from liver failure (p = 0.077). CONCLUSIONS: RLV-BWR was more specific
      than RLV-TLV in predicting postoperative course after extended hepatectomy.
      Patients with an anticipated RLV < or = 0.5% of body weight are at considerable
      risk for hepatic dysfunction and postoperative mortality.

PMID- 17189110
TI  - Appendicitis in children treated by pediatric versus general surgeons.
AB  - BACKGROUND: Pediatric appendicitis is treated by both pediatric and general
      surgeons. We investigated whether specialty-dependent differences existed in
      patients' characteristics and outcomes. STUDY DESIGN: A retrospective chart
      review of 465 consecutive children treated for appendicitis at a university
      affiliated children's hospital during a 28-month period was performed.
      Characteristics and outcomes of patients treated by pediatric surgeons were
      compared with those treated by general surgeons. Rates of misdiagnosis,
      postoperative readmission, wound infection, intraabdominal infection, and
      duration of hospital stay were considered primary outcomes and analyzed by chi
      square, Fisher's exact test, or Student's t-test where appropriate. Hospital
      charges were considered secondary outcomes and analyzed by Wilcoxon rank sum
      test. RESULTS: Three hundred four children (65%) were treated by pediatric
      surgeons and 161 (35%) by general surgeons. Pediatric-surgeon patients were
      younger (8.3 +/- 3.6 versus 13.2 +/- 3.1 years, p < 0.001), and more likely to
      have gangrenous or perforated appendicitis (54% versus 33%, p < 0.001). There was
      no significant difference in the normal appendix rate (pediatric surgeon, 4.3%
      versus general surgeon, 5.6%, p = 0.53). In patients with simple and complicated
      appendicitis, there were no significant differences between pediatric and general
      surgeons in readmissions, postoperative complications, or hospital stay. Median
      hospital charges were not significantly different for complicated appendicitis,
      but were lower for pediatric-surgeon patients with simple appendicitis (10,735
      dollars versus 11,613 dollars, p = 0.005). CONCLUSIONS: Pediatric surgeons treat
      younger children with more severe appendicitis. There are no specialty-dependent
      differences in clinical outcomes for simple or complicated appendicitis. Hospital
      charges are lower for simple appendicitis treated by pediatric surgeons.

PMID- 17189111
TI  - Anterior anal sphincter repair for fecal incontinence: Good longterm results are
      possible.
AB  - BACKGROUND: Anterior anal sphincter repair (ASR) is standard treatment for fecal
      incontinence resulting from an obstetrically damaged anal sphincter. Longterm
      results of repair have generally been shown to be poor. This review of single
      unit series aimed to determine longterm outcomes of primary ASR for patients with
      fecal incontinence from obstetrically damaged anal sphincter. STUDY DESIGN: This
      study included patients undergoing ASR from 1995 to 1999. We perform standard
      overlapping ASR, but external and internal sphincters are repaired separately.
      The internal sphincter is sutured by direct method and only if damaged. Telephone
      interview was conducted with all patients, after which questionnaires, including
      SF-36 survey, Fecal Incontinence Quality of Life Scale questions, and Wexner
      score-type questions, were sent at median followup of 7 years. Demographic data,
      anorectal physiology, and data on short-term followup (median 12 months) were
      prospectively collected. RESULTS: Sixty-four of 72 patients returned
      questionnaires and the operation was considered a success in 80% of patients at
      median followup of 84 months. Six patients underwent additional procedures for
      incontinence and 58 patients were analyzed. Fourteen patients reported complete
      continence to stool and flatus (20%). Continence had improved from median Wexner
      score of 14 to 7 (p < 0.001). Ninety-five percent of patients were satisfied with
      their operation. There was substantial improvement in all aspects of Fecal
      Incontinence Quality of Life Scale questionnaire and SF-36. None of the anorectal
      physiology variables were of value in predicting outcomes. CONCLUSIONS: We have
      shown that good longterm results can be achieved with anterior anal sphincter
      repair. The independent muscle repair technique could explain the improved
      outcomes.

PMID- 17189112
TI  - Diagnosis and contemporary management of anastomotic leaks after gastric bypass
      for obesity.
AB  - BACKGROUND: Anastomotic leaks are a dreaded complication of bariatric surgery.
      The objective of this study was to describe the clinical presentation and
      outcomes of treatment in patients who develop anastomotic leaks after Roux-en-Y
      gastric bypass for obesity. STUDY DESIGN: Prospectively collected data on 3,018
      consecutive patients who underwent Roux-en-Y gastric bypass in 4 tertiary
      referral centers were reviewed. RESULTS: Sixty-three patients (2.1%) developed
      anastomotic leaks (open, 2.1%; laparoscopic, 2.1%) at a median of 3 days (range 0
      to 28 days) after Roux-en-Y gastric bypass. Symptoms and signs included
      tachycardia (72%), fever (63%), or abdominal pain (54%). Upper gastrointestinal
      series and CT demonstrated leaks in only 17 of 56 (30%) and 28 of 50 (56%)
      patients, respectively; when done jointly, both studies were negative in 30% of
      patients. The 68 anastomotic leaks occurred at the gastrojejunostomy (49%),
      excluded stomach (25%), jejunojejunostomy (13%), gastric pouch (9%), and
      uncertain location (4%). Forty patients (63%) required 58 reoperations for
      drainage of intraabdominal collections (55%), repair of anastomotic defects
      (34%), or revision of the leaking anastomosis (11%), with an overall morbidity of
      53% and mortality of 10%. Nonoperative treatment was successful in 23 of 26
      patients, with an overall morbidity of 61% and no mortality (p=NS versus
      operative). Operative treatment was more common in patients with hypotension or
      oliguria (p < 0.01). CONCLUSIONS: Lack of specificity in clinical presentation
      and imaging studies make diagnosing anastomotic leaks challenging, so operative
      exploration should be part of the diagnostic algorithm. Nonoperative treatment is
      safe and effective in a subset of patients who exhibit stable hemodynamic
      parameters and are known to have controlled leaks.

PMID- 17189113
TI  - Evaluation of the stapled transanal rectal resection technique with two staplers
      in the treatment of obstructive defecation syndrome.
AB  - BACKGROUND: This study was designed to assess the safety and effectiveness of
      stapled transanal rectal resection (STARR) and to compare the results of two
      staplers. STUDY DESIGN: From February 2001 to June 2005, 37 patients diagnosed
      with obstructive defecation syndrome were treated with the STARR technique. We
      analyzed variables related to the patient, diagnosis based on anorectal
      exploration, surgical technique used, and clinical and radiologic results. We
      compared these results in patients with procedure prolapsed hemorrhoids (PPH)33
      01 (group 1, n = 17) or PPH33-03 (group 2, n = 20). The patients were followed
      postoperatively at 1, 3, and 6 months, and annually. RESULTS: Intraoperative
      hemorrhage at the stapled suture occurred in 13 patients from group 1 and in 6
      patients from group 2 (p = 0.03). The degree of postoperative pain was not
      different between the two groups. During the followup period, radiologic and
      clinical correction of the rectocele and intussusception was found in 94.6% of
      the patients, with a recurrence in 1 patient from each group. One patient from
      group 1 developed stenosis of the anastomosis, which improved with digital
      dilatations. Six patients from group 1 and none from group 2 (p < 0.05) had
      granulomas on the staple line at the sites of the reabsorbable reinforcing
      stitches, which were related to postoperative bleeding and anal discomfort.
      CONCLUSIONS: STARR is an effective alternative for treatment of obstructive
      defecation syndrome, with a low morbidity and a shorter hospital stay. The use of
      PPH33-03 instead of PPH33-01 decreases the risk of hemorrhagic complications and
      enables more secure implantation as an outpatient procedure.

PMID- 17189114
TI  - Laryngeal reinnervation by ansa cervicalis nerve implantation for unilateral
      vocal cord paralysis in humans.
AB  - BACKGROUND: Ansa cervicalis (AC)-recurrent laryngeal nerve anastomosis (RLN) is
      usually not desirable for correction of paralytic dysphonia when it is difficult
      to find a viable distal stump of the recurrent laryngeal nerve. Nerve
      implantation of the thyroarytenoid muscle with the ansa cervicalis is a simple
      alternative method. STUDY DESIGN: Ten patients with unilateral vocal cord
      paralysis were prospectively designed to receive nerve implantation. A minimum
      period of 12 months after onset of paralysis was allowed to elapse to permit
      possible spontaneous reinnervation or compensation. Patients were followed long
      enough (at least 2 years) to determine if the procedure was successful. All
      patients were subjected to preoperative and postoperative voice recording,
      acoustic analysis, and videolaryngoscopy. Some of them underwent laryngeal
      electromyography. RESULTS: Ten patients underwent nerve implantation of the
      thyroarytenoid muscles by using the ansa cervicalis, and 8 of 10 (80%) had
      improved phonatory quality. Laryngeal electromyography showed that the procedure
      produced satisfactory reinnervation of the thyroarytenoid muscle. CONCLUSIONS:
      Nerve implantation of the thyroarytenoid muscle by the anso cervicalis is a
      simple and efficient alternative to nerve transfer if dense scarring at the
      cricothyroid articulation and lack of a viable distal stump of the recurrent
      laryngeal nerve preclude the procedure of nerve transfer. But careful selection
      of the appropriate candidate seems to be the earliest prerequisite for a
      successful procedure.

PMID- 17189115
TI  - The role of data and safety monitoring in acute trauma resuscitation research.
AB  - BACKGROUND: The role of data and safety monitoring boards (DSMBs) in clinical
      research in acute trauma resuscitation is not well documented. Many of the
      difficulties conducting acute resuscitation research are exacerbated because
      multiinstitutional studies are needed to adequately power such research. STUDY
      DESIGN: The purpose of the study was to demonstrate how a well-organized DSMB,
      explicitly required for these types of clinical trials by many funding agencies,
      can be a valuable resource in their safe and successful conduct by maximizing
      data integrity and striving to standardize care by monitoring the consistent and
      accurate collection of data and adherence to protocol. As an example, the work of
      an external DSMB in an international multicenter trial of recombinant activated
      coagulation factor VIIa (rFVIIa) in blunt and penetrating trauma patients is
      presented. The DSMB in this study was responsible for reviewing all serious
      adverse event (SAE) data, performing an extended review of SAEs, and reviewing
      results of analyses of 48-hour and 30-day mortality according to prespecified
      study stopping rules. RESULTS: Application by the DSMB of uniform definitions of
      SAEs substantially improved the integrity of the study data and facilitated
      analysis of events, such as disseminated coagulopathy, pulmonary complications,
      and multiple organ failure. As a result of the DSMB's efforts, important insights
      were gained to guide site selection and conduct of future trials of rFVIIa in
      trauma-induced hemorrhage. CONCLUSIONS: Based on our experience as members of the
      study DSMB and on a review of the literature, we recommend a strong role for
      DSMBs in multicenter trials in acute resuscitative care.

PMID- 17189116
TI  - Preliminary report of a prospective, randomized trial of underwater seal for
      spontaneous and iatrogenic pneumothorax.
AB  - BACKGROUND: Management of pneumothorax has traditionally been tube thoracostomy
      and -20 cm H2O suction. The purpose of our study was to determine if underwater
      seal in iatrogenic and spontaneous pneumothoraces is safe and efficacious and if
      small-caliber chest tubes are appropriate for routine use in pneumothorax. STUDY
      DESIGN: From April 2001 through October 2003 patients with iatrogenic or
      spontaneous pneumothorax were enrolled in this prospective, randomized trial.
      Small-bore catheters were inserted. Initial management was 1 hour -20 cm H2O
      suction, chest radiography, and randomization into -20 cm H2O suction, -10 cm H2O
      suction, or underwater seal. Tubes were discontinued at 48 hours if there were no
      pneumothoraces and no air leaks. Those with air leaks and recurrent
      pneumothoraces persisting 5 days underwent pleurodesis. The primary end point was
      successful chest tube removal at 48 hours. The secondary end point was need for
      pleurodesis. RESULTS: Twenty-nine patients were analyzed. Seven were randomized
      to -20 cm H2O suction, 11 to -10 cm H2O suction, and 11 to underwater seal. Most
      (59%, 17 of 29) chest tubes were successfully removed 48 hours after placement:
      57% (4 of 7) after -20 cm H2O suction, 73% (8 of 11) after -10 cm H2O suction,
      and 45% (5 of 11) after underwater seal (p = 0.48). Seven (24%) required
      pleurodesis: 29% (2 of 7) after -20 cm H2O suction, 27% (3 of 11) after -10 cm
      H2O suction, and 18% (2 of 11) after underwater seal (p = 0.70). CONCLUSIONS:
      Early underwater seal appears to be safe for treating iatrogenic and spontaneous
      pneumothoraces. It can achieve comparable frequencies of early chest tube removal
      and avoidance of operation compared with traditional management. A larger, multi
      institutional study should be performed to demonstrate that pneumothorax
      treatment can effectively incorporate small-caliber tubes and underwater seal.

PMID- 17189117
TI  - Minimally invasive parathyroidectomy using the lateral focused miniincision
      approach: Is there a learning curve for surgeons experienced in the open
      procedure?
AB  - BACKGROUND: Minimally invasive parathyroidectomy (MIP) has gained acceptance as
      the standard of care for management of primary hyperparathyroidism in which a
      single adenoma can be localized. The aim of this study was to determine if there
      is a learning curve for MIP using the lateral focused miniincision approach
      performed by surgeons experienced in open parathyroidectomy. STUDY DESIGN: This
      is a retrospective case series comprising all parathyroid operations undertaken
      by three surgeons in the University of Sydney Endocrine Surgical Unit from 2003
      to 2005. Outcomes of the experienced surgeon were compared with those of the two
      surgeons commencing practice. RESULTS: There were 699 parathyroidectomies
      performed in the Unit during the 36-month period (experienced surgeons: 438
      versus commencing physicians: 261). Of the parathyroidectomies performed, 57%
      done by experienced surgeons were minimally invasive compared with 38% of those
      performed by surgeons commencing practice (p < 0.001). There were no differences
      in the number of complications (p = 0.21), conversions to open exploration (p =
      0.6), and cure rates (p = 0.9) in the MIP patients in both groups. The initial
      (first 131 patients) and subsequent (next 130 patients) parathyroidectomy
      experiences of surgeons commencing practice were examined. In the initial
      experiences, 28% of the cases were minimally invasive compared with 48% in the
      subsequent experiences (p < 0.001). There were no differences in the number of
      complications (p = 0.3), conversions to open exploration (p = 0.9), and cure
      rates (p = 0.9). CONCLUSIONS: For surgeons experienced in open parathyroidectomy,
      there is no technical learning curve using the lateral focused miniincision
      technique for MIP. There is, however, a learning curve for patient selection.

PMID- 17189118
TI  - Impact of robotics and laparoscopy on surgical skills: A comparative study.
AB  - BACKGROUND: This study objectively surveyed and compared the ability of
      participants to perform laparoscopic and robotic tasks, and attempted to
      determine the key advantages of each modality. STUDY DESIGN: A task-based
      training course was developed that included laparoscopic and robotic task
      modules. Twenty-two participants (6 faculty members, 6 fellows, and 10 residents)
      completed a pretask and posttask questionnaire concerning 3 tasks, using both
      laparoscopy trainer and the daVinci robotic system (Intuitive Surgical, Inc). All
      tasks were timed and values were recorded. The surveys were completed by each
      participant to assess both pre- and posttask experiences. RESULTS: In the pretask
      survey, 55% of subjects reported participating in more than 20 laparoscopic
      cases, and only 27% had ever worked at a robotic console. The median number of
      beads threaded in 5 minutes was similar for the 2 methods, but the median time to
      complete 5 beads was 98 seconds for the laparoscope compared with 160 seconds
      using the robot (p = 0.001). The median number of loops completed in 5 minutes
      was greater (p < 0.001) using the robot (7.5 versus 2). Only 9% of subjects
      completed 9 loops in 5 minutes using the laparoscope; 50% did so using the robot
      (p < 0.05). The percentage of subjects completing 3 knots in 5 minutes was
      similar when using the laparoscope (45%) and robot (68%). Familiarity and tactile
      feedback were the primary advantages with laparoscopy, and EndoWrist (Intuitive
      Surgical, Inc) and stereoscopic visualization were perceived as advantages of the
      robot. CONCLUSIONS: As with any new technology, skills must be mastered to use
      robotic technology for the most benefit. The EndoWrist action and stereoscopic
      visualization were the most valued advantages of the robot. Most fellows and
      residents would seek additional training in robotics if given the opportunity.

PMID- 17189119
TI  - Hemorrhoidal disease: A comprehensive review.

PMID- 17189120
TI  - Surgical approach for hepatic caudate lobectomy: Review of 401 cases.

PMID- 17189121
TI  - Radiation injury and the surgeon.

PMID- 17189122
TI  - The role of carotid surgery in prevention of stroke in frail elderly patients.

PMID- 17189123
TI  - An international perspective on surgical health care and education.

PMID- 17189124
TI  - Surgical journal clubs: A bridge connecting experiential learning theory to
      clinical practice.

PMID- 17189125
TI  - Effective surgical residents strongly influence medical students to pursue
      surgical careers.
AB  - BACKGROUND: There is a paucity of data about the influence of surgical residents
      on the career choices of medical students. We hypothesized that medical students
      exposed to effective surgical residents would be more likely to pursue careers in
      surgery. STUDY DESIGN: From 1998 to 2003, 108 surgical residents were evaluated
      by medical students rotating on the third-year clerkship. Residents were scored
      on a 4-point scale (1 = outstanding to 4 = poor). The career choices of all
      medical students were also tabulated. RESULTS: We examined 2,632 evaluations on
      108 residents. Medical students who eventually pursued surgical residency
      training were exposed to surgical residents who were more effective clinical
      teachers, role models, and overall residents. In addition, medical students
      exposed to the highest-rated residents were more likely to pursue surgical
      residency training compared with students exposed to the least effective
      residents (12% versus 4.9%, p = 0.022). CONCLUSIONS: These data suggest that
      surgical residents who are effective educators and mentors influence medical
      students to pursue surgical careers. Efforts to provide more leadership and
      teaching workshops to surgical residents may not only create better future
      surgeon educators, but may also increase the number of students pursuing surgical
      training.

PMID- 17189126
TI  - A gunshot wound to the cervical spine: The case of the presidential assassin.

PMID- 17189127
TI  - Delayed right-sided diaphragmatic rupture and chronic herniation of unusual
      abdominal contents.

PMID- 17189128
TI  - Abdominal pain after uncomplicated laparoscopic appendectomy.

PMID- 17189129
TI  - Laparoscopic partial splenectomy.

PMID- 17189130
TI  - D-lactate and hepatic apoptosis: Is the D-isomer the major cause?

PMID- 17189131
TI  - Emergency tourniquets.

PMID- 17189134
TI  - Totally laparoscopic approach for treatment of early and advanced gastric cancer.

PMID- 17189136
TI  - Duodenal drainage during pancreas transplantation.

PMID- 17189137
TI  - Technique to prevent recurrence of lactiferous duct fistula.

PMID- 17189138
TI  - Open abdomen after trauma and abdominal sepsis.

PMID- 17189139
TI  - Avoiding misidentification injuries in laparoscopic cholecystectomy.

PMID- 17189142
TI  - Costenbader Lecture. The factor of time in retinopathy of prematurity.
AB  - PURPOSE: To analyze and discuss the relationship between the factor of time and
      our understanding of retinopathy of prematurity (ROP). METHODS: The author calls
      upon 30 years of experience in clinical investigations of ROP to critically
      synthesize selected literature on ROP, with attention to the broad theme of time.
      Future opportunities for clinical research are also considered. RESULTS: Although
      retinopathy of prematurity (ROP) ultimately is self-limited in its course, it is
      highly variable in its severity and outcome. Both the CRYO-ROP and the ETROP
      studies paid close attention to the chronology of ROP events; however, they
      approached the question of when to randomize eyes for treatment not simply
      according to a time definition, but rather according to disease severity
      characteristics. Still, results of both these studies can be reviewed from a time
      perspective, and indeed the pace of progression was one of the risk variables
      considered for ETROP randomization. The optimal schedule under which to perform
      eye examinations for active ROP is changing, as our understanding of this disease
      continues to improve. DISCUSSION: The factor of time is interwoven throughout the
      clinical course of ROP. Randomized clinical trials have proven to be an extremely
      efficient scientific method of comparing alternative treatment strategies. In
      looking toward the future, further randomized clinical trials are needed to
      investigate rational clinical management of cases in which retinal ablative
      therapy fails to arrest ROP's progression.

PMID- 17189144
TI  - Ocular complications of autoimmune polyendocrinopathy syndrome type 1.
AB  - PURPOSE: To report the ocular complications in a series of patients with
      autoimmune polyendocrinopathy syndrome, type 1 (APS1). METHODS: A retrospective
      study of 17 patients with APS1 syndrome treated at the department of
      ophthalmology, Our Lady's Hospital for Sick Children in Crumlin, Dublin, Ireland.
      All patients had clinical manifestations of the disease in keeping with the
      diagnostic criteria of APS1. Each patient had a comprehensive ophthalmic history
      taken and examination, including ocular symptoms, best-corrected visual acuity,
      slit-lamp biomicroscopy, tear film evaluation, and dilated ophthalmoscopic
      examination. RESULTS: Six of 17 patients (35%) had corneal changes. Two patients
      (12%) had severe keratoconjunctivitis requiring hospitalization and intensive
      topical steroids and lubricants. The inflammation resulted in visual acuity
      reduction in one patient secondary to central corneal scarring. Other ocular
      findings included reduced tear production, as tested with Schirmers tear strips
      (63%), lens opacities (18%), hypotrichosis (12%), hypertrichosis (5.9%),
      anisometropic amblyopia (5.9%), and myopia (5.9%). CONCLUSIONS: The most common
      and clinically important ocular manifestation of APS1 was keratoconjunctivitis
      associated with dry eye. This can result in progressive corneal scarring and
      vision loss.

PMID- 17189143
TI  - Random Dot E stereotest: testability and reliability in 3- to 5-year-old
      children.
AB  - PURPOSE: To determine the proportion of preschoolers testable with the Random Dot
      E (RDE) stereotest and the between-tester reliability. METHODS: Subjects were
      1257 3- to 5-year-olds who were participants in Head Start programs in five
      communities. The sample was over-weighted with children who failed the routine
      Head Start vision screening (58% failures; 42% nonfailures). Each child had
      stereotesting attempted by two licensed eye care professionals using the RDE
      test, first in a screening setting and later in a comprehensive eye examination.
      Pretesting was performed at 50 cm. Children who discriminated between the
      nonstereo E and blank cards on 4 of 4 or 4 of 5 presentations were considered
      testable. Stereotesting was conducted at 50, 100, and 150 cm corresponding to
      504, 252, and 168 arcsec disparity). Extent of agreement beyond chance between
      the screening and examination test results was assessed using the kappa (kappa)
      and weighted kappa (kappa(w)) statistics. RESULTS: Testability increased with age
      at both the first (86% of 3-, 89% of 4-, and 93% of 5-year-olds; p = 0.02) and
      the second (90% of 3-, 94% of 4-, and 98% of 5-year-olds; p = 0.0001) sessions.
      Overall, stereopsis was better at the second session. Agreement between sessions
      was moderate (kappa(w) = 0.43; 59% identical scores). While identical scores
      increased with age (53% of 3-, 59% of 4-, and 63% of 5-year-olds), kappa(w)
      statistics did not differ with age (p = 0.49). CONCLUSIONS: Child testability on
      the RDE stereotest was significantly better for older than younger preschool-age
      children. Overall, test-retest agreement was moderate and did not differ
      according to age. Testability rates of 98% and higher have been achieved in the
      same population with other screening tests including another random dot
      stereotest.

PMID- 17189145
TI  - Ocular abnormalities in Apert syndrome: genotype/phenotype correlations with
      fibroblast growth factor receptor type 2 mutations.
AB  - BACKGROUND/PURPOSE: Apert syndrome, a disorder of craniosynostosis, syndactyly,
      and other craniofacial malformations, is caused by point mutations (Ser252Trp or
      Pro253Arg) in the fibroblast growth factor receptor 2 gene. This study's goal was
      to determine ophthalmic phenotype/genotype correlations in patients with either
      mutation. METHODS: A retrospective chart review of demographic and ophthalmologic
      data was performed for 18 children carrying either the S252W (11) or the P253R
      (7) mutation. Fisher exact tests were performed to determine significance of
      variable phenotypes between the two mutation groups. RESULTS: In the P253R group,
      85% had strabismus (14% required surgery), 71% had ptosis, 43% had amblyopia, 14%
      had nasolacrimal duct obstruction, 14% had myopia, 14% had hyperopia, and 14% had
      astigmatism. In the S252W group, 91% had strabismus (64% required surgery), 73%
      had ptosis, 73% had amblyopia, 100% had nasolacrimal duct obstruction, 36% had
      myopia, 9% had hyperopia, and 82% had astigmatism. Overall, S252W and P253R
      groups showed significantly different numbers of patients with strabismus
      requiring surgery (p = 0.039), superior rectus muscle underaction (p = 0.024),
      nasolacrimal duct obstruction (p = 0.0002), and astigmatism (p = 0.005).
      CONCLUSIONS: Compared with patients with the P253R mutation, Apert syndrome
      patients with the S252W mutation may have more severe ocular phenotypes with a
      higher likelihood of developing strabismus, especially vertical deviation. They
      also are more likely to develop astigmatic refractive errors and tearing
      secondary to nasolacrimal system anomalies.

PMID- 17189146
TI  - Assessment of change of optic nerve head cupping in pediatric glaucoma using the
      RetCam 120.
AB  - PURPOSE: To ascertain the interobserver agreement among various specialists when
      analyzing images of the optic nerve head taken with the RetCam 120 (Clarity
      Medical Systems, Inc., Pleasanton, CA) for assessing the progression of optic
      disk cupping in pediatric glaucoma. METHODS: Five observers compared pairs of
      RetCam 120 two-dimensional photographs from 64 eyes to identify whether or not
      changes in the optic disk had occurred. Observers included a pediatric glaucoma
      specialist, pediatric neurophthalmologist, strabismologist, pediatric ophthalmic
      imaging specialist, and pediatric ophthalmology fellow. Each was masked to the
      patient identity and clinical course. For each patient, the observers reviewed
      the photographs taken prior to therapy and at a minimum of 6 months following
      initiation of therapy. Interobserver variability was calculated and analysis
      conducted to identify influential variables. RESULTS: Poor agreement was noted
      between the observers. No significant association was obtained between agreement
      level and variables affecting photographic quality: variability of contrast and
      illumination, exposure and magnification, image clarity, presence of fluorescein
      on the cornea, and pixelation of the image with poor resolution. Raters noted
      problems with these image variables in 75.6% of the observations. The Kappa
      statistic obtained was kappa = 0.29 with overall proportion of agreement of p =
      0.69, suggesting a fair agreement but not a moderate agreement. CONCLUSIONS:
      Comparison of RetCam 120 pediatric optic nerve head photographs, when performed
      subjectively by observers with different perspectives, and in isolation from
      clinical information, may not be a reliable indicator of cupping change. In
      addition, variations in image contrast, luminance, color, and pixelation pose
      significant challenges to agreement between observers. Comparison of RetCam 120
      images should not be considered the sole criterion for monitoring pediatric
      glaucoma.

PMID- 17189147
TI  - Orbital optic nerve gliomas in children with neurofibromatosis type 1.
AB  - PURPOSE: To describe the clinical course and treatment of symptomatic orbital
      optic nerve gliomas in children with neurofibromatosis type-1 (NF-1). METHODS: A
      retrospective review of the records of patients with NF-1 and symptomatic orbital
      optic nerve gliomas seen in a large multidisciplinary NF-1 clinic of a tertiary
      care children's hospital. The main outcome measures included presenting symptoms
      and signs, ophthalmologic examination at diagnosis, the presence of progressive
      disease following diagnosis, type of therapy, and the reasons therapy was
      instituted. RESULTS: Twelve patients with symptomatic orbital optic nerve
      gliomas, all of which led to proptosis (eight girls, four boys), were identified.
      The mean age of diagnosis of NF-1 was 20 months; the mean age of diagnosis of the
      orbital optic nerve glioma was 26 months. At the time of diagnosis of the tumor,
      10 of 12 patients (83%) had decreased visual acuity in the affected eye. Three
      patients underwent optic nerve resection; eight received chemotherapy, and one
      was observed without therapy. Of the eight children who received chemotherapy,
      progressive disease prior to treatment could be documented in only three; none of
      these eight children had a reproducible improvement in vision following
      chemotherapy. There was no demonstrable improvement in vision in any treated
      patient with NF-1-associated orbital optic nerve gliomas. CONCLUSIONS: Although
      not definitively proven, our data and previous studies suggest that NF-1
      associated orbital optic nerve gliomas should not be treated unless there is
      clear evidence of either ophthalmologic or radiographic progression. Surgical
      excision of tumors which have led to proptotic eyes without functional vision
      should be reserved for cosmetic purposes or to treat complications of exposed
      globes.

PMID- 17189148
TI  - Decreased cortical activation in response to a motion stimulus in anisometropic
      amblyopic eyes using functional magnetic resonance imaging.
AB  - PURPOSE: Motion perception abnormalities and extrastriate abnormalities have been
      suggested in amblyopia. Functional MRI (fMRI) and motion stimuli were used to
      study whether interocular differences in activation are detectable in motion
      sensitive cortical areas in patients with anisometropic amblyopia. METHODS: We
      performed fMRI at 1.5 T 4 control subjects (20/20 OU), 1 with monocular
      suppression (20/25), and 2 with anisometropic amblyopia (20/60, 20/800).
      Monocular suppression was thought to be form fruste of amblyopia. The
      experimental stimulus consisted of expanding and contracting concentric rings,
      whereas the control condition consisted of stationary concentric rings.
      Activation was determined by contrasting the 2 conditions for each eye. RESULTS:
      Significant fMRI activation and comparable right and left eye activation was
      found in V3a and V5 in all control subjects (Average z-values in L vs R contrast
      0.42, 0.43) and in the subject with monocular suppression (z = 0.19). The
      anisometropes exhibited decreased extrastriate activation in their amblyopic eyes
      compared with the fellow eyes (zs = 2.12, 2.76). CONCLUSIONS: Our data suggest
      motion-sensitive cortical structures may be less active when anisometropic
      amblyopic eyes are stimulated with moving rings. These results support the
      hypothesis that extrastriate cortex is affected in anisometropic amblyopia.
      Although suggestive of a magnocellular defect, the exact mechanism is unclear.

PMID- 17189149
TI  - Teller Acuity Card norms with and without use of a testing stage.
AB  - PURPOSE: To determine whether norms obtained using the Teller Acuity Card stage
      are appropriate for comparison with results obtained when the stage is not used.
      METHODS: Eighty children were tested, 20 each at 3.5, 11, 17, and 30 months of
      age. Binocular grating acuity was measured once with Teller Acuity Cards
      presented with the stage and once without the stage. Test order was
      counterbalanced across subjects. Testers were aware that gratings progressed from
      lower to higher spatial frequencies, but were masked to the absolute spatial
      frequency of the grating on each card. Testers were masked to acuity results
      until the child completed testing. RESULTS: Repeated measures ANOVA with age as a
      between-subjects variable and test setting as a within-subjects variable showed a
      significant effect of age (p < 0.001) and test setting (p < 0.001), and a
      significant interaction between age and test setting (p < 0.01). Post-hoc
      comparisons (with Bonferroni correction) showed that the difference in acuity
      results obtained with the stage versus without the stage was significant at 17
      months (p < 0.05), but not at 3.5, 11, or 30 months. CONCLUSIONS: Grating acuity
      norms obtained with the Teller Acuity Card stage are appropriate for comparison
      with data obtained without the stage in children 3.5, 11, and 30 months of age.
      However, when 17-month-old children are tested without the stage, comparison of
      results with norms obtained with the stage is problematic, because testing
      without the stage results in reduced acuity scores in this age group.

PMID- 17189151
TI  - Maximum motor fusion combined with one-hour preoperative prism adaptation test in
      patients with acquired esotropia.
AB  - PURPOSE: Preoperative prism adaptation and the maximum motor fusion test reduce
      the risk of postoperative undercorrection, overcorrection, and bifocal
      requirements in acquired esotropia. The purpose of our study is to determine the
      efficacy of the maximum motor fusion test followed by a short prism adaptation
      test in patients with acquired esotropia undergoing bilateral medial rectus
      muscle recession. METHODS: We undertook a retrospective review of 29 subjects
      with acquired esotropia without history of amblyopia, previous strabismus
      surgery, use of bifocals, pattern anisotropia, dissociated vertical deviation, or
      oblique muscle dysfunction. All subjects underwent bilateral medial rectus muscle
      recessions based on the distance angle of deviation measured with the maximum
      motor fusion test followed by prism adaptation test. Alternate prism and cover
      testing was performed after 1 hour of prism adaptation to determine the angle of
      deviation for surgical correction. RESULTS: The age at surgery was 4.5 +/- 1
      years. The preoperative angle of deviation at distance was 20.4 +/- 4.2(delta).
      It increased to 36.2 +/- 4.2(delta) after the maximum motor fusion test followed
      by 1 hour of prism adaptation testing. The final preoperative angle of deviation
      post motor fusion test-prism adaptation test was significantly larger than the
      initial angle of deviation (p < 0.0001). The final postoperative deviation at
      distance was 1.3 +/- 3.3(delta), and 5.2 +/- 1.5(delta) at near. Postoperative
      follow up was 18 +/- 2.6 months (range, 13-24 months). CONCLUSIONS: The
      combination of maximum motor fusion and preoperative prism adaptation allowed
      increased amounts of medial rectus muscle muscle recession, decreasing the risk
      of postoperative undercorrection without increasing the risk of overcorrection.

PMID- 17189150
TI  - Effects of tenotomy on patients with infantile nystagmus syndrome: foveation
      improvement over a broadened visual field.
AB  - PURPOSE: To investigate the effects of four-muscle tenotomy on visual function
      and gaze angle in patients with infantile nystagmus syndrome (INS). METHODS: Eye
      movements of nine patients with infantile nystagmus were recorded using infrared
      reflection or high-speed digital video techniques. Experimental protocols were
      designed to record the patients' eye-movement waveforms, pre- and post-tenotomy,
      at different gaze angles. We used the eXpanded Nystagmus Acuity Function (NAFX)
      to measure tenotomy-induced changes in the nystagmus at primary position and
      various gaze angles. The longest foveation domains (LFD) were measured from
      fitted curves. Peak-to-peak nystagmus amplitudes and foveation-period durations
      were also measured. All measurements were made unmasked. RESULTS: All seven
      patients with narrow, high-NAFX, gaze-angle regions showed broadening of these
      regions of higher visual function. Three patients showed moderate NAFX
      improvement (13.9-32.6%) at primary position, five showed large improvement (39.9
      162.4%), and one showed no NAFX change (due to his high pretenotomy NAFX).
      Primary position measured acuities improved in six patients. All patients had
      reductions in nystagmus amplitudes ranging from 14.6 to 37%. The duration of the
      foveation period increased in all nine patients (11.2-200%). The percentage
      improvements in both the NAFX and the LFD decreased with higher pretenotomy
      values. CONCLUSIONS: In addition to elevating primary position NAFX, tenotomy
      also broadens the high-NAFX regions. This broadening effect is more prominent in
      patients who had sharp pretenotomy NAFX peaks. Four-muscle tenotomy produces
      higher primary position NAFX increases in infantile nystagmus patients whose
      pretenotomy values are relatively low, with the improvement decreasing at higher
      pretenotomy values. The tenotomy procedure improves visual function beyond
      primary position acuity. This extends the utility of surgical therapy to several
      different classes of patients with INS for whom other procedures are
      contraindicated. The pretenotomy NAFX can now be used to predict both primary
      position acuity improvements and broadening of a patient's high-NAFX range of
      gaze angles.

PMID- 17189152
TI  - "Inverted Brown pattern": a tight inferior oblique muscle masquerading as a
      superior oblique muscle underaction--clinical characteristics and surgical
      management.
AB  - PURPOSE: To characterize, and evaluate the surgical management of, patients with
      unilateral deficiency of depression in adduction, suggesting superior oblique
      muscle underaction, without significant ipsilateral inferior oblique muscle
      overaction. METHODS: Such patients were identified who also had received either
      ipsilateral inferior oblique (IO) muscle weakening or contralateral inferior
      rectus muscle recession. Their histories, motility patterns, intraoperative
      findings, types of strabismus surgery, and postoperative results were analyzed.
      RESULTS: Twelve patients were identified with unilateral deficiency of depression
      in adduction, with no or minimal ipsilateral IO muscle overaction. Three of these
      patients (25%) had previously had surgery for Brown syndrome. Four (33%) had
      prior orbital floor trauma. On exaggerated forced duction testing recorded for
      nine patients, a tight IO muscle was recorded in 78%, with no laxity of the
      superior oblique tendon. Four patients (33%) underwent contralateral inferior
      rectus muscle recession, but in all four the deficiency of depression in
      adduction recurred. The other eight (67%) had an IO muscle weakening procedure
      and achieved overall improvement of ocular alignment. Nine subsequent patients
      with a similar pattern of misalignment were each managed with an IO weakening
      procedure, with good results. CONCLUSIONS: This motility pattern, which we are
      calling an "inverted Brown pattern," is caused by a tight or inelastic IO muscle.
      In such cases, IO muscle weakening yields better results than contralateral
      inferior rectus muscle recession, even though there is no significant IO muscle
      overaction preoperatively.

PMID- 17189153
TI  - Adjustment of the surgical nomogram for surgery on slipped extraocular muscles.
AB  - PURPOSE: A slipped muscle is an underdiagnosed complication of strabismus
      surgery. Surgery necessitates intraoperative diagnosis, measurement, and
      resection of the empty sheath. We analyzed the results of empty sheath surgery
      for slipped medial and lateral rectus muscles in a large cohort of patients.
      METHODS: Eighty-five patients who underwent empty sheath surgery at a secondary
      referral center by a single strabismologist were included in the study. We
      retrospectively analyzed the preoperative and postoperative change in angle of
      deviation 6 weeks after surgery. All cases were reoperations in which an
      unexpected or unsatisfactory outcome followed primary surgery. Consecutive
      exotropias with slipped medial rectus muscles were noted in 68 patients. There
      were 17 esotropia cases with lateral rectus muscles slip, of which 2 were
      consecutive exotropias that became consecutive esotropias. Bilateral medial
      rectus muscle slips were found in 6 patients with consecutive exotropias.
      Adjustable suture surgery was performed in 27 patients. RESULTS: Resection of the
      empty sheath of the slipped medial or lateral rectus muscle with advancement to
      the original site of insertion was done in all cases; in addition, the antagonist
      muscle was recessed only if it was tight. The total muscle advancement was
      calculated in millimeters from the total amount of sheath resected, muscle
      advanced, and the antagonist recessed. The greater the preoperative deviation,
      the more surgical muscle advancement was required and the greater the change in
      postoperative angle of deviation. Mean change in angle of deviation was
      3.13(delta) for each millimeter of muscle advancement (median = 3.00, SD = 1.72).
      CONCLUSIONS: The diagnosis of slipped muscle should be confirmed during
      strabismus surgery. The empty sheath was measured, resected, and the muscle
      advanced to the original site of insertion. An approximate 3(delta) change in
      angle of deviation was observed for every millimeter of muscle of advancement.
      For very large and very small deviations, surgeons should modify this to an
      accustomed measurement dictated by their experience.

PMID- 17189154
TI  - Bilateral congenital lacrimal sac fistulae in a patient with ectrodactyly
      ectodermal dysplasia-clefting syndrome.
AB  - We describe a case of bilateral congenital lacrimal sac fistulas, associated with
      ectrodactyly-ectodermal dysplasia-clefting syndrome. The embryologic basis for
      this condition is discussed, as well as the epidemiology, typical presentation,
      and possible treatment modalities. After we excised the fistulas and intubated
      the nasolacrimal ducts in this patient, he experienced improvement in symptoms by
      report.

PMID- 17189155
TI  - Subclinical endophthalmitis following a rooster attack.
AB  - Ocular injury resulting from rooster attacks is rarely reported in the
      literature. Sadly, the target of these attacks is most often children younger
      than 3 years old, whose naivete of the aggressive, territorial behavior of birds
      can place them at risk. Acute sequelae of these attacks can result in a lifetime
      of visual impairment. The possibility of a subacute or occult infection is an
      unusual occurrence that must always be considered. In an effort to prevent future
      attacks and ocular casualties, we present a case of a 12-month-old boy who
      suffered an open globe following a rooster attack. The open globe was emergently
      repaired. One week later, a white cataract was noticed on examination in the
      absence of systemic or ocular signs of inflammation. Traumatic endophthalmitis
      and lenticular abscess were suspected during examination under anesthesia.
      Vitrectomy, lensectomy, and injection of intravitreal antibiotics were performed.
      Culture of lenticular and vitreous aspirates grew alpha-streptococcus. Alpha
      streptococcal endophthalmitis can result from ocular injuries caused by rooster
      pecking. The infection may present insidiously and without typical ocular or
      systemic symptoms or signs. Management is challenging and may require surgery.

PMID- 17189156
TI  - Acute acquired comitant esotropia after orbital cellulitis.
AB  - Acute extraocular muscle restriction in children is a rare condition; orbital
      myositis is the most common cause. Most neuropathic or myopathic causes of
      strabismus present as an incomitant deviation. We report a case of orbital
      cellulitis preceding acute comitant esotropia in a patient showing no evidence of
      myositis or neurologic pathology.

PMID- 17189158
TI  - Periocular dermatitis artefacta in a child.
AB  - Dermatitis artifacta is a factitious dermatological disorder with many forms of
      presentation in any part of the body. It is commonly documented in dermatological
      cases but rarely presented as an ophthalmic condition. The diagnosis of
      dermatitis artifacta is often concluded after rigorous and repeated
      investigation. Histological sampling of skin lesions is usually required in these
      cases to exclude masquerading skin lesions such as basal cell carcinoma,
      vasculitis, or herpetic skin lesions.

PMID- 17189157
TI  - Community-acquired methicillin-resistant Staphylococcus aureus in association
      with chronic dacryocystitis secondary to congenital nasolacrimal duct
      obstruction.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as an important
      pathogen responsible for serious ocular and systemic disease. MRSA has been
      reported to occur in dacryocystitis in the adult population. This is the first
      case report of community-acquired MRSA in the pediatric population in association
      with chronic dacryocystitis secondary to congenital nasolacrimal duct obstruction
      in an infant.

PMID- 17189159
TI  - Amblyopia in the phakic eye after unilateral congenital cataract extraction.
AB  - The treatment of unilateral congenital cataract remains a challenge because form
      deprivation early in life leads to amblyopia. Visual outcomes after congenital
      cataract extraction have improved dramatically with earlier surgery, greater
      attention to optical correction of the aphakia, and part-time occlusion therapy
      of the phakic eye. A published review of unilateral congenital cataract studies
      between 1988 and 2004 found that 88% of patients with primary intraocular lens
      implantation achieved 20/200 or better visual acuity and a mean of 20% achieved
      20/40 or better visual acuity. Improved outcomes are attributable, in part, to
      surgical intervention at an earlier age. It has been shown that surgical
      intervention during the first 6 weeks of age is associated with a better visual
      prognosis than surgery at a later age. In this report, we describe a patient with
      unilateral congenital cataract treated with cataract extraction and intraocular
      lens implantation at 8 weeks of age who had a better visual outcome in his
      operative eye than in his phakic eye.

PMID- 17189160
TI  - Management of congenital unilateral proptosis from an orbital epithelial cyst by
      cyst aspiration.
AB  - A rare cause of axial proptosis, orbital epithelial cysts are presumed to be of
      conjunctival origin if the wall is composed of nonkeratinized squamous epithelium
      (especially if goblet cells are present). These cysts can occur at any age and
      are typically surgically resected if symptomatic. The subject of this report is
      the management of a congenital orbital epithelial cyst by needle aspiration in a
      newborn with ipsilateral esotropia and severe unilateral proptosis.

PMID- 17189161
TI  - Anteriorization of inferior oblique muscle and downward transposition of medial
      rectus muscle for lost inferior rectus muscle.
AB  - A 6-year-old boy who had been treated with bilateral medial rectus muscle
      recessions 3 years earlier for congenital esotropia was undergoing bilateral
      inferior oblique muscle recessions to correct inferior oblique muscle overaction.
      The right inferior rectus muscle was inadvertently cut during this surgery and
      was irretrievable. To manage this complication, the medial rectus muscle was
      transposed toward the inferior rectus insertion and the inferior oblique muscle
      was anteriorized. At the 1 year follow-up visit, no infraduction deficit was
      present on downgaze and only 8(delta) of left hypertropia was present in primary
      position.

PMID- 17189162
TI  - Retrobulbar hemorrhage following strabismus surgery.
AB  - Retrobulbar hemorrhage, although a well-known complication of retrobulbar
      injection, periocular injections, and periocular surgeries, is not routinely
      associated with strabismus surgery. We present a case of delayed orbital
      hemorrhage occurring in a young boy 2 days after strabismus surgery.

PMID- 17189163
TI  - Surgical treatment for progressive esotropia in the setting of high-axial myopia.
AB  - Acquired esotropia in association with high myopia may be secondary to
      displacement of the lateral rectus muscle pulley system or to the mechanical
      restriction due to the contact between the posterior elongated globe and the
      orbital apex limiting rotation. We present the clinical findings and surgical
      management of a patient with this condition.

PMID- 17189164
TI  - Developments in biotechnological production of sweet proteins.
AB  - Most proteins are tasteless and flavorless, while some proteins elicit a sweet
      taste response on the human palate. Six proteins, thaumatin, monellin, mabinlin,
      brazzein, egg lysozyme, and neoculin (previously considered as curculin) have
      been identified as sweet-tasting proteins. However, no common features among them
      have been observed. Herein, recent advances in the research of sweet-tasting
      proteins and the production of such proteins by biotechnological approaches are
      reviewed. Information on the structure-sweetness relationship for these proteins
      would help not only in the clarification of the mechanism of interaction of sweet
      tasting proteins with their receptors, but also in the design of more effective
      low-calorie sweeteners.

PMID- 17189165
TI  - ZMVHA-B1, the gene for subunit B of vacuolar H+-ATPase from the eelgrass Zostera
      marina L. Is able to replace vma2 in a yeast null mutant.
AB  - A vacuolar H(+)-ATPase (VHA) gene (ZMVHA-B1) was isolated from an eelgrass
      (Zostera marina) leaf cDNA library and was characterized to be approximately 1.4
      kbp in length and to encode the B subunit protein of VHA comprising 488 amino
      acids. ZMVHA-B1 was highly expressed in all organs of eelgrass; the expression
      level was highest in the leaves. On transformation of a yeast vma2 null mutant
      with ZMVHA-B1, yeast cells became able to grow at pH 7.5, accompanied by the
      vesicular accumulation of LysoSensor green DND-189. Thus, ZMVHA-B1 expressed in
      yeast cells produced a functional B subunit that was efficiently incorporated
      into the VHA complex and eventually restored vacuolar morphology and activity.
      This success expedites the application of heterologous expression in yeast mutant
      cells to the screening of eelgrass genes involved in salt-resistance mechanisms,
      which are to be utilized in improving important crops.

PMID- 17189166
TI  - Establishment of ovarian reconstruction system in culture for functional genomic
      analysis.
AB  - In a previous study, we reported a list of genes expressed differentially in
      primordial and primary follicles [Park et al., Fertil. Steril., 83, 410-418
      (2005)]. An innovative experimental system is required to evaluate the functions
      of these genes in folliculogenesis, particularly primordial-primary follicle
      transition. In this study, ovarian tissues were dissociated, and isolated cells
      were transfected using small interfering RNAs (siRNAs) for disrupting a specific
      gene, followed by ovarian reconstruction via calcium alginate encapsulation. The
      effects of RNA interference (RNAi) on follicular development were evaluated by a
      histological observation of the reconstructed ovarian tissue. Interestingly,
      follicular formation and development showed differences between control and
      experimental groups. Thus, even though this system includes some problems that
      need to be solved, ovarian reconstruction following the modification of gene
      expression of individual ovarian component cells could lead the way to methods of
      studying molecular mechanisms of primordial-primary follicle transition.

PMID- 17189167
TI  - Biological responses of ligament fibroblasts and gene expression profiling on
      micropatterned silicone substrates subjected to mechanical stimuli.
AB  - In this study, ligament fibroblasts were cultivated on micropatterned silicone
      substrates and subjected to cyclic stretching to simulate the in vivo
      biomechanical environment during ligament healing. Without stretching, ligament
      fibroblasts were aligned parallel to the microgrooves on the silicone substrate
      surface. However, we previously reported that uniaxial cyclic stretching induces
      alignment perpendicular to the stretching axis. With stretching on a microgrooved
      surface, cell proliferation and collagen production were greatly enhanced. The
      exact functions of the micropatterned surface and mechanical stimuli are unknown.
      Therefore, in gene expression microarray experiments, genes whose expression is
      inhibited by subculture from passage 0 (P0) to passage 8 (P8) and enhanced by
      micropatterning and stretching were sought out. The following six genes were
      selected: MGP, GADD45A, UNC5B, TGFB1, COL4A1, and COL4A2. The selected genes play
      fundamental roles in cell proliferation, differentiation, apoptosis, and
      structural maintenance. On the basis of the obtained gene expression profiles, we
      identified candidate genes that might be involved in responses to a
      micropatterned surface and mechanical stretching.

PMID- 17189168
TI  - Precise metabolic flux analysis of coryneform bacteria by gas chromatography-mass
      spectrometry and verification by nuclear magnetic resonance.
AB  - Precise metabolic flux analysis (MFA) by gas chromatography-mass spectrometry (GC
      MS) and computer calculation was performed, and the consistency of the estimated
      results was verified by independently performed nuclear magnetic resonance (NMR)
      analysis. The precise estimation of flux by the integration method of the mass
      isotopomer signal, defined as the coefficient of variance (CV) of multiple
      determination, was investigated, and the results estimated using different data
      sets with the same magnitude of error were confirmed. The CV of multiple
      determinations was sufficiently small to discuss and compare the fluxes of a
      metabolic pathway. The estimated fluxes using the GC-MS data were cross-validated
      with the NMR data that were independently measured and not used for MFA. The
      developed method was successfully applied to the MFA of the growth phase of two
      different glutamate-producing coryneform bacteria, Corynebacterium glutamicum and
      C. efficiens. The difference in the growth rate between these two bacterial
      species was discussed while considering the results of MFA, including forward and
      backward (exchange) fluxes.

PMID- 17189169
TI  - Modified keratin sponge: binding of bone morphogenetic protein-2 and osteoblast
      differentiation.
AB  - A keratin sponge was chemically modified to obtain carboxyl and amino sponges by
      the alkylation of a large amount of active SH group on keratin proteins with
      iodoacetic acid and 2-bromoethylamine, respectively. The carboxyl sponge having a
      large amount of carboxyl group was a scaffold that could bind significant amounts
      of basic bioactive proteins, such as lysozyme and bone morphogenetic protein
      (BMP)-2, and drugs. Lysozyme (maximum 3.7 mg), a model of basic cytokines such as
      BMP-2, was absorbed by the carboxyl sponge (4.8 mg), but not by the amino sponge.
      The lysozyme was rapidly released from the carboxyl sponge in a buffer containing
      at a concentration higher than 0.5 M, but at 0.15 M, near the physiological ionic
      strength, after initial burst (only 11%), no significant release was observed
      (15%, 48 h). BMP-2 also bound the carboxyl sponge. The preosteoblast cells grown
      inside the BMP-2-loaded sponge differentiated, whereas those grown outside the
      sponge did not, suggesting that no significant amount of BMP-2 leaked into the
      surrounding media. The effects of BMP-2 were confined inside modified keratin
      sponge. Therefore, using in vivo, we expect that only internal osteogenesis will
      be induced and that no external heterotopis ossification will be induced.

PMID- 17189170
TI  - Cultivation of recombinant Chinese hamster ovary cells grown as suspended
      aggregates in stirred vessels.
AB  - Recombinant Chinese hamster ovary (rCHO) cells capable of producing a
      prourokinase mutant (mPro-uk) grown as suspended aggregates in stirred vessels
      were described and characterized. The addition of chitosan to a mixture of DMEM
      and Ham's F12 (D-MEM/F-12) medium promoted cell aggregation and spheroid
      formation efficiently. Multicellular aggregates formed immediately after the rCHO
      cells were inoculated into the chitosan-added medium, and the mean diameter of
      the cell aggregates reflecting the aggregate size increased with culture time,
      shifting from 65 to 163 mum after 2 and 9 d of culture in spinner flasks. No
      significant difference in the metabolism performance of the rCHO cells was
      observed between suspended aggregates and anchored monolayers. However, the cells
      cultured as suspended aggregates showed a marked decrease in growth rate as
      evaluated from specific growth rate (mu). Replacing D-MEM/F-12 medium with CD 293
      medium caused compact spherical cell aggregates to dissociate into small
      irregular aggregates and single cells without apparent effects on cell
      performance in subcultures. The perfusion culture of the rCHO cells grown as
      suspended aggregates in a 2-l stirred tank bioreactor for 15 d resulted in a
      maximum viable cell density of 5.6 x 10(6) cells ml(-1) and an mPro-uk
      concentration of about 2.6 x 10(3) IU ml(-1), and cell viability was remained at
      roughly 90% during the entire run.

PMID- 17189171
TI  - Novel substrate specificity of D-arabinose isomerase from Klebsiella pneumoniae
      and its application to production of D-altrose from D-psicose.
AB  - d-Arabinose isomerase from Klebsiella pneumoniae 40bXX was purified 12-fold with
      a 62.5% yield indicated by its electrophoretic homogeneity. The purified enzyme
      showed the highest activities toward d-arabinose and l-fucose as substrates at
      optimum conditions (50 mM glycine-NaOH, pH 9.0, 40 degrees C). The enzyme had a
      broad range of substrate specificities toward various d/l-aldoses, i.e., d
      arabinose, l-fucose, d/l-xylose, d-mannose, d/l-lyxose, l-glucose, d-altrose and
      d/l-galactose. The equilibrium ratios between d-arabinose and d-ribulose, l
      fucose and l-fuculose, d-altrose and d-psicose, and l-galactose and l-tagatose
      were 90:10, 90:10, 13:87 and 25:75, respectively. Using a combination of the
      immobilized d-tagatose 3-epimerase and d-arabinose isomerase, we achieved the
      production of d-altrose from d-fructose in a batch reactor. We successfully
      produced approximately 12 g of d-altrose from 200 g of d-fructose in a reaction
      series with an overall yield of 6%. The product obtained was confirmed to be d
      altrose by HPLC and (13)C-NMR. To the best of our knowledge, this is the first
      report on the production of d-altrose from a cheap sugar, d-fructose, using an
      enzymatic method.

PMID- 17189172
TI  - Effect of flashing light from blue light emitting diodes on cell growth and
      astaxanthin production of Haematococcus pluvialis.
AB  - To conserve energy in the production of astaxanthin by the green alga
      Haematococcus pluvialis, we utilized intermittent flashing light from blue light
      emitting diodes (LEDs) and investigated the effects of the incident light
      intensity (2-12 micromol m(-2) s(-1)), duty cycle (17-67%) and frequency (25-200
      Hz) of flashing on the cell growth and astaxanthin production. In the above
      ranges, the final astaxanthin concentration under illumination by flashing light
      was significantly higher than that obtained under illumination with continuous
      light at the same incident intensity. For example, flashing light at an incident
      intensity of 8 micromol m(-2) s(-1) gave the same final astaxanthin concentration
      that was obtained under continuous light illumination at 12 micromol m(-2) s(-1),
      thus reducing energy consumption by 1/3. We therefore conclude that flashing
      light from blue LEDs is a promising illumination method for indoor algal
      cultivation using photobioreactors.

PMID- 17189173
TI  - Glycosylation variant analysis of recombinant human tissue plasminogen activator
      produced in urea-cycle-enzyme-expressing Chinese hamster ovary (CHO) cell line.
AB  - Tissue plasminogen activator (tPA) was produced in ornithine transcarbamoylase
      (OTC) cells by introducing the tPA gene into OTC cells. OTC cells were originally
      derived from Chinese hamster ovary (CHO) cells and express the first two enzymes
      of the urea cycle, carbamoyl phosphate synthetase I (CPS I) and OTC. To
      investigate glycosylation variants, tPA variants produced in serum-supplemented
      culture medium of OTC-tPA cells were separated by lysine-Sepharose 4B
      chromatography. Unlike in previous studies that used lysine-Sepharose
      chromatography, two peaks were identified to correspond to eluted glycosylation
      variants type I and II and type II and the percentages of the type I and type II
      variants were found to be 23% and 77%, respectively. The biological activities of
      the type I and II and type II variants were twofold that of the Third
      International tPA Standard (98/714) produced in the CHO cell line, and the
      activity of type II variant was 12.6% higher than that of the type I and II
      variants. These results demonstrate that tPA produced in urea-cycle-enzyme
      producing OTC cells have a very high biological activity and the percentage of
      type II variant which is very valuable for the biopharmaceutical industry is
      higher than that of any report using CHO cells.

PMID- 17189174
TI  - Determination of enzymes from Colletotrichum sp. AHU9748 essential for
      lepidimoide production from okra polysaccharide.
AB  - The allelopathic substance lepidimoide (Lp), which exhibits multiple functions in
      the growth and development of plants, was produced by Colletotrichum sp. AHU9748
      from okra polysaccharide. Okra polysaccharide has the repeating structure (1-->4)
      O-alpha-(d-galactopyranosyluronic acid)-(1-->2)-O-alpha-l-rhamnopyranose in its
      hexasaccharide repeating unit of its main chain. To determine the enzymes
      essential for Lp production, the supernatant of a culture broth was fractionated
      by repeated column chromatographies to identify two serial fractions responsible
      for Lp production and non-Lp production by measuring Lp production together with
      beta-galactosidase (beta-gal), rhamnogalacturonan lyase (RG-lyase) and
      acetylesterase (AE) activities, which we hypothesized to be necessary for Lp
      production from the structure of Lp. We confirmed the presence of these three
      enzymatic activities in the highest-Lp-producing fraction. The addition of
      purified RG-lyase to fractions producing no or a small amount of Lp demonstrated
      that beta-gal and RG-lyase activities are necessary for Lp production. The N
      terminal amino acid sequences of the three separated proteins on SDS-PAGE
      confirmed the presence of enzymes identical to beta-gal, RG-lyase and AE in the
      Lp-producing fractions.

PMID- 17189175
TI  - Involvement of radical species in inactivation of Vibrio parahaemolyticus in
      saline solutions by direct-current electric treatment.
AB  - The effect of pulsed low-direct-current (DC) electric treatment on the viability
      of Vibrio parahaemolyticus in artificial seawater and 3.0% (w/v) NaCl solution
      was studied as a function of available chlorine (AC) concentration. The amount of
      AC generated during the DC electric treatment increased in proportion to the
      amount of passed DC. The survival fraction of V. parahaemolyticus cells decreased
      depending on AC concentration. When the generated AC components were completely
      reduced in the presence of sufficient sodium thiosulfate, no inactivation of V.
      parahaemolyticus in the NaCl solution was observed during the DC electric
      treatment. Based on the AC concentration, the inactivation efficacies of the DC
      electric treatment of the seawater and NaCl solution were approximately 4-fold
      and 30-fold that of the exogenous addition of sodium hypochlorite, respectively.
      Fluorometric analysis using 2-[6-(4'-hydroxy)phenoxy-3H-xanthen-3-on-9-yl]benzoic
      acid showed that the generation of highly reactive radical species such as
      hydroxyl radical in the seawater and NaCl solution occurred during the DC
      electric treatment. The amount of generated radical species depended on the
      amount of passed DC. It is concluded that pulsed low-DC electric treatment of
      saline solutions exerts superior inactivation efficacy against V.
      parahaemolyticus to sodium hypochlorite owing to the generation of radical
      species.

PMID- 17189176
TI  - Lactate and ethanol productions by Rhizopus oryzae ATCC 9363 and activities of
      related pyruvate branch point enzymes.
AB  - In Rhizopus oryzae cultivations, lactate production decreased and ethanol and
      biomass productions increased as inoculated spore concentration increased. Spore
      concentrations of 1 x 10(3) and 1 x 10(4) spores ml(-1) induced tightly packed
      clumps, whereas 1 x 10(5) and 1 x 10(6) spores ml(-1) induced filamentous growth.

PMID- 17189178
TI  - Identification of genes from Aspergillus oryzae that are preferentially expressed
      in membrane-surface liquid culture.
AB  - We identified 22 genes from Aspergillus oryzae that are preferentially expressed
      in membrane-surface liquid culture (MSLC), among which Ser/Thr protein kinase
      (aopk1) and phosphatase (aoppt) genes were cloned. We also revealed that aopk1
      encodes a protein with an N-terminal sequence 150 amino acid residues longer than
      that predicted from the registered sequence in GenBank.

PMID- 17189177
TI  - Ex vivo expansion of human cord blood hematopoietic progenitor cells using
      glutaraldehyde-fixed human bone marrow stromal cells.
AB  - Human stromal cells were immortalized and fixed with glutaraldehyde to support an
      ex vivo expansion of human cord blood hematopoietic progenitor cells. In
      addition, this enabled glutaraldehyde-fixed stromal cells to be stored at 4
      degrees C. Although freeze-dried glutaraldehyde-fixed stromal cells did not
      increase the number of the progenitor cells, the percent decrease in the number
      of CD34(+) cells in the presence of freeze-dried glutaraldehyde-fixed stromal
      cells was less than that in the absence of the stromal cells. Thus,
      glutaraldehyde-fixed stromal cells can serve as a stabilizing device for
      hematopoietic cell expansion.

PMID- 17189179
TI  - Pretreatment of polyamide monofilament with hydrochloric acid improves
      sensitivity of three-dimensional microarray, Bio-Strand.
AB  - A single-nucleotide-polymorphism-typing method using a novel three-dimensional
      DNA microarray, Bio-Strand, is promising because it is rapid, inexpensive and
      easily automated. It has been developed with the intent to overcome the drawbacks
      of conventional DNA microarrays, which use flat surfaces and impermeable
      materials such as glass slides; Bio-Strand as a novel DNA microarray, with its
      permeability, has a significantly improved stability compared with conventional
      DNA microarrays that use impermeable materials. In this study, we have developed
      a simple method of pretreating a polyamide monofilament to increase its surface
      area and to make it permeable, which makes Bio-Strand more sensitive and stable,
      allowing it to be adapted for clinical diagnostic applications. The fluorescence
      signal obtained with a nylon 6 monofilament pretreated under optimal conditions
      (hydrolysis by 5 M HCl/ethanol followed by washing with 50% ethanol and 100%
      ethanol) was significantly stronger than that obtained with an untreated
      monofilament.

PMID- 17189180
TI  - Novel in vitro screening system for monoclonal antibodies using hypermutating
      chicken B cell library.
AB  - Here, we report an in vitro screening system for monoclonal antibodies using a
      hypermutating chicken B cell line, DT40-SW. When switching on hypermutation,
      cultured DT40-SW cells constituted an antibody library, from which clones
      secreting antibodies to a test antigen were successfully isolated, and
      genetically stabilized by switching off the mutation machinery.

PMID- 17189181
TI  - 16S rRNA gene-based analysis of microbial community by whole-genome amplification
      and minigel-single-strand conformation polymorphism technique.
AB  - We have developed an analytical technique for the 16S rRNA gene that comprises
      whole-genome amplification and the polymerase chain reaction (PCR)-minigel-single
      strand conformation polymorphism technique (WGA-SSCP). Under optimal conditions,
      SSCP bands could be detected when genomic DNA from bacteria of interest comprised
      0.5% or more of the specimen. This method will be effective for the
      identification of nonculturable bacteria in a microbial community.

PMID- 17189182
TI  - To die or not to die: a HAT trick.
AB  - In this issue of Molecular Cell, two manuscripts (Sykes et al., 2006) propose
      that the decision to undergo apoptosis upon DNA damage is mediated through
      acetylation of p53 within its DNA-binding domain by MYST histone
      acetyltransferases.

PMID- 17189183
TI  - DNA damage signaling recruits the RNA polymerase II binding protein Che-1 to the
      p53 promoter.
AB  - New work by Bruno et al. (2006) describes a mechanistic switch of the
      proliferation-promoting Che-1 activator of E2F-target genes into a cell-cycle
      inhibitor in response to DNA damage, through Che-1 relocalization to, and
      activation of, the p53 tumor suppressor gene.

PMID- 17189184
TI  - SNIP1: Myc's new helper in transcriptional activation.
AB  - c-Myc regulates target genes by engaging a number of transcriptional cofactors.
      In a recent issue of Molecular Cell, Fujii et al. (2006) showed that the FHA
      domain protein SNIP1 is an important c-Myc coactivator that regulates c-Myc
      stability and is overexpressed in many tumors.

PMID- 17189185
TI  - Initiation and beyond: multiple functions of the human mitochondrial
      transcription machinery.
AB  - Mitochondria contain their own DNA (mtDNA) that is expressed and replicated by
      nucleus-encoded factors imported into the organelle. Recently, the core human
      mitochondrial transcription machinery has been defined, comprising a
      bacteriophage-related mtRNA polymerase (POLRMT), an HMG-box transcription factor
      (h-mtTFA), and two transcription factors (h-mtTFB1 and h-mtTFB2) that also serve
      as rRNA methyltransferases. Here, we describe these transcription components as
      well as recent insights into the mechanism of human mitochondrial transcription
      initiation and its regulation. We also discuss novel roles for the mitochondrial
      transcription machinery beyond transcription initiation, including priming of
      mtDNA replication, packaging of mtDNA, coordination of ribosome biogenesis, and
      coupling of transcription to translation.

PMID- 17189186
TI  - Tip60-dependent acetylation of p53 modulates the decision between cell-cycle
      arrest and apoptosis.
AB  - Upon DNA damage and other types of stress, p53 induces either cell-cycle arrest
      or apoptosis depending on the cellular context. However, the molecular mechanisms
      that govern the choice between cell-cycle arrest and apoptosis are not well
      understood. Here, we show that Tip60 is required for both cell growth arrest and
      apoptosis mediated by p53 and also induces its acetylation specifically at lysine
      120 (K120) within the DNA-binding domain. Interestingly, this modification is
      crucial for p53-dependent apoptosis but is dispensable for its mediated growth
      arrest. K120 is a recurrent site for p53 mutation in human cancer, and the
      corresponding acetylation-defective tumor mutant (K120R) abrogates p53-mediated
      apoptosis, but not growth arrest. Thus, our study demonstrates that Tip60
      dependent acetylation of p53 at K120 modulates the decision between cell-cycle
      arrest and apoptosis, and it reveals that the DNA-binding core domain is an
      important target for p53 regulation by posttranslational modifications.

PMID- 17189187
TI  - Acetylation of the p53 DNA-binding domain regulates apoptosis induction.
AB  - The ability of p53 to induce apoptosis plays an important role in tumor
      suppression. Here, we describe a previously unknown posttranslational
      modification of the DNA-binding domain of p53. This modification, acetylation of
      lysine 120 (K120), occurs rapidly after DNA damage and is catalyzed by the MYST
      family acetyltransferases hMOF and TIP60. Mutation of K120 to arginine, as occurs
      in human cancer, debilitates K120 acetylation and diminishes p53-mediated
      apoptosis without affecting cell-cycle arrest. The K120R mutation selectively
      blocks the transcription of proapoptotic target genes such as BAX and PUMA while
      the nonapoptotic targets p21 and hMDM2 remain unaffected. Consistent with this,
      depletion of hMOF and/or TIP60 inhibits the ability of p53 to activate BAX and
      PUMA transcription. Furthermore, the acetyllysine 120 (acetyl-K120) form of p53
      specifically accumulates at proapoptotic target genes. These data suggest that
      K120 acetylation may help distinguish the cell-cycle arrest and apoptotic
      functions of p53.

PMID- 17189188
TI  - Phenotypic consequences of promoter-mediated transcriptional noise.
AB  - A more complete understanding of the causes and effects of cell-cell variability
      in gene expression is needed to elucidate whether the resulting phenotypes are
      disadvantageous or confer some adaptive advantage. Here we show that increased
      variability in gene expression, affected by the sequence of the TATA box, can be
      beneficial after an acute change in environmental conditions. We rationally
      introduce mutations within the TATA region of an engineered Saccharomyces
      cerevisiae GAL1 promoter and measure promoter responses that can be characterized
      as being either highly variable and rapid or steady and slow. We computationally
      illustrate how a stable transcription scaffold can result in "bursts" of gene
      expression, enabling rapid individual cell responses in the transient and
      increased cell-cell variability at steady state. We experimentally verify
      computational predictions that the rapid response and increased cell-cell
      variability enabled by TATA-containing promoters confer a clear benefit in the
      face of an acute environmental stress.

PMID- 17189189
TI  - ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and
      viral genome maintenance.
AB  - Autonomously replicating DNA viruses must evade mitotic checkpoints and actively
      partition their genomes to maintain persistent infection. The E2 protein serves
      these functions by tethering papillomavirus episomes to mitotic chromosomes;
      however, the mechanism remains unresolved. We show that E2 binds ChlR1, a DNA
      helicase that plays a role in sister chromatid cohesion. The E2 mutation W130R
      fails to bind ChlR1 and correspondingly does not associate with mitotic
      chromosomes. Viral genomes encoding this E2 mutation are not episomally
      maintained in cell culture. Notably, E2 W130R binds Brd4, which reportedly acts
      as a mitotic tether, indicating this interaction is insufficient for E2
      association with mitotic chromosomes. RNAi-induced depletion of ChlR1
      significantly reduced E2 localization to mitotic chromosomes. These studies
      provide compelling evidence that ChlR1 association is required for loading the
      papillomavirus E2 protein onto mitotic chromosomes and represents a kinetochore
      independent mechanism for viral genome maintenance and segregation.

PMID- 17189190
TI  - Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that
      ablates HPV chromosomal association.
AB  - Many DNA viruses that are latent in dividing cells are noncovalent passengers on
      mitotic chromosomes and require specific viral-encoded and cellular factors for
      this activity. The chromosomal protein Brd4 is implicated in the hitchhiking of
      bovine papillomavirus-1 (BPV-1), and the viral protein E2 binds to both plasmids
      and Brd4. Here, we present the X-ray crystal structure of the carboxy-terminal
      domain of Brd4 in complex with HPV-16 E2, and with this information have
      developed a Brd4-Tat fusion protein that is efficiently taken up by different
      transformed cells harboring HPV plasmids. In cells treated with these fusion
      proteins for only 2 hr and arrested in metaphase, the HPV DNA, either HPV-16 or 
      31, is displaced from mitotic chromosomes. Mutant Brd4 peptides are deficient in
      ablating this association. We suggest that such peptides may lead to the
      development of inhibitors of latency for many, if not all, papillomaviruses.

PMID- 17189191
TI  - The checkpoint clamp activates Mec1 kinase during initiation of the DNA damage
      checkpoint.
AB  - Yeast Mec1/Ddc2 protein kinase, the ortholog of human ATR/ATRIP, plays a central
      role in the DNA damage checkpoint. The PCNA-like clamp Rad17/Mec3/Ddc1 (the 9-1-1
      complex in human) and its loader Rad24-RFC are also essential components of this
      signal transduction pathway. Here we have studied the role of the clamp in
      regulating Mec1, and we delineate how the signal generated by DNA lesions is
      transduced to the Rad53 effector kinase. The checkpoint clamp greatly activates
      the kinase activity of Mec1, but only if the clamp is appropriately loaded upon
      partial duplex DNA. Activated Mec1 phosphorylates the Ddc1 and Mec3 subunits of
      the clamp, the Rad24 subunit of the loader, and the Rpa1 and Rpa2 subunits of
      RPA. Phosphorylation of Rad53, and of human PHAS-1, a nonspecific target, also
      requires a properly loaded clamp. Phosphorylation and binding studies with
      individual clamp subunits indicate that the Ddc1 subunit mediates the functional
      interactions with Mec1.

PMID- 17189192
TI  - Differential recruitment of the splicing machinery during transcription predicts
      genome-wide patterns of mRNA splicing.
AB  - The splicing machinery associates with genes to facilitate efficient
      cotranscriptional mRNA processing. We have mapped these associations by genome
      localization analysis to ascertain how splicing is achieved and regulated on a
      system-wide scale. Our data show that factors important for intron recognition
      sample nascent mRNAs and are retained specifically at intron-containing genes via
      RNA-dependent interactions. Spliceosome assembly proceeds cotranscriptionally but
      completes posttranscriptionally in most cases. Some intron-containing genes were
      not bound by the spliceosome, including several developmentally regulated genes.
      On this basis, we predicted and verified regulated splicing and observed a role
      for nuclear mRNA surveillance in monitoring those events. Finally, we present
      evidence that cotranscriptional processing events determine the recruitment of
      specific mRNA export factors. Broadly, our results provide mechanistic insights
      into the coordinated regulation of transcription, mRNA processing, and nuclear
      export in executing complex gene expression programs.

PMID- 17189193
TI  - A genome-wide analysis indicates that yeast pre-mRNA splicing is predominantly
      posttranscriptional.
AB  - Recent ChIP experiments indicate that spliceosome assembly and splicing can occur
      cotranscriptionally in S. cerevisiae. However, only a few genes have been
      examined, and all have long second exons. To extend these studies, we analyzed
      intron-containing genes with different second exon lengths by using ChIP as well
      as whole-genome tiling arrays (ChIP-CHIP). The data indicate that U1 snRNP
      recruitment is independent of exon length. Recursive splicing constructs, which
      uncouple U1 recruitment from transcription, suggest that cotranscriptional U1
      recruitment contributes to optimal splicing efficiency. In contrast, U2 snRNP
      recruitment, as well as cotranscriptional splicing, is deficient on short second
      exon genes. We estimate that > or =90% of endogenous yeast splicing is
      posttranscriptional, consistent with an analysis of posttranscriptional snRNP
      associated pre-mRNA.

PMID- 17189195
TI  - Identification of a rapid mammalian deadenylation-dependent decay pathway and its
      inhibition by a viral RNA element.
AB  - Cellular RNAs are subject to quality-control pathways that insure the fidelity of
      gene expression. We previously identified a 79 nt element, the ENE, that is
      essential for the nuclear accumulation of a viral polyadenylated nuclear (PAN)
      RNA. Here, we show that intron-less polyadenylated transcripts such as PAN RNA
      and beta-globin cRNA exhibit two-component exponential decay kinetics in which
      some transcripts are rapidly degraded (t(1/2) = approximately 15 min) while
      others decay more slowly (t(1/2) = approximately 3 hr). Inclusion of the ENE
      protects such transcripts from rapid decay in a poly(A)-dependent fashion. The
      ENE inhibits deadenylation and decay in nuclear extract and prevents
      deadenylation of naked RNA by a purified deadenylase, likely through snoRNA-like
      intramolecular hybridization with the poly(A) tail. The ENE causes increased
      accumulation of splicing-defective beta-globin pre-mRNAs in vivo. We propose that
      the ENE-controlled rapid-decay mechanism for polyadenylated transcripts comprises
      a nuclear pre-mRNA surveillance system in mammalian cells.

PMID- 17189196
TI  - SV40 VP2 and VP3 insertion into ER membranes is controlled by the capsid protein
      VP1: implications for DNA translocation out of the ER.
AB  - Nonenveloped viruses such as Simian Virus 40 (SV40) exploit established cellular
      pathways for internalization and transport to their site of penetration. By
      analyzing mutant SV40 genomes that do not express VP2 or VP3, we found that these
      structural proteins perform essential functions that are regulated by VP1. VP2
      significantly enhanced SV40 particle association with the host cell, while VP3
      functioned downstream. VP2 and VP3 both integrated posttranslationally into the
      endoplasmic reticulum (ER) membrane. Association with VP1 pentamers prevented
      their ER membrane integration, indicating that VP1 controls the function of VP2
      and VP3 by directing their localization between the particle and the ER membrane.
      These findings suggest a model in which VP2 aids in cell binding. After capsid
      disassembly within the ER lumen, VP3, and perhaps VP2, oligomerizes and
      integrates into the ER membrane, potentially creating a viroporin that aids in
      viral DNA transport out of the ER.

PMID- 17189194
TI  - Reverse translocation of tRNA in the ribosome.
AB  - A widely held view is that directional movement of tRNA in the ribosome is
      determined by an intrinsic mechanism and driven thermodynamically by
      transpeptidation. Here, we show that, in certain ribosomal complexes, the
      pretranslocation (PRE) state is thermodynamically favored over the
      posttranslocation (POST) state. Spontaneous and efficient conversion from the
      POST to PRE state is observed when EF-G is depleted from ribosomes in the POST
      state or when tRNA is added to the E site of ribosomes containing P-site tRNA. In
      the latter assay, the rate of tRNA movement is increased by streptomycin and
      neomycin, decreased by tetracycline, and not affected by the acylation state of
      the tRNA. In one case, we provide evidence that complex conversion occurs by
      reverse translocation (i.e., direct movement of the tRNAs from the E and P sites
      to the P and A sites, respectively). These findings have important implications
      for the energetics of translocation.

PMID- 17189197
TI  - Structural basis for protein recognition by B30.2/SPRY domains.
AB  - B30.2/SPRY domains are found in numerous proteins that cover a wide spectrum of
      biological functions, including regulation of cytokine signaling and innate
      retroviral restriction. Herein, we report the crystal structure of the B30.2/SPRY
      domain of a SPRY domain-containing SOCS box (SSB) protein, GUSTAVUS, complexed
      with a 20 amino acid peptide derived from the RNA helicase VASA, revealing how
      these domains recognize target proteins. The peptide-binding site is
      conformationally rigid and has a preformed pocket. The interaction between the
      pocket and the Asp-Ile-Asn-Asn-Asn-Asn sequence within the peptide accounts for
      the high-affinity binding between GUSTAVUS and VASA. This observation led to a
      facile identification of the Glu-Leu-Asn-Asn-Asn-Leu sequence as the recognition
      motif in a proapoptotic protein Par-4 for its interaction with a GUSTAVUS
      homolog, SSB-1. Ensuing analyses indicated that many B30.2/SPRY domains have a
      similar preformed pocket, which would allow them to bind multiple targets.

PMID- 17189198
TI  - Cooperation of multiple chaperones required for the assembly of mammalian 20S
      proteasomes.
AB  - The 20S proteasome is a catalytic core of the 26S proteasome, a central enzyme in
      the degradation of ubiquitin-conjugated proteins. It is composed of 14 distinct
      gene products that form four stacked rings of seven subunits each, alpha(1
      7)beta(1-7)beta(1-7)alpha(1-7). It is reported that the biogenesis of mammalian
      20S proteasomes is assisted by proteasome-specific chaperones, named PAC1, PAC2,
      and hUmp1, but the details are still unknown. Here, we report the identification
      of a chaperone, designated PAC3, as a component of alpha rings. Although it can
      intrinsically bind directly to both alpha and beta subunits, PAC3 dissociates
      before the formation of half-proteasomes, a process coupled with the recruitment
      of beta subunits and hUmp1. Knockdown of PAC3 impaired alpha ring formation.
      Further, PAC1/2/3 triple knockdown resulted in the accumulation of disorganized
      half-proteasomes that are incompetent for dimerization. Our results describe a
      cooperative system of multiple chaperones involved in the correct assembly of
      mammalian 20S proteasomes.

PMID- 17189199
TI  - The "domino theory" of hunger: the hypothalamus is hot.
AB  - Mechanisms by which the hypothalamus senses nutritional status are important for
      many metabolic diseases, including obesity and diabetes. Now, report that
      hypothalamic neurons sense nutritional deficit through a cascade of events
      involving leptin, corticosterone, and glial production of thyroid hormone,
      leading to neuronal induction of uncoupling protein.

PMID- 17189200
TI  - TOR regulation: sorting out the answers.
AB  - Components involved in vesicle trafficking processes such as secretion,
      endocytosis, and autophagy are gaining recognition as important regulators and
      effectors of target of rapamycin (TOR) signaling. A recent report by now
      implicates Pmr1, a secretory pathway Ca(2+)/Mn(2+) ATPase located in the Golgi
      apparatus, as a novel regulator of TOR and its downstream targets in yeast.

PMID- 17189201
TI  - When is a heme transporter not a heme transporter? When it's a folate
      transporter.
AB  - Essential nutrients enter the body through a variety of specific transporter
      molecules expressed in the intestinal epithelium. A recent paper by elegantly
      demonstrates that one of these transporters, previously thought to carry heme, is
      in fact an important folate transporter.

PMID- 17189202
TI  - Angiotensin in the kidney: a key to understanding hypertension?
AB  - A crosstransplantation study between genetically matched angiotensin AT1 receptor
      knockout and wild-type mice revealed that renal AT1 receptors are required for
      the development of angiotensin II-induced hypertension (). However, in this
      experimental setting, hypertension-related left ventricular hypertrophy seemed to
      depend on blood pressure elevation rather than on the expression of AT1 receptors
      in the heart.

PMID- 17189203
TI  - The human cytochrome c oxidase assembly factors SCO1 and SCO2 have regulatory
      roles in the maintenance of cellular copper homeostasis.
AB  - Human SCO1 and SCO2 are metallochaperones that are essential for the assembly of
      the catalytic core of cytochrome c oxidase (COX). Here we show that they have
      additional, unexpected roles in cellular copper homeostasis. Mutations in either
      SCO result in a cellular copper deficiency that is both tissue and allele
      specific. This phenotype can be dissociated from the defects in COX assembly and
      is suppressed by overexpression of SCO2, but not SCO1. Overexpression of a SCO1
      mutant in control cells in which wild-type SCO1 levels were reduced by shRNA
      recapitulates the copper-deficiency phenotype in SCO1 patient cells. The copper
      deficiency phenotype reflects not a change in high-affinity copper uptake but
      rather a proportional increase in copper efflux. These results suggest a
      mitochondrial pathway for the regulation of cellular copper content that involves
      signaling through SCO1 and SCO2, perhaps by their thiol redox or metal-binding
      state.

PMID- 17189205
TI  - The transcriptional coactivator PGC-1beta drives the formation of oxidative type
      IIX fibers in skeletal muscle.
AB  - Skeletal muscle must perform different kinds of work, and distinct fiber types
      have evolved to accommodate these. Previous work had shown that the
      transcriptional coactivator PGC-1alpha drives the formation of type I and IIA
      muscle fibers, which are "slow-twitch" and highly oxidative. We show here that
      transgenic expression of PGC-1beta, a coactivator functionally similar to but
      distinct from PGC-1alpha, causes a marked induction of IIX fibers, which are
      oxidative but have "fast-twitch" biophysical properties. PGC-1beta coactivates
      the MEF2 family of transcription factors to stimulate the type IIX myosin heavy
      chain (MHC) promoter. PGC-1beta transgenic muscle fibers are rich in mitochondria
      and are highly oxidative, at least in part due to coactivation by PGC-1beta of
      ERRalpha and PPARalpha. Consequently, these transgenic animals can run for longer
      and at higher work loads than wild-type animals. Together, these data indicate
      that PGC-1beta drives the formation of highly oxidative fibers containing type
      IIX MHC.

PMID- 17189204
TI  - A central thermogenic-like mechanism in feeding regulation: an interplay between
      arcuate nucleus T3 and UCP2.
AB  - The active thyroid hormone, triiodothyronine (T3), regulates mitochondrial
      uncoupling protein activity and related thermogenesis in peripheral tissues. Type
      2 deiodinase (DII), an enzyme that catalyzes active thyroid hormone production,
      and mitochondrial uncoupling protein 2 (UCP2) are also present in the
      hypothalamic arcuate nucleus, where their interaction and physiological
      significance have not been explored. Here, we report that DII-producing glial
      cells are in direct apposition to neurons coexpressing neuropeptide Y (NPY),
      agouti-related protein (AgRP), and UCP2. Fasting increased DII activity and local
      thyroid hormone production in the arcuate nucleus in parallel with increased GDP
      regulated UCP2-dependent mitochondrial uncoupling. Fasting-induced T3-mediated
      UCP2 activation resulted in mitochondrial proliferation in NPY/AgRP neurons, an
      event that was critical for increased excitability of these orexigenic neurons
      and consequent rebound feeding following food deprivation. These results reveal a
      physiological role for a thyroid-hormone-regulated mitochondrial uncoupling in
      hypothalamic neuronal networks.

PMID- 17189206
TI  - Dissecting multiple steps of GLUT4 trafficking and identifying the sites of
      insulin action.
AB  - Insulin-stimulated GLUT4 translocation is central to glucose homeostasis.
      Functional assays to distinguish individual steps in the GLUT4 translocation
      process are lacking, thus limiting progress toward elucidation of the underlying
      molecular mechanism. Here we have developed a robust method, which relies on
      dynamic tracking of single GLUT4 storage vesicles (GSVs) in real time, for
      dissecting and systematically analyzing the docking, priming, and fusion steps of
      GSVs with the cell surface in vivo. Using this method, we have shown that the
      preparation of GSVs for fusion competence after docking at the surface is a key
      step regulated by insulin, whereas the docking step is regulated by PI3K and its
      downstream effector, the Rab GAP AS160. These data show that Akt-dependent
      phosphorylation of AS160 is not the major regulated step in GLUT4 trafficking,
      implicating alternative Akt substrates or alternative signaling pathways
      downstream of GSV docking at the cell surface as the major regulatory node.

PMID- 17189207
TI  - Gapex-5, a Rab31 guanine nucleotide exchange factor that regulates Glut4
      trafficking in adipocytes.
AB  - Insulin stimulates glucose uptake by promoting translocation of the Glut4 glucose
      transporter from intracellular storage compartments to the plasma membrane. In
      the absence of insulin, Glut4 is retained intracellularly; the mechanism
      underlying this process remains uncertain. Using the TC10-interacting protein
      CIP4 as bait in a yeast two-hybrid screen, we cloned a RasGAP and VPS9 domain
      containing protein, Gapex-5/RME-6. The VPS9 domain is a guanine nucleotide
      exchange factor for Rab31, a Rab5 subfamily GTPase implicated in trans-Golgi
      network (TGN)-to-endosome trafficking. Overexpression of Rab31 blocks insulin
      stimulated Glut4 translocation, whereas knockdown of Rab31 potentiates insulin
      stimulated Glut4 translocation and glucose uptake. Gapex-5 is predominantly
      cytosolic in untreated cells; its overexpression promotes intracellular retention
      of Glut4 in adipocytes. Insulin recruits the CIP4/Gapex-5 complex to the plasma
      membrane, thus reducing Rab31 activity and permitting Glut4 vesicles to
      translocate to the cell surface, where Glut4 docks and fuses to transport glucose
      into the cell.

PMID- 17189208
TI  - Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the
      livers of mice.
AB  - Liver X receptors (LXRs) are nuclear receptors that play crucial roles in lipid
      metabolism in vivo and are activated by oxysterol ligands in vitro. The identity
      of the ligand that activates LXRs in vivo is uncertain. Here we provide two lines
      of evidence that oxysterols are LXR ligands in vitro and in vivo. First,
      overexpression of an oxysterol catabolic enzyme, cholesterol sulfotransferase,
      inactivates LXR signaling in several cultured mammalian cell lines but does not
      alter receptor response to the nonsterol agonist T0901317. Adenovirus-mediated
      expression of the enzyme in mice prevents dietary induction of hepatic LXR target
      genes by cholesterol but not by T0901317. Second, triple-knockout mice deficient
      in the biosynthesis of three oxysterol ligands of LXRs, 24S-hydroxycholesterol,
      25-hydroxycholesterol, and 27-hydroxycholesterol, respond to dietary T0901317 by
      inducing LXR target genes in liver but show impaired responses to dietary
      cholesterol. We conclude that oxysterols are in vivo ligands for LXR.

PMID- 17189218
TI  - Polymorphisms in vitamin K-dependent gamma-carboxylation-related genes influence
      interindividual variability in plasma protein C and protein S activities in the
      general population.
AB  - gamma-Glutamyl carboxylation, a reaction essential for the activity of vitamin K
      dependent proteins, requires the concerted actions of gamma-glutamyl carboxylase
      (GGCX), vitamin K 2, 3-epoxide reductase complex 1 (VKORC1), and the chaperone
      calumenin (CALU). We evaluated the contribution of genetic polymorphisms in
      VKORC1, GGCX, and CALU to interindividual variation in the activities of plasma
      protein C and protein S. We sequenced these 3 genes in 96 Japanese individuals
      and geno-typed 9 representative single-nucleotide polymorphisms in 3655 Japanese
      individuals representative of the general population. The mean activity of
      protein C in women bearing the GG genotype of GGCX 8016G>A (130.8% +/- 1.5%, n =
      156) was significantly greater (P = .002) than that of individuals with either
      the AG (126.8% +/- 0.7%, n = 728) or the AA (125.4% +/- 0.6%, n = 881) genotype,
      after adjusting for confounding factors. The GGCX 8016G>A change leads to the
      substitution of Gin for Arg at amino acid residue 325 (Arg 325 Gln). This effect
      was comparable to that of a previously defined polymorphism in the protein C
      promoter. Mean protein S activity was influenced by the VKORC1 3730G>A and CALU
      20943T>A genotypes, after adjusting for confounding factors. Thus, polymorphisms
      in genes involved in the vitamin K-dependent gamma-carboxylation reaction
      influence interindividual variation in the activities of protein C and protein S
      in the general population.

PMID- 17189219
TI  - Plasminogen activator inhibitor 1 promotes a poor prognosis in sepsis-induced
      disseminated intravascular coagulation.
AB  - Sepsis-induced disseminated intravascular coagulation (DIC) is a serious
      condition because it is closely linked to the development of multiple organ
      dysfunctions. We compared molecular fibrinolysis markers for 117 patients with
      sepsis-induced DIC and 1627 patients with nonseptic DIC. Levels of fibrinogen and
      fibrin degradation products and D-dimer were significantly lower in sepsis
      induced DIC cases than in nonseptic DIC cases. In septic DIC cases, plasma
      plasminogen activator inhibitor 1 (PAI-1) levels were significantly higher than
      in nonseptic DIC cases. D-dimer levels were negatively correlated with plasma PAI
      1 levels in septic DIC cases. Multiple Organ Dysfunction Scores were
      significantly higher in septic DIC patients with PAI-1 levels >90 ng/mL than in
      the group with PAI-1 levels <30 ng/mL. The Kaplan-Meier survival functions until
      28 days after DIC diagnosis were significantly lower in the group with PAI-1
      levels >90 ng/mL than in the other groups. In a multivariate analysis, plasma PAI
      1 levels at DIC diagnosis were an independent risk factor for mortality in sepsis
      induced DIC (hazard ratio, 1.012; P = .008). These data suggest that plasma PAI-1
      plays an important role in sustaining DIC in septic DIC cases and contributes to
      multiple organ failure and decreased survival in such patients.

PMID- 17189220
TI  - Lung injury associated with bortezomib therapy in relapsed/refractory multiple
      myeloma in Japan: a questionnaire-based report from the "lung injury by
      bortezomib" joint committee of the Japanese society of hematology and the
      Japanese society of clinical hematology.
AB  - Bortezomib is a proteasome inhibitor that can be effective in the treatment of
      refractory and relapsed multiple myeloma. Recently, severe pulmonary
      complications associated with bortezomib therapy have been reported in Japan.
      Because bortezomib has not yet been approved for general use in Japan and is
      imported by attending physicians on the request of patients, The Japanese Society
      of Hematology and The Japanese Society of Clinical Hematology sent urgent
      questionnaires to the councilors of both societies to explore the situation and
      the details of pulmonary complications associated with bortezomib therapy.
      Clinical details were available for 46 patients who had been treated with
      personally imported bortezomib in Japan. Seven patients (15.2%), including 3 who
      died from respiratory failure, showed complications definitely or probably caused
      by bortezomib. Of the 7 patients, 6 had a prior history of stem cell
      transplantation (SCT), whereas only 14 of 39 patients without lung injury had
      received SCT treatment (P = .033, Fisher exact test). Multivariate analysis
      revealed that the concomitant use of corticosteroids might reduce the risk of
      lung injury (P = .024; odds ratio, 0.055) and that a previous SCT might increase
      the risk (P = .042; odds ratio, 13.140). We summarized these data from
      questionnaires for a limited Japanese cohort and therefore do not know the
      precise incidence of lung injury linked to fatal progression. Thus, future
      verification concerning this matter is warranted after the approval of bortezomib
      for use in Japan. Clinicians should be aware of the possibility of severe
      pulmonary complications associated with bortezomib therapy.

PMID- 17189222
TI  - Acute myelomonocytic leukemia with dysplastic bone marrow eosinophils showing
      t(5;17)(q13;q11) and a secondary chromosomal aberration, inv(16)(p13q22).
AB  - inv(16)(p13q22) is associated with de novo acute myelomonocytic leukemia with
      dysplastic bone marrow eosinophils (AMML Eo), which has a relatively favorable
      clinical course with a longer remission duration and better survival prospects.
      On the other hand, t(5; 17)(q13;q11), although relatively rare, has been reported
      to be a component of complex chromosomal abnormalities in myelodysplastic
      syndromes and secondary acute myeloid leukemia (AML). We treated a 29-year-old
      woman with the first reported case of de novo AMML Eo with inv(16)(p13q22) in
      addition to t(5; 17)(q13;q11). Although she attained complete remission (CR)
      immediately after induction therapy, the disease recurred 1 year after the
      completion of consolidation therapies. She underwent HLA-matched unrelated
      allogeneic bone marrow transplantation (UBMT), together with a myeloablative
      conditioning regimen, after achieving a second CR and has survived without a
      recurrence for more than 24 months since UBMT. In general, certain secondary
      chromosomal abnormalities are associated with the phenotype of the disease, which
      retains its essential biologic characteristics established by the primary
      abnormality. Accordingly, the primary nature of the leukemic cells in this case
      differs from the findings for core-binding factor AML with inv(16)(p13q22). We
      believe this report is the first of de novo AMML Eo with t(5; 17)(q13;q11)
      showing as a secondary chromosomal aberration with inv(16)(p13q22).

PMID- 17189221
TI  - Multiple granulocytic sarcomas in essential thrombocythemia.
AB  - A 59-year-old woman was diagnosed with essential thrombocythemia in 1988 and had
      been treated with hydroxyurea, mitobronitol, busulfan, and ranimustine, in that
      order. Hepatosplenomegaly, low-grade fever, and body weight loss manifested, and
      a few blasts were noted in the peripheral blood studied in March 2002. A biopsied
      specimen of the bone marrow showed myelofibrosis but not a leukemia in August
      2004. An abnormal karyotype with der(1; 13) appeared for the first time. She was
      treated with low-dose prednisolone. In January 2005, she experienced left hip
      joint pain, and magnetic resonance scanning showed a tumoral lesion in the
      femoral head. Histological diagnosis of the biopsied mass revealed that it was a
      granulocytic sarcoma, and radiotherapy was performed. In April 2005, bone
      scintigraphy showed multiple lesions. She became febrile and red blood cell
      transfusion-dependent with hepatosplenomegaly and a small number of circulating
      blasts. Intravenous cytarabine (low dose) and etoposide relieved the fever and
      hepatosplenomegaly; however, she developed a pathologic fracture of the right
      humerus. An additional karyotypic abnormality (7q22 deletion) was noted. She
      subsequently died of infection. Granulocytic sarcoma is very rare in essential
      thrombocythemia, and this patient may be the first reported case of essential
      thrombocythemia that developed multiple lesions and a pathologic fracture without
      transformation to overt leukemia.

PMID- 17189223
TI  - Sacroiliitis as an initial manifestation of acute myelogenous leukemia.
AB  - Sacroiliitis is the most pathognomonic and earliest manifestation of ankylosing
      spondylitis. We herein report a 28-year-old female patient who presented with
      sacroiliitis as an initial manifestation of acute myelogenous leukemia (AML). She
      had a 3-month history of anemia and walking difficulty. Bone marrow findings
      revealed an increase of blasts with trilineage dysplasia. Although she was
      initially diagnosed with myelodysplastic syndrome (MDS), blasts rapidly increased
      and AML developed 1 month after the diagnosis of MDS with Sacroiliitis. Induction
      chemotherapy failed to induce a complete remission of AML, but it did effectively
      treat the sacroiliitis. However, the sacroiliitis relapsed when the leukemia
      cells progressed thereafter. Oral corticosteroids helped ameliorate the
      sacroiliitis. She underwent bone marrow transplantation (BMT) from an HLA
      identical sister during a nonremission period; however, the leukemic cells began
      to rapidly increase from day 30 after BMT. The close relationship between the
      occurrence of sacroiliitis and AML suggested that autoimmune sacroiliitis was a
      paraneoplastic phenomenon of AML in this patient. Although autoimmune disorders
      develop in a substantial number of MDS patients, they are rarely observed in de
      novo AML. No previous report has described sacroiliitis as the initial
      manifestation of de novo AML.

PMID- 17189225
TI  - Human herpesvirus 6 meningoencephalitis in allogeneic hematopoietic stem cell
      transplant recipients.
AB  - We retrospectively investigated the clinical characteristics of human herpesvirus
      6 (HHV-6) meningoencephalitis within 100 days after allogeneic hematopoietic stem
      cell transplantation (HSCT). Of 1148 patients who received transplants between
      January 1999 and December 2003, 11 patients (0.96%) with HHV-6
      meningoencephalitis were identified. Ten of 11 recipients received hematopoietic
      stem cells from donors other than HLA-identical siblings. Confusion was the most
      frequent central nervous system (CNS) symptom, and a skin rash with high-grade
      fever preceded the CNS symptoms in 9 patients. Magnetic resonance imaging of the
      brain showed an abnormal increased T2 signal in the hypothalamus of 5 patients.
      Eight patients were treated with ganciclovir, and an improvement of CNS symptoms
      was obtained in 3 patients; 3 patients treated with acyclovir showed no
      improvement. Improvement in the meningoencephalitis seemed less frequent in
      patients with abnormal findings in the hypothalamus than in those without such
      findings. Because the symptoms of HHV-6 meningoencephalitis mimicked those of
      cyclosporine- or tacrolimus-induced encephalopathy, the drugs were withdrawn at
      the onset of CNS symptoms in 10 patients, resulting in the development of grade
      IV graft-versus-host disease (GVHD) in 5 patients. Three patients died of HHV-6
      meningoencephalitis, and 6 died of other causes, including GVHD. In conclusion,
      HHV-6 meningoencephalitis is a rare but potentially life-threatening complication
      in patients who undergo allogeneic HSCT. Careful assessment of the clinical
      findings and the brain may allow early and precise diagnosis of HHV-6
      meningoencephalitis and contribute to improving its prognosis.

PMID- 17189224
TI  - Usefulness of quantitative assessment of JunB gene expression as a marker for
      monitoring chronic myeloid leukemia patients undergoing imatinib therapy.
AB  - JunB is a component of the activator protein 1 transcription factors and has been
      identified to be important in hematopoiesis. Transgenic mice lacking JunB
      expression develop myeloproliferative disease resembling human chronic myeloid
      leukemia (CML). JunB expression was significantly decreased in CML patients. We
      used real-time quantitative reverse transcription-polymerase chain reaction
      analysis to monitor both JunB and BCR-ABL expression during imatinib therapy.
      Nineteen patients were evaluated every 2 to 4 weeks, and their levels of JunB
      expression before therapy were significantly decreased compared with those of
      healthy individuals. After imatinib therapy, an increase in JunB expression was
      found in 5 patients, all of whom achieved a complete cytogenetic response (CCR)
      and molecular response (MR), with a decrease in BCR-ABL expression. JunB
      expression decreased to a very low level in 2 patients, both of whom showed
      progression to blast crisis. Variable JunB expression was found in the other 12
      patients, and their outcomes were mostly driven by BCR-ABL levels. The patients
      with an increase in JunB expression were statistically more likely to achieve a
      major cytogenetic response (P = .045), CCR (P = .033), and MR (P = .033) than the
      group with no increase in JunB expression, and a durable response was observed.
      This study revealed that an increase in JunB expression is a good prognostic
      marker for predicting clinical response in CML patients treated with imatinib
      when such data are combined with an evaluation of BCR-ABL expression.

PMID- 17189227
TI  - Late relapse of acute myelogenous leukemia followed by epstein-barr virus
      associated lymphoproliferative disease 11 years after allogeneic bone marrow
      transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) following
      myeloablative conditioning represents the treatment of choice for patients with
      chemotherapy-resistant leukemia. We describe a 49-year-old man with advanced,
      refractory acute myelogenous leukemia (AML) that was treated successfully by
      allogeneic bone marrow transplantation from a sibling donor with HLA mismatched
      at 1 locus. However, the patient developed a quiescent form of chronic graft
      versus-host disease (GVHD) 7 years after transplantation, requiring long-term
      immunosuppressive therapy. AML relapse was documented 11 years after
      transplantation. Subsequently, Epstein-Barr virus (EBV)-associated
      posttransplantation lymphoproliferative disorder (PTLD) was also diagnosed.
      Immune reconstitution after allo-HSCT might have been impaired by the persistent
      chronic GVHD and the prolonged administration of immunosuppressive agents. As a
      result, immune surveillance against remaining quiescent leukemic cells as well as
      viral infection may have been defective, leading to the relapse of leukemia and
      EBV-associated PTLD.

PMID- 17189226
TI  - Pancreatic hyperamylasemia and hyperlipasemia in association with cytomegalovirus
      infection following unrelated cord blood transplantation for acute myelogenous
      leukemia.
AB  - Cytomegalovirus (CMV)-associated pancreatitis is rare after allogeneic
      hematopoietic stem cell transplantation (SCT). We describe a patient who
      developed pancreatic hyperamylasemia and hyperlipasemia in association with CMV
      infection after cord blood transplantation (CBT). A 31-year-old man with acute
      myelogenous leukemia underwent CBT. A neutrophil count consistently greater than
      500/microL was achieved on day +21. Positive results for CMV antigenemia on days
      +35 and +67 prompted 2 courses of preemptive therapy with ganciclovir or
      foscarnet. The CMV antigenemia value again became positive on day +134. On day
      +141, serum amylase and lipase activities markedly increased to 1221 IU/L and 894
      IU/L, respectively. The patient had no abdominal symptoms. Ultrasonography and
      computed tomography results showed no abnormalities of the pancreas. A diagnosis
      of possible pancreatitis was made. After the initiation of foscarnet therapy, the
      CMV antigenemia results soon became negative, and serum amylase and lipase
      activities returned to normal. Therefore, CMV infection was considered to play a
      major role in the development of pancreatic hyperamylasemia and hyperlipasemia in
      our patient. The present report indicates that CMV infection should be included
      in the differential diagnosis for patients with pancreatic hyperamylasemia after
      SCT.

PMID- 17189228
TI  - Late-onset fatal Epstein-Barr virus-associated hemophagocytic syndrome following
      cord blood cell transplantation for adult acute lymphoblastic leukemia.
AB  - A 43-year-old Japanese woman underwent unrelated cord blood transplantation (CBT)
      during remission for acute lymphoblastic leukemia with t(4; 11)(q21;q23).
      Tacrolimus was given for prophylaxis of graft-versus-host disease. The
      posttransplantation clinical course was mostly uneventful, and the leukemia
      remained in remission. Fourteen months after CBT, the patient developed
      pancytopenia and hepatic dysfunction with persistent high-grade fever. The bone
      marrow was hypocellular with increased numbers of macrophages and hemophagocytes.
      The numbers of Epstein-Barr virus (EBV) copies in peripheral blood samples were
      remarkably high. Although the patient showed complete donor-type hematopoiesis,
      the titer of viral capsid antigen immunoglobulin G was low, and the results of a
      test for EBV nuclear antigen were negative. There was no clinical response to the
      reduction of immunosuppressive therapy or to the administration of high-dose
      methylprednisolone, human immunoglobulin, or acyclovir. The patient died 466 days
      after CBT of massive gastrointestinal hemorrhage due to bone marrow and hepatic
      failures. This case demonstrates that fatal EBV-associated hemophagocytic
      syndrome (HPS) can occur more than 1 year after CBT. This report is the first of
      a case of late-onset EBV-associated HPS following CBT.

PMID- 17189230
TI  - Pregnancies in patients with chronic myeloid leukemia in the era of imatinib.

PMID- 17189231
TI  - Intensifying daunorubicin in induction for patients with core binding factor
      leukemia.

PMID- 17189229
TI  - Combined use of dendritic cells enhances specific antileukemia immunity by
      leukemia cell-derived heat shock protein 70 in a mouse model with minimal
      residual leukemia cells.
AB  - We have reported that immunotherapy using leukemia cell-derived heat shock
      proteins (HSPs) is effective against minimal residual disease (MRD) after
      syngeneic stem cell transplantation (SCT) in mice. However, leukemia patients
      after SCT are usually immunocompromised and immunologically tolerant to leukemia
      cells. We investigated whether the use of dendritic cells (DCs) in combination
      with HSP70 enhances cytotoxicity against B-cell leukemia cell line A20 in mice
      after syngeneic SCT. All unimmunized mice died of leukemia early after A20 cell
      inoculation, whereas mice immunized with HSP70 or HSP70-pulsed DCs survived
      significantly longer. Although only 60% of the HSP70-immunized mice survived, all
      mice immunized with HSP70-pulsed DCs survived without MRD. In addition, the
      cytotoxicities against A20 cells for splenocytes from mice immunized with HSP70
      pulsed DCs were significantly higher than those of HSP70-immunized mice, and the
      cytotoxicities against A20 cells were significantly blocked by anti-CD8 antibody
      and by major histocompatibility complex class I antibody, but not by anti-CD4
      antibody. Moreover, abnormalities were detected in neither the biochemical data
      nor the histopathologic findings. These findings indicate that the combined use
      of DCs and leukemia cell-derived HSP70 enhances the antileukemia effect by
      inducing the specific cytotoxicities of CD8+ cytotoxic T-cells, thereby
      eradicating MRD effectively and safely, even in an immunocompromised state after
      syngeneic SCT. This approach may thus be useful for further application of HSP in
      leukemia patients after autologous SCT.

PMID- 17189232
TI  - Gelatinous degeneration in a recipient of allogeneic bone marrow transplantation.

PMID- 17189233
TI  - Different kinetics of WT1 and PML-RARalpha gene expression levels during
      remission induction therapy with all-trans retinoic acid alone in acute
      promyelocytic leukemia.

PMID- 17189234
TI  - Rapid bone marrow dissemination after surgery in localized gastric diffuse large
      B-cell lymphoma: a case report.

PMID- 17189235
TI  - Anxiety sensitivity and its impact on pain experiences and conditions: a state of
      the art.
AB  - This paper serves as an introduction to the special issue of Cognitive Behaviour
      Therapy devoted to the topic of anxiety sensitivity (AS) and its impact on pain
      experiences and conditions. We provide a historical overview of relevant
      cognitive behavioural models of chronic pain, summarize recent models
      incorporating the AS construct, and introduce the papers in the special issue.
      These papers are organized into two sets--basic laboratory-based investigations
      and relatively more applied studies. We attempt to highlight some of the most
      important findings from each of these investigations and studies, in turn. Then,
      we consider several important conclusions derived from the set of special issue
      papers and the implications of these for the practice of cognitive-behavioural
      interventions with pain populations. Finally, we make several suggestions for
      directions for future investigations in this burgeoning area of cognitive
      behavioural research and practice.

PMID- 17189236
TI  - Differences in high and low anxiety sensitive women's responses to a laboratory
      based cold pressor task.
AB  - Anxiety sensitivity (AS) has been linked to a variety of disabling chronic health
      conditions, including pain-related conditions. A recent study has found that
      healthy women with high AS reported significantly higher levels of sensory and
      affective pain on an experimental cold pressor task compared to women with low
      AS. However, this study found no differences between AS groups for pain tolerance
      or pain threshold. In the present study, which was designed to replicate and
      extend these findings, 90 undergraduate university women were selected for
      inclusion in 1 of 2 AS groups (high or low) based on their screening scores on a
      16-item measure of AS. Participants were tested individually on a lab-based cold
      pressor task using a variety of self-report and observer-measured variables. Data
      analyses revealed that, as expected, the high AS participants reported
      significantly more fear in response to the cold pressor on a relevant item of the
      McGill Pain Questionnaire-Short Form (SF-MPQ) than did the low AS participants.
      Also as expected, the high AS participants reported more pain in response to the
      cold pressor on the Present Pain Index (PPI) of the SF-MPQ than did the low AS
      participants. High AS participants did not differ from low AS participants on
      other aspects of the cold pressor response (e.g. pain threshold, pain tolerance,
      pain recovery). These results support the role of pain-related fear as a
      mediating variable between AS and increased perceived pain intensity.

PMID- 17189237
TI  - Assessing the relationship between cold pressor pain responses and dimensions of
      the anxiety sensitivity profile in healthy men and women.
AB  - Anxiety sensitivity (AS) has been shown previously to be an important factor in
      the perception and experience of experimentally induced pain within healthy
      adults. The aim of the current study was to extend this research by: (i) using
      the Anxiety Sensitivity Profile (ASP) as an alternative measure of AS; (ii)
      examining whether different coping instructions affect pain reports; and (iii)
      investigating potential differences between men and women. Participants were 50
      healthy adults (23 males, 27 females) who were required to complete 2 versions of
      the cold pressor pain task; one version required the use of control instructions,
      whereas the other made use of acceptance-based instructions. Although the coping
      instructions were found to affect pain thresholds (acceptance resulted in lower
      thresholds), a similar pattern of correlations were found between the pain
      indexes and AS under both conditions. Of the ASP subscales, the gastrointestinal
      and cognitive concerns components were found to be the most strongly related to
      pain experiences. When the analysis was conducted separately for each sex, the
      ASP scales were related to the self-report measures of pain in women, whereas
      they were related to the behavioural measures of pain in men. These results not
      only confirm that AS is associated with experimental pain, but that there may be
      sex differences in this relationship.

PMID- 17189239
TI  - The role of anxiety sensitivity in subjective and physiological responses to
      social and physical stressors.
AB  - This study examined the specificity of the relationship between anxiety
      sensitivity (AS), a measure of catastrophizing about arousal-related sensations,
      and pain responses, by examining the effect of AS on responses to stressors of a
      physical and social nature. Healthy men and women (n = 129) between the ages of
      18 and 25 years were recruited from the community to participate in a study
      examining subjective, cognitive and behavioural responses to different types of
      stressors. Participants were randomly assigned to one of 3 groups: (i) a neutral
      condition in which they sat quietly and read a popular magazine; (ii) a social
      stress condition in which they anticipated having to give a self-disclosing
      speech; and (iii) a physical stress condition in which they were presented with 3
      countdown to shock trials where a mild electrical shock was administered on the
      non-dominant arm. Subjective ratings and physiological responses were recorded in
      anticipation of the stressor and immediately after stress exposure. Results
      indicated that AS was indirectly related to pain ratings via its effect on
      anticipatory anxiety ratings. AS was associated with anticipatory anxiety
      ratings, regardless of whether the stressor was of a physical or social nature.
      Furthermore, AS was not shown to be directly associated with exaggerated
      subjective or physiological reactions to the physical stressor. These results
      indicate that the role of AS in pain responses may be mediated through a global
      effect on anxiety, and limited to the anticipatory stage of the pain experience.
      If future studies yield similar findings in pain patients, then they would
      suggest that interventions for helping individuals high in AS should focus on
      catastrophic thinking in anticipation of stressors in general, rather than on
      pain-specific stressors.

PMID- 17189238
TI  - Relationships among anxious symptomatology, anxiety sensitivity and laboratory
      pain responsivity in children.
AB  - Existing laboratory-based research in adult samples has suggested that anxiety
      sensitivity (AS) increases an individual's propensity to experience pain-related
      anxiety, which in turn enhances pain responsivity. Such relationships have not
      been examined in younger populations. Thus, the present study used structural
      equation modeling (SEM) to test a conceptual model in which AS would evidence an
      indirect relationship with pain intensity via its contribution to state-specific
      anticipatory anxiety in relation to a variety of laboratory pain tasks (cold
      pressor, thermal heat, and pressure pain) in 234 healthy children (116 girls;
      mean age = 12.6 years, range = 8-18 years). The model further hypothesized that
      existing anxious symptomatology would demonstrate a direct relationship with pain
      intensity. Results of the SEM supported the proposed conceptual model with the
      total indirect effect of AS accounting for 29% of the variance in laboratory pain
      intensity via its effects on pain-related anticipatory anxiety. AS did not
      however, evidence a direct relationship with pain intensity. Anxious
      symptomatology on the other hand, demonstrated a significant direct effect on
      pain intensity, accounting for 15% of variance. The combined effects of AS,
      anxiety symptoms, and anticipatory anxiety together explained 62% of the variance
      in pain intensity. These relationships did not differ for boys and girls,
      indicating no moderating effect of sex in the proposed model. The present results
      support the potential benefit of assessing both AS and anxiety symptoms in
      children prior to undergoing painful stimulation.

PMID- 17189240
TI  - Tendency to catastrophize somatic sensations: pain catastrophizing and anxiety
      sensitivity in predicting headache.
AB  - General catastrophic thinking styles about uncomfortable bodily sensations may
      predispose the development of common health pathologies, such as persistent
      headache. The purpose of this research was to explore the relationships between
      the Pain Catastrophizing (PC) Scale and Anxiety Sensitivity (AS) Index, which
      measure tendencies to catastrophize pain- and anxiety-related somatic sensations,
      respectively. A non-clinical sample completed the PC Scale, AS Index, and health
      outcome questionnaires regarding headache (n = 1018). Results revealed that: (i)
      AS and PC are empirically separate constructs; (ii) the overlap between PC and AS
      lies within the domain of fearing physical catastrophe; (iii) AS independently
      predicts weekly headache, headache pain intensity, and the number of a wide range
      of physical symptoms associated with headache; and (iv) PC independently predicts
      the presence of weekly headache. Limitations and implications of this research,
      as well as recommendations for future research directions are discussed.

PMID- 17189241
TI  - Strategic and automatic threat processing in chronic musculoskeletal pain: a
      startle probe investigation.
AB  - Attentional bias research with chronic pain samples has yielded conflicting
      results. In the present investigation the startle paradigm was used to test the
      postulate that fear-based mechanisms play an important role in attentional biases
      for pain-related threat in chronic pain. Participants, including 31 individuals
      with chronic musculoskeletal pain and 20 healthy controls, completed a startle
      task designed to measure attention to different types of words (neutral vs
      sensory pain vs affective pain vs health catastrophe) presented at different
      levels of cognitive processing (strategic vs automatic). Measures of fear-based
      individual difference variables, including anxiety sensitivity and fear of pain,
      were also completed. Startle amplitudes and latencies to acoustic startle probes
      that followed word presentations were recorded. Data were analyzed with repeated
      measures ANOVAs and correlational analysis. Significant between-group differences
      were found indicating that, relative to chronic pain participants, healthy
      controls had higher startle amplitude index scores for health catastrophe words.
      There was also a trend among patients with chronic pain for greater startle
      amplitude index scores for strategic presentations of sensory pain words. In the
      automatic condition, all participants demonstrated a lower startle latency index
      for sensory words relative to both affect and health catastrophe words,
      suggesting participants had more difficulty disengaging from affect and health
      catastrophe words or were more avoidant of sensory words. Correlational analyses
      indicated that startle response indices for words related to health catastrophe
      became more pronounced for chronic pain patients as anxiety sensitivity and fear
      of pain increased. Implications and directions for future research are discussed.

PMID- 17189242
TI  - A brief cognitive-behavioral approach to reducing anxiety sensitivity decreases
      pain-related anxiety.
AB  - Anxiety sensitivity (AS; fear of anxiety-related sensations) is a known risk
      factor for anxiety disorders and recently has been linked to pain disorders. The
      present study was guided by the hypothesis that a program designed to reduce AS
      levels might also result in a decrease in anxiety related to pain sensations.
      Female undergraduates, selected as either high or low in AS according to
      screening scores on the Anxiety Sensitivity Index (ASI), were randomly assigned
      to participate in 3 1-hour, small group sessions of either cognitive behavioral
      therapy (CBT; psycho-education, cognitive restructuring, and interoceptive
      exposure) or a non-specific treatment (NST). Immediately prior to and following
      the intervention, participants completed the 20-item Pain Anxiety Symptoms Scale
      (PASS-20). Consistent with hypothesis, results revealed a 3-way interaction
      between AS group, intervention condition, and time on PASS-20 total scores. Only
      participants with high pre-morbid levels of AS assigned to the CBT condition
      showed a significant reduction in scores on the PASS-20 from pre- to post
      treatment. Implications for improving CBT approaches for pain disorders are
      discussed.

PMID- 17189243
TI  - Acupuncture for fibromyalgia--a systematic review of randomized clinical trials.
AB  - OBJECTIVE: Acupuncture is often used and frequently advocated for the symptomatic
      treatment of fibromyalgia. A systematic review has previously demonstrated
      encouraging findings. As it is now outdated, we wanted to update it. METHODS: We
      searched seven electronic databases for relevant randomized clinical trials
      (RCTs). The data were extracted and validated independently by both authors. As
      no meta-analysis seemed possible, the results were evaluated in narrative form.
      RESULTS: Five RCTs met our inclusion criteria, all of which used acupuncture as
      an adjunct to conventional treatments. Their methodological quality was mixed and
      frequently low. Three RCTs suggested positive but mostly short-lived effects and
      two yielded negative results. There was no significant difference between the
      quality of the negative and the positive RCTs. All positive RCTs used electro
      acupunture. CONCLUSION: The notion that acupuncture is an effective symptomatic
      treatment for fibromyaligia is not supported by the results from rigorous
      clinical trials. On the basis of this evidence, acupuncture cannot be recommended
      for fibromyalgia.

PMID- 17189245
TI  - Is the report of widespread body pain associated with long-term increased
      mortality? Data from the Mini-Finland Health Survey.
AB  - OBJECTIVE: To determine whether an observation in a UK study, that persons with
      chronic widespread pain are at long-term increased risk of cancer mortality, can
      be replicated in a different setting. METHODS: Subjects were participants aged
      >or=30 yrs in the Mini-Finland Health Survey conducted between 1979 and 1980.
      Information collected included prevalent pains at different joints throughout the
      body, demographic, anthropometric, lifestyle and occupational factors. During
      follow-up, until 1994, information on vital status and cause of death was
      obtained. RESULTS: 7182 persons participated (89.8%). The prevalence of
      widespread body pain (pain at four or more sites) was 20% in females and 12% in
      males, and during follow-up there were a total of 1647 deaths. The risk of death
      was not elevated amongst those with widespread pain [relative risk (RR): 0.86;
      95% confidence interval (CI): 0.74-1.00], and in particular, those with
      widespread pain were at a slightly lower risk of several disease-specific causes
      of death and cancer death (RR: 0.64; 95% CI: 0.46-0.91). CONCLUSIONS: This study
      of multiple pains has not confirmed a previous observation of an association
      between the reporting of widespread pain and subsequent increased risk of cancer
      death. Differences in the definitions used or, more probably, the population
      studied, in particular, a larger rural population with more multiple pains
      related to physical activity may account for the differences.

PMID- 17189244
TI  - Repeated B lymphocyte depletion with rituximab in rheumatoid arthritis over 7
      yrs.
AB  - OBJECTIVE: To assess safety and efficacy of repeated B-cell depletion with
      rituximab in patients with rheumatoid arthritis (RA). METHODS: Thirty-seven
      patients with refractory RA entered into a programme of repeated B-lymphocyte
      depletion (up to 5 cycles, 89 cycles in total) with protocols based on the anti
      CD20 monoclonal antibody, rituximab, have been observed over periods of >5 yrs (n
      = 22) or 3-5 yrs (n = 14). RESULTS: Twenty two subjects have been followed up for
      >5 yrs. Average duration of benefit per cycle was 15 months (maximum 43 months),
      and time to re-treatment 20 months. Nineteen patients remain on the programme.
      Patients were withdrawn for lack of efficacy (n = 5), hypersensitivity infusion
      reaction (n = 1), brevity of response (n = 8), or occurrence of adverse
      respiratory events (n = 1). Sixteen major lower respiratory events occurred
      during the 180 patient-yrs of follow-up. Of these only one had low IgG. In
      patients receiving rituximab +/- cyclophosphamide (cy) carcinomata have developed
      as follows: breast (3, +cy), ovary (1, +cy), transitional cell (1, +cy), and
      renal cell (1, -cy). Falls in total immunoglobulin levels to below the normal
      range occurred in 12 patients for IgM (undetectable levels in three after
      repeated cycles), seven for IgG and one for IgA, not taking into account patients
      who started off with low immunoglobulin levels before the first cycle.
      CONCLUSION: Repeated B-lymphocyte depletion over a 5-yr period appears to be an
      acceptable and relatively well-tolerated therapy in RA with a relatively high
      rate of continuation. Long-term effects on immunoglobulin levels require
      surveillance.

PMID- 17189246
TI  - Treatment of vasculitic peripheral neuropathy: a retrospective analysis of
      outcome.
AB  - BACKGROUND: Vasculitis of the peripheral nervous system (PNS) is rare. There are
      no controlled treatment trials, and clinical practice is guided by experience
      from case series and indirectly by analogy with systemic vasculitis. METHODS: We
      identified patients (n=212) with possible vasculitic peripheral neuropathy (VPN)
      from the neuropathology and neurophysiology records of two centres over 28 years.
      Case-notes were available for 181, from which, 106 cases of clinicopathological
      VPN were identified. Adequate treatment data were available in 100; follow-up
      data, in 93. RESULTS: Of 106 cases, 95 had systemic vasculitis and 11 had
      vasculitis confined to the PNS. Pharmacological treatment (94/100 cases) was
      corticosteroid-based, and included cyclophosphamide in 54; 17 received additional
      agents. Initial stabilization was achieved in all but six. One-year survival was
      90.3%. Of the nine who died in the first years (mean age 73 years), seven had
      received cyclophosphamide, and all but two had severe, multisystem vasculitis.
      The neurological relapse rate was 10%. Only one relapse occurred after
      cyclophosphamide treatment. Outcome was reported as good in 72% (78% in those who
      relapsed). DISCUSSION: Death and relapse were infrequent in treated patients.
      Relapse occurred almost exclusively in patients treated with prednisolone alone.
      Aggressive early treatment with cyclophosphamide may prevent relapse. The current
      management approach to VPN appears largely effective, especially if
      cyclophosphamide is used.

PMID- 17189247
TI  - Early neurological deterioration in acute stroke.

PMID- 17189249
TI  - Tel2 is required for activation of the Mrc1-mediated replication checkpoint.
AB  - Proteins belonging to the Tel2/Rad-5/Clk-2 family are conserved among eukaryotes
      and are involved in various cellular processes, such as cell proliferation,
      telomere maintenance, the biological clock, and the DNA damage checkpoint.
      However, the molecular mechanisms underlying the functions of these molecules
      remain largely unclear. Here we report that in the fission yeast,
      Schizosaccharomyces pombe, Tel2 is required for efficient phosphorylation of
      Mrc1, a mediator of DNA replication checkpoint signaling, and for activation of
      Cds1, a replication checkpoint kinase, when DNA replication is blocked by
      hydroxyurea. In fact, Tel2 is required for survival of replication fork arrest
      and for the replication checkpoint in cells lacking Chk1, another checkpoint
      kinase the role of which overlaps that of Cds1 in cell cycle arrest by
      replication block. In addition, Tel2 plays important roles in entry into S phase
      and in genome stability. Tel2 is essential for vegetative cell growth, and the
      tel2Delta strain accumulated cells with 1C DNA content after germination. In the
      absence of hydroxyurea, Tel2 is vital in the mutant lacking Swi1, a component of
      the replication fork protection complex, and multiple Rad22 DNA repair foci were
      frequently observed in Tel2-repressed swi1Delta cells especially at S phase. In
      contrast, the cds1Deltaswi1Delta mutant did not show such lethality. These
      results indicate that S. pombe Tel2 plays important roles in the Mrc1-mediated
      replication checkpoint as well as in the Cds1-independent regulation of genome
      integrity.

PMID- 17189248
TI  - Phosphorylation of human CTP synthetase 1 by protein kinase A: identification of
      Thr455 as a major site of phosphorylation.
AB  - CTP synthetase is an essential enzyme that generates the CTP required for the
      synthesis of nucleic acids and membrane phospholipids. In this study, we examined
      the phosphorylation of the human CTPS1-encoded CTP synthetase 1 by protein kinase
      A. CTP synthetase 1 was expressed and purified from a Saccharomyces cerevisiae
      ura7Delta ura8Delta double mutant that lacks CTP synthetase activity. Using
      purified CTP synthetase 1 as a substrate, protein kinase A activity was time- and
      dose-dependent. The phosphorylation, which primarily occurred on a threonine
      residue, was accompanied by a 50% decrease in CTP synthetase 1 activity. The
      synthetic peptide LGKRRTLFQT that contains the protein kinase A motif for
      Thr(455) was a substrate for protein kinase A. A Thr(455) to Ala (T455A) mutation
      in CTP synthetase 1 was constructed by site-directed mutagenesis and was
      expressed and purified from the S. cerevisiae ura7Delta ura8Delta mutant. The
      T455A mutation caused a 78% decrease in protein kinase A phosphorylation and the
      loss of the phosphothreonine residue and a major phosphopeptide that were present
      in the purified wild type enzyme phosphorylated by protein kinase A. The CTP
      synthetase 1 activity of the T455A mutant enzyme was 2-fold higher than the wild
      type enzyme. In addition, the T455A mutation caused a 44% decrease in the amount
      of human CTP synthetase 1 that was phosphorylated in S. cerevisiae cells, and
      this was accompanied by a 2.5-fold increase in the cellular concentration of CTP
      and a 1.5-fold increase in the choline-dependent synthesis of
      phosphatidylcholine.

PMID- 17189250
TI  - Organization and function of the YsiA regulon of Bacillus subtilis involved in
      fatty acid degradation.
AB  - The organization and function of the Bacillus subtilis YsiA regulon involved in
      fatty acid degradation were investigated. Northern and primer extension analyses
      indicated that this regulon comprises five operons, i.e. lcfA-ysiA-B-etfB-A, ykuF
      G, yhfL, yusM-L-K-J, and ywjF-acdA-rpoE. YusJ and AcdA, YsiB and YusL, and YusK
      presumably encode acyl-CoA dehydrogenases, 3-hydroxyl-CoA dehydrogenase/enoyl-CoA
      hydratase complexes, and acetyl-CoA C-acyltransferase, respectively, which are
      directly involved in the fatty acid beta-oxidation cycle. In addition, LcfA and
      YhfL are likely to encode long chain acyl-CoA ligases. On gel retardation and
      footprinting analyses involving the purified YsiA protein, we identified cis
      sequences for YsiA binding (YsiA boxes) in the promoter regions upstream of ysiA,
      ykuF, yusL, yhfL, and ywjF, the equilibrium dissociation constants (K(d)) for
      YsiA binding being 20, 21, 37, 43, and 65 nm, respectively. YsiA binding was
      specifically inhibited by long chain acyl-CoAs with 14-20 carbon atoms, acyl-CoAs
      with 18 carbon atoms being more effective; out of long chain acyl-CoAs tested,
      monounsaturated oleoyl-CoA, and branched chain 12-metyltetradecanoyl-CoA were
      most effective. These in vitro findings were supported by the in vivo observation
      that the knock-out of acyl-CoA dehydrogenation through yusJ, etfA, or etfB
      disruption resulted in YsiA inactivation, probably because of the accumulation of
      long chain acyl-CoAs in the cells. Furthermore, the disruption of yusL, yusK,
      yusJ, etfA, etfB, or ykuG affected the utilization of palmitic acid, a
      representative long chain fatty acid. Based on this work, ysiA, ysiB, ykuF, ykuG,
      yhfL, yusM, yusL, yusK, yusJ, and ywjF can be renamed fadR, fadB, fadH, fadG,
      lcfB, fadM, fadN, fadA, fadE, and fadF.

PMID- 17189251
TI  - A new method of purification of proteasome substrates reveals polyubiquitination
      of 20 S proteasome subunits.
AB  - The 26 S proteasome is implicated in the control of many major biological
      functions but a reliable method for the identification of its major substrates,
      i.e. polyubiquitin (Ub) conjugates, is still lacking. Based on the steps present
      in cells, i.e. recognition and deubiquitination, we developed an affinity matrix
      based purification of polyUb conjugates suitable for any biological sample. Ub
      conjugates were first purified from proteasome inhibitor-treated C2C12 cells
      using the Ub binding domains of the S5a proteasome subunit bound to an affinity
      matrix and then deubiquitinated by the catalytic domain of the USP2 enzyme. This
      two step purification of proteasome substrates involving both protein-protein
      interactions and enzyme-mediated release allowed highly specific isolation of
      polyUb 26 S proteasome substrates, which were then resolved on two-dimensional
      gels post-deubiquitination. To establish our method, we focused on a gel area
      where spots were best resolved. Surprisingly, spot analysis by mass spectrometry
      identified alpha2, alpha6, alpha7, beta2, beta3, beta4, and beta5 20 S proteasome
      subunits as potential substrates. Western blots using an anti-beta3 proteasome
      subunit antibody confirmed that high molecular weight forms of beta3 were
      present, particularly in proteasome inhibitor-treated cells. Sucrose gradients of
      cell lysates suggested that the proteasome was first disassembled before subunits
      were polyubiquitinated. Altogether, we provide a technique that enables large
      scale identification of 26 S proteasome substrates that should contribute to a
      better understanding of this proteolytic machinery in any living cell and/or
      organ/tissue. Furthermore, the data suggest that proteasome homeostasis involves
      an autoregulatory mechanism.

PMID- 17189253
TI  - Src signaling regulates completion of abscission in cytokinesis through ERK/MAPK
      activation at the midbody.
AB  - Src family non-receptor-type tyrosine kinases regulate a wide variety of cellular
      events including cell cycle progression in G(2)/M phase. Here, we show that Src
      signaling regulates the terminal step in cytokinesis called abscission in HeLa
      cells. Abscission failure with an unusually elongated intercellular bridge
      containing the midbody is induced by treatment with the chemical Src inhibitors
      PP2 and SU6656 or expression of membrane-anchored Csk chimeras. By anti
      phosphotyrosine immunofluorescence and live cell imaging, completion of
      abscission requires Src-mediated tyrosine phosphorylation during early stages of
      mitosis (before cleavage furrow formation), which is subsequently delivered to
      the midbody through Rab11-driven vesicle transport. Treatment with U0126, a MEK
      inhibitor, decreases tyrosine phosphorylation levels at the midbody, leading to
      abscission failure. Activated ERK by MEK-catalyzed dual phosphorylation on
      threonine and tyrosine residues in the TEY sequence, which is strongly detected
      by anti-phosphotyrosine antibody, is transported to the midbody in a Rab11
      dependent manner. Src kinase activity during the early mitosis mediates ERK
      activation in late cytokinesis, indicating that Src-mediated signaling for
      abscission is spatially and temporally transmitted. Thus, these results suggest
      that recruitment of activated ERK, which is phosphorylated by MEK downstream of
      Src kinases, to the midbody plays an important role in completion of abscission.

PMID- 17189252
TI  - Nuclear and mitochondrial interaction involving mt-Nd2 leads to increased
      mitochondrial reactive oxygen species production.
AB  - NADH dehydrogenase subunit 2, encoded by the mtDNA, has been associated with
      resistance to autoimmune type I diabetes (T1D) in a case control study. Recently,
      we confirmed a role for the mouse ortholog of the protective allele (mt-Nd2(a))
      in resistance to T1D using genetic analysis of outcrosses between T1D-resistant
      ALR and T1D-susceptible NOD mice. We sought to determine the mechanism of disease
      protection by elucidating whether mt-Nd2(a) affects basal mitochondrial function
      or mitochondrial function in the presence of oxidative stress. Two lines of
      reciprocal conplastic mouse strains were generated: one with ALR nuclear DNA and
      NOD mtDNA (ALR.mt(NOD)) and the reciprocal with NOD nuclear DNA and ALR mtDNA
      (NOD.mt(ALR)). Basal mitochondrial respiration, transmembrane potential, and
      electron transport system enzymatic activities showed no difference among the
      strains. However, ALR.mt(NOD) mitochondria supported by either complex I or
      complex II substrates produced significantly more reactive oxygen species when
      compared with both parental strains, NOD.mt(ALR) or C57BL/6 controls. Nitric
      oxide inhibited respiration to a similar extent for mitochondria from the five
      strains due to competitive antagonism with molecular oxygen at complex IV.
      Superoxide and hydrogen peroxide generated by xanthine oxidase did not
      significantly decrease complex I function. The protein nitrating agents
      peroxynitrite or nitrogen dioxide radicals significantly decreased complex I
      function but with no significant difference among the five strains. In summary,
      mt-Nd2(a) does not confer elevated resistance to oxidative stress; however, it
      plays a critical role in the control of the mitochondrial reactive oxygen species
      production.

PMID- 17189254
TI  - Mechanisms of plasmin-catalyzed inactivation of factor VIII: a crucial role for
      proteolytic cleavage at Arg336 responsible for plasmin-catalyzed factor VIII
      inactivation.
AB  - Plasmin not only functions as a key enzyme in the fibrinolytic system but also
      directly inactivates factor VIII and other clotting factors such as factor V.
      However, the mechanisms of plasmin-catalyzed factor VIII inactivation are poorly
      understood. In this study, levels of factor VIII activity increased approximately
      2-fold within 3 min in the presence of plasmin, and subsequently decreased to
      undetectable levels within 45 min. This time-dependent reaction was not affected
      by von Willebrand factor and phospholipid. The rate constant of plasmin-catalyzed
      factor VIIIa inactivation was approximately 12- and approximately 3.7-fold
      greater than those mediated by factor Xa and activated protein C, respectively.
      SDS-PAGE analysis showed that plasmin cleaved the heavy chain of factor VIII into
      two terminal products, A1(37-336) and A2 subunits, by limited proteolysis at
      Lys(36), Arg(336), Arg(372), and Arg(740). The 80-kDa light chain was converted
      into a 67-kDa subunit by cleavage at Arg(1689) and Arg(1721), identical to the
      pattern induced by factor Xa. Plasmin-catalyzed cleavage at Arg(336) proceeded
      faster than that at Arg(372), in contrast to proteolysis by factor Xa.
      Furthermore, breakdown was faster than that in the presence of activated protein
      C, consistent with rapid inactivation of factor VIII. The cleavages at Arg(336)
      and Lys(36) occurred rapidly in the presence of A2 and A3-C1-C2 subunits,
      respectively. These results strongly indicated that cleavage at Arg(336) was a
      central mechanism of plasmin-catalyzed factor VIII inactivation. Furthermore, the
      cleavages at Arg(336) and Lys(36) appeared to be selectively regulated by the A2
      and A3-C1-C2 domains, respectively, interacting with plasmin.

PMID- 17189255
TI  - Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at
      the Thr-2609 cluster upon DNA double strand break.
AB  - The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is rapidly
      phosphorylated at the Thr-2609 cluster and Ser-2056 upon ionizing radiation (IR).
      Furthermore, DNA-PKcs phosphorylation at both regions is critical for its role in
      DNA double strand break (DSB) repair as well as cellular resistance to radiation.
      IR-induced DNA-PKcs phosphorylation at Thr-2609 and Ser-2056, however, exhibits
      distinct kinetics indicating that they are differentially regulated. Although DNA
      PKcs autophosphorylates itself at Ser-2056 after IR, we have reported here that
      ATM mediates DNA-PKcs phosphorylation at Thr-2609 as well as at the adjacent
      (S/T)Q motifs within the Thr-2609 cluster. In addition, our data suggest that DNA
      PKcs- and ATM-mediated DNA-PKcs phosphorylations are cooperative and required for
      the full activation of DNA-PKcs and the subsequent DSB repair. Elimination of DNA
      PKcs phosphorylation at both regions severely compromises radioresistance and DSB
      repair. Finally, our result provides a possible mechanism for the direct
      involvement of ATM in non-homologous end joining-mediated DSB repair.

PMID- 17189256
TI  - Defining the native disulfide topology in the somatomedin B domain of human
      vitronectin.
AB  - The N-terminal 44 amino acid residues of the human plasma glycoprotein
      vitronectin, known as the somatomedin B (SMB) domain, mediates the interaction
      between vitronectin and plasminogen activator inhibitor 1 (PAI-1) in a variety of
      important biological processes. Despite the functional importance of the Cys-rich
      SMB domain, how its four disulfide bridges are arranged in the molecule remains
      highly controversial, as evidenced by three different disulfide connectivities
      reported by several laboratories. Using native chemical ligation and orthogonal
      protection of selected Cys residues, we chemically synthesized all three
      topological analogs of SMB with predefined disulfide connectivities corresponding
      to those previously published. In addition, we oxidatively folded a fully reduced
      SMB in aqueous solution, and prepared, by CNBr cleavage, the N-terminal segment
      of 51 amino acid residues of intact vitronectin purified from human blood.
      Proteolysis coupled with mass spectrometric analysis and functional
      characterization using a surface plasmon resonance based vitronectin-PAI-1-SMB
      competition assay allowed us to conclude that 1) only the Cys(5)-Cys(21), Cys(9)
      Cys(39), Cys(19)-Cys(32), and Cys(25)-Cys(31) connectivity is present in native
      vitronectin; 2) only the native disulfide connectivity is functional; and 3) the
      native disulfide pairings can be readily formed during spontaneous (oxidative)
      folding of the SMB domain in vitro. Our results unequivocally define the native
      disulfide topology in the SMB domain of human vitronectin, providing biochemical
      as well as functional support to the structural findings on a recombinant SMB
      domain by Read and colleagues (Zhou, A., Huntington, J. A., Pannu, N. S.,
      Carrell, R. W., and Read, R. J. (2003) Nat. Struct. Biol. 10, 541-544).

PMID- 17189257
TI  - Analysis of lipolytic protein trafficking and interactions in adipocytes.
AB  - This work examined the colocalization, trafficking, and interactions of key
      proteins involved in lipolysis during brief cAMP-dependent protein kinase A (PKA)
      activation. Double label immunofluorescence analysis of 3T3-L1 adipocytes
      indicated that PKA activation increases the translocation of hormonesensitive
      lipase (HSL) to perilipin A (Plin)-containing droplets and increases the
      colocalization of adipose tissue triglyceride lipase (Atgl) with its coactivator,
      Abhd5. Imaging of live 3T3-L1 preadipocytes transfected with Aquorea victoria
      based fluorescent reporters demonstrated that HSL rapidly and specifically
      translocates to lipid droplets (LDs) containing Plin, and that this translocation
      is partially dependent on Plin phosphorylation. HSL closely, if not directly,
      interacts with Plin, as indicated by fluorescence resonance energy transfer
      (FRET) and bimolecular fluorescence complementation (BiFC) experiments. In
      contrast, tagged Atgl did not support FRET or BiFC with Plin, although it did
      modestly translocate to LDs upon stimulation. Abhd5 strongly interacted with Plin
      in the basal state, as indicated by FRET and BiFC. PKA activation rapidly (within
      minutes) decreased FRET between Abhd5 and Plin, and this decrease depended upon
      Plin phosphorylation. Together, these results indicate that Plin mediates hormone
      stimulated lipolysis via direct and indirect mechanisms. Plin indirectly controls
      Atgl activity by regulating accessibility to its coactivator, Abhd5. In contrast,
      Plin directly regulates the access of HSL to substrate via close, if not direct,
      interactions. The differential interactions of HSL and Atgl with Plin and Abhd5
      also explain the findings that following stimulation, HSL and Atgl are
      differentially enriched at specific LDs.

PMID- 17189258
TI  - Characterization of myelin ligand complexes with neuronal Nogo-66 receptor family
      members.
AB  - Nogo, MAG, and OMgp are myelin-associated proteins that bind to a neuronal Nogo
      66 receptor (NgR/NgR1) to limit axonal regeneration after central nervous system
      injury. Within Nogo-A, two separate domains are known interact with NgR1. NgR1 is
      the founding member of the three-member NgR family, whereas Nogo-A (RTN4A)
      belongs to a four-member reticulon family. Here, we systematically mapped the
      interactions between these superfamilies, demonstrating novel nanomolar
      interactions of RTN2 and RTN3 with NgR1. Because RTN3 is expressed in spinal cord
      white matter, it may have a role in myelin inhibition of axonal growth. Further
      analysis of the Nogo-A and NgR1 interactions revealed a novel third interaction
      site between the proteins, suggesting a trivalent Nogo-A interaction with NgR1.
      We also confirmed here that MAG binds to NgR2, but not to NgR3. Unexpectedly, we
      found that OMgp interacts with MAG with a higher affinity compared with NgR1. To
      better define how these multiple structurally distinct ligands bind to NgR1, we
      examined a series of Ala-substituted NgR1 mutants for ligand binding activity. We
      found that the core of the binding domain is centered in the middle of the
      concave surface of the NgR1 leucine-rich repeat domain and surrounded by
      differentially utilized residues. This detailed knowledge of the molecular
      interactions between NgR1 and its ligands is imperative when assessing options
      for development of NgR1-based therapeutics for central nervous system injuries.

PMID- 17189259
TI  - Fast and selective ammonia transport by aquaporin-8.
AB  - The transport of ammonia/ammonium is fundamental to nitrogen metabolism in all
      forms of life. So far, no clear picture has emerged as to whether a protein
      channel is capable of transporting exclusively neutral NH(3) while excluding H(+)
      and NH(4)(+). Our research is the first stoichiometric study to show the
      selective transport of NH(3) by a membrane channel. The purified water channel
      protein aquaporin-8 was reconstituted into planar bilayers, and the exclusion of
      NH(4)(+) or H(+) was established by ensuring a lack of current under voltage
      clamp conditions. The single channel water permeability coefficient of 1.2 x 10(
      14) cm(3)/subunit/s was established by imposing an osmotic gradient across
      reconstituted planar bilayers, and resulting minute changes in ionic
      concentration close to the membrane surface were detected. It is more than 2-fold
      smaller than the single channel ammonia permeability (2.7 x 10(-14)
      cm(3)/subunit/s) that was derived by establishing a transmembrane ammonium
      concentration gradient and measuring the resulting concentration increases
      adjacent to the membrane. This permeability ratio suggests that electrically
      silent ammonia transport may be the main function of AQP8.

PMID- 17189260
TI  - Reversal of agonist selectivity by mutations of conserved amino acids in the
      binding site of nicotinic acetylcholine receptors.
AB  - Homomeric alpha7 and heteromeric alpha4beta2 nicotinic acetylcholine receptors
      (nAChR) can be distinguished by their pharmacological properties, including
      agonist specificity. We introduced point mutations of conserved amino acids
      within the C loop, a region of the receptor critical for agonist binding, and we
      examined the expression of the mutant receptors in Xenopus oocytes. Mutation of
      either a conserved C loop tyrosine (188) to phenylalanine or a nearby conserved
      aspartate (197) to alanine resulted in alpha7 receptors for which the alpha7
      selective agonist 3-(4-hydroxy, 2-methoxybenzylidene) anabaseine (4OH-GTS-21) had
      roughly the same potency as for wild-type receptors, whereas the physiologic
      agonist acetylcholine (ACh) showed drastically reduced potency for these mutant
      receptors. Corresponding mutations in alpha4 receptors co-expressed with beta2
      resulted in alpha4beta2 receptors for which ACh potency was relatively unchanged,
      although the efficacy of the alpha7-selective agonist 4OH-GTS-21 was increased
      greatly relative to that of ACh. We also investigated the significance of a
      conserved lysine (145 in alpha7), proposed to form a stable salt bridge with Asp
      197 in the resting state of the receptor. Mutations of this residue in both
      alpha7 and alpha4 resulted in receptors that were largely unresponsive to both
      ACh and 4OH-GTS-21. Our results suggest that initiation of gating depends both on
      specific interactions between residues in the C loop domain and, depending on
      receptor subtype, the physiochemical properties of the agonist, so that in the
      altered environment of the alpha4Y190F-binding site, large hydrophobic
      benzylidene anabaseines may close the C loop and initiate channel gating more
      effectively than the polar agonist ACh.

PMID- 17189261
TI  - Methyltransferase that modifies guanine 966 of the 16 S rRNA: functional
      identification and tertiary structure.
AB  - N(2)-Methylguanine 966 is located in the loop of Escherichia coli 16 S rRNA helix
      31, forming a part of the P-site tRNA-binding pocket. We found yhhF to be a gene
      encoding for m(2)G966 specific 16 S rRNA methyltransferase. Disruption of the
      yhhF gene by kanamycin resistance marker leads to a loss of modification at G966.
      The modification could be rescued by expression of recombinant protein from the
      plasmid carrying the yhhF gene. Moreover, purified m(2)G966 methyltransferase, in
      the presence of S-adenosylomethionine (AdoMet), is able to methylate 30 S
      ribosomal subunits that were purified from yhhF knock-out strain in vitro. The
      methylation is specific for G966 base of the 16 S rRNA. The m(2)G966
      methyltransferase was crystallized, and its structure has been determined and
      refined to 2.05A(.) The structure closely resembles RsmC rRNA methyltransferase,
      specific for m(2)G1207 of the 16 S rRNA. Structural comparisons and analysis of
      the enzyme active site suggest modes for binding AdoMet and rRNA to m(2)G966
      methyltransferase. Based on the experimental data and current nomenclature the
      protein expressed from the yhhF gene was renamed to RsmD. A model for interaction
      of RsmD with ribosome has been proposed.

PMID- 17189262
TI  - Effect of 4-hydroxy-2-nonenal modification on alpha-synuclein aggregation.
AB  - Several observations have implicated oxidative stress and aggregation of the
      presynaptic protein alpha-synuclein in the pathogenesis of Parkinson disease.
      alpha-Synuclein has been shown to have affinity for unsaturated fatty acids and
      membranes enriched in polyunsaturated fatty acids, which are especially sensitive
      to oxidation under conditions of oxidative stress. One of the most important
      products of lipid oxidation is 4-hydroxy-2-nonenal (HNE), which has been
      implicated in the pathogenesis of Parkinson disease. Consequently, we
      investigated the effects of the interaction of HNE with alpha-synuclein.
      Incubation of HNE with alpha-synuclein at pH 7.4 and 37 degrees C resulted in
      covalent modification of the protein, with up to six HNE molecules incorporated
      as Michael addition products. Fourier transform infrared and CD spectra indicated
      that HNE modification of alpha-synuclein resulted in a major conformational
      change involving increased beta-sheet. HNE modification of alpha-synuclein led to
      inhibition of fibrillation in an HNE concentration-dependent manner. This
      inhibition of fibrillation was shown to be due to the formation of soluble
      oligomers based on size exclusion high pressure liquid chromatography and atomic
      force microscope data. Small angle x-ray scattering analysis indicated that the
      HNE-induced oligomers were compact and tightly packed. Treatment with guanidinium
      chloride demonstrated that the HNE-induced oligomers were very stable with an
      extremely slow rate of dissociation. Addition of 5 mum HNE-modified oligomers to
      primary mesencephalic cultures caused marked neurotoxicity because the integrity
      of dopaminergic and GABAergic neurons was reduced by 95 and 85%, respectively.
      Our observations indicate that HNE modification of alpha-synuclein prevents
      fibrillation but may result in toxic oligomers, which could therefore contribute
      to the demise of neurons subjected to oxidative damage.

PMID- 17189263
TI  - Calcium-dependent regulation of protein kinase D revealed by a genetically
      encoded kinase activity reporter.
AB  - Protein kinase D (PKD) regulates many diverse cellular functions in response to
      diacylglycerol. To monitor PKD signaling in live cells, we generated a
      genetically encoded fluorescent reporter for PKD activity, DKAR (D kinase
      activity reporter). DKAR expressed in mammalian cells undergoes reversible
      fluorescence resonance energy transfer changes upon activation and inhibition of
      endogenous PKD. Surprisingly, we find that agonist-evoked activation of PKD is
      driven not only by diacylglycerol production, but by Ca(2+). Furthermore,
      elevation of intracellular Ca(2+), in the absence of any other stimulus, is
      sufficient to activate PKD. Concurrent imaging of Ca(2+), diacylglycerol, and PKD
      activity reveals that thapsigargin-mediated elevation of intracellular Ca(2+) is
      closely followed by a robust increase in diacylglycerol production, in turn
      followed by PKD activation. The Ca(2+)-induced production of diacylglycerol and
      accompanying PKD activation is dependent on phospholipase C activity. These data
      reveal that Ca(2+) is a major contributor to the initiation of PKD signaling
      through positive feedback regulation of diacylglycerol production, unveiling a
      new mechanism in PKD activation.

PMID- 17189265
TI  - Human xylosyltransferase II is involved in the biosynthesis of the uniform
      tetrasaccharide linkage region in chondroitin sulfate and heparan sulfate
      proteoglycans.
AB  - Human xylosyltransferase I (XT-I) initiates the biosynthesis of the
      glycosaminoglycan (GAG) linkage tetrasaccharide in proteoglycans.
      Xylosyltransferase II (XT-II) is a protein homologous to XT-I but with hitherto
      unknown activity or physiological function. Here, we report the enzymatic
      activity of XT-II and provide evidence that XT-II initiates the biosynthesis of
      both heparan sulfate and chondroitin sulfate GAGs. Transfection of the
      xylosyltransferase-deficient Chinese hamster ovary mutant pgsA-745 with XT-I or
      XT-II coding cDNA completely restored GAG biosynthesis. GAG disaccharide analysis
      revealed that XT-I- and XT-II-transfected pgsA-745 cells produced similar amounts
      of chondroitin sulfate and heparan sulfate. Furthermore, a high
      xylosyltransferase activity was measured after transfection with cDNAs encoding
      either isozyme. Analysis of the enzyme activity revealed that XT-II catalyzes the
      transfer of xylose to similar peptide acceptors as XT-I but with different
      efficiency. The optimal XT-II acceptor was observed using a bikunin-related
      peptide (K(m) 5.2 microM). Analysis of XT-I and XT-II mRNA expression in murine
      tissues showed a differential expression pattern for both enzymes. In particular,
      XT-II is highly expressed in liver tissue, where XT-I transcripts were not
      detected. This is the first report on the enzyme activity of XT-II and its
      involvement in chondroitin sulfate and heparan sulfate biosynthesis.

PMID- 17189266
TI  - Biosynthesis of chondroitin and heparan sulfate in chinese hamster ovary cells
      depends on xylosyltransferase II.
AB  - Xylosyltransferase (XylT) catalyzes the initial enzymatic reaction in the
      glycosaminoglycan assembly pathway for proteoglycan biosynthesis. Its activity is
      thought to be rate-limiting. Two xylosyltransferases have been found using
      genomic analyses, and one of these, XylT1, has been shown to have
      xylosyltransferase activity. On the other hand, the less studied XylT2 in
      recombinant form lacks xylosyltransferase activity and has no known function.
      Wild-type Chinese hamster ovary cells express abundant Xylt2 mRNA levels and lack
      detectable Xylt1 mRNA levels. Analysis of a previously described Chinese hamster
      ovary cell xylosyltransferase mutant (psgA-745) shows that it harbors an Xylt2
      nonsense mutation and fails to assemble glycosaminoglycans onto recombinant
      biglycan. Transfection of this cell line with a murine Xylt2 minigene results in
      the production of recombinant chondroitin sulfate-modified biglycan core protein
      and restoration of fibroblast growth factor binding to cell surface-associated
      heparan sulfate. Expression analyses on 10 different human transformed cell lines
      detect exclusive XYLT2 expression in two and co-expression of XYLT1 and XYLT2 in
      the others but at disparate ratios where XYLT2 expression is greater than XYLT1
      in most cell lines. These results indicate that XylT2 has a significant role in
      proteoglycan biosynthesis and that cell type may control which family member is
      utilized.

PMID- 17189264
TI  - Identification of histone H3 lysine 36 acetylation as a highly conserved histone
      modification.
AB  - Histone lysine acetylation is a major mechanism by which cells regulate the
      structure and function of chromatin, and new sites of acetylation continue to be
      discovered. Here we identify and characterize histone H3K36 acetylation
      (H3K36ac). By mass spectrometric analyses of H3 purified from Tetrahymena
      thermophila and Saccharomyces cerevisiae (yeast), we find that H3K36 can be
      acetylated or methylated. Using an antibody specific to H3K36ac, we show that
      this modification is conserved in mammals. In yeast, genome-wide ChIP-chip
      experiments show that H3K36ac is localized predominantly to the promoters of RNA
      polymerase II-transcribed genes, a pattern inversely related to that of H3K36
      methylation. The pattern of H3K36ac localization is similar to that of other
      sites of H3 acetylation, including H3K9ac and H3K14ac. Using histone
      acetyltransferase complexes purified from yeast, we show that the Gcn5-containing
      SAGA complex that regulates transcription specifically acetylates H3K36 in vitro.
      Deletion of GCN5 completely abolishes H3K36ac in vivo. These data expand our
      knowledge of the genomic targets of Gcn5, show H3K36ac is highly conserved, and
      raise the intriguing possibility that the transition between H3K36ac and H3K36me
      acts as an "acetyl/methyl switch" governing chromatin function along
      transcription units.

PMID- 17189267
TI  - Knockdown of mitochondrial heat shock protein 70 promotes progeria-like
      phenotypes in caenorhabditis elegans.
AB  - Mitochondrial heat shock protein 70 (mthsp70) functions as a mitochondrial import
      motor and is essential in mitochondrial biogenesis and energy generation in
      eukaryotic cells. HSP-6 (hsp70F) is a nematode orthologue of mthsp70. Knockdown
      of HSP-6 by RNA interference in young adult nematodes caused a reduction in the
      levels of ATP-2, HSP-60 and CLK-1, leading to abnormal mitochondrial morphology
      and lower ATP levels. As a result, RNA interference-treated worms had lower
      motility, defects in oogenesis, earlier accumulation of autofluorescent material,
      and a shorter life span. These are the major phenotypes observed during the aging
      of worms, suggesting that the reduction of HSP-6 causes early aging or progeria
      like phenotypes. The amount of HSP-6 became dramatically reduced at the expected
      mean life span in not only wild-type but also in long and short life span mutant
      worms (wild-type, daf-2, and daf-16). Mitochondrial HSP-60 and ATP-2 were also
      reduced following the reduction of HSP-6 during aging. These results suggest that
      the reduction of HSP-6 causes defects in mitochondrial function at the final
      stage of aging, leading to mortality.

PMID- 17189268
TI  - Interferon regulatory factor-8 is indispensable for the expression of
      promyelocytic leukemia and the formation of nuclear bodies in myeloid cells.
AB  - Interferon (IFN) regulatory factor-8 (IRF-8), previously known as ICSBP, is a
      myeloid cell essential transcription factor. Mice with null mutation in IRF-8 are
      defective in the ability of myeloid progenitor cells to mature toward macrophage
      lineage. Accordingly, these mice develop chronic myelogenous leukemia (CML). We
      demonstrate here that IRF-8 is an obligatory regulator of the promyelocytic
      leukemia (PML) gene in activated macrophages, leading to the expression of the
      PML-I isoform. This regulation is most effective together with two other
      transcription factors, IRF-1 and PU.1. PML is a tumor suppressor gene that serves
      as a scaffold protein for nuclear bodies. IRF-8 is not only essential for the IFN
      gamma-induced expression of PML in activated macrophages but also for the
      formation of nuclear bodies. Reduced IRF-8 transcript levels were reported in CML
      patients, and a recovery to normal levels was observed in patients in remission
      following treatment with IFN-alpha. We demonstrate a significant correlation
      between the levels of IRF-8 and PML in these CML patients. Together, our results
      indicate that some of the myeloleukemia suppressor activities of IRF-8 are
      mediated through the regulation of PML. When IRF-8 levels are compromised, the
      reduced PML expression may lead to genome instability and eventually to the
      leukemic phenotype.

PMID- 17189269
TI  - The novel cellular mechanism of human 5-HT6 receptor through an interaction with
      Fyn.
AB  - The human 5-HT(6) receptor (5-HT(6)R) is one of the latest cloned receptors among
      the known 5-HT receptors. Its abundant distribution in the limbic region, which
      participates in the control of mood and emotion and is involved in nervous system
      diseases such as depression and Alzheimer disease, has caused it to generate much
      interest. However, the cellular mechanisms of 5-HT(6)R are poorly understood. In
      the present study we found, using a yeast two-hybrid assay, that the carboxyl
      terminal region of 5-HT(6)R interacts with the Fyn-tyrosine kinase. We also
      determined using a glutathione S-transferase pulldown assay that this interaction
      was mediated through the SH3 domain of Fyn and confirmed this by co
      immunoprecipitation assays in two different transfected cell lines as well as in
      adult rat brains. Immunocyto(histo)chemistry also showed prominent co
      localization between 5-HT(6)R and Fyn in transfected cells and a similar
      distribution between 5-HT(6)R and Fyn in the rat brain. Based on this
      interaction, we further examined the modulation of 5-HT(6)R by Fyn and vice
      versa. In addition, we demonstrated that the activation of 5-HT(6)R activated the
      extracellular signal-regulated kinase1/2 via an Fyn-dependent pathway. These
      findings suggest that Fyn may play an important role in 5-HT(6)R- mediated
      signaling pathways in the central nervous system.

PMID- 17189270
TI  - alpha-Synuclein stimulates differentiation of osteosarcoma cells: relevance to
      down-regulation of proteasome activity.
AB  - Because a limited study previously showed that alpha-synuclein (alpha-syn), the
      major pathogenic protein for Parkinson disease, was expressed in differentiating
      brain tumors as well as various peripheral cancers, the main objective of the
      present study was to determine whether alpha-syn might be involved in the
      regulation of tumor differentiation. For this purpose, alpha-syn and its non
      amyloidogenic homologue beta-syn were stably transfected to human osteosarcoma
      MG63 cell line. Compared with beta-syn-overexpressing and vector-transfected
      cells, alpha-syn-overexpressing cells exhibited distinct features of
      differentiated osteoblastic phenotype, as shown by up-regulation of alkaline
      phosphatase and osteocalcin as well as inductive matrix mineralization. Further
      studies revealed that proteasome activity was significantly decreased in alpha
      syn-overexpressing cells compared with other cell types, consistent with the fact
      that proteasome inhibitors stimulate differentiation of various osteoblastic
      cells. In alpha-syn-overexpressing cells, protein kinase C (PKC) activity was
      significantly decreased, and reactivation of PKC by phorbol ester significantly
      restored the proteasome activity and abrogated cellular differentiation.
      Moreover, activity of lysosome was up-regulated in alpha-syn-overexpressing
      cells, and treatment of these cells with autophagy-lysosomal inhibitors resulted
      in a decrease of proteasome activity associated with up-regulation of alpha-syn
      expression, leading to enhance cellular differentiation. Taken together, these
      results suggest that the stimulatory effect of alpha-syn on tumor differentiation
      may be attributed to down-regulation of proteasome, which is further modulated by
      alterations of various factors, such as protein kinase C signaling pathway and a
      autophagy-lysosomal degradation system. Thus, the mechanism of alpha-syn
      regulation of tumor differentiation and neuropathological effects of alpha-syn
      may considerably overlap with each other.

PMID- 17189271
TI  - Ectopic expression of dentin sialoprotein during amelogenesis hardens bulk
      enamel.
AB  - Dentin sialophosphpoprotein (Dspp) is transiently expressed in the early stage of
      secretory ameloblasts. The secretion of ameloblast-derived Dspp is short-lived,
      correlates to the establishment of the dentinoenamel junction (DEJ), and is
      consistent with Dspp having a role in producing the specialized first-formed
      harder enamel adjacent to the DEJ. Crack diffusion by branching and dissipation
      within this specialized first-formed enamel close to the DEJ prevents
      catastrophic interfacial damage and tooth failure. Once Dspp is secreted, it is
      subjected to proteolytic cleavage that results in two distinct proteins referred
      to as dentin sialoprotein (Dsp) and dentin phosphoprotein (Dpp). The purpose of
      this study was to investigate the biological and mechanical contribution of Dsp
      and Dpp to enamel formation. Transgenic mice were engineered to overexpress
      either Dsp or Dpp in their enamel organs. The mechanical properties (hardness and
      toughness) of the mature enamel of transgenic mice were compared with genetically
      matched and age-matched nontransgenic animals. Dsp and Dpp contributions to
      enamel formation greatly differed. The inclusion of Dsp in bulk enamel
      significantly and uniformly increased enamel hardness (20%), whereas the
      inclusion of Dpp weakened the bulk enamel. Thus, Dsp appears to make a unique
      contribution to the physical properties of the DEJ. Dsp transgenic animals have
      been engineered with superior enamel mechanical properties.

PMID- 17189272
TI  - Reaction mechanism of pyridoxal 5'-phosphate synthase. Detection of an enzyme
      bound chromophoric intermediate.
AB  - Vitamin B6 is an essential metabolite in all organisms. De novo synthesis of the
      vitamin can occur through either of two mutually exclusive pathways referred to
      as deoxyxylulose 5-phosphate-dependent and deoxyxylulose 5-phosphate-independent.
      The latter pathway has only recently been discovered and is distinguished by the
      presence of two genes, Pdx1 and Pdx2, encoding the synthase and glutaminase
      subunit of PLP synthase, respectively. In the presence of ammonia, the synthase
      alone displays an exceptional polymorphic synthetic ability in carrying out a
      complex set of reactions, including pentose and triose isomerization, imine
      formation, ammonia addition, aldol-type condensation, cyclization, and
      aromatization, that convert C3 and C5 precursors into the cofactor B6 vitamer,
      pyridoxal 5'-phosphate. Here, employing the Bacillus subtilis proteins, we
      demonstrate key features along the catalytic path. We show that ribose 5
      phosphate is the preferred C5 substrate and provide unequivocal evidence that the
      pent(ul)ose phosphate imine occurs at lysine 81 rather than lysine 149 as
      previously postulated. While this study was under review, corroborative
      crystallographic evidence has been provided for imine formation with the
      corresponding lysine group in the enzyme from Thermotoga maritima (Zein, F.,
      Zhang, Y., Kang, Y.-N., Burns, K., Begley, T. P., and Ealick, S. E. (2006)
      Biochemistry 45, 14609-14620). We have detected an unanticipated covalent
      reaction intermediate that occurs subsequent to imine formation and is dependent
      on the presence of Pdx2 and glutamine. This step most likely primes the enzyme
      for acceptance of the triose sugar, ultimately leading to formation of the
      pyridine ring. Two alternative structures are proposed for the chromophoric
      intermediate, both of which require substantial modifications of the proposed
      mechanism.

PMID- 17189274
TI  - Elucidation of the role of peptide linker in calcium-sensing receptor activation
      process.
AB  - Family 3 G-protein-coupled receptors (GPCRs), which includes metabotropic
      glutamate receptors (mGluRs), sweet and "umami" taste receptors (T1Rs), and the
      extracellular calcium-sensing receptor (CaR), represent a distinct group among
      the superfamily of GPCRs characterized by large amino-terminal extracellular
      ligand-binding domains (ECD) with homology to bacterial periplasmic amino acid
      binding proteins that are responsible for signal detection and receptor
      activation through as yet unresolved mechanism(s) via the seven-transmembrane
      helical domain (7TMD) common to all GPCRs. To address the mechanism(s) by which
      ligand-induced conformational changes are conveyed from the ECD to the 7TMD for G
      protein activation, we altered the length and composition of a 14-amino acid
      linker segment common to all family 3 GPCRs except GABA(B) receptor, in the CaR
      by insertion, deletion, and site-directed mutagenesis of specific highly
      conserved residues. Small alterations in the length and composition of the linker
      impaired cell surface expression and abrogated signaling of the chimeric
      receptors. The exchange of nine amino acids within the linker of CaR with the
      homologous sequence of mGluR1, however, preserved receptor function. Ala
      substitution for the four highly conserved residues within this amino acid
      sequence identified a Leu at position 606 of the CaR critical for cell surface
      expression and signaling. Substitution of Leu(606) for Ala resulted in impaired
      cell surface expression. However, Ile and Val substitutions displayed strong
      activating phenotypes. Disruption of the linker by insertion of nine amino acids
      of a random-coiled structure uncoupled the ECD from regulating the 7TMD. These
      data are consistent with a model of receptor activation in which the peptide
      linker, and particularly Leu(606), provides a critical interaction for the CaR
      signal transmission, a finding likely to be relevant for all family 3 GPCRs
      containing this conserved motif.

PMID- 17189273
TI  - Genetically altered expression of spermidine/spermine N1-acetyltransferase
      affects fat metabolism in mice via acetyl-CoA.
AB  - The acetylating enzyme, spermidine/spermine N1-acetyltransferase, participates in
      polyamine homeostasis by regulating polyamine export and catabolism. Previously,
      we reported that overexpression of the enzyme in cultured tumor cells and mice
      activates metabolic flux through the polyamine pathway and depletes the N1
      acetyltransferase coenzyme and fatty acid precursor, acetyl-CoA. Here, we
      investigate this possibility in spermidine/spermine N1-acetyltransferase
      transgenic mice in which the enzyme is systemically overexpressed and in
      spermidine/spermine N1-acetyltransferase knock-out mice. Tissues of the former
      were characterized by increased N1-acetyltransferase activity, a marked elevation
      in tissue and urinary acetylated polyamines, a compensatory increase in polyamine
      biosynthetic enzyme activity, and an increase in metabolic flux through the
      polyamine pathway. These polyamine effects were accompanied by a decrease in
      white adipose acetyl- and malonyl-CoA pools, a major (20-fold) increase in
      glucose and palmitate oxidation, and a distinctly lean phenotype. In SSAT-ko
      mice, the opposite relationship between polyamine and fat metabolism was
      observed. In the absence of N1-acetylation of polyamines, there was a shift in
      urinary and tissue polyamines indicative of a decline in metabolic flux. This was
      accompanied by an increase in white adipose acetyl- and malonyl-CoA pools, a
      decrease in adipose palmitate and glucose oxidation, and an accumulation of body
      fat. The latter was further exaggerated under a high fat diet, where knock-out
      mice gained twice as much weight as wild-type mice. A model is proposed whereby
      the expression status of spermidine/spermine N1-acetyltransferase alters body fat
      accumulation by metabolically modulating tissue acetyl- and malonyl-CoA levels,
      thereby influencing fatty acid biosynthesis and oxidation.

PMID- 17189275
TI  - HERG is protected from pharmacological block by alpha-1,2-glucosyltransferase
      function.
AB  - The HERG (human ether-a-go-go-related gene) protein, which underlies the cardiac
      repolarizing current I(Kr), is the unintended target for many pharmaceutical
      agents. Inadvertent block of I(Kr), known as the acquired long QT syndrome
      (aLQTS), is a leading cause for drug withdrawal by the United States Food and
      Drug Administration. Hence, an improved understanding of the regulatory factors
      that protect most individuals from aLQTS is essential for advancing clinical
      therapeutics in broad areas, from cancer chemotherapy to antipsychotics and
      antidepressants. Here, we show that the K(+) channel regulatory protein KCR1,
      which markedly reduces I(Kr) drug sensitivity, protects HERG through
      glucosyltransferase function. KCR1 and the yeast alpha-1,2-glucosyltransferase
      ALG10 exhibit sequence homology, and like KCR1, ALG10 diminished HERG block by
      dofetilide. Inhibition of cellular glycosylation pathways with tunicamycin
      abrogated the effects of KCR1, as did expression in Lec1 cells (deficient in
      glycosylation). Moreover, KCR1 complemented the growth defect of an alg10
      deficient yeast strain and enhanced glycosylation of an Alg10 substrate in yeast.
      HERG itself is not the target for KCR1-mediated glycosylation because the
      dofetilide response of glycosylation-deficient HERG(N598Q) was still modulated by
      KCR1. Nonetheless, our data indicate that the alpha-1,2-glucosyltransferase
      function is a key component of the molecular pathway whereby KCR1 diminishes
      I(Kr) drug response. Incorporation of in vitro data into a computational model
      indicated that KCR1 expression is protective against arrhythmias. These findings
      reveal a potential new avenue for targeted prevention of aLQTS.

PMID- 17189276
TI  - Calculated microdosimetric characteristics of 125I and 103Pd brachytherapy seeds
      at different depths in water.
AB  - Both (125)I and (103)Pd sources have been widely used in the permanent prostate
      implant. An important consideration for the choice of brachytherapy sources is
      the relative biological effectiveness (RBE) for the source/seed used in the
      implantation. As RBE is closely related to the microdosimetric parameter, it is
      desirable to calculate the dose mean lineal energies for both (125)I and (103)Pd
      at various radial distances to the seed surface. Monte Carlo simulation was
      performed for photons emitted from (125)I and (103)Pd. Energy depositions from
      photons and all their secondary electrons were tracked. Dose distributions of
      lineal energy, d(y), were calculated for spheres of 1 microm in diameter and at
      various radial distances to the seed surface. From the dose distribution of
      lineal energy, the dose mean lineal energy, y(D), was derived. The results showed
      that the radiation qualities are constant in the distance range from 0.5 to 5 cm.
      In this distance range, the quality factor, relative to gamma rays from (60)Co,
      is 2.2 for (125)I and 2.5 for (103)Pd.

PMID- 17189278
TI  - Workplace characterisation in case of rail transport of radioactive materials.
AB  - IRSN has been asked by SNCF (French Railways) to carry out measurements in order
      to establish the values of ambient dose equivalents H*(10) in the vicinity of
      shipments of radioactive materials to assess the external exposure to ionising
      radiation to which employees may be subjected during the carriage of radioactive
      goods. Detailed dosimetric characterisations of the wagons have been made and the
      external exposure at different stages of the work that is done by the employees
      have been measured in terms of H*(10). For the study presented in this paper, and
      corresponding to a used fuel shipment composed of UO2 and UO2-PuO2, it has been
      observed that the photon and neutron doses are very similar. In addition, the
      order of magnitude of the total dose integrated by an employee who would carry
      out 100 times the series of essential operational tasks, has been found to be
      approximately 250 microSv. This value is compared with those observed for other
      previously investigated shipments involving the exposure to photon fields only.

PMID- 17189277
TI  - Testing the stand-alone microbeam at Columbia University.
AB  - The stand-alone microbeam at Columbia University presents a novel approach to
      biological microbeam irradiation studies. Foregoing a conventional accelerator as
      a source of energetic ions, a small, high-specific-activity, alpha emitter is
      used. Alpha particles emitted from this source are focused using a compound
      magnetic lens consisting of 24 permanent magnets arranged in two quadrupole
      triplets. Using a 'home made' 6.5 mCi polonium source, a 1 alpha particle s(-1),
      10 microm diameter microbeam can, in principle, be realised. As the alpha source
      energy is constant, once the microbeam has been set up, no further adjustments
      are necessary apart from a periodic replacement of the source. The use of
      permanent magnets eliminates the need for bulky power supplies and cooling
      systems required by other types of ion lenses and greatly simplifies operation.
      It also makes the microbeam simple and cheap enough to be realised in any large
      lab. The Microbeam design as well as first tests of its performance, using an
      accelerator-based beam are presented here.

PMID- 17189279
TI  - Exposure of UK industrial plumbers to asbestos, Part II: Awareness and responses
      of plumbers to working with asbestos during a survey in parallel with personal
      sampling.
AB  - Throughout the European Union, millions tonnes of asbestos were used in the
      manufacture of products for building and for industrial installations. Today, in
      the UK, it is estimated that over half a million non-domestic premises alone have
      asbestos-containing materials in them and it is recognized that those working in
      building maintenance trades continue to be at significant risk. In part II, the
      awareness of UK plumbers to when they are working with asbestos was investigated
      and compared with the monitored levels reported in part I. The plumbers were
      issued by post with passive samplers, activity logs to monitor a working week and
      a questionnaire. The activity logs were used to assess whether maintenance
      workers were knowingly or unknowingly exposed to airborne asbestos fibres during
      a course of a working week. The questionnaire was designed to gather information
      on their: age, employment status, current and past perception of the frequency
      which they work with asbestos and knowledge of the precautions that should be
      taken to limit exposure and risk. Approximately 20% of workers reported on the
      sample log that they had worked with asbestos. There was a high correlation (93%)
      between the sampling log replies that they were knowingly working with asbestos
      and measured asbestos on the passive sampler. However, some 60% of the samples
      had >5 microm long asbestos structures found by transmission electron microscopy
      (TEM) analysis suggesting that the plumbers were aware of about only one-third of
      their contacts with asbestos materials throughout the week. This increased to
      just over one half of the plumbers being aware of their contact based on the
      results for phase contrast microscopy (PCM) countable asbestos fibres. The
      results from the questionnaire found that over half of the plumbers replying
      thought that they disturb asbestos only once a year and 90% of them thought they
      would work with asbestos for<10 h year-1. Their expectations and awareness of
      work with asbestos were therefore far lower than found during the period of
      monitoring. The response to an open question on the precautions to be taken,
      found that 61% of plumbers would avoid disturbance and 59% would use respiratory
      protection if they did disturb asbestos. However, their awareness of the methods
      and the need to reduce their risk by control of emissions at source was very low
      and suggests that further awareness raising and training is needed. The survey
      was carried out prior to the introduction of the duty to manage and gives a
      useful baseline to assess the impact of regulatory initiatives.

PMID- 17189280
TI  - Determination of occupational exposure to alkanolamines in metal-working fluids.
AB  - Overall exposure to alkanolamines in metal-working fluids (MWFs) in machine shops
      was studied by determining alkanolamines in air samples and in rinse-off samples
      from the hands of machinists. Methods for collecting airborne alkanolamines and
      alkanolamines absorbed to the skin of the hands were developed and tested. The
      exposure measurements were carried out in nine machine shops. After a 2 h working
      period the dominant hand of 37 machinists was rinsed with 200 ml of 20%
      isopropanol for 1 min in a plastic bag. Personal air samples were also collected
      during the 2 h working period onto acid-treated glass fibre filters. The filter
      samples were desorbed with methanol and analysed by liquid chromatography with
      mass spectrometric detection (LC-MS). The rinse-off samples were also analysed
      for alkanolamines by LC-MS. The median air concentration of monoethanolamine (EA)
      was 57 microg m-3, diethanolamine (DEA) 64 microg m-3 and triethanolamine (TEA) 6
      microg m-3. The workers' overall exposure to alkanolamines was estimated by
      calculating the amount in inhaled air and the amount on the skin. The median
      amount of EA on the skin of the dominant hand was 9-43 times the median amount in
      inhaled air during 2 h exposure. The corresponding ratio for DEA was 100 and for
      TEA 170. According to this study the exposure to alkanolamines occurs mainly
      through the skin. EA was the only alkanolamine with a noticeable inhalation
      uptake compared to the skin uptake. Total exposure to MWFs may be reduced by
      reducing skin exposure. The hand rinsing method can be used to assess the
      efficiency of protective gloves.

PMID- 17189281
TI  - Exposure of UK industrial plumbers to asbestos, Part I: Monitoring of exposure
      using personal passive samplers.
AB  - Epidemiological data suggest that there has been and may continue to be a
      significant risk to maintenance workers, who through their work may disturb
      asbestos-containing materials (ACM). The sampling and assessment of maintenance
      workers' exposure is a particular problem because they may not know that they are
      working with ACM. A strategy to monitor their true exposure has been developed
      and applied to one group of workers. The asbestos exposure of industrial plumbers
      was measured using personal passive samplers developed at the Health and Safety
      Laboratory (HSL). The light-weight samplers, which collect particles by
      electrostatic attraction, are simple to use and do not require prior knowledge
      that asbestos is to be disturbed as does conventional sampling. The samplers were
      issued by post and analysed, after return, using transmission electron microscopy
      (TEM). The strategy was found to be a reasonably efficient and cost-effective way
      to obtain data on maintenance worker's exposure to asbestos. The results of the
      TEM analysis of the passive samplers showed that the percentage of workers
      exposed to >5 microm long asbestos fibres was 62% in Round 1 and 58% in Round 2.
      For phase contrast microscopy equivalent (PCME) asbestos fibres, the values were
      46 and 29%, respectively. The three samples with the highest numbers of fibres
      were followed up and were associated with plumbers working in areas which had
      supposedly been stripped of asbestos just prior to their starting work,
      suggesting that poor removal, clean-up and clearance practice presents a
      significant part of the risk to plumbers. Although flow rates will vary with
      conditions and time, an approximate average sampling rate from previous
      comparisons was used to calculate the concentration. This gave an average
      exposure to regulated PCME fibres of 0.009 f ml-1 for amphibole asbestos and
      0.049 f ml-1 for chrysotile. The calculate risk based on the PCME fibre types
      collected and their estimated concentrations, showed that the risk from airborne
      amphibole fibres was approximately 6 times greater than from chrysotile fibres.
      If representative, the estimated lifetime risk of death from an asbestos related
      cancer for an exposure from age 20 for 40 years would be 68 per 100,000, which
      equates to an annual risk of death of the order of 10 per million.

PMID- 17189283
TI  - Thrombotic microangiopathy and anti-VEGF agents.

PMID- 17189282
TI  - Genome scan of glomerular filtration rate and albuminuria: the HyperGEN study.
AB  - BACKGROUND: Albuminuria and reduced glomerular filtration rate (GFR) are markers
      of renal dysfunction associated with hypertension. We performed genome-wide scans
      to detect loci impacting these parameters in 1251 African American (AAs) and 1129
      European American (EAs) hypertensive siblings from the Hypertension Genetic
      Epidemiology Network study. METHODS: GFR, estimated by the Modification of Diet
      in Renal Disease equation, and albuminuria, measured as albumin to creatinine
      ratio (ACR), were adjusted for gender, age, centre, mean blood pressure, anti
      hypertensive medication class and diabetes status using SOLAR. Since albuminuria
      and abnormal GFR often coexist, we conducted bivariate linkage analyses to
      investigate the presence of pleiotropy. RESULTS: The phenotypic correlation
      between ACR and GFR was not significant in EAs (r = 0.04) and significantly
      negative in AAs (r = -0.17). Univariate analyses of ACR showed suggestive
      evidence of linkage on chromosomes 8, 16 and 17 (LOD: 2-2.8) in AAs, on
      chromosomes 18 and 19 (LOD = 2) in EAs, and on chromosome 19 (LOD = 2.6) when
      combining AAs and EAs. For GFR, suggestive linkage was found on chromosomes 7, 14
      and 19 (LOD: 2.2-2.9) in AAs and on chromosomes 14, 15 and 16 (LOD: 2.1-3.3) in
      the combined group. Also, bivariate analyses showed a LOD score of 3.4 at 133 cM
      on chromosome 7 in AAs. CONCLUSIONS: Suggestive evidence for linkage to GFR and
      ACR was observed at many loci. The findings are consistent with previous studies.
      Also, indication of a pleiotropic locus was detected in chromosome 7 in AAs.

PMID- 17189284
TI  - Delirium and C-reactive protein.

PMID- 17189285
TI  - Vitamin B12 deficiency in the aged: a population-based study.
AB  - BACKGROUND: vitamin B12 deficiency is common in the aged, but it is controversial
      whether only some risk groups should be investigated instead of screening the
      entire aged population. OBJECTIVES: to describe the prevalence of vitamin B12
      deficiency in the Finnish aged, and to find out if the subjects especially prone
      to vitamin B12 deficiency could be identified by the risk factors or clinical
      correlates. DESIGN: a cross-sectional, population-based study of 1048 aged
      subjects (age 65-100 years) was carried out. Data on lifestyle factors and
      clinical conditions were collected, physical examinations were conducted and
      laboratory variables related to vitamin B12 were measured. RESULTS: vitamin B12
      deficiency had been previously diagnosed in 27 (2.6%) subjects, and a laboratory
      diagnosis (total vitamin B12 <150 pmol/l, or total vitamin B12 150-250 pmol/l and
      holotranscobalamin < or =37 pmol/l and homocysteine > or =15 micromol/l) was made
      for 97 (9.5%) subjects. Low serum total vitamin B12 (<150 pmol/l) was observed in
      6.1% and borderline total vitamin B12 (150-250 pmol/l) in 32% of the subjects.
      Male gender (OR 1.9, 95% CI 1.2-2.9), age > or =75 (OR 2.2, 95% CI 1.4-3.4) and
      refraining from milk products (OR 2.3, 95% CI 1.2-4.4) increased the probability
      for vitamin B12 deficiency. Anaemia (OR 1.3, 95% CI 0.7-2.3) or macrocytosis (OR
      1.2, 95% CI 0.6-2.7) did not predict vitamin B12 deficiency. CONCLUSION:
      undiagnosed vitamin B12 deficiency is remarkably common in the aged, but no
      specific risk group for screening can be identified. Thus, biochemical screening
      of unselected aged population is justified. General practitioners play a key role
      in diagnosing early vitamin B12 deficiency.

PMID- 17189286
TI  - Overexpression of Coptis japonica norcoclaurine 6-O-methyltransferase overcomes
      the rate-limiting step in Benzylisoquinoline alkaloid biosynthesis in cultured
      Eschscholzia californica.
AB  - Benzylisoquinoline alkaloids are one of the most important secondary metabolite
      groups, and include the economically important analgesic morphine and the
      antimicrobial agent berberine. To improve the production of these alkaloids, we
      investigated the effect of the overexpression of putative rate-limiting step
      enzymes in benzylisoquinoline alkaloid biosynthesis. We introduced two O
      methyltransferase [Coptis japonica norcoclaurine 6-O-methyltransferase (6OMT) and
      3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase (4'OMT)] expression vectors
      into cultured California poppy cells to avoid the gene silencing effect of
      endogenous genes. We established 20 independent lines for 6OMT transformants and
      15 independent lines for 4'OMT transformants. HPLC/liquid chromatography-mass
      spectrometry (LC-MS) analysis revealed that the overexpression of C. japonica
      6OMT was associated with an average alkaloid content 7.5 times greater than that
      in the wild type, whereas the overexpression of C. japonica 4'OMT had only a
      marginal effect. Further characterization of 6OMT in California poppy cells
      indicated that a 6OMT-specific gene is missing and 4OMT catalyzes the 6OMT
      reaction with low activity in California poppy, which supports the notion that
      the 6OMT reaction is important for alkaloid biosynthesis in this plant species.
      We discuss the importance of 6OMT in benzylisoquinoline alkaloid biosynthesis and
      the potential for using a rate-limiting step gene to improve alkaloid production.

PMID- 17189287
TI  - Molecular basis of late-flowering phenotype caused by dominant epi-alleles of the
      FWA locus in Arabidopsis.
AB  - The late-flowering phenotype of dominant fwa mutants is caused by hypomethylation
      in the FWA locus leading to ectopic expression of a homeodomain leucine zipper
      (HD-ZIP) protein. However, little is known about whether FWA has any role in
      regulation of flowering and how ectopically expressed FWA delays flowering.
      Through analysis of FWA expression in wild-type seedlings, it was shown that FWA
      is not expressed during the vegetative phase. This suggests that FWA has no role
      in flowering. The previous reports that fwa suppressed the precocious-flowering
      phenotype of plants overexpressing FLOWERING LOCUS T (FT) suggest that the
      flowering pathway(s) either at and/or downstream of FT is blocked by FWA.
      Comparison of gene expression profiles in three genetic backgrounds ectopically
      expressing FWA and their respective wild types failed to detect common changes,
      ruling out the possibility that FWA acts through transcriptional misregulation.
      Yeast two-hybrid analysis and in vitro pull-down assay showed that FWA protein
      can specifically interact with FT protein. The importance of protein interaction
      with FT in delaying flowering was supported by studies involving N-terminal and C
      terminal truncations of FWA. The C-terminal truncation with abolished interaction
      did not delay flowering when overexpressed, while the N-terminal truncation,
      which retains interaction, did. Specific interaction of FWA with FT enabled us to
      use FWA protein as a specific inhibitor of FT protein function. Through tissue
      specific ectopic expression of FWA, further support for the shoot apex being the
      site of action of FT protein was provided.

PMID- 17189288
TI  - Association of IRF5 in UK SLE families identifies a variant involved in
      polyadenylation.
AB  - Results from two studies have implicated the interferon regulatory gene IRF5 as a
      susceptibility gene in systemic lupus erythematosus (SLE). In this study, we
      conducted a family-based association analysis in 380 UK SLE nuclear families.
      Using a higher density of markers than has hitherto been screened, we show that
      there is association with two SNPs in the first intron, rs2004640 (P = 3.4 x 10(
      4)) and rs3807306 (P = 4.9 x 10(-4)), and the association extends into the 3'
      untranslated region (UTR). There is a single haplotype block encompassing IRF5
      and we show for the first time that the gene comprises two over-transmitted
      haplotypes and a single under-transmitted haplotype. The strongest association is
      with a TCTAACT haplotype (T:U = 1.92, P = 5.8 x 10(-5)), which carries all the
      over-transmitted alleles from this study. Haplotypes carrying the T alleles of
      rs2004640 and rs2280714 and the A allele of rs10954213 are over-transmitted in
      SLE families. The TAT haplotype shows a dose-dependent relationship with mRNA
      expression. A differential expression pattern was seen between two expression
      probes located each side of rs10954213 in the 3'-UTR. rs10954213 shows the
      strongest association with RNA expression levels (P = 1 x 10(-14)). The A allele
      of rs10954213 creates a functional polyadenylation site and the A genotype
      correlates with increased expression of a transcript variant containing a shorter
      3'-UTR. Expression levels of transcript variants with the shorter or longer 3'
      UTRs are inversely correlated. Our data support a new mechanism by which an IRF5
      polymorphism controls the expression of alternate transcript variants which may
      have different effects on interferon signalling.

PMID- 17189289
TI  - Human SULT1A1 gene: copy number differences and functional implications.
AB  - SULT1A1, which catalyzes the sulfate conjugation of a wide variety of natural and
      synthetic compounds, is genetically polymorphic. Biochemical and pharmacogenetic
      studies have demonstrated that individual variation in the level of enzyme
      activity is inherited. Common single-nucleotide polymorphisms (SNPs) located in
      the open reading frame and in the 5'-flanking region (5'-FR) may account for a
      portion of this individual variation. In this study, we demonstrate the presence
      of SULT1A1 gene deletions and duplications, representing an additional source of
      variability in the metabolic activity of this enzyme. A quantitative multiplex
      PCR assay was used to measure the extent of copy number differences and the
      frequency of these events in different populations. An analysis of DNA from 362
      Caucasian-American and 99 African-American showed the presence of 1 to
      approximately 5 copies of SULT1A1 in individual samples: 5% of Caucasian subjects
      contained a single copy of the gene and 26% had three or more copies, while 63%
      of African-American subjects had three or more copies. Analysis of the genomic
      region surrounding the SULT1A1 gene in three separate cases with a deletion
      demonstrated that the entire SULT1A1 gene was affected. Reporter assays,
      constructed for each of the various 5'-FR SNP haplotypes, suggest that these may
      also play a role in SULT1A1 activity. However, the variability in the level of
      enzyme activity among 23 human platelet and 267 human liver samples was best
      explained by gene copy number differences when all sources of genetic variability
      were considered (P < 0.0001). Overall, these observations have obvious
      implications for the effectiveness of SULT1A1 as a drug and hormone metabolizing
      enzyme and its potential role as a risk factor for disease.

PMID- 17189290
TI  - Wild-type huntingtin participates in protein trafficking between the Golgi and
      the extracellular space.
AB  - Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused
      by an expanded CAG trinucleotide repeat in the first exon of the HD gene, which
      results in a toxic polyglutamine stretch within huntingtin, the protein it
      encodes. Understanding the normal function of this essential protein is vital to
      understanding the root of the disease, yet despite more than a decade of
      investigation, its role in the cell remains elusive. Identifying the subcellular
      localization of huntingtin and understanding its effects on global gene
      expression are critical to this endeavor. While most reports agree that
      huntingtin is predominantly a cytoplasmic protein, conflicting distribution
      patterns have been demonstrated at the subcellular level. Here, we examine wild
      type huntingtin's localization in cultured cells by expressing the full-length
      human protein tagged with enhanced green fluorescent protein (EGFP) within its
      unspliced genomic context. In fibrosarcoma and neuroblastoma cells, huntingtin
      shows discrete punctate, perinuclear localization overlapping largely with the
      trans-Golgi and cytoplasmic clathrin-coated vesicles, implicating huntingtin in
      vesicle trafficking. To determine whether huntingtin is involved in trafficking a
      specific subset of proteins, we measured changes in global transcription levels
      in embryonic stem cells and neurons lacking huntingtin. Huntingtin null neurons
      exhibit a significant reduction in transcripts encoding proteins destined for the
      extracellular space, many of which are components of the extracellular matrix or
      involved in cellular adhesion, receptor binding and hormone activity. Together,
      these findings support a role for huntingtin in the intracellular trafficking of
      proteins required for the construction of the extracellular matrix.

PMID- 17189291
TI  - Neuronal vulnerability of CLN3 deletion to calcium-induced cytotoxicity is
      mediated by calsenilin.
AB  - Calsenilin/DREAM/KChIP3, a neuronal Ca(2+)-binding protein, has multifunctions in
      nucleus and cytosol. Here, we identified CLN3 as a calsenilin-binding partner
      whose mutation or deletion is observed in Batten disease. In vitro binding and
      immunoprecipitation assays show that calsenilin interacts with the C-terminal
      region of CLN3 and the increase of Ca(2+) concentration in vitro and in cells
      causes significant dissociation of calsenilin from CLN3. Ectopic expression of
      CLN3 or its deletion mutant containing only the C-terminus (153-438) and capable
      of binding to calsenilin suppresses thapsigargin or A23187-induced death of
      neuronal cells. In contrast, CLN3 deletion mutant containing the N-terminus (1
      153) or (1-263), which is frequently found in Batten disease, induces the
      perturbation of Ca(2+) transient and fails to inhibit the cell death. In
      addition, the expression of calsenilin is increased in the brain tissues of CLN3
      knock-out mice and SH-SY5Y/CLN3 knock-down cells. Down-regulation of CLN3
      expression sensitizes SH-SY5Y cells to thapsigargin or A23187. However,
      additional decrease of calsenilin expression rescues the sensitivity of SH
      SY5Y/CLN3 knock-down cells to Ca(2+)-mediated cell death. These results suggest
      that the vulnerability of CLN3 knock-out or CLN3 deletion (1-153)-expressing
      neuronal cells to Ca(2+)-induced cell death may be mediated by calsenilin.

PMID- 17189293
TI  - Truncated APC regulates the transcriptional activity of beta-catenin in a cell
      cycle dependent manner.
AB  - Most colon cancer cells express truncated versions of the tumour suppressor
      Adenomatous Polyposis Coli (APC). These molecules are selected during
      tumourigenesis for impaired beta-catenin degrading activity. In this study, we
      describe that truncated APC can still control the activity of beta-catenin in
      colon cancer cell lines via its first 20 amino acid repeat. First, we show that
      both endogenous and ectopically expressed truncated APC molecules can bind to
      beta-catenin. Second, reduction of the levels of truncated APC by RNA
      interference increases the activity of a beta-catenin-dependent reporter gene and
      stimulates the expression of the beta-catenin target gene AXIN2/conductin. This
      occurs without alterations of the amounts of cytosolic beta-catenin. Conversely,
      ectopic expression of truncated APC decreases beta-catenin-dependent
      transcription without affecting the intensity of immunofluorescence staining of
      beta-catenin in transfected cells. Third, we reveal that the APC level increases
      when cells reach the G1-S boundary during cell cycle progression. Simultaneously,
      the amount of beta-catenin bound to APC increases and the transcriptional
      activity of beta-catenin drops in an APC-dependent manner. Again, this occurs
      independently of the amounts of either total or phosphorylated cytosolic beta
      catenin. Together, these results indicate that truncated APC controls the ability
      of beta-catenin to activate transcription. As we also show that the inhibition
      involves the first 20 amino acid repeat of APC, our data suggest that colon
      cancer cells retain a truncated APC molecule containing at least the first 20
      amino acid repeat to modulate the transcriptional activity of beta-catenin in a
      cell cycle-dependent manner.

PMID- 17189294
TI  - The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG
      levels in women with polycystic ovary syndrome.
AB  - BACKGROUND: Hyperandrogenaemia is a common feature of polycystic ovary syndrome
      (PCOS). The sex hormone-binding globulin (SHBG) gene was proposed as being a PCOS
      candidate gene. A possible influence of the microsatellite polymorphism
      (TAAAA)(n) in the SHBG gene on serum SHBG levels in PCOS patients was
      investigated. METHODS: One hundred and twenty-three PCOS patients and 110 age
      matched controls were included in the study. Peripheral blood samples were
      obtained. Genotyping of the (TAAAA)(n) polymorphism in the SHBG gene was
      performed. Serum LH, FSH, SHBG and total testosterone concentrations were
      determined. RESULTS: SHBG alleles with 6-11 TAAAA repeats were found. None of the
      SHBG alleles or genotypes were present at a significantly more frequent rate in
      PCOS patients compared with controls. Serum SHBG levels were significantly lower
      (P < 0.001) in PCOS patients compared with controls and were found to be strongly
      influenced by the (TAAAA)(n) SHBG polymorphism, in both the PCOS (55.3%) and
      control (33.1%) groups of patients. CONCLUSIONS: The (TAAAA)(n) SHBG gene
      polymorphism might be an important predictor for serum SHBG levels and,
      consequently, for hyperandrogenaemic clinical presentation of PCOS.

PMID- 17189292
TI  - Structural variation on the short arm of the human Y chromosome: recurrent
      multigene deletions encompassing Amelogenin Y.
AB  - Structural polymorphism is increasingly recognized as a major form of human
      genome variation, and is particularly prevalent on the Y chromosome. Assay of the
      Amelogenin Y gene (AMELY) on Yp is widely used in DNA-based sex testing, and
      sometimes reveals males who have interstitial deletions. In a collection of 45
      deletion males from 12 populations, we used a combination of sequence-tagged site
      mapping, and binary-marker and Y-short tandem repeat haplotyping to understand
      the structural basis of this variation. Of the 45 deletion males, 41 carry
      indistinguishable deletions, 3.0-3.8 Mb in size. Breakpoint mapping strongly
      implicates a mechanism of non-allelic homologous recombination between the
      proximal major array of TSPY gene-containing repeats, and a single distal copy of
      TSPY; this is supported by the estimation of TSPY copy number in deleted and non
      deleted males. The remaining four males carry three distinct non-recurrent
      deletions (2.5-4.0 Mb), which may be due to non-homologous mechanisms.
      Haplotyping shows that TSPY-mediated deletions have arisen seven times
      independently in the sample. One instance, represented by 30 chromosomes mostly
      of Indian origin within haplogroup J2e1*/M241, has a time-to-most-recent-common
      ancestor of approximately 7700+/-1300 years. In addition to AMELY, deletion males
      all lack the genes PRKY and TBL1Y, and the rarer deletion classes also lack
      PCDH11Y. The persistence and expansion of deletion lineages, together with direct
      phenotypic evidence, suggests that absence of these genes has no major
      deleterious effects.

PMID- 17189295
TI  - The rise and fall of cardiac rehabilitation in the United Kingdom since 1998.
AB  - BACKGROUND: Provision of cardiac rehabilitation is inadequate in all countries in
      which it has been measured. This study assesses the provision in the United
      Kingdom and the changes between 1998 and 2004. METHODS: All UK cardiac
      rehabilitation programmes were surveyed annually. Figures for each year were up
      rated to account for missing data and compared with national data for acute
      myocardial infarction, coronary artery bypass grafting (CABG) and percutaneous
      coronary intervention (PCI). The total numbers and percentage of eligible
      patients included were charted for 7 years. RESULTS: For centres giving figures,
      the total number treated rose from 29,890 in 1998 to 37,129 in 2004. The up-rated
      figures show that the percentage of eligible patients enrolled rose from 25.0% in
      1998 to 31.5% in 1999 and has changed little since, falling from 31.3% in 2002 to
      28.5% in 2004. About 25% of myocardial infarction patients, 75% of CABG patients
      and 20% of PCI patients joined cardiac rehabilitation programmes. CONCLUSIONS:
      The National Service Framework for Coronary Heart Disease set a target for 85% of
      myocardial infarct and coronary revascularization patients to be enrolled in
      rehabilitation programmes. Only one-third of this number is currently being
      enrolled and the percentage is falling.

PMID- 17189296
TI  - The discovery of transcriptional modules by a two-stage matrix decomposition
      approach.
AB  - MOTIVATION: We address the problem of identifying gene transcriptional modules
      from gene expression data by proposing a new approach. Genes mostly interact with
      each other to form transcriptional modules for context-specific cellular
      activities or functions. Unraveling such transcriptional modules is important for
      understanding biological network, deciphering regulatory mechanisms and
      identifying biomarkers. METHOD: The proposed algorithm is based on two-stage
      matrix decomposition. We first model microarray data as non-linear mixtures and
      adopt the non-linear independent component analysis to reduce the non-linear
      distortion and separate the data into independent latent components. We then
      apply the probabilistic sparse matrix decomposition approach to model the
      'hidden' expression profiles of genes across the independent latent components as
      linear weighted combinations of a small number of transcriptional regulator
      profiles. Finally, we propose a general scheme for identifying gene modules from
      the outcomes of the matrix decomposition. RESULTS: The proposed algorithm
      partitions genes into non-mutually exclusive transcriptional modules, independent
      from expression profile similarity measurement. The modules contain genes with
      not only similar but different expression patterns, and show the highest
      enrichment of biological functions in comparison with those by other methods. The
      usefulness of the algorithm was validated by a yeast microarray data analysis.
      AVAILABILITY: The software is available upon request to the authors.

PMID- 17189297
TI  - Anatomy of Escherichia coli sigma70 promoters.
AB  - Information theory was used to build a promoter model that accounts for the -10,
      the -35 and the uncertainty of the gap between them on a common scale. Helical
      face assignment indicated that base -7, rather than -11, of the -10 may be
      flipping to initiate transcription. We found that the sequence conservation of
      sigma70 binding sites is 6.5 +/- 0.1 bits. Some promoters lack a -35 region, but
      have a 6.7 +/- 0.2 bit extended -10, almost the same information as the bipartite
      promoter. These results and similarities between the contacts in the extended -10
      binding and the -35 suggest that the flexible bipartite sigma factor evolved from
      a simpler polymerase. Binding predicted by the bipartite model is enriched around
      35 bases upstream of the translational start. This distance is the smallest 5'
      mRNA leader necessary for ribosome binding, suggesting that selective pressure
      minimizes transcript length. The promoter model was combined with models of the
      transcription factors Fur and Lrp to locate new promoters, to quantify promoter
      strengths, and to predict activation and repression. Finally, the DNA-bending
      proteins Fis, H-NS and IHF frequently have sites within one DNA persistence
      length from the -35, so bending allows distal activators to reach the polymerase.

PMID- 17189300
TI  - Paraneoplastic cerebellar degeneration and anti-Yo antibodies in a man with
      prostatic adenocarcinoma.

PMID- 17189298
TI  - The BRCT domain of mammalian Pes1 is crucial for nucleolar localization and rRNA
      processing.
AB  - The nucleolar protein Pes1 interacts with Bop1 and WDR12 in a stable complex
      (PeBoW-complex) and its expression is tightly associated with cell proliferation.
      The yeast homologue Nop7p (Yph1p) functions in both, rRNA processing and cell
      cycle progression. The presence of a BRCT-domain (BRCA1 C-terminal) within Pes1
      is quite unique for an rRNA processing factor, as this domain is normally found
      in factors involved in DNA-damage or repair pathways. Thus, the function of the
      BRCT-domain in Pes1 remains elusive. We established a conditional siRNA-based
      knock-down-knock-in system and analysed a panel of Pes1 truncation mutants for
      their functionality in ribosome synthesis in the absence of endogenous Pes1.
      Deletion of the BRCT-domain or single point mutations of highly conserved
      residues caused diffuse nucleoplasmic distribution and failure to replace
      endogenous Pes1 in rRNA processing. Further, the BRCT-mutants of Pes1 were less
      stable and not incorporated into the PeBoW-complex. Hence, the integrity of the
      BRCT-domain of Pes1 is crucial for nucleolar localization and its function in
      rRNA processing.

PMID- 17189299
TI  - Neurological control of human sexual behaviour: insights from lesion studies.
AB  - We review the human literature examining the effects of neurological insult on
      human sexual behaviour. We provide a synthesis of the findings to date, and
      identify key brain regions associated with specific aspects of human sexual
      behaviour. These include subcortical and cortical regions, with the mesial
      temporal lobe and the amygdala in particular being a crucial structure in the
      mediation of human sexual drive.

PMID- 17189301
TI  - What do patients think about appearing in neurology "grand rounds"?

PMID- 17189302
TI  - Cerebral venous thrombosis and plasma concentrations of factor VIII and von
      Willebrand factor: a case control study.
AB  - BACKGROUND: High plasma concentrations of factor VIII (FVIII) and von Willebrand
      factor (VWF) have been recently associated with a moderately increased risk of
      venous thrombosis, but their roles in cerebral sinus and venous thrombosis (CSVT)
      have not been addressed. To determine whether elevation of FVIII and VWF is more
      frequent in CSVT, we analysed plasma levels of FVIII and VWF in a case control
      study. METHODS: The study population consisted of 25 consecutive patients (of
      whom nine were excluded) admitted for CSVT to the Department of Neurology, Amiens
      University Hospital, France, from January 1997 to December 2002, for a general
      screening for thrombophilia. Sixty-four healthy subjects matched for age and sex
      formed the group control. RESULTS: Mean FVIII (CSVT: 167.3 (SD 48.8) IU/dl;
      control group: 117.9 (39.8) IU/dl; p = 0.001) and VWF levels (CSVT: 165.4
      (76.5)%; control group: 108.5 (27.8)%; p = 0.01) were significantly higher in the
      CSVT group. Using the 95th percentile of the control group as the cut off value,
      elevated FVIII (>190 IU/dl) occurred in 25% (4/16) (p = 0.005) and elevated VWF
      (>168%) in 37.5% (6/16) of patients with CSVT (p<0.001). Using previously
      reported cut off values (>150 IU/dl or >150%) showed the same results (FVIII: p =
      0.005; VWF: p = 0.009). CONCLUSION: Our study suggests that elevation of plasma
      factor VIII levels is the most common prothrombotic risk factor for CSVT.
      Elevation of VWF is also associated with an increased risk of CSVT but its effect
      seems to be partly mediated through FVIII.

PMID- 17189303
TI  - Photophysics and photochemistry of horseradish peroxidase A2 upon ultraviolet
      illumination.
AB  - Detailed analysis of the effects of ultraviolet (UV) and blue light illumination
      of horseradish peroxidase A2, a heme-containing enzyme that reduces H(2)O(2) to
      oxidize organic and inorganic compounds, is presented. The effects of increasing
      illumination time on the protein's enzymatic activity, Reinheitzahl value,
      fluorescence emission, fluorescence lifetime distribution, fluorescence mean
      lifetime, and heme absorption are reported. UV illumination leads to an
      exponential decay of the enzyme activity followed by changes in heme group
      absorption. Longer UV illumination time leads to lower T(m) values as well as
      helical content loss. Prolonged UV illumination and heme irradiation at 403 nm
      has a pronounced effect on the fluorescence quantum yield correlated with changes
      in the prosthetic group pocket, leading to a pronounced decrease in the heme's
      Soret absorbance band. Analysis of the picosecond-resolved fluorescence emission
      of horseradish peroxidase A2 with streak camera shows that UV illumination
      induces an exponential change in the preexponential factors distribution
      associated to the protein's fluorescence lifetimes, leading to an exponential
      increase of the mean fluorescence lifetime. Illumination of aromatic residues and
      of the heme group leads to changes indicative of heme leaving the molecule and/or
      that photoinduced chemical changes occur in the heme moiety. Our studies bring
      new insight into light-induced reactions in proteins. We show how streak camera
      technology can be of outstanding value to follow such ultrafast processes and how
      streak camera data can be correlated with protein structural changes.

PMID- 17189304
TI  - Irreducible representation for nucleotide sequence physical properties and self
      consistency of nearest-neighbor dimer sets.
AB  - A compact representation of usual DNA/RNA four-nucleotide sets based on molecular
      affinity classes is proposed. In a geometrical correspondence to this
      formulation, it follows that intrinsic tetrahedral symmetry correlates nucleotide
      properties. This representation also leads to a proper decomposition frame for
      any sequence-dependent physical expectation. Thermodynamic and other physical
      properties of nucleotide sequences are most often stated within the scope of
      nearest-neighbor models and decomposed in terms of dimer properties. The inverse
      problem of obtaining dimer set properties is, however, well known to be ill-posed
      due to sequence composition closure relations. Analysis of the dimer set
      composition and structure within the novel tetrahedral formulation provides
      important self-consistency relations, solving the ill posed nature of the
      original formulation. As an applied example, we analyze DNA oligomer duplex free
      energy data available on the literature. It is shown that imposition of stringent
      self-consistency relations does not decrease fit quality to the experimental data
      set. On the other hand, an improved dimer set with physically consistent free
      energies is obtained. Meaningful corrections to previous determinations are found
      when the self-consistent set is applied to calculate free energies for sequences
      with composition order bias.

PMID- 17189305
TI  - Single giant vesicle rupture events reveal multiple mechanisms of glass-supported
      bilayer formation.
AB  - The formation of supported lipid bilayers (SLBs) on glass from giant unilamellar
      vesicles (GUVs) was studied using fluorescence microscopy. We show that GUV
      rupture occurs by at least four mechanisms, including 1), spontaneous rupture of
      isolated GUVs yielding almost heart-shaped bilayer patches (asymmetric rupture);
      2), spontaneous rupture of isolated GUVs yielding circular bilayer patches
      (symmetric rupture); 3), induced rupture of an incoming vesicle when it contacts
      a planar bilayer edge; and 4), induced rupture of an adsorbed GUV when a nearby
      GUV spontaneously ruptures. In pathway 1, the dominant rupture pathway for
      isolated GUVs, GUVs deformed upon adsorption to the glass surface, and planar
      bilayer patch formation was initiated by rupture pore formation near the rim of
      the glass-bilayer interface. Expanding rupture pores led to planar bilayer
      formation in approximately 10-20 ms. Rupture probability per unit time depended
      on the average intrinsic curvature of the component lipids. The membrane leaflet
      adsorbed to the glass surface in planar bilayer patches originated from the outer
      leaflet of GUVs. Pathway 2 was rarely observed. We surmise that SLB formation is
      predominantly initiated by pathway 1 rupture events, and that rupture events
      occurring by pathways 3 and 4 dominate during later stages of SLB formation.

PMID- 17189306
TI  - Correlation spectroscopy of minor fluorescent species: signal purification and
      distribution analysis.
AB  - We are performing experiments that use fluorescence resonance energy transfer
      (FRET) and fluorescence correlation spectroscopy (FCS) to monitor the movement of
      an individual donor-labeled sliding clamp protein molecule along acceptor-labeled
      DNA. In addition to the FRET signal sought from the sliding clamp-DNA complexes,
      the detection channel for FRET contains undesirable signal from free sliding
      clamp and free DNA. When multiple fluorescent species contribute to a correlation
      signal, it is difficult or impossible to distinguish between contributions from
      individual species. As a remedy, we introduce "purified FCS", which uses single
      molecule burst analysis to select a species of interest and extract the
      correlation signal for further analysis. We show that by expanding the
      correlation region around a burst, the correlated signal is retained and the
      functional forms of FCS fitting equations remain valid. We demonstrate the use of
      purified FCS in experiments with DNA sliding clamps. We also introduce "single
      molecule FCS", which obtains diffusion time estimates for each burst using
      expanded correlation regions. By monitoring the detachment of weakly-bound 30-mer
      DNA oligomers from a single-stranded DNA plasmid, we show that single-molecule
      FCS can distinguish between bursts from species that differ by a factor of 5 in
      diffusion constant.

PMID- 17189308
TI  - Kinetics of P2X7 receptor-operated single channels currents.
AB  - Human P2X7 receptors were expressed in Xenopus laevis oocytes and single channels
      were recorded using the patch-clamp technique in the outside-out configuration.
      ATP4- evoked two types of P2X7 receptor-mediated single channel currents
      characterized by short-lived and long-lived openings. The short- and long-lasting
      open states had mean open times of approximately 5 and approximately 20 ms and
      slope conductances near -60 mV of 9 and 13 pS, respectively. The open
      probabilities of the short and long openings were strongly [ATP4-]-dependent with
      EC50 values of approximately 0.3 mM and approximately 0.1 mM ATP4-, respectively.
      The channel kinetics did not change significantly during sustained P2X7 receptor
      activation for several minutes, as was also observed in recordings in the cell
      attached patch-clamp configuration. Activation and deactivation of the short
      openings followed exponential time courses with time constants in the range of 20
      ms, and displayed a shallow [ATP4-] dependence of the activation process. The
      kinetics of the short channel openings at negative membrane potentials fitted
      well to a linear C-C-C-O model with two ATP4- binding steps at equal binding
      sites with a dissociation constant Kd of 139 microM.

PMID- 17189309
TI  - Natural fluctuations of an electropore show fractional Levy stable motion.
AB  - Until now a stable long-lived electronanopore could be generated in a lipid
      membrane only under current-clamp conditions, and stochastic properties of a
      single nanopore have been studied by the chronopotentiometry. The current-clamp
      experiment introduces negative feedback, which could be responsible for the
      electropore fluctuations and observed 1/fB power spectrum. A new electroporation
      method, chronoamperometry after current clamp (CACC), prevents irreversible
      rupture of the membrane and eliminates the feedback by clamping the voltage after
      previous electroporation. The experiments show that the electropore size can also
      be stabilized under constant potential. The electropore fluctuations do not need
      feedback to appear. The fluctuations are self-similar with a short memory. CACC
      provides an effective tool for studying the natural dynamics of an electropore in
      various environments, which was tested with Na+ and Al3+ ions. Comparison between
      chronopotentiometry and CACC reveals that the feedback mainly shortens the memory
      of the stochastic fluctuations. Statistical analysis shows that the conductance
      fluctuations can be approximately modeled as a fractional Levy stable motion for
      a small hydrophilic electropore, which tends to fractional Brownian motion when
      the electropore increases its size. A hypothesis is presented that this
      transition reflects a more regular shape of big nanopores.

PMID- 17189310
TI  - Measuring cell forces by a photoelastic method.
AB  - A new method for measuring the mechanical forces exerted by cells on the
      substratum and through the substratum to act on other cells is described. This
      method depends upon the growth of cells on a photoelastic substratum,
      polydimethylsiloxane coated with a near monolayer of fibronectin. Changes in the
      forces applied by the cells to the substratum lead to changes in birefringence,
      which can be measured and recorded by the Polscope computer-controlled polarizing
      microscope. The changes in azimuth and retardance can be measured. A method for
      calibrating the stress is described. The method is sensitive down to forces of 1
      pN per square microns. Fairly rapid changes with time can be recorded with a time
      resolution of approximately 1 s. The observations show that both isolated
      adhering, spread cells and also cells close to contact exert stresses on the
      substratum and that the stresses are those that would be produced by forces of 10
      1000 pN per cell. The forces are almost certainly exerted on nearby cells since
      movement of one cell causes strains to appear around other nearby cells. The
      method has the defect that strains under the cells, though detectable in
      principle, are unclear due to birefringence of the components of the cytoplasm
      and nucleus. It is of special interest that the strains on the substratum can
      change in the time course of a few seconds and appear to be concentrated near the
      base of the lamellopodium of the cell as though they originated there. As well as
      exerting forces on the substratum in the direction of the long axis of the cell,
      appreciable forces are exerted from the lateral sides of the cell. The
      observations and measurements tend to argue that microtopography and embedded
      beads can concentrate the forces.

PMID- 17189307
TI  - Subunit dependence of Na channel slow inactivation and open channel block in
      cerebellar neurons.
AB  - Purkinje and cerebellar nuclear neurons both have Na currents with resurgent
      kinetics. Previous observations, however, suggest that their Na channels differ
      in their susceptibility to entering long-lived inactivated states. To compare
      fast inactivation, slow inactivation, and open-channel block, we recorded voltage
      clamped, tetrodotoxin-sensitive Na currents in Purkinje and nuclear neurons
      acutely isolated from mouse cerebellum. In nuclear neurons, recovery from all
      inactivated states was slower, and open-channel unblock was less voltage
      dependent than in Purkinje cells. To test whether specific subunits contributed
      to this differential stability of inactivation, experiments were repeated in
      Na(V)1.6-null (med) mice. In med Purkinje cells, recovery times were prolonged
      and the voltage dependence of open-channel block was reduced relative to control
      cells, suggesting that availability of Na(V)1.6 is quickly restored at negative
      potentials. In med nuclear cells, however, currents were unchanged, suggesting
      that Na(V)1.6 contributes little to wild-type nuclear cells. Extracellular Na(+)
      prevented slow inactivation more effectively in Purkinje than in nuclear neurons,
      consistent with a resilience of Na(V)1.6 to slow inactivation. The tendency of
      nuclear Na channels to inactivate produced a low availability during trains of
      spike-like depolarization. Hyperpolarizations that approximated synaptic
      inhibition effectively recovered channels, suggesting that increases in Na
      channel availability promote rebound firing after inhibition.

PMID- 17189311
TI  - Spontaneous creation of macroscopic flow and metachronal waves in an array of
      cilia.
AB  - Cells carrying cilia on their surface show many striking features: alignment of
      cilia in an array, two-phase asymmetric beating for each cilium, and existence of
      metachronal coordination with a constant phase difference between two adjacent
      cilia. We give simple theoretical arguments based on hydrodynamic coupling and an
      internal mechanism of the cilium derived from the behavior of a collection of
      molecular motors to account qualitatively for these cooperative features.
      Hydrodynamic interactions can lead to the alignment of an array of cilia. We
      study the effect of a transverse external flow and obtain a two-phase
      asymmetrical beating, faster along the flow and slower against the flow,
      proceeding around an average curved position. We show that an aligned array of
      cilia is able to spontaneously break the left-right symmetry and to create a
      global average flow. Metachronal coordination arises as a consequence of the
      internal mechanism of the cilia and their hydrodynamic couplings, with a
      wavelength comparable to that found in experiments. It allows the cilia to start
      beating at a lower adenosine-triphosphate threshold and at a higher frequency
      than for a single cilium. It also leads to a rather stationary flow, which might
      be its major advantage.

PMID- 17189312
TI  - Sources of anomalous diffusion on cell membranes: a Monte Carlo study.
AB  - A stochastic random walk model of protein molecule diffusion on a cell membrane
      was used to investigate the fundamental causes of anomalous diffusion in two
      dimensional biological media. Three different interactions were considered:
      collisions with fixed obstacles, picket fence posts, and capture by, or exclusion
      from, lipid rafts. If motion is impeded by randomly placed, fixed obstacles, we
      find that diffusion can be highly anomalous, in agreement with previous studies.
      In contrast, collision with picket fence posts has a negligible effect on the
      anomalous exponent at realistic picket fence parameters. The effects of lipid
      rafts are more complex. If proteins partition into lipid rafts there is a small
      to moderate effect on the anomalous exponent, whereas if proteins are excluded
      from rafts there is a large effect on the anomalous exponent. In combination,
      these mechanisms can explain the level of anomaly in experimentally observed
      membrane diffusion, suggesting that anomalous diffusion is caused by multiple
      mechanisms whose effects are approximately additive. Finally, we show that the
      long-range diffusion rate, D(macro), estimated from fluorescence recovery after
      photobleaching studies, can be much smaller than D(micro), the small-scale
      diffusion rate, and is highly sensitive to obstacle densities and other impeding
      structures.

PMID- 17189313
TI  - Laser-induced transient grating analysis of dynamics of interaction between
      sensory rhodopsin II D75N and the HtrII transducer.
AB  - The interaction between sensory rhodopsin II (SRII) and its transducer HtrII was
      studied by the time-resolved laser-induced transient grating method using the
      D75N mutant of SRII, which exhibits minimal visible light absorption changes
      during its photocycle, but mediates normal phototaxis responses. Flash-induced
      transient absorption spectra of transducer-free D75N and D75N joined to 120 amino
      acid residues of the N-terminal part of the SRII transducer protein HtrII
      (DeltaHtrII) showed only one spectrally distinct K-like intermediate in their
      photocycles, but the transient grating method resolved four intermediates (K(1)
      K(4)) distinct in their volumes. D75N bound to HtrII exhibited one additional
      slower kinetic species, which persists after complete recovery of the initial
      state as assessed by absorption changes in the UV-visible region. The kinetics
      indicate a conformationally changed form of the transducer portion (designated
      Tr*), which persists after the photoreceptor returns to the unphotolyzed state.
      The largest conformational change in the DeltaHtrII portion was found to cause a
      DeltaHtrII-dependent increase in volume rising in 8 micros in the K(4) state and
      a drastic decrease in the diffusion coefficient (D) of K(4) relatively to those
      of the unphotolyzed state and Tr*. The magnitude of the decrease in D indicates a
      large structural change, presumably in the solvent-exposed HAMP domain of
      DeltaHtrII, where rearrangement of interacting molecules in the solvent would
      substantially change friction between the protein and the solvent.

PMID- 17189314
TI  - Protein stability in ice.
AB  - This study presents an experimental approach, based on the change of Trp
      fluorescence between native and denatured states of proteins, which permits to
      monitor unfolding equilibria and the thermodynamic stability (DeltaG degrees ) of
      these macromolecules in frozen aqueous solutions. The results obtained by
      guanidinium chloride denaturation of the azurin mutant C112S from Pseudomonas
      aeruginosa, in the temperature range from -8 to -16 degrees C, demonstrate that
      the stability of the native fold may be significantly perturbed in ice depending
      mainly on the size of the liquid water pool (V(L)) in equilibrium with the solid
      phase. The data establish a threshold, around V(L)=1.5%, below which in ice
      DeltaG degrees decreases progressively relative to liquid state, up to 3
      kcal/mole for V(L)=0.285%. The sharp dependence of DeltaG degrees on V(L) is
      consistent with a mechanism based on adsorption of the protein to the ice
      surface. The reduction in DeltaG degrees is accompanied by a corresponding
      decrease in m-value indicating that protein-ice interactions increase the solvent
      accessible surface area of the native fold or reduce that of the denatured state,
      or both. The method opens the possibility for examining in a more quantitative
      fashion the influence of various experimental conditions on the ice perturbation
      and in particular to test the effectiveness of numerous additives used in
      formulations to preserve labile pharmaco proteins.

PMID- 17189316
TI  - Protein-protein association in polymer solutions: from dilute to semidilute to
      concentrated.
AB  - In a typical cell, proteins function in the crowded cytoplasmic environment where
      30% of the space is occupied by macromolecules of varying size and nature. This
      environment may be simulated in vitro using synthetic polymers. Here, we followed
      the association and diffusion rates of TEM1-beta-lactamase (TEM) and the beta
      lactamase inhibitor protein (BLIP) in the presence of crowding agents of varying
      molecular mass, from monomers (ethylene glycol, glycerol, or sucrose) to
      polymeric agents such as different polyethylene glycols (PEGs, 0.2-8 kDa) and
      Ficoll. An inverse linear relation was found between translational diffusion of
      the proteins and viscosity in all solutions tested, in accordance with the Stokes
      Einstein (SE) relation. Conversely, no simple relation was found between either
      rotational diffusion rates or association rates (k(on)) and viscosity. To assess
      the translational diffusion-independent steps along the association pathway, we
      introduced a new factor, alpha, which corrects the relative change in k(on) by
      the relative change in solution viscosity, thus measuring the deviations of the
      association rates from SE behavior. We found that these deviations were related
      to the three regimes of polymer solutions: dilute, semidilute, and concentrated.
      In the dilute regime PEGs interfere with TEM-BLIP association by introducing a
      repulsive force due to solvophobic preferential hydration, which results in
      slower association than predicted by the SE relation. Crossing over from the
      dilute to the semidilute regime results in positive deviations from SE behavior,
      i.e., relatively faster association rates. These can be attributed to the
      depletion interaction, which results in an effective attraction between the two
      proteins, winning over the repulsive force. In the concentrated regime, PEGs
      again dramatically slow down the association between TEM and BLIP, an effect that
      does not depend on the physical dimensions of PEGs, but rather on their mass
      concentration. This is probably a manifestation of the monomer-like repulsive
      depletion effect known to occur in concentrated polymer solutions. As a
      transition from moderate to high crowding agent concentration can occur in the
      cellular milieu, this behavior may modulate protein association in vivo, thereby
      modulating biological function.

PMID- 17189315
TI  - Gating properties of heterotypic gap junction channels formed of connexins 40,
      43, and 45.
AB  - Connexins (Cxs) 40, 43, and 45 are expressed in many different tissues, but most
      abundantly in the heart, blood vessels, and the nervous system. We examined
      formation and gating properties of heterotypic gap junction (GJ) channels
      assembled between cells expressing wild-type Cx40, Cx43, or Cx45 and their fusion
      forms tagged with color variants of green fluorescent protein. We show that these
      Cxs, with exception of Cxs 40 and 43, are compatible to form functional
      heterotypic GJ channels. Cx40 and Cx43 hemichannels are unable or effectively
      impaired in their ability to dock and/or assemble into junctional plaques. When
      cells expressing Cx45 contacted those expressing Cx40 or Cx43 they readily formed
      junctional plaques with cell-cell coupling characterized by asymmetric junctional
      conductance dependence on transjunctional voltage, V(j). Cx40/Cx45 heterotypic GJ
      channels preferentially exhibit V(j)-dependent gating transitions between open
      and residual states with a conductance of approximately 42 pS; transitions
      between fully open and closed states with conductance of approximately 52 pS in
      magnitude occur at substantially lower ( approximately 10-fold) frequency.
      Cx40/Cx45 junctions demonstrate electrical signal transfer asymmetry that can be
      modulated between unidirectional and bidirectional by small changes in the
      difference between holding potentials of the coupled cells. Furthermore, both
      fast and slow gating mechanisms of Cx40 exhibit a negative gating polarity.

PMID- 17189318
TI  - Genetic evidence for a protective role of heat shock factor 1 against irritant
      induced gastric lesions.
AB  - Gastric lesions result from an imbalance between aggressive and defensive
      factors. Indirect lines of evidence suggest that heat shock proteins (HSPs)
      induced by various aggressive factors provide a major protective mechanism. In
      this study, we compared gastric ulcerogenic response in wild-type mice and in
      those lacking heat shock factor 1 (HSF1), a transcription factor for hsp genes.
      The severity of gastric lesions induced by ethanol or hydrochloric acid was
      worsened in HSF1-null mice. Immunoblotting, real-time reverse transcription
      polymerase chain reaction, immunohistochemical analysis, and terminal
      deoxynucleotidyl transferase dUTP nick-end labeling assay revealed that the
      ethanol administration up-regulated gastric mucosal HSPs, in particular HSP70, in
      an HSF1-dependent manner, and more apoptotic cells were observed in the gastric
      mucosa of HSF1-null mice than in wild-type mice. In contrast, other parameters
      governing the gastric ulcerogenic response, including gastric acid secretion,
      gastric mucosal blood flow, and prostaglandin E(2) levels, were not significantly
      affected by the absence of the hsf1 gene. Geranylgeranylacetone (GGA), a
      clinically used antiulcer drug with HSP-inducing activity, suppressed ethanol
      induced gastric lesions in wild-type mice but not in heat shock factor 1 (HSF1)
      null mice. The results suggest that the aggravation of irritant-induced gastric
      lesions in HSF1-null mice is due to their inability to up-regulate HSPs, leading
      to apoptosis. It is also suggested that the HSP-inducing activity of GGA
      contributes to the drug's antiulcer activity. This study provides direct genetic
      evidence that HSPs, after their HSF1-dependent up-regulation, confer gastric
      protection against the irritant-induced lesions.

PMID- 17189317
TI  - A cell-semiconductor synapse: transistor recording of vesicle release in
      chromaffin cells.
AB  - The release of dense-core vesicles in bovine chromaffin cells is a model for the
      presynaptic process in neurons. It is usually studied by microamperometry of
      catecholamines with carbon fibers. Here we introduce transistor recording as a
      tool to study vesicle release. When we stimulate a chromaffin cell placed on a
      field-effect transistor, the gate voltage exhibits peaks that correlate with a
      simultaneously performed amperometric recording. We attribute the transistor
      signal to a release of protons from the extruded matrix of vesicles that lowers
      the extracellular pH and changes the electrical surface potential of the gate
      oxide. The rise time of the transistor signals is similar to that of amperometric
      responses, whereas their duration is distinctly longer. In a model computation,
      the rise time is identified with the extrusion of vesicle matrix into the narrow
      extracellular space between cell and gate oxide, and the decay time is attributed
      to pH equilibration through slow diffusion in the extruded matrix. Because the
      transistor recording relies on protons, it can be applied to acidic vesicles with
      electrochemically inactive hormones or transmitters.

PMID- 17189319
TI  - Collagen I and thrombin activate MMP-2 by MMP-14-dependent and -independent
      pathways: implications for airway smooth muscle migration.
AB  - Increased proinflammatory mediators and ECM deposition are key features of the
      airways in asthma. Matrix metalloproteinases (MMPs) are produced by airway smooth
      muscle (ASM) cells and have multiple roles in inflammation and tissue remodeling.
      We hypothesized that components of the asthmatic airway would stimulate MMP
      production and activation by ASM and contribute to airway remodeling. We measured
      human ASM-derived MMP mRNA, protein, and activity by real-time RT-PCR,
      zymography, Western blotting, and MMP activity assay. Collagen I and thrombin
      caused a synergistic increase in MMP-2 protein and total MMP activity but
      paradoxically decreased MMP-2 mRNA. Additionally, collagen I activated MMP-2 in
      culture supernatants independent of the cell surface. Together, collagen I and
      thrombin strongly enhanced MMP-14 mRNA and protein but had no effect
      individually, suggesting increased MMP-14, the activating protease for MMP-2, may
      be partially responsible for MMP-2 activation. Furthermore, collagen I reduced
      tissue inhibitor of metalloproteinase-2 protein (TIMP-2). We examined the role of
      MMPs in functions of ASM related to airway remodeling and found migration and
      proliferation were MMP dependent, whereas adhesion and apoptosis were not.
      Ilomastat inhibited migration by 25%, which was also inhibited by TIMPs 1-4 and
      increased by the MMP-2 activator thrombin. These in vitro findings suggest that
      the environment within the airways of patients with asthma enhances MMP-2 and -14
      protein and activity by a complex interaction of transcriptional and
      posttranscriptional mechanisms, which may contribute to ASM migration.

PMID- 17189320
TI  - IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle
      cells.
AB  - Recent studies into the pathogenesis of airway disorders such as asthma have
      revealed a dynamic role for airway smooth muscle cells in the perpetuation of
      airway inflammation via secretion of cytokines and chemokines. In this study, we
      evaluated whether IL-17 could enhance IL-1beta-mediated CXCL-8 release from human
      airway smooth muscle cells (HASMC) and investigated the upstream and downstream
      signaling events regulating the induction of CXCL-8. CXCL-8 mRNA and protein
      induction were assessed by real-time RT-PCR and ELISA from primary HASMC
      cultures. HASMC transfected with site-mutated activator protein (AP)-1/NF-kappaB
      CXCL-8 promoter constructs were treated with selective p38, MEK1/2, and
      phosphatidylinositol 3-kinase (PI3K) inhibitors to determine the importance of
      MAPK and PI3K signaling pathways as well as AP-1 and NF-kappaB promoter binding
      sites. We demonstrate IL-17 induced and synergized with IL-1beta to upregulate
      CXCL-8 mRNA and protein levels. Erk1/2 and p38 modulated IL-17 and IL-1beta CXCL
      8 promoter activity; however, IL-1beta also activated the PI3K pathway. The
      synergistic response mediating CXCL-8 promoter activity was dependent on both
      MAPK and PI3K signal transduction pathways and required the cooperation of AP-1
      and NF-kappaB cis-acting elements upstream of the CXCL-8 gene. Collectively, our
      observations indicate MAPK and PI3K pathways regulate the synergy of IL-17 and IL
      1beta to enhance CXCL-8 promoter activity, mRNA induction, and protein synthesis
      in HASMC via the cooperative activation of AP-1 and NF-kappaB trans-acting
      elements.

PMID- 17189321
TI  - Rosiglitazone attenuates hypoxia-induced pulmonary arterial remodeling.
AB  - Thiazolidinediones (TZDs) are insulin-sensitizing agents that also decrease
      systemic blood pressure, attenuate the formation of atherosclerotic lesions, and
      block remodeling of injured arterial walls. Recently, TZDs were shown to prevent
      pulmonary arterial (PA) remodeling in rats treated with monocrotaline. Presently
      we report studies testing the ability of the TZD rosiglitazone (ROSI) to
      attenuate pathological arterial remodeling in the lung and prevent the
      development of pulmonary hypertension (PH) in rats subjected to chronic hypoxia.
      PA remodeling was reduced in ROSI-treated animals exposed to hypoxia compared
      with animals exposed to hypoxia alone. ROSI treatment blocked muscularization of
      distal pulmonary arterioles and reversed remodeling and neomuscularization in
      lungs of animals previously exposed to chronic hypoxia. Decreased PA remodeling
      in ROSI-treated animals was associated with decreased smooth muscle cell
      proliferation, decreased collagen and elastin deposition, and increased matrix
      metalloproteinase-2 activity in the PA wall. Cells expressing the c-Kit cell
      surface marker were observed in the PA adventitia of untreated animals exposed to
      hypoxia but not in ROSI-treated hypoxic rats. Right ventricular hypertrophy and
      cardiomyocyte hypertrophy were also blunted in ROSI-treated hypoxic animals.
      Interestingly, mean PA pressures were elevated equally in the untreated and ROSI
      treated groups, indicating that ROSI had no effect on the development of PH.
      However, mean PA pressure was normalized acutely in both groups of hypoxia
      exposed animals by Fasudil, an agent that inhibits RhoA/Rho kinase-mediated
      vasoconstriction. We conclude that ROSI can attenuate and reverse PA remodeling
      and neomuscularization associated with hypoxic PH. However, this agent fails to
      block the development of PH, apparently because of its inability to repress
      sustained Rho kinase-mediated arterial vasoconstriction.

PMID- 17189322
TI  - Pulmonary artery smooth muscle cells from normal subjects and IPAH patients show
      divergent cAMP-mediated effects on TRPC expression and capacitative Ca2+ entry.
AB  - Pulmonary vascular remodeling due to overgrowth of pulmonary artery smooth muscle
      cells (PASMC) is a major cause for the elevated vascular resistance in patients
      with idiopathic pulmonary arterial hypertension (IPAH). Increased cytosolic
      Ca(2+) concentration, resulting from enhanced capacitative Ca(2+) entry (CCE) and
      upregulated transient receptor potential (TRP) channel expression, is involved in
      stimulating PASMC proliferation. The current study was designed to determine the
      impact of cAMP, a second messenger that we hypothesized would blunt aspects of
      PASMC activity, as a possible contributor to IPAH pathophysiology. Short-term (30
      min) pretreatment with forskolin (FSK; 10 muM), a direct activator of adenylyl
      cyclase, in combination with the cyclic nucleotide phosphodiesterase inhibitor
      isobutylmethylxanthine (IBMX; 200 muM), attenuated CCE in PASMC from normal
      subjects, patients without pulmonary hypertension (NPH), and patients with IPAH.
      The FSK-mediated CCE inhibition was independent of protein kinase A (PKA),
      because the PKA inhibitor H89 negligibly affected the decrease in CCE produced by
      cAMP. By contrast, longer (4 h) treatment with FSK (with IBMX) attenuated CCE in
      normal and NPH PASMC but enhanced CCE in IPAH PASMC. This enhancement of CCE was
      abolished by PKA inhibition and associated with an upregulation of TRPC3. In
      addition, cAMP increased TRPC1 mRNA expression in IPAH (but not in normal or NPH)
      PASMC, an effect blunted by H89. Furthermore, iloprost, a prostacyclin analog
      that increases cAMP, downregulated TRPC3 expression in IPAH PASMC and FSK
      mediated cAMP increase inhibited IPAH PASMC proliferation. Although a rapid rise
      in cellular cAMP decreases CCE by a PKA-independent mechanism, sustained cAMP
      increase inhibits CCE in normal and NPH PASMC but increases CCE via a PKA
      dependent pathway in IPAH PASMC. The divergent effect of cAMP on CCE parallels
      effects on TRPC expression. The results suggest that the combined use of a PKA
      inhibitor and cAMP-elevating drugs may provide a novel approach for treatment of
      IPAH.

PMID- 17189323
TI  - Nitric oxide production in the ventilatory muscles in response to acute resistive
      loading.
AB  - The effect of muscle activation on muscle nitric oxide (NO) production remains
      controversial. Whereas NO release increases in in vitro activated muscles and in
      vivo limb muscles, diaphragmatic NO synthase (NOS) activity declines after 3 h of
      inspiratory resistive loading (IRL). We tested in this study the hypotheses that
      acute IRL decreases diaphragmatic NO derivatives levels and reduces protein
      expression of neuronal (nNOS), endothelial (eNOS), and inducible (iNOS) NO
      synthases, as well as 3-nitrotyrosine formation. Anesthetized, tracheostomized,
      spontaneously breathing adult rats were subjected to IRL (50% of the maximum
      inspiratory pressure) for 1, 3, or 6 h. Quietly breathing rats served as
      controls. After 3 h of IRL, muscle eNOS and nNOS protein levels rose by 80 and
      60% of control values, respectively. Whereas eNOS expression did not change any
      further, nNOS expression reached 550% of control values after 6 h of IRL. Strong
      iNOS protein expression was detected in the diaphragms after 6 h of IRL. Total NO
      derivatives levels in the diaphragm declined during IRL as a result of reduction
      in nitrate, nitrite, and nitrosothiols. Diaphragmatic protein tyrosine nitration
      decreased in response to IRL, and this reduction was mainly due to reduced
      tyrosine nitration of enolase and aldolase. We conclude that diaphragmatic NO
      derivatives levels decline in response to IRL and that the rise in diaphragmatic
      NOS protein expression may be a compensatory response designed to counterbalance
      the decline in NOS activity.

PMID- 17189324
TI  - Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody;
      SP-A1 content variation among individuals of varying age and pulmonary health.
AB  - The human surfactant protein A (SP-A) locus consists of two functional genes (SP
      A1, SP-A2) with gene-specific products exhibiting qualitative and quantitative
      differences. The aim here was twofold: 1) generate SP-A1 gene-specific antibody,
      and 2) use this to assess gene-specific SP-A content in the bronchoalveolar
      lavage fluid (BALF). An SP-A1-specific polyclonal antibody (hSP-A1_Ab(68-88)_Col)
      was raised in chicken, and its specificity was determined by immunoblot and ELISA
      using mammalian Chinese hamster ovary (CHO) cell-expressed SP-A1 and SP-A2
      variants and by immunofluorescence with stably transfected CHO cell lines
      expressing SP-A1 or SP-A2 variants. SP-A1 content was evaluated according to age
      and lung status. A gradual decrease (P < 0.05) in SP-A1/SP-A ratio was observed
      in healthy subjects (HS) with increased age, although no significant change was
      observed in total SP-A content among age groups. Total SP-A and SP-A1 content
      differed significantly between alveolar proteinosis (AP) patients and HS, with no
      significant difference observed in SP-A1/SP-A ratio between AP and HS. The cystic
      fibrosis (CF) ratio was significantly higher compared with AP, HS, and noncystic
      fibrosis (NCF), even though SP-A1 and total SP-A were decreased in CF compared
      with most of the other groups. The ratio was higher in culture-positive vs.
      culture-negative samples from CF and NCF (P = 0.031). A trend of an increased
      ratio was observed in culture-positive CF (0.590 +/- 0.10) compared with culture
      positive NCF (0.368 +/- 0.085). In summary, we developed and characterized an SP
      A1 gene-specific antibody and used it to identify gene-specific SP-A content in
      BALFs as a function of age and lung health.

PMID- 17189325
TI  - Arabidopsis transcriptome changes in response to phloem-feeding silverleaf
      whitefly nymphs. Similarities and distinctions in responses to aphids.
AB  - Phloem-feeding pests cause extensive crop damage throughout the world, yet little
      is understood about how plants perceive and defend themselves from these threats.
      The silverleaf whitefly (SLWF; Bemisia tabaci type B) is a good model for
      studying phloem-feeding insect-plant interactions, as SLWF nymphs cause little
      wounding and have a long, continuous interaction with the plant. Using the
      Affymetrix ATH1 GeneChip to monitor the Arabidopsis (Arabidopsis thaliana)
      transcriptome, 700 transcripts were found to be up-regulated and 556 down
      regulated by SLWF nymphs. Closer examination of the regulation of secondary
      metabolite (glucosinolate) and defense pathway genes after SLWF-instar feeding
      shows that responses were qualitatively and quantitatively different from chewing
      insects and aphids. In addition to the RNA profile distinctions, analysis of SLWF
      performance on wild-type and phytoalexin-deficient4 (pad4) mutants suggests aphid
      and SLWF interactions with Arabidopsis were distinct. While pad4-1 mutants were
      more susceptible to aphids, SLWF development on pad4-1 and wild-type plants was
      similar. Furthermore, although jasmonic acid genes were repressed and salicylic
      acid-regulated genes were induced after SLWF feeding, cytological staining of
      SLWF-infested tissue showed that pathogen defenses, such as localized cell death
      and hydrogen peroxide accumulation, were not observed. Like aphid and fungal
      pathogens, callose synthase gene RNAs accumulated and callose deposition was
      observed in SLWF-infested tissue. These results provide a more comprehensive
      understanding of phloem-feeding insect-plant interactions and distinguish SLWF
      global responses.

PMID- 17189326
TI  - Transgenic tobacco plants overexpressing chloroplastic ferredoxin-NADP(H)
      reductase display normal rates of photosynthesis and increased tolerance to
      oxidative stress.
AB  - Ferredoxin-NADP(H) reductase (FNR) catalyzes the last step of photosynthetic
      electron transport in chloroplasts, driving electrons from reduced ferredoxin to
      NADP+. This reaction is rate limiting for photosynthesis under a wide range of
      illumination conditions, as revealed by analysis of plants transformed with an
      antisense version of the FNR gene. To investigate whether accumulation of this
      flavoprotein over wild-type levels could improve photosynthetic efficiency and
      growth, we generated transgenic tobacco (Nicotiana tabacum) plants expressing a
      pea (Pisum sativum) FNR targeted to chloroplasts. The alien product distributed
      between the thylakoid membranes and the chloroplast stroma. Transformants grown
      at 150 or 700 micromol quanta m(-2) s(-1) displayed wild-type phenotypes
      regardless of FNR content. Thylakoids isolated from plants with a 5-fold FNR
      increase over the wild type displayed only moderate stimulation (approximately
      20%) in the rates of electron transport from water to NADP+. In contrast, when
      donors of photosystem I were used to drive NADP+ photoreduction, the activity was
      3- to 4-fold higher than the wild-type controls. Plants expressing various levels
      of FNR (from 1- to 3.6-fold over the wild type) failed to show significant
      differences in CO2 assimilation rates when assayed over a range of light
      intensities and CO2 concentrations. Transgenic lines exhibited enhanced tolerance
      to photooxidative damage and redox-cycling herbicides that propagate reactive
      oxygen species. The results suggest that photosynthetic electron transport has
      several rate-limiting steps, with FNR catalyzing just one of them.

PMID- 17189327
TI  - Diversity and evolution of CYCLOIDEA-like TCP genes in relation to flower
      development in Papaveraceae.
AB  - Monosymmetry evolved several times independently during flower evolution. In
      snapdragon (Antirrhinum majus), a key gene for monosymmetry is CYCLOIDEA (CYC),
      which belongs to the class II TCP gene family encoding transcriptional
      activators. We address the questions of the evolutionary history of this gene
      family and of possible recruitment of genes homologous to CYC in floral
      development and symmetry in the Papaveraceae. Two to three members of the class
      II TCP family were found in each species analyzed, two of which were CYC-like
      genes, on the basis of the presence of both the TCP and R conserved domains. The
      duplication that gave rise to these two paralogous lineages (named PAPACYL1 and
      PAPACYL2) probably predates the divergence of the two main clades within the
      Papaveraceae. Phylogenetic relationships among angiosperm class II TCP genes
      indicated that (1) PAPACYL genes were closest to Arabidopsis (Arabidopsis
      thaliana) AtTCP18, and a duplication at the base of the core eudicot would have
      given rise to two supplementary CYC-like lineages; and (2) at least three class
      II TCP genes were present in the ancestor of monocots and eudicots.
      Semiquantitative reverse transcription-polymerase chain reaction and in situ
      hybridization approaches in three species with different floral symmetry
      indicated that both PAPACYL paralogs were expressed during floral development. A
      pattern common to all three species was observed at organ junctions in
      inflorescences and flowers. Expression in the outer petals was specifically
      observed in the two species with nonactinomorphic flowers. Hypotheses concerning
      the ancestral pattern of expression and function of CYC-like genes and their
      possible role in floral development of Papaveraceae species leading to
      bisymmetric buds are discussed.

PMID- 17189328
TI  - Silverleaf whitefly induces salicylic acid defenses and suppresses effectual
      jasmonic acid defenses.
AB  - The basal defenses important in curtailing the development of the phloem-feeding
      silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis
      thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF
      infested and control plants. Salicylic acid (SA)-responsive gene transcripts
      accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1,
      BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and
      ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were
      repressed or not modulated in SLWF-infested leaves. To test for a role of SA and
      JA pathways in basal defense, SLWF development on mutant and transgenic lines
      that constitutively activate or impair defense pathways was determined. By
      monitoring the percentage of SLWF nymphs in each instar, we show that mutants
      that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF
      nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or
      impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore,
      when npr1 plants, which do not activate downstream SA defenses, were treated with
      methyl jasmonate, a dramatic delay in nymph development was observed.
      Collectively, these results showed that SLWF-repressed, JA-regulated defenses
      were associated with basal defense to the SLWF.

PMID- 17189329
TI  - Cross-species translocation of mRNA from host plants into the parasitic plant
      dodder.
AB  - An intriguing new paradigm in plant biology is that systemically mobile mRNAs
      play a role in coordinating development. In this process, specific mRNAs are
      loaded into the phloem transport stream for translocation to distant tissues,
      where they may impact on developmental processes. However, despite its potential
      significance for plant growth regulation, mRNA trafficking remains poorly
      understood and challenging to study. Here, we show that phloem-mobile mRNAs can
      also traffic between widely divergent species from a host to the plant parasite
      lespedeza dodder (Cuscuta pentagona Engelm.). Reverse transcription-polymerase
      chain reaction and microarray analysis were used to detect specific tomato
      (Lycopersicon esculentum Mill.) transcripts in dodder grown on tomato that were
      not present in control dodder grown on other host species. Foreign transcripts
      included LeGAI, which has previously been shown to be translocated in the phloem,
      as well as nine other transcripts not reported to be mobile. Dodders are
      parasitic plants that obtain resources by drawing from the phloem of a host plant
      and have joint plasmodesmata with host cortical cells. Although viruses are known
      to move between dodder and its hosts, translocation of endogenous plant mRNA has
      not been reported. These results point to a potentially new level of interspecies
      communication, and raise questions about the ability of parasites to recognize,
      use, and respond to transcripts acquired from their hosts.

PMID- 17189330
TI  - Transcriptional profiling of the Arabidopsis embryo.
AB  - We have used laser-capture microdissection to isolate RNA from discrete tissues
      of globular, heart, and torpedo stage embryos of Arabidopsis (Arabidopsis
      thaliana). This was amplified and analyzed by DNA microarray using the Affymetrix
      ATH1 GeneChip, representing approximately 22,800 Arabidopsis genes. Cluster
      analysis showed that spatial differences in gene expression were less significant
      than temporal differences. Time course analysis reveals the dynamics and
      complexity of gene expression in both apical and basal domains of the developing
      embryo, with several classes of synexpressed genes identifiable. The transition
      from globular to heart stage is associated in particular with an up-regulation of
      genes involved in cell cycle control, transcriptional regulation, and energetics
      and metabolism. The transition from heart to torpedo stage is associated with a
      repression of cell cycle genes and an up-regulation of genes encoding storage
      proteins, and pathways of cell growth, energy, and metabolism. The torpedo stage
      embryo shows strong functional differentiation in the root and cotyledon, as
      inferred from the classes of genes expressed in these tissues. The time course of
      expression of the essential EMBRYO-DEFECTIVE genes shows that most are expressed
      at unchanging levels across all stages of embryogenesis. We show how identified
      genes can be used to generate cell type-specific markers and promoter activities
      for future application in cell biology.

PMID- 17189331
TI  - Xylella fastidiosa infection and ethylene exposure result in xylem and water
      movement disruption in grapevine shoots.
AB  - It is conventionally thought that multiplication of the xylem-limited bacterium
      Xylella fastidiosa (Xf) within xylem vessels is the sole factor responsible for
      the blockage of water movement in grapevines (Vitis vinifera) affected by
      Pierce's disease. However, results from our studies have provided substantial
      support for the idea that vessel obstructions, and likely other aspects of the
      Pierce's disease syndrome, result from the grapevine's active responses to the
      presence of Xf, rather than to the direct action of the bacterium. The use of
      magnetic resonance imaging (MRI) to observe the distribution of water within the
      xylem has allowed us to follow nondestructively the development of vascular
      system obstructions subsequent to inoculation of grapevines with Xf. Because we
      have hypothesized a role for ethylene produced in vines following infection, the
      impact of vine ethylene exposure on obstruction development was also followed
      using MRI. In both infected and ethylene-exposed plants, MRI shows that an
      important proportion of the xylem vessels become progressively air embolized
      after the treatments. The loss of xylem water-transporting function, assessed by
      MRI, has been also correlated with a decrease in stem-specific hydraulic
      conductivity (K(S)) and the presence of tyloses in the lumens of obstructed water
      conduits. We have observed that the ethylene production of leaves from infected
      grapevines is greater than that from healthy vines and, therefore, propose that
      ethylene may be involved in a series of cellular events that coordinates the
      vine's response to the pathogen.

PMID- 17189332
TI  - Two Arabidopsis genes (IPMS1 and IPMS2) encode isopropylmalate synthase, the
      branchpoint step in the biosynthesis of leucine.
AB  - Heterologous expression of the Arabidopsis (Arabidopsis thaliana) IPMS1
      (At1g18500) and IPMS2 (At1g74040) cDNAs in Escherichia coli yields
      isopropylmalate synthases (IPMSs; EC 2.3.3.13). These enzymes catalyze the first
      dedicated step in leucine (Leu) biosynthesis, an aldol-type condensation of
      acetyl-coenzyme A (CoA) and 2-oxoisovalerate yielding isopropylmalate. Most
      biochemical properties of IPMS1 and IPMS2 are similar: broad pH optimum around pH
      8.5, Mg2+ as cofactor, feedback inhibition by Leu, Km for 2-oxoisovalerate of
      approximately 300 microM, and a Vmax of approximately 2 x 10(3) micromol min(-1)
      g(-1). However, IPMS1 and IPMS2 differ in their Km for acetyl-CoA (45 microM and
      16 microM, respectively) and apparent quaternary structure (dimer and tetramer,
      respectively). A knockout insertion mutant for IPMS1 showed an increase in valine
      content but no changes in Leu content; two insertion mutants for IPMS2 did not
      show any changes in soluble amino acid content. Apparently, in planta each gene
      can adequately compensate for the absence of the other, consistent with available
      microarray and reverse transcription-polymerase chain reaction data that show
      that both genes are expressed in all organs at all developmental stages. Both
      encoded proteins accept 2-oxo acid substrates in vitro ranging in length from
      glyoxylate to 2-oxohexanoate, and catalyze at a low rate the condensation of
      acetyl-CoA and 4-methylthio-2-oxobutyrate, i.e. a reaction involved in
      glucosinolate chain elongation normally catalyzed by methylthioalkylmalate
      synthases. The evolutionary relationship between IPMS and methylthioalkylmalate
      synthase enzymes is discussed in view of their amino acid sequence identity (60%)
      and overlap in substrate specificity.

PMID- 17189333
TI  - Ectopic expression of ABSCISIC ACID 2/GLUCOSE INSENSITIVE 1 in Arabidopsis
      promotes seed dormancy and stress tolerance.
AB  - Abscisic acid (ABA) is an important phytohormone that plays a critical role in
      seed development, dormancy, and stress tolerance. 9-cis-Epoxycarotenoid
      dioxygenase is the key enzyme controlling ABA biosynthesis and stress tolerance.
      In this study, we investigated the effect of ectopic expression of another ABA
      biosynthesis gene, ABA2 (or GLUCOSE INSENSITIVE 1 [GIN1]) encoding a short-chain
      dehydrogenase/reductase in Arabidopsis (Arabidopsis thaliana). We show that ABA2
      overexpressing transgenic plants with elevated ABA levels exhibited seed
      germination delay and more tolerance to salinity than wild type when grown on
      agar plates and/or in soil. However, the germination delay was abolished in
      transgenic plants showing ABA levels over 2-fold higher than that of wild type
      grown on 250 mm NaCl. The data suggest that there are distinct mechanisms
      underlying ABA-mediated inhibition of seed germination under diverse stress. The
      ABA-deficient mutant aba2, with a shorter primary root, can be restored to normal
      root growth by exogenous application of ABA, whereas transgenic plants
      overexpressing ABA2 showed normal root growth. The data reflect that the basal
      levels of ABA are essential for maintaining normal primary root elongation.
      Furthermore, analysis of ABA2 promoter activity with ABA2::beta-glucuronidase
      transgenic plants revealed that the promoter activity was enhanced by multiple
      prolonged stresses, such as drought, salinity, cold, and flooding, but not by
      short-term stress treatments. Coincidently, prolonged drought stress treatment
      led to the up-regulation of ABA biosynthetic and sugar-related genes. Thus, the
      data support ABA2 as a late expression gene that might have a fine-tuning
      function in mediating ABA biosynthesis through primary metabolic changes in
      response to stress.

PMID- 17189334
TI  - Modulation of ethylene responses affects plant salt-stress responses.
AB  - Ethylene signaling plays important roles in multiple aspects of plant growth and
      development. Its functions in abiotic stress responses remain largely unknown.
      Here, we report that alteration of ethylene signaling affected plant salt-stress
      responses. A type II ethylene receptor homolog gene NTHK1 (Nicotiana tabacum
      histidine kinase 1) from tobacco (N. tabacum) conferred salt sensitivity in NTHK1
      transgenic Arabidopsis (Arabidopsis thaliana) plants as judged from the
      phenotypic change, the relative electrolyte leakage, and the relative root growth
      under salt stress. Ethylene precursor 1-aminocyclopropane-1-carboxylic acid
      suppressed the salt-sensitive phenotype. Analysis of Arabidopsis ethylene
      receptor gain-of-function mutants further suggests that receptor function may
      lead to salt-sensitive responses. Mutation of EIN2, a central component in
      ethylene signaling, also results in salt sensitivity, suggesting that EIN2
      mediated signaling is beneficial for plant salt tolerance. Overexpression of the
      NTHK1 gene or the receptor gain-of-function activated expression of salt
      responsive genes AtERF4 and Cor6.6. In addition, the transgene NTHK1 mRNA was
      accumulated under salt stress, suggesting a posttranscriptional regulatory
      mechanism. These findings imply that ethylene signaling may be required for plant
      salt tolerance.

PMID- 17189335
TI  - Desiccation and zinc binding induce transition of tomato abscisic acid stress
      ripening 1, a water stress- and salt stress-regulated plant-specific protein,
      from unfolded to folded state.
AB  - Abscisic acid stress ripening 1 (ASR1) is a low molecular weight plant-specific
      protein encoded by an abiotic stress-regulated gene. Overexpression of ASR1 in
      transgenic plants increases their salt tolerance. The ASR1 protein possesses a
      zinc-dependent DNA-binding activity. The DNA-binding site was mapped to the
      central part of the polypeptide using truncated forms of the protein. Two
      additional zinc-binding sites were shown to be localized at the amino terminus of
      the polypeptide. ASR1 protein is presumed to be an intrinsically unstructured
      protein using a number of prediction algorithms. The degree of order of ASR1 was
      determined experimentally using nontagged recombinant protein expressed in
      Escherichia coli and purified to homogeneity. Purified ASR1 was shown to be
      unfolded using dynamic light scattering, gel filtration, microcalorimetry,
      circular dichroism, and Fourier transform infrared spectrometry. The protein was
      shown to be monomeric by analytical ultracentrifugation. Addition of zinc ions
      resulted in a global change in ASR1 structure from monomer to homodimer. Upon
      binding of zinc ions, the protein becomes ordered as shown by Fourier transform
      infrared spectrometry and microcalorimetry, concomitant with dimerization. Tomato
      (Solanum lycopersicum) leaf soluble ASR1 is unstructured in the absence of added
      zinc and gains structure upon binding of the metal ion. The effect of zinc
      binding on ASR1 folding and dimerization is discussed.

PMID- 17189336
TI  - Strategies for functional validation of genes involved in reproductive stages of
      orchids.
AB  - Plants in the largest family of angiosperms, Orchidaceae, are diverse in both
      specialized pollination and ecological strategies and provide a rich source for
      investigating evolutionary relationships and developmental biology. However,
      studies in orchids have been hindered by several challenges that include low
      transformation efficiency and long regeneration time. To overcome such obstacles,
      we selected a symptomless cymbidium mosaic virus (CymMV) isolate for constructing
      virus-induced gene-silencing vectors. The feasibility of the virus vectors was
      first assessed with use of an orchid phytoene desaturase gene. The vector was
      able to induce gene silencing in orchids; however, because of the slow growth of
      orchids, the commonly used phytoene desaturase gene was not a good visual marker
      in orchids. We inserted a 150-nucleotide unique region of a B-class MADS-box
      family gene, PeMADS6, into pCymMV-pro60. The transcription level of PeMADS6 in
      inoculated Phalaenopsis plants was reduced by up to 73%, but no effect was
      observed for other MADS-box family genes. In contrast, in Phalaenopsis plants
      inoculated with CymMV transcripts containing 500 nucleotides of PeMADS6, a
      conserved region among MADS-box genes, the transcription level of PeMADS6 and the
      B- and C-class MADS-box genes was reduced by up to 97.8% as compared with plants
      inoculated with the vector alone. Flower morphology was affected in the MADS-box
      family gene-silenced plants as well. This in vivo experiment demonstrates an
      efficient way to study genes involved in the reproductive stage of plants with a
      long life cycle.

PMID- 17189337
TI  - Purdue ionomics information management system. An integrated functional genomics
      platform.
AB  - The advent of high-throughput phenotyping technologies has created a deluge of
      information that is difficult to deal with without the appropriate data
      management tools. These data management tools should integrate defined workflow
      controls for genomic-scale data acquisition and validation, data storage and
      retrieval, and data analysis, indexed around the genomic information of the
      organism of interest. To maximize the impact of these large datasets, it is
      critical that they are rapidly disseminated to the broader research community,
      allowing open access for data mining and discovery. We describe here a system
      that incorporates such functionalities developed around the Purdue University
      high-throughput ionomics phenotyping platform. The Purdue Ionomics Information
      Management System (PiiMS) provides integrated workflow control, data storage, and
      analysis to facilitate high-throughput data acquisition, along with integrated
      tools for data search, retrieval, and visualization for hypothesis development.
      PiiMS is deployed as a World Wide Web-enabled system, allowing for integration of
      distributed workflow processes and open access to raw data for analysis by
      numerous laboratories. PiiMS currently contains data on shoot concentrations of
      P, Ca, K, Mg, Cu, Fe, Zn, Mn, Co, Ni, B, Se, Mo, Na, As, and Cd in over 60,000
      shoot tissue samples of Arabidopsis (Arabidopsis thaliana), including ethyl
      methanesulfonate, fast-neutron and defined T-DNA mutants, and natural accession
      and populations of recombinant inbred lines from over 800 separate experiments,
      representing over 1,000,000 fully quantitative elemental concentrations. PiiMS is
      accessible at www.purdue.edu/dp/ionomics.

PMID- 17189338
TI  - MPB2C, a microtubule-associated plant factor, is required for microtubular
      accumulation of tobacco mosaic virus movement protein in plants.
AB  - Movement protein binding 2C (MPB2C) is a plant endogenous microtubule-associated
      protein previously identified as an interaction partner of tobacco (Nicotiana
      tabacum) mosaic virus movement protein (TMV-MP). In this work, the role of MPB2C
      in cell-to-cell transport of TMV-MP, viral spread of TMV, and subcellular
      localization of TMV-MP was examined. To this end, plants with reduced MPB2C
      levels were generated by a gene-silencing strategy. Local and systemic spread of
      TMV and cell-to-cell movement of TMV-MP were unimpaired in MPB2C-silenced plants
      as compared to nonsilenced plants, indicating that MPB2C is not required for
      intercellular transport of TMV-MP itself or spread of TMV. However, a clear
      change in subcellular distribution of TMV-MP characterized by a nearly complete
      loss of microtubular localization was observed in MPB2C-silenced plants. This
      result shows that the MPB2C is a central player in determining the complex
      subcellular localization of TMV-MP, in particular its microtubular accumulation,
      a phenomenon that has been frequently observed and whose role is still under
      discussion. Clearly, MPB2C mediated accumulation of TMV-MP at microtubules is not
      required for intercellular spread but may be a means to withdraw the TMV-MP from
      the cell-to-cell transport pathway.

PMID- 17189339
TI  - Proteome dynamics during plastid differentiation in rice.
AB  - We have analyzed proteome dynamics during light-induced development of rice
      (Oryza sativa) chloroplasts from etioplasts using quantitative two-dimensional
      gel electrophoresis and tandem mass spectrometry protein identification. In the
      dark, the etioplast allocates the main proportion of total protein mass to
      carbohydrate and amino acid metabolism and a surprisingly high number of proteins
      to the regulation and expression of plastid genes. Chaperones, proteins for
      photosynthetic energy metabolism, and enzymes of the tetrapyrrole pathway were
      identified among the most abundant etioplast proteins. The detection of 13 N
      terminal acetylated peptides allowed us to map the exact localization of the
      transit peptide cleavage site, demonstrating good agreement with the prediction
      for most proteins. Based on the quantitative etioplast proteome map, we examined
      early light-induced changes during chloroplast development. The transition from
      heterotrophic metabolism to photosynthesis-supported autotrophic metabolism was
      already detectable 2 h after illumination and affected most essential metabolic
      modules. Enzymes in carbohydrate metabolism, photosynthesis, and gene expression
      were up-regulated, whereas enzymes in amino acid and fatty acid metabolism were
      significantly decreased in relative abundance. Enzymes involved in nucleotide
      metabolism, tetrapyrrole biosynthesis, and redox regulation remained unchanged.
      Phosphoprotein-specific staining at different time points during chloroplast
      development revealed light-induced phosphorylation of a nuclear-encoded plastid
      RNA-binding protein, consistent with changes in plastid RNA metabolism.
      Quantitative information about all identified proteins and their regulation by
      light is available in plprot, the plastid proteome database
      (http://www.plprot.ethz.ch).

PMID- 17189340
TI  - Dynamics of a mobile RNA of potato involved in a long-distance signaling pathway.
AB  - BEL1-like transcription factors interact with Knotted1 types to regulate numerous
      developmental processes. In potato (Solanum tuberosum), the BEL1 transcription
      factor St BEL5 and its protein partner POTH1 regulate tuber formation by
      mediating hormone levels in the stolon tip. The accumulation of St BEL5 RNA
      increases in response to short-day photoperiods, inductive for tuber formation.
      RNA detection methods and heterografting experiments demonstrate that BEL5
      transcripts are present in phloem cells and move across a graft union to localize
      in stolon tips, the site of tuber induction. This movement of RNA to stolon tips
      is correlated with enhanced tuber production. Overexpression of BEL5 transcripts
      that include the untranslated sequences of the BEL5 transcript endows transgenic
      lines with the capacity to overcome the inhibitory effects of long days on tuber
      formation. Addition of the untranslated regions leads to preferential
      accumulation of the BEL5 RNA in stolon tips under short-day conditions. Using a
      leaf-specific promoter, the movement of BEL5 RNA to stolon tips was facilitated
      by a short-day photoperiod, and this movement was correlated with enhanced tuber
      production. These results implicate the transcripts of St BEL5 in a long-distance
      signaling pathway that are delivered to the target organ via the phloem stream.

PMID- 17189341
TI  - The plant-specific ssDNA binding protein OSB1 is involved in the stoichiometric
      transmission of mitochondrial DNA in Arabidopsis.
AB  - Plant mitochondrial genomes exist in a natural state of heteroplasmy, in which
      substoichiometric levels of alternative mitochondrial DNA (mtDNA) molecules
      coexist with the main genome. These subgenomes either replicate autonomously or
      are created by infrequent recombination events. We found that Arabidopsis
      thaliana OSB1 (for Organellar Single-stranded DNA Binding protein1) is required
      for correct stoichiometric mtDNA transmission. OSB1 is part of a family of plant
      specific DNA binding proteins that are characterized by a novel motif that is
      required for single-stranded DNA binding. The OSB1 protein is targeted to
      mitochondria, and promoter-beta-glucuronidase fusion showed that the gene is
      expressed in budding lateral roots, mature pollen, and the embryo sac of
      unfertilized ovules. OSB1 T-DNA insertion mutants accumulate mtDNA homologous
      recombination products and develop phenotypes of leaf variegation and distortion.
      The mtDNA rearrangements occur in two steps: first, homozygous mutants accumulate
      subgenomic levels of homologous recombination products; second, in subsequent
      generations, one of the recombination products becomes predominant. After the
      second step, the process is no longer reversible by backcrossing. Thus, OSB1
      participates in controlling the stoichiometry of alternative mtDNA forms
      generated by recombination. This regulation could take place in gametophytic
      tissues to ensure the transmission of a functional mitochondrial genome.

PMID- 17189342
TI  - Somatic cytokinesis and pollen maturation in Arabidopsis depend on TPLATE, which
      has domains similar to coat proteins.
AB  - TPLATE was previously identified as a potential cytokinesis protein targeted to
      the cell plate. Disruption of TPLATE in Arabidopsis thaliana leads to the
      production of shriveled pollen unable to germinate. Vesicular
      compartmentalization of the mature pollen is dramatically altered, and large
      callose deposits accumulate near the intine cell wall layer. Green fluorescent
      protein (GFP)-tagged TPLATE expression under the control of the pollen promoter
      Lat52 complements the phenotype. Downregulation of TPLATE in Arabidopsis
      seedlings and tobacco (Nicotiana tabacum) BY-2 suspension cells results in
      crooked cell walls and cell plates that fail to insert into the mother wall.
      Besides accumulating at the cell plate, GFP-fused TPLATE is temporally targeted
      to a narrow zone at the cell cortex where the cell plate connects to the mother
      wall. TPLATE-GFP also localizes to subcellular structures that accumulate at the
      pollen tube exit site in germinating pollen. Ectopic callose depositions observed
      in mutant pollen also occur in RNA interference plants, suggesting that TPLATE is
      implicated in cell wall modification. TPLATE contains domains similar to adaptin
      and beta-COP coat proteins. These data suggest that TPLATE functions in vesicle
      trafficking events required for site-specific cell wall modifications during
      pollen germination and for anchoring of the cell plate to the mother wall at the
      correct cortical position.

PMID- 17189343
TI  - Defects in CTP:PHOSPHORYLETHANOLAMINE CYTIDYLYLTRANSFERASE affect embryonic and
      postembryonic development in Arabidopsis.
AB  - A TILLING strategy (for targeting-induced local-scale lesions in genomes) was
      used in Arabidopsis thaliana to isolate mutants of a gene encoding
      CTP:PHOSPHORYLETHANOLAMINE CYTIDYLYLTRANSFERASE (PECT; EC 2.7.7.14), a rate
      limiting enzyme in phosphatidylethanolamine biosynthesis. A null mutation, pect1
      6, caused embryo abortion before the octant stage. However, reciprocal crosses
      revealed that pect1-6 caused no significant gametophytic defect. In pect1-4, PECT
      activity was decreased by 74%. Growth was generally normal in these mutants,
      despite delays in embryo maturation and reduced fertility. At low temperatures,
      however, homozygotic pect1-4 plants displayed dwarfism. PECT activity was
      decreased by 47% in heterozygotic pect1-6 plants and by 80% in pect1-4/pect1-6 F1
      plants, which also displayed a small but significant decrease of
      phosphatidylethanolamine and a reciprocal increase in phosphatidylcholine. These
      lipid changes were fully reversed by wild-type PECT1 expression. pect1-4/pect1-6
      F1 plants displayed severe dwarfism, tissue abnormalities, and low fertility,
      which was attributable in part to inhibition of anther, embryo, and ovule
      development, as was the reduced fertility of pect1-4 seedlings. PECT1 cDNA
      expression under the control of an inducible promoter partially rectified the
      mutant phenotypes observed in pect1-4/pect1-6 F1 seedlings, indicating that
      malfunctions in different tissues have a synergistic effect on the mutant
      phenotypes.

PMID- 17189344
TI  - A multidrug resistance transporter in Magnaporthe is required for host
      penetration and for survival during oxidative stress.
AB  - In prokaryotes and eukaryotes, multidrug resistance (MDR) transporters use energy
      dependent efflux action to regulate the intracellular levels of antibiotic or
      xenobiotic compounds. Using mutational analysis of ABC3, we define an important
      role for such MDR-based efflux during the host penetration step of Magnaporthe
      grisea pathogenesis. Mutants lacking ABC3 were completely nonpathogenic but were
      surprisingly capable of penetrating thin cellophane membranes to some extent. The
      inability of abc3Delta to penetrate the host surface was most likely a
      consequence of excessive buildup of peroxide and accumulation of an inhibitory
      metabolite(s) within the mutant appressoria. Treatment with antioxidants
      partially suppressed the host penetration defects in the abc3Delta mutant.
      abc3Delta was highly sensitive to oxidative stress and was unable to survive the
      host environment and invasive growth conditions. ABC3 transcript levels were
      redox-regulated, and on host surfaces, the activation of ABC3 occurred during
      initial stages of blast disease establishment. An Abc3-green fluorescent protein
      fusion localized to the plasma membrane in early appressoria (and in penetration
      hyphae) but became predominantly vacuolar during appressorial maturity. We
      propose that ABC3 function helps Magnaporthe to cope with cytotoxicity and
      oxidative stress within the appressoria during early stages of infection-related
      morphogenesis and likely imparts defense against certain antagonistic and
      xenobiotic conditions encountered during pathogenic development.

PMID- 17189345
TI  - Identification of important regions for ethylene binding and signaling in the
      transmembrane domain of the ETR1 ethylene receptor of Arabidopsis.
AB  - The ethylene binding domain (EBD) of the Arabidopsis thaliana ETR1 receptor is
      modeled as three membrane-spanning helices. We surveyed ethylene binding activity
      in different kingdoms and performed a bioinformatic analysis of the EBD. Ethylene
      binding is confined to land plants, Chara, and a group of cyanobacteria but is
      largely absent in other organisms, consistent with our finding that EBD-like
      sequences are overrepresented among plant and cyanobacterial species. We made
      amino acid substitutions in 37 partially or completely conserved residues of the
      EBD and assayed their effects on ethylene binding and signaling. Mutations
      primarily in residues in Helices I and II midregions eliminated ethylene binding
      and conferred constitutive signaling, consistent with the inverse-agonist model
      of ethylene receptor signaling and indicating that these residues define the
      ethylene binding pocket. The largest class of mutations, clustered near the
      cytoplasmic ends of Helices I and III, gave normal ethylene binding activity yet
      still conferred constitutive signaling. Therefore, these residues may play a role
      in turning off the signal transmitter domain of the receptor. By contrast, only
      two mutations were loss of function with respect to signaling. These findings
      yield insight into the structure and function of the EBD and suggest a conserved
      role of the EBD as a negative regulator of the signal transmitter domain.

PMID- 17189347
TI  - Heart failure attenuates muscle metaboreflex control of ventricular contractility
      during dynamic exercise.
AB  - Underperfusion of active skeletal muscle elicits a reflex pressor response termed
      the muscle metaboreflex (MMR). In normal dogs during mild exercise, MMR
      activation causes large increases in cardiac output (CO) and mean arterial
      pressure (MAP); however, in heart failure (HF) although MAP increases, the rise
      in CO is virtually abolished, which may be due to an impaired ability to increase
      left ventricular contractility (LVC). The objective of the present study was to
      determine whether the increases in LVC seen with MMR activation during dynamic
      exercise in normal animals are abolished in HF. Conscious dogs were chronically
      instrumented to measure CO, MAP, and left ventricular (LV) pressure and volume.
      LVC was calculated from pressure-volume loop analysis [LV maximal elastance
      (E(max)) and preload-recruitable stroke work (PRSW)] at rest and during mild and
      moderate exercise under free-flow conditions and with MMR activation (via partial
      occlusion of hindlimb blood flow) before and after rapid ventricular pacing
      induced HF. In control experiments, MMR activation at both workloads [mild
      exercise (3.2 km/h) and moderate exercise (6.4 km/h at 10% grade)] significantly
      increased CO, E(max), and PRSW. In contrast, after HF was induced, CO, E(max),
      and PRSW were significantly lower at rest. Although CO increased significantly
      from rest to exercise, E(max) and PRSW did not change. In addition, MMR
      activation caused no significant change in CO, E(max), or PRSW at either
      workload. We conclude that MMR causes large increases in LVC in normal animals
      but that this ability is abolished in HF.

PMID- 17189348
TI  - Regulation of lymphatic capillary regeneration by interstitial flow in skin.
AB  - Decreased interstitial flow (IF) in secondary lymphedema is coincident with poor
      physiological lymphatic regeneration. However, both the existence and direction
      of causality between IF and lymphangiogenesis remain unclear. This is primarily
      because the role of IF and its importance relative to the action of the
      prolymphangiogenic growth factor vascular endothelial growth factor (VEGF)-C
      (which signals primarily through its receptor VEGFR-3) are poorly understood. To
      clarify this, we explored the cooperative roles of VEGFR-3 and IF in a mouse
      model of lymphangiogenesis in regenerating skin. Specifically, a region of
      lymphangiogenesis was created by substituting a portion of mouse tail skin with a
      collagen gel within which lymphatic capillaries completely regenerate over a
      period of 60 days. The relative importance of IF and VEGF-C signaling were
      evaluated by either inhibiting VEGFR-3 signaling with antagonistic antibodies or
      by reducing IF. In some cases, VEGF-C signaling was then increased with exogenous
      protein. To clarify the role of IF, the distribution of endogenous matrix
      metalloproteinases (MMPs) and VEGF-C within the regenerating region was
      determined. It was found that inhibition of either VEGFR-3 or IF suppressed
      endogenous lymphangiogenesis. Reduction of IF was found to decrease lymphatic
      migration and transport of endogenous MMP and VEGF-C through the regenerating
      region. Therapeutic VEGF-C administration restored lymphangiogenesis following
      inhibition of VEGFR-3 but did not increase lymphangiogenesis following inhibition
      of IF. These results identify IF as an important regulator of the pro
      lymphangiogenic action of VEGF-C.

PMID- 17189349
TI  - Ryanodine receptor dysfunction and triggered activity in the heart.
AB  - Arrhythmogenesis has been increasingly linked to cardiac ryanodine receptor (RyR)
      dysfunction. However, the mechanistic relationship between abnormal RyR function
      and arrhythmogenesis in the heart is not clear. We hypothesize that, under
      abnormal RyR conditions, triggered activity will be caused by spontaneous calcium
      release (SCR) events that depend on transmural heterogeneities of calcium
      handling. We performed high-resolution optical mapping of intracellular calcium
      and transmembrane potential in the canine left ventricular wedge preparation (n =
      28). Rapid pacing was used to initiate triggered activity under normal and
      abnormal RyR conditions induced by FKBP12.6 dissociation and beta-adrenergic
      stimulation (20-150 microM rapamycin, 0.2 microM isoproterenol). Under abnormal
      RyR conditions, almost all preparations experienced SCRs and triggered activity,
      in contrast to control, rapamycin, or isoproterenol conditions alone.
      Furthermore, under abnormal RyR conditions, complex arrhythmias (monomorphic and
      polymorphic tachycardia) were commonly observed. After washout of rapamycin and
      isoproterenol, no triggered activity was observed. Surprisingly, triggered
      activity and SCRs occurred preferentially near the epicardium but not the
      endocardium (P < 0.01). Interestingly, the occurrence of triggered activity and
      SCR events could not be explained by cytoplasmic calcium levels, but rather by
      fast calcium reuptake kinetics. These data suggest that, under abnormal RyR
      conditions, triggered activity is caused by multiple SCR events that depend on
      the faster calcium reuptake kinetics near the epicardium. Furthermore, multiple
      regions of SCR may be a mechanism for multifocal arrhythmias associated with RyR
      dysfunction.

PMID- 17189346
TI  - A family of microRNAs present in plants and animals.
AB  - Although many miRNAs are deeply conserved within each kingdom, none are known to
      be conserved between plants and animals. We identified Arabidopsis thaliana
      miR854 and miR855, two microRNAs (miRNAs) with multiple binding sites in the 3'
      untranslated region (3'UTR) of OLIGOURIDYLATE binding PROTEIN1b (At UBP1b),
      forming miRNA:mRNA interactions similar to those that cause translational
      repression/mRNA cleavage in animals. At UBP1b encodes a member of a heterogeneous
      nuclear RNA binding protein (hnRNP) family. The 3'UTR of At UBP1b is sufficient
      to repress reporter protein expression in tissues expressing miR854 or miR855
      (rosette leaves and flowers, respectively) but not where both miRNAs are absent
      (cauline leaves). Intergenic regions containing sequences closely resembling
      miR854 are predicted to fold into stable miRNA precursors in animals, and members
      of the miR854 family are expressed in Caenorhabditis elegans, Mus musculus, and
      Homo sapiens, all with imperfect binding sites in the 3'UTR of genes encoding the
      T cell Intracellular Antigen-Related protein, an hnRNP of the UBP1 family.
      Potential binding sites for miR854 are absent from UBP1-like genes in fungi
      lacking the miRNA biogenetic machinery. Our results indicate that plants and
      animals share miRNAs of the miR854 family, suggesting a common origin of these
      miRNAs as regulators of basal transcriptional mechanisms.

PMID- 17189350
TI  - KATP channel knockout worsens myocardial calcium stress load in vivo and impairs
      recovery in stunned heart.
AB  - Gene knockout of the KCNJ11-encoded Kir6.2 ATP-sensitive K(+) (K(ATP)) channel
      implicates this stress-response element in the safeguard of cardiac homeostasis
      under imposed demand. K(ATP) channels are abundant in ventricular sarcolemma,
      where subunit expression appears to vary between the sexes. A limitation,
      however, in establishing the full significance of K(ATP) channels in the intact
      organism has been the inability to monitor in vivo the contribution of the
      channel to intracellular calcium handling and the superimposed effect of sex that
      ultimately defines heart function. Here, in vivo manganese-enhanced cardiac
      magnetic resonance imaging revealed, under dobutamine stress, a significantly
      greater accumulation of calcium in both male and female K(ATP) channel knockout
      (Kir6.2-KO) mice compared with sex- and age-matched wild-type (WT) counterparts,
      with greatest calcium load in Kir6.2-KO females. This translated, poststress,
      into a sustained contracture manifested by reduced end-diastolic volumes in
      K(ATP) channel-deficient mice. In response to ischemia-induced stunning, male and
      female Kir6.2-KO hearts demonstrated accelerated time to contracture and
      increased peak contracture compared with WT. The outcome on reperfusion, in both
      male and female Kir6.2-KO hearts, was a transient reduction in systolic
      performance, measured as rate-pressure product compared with WT, with protracted
      increase in left ventricular end-diastolic pressure, exaggerated in female
      knockout hearts, despite comparable leakage of creatine kinase across groups.
      Kir6.2-KO hearts were rescued from diastolic dysfunction by agents that target
      alternative pathways of calcium handling. Thus K(ATP) channel deficit confers a
      greater susceptibility to calcium overload in vivo, accentuated in female hearts,
      impairing contractile recovery under various conditions of high metabolic demand.

PMID- 17189352
TI  - Immunogold labeling study of the distribution of GLUT-1 and GLUT-4 in cardiac
      tissue following stimulation by insulin or ischemia.
AB  - Whereas glucose transporter 1 (GLUT-1) is thought to be responsible for basal
      glucose uptake in cardiac myocytes, little is known about its relative
      distribution between the different plasma membranes and cell types in the heart.
      GLUT-4 translocates to the myocyte surface to increase glucose uptake in response
      to a number of stimuli. The mechanisms underlying ischemia- and insulin-mediated
      GLUT-4 translocation are known to be different, raising the possibility that the
      intracellular destinations of GLUT-4 following these stimuli also differ. Using
      immunogold labeling, we describe the cellular localization of these two
      transporters and investigate whether insulin and ischemia induce differential
      translocation of GLUT-4 to different cardiac membranes. Immunogold labeling of
      GLUT-1 and GLUT-4 was performed on left ventricular sections from isolated hearts
      following 30 min of either insulin, ischemia, or control perfusion. In control
      tissue, GLUT-1 was predominantly (76%) localized in the capillary endothelial
      cells, with only 24% of total cardiac GLUT-1 present in myocytes. GLUT-4 was
      found predominantly in myocytes, distributed between sarcolemmal and T tubule
      membranes (1.84 +/- 0.49 and 1.54 +/- 0.33 golds/microm, respectively) and
      intracellular vesicles (127 +/- 18 golds/microm(2)). Insulin increased T tubule
      membrane GLUT-4 content (2.8 +/- 0.4 golds/microm, P < 0.05) but had less effect
      on sarcolemmal GLUT-4 (1.72 +/- 0.53 golds/microm). Ischemia induced greater GLUT
      4 translocation to both membrane types (4.25 +/- 0.84 and 4.01 +/- 0.27
      golds/microm, respectively P < 0.05). The localization of GLUT-1 suggests a
      significant role in transporting glucose across the capillary wall before myocyte
      uptake via GLUT-1 and GLUT-4. We demonstrate independent spatial translocation of
      GLUT-4 under insulin or ischemic stimulation and propose independent roles for T
      tubular and sarcolemmal GLUT-4.

PMID- 17189351
TI  - The rate of tension recovery in cardiac muscle correlates with the relative
      residual tension prevailing after restretch.
AB  - Isolated cardiac muscles generate tension more quickly at higher levels of Ca(2+)
      activation. We investigated the molecular mechanisms underlying this effect in
      permeabilized rat myocardial preparations by measuring the rate of tension
      recovery following brief shortening/restretch perturbations. Separate series of
      experiments used Ca(2+)-activating solutions with different pH values (pH 6.75,
      7.00, and 7.25) and different phosphate (P(i)) concentrations (0, 2.5, and 5.0 mM
      added P(i)) to modulate the recovery kinetics. Subsequent analysis showed that
      the rate of tension recovery correlated (P < 0.001) with the relative residual
      tension, that is, the minimum tension measured immediately after restretch
      normalized to the steady-state isometric tension for the experimental condition.
      This new finding suggests that the rate at which cardiac muscles develop force
      increases with the proportion of cross bridges bound to the thin filament and is
      strong evidence of cooperative contractile activation.

PMID- 17189353
TI  - Interanimal variability in preexisting collaterals is a major factor determining
      outcome in experimental angiogenesis trials.
AB  - Despite numerous animal trials reporting that cell therapy promotes collateral
      flow, clinical trials have not convincingly shown benefit. Patient-related risk
      factors are often used to explain these discrepancies. However, during the course
      of our own angiogenesis studies using mice, we noted large anatomical variability
      in collateral vessels. The purpose of the present investigation was to define how
      important this factor might be in determining intervention outcomes. Hindlimb
      ischemia was induced in BALB/c mice by ligating the superficial femoral artery.
      After 24 h, animals were treated by injecting the adductor muscle with either
      control media or cultured mesenchymal stem cells (MSCs). Blood flow recovery was
      measured using laser-Doppler [laser-Doppler perfusion imaging (LDPI) ratio]. In a
      second experiment, mice were stratified 24 h after arterial ligation before
      treatment by using a simple clinical score of the ligated leg: 1, able to flex,
      mild discoloration; 2, no flexion, mild discoloration; 3, severe discoloration;
      and 4, any necrosis. Without stratification, blood flow recovery significantly
      increased in the MSC-treated group (P < 0.05, n = 6 MSC group, n = 7 media
      group). In the experiment employing stratification, all differences between the
      groups disappeared (n = 11 MSC group, n = 10 media group; P = 0.3). Furthermore,
      we found a striking inverse correlation between clinical score on day 1 and the
      LDPI ratio on day 28 (P < 0.0001; n = 79). Anatomical confirmation of the
      disparity in preexisting collaterals was found in two different mouse strains
      using microscopic computed tomography. In conclusion, there is substantial
      interanimal variability in preexisting collateral flow, and this variability can
      importantly influence outcome. To overcome this, either animals must be
      stratified before treatment, the number of animals must be increased
      substantially, or, preferably, both.

PMID- 17189354
TI  - Borrelia burgdorferi BBA74, a periplasmic protein associated with the outer
      membrane, lacks porin-like properties.
AB  - The outer membrane of Borrelia burgdorferi, the causative agent of Lyme disease,
      contains very few integral membrane proteins, in contrast to other gram-negative
      bacteria. BBA74, a Borrelia burgdorferi plasmid-encoded protein, was proposed to
      be an integral outer membrane protein with putative porin function and designated
      as a 28-kDa outer membrane-spanning porin (Oms28). In this study, the biophysical
      properties of BBA74 and its subcellular localization were investigated. BBA74 is
      posttranslationally modified by signal peptidase I cleavage to a mature 25-kDa
      protein. The secondary structure of BBA74 as determined by circular dichroism
      spectroscopy consists of at least 78% alpha-helix with little beta-sheet
      structure. BBA74 in intact B. burgdorferi cells was insensitive to proteinase K
      digestion, and indirect immunofluorescence microscopy showed that BBA74 was not
      exposed on the cell surface. Triton X-114 extraction of outer membrane vesicle
      preparations indicated that BBA74 is not an integral membrane protein. Taken
      together, the data indicate that BBA74 is a periplasmic, outer membrane
      associated protein that lacks properties typically associated with porins.

PMID- 17189355
TI  - Biosynthetic analysis of the petrobactin siderophore pathway from Bacillus
      anthracis.
AB  - The asbABCDEF gene cluster from Bacillus anthracis is responsible for
      biosynthesis of petrobactin, a catecholate siderophore that functions in both
      iron acquisition and virulence in a murine model of anthrax. We initiated studies
      to determine the biosynthetic details of petrobactin assembly based on mutational
      analysis of the asb operon, identification of accumulated intermediates, and
      addition of exogenous siderophores to asb mutant strains. As a starting point, in
      frame deletions of each of the genes in the asb locus (asbABCDEF) were
      constructed. The individual mutations resulted in complete abrogation of
      petrobactin biosynthesis when strains were grown on iron-depleted medium.
      However, in vitro analysis showed that each asb mutant grew to a very limited
      extent as vegetative cells in iron-depleted medium. In contrast, none of the B.
      anthracis asb mutant strains were able to outgrow from spores under the same
      culture conditions. Provision of exogenous petrobactin was able to rescue the
      growth defect in each asb mutant strain. Taken together, these data provide
      compelling evidence that AsbA performs the penultimate step in the biosynthesis
      of petrobactin, involving condensation of 3,4-dihydroxybenzoyl spermidine with
      citrate to form 3,4-dihydroxybenzoyl spermidinyl citrate. As a final step, the
      data reveal that AsbB catalyzes condensation of a second molecule of 3,4
      dihydroxybenzoyl spermidine with 3,4-dihydroxybenzoyl spermidinyl citrate to form
      the mature siderophore. This work sets the stage for detailed biochemical studies
      with this unique acyl carrier protein-dependent, nonribosomal peptide synthetase
      independent biosynthetic system.

PMID- 17189356
TI  - An actin homolog of the archaeon Thermoplasma acidophilum that retains the
      ancient characteristics of eukaryotic actin.
AB  - Actin, a central component of the eukaryotic cytoskeleton, plays a crucial role
      in determining cell shape in addition to several other functions. Recently, the
      structure of the archaeal actin homolog Ta0583, isolated from the archaeon
      Thermoplasma acidophilum, which lacks a cell wall, was reported by Roeben et al.
      (J. Mol. Biol. 358:145-156, 2006). Here we show that Ta0583 assembles into
      bundles of filaments similar to those formed by eukaryotic actin. Specifically,
      Ta0583 forms a helix with a filament width of 5.5 nm and an axial repeating unit
      of 5.5 nm, both of which are comparable to those of eukaryotic actin. Eukaryotic
      actin shows a greater resemblance to Ta0583 than to bacterial MreB and ParM in
      terms of polymerization characteristics, such as the requirement for Mg(2+),
      critical concentration, and repeating unit size. Furthermore, phylogenetic
      analysis also showed a closer relationship between Ta0583 and eukaryotic actin
      than between MreB or ParM and actin. However, the low specificity of Ta0583 for
      nucleotide triphosphates indicates that Ta0583 is more primitive than eukaryotic
      actin. Taken together, our results suggest that Ta0583 retains the ancient
      characteristics of eukaryotic actin.

PMID- 17189357
TI  - Repression of the inner membrane lipoprotein NlpA by Rns in enterotoxigenic
      Escherichia coli.
AB  - The expression of the inner membrane protein NlpA is repressed by the
      enterotoxigenic Escherichia coli (ETEC) virulence regulator Rns, a member of the
      AraC/XylS family. The Rns homologs CfaD from ETEC and AggR from enteroaggregative
      E. coli also repress expression of nlpA. In vitro DNase I and potassium
      permanganate footprinting revealed that Rns binds to a site overlapping the start
      codon of nlpA, preventing RNA polymerase from forming an open complex at nlpAp. A
      second Rns binding site between positions -152 and -195 relative to the nlpA
      transcription start site is not required for repression. NlpA is not essential
      for growth of E. coli under laboratory conditions, but it does contribute to the
      biogenesis of outer membrane vesicles. As outer membrane vesicles have been shown
      to contain ETEC heat-labile toxin, the repression of nlpA may be an indirect
      mechanism through which the virulence regulators Rns and CfaD limit the release
      of toxin.

PMID- 17189358
TI  - Glucosylglycerate biosynthesis in the deepest lineage of the Bacteria:
      characterization of the thermophilic proteins GpgS and GpgP from Persephonella
      marina.
AB  - The pathway for the synthesis of glucosylglycerate (GG) in the thermophilic
      bacterium Persephonella marina is proposed based on the activities of recombinant
      glucosyl-3-phosphoglycerate (GPG) synthase (GpgS) and glucosyl-3-phosphoglycerate
      phosphatase (GpgP). The sequences of gpgS and gpgP from the cold-adapted
      bacterium Methanococcoides burtonii were used to identify the homologues in the
      genome of P. marina, which were separately cloned and overexpressed as His-tagged
      proteins in Escherichia coli. The recombinant GpgS protein of P. marina, unlike
      the homologue from M. burtonii, which was specific for GDP-glucose, catalyzed the
      synthesis of GPG from UDP-glucose, GDP-glucose, ADP-glucose, and TDP-glucose (in
      order of decreasing efficiency) and from d-3-phosphoglycerate, with maximal
      activity at 90 degrees C. The recombinant GpgP protein, like the M. burtonii
      homologue, dephosphorylated GPG and mannosyl-3-phosphoglycerate (MPG) to GG and
      mannosylglycerate, respectively, yet at high temperatures the hydrolysis of GPG
      was more efficient than that of MPG. Gel filtration indicates that GpgS is a
      dimeric protein, while GpgP is monomeric. This is the first characterization of
      genes and enzymes for the synthesis of GG in a thermophile.

PMID- 17189360
TI  - Specific binding of D1 protein degradation products to the psbAI promoter in
      Synechococcus sp. strain PCC 7942.
AB  - The D1:1 protein and its potentially occurring degradation products were
      overexpressed in Escherichia coli. Protein-DNA interaction is shown for the
      promoter region of psbAI. The D1:1 degradation products may be involved in
      transcription regulation of psbAI by binding in the promoter region.
      Additionally, C-terminal fragments of the D1 protein bind to a sequence with
      similarity to isiB, a gene which encodes a flavodoxin-like protein.

PMID- 17189359
TI  - The pio operon is essential for phototrophic Fe(II) oxidation in Rhodopseudomonas
      palustris TIE-1.
AB  - Phototrophic Fe(II)-oxidizing bacteria couple the oxidation of ferrous iron
      [Fe(II)] to reductive CO(2) fixation by using light energy, but until recently,
      little has been understood about the molecular basis for this process. Here we
      report the discovery, with Rhodopseudomonas palustris TIE-1 as a model organism,
      of a three-gene operon, designated the pio operon (for phototrophic iron
      oxidation), that is necessary for phototrophic Fe(II) oxidation. The first gene
      in the operon, pioA, encodes a c-type cytochrome that is upregulated under Fe(II)
      grown conditions. PioA contains a signal sequence and shares homology with MtrA,
      a decaheme c-type cytochrome from Shewanella oneidensis MR-1. The second gene,
      pioB, encodes a putative outer membrane beta-barrel protein. PioB is a homologue
      of MtrB from S. oneidensis MR-1. The third gene, pioC, encodes a putative high
      potential iron sulfur protein (HiPIP) with a twin-arginine translocation (Tat)
      signal sequence and is similar to the putative Fe(II) oxidoreductase (Iro) from
      Acidithiobacillus ferrooxidans. Like PioA, PioB and PioC appear to be secreted
      proteins. Deletion of the pio operon results in loss of Fe(II) oxidation activity
      and growth on Fe(II). Complementation studies confirm that the phenotype of this
      mutant is due to loss of the pio genes. Deletion of pioA alone results in loss of
      almost all Fe(II) oxidation activity; however, deletion of either pioB or pioC
      alone results in only partial loss of Fe(II) oxidation activity. Together, these
      results suggest that proteins encoded by the pio operon are essential and
      specific for phototrophic Fe(II) oxidation in R. palustris TIE-1.

PMID- 17189361
TI  - On torque and tumbling in swimming Escherichia coli.
AB  - Bacteria swim by rotating long thin helical filaments, each driven at its base by
      a reversible rotary motor. When the motors of peritrichous cells turn
      counterclockwise (CCW), their filaments form bundles that drive the cells
      forward. We imaged fluorescently labeled cells of Escherichia coli with a high
      speed charge-coupled-device camera (500 frames/s) and measured swimming speeds,
      rotation rates of cell bodies, and rotation rates of flagellar bundles. Using
      cells stuck to glass, we studied individual filaments, stopping their rotation by
      exposing the cells to high-intensity light. From these measurements we calculated
      approximate values for bundle torque and thrust and body torque and drag, and we
      estimated the filament stiffness. For both immobilized and swimming cells, the
      motor torque, as estimated using resistive force theory, was significantly lower
      than the motor torque reported previously. Also, a bundle of several flagella
      produced little more torque than a single flagellum produced. Motors driving
      individual filaments frequently changed directions of rotation. Usually, but not
      always, this led to a change in the handedness of the filament, which went
      through a sequence of polymorphic transformations, from normal to semicoiled to
      curly 1 and then, when the motor again spun CCW, back to normal. Motor reversals
      were necessary, although not always sufficient, to cause changes in filament
      chirality. Polymorphic transformations among helices having the same handedness
      occurred without changes in the sign of the applied torque.

PMID- 17189362
TI  - Characterization of a novel D-lyxose isomerase from Cohnella laevoribosii RI-39
      sp. nov.
AB  - A newly isolated bacterium, Cohnella laevoribosii RI-39, could grow in a defined
      medium with L-ribose as the sole carbon source. A 21-kDa protein isomerizing L
      ribose to L-ribulose, as well as D-lyxose to D-xylulose, was purified to
      homogeneity from this bacterium. Based on the N-terminal and internal amino acid
      sequences of the purified enzyme obtained by N-terminal sequencing and
      quantitative time of flight mass spectrometry-mass spectrometry analyses, a 549
      bp gene (lyxA) encoding D-lyxose (L-ribose) isomerase was cloned and expressed in
      Escherichia coli. The purified endogenous enzyme and the recombinant enzyme
      formed homodimers that were activated by Mn(2+). C. laevoribosii D-lyxose (L
      ribose) isomerase (CLLI) exhibits maximal activity at pH 6.5 and 70 degrees C in
      the presence of Mn(2+) for D-lyxose and L-ribose, and its isoelectric point (pI)
      is 4.2 (calculated pI, 4.9). The enzyme is specific for D-lyxose, L-ribose, and D
      mannose, with apparent K(m) values of 22.4 +/- 1.5 mM, 121.7 +/- 10.8 mM, and
      34.0 +/- 1.1 mM, respectively. The catalytic efficiencies (k(cat)/K(m)) of CLLI
      were 84.9 +/- 5.8 mM(-1) s(-1) for D-lyxose (V(max), 5,434.8 U mg(-1)), 0.2 mM(
      1) s(-1) for L-ribose (V(max), 75.5 +/- 6.0 U mg(-1)), and 1.4 +/- 0.1 mM(-1) s(
      1) for D-mannose (V(max), 131.8 +/- 7.4 U mg(-1)). The ability of lyxA to permit
      E. coli cells to grow on D-lyxose and L-ribose and homology searches of other
      sugar-related enzymes, as well as previously described sugar isomerases, suggest
      that CLLI is a novel type of rare sugar isomerase.

PMID- 17189363
TI  - A novel protein, TtpC, is a required component of the TonB2 complex for specific
      iron transport in the pathogens Vibrio anguillarum and Vibrio cholerae.
AB  - Active transport across the outer membrane in gram-negative bacteria requires the
      energy that is generated by the proton motive force in the inner membrane. This
      energy is transduced to the outer membrane by the TonB protein in complex with
      the proteins ExbB and ExbD. In the pathogen Vibrio anguillarum we have identified
      two TonB systems, TonB1 and TonB2, the latter is used for ferric-anguibactin
      transport and is transcribed as part of an operon that consists of orf2, exbB2,
      exbD2, and tonB2. This cluster was identified by a polar transposon insertion in
      orf2 that resulted in a strain deficient for ferric-anguibactin transport. Only
      the entire cluster (orf2, exbB2, exbD2 and tonB2) could complement for ferric
      anguibactin transport, while just the exbB2, exbD2, and tonB2 genes were unable
      to restore transport. This suggests an essential role for this Orf2, designated
      TtpC, in TonB2-mediated transport in V. anguillarum. A similar gene cluster
      exists in V. cholerae, i.e., with the homologues of ttpC-exbB2-exbD2-tonB2, and
      we demonstrate that TtpC from V. cholerae also plays a role in the TonB2-mediated
      transport of enterobactin in this human pathogen. Furthermore, we also show that
      in V. anguillarum the TtpC protein is found as part of a complex that might also
      contain the TonB2, ExbB2, and ExbD2 proteins. This novel component of the TonB2
      system found in V. anguillarum and V. cholerae is perhaps a general feature in
      bacteria harboring the Vibrio-like TonB2 system.

PMID- 17189364
TI  - Characterization of ResDE-dependent fnr transcription in Bacillus subtilis.
AB  - The ResD-ResE signal transduction system is required for transcription of genes
      involved in aerobic and anaerobic respiration in Bacillus subtilis.
      Phosphorylated ResD (ResD approximately P) interacts with target DNA to activate
      transcription. A strong sequence similarity was detected in promoter regions of
      some ResD-controlled genes including fnr and resA. Single-base substitutions in
      the fnr and resA promoters were performed to determine a ResD-binding sequence.
      DNase I footprinting analysis indicated that ResD approximately P itself does not
      bind to fnr, but interaction of ResD approximately P with the C-terminal domain
      of the alpha subunit (alphaCTD) of RNA polymerase (RNAP) facilitates cooperative
      binding of ResD approximately P and RNAP, thereby increasing fnr transcription
      initiation. Consistent with this result, amino acid substitutions in alphaCTD,
      such as Y263A, K267A, A269I, or N290A, sharply reduced fnr transcription in vivo,
      and the K267A alphaCTD protein, unlike the wild-type protein, did not increase
      ResD approximately P binding to the fnr promoter. Amino acid residues of alphaCTD
      required for ResD-dependent fnr transcription, with the exception of N290, which
      may interact with DNA, constitute a distinct surface, suggesting that these
      residues likely interact with ResD approximately P.

PMID- 17189365
TI  - Functional analysis of nine putative chemoreceptor proteins in Sinorhizobium
      meliloti.
AB  - The genome of the symbiotic soil bacterium Sinorhizobium meliloti contains eight
      genes coding for methyl-accepting chemotaxis proteins (MCPs) McpS to McpZ and one
      gene coding for a transducer-like protein, IcpA. Seven of the MCPs are localized
      in the cytoplasmic membrane via two membrane-spanning regions, whereas McpY and
      IcpA lack such hydrophobic regions. The periplasmic regions of McpU, McpV, and
      McpX contain the small-ligand-binding domain Cache. In addition, McpU possesses
      the ligand-binding domain TarH. By probing gene expression with lacZ fusions, we
      have identified mcpU and mcpX as being highly expressed. Deletion of any one of
      the receptor genes caused impairments in the chemotactic response toward most
      organic acids, amino acids, and sugars in a swarm plate assay. The data imply
      that chemoreceptor proteins in S. meliloti can sense more than one class of
      carbon source and suggest that many or all receptors work as an ensemble. Tactic
      responses were virtually eliminated for a strain lacking all nine receptor genes.
      Capillary assays revealed three important sensors for the strong attractant
      proline: McpU, McpX, and McpY. Receptor deletions variously affected free
      swimming speed and attractant-induced chemokinesis. Noticeably, cells lacking
      mcpU were swimming 9% slower than the wild-type control. We infer that McpU
      inhibits the kinase activity of CheA in the absence of an attractant. Cells
      lacking one of the two soluble receptors were impaired in chemokinetic
      proficiency by more than 50%. We propose that the internal sensors, IcpA and the
      PAS domain containing McpY, monitor the metabolic state of S. meliloti.

PMID- 17189366
TI  - YjjG, a dUMP phosphatase, is critical for thymine utilization by Escherichia coli
      K-12.
AB  - Exogenous thymine must be converted to thymidine to enable a thyA (thymidylate
      synthase) mutant to grow. The deoxyribose in the thymidine comes from dUMP, which
      must first be dephosphorylated. The nucleotidase YjjG is critical for this step.
      A yjjG thyA mutant cannot use thymine for growth on a glucose minimal medium.

PMID- 17189367
TI  - Intracellular copper does not catalyze the formation of oxidative DNA damage in
      Escherichia coli.
AB  - Because copper catalyzes the conversion of H(2)O(2) to hydroxyl radicals in
      vitro, it has been proposed that oxidative DNA damage may be an important
      component of copper toxicity. Elimination of the copper export genes, copA, cueO,
      and cusCFBA, rendered Escherichia coli sensitive to growth inhibition by copper
      and provided forcing circumstances in which this hypothesis could be tested. When
      the cells were grown in medium supplemented with copper, the intracellular copper
      content increased 20-fold. However, the copper-loaded mutants were actually less
      sensitive to killing by H(2)O(2) than cells grown without copper supplementation.
      The kinetics of cell death showed that excessive intracellular copper eliminated
      iron-mediated oxidative killing without contributing a copper-mediated component.
      Measurements of mutagenesis and quantitative PCR analysis confirmed that copper
      decreased the rate at which H(2)O(2) damaged DNA. Electron paramagnetic resonance
      (EPR) spin trapping showed that the copper-dependent H(2)O(2) resistance was not
      caused by inhibition of the Fenton reaction, for copper-supplemented cells
      exhibited substantial hydroxyl radical formation. However, copper EPR
      spectroscopy suggested that the majority of H(2)O(2)-oxidizable copper is located
      in the periplasm; therefore, most of the copper-mediated hydroxyl radical
      formation occurs in this compartment and away from the DNA. Indeed, while E. coli
      responds to H(2)O(2) stress by inducing iron sequestration proteins, H(2)O(2)
      stressed cells do not induce proteins that control copper levels. These
      observations do not explain how copper suppresses iron-mediated damage. However,
      it is clear that copper does not catalyze significant oxidative DNA damage in
      vivo; therefore, copper toxicity must occur by a different mechanism.

PMID- 17189368
TI  - Growth phase regulation of Vibrio cholerae RTX toxin export.
AB  - Vibrio cholerae, the causative agent of the severe diarrheal disease cholera,
      secretes several "accessory" toxins, including RTX toxin, which causes the cross
      linking of the actin cytoskeleton. RTX toxin is exported to the extracellular
      milieu by an atypical type I secretion system (T1SS), and we previously noted
      that RTX-associated activity is detectable only in supernatant fluids from log
      phase cultures. Here, we investigate the mechanisms for regulating RTX toxin
      activity in supernatant fluids. We find that exported proteases are capable of
      destroying RTX activity and may therefore play a role in the growth phase
      regulation of toxin activity. We determined that the absence of RTX toxin in
      stationary-phase culture supernatant fluids is also due to a lack of toxin
      secretion and not attributable to solely proteolytic degradation. We ascertained
      that the T1SS apparatus is regulated at the transcriptional level by growth phase
      control that is independent of quorum sensing, unlike other virulence factors of
      V. cholerae. Additionally, in stationary-phase cultures, all RTX toxin activity
      is associated with bacterial membranes or outer membrane vesicles.

PMID- 17189369
TI  - Mutations of the act promoter in Myxococcus xanthus.
AB  - Mutations within the -12 and -24 elements provide evidence that the act promoter
      is recognized by sigma-54 RNA polymerase. Deletion of the -20 base pair, which
      lies between the two conserved elements of sigma-54 promoters, decreased
      expression by 90%. In addition, mutation of a potential enhancer sequence, around
      -120, led to an 80% reduction in act gene expression. actB, the second gene in
      the act operon, encodes a sigma-54 activator protein that is proposed to be an
      enhancer-binding protein for the act operon. All act genes, actA to actE, are
      expressed together and constitute an operon, because an in-frame deletion of actB
      decreased expression of actA and actE to the same extent. After an initially slow
      phase of act operon expression, which depends on FruA, there is a rapid phase.
      The rapid phase is shown to be due to the activation of the operon expression by
      ActB, which completes a positive feedback loop. That loop appears to be nested
      within a larger positive loop in which ActB is activated by the C signal via
      ActA, and the act operon activates transcription of the csgA gene. We propose
      that, as cells engage in more C signaling, positive feedback raises the number of
      C-signal molecules per cell and drives the process of fruiting body development
      forward.

PMID- 17189372
TI  - Bacteroides fragilis synthesizes a DNA invertase affecting both a local and a
      distant region.
AB  - The activity of a fourth conserved tyrosine site-specific recombinase (Tsr) of
      Bacteroides fragilis was characterized. Its gene, tsr19, is adjacent to mpi,
      encoding the global DNA invertase regulating capsular polysaccharide
      biosynthesis. Unlike the other described Tsrs of B. fragilis, Tsr19 brings about
      inversion of two DNA regions, one local and one located distantly.

PMID- 17189371
TI  - The fox operon from Rhodobacter strain SW2 promotes phototrophic Fe(II) oxidation
      in Rhodobacter capsulatus SB1003.
AB  - Anoxygenic photosynthesis based on Fe(II) is thought to be one of the most
      ancient forms of metabolism and is hypothesized to represent a transition step in
      the evolution of oxygenic photosynthesis. However, little is known about the
      molecular basis of this process because, until recently (Y. Jiao and D. K.
      Newman, J. Bacteriol. 189:1765-1773, 2007), most phototrophic Fe(II)-oxidizing
      bacteria have been genetically intractable. In this study, we circumvented this
      problem by taking a heterologous-complementation approach to identify a three
      gene operon (the foxEYZ operon) from Rhodobacter sp. strain SW2 that confers
      enhanced light-dependent Fe(II) oxidation activity when expressed in its
      genetically tractable relative Rhodobacter capsulatus SB1003. The first gene in
      this operon, foxE, encodes a c-type cytochrome with no significant similarity to
      other known proteins. Expression of foxE alone confers significant light
      dependent Fe(II) oxidation activity on SB1003, but maximal activity is achieved
      when foxE is expressed with the two downstream genes foxY and foxZ. In SW2, the
      foxE and foxY genes are cotranscribed in the presence of Fe(II) and/or hydrogen,
      with foxZ being transcribed only in the presence of Fe(II). Sequence analysis
      predicts that foxY encodes a protein containing the redox cofactor
      pyrroloquinoline quinone and that foxZ encodes a protein with a transport
      function. Future biochemical studies will permit the localization and function of
      the Fox proteins in SW2 to be determined.

PMID- 17189370
TI  - Nitric oxide in chemostat-cultured Escherichia coli is sensed by Fnr and other
      global regulators: unaltered methionine biosynthesis indicates lack of S
      nitrosation.
AB  - We previously elucidated the global transcriptional responses of Escherichia coli
      to the nitrosating agent S-nitrosoglutathione (GSNO) in both aerobic and
      anaerobic chemostats, demonstrated the expression of nitric oxide (NO)-protective
      mechanisms, and obtained evidence of critical thiol nitrosation. The present
      study was the first to examine the transcriptome of NO-exposed E. coli in a
      chemostat. Using identical conditions, we compared the GSNO stimulon with the
      stimulon of NO released from two NO donor compounds {3-[2-hydroxy-1-(1-methyl
      ethyl)-2-nitrosohydrazino]-1-propanamine (NOC-5) and 3-(2-hydroxy-1-methyl-2
      nitrosohydrazino)-N-methyl-1-propanamine (NOC-7)} simultaneously and demonstrated
      that there were marked differences in the transcriptional responses to these
      distinct nitrosative stresses. Exposure to NO did not induce met genes,
      suggesting that, unlike GSNO, NO does not elicit homocysteine S nitrosation and
      compensatory increases in methionine biosynthesis. After entry into cells,
      exogenous methionine provided protection from GSNO-mediated killing but not from
      NO-mediated killing. Anaerobic exposure to NO led to up-regulation of multiple
      Fnr-repressed genes and down-regulation of Fnr-activated genes, including nrfA,
      which encodes cytochrome c nitrite reductase, providing strong evidence that
      there is NO inactivation of Fnr. Other global regulators apparently affected by
      NO were IscR, Fur, SoxR, NsrR, and NorR. We tried to identify components of the
      NorR regulon by performing a microarray comparison of NO-exposed wild-type and
      norR mutant strains; only norVW, encoding the NO-detoxifying flavorubredoxin and
      its cognate reductase, were unambiguously identified. Mutation of norV or norR
      had no effect on E. coli survival in mouse macrophages. Thus, GSNO (a nitrosating
      agent) and NO have distinct cellular effects; NO more effectively interacts with
      global regulators that mediate adaptive responses to nitrosative stress but does
      not affect methionine requirements arising from homocysteine nitrosation.

PMID- 17189373
TI  - Salmonella: from pathogenesis to therapeutics.

PMID- 17189375
TI  - Characterization of colony morphology variants isolated from Streptococcus
      pneumoniae biofilms.
AB  - In this study, we report the isolation of colony morphology variants from
      Streptococcus pneumoniae serotype 3 biofilms. The colony variants differed in
      colony size (large, medium, and small) and their mucoid appearance on blood agar.
      The small nonmucoid variant (SCV) emerged during the initial attachment stage of
      S. pneumoniae biofilm formation and dominated over the course of biofilm growth.
      Mucoid variants appeared at later biofilm developmental stages. The reduction in
      colony size/mucoidy correlated with a decrease in capsule production and an
      increase in initial attachment. The large mucoid variant formed flat unstructured
      biofilms, failed to aggregate in liquid culture, and adhered poorly to solid
      surfaces. In contrast, SCVs autoaggregated in liquid culture, hyperadhered to
      solid surfaces, and formed biofilms with significant three-dimensional structure,
      mainly in the form of microcolonies. The variants showed similar antibiotic
      resistance/susceptibility based on a modified Kirby-Bauer test and when grown as
      biofilms. However, antimicrobial treatment of S. pneumoniae biofilms altered the
      colony variant's distribution and mainly affected the most interior areas of
      biofilm microcolonies. To further explore the nature of the variants, the capsule
      biosynthetic operon (cps3DSUM) was explored in greater detail. The genetic
      analysis indicated that the emergence of nonmucoid variants was due to a deletion
      comprising cps3DSU as well as additional genes upstream of the cps3 operon.
      Overall, our findings suggest that in vitro biofilm formation of S. pneumoniae
      serotype 3 coincides with the emergence of colony variants with distinct
      genotypic and phenotypic characteristics.

PMID- 17189374
TI  - The alternative sigma factor sigmaH is required for toxin gene expression by
      Bacillus anthracis.
AB  - Expression of the structural genes for the anthrax toxin proteins is coordinately
      controlled by host-related signals, such as elevated CO(2), and the trans-acting
      positive regulator AtxA. In addition to these requirements, toxin gene expression
      is under growth phase regulation. The transition state regulator AbrB represses
      atxA expression to influence toxin synthesis. During the late exponential phase
      of growth, when AbrB levels begin to decrease, toxin synthesis increases. Here we
      report that toxin gene expression also requires the presence of sigH, a gene
      encoding the RNA polymerase sigma factor associated with development in Bacillus
      subtilis. In the well-studied B. subtilis system, sigma(H) is required for
      sporulation and other post-exponential-phase processes and is part of a feedback
      control pathway for abrB expression. Our data indicate that a Bacillus anthracis
      sigH-null mutant is asporogenous and toxin deficient. Yet the sigma factor is
      required for toxin gene expression in a manner that is independent of the pathway
      leading to post-exponential-phase gene expression. Sigma(H) positively controls
      atxA in an AbrB-independent manner. These findings, combined with previous
      observations, suggest that the steady-state level of atxA expression is critical
      for optimal toxin gene transcription. We propose a model whereby, under toxin
      inducing growth conditions, control of toxin gene expression is fine-tuned by the
      independent effects of sigma(H) and AbrB on the expression of atxA.

PMID- 17189376
TI  - Weak rolling adhesion enhances bacterial surface colonization.
AB  - Bacterial adhesion to and subsequent colonization of surfaces are the first steps
      toward forming biofilms, which are a major concern for implanted medical devices
      and in many diseases. It has generally been assumed that strong irreversible
      adhesion is a necessary step for biofilm formation. However, some bacteria, such
      as Escherichia coli when binding to mannosylated surfaces via the adhesive
      protein FimH, adhere weakly in a mode that allows them to roll across the
      surface. Since single-point mutations or even increased shear stress can switch
      this FimH-mediated adhesion to a strong stationary mode, the FimH system offers a
      unique opportunity to investigate the role of the strength of adhesion
      independently from the many other factors that may affect surface colonization.
      Here we compare levels of surface colonization by E. coli strains that differ in
      the strength of adhesion as a result of flow conditions or point mutations in
      FimH. We show that the weak rolling mode of surface adhesion can allow a more
      rapid spreading during growth on a surface in the presence of fluid flow. Indeed,
      an attempt to inhibit the adhesion of strongly adherent bacteria by blocking
      mannose receptors with a soluble inhibitor actually increased the rate of surface
      colonization by allowing the bacteria to roll. This work suggests that (i) a
      physiological advantage to the weak adhesion demonstrated by commensal variants
      of FimH bacteria may be to allow rapid surface colonization and (ii) antiadhesive
      therapies intended to prevent biofilm formation can have the unintended effect of
      enhancing the rate of surface colonization.

PMID- 17189377
TI  - Role of mRNA stability in growth phase regulation of gene expression in the group
      A streptococcus.
AB  - The impressive disease spectrum of Streptococcus pyogenes (the group A
      streptococcus [GAS]) is believed to be determined by its ability to modify gene
      expression in response to environmental stimuli. Virulence gene expression is
      controlled tightly by several different transcriptional regulators in this
      organism. In addition, expression of most, if not all, GAS genes is determined by
      a global mechanism dependent on growth phase. To begin an analysis of growth
      phase regulation, we compared the transcriptome 2 h into stationary phase to that
      in late exponential phase of a serotype M3 GAS strain. We identified the arc
      transcript as more abundant in stationary phase in addition to the sag and sda
      transcripts that had been previously identified. We found that in stationary
      phase, the stability of sagA, sda, and arcT transcripts increased dramatically.
      We found that polynucleotide phosphorylase (PNPase [encoded by pnpA]) is rate
      limiting for decay of sagA and sda transcripts in late exponential phase, since
      the stability of these mRNAs was greater in a pnpA mutant, while stability of
      control mRNAs was unaffected by this mutation. Complementation restored the wild
      type decay rate. Furthermore, in a pnpA mutant, the sagA mRNA appeared to be full
      length, as determined by Northern hybridization. It seems likely that mRNAs
      abundant in stationary phase are insensitive to the normal decay enzyme(s) and
      instead require PNPase for this process. It is possible that PNPase activity is
      limited in stationary phase, allowing persistence of these important virulence
      factor transcripts at this phase of growth.

PMID- 17189378
TI  - Rapid and cost-effective polymorphism identification and genotyping using
      restriction site associated DNA (RAD) markers.
AB  - Restriction site associated DNA (RAD) tags are a genome-wide representation of
      every site of a particular restriction enzyme by short DNA tags. Most organisms
      segregate large numbers of DNA sequence polymorphisms that disrupt restriction
      sites, which allows RAD tags to serve as genetic markers spread at a high density
      throughout the genome. Here, we demonstrate the applicability of RAD markers for
      both individual and bulk-segregant genotyping. First, we show that these markers
      can be identified and typed on pre-existing microarray formats. Second, we
      present a method that uses RAD marker DNA to rapidly produce a low-cost
      microarray genotyping resource that can be used to efficiently identify and type
      thousands of RAD markers. We demonstrate the utility of the former approach by
      using a tiling path array for the fruit fly to map a recombination breakpoint,
      and the latter approach by creating and using an enriched RAD marker array for
      the threespine stickleback. The high number of RAD markers enabled localization
      of a previously identified region, as well as a second region also associated
      with the lateral plate phenotype. Taken together, our results demonstrate that
      RAD markers, and the method to develop a RAD marker microarray resource, allow
      high-throughput, high-resolution genotyping in both model and nonmodel systems.

PMID- 17189380
TI  - Ubiquitin hubs in oncogenic networks.
AB  - Ubiquitin is an important regulator of diverse biological functions including
      cell cycle progression, apoptosis, cell proliferation, and DNA damage responses.
      Crucial proteins involved in the control of such diverse functions are modified
      by ubiquitin and are frequently altered during oncogenesis. Here, we define such
      proteins as key-nodes regulated by ubiquitin, discuss examples of their oncogenic
      aberrations, and indicate how pharmacologic manipulation of such molecular hubs
      might improve anticancer therapy.

PMID- 17189379
TI  - Improving gene annotation using peptide mass spectrometry.
AB  - Annotation of protein-coding genes is a key goal of genome sequencing projects.
      In spite of tremendous recent advances in computational gene finding,
      comprehensive annotation remains a challenge. Peptide mass spectrometry is a
      powerful tool for researching the dynamic proteome and suggests an attractive
      approach to discover and validate protein-coding genes. We present algorithms to
      construct and efficiently search spectra against a genomic database, with no
      prior knowledge of encoded proteins. By searching a corpus of 18.5 million tandem
      mass spectra (MS/MS) from human proteomic samples, we validate 39,000 exons and
      11,000 introns at the level of translation. We present translation-level evidence
      for novel or extended exons in 16 genes, confirm translation of 224 hypothetical
      proteins, and discover or confirm over 40 alternative splicing events.
      Polymorphisms are efficiently encoded in our database, allowing us to observe
      variant alleles for 308 coding SNPs. Finally, we demonstrate the use of mass
      spectrometry to improve automated gene prediction, adding 800 correct exons to
      our predictions using a simple rescoring strategy. Our results demonstrate that
      proteomic profiling should play a role in any genome sequencing project.

PMID- 17189381
TI  - Use of an aggressive MCF-7 cell line variant, TMX2-28, to study cell invasion in
      breast cancer.
AB  - An estrogen receptor-negative variant of the MCF-7 breast cancer cell line, TMX2
      28, was used as a model in which to study breast cancer cell invasion. Using a
      reconstituted basement membrane (Matrigel) assay to evaluate cell invasion, we
      determined that TMX2-28 cells are more invasive than MCF-7 cells and that the
      invasiveness of TMX2-28 is similar to that of the aggressive MDA-MB-231 breast
      cancer cell line. TMX2-28 cells displayed a rounded, epithelial cell-like
      morphology, suggesting an amoeboid mode of cell invasion, in contrast to the
      mesenchymal mode of invasion characteristic of spindle-shaped, fibroblast-like
      MDA-MB-231 cells. Using real-time reverse transcription-PCR, we found that
      mitogen-inducible gene 2 (MIG2) is expressed at a 17-fold higher level in TMX2-28
      cells than in nonaggressive MCF-7 cells and that MIG2 mRNA levels are low in the
      nontumorigenic human mammary epithelial cell line, 184. We determined that MIG2
      plays a role in cell invasion by using small interfering RNA (siRNA) to suppress
      the expression of MIG2 mRNA levels in TMX2-28 cells. TMX2-28 cell invasion was
      reduced by 48% when the cells were transfected with siRNAs targeting MIG2,
      relative to cells transfected with siRNAs against glyceraldehyde-3-phosphate
      dehydrogenase. Finally, MIG2 expression was evaluated in reductive mammoplasty
      and breast tumor tissue. Although all 21 normal tissues from reduction
      mammoplasty showed immunoreactivity for MIG2, ranging from weak (62%) to strong
      (24%), only half of the 34 formalin-fixed breast tumors showed immunoreactivity
      for MIG2. Of these 17 positive cases, 10 were considered to overexpress MIG2
      (moderate to strong staining). Examination of 30 frozen breast tumors supported
      the finding that MIG2 is overexpressed in a subset of breast cancers. We suggest
      that MIG2's normal regulation and function are disrupted in breast cancer.

PMID- 17189382
TI  - Expression of the receptor tyrosine kinase Tie2 in neoplastic glial cells is
      associated with integrin beta1-dependent adhesion to the extracellular matrix.
AB  - The abnormal function of tyrosine kinase receptors is a hallmark of malignant
      gliomas. Tie2 receptor tyrosine kinase is a specific endothelial cell receptor
      whose function is positively regulated by angiopoietin 1 (Ang1). Recently, Tie2
      has also been found in the nonvascular compartment of several tumors, including
      leukemia as well as breast, gastric, and thyroid cancers. There is, however,
      little information on the function of the Ang1/Tie2 pathway in the non-stromal
      cells within human tumors. We found that surgical glioblastoma specimens
      contained a subpopulation of Tie2+/CD31- and Tie2+/GFAP+ cells, suggesting that
      Tie2 is indeed expressed outside the vascular compartment of gliomas.
      Furthermore, analysis of a tissue array consisting of 116 human glioma samples
      showed that Tie2 expression in the neoplastic glial cells was significantly
      associated with progression from a lower to higher grade. Importantly, Ang1
      stimulation of Tie2+ glioma cells resulted in increased adherence of the cells to
      collagen I and IV, suggesting that Tie2 regulates glioma cell adhesion to the
      extracellular matrix. Conversely, the down-regulation of Tie2 levels by small
      interference RNA or the addition of soluble Tie2 abrogated the Ang1-mediated
      effect on cell adhesion. In studying the expression of cell adhesion molecules,
      we found that Tie2 activation was related to the up-regulation of integrin beta1
      levels and the formation of focal adhesions. These results, together with the
      reported fact that malignant gliomas express high levels of Ang1, suggest the
      existence of an autocrine loop in malignant gliomas and that a Tie2-dependent
      pathway modulates cell-to-extracellular matrix adhesion, providing new insights
      into the highly infiltrative phenotype of human gliomas.

PMID- 17189383
TI  - Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas.
AB  - Receptor tyrosine kinase aberrations are implicated in the genesis of gliomas. We
      investigated expression and amplification of KIT, PDGFRA, VEGFR2, and EGFR in 87
      gliomas consisting of astrocytomas, anaplastic astrocytomas, oligodendrogliomas,
      or oligoastrocytomas in tumor samples collected at the time of the diagnosis and
      in samples of the same tumors at tumor recurrence. Gene amplifications were
      investigated using either chromogenic in situ hybridization or fluorescence in
      situ hybridization, and protein expression using immunohistochemistry. In samples
      collected at glioma diagnosis, KIT and PDGFRA amplifications were more frequent
      in anaplastic astrocytomas than in astrocytomas, oligodendrogliomas, and
      oligoastrocytomas [28% versus 5% (P = 0.012) and 33% versus 2% (P = 0.0008),
      respectively]. VEGFR2 amplifications occurred in 6% to 17% of the gliomas at
      diagnosis, and EGFR amplifications in 0% to 12%. Amplified KIT was more
      frequently present in recurrent gliomas than in newly diagnosed gliomas (P =
      0.0066). KIT amplification was associated with KIT protein expression and with
      presence of PDGFRA and EGFR amplifications both at the time of the first glioma
      diagnosis and at tumor recurrence, and with VEGFR2 amplification at tumor
      recurrence. Three (4%) primary gliomas and 10 (14%) recurrent gliomas that were
      evaluable for coamplification of KIT, PDGFRA, and VEGFR2 showed amplification of
      at least two of these genes; the amplicon contained amplified KIT in all 13
      cases. In conclusion, besides glioblastoma, amplified KIT, PDGFRA, and VEGFR may
      also occur in lower-grade gliomas and in their recurrent tumors. It is currently
      not known whether specific tyrosine kinase inhibitors are effective in the
      treatment of such gliomas.

PMID- 17189384
TI  - Fbw7 isoform interaction contributes to cyclin E proteolysis.
AB  - The ubiquitin proteasome system plays important roles in regulating cell growth
      and proliferation. Many proteins that function in ubiquitin-mediated destruction
      have been linked to tumorigenesis. The putative tumor-suppressor protein Fbw7
      (hAgo/hCdc4) is a specificity factor for the Skp1-Cul1-F-box protein ubiquitin
      ligase complex and targets a number of proto-oncogene products for ubiquitin
      mediated destruction, including the cell cycle regulator cyclin E. In mammals,
      there are three splice variants of Fbw7 that use distinct first exons, resulting
      in proteins that have unique NH(2) termini but are otherwise identical. Here, we
      show that the Fbw7 splice variants interact with each other through an NH(2)
      terminal region common to all of the Fbw7 isoforms. Other F-box proteins have
      been shown to regulate substrate binding or turnover by forming homodimeric or
      heterodimeric complexes, which are dependent on a sequence motif called the D
      domain. Fbw7 and its orthologues exhibit significant sequence similarity to such
      F-box proteins, including the D domain. Fbw7 mutants that lack the region
      encompassing the D domain fail to bind other Fbw7 isoforms, despite being
      properly localized and binding both cyclin E and Skp1. Finally, we show the
      functional significance of this region as mutants lacking the NH(2)-terminal
      region involved in Fbw7 binding exhibit reduced rates of cyclin E protein
      turnover, indicating that Fbw7 isoform interaction is important for the
      efficiency of cyclin E turnover. Overall, this study contributes to the current
      understanding of the regulation of the Fbw7 tumor-suppressor protein.

PMID- 17189385
TI  - Nuclear factor-kappaB p65 inhibits mitogen-activated protein kinase signaling
      pathway in radioresistant breast cancer cells.
AB  - The molecular mechanism by which tumor cells increase their resistance to
      therapeutic radiation remains to be elucidated. We have previously reported that
      activation of nuclear factor-kappaB (NF-kappaB) is causally associated with the
      enhanced cell survival of MCF+FIR cells derived from breast cancer MCF-7 cells
      after chronic exposure to fractionated ionizing radiation. The aim of the present
      study was to reveal the context of NF-kappaB pathways in the adaptive
      radioresistance. Using cell lines isolated from MCF+FIR populations, we found
      that the elevated NF-kappaB activity was correlated with enhanced clonogenic
      survival, and increased NF-kappaB subunit p65 levels were associated with a
      decrease in phosphorylation of mitogen-activated protein kinase/extracellular
      signal-regulated kinase (ERK) kinase (MEK)/ERK in all radioresistant MCF+FIR cell
      lines. Further irradiation with 30 fractions of radiation also inhibited MEK/ERK
      phosphorylation in paired cell lines of MCF+FIR and parental MCF-7 cells.
      Activation of ataxia-telangiectasia mutated (ATM) protein, a sensor to radiation
      induced DNA damage, was elevated with increased interaction with NF-kappaB
      subunits p65 and p50. The interaction between p65 and MEK was also enhanced in
      the presence of activated ATM. In contrast, both interaction and nuclear
      translocation of p65/ERK were reduced. Inhibition of NF-kappaB by overexpression
      of mutant IkappaB increased ERK phosphorylation. In addition, MEK/ERK inhibitor
      (PD98059) reduced the interaction between p65 and ERK. Taken together, these
      results suggest that NF-kappaB inhibits ERK activation to enhance cell survival
      during the development of tumor adaptive radioresistance.

PMID- 17189386
TI  - Bub1 up-regulation and hyperphosphorylation promote malignant transformation in
      SV40 tag-induced transgenic mouse models.
AB  - Rodents do not naturally develop prostate cancer. Currently, most widely used
      genetically engineered mouse prostate cancer models use SV40 T/tag oncogene. To
      understand the mechanism underlying prostate cancer development in transgenic and
      knock-in SV40 Tag mouse models, we did cDNA microarray analyses, comparing gene
      expression profiles of prostate cancer tissues from early-, late-, and advance
      stage androgen-independent prostate cancers. Of the 67 genes that were up
      regulated by > or = 10-fold, 40 are known to be required for chromosome
      stability. In particular, the spindle checkpoint component Bub1 was persistently
      up-regulated from early to advanced androgen-independent prostate cancer lesions.
      Significantly, Bub1, which is required for accurate chromosome segregation during
      mitosis, has recently been reported to bind SV40 Tag. Consistent with a spindle
      checkpoint defect, flow cytometry experiments indicate that advanced androgen
      independent prostate cancer tumors exhibit aneuploidy, along with up-regulation
      of levels of both Bub1 mRNA and Bub1 protein or hyperphosphorylation.
      Importantly, up-regulation and hyperphosphorylation of Bub1 were also observed in
      established human prostate cancer cell lines and in clinical studies.
      Furthermore, analysis of human prostate cancer lines showed impaired spindle
      checkpoint function and endoreduplication following exposure to spindle toxins.
      Small interfering RNA-mediated repression of Bub1 in the human prostate cancer
      line PC-3 restrained cell proliferation, an effect mimicked by inhibition of
      mitogen-activated protein kinase, an upstream activator of Bub1. Thus, by
      perturbing Bub1 function, our observations suggest a new mechanism whereby the
      SV40 Tag oncoprotein promotes chromosomal instability and aneuploidy in
      transgenic mouse prostate cancer models. Whereas the exact details of this
      mechanism remain unclear, our novel findings raise the possibility of exploiting
      Bub1 as a new therapeutic target in the treatment of prostate cancer, the most
      common cancer in adult men in North America.

PMID- 17189387
TI  - Effect of an epidermal growth factor receptor inhibitor in mouse models of lung
      cancer.
AB  - Gefitinib (Iressa, ZD1839) is a potent high-affinity competitive tyrosine kinase
      inhibitor aimed primarily at epidermal growth factor receptor (EGFR). Inhibitors
      in this class have recently been approved for clinical use in the treatment of
      advanced non-small cell lung cancer as monotherapy following failure of
      chemotherapy. We examined the efficacy of gefitinib on lung tumorigenesis in
      mouse models using both postinitiation and progression protocols. Gefitinib was
      given at a dose of 200 mg/kg body weight (i.g.) beginning either 2 or 12 weeks
      following carcinogen initiation. In the postinitiation protocol, gefitinib
      significantly inhibited both tumor multiplicity (approximately 70%) and tumor
      load (approximately 90%) in A/J or p53-mutant mice (P < 0.0001). Interestingly,
      gefitinib was also highly effective against lung carcinogenesis in the
      progression protocol when individual animals already have multiple preinvasive
      lesions in the lung. Gefitinib exhibited approximately 60% inhibition of tumor
      multiplicity and approximately 80% inhibition of tumor load when compared with
      control mice (both P < 0.0001). These data show that gefitinib is a potent
      chemopreventive agent in both wild-type and p53-mutant mice and that a delayed
      administration was still highly effective. Analyses of mutations in the EGFR and
      K-ras genes in lung tumors from either control or treatment groups showed no
      mutations in EGFR and consistent mutation in K-ras. Using an oligonucleotide
      array on control and gefitinib-treated lesions showed that gefitinib treatment
      failed to alter the activity or the expression level of EGFR. In contrast,
      gefitinib treatment significantly altered the expression of a series of genes
      involved in cell cycle, cell proliferation, cell transformation, angiogenesis,
      DNA synthesis, cell migration, immune responses, and apoptosis. Thus, gefitinib
      showed highly promising chemopreventive and chemotherapeutic activity in this
      mouse model of lung carcinogenesis.

PMID- 17189388
TI  - Peptide aptamers with binding specificity for the intracellular domain of the
      ErbB2 receptor interfere with AKT signaling and sensitize breast cancer cells to
      Taxol.
AB  - The ErbB2 receptor tyrosine kinase is overexpressed in approximately 30% of
      breast tumor cases and its overexpression correlates with an unfavorable
      prognosis. A major contributor for this course of the disease is the
      insensitivity of these tumors toward chemotherapy. Monoclonal antibodies,
      inhibiting the ligand-induced activation of the receptor and tyrosine kinase
      inhibitors acting on the intrinsic enzymatic activity of the intracellular
      domain, have been developed as targeted drugs. Both have been shown to be
      beneficial for breast cancer patients. We targeted a third aspect of receptor
      function: its association with intracellular signaling components. For this
      purpose, we selected peptide aptamers, which specifically interact with defined
      domains of the intracellular part of the receptor. The peptide aptamers were
      selected from a random peptide library using a yeast two-hybrid system with the
      intracellular tyrosine kinase domain of ErbB2 as a bait construct. The peptide
      aptamer AII-7 interacts with high specificity with the ErbB2 receptor in vitro
      and in vivo. The aptamers colocalized with the intracellular domain of ErbB2
      within cells. We investigated the functional consequences of the aptamer
      interaction with the ErbB2 receptor within tumor cells. The aptamer sequences
      were either expressed intracellularly or introduced into the cells as recombinant
      aptamer proteins. The phosphorylation of p42/44 mitogen-activated protein kinase
      was nearly unaffected and the activation of signal transducers and activators of
      transcription-3 was only modestly reduced. In contrast, they strongly inhibited
      the induction of AKT kinase in MCF7 breast cancer cells treated with heregulin,
      whereas AKT activation downstream of insulin-like growth factor I or epidermal
      growth factor receptor was not or only slightly affected. High AKT activity is
      responsible for the enhanced resistance of ErbB2-overexpressing cancer cells
      toward chemotherapeutic agents. Peptide aptamer interference with AKT activation
      resulted in the restoration of regular sensitivity of breast cancer cells toward
      Taxol.

PMID- 17189389
TI  - Effective strategies for tumors affecting chemopreventive metabolism.

PMID- 17189390
TI  - Circulating methylated DNA: a new generation of tumor markers.

PMID- 17189391
TI  - Chips to bedside: incorporation of microarray data into clinical practice.

PMID- 17189392
TI  - Targeting von Hippel-Lindau pathway in renal cell carcinoma.
AB  - Inheritance of a defective copy of the von Hippel-Lindau (VHL) gene leads to the
      most common cause of inherited renal cell carcinoma (RCC). In addition, most
      patients with sporadic RCC have aberrant VHL. In the absence of VHL, hypoxia
      inducible factor alpha accumulates, leading to production of several growth
      factors, including vascular endothelial growth factor and platelet-derived growth
      factor. We review here the biology of RCC and how a combination of proximal and
      distal block of VHL/hypoxia-inducible factor alpha pathway by novel targeted
      agents, including sunitinib, sorafenib, bevacizumab, everolimus, and
      temsirolimus, has led to significant improvements in progression-free survival.

PMID- 17189393
TI  - Epidermal growth factor receptor activation: how exon 19 and 21 mutations changed
      our understanding of the pathway.
AB  - The discovery of epidermal growth factor receptor (EGFR) mutations in never
      smokers has been the most relevant finding ever in non-small cell lung cancer.
      When patients whose tumors bear the sensitizing mutations are treated with the
      tyrosine kinase inhibitors gefitinib or erlotinib, we witness response rates and
      durations never before reported, including complete responses. At the same time,
      the presence of EGFR mutations has raised numerous new questions, tantalizing
      data, and new challenges for treatment. This is particularly true as we try to
      generalize the findings in lung cancer to other malignancies. The indiscriminate
      use of gefitinib or erlotinib in the general lung cancer population results in
      meager survival benefit for patients. Similarly, the tyrosine kinase inhibitors
      have limited activity in a variety of tumor types with EGFR overexpression. This
      has led to the question of whether EGFR remains a viable target in patients other
      than those whose tumors contain mutations, and whether the modest activity of
      cetuximab in colorectal cancer and head and neck cancer represents all that we
      can expect from inhibition of this pathway in the absence of mutation. Mechanisms
      of pathway activation other than mutation have been discovered in recent years,
      and include overexpression mediated by gene amplification or by amplification of
      a dinucleotide repeat in the EGFR promoter, mutation of an extracellular region
      on EGFR generating a mutant protein termed EGFRvIII, and enhanced signaling due
      to heterodimerization with other members of the EGFR family, particularly
      overexpression of HER2/HER3. The extent to which these paths to EGFR activation
      will confer sensitivity to the tyrosine kinase inhibitors or to EGFR monoclonal
      antibodies is being explored. Thus far, published clinical data suggest that
      there is little room for the administration of gefitinib or erlotinib in the
      absence of EGFR mutations. The five articles in this edition of CCR Focus will
      address the various mechanisms of EGFR pathway activation and provide insight
      into the potential for translation into clinical relevance.

PMID- 17189394
TI  - Update on epidermal growth factor receptor mutations in non-small cell lung
      cancer.
AB  - In 2004, several investigators reported that somatic mutations in the epidermal
      growth factor receptor gene were associated with clinical responses to erlotinib
      and gefitinib in patients with non-small cell lung cancer. Since then, multiple
      groups have examined the biological properties that such mutations confer as well
      as the clinical relevance of these mutations in patients with non-small cell lung
      cancer. Although a tremendous amount of knowledge has been gained in the past 2
      years, there remain a number of important epidemiologic, biological, and clinical
      questions.

PMID- 17189395
TI  - Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and
      response to gefitinib and other EGFR-targeting drugs.
AB  - The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases,
      including EGFR, HER2/erbB2, and HER3/erbB3, is an attractive target for antitumor
      strategies. Aberrant EGFR signaling is correlated with progression of various
      malignancies, and somatic tyrosine kinase domain mutations in the EGFR gene have
      been discovered in patients with non-small cell lung cancer responding to EGFR
      targeting small molecular agents, such as gefitinib and erlotinib. EGFR
      overexpression is thought to be the principal mechanism of activation in various
      malignant tumors. Moreover, an increased EGFR copy number is associated with
      improved survival in non-small cell lung cancer patients, suggesting that
      increased expression of mutant and/or wild-type EGFR molecules could be molecular
      determinants of responses to gefitinib. However, as EGFR mutations and/or gene
      gains are not observed in all patients who respond partially to treatment,
      alternative mechanisms might confer sensitivity to EGFR-targeting agents.
      Preclinical studies showed that sensitivity to EGFR tyrosine kinase inhibitors
      depends on how closely cell survival and growth signalings are coupled with EGFR,
      and also with HER2 and HER3, in each cancer. This review also describes a
      possible association between EGFR phosphorylation and drug sensitivity in cancer
      cells, as well as discussing the antiangiogenic effect of gefitinib in
      association with EGFR activation and phosphatidylinositol 3-kinase/Akt activation
      in vascular endothelial cells.

PMID- 17189396
TI  - Mechanisms of egfr gene transcription modulation: relationship to cancer risk and
      therapy response.
AB  - The epidermal growth factor receptor (EGFR) plays a crucial role in growth,
      differentiation, and motility of normal as well as cancer cells. For predictive
      cancer diagnostics and therapeutic targeting of EGFR, it is important to know how
      the expression level of EGFR is controlled and related to receptor signaling. A
      novel transcriptional regulation mechanism has been described that depends on the
      length of a CA repeat in intron 1 [CA simple sequence repeat 1 (CA SSR I)] of the
      EGFR gene. Thereby, the number of CA repeats is inversely correlated to pre-mRNA
      synthesis. Indirect evidence for the importance of this mechanism includes the
      preferential occurrence of amplifications in cancer tissue harboring short CA
      repeats in this sequence and the discovery of distinct alleles in young breast
      cancer patients with a family history of the disease and in Japanese breast
      cancer patients. It can be postulated that the length of the CA repeat influences
      DNA bendability and, in consequence, the binding of repressor proteins. In
      summary, it seems that the CA SSR I represents an inherited variable for response
      to anti-EGFR therapies that could be determined before therapy. Moreover, the
      potential for synergistic effects with other polymorphism [e.g., EGFR R497K (HER
      1 497K) and CCND1 A870G] leading to a simultaneous increase of EGFR signaling
      activity and expression should be investigated. From a practical perspective,
      assessment of the CA SSR I number of CA dinucleotide repeats as a predictor for
      clinical outcome is very attractive because it is a constant feature that does
      not change over time and can be easily measured in normal and cancer tissues
      (blood cells, skin, and tumor biopsies) in an assay that is technically simple,
      objective, and even quantitative.

PMID- 17189397
TI  - Epidermal growth factor receptor - mediated signal transduction in the
      development and therapy of gliomas.
AB  - The epidermal growth factor receptor (EGFR) and its ligands figure prominently in
      the biology of gliomas, the most common tumors of the central nervous system
      (CNS). Although their histologic classification seems to be straightforward,
      these tumors constitute a heterogeneous class of related neoplasms. They are
      associated with a variety of molecular abnormalities affecting signal
      transduction, transcription factors, apoptosis, angiogensesis, and the
      extracellular matrix. Under normal conditions, these same interacting factors
      drive CNS growth and development. We are now recognizing the diverse molecular
      genetic heterogeneity that underlies tumors classified histologically into three
      distinct grades. This recognition is leading to new therapeutic strategies
      targeted directly at specific molecular subtypes. In this article, we will review
      the role of EGFR and related molecular pathways in the genesis of the normal CNS
      and their relationship to glial tumorigenesis. We will discuss barriers to
      effective treatment as they relate to anatomic specialization of the CNS. We will
      also consider the ways in which specific EGFR alterations common to glioma
      reflect outcomes following treatment with targeted therapies, all with an eye
      towards applying this understanding to improved patient outcomes.

PMID- 17189398
TI  - Sorafenib for the treatment of advanced renal cell carcinoma.
AB  - PURPOSE: This report describes the U.S. Food and Drug Administration (FDA) review
      and approval of sorafenib (Nexavar, BAY43-9006), a new small-molecule, oral,
      multi-kinase inhibitor for the treatment of patients with advanced renal cell
      carcinoma (RCC). EXPERIMENTAL DESIGN: After meeting with sponsors during
      development studies of sorafenib, the FDA reviewed the phase 3 protocol under the
      Special Protocol Assessment mechanism. Following new drug application submission,
      FDA independently analyzed the results of two studies in advanced RCC: a large,
      randomized, double-blinded, phase 3 international trial of single-agent sorafenib
      and a supportive phase 2 study. RESULTS: In the phase 3 trial, 902 patients with
      advanced progressive RCC after one prior systemic therapy were randomized to 400
      mg sorafenib twice daily plus best supportive care or to a matching placebo plus
      best supportive care. Primary study end points included overall survival and
      progression-free survival (PFS). A PFS analysis, pre-specified and conducted
      after a total of 342 events, showed statistically significant superiority for the
      sorafenib group (median = 167 days) compared with that for the controls (median =
      84 days, log-rank P < 0.000001); the sorafenib/placebo hazard ratio was 0.44 (95%
      confidence interval, 0.35-0.55). Results were similar regardless of patient risk
      score, performance status, age, or prior therapy. The (partial) response rate to
      sorafenib was 2.1%. Overall survival results are preliminary. The principal
      toxicities in the sorafenib patients included reversible skin rashes in 40% and
      hand-foot skin reaction in 30%; diarrhea was reported in 43%, treatment-emergent
      hypertension was reported in 17%, and sensory neuropathic changes were reported
      in 13%. Grade 4 adverse events were uncommon. Grade 3 adverse events were hand
      foot skin reaction (6%), fatigue (5%), and hypertension (3%). Laboratory findings
      included asymptomatic hypophosphatemia in 45% of sorafenib patients versus 11% in
      the placebo arm and elevation of serum lipase in 41% of sorafenib patients versus
      30% in the placebo arm. Grade 4 pancreatitis was reported in two sorafenib
      patients, although both patients subsequently resumed sorafenib, with one at full
      dose. CONCLUSIONS: Sorafenib received FDA regular approval on December 20, 2005
      for the treatment of advanced RCC based on the persuasive magnitude of
      improvement in PFS with acceptable safety. The recommended dose is 400 mg (two
      200-mg tablets) twice daily taken either 1 h before or 2 h after meals. Adverse
      events were accommodated by temporary dose interruptions or reductions.

PMID- 17189399
TI  - Maspin: the new frontier.
AB  - Maspin (mammary serine protease inhibitor) was identified in 1994 by subtractive
      hybridization analysis of normal mammary tissue and breast cancer cell lines.
      Subsequently, emerging evidence portrays maspin as a multifaceted protein,
      interacting with diverse group of intercellular and extracellular proteins,
      regulating cell adhesion, motility, apoptosis, and angiogenesis and critically
      involved in mammary gland development. The tissue-specific expression of maspin
      is epigenetically controlled, and aberrant methylation of maspin promoter is
      closely associated with maspin gene silencing. Identification of new tissue sites
      expressing maspin and novel maspin-binding partners has expanded the horizon for
      maspin research and promises maspin-based therapeutic approaches for combating
      cancer. This perspective briefly outlines the past and present strides in
      deciphering this unique molecule and speculates on new frontiers in maspin
      research and prospects of maspin as a diagnostic/prognostic indicator in cancer.

PMID- 17189400
TI  - Amplification and overexpression of CACNA1E correlates with relapse in favorable
      histology Wilms' tumors.
AB  - PURPOSE: The most well established molecular markers of poor outcome in Wilms'
      tumor are loss of heterozygosity at chromosomes 1p and/or 16q, although to date
      no specific genes at these loci have been identified. We have previously shown a
      link between genomic gain of chromosome 1q and tumor relapse and sought to
      further elucidate the role of genes on 1q in treatment failure. EXPERIMENTAL
      DESIGN: Microarray-based comparative genomic hybridization identified a
      microamplification harboring a single gene (CACNA1E) at 1q25.3 in 6 of 76 (7.9%)
      Wilms' tumors, correlating with a shorter relapse-free survival (P = 0.0044, log
      rank test). Further characterization of this gene was carried out by measuring
      mRNA and protein expression as well as stable transfection of HEK293 cells.
      RESULTS: Overexpression of the CACNA1E transcript was associated with DNA copy
      number (P = 0.0204, ANOVA) and tumor relapse (P = 0.0851, log-rank test).
      Immunohistochemistry against the protein product Ca(V)2.3 revealed expression
      localized to the apical membrane in the distal tubules of normal kidney but not
      to the metanephric blastemal cells of fetal kidney from which Wilms' tumors
      arise. Nuclear localization in 99 of 160 (61.9%) Wilms' tumor cases correlated
      with a reduced relapse-free survival, particularly in cases treated with
      preoperative chemotherapy (P = 0.009, log-rank test). Expression profiling of
      stably transfected HEK293 cells revealed specific up-regulation of the immediate
      early response genes EGR1/EGR2/EGR3 and FOS/FOSB, mediated by activation of the
      MEK/ERK5/Nur77 pathway. CONCLUSIONS: These data identify a unique genetic
      aberration with direct clinical relevance in Wilms' tumor relapse and provide
      evidence for a potential novel mechanism of treatment resistance in these tumors.

PMID- 17189401
TI  - Beta2-microglobulin promotes the growth of human renal cell carcinoma through the
      activation of the protein kinase A, cyclic AMP-responsive element-binding
      protein, and vascular endothelial growth factor axis.
AB  - PURPOSE: Beta(2)-microglobulin (beta2M), a soluble protein secreted by cancer and
      host inflammatory cells, has various biological functions, including antigen
      presentation. Because aberrant expression of beta2M has been reported in human
      renal cell carcinoma, we investigated the effects of beta2M overexpression on
      cancer cell growth and analyzed its molecular signaling pathway. EXPERIMENTAL
      DESIGN: We established clonal cell lines that overexpressed beta2M in human renal
      cell carcinoma (SN12C) cells and then examined cell growth in vitro and in vivo
      and studied the beta2M-mediated downstream cell signaling pathway. RESULTS: Our
      results showed that beta2M expression positively correlates with (a) in vitro
      growth on plastic dishes and as Matrigel colonies, (b) cell invasion and
      migration in Boyden chambers, and (c) vascular endothelial growth factor (VEGF)
      expression and secretion by cells. We found, in addition, that beta2M mediates
      its action through increased phosphorylation of cyclic AMP-responsive element
      binding protein (CREB) via the protein kinase A-CREB axis, resulting in increased
      VEGF expression and secretion. In convergence with this signal axis, beta2M
      overexpression also activated both phosphatidylinositol 3-kinase/Akt and mitogen
      activated protein kinase pathways. Beta2M overexpression induced accelerated
      growth of SN12C in mouse subcutis and bone. Interrupting the beta2M signaling
      pathway using small interfering RNA led to apoptosis with increased activation of
      caspase-3 and caspase-9 and cleaved poly(ADP-ribose) polymerase. CONCLUSIONS: Our
      results showed for the first time that the beta2M-protein kinase A-CREB-VEGF
      signaling axis plays a crucial role in support of renal cell carcinoma growth and
      progression and reveals a novel therapeutic target.

PMID- 17189402
TI  - Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T cells in patients with
      malignant glioma reveals differential expression of the immunologic transcriptome
      compared with T cells from healthy volunteers.
AB  - PURPOSE: Analyses of T-cell mRNA expression profiles in glioblastoma multiforme
      has not been previously reported but may help to define and characterize the
      immunosuppressed phenotype in patients with this type of cancer. EXPERIMENTAL
      DESIGN: We did microarray studies that have shown significant and fundamental
      differences in the expression profiles of CD4(+) and CD8(+) T cells and
      immunosuppressive CD4(+)CD25(+)CD45RO(+)FoxP3(+) regulatory T cells (T(reg)) from
      normal healthy volunteers compared with patients with newly diagnosed
      glioblastoma multiforme. For these investigations, we isolated total RNA from
      enriched CD4(+) and CD8(+) T cell or T(reg) cell populations from age-matched
      individuals and did microarray analyses. RESULTS: ANOVA and principal components
      analysis show that the various T cell compartments exhibit consistently similar
      mRNA expression profiles among individuals within either healthy or brain tumor
      groups but reflect significant differences between these groups. Compared with
      healthy volunteers, CD4(+) and CD8(+) T cells from patients with glioblastoma
      multiforme display coordinate down-regulation of genes involved in T cell
      receptor ligation, activation, and intracellular signaling. In contrast, T(regs)
      from patients with glioblastoma multiforme exhibit increased levels of
      transcripts involved in inhibiting host immunity. CONCLUSION: Our findings
      support the notion that key differences between expression profiles in T-cell
      populations from patients with glioblastoma multiforme results from differential
      expression of the immunologic transcriptome, such that a limited number of genes
      are principally important in producing the dysregulated T-cell phenotype.

PMID- 17189403
TI  - The coamplification pattern of the MYCN amplicon is an invariable attribute of
      most MYCN-amplified human neuroblastomas.
AB  - PURPOSE: Fifteen percent to 20% of human neuroblastomas show amplification of the
      MYCN oncogene physiologically located at chromosome 2p24-25, indicating an
      aggressive subtype of human neuroblastoma with a poor clinical outcome. Recent
      findings revealed that the structure of the amplicon differs interindividually
      and that coamplification of genes in telomeric proximity to MYCN might play a
      relevant role in neuroblastoma development and response to treatment,
      respectively. We now asked if the amplicon structure is an invariable attribute
      of an individual tumor or if the coamplification pattern could change during
      progress or in case of recurrent disease. EXPERIMENTAL DESIGN: We used a
      previously described multiplex PCR approach to analyze the coamplification status
      of MYCN-amplified human neuroblastomas (n = 33) in tumor tissue at the time of
      initial diagnosis and in consecutive tissue specimens at later time points after
      initial treatment or from relapsing disease. The MYCN copy number per haploid
      genome (Mcn/hg) in these specimens was determined in a separate duplex PCR.
      RESULTS: In 32 of the 33 investigated tumors, the amplicon structure showed no
      changes after initial chemotherapy and in recurrent disease. Mcn/hg showed a
      decrease after initial treatment (n = 23), whereas we found a significant
      increase in recurrent disease (n = 10). CONCLUSION: Our data indicate that the
      initial determined structure of the 2p24-25 amplicon is a consistent attribute in
      the great majority of the individual MYCN-amplified neuroblastomas and shows no
      plasticity during or after chemotherapy. Observed changes in the Mcn/hg over the
      course of disease are in line with preexisting cell culture findings.

PMID- 17189404
TI  - Aberrant promoter methylation profile and association with survival in patients
      with non-small cell lung cancer.
AB  - PURPOSE: The aim of this study was to investigate the prognostic value of
      hypermethylation of tumor suppressor genes in patients with non-small cell lung
      cancer (NSCLC). EXPERIMENTAL DESIGN: We examined the methylation status of nine
      genes in 155 tumors from patients with NSCLC using quantitative methylation
      specific PCR. We analyzed the associations between gene methylation status and
      overall patient survival. RESULTS: The methylation index, defined as the ratio
      between the number of methylated genes and the number of genes tested, was
      significantly higher in adenocarcinomas (0.38 +/- 0.20) than in squamous cell
      carcinomas (0.30 +/- 0.22; P = 0.027), in tumors from older patients (0.37 +/-
      0.20) than younger patients (0.30 +/- 0.22; P = 0.040), and in tumors from
      heavier smokers (0.39 +/- 0.21) than lighter smokers (0.29 +/- 0.20; P = 0.042).
      In the Cox proportional hazards model, p16 methylation was associated with
      significantly poorer survival [hazard ratio, 1.95; 95% confidence interval (95%
      CI), 1.21-3.39]. Kaplan-Meier survival curves showed that patients with
      hypermethylated p16 had significantly shorter survival (median = 21.7 months)
      than patients without p16 hypermethylation (median = 62.5 months; P = 0.0001, log
      rank test). Hypermethylation of CDH1 or TIMP3 gene was associated with
      significantly better survival with hazard ratios of 0.51 (95% CI, 0.29-0.90) and
      0.59 (95% CI, 0.36-0.97), respectively. Joint analysis of these three genes
      showed a significant trend for poorer survival as the number of unfavorable
      events increased (P = 0.0007). CONCLUSION: Hypermethylation of multiple genes
      exhibited significant differential effect on NSCLC patient survival. Assessment
      of the effect of each methylated gene on survival is needed to provide optimal
      prognostic value.

PMID- 17189405
TI  - Vascular cell adhesion molecule 1 predicts cancer-free survival in clear cell
      renal carcinoma patients.
AB  - PURPOSE: Vascular cell adhesion molecule 1 (VCAM1) is a cell surface glycoprotein
      implicated in various pathophysiologic conditions. We measured VCAM1 expression
      levels in tumor tissues and evaluated its significance and prognostic use in
      renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: We used real-time quantitative
      PCR to examine the VCAM1 expression levels of a total of 485 sporadic renal
      tumors, including 429 clear cell, 21 papillary, 17 chromophobe, 11 oncocytomas,
      and 7 collecting duct carcinomas. We retrospectively examined the relationship of
      this expression to various clinicopathologic variables and the von Hippel-Lindau
      alteration status. We evaluated its significance with respect to patient survival
      rates using the Cox regression model combined with the split-sample method.
      RESULTS: Compared with normal kidney samples (n = 43), VCAM1 was significantly up
      regulated in clear cell RCC and papillary RCC, whereas it was down-regulated in
      chromophobe RCC and oncocytoma. In clear cell RCC, VCAM1 expression levels were
      apparently high in patients asymptomatic at presentation and in patients with
      small tumor size, low-stage, low-grade, microvascular invasion-negative, and von
      Hippel-Lindau alteration-positive tumors. Univariate analyses showed that VCAM1
      high expression is strongly associated with better outcomes in clear cell and
      papillary RCCs. Further, Cox multivariate analysis models combined with the split
      sample method revealed that this association is significant only in cancer-free
      survival for patients with clear cell RCC after curative surgical resection.
      CONCLUSIONS: VCAM1 expression levels were found to be histologically subtype
      specific in renal tumors. Determination of the VCAM1 expression level as a
      biomarker can provide useful prognostic information for patients with clear cell
      RCC.

PMID- 17189406
TI  - Methylation of serum DNA is an independent prognostic marker in colorectal
      cancer.
AB  - PURPOSE: Aberrant CpG island hypermethylation is a feature of a subgroup of
      colorectal cancers, which can be detected in the serum of affected patients. This
      study was designed to identify methylation targets with prognostic significance
      in the serum of patients with colorectal cancer. EXPERIMENTAL DESIGN: In a gene
      evaluation set consisting of sera from 24 patients with local colorectal cancers,
      14 with metastasized disease, and 20 healthy controls, the genes HPP1/TPEF, HLTF,
      and hMLH1 were identified as potential serum DNA methylation markers. These genes
      were further analyzed in a test set of sera of 104 patients with colorectal
      cancer. RESULTS: Methylation of HLTF, HPP1/TPEF, and hMLH1 was found to be
      significantly correlated with tumor size, and methylation of HLTF and HPP1/TPEF
      was significantly associated with metastatic disease and tumor stage. Moreover,
      methylation of HPP1/TPEF was also associated with serum carcinoembryonic antigen.
      The prognostic relevance of methylation of these genes was tested in
      pretherapeutic sera of 77 patients with known follow-up. Patients with
      methylation of HPP1/TPEF or HLTF were found to have unfavorable prognosis (P =
      0.001 and 0.008). In contrast, serum methylation of hMLH1 was not associated with
      a higher risk of death. Multivariate analysis showed methylated HPP1 and/or HLTF
      serum DNA to be independently associated with poor outcome and a relative risk of
      death of 3.4 (95% confidence interval, 1.4-8.1; P = 0.007). CONCLUSIONS: These
      data show that the methylation status of specific genes in the serum of patients
      with colorectal cancer has the potential to become a pretherapeutic predictor of
      outcome.

PMID- 17189407
TI  - Implications of methylation patterns of cancer genes in salivary gland tumors.
AB  - PURPOSE: We investigated the methylation status and protein expression of four
      tumor suppressor genes to determine their role in salivary gland tumorigenesis.
      EXPERIMENTAL DESIGN: We performed methylation-specific PCR and protein analyses
      of 29 normal salivary glands, 23 benign, and 79 malignant salivary gland
      neoplasms to determine the pattern and potential diagnostic and/or biological
      role of the RASSF1, RARbeta2, DAPK, and MGMT tumor suppressor gene methylation in
      these tumors. RESULTS: No methylation was detected in the normal tissues.
      Methylation occurred in 9 of 23 (39.1%) benign tumors; 3 (25.0%) pleomorphic
      adenomas and 6 (66.7%) Warthin's tumors at the MGMT, DAPK, or RASSF1 genes.
      Methylation occurred in 33 of 79 (41.8%) malignant tumors; 8 (30.8%) adenoid
      cystic carcinomas, 6 (33.3%) mucoepidermoid carcinomas, 6 (42.9%) acinic cell
      carcinomas, and 13 (62.0%) salivary duct carcinomas. RASSF1 and RARbeta2
      represented 75.8% of methylation events occurring most frequently in salivary
      duct and acinic cell carcinomas. Overall, we found no significant correlation
      between protein expression and methylation status of individual genes, but
      observed low or absent protein expression in several methylated tumors.
      Significant correlations were found between methylation and aggressive malignant
      phenotypes (P = 0.0004) and age (P = 0.05). CONCLUSIONS: (a) Benign and malignant
      salivary tumors differed in the frequency and pattern of gene methylation; (b)
      high-grade carcinomas were significantly methylated compared with low-grade
      phenotypes; (c) RASSF1 and RARbeta2 were highly methylated in malignant tumors
      and can be targeted for therapy; and (d) methylation pattern may serve as a
      diagnostic and biological marker in assessing these tumors.

PMID- 17189408
TI  - Molecular profiling of ADAM12 in human bladder cancer.
AB  - PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to
      be an interesting biomarker for breast cancer. The purpose of this study was to
      determine the gene and protein expression profiles of ADAM12 in different grades
      and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12 gene expression was
      evaluated in tumors from 96 patients with bladder cancer using a customized
      Affymetrix GeneChip. Gene expression in bladder cancer was validated using
      reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein
      expression was evaluated by immunohistochemical staining on tissue arrays of
      bladder cancers. The presence and relative amount of ADAM12 in the urine of
      cancer patients were determined by Western blotting and densitometric
      measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up
      regulated in bladder cancer, as determined by microarray analysis, and the level
      of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR,
      quantitative PCR, and in situ hybridization validated the gene expression
      results. Using immunohistochemistry, we found ADAM12 protein expression
      correlated with tumor stage and grade. Finally, ADAM12 could be detected in the
      urine by Western blotting; ADAM12 was present in higher levels in the urine from
      patients with bladder cancer compared with urine from healthy individuals.
      Significantly, following removal of tumor by surgery, in most bladder cancer
      cases examined, the level of ADAM12 in the urine decreased and, upon recurrence
      of tumor, increased. CONCLUSIONS: ADAM12 is a promising biomarker of bladder
      cancer.

PMID- 17189409
TI  - Ki-67 is an independent predictor of bladder cancer outcome in patients treated
      with radical cystectomy for organ-confined disease.
AB  - PURPOSE: To determine the association of the cell proliferative marker Ki-67 with
      pathologic features and disease prognosis in patients with transitional cell
      carcinoma (TCC) of the urinary bladder. METHODS: Immunohistochemical staining for
      Ki-67 was done on serial cuts from tissue microarrays containing cystectomy
      specimens from 9 patients without bladder cancer and 226 consecutive patients
      with bladder TCC. We also assessed malignant lymph nodes from 50 of the 226
      cystectomy patients. RESULTS: Ki-67 expression was increased in 42.5% cystectomy
      specimens and in 54% metastatic lymph nodes. In contrast, it was absent in all
      nine benign cystectomy specimens. Ki-67 overexpression was associated with
      advanced pathologic stage, higher grade, lymphovascular invasion, and metastases
      to lymph nodes (P = 0.001, 0.040, 0.031, and 0.036, respectively). In
      multivariate analyses, pathologic stage and lymph node metastases were
      independent predictors of disease recurrence and bladder cancer-specific
      mortality. In the subgroup of patients with organ-confined disease (<pT(3) N(0);
      n = 91), excluding patients who received neoadjuvant or adjuvant chemotherapy, Ki
      67 status was an independent predictor of both disease recurrence (risk ratio,
      7.591; P = 0.001) and bladder cancer-specific mortality (risk ratio, 4.045; P =
      0.041). CONCLUSIONS: Ki-67 overexpression is associated with features of
      aggressive bladder TCC and adds independent prognostic information to standard
      pathologic features for prediction of clinical outcome after radical cystectomy.

PMID- 17189410
TI  - Contribution of ABL kinase domain mutations to imatinib resistance in different
      subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic
      Myeloid Leukemia.
AB  - PURPOSE: ABL kinase domain mutations have been implicated in the resistance to
      the BCR-ABL inhibitor imatinib mesylate of Philadelphia-positive (Ph+) leukemia
      patients. EXPERIMENTAL DESIGN: Using denaturing high-performance liquid
      chromatography and sequencing, we screened for ABL kinase domain mutations in 370
      Ph+ patients with evidence of hematologic or cytogenetic resistance to imatinib.
      RESULTS: Mutations were found in 127 of 297 (43%) evaluable patients. Mutations
      were found in 27% of chronic-phase patients (14% treated with imatinib frontline;
      31% treated with imatinib post-IFN failure), 52% of accelerated-phase patients,
      75% of myeloid blast crisis patients, and 83% of lymphoid blast crisis/Ph+ acute
      lymphoblastic leukemia (ALL) patients. Mutations were associated in 30% of
      patients with primary resistance (44% hematologic and 28% cytogenetic) and in 57%
      of patients with acquired resistance (23% patients who lost cytogenetic response;
      55% patients who lost hematologic response; and 87% patients who progressed to
      accelerated phase/blast crisis). P-loop and T315I mutations were particularly
      frequent in advanced-phase chronic myeloid leukemia and Ph+ ALL patients, and
      often accompanied progression from chronic phase to accelerated phase/blast
      crisis. CONCLUSIONS: We conclude that (a) amino acid substitutions at seven
      residues (M244V, G250E, Y253F/H, E255K/V, T315I, M351T, and F359V) account for
      85% of all resistance-associated mutations; (b) the search for mutations is
      important both in case of imatinib failure and in case of loss of response at the
      hematologic or cytogenetic level; (c) advanced-phase chronic myeloid leukemia and
      Ph+ ALL patients have a higher likelihood of developing imatinib-resistant
      mutations; and (d) the presence of either P-loop or T315I mutations in imatinib
      treated patients should warn the clinician to reconsider the therapeutic
      strategy.

PMID- 17189411
TI  - Immunologic and clinical effects of injecting mature peptide-loaded dendritic
      cells by intralymphatic and intranodal routes in metastatic melanoma patients.
AB  - PURPOSE: A phase I/II trial was conducted to evaluate clinical and immunologic
      responses after intralymphatic and intranodal injections of mature dendritic
      cells. EXPERIMENTAL DESIGN: Fourteen patients with a metastatic melanoma received
      matured dendritic cells, loaded with Melan-A/MART-1 and/or NA17-A peptides and
      keyhole limpet hemocyanin. The cells were matured overnight with Ribomunyl, a
      toll-like receptor ligand, and IFN-gamma, which ensured the production of high
      levels of interleukin-12p70. Dendritic cells were injected at monthly intervals,
      first into an afferent lymphatic and then twice intranodally. Immunologic
      responses were monitored by tetramer staining of circulating CD8(+) lymphocytes
      and delayed-type hypersensitivity tests. RESULTS: Dendritic cell vaccination
      induced delayed-type hypersensitivity reactivity toward NA17-A-pulsed, keyhole
      limpet hemocyanin-pulsed, and Melan-A-pulsed dendritic cells in 6 of 10, 4 of 11,
      and 3 of 9 patients, respectively. Four of the 12 patients analyzed by tetramer
      staining showed a significantly increased frequency of Melan-A-specific T cells,
      including one patient vaccinated only with NA17-A-pulsed dendritic cells.
      Furthermore, 2 of the 12 analyzed patients had a significant increase of NA17-A
      specific T cells, including one immunized after an optional additional treatment
      course. No objective clinical response was observed. Two patients were stabilized
      at 4 and 10 months and three patients are still alive at 30, 39, and 48 months.
      CONCLUSIONS: Injections into the lymphatic system of mature peptide-loaded
      dendritic cells with potential TH1 polarization capacities did not result in
      marked clinical results, despite immunologic responses in some patients. This
      highlights the need to improve our understanding of dendritic cell physiology.

PMID- 17189412
TI  - HER2-specific T-cell immune responses in patients vaccinated with truncated HER2
      protein complexed with nanogels of cholesteryl pullulan.
AB  - PURPOSE: We developed a complex of tumor antigen protein with a novel
      nanoparticle antigen delivery system of cholesteryl pullulan (CHP). To target
      HER2 antigen, we prepared truncated HER2 protein 1-146 (146HER2) complexed with
      CHP, the CHP-HER2 vaccine. We designed a clinical study to assess the safety of
      the vaccine and HER2-specific T-cell immune responses measured by the newly
      developed enzyme-linked immunospot assay with mRNA-transduced phytohemagglutinin
      stimulated CD4(+) T cells in HLA-A2402-positive patients with therapy-refractory
      HER2-expressing cancers. EXPERIMENTAL DESIGN: Nine patients with various types of
      solid tumors were enrolled. Each patient was s.c. vaccinated biweekly with 300
      microg of CHP-HER2 vaccine for three times followed by booster doses. HER2
      specific T-cell responses were evaluated by enzyme-linked immunospot assay by
      targeting autologous phytohemagglutinin-stimulated CD4(+) T cells transduced with
      146HER2-encoding mRNA to cover both identified peptides and unknown epitopes for
      MHC class I and class II that might exist in the sequence of the vaccine protein.
      RESULTS: CHP-HER2 vaccine was well tolerated; the only adverse effect was grade 1
      transient skin reaction at the sites of vaccination. HER2-specific CD8(+) and/or
      CD4(+) T-cell immune responses were detected in five patients who received four
      to eight vaccinations, among whom both T-cell responses were detected in these
      patients. In four patients with CD8(+) T-cell responses, two patients reacted to
      previously identified HER2(63-71) peptide and the other two reacted only to
      146HER2 mRNA-transduced cells. CONCLUSIONS: CHP-HER2 vaccine was safe and induced
      HER2-specific CD8(+) and/or CD4(+) T-cell immune responses.

PMID- 17189413
TI  - Phase I, pharmacokinetic, and biological study of erlotinib in combination with
      paclitaxel and carboplatin in patients with advanced solid tumors.
AB  - PURPOSE: To assess the feasibility of administering erlotinib, an inhibitor of
      epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with
      paclitaxel and carboplatin, and to identify pharmacokinetic interactions,
      evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek
      preliminary evidence for clinical activity. EXPERIMENTAL DESIGN: Patients with
      advanced solid malignancies were treated continuously with erlotinib at doses of
      100, 125, and 150 mg/d orally along with fixed i.v. doses of paclitaxel 225
      mg/m(2) and carboplatin AUC 6 mg x min/mL, both on day 1 every 3 weeks. RESULTS:
      Twenty evaluable patients were treated with 136 courses of erlotinib, paclitaxel,
      and carboplatin. Myelosuppression, skin rash, and diarrhea were the principal
      toxicities. Dose limiting diarrhea occurred in 1 of 6 patients at the 100 mg
      erlotinib dose level, whereas 0 of 9 evaluable patients at the 125 mg erlotinib
      dose level experienced dose limiting toxicity and 3 of 5 evaluable patients at
      150 mg erlotinib experienced dose limiting skin rash and neutropenic sepsis.
      There was no evidence of pharmacokinetic interactions between paclitaxel and
      erlotinib; however, total carboplatin exposure trended higher in the presence of
      erlotinib. No consistent downstream effects on EGFR inhibition were found in
      skin. Durable objective responses were observed in non-small-cell lung and head
      and neck cancers. CONCLUSIONS: A dose level of erlotinib 125 mg combined with
      paclitaxel 225 mg/m(2) and carboplatin AUC 6 mg.min/mL is recommended for disease
      directed studies. This phase I trial was followed by a randomized phase III study
      in non-small-cell lung cancer using a similar regimen.

PMID- 17189414
TI  - Rapid androgen cycling as treatment for patients with prostate cancer.
AB  - PURPOSE: To investigate the safety and feasibility of rapid androgen cycling for
      men with progressive prostate cancer. EXPERIMENTAL DESIGN: Schedule 1 included a
      4-week induction of androgen depletion, followed by 4-week treatment cycles of a
      monthly gonadotropin-releasing hormone agonist, testosterone on days 1 to 7, and
      an estrogen patch on days 8 to 21. Schedule 2 included a 12-week induction of
      androgen depletion followed by 4-week cycles of gonadotropin-releasing hormone
      agonist and testosterone, but no estrogens for patients with a prostate-specific
      antigen (PSA) nadir <1 ng/mL after induction. The primary end point was serially
      declining PSA trough values over six treatment cycles. RESULTS: Thirty-six
      patients were treated; 27 were evaluable after cycling, of whom 8 of 12 (67%) and
      9 of 15 (60%) on schedules 1 and 2, respectively, reached the end point. Five
      patients with PSA >1 ng/mL following induction did not cycle. No patient
      progressed radiographically or clinically during cycling. Three posttherapy PSA
      patterns were observed: a decline followed by a rapid increase in trough levels,
      a sustained decline with a plateau at a detectable nadir, and a decline to an
      undetectable nadir. Mean testosterone levels were castrate at the time of trough
      and in the normal physiologic range following androgen repletion. Major
      toxicities included grades 1 and 2 fatigue, hepatitis, gynecomastia, and hot
      flashes. CONCLUSIONS: Rapid hormonal cycling is feasible and well tolerated, and
      successive declines in PSA troughs are achievable. Although the sample size was
      small, the proportion of patients achieving declining PSA at the end of six
      cycles was comparable with that reached with continuous androgen depletion
      therapy.

PMID- 17189416
TI  - Inhibitory effects of castration in an orthotopic model of androgen-independent
      prostate cancer can be mimicked and enhanced by angiogenesis inhibition.
AB  - PURPOSE: Today, the most important treatment of advanced prostate cancer is
      castration; unfortunately, however, the long-term effect of this therapy is
      insufficient. Recent studies suggest that castration-induced prostate involution
      could be caused by primary effects in the prostate vasculature; therefore, we
      examined if antivascular treatments could mimic the effects of castration.
      EXPERIMENTAL DESIGN: Androgen-independent AT-1 prostate cancer cells were grown
      inside the ventral prostate in adult rats. Tumor-bearing animals were treated
      with an inhibitor of vascular endothelial growth factor receptor 2 and epidermal
      growth factor receptor signaling, N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1
      methylpiperidin-4-yl)methoxy]quinazolin-4-amine (ZD6474, AstraZeneca, Sodertalje,
      Sweden), and short-term effects (after 3 days) were compared with those induced
      by castration. RESULTS: Castration caused decreased vascular density in the
      normal tissue surrounding the tumor and consequently increased tumor hypoxia and
      apoptosis, and moderately decreased tumor growth. ZD6474 treatment resulted in
      decreased tumor vascular density accompanied by increased tumor hypoxia,
      apoptosis, and decreased tumor growth, suggesting that castration and
      antiangiogenic therapy work through similar mechanisms. Interestingly, castration
      or ZD6474 alone worked by reducing vascular density in the surrounding normal
      tissue and ZD6474 also in the tumor. Combined treatment with castration + ZD6474
      was more effective than castration and ZD6474 alone in inducing tumor hypoxia,
      apoptosis, necrosis, and decreasing tumor vascular density. CONCLUSION: These
      findings show that a drug that targets the vasculature in the tumor and in the
      surrounding ventral prostate lobe could mimic and even enhance the effects of
      castration. Our present findings thus suggest that castration + ZD6474 could be a
      particularly effective way to treat prostate tumors.

PMID- 17189415
TI  - Active antiviral T-lymphocyte response can be redirected against tumor cells by
      antitumor antibody x MHC/viral peptide conjugates.
AB  - PURPOSE: To redirect an ongoing antiviral T-cell response against tumor cells in
      vivo, we evaluated conjugates consisting of antitumor antibody fragments coupled
      to class I MHC molecules loaded with immunodominant viral peptides. EXPERIMENTAL
      DESIGN: First, lymphochoriomeningitis virus (LCMV)-infected C57BL/6 mice were
      s.c. grafted on the right flank with carcinoembryonic antigen (CEA)-transfected
      MC38 colon carcinoma cells precoated with anti-CEA x H-2D(b)/GP33 LCMV peptide
      conjugate and on the left flank with the same cells precoated with control anti
      CEA F(ab')(2) fragments. Second, influenza virus-infected mice were injected
      i.v., to induce lung metastases, with HER2-transfected B16F10 cells, coated with
      either anti-HER2 x H-2D(b)/NP366 influenza peptide conjugates, or anti-HER2
      F(ab')(2) fragments alone, or intact anti-HER2 monoclonal antibody. Third,
      systemic injections of anti-CEA x H-2D(b) conjugates with covalently cross-linked
      GP33 peptides were tested for the growth inhibition of MC38-CEA(+) cells, s.c.
      grafted in LCMV-infected mice. RESULTS: In the LCMV-infected mice, five of the
      six grafts with conjugate-precoated MC38-CEA(+) cells did not develop into
      tumors, whereas all grafts with F(ab')(2)-precoated MC38-CEA(+) cells did so (P =
      0.0022). In influenza virus-infected mice, the group injected with cells
      precoated with specific conjugate had seven times less lung metastases than
      control groups (P = 0.0022 and P = 0.013). Most importantly, systemic injection
      in LCMV-infected mice of anti-CEA x H-2D(b)/cross-linked GP33 conjugates
      completely abolished tumor growth in four of five mice, whereas the same tumor
      grew in all five control mice (P = 0.016). CONCLUSION: The results show that a
      physiologic T-cell antiviral response in immunocompetent mice can be redirected
      against tumor cells by the use of antitumor antibody x MHC/viral peptide
      conjugates.

PMID- 17189418
TI  - Preclinical evaluation of antiangiogenic thrombospondin-1 peptide mimetics, ABT
      526 and ABT-510, in companion dogs with naturally occurring cancers.
AB  - PURPOSE: The angiogenic phenotype of malignant cancers has been established as a
      target for cancer therapy. ABT-526 and ABT-510, two peptide mimetics of
      thrombospondin-1 (TSP-1), block angiogenesis in vitro and in vivo and slow tumor
      growth in mice. To guide the clinical development of these drugs, translational
      studies in dogs with naturally occurring cancers were initiated. EXPERIMENTAL
      DESIGN: A prospective open-label trial using ABT-510 or ABT-526 in pet dogs with
      measurable malignant spontaneously arising tumors. Endpoints included safety,
      pharmacokinetics, antitumor activity, and preliminary assessment of changes in
      circulating endothelial cell populations. RESULTS: Two-hundred and forty-two dogs
      were sequentially entered to this open-label trial. The elimination half-life for
      ABT-510 and ABT-526 was 0.7 and 0.8 h, respectively (range, 0.5-1 h). No dose
      limiting toxicities were seen in any dogs (N = 242). Forty-two dogs receiving
      peptide had objective responses (>50% reduction in tumor size; n = 6) or
      significant disease stabilization. Most objective responses were seen after 60
      days of exposure to the TSP-1 peptide. Antitumor activity was similar for both
      peptides and was seen in several histologies, including mammary carcinoma, head
      and neck carcinoma, soft tissue sarcoma, cutaneous T-cell lymphoma, and non
      Hodgkin's lymphoma. Assessment of circulating endothelial cell populations in a
      small subset of dogs suggested that effective exposure to TSP-1 peptides may be
      associated with reductions in circulating endothelial cells. CONCLUSIONS: These
      results support the safety and activity of ABT-526 and ABT-510 in dogs with
      naturally occurring malignant cancers. Data from this preclinical trial support
      the development of TSP-1 mimetic peptides as anticancer agents.

PMID- 17189417
TI  - Systemic anthrax lethal toxin therapy produces regressions of subcutaneous human
      melanoma tumors in athymic nude mice.
AB  - PURPOSE: Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal
      factor, catalytically cleaves mitogen-activated protein kinase (MAPK) kinases and
      inhibits the MAPK signaling pathways. The majority of metastatic melanomas
      possess the V599E BRAF mutation, which constitutively activates MAPK1/2
      signaling. LeTx is cytotoxic to BRAF mutant melanoma cell lines in vitro, whereas
      most normal cells are resistant to this toxin. In this study, we determine the in
      vivo potency and safety of systemically administered LeTx. EXPERIMENTAL DESIGN: A
      s.c. xenograft melanoma model in athymic nude mice was treated with different
      i.p. doses of LeTx. RESULTS: In this study, we show that in vivo systemic LeTx
      treatment of s.c. xenograft melanoma tumors in athymic nude mice yields partial
      and complete tumor regressions with minor toxicity to mice. When animal toxicity
      was observed, we did not find any histologic evidence of tissue damage.
      CONCLUSIONS: LeTx is one of the rare targeted agents to produce complete
      remissions of human melanomas in an animal model and thus warrants further
      preclinical development.

PMID- 17189419
TI  - Cooperative activity of cytotoxic chemotherapy with antiangiogenic thrombospondin
      I peptides, ABT-526 in pet dogs with relapsed lymphoma.
AB  - PURPOSE: Thrombospondin-I (TSP-I) is a natural antiangiogenic protein that
      enhances apoptosis of activated endothelial cells. A modified nonapeptide from
      TSP-I, ABT-526, has been found to be active in mouse cancer models and in dogs
      with naturally occurring cancers. To further assist in the development of ABT
      526, we report herein on its evaluation in combination with cytotoxic
      chemotherapy in pet dogs with relapsed non-Hodgkin's lymphoma (NHL). EXPERIMENTAL
      DESIGN: Ninety-four pet dogs with naturally occurring first-relapse NHL were
      entered into a prospective randomized placebo controlled double-blinded trial of
      ABT-526 plus CeeNu (Bristol-Myers Squibb, New York, NY) versus CeeNu alone.
      Endpoints included response rate, duration of response, time to progression, and
      incidence of toxicoses. RESULTS: No significant ABT-526-specific toxicities were
      seen. CeeNu-associated toxicities, including neutropenia, thrombocytopenia,
      gastroenteritis, and elevated alanine transaminase, were similar. No significant
      difference in objective response rate was seen (ABT-526 + CeeNu versus placebo +
      CeeNu, 23/49 versus 23/37; P > 0.25). Cooperative activity between ABT-526 and
      CeeNu chemotherapy was evident based on a significant increase in the median
      response duration of dogs receiving ABT-526 plus CeeNu compared with placebo plus
      CeeNu (35 versus 15 days; P < 0.05). The time to progression for responding cases
      was also significantly greater in dogs receiving ABT-526 plus CeeNu compared with
      placebo plus CeeNu (41 versus 21 days; P < 0.05). CONCLUSIONS: Results of this
      preclinical trial suggest that the activity of ABT-526 is sustained when combined
      with cytotoxic chemotherapy; furthermore, the activity seems to be associated
      with the maintenance of CeeNu-induced treatment responses. Further studies of TSP
      I peptide antiangiogenic therapy in pet dogs and humans with NHL are warranted.

PMID- 17189420
TI  - Enhancement of immunologic tumor regression by intratumoral administration of
      dendritic cells in combination with cryoablative tumor pretreatment and Bacillus
      Calmette-Guerin cell wall skeleton stimulation.
AB  - PURPOSE: We developed an effective immunotherapy, which could induce antitumor
      immune responses against shared and unique tumor antigens expressed in autologous
      tumors. EXPERIMENTAL DESIGN: Intratumoral administration of dendritic cells is
      one of the individualized immunotherapies; however, the antitumor activity is
      relatively weak. In this study, we attempted to enhance the antitumor efficacy of
      the i.t. dendritic cell administration by combining dendritic cells stimulated
      with Bacillus Calmette-Guerin cell wall skeleton (BCG-CWS) additionally with
      cryoablative pretreatment of tumors and analyzed the therapeutic mechanisms.
      RESULTS: These two modifications (cryoablation of tumors and BCG-CWS stimulation
      of dendritic cells) significantly increases the antitumor effect on both the
      treated tumor and the untreated tumor, which was distant at the opposite side, in
      a bilateral s.c. murine CT26 colon cancer model. Further analysis of the
      augmented antitumor effects revealed that the cryoablative pretreatment enhances
      the uptake of tumor antigens by the introduced dendritic cells, resulting in the
      induction of tumor-specific CD8(+) T cells responsible for the in vivo tumor
      regression of both treated and remote untreated tumors. This novel combination
      i.t. dendritic cell immunotherapy was effective against well-established large
      tumors. The antitumor efficacy was further enhanced by depletion of
      CD4(+)CD25(+)FoxP3(+) regulatory T cells. CONCLUSIONS: This novel dendritic cell
      immunotherapy with i.t. administration of BCG-CWS-treated dendritic cells
      following tumor cryoablation could be used for the therapy of cancer patients
      with multiple metastases.

PMID- 17189421
TI  - Identification of a highly immunogenic HLA-A*01-binding T cell epitope of WT1.
AB  - PURPOSE: The transcription factor Wilms tumor protein 1 (WT1) belongs to a new
      generation of tumor antigens, as it is essential for tumor cell proliferation and
      is highly expressed in various hematologic and solid malignancies. The aim of
      this study was to apply a modified reverse immunology strategy to identify
      immunogenic epitopes of WT1 which could be useful for immunotherapy. EXPERIMENTAL
      DESIGN: Potential HLA-A*01 epitopes predicted by a MHC binding algorithm were
      screened for recognition by peripheral blood mononuclear cells (PBMC) from
      patients with spontaneous T cell responses using intracellular cytokine
      cytometry. Epitope processing was shown by proteasomal cleavage. Epitope-specific
      T cells were generated from CD4+CD25+ regulatory T cell-depleted PBMC. RESULTS:
      One of five predicted HLA-A*01-binding candidate epitopes showed high
      immunogenicity as 5 of 14 patients with hematologic malignancies had WT1.317-327
      reactive T cells ranging from 0.4% to 1.5% of CD3+CD8+ T cells. Proteasomal
      degradation assays indicated the cleavage of WT1.317-327. The depletion of
      regulatory T cells from PBMCs enabled the rapid expansion of WT1.317-327-specific
      CTL, whereas no CTL could be generated from unfractionated PBMC. WT1.317-327
      specific CTL efficiently lysed an autologous WT1-expressing tumor cell line but
      not HLA-A*01-negative WT1-expressing tumor cells. Immunogenicity of the epitope
      across histologies was verified by the demonstration of spontaneous ex vivo
      WT1.317-327-specific T cell responses in two of six patients with HLA-A*01
      positive melanoma or lung cancer. CONCLUSION: In this study, a modified reverse
      immunology strategy was employed to identify a first immunogenic HLA-A*01
      restricted T cell epitope of the tumor antigen WT1, which is of considerable
      interest for use in vaccination trials.

PMID- 17189422
TI  - Transcriptional repression of hepatic cytochrome P450 3A4 gene in the presence of
      cancer.
AB  - PURPOSE: Many chemotherapeutic drugs have an inherent lack of safety due to
      interindividual variability of hepatic cytochrome P450 (CYP) 3A4 drug metabolism.
      This reduction in CYP3A4 in cancer patients is possibly mediated by cytokines
      associated with tumor-derived inflammation. We sought to examine this link by
      using an explant sarcoma in a novel transgenic mouse model of human CYP3A4
      regulation. EXPERIMENTAL DESIGN: Engelbreth-Holm-Swarm sarcoma cells were
      injected into the hindlimb of transgenic CYP3A4/lacZ mice. Hepatic expression of
      the human CYP3A4 transgene was analyzed by direct measurement of the reporter
      gene product, beta-galactosidase enzyme activity. Hepatic expression of murine
      Cyp3a was analyzed at the mRNA, protein, and function levels. The acute phase
      response was assessed by examining cytokines [interleukin-6 (IL-6) and tumor
      necrosis factor] in serum, liver, or tumor as well as hepatic expression of serum
      amyloid protein P. RESULTS: Engelbreth-Holm-Swarm sarcoma elicited an acute phase
      response that coincided with down-regulation of the human CYP3A4 transgene in the
      liver as well as the mouse orthologue Cyp3a11. The reduction of murine hepatic
      Cyp3a gene expression in tumor-bearing mice resulted in decreased Cyp3a protein
      expression and consequently a significant reduction in Cyp3a-mediated metabolism
      of midazolam. Circulating IL-6 was elevated and IL-6 protein was only detected in
      tumor tissue but not in hepatic tissue. CONCLUSIONS: The current study provides a
      mechanistic link between cancer-associated inflammation and impaired drug
      metabolism in vivo. Targeted therapy to reduce inflammation may provide improved
      clinical benefit for chemotherapy drugs metabolized by hepatic CYP3A4 by
      improving their pharmacokinetic profile.

PMID- 17189424
TI  - Microinversions in mammalian evolution.
AB  - We propose an approach for identifying microinversions across different species
      and show that microinversions provide a source of low-homoplasy evolutionary
      characters. These characters may be used as "certificates" to verify different
      branches in a phylogenetic tree, turning the challenging problem of phylogeny
      reconstruction into a relatively simple algorithmic problem. We estimate that
      there exist hundreds of thousands of microinversions in genomes of mammals from
      comparative sequencing projects, an untapped source of new phylogenetic
      characters.

PMID- 17189423
TI  - Mouse oocytes within germ cell cysts and primordial follicles contain a Balbiani
      body.
AB  - The Balbiani body or mitochondrial cloud is a large distinctive organelle
      aggregate found in developing oocytes of many species, but its presence in the
      mouse has been controversial. Using confocal and electron microscopy, we report
      that a Balbiani body does arise in mouse neonatal germline cysts and oocytes of
      primordial follicles but disperses as follicles begin to grow. The mouse Balbiani
      body contains a core of Golgi elements surrounded by mitochondria and associated
      endoplasmic reticulum. Because of their stage specificity and perinuclear rather
      than spherical distribution, these clustered Balbiani body mitochondria may have
      been missed previously. The Balbiani body also contains Trailer hitch, a widely
      conserved member of a protein complex that associates with endoplasmic
      reticulum/Golgi-like vesicles and transports specific RNAs during Drosophila
      oogenesis. Our results provide evidence that mouse oocytes develop using
      molecular and developmental mechanisms widely conserved throughout the animal
      kingdom.

PMID- 17189425
TI  - Two G-rich regulatory elements located adjacent to and 440 nucleotides downstream
      of the core poly(A) site of the intronless melanocortin receptor 1 gene are
      critical for efficient 3' end processing.
AB  - Cleavage and polyadenylation is an essential processing reaction required for the
      maturation of pre-mRNAs into stable, export- and translation-competent mature
      mRNA molecules. This reaction requires the assembly of a multimeric protein
      complex onto a bipartite core sequence element consisting of an AAUAAA hexamer
      and a GU/U-rich downstream sequence element. In this study we have analyzed 3'
      end processing of the human melanocortin 1 receptor gene (MC1R). The MC1R gene is
      an intron-free transcription unit, and its poly(A) site lacks a defined U/GU-rich
      element. We describe two G-rich sequence elements that are critical for efficient
      cleavage at the MC1R poly(A) site. The first element is located 30 nucleotides
      downstream of the cleavage site and acts as an essential closely positioned
      enhancer. The second G-rich region is positioned more than 440 nucleotides
      downstream of the MC1R processing site and is instrumental for optimal processing
      efficiency. Both G-rich sequences contain clusters of heterogeneous nuclear
      ribonucleoprotein binding motifs and act together to enhance cleavage at the MC1R
      poly(A) site.

PMID- 17189426
TI  - Intragenic suppressor mutations restore GTPase and translation functions of a
      eukaryotic initiation factor 5B switch II mutant.
AB  - Structural studies of GTP-binding proteins identified the Switch I and Switch II
      elements as contacting the gamma-phosphate of GTP and undergoing marked
      conformational changes upon GTP versus GDP binding. Movement of a universally
      conserved Gly at the N terminus of Switch II is thought to trigger the structural
      rearrangement of this element. Consistently, we found that mutation of this Gly
      in the Switch II element of the eukaryotic translation initiation factor 5B
      (eIF5B) from Saccharomyces cerevisiae impaired cell growth and the guanine
      nucleotide-binding, GTPase, and ribosomal subunit joining activities of eIF5B. In
      a screen for mutations that bypassed the critical requirement for this Switch II
      Gly in eIF5B, intragenic suppressors were identified in the Switch I element and
      at a residue in domain II of eIF5B that interacts with Switch II. The intragenic
      suppressors restored yeast cell growth and eIF5B nucleotide-binding, GTP
      hydrolysis, and subunit joining activities. We propose that the Switch II
      mutation distorts the geometry of the GTP-binding active site, impairing
      nucleotide binding and the eIF5B domain movements associated with GTP binding.
      Accordingly, the Switch I and domain II suppressor mutations induce Switch II to
      adopt a conformation favorable for nucleotide binding and hydrolysis and thereby
      reestablish coupling between GTP binding and eIF5B domain movements.

PMID- 17189427
TI  - Essential role of insulin and insulin-like growth factor 1 receptor signaling in
      cardiac development and function.
AB  - Cardiovascular disease is the leading cause of death in people with type 2
      diabetes and is linked to insulin resistance even in the absence of diabetes.
      Here we show that mice with combined deficiency of the insulin receptor and
      insulin-like growth factor 1 (IGF-1) receptor in cardiac and skeletal muscle
      develop early-onset dilated cardiomyopathy and die from heart failure within the
      first month of life despite having a normal glucose homeostasis. Mice lacking the
      insulin receptor show impaired cardiac performance at 6 months, and mice lacking
      the insulin receptor plus one Igf1r allele have slightly increased mortality. By
      contrast, mice lacking the IGF-1 receptor or the IGF-1 receptor plus one Ir
      allele appear normal. Morphological characterization and oligonucleotide array
      analysis of gene expression demonstrate that prior to development of these
      physiological defects, mice with combined deficiency of both insulin and IGF-1
      receptors have a coordinated down-regulation of genes encoding components of the
      electron transport chain and mitochondrial fatty acid beta-oxidation pathways and
      altered expression of contractile proteins. Thus, while neither the insulin
      receptor nor IGF-1 receptor in muscle is critical for glucose homeostasis during
      the first month of life, signaling from these receptors, particularly the insulin
      receptor, is required for normal cardiac metabolism and function.

PMID- 17189428
TI  - Ligand-specific dynamics of the androgen receptor at its response element in
      living cells.
AB  - Androgens have key roles in normal physiology and in male sexual differentiation
      as well as in pathological conditions such as prostate cancer. Androgens act
      through the androgen receptor (AR), which is a ligand-modulated transcription
      factor. Antiandrogens block AR function and are widely used in disease states,
      but little is known about their mechanism of action in vivo. Here, we describe a
      rapid differential interaction of AR with target genomic sites in living cells in
      the presence of agonists which coincides with the recruitment of BRM ATPase
      complex and chromatin remodeling, resulting in transcriptional activation. In
      contrast, the interaction of antagonist-bound or mutant AR with its target was
      found to be kinetically different: it was dramatically faster, occurred without
      chromatin remodeling, and resulted in the lack of transcriptional inhibition.
      Fluorescent resonance energy transfer analysis of wild-type AR and a
      transcriptionally compromised mutant at the hormone response element showed that
      intramolecular interactions between the N and C termini of AR play a key
      functional role in vivo compared to intermolecular interactions between two
      neighboring ARs. These data provide a kinetic and mechanistic basis for
      regulation of gene expression by androgens and antiandrogens in living cells.

PMID- 17189429
TI  - Reduced levels of ATF-2 predispose mice to mammary tumors.
AB  - Transcription factor ATF-2 is a nuclear target of stress-activated protein
      kinases, such as p38, which are activated by various extracellular stresses,
      including UV light. Here, we show that ATF-2 plays a critical role in hypoxia-
      and high-cell-density-induced apoptosis and the development of mammary tumors.
      Compared to wild-type cells, Atf-2(-/-) mouse embryonic fibroblasts (MEFs) were
      more resistant to hypoxia- and anisomycin-induced apoptosis but remained equally
      susceptible to other stresses, including UV. Atf-2(-/-) and Atf-2(+/-) MEFs could
      not express a group of genes, such as Gadd45alpha, whose overexpression can
      induce apoptosis, in response to hypoxia. Atf-2(-/-) MEFs also had a higher
      saturation density than wild-type cells and expressed lower levels of Maspin, the
      breast cancer tumor suppressor, which is also known to enhance cellular
      sensitivity to apoptotic stimuli. Atf-2(-/-) MEFs underwent a lower degree of
      apoptosis at high cell density than wild-type cells. Atf-2(+/-) mice were highly
      prone to mammary tumors that expressed reduced levels of Gadd45alpha and Maspin.
      The ATF-2 mRNA levels in human breast cancers were lower than those in normal
      breast tissue. Thus, ATF-2 acts as a tumor susceptibility gene of mammary tumors,
      at least partly, by activating a group of target genes, including Maspin and
      Gadd45alpha.

PMID- 17189430
TI  - Genome-wide redistribution of meiotic double-strand breaks in Saccharomyces
      cerevisiae.
AB  - Meiotic recombination is initiated by the formation of programmed DNA double
      strand breaks (DSBs) catalyzed by the Spo11 protein. DSBs are not randomly
      distributed along chromosomes. To better understand factors that control the
      distribution of DSBs in budding yeast, we have examined the genome-wide binding
      and cleavage properties of the Gal4 DNA binding domain (Gal4BD)-Spo11 fusion
      protein. We found that Gal4BD-Spo11 cleaves only a subset of its binding sites,
      indicating that the association of Spo11 with chromatin is not sufficient for DSB
      formation. In centromere-associated regions, the centromere itself prevents DSB
      cleavage by tethered Gal4BD-Spo11 since its displacement restores targeted DSB
      formation. In addition, we observed that new DSBs introduced by Gal4BD-Spo11
      inhibit surrounding DSB formation over long distances (up to 60 kb), keeping
      constant the number of DSBs per chromosomal region. Together, these results
      demonstrate that the targeting of Spo11 to new chromosomal locations leads to
      both local stimulation and genome-wide redistribution of recombination initiation
      and that some chromosomal regions are inherently cold regardless of the presence
      of Spo11.

PMID- 17189431
TI  - Telomere rapid deletion regulates telomere length in Arabidopsis thaliana.
AB  - Telomere length is maintained in species-specific equilibrium primarily through a
      competition between telomerase-mediated elongation and the loss of terminal DNA
      through the end-replication problem. Recombinational activities are also capable
      of both lengthening and shortening telomeres. Here we demonstrate that elongated
      telomeres in Arabidopsis Ku70 mutants reach a new length set point after three
      generations. Restoration of wild-type Ku70 in these mutants leads to discrete
      telomere-shortening events consistent with telomere rapid deletion (TRD). These
      findings imply that the longer telomere length set point is achieved through
      competition between overactive telomerase and TRD. Surprisingly, in the absence
      of telomerase, a subset of elongated telomeres was further lengthened, suggesting
      that in this background a mechanism of telomerase-independent lengthening of
      telomeres operates. Unexpectedly, we also found that plants possessing wild-type
      length telomeres exhibit TRD when telomerase is inactivated. TRD is stochastic,
      and all chromosome ends appear to be equally susceptible. The frequency of TRD
      decreases as telomeres shorten; telomeres less than 2 kb in length are rarely
      subject to TRD. We conclude that TRD functions as a potent force to regulate
      telomere length in Arabidopsis.

PMID- 17189432
TI  - Development of signature-tagged mutagenesis in Burkholderia pseudomallei to
      identify genes important in survival and pathogenesis.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, is an important
      human pathogen in Southeast Asia and northern Australia for which a vaccine is
      unavailable. A panel of 892 double signature-tagged mutants was screened for
      virulence using an intranasal BALB/c mouse model of infection. A novel DNA tag
      microarray identified 33 mutants as being attenuated in spleens, while 6 were
      attenuated in both lungs and spleens. The transposon insertion sites in spleen
      attenuated mutants revealed genes involved in several stages of capsular
      polysaccharide biosynthesis and DNA replication and repair, a putative
      oxidoreductase, ABC transporters, and a lipoprotein that may be important in
      intercellular spreading. The six mutants identified as missing in both lungs and
      spleens were found to have insertions in recA involved in the SOS response and
      DNA repair; putative auxotrophs of leucine, threonine, p-aminobenzoic acid, and a
      mutant with an insertion in aroB causing auxotrophy for aromatic compounds were
      also found. Murine challenge studies revealed partial protection in BALB/c mice
      vaccinated with the aroB mutant. The refined signature-tagged mutagenesis
      approach developed in this study was used to efficiently identify attenuating
      mutants from this highly pathogenic species and could be applied to other
      organisms.

PMID- 17189433
TI  - Retention of virulence in a viable but nonculturable Edwardsiella tarda isolate.
AB  - Edwardsiella tarda is pathogen of fish and other animals. The aim of this study
      was to investigate the viable but nonculturable (VBNC) state and virulence
      retention of this bacterium. Edwardsiella tarda CW7 was cultured in sterilized
      aged seawater at 4 degrees C. Total cell counts remained constant throughout the
      28-day period by acridine orange direct counting, while plate counts declined to
      undetectable levels (<0.1 CFU/ml) within 28 days by plate counting. The direct
      viable counts, on the other hand, declined to ca. 10(9) CFU/ml active cells and
      remained fairly constant at this level by direct viable counting. These results
      indicated that a large population of cells existed in a viable but nonculturable
      state. VBNC E. tarda CW7 could resuscitate in experimental chick embryos and in
      the presence of nutrition with a temperature upshift. The resuscitative times
      were 6 days and 8 days, respectively. The morphological changes of VBNC, normal,
      and resuscitative E. tarda CW7 cells were studied with a scanning electron
      microscope. The results showed that when the cells entered into the VBNC state,
      they gradually changed in shape from short rods to coccoid and decreased in size,
      but the resuscitative cells did not show any obvious differences from the normal
      cells. The VBNC and the resuscitative E. tarda CW7 cells were intraperitoneally
      inoculated into turbot separately, and the fish inoculated with the resuscitative
      cells died within 7 days, which suggested that VBNC E. tarda CW7 might retain
      pathogenicity.

PMID- 17189434
TI  - Biodiversity of bacterial ecosystems in traditional Egyptian Domiati cheese.
AB  - Bacterial biodiversity occurring in traditional Egyptian soft Domiati cheese was
      studied by PCR-temporal temperature gel electrophoresis (TTGE) and PCR-denaturing
      gradient gel electrophoresis (DGGE). Bands were identified using a reference
      species database (J.-C. Ogier et al., Appl. Environ. Microbiol. 70:5628-5643,
      2004); de novo bands having nonidentified migration patterns were identified by
      DNA sequencing. Results reveal a novel bacterial profile and extensive bacterial
      biodiversity in Domiati cheeses, as reflected by the numerous bands present in
      TTGE and DGGE patterns. The dominant lactic acid bacteria (LAB) identified were
      as follows: Leuconostoc mesenteroides, Lactococcus garvieae, Aerococcus viridans,
      Lactobacillus versmoldensis, Pediococcus inopinatus, and Lactococcus lactis.
      Frequent non-LAB species included numerous coagulase-negative staphylococci,
      Vibrio spp., Kocuria rhizophila, Kocuria kristinae, Kocuria halotolerans,
      Arthrobacter spp./Brachybacterium tyrofermentans. This is the first time that the
      majority of these species has been identified in Domiati cheese. Nearly all the
      dominant and frequent bacterial species are salt tolerant, and several correspond
      to known marine bacteria. As Domiati cheese contains 5.4 to 9.5% NaCl, we suggest
      that these bacteria are likely to have an important role in the ripening process.
      This first systematic study of the microbial composition of Domiati cheeses
      reveals great biodiversity and evokes a role for marine bacteria in determining
      cheese type.

PMID- 17189436
TI  - Development and evaluation of methods to detect nucleopolyhedroviruses in larvae
      of the Douglas-fir tussock moth, Orgyia pseudotsugata (McDunnough).
AB  - Various molecular methods are used to detect pathogenic microorganisms and
      viruses within their hosts, but these methods are rarely validated by direct
      comparison. Southern hybridization, enzyme-linked immunosorbent assay (ELISA),
      and a novel DNA extraction/PCR assay were used to detect Orgyia pseudotsugata
      multiple nucleopolyhedrovirus (OpMNPV) in Douglas-fir tussock moth larvae. PCR
      was more sensitive than Southern hybridization and ELISA at detecting
      semipurified virus. ELISA, however, was the most accurate method for detecting
      virus within larvae, given that Southern hybridization and PCR produced false
      negative results (31% and 2.5%, respectively). ELISA may be preferable in some
      applications because virus infections can be quantified (r(2) = 0.995). These
      results may be applicable to both applied and academic research that seeks to
      accurately identify the incidence of viruses and microorganisms that regulate
      insect populations.

PMID- 17189435
TI  - Hydrogen metabolism in Shewanella oneidensis MR-1.
AB  - Shewanella oneidensis MR-1 is a facultative sediment microorganism which uses
      diverse compounds, such as oxygen and fumarate, as well as insoluble Fe(III) and
      Mn(IV) as electron acceptors. The electron donor spectrum is more limited and
      includes metabolic end products of primary fermenting bacteria, such as lactate,
      formate, and hydrogen. While the utilization of hydrogen as an electron donor has
      been described previously, we report here the formation of hydrogen from pyruvate
      under anaerobic, stationary-phase conditions in the absence of an external
      electron acceptor. Genes for the two S. oneidensis MR-1 hydrogenases, hydA,
      encoding a periplasmic [Fe-Fe] hydrogenase, and hyaB, encoding a periplasmic [Ni
      Fe] hydrogenase, were found to be expressed only under anaerobic conditions
      during early exponential growth and into stationary-phase growth. Analyses of
      DeltahydA, DeltahyaB, and DeltahydA DeltahyaB in-frame-deletion mutants indicated
      that HydA functions primarily as a hydrogen-forming hydrogenase while HyaB has a
      bifunctional role and represents the dominant hydrogenase activity under the
      experimental conditions tested. Based on results from physiological and genetic
      experiments, we propose that hydrogen is formed from pyruvate by multiple
      parallel pathways, one pathway involving formate as an intermediate, pyruvate
      formate lyase, and formate-hydrogen lyase, comprised of HydA hydrogenase and
      formate dehydrogenase, and a formate-independent pathway involving pyruvate
      dehydrogenase. A reverse electron transport chain is potentially involved in a
      formate-hydrogen lyase-independent pathway. While pyruvate does not support a
      fermentative mode of growth in this microorganism, pyruvate, in the absence of an
      electron acceptor, increased cell viability in anaerobic, stationary-phase
      cultures, suggesting a role in the survival of S. oneidensis MR-1 under
      stationary-phase conditions.

PMID- 17189437
TI  - Rugosity in Grimontia hollisae.
AB  - Grimontia hollisae, formerly Vibrio hollisae, produces both smooth and rugose
      colonial variants. The rugose colony phenotype is characterized by wrinkled
      colonies producing copious amounts of exopolysaccharide. Cells from a rugose
      colony grown at 30 degrees C form rugose colonies, while the same cells grown at
      37 degrees C form smooth colonies, which are characterized by a nonwrinkled,
      uncrannied appearance. Stress response studies revealed that after exposure to
      bleach for 30 min, rugose survivors outnumbered smooth survivors. Light scatter
      information obtained by flow cytometry indicated that rugose cells clumped into
      clusters of three or more cells (average, five cells) and formed two major
      clusters, while smooth cells formed only one cluster of single cells or doublets.
      Fluorescent lectin-binding flow cytometry studies revealed that the percentages
      of rugose cells that bound either wheat germ agglutinin (WGA) or Galanthus
      nivalis lectin (GNL) were greater than the percentages of smooth cells that bound
      the same lectins (WGA, 35% versus 3.5%; GNL, 67% versus 0.21%). These results
      indicate that the rugose exopolysaccharide consists partially of N
      acetylglucosamine and mannose. Rugose colonies produced significantly more
      biofilm material than did smooth colonies, and rugose colonies grown at 30
      degrees C produced more biofilm material than rugose colonies grown at 37 degrees
      C. Ultrastructurally, rugose colonies show regional cellular differentiation,
      with apical and lateral colonial regions containing cells embedded in a matrix
      stained by Alcian Blue. The cells touching the agar surface are packed tightly
      together in a palisade-like manner. The central region of the colony contains
      irregularly arranged, fluid-filled spaces and loosely packed chains or arrays of
      coccoid and vibrioid cells. Smooth colonies, in contrast, are flattened, composed
      of vibrioid cells, and lack distinct regional cellular differences. Results from
      suckling mouse studies showed that both orally fed rugose and smooth variants
      elicited significant, but similar, amounts of fluid accumulated in the stomach
      and intestines. These observations comprise the first report of expression and
      characterization of rugosity by G. hollisae and raise the possibility that
      expression of rugose exopolysaccharide in this organism is regulated at least in
      part by growth temperature.

PMID- 17189439
TI  - Biogeography, host specificity, and molecular phylogeny of the basidiomycetous
      yeast Phaffia rhodozyma and its sexual form, Xanthophyllomyces dendrorhous.
AB  - Phaffia rhodozyma (sexual form, Xanthophyllomyces dendrorhous) is a
      basidiomycetous yeast that has been found in tree exudates in the Northern
      Hemisphere at high altitudes and latitudes. This yeast produces astaxanthin, a
      carotenoid pigment with biotechnological importance because it is used in
      aquaculture for fish pigmentation. We isolated X. dendrorhous from the Southern
      Hemisphere (Patagonia, Argentina), where it was associated with fruiting bodies
      of Cyttaria hariotii, an ascomycetous parasite of Nothofagus trees. We compared
      internal transcribed spacer (ITS)-based phylogenies of P. rhodozyma and its tree
      host (Betulaceae, Corneaceae, Fagaceae, and Nothofagaceae) and found them to be
      generally concordant, suggesting that different yeast lineages colonize different
      trees and providing an explanation for the phylogenetic distance observed between
      the type strains of P. rhodozyma and X. dendrorhous. We hypothesize that the
      association of Xanthophyllomyces with Cyttaria derives from a previous
      association of the yeast with Nothofagus, and the sister relationship between
      Nothofagaceae and Betulaceae plus Fagaceae correlates with the phylogeny of X.
      dendrorhous strains originating from these three plant families. The two most
      basal strains of X. dendrorhous are those isolated from Cornus, an ancestral
      genus in the phylogenetic analysis of the host trees. Thus, we question previous
      conclusions that P. rhodozyma and X. dendrorhous represent different species
      since the polymorphisms detected in the ITS and intergenic spacer sequences can
      be attributed to intraspecific variation associated with host specificity. Our
      study provides a deeper understanding of Phaffia biogeography, ecology, and
      molecular phylogeny. Such knowledge is essential for the comprehension of many
      aspects of the biology of this organism and will facilitate the study of
      astaxanthin production within an evolutionary and ecological framework.

PMID- 17189438
TI  - Synthesis and selection of de novo proteins that bind and impede cellular
      functions of an essential mycobacterial protein.
AB  - Recent advances in nonrational and part-rational approaches to de novo
      peptide/protein design have shown increasing potential for development of novel
      peptides and proteins of therapeutic use. We demonstrated earlier the usefulness
      of one such approach recently developed by us, called "codon shuffling," in
      creating stand-alone de novo protein libraries from which bioactive proteins
      could be isolated. Here, we report the synthesis and selection of codon-shuffled
      de novo proteins that bind to a selected Mycobacterium tuberculosis protein
      target, the histone-like protein HupB, believed to be essential for mycobacterial
      growth. Using a versatile bacterial two-hybrid system that entailed utilization
      of HupB and various codon-shuffled protein libraries as bait and prey,
      respectively, we were able to identify proteins that bound strongly to HupB. The
      observed interaction was also confirmed using an in vitro assay. One of the
      protein binders was expressed in Mycobacterium smegmatis and was shown to
      appreciably affect growth in the exponential phase, a period wherein HupB is
      selectively expressed. Furthermore, the transcription profile of hupB gene showed
      a significant reduction in the transcript quantity in mycobacterial strains
      expressing the protein binder. Electron microscopy of the affected mycobacteria
      elaborated on the extent of cell damage and hinted towards a cell division
      malfunction. It is our belief that a closer inspection of the obtained de novo
      proteins may bring about the generation of small-molecule analogs,
      peptidomimetics, or indeed the proteins themselves as realistic leads for drug
      candidates. Furthermore, our strategy is adaptable for large-scale targeting of
      the essential protein pool of Mycobacterium tuberculosis and other pathogens.

PMID- 17189440
TI  - Transgalactosylation in a water-solvent biphasic reaction system with beta
      galactosidase displayed on the surfaces of Bacillus subtilis spores.
AB  - The ever-increasing industrial demand for biocatalysis necessitates innovations
      in the preparation and stabilization of biocatalysts. In this study, we
      demonstrated that beta-galactosidase (beta-Gal) displayed on Bacillus spores by
      fusion to the spore coat proteins (CotG) may be used as a whole-cell immobilized
      biocatalyst for transgalactosylation in water-solvent biphasic reaction systems.
      The resulting spores had a specific hydrolytic activity of 5 x 10(3) U/g (dry
      weight) of spores. The beta-Gal was tightly attached to the spore surface and was
      more stable in the presence of various organic solvents than its native form was.
      The thermostability of the spore-displayed enzyme was also increased, and the
      enzyme was further stabilized by chemically cross-linking it with glutaraldehyde.
      With spore-displayed beta-Gal, octyl-beta-D-galactopyranoside was synthesized at
      concentrations up to 27.7 mM (8.1 g/liter) with a conversion yield of 27.7%
      (wt/wt) after 24 h from 100 mM lactose and 100 mM octanol dissolved in phosphate
      buffer and ethyl ether, respectively. Interestingly, the spores were found to
      partition mainly at the interface between the water and solvent phases, and they
      were more available to catalysis between the two phases, as determined by light
      microscopy and confocal fluorescence microscopy. We propose that spore display
      not only offers a new and facile way to construct robust biocatalysts but also
      provides a novel basis for phase transfer biocatalytic processes.

PMID- 17189442
TI  - A novel high-throughput screen reveals yeast genes that increase secretion of
      heterologous proteins.
AB  - The yeast Saccharomyces cerevisiae is an attractive host for the production of
      heterologous proteins. However, low-yield production of many proteins (from
      micrograms to milligrams/liter) leaves considerable room for optimization. By
      engineering the yeast cell via traceable genome-wide libraries, genes that can
      enhance protein expression level because of their roles in protein transcription,
      translation, folding, and trafficking processes can be readily identified. This
      report details a novel approach that combines yeast cDNA overexpression libraries
      with yeast surface display to allow the rapid flow cytometric screening of
      engineered yeast for gene products that improve the display of heterologous
      proteins. After optimization of the screening conditions, a genome-wide scan
      yielded five yeast gene products that promoted increased display levels of a
      single-chain T-cell receptor (scTCR). The display-enhancing genes included those
      coding for cell wall proteins (CCW12, CWP2, and SED1), a ribosomal subunit
      protein (RPP0), and an endoplasmic reticulum-resident protein (ERO1). Under the
      premise that yeast surface display levels could be used as a predictor of
      secretion efficiency, each display-enhancing gene product was tested for its
      ability to affect secretion levels of multiple scTCR and single-chain antibodies
      (scFv). All of the selected yeast gene products were shown to promote increased
      secretion of active protein (1.5-fold to 7.9-fold), with CCW12 and ERO1 being the
      most generalizable enhancers of scFv/scTCR secretion.

PMID- 17189443
TI  - Evolutionary dynamics of Ralstonia solanacearum.
AB  - We investigated the genetic diversity, extent of recombination, natural
      selection, and population divergence of Ralstonia solanacearum samples obtained
      from sources worldwide. This plant pathogen causes bacterial wilt in many crops
      and constitutes a serious threat to agricultural production due to its very wide
      host range and aggressiveness. Five housekeeping genes, dispersed around the
      chromosome, and three virulence-related genes, located on the megaplasmid, were
      sequenced from 58 strains belonging to the four major phylogenetic clusters
      (phylotypes). Whereas genetic variation is high and consistent for all
      housekeeping loci studied, virulence-related gene sequences are more diverse.
      Phylogenetic and statistical analyses suggest that this organism is a highly
      diverse bacterial species containing four major, deeply separated evolutionary
      lineages (phylotypes I to IV) and a weaker subdivision of phylotype II into two
      subgroups. Analysis of molecular variations showed that the geographic isolation
      and spatial distance have been the significant determinants of genetic variation
      between phylotypes. R. solanacearum displays high clonality for housekeeping
      genes in all phylotypes (except phylotype III) and significant levels of
      recombination for the virulence-related egl and hrpB genes, which are limited
      mainly to phylotype strains III and IV. Finally, genes essential for species
      survival are under purifying selection, and those directly involved in
      pathogenesis might be under diversifying selection.

PMID- 17189441
TI  - Global effect of indole-3-acetic acid biosynthesis on multiple virulence factors
      of Erwinia chrysanthemi 3937.
AB  - Production of the plant hormone indole-3-acetic acid (IAA) is widespread among
      plant-associated microorganisms. The non-gall-forming phytopathogen Erwinia
      chrysanthemi 3937 (strain Ech3937) possesses iaaM (ASAP16562) and iaaH
      (ASAP16563) gene homologues. In this work, the null knockout iaaM mutant strain
      Ech138 was constructed. The IAA production by Ech138 was reduced in M9 minimal
      medium supplemented with l-tryptophan. Compared with wild-type Ech3937, Ech138
      exhibited reduced ability to produce local maceration, but its multiplication in
      Saintpaulia ionantha was unaffected. The pectate lyase production of Ech138 was
      diminished. Compared with wild-type Ech3937, the expression levels of an
      oligogalacturonate lyase gene, ogl, and three endopectate lyase genes, pelD,
      pelI, and pelL, were reduced in Ech138 as determined by a green fluorescent
      protein-based fluorescence-activated cell sorting promoter activity assay. In
      addition, the transcription of type III secretion system (T3SS) genes, dspE (a
      putative T3SS effector) and hrpN (T3SS harpin), was found to be diminished in the
      iaaM mutant Ech138. Compared with Ech3937, reduced expression of hrpL (a T3SS
      alternative sigma factor) and gacA but increased expression of rsmA in Ech138 was
      also observed, suggesting that the regulation of T3SS and pectate lyase genes by
      IAA biosynthesis might be partially due to the posttranscriptional regulation of
      the Gac-Rsm regulatory pathway.

PMID- 17189444
TI  - The absence of intervening sequences in 23S rRNA genes of Campylobacter coli
      isolates from Turkeys is a unique attribute of a cluster of related strains which
      also lack resistance to erythromycin.
AB  - Certain Campylobacter strains harbor a transcribed intervening sequence (IVS) in
      their 23S rRNA genes. Following transcription, the IVS is excised, leading to
      fragmentation of the 23S rRNA. The origin and possible functions of the IVS are
      unknown. Furthermore, the distribution of IVS-harboring strains within
      Campylobacter populations is poorly understood. In this study, 104 strains of
      Campylobacter coli from turkeys, representing 27 different multilocus sequence
      typing-based sequence types (STs), were characterized in terms of IVS content and
      erythromycin susceptibility. Sixty-nine strains harbored IVSs in all three 23S
      rRNA genes, whereas the other 35 strains lacked IVSs from at least one of the
      genes. The STs of the latter strains belonged to an unusual cluster of C. coli
      STs (cluster II), earlier found primarily in turkey strains and characterized by
      the presence of the C. jejuni aspA103 allele. The majority (66/69) of strains
      harboring IVSs in all three 23S rRNA genes were resistant to erythromycin,
      whereas none of the 35 strains with at least one IVS-free 23S rRNA gene were
      resistant. Cluster II strains could be transformed to erythromycin resistance
      with genomic DNA from C. coli that harbored IVS and the A2075G transition in the
      23S rRNA gene, associated with resistance to erythromycin in Campylobacter.
      Erythromycin-resistant transformants harbored both the A2075 transition and IVS.
      The findings suggest that the absence of IVS in C. coli from turkeys is
      characteristic of a unique clonal group of erythromycin-susceptible strains and
      that IVS can be acquired by these strains via natural transformation to
      erythromycin resistance.

PMID- 17189445
TI  - Influences of infaunal burrows on the community structure and activity of ammonia
      oxidizing bacteria in intertidal sediments.
AB  - Influences of infaunal burrows constructed by the polychaete (Tylorrhynchus
      heterochaetus) on O(2) concentrations and community structures and abundances of
      ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) in
      intertidal sediments were analyzed by the combined use of a 16S rRNA gene-based
      molecular approach and microelectrodes. The microelectrode measurements performed
      in an experimental system developed in an aquarium showed direct evidence of O(2)
      transport down to a depth of 350 mm of the sediment through a burrow. The 16S
      rRNA gene-cloning analysis revealed that the betaproteobacterial AOB communities
      in the sediment surface and the burrow walls were dominated by Nitrosomonas sp.
      strain Nm143-like sequences, and most of the clones in Nitrospira-like NOB clone
      libraries of the sediment surface and the burrow walls were related to the
      Nitrospira marina lineage. Furthermore, we investigated vertical distributions of
      AOB and NOB in the infaunal burrow walls and the bulk sediments by real-time
      quantitative PCR (Q-PCR) assay. The AOB and Nitrospira-like NOB-specific 16S rRNA
      gene copy numbers in the burrow walls were comparable with those in the sediment
      surfaces. These numbers in the burrow wall at a depth of 50 to 55 mm from the
      surface were, however, higher than those in the bulk sediment at the same depth.
      The microelectrode measurements showed higher NH(4)(+) consumption activity at
      the burrow wall than those at the surrounding sediment. This result was
      consistent with the results of microcosm experiments showing that the consumption
      rates of NH(4)(+) and total inorganic nitrogen increased with increasing infaunal
      density in the sediment. These results clearly demonstrated that the infaunal
      burrows stimulated O(2) transport into the sediment in which otherwise reducing
      conditions prevailed, resulting in development of high NH(4)(+) consumption
      capacity. Consequently, the infaunal burrow became an important site for NH(4)(+)
      consumption in the intertidal sediment.

PMID- 17189446
TI  - Mechanism of resistance to Bacillus thuringiensis toxin Cry1Ac in a greenhouse
      population of the cabbage looper, Trichoplusia ni.
AB  - The cabbage looper, Trichoplusia ni, is one of only two insect species that have
      evolved resistance to Bacillus thuringiensis in agricultural situations. The
      trait of resistance to B. thuringiensis toxin Cry1Ac from a greenhouse-evolved
      resistant population of T. ni was introgressed into a highly inbred susceptible
      laboratory strain. The resulting introgression strain, GLEN-Cry1Ac-BCS, and its
      nearly isogenic susceptible strain were subjected to comparative genetic and
      biochemical studies to determine the mechanism of resistance. Results showed that
      midgut proteases, hemolymph melanization activity, and midgut esterase were not
      altered in the GLEN-Cry1Ac-BCS strain. The pattern of cross-resistance of the
      GLEN-Cry1Ac-BCS strain to 11 B. thuringiensis Cry toxins showed a correlation of
      the resistance with the Cry1Ab/Cry1Ac binding site in T. ni. This cross
      resistance pattern is different from that found in a previously reported
      laboratory-selected Cry1Ab-resistant T. ni strain, evidently indicating that the
      greenhouse-evolved resistance involves a mechanism different from the laboratory
      selected resistance. Determination of specific binding of B. thuringiensis toxins
      Cry1Ab and Cry1Ac to the midgut brush border membranes confirmed the loss of
      midgut binding to Cry1Ab and Cry1Ac in the resistant larvae. The loss of midgut
      binding to Cry1Ab/Cry1Ac is inherited as a recessive trait, which is consistent
      with the recessive inheritance of Cry1Ab/Cry1Ac resistance in this greenhouse
      derived T. ni population. Therefore, it is concluded that the mechanism for the
      greenhouse-evolved Cry1Ac resistance in T. ni is an alteration affecting the
      binding of Cry1Ab and Cry1Ac to the Cry1Ab/Cry1Ac binding site in the midgut.

PMID- 17189447
TI  - Reduced dietary intake of carbohydrates by obese subjects results in decreased
      concentrations of butyrate and butyrate-producing bacteria in feces.
AB  - Weight loss diets for humans that are based on a high intake of protein but low
      intake of fermentable carbohydrate may alter microbial activity and bacterial
      populations in the large intestine and thus impact on gut health. In this study,
      19 healthy, obese (body mass index range, 30 to 42) volunteers were given in
      succession three different diets: maintenance (M) for 3 days (399 g
      carbohydrate/day) and then high protein/medium (164 g/day) carbohydrate (HPMC)
      and high protein/low (24 g/day) carbohydrate (HPLC) each for 4 weeks. Stool
      samples were collected at the end of each dietary regimen. Total fecal short
      chain fatty acids were 114 mM, 74 mM, and 56 mM (P < 0.001) for M, HPMC, and HPLC
      diets, respectively, and there was a disproportionate reduction in fecal butyrate
      (18 mM, 9 mM, and 4 mM, respectively; P < 0.001) with decreasing carbohydrate.
      Major groups of fecal bacteria were monitored using nine 16S rRNA-targeted
      fluorescence in situ hybridization probes, relative to counts obtained with the
      broad probe Eub338. No significant change was seen in the relative counts of the
      bacteroides (Bac303) (mean, 29.6%) or the clostridial cluster XIVa (Erec482,
      23.3%), cluster IX (Prop853, 9.3%), or cluster IV (Fprau645, 11.6%; Rbro730 plus
      Rfla729, 9.3%) groups. In contrast, the Roseburia spp. and Eubacterium rectale
      subgroup of cluster XIVa (11%, 8%, and 3% for M, HPMC, and HPLC, respectively; P
      < 0.001) and bifidobacteria (4%, 2.1%, and 1.9%, respectively; P = 0.026)
      decreased as carbohydrate intake decreased. The abundance of butyrate-producing
      bacteria related to Roseburia spp. and E. rectale correlated well with the
      decline in fecal butyrate.

PMID- 17189448
TI  - Escherichia coli O157:H7 colonization at the rectoanal junction of long-duration
      culture-positive cattle.
AB  - Long-duration consistently Escherichia coli O157:H7 culture-positive cattle were
      euthanized and necropsied. Tissue and digesta from along the gastrointestinal
      tract (GIT) were cultured for the bacteria and examined histologically for
      lymphoid character. E. coli O157:H7 was detected only at the rectoanal junction
      mucosa and not at any other GIT location.

PMID- 17189451
TI  - The use of GIS to evaluate traffic-related pollution.

PMID- 17189449
TI  - Characterization of strong promoters from an environmental Flavobacterium
      hibernum strain by using a green fluorescent protein-based reporter system.
AB  - We developed techniques for the genetic manipulation of Flavobacterium species
      and used it to characterize several promoters found in these bacteria. Our
      studies utilized Flavobacterium hibernum strain W22, an environmental strain we
      isolated from tree hole habitats of mosquito larvae. Plasmids from F. hibernum
      strain W22 were more efficiently (approximately 1,250-fold) transferred by
      electroporation into F. hibernum strain W22 than those isolated from Escherichia
      coli, thus indicating that an efficient restriction barrier exists between these
      species. The strong promoter, tac, functional in proteobacteria, did not function
      in Flavobacterium strains. Therefore, a promoter-trap plasmid, pSCH03, containing
      a promoterless gfpmut3 gene was constructed. A library of 9,000 clones containing
      chromosomal fragments of F. hibernum strain W22 in pSCH03 was screened for their
      ability to drive expression of the promoterless gfpmut3 gene. Twenty strong
      promoters were used for further study. The transcription start points were
      determined from seven promoter clones by the 5' rapid amplification of cDNA ends
      technique. Promoter consensus sequences from Flavobacterium were identified as
      TAnnTTTG and TTG, where n is any nucleotide, centered approximately 7 and 33 bp
      upstream of the transcription start site, respectively. A putative novel ribosome
      binding site consensus sequence is proposed as TAAAA by aligning the 20-bp
      regions upstream of the translational start site in 25 genes. Our primary results
      demonstrate that at least some promoter and ribosome binding site motifs of
      Flavobacterium strains are unusual within the bacterial domain and suggest an
      early evolutionary divergence of this bacterial group. The techniques presented
      here allow for more detailed genetics-based studies and analyses of
      Flavobacterium species in the environment.

PMID- 17189450
TI  - Identification and cultivation of anaerobic, syntrophic long-chain fatty acid
      degrading microbes from mesophilic and thermophilic methanogenic sludges.
AB  - We investigated long-chain fatty acid (LCFA)-degrading anaerobic microbes by
      enrichment, isolation, and RNA-based stable isotope probing (SIP). Primary
      enrichment cultures were made with each of four LCFA substrates (palmitate,
      stearate, oleate, or linoleate, as the sole energy source) at 55 degrees C or 37
      degrees C with two sources of anaerobic granular sludge as the inoculum. After
      several transfers, we obtained seven stable enrichment cultures in which LCFAs
      were converted to methane. The bacterial populations in these cultures were then
      subjected to 16S rRNA gene-based cloning, in situ hybridization, and RNA-SIP. In
      five of seven enrichment cultures, the predominant bacteria were affiliated with
      the family Syntrophomonadaceae. The other two enrichment cultures contained
      different bacterial populations in which the majority of members belonged to the
      phylum Firmicutes and the class Deltaproteobacteria. After several attempts to
      isolate these dominant bacteria, strain MPA, belonging to the family
      Syntrophomonadaceae, and strain TOL, affiliated with the phylum Firmicutes, were
      successfully isolated. Strain MPA converts palmitate to acetate and methane in
      syntrophic association with Methanospirillum hungatei. Even though strain TOL
      assimilated [(13)C]palmitate in the original enrichment culture, strain TOL has
      not shown the ability to degrade LCFAs after isolation. These results suggest
      that microbes involved in the degradation of LCFAs under methanogenic conditions
      might not belong only to the family Syntrophomonadaceae, as most anaerobic LCFA
      degrading microbes do, but may also be found in phylogenetically diverse
      bacterial groups.

PMID- 17189452
TI  - Death stroked by dusty air: more mysteries to be solved.

PMID- 17189453
TI  - Non-Hodgkin lymphoma and occupational exposures: multiple exposures not =
      multiple papers.

PMID- 17189454
TI  - Cancer risk in the semiconductor industry: responding to the call for action.

PMID- 17189457
TI  - Nature of symbiosis in oral disease.

PMID- 17189455
TI  - The chlorine hypothesis: fact or fiction?

PMID- 17189458
TI  - Remodeling the dentofacial skeleton: the biological basis of orthodontics and
      dentofacial orthopedics.
AB  - Orthodontic tooth movement is dependent upon the remodeling of the periodontal
      ligament and alveolar bone by mechanical means. Facial sutures are also fibrous
      articulations, and by remodeling these joints, one can alter the positional
      relationships of the bones of the facial skeleton. As might be expected from the
      structure and mobility of the temporomandibular joint (TMJ), this articulation is
      more resistant to mechanical deformation, and whether functional mandibular
      displacement can alter the growth of the condyle remains controversial. Clinical
      investigations of the effects of the Andresen activator and its variants on
      dentofacial growth suggest that the changes are essentially dento-alveolar.
      However, with the popularity of active functional appliances, such as the Herbst
      and twin-block based on 'jumping the bite', attention has focused on how they
      achieve dentofacial change. Animal experimentation enables informed decisions to
      be made regarding the effects of orthodontic treatment on the facial skeleton at
      the tissue, cellular, and molecular levels. Both rat and monkey models have been
      widely used, and the following conclusions can be drawn from such
      experimentation: (1) Facial sutures readily respond to changes in their
      mechanical environment; (2) anterior mandibular displacement in rat models does
      not increase the mitotic activity of cells within the condyle to be of clinical
      significance, and (3) mandibular displacement in non-human primates initiates
      remodeling activity within the TMJ and can alter condylar growth direction. This
      last conclusion may have clinical utility, particularly in an actively growing
      child.

PMID- 17189459
TI  - Hereditary gingival fibromatosis: characteristics and novel putative pathogenic
      mechanisms.
AB  - Hereditary gingival fibromatosis (HGF) is a rare condition that can occur as an
      isolated disease or as part of a syndrome or chromosomal abnormality. In severe
      cases, the gingival enlargement may cover the crowns of teeth and cause severe
      functional and esthetic concerns. Histological and cell culture studies have
      uncovered some of the molecular and cellular changes associated with HGF.
      However, the pathogenesis of the disease is still largely unknown. Recent studies
      about the genetic characteristics of HGF have provided novel clues about the
      potential pathogenic mechanisms. In particular, mutation in the son-of-sevenless
      (SOS-1) gene has been associated with one form of the disease. However, HGF
      displays genetic heterogeneity, and mutations in other genes are also likely
      involved. This review outlines the current knowledge about the histological,
      cellular, and genetic characteristics of HGF. In addition, the potential role of
      the SOS-1 molecule and related novel intracellular signaling pathways in the
      pathogenesis of HGF will be discussed.

PMID- 17189461
TI  - Enamel matrix derivative stimulates human gingival fibroblast proliferation via
      ERK.
AB  - Emdogain, a formulation of Enamel Matrix Proteins, is used clinically for
      periodontal regeneration to stimulate PDL (periodontal ligament), cementum, and
      bone formation. Its effects on gingival fibroblasts and tissue have not been
      thoroughly studied. Therefore, we investigated the mechanisms by which Emdogain
      affects the cell cycle of human gingival fibroblasts. Without serum, Emdogain (50
      microg/mL) induced human gingival fibroblast entry into the S phase and DNA
      synthesis, but not completion of the cell cycle. With low serum concentrations
      (0.2-0.5%), Emdogain synergistically induced completion of the cell cycle,
      resulting in increased cell numbers. The mitogenic response to Emdogain depended
      on Extracellular Regulated Kinase (ERK) activation, which occurred in two waves,
      peaking after 15 min and 4 to 6 hrs, since it was abolished by U0126, a specific
      MAPK inhibitor. Inhibition of the second wave was sufficient to abrogate
      mitogenesis. This study characterized the mitogenic effect of Emdogain on primary
      human gingival fibroblasts, its cooperation with serum growth factors, and the
      key mediatory role of the ERK cascade.

PMID- 17189460
TI  - Anti-P. gingivalis response correlates with atherosclerosis.
AB  - Significant associations between atherosclerosis and both Porphyromonas
      gingivalis, a major periodontopathogen, and the respiratory pathogen, Chlamydia
      pneumoniae, have been shown. Many individuals with evidence of atherosclerosis
      demonstrate seropositivity to these pathogens. The aim of the present study was
      to examine the atherogenic effect of repeated immunizations with either or both
      of these agents, and to determine if molecular mimicry of bacterial heat-shock
      protein (HSP), termed GroEL, and host (h) HSP60 was involved. Atherogenesis was
      examined in apolipoprotein-E-deficient (-/-) mice following intraperitoneal
      immunizations with P. gingivalis, C. pneumoniae, P. gingivalis, and C. pneumoniae
      or vehicle. Lesion area in the proximal aorta and levels of serum antibodies to
      P. gingivalis, C. pneumoniae, and GroEL were measured. The increased pathogen
      burden of P. gingivalis, but not of C. pneumoniae, enhanced atherosclerosis.
      hHSP60 was detected in lesions, and in P. gingivalis-immunized mice, lesion
      development was correlated with anti-GroEL antibody levels, supporting the
      involvement of molecular mimicry between GroEL and hHSP60.

PMID- 17189462
TI  - Effects of occlusal stimuli on alveolar/jaw bone formation.
AB  - Occlusion is known to influence the growth and development of the craniofacial
      complex. However, the consequences of occlusal hypofunction, or its recovery, on
      the amount of formation and development of alveolar bone and the jaw are not
      fully understood. Therefore, the present study was designed to elucidate the
      relationship between the occlusal stimuli and alveolar and jaw bone growth by the
      use of a hypofunction/recovered occlusal function model in growing rats. Bone
      histomorphometric analyses, including bone apposition rate and mineral apposition
      rate, were evaluated in double-labeled frontal sections of mandibular second
      molars. Results showed that occlusal hypofunction significantly suppressed
      alveolar and jaw bone formation compared with that in animals growing normally (p
      < 0.05). However, recovered occlusal function induced an enhancement in jaw bone
      formation. These results indicate the influence of occlusal function on alveolar
      and jaw bone formation during the growth period.

PMID- 17189463
TI  - Relationship between porotic changes in alveolar bone and spinal osteoporosis.
AB  - Epidemiological studies have shown that post-menopausal women who do not use an
      estrogen supplement have fewer teeth than those who do. We hypothesized that
      changes in the dentition of post-menopausal women might be due to alveolar bone
      alterations by estrogen deficiency. To clarify this, we analyzed the
      microstructural alveolar bone changes in ovariectomized monkeys and compared
      these with their lumbar bone mineral density. The % of baseline bone mineral
      density showed a significant decrease in the ovariectomized group as compared
      with the controls. The second-molar interradicular septa in ovariectomized
      monkeys showed a significantly decreased nodes number, cortices number, and an
      increased structural model index value. More pores were seen in the
      ovariectomized group at the top of the septa. This study demonstrated that, in
      such monkeys, estrogen deficiency led to fragility of the trabecular structure of
      the molar alveolar bone, and such fragility was inversely correlated with lumbar
      bone mineral density.

PMID- 17189464
TI  - Randomized effectiveness study of four therapeutic strategies for TMJ closed
      lock.
AB  - For individuals with temporomandibular joint (TMJ) disc displacement without
      reduction with limited mouth opening (closed lock), interventions vary from
      minimal treatment to surgery. In a single-blind trial, 106 individuals with TMJ
      closed lock were randomized among medical management, rehabilitation,
      arthroscopic surgery with post-operative rehabilitation, or arthroplasty with
      post-operative rehabilitation. Evaluations at baseline, 3, 6, 12, 18, 24, and 60
      months used the Craniomandibular Index (CMI) and Symptom Severity Index (SSI) for
      jaw function and TMJ pain respectively. Using an intention-to-treat analysis, we
      observed no between-group difference at any follow-up for CMI (p > or = 0.33) or
      SSI (p > or = 0.08). Both outcomes showed within-group improvement (p < 0.0001)
      for all groups. The findings of this study suggest that primary treatment for
      individuals with TMJ closed lock should consist of medical management or
      rehabilitation. The use of this approach will avoid unnecessary surgical
      procedures.

PMID- 17189466
TI  - A novel missense mutation (p.P52R) in amelogenin gene causing X-linked
      amelogenesis imperfecta.
AB  - Amelogenesis imperfecta (AI) is a hereditary disease with abnormal dental enamel
      formation. Here we report a Japanese family with X-linked AI transmitted over at
      least four generations. Mutation analysis revealed a novel mutation (p.P52R) in
      exon 5 of the amelogenin gene. The mutation was detected as heterozygous in
      affected females and as hemizygous in their affected father. The affected sisters
      exhibited vertical ridges on the enamel surfaces, whereas the affected father had
      thin, smooth, yellowish enamel with distinct widening of inter-dental spaces. To
      study the pathological cause underlying the disease in this family, we
      synthesized the mutant amelogenin p.P52R protein and evaluated it in vitro.
      Furthermore, we studied differences in the chemical composition between normal
      and affected teeth by x-ray diffraction analysis and x-ray fluorescence analysis.
      We believe that these results will greatly aid our understanding of the
      pathogenesis of X-linked AI.

PMID- 17189465
TI  - Influence of human jaw movement on cerebral blood flow.
AB  - Temporal changes in cerebral blood flow induced by jaw movement have yet to be
      investigated. To assess the influence of pattern and intensity of muscle
      contraction during jaw movement on task-induced change in cerebral blood flow, we
      performed bilateral transcranial Doppler ultrasound examination during clenching,
      gum chewing, and tooth tapping in healthy volunteers. A random-effects model
      analysis revealed a significant increase in middle cerebral artery blood flow
      velocity during clenching (high muscle activity) and gum chewing (moderate muscle
      activity), compared with the preceding rest period; however, such an increase was
      not detected during tooth tapping (low muscle activity). Cerebral blood flow was
      greater on the working side during the intensive isometric contraction of the
      masseter muscle in clenching. These results suggest that task-induced change in
      cerebral blood flow during jaw movement is influenced by the change in peripheral
      circulation evoked by muscle contraction.

PMID- 17189467
TI  - Smart bracket for multi-dimensional force and moment measurement.
AB  - Atraumatic, well-directed, and efficient tooth movement is interrelated with the
      therapeutic application of adequately dimensioned forces and moments in all three
      dimensions. The lack of appropriate monitoring tools inspired the development of
      an orthodontic bracket with an integrated microelectronic chip equipped with
      multiple piezoresistive stress sensors. Such a 'smart bracket' was constructed
      (scale of 2.5:1) and calibrated. To evaluate how accurately the integrated sensor
      system allowed for the quantitative determination of three-dimensional force
      moment systems externally applied to the bracket, we exerted 396 different force
      moment combinations with dimensions within usual therapeutic ranges (+/- 1.5 N
      and +/- 15 Nmm). Comparison between the externally applied force-moment
      components and those reconstructed on the basis of the stress sensor signals
      revealed very good agreement, with standard deviations in the differences of
      0.037 N and 0.985 Nmm, respectively. We conclude that our methodological approach
      is generally suitable for monitoring the relatively low forces and moments
      exerted on individual teeth with fixed orthodontic appliances.

PMID- 17189468
TI  - Effective bone engineering with periosteum-derived cells.
AB  - Bone augmentation via tissue engineering has generated significant interest. We
      hypothesized that periosteum-derived cells could be used in place of bone marrow
      stromal cells (which are widely used) in bone engineering, but the differences in
      osteogenic potential between these 2 cell types are unclear. Here, we compared
      the osteogenic potential of these cells, and investigated the optimal
      osteoinductive conditions for periosteum-derived cells. Both cell types were
      induced, via bFGF and BMP-2, to differentiate into osteoblasts. Periosteal cells
      proliferated faster than marrow stromal cells, and osteogenic markers indicated
      that bone marrow stromal cells were more osteogenic than periosteal cells.
      However, pre-treatment with bFGF made periosteal cells more sensitive to BMP-2
      and more osteogenic. Transplants of periosteal cells treated with BMP-2 after pre
      treatment with bFGF formed more new bone than did marrow stromal cells. Analysis
      of these data suggests that combined treatment with bFGF and BMP-2 can make
      periosteum a highly useful source of bone regeneration.

PMID- 17189469
TI  - Delivery mode and efficacy of BMP-2 in association with implants.
AB  - Bone healing may be improved in implant patients by the administration of
      osteogenic agents, such as bone morphogenetic protein 2 (BMP-2). But the efficacy
      of BMP-2 depends upon its mode of application. We hypothesized that BMP-2 is
      capable of a higher osteogenic efficacy when delivered physiologically, viz.,
      when incorporated into a calcium-phosphate carrier that mimics mineralized bone
      matrix, than when administered via simple pharmacological modes, such as by
      adsorption onto a carrier surface. Using an ectopic rat model, we compared the
      osteoinductive efficacies of calcium-phosphate implant-coatings bearing either
      incorporated, adsorbed, or incorporated and adsorbed BMP-2. When adsorbed
      directly onto the naked implant surface, BMP-2 was not osteogenic. When adsorbed
      onto a calcium-phosphate coating, it was osteoinductive, but not highly
      efficacious. When BMP-2 was incorporated into calcium-phosphate coatings, it was
      a potent bone-inducer, whose efficacy was compromised, not potentiated, by the
      additional deposition of an adsorbed pool.

PMID- 17189470
TI  - Chlorhexidine preserves dentin bond in vitro.
AB  - Loss of hybrid layer integrity compromises resin-dentin bond stability. Matrix
      metalloproteinases (MMPs) may be partially responsible for hybrid layer
      degradation. Since chlorhexidine inhibits MMPs, we hypothesized that
      chlorhexidine would decelerate the loss of resin-dentin bonds. Class I
      preparations in extracted third molars were sectioned into two halves. One half
      was customarily restored (etch-and-rinse adhesive/resin composite), and the other
      was treated with 2% chlorhexidine after being acid-etched before restoration.
      Specimens were stored in artificial saliva with/without protease inhibitors.
      Microtensile bond strengths and failure mode distribution under SEM were analyzed
      immediately after specimens' preparation and 6 months later. With chlorhexidine,
      significantly better preservation of bond strength was observed after 6 months;
      protease inhibitors in the storage medium had no effect. Failure analysis showed
      significantly less failure in the hybrid layer with chlorhexidine, compared with
      controls after 6 months. In conclusion, this in vitro study suggests that
      chlorhexidine might be useful for the preservation of dentin bond strength.

PMID- 17189471
TI  - Efficacy of silver diamine fluoride for caries reduction in primary teeth and
      first permanent molars of schoolchildren: 36-month clinical trial.

PMID- 17189473
TI  - Mixed osmolytes: the degree to which one osmolyte affects the protein stabilizing
      ability of another.
AB  - Mixtures of organic osmolytes occur in cells of many organisms, raising the
      question of whether their actions on protein stability are independent or
      synergistic. To investigate this question it is desirable to develop a system
      that permits evaluation of the effect of one osmolyte on the efficacy of another
      to either force-fold or denature a protein. A means of evaluating the efficacy of
      an osmolyte is provided by its m-value, an experimental quantity that measures
      the ability of the osmolyte to force a protein to unfold or fold. An experimental
      system is presented that enables evaluations of the m-values of osmolytes in the
      presence and absence of a second osmolyte. The experimental system involves use
      of a marginally stable protein in 10 mM buffer (pH 7, 200 mM salt, and 34 degrees
      C) that is at the midpoint of its native to denatured transition. These
      conditions enable determination of m-values for protecting and denaturing
      osmolytes in the presence and absence of a second osmolyte, permitting assessment
      of the extent to which the two osmolytes affect each other's efficacy. The two
      osmolytes investigated in this work are the denaturing osmolyte, urea, and the
      protecting osmolyte, sarcosine. Results show unequivocally that neither osmolyte
      alters the efficacy of the other in forcing the protein to fold or unfold-the
      osmolytes act independently on the protein despite their combined concentrations
      being in the multi-molar range. These osmolytes avoid altering one another's
      efficacy at these high concentrations because the number of osmolyte interaction
      sites on the protein is large and the binding constants are quite small.
      Consequently, the site occupancies are low enough in number that the two
      osmolytes neither compete nor cooperate in interacting with the protein.

PMID- 17189472
TI  - Crystal structure of the BTB domain from the LRF/ZBTB7 transcriptional regulator.
AB  - BTB-zinc finger (BTB-ZF) proteins are transcription regulators with roles in
      development, differentiation, and oncogenesis. In these proteins, the BTB domain
      (also known as the POZ domain) is a protein-protein interaction motif that
      contains a dimerization interface, a possible oligomerization surface, and
      surfaces for interactions with other factors, including nuclear co-repressors and
      histone deacetylases. The BTB-ZF protein LRF (also known as ZBTB7, FBI-1, OCZF,
      and Pokemon) is a master regulator of oncogenesis, and represses the
      transcription of a variety of important genes, including the ARF, c-fos, and c
      myc oncogenes and extracellular matrix genes. We determined the crystal structure
      of the BTB domain from human LRF to 2.1 A and observed the canonical BTB
      homodimer fold. However, novel features are apparent on the surface of the
      homodimer, including differences in the lateral groove and charged pocket
      regions. The residues that line the lateral groove have little similarity with
      the equivalent residues from the BCL6 BTB domain, and we show that the 17-residue
      BCL6 Binding Domain (BBD) from the SMRT co-repressor does not bind to the LRF BTB
      domain.

PMID- 17189474
TI  - Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in
      vitro nucleic acid binding properties.
AB  - Rcd-1, a protein highly conserved across eukaryotes, was initially identified as
      a factor essential for nitrogen starvation-invoked differentiation in fission
      yeast, and its Saccharomyces cerevisiae homolog, CAF40, has been identified as
      part of the CCR4-NOT transcription complex, where it interacts with the NOT1
      protein. Mammalian homologs are involved in various cellular differentiation
      processes including retinoic acid-induced differentiation and hematopoetic cell
      development. Here, we present the 2.2 A X-ray structure of the highly conserved
      region of human Rcd-1 and investigate possible functional abilities of this and
      the full-length protein. The monomer is made up of six armadillo repeats forming
      a solvent-accessible, positively-charged cleft 21-22 A wide that, in contrast to
      other armadillo proteins, stays fully exposed in the dimer. Prompted by this
      finding, we established that Rcd-1 can bind to single- and double-stranded
      oligonucleotides in vitro with the affinity of G/C/T >> A. Mutation of an
      arginine residue within the cleft strongly reduced or abolished oligonucleotide
      binding. Rcd-1's ability to bind to nucleic acids, in addition to the previously
      reported protein-protein interaction with NOT1, suggests a new feature in Rcd-1's
      role in regulation of overall cellular differentiation processes.

PMID- 17189475
TI  - Self-assembly of coiled-coil tetramers in the 1.40 A structure of a leucine
      zipper mutant.
AB  - The hydrophobic core of the GCN4 leucine-zipper dimerization domain is formed by
      a parallel helical association between nonpolar side chains at the a and d
      positions of the heptad repeat. Here we report a self-assembling coiled-coil
      array formed by the GCN4-pAe peptide that differs from the wild-type GCN4 leucine
      zipper by alanine substitutions at three charged e positions. GCN4-pAe is
      incompletely folded in normal solution conditions yet self-assembles into an
      antiparallel tetraplex in crystals by formation of unanticipated hydrophobic
      seams linking the last two heptads of two parallel double-stranded coiled coils.
      The GCN4-pAe tetramers in the lattice associate laterally through the identical
      interactions to those in the intramolecular dimer-dimer interface. The van der
      Waals packing interaction in the solid state controls extended supramolecular
      assembly of the protein, providing an unusual atomic scale view of a
      mesostructure.

PMID- 17189476
TI  - Is glycine a surrogate for a D-amino acid in the collagen triple helix?
AB  - Collagen is the most abundant protein in animals. Every third residue in a
      collagen strand is a glycine with phi, psi = -70 degrees, 175 degrees. A recent
      computational study suggested that replacing these glycine residues with D
      alanine or D-serine would stabilize the collagen triple helix. This hypothesis is
      of substantial importance, as the glycine residues in collagen constitute nearly
      10% of the amino acid residues in humans. To test this hypothesis, we synthesized
      a series of collagen mimic peptides that contain one or more D-alanine or D
      serine residues replacing the canonical glycine residues. Circular dichroism
      spectroscopy and thermal denaturation experiments indicated clearly that the
      substitution of glycine with D-alanine or D-serine greatly disfavors the
      formation of a triple helix. Host-guest studies also revealed that replacing a
      single glycine residue with D-alanine is more destabilizing than is its
      replacement with L-alanine, a substitution that results from a common mutation in
      patients with collagen-related diseases. These data indicate that the glycine
      residues in collagen are not a surrogate for a D-amino acid and support the
      notion that the main-chain torsion angles of a glycine residue in the native
      structure (especially, phi > 0 degrees ) are critical determinants for its
      beneficial substitution with a D-amino acid in a protein.

PMID- 17189477
TI  - Redesigning protein pKa values.
AB  - The ability to re-engineer enzymatic pH-activity profiles is of importance for
      industrial applications of enzymes. We theoretically explore the feasibility of
      re-engineering enzymatic pH-activity profiles by changing active site pK(a)
      values using point mutations. We calculate the maximum achievable DeltapK(a)
      values for 141 target titratable groups in seven enzymes by introducing
      conservative net-charge altering point mutations. We examine the importance of
      the number of mutations introduced, their distance from the target titratable
      group, and the characteristics of the target group itself. The results show that
      multiple mutations at 10A can change pK(a) values up to two units, but that the
      introduction of a requirement to keep other pK(a) values constant reduces the
      magnitude of the achievable DeltapK(a). The algorithm presented shows a good
      correlation with existing experimental data and is available for download and via
      a web server at http://enzyme.ucd.ie/pKD.

PMID- 17189478
TI  - C-terminal loop of Streptomyces phospholipase D has multiple functional roles.
AB  - We have recently shown that two flexible loops of Streptomyces phospholipase D
      (PLD) affect the catalytic reaction of the enzyme by a comparative study of
      chimeric PLDs. Gly188 and Asp191 of PLD from Streptomyces septatus TH-2 (TH-2PLD)
      were identified as the key amino acid residues involved in the recognition of
      phospholipids. In the present study, we further investigated the relationship
      between a C-terminal loop of TH-2PLD and PLD activities to elucidate the reaction
      mechanism and the recognition of the substrate. By analyzing chimeras and mutants
      in terms of hydrolytic and transphosphatidylation activities, Ala426 and Lys438
      of TH-2PLD were identified as the residues associated with the activities. We
      found that Gly188 and Asp191 recognized substrate forms, whereas residues Ala426
      and Lys438 enhanced transphosphatidylation and hydrolysis activities regardless
      of the substrate form. By substituting Ala426 and Lys438 with Phe and His,
      respectively, the mutant showed not only higher activities but also higher
      thermostability and tolerance against organic solvents. Furthermore, the mutant
      also improved the selectivity of the transphosphatidylation activity. The
      residues Ala426 and Lys438 were located in the C-terminal flexible loop of
      Streptomyces PLD separate from the highly conserved catalytic HxKxxxxD motifs. We
      demonstrated that this C-terminal loop, which formed the entrance of the active
      well, has multiple functional roles in Streptomyces PLD.

PMID- 17189479
TI  - Evaluation of features for catalytic residue prediction in novel folds.
AB  - Structural genomics projects are determining the three-dimensional structure of
      proteins without full characterization of their function. A critical part of the
      annotation process involves appropriate knowledge representation and prediction
      of functionally important residue environments. We have developed a method to
      extract features from sequence, sequence alignments, three-dimensional structure,
      and structural environment conservation, and used support vector machines to
      annotate homologous and nonhomologous residue positions based on a specific
      training set of residue functions. In order to evaluate this pipeline for
      automated protein annotation, we applied it to the challenging problem of
      prediction of catalytic residues in enzymes. We also ranked the features based on
      their ability to discriminate catalytic from noncatalytic residues. When applying
      our method to a well-annotated set of protein structures, we found that top
      ranked features were a measure of sequence conservation, a measure of structural
      conservation, a degree of uniqueness of a residue's structural environment,
      solvent accessibility, and residue hydrophobicity. We also found that features
      based on structural conservation were complementary to those based on sequence
      conservation and that they were capable of increasing predictor performance.
      Using a family nonredundant version of the ASTRAL 40 v1.65 data set, we estimated
      that the true catalytic residues were correctly predicted in 57.0% of the cases,
      with a precision of 18.5%. When testing on proteins containing novel folds not
      used in training, the best features were highly correlated with the training on
      families, thus validating the approach to nonhomologous catalytic residue
      prediction in general. We then applied the method to 2781 coordinate files from
      the structural genomics target pipeline and identified both highly ranked and
      highly clustered groups of predicted catalytic residues.

PMID- 17189480
TI  - The SH3 domain of a M7 interacts with its C-terminal proline-rich region.
AB  - Myosins play essential roles in migration, cytokinesis, endocytosis, and
      adhesion. They are composed of a large N-terminal motor domain with ATPase and
      actin binding sites and C-terminal neck and tail regions, whose functional roles
      and structural context in the protein are less well characterized. The tail
      regions of myosins I, IV, VII, XII, and XV each contain a putative SH3 domain
      that may be involved in protein-protein interactions. SH3 domains are reported to
      bind proline-rich motifs, especially "PxxP" sequences, and such interactions
      serve regulatory functions. The activity of Src, PI3, and Itk kinases, for
      example, is regulated by intramolecular interactions between their SH3 domain and
      internal proline-rich sequences. Here, we use NMR spectroscopy to reveal the
      structure of a protein construct from Dictyostelium myosin VII (DdM7) spanning
      A1620-T1706, which contains its SH3 domain and adjacent proline-rich region. The
      SH3 domain forms the signature beta-barrel architecture found in other SH3
      domains, with conserved tryptophan and tyrosine residues forming a hydrophobic
      pocket known to bind "PxxP" motifs. In addition, acidic residues in the RT or n
      Src loops are available to interact with the basic anchoring residues that are
      typically found in ligands or proteins that bind SH3 domains. The DdM7 SH3
      differs in the hydrophobicity of the second pocket formed by the 3(10) helix and
      following beta-strand, which contains polar rather than hydrophobic side chains.
      Most unusual, however, is that this domain binds its adjacent proline-rich region
      at a surface remote from the region previously identified to bind "PxxP" motifs.
      The interaction may affect the orientation of the tail without sacrificing the
      availability of the canonical "PxxP"-binding surface.

PMID- 17189481
TI  - The transmembrane homotrimer of ADAM 1 in model lipid bilayers.
AB  - Fertilin is a transmembrane protein heterodimer formed by the two subunits
      fertilin alpha and fertilin beta that plays an important role in sperm-egg
      fusion. Fertilin alpha and beta are members of the ADAM family, and contain each
      one transmembrane alpha-helix, and are termed ADAM 1 and ADAM 2, respectively.
      ADAM 1 is the subunit that contains a putative fusion peptide, and we have
      explored the possibility that the transmembrane alpha-helical domain of ADAM 1
      forms homotrimers, in common with other viral fusion proteins. Although this
      peptide was found to form various homooligomers in SDS, the infrared dichroic
      data obtained with the isotopically labeled peptide at specific positions is
      consistent with the presence of only one species in DMPC or POPC lipid bilayers.
      Comparison of the experimental orientational data with molecular dynamics
      simulations performed with sequence homologues of ADAM 1 show that the species
      present in lipid bilayers is only consistent with an evolutionarily conserved
      homotrimeric model for which we provide a backbone structure. These results
      support a model where ADAM 1 forms homotrimers as a step to create a fusion
      active intermediate.

PMID- 17189483
TI  - Prediction of structures of multidomain proteins from structures of the
      individual domains.
AB  - We describe the development of a method for assembling structures of multidomain
      proteins from structures of isolated domains. The method consists of an initial
      low-resolution search in which the conformational space of the domain linker is
      explored using the Rosetta de novo structure prediction method, followed by a
      high-resolution search in which all atoms are treated explicitly and backbone and
      side chain degrees of freedom are simultaneously optimized. The method
      recapitulates, often with very high accuracy, the structures of existing
      multidomain proteins.

PMID- 17189482
TI  - Thermodynamic stability of a cold-adapted protein, type III antifreeze protein,
      and energetic contribution of salt bridges.
AB  - A thermodynamic analysis of a cold-adapted protein, type III anti-freeze protein
      (AFP), was carried out. The results indicate that the folding equilibrium of type
      III AFP is a reversible, unimolecular, two-state process with no populated
      intermediates. Compared to most mesophilic proteins whose folding is two-state,
      the psychrophilic type III AFP has a much lower thermodynamic stability at 25
      degrees C, approximately 3 kcal/mol, and presents a remarkably downshifted
      stability-temperature curve, reaching a maximum of 5 kcal/mol around 0 degrees C.
      Type III AFPs contain few and non-optimally distributed surface charges relative
      to their mesophilic homologs, the C-terminal domains of sialic acid synthases. We
      used thermodynamic double mutant cycles to evaluate the energetic role of every
      surface salt bridge in type III AFP. Two isolated salt bridges provided no
      contribution to stability, while the Asp36-Arg39 salt bridge, involved in a salt
      bridge network with the C-terminal carboxylate, had a substantial contribution
      (approximately 1 kcal/mol). However, this contribution was more than counteracted
      by the destabilizing effect of the Asp36 carboxylate itself, whose removal led to
      a net 30% increase in stability at 25 degrees C. This study suggests that type
      III AFPs may have evolved for a minimally acceptable stability at the restricted,
      low temperature range (around 0 degrees C) at which AFPs must function. In
      addition, it indicates that salt bridge networks are used in nature also for the
      stability of psychrophilic proteins, and has led to a type III AFP variant of
      increased stability that could be used for biotechnological purposes.

PMID- 17189484
TI  - Role of Cdc42-Cla4 interaction in the pheromone response of Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae, the highly conserved Rho-type GTPase Cdc42 is
      essential for cell division and controls cellular development during mating and
      invasive growth. The role of Cdc42 in mating has been controversial, but a number
      of previous studies suggest that the GTPase controls the mitogen-activated
      protein (MAP) kinase cascade by activating the p21-activated protein kinase (PAK)
      Ste20. To further explore the role of Cdc42 in pheromone-stimulated signaling, we
      isolated novel alleles of CDC42 that confer resistance to pheromone. We find that
      in CDC42(V36A) and CDC42(V36A, I182T) mutant strains, the inability to undergo
      pheromone-induced cell cycle arrest correlates with reduced phosphorylation of
      the mating MAP kinases Fus3 and Kss1 and with a decrease in mating efficiency.
      Furthermore, Cdc42(V36A) and Cdc42(V36A, I182T) proteins show reduced interaction
      with the PAK Cla4 but not with Ste20. We also show that deletion of CLA4 in a
      CDC42(V36A, I182T) mutant strain suppresses pheromone resistance and that
      overexpression of CLA4 interferes with pheromone-induced cell cycle arrest and
      MAP kinase phosphorylation in CDC42 wild-type strains. Our data indicate that
      Cla4 has the potential to act as a negative regulator of the mating pathway and
      that this function of the PAK might be under control of Cdc42. In conclusion, our
      study suggests that control of pheromone signaling by Cdc42 not only depends on
      Ste20 but also involves interaction of the GTPase with Cla4.

PMID- 17189485
TI  - Comprehensive analysis of glycosylphosphatidylinositol-anchored proteins in
      Candida albicans.

PMID- 17189487
TI  - Novel phacB-encoded cytochrome P450 monooxygenase from Aspergillus nidulans with
      3-hydroxyphenylacetate 6-hydroxylase and 3,4-dihydroxyphenylacetate 6-hydroxylase
      activities.
AB  - Aspergillus nidulans catabolizes phenylacetate (PhAc) and 3-hydroxy-, 4-hydroxy-,
      and 3,4-dihydroxyphenylacetate (3-OH-PhAc, 4-OH-PhAc, and 3,4-diOH-PhAc,
      respectively) through the 2,5-dihydroxyphenylacetate (homogentisic acid)
      catabolic pathway. Using cDNA subtraction techniques, we isolated a gene, denoted
      phacB, which is strongly induced by PhAc (and its hydroxyderivatives) and encodes
      a new cytochrome P450 (CYP450). A disrupted phacB strain (delta phacB) does not
      grow on 3-hydroxy-, 4-hydroxy-, or 3,4-dihydroxy-PhAc. High-performance liquid
      chromatography and gas chromatography-mass spectrum analyses of in vitro
      reactions using microsomes from wild-type and several A. nidulans mutant strains
      confirmed that the phacB-encoded CYP450 catalyzes 3-hydroxyphenylacetate and 3,4
      dihydroxyphenylacetate 6-hydroxylations to generate 2,5-dihydroxyphenylacetate
      and 2,4,5-trihydroxyphenylacetate, respectively. Both of these compounds are used
      as substrates by homogentisate dioxygenase. This cytochrome P450 protein also
      uses PhAc as a substrate to generate 2-OH-PhAc with a very low efficiency. The
      phacB gene is the first member of a new CYP450 subfamily (CYP504B).

PMID- 17189486
TI  - GAS2 and GAS4, a pair of developmentally regulated genes required for spore wall
      assembly in Saccharomyces cerevisiae.
AB  - The GAS multigene family of Saccharomyces cerevisiae is composed of five paralogs
      (GAS1 to GAS5). GAS1 is the only one of these genes that has been characterized
      to date. It encodes a glycosylphosphatidylinositol-anchored protein functioning
      as a beta(1,3)-glucan elongase and required for proper cell wall assembly during
      vegetative growth. In this study, we characterize the roles of the GAS2 and GAS4
      genes. These genes are expressed exclusively during sporulation. Their mRNA
      levels showed a peak at 7 h from induction of sporulation and then decreased.
      Gas2 and Gas4 proteins were detected and reached maximum levels between 8 and 10
      h from induction of sporulation, a time roughly coincident with spore wall
      assembly. The double null gas2 gas4 diploid mutant showed a severe reduction in
      the efficiency of sporulation, an increased permeability of the spores to
      exogenous substances, and production of inviable spores, whereas the single gas2
      and gas4 null diploids were similar to the parental strain. An analysis of spore
      ultrastructure indicated that the loss of Gas2 and Gas4 proteins affected the
      proper attachment of the glucan to the chitosan layer, probably as a consequence
      of the lack of coherence of the glucan layer. The ectopic expression of GAS2 and
      GAS4 genes in a gas1 null mutant revealed that these proteins are redundant
      versions of Gas1p specialized to function in a compartment at a pH value close to
      neutral.

PMID- 17189488
TI  - Divergence of protein kinase A catalytic subunits in Cryptococcus neoformans and
      Cryptococcus gattii illustrates evolutionary reconfiguration of a signaling
      cascade.
AB  - Gene duplication and divergence via both the loss and gain of gene activities are
      powerful evolutionary forces underlying the origin of new biological functions.
      Here a comparative genetics approach was applied to examine the roles of protein
      kinase A (PKA) catalytic subunits in three closely related varieties or sibling
      species of the pathogenic fungus genus Cryptococcus. Previous studies revealed
      that two PKA catalytic subunits, Pka1 and Pka2, control virulence factor
      production and mating. However, only one of the two plays the predominant
      physiological role, and this function has been exchanged between Pka1 and Pka2 in
      strains of the Cryptococcus neoformans var. grubii serotype A lineage compared to
      divergent C. neoformans var. neoformans serotype D isolates. To understand the
      basis for this functional plasticity, here the activities of Pka1 and Pka2 were
      defined in the two varieties and the related sibling species Cryptococcus gattii
      by gene disruption and characterization, heterologous complementation, and
      analysis of serotype AD hybrid mutant strains. The findings provide evidence for
      a shared ancestral role of PKA in governing mating and virulence factor
      production and indicate that the exchange of catalytic subunit roles is
      attributable to loss of function. Our studies illustrate the plasticity of
      signaling networks enabling rapid rewiring during speciation of a clade of common
      human fungal pathogens.

PMID- 17189489
TI  - Saccharomyces cerevisiae multidrug resistance transporter Qdr2 is implicated in
      potassium uptake, providing a physiological advantage to quinidine-stressed
      cells.
AB  - The QDR2 gene of Saccharomyces cerevisiae encodes a putative plasma membrane
      drug:H(+) antiporter that confers resistance against quinidine, barban,
      bleomycin, and cisplatin. This work provides experimental evidence of defective
      K(+) (Rb(+)) uptake in the absence of QDR2. The direct involvement of Qdr2p in
      K(+) uptake is reinforced by the fact that increased K(+) (Rb(+)) uptake due to
      QDR2 expression is independent of the Trk1p/Trk2p system. QDR2 expression confers
      a physiological advantage for the yeast cell during the onset of K(+) limited
      growth, due either to a limiting level of K(+) in the growth medium or to the
      presence of quinidine. This drug decreases the K(+) uptake rate and K(+)
      accumulation in the yeast cell, especially in the Deltaqdr2 mutant. Qdr2p also
      helps to sustain the decrease of intracellular pH in quinidine-stressed cells in
      growth medium at pH 5.5 by indirectly promoting H(+) extrusion affected by the
      drug. The results are consistent with the hypothesis that Qdr2p may also couple
      K(+) movement with substrate export, presumably with quinidine. Other clues to
      the biological role of QDR2 in the yeast cell come from two additional lines of
      experimental evidence. First, QDR2 transcription is activated under nitrogen
      (NH(4)(+)) limitation or when the auxotrophic strain examined enters stationary
      phase due to leucine limitation, this regulation being dependent on general amino
      acid control by Gcn4p. Second, the amino acid pool is higher in Deltaqdr2 cells
      than in wild-type cells, indicating that QDR2 expression is, directly or
      indirectly, involved in amino acid homeostasis.

PMID- 17189490
TI  - Endoplasmic reticulum retention signal-dependent glycylation of the Hsp70/Grp170
      related Pgp1p in Tetrahymena.
AB  - Glycylation is an uncommon posttranslational modification. It has been found that
      tubulin glycylation is essential for cell survival in Tetrahymena. Here we
      describe PGP1, a Tetrahymena gene encoding an Hsp70 homologue that is a novel
      glycylated protein. Pgp1p is a conserved glycoprotein that localizes within the
      lumen of the endoplasmic reticulum (ER). We demonstrate that PGP1 is essential
      for viability and present evidence that both glycosylation and ER retention are
      necessary but not sufficient for glycylation.

PMID- 17189493
TI  - Violence and exploitation against women and girls. Proceedings of a Psychology
      Section meeting at the New York Academy of Sciences. November 18, 2005. New York,
      New York, USA.

PMID- 17189491
TI  - Genome-wide analysis of C/D and H/ACA-like small nucleolar RNAs in Leishmania
      major indicates conservation among trypanosomatids in the repertoire and in their
      rRNA targets.
AB  - Small nucleolar RNAs (snoRNAs) are a large group of noncoding RNAs that exist in
      eukaryotes and archaea and guide modifications such as 2'-O-ribose methylations
      and pseudouridylation on rRNAs and snRNAs. Recently, we described a genome-wide
      screening approach with Trypanosoma brucei that revealed over 90 guide RNAs. In
      this study, we extended this approach to analyze the repertoire of the closely
      related human pathogen Leishmania major. We describe 23 clusters that encode 62
      C/Ds that can potentially guide 79 methylations and 37 H/ACA-like RNAs that can
      potentially guide 30 pseudouridylation reactions. Like T. brucei, Leishmania also
      contains many modifications and guide RNAs relative to its genome size. This
      study describes 10 H/ACAs and 14 C/Ds that were not found in T. brucei. Mapping
      of 2'-O-methylations in rRNA regions rich in modifications suggests the existence
      of trypanosomatid-specific modifications conserved in T. brucei and Leishmania.
      Structural features of C/D snoRNAs, such as copy number, conservation of boxes, K
      turns, and intragenic and extragenic base pairing, were examined to elucidate the
      great variation in snoRNA abundance. This study highlights the power of
      comparative genomics for determining conserved features of noncoding RNAs.

PMID- 17189494
TI  - Perspectives on violence.
AB  - The worldwide rise in violence, especially that directed against females of all
      ages, led the World Health Organization (WHO) to undertake steps to deal with
      that problem. To do so, WHO adopted a public health approach. This entailed (1)
      developing a definition of violence, (2) devising a typology of violent acts, (3)
      creating a uniform database for reporting violence, and (4) promulgating a model
      for understanding violence and its attendant phenomena. This essay reviews,
      analyzes, and critiques those efforts.

PMID- 17189495
TI  - A protoscientific master metaphor for framing violence.
AB  - Every new field of investigation requires a guiding scheme or frame. Its purpose
      is to provide a heuristic for discovery and a structure for organizing
      information. Neither the World Health Organization's public health nor a
      biosocial model of violence are adequate for providing a protoscientific frame
      for conceptualizing violent acts. This essay suggests a master metaphor--Burke's
      Dramatism--through which to deepen and expand our knowledge of violence and what
      must be done to reduce its toll. An illustrative example is presented.

PMID- 17189492
TI  - BcSAK1, a stress-activated mitogen-activated protein kinase, is involved in
      vegetative differentiation and pathogenicity in Botrytis cinerea.
AB  - The gene bcsak1, encoding a mitogen-activated protein kinase (MAPK) of Botrytis
      cinerea, was cloned and characterized. The protein has high homology to the yeast
      Hog1 and to corresponding MAPKs from filamentous fungi, but it shows unique
      functional features. The protein is phosphorylated under osmotic stress, specific
      fungicides, and oxidative stress mediated by H(2)O(2) and menadione. Northern
      blot analyses indicate that only a subset of typical oxidative stress response
      genes is regulated by BcSAK1. In contrast to most other fungal systems,
      Deltabcsak1 mutants are significantly impaired in vegetative and pathogenic
      development: they are blocked in conidia formation, show increased sclerotial
      development, and are unable to penetrate unwounded plant tissue. These data
      indicate that in B. cinerea the stress-activated MAPK cascade is involved in
      essential differentiation programs.

PMID- 17189496
TI  - Sexual aggression toward women: reducing the prevalence.
AB  - Date rape or acquaintance rape is far more common than rape by strangers and can
      lead to serious health and adjustment problems for girls and women. Research has
      found women and men to be similar in many of their views about sexual assault.
      However, studies on attribution of blame have highlighted differences in the ways
      in which men and women attribute blame in sexual assault. Men attribute less
      blame to perpetrators of sexual assault than do women, regardless of whether the
      perpetrator is female or male. This suggests that men identify with the power
      associated with the role of perpetrator. Ways of reducing the prevalence of men's
      sexual aggressiveness toward women are addressed.

PMID- 17189497
TI  - Adolescent girls speak about violence in their community.
AB  - Adolescent girls growing up in urban environments have been placed at increased
      risk for being exposed to violence in their communities. Yet few studies have
      examined their perceptions of the risk factors, violence, and the pressures they
      face on a daily basis. The present research describes two adolescent girls'
      perspectives concerning the challenges, fears, hopes, risks, and pressures they
      have experienced growing up in their community. The results have implications for
      violence intervention and prevention programs with adolescent girls living in
      urban environments.

PMID- 17189498
TI  - Who wins in the status games? Violence, sexual violence, and an emerging single
      standard among adolescent women.
AB  - Throughout U.S. history, women have changed their sexual behaviors in response
      to, or as actors affecting, economic, political, and legal imperatives; to
      preserve health; to promote new relationship, identity or career paths; to assert
      a set of values; as a result of new reproductive technologies; or to gain status.
      In adjusting to pressures or goals, women have not always acted, or been able to
      act, in the interests of their own health, identity, or status. As this article
      will demonstrate, women, in the short or long run, may attempt to preserve status
      at the cost of other values such as health. This may occur through conscious and
      critical choice or through less conscious processes in reaction to relatively
      larger forces whose impact has not been critically analyzed. With the awareness
      in the 1980s in the United States of an emergent and incurable sexually
      transmissible infection, HIV, it would have been anticipated that a new sexual
      caution may have appeared. Yet, across several research projects in the late
      1990s and into the 21st century, as our research team interviewed youth in a high
      HIV seroprevalence neighborhood in New York City about HIV prevention, we began
      to hear that a substantial minority of young women and men were participating in
      social settings for sexual behavior that (1) put youth at risk for HIV; (2)
      appeared to be motivated by acquisition of status ("props," "points"); and (3)
      offered few ways for women to win in these status games. We estimate from one
      random dwelling unit sample that about one in eight youth have been present in
      these settings and half of them have participated in risky sexual behavior in
      such settings. The settings are often characterized by men's publicly offhand
      attitudes toward sexual encounters, are organized around men's status
      maintenance, and evidence peer pressures that are poorly understood by both young
      men and women participants. To regain status, some women participants have
      adopted attitudes more characteristic of men.

PMID- 17189499
TI  - Cyberspace violence against girls and adolescent females.
AB  - Children and adolescents today are the first generation raised in a society in
      which technological literacy is essential for effective citizenship in the 21st
      century. With many more youth using digital technologies for educational and
      recreational purposes, there has been an increase in social problems in
      cyberspace, exposing them to different forms of cyberviolence. This article gives
      an overview of the developments in cyberspace, describes different types of
      cyberviolence, and focuses on cyberbullying among girls and adolescent females as
      both victims and perpetrators of cyberbullying. At-risk online activities among
      girls and adolescent females as well as strategies to promote cybersafety are
      presented. Current research and future directions for research are reviewed.

PMID- 17189500
TI  - Early violence prevention programs: implications for violence prevention against
      girls and women.
AB  - This chapter considers violence prevention programs in light of aggression and
      violence directed toward girls and women. More specifically, current violence
      prevention programs, directed toward young children and/or their caregivers, are
      discussed with a special consideration for the Adults and Children Together (ACT)
      Against Violence Training Program developed by the American Psychological
      Association (APA) and the National Association of Education of Young Children
      (NAEYC). Data supporting ACT is presented, with implications for further program
      development and evaluation. Finally, parent education, theory and research, and
      professional services related to violence prevention are discussed.

PMID- 17189501
TI  - International perspectives on sexual harassment of college students: the sounds
      of silence.
AB  - The incidence, psychological dimensions, reporting, and impact of sexual
      harassment of college students throughout the world are reviewed. Special
      attention is paid to methodological constraints in conducting cross-cultural
      research in sexual harassment, including difficulty in securing research
      participants, different methodologies to collect incidence data, use of
      retrospective data, and varying, definitions of sexual harassment.
      Recommendations for implementing intervention programs are offered. The
      strategies suggested deal with the social causes that maintain the harassment,
      including renegotiating the balance of power between men and women.

PMID- 17189502
TI  - Intimate partner violence: new directions.
AB  - This review examines multiple forms of intimate partner violence, including
      women's use of violence, and argues for development of more complex
      conceptualizations of intimate partner violence. As new victims are identified,
      partner violence has been reconceptualized. Research findings indicate that women
      are both victims and perpetrators in intimate partner violence, challenging
      previous conceptualizations and explanations. The authors argue that how
      researchers conceptualize intimate partner violence influences how they study and
      measure it. The authors call for researchers to develop more complex
      constructions of gender, and to distinguish between distinct forms of intimate
      partner violence.

PMID- 17189503
TI  - Battered woman syndrome: empirical findings.
AB  - The construct of Battered Woman Syndrome (BWS) has been conceptualized as a
      subcategory of posttraumatic stress disorder (PTSD). It is composed of the
      following symptoms: (a) re-experiencing the battering as if it were reoccurring
      even when it is not, (b) attempts to avoid the psychological impact of battering
      by avoiding activities, people, and emotions, (c) hyperarousal or hypervigilance,
      (d) disrupted interpersonal relationships, (e) body image distortion or other
      somatic concerns, and (f) sexuality and intimacy issues. This article presents
      empirical data derived from administering the Battered Woman Syndrome
      Questionnaire (BWSQ) to women of four countries--United States, Spain, Greece,
      and Russia. The data support a theory of BWS.

PMID- 17189504
TI  - Factors that influence abusive interactions between aging women and their
      caregivers.
AB  - Research findings suggest that one or more factors-personality and/or drug or
      financial dependency, cognitive and personality impairments, contextual factors,
      or severe stress-render elders vulnerable to caregiver maltreatment (i.e., either
      abuse or neglect), but may also make them more prone to abusing their caregivers.
      However, it is often the interaction between elders and caregivers that
      determines whether maltreatment will actually occur. Maltreatment of elders is
      less likely when caregivers (1) are free of mental impairments and of drug and
      personality dependency, (2) are trained to cope with the stress of caregiving and
      of highly provocative and/or abusive elders, (3) and are adequately reimbursed
      and socially supported.

PMID- 17189506
TI  - Gender-based violence: concepts, methods, and findings.
AB  - The United Nations has identified gender-based violence against women as a global
      health and development issue, and a host of policies, public education, and
      action programs aimed at reducing gender-based violence have been undertaken
      around the world. This article highlights new conceptualizations, methodological
      issues, and selected research findings that can inform such activities. In
      addition to describing recent research findings that document relationships
      between gender, power, sexuality, and intimate violence cross-nationally, it
      identifies cultural factors, including linkages between sex and violence through
      media images that may increase women's risk for violence, and profiles a host of
      negative physical, mental, and behavioral health outcomes associated with
      victimization including unwanted pregnancy and abortion. More research is needed
      to identify the causes, dynamics, and outcomes of gender-based violence,
      including media effects, and to articulate how different forms of such violence
      vary in outcomes depending on cultural context.

PMID- 17189505
TI  - Violence and exploitation against women and girls with disability.
AB  - This article seeks to explore issues concerning women and girls with disability
      who have experienced violence and exploitation. Owing to different methodologies
      of data collection, it is difficult to precisely determine the exact number of
      women and girls who are affected. The literature suggests that violence and
      exploitation against women and girls with disability occur at a rate 50% higher
      than in the rest of society. It also points out a number of additional critical
      issues: professionals are uneducated nd insensitive to the needs of these
      populations; increasing numbers of women and girls living with disability
      exacerbate the problem; women and girls with disability are uneducated about
      their rights and responsibilities; and action must be taken to halt this
      epidemic.

PMID- 17189507
TI  - Restoring rape survivors: justice, advocacy, and a call to action.
AB  - Rape results in mental and physical health, social, and legal consequences. For
      the latter, restorative justice-based programs might augment community response,
      but they generate controversy among advocates and policy makers. This article
      identifies survivors' needs and existing community responses to them. Survivors
      feel their legal needs are most poorly met due to justice system problems that
      can be summarized as attrition, retraumatization, and disparate treatment across
      gender, class, and ethnic lines. Empirical data support each problem and the
      conclusion that present justice options are inadequate. The article concludes by
      identifying common ground in advocacy and restorative justice goals and calls for
      a holistic approach to the needs of rape survivors that includes advocating for
      expanded justice alternatives. A call to action is issued to implement
      restorative alternatives to expand survivor choice and offender accountability.
      Conventional and restorative justice are often viewed as mutually exclusive
      whereas the author argues they are complementary.

PMID- 17189509
TI  - Cultural beliefs and domestic violence.
AB  - The role of cultural beliefs in domestic violence is examined within the context
      of the identification of more culturally viable options for women who are
      operating within diverse cultural frameworks and experiencing domestic violence
      worldwide. Domestic violence advocacy efforts are encouraged to incorporate more
      culturally informed strategies that complement the worldviews and cultural
      traditions of women from different backgrounds. The need for a more culturally
      sensitive definition of domestic violence that is inclusive of a range of
      domestic violence across cultures and also enhances communication among victims
      is identified. Points of relevant cultural reference are discussed and a cultural
      cost-benefit analysis is recommended for culturally relevant domestic violence
      research and program implementation.

PMID- 17189508
TI  - Violence against women as a public health issue.
AB  - Violence can be considered "infectious" in rape-prone cultures that celebrate
      violence and domination. The number of annual injuries and deaths due to violence
      against women and girls is high enough to demand the type of active interventions
      and public policies that have been targeted at infectious diseases by public
      health agencies. In this article, we review data on the physical and mental
      health effects that violence has on victims of domestic violence, rape, stalking,
      and sexual harassment. We also focus on the economic costs to the health care
      system, business and industry, families, and the broader society that accrue as a
      result of the widespread violence against women and girls. Victims' suffering can
      never be accounted for by economic data, but those data may be helpful in pushing
      governments to allocate funds and agencies to take preventive actions.

PMID- 17189510
TI  - Violence against women in Mexico: conceptualization and program application.
AB  - Violence against women has been a problem in human cultures for centuries. This
      is still the case both in developed and in developing countries, but it is in
      developing countries where the problem is aggravated as the result of cultural
      norms that are tolerant of men exerting power over women and girls as a commonly
      accepted practice. This power is often put into practice through physical and
      psychological acts of violence. In Mexico, as in many other countries, there is a
      legal framework that protects women from such acts, yet in the case of Mexico it
      has not yet been translated into actual improvements in their lives. We present
      an overview of advances in legal remedies regarding violence towards females
      internationally and in Mexico. The fact that these advances per se do not lead to
      changes in social norms that tolerate violence against females is emphasized.
      Also presented is the experience of the Mexican Institute for Research on Family
      and Population (IMIFAP) with the design and implementation of programs that
      promote protective factors and changes in behaviors in such a way that violence
      is effectively prevented. These programs focus on the development of psychosocial
      skills and knowledge through participatory workshops that promote self
      reflection, and they are developed and evaluated before being then applied on a
      large scale in poverty-stricken communities. These workshops lead to more
      egalitarian relationships between genders. IMIFAP's programs address not only
      violence but also other areas are integrated such that the enablement of
      psychosocial skills is applied in the broader socio-cultural context, leading to
      healthier and economically more productive lives. These programs are derived from
      the Framework for Enabling Agentic Empowerment (FENAE), which enables choice and
      the development of agentic empowerment through integrating skills, knowledge, and
      the context in which people live.

PMID- 17189511
TI  - Domestic violence in the Chinese and South Asian immigrant communities.
AB  - Although the Chinese and South Asian immigrant populations are largely silent on
      this issue, domestic violence is a fact of life in many families. In this
      article, we discuss cultural factors that may cause and prolong abuse in Asian
      immigrant homes, and review similarities and differences between the two Asian
      cultures in this regard. This article also addresses the psychological trauma
      experienced by abused Asian immigrant women and the coping strategies that they
      are likely to employ. Culturally sensitive intervention strategies are presented
      that may be appropriately used in working with Chinese and South Asian immigrant
      women for whom abuse is a terrifying and demeaning fact of life.

PMID- 17189512
TI  - Domestic violence in Israel: changing attitudes.
AB  - For many years, knowledge of the prevalence of violence against women in Israel
      was marginalized in such a way that it never figured in public discourse. Elite
      groups of academics and feminist activists with a Western background, together
      with human rights groups, delivered subversive messages that gradually
      infiltrated into larger circles and ultimately changed public policies. The issue
      is now central in public affairs. This article discusses the extent of violence
      against women in Israel and suggests explanations for the shift from denial to
      greater public awareness.

PMID- 17189514
TI  - Violence against pregnant women in Northwestern Ontario.
AB  - Violence against women during pregnancy is a global problem with adverse outcomes
      for the mothers and their children. This paper provides a discussion of the
      prevalence rates of pregnancy-related violence, associated factors, and outcomes.
      Most of the outcome literature focuses on perinatal and postnatal outcomes, but
      little is known about the longer term psychological outcome of children born to
      women abused during pregnancy. Moreover, the question as to whether the abuse
      increases during pregnancy remains unanswered given the equivocal findings in the
      literature. Findings from a small study conducted with women in the region of
      northwestern Ontario, Canada, are presented. The pattern of abuse during
      pregnancy over the three trimesters was examined. The long-term psychological
      outcomes of the children born to women abused during pregnancy were also
      investigated by comparing these children to a sex- and age-matched cohort of
      children born to women who were not abused during pregnancy. Although key
      confounding variables were controlled in the study, the results still showed that
      children born to women abused during pregnancy had greater behavioral problems.

PMID- 17189513
TI  - Lack of mutual respect in relationship: the endangered partner.
AB  - Violence in a relationship and in a family setting has been an issue of concern
      to various interest groups and professional organizations. Of particular interest
      in this article is violence against women in a relationship. While there is an
      abundance of knowledge on violence against women in general, intimate or partner
      femicide seems to have received less attention. Unfortunately, the incidence of
      violence against women, and intimate femicide in particular, has been an issue of
      concern in the African setting. This article examines the trends of intimate
      femicide in an African setting in general, and in Botswana in particular. The
      increase in intimate femicide is an issue of concern, which calls for collective
      effort to address. This article also examines trends of femicide in Botswana, and
      the antecedents and the precipitating factors. Some studies have implicated
      societal and cultural dynamics as playing significant roles in intimate femicide
      in the African setting. It is believed that the patriarchal nature of most
      African settings and the ideology of male supremacy have relegated women to a
      subordinate role. Consequently, respect for women in any relationship with men is
      lopsided in favor of men and has led to abuse of women, including intimate
      femicide. Other militating factors in intimate femicide are examined and the
      implications for counseling to assist the endangered female partner are
      discussed.

PMID- 17189515
TI  - An exploration of female genital mutilation.
AB  - Female genital mutilation (FGM) is a form of violence against women that has
      recently been labeled a public health issue. This article will define and
      describe the procedure as well as discuss its physical and psychological
      implications. An exploration of the cultural significance of the practice will
      shed light on its continued existence in underdeveloped and developed nations. In
      addition, an examination of suggested guidelines for creating and implementing
      effective interventions will ensue.

PMID- 17189516
TI  - International sexual harassment.
AB  - This paper on international sexual harassment begins with a presentation of the
      definitions, models, and consequences of sexual harassment. Following this
      discussion, a description is given of a nine-country research program that
      examined reactions to academic sexual harassment. A brief review of incidence
      studies and international laws related to sexual harassment are also included.

PMID- 17189517
TI  - United Nations measures to stop violence against women.
AB  - This article consists of a brief overview of the involvement by the United
      Nations (UN) and nongovernmental organizations (NGOs) in worldwide efforts to
      expose and prevent violence against women. It begins with a depiction of the
      types of gender-based violence in contemporary society. Then follows a short
      history of the institutions and mechanisms created by the UN and civil society to
      prevent domestic and public violence against women. It concludes with a sketch of
      ongoing UN/NGO efforts to build on the momentum of the last decade, and suggests
      the challenges this presents to each and all of us in the new millennium.

PMID- 17189520
TI  - Hypoxia-inducible factors in the first trimester human lung.
AB  - Lung development takes place in a relatively low-oxygen environment, which is
      beneficial for lung organogenesis, including vascular development. Hypoxia
      inducible factor (HIF)-1 plays an important role in mediating oxygen-regulated
      events. HIF-1 is stable and initiates gene transcription under hypoxia, whereas
      in normoxia, interaction with the von Hippel-Lindau (VHL) tumor suppressor
      protein leads to rapid degradation of the HIF-1alpha subunit. Interaction with
      VHL requires hydroxylation of HIF-1alpha proline residues by prolyl hydroxylases
      (PHDs). We investigated the expression of the various components regulating HIF
      1alpha stability in first trimester (8-14 weeks) human lungs. Spatial expression
      was assessed by immunohistochemistry and temporal expression by quantitative PCR.
      Immunoreactivity for PHD1, PHD3, and seven in absentia homolog (SIAH)1 was noted
      in the pulmonary epithelium. PHD2 was not expressed in the airway epithelium, but
      in the lung parenchyma. HIF-1alpha and vascular endothelial growth factor (VEGF)
      immunoreactivity were primarily detected in the branching epithelium. HIF-2alpha
      and ARNT proteins localized to the developing epithelium as well as mesenchymal,
      most likely vascular, structures in the parenchyma. VEGF receptor 2 (VEGFR2) was
      found in the subepithelium as well as in vascular structures of the mesenchyme.
      All components of the VEC complex (VHL, NEDD8, and Cullin2) were found in the
      epithelium. Quantitative PCR analysis demonstrated that VEGF, VEGFR1, HIF-1alpha,
      HIF-2alpha, ARNT, PHD1, PHD2, PHD3, and SIAH1 gene expression was constant during
      early pulmonary organogenesis. Cumulatively, the data suggest that the lung
      develops in a low-oxygen environment that allows for proper vascular development
      through HIF-regulated pathways.

PMID- 17189521
TI  - Expression of alpha 7 nicotinic acetylcholine receptors by bipolar, amacrine, and
      ganglion cells of the rabbit retina.
AB  - Cholinergic agents affect the light responses of many ganglion cells (GCs) in the
      mammalian retina by activating nicotinic acetylcholine receptors (nAChRs).
      Whereas retinal neurons that express beta2 subunit-containing nAChRs have been
      characterized in the rabbit retina, expression patterns of other nAChR subtypes
      remain unclear. Therefore, we evaluated the expression of alpha7 nAChRs in
      retinal neurons by means of single-, double-, and triple-label
      immunohistochemistry. Our data demonstrate that, in the rabbit retina, several
      types of bipolar cells, amacrine cells, and cells in the GC layer express alpha7
      nAChRs. At least three different populations of cone bipolar cells exhibited
      alpha7 labeling, whereas glycine-immunoreactive amacrine cells comprised the
      majority of alpha7-positive amacrine cells. Some GABAergic amacrine cells also
      displayed alpha7 immunoreactivity; alpha7 labeling was never detected in rod
      bipolar cells or rod amacrine cells (AII amacrine cells). Our data suggest that
      activation of alpha7 nAChRs by acetylcholine (ACh) or choline may affect
      glutamate release from several types of cone bipolar cells, modulating GC
      responses. ACh-induced excitation of inhibitory amacrine cells might cause either
      inhibition or disinhibition of other amacrine and GC circuits. Finally, ACh may
      act on alpha7 nAChRs expressed by GCs themselves.

PMID- 17189522
TI  - Osteopontin upregulation and polymerization by transglutaminase 2 in calcified
      arteries of Matrix Gla protein-deficient mice.
AB  - Matrix Gla protein (MGP) is a potent inhibitor of soft tissue calcification, and
      Mgp gene deletion in mice results in arterial calcification. Our aim was to
      examine osteopontin (OPN) expression and localization, and posttranslational
      processing of OPN by the crosslinking enzyme transglutaminase 2 (TG2), in the
      calcified aorta of Mgp-deficient (Mgp(-/-)) mice. Using immunohistochemistry and
      light and electron microscopy, we report that following mineralization occurring
      in the arterial media of Mgp(-/-) aortas, OPN is upregulated and accumulates at
      the surface of the calcified elastic lamellae. Macrophages were observed in
      direct contact with this OPN-rich layer. Western blot analysis of extracted Mgp(
      /-) aortas revealed that the majority of the OPN was in high molecular mass
      protein complexes, indicating modification by a crosslinking enzyme. Consistent
      with this observation, TG2 expression and gamma-glutamyl-epsilon-lysyl crosslink
      levels were also increased in Mgp(-/-) aortas. In addition to the mineral
      inhibiting actions of OPN, and based on data linking OPN and TG2 with cell
      adhesion in various cell types including monocytes and macrophages, we propose
      that TG2 interactions with OPN lead to protein polymerization that facilitates
      macrophage adhesion to the calcified elastic lamellae to promote clearance of the
      ectopic mineral deposits.

PMID- 17189523
TI  - Expression of Smad ubiquitin regulatory factor 2 (Smurf2) in rhesus monkey
      endometrium and placenta during early pregnancy.
AB  - Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that is
      involved in the Smad-mediated TGF-beta signaling. TGF-beta has been shown to play
      an important role during normal embryo implantation, but whether Smurf2 is
      involved in this process has not been reported. This study was first conducted to
      investigate the expression of Smurf2 transcript and protein in different
      compartments of the rhesus monkey uteri and placenta during early pregnancy. The
      results showed that both the cloned partial sequence of Smurf2 gene and the
      corresponding amino acid residues shared 99% identity with those of human
      homologs. On day 12 (D12) of pregnancy, strong signals of Smurf2 mRNA were found
      in basalis glandular epithelium and luminal epithelium, and moderate expressions
      were detected in functionalis glandular epithelium. During early villi stage and
      villi placental stage, Smurf2 mRNAs were mainly localized in the placenta villi,
      trophoblastic column, trophoblastic shell, and basalis glandular epithelium.
      There appeared strong staining signals in the arterioles on D26 of pregnancy, but
      faint staining signals on D18 of pregnancy. No specific staining of Smurf2 mRNA
      was observed in stromal cells and myometrium. The expression pattern of Smurf2
      protein was generally similar to that of its mRNA. These results provide the
      first evidence that Smurf2 may play specific roles in glandular secretion,
      trophoblastic cell invasion, and placentation through mediating the expression of
      the related proteins of TGF-beta signaling pathway during early pregnancy.

PMID- 17189524
TI  - Increased expression of the collagen internalization receptor uPARAP/Endo180 in
      the stroma of head and neck cancer.
AB  - Local growth, invasion, and metastasis of malignancies of the head and neck
      involve extensive degradation and remodeling of the underlying, collagen-rich
      connective tissue. Urokinase plasminogen activator receptor-associated protein
      (uPARAP)/Endo180 is an endocytic receptor recently shown to play a critical role
      in the uptake and intracellular degradation of collagen by mesenchymal cells. As
      a step toward determining the putative function of uPARAP/Endo180 in head and
      neck cancer progression, we used immunohistochemistry to determine the expression
      of this collagen internalization receptor in 112 human squamous cell carcinomas
      and 19 normal or tumor-adjacent head and neck tissue samples from the tongue,
      gingiva, cheek, tonsils, palate, floor of mouth, larynx, maxillary sinus, upper
      jaw, nasopharynx/nasal cavity, and lymph nodes. Specificity of detection was
      verified by staining of serial sections with two different monoclonal antibodies
      against two non-overlapping epitopes on uPARAP/Endo180 and by the use of isotype
      matched non-immune antibodies. uPARAP/Endo180 expression was observed in stromal
      fibroblast-like, vimentin-positive cells. Furthermore, expression of the collagen
      internalization receptor was increased in tumor stroma compared with tumor
      adjacent connective tissue or normal submucosal connective tissue and was most
      prominent in poorly differentiated tumors. These data suggest that uPARAP/Endo180
      participates in the connective tissue destruction during head and neck squamous
      cell carcinoma progression by mediating cellular uptake and lysosomal degradation
      of collagen.

PMID- 17189525
TI  - Expression profiles of mouse Kell, XK, and XPLAC mRNA.
AB  - Kell and XK are related because in red cells they exist as a disulfide-bonded
      complex. Kell is an endothelin-3-converting enzyme, and XK is predicted to be a
      transporter. Absence of XK, which is accompanied by reduced Kell on red cells,
      results in acanthocytosis and late-onset forms of central nervous system and
      neuromuscular abnormalities that characterize the McLeod syndrome. In this study,
      expression of mouse XK, XPLAC, a homolog of XK, and Kell were compared by in situ
      hybridization histochemistry (ISHH) and RT-PCR. ISHH showed that Kell and XK are
      coexpressed in erythroid tissues. ISHH detected XK, but not Kell, mRNA in testis,
      but RT-PCR indicated that both Kell and XK are coexpressed. XK, but not Kell, was
      significantly expressed in brain, spinal cord, small intestine, heart, stomach,
      bladder, and kidney. ISHH did not detect XK in skeletal muscle but RT-PCR did. In
      brain, XK was predominantly expressed in neuronal rather than in supportive
      cells. By contrast, XPLAC was predominantly expressed in the thymus. Coexpression
      of Kell and XK in erythroid tissues and the different expressions in non
      erythroid tissues suggest that XK may have a complementary hematological function
      with Kell and a separate role in other tissues.

PMID- 17189526
TI  - Distribution and variable expression of secretory pathway protein reticulocalbin
      in normal human organs and non-neoplastic pathological conditions.
AB  - Reticulocalbin (RCN) is one member of the Ca(2+)-binding proteins in the
      secretory pathway and is localized in the endoplasmic reticulum. RCN may play a
      role in the normal behavior and life of cells, although its detailed role remains
      unknown. Overexpression of RCN may also play a role in tumorigenesis, tumor
      invasion, and drug resistance. The new antibody for human RCN is used in the
      distribution of RCN in normal human organs of fetuses and adults with or without
      inflammation. Immunohistochemical examination demonstrated a broad distribution
      of RCN in various organs of fetuses and adults, predominantly in the endocrine
      and exocrine organs. However, RCN expression was heterogeneous in each
      constituent cell of some organs. Among non-epithelial organs, vascular
      endothelial cells, testicular germ cells, neurons, and follicular dendritic cells
      showed strong staining. Plasma cells were the only RCN-positive cells among
      hematopoietic and lymphoid cells. In inflammatory conditions, RCN expression was
      enhanced in both epithelial and non-epithelial cells. Heterogeneous expression of
      RCN indicates that the amount of RCN needed for cell behavior and life may be
      variable, depending on each cell type and, therefore, RCN may be helpful in
      establishing the cell origin of neoplasms in some organs. However, further study
      is needed to establish the significance of RCN in tumorigenesis and in some
      peculiar features of neoplasms.

PMID- 17189527
TI  - Coeliac disease and risk of tuberculosis: A population-based cohort study.

PMID- 17189528
TI  - High-grade lesion: What does it tell us?

PMID- 17189530
TI  - Priorities for respiratory research in the UK.

PMID- 17189529
TI  - What is this thing called CFA?

PMID- 17189531
TI  - Inflammation of bronchial smooth muscle in allergic asthma.
AB  - BACKGROUND: Recent observations in asthma suggest that bronchial smooth muscle is
      infiltrated by inflammatory cells including mast cells. Such an infiltration may
      contribute to airway remodelling that is partly due to an increase in smooth
      muscle mass. Whether muscle increase is the result of smooth muscle cell
      hypertrophy remains controversial and has not been studied by ultrastructural
      analysis. A morphometric analysis of airway smooth muscle (ASM) was undertaken in
      asthmatic patients using electron microscopy to examine the interactions between
      ASM cells and inflammatory cells. METHODS: ASM specimens were obtained from 14
      asthmatic subjects and nine non-asthmatic controls undergoing fibreoptic
      endoscopy. Inflammatory cell counts were assessed by immunohistochemistry, and
      ultrastructural parameters were measured using electron microscopy in a blinded
      fashion on smooth muscle cells and inflammatory cells. RESULTS: ASM from
      asthmatic patients was infiltrated by an increased number of mast cells and
      lymphocytes. Smooth muscle cells and their basal lamina were thicker in asthmatic
      patients (9.5 (0.8) and 1.4 (0.2) microm) than in controls (6.7 (0.4) and 0.7
      (0.1) microm). In asthmatics the extracellular matrix was frequently organised in
      large amounts between ASM cells. Myofibroblasts within smooth muscle bundles were
      only observed in asthmatics, some of them displaying a close contact with ASM
      cells. CONCLUSION: In asthma, airway myositis is characterised by a direct
      interaction between ASM cells and mast cells and lymphocytes. Smooth muscle
      remodelling was present, including cell hypertrophy and abnormal extracellular
      matrix deposition moulding ASM cells.

PMID- 17189532
TI  - Association of inducible nitric oxide synthase with asthma severity, total serum
      immunoglobulin E and blood eosinophil levels.
AB  - BACKGROUND: Nitric oxide is released by immune, epithelial and endothelial cells,
      and plays an important part in the pathophysiology of asthma. OBJECTIVE: To
      investigate the association of inducible nitric oxide synthases (iNOS) gene
      repeat polymorphisms with asthma. METHODS: 230 families with asthma (842
      individuals) were recruited to identify and establish the genetic association of
      iNOS repeats with asthma and associated phenotypes. Serum nitric oxide levels in
      selected individuals were measured and correlated with specific genotypes.
      Multiple logistic regression analysis was performed to determine the effect of
      age and sex. RESULTS: A total of four repeats-a (CCTTT)n promoter repeat, a novel
      intron 2 (GT)n repeat (BV680047), an intron 4 (GT)n repeat (AFM311ZB1) and an
      intron 5 (CA)n repeat (D17S1878)-were identified and genotyped. A significant
      transmission distortion to the probands with asthma was seen for allele 3 of the
      AFM311ZB1 gene (p = 0.006). This allele was also found to be significantly
      associated with percentage blood eosinophils (p < 0.001) and asthma severity (p =
      0.04). Moreover, it was functionally correlated with high serum nitric oxide
      levels (p = 0.006). Similarly, the promoter repeat was found to be associated
      with serum total immunoglobulin (Ig)E (p = 0.028). Individuals carrying allele 4
      of this repeat have high serum IgE (p < 0.001) and nitric oxide levels (p =
      0.03). CONCLUSION: This is the first study to identify the repeat polymorphisms
      in the iNOS gene that are associated with severity of asthma and eosinophils. The
      functional relevance of the associated alleles with serum nitric oxide levels was
      also shown. Therefore, these results could be valuable in elucidating the role of
      nitric oxide in asthma pathogenesis.

PMID- 17189534
TI  - Disseminated Mycobacterium tuberculosis infection due to interferon gamma
      deficiency. Response to replacement therapy.
AB  - The case of a previously healthy HIV seronegative woman with disseminated
      Mycobacterium tuberculosis infection and markedly reduced interferon gamma
      production is reported here. Complete healing of her disseminated lesions was
      seen only after addition of subcutaneous interferon gamma to her tuberculosis
      treatment.

PMID- 17189533
TI  - 50 years of asthma: UK trends from 1955 to 2004.
AB  - Trends in asthma indicators from population surveys (prevalence) and routine
      statistics (primary care, prescriptions, hospital admissions and mortality) in
      the UK were reviewed from 1955 to 2004. The prevalence of asthma increased in
      children by 2 to 3-fold, but may have flattened or even fallen recently. Current
      trends in adult prevalence are flat. The prevalence of a life-time diagnosis of
      asthma increased in all age groups. The incidence of new asthma episodes
      presenting to general practitioners increased in all ages to a plateau in the mid
      1990s and has declined since. During the 1990s, the annual prevalence of new
      cases of asthma and of treated asthma in general practice showed no major change.
      Hospital admissions increased from the early 1960s, more so in children, until
      the late 1980s and have fallen since. Asthma mortality showed two waves, a
      shorter and more intense one in the mid 1960s and a longer and less intense one
      in the late 1970s and early 1980s. The relative roles of diagnostic transfer,
      coding changes, medical care and epidemiological factors are discussed.

PMID- 17189535
TI  - Secondary bronchiolitis obliterans organising pneumonia in a patient with
      carbamazepine-induced hypogammaglobulinemia.

PMID- 17189536
TI  - A visfatin promoter polymorphism is associated with low-grade inflammation and
      type 2 diabetes.
AB  - Visfatin (also known as pre-B cell colony-enhancing factor, or PBEF) is a pro
      inflammatory adipokine expressed predominantly in visceral fat. We investigated
      whether polymorphisms at the visfatin/PBEF locus influence the risk of type 2
      diabetes (T2D). Linkage disequilibrium analysis of 52 single nucleotide
      polymorphisms spanning the entire gene (34.7 kb) plus 20.5 kb of the upstream
      region and 25.5 kb of the downstream region revealed a single haplotype block
      that could be tagged by seven single nucleotide polymorphisms. These seven tags
      were typed in a group of T2D patients (n = 814) and a group of non-diabetic
      controls (n = 320) of white origin. A significant association was observed at 
      948C>A, with minor allele frequencies of 0.157 in T2D cases and 0.119 in non
      diabetic controls (p = 0.021). In a non-diabetic population (n = 630), the same 
      948 allele that conferred increased risk of T2D was significantly associated with
      higher plasma levels of fibrinogen and C-reactive protein (p = 0.0022 and 0.0038,
      respectively). However, no significant associations were observed with BMI, waist
      circumference, serum glucose levels, or fasting insulin levels. Our findings
      suggest that the visfatin/PBEF gene may play a role in determining T2D
      susceptibility, possibly by modulating chronic, low-grade inflammatory responses.

PMID- 17189537
TI  - Influence of metabolic syndrome on biomarkers of oxidative stress and
      inflammation in obese adults.
AB  - OBJECTIVE: Both obesity and the metabolic syndrome (MetS) have been independently
      linked with increased oxidative and inflammatory stress. This study tested the
      hypothesis that obesity with MetS is associated with greater oxidative and
      inflammatory burden compared with obesity alone. RESEARCH METHODS AND PROCEDURES:
      Forty-eight normal-weight and 40 obese (20 without MetS; 20 with MetS) adults
      were studied. MetS was defined according to National Cholesterol Education
      Program Adult Treatment Panel III criteria. Plasma concentrations of oxidized low
      density lipoprotein, C-reactive protein, tumor necrosis factor-alpha, interleukin
      (IL)-6, and IL-18 were determined by enzyme immunoassay. RESULTS: Plasma
      biomarkers of oxidative stress and inflammation were lowest in normal-weight
      controls. Of note, obese MetS adults demonstrated significantly higher plasma
      concentrations of oxidized low-density lipoprotein (62.3 +/- 3.2 vs. 54.0 +/- 4.0
      U/L; p < 0.05), C-reactive protein (3.0 +/- 0.6 vs. 1.5 +/- 0.3 mg/L; p < 0.01),
      tumor necrosis factor-alpha (2.1 +/- 0.1 vs. 1.6 +/- 0.1 pg/mL; p < 0.05), IL-6
      (2.8 +/- 0.4 vs. 1.4 +/- 0.2 pg/mL; p < 0.01), and IL-18 (253 +/- 16 vs. 199 +/-
      16 pg/mL; p < 0.01), compared with obese adults without MetS. DISCUSSION: These
      results suggest that MetS heightens oxidative stress and inflammatory burden in
      obese adults. Increased oxidative and inflammatory stress may contribute to the
      greater risk of coronary heart disease and cerebrovascular disease in obese
      adults with MetS.

PMID- 17189538
TI  - The figure rating scale as an index of weight status of women on videotape.
AB  - OBJECTIVE: To determine whether Stunkard's Figure Rating Scale (FRS) is a valid
      and reliable index of weight status when an unbiased observer assigns the figure
      ratings of adult women viewed on videotape. RESEARCH METHODS AND PROCEDURES:
      Seventy-two women drawn from a community sample participated in a videotaped
      study in which height and weight were measured. The FRS is a rating scale
      displaying 9 silhouettes ranging from very thin to very obese. Women were
      assigned a figure rating "in-person" by a research assistant (FRS used as a 17
      point scale) and by additional research assistants viewing women only on
      videotape (FRS used as both a 17- and 9-point scale). Pearson's correlation
      coefficients were calculated for in-person figure ratings, mean videotape figure
      ratings, and BMI. RESULTS: BMI and in-person figure ratings were highly
      correlated (r = 0.91), as were BMI and both mean 17-point videotape figure
      ratings and mean 9-point videotape figure ratings (r = 0.89 and 0.87,
      respectively). Inter-rater agreement for in-person figure ratings and mean 17
      point videotape figure ratings was 0.86, and agreement between in-person figure
      ratings and mean 9-point videotape figure ratings was 0.82. DISCUSSION: The FRS
      can be used as an index of women's weight status by an unbiased observer, with
      subjects viewed in-person or on videotape.

PMID- 17189539
TI  - Evidence for cytosolic p27(Kip1) ubiquitylation and degradation during adipocyte
      hyperplasia.
AB  - OBJECTIVE: Subcellular localization has been shown to play an important role in
      determining activity and accumulation of p27 protein during cell cycle
      progression. The purpose of this study was to examine p27 localization and
      ubiquitylation in relation to E3 ligase expression during adipocyte hyperplasia.
      RESEARCH METHODS AND PROCEDURES: This study used the murine 3T3-L1 preadipocyte
      model to examine p27 regulation during synchronous cell cycle progression. Cell
      lysates were isolated over time after hormonal stimulation, fractionated to
      cytosolic and nuclear compartments, and immunoblotted for relative protein
      determinations. RESULTS: Data presented in this study show that p27 was present
      in the cytosol and nucleus in density-arrested preadipocytes and that abundance
      in both compartments decreased in a phase-specific manner as preadipocytes
      synchronously re-entered the cell cycle during early phases of adipocyte
      differentiation. Blocking CRM1-mediated nuclear export did not prevent
      degradation, nor did it cause nuclear accumulation of p27, suggesting that
      distinct mechanisms mediating cytosolic and nuclear p27 degradation were
      involved. Treating preadipocytes with a potent and specific proteasome inhibitor
      during hormonal stimulation prevented Skp2 accumulation and p27(187)
      phosphorylation, which are essential events for SCF(Skp2) E3 ligase activity and
      nuclear p27 ubiquitylation during S/G(2) phase progression. Proteasome blockade
      also resulted in the first evidence of cytosolic p27 ubiquitylation during late
      G(1) phase as preadipocytes undergo the transition from quiescence to
      proliferation. DISCUSSION: These data are consistent with the postulate that p27
      is ubiquitylated and targeted for degradation by the 26S proteasome in a phase
      specific manner by distinct ubiquitin E3 ligases localized to the cytosol and
      nucleus during adipocyte hyperplasia.

PMID- 17189540
TI  - A high-fat diet has a tissue-specific effect on adiponectin and related enzyme
      expression.
AB  - OBJECTIVE: This study was designed to test whether adiponectin plays a role in
      diet-induced obesity and insulin resistance and acts as a mediator to induce or
      inhibit specific metabolic pathways involved in lipid metabolism RESEARCH METHODS
      AND PROCEDURES: Forty C57BL/6J male mice were fed either a high-fat (HF) or
      control diet for 4 months, and adiponectin, its receptors, and enzyme expression
      in liver and muscle tissue were measured. RESULTS: Mice fed the HF diet exhibited
      significantly greater weight gain, abnormal oral glucose tolerance test curves,
      and elevated homeostasis model assessment of insulin resistance (5.3 +/- 0.89 vs.
      2.8 +/- 0.39). A significant reduction of adiponectin RNA expression (51%) and
      protein levels (15%) was observed in the adipose tissue of HF animals; however,
      serum adiponectin levels did not differ between groups (7.12 +/- 0.34 mug/mL vs.
      6.44 +/- 0.38 microg/mL). Expression of hepatic mRNA of AdipoR1 and AdipoR2 was
      reduced by 15% and 25%, respectively, in animals fed the HF diet. In contrast,
      receptor mRNA expression of AdipoR1 and AdipoR2 increased by 25% and 30%,
      respectively, in muscle tissue. No effect was found on hepatic adenosine
      monophosphate-activated protein kinase expression; however, a significant
      reduction of phosphoadenosine monophosphate kinase levels in muscles was
      observed. Hepatic acetyl-coenzyme A carboxylase was similar between groups, but
      in muscles, the inactive form phosphoacetyl-coenzyme A carboxylase was
      significantly reduced (p < 0.05). DISCUSSION: The HF diet led to decreased
      insulin sensitivity accompanied by impaired activity of adiponectin-related
      enzymes in skeletal muscles but not in the liver. These results suggest that the
      HF diet has a tissue-specific effect on adiponectin and associated enzyme
      expression.

PMID- 17189541
TI  - Increase of neuronal histamine in obese rats is associated with decreases in body
      weight and plasma triglycerides.
AB  - OBJECTIVE: The purpose of the present study was to examine the metabolic effects
      of a specific histamine H(3) receptor antagonist, the cinnamic amide NNC 0038
      0000-1202 (NNC 38-1202). RESEARCH METHODS AND PROCEDURES: Effects of NNC 38-1202
      on paraventricular levels of histamine and acute effects on food intake were
      followed in normal rats, whereas effects on body weight homeostasis and lipid
      metabolism were studied in a rat model of diet-induced obesity (DIO). RESULTS:
      NNC 38-1202, administered as single oral doses of 15 and 30 mg/kg, significantly
      (p < 0.01) increased paraventricular histamine by 339 +/- 54% and 403 +/- 105%,
      respectively, compared with basal levels. The same doses produced significant (p
      < 0.01) reductions in food intake. In DIO rats receiving NNC 38-1202 in a daily
      dose of 5 mg/kg for 22 days, a decrease in food intake was associated with a
      significant (p < 0.001) net loss of body weight (-11.0 +/- 4.8 grams), compared
      with rats receiving vehicle, which gained 13.6 +/- 3.0 grams. Also, NNC 38-1202
      significantly (p < 0.05) reduced plasma triglycerides by approximately 42%, in
      parallel with increases in plasma free fatty acids and beta-hydroxybutyrate
      levels. Despite reductions in food intake and body weight following
      administration of NNC 38-1202, no sign of a decrease in energy expenditure was
      observed, and whole-body lipid oxidation was significantly (p < 0.05) increased
      in the period after dosing. DISCUSSION: The present study suggests that
      antagonistic targeting of the histamine H(3) receptor decreases food intake, body
      weight, and plasma TG levels and, thus, represents an interesting approach to
      treatment of obesity and associated hyperlipidemia.

PMID- 17189543
TI  - The growth of children in relation to the timing of obesity development.
AB  - OBJECTIVE: To examine whether there is an association between the timing of the
      development of obesity and children's growth. RESEARCH METHODS AND PROCEDURES:
      This study investigated 141 prepubertal obese children (76 girls) and 72 healthy
      non-obese children (39 girls). The target height standard deviation score (SDS),
      the percentage weight for height, and the height SDS (H-SDS) at presentation and
      at the age of 2 years were calculated. Patients were classified, according to
      whether obesity developed before or after the age of 3 years, as presenting with
      early-onset or late-onset obesity, respectively. RESULTS: Mean age (+/-SD) at
      presentation was 9.4 (2.1) years. At the age of 2 years, the H-SDS of the
      children with early-onset obesity was 1.3 (1.0) vs. 0.9 (1.3) for the late-onset
      obese (p > 0.5) and 0.4 (1.0) for controls (p < 0.001), and the children with
      late-onset obesity were also significantly taller than controls (p < 0.005). At
      presentation, children with early-onset obesity were significantly taller than
      children with late-onset obesity [1.1 (0.8) vs. 0.6 (1.0); p < 0.001] and
      controls [0.2 (0.8); p < 0.001]. There was no increase in H-SDS after the age of
      2 years in the late-onset obese children (p > 0.05). H-SDS values were below
      average in 21% of the children with late-onset obesity and in only 4% of the
      children with early-onset obesity. DISCUSSION: These findings indicate that late
      development of obesity is not associated with increased stature in prepubertal
      children; however, it may be preceded by growth acceleration in the early years
      of life. Growth acceleration in early life may be a predictor for future obesity.

PMID- 17189542
TI  - Acute modulation of adipose tissue lipolysis by intravenous estrogens.
AB  - OBJECTIVE: The aim of this study was to determine whether intravenous (IV)
      conjugated estrogens (EST) acutely enhance the suppression of whole-body or
      regional subcutaneous adipose tissue (SAT) lipolysis by insulin in postmenopausal
      women. RESEARCH METHODS AND PROCEDURES: We assessed whole-body lipolysis by
      [(2)H(5)]glycerol rate of appearance (Glyc(RA)) and abdominal and femoral SAT
      lipolysis (interstitial glycerol; Glyc(IS)) by subcutaneous microdialysis.
      Postmenopausal women (n = 12) were studied on two occasions, with IV EST or
      saline control (CON), under basal conditions and during a 3-stage (4, 8, and 40
      mU/m(2)/min) hyperinsulinemic, euglycemic clamp. Ethanol outflow/inflow ratio and
      recovery of [(13)C]glycerol during microdialysis were used to assess blood flow
      changes and interstitial glycerol concentrations, respectively. RESULTS: Compared
      with CON, EST did not affect systemic basal or insulin-mediated suppression of
      lipolysis (Glyc(RA)) or SAT nutritive blood flow. Basal Glyc(IS) in SAT was
      reduced on the EST day. However, insulin-mediated suppression of lipolysis in SAT
      was not significantly influenced by EST. DISCUSSION: These findings suggest that
      estrogens acutely reduce basal lipolysis in SAT through an unknown mechanism but
      do not alter whole-body or SAT suppression of lipolysis by insulin.

PMID- 17189544
TI  - Comparison of metabolic risk factors between severely and very severely obese
      patients.
AB  - OBJECTIVE: A prospective clinical intervention study was performed to estimate
      the metabolic risk factors in patients with very severe obesity (VSO) vs. severe
      obesity (SO). RESEARCH METHODS AND PROCEDURES: Two hundred twenty-eight VSO (BMI
      > or = 50 kg/m(2)) and 221 SO patients (BMI = 40 to 49.9 kg/m(2)) participated in
      the study (367 women and 82 men). Metabolic measurements included plasma lipids,
      glucose and insulin, hemoglobin A(1c), leptin, and sex hormones, as well as
      hepatic steatosis in a subgroup of patients. Subgroups of patients with non
      insulin-dependent diabetes and hyperlipidemia (HLP) were examined. RESULTS: The
      most unexpected result of our study was that VSO men showed significantly better
      lipid profiles than SO men. Furthermore, 18% of VSO men had no metabolic
      aberrations, whereas all SO men did. The advantageous metabolic status of VSO men
      was associated with sex hormone changes that favor gynoid fat distribution. The
      beneficial metabolic situation with VSO seems to be sex specific for men.
      DISCUSSION: This study shows that the metabolic situation in VSO is not more
      severe than in the less obese cohort. These findings distinctly differ from the
      positive associations that have previously been reported between BMI, lipids, and
      other metabolic indices among individuals whose BMI is <40 kg/m(2).

PMID- 17189545
TI  - Leptin, superoxide dismutase, and weight loss: initial leptin predicts weight
      loss.
AB  - OBJECTIVE: Our goal was to study how plasma leptin concentration, superoxide
      dismutase (SOD) activity, and weight loss are related in obese adults. RESEARCH
      METHODS AND PROCEDURES: Serum leptin concentration, SOD activities, general
      biochemical data, and body composition measurements were obtained for 62
      overweight and obese subjects before and after an 8-week body weight reduction
      (BWR) regimen. The subjects were on dietary control, performed moderate aerobic
      and strength training exercises, and attended educational lectures. RESULTS: The
      measurement results indicated that the following criteria were significantly
      reduced: body weight [84.4 +/- 17.0 vs. 79.3 +/- 16.1 (standard error) kg, p <
      0.001]; BMI (31.5 +/- 4.3 vs. 29.4 +/- 4.2 kg/m(2), p < 0.001), and fat mass
      (33.3 +/- 10.0 vs. 29.8 +/- 10.4 kg, p < 0.001). Plasma leptin levels also
      significantly decreased from 31.5 +/- 17.6 to 26.5 +/- 17.2 ng/mL (p < 0.001).
      Additionally, SOD activity was significantly increased from 261.4 +/- 66.0 to
      302.7 +/- 30.9 U/mL (p < 0.001). Based on linear regression analysis results, a
      3.78- to 8.13-kg reduction in weight can be expected after the 8-week BWR regimen
      when initial leptin concentration was 5 to 30 ng/mL. DISCUSSION: We found that an
      8-week exercise and diet program was effective in reducing weight and fat mass
      and, notably, had further beneficial effects on leptin resistance and SOD
      activity. Additionally, this study demonstrated that initial plasma leptin
      concentration may be used as a predictor for weight loss outcome.

PMID- 17189546
TI  - Mitochondrial DNA depletion in small- and large-for-gestational-age newborns.
AB  - OBJECTIVE: To investigate whether mitochondrial DNA (mtDNA) content may be
      associated with clinical features, anthropometric variables, and laboratory
      findings in both extremes of abnormal fetal growth: small and large size for
      gestational age. RESEARCH METHODS AND PROCEDURES: Eighty-eight pregnant women and
      their infants were included in a cross-sectional study. According to the
      offspring birthweight, normalized by sex and gestational age, there were 57
      newborns with appropriate weight for gestational age (AGA) and 31 with abnormal
      weight for gestational age: 17 small for gestational age (SGA) and 14 large for
      gestational age (LGA). mtDNA quantification using nuclear DNA as a reference was
      measured by a real-time quantitative polymerase chain reaction method. RESULTS:
      The mothers' pregestational BMI was associated with the weight of their
      offspring: SGA infants had lean mothers (BMI, 21.4 +/- 0.7), and LGA infants had
      overweight mothers (BMI, 26.7 +/- 1.4) in comparison with AGA infants (BMI, 23.0
      +/- 0.7) (p < 0.003). Newborn leptin levels were associated with birthweight
      after adjustment for sex and gestational age (SGA, 7.0 +/- 1.1 ng/mL; AGA, 15.2
      +/- 1.6 ng/mL; and LGA, 25.6 +/- 4.1 ng/mL) (p < 0.002). Conversely,
      mtDNA/nuclear DNA ratio was significantly lower in both extremes of abnormal
      fetal growth, SGA (18 +/- 6) and LGA (9 +/- 2), at birth in comparison to AGA
      weight infants (28 +/- 4) (p < 0.03). DISCUSSION: Our findings show that mtDNA
      content is decreased in newborns with abnormal weight in comparison with AGA
      infants. On the basis of a cumulative body of evidence, we speculate that mtDNA
      depletion is one of the putative links between abnormal fetal growth and
      metabolic and cardiovascular complications in later life.

PMID- 17189547
TI  - The effects of the dietary glycemic load on type 2 diabetes risk factors during
      weight loss.
AB  - OBJECTIVE: To compare the effects of two calorie-restricted diets that differ in
      glycemic load (GL) on glucose tolerance and inflammation. RESEARCH METHODS AND
      PROCEDURES: Thirty-four healthy overweight adults, ages 24 to 42 years, were
      randomized to 30% provided calorie-restricted diets with high (HG) or low (LG)
      glycemic load for 6 months. Outcomes were changes in glucose-insulin dynamics and
      C-reactive protein (CRP) levels. RESULTS: Compared with baseline, levels of
      fasting insulin, homeostasis model assessment of insulin resistance, post-load
      insulin at 30 minutes, and incremental area-under-the-curve-insulin during the
      oral glucose tolerance test were significantly lower in both groups at 6 months
      (p range, 0.01 to 0.05), but after adjustment for baseline values and weight
      change, there were no differences between the two groups with regard to changes
      over time in any parameter. The mean percentage change in insulin sensitivity by
      a frequently sampled intravenous glucose tolerance test was +26% in the HG group
      and +24% in the LG group (p = 0.83); first-phase acute insulin release was -20%
      in the HG group and -21% in the LG group (p = 0.77). More participants on the LG
      diet (14 of 16 subjects) had a decline in serum CRP, compared with those on the
      HG diet (7 of 16 subjects) (p < 0.05). DISCUSSION: In healthy overweight adults
      provided with food for 6 months, the dietary GL did not seem to influence chronic
      adaptations in glucose-insulin dynamics above that associated with weight loss.
      This finding highlights the importance of absolute weight loss over the dietary
      macronutrient composition used to achieve weight loss. The finding of greater
      declines in CRP concentration after consumption of a low-GL diet warrants further
      investigation.

PMID- 17189548
TI  - A workplace intervention to promote stair climbing: greater effects in the
      overweight.
AB  - OBJECTIVE: Stair climbing is a lifestyle physical activity that uses more
      calories per minute than jogging. This study tested an intervention designed to
      promote stair climbing in a workplace. Because previous studies provide only
      equivocal evidence of the effects of increased stair climbing in worksites, a
      formal comparison of the effects of the intervention on stair ascent and descent
      was made. RESEARCH METHODS AND PROCEDURES: In a five-story public sector
      building, a 2-week baseline was followed by 6 weeks of an intervention involving
      a 23(1/2)- x 16(1/2)-inch poster in the lobby, the same poster and six messages
      affixed to the stair risers between floors, and an 11(3/4)- x 8(1/4)-inch point
      of-choice prompt at the elevators. Stair and elevator choices (n = 26,806) were
      videotaped throughout and subsequently coded for direction of travel, traveler's
      sex, and traveler's load. Weight status was coded using silhouettes beside the
      computer monitor. RESULTS: A significant effect of the intervention on stair
      climbing was greater in those coded as overweight (+5.4%; odds ratio = 1.33) than
      in individuals of normal weight (+2.5%; odds ratio = 1.12). Although stair
      descent was more common than ascent, the intervention had similar effects for
      both directions of travel. DISCUSSION: Stair climbing at work has few barriers
      and seems to be a type of physical activity that is acceptable to overweight
      individuals. The relatively weak effect of workplace interventions compared with
      results for public access staircases may reflect uncontrolled effects such as the
      immediate availability of the elevator for the traveler.

PMID- 17189549
TI  - Evaluation of a multisensor armband in estimating energy expenditure in obese
      individuals.
AB  - OBJECTIVE: To examine the reliability and validity of the SenseWear Pro 2 Armband
      (SWA; Body Media, Pittsburgh, PA) during rest and exercise compared with indirect
      calorimetry (IC) in obese individuals. RESEARCH METHODS AND PROCEDURES: Energy
      expenditure was assessed during rest with the SWA and IC in 142 obese adults (37
      men and 105 women, BMI = 42.3 +/- 7.0) and in 25 lean and overweight adults (BMI
      = 25.3 +/- 3.2) who were used as a comparison group. Twenty-nine of the obese
      adults also participated in three separate short exercise sessions including
      cycle ergometry, stair stepping, and treadmill walking. RESULTS: The
      repeatability of SWA estimates in obese subjects was high (r = 0.88, p < 0.001).
      The SWA generally underestimated the resting energy expenditure (REE) (1811 +/-
      346 vs. 1880 +/- 382 kcal/d) and highly overestimated the energy expenditure
      during the exercise sessions in obese individuals. REE estimations by SWA were
      significantly correlated with fat-free mass (r = 0.88, p < 0.001). Bland-Altman
      plots based statistical analysis for the estimated REE, and measured IC showed a
      low agreement (Total Error > 20% but Systematic Error < 5%) between the two
      methods in obese subjects, although they showed a high correlation and a very
      good agreement in lean and overweight patients. DISCUSSION: The SWA is an easy to
      handle, practical, new portable device for measuring energy expenditure. The
      accuracy of the SWA appeared to be poor in the obese subjects we examined,
      especially those with high REE both in rest and exercise. We believe that it is
      necessary to incorporate new, obesity-specific algorithms in the relative
      software.

PMID- 17189550
TI  - Antioxidant supplementation lowers exercise-induced oxidative stress in young
      overweight adults.
AB  - OBJECTIVE: To determine whether antioxidant (AOX) supplementation attenuates post
      exercise oxidative stress and contributors to oxidative stress (inflammation,
      blood lipids) in overweight young adults. RESEARCH METHODS AND PROCEDURES: This
      was a randomized, double-blind, controlled study. Overweight (BMI, 33.2 +/- 1.9
      kg/m(2)) and comparative normal-weight (BMI, 21.9 +/- 0.5 kg/m(2)) adults 18 to
      30 years old (total N = 48) were enrolled. Participants received either daily
      antioxidant (AOX) treatment (800 IU of vitamin E, 500 mg of vitamin C, 10 mg of
      beta-carotene) or placebo (PL) for 8 weeks for a total of four groups. All
      participants completed a standardized 30-minute cycle exercise bout at baseline
      and 8 weeks. Exercise-induced changes in lipid hydroperoxide (DeltaPEROX), C
      reactive protein (DeltaCRP), interleukin-6 (DeltaIL-6), cholesterol subfractions,
      triglycerides, total AOX status (DeltaTAS), and adiponectin were assessed.
      RESULTS: Exercise-induced DeltaPEROX was lower in the overweight-AOX group (0.09
      nM/kg per min) compared with PL-treated overweight and normal-weight groups
      (0.98, 0.53 nM/kg per min) by 8 weeks (p < 0.05). Adiponectin was increased in
      both overweight and normal-weight AOX groups (22.1% vs. 3.1%; p < 0.05) but
      reduced in PL groups. DeltaIL-6, Deltatotal cholesterol, and Deltalow-density
      lipoprotein-cholesterol concentrations during exercise were lower in the AOX
      treated groups compared with PL groups (all p < 0.05). After controlling for BMI,
      the Deltatotal cholesterol, Deltalow-density lipoprotein-cholesterol,
      Deltaadiponectin, and DeltaTAS explained 59.1% of the variance of the regression
      model of the DeltaPEROX by 8 weeks (total model R(2) = 0.600; p = 0.015).
      DISCUSSION: AOX lowers exercise-induced oxidative stress in overweight adults.
      Inflammatory and lipid markers may also be attenuated with AOX. Further studies
      are needed to determine whether AOX may be used in cardiovascular disease
      prevention in the overweight population.

PMID- 17189551
TI  - Does dieting lead to weight gain? A four-year longitudinal study of middle school
      girls.
AB  - OBJECTIVE: A majority of the published longitudinal research on children has
      reported that dieting is related to weight gain at a later point in time. The
      purpose of this study was to look at weight control behaviors and patterns of
      weight gain and loss, specifically whether dieting is related to weight gain.
      RESEARCH METHODS AND PROCEDURES: Baseline data were collected from 1358 female
      students in grades 6 to 9 from schools in Hayward, CA, and Tucson, AZ. Data were
      obtained annually over a 4-year period. Paper-and-pencil questionnaires and
      height and weight were obtained during the students' regular classroom periods.
      Dieting was measured both with the single item, "In the past year, how often have
      you been on a diet to lose weight?" scored from "never" to "always," and with a
      Dieting Behavior Scale including five items on weight control behaviors. Changes
      in BMI z-scores were analyzed. RESULTS: On average, girls who reported "never"
      dieting were most likely to have an increased BMI z-score at the next
      measurement, and those who reported "always" dieting were most likely to have a
      decreased BMI z-score. The same pattern was true for the Dieting Behavior Scale.
      DISCUSSION: Our finding that dieting and weight gain were not related,
      independently of initial BMI, does not mean that dieting to lose weight is
      appropriate, especially among young girls. Additional research is needed both to
      examine this relationship and to determine exactly what behaviors children are
      engaging in when they report that they are dieting.

PMID- 17189552
TI  - Effect of 1-year dairy product intervention on fat mass in young women: 6-month
      follow-up.
AB  - OBJECTIVE: Previous results from this laboratory suggest that a 1-year dairy
      intake intervention in young women does not alter fat mass. The objective of this
      study was to determine the impact of the 1-year dairy intervention 6 months after
      completion of the intervention. RESEARCH METHODS AND PROCEDURES: Previously,
      normal-weight young women (n = 154) were randomized to one of three calcium
      intake groups: control (<800 mg/d), medium dairy (1000 to 1100 mg/d), or high
      dairy (1300 to 1400 mg/d) for a 1-year trial (n = 135 completed). In the current
      study, 51 women were assessed 6 months after completion of the intervention
      trial. Body compositions (body fat, lean mass) were measured using DXA. Self
      report questionnaires were utilized to measure activity and dietary intake
      (kilocalories, calcium). RESULTS: The high-dairy group (n = 19) maintained an
      elevated calcium intake (1027 +/- 380 mg/d) at 18 months compared with the
      control group (n = 18, 818 +/- 292; p = 0.02). Mean calcium intake over the 18
      months predicted a negative change in fat mass (p = 0.04) when baseline BMI was
      controlled in regression analysis (model R(2) = 0.11). 25-Hydroxyvitamin D levels
      were correlated with fat mass at each time-point (baseline, r = -0.41, p = 0.003;
      12 months, r = -0.42, p = 0.002; 18 months, r = -0.32, p = 0.02) but did not
      predict changes in fat mass. DISCUSSION: Dietary calcium intake over 18 months
      predicted a negative change in body fat mass. Thus, increased dietary calcium
      intakes through dairy products may prevent fat mass accumulation in young,
      healthy, normal-weight women.

PMID- 17189554
TI  - Physical activity compliance: differences between overweight/obese and normal
      weight adults.
AB  - OBJECTIVES: Comparisons of physical activity measured by accelerometers in
      overweight/obese adults and their normal-weight counterparts are limited.
      Compliance with the 2002 Institute of Medicine (IOM) exercise recommendations for
      60 minutes of moderate-intensity exercise daily has not been reported. The
      purpose of this study was to compare physical activity, as measured by
      accelerometers, in overweight/obese adults vs. normal-weight controls and to
      assess compliance with recommendations for physical activity by the IOM in 2002
      and by the Centers for Disease Control and Prevention and American College of
      Sports Medicine in 1995 for 30 minutes of moderate-intensity activity, preferably
      all days of the week. RESEARCH METHODS AND PROCEDURES: Sixty-two overweight/obese
      subjects, BMI > or = 25, included 31 adults, 12 men and 19 women, 25 to 69 years
      old, and their normal-weight controls, BMI 18.5 to 24.9, matched for gender, age,
      and height. Body composition was assessed using DXA. Physical activity was
      measured with Actigraph accelerometers (MTI, Fort Walton Beach, FL) worn by each
      participant for 7 consecutive days. RESULTS: Accelerometry data indicated that
      overweight/obese adults recorded approximately 60 counts per minute less per day
      and spent 21 minutes less engaged in moderate or greater intensity activity than
      their normal-weight counterparts. Although 71% to 94% of those studied met 1995
      recommendations, only 13% of overweight/obese subjects and 26% of normal-weight
      participants met 2002 exercise recommendations. DISCUSSION: These results suggest
      that daily minutes spent in moderate-intensity activity or greater are associated
      with weight status and that the 2002 IOM recommendations may be difficult to meet
      even for normal-weight individuals.

PMID- 17189553
TI  - Psychological status and weight-related distress in overweight or at-risk-for
      overweight children.
AB  - OBJECTIVE: To associate psychological status, weight-related distress, and weight
      status during childhood in overweight or at-risk-for-overweight children.
      RESEARCH METHODS AND PROCEDURES: We associated self-report of depression, trait
      anxiety, and weight-related distress (body size dissatisfaction and weight
      related peer teasing after controlling for the effects of weight) in 164 children
      (black 35%; age 11.9 +/- 2.5 years; girls 51%) who were overweight or at-high
      risk-for-overweight and were not seeking weight loss. RESULTS: Overall, heavier
      children reported more psychological and weight-related distress. Black children
      reported more anxiety and body size dissatisfaction than white children, despite
      equivalent weights. However, psychological distress was not significantly
      associated with weight in white children. Girls reported more weight-related
      distress than boys. Depression was associated with weight-related teasing in all
      predictive models, except in the model using only black subjects. Trait anxiety
      was associated with report of peer teasing when using all subjects. Depression
      was also significantly associated with children's report of body size
      dissatisfaction in models using all subjects, only girls, or white subjects, but
      not in analyses using only boys or black subjects. For boys peer teasing was
      associated with body size dissatisfaction. In models including only black
      children, depression and trait anxiety were not significantly associated with
      either report of peer teasing or body size dissatisfaction. DISCUSSION:
      Regardless of race or sex, increasing weight is associated with emotional and
      weight-related distress in children. However, associations of psychological
      status, weight, and weight-related distress differ for girls and boys, and for
      black and white children.

PMID- 17189555
TI  - Frequency of family dinner and adolescent body weight status: evidence from the
      national longitudinal survey of youth, 1997.
AB  - OBJECTIVE: To explore associations between overweight status and the frequency of
      family dinners (FFD) for adolescents and how those associations differ across
      race and ethnicity. RESEARCH METHODS AND PROCEDURES: A sample of 5014 respondents
      between 12 and 15 years of age from the 1997 wave of the National Longitudinal
      Survey of Youth 1997 (NLSY97) was used. BMI was calculated using self-reported
      height and weight; 13.3% of respondents qualified as overweight, 16.4% qualified
      as at-risk-of-overweight, and 1.9% qualified as underweight. The remainder were
      normal weight. FFD was defined as the number of times respondents had dinner with
      their families in a typical week in the past year. Multinomial logistic
      regression models were estimated separately for non-Hispanic whites vs. blacks
      and Hispanics for odds of belonging to the other weight categories compared with
      normal weight. A supplementary longitudinal analysis estimated the odds of change
      in overweight status between 1997 and 2000. RESULTS: In 1997, the FFD
      distribution was as follows: 0, 8.3%; 1 or 2, 7.3%; 3 or 4, 13.4%; 5 or 6, 28.1%;
      7, 42%. For whites, higher FFD was associated with reduced odds of being
      overweight in 1997, reduced odds of becoming overweight, and increased odds of
      ceasing to be overweight by 2000. No such associations were found for blacks and
      Hispanics. DISCUSSION: Reasons for racial and ethnic differences in the
      relationship between FFD and overweight may include differences in the types and
      portions of food consumed at family meals. More research is needed to verify
      this.

PMID- 17189556
TI  - Effect of sarcopenia on cardiovascular disease risk factors in obese
      postmenopausal women.
AB  - OBJECTIVE: To compare sarcopenic-obese and obese postmenopausal women for risk
      factors predisposing to cardiovascular disease (CVD) and determine whether there
      may be a relationship between muscle mass and metabolic risk in obese
      postmenopausal women. RESEARCH METHODS AND PROCEDURES: In this cross-sectional
      study, 22 healthy obese postmenopausal women (mean age, 66 +/- 5 years; mean BMI,
      27 +/- 3 kg/m(2)) were divided into two groups matched for age (+/-2 years) and
      fat mass (FM) (+/-2%). Sarcopenia was defined as a muscle mass index of <14.30 kg
      fat-free mass (FFM)/m(2) (which corresponds to 1 standard deviation below the
      values of a young reference population), and obesity was defined as an FM of >35%
      (which corresponds to the World Health Organization guidelines). FM, FFM
      (measured by DXA), daily energy expenditure (accelerometry), dietary intake (3
      day dietary record), and blood biochemical analyses (lipid profile, insulin,
      glucose, and C-reactive protein) were obtained. Visceral fat mass (VFM) was
      calculated by the equation of Bertin, which estimates VFM from DXA measurements.
      RESULTS: Obese women had more FFM (p = 0.006), abdominal FM (p = 0.047), and VFM
      (p = 0.041) and a worse lipid profile [p = 0.040 for triglycerides; p = 0.004 for
      high-density lipoprotein (HDL); p = 0.026 for total cholesterol/HDL] than
      sarcopenic-obese postmenopausal women. Obese women also ingested significantly
      more animal (p = 0.001) and less vegetal proteins (p = 0.013), although both
      groups had a similar total protein intake (p = 0.967). DISCUSSION: Sarcopenia
      seems to be associated with lower risk factors predisposing to CVD in obese
      postmenopausal women. With the increase in the number of aging people, the health
      implications of being sarcopenic-obese merit more attention.

PMID- 17189558
TI  - Reverse causality and confounding and the associations of overweight and obesity
      with mortality.
AB  - OBJECTIVE: To examine the effect of reverse causality and confounding on the
      association of BMI with all-cause and cause-specific mortality. RESEARCH METHODS
      AND PROCEDURES: Data from two large prospective studies were used. One (a
      community-based cohort) included 8327 women and 7017 men who resided in two
      Scottish towns at the time of the baseline assessment in 1972-1976; the other (an
      occupational cohort) included 4016 men working in the central belt of Scotland at
      the time of the baseline assessment in 1970-1973. Participants in both cohorts
      were ages 45 to 64 years at baseline; the follow-up period was 28 to 34 years.
      RESULTS: In age-adjusted analyses that did not take account of reverse causality
      or smoking, there was no association between being overweight (BMI 25 to <30
      kg/m(2)) and mortality, and weak to modest associations between obesity (BMI > or
      =30 kg/m(2)) and mortality. There was a strong association between smoking and
      lower BMI in women and men in both cohorts (all p < 0.0001). Among never-smokers
      and with the first 5 years of deaths removed, overweight was associated with an
      increase in all-cause mortality (relative risk ranging from 1.12 to 1.38), and
      obesity was associated with a doubling of risk in men in both cohorts (relative
      risk, 2.10 and 1.96, respectively) and a 60% increase in women (relative risk,
      1.56). In both never-smokers and current smokers, being overweight or obese was
      associated with important increases in the risk of cardiovascular disease.
      DISCUSSION: These findings demonstrate that with appropriate control for smoking
      and reverse causality, both overweight and obesity are associated with important
      increases in all-cause and cause-specific mortality, and in particular with
      cardiovascular disease mortality.

PMID- 17189559
TI  - Is there an anti-fat bias among schizophrenia patients?

PMID- 17189557
TI  - Smoking during pregnancy and offspring fat and lean mass in childhood.
AB  - OBJECTIVE: Maternal smoking during pregnancy has been shown to be associated with
      obesity in the offspring, but findings have been based mainly on BMI, which is
      derived from height and weight. This study examined the association between
      maternal and partner smoking during pregnancy and offspring total fat, truncal
      fat, and lean mass in childhood. RESEARCH METHODS AND PROCEDURES: Analysis was
      based on 5689 white singletons born in 1991-1992 and enrolled in the Avon
      Longitudinal Study of Parents and Children, with maternal smoking data recorded
      for at least one trimester in pregnancy and their own body composition assessed
      by DXA at mean age 9.9 years. RESULTS: Smoking at any time during pregnancy was
      associated with higher offspring BMI [0.18 (95% confidence interval, 0.12 to
      0.25) standard deviation units] and total fat mass [0.17 (95% confidence
      interval, 0.12 to 0.23) standard deviation units], after adjustment for age, sex,
      height, and height squared for total fat mass. These associations were not
      attenuated by adjustment for the confounding factors that were measured. Maternal
      smoking was also associated with lean mass and, to a lesser extent, truncal fat
      mass. Associations with partner's smoking were in the same direction but weaker
      than those of the mother's for all outcomes. DISCUSSION: Maternal smoking at any
      time during pregnancy is associated with higher offspring total fat mass at mean
      age 9.9 years. However, as the associations with partner smoking were only a
      little weaker than those with maternal smoking, confounding by social factors
      rather than a direct effect of maternal smoking is a possible explanation.

PMID- 17189563
TI  - Exploration, normalization, and genotype calls of high-density oligonucleotide
      SNP array data.
AB  - In most microarray technologies, a number of critical steps are required to
      convert raw intensity measurements into the data relied upon by data analysts,
      biologists, and clinicians. These data manipulations, referred to as
      preprocessing, can influence the quality of the ultimate measurements. In the
      last few years, the high-throughput measurement of gene expression is the most
      popular application of microarray technology. For this application, various
      groups have demonstrated that the use of modern statistical methodology can
      substantially improve accuracy and precision of the gene expression measurements,
      relative to ad hoc procedures introduced by designers and manufacturers of the
      technology. Currently, other applications of microarrays are becoming more and
      more popular. In this paper, we describe a preprocessing methodology for a
      technology designed for the identification of DNA sequence variants in specific
      genes or regions of the human genome that are associated with phenotypes of
      interest such as disease. In particular, we describe a methodology useful for
      preprocessing Affymetrix single-nucleotide polymorphism chips and obtaining
      genotype calls with the preprocessed data. We demonstrate how our procedure
      improves existing approaches using data from 3 relatively large studies including
      the one in which large numbers of independent calls are available. The proposed
      methods are implemented in the package oligo available from Bioconductor.

PMID- 17189562
TI  - Effect of smoking conditions and methods of collection on the mutagenicity and
      cytotoxicity of cigarette mainstream smoke.
AB  - There is a history for the use of in vitro bioassays to assess the toxicological
      properties of mainstream cigarette smoke (MSS). The results described in the
      literature were, for the most part, obtained with MSS collected under Federal
      Trade Commission (FTC) or International Organization for Standardization (ISO)
      conditions. However, numerous studies have shown that smokers smoke their
      cigarettes more intensely (e.g., they take larger puffs and/or more frequent
      puffs and/or partially occlude filter ventilation) than they are smoked on
      smoking machines operated under FTC (or ISO) conditions. It has also been
      reported that MSS composition changes with changes in smoking conditions.
      Furthermore, some governmental agencies have adopted regulations that specify
      more intensive protocols (i.e., Health Canada Intensive, HCI) for the collection
      of MSS for in vitro toxicological assays. Consequently, the performance of the
      Ames assay (TA98+S9, TA100+S9) and neutral red uptake assay under ISO and HCI
      protocols was studied with two blended (KR1R4F/KR2R4F, KR1R5F) and one flue-cured
      (CIM-7) reference cigarettes. The main outcome was when results were reported on
      a per milligram TPM (that portion of the mainstream smoke which is trapped in the
      smoke trap, expressed as milligrams per cigarette) basis generated under ISO
      conditions was more mutagenic and more cytotoxic than was TPM generated under HCI
      conditions. However, the decrease in biological activity could not be explained
      only by the increased in the water content of the TPM on going from ISO to HCI
      smoking conditions, and the results may be influenced by differences in smoke
      chemistry as a result of differing smoke collection systems.

PMID- 17189564
TI  - FDA advisers endorse Celebrex for juvenile rheumatoid arthritis: lack of studies
      in children raises safety concerns.

PMID- 17189565
TI  - Outpatient payment rule revised for 2007.

PMID- 17189566
TI  - Certification program for inpatient electronic health records expected in 2007.

PMID- 17189568
TI  - Issues in medication safety.

PMID- 17189569
TI  - Issues in medication safety.

PMID- 17189571
TI  - Issues in medication safety.

PMID- 17189574
TI  - Transdermal patient-controlled analgesia.

PMID- 17189575
TI  - Developing standard concentrations in the neonatal intensive care unit.

PMID- 17189576
TI  - Managing an institutional patient assistance program in the Part D environment.

PMID- 17189577
TI  - Improving the quality of care for coronary artery disease.

PMID- 17189578
TI  - Sedation and analgesia in the intensive care unit: evaluating the role of
      dexmedetomidine.
AB  - PURPOSE: A review highlighting the application of sedatives and analgesics in the
      intensive care unit (ICU) setting, with a focus on the use of dexmedetomidine, is
      presented. SUMMARY: Relevant and applicable clinical trials that resulted from a
      search of the literature from 1966 to July 2006 using key search terms such as
      dexmedetomidine, intensive care unit, sedation, delirium, and analgesia were
      evaluated. Many agents have been evaluated in the search of the optimal regimen
      for sedation and analgesia in the ICU, including opioids, benzodiazepines,
      propofol, and antipsychotic agents. Dexmedetomidine has demonstrated efficacy as
      a sedative analgesic on the basis of its ability to lower opioid, benzodiazepine,
      and propofol requirements in clinical trials. The role of dexmedetomidine in ICU
      clinical practice is limited because of a lack of mortality and other morbidity
      endpoints, such as ICU length of stay, hospital length of stay, time to
      extubation, long-term complications after discharge from the ICU, and delirium.
      The most commonly reported adverse effects of dexmedetomidine are secondary to
      its effects as an alpha(2)-receptor agonist and are cardiac in nature. A detailed
      cost analysis may be warranted to justify the relatively high acquisition cost of
      dexmedetomidine. CONCLUSION: Dexmedetomidine may be an effective agent for ICU
      sedation and analgesia. However, the lack of clinically relevant endpoints in
      trials, the concern about adverse cardiovascular effects, and the relatively high
      acquisition cost of this drug limit its use to a select number of patients who
      may benefit from its distinguished mechanism of action.

PMID- 17189579
TI  - Lead toxicity and chelation therapy.
AB  - PURPOSE: Common sources of lead exposure, the primary clinical effects of lead
      toxicity, and current recommendations for managing lead toxicity, including
      chelation therapy, are reviewed. SUMMARY: Common sources of lead exposure in
      children and adults include industrial and mining activities, paint, dust, soil,
      water, air, the workplace, food, trinkets, ethnic folk remedies, and cosmetics.
      The absorption and biological fate of lead are affected by a variety of factors,
      including an individual's nutritional status, health, and age. Children with a
      blood lead concentration of >10 microg/dL and adults with a blood lead
      concentration of > or = 45 mug/dL should undergo further evaluation. Symptoms and
      time to onset of symptoms postexposure may vary, and it can be difficult to
      identify the early, subtle neurologic effects of lead toxicity. The classic
      symptoms of lead toxicity generally correlate with blood lead concentrations of
      25-50 microg/dL in children and 40-60 microg/dL in adults. Management of lead
      toxicity requires extensive risk assessment and caregiver education. Chelation is
      generally not indicated for adults with blood lead concentrations of < 45
      microg/dL because of the potential risk of adverse drug events and concerns about
      remobilized lead, and chelation for children with blood lead concentrations of <
      45 microg/dL remains controversial. Dimercaprol, edetate calcium disodium, and
      succimer are the three agents primarily used for chelation. CONCLUSION: Lead
      toxicity remains a significant public health concern. Elimination of elevated
      blood lead levels in children can be accomplished by educating appropriate health
      care providers and caregivers, recognizing potential lead sources, and adopting
      aggressive prevention and case management measures.

PMID- 17189580
TI  - Meropenem -valproic acid interaction in patients with cefepime-associated status
      epilepticus.
AB  - PURPOSE: Two case reports of rapid decreases in valproic acid levels after
      initiation of meropenem in patients who developed new-onset seizure activity
      during treatment with cefepime are presented. SUMMARY: A 60-year-old Caucasian
      woman with myelodysplasia was transferred to the medical intensive care unit
      (MICU) on day 11 of her hospitalization. Cefepime was given as empiric therapy
      for febrile neutropenia. Pulmonary invasive aspergillosis was diagnosed. On day
      16 of hospitalization, epileptic activity was confirmed. Valproic acid was
      initiated. Cefepime was discontinued and meropenem was initiated for treatment of
      cefepime-resistant pneumonia. Serum valproic acid levels decreased to
      subtherapeutic levels within 24 hours. Meropenem was discontinued and ceftazidime
      was started on day 22; serum valproic acid levels gradually increased but never
      reached therapeutic levels again. The patient died of intractable invasive
      aspergillosis on day 33. A 54-year-old Caucasian man with myelodysplasia was
      admitted to the MICU for nonconvulsive status epilepticus. Ten days before
      admission, cefepime had been started empirically for the treatment of neutropenic
      fever. One day before MICU admission, valproic acid was initiated as treatment
      for status epilepticus. The next day, serum valproic acid levels were
      therapeutic; cefepime was switched to meropenem. Serum valproic acid levels
      decreased within 24 hours and phenytoin was added. On day 4, the patient's serum
      valproic acid levels decreased further and meropenem was discontinued. Although
      the valproic acid dosage was increased, valproic acid levels did not return to
      the therapeutic range. The patient died on day 11. CONCLUSION: Following cefepime
      therapy, a clinically important interaction between meropenem and valproic acid
      occurred in two critically ill patients with new-onset status epilepticus.

PMID- 17189581
TI  - Mild serotonin syndrome associated with concurrent linezolid and fluoxetine.
AB  - PURPOSE: A case of serotonin syndrome that developed during concurrent linezolid
      and fluoxetine is presented. SUMMARY: A 23-year-old white male patient was
      originally admitted to receive intravenous chemotherapy for acute myelogenous
      leukemia. He had a history of intravenous amphetamine abuse, hepatitis B virus
      infection, hepatitis C virus infection, depression, and bipolar disorder. The
      patient's routine medications before admission included methadone, fluoxetine,
      voriconazole, transdermal nicotine patch, lorazepam, and quetiapine. The patient
      developed persistent neutropenia and complications from chemotherapy, including
      mild mucositis. Despite treatment with levofloxacin, acyclovir, and voriconazole,
      the patient developed high fevers. Levofloxacin was discontinued and aztreonam
      and vancomycin were started. After a blood culture revealed that the bacteria
      were likely vancomycin resistant, vancomycin was discontinued and linezolid was
      initiated. Nine hours later, the patient began complaining of severe pain in his
      abdomen. After a total of four doses of linezolid, the patient reported further
      discomfort. Two days after linezolid initiation, a health care team member
      identified the interaction between fluoxetine and linezolid as the cause of the
      patient's symptoms, and linezolid was discontinued. All symptoms resolved within
      48 hours. While resolution generally occurs within 24-48 hours after
      discontinuing the offending agent, the time to resolution may be delayed if the
      agent has a long half-life or active metabolites, in which case admission to an
      intensive care unit is recommended. Cyproheptadine and chlorpromazine may also be
      used to treat symptoms. CONCLUSION: Serotonin syndrome developed in a patient
      taking concurrent linezolid and fluoxetine.

PMID- 17189582
TI  - Documentation of pharmacists' interventions in an emergency department and
      associated cost avoidance.
AB  - PURPOSE: An analysis was conducted of pharmacist interventions and resuscitation
      experiences, including pharmacist participation in a hospital emergency
      department (ED), and the potential cost avoidance associated with the
      interventions made by the pharmacists. METHODS: All pharmacists working in the ED
      prospectively documented the pharmacist interventions that were accepted by
      physicians and nursing staff and entered into a spreadsheet on a weekly basis,
      between September 1, 2003, and December 31, 2003. Intervention categories
      included the provision of drug information; recommendations for dosage
      adjustment, formulary interchange, initiation of medications, alternative drug
      therapy, discontinuation of drug therapy, changes in medication therapy due to
      allergy notification, drug therapy duplication prevention, or changes in the
      route of drug administration; questions from nursing staff; order clarifications;
      drug compatibility issues; patient information; toxicology; and drug interaction
      identification. Intervention data were analyzed and the likelihood of harm was
      scored; interventions were classified and analyzed by calculating average cost,
      probability of harm, and potential cost avoidance. RESULTS: During the study,
      2150 pharmacist interventions were documented. Pharmacists participated in the
      care of 1042 patients triaged to the resuscitation area of the ED. Cost avoidance
      during the study was determined to be 1,029,776 dollars. CONCLUSION: The most
      commonly documented interventions made by pharmacists involved in the care of
      patients visiting the ED included provision of drug information, dosage
      adjustment recommendations, responses to questions from nursing staff, formulary
      interchanges, and suggestions regarding initiation of drug therapy. The potential
      cost avoidance attributable to the pharmacist interventions during the study
      period was over 1 million dollars.

PMID- 17189583
TI  - Hospitals' compliance with prophylaxis guidelines for venous thromboembolism.
AB  - PURPOSE: A study was conducted to evaluate compliance with the Sixth American
      College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy
      guidelines for the prevention of venous thromboembolism (VTE) in hospitals.
      METHODS: Using the HealthFacts database, hospitalized patients, age 40 years or
      more, with medical conditions at risk for VTE (surgical, trauma, and acute spinal
      injury patients) were identified. Hospital admissions on or after January 1,
      2001, and concluded by March 31, 2005, were included if they met any of the
      following conditions as defined in the ACCP Consensus Conference on
      Antithrombotic Therapy guidelines: patients at risk of VTE medical conditions,
      major orthopedic surgery, general surgery, gynecological surgery, urologic
      surgery, trauma, neurosurgery, and acute spinal cord injury. Hospitalizations
      were identified using the International Classification of Diseases, 9th Revision,
      Clinical Modification codes. The primary objective was to examine whether
      patients received one of the indicated anticoagulants at the proper dosage and
      during the relevant hospital days as determined in the ACCP guidelines. Rates of
      compliance were assessed, and the reasons for guideline noncompliance were also
      determined. RESULTS: The overall compliance rate with ACCP guidelines was 13.3%
      (ranging from 2.8% for neurosurgery to 52.4% for orthopedic surgery) in the
      123,304 hospital admissions that were reviewed. Only 15.3% of patients with at
      risk medical conditions received prophylaxis in accordance with ACCP guidelines.
      Potential reasons for guideline noncompliance among selected conditions included
      the omission of prophylaxis, inadequate prophylaxis duration, and the wrong type
      of anticoagulant. CONCLUSION: A retrospective study found low rates of compliance
      with guidelines for thromboprophylaxis.

PMID- 17189584
TI  - Clinical pharmacy cardiac risk service for managing patients with coronary artery
      disease in a health maintenance organization.
AB  - PURPOSE: A clinical pharmacy service for managing the treatment of coronary
      artery disease in a health maintenance organization is described. SUMMARY:
      Despite the proven benefits of aggressive risk factor modification for patients
      with coronary artery disease (CAD), there remains a treatment gap between
      consensus- and evidence-based recommendations and their application in patient
      care. In 1998, Kaiser Permanente of Colorado developed the Clinical Pharmacy
      Cardiac Risk Service (CPCRS) to focus on the long-term management of patients
      with CAD to improve clinical outcomes. The primary goals of the CPCRS are to
      increase the number of CAD patients on lipid-lowering therapy, manage medications
      shown to decrease the risk of future CAD-related events, assist in the monitoring
      and control of other diseases that increase cardiovascular risk, provide patient
      education and recommendations for nonpharmacologic therapy, and act as a CAD
      information resource for physicians and other health care providers. Using an
      electronic medical record and tracking database, the service works in close
      collaboration with primary care physicians, cardiologists, cardiac rehabilitation
      nurses, and other health care providers to reduce cardiac risk in the CAD
      population. Particular attention is given to dyslipidemia, blood pressure,
      diabetes mellitus, and tobacco cessation. Treatment with evidence-based regimens
      is initiated and adjusted as necessary. Over 11,000 patients are currently being
      followed by the CPCRS. CONCLUSION: A clinical pharmacy service in a large health
      maintenance organization provides cardiac risk reduction for patients with CAD
      and helps close treatment gaps that may exist for these patients.

PMID- 17189585
TI  - Provision of pain management by a pharmacist with prescribing authority.
AB  - PURPOSE: The clinical and financial outcomes of a pain clinic managed by a
      pharmacist with prescribing authority are described. SUMMARY: Pharmacist
      clinicians in a for-profit, integrated health system recently received permission
      to bill for their services in certain ambulatory clinics. A pharmacist clinician,
      who had an individual Drug Enforcement Administration number and whose services
      are billable under New Mexico law, was chosen to assume the medication management
      responsibilities in a clinic where 90% of the patient population is treated for
      chronic non-cancer-related pain. No additional personnel were needed, and no
      additional space was required, eliminating overhead for the space and utilities
      needed for operating a new clinic. With the ability to bill for the pharmacist
      clinician's services, a new model for justification of clinical pharmacy services
      was developed for the ambulatory care clinics. The revenue generated was tracked
      by a medical billing system, and clinical outcomes were tracked using the
      clinic's database for patients' individual visual analogue scale (VAS) pain
      scores. Between June 2004 and June 2005, an average of 18 patients were seen by
      the pharmacist clinician each day. The clinic generated 107,550 dollars of actual
      revenue and saved the health plan over 450,000 dollars. There was a consistent
      decrease in mean VAS pain scores with continued visits. CONCLUSION: Patients with
      chronic non-cancer-related pain were managed effectively by a pharmacist with
      prescribing authority and refill authorization in a pain management clinic. The
      favorable clinical outcomes, revenue generated, and cost savings achieved
      justified the pharmacist clinician's services in this health system.

PMID- 17189586
TI  - Effects of technological interventions on the safety of a medication-use system.
AB  - PURPOSE: A study was conducted to assess the effects and outcomes of implementing
      new technology into the medication-use process. METHODS: A pharmacy computer
      system, automated dispensing cabinets, and point-of-care products were
      implemented. The hypotheses of the study were that system errors in each phase of
      the medication-use process would decrease with the implementation of each
      technological application and that workload measures, such as staffing and
      inventory levels, would increase. Using a scripted questionnaire, interviews of
      participating staff (registered nurses, licensed practical nurses, nursing-unit
      clerks, pharmacists, pharmacy technicians, physicians, and physician assistants)
      were conducted to determine their impressions of the safety of the medication-use
      system before and after the implementation of technology. All hospitalwide errors
      were reported monthly between November 2002 and July 2005 by the number of errors
      per 1000 patient days and were categorized by error type. The accuracy of the
      medication administration record was examined; the pharmacy dispensing process
      was evaluated for accuracy, timeliness, and system changes; the accuracy of
      medication administration was observed; and staffing changes were also evaluated.
      RESULTS: Because of the technology implementation, the accuracy of patient
      identification was introduced, process changes and technological design
      identified potential failure modes in the medication administration process,
      inventory increased, turn-around time to process medication doses in the pharmacy
      decreased, accuracy of medication administration increased, and the staffing of
      nurses and pharmacists increased. CONCLUSION: Implementation of new technology
      into the medication management system standardized the medication administration
      processes, decreased turnaround time for processing medication orders, and
      increased accuracy of medication administration to patients.

PMID- 17189587
TI  - Treatment and control of blood pressure in patients with diabetes mellitus.
AB  - PURPOSE: A study was conducted to characterize the prevalence of hypertension in
      patients with diabetes mellitus and the percentage of patients with diabetes and
      hypertension who achieved a targeted blood pressure goal (<135/80 mm Hg).
      METHODS: A retrospective, cross-sectional study was conducted in an ambulatory
      care clinic. Eligible patients were those individuals being managed for type 2
      diabetes mellitus at least once each year for two consecutive years. Blood
      pressure measurements that were recorded in the medical chart or written
      diagnoses of hypertension were used to determine the presence of comorbid
      hypertension. Data were collected from the chart and electronic record using a
      standardized form. Clinic visits over the previous 12 months were reviewed to
      evaluate hypertension criteria. A blood pressure of > or = 135/80 mm Hg was used
      to define hypertension. RESULTS: A final sample of 362 patients with type 2
      diabetes mellitus was included in the study. Of these, 79% had concomitant
      diabetes and hypertension. Blood pressure was controlled in 175 of 270 (65%)
      patients. Patients who met the blood pressure goal tended to be older and weigh
      less than those who did not. The adjusted odds of achieving the blood pressure
      goal were 1.9 times higher in those patients who also achieved their low-density
      lipoprotein cholesterol goal. Most patients were on at least one antihypertensive
      agent; approximately 39% of the 89 patients treated with monotherapy were above
      the blood pressure goal. Combination therapy was used in 164 patients;
      approximately 32% of patients treated with combination therapy were above the
      blood pressure goal. CONCLUSION: Among ambulatory care patients with diabetes,
      79% also had hypertension. Hypertension was controlled in 65% of patients with
      that disorder.

PMID- 17189589
TI  - Establishing a pharmaceutical care clinic in a Saudi Arabian health center.

PMID- 17189588
TI  - Reimbursement for clinical services provided by pharmacists: what are we doing
      wrong?

PMID- 17189590
TI  - Risk of lung cancer from residential heating and cooking fuels in Montreal,
      Canada.
AB  - Among the major sources of indoor air pollution are combustion by-products from
      heating and cooking. Concern is increasing that use of polluting heating and
      cooking sources can increase cancer risk. In Canada, most cooking and heating
      currently relies on electricity or natural gas, but, in the past, and still in
      some areas, coal and wood stoves were used for heating and gas and wood for
      cooking. In the course of a case-control study of lung cancer carried out in
      Montreal in 1996-2001, the authors collected information on subjects' lifetime
      exposure to such sources of domestic pollution by means of a personal interview
      with the subject or a next-of-kin proxy. Questionnaires were completed for 739
      male cases, 925 male controls, 466 female cases, and 616 female controls. Odds
      ratios were computed in relation to a few indices of exposure to traditional
      heating and cooking sources, adjusting for a number of covariates, including
      smoking. Among men, there was no indication of excess risks. Among women, the
      odds ratio for those exposed to both traditional heating and cooking sources was
      2.5 (95% confidence interval: 1.5, 3.6; n = 253). The findings for women suggest
      the need for research dedicated to exploring this association, with particular
      emphasis on improved exposure assessment.

PMID- 17189591
TI  - The impact of birth weight on infectious disease hospitalization in childhood.
AB  - Low birth weight, a result of preterm birth or intrauterine growth restriction,
      is a well-established indicator of survival in childhood. However, corresponding
      epidemiologic studies of the association between low birth weight and morbidity
      from infections throughout childhood are sparse. The authors evaluated the
      relation between birth weight and infectious diseases throughout childhood in a
      population-based cohort study comprising all children born in Denmark from 1977
      through 2004 (n = 1.7 million). Information on birth weight, gestational age, and
      potential confounding variables was linked to the children in the cohort,
      together with information on hospitalization with infectious disease. Poisson
      regression yielded rate ratios of hospitalization according to birth weight. The
      authors found that birth weight was inversely associated with risk of infectious
      disease hospitalization; among children aged 0-14 years, the risk of
      hospitalization increased 9% for each 500-g reduction in birth weight (increase
      in rate ratio = 1.09, 95% confidence interval: 1.09, 1.11). The effect was found
      to peak in infancy and to persist until 10 years of age. It was present also in
      children born at term (37-41 weeks of gestation). The present study is the first
      to demonstrate the measurable impact of birth weight on infectious diseases
      throughout childhood.

PMID- 17189592
TI  - IL-4Ralpha polymorphism in regulation of IL-4 synthesis by T cells: implication
      in susceptibility to a subset of murine lupus.
AB  - To thoroughly understand the role of IL-4 in the pathogenesis of systemic lupus
      erythematosus (SLE), a prototypic antibody-mediated systemic autoimmune disease,
      we examined the potential of in vitro IL-4 production by anti-CD3 mAb-stimulated
      splenic T cells in SLE model of NZB, BXSB and related mouse strains.
      Unexpectedly, both SLE-prone NZB and BXSB mice had a limited potential to produce
      IL-4, while disease-free NZW mice had a high potential. Levels in (NZB x NZW) F1
      and (NZW x BXSB) F1 were in between. Genome-wide search for quantitative trait
      loci (QTL) controlling this variation identified a single significant QTL in the
      vicinity of IL-4Ralpha gene on chromosome 7. Sequence analysis of IL-4Ralpha cDNA
      revealed that there are 17 nucleotide substitutions resulting in eight amino acid
      changes between NZB and NZW strains. BXSB showed the identical sequence, as did
      NZB. Thus, it was suggested that the NZW-type polymorphism controls a high
      potential and the NZB/BXSB-type polymorphism controls a low potential for IL-4
      production by T cells. Linkage studies using NZW x (NZW x BXSB) F1 male and (NZB
      x NZW) F1 x NZW female back-cross mice revealed that the BXSB/NZB-type IL-4Ralpha
      polymorphism significantly linked to BXSB, but not to (NZB x NZW) F1 lupus. Thus,
      the low IL-4-producing phenotype appears to predispose to SLE in BXSB, but not
      NZB-related strains, suggesting that the role of IL-4 in the pathogenesis may
      differ between certain subsets of SLE, even if they show similar disease
      phenotypes.

PMID- 17189594
TI  - Monitoring and screening plant populations with combined thermal and chlorophyll
      fluorescence imaging.
AB  - Thermal and chlorophyll fluorescence imaging are powerful tools for the study of
      spatial and temporal heterogeneity of leaf transpiration and photosynthetic
      performance. The relative advantages and disadvantages of these techniques are
      discussed. When combined, they can highlight pre-symptomatic responses not yet
      apparent in visual spectrum images and provide specific signatures for diagnosis
      of distinct diseases and abiotic stresses. In addition, their use for diagnosis
      and for selection for stomatal or photosynthetic mutants, these techniques can be
      applied for stress tolerance screening. For example, rapid screening for stomatal
      responses can be achieved by thermal imaging, while, combined with fluorescence
      imaging to study photosynthesis, they can potentially be used to derive leaf
      water use efficiency as a screening parameter. A particular advantage of imaging
      is that it allows continuous automated monitoring of dynamic spatial variation.
      Examples of applications include the study of growth and development of plant
      lines differing in stress resistance, yield, circadian clock-controlled
      responses, and the possible interactions between these parameters. In the future,
      such dual-imaging systems could be extended with complementary techniques such as
      hyperspectral and blue-green fluorescence imaging. This would result in an
      increased number of quantified parameters which will increase the power of stress
      diagnosis and the potential for screening of stress-tolerant genotypes.

PMID- 17189593
TI  - Th1 cell adjuvant therapy combined with tumor vaccination: a novel strategy for
      promoting CTL responses while avoiding the accumulation of Tregs.
AB  - We have previously described a method for adoptive immunotherapy of cancer based
      on antigen-specific T(h)1 cells. However, efficient induction of anti-tumor
      responses using T(h)1 cells remains a formidable challenge, especially for MHC
      class II-negative tumors. In the present study, we sought to develop a novel
      strategy to eradicate established tumors of the MHC class II-negative, ovalbumin
      (OVA)-expressing EG-7 cells. Tumor-bearing mice were intradermally treated with
      OVA-specific T(h)1 cells, combined with the model tumor antigen (OVA), near the
      tumor-draining lymph node (DLN). We found that tumor growth was significantly
      inhibited by this strategy and approximately 50-60% of tumor-bearing mice were
      completely cured. Tumor eradication was crucially dependent on the generation of
      OVA/H-2K(b)-specific CTLs in the tumor DLNs and tumor site. The injected T(h)1
      cells were mainly distributed in tumor DLNs, where they vigorously proliferated
      and enhanced the activation of dendritic cells. Strikingly, we also found that
      the accumulation of CD4(+)CD25(+) regulatory T cells (Tregs) was significantly
      inhibited in tumor DLNs by T(h)1 cell adjuvant therapy and this abrogation was
      associated with IFNgamma secreted by T(h)1 cells. These results identify T(h)1
      cell adjuvant therapy combined with tumor vaccination as a novel approach to the
      treatment of human cancer.

PMID- 17189595
TI  - Synthesis, transport and accumulation of quinolizidine alkaloids in Lupinus albus
      L. and L. angustifolius L.
AB  - Each of the principal quinolizidine alkaloids (QA) found in both xylem and phloem
      exudates together with extracts from all component organs collected from bitter
      (cv. Lupini) and sweet (cv. Ultra) cultivars of Lupinus albus L. were quantified
      by gas chromatographic analyses throughout reproductive development. In addition
      to establishing the major translocated QA species estimates for fluxes of QA to
      developing fruits based on their sap composition and water economy showed that
      around half of the QA that accumulated in fruit tissues was due to synthesis in
      situ and half to translocation principally by phloem. Detailed analyses of QA in
      transport fluids and component organs were extended to reciprocal homo- and
      hetero-grafts using bitter (cv. Fest) and sweet (cv. Danja) cultivars of L.
      angustifolius L. These data confirmed that the majority of QA were synthesized in
      shoot tissues. In both lupin species feeding and analysis of deuterated QA
      (lupanine and 13-hydroxylupanine) were used as tracers to demonstrate direct
      redistribution of alkaloids by translocation from mature leaves in phloem.

PMID- 17189596
TI  - Identification of differentially expressed genes in Malus domestica after
      application of the non-pathogenic bacterium Pseudomonas fluorescens Bk3 to the
      phyllosphere.
AB  - Biological control of plant diseases by the application of antagonistic micro
      organisms to the plant phyllosphere is only marginally understood. Suppression
      subtractive hybridization (SSH) was used for the identification of genes
      expressed after application of the non-pathogenic bacterium Pseudomonas
      fluorescens Bk3 to the phyllosphere of the apple scab-susceptible cultivar Malus
      domestica cv. Holsteiner Cox. In total, 157 expressed sequence tag (EST) clones
      were obtained. The sequencing of 113 ESTs which have a significantly elevated
      transcript level and the comparison of the obtained sequences with databases
      revealed similarities to different classes of pathogenesis-related proteins, for
      example, RNase-like PR10 protein and endochitinase, or similarities to proteins
      expressed under stress conditions that could have a protective function, for
      example, a germin-like protein, glutathione S-transferase, thioredoxin-like
      proteins, and heat shock proteins. In addition, several transcripts were
      identified that code for proteins which have a crucial role at different stages
      of pathogen recognition and in signalling pathways or an as yet unknown function
      in plant defence. The results show that a number of transcripts encoding
      proteins/enzymes which are known to be up-regulated after pathogen infection are
      also up-regulated after the application of a non-pathogenic bacterium to a M.
      domestica cultivar. The expression of these proteins might increase the plant
      resistance towards pathogen infection and damage.

PMID- 17189597
TI  - Evolution and differentiation of MSHR gene in different species.
AB  - Coat color offers some prospects for evolutionary studies due to its large amount
      of presumably adaptive coat color variation and conserved genetic mechanisms of
      generating different coat colors in different species. Melanocyte-stimulating
      hormone receptor (MSHR) gene is responsible for intraspecific and interspecific
      color variation in mammals and birds. A total number of 206 MSHR gene sequences
      belonging to 84 species, 58 genera, and 20 families were analyzed to investigate
      its evolution and differentiation in different species. Most of the species have
      954 bp and stop codon TGA. Species in Callithrix and Callimico have a stop codon
      mutation from TGA to TGG and elongate 81 bp with TAG as stop codon. Species in
      Phasianidae, Fringillidae, and Lemuridae also use TAG as stop codon. The Sus
      scrofa had an insertion of AACCAGACC encoding Asn-Gln-Thr from 85 to 93 bp. In
      Bovidae, a brown strain of cow with 966 bp due to the 12-bp duplication of
      GGCATTGCCCGG from 670 to 681 bp encoding for Gly-Ile-Ala-Arg was found. Teiidae
      has the smallest number of total mutations (6), silent mutations (3),
      nonsynonymous mutations (3), average number of nucleotide differences (1.519),
      synonymous nucleotide diversity (pi(s) = 0.0030), and nonsynonymous nucleotide
      diversity (pi(a) = 0.0029), and Hominidae, Lemuridae, Canidae, and Teiidae have
      higher ratio of pi(a)/pi(s) (0.537-0.973). The reconstructed phylogenetic tree of
      MSHR gene of families is basically consistent with the taxonomy of National
      Center for Biotechnology Information.

PMID- 17189598
TI  - Risk factors associated with the salmonella status of dairy farms in England and
      Wales.
AB  - Between October 1999 and February 2001 the salmonella status of 449 dairy farms
      in England and Wales was determined by environmental sampling on up to four
      occasions. Data were collected through interview-based questionnaires, and
      multivariable analyses were used to identify risk factors associated with the
      farms either being Salmonella positive (prevalence data) or becoming Salmonella
      positive (incidence data). Region, herd size, month of visit and the lack of a
      clean visitor parking area were significantly associated with the prevalence of
      Salmonella species, and there was a significant trend towards an increased risk
      in late summer and autumn. The introduction of six- to 24-month-old cattle into a
      herd was associated with a reduced prevalence, but the introduction of adult
      cattle only, or calves with other cattle, was associated with an increased (but
      not significant) risk of farms being Salmonella positive. Month of visit, the
      lack of a clean visitor parking area, the use of part-time workers and not
      feeding calves whole milk, but not region or herd size, were associated with an
      increased incidence of salmonella.

PMID- 17189600
TI  - Effect of bovine lactoferrin on the immune responses of captive bottlenosed
      dolphins (Tursiops truncatus) being transported over long distances.
AB  - Bovine lactoferrin was administered orally, in feed, to six bottlenosed dolphins
      (Tursiops truncatus) before they were transported for approximately six hours;
      their stress responses were compared with those of five untreated dolphins.
      During the journey the dolphins had an increased plasma concentration of
      cortisol, and lymphopenia, eosinopenia and mild neutrophilia, indicating a stress
      response. The administration of lactoferrin did not affect the function of the
      dolphins' polymorphonuclear leucocytes, but affected their leucogram by
      maintaining the number of circulating eosinophils.

PMID- 17189599
TI  - Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy.
AB  - Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally
      with gabapentin for a minimum of three months at an initial dose of 10 mg/kg
      every eight hours. They were all experiencing episodes of generalised tonic
      clonic seizures and had been treated chronically with a combination of
      phenobarbital and potassium bromide at doses sufficient to reach acceptable
      therapeutic serum levels without causing significant side effects. In each dog,
      the number of seizures per week, the average duration of the seizures and the
      number of days on which seizures occurred were compared for the three months
      before and after they were treated with gabapentin. A minimum 50 per cent
      reduction in the number of seizures per week was interpreted as a positive
      response to gabapentin, and six of the dogs showed a positive response. After the
      addition of gabapentin, both the number of seizures per week (P= 0.005) and the
      number of days with any seizures in a one-week period (P=0.03) were significantly
      reduced. Mild side effects of ataxia and sedation were observed in five of the
      dogs, but they were not severe enough to warrant the treatment being discontinued
      during the trial.

PMID- 17189601
TI  - Vacuolar lesion profile of BSE in the Republic of Ireland.

PMID- 17189602
TI  - Auricular chondropathy in two Swiss Braunvieh heifers.

PMID- 17189604
TI  - Canine parvovirus vaccination.

PMID- 17189605
TI  - West Nile virus in horses.

PMID- 17189606
TI  - Latrines for cattle?

PMID- 17189608
TI  - Evolutionarily new sequences expressed in tumors.
AB  - BACKGROUND: Earlier we suggested the concept of the positive evolutionary role of
      tumors. According to this concept, tumors provide conditions for the expression
      of evolutionarily new and/or sleeping genes in their cells. Thus, tumors are
      considered as evolutionary proving ground or reservoir of expression. To support
      this concept we have previously characterized in silico and experimentally a new
      class of human tumor-related transcribed sequences. RESULTS: In this article we
      describe results of further studies of previously described tumor-related
      sequences. The results of molecular phylogeny studies, Southern hybridization
      experiments and computational comparison with genomes of other species are
      presented. CONCLUSION: These results suggest that these previously described
      tumor-related human transcripts are also relatively evolutionarily new.

PMID- 17189607
TI  - Effects of lipoprotein lipase and statins on cholesterol uptake into heart and
      skeletal muscle.
AB  - Regulation of cholesterol metabolism in cultured cells and in the liver is
      dependent on actions of the LDL receptor. However, nonhepatic tissues have
      multiple pathways of cholesterol uptake. One possible pathway is mediated by LPL,
      an enzyme that primarily hydrolyzes plasma triglyceride into fatty acids. In this
      study, LDL uptake and tissue cholesterol levels in heart and skeletal muscle of
      wild-type and transgenic mice with alterations in LPL expression were assessed.
      Overexpression of a myocyte-anchored form of LPL in heart muscle led to increased
      uptake of LDL and greater heart cholesterol levels. Loss of LDL receptors did not
      alter LDL uptake into heart or skeletal muscle. To induce LDL receptors, mice
      were treated with simvastatin. Statin treatment increased LDL receptor expression
      and LDL uptake by liver and skeletal muscle but not heart muscle. Plasma
      creatinine phosphokinase as well as muscle mitochondria, cholesterol, and lipid
      droplet levels were increased in statin-treated mice overexpressing LPL in
      skeletal muscle. Thus, pathways affecting cholesterol balance in heart and
      skeletal muscle differ.

PMID- 17189610
TI  - Variable fluorescence in green sulfur bacteria.
AB  - Green sulfur bacteria possess a complex photosynthetic machinery. The dominant
      light harvesting systems are chlorosomes, which consist of bacteriochlorophyll c,
      d or e oligomers with small amounts of protein. The chlorosomes are energetically
      coupled to the membrane-embedded iron sulfur-type reaction center via a
      bacteriochlorophyll a-containing baseplate protein and the Fenna-Matthews-Olson
      (FMO) antenna protein. The fluorescence yield and spectral properties of these
      photosynthetic complexes were investigated in intact cells of several species of
      green sulfur bacteria under physiological, anaerobic conditions. Surprisingly,
      green sulfur bacteria show a complex modulation of fluorescence yield upon
      illumination that is very similar to that observed in oxygenic phototrophs.
      Within a few seconds of illumination, the fluorescence reaches a maximum, which
      decreases within a minute of illumination to a lower steady state. Fluorescence
      spectroscopy reveals that the fluorescence yield during both processes is
      primarily modulated on the FMO-protein level, while the emission from chlorosomes
      remains mostly unchanged. The two most likely candidates that modulate
      bacteriochlorophyll fluorescence are (1) direct excitation quenching at the FMO
      protein level and (2) indirect modulation of FMO-protein fluorescence by the
      reduction state of electron carriers that are part of the reaction center.

PMID- 17189609
TI  - Amygdala size in amyotrophic lateral sclerosis without dementia: an in vivo study
      using MRI volumetry.
AB  - BACKGROUND: Evidence for extra-motor involvement in non-demented patients with
      amyotrophic lateral sclerosis (ALS) has been provided by multiple studies, in
      particular neuropathological studies have demonstrated neuronal loss in the
      amygdala. The aim of this study was to investigate possible alterations of
      amygdala volumes in vivo. METHODS: Twenty-two moderately disabled patients with
      definite ALS without cognitive or behavioural deficits and 22 age-matched healthy
      controls were included. Amygdala and total brain volumes were measured by region
      of-interest-based volumetry in 3-D MRI. RESULTS: A trend was observed with
      reduced amygdala size in the ALS group, since mean absolute and brain size
      corrected amygdala volumes were 6.9% and 7.6% lower in the patient group compared
      to those in normal controls (P = 0.086 and P = 0.110), respectively. CONCLUSION:
      Volumetrically identifiable alterations of the amygdala can be mapped in vivo and
      may be associated with psychopathological findings in later stages of ALS.

PMID- 17189611
TI  - Preservation of microorganisms as deposits for patent application.

PMID- 17189612
TI  - A role for galectin-3 in CD13-mediated homotypic aggregation of monocytes.
AB  - We recently reported that anti-CD13 mAbs induce homotypic aggregation of
      monocytic cells. This phenomenon is signal transduction dependent and does not
      require CD13 aminopeptidase activity. Since CD13 is heavily glycosylated and a
      member of the galectin family (galectin-4) has been shown to associate with CD13
      in the intestinal epithelium, we hypothesized that CD13-mediated aggregation
      might proceed through a carbohydrate-dependent mechanism involving galectin-3,
      the most highly expressed galectin on monocytes. We report here that lactose and
      anti-galectin-3 antibodies completely abrogate homotypic aggregation induced by
      anti-CD13 antibodies. Furthermore, galectin-3 co-immunoprecipitates with CD13
      from resting U-937 cells and this association decreases during the aggregation
      process, a phenomenon that may have functional implications. Together, the
      results presented here point to a key role for galectin-3 in CD13-mediated
      homotypic aggregation of monocytic cells.

PMID- 17189613
TI  - Apo calmodulin binding to the L-type voltage-gated calcium channel Cav1.2 IQ
      peptide.
AB  - The influx of calcium through the L-type voltage-gated calcium channels (LTCCs)
      is the trigger for the process of calcium-induced calcium release (CICR) from the
      sarcoplasmic reticulum, an essential step for cardiac contraction. There are two
      feedback mechanisms that regulate LTCC activity: calcium-dependent inactivation
      (CDI) and calcium-dependent facilitation (CDF), both of which are mediated by
      calmodulin (CaM) binding. The IQ domain (aa 1645-1668) housed within the
      cytoplasmic domain of the LTCC Cav1.2 subunit has been shown to bind both calcium
      loaded (Ca2+CaM ) and calcium-free CaM (apoCaM). Here, we provide new data for
      the structural basis for the interaction of apoCaM with the IQ peptide using NMR,
      revealing that the apoCaM C-lobe residues are most significantly perturbed upon
      complex formation. In addition, we have employed transmission electron microscopy
      of purified LTCC complexes which shows that both apoCaM and Ca2+CaM can bind to
      the intact channel.

PMID- 17189614
TI  - Bone morphogenetic protein-4 abrogates lumen formation by mammary epithelial
      cells and promotes invasive growth.
AB  - Bone morphogenetic proteins (BMPs) are multifunctional cytokines that regulate
      key developmental processes, but are also overexpressed in many carcinomas. To
      assess whether BMPs would influence the three-dimensional architecture of
      epithelial structures, we took advantage of an in vitro model in which mammary
      epithelial cells form alveolar-like spherical cysts in collagen gels. We found
      that BMP-4 has a dramatic, biphasic effect on the organization of epithelial
      cysts. When added in the concentration range of 1-10 ng/ml, the cytokine
      abrogates lumen formation and induces the outgrowth of multiple invasive cord
      like structures. At higher concentrations (20-100 ng/ml), BMP-4 additionally
      disrupts cell-cell adhesion, resulting in cyst disintegration and scattering of
      individual cells into the surrounding collagen matrix. The finding that BMP-4
      subverts the ability of mammary epithelial cells to form polarized lumen
      containing structures and endows them with invasive properties supports the
      involvement of this cytokine in the progression of breast cancer.

PMID- 17189615
TI  - Assemblages of simian virus 40 capsid proteins and viral DNA visualized by
      electron microscopy.
AB  - SV40 assembles in the nucleus by addition of capsid proteins to the
      minichromosome. The VP15VP2/3 capsomer is composed of a pentamer of the major
      protein VP1 complexed with a monomer of a minor protein, VP2 or VP3. In the
      capsid, the capsomers are bound together via their flexible carboxy-terminal
      arms. Our previous studies suggested that the capsomers are recruited to the
      packaging signal ses via avid interaction with Sp1. During assembly Sp1 is
      displaced, allowing chromatin compaction. Here we investigated the interactions
      in vitro of VP1(5)VP2/3 capsomers with the entire SV40 genome, using mutant VP1
      deleted in the carboxy-arm that cannot assemble, but retains DNA-binding
      capacity. EM revealed that VP1(5)VP2/3 complexes bind non-specifically at random
      locations around the DNA. Sp1 was absent from mature virions. The findings
      suggest that multiple capsomers attach simultaneously to the viral genome,
      increasing their local concentration, facilitating rapid, concerted assembly
      reaction and removal of Sp1.

PMID- 17189616
TI  - Musclin gene expression is strongly related to fast-glycolytic phenotype.
AB  - Musclin has been described as a muscle-derived secretory peptide, responsive to
      insulin in vivo, and inducing insulin resistance in vitro. Because muscle fibers
      display very different metabolic properties and insulin sensitivity, we tested
      the hypothesis that musclin expression could depend on myofiber type. Musclin
      mRNA was detected at high level in fast gastrocnemius and plantaris muscles, but
      only as traces in soleus, a slow-twitch muscle. A single fiber analysis showed
      that musclin was produced by muscle fibers themselves, almost exclusively type
      IIb fibers. Slow to fast transition of soleus phenotype after hindlimb suspension
      increased musclin mRNA levels, whereas fast to slow transition of plantaris
      phenotype after functional overload decreased musclin mRNA levels. This clearly
      suggests that musclin transcription is strongly related to fast-glycolytic
      phenotype. We conclude that musclin is produced by myocytes in a highly fiber
      type specific manner and that physiological changes in type IIb MHC lead to
      coordinated musclin expression.

PMID- 17189617
TI  - Accumulation of liposome with Sialyl Lewis X to inflammation and tumor region:
      application to in vivo bio-imaging.
AB  - We prepared the liposome binding Sialyl Lewis X (SLX) on the surface in order to
      specifically and efficiently deliver substances (fluorescent materials, chemical
      substances, proteins, genes, etc.) to inflammation or tumor regions. The liposome
      with SLX (SLX-Lipo-Cy5.5), in which fluorescent substance Cy5.5 was included, was
      administered intravenously to arthritis or Ehrlich Ascites Tumor (EAT) bearing
      mouse, and the accumulation of liposome was observed using two types of in vivo
      fluorescent imaging equipment. The result was that the accumulation of SLX-Lipo
      Cy5.5 to inflammation or tumor regions was significantly higher than the control
      liposome without sugar chain (Lipo-Cy5.5) at 24 and 48 h after administration. In
      addition, it was confirmed that this accumulation showed a shift of liposome from
      blood vessels to the surrounding tissues. Thus, it was proven that this liposome
      is useful not only as an in vivo bio-imaging reagent but also as a drug delivery
      system (DDS).

PMID- 17189618
TI  - Vascular endothelial growth factor promotes brain tissue regeneration with a
      novel biomaterial polydimethylsiloxane-tetraethoxysilane.
AB  - In the brain after infarction or trauma, the tissue eventually becomes
      pannecrotic and forms a cavity. In such situations, a scaffold is necessary for
      the implanted or migrated cells to produce new tissue. In this present study,
      therefore, we attempted to restore brain tissue using a novel biomaterial,
      polydimethylsiloxane-tetraethoxysilane (PDMS-TEOS) hybrid with or without
      vascular endothelial growth factor (VEGF), which is crucial for new vessel
      formation. When PDMS-TEOS scaffold was implanted into the artificial brain
      defect, it remained at the implanted site and kept the integrity of the brain
      shape. At 30 days after the implantation, the marginal territory of PDMS-TEOS
      scaffold became occupied by newly formed tissue. Immunohistochemical analysis
      revealed that the new tissue was constituted by astrocytes and endothelial cells.
      Addition of VEGF increased the newly produced tissue volume, and the
      immunohistochemical analysis showed that the numbers of astrocytes and
      endothelial cells were increased. Double staining with proliferation maker Ki67
      demonstrated that VEGF significantly increased newly formed astrocytes and
      endothelial cells, indicating that addition of VEGF accelerated tissue
      restoration and angiogenesis. These findings show that implantation of PDMS-TEOS
      scaffold with VEGF might be effective for treating old brain infarction or
      trauma.

PMID- 17189620
TI  - Comparative aspects of p73 and Reelin expression in Cajal-Retzius cells and the
      cortical hem in lizard, mouse and human.
AB  - Cajal-Retzius (CR) cells of the mammalian neocortex co-express the extracellular
      matrix protein Reelin and p73, a transcription factor involved in cell death and
      survival. Most neocortical CR cells derive from the cortical hem, with minor
      additional sources. We analyzed the distribution of Reelin and p73 immunoreactive
      (ir) neurons in the telencephalon of Lacerta galloti from early embryonic stages
      to hatching. Numerous Reelin-ir cells appeared in the pallial MZ from the
      preplate stage onward. Conversely, p73-ir cells were rare in the pallial preplate
      and not observed in the cortical plate. Subpallial p73-ir cells spread from the
      septum and the telencephalic-diencephalic boundary to the pial surface of the
      basal forebrain and amygdala, respectively, where they co-expressed Reelin and
      p73. A small group of Reelin/p73-ir CR cells appeared in a rudimentary cortical
      hem at the interface of the medial cortex and choroid plexus. Comparison with
      early embryonic stages of mice and humans showed similar foci of p73-ir cells in
      the septum and at the telencephalic-diencephalic boundary and revealed an
      increasing prominence of the cortical hem, in parallel with increasing numbers of
      neocortical Reelin/p73 positive CR cells, which attain highest differentiation in
      the human brain. Our data show that Reelin-expression in the pallium is
      evolutionarily conserved and independent of a cortical hem, and suggest that p73
      in the cortical hem may be involved in the evolutionary increase in number and
      complexity of the mammalian neocortical CR cells.

PMID- 17189619
TI  - The role of the basal ganglia and cerebellum in language processing.
AB  - The roles of the cerebellum and basal ganglia have typically been confined in the
      literature to motor planning and control. However, mounting evidence suggests
      that these structures are involved in more cognitive domains such as language
      processing. In the current study, we looked at effective connectivity (the
      influence that one brain region has on another) of the cerebellum and basal
      ganglia with regions thought to be involved in phonological processing, i.e. left
      inferior frontal gyrus and left lateral temporal cortex. We analyzed functional
      magnetic resonance imaging data (fMRI) obtained during a rhyming judgment task in
      adults using dynamic causal modeling (DCM). The results showed that the
      cerebellum has reciprocal connections with both left inferior frontal gyrus and
      left lateral temporal cortex, whereas the putamen has unidirectional connections
      into these two brain regions. Furthermore, the connections between cerebellum and
      these phonological processing areas were stronger than the connections between
      putamen and these areas. This pattern of results suggests that the putamen and
      cerebellum may have distinct roles in language processing. Based on research in
      the motor planning and control literature, we argue that the putamen engages in
      cortical initiation while the cerebellum amplifies and refines this signal to
      facilitate correct decision making.

PMID- 17189621
TI  - Chronic cocaine exposure in the SCID mouse model of HIV encephalitis.
AB  - Clinical and preclinical evidence suggests that cocaine exposure hastens
      progression of the HIV disease process. An established active, euphoric dose of
      cocaine (20 mg/kg) was administered to SCID mice according to a regimen
      consistent with exposure to the drug by cocaine-abusing HIV-infected patients to
      determine the effects of cocaine on four previously established pathological
      characteristics of HIV encephalitis: cognitive deficits, fatigue, astrogliosis,
      and microgliosis. Mice were intracranially inoculated with either HIV-infected,
      or uninfected macrophages and then injected with either cocaine or saline in a 2
      (Infection)x2 (Cocaine) factorial design. Cognition was assessed by acquisition
      and retention of a spatially cued learning task. Fatigue was assessed by
      monitoring motor activity following a 2 min forced swim. Mice were then
      sacrificed to determine the extent of astrogliosis and microgliosis in the four
      groups. Results indicated that in comparison to uninfected controls, HIV positive
      mice had increased astrogliosis and microgliosis, cognitive deficits, and
      recovered more slowly from fatigue. However, despite evidence that the cocaine
      exposure regimen activated the central nervous system and had long-term CNS
      effects, the drug did not alter the behavioral or the neuropathological deficits
      noted in HIV-infected SCID mice.

PMID- 17189623
TI  - Macrovascular disease in type 2 diabetes: We do need animal models for in vivo
      studies.

PMID- 17189622
TI  - The nitroxyl anion (HNO) is a potent dilator of rat coronary vasculature.
AB  - OBJECTIVE: The nitroxyl anion (HNO) is the one-electron reduction product of
      NO(). This redox variant has been shown to be endogenously produced and to have
      effects that are pharmacologically distinct from NO(). This study investigates
      the vasodilator and chronotropic effects of HNO in the rat isolated coronary
      vasculature. METHODS: Sprague-Dawley rat hearts were retrogradely perfused with
      Krebs' solution (8 ml/min) using the Langendorff technique. Perfusion pressure
      was raised using a combination of infusion of phenylephrine and bolus additions
      of the thromboxane mimetic U46619 to attain a baseline perfusion pressure of 100
      120 mm Hg. The vasodilator effects of a nitroxyl anion donor, Angeli's salt, were
      examined in the absence and presence of HNO and NO* scavengers, K+ channel
      inhibition, and soluble guanylate cyclase (sGC) inhibition. In addition, the
      inotropic and chronotropic effects of Angeli's salt were examined in hearts at
      resting perfusion pressure (50-60 mm Hg) and compared to responses evoked by
      acetylcholine and isoprenaline. RESULTS: Angeli's salt causes a potent and
      reproducible vasodilatation in isolated perfused rat hearts. This response is
      unaffected by the NO* scavenger hydroxocobalamin (0.1 mM) but is significantly
      inhibited by the HNO scavenger N-acetyl-L-cysteine (4 mM), suggesting that HNO is
      the mediator of the observed responses. Vasodilatation responses to Angeli's salt
      were virtually abolished in the presence of the sGC inhibitor ODQ (10 microM).
      The magnitude of the vasodilatation response to Angeli's salt was significantly
      reduced in the presence of 30 mM K+, 10 microM glibenclamide and in the presence
      of the calcitonin gene-related peptide (CGRP) antagonist CGRP((8-37)) (0.1
      microM). Angeli's salt had little effect on heart rate or force of contraction,
      whilst isoprenaline and acetylcholine elicited significant positive and negative
      cardiotropic effects, respectively. CONCLUSIONS: The HNO donor Angeli's salt
      elicits a potent and reproducible vasodilatation response. The results suggest
      that the response is elicited by HNO through sGC-mediated CGRP release and K(ATP)
      channel activation.

PMID- 17189625
TI  - Supercooling ability is surprisingly invariable in eggs of the land snail
      Cantareus aspersus.
AB  - From an ontogenetic point of view, invertebrate eggs are generally the most
      freezing intolerant stage of a species. Development state, water content and
      acclimation may affect their supercooling ability. In this study, we measured
      fresh mass, water content and temperature of crystallisation (T(c)) of eggs of
      the edible land snail Cantareus aspersus, depending on its form ("aspersa"vs.
      "maxima"), incubation temperature (20, 12 and 7 degrees C) and physiological age
      (as part of the complete development). We also tested their tolerance to
      freezing. Despite a high number of individual observations (n=759) and
      significant differences of fresh mass and water content between both subspecies,
      no effect of origin, incubation temperature or development state has been found
      in this study. T(c) remained constant whatever the condition, with an overall
      mean of -5.40+/-0.24 degrees C (mean+/-SD). We suggest that fresh mass is
      important, a high water content and a constantly wet surface confer to land snail
      eggs a poor ability to supercool. Moreover, the presence of ice nucleating agents
      at the egg surface (microorganisms present in the soil, calcium carbonate
      crystals of the egg shell) might induce freezing. Thus, considering the present
      results, to delay hatching by cryopreservation of eggs does not seem possible.

PMID- 17189624
TI  - Establishment of a sandwich ELISA using commercial antibody for plasma or serum 3
      nitrotyrosine (3NT). Elevation in inflammatory diseases and complementary between
      3NT and myeloperoxidase.
AB  - BACKGROUND: Amino acid tyrosine residue of a protein can be nitrated to form 3
      nitrotyrosine (3NT), which is now being considered as a marker of inflammation,
      oxidative and nitrosative stress. METHOD: An in-house ELISA has been established
      using the same commercial antibody for both binding and detection of 3NT
      containing proteins. RESULTS: The sensitivity of the in-house ELISA was 1.8
      nmol/l. The imprecision was <10% at all concentrations. The in-house assay
      correlates well with a commercial kit (r=0.89). In addition to EDTA plasma, we
      found that both heparinized plasma and serum can also be used to quantify 3NT
      concentration. Using the in-house ELISA we have detected increased concentrations
      of 3NT in diseases known to be associated with inflammation and also in subjects
      with polyps. As marker of oxidative stress and inflammation, both 3NT and
      myeloperoxidase are complementary to each other in test sensitivity. CONCLUSION:
      This ELISA can be used in the clinical laboratories to monitor the inflammatory
      disease activity and assess early risks that are associated with inflammation,
      oxidative and nitrosative stress.

PMID- 17189626
TI  - Functions of a jumonji-cyclin D1 pathway in the coordination of cell cycle exit
      and migration during neurogenesis in the mouse hindbrain.
AB  - During development of the mouse central nervous system (CNS), most neural
      progenitor cells proliferate in the ventricular zone (VZ). In many regions of the
      CNS, neural progenitor cells give rise to postmitotic neurons that initiate
      neuronal differentiation and migrate out of the VZ to the mantle zone (MZ).
      Thereafter, they remain in a quiescent state. Here, we found many ectopic mitotic
      cells and cell clusters expressing neural progenitor or proneural marker genes in
      the MZ of the hindbrain of jumonji (jmj) mutant embryos. When we examined the
      expression of cyclin D1, which is repressed by jmj in the repression of cardiac
      myocyte proliferation, we found many ectopic clusters expressing both cyclin D1
      and Musashi 1 in the MZ of mutant embryos. jmj is mainly expressed in the cyclin
      D1 negative region in the hindbrain, and cyclin D1 expression in the VZ was
      upregulated in jmj mutant mice. In jmj and cyclin D1 double mutant mice, the
      ectopic mitosis and formation of the abnormal clusters in the MZ were rescued.
      These results suggest that a jmj-cyclin D1 pathway is required for the precise
      coordination of cell cycle exit and migration during neurogenesis in the mouse
      hindbrain.

PMID- 17189627
TI  - The myosin co-chaperone UNC-45 is required for skeletal and cardiac muscle
      function in zebrafish.
AB  - The assembly of myosin into higher order structures is dependent upon accessory
      factors that are often tissue-specific. UNC-45 acts as such a molecular chaperone
      for myosin in the nematode Caenorhabditis elegans, in both muscle and non-muscle
      contexts. Although vertebrates contain homologues of UNC-45, their requirement
      for muscle function has not been assayed. We identified a zebrafish gene, unc45b,
      similar to a mammalian unc-45 homologue, expressed exclusively in striated muscle
      tissue, including the somites, heart and craniofacial muscle. Morpholino
      oligonucleotide-mediated knockdown of unc45b results in paralysis and cardiac
      dysfunction. This paralysis is correlated with a loss of myosin filaments in the
      sarcomeres of the trunk muscle. Morphants lack circulation, heart looping and
      display severe cardiac and yolk-sac edema and also demonstrate ventral
      displacement of several jaw cartilages. Overall, this confirms a role for unc45b
      in zebrafish motility consistent with a function in myosin thick filament
      assembly and stability and uncovers novel roles for this gene in the function and
      morphogenesis of the developing heart and jaw. These results suggest that Unc45b
      acts as a chaperone that aids in the folding of myosin isoforms required for
      skeletal, cranial and cardiac muscle contraction.

PMID- 17189628
TI  - Sources of variability in levels and exposure to trihalomethanes.
AB  - In the framework of a cohort study of pregnant women conducted in Brittany
      (France), we assessed the exposure to trihalomethanes (THM) during pregnancy in a
      subset by evaluating (1) potential sources of variability in household THM
      levels; (2) the between- and within-subject variability in THM levels; (3) THM
      levels in swimming pools; and (4) the role of water-related habits on total THM
      uptake. We visited 109 women from the ongoing cohort study at home for an
      interview and collection of tap water from October to December 2004. Forty-three
      of them were re-contacted to obtain a second tap water sample in April-May 2005.
      We designed a questionnaire to collect individual information on source and
      amount of drinking water, frequency of showering, bathing, and swimming pool
      attendance, and household characteristics. We obtained 282 THM measurements, 152
      specifically for the study and 130 from a regulatory agency. Personal information
      and environmental data were combined using two methodologies (method 1 using
      regulatory data and method 2 using our THM measurements) with a different set of
      assumptions. We calculated ingestion, showering, bathing, and swimming pool THM
      uptakes and added up those uptakes to calculate total THM uptake. Average THM
      levels from our measurements in October, November-December, and April-May were
      61.3, 45.1, and 54.5 microg/l, respectively. Geographical variability was low and
      characteristics of the household did not influence THM levels. Within-subject
      variability in THM levels was three times higher than between-subject
      variability. Average THM level in swimming pools was 80.4 microg/l. Average water
      consumption during pregnancy was 1.9l/day. The source of the household drinking
      water was 90% bottled, 8% municipal, and 2% from other sources. Forty-seven per
      cent attended swimming pools during pregnancy. Using method 1, the geometric mean
      of total THM uptake was 0.93 microg/day. Showering contributed 64%, swimming in
      pools 23%, bathing 12%, and drinking water 1% to the total THM uptake. In a
      setting with low geographical variability and limited environmental measurements,
      individual data is highly relevant to determine personal THM exposure and uptake.
      In a population that mainly drinks bottled water (e.g., pregnant women),
      individual THM uptakes are dominated by inhalation and dermal absorption during,
      showering, swimming in pools, and bathing.

PMID- 17189630
TI  - Some statistical issues related to multiple linear regression modeling of beach
      bacteria concentrations.
AB  - As a fast and effective technique, the multiple linear regression (MLR) method
      has been widely used in modeling and prediction of beach bacteria concentrations.
      Among previous works on this subject, however, several issues were insufficiently
      or inconsistently addressed. Those issues include the value and use of
      interaction terms, the serial correlation, the criteria for model selection, and
      model assessment. The present work shows that serial correlations, as often
      present in sequentially observed data records, deserve full attention from the
      modeler. The testing and adjustment for the time-series effect should be
      implemented in a statistically rigorous framework. The R(2) and Cp-statistic as
      joint criteria are recommended for the model selection process, while using the t
      statistics associated with the full model is erroneous. During model selection,
      using interaction terms can often help to decrease the bias in reduced models,
      although the resulting improvement in the numerical performance may be limited.
      For the assessment of the model predictive capacity, which is different from
      testing the goodness of fit, a comprehensive set of statistics are advocated to
      allow for an objective evaluation of different models. Results obtained from the
      data at Huntington Beach, OH, show that erroneous conclusions could be drawn if
      only the model R(2) and the count of type I and type II errors are considered. In
      this sense, several previous works deserve further investigation.

PMID- 17189629
TI  - Serum PCBs, p,p'-DDE and HCB predict thyroid hormone levels in men.
AB  - Polychlorinated biphenyls (PCBs) and some organochlorine pesticides, which
      continue to be measurable in a high proportion of blood samples from the general
      population, have been found to alter thyroid hormone levels in animals and
      humans. However, studies of these relationships in adult men are limited and
      results across studies have been inconsistent. In the present study, we measured
      serum levels of 57 PCB congeners, dichlorodiphenyldichloroethylene (p,p(')-DDE, a
      stable metabolite of DDT), and hexachlorobenzene (HCB), as well as free T(4),
      total T(3), and TSH, in 341 adult men recruited from an infertility clinic from
      2000 to 2003. In multivariate linear regression, there were positive associations
      between p,p(')-DDE and both free T(4) and total T(3), and an inverse association
      between p,p(')-DDE and TSH. Conversely, for PCBs there was only a suggestive
      inverse association between PCB 153 and total T(3) when potential confounding
      variables were considered. However, when results were additionally adjusted for
      p,p(')-DDE, inverse associations with T(3) were significant for PCB 138, PCB 153,
      sum of PCBs and three different PCB groupings, and HCB, while the positive
      associations between p,p(')-DDE and T(3) also remained. In conclusion, serum
      concentrations of PCBs, p,p(')-DDE, and HCB were associated with circulating
      thyroid hormone levels in adult men. ABBREVIATIONS: BMI, body mass index; CYP,
      cytochrome P450; DDT, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; HCB,
      hexachlorobenzene; MDL, method detection limit; NHANES, national health and
      nutrition examination survey: p,p(')-DDE, 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene; PCB, polychlorinated biphenyl; T(3), triiodothyronine;
      T(4), thryoxine; TSH, thyroid stimulating hormone (thyrotrophin); US, United
      States.

PMID- 17189631
TI  - Assessment of hepatocellular damage and hematological alterations in mice
      chronically fed p-dimethyl aminoazobenzene and phenobarbital.
AB  - Two sets of mice (Mus musculus) were chronically fed 0.06% p
      dimethylaminoazobenzene (p-DAB) and 0.05% Phenobarbital (PB) for 90 and 120 days,
      respectively, and several cell biological and hematological parameters were
      studied against normal diet fed controls. The cell biological studies included:
      (i) matrix metalloproteinase (MMP) and reduced glutathione content (GSH), and
      (ii) ultra-structural changes in liver through scanning (SEM) and transmission
      (TEM) electron microscopies. Further, changes in some other parameters like blood
      glucose level, cholesterol and hemoglobin contents, serum cortisol concentration
      and rate of viability of lymphocytes were also recorded. The serum hormonal
      levels of estradiol and testosterone were also measured in view of the
      observation that mice subjected to chronic feeding of p-DAB and PB had
      dramatically reduced reproductive abilities. All results clearly indicated that
      the chronic feeding of the carcinogens induced considerable toxicity and palpable
      hepato-cellular injuries along with some other changes during the carcinogenetic
      process in liver.

PMID- 17189633
TI  - Schistosoma mansoni: the IMP4 gene is involved in DNA repair/tolerance after
      treatment with alkylating agent methyl methane sulfonate.
AB  - Using a functional complementation strategy, we have isolated a Schistosoma
      mansoni cDNA that complemented Escherichia coli mutant strains which are
      defective in the DNA base excision repair pathway. This cDNA partially
      complemented the MMS-sensitive phenotype of these strains. The sequence of the
      isolated cDNA was homologous to genes involved in the RNA metabolism pathway,
      especially ScIMP4 of Saccharomyces cerevisiae. To establish whether the S.
      mansoni cDNA clone could complement yeast ScIMP4-defective mutants, we
      constructed a yeast haploid strain that coded for a truncated Imp4p protein. This
      mutant strain was treated with different DNA damaging agents, but showed only MMS
      sensitivity. The functional homology between the ScIMP4 gene and the cDNA from S.
      mansoni was verified by partial complementation of the mutant yeast with the
      worm's gene. This gene appears to be involved in DNA repair and RNA metabolism in
      both S. mansoni and S. cerevisiae.

PMID- 17189634
TI  - Prostaglandin E2 mid-trimester evacuation of the uterus for women with a previous
      cesarean section.

PMID- 17189632
TI  - Molecular methods for diagnosis of Entamoeba histolytica in a clinical setting:
      an overview.
AB  - The range of clinical outcomes following Entamoeba histolytica infection is
      likely to be influenced by the different strains of the parasite already existing
      in our population. There is a need for developing faster, reliable and
      reproducible methods for identifying the different strains of E. histolytica.
      This would have a major impact on the subsequent course of treatment given to
      patients. In the post-genomic era, different loci of the Entamoeba genome have
      been targeted for developing suitable probes and genetic markers. This review
      highlights the development made in this direction and the possibility of using
      these methods for routine testing of this parasite in clinical samples.

PMID- 17189635
TI  - Selective thin-layer chromatography of 4-R-1,2,4-triazoles.
AB  - A convenient and selective TLC of 4-R-1,2,4-triazoles (Rtrz) and nitrogen
      containing aromatic rings is presented (molecules 1-11). This simple revelation
      method implies a complexation of heterocycles to Co(II) ions on a TLC plate,
      followed by a subsequent modification of the reduction potential which enables
      oxidation of Co(II) by permanganate.

PMID- 17189636
TI  - Multi-exon out of frame deletion of the FBN1 gene leading to a severe juvenile
      onset cardiovascular phenotype in Marfan syndrome.
AB  - Marfan syndrome is caused by mutations in fibrillin-1, a large gene spanning
      approximately 200 kb of genomic DNA on chromosome 15q21. So far, more than 600
      different mutations have been identified, accounting for 60-90% of all Marfan
      syndrome cases, the vast majority being single nucleotide exchanges as well as
      small deletions and insertions. Only four major rearrangements have been
      described in the literature so far. We have screened 11 individuals fulfilling
      the diagnostic criteria of Marfan syndrome but negative for point mutations in
      the fibrillin-1 gene by SSCP and/or direct sequencing, for large rearrangements.
      We report here the largest known de novo and out of frame deletion in the
      fibrillin-1 gene in a patient fulfilling the diagnostic criteria of Marfan
      syndrome. We identified the deletion breakpoints at the genomic and transcript
      levels and studied the expression of the mutated allele at the transcript and
      protein level. We conclude that large rearrangements may account for a non
      negligible proportion of all Marfan cases.

PMID- 17189637
TI  - Dimeric core structure of modular stator subunit E of archaeal H+ -ATPase.
AB  - Archaeal H(+)-ATPase (A-ATPase) is composed of an A(1) region that hydrolyzes ATP
      and an integral membrane part A(0) that conducts protons. Subunit E is a
      component of peripheral stator(s) that physically links A(1) and A(0) parts of
      the A-ATPase. Here we report the first crystal structure of subunit E of A-ATPase
      from Pyrococcus horikoshii OT3 at 1.85 A resolution. The protomer structure of
      subunit E represents a novel fold. The quaternary structure of subunit E is a
      homodimer, which may constitute the core part of the stator. To investigate the
      relationship with other stator subunit H, the complex of subunits EH was prepared
      and characterized using electrophoresis, mass spectrometry, N-terminal sequencing
      and circular dichroism spectroscopy, which revealed the polymeric and highly
      helical nature of the EH complex with equimolar stoichiometry of both the
      subunits. On the basis of the modular architecture of stator subunits, it is
      suggested that both cytoplasm and membrane sides of the EH complex may interact
      with other subunits to link A(1) and A(0) parts.

PMID- 17189638
TI  - Specific interactions of the wing domains of FOXA1 transcription factor with DNA.
AB  - FOX (forkhead box) transcription factors have diverse regulatory roles in
      development, signaling, and longevity, as well as being able to bind stably to
      target sites in silent chromatin. Crystal structure analysis showed that the FOXA
      DNA binding domain folds into a helix-turn-helix (HTH) motif flanked on either
      side by "wings" of polypeptide chain. The wings have the potential to interact
      with the DNA minor groove along the long axis of the DNA helix, flanking the HTH
      interactions with the major groove. Diverse FOX family homologs exist, and
      structural studies with certain DNA target sites suggest that neither of the wing
      regions are well ordered or provide a stable contribution to DNA target site
      binding. However, FOXA1 binds certain DNA target sites with high affinity, and as
      a monomer. To determine whether the wing domains contribute to stable DNA
      binding, we assessed complexes of FOXA with high and lower affinity DNA target
      sites by hydroxyl radical footprinting and site-directed mutagenesis. The data
      revealed clear protections predicted for wing interactions at the high affinity
      target, but less so at the lower affinity target, indicating that the wing
      domains stably interact with high affinity DNA sites for FOXA proteins.

PMID- 17189639
TI  - Production of authentic SARS-CoV M(pro) with enhanced activity: application as a
      novel tag-cleavage endopeptidase for protein overproduction.
AB  - The viral proteases have proven to be the most selective and useful for removing
      the fusion tags in fusion protein expression systems. As a key enzyme in the
      viral life-cycle, the main protease (M(pro)) is most attractive for drug design
      targeting the SARS coronavirus (SARS-CoV), the etiological agent responsible for
      the outbreak of severe acute respiratory syndrome (SARS) in 2003. In this study,
      SARS-CoV M(pro) was used to specifically remove the GST tag in a new fusion
      protein expression system. We report a new method to produce wild-type (WT) SARS
      CoV M(pro) with authentic N and C termini, and compare the activity of WT
      protease with those of three different types of SARS-CoV M(pro) with additional
      residues at the N or C terminus. Our results show that additional residues at the
      N terminus, but not at the C terminus, of M(pro) are detrimental to enzyme
      activity. To explain this, the crystal structures of WT SARS-CoV M(pro) and its
      complex with a Michael acceptor inhibitor were determined to 1.6 Angstroms and
      1.95 Angstroms resolution respectively. These crystal structures reveal that the
      first residue of this protease is important for sustaining the substrate-binding
      pocket and inhibitor binding. This study suggests that SARS-CoV M(pro) could
      serve as a new tag-cleavage endopeptidase for protein overproduction, and the WT
      SARS-CoV M(pro) is more appropriate for mechanistic characterization and
      inhibitor design.

PMID- 17189641
TI  - Consecutive binding of chlorophylls a and b during the assembly in vitro of light
      harvesting chlorophyll-a/b protein (LHCIIb).
AB  - The apoprotein of the major light-harvesting chlorophyll a/b complex (LHCIIb) is
      post-translationally imported into the chloroplast, where membrane insertion,
      protein folding, and pigment binding take place. The sequence and molecular
      mechanism of the latter steps is largely unknown. The complex spontaneously self
      organises in vitro to form structurally authentic LHCIIb upon reconstituting the
      unfolded recombinant protein with the pigments chlorophyll a, b, and carotenoids
      in detergent micelles. Former measurements of LHCIIb assembly had revealed two
      apparent kinetic phases, a faster one (tau1) in the range of 10 s to 1 min, and a
      slower one (tau2) in the range of several min. To unravel the sequence of events
      we analysed the binding of chlorophylls into the complex by using time-resolved
      fluorescence measurements of resonance energy transfer from chlorophylls to an
      acceptor dye attached to the apoprotein. Chlorophyll a, offered in the absence of
      chlorophyll b, bound with the faster kinetics (tau1) exclusively whereas
      chlorophyll b, in the absence of chlorophyll a, bound predominantly with the
      slower kinetics (tau2). In double-jump experiments, LHCIIb assembly could be
      dissected into a faster chlorophyll a and a subsequent, predominantly slower
      chlorophyll b-binding step. The assignment of the faster and the slower kinetic
      phase to predominantly chlorophyll a and exclusively chlorophyll b binding,
      respectively, was verified by analysing the assembly kinetics with a circular
      dichroism signal in the visible domain presumably reflecting the establishment of
      pigment-pigment interactions. We propose that slow chlorophyll binding is
      confined to the exclusively chlorophyll b binding sites whereas faster binding
      occurs to the chlorophyll a binding sites. The latter sites can bind both
      chlorophylls a and b but in a reversible fashion as long as the complex is not
      stabilised by proper occupation of the chlorophyll b sites. The resulting two
      step model of LHCIIb assembly is able to reconcile the highly specific binding
      sites containing either chlorophyll a or b, as seen in the recent crystal
      structures of LHCIIb, with the observation of promiscuous binding sites able to
      bind both chlorophyll a and b in numerous reconstitution analyses of LHCIIb
      assembly.

PMID- 17189640
TI  - UTP-bound and Apo structures of a minimal RNA uridylyltransferase.
AB  - 3'-Uridylylation of RNA is emerging as a phylogenetically widespread phenomenon
      involved in processing events as diverse as uridine insertion/deletion RNA
      editing in mitochondria of trypanosomes and small nuclear RNA (snRNA) maturation
      in humans. This reaction is catalyzed by terminal uridylyltransferases (TUTases),
      which are template-independent RNA nucleotidyltransferases that specifically
      recognize UTP and belong to a large enzyme superfamily typified by DNA polymerase
      beta. Multiple TUTases, recently identified in trypanosomes, as well as a U6
      snRNA-specific TUTase enzyme in humans, are highly divergent at the protein
      sequence level. However, they all possess conserved catalytic and UTP recognition
      domains, often accompanied by various auxiliary modules present at the termini or
      between conserved domains. Here we report identification, structural and
      biochemical analyses of a novel trypanosomal TUTase, TbTUT4, which represents a
      minimal catalytically active RNA uridylyltransferase. The TbTUT4 consists of only
      two domains that define the catalytic center at the bottom of the nucleoside
      triphosphate and RNA substrate binding cleft. The 2.0 Angstroms crystal structure
      reveals two significantly different conformations of this TUTase: one molecule is
      in a relatively open apo conformation, whereas the other displays a more compact
      TUTase-UTP complex. A single nucleoside triphosphate is bound in the active site
      by a complex network of interactions between amino acid residues, a magnesium ion
      and highly ordered water molecules with the UTP's base, ribose and phosphate
      moieties. The structure-guided mutagenesis and cross-linking studies define the
      amino acids essential for catalysis, uracil base recognition, ribose binding and
      phosphate coordination by uridylyltransferases. In addition, the cluster of
      positively charged residues involved in RNA binding is identified. We also report
      a 2.4 Angstroms crystal structure of TbTUT4 with the bound 2'
      deoxyribonucleoside, which provides the structural basis of the enzyme's
      preference toward ribonucleotides.

PMID- 17189643
TI  - Malignant progression in pleomorphic xanthoastrocytoma: personal experience and
      review of the literature.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare primary low-grade astrocytic tumor,
      recently classified as a neuroglial tumor. It generally occurs in children and
      young adults and shows benign behaviour (WHO II), although an anaplastic variant
      and malignant potential have been described. Pleomorphic xanthoastrocytomas with
      malignant transformation have been reported in three out of eight patients
      operated on for this type of tumor in our department in the last 15 years. The
      three patients were two adult women and a child, the primary tumors were located
      in the cortex of the right temporal lobe, and treatment consisted of complete
      surgical resection. Histological examination revealed simple PXA in two patients
      and a PXA with anaplastic foci in the other. Mean recurrence time was 5.7 years,
      with the original xanthoastrocytoma evolving to glioblastoma in two cases and
      anaplastic astrocytoma in the third. All three patients underwent a second
      operation, followed by adjuvant therapies. Two died from tumor progression and
      one from brain edema after intracerebral haemorrhage. A review of the available
      PXA literature dating back to 1979 revealed 16 cases of primary anaplastic
      astrocytoma and 21 cases of PXA with malignant transformation. Our experience
      adds three more cases of malignant transformations, outlining once again the
      potential malignancy of pleomorphic xanthoastrocytomas and the fact that
      prognosis in these cases is the same as for primary anaplastic astrocytoma and
      glioblastoma. Analysis of glioneuronal markers, Ki67 and p53 in all pleomorphic
      xanthoastrocytomas did not prove to be a discriminating factor to identify a
      subgroup of xanthoastrocytomas prone to malignancy. Accordingly, these tumors
      demand close long-term clinical and radiological follow-up.

PMID- 17189644
TI  - Prediction of the subcellular location of apoptosis proteins.
AB  - Apoptosis proteins have a central role in the development and the homeostasis of
      an organism. These proteins are very important for understanding the mechanism of
      programmed cell death. The function of an apoptosis protein is closely related to
      its subcellular location. Based on the concept that the subcellular location of
      an apoptosis protein is mainly determined by its amino acid sequence, a new
      algorithm for prediction of the subcellular location of an apoptosis protein is
      proposed. By using of a distinctive set of information parameters derived from
      the primary sequence of 317 apoptosis proteins, the increment of diversity (ID),
      the sole prediction parameter, is calculated. The higher predictive success rates
      than the previous other algorithms is obtained by the jackknife tests using the
      expanded dataset. Our prediction results show that the local compositions of twin
      amino acids and hydropathy distribution are very useful to predict subcellular
      location of protein.

PMID- 17189642
TI  - Disease progression in vascular cognitive impairment: cognitive, functional and
      behavioural outcomes in the Consortium to Investigate Vascular Impairment of
      Cognition (CIVIC) cohort study.
AB  - BACKGROUND AND PURPOSE: Empirical studies to clarify the outcomes in Vascular
      Cognitive Impairment (VCI) are needed. We compared cognitive, functional, and
      behavioural outcomes in patients with VCI to patients with no cognitive
      impairment (NCI), and Alzheimer's disease (AD). METHODS: Secondary analysis of
      the Consortium to Investigate Vascular Impairment of Cognition (CIVIC), a multi
      centre Canadian memory clinic 30-month cohort study. RESULTS: Of 1347 patients,
      938 were eligible for follow-up, of whom 239 (24.5%) were lost and 29 (3%) had
      died. Of the remaining 697 patients, 125 had NCI, 229 had VCI, and 343 had AD at
      baseline. Compared to people with NCI, of whom 20-40% showed progression based on
      cognitive and functional measures, those with VCI were more likely to progress
      (50-65%), as were people with AD (50-80%) (p<0.01). More people with VCI showed
      progression of affective symptoms (30%) than those with NCI (12%) or AD (15%
      p<0.01). Progression of impaired judgment (rated clinically) in VCI (15%) was
      similar to AD (11%) but more common than in NCI (4%, p<0.01). CONCLUSIONS: Most
      people with VCI show readily detectable progression by 30 months. Depressive
      symptoms were more common and more progressive in VCI than in Alzheimer's
      disease, whereas clinical evidence of progressive executive dysfunction was
      common in both AD and VCI.

PMID- 17189645
TI  - Prostate cancer chemoprevention: current status and future prospects.
AB  - Chemoprevention is a strategy that aims to reduce the incidence and burden of
      cancer through the development of agents to prevent, reverse or delay the
      carcinogenic process. Prostate cancer is a suitable target for prevention because
      it has a high incidence and prevalence, as well as a long latency and disease
      related mortality, and furthermore it is a disease in which lifestyle and
      environmental factors may play critical roles. The development of chemoprevention
      strategies against prostate cancer will have a huge impact, both medically and
      economically. Large-scale clinical trials suggest that some agents such as
      selenium, lycopene, soy, green tea, vitamins D and E, anti-inflammatory and
      inhibitors of 5alpha-reductase are effective in preventing prostate cancer.
      Although each agent has the potential to affect the natural history of the
      disease, it is important to develop strategies to strategically proceed for the
      design and selection of test agents in order to demonstrate clinical benefit with
      the minimum of adverse effects. Appropriate selection of agent(s), disease stage,
      trial design and endpoints is critical in selecting the most promising regimens
      to accomplish these goals. This review highlights the present status of prostate
      cancer chemoprevention and discusses future prospects for chemopreventive
      strategies that are safe and clinically beneficial.

PMID- 17189646
TI  - Identification of pectenotoxins in plankton, filter feeders, and isolated cells
      of a Dinophysis acuminata with an atypical toxin profile, from Chile.
AB  - A bloom of Dinophysis acuminata produced, in autumn of 2005, a closure of the
      scallop harvesting in Bahia Inglesa, in the Chilean III region. Isolated cells of
      this Dinophysis species were shown to contain 180 pg cell(-1) of pectenotoxin 2
      but neither okadaic acid nor any of its analogs or derivatives (at least at a
      detectable level). Examination of plankton and filter-feeder samples covering an
      area of ca. 350 km, from the location where the toxicity was recorded to Bahia
      Tongoy, showed that the unique toxin profile found in the first bloom was
      widespread over that part of Chile and persisted for months. The analysis were
      carried out by HPLC-ESI-MS using positive ionization mode, with a detection limit
      below 2 ng of OA mL(-1) of methanolic extract. This is the first report of the
      presence of pectenotoxins in the plankton of the Pacific coast of America and in
      the studied filter feeders. This is also the first report of a Dinophysis species
      containing pectenotoxins and not any toxin of the okadaic acid group.

PMID- 17189647
TI  - Remote facilitation in the Fourier domain.
AB  - To explore spatial interactions between visual mechanisms in the Fourier domain
      we measured detection thresholds for vertical and horizontal sine-wave gratings
      (4.4 deg diameter) over a range of spatial frequencies (0.5-23 c/deg) in the
      presence of grating and plaid masks with component contrasts of 8%, orientations
      of +/-45 degrees and a spatial frequency of 1c/deg. The mask suppressed the
      target grating over a range of +/-1 octave, and the plaid produced more
      suppression than the grating, consistent with summation of mask components in a
      broadly tuned contrast gain pool. At greater differences in spatial frequency (
      approximately 3 octaves), the plaid and grating masks both produced about 3 dB of
      facilitation (they reduced detection thresholds by a factor of about square root
      2). At yet further distances ( approximately 4 octaves) the masks had no effect.
      The facilitation cannot be attributed to a reduction of uncertainty by the mask
      because (a) it occurs for mask components that have very different spatial
      frequencies and orientations from the test and (b) the large stimulus size and
      central fixation point mean there was no spatial uncertainty that could be
      reduced. We suggest the results are due to long-range sensory interactions (in
      the Fourier domain) between mask and test-channels. The effects could be due to
      either direct facilitation or disinhibition.

PMID- 17189648
TI  - The accumulation levels of PAHs, PCBs and DDTs are related in an inverse way to
      the size of a benthic amphipod (Echinogammarus stammeri Karaman) in the River Po.
AB  - The accumulation of polychlorinated biphenyls (PCBs), polycyclic aromatic
      hydrocarbons (PAHs) and DDTs were investigated in gammarids captured at three
      sites along the middle River Po; the first was located upstream and the other two
      were at increasing distances downstream of the confluence of a polluted
      tributary, the River Lambro. Using a GC-MS technique, the levels of PCBs, PAHs
      and DDTs were determined separately in large and small gammarids as well as in
      the fine fraction of sediment samples collected along the sites of capture.
      Results confirm the River Lambro as a source of these chemicals to the River Po,
      and show that bioaccumulation differences exist between small and large
      individuals, the former being more contaminated particularly by PCBs and DDTs.
      This is likely the result of several interacting factors such as contaminant
      bioavailability, gammarid-size effects on kinetic parameters and feeding
      selectivity. The bioaccumulation patterns of PCBs and DDTs, and their higher
      biota-sediment accumulation factors (BSAF), are consistent with chemical
      properties and suggest a dietary disequilibrium found only 10 km downstream from
      the tributary, and in smaller amphipods. Present results show that gammarids may
      represent an additional source of contaminants, particularly of chlorinated
      compounds, to the many organisms feeding on them, with a higher risk for those
      which prey selectively on smaller gammarids.

PMID- 17189649
TI  - Pelvic cytoreduction with rectosigmoid resection.

PMID- 17189650
TI  - Nonylphenol stimulates fecundity but not population growth rate (lambda) of
      Folsomia candida.
AB  - The toxicity of nonylphenol (NP) to springtails was pronounced at 40 mg/kg dry
      weight soil, at which no animals survived. Body length and fecundity were the
      individual life-history traits significantly stimulated by sublethal
      concentrations of NP during a 64-day experiment. However, the effects of NP on
      these traits did not result in a statistically significant increase in population
      growth rate (lambda). Decomposition analysis indicated that fecundity was the
      main contributor to the (non-significant) changes observed in lambda. However,
      since the elasticity of fecundity was very low, large changes in fecundity
      resulted in a minimal effect on lambda. Juvenile survival had the highest
      elasticity of all traits, but was not affected by NP, and therefore did not
      contribute to effects on lambda. This study confirms previous studies showing
      that effects of chemicals on individual life-history traits are attenuated at the
      population level and that lambda is an appropriate endpoint for ecotoxicological
      studies.

PMID- 17189651
TI  - Cross validation with the mood disorder questionnaire (MDQ) of an instrument for
      the detection of hypomania in Spanish: the 32 item hypomania symptom check list
      (HCL-32).
AB  - BACKGROUND: The detection and diagnosis of present or past hypomanic episodes is
      of key importance for the differential diagnosis between depressive disorders and
      type II bipolar disorder. However, there are few instruments available to
      satisfactorily screen for the latter condition. The Hypomania Symptom Checklist
      32 (HCL-32) is a self-applied questionnaire with 32 hypomania items and 8
      severity and functional impact items which is being developed in several European
      countries for this purpose. Our aim was to develop and validate the psychometric
      properties of the HCL-32 scale in Spain in patients with bipolar disorder and to
      compare its properties with other instruments available for the detection of
      bipolar II disorder. METHODS: Patients were selected from 15 psychiatric
      outpatient departments, diagnosed with type I or type II bipolar disorder (BDI
      and BDII) and unipolar major depression (MD) according to DSM-IV-TR criteria. A
      control group of healthy subjects (HS) was likewise assessed. The patient
      selection criteria included a well-established diagnosis and a stable disorder
      and pharmacological treatment. The HCL-32 was administered to 237 subjects
      distributed among the above groups, on two occasions four weeks apart. We
      analysed the internal consistency, test-retest reliability and discriminative
      capacity of the HCL-32. RESULTS: The internal consistency of the Spanish version
      of the HCL-32, evaluated by Cronbach's alpha, was 0.94. Mean of affirmative
      questions by group were 21.2 (SD 5.8) for BDI, 19.3 (SD 6.2) for BDII, 8.6 (SD
      6.6) for MD and 6.6 (SD 6.1) for HS, with statistically significant differences
      between them (Kruskal-Wallis test, p<0.001). Concurrent validity using the
      diagnosis variable was 0.72. Test-retest reliability was 0.90. We analysed the
      best cut-off point by means of a ROC curve analysis; for 14 affirmative
      responses, a sensitivity of 0.85 95%CI (0.78, 0.91) and specificity of 0.79,
      95%CI (0.72, 0.87) were obtained. The positive and negative probability ratios
      were 4.1 and 5.3 (1/0.19 respectively). HCL-32 shows a dual factor structure of
      items, one as an energy-activity factor and another one as a factor involving
      items related to disinhibition and problems with self-control and attention.
      LIMITATIONS: The sample size of bipolar patients (particularly type BDII) should
      be increased in further studies. CONCLUSIONS: The Spanish version of the HCL-32
      has good psychometric properties and sufficient sensitivity and specificity,
      detecting 8 out of every 10 patients with BD. The HCL-32 is a useful screening
      tool of patients with bipolar disorder in clinical settings. In its present form
      it adequately discriminates between bipolar and unipolar or healthy subjects, but
      not between BD I and BII.

PMID- 17189652
TI  - Negative association between a history of obstetric complications and the number
      of neurological soft signs in first-episode schizophrenic disorder.
AB  - We examined the relationship between a history of obstetric complications (OCs)
      and the number of neurological soft signs (NSS) in a group of 132 patients
      experiencing their first episode of psychosis. We measured NSS by means of a
      comprehensive standardized assessment and gained information on a selection of
      nine OCs from the patient's mother. Contrary to our expectations we found
      significantly more NSS in the group of patients without a history of OCs. This
      effect was independent of medication in the group of patients with a
      schizophrenic disorder, but not in the entire group. It is possible that the
      patients with a history of OCs carry fewer genes for schizophrenia (and NSS) and
      'needed' the OCs to develop schizophrenia.

PMID- 17189653
TI  - Selective serotonin reuptake inhibitor (fluoxetine) decreases the effects of
      ghrelin on memory retention and food intake.
AB  - Ghrelin (Ghr) is an appetite stimulating hormone that is produced peripherally,
      by the stomach, and centrally as well. Previous investigations show that Ghr
      increases food intake and memory retention in rats, and that extra-hypothalamic
      structures, such as the hippocampus, participate in these effects. In the present
      work we analyzed the effect on food intake and memory retention induced by Ghr
      after serotonin (5-HT) availability modification at the serotoninergic synapses.
      Animals only treated with a selective serotonin reuptake inhibitor (SSRI),
      fluoxetine (FLU) 5 mg/kg or clomipramine (CLO) 2.5 and 5 mg/kg, showed a
      significant reduction in both food intake and memory retention. On the contrary,
      Ghr administration induces a significant increase in food intake and a dose
      dependent increase in short and long term memory retention. When the animals were
      treated with FLU prior to Ghr injection, the food intake induced, as well as the
      expression of short and long term memory retention, was decreased. In conclusion,
      evidence presented in this paper suggests that the effects of Ghr on both feeding
      and memory retention in extra-hypothalamic structures such as the hippocampus,
      could depend on the availability of 5-HT.

PMID- 17189654
TI  - Home telemonitoring of vital signs and cardiorespiratory signals in heart failure
      patients: system architecture and feasibility of the HHH model.
AB  - BACKGROUND: The Home or Hospital in Heart Failure Study (HHH) is a European
      Community funded trial (QLGA-CT-2001-02424) which compares usual care of heart
      failure (HF) with three home-based interventions in a multicenter, multicountry
      (Italy, Poland and UK), randomized controlled clinical trial. Home telemonitoring
      (HT) of clinical parameters represents a potential alternative (or addition) to
      traditional home care models. Nocturnal respiratory disorders (periodic
      breathing, sleep apnea) are very common in HF, and are associated with increased
      morbidity and mortality. We developed an integrated HT system for monitoring of
      both vital signs and respiration. All measurements were patient-managed. This
      paper describes the architecture of this system, and assesses its feasibility.
      METHODS AND RESULTS: 461 clinically stable patients were randomized first to
      usual vs home-monitored care; the latter were further randomized to 3 strategies.
      Over a 12-month follow-up 2 of these 3 groups (195 patients, age: 60+/-11 years,
      NYHA class II-III: 97%, LVEF 28+/-7%) underwent self-administered home monitoring
      of vital signs (weekly--12 parameters using an interactive voice response system)
      and respiration (monthly--24-hour recording). Data were transmitted over
      conventional telephone lines; 81% of actually practicable vital signs
      measurements were completed by the patients (range: 75% (PL)-93% (UK)), as well
      as 92% of practicable respiratory recordings (range: 85% (PL)-99% (UK)). 87% of
      nighttime recordings were eligible for the study (good quality signals for > or =
      2.5 h). CONCLUSIONS: This study, the largest so far, demonstrates that self
      managed home telemonitoring of both vital signs and respiration is feasible in HF
      patients, with surprisingly high compliance. We found an excellent rate of
      acceptable nocturnal respiratory recordings, which are those with the greatest
      clinical relevance.

PMID- 17189655
TI  - Fluorescent measurement of microalgal neutral lipids.
AB  - Nile Red, a dye that fluoresces at defined wavelengths depending upon the
      polarity of the surrounding medium, has been proposed to determine the neutral
      lipid content of microalgal cells. Herein we communicate modifications to this
      technique that facilitate its use as a high-throughput screening technology, as
      well as improving its accuracy and versatility.

PMID- 17189656
TI  - Transient neurological adverse effects following low dose radiation therapy for
      early stage testicular seminoma.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to estimate the rate of
      neurological adverse effects following radiotherapy for testicular seminoma and
      to disclose possible dose-related effects. PATIENTS AND METHODS: All seminoma
      patients (n=346) treated 1980-2001 at our department with radiotherapy as the
      only treatment modality following orchiectomy constitute the study group (median
      follow-up 10 years). Since 1980, clinical data including possible side effects
      have systematically been recorded in these patients. These records were used to
      identify men with possible neurological adverse effects. Univariate logistic
      regression was used to estimate dose-related effects. RESULTS: Overall, 11 men
      (3.2%) with neurological symptoms probably related to radiotherapy were
      identified. Seven men treated with 25.2-36 Gray presented with sensory symptoms
      about 2 months following radiotherapy. These symptoms resolved in all but one
      after 1-3 months. The remaining four men (dose 36-40 Gray) had motor impairment
      which lasted at least one year, but none had persistent pareses at long-term
      follow-up. There was a statistically significant (p=0.02) increase in rate of
      motor symptoms with higher dose. CONCLUSIONS: Although motor impairment is
      unlikely to occur at current standard doses for seminomas, physicians should be
      ware of the sensory symptoms these men may exhibit.

PMID- 17189657
TI  - Enterococcus and Lactobacillus contamination of raw milk in a farm dairy
      environment.
AB  - Enterococci and lactobacilli are ubiquitously found in the intestinal microflora
      of humans and animals. The aim of the present study was to determine the
      importance of bovine faeces as a source of these organisms in raw milk. One
      hundred and fifty six putative enterococci and 362 lactobacilli were isolated
      from bovine faeces (n=26), cows' teats, raw milk, the milking machine and the
      milking environment on one farm. The clonal relationships of each group were
      investigated using Pulsed-Field Gel Electrophoresis and representatives of the
      different clusters were identified by repetitive DNA element (rep)-PCR
      fingerprinting, protein profiling, phenylalanyl-tRNA synthase (pheS) sequence
      analysis or 16S rDNA gene sequencing. Lactobacilli were present at approximately
      3 orders of magnitude greater than enterococci in the bovine faeces. The majority
      of the bovine faecal enterococcal isolates were identified as Aerococcus
      viridans. Seven teat isolates belonged to a potential novel Aerococcus sp. and
      one bovine faecal isolate to a potential second novel Aerococcus sp. The
      lactobacilli present in the bovine faeces were predominantly Lactobacillus
      mucosae and Lactobacillus brevis, with small numbers of Lactobacillus plantarum.
      Only one Enterococcus (a strain of E. casseliflavus) out of 76 and one
      Lactobacillus (a strain of L. parabuchneri/kefir) out of 247 of the bovine faecal
      isolates was found in the milk. The major source of these bacteria in the milk
      was the milking equipment.

PMID- 17189658
TI  - Strategies for the investigation and control of process-related impurities in
      drug substances.
AB  - The understanding, identification, quantification and control of impurities in
      drug substances are essential as new molecular entities are evaluated in clinical
      development. As chemical processes used to produce drug substances mature from
      the early phases of development through registration, a concomitant maturing of
      process-related impurity understanding and control is required. This paper
      outlines strategies available to pharmaceutical scientists to aid in that
      understanding. Methodology aspects for impurity investigations are discussed
      along with an emphasis on understanding the origin and fate of impurities to
      guide decisions on process controls and specifications. Orthogonal analytical
      approaches for impurity investigations to provide a complete understanding of a
      drug substance impurity profile and to aid chemical process development are
      described. Special considerations necessary for stereochemical impurity
      investigations are also discussed. Considerations for control of toxic impurities
      include sensitive and selective analytical methodology and determination of the
      process capability for removing the impurity. A case study is given where routine
      analytical testing for a toxic impurity was not required because a high impurity
      rejection efficiency of the synthetic process was demonstrated. Quality
      assessment of starting materials from multiple sources and the impact of starting
      material impurities on the impurity profile of the drug substance are discussed
      with illustrative examples. Knowledge gained from these investigations provides a
      sound basis for setting specifications for impurities in key starting materials.

PMID- 17189659
TI  - The role of actin, actomyosin and microtubules in defining cell shape during the
      differentiation of Naegleria amebae into flagellates.
AB  - Differentiation of Naegleria amebae into flagellates was used to examine the
      interaction between actin, actomyosin and microtubules in defining cell shape.
      Amebae, which lack microtubules except during mitosis, differentiate into
      flagellates with a fixed shape and a complex microtubule cytoskeleton in 120 min.
      Based on earlier models of ameboid motility it has been suggested that actomyosin
      is quiescent in flagellates. This hypothesis was tested by following changes in
      the cytoskeleton using three-dimensional reconstructions prepared by confocal
      microscopy of individual cells stained with antibodies against actin and tubulin
      as well as with phalloidin and DNase I. F-actin as defined by phalloidin staining
      was concentrated in expanding pseudopods. Most phalloidin staining was lost as
      cells rounded up before the onset of flagellum formation. Actin staining with a
      Naegleria-specific antibody that recognizes both F- and G-actin was confined to
      the cell cortex of both amebae and flagellates. DNase I demonstrated G-actin
      throughout all stages. Most of the actin in the cortex was not bound by
      phalloidin yet was resistant to detergent extraction suggesting that it was
      polymerized. The microtubule cytoskeleton of flagellates was intimately
      associated with this actin cortex. Treatment of flagellates with cytochalasin D
      produced a rapid loss of flagellate shape and the appearance of phalloidin
      staining while latrunculin A stabilized the flagellate shape. These results
      suggest that tension produced by an actomyosin network is required to maintain
      the flagellate shape. The rapid loss of the flagellate shape induced by drugs,
      which specifically block myosin light chain kinase, supports this hypothesis.

PMID- 17189660
TI  - Comparing contributions of soil versus root colonization to variations in
      stomatal behavior and soil drying in mycorrhizal Sorghum bicolor and Cucurbita
      pepo.
AB  - In prior studies we learned that colonization of soil can be as important as
      colonization of roots in determining mycorrhizal influence on the water relations
      of host plants. Here we use a path analysis modeling approach to test (a) whether
      quantity of hyphae in soil contributes to variations in stomatal behavior and
      soil drying, and (b) whether soil colonization or root colonization has a
      stronger influence on these stomatal and soil drying responses. Experiments were
      performed on Sorghum bicolor and Cucurbita pepo, with soils and roots colonized
      by a mixture of Glomus intraradices and Gigaspora margarita. Soil colonization
      generally made more significant contributions to stomatal conductance than did
      root colonization. Soil colonization did not make significant direct
      contributions to soil water potential measures (soil water potential at stomatal
      closure or soil drying rate), whereas root colonization did contribute a
      potentially important path to each. The findings further support a role for
      mycorrhization of the soil itself in contributing to the regulation of stomatal
      behavior of host plants.

PMID- 17189661
TI  - Caffeine as a flavor additive in soft-drinks.
AB  - Over 60% of soft-drinks sold in the United States contain caffeine, a mildly
      addictive psycho-active chemical, as a flavor additive. Using sweeteners as
      controls, we assessed whether caffeine has flavor activity in a cola soft-drink.
      A forced-choice triangle discrimination methodology was used to determine
      detection thresholds of caffeine in sweeteners and a cola beverage. The subjects
      (n=30, 28 female, 23+/-4 years old) were trained tasters and completed over 1600
      discrimination tests during the study. The mean detection thresholds for caffeine
      in the sweet solutions were: 0.333+/-0.1mM sucrose; 0.467+/-0.29 mM aspartame;
      0.462+/-0.3mM sucralose, well below the concentration in common cola beverages
      (0.55-0.67 mM). A fixed concentration of caffeine, corresponding to the
      concentration of caffeine in a common cola beverage (0.67 mM) was added to the
      sweeteners and a non-caffeinated cola beverage. Subjects could distinguish
      between caffeinated and non-caffeinated sweeteners (p<0.001), but all subjects
      failed to distinguish between caffeinated and non-caffeinated cola beverage
      (p=1.0). Caffeine has no flavor activity in soft-drinks yet will induce a
      physiologic and psychologic desire to consume the drink.

PMID- 17189662
TI  - Neighbourhood fast food environment and area deprivation-substitution or
      concentration?
AB  - It has been hypothesised that deprived neighbourhoods have poorer quality food
      environments which may promote the development of obesity. We investigated
      associations between area deprivation and the location of the four largest fast
      food chains in Scotland and England. We found statistically significant increases
      in density of outlets from more affluent to more deprived areas for each
      individual fast-food chain and all chains combined. These results provide support
      for a 'concentration' effect whereby plausible health-damaging environmental risk
      factors for obesity appear to be 'concentrated' in more deprived areas of England
      and Scotland.

PMID- 17189663
TI  - Synthesis and cytotoxicity of some new eriocalyxin B derivatives.
AB  - Eriocalyxin B (1) was regarded as the promising candidate for new anticancer
      agent because of its potent activity and novel mechanism of action. Systematic
      modifications of 1 were done, and nineteen derivatives were synthesized and their
      cytotoxicities against five tumor cell lines were evaluated. The structure
      activity relationship (SAR) of 1 confirmed that the alpha,beta-unsaturated ketone
      moieties in ring A and D are the leading active sites; the 7,20-epoxy moiety, OH
      6 and OH-7 play an important role in keeping the cytotoxicity. The 6,7-seco
      derivative 19 had remarkable activity while derivative 20 oxidized from 19 was
      completely inactive, which suggested that the carboxyl group could destroy the
      cytoxicity of 20 despite the presence of alpha,beta-unsaturated ketone moiety.

PMID- 17189664
TI  - Synthesis, characterization and antimicrobial activity of Fe(II), Zn(II), Cd(II)
      and Hg(II) complexes with 2,6-bis(benzimidazol-2-yl) pyridine ligand.
AB  - 2,6-Bis(benzimidazol-2-yl)pyridine (L) ligand and complexes [M(L)Cl(2)] and
      [Fe(L)(2)](ClO(4))(2) (M=Zn, Cd, Hg) have been synthesized. The geometries of the
      [M(L)Cl(2)] complexes were derived from theoretical calculation in DGauss/DFT
      level (DZVP basis set) on CACHE. The central M(II) ion is penta-coordinated and
      surrounded by N(3)Cl(2) environment, adopting a distorted trigonal bipyramidal
      geometry. The ligand is tridentate, via three nitrogen atoms to metal centre and
      two chloride ions lie on each side of the distorted benzimidazole ring. In the
      [Fe(L)(2)](ClO(4))(2) complex, the central Fe(II) ion is surrounded by two (3N)
      units, adopting a octahedral geometry. The elemental analysis, molecular
      conductivity, FT-Raman, FT-IR (mid-, far-IR), (1)H, and (13)C NMR were reported.
      The antimicrobial activities of the free ligand, its hydrochloride salt, and the
      complexes were evaluated using the disk diffusion method in dimethyl sulfoxide
      (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method,
      against 10 bacteria and the results compared with that for gentamycin. Antifungal
      activities were reported for Candida albicans, Kluyveromyces fragilis,
      Rhodotorula rubra, Debaryomyces hansenii, Hanseniaspora guilliermondii, and the
      results were referenced against nystatin, ketaconazole, and clotrimazole
      antifungal agents. In most cases, the compounds tested showed broad-spectrum
      (Gram positive and Gram negative bacteria) activities that were either more
      effective than or as potent as the references. The binding of two most
      biologically effective compounds of zinc and mercury to calf thymus DNA has also
      been investigated by absorption spectra.

PMID- 17189665
TI  - Synthesis of some new bioactive 3-amino-2-mercapto-5,6,7,8
      tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one derivatives.
AB  - Nine new 2-(substituted phenyl)/alkyl[1,3,4]thiadiazolo[2,3-b]-6,7,8,9
      tetrahydrobenzo(b)thieno[3,2-e]pyrimidin-5(4H)-ones, six new 3-amino-2-[(2-oxo-2
      (aryl)ethyl)thio]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-ones,
      one 2-mercapto[1,3,4]thiadiazolo[2,3-b]-6,7,8,9-tetrahydrobenzo(b)thieno[3,2
      e]pyrimidin-5(4H)-one and one 2-chloromethyl[1,3,4]thiadiazolo[2,3-b]-6,7,8,9
      tetrahydrobenzo(b)thieno[3,2-e]pyrimidin-5(4H)-one were synthesized from 3-amino
      2-mercapto-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one. The newly
      synthesized compounds were characterized by analytical and spectral data.
      Compounds were screened for anti-inflammatory, CNS depressant and antimicrobial
      activities. Some of the compounds exhibited promising biological activities.

PMID- 17189666
TI  - Outcome for children infected with congenital toxoplasmosis in the first
      trimester and with normal ultrasound findings: a study of 36 cases.
AB  - OBJECTIVE: We wished to investigate the prognosis of children infected with
      Toxoplasma gondii during the first trimester of pregnancy and whose ultrasound
      findings were entirely normal, in order to find out whether congenital
      toxoplasmosis did or did not justify termination of pregnancy if there was no
      fetal abnormality on ultrasound. STUDY DESIGN: A prospective and retrospective
      study was carried out by 12 French centers who enrolled 36 children infected with
      T. gondii during the first trimester of pregnancy and whose ultrasound
      examinations showed no anomaly. The outcome of these children after the age of 12
      months (mean 50 months, range 12-144 months) was analyzed. RESULTS: Of the 36
      infected children, 28 (78%) presented subclinical toxoplasmosis. Only specific
      IgG antibodies persisted after 1 year. The principal manifestation in 7 children
      (19%) was chorioretinitis without major vision loss. Their intellectual
      development was entirely normal. One child (3%) developed severe congenital
      toxoplasmosis. CONCLUSION: Since 97% of children infected with toxoplasmosis
      during the first trimester of pregnancy are asymptomatic or only slightly
      affected, we believe that in such circumstances termination of pregnancy is not
      indicated. However, appropriate treatment is essential and prenatal ultrasound
      examinations should be free of any anomaly.

PMID- 17189667
TI  - Effect of plant harvest on methane emission from two constructed wetlands
      designed for the treatment of wastewater.
AB  - The emission of methane from two constructed wetlands [a free water surface flow
      system (FWS) and a subsurface flow system (SF)], constructed for the treatment of
      waste water, was evaluated at different sites inhabited by reeds (Phragmites
      communis), to test the effects of plant harvest. High methane emission was
      recorded immediately after harvesting in both wetlands. Several days after
      harvesting, the emission decreased in the FWS but remained high in the SF. The
      variation was significantly influenced by temperature, with lower emission and
      higher dissolved CH(4) in water occurring at lower temperatures. Both the
      emission and concentration of dissolved CH(4) were also influenced significantly
      by water quality, wetland design, level of stalk butt left above the water level,
      etc. The methane flux was explained on the basis of rizhospheric methanogenic and
      methanotrophic microbial populations. FISH analysis indicated the presence of
      Type A and Type B methanotrophs in both wetlands, and the methane flux was
      directly influenced by the quantitative variation in methanogenic and
      methanotrophic bacteria in both wetlands.

PMID- 17189668
TI  - Antimycin A induces apoptosis in As4.1 juxtaglomerular cells.
AB  - Antimycin A, an inhibitor of electron transport in mitochondria, has been used as
      reactive oxygen species (ROS) generator in the biological system. Here, we
      investigated the in vitro effect of antimycin A on apoptosis in As4.1
      juxtaglomerular cells. Antimycin A efficiently induced apoptosis in As4.1 cells
      as evidenced by flow cytometric detection of sub-G(1) DNA content, annexin V
      binding assay and DAPI staining. This apoptotic process was accompanied by loss
      of mitochondrial transmembrane potential (DeltaPsi(m)), Bcl-2 decrease, caspase-3
      activation and PARP cleavage. All of caspase inhibitors tested in this experiment
      failed to rescue As4.1 cells from antimycin A-induced cell death at the time of
      48 h in view of sub-G(1) cells and annexin V positive staining cells. However,
      with regard to the mitochondrial membrane potential (DeltaPsi(m)), pan caspase
      inhibitor (Z-VAD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) at the concentration
      of 25 microM noticeably decreased the loss of mitochondrial membrane potential
      (DeltaPsi(m)) in antimycin A-treated cells. Taken together, we have demonstrated
      that antimycin A as an inhibitor of electron transport in mitochondria potently
      induces apoptosis in As4.1 juxtaglomerular cells.

PMID- 17189669
TI  - Trichostatin A and 5-aza-2'-deoxycytidine switch S1P from an inhibitor to a
      stimulator of motility through epigenetic regulation of S1P receptors.
AB  - The histone deacetylase inhibitor, trichostatin A (TSA), and the DNA
      methyltransferase inhibitor, 5-aza-2'-deoxycytidine (Aza-dC), induced epigenetic
      regulation of sphingosine-1-phosphate (S1P) receptors in human melanoma cells,
      switching S1P from motility inhibitor to stimulator. Quantitative PCR revealed
      increased expression of S1P(1) and S1P(3), associated with S1P-induced
      chemotaxis, and decreased expression of S1P(2), associated with motility
      inhibition. Expression of lysophosphatidic acid (LPA) receptors was less
      affected. The TSA effect was reversible suggesting no mutational change, and Aza
      dC treatment resulted in demethylation of a putative S1P(1) promoter. S1P
      receptors, therefore, appear to be susceptible to epigenetic regulation,
      accompanied by altered cellular functionality.

PMID- 17189670
TI  - Anti-EGFR and ErbB-2 antibodies attenuate cyclooxygenase-2 expression and
      cooperatively inhibit survival of human colon cancer cells.
AB  - Cyclooxygenase-2 (COX-2) is a transcriptional target and downstream effector of
      the ErbB-1 (EGFR) and ErbB-2 signaling pathways. We found that anti-EGFR and anti
      ErbB-2 antibodies inhibited ERK phosphorylation and downregulated COX-2 protein
      expression in HCA-7 human colon carcinoma cells. Both antibodies also augmented
      the cytotoxic effects of the selective COX-2 inhibitor, NS-398. Inhibition of
      EGFR and ErbB-2 attenuated cell growth by increasing cell death, and the antibody
      combination suppressed cell growth to a greater extent than did either antibody
      alone. In conclusion, EGFR and ErbB-2 regulate ERK-mediated COX-2 expression and
      their selective inhibition enhanced NS-398-induced cell death. Cooperative
      inhibition of cell growth by EGFR and ErbB-2 blockade suggests the therapeutic
      potential of targeting multiple ErbB receptors.

PMID- 17189671
TI  - Cigarette smoke as a trigger for the dioxin receptor-mediated signaling pathway.
AB  - Dioxins and dioxin-like chemicals cause a wide range of pathologies including
      carcinogenesis, immune dysfunction, and developmental/reproductive abnormalities.
      Most of these toxic effects are mediated by aryl hydrocarbon receptor (AhR; also
      called the dioxin receptor), a ligand-activated transcription factor.
      Constitutive activation of AhR via genetic manipulation causes development of
      cancers, inflammation and immune abnormality in mice even without exposure to
      xenobiotic ligands. Recent investigation disclosed that cigarette smoke contains
      high levels of agonists for AhR and strongly activates the dioxin signaling
      pathway. In this review, we describe and discuss possible roles of AhR activation
      in cigarette smoke-related pathologies, especially focusing on carcinogenesis,
      inflammation, atherosclerosis, immune dysfunction and teratogenesis.

PMID- 17189672
TI  - Pharmacological and histopathological characterization of a hyperalgesia model
      induced by freeze lesion.
AB  - Induction of a freeze lesion in human skin is an experimental model of
      hyperalgesia that allows assessing the antihyperalgesic effects of traditional
      non-steroidal anti-inflammatory drugs (NSAIDs). We have investigated whether this
      model is also sensitive to selective cyclooxygenase (COX)-2 inhibitors and have
      characterized morphological substrates of the generated hyperalgesia in the skin.
      In eight healthy subjects, a freeze lesion was induced and mechanical pain
      thresholds (MPT) were tested for 5h following administration of the non-selective
      COX inhibitor diclofenac (75mg), the COX-2-selective inhibitor parecoxib (40mg)
      or placebo in a randomized, double-blind cross-over study. In five additional
      healthy subjects, biopsies were taken from normal skin and the area of freezing
      injury. Induction of the freeze lesion resulted in hyperalgesia expressed by a
      decrease of MPT after 24h. Diclofenac and parecoxib, but not placebo,
      statistically significantly elevated MPT. Histochemical and Western blot analyses
      of skin biopsies revealed a strong upregulation of COX-2, a slight decrease of
      COX-1 and activation of nuclear factor kappa B (NF-kappaB) in the area of the
      freezing injury. These findings indicate that the freeze lesion model is
      sensitive to NSAIDs including selective COX-2 inhibitors, and that NF-kappaB
      dependent COX-2 upregulation contributes to the hyperalgesia in this model.

PMID- 17189674
TI  - Classifying microRNAs in cancer: the good, the bad and the ugly.
AB  - MicroRNAs (miRNAs) have quite recently emerged as a novel class of gene
      regulators. Many miRNAs exhibit altered expression levels in cancer, and we are
      only starting to understand the functional consequences of the loss or gain of
      particular miRNAs to the cancerous phenotype. miRNAs can be classified with
      regard to their role in cancer as the Good, the Bad and the Ugly. The "Good",
      those miRNAs that are innocent bystanders in the oncogenic transformation
      process, whose expression profile might even be used for cancer diagnosis or
      prognosis. The "Bad", those miRNAs that are causally linked to tumorigenesis and
      directly modify tumor suppressor- or oncogenic- pathways. And the "Ugly", those
      miRNAs whose inappropriate loss or gain destabilizes the cellular identity of a
      tumor, which indirectly results in enhanced phenotypic variability and
      progression of the tumor. Hereunder we will discuss the possible ways in which
      miRNAs can be relevant to cancer biology, and possible experimental strategies
      for elucidating the mechanisms involved.

PMID- 17189673
TI  - Lycopene as a natural protector against gamma-radiation induced DNA damage, lipid
      peroxidation and antioxidant status in primary culture of isolated rat
      hepatocytes in vitro.
AB  - The present study was designed to evaluate the radioprotective effect of
      lycopene, a naturally occurring dietary carotenoid, on gamma-radiation induced
      toxicity in cultured rat hepatocytes. The cellular changes were estimated using
      lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS),
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced
      glutathione (GSH), ceruloplasmin, vitamins A, E, C and uric acid. The DNA damage
      was analysed by single cell gel electrophoresis (comet assay). The increase in
      the severity of DNA damage was observed with the increase in gamma-radiation dose
      (1, 2 and 4 Gy) in cultured rat hepatocytes. TBARS were increased significantly
      whereas the levels of GSH, vitamins C, E and A, ceruloplasmin, uric acid and
      antioxidant enzymes were significantly decreased in gamma-irradiated groups. The
      maximum damage to hepatocytes was observed at 4 Gy irradiation. Pretreatment with
      lycopene (1.86, 9.31 and 18.62 microM) showed a significant decrease in the
      levels of TBARS and DNA damage. The antioxidant enzymes increased significantly
      along with the levels of GSH, vitamins A, E, C, uric acid and ceruloplasmin. The
      maximum protection of hepatocytes was observed at 9.31 muM of lycopene
      pretreatment. Thus, our results show that pretreatment with lycopene offers
      protection against gamma-radiation induced cellular damage and can be developed
      as an effective radioprotector during radiotherapy.

PMID- 17189675
TI  - Immunohistological findings of suppurative granulomas of Yersinia enterocolitica
      appendicitis: a report of two cases.
AB  - We report on the histopathologic and immunohistologic findings of two cases of
      suppurative granulomatous appendicitis of Yersinia enterocolitica (Y. ent.).
      Using formalin-fixed, paraffin-embedded materials, polymerase chain reaction
      revealed Y. ent. in both cases. Histologically, the epithelioid cell granulomas
      (EPGs) were transmural in both cases. The EPGs were predominantly nonsuppurative,
      and were surrounded by a lymphoid cuff composed of small lymphocytes. A portion
      of EPGs contained suppuration of the centers of the granulomas (central
      microabscesses). The EPGs were composed of numerous histiocytes with or without
      epithelioid cell features, along with scattered small T-lymphocytes and
      plasmacytoid monocytes. None of the EPGs contained monocytoid B-cells.
      Immunohistochemical study demonstrated that EPGs were usually surrounded by
      surface IgM/D+ small mantle zone lymphocytes. Moreover, CNA.42 immunostaining
      occasionally demonstrated residual follicular dendritic cells in the center of
      the EPGs. The overall histomorphologic and immunohistochemical findings
      demonstrated that the EPGs with Y. ent. are of the B-cell negative
      hypersensitivity type and occur in reactive germinal centers. In one case,
      regional lymph nodes contained EPGs showing the same histologic and
      immunohistologic findings as those of the appendix. The present study indicates
      that among abscesses forming epithelioid granulomatous lesions, EPGs with Y. ent.
      were B-cell negative granulomas, and it demonstrates histopathologic and
      immunohistochemical findings different from those of cat scratch disease and
      lymphogranuloma venerum, which contain numerous monocytoid B-cells.

PMID- 17189678
TI  - Mechanisms of immunotherapy in allergic rhinitis.
AB  - Allergic rhinitis is a common condition, but many people still experience
      suboptimal control of symptoms despite measures such as allergen avoidance, intra
      nasal steroids and antihistamines. Specific immunotherapy (SIT) has been used for
      many years, but though many studies show clinical efficacy, its mechanism of
      action is still not clearly understood. Earlier studies showed changes in
      antibodies and it may be that SIT works through mechanisms that alter the ratio
      of 'protective' IgG4 to 'pro-allergenic' IgE. Other studies have shown a
      reduction in eosinophil migration to nasal mucosa as well as a reduction in
      inflammatory mediator release including basophil histamine release. More recent
      studies have proposed that SIT works through inhibition of T-helper 2 lymphocytes
      (Th2) which preferentially produce cytokines that promote allergic responses. SIT
      may cause a deviation from Th2 to Th1 (T-helper 1 lymphocytes) or may induce T
      regulatory cells (T-regs) which inhibit Th2 responses directly or through
      inhibitory cytokines.

PMID- 17189676
TI  - Bacopa monniera prevents from aluminium neurotoxicity in the cerebral cortex of
      rat brain.
AB  - Bacopa monniera is a perennial herb, and is used as a nerve tonic in ayurveda, a
      traditional medicinal system in India. Aluminium-induced neurotoxicity is well
      known and different salts of aluminium have been reported to accelerate oxidative
      damage to biomolecules like lipids, proteins and nucleic acids. The objective of
      the present study was to investigate whether Bacopa monniera could potentially
      inhibit aluminium toxicity in the cerebral cortex. Male Wister rats (8 months
      old) were administered with AlCl(3) orally at a dose of 50mg/kg/day in drinking
      water for 1 month. Experimental rats were given AlCl(3) along with Bacopa
      monniera extract at a dose of 40 mg/kg/day. One group of rats was treated with l
      deprenyl at a dose of 1mg/kg/day along with AlCl(3) treatment. We have observed
      that Bacopa monniera prevented accumulation of lipid and protein damage
      significantly, which resulted from aluminium intake. Decline in the activity of
      endogenous antioxidant enzymes associated with aluminium administration was also
      inhibited by Bacopa monniera extract. The potential of Bacopa monniera to inhibit
      Al-induced oxidative stress was observed to be similar to that of l-deprenyl,
      which was taken as standard. The potential of Bacopa monniera extract to prevent
      aluminium neurotoxicity was reflected at the microscopic level as well,
      indicative of its neuroprotective effects. These findings strongly implicate that
      Bacopa monniera has potential to protect brain from oxidative damage resulting
      from aluminium toxicity.

PMID- 17189677
TI  - Reliable serodiagnosis of imported cystic echinococcosis with a commercial
      indirect hemagglutination assay.
AB  - A commercially available indirect hemagglutination assay (IHA) (Echinococcosis
      Fumouze; Laboratoires Fumouze, Levallois-Perret, France) was evaluated using sera
      from 52 patients with proven cystic echinococcosis. The specificity was assessed
      using 247 sera from patients with various parasitic, bacterial, viral, and fungal
      infectious diseases; sera containing autoimmune antibodies; and sera from healthy
      blood donors. With a cutoff value for a positive result of 320 (as recommended by
      the manufacturer), the sensitivity and specificity were 88% and 98.4%; with a
      cutoff of 160, the sensitivity and specificity were 94% and 95.1%, respectively.
      The IHA is rapid, easy to perform, and is a very sensitive serodiagnostic test
      for cystic echinococcosis.

PMID- 17189679
TI  - NF-kB activation and p38 phosphorilation in microglial cells infected with
      Leptospira or exposed to partially purified leptospiral lipoproteins.
AB  - Recently, we have shown a differential susceptibility of non-pathogenic vs.
      pathogenic leptospires to phagocytosis and killing by microglial cells. Although
      all ingested to some extent, only the pathogenic strains survived intracellularly
      while the non-pathogenic ones were killed in a time-dependent manner. By the same
      infection model, here we demonstrate that microglial cells respond to Leptospira
      infection with a time- and dose-dependent induction of molecular signals (p38
      phosphorilation and NF-kB activation) and the production of soluble factors
      (cytokines and nitric oxide). Such bio-molecular response is predominantly
      observed against the pathogenic Leptospira; the phenomenon is reproduced by
      leptospiral lipoproteins and, to a lower extent, by leptospiral-derived LPS.
      These data provide initial evidence that Leptospira affects microglial cell
      response in a different manner depending upon the virulence of the infecting
      strain; specific bacterial components happen to be involved in the induction of
      such pathogen-induced immune response.

PMID- 17189681
TI  - Analysis of 275 patients with sarcoidosis over a 38 year period; a single
      institution experience.
AB  - BACKGROUND: Sarcoidosis is a systemic granulomatous disease with unknown
      etiology. OBJECTIVES: We evaluated seasonal variation, demographic, clinical and
      diagnostic features of sarcoidosis in recently diagnosed symptomatic patients in
      the whole cohort (275 patients) and in the subgroups according to the estimated
      disease course (subacute course group vs. chronic course group). We also
      developed a prediction model to predict the course of sarcoidosis using simple
      clinical and demographic variables. MATERIAL AND METHODS: Two hundred and seventy
      five patients with sarcoidosis. MEASUREMENTS AND STATISTICS: Roger's test, chi
      square, t-test and multiple logistic regression were used. RESULTS: The
      distribution of cumulative monthly diagnosis was the lowest in November (fall)
      (p<0.01). Seasonal pattern was influenced by age and gender. Constitutional
      symptoms, stages 2 and 3 diseases and the absence of erythema nodosum were highly
      significant parameters for chronic course. Using these variables, the developed
      model had a specificity of 93.1% and its positive predictive value was 89.5%.
      Progression of the disease was documented 6.4% in subacute group vs. 32.1% in
      chronic group (p=0.00001). Preventive effect of smoking was more pronounced in
      females than in males in our cohort. CONCLUSIONS: Further well-designed and large
      prospective studies are required to better understand the importance of these
      findings, and to validate the prediction model presented here.

PMID- 17189682
TI  - Long-term non-invasive ventilation increases chemosensitivity and leptin in
      obesity-hypoventilation syndrome.
AB  - BACKGROUND: Long-term nocturnal non-invasive mechanical ventilation (NIMV) is an
      effective treatment for obesity-hypoventilation syndrome (OHS), improving central
      carbon dioxide (CO(2)) sensitivity. Leptin might contribute to sustain adequate
      ventilation in obesity. The aim of the study was to investigate the role of
      leptin in the OHS pathogenesis looking at its relationship to CO(2) sensitivity
      before and after NIMV in OHS patients. METHODS: In six obese patients (3F/3M;
      aged 63+/-9 yr; BMI 47.0+/-4.5 kg/m(2)) with OHS and without obstructive sleep
      apnoea-hypopnoea (OSAH) diurnal arterial blood gases, fasting plasma leptin
      concentration and CO(2) chemosensitivity were determined before and after 10.3+/
      5.6 (range 6-20) months of NIMV. RESULTS: After NIMV improvements were observed
      in gas exchange (PaO(2) from 51.3+/-6.7 to 75.0+/-10.3 mmHg, p<0.01; PaCO(2) from
      55.5+/-4.8 to 43.7+/-1.2 mmHg, p<0.01; [HCO(3)(-)] from 33.3+/-3.8 to 29.8+/-1.7
      mmol/l, p<0.05) and CO(2) chemosensitivity, measured as P(0.1)/PetCO(2) slope
      (from 0.09+/-0.07 to 0.18+/-0.07 cmH(2)O/mmHg, p<0.05) and V(E)/PetCO(2) slope
      (from 0.4+/-0.3 to 0.9+/-0.5l/min/mmHg, p=0.07). Plasma leptin increased from
      34.5+/-21.1 ng/ml to 50.2+/-22.9 ng/ml (p<0.01) after NIMV and changes of the
      P(0.1)/PetCO(2) slope correlated with percent changes of plasma leptin
      (r(2)=0.79, p<0.05). CONCLUSIONS: These findings suggest a possible role of
      leptin in the recovery of neuromuscular response to hypercapnia obtained during
      long-term nocturnal NIMV in OHS patients without OSAH.

PMID- 17189683
TI  - Information available at cut rates: structure and mechanism of ribonucleases.
AB  - Ribonucleases are counterweights in the balance of gene expression and are also
      involved in the maturation of functional RNA. Recent structural data reveal how
      ribonucleases recognize and cleave targets, in most cases with the catalytic
      assistance of metal cofactors. Many of these enzymes are 'processive', in that
      they make multiple scissions following the binding of substrates;
      crystallographic data can account for this solution behaviour. These data not
      only explain how ribonucleases turn over transcripts, but also provide hints
      about how they often play dual roles in quality control checks on structured RNA.

PMID- 17189680
TI  - Cytokine regulation of MMP-9 in peripheral glia: implications for pathological
      processes and pain in injured nerve.
AB  - Matrix metalloproteinase-9 (MMP-9) is an extracellular protease that is induced
      in Schwann cells hours after peripheral nerve injury and controls axonal
      degeneration and macrophage recruitment to the lesion. Here, we report a robust
      (90-fold) increase in MMP-9 mRNA within 24 h after rat sciatic nerve crush (1 to
      60 days time-course). Using direct injection into a normal sciatic nerve, we
      identify the proinflammatory cytokines TNF-alpha and IL-1beta as potent
      regulators of MMP-9 expression (Taqman qPCR, zymography). Myelinating Schwann
      cells produced MMP-9 in response to cytokine injection and crush nerve injury.
      MMP-9 gene deletion reduced unstimulated neuropathic nociceptive behavior after
      one week post-crush and preserved myelin thickness by protecting myelin basic
      protein (MBP) from degradation, tested by Western blot and immunofluorescence.
      These data suggest that MMP-9 expression in peripheral nerve is controlled by key
      proinflammatory cytokine pathways, and that its removal protects nerve fibers
      from demyelination and reduces neuropathic pain after injury.

PMID- 17189684
TI  - Simple criterion for selection of flavonoid compounds with anti-HIV activity.
AB  - Flavonoid compounds represent an important natural source of antiretrovirals for
      AIDS therapy due to their significant anti-HIV-1 activity and low toxicity. Here
      we propose a simple theoretical criterion to discriminate active from inactive
      flavonoids that is suitable for rapid in silico screening of flavonoid libraries,
      and selection and optimization of lead compounds with anti-HIV-1 activity.

PMID- 17189685
TI  - Synthesis and HIV-1 integrase inhibitory activity of spiroundecane(ene)
      derivatives.
AB  - Fifteen 2,4-dioxaspiro[5.5]undecane ketone and 2,4-dioxa-spiro[5.5]undec-8-ene
      (spiroundecane(ene)) derivatives were synthesized using the Diels-Alder reaction.
      Inhibition of human immunodeficiency virus integrase (IN) was examined. Eight
      spiroundecane(ene) derivatives inhibited both 3'-processing and strand transfer
      reactions catalyzed by IN. SAR studies showed that the undecane core with at
      least one furan moiety is preferred for IN inhibition. Moreover, crosslinking
      experiments showed that spiroundecane derivatives did not affect IN-DNA binding
      at concentrations that block IN catalytic activity, indicating spiroundecane
      derivatives inhibit preformed IN-DNA complex. The moderate toxicity of
      spiroundecane(ene) derivatives encourages the further design of therapeutically
      relevant analogues based on this novel chemotype of IN inhibitors.

PMID- 17189687
TI  - Hydrolytic cleavage of DNA by quercetin zinc(II) complex.
AB  - Quercetin zinc(II) complex was investigated focusing on its hydrolytic activity
      toward DNA. The complex successfully promotes the cleavage of plasmid DNA,
      producing single and double DNA strand breaks. The amount of conversion of
      supercoiled form (SC) of plasmid to the nicked circular form (NC) depends on the
      concentration of the complex as well as the duration of incubation of the complex
      with DNA. The rate of conversion of SC to NC is 1.68x10(-4) s(-1) at pH 7.2 in
      the presence of 100 microM of the complex. The hydrolytic cleavage of DNA by the
      complex is supported by the evidence from free radical quenching, thiobarbituric
      acid-reactive substances (TBARS) assay, and T4 ligase ligation.

PMID- 17189686
TI  - Weak base dispiro-1,2,4-trioxolanes: potent antimalarial ozonides.
AB  - Thirty weak base 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized.
      Amino amide trioxolanes had the best combination of antimalarial and
      biopharmaceutical properties. Guanidine, aminoxy, and amino acid trioxolanes had
      poor antimalarial activity. Lipophilic trioxolanes were less stable metabolically
      than their more polar counterparts.

PMID- 17189688
TI  - 3-Mercaptopropionic acids as efficacious inhibitors of activated thrombin
      activatable fibrinolysis inhibitor (TAFIa).
AB  - A novel series of cyclic potent, selective, small molecule, thiol-based
      inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) and
      the crystal structures of TAFIa inhibitors bound to porcine pancreatic
      carboxypeptidase B are described. Three series of cyclic arginine and lysine
      mimetic inhibitors vary significantly in their selectivity against other human
      basic carboxypeptidases, carboxypeptidase N and carboxypeptidase B. (-)2a
      displays TAFIa IC50 = 3 nM and 600-fold selectivity against CPN. Inhibition of
      TAFIa with (rac)2a resulted in dose dependent acceleration of human plasma clot
      lysis in vitro and was efficacious as an adjunct to tPA in an in vivo rabbit
      jugular vein thrombolysis model.

PMID- 17189689
TI  - Synthesis and evaluation of novel chromogenic aminopeptidase substrates for
      microorganism detection and identification.
AB  - The amides 8a-e and 10a-c were prepared as chromogenic aminopeptidase substrates.
      A range of microorganisms were grown in the presence of these compounds and
      coloured colonies were produced in several cases after addition of acetic acid
      thus giving potential methods for the detection of aminopeptidase activity and
      for microorganism identification.

PMID- 17189690
TI  - 3-Substituted-(5-arylfuran-2-ylcarbonyl)guanidines as NHE-1 inhibitors.
AB  - The C-3 substituents effect on NHE-1 inhibitory activity of (5-arylfuran-2
      ylcarbonyl)guanidines, previously identified as potent NHE-1 inhibitors, was
      investigated. The introduction of amine or alkyl groups at the 3-position of the
      furan ring, next to the acylguanidine moiety, remarkably improves NHE-1
      inhibitory potency. Especially the important finding is that 5-(2,5
      dichloro)phenyl and 5-(2-methoxy-5-chloro)phenyl derivatives exhibit high NHE-1
      inhibitory activities (IC50 < 0.02 microM) that match those of 3-unsubstituted
      derivatives.

PMID- 17189691
TI  - Rational design, synthesis, and structure-activity relationship of
      benzoxazolones: new potent mglu5 receptor antagonists based on the fenobam
      structure.
AB  - A novel class of potent and stable mGlu5 receptor antagonists was developed by
      combining information from a high-throughput screening campaign with the
      structure of the known anxiolytic fenobam. Representative compounds from this
      class show favorable pharmacokinetic properties and are active in an in vivo
      model of anxiety.

PMID- 17189692
TI  - Development of new pyrrolopyrimidine-based inhibitors of Janus kinase 3 (JAK3).
AB  - A new class of bicyclic pyrrolopyrimidine-based Janus kinase 3 (JAK-3) inhibitors
      are described. Many of these inhibitors showed low nanomolar activity against JAK
      3.

PMID- 17189693
TI  - Design of cell-permeable, fluorescent activity-based probes for the lysosomal
      cysteine protease asparaginyl endopeptidase (AEP)/legumain.
AB  - Asparaginyl endopeptidase (AEP), also known as legumain, is a cysteine protease
      that has been ascribed roles in antigen presentation yet its exact role in human
      biology remains poorly understood. We report here, the use of a positional
      scanning combinatorial library of peptide AOMKs containing a P1 aspartic acid to
      probe the P2, P3, and P4 subsite specificity of endogenous legumain. Using
      inhibitor specificity profiles of cathepsin B and legumain, we designed
      fluorescent ABPs that are highly selective, cell-permeable reagents for
      monitoring legumain activity in complex proteomes.

PMID- 17189694
TI  - Synthesis and biological evaluation of thiazolidine-2-one 1,1-dioxide as
      inhibitors of Escherichia coli beta-ketoacyl-ACP-synthase III (FabH).
AB  - A series of cyclic sulfones has been synthesized and their activity against beta
      ketoacyl-ACP-synthase III (FabH) has been investigated. The compounds are
      selectively active against Escherichia coli FabH (ecFabH), but not Mycobacterium
      tuberculosis FabH (mtFabH) or Plasmodium falciparum KASIII (PfKASIII). The
      activity against ecFabH ranges from 0.9 to >100microM and follows a consistent
      general SAR trend. Many of the compounds were shown to have antimalarial activity
      against chloroquine (CQ)-sensitive (D6) P. falciparum (IC(50)=5.3microM for the
      most potent inhibitor) and some were active against E. coli (MIC=6.6microg/ml for
      the most potent inhibitor).

PMID- 17189695
TI  - Synthesis and antibacterial evaluation of a novel series of rifabutin-like
      spirorifamycins.
AB  - A novel series of spirorifamycins was synthesized and their antibacterial
      activity evaluated both in vitro and in vivo. This new series of rifamycins shows
      excellent activity against Staphylococcus aureus that is equivalent to rifabutin.
      However, some compounds of the series exhibit lower MICs than rifabutin against
      rifampin-resistant strains of S. aureus. Further, compound 2e exhibits comparable
      efficacy in vivo in a murine model of S. aureus septicemia model following
      administration by either oral or parenteral dosing routes.

PMID- 17189696
TI  - Should women at high risk of breast cancer have screening magnetic resonance
      imaging (MRI)?

PMID- 17189697
TI  - LET-99, GOA-1/GPA-16, and GPR-1/2 are required for aster-positioned cytokinesis.
AB  - At anaphase, the mitotic spindle positions the cytokinesis furrow [1]. Two
      populations of spindle microtubules are implicated in cytokinesis: radial
      microtubule arrays called asters and bundled nonkinetochore microtubules called
      the spindle midzone [2-4]. In C. elegans embryos, these two populations of
      microtubules provide two consecutive signals that position the cytokinesis
      furrow: The first signal is positioned midway between the microtubule asters; the
      second signal is positioned over the spindle midzone [5]. Evidence for two
      cytokinesis signals came from the identification of molecules that block midzone
      positioned cytokinesis [5-7]. However, no molecules that are only required for,
      and thus define, the molecular pathway of aster-positioned cytokinesis have been
      identified. With RNAi screening, we identify LET-99 and the heterotrimeric G
      proteins GOA-1/GPA-16 and their regulator GPR-1/2 [10-12] in aster-positioned
      cytokinesis. By using mechanical spindle displacement, we show that the anaphase
      spindle positions cortical LET-99, at the site of the presumptive cytokinesis
      furrow. LET-99 enrichment at the furrow depends on the G proteins. GPR-1 is
      locally reduced at the site of cytokinesis-furrow formation by LET-99, which
      prevents accumulation of GPR-1 at this site. We conclude that LET-99 and the G
      proteins define a molecular pathway required for aster-positioned cytokinesis.

PMID- 17189698
TI  - Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole
      (YC-1) as novel anti-leukemia agents.
AB  - As part of our continuing search for potential anticancer drug candidates in YC-1
      analogs, several 1-benzyl-3-(substituted aryl)-5-methylfuro[3,2-c]pyrazoles were
      synthesized and evaluated for their cytotoxicity against HL-60 cell line. Among
      these compounds, 1-benzyl-3-(5-hydroxymethyl-2-furyl)-5-methylfuro[3,2-c]pyrazole
      (1) showed more potency than YC-1. Through investigation of action mechanism, it
      was found that compound 1 induced terminal differentiation of HL-60 cells toward
      granulocyte lineage and promoted HL-60 cell differentiation by regulation of Bcl
      2 and c-Myc proteins. Meanwhile, compound 1 also demonstrated apoptosis inducing
      effect. Such anti-leukemia mechanism of action is apparently different from that
      of YC-1 which mainly works by inducing apoptosis, but not cell differentiation.
      Therefore, compound 1 is identified here as a new lead compound of cell
      differentiating agent and apoptosis inducer for further development of new anti
      leukemia agents.

PMID- 17189699
TI  - Synthesis of fluorescent molecular probes specific for the receptor of
      blepharismone, a mating-inducing pheromone of the ciliate Blepharisma japonicum.
AB  - Blepharismone (gamone 2) is a mating-inducing pheromone of the ciliate
      Blepharisma japonicum. N-Pyrenylbutyryl-blepharismone and N-biphenylacetyl
      blepharismone, which are fluorescent derivatives of blepharismone, were
      synthesized as molecular probes for the gamone 2 receptor. Further, we proved
      that they have inhibitory activities against the blepharismone-induced monotypic
      pairing of B. japonicum.

PMID- 17189702
TI  - Characterization of novel DNA-binding proteins expressed in snake oocyte cDNA
      library.
AB  - DNA-binding proteins play pivotal roles in transcription, DNA-replication,
      recombination/repair and determine cell-fate in all physiological conditions of
      differentiation, development and disease. As they are present in extremely small
      amounts in cells, their isolation/identification, particularly from scarce
      tissues is impracticable. We cloned the cDNA pool of snake (Ptyas mucosus)
      oocytes (a scarce tissue) in bacteria, overexpressed total library, purified and
      identified DNA-binding proteins expressed in the library. Although snake
      databases do not exist, we identified 23 DNA-binding proteins, obtained 10-15
      amino acids internal sequence tags of six of them and succeeded in PCR
      amplification of the cDNAs of five proteins. We employed electro spray ionization
      mass spectrometry, matrix assisted laser desorption/ionization time of flight and
      analyzed the results by peptide mass fingerprint (PMF) and various sequence BLAST
      analyses. Proteins identified were largely unanimous between the PMF and BLAST
      analyses. We expect these proteins to play important roles in snake embryonic
      development and differentiation. We arrived at homologous mouse proteins to some
      of the identified snake proteins and are working towards characterizing their
      structure and physiological function. Similar approaches shall prove valuable in
      isolation and identification of important factors from scarce carcinoma tissues,
      mammalian oocytes and early embryos, which might be involved in important
      functions like nuclear reprogramming, embryonic development and differentiation.

PMID- 17189701
TI  - Laminins containing the beta2 chain modulate the precise organization of CNS
      synapses.
AB  - Synapses are formed and stabilized by concerted interactions of pre-, intra-, and
      post-synaptic components; however, the precise nature of the intrasynaptic
      components in the CNS remains obscure. Potential intrasynaptic components include
      extracellular matrix molecules such as laminins; here, we isolate beta2
      containing laminins, including perhaps laminins 13 (alpha3beta2gamma3) and 14
      (alpha4beta2gamma3), from CNS synaptosomes suggesting a role for these molecules
      in synaptic organization. Indeed, hippocampal synapses that form in vivo in the
      absence of these laminins are malformed at the ultrastructural level and this
      malformation is replicated in synapses formed in vitro, where laminins are
      provided largely by the post-synaptic neuron. This recapitulation of the in vivo
      function of laminins in vitro suggests that the malformations are a direct
      consequence of the removal of laminins from the synapse. Together, these results
      support a role for neuronal laminins in the structural integrity of central
      synapses.

PMID- 17189700
TI  - Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction
      in a mouse model of SCA7 retinopathy.
AB  - We have approached the role of cellular stress in neurodegenerative diseases
      caused by polyglutamine expansion (polyQ) in the context of Spinocerebellar
      ataxia type 7 (SCA7) that includes retinal degeneration. Using the R7E mouse, in
      which polyQ-ataxin-7 is specifically over-expressed in rod photoreceptors, we
      previously showed that rod dysfunction correlated to moderate and prolonged
      activation of the JNK/c-Jun stress pathway. SCA7 retinopathy was also associated
      with reduced expression of rod-specific genes, including the transcription factor
      Nrl, which is essential for rod differentiation and function. Here, we report
      that R7E retinopathy is improved upon breeding with the JunAA knock-in mice, in
      which JNK-mediated activation of c-Jun is compromised. Expression of Nrl and its
      downstream targets, which are involved in phototranduction, are partially
      restored in the JunAA-R7E mice. We further show that c-Jun can directly repress
      the transcription of Nrl. Our studies suggest that polyQ-induced cellular stress
      leads to repression of genes necessary for neuronal fate and function.

PMID- 17189704
TI  - Suppression of the back proton-transfer from Asp85 to the retinal Schiff base in
      bacteriorhodopsin: a theoretical analysis of structural elements.
AB  - The transfer of a proton from the retinal Schiff base to the nearby Asp85 protein
      group is an essential step in the directional proton-pumping by
      bacteriorhodopsin. To avoid the wasteful back reprotonation of the Schiff base
      from Asp85, the protein must ensure that, following Schiff base deprotonation,
      the energy barrier for back proton-transfer from Asp85 to the Schiff base is
      larger than that for proton-transfer from the Schiff base to Asp85. Here, three
      structural elements that may contribute to suppressing the back proton-transfer
      from Asp85 to the Schiff base are investigated: (i) retinal twisting; (ii)
      hydrogen-bonding distances in the active site; and (iii) the number and location
      of internal water molecules. The impact of the pattern of bond twisting on the
      retinal deprotonation energy is dissected by performing an extensive set of
      quantum-mechanical calculations. Structural rearrangements in the active site,
      such as changes of the Thr89:Asp85 distance and relocation of water molecules
      hydrogen-bonding to the Asp85 acceptor group, may participate in the mechanism
      which ensures that following the transfer of the Schiff base proton to Asp85 the
      protein proceeds with the subsequent photocycle steps, and not with back proton
      transfer from Asp85 to the Schiff base.

PMID- 17189703
TI  - Expression and purification of a two-component flaviviral proteinase resistant to
      autocleavage at the NS2B-NS3 junction region.
AB  - Regulated proteolysis of the polyprotein precursor of West Nile virus (WNV) by
      the essential NS2B-NS3(pro)tease, a promising drug target for WNV inhibitors, is
      required for the propagation of infectious virions. Structural and drug design
      studies, however, require pilot-scale quantities of a pure and catalytically
      active WNV protease that is resistant to self-proteolysis. Autolytic cleavage at
      the NS2B-NS3 boundary leads to individual, non-covalently associated, NS2B and
      NS3 domains, together with residual amounts of the intact NS2B-NS3, in the NS2B
      NS3pro samples. We modified the cleavage site sequence of the NS2B-NS3 junction
      region and then developed expression and purification procedures to prepare a
      covalently linked, single-chain, NS2B-NS3pro K48A mutant construct. This
      construct exhibits high stability and functional activity and is thus well suited
      for the follow-up purification and structural and drug design studies.

PMID- 17189705
TI  - State, trait and biochemical influences on human anterior cingulate function.
AB  - The dorsal part of the human anterior cingulate cortex (dACC) is reliably
      activated in situations requiring cognitive control, especially during states of
      conflict. However, little is known about how individual differences in the neural
      characteristics of the dACC and major dimensions of behavior, affect this brain
      response. We recruited 28 healthy adults and employed a multi-modal neuroimaging
      approach combined with a task designed to specifically activate the human dACC
      and statistical path analysis to demonstrate clear roles for intelligence,
      personality and concentrations of neuronal N-acetylaspartate in determining dACC
      activation. These influences were comparable in magnitude to those associated
      with the experience of conflict. Our findings extend current understandings of
      the neural substrates of cognitive control by modeling the effect of neuronal
      viability, intelligence, and personality, on dACC activation. They also highlight
      the importance of considering enduring personal characteristics when mapping
      human brain-behavior relationships.

PMID- 17189707
TI  - The problem of cough and development of novel antitussives.
AB  - Cough is a very common clinical symptom and current therapies are largely
      ineffective, indicating a major unmet medial need. There is a pressing need to
      develop novel and safe antitussive therapies. This is likely to arise from better
      understanding of the sensory nerves involved in cough and the signalling pathways
      that are activated. A major therapeutic target should be sensitization of the
      cough reflex which is a feature of patients with both acute (virally induced)
      cough and chronic cough, including chronic idiopathic cough. Studies on human
      cough mechanisms are limited. There are several novel therapeutic approaches that
      are currently being explored. Perhaps the most promising drugs are transient
      receptor potential vanilloid-1 (TRPV(1)) antagonists, selective cannabinoid
      agonists (CB2 agonists), maxi-K channel openers and P2X3 antagonists. New cough
      therapies may target airway nerve sensitization and may best be delivered as
      inhalers to minimize any systemic effects. Understanding the intercellular
      signalling pathways involved in nociception may lead to novel drugs, such as p38
      mitogen-activated protein (MAP) kinase inhibitors, being used in the treatment of
      cough in the future. It is also likely that several novel treatments that are
      developed as analgesics will also prove to be beneficial in the treatment of
      cough.

PMID- 17189708
TI  - Tumour necrosis factor (TNF)alpha as a regulator of fat tissue mass in the
      Mediterranean gilthead sea bream (Sparus aurata L.).
AB  - The study was undertaken to analyze the lipolytic effect and transcriptional
      regulation of tumour necrosis factor (TNF)alpha in gilthead sea bream (Sparus
      aurata L.). The study was also focused on the transcriptional regulation and
      analysis of the 5-flanking region of lipoprotein lipase (LPL) in an attempt to
      identify cis-regulatory elements that would support the TNFalpha-mediated
      effects. The lipolytic effect of TNFalpha was evidenced by the increased release
      of glycerol in the culture medium of freshly isolated adipocytes. This
      observation, in addition to the summer up-regulation of TNFalpha transcripts in
      liver and mesenteric adipose tissue, supported a key role of TNFalpha as a fish
      limiting factor of tissue fat mass. Accordingly, TNFalpha expression in liver and
      mesenteric adipose tissue was reduced by fasting. Furthermore, the up-regulated
      expression of TNFalpha in the skeletal muscle of older fish can represent an
      adaptive response to limit the enhanced lipid influx towards muscle. A close
      positive association between LPL and TNFalpha transcripts supported the
      contribution of TNFalpha as a part of a regulatory network that exerts an
      inhibitory tonus upon the expression of LPL, which in turns limits the tissue
      uptake of fatty acids and the ultimate increase of tissue lipid reservoirs. The
      precise mechanism for the inhibition of LPL gene expression by TNFalpha remains
      to be established in fish, but analysis of the 5'-flanking region evidenced the
      conservation through vertebrate evolution of a functional OCT-1/NF-Y site that
      would mediate the TNFalpha effects on LPL expression.

PMID- 17189706
TI  - The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T
      cell receptor-signaling pathway.
AB  - Members of the c-Jun NH(2)-terminal kinase (JNK) family play crucial roles in
      cell activation, differentiation, and apoptosis. Although many studies have
      indicated that JNK1 and JNK2 have functional differences and redundancy, the
      upstream signaling pathway that selectively activates JNK1 or JNK2 remains
      unknown. In this study, we have revealed a selective mechanism of JNK activation,
      in which JNK2, but not JNK1, was regulated by CARMA1, a scaffold molecule, after
      stimulation of the T cell receptor (TCR). This CARMA1-dependent regulation of
      JNK2 worked through the scaffold molecule Bcl10, which was inducibly associated
      with JNK2 and served as a JNK-interacting protein (JIP)-like scaffold to assemble
      the kinases JNK2, MKK7, and TAK1. Finally, we showed that CARMA1- and Bcl10
      mediated JNK2 activation had a critical role in regulating the amount of c-Jun
      protein. Together, our studies provide genetic evidence that JNK1 and JNK2 are
      differentially regulated in the TCR-signaling pathway and play different
      functions.

PMID- 17189709
TI  - Metabolic engineering with a morphine biosynthetic P450 in opium poppy surpasses
      breeding.
AB  - Morphine biosynthesis was genetically engineered in an industrial elite line of
      the opium poppy (Papaver somniferum L.), to modify the production of alkaloids in
      plants. The cytochrome P-450-dependent monooxygenase (S)-N-methylcoclaurine 3'
      hydroxylase (CYP80B3) lies on the pathway to the benzylisoquinoline alkaloid
      branch point intermediate (S)-reticuline. Overexpression of cyp80b3 cDNA resulted
      in an up to 450% increase in the amount of total alkaloid in latex. This increase
      occurred either without changing the ratio of the individual alkaloids, or
      together with an overall increase in the ratio of morphine. Correspondingly,
      antisense-cyp80b3 cDNA expressed in opium poppy caused a reduction of total
      alkaloid in latex up to 84%, suggesting that the observed phenotypes were
      dependent on the presence of the transgene. This study found compelling evidence,
      that cyp80b3 is a key regulation step in morphine biosynthesis and provides
      practical means to genetically engineer valuable secondary metabolites in this
      important medicinal plant.

PMID- 17189710
TI  - Tension band stabilisation of acetabular physeal fractures in four kittens.
AB  - The surgical repair of acetabular physeal fractures in four kittens using a screw
      and tension band technique is reported. This was an appropriate method for
      restoring articular congruency and improving pelvic alignment. All cases had an
      excellent outcome and full limb use following fracture repair. In kittens younger
      than 12 weeks, there is a possibility of premature fusion of the acetabular bone
      resulting in development of a deformed, shallow acetabulum and hip subluxation.
      However, surgery is still justified when there is pelvic canal narrowing to
      decrease the risk of future defecatory problems. Early implant removal in such
      young kittens may decrease the severity of deformity caused by premature physeal
      closure. In kittens of 16 weeks or older, the prognosis is good for normal
      acetabular development and implant removal is not necessary.

PMID- 17189712
TI  - Site-specific protein modification: advances and applications.
AB  - Although chemical methods to modify proteins in a sequence-specific manner have
      yet to be developed, site-specific post-translational modification of proteins
      has recently emerged as a major focus in biological chemistry. Post-translational
      modification with functionalized substrate analogues opens up several unique
      avenues to induce selective reactivity into proteins in a sequence-specific
      manner, and can be applied to protein identification and manipulation in both in
      vitro and in vivo contexts. Further in vivo applications of this method will
      enable the imaging of cellular processes, avoiding nonspecific labeling and probe
      scattering, major complications observed in nonenzymatic methods. Additionally,
      new tools for in vitro protein modification have been developed that offer more
      versatile ways to study protein structure and function.

PMID- 17189711
TI  - Manual fixation versus locking during upper cervical segmental mobilization. Part
      2: an in vitro three-dimensional arthrokinematic analysis of manual axial
      rotation and lateral bending mobilization of the atlanto-axial joint.
AB  - BACKGROUND: Three-dimensional kinematic aspects of coupled motion during manual
      cervical mobilization have not previously been studied. Using an in vitro 3D
      motion analysis method, the kinematic effects of two different segmental
      techniques for axial rotation and lateral bending mobilization of the upper
      cervical spine were investigated as a second part of the study (in part one,
      kinematic effects of flexion-extension mobilization have been investigated).
      METHODS: Axial rotation and lateral bending mobilization of the atlanto-occipital
      and atlanto-axial segments were analysed in vitro using an electromagnetic
      tracking device. Local reference frames were defined based on bony reference
      points that were registered using a 3D-digitizing stylus. Five embalmed and one
      fresh specimen were analysed. Segmental motion was registered simultaneously in
      the atlanto-occipital and the atlanto-axial joints during manual mobilization
      through the full range of axial rotation and lateral bending mobility. The 3D
      kinematic aspects during regional mobilization were compared with those during
      segmental mobilization with manual fixation and during segmental mobilization
      using a locking technique. RESULTS: During both segmental axial rotation
      techniques of the atlanto-axial joint, a significant reduction of the coupled
      lateral bending and flexion-extension motion was observed. The locking technique
      also induced an increase in the main axial rotation component. During lateral
      bending mobilization of the atlanto-axial joint, the manual fixation technique
      reduced the effect on the coupled flexion-extension component significantly.
      INTERPRETATIONS: These results suggest that for manual segmental axial rotation
      and lateral bending mobilization of the upper cervical spine segmental manual
      fixation or locking may be preferred in different situations depending on the
      desired effects. This study brings additional information to the data provided by
      part 1 of this study on the 3D-arthrokinematic effects of flexion-extension
      mobilization.

PMID- 17189713
TI  - Double-label expression studies of prostacyclin synthase, thromboxane synthase
      and COX isoforms in normal aortic endothelium.
AB  - We have performed double-label immunofluorescence microscopy studies to evaluate
      the extent of co-localization of prostacyclin synthase (PGIS) and thromboxane
      synthase (TXS) with cyclooxygenase (COX)-1 and COX-2 in normal aortic
      endothelium. In dogs, COX-2 expression was found to be restricted to small foci
      of endothelial cells while COX-1, PGIS and TXS were widely distributed throughout
      the endothelium. Quantification of the total cross-sectioned aortic endothelium
      revealed a 6- to 7-fold greater expression of COX-1 relative to COX-2 (55 vs. 8%)
      and greater co-distribution of PGIS with COX-1 compared to COX-2 (19 vs. 3%).
      These results are in contrast to the extensive co-localization of PGIS and COX-2
      in bronchiolar epithelium. In rat and human aortas, immunofluorescence studies
      also showed significant COX-1 and PGIS co-localization in the endothelium. Only
      minor focal COX-2 expression was detected in rat endothelium, similar to the dog,
      while COX-2 was not detected in human specimens. Inhibition studies in rats
      showed that selective COX-1 inhibition caused a marked reduction of 6-keto
      PGF(1alpha) and TXB(2) aortic tissue levels, while COX-2 inhibition had no
      significant effect, providing further evidence for a functionally larger
      contribution of COX-1 to the synthesis of prostacyclin and thromboxane in aortic
      tissue. The data suggest a major role for COX-1 in the production of both
      prostacyclin and thromboxane in normal aortic tissue. The extensive co
      localization of PGIS and COX-2 in the lung also indicates significant tissue
      differences in the co-expression patterns of these two enzymes.

PMID- 17189714
TI  - EAE laboratory standards and accreditation.
AB  - Laboratory standards have been set by the European Association of
      Echocardiography of the European Society of Cardiology, in order to homogenize
      the practice of echocardiography in Europe and therefore ultimately, to protect
      patients. These standards have been developed for transthoracic, transesophageal
      and stress Echocardiography into two levels; the basic level, set to provide
      basic laboratory standards for an optimal clinical service and the advanced
      level, which is set to establish a fewer number of advanced laboratories in each
      country, where by in addition to basic standards, they may be providing extensive
      teaching and research.

PMID- 17189716
TI  - Aneuploidy acts both oncogenically and as a tumor suppressor.
AB  - An abnormal chromosome number, aneuploidy, is a common characteristic of tumor
      cells. Boveri proposed nearly 100 years ago that aneuploidy causes tumorigenesis,
      but this has remained untested due to the difficulty of selectively generating
      aneuploidy. Cells and mice with reduced levels of the mitosis-specific,
      centromere-linked motor protein CENP-E are now shown to develop aneuploidy and
      chromosomal instability in vitro and in vivo. An increased rate of aneuploidy
      does drive an elevated level of spontaneous lymphomas and lung tumors in aged
      animals. Remarkably, however, in examples of chemically or genetically induced
      tumor formation, an increased rate of aneuploidy is a more effective inhibitor
      than initiator of tumorigenesis. These findings reveal a role of aneuploidy and
      chromosomal instability in preventing tumorigenesis.

PMID- 17189715
TI  - Mad2 overexpression promotes aneuploidy and tumorigenesis in mice.
AB  - Mad2 is an essential component of the spindle checkpoint that blocks activation
      of Separase and dissolution of sister chromatids until microtubule attachment to
      kinetochores is complete. We show here that overexpression of Mad2 in transgenic
      mice leads to a wide variety of neoplasias, appearance of broken chromosomes,
      anaphase bridges, and whole-chromosome gains and losses, as well as acceleration
      of myc-induced lymphomagenesis. Moreover, continued overexpression of Mad2 is not
      required for tumor maintenance, unlike the majority of oncogenes studied to date.
      These results demonstrate that transient Mad2 overexpression and chromosome
      instability can be an important stimulus in the initiation and progression of
      different cancer subtypes.

PMID- 17189717
TI  - Role of two active site Glu residues in the molecular action of botulinum
      neurotoxin endopeptidase.
AB  - Botulinum neurotoxin type A (BoNT/A) light chain (LC) is a zinc endopeptidase
      that causes neuroparalysis by blocking neurotransmitter release at the
      neuromuscular junctions. The X-ray crystal structure of the toxin reveals that
      His223 and His227 of the Zn(2+) binding motif HEXXH directly coordinate the
      active site zinc. Two Glu residues (Glu224 and Glu262) are also part of the
      active site, with Glu224 coordinating the zinc via a water molecule whereas
      Glu262 coordinates the zinc directly as the fourth ligand. In the past we have
      investigated the topographical role of Glu224 by replacing it with Asp thus
      reducing the side chain length by 1.4 A that reduced the endopeptidase activity
      dramatically [L. Li, T. Binz, H. Niemann, and B.R. Singh, Probing the role of
      glutamate residue in the zinc-binding motif of type A botulinum neurotoxin light
      chain, Biochemistry 39 (2000) 2399-2405]. In this study we have moved the Glu 224
      laterally by a residue (HXEXH) to assess its positional influence on the
      endopeptidase activity, which was completely lost. The functional implication of
      Glu262 was investigated by replacing this residue with aspartate and glutamine
      using site-directed mutagenesis. Substitution of Glu262 with Asp resulted in a 3
      fold decrease in catalytic efficiency. This mutation did not induce any
      significant structural alterations in the active site and did not interfere with
      substrate binding. Substitution of Glu262 with Gln however, dramatically impaired
      the enzymatic activity and this is accompanied by global alterations in the
      active site conformation in terms of topography of aromatic amino acid residues,
      zinc binding, and substrate binding, resulting from the weakened interaction
      between the active site zinc and Gln. These results suggest a pivotal role of the
      negatively charged carboxyl group of Glu262 which may play a critical role in
      enhancing the stability of the active site with strong interaction with zinc. The
      zinc may thus play structural role in addition to its catalytic role.

PMID- 17189718
TI  - Nutrition.

PMID- 17189719
TI  - Special circumstances: trophic feeds, necrotizing enterocolitis and
      bronchopulmonary dysplasia.
AB  - There are many unresolved issues regarding how to feed the extremely-low-birth
      weight (ELBW) infant. Trophic feedings of small volumes of breast milk or formula
      do not appear to increase the incidence of necrotizing enterocolitis (NEC). For
      prevention of NEC, breast milk, antenatal steroids and fluid restriction each
      confers a benefit. Because the incidence of NEC is relatively low, to determine
      if a particular prevention strategy is effective, large numbers of infants would
      need to be enrolled in a prospective, randomized controlled trial, and such
      trials are rare. Candidate therapies for NEC prevention that warrant further
      study include oral immunoglobulins, probiotics, long-chain polyunsaturated fatty
      acids and arginine. Suboptimal nutrition in ELBW infants is common in the early
      postnatal period. This is also the most critical time for the development of
      bronchopulmonary dysplasia, when even brief periods of malnutrition have
      significant effects on lung development and growth.

PMID- 17189737
TI  - Postnatal psychiatric morbidity: a validation study of the GHQ-12 and the EPDS as
      screening tools.
AB  - OBJECTIVE: To assess the validity of the 12-Item General Health Questionnaire
      (GHQ-12) and the Edinburgh Postnatal Depression Scale (EPDS) in screening for the
      most common postnatal psychiatric morbidities (mood, anxiety and adjustment
      disorders). METHOD: A two-phase cross-sectional study was designed. First, a
      sample of 1453 women visiting at 6 weeks postpartum completed the GHQ-12 and the
      EPDS questionnaires. Second, based upon EPDS outcomes, participants were
      stratified and randomly selected within each stratum for clinical evaluation
      [Structured Clinical Interview for DSM-IV (SCID)]. Receiver operating
      characteristic (ROC) analysis was used. RESULTS: The concurrent validity was
      satisfactory (0.80). At optimum cut-off scores, both GHQ-12 and EPDS yielded very
      good sensitivity (80; 85.5) and specificity (80.4; 85.3), respectively. ROC
      curves showed that the performance of the EPDS (AUC=0.933) is slightly superior
      to that of GHQ-12 (AUC=0.904). CONCLUSION: Both GHQ-12 and EPDS are valid
      instruments to detect postnatal depression as well as postnatal anxiety and
      adjustment disorders.

PMID- 17189721
TI  - Role of heterodimerization of c-Fos and Fra1 proteins in osteoclast
      differentiation.
AB  - Bone resorbing osteoclasts are specialized macrophages that cannot differentiate
      in the absence of c-Fos, a member of the dimeric transcription factor AP-1
      (activator protein-1). However, osteoclast differentiation in the absence of c
      Fos can be rescued in vitro and in vivo by Fra1, a Fos-like protein and
      transcriptional target of c-Fos. To enable AP-1 proteins binding to DNA, c-Fos or
      Fra1 must heterodimerize with a partner such as c-Jun, JunB and JunD. In this
      study, we investigated the dimerization partners of c-Fos and Fra1 required for
      osteoclast differentiation using synthetic "single-chain" AP-1 dimers in which c
      Fos or Fra1 is tethered via a linker to Jun proteins. When c-Fos was analyzed in
      combination with any Jun protein, including a c-Jun mutant lacking major
      phosphorylation sites for c-Jun amino-terminal kinase (JNK), osteoclasts were
      efficiently formed from c-Fos-deficient hematopoietic precursors. However, Fra1
      in combination with any Jun protein could not rescue osteoclastogenesis. The
      ability to rescue was compared to transcriptional activity measured in transient
      transfection assays using promoters driven by consensus AP-1 sites or a composite
      AP-1/NFAT binding site. These data show that a single Jun/c-Fos dimer is
      sufficient for osteoclast differentiation, likely due to its transactivation
      ability for a broader range of promoters, in particular consensus AP-1 sites. We
      propose that Fra1 together with a dimerization partner different from Jun
      proteins can rescue osteoclast differentiation in c-Fos-deficient precursors.

PMID- 17189738
TI  - A brief two-item screener for detecting a history of physical or sexual abuse in
      childhood.
AB  - BACKGROUND: A number of medical practice guidelines and recommendations call for
      screening adult patients for a history of physical or sexual abuse in childhood,
      but no brief screening tools exist. The objective of this study was to assess the
      accuracy of a two-item screener for physical or sexual abuse in childhood.
      METHODS: This is a cross-sectional study of randomly selected women (aged 18-65
      years) from a large health maintenance organization. One thousand two hundred
      twenty-five patients were administered a questionnaire, which included two items
      in a brief screener: (a) "When I was growing up, people in my family hit me so
      hard that it left me with bruises or marks" and (b) "When I was growing up,
      someone tried to touch me in a sexual way or tried to make me touch them." A
      subset of 216 patients completed a semistructured interview for a history of
      physical or sexual abuse in childhood. RESULTS: The two-item screener was
      sensitive (84.8%) and specific (88.1%) for detecting a history of physical or
      sexual abuse in childhood, as determined by the semistructured interview.
      CONCLUSIONS: The two-item screener provides an accurate tool, which is easily
      integrated into a comprehensive health questionnaire or administered verbally by
      a clinician, to assess for history of abuse.

PMID- 17189739
TI  - Depression in burn reconstruction patients: symptom prevalence and association
      with body image dissatisfaction and physical function.
AB  - OBJECTIVE: This study investigated the prevalence and the clinical correlates of
      symptoms of depression among burn reconstruction patients. METHOD: A sample of
      224 burn reconstruction patients completed the Beck Depression Inventory (BDI),
      the SF-36 Health Survey and the Satisfaction with Appearance Scale. RESULTS: The
      prevalence of at least mild to moderate symptoms of depression (BDI > or =10) was
      46%. Female patients were disproportionately represented in this burn
      reconstruction population (46%) compared to all survivors from the burn center
      (29%; P<.001) and compared to a national sample of burn survivors (27%; P<.001).
      Compared to males, female patients presented for consultation much longer after a
      burn injury (P<.001), tended to have smaller burns (P=.06) and were less likely
      to have facial burns (P=.08). Depressive symptoms were largely predicted by body
      image dissatisfaction (beta=.58; P<.001), with additional variance predicted by
      physical function (beta=-.13; P=.07). The effect of patient and burn injury
      variables on depressive symptoms was mediated by body image dissatisfaction and
      physical function. CONCLUSION: The high prevalence of significant symptoms of
      depression in burn reconstruction patients and their relationship with body image
      suggest the importance of the routine psychological screening of patients seeking
      reconstruction services.

PMID- 17189720
TI  - Evolving gene therapy approaches for osteosarcoma using viral vectors: review.
AB  - This review begins with an introduction to the malignant bone tumor, osteosarcoma
      [OS] and then moves to a discussion of the commonly used vectors for gene
      transfer. We first briefly highlight non-viral vectors including polymeric and
      liposomal delivery systems but concentrate predominantly on the 5 leading viral
      vectors used in cancer gene therapy, specifically retroviruses, adeno-associated
      viruses, herpes viruses and lentiviruses with the most detailed analysis reserved
      for adenoviruses. The 3 main strategies for gene therapy in osteosarcoma are next
      summarized. As part of this review, the several prodrug-converting enzymes
      utilized in OS suicide gene therapy are examined. The text then turns to a
      discussion of adenovirus-mediated gene transfer and the need for tumor targeting
      via transductional or transcriptional approaches. Because of practical problems
      with use of replication-incompetent viruses in achieving complete tumor kill in
      vivo, virotherapy utilizing replication competent viruses has come to the fore.
      This topic is, thus, next reviewed which allows for a natural transition to a
      discussion of armed therapeutic viruses many of which are conditionally
      replicating adenoviruses carrying transgenes with established anti-tumor
      efficacy. We recognize that several other issues have arisen which hamper
      progress in the field of cancer gene therapy. We, therefore, review viral-induced
      toxicity in the host and vector delivery issues which have been found to
      potentially influence safety. We end with a brief perspective including
      commenting on animal models used in examining delivery strategies for
      osteosarcoma gene therapy. The challenges remaining are touched upon most
      especially the need to deal with pulmonary metastatic disease from OS.

PMID- 17189740
TI  - Quality of life in patients with Behcet's disease: the impact of major
      depression.
AB  - OBJECTIVE: Behcet's disease (BD) is a multisystemic inflammatory disorder
      associated with high levels of depressive symptoms and lower quality of life
      (QoL). In this study, we aimed to investigate the impact of major depression (MD)
      on the QoL of patients with BD. METHOD: BD outpatients (n=25) and psychiatric
      outpatients (n=25) with only MD among the Axis I psychiatric disorders, and BD
      outpatients (n=25) and healthy controls (n=25) without any Axis I psychiatric
      disorder were included in the study. The Structured Clinical Interview for DSM-IV
      (SCID-I) was used to determine Axis I psychiatric disorders. Depression and QoL
      levels were assessed with the Beck Depression Inventory (BDI) and the World
      Health Organization QoL Assessment-Brief (WHOQOL-BREF), respectively. RESULTS:
      There was no significant difference with regard to demographic characteristics
      between the groups. Psychiatric and BD patients with MD had significantly lower
      overall WHOQOL-BREF subscale scores than BD patients without MD and healthy
      controls. No significant difference was found in terms of QoL between the groups
      of psychiatric and BD patients with MD, nor between the groups of BD patients
      without MD and healthy controls. Overall, there was a significantly negative
      correlation between all WHOQOL-BREF subscale and BDI scores in BD patients.
      CONCLUSION: The study suggests that concurrent MD has a negative impact on QoL of
      BD patients and that QoL is negatively correlated with the severity of depressive
      symptoms.

PMID- 17189741
TI  - Prevalence and treatment of depression in a hospital department of internal
      medicine.
AB  - BACKGROUND: Depressive disorders are overrepresented among patients admitted to
      nonpsychiatric units of general hospitals, but the majority of depressed patients
      are not identified in this setting. Effective and well-tolerated treatments and
      reliable diagnostic criteria, together with new assessment tools (self
      administered or not), have been developed with encouraging results. Nevertheless,
      few studies have utilized standardized instruments and extensive clinical
      interviews by well-trained psychiatrists to assess depression. New research
      should test these tools in a French-speaking environment. METHODS: The
      investigation covered 292 patients aged 18-65 who were admitted over a period of
      6 months to the internal medicine units of Geneva University Hospitals. Each
      patient filled in a self-administered questionnaire for depression [Patient
      Health Questionnaire (PHQ-9)]; 212 patients were also evaluated by a psychiatrist
      using DSM-IV diagnostic assessment and the Hamilton Depression Rating Scale
      during the first week of their hospital stay; both assessments were single
      blinded. RESULTS: Psychiatric clinical interviews identified a high proportion
      (26.9%) of depressive disorders (37% among women) for all diagnoses; 11.3% (17.3%
      among women) of the patients met the DSM-IV criteria for major depression. The
      PHQ-9 identified depressive disorders among 34.9% of patients (42% among women)
      and identified a major depressive syndrome among 18.4% of patients (29.6% among
      women). Physicians in the internal medicine unit identified only about half the
      depressive patients; at the time of psychiatric examination, fewer than one in
      four patients was receiving antidepressant therapy. CONCLUSIONS: Our findings
      confirm the results of previous investigations, which showed that the failure to
      detect and treat depression is a major health problem among patients admitted to
      nonpsychiatric units of a general hospital.

PMID- 17189742
TI  - Looming threat-processing style in a cancer cohort.
AB  - OBJECTIVE: Looming threat-processing style, where threats are perceived to be
      progressing (looming) at a frightening velocity, is implicated in anxiety
      vulnerability. This study aims to validate a new measure of looming, the looming
      cancer, and explore its clinical correlates in a chronic lymphocytic leukemia
      (CLL) cohort. METHODS: In a cross-sectional design, 105 CLL patients completed
      the Looming Cancer Scale, Looming Cognitive Style Questionnaire (LCSQ), SF-36,
      Beck Anxiety Inventory (BAI) and Beck Depression Inventory II (BDI-II). RESULTS:
      Exploratory factor analysis reduced the 20-item Looming Cancer Scale to a 10-item
      version, which demonstrated good psychometric properties (Cronbach's alpha=.926).
      Convergent validity was demonstrated by Pearson correlation with the LCSQ
      (0.418), BAI (0.380), BDI-II (0.336) and the mental component score of the SF-36
      (-0.434) (all P<.001). Divergent validity was demonstrated by a lack of
      correlation with the SF-36 physical component score and cross tabulation
      frequencies of high and low loomers. High vs. low loomers showed significantly
      more anxiety (31% vs. 13%), depression (23% vs. 2%) and mixed anxiety-depression
      (18% vs. 2%). An area under the receiver operating characteristic curve analysis
      revealed high sensitivity (82%) and specificity (69%) in detecting mixed anxiety
      depression using a cutoff score of >/=20/30. CONCLUSIONS: The Looming Cancer
      Scale is a valid measurement of looming cognitive style and is the first time
      that the looming construct has been studied in a cancer cohort. The importance of
      this research lies in its potential to identify populations vulnerable to
      developing anxiety, depression and mixed anxiety-depression symptoms.

PMID- 17189743
TI  - Emergency management of agitation in pregnancy.
AB  - OBJECTIVE: This study aimed to better understand how agitated pregnant women are
      pharmacologically managed in a psychiatric emergency service (PES). METHOD: A
      retrospective chart review was conducted on 80 women admitted to a PES with HCG
      positive urine, from January 1, 2004, to June 30, 2005. Of these, 31 patients
      required medication for agitation. We describe the demographics (age, ethnicity,
      housing status, insurance status), chief complaint, medical status, drug use and
      medical management in the PES, as well as pregnancy awareness, prenatal care and
      trimester. Patient data were analyzed using simple frequency calculations and
      cross tabulations with SPSS. RESULTS: Thirty-one (39%) patients received 34 doses
      of psychotropic medication. Haloperidol, alone or in combination with a
      benzodiazepine, was the most frequently administered psychotropic medication,
      while risperidone was the second most commonly administered medication. Two
      patients required brief restraint for assaultive behavior that was unresponsive
      to any other intervention. CONCLUSION: There are algorithms that provide guidance
      to clinicians regarding the pharmacological management of aggression. However,
      there are no efficacy or safety studies that recommend strategies for the
      management of the agitated pregnant patient.

PMID- 17189744
TI  - Violent behavior of patients admitted in emergency following drug suicidal
      attempt: a specific staff educational crisis intervention.
AB  - OBJECTIVE: In spite of much effort to create guidelines on the management of
      violent behavior (VB) in emergency departments, little is known about the impact
      of such guidelines on a real-life emergency environment. The aim of this study is
      to investigate the impact of a staff educational crisis intervention (SECI) on
      the reduction of VB in patients admitted to emergency departments following drug
      suicidal attempt. METHOD: The impact of a SECI on VB of patient consulting the ER
      following a drug suicide attempt was assessed by comparing the occurrence of VB
      before (5 months) and after (5 months) the introduction of a SECI. RESULTS: A
      significant reduction in VB (from 17.32% to 7.14%) was found with the comparison
      of two 5-month periods: before (254 patients) and after (224 patients) the
      introduction of a SECI program (chi(2)=11.238; P=.0008). CONCLUSION: These
      preliminary data suggest the need for further prospective randomized studies
      aiming to prevent VB in emergency departments by developing specific SECI
      programs.

PMID- 17189745
TI  - Dissociative disorders in the psychiatric emergency ward.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of dissociative
      disorders among emergency psychiatric admissions. METHOD: Forty-three of the 97
      consecutive outpatients admitted to the psychiatric emergency unit of a
      university hospital were screened using the Dissociative Experiences Scale (DES).
      Seventeen (39.5% of the 43 evaluated) patients with a DES score above 25.0 were
      then interviewed with the Dissociative Disorders Interview Schedule and the
      Structured Clinical Interview for Dissociative Disorders. RESULTS: Fifteen
      emergency unit patients (34.9% of the 43 evaluated participants) were diagnosed
      as having a dissociative disorder. Six (14.0%) patients had dissociative identity
      disorder, 6 (14.0%) had dissociative disorder not otherwise specified, and 3
      (7.0%) had dissociative amnesia. The average DES score of dissociative patients
      was 43.7. A majority of them had comorbid major depression, somatization
      disorder, and borderline personality disorder. Most of the patients with
      dissociative disorder reported auditory hallucinations, symptoms associated with
      psychogenic amnesia, flashback experiences, and childhood abuse and/or neglect.
      CONCLUSIONS: Dissociative disorders constitute one of the diagnostic groups with
      high relevance in emergency psychiatry.

PMID- 17189746
TI  - Intramuscular olanzapine in patients with borderline personality disorder: an
      observational study in an emergency room.
AB  - OBJECTIVE: Despite the frequency of borderline personality disorder (BPD) in
      patients with acute agitation in emergency departments (EDs), there are few data
      about the use of intramuscular (IM) psychotropics in those patients. This is the
      first open-label study with olanzapine in this setting. METHOD: Measures were
      collected prospectively for patients with acute agitation in ED. Consent was
      obtained subsequently and diagnosis ascertained using the Structured Clinical
      Interview for DSM-IV. A group of 25 patients with severe agitation and BPD
      received olanzapine 10 mg IM. Efficacy and safety data are available at baseline,
      2 h postinjection and at discharge. RESULTS: Significant reductions of agitation
      associated with good tolerance were observed 2 h after the first IM olanzapine.
      Sixteen percent of patients required a second IM olanzapine. CONCLUSIONS:
      Randomized, placebo-controlled studies are needed to confirm the efficacy of IM
      olanzapine in patients with acute agitation and BPD.

PMID- 17189747
TI  - Do psychiatric patients improve their competency to consent to hospitalization
      after admission? A prospective study in an acute inpatient ward.
AB  - OBJECTIVES: Competency to consent to hospitalization has important clinical and
      ethical implications. However, there are no follow-up studies that evaluate
      improvement in competency during psychiatric hospitalization. The authors sought
      to determine whether patients admitted to a psychiatric ward as incompetent to
      consent to hospitalization improve their competency during hospitalization.
      METHOD: A total of 160 consecutively admitted patients were administered the
      Competency Questionnaire (CQ), a structured scale designed to assess competency
      to consent to psychiatric hospitalization. The CQ was administered both upon
      admission and at discharge. Severity and acuity of the psychiatric disorder were
      assessed with the Severity of Psychiatric Illness Scale and the Acuity of
      Psychiatric Illness Scale. RESULTS: Of the 160 assessed patients, 70 (43.8%) were
      rated incompetent. Forty-five of these 70 incompetent patients completed the
      admission-to-discharge follow-up. Twenty-one of these 45 patients (46.6%)
      remained incompetent at discharge. Participation in the treatment process was the
      only variable that predicted improvement on competency during hospitalization.
      Severity of psychiatric illness at admission did not predict improvement on
      competency. CONCLUSIONS: Nearly half of the patients who upon admission were
      incompetent remained incompetent at discharge.

PMID- 17189748
TI  - Psychiatric hospitalizations during the last 12 months before suicide.
AB  - OBJECTIVES: Suicide victims frequently have had contact with the mental health
      care system before they died. In this study, the rates, numbers and lengths of
      psychiatric hospitalizations of suicide victims during the last year before their
      suicide commission were assessed. METHODS: The quarterly and monthly
      hospitalization rates during the last 12 months of 665 individuals who committed
      suicide were compared. RESULTS: Of the suicide victims, 16.4% had been
      hospitalized at least once. The period after a recent discharge bore the highest
      risk for suicide commission, with 4.7% (28.4% of those hospitalized) committing
      suicide within 1 week after their discharge and 7.8% (47.7%) committing suicide
      within 1 month. Hospitalization rates were significantly higher in the last 3
      months as compared with the preceding quarters. CONCLUSION: Increasing
      utilization of inpatient treatment facilities should prompt a particularly
      profound suicide risk assessment and postdischarge treatment planning.

PMID- 17189749
TI  - Heart rate as a predictor of posttraumatic stress disorder in children.
AB  - OBJECTIVE: This study indexed the relationship between resting heart rates (HRs)
      after injury and subsequent posttraumatic stress disorder (PTSD) in children.
      METHOD: Children aged between 7 and 12 years who were hospitalized after
      traumatic injury (n=76) had their resting HR assessed after injury and were
      assessed for PTSD 6 months after injury (n=62). RESULTS: Full/subsyndromal PTSD
      was diagnosed in 27% of children. Children with full/subsyndromal PTSD had higher
      HRs after trauma than those without PTSD. Children with an elevated HR were more
      likely to develop PTSD after controlling for age, sex and injury severity
      (adjusted odds ratio=5.89). CONCLUSIONS: These findings accord with the proposal
      that fear conditioning shortly after trauma contributes to PTSD in children.

PMID- 17189750
TI  - Pregnancy and malignant catatonia.
AB  - The occurrence of malignant catatonia in pregnancy is a psychiatric emergency. In
      this article, we present the case of a pregnant woman with a first psychotic
      episode with catatonic features, autonomic abnormalities and elevated creatinine
      phosphokinase levels in the context of a severe adverse reaction to antipsychotic
      pharmacotherapy who had good responses to electroconvulsive therapy and
      lorazepam.

PMID- 17189751
TI  - Restless legs syndrome induced by citalopram: a psychiatric emergency?
AB  - OBJECTIVE: The objective of this case report is to create awareness on restless
      legs syndrome (RLS) among clinicians working in emergency units. METHOD: We
      describe a case reporting important aggravation of RLS associated with
      citalopram, 60 mg/day, in a 48-year-old woman who was sent to the emergency unit
      by her general practitioner. Citalopram was replaced by bupropion, 150 mg/day,
      and sertraline, 50 mg/day. RESULTS: Three days later, symptoms of RLS started to
      diminish and, after 3 weeks, clinical symptoms had disappeared entirely. On 6
      month follow-up, the patient did not manifest clinically significant RLS.
      Ignoring RLS could lead to a worsening of symptoms and could increase the risk
      for iatrogenic conditions. The prevalence of RLS in the general population is 3
      9%; nevertheless, this syndrome is frequently underdiagnosed. CONCLUSION: This
      case report suggests that RLS could be considered as a possible "dopamine
      dependent side effect" of selective serotonin reuptake inhibitors (SSRIs).
      Bupropion could potentially "correct" dopaminergic dysfunction in RLS, and
      sertraline appears to be the SSRI that provides the least risk of RLS by blocking
      dopamine reuptake.

PMID- 17189753
TI  - Clozapine-induced angioneurotic edema.
AB  - Many prescribed drugs can cause cutaneous rashes and eruptions, which may present
      in various forms and severity. Most of these reactions are mild; however, the
      severe cases can lead to life-threatening complications. The most severe of these
      reactions may include angioedema, acute generalized exanthematous reactions,
      Stevens-Johnson syndrome and toxic epidermal necrolysis. We report two cases
      wherein the patients developed classical angioneurotic edema on clozapine therapy
      and improved rapidly when clozapine was stopped.

PMID- 17189752
TI  - Olanzapine-induced agranulocytosis in systemic lupus erythematosus: a case
      report.
AB  - Systemic lupus erythematosus (SLE) patients may have psychiatric manifestations
      during the illness course. Psychotropic agents are indicated in treating these
      symptoms. Second-generation antipsychotics, such as risperidone, olanzapine and
      quetiapine, have been thought to be safer than clozapine with regard to the side
      effect of neutropenia or agranulocytosis. We report a case of SLE who developed
      agranulocytosis during the treatment with olanzapine for the SLE-related
      psychiatric symptoms.

PMID- 17189755
TI  - Isoniazid-associated psychosis.

PMID- 17189756
TI  - The growth of Propionibacterium cyclohexanicum in fruit juices and its survival
      following elevated temperature treatments.
AB  - This study investigated the growth of Propionibacterium cyclohexanicum in orange
      juice over a temperature range from 4 to 40 degrees C and its ability to multiply
      in tomato, grapefruit, apple, pineapple and cranberry juices at 30 and 35 degrees
      C. Survival after 10 min exposure to 50, 60, 70, 80, 85, 90 and 95 degrees C in
      culture medium and in orange juice was also assessed. In orange juice the
      organism was able to multiply by 2 logs at temperatures from 4 to 35 degrees C
      and survived for up to 52 days. However, at 40 degrees C viable counts were
      reduced after 6 days and no viable cells isolated after 17 days. The optimum
      growth temperature in orange juice over 6 days was 25 degrees C but over 4 days
      it was 35 degrees C. The growth of P. cyclohexanicum was monitored in tomato,
      grapefruit, cranberry, pineapple and apple juices at 30 and 35 degrees C over 29
      days. Cranberry, grapefruit and apple juice did not support the growth of P.
      cyclohexanicum. At 30 degrees C no viable cells were detected after 8 days in
      cranberry juice or after 22 days in grapefruit juice while at 35 degrees C no
      viable cells were detected after 5 and 15 days, respectively. However, in apple
      juice, although a 5 log reduction occurred, viable cells could be detected after
      29 days. P. cyclohexanicum was able to multiply in both tomato and pineapple
      juices. In tomato juice, there was a 2 log increase in viable counts after 8 days
      at 30 degrees C but no increase at 35 degrees C, while in pineapple juice there
      was a 1 log increase in numbers over 29 days with no significant difference
      between numbers of viable cells present at 30 and 35 degrees C. The organism
      survived at 50 degrees C for 10 min in culture medium without a significant loss
      of viability while similar treatment at 60, 70 and 80 degrees C resulted in
      approximately a 3-4 log reduction, with no viable cells detected after treatment
      at 85 or 90 or 95 degrees C but, when pre-treated at intermediate temperatures
      before exposure to higher temperatures, some cells survived. However, in orange
      juice a proportion of cells survived at 95 degrees C for 10 min without pre
      treatment and there was no significant difference between numbers surviving with
      and without pre-treatment. The results from this study demonstrate that P.
      cyclohexanicum is able to grow in a number of juices, other than orange juice,
      and able to survive a number of high temperature procedures. Therefore, if
      initially present in the raw materials P. cyclohexanicum might survive the
      pasteurization procedures used in the fruit juice industry, contaminate and
      consequently spoil the final product.

PMID- 17189754
TI  - Syndrome of inappropriate secretion of antidiuretic hormone due to citalopram and
      venlafaxine.
AB  - INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine are
      often used to treat depression in the elderly due to their low incidence of side
      effects. All five of the SSRIs currently available and venlafaxine have been
      associated with hyponatremia. CASE REPORT: This article describes the case of an
      87-year-old man with depression who presented with hyponatremia after starting
      treatment with citalopram. After excluding other common causes of hyponatremia, a
      diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
      was confirmed. Sodium levels returned to the normal range following
      discontinuation of citalopram. Subsequently, due to the persistence of
      depression, treatment with venlafaxine was initiated. Three weeks later,
      hyponatremia associated with SIADH was once again diagnosed and venlafaxine was
      discontinued. The hyponatremia resolved in 2 weeks. DISCUSSION: Both SSRIs and
      venlafaxine have been associated with SIADH in numerous case reports and
      retrospective studies. Risk factors for developing hyponatremia with these drugs
      are advanced age and treatment with other medications. To our knowledge, this is
      the first case report in which SIADH was associated with two different families
      of antidepressants in the same patient. CONCLUSION: Physicians should be aware of
      the risk of hyponatremia when prescribing SSRIs and venlafaxine in elderly
      patients with multiple drug therapies. Sodium levels should be monitored during
      treatment.

PMID- 17189757
TI  - Ochratoxin A in red paprika: relationship with the origin of the raw material.
AB  - The occurrence of ochratoxin A (OA) in paprika elaborated from peppers grown in
      several countries (Peru, Brazil, Zimbabwe and Spain) was studied, using an
      immunoaffinity clean-up column coupled to liquid chromatography and fluorescence
      detection. The preparation of the methyl ester (OA-Me) and liquid chromatography
      electrospray-ion trap-mass spectrometry was used both to confirm the identity of
      the chromatographic peak that correspond to OA and to quantify it at low levels
      or in dirty fractions. A total of 115 strains of moulds were isolated; 85 of the
      fungal strains were obtained from OA contaminated paprika samples and identified
      as belonging to the Aspergillus Section Circumdati group (A. ochraceus) and
      Section Nigri group (A. niger, A. carbonarius). Among the latter ones, 31% of the
      A. ochraceus isolates and one A. niger were OA producers in vitro. None of the
      mould strains isolated from paprika samples with undetectable levels of OA or
      concentrations below 1 microg kg(-1) were toxin producers. Great differences in
      OA content in paprika samples were found, and a relationship with the climatic
      conditions of the geographic origin of the samples, and with cultural and
      technical practices in pepper manipulation is suggested.

PMID- 17189758
TI  - Modeling the effect of temperature on growth of Salmonella in chicken.
AB  - Growth data of Salmonella in chicken were collected at several isothermal
      conditions (10, 15, 20, 25, 28, 32, 35, 37, 42, and 45 degrees C) and were then
      fitted into primary models, namely the logistic model, modified Gompertz model
      and Baranyi model. Measures of goodness-of-fit such as mean square error, pseudo
      R(2), -2 log likelihood, Akaike's information, and Sawa's Bayesian information
      criteria were used for comparison for these primary models. Based on these
      criteria, modified Gompertz model described growth data the best, followed by the
      Baranyi model, and then the logistic model. The maximum growth rates obtained
      from each primary model were then modeled as a function of temperature using the
      modified Ratkowsky model. Pseudo-R(2) values for this secondary model describing
      growth rate obtained from Baranyi, modified Gompertz, and logistic models were
      0.999, 0.980, and 0.990, respectively. Mean square error values for corresponding
      models were 0.0002, 0.0008, and 0.0009, respectively. Both measures clearly show
      that the Baranyi model performed better than the modified Gompertz model or the
      logistic model.

PMID- 17189759
TI  - Growth kinetics of cultures from single spores of Aspergillus flavus and Fusarium
      verticillioides on yellow dent corn meal.
AB  - A dilution protocol originally developed for the isolation of single bacterial
      cells was modified to suite the specificities of fungal growth. The modified
      protocol was used to study the growth kinetics of single spores of Aspergillus
      flavus and Fusarium verticillioides on yellow dent corn meal. Both a(w) and
      temperature significantly influenced the distributions of the colony growth rates
      and lag phases and the rate at which individual spores of both isolates completed
      the lag period. An interaction between a(w) and temperature was noted on the
      spread of the distributions of these growth parameters. The histograms of the
      single spore colony growth rates and lag phases generally became wider the more
      compromising the conditions for growth became, indicating a greater variation in
      growth ability at these conditions. The rate at which the single spores passed
      through the lag phases generally decreased with decrease in temperature and/or
      a(w), with an interaction again noted between these two factors on the rate.
      These results show the potential range and variability in growth of individual
      fungal spores at the lowest inoculum level possible.

PMID- 17189761
TI  - Effect of preinoculation growth media and fat levels on thermal inactivation of a
      serotype 4b strain of Listeria monocytogenes in frankfurter slurries.
AB  - Preinoculation growth conditions and fat levels were evaluated for effects on the
      heat resistance of Listeria monocytogenes strain MFS 102 in formulated
      frankfurter slurries and on frankfurter surfaces. Comparison of linear
      inactivation rates (D-values) for cells heated in frankfurter slurry showed that
      growth conditions were significant (P<0.05) factors affecting subsequent thermal
      resistance. The average D(60 degrees C)-values for the five preinoculation growth
      media tested from most resistant to least heat resistant were: tryptic soy broth
      with 0.6% yeast extract (TSBYE) (2.2 min) and 8.5% fat slurry (2.2 min), followed
      by 23% fat slurry (1.7 min) and 11% fat slurry (1.7 min), and then TSYBE with
      quaternary ammonium compounds added (TSBYE+Q) (1 min). The fat level in the
      frankfurter heating media also had a significant (P<0.05) effect on the thermal
      death rate of L. monocytogenes. Cells heated in 8.5% fat slurry had a
      significantly higher (P<0.05) D(60 degrees C)-value (2.2 min) than those heated
      in 11% fat (1.0 min) and 23% fat slurry (0.9 min). Growth media (TSBYE, 8.5% fat
      slurry, and TSBYE+Q), and fat level (15% and 20%), however, were not significant
      factors (P>0.05) affecting thermal inactivation rates on frankfurter surfaces.
      Heat inactivation rates were consistently higher on frankfurter surfaces compared
      to similar treatments done in frankfurter slurry. On frankfurter surfaces, a 2.3-
      to 5.1-log(10) reduction was achieved after 15 min depending on frankfurter
      surface type. The time necessary to achieve a 3-log(10) reduction using post
      processing pasteurization of frankfurters in a hot water-bath at 60 degrees C
      almost doubled for cells grown in TSBYE and heated in 23% fat frankfurter slurry
      (19.6 min) versus cells grown and heated in 8.5% fat frankfurter slurry (10.8
      min).

PMID- 17189760
TI  - Identification and characterization of yeast isolated from the elaboration of
      seasoned green table olives.
AB  - The purpose of this study was to investigate the yeast population during the
      processing of green table olives. In the fresh olives, yeast were found at
      concentrations of around 3.0 log cfu/g, with Cryptococcus spp. being predominant.
      In the brine, the yeast concentrations were greater than 4.9 log cfu/ml, with
      Pichia anomala, Kluyveromyces marxianus, and Saccharomyces cerevisiae being the
      predominant species. Unlike the yeast isolated from the fresh olives, the strains
      obtained from the olive brine mostly showed low pectolytic but high catalase
      activities. Some of these strains also exhibited other biochemical desirable
      properties for the fermentation of green table olives, including their lipolytic
      activities and their assimilation or production of organic acids in the brine.
      Seven strains in particular of P. anomala, K. marxianus, S. cerevisiae, and
      Candida maris showed the best properties for use in trials as starter culture in
      pilot fermenters.

PMID- 17189762
TI  - Characterisation of the dominant bacterial population in modified atmosphere
      packaged farmed halibut (Hippoglossus hippoglossus) based on 16S rDNA-DGGE.
AB  - It is not well understood why Atlantic halibut (Hippoglossus hippoglossus) has
      longer shelf-life than most other white fish species. Our approach was to examine
      the microbiological diversity of the spoilage microbiota during modified
      atmosphere (MA) packaging of farmed Atlantic halibut. Portions were packaged with
      gas mixtures of CO(2):N(2) and CO(2):O(2) (50%:50%) and with air as a reference.
      The packages were stored at 4 degrees C and samples were taken 6 times during the
      23 days of storage. Analyses with molecular techniques (PCR-DGGE) determined
      profiles of the bacterial populations in the various samples and sequencing
      detected the bacterial species present. In addition, samples were analysed for
      microbial, chemical and sensory parameters. The shelf-life was 10-13 days when
      stored in air and between 13 and 20 days for MA packages, with oxygen-enriched
      packages suggested as the better gas mixture, based on microbial growth and
      sensory scores. From sequence analyses of the bacterial population Photobacterium
      phosphoreum and Pseudomonas spp. were found to dominate in the halibut.
      Brochothrix thermosphacta was found in most samples at the end of the storage
      period. Shewanella putrefaciens was found sporadically and in low concentrations
      based on microbial methods, but not detected by PCR-DGGE.

PMID- 17189763
TI  - Modelling thermal inactivation of Listeria monocytogenes in sucrose solutions of
      various water activities.
AB  - The heat resistance of Listeria monocytogenes was determined in sucrose solutions
      with water activity (a(w)) ranging from 0.99 to 0.90. At all temperatures
      investigated shape of the survival curves depended on the a(w) of the treatment
      medium. The survival curves for a(w)=0.99 appeared to be linear, for a(w)=0.96
      were slightly upwardly concaved and for a(w)=0.93 and 0.90 were markedly concave
      upward. A mathematical model based on the Weibull distribution provided a good
      fit for all the survival curves obtained in this investigation. The effect of the
      temperature and a(w) on the Weibull model parameters was also studied. The shape
      parameter (p) depended on the a(w) of the treatment medium but in each medium of
      different a(w) the temperature did not have a significant effect on this
      parameter. The p parameter followed a linear relationship with a(w). The scale
      parameter (delta) decreased with the temperature following an exponential
      relationship and increased by decreasing the a(w) in the range from 0.99 to 0.93.
      However the delta parameter of survival curves obtained at a(w)=0.90 were lower
      than those obtained at a(w)=0.93. A mathematical model based on the Weibull
      parameters was built to describe the joint effect of temperature and a(w) on
      thermal inactivation of L. monocytogenes. This model provides a more complete
      information on the influence of the a(w) on the L. monocytogenes than the data
      initially generated. The model developed indicated that the effect of the a(w) on
      the thermal resistance of L. monocytogenes varied depending upon the temperature
      of treatment.

PMID- 17189764
TI  - Assessing biofilm formation by Listeria monocytogenes strains.
AB  - When a microtitre plate assay was used to quantify biofilm production by Listeria
      monocytogenes strains following growth in Tryptone Soy Broth (TSB) for 48 h at 20
      degrees C, 127 of 138 strains (92.0%) were classified as weak, 9 of 138 strains
      (6.5%) as moderate and only 2 of 138 strains (1.5%) as strong biofilm formers.
      The strains included environmental, animal, food (persistent and sporadic
      strains) and clinical isolates previously typed using esterase electrophoresis
      (ESE) and multi-locus enzyme electrophoresis (MEE). Strains from different
      sources produced similar quantities of biofilm, whereas biofilm production by ESE
      type II strains, irrespective of source, was greater than that observed for other
      ESE types. No correlation between MEE type and biofilm production was observed. A
      Petri dish assay which allowed parallel quantification and microscopic
      examination of biofilms was used to examine biofilm formation by selected L.
      monocytogenes strains during growth in TSB for 14 days at 20 degrees C. Results
      from these assays showed that following prolonged incubation, some L.
      monocytogenes strains categorized as weak biofilm formers by the 48 h microtitre
      assay, were able to form biofilms similar in terms of quantity and structure to
      those produced by strains classified as strong or medium biofilm formers. Results
      from 14-day Petri dish assays confirmed 48 h microtitre assays regarding greater
      biofilm production by ESE type II strains compared to other ESE types of L.
      monocytogenes. Biofilm production was similar for ESE type II persistent and
      sporadic food isolates but reduced for ESE type II clinical strains.

PMID- 17189765
TI  - Rhizopus oligosporus and yeast co-cultivation during barley tempeh fermentation-
      nutritional impact and real-time PCR quantification of fungal growth dynamics.
AB  - Barley tempeh was produced by fermenting barley kernels with Rhizopus
      oligosporus. The potential of the yeasts Saccharomyces cerevisiae (three
      strains), S. boulardii (one strain), Pichia anomala (one strain) and
      Kluyveromyces lactis (one strain) to grow together with R. oligosporus during
      barley tempeh fermentation was evaluated. All yeast strains grew during the
      fermentation and even during cold storage of tempeh (P<0.01). The growth of
      yeasts slightly increased the ergosterol contents, but did not influence amino
      acid contents and compositions, and did not reduce phytate contents. Slight
      increases of vitamins B(6) and niacinamide, and slight decreases of B(1) and
      biotin were observed. Quantification of fungal growth is difficult during mixed
      species fermentations because ergosterol is found in all fungal species, and
      colony-forming-unit (cfu) estimations are not reliable for R. oligosporus and
      other sporulating fungi. Therefore, we developed a quantitative real-time PCR
      method for individually quantifying S. cerevisiae and R. oligosporus growth in
      barley tempeh. The PCR results were highly correlated with the ergosterol content
      of R. oligosporus and with the number of cfu of S. cerevisiae. Thus, real-time
      PCR is a rapid and selective method to quantify yeasts and R. oligosporus during
      mixed species fermentation of inhomogenous substrate such as barley tempeh.

PMID- 17189766
TI  - Diversity of Saccharomyces strains on grapes and winery surfaces: analysis of
      their contribution to fermentative flora of Malbec wine from Mendoza (Argentina)
      during two consecutive years.
AB  - Spontaneous fermentations are still conducted by several wineries in different
      regions of Argentina as a common practice. Native Saccharomyces strains
      associated with winery equipment, grape and spontaneous fermentations of Malbec
      musts from "Zona Alta del Rio Mendoza" region (Argentina) were investigated
      during 2001 and 2002 in the same cellar. Low occurrence of Saccharomyces on
      grapes and their limited participation during fermentation were confirmed. Strain
      sequential substitution during fermentation was observed. Between 30% and 60% of
      yeast population at the end of fermentation was coming from yeasts already
      present in the winery. A stable and resident Saccharomyces micro-flora in the
      winery was confirmed. It exhibited a dynamic behaviour during season and between
      years. Commercial strains were found during fermentation in different
      percentages, but their presence on winery equipment was low. The present work
      represents a first approach to winery yeast and spontaneous fermentation
      Saccharomyces population dynamics in an important viticultural region from
      Argentina that has never been characterized before. The results obtained have an
      important significance for the local industry, showing for the first time the
      real situation of the microbial ecology of alcoholic fermentation in an
      industrial winery from Mendoza, Argentina.

PMID- 17189767
TI  - Inhibitory activity of Thai condiments on pandemic strain of Vibrio
      parahaemolyticus.
AB  - Antibacterial activity of 13 condiments used in Thai cooking was investigated
      with a pandemic strain of Vibrio parahaemolyticus. Using a disk diffusion
      technique, freshly squeezed extracts from galangal, garlic and lemon, at a
      concentration of 10 microl/disk produced a clear zone of 13.6+/-0.5, 11.6+/-0.5
      and 8.6+/-1.2mm, respectively. The inhibitory activity of these 3 condiments on
      pandemic strains was not significantly different from that on non-pandemic
      strains of V. parahaemolyticus. Because of its popularity in seafood cooking,
      galangal was subjected to further investigation. Only a chloroform extract of
      galangal inhibited growth of V. parahaemolyticus producing a clear zone of 9.5+/
      0.5, 12.0+/-0 and 13.5+/-0.5mm diameter at concentrations of 25, 50 and 100
      microg/disk, respectively. One active component is identified as 1'
      acetoxychavicol acetate. The activity of galangal was not reduced at pH 3 or in
      the presence of 0.15% bile salt but was reduced by freeze and spray drying.
      Heating a fresh preparation of galangal to 100 degrees C but not 50 degrees C for
      30 min also reduced growth inhibition. Therefore, using fresh galangal in cooking
      was recommended. The MIC and MBC of a freshly squeezed preparation of galangal
      were 1:16 and 1:16, respectively. This is the first report of an inhibitory
      activity of a Thai medicinal plant, galangal that is used in Thai cooking, on the
      pandemic strain of V. parahaemolyticus.

PMID- 17189768
TI  - Effect of temperature on the spoilage rate of whole, unprocessed crabs: Carcinus
      maenas, Necora puber and Cancer pagurus.
AB  - Shelf life of whole, initially live, crabs depended primarily on the storage
      conditions and the time at which death occurred. Large differences in the time
      that individual crab species survived particular storage conditions resulted in
      wide variations in shelf-life. Bacterial spoilage of Carcinus maenas, Necora
      puber and Cancer pagurus, measured using aerobic plate counts, indicated that on
      ice at 4 degrees C whole unprocessed crabs had a shelf life approximately 9-11
      days, at 4 degrees C approximately 13-29 days, in simulated supermarket
      conditions of sale approximately 5-7 days and at 20 degrees C approximately 2-16
      days. Storage of whole unprocessed crabs chilled at 4 degrees C considerably
      extended shelf life compared to crabs stored on ice. Live crabs stored on ice
      died within 24h, most likely due to thermal shock and their early death was
      responsible for their more rapid increase in bacterial numbers compared to crabs
      stored at 4 degrees C. No growth of bacteria occurred in the flesh of live crabs
      stored at 4 degrees C for between 128 and 504 h. Crab flesh quality deteriorated
      prior to maximum shelf-life (defined as the time at which bacterial load reached
      log 5 cfu/g crabmeat) in some instances. The best compromise between high
      crabmeat yield and long shelf-life is likely to be to transport crabs at 4
      degrees C live to market where they could be stored live at 4 degrees C without
      spoilage for 2 weeks before placed on ice at 4 degrees C, with a potential
      maximum shelf life of approximately 24 days.

PMID- 17189769
TI  - Effectiveness of domestic antibacterial products in decontaminating food contact
      surfaces.
AB  - Four commercially available antibacterial products (two wipes and two sprays)
      were tested under laboratory conditions on a range of food contact surfaces
      (wood, glass, plastic, Microban incorporated plastic). The products'
      effectiveness at preventing cross-contamination of Escherichia coli and
      Staphylococcus aureus and the influence of surface type and drying time were
      assessed. Survival of the bacterial culture (approximately 400 colonies per 8
      cm(2)) on the above preparation surfaces was determined using an in situ
      nitroblue tetrazolium (NBT) method. In the absence of any antibacterial products,
      both bacteria survived up to 120 min on all test surfaces with glass and plastic
      showing no reduction in bacterial number. The order of survival is:
      glass>plastic>>Microban incorporated plastic>wood (<8%). The length of drying
      time did not affect the survival of either bacterium on glass and plastic
      surfaces. On wood and Microban incorporated plastic, E. coli appeared to be more
      sensitive to drying time than S. aureus. Only plastic appeared to affect the
      effectiveness of the antibacterial products, where the reduction in bacterial
      number was significantly lower than the other test surfaces (p<0.05). The overall
      results suggest the antibacterial products are effective in disinfecting food
      preparing surfaces, provided products instructions are carefully followed.

PMID- 17189772
TI  - Errata in printed Hoffer Q formula.

PMID- 17189774
TI  - Scleral fixation.

PMID- 17189775
TI  - Modified technique for management of LIDRS.

PMID- 17189776
TI  - Functions of the capsular tension ring.

PMID- 17189777
TI  - Locating the nucleus after posterior capsule rupture.

PMID- 17189779
TI  - Consultation section. Refractive surgical problem.

PMID- 17189778
TI  - Multiple approaches to PCO prevention.

PMID- 17189786
TI  - Preoperative simulation of postoperative iris-fixated phakic intraocular lens
      position and simulation of aging using high-resolution Scheimpflug imaging.
AB  - To increase postoperative safety after implantation of iris-fixated phakic
      intraocular lenses (pIOLs), optimal preoperative evaluation and patient selection
      is mandatory. We present a new software tool in a high-resolution Scheimpflug
      imaging device that precisely simulates the postoperative position of an iris
      fixated pIOL and also simulates the effect of aging on the pIOL's position.

PMID- 17189787
TI  - Injection of an intraocular lens in an eye without capsular support.
AB  - We describe a technique that can be used to facilitate posterior chamber
      intraocular lens (IOL) placement with iris fixation in cases with compromised
      capsular support. This procedure allows injection of an IOL through an unenlarged
      clear corneal incision. A safety net suture is temporarily fixed in the posterior
      chamber to act as a surrogate capsule. This suture supports the IOL while the
      surgeon injects it and secures it to the iris. The addition of this single step
      facilitates the remainder of the procedure and potentially makes it safer.

PMID- 17189788
TI  - Double-clip technique in cataract surgery using topical anesthesia.
AB  - We describe a simple technique that reduces the effect of blepharospasm in the
      presence of sub-Tenon's or topical anesthesia without the administration of a lid
      block or a reduction in adequate analgesia.

PMID- 17189789
TI  - Determining corneal power using Orbscan II videokeratography for intraocular lens
      calculation after excimer laser surgery for myopia.
AB  - PURPOSE: To assess the accuracy of Orbscan II slit-scanning videokeratography for
      intraocular lens (IOL) calculation in eyes with previous photorefractive surgery
      for myopia. SETTING: Private practice, St. Louis, Missouri, USA. METHODS: Corneal
      power (K) was measured by manual keratometry, Placido-based videokeratography
      (Atlas), slit-scanning videokeratography (Orbscan II), and contact lens
      overrefraction in 21 post-photoablation eyes having cataract surgery.
      Postoperative data collected after phacoemulsification were used to back
      calculate corneal power (BCK). The BCK values were statistically compared at 3.0
      to 6.0 mm central Orbscan II curvature and power measurements, including total
      axial power, total tangential power, total mean power, and total optical power.
      Similar comparisons were made to Atlas curvature at the 0.0 to 10.0 mm zones.
      RESULTS: The mean corneal power after refractive surgery based on BCK values
      using the Holladay 2 formula (BCK H2) was 39.35 diopters (D) +/- 2.58 (SD). The
      mean manual value (40.52 +/- 1.95 D) and Atlas-based values were statistically
      higher than BCK H2 values (P<.001). The mean corneal power calculated from
      historical data was 39.33 +/- 2.70 D (P = .83 to BCK H2; n = 19) and from contact
      lens overrefraction, 41.38 +/- 3.11 D (P = .19; n = 5). Orbscan II parameters (n
      = 21) of the total mean power (3.0 mm, 39.10 +/- 2.63 D), total tangential power
      (3.0 mm, 39.11 +/- 2.60), total axial power (5.0 mm, 39.19 +/- 2.55 D), and total
      optical power (3.0 mm, 39.08 +/- 2.78 D; 4.0 mm, 39.39 +/- 2.76 D) were
      statistically similar to both the historical and BCK H2 values (P>.11). If used
      prospectively, 80.9% of eyes would have been within +/-0.50 D of the targeted
      refraction using a 4.0 mm total optical power, 76.2% using a 5.0 mm total axial
      power, and 42.1% using the historical method. CONCLUSION: The Orbscan II 5.0 mm
      total axial power and 4.0 mm total optical power can be used to more accurately
      predict true corneal power than the history-based method and may be particularly
      useful when pre-LASIK data are unavailable.

PMID- 17189790
TI  - No-history method of intraocular lens power calculation for cataract surgery
      after myopic laser in situ keratomileusis.
AB  - PURPOSE: To prospectively evaluate the no-history method for intraocular lens
      (IOL) power calculation in 15 cataractous eyes that had previous myopic laser in
      situ keratomileusis (LASIK) and for which the pre-LASIK K-readings were not
      available. SETTING: Private practice, Lynwood, California, USA. METHODS: The
      predicted IOL power was calculated in each case. Also calculated were the mean
      arithmetic and absolute IOL predictor errors, range of the prediction errors, and
      number of eyes in which the error was within +/-1.00 diopter (D). RESULTS: The
      mean arithmetic IOL prediction error was -0.003 D +/- 0.63 (SD), and the mean
      absolute IOL prediction error was 0.55 +/- 0.31 D (range -0.89 to +1.05 D).
      Fourteen eyes (93.3%) were within +/-1.00 D. The results of the Shammas post
      LASIK formula compared favorably to the results obtained with the optimized
      Holladay 1 (P = .42), Hoffer Q (P = .25), Haigis (P = .30), and Holladay 2 (P =
      .19) formulas and were better than the results obtained with the optimized SRK/T
      formula (P = .0005). CONCLUSION: The no-history method is a viable alternative
      for IOL power calculation after myopic LASIK when the refractive surgery data are
      not available.

PMID- 17189791
TI  - Synchrony dual-optic accommodating intraocular lens. Part 1: optical and
      biomechanical principles and design considerations.
AB  - PURPOSE: To describe a dual-optic accommodating intraocular lens (IOL) based on
      theoretical considerations. SETTING: University and independent research group.
      METHODS: Ray-tracing analysis using optical modeling software (ZEMAXTM, Focus
      Software Inc., Tucson, Ariz) in a theoretical model eye was used to analyze lens
      configurations to optimize the accommodative and magnification effects of axial
      lens displacement. Finite-element modelling using a commercially available PC
      based software package (COSMOS DesignSTAR) was applied to design the
      biomechanical parameters of the inter-optic articulations and optics. RESULTS:
      Ray-tracing analysis indicated that a dual-optic design with a high plus-powered
      front optic coupled to a minus posterior optic produced greater change in
      conjugation power of the eye compared to a single-optic intraocular lens and that
      magnification effects were unlikely to account for improved near vision. Finite
      element modelling indicated that the 2 optics can be linked by spring-loaded
      haptics that allow anterior and posterior axial displacement of the front optic
      in response to changes in ciliary body tone and capsular tension. CONCLUSION: A
      dual-optic design linked by spring haptics increases the accommodative effect of
      axial optic displacement with minimal magnification effect and has promise for
      improving the performance of accommodative intraocular lenses.

PMID- 17189792
TI  - Synchrony dual-optic accommodating intraocular lens. Part 2: pilot clinical
      evaluation.
AB  - PURPOSE: To evaluate the clinical outcomes of an accommodating dual-optic
      intraocular lens (IOL). SETTING: Private practice and university centers.
      METHODS: A prospective noncomparative case series with retrospective control
      comprised 21 patients (26 eyes) scheduled for small-incision extracapsular
      cataract extraction by phacoemulsification with implantation of the Synchrony
      dual-optic accommodating IOL (Visiogen) (accommodating IOL group) and 10 patients
      who had small-incision extracapsular phacoemulsification with implantation of a
      monofocal, single-optic IOL at least 6 months previously (control group).
      Patients were examined 1, 3, 6, and 12 months after surgery. Defocus curves in
      the accommodating IOL group were compared with those in the control group. The
      main outcome measures were postoperative distance uncorrected and best corrected
      visual acuity; near uncorrected, distance corrected, and near corrected visual
      acuity; and accommodative range based on defocus curves. RESULTS: Twenty-four
      eyes were available at the 6-month follow-up visit. All eyes had best corrected
      distance visual acuity of 20/40 or better, and 19 eyes (79%) had an uncorrected
      distance visual acuity of 20/40 or better. Uncorrected near visual acuity was
      20/40 or better in all eyes. With distance correction, 23 eyes (96%) had an
      acuity of 20/40 or better at near. Defocus curve analysis suggested a mean
      accommodative range of 3.22 diopters (D) +/- 0.88 (SD) (range 1.00 to 5.00 D) in
      the accommodating IOL group and 1.65 +/- 0.58 D in the control group (range 1.00
      to 2.50 D) (P<.05). CONCLUSION: The Synchrony dual-optic IOL shows promise as an
      option to provide accommodative function in pseudophakic patients.

PMID- 17189793
TI  - Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular
      inflammation associated with cataract surgery.
AB  - PURPOSE: To determine whether nepafenac ophthalmic suspension 0.1% decreases the
      incidence and severity of inflammation and pain after cataract surgery with
      posterior chamber intraocular lens implantation. SETTING: Twenty-one
      ophthalmology clinics in the United States. METHODS: A randomized double-blind
      vehicle-controlled trial was conducted in which adult patients were randomly
      assigned to receive nepafenac 0.1% or vehicle beginning 1 day before surgery and
      continuing on the day of surgery (day 0) for 14 days. Patients were evaluated on
      days 1, 3, 7, and 14. The primary efficacy variable was the percentage of
      patients cured at day 14 (cure defined as aqueous cells score + aqueous flare
      score = 0). Other efficacy variables included percentage of patients who were
      pain free at all visits and aqueous cells, flare, and cells plus flare scores.
      RESULTS: The mean age of the 476 patients (243 nepafenac, 233 vehicle) was 70
      years (range 27 to 93 years). At day 14, 152 patients (62.6%) in the nepafenac
      group and 40 (17.2%) in the vehicle group were cured (P<.0001). A higher
      percentage of patients in the nepafenac group was pain free at all visits
      (P<.0001). Throughout the study, most nepafenac-treated patients were pain free
      (83.1% to 93.0%) compared with less than half the vehicle-treated patients (41.6%
      to 46.4%). The nepafenac group had lower mean aqueous cells, flare, and cells
      plus flare scores at all visits (P<.0001). No treatment-related ocular adverse
      events occurred in either group. CONCLUSION: Nepafenac ophthalmic suspension 0.1%
      was safe and effective for preventing and treating ocular inflammation and pain
      associated with cataract surgery.

PMID- 17189794
TI  - Aqueous humor penetration of gatifloxacin and moxifloxacin eyedrops given by
      different methods before cataract surgery.
AB  - PURPOSE: To determine whether the penetration into the aqueous humor of 2 new
      fourth-generation fluoroquinolone antibiotics, gatifloxacin (Zymar) and
      moxifloxacin (Vigamox) eyedrops, was affected by different methods of
      administration before cataract surgery. SETTING: Pasqua Hospital, Regina,
      Saskatchewan, Canada. METHODS: This prospective randomized study comprised 193
      patients. The patients were divided into 2 main groups. One group received
      gatifloxacin eyedrops and the other, moxifloxacin eyedrops. Each group was
      subdivided into 4 subgroups. All patients received the drops 4 times a day
      starting 2 days preoperatively. The first subgroup did not receive any more
      antibiotics. The second subgroup received the antibiotic drops 3 times, starting
      approximately 2 hours preoperatively. The third subgroup received a wick soaked
      in a dilating mixture containing the antibiotic. The fourth subgroup received the
      wick and the antibiotic drops at the time of preparation for surgery. At the
      beginning of surgery, 0.1 mL of aqueous humor was aspirated, frozen, and sent
      under ice by courier to the Provincial Laboratory for analysis by high
      performance liquid chromatography. RESULTS: The study included 124 women and 69
      men. The mean concentrations in the aqueous humor were 0.19, 0.82, 0.22, and 0.30
      microg/mL in the 4 gatifloxacin subgroups, respectively, and 0.38, 2.16, 0.88,
      and 0.97 microg/mL in the 4 moxifloxacin subgroups, respectively. Analysis of
      variance showed the differences between the 2 antibiotics to be statistically
      significant. CONCLUSIONS: Moxifloxacin penetrated the aqueous humor better than
      gatifloxacin regardless of the method of administration. Both antibiotics
      penetrated the aqueous humor well when given in drop form. They reached and
      exceeded the minimum inhibitory concentration levels for the most common ocular
      pathogens causing endophthalmitis. Only moxifloxacin reached these levels when
      the wick was used.

PMID- 17189795
TI  - Safety of prophylactic intracameral moxifloxacin 0.5% ophthalmic solution in
      cataract surgery patients.
AB  - PURPOSE: To determine the safety of prophylactic intracameral moxifloxacin 0.5%
      ophthalmic solution (Vigamox) in patients having cataract surgery. SETTING:
      American Eye Center, Manila, Philippines. METHODS: Preoperative and 1-month
      postoperative anterior chamber reaction, corneal endothelial cell density, and
      corneal thickness were assessed in 65 eyes that had cataract surgery with
      intracameral moxifloxacin. All eyes received 0.1 mL intracameral moxifloxacin
      0.5% ophthalmic solution containing 500 mug of moxifloxacin as the last step of
      phacoemulsification. Different ophthalmologists conducted the postoperative
      evaluation in an observer-masked fashion. A P value less than 0.05 was considered
      significant. RESULTS: All 65 eyes completed the study. The mean age was 69.5
      years +/- 9.13 (SD) (range 48 to 84 years). All eyes had a postoperative best
      corrected visual acuity of 20/30 or better. All eyes had trace to +2 cells and
      flare anterior chamber reaction only on the first day after surgery. The mean
      endothelial cell count was 2491.52 cells/mm(2) preoperatively and 2421.58
      cells/mm(2) postoperatively. The mean difference was 70 cells/mm(2), which not
      statistically significant (P = .737). The increase of 17.80 microm in
      postoperative pachymetry 1 month after surgery was not statistically significant
      (P>.65). CONCLUSION: Intracameral Vigamox 0.5 mg/mL appeared to be nontoxic in
      terms of visual rehabilitation, anterior chamber reaction, pachymetry, and
      corneal endothelial cell density.

PMID- 17189796
TI  - Intacs for the correction of keratoconus: two-year follow-up.
AB  - PURPOSE: To evaluate the long-term safety and efficacy of Intacs segments
      (Addition Technology, Inc.) for the treatment of keratoconus in terms of
      intraoperative and postoperative complications, visual outcome, restoration of
      contact lens tolerance, and inhibition of disease progression. SETTING: Service
      d'Ophtalmologie, CHU Pellegrin, Bordeaux, France. METHODS: This prospective, 2
      year follow-up study comprised 100 keratoconic eyes with clear central corneas
      and contact lens intolerance. The best spectacle-corrected visual acuity (BSCVA),
      uncorrected visual acuity (UCVA), refractive error, keratometry, pachymetry, and
      slitlamp examination were assessed preoperatively and 1 and 2 years after Intacs
      implantation. RESULTS: At 2 years, the UCVA and BCVA improved in 80.5% and 68.3%
      of eyes, respectively (P<.001). The proportion of eyes with a BCVA >or=0.5
      (20/40) increased from 22.0% at baseline to 51.2% and 53.7% at 1 year and 2
      years, respectively (P<.001). The manifest refraction spherical equivalent
      improved from a mean of -6.93 diopters (D) +/- 3.91 (SD) preoperatively to -4.01
      +/- 3.16 D at 1 year and -3.80 +/- 2.73 D at 2 years (P<.001). The mean
      keratometry readings decreased from 50.1 +/- 5.6 D preoperatively to 46.4 +/- 5.3
      D at 1 year and 46.8 +/- 4.9 D at 2 years (P<.001). Contact lens tolerance was
      restored in over 80% of cases. Postoperative slitlamp observations revealed no
      clinically significant issues. The segments were removed from 4 eyes without
      complications or sequelae. CONCLUSION: Intacs implantation was a safe and
      efficacious treatment for keratoconus. Significant and sustained improvements in
      objective visual outcomes were achieved in most cases, with restoration of
      contact lens tolerance.

PMID- 17189798
TI  - Three-hundred-sixty degree barrier effect of a square-edged and an enhanced-edge
      intraocular lens on centripetal lens epithelial cell migration Two-year results.
AB  - PURPOSE: To study the 360-degree barrier effect of an intraocular lens (IOL) with
      a square edge at the optic and an enhanced square edge at the optic-haptic
      junctions (Rayner 570C C-flex) on centripetal migration of lens epithelial cells
      (LECs) over a 2-year period. SETTING: Department of Ophthalmology, Scarborough
      Hospital, Scarborough, United Kingdom. METHODS: In a prospective study of 40
      consecutive eyes, a C-flex IOL was implanted in the bag after phacoemulsification
      surgery. Eyes with intraoperative complications, requiring additional procedures,
      without 360-degree overlap of the optic, or with capsule block syndrome were
      excluded. Follow-up was at 6, 10, 18, and 24 months. At each visit, high
      magnification retroillumination digital photographs were taken using a slitlamp
      attached digital camera. The barrier effect to LEC migration across the optic
      edge and the enhanced square edge at the optic-haptic junction was graded as
      complete (no epithelial pearls or sheet), partial (few epithelial pearls without
      sheet), and minimal/none (epithelial sheet behind the IOL optic). RESULTS: Twenty
      four patients came to the final follow-up at 24 months. Fifteen of these eyes
      (63%) had a complete barrier effect throughout the 360 degrees of the IOL. Three
      eyes (13%) had a partial barrier effect throughout the 360 degrees of the IOL.
      Three eyes had a complete optic barrier effect but a partial optic-haptic
      junction barrier effect. Three eyes had a partial optic barrier effect but a
      complete optic-haptic junction barrier effect. No eye had epithelial sheets
      extending behind the optic at any location. CONCLUSIONS: This study showed the
      barrier effect of the edge design of the C-flex IOL and the efficacy of the
      enhanced edge in preventing LEC migration at the optic-haptic junction. The
      enhanced edge was as effective as a sharp square edge in restricting the LEC
      migration.

PMID- 17189797
TI  - Effect of inferior-segment Intacs with and without C3-R on keratoconus.
AB  - PURPOSE: To determine whether corneal collagen cross-linking with riboflavin (C3
      R) augments the effect of inferior-segment Intacs (Addition Technology) in the
      treatment of keratoconus. SETTING: Private practice, Beverly Hills, California,
      USA. METHODS: A retrospective nonrandomized comparative case series comprised 12
      eyes of 9 patients who had inferior-segment Intacs placement without C3-R (Intacs
      only group) and 13 eyes of 12 patients who had inferior-segment Intacs placement
      combined with C3-R (Intacs with C3-R group). The 2 groups were matched
      preoperatively. All patients had inferior-segment Intacs placed with the incision
      in the steep axis of manifest refraction. Corneal collagen cross-linking with
      riboflavin was performed after the Intacs segments were inserted. Outcome
      measures were topographic keratometry values and the lower-upper (L-U) ratio,
      which is a topographic measure of the degree of keratoconus. Preoperative data
      were compared to results 1 day postoperatively and measurements at the last
      postoperative visit. RESULTS: The Intacs with C3-R group had a significantly
      greater reduction in cylinder than the Intacs-only group (P<.05). Steep and
      average keratometry were reduced significantly more in the Intacs with C3-R group
      (P<.05). There was a greater reduction in L-U ratio in the Intacs with C3-R group
      (P<.05). CONCLUSION: The addition of C3-R to the Intacs procedure resulted in
      greater keratoconus improvements than Intacs insertion alone.

PMID- 17189799
TI  - Comparison of pseudophakic dysphotopsia with Akreos Adapt and SN60-AT intraocular
      lenses.
AB  - PURPOSE: To determine the relative incidence of unwanted light images with the
      AcrySof SN60-AT intraocular lens (IOL) (Alcon) and the Akreos Adapt (Bausch &
      Lomb) IOL. SETTING: The Eye Clinic, Sir Charles Gairdner Hospital, Nedlands,
      Australia. METHODS: In a prospective randomized study of 61 patients who had
      cataract surgery, the relative incidence of unwanted light images with 2 biconvex
      acrylic double square-edged IOLs, the SN60-AT and Akreos Adapt, was compared.
      Patients were followed at 1 week and for a minimum of 6 weeks. At both follow
      ups, patients were asked to rate their experience of dysphotopic phenomenon
      according to a set of questionnaire criteria. The Mann-Whitney test was used to
      analyze the ordinal data. RESULTS: All 61 patients were interviewed at both
      stages of follow-up. The mean follow-up was 8 weeks +/- 2 (SD). At 1 week, there
      was significantly more dysphotopsia (positive and negative) with the SN60-AT IOL
      (37.5%) than with the Akreos Adapt IOL (24.1%) (P = .042). Significantly more
      patients with the SN60-AT IOL reported negative dysphotopsia at 1 week only. At 8
      weeks, the incidence of positive and negative dysphotopsia declined to 31.3% and
      20.7% in the SN60-AT group and Akreos Adapt group, respectively, and there was no
      longer a statistically significant difference between the 2 groups. CONCLUSIONS:
      More patients with the SN60-AT IOL than with the Akreos Adapt IOL reported
      dysphotopsia. One week postoperatively, the difference was significant. The
      difference was primarily a result of the higher incidence of negative
      dysphotopsia with the SN60-AT IOL. At 8 weeks, the incidence of all types of
      light phenomena was significantly lower in both groups.

PMID- 17189800
TI  - Profile of clear corneal cataract incisions demonstrated by ocular coherence
      tomography.
AB  - PURPOSE: To examine the profile of clear corneal cataract incisions in the living
      eye using optical coherence tomography (OCT). SETTING: Private practice, Eugene,
      Oregon, USA. METHODS: The Zeiss Visante OCT anterior segment imaging system was
      used to study the profile of clear corneal cataract incisions, all in senior
      citizens. The OCT images of the operative eye were taken on the first
      postoperative day approximately 24 hours after surgery. The OCT images of clear
      corneal incisions were compared with an OCT image of a control eye, incisions
      without stromal hydration, and previous drawings of clear corneal incisions.
      RESULTS: In the images, the clear corneal incisions had an arcuate configuration
      rather than a straight line configuration, as previously indicated. This
      architecture appears to add greater stability as a result of a tongue-and-groove
      like fit of the floor to the roof of the incision as well as an incision that is
      longer than the chord length that had previously been measured. Other findings
      include that stromal swelling, which facilitates sealing of these incisions by
      the endothelial pump, lasted for at least 24 hours. CONCLUSIONS: Results indicate
      an incision in the plane of the cornea with a chord length of at least 2.0 mm
      provides advantageous architecture for adequate self-sealing. Proper clear
      corneal incision construction resulted in an incision architecture that seemed to
      have increased stability and added safety, contributing to an absence of
      endophthalmitis for more than 10 years and 9000 cases in a single practice.

PMID- 17189801
TI  - Tetracaine hydrochloride 0.5% versus lidocaine 2% jelly as a topical anesthetic
      agent in cataract surgery: comparative clinical trial.
AB  - PURPOSE: To assess the anesthetic efficacy of tetracaine hydrochloride 0.5%
      (TetraVisc) versus lidocaine 2% jelly in routine cataract extraction. SETTING:
      Private surgicenter, Warwick, Rhode Island, USA. METHODS: A prospective
      randomized double-blind clinical trial comprised 100 patients having routine
      cataract extraction by clear corneal phacoemulsification. Patients were
      randomized to receive TetraVisc or lidocaine 2% jelly, applied once,
      approximately 5 minutes before surgery. Outcomes included a self-reported
      postoperative pain score and the need for supplemental anesthesia. RESULTS: The
      mean self-reported postoperative pain scores for TetraVisc and lidocaine 2% jelly
      were similar (0.94 and 1.02, respectively; P = .76). A single patient in the
      lidocaine group required supplemental anesthesia. CONCLUSION: TetraVisc was as
      effective as lidocaine 2% jelly as a topical anesthetic agent for routine
      cataract extraction.

PMID- 17189802
TI  - Pupil dilation with intracameral lidocaine during phacoemulsification.
AB  - PURPOSE: To evaluate pupil dilation by an intracameral injection of nonpreserved
      lidocaine 1% during phacoemulsification cataract extraction and compare the
      results with those using conventional topical mydriatics. SETTING: Department of
      Ophthalmology, Rassoul Akram Hospital, Iran University of Medical Sciences,
      Tehran, Iran. METHODS: A prospective comparative case series study was conducted.
      The study included 57 patients who were given topical mydriatics (30 eyes) or
      intracameral lidocaine (27 eyes) to dilate the pupil for phacoemulsification and
      intraocular lens implantation. The topical group received 3 drops of
      cyclopentolate 1% and phenylephrine 5% given 5 minutes apart starting 60 minutes
      before surgery. The intracameral group received preservative-free lidocaine 1%
      (0.2 to 0.3 mL) injected just before the procedure began. No epinephrine was
      added to the irrigating solution. In both groups, the horizontal pupil diameter
      was measured before and after pupil dilation using the same caliper. Total
      surgical time, need for a mydriatic agent during the procedure, and subjective
      surgical performance were recorded. RESULTS: The mean age, sex, cataract density,
      baseline horizontal pupil diameter, and mean duration of the surgery were the
      same between the topical group and intracameral group. The mean pupil dilation
      was 4.52 mm +/- 0.08 (SD) in the intracameral group and 4.06 +/- 0.09 mm in the
      topical group; the difference between groups was statistically significant (P =
      .001). There was no significant difference between groups in the overall
      subjective surgical performance (P = .74). No patient in the intracameral group
      and 2 patients in the topical group required an intracameral mydriatic injection.
      CONCLUSION: During phacoemulsification, intracameral preservative-free lidocaine
      1% provided rapid, effective mydriasis comparable that of topical mydriatics.

PMID- 17189803
TI  - Posterior capsule opacification after combined cataract surgery and vitrectomy.
AB  - PURPOSE: To compare the degree of posterior capsule opacification (PCO) after
      combined cataract surgery and vitrectomy and after cataract surgery alone in age
      matched control patients and in patients with and without diabetes mellitus (DM).
      SETTING: Sugita Eye Hospital, Nagoya, Japan. METHOD: In a prospective study,
      patients were divided into 2 groups: those having cataract surgery alone
      (cataract group) and those having combined cataract and vitrectomy surgery
      (combined group). The 2 groups were further divided into patients without DM (non
      DM subgroup) and patients with DM (DM subgroup). The PCO rates were determined 3,
      6, and 12 months after surgery using the POCO system. RESULTS: In the cataract
      group, the non-DM subgroup and the DM subgroup each comprised 42 eyes of 42
      patients. In the combined group, the non-DM subgroup comprised 26 eyes of 26
      patients and the DM subgroup, 23 eyes of 23 patients. In the cataract group, the
      PCO rate in the DM subgroup was significantly higher than in the non-DM subgroup
      at every postoperative examination (P<.05). In the non-DM subgroup, the PCO rate
      was significantly higher at every postoperative examination in patients having
      combined surgery than in patients having cataract surgery alone (P<.05). In the
      combined group, the PCO rate did not differ significantly between the non-DM
      subgroup and the DM subgroup. CONCLUSION: Even patients without DM must be
      carefully monitored for PCO development after combined surgery.

PMID- 17189805
TI  - Operator-induced errors in Hartmann-Shack wavefront sensing: model eye study.
AB  - PURPOSE: To evaluate the effects of instrument realignment and angular
      misalignment during the clinical determination of wavefront aberrations by
      simulation in model eyes. SETTING: Aston Academy of Life Sciences, Aston
      University, Birmingham, United Kingdom. METHODS: Six model eyes were examined
      with wavefront-aberration-supported cornea ablation (WASCA) (Carl Zeiss Meditec)
      in 4 sessions of 10 measurements each: sessions 1 and 2, consecutive repeated
      measures without realignment; session 3, realignment of the instrument between
      readings; session 4, measurements without realignment but with the model eye
      shifted 6 degrees angularly. Intersession repeatability and the effects of
      realignment and misalignment were obtained by comparing the measurements in the
      various sessions for coma, spherical aberration, and higher-order aberrations
      (HOAs). RESULTS: The mean differences between the 2 sessions without realignment
      of the instrument were 0.020 microm +/- 0.076 (SD) for Z(3)(-1)(P = .551), 0.009
      +/- 0.139 microm for Z(3)(1)(P = .877), 0.004 +/- 0.037 microm for Z(4)(0) (P =
      .820), and 0.005 +/- 0.01 microm for HO root mean square (RMS) (P = .301).
      Differences between the nonrealigned and realigned instruments were -0.017 +/-
      0.026 microm for Z(3)(-1)(P = .159), 0.009 +/- 0.028 microm for Z(3)(1) (P =
      .475), 0.007 +/- 0.014 microm for Z(4)(0)(P = .296), and 0.002 +/- 0.007 microm
      for HO RMS (P = 0.529; differences between centered and misaligned instruments
      were -0.355 +/- 0.149 microm for Z(3)(-1) (P = .002), 0.007 +/- 0.034 microm for
      Z(3)(1)(P = .620), -0.005 +/- 0.081 microm for Z(4)(0)(P = .885), and 0.012 +/-
      0.020 microm for HO RMS (P = .195). Realignment increased the standard deviation
      by a factor of 3 compared with the first session without realignment.
      CONCLUSIONS: Repeatability of the WASCA was excellent in all situations tested.
      Realignment substantially increased the variance of the measurements. Angular
      misalignment can result in significant errors, particularly in the determination
      of coma. These findings are important when assessing highly aberrated eyes during
      follow-up or before surgery.

PMID- 17189804
TI  - Factors influencing refractive outcomes after combined phacoemulsification and
      pars plana vitrectomy: results of a prospective study.
AB  - PURPOSE: To evaluate the factors influencing the refractive outcomes of combined
      phacoemulsification, foldable intraocular lens (IOL) implantation, and pars plana
      vitrectomy (PPV). SETTING: Department of Ophthalmology, Seoul National University
      Hospital, Seoul, Korea. METHODS: One hundred fifty-four consecutive patients who
      had combined phacoemulsification, IOL implantation, and PPV between September
      2001 and August 2004 were enrolled in a prospective study. Refractive,
      keratometric, and axial length measurements were performed preoperatively and 4
      months postoperatively. The factors influencing the postoperative refractive
      outcomes were analyzed. RESULTS: The mean refractive prediction error (ie, actual
      minus predicted spherical equivalent [SE]) was -0.06 diopters (D) +/- 0.75 (SD).
      In long eyes (preoperative axial length more than 24.5 mm), the mean predicted SE
      and actual SE were -0.81 +/- 0.76 D and -1.24 +/- 0.79 D, respectively; the
      difference was significantly different (P = .001, paired t test). Patients with a
      preoperative visual acuity worse than 5/200 and those with preoperative foveal
      detachment had a significant postoperative myopic shift (P = 0.024 and P = 0.002,
      respectively; paired t test). Postoperative refractive error was not influenced
      by the intraocular air or gas tamponade during surgery (P = 0.336, paired t
      test). CONCLUSIONS: The combined surgery included a small biometric error that
      was within the tolerable range in most cases. However, myopic shifts developed in
      patients with long axial lengths, poor preoperative visual acuity, and the
      preoperative presence of foveal detachment.

PMID- 17189806
TI  - Effect of ophthalmic solution components on acrylic intraocular lenses.
AB  - PURPOSE: To investigate the effect of ophthalmic solution components on the
      surface of acrylic intraocular lenses (IOLs). SETTING: Department of
      Opthalmology, Showa University School of Medicine. METHODS: Measurement of the
      contact angles of ophthalmic solutions on 3 acrylic IOLs was performed. The
      solutions were diclofenac sodium (Diclod), bromfenac sodium (Bronuck),
      betamethasone phosphate (Rinderon), dibekacin sulfate (Panimycin), polysorbate 80
      (Tween 20), benzalkonium chloride, chlorobutanol, methylparahydroxybenzoate, and
      propylparahydroxybenzoate. The IOLs were incubated at 35 degrees C for 2 weeks in
      undiluted ophthalmic solutions and in 1:10 dilutions of ophthalmic solution
      components. The IOLs were sectioned and observed by scanning electron microscopy.
      RESULTS: The contact angle of Diclod and Bronuck solutions was the smallest. The
      contact angle of Rinderon and Panimycin was similar to that of distilled water.
      Scanning electron microscopy examination of IOLs incubated in ophthalmic solution
      components showed intralenticular changes. The IOLs immersed in ophthalmic
      solutions did not show any change, even after extended incubation. CONCLUSION:
      The chemical components of ophthalmic solutions, such as surfactants and
      solvents, permeate acrylic IOLs, suggesting the potential for long-term adverse
      effects of eyedrops in pseudophakic eyes.

PMID- 17189807
TI  - Interaction with intraocular lens materials: does heavy silicone oil act like
      silicone oil?
AB  - PURPOSE: To determine the interaction of heavy silicone oil with various
      intraocular lens (IOL) materials and whether heavy silicone oil covers the
      silicone IOL optic as silicone oil does. SETTING: Department of Ophthalmology,
      Dokuz Eylul University, Izmir, Turkey. METHODS: The study group comprised 5
      poly(methyl methacrylate) (PMMA) IOLs, 4 foldable silicone IOLs, 5 foldable
      hydrophilic acrylic IOLs, and 5 foldable hydrophobic acrylic IOLs. Each IOL was
      bathed in balanced salt solution (BSS) for 10 minutes and then placed in heavy
      silicone oil dyed with Sudan Black for another 10 minutes. Afterward, each IOL
      was reimmersed in BSS for 5 minutes and examined under the light microscope.
      Digital images were analyzed to determine the optic area covered with heavy
      silicone oil. RESULTS: The mean heavy silicone oil coverage was 7.05% +/- 7.88%
      (SD) (range 1.13% to 20.54%) on PMMA IOLs, 100% on silicone IOLs, 12.17% +/-
      11.43% (range 1.25% to 31.52%) on hydrophobic acrylic IOLs, and 34.64% +/- 13.28%
      (range 12.57% to 44.42%) on hydrophilic acrylic IOLs. Heavy silicone oil coverage
      of silicone IOLs was statistically significantly greater than the coverage of
      other IOL materials. CONCLUSION: Heavy silicone oil acted the same as silicone
      oil and covered the entire surface of silicone IOLs.

PMID- 17189808
TI  - Malignant glaucoma after phacoemulsification: treatment with diode laser
      cyclophotocoagulation.
AB  - Phacoemulsification was performed in an 84-year-old woman with ocular
      hypertension and narrow drainage angles, previously treated by neodymium:YAG
      (Nd:YAG) laser peripheral iridotomy. Despite temporal zonular weakness, the
      surgery was uneventful. An intraocular lens (IOL) was placed and centered in the
      capsular bag. Two months later, the patient presented with malignant glaucoma.
      The IOL optic was anteriorly displaced in the capsular bag, and the IOL shift
      correlated with a -4.0 diopter myopic refractive error. There was no response
      after medical treatment or Nd:YAG hyaloidotomy. One week later, a single
      treatment with transscleral diode laser cyclophotocoagulation was performed. The
      intraocular pressure normalized and the anterior chamber deepened within 48
      hours. The patient's condition has remained stable for 3 months with no further
      treatment; the Snellen visual acuity is 6/9. If medical therapy fails to control
      malignant glaucoma, cyclodiode laser treatment may be more effective and have
      fewer risks than current laser and surgical interventions.

PMID- 17189809
TI  - Excimer laser exacerbation of Avellino corneal dystrophy.
AB  - We review the clinical, histopathological, and ultrastructural findings and DNA
      phenotyping of a patient with Avellino corneal dystrophy exacerbated by laser in
      situ keratomileusis. The findings are reported and interpreted in the context of
      a literature review. The case highlights the possible difficulty of recognizing
      subtle dystrophic findings, as well as the importance of avoiding refractive
      surgical intervention in patients with Avellino corneal dystrophy to avoid
      exacerbation of dystrophic deposits in the cornea and subsequent reduction in
      vision.

PMID- 17189810
TI  - Intraocular lens opacification after nonpenetrating glaucoma surgery with
      mitomycin-C.
AB  - A 58-year-old woman had successful phacoemulsification with intraocular lens
      (IOL) implantation in January 2001. Two years later, nonpenetrating glaucoma
      surgery with mitomycin-C (MMC) 0.02% was performed for uncontrolled glaucoma. Two
      months later, opacification of the anterior IOL surface was observed. The IOL was
      removed and a hydrophobic acrylic AcrySof IOL (Alcon) implanted. The opacified
      IOL was studied by flame atomic absorption spectrometry, which showed the
      presence of calcium carbonate. A new IOL of the same model was placed in an
      aqueous solution with calcium carbonate and basic pH, and the same opacification
      developed. We hypothesize that the change in aqueous humor pH after glaucoma
      surgery and the characteristics of the IOL precipitated deposition of calcium.

PMID- 17189811
TI  - Laser in situ keratomileusis for astigmatism following laser thermal
      keratoplasty.
AB  - We describe 2 cases in which a staged laser in situ keratomileusis procedure was
      used to treat residual hyperopia and astigmatism after laser thermal
      keratoplasty. The procedure successfully reduced the spherical equivalent
      refractive error and residual astigmatism. All eyes maintained their best
      spectacle-corrected visual acuity and had an uncorrected visual acuity of at
      least 20/25 at the end of follow-up.

PMID- 17189812
TI  - Multifocal lamellar keratitis following laser in situ keratomileusis.
AB  - Over a period of approximately 7 months, multiple subepithelial spots were noted
      in one or both corneas of some patients examined 2 to 6 months after laser in
      situ keratomileusis (LASIK). The lesions appeared identical to adenovirus
      keratitis. The eyes were quiet, had good vision, and no patient had a history of
      adenoviral keratoconjunctivitis. In all eyes, the lesions resolved spontaneously
      or with topical steroid eyedrops. All investigations were negative for
      adenovirus. Corneal laser scanning in vivo confocal microscopy revealed
      Langerhans cells in the epithelium, which disappeared after the lesions resolved.

PMID- 17189814
TI  - Femtosecond-laser-assisted Descemet's stripping endothelial keratoplasty.
AB  - To our knowledge, we describe the first patient with pseudophakic bullous
      keratoplasty treated with femtosecond-laser-assisted endothelial keratoplasty. A
      5.5 mm corneoscleral tunnel incision was made; after Descemet's membrane was
      stripped, an 8.0 mm posterior lamellar corneal disk prepared with a femtosecond
      laser was inserted into the anterior chamber against the recipient cornea without
      the use of corneal sutures. Four months postoperatively, the posterior corneal
      disk was clear and the induced astigmatism was 2.1 diopters, demonstrating a
      functional corneal endothelial layer. The femtosecond laser offers a new surgical
      approach for minimally invasive endothelial keratoplasty in corneal endothelial
      disorders.

PMID- 17189813
TI  - Topography-guided vertical implantation of Intacs using a femtosecond laser for
      the treatment of keratoconus.
AB  - We report 2 cases of vertical implantation of Intacs (Addition Technology) for
      the correction of keratoconus with temporal cones. Case 1 was a 16-year-old boy.
      In the left eye, the refraction was -4.50 x 100, with an uncorrected visual
      acuity (UCVA) of 0.5 and a best corrected visual acuity (BCVA) of 0.7. The
      flattest meridian (K1) was 43.7@100 and the steepest meridian (K2), 46.9@10. Case
      2 was a 20-year-old woman. In the left eye, the refraction was -6.00 -7.00 x 100,
      with a UCVA of 0.05 and a BCVA of 0.1; K1 was 51.3@25 and K2, 55.1@115. In each
      patient, 2 Intacs segments of 0.45 mm and 0.25 mm were inserted in the temporal
      and nasal regions, respectively. One year postoperatively, the UCVA was 0.7 and
      0.3 in Case 1 and Case 2, respectively, and the BCVA was 0.8 and 0.5,
      respectively. The postoperative refraction was -2.50 x 110 in Case 1 and -5.25 x
      95 in Case 2. Based on the localization of the cone, Intacs implantation appeared
      to improve visual acuity in keratoconic patients.

PMID- 17189815
TI  - In vivo fluorescein staining of SI-30NB silicone intraocular lens.
AB  - We report a case of a 48-year-old pseudophakic woman who presented 3 weeks after
      Heidelberg retinal angiography using intravenous sodium fluorescein 2%. Bilateral
      retinal vasculitis with severe retinal ischemia and extensive capillary dropouts
      had been diagnosed. Anterior segment examination revealed green staining on the
      silicone optic of the 3-piece SI-30NB intraocular lens (IOL) (AMO), with no cell
      or flare in the aqueous humor. The anterior and posterior capsules were not
      stained. The patient did not report dark vision, double vision, or altered color
      vision. The anterior and posterior IOL surfaces demonstrated an autofluorescence
      at the time of fundus photography, which persisted to the 6-week examination
      although there were no symptoms. This is suggestive of deposits of sodium
      fluorescein on the IOL surface following angiography.

PMID- 17189816
TI  - Hyperopic shift with posterior bowing of a Collamer posterior chamber intraocular
      lens.
AB  - Two patients developed a hyperopic shift following uneventful phacoemulsification
      with implantation of a Collamer plate-haptic intraocular lens (Staar Surgical) in
      the capsular bag. Posterior bowing of the IOL was corrected by IOL exchange,
      achieving near emmetropia.

PMID- 17189817
TI  - Postmortem microscopic evaluation and clinical correlation of a pseudophakic eye
      with pseudoexfoliation and loss of zonular support.
AB  - We describe a pseudophakic patient with pseudoexfoliation who developed late
      intraocular lens (IOL) instability manifested by pseudophakodonesis, a change in
      refraction, and loss of glaucoma control. The patient subsequently required
      glaucoma surgery that was complicated by vitreous loss. Preoperative ultrasound
      biomicroscopy (UBM) failed to provide useful information regarding the zonular
      status. The patient died as a result of a malignancy, and the eye was donated for
      research. Anatomical evaluation confirmed the clinical impression of IOL
      placement in the bag and zonular laxity. Postmortem UBM helped explain some of
      the technical difficulties in examining zonules in the pseudophakic state.

PMID- 17189818
TI  - Occurrence and prognosis of nonpenetrating injuries in eyes with Verisyse iris
      supported phakic intraocular lens.
AB  - We report 8 cases of blunt trauma in patients with a Verisyse phakic intraocular
      lens (pIOL) (AMO). Two cases resulted in dislocation of the pIOL that required
      repositioning; the other 6 were managed conservatively. In all cases, the
      outcomes were satisfactory, with no further complications. The cases represent
      scenarios that patients and physicians might encounter postoperatively and
      describe ways to manage the complication.

PMID- 17189819
TI  - Intraoperative floppy-iris syndrome, alpha1-adrenergic antagonists, and chronic
      intake of mianserin: is there an association?

PMID- 17189820
TI  - Labetalol causing intraoperative floppy-iris syndrome.

PMID- 17189821
TI  - Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil
      function.
AB  - As a cornerstone of the innate immune response, neutrophils are the archetypical
      phagocytic cell; they actively seek out, ingest, and destroy pathogenic
      microorganisms. To achieve this essential role in host defense, neutrophils
      deploy a potent antimicrobial arsenal that includes oxidants, proteinases, and
      antimicrobial peptides. Importantly, oxidants produced by neutrophils, referred
      to in this article as reactive oxygen (ROS) and reactive nitrogen (RNS) species,
      have a dual function. On one hand they function as potent antimicrobial agents by
      virtue of their ability to kill microbial pathogens directly. On the other hand,
      they participate as signaling molecules that regulate diverse physiological
      signaling pathways in neutrophils. In the latter role, ROS and RNS serve as
      modulators of protein and lipid kinases and phosphatases, membrane receptors, ion
      channels, and transcription factors, including NF-kappaB. The latter regulates
      expression of key cytokines and chemokines that further modulate the inflammatory
      response. During the inflammatory response, ROS and RNS modulate phagocytosis,
      secretion, gene expression, and apoptosis. Under pathological circumstances such
      as acute lung injury and sepsis, excess production of ROS may influence vicinal
      cells such as endothelium or epithelium, contributing to inflammatory tissue
      injury. A better understanding of these pathways will help identify novel targets
      for amelioration of the untoward effects of inflammation.

PMID- 17189822
TI  - The cellular basis for diverse responses to oxygen.
AB  - Mammalian cells have divergent responses to varying oxygen levels. Cells exposed
      to low oxygen levels (hypoxia) activate the transcription factor hypoxia
      inducible factor-1 (HIF-1) as an adaptive response. Cells exposed to hypoxia do
      not undergo senescence or cell death and do not diminish ATP levels. By contrast,
      cells exposed to high oxygen levels (hyperoxia) undergo senescence and cell death
      and decrease their ATP levels, yet do not activate HIF-1. Despite these divergent
      responses with respect to senescence, cell death, metabolism, and gene
      expression, the signaling events in both systems are mediated by the generation
      of mitochondrial-derived reactive oxygen species (ROS). This perspective reviews
      the role of signaling through mitochondrial ROS in hypoxic and hyperoxic
      environments.

PMID- 17189823
TI  - The 'A's and 'O's of NADPH oxidase regulation: a commentary on "Subcellular
      localization and function of alternatively spliced Noxo1 isoforms".

PMID- 17189824
TI  - Subcellular localization and function of alternatively spliced Noxo1 isoforms.
AB  - Nox organizer 1 (Noxo1), a p47(phox) homolog, is produced as four isoforms with
      unique N-terminal PX domains derived by alternative mRNA splicing. We compared
      the subcellular distribution of these isoforms or their isolated PX domains
      produced as GFP fusion proteins, as well as their ability to support Nox1
      activity in several transfected models. Noxo1alpha, beta, gamma, and delta show
      different subcellular localization patterns, determined by their PX domains. In
      HEK293 cells, Noxo1beta exhibits prominent plasma membrane binding, Noxo1gamma
      shows plasma membrane and nuclear associations, and Noxo1alpha and delta localize
      primarily on intracellular vesicles or cytoplasmic aggregates, but not the plasma
      membrane. Nox1 activity correlates with Noxo1 plasma membrane binding in HEK293
      cells, since Noxo1beta supports the highest activity and Noxo1gamma and
      Noxo1alpha support moderate or low activities, respectively. In COS-7 cells,
      where Noxo1alpha localizes on the plasma membrane, the activities supported by
      the three isoforms (alpha, beta, and gamma) do not differ significantly. The PX
      domains of beta and gamma bind the same phospholipids, including phosphatidic
      acid. These results indicate that the variant PX domains are unique determinants
      of Noxo1 localization and Nox1 function. Finally, the overexpressed Noxo1
      isoforms do not affect p22(phox) localization, although Nox1 is needed to
      transport p22(phox) to the plasma membrane.

PMID- 17189826
TI  - Two different pathways are involved in peroxynitrite-induced senescence and
      apoptosis of human erythrocytes.
AB  - CO(2) changes the biochemistry of peroxynitrite basically in two ways: (i)
      nitrating species is the CO(3)(-) / ()NO(2) radical pair, and (ii) peroxynitrite
      diffusion distance is significantly reduced. For peroxynitrite generated
      extracellularly this last effect is particularly dramatic at low cell density
      because CO(3)(-) and ()NO(2) are short-lived and decay mostly in the
      extracellular space or at the cell surface/membrane. This study was aimed to
      distinguish between peroxynitrite-induced extra- and intracellular modifications
      of red blood cells (RBC). Our results show that at low cell density and in the
      presence of CO(2) peroxynitrite induced the oxidation of surface thiols, the
      formation of 3-nitrotyrosine and DMPO-RBC adducts, and the down-regulation of
      glycophorins A and C (biomarkers of senescence). Reactivation of glycolysis
      reversed only the oxidation of surface thiols. Without CO(2) peroxynitrite also
      induced the oxidation of hemoglobin and glutathione, the accumulation of lactate,
      a decrease in ATP, the clustering of band 3, the externalization of
      phosphatidylserine, and the activation of caspases 8 and 3 (biomarkers of
      apoptosis). The latter biomarkers were all reversed by reactivation of
      glycolysis. We hypothesize that cell senescence could (generally) be derived by
      irreversible radical-mediated oxidation of membrane targets, while the appearance
      of apoptotic biomarkers could be bolstered by oxidation of intracellular targets.
      These results suggest that, depending on extracellular homolysis or diffusion to
      the intracellular space, peroxynitrite prompts RBCs toward either senescence or
      apoptosis through different oxidation mechanisms.

PMID- 17189825
TI  - Glutathione protects cells against arsenite-induced toxicity.
AB  - To understand the role of glutathione (GSH) in the protection of cells from
      arsenite toxicity, we studied the mechanism of apoptotic cell death in cells
      genetically unable to synthesize GSH (GCS-2 cells). Arsenite stimulated an
      increase in protein ubiquitination in GCS-2 cells while the wild-type cells were
      unaffected. Arsenite treatment increased lipid peroxidation and induced
      ubiquitination of molecular chaperone Hsp90 and impaired its ability to bind
      cochaperone p50(Cdc-37) and client proteins Plk-1 and Cdk-4 in GCS-2 cells.
      Treatment with arsenite also partially inhibited proteasome activity in GCS-2
      cells. In these cells stably transfected with GFP(u) (a reporter consisting of a
      short degron fused to the COOH-terminus of GFP), intracellular fluorescence
      increased, suggesting the accumulation of GFP aggregates. GCS-2 cells underwent
      apoptosis accompanied by release of cytochrome c into the cytoplasm. Taken
      together, these data suggest that a possible mechanism of arsenite-induced
      apoptosis is the accumulation of ubiquitinated proteins and impairment of the
      protein degradative pathway. Further, protection from arsenite-induced
      ubiquitination is mediated by GSH and to a lesser extent by available reducing
      equivalents in the cells.

PMID- 17189827
TI  - Novel role of IL-6/SIL-6R signaling in the expression of inducible nitric oxide
      synthase (iNOS) in murine B16, metastatic melanoma clone F10.9, cells.
AB  - Inducible nitric oxide synthase (iNOS) has been shown to be frequently expressed
      in melanomas; up-regulation of this enzyme is though to be associated with tumor
      progression. In this study, we investigated whether diverse cytokines such as: IL
      6, TNF-alpha, IL-1beta, IFN-gamma and IL6RIL6 (a highly active fusion protein of
      the soluble form of the IL-6R (sIL-6R) and IL-6) enhance the iNOS gene expression
      in B16/F10.9 murine metastatic melanoma cells. An increase at iNOS expression and
      NO production was observed with the co-treatment of IL6RIL6 plus TNF-alpha. Gel
      shift and reporter gene analyses revealed that IL6RIL6 selectively activated AP
      1; while TNF-alpha increased the activities of both NF-kappaB and AP-1.
      Persistent activation of AP-1 was also seen in cells treated with IL6RIL6 plus
      TNF-alpha. Stimulation of cells with IL6RIL6/TNF-alpha resulted in the activation
      of mitogen-activated protein kinases (MAPK) such as c-Jun N-terminal kinase (JNK)
      and p38, and the abrogation by pretreatment with JNK or p38 MAPK inhibitor.
      IL6RIL6 or IL6RIL6/TNFalpha-inducible AP-1 binding increase was supershifted by
      anti-c-Jun or c-Fos antibodies, and the activation of c-Jun and c-Fos was
      dependent on JNK and p38, respectively. These results suggest that IL-6/sIL
      6R/gp130 complex signaling has an unexpected positive effect on iNOS gene
      expression through JNK/p38 MAPK mediated-AP-1 activation in melanoma cells.

PMID- 17189828
TI  - Increased hepatic telomerase activity in a rat model of iron overload: a role for
      altered thiol redox state?
AB  - Telomeres are repeated sequences at chromosome ends that are incompletely
      replicated during mitosis. Telomere shortening caused by proliferation or
      oxidative damage culminates in replicative arrest and senescence, which may
      impair regeneration during chronic liver injury. Whereas the effects of
      experimental liver injury on telomeres have received little attention, prior
      studies suggest that telomerase, the enzyme complex that catalyzes the addition
      of telomeric repeats, is protective in some rodent liver injury models. Thus, the
      aim of this study was to determine the effects of iron overload on telomere
      length and telomerase activity in rat liver. Mean telomere lengths were similar
      in iron-loaded and control livers. However, telomerase activity was increased 3
      fold by iron loading, with no change in levels of TERT mRNA or protein. Because
      thiol redox state has been shown to modulate telomerase activity in vitro,
      hepatic thiols were assessed. Significant increases in GSH (1.5-fold), cysteine
      (15-fold), and glutamate cysteine ligase activity (1.5-fold) were observed in
      iron-loaded livers, whereas telomerase activity was inhibited by treatment with N
      ethylmaleimide. This is the first demonstration of increased telomerase activity
      associated with thiol alterations in vivo. Enhanced telomerase activity may be an
      important factor contributing to the resistance of rodent liver to iron-induced
      damage.

PMID- 17189829
TI  - Catalase characterization and implication in bleaching of a symbiotic sea
      anemone.
AB  - Symbiotic cnidarians are marine invertebrates harboring photosynthesizing
      microalgae (named zooxanthellae), which produce great amounts of oxygen and free
      radicals upon illumination. Studying antioxidative balance is then crucial to
      understanding how symbiotic cnidarians cope with ROS production. In particular,
      it is suspected that oxidative stress triggers cnidarian bleaching, i.e., the
      expulsion of zooxanthellae from the animal host, responsible for symbiotic
      cnidarian mass mortality worldwide. This study therefore investigates catalase
      antioxidant enzymes and their role in bleaching of the temperate symbiotic sea
      anemone Anemonia viridis. Using specific separation of animal tissues (ectoderm
      and endoderm) from the symbionts (zooxanthellae), spectrophotometric assays and
      native PAGE revealed both tissue-specific and activity pattern distribution of
      two catalase electrophoretypes, E1 and E2. E1, expressed in all three tissues,
      presents high sensitivity to the catalase inhibitor aminotriazole (ATZ) and
      elevated temperatures. The ectodermal E1 form is responsible for 67% of total
      catalase activity. The E2 form, expressed only within zooxanthellae and their
      host endodermal cells, displays low sensitivity to ATZ and relative
      thermostability. We further cloned an ectodermal catalase, which shares 68%
      identity with mammalian monofunctional catalases. Last, 6 days of exposure of
      whole sea anemones to ATZ (0.5 mM) led to effective catalase inhibition and
      initiated symbiont expulsion. This demonstrates the crucial role of this enzyme
      in cnidarian bleaching, a phenomenon responsible for worldwide climate-change
      induced mass mortalities, with catastrophic consequences for marine biodiversity.

PMID- 17189830
TI  - An evolutionarily conserved 16-kDa thioredoxin-related protein is an antioxidant
      which regulates the NF-kappaB signaling pathway.
AB  - Thioredoxin (TRX) is generally a 12-kDa protein-disulfide reductase. Here, we
      report the discovery of a 16-kDa thioredoxin-related protein designated Cr-TRP16,
      from a "living fossil," the horseshoe crab (Carcinoscorpius rotundicauda). Cr
      TRP16 contains an atypical WCPPC catalytic motif and possesses the classical
      thiodisulfide reductase activity, as indicated by the insulin reduction assay.
      Furthermore, Cr-TRP16 can function as an antioxidant and protect against DNA
      nicking by reactive oxygen species. Overexpression of Cr-TRP16 regulated the
      transcription of NF-kappaB-dependent genes probably by enhancing NF-kappaB DNA
      binding activity, suggesting possible roles for Cr-TRP16 in modulating the NF
      kappaB signaling pathway. In vivo, the antioxidant pyrrolidine dithiocarbamate
      suppressed the expression of NF-kappaB-regulated genes such as IkappaB and
      inducible nitric oxide synthase. This further supports the notion that oxidative
      stress is also a regulatory factor of the NF-kappaB signaling pathway, a
      phenomenon which has been entrenched for several hundred million years.
      Furthermore, we demonstrated that the 16-kDa thioredoxins are evolutionarily
      conserved from Caenorhabditis elegans to human. Interestingly, thioredoxin-like
      6, a human homologue of Cr-TRP16, could also enhance NF-kappaB DNA-binding
      activity, suggesting that the regulatory role of the 16-kDa thioredoxins on NF
      kappaB is well conserved through evolution.

PMID- 17189831
TI  - Shear stress stabilizes NF-E2-related factor 2 and induces antioxidant genes in
      endothelial cells: role of reactive oxygen/nitrogen species.
AB  - We have previously reported that antioxidant response element (ARE)-regulated
      genes, such as heme oxygenase 1 (HO-1), sequestosome 1 (SQSTM1), and NAD(P)H
      quinone oxidoreductase 1 (NQO1), are induced in human umbilical vein endothelial
      cells (HUVEC) upon exposure to laminar shear stress. In the present study, we
      have confirmed a critical role for NF-E2-related factor 2 (Nrf2) in the induction
      of gene expression in HUVEC exposed to laminar shear stress. Although the mRNA
      levels of Nrf2 were unchanged during exposure to shear stress, the protein levels
      of Nrf2 were markedly increased. Small interfering RNA (SiRNA) against Nrf2
      significantly attenuated the expression of Nrf2-regulated genes such as HO-1,
      SQSTM1, NQO1, glutamate-cysteine ligase modifier subunit (GCLM), and ferritin
      heavy chain. Nrf2 was rapidly degraded in cells treated with cycloheximide under
      static conditions, but shear stress decreased the rate of Nrf2 degradation.
      Incubation with the thiol antioxidant N-acetylcysteine strongly inhibited both
      the Nrf2 accumulation and the expression of Nrf2-regulated genes such as HO-1,
      GCLM, and SQSTM1. Nitric oxide (NO) production was increased with the strength of
      shear stress but neither the inhibitor of endothelial NO synthase (eNOS) nor the
      siRNA against eNOS affected the expression of Nrf2-regulated genes. A xanthine
      oxidase inhibitor oxypurinol and the flavoprotein inhibitor diphenyleneiodonium,
      which inhibits NAD(P)H oxidase and mitochondrial respiratory chain, markedly
      suppressed the expression of these genes. Moreover, diphenylpyrenlphosphine, a
      reducing compound of lipid hydroperoxides, also significantly suppressed Nrf2
      regulated gene expression. Taken together, these findings suggest that shear
      stress stabilizes Nrf2 protein via the lipid peroxidation elicited by xanthine
      oxidase and flavoprotein mediated generation of superoxide, resulting in gene
      induction by the Nrf2-ARE signaling pathway.

PMID- 17189832
TI  - Antioxidant and antiplatelet effects of rosuvastatin in a hamster model of
      prediabetes.
AB  - The objectives of this study were to determine the relationships among Type II
      diabetes (T2DM)-dependent elevations in platelet-derived reactive oxygen species
      (ROS), platelet-surface protein disulfide isomerase (psPDI) NO-releasing
      activity, and platelet aggregation and to evaluate the efficacy of rosuvastatin
      in normalizing these parameters in primary cells derived from a hamster model of
      prediabetic insulin resistance induced by fructose feeding. Platelets from
      rosuvastatin-treated non-fructose-fed (NFF) and fructose-fed (FF) hamsters were
      analyzed for aggregability and psPDI-denitrosation activity. Platelets from NFF
      animals treated with xanthine/xanthine oxidase (X/XO) were assessed for the same
      parameters and primary aortic endothelial cells (AEC) cultivated with a range of
      [rosuvastatin] +/- mevalonate were analyzed for ROS production. Platelets from FF
      hamsters displayed statistically significant enhanced ROS production, diminished
      psPDI-mediated NO-releasing activity, and hyperaggregability. Suggestively,
      platelets from NFF animals treated with X/XO displayed characteristics similar to
      platelets from FF animals. Rosuvastatin elicited a normalizing effect on all
      parameters measured in platelets from FF animals. Further, ROS production in
      primary AEC from FF animals could be blunted to that of NFF animals by
      concentrations of rosuvastatin in the range of those achieved in the bloodstream.
      Diminished psPDI-dependent NO-releasing activity and increased initial
      aggregation rates of FF platelets may result from elevated vascular ROS
      production under conditions of insulin resistance. Normalization of ROS
      production and platelet aggregation by rosuvastatin indicates its potential use
      as a vasculoprotective agent.

PMID- 17189833
TI  - High superoxide dismutase and low glutathione peroxidase activities in red blood
      cells predict susceptibility of lung cancer patients to radiation pneumonitis.
AB  - Radiation pneumonitis is an unpredictable complication of radiotherapy for lung
      cancer and a condition which can cause significant morbidity. The ability to
      identify patients at a high risk of developing pneumonitis is critical, since it
      will enable the individualization of the treatment plan. Because the cytotoxic
      effect of radiation is propagated through reactive oxygen species (ROS) and ROS
      driven oxidative stress, the role of antioxidant defense systems in radiation
      pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a
      model, we demonstrated that the antioxidant response of the lung correlated well
      with that of red blood cells (RBC). We then proceeded to test whether differences
      of RBC antioxidant response would predict the pneumonitis development in
      patients. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase
      (CAT) activities and glutathione in RBC were measured at baseline and then weekly
      for 6 weeks of treatment in 15 eligible patients receiving concurrent chemo
      radiotherapy for unresectable stage III NSCLC. Striking differences were found in
      the antioxidant activities of RBC with respect to the pneumonitis development.
      Those who developed pneumonitis showed higher SOD and lower GPX activities at
      baseline compared to those who did not (3.7 vs 6.8 units/mg for median SOD, 16.5
      vs 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was
      displayed consistently throughout the treatment period. The sensitivity and
      specificity of pneumonitis prediction were further increased when the GPX/SOD
      ratio was analyzed (pretreatment P = 0.0046). Our results provide a strong
      rationale to monitor SOD and GPX activities of RBC to identify patients who are
      at risk of developing pneumonitis, and to implement a strategy of increasing the
      GPX/SOD ratio in order to lower the risk.

PMID- 17189834
TI  - Reactive oxygen species in in vitro pesticide-induced neuronal cell (SH-SY5Y)
      cytotoxicity: role of NFkappaB and caspase-3.
AB  - Oxidative stress has been implicated in pesticide-induced neurotoxicity, based on
      its role in the cascade of biochemical changes that lead to dopaminergic neuronal
      cell death. We have, therefore, examined the role of oxidative stress caused by
      the pesticides endosulfan and zineb in human neuroblastoma cells (SH-SY5Y) in
      culture. Upon treatment with 50-200 microM concentrations of either of these
      pesticides, SH-SY5Y cells generated both superoxide anion and hydrogen peroxide
      in a dose-and time-dependent manner. Mixtures of the pesticides significantly
      enhanced the production of these reactive oxygen species compared to individual
      pesticide exposures. Pesticide treatment decreased superoxide dismutase,
      glutathione peroxidase, and catalase activities in SH-SY5Y cells. Additionally,
      these pesticides induced lipid peroxide (thiobarbituric acid reactive products)
      formation in these cells. While both pesticides individually (at 100 microM)
      increased caspase-3 activity, cells exposed to a mixture of the pesticides
      exhibited significantly low levels of this enzyme, probably due to excessive
      necrotic cell death. Furthermore, exposure to these pesticides increased nuclear
      NFkappaB activity. Taken together, these findings suggest that the cytotoxicity
      of endosulfan and zineb, both individually and in mixtures may, at least in part,
      be associated with the generation of reactive oxygen species with concomitant
      increased expression of NFkappaB.

PMID- 17189837
TI  - Inhibition of S1P-induced angiogenesis, metastasis and inflammation by dietary
      polyphenols.

PMID- 17189836
TI  - Inhibition of S1P by polyphenols prevents inflammation and angiogenesis:
      NFkappaB, a downstream effector?

PMID- 17189838
TI  - Palpable masses in breast during lactation.
AB  - OBJECTIVES: Diagnosis of breast cancer is more difficult in pregnant and
      lactating women. In the present study, the value of different radiological
      methods has been evaluated. MATERIAL AND METHODS: Twenty-seven patients with
      palpable breast masses during the lactation period were evaluated. All masses
      were investigated in the clinical course as well as in ultrasound. If ultrasound
      demonstrated a suspicious lesion a mammogram was done. If clinical course,
      ultrasound, and mammography could not rule out breast cancer, MR mammography was
      done. RESULTS: Eighteen ultrasound-guided biopsies were done, revealing three
      cysts, seven hyperplasias/mastopathia, three cases of papilloma, and two
      carcinomas. The 18 mammograms were classified as BI-RADS 1 and 2 in nine cases,
      as BI-RADS 3 in seven case, as BI-RADS 4 in one cases, and as BI-RADS 5 in also
      one case. MR mammography was done in 9 cases revealing three BI-RADS 4 categories
      and one BI-RADS 5 category, all of them showed a malignant histology.
      CONCLUSIONS: The density of the lactating breast compromises breast cancer
      diagnosis. Ultrasound should be the method of choice. If possible mammography and
      MR mammography should be done after lactating period.

PMID- 17189835
TI  - Obesity increases the risk of UV radiation-induced oxidative stress and
      activation of MAPK and NF-kappaB signaling.
AB  - Obesity has been implicated in several diseases, including cancer; however, the
      relationship of obesity and susceptibility to ultraviolet (UV) radiation-caused
      skin diseases has not been investigated. As UV-induced oxidative stress has been
      implicated in several skin diseases, we assessed the role of obesity on UVB
      induced oxidative stress in genetically obese Lep(ob)/Lep(ob) (leptin-deficient)
      mice. Here, we report that chronic exposure to UVB (120 mJ/cm(2)) resulted in
      greater oxidative stress in the skin of obese mice in terms of higher levels of
      H(2)O(2) and NO production, photo-oxidative damage of lipids and proteins, and
      greater depletion of antioxidant defense enzymes, like glutathione, glutathione
      peroxidase, and catalase. As UV-induced oxidative stress mediates activation of
      MAPK and NF-kappaB signaling pathways, we determined the effects of UVB on these
      pathways in obese mice. Exposure of obese mice to UVB resulted in phosphorylation
      of ERK1/2, JNK, and p38 proteins of the MAPK family. Compared to wild-type mice,
      the obese mice exhibited higher levels of phosphorylation of these proteins,
      greater activation of NF-kappaB/p65, and higher levels of circulating
      proinflammatory cytokines, including TNF-alpha, IL-1beta and IL-6, on UVB
      irradiation. Taking these results together, our study suggests for the first time
      that obesity in mice is associated with greater susceptibility to UVB-induced
      oxidative stress and therefore may be a risk factor for skin diseases associated
      with UVB-induced oxidative stress.

PMID- 17189839
TI  - Frequency of hepatic contour abnormalities and signs of portal hypertension at CT
      in patients receiving chemotherapy for breast cancer metastatic to the liver.
AB  - PURPOSE: This study aimed to determine the frequency of hepatic contour
      abnormalities and signs of portal hypertension at serial CT in patients receiving
      chemotherapy for breast cancer metastatic to the liver. MATERIALS AND METHODS: We
      retrospectively identified 91 women with breast cancer metastatic to the liver
      who received chemotherapy and underwent serial CT at our institution between 1998
      and 2002. Two readers independently categorized hepatic contour abnormalities on
      the final CT examination as none, limited retraction, widespread retraction, or
      diffuse nodularity. Readers also recorded the development of hepatic atrophy or
      enlargement, ascites, portosystemic collateral veins, and splenomegaly.
      Interpretative discrepancies were resolved by consensus. Portal hypertension was
      defined as the presence of at least two of the following CT signs: simple
      ascites, portosystemic collateral veins, and splenomegaly. RESULTS: After a
      median follow-up interval of 15 months (range, 1-46), hepatic contour
      abnormalities were seen in 68 of 91 patients (75%) and consisted of limited
      retraction (n = 42), widespread retraction (n = 10), or diffuse nodularity (n =
      16). Portal hypertension was found in 1 of 23 patients without contour
      abnormalities, in 1 of 42 patients with limited retraction, in none of 10
      patients with widespread retraction, and in 6 of 16 patients with diffuse
      nodularity (P < .01). CONCLUSION: Hepatic contour abnormalities commonly develop
      at serial CT in patients undergoing chemotherapy for breast cancer metastatic to
      the liver and may be accompanied by signs of portal hypertension; the latter are
      particularly, but not exclusively, associated with the development of diffuse
      hepatic nodularity.

PMID- 17189840
TI  - How image quality can be improved: our experience with multidetector computed
      tomography coronary angiography.
AB  - PURPOSE: The objective of this study was to investigate the factors that may
      influence image quality on multidetector computed tomography (MDCT) coronary
      angiography (CA). MATERIALS AND METHODS: Two hundred twenty-four consecutive
      patients (161 men and 63 women; mean age, 52 years; age range, 34-76 years)
      evaluated with MDCT CA were included in the study. The evaluation of the quality
      of the patients' images was mainly based on the contrast material phase (early
      phase, optimal phase, or late phase) and the level of stepladder artifact (none,
      acceptable, or unacceptable). In addition, factors such as patient selection,
      patient preparation, scanning, processing, and steps of analysis, which may be
      affecting the quality of a final image, were examined independently. RESULTS:
      Patients who could not achieve sufficient breath-holding despite multiple breath
      exercises, those with a calcium score of 500 or higher, those with a heart rate
      greater than 90 bpm after metoprolol administration (because of shortening of the
      diastolic phase in the most still period), and those whose scanning was not
      completed were excluded from the study. The results for the remaining 224
      patients were evaluated. Based on the contrast phase, there were 66 (29.5%)
      patients in the first group (early), 93 (41.5%) in the second group (optimal),
      and 65 (29%) in the third group (late). Among the 224 patients, the images of 152
      (67.9%) had no stepladder artifact, those of 67 (29.9%) were of acceptable image
      quality, and those of 5 (2.2%) were of unacceptable image quality. CONCLUSION: It
      is important to obtain high-quality images to achieve correct interpretation with
      coronary artery CT angiography. This study aimed to describe a technique
      performed on 224 patients based on an array of factors ranging from patient
      selection to postprocessing. The results show that patient selection, cooperation
      with the patient, and breath-holding exercises play a very important role in
      obtaining the best images. In addition, a proper scanning technique (e.g.,
      placement of electrocardiographic electrodes and contrast material phase) and
      postprocessing (e.g., reconstruction interval) may also contribute to obtaining
      high-quality images.

PMID- 17189841
TI  - Flat-panel-detector-based volumetric CT: performance evaluation of imaging for
      skeletal structures of small animals in comparison to multislice CT.
AB  - OBJECTIVES: The aim of this study was to compare the image performance of silicon
      based flat-panel-detector-based volumetric computed tomography (fpVCT) to
      multislice spiral computed tomography (MSCT) for the visualization and detail
      detectability of skeletal structures in rodents of different development stages.
      MATERIALS AND METHODS: Rodents of different development stages were imaged with
      fpVCT (GE prototype with circular gantry with two 1024 x 1024, 200-microm pixel
      size, amorphous silicon/Cesium lodid (Csl) flat-panel detector) and eight-slice
      MSCT (LightSpeed Ultra). Imaging parameters (80 kVp, 100 mA) and the position of
      the rodents were identical in both techniques. Image quality, detail
      detectability, and contour of skeletal structures were judged by two observers in
      consensus using a 4-point scale (1 = unsatisfactory...4 = good). Findings were
      displayed and evaluated in axial slices, multiplanar reconstructions (MPR),
      maximum intensity projections (MIP) and volume rendering technique (VRT) in both
      modalities. Mean and standard of error of mean were calculated. RESULTS: In axial
      slices, visualization and detail detectability of very subtle skeletal
      structures, e.g., the basis of the skull was better in fpVCT than in MSCT (4 vs.
      2 points). The MPRs of fpVCT showed less artifacts and more details than those of
      the MSCT. The MIPs and VRTs of the fpVCT demonstrated best image quality in all
      rodents of different development stages, whereas MSCT showed significant
      artifacts. CONCLUSION: fpVCT outperformed MSCT in imaging of small rodents. Due
      to the truly isotropic volume data set with high spatial resolution, fpVCT is a
      powerful tool in evaluating detailed skeletal structures.

PMID- 17189842
TI  - Radiology-Pathology Conference: Colonic schwannoma.
AB  - We report the radiology and pathology findings on a patient with colonic
      schwannoma, and review the literature on this very rare tumor.

PMID- 17189843
TI  - Littoral cell angioma.
AB  - Littoral cell angioma (LCA) is an extremely rare primary splenic tumor. There are
      few MRI and scintigraphic characteristics described. These characteristics may be
      most helpful in differentiating LCA from other primary vascular tumors. We
      present a 54-year-old woman found on CT to have a 7-cm mass within an enlarged
      spleen. LCA was diagnosed by ultrasound (US)-guided biopsy. She was successfully
      treated with laparoscopic splenectomy. The CT, MRI, US, and Tc99m-RBC scan
      characteristics are described along with histologic and immunohistochemical
      correlation.

PMID- 17189844
TI  - Paraganglioma of the sphenoid sinus: case report and review of literature.
AB  - We report a case of a 41-year-old woman who presented with occasional hemoptysis
      and hoarseness. Imaging showed a mass primarily in the sphenoid sinus but also
      extending into the right posterior ethmoid sinus and nasopharynx. Histology
      showed this mass to be a paraganglioma. We describe its computed tomography and
      magnetic resonance imaging findings, and we discuss the differential diagnosis
      and treatment.

PMID- 17189845
TI  - Isolated pericardial hydatid cyst in an asymptomatic patient: a remark on its
      radiologic diagnosis.
AB  - Cardiac hydatid cyst disease is uncommon, representing approximately 0.2% to 2%
      of all cyst-related cases. Cardiac hydatid cysts are found mostly within the
      myocardium. Most cardiac hydatid cysts are located in the interventricular septum
      or in the left ventricular wall. Only few cases of pericardial location have been
      reported; isolated pericardial hydatid cysts are especially extremely rare.
      Patients with a cardiac hydatid cyst are usually asymptomatic. We present the
      case of an asymptomatic patient with isolated pericardial hydatid cyst disease
      and discuss the role of chest X-rays in the incidental diagnosis of this
      condition.

PMID- 17189846
TI  - Radiological findings in Birt-Hogg-Dube syndrome: a rare differential for
      pulmonary cysts and renal tumors.
AB  - Birt-Hogg-Dube syndrome is a rare disorder characterized by cutaneous hair
      follicle tumors, pulmonary cysts, and renal tumors. We report a case of a 63-year
      old male patient with this syndrome. The radiological findings seen with this
      syndrome are described. Radiologists should be aware of and able to recognize
      this syndrome.

PMID- 17189847
TI  - Inferior vena cava obstruction due to cecum adenocarcinoma.
AB  - In this paper, we report the radiologic findings of cecal adenocarcinoma with
      caval invasion in a 60-year-old man. Caval invasion was confirmed by
      ultrasonographically guided fine-needle aspiration biopsy and by surgery. To our
      knowledge, this is the first case report demonstrating malignant caval thrombus
      due to colon cancer. In addition, we suggest that fine-needle aspiration biopsy
      may be helpful for prompt diagnosis and treatment in such a case.

PMID- 17189848
TI  - A case of liver sarcoidosis mimicking cirrhosis.
AB  - Although autopsy series report liver granulomas in up to 70% of patients,
      computed tomography detection of hepatic and splenic lesions is described in 5%
      and 15% of sarcoidosis cases, respectively. A rather rare case of liver
      sarcoidosis mimicking macronodular cirrhosis is presented by this current
      article. Imaging findings in our patient were in compliance with the diagnosis of
      liver cirrhosis, although liver biopsy findings eventually revealed sarcoid
      granulomas located in the portal and lobular areas without fibrotic lesions.
      Histological and imaging modalities in liver sarcoidosis are discussed.

PMID- 17189849
TI  - Hepatic von Meyenburg complex simulating biliary cystadenocarcinoma.
AB  - Multiple bile duct hamartomas [von Meyenburg complex (VMC)] are benign liver
      malformations that include biliary cystic lesions, with congenital hepatic
      fibrosis being the cause of ductal plate malformations. This rare entity is
      usually isolated and detected incidentally in 0.6-5.6% of reported autopsy
      series. Its clinical significance is that it may be misdiagnosed as malignant
      liver disease. Imaging findings of VMC are nonspecific. We present a rare case of
      VMC in a patient who presented with epigastric and upper right abdominal pain,
      and jaundice of 2 months' duration. Ultrasonography, computed tomography, and
      magnetic resonance imaging showed a periportal multicystic mass simulating
      biliary cystadenoma/cystadenocarcinoma. The patient underwent laparotomy. A
      diagnosis of VMC was made after histopathologic examination of the wedge biopsy
      of the liver.

PMID- 17189850
TI  - Ectopic vaginal insertion of an obstructed duplicated ureter in an adult female:
      demonstration by magnetic resonance imaging.
AB  - The usual presentation of an ectopically inserted vaginal ureter is continuous
      dribbling of urine in an otherwise healthy girl. This case did not present with
      the usual symptomatology, as there was severe stenosis of the ectopically located
      ureteric orifice. Conventional imaging failed to show the vaginal insertion of an
      ectopic ureter. However, a magnetic resonance urogram readily depicted the
      collecting system from the kidney to the point of ureteric insertion.

PMID- 17189851
TI  - Report of two cases of uterus didelphys and rare ectopic (cornual and cervical)
      pregnancies.
AB  - Two cases of rare ectopic pregnancies are presented, both with underlying uterine
      didelphys anomaly. Uterine anomalies are a well-known predisposing factor for
      ectopic pregnancies. Detection of the uterine anomaly is crucial in the choice of
      treatment of an ectopic pregnancy as well as planning of future pregnancies.
      Magnetic resonance is helpful in diagnosing and defining the uterine anomaly
      (Saleem S. MR imaging diagnosis of uterovaginal anomalies: current state of the
      art. Radiographics 2003; 23:e13) that should be suspected by ultrasound.

PMID- 17189852
TI  - Congenital proximal radioulnar synostosis associated with bilateral hypoplasia of
      the scaphoid bone, bilateral os lunatotriquetrum, and anomalies of the
      carpometacarpal complex.
AB  - We describe a unique case of bilateral os lunatotriquetrum associated with
      bilateral hypoplasia of the scaphoid bone. On both sides, the medial carpi were
      in a single row. The capitate bone occupied the lunate position, whereas the
      lunatotriquetral bone was displaced ulnarly and tilted. The capitate thus
      articulated with the radius and metacarpal bones, consistent with carpal
      collapse. In addition, there was congenital proximal radioulnar synostosis on the
      left side.

PMID- 17189855
TI  - Methods in cell cycle research.

PMID- 17189853
TI  - Gnathodiaphyseal dysplasia.
AB  - Gnathodiaphyseal dysplasia (GDD) is an orthopedic condition involving cemento
      osseous lesions of jaw bones, sclerosis, bowing of tubular bones, and overall
      bone fragility. This is a case report of GDD in which an 18-year-old female
      presented with a several-year history of bony abnormalities of the jaw and long
      bones. Radiographs demonstrated endosteal thickening, bowing of long bones, and
      abnormalities of the skull. These findings, along with the patient's known
      maxillary region cementoma, led to a diagnosis of GDD.

PMID- 17189856
TI  - Analysis of cell cycle phases and progression in cultured mammalian cells.
AB  - Fluorescence activated cell sorting (FACS) analysis has become a standard tool to
      analyze cell cycle distributions in populations of cells. These methods require
      relatively large numbers of cells, and do not provide optimal resolution of the
      transitions between cell cycle phases. In this report we describe in detail
      complementary methods that utilize the incorporation of nucleotide analogs
      combined with microscopic examination. While often more time consuming, these
      protocols typically require far fewer cells, and allow accurate kinetic
      assessment of cell cycle progression. We also describe the use of a technique for
      the synchronization of adherent cells in mitosis by simple mechanical agitation
      (mitotic shake-off) that eliminates physiological perturbation associated with
      drug treatments.

PMID- 17189858
TI  - Measuring structural dynamics of chromosomes in living cells by fluorescence
      microscopy.
AB  - Mitotic and meiotic chromosomes are the compact packages that faithfully
      transport the genetic and epigenetic information to the following cell
      generations. How chromatin dynamically cycles between the decompacted interphase
      state that supports transcription and replication and the compacted state
      required for chromosome segregation is not understood. To address this long
      standing problem, the structure of chromatin should ideally be studied in the
      physiological context of intact cells and organisms. We discuss here, the
      contributions that live-cell imaging can and has made to the study of mitotic
      chromosome compaction and highlight the power and limitations of this approach.
      We review methodologies used and suggest that combinatorial approaches and
      developing new imaging technologies will be key to shedding light on this long
      standing question in cell biology.

PMID- 17189857
TI  - Mapping yeast origins of replication via single-stranded DNA detection.
AB  - Studies in th Saccharomyces cerevisiae have provided a framework for
      understanding how eukaryotic cells replicate their chromosomal DNA to ensure
      faithful transmission of genetic information to their daughter cells. In
      particular, S. cerevisiae is the first eukaryote to have its origins of
      replication mapped on a genomic scale, by three independent groups using three
      different microarray-based approaches. Here we describe a new technique of origin
      mapping via detection of single-stranded DNA in yeast. This method not only
      identified the majority of previously discovered origins, but also detected new
      ones. We have also shown that this technique can identify origins in
      Schizosaccharomyces pombe, illustrating the utility of this method for origin
      mapping in other eukaryotes.

PMID- 17189859
TI  - Measuring the rate of gross chromosomal rearrangements in Saccharomyces
      cerevisiae: A practical approach to study genomic rearrangements observed in
      cancer.
AB  - Gross chromosomal rearrangements (GCRs), including translocations, deletions,
      amplifications and aneuploidy are frequently observed in various types of human
      cancers. Despite their clear importance in carcinogenesis, the molecular
      mechanisms by which GCRs are generated and held in check are poorly understood.
      By using a GCR assay, which can measure the rate of accumulation of spontaneous
      GCRs in Saccharomyces cerevisiae, we have found that many proteins involved in
      DNA replication, DNA repair, DNA recombination, checkpoints, chromosome
      remodeling, and telomere maintenance, play crucial roles in GCR metabolism. We
      describe here the theoretical background and practical procedures of this GCR
      assay. We will explain the breakpoint structure and DNA damage that lead to GCR
      formation. We will also summarize the pathways that suppress and enhance GCR
      formation. Finally, we will briefly describe similar assays developed by others
      and discuss their potential in studying GCR metabolism.

PMID- 17189860
TI  - Analysis of kinetochore assembly and function in Caenorhabditis elegans embryos
      and human cells.
AB  - All eukaryotes rely on multi-protein assemblies, called kinetochores, to direct
      the segregation of their chromosomes in mitosis. The list of known kinetochore
      components has been growing rapidly in the post-genomic era: in animal cells,
      there are presently more than 80 proteins that show either exclusive or partial
      localization at kinetochores during mitosis. The future challenge is to elucidate
      how these proteins contribute to kinetochore structure, spindle microtubule
      attachment, regulation of microtubule dynamics, and the detection, signaling, and
      correction of microtubule attachment errors. Cultured human tumor cells,
      especially HeLa cells, are widely used for the study of kinetochores. Recently,
      the experimental advantages offered by the nematode Caenorhabditis elegans have
      been exploited for functional analysis of kinetochore components in the first
      embryonic division. Here, we discuss basic methods, largely based on fluorescence
      imaging, to study kinetochore structure and function in these two metazoan model
      systems.

PMID- 17189861
TI  - Silence is golden: combining RNAi and live cell imaging to study cell cycle
      regulatory genes during Caenorhabditis elegans development.
AB  - Much of the pioneering work on the genetics of cell cycle regulation was
      accomplished using budding and fission yeast. The relative simplicity of these
      single-celled organisms allowed investigators to readily identify and assign
      roles to individual genes. While the molecular mechanisms worked out in yeast are
      more or less identical to those operating in higher organisms, additional layers
      of control must exist in multicellular organisms to coordinate the timing of
      developmental events occurring in different cells and tissues. Here we discuss
      experimental approaches for studying cell cycle processes in the nematode
      Caenorhabditis elegans.

PMID- 17189862
TI  - Analysis of the cell division cycle in Drosophila.
AB  - Drosophila melanogaster presents in an unparalleled opportunity to study the
      regulation of the cell division cycle in the context of cellular differentiation,
      growth regulation and the development of a multicellular organism. The complexity
      of Drosophila cell cycles and the large number of techniques available can,
      however, be overwhelming. We aim to provide here (1) an overview of cell cycle
      regulation and techniques in Drosophila and (2) a detailed description of
      techniques we recently used to study embryonic mitoses.

PMID- 17189863
TI  - dSLAM analysis of genome-wide genetic interactions in Saccharomyces cerevisiae.
AB  - Analysis of genetic interactions has been extensively exploited to study gene
      functions and to dissect pathway structures. One such genetic interaction is
      synthetic lethality, in which the combination of two non-lethal mutations leads
      to loss of organism viability. We have developed a dSLAM (heterozygote diploid
      based synthetic lethality analysis with microarrays) technology that effectively
      studies synthetic lethality interactions on a genome-wide scale in the budding
      yeast Saccharomyces cerevisiae. Typically, a query mutation is introduced en
      masse into a population of approximately 6000 haploid-convertible heterozygote
      diploid Yeast Knockout (YKO) mutants via integrative transformation. Haploid
      pools of single and double mutants are freshly generated from the resultant
      heterozygote diploid double mutant pool after meiosis and haploid selection and
      studied for potential growth defects of each double mutant combination by
      microarray analysis of the "molecular barcodes" representing each YKO. This
      technology has been effectively adapted to study other types of genome-wide
      genetic interactions including gene-compound synthetic lethality, secondary
      mutation suppression, dosage-dependent synthetic lethality and suppression.

PMID- 17189865
TI  - Hypothesis testing via integrated computer modeling and digital fluorescence
      microscopy.
AB  - Computational modeling has the potential to add an entirely new approach to
      hypothesis testing in yeast cell biology. Here, we present a method for seamless
      integration of computational modeling with quantitative digital fluorescence
      microscopy. This integration is accomplished by developing computational models
      based on hypotheses for underlying cellular processes that may give rise to
      experimentally observed fluorescent protein localization patterns. Simulated
      fluorescence images are generated from the computational models of underlying
      cellular processes via a "model-convolution" process. These simulated images can
      then be directly compared to experimental fluorescence images in order to test
      the model. This method provides a framework for rigorous hypothesis testing in
      yeast cell biology via integrated mathematical modeling and digital fluorescence
      microscopy.

PMID- 17189864
TI  - Analyzing the ATR-mediated checkpoint using Xenopus egg extracts.
AB  - Our knowledge of cell cycle events such as DNA replication and mitosis has been
      advanced significantly through the use of Xenopus egg extracts as a model system.
      More recently, Xenopus extracts have been used to investigate the cellular
      mechanisms that ensure accurate and complete duplication of the genome, processes
      otherwise known as the DNA damage and replication checkpoints. Here we describe
      several Xenopus extract methods that have advanced the study of the ATR-mediated
      checkpoints. These include a protocol for the preparation of nucleoplasmic
      extract (NPE), which is a soluble extract system useful for studying nuclear
      events such as DNA replication and checkpoints. In addition, we describe several
      key assays for studying checkpoint activation as well as methods for using small
      DNA structures to activate ATR.

PMID- 17189866
TI  - Mathematical modeling as a tool for investigating cell cycle control networks.
AB  - Although not a traditional experimental "method," mathematical modeling can
      provide a powerful approach for investigating complex cell signaling networks,
      such as those that regulate the eukaryotic cell division cycle. We describe here
      one modeling approach based on expressing the rates of biochemical reactions in
      terms of nonlinear ordinary differential equations. We discuss the steps and
      challenges in assigning numerical values to model parameters and the importance
      of experimental testing of a mathematical model. We illustrate this approach
      throughout with the simple and well-characterized example of mitotic cell cycles
      in frog egg extracts. To facilitate new modeling efforts, we describe several
      publicly available modeling environments, each with a collection of integrated
      programs for mathematical modeling. This review is intended to justify the place
      of mathematical modeling as a standard method for studying molecular regulatory
      networks and to guide the non-expert to initiate modeling projects in order to
      gain a systems-level perspective for complex control systems.

PMID- 17189867
TI  - Rosiglitazone: safety and efficacy in combination with insulin in poorly
      controlled type 2 diabetes mellitus patients treated with insulin alone.
AB  - AIMS: To assess the safety and efficacy of rosiglitazone and insulin treatment in
      combination in poorly controlled insulin-treated type 2 diabetes mellitus (T2DM)
      patient. METHOD: In this prospective, open-labelled, nonrandomised study,
      rosiglitazone was added to the insulin therapy in T2DM patients with baseline
      HbA1c>or=7.5%. Patients were followed for 12 months. Insulin dosage was adjusted
      as necessary. RESULTS: Insulin and rosiglitazone combination was used in 53
      patients (29 male, 24 female) for 12 months. Baseline vs. 12-month results shown
      as mean+/-S.D.: HbA1c reduction 1.53% (9.82+/-1.12 vs. 8.29+/-1.45, P=.0001),
      insulin dosage reduction 10 U (74+/-34 vs. 64+/-34 U), percentage insulin dose
      reduction 13.53%, and weight gain 1.0 kg only (84+/-19.93 vs. 85+/-25.73 kg,
      P=.1). Systolic blood pressure 144+/-22.9 vs. 134+/-15.8 mm Hg (P=.03), total
      cholesterol 6.18+/-4.15 vs. 4.75+/-2.71 micromol/L, triglyceride 2.62+/-1.49 vs.
      2.07+/-1.44 micromol/L, and HDL cholesterol 1.43+/-0.71 vs. 1.63+/-0.36
      micromol/L (P=.02). Alanine transaminase actually reduced significantly from 26+/
      22 to 19+/-9 IU/L (P=.001). Improved glycaemic control was associated with
      favourable reduction in cardiovascular risk factors. Rosiglitazone was
      discontinued only in nine patients (weight gain-4, no improvement noticed-4,
      ankle swelling-1). No hepatotoxicity was observed. CONCLUSION:
      Rosiglitazone+insulin combination is safe and effective in inadequately
      controlled insulin-treated T2DM patients.

PMID- 17189868
TI  - The level of 2-h post-challenge glucose is an independent risk factor of carotid
      intima-media thickness progression in Korean type 2 diabetic patients.
AB  - OBJECTIVE: To evaluate the relationship between the metabolic abnormalities
      commonly associated with diabetes and the changes in carotid intima-media
      thickness (IMT) in Korean type 2 diabetic patients who do not have clinically
      manifest cardiovascular disease (CVD). DESIGN: In a prospective study, a total of
      152 type 2 diabetic patients were recruited from a group of outpatients at the
      Yonsei University Hospital. MATERIALS AND METHODS: The carotid IMTs of 152
      subjects with type 2 diabetes (mean age 63.5+/-7.0 years) were determined at
      baseline and after a mean follow-up time of 23.7+/-3.7 months. Fasting plasma
      glucose, serum total cholesterol (TC), serum triglyceride, high-density
      lipoprotein cholesterol (HDL-C), HbA1c, oral glucose tolerance test (OGTT)
      results for 2-h post-challenge glucose (2hPG), and blood pressure measurements
      were collected every 3 months and averaged. RESULTS: The highest quartiles of
      baseline C-peptide and homeostatic model assessment (HOMA) index showed more IMT
      progression than the lowest quartiles. The change in the mean IMT correlated with
      average values of HbA1c (r=.219, P=.007), the 2-h post-challenge glucose (r=.239,
      P=.003), HDL-C (r=-.228, P=.005), LDL-C (r=.175, P=.033), and non-HDL-C (r=.194,
      P=.016). Multiple regression analysis demonstrated that the independent risk
      factor for the mean IMT change in diabetic patients was the average 2hPG level
      (P=.004). The change in the mean IMT of those in the lowest quartile of average
      2hPG (<11.1 mmol/l) was 823+/-176 to 841+/-146 microm (P=.276). In the highest
      quartile (2hPG >15.3 mmol/l), however, the mean IMT increased from 794+/-127 to
      882+/-153 microm (P<.001). CONCLUSION: The 2hPG parameter among the various
      metabolic parameters exerts the greatest influence upon the prevention of carotid
      IMT progression in type 2 diabetic subjects. The level of 2hPG is an independent
      risk factor for the progression of carotid IMT in Korean type 2 diabetic
      patients.

PMID- 17189869
TI  - Bedside neuropathy disability score compared to quantitative sensory testing for
      measurement of diabetic neuropathy in children, adolescents, and young adults
      with type 1 diabetes.
AB  - BACKGROUND: While regular yearly screening for diabetic retinopathy and
      nephropathy is well established in patients with diabetes mellitus, there are no
      standardized diagnostic tests for diabetic peripheral neuropathy (DPN). In the
      present study, we compared the bedside neuropathy disability score (NDS) with
      quantitative sensory testing (QST) for screening for DPN in youth with type 1
      diabetes mellitus. METHODS: One hundred sixty-six patients aged 10 to 34 years
      (median 21 years) were evaluated for DPN by the NDS and QST. Quantitative sensory
      testing was also done in 43 healthy, age-matched controls. Diabetic peripheral
      neuropathy grade by both methods was correlated with disease-related variables.
      RESULTS: On QST, the diabetic group had significantly higher mean scores for
      vibration (P<.001) and warm sensation (P<.01) than controls, and lower scores for
      cold sensation (P<.05); however, there was a great degree of overlap. The NDS
      significantly correlated with the vibration threshold, but not with the warm and
      cold thresholds. The NDS significantly correlated with age at testing, diabetes
      duration, and long-term and current HbA1c levels (P<.001), and with the presence
      of microalbuminuria and diabetic retinopathy (P<.001). Analysis of the QST
      variables yielded significant correlations of vibration and warm sensation with
      age at testing (P<.001, P<.05, respectively) and of vibration with diabetes
      duration (P<.001) and retinopathy (P=.05); none of the quantitative tests
      correlated with glycemic control. CONCLUSIONS: The stronger association of the
      NDS with glycemic control and other microvascular complications compared to the
      perception thresholds, and its shorter time of performance and lack of costly
      equipment, may make the NDS the preferred method for measuring DPN in this
      population.

PMID- 17189870
TI  - Premeal insulin lispro plus bedtime NPH or twice-daily NPH in patients with type
      2 diabetes: acute postprandial and chronic effects on glycemic control and
      cardiovascular risk factors.
AB  - OBJECTIVE: Two insulin regimens were used to explore acute and chronic
      postprandial changes in glycemia, lipemia, and metabolic markers associated with
      increased risk of cardiovascular disease. METHODS: An open-label, randomized, two
      period crossover study (12 weeks/period) compared a prandial regimen [premeal
      insulin lispro+bedtime neutral protamine Hagedorn (NPH)] with a basal regimen
      (twice-daily NPH). There were 30 patients (12 women and 18 men; mean age=61
      years) with type 2 diabetes mellitus (mean duration=16 years) who were randomized
      after a 2-month lead-in with twice-daily NPH treatment. A standard lunch test
      meal developed according to each patient's caloric needs was administered at the
      end of each treatment period. RESULTS: Insulin lispro was associated with
      significantly lower postprandial glucose (area under the curve0-5 h=43.54 vs.
      57.65 mM/h; P<.001), elevated insulin concentrations, and acutely altered lipid
      fractions that included an early decrease followed by an increase in free fatty
      acids, lower triglycerides, elevated total cholesterol, elevated low-density
      lipoprotein cholesterol (LDL), and elevated high-density lipoprotein cholesterol.
      After 12 weeks of treatment, insulin lispro+bedtime NPH reduced hemoglobin A1c
      (HbA1c; mean+/-SE=7.6+/-0.2 vs. 8.2+/-0.2%; P<.001) without increasing
      hypoglycemia or insulin dose as compared with twice-daily NPH. Furthermore,
      treatment with the prandial insulin regimen resulted in lower total cholesterol,
      lower LDL cholesterol, and lower oxidized LDL. CONCLUSION: Improved postprandial
      glycemic control, as observed in a regimen containing both prandial insulin
      lispro and NPH as the basal insulin, is associated with significantly lower HbA1c
      and acute modulation of lipid fractions after a test meal. These biochemical
      modifications may potentially have a favorable impact on cardiovascular risk in
      patients with type 2 diabetes mellitus.

PMID- 17189871
TI  - Genetic association analysis of the adiponectin polymorphisms in type 1 diabetes
      with and without diabetic nephropathy.
AB  - OBJECTIVE: Adiponectin [adipocyte C1q and collagen domain containing (ACDC)] is
      the most abundant adipose-specific protein. It is beneficial in that it improves
      insulin sensitivity and mitigates vascular damage, in addition to the possibility
      of it having anti-inflammatory properties. Clinical evidences demonstrate that
      serum adiponectin concentrations are increased in patients with type 1 diabetes
      (T1D) as well as in patients with microvascular complications. However, the
      genetic influence of the ACDC gene in T1D and diabetic microvascular
      complications is still unclear. The present study aims to evaluate the
      association of the ACDC genetic variation in T1D and diabetic nephropathy (DN).
      MATERIALS AND METHODS: Ten single nucleotide polymorphisms (SNPs) of the ACDC
      gene were genotyped in 432 T1D patients (of which, 196 had DN) and 187
      nondiabetic control subjects, who were all Swedish Caucasians, by using dynamic
      allele specific hybridization. RESULTS: Single-marker association analysis
      demonstrated that SNPs +45G15G(T/G) and +276(G/T) were strongly associated with
      T1D [P=.002, OR=1.855 (1.266-2.717) and P=.001, OR=1.694 (1.337-2.147)]. Further
      analysis for haplotypes of these two SNPs indicated that one of the common
      haplotype (T_G) was strongly associated with T1D [P<.001, OR=1.769 (1.430
      2.188)]. However, there was no significant difference in the allele frequencies
      of these two SNPs between the groups of T1D patients with nephropathy and the
      patients without nephropathy. CONCLUSIONS: The present study thus suggests that
      SNPs +45G15G(T/G) and +276(G/T) in the ACDC gene are associated with T1D but not
      with DN among Swedish Caucasians.

PMID- 17189872
TI  - Biomechanical and histomorphometric esophageal remodeling in type 2 diabetic GK
      rats.
AB  - Diabetes mellitus induces remodeling of the morphology and mechanical properties
      in the gastrointestinal tract. This study aimed to investigate the
      histomorphometric and biomechanical remodeling of esophagus in the diabetic type
      2 model Goto-Kakizaki (GK) rats. Five male diabetic GK rats and five male
      nondiabetic Wistar rats were used in this study. The mechanical test was
      performed in vitro where the whole esophagus was stretched to its in situ length
      and distended with pressures up to 10 cm H2O using a ramp distension protocol.
      The pressure and outer diameter were recorded. Circumferential stress (force per
      area) and strain (deformation) were computed from the diameter and pressure data
      using the zero-stress state as reference. The zero-stress state was obtained by
      cutting esophageal rings radially. This caused the rings to open up into a
      sector. The thickness, area, and the opening angle were measured from the
      digitized images. The layer circumference, thickness, and area were measured from
      histological slides. The collagen fraction was determined from histological
      slides with Van Gieson stain. Diabetes induced pronounced morphometric changes,
      e.g., the wall thickness and wall cross-sectional area significantly increased in
      the GK rats (P<.01). Histologically, the circumference, thickness, and area of
      the muscle layer and the collagen fraction of mucosa-submucosa layer were
      significantly increased in the GK rats (P<.01). The opening angle, outer residual
      strain, and residual strain difference to wall thickness ratio decreased
      significantly in the GK rats (P<.05 and P<.01). Furthermore, the circumferential
      stiffness of the esophagus is significantly higher in the GK rats than in the
      normal rats (P<.01). In conclusion, histomorphometric and biomechanical
      remodeling is a feature of the esophageal wall in GK rats.

PMID- 17189874
TI  - Effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion
      and surface expression of endothelial adhesion molecules induced by high glucose
      levels.
AB  - Neutrophil-endothelial adhesion is a crucial step in vascular inflammation and is
      recognized as a direct cause of serious atherosclerosis-mediated diseases. We
      previously demonstrated that high concentrations of glucose increased adhesion in
      a protein kinase C (PKC)-dependent manner within 48 h of administration by
      increasing the surface expression of endothelial adhesion molecules. In this
      study, we focused on the effects of histamine 2 receptor antagonists on
      endothelial-neutrophil adhesion and on the surface expression of endothelial
      adhesion molecules mediated by high glucose levels. Histamine 2 receptor
      antagonists have pleiotropic effects; they not only block the secretion of
      gastric acid, but also inhibit cell-cell adhesion, resulting in inhibition of
      metastasis. However, relevant mechanisms of action are not yet fully understood.
      Of three histamine 2 receptor antagonists (cimetidine, ranitidine, and
      famotidine), only cimetidine significantly attenuated adhesion mediated by 48-h
      incubation with 27.8 mM glucose. Cimetidine was found to decrease the surface
      expression of endothelial adhesion molecules intercellular adhesion molecule-1
      and P-selectin, but not E-selectin. To determine the effects of cimetidine on
      intracellular level, we examined the effects of cimetidine on PKC-induced changes
      in adhesion, as well as the effects of nitric oxide (NO) synthase inhibitors on
      cimetidine. We found that NO synthase inhibitors reduced the inhibitory effects
      of cimetidine, whereas cimetidine did not affect adhesion mediated by a PKC
      activator. These data suggest that cimetidine acts directly on endothelial cells
      to inhibit high-glucose-induced expression of adhesion molecules and neutrophil
      adhesion mediated by increasing endothelial NO production, but not by inhibiting
      PKC.

PMID- 17189873
TI  - Decreased production of inflammatory cytokines by circulating monocytes and
      dendritic cells in type 2 diabetic men with atherosclerotic complications.
AB  - Antigen-presenting cells (APCs) are involved in the development of
      atherosclerosis, whose complications represent the main cause of death in
      diabetic patients. Nevertheless, their role in atherogenesis is poorly
      understood. We compared the number of circulating monocyte and dendritic cell
      (DC) subsets as well as their capacity to produce inflammatory cytokines IL
      1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in type 2 diabetic men
      with (n=11) and without (n=44) chronic atherosclerotic complications.
      Identification and enumeration of peripheral blood (PB) lymphoid subsets,
      monocytes, myeloid (CD33strong+), CD16+, and plasmacytoid (CD33-/dim+) DCs as
      well as of their spontaneous and stimulated production of IL-1beta, IL-6, and TNF
      alpha were performed at the single-cell level by flow cytometry. Our results show
      that type 2 diabetic men with atherosclerotic complications display a
      significantly reduced spontaneous secretion of IL-6 by monocytes and CD16+ DCs
      and of TNF-alpha by CD16+ DCs as compared to patients without atherosclerotic
      complications. Spontaneous secretion of IL-1beta by monocytes and CD16 DCs and of
      IL-6 by CD33+ and plasmacytoid DCs was detected in patients without
      atherosclerotic complications but not in the other patients with complications.
      Taken together, these results indicate that type 2 diabetic men with
      atherosclerotic complications display both quantitatively and functionally
      impaired immunological responses by circulating APCs. The decreased patterns of
      inflammatory cytokine production by these cells may influence the inflammatory
      response mediated by APCs as well as the antigen-specific responses mediated by
      other cells such as T cells.

PMID- 17189875
TI  - High glucose alone, as well as in combination with proinflammatory cytokines,
      stimulates nuclear factor kappa-B-mediated transcription in hepatocytes in vitro.
AB  - Diabetes mellitus is frequently associated with coagulation disorders such as
      coronary heart disease and stroke. We aimed to clarify the molecular mechanism
      whereby hyperglycemia causes the procoagulant state. HuH7 human hepatocyte cells
      were treated with high glucose alone or in combination with proinflammatory
      cytokines, and the effects on the activity of the transcription factor nuclear
      factor kappa-B (NF-kappaB), which mediates the expression of acute-phase and
      coagulation-related genes, were examined. The results showed that increasing the
      medium glucose concentration from 3 to 24 mM significantly enhanced NF-kappaB
      luciferase activity by 40% in the presence of insulin. The effect was promoter
      specific and not mimicked by comparable hyperosmolality with L-glucose.
      Proinflammatory cytokines such as interleukin-1 and tumor necrosis factor-alpha
      (TNF-alpha) also stimulated NF-kappaB-dependent transcription and showed an
      additive effect with high glucose. Similar effects were obtained on acute-phase
      or coagulation/fibrinolysis-related gene promoters such as fibrinogen or
      plasminogen activator inhibitor-1, all of which are shown to have NF-kappaB
      mediated transcription. Finally, pretreatment of the cells with an antioxidant
      PDTC completely abolished the effect of high glucose and markedly attenuated that
      of TNF-alpha, suggesting the involvement of reactive oxygen species. These
      results suggest that (1) high glucose as well as proinflammatory cytokines have
      positive effects on NF-kappaB-mediated transcription in an additive manner and
      enhance coagulation-related gene expression and (2) the effects are mediated, at
      least partly, by the generation of oxidative stress and may be responsible for
      the high prevalence of thrombotic disorders in the metabolic syndrome with
      diabetes, hyperinsulinemia, obesity, and/or inflammation.

PMID- 17189877
TI  - The meaning and need for informed consent in research.

PMID- 17189876
TI  - Reversal of phrenic nerve palsy with topiramate.
AB  - A 57-year-old Caucasian man presented with diaphragmatic paralysis and type 2
      diabetes. He had severe orthopnea that remained unchanged for 1 year. He was
      later diagnosed with distal symmetric polyneuropathy and was started on
      topiramate. Within 26 weeks of treatment, the patient showed improvement in
      diaphragmatic function and regrowth of intraepidermal nerve fibers, accompanied
      by improvement in respiratory and peripheral neuropathy symptoms. Topiramate may
      prove to be an effective agent in the treatment of nonremitting diaphragmatic
      paralysis and regrowth of intraepidermal nerve fibers.

PMID- 17189878
TI  - Infective keratitis: a challenge to Indian ophthalmologists.

PMID- 17189880
TI  - Phenotypic and plasmid pattern analysis of Staphylococcus epidermidis in
      bacterial keratitis.
AB  - BACKGROUND: Staphylococcus epidermidis, a commensal of the conjunctival sac has
      been incriminated as the commonest etiological agent of bacterial keratitis.
      However, the pathogenic potential of this commensal organism is not clearly
      known. AIM: To determine any phenotypic, molecular markers of S. epidermidis
      pathogenicity in bacterial keratitis. MATERIALS AND METHODS: A total of 382
      corneal ulcer isolates of S. epidermidis and 87 S. epidermidis isolates from
      healthy eyes (controls) were studied. Speciation, biotyping and antibiotic
      sensitivity testing were performed by conventional methods. Tube slime and
      adherence tests were carried out by recommended techniques. Plasmid analysis was
      conducted by a standard protocol. STATISTICAL ANALYSIS: Chi-square test was
      employed for calculations. RESULTS: Out of 382 corneal ulcer isolates (Pathogens)
      284 (74.3%) belonged to biotypes I and II. Slime was detected in 164 (42.9%) of
      382 pathogens vs. 21 (24.1%) of 87 controls (P<0.001). Sixty-five (39.6%) of 164
      slime positive isolates were multidrug-resistant as compared to only 49 (22.4%)
      of 218 slime negative isolates (P<0.001). A significantly higher number i.e,
      73.1% (120/164) of slime-producers possessed a 21 Kb plasmid in contrast to only
      53.2% (116/218) of nonslime-producers (P<0.001). Presence of this plasmid had a
      statistical correlation of low significance with multidrug resistance (P=0.04).
      One hundred and seventy-two (45.0%) of 382 pathogens and 24 (27.6%) of the 87
      controls were adherent to artificial surfaces (P=0.003) and the majority of the
      adherent organisms (99/172, 57.6%) were slime producers (P<0.001). CONCLUSIONS:
      Slime was associated with multidrug resistance in corneal ulcer isolates of S.
      epidermidis. The 21 Kb plasmid could determine virulence as it was responsible
      for slime production and adherence.

PMID- 17189881
TI  - Activity of newer fluoroquinolones against gram-positive and gram-negative
      bacteria isolated from ocular infections: an in vitro comparison.
AB  - BACKGROUND: To determine the antibacterial activity of newer fluoroquinolones and
      compare their activity between ciprofloxacin-susceptible and resistant bacterial
      isolates from patients with keratitis and endophthalmitis. MATERIALS AND METHODS:
      The minimum inhibitory concentration (MIC) of ciprofloxacin, ofloxacin,
      levofloxacin, gatifloxacin and moxifloxacin was determined for 123 bacterial
      isolates, using E test. Among the 123 isolates, 68 were gram-positive
      (Staphylococcus spp, Streptococcus spp, Corynebacterium spp, Bacillus spp.) and
      55 were gram-negative (Pseudomonas aeruginosa). The bacterial isolates were
      divided into three groups: susceptible/intermediate/resistant to ciprofloxacin.
      The MIC values for various fluoroquinolones were compared between the three
      groups and between gram-positive and gram-negative bacteria. RESULTS: For gram
      positive isolates, median MICs of fourth generation fluoroquinolones were lower
      than second generation. The median MIC was lowest for gatifloxacin and
      moxifloxacin (0.094 mg/ml) in ciprofloxacin-susceptible isolates of gram-positive
      bacteria. For ciprofloxacin-susceptible gram-negative bacteria, the median MIC of
      ciprofloxacin (0.19 mg/ml) was significantly lower than ofloxacin, levofloxacin,
      gatifloxacin and moxifloxacin (1.5, 0.5, 0.5 and 2 mg/ml respectively).
      Ciprofloxacin-resistant isolates of gram-positive bacteria showed higher MIC of
      levofloxacin, moxifloxacin and gatifloxacin though they remained susceptible to
      them. None of the fluoroquinolones were effective against ciprofloxacin-resistant
      gram-negative bacteria. Overall, for gram-positive bacteria, median MICs of
      levofloxacin, moxifloxacin and gatifloxacin were below ciprofloxacin, the MIC of
      gatifloxacin and moxifloxacin was equal for gram-positive bacteria. CONCLUSIONS:
      Levofloxacin, gatifloxacin and moxifloxacin are statistically more effective
      against gram-positive bacteria, the latter two being equally effective.
      Ciprofloxacin remains the most effective fluoroquinolone against gram-negative
      bacteria.

PMID- 17189882
TI  - Comparison of clinical and microbiological profiles in smear-positive and smear
      negative cases of suspected microbial keratitis.
AB  - PURPOSE: To examine the hypothesis that initial smear examination results have a
      significant bearing on the management and outcome of suspected microbial
      keratitis. MATERIALS AND METHODS: One hundred and seventy consecutive patients
      with suspected microbial keratitis were included in a prospective nonrandomized
      comparative study and their detailed clinical and microbiological data (smears
      and cultures of corneal scrapings) were captured on a predesigned corneal ulcer
      database. Patients were divided into two groups: Group 1 included 68 patients
      with corneal scrapings negative in smears while Group 2 included 102 patients
      with corneal scrapings positive in smears. The two groups were compared for their
      clinico-microbiological profile, management and clinical outcome. The outcome was
      noted at three months. Fisher's exact test was applied for statistical analysis.
      RESULTS: Cultures were sterile in 57.3% of patients in Group 1 compared to 17.6%
      in Group 2. Scrapings that grew S. pneumoniae, gram-negative organisms, fungi and
      Acanthamoeba were more often positive in smears (18.6%, 11.8%, 19.6% and 2.9%
      respectively). While data on duration of prior treatment was not available, prior
      medication made no significant difference to smear results. More (79.3%) patients
      of Group 1 had small infiltrate size ( CONCLUSIONS: Initial smear examination
      helps in instituting specific therapy thereby improving the outcome in cases of
      microbial keratitis. Positive smears indicate greater severity of disease and
      prior medication may not be a significant cause of smear negativity.

PMID- 17189883
TI  - A pilot study on the infiltrating cells and cytokine levels in the tear of fungal
      keratitis patients.
AB  - AIM: To determine the cellular profile and cytokine levels in the tear fluid of
      fungal keratitis patients. MATERIALS AND METHODS: Tear samples were collected
      from six fungal keratitis patients (Group I) from active stages of the disease up
      to resolution. Tears collected from the following served as controls: uninfected
      fellow eye (Group II A) of Group I, patients undergoing cataract surgery (Group
      II B) and acute conjunctivitis (Group II C). The cellular profile was evaluated.
      Interleukines (IL-6, IL-8 and IL-1beta) were estimated using sandwich enzyme
      immunoassay. Statistical analysis was carried out using nonparametric two-sample
      median test. RESULTS: Polymorphonuclear leukocytes (PMN) were the predominant
      infiltrating cells in Group I. During the initial stages of fungal infection,
      levels of IL-6 and IL-8 in the tear samples were found to be significantly
      increased when compared with Group II A (P=0.019 for IL-6, P<0.001 for IL-8).
      This was also true for IL -8 (P=0.008) levels in Group I and Group II B). While
      IL-6 levels decreased significantly towards healing, IL-8 remained slightly
      elevated even after healing. These cytokines were at the base level in Group II
      A. Lymphocytes and PMN were present in equal proportions in Group II C, which
      showed elevated levels of cytokines but not to the extent of Group I. CONCLUSION:
      This horizontal study indicates that understanding the nature of the inflammatory
      response in the tears of fungal keratitis patients is of considerable interest
      and warrants further investigations.

PMID- 17189884
TI  - Evaluation of impression smear in the diagnosis of fungal keratitis.
AB  - PURPOSE: To evaluate and compare impression smear with the conventional
      mechanical corneal scraping by potassium hydroxide (KOH) method in the diagnosis
      of fungal keratitis. MATERIALS AND METHODS: Fifty consecutive cases of clinically
      suspected fungal keratitis were included. Under topical anesthesia, impression
      smear was obtained from the lesion, followed by the conventional mechanical
      scraping and both were transferred to sterile glass slides. The slides were
      examined under direct microscopy with KOH 10% wet mount. Impression smear KOH was
      compared with the scraping KOH and culture. RESULTS: The KOH smear was positive
      in 36 (72%) patients with impression smear technique and positive in 35 (70%)
      patients from corneal scrapings. Sensitivity of impression smear technique as
      compared to scraping was 97.14%, specificity 92.86%, positive predictive value
      94.4%, negative predictive value 92.86%, false positive rate 5.56%, false
      negative rate 7.14% and accuracy was 94%. As compared to culture, the sensitivity
      was 100%, specificity 46.67%, positive predictive value 55.56%, negative
      predictive value 100%, false positive rate 53.33%, false negative rate 0% and
      accuracy was 68%. CONCLUSION: Impression smear KOH examination is comparable to
      conventional mechanical corneal scraping KOH examination in making a tentative
      diagnosis of fungal keratitis and can be accurately relied upon for initiating
      anti-fungal therapy.

PMID- 17189885
TI  - A study of the spectrum of Acanthamoeba keratitis: a three-year study at a
      tertiary eye care referral center in South India.
AB  - PURPOSE: To determine the epidemiological and clinical characteristics of
      Acanthamoeba keratitis and also to determine the sensitivity and specificity of
      smears in the detection of Acanthamoeba. MATERIALS AND METHODS: A retrospective
      review of all culture-positive cases of Acanthamoeba keratitis seen between
      October 1999 and August 2002 was performed. Corneal scrapes were subjected to
      culture and microscopy using standard protocols. RESULTS: Out of 3183 consecutive
      patients with clinically diagnosed corneal ulcers evaluated, 33 (1.04%) were
      found to be due to Acanthamoeba. Twenty-four out of 33 (72.72%) were less than 51
      years of age (P<0.001). All patients were from rural areas (P<0.001) and 26
      (78.79%) of them were agricultural workers (P=0.031). All 33 had history of
      corneal injury (P<0.001) and 28 (84.85%) patients had injury with mud (P<0.001).
      All 33 (100%) patients had previous medical treatment (P=0.009) and 10 (30.3%)
      had used traditional eye medicines (P=0.183). A clinical pattern of ring
      infiltrate was characteristic in 15 (45.45%) patients. The diameter of the
      corneal ulcer was more than 6 mm in 27 (81.82%) eyes (P<0.001). Twenty-six
      (78.79%) patients had visual acuity of perception of light on initial
      presentation (P<0.001) and 24 (72.73%) had the same as their final visual
      outcome. The sensitivity of 10% potassium hydroxide (KOH) preparation was found
      to be higher (P<0.001) in the detection of Acanthamoeba cysts. CONCLUSION: The
      incidence of Acanthamoeba keratitis amongst the corneal ulcer patients was 1% in
      this setting and it was mainly due to corneal injury by mud. The KOH preparation
      is a sensitive diagnostic tool for the detection of Acanthamoeba. Delayed
      diagnosis or misdiagnosis and inappropriate antimicrobial therapy results in poor
      visual outcome.

PMID- 17189886
TI  - First report of evaluation of K-M media: a new corneal preservation medium.
AB  - PURPOSE: To analyze the outcome of keratoplasty performed using Kalevar-Majumdar
      (K-M) media, a new synthetic viscous medium for preservation of the cornea.
      MATERIALS AND METHODS: The K-M media-preserved donor eye balls were kept in a
      bottle in a refrigerator at 4 degrees C till the corneas were used. Forty-eight
      consecutive keratoplasty cases of pseudophakic bullous keratopathy with vision
      less than counting fingers at one meter and operated by a single surgeon have
      been analyzed. Corneal donor button of 7.5 mm was used on the 7.0 mm recipient
      bed in all cases. Surgery was done with a standard technique. All the cases were
      examined daily for the first week and at the end of one month for graft clarity,
      epithelial defect and stromal edema. RESULTS: The K-M media-preserved corneal
      grafts remained clear at the end of the first week in 95.8% (46 of 48) cases and
      at the end of one month in 93.7% (45 of 48) cases. Donor epithelial haze cleared
      in 24 h in all cases. The stromal edema got cleared in the majority (91.7%, 44 of
      48) within 24 h. Epithelial defect was seen in only 10.4% (five cases). There was
      no primary graft failure. CONCLUSION: K-M medium, a new viscous, synthetic
      corneal preservation medium, is a safe (no primary donor failure) alternative to
      conventional liquid corneal preservation media. K-M media-preserved eyes appear
      to have better preserved corneal epithelium with faster achievement of graft
      clarity postoperatively.

PMID- 17189887
TI  - Medical students' perception on eye donation in Delhi.
AB  - Corneal transplantation remains a major treatment option for restoring sight
      among those suffering from corneal blindness. The number of corneal transplants
      done is far less than the actual requirement in India. This is largely due to the
      inadequate numbers of corneas collected. Medical students can be involved in the
      motivation of patients and relatives to pledge their eyes and to do grief
      counseling for donating eyes. The aim of the study was to assess the perception
      and willingness of 180 first-year medical students towards eye donation in Delhi.
      They were administered a pretested semi-structured questionnaire on eye donation.
      Data were analyzed using Epi-Info software package 6.04 version. The majority
      (99.4%) of students knew that eyes can be donated after death but only 41.1% knew
      that the ideal time of donation was within six hours of death. Most participants
      (87.2%) were willing to donate eyes. Nobility in the act of eye donation was the
      main motivational force for eye donation according to 85.5% of students.
      Perceived reasons for not pledging eyes by the people were: lack of awareness
      (32.7%), objection by family members (27.7%), unsuitability to donate because of
      health problem (17.7%) and the unacceptable idea to separate the eye from the
      body (15.5%). Mass media such as television, newspapers, magazines and posters
      were important sources of information on eye donation. Perceived reasons for not
      donating eyes need to be considered while creating awareness about eye donation
      in the community.

PMID- 17189888
TI  - Familial calcific band-shaped keratopathy: report of two new cases with early
      recurrence.
AB  - We report two siblings with the rare entity of familial calcific band-shaped
      keratopathy (BSK). Detailed ophthalmic and systemic investigations failed to
      reveal any underlying causative pathology. Topical disodium ethylenediamine
      tetraacetate (EDTA) was applied for 30 min to all four eyes. In addition the
      right eye of the younger sibling required a superficial keratectomy. An
      improvement in corneal clarity was seen in the immediate postoperative period in
      both siblings. Histopathology of the keratectomy specimen revealed linear
      extracellular sub-epithelial granular calcium deposits. However, an early
      recurrence was noted in all four eyes at four weeks postoperatively. We report
      the second instance in the English literature of this entity. Band-shaped
      keratopathy presenting without an obvious etiology merits a complete systemic and
      ophthalmic workup. Patients with familial idiopathic BSK could be cases with poor
      prognosis for treatment with EDTA due to an early recurrence of the disease.

PMID- 17189889
TI  - Unusual dendritic keratitis.
AB  - Bilateral pseudo-dendritic keratitis in infancy can be due to tyrosinemia, a rare
      metabolic disorder. Ocular involvement may be the earliest presenting
      manifestation of this disease. Early diagnosis is essential because dietary
      modifications can result in complete reversal of the manifestations of this
      disorder. This disease must be suspected in all cases of non-responsive dendritic
      keratitis in the pediatric age group, especially if it is associated with
      cutaneous lesions such as patmoplantar keratosis. Serum tyrosine levels must be
      done in these cases.

PMID- 17189890
TI  - Nocardia infection following phacoemulsification.
AB  - Infection of a self-sealing tunnel incision is a rare but vision-threatening
      complication of cataract surgery. We describe two cases of side port infection
      following an uneventful phacoemulsification. Nocardia was isolated in one case.
      Both the cases were worsening on medical treatment and were successfully treated
      by therapeutic keratoplasty.

PMID- 17189891
TI  - Bilateral Pseudomonas keratitis without predisposing factors.
AB  - Bilateral keratitis usually occurs in predisposed individuals such as contact
      lens wearers, those suffering from malnutrition and immunodeficiency or patients
      undergoing bilateral refractive corneal surgery. We report a 30-year-old man
      without any obvious predisposing factors who presented with complaints of pain
      and decreased vision in both eyes. Examination revealed corneal ulcers in both
      eyes, which on microbiological culture grew Pseudomonas aeruginosa. The patient
      underwent a therapeutic keratoplasty in the right eye while the left eye was
      managed medically. Bilateral Pseudomonas keratitis can develop in the absence of
      any obvious predisposing factors.

PMID- 17189892
TI  - Ulcerative keratitis associated with contact lens wear.
AB  - To review the microbiological profile of ulcerative keratitis associated with
      contact lens (CL)-wear, 35 patients with culture-proven CL-associated microbial
      keratitis were studied between September 1999 and September 2002. Corneal scrapes
      and CL-care products were collected and were subjected to microbiological
      evaluation. Gram-negative bacilli alone were recovered from the corneal scrapes
      of all 35 (100%) patients, all 70 (100%) CL storage case wells and also from CL
      care solution of six (17.14%) of the 35 patients. There was a significantly
      higher number of Pseudomonas aeruginosa (71.43%) isolated from eyes with CL
      related keratitis than other bacterial isolates (28.57%) (P<0.001). Microbial
      contamination of CL storage cases was a great risk for gram-negative bacterial
      infection among soft CL-wearers.

PMID- 17189893
TI  - Persistent corneal edema secondary to presumed dead adult filarial worm in the
      anterior chamber.
AB  - We present three cases of persistent corneal edema secondary to presumed dead
      adult filarial worms lying in the anterior chamber with their attachment to the
      endothelium. Two of them were initially diagnosed as descemet's fold with corneal
      edema. Two patients underwent penetrating keratoplasty and in one case, surgical
      removal was partly possible with clearing of cornea.

PMID- 17189894
TI  - Traumatic globe rupture after deep anterior lamellar keratoplasty.
AB  - We report a case of traumatic globe rupture following blunt trauma in the left
      eye of a 20-year-old male who had undergone deep anterior lamellar keratoplasty
      for keratonus. Prolapse of both, the crystalline lens and the vitreous was
      present through the inferior 180 degrees donor host junction. After
      repositioning, anterior vitrectomy and repair of graft host junction, the graft
      regained clarity in eight weeks and there was good visual recovery.

PMID- 17189895
TI  - Bilateral metastasis to the retina, choroids and optic nerve from breast cancer:
      a clinicopathological case.
AB  - A 39-year-old Asian woman, with a known history of breast cancer, presented with
      a gradual onset of painless reduction in vision in both eyes. Examination
      revealed visual acuity of counting fingers in the right eye and light perception
      in the left. There were subretinal lesions in the posterior poles of both eyes
      and retinal detachment in the left eye. Later she developed left proptosis and
      restriction in left ocular movement, most likely to be caused by metastatic
      extraocular spread. She subsequently died from disseminated metastatic disease.
      Histopathological examination confirmed tumor cells infiltrating the choroids,
      retina and optic nerve in both eyes. The tumor cells were arranged in lobular
      fashion and stained positively with Periodic Acid Schiff, suggesting the primary
      to be lobular adenocarcinoma type. Choroidal metastatic disease is common but
      bilateral retinal and optic nerve involvement with extraocular spread from breast
      cancer is rare.

PMID- 17189896
TI  - Aspergillus iris granuloma in a young male: a case report with review of
      literature.
AB  - Endogenous aspergillosis is a rare occurrence. Endogenous Aspergillus
      endophthalmitis is a rare but devastating infection usually associated with
      disseminated aspergillosis or with intravenous drug abuse. We report a case of an
      isolated Aspergillus iris granuloma in a young immunocompetent male patient with
      review of the literature.

PMID- 17189897
TI  - Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in
      aggressive posterior retinopathy of prematurity.
AB  - Aggressive posterior retinopathy of prematurity (formerly known as fulminate/type
      II/rush disease) occurs in zone 1 or posterior zone 2. Treatment involves
      extensive near confluent laser ablation of a large area of avascular retina.
      Anterior segment ischemia is a rare complication that can occur due to injury to
      the long posterior ciliary arteries in the horizontal meridians during aggressive
      posterior laser treatment. The outcome of this rare complication is very poor.
      This case describes a favorable outcome of intravitreal injection of bevacizumab
      (Avastin) in a case of anterior segment ischemia.

PMID- 17189898
TI  - The need of prediction of posterior capsular plaques.

PMID- 17189899
TI  - Long-term anatomical and visual outcome of vitreous surgery for retinal
      detachment with choroidal coloboma.

PMID- 17189900
TI  - Ocular motor nerve palsy.

PMID- 17189901
TI  - Retinal nerve fiber layer measurements by optical coherence tomography in Indian
      eyes.

PMID- 17189902
TI  - 25-gauge vitrectomy under topical anesthesia.

PMID- 17189903
TI  - Anterior luxation of rollable intraocular lens.

PMID- 17189904
TI  - Pinguecula masquerading as conjunctival melanoma.

PMID- 17189905
TI  - Recurrence of herpes simplex keratitis after azithromycin.

PMID- 17189906
TI  - First molecular data on the phylum Loricifera: an investigation into the
      phylogeny of ecdysozoa with emphasis on the positions of Loricifera and
      Priapulida.
AB  - Recent progress in molecular techniques has generated a wealth of information for
      phylogenetic analysis. Among metazoans all but a single phylum have been
      incorporated into some sort of molecular analysis. However, the minute and rare
      species of the phylum Loricifera have remained elusive to molecular systematists.
      Here we report the first molecular sequence data (nearly complete 18S rRNA) for a
      member of the phylum Loricifera, Pliciloricus sp. from Korea. The new sequence
      data were analyzed together with 52 other ecdysozoan sequences, with all other
      phyla represented by three or more sequences. The data set was analyzed using
      parsimony as an optimality criterion under direct optimization as well as using a
      Bayesian approach. The parsimony analysis was also accompanied by a sensitivity
      analysis. The results of both analyses are largely congruent, finding monophyly
      of each ecdysozoan phylum, except for Priapulida, in which the coelomate
      Meiopriapulus is separate from a clade of pseudocoelomate priapulids. The data
      also suggest a relationship of the pseudocoelomate priapulids to kinorhynchs, and
      a relationship of nematodes to tardigrades. The Bayesian analysis placed the
      arthropods as the sister group to a clade that includes tardigrades and
      nematodes. However, these results were shown to be parameter dependent in the
      sensitivity analysis. The position of Loricifera was extremely unstable to
      parameter variation, and support for a relationship of loriciferans to any
      particular ecdysozoan phylum was not found in the data.

PMID- 17189907
TI  - Intraspecific differentiation in the lesser Japanese mole in eastern Honshu,
      Japan, indicated by nuclear and mitochondrial gene analyses.
AB  - The lesser Japanese mole, Mogera imaizumii, recognized by Motokawa and Abe
      (1996), occurs in eastern Honshu, western Honshu and Shikoku. Mitochondrial and
      nuclear DNA were analyzed for mole samples from eastern Honshu to elucidate
      intraspecific differentiation. Analyses of sequences of the mitochondrial
      cytochrome b gene (Cytb) and of a restriction fragment length polymorphism of the
      nuclear 28S ribosomal RNA gene spacer (rDNA-RFLP) revealed two genetic types,
      partially corresponding to Hutterer's (1993) taxa, M. wogura (= M. imaizumii) and
      M. minor. Most samples showed either of two combinations of mitochondrial /
      nuclear gene types. However, two specimens showed a different combination. This
      incongruent combination of mitochondrial and nuclear genes might have derived, in
      part, from an introgression event between genetically differentiated populations
      after secondary contact during the evolutionary history of the lesser Japanese
      mole in eastern Honshu.

PMID- 17189908
TI  - Characterization of mouse tissue kallikrein 5.
AB  - Mouse tissue kallikreins (Klks) are members of a large, multigene family
      consisting of 37 genes, 26 of which can code for functional proteins. Mouse
      tissue kallikrein 5 (Klk5) has long been thought to be one of these functional
      genes, but the gene product, mK5, has not been isolated and characterized. In the
      present study, we prepared active recombinant mK5 using an Escherichia coli
      expression system, followed by column chromatography. We then determined the
      biochemical and enzymatic properties of purified mK5. mK5 had trypsin-like
      activity for Arg at the P1 position, and its activity was inhibited by typical
      serine protease inhibitors. mK5 degraded gelatin, fibronectin, collagen type IV,
      high-molecular-weight kininogen, and insulin-like growth factor binding protein
      3. Our data suggest that mK5 may be implicated in the process of extracellular
      matrix remodeling.

PMID- 17189909
TI  - Effects of BTS (N-benzyl-p-toluene sulphonamide), an inhibitor for myosin-actin
      interaction, on myofibrillogenesis in skeletal muscle cells in culture.
AB  - Actin filaments align around myosin filaments in the correct polarity and in a
      hexagonal arrangement to form cross-striated structures. It has been postulated
      that this myosin-actin interaction is important in the initial phase of
      myofibrillogenesis. It was previously demonstrated that an inhibitor of actin
      myosin interaction, BDM (2,3-butanedione monoxime), suppresses myofibril
      formation in muscle cells in culture. However, further study showed that BDM also
      exerts several additional effects on living cells. In this study, we further
      examined the role of actin-myosin interaction in myofibril assembly in primary
      cultures of chick embryonic skeletal muscle by applying a more specific
      inhibitor, BTS (N-benzyl-p-toluene sulphonamide), of myosin ATPase and actin
      myosin interaction. The assembly of sarcomeric structures from myofibrillar
      proteins was examined by immunocytochemical methods with the application of BTS
      to myotubes just after fusion. Addition of BTS (10-50 microM) significantly
      suppressed the organization of actin and myosin into cross-striated structures.
      BTS also interfered in the organization of alpha-actinin, C-protein (or MyBP-C),
      and connectin (or titin) into ordered striated structures, though the sensitivity
      was less. Moreover, when myotubes cultured in the presence of BTS were
      transferred to a control medium, sarcomeric structures were formed in 2-3 days,
      indicating that the inhibitory effect of BTS on myotubes is reversible. These
      results show that actin-myosin interaction plays a critical role in the process
      of myofibrillogenesis.

PMID- 17189910
TI  - Developmental stages and germ cell lineage of the loach (Misgurnus
      anguillicaudatus).
AB  - The staging of embryonic and larval development, and the germ cell lineage of the
      loach, Misgurnus anguillicaudatus, are described. Fertilized eggs were obtained
      by artificial insemination. For the convenience of detailed observation and
      photography of the external appearance, we use dechorionated embryos. Through a
      series of operations, these embryos were cultured at 20 degrees C in an
      incubator. Embryonic and larval development of the loach was divided into five
      periods: cleavage, blastula, gastrula, segmentation, and hatching. Stages were
      assigned within each of these periods. Developmental stages were determined and
      named by morphological features and somite number. The staging series were
      photographed and tabulated. The germ cell lineage was then elucidated by whole
      mount in situ hybridization of mRNA expression of the germ-cell-specific marker
      vasa and histological analysis. Primordial germ cells (PGCs) of the loach derived
      from the cleavage furrows of 8-cell stage embryos began proliferation in the late
      blastula period and migrated to the gonadal anlagen through a migration pathway
      similar to that of the zebrafish. However, it is characteristic of the loach that
      PGCs migrate a long distance and stay in the posterior part of the yolk-extension
      region.

PMID- 17189911
TI  - Winter hibernation and body temperature fluctuation in the Japanese badger, Meles
      meles anakuma.
AB  - This study examined seasonal changes in body weight, hibernation period, and body
      temperature of the Japanese badger (Meles meles anakuma) from 1997 to 2001. Adult
      badgers showed seasonal changes in body weight. Between mid-December and
      February, badger activity almost ceased, as the animals remained in their setts
      most of the time. Adult male badgers were solitary hibernators; adult females
      hibernated either alone or with their cubs and/or yearlings. The total
      hibernation period of Japanese badgers ranged from 42 to 80 days, with a mean
      length of 60.1 days. Japanese badgers did not always spend the winters in the
      same sett, although they seldom changed setts during hibernation. I equipped a
      male cub with an intraperitoneally implanted data logger to record its body
      temperature between November and April, while the cub hibernated with its mother.
      Over the winter, the body weight of the cub decreased from 5.3 kg to 3.6 kg, a
      weight loss of 32.1%, and its body temperature ranged from 32.0 to 39.8 degrees
      C. The mean monthly body temperature was 35.1 degrees C in December, 34.8 degrees
      C in January, 35.9 degrees C in February, 37.1 degrees C in March, and 37.4
      degrees C in April, so the monthly decrease in body temperature of this cub was
      not great. The results indicate that during hibernation, when body temperature is
      low, there is likely considerable economy of energy and a reduced demand for
      adipose reserves.

PMID- 17189912
TI  - Proximate mechanisms causing morphological variation in a turban snail among
      different shores.
AB  - In many benthic organisms with a planktonic larval stage, local populations have
      different morphology. Such difference may arise from some of the following
      proximate mechanisms. "Local recruitment (LR)": no larvae move between local
      populations, and segregated populations possess alleles coding for locally
      adaptive morphology. "Intragenerational selection (IS)": larvae move between
      local populations, and individuals with alleles for locally adaptive morphology
      survive after recruitment. "Phenotypic plasticity (PP)": larvae move between
      local populations and show phenotypic plasticity to adapt to a locality after
      recruitment. We examined which mechanism explains our finding that a planktonic
      developer Turbo coronatus coronatus (Gastropoda) had significantly longer spines
      on its shell on more exposed shores at scales of < 2 km. Experiments at Ishigaki
      Island, Okinawa, Japan, showed the following results. (a) Shorter- and longer
      spined populations occurring within 2 km showed non-significant low psi(ST)
      values (-0.0040 to 0.00095) for the mitochondrial DNA COI region. This suggests
      no segregation of the local populations, supporting the mechanisms IS and PP. (b)
      T. c. coronatus generated significantly longer spines 70 days after being
      transplanted to the habitat of a longer-spined population, supporting IS and PP.
      (c) Individuals caged in the sea for 79 days generated longer spines than
      individuals in the laboratory, supporting PP. In conclusion, shore-specific
      morphology of T. c. coronatus arises most likely from phenotypic plasticity and
      possibly from intragenerational selection.

PMID- 17189914
TI  - C-values of seven marine mammal species determined by flow cytometry.
AB  - C-values, which estimate genome size, have puzzled geneticists for years because
      they bear no relationship to organismal complexity. Though C-values have been
      estimated for thousands of species, considerably more data are required in order
      to better understanding genome evolution. This is particularly true for mammals,
      in which C-values are known for less than 8% of the total number of mammalian
      species. Among marine mammals, a C-value has been estimated only for the
      bottlenose dolphin (Tursiops truncatus). Thus examination of additional species
      of marine mammals is necessary for comparative purposes. It will enable a better
      understanding of marine mammal genome evolution, and it is also relevant to
      conservation, because larger genome size has been linked to increased likelihood
      of extinction in some plant and animal groups. Our study presents C-values of
      seven marine mammal species, including five cetacean species that are endangered
      to varying degrees. Similarly to the results for other groups, our results
      suggest that larger genome size in cetaceans is related to an increased
      likelihood of extinction.

PMID- 17189913
TI  - Cloning of putative uncoupling protein 1 cDNA in a cold-intolerant mammal, the
      house musk shrew (Suncus murinus).
AB  - The house musk shrew (Suncus murinus), or suncus, is a unique experimental
      animal. We recently showed that this mammal is cold intolerant and hypothesized
      that its sensitivity to cold is caused by low thermogenic activity in brown
      adipose tissue (BAT). Thermogenesis in BAT is performed by a unique mitochondrial
      protein, uncoupling protein 1 (UCP1). Interestingly, only eutherians possess
      UCP1, and some traits in the suncus resemble those in the Ucp1-ablated mouse,
      including cold intolerance, histology of BAT, and obesity resistance. In a
      previous study, we hypothesized that UCP1 may not be present in BAT of the suncus
      or may be dysfunctional. Therefore, we performed cDNA cloning of suncus Ucp1 and
      compared it to homologs from other species. The deduced amino acid sequence
      showed high similarity to other mammalian UCP1. Northern blot analysis revealed
      mRNA in BAT, as in other mammals. However, a difference in an amino acid residue
      was observed in an important residue for thermogenesis. Genomic sequence analysis
      showed that this difference existed in our two genetically distant laboratory
      colonies. These results suggest that cold intolerance in the suncus is derived
      from low thermogenic activity of UCP1 and may exist in wild house musk shrews.

PMID- 17189915
TI  - Identification of two forms of vitellogenin-derived phosvitin and elucidation of
      their fate and roles during oocyte maturation in the barfin flounder, Verasper
      moseri.
AB  - A new method for visualizing small and multiple phosvitins (Pvs) in oocytes from
      a marine teleost was developed by a combination of gel filtration, alkaline
      phosphatase treatment, and SDS-PAGE followed by silver staining. Three distinct
      Pv polypeptides having molecular masses of 15 kDa, 8 kDa, and 7 kDa were
      visualized in vitellogenic follicle extract of barfin flounder, Verasper moseri.
      N-terminal amino acid sequencing identified two different N-termini that fell
      into the PvA (7 kDa) and PvB (15 kDa and 8 kDa) groups, which were derived from
      two forms of vitellogenin (Vg), VgA and VgB, respectively. Analysis of time
      course change in phosphorus-rich peaks of gel chromatography fractions of
      follicle extracts from different maturational stages demonstrated a rapid
      degradation of Pvs during mid-phase of oocyte maturation. Quantitative analysis
      of free amino acids in maturing follicles revealed an increment of serine content
      but not of phosphoserine, indicating the occurrence of dephosphorylation
      concomitant with Pv degradation. Measurement of phosphatase activity in follicles
      and eggs at different maturational stages demonstrated a significant activation
      of phosphatase especially under acidic conditions. This suggested that Pv
      degradation and dephosphorylation are regulated by changes in ooplasm pH during
      oocyte maturation. Our results also suggested that the Pvs in barfin flounder
      vitellogenic oocytes bind to much lower amounts of calcium and magnesium than
      those of masu salmon, Oncorhynchus masou. This indicates that the Pvs in the
      barfin flounder, a marine teleost spawning its eggs in seawater, do not play a
      role in the transport and deposition of calcium and magnesium into oocytes.

PMID- 17189916
TI  - Phase responses in the circannual rhythm of the varied carpet beetle, Anthrenus
      verbasci, under naturally changing day length.
AB  - In the varied carpet beetle, Anthrenus verbasci, we examined the effects on the
      circannual pupation rhythm of a short-day or long-day pulse under naturally
      changing day length at a constant 20 degrees C. A short-day pulse for 4 weeks
      caused a prominent phase delay or advance under constant long days, but had
      little or no effect on the phase under naturally changing day length between 4
      August and 24 November. A long-day pulse for 4 weeks given under naturally
      changing day length caused a phase shift in the first pupation group, as under
      constant short days. A long-day pulse given on 4 August, 1 September, or 29
      September caused a phase delay, and a pulse given on 27 October or 24 November
      caused a phase advance. Pupation was least synchronous just before the transition
      from delaying to advancing. However, the magnitude of phase delays was much
      smaller under natural day length than under short days. In the second pupation
      group, larvae pupated at the same time as in the control experiment without a
      long-day pulse, and this result can be attributed to entrainment to the
      geophysical year by long days in spring and summer.

PMID- 17189917
TI  - Pehuencoris, a new genus of Cardiastethini (Heteroptera: Anthocoridae) from
      southern Argentina and Chile (Patagonia).
AB  - We describe the new genus Pehuencoris to include P. gurguliophagus n. sp. from
      southern Argentina and Chile (Patagonia). We illustrate the dorsal habitus and
      male genitalia, provide a complete description of the ostiolar peritreme and its
      microsculpture, and show a distributional map. We include comments on the biology
      and habits of the new species, and discuss relationships of the new genus to
      other genera of Cardiastethini.

PMID- 17189918
TI  - Taxonomical and morphological notes on two species of mudskippers, Periophthalmus
      walailakae and Periophthalmodon schlosseri (Teleostei: Gobiidae) from Singapore.
AB  - The mudskipper Periophthalmus walailakae is recorded from Singapore, where it was
      previously misidentified as Periophthalmodon schlosseri, with which it is
      syntopic. Periophthalmus walailakae is distinguished from its congeners by the
      following combination of characters: pelvic fins completely united and shaped
      like a disk, and first dorsal fin dark brown or black, with a rounded posterior
      edge and a white distal margin. This species most closely resembles Pn.
      schlosseri but has one row of teeth on the upper jaw, scales on the isthmus, and
      a different upper lip and jaw morphology. Contrary to an earlier report, scales
      are present on the snout, interorbital, and isthmus of Ps. walailakae. The two
      species can also be distinguished by size, external morphology, and body color
      patterns.

PMID- 17189919
TI  - [A case of primary biliary cirrhosis].

PMID- 17189920
TI  - [Roles of F-18 FDG PET or PET/CT for the evaluation of gastrointestinal
      malignancies].
AB  - 18F-FDG PET scan is an useful functional whole body imaging modality that images
      various types of malignancies with relative high sensitivity and specificity in a
      reasonably rapid time. It depicts a lesion based on abnormal glucose metabolism
      whereas CT detects malignant process mostly based on altered anatomy. In patients
      with gastric cancers, PET scan detects only less than 50% of early cancers and 62
      98% of advanced cancers. For initial T staging, anatomical imaging with a high
      spatial resolution is essential. There are a few studies on the prognostic
      significance of FDG uptake with inconsistent results. In spite of low sensitivity
      for lymph node staging, the specificity of CT and PET scan are very high, and the
      specificity of PET scan tends to be higher than that of CT. Detection of distant
      metastases on PET scan is dependent on tumor histology, degree of FDG uptake in
      primary tumors, sites of distant metastases, etc. There are only a few data
      available for the evaluation of recurrence detection and treatment responses
      using FDG PET scan. FDG PET scan has been used in the preoperative staging of
      colorectal cancer with some promising results. It seems to be the most useful in
      restaging recurrent tumors and selecting those patients who would benefit from
      surgery. PET scan has a potential value in assessing treatment responses after
      various combination of treatments in patients with colorectal cancer.

PMID- 17189921
TI  - [Clinical usefulness of fecal occult blood test as a screening method for
      asymptomatic patients with colon polyps].
AB  - BACKGROUND/AIMS: Detection of asymptomatic benign colon polyp is increasing
      because colonoscopy is widely used as a screening and diagnostic method. Fecal
      occult blood test is usually performed for the selection of patients requiring
      colonoscopy as well as mass screening for colon cancer. The aim of this study was
      to investigate the usefulness of fecal occult blood test performed prior to
      colonoscopy as a screening method of benign colon polyps. METHODS: Clinical
      characteristics of patients with polyps were evaluated according to the fecal
      occult blood test results in patients who underwent one-day fecal occult blood
      test and colonoscopic polypectomies from May 2003 to October 2004,
      retrospectively. RESULTS: A total of 942 colonoscopic polypectomies in 288
      patients were evaluated. Fecal occult blood tests were positive only in 32
      patients (11.1%). In univariate analysis, there was a significant difference in
      polyp size (p=0.02) and location (p=0.03) according to the presence of positive
      fecal occult blood tests. In addition, age of the patient (p=0.046), polyp size
      (mean, p=0.04; largest, p<0.01) and the number of polyps (p=0.045) were
      significantly different. However, in multivariate analysis, only polyp size
      larger than 20 mm was significantly related with positive fecal occult blood test
      with estimated odds ratio of 4.71. CONCLUSIONS: Fecal occult blood test has
      limitations as a screening test in asymptomatic patients with colon polyps,
      except for colon polyps larger than 20 mm in size.

PMID- 17189922
TI  - [Bamboo joint-like appearance of stomach in Korean patients with Crohn's
      disease].
AB  - BACKGROUND/AIMS: Bamboo joint-like (BJL) appearance is an endoscopic finding
      characterized by swollen longitudinal folds transversed by erosive fissures or
      linear furrows on the lesser curvature side of gastric body and cardia. It has
      been reported to be associated with Crohn's disease (CD). This study was aimed to
      evaluate the incidence of BJL appearance in Korean patients with CD. METHODS:
      From January to December in 2005, we performed esophagogastroduodenoscopy (EGD)
      in patients diagnosed as CD and ulcerative colitis (UC) in our hospital. Non
      inflammatory bowel disease (IBD) subjects with upper gastrointestinal symptoms
      who underwent EGD were consecutively enrolled during the same period. One
      endoscopist performed all the endoscopic examinations to avoid inter-observer
      variation. A dye-spraying technique with 0.4% indigocarmine was used to allow the
      detection of subtle changes during the endoscopic examination. RESULTS: A total
      of 21 patients with CD (mean age+/-SD, 40+/-15 yr; M/F, 13/8), 28 patients with
      UC (42+/-15 yr; 21/7), and 685 non-IBD subjects (49+/-14 yr; 354/331) were
      enrolled. EGD findings in CD patients were gastric erosions (11/21), chronic
      superficial gastritis (5/21), chronic atrophic gastritis (1/21), duodenal
      erosions or ulcers (2/21), and normal (2/21). Incidence of BJL appearance was
      significantly higher in patients with CD (47.6%, 10/21) than others (UC, 3.6%,
      1/28; non-IBD, 0.1%, 1/685) (p< 0.0001). Among patients with CD, incidence of BJL
      appearance was not significantly different according to the sex, status of H.
      pylori infection, Vienna classification for phenotype, medications or EGD
      findings. CONCLUSIONS: BJL appearance on the gastric body and cardia can be a
      diagnostic clue to CD.

PMID- 17189923
TI  - [Renal dysfunction after spontaneous bacterial peritonitis in cirrhosis:
      incidence and risk factors].
AB  - BACKGROUND/AIMS: Deterioration of renal function in patients with cirrhosis and
      spontaneous bacterial peritonitis (SBP) is the most sensitive predictor of in
      hospital mortality. It has been shown that high dose intravenous albumin in
      addition to antibiotics reduces the incidence of renal impairment and improve
      hospital survival in these patients. Besides, it is important to know which
      patients would benefit from albumin infusion. Therefore, we conducted a
      retrospective study to elucidate the incidence and risk factors of renal
      dysfunction in cirrhotic patients with SBP. METHODS: All medical records of 76
      consecutive episodes of SBP in 60 patients were analyzed. Renal dysfunction after
      SBP was defined as elevation of BUN >30 mg/dL or serum creatinine >1.5 mg/dL in
      patients without preexisting renal insufficiency, or elevation of more than 50%
      of the baseline level in patients with renal dysfunction at the diagnosis of
      infection. RESULTS: Of the 76 episodes, renal dysfunction was present in 31
      (40.8%). Age, concurrent use of diuretics, large volume paracentesis (LVP) with
      volume expander, initial BUN and creatinine level were significant risk factors
      on univariate analysis. Of these, age and LVP were independent risk factors on
      logistic regression model. CONCLUSIONS: Renal dysfunction occurs in 40.8% of
      hospitalized patients after SBP. Considering poor prognosis of patients with
      renal dysfunction in SBP, close monitoring of renal function is needed and high
      dose intravenous albumin with antibiotics should be used especially in the
      elderly and those with LVP.

PMID- 17189924
TI  - [Hepatitis B and C virus infection and liver dysfunction in patients receiving
      chemotherapy].
AB  - BACKGROUND/AIMS: Liver dysfunction and reactivation of hepatitis virus are well
      described complications in cancer patients who receive cytotoxic chemotherapy and
      may result in varying degrees of liver damage. However, there has been just few
      reports on such complications and on the preemptive use of lamivudine in Korea.
      The aims of this study were to determine the prevalence of hepatitis B and C
      virus infection and the incidence of liver dysfunction in patients with
      malignancies who receive chemotherapy, to determine the reactivation rate of
      hepatitis B virus (HBV) in those patients, to evaluate the effect of preemptive
      use of lamivudine in patients with HBV infection. METHODS: Among 1,477 patients
      who received chemotherapy due to various malignancies from January 2000 to June
      2005, 668 patients with incomplete viral studies or hepatitis related malignancy
      were excluded. A retrospective study was conducted by reviewing the medical
      records of remaining 809 patients. RESULTS: The overall prevalence rate of
      hepatitis B or C virus in patients receiving chemotherapy was 6.55% (53/809). The
      incidences of liver dysfunction was not significantly different between hepatitis
      virus positive group and negative group. Reactivation rate of hepatitis B or C
      virus after chemotherapy was 15% (6/40). In all patients who received lamivudine
      therapy, aspartate aminotransferase and alanine aminotransferase level were
      normalized and HBV DNA negativity achieved. CONCLUSIONS: The existence of
      hepatitis virus in patients receiving chemotherapy did not significantly
      influence the development of severe liver dysfunction, owing probably to the
      lamivudine therapy. Further prospective studies are required to ascertain the
      reactivation of hepatitis virus in patients receiving chemotherapy and the need
      for prophylactic lamivudine therapy in HBV positive patients.

PMID- 17189925
TI  - [Intraductal ultrasonography for the selection of self expandable metal stent in
      extrahepatic bile duct carcinoma].
AB  - BACKGROUND/AIMS: Endoscopic stent insertion with self expandable metal stent
      (SEMS) is one of the standard palliative treatments for the patients with
      unresectable bile duct carcinoma. The aim of this study was to determine whether
      detection of longitudinal spread of extrahepatic bile duct carcinoma by
      intraductal US (IDUS) would be helpful in the selection of metal stent for the
      palliative drainage in bile duct carcinoma. METHODS: Seventeen patients with
      histologically proven unresectable extrahepatic bile duct carcinoma who underwent
      endoscopic retrograde cholangiography with IDUS were included. Longitudinal
      cancer extension along the bile duct was determined and, then, compared with the
      cholangiographic image. The type and length of SEMS was selected based on IDUS
      findings. RESULTS: IDUS demonstrated more extensive tumor spread than ERC in 7 of
      17 (41.2%) patients with the hepatic side of strictures and in 7 of 16 (43.8%)
      patients with the duodenal side of strictures. Five of 17 (29.4%) patients have
      changed the plan of endoscopic biliary drainage with SEMS after IDUS. There was
      no early dysfunction associated with endoscopic biliary drainage. CONCLUSIONS:
      IDUS prior to biliary drainage would be useful in demonstrating longitudinal
      extension of extrahepatic bile duct carcinoma. It has a potential role in helping
      stent selection and identifying factors which predict early stent dysfunction.

PMID- 17189926
TI  - [Two cases of acute renal failure associated with non-fulminant acute hepatitis
      A].
AB  - Hepatitis A is generally regarded as a mild, self-limiting disease of the liver.
      Acute renal failure has rarely been reported in association with non-fulminant
      acute hepatitis A. Acute tubular necrosis is the most common form of renal injury
      in such patients. We recently experienced two cases of hepatitis A in which acute
      renal failure occurred early in the course of the illness and had a clinical
      course suggestive of acute tubular necrosis. In both patients, the clinical
      course of renal dysfunction was almost parallel to that of hepatic dysfunction.
      Hemodialysis was performed in patient 1 because of severe uremia despite
      maintaining urine output more than 2,000 mL per day. On the other hand,
      hemodialysis was not performed in patient 2 who showed a rapid recovery of renal
      dysfunction. The renal biopsy of patient 1 demonstrated typical findings of acute
      tubular necrosis on microscopy.

PMID- 17189927
TI  - [A case of splenic pseudocyst difficult to differentiate from splenic
      lymphangioma].
AB  - Splenic pseudocyst is a rare complication of abdominal trauma. Although it is
      rare, splenic pseudocyst is well-documented in the literature. According to the
      current classification, approximately 30% of all splenic cysts or pseudocysts
      result from direct abdominal trauma. In addition, chronic pancreatitis leads to
      change of nearby organs with possible acute and chronic complications including
      splenic lesions. This unusual complication can occur in both emergent and non
      emergent conditions. The useful diagnostic procedures to assess intrasplenic
      pseudocyst are sonogram, CT scan, splenic scan, and occasionally angiography.
      However, definite diagnosis of pseudocyst is possible only after splenectomy when
      the absence of epithelial lining is confirmed histologically. Splenic pseudocyst
      requires surgical resection. We experienced a 31-year-old man who confirmed of
      warmness in the left side of back with left upper quadrant abdominal pain for
      several months. First impression was splenic lymphangioma based on CT scan and
      sonogram finding. Splenectomy was performed. Microscopic examination revealed
      splenic pseudocyst with fibrous capsule without epithelial lining.

PMID- 17189928
TI  - [Two cases of phytobezoars treated by adminsitration of Coca-Cola by oral route].
AB  - Bezoars are concretions of foreign bodies found in the gastrointestinal tract. In
      the past, most common method for the treatment of bezoar was surgical management.
      However, the current treatment methods include chemical dissolution and
      endoscopic mechanical lithotripsy. There were few reports on the treatment of
      phytobezoars by nasogastric Cola lavage. However, there was no report succeeded
      by oral route alone. In our two cases, phytobezoars were treated by oral
      administration of Coca-Cola. Our patients drank 700-800 mL of Coca-Cola daily,
      and after two months, complete dissolutions of bezoars were achieved. We report
      two cases of phytobezoars completely treated by drinking Coca-Cola.

PMID- 17189929
TI  - [A case of hepatectomy for liver metastasis after pancreatoduodenectomy for
      carcinoma of ampulla of Vater].
AB  - After curative resection of carcinoma of ampulla of Vater, 5-year survival rate
      has been reported ranging from 40% to 60%. Two major causes of the treatment
      failure are local recurrence and liver metastasis. Liver metastases are often
      multiple and are associated with poor prognosis. There have been few reports on
      long-term survivors after hepatectomy for metastatic liver tumors from carcinoma
      of ampulla of Vater. We report a 42 year-old female patient with solitary hepatic
      metastasis from carcinoma of ampulla of Vater, which was successfully treated by
      hepatectomy 69 months after curative Whipple's operation. Histologic examination
      of the resected specimen had revealed stage IB moderately-differentiated,
      intestinal type adenocarcinoma (T2N0M0). Since neither local recurrence or
      distant metastasis were detected, the patient underwent liver segmentectomy.
      Histologic study confirmed the presence of metastatic liver tumor from carcinoma
      of ampulla of Vater. She is doing well without evidence of recurrence at 20
      months after hepatectomy.

PMID- 17189931
TI  - [Usefulness of fecal occult blood test as a colorectal cancer screening method].

PMID- 17189930
TI  - [A case of primary small cell carcinoma arising from the common bile duct].
AB  - Small cell carcinoma is usually seen in the lung, but rarely involves the
      gastrointestinal tract including biliary tract. A 65 year-old man was admitted
      because of obstructive jaundice. A smooth-surfaced round intraluminal mass with
      proximal bile duct dilatation was seen in the proximal common bile duct on
      endoscopic retrograde cholangiogram. Under the diagnosis of bile duct cancer,
      pylorus-preserving pancreatoduodenectomy was done. Pathology revealed a 2 cm
      sized small cell carcinoma in the proximal common bile duct and distal common
      hepatic duct. On immunohistochemical stain, the tumor cells were positive for
      neuroendocrine markers CD56 and synaptophysin. After surgery, the patient
      received 5 cycles of adjuvant chemotherapy with VIP (etoposide, ifosfamide, and
      cisplatin) regimen. However, the patient died of liver metastasis 12 months after
      the diagnosis. We report a case of extrapulmonary small cell carcinoma arising
      from the common bile duct.

PMID- 17189932
TI  - [Development of automatic analyses for star-shot images using computed
      radiography (CR)].
AB  - Recent progress in radiation therapy has been greatly enhanced in many facilities
      by the development of new machines for treatment, improved computer technology
      for radiotherapy treatment planning systems (RTPs), increased accuracy of
      radiation therapy such as stereotactic irradiation, and intensity-modulated
      radiation therapy (IMRT). Quality control (QC) of the isocenter, which has
      consisted of gantry rotation and limiting the radiation field, is important for
      greater accuracy of these radiation therapy technologies. Star-shot analyses
      using computed radiography (CR) for evaluation of the isocenter were employed in
      this study. Devices to support CR were created, and a method of automatically
      analyzing images obtained by the star-shot technique, which calculated the error
      (distance) from the isocenter and the incident beam angle, were developed. In
      terms of the accuracy of our method, the average maximum error was 0.33 mm (less
      than 2 pixels: 0.35 mm), the average absolute error and incident beam angle
      errors were 0.3 mm and 0.4 degrees at maximum and at one standard deviation (SD),
      respectively. In this study, the processing times were 16 sec at minimum, 152 sec
      at maximum, 18 sec at most frequencies, and 23.6 sec on average. In conclusion,
      it was considered that our newly developed method for analyzing star-shot images
      using CR enabled immediate, quantitative evaluation of the isocenter.

PMID- 17189933
TI  - [Evaluation of irradiation position in respiratory-gated radiotherapy using a
      phantom system simulating patient respiration].
AB  - Respiratory-gated (RG) radiotherapy is useful for minimizing the irradiated
      volume of normal tissues resulting from the shifting of internal structures
      caused by respiratory movement. The present study was conducted to evaluate the
      treatment field in RG radiotherapy using a phantom system simulating patient
      respiration. A phantom system consisting of a 3-cm ball-shaped dummy tumor and
      film placed in a cork lung phantom was used (THK Co., Ltd.). RG radiotherapy was
      employed in the expiratory phase. The phantom movement distance was set to 2 cm,
      and the gating signals from a respiratory-gating system (AZ-733V, Anzai Medical)
      were varied. The settings used for irradiation were an X-ray energy of 6 MV
      (PRIMUS, Toshiba Medical Systems), treatment field of 5 cm x 7 cm, and X-ray dose
      of 100 MU. Images were acquired using an electric portal-imaging device (EPID,
      OPTIVUE 500), and the X-ray dose distribution was measured by the film method. In
      images acquired using the EPID, the tumor margins became less clear when the
      gating signals were increased, and the ITVs were determined to be 3.6 cm, 3.7 cm,
      4.2 cm, and 5.1 cm at gating rates of 10%, 25%, 50%, and no gate, respectively.
      With regard to the X-ray dose distribution measured by the film method, the dose
      profile in the cephalocaudal direction was shifted toward the expiratory phase,
      and the degree of shift became greater when the gating signals were increased. In
      addition, the optimal treatment fields in the cephalocaudal direction were
      determined to be 5.2 cm, 5.2 cm, 5.6 cm, and 7.0 cm at gating rates of 10%, 25%,
      50%, and no gating, respectively. Although RG radiotherapy is useful for
      improving the accuracy of radiotherapy, the characteristics of the RG
      radiotherapy technique and the radiotherapy system must be clearly understood
      when this method is to be employed in clinical practice. Image-guided
      radiotherapy (IGRT) is now assuming a central role in radiotherapy, and properly
      identifying internal margins is an important issue for ensuring optimal
      treatment. The results of this study confirmed that it is necessary to ensure the
      optimal treatment field in radiotherapy of the trunk and that it is essential to
      confirm tumor position on the basis of image evaluation.

PMID- 17189934
TI  - [Approximation of collimator scatter factor Sc by a saturation model].
AB  - To more easily estimate accurate values of collimator scatter facor, S(c), we
      suggest a two-component saturation model that accounts for scatter from the
      primary collimator and flattening filter and from the collimator jaws. This
      model, which assumes an exponential distribution of scatter intensity, was tested
      by in-air measurements using a mini-phantom for 4 MV and 10 MV X-rays of a Clinac
      2100 C/D linear accelerator. The results showed a good fit of this model to our
      measured data (R(2)>0.9993). When the measured value was divided into the primary
      collimator/flattening filter component and the collimator jaw component, as
      expected, the former component showed a rapid and full saturation curve with
      increased field size, while the latter showed an almost linearly increasing
      curve. Therefore, we think that this saturation model is useful for the
      estimation of S(c) and is applicable to monitor unit calculation for an
      asymmetric field.

PMID- 17189935
TI  - Determination of gate-on and -off timing in respiration-gated radiotherapy.
AB  - The purpose of this study was to develop an efficient method of determining gate
      on and -off timing in respiration-gated radiotherapy. Gate-on and -off timing in
      a breathing cycle were defined as the respiratory signal level for the start of
      irradiation (Ls) in the expiration phase and that for the end of irradiation (Le)
      in the inspiration phase, respectively. Thirty subjects participated in this
      study. The diaphragm was used as the tracking target, and time-dependent changes
      in the position of the target were measured together with those in the
      respiratory signal level. For each subject, the following maps were created by
      varying the combination of Ls and Le: absolute target displacement (ATD) map,
      relative target displacement (RTD) map, and gate-on duty cycle (GDC) map. By
      classifying respiratory signal waveforms, three respiratory types were derived
      (A: the length of end-expiration level >40% of a breathing cycle, B: the length
      of end-expiration level <or=40% and that of end-inspiration level >20% of a
      breathing cycle, and C: the length of end-expiration level <or=40% and that of
      end-inspiration level <or=20% of a breathing cycle). For each respiratory type,
      average RTD and GDC maps were created. We presented an algorithm to obtain the
      optimal Ls and Le using the RTD (or ATD) and GDC maps, and this algorithm was
      verified by demonstrating that, in determining Ls and Le for a subject, the
      average RTD and GDC maps corresponding to the subject's respiratory type could be
      used effectively.

PMID- 17189936
TI  - [Examination of formula for enhanced dynamic wedge factors in symmetric and
      asymmetric fields].
AB  - We proposed a formula for the enhanced dynamic wedge (EDW) factor in the half
      field (HF) that combined the formula proposed by Liu et al. in 1998 and their
      formula in 2003. When the EDW was used for irradiation to the tangent line of the
      HF breast, the values calculated by our formula and the measured values were
      consistent within 0.5%. We showed that our proposed formula was useful, easy to
      use, and more accurate than the conventional formula. The purpose of this study
      was to examine the available range of the wedge factor of symmetrical and
      asymmetric EDW calculated by our formula. As a result of the examination, the
      values calculated by our formula and the measured values were consistent within
      2% except for highly asymmetric EDW. We created a spreadsheet to calculate the
      wedge factor easily and accurately. We will examine the reason why the calculated
      and measured values were greater than 2%, and improve our formula so that it can
      be used in a wider range.

PMID- 17189937
TI  - Examination of beam profile measurement using an imaging plate by the light
      exposure fading method for quality assurance of external radiation therapy.
AB  - High-resolution film dosimetry has been used for several decades to check and to
      measure two-dimensional dose distributions. However, in recent years, the
      automatic processor has been replaced by the spread of computed radiography, or
      has been little used hospitals. In this study, we measured the off-center ratio
      (OCR) of the open field, after an irradiating radiation beam was delivered to the
      imaging plate (IP) under conditions in which the IP was exposed to a fixed amount
      of light with fading, and compared these data with the OCR measured by an
      ionization-chamber dosimeter, which is the standard method used for measuring
      radiation dose. Profile measurement using IP could be achieved by performing
      light fading, even at a range of more than 100 MU. Further, by using a metallic
      filter, we succeeded in demonstrating that the profile measurement of IP in an
      open irradiation field could approximate the values of those obtained by an
      ionization chamber dosimeter. This method can serve as a simple, easy-to-use
      method for evaluating the QA of dose distribution in radiation therapy.

PMID- 17189938
TI  - RNase MRP RNA and human genetic diseases.
AB  - RNase MRP RNA is the RNA subunit of the RNase mitochondrial RNA processing (MRP)
      enzyme complex that is involved in multiple cellular RNA processing events.
      Mutations on RNase MRP RNA gene (RMRP) cause a recessively inherited
      developmental disorder, cartilage-hair hypoplasia (CHH). The relationship of the
      genotype (RMRP mutation), RNA processing deficiency of the RNase MRP complex, and
      the phenotype of CHH and other skeletal dysplasias is yet to be explored.

PMID- 17189939
TI  - Setting the record straight.
AB  - The discovery of serious errors in two recent papers in the journal leads to
      lessons for authors, referees and editors.

PMID- 17189940
TI  - Does the fusiform face area contain subregions highly selective for nonfaces?

PMID- 17189941
TI  - Measuring selectivity in fMRI data.

PMID- 17189943
TI  - Tolerance to opiate reward: role of midbrain IRS2-Akt pathway.

PMID- 17189944
TI  - Hair bundles: keeping it together.

PMID- 17189945
TI  - How dopamine neurons survive.

PMID- 17189946
TI  - Cortico-hippocampal interaction during up-down states and memory consolidation.

PMID- 17189947
TI  - Knowing without doing.

PMID- 17189948
TI  - PARsing the events of myelination.

PMID- 17189949
TI  - Neural recognition molecules of the immunoglobulin superfamily: signaling
      transducers of axon guidance and neuronal migration.
AB  - Recognition molecules of the immunoglobulin superfamily have important roles in
      neuronal interactions during ontogeny, including migration, survival, axon
      guidance and synaptic targeting. Their downstream signal transduction events
      specify whether a cell changes its place of residence or projects axons and
      dendrites to targets in the brain, allowing the construction of a dynamic neural
      network. A wealth of recent discoveries shows that cell adhesion molecules
      interact with attractant and repellent guidance receptors to control growth cone
      and cell motility in a coordinate fashion. We focus on the best-studied
      subclasses, the neural cell adhesion molecule NCAM and the L1 family of adhesion
      molecules, which share important structural and functional features. We have
      chosen these paradigmatic molecules and their interactions with other recognition
      molecules as instructive for elucidating the mechanisms by which other
      recognition molecules may guide cell interactions during development or modify
      their function as a result of injury, learning and memory.

PMID- 17189954
TI  - An analysis of erectile function after intensity modulated radiation therapy for
      localized prostate carcinoma.
AB  - Radiation therapy for prostate cancer can cause erectile dysfunction (ED).
      Intensity Modulated Radiation Therapy (IMRT) can reduce the amount of radiation
      to surrounding tissues associated with ED. We characterize the incidence of and
      factors associated with ED in prostate cancer patients after IMRT at the National
      Naval Medical Center (NNMC). Patients potent by definition of the Sexual Health
      Inventory for Men (SHIM) before treatment completed the specific erectile
      questions of the SHIM after IMRT. Statistical analyses were performed to examine
      the relationships between several factors and ED. Thirty-two of 45 patients with
      mean age of 68.2 years (50-86 years) completed the SHIM. The median follow-up was
      36.8 months (16-63.6 months) as defined by the time from completion of therapy to
      reassessment with the SHIM. Eight of 32 patients (25%) had no post-treatment ED
      (SHIM score 22-25), three of 32 (9%) had mild post-treatment ED (SHIM score 17
      21), five of 32 (16%) had mild to moderate ED (SHIM score 12-16), five of 32
      (16%) had moderate ED (SHIM score 8-11) and 11 of 32 (34%) had severe post
      treatment ED (SHIM score<8). Post-treatment potency was significantly associated
      with the pre-treatment SHIM score (P=0.001) and history of hypertension (P=0.03).
      The mean radiation dose to the penile bulb and volume of penile bulb treated were
      not associated with post-treatment potency (P=0.38, 0.76, respectively). IMRT
      maintains potency in the majority of patients. This analysis compares favorably
      in preserving erectile function to previously reported series using conventional
      external beam radiation therapy techniques. The dose of radiation received by the
      penile bulb and volume of penile bulb were not associated with post-treatment ED
      in this analysis.

PMID- 17189955
TI  - The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in
      men with benign prostatic hyperplasia.
AB  - The dual 5alpha-reductase inhibitor, dutasteride has been shown to suppress serum
      dihydrotestosterone (DHT) by >90%. In the present study, the effect of
      dutasteride 0.5 mg/day on intraprostatic DHT levels was investigated. In this
      multicenter, double-blind trial, 43 men with benign prostatic hyperplasia (BPH)
      scheduled to undergo transurethral resection of the prostate (TURP) were
      randomized to receive dutasteride, 0.5 mg/day or placebo for 3 months before
      surgery. Intraprostatic DHT, testosterone and dutasteride levels were determined
      at the time of TURP. Changes in serum DHT and testosterone from baseline, and
      both serum and intraprostatic dutasteride levels at the time of TURP were also
      assessed. Dutasteride reduced intraprostatic DHT by 94% relative to placebo
      (P<0.001); the adjusted mean intraprostatic DHT concentration was 3.23 and 0.209
      ng/g in the placebo and dutasteride groups, respectively. In the dutasteride
      group, serum DHT was reduced from baseline by 93% at month 3, a significantly
      greater reduction (P<0.001) than the 15% decrease observed in the placebo group.
      There was a reciprocal increase in intraprostatic testosterone but the level of
      intraprostatic testosterone in the dutasteride group tended to be lower than the
      intraprostatic DHT level in the placebo group (P=0.06). Significant
      intraprostatic DHT suppression was achieved in all subjects who received
      dutasteride, regardless of the level of intraprostatic dutasteride. There was a
      strong positive correlation between serum and intraprostatic dutasteride
      concentrations (R(2)=0.73). After 3 months of treatment, dutasteride 0.5 mg/day
      provided near-complete suppression of both intraprostatic and serum DHT in men
      with BPH.

PMID- 17189956
TI  - Visual estimation of the tumor volume in prostate cancer: a useful means for
      predicting biochemical-free survival after radical prostatectomy?
AB  - Absolute and relative (ratio absolute tumor volume to gland volume) tumor volumes
      were visually estimated in 528 prostatectomy specimens. Surveying a mean post
      surgical follow-up of 49 months, both parameters were analyzed regarding their
      aptitude for prognostication. We found relative tumor volumes exceeding 25% to
      independently predict biochemical recurrence reflected by post-surgical prostate
      specific antigen progression, which was also determined to be increased to 28%
      when absolute tumor volumes exceeded 10 cm(3). However, this cutoff failed to be
      an independent prognosticator. Because the visual estimation of both parameters
      can easily be performed, they are felt to be formidable candidates for deriving
      prognostic information during routine procedures.

PMID- 17189957
TI  - Androgen decreases osteoprotegerin expression in prostate cancer cells.
AB  - Osteoprotegerin (OPG), a key regulator of bone resorption, is hypothesized to
      have a role in prostate cancer (CaP) bone metastasis. As advanced CaP is treated
      by androgen ablation, we examined if androgen modulates OPG expression by CaP
      cell lines in vitro. Basal levels of secreted OPG protein were significantly
      greater in androgen-independent PC-3 cells compared with androgen-responsive
      LNCaP-FGC cells (P<0.001); OPG was not detected in the androgen-responsive CaP
      cell lines LAPC-4 or DuCaP. Treatment with 5alpha-dihydrotestosterone (5alpha
      DHT) significantly decreased OPG protein levels in both PC-3 and LNCaP-FGC, with
      maximal suppression using 10(-9)-10(-7) M 5alpha-DHT in PC-3 (P<0.01; day 3), and
      using 10(-10)-10(-9) M 5alpha-DHT in LNCaP-FGC cells (P<0.01; day 6). OPG
      messenger RNA levels were not significantly altered by this 5alpha-DHT treatment.
      Co-treatment with 10(-6) M flutamide blocked 5alpha-DHT inhibition of OPG protein
      expression in LNCaP-FGC cells. These data suggest that androgen may modulate OPG
      protein levels in CaP cell lines in vitro using a post-transcriptional mechanism.

PMID- 17189958
TI  - A proteomic study of serum from children with autism showing differential
      expression of apolipoproteins and complement proteins.
AB  - Modern methods that use systematic, quantitative and unbiased approaches are
      making it possible to discover proteins altered by a disease. To identify
      proteins that might be differentially expressed in autism, serum proteins from
      blood were subjected to trypsin digestion followed by liquid chromatography
      electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF)
      instruments to identify differentially expressed peptides. Children with autism 4
      6 years of age (n=69) were compared to typically developing children (n=35) with
      similar age and gender distributions. A total of 6348 peptide components were
      quantified. Of these, five peptide components corresponding to four known
      proteins had an effect size >0.99 with a P<0.05 and a Mascot identification score
      of 30 or greater for autism compared to controls. The four proteins were:
      Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1),
      Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were
      higher in children with high compared to low functioning autism. Apos are
      involved in the transport of lipids, cholesterol and vitamin E. The complement
      system is involved in the lysis and removal of infectious organisms in blood, and
      may be involved in cellular apoptosis in brain. Despite limitations of the study,
      including the low fold changes and variable detection rates for the peptide
      components, the data support possible differences of circulating proteins in
      autism, and should help stimulate the continued search for causes and treatments
      of autism by examining peripheral blood.

PMID- 17189959
TI  - Involvement of cannabinoid CB2 receptor in alcohol preference in mice and
      alcoholism in humans.
AB  - We tested if cannabinoid type 2 receptor (CB2) in the central nervous system
      plays a role in alcohol abuse/dependence in animal model and then examined an
      association between the CB2 gene polymorphism and alcoholism in human. Mice
      experiencing more alcohol preference by drinking showed reduced Cb2 gene
      expression, whereas mice with little preference showed no changes of it in
      ventral midbrain. Alcohol preference in conjunction with chronic mild stress were
      enhanced in mice treated with CB2 agonist JWH015 when subjected to chronic
      stress, whereas antagonist AM630 prevented development of alcohol preference.
      There is an association between the Q63R polymorphism of the CB2 gene and
      alcoholism in a Japanese population (P=0.007; odds ratio 1.25, 95% CI, (1.06
      1.47)). CB2 under such environment is associated with the physiologic effects of
      alcohol and CB2 antagonists may have potential as therapies for alcoholism.

PMID- 17189960
TI  - Molecular therapy in the microRNA era.
AB  - MicroRNAs (miRNAs) consist of a growing class of non-coding RNAs (ncRNAs) that
      negatively regulate the expression of genes involved in development,
      differentiation, proliferation, apoptosis and other important cellular processes.
      miRNAs are usually 18-25 nt long and are each able to regulate several mRNAs by
      mechanisms such as incomplete base pairing and Post-Transcriptional Gene
      Silencing (PTGS). A growing number of reports have shown that aberrant miRNA
      expression is a common feature of human diseases including cancer, which has
      sparked interest in targeting these regulators of gene expression as a means of
      ameliorating these diseases. Here, we review important aspects of miRNA function
      in normal and pathological states and discuss new modalities of epigenetic
      intervention strategies that could be used to amend defects in miRNA/mRNA
      interactions.

PMID- 17189961
TI  - Diuretic-gene interaction and the risk of myocardial infarction and stroke.
AB  - This study investigates whether the interaction between diuretics and alpha
      adducin (ADD1) G460W or G-protein beta3-subunit (GNB3) rs2301339 polymorphism
      modifies the risk of myocardial infarction (MI) or stroke. Data were used from
      the Rotterdam Study. The drug-gene interaction was determined with a Cox
      proportional hazard model with adjustment for each drug class as time-dependent
      covariates. The risk of MI in current users of low-ceiling diuretics with one or
      two copies of the ADD1 W-allele (hazard ration (HR)=0.92) was similar compared to
      the expected joint effect of the W-allele and low-ceiling diuretics on a
      multiplicative scale (1.04 x 0.90=0.94) (synergy index (SI):0.99; 95% confidence
      interval (CI): 0.43-2.27). No drug-gene interaction was found on the risk of
      stroke (SI:0.66; 95% CI:0.43-1.27). In addition, a trend towards an interaction
      was found between current use and the GNB3 rs230119 G/A polymorphism on the risk
      of MI (SI: 0.51; 95% CI: 0.23-1.15), whereas no interaction on the risk of stroke
      was found (SI: 0.84; 95% CI: 0.46-1.56).

PMID- 17189963
TI  - Dengue & dengue hemorrhagic fever.

PMID- 17189964
TI  - Etiological pattern of blepharoptosis among patients presenting in teaching
      hospital.
AB  - The purpose of this study was to find out the etiological pattern of
      blepharoptosis among patients presenting in BPKLCOS, T.U. Teaching Hospital. This
      was a hospital based descriptive and cross-sectional study conducted from
      February 2003 to July 2004. A total of 125 patients with ptosis were evaluated.
      78 cases (62.4%) were congenital and 47 cases (37.6 %) were acquired. Congenital
      simple ptosis and congenital complicated ptosis comprised of 58% and 42%
      respectively. Among the acquired cause, ptosis due to trauma was the commonest
      32%, followed by third cranial nerve palsy 25.5%, myasthenia gravis 17%,
      aponeurotic 10.7%, chronic progressive external ophthalmoplegia 8.5% etc.
      Aetiology-wise, myogenic ptosis was the commonest (65.6%) which was followed by
      neurogenic (16.8%), traumatic (12%) and aponeurotic ptosis (5.6%). Congenital
      ptosis is more common than acquired ptosis. Myogenic ptosis is the most
      predominant type of ptosis. Among the congenital ptosis, congenital simple ptosis
      is more common than congenital complicated ptosis. Among the acquired cases
      trauma, third cranial nerve palsy and myasthenia gravis are the major attendees.

PMID- 17189962
TI  - The DRD2 TaqI-B polymorphism and its relationship to smoking abstinence and
      withdrawal symptoms.
AB  - The dopamine receptor D2 (DRD2) gene has polymorphisms that have been linked to
      regulation of the dopamine system and to an increased prevalence of smoking. The
      present study examined the relationship of the DRD2 TaqI-A and -B polymorphisms
      with short-term clinical outcome (abstinence and withdrawal symptoms), collected
      from daily (14 pre-quit and 42 post-quit) diary data among smokers (n=116)
      treated with the nicotine patch plus either venlafaxine or placebo. The results
      showed that B1/B1 or B1/B2 smokers were slightly less likely to be abstinent on a
      given day than those homozygous for the TaqI-B2 allele. Significant DRD2 TaqI-B x
      time interactions were found for several of the withdrawal scales, indicating
      that those smokers with the B1/B1 or B1/B2 genotypes tended to report more
      symptoms over time compared to those with the B2/B2 genotype. No interactions or
      main effects were found for the DRD2 TaqI-A polymorphism. The findings
      demonstrate that smokers homozygous for the TaqI-B2 allele experience progressive
      improvement in self-reported withdrawal symptoms while smokers with the TaqI-B1
      allele showing little change.

PMID- 17189965
TI  - Reduction of acute anterior shoulder dislocations: comparing intraarticular
      lignocaine with intravenous anesthesia.
AB  - Anterior shoulder dislocation is the most common dislocation in the body. Various
      methods of anesthesia are available for reduction. The objective of this study
      was to compare the application of intra-articular anesthesia with intravenous
      anesthesia for reduction of acute anterior shoulder dislocation. This study was
      conducted at Kathmandu Medical College Teaching Hospital (KMCTH) and Kathmandu
      Hospital and comprised of patients coming with anterior dislocation of shoulder
      from July 2001 to June 2005. Forty-five patients aged 17-55 years with no
      associated fractures of adjoining bones were included in the study. In twenty
      three patients, reduction was done using intra-articular anesthesia and in 22
      patients intravenous anesthesia was given. In five patients (three in intra
      articular group and two in intravenous group) the reduction technique had to be
      changed to the Hippocratic method. In these three patients intravenous anesthesia
      had to be given after intra-articular anesthesia failed to relieve pain and
      spasm. In the intravenous group two patients had to be admitted overnight while
      in the intra-articular group none had to be admitted to the hospital. However, in
      the intra-articular group the average time taken from injection to reduction was
      significantly longer (<.001). The use of intra-articular lignocaine for reduction
      of shoulder dislocation is safe and effective especially when patients present
      early. In patients presenting late (more than 5 hours) intravenous anesthesia
      should be primarily considered as the method for shoulder reduction.

PMID- 17189966
TI  - Patterns of organophosphorous poisoning attending a teaching hospital.
AB  - The objective of this was to study the pattern of patients of organophosphorous
      (OP) poisoning attending Kathmandu Medical College Teaching Hospital (KMCTH).
      This is a retrospective study of OP poisoning from hospital records were analyzed
      meticulously and data extracted. Data collected were: patient's demographics,
      motive for poisoning, type of OP poison, arrival time, time since ingestion,
      patient's vitals, predisposing factors, serum cholinesterase levels, treatment
      given, duration of hospital stay and mortality. A total of 47 patients of OP
      poisoning attended KMCTH from Aug 2003 to July 2005. 22(46.8%) cases were male
      and 25(53.2%) were female. The maximum number of patients were between the age of
      20-40 (33-70.2%). Married patients outnumbered the unmarried (35/74.5% vs
      12/25.5%). The most common motive for poisoning was suicidal, 41 cases (87.2%).
      Metacid (methyl-parathion) was the most commonly used OP compounds in 32 (68%)
      patients. Interpersonal marital relationship seemed to be the commonest
      predisposing factor, 23 cases (48.9%). The commonest time of presentation was
      between 6 pm-12 midnight. 7(57.4%) cases presented within 2 hours of ingestion of
      the poison. Serum cholinesterase level measured after full atropinisation was
      >50% of normal level in 17 cases (36.2%). 10 cases (21.3%) required respiratory
      support. Intermediate syndrome (IMS) was observed in 3 cases. Overall mortality
      occurred in 3 cases (6.4%). This study highlights the problem of OP poisoning in
      our region. Establishment of strict policies against the sale and availability of
      insecticides and pesticides which are freely available in the market is an
      effective way to control OP poisoning.

PMID- 17189967
TI  - Study of accuracy of commonly used fetal parameters for estimation of gestational
      age.
AB  - Estimation of the gestational age by sonographic measurements of fetal parameters
      is usually done by measuring mean sac diameter (MSD), Crown-rump length (CRL),
      biparietal diameter (BPD), head circumference (HC), femoral length (FL) and
      abdominal circumference (AC) depending on the trimester of pregnancy. This is a
      prospective study to see the correlation of different fetal parameters in
      estimating the gestational age. A total of 71 normal women were taken and
      ultrasonogram was done to take MSD and CRL in 1st trimester and BPD, HC, FL and
      AC in 2nd and 3rd trimester. Gestational age was calculated by MSD using Rempen
      normogram and Hadlock normograms were used for the rest of fetal parameters.
      Gestational age by LMP was also calculated at the same time. Correlation of
      different fetal parameters in estimating gestational age in different trimesters
      was done by Pearson correlation. Pearson correlation showed that the CRL was the
      best fetal parameter (correlation coefficient of 0.909) in the first trimester.
      The correlation of MSD and average gestational age by MSD and CRL was with
      correlation coefficients of 0.778 and 0.888 respectively. Thus the averaging of
      gestational age in 1st trimester decreases the accuracy in the gestational age
      estimation. Correlation of gestational age by BPD, HC, FL and AC and their
      average in 2nd trimester showed that the best correlation was by AC and the least
      correlation by BPD in this study. It is in contrary to other studies which could
      be due to chance finding or bias because of prospective study. Pearson
      correlation calculated in 3rd trimester showed HC and FL were better parameters
      than BPD and AC. Average gestational age by simple averaging of BPD, HC, FL and
      AC gives more accurate estimation of gestational age in both 2nd and 3rd
      trimester.

PMID- 17189968
TI  - An epidemiological study of road traffic accident cases attending emergency
      department of teaching hospital.
AB  - Several studies have shown that road traffic injuries are a major cause of death
      and disability globally, with a disproportionate number occurring in developing
      countries. The growth in numbers of motor vehicles is a major contributing factor
      in the rising toll of fatalities and injuries from road traffic crashes in poor
      countries. In this study, we reviewed medical records of all the victims of road
      traffic accidents attending the emergency department of Kathmandu Medical College
      Teaching Hospital within a year. A total of 757 road traffic victims were
      reported which accounted for 6.66% of all the cases attending the emergency.
      49.93% cases belonged to 21-40 years age group. The most common victim group
      comprised the pedestrians (56.54%) with motorcycle (55.09%) being the most
      commonly involved vehicle. 44.65% accidents occurred in evening (12-6 pm). The
      lower limbs (in 42.0% cases) were the most common body region injured with
      superficial injuries (bruise/abrasion) accounting for the most common injury
      pattern followed by soft tissue injuries, incised/lacerated wounds and fractures
      and dislocations. Most accidents occurred in the April-June trimester.

PMID- 17189969
TI  - Association of systemic diseases with retinal vein occlusive disease.
AB  - Retinal vein occlusion (RVO) is the second commonest vascular disease of the eye,
      second only to Diabetic Retinopathy. The association of the retinal vein
      occlusion with other systemic disease likes hypertension, diabetes mellitus and
      others has been well documented. With the increase in persons being affected from
      these disorders, patients with retinal vein obstruction are also increasing.
      Hence, a study was designed to evaluate all cases of RVO to find out its
      association with systemic disorders. A total of 100 patients (106 eyes) were
      enrolled in the study. Out of which, 66 cases reported to have Brach Retinal Vein
      Occlusion (BRVO) and rest 34 cases with Central Retinal Vein Occlusion (CRVO).
      Among the associated systemic diseases, hypertension and diabetes mellitus
      accounted for 84% cases. Isolated hypertension (54%) was most commonly seen
      followed by diabetes mellitus (8%). The prevalence of BRVO was almost twice as
      compared to CRVO. The high association of various systemic disorder especially
      Hypertension and diabetes further supports the need of early and periodic eye
      examination for those suffering from these disorders.

PMID- 17189970
TI  - Foreign body in the rectosigmoid colon.
AB  - A 55 years old male presented with history of assault and insertion of a "glass
      object" through his anus. Examination and investigation of the patient revealed a
      bottle in the rectosigmoid colon. The bottle was manipulated and delivered out
      transanally under general anesthesia.

PMID- 17189971
TI  - Curative interstitial brachytherapy for early stage carcinoma lip.
AB  - Brachytherapy is potentially useful in the treatment of head-and-neck cancers,
      because most tumor sites, such as the lip, tongue, floor of mouth, tonsil,
      pharynx, nasopharynx, sinuses, and neck, are accessible for the placement of
      afterloading applicators and catheters. It has the advantage of delivering a
      higher radiation dose to the tumor while sparing surrounding normal tissue from
      radiation. Furthermore, the overall treatment duration is shorter, and the dose
      distribution confirms to tumor shape. Brachytherapy is used as "monotherapy" for
      the treatment of small primary tumors or recurrent disease after external beam
      radiation therapy (EBRT). Small cancers of the lip (less than 2 cm) are treated
      equally well with surgery or radiation therapy with excellent cosmetic and
      functional results seen in radiation therapy. We treated an 18-year old male
      diagnosed as stage I carcinoma lip with curative interstitial brachytherapy. He
      was treated to a dose of 3 Gy per fraction, two fractions per day at interval of
      6 hours between the two fractions for 6 days. He therefore received a total dose
      of 36 Gy with High Dose Rate (HDR) Brachytherapy, which is equivalent to 58.36 Gy
      conventional radiotherapy dose. At two months follow, the patient is clinically
      disease free and has no complaints.

PMID- 17189973
TI  - Involvement of STAT3 in bladder smooth muscle hypertrophy following bladder
      outlet obstruction.
AB  - We examined the involvement of the signal transducer and activator of
      transcription 3 (STAT3) in bladder outlet obstruction (BOO)-induced bladder
      smooth muscle hypertrophy using a rat in vivo and in vitro study. BOO induced
      increases in bladder weight and bladder smooth muscle thickness 1 week after the
      operation. By using antibody microarrays, 64 of 389 proteins blotted on the array
      met our selection criteria of an INR value between > or = 2.0 and < or = 0.5.
      This result revealed up-regulation of transcription factors, cell cycle
      regulatory proteins, apoptosis-associated proteins and so on. On the other hand,
      down-regulation (INR value < or = 0.5) of proteins was not found. In a profiling
      study, we found an increase in the expression of STAT3. A significant increase in
      nuclear phosphorylated STAT3 expression was confirmed in bladder smooth muscle
      tissue by immunohistochemistry and Western blot analysis. Cyclical stretch
      relaxation (1 Hz) at 120% elongation significantly increased the expression of
      STAT3 and of alpha-smooth muscle actin in primary cultured bladder smooth muscle
      cells. Furthermore, the blockade of STAT3 expression by the transfection of STAT3
      small interfering RNA (siRNA) significantly prevented the stretch-induced
      increase in alpha-smooth muscle actin expression. These results suggest that
      STAT3 has an important role in the induction of bladder smooth muscle
      hypertrophy.

PMID- 17189972
TI  - Saphenous--peritoneal shunt in refractory ascites: a neglected technique.
AB  - Management of intractable ascites has always been a challenge. Peritoneovenous
      shunt (PVS) plays a major role in the surgery of intractable ascites in patients
      with liver cirrhosis. Positive pressure gradient between the ascitic fluid and
      venous pressure leading to one-way drainage of ascitic fluid into venous
      circulation is the mainstay. Over decades, various modifications of shunting
      technique have been done. Here we report our experience with this procedure which
      is safe, easy and effective. Here the long saphenous vein is used as a drainage
      system. One-way ascites flow is ensured by a natural valve in the saphenous
      orifice.

PMID- 17189974
TI  - Assessment of head wear more than ten years after total hip arthroplasty: 22-mm
      zirconia vs. metal heads.
AB  - The present retrospective study assessed radiographs to determine socket wear in
      total hip arthroplasty (THA) with 22-mm zirconia or COP (Cobalt-Chrome alloy rich
      in Cobalt and Phosphorous) heads, and in cemented stems at more than 10 years
      after operation. Sockets of ultra high molecular weight polyethylene were used in
      each of two THA groups (13 hips each) in a clinical trial in our hospital between
      1989 and 1990. Three observers carried out masked assessments of the radiographs.
      Upon final examination, there was no remarkable loosening in the zirconia or COP
      group, and no case had required revision surgery as of 2005. There was a
      statistically significant difference between the 2 groups in average annual
      linear wear, at 0.093 mm/year and 0.046 mm/year in the zirconia and COP groups,
      respectively. Volume wear and average annual volume wear were also significantly
      greater in the zirconia group despite its superior mechanical strength and
      toughness in vitro. Our present findings do not confirm early expectations of
      lower wear in long-term results of 22-mm zirconia femoral heads used in THA.

PMID- 17189975
TI  - Unilateral ibotenic acid lesions of the prefrontal cortex reduce rotational
      behavior in 6-hydroxydopamine-lesioned rats.
AB  - Rats with 6-hydroxydopamine (6-OHDA)-induced lesions of the substantia nigra are
      used as a model of Parkinson.s disease (PD), and these "lesioned" rats exhibit a
      rotational behavior when further injected with apomorphine (APO). We examined
      whether lesions in the prefrontal cortex (PFC) could modify the rotational
      behavior in PD model rats. Rats initially received unilateral lesions of the
      substantia nigra by 6-OHDA injection, and then their rotational behavior was
      measured. Two PFC lesions were achieved by intracerebral infusions of ibotenic
      acid, followed by measurement of APO-induced rotation. Rotation was reduced by
      approximately 30% after PFC injury. The PFC may have functional influence on the
      basal ganglia and may be involved in the pathophysiology of the rotational
      behavior of PD model rats.

PMID- 17189976
TI  - Study of interleukin-6 in the spread of colorectal cancer: the diagnostic
      significance of IL-6.
AB  - We investigated the diagnostic significance of IL-6 for lymph node metastasis
      and/or hepatic metastasis from colorectal cancer in 65 patients and evaluated the
      contributions of 8 factors (IL-6, HGF, IL-1beta, TNF-alpha, TGF-beta1, ELAM-1,
      ICAM-1, VCAM-1) toward Dukes.s classification of 53 patients. We also examined IL
      6 expression in tumor tissue. From the receiver operating characteristic (ROC)
      curve analysis, an optimal cutoff value of 5.8 pg/ml was determined to classify
      lymph node and/or hepatic metastasis, and that of 6.3 pg/ml was determined to
      classify hepatic metastasis. These values indicated sensitivities of 55.0% and
      71.4%, and specifi cities of 100% and 88.6%, respectively. IL-6, HGF, and ELAM-1
      were very useful for distinguishing among Dukes.s A/B group, C group, and D
      group. In all cases with high IL-6 values (more than 25.0 pg/ml),
      immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer
      cells. IL-6 is strongly suspected to be involved in lymph node and/or hepatic
      metastasis by promoting it through HGF, and serum IL-6 value (pg/ml) would be
      useful diagnostically to estimate whether or not there is a high risk of lymph
      node and/or hepatic metastasis.

PMID- 17189978
TI  - Three type 6 hepatitis C virus subgroups among blood donors in the Yangon area of
      Myanmar are identified as subtypes 6m and 6n, and a novel subtype by sequence
      analysis of the core region.
AB  - Previously, using phylogenetic analysis of NS5b sequences, we found that three
      type 6 variant subgroups (M6-1, M6-2 and M6-3) exist in Myanmar. According to the
      new nomenclature of hepatitis C, M6-1 and M6-2 belong to subtypes 6m and 6n,
      respectively, but M6-3 is unassigned. In this study, we sequenced and
      phylogenetically analyzed the core region of these type 6 variant subgroups.
      Serum samples assigned as 6m or 6n by NS5b sequence were also identified as 6 m
      or 6n by core region analysis. The M6-3 (sample name MYAN-3E-3) remained
      unassigned to a subgroup based on its core region analysis. The findings of this
      study suggest that either the core region or the NS5b region can be analyzed for
      HCV subtype classification.

PMID- 17189977
TI  - Equation for calculating the concentration of solvent in air that discriminates
      between exposure and non-exposure based on biomarker concentrations in the urine
      of workers.
AB  - To develop a new method for evaluating the intensity of workers. exposures to
      toluene alone or toluene in mixed solvents, regression equations were calculated
      between the concentrations of toluene to which workers were exposed and the
      concentrations of hippuric acid or toluene in workers. urine samples taken at the
      end of their shifts. Thereafter, the discriminant exposure concentration of the
      solvents in air, which was the concentration considered to discriminate exposure
      from non-exposure within a fixed level of error using fiducial ranges of
      individual specimens (DEC-I) or using confidence ranges of regression equation
      (DEC-R), was measured by a scale. The devised equations were applied to calculate
      DEC-I or DEC-R accurately using the formulas expressing a regression line and its
      fiducial ranges or confidence ranges. The equations can calculate not only more
      precise values of DEC-I or DEC-R than can be measured by a scale, but can also
      calculate values corresponding to any level of error. Moreover, DEC-I and DEC-R
      can be defined by the equations. The concentration capable of discriminating TLV
      (threshold limit value) exposure from non-TLV exposure was estimated using
      fiducial ranges (DTL-I) and then using confidence ranges of the regression
      equation (DTL-R).

PMID- 17189979
TI  - Detection of fibronectin-binding proteins in Clostridium perfringens.
AB  - Clostridium perfringens is an anaerobic spore-forming pathogen of humans and
      animals. C. perfringens type A strains, 13, CPN50, and NCTC8237, isolated from
      human gas gangrene, bound specifically to human fi bronectin (Fn). The trypsin
      treatment of the bacterial cells significantly reduced the Fn-binding. A ligand
      blotting analysis of all three C. perfringens strains revealed that 5 protein
      bands of 34 kDa, 29 kDa, 26 kDa, 17 kDa, and 12 kDa specifically bound to
      biotinylated Fn. These results suggest that C. perfringens possesses certain Fn
      binding proteins on the cell surface.

PMID- 17189980
TI  - Massive intravascular hemolysis in a patient infected by a Clostridium
      perfringens.
AB  - Clostridium perfringens infection is a very rare cause of massive intravascular
      hemolysis, but it should always be kept in mind, since only early treatment can
      rescue patients from an otherwise rapidly fatal outcome. We report a case of a 78
      year-old diabetic male who was admitted complaining of general fatigue, dark red
      urine, and vomiting. His blood revealed massive hemolysis. Computer tomography
      demonstrated huge liver abscess in the right lobe of the liver. About 1 h after
      admission, he suddenly fell into a critical condition. He died 3 h after
      admission in spite of intensive care and resuscitation. Clostridium perfringens
      was detected from the blood taken before death and from liver abscess by biopsy
      after death. We concluded that this patient died of acute massive intravascular
      hemolysis in septicemia caused by Clostridium perfringens infection.

PMID- 17189982
TI  - Periacinar Clefting and p63 Immunostaining in Prostatic Intraepithelial Neoplasia
      and Prostatic Carcinoma.
AB  - The aim of the present study was to correlate the presence and extent of
      retraction clefting and the expression of p63 in neoplastic glands and glands
      with prostatic intraepithelial neoplasia (PIN) in needle core biopsies. We
      analyzed needle core biopsies from 28 patients with PIN and 41 patients with
      adenocarcinoma. Neoplastic glands and those with PIN were analyzed on high power
      field (400x) and classified in three groups according to the extent of clefting.
      Immunohistochemical staining was performed following Microwave Streptavidin
      ImmunoPeroxidase (MSIP) protocol on DAKO TechMate Horizon automated
      immunostainer. Periacinar retraction clefting was significantly more prominent in
      prostatic carcinoma compared to PIN (p<0.0001) and nonneoplastic glands
      (p<0.0001). There was no difference between normal glands and PIN regarding
      clefting (p=0.8064). p63 was positive around the whole circumference in 12 out of
      28 cases with PIN, and discontinuously positive in remaining 16 PIN cases
      suggesting initial disruption of the basal cell layer. p63 immunostaining was
      also positive in all nonneoplastic glands, and negative in all carcinomas. We
      conclude that retraction clefting was associated with cancer and lack of basal
      cells, but not with PIN. The relationship between clefting and p63 immunostaining
      in prostatic cancer should be further analyzed.

PMID- 17189983
TI  - Clinical findings and HER-2/neu gene amplification status of breast carcinoma
      patients.
AB  - The study group was derived from the archival materials of 48 invasive
      intraductal breast cancer patients who had undergone partial mastectomy/ axillary
      dissection. All patients included in the study had clinically T1-2N0M0 invasive
      ductal carcinoma. To detect HER-2/neu status, fluorescent in situ hybridization
      was performed using a HER-2/neu locus-specific probe. Signals were counted and
      patients were classified in three groups according to signal ratios: signal ratio
      <2, group 1 (n=31); signal ratio 2-4, group 2 (n=11); signal ratio >4, group 3
      (n=6). Ratios of axillary metastatic lymph nodes to dissected total lymph nodes
      were 17%, 23% and 83% in groups 1, 2 and 3 respectively (P=0.003). The number of
      metastatic axillary lymph nodes, and the ratio of microscopic metastatic lymph
      nodes were highest in group 3 (P=0.001 and P=0.008, respectively). No significant
      difference was observed between groups for distant metastasis in a 5-year follow
      up period. Signal ratios decreased with estrogen receptor expression (P=0.03).
      Histopathologically, an irregular growth pattern of the tumor was observed in
      100% of the patients in group 3, and in 54% and 60% in groups 1 and 2,
      respectively (P=0.04). Lymphovascular invasion of the tumor was significantly
      higher in group 3 compared to the other two groups (P=0.01). The extensive
      intraductal component ratio was the highest in group 3 (P=0.04). The appearance
      of desmoplastic reaction and lymphocyte infiltration did not show significant
      difference between the groups. Our results show that HER-2/neu signal ratio
      increases with lymphovascular invasion, an extensive intraductal component,
      irregular growth pattern and axillary metastasis in clinically T1-2N0M0 invasive
      ductal carcinoma of the breast.

PMID- 17189984
TI  - Divergences in diagnosing nodular breast lesions of noncarcinomatous nature.
AB  - Nodular breast lesions of noncarcinomatous origin are often of fibroepithelial
      origin. They may cause classification problems when they are hypocellular or
      hypercellular; the latter setting may also raise the differential diagnosis of
      phyllodes tumors. Thirty equivocal nodular breast lesions were collected and one
      hematoxylin and eosin slide from each was assessed by six pathologists with
      special interest in breast pathology. The overall reproducibility of classifying
      these lesions into categories of fibroadenoma, phyllodes tumor or anything else
      was moderate (kappa value: 0.48). The lack of a uniform nomenclature was not felt
      disturbing for hypocellular lesions, but the discordant diagnosis of tumors
      resembling or representing phyllodes tumors was acknowledged to require
      intervention, such as more obvious implication of guidelines and quality
      assurance programs aiming at assessing diagnoses and prognostic parameters.

PMID- 17189981
TI  - Detection of HER-2/neu gene amplification in breast carcinomas using quantitative
      real-time PCR - a comparison with immunohistochemical and FISH results.
AB  - The aim of our study was to evaluate the value of quantitative real-time-PCR
      (qPCR) in the determination of HER-2/neu amplification status of human breast
      carcinomas by comparing qPCR, FISH and immunohistochemistry results from the same
      samples. A total of 210 breast carcinomas were examined. Ready-to-use CB11
      antibody was applied to detect HER-2/neu oncoprotein expression. In 76 out of 210
      cases FISH was performed, and 162 cases were investigated with qPCR. Seventy-five
      tumors were 2+ or 3+ positive with immunohistochemistry, while 135 samples were
      either completely negative or 1+. In 45 cases results from all three methods were
      available. Out of these, in twenty negative and sixteen positive cases both FISH
      and qPCR led to similar results. The mean qPCR amplification ratio in the
      concordant positive cases was 5.424 while in the qPCR+/FISH- group the mean ratio
      was 2.765. Out of 121 samples with scores of 0 or 1+ immunohistochemical result,
      analyzed also with qPCR, 26 showed HER-2/neu gene amplification. In these cases
      the mean amplification ratio was 2.53. Comparison of FISH and qPCR together with
      immunohistochemistry shows that qPCR is more sensitive to detect HER-2/neu gene
      amplification in tumors scored as 2+ with immunohistochemistry, but the
      diagnostic cut-off ratio should be defined above 2.7 to avoid high number of
      false positive cases. Amongst the immunohistochemistry score 2+ cases, 10 of 18
      showed gene amplification by qPCR while 10 of 26 by FISH. In conclusion, a well
      calibrated HER-2/neu qPCR assay may serve as useful alternative to FISH in breast
      cancer patients.

PMID- 17189986
TI  - Two germline alterations in mismatch repair genes found in a HNPCC patient with
      poor family history.
AB  - The Bethesda guidelines may offer more useful criteria in patients' selection for
      germline mismatch repair gene mutation analysis than guidelines merely based on
      family background. An early onset double primary colorectal cancer patient with
      poor family history with MSI-H status was investigated for MLH1 promoter
      methylation, expression of the MLH1 and MSH2 gene by immunohistochemistry and
      mutations in the MLH1 and MSH2 genes. The index patient carried two germline
      alterations, the p.Val716Met in MLH1 and the c.2210+1G>C in MSH2 genes, and both
      tumors failed to express MLH1 and MSH2 proteins. After subsequent analysis of the
      whole family of the index patient, the p.Val716Met variant can be defined as a
      rare polymorphism with the possible contribution of pathogenicity to tumor
      formation and c.2210+1G>C as a true pathogenic mutation causing an out-of-frame
      deletion of exon 13.

PMID- 17189985
TI  - Estrogen receptor alpha-negative and progesterone receptor-positive breast
      cancer: lab error or real entity?
AB  - Aretrospective study comparing the estrogen receptor (ER) alpha subtype and
      progesterone receptor (PR) profile of breast carcinomas amongst 1625 cases over
      2.5 years was carried out. Strictly speaking it is generally believed that breast
      carcinomas can biochemically express PR only if they are ER-positive. However, a
      few ERalpha-PR+ cases do exist paradoxically. This class of tumors was the focus
      of our study in which we looked at the possible reasons for such an
      immunophenotype and compared it with a group of ERalpha+PR+ breast carcinomas. An
      internationally recognized immunohistochemical method employing monoclonal
      antibodies against estrogen and progesterone receptors was used. Correlations
      with established risk factors i.e. menopausal status, grade, tumor size and lymph
      node status were analyzed for our study group (ERalpha-PR+) and compared with a
      control (ERalpha+PR+). Out of the total 1625 cases, 29.91% (486) were
      ERalpha+PR+, 5.11% (83) were ERalpha+PR-, 56.86% (924) were ERalpha-PR- and 8.12%
      (132) were ERalpha-PR+. Patients' age was significantly lower in the ERalpha-PR+
      group (P=0.002). Statistical analysis of the grading between the two study groups
      revealed no significant difference (P=0.091), although the ERalpha-PR+ group
      contained significantly more poorly differentiated tumors than the ERalpha+PR+
      one (P=0.032). Tumor size was also significantly larger in the ERalpha-PR+ than
      in the ERalpha+PR+ group (P=0.046). The frequency of lymph node metastases was
      independent of receptor profile. In conclusion, our study group does exhibit
      characteristics which are suggestive of a distinct breast cancer phenotype
      (ERalpha-PR+) with a different etiology and prognosis.

PMID- 17189987
TI  - Lithium suppresses epidermal SERCA2 and PMR1 levels in the rat.
AB  - Autosomal dominant mutations in the genes encoding the calcium ATPases SERCA2 and
      PMRI/SPCA1 cause the genodermatoses Darier disease (DD) and Hailey-Hailey disease
      (HHD), respectively. Recent observations indicated that the level of the
      pathogenic proteins greatly decreases in the affected areas of the epidermis in
      these disorders. Here we addressed how lithium, a recognized exacerbating factor
      in Darier disease, affects the epidermal expression of SERCA2 and PMR1/SPCA1 in
      the rat as a model. Standard histologic and immunohistochemical methods were
      utilized in 3 lithium-treated and 3 control animals. A significant suppression of
      epidermal SERCA2 and PMR1 levels were observed as a result of lithium therapy in
      addition to marked qualitative and quantitative changes in the stratum corneum
      and the granular layer of the epidermis in the treated animals. Our findings
      suggest that exacerbating factors in calcium ATPase disorders of the skin
      suppress epidermal SERCA2 and PMR1 levels, further decreasing the already
      haploinsufficient protein expression to a potentially critical level in Darier
      disease and Hailey-Hailey disease, respectively. Lithium therapy should
      specifically be avoided not only in Darier disease, but Hailey-Hailey disease as
      well.

PMID- 17189989
TI  - Protocol modifications influence the result of EGF receptor immunodetection by
      EGFR pharmDx in paraffin-embedded cancer tissues.
AB  - EGF receptor (EGFR) became a useful target for several recently introduced
      therapies of various cancer types including colorectal, lung, head and neck
      cancers and glioblastoma. The successful clinical application of these novel
      molecularly targeted therapies requires the expression of their target, EGFR,
      determined by nucleic acid based or immunohistochemical techniques. However,
      until now, immunohistochemistry has not become a reliable diagnostic approach for
      this purpose. The golden standard for the determination of EGFR protein
      expression in paraffin-embedded cancer tissues is the EGFR pharmDxTM kit. Here we
      show that the recommended protocol may not be optimal for EGFR immunodetection.
      Microwave antigen retrieval and extended primary antibody incubation time
      converted four out of eight EGFR-negative tumors into EGFR-positive in a study of
      50 lung adenocarcinoma cases. Accordingly, we recommend retesting cases negative
      for EGFR with EGFR pharmDxTM using protocol modifications optimizing antigen
      retrieval and the incubation periods.

PMID- 17189988
TI  - Significance of oral Candida infections in children with cancer.
AB  - Candidiasis is common in children with cancer, particularly during periods of
      severe immunosuppression and neutropenia. Our aim was to study the
      microbiological changes in the oral cavity of children with newly diagnosed
      cancer. The study group consisted of 30 consecutive children and adolescents, 16
      with acute lymphoblastic leukemia and 14 with solid tumors. Oral cultures to
      detect fungi and bacteria were conducted for all patients before treatment,
      during and after neutropenic episodes. In 23 patients developing fever
      simultaneous throat, urine and blood sampling was carried out. No pathogens were
      found in the cultures taken before the outset (30 cultures) or after recovery
      from (30 cultures) the neutropenic episodes. In the 45 oral cultures taken during
      the neutropenic episodes 38 (84.4%) proved positive. Fungi were the most
      frequently isolated oral pathogens: 33/38 yeast and 6/38 bacterial infections
      were identified. There was no association between the underlying malignancy and
      the occurrence of the positive cultures. Of the 30 patients, all 23 (76.7%) who
      have developed moderate-to-severe neutropenia, developed oral fungal colonization
      or clinically obvious fungal infection at least on one occasion during the study.
      In addition to oral samples, fungi were identified in 9/23 pharyngeal swabs, 6/23
      urine and 1/23 blood cultures. The initial fungal pathogen was exclusively
      (33/33) Candida albicans. In extended severe neutropenic states, C. albicans was
      replaced by non-albicans species (C. kefyr, C. lusitaniae, C. sake, C.
      tropicalis) in 5 patients between 4 to 6 days of the neutropenic episodes. Four
      of the nonalbicans Candida strains were resistant to azole-type antifungal
      agents. Neutropenic episodes of children with cancer are associated with an
      increased risk of developing oral and even systemic infections with C. albicans
      that can be replaced by azole-resistant nonalbicans strains in prolonged
      neutropenia contributing to morbidity of these patients.

PMID- 17189990
TI  - Subcutaneous metastasis of peritoneal mesothelioma diagnosed by fine-needle
      aspiration.
AB  - Mesothelioma is a rare malignant neoplasm of the serosal membranes, which can
      give distant metastases in various organs in advanced stages of its course.
      Subcutaneous tissue is an unusual metastatic site. In the literature, only one
      case of metastatic mesothelioma to the skin of the face has been reported. We
      present a case of a 60-year-old female with a prior history of peritoneal
      malignant mesothelioma, who 6 months after the initial diagnosis presented with a
      subcutaneous nodule in the lateral chest wall. Cytological examination of the
      material obtained by FNA from the nodule revealed metastatic mesothelioma.
      Although subcutaneous metastasis of malignant mesothelioma is a rare entity, one
      must always keep this possibility in mind and proceed to further investigation of
      such lesions. In these cases, FNA is a simple diagnostic procedure for the
      identification of metastatic disease in patients with a prior history of
      malignancy.

PMID- 17189991
TI  - Malignant pilomatricoma in the parietal area.
AB  - A 27-year-old Japanese woman presented with a 2.5-cm nodular subcutaneous lesion
      in the parietal area. The nodule was well demarcated and situated in the dermis
      and subcutis. Histologically, the tumor was diagnosed as malignant pilomatricoma.
      The tumor was excised, the postoperative course was uneventful, no evidence of
      local recurrence or distant metastasis was observed, and the patient continues to
      be under close follow-up. Malignant pilomatricoma, a locally aggressive
      counterpart of benign pilomatricoma, is also referred to as pilomatrix carcinoma.
      Most cases are excised as benign tumors; however, when the excision is incomplete
      local recurrence is likely, and distant metastases have also been reported.
      Histologically, the diagnosis can be challenging because no clear histologic
      criteria are available. Because of the rarity of malignant pilomatricoma, no
      welldefined standards in the surgical management of this neoplasm have been
      established. Moreover, since distant metastases have been described, close
      followup of the lesion is requisite.

PMID- 17189992
TI  - Asymmetric calf hypertrophy of neurogenic origin.
AB  - A 47-year-old male presented with painful swelling of the right calf. His medical
      history was negative, except for a herniation of disc LIV-V 5 years before.
      Physical examination revealed unilateral calf hypertrophy with moderate weakness
      of plantarflexion, mild paresis of dorsiflexion. Electromyography showed a
      peripheral neurogenic lesion in the right anterior tibial muscle, but normal
      findings were obtained from the unaffected quadriceps muscle. Histological
      examination of the right gastrocnemic muscle showed neurogenic changes with
      typical targetoid fibers, but no pathological changes were present in the
      quadriceps muscle. Chronic asymmetric spinal muscular atrophy is an infrequent
      neuromuscular disease and because of asymmetric appearance, it might be difficult
      to distinguish from other, acquired neurogenic muscle diseases such as
      radiculopathy caused by intervertebral disc herniation. Our case confirms that
      muscular hypertrophy can follow partial denervation in humans.

PMID- 17189994
TI  - I've scheduled a vacation, but because of recent security restrictions I'm
      nervous about bringing my prescription medication on the plane. What should I do
      to make sure my medication passes a security check?

PMID- 17189995
TI  - What risk would you face if you joined a clinical trial?

PMID- 17189996
TI  - New pressure on hospitals to speed heart attack care.

PMID- 17189993
TI  - Severe endothelial dysfunction in the aorta of a mouse model of Fabry disease;
      partial prevention by N-butyldeoxynojirimycin treatment.
AB  - OBJECTIVE: Fabry disease results from alpha-gala-ctosidase A deficiency and is
      characterized by the lysosomal accumulation of globotriaosylceramide.
      Globotriaosylceramide storage predominantly affects endothelial cells, altering
      vascular wall morphology and vasomotor function. Our objective was to investigate
      aortic globotriaosylceramide levels, morphology and function in a mouse model of
      Fabry disease, and the effect of substrate reduction therapy, using the
      glycosphingolipid biosynthesis inhibitor N-butyldeoxynojirimycin. METHODS AND
      RESULTS: Mice used were C57BL/6J and alpha-galactosidase A knockout (Fabry). We
      show progressive accumulation of aortic globotriaosylceramide throughout the
      lifespan of untreated Fabry mice (55-fold elevation at 2 months increasing to 187
      fold by 19 months), localized to endothelial and vascular smooth-muscle cells;
      there was no effect on vascular wall morphology in young Fabry mice. In old mice,
      storage resulted in intimal thickening. Endothelial function declined with age in
      Fabry mouse aorta. Aortae from N-butyldeoxynojirimycin-treated Fabry mice at 19
      months of age had reduced endothelial globotriaosylceramide storage, fewer
      morphological abnormalities and less severe vasomotor dysfunction compared with
      untreated littermates. CONCLUSION: We provide evidence of a novel vascular
      phenotype in the Fabry mouse that has relevance to vascular disease in Fabry
      patients. N-Butyldeoxynojirimycin treatment partially prevented the phenotype in
      the Fabry mouse by reducing endothelial globotriaosylceramide storage.

PMID- 17189997
TI  - A cholesterol drug appears to lower cataract risk.

PMID- 17189998
TI  - How doctors respond to reports of device defects.

PMID- 17190000
TI  - Ask the doctors. My doctor of 31 years retired recently. My new physician seems
      like a competent young guy, but sometimes I want to check out what he tells me
      with my previous doctor, who in many ways was a friend. How can I do that, or is
      such an off-the-record consultation "just not done"?

PMID- 17189999
TI  - Ask the doctors. Does the aging but otherwise healthy body have a diminished
      capability to deliver oxygen to muscles during strenuous activity? Is there a
      role for supplemental oxygen during times of vigorous exertion? I have heard of
      "exercise with oxygen therapy," but know nothing of this practice.

PMID- 17190001
TI  - Early events in the thymus affect the balance of effector and regulatory T cells.
AB  - In cellular immunology the critical balance between effector and regulatory
      mechanisms is highlighted by serious immunopathologies attributable to mutations
      in Foxp3, a transcription factor required for a major subset of regulatory T (Tr)
      cells. Thus, many studies have focused on the developmental origin of Tr cells,
      with the prevailing view that they emerge in the thymus from late-stage T-cell
      progenitors whose T-cell receptors (TCRs) engage high affinity (agonist) ligands.
      This study questions the completeness of that interpretation. Here we show that
      without any obvious effect on TCR-mediated selection, the normal differentiation
      of mouse gammabeta T cells into potent cytolytic and interferon-gamma-secreting
      effector cells is switched towards an aggregate regulatory phenotype by limiting
      the capacity of CD4+CD8+ T-cell progenitors to influence in trans early gammabeta
      cell progenitors. Unexpectedly, we found that the propensity of early TCR
      alphabeta+ progenitors to differentiate into Foxp3+ Tr cells is also regulated in
      trans by CD4+CD8+ T-cell progenitor cells, before agonist selection.

PMID- 17190002
TI  - Does the pattern of repeated sprint ability differ between sickle cell trait
      carriers and healthy subjects.
AB  - Sickle cell trait (SCT) is a genetic abnormality affecting the synthesis of
      normal haemoglobin [Hb] and is the heterozygous form of sickle cell anaemia. The
      aim of the present study was to compare the ability to repeat maximal cycling
      sprints (RSA; repeated sprint ability) between SCT carriers (SCT group, n = 7)
      and a control group with normal haemoglobin [Hb] (n = 7). The two groups
      performed a 10-s maximal cycling sprint in order to determine the peak power
      output (P(peak10)). They then performed an RSA test that consisted of five 6-s
      maximal cycling sprints interspersed with 24 s of passive recovery. For each
      sprint, the peak power output (P(peak6)) and the work over the 6-s (W6) were
      calculated. The sum of each W6 developed during the test was considered to be the
      total work (W(tot)). The decrements over the repeated sprints for P(peak6)
      (P(6dec)) and W6 (W(6dec)) were also determined. We found no difference in
      P(peak10), W(tot) and W(6dec) between the two groups. However, the drop in
      P(peak6) and W6 during the RSA test appeared earlier in the SCT group and the
      decrease in P(peak6) over the RSA test was greater in the SCT group than in the
      control group (p < 0.05). In conclusion, we found that: 1) maximal anaerobic
      performance determined during a single sprint was not altered by SCT, but 2)
      repeated sprint ability was different in SCT carriers compared with sportsmen
      with normal Hb.

PMID- 17190003
TI  - Assessment of ventilatory thresholds from heart rate variability in well-trained
      subjects during cycling.
AB  - The purpose of this study was to implement a new method for assessing the
      ventilatory thresholds from heart rate variability (HRV) analysis. ECG, VO2,
      VCO2, and VE were collected from eleven well-trained subjects during an
      incremental exhaustive test performed on a cycle ergometer. The "Short-Term
      Fourier Transform" analysis was applied to RR time series to compute the high
      frequency HRV energy (HF, frequency range: 0.15 - 2 Hz) and HF frequency peak
      (fHF) vs. power stages. For all subjects, visual examination of ventilatory
      equivalents, fHF, and instantaneous HF energy multiplied by fHF (HF.fHF) showed
      two nonlinear increases. The first nonlinear increase corresponded to the first
      ventilatory threshold (VT1) and was associated with the first HF threshold
      (T(RSA1) from fHF and HFT1 from HF.fHF detection). The second nonlinear increase
      represented the second ventilatory threshold (VT2) and was associated with the
      second HF threshold (T(RSA2) from fHF and HFT2 from HF.fHF detection). HFT1 ,
      T(RSA1), HFT2, and T(RSA2) were, respectively, not significantly different from
      VT1 (VT1 = 219 +/- 45 vs. HFT1 = 220 +/- 48 W, p = 0.975; VT1 vs. T(RSA1) = 213
      +/- 56 W, p = 0.662) and VT2 (VT2 = 293 +/- 45 vs. HFT2 = 294 +/- - 48 W, p =
      0.956; vs. T(RSA2) = 300 +/- 58 W, p = 0.445). In addition, when expressed as a
      function of power, HFT1, T(RSA1), HFT2, and T(RSA2) were respectively correlated
      with VT1 (with HFT1 r2 = 0.94, p < 0.001; with T(RSA1) r2 = 0.48, p < 0.05) and
      VT2 (with HFT2 r2 = 0.97, p < 0.001; with T(RSA2 )r2 = 0.79, p < 0.001). This
      study confirms that ventilatory thresholds can be determined from RR time series
      using HRV time-frequency analysis in healthy well-trained subjects. In addition
      it shows that HF.fHF provides a more reliable and accurate index than fHF alone
      for this assessment.

PMID- 17190004
TI  - Protein interactions a la carte.

PMID- 17190005
TI  - Widening the protein crystallization bottleneck.
AB  - Two recent reports describe simple methods that may help expand the range of
      proteins amenable to crystallization.

PMID- 17190006
TI  - SIMS for membranes.

PMID- 17190007
TI  - Adult stem cells come up short.
AB  - New research demonstrates that terminally differentiated cells are more efficient
      than adult stem cells for cloning.

PMID- 17190008
TI  - Six degrees of separation.
AB  - A new resource allows researchers to match the gene-expression signature of their
      system of interest to that of well-characterized chemical compounds-a hypothesis
      generation tool with a bright future.

PMID- 17190009
TI  - Systems biology for beginners.
AB  - A web and print Focus on systems biology from Nature Publishing Group provides a
      practical introduction to a field that for all its promise still has many
      skeptics.

PMID- 17190010
TI  - Overcoming protein diversity on arrays.
AB  - Researchers show that to reliably establish protein interaction networks from
      microarray data it is necessary to measure saturation binding curves for each
      arrayed protein and its potential binding partners.

PMID- 17190011
TI  - Aquaculture in offshore zones.

PMID- 17190012
TI  - Malignant transformation of hypertrophic lichen planus.

PMID- 17190013
TI  - Asymptomatic nodule on lip.

PMID- 17190014
TI  - Trends in the expression of breastmilk 1993-2003.
AB  - The expression of breastmilk is an important strategy to enable mothers to
      continue exclusive breastfeeding. In some situations, for health or convenience,
      expressed breastmilk is required and infants fed this way still fall within the
      definition of exclusive breastfeeding. The aim of this study was to document the
      changes in rates of breastmilk expression between the first Perth Infant Feeding
      Study (PIFS I) in 1992-03 and PIFS II in 2002-03. The proportion of mothers
      expressing breastmilk peaked in the first six weeks, at 38% for PIFS I and 69%
      for PIFS II. The proportion of mothers who had expressed breastmilk had almost
      doubled in the decade between studies. The proportion of mothers expressing
      declined to about 28% of mothers at 22 weeks for PIFS II and slightly less in
      PIFS I. Breastmilk expression is a very useful skill to allow mothers to
      exclusively breastfeed until six months and should be taught to all mothers.

PMID- 17190015
TI  - Expressing and storing colostrum antenatally for use in the newborn period.
AB  - Colostrum is universally acknowledged as the perfect first food for infants.
      Oxytocin is the hormone of both labour and lactation but the literature shows
      that it does not always induce labour. A review of the custom of expressing
      antenatally by all women is followed by the maternal and infant medical reasons
      for expressing and storing colostrum. A suggested regime for expressing and
      storage of colostrum during pregnancy is included with advice about skin-to-skin
      contact in the first twenty-four hours to maximise breastmilk output in the long
      term.

PMID- 17190016
TI  - Ulcerative colitis, pregnancy, prenatal expression and breastfeeding.
AB  - I have been encouraged to share my breastfeeding experience, and in doing so I
      hope that it might help those in similar circumstances to make decisions, and
      also be of interest to health professionals working in lactation. I was diagnosed
      with ulcerative colitis at 28 years of age. The chronic inflammation of the colon
      is manifested by abdominal pain, painful diarrhea (sometimes with blood and
      mucous), weight loss and tiredness.

PMID- 17190017
TI  - A review of human milk banking and public health policy in Australia.
AB  - Breastmilk is the perfect food for human infants. It is markedly different from,
      and uniquely superior to, artificial baby milk. Human milk banks are services
      which collect, screen, process and distribute donated breastmilk. Recipients are
      generally ill and premature infants whose mothers are unable to breastfeed them.
      This review of human milk banking in Australian public health policy draws from
      local and international research. This history of human milk banking and
      contemporary Australian policies, pertaining to breastfeeding and milk banking,
      are examined. Human milk banking is noted to be largely invisible from national
      breastfeeding policies. The barriers to establishing human milk banks in the
      Australian context are explored. Strategies which have helped generate support
      for human milk banking are discussed. International research has demonstrated the
      cost-effectiveness of banked donor milk. It is time for human milk banking to
      become an integral component of Australian breastfeeding policies, viewed as one
      of several initiatives to protect and support breastfeeding.

PMID- 17190018
TI  - Carol Sakala's letter from North America: an uncontrolled experiment: elective
      delivery predominates in the United States.

PMID- 17190019
TI  - [Genital herpes].

PMID- 17190020
TI  - [The wet nurses of Jocotenango: gender, science, and politics in late colonial
      Guatemala].

PMID- 17190021
TI  - The creation of a Westphalian rye market 1820-1870: leading and following
      regions, a co-integration analysis.

PMID- 17190022
TI  - [The contribution of the French navy in the evacuation of auxiliaries and the
      European population of Algeria].

PMID- 17190023
TI  - [V International Conference on Functional Neuromorphology "Kolosov's Readings-
      2006". Abstracts].

PMID- 17190024
TI  - Necrobiotic panniculitis due to repeated insulin injection: a rare cause of a
      false positive somatostatin receptors scintigraphy.

PMID- 17190025
TI  - A need to redefine chronic pain?

PMID- 17190026
TI  - The association between the cervical spine, the stomatognathic system, and
      craniofacial pain: a critical review.
AB  - AIMS: Craniofacial pain is a term that encompasses pain in the head, face, and
      related structures. Multiple etiologies and factors may be related to
      craniofacial pain; however, the association between the cervical spine and its
      related structures and craniofacial pain is still a topic of debate. The
      objective of this critical review was to present and analyze the evidence of the
      associations between the cervical spine, stomatognathic system, and craniofacial
      pain. METHODS: A search of the databases Medline, PubMed, Embase, Web of
      Sciences, Cochrane Library, Cinahl, and HealthStar was conducted for all
      publications related to the topic in the English and Spanish languages. Relevant
      information was also derived from reference lists of the retrieved publications.
      The key words used in the search were cervical spine, cervical vertebrae, neck
      pain, neck injuries, neck muscles, craniofacial pain, orofacial pain, facial
      pain, temporomandibular joint pain, and temporomandibular joint disorders.
      RESULTS: The search provided information referring to the biomechanical,
      anatomical, and pathological association between craniofacial pain, the
      stomatognathic system and the cervical spine. CONCLUSION: The information
      provided by this review suggests an association between the cervical spine,
      stomatognathic system, and craniofacial pain, but most of this information is not
      conclusive and was derived from poor-quality studies (levels 3b, 4, and 5 based
      on Sackett's classification). Better designed studies are needed in order to
      clarify the real influence that the cervical spine has in relation to the
      stomatognathic system and craniofacial pain.

PMID- 17190027
TI  - The relationships among depression, pain, and masticatory functioning in
      temporomandibular disorder patients.
AB  - AIMS: To evaluate the effect of comorbid depression and pain on an early
      biopsychosocial intervention for acute temporomandibular disorder (TMD) patients.
      METHODS: Depressed (either current or lifetime; n=32) or nondepressed (n=31)
      acute TMD patients received a biopsychosocial intervention, and were evaluated at
      preintervention and again 12 months postintervention by Characteristic Pain
      Intensity, the Beck Depression Inventory, and a masticatory function test.
      RESULTS: Findings revealed that both depressed and nondepressed patients reported
      comparable pain decreases at 12 months postintervention. Moreover, there were no
      significant differences between patient groups in masticatory function.
      CONCLUSION: With appropriate early biopsychosocial intervention, acute TMD
      patients, regardless of the presence or absence of vulnerability to depression
      symptomatology, can be effectively treated.

PMID- 17190028
TI  - The impact of oral pain on quality of life during pregnancy in low-income
      Brazilian women.
AB  - AIMS: To assess the effects of oral pain on oral health-related quality of life
      during pregnancy and document measures taken by pregnant women seeking relief for
      oral pain. Their experience of other types of pain were also investigated.
      METHODS: A sample of pregnant women who were admitted to a public hospital to
      give birth were invited to participate in this cross-sectional study. Those who
      agreed were asked if they had experienced any pain due to problems with their
      mouth, teeth, or dentures during the 6 months prior to the interviews.
      Interviewees who answered affirmatively were questioned about the effects of this
      pain on their normal activities with the Oral Impacts on Daily Performances
      (OIDP) tool. RESULTS: The study population consisted of 504 subjects (83% of the
      eligible individuals). A high prevalence of untreated dental caries was found.
      The prevalences of oral pain, headaches, back pain, and pelvic pain were 39.1%,
      61.5%, 59.3%, and 60.9%, respectively. Of those reporting pain, 168 (33.3%)
      reported having had difficulty doing at least one of the activities included in
      the OIDP due to oral pain. The most frequently mentioned effects were difficulty
      in maintaining emotional balance (23.6%), difficulty eating (22.8%), and
      difficulty cleaning teeth (20%). The mean and median OIDP scores were 13.9% and
      8.0%, respectively. CONCLUSION: Oral pain during pregnancy was an important
      problem for this group of women and had a negative effect on their quality of
      life.

PMID- 17190029
TI  - Oral behaviors checklist: reliability of performance in targeted waking-state
      behaviors.
AB  - AIMS: To assess the consistency of intentional behavioral performance as an index
      of whether individuals understood the meanings of the behavioral terms of the
      Oral Behaviors Checklist, which is a self-report scale for identifying and
      quantifying the frequency of jaw overuse behaviors. METHODS: Surface
      electromyography was used to measure bilaterally the activity of the masseter,
      temporalis, and suprahyoid muscles (for assessment of oral behaviors) and the
      biceps muscles (reference task of biceps curl) in 27 temporomandibular disorder
      (TMD) cases and 27 controls. Subjects were asked to perform (1) biceps curls to
      lift 5 weights, with explanation, and (2) 10 oral behaviors (e.g., "clench",
      "yawn") without explanation. RESULTS: Biceps-curl performance resulted in
      assignments of excellent or very good for linearity-reliability based on
      inspection and correlation. Test-retest reliability of the 10 performed oral
      behaviors generally ranged from 0.6 to 0.98 for all 3 muscle groups, and many
      tasks had reliability coefficients comparable to those for the biceps curl.
      Across tasks, elevator muscle reliability of cases was 0.87, compared to 0.75 for
      controls; group values for opening muscles were similar. CONCLUSION: Individual
      subjects performed each task at a high level of consistency. Performance was not
      appreciably altered by being a TMD case versus a control and was not
      significantly different from the performance level of a reference task,
      indicating that each individual understood well the meaning of each oral behavior
      related word.

PMID- 17190030
TI  - The occurrence of spontaneous functional and nonfunctional orofacial activities
      in subjects without pain under laboratory conditions: a descriptive study.
AB  - AIMS: To assess the occurrence and the modality of spontaneous orofacial
      behaviors of awake healthy subjects without pain who were unaware of bruxism
      during wakefulness. METHODS: Sixteen asymptomatic subjects read silently for 30
      minutes while polygraphic recordings, including electromyographic (EMG) activity
      from masticatory and leg muscles, chest respiratory movements, and the movements
      and sounds of larynx, were made with simultaneous audio-video monitoring.
      Orofacial behaviors were scored based on the polygraphic and audio-video records.
      The activity and duration of masseter EMG bursts were calculated for the types of
      orofacial behaviors. RESULTS: The number of orofacial behaviors varied between
      subjects; swallowing was most frequently observed. Approximately half of the
      orofacial behaviors occurred closely with body movements. Of all masseter EMG
      bursts detected, 55% were associated with functional orofacial behaviors, while
      45% were regarded as nonfunctional. More than 80% of these masseter bursts lasted
      for less than 2 seconds, with an activity less than 20% of maximal voluntary
      clenching. These values did not differ between the types of associated orofacial
      behaviors. CONCLUSION: Although the occurrence of spontaneous orofacial motor
      activity is variable, asymptomatic subjects can exhibit substantial masseter
      bursts during wakefulness that are not associated with functional orofacial
      behaviors. The use of physiological and audio-video records permits spontaneous
      orofacial behaviors to be specifically identified, thereby allowing nonfunctional
      masseter EMG activity to be differentiated from functional masseter EMG activity.

PMID- 17190031
TI  - Influence of intramuscular nerve growth factor injection on the response
      properties of rat masseter muscle afferent fibers.
AB  - AIMS: To investigate whether local administration of nerve growth factor (NGF)
      decreases the mechanical threshold (MT) of putative nociceptive masseter afferent
      fibers as part of its mechanism of mechanical sensitization. METHODS:
      Electrophysiologic recordings were made from masseter afferents and a randomized,
      blinded approach was used to test the effects of intramuscular injection of NGF
      (2.5 or 25 microg/mL) into the rat masseter muscle on the MT of masseter
      afferents (n=65) and plasma protein extravasation. RESULTS: The plasma protein
      extravasation data and electrophysiological recordings indicated that rat NGF
      injection was not inflammatory and did not evoke afferent discharge or induce
      mechanical sensitization (as reflected in a decreased MT) in masseter afferents
      in either male or female rats. To investigate whether the lack of effect of NGF
      injection might be due to differences between human and rat NGF, additional
      experiments with human NGF injection (25 microg/mL) were undertaken.
      Intramuscular injection of human NGF into the rat masseter muscle also failed to
      evoke afferent discharges; however, it did decrease the MT of masseter afferent
      fibers. CONCLUSION: The finding that neither rat nor human NGF excited putative
      nociceptive masseter afferent fibers is consistent with a previous report that
      intramuscular NGF injections are not acutely painful in human subjects. The
      ability of human NGF injection into the rat masseter muscle to induce afferent
      mechanical sensitization suggests that this experimental approach may be useful
      for the study of peripheral mechanisms of myofascial pain and tenderness
      associated with temporomandibular disorders.

PMID- 17190032
TI  - Suitability of the cingulate cortex for neural control.
AB  - Recent neuroprosthetic work has focused on the motor cortex as a source of
      voluntary control signals. However, the motor cortex can be damaged in upper
      motor neuron degenerative diseases such as primary lateral sclerosis and
      amyotrophic lateral sclerosis. The possibility exists that prefrontal areas may
      also be used in neuroprosthetic devices. Here, we report the use of the cingulate
      cortex in a neuroprosthetic model. Seven rats were able to significantly modulate
      spiking activity in the cingulate cortex in order to receive reward. Furthermore,
      experiments with single neurons provide evidence that the cingulate cortex
      neuronal modulation is highly flexible and thus useful for a neuroprosthetic
      device.

PMID- 17190033
TI  - A component-based FPGA design framework for neuronal ion channel dynamics
      simulations.
AB  - Neuron-machine interfaces such as dynamic clamp and brain-implantable
      neuroprosthetic devices require real-time simulations of neuronal ion channel
      dynamics. Field-programmable gate array (FPGA) has emerged as a high-speed
      digital platform ideal for such application-specific computations. We propose an
      efficient and flexible component-based FPGA design framework for neuronal ion
      channel dynamics simulations, which overcomes certain limitations of the recently
      proposed memory-based approach. A parallel processing strategy is used to
      minimize computational delay, and a hardware-efficient factoring approach for
      calculating exponential and division functions in neuronal ion channel models is
      used to conserve resource consumption. Performances of the various FPGA design
      approaches are compared theoretically and experimentally in corresponding
      implementations of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) and N-methyl-D-aspartate (NMDA) synaptic ion channel models. Our results
      suggest that the component-based design framework provides a more memory economic
      solution, as well as more efficient logic utilization for large word lengths,
      whereas the memory-based approach may be suitable for time-critical applications
      where a higher throughput rate is desired.

PMID- 17190034
TI  - Inotropic effects of the K+ channel blocker 3,4-diaminopyridine: differential
      responses of rat soleus and extensor digitorum longus.
AB  - The K+ channel blocker 3,4-diaminopyrindine (DAP) increases diaphragm force, use
      of which could potentially improve muscle performance during functional
      neuromuscular stimulation. To determine the extent of hindlimb muscle force
      augmentation, and delineate whether DAP effects vary in muscles comprised of
      mainly slow versus fast fibers, rat soleus, extensor digitorum longus (EDL) and
      diaphragm muscle samples were studied in vitro. DAP increased force of all three
      muscles, but at high concentrations the force increases were transient and were
      followed by declines in force below baseline. The maximum DAP-induced twitch
      force increase was smaller for soleus (38 +/-7%) than both EDL (94+/-12%) (P <
      0.05) and diaphragm (93+/-13%) (P < 0.01). During fatigue-inducing 20 Hz
      stimulation (tested at an intermediate DAP concentration), force of soleus muscle
      remained significantly elevated by DAP for the entire testing period, force of
      DAP-treated EDL muscle rapidly declined to values in untreated muscle, and force
      of DAP-treated diaphragm had an intermediate force-time profile. Muscles varied
      in extent to which isometric contractile kinetics were altered by DAP. Thus, the
      K+ channel blocker DAP improves contractile performance of limb muscles, but the
      profile of improvement is distinct between the soleus and EDL muscles.

PMID- 17190036
TI  - Engineering better wheelchairs to enhance community participation.
AB  - With about 2.2 million Americans currently using wheeled mobility devices,
      wheelchairs are frequently provided to people with impaired mobility to provide
      accessibility to the community. Individuals with spinal cord injuries, arthritis,
      balance disorders, and other conditions or diseases are typical users of
      wheelchairs. However, secondary injuries and wheelchair-related accidents are
      risks introduced by wheelchairs. Research is underway to advance wheelchair
      design to prevent or accommodate secondary injuries related to propulsion and
      transfer biomechanics, while improving safe, functional performance and
      accessibility to the community. This paper summarizes research and development
      underway aimed at enhancing safety and optimizing wheelchair design.

PMID- 17190035
TI  - Very low-noise ENG amplifier system using CMOS technology.
AB  - In this paper, we describe the design and testing of a system for recording
      electroneurographic signals (ENG) from a multielectrode nerve cuff (MEC). This
      device, which is an extension of the conventional nerve signal recording cuff,
      enables ENG to be classified by action potential velocity. In addition to
      electrical measurements, we provide preliminary in vitro data obtained from frogs
      that demonstrate the validity of the technique for the first time. Since typical
      ENG signals are extremely small, on the order of 1 1 microV, very low-noise, high
      gain amplifiers are required. The ten-channel system we describe was realized in
      a 0.8 microm CMOS technology and detailed measured results are presented. The
      overall gain is 10 000 and the total input-referred root mean square (rms) noise
      in a bandwidth 1 Hz-5 kHZ is 291 nV. The active area is 12 mm(2) and the power
      consumption is 24 mW from +/-2.5 V power supplies.

PMID- 17190037
TI  - Kinematic design to improve ergonomics in human machine interaction.
AB  - This paper introduces a novel kinematic design paradigm for ergonomic human
      machine interaction. Goals for optimal design are formulated generically and
      applied to the mechanical design of an upper-arm exoskeleton. A nine degree-of
      freedom (DOF) model of the human arm kinematics is presented and used to develop,
      test, and optimize the kinematic structure of an human arm interfacing
      exoskeleton. The resulting device can interact with an unprecedented portion of
      the natural limb workspace, including motions in the shoulder-girdle, shoulder,
      elbow, and the wrist. The exoskeleton does not require alignment to the human
      joint axes, yet is able to actuate each DOF of our redundant limb unambiguously
      and without reaching into singularities. The device is comfortable to wear and
      does not create residual forces if misalignments exist. Implemented in a
      rehabilitation robot, the design features of the exoskeleton could enable longer
      lasting training sessions, training of fully natural tasks such as activities of
      daily living and shorter dress-on and dress-off times. Results from inter-subject
      experiments with a prototype are presented, that verify usability over the entire
      workspace of the human arm, including shoulder and shoulder girdle.

PMID- 17190038
TI  - Quantitative analysis of the ankle strategy under translational platform
      disturbance.
AB  - The ankle strategy is one of the postural adjustment maneuvers humans utilize
      when the support platform is disturbed. This paper presents a quantitative
      analysis of the ankle strategy. A three-link sagittal biped model is considered.
      The first link represents the two legs locked together. The second link
      represents the two thighs locked together. The third link represents the hip, the
      torso, the upper limbs, the neck, and the head. The dynamics, control, and
      stability of the three-link biped, under platform translation, are considered.
      The disturbance of the platform is represented as an input and the effect of the
      muscular system is reduced to a set of torques applied to the joints and across
      the joints. Two digital computer simulations are presented to demonstrate the
      behavior of the biped under backward or forward platform disturbance. The
      simulations are compared with experimental measurements of humans subjected to
      postural disturbances. It is shown that the effect of a horizontal disturbance at
      the ankle appears to be about 40 times that of the effect of the disturbance at
      the knees and at least a few hundred times larger than the effect of a
      disturbance at the hip. This means that, under translational platform
      disturbance, the ankle angle is subjected to the largest excursion. The knee and
      the hip angle excursions are relatively minor. Consequently, the biped, as a
      whole, appears to move as a single inverted pendulum. Major postural corrections
      are initiated by the ankle excursion. Further, when the available ankle torque is
      limited or nonexistent, the stability requires resorting to the knee or hip
      strategies.

PMID- 17190039
TI  - A comparative analysis of three self-balancing wheelchair balancing mechanisms.
AB  - In the last 20 years, three different basic, dynamic balancing designs have been
      proposed for a self-balancing wheelchair (SBW) that allows the wheelchair user to
      transition from driving on all four wheels to driving while balanced on the two
      large rear wheels. The dynamic performance of these three SBW designs, the
      hanging pendulum counterweight (HPC), the single inverted pendulum (SIP), and the
      double inverted pendulum (DIP), are compared when controlled by a common state
      space controller. The four dynamic performance considerations of stability,
      driver dynamic stress, maneuverability and technical requirements were used to
      compare these designs while performing the following five tests: 1) transition
      from four-wheel to two-wheel, balancing mode; 2) stationary, self-balancing
      stability when subjected to an impact disturbance; 3) movement initiation, and
      stopping while balancing; 4) response to impact disturbances while moving; and 5)
      stability on low traction surfaces. In addition, the movement initiation and
      stopping test was repeated with increased chair mass and inertia to investigate
      the sensitivity of model performance to changes in model parameters. After
      comparing the three models it was determined that the HPC mechanism is the best
      choice for further development based on the criteria of stability, driver dynamic
      stress, maneuverability, and technical requirements. The HPC ranked equal or
      better compared to the SIP and DIP on 15 of 29 stability and performance factors.
      It was also the only design that was stable for all normally expected driving
      conditions.

PMID- 17190040
TI  - Clearspeech: a display reader for the visually handicapped.
AB  - Many domestic appliances and much office equipment is controlled using a keypad
      and a small digital display. Programming such devices is problematical for the
      blind and visually handicapped. In this paper, we describe a device that may be
      used to read the displays on these devices. The device is designed to accept a
      description of the display being read, which specifies the types and locations of
      elements of the display. Images are captured using a handheld webcam. Images are
      processed to remove the distortions due to the camera orientation. The elements
      of the screen are interpreted and a suitable audio output is generated. In
      suitably illuminated scenes, the display data is interpreted correctly in
      approximately 90% of the cases investigated.

PMID- 17190041
TI  - A screen magnifier using "high level" implementation techniques.
AB  - This paper presents the architecture of, and the techniques used to build, a
      screen magnifier for visually impaired people that uses the "high-level" features
      of the Microsoft Windows operating system. The magnifier uses information from
      the Desktop Window as its source and overlays this with a topmost, transparent,
      layered window that contains the magnified image. Issues concerning cursor
      enlargement, tooltip suppression, and focus tracking are discussed. A stable
      magnifier results that does not need to use the "dirty" low-level techniques that
      are typically used to build screen magnifiers. The only known problem of the
      magnifier is that it fails to suppress the original, unmagnified cursor of the
      few applications that use custom cursors.

PMID- 17190042
TI  - Effects of linear versus sigmoid coding of visual or audio biofeedback for the
      control of upright stance.
AB  - Although both visual and audio biofeedback (BF) systems for postural control can
      reduce sway during stance, a direct comparison between the two systems has never
      been done. Further, comparing different coding designs of audio and visual BF may
      help in elucidating how BF information is integrated in the control of posture,
      and may improve knowledge for the design of innovative BF systems for postural
      control. The purpose of this paper is to compare the effects of linear versus
      sigmoid coding of trunk acceleration for audio and visual BF on postural sway in
      a group of eight, healthy subjects while standing on a foam surface. Results
      showed that sigmoid-coded audio BF reduced sway acceleration more than did a
      linear-coded audio BF, whereas a linear-coded visual BF reduced sway acceleration
      more than a sigmoid-coded visual BF. In addition, audio BF had larger effects on
      reducing center of pressure (COP) displacement whereas visual BF had larger
      effects on reducing trunk sway. These results suggest that audio and visual BF
      for postural control benefit from different types of sensory coding and each type
      of BF may encourage a different type of postural sway strategy.

PMID- 17190043
TI  - [Sociohygienic monitoring in the Russian Federation: problems and tasks].
AB  - The State sociohygienic monitoring (SHM) system is one of the most important
      mechanisms of providing sanitary-and-epidemiological well-being in the
      population. The March 30, 1999 Federal Law on Sanitary-and-Epidemiological Well
      being of the Population" refers SHM to as one of the mechanisms of state
      regulation in this field and defines as a state system for monitoring the
      population's health and the environment, for analyzing, evaluating, and
      predicting them, and for revealing cause-and-effect relations between the
      population's health status and the influence of environmental factors. Much work
      has been recently done to establish and manage a federal information fund (FIF)
      that is a database on the human health status and environment, based on long-term
      observations and an aggregate of normative legal acts and reference materials on
      the analysis of prediction and determination of cause-and-effect relations
      between the human health status and the influence of environmental factors. FIF
      obtains information from a great many sources, including databases of state
      executive authorities. This information is open and available to the institutions
      and organizations involved in the establishment of FIF. The elaboration and
      introduction of new, more informative indices for SHM management at the present
      stage are one of the urgent tasks. In accordance with the May 28, 2000 decision
      of the Board of the Ministry of Health of Russia, with the 2003-2004 regulatory
      documents of the Ministry of Health of Russia, much work to improve the list of
      SHM indices has been under way. The draft list of SHM indices is harmonized with
      the indices of the European SHN information system, with the list of social
      diseases, approved by the Russian Federation's Government Regulation No. 715
      dated December 1, 2004, and the list of national security threat indices (A 21
      2162 dated August 29, 2003). The draft list has been considered by the
      specialists of the Federal Service for Surveillance of Consumers' Rights
      Protection and Human Well-being; comments have been taken into account. The draft
      is under reconsideration and will require approval in the near future.

PMID- 17190045
TI  - [Role of ambient air pollution in the development of iron-deficiency anemia in
      the adult urban population].
AB  - The relationship of the man-made ambient air pollution to the primary incidence
      of iron-deficiency anemia (IDA) and disease-caused anemias was studied in the
      adult urban population. Man-caused ambient air pollution was established to serve
      as an etiological factor contributing to a reduction in leukocytic phagocytic
      activity and predisposing to the higher primary incidence of disease-caused iron
      deficiency and IDA.

PMID- 17190044
TI  - [Immunity and normal pharyngeal microflora in persons living in a technogenically
      exposed area].
AB  - The impact of industrial emissions of an aluminum plant of immunity and
      pharyngeal mucosal biocenosis were studied in healthy individuals living in the
      Sovetsky district. The effect of sodium fluoride in various concentrations on the
      activity of metabolic enzymes in the bacterial Staphylococcus epidermis cells
      isolated from the pharyngeal mucosa of the healthy individuals was also studied.
      The persons living in the Sovetsky district were found to have higher values of
      cellular immunity, an increase in the quantitative composition of the oral
      microflora being observed when its qualitative composition was worse. Various
      concentrations of sodium fluoride were ascertained to have a heterodirectional
      impact on microbial metabolism.

PMID- 17190046
TI  - [Hygienic assessment of a recirculatory combined air-conditioning extract-and
      input system in office building].
AB  - The high concentrations of lead were reveled in the air and dust of some premises
      and on the filters of a combined air-conditioning extract-and-input system in the
      high-rise office buildings located in the ecologically lead favorable
      environment. The dust content of lead in some premises on the first floors dust
      was as high as 200 mg/kg, which was more than 6 times higher than that in the
      soil at the highway near the office buildings. The use of new technologies and
      devices for cleaning and optimizing the air in the premises requires analytical
      studies to assess the quality of the environment, by taking into account the
      optimal conditions of their operation.

PMID- 17190047
TI  - [Ambient air lead levels and a risk for cardiovascular diseases in the residents
      of the Yamal region].

PMID- 17190048
TI  - [The hormonal status in the persons who are present in a chemical weapon
      deployment area].

PMID- 17190049
TI  - [Effect of monohydric aliphatic alcohols on children's health].
AB  - To form the evidence base of the "environmental determination" of disease is a
      topical line in human ecology and environmental hygiene. The widespread use of
      monohydric aliphatic alcohols in industry has determined the necessity of making
      an in-depth study of their toxic effects on man, by taking into account their
      actual concentrations forming in the blood. The results of the studies have led
      to the conclusion that the real risk of toxic exposure of an organism to
      monohydric alcohols forms when the blood concentrations of butyl alcohols, propyl
      alcohols, and methyl alcohol are over 0.03, 1.0-1.5, and 0.5 microg/kg/cm3,
      respectively. Toxic exposure involves immunosuppressive, oxidative, hematoxic,
      and sensitizing effects and impaired hepatic etherifying function. With the
      higher toxicity of the compounds, the damaging action of monohydric alcohols on
      the organism increases and the spectrum of abnormal clinical and laboratory
      parameters expands.

PMID- 17190050
TI  - [Impact of drinking water calcium and magnesium levels on morbidity in the Omsk
      Region].
AB  - Drinking water calcium and magnesium levels were examined for impact on morbidity
      in a model rural area of a West Siberian region. It was ascertained that there
      were negative correlations between the water levels of the above elements and the
      incidence of respiratory, gastrointestinal, and locomotor diseases and positive
      correlations between the concentrations of calcium and magnesium and the
      incidence of nervous, urogenital, and eye diseases. It is concluded that by
      adjusting the findings, the medical care availability factor should be taken into
      account in the investigations using the health indices calculated on the data
      from official medical accounts. This investigation has shown the estimation of
      the drinking water levels of calcium and magnesium as a significant hygienic
      problem for a model region.

PMID- 17190051
TI  - [The ecological and hygienic concept and experience in waste recycling in Astan].

PMID- 17190052
TI  - [To choice of UV-type equipment for affording air safety in the premises].

PMID- 17190053
TI  - [Immunity in those engaged in the manufacture of building materials under arctic
      conditions].
AB  - The investigation has demonstrated that the factors associated with the
      manufacture of building materials cause changes in workers' cellular, humoral,
      and nonspecific immunity. The found changes may be one the reasons for increasing
      the incidence of diseases in the workers. The more length of service and the
      longer period of residence in the Far North result to increased immune
      heterogenicity and depleted reserves of the immune system. Therefore, a combined
      influence of extreme climatic and geographical factors and a complex of permanent
      unfavorable industrial factors can substantially affect the immunity and health
      of an organism as a whole.

PMID- 17190054
TI  - [Impact of the working environment on metabolic reactions in operating pilots].
AB  - Two groups of male volunteers aged 35-45 years were examined. Group 1 comprised
      20 healthy donors controls) and Group 2 included 10 operating pilots whom after
      biochemical blood analysis were proposed to use daily the biologically active
      supplement (BAS) Kalifen, 5 ml (which was equal to 100 mg/day of total
      polyphenols) after meals in the morning for 4 weeks. Before the use of the
      supplement, the sera of the examinees provided evidence that they had
      hypertriglyceridemia and hypercholesterolemia, inhibited hepatic etherifying
      function, unbalanced phospholipid composition, depleted antioxidative system,
      enhanced lipid peroxidation, and increased erythrocytic membrane permeability.
      The combined influence of the working environment on the operating pilots's
      health status appeared as pronounced metabolic changes characteristic of those
      observed under physical and emotional stress. The use of Kalifen facilitated
      normalization of the studied biochemical parameters. From the afore-said, it is
      advisable to use BAS for the prevention of stress actions caused by a variety of
      physical and emotional agents.

PMID- 17190055
TI  - [Evaluation of the protective properties of nonwoven materials for throw-away
      medical overalls].
AB  - The permeability of varying density felts (Spandbond, SMS, Tyvek, Sontara) for
      throw-away medical overalls was experimentally assessed under statistic and
      dynamic conditions, by using model test aerosols, including bacterial one. Their
      permeability was shown to decrease with the higher density of the materials under
      study. Laminated Span-bond contributes to an abrupt reduce in the bacterial
      penetration of this kind of tissues and enhances their protective properties. The
      felts CMC, Tyvek, Sontara, and laminated Spanbond were found to have the highest
      protective properties. In terms of their barrier and protective properties, the
      felts surpass the tissues used to make re-usable protective medical overalls.

PMID- 17190057
TI  - [The half-board is a current model for formation of the health-preseving
      environment for junior schoolchildren].
AB  - The investigations have established that the hygienically founded organization of
      schooling and extraschool performance of gymnasia pupils levels increase
      educational and psychoemotional burdens. The contents and structure of a half
      board have been developed and substantiated as a current health formation system
      for junior schoolchildren in the innovational institutions. The introduction of
      the structural elements of a half-board into a gymnasium provides an efficient
      organization of a teaching-and-educational process and vital activity in junior
      schoolchildren, which in turn promotes better adaptability and qualitative
      academic achievement in the pupils.

PMID- 17190056
TI  - [The cytological status of the nasal mucosa and the buccal epithelium in coal
      miners].
AB  - Sixty-four persons were examined. The examination was undertaken to study the
      cytomophological parameters of the cells of the nasal mucosa and the buccal
      epithelium in coal miners. Group 1 consisted of 18 donors without contact with
      industrial dust; Group 2 comprised 24 apparently healthy miners; Group 3 included
      22 workers (drift miners) with Stage 1 anthracosilicosis, grade 1 respiratory
      failure. The patients with Stage 1 anthracosilicosis had noticeably worse
      morphofunctional characteristics of the epithelium that displayed extensive
      fields with pronounced structural changes, such as destruction and desquamation
      of the integumentary epithelium of the nasal mucosa. Nasal mucosal atrophic
      changes were observed in 50% of the examined miners. Examination of the buccal
      epithelium in apparently healthy miners (code 0) and in workers with Stage I
      anthracosilicosis revealed the increased proportion of microfloral
      (Streptococcus) contamination by 79% and 3.7 times, respectively.

PMID- 17190058
TI  - [Impact of the psychoemotional status of preschool children on the course of
      adaptive processes].

PMID- 17190059
TI  - [Influence of intraschool factors on pupils' mental performance and health
      status].
AB  - The study of the intraschool environment in the examined educational
      establishments has indicated that the sanitary and hygienic conditions of pupils'
      school stay are characterized by a diversity of disadvantages. The leading
      factors that have the greatest influence on schoolchildren's morbidity are those
      associated with the organization of a teaching-and-educational process (36.9%)
      and with the intraschool environment (28.1%). All the foregoing suggests that a
      hygienic monitoring system should be set up in each school for the systemic
      monitoring of pupils' health and for its forming factors.

PMID- 17190060
TI  - [The role of parents and school personnel in the organization of an early
      educational period in children].
AB  - The sociological study conducted in the Gorod Polevskoy, Sverdlovsk Region, has
      established that the prevalence of maladaptation was 22.3% in children after
      entering the first form. The major risk factors affecting the severity of an
      adaptive process are a history of diseases before going to school, nonattendance
      of organized pediatric collective bodies, disregarding the day regimen and a poor
      organization of a workplace, bad parental hygienic knowledge. Efforts aimed at
      preparing parents to organize a child's life in the first form are insufficient
      and their own steps are inadequate. The parents pay greater attention to the
      pedagogical aspects of adaptation, by forgetting the medical ones. The teachers
      and medical workers show a low level of hygienic knowledge of the manifestations
      of an adaptive period of children's entering school and their professional duties
      associated with the medical-and-pedagogical provision of this period and self
      overestimation of their competence.

PMID- 17190061
TI  - [Risks for developing diseases among pupils of educational establishments].

PMID- 17190062
TI  - [Immunological responsiveness in trained and untrained schoolchildren and
      students during a school year].
AB  - Examination of trained (43 skiers) and untrained senior schoolchildren (31 young
      males); low-order students-skiers (110 girls) and untrained students (17 girls);
      high-order students-skiers (n=39) and students not going in for sports (n=60)
      established that in school children and female students of both groups, the
      cellular and humoral immunogical changes were mainly seasonal: in spring versus
      autumn, a considerable reduction in the concentration of immunoglobulins (Ig) G,
      M, and A and circulating immune complexes (CIC) was attended by a significant B
      immunity system increase. In the high-order skiers, the time course of changes in
      immunological responsiveness depended on both a season and a muscle activity
      regime. In autumn with the start of intensive training loads, the vast majority
      of immune defense parameters (9/12) were significantly higher in the trained
      skiers than in the untrained. In spring versus autumn, despite a significant
      reduction in many cellular and humoral immunological parameters with a
      considerable increase in the count of T and B lymphocytes in both groups of
      students, many parameters, in particular the levels of T and B lymphocytes, IgG,
      and CIC usually remained higher in the sporting students than those in the
      untrained students of the same age.

PMID- 17190063
TI  - [Somatotype-dependent cardiorespiratory system adaption in children and
      adolsescents in the north-east of Russia].
AB  - The authors have revealed the tension of cardiovascular performance in 11-14-year
      old children and adolescents with the macrosomatotype (MaS) and a lower bronchial
      patency in 13-14-year-old adolescents in the winter-spring period. This points to
      the decreased reserves of the cardiorespiratory system in the teenagers with MaS
      during their adaptation the environment of the north-east of Russia.

PMID- 17190064
TI  - [Impact of aggressive assigment performance on the autonomic nervous systems in
      adolescents].
AB  - Impact of aggressive assignment performance on cardiac rhythm was studied in
      adolescents, by taking into account permanent aggressiveness and autonomic
      tendency in the examinees. The adolescents with high baseline aggressiveness were
      found to have a lower Kerdo autonomic index while the latter was not observed in
      those with low baseline aggressiveness. Aggressive computer games have been
      ascertained to have no negative impact and to have a beneficial effect on the
      adolescents' psychoemotional sphere.

PMID- 17190065
TI  - [Adolescents' physical activity].
AB  - The paper defines the parameters reflecting the physical activity of adolescents
      and their correlation with health and a risk of behavioral disorders, bad habits,
      and cravings. A total of 9499 Georgian adolescents aged 14-18 years, the senior
      (9th-llth-form) pupils, selected through two-step cluster sampling were surveyed.
      The pupils anonymously filled in special questionnaires. This yielded the
      parameters reflecting the intensity of physical activity of the adolescents and
      the latter's going in for sports. The parameters were shown to have a beneficial
      effect on health, including mental health, and on the magnitude of unhealthy
      behavior.

PMID- 17190067
TI  - [Erythrophagocytosis in rats long receiving sodium nitrite and alpha-tocopherol].
AB  - The effect of tocopherol in a dose of 150 mg/kg on the activity of
      erythrophagocytosis was studied in vitro during long-term nitrite intoxication.
      With sodium nitrite intake, activation of the cellular mechanisms of
      erythrodieresis was observed in all periods of an experiment, which caused blood
      cell changes. Administration of tocopherol in the presence of nitrite
      intoxication was found to reduce the phagocytic activity of macrophages, which
      prevented the development of anemia.

PMID- 17190066
TI  - [Evaluation of the efficacy of harmful agents].
AB  - A method is proposed to determine the efficacy of harmful agents, which is based
      on the assessment of a response of experimental animals by the mathematical
      statistical methods formalizing the approaches accepted in hygienic toxicology.
      It makes it possible to introduce a more detailed classification of their
      efficacy in accordance with the respective rather strict criteria. This method
      unifies this procedure to a great extent, thus lowering the influence of
      subjective factors, which lets us correctly solve the task of establishing the
      hygienic regulations. The results of evaluation of the efficacy of two
      combinations of the concentrations of copper, iron, chromium, and zinc contained
      in the drinking water are given as an example.

PMID- 17190069
TI  - [Use of a MFM 0142 membrane viral concentration module during sanitary and
      virological surveillance of water objects].

PMID- 17190068
TI  - [Experimental rationale for the maximum allowable concentrations of organic
      phosphorus toxic agents in the soil].
AB  - Hygienic standardization of soil sarin, soman, and Vx levels established the
      threshold and subthreshold concentrations of the agents from the general
      sanitary, translocational, and migratory water and migratory air safety indices.
      Substantiation of their maximum allowable concentrations (MAC), the limiting
      safety index is a migratory air index for soman and sarin and a migratory water
      index for Vx. Soil MACs of sarin, soman, and Vx are 2 x 10(-4), 1 x 10(-4), and 5
      x 10(-5) mg/kg, respectively.

PMID- 17190070
TI  - [Ozone water disinfection in recirculation-type swimming pools].

PMID- 17190071
TI  - [Isolation of water pathogens of parasitic diseases by means of a powder filter].

PMID- 17190072
TI  - Is lithium-ion safe?

PMID- 17190073
TI  - Outsourcing and the quality system.

PMID- 17190074
TI  - Who drank my wine?

PMID- 17190075
TI  - Laughter is the best medicine.

PMID- 17190076
TI  - CE staff helps develop new, cutting-edge facility in Ohio.

PMID- 17190077
TI  - Called to testify? It's 90 percent preparation, 10 percent deposition.

PMID- 17190078
TI  - Device manufacturers: a partner in quality assurance.

PMID- 17190079
TI  - EQ56: leveling the playing field for medical management.

PMID- 17190080
TI  - What is life-support equipment?

PMID- 17190081
TI  - Hot blooded: the basics of blood warmers.

PMID- 17190082
TI  - The nuts and bolts of...well...nuts and bolts.

PMID- 17190083
TI  - Quality of service: part 1.

PMID- 17190084
TI  - Troubleshooting phaco instruments.

PMID- 17190085
TI  - Clinical engineering toolkits for patient safety focus investigations.

PMID- 17190086
TI  - CAPA in the modern quality system.

PMID- 17190088
TI  - Making the transition from technologist to manager.
AB  - To prepare for the transition to management, technical personnel must (1) develop
      their administrative, communication, and interpersonal skills; (2) learn to
      delegate, and (3) learn management principles and concepts. This last activity
      can be accomplished through in-house management training programs, on-the-job
      training, or formal management degree programs. These activities will help
      increase the chances for success among technical personnel making the transition
      into management in a clinical or industrial setting.

PMID- 17190087
TI  - Robotic surgical systems.

PMID- 17190089
TI  - Switch software improves reliability of physiological network, patient safety.

PMID- 17190091
TI  - Steam sterilization do's and don'ts.

PMID- 17190090
TI  - An earthworm-like microrobot for colonoscopy.
AB  - Miniature robotics for colonoscopy has become a hot research topic with the
      development of minimally invasive surgery (MIS). In this paper, a novel
      microrobot for colonoscopy that operates based on a simulation of the squirming
      motion of the earthworm is described. The robot uses a unique driving unit called
      a linear electromagnetic driver. The prototype measures 9.5 mm in diameter and
      120 mm in length. It is driven by a linear direct current (DC) motor designed and
      manufactured by the authors. This paper describes the prototype, locomotion
      principle, and control system in detail. It then describes two models that were
      built to study the robot's ability to move in the viscoelastic colon environment.
      A slepe model of motion was developed and some mathematical evaluations of
      locomotion conditions were conducted. Experiments to test the creeping ability of
      the prototype on a slope were performed to verify these expressions. From the
      viscoelastic model relative to acting force between the robot and the colon, a
      transcendent equation about locomotive efficiency of the critical squirm step was
      deduced and solved to instruct the design of the robot. Last, in vitro
      experiments in the fresh colon of a pig were performed. The results show that
      this kind of microrobot can propel itself freely and reliably in the soft
      viscoelastic colon. Finally, future areas of research are noted.

PMID- 17190092
TI  - EMI education--a little knowledge.

PMID- 17190093
TI  - What resources are available for creating documents describing essential job
      functions?

PMID- 17190094
TI  - Changing the work environment to promote wellness: a focus group study.
AB  - It is estimated that employers spend more than 75 billion dollars annually on
      obesity-attributable health care. Interventions to reduce or prevent the risk of
      obesity are increasingly common at worksites and include health fairs, weight
      loss and nutrition classes, and fitness programs. However, many companies lack
      the resources to plan and implement these types of programs. Environmental
      approaches offer companies a low-cost option. A community-based participatory
      research model was used to bring academic researchers, human resources personnel,
      and health department educators together to plan and implement an environmental
      program aimed at increasing healthy eating and physical activity at four small
      manufacturing companies. The Diffusion of Innovations Theory guided the
      development of focus group questions. A focus group study was then conducted to
      gather information from employees and managers at these four companies. The
      questions identified workplace strategies that would aid in reducing barriers and
      developing appropriate communication channels to enhance employee participation
      in the program. The researchers identified themes from manager and employee focus
      groups regarding the following five environmental components: signs, walking
      paths, food changes, educational strategies, and advisory groups.

PMID- 17190095
TI  - Food safety in the workplace: a practical approach.
AB  - The occupational health nurse in a large manufacturing facility arrives at work
      early one Monday morning to find three ill employees in the clinic waiting room
      and a message from several plant supervisors that multiple employees have called
      in sick. The supervisors are concerned. The employees have reported similar
      symptoms, including nausea, vomiting, diarrhea, and fever Furthermore, two
      supervisors who rarely miss work have also called in sick and other employees are
      complaining of stomach cramps and diarrhea. The occupational health nurse
      promptly begins completing a nursing assessment and health history. She discovers
      that all sick employees attended the company picnic, catered by the facility's
      food service vendor, the day before. After notifying the local public health
      department, the occupational health nurse begins to investigate further. The
      occupational health nurse visits the cafeteria to speak with the manager and
      inquire about the food served at the picnic. The menu included ham and cheese
      sandwiches with mayonnaise, hamburgers, potato salad, and cake. The beverages
      were milk, non-bottled water, and lemonade. All leftover food was discarded, so
      nothing is available for testing. The manager mentions that yesterday was
      particularly hot, with a high of 93 degrees F. He states the local health
      department conducts regular, stringent food inspections. However, he admits they
      have been short staffed recently and, although he tries to provide adequate
      training and oversee all food service operations, a few new employees worked at
      the company picnic. He also mentions his holding temperature logs are "not
      exactly up-to-date." While talking to the manager the occupational health nurse
      notices one of the food service employees cutting raw vegetables on a wooden
      cutting board just used to cut raw chicken. The cutting board was wiped with a
      damp, visibly soiled sponge, rather than washed, after cutting the meat. It is
      abundantly clear that food safety training deficiencies exist in this food
      service. Seventy percent of the employees who attended the company picnic are too
      ill to work, and absenteeism leads to production shutdown. The culprit?
      Salmonella. Because of the number of cases, the local health department initiates
      an investigation and the facility is issued a citation.

PMID- 17190096
TI  - Preparing the work force for retirement--the role of occupational health nurses.
AB  - As baby boomers reach retirement, the need to develop realistic plans is
      pressing. Recent political and social developments involving Social Security,
      savings accounts, and pensions indicate a need for greater self-sufficiency. The
      greatest challenges facing retirees are maintenance of self-sufficiency,
      productivity, generativity, and social satisfaction. Employers can optimize the
      investment in their work force by implementing policies and work practices that
      take advantage of the improved cognitive functions of aging workers despite their
      declining physical abilities. Occupational health nurses have the skills in
      policy development, regulatory issues, and ergonomic principles to advise
      corporate leaders. Occupational health nurses can organize and present retirement
      planning skills to the work force in a variety of formats and with targeted
      content.

PMID- 17190097
TI  - Sleep deprivation: are you a victim?

PMID- 17190098
TI  - Treatment of natto, a fermented soybean preparation, to prevent excessive plasma
      vitamin K concentrations in patients taking warfarin.
AB  - The purpose of this study is to find a method of cooking natto that prevents the
      appearance of high-plasma vitamin K concentrations after the consumption of
      natto, so that patients taking warfarin can benefit from eating natto. Five
      cooking methods were examined to determine which could most effectively decrease
      the count of the living Bacillus subtilis in natto. Volunteers ate natto or
      treated natto, and their plasma vitamin K level was measured at 5, 8, 24 and 48 h
      thereafter. One gram of natto contained 9.7+/-0.1 Log cfu/mL of Bacillus
      subtilis. Boiling significantly reduced the Bacillus subtilis count to 5.1+/-0.3
      Log cfu/mL, and concomitantly reduced the content of menaquinone-7 (MK-7), which
      is a form of vitamin K synthesized by Bacillus subtilis, from 660.40+/-65.32
      ng/mL to 78.50+/- 11.12 ng/mL. Untreated natto increased the MK-7 concentration
      in blood from 1.86+/-1.51 ng/mL to 14.54+/-4.12 ng/mL at 5 h after intake, and
      the MK-7 concentration remained elevated at 8, 24 and 48 h (7.29+/-2.20, 6.97+/
      2.60, and 5.37+/-1.94 ng/mL, respectively). In contrast, boiled natto increased
      plasma MK-7 only mildly (from 1.61+/-1.11 to 4.02+/-0.82 ng/ mL at 5 h) and the
      concentration remained relatively stable up to 48 h (3.46+/-0.83, 4.22+/-1.51 and
      2.77+/-0.75 ng/mL at 8, 24 and 48 h, respectively). In conclusion, boiled natto
      did not cause a marked increase in the plasma concentration of vitamin K in
      subjects who consumed it. Thus, patients on warfarin may be able to eat boiled
      natto without ill effects.

PMID- 17190099
TI  - Effect of vitamin B6 deficiency on S-adenosylhomocysteine hydrolase activity as a
      target point for methionine metabolic regulation.
AB  - The objective of this study was to clarify the relationship between the
      accumulation of S-adenosylhomocysteine (SAH) and the change in the SAH hydrolase
      activity in vitamin B6 (B6). Male Wistar rats were fed a control diet (control
      and pair-fed groups) or B6-free diet (B6-deficient group) for 5 wk. Although the
      SAH-synthetic activity of SAH hydrolase significantly increased in the B6
      deficient group, SAH-hydrolytic activity of SAH hydrolase showed no significant
      difference in the liver among the three groups. On the other hand, SAH hydrolase
      mRNA in the liver did not show any significant change. Thus, the accumulation of
      SAH would be due to the increased SAH-synthetic activity of SAH hydrolase. The
      disturbed methionine metabolism by B6-deficiency, such as a significant increase
      of plasma homocysteine, might induce the activation of SAH hydrolase in the
      direction of SAH synthesis.

PMID- 17190100
TI  - Beneficial effect of pretreatment and treatment continuation with risedronate and
      vitamin K2 on cancellous bone loss after ovariectomy in rats: a bone
      histomorphometry study.
AB  - The purpose of the present study was to examine the effect of pretreatment with
      risedronate and/or vitamin K2 and treatment continuation with reduced dosing
      frequency of the drugs on the early cancellous bone loss induced by ovariectomy
      (OVX) in rats. Eighty female Sprague-Dawley rats, 4 mo of age, were randomized by
      the stratified weight method into eight groups (n= 10 in each group); rats
      subjected to OVX, but not sham-operated rats, were treated with vehicle,
      risedronate, vitamin K2 (menatetrenone), or risedronate+vitamin K2 for 4 wk
      before the surgery, and the treatment was either discontinued (pretreatment
      groups) or continued after the surgery (treatment continuation groups) for 2 wk.
      Sham-operated rats (controls) were treated with the vehicle throughout the
      experimental period. During the 4 wk prior to the surgery (pretreatment),
      risedronate and vitamin K2 were administered five times a week either
      subcutaneously at a dose of 2.5 microg/kg body weight (risedronate) or orally at
      the dose of 30 mg/kg body weight (vitamin K2). During the 2 wk after the surgery
      (treatment continuation), the dosing frequency of the drugs was reduced to twice
      a week. Risedronate and vitamin K2 had an anti-resorptive effect on the bone.
      Pretreatment with risedronate alone, but not vitamin K2 alone, prevented the loss
      of the cancellous bone volume/total volume (BV/TV) of the proximal tibial
      metaphysis after OVX. Treatment continuation with vitamin K2 alone prevented the
      loss of the cancellous BV/TV after OVX, while treatment continuation with
      risedronate alone increased the cancellous BV/TV to beyond the values in
      controls. Pretreatment with risedronate+vitamin K2 had a more beneficial effect
      in increasing the cancellous bone mass than pretreatment with risedronate alone.
      Treatment continuation with risedronate and/or vitamin K_ appeared to have a more
      beneficial effect in increasing the cancellous bone mass than the respective
      pretreatment. Neither the total tissue area nor the cortical area of the tibial
      diaphysis was affected by any treatment. The present study demonstrated that
      pretreatment with risedronate had a beneficial effect on the early cancellous
      bone loss after OVX in rats, with a more beneficial effect when combined with
      vitamin K2. Moreover, even though the dosing frequency of the drugs was reduced
      after OVX, treatment continuation appeared to be more beneficial than
      pretreatment for increasing the cancellous bone mass.

PMID- 17190101
TI  - Effect of the protein and oil contents on calcium utilization in the diets of
      female Fischer rats that were fed by three different feeding methods.
AB  - We studied the effects of varying the protein and oil contents in the diet and
      three different feeding methods on the utilization of dietary calcium (Ca) in
      female Fischer rats. The experimental diets were based on the AIN-76 diet. Rats
      were fed one of nine experimental diets containing different levels of protein
      and oil. The experimental diets contained 10, 20 or 40% of protein (milk casein)
      and 5, 10 or 20% of soybean oil. The three meal feeding methods were ad libitum
      feeding, pair feeding and adjustable feeding. The experimental diets that were
      given by prepared feeding were supplemented with a mineral and vitamin solution.
      The effects of the protein and oil contents in the diet were analyzed by two-way
      ANOVA. Among rats that were fed ad libitum, the oil content in the diet affected
      the degree of mineral and vitamin intake. Among the rats fed ad libitum, the oil
      content in the diet had a significant effect on the level of Ca intake, although
      it did not have a significant effect on the level of energy intake. For pair
      feeding, the feeding volume was limited in each group; therefore, there was a
      significant difference in energy intake and there was no significant difference
      in Ca intake among each diet group. For adjustable feeding, there was
      considerable mineral and vitamin intake, which effected the reduction of feeding
      volume depending on the oil volume in the diet. There were no significant
      differences in the energy, Ca and other mineral and vitamin intakes among the
      nine groups that were fed using adjustable feeding. In analyzing two-way ANOVA,
      in which the parameters were the contents of protein and oil in the experimental
      diets, there were differences in Ca utilization among rats that were fed using
      the three feeding methods. This result was shown to reflect on the difference as
      energy, mineral including Ca, and vitamin intake. However, the protein content in
      the diet had a significant effect on urinary Ca excretion in all three feeding
      methods. In addition, it was clear that the intake of protein and oil affected
      kidney calcification in all three feeding methods. The AIN Experimental Diet
      Committee reported that kidney calcification was found among rats that were fed
      the AIN-76 diet and that one of the causes of kidney calcification was the Ca/P
      ratio in this diet. The protein and oil contents in the diets had significant
      effects on the degree of kidney calcification among rats that were fed by pair
      feeding or adjustable feeding. The results of this study suggest that the protein
      and oil contents in the diet play an important role in kidney calcification.

PMID- 17190103
TI  - Characteristics of urine sodium and potassium after oral ingestion of solutions
      containing sodium and potassium which is isotonic to the physiological saline--a
      quantitative study.
AB  - The effects of orally ingesting 500 mL of four kinds of test solutions that were
      isotonic to physiological saline (i.e., containing sodium (Na) and potassium (K)
      as chloride with Na/K molar ratios of 1, 2, 3 and 4) on urine flow, Na and K
      excretions from Japanese male students were investigated. The subjects assembled
      at the National Institute of Nutrition the day before the oral ingestions, which
      were conducted three times for each subject. They were permitted to eat freely
      until 8:00 pm, and then the intake of food and drinks except tap water was
      prohibited until 10:00 pm. After that, no food or drinks except the test solution
      used, were permitted to be ingested until the end of the final collection of
      urine. Subjects were woken up at 7:00 am the next morning, at which time they
      emptied their bladder. At 8:00 am, after sampling control urine before ingestion,
      they ingested 500 mL of water, the physiological saline or one of the test
      solutions. Urine was collected every 30 min for 4 h after ingestion. Urine flow
      was significantly higher for those who drank solutions Na/ K = 1 and 2 than those
      who drank the saline (paired-t test), but that for those who drank solutions Na/K
      = 3 and 4 was not significantly higher. For those who drank solution Na/ k=2,
      urine Na was significantly higher than that of those who drank the saline 30 to
      60 min after ingestion. An increase in urine flow after K ingestion may be an
      essential factor for K-induced Na uresis.

PMID- 17190102
TI  - Genistein enhances antigen-specific cytokine production in female DO11.10
      transgenic mice.
AB  - Genistein is a phytoestrogen contained at high levels in soy products and has
      been shown to regulate immunoresponse. In this study, we evaluated the effects of
      genistein on the production of cytokines from antigen (Ag)-specific T cells using
      DO11.10 transgenic mice because the direct effect of genistein on Ag-specific
      cytokine production has not been elucidated. The oral administration of 20 mg/kg
      genistein increased IFN-gamma and IL-4 production from DO11.10+ T cells in
      response to ovalbumin (OVA)323-339 peptide in female DO11.10 mice. Analysis of
      intracellular cytokine synthesis revealed that the percentages of cytokine
      producing cells in the control and genistein-treated groups were not different,
      indicating that increased cytokine production occurred at the single-cell level.
      In contrast to the female mice, genistein did not increase cytokine production in
      male mice, suggesting that the effect of genistein on cytokine production is
      gender-dependent.

PMID- 17190104
TI  - Long-term administration of 4G-beta-D-galactosylsucrose (lactosucrose) enhances
      intestinal calcium absorption in young women: a randomized, placebo-controlled 96
      wk study.
AB  - This study determined the effect of long-term administration of 4(G)-beta-D
      galactosylsucrose (lactosucrose; LS) on intestinal calcium absorption. In a
      randomized, single-blind, parallel-group study, LS (n=9, 6.0 g twice daily) or a
      placebo (maltose; n=8, 6.0 g twice daily) was administered to healthy young women
      for 92 wk: the study also included a 4-wk post-administration period. All
      participants completed the study. Dietary nutrient intake; fecal weight, pH, and
      moisture content; fecal concentrations of short-chain fatty acids (SCFA),
      putrefactive products, ammonia, and minerals (calcium, magnesium, phosphorus, and
      iron); and serum calcium and osteocalcin concentrations were measured every 24
      wk. Urinary pyridinoline (PYR) and deoxypyridinoline (DPD), and urinary calcium
      excretion were measured every 12 wk. Significant effects of oligosaccharide
      treatment, time, and the interaction between oligosaccharide treatment and time
      were observed for fecal pH, SCFA, ammonia, and putrefactive product values
      (p<0.05). Fecal pH, ammonia, and putrefactive product values decreased in the LS
      group, and the fecal SCFA concentration significantly increased during the
      administration period; these changes were not observed 4 wk post-administration.
      To examine the mineral balance of calcium, magnesium, and phosphorus in detail,
      all the participants completed a 6-d mineral balance study, sometime between week
      56 and 60 of the longer study. During the mineral balance study, the daily
      calcium intake was set at 400 mg; all feces and urine were collected each day for
      6 d after an 8-d acclimation period. In the balance study, fecal calcium
      excretion was significantly lower in the LS group than in the placebo group
      (p<0.05), and apparent calcium absorption and retention, apparent magnesium and
      phosphorus absorption, and magnesium retention were significantly higher in the
      LS group than in the placebo group (p<0.05). Our results suggest that the
      administration of LS produces a long-term enhancement of intestinal calcium
      absorption in healthy young women with lower than recommended calcium intakes.

PMID- 17190105
TI  - Dietary sucrose enhances intestinal lactase gene expression in euthyroid rats.
AB  - It is postulated that dietary carbohydrates and thyroid hormones are major
      regulators for expression of the lactase/phlorizin hydrolase (LPH) gene in rat
      jejunum. In this study, we investigated the effects of thyroid hormones and
      dietary sucrose on LPH gene expression and lactase activity in starved rats.
      Firstly, animals at 8 wk of age were fed a low-starch diet (5.5% energy as
      cornstarch) or high-starch diet (71% energy as cornstarch) for 7 d (experiment
      1). The mRNA level of LPH as well as lactase activity significantly decreased in
      rats fed the low-starch diet as compared to those fed the high-starch diet. To
      investigate the effects of thyroid hormone status, the animals previously fed the
      low-starch diet were starved for 3 d, and half of the animals were given
      intraperitoneal (i.p.) injections of 20 microg/ 100 g body weight
      triiodothyronine (T3) twice daily (experiment 2). The LPH mRNA level and lactase
      activity were elevated by starvation for 3 d, but they were repressed by the
      injection of T3 during starvation. To investigate the effects of dietary sucrose
      in starved rats, they were force-fed a sucrose diet for 6 h (experiment 3). The
      LPH gene expression and lactase activity were up-regulated by force-feeding a
      sucrose diet, only when the animals were kept in euthyroid status by daily T3
      administrations. In contrast, the sucrase-isomaltase mRNA levels and sucrase
      activity were unaffected by force-feeding the sucrose diet for both T3-treated
      and untreated starved rats. Our work suggests that dietary sucrose is capable of
      enhancing lactase gene expression in starved rats when they have a sustainable
      thyroid hormone level.

PMID- 17190106
TI  - Impact of aging and beta3-adrenergic-receptor polymorphism on thermic and
      sympathetic responses to a high-fat meal.
AB  - The present study was designed to investigate the effect of aging and beta3
      adrenergic-receptor (beta3-AR) polymorphism on the thermic effect of meal (TEM)
      and sympathetic nervous system (SNS) response to a high-fat meal in 13 boys, 12
      young men, and 11 middle-aged men. SNS activity was assessed via power spectral
      analysis of heart rate variability. Significantly higher very-low-frequency (VLF)
      components associated with thermogenic SNS activity and energy expenditure per
      lean body mass (EE(LBM)) were observed in boys during the pre- and postprandial
      periods. There were no significant differences in VLF and EE(LBM) in the
      preprandial period between the young and middle-aged men. After feeding, however,
      the middle-aged men showed a significantly lower TEM (% test-meal energy) and VLF
      compared to the young men. A multiple regression analysis revealed that age was
      the only significant variable contributing to both TEM and VLF, but beta3-AR
      polymorphism and percentage of body fat were not statistically significant. In
      conclusion, age likely has a greater influence on TEM and SNS thermoregulation
      than genetic factors such as beta3-AR polymorphism, suggesting that this age
      related decrease in thermogenic response may be involved in the development of
      obesity among middle-aged men.

PMID- 17190107
TI  - Estimation of total daily energy expenditure and its components by monitoring the
      heart rate of Japanese endurance athletes.
AB  - The estimation of total daily energy expenditure (TEE) or the energy needs of
      athletes is important for maintaining a proper energy balance during training.
      This study was conducted to measure the TEE of Japanese middle- and long-distance
      runners using a heart-rate monitoring method (the HR method), and to ascertain
      the impact of three key energy expenditure (EE) components occurring within the
      day: sleep, exercise (training) and inactivity (other daily habitual activities).
      Additionally, energy balance was evaluated by comparing TEE with energy intake
      (EI). The mean TEE of six male athletes aged 19-21 y was 4,514+/-739 kcal/d and
      their mean EI was 3,784+/-91 kcal/d during the training period of 11 d. This
      negative energy balance led to a significant decline in body weight (p<0.01),
      indicating that proper care should be taken to balance energy during training.
      The mean daily EEs during sleep, inactivity, and exercise were 536+/-46 (12.0% of
      TEE), 1,722+/-145 (38.7%), and 2,255+/-658 (49.3%) kcal/d, respectively. There
      was a significant correlation between TEE and exercise EE (p<0.01) in the
      athletes. The TEE of the endurance athletes was higher than expected and
      significantly affected by exercise EE, indicating that the TEE of athletes, in
      general, must be carefully evaluated before incorporating nutritional support for
      them.

PMID- 17190108
TI  - The effects of calcium, phosphorus, magnesium, sodium, and zinc in improving the
      depression of gonadal development in growing male rats kept under a disturbed
      daily rhythm-investigations based on the L(16)(2(15))-type orthogonal array.
AB  - The purpose of this study was to clarify the effects of nutrients on the gonadal
      development of male rats kept under constant darkness as a model of disturbed
      daily rhythm. This experimental protocol was designed based on the L16(2(15))
      type orthogonal array, which can examine six factors. Five minerals (calcium
      (Ca), phosphorus (P), magnesium (Mg), sodium (Na), and zinc (Zn)) were selected
      as experimental factors, and the dietary content of these minerals was normal
      (AIN-76 diet) or 1/3.5 of the normal content. Lighting conditions (constant
      darkness or normal lighting) were also added as a factor. Four-week-old rats
      (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h
      light/dark cycle) for 4 wk. After 4 wk, the gonadal weights and serum
      testosterone content were evaluated. The lighting condition, Ca, Mg, and Na, and
      the interactions between the lighting condition and Ca, and Mg and Na were
      observed to affect the testes weight. Among the constant darkness groups (D
      groups), the highest value for testes weight was observed under the normal-Ca,
      normal-Mg, and normal-Na diet, and the lowest value was observed under the low
      Ca, normal-Mg, and low-Na diet. Among the normal lighting groups (N-groups), the
      highest value for testes weight was observed under the low-Ca, normal-Mg, and
      normal-Na diet, and the lowest value was observed under the normal-Ca, normal-Mg,
      and low-Na diet. Among the D-groups, the highest value for serum testosterone was
      observed under the normal-Ca, normal-Mg, and low-Na diet. Among the N-groups, the
      highest value was observed under the low-Ca, normal-Mg, and low-Na diet. It
      became clear that the amount of dietary Ca necessary for the gonadal development
      of rats increases when rats are kept under constant darkness as a model of
      disturbed daily rhythm compared with the normal lighting condition.

PMID- 17190109
TI  - Protein deficiency impairs DNA vaccine-induced antigen-specific T cell but not B
      cell response in C57BL/6 mice.
AB  - DNA vaccination is a simple method to induce antigen (Ag)-specific immunoresponse
      and has many potential advantages over other vaccines. Although people who need
      to receive vaccines often suffer undernutrition, there has been no study on a how
      nutritional status affects the immunoresponse induced by DNA vaccination. The aim
      of this study was to determine the relationship between protein deficiency and
      DNA vaccine-induced immunoresponses. C57BL/6 mice were fed a 5% or 20% casein
      diet for 30 d. The mice were immunized with an ovalubumin (OVA)-expression
      plasmid by the gene gun-based method three times at 10-d intervals. Body weight
      and serum albumin concentration in protein-deficient mice were significantly
      lower than those in mice fed the 20% casein diet (p<0.01, p<0.05). The percentage
      of OVA-specific CD8+ T cells was significantly decreased in the 5% casein group
      compared to that in the 20% casein group (p<0.05). Furthermore, CD4+ T cells from
      mice fed the low-protein diet showed lower interleukin (IL)-2 production than did
      those from the 20% group. In contrast to the T-cell function, protein deficiency
      did not affect OVA-specific Ab responses (p>0.05). These results suggest that
      protein deficiency impairs the induction of Ag-specific T-cell but not B-cell
      response in DNA-immunized mice. Our observation indicates that, in addition to
      development of an effective of DNA vaccine, the management of nutritional state
      is important for the prevention of infectious disease by DNA vaccination.

PMID- 17190111
TI  - Prune extract (Prunus domestica L.) suppresses the proliferation and induces the
      apoptosis of human colon carcinoma Caco-2.
AB  - Prunes are the dried fruits of certain cultivars of Prunus domestica L., and are
      recognized as a health food. The separated ethanol fraction from concentrated
      prune juice by DIAION HP-20 (PE) was investigated for cytotoxic effects on two
      different cancer cell lines in vitro. PE dose-dependently reduced the viable cell
      number of Caco-2, KATO III, but does not reduce the viable cell number of human
      normal colon fibroblast cells (CCD-18Co) used as a normal cell model. PE
      treatment for 24 h led to apoptotic changes in Caco-2 such as cell shrinkage and
      blebbed surfaces due to the convolutions of nuclear and plasma membranes and
      chromatin condensation, but this was not observed in CCD-18Co. PE induced
      nucleosomal DNA fragmentation typical of apoptosis in Caco-2 after 24 h of
      treatment. These results show that PE induced apoptosis in Caco-2. Furthermore,
      by Caco-2 treatment with H2O2 chelator catalase and Ca2+-chelator BAPTA/AM, the
      PE-induced cytotoxic pathway was completely blocked, and the viable cell number
      of Caco-2 was not affected.

PMID- 17190110
TI  - Effects of oral administration of ellagic acid-rich pomegranate extract on
      ultraviolet-induced pigmentation in the human skin.
AB  - We performed a double-blind, placebo-controlled trial to clinically evaluate the
      protective and ameliorative effects of ellagic acid-rich pomegranate extract on
      pigmentation in the skin after ultraviolet ray (UV) irradiation, using female
      subjects in their 20s to 40s. Thirteen healthy volunteers per group were randomly
      assigned to three groups; namely, high dose (200 mg/d ellagic acid), low dose
      (100 mg/d ellagic acid) and control (0 mg/d ellagic acid: placebo). Each group
      received the respective test foods for 4 wk. Each subject received a 1.5 MED
      (minimum erythema dose) of UV irradiation on an inside region of the right upper
      arm, based on the MED value measured on the previous day. Luminance (L), melanin
      and erythema values were measured before the start of the test food intake, and
      after 1, 2, 3 and 4 wk following the start of the test food intake. Further,
      questionnaires were conducted regarding the condition of the skin before the
      start of the test food intake and at the termination of the test food intake. As
      a result, decreasing rates of L values from the baseline in the low- and high
      dose groups were inhibited by 1.35% and 1.73% respectively, as compared to the
      control group. Further, a stratified analysis using subjects with a slight
      sunburn revealed an inhibited decrease of L values compared with the control
      group at 1, 2 (p<0.01, respectively) and 4 wk (p<0.05) after the start of the
      test food intake in the low-dose group, and at 2 and 3 wk (p<0.05) in the high
      dose group. Furthermore, the results of questionnaires showed ameliorating
      tendencies due to the test food, in some items such as "brightness of the face"
      and "stains and freckles." Based on the above-mentioned results, it is suggested
      that ellagic acid-rich pomegranate extract, ingested orally, has an inhibitory
      effect on a slight pigmentation in the human skin caused by UV irradiation.

PMID- 17190113
TI  - Teaching evidence-based practice: starting with the learner.

PMID- 17190114
TI  - Leadership strategies for uncertain times.

PMID- 17190115
TI  - A method for pattern recognition.
AB  - Although pattern is a dominant concept in nursing science, only Newman's method
      for recognizing pattern has been fully articulated and widely used in research
      about the human health experience. This article proposes an alternative, less
      costly method to facilitate research with larger numbers of participants in
      clinical settings. Cluster analysis, a quasi-quantitative technique, and content
      analysis were combined to produce a technique for recognizing patterns of person
      environment interaction. Results from two studies with persons experiencing a
      highly variable chronic illness, rheumatoid arthritis, indicated that this new
      approach identifies distinct common patterns of person-environment interaction.
      Sufficient detail about the nature of each pattern resulted to facilitate further
      knowledge development about the health experience and to provide guidance in
      structuring nursing care.

PMID- 17190116
TI  - Inspiratory muscle training: integrative review.
AB  - This article provides a critical review of inspiratory muscle training (IMT) in
      chronic obstructive pulmonary disease (COPD). Although extensive research on IMT
      has accumulated, its benefits have been debated, primarily because of
      methodological limitations of studies. Using relevant key words, multiple
      databases were searched from 1966. Selected studies used PImax (maximal
      inspiratory pressure) as an outcome variable. Overall, research demonstrated that
      a standard protocol of 30% or higher for a duration of 20 to 30 minutes per day
      for 10 to 12 weeks improves dyspnea and inspiratory strength and endurance with
      either inspiratory resistive or inspiratory threshold training. Regardless of
      method, IMT protocols for people with COPD and inspiratory muscle weakness and
      dyspnea are generally safe, feasible, and effective. Patient selectivity and
      study of subgroups are recommended.

PMID- 17190117
TI  - Understanding disgust in nursing: abjection, self, and the other.
AB  - From the seeming chaos of war zones and emergency rooms to the ritualized order
      of forensic psychiatric settings and sexual health clinics, nurses often
      experience feelings of disgust and repulsion in their practice. For these intense
      feelings to occur, an abject object must exist. Cadaverous, sick, disabled
      bodies, troubled minds, wounds, vomit, feces, and so forth are all part of
      nursing work and threaten the clean and proper bodies of nurses. The unclean side
      of nursing is rarely accounted for in academic literature: it is silenced. Using
      a theoretical approach, the objective of this paper is to demonstrate how
      fruitful the concept of abjection is in understanding nurses' reactions of
      disgust and repulsion regarding particular patients or clinical situations.

PMID- 17190119
TI  - An exciting future for respiratory nurses?

PMID- 17190118
TI  - Research testing of tailored interventions.
AB  - The purpose of this article is to offer rationale to support the argument for
      research testing of tailored interventions. The individualization of nursing
      interventions is used as a basis for discussion of the emergent need to test
      tailored interventions at the research rather than practice level. Both
      justification of efficacy and feasibility support the research testing of
      tailored interventions, in support of an evolving nursing process. In order to
      retain its patient-centered focus and yet meet scientific standards for practice,
      nursing must evaluate the individualization of care through more theory-based and
      systematic research processes. The testing of tailored interventions at the
      research level would provide a means to achieve these ends.

PMID- 17190120
TI  - Hospital at home for chronic obstructive pulmonary disease: an integrated
      hospital and community based generic intermediate care service for prevention and
      early discharge.
AB  - Recent randomized controlled studies have reported success for hospital at home
      for prevention and early discharge of chronic obstructive pulmonary disease
      (COPD) patients using hospital based respiratory nurse specialists. This
      observational study reports results using an integrated hospital and community
      based generic intermediate care service. The length of care, readmission within
      60 days and death within 60 days in the early discharge (9.37 days, 21.1%, 7%)
      and the prevention of admission (five to six days, 34.1%, 3.8%) are similar to
      previous studies. We suggest that this generic community model of service may
      allow hospital at home services for COPD to be introduced in more areas.

PMID- 17190121
TI  - Use of a chronic disease management programme in COPD to reduce hospital
      admissions.
AB  - Chronic obstructive pulmonary disease (COPD) accounts for a large number of
      hospital admissions and numerous interventions have attempted to reduce
      exacerbations requiring hospitalization. This paper describes the implementation
      of a community based COPD management programme led by a respiratory
      physiotherapist to improve home management of COPD and its effect on reducing
      readmissions and/or length of stay in hospital. One-hundred and twenty-five
      patients (median age 73) referred with COPD exacerbations met the criteria for
      the service; 95 received the intervention and data were available for 80. Median
      FEV1 was 0.86 L. Admission data, length of stay and total hospitalization days
      with COPD were compared for one year before and after the intervention. Overall
      there was no reduction in length of stay, admission frequency, or adjusted total
      hospitalization days with COPD, but median time interval to next exacerbation
      increased by 29%. In those who had had previous admissions (mean FEV1 0.58 L)
      total hospitalization days fell by 27%, length of stay fell by 58% despite an
      increase in admission frequency from one to two per year, and there was no change
      in median time interval to next hospitalized exacerbation. In our patients
      implementation of a Chronic Disease Management programme increased the time to
      next hospitalized exacerbation. Benefit was seen in the more severe patients
      however, with a significant reduction in both length of stay and total
      hospitalization days.

PMID- 17190122
TI  - The relation between measures of health status and quality of life in COPD.
AB  - Because quality of life (QoL) and health status (HS) scales contain different
      kinds of items and are shown not to be equivalent, there is a recommendation to
      use both types of scales. We investigated the relationship between either type of
      scale but focusing on the subscales of HS measures. A sample of chronic
      obstructive pulmonary disease (COPD) patients completed two QoL scales and two HS
      scales (BPQ and SGRQ), neuroticism, six-minute walk test and FEV1. Factor
      analysis revealed a two-factor structure (consistent with previous research), and
      showed that one type of HS subscale is different from QoL but another is
      equivalent to QoL. If total HS scores are used then it is valuable to include a
      QoL measure, but if HS subscales are reported, then these cover both latent
      variables, with the BPQ providing a clearer separation of the latent variables
      than the SGRQ.

PMID- 17190123
TI  - Further research on the Endurance Shuttle Walk Test (EWST) is needed before the
      test is advocated for clinical practice and research.

PMID- 17190124
TI  - Amyloidosis and the lung.
AB  - Amyloidosis is a disorder of protein folding in which normally soluble plasma
      proteins aggregate in an abnormal fibrillar form causing progressive disruption
      to tissue structure and organ function. This review covers systemic AA and AL
      amyloidosis which may arise as a consequence of chronic respiratory conditions;
      the manifestations of both systemic and of localised amyloid deposition within
      the respiratory tract and provides a summary of current approaches to diagnosis
      and management.

PMID- 17190125
TI  - Chronic respiratory care and rehabilitation in France.
AB  - The development of chronic respiratory care in France faces the same problems of
      ageing population, technological advancement and budgeting difficulties as other
      industrially developed countries. We describe the intermediate and home-care
      systems for treatment of chronic respiratory diseases.

PMID- 17190126
TI  - Long term oxygen therapy adherence and COPD: what we don't know.
AB  - Persons utilizing long term oxygen therapy (LTOT) at home suffer from chronic
      obstructive pulmonary disease (COPD). Adherence to LTOT ranges from 45% to 70%
      and utilization of 15 hours per day is widely accepted as efficacious. Although
      studies have reviewed the level of patient adherence with LTOT, few have
      introduced or evaluated interventions. The paucity of information regarding
      patients following oxygen prescription is an enormous void that must be tackled
      to augment clinical effectiveness and cost containment for the long term. A
      research agenda for LTOT adherence is postulated to help connect treatment
      adherence variables and concepts with clinical outcomes and quality of life.

PMID- 17190127
TI  - Current trends in medical ethics education.
AB  - The unprecedented progress in biomedical sciences and technology during the last
      few decades has resulted in great transformations in the concepts of health and
      disease, health systems and healthcare organization and practices. Those changes
      have been accompanied by the emergence of a broad range of ethical dilemmas that
      confront the health professionals more frequently in an increasing range of
      problems and situations. Health care that has been practiced for centuries on the
      basis of a direct doctor-patient relationship has been increasingly transformed
      to a more complex process integrating the health-team, the patient (healthcare
      seeker) and the community. Systematic review of the specialized literature
      revealed that Healthcare Ethics Education became a basic requirement for any
      training program for health professionals, and should cover the different stages
      of undergraduate, postgraduate and continuing education. Both theoretical
      foundations and practical skills are required for the appropriate ethical
      reasoning, ethical attitude and decision-making. There is growing evidence that
      physicians' professional and moral development is not determined by the formal
      curriculum of ethics, rather more, it is determined by the moral environment of
      the professional practice, the "hidden curriculum" which deserves serious
      consideration by medical educators.

PMID- 17190128
TI  - [Inflammatory heart diseases in childhood: Lebanese epidemiological survey].
AB  - OBJECTIVES: To study the frequency, prevalence, clinical presentation, management
      and outcome of inflammatory heart diseases (IHD) in Lebanese children. MATERIAL
      AND METHODS: Prospective survey of a group of children carriers (or at high risk)
      of an IHD (n: 156) recorded over a period of six years, between May 1st, 1999,
      and April 30th, 2005, at the National Register of Paediatric and Congenital Heart
      Disease, Lebanese Society of Cardiology. The diagnosis was confirmed in all cases
      by echocardiography. Cases related to cardiac surgery were excluded. RESULTS:
      Acute rheumatic fever (ARF) is the most frequent pathology : 35.9%, followed by
      Kawasaki disease (KD) : 24.4%, dilated cardiomyopathy (DCM) : 22.4%, pericardial
      effusion : 10.9% and finally infective endocarditis (IE) : 64%. There is a
      seasonal predominance for the ARF and KD during fall and early spring.
      Consanguineous marriage of first degree doesn't seem to be a factor predisposing
      for ARF and KD. ARF with carditis benefited from steroids with partial to total
      regression in 41/45 patients (91%), two patients underwent valve repair or
      replacement, another patient died from severe pancarditis. All children affected
      with KD (except 2 cases) received IV immunoglobulins (2 g/kg, single dose), and
      coronary aneurysms were observed in 2 patients (53%). Patients with DCM in whom
      there was a strong suspicion of viral myocarditis, were treated medically with
      complete recuperation of the cardiac function in 88% of cases. Among the patients
      with pericardial effusion, 3 needed urgent drainage because of a tamponnade. A
      child with IE was operated of his mitral valve and another one with cerebral
      palsy had a fatal outcome. No case of cardiac disease associated with HIV
      infection was found. CONCLUSION: In Lebanon, ARF remains the main cause of IHD
      during childhood, before KD. Currently, non-surgical treatments are highly
      efficient. Delayed diagnosis increased morbidity. Efforts are necessary for early
      recognition and primary prevention.

PMID- 17190129
TI  - [Control of blood pressure morning surge in a Lebanese hypertensive population].
AB  - OBJECTIVE: The primary endpoint of this prospective clinical study is to
      ascertain the degree of blood pressure control in the early-morning hours after 8
      weeks of treatment with Telmisartan in hypertensive patients using home blood
      pressure measurements. METHODS: Two hundred forty Lebanese patients with
      uncontrolled hypertension are enrolled in the study. The blood pressure is
      measured at the initial visit, then at week 4 of follow-up (optional visit) and
      after the 8 weeks period, by the physician at his office (with pulse rate) and by
      the patient at home in the morning. RESULTS: The blood pressure measured by the
      patient at home in the morning has a mean value of 129.7/79.1 mmHg, significantly
      less than 135/85 mmHg (P < 10(-1)), and it is reduced by 31.9/13.5 mmHg (P < 10(
      5)). At the physician's office, the reduction is 34.8/16 mmHg (P < 10(-4)). Heart
      rate is decreased by 4.7+/-0.5 bpm (P < 10(-5)). The drug was well tolerated.
      CONCLUSION: This study has demonstrated that Telmisartan, by his long half-life,
      protects the patients against the early-morning hours blood pressure surge,
      period during which coronary and cerebral events are the most frequent.

PMID- 17190131
TI  - [Microsurgical facial nerve decompression for hemifacial spasm].
AB  - PURPOSE: The results of a series of 8 patients with hemifacial spasm (HFS),
      treated with microsurgical vascular decompression (MVD) are reported. METHOD: A
      magnetic resonance imaging (MRI) of the brain was performed in all patients prior
      to surgery. The presence of arterial hypertension (HT) was noted. MVD was
      performed through a retromastoid approach, and Gortex was interposed between the
      nerve and the conflicting vessel. RESULTS: The offending vessels found were: the
      antero-inferior cerebellar artery in 50% of the cases, the postero-inferior
      cerebellar artery in 25% and the vertebral artery in 25%. These findings were
      positively correlated with MRI in only 50% of cases. The surgical results were
      the following: total and immediate relief in 62.5% of cases, delayed relief in
      25%, and partial relief in 12.5%. Neither failure, nor recurrence were noted. In
      terms of complications, two cases of persisting hearing loss, one case of
      transient hearing loss, and two cases of persisting facial palsy. Hypertension
      improved in 20% of cases. CONCLUSION: This study shows the success of MVD in the
      treatment of HFS. Intraoperative monitoring is helpful in reducing the
      complication rate. In our practice, the correlation between MRI findings and
      surgery was poor, as opposed to the results found in literature.

PMID- 17190130
TI  - Peripheral venous catheter-related inflammation. A randomized prospective trial.
AB  - BACKGROUND: Peripheral venous catheter-related inflammation (PVCRI) is a serious
      health and economic issue. It is mainly linked to peripheral venous catheter
      (PVC) duration and other risk factors. METHODS: PVCRI was prospectively evaluated
      in a 3 month-study according to PVC duration. Other risk factors were also
      studied such as age, gender, diabetes, intravenous steroids and antibiotics. 221
      patients admitted to 3 different departments in a university hospital were
      randomized to undergo a 72 hours versus 96 hours PVC. The primary endpoint was to
      evaluate if this prolonged duration would increase the incidence of lymphangitis.
      The secondary endpoints were to evaluate if other risk factors such as age,
      gender, diabetes, intravenous steroids and antibiotics, have a direct impact on
      lymphangitis. Fever, local inflammatory signs and date of occurrence have been
      noted by two different nurses. The Stata 8.0 program, and the Pearson chi-square
      test to compare percentages (alpha = 0.05) were used. RESULTS: PVCRI occurred in
      20.4% of all studied patients. PVCRI incidence did not differ between the
      patients who kept the catheter for 72 hours and those who kept it for 96 hours,
      but we found a significantly increasing incidence of PCVRI while comparing 24
      hours versus 48 hours duration and 24-48 hours duration versus 72-96 hours
      duration respectively. Age, as well as intravenous antibiotherapy showed to be a
      significant risk factor for PVCRI. As for diabetic patients, there was a trend
      towards a higher incidence of PVCRI. Intravenous steroids showed to have a
      beneficial effect. It is to be noted that the rate of PVCRI was significantly
      higher in the internal medicine/infectious diseases department compared to the
      two other departments. CONCLUSION: No difference on PVCRI risk was found between
      72 and 96 hours catheter duration. However the risk seems to increase between the
      first and the third day of catheterization. We suggest that an adapted duration
      of the PVC to the patient risks would be more cost-effective.

PMID- 17190132
TI  - [Obesity and related diseases in a Lebanese medical center].
AB  - INTRODUCTION: Obesity is actually a pandemic disease by itself, especially by its
      numerous associated complications. Obesity is considered among the most important
      cause of morbidity and mortality throughout the world. Its prevalence is variable
      between countries, but could be estimated to be around 20%. Few data concerning
      obesity is available in Lebanon. The objective of this study is to assess the
      prevalence of obesity in Lebanese patients consulting a primary care medical
      center in Beirut, as well as to study the links between obesity and other
      associated diseases. METHOD: Three hundred and thirteen patients, aged 13 years
      and above, consulting for the first time between 2000 and 2001 (one-year period),
      have been included in the study. Obesity is defined by a body mass index (BMI)>
      or =30 kg/m(2), and overweight is defined by a BMI between 25 and 29.9 kg/m(2).
      RESULTS: Among the 313 patients included, 22.1% were overweight, and 18% obese.
      The percentage of obesity is significantly higher in patients aged 40 years and
      above. No difference between men and women was observed. Obesity was
      significantly related to high blood pressure, diabetes, hypertriglyceridemia, low
      HDL and ischemic coronaropathy. CONCLUSION: Obesity and its associated diseases
      are frequently encountered problems in Lebanon, as it is in the rest of the
      world. Wider national studies are needed to define more accurately the magnitude
      of the problem, in order to apply efficient prevention strategies.

PMID- 17190133
TI  - [Lumbar synovial cysts : six case studies].
AB  - OBJECTIVES: The purpose of this study is to discuss the clinical and radiological
      aspects as well as the controversies in the management of lumbar synovial cysts.
      METHODS: We report a retrospective analysis of a series of 6 cases of lumbar
      synovial cysts. Patients presented with unilateral radicular pain mimicking a
      disc herniation. An MRI (magnetic resonance imaging) was performed in all
      patients. A computerized tomography scan was performed in one case and X rays in
      2 cases. All patients were operated on and the cyst resected. Arthrodesis was not
      performed in any of our patients. RESULTS: Functional outcome was marked by a
      significant improvement. Excellent results were found in 4 patients. Three
      patients who presented with a motor deficit recovered after the surgery.
      CONCLUSIONS: Lumbar synovial cysts should be considered in the differential
      diagnosis of any radicular compression. MRI is the examination of choice.
      Surgical resection is the definitive treatment with low rates of complications
      and recurrences.

PMID- 17190134
TI  - [Ultrasound guided vacuum breast biopsy for microcalcifications in a male. First
      case report].
AB  - The author reports the case of a man presenting with a bloody discharge from the
      right nipple without a palpable mass. On the mammogram pleiomorphic
      microcalcifications were identified (BIRADS-Category 4B). An ultrasound guided
      mammotome vacuum-assisted biopsy (11-G) was done, because the breast was thin and
      the microcalcifications were seen by ultrasound. This is the first case report of
      a biopsy performed under ultrasound guidance for a man with breast
      microcalcifications. The diagnosis of DCIS was confirmed by pathology.

PMID- 17190135
TI  - Visual field changes in methotrexate therapy. Case report and review of the
      literature.
AB  - PURPOSE: To present a unilateral central visual field defect in a patient with
      psoriatic arthritis treated with Methotrexate and folic acid supplement, probably
      induced by toxic posterior optic neuropathy. The scotoma incompletely resolved
      after cessation of Methotrexate (MTX) therapy. METHODS: Serial fundoscopic,
      perimetric and electrophysiological examination as well as comprehensive
      neurological investigation including lumbar puncture, carotid sonography,
      electroneurography, and MRI of the brain. RESULTS: A female patient with
      psoriatic arthritis on long-standing Methotrexate (MTX 15 mg IM/once a week)
      therapy suffered first from an acute attack of central visual field defect in her
      right eye and later on from two subsequent deteriorations of her scotoma within
      one year. A demyelinating retrobulbar optic neuritis was excluded through
      repeated comprehensive neurological investigations and unresponsiveness to
      systemic corticosteroid therapy. A MTX-induced posterior optic neuropathy was
      suspected and the patient experienced improvement of her visual field defects
      only six weeks after discontinuing MTX therapy. Further improvement was observed
      through follow-up perimetric examinations half a year after cessation.
      CONCLUSIONS: Central scotoma with unremarkable optic disc can occur after long
      standing treatment with MTX and despite folic acid supplementary therapy. This is
      most probably due to posterior optic neuropathy. Early cessation of the drug or
      change to another antimetabolite therapy can stop the deterioration of the visual
      field changes and even improve them. The exact pathomechanism is still unclear
      and the involvement of only one eye requires more investigation. MTX-induced
      posterior optic neuropathy should be included in the differential diagnosis of
      toxic optic neuropathy. This is getting more frequent than before because of the
      nowadays standard use of MTX in treatment of many autoimmune collagen diseases.

PMID- 17190136
TI  - Fibro-osseous and respiratory epithelial hamartoma of the fronto-ethmoid region.
AB  - A 31-year-old lady presented to the otorhinolaryngology clinic complaining of
      right exophtalmus. Imaging studies revealed a right frontal sinus mass,
      suggestive of a mucocele, and fronto-ethmoidal ground glass opacification. In the
      operating room, the frontal sinuses were exposed through an osteoplastic flap,
      and connected to the nasal cavity through a Lothrop-like drainage pathway. The
      pathologic analysis revealed a frontal sinus mucocele and fibro-osseous and
      respiratory epithelial hamartoma of the fronto-ethmoid region. In this case
      report, this rare pathology is discussed, in addition to a thorough elaboration
      upon the surgical options as dictated by the anatomic complexity of the region.

PMID- 17190137
TI  - Increased urinary albumin excretion: definition, prevalence, clinical
      significance and therapeutic implications.

PMID- 17190138
TI  - [Improved method of acute myocardial ischemic rat model].
AB  - OBJECTIVE: To improve the successful rate of operation and the livability in
      establishing acute myocardial ischemic rat model. METHODS: The successful rate of
      animal experiment is compared between traditional method and improved method.
      RESULTS: The successful rate of improved method was 90%, which was much higher
      than 30% in successful rate of traditional method. CONCLUSION: The improved
      method may reduce the difficulty of operation remarkably and cut down the
      experiment expenditure, which is superior to traditional method.

PMID- 17190139
TI  - [Dynamic observation of brainstem auditory evoked potential and pathological
      changes of the brain after closed brain injuries in rats].
AB  - OBJECTIVE: To investigate the dynamic experiences of pathological changes in
      brain and the injured role of brainstem auditory evoked potential (BAEP) after
      closed Mild Traumatic Brain Injury (MTBI) in rat. METHODS: A closed diffuse brain
      injury model was successfully produced in rat by hit the parietal bone with a
      spring-droved steel stick. The auditory brainstem response evoked by click at
      50Hz stimulating frequency were recorded at pre-trauma, 15 min and 1, 3, 6, 12 h
      and 1, 2, 4, 7, 10, 14, 21 d after brain injury. The pathological changes of
      brain were observed under light microscope and the brain edema was detected by
      wet weight/dry weight rations. RESULTS: The I-V, III-V of BAEP wave inter peak
      latency (IPL) in MTBI group increased immediately in 15 minutes after injury. The
      III, V wave peak latency (PL) and I-V, III-V wave IPL became longer than the pre
      trauma level in 6, 12 h post-injury (P<0.05). The III, V wave PL and I - III, I -
      V, III - V wave IPL became longer than the pre-trauma level in 1, 2 d after
      injury (P < 0.001), the BAEP retuned to normal level in 14 d after brain injury.
      At 15 minutes after injury, the water content in brain increased and met its peak
      in 1 d, decreased gradually in 4 d, then decreased slowly and returned to normal
      level in 10 d after injury. CONCLUSION: The regular changes of BAEP could be an
      objective tool for evaluating hearing dysfunction after closed mild diffuse
      traumatic brain injury.

PMID- 17190140
TI  - [Accuracy of age estimation in 14-year-old females by two skeletal age
      standards].
AB  - OBJECTIVE: To study the accurate of Li Guozhen's Percent Numeration and the
      Development Standard of Chinese Wrist Bone CHN Numeration of age estimation in 14
      year-old females. METHODS: Fifty-one 14-year-old females from three middle
      schools in Loudi City in Hunan were selected randomly, whose left wrists were
      photographed with X-rays under the same condition. Skeletal age was estimated
      following the two numerations. The two skeletal ages were compared with each
      other and with chronological age. RESULTS: The skeletal age from Percent
      Numeration and CHN Numeration have no significance difference, P > 0.05. And the
      skeletal ages of the two Numerations have no significance difference either, P >
      0.05. CONCLUSION: The Percent Numeration and the CHN Numeration are still suited
      for age estimation in 14-year-old females.

PMID- 17190141
TI  - [Apoptosis in myocardial cells after macleaya cordata total alkaloids poisoning
      in rats].
AB  - OBJECTIVE: To observe pathological changes and apoptosis in rats myocardial cells
      after Macleaya cordata total alkaloids poisoning, and to provide some references
      for Macleaya cordata total alkaloids poisoning detection. METHODS: An
      experimental model of Macleaya cordata total alkaloids poisoning was established,
      and the technology of TUNEL staining was used.The results were analyzed by
      computer image analysis competitive system. RESULTS: Quantities of apoptosis in
      myocardial cells in poisoning groups were much more than those in the control
      groups at different tages (P<0.01). In addition the quantities of apoptosis were
      different after different poisoning duration. CONCLUSION: Although clinical
      symptoms was not obvious and could not be detected by poison analysis.
      Pathological changes induced by Macleaya cordata total alkaloids could be found
      through the apoptosis detection.

PMID- 17190142
TI  - [Expression of c-myc protein on rats' brains after brain concussion].
AB  - OBJECTIVE: To study the changes of expression of c-myc protein on rats' brains
      after brain concussion. METHODS: sixty rats were randomly divided into brain
      concussion groups and control group. The expression of c-myc protein was
      microscopically observed by immunohistochemical method. RESULTS: No expression of
      c-myc protein in control group were observed. However, positive expression of c
      myc protein in some neurons was seen at 20 min after brain concussion, and reach
      to the peak at 8h after brain concussion and then decreased gradually.
      CONCLUSION: These findings suggest that the detection of c-myc protein could be
      an index of diagnosis of brain concussion.

PMID- 17190143
TI  - [Comparative study for the methods on measuring intracranial hemorrhage volume].
AB  - OBJECTIVE: To explore a method of measuring intracranial hemorrhage to be applied
      in clinical forensic science. METHODS: The accurace of the methods of Tada
      formula, Stereology and Software boundary to measure intracranial hemorrhage and
      their practicability were compared. RESULTS: The measured results of Stereology
      and Software boundary are precise, but the irregularity haematoma volume measured
      by the method of Tada formula has a high error value. CONCLUSION: The method of
      stereolgy is the best in measuring intracranial hemorrhage for clinical forensic
      science.

PMID- 17190144
TI  - [Comparison of retrograde amnesia changes within different injury levels of
      cerebral concussion in rats].
AB  - OBJECTIVE: To investigate the retrograde amnesia changes within different injury
      levels of cerebral concussion in rats. METHODS: A metallic pendulum striker
      device of brain injury was deployed to duplicate CC models of different injury
      levels within Sprague-Dawley (S-D) rats. The investigated animals were divided
      into two groups according to classification standard, that is, Pure Cerebral
      Concussion (PCC) group and Complicated Cerebral Concussion (CCC) group. One
      control group was used, and each group included 8 animals. The retrograde amnesia
      of each group was assessed by Morris Water Maze (MWM) Test from 3 days preinjury
      to 7 days postconcussion. RESULTS: Compared with the control group, the
      retrograde amnesia was detected within 3 days in PCC group, and 5 days in CCC
      group after injury. At the same time, the two groups both manifested space
      recognition deficit. CONCLUSION: The retrograde amnesia existed in both pure
      cerebral concussion group and complicated cerebral concussion. Furthermore, the
      lasting time of retrograde amnesia in animals correlates to the injury level of
      brain concussion.

PMID- 17190145
TI  - [Comparison of objective assessment using the sweep pattern visual evoked
      response acuity (SPVERA) and illiterate E visual acuity].
AB  - OBJECTIVE: To compare the vision objectively assessed by SPVERA with the
      illiterate E Acuity in normal subjects. METHODS: The effect of artificially
      induced image defocusing on visual acuities (Vas) measured by SPVEP and
      illiterate E chart measurement was studied in 14 normal subjects. SPVEP was
      recorded using vertical gratings of 8 different spatial frequencies ranging from
      0.235 9 to 30.203 2 c/deg. The responses were averaged and displayed through the
      discrete Fourier transform on the monitor display. SPVERA was determined by
      extrapolating the PVER amplitude -spatial frequency function to baseline. SPVERA
      was compared with illiterate E visual acuity measured under the same conditions
      of optical defocus. RESULTS: With moderate defocusing (<+1.0 diopter (D),VA >
      0.42), the SPVERA were equal to or poorer than the illiterate E visual acuity.
      With more defocus (> +2.0 diopter (D), VA < 0.3),the SPVERA became better than
      the illiterate E chart Visual Acuity. The correlation between the two acuities
      was r2 = 0.919. CONCLUSION: SPVERA and the illiterate E visual acuity correlated
      to a certain degree. We conclude that the SPVERA is effective in estimating
      vision objectively.

PMID- 17190146
TI  - [Relationship between human age and mtDNA 4977 deletions in human blood cells].
AB  - OBJECTIVE: To study the relationship between human age and mtDNA 4977 deletions
      in human blood cells. METHODS: According to Anderson's sequence, two sets of
      primers were designed. Human mtDNA 4977 deletions in blood samples from 110
      healthy human individuals in different age groups were examined by using Real
      time quantitative PCR. RESULTS: The mtDNA 4977 deletions could be observed unless
      the age was under 23 years old. The older the people were, the easier the
      deletion could be observed. CONCLUSION: mtDNA 4977 deletions in human blood cells
      were correlated with human ages in some extent.

PMID- 17190148
TI  - [Determination of methamphetamine in whole blood by capillary zone
      electrophoresis after solid phase extraction].
AB  - OBJECTIVE: To develop a specific CZE method for the determination of
      methamphetamine in whole blood after solid phase extraction. METHODS: With the
      doxapram as internal standard, Oasis column was used to extract drugs from whole
      blood and the sample was analysized by CZE. RESULTS: The method showed excellent
      linearity and the linear correlation coefficient was 0.994. The relative standard
      deviation for between-day and within-day were 5.31% and 2.22%, respectively.
      CONCLUSION: The method is effective, simple, reliable and has been used in the
      determination of methamphetamine in whole blood.

PMID- 17190147
TI  - [Analysis of 37 drugs in whole blood by HPLC after solid phase extraction].
AB  - OBJECTIVE: To develop a specific, sensitive, reproducible SPE-HPLC method for the
      determination of 37 drugs in whole blood. METHODS: With the doxapram as internal
      standard, Oasis column was used to extract drugs from whole blood. Two kinds of
      mobile phases were used in this study. Separations were achieved by a LiChrospher
      100 RP-C18 (250 mm x 4.0 mm x 5 microm) column kept at 50 degrees C, the DAD
      detector was set at 230 nm and 250 nm. RESULTS: The limit of detection were 1-30
      ng/mL. The method showed excellent linearity and the linear correlation
      coefficient was > or =0.997 98. The relative standard deviation for between-day
      and within-day assay were <10%. CONCLUSION: The method is effective, simple,
      reliable and has been used in real cases.

PMID- 17190149
TI  - [Forensic identification of floating shoulder injury].
AB  - OBJECTIVE: To discuss forensic identification of floating shoulder injury (FSI).
      METHODS: To analyze fifteen cases of FSI which were accepted from Jan. 1993 to
      Jan. 2006, including 15 shoulder neck fracture, 13 clavide stem fracture and 2
      distal end clavide fracture, the function of shoulder joint was evaluated six
      months after injure considering the following three aspects: result of forensic
      examination such as X-ray photograph, CT and MRI, the injurers' symptom,
      objective sign and joint function, shoulder joint territory, degree of pain and
      local muscle power. RESULTS: Basing on the curative effect standard of Herscovic,
      all cases were divided into good. Modest, worst, which included 2, 4, 9 cases
      respectively; referring the standard of GA35-92, GB18667-2002, all cases were
      divided into six, seven, eight, nine and ten degree, which included 2,9,2,1,1
      cases respectively. CONCLUSION: As a special powerful injure, FSI always
      companied with concurrent and multiple injure, and characterized by missed,
      incorrect and delayed diagnosis and infelicitous treatment, which lead to the
      high frequency and degree of injure. To prevent missed and incorrect forensic
      identification, we should have a full realization of the particularity of FSI,
      and evaluate the function of shoulder all-sidely, objectively and synseticaly.

PMID- 17190150
TI  - [Legal-medical analysis of 147 homicidal cases].
AB  - 147 homicidal cases were studied through case status, scene investigation, and
      postmortem examination. Its characters were then concluded for reference of
      detection in homicidal scene.

PMID- 17190151
TI  - [Assessment of criminal responsibility for perpetrators of homicide: analysis of
      105 cases].
AB  - OBJECTIVE: To explore the main factors that most influence the psychiatrists in
      the process of assessing the capacity for criminal for perpetrators of homicide.
      METHODS: 105 homicide cases were retrospectively analyzed. RESULTS: The number of
      cases for no responsibility, reduced responsibility and full responsibility is 41
      (39.0%), 28 (26.7%) and 36 (34.3%) respectively. The assessment of capability for
      criminal responsibility was significantly correlated with three major factors,
      they are: whether the homicide was driven by psychopathological factors (Gamma =
      0.906, P = 0.000), whether the perpetrator was suffering a severe mental
      disorders (Gamma = 0.761, P = 0.000) and, whether the victim is the perpetrator's
      family member or relative (Gamma = 0.412, P = 0.000). CONCLUSION: Forensic
      psychiatrists take three major aspects into account in their process in assessing
      capacity for criminal responsibility, in a descending order, they are: was the
      homicide driven by pathological motivation? Was the perpetrator suffering from a
      severe mental disorder? Was the victim a family member or stranger?

PMID- 17190152
TI  - [Application of contribute degree in forensic mental trauma assessments].
AB  - It is very difficult to identify the relationships between tangle events and
      accompanied mental disorders. There are often different descriptions of the same
      controversial conclusion. This thesis introduce the conception of contribute
      degree and discusses the causality of tangle events and accompanied mental
      disorders in forensic mental trauma assessments.

PMID- 17190153
TI  - [Study of Papaver somniferum cultivars identification by TD-RAPD technique].
AB  - OBJECTIVE: The feasibility of Papaver somniferum L. cultivars identification was
      explored by TD-RAPD technique. METHOD: Genomic DNA was extracted by improved CTAB
      method. One sample of species from Papaver somniferum L in xishuangbanna area.
      was studied by using TD-RAPD method. RESULT: We established an optimal method of
      extracting genomic DNA. Six primers were picked out from 10 primers. CONCLUSION:
      TD-RAPD could be applied to researches of molecular marker of Papaver somniferum
      L. TD-RAPD technique provide a method to constitute DNA database of Papaver
      somniferum L. and conclude the source of opium poppy.

PMID- 17190154
TI  - [Peripheral nerve injury and male sexual dysfunction].
AB  - The genital organ is innervated by autonomic and somatic nerve. The former is
      both sympathetic and parasympathetic nerve and the later is comprised by sensory
      and motor fibers. The symptoms of male sexual dysfunction are sexopathy, erectile
      dysfunction, disorder of ejaculation and orgasm, and pianism. Not only different
      symptom but the same symptom can be induced by different injured nerve. The
      relationship between peripheral nerve injury and male sexual dysfunction should
      be understood correctly.

PMID- 17190155
TI  - [Relationship between event-related potentials and brain injury].
AB  - Event-related potentials (ERPs) develop promptly as one kind of special evoked
      potentials. And it is one of the most effective methods to investigate human's
      cognition function in these years. P300 is the component of ERPs which is widely
      and maturately researched and has intimate relation with attention, memory and
      other high psychological activity. The evaluation of recognition change after
      brain injury is the focus of the research. With the development of relatively
      research, it is deemed that this technique has wide application perspective in
      many aspects such as forensic clinical medicine and forensic psychiatry.

PMID- 17190156
TI  - [The application of radiological imaging in the forensic pathology about cervical
      part].
AB  - Multislice spiral computed tomography (MSCT) and magnetic resonance imaging (MRI)
      are useful to analyze cervical injury. Especially in injury of skeleton and soft
      tissue, it has equal value with conventional autopsy. Even they can reparation
      some shortcoming consisted in the cervical part autopsy. In some difficult
      postmortem examination of decomposed, charred or highly infectious cadavers and
      in some religion country, they should be a useful alternative way to examine
      injury in cervical part of cadaver such as mechanical asphyxia, whiplash injury,
      vertebra injury, or vascular injury.

PMID- 17190157
TI  - [Research evolvement of postmortem diagnosis of early myocardial infarction in
      forensic pathology].
AB  - The cardiac sudden death occupies primacy among the cause of death in adult.
      Myocardial infarction is one of the main mechanisms of sudden death of coronary
      heart disease. Because of early myocardial infarction happened abruptly and might
      die in a short time, and the typical or special changes in morphology is absent,
      so it is the focus of medico legal research forensic fulfill all long. This paper
      reviewed the characters of myocardial infarction, applications and limits in
      forensic fields, and prospected feasibility of new clinical markers in forensic
      practice, and expected to enhance accuracy of postmortem diagnosis in MI.

PMID- 17190158
TI  - The case: Necrotizing fasciitis.

PMID- 17190160
TI  - Mobile-bearing total knee systems.

PMID- 17190159
TI  - Bilateral tibial tubercle avulsion fractures.

PMID- 17190161
TI  - The art of practicing spine surgery.

PMID- 17190162
TI  - Intramedullary stenting for femoral impaction grafting.

PMID- 17190163
TI  - The freeing of hands for open reduction and internal fixation.

PMID- 17190164
TI  - Disk regeneration.

PMID- 17190165
TI  - Computed tomography of musculoskeletal pathology.

PMID- 17190166
TI  - Concepts in crotaline snake envenomation management.

PMID- 17190167
TI  - Management of acute lateral side ligament injuries of the knee.

PMID- 17190168
TI  - Multidisciplinary management of orthopedic patients with sickle cell disease.
AB  - With pharmacological treatment, the lifespan of the patient with sickle cell
      disease can be extended to the sixth decade. Currently the only curative therapy
      for sickle cell disease is hemopoietic cell transplantation, which is still
      undergoing technical refinement. Most patients can be expected to undergo at
      least one orthopedic surgical procedure in their lifetime. Multidisciplinary
      management of orthopedic patients with sickle cell disease will decrease the
      overall complication rates and improve clinical outcomes.

PMID- 17190169
TI  - Computed tomographic evaluation of component position on dislocation after total
      hip arthroplasty.
AB  - True proper position after total hip arthroplasty was determined by measuring the
      cup and stem anteversion using computed tomography. We compared 20 dislocated
      hips (14 posterior and 6 anterior) with 18 non-dislocated hips. Both the cup
      anteversion and the stem anteversion showed no differences among the groups. The
      sum of cup and stem anteversion in posterior dislocated hips was significantly
      lesser than that in non-dislocated hips and the sum in anterior dislocated hips
      was significantly greater than that in non-dislocated hips. These results
      suggested even if the cup alone or the stemalone is at proper position,
      dislocation might occur.

PMID- 17190170
TI  - Use of trochanteric nail for proximal femoral extracapsular fractures.
AB  - Proximal femoral extracapsular fractures have shown a significantly high
      morbidity and mortality rate at 1 year in cases of nonoperative treatment. The
      standard gamma nail was originally designed to provide stable fixation and allow
      early mobilization and weight bearing for elderly patients. The design of the
      standard gamma nail, however, appears to be associated with intraoperative or
      postoperative femoral shaft fractures in < or = 17% of patients, compromising the
      outcome. The trochanteric nail was developed to overcome the problems encountered
      with the use of the standard gamma nail. Between July 2000 and January 2001, 88
      consecutive proximal femoral extracapsular fractures were treated with a
      trochanteric nail, Seventy-five patients (76 fractures) were observed clinically
      and radiographically for 2 years.

PMID- 17190171
TI  - Clinical values in computer-assisted total knee arthroplasty.
AB  - Thirty posterior stabilized total knee prostheses implanted using a computed
      tomography-free navigation system were compared to a control group of 30 matched
      total knee prostheses of the same type implanted via a classical, surgeon
      controlled technique. The accuracy of the implantations in relation to the
      mechanical axis in the navigation group was superior to that of the manual group.
      Early two-year clinical results including range of motion and Knee Society
      Clinical Rating Score were equally good compared to the manual group. However,
      potential long-term outcome and functional improvement require further
      investigation.

PMID- 17190172
TI  - Objective evaluation of shoulder pain by measuring skin impedance.
AB  - The subjective nature of pain has made its objective evaluation rather difficult.
      Recently, skin impedance was reported to reflect pain. The purpose of this study
      was to determine the usefulness of measuring skin impedance in evaluating
      shoulder pain. Fifty-three patients with shoulder pain were examined. Skin
      impedance was measured by a skin impedance meter in three different conditions
      and was compared with the visual analog scale recorded at the same time.

PMID- 17190173
TI  - Bilateral olecranon apophyseal nonunion in an adolescent boy.

PMID- 17190174
TI  - A "silent" fracture mimicking osteomyelitis.

PMID- 17190175
TI  - Late-onset infection of total knee arthroplasty caused by the Klebsiella
      pneumoniae bacteremia.

PMID- 17190176
TI  - The metabolic syndrome: is it really a syndrome?

PMID- 17190177
TI  - Induced hypothermia following out-of-hospital cardiac arrest; initial experience
      in a community hospital.
AB  - BACKGROUND: Successful resuscitation from sudden cardiac death is frequently
      accompanied by severe and often fatal neurologic injury. Induced hypothermia (IH)
      may attenuate the neurologic damage observed in patients after cardiac arrest.
      HYPOTHESIS: This study examined a population of nonselected patients presenting
      to a community hospital following successful resuscitation of sudden cardiac
      death. We sought to determine whether a program of induced hypothermia would
      improve the clinical outcome of these critically ill patients. METHODS: We
      initiated a protocol of IH at the Oklahoma Heart Hospital in August of 2003.
      Study patients were consecutive adults admitted following successful
      resuscitation of out-of-hospital cardiac arrest. Moderate hypothermia was induced
      by surface cooling and maintained for 24 to 36 h in the Intensive Care Unit with
      passive rewarming over 8 h. RESULTS: Forty-nine patients who were resuscitated
      and had the return of spontaneous circulation completed the hypothermia protocol.
      The cause of cardiac arrest was acute myocardial infarction in 24 patients and
      cardiac arrhythmias in 19 patients. Nineteen patients (39%) survived and were
      discharged. Sixteen of the patients discharged had no or minimal residual
      neurologic dysfunction and 3 patients had clinically significant residual
      neurologic injury. CONCLUSION: A program of induced hypothermia based in a
      community hospital is feasible, practical, and requires limited additional
      financial and nursing resources. Survival and neurologic recovery compare
      favorably with clinical trial outcomes.

PMID- 17190178
TI  - Stent implantation in variant angina refractory to medical treatment.
AB  - BACKGROUND: Vasospastic angina usually responds well to medical treatment.
      HYPOTHESIS: The present study describes our experience in patients who received a
      coronary stent because of recurrent variant angina refractory to medical
      treatment and evaluates stent implantation as an alternative treatment. MATERIALS
      AND METHODS: Between March 1998 and February 2005, recurrent variant angina was
      diagnosed in 22 patients admitted to our coronary care unit. Of these, five
      patients (22.7%), were refractory to pharmacologic treatment. Coronary
      angiography and coronary stents were indicated. Clinical follow-up was 29 +/- 6
      months. RESULTS: Stenting was performed during diagnostic coronary angiography in
      two patients. In the other three patients, the stent was implanted 24-48 h later.
      We observed coronary spasm recurrences proximal or distal to the stent in four
      patients-two during the stent implantation procedure and the other two in the
      coronary care unit within 48 h post angioplasty. Three patients where treated
      with additional stenting and the fourth patient improved with pharmacologic
      treatment. During follow-up three patients remained asymptomatic. The fourth
      patient had diffuse in-stent restenosis in the third month, and the fifth patient
      showed a de novo lesion in the treated segment 2 years later. CONCLUSIONS: Stent
      implantation in patients with recurrent variant angina refractory to medical
      treatment may be an alternative treatment in carefully selected, clinically
      unstable patients. Spasm recurrences may occur in other segments of the treated
      artery, probably due to the diffuse nature of the disease. Immediate and
      continued surveillance is recommended because of the risk of adverse clinical
      events.

PMID- 17190179
TI  - Control of rapid heart rate changes for electrocardiographic analysis:
      implications for thorough QT studies.
AB  - BACKGROUND: Following an abrupt change in heart rate (HR), QT adaptation is
      achieved within a delayed time frame. HYPOTHESIS: The exclusion of
      electrocardiograms (ECGs) showing rapid HR changes influences the level of a drug
      induced QT prolongation. METHODS: Continuous 12-lead ECG-Holter monitoring was
      performed in 31 healthy subjects. Using the "bin" method, we evaluated
      moxifloxacin effects on (1) QT interval duration at different RR intervals and
      (2) on the rate dependence of QT interval. These endpoints were calculated
      separately for five types of ECG analysis: classification of cardiac complexes
      based on (a) the single preceding RR interval (RR-1) and (b) RR filters excluding
      rapid HR changes according to the formula RR-1 = RR[time-window] +/- threshold,
      where the time-window could be 30 or 60 s (R30 and R60) and the threshold 15 or
      30 ms (th15 or th30). RESULTS: Moxifloxacin-induced QT prolongation was
      consistently higher using the stable models when compared with the RR-1 model.
      Moxifloxacin-induced QT prolongation at RR = 1000 ms was 8.2 +/- 11.2 vs. 10.9 +/
      10.4 ms using the RR-1 and R60th15 stable models, respectively (p < 0.05).
      Moxifloxacin-induced QT prolongation was more pronounced at slow than at fast HR.
      This so-called "reverse rate-dependent" effect was more pronounced when assessed
      using stable HR models (0.023 IC95% [0.019;0.027] vs. 0.015 IC95% [0.012;0.017]
      using the RR-1 model). CONCLUSION: The exclusion of ECGs with rapid HR changes
      influences the magnitude of drug-induced QT changes. The hysteresis phenomenon
      should not be neglected when dedicated QT studies are performed.

PMID- 17190180
TI  - The impact of time and day on the presentation of acute coronary syndromes.
AB  - BACKGROUND: The frequency of acute myocardial infarction (AMI) peaks on Mondays
      and in the mornings. However, the distribution of the types of acute coronary
      syndromes (ACS), including unstable angina (UA), has not been systematically
      evaluated. HYPOTHESIS: The distribution of the types of ACS and clinical
      presentations varies by time and day of admission. METHODS: A retrospective
      cohort study was conducted in 1,946 consecutive nontransfer ACS admissions (1999
      2004) to a tertiary-care academic center to assess presenting clinical variables
      in patients admitted on days versus nights (6 P.M.-6 A.M.) and weekdays versus
      weekends (Friday 6 P.M.-Monday 6 A.M.). RESULTS: There were fewer ACS admissions
      than expected on nights and weekends (p < 0.001), but the proportion of patients
      with ACS presenting with ST-elevation myocardial infarction (STEMI) is 64% higher
      on weekends (p < 0.001) and 31% higher on nights (p = 0.022). This increased
      proportion with STEMI results in a greater proportion of ACS with AMI on weekends
      (up arrow 10%, p = 0.006) and nights (up arrow 7%, p = 0.033). Using multivariate
      modeling, the increase in patients with AMI on weekends was not explained by
      conventional risk predictors. CONCLUSIONS: Although fewer patients with ACS
      presented on nights and weekends, patients at those times were more likely to
      have an AMI, driven largely by an increased proportion with STEMI at those times.
      Consideration should be given to these findings when developing clinical care
      paradigms, health care staffing needs, and when comparing new treatment outcomes
      in patients with ACS.

PMID- 17190182
TI  - Valentin Fuster.

PMID- 17190181
TI  - Extensive myocardial infarction and left ventricular thrombus after chest
      collision during a soccer match.

PMID- 17190183
TI  - Bone marrow stromal cells express neural phenotypes in vitro and migrate in brain
      after transplantation in vivo.
AB  - OBJECTIVE: To investigate the differentiation of bone marrow stromal cells (BMSC)
      into neuron-like cells and to explore their potential use for neural
      transplantation. METHODS: BMSC from rats and adult humans were cultured in serum
      containing media. Salvia miltiorrhiza was used to induce human BMSC (hBMSC) to
      differentiate. BMSC were identified with immunocytochemistry. Semi-quantitative
      RT-PCR was used to examine mRNA expression of neurofilamentl (NF1), nestin and
      neuron-specific enolase (NSE) in rat BMSC (rBMSC). Rat BMSC labelled by
      Hoschst33258 were transplanted into striatum of rats to trace migration and
      distribution. RESULTS: rBMSC expressed NSE, NF1 and nestin mRNA, and NF1 mRNA and
      expression was increased with induction of Salvia miltiorrhiza. A small number of
      hBMSC were stained by anti-nestin, anti-GFAP and anti-S100. Salvia miltiorrhiza
      could induce hBMSC to differentiate into neuron-like cells. Some differentiated
      neuron-like cells, that expressed NSE, beta-tubulin and NF-200, showed typical
      neuron morphology, but some neuron-like cells also expressed alpha smooth muscle
      protein, making their neuron identification complicated. rBMSC could migrate and
      adapted in the host brains after being transplanted. CONCLUSION: Bone marrow
      stromal cells could express phenotypes of neurons, and Salvia miltiorrhiza could
      induce hBMSC to differentiate into neuron-like cells. If BMSC could be converted
      into neurons instead of mesenchymal derivatives, they would be an abundant and
      accessible cellular source to treat a variety of neurological diseases.

PMID- 17190185
TI  - Molecular cloning of a novel cDNA from Mus muscular BALB/c mice encoding glycosyl
      hydrolase family 1: a homolog of human lactase-phlorizin hydrolase.
AB  - OBJECTIVE: To study the mechanism of lactose intolerance (LI) by cloning the
      mouse lactase cDNA and recombining a vector. METHODS Total murine RNA was
      isolated from the small intestine of a 4-week-old BALB/c mouse (d). Gene-specific
      primers were designed and synthesized according to the cDNA sequences of lactase
      phlorizin hydrolase (LPH) in human, rat, and rabbit. A coding sequence (CDS)
      fragment was obtained using RT-PCR, and inserted into a clone vector pNEB-193,
      then the cDNA was sequenced and analyzed using bioinformatics. RESULTS: The cDNA
      from the BALB/c mouse with 912 bp encoding 303 amino acid residues. Analysis of
      the deduced amino acid sequence using bioinformatics revealed that this cDNA
      shared extensive sequence homology with human LPH containing a conserved glycosyl
      hydrolase family 1 motif important for regulating lactase intolerance.
      CONCLUSION: BALB/c mouse LPH cDNA (GenBank accession No: AY751548) provides a
      necessary foundation for study of the biological function and regulatory
      mechanism of the lactose intolerance in mice.

PMID- 17190184
TI  - Risk factors for SARS-related deaths in 2003, Beijing.
AB  - OBJECTIVE: To study the potential risk factors for severe acute respiratory
      syndromes (SARS)-related deaths in Beijing. METHODS: Epidemiological data were
      collected among the confirmed SARS patients officially reported by Beijing
      Centers for Disease Control and Prevention (BCDC), and information was also
      supplemented by a follow-up case survey. Chi-square test and multivariate
      stepwise logistic regression analysis were performed. RESULTS: Old age (over 60
      years) was found to be significantly associated with SARS-related deaths in the
      univariate analysis. Also, history of contacting SARS patients within 2 weeks
      prior to the onset of illness, health occupation, and inferior hospital ranking
      as well as longer interval of clinic consulting (longer than 1 day) were the risk
      factors for SARS-related deaths. Multivariate stepwise logistic regression
      analysis found four risk factors for SARS-related deaths. CONCLUSION: Old age
      (over 60 years) is the major risk factor for SARS-related deaths. Moreover,
      hospital health workers, the designated hospitals for SARS clinical services and
      the interval of consulting doctors (less than 1 day) are protective factors for
      surviving from SARS.

PMID- 17190186
TI  - Immune responses to trichloroethylene and skin gene expression profiles in
      Sprague Dawley rats.
AB  - OBJECTIVE: To characterize the immune reaction in SD rats exposed to
      trichloroethylene (TCE) and to identify the gene expression profiles involved in
      skin after TCE exposure. METHODS: Fifteen percent of TCE was injected
      intradermally into the rat back (100 microL/120 g) at intervals of 7 days. Whole
      blood was collected 24 h after the fifth or seventh intradermic administration of
      TCE. The percentages of CD4+ and CD8+ of T lymphocytes were measured by a flow
      cytometer. The concentrations of IFN-gamma and IL-4 in the serum were semi
      quantified by ELISA. Total RNAs of skin samples at 3 h or 24 h after the seventh
      dose of TCE in SD rats were extracted, and gene expression profiles of these
      tissues were analyszed by rat toxicology U34 array of Affymetrix. RESULTS:
      Obvious decline of CD4+ in T lymphocytes was observed in the TCE-administer
      group. No significant concentration differences in IFN-gamma and IL-4 were found
      between TCE-treated and control rats. Gadd45a and Mel were significantly up
      regulated in skin tissue 24 h after TCE exposure. The expression regulation of
      immune response factors was as active as proteins associated with lipid
      metabolism and synthesis process in these skin samples of SD rats exposed to TCE.
      CONCLUSION: T-helper type 1 cells mediate immune response can not be elicited in
      TCE-treated SD rats, but certain immune disorder can be induced.

PMID- 17190187
TI  - Overweight and obesity-induced oxidative stress in children.
AB  - OBJECTIVE: To investigate whether overweight and obesity might cause oxidative
      stress and potential oxidative damage in overweight and obese children, and to
      explore its possible mechanism. METHODS: Eighty-five overweight and obese
      children (OOC), and eighty-five age-matched healthy children (HC) were recruited
      in this case-control study. The present study analyzed spectrophotometrically
      vitamin C (VC), vitamin E (VE), and 3-carotene (P-CAR) in plasma, as well as the
      activities of superoxide dismutase (SOD), catalase (CAT), and the level of
      malondialdehyde (MDA) in erythrocytes. RESULTS: Compared with those of VC, VE, P
      CAR, SOD, CAT and MDA in the HC group, the average values of VC, VE, 3-CAR, SOD,
      and CAT in the OOC group were significantly decreased (P<0.001), while the
      average value of MDA in the OOC group was significantly increased (P<0.001). The
      regression analysis demonstrated that VC, VE, P-CAR, SOD, and CAT were negatively
      correlated (P<0.05-0.01), and MDA was positively correlated with BMI (P<0.05).
      Fitting to the model of multiple stepwise regression of BMI on VC, VE, P-CAR,
      SOD, CAT, and MDA in 85 OOC was Y= 27.0041 + 0.2541MDA - 2.1448beta-CAR -
      0.0090CAT, where F= 43.8088, P<0.001, r = 0.7866, r(2)= 0.6187, adjusted r(2)=
      0.6046. The findings from the reliability analysis for VC, VE, P-CAR, SOD, CAT,
      and MDA used to reflect increased oxidative stress and potential oxidative damage
      in the OOC showed that the reliability coefficients (alpha, 6 items) = 0.7231,
      P<0.0001, and that the standardized item alpha = 0.9207, P<0.0001. CONCLUSION:
      The present study suggests that there exists an increased oxidative stress in
      overweight and obese children.

PMID- 17190188
TI  - Reduction of precursors of chlorination by-products in drinking water using
      fluidized-bed biofilm reactor at low temperature.
AB  - OBJECTIVE: To investigate the reduction of chlorination by-products (CBPs)
      precursors using the fluidized-bed biofilm reactor (FBBR). METHODS: Reduction of
      total organic carbon (TOC), ultraviolet absorbance (UV254), trihalomethane (THM)
      formation potential (THMFP), haloacetic acid (HAA) formation potential (HAAFP),
      and ammonia in FBBR were evaluated in detail. Results The reduction of TOC or
      UV254 was low, on average 12.6% and 4.7%, respectively, while the reduction of
      THMFP and HAAFP was significant. The reduction of ammonia was 30%-40% even below
      3 degrees C, however, it could quickly rise to over 50% above 3degrees C.
      Conclusions The FBBR effectively reduces CBPs and ammonia in drinking water even
      at low temperature and seems to be a very promising and competitive drinking
      water reactor for polluted surface source waters, especially in China.

PMID- 17190189
TI  - In vitro potentiation of antimalarial activities by daphnetin derivatives against
      Plasmodium falciparum.
AB  - OBJECTIVE: To screen the antimalarial compounds of daphnetin derivatives against
      Plasmodium falciparum in vitro. METHOD: Plasmodium faciparum (FCC1) was cultured
      in vitro by a modified method of Trager and Jensen. Antimalarial compounds were
      screened by microscopy-based assay and microfluorimetric method. RESULTS: DA79
      and DA78 showed potent antimalarial activity against Plasmodium falciparum
      cultured in vitro. CONCLUSION: Though the relationship between the structures of
      daphnetin derivatives and their antimalarial activities has not been clarified
      yet, this study may provide a new direction for discovery of more potential
      antimalarial compounds.

PMID- 17190190
TI  - Application of PCR-DGGE in research of bacterial diversity in drinking water.
AB  - OBJECTIVE: To analyze the structure of bacteria in drinking water by molecular
      biological techniques. METHODS: DNA of bacteria in drinking water was directly
      extracted without culture. 16S ribosomal DNA fragments, including V-6, -7, and -8
      regions, were amplified with universal primers (EUBf933GC and EUBr1387) and
      analyzed by DGGE. RESULTS: DGGE indicated that amplification products could be
      separated. The results showed that DGGE could be used in the separation of
      different microbial 16SrRNA genes extracted from drinking water. Though there
      were special bacteria in different water samples, the predominant bacteria were
      essentially the same. Three sequences of the reclaimed specific bands were
      obtained, and phylogenetic tree of these bands was made. CONCLUSION: Bacterial
      diversity in drinking water is identified by molecular biological techniques.

PMID- 17190191
TI  - Combined effect of fluoride and arsenate on gene expression of osteoclast
      differentiation factor and osteoprotegerin.
AB  - OBJECTIVE: To study the combined effect of fluoride and arsenate on the
      expression of SD rat osteoblastic osteoclast differentiation factor (ODF) mRNA
      and osteoprotegerin (OPG) mRNA. METHODS: Osteoblasts were obtained by enzymatic
      isolation from newborn SD rats. A factorial experiment was performed. Osteoblasts
      were exposed to NaF (0.5 mmolF/L, 4 molF/L) and Na3AsH2 (12.5 micromolAs/L and
      200 micromolAs/L) separately or F plus As and cultured for 48 h. The gene
      expression of osteoblastic ODF and OPG was observed by RT-PCR. RESULTS: The
      expression of ODF mRNA increased in F0.5, F4 groups compared with control group
      and two groups of F0.5As200, F4As200 compared with As200 group, and decreased
      significantly in groups of F4Asl2.5, F0.5As200, and F4AS200. The expression of
      OPG mRNA decreased in groups of F4, As200, F4As12.5, F0.5AS200, and F4AS200.
      CONCLUSION: The joint effect of fluoride and arsenate on the gene expression of
      ODF is antagonistic, while the combined effect on the gene expression of OPG is
      synergistic. F4, F4As12.5, and F0.5As200 promote bone resorption of rat
      osteoclasts, whereas F0.5As12.5 inhibits osteolytic effect of rat osteoclasts.

PMID- 17190192
TI  - Sampling survey of disability in 0-6 year-old children in China.
AB  - OBJECTIVE: To investigate the current status of disabled children and prevalence
      of disabilities in children aged 0-6 years and their risk factors, and to provide
      scientific evidence for making relevant policies for disabled children. METHODS:
      In a community-based cross-sectional study, multi-phase, stratified, unequal
      proportional and cluster sampling was adopted to survey 60 124 children aged 0-6
      years. All the investigated children were screened for disabilities, and those
      with positive screening tests were further diagnosed by various specialties.
      RESULTS: A total of 819 children were diagnosed as disabled with an overall
      prevalence of 1.362%, 0.155% for hearing disability, 0.160% for visual
      disability, 0.931% for intelligent disability, 0.424% for limb disability, and
      0.101% for mental disability. Prevalence of disability in children was higher in
      rural areas, and in families with two or more children, low educational level or
      in divorced families. CONCLUSION: The prevalence of disability can be reduced by
      economic development, improvement of health care and quality of population, as
      well as harmonious familial relationship, early prevention of disability, and
      preschool education for disabled children.

PMID- 17190193
TI  - Mechanism of ascorbic acid-induced reversion against malignant phenotype in human
      gastric cancer cells.
AB  - OBJECTIVE: To find out the mechanisms of redifferentiation and reversion of
      malignant human gastric cancer cells induced by ascorbic acid. METHODS: Human
      gastric cancer cells grown in the laboratory were used. The Trypan blue dye
      exclusion method was used to determine the cell doubling time. The
      electrophoresis rate and colonogenic potential were the indices used to measure
      the rate of redifferentiation. The content of malondialdehyde (MDA) was measured
      using the thiobarbituric acid (TBA) method. The activities of superoxide
      dismutase (SOD), catalase (CAT) and the content of H202 were evaluated by
      spectrophotography. RESULTS: Six mmol/L ascorbic acid was used as a positive
      control. Human gastric cancer cells were treated with 75 microm hydrogen
      peroxide, which alleviated many of the malignant characteristics. For example,
      the cell surface charge obviously decreased and the electrophoresis rate dropped
      from 2.21 to 1.10 microm x s(-1) x V(-1) x cm(-1). The colonogenic potential, a
      measure of cell differentiation, decreased 90.2%. After treatment with ascorbic
      acid, there was a concentration- and time-dependent increase in hydrogen peroxide
      (H202) and the activity of superoxide dismutase (SOD). However, the activity of
      catalase (CAT) resulted in a concentration- and time-dependent decrease. SOD and
      3-amino-1,2,4-triazole (AT) exhibited some effects, but there were statistically
      significant differences between the SOD and AT group and the H202 group.
      CONCLUSIONS: Ascorbic acid induces growth inhibition and redifferentiation of
      human gastric cancer cells through the production of hydrogen peroxide.

PMID- 17190194
TI  - Molecular cloning and preliminary analysis of a fragile site associated gene.
AB  - OBJECTIVE: To analyze the molecular coining of a fragile site-associated gene.
      METHODS: Genomic Chinese hamster ovary (CHO) DNA library was constructed using
      high molecular weight CHO DNA partially digested with MboI restriction enzyme
      from cultured CHO cells. Screening of genomic DNA library followed the
      established procedures. Genomic CHO in the positive clones was sequenced.
      Appropriate primers were designed for the reverse transcriptase-polymerase chain
      reactions (RT-PCR). The RT-PCR products were cloned into a pCRII TOPO vector and
      confirmed by DNA sequencing. Antibodies were prepared using synthetic peptides as
      antigens by immunizing the rabbits. Immunohistochemical analyses were performed
      to evaluate the expression of the novel gene in different tissues. RESULTS: To
      investigate the molecular mechanism underlying the initial events of mdr1a
      amplification, we cloned 1q31 fragile site DNA. Strikingly, we found that this
      fragile site contained a novel gene which was designated as a fragile site
      associated (FSA) gene. FSA encoded an unusually large mRNA of approximately16 kb.
      Full-length human FSA cDNA was cloned. FSA mRNA was expressed in many cultured
      cells and tissue types. Immunohistochemical analyses also revealed an expression
      pattern of the encoded proteins in postmitotic, well-differentiated epithelial
      compartments of many organs, including colon, mammary glands, ovary, prostate,
      and bladder. CONCLUSION: FSA plays an important role in regulating mammalian
      epithelial cell growth and differentiation.

PMID- 17190195
TI  - Effects of iron and phosphorus on Microcystis physiological reactions.
AB  - OBJECTIVE: To observe the effects of iron and phosphorus on Microcystis
      physiological reactions. METHODS: The experimental conditions were chosen as the
      light dark cycles of 16 h 8 h, 12 h 12 h, and 8 h 16 h. The cell change of
      morphology and life history, cell number, cell color, and cell area of
      Microcystis were analyzed quantitatively. According to the resource competition
      and Monod equation, Microcystis kinetics of phosphorus and iron were also
      examined. RESULTS: The longer light time caused more special cell division,
      slower growth rate, and easier change of bigger cell area. The color of alga was
      changed from green to brown. Ks and micromax of phosphorus absorption were 0.0352
      mircomol x L(-l) and 0.493 d(-1), respectively. Those of iron absorption were
      0.00323 micromol x L(-1) and 0.483 d(-1). CONCLUSION: Microcystis bloom is more
      dominant than other algae.

PMID- 17190196
TI  - A prediction model of MF radiation in environmental assessment.
AB  - OBJECTIVE: To predict the impact of MF radiation on human health. METHODS: The
      vertical distribution of field intensity was estimated by analogism on the basis
      of measured values from simulation measurement. RESULTS: A kind of analogism on
      the basis of geometric proportion decay pattern is put forward in the essay. It
      showed that with increasing of height the field intensity increased according to
      geometric proportion law. CONCLUSION: This geometric proportion prediction model
      can be used to estimate the impact of MF radiation on inhabited environment, and
      can act as a reference pattern in predicting the environmental impact level of MF
      radiation.

PMID- 17190197
TI  - Detection of Panulirus argus Virus 1 (PaVI) in the Caribbean spiny lobster using
      fluorescence in situ hybridization (FISH).
AB  - Panulirus argus Virus 1 (PaV1) is the first virus known to be pathogenic to a
      wild lobster. It infects the Caribbean spiny lobster P. argus from the Florida
      Keys, and has a predilection for juveniles. The monitoring of the virus in wild
      populations and study of its behavior in the laboratory require the development
      of reliable diagnostic tools. A sensitive and specific fluorescence in situ
      hybridization (FISH) assay was developed for detection of PaV1. The lower
      detection limit using a 110 bp DNA probe in a dot-blot hygridization for PaV1 DNA
      was 10 pg of cloned template PaV1 DNA and 10 ng of genomic DNA extracted from the
      hemolymph of diseased spiny lobster. The fluorescein (FITC)-labeled probe
      specifically hybridized to PaVl-infected cells in the hepatopancreas, hindgut,
      gills, heart, foregut, and nerve tissues. FITC staining was observed around the
      inner periphery of the nuclear membrane, with lighter staining in a more
      dispersed pattern within the nucleus. The probe did not hybridize with host
      tissues of uninfected spiny lobsters, nor did it cross-react with 4 other virus
      samples tested. This assay will facilitate our understanding of the pathogenesis
      of the viral disease and help in monitoring efforts directed at determining the
      prevalence of PaV1 in juvenile nurseries for this lobster.

PMID- 17190198
TI  - Sub-clinical infection of farmed Atlantic salmon Salmo salar with salmonid
      alphavirus--a prospective longitudinal study.
AB  - A prospective longitudinal study of salmonid alphavirus infection in farmed
      Atlantic salmon Salmo salar L. was initiated in post-transfer smolts on a UK farm
      in July 2004 and continued for 320 d. Sampling was concentrated on a single caged
      population (C4) with serum and tissue samples collected and tested for viraemia,
      virus neutralising (VN) antibodies and viral nucleic acid by real time RT-PCR and
      by histopathology; 380 sera collected between Days 0 (DO) and 139 (D139) were
      consistently negative for both viraemia and VN antibodies. The first evidence of
      infection was detected on D146, when 4 out of 20 fish were found to be viraemic
      and 1 of 20 to be antibody-positive. On D153 only 2 of 20 fish was viraemic and 1
      antibody positive. At the next sampling (D158) no viraemic or antibody positive
      fish were detected. Thereafter, one or two viraemic fish were detected on 6
      occasions, including on D320. The prevalence of antibody-positive fish remained
      low (0 to 5%) until D192 after which time it rose irregularly to a peak of 57.9%
      on D320. Real time RT-PCR testing of sera was more sensitive than screening for
      viraemia, detecting a peak of 35 % positive on D153 before declining.
      Histological lesions diagnostic for pancreas disease (PD) were observed at D146
      and D153 only. In addition, mild cardiac and to a lesser extent brain lesions
      were frequently found after virus was detected, but not in earlier samples. No
      clinical signs or mortalities attributable to PD occurred throughout the study.
      This is the first detailed report of sub-clinical infection and highlights the
      usefulness of longitudinal surveys and the detection of virus and antibodies as
      diagnostic and epidemiological tools.

PMID- 17190199
TI  - Viral haemorrhagic septicaemia (VHS) outbreaks in Finnish rainbow trout farms.
AB  - In Finland, viral haemorrhagic septicaemia virus (VHSV) was diagnosed for the
      first time in 2000 from 4 rainbow trout farms in brackish water. Since then the
      infection has spread and, by the end of 2004, VHSV had been isolated from 24
      farms in 3 separate locations: 2 in the Baltic Sea and 1 in the Gulf of Finland.
      The pathogenicity of 3 of these isolates from 2 separate locations was analysed
      in infection experiments with rainbow trout fry. The cumulative mortalities
      induced by waterborne and intraperitoneal challenge were approximately 40 and 90
      %, respectively. Pair-wise comparisons of the G and NV gene regions of Finnish
      VHSV isolates collected between 2000 and 2004 revealed that all isolates were
      closely related, with 99.3 to 100% nucleotide identity, which suggests the same
      origin of infection. Phylogenetic analysis revealed that they were closely
      related to the old freshwater isolates from rainbow trout in Denmark and to one
      old marine isolate from cod in the Baltic Sea, and that they were located close
      to the presumed ancestral source. As the Finnish isolates induce lower mortality
      than freshwater VHSV isolates in infection experiments, they could represent an
      intermediate stage of marine isolates evolving towards pathogenicity in rainbow
      trout.

PMID- 17190200
TI  - Infectious haematopoietic necrosis epidemic (2001 to 2003) in farmed Atlantic
      salmon Salmo salar in British Columbia.
AB  - I investigated a recent infectious haematopoietic necrosis disease (IHN) epidemic
      in farmed Atlantic salmon Salmo salar in British Columbia (BC), Canada. All
      companies with infected farms (n = 36) participated in the study. Over 12 million
      Atlantic salmon on infected farms died or were culled during the epidemic with
      cumulative mortality on the farms averaging 58%. The first reported case of IHN
      occurred in August 2001 and the last outbreak in June 2003. Outbreaks on the
      farms lasted between 20 and 22 wk. Genetic sequencing by other researchers,
      revealed that 2 different IHN isolates contributed to this epidemic, one linked
      to all cases in 4 areas, the other associated with all cases in a fifth area.
      Spatial and temporal patterns of the farm outbreaks were examined to determine
      possible methods of spread between the farms. Evidence presented herein appears
      to show that farming practices themselves contributed significantly to the spread
      between farms both within and between areas. Natural waterborne transmission may
      have played a role in the spread of the virus between farms located in close
      proximity to each other. The data collected from this epidemic are compared with
      reports which examined the first reported epidemic in Atlantic salmon in BC (1992
      to 1996). Evidence is presented for the hypothesis that wild fish species may
      have been the source of introduction of the virus into the farmed Atlantic salmon
      population.

PMID- 17190201
TI  - Detection of DNAs homologous to betanodavirus genome RNAs in barfin flounder
      Verasper moseri and Japanese flounder Paralichthys olivaceus.
AB  - I investigated the presence of DNA homologous to genome RNA1 and RNA2 (RNA1 DNA
      and RNA2 DNA) of betanodaviruses - the causative agent of viral nervous necrosis
      (VNN) --in eggs, sperm, ovarian cavity fluid, larvae, and juveniles of barfin
      flounder Verasper moseri and larvae and juveniles of Japanese flounder
      Paralichthys olivaceus collected at 6 sites in Hokkaido, Japan, from 1994 to
      2001. RNA1 DNA and RNA2 DNA were detected by PCR in 13 and 33 % of barfin
      flounder samples and 0 and 69% of Japanese flounder samples, respectively. No
      infectious virus was detected by cell culture or by successive immunoblot against
      coat protein (genome RNA2 product) using an E-11 cell line, except for a virus
      present in 1 dead fish collected during an outbreak of VNN in 1995. Nucleotide
      sequence analysis showed that RNA1 DNA had a 82 to 96 % similarity to
      betanodavirus genome RNA1, and that RNA2 DNA had a 69 to 98 % similarity to RNA2.
      The detection rate of RNA2 DNA after intraperitoneal injection of betanodavirus
      strain HCF-1 into larvae and juveniles of the 2 flounder species was higher in
      samples from surviving fish than in the uninfected controls, whereas the
      detection rate of RNA1 DNA did not show a clear trend. Infectious virus was only
      detected in samples from fish that died subsequent to injection. Transfection
      assays of the viral genome RNAs into the barfin flounder cell line MK-1 and
      Japanese flounder cell lines H-1 and H-2 resulted in production of RNA2 DNA in
      all 3 cell lines. Quantitative measurement by ELISA revealed reverse
      transcriptase (RTase) activity. These results suggest that the DNA forms are
      produced and persist in the 2 flounder species as both clinical and subclinical
      infections, and do not lead to virion production.

PMID- 17190202
TI  - Evidence for widespread distribution of piscidin antimicrobial peptides in
      teleost fish.
AB  - Antimicrobial peptides (AMPs) are increasingly recognized as a critical component
      of the host's defense against infection. Several types of AMPs have been recently
      identified from mucosal tissues or immune cells of a number of teleosts. Among
      these are the piscidins, which are 22 residue, alpha-helical AMPs that were
      originally isolated from mast cells of hybrid striped bass Morone saxatilis male
      x Morone chrysops female. Using an antibody specific for the conserved N-terminal
      amino acid sequence of piscidin 1, we used immunohistochemistry to probe skin,
      gill, and gastrointestinal tract of 39 teleosts representing 7 different orders.
      Nine fish species were piscidin-positive, with all of these species being in the
      Perciformes, the largest and most evolutionarily advanced order of teleosts.
      Piscidin-positive cells were identified in species belonging to the families
      Moronidae, Serranidae, Sciaenidae, Siganidae and Belontidae. Immunopositive cells
      were usually most consistent with mast cells, although in some species, the
      granule appearance and tinctorial properties diverged somewhat from those of a
      typical piscine mast cell. In addition, rodlet cells were piscidin-positive in
      one member of the family Cichlidae; to our knowledge, it is the first time that a
      host-associated chemical biomarker has been identified in rodlet cells. Our data
      suggest that piscidins are present in many evolutionarily advanced teleosts.
      Piscidin-immunoreactive cells were most common at sites of pathogen entry,
      including the skin, gill and gastrointestinal tract. These results strongly
      suggest that piscidins are a widespread and important component of many fishes'
      defense against disease.

PMID- 17190203
TI  - Endohelminth fauna of the marsh frog Rana ridibunda from Lake Hazar, Turkey.
AB  - In this study, 236 marsh frogs Rana ridibunda collected from Lake Hazar (Elazig,
      Turkey) at 15 d intervals between March 2001 and February 2002 were examined for
      endohelminths; of these, 148 (62.71%) frogs were found to be infected with
      helminths. In total, 9 helminth species (3 trematodes, 5 nematodes and 1
      acanthocephalan) were identified. We observed Gorgoderina vitelliloba (prevalence
      2.97%) in the urinary bladder, Haematoloechus variegatus (4.66%) and Rhabdias
      bufonis (8.90%) in the lung, Pleurogenoides medians (1.69%), Oswaldocruzia
      filiformis (3.81 %) and Acanthocephalus ranae (26.27 %) in the small intestine,
      Neoxysomatium brevicaudatum (16.95%) and Cosmocercoides sp. (3.39%) in the large
      intestine, and Eustrongylides excisus (14.41%) in the body cavity and on,the
      stomach. No helminth was found in the spleen, kidney, gall bladder, liver, heart
      or muscle. Of the 9 helminth species identified, Acanthocephalus ranae (26.27 %)
      had the highest prevalence and abundance and Oswaldocruzia filiformis (8.33+/
      4.09) had the highest mean intensity.

PMID- 17190204
TI  - Acute and chronic effects of Cr(VI) on Hypsiboas pulchellus embryos and tadpoles.
AB  - In the last few years there has been great concern about declines in the
      abundance of several species of amphibians around the world. Among amphibians,
      anurans have a biphasic life cycle, with aquatic tadpoles and generally
      terrestrial adults, and they have an extremely permeable skin, making them
      excellent indicators of the health of the environment. A number of different
      causes have been suggested for the global decline of anurans, the pollution of
      their habitat by chemical stressors being considered one of the major factors.
      Among chemical stressors, heavy metals are known for their high toxicity at very
      low concentrations. This study assessed short- (96 h, 'acute') and long-term
      (1272 h, 'chronic') exposure to Cr(VI) at lethal (3 to 90 mg 1(-1)) and sublethal
      concentrations (0.001 to 12 mg 1(-1)) on Hypsiboaspulchellus (previously called
      Hyla pulchella; see Faivovich et al. 2005) tadpoles (Fam. Hylidae) from central
      eastern Argentina. Fertilized eggs collected from a clean pond near La Plata
      (Buenos Aires Province) were used for acute and chronic toxicity testing. Assays
      were done under controlled laboratory conditions. Results of chronic exposure
      were used to assess the effect of factors such as toxicant concentration and age
      of organisms at the beginning of exposure on the response variables (growth,
      development and survival until metamorphosis). Results indicated a higher
      sensitivity to Cr(VI) of individuals first exposed as tadpoles than those first
      exposed as embryos during acute and chronic exposure. Exposure to the highest
      sublethal concentrations (6 to 12 mg 1(-1)) of the toxicant showed early
      inhibitory effects on growth of all treated organisms compensated at longer
      exposure periods with an increase in the growth rate compared to the control
      groups.

PMID- 17190205
TI  - Temperature-dependent protection against Ichthyophthirius multifiliis following
      immunisation of rainbow trout using live theronts.
AB  - Rainbow trout Oncorhynchus mykiss Walbaum, 1792 fingerlings were vaccinated by
      intraperitoneal (i.p.) injection using live theronts of the skin parasitic
      ciliate Ichthyophthirius multifiliis Fouquet, 1876 at 2 temperatures (12 and 20
      degrees C), and protection against challenge infections was subsequently
      evaluated by bath exposure to live theronts. Vaccination conferred a relative
      protection (evaluated as the decrease in the number of established theronts) at
      12 degrees C and almost complete immunity at 20 degrees C. Significantly
      increased immobilisation titers (using plasma immobilisation of live theronts)
      were found in immunised fish at Week 2 and 4 post-vaccination. Lysozyme activity
      of plasma from vaccinated fish increased from Week 1 to 4. Both immobilisation
      titers and lysozyme activity were significantly higher at 20 degrees C. This
      study demonstrated that live theronts are good candidates for an antigen source
      for development of effective vaccines against white spot disease in this fish
      host, and further indicated that the protection of rainbow trout against I.
      multifiliis infection is highly temperature dependent and may be associated with
      both adaptive and innate response mechanisms.

PMID- 17190206
TI  - [Cadaver dissection: a lesson on topographic anatomy].

PMID- 17190207
TI  - [Dorsal onlay urethroplasty with foreskin mucosa free graft (Barbagli's
      technique): preliminary results of our case series].
AB  - OBJECTIVES: We evaluate the indication and results in the treatment of complex
      urethral stenosis by the Barbagli's technique. METHODS: We retrospectively review
      8 patients undergoing dorsal onlay urethroplasty with foreskin mucosa free graft.
      We analyze their preoperative characteristics. Mean stenosis length was 6.25 cm
      and the site was bulbar urethra in seven cases and penile in one. Mean
      preoperative flow was 8.78 ml/sec. We describe the technique and present our
      results. RESULTS: There are 87.5% of goods results (cure of the stenosis) with 22
      months of mean follow-up. Only one patient required a second operation (end to
      end anastomosis) with good outcome. CONCLUSIONS: The dorsal onlay urethroplasty
      with foreskin mucosa free graft is an effective technique in long and complex
      urethral stenosis, and we consider it the technique of first choice in view of
      our results.

PMID- 17190208
TI  - [The usefulness of virtual endoscopy and CT urography in the diagnosis of upper
      urinary tract tumors].
AB  - OBJECTIVES: Upper urinary tract (UUT) tumors are a relatively low incidence
      pathology which often represents a diagnostic challenge for the urologist,
      because several imaging tests are usually necessary to achieve the final
      diagnosis. Over the last years CT scan has suffered a notable development and
      nowadays, with the arrival of new image processing hardware and software, it is
      possible to detect small urothelial lesions and to perform 3-D urinary tract
      reconstruction and virtual endoscopic navigation. METHODS: Between January 2004
      and June 2005 we performed a total of 15 examinations in 15 patients for the
      study of asymptomatic hematuria of probable upper urinary tract origin. The
      technique included three phases to obtain images: basal phase, vascular phase and
      excretory phase. Processing and image analysis was performed by one radiologist.
      RESULTS: A total of 10 tumors were diagnosed, with pathological confirmation in
      all cases. We did not register any complication secondary to the technique, and
      all patients tolerated well the exam. CONCLUSIONS: The CT urography is a safe,
      well-tolerated, highly sensitive and efficient imaging test, very useful in the
      diagnosis of renal and UUT pathology. It may become the only imaging test
      performed in the study of asymptomatic hematuria and the test of choice for the
      study of urological tumoral pathology.

PMID- 17190209
TI  - [Paratesticular liposarcoma. Clinical and pathological study of three cases and
      review of the literature].
AB  - OBJECTIVES: Paratesticular liposarcomas are rare; most published cases are single
      cases. We report the clinical, histological and immunohistochemical
      characteristics of three cases of paratesticular liposarcomas. METHODS: We
      performed clinical, histological and immunohistochemical studies with expression
      of ki 67 and p 53 markers in three cases of tumors of the spermatic cord.
      RESULTS: Patient age ranged from 36 to 67 years, with a mean of 54 years. All
      tumors were big, multinodular and predominant histological type was well
      differentiated (2/3), being one case undifferentiated (1/3). All cases were
      treated by surgical excision; one of them had a relapse five years later (33%) as
      a low-grade undifferentiated liposarcoma. None of the patients have developed
      metastases after a long follow-up (10, 7, and 5 yr.). CONCLUSIONS: Paratesticular
      liposarcomas have favourable prognostic markers (histological type, low
      proliferation index Ki 67 and p 53). The evaluation of this masses should be
      based on imaging tests, but a biopsy is necessary to determine their nature both
      in the case of primary tumors and recurrences. Surgical treatment should include
      complete excision with free margins to avoid recurrences.

PMID- 17190210
TI  - [Clinical and laboratory tests characteristics in children with nephrolithiasis:
      case control study].
AB  - OBJECTIVES: To evaluate the clinical and laboratory findings in pediatric
      patients with urolithiasis in a case control study and to obtain variables
      predicting a low risk of having urolithiasis. METHODS: Retrospective analysis of
      24 cases of children with urolithiasis (age range 3 to 17 years old) admitted to
      the pediatric emergency room or the hospital ward. Clinical and laboratory
      information was obtained from the clinical charts and compared with a control
      group of 29 patients with history of abdominal pain admitted to the hospital.
      Binary logistic regression and recursive partitioning analysis were used to
      obtain variables predicting a low risk of having urolithiasis. RESULTS: There was
      no difference in age, gender, dysuria or nausea (p > 0. 2) between groups. A
      difference regarding the presence of fever (p = 0.007), haematuria (p = 0.001),
      costovertebral angle tenderness (p = 0.004), family history (p = 0.007) and
      abdominal pain lasting more than 48 hs (p = 0.04) was detected. After logistic
      regression and using recursive partitioning, the presence or history of fever,
      absence of gross haematuria and no family history of urolithiasis showed a 100%
      negative predictive value and sensitivity (95% CI 84.7 to 100 and 89.2 to 100
      respectively). CONCLUSIONS: Children with abdominal pain present a low risk of
      having urolithiasis if there is a history or presence of fever, absence of gross
      haematuria and a negative family history of urolithiasis in a first degree
      relative.

PMID- 17190211
TI  - [The use of the Stone Sweeper catheter for stone disease of the upper urinary
      tract].
AB  - OBJECTIVES: The treatment of patients with a great burden of stones is very
      difficult and often requires complex treatments including different kinds of
      surgery, associated in some cases with ureteral stents. METHODS: We present the
      case of a patient with complex renoureteral stone disease in whom we used the
      stone sweeper stent before SWL. The catheter is a 6.5 Fr radial expanding stent
      with small baskets, a special structure designed to extract small stones < 5mm.
      RESULTS: The placement and retrieval of bilateral stents were performed without
      complications, extracting several small stones inside the baskets. CONCLUSIONS:
      The Stone Sweeper stent may play an important role in the treatment of patients
      with great stone burden; by dilating the ureter and helping the passage of stones
      and capturing small residual fragments it may decrease the need of new
      treatments. Currently, more clinic and research tests with this stent are
      necessary to determine proper indications and associated complications.

PMID- 17190212
TI  - [Transperitoneal laparoscopic adrenalectomy: initial experience].
AB  - OBJECTIVES: Since the first published report in 1992, laparoscopic adrenalectomy
      has been widespread and it is now accepted as the standard treatment option in
      most of benign diseases of the adrenal gland. Aim of the present study is to
      describe our initial experience with laparoscopic adrenalectomy. METHODS: Between
      May 2001 and December 2005, 15 patients were submitted to laparoscopic
      adrenalectomy for benign diseases of the adrenal gland. We analyzed patients
      characteristics (sex, age, initial diagnosis), operative and perioperative
      results (operative time, blood loss, time to first oral intake) and
      complications. RESULTS: Mean operative time was 143 minutes. Blood loss was
      minimal. Mean hospital stay was 90 hours. There was no need for open conversion
      and complication rate was low. CONCLUSIONS: Laparoscopic surgery of the adrenal
      gland is a safe and effective option which offers quality of life benefits to the
      patients.

PMID- 17190213
TI  - [Bladder neurofibroma: case report and bibliographic review].
AB  - OBJECTIVE: The prevalence of the disease is 1/3000 newborns; it is more frequent
      in men than in women with a 3:1 ratio in all races. Genitourinary tract
      neurofibromas usually arise from the pelvic and bladder nerves, and the prostatic
      plexus. Bladder is the most frequently affected organ of the urinary tract;
      bladder neurofibromatosis may present as a diffuse infiltrative process or an
      isolated neurofibroma. Bladder neurofibromas arise from nervous ganglia of the
      bladder wall and stain positive for protein S-100 and type IV collagen with
      immunohistochemical techniques. METHODS: We performed a bibliographic review
      about urinary tract neurofibromas, and specifically of bladder neurofibroma. We
      report the case of a 45-year-old female consulting for voiding symptoms and
      recurrent urinary tract infections. Imaging tests showed a mass in the left
      lateral wall of the bladder and diffuse thickening of the bladder wall. The
      thickening of the bladder wall is the most characteristic finding in imaging
      tests, which may also be present in other diseases such as inflammatory
      pseudotumor and leiomyoma, so that final diagnosis should be achieved by
      pathologic study. RESULTS: The case is relevant for the absence of previous
      diagnosis of neurofibromatosis, being bladder involvement its clinical debut.
      This is why it was difficult to suspect the final diagnosis: the absence of other
      characteristic clinical manifestations of the disease. Transurethral resection of
      the tumor was performed and pathologic and immunohistochemical studies offered
      the final diagnosis. The patient was followed in the urology clinic and also sent
      to the internal medicine department to rule out other organs involvement of the
      disease. CONCLUSIONS: Neurofibromatosis is a rare systemic disease, and urinary
      tract involvement is rarer. Bladder is the most frequently involved organ in the
      urinary tract, generally as a diffuse infiltration or more rarely a solitary
      tumor. The final diagnosis is pathological and immunohistochemical. Treatment is
      usually conservative. The patient should be worked up to rule out other
      manifestations of the disease, and followed to evaluate the development of new
      lesions.

PMID- 17190214
TI  - [Metastatic Crohn's disease involving the penile foreskin].
AB  - OBJECTIVE: To describe the case of the patient with history of Crohn's disease
      presenting metastatic extension to the penile foreskin. METHODS: Circumcision was
      carried out and the skin was sent to the pathology department. RESULTS:
      Pathologic study of the specimen showed an ulcerated granuloma without caseum,
      typically associated with metastatic Crohn's disease. After one year of follow-up
      there is no evidence of recurrence. CONCLUSIONS: Crohn's disease is a disease of
      unknown origin, the main characteristic of which is the development of non
      necrotizing granulomas that may involved not only the gastrointestinal tract.
      When the extraintestinal involvement is not produced by continuity we call it
      metastatic disease. Such metastases may be found in the genitourinary tract, and
      other sites. This involvement may include lithiasis, amyloidosis, ... and the
      presence of lesions in the genital skin, as in our case.

PMID- 17190215
TI  - [Extratesticular intraescrotal neurofibroma: case report].
AB  - OBJECTIVES: We report a rare case of intrascrotal neurofibroma in an adult
      patient not affected by neurofibromatosis (NF1). METHODS: Clinical diagnosis of
      asymptomatic right scrotal lipoma and left symptomatic inguinal hernia carried
      the patient to the surgical treatment. After the first surgical step of left
      hernia repair, we proceeded to the excision by an inguinoscrotal approach of a
      voluminous whitish neoplastic mass occupying the whole left scrotum and not
      involving homolateral testis. RESULTS/CONCLUSIONS: The histopathologic diagnosis
      was of neurofibroma, a benign neoplasm of peripheral nerves which rarely occurs
      at genital level.

PMID- 17190216
TI  - [Bladder leiomyosarcoma. Case report].
AB  - OBJECTIVE: We report a new case of bladder leiomyosarcoma in a young female
      patient. We review its features and different treatment options. METHODS: The
      patient underwent neoadyuvant chemotherapy and surgical excision. RESULTS: A
      partial response was achieved with neoadyuvant chemotherapy and remains still
      alive 60 moths after radical cystectomy CONCLUSION: Despite the poor prognosis of
      this disease, multimodal treatment may improve results. Neoadyuvant chemotherapy
      and subsequent radical excision could be a good combination therapy for these
      aggressive tumors.

PMID- 17190217
TI  - [Giant right adrenal myelolipoma].
AB  - OBJECTIVE: Adrenal myelolipoma is a rare benign tumor, well limited, variable in
      size, composed of fatty and hematopoietic tissues, the finding of which is
      usually incidental. If they reach a big size they may produce the feeling of
      abdominal mass, pain, neighbour organs compression and acute intratumoral or
      retroperitoneal hemorrhage. METHODS: We report the case of a 57-year-old male
      admitted to the hospital with acute abdominal pain. CT scan with i.v. contrast
      and adrenal biopsy were performed. RESULTS: Radiological findings: 9 x 10 cm
      right adrenal mass, well defined, hypodense, with a small calcification in its
      posterior area. Pathologic findings: benign tumor, encapsulated, with a mixture
      of mature fatty tissue and hematopoietic cells. CONCLUSIONS: The presence of fat
      within an adrenal mass is essential for the diagnosis. Differential diagnosis
      should be done with all adrenal tumors with a fat component. When no radiological
      diagnosis is made, pathologic confirmation is necessary.

PMID- 17190218
TI  - [Papillary urothelial carcinoma of the urachus].
AB  - OBJECTIVE: Persistence of a patent urachus is a relatively rare occurrence;
      however; the persistence of urachal remnants is common. The pathologic lesions of
      the urachus include benign and malignant neoplasms. The majority of malignant
      urachal neoplasms are adenocarcinomas. METHODS AND RESULTS: We report a case of
      papillary urothelial carcinoma of urachus in a 73-year-old woman. The patient was
      treated with complete surgical extirpation and partial cystectomy. CONCLUSION:
      The recognition of urachal remnants as vestigial structures and pathologic
      lesions of the urachus is important.

PMID- 17190219
TI  - [Tubulovillous adenocarcinoma of the renal pelvis. Case report].
AB  - OBJECTIVE: To present a case of tubulovillous renal pelvis adenocarcinoma.
      METHODS/RESULTS: An 81 year-old patient presented at Emergency Department with
      sepsis. CT scan showed a staghorn calculus with signs suggestive of pyonefrosis.
      A nephrectomy was performed and pathological exam revealed tubulovillous renal
      pelvis adenocarcinoma. CONCLUSIONS: Renal pelvis adenocarcinoma is a rare
      disease. It is usually accompanied by chronic urinary infections, on inflammatory
      state and staghorn calculi. The best therapeutic option is nephrectomy and the
      prognosis is poor.

PMID- 17190220
TI  - [Renal carcinoma metastatic to the peritoneum. Case report].
AB  - OBJECTIVE: We describe the case of a young male presenting with non-specific
      abdominal symptoms on follow-up after radical nephrectomy for renal carcinoma
      leading to the finding of local recurrence and peritoneal metastases. A second
      exploratory laparotomy was carried out for tumor reduction, but it was followed
      by fast peritoneal recurrence. Despite the treatment with alpha interferon, three
      months later he developed multiple hepatic metastases. CONCLUSIONS: Peritoneal
      involvement by renal cell carcinoma is rare and implies a bad prognosis.

PMID- 17190221
TI  - [Retroperitoneal fibrosis in relation to use of analgesics, tramadol and
      paracetamol].

PMID- 17190222
TI  - [Vesico-ureteral reflux].

PMID- 17190223
TI  - [Urologic diseases].

PMID- 17190224
TI  - [Subcutaneous prepuce metastasis secondary to rectal adenocarcinoma].

PMID- 17190225
TI  - Conformal prostate brachytherapy guided by realtime dynamic dose calculations
      using permanent 125iodine implants: technical description and preliminary
      experience.
AB  - OBJECTIVE: Low dose rate (LDR) prostate brachytherapy (permanent 125I or 103Pd
      seeds) is an accepted treatment option for low risk prostate cancer patients.
      However, differences in prostate spatial location, volume and gland deformation
      between the images obtained during pre-planning and later on during the implant
      procedure prevent the pre-planned intended dose to be accurately delivered. We
      are reporting on a new technique based on interactive real-time dynamic intra
      operative dose calculation with avoidance of postimplant CT for final dosimetry.
      The reasons leading us to implementing this new technique are discussed and
      preliminary results reported. 47-78 years). For the real time intra-operative
      dosimetric analysis the following values were obtained: a median of 98% (90%
      100%) for V90, of 60% (22%-76%) for V150 and 24% (9%-34%) for V200. The median
      intro-operative D90 obtained was 16,817 cGy with a range of 13,743 to 19,553 cGy.
      The median dose point calculation to the rectum maximum was 12,936 cGy and for
      the maximum in urethra was 21,880 cGy. For the real-time dynamic planning, the
      acute GU grade 1&2 toxicity was reduced from 28% and 2 1% to 16% and 6%
      respectively. Acute urinary retention was seen in 2/63 or 3% requiring a
      temporary post-implant bladder catheter. In addition, a decrease in chronic GU
      grade 1-2 toxicity was also seen from 16% and 17% to 1 1% and 2% respectively. No
      change in GI toxicity pattern was noted. No severe grade 3-4 intra-operative
      complications were noted. CONCLUSION: Real-time intra-operative planning was
      successfully implemented in our center. It avoids the possible implant quality
      and dose delivery disadvantages of the standard post-implant CT-based dosimetry
      by improving the accuracy of seed placement on real time, which was translated in
      lower rates of acute and chronic GU morbidity. In addition, avoids the
      unnecessary time, effort and cost of post-implant CT-based dosimetry.

PMID- 17190226
TI  - The vertical dimension: the high-angle problem.
AB  - When the patient who has excessive anterior facial height desires treatment for
      the correction of a malocclusion, the dimension of the dentition should be
      respected. The clinician must adhere to the anterior, posterior, vertical, and
      lateral limits of each patient's dentition--providing the musculature is normal-
      when the treatment plan is formulated. The goals of esthetics, health and
      function, stability, and treatment in harmony with growth are as valid for the
      high-angle patient as they are for a patient with a more normal vertical
      dimension. The diagnostic decisions made for the high-angle patient should be
      predicated on nonexpansion of the mandibular arch. Mandibular incisors must be
      overly upright. In addition, a decision on the mandibular third molars must be
      made prior to anchorage preparation-because their relationship to the mandibular
      second molars is critical if anchorage is to be properly prepared. A discussion
      of these topics as well as an illustrative case report are presented in this
      article.

PMID- 17190227
TI  - A new approach in the treatment of skeletal open bite: vertically activated bite
      block.
AB  - This study examined the effects of the vertically activated bite block, a new
      appliance designed for maxillary molar intrusion in open bite malocclusion, on
      the dentofacial structures in 1 adolescent patient and 1 adult patient. The
      vertically activated bite block consists of 2 parts, the main block and an
      auxiliary segment. The auxilliary segment is separated bilaterally from the main
      block in the posterior region and connected bilaterally to the main block in the
      palatal region by open jackscrews. Closing the jackscrews moves the auxiliary
      segment toward the palate, thereby inducing molar intrusion. The present study
      achieved a reduction in open bite, using the VABB through: (1) active intrusion
      of the maxillary molars; (2) control of posterior vertical alveolar development
      and/or compensatory eruption of the mandibular molars; (3) stimulation of
      anterior vertical alveolar development by restriction of the tongue; and (4)
      anterior repositioning of mandible. Achieving these dentoalveolar and skeletal
      changes are required treatment objectives in cases of skeletal open bite. As a
      result of attaining these objectives, the open bite was eliminated in 1 early
      growth and 1 late growth patient by 14 mm and 6 mm, respectively.

PMID- 17190228
TI  - Heat generated by residual adhesive removal after debonding of brackets.
AB  - AIM: To measure the rise in temperature during mechanical removal of residual
      adhesive after debonding of brackets in vitro. METHODS: Different carbide burs on
      a high-speed handpiece were tested. Acrylic on the buccal surfaces of recently
      extracted human maxillary incisors was removed using 3 types of carbide burs (6-,
      12-, 40-fluted) with a varying number of windings relative to the long axis of
      the shaft. The temperature was measured using a thermocouple probe in the pulp
      chamber of the extracted teeth. RESULTS: The highest mean rise in temperature was
      measured using a 6-fluted bur (+9.4 degrees C, P < .001), followed by the 12
      fluted bur (+6.5 degrees C, P <.001). The lowest rise in temperature (+1.2
      degrees C, not significant) was seen with a 40-fluted bur. After 3 to 8 seconds
      of continuous grinding, the rise in temperature seems to slow down. CONCLUSION:
      The removal of residual adhesive after debonding is best performed with fine
      burs. If 6-fluted burs are used, a pause after 5 to 10 seconds of continuous
      grinding is recommended, especially in the mandibular anterior area.

PMID- 17190229
TI  - Status of lingual orthodontics.
AB  - The lingual appliance was developed simultaneously in 2 countries during the
      1970s. Although not fully recognized by the orthodontic mainstream, lingual
      treatment has steadily expanded, with increased numbers of lingual orthodontists
      and patients. This article reviews the development, advantages and disadvantages,
      bonding techniques, biomechanics, and treatment procedures of the lingual
      appliance. Currently, there are few contraindications for treatment with the
      lingual appliance. Cephalometric measurements do not reveal statistically
      significant differences in treatment results between labial and lingual
      treatment; however, more clinical trial studies are needed to compare the
      efficiency and outcome of lingual appliances with those of labial appliances.

PMID- 17190230
TI  - Influence of the facial pattern on ANB, AF-BF, and Wits appraisal.
AB  - AIM: To assess the correlation between Wits and AF-BF appraisals with the ANB
      angle, and verify the influence of the facial type on these appraisals. METHODS:
      Lateral cephalometric radiographs from 118 untreated individuals were separated
      into 3 groups according to the facial pattern (brachyfacial, mesofacial, and
      dolichofacial). The radiographs were digitized and submitted to ANB angle and
      Wits and AF-BF appraisals on computer software. All radiographs were retraced for
      intraobserver and interobserver error tests. RESULTS: The Student's t test
      demonstrated no statistically significant differences on the intraobserver's test
      (P > .05). There were statistically significant differences in the readings of
      Wits values of the 3 groups and for AF-BF values in the brachyfacial and
      mesofacial groups (P <.05). The multiple linear regression tests demonstrated
      high correlation between ANB and AF-BF for the 3 groups (r2, 0.768). The same
      result was found for ANB and Wits (r2, 0.624). CONCLUSION: Facial pattern does
      not have an influence on the correlation between ANB and AF-BF nor between ANB
      and Wits, but it does influence the measurements of ANB, AF-BF, and Wits.

PMID- 17190231
TI  - Diagnostic protocol in cases of congenitally missing maxillary lateral incisors.
AB  - Patients with congenitally missing maxillary lateral incisors may seek treatment
      from an orthodontist for several reasons; unpleasant smile, dental arch
      disharmony, and midline deviations are among the most frequent complaints.
      Orthodontists and prosthodontists have raised important questions about the
      esthetics, occlusion, periodontal health, and psychological conditions noted in
      these patients. The decision to open lateral incisor spaces for prosthetics or
      close spaces by mesial movement of the canines requires a careful diagnosis and
      comprehensive multidisciplinary treatment planning. The purpose of this article
      is to present a diagnostic protocol to assist in the decision-making process,
      while analyzing patients with absent maxillary lateral incisors. The basis for a
      sound diagnosis and an effective treatment plan resides in careful consideration
      of the facial and dental characteristics of each patient. All information
      gathered during the clinical examination should be added to data obtained with
      other diagnostic tools, such as cephalometric analysis and orthodontic waxups, to
      achieve the treatment option that best suits the patient's expectations.

PMID- 17190232
TI  - Indirect bonding technique.
AB  - Accurate bracket placement is the key for the successful treatment of an
      orthodontic case. With indirect bonding, not only is the bracket placement more
      accurate but this technique also significantly reduces chairtime. In this
      article, the author explains use of thermal glue in an indirect bonding
      technique. In cases of constricted arches, a modified rapid maxillary expander
      can be used along with indirect bonding to reduce overall treatment time.

PMID- 17190233
TI  - Psychosomatic norm in orthodontics: problems and approach.
AB  - The term "psychosomatic norm" is not commonly used directly or indirectly in
      orthodontic discussions. However, at times, this may be the most important factor
      affecting patient satisfaction with treatment outcome. Psychosomatic norm is a
      norm based on a subjective psychosocial assessment of what is the patient's norm.
      A norm that significantly differs from the clinician's somatic norm, which is
      based on objective anatomic assessment, may end in a dilemma of unexplainable and
      unpredictable dissatisfaction with the orthodontic treatment outcome if not
      properly handled by the orthodontist. This review article attempts to approach
      and solve this clinically problematic situation.

PMID- 17190234
TI  - Treatment of a Class II malocclusion with bilaterally impacted canines: a case
      report.
AB  - AIM: This article describes the treatment of a patient with a Class II
      malocclusion and bilaterally impacted canines using a Jasper jumper appliance. An
      unfavorable side effect of the appliance became a benefit as part of the
      treatment. METHODS: Treatment objectives were to erupt the impacted canines,
      expand the decreased intermolar width, and obtain a well-balanced profile, with a
      Class I occlusion. The widening effect of this appliance on the maxillary molars
      was expected to help increase the intermolar distance. RESULTS: Favorable changes
      were noted, both in the occlusion and in the profile. Class I canine and molar
      relationships with ideal overjet and overbite were achieved. Overbite and overjet
      were decreased by a combination of retrusion and extrusion of the maxillary
      incisors, and protrusion and intrusion of the mandibular incisors. The maxillary
      canines were erupted successfully, with healthy gingival tissue. The crossbite in
      the right posterior segment was corrected as a result of the increase in the
      intermolar distance. CONCLUSION: The results gained were primarily dentoalveolar,
      rather than skeletal. There has been an improvement in the occlusion and
      esthetics.

PMID- 17190235
TI  - Buccal uprighting of canines and premolars for improved smile esthetics and
      stability.

PMID- 17190236
TI  - Evidence-bolstered orthodontics.

PMID- 17190237
TI  - Iranian orthodontics on the world stage.

PMID- 17190238
TI  - Diastolic heart failure: fact or myth?

PMID- 17190239
TI  - Retrospective review of the medical records of cardiology hospital outpatient
      clinics with the aim of determining the therapeutic approach to patients
      suffering from high blood pressure and/or dyslipidemia.
AB  - "Retrospective Review of the Medical Records of Cardiology Hospital Outpatient
      Clinics with the Aim of Determining the Therapeutic Approach to Patients
      Suffering from High Blood Pressure and/or Dyslipidemia" is a pilot study
      conducted by the Epidemiology and Cardiovascular Prevention Working Group of the
      Portuguese Society of Cardiology, based on the idea that all patients suffering
      from high blood pressure and/or dyslipidemia should be treated according to the
      guidelines for the treatment of these pathologies. OBJECTIVE: The main aim was to
      obtain data on the therapeutic approaches to patients observed in cardiology
      hospital outpatient clinics with high blood pressure and/or dyslipidemia as well
      as other concomitant diseases, in order to plan future wider-ranging studies and
      to analyze the main risk factors of cardiovascular conditions in this population.
      METHODS: Patients of both sexes aged 35 years or over were included, diagnosed at
      least one year previously with high blood pressure and/or dyslipidemia and
      observed on a regular basis at outpatient clinics, with data being recorded from
      the consultation after the start of the survey and from consultations in the
      previous 12 to 18 months. RESULTS: The survey covered 22 centers, and included
      285 patients, 58.4% male and 41.6% female. Of these patients, 87.7% had high
      blood pressure, 75.8% had dyslipidemia and 63.5 % had both pathologies; the
      prevalence of diabetes was high and that of coronary disease was very high. The
      mean body mass index (BMI) at the first observation was 28.7 +/- 4.4, while under
      20% of the patients had normal BMI. Sixty-two patients were ex-smokers, and 24
      still smoked. Mean systolic blood pressure (BP) was over 140 mmHg in all cases,
      and diastolic BP was around 80 mmHg. Mean LDL cholesterol remained at around 130
      mg/dl and HDL cholesterol at around 50 mg/dl. Almost all patients were under
      combined therapy with diuretics, beta-blockers, angiotensin-converting enzyme
      inhibitors, calcium channel blockers and statins, with most of these drug classes
      being prescribed with increasing frequency. CONCLUSION: Although this was a high
      risk population for cardiovascular conditions, control of blood pressure and of
      total and LDL cholesterol was in many cases inadequate, exceeding the values
      recommended in guidelines. Patients were usually polymedicated, with most drug
      classes, especially statins, being prescribed with increasing frequency.

PMID- 17190240
TI  - Carvedilol's actions are largely mediated by endogenous nitric oxide.
AB  - Carvedilol's adrenergic antagonism does not fully explain its therapeutic
      actions. We therefore tested the hypothesis that its action is associated with an
      increase in NO synthesis. Wistar rats (male, 9 weeks, n = 10) anesthetized with
      sodium pentobarbital were used. Arterial NO concentration ([NO]), determined by
      chemiluminescence, and mean arterial pressure (MAP) were monitored throughout the
      experiment. In protocol 1), the effects of carvedilol (1 mg/kg, iv) were studied
      over a eriod of 90 min. In protocol 2), carvedilol was p administered, followed
      by the NO synthase (NOS) inhibitor L-NAME (5 mg/kg, iv) and by a second
      carvedilol administration. In protocol 1), carvedilol induced a significant fall
      in MAP (from 125,0 +/- 4,5 mmHg to 78.2 +/- 2.6 mmHg; p <0.001), reaching a
      minimum at t = 11.7 +/- 2.1 min and recovering 60 min afterwards (105.7 +/- 5.9
      mmHg). Plasma [NO] varied in response to carvedilol in inverse proportion to MAP:
      baseline, 19.8 +/- 0.9 microM; t = 11.7 +/- 2.1 min, 32,3 +/- 2,3 microM; t = 60
      min, 17.3 +/- 1.9 microM. In protocol 2), L-NAME administration blocked the
      effects of carvedilol (L-NAME: MAP, 129.9 +/- 5.0 mmHg; [NO], 13,1 +/- 2,3
      microM. Post-L-NAME carvedilol administration resulted in MAP of 108.3 +/- 8.0
      mmHg, NS, and [NO], 21.3 +/- 1.3 microM, NS. These results suggest that
      carvedilol increases plasma [NO], which is associated with a fall in MAP.
      Furthermore, carvedilol's hemodynamic action was blocked by NOS inhibition,
      suggesting that it depends on endogenous NO production, thus possibly explaining
      carvedilol's effects in hypertension and in cardiac failure.

PMID- 17190241
TI  - Massive calcification of the mitral valve annulus in an adolescent with Marfan
      syndrome. A case report.
AB  - Marfan syndrome (MFS) is an inherited connective tissue disorder, transmitted as
      an autosomal dominant trait. Its phenotypic and clinical expression is variable
      and involves several body systems. The ocular, skeletal and cardiovascular
      systems are characteristically affected. Involvement of the cardiovascular system
      is the main cause of morbidity and mortality. The authors report the case of a
      thirteen-year-old girl, with MFS diagnosed at age five, referred to the pediatric
      cardiology department because of mitral regurgitation. In addition to severe
      mitral regurgitation due to prolapse of both mitral valve leaflets, diagnostic
      exams showed massive mitral annulus calcification and ostium secundum atrial
      septal defect (ASD). The patient underwent successful mitral valve repair and ASD
      closure surgery. In this report we highlight some features of MFS, stressing the
      cardiovascular aspects.

PMID- 17190242
TI  - Cardiac syndrome X.
AB  - This article describes: 1) situations that can cause angina pectoris in the
      absence of formal atherosclerotic obstructive lesions: a) those that cause non
      atherosclerotic coronary obstructions and b) those with normal coronary
      angiography, among them cardiac syndrome X (CSX); 2) the various definitions of
      CSX, particularly the definition of true CSX by Bertrand et al.: effort anginal
      pain plus positive exercise test, plus a second demonstration of myocardial
      ischemia (e.g. abnormal myocardial scintigraphy), plus normal coronary
      angiography; 3) the different pathogenic mechanisms that have been proposed for
      CSX, which suggest that the problem is mainly at the microvascular level; 4) the
      excellent survival prognosis of CSX; 5) the lack of any standard therapeutic
      protocol.

PMID- 17190243
TI  - Anomalous origin of the left coronary artery from the main pulmonary artery in a
      48-year-old woman.

PMID- 17190244
TI  - [Prevalence of arterial hypertension among 13-year old adolescents in the City of
      Porto].

PMID- 17190245
TI  - [Swollen knee: look in the pants for a cue].

PMID- 17190246
TI  - [500,000 cases per year in Germany. There is now a vaccine for control of
      rotavirus infection].

PMID- 17190247
TI  - [Asbestos and sequelae. Noli me tangere].

PMID- 17190248
TI  - [Diabetes and coronary heart disease frequently appear together. New guidelines
      regulate therapy and prevention].

PMID- 17190250
TI  - [Diabetes manifestation. Should they be prevented with drugs?].

PMID- 17190249
TI  - [Diabetic patients with heart disease. Especially strict blood values are
      important here].

PMID- 17190252
TI  - [Physical therapy--corset--operation. How can crooked backs be stretched?].

PMID- 17190251
TI  - [DREAM Study for prevention of diabetes. What conclusions may we draw?].

PMID- 17190253
TI  - [Rare food allergies. Exotic cooking with risks].

PMID- 17190254
TI  - [When children have headaches. First aid: clearing the leisure activities
      calendar].

PMID- 17190255
TI  - [Bird flu: increased resistance to oseltamivir. Are our weapons already blunt?
      (interview by Dr. Elke Oberhofer)].

PMID- 17190256
TI  - [Ascites and leg edema in an alcoholic. The liver as erroneous suspect].

PMID- 17190257
TI  - [When tattoos become bothersome or piercings a threat to health. From body
      jewelery to stigma].

PMID- 17190258
TI  - [Tattoos and permanent make-up: background and complications].
AB  - Tattoos and permanent make-up have enjoyed great popularity during recent years.
      However, a careful consideration of the risks is made only rarely before each
      procedure. Above all the undefined pigment compositions create unforeseeable
      health and appearance problems. The family physician should be familiar with the
      techniques, materials, as well as the possible risks of tattoos and permanent
      make-up when advising patients. Medical complications include, among other
      things, infections, allergies, keloid and granuloma formation.

PMID- 17190259
TI  - [Laser therapy for tattoos].
AB  - Tattoos are produced by bringing colorants of various compositions into the skin.
      The ingredients of these colorants are not declared and are not subjected to
      pharmacological and toxicological tests. Ultrashort and high intensity laser
      pulses are used to remove tattoos. The laser beam breaks up the pigments embedded
      in the skin so that they can be transported away from the site. Clinically, the
      pigment becomes less intense or completely disappears. The success of the laser
      treatment essentially depends on the pigments used in the tattoo and on how
      deeply the pigments are embedded in the skin. The laser treatment is slightly
      painful and has a low rate of permanent side effects.

PMID- 17190260
TI  - [Piercing complications in the facial area].
AB  - From the ENT specialist's view, the wearing of piercing jewelry on the outer ear,
      the tongue, the lips, the nose or the eyebrows is the cause of many and sometimes
      serious local and also systemic complications. Especially on the outer ear
      allergic reactions, keloid formation, traumatic tears or embedding of the piece
      of jewelry can occur in addition to simple, superficial infections or
      perichondritis. Through specific advice, early detection and treatment of
      complications, serious health damage to the wearer of piercing jewelry can be
      avoided.

PMID- 17190261
TI  - [Prevalence and characterization of the restless legs syndrome in the offices of
      German GPs].

PMID- 17190262
TI  - [Seventy-seven-year old patient with Recklinghausen's disease
      (neurofibromatosis)].
AB  - In this article, the case of a 77-year old patient who went to his physician
      complaining of increasing dizziness, unsteady gait and backaches is described.
      During the physical examination, a monstrous skin tumor was found on the back of
      the patient. MRI showed cerebellopontine angle tumors in the area of the
      trigeminal nerve and the beginnings of hydrocephalus. A diagnosis of
      neurofibromatosis type 1 was made on this basis. This disease, which is also
      called Recklinghausen's disease, belongs to a group of diseases called
      phakomatosis. It can develop due to the inheritance of an autosomal dominant
      trait, but can also arise through new mutations. Treatment varies with the
      symptoms. In the present case, the tumor was surgically removed without
      complications.

PMID- 17190263
TI  - [The 10-minute consultation. Benign paroxysmal positional vertigo].

PMID- 17190264
TI  - [Emergency checklist: erysipelas].

PMID- 17190265
TI  - [New subgroup analysis of the PROactive Study. Risk for recurrent stroke cut in
      half].

PMID- 17190266
TI  - [Interview with Prof. Erland Erdmann, Cologne. Oral antidiabetic with protective
      effect].

PMID- 17190267
TI  - [Health care funds, new risk structure adjustment, new fee legislation. Not
      implemented until 2009--if at all].

PMID- 17190268
TI  - [No concern about quality management! Compliance is very simple].

PMID- 17190269
TI  - Mechanisms of actions of sodium hypochlorite in cleaning and disinfection
      processes.
AB  - Sodium hypochlorite (NaOCl) is the most widely used disinfectant in the food
      industry despite the increasing availability of other disinfectants. Sodium
      hypochlorite fulfills many requirements as the ideal disinfectant and furthermore
      it has an excellent cleaning action. The effectiveness of sodium hypochlorite in
      the cleaning and disinfection processes depends on the concentration of available
      chlorine and the pH of the solution. Hypochlorous acid (HOCl) is a weak acid and
      dissociates to the hypochlorite ion (-OCl) and proton (H+) depending on the
      solution pH. It is generally believed that HOCl is the active species in the
      germicidal action, whereas the concentration of -OCl is a key factor determining
      the cleaning efficiency. This implies that the optimal pH region of the
      germicidal activity of sodium hypochlorite differs from that of its cleaning
      activity. This paper describes the theory and practice of the cleaning and
      disinfecting operations based on the use of sodium hypochlorite solution.

PMID- 17190270
TI  - Lethality of shock pressures to a marine Vibrio sp. isolated from a ship's
      ballast water.
AB  - The lethal effects of shock pressure treatment on suspended Vibrio sp. cells were
      examined. Lethality of shock pressures to the Vibrio sp. cells increased with the
      increase in the values of maximum shock pressures generated in the cell
      suspension. When the value was around 114 MPa, the total number of colony-forming
      cells was reduced from 10(8.5+/-0.1) colony-forming units (CFU) to 10(3.3) -
      10(3.4) CFU/ml, and complete loss of colony-forming ability was seen at the
      maximum value of 282 MPa. Almost all the cells could survive after the exposure
      to shock pressures including the maximum value of around 189 MPa in the presence
      of 2% sodium ascorbate (VitC-Na), whereas the total number of colony-forming
      cells was reduced to 10(1.6)-10(2.1) CFU/ml in the absence of VitC-Na. The
      surviving cells, however, showed sensitivity to 0.8% sodium cholate, a strong
      detergent. About 11% of cell-associated proteins had leaked out when the cells
      were exposed to lethal shock pressures including the maximum value of around 290
      MPa in the absence of VitC-Na. These results indicate that the radicals generated
      in the cell suspension may be closely related to the loss of colony-forming
      ability of the Vibrio sp. cells. Damage to the outer membrane structure also
      seems to have occurred by the exposure to shock pressures.

PMID- 17190271
TI  - Role of a surfactant in caustic alkali cleaning of polyethylene terephthalate
      surfaces fouled with organic substances.
AB  - The role of polyoxyethylene lauryl ether (POELE), a nonionic surfactant, in
      removing bovine serum albumin (BSA) and catechin from polyethylene terephthalate
      (PET) particles was quantitatively studied. Relatively large fractions of
      adsorbed BSA and catechin were removed from PET particles under weak alkaline
      conditions below pH 9, whereas cleaning with high concentrations of NaOH was not
      so effective, especially on the removal of BSA. This was attributed to the lower
      susceptibility of PET particles to water-based alkali (OH-) cleaning because of
      the lower degree of the polarity of PET surfaces. The combined use of NaOH
      solutions of moderate pHs and POELE could successfully improve the efficiency of
      cleaning of PET particles without a significant dissolution of PET materials.
      There was a good correlation between the lowered surface tension (7) of the NaOH
      solution with POELE and the removal efficiency of BSA or catechin. No effect of
      POELE was observed on the NaOH cleaning of hydrophilic alumina (A12O3) particles
      fouled with BSA. It could be concluded that the role of POELE in NaOH cleaning of
      PET particles was to lower the gamma of the NaOH solution and hence to facilitate
      penetration of OH- ions into the PET-BSA and PET-catechin interfaces.

PMID- 17190272
TI  - Development of a separate tank with an electrolysis-dependent bacteria
      controlling system for the long term storage of potable water.
AB  - For the long term storage of tap water, we developed a separate type of tank (5
      m3) equipped with an electrolysis system to control bacterial growth. The
      electrolysis conditions using 20A direct current and a water flow rate of 10
      L/min were capable of producing available chlorine (AC) at the rate of 5-8mg/min
      and raising the AC level of the stored tap water by about 0.2 mg/kg within 20-30
      min The electrolyzed tap water with 0.2 mg/kg AC showed a capability per ml of
      killing 10(5)-10(6) cfu of bacteria such as Escherichia coli and Pseudomonas
      aeruginosa within 15 sec. A 6-month trial operation of the storage system with an
      automatic electrolysis control to keep AC level ranging 0.2-0.4 mg/kg
      demonstrated that the system worked well for the stored tap water in suppressing
      bacterial growth as well as in keeping good potable quality with reference to the
      46 parameters specified for Japanese tap water. Actually, the electrolysis
      treatment was administered intermittently with an interval of about two weeks.
      Thus we believe the developed system has good potential to secure a potable water
      supply not only in the occasion of emergencies but also in countries having
      problems in the supply of safe drinking water.

PMID- 17190273
TI  - [Sentinel lymph node biopsy in breast cancer. Experience of the Rome Breast
      Cancer Study Group].
AB  - We report our multicentric experience with sentinel lymph node biopsy for breast
      cancer patients. Patients with breast cancer operated on from January 1999 to
      March 2005 in 6 different institutions in the Rome area were retrospectively
      reviewed. All patients gave written informed consent. 1440 consecutive patients
      were analysed, with a median age of 59 years (range: 33-81) and a median tumour
      diameter of 1.3 cm (range: 0.1-5). Patients underwent lymphatic mapping with Tc99
      nanocolloid (N = 701; 49%), with Evans Blue (N = 70; 5%), or with a combined
      injection (N = 669, 46%). The majority of patients were mapped with an
      intradermal or subdermal injection (N = 1193; 84%), while an intraparenchymal or
      peritumoral injection was used in 41 (3%) and 206 patients (13%), respectively.
      Sentinel lymph nodes were identified in 1374/1440 cases (95.4%), and 2075
      sentinel lymph nodes were analysed (average 1.5/patient). A total of 9305
      additional non-sentinel lymph-nodes were removed (median 6/patient). Correlations
      between sentinel lymph nodes and final lymph node status were found in 1355/1374
      cases (98.6%). There were 19 false-negative cases (5%). Lymph node metastases
      were diagnosed in 325 patients (24%). In this group, micrometastases (< 2 mm in
      diameter) were diagnosed in 103 cases (7.6%). Additionally, isolated tumour cells
      were reported in 61 patients (4,5%). In positive cases, additional metastases in
      non-sentinel lymph-nodes were identified in 117/325 cases after axillary
      dissection (36%). Axillary dissection was avoided in 745/1440 patients (52%). At
      a median follow-up of 36 months, only 1 axillary recurrence has been reported.
      Sentinel lymph node biopsy improves staging in women with breast cancer because
      it is accurate and reproducible, and allows detection of micrometastases and
      isolated tumour cells that would otherwise be missed. Our multicentric study
      confirms that this is the preferred axillary staging procedure in women with
      breast cancer.

PMID- 17190274
TI  - The Italian Registry of Laparoscopic Surgery of the Spleen (IRLSS) A
      retrospective review of 379 patients undergoing laparoscopic splenectomy.
AB  - In December 2000, the Italian Registry of Laparoscopic Surgery of the Spleen
      (IRLSS) was formally launched under the auspices of the Italian Society for
      Endoscopic Surgery and New Technologies (SICE). The aim of this multicentre study
      was to analyse various aspects of the treatment that are still under discussion,
      such as the extension of the laparoscopic indications in cases of malignancy,
      independently of the associated splenomegaly, patient selection and operative
      techniques. A retrospective review of 379 patients undergoing laparoscopic
      splenectomy for haematological diseases from February 1, 1993, to September 15,
      2005, was conducted. Data were collected from the 18 italian centres
      participating in the IRLSS. The mean length of surgery was 140 minutes (range: 25
      420). Conversion was necessary in 25 cases (6.6%), and at least one accessory
      spleen was found in 30 patients (8%). The mean spleen weight was 1200 g (range:
      85-4500). Perioperative death occurred in two cases (0.5%). There were no
      complications in 312 patients (82.3%), with a mean hospital stay of 5.5 days
      (range: 2-30). Morbidity occurred in 67 patients (17.8%), mainly consisting in
      transient fever (n = 22), pleural effusions (n = 16), and actual or suspected
      haemorrhage (n = 14), requiring re-intervention in 7 patients. This first study
      carried out on the IRLSS data shows that laparoscopic splenectomy may constitute
      the gold standard for haematological diseases with a normal-sized spleen. The low
      morbidity and mortality rates suggest that laparoscopic splenectomy can be
      successfully proposed also for splenomegaly in haematological malignancies.

PMID- 17190275
TI  - [Simultaneous laparoscopic treatment for common bile duct stones associated with
      acute cholecystitis. Results of a prospective study].
AB  - Laparoscopy for the management of acute cholecystitis has gained wide acceptance.
      Although it is well known that acute cholecystitis may be complicated by common
      bile duct stones in up to 15% of cases, to date there are no published studies
      addressing the management of common bile duct stones detected during laparoscopy
      for acute cholecystitis. We postulated that, when found, common bile duct stones
      associated with acute cholecystitis could be effectively and safety managed
      during the same laparoscopic procedure. We report on a five-year prospective
      study (2001-2005) involving 313 unselected patients who presented with a clinical
      diagnosis of acute cholecystitis (confirmed by specimen examination) and without
      any contraindication to laparoscopy. At surgery, transcystic cholangiograms were
      obtained in 289 (92%); the other 24 were excluded from the study. With an
      established diagnosis of common bile duct stones, attempts were made to clear the
      common bile duct by transcystic basket retrieval, ERCP or choledochotomy.
      Prevalence of common bile duct stones in acute cholecystitis, success of
      laparoscopic common duct clearance, conversion rate, operative time, morbidity,
      and postoperative hospital stay were the main outcome measures. Common bile duct
      stones were found in 63 pts (21.7%) presenting with acute cholecystitis. At
      laparoscopy, 12 patients (19%) required conversion to open surgery, 3 of these
      being due to failure to achieve common bile duct clearance. Common bile duct
      stones were cleared entirely laparoscopically in 51 patients (81%) by means of
      transcystic stone retrieval (38 pts, 75%), ERCP (12 pts, 23%) or choledocotomy (1
      pt, 2%). At intention to treat analysis, patients undergoing cholecystectomy plus
      common bile duct clearance compared to those undergoing cholecystectomy alone,
      spent significantly more time in the operating theatre (mean 192 min vs 118 min,
      p < 0.001), needed open conversion more frequently (19% vs 6.1%, p = 0.0045), and
      had a higher overall morbidity rate (17.4% vs 4.4%, p = 0.015). The simultaneous
      procedure also adversely affected the postoperative hospital stay (mean 4.8 vs
      3.4 days, p = 0.0164). Mortality was nil in both groups. The prevalence of common
      bile duct stones in patients presenting with acute cholecystitis should not be
      neglected. When common bile duct stones are found, clearance may be obtained
      laparoscopically in a substantial number of cases without any need for open
      surgery. The simultaneous laparoscopic approach for acute cholecystitis and
      common bile duct stones remains, however, a highly skilled and technically
      demanding procedure. Although a moderate incidence of drawbacks is observed, the
      results should be interpreted from the point of view of an all-in-one procedure
      that allows the patients to be cured without needing any further sequential
      interventions.

PMID- 17190276
TI  - The art of decision-making in surgery. To what extent does economics influence
      choice?
AB  - Traditionally most surgeons have paid little attention to the costs of healthcare
      treatments. With the increase in the number of efficacious surgical alternatives,
      a distinct scarcity of available resources has emerged. Since the Eighties, the
      impact of surgical expenditure has been increasing everywhere. The causes are:
      medical progress, increased life expectancy, escalating costs and decreasing
      revenues. The surgeon has been increasingly forced to weigh up theories,
      doctrines and techniques of economics and management. This created new problems
      of choice. In any event, the surgeon's decision-making could lead to negative
      consequences if the primary concern is with the financial constraints and he is
      prompted simply to act rather than to achieve his therapeutic goal. In
      conclusion, although the impact of economic considerations is inevitable in the
      choice of surgery, the terms and methods involved in the process are rather
      ambiguous. In other words, surgeons face with the dilemma of the patient to whom
      the economist denies treatment. To be aware of this issue is the first step, but
      there is still much more to do in order to define the terms of action.

PMID- 17190277
TI  - [Colorectal cancer surgery. Analysis of risk factors in relation to incidence of
      morbidity and mortality].
AB  - The aim of the study was to investigate risk factors in relation to the incidence
      of morbidity and mortality in surgery for colorectal cancer. Between 1986-2005,
      328 patients underwent colorectal cancer surgery, 308 of whom (93.9%) in elective
      and 20 (6.1%) in emergency surgery. Radical resection was performed in 276
      (84.2%) and palliative surgery in 52 (15.8%) patients. Bivariate statistical
      analysis was used for morbidity and mortality factors and multivariate analysis
      was performed in order to find independent variables (age, gender, ASA grade,
      elective or emergency surgery, tumour excision, cancer stage according to Dukes)
      associated with dependent variable interactions. Differences were considered
      statistically significant for p values < 0.05. The incidences of mortality and
      morbidity were 0.91% and 20.1%, respectively. In our study we observed a leakage
      incidence of 2.74% (9/328). In emergency surgery we found morbidity and mortality
      rates of 20% and 10%, respectively. Age and advanced cancer stage influenced
      results but were not found to be statistically significant. 18.3% of patients
      (60/328) were ASA I, 32% (105/328) ASA II, 39.6% (130/328) ASA III and 10.1%
      (33/328) ASA IV. Among the independent variables observed in the multivariate
      analysis, ASA grade was found to be the only positive predictive factor
      correlated with morbidity. Logistic regression showed an exponential increase in
      operative risk: odds ratio (OR) 2.9 in ASA I vs ASA II, OR 4.2 in ASA I vs ASA
      Ill, OR 10.3 in ASA I vs ASA IV (95% confidence interval). As regards the
      mortality rate, none of the independent variables were found to be statistically
      significant risk factors (p < 0.05).

PMID- 17190278
TI  - [Biomolecular prognostic factors in colorectal cancer].
AB  - There is general agreement that staging of colorectal neoplasms based on classic
      anatomopathological parameters does not allow accurate selection of patients at
      higher risk of an adverse outcome. For this reason, identification of new
      prognostic factors is desirable. Such factors should be easily determined and
      expressed at an early stage of carcinogenesis. Moreover, it would be useful to
      identify factors predictive of response to radiotherapy and chemotherapy. Various
      molecules are involved in the carcinogenetic pathway and metastasis formation.
      The aim of this review is to analyse whether any of them are currently useful in
      clinical practice and which of them warrant further study. At present, apart from
      CEA, whose prognostic value has been known for some time, we do not have
      sufficient data to definitively incorporate any of the other biomarkers in
      clinical practice. The most promising factors would appear to be loss of
      heterozigosity of chromosome 18q21 (DCC) and microsatellite instability. However,
      other molecules warrant further in-depth study. In particular, growth factor
      receptors may play a role not only as prognostic factors but also in view of
      their therapeutic potential.

PMID- 17190279
TI  - Cost-revenue analysis in the surgical treatment of the obstructed defecation
      syndrome.
AB  - The obstructed defecation syndrome is a frequent condition in the female
      population. Rectocele and rectal intussusception may cause symptoms of obstructed
      defecation. The aim of this study is to carry out an economic cost-revenue
      analysis comparing the rectocele and the rectal intussusception surgical
      techniques using a double-transanal, circular stapler (Stapled Trans-Anal Rectal
      Resection - STARR) with other techniques used to repair the same defects. The
      analysis involved the systematic calculation of the costs incurred during
      hospitalisation. The revenue estimate was obtained according to the rate
      quantification of the Diagnosis Related Group (DRG) associated with each
      hospitalisation. Our analysis confirmed that the global expenditure for the STARR
      technique amounts to 3,579.09 Euro as against 5,401.15 Euro for rectocele
      abdominal repair and 3,469.32 Euro for perineal repair. The intussusception
      repair cost according to Delorme's procedure amounts to 5,877.41Euro as against
      3,579.09 Euro for the STARR technique. The revenue analysis revealed a
      substantial gain for the Health Authority as regards the treatment of rectocele
      and rectal intussusception for obstructed defecation syndrome. The highest
      revenue, 6,168. 52 Euro, was obtained with intussusception repair with STARR as
      compared to Delorme's procedure which presented revenue amounting to 2,359.04.
      Lower revenues are recorded if the STARR technique is intended for rectocele
      repair; in this case the revenue amounts to 1,778.12 Euro as against 869.67 Euro
      and 1,887.89 Euro for abdominal and perineal repair, respectively.

PMID- 17190280
TI  - Stapled hemorrhoidopexy. Complications and 2-year follow-up.
AB  - Stapled hemorrhoidopexy (SH) presents a number of complications which differ from
      those of traditional haemorrhoidectomy (Milligan-Morgan, diathermy
      haemorrhoidectomy). The follow-up shows better symptom control than other
      surgical techniques. Four hundred and forty-nine patients with haemorrhoids of
      all degrees and mucosal rectal prolapse were treated at our institution over a
      five-year period (1999-2004). Patients were assessed by structural interview to
      assess their symptoms before and after surgery, and surgical and functional
      outcome was assessed at 1, 3, 6, 12 and 24 months. A visual analog scale was used
      for postoperative pain scoring. Patient's satisfaction is the best response to
      all criticism. Bleeding in the early postoperative period occurred in 3.9% of all
      patients and in 7 cases (1.5%) reoperation was necessary. Urge to defecate,
      although present in 14% of patients, disappears in a few weeks. Severe pain, when
      present, may depend on technical failure or learning curve. Complete or
      incomplete recurrence occurred in 10 cases (2.2%). We had one case of
      rectovaginal fistula in a young woman. In 3 cases we underestimated the extent of
      the mucosal prolapse and the patients were reoperated on by stapled transanal
      rectal resection after one (2 patients) and two years. Stapled hemorrhoidopexy is
      a significantly less painful operation and offers significant advantages in terms
      of hospital stay and symptom control in the long term, making for a significantly
      earlier return to work. The complications are similar to those of other
      techniques and are easily resolved. The unusual complications described (rectal
      perforation, pelvic sepsis, rectovaginal fistulas) might suggest that the
      operation should be performed by experienced colorectal surgeons who are familiar
      with the technique and aware of the possible complications.

PMID- 17190281
TI  - [Efficacy of anal dilators in the treatment of acute anal fissure. A controlled
      clinical trial].
AB  - Procedures involving the use of anal dilators or topical nitroderivatives for the
      treatment of anal fissure are efficacious, economic and safe. The aim of our
      study was to compare the efficacy of two conservative treatments - passive
      dilation with anal dilators or topical nitroderivatives - in reducing anal
      pressure and resolving anal fissures. A total of 40 patients with a clinical
      diagnosis of acute anal fissure in the absence of hypotonic anal sphincter,
      abscess or perianal fistula, haemorrhoidal thrombosis, chronic inflammatory bowel
      disease or lower gastrointestinal neoplasia were randomly assigned to treatment
      with dilators (20 patients) or topical nitroderivatives (20 patients). After 4
      weeks of treatment, 90% of patients treated with dilators and only 45% treated
      with topical nitroderivatives showed complete resolution of their anal fissures
      and a reduction of sphincter hypertone. After 12 weeks, 2/18 patients
      successfully treated with dilators and 1/9 patients successfully treated with
      topical derivatives presented recurrence of the anal fissure. The use of anal
      dilators would appear to induce better resolution of acute anal fissures than
      topical nitroderivates, as confirmed by the low relapse rate at 12 weeks.

PMID- 17190282
TI  - [Hemostatic problems in surgery].
AB  - In this study the authors analyse hemostatic problems in surgery, with particular
      reference to the perioperative management of the patient. They examine the
      numerous factors giving rise to hemorrhagic and thrombotic complications, namely,
      the hemostatic technique adopted, the use of drainages, patient risk factors,
      pharmacological prophylaxis, etc. Prevention of bleeding, however, depends
      essentially on adequate preparation of the patient at surgery and on the
      surgeon's skill and experience.

PMID- 17190283
TI  - [Gunshot wounds. Our experience].
AB  - Abdominal gunshot wounds may result in elevated morbidity and mortality. The
      optimal management is still controversial. The authors report on their experience
      with treatment of 49 patients. In all patients the PATI score was used to
      identify trauma and all were treated surgically. Laparoscopy was employed only in
      one patient. The mortality was 2% and the morbidity 6%. The authors conclude that
      the PATI score correlated well with morbidity and mortality. Resuscitation with
      immediate surgical treatment may reduce the morbidity and mortality rates.

PMID- 17190285
TI  - How to improve bilio-stasis in liver surgery.
AB  - One of the most fearful complications following hepatic resection is the onset of
      a biliary fistula. We have attempted to improve intraoperative bilio-stasis to
      minimize the risk of postoperative fistula development by testing different
      materials. In the early 2005 we began employing a collagen sponge coated with
      fibrinogen and thrombin (Tachosil) In our clinical experience, prior to sponge
      use, a biliary fistula developed in 3.9% of elective resections and 5.1% of
      surgical procedures for liver trauma. Until now there were no postoperative bile
      leaks in the patients treated with Tachosil.

PMID- 17190284
TI  - [Merkel cell carcinoma: a report of two cases].
AB  - The Authors report two cases of Merkel cell carcinoma and describe their
      diagnostic and therapeutic difficulties in the management of these tumours. The
      main therapeutic problem consists in establishing the size of the excision
      margins in relation to the neoplastic aggressiveness. The first case was
      characterised by major lymphophilia and by a tendency to relapse. Radical
      excision was achieved by low invasive surgery using a radioguided technique to
      search for microscopic disease. The radioguided technique takes the place of the
      intra-operative anatomo-pathological examination. After adjuvant ra- diotherapy
      and chemotherapy the patienthas remained in remission for three years. The second
      case is characterized by a rapid haematic diffusion with metastasis and exitus
      after one year. Radiotherapy and chemotherapy were ineffective. In this case
      surgery was limited to a bioptic approach since extirpative surgery would have
      been inappropriate. Our experience shows the wide biological variability of
      Merkel cell carcinoma and the importance of eclectic treatment to avoid
      ineffective extirpative surgery.

PMID- 17190286
TI  - Acute para-esophageal hernia in Ehlers-Danlos Syndrome.
AB  - Para-esophageal herniation is a recognized complication of the Ehlers-Danlos
      syndrome. While chronic herniation is well described, acute symptomatic
      herniation is far less common. We describe a case of acute, life-threatening para
      esophageal herniation of the abdominal viscera in a young woman with Ehlers
      Danlos syndrome. Careful anaesthetic assessment and surgical management resulted
      in a successful clinical outcome.

PMID- 17190287
TI  - [Intestinal hemorrhage from diverticulosis of the jejunum: a case report].
AB  - The diagnosis of intestinal diverticulosis is difficult to achieve preoperatively
      because the clinical symptoms are usually non-specific. Intestinal bleeding is a
      rare complication of jejunal diverticulosis. Its diagnosis and treatment can be
      difficult and an emergency laparotomy is often needed. We report a case of
      massive intestinal bleeding from jejunal diverticulosis. The correct diagnosis
      was first suggested by CT and then confirmed at laparotomy. The treatment was a
      segmental jejunal resection with primary anastomosis.

PMID- 17190288
TI  - [Application of biliary stents in endoscopic stenting of biliary ducts].
AB  - Extra hepatic bile ducts with the gallbladder are the center place for many
      disease processes. In extreme cases of significant strictures of bile ducts and
      impairment of bile flow, obstructive jaundice occurs. There are benign and
      malignant biliary strictures. The treatment of obstructive jaundice depends on
      the removal of blockage using endoscopic and surgical methods which return the
      efficient bile flow to the digestive tract. The endoscopic treatment from Vater's
      papilla access using plastic and metal stents is the method of choice. The choice
      of proper prosthesis depends on the reason for biliary strictures. The plastic
      stents (straight, pigtail) are applied the most. Due to their low cost, easy
      insertion to biliary ducts and exchangeability, they are applied in benign and
      malignant strictures. However, metal stents (Wallstent, Diamond, Z-stent,
      InStent), due to the wide diameter after expansion and no possibility of removal,
      are applied only in malignant strictures. Endoscopic insertion of biliary
      endoprostheses can be burdened with complications. There have been reports of
      occlusion, migration with duodenal wall injury and hemorrhaging.

PMID- 17190290
TI  - [Activation of nuclear factor kappaB (NF-kappaB), induction of proinflammatory
      cytokines in vitro and evaluation of biocompatibility of the carbonate ceramic in
      vivo].
AB  - Ceramic materials based on calcium carbonate have been prepared in response for
      the demand for resorbable materials for use in bone surgery. Calcium carbonate in
      the form of crystalline aragonite or calcite with various amount of lithium
      fluoride was the raw material. Material CC-1FA from crystalline aragonite (99%
      CaCO3 and 1% LiF), CC-5FA - from crystalline aragonite (95% CaCO3 and 5% LiF) and
      CC-1FK -material from crystalline calcite (99% CaCO3 and 1% LiF) was studied. To
      evaluate their biocompatibility and inflammatory effect we investigated the
      activity of nuclear factor kappaB (NF-kappaB) and proinflammatory cytokine
      concentrations: tumor necrosis factor TNF-alpha, interleukins 11-6 and IL-8 in
      peripheral human leukocytes (PBL) after stimulation in vitro with tested calcite
      materials. Evaluation of local soft tissue reaction after implantation was also
      the aim of our study. Proinflammatory cytokines take part in inflammatory
      reaction caused by biomaterials. Expression of these proteins is controlled by
      proinflammatory regulatory transcription factors including the commonly appearing
      NF-kappaB (Nuclear Factor kappaB). In a quiescent cell NF-kappaB resides in the
      cytosol in an inactive form which its activated under the influence of kinases.
      The activated NF-kappaB protein translocates from cytosol to nucleus of cell and
      binding to specific DNA sequence it initiates transcriptions. Thanks to the quick
      regulation of immunological response it ensures the survival of cells in
      unfavorable reactions of environmental factors. It regulates the expression of
      many genes mainly connected with the course of the inflammatory process (of some
      cytokines, proteins of acute phase, collagenasis, stromilozine other enzymes
      decomposing the elements of matrix) and with proliferation and differentiating of
      cells. However its excessive activity can lead to unfavorable reactions, for
      example uncontrollable division of cells, appearance of giant cells of foreign
      body type. In our study protein expression of NF-kappaB in PBL were assessed
      using anti-c-Rel-antibody (PBL expressing c-Rel in the nucleus = labelled NF
      kappaB (+) cells). The NF-kappaB activation in PBL was expressed as: the
      percentage of NF-kappaB (+) cells. The level of cytokines: IL-6, IL-8 and TNF
      alpha level in the supernatants from leukocytes culture with tested materials was
      determined by an enzyme-linked immunoabsorbent assay (ELISA) after 24 and 72
      hours incubation. The local tissue reaction in vivo was evaluated 1 and 3 months
      after implantation calcite devices into dorsal muscles of rats. The achieved
      results showed that the tested calcite material incubated 24 and 72 hours with
      PBL culture didn't synthesized higher amounts of the cytokines IL-6 and IL-8 in
      comparison with the untreated cells. All tested materials stimulated after 24 and
      72 hours PBL culture to produce a significant level of TNF-alpha (p < 0.05)
      (higher level after CC-5FA and CC-1FA materials and lower after CC-1FK).
      Activation of transcription factor nuclear factor NF-kappaB in leukocytes after
      24 hours incubation with CC-5FA, CC-1FA was higher than CC-1FK but significantly
      was only after CC-5FA stimulating. The expression of NF-kappaB after 72 hours of
      incubation decreased and was on the level comparable with control group.
      Histological observation 1 month after implantation showed that the carbonate
      ceramic devices were surrounded with connective tissue surrounding implants
      capsule with presence of macrophages. Additionally after 3 month in the dense
      connective tissue cartilaginous and calcification focus was visible. Soft tissue
      reaction showed chronic inflammatory reaction connected with resorbtion of
      biomaterials, the most increased after implantation of CC-5FA, than CC-1FA and CC
      1FK. CONCLUSION: Transcription nuclear factor NF-kappaB was activated after in
      vitro stimulation in short time by the tested calcite material CC-5FA. This
      activity was correlated with induction in vitro of TNF-alpha in short and long
      time. The most increased soft tissue reaction 1 and 3 month after implantation of
      CC-5FA material was found. Our study showed that calcite materials can activate
      NF-kappaB and demonstrated differences in biocompatibility of tested materials.

PMID- 17190289
TI  - [The treatment of abdominal aortic aneurysms by use of endovascular prosthesis
      and classic vascular prosthesis].
AB  - The abdominal aortic aneurysm is a dilatation of infrarenal part of aorta. Its
      ethiology is still unknown. An infection and congenital disorders of conjunctive
      tissue are regarded as the main risc factors. Other factors could be a perimural
      thrombus and elastin and colagen degradation. It's not proved that atheromatosis
      is a risc factor. The disease concerns mainly the old males. Not treated aneurysm
      grows until rupture. The aneurysms are usually asympthomatic. Majority of them
      are found incidentally. Ultrasonography and computed tomography are used to
      extended diagnosis. The open surgery or endovascular surgery are only possible
      ways of treatment. The aneurysm with diameter over 55 milimeters, sympthomatic or
      rupted is an indication for surgery. The aim of the open surgery is implantation
      of the vascular prosthesis into retroperitoneal space. Endovascular method
      consist in placement of stent-graft in the lumen of aneurysm through small
      incision in a peripherial vessel. Stent-graft consists of metal chassis covered
      by classic vascular prosthesis. This method still requires the long-term
      assessment.

PMID- 17190291
TI  - In vitro studies of the properties of thermosensitive systems prepared on
      Pluronic F-127 as vehicles for methotrexate for delivery to solid tumours.
AB  - The aim of the trial was to prepare a thermosensitive vehicles for methotrexate
      which, after implantation to a solid tumour, could form in situ a specific
      implant releasing the active substance at the site of application. Pluronic F-127
      with certain additives, i.e. lactose, glucose, propylene glycol, glycerol and
      sodium phosphate was used for investigations. The sol-gel transition temperature
      of the obtained systems at increasing temperature and various shear rates as well
      as their physicochemical properties were investigated. All the prepared systems
      underwent sol-gel transition at physiological ranges of temperature. Methotrexate
      release from selected formulations approached zero order kinetics and the
      investigations have shown that the use of Pluronic F-127 at concentration of
      14.8% in the construction of drug carriers enables to obtain such a form that,
      depending on the presence of additives and their concentration, provides active
      substance release at any time. Analysis of physicochemical properties of the
      investigated formula tions, i.e. pH, osmotic pressure, density allows to believe
      that their administration by means of a thin needle should not be problematic and
      they will not irritate tissues or cause pain after application.

PMID- 17190292
TI  - Properties and active substance release kinetics from gelatin-alginate matrices.
AB  - The aim of the study was to evaluate the effect of composition and technological
      processing on pharmaceutical availability of active substance as well as on the
      properties of porous gelatin-alginate matrices. The active substance carrier
      included glycerol or peanut oil apart from gelatin and sodium alginate, and some
      matrices were additionally modified with calcium lactate. The obtained matrices
      were characterized by good sorption properties and high resistance to proteolytic
      enzymes. The release of the model antibiotic followed the pattern of first order
      kinetics, while half-release time in vitro (in the experimental conditions) was
      1.5 to 3 hrs.

PMID- 17190293
TI  - Oral implants--quo vadis?

PMID- 17190294
TI  - Trabecular bone response to titanium implants with a thin carbonate-containing
      apatite coating applied using the molecular precursor method.
AB  - PURPOSE: The influence of thin carbonate-containing apatite (CA) coating on the
      trabecular bone response to titanium implants was investigated. MATERIALS AND
      METHODS: Thin CA coatings were deposited by a new method known as the molecular
      precursor method. Using a precursor solution composed of an EDTA-calcium complex,
      a CA film was deposited on the titanium surfaces. Uncoated and CA-coated titanium
      were placed in the trabecular bone of the left and right femoral condyles of 16
      rabbits. After implantation periods of 2, 4, 8, and 12 weeks, the bone-implant
      interface was evaluated histologically and histomorphometrically. RESULTS:
      Histologic evaluation revealed new bone formation around the uncoated and CA
      coated implant surfaces after only 4 weeks of implantation. After 12 weeks,
      mature trabecular bone surrounded all implants. At 4 and 8 weeks of implantation,
      no difference existed in bone contact between uncoated and CA-coated implants.
      After 12 weeks of implantation, the CA-coated implant group showed a
      significantly higher percentage of bone contact than the uncoated implant group.
      DISCUSSION AND CONCLUSION: The present study demonstrated that thin CA coatings
      applied using the molecular precursor method showed greater bone-to-implant
      contact during the healing phase than uncoated controls. The results were similar
      to those observed with implants with calcium phosphate coatings deposited with a
      physical vapor deposition technique.

PMID- 17190295
TI  - Osseointegration of anodized titanium implants coated with fibroblast growth
      factor-fibronectin (FGF-FN) fusion protein.
AB  - PURPOSE: The synergistic effect of fibroblast growth factor (FGF) and human
      fibronectin fragment (hFNIII9-10) on osteoblast cell adhesion has been
      demonstrated in vitro. The purpose of this study was to evaluate the bone
      response around anodized titanium implants treated with FGF-FN fusion protein
      using the histomorphometric analysis and the removal torque test. MATERIALS AND
      METHODS: Threaded implants were manufactured by machining a commercially pure
      titanium (grade 4). Two different groups of samples were prepared: Group 1
      samples were anodized under a constant voltage of 300 V, and group 2 samples were
      anodized under a constant voltage of 300 V and then soaked in a solution
      containing fusion protein (65 microg/mL) for 24 hours. Ten implants from each
      group were placed in rabbit tibiae (1 implant per group per rabbit; each rabbit
      served as its own control). After a 3-month healing period, the animals were
      sacrificed. Removal torque testing and histomorphometric analysis was then
      carried out. RESULTS: The mean removal torque value of group 2 (44.8 Ncm) was
      greater than that of group 1 (37.6 Ncm). The percentages of bone-implant contact
      of the best 3 consecutive threads were 76.37% for group 1 and 88.02% for group 2.
      The percentage of bone-implant contact for the total length of the implant was
      higher for group 2 (36.91%) than for group 1 (29.47%). However, the percentage of
      the area inside the threads that consisted of bone did not differ significantly
      for the 2 groups. DISCUSSION AND CONCLUSION: This study demonstrated that the FGF
      FN fusion protein coating on anodized implants may enhance osseointegration.
      However, the influence of fibronectin- and FGF-treated rough surfaces on long
      term prognosis and the propagation of inflammation are subjects for further
      study.

PMID- 17190296
TI  - Facial development, continuous tooth eruption, and mesial drift as compromising
      factors for implant placement.
AB  - The replacement of teeth lost by children because of trauma can be an important
      indication for early implant therapy. Osseointegrated dental implants, like
      ankylosed teeth, alter position as growth-related changes occur within the
      jawbones (displacement, remodeling, mesial drift). Facial growth of the child and
      even of the adolescent, as well as the continuous eruption of the adjacent
      anterior teeth, create significant risk of a less favorable esthetic and/or
      functional outcome. For patients with a normal facial profile, the placement of
      an implant should be postponed until growth is complete. For patients with a
      short or long face type, further growth, especially the continuous eruption of
      adjacent teeth, creates a serious risk even after the age of 20 years, as
      illustrated by some recent clinical studies. This review aims to explain these
      phenomena and provides some recommendations for implant placement.

PMID- 17190297
TI  - Threaded versus porous-surfaced implants as anchorage units for orthodontic
      treatment: three-dimensional finite element analysis of peri-implant bone tissue
      stresses.
AB  - PURPOSE: A 3-dimensional finite element model was developed to investigate the
      cause of different crestal bone loss patterns observed around sintered porous
      surfaced and machined (turned) threaded dental implants used for orthodontic
      anchorage in a previously reported animal study. MATERIALS AND METHODS: Twenty
      noded structural solid elements with parabolic interpolation between nodes were
      used for modeling the bone-implant interface zone. A 3-N traction force acting
      between either 2 porous-surfaced or 2 machined threaded implants placed in canine
      premolar mandibular sites and bone profiles observed at initiation and 22 weeks
      of orthodontic loading were modeled. RESULTS: Higher maximum stresses in peri
      implant bone next to the coronal region of the implants were predicted with the
      machined threaded implants at both the initial and final time points, with the
      values 20% greater than those predicted after the 22-week loading period. These
      values were approximately 200% greater than those predicted for the porous
      surfaced implants, for which a more uniform stress distribution was predicted.
      DISCUSSION: The finite element model results indicated that the observed greater
      retention of crestal bone next to the porous-surfaced implants was attributable
      to lower peak stresses developing in crestal peri-implant bone with this design,
      which decreased the probability of bone loss related to local overstressing and
      bone microfracture. CONCLUSION: The predicted lower stresses were a result of the
      more uniform transfer of force from implant to bone with the porous-surfaced
      implants, which was a consequence of the interlocking of bone and implant
      possible with this design.

PMID- 17190298
TI  - Cell-based bone reconstruction therapies--cell sources.
AB  - Over the last few decades, reconstructive surgery has shifted from a resection
      oriented approach toward strategies focusing on repair and regeneration of
      tissues. As the main aim of maxillofacial reconstruction has been the restoration
      of bone form and function, surgeons used artificial tissue substitutes in the
      early decades of bone reconstruction. These artificial materials significantly
      improved the ability of surgeons to restore the form and, to some extent, the
      function of defective bones. Despite the fact that every artificial material has
      specific disadvantages, the use of biomaterials is a common treatment option in
      clinical practice even today. Due to the more detailed understanding that exists
      concerning transplantation of cells and tissues, autogenous grafts are the second
      mainstay in clinical practice. However, the main disadvantage of using autogenous
      grafts is donor site morbidity and donor shortage. Research is currently in
      progress into the use of cell-based approaches in reconstructive surgery, since
      cells are the driving elements for all repair and regeneration processes. Various
      cell populations have been reported on in the relevant literature. These cells
      can be classified according to differentiation capacity and the tissue from which
      they originated. In this review, unrestricted cells, multipotential progenitor
      cells, determined cells, and genetically modified cells are described
      systematically, and their advantages as well as limitations are discussed. (More
      than 50 references.)

PMID- 17190299
TI  - Cell-based bone reconstruction therapies-principles of clinical approaches.
AB  - Cell-based bone tissue engineering is a rapidly evolving therapy option in bone
      reconstruction strategies. Some cell-driven approaches, especially the
      biophysical stimulation of the host cell population surrounded by the bone
      defect, are common treatment methods in maxillofacial surgery. Others, such as
      autologous cell implantation, have now gained acceptance for clinical trials.
      More advanced or complex therapeutical options (extracorporeal tissue
      engineering, stem cell use, genetic engineering) have been tested in preclinical
      investigations but have not reached the level of clinical use. Two different
      aspects are of special relevance in cell-based bone reconstruction therapies. The
      source of cells used to regenerate bone (discussed in detail in a complementary
      review in this issue of The International Journal of Oral and Maxillofacial
      Implants) as well as the principal approach of a cell-driven bone regeneration
      therapy influence the outcome of such engineering strategies. All of the cell
      driven repair strategies are under intensive investigation in an effort to
      provide surgeons with a limitless supply of tissue for bone repair and
      reconstruction in future procedures. An overview of the basic biological aspects
      as well as the inherent constraints of different cell-based approaches are given
      in this paper.

PMID- 17190300
TI  - Computerized tomography-assisted calculation of sinus augmentation volume.
AB  - PURPOSE: This study was intended to calculate the augmentation volume for a sinus
      lift procedure based on cross-sectional computerized tomography (CT) scans for 2
      different augmentation heights. MATERIALS AND METHODS: Based on area calculations
      of cross-sectional CT scans, the volume of additional bone needed was calculated
      for 44 sinus lift procedures. The amount of bone volume needed to raise the sinus
      floor to heights of both 12 and 17 mm was calculated. RESULTS: To achieve a sinus
      floor height of 12 mm, it was necessary to increase the height by a mean of 7.2+/
      2.1 mm (range, 3.0 to 10.5 mm), depending on the residual ridge height; to
      achieve a height of 17 mm, a mean of 12.4+/-2.0 mm (range, 8.5 to 15.5 mm) was
      required (P < .01). The calculated augmentation volume for an augmentation height
      of 12 mm was 1.7+/-.9 cm3; for an augmentation height of 17 mm, the volume
      required was 3.6+/-1.5 cm3. Increasing the height of the sinus lift by 5 mm, ie,
      from 12 mm to 17 mm augmentation height, increased the augmentation volume by
      100%. A significant correlation was found between augmentation height and the
      calculated sinus lift augmentation volume (r = 0. 78, P < .01). DISCUSSION AND
      CONCLUSION: Detailed preoperative knowledge of sinus lift augmentation volume is
      helpful as a predictive value in deciding on a donor site for harvesting
      autogenous bone and on the ratio of bone to bone substitute to use. Calculation
      of the augmentation size can help determine the surgical approach and thus
      perioperative treatment and the costs of the surgery for both patients and
      clinicians.

PMID- 17190301
TI  - Immediate loading of implants with 3-unit fixed partial dentures: a 12-month
      clinical study.
AB  - PURPOSE: The aim of the present clinical trial was to evaluate the 12-month
      success rate of titanium dental implants placed in the posterior mandible and
      immediately loaded with 3-unit fixed partial dentures. MATERIALS AND METHODS:
      Patients with missing mandibular premolars and molars were enrolled in this
      study. To be included in the study, the implants had to show good primary
      stability. Implant stability was measured with resonance frequency analysis using
      the Osstell device (Integration Diagnostics). Implants were included in the study
      when the stability quotient (ISQ) exceeded 62. Clinical measurements, such as
      width of keratinized tissue, ISQ, and radiographic assessment of peri-implant
      bone crest levels, were performed at baseline and at the 12-month follow-up. The
      comparison between the baseline and the 12-month visits was performed with the
      Student t test for paired data (statistically significant at a level of alpha =
      0.05). RESULTS: Forty implants with a sandblasted, large grit, acid-etched (SLA)
      surface (Straumann) were placed in 20 patients. At 12 months, only 1 implant had
      been lost because of an acute infection. The remaining 39 implants were
      successful, resulting in a 1-year success rate of 97.5%. Neither peri-implant
      bone levels, measured radiographically, nor implant stability changed
      significantly from baseline to the 12-month follow-up (P > .05). DISCUSSION: The
      immediate functional loading of implants placed in this case series study
      resulted in a satisfactory success rate. CONCLUSION: The findings from this
      clinical study showed that the placement of SLA transmucosal implants in the
      mandibular area and their immediate loading with 3-unit fixed partial dentures
      may be a safe and successful procedure.

PMID- 17190302
TI  - Prosthetic complications with dental implants: from an up-to-8-year experience in
      private practice.
AB  - PURPOSE: Evaluation of prosthetic complication was performed on 236 patients
      treated with 528 implants in an 8-year private practice experience. MATERIALS AND
      METHODS: The study sample included 55 overdentures (ODs) and 265 fixed partial
      dentures (FPDs). Among the latter, 231 FPDs were cemented and 34 were screw
      retained. The type and frequency of prosthetic incidents were recorded, including
      adjustments and complications. Statistical analysis was performed using a chi
      square test to identify risk factors associated with complications. RESULTS AND
      DISCUSSION: Over this period, 1 abut ment fractured and 2 became loose, leading
      to a cumulative implant component success rate of 99.2%. Patients with removable
      prostheses had more complications than those with fixed ones, 66.0% versus 11.5%;
      the difference was significant (P < .001). Posterior fixed prostheses had more
      complications than anterior ones, 11.0% versus 0%; however, the difference was
      not significant (P = .16). The complication rates for cemented and screw-retained
      prostheses did not differ significantly (10.4% versus 5.9%; P = .61). Prostheses
      with an extension cantilever had more complications, 29.4% versus 7.9%; the
      difference was significant (P = .01). In the OD group, the ball-retained
      prostheses had a significantly higher rate of complications than the bar-retained
      ones (77.5% versus 42.9%; P = .04). In the FPD group, complications were not
      recurrent; most occurred during the first 2 years, and the rate of complications
      did not increase with time. In the OD group, 1.3 incidents per prosthesis were
      recorded. Incidents were often recurrent, and the rate of complications did not
      decrease with time. CONCLUSIONS: Removable and fixed prostheses were associated
      with complications at different frequencies and of different types. In the
      removable group, adjustments and foreseeable complications were numerous,
      recurrent, and usually easy to manage. Bar-retained prostheses had fewer
      complications than ball-retained ones. In the fixed group, complications were
      limited in number and did not increase with time. Complications were restricted
      to the posterior region.

PMID- 17190303
TI  - Load fatigue performance of a single-tooth implant abutment system: effect of
      diameter.
AB  - PURPOSE: This study investigated the load fatigue performance of narrow-, regular
      , and wide-diameter CeraOne (Nobel Biocare) single-tooth implants and abutments.
      MATERIALS AND METHODS: Five samples of each implant-abutment combination in 3
      different widths were tested at 3 applied screw torque levels (recommended
      torque, recommended torque +20%, and recommended torque -20%). A rotational load
      fatigue machine was used to apply a 21-N load, at an angle of 45 degrees to the
      long axis of the specimens. This loading produced an effective bending moment of
      35 Ncm at the abutment-implant interface. An upper cyclic limit was set at 5 x
      10(6) load cycles for all specimens. RESULTS: Two-way analysis of variance
      revealed a significant difference between narrow-diameter and wide-diameter
      implant test groups but no significant difference between the 3 torque levels for
      each implant diameter. In the narrow-diameter group, 6 of the 15 specimens failed
      (5 abutment screw failures and 1 implant failure). In the regular-diameter group,
      3 of the 15 specimens failed (2 implant failures and 1 abutment screw failure).
      There were no failures in the wide-diameter group. DISCUSSION: The results of
      this study indicate that the abutment screw is not the only potential failure
      location. The possibility of implant fracture clinically has been previously
      reported for prostheses supported by both single- and multiple-implant
      prostheses. CONCLUSION: The wide-diameter CeraOne single-tooth implant system
      demonstrated superior load fatigue performance. For clinical situations with
      significant functional loading, the narrow-diameter implants would be at a
      greater risk of fatigue failure.

PMID- 17190304
TI  - Immediate function with the zygomatic implant: a graftless solution for the
      patient with mild to advanced atrophy of the maxilla.
AB  - PURPOSE: In many edentulous maxillae, posterior alveolar atrophy calls for bone
      grafting. Patient treatment acceptance is increased by eliminating grafting using
      tilted implants, especially the zygomatic implant in combination with immediate
      function. The purpose of this study was to evaluate a protocol for immediate
      function (within 2 hours) of 2 zygomatic and 4 standard implants (Nobel Biocare)
      supporting a fixed prosthesis in the completely edentulous maxilla. MATERIALS AND
      METHODS: This clinical study included 14 patients with 83 immediately loaded
      implants (28 bilateral zygomatic and 55 premaxillary implants) supporting a
      complete maxillary denture converted to a fixed provisional prosthesis
      immediately following the surgical procedure. After 6 months of use, a new fixed
      metal-supported prosthesis was fabricated. RESULTS: Fourteen patients treated
      with immediate loading of zygomatic implants were followed for at least 12
      months. All patients reported minimization of postoperative pain and security
      during speech, animation, and mastication. No failures occurred during the follow
      up period. DISCUSSION: The patients in the study could have been candidates for
      sinus grafting. With the present concept these patients benefited from a less
      invasive procedure (1 surgical procedure and no grafting) and immediate
      rehabilitation (prosthesis attached directly after surgery). CONCLUSION: The high
      survival rate, increase in patients' immediate functional ability, and reduction
      of morbidity following the surgical procedure render this procedure a viable
      treatment option for the completely edentulous maxilla.

PMID- 17190305
TI  - Pain and anxiety following the placement of dental implants.
AB  - PURPOSE: This study investigated pain experience and anxiety following dental
      implant placement using questionnaires and salivary cortisol measurements.
      MATERIALS AND METHODS: Patients about to undergo implant placement were
      instructed to keep recovery diaries to assess pain experience (limitation of
      activities, postoperative symptoms) and to record average pain, worst pain, and
      interference with daily activities on a visual analog scale (VAS). To assess
      anxiety, patients completed the Spielberger self-evaluation questionnaire and
      collected salivary samples to measure cortisol levels. Saliva was collected 1
      week before surgery, the day of surgery, and 3 and 6 days postoperatively. A
      repeated-measure analysis of variance was used to analyze pain and anxiety data.
      RESULTS: Eighteen patients (12 women and 6 men) who received 30 implants were
      recruited for the study. Following implant placement, most patients reported mild
      to moderate interference with daily activities and postoperative symptoms. No
      patient reported high levels of any symptom. Average pain experience decreased
      significantly with time (F = 6.17; P < .001), from a VAS score of 24/100 on day 1
      to 12 on day 3 and 9 on day 6. Worst pain (F = 7.84; P < .001) and limitation of
      daily activities (F= 6.26; P < .001) were also highest on the first postoperative
      day; they also decreased to about half the maximum level by the second or third
      day. State anxiety, as evaluated by the Spielberger self-evaluation scale, was
      highest on the day of surgery. The salivary cortisol level did not validate this,
      as it did not differ with the time of collection (F = 2.22; P = .075).
      CONCLUSIONS: Patient self-assessment indicates that implant placement is a mild
      to moderately painful and anxiety-provoking procedure. Some limitation of daily
      activities and symptoms are expected to occur, particularly during the first 3
      postoperative days.

PMID- 17190306
TI  - Implant-prosthetic treatment in HIV-infected patients receiving highly active
      antiretroviral therapy: report of cases.
AB  - PURPOSE: Since 1997, the use of highly active antiretroviral therapy (HAART) has
      significantly improved systemic health and life expectancy of patients who test
      positive for the human immunodeficiency virus (HIV) in industrialized countries.
      Therefore, although implant-supported prosthetic rehabilitation has been
      restricted to immunocompetent individuals, it may be considered for these
      patients. CASE REPORTS: The treatment course of implant-prosthetic rehabilitation
      in 3 patients is reported. Patient 1 (male, age 64 years) was under 4-drug
      therapy; patient 2 (male, age 38 years) and patient 3 (female, age 49 years) were
      under 3-drug therapy. Two patients had suffered from AIDS-defining diseases prior
      to HAART. Oral manifestations of HIV infection were not diagnosed throughout the
      observation period. Patients had CD4+ cell counts between 250 and 800/mL, and
      viral load was below 50/mL. Perioperative antibiotic treatment was not applied.
      Two patients presented with edentulous mandibles. In the third patient, single
      tooth replacement of both mandibular first molars was performed. A total of 10
      Frialit-2 implants were placed without augmentation procedures. RESULTS: One
      implant failed after 3 months and was successfully replaced. Two patients
      received magnet-retained overdentures in the mandible, and 1 patient was treated
      with single crowns. All implants and restorations are successfully in function.
      Neither radiographic nor clinical signs of inflammation were detected during the
      observation period (range, 7 to 32 months). CONCLUSIONS: The outcomes of the 3
      patients suggest that immunologically stable HIV-positive patients on HAART may
      be considered for implant-prosthetic rehabilitation.

PMID- 17190307
TI  - Hope drives antiaging hype.

PMID- 17190308
TI  - Antioxidants and hormones as antiaging therapies: high hopes, disappointing
      results.
AB  - No single agent has been shown to truly reverse aging or increase longevity in
      humans. This article reviews the evidence of efficacy (or lack thereof) for two
      types of agents touted as antiaging therapies: antioxidants (vitamin E, vitamin
      C, and carotenoids) and hormones (growth hormone, testosterone,
      dehydroepiandrosterone, and vitamin D).

PMID- 17190310
TI  - Cystic fibrosis in adults: an overview for the internist.
AB  - The care of patients with cystic fibrosis (CF) has improved over the past 30
      years, and most patients now survive well into adulthood. As a result, clinicians
      other than pediatricians are more likely than in the past to see CF patients and
      manage their respiratory, gastrointestinal, pancreatic, and reproductive
      complications.

PMID- 17190309
TI  - Role of uric acid in hypertension, renal disease, and metabolic syndrome.
AB  - Hyperuricemia has long been known to be associated with cardiovascular disease,
      and it is particularly common in people with hypertension, metabolic syndrome, or
      kidney disease. Most authorities have viewed elevated uric acid as a secondary
      phenomenon that is either innocuous or perhaps even beneficial, since uric acid
      can be an antioxidant. However, recent experiments have challenged this
      viewpoint. In this paper we argue that uric acid is a true risk factor for
      cardiovascular disease. Furthermore, we suggest that the recent increased intake
      in the American diet of fructose, which is a known cause of hyperuricemia, may be
      contributing to the current epidemic of obesity and diabetes.

PMID- 17190312
TI  - The clinical picture. A woman with aplastic anemia and a rash.

PMID- 17190311
TI  - PET and PET/CT imaging: what clinicians need to know.
AB  - Positron emission tomography (PET), once the sole province of academic medical
      centers, is rapidly being adopted in daily clinical practice in community
      hospitals and outpatient centers. It can be especially useful in oncology,
      cardiology, and neurology. We provide an overview of the fundamentals of PET and
      PET with computed tomography (PET/CT) and discuss their current clinical utility.

PMID- 17190313
TI  - Hypotension in the intensive care unit.

PMID- 17190314
TI  - Treating depression in pregnancy: practical suggestions.
AB  - Failure to treat depression during pregnancy can lead to problems for the mother
      and the baby. However, given the lack of convincing evidence of the safety of
      antidepressant drugs to the fetus during pregnancy and lactation, any
      antidepressive treatment plan must be embarked on with caution. The authors offer
      practical guidelines for managing depression during pregnancy and lactation.

PMID- 17190315
TI  - [The effect of halothane or sevoflurane anesthesia on the extracellular
      concentration of dopamine and its metabolites examined by in vivo microdialysis
      techniques].
AB  - BACKGROUND: Volatile anesthetics induce changes in the extracellular
      concentration of dopamine (DA) metabolites in the rat striatum and their
      metabolism might be modified in different manners by different anesthetics.
      Although, we have studied DA metabolism during anesthesia using in vivo
      microdialysis techniques, time dimensional changes were not assessed concerning
      the difference between anesthetics. In the current investigation, the rats were
      anesthetized with halothane or sevoflurane, which has different blood solubility,
      and investigated the effect of anesthetics and time-related development on DA
      metabolism. METHODS: The rats were implanted with a microdialysis probe in the
      striatum and perfusate was introduced to HPLC every 20 min. Anesthesia was
      induced with halothane or sevoflurane for 20 or 60 min, and methamphetamine 2 mg
      x kg(-1) was administered during or after inhalation. RESULTS: Both anesthetic
      agents increased the concentration of DA metabolites, and dose and time
      dependency was more obvious with sevoflurane than with halothane. The increase of
      metabolites was prolonged after halothane anesthesia (20 min), but the effect of
      methamphetamine administered immediately after anesthesia on DA release was not
      enhanced by halothane anesthesia. Sevoflurane, not halothane anesthesia,
      antagonized methamphetamine-induced decrease of metabolites. CONCLUSIONS: Not
      only the difference of blood solubility between halothane and sevoflurane and
      anesthetic effect of time dependency, but also another pharmacological property
      affects DA metabolism, including the change in the activity of dopamine
      transporter during inhalation of anesthetics.

PMID- 17190316
TI  - [The effects of continuous infusion of landiolol on heart rate changes after
      neostigmine-atropine administration during recovery from general anesthesia].
AB  - BACKGROUND: On reversal of muscle relaxants when neostigmine-atropine mixture is
      used, heart rate changes occurr. We examined whether landiolol attenuate the
      initial increases in heart rate after intravenous injections of a neostigmine
      atropine mixture. METHODS: Twenty-four patients were assigned to one of two
      groups (n=12 each): control group and landiolol group. Anesthesia was induced
      with propofol and was maintained with isoflurane-nitrous oxide-pentazocine. A
      mixture of neostigmine 2 mg and atropine 1 mg was injected intravenously over 30s
      in the control group. In the landiolol group, 0.125 mg x kg)-1) x min(-1) of
      landiolol for 1 minute was administered immediately after neostigmine-atropine
      injection. Blood pressure and heart rate were measured noninvasively. RESULTS:
      Heart rate was significantly increased after neostigmine-atropine administration
      compared with that at pre-administration in both groups. At 2 and 3 minutes after
      neostigmine-atropine administration, heart rate in the landiolol group was
      significantly lower than that in the control group. The maximum increase in heart
      rate after the neostigmine-atropine injections was significantly less in the
      landiolol group than that in the control group. Blood pressure showed no
      significant changes in both groups during the observation period. CONCLUSIONS:
      Landiolol was useful for heart rate control after neostigmine-atropine
      administration during recovery from general anesthesia.

PMID- 17190318
TI  - [Anesthetic management for cesarean section involving placenta previa].
AB  - BACKGROUND: There are few consistent anesthetic guidelines how to manage cesarean
      section in the presence of placenta previa. Main problem may be hemorrhage, as
      occasionary unexpected massive bleeding leads to life-threatening hemorrhage.
      METHODS: We investigated retrospectively, covering the period between April 1,
      2001 and September 30, 2005, 30 women with placenta previa who had undergone
      cesarean section. RESULTS: Comparing general anesthesia with regional anesthesia,
      there was not a significant difference between the two. Comparing totalis (T)
      with partial (P) in the classification of placenta previa, infusion and
      hemorrhage in T group were more pronounced than those in the P group. Regarding
      these operations performed during the weekend or at night, shortage of supportive
      anesthesiologist was pointed out. CONCLUSIONS: These results indicate that
      regional and general anesthesia did not differ in the intraoperative incidence.
      In all cases at least two anesthesiologists and at least two venous lines are
      necessary to manage cesarean section in the presence of placenta previa.

PMID- 17190317
TI  - [Perioperative mangement of surgery for abdominal aortic aneurysm associated with
      coronary artery disease].
AB  - BACKGROUND: Patients undergoing abdominal aortic aneurysm (AAA) surgery are at
      increased risk of perioperative cardiovascular complications due to underlying
      coronary artery disease (CAD). We determined retrospectively the incidence of CAD
      and the influence of coronary revascularization and perioperative cardiovascular
      complications in patients for AAA surgery. METHODS: Routine coronary angiography
      (CAG) was performed in 159 patients prior to elective AAA surgery to estimate the
      presence of CAD. To compare risk factors and perioperative cardiovascular
      complications the patients were divided at the time of CAG into three groups:
      previously diagnosed CAD, newly diagnosed CAD and non-CAD. RESULTS: Preoperative
      CAG found 129 patients (81%) with CAD. Among newly diagnosed patients 82% were
      asymptomatic of CAD. Forty-four patients (28%) underwent coronary
      revascularization (17 percutaneous coronary intervention, 3 preoperative coronary
      artery bypass grafting, and 24 combined coronary artery bypass grafting).
      Perioperative cardiac complications occurred in 35 patients (22%). No significant
      difference was found among the three groups in the incidence of perioperative
      cardiovascular complications. Two patients with severe CAD not treated with
      coronary revascularization died of cardiac events. CONCLUSIONS: Perioperative
      management and coronary revascularization should be carried out with more
      cautions in AAA patients to reduce the incidence of cardiovascular complications
      after AAA surgery.

PMID- 17190319
TI  - [Neuropathy in the upper extremity after anesthesia].
AB  - BACKGROUND: The purpose of this study was to demonstrate the frequency of
      neuropathy in the upper extremity after anesthesia. METHODS: We reviewed the
      postoperative courses of 5454 patients who had received surgical procedures at
      the Jichi Medical School Hospital from 2004 January to 2004 December. RESULTS:
      Neuropathy developed in 33 patients (0.7%). In 28 of 33 patients (0.6%), symptoms
      were minor and resolved within a few days. The remaining 5 patients (0.1%) who
      had complained the symptoms immediately after emergence from anesthesia had
      residual symptoms. CONCLUSIONS: In our hospital, the frequency of neuropathy in
      the upper extremities was 0.7%. The majority of the neuropathies, however, were
      minor. Neuropathies persisting for a long time were infrequent complications
      (0.1%).

PMID- 17190321
TI  - [Anesthesia for a patient with polyarteritis nodosa who has a history of multiple
      drug allergies].
AB  - There has been little information about anesthesia for a patient with a history
      of multiple drug allergies. We gave anesthesia for a 32-year-old woman with
      polyarteritis nodosa and history of multiple drug allergies. She was scheduled to
      undergo bilateral tonsilectomy. We could not perform the preoperative screening
      of the drugs using a dermal test because of a high risk of anaphylactic shock.
      Anesthesia was induced with sevoflurane and nitrous oxide and maintained with
      sevoflurane, nitrous oxide, and fentanyl. The intra- and postoperative course was
      uneventful. It is important to inquire history of allergies adequately for
      preoperative recognition of allergens. General anesthesia with sevoflurane would
      be useful for a patient with history of multiple drug allergies.

PMID- 17190320
TI  - [Anesthetic management of endovascular repair for aortic abdominal aneurysm in a
      patient with severe chronic obstructive pulmonary disease].
AB  - A 66-year-old man with severe chronic obstructive pulmonary disease (COPD) was
      scheduled for elective endovascular repair of an aortic abdominal aneurysm and
      femoral-femoral artery bypass. Because spirometry revealed marked reduction of
      percent forced expiratory volume in 1 second (%FEV1.0), postoperative respiratory
      failure was anticipated. Spinal anesthesia and no use of tracheal intubation were
      planned. When the patient entered the operating room, his oxygen saturation
      (SpO2) was 92%. Four ml of isobaric 0.5% bupivacaine was injected intrathecally
      at the L3-4 inter-space using a 25-gauge spinal needle. After the final analgesic
      level of the spinal anesthesia had been ensured at T6, 1.0% lidocaine 5 ml was
      injected intradermally in the right elbow for insertion of a catheter sheath.
      Additional analgesia was acquired with a total of 0.1 mg of fentanyl IV. The
      endovascular repair was completed uneventfully. In conclusion, spinal anesthesia
      combined with local anesthesia in the elbow is useful for management of
      endovascular repair of an aortic abdominal aneurysm in patients with severe COPD
      for whom postoperative respiratory failure is anticipated.

PMID- 17190322
TI  - [Anesthesic management of a patient with Stickler's syndrome].
AB  - Stickler's syndrome is a connective-tissue disease of autosome dominant
      inheritance. This report concerns a 3-year-old girl with Stickler's syndrome who
      underwent arthroplasty under general anesthesia. After slow induction of
      anesthesia with an inhalation anesthetic, neither a oropharyngeal airway nor a
      laryngeal mask airway fitted her, and mask ventilation and endotracheal
      intubation became difficult. Endotracheal intubation was performed not with a
      muscle relaxant but under deep anesthesia. Care should be taken when planning
      anesthesia for a case of this syndrome because airway management is often
      difficult and emergency surgery for detached retinas might be required.

PMID- 17190323
TI  - [Effectiveness of potassium adsorption filter during intraoperative blood
      transfusion in patients with chronic renal failure].
AB  - Two patients with chronic renal failure on hemodialysis, received rapid
      transfusion of packed red blood cells (PRBCs) because of massive intraoperative
      bleeding. To eliminate the excessive potassium in PRBCs, a potassium adsorption
      filter (Kawasumi KPF-4, Kawasumi Laboratories, INC., Tokyo, Japan) was applied
      during surgery. The potassium adsorption filter successfully reduced the
      potassium concentration from 14.4-22.0 mEq x l(-1) to 1.9-3.7 mEq x l(-1). A
      potassium adsorption filter is a simple and useful alternative for removal of
      excessive potassium in PRBCs.

PMID- 17190324
TI  - [A case of atypical malignant hyperthermia which presented a typical rise in Ca
      induced Ca release after the operation].
AB  - A 61-year-old man showed clinical findings which suggest atypical malignant
      hyperthermia after pancreatoduodenectomy. He showed no abnormal findings in
      preoperative examinations. General anesthesia was induced with thiopental,
      fentanyl, and vecuronium, and epidural anesthesia was also used for the
      perioperative management. The surgery went on uneventfully and the patient
      returned to the ward. The laboratory data after the surgery showed extremely high
      creatine kinase and myoglobin. The patient's body temperature rose up and showed
      rigidity. We suspected atypical malignant hyperthermia and began its treatment.
      Four months later, we performed muscle biopsy and Ca-induced Ca release (CICR)
      test, which presented a typical rising pattern. This is the first case of
      malignant hyperthermia which occurred after the surgery and accompanied by a
      typical rise in CICR.

PMID- 17190325
TI  - [Evaluation of a compact device for capnometry of main-stream type compared with
      one of side-stream type in a postoperative care unit].
AB  - BACKGROUND: Pulse oximetry is insufficient for postoperative respiratory
      monitoring. It is better to use capnometry for postoperative patients because it
      is easy to use and useful to monitor patients' breathing. However, capnometry
      must be improved in its wearability and detection capability. Therefore it is not
      used often for postoperative patients as a respiratory monitor. METHODS: We have
      examined a side-stream type capnometer and an improved main-stream type
      capnometer in a post-anesthesia care unit (PACU) to determine which is better as
      a monitor for detection of breathing. A total of 55 patients participated in this
      study. Patients wore a device including a main-stream capnometer and a side
      stream capnometer. Capnograms were recorded while patients were staying in the
      PACU. RESULTS: The main-stream system could detect breathing in all the patients,
      but the side-stream system failed to detect breathing in five patients. The side
      stream device showed a warning of "apnea" for five patients, even though these
      patients were breathing normally. CONCLUSIONS: We conclude that the main-stream
      system is a better monitor of postoperative respiratory condition.

PMID- 17190326
TI  - [Central venous oxygen saturation monitoring was useful in two cases of
      hepatectomy with massive bleeding].
AB  - To maintain adequate hepatic oxygen supply during intra-operative period is very
      important to prevent post-operative liver failure after hepatectomy. One of the
      most useful monitors is hepatic venous oxygen saturation. In the same way,
      central venous oxygen saturation can evaluate balance between oxygen supply and
      demand, and its cannulation is easier and safer than that for hepatic and mixed
      venous oxygen saturation. Two cases of hepatectomy performed with the monitoring
      of continuous central venous oxygen saturation using PreSep Central Venous
      Oximetry Catheter (Edwards Lifesciences) suffered from massive bleeding. For the
      management of the circulation and organ oxygenation, the monitoring of continuous
      central venous oxygen saturation was very simple and useful in these cases.

PMID- 17190327
TI  - [Nurse anesthetist in France].
AB  - We present the system of nurse anesthetist (Infirmier Anesthesiste Diplome
      d'Etat: IADE) in France to the community of Japanese anesthesiologists. This
      French system with 70 years' history is older than the Japan Society of
      Anesthesiologists itself. There are 7000 nurse anesthetists in France now and the
      number of nurse anesthetists increases by 450-500 each year. Training to become a
      nurse anesthetist requires at least two years' experience as a general nurse and
      the general nurse must pass an examination after two years' special training in
      an anesthetistic nurse school to acquire the national certification. The nurse
      anesthetist's profession is regulated by French law. They work in a team with
      certified anesthesiologists. They can perform many kinds of anesthetic tasks
      including tracheal intubation and insertion of arterial catheter under the
      responsibility and supervision of certified anesthesiologists. The nurse
      anesthetists are not allowed to perform spinal, epidural, conduction and local
      anesthesia, although they can maintain these anesthesia and control these
      methods, e.g., by injecting local anesthetic agents through epidural catheter,
      following a specified prescription. The nurse anesthetists are not allowed to
      insert central venous and pulmonary artery catheters, although they can manage
      them. They are allowed to administer inhalation anesthetic agents, and inject
      venous anesthetic agents, muscle relaxants, their antagonists, and opioids by
      their own initiatives, but the decision for the use of catecholamine and
      emergency drugs is reserved to certified anesthesiologists. The nurse
      anesthetists perform other tasks preparing and checking anesthetic agents and
      equipment such as anesthetic machine, monitor, and defibrillator everyday, and
      sometimes use autologous blood recovery systems. The relationship between the
      certified anesthesiologist and the nurse anesthetist is marked by mutual respect,
      confidence and cooperation at each step of the anesthetic management, from
      induction to recovery of anesthesia. We believe that it is very safe for the
      patients to undergo anesthesia performed by nurse anesthetists under the control
      of certified anesthesiologists. We suggest that the introduction of the system
      equivalent to the French concept and improved training of nurse anesthetists can
      be the solution to overcome our current shortage of certified anesthesiologists
      in Japan.

PMID- 17190328
TI  - School health aides. Supporting those other first responders.

PMID- 17190329
TI  - Requisite humility. The pursuit of excellence in EMS.

PMID- 17190330
TI  - Cold, wet and hurt. Hypothermia complicates trauma when a hunter falls fom a
      tree.

PMID- 17190331
TI  - Leadership tips. A time to fight: how do you handle attacks on your peeps?

PMID- 17190332
TI  - It's about time.

PMID- 17190333
TI  - Elks Lodge building collapse.
AB  - Of the 50 patients we anticipated, we evaluated 14 victims, two firefighters and
      two people in the crowd who developed anxiety-related symptoms in reaction to the
      incident. Forty-eight people escaped the building in various ways, with the most
      amazing being when rubble created a hole in the wall that led to a stairwell
      where people were able to get out. We transported 11 patients to the local
      hospital, four were flown to trauma centers in Kansas City, and four refused to
      be transported. Of those four, one later went to the ED, where he was diagnosed
      as having an AMI and was flown to a cardiac center in Kansas City.

PMID- 17190334
TI  - Internal affairs: communicating during a tragedy.
AB  - In the event of a tragedy, a company should have separate crisis communications
      plans for the media, the families of any deceased, those who are injured and
      their families, and the workforce as a whole. We hope sharing our experience will
      help others plan for the crises that can occur in our industry. We all have
      operational plans for addressing the tragedies of others. What we learned at
      Southwest is that it's equally important to have crisis communications plans to
      address those tragedies that hit much closer to home.

PMID- 17190335
TI  - Beyond the basics: interpreting vital signs.

PMID- 17190336
TI  - Companion animals in disaster response planning--the first dog speaks out.

PMID- 17190338
TI  - Microbial inactivation by microwave radiation in the home environment.
AB  - The study reported here looked at the survival of microorganisms (heterotrophic
      plate counts, total coliforms, E. coli, and bacterial spores) in a consumer-type
      microwave oven. Kitchen sponges, scrubbing pads, and syringes were experimentally
      contaminated with wastewater and subsequently exposed to microwave radiation. At
      100 percent power level, it was found that the heterotrophic plate count (i.e.,
      total bacterial count) of the wastewater was reduced by more that 99 percent
      within 1 to 2 minutes, and the total coliform and E. coli were totally
      inactivated after 30 seconds of microwave radiation. Bacterial phage MS2 was
      totally inactivated within 1 to 2 minutes. Spores of Bacillus cereus were more
      resistant than the other microorganisms tested, and were completely eradicated
      only after 4-minute irradiation. Similar inactivation rates were obtained in
      wastewater-contaminated scrubbing pads. Microorganisms attached to plastic
      syringes were more resistant to microwave irradiation than those associated with
      kitchen sponges or scrubbing pads. It took 10 minutes for total inactivation of
      the heterotrophic plate count and 4 minutes for total inactivation of total
      coliform and E. coli. A 4-log reduction of phage MS2 was obtained after 2
      minutes; 97.4 percent reduction was observed after 12 minutes. The authors also
      observed a higher inactivation of B. cereus spores in syringes placed in a
      ceramic container than of spores in syringes placed in a glass container. This
      finding could have some implications for the design of containers to be used in
      exposure of medical devices to microwave radiation. The article discusses the
      implications of these findings for consumer safety in the home environment.

PMID- 17190337
TI  - Strategies for eliminating and reducing persistent bioaccumulative toxic
      substances: common approaches, emerging trends, and level of success.
AB  - This paper reviews nine of the best-known strategies for eliminatine and reducing
      substances in the category known as "persistent bioaccumulative toxic substances"
      (PBTSs). The nine strategies are as follows: 1) Ontario's Candidate Substances
      List for Bans and Phase-outs (1992), 2) Canada's ARET Program (1994), 3) Canada's
      Toxic Substances Management Policy (1995), 4) the Commission for Environmental
      Cooperation's Sound Management of Chemicals Initiative (1995), 5) the Great Lakes
      Binational Toxics Strategy (1997), 6) the U.S. Environmental Protection Agency's
      (U.S. EPA's) draft National PBT Strategy (1998), 7) U.S. EPA's Waste Minimization
      Program (1998), 8) the U.N. Stockholm Convention on Persistent Organic Pollutants
      (2001), and 9) Washington State's Rule on Persistent Bioaccumulative Toxins
      (2006). The review describes the commonalities among the strategies, including
      their goals and principles, design approaches, and other common elements. It also
      discusses several emerging trends, such as the increasing importance of economic
      considerations, human health information, and nonregulatory management
      approaches. The paper concludes with a discussion of how effective the strategies
      have been at achieving their goals of elimination and reduction of persistent
      bioaccumulative toxic substances.

PMID- 17190339
TI  - Assessing the willingness of the public to pay to conserve urban green space: the
      Hangzhou City, China, case.
AB  - The authors assessed the willingness of residents to pay for urban green-space
      conservation in Hangzhou, China, using the contingent-valuation method. The aim
      of the study was to provide policy makers with information that would be useful
      for making informed decisions in urban-development planning. The findings of the
      study are as follows: 1) The willingness of residents to pay for urban green
      space conservation was positively correlated with their perceptions of the
      benefits of green spaces and negatively correlated with perceptions of the
      annoyances. 2) The willingness to pay a higher premium for green-space
      conservation is directly related to gender, income level, and residential
      ownership status. Age and education level are not significantly correlated with
      willingness to pay. 3) A majority of respondents view the conservation of urban
      green spaces as a very important function of the city, and most of them are
      willing to pay additional taxes for this conservation. 4) The total value per
      year to the public of the conservation program in Hangzhou is about $15.4
      million. These qualitative and quantitative findings can be used in the policy
      making process for urban-development plans.

PMID- 17190340
TI  - Measuring up: examining the need to establish State-based biomonitoring programs.

PMID- 17190341
TI  - "The field"--revisited.

PMID- 17190342
TI  - The environmental health specialists network--EHS-Net.

PMID- 17190343
TI  - Profiles in leadership, part I: JEH goes on a quest.

PMID- 17190344
TI  - Environmental tobacco smoke linked to behavior problems.

PMID- 17190346
TI  - Environmental health as homeland security.

PMID- 17190347
TI  - Founding a European Association for health law: the rationale.

PMID- 17190348
TI  - Dementia and the law.
AB  - The care for patients with dementia raises many legal (and ethical) issues. This
      article explores some of the more important topics, i.e. (early) diagnosis of the
      disease, the availability and provision of care, treatment and non treatment
      decisions, and medical research with dementia patients.

PMID- 17190349
TI  - Medical treatment of dementia patients at the end of life: can the law
      accommodate the personal identity and welfare problems?
AB  - This article considers whether two significant philosophical objections to
      autonomy-based legal approaches to decision-making for incompetent individuals
      could be accommodated by the law. These philosophical objections are known as the
      personal identity and welfare problems. The article first sets out the autonomy
      based approaches and their objections. Next, the present legal position is
      briefly canvassed in a comparative vein. Finally, the article suggests how the
      personal identity and welfare problems might be accommodated were legislators
      minded to do so, by proposing specific statutory amendments to the recent English
      legislation on advance decisions and evaluating their viability, particularly in
      light of the European Convention on Human Rights.

PMID- 17190350
TI  - Medical research on patients with dementia--the role of advance directives in
      European legal instruments.
AB  - Current international legal instruments recognise the use of advance directives
      to carry on the will of the dementing research participant beyond the boundaries
      of her present legal capacity. Advance directives are gaining greater recognition
      in patient care than in medical research, where their legal status is still
      somewhat unclear. In particular, the three major international documents on
      medical research - the Council of Europe Convention on Biomedicine and Human
      Rights (ETS 164), its Additional Protocol on Biomedical Research (ETS 195), and
      Directive 2001/20/EC on Clinical Trials on Medicinal Products--give conflicting
      messages on the legal status of advance directives in medical research. This
      article examines the provisions in these documents and their national
      applications in Finland and the United Kingdom.

PMID- 17190352
TI  - European Court of Justice. CJEC 2006/5, case C-466/04, Manuel Acereda
      Herrera/Servicio Cantabro de Salud.

PMID- 17190351
TI  - DNA as taxable property - the elephant in the room or a red herring?

PMID- 17190353
TI  - European Court of Justice. CJEC 2006/6, case C-13/05, Sonia Chacon Navas/Eurest
      Colectividades.

PMID- 17190354
TI  - European Court of Human Rights. ECHR 2006/11 case of Devrim Turan v. Turkey, 2
      March 2006, no. 879/ 02 (third section).

PMID- 17190355
TI  - European Court of Human Rights. ECHR 2006/12 case of Melnik v. Ukraine, 28 March
      2006, no. 72286/01 (Second Section).

PMID- 17190356
TI  - European Court of Human Rights. ECHR 2006/13 case of Dickson v. The United
      Kingdom, 18 April 2006, no. 44362/04 (Fourth Section).

PMID- 17190357
TI  - European Court of Human Rights. ECHR 2006/14 case of D. v. Ireland, 27 June 2006,
      no. 26499/02 (Fourth Section).

PMID- 17190358
TI  - Council of Europe: the recommendation on research on biological materials of
      human origin: another brick in the wall.

PMID- 17190359
TI  - Nurse educators, politics, and policy makers.

PMID- 17190360
TI  - Response to thinking like a nurse.

PMID- 17190362
TI  - "Making a connection": BSN students' perceptions of their reminiscence
      experiences with older adults.
AB  - The projected increase in the diversity of the older adult population in the
      United States has generated a demand for nurses prepared to care for older adults
      from different cultural backgrounds. Nurse educators are challenged to develop
      innovative experiences to help prepare students who are competent in
      gerontological nursing and sensitive to cultural differences. The purpose of this
      study was to examine baccalaureate nursing students' perceptions of their
      reminiscence experiences with older adults. Forty-one nursing students who
      participated in a reminiscence education program during their clinical practicum
      completed an open-ended questionnaire. Data were analyzed, and three major themes
      emerged: "Making a Connection," "Seeing the World Through Their Eyes," and
      "Benefits of Reminiscence." Results indicate that implementing reminiscence
      education programs in clinical experiences can help students develop
      gerontological nursing skills, increase their cultural sensitivity, and improve
      their care of older adults.

PMID- 17190361
TI  - The practice doctorate: perspectives of early adopters.
AB  - The emergence of the Doctor of Nursing Practice (DNP) degree is being described
      as a disruptive innovation that is altering the landscape of nursing and health
      care and creating a great deal of controversy within and beyond the profession of
      nursing. This article proposes that the DNP is actually the natural evolution of
      a larger disruptive innovation begun in the late 1960s with the advent of nurse
      practitioner programs. As expected with disruptive innovations, many challenges
      face those who are early adopters and who forge ahead during the early phase of
      innovation and later during the upmarketing phase. As faculty and administrators
      of one of the early, second-generation DNP programs, the authors are fully aware
      of ongoing discussion and issues related to the practice doctorate. This article
      shares the experiences of this group of early adopters and their insights into
      controversies surrounding the DNP movement.

PMID- 17190363
TI  - Tracking the development of professional values in undergraduate nursing
      students.
AB  - In the current nursing shortage, nurses are frequently making significant patient
      care decisions concerning value-laden clinical issues. A program evaluation study
      was conducted to track professional values over time from entry into a
      baccalaureate program to graduation. Nursing students completed a survey
      measuring professional values upon entry into and exit from the program.
      Comparative analysis of pretest and posttest group means demonstrated
      statistically significant increases in total scores. The highest pretest value
      items were also the highest on the posttest, with the addition of patient
      advocacy. Patient advocacy jumped 16 places from pretest to posttest to become
      the highest-ranked statement upon exit from the program. All of the values rated
      as least valued at pretest remained least valued at posttest; however, the means
      of all but two (participating in nursing research and providing consumer
      education about products/services) increased significantly. The value statements
      with mean scores that increased significantly centered on aspects of nursing
      practice less visible to the lay public and involving interaction with other
      health care providers.

PMID- 17190364
TI  - Student and community outcomes in service-learning: part 1--student perceptions.
AB  - Service-learning has a long and distinguished history of providing valuable
      experiences to students across all academic levels. Professional disciplines are
      well situated to provide students with opportunities related to service-learning
      while also providing needed health care services to communities. This article and
      Part 2 on pages 516-518 of this issue describe a service-learning initiative
      implemented in a bachelor of science in nursing program. Part 1 details students'
      perceptions of outcomes realized from the program, and Part 2 describes community
      outcomes. The purposes of the program were to enhance students' skills in history
      taking, blood pressure and heart rate assessment skills, and beginning counseling
      skills, as well as provide the university community with blood pressure screening
      and counseling in a convenient and accessible location. Data on students'
      perceptions were collected for each semester of the program and for 1 year after
      students' participation in the program. Students perceived gains in blood
      pressure and heart rate skill performance, beginning counseling skills, their
      understanding of tailored client action plans, and their professional commitment
      to the health of the community.

PMID- 17190365
TI  - Student and community outcomes in service-learning: part 2--community outcomes.
AB  - This article is the second of a two-part series reporting outcomes from a service
      learning program implemented in a bachelor of science in nursing program. Part 1
      (on pages 512-515) described students' perceptions of outcomes realized from the
      program, and Part 2 describes the community outcomes. The purposes of the program
      were to provide students with history-taking, blood pressure, and heart rate
      assessment skills, and beginning counseling skills, as well as to provide the
      university community with blood pressure screening and counseling in a convenient
      and accessible location. Data on community outcomes were collected on a continual
      basis during the hypertension screening and counseling program implementation.
      Clients were anonymously surveyed on health behavior actions taken after their
      screening and on the screening process. More than 700 client screenings were
      performed over 2 years, with positive health behavior changes being reported by
      clients.

PMID- 17190366
TI  - Factors related to successful collaboration in community-campus partnerships.
AB  - Collaboration and community partnership have become buzzwords in academic
      settings, which have received little direction regarding how to make these
      efforts successful and sustainable. This study attempted to discern the factors
      involved in setting up one successful community-campus partnership. Four years
      after opening an all-volunteer free health clinic in Laramie, Wyoming, we
      interviewed community members and university faculty who were involved in the
      initial partnership. Analysis of these interviews identified several dynamic
      tensions that kept the group together Communitand moving toward its goal.

PMID- 17190367
TI  - Exploring men's perceived educational experiences in a baccalaureate program.
AB  - Nursing school is the first place that men are likely to experience nursing in
      the professional sense. This study explored and documented men's perceptions of
      their experiences in baccalaureate nursing education. Face-to-face audiotaped
      interviews were conducted with 13 male nursing students who were in their last
      semester at three baccalaureate nursing programs. Qualitative methods were used
      to analyze their responses. The findings showed a lack of enjoyment of nursing
      school, the importance of career opportunities, frustrating communication
      differences, and the desire for more male nurse educators. Recommendations for
      future research include obtaining female students' perspectives on these
      questions, researching male students from different types of programs, and
      studying male graduate students to discover why so few become educators.

PMID- 17190368
TI  - Integrating online discussion into clinical rotations.

PMID- 17190369
TI  - The boundary defining what drugs are and how they may be regulated.

PMID- 17190370
TI  - Influence of ABCB1 C3435T polymorphism on the pharmacokinetics of lansoprazole
      and gastroesophageal symptoms in Japanese renal transplant recipients classified
      as CYP2C19 extensive metabolizers and treated with tacrolimus.
AB  - OBJECTIVE: Lansoprazole and tacrolimus are substrates of ATP binding cassette
      (ABC) transporters such as P-glycoprotein (ABCBI/multidrug resistance 1) and
      cytochrome P450 (CYP). The purpose of this study was to investigate the
      implication of the ABCB1 C3435Tpolymorphism on the pharmacokinetics of (R)
      lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and
      on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus.
      MATERIALS: 24 recipients who were CYP2C19 EMs were studied. METHODS: Oral
      administration of 30 mg lansoprazole was started 2 days before transplantation.
      On Day 2 before and Day 28 after transplantation, the plasma concentrations of
      (R)-lansoprazole and tacrolimus were measured. RESULTS: Pretransplantation, there
      were no significant differences in the pharmacokinetic parameters of (R)
      lansoprazole between the 3 ABCBI C3435T genotypes. However, after renal
      transplantation, the peak plasma concentration (Cma ) and area under the plasma
      concentration-time curve (AUCO-24) of (R)-lansoprazole in patients with the ABCB1
      C3435T C allele significantly increased, but not in patients with the TT
      genotype. These pharmacokinetic variations in (R)-lansoprazole did not influence
      the AUC of tacrolimus. There were no significant differences in the frequency of
      gastroesophageal symptoms among the three ABCB] C3435Tgenotypes. CONCLUSIONS: (R)
      lansoprazole concentrations significantly increased in CYP2C19 extensive
      metabolizers with the ABCB1 C3435T C allele, but not TT genotype, after renal
      transplantation. However, the clinical relevance of this observation may be minor
      because these pharmacogenetic changes were not associated with the occurrence of
      gastroesophageal complications.

PMID- 17190371
TI  - Galantamine reduces smoking in alcohol-dependent patients: a randomized, placebo
      controlled trial.
AB  - INTRODUCTION: The high morbidity and mortality caused by smoking highlights the
      importance of investigating new strategies for smoking cessation or reduction.
      Galantamine is an acetylcholinesterase inhibitor that increases the effect of
      acetylcholine (ACh). The nicotinic ACh receptor is activated via positive
      allosteric modulation (APL). METHODS: We investigated whether galantamine reduces
      smoking by performing a 24-week randomized, placebo-controlled, multicentric
      clinical trial in recently detoxified alcohol-dependent patients. We included all
      study subjects irrespective of an intention or motivation to abstain from
      nicotine. Specific treatment for cessation or reduction of smoking was not
      provided. Smoking behavior was assessed by means of patients' diaries. The
      nicotine metabolite cotinine was measured to verify the number of smoked
      cigarettes as documented in the patient's diary. RESULTS: 114 randomized smokers
      received galantamine (n = 56) or placebo (n = 58) for 12 weeks. Follow-up
      examinations were terminated after an additional 12 weeks without treatment.
      Smoking behavior did not differ between both groups at baseline. After treatment,
      the intention-to-treat analysis revealed significant differences with a 20% lower
      cumulative number of smoked cigarettes and a 15% lower number of smoking days in
      the galantamine group compared to placebo. The average number of smoked
      cigarettes per smoking day as well as the cotinine values decreased about 10%.
      Cotinine values showed a positive correlation with the number of documented
      cigarettes, validating the patients' diaries. CONCLUSION: Our tentative data
      indicate that galantamine reduces smoking behavior even without any additional
      specific intervention. We suggest introducing the term "substitution therapy"
      into the treatment of smoking. This result could open up a new treatment approach
      for groups of patients which usually have a low motivation for change.

PMID- 17190372
TI  - Trospium chloride in patients with neurogenic detrusor overactivity: is dose
      titration of benefit to the patients?
AB  - OBJECTIVE: To determine whether dose titration based on therapeutic response is
      superior to standard dosing of oral trospium chloride in patients with neurogenic
      detrusor overactivity and, moreover, to investigate the possible underlying
      causes of differences in efficacy at equal doses in some patients. PATIENTS AND
      METHODS: Using a double-blind approach, two groups (standard dose and adjustable
      dose) with a total of 80 patients were treated with trospium chloride coated
      tablets for a period of 3 - 5 weeks. Treatment duration and daily doses varied
      depending on change ofurodynamic parameters defined as therapeutic response. In
      Week 1, both groups started on 45 mg/day (3 x 15 mg). In the adjustable dose
      group, it was permissible to increase the daily dose to 90 or 135 mg/day
      depending on the urodynamic treatment response. In contrast, doses remained
      unchanged in the standard dose group although a need for dose adjustment had been
      recognized under the double-blind conditions. Therapeutic response was defined as
      improvement of at least two of the following three urodynamic parameters: bladder
      compliance 2 20 ml/cmH20, maximum cystometric capacity > 250 ml and maximum
      detrusor pressure < 40 cmH20. Changes in individual urodynamic parameters were
      defined as secondary efficacy variables. Primary and secondary parameters were
      assessed by comparing baseline values with those at the end of treatment.
      Therapeutic response was analyzed by using the Fisher-Yates test, and the Mann
      Whitney U-test was used for secondary parameters. Trospium plasma concentration
      was measured to assess patient's compliance and as a tool to elucidate possible
      factors influencing treatment efficacy. Safety and tolerability were evaluated
      based on withdrawal rates and adverse events. RESULTS: Both dose groups had
      comparable baseline characteristics. Therapeutic response was achieved in 58% of
      patients in the adjustable dose group (ADG) and in 72% of those in the standard
      dose group (SDG, p -0.23). Clinically relevant increases in maximum cystometric
      capacity and bladder compliance were observed, and there was a clear decrease in
      detrusor pressure. After Day 7, the daily dose was increased in 52.8% of all
      patients in the adjustable dose group and (seemingly) in 32.5% of those of the
      standard dose group. Further dose escalation after Day 14 was assessed as
      necessary in 15% of the standard dose group and 22% of the adjustable dose group.
      The main changes in urodynamic parameters occurred during the first 7 days of
      treatment, but in some patients it takes a longer time. No statistically
      significant differences between plasma trospium chloride levels in the two dose
      groups were observed at any time, but increase of plasma concentration with
      higher doses became obvious when patients were differentiated to individual dose
      stages. In both groups, the most common treatment-related adverse event was dry
      mouth (ADG 35%, SDG 37%), which never led to discontinuation of treatment. Rates
      of other adverse events such as dry skin, dysopia, increased heart rate and
      gastrointestinal disorders were much lower. CONCLUSION: Generally, in patients
      with neurogenic detrusor overactivity daily doses of 45 mg trospium chloride can
      be considered as being the standard dose, and dose adjustment, e.g. due to
      increased body weight, might usually not be necessary. However, increased daily
      doses of up to 135 mg appear to be safe when prescribed in individual patients
      less responsive to the drug.

PMID- 17190373
TI  - Improved control of niacin-induced flushing using an optimized once-daily,
      extended-release niacin formulation.
AB  - INTRODUCTION: Niacin is a recognized treatment for dyslipidemia due to its
      favorable effects on all lipid parameters. However, the clinical use of niacin
      has been limited by its adverse effects, particularly cutaneous flushing. A newly
      reformulated 1,000 mg niacin ER tablet has been designed to reduce flushing
      relative to the original commercial niacin ER formulation. The aim of this study
      is to compare the incidence, intensity and duration of flushing between the 1,000
      mg reformulated niacin ER and the 1,000 mg commercially available formulation,
      when administered as a single 2,000 mg dose to healthy male volunteers. METHODS:
      This was a double-blind, double-dummy, placebo-controlled, 3-way crossover, flush
      provocation study conducted at a single center. To increase the probability of
      flushing, subjects were administered niacin ER at the upper limit of the approved
      dosage range (2,000 mg), and were precluded from using aspirin or nonsteroidal
      anti-inflammatory drugs (NSAIDs) during the study. Subjects received reformulated
      niacin ER, commercial niacin ER or placebo in a 3-way crossover fashion. The
      primary flushing variable was the occurrence of a flushing event. Secondary
      flushing variables included the number of flushing episodes, intensity and
      duration of flushing for both overall flushing events and for individual symptoms
      of flushing (redness, warmth, tingling and itching). RESULTS: A total of 156
      subjects were enrolled in the study. Of 133 subjects who received at least 1 dose
      of study medication in at least 2 study periods, 89% of subjects experienced
      flushing during treatment with reformulated niacin ER, and 98% of subjects
      experienced flushing during treatment with commercial niacin ER. This difference
      was statistically significant (p - 0.0027). Reformulated niacin ER resulted in a
      42% reduction in median flush intensity (p < 0.0001) and a 43% reduction in
      median flush duration (p < 0.0001) relative to commercial niacin ER. The duration
      of first flushing event was more than 1 hour shorter with reformulated niacin ER.
      During the study, 29% of subjects (45/156) experienced treatment-emergent adverse
      events, which were mostly mild in intensity and considered to be remotely related
      or unrelated to the study drug. CONCLUSION: The 1,000 mg reformulated niacin ER
      tablet substantially decreases the incidence, intensity and duration of flushing
      relative to the commercially available 1,000 mg niacin ER tablet, and represents
      an improved niacin therapy option.

PMID- 17190374
TI  - Comparative pharmacokinetic and pharmacodynamic characteristics of amlodipine
      besylate and amlodipine nicotinate in healthy subjects.
AB  - BACKGROUND AND AIM: Amlodipine, a dihydropyridine calcium antagonist, is
      prescribed for the management of angina and hypertension, and is sold as
      amlodipine besylate. However, a new salt formulation, amlodipine nicotinate, has
      recently been developed. Here, we evaluated the comparative pharmacokinetic and
      pharmacodynamic characteristics of the nicotinate and besylate forms of
      amlodipine. SUBJECTS AND METHODS: A randomized, 2-way crossover study was
      conducted in 18 healthy male volunteers to compare the pharmacokinetics and
      pharmacodynamics of these two forms, i.e. amlodipine nicotinate (test) and
      amlodipine besylate (reference), after administration of a single dose of 5 mg of
      each drug and a washout period between doses of 4 weeks. Blood samples for the
      pharmacokinetic analysis of amlodipine were obtained over the 144-hour period
      after administration. Systolic and diastolic blood pressures and pulse rates were
      recorded immediately prior to each blood sampling. RESULTS: All participants
      completed both treatment periods, and no serious adverse events occurred during
      the study period. After administering a single dose of each formulation, mean
      AUC0-infinity and Cmax values were 190.91+/-60.49 ng x h/ml and 3.87+/-1.04 ng/ml
      for the test formulation and 203.15+/-52.05 ng x h/ml and 4.01+/-0.60 ng/ml for
      the reference formulation, respectively. The 90% confidence intervals of
      test/reference mean ratios for AUC0- infinity and Cmax fell within the
      predetermined equivalence range of 80 - 125%. Pharmacodynamic profiles including
      systolic and diastolic blood pressures and pulse rates exhibited no significant
      differences between the two formulations. CONCLUSION: The two amlodipine
      formulations showed similar pharmacokinetic and pharmacodynamic characteristics
      and the new amlodipine formulation, amlodipine nicotinate, was found to be
      equivalent for pharmacokinetics to the currently available amlodipine besylate
      with respect to the rate and extent of amlodipine absorption.

PMID- 17190375
TI  - Influence of the retinoid acitretin on erythrocyte microrheology in vitro.
AB  - OBJECTIVE: To determine in vitro changes in the microrheology of red blood cells
      (RBCs) treated with acitretin (Ro 10-1670). VOLUNTEERS AND METHODS: Venous blood
      samples were obtained from 27 healthy donors. Washed erythrocytes (5 x 10(6)
      cells/ml) were incubated for 30 min at 37 degrees C in solutions of low (25
      ng/ml) and high (400 ng/ml) acitretin concentration. The whole red cell
      deformability was measured using osmotic gradient ektacytometry. To assess the
      contribution of factors influencing changes in red cell deformability, the
      biophysical state of the phospholipid bilayer was determined using the cation
      osmotic hemolysis technique (COH) and the internal viscosity using electron
      paramagnetic resonance (EPR) spectroscopy. RESULTS: Osmotic deformability studies
      revealed that cells treated with acitretin at low concentration deformed almost
      normally in isotonic medium, but RBCs incubated with high acitretin concentration
      showed distinct loss of deformation. However, in hypotonic medium, cell
      deformability was reduced to abnormally low values and this change was most
      marked with high acitretin concentration. CHO measurements showed that incubation
      of red cells at low acitretin concentration caused a significant increase in
      hemolysis at ionic strengths from 123.2 - 154.0 mmol/1 NaCl in relation to the
      control (p < 0.001). A high concentration of acitretin caused a significant
      increase in COH with high ionic strengths in the range 107.8 - 154.0 mmol/l NaCl
      (p < 0.001) and at low ionic strengths in the range 15.4 mmol/l NaCl (p < 0.05).
      The measurement of RBC intracellular microviscosity showed no statistically
      significant differences between control (6.22+/-0.22 cP) and acitretin-treated
      (6.29+/-0.25 cP) cells. CONCLUSION: The data show that acitretin, even at low
      concentration, is capable of inducing the reduction of red cell deformability. A
      reduced tendency of acitretin-treated RBCs to deform might result from the
      ability of acitretin to perturb the cell shape and membrane viscoelastic
      properties.

PMID- 17190378
TI  - Effects of sirolimus on proteinuria and renal function in focal segmental
      glomerulonephritis.

PMID- 17190376
TI  - Population pharmacokinetics of ibandronate in Caucasian and Japanese healthy
      males and postmenopausal females.
AB  - INTRODUCTION: Ibandronate is a potent, nitrogen-containing bisphosphonate that is
      licensed as a once-monthly oral preparation and is currently in clinical
      development as a novel intermittent intravenous (i.v.) injection in osteoporosis.
      Ibandronate pharmacokinetic (PK) data were used to develop a PK model that could
      ultimately be incorporated into a PK pharmacodynamic (PD) model to assist the
      ibandronate development program through computer-assisted trial design. This
      manuscript reports the use of non-linear mixed-effects modeling to characterize
      the PK of ibandronate, to examine the possible influence of ethnicity on the
      disposition of ibandronate and to develop an appropriate population PK model for
      ibandronate. METHODS: A retrospective, cross-study population PK analysis was
      performed using PK data from five phase I studies with i.v. ibandronate (0.125 -
      2.0 mg) conducted in Caucasian and Japanese healthy male volunteers,
      postmenopausal Caucasian women without osteopenia and postmenopausal Japanese
      women with osteopenia. The following covariates were investigated to establish
      their influence on the central volume of distribution (V1) and drug clearance
      (CL): age, body weight, gender, disease status (healthy versus osteopenic),
      creatinine clearance (CLCR), and ethnicity (Japanese versus Caucasian). Serum
      concentrations of ibandronate were quantified by GC-MS or ELISA, and data were
      modeled using non-linear mixed-effects modeling implemented by the software
      program NONMEM. RESULTS: The PK of ibandronate was adequately described by a
      linear 3-compartment model. Disease status, body weight, gender and CLCR
      significantly influenced ibandronate CL (10 34%) and the latter 3 also influenced
      V1 (20 29%). Ethnicity was not a determinant for ibandronate PK in the final
      model. Although gender was the most influential covariate, differences in V1 and
      CL between the sexes were modest (29 and 34%, respectively) and the overall
      effects on ibandronate exposure (Cmax and AUC) were not clinically relevant. The
      final model described the observed PK of ibandronate well, and all PK parameters
      were estimated with an acceptable degree of precision (SE < 13%). CONCLUSION: The
      PK of i.v. ibandronate was well described by a linear 3-compartment population PK
      model that included disease status, body weight, gender and CLCR as covariates,
      but without greatly affecting ibandronate exposure (Cmax and AUC). Ethnicity did
      not influence ibandronate PK and was not included in the final model.

PMID- 17190377
TI  - Influence of avosentan (SPP3OI) on the pharmacokinetics of a second generation
      oral contraceptive containing ethinylestradiol and levonorgestrel in healthy
      female volunteers.
AB  - BACKGROUND: Avosentan (SPP301) is a potent and highly selective ETA receptor
      blocker and is clinically investigated in diabetic nephropathy. This study was
      designed to evaluate whether avosentan influences the pharmacokinetics of steroid
      oral contraceptives. METHODS: During a run-in phase, 16 healthy females received
      an oral contraceptive containing ethinylestradiol 0.03 mg and levonorgestrel 0.15
      mg for the first 21 days of a minimum of one menstrual cycle. In a subsequent
      double-blind, randomized two menstrual cycle crossover treatment phase, subjects
      received either avosentan 25 mg or placebo once daily concomitantly with the oral
      contraceptive. Serum ethinylestradiol and plasma levonorgestrel concentrations
      were measured on Days 14 and 15 of the two treatment periods for the evaluation
      of the 24-hour kinetic parameters, and an additional sample was collected on Day
      21 to determine their trough concentrations. Serum progesterone, luteinizing
      hormone (LH) and follicle-stimulating hormone (FSH) levels as well as plasma
      avosentan and Ro 68-5925 levels were determined on Days 13, 14, 15 and 21 of each
      cycle of the treatment phase. RESULTS: Avosentan had a statistically significant
      lowering effect of 9 - 15% on the ethinylestradiol serum concentration levels.
      The 90% confidence intervals of the pharmacokinetic parameters did not include 1
      or exceeded the 0.8 - 1.25 acceptance range for lack of interaction. The plasma
      concentration-time curves and pharmacokinetic parameters of levonor-gestrel were
      not statistically different during concomitant treatment with either avosentan or
      placebo. Compared to placebo, avosentan lowered the serum concentrations of
      progesterone statistically significantly by about 8% and increased slightly the
      LH and FSH serum concentrations. Safety and tolerability patterns were comparable
      during avosentan and placebo administration. CONCLUSION: Because of the effect of
      avosentan on the concentration levels of ethinylestradiol and progesterone, it is
      possible that the contraceptive efficacy of low-dose combination oral
      contraceptives may be adversely affected during avosentan treatment.

PMID- 17190380
TI  - Hardware: when to hold 'em, when to fold 'em.

PMID- 17190379
TI  - The classification of antiseptic products to be administered to wounds--another
      borderline case between medicinal products and medical devices?
AB  - The importance of a correct demarcation between a Medicinal Product (MP) and a
      Medical Device (MD) is undisputedly one of the major topics related to the
      development and launch of a new healthcare product. However, for some products
      the correct demarcation between MPs and MDs can turn out to be somewhat
      complicated. This article aims to provide an overview on the existing legislation
      and its adequate application based on a suitable example at hand. Article 2 (2)
      of the European Directive 2001/83/EC as amended by Directive 2004/27/EC on the
      Community code relating to medicinal products for human use stipulates that the
      respective Medicinal Products Legislation must be applied whenever a product can
      be covered by both the definitions for MPs and for products regulated by other
      legal provisions enacted by the European Community, e.g. Cosmetic Products (CPs)
      or MDs. This basic principle implies that the decision to base the risk-benefit
      assessment of the product in question on the Medical Device Directive (MDD) would
      contradict the aforementioned constitutional principle, pursuant to which the
      stricter of the regulatory procedures theoretically possible is to apply in cases
      of doubt. In contrast to the approval procedure established for MPs, the MDD
      requires a Conformity Assessment Procedure to be performed by the manufacturer
      himself and a "Notified Body". Thus, in the majority of cases the responsibility
      for the risk assessment of MDs lies solely with the manufacturer and is prior to
      launch not subject to further scrutiny by regulators. Only in specific cases,
      i.e. for the Conformity Assessment Procedure of Class III MDs which contain an
      Active Pharmaceutical Ingredient one of the Member States competent authorities
      designated in accordance with Directive 65/ 65/EEC has to be involved before
      taking a decision. It is therefore important that the classification of the
      product is carried out carefully in full compliance with existing legal
      provisions, also taking into account the related guidance documents issued by the
      European Commission. The adequate application of these rules is explained using
      the example of the antiseptic compound polihexanide, which is used both in
      approved medicinal products (wound antiseptics) and wound irrigation solutions
      labelled as medical devices.

PMID- 17190381
TI  - Keeping up with HIPAA compliance.

PMID- 17190382
TI  - Networking tech: the ties that bind.

PMID- 17190383
TI  - I.T. at the heart of new hospital.

PMID- 17190384
TI  - Bar codes keeps assets on track.

PMID- 17190385
TI  - Readers' perspectives. Are practice management software vendors doing a good job
      of making their products interoperable with their own electronic medical records
      software and the EMRs of other companies?

PMID- 17190386
TI  - Give kids a smile day! Children's dental health month. Two ODA members share tips
      from their successful programs...

PMID- 17190388
TI  - Creative saving for college.

PMID- 17190389
TI  - OUCH! Doctor, my teeth sure are sensitive!

PMID- 17190387
TI  - Five questiouns dentists should ask about their money. Question 4: how do the
      communities (family, practice, profession, culture, neighborhood, etc.) in which
      I live affect my financial decisions?
AB  - Communities, and the personal value you place on them, affect all your spending,
      both business and personal. Once you begin questioning and analyzing how they
      affect your financial decisions, you will begin making more complete choices -
      the better-informed, the greater chance of success. Society has attached many
      financial expectations to dentists - both good and bad. By participating in this
      part of the Five Questions process, you will be able to separate the business of
      dentistry from the practice of dentistry and your persona beliefs from the
      beliefs of your communities'.

PMID- 17190390
TI  - Use of physician-specific data and flow sheets to improve compliance with
      preventive and screening health care measures.
AB  - BACKGROUND: The benefits of preventive and screening health-care measures have
      been well documented, but physician compliance with these measures has been
      imperfect. This investigation sought to measure and improve compliance of seven
      internists with a range of health-care measures. METHODS: This study had two
      parts. Part 1: Office medical records of seven internists were scored on 36
      measures. Physicians were given their individual and group scores to determine if
      such data would improve future compliance with these measures. A second record
      review was performed six months later, and the two compliance scores for both
      individual physician and the group were compared. Part 2: A flow sheet utilizing
      these 36 measures was custom designed for each physician to determine if this
      tool would increase compliance rates over those determined in Part 1. RESULTS:
      Part 1: Baseline compliance with health measures by these internists was
      approximately 75%. Providing individual and group scores to physicians had no
      significant effect on compliance with these health-care measures as measured by
      the second record review. Part 2: Custom designed flow sheets provided comparable
      compliance rates and were as effective as record review in assessing compliance,
      with some measures improving and some declining in comparison scores on Part 1.
      The flow sheet itself, however, did not increase overall compliance scores either
      for individual physicians or the group as a whole. CONCLUSIONS: Baseline
      compliance with health-care measures was higher in this investigation than
      reported elsewhere. Neither data feedback nor redesigned flow sheets increased
      overall compliance rates, but flow sheets were superior in documenting some
      frequently updated items, such as medication lists. Flow sheets were inexpensive
      and easy to implement. Additionally, flow sheets allowed for more rapid
      assessment of physician performance than time-consuming chart review. Until
      superior methods are widely available, the use of flow sheets in ambulatory care
      should be encouraged.

PMID- 17190391
TI  - Optimizing the medical management of diabetic patients undergoing surgery.
AB  - Patients with diabetes are prone to metabolic derangements because of their lack
      of effective insulin. Comorbid conditions, such as coronary artery disease,
      nephropathy, and autonomic neuropathy warrant preoperative assessment to ensure
      safety in the perioperative period. Preoperative evaluation must include
      assessment of chronic complications of diabetes. A thorough history and physical
      should guide preoperative testing which should be aimed at detecting correctable
      abnormalities and assessing the extent of end-organ disease. Surgery poses
      special challenges to patients with diabetes because the stress response,
      interruption of food intake, altered consciousness, and circulatory alterations
      all lead to unpredictable glucose and electrolyte levels. The management of
      insulin perioperatively depends on the preparation normally taken by the patient,
      and the glucose level on the morning of surgery. The goal is to avoid
      hypoglycemia and extreme hyperglycemia. Oral hypoglycemic agents should be held
      on the morning of surgery. Metformin should be discontinued 48 hours prior to and
      subsequent to surgery in order to reduce the risk of lactic acidosis. The
      avoidance of hypoglycemia and excessive hyperglycemia intraoperatively is best
      achieved with frequent monitoring of blood glucose and treating abnormalities
      according to patients' preoperative regimen and current condition. Maintaining
      blood glucose levels below 110 mg/dL reduces morbidity and mortality in
      critically ill patients. Measure blood glucose immediately following surgery
      because progression of the stress response postoperatively, in addition to
      possible nausea and vomiting, can complicate the patient's management.
      Precautions should be taken to prevent damage to peripheral nerves while
      diabetics are on the operating table because their nerves and limbs are already
      vulnerable to pressure and stretch injuries secondary to neurologic and vascular
      disease. With thorough and careful management, metabolic control in the
      perioperative period is a goal that is attainable for most patients.

PMID- 17190392
TI  - A New England bonesetter dynasty: the Porters of Farmington, Connecticut--Part II
      of II.
AB  - Daniel Porter (d. 1690), a bonesetter/ chirurgeon, one of the early settlers of
      the Connecticut Colony, was the first and only doctor serving the Farmington
      valley during much of the second half of the 17th century. More than forty of his
      descendants, spanning eight generations and almost three centuries, practiced
      medicine and surgery, moving with the migration of the expanding population to
      towns throughout New England, New York State, and ultimately the midwest and west
      coast. Their notable accomplishments, apart from their consistent reputation for
      exceptional skill and endurance, include the training and independent practice as
      bonesetters of two of their wives. In 1796, Samuel Lee, Jr., (1773-1814), a fifth
      generation descendant, received the first U.S. patent for a medication, "Samuel
      Lee's Genuine Windham Bilious Pills." The last Porter doctor to be identified,
      Charles Allen Porter (1866-1931), a pioneer Professor of Surgery at Harvard
      Medical School, was among the first to recognize the carcinogenic effects of
      radiation. In the absence of a comprehensive published genealogy of the Daniel
      Porter family, this essay identifies the relationships among his many
      descendants.

PMID- 17190393
TI  - Recollection: Christmas Eve in Cherbourg--1944.

PMID- 17190394
TI  - The doctor in colonial Connecticut. 1956.

PMID- 17190395
TI  - "Safer, but not safe enough".

PMID- 17190396
TI  - Address of the new president. CSMS annual meeting--house of delegates September
      28, 2006.

PMID- 17190398
TI  - Address of the executive director. CSMS house of delegates--annual meeting.
      September 28, 2006.

PMID- 17190397
TI  - Wondering about the workforce.

PMID- 17190399
TI  - ABFM's recertification examination.

PMID- 17190400
TI  - Improving function through research.

PMID- 17190401
TI  - The value of reality orientation with older adults who are mentally III: a study
      from the Republic of Ireland.
AB  - The goal of this study is to bring to the fore information that provides greater
      insight into the value of Reality Orientation (RO) in caring for older adults.
      More particularly, the author conducted this study for two reasons. First, he
      observed a tendency for himself and his colleagues to use RO in caring for older
      adults with mental illness, and second, there exists a paucity of recent research
      based literature related to RO. The majority of research articles reviewed were
      quite old, originating in the late 1970s to early 1980s (e.g., Brook, Degun, and
      Mather [1975]; Zepelin, Wolfe, and Kleinplatz [1981]). Finally, this article
      focuses on how nurses perceived RO within an elderly mental health care setting
      within the Republic of Ireland.

PMID- 17190402
TI  - Medical decision-making in the nursing home: a comparison of physician and nurse
      perspectives.
AB  - The purpose of this study is to clarify the perspectives of physicians and nurses
      in the medical decision-making process at the time of status change events in
      nursing home residents. The decision-making processes studied involved 28
      cognitively impaired nursing home residents in a large suburban nursing home. In
      interviews, the authors ascertained the personal opinions of physicians and the
      nurses related to the status change event and the decision-making process using
      the Medical Decision-Making During a Status Change Event Questionnaire. Nurses
      reported a greater degree of familiarity with the family's and resident's wishes
      than did physicians. Physicians reported considering more treatment options and
      choosing more treatments for residents than nurses. Both physicians and nurses
      reported that the physicians had a major role in decision-making and that nurses
      did not, yet the gap in reported roles was greater based on physicians' reports
      in comparison to nurse reports. In a third of the reported cases, physicians and
      nurses disagreed about whether advance directives had been followed. These
      findings reflect a division of roles and perspectives of nurses versus physicians
      in the medical decision-making process. This study demonstrates the ability of
      the questionnaire to reveal several key differences in perceptions of care. This
      information could be useful in developing forums for communication among the
      professionals to enhance mutual understanding.

PMID- 17190403
TI  - Diagnosing and treating benign paroxysmal positional vertigo.
AB  - Gerontological nurses play a critical role in the early recognition of benign
      paroxysmal positional vertigo (BPPV), a condition that accounts for approximately
      50% of vertigo in older adults. BPPV results in vertigo when debris collects in
      one or more of the semicircular canals, most typically the posterior canal. It
      may be differentiated from other forms of vertigo because it results in dizziness
      when recumbent or with head position changes. BPPV may be successfully treated
      with repositioning therapy, such as the Epley maneuver. Nurses working in medical
      offices, longterm care facilities, and assisted living may be called on to
      perform this maneuver. Gerontological nurses play a key role in assessing and
      treating BPPV, therefore minimizing unnecessary testing and medication and
      reducing the suffering and expense for patients with this condition.

PMID- 17190404
TI  - The association of physical function with agitation and passivity in nursing home
      residents with dementia.
AB  - The purpose of this article is to examine the association of physical function
      with agitation and passivity in nursing home residents with dementia using direct
      observational measures. Data were analyzed using mixed model analysis of
      variance. This study was a secondary data analysis using baseline data yielded
      from a crossover experimental study. Univariate analyses showed that physical
      function, cognitive status, and education explained a significant amount of
      variance in agitation. When controlled for cognitive status and education,
      physical function lost significance and only explained 2.6% of the variance in
      agitation. It was found that physical function was not related to passivity.
      Environmental factors may be more salient antecedents for agitation and passivity
      in nursing home residents with moderate to severe cognitive impairment.

PMID- 17190405
TI  - Richmond Instructive Nurse's Visiting Association.
AB  - 1. In the beginning of the 20th century, the provision of nursing services to
      older adults took a lesser role behind the focus on communicable diseases and
      maternal and infant care. 2. The Instructive Visiting Nurse's Association records
      in Richmond, Virginia provide a snapshot into the delivery of home-based care to
      older adults from 1900 to 1929. 3. Financing care of the U.S. elderly population
      has been an ongoing issue for more than 100 years.

PMID- 17190406
TI  - Lessons from my father.

PMID- 17190408
TI  - Consequences of poor evaluation.

PMID- 17190407
TI  - Physicians and industry: regaining independence.

PMID- 17190409
TI  - Arkansas Health Summit overview.

PMID- 17190410
TI  - Arkansas hospitals showing success in transition to HIT. Stuttgart Regional
      Medical Center meets challenges, reaps benefits.

PMID- 17190412
TI  - A chilling case.

PMID- 17190411
TI  - Meet our members. Carl Covey, MD.

PMID- 17190413
TI  - Management of childhood hypertension: a guide for primary care physicians.
AB  - Prevalence of pediatric hypertension has increased with the onset of obesity
      epidemic. Early detection and treatment of childhood hypertension is important
      due to its link with atherosclerosis in adult life. Accurate measurement of blood
      pressure is the key for the management and physicians should make effort to rule
      out the possibility of anxiety associated and white coat hypertension before the
      final diagnosis of hypertension. Secondary hypertension is more common in
      children as compared to adults but essential hypertension is also common in older
      children and adolescents. The younger children with severe hypertension are more
      likely to have secondary hypertension. Non-pharmacologic treatment should be
      tried before instituting the pharmacologic treatment, unless patient is
      symptomatic and has severe hypertension.

PMID- 17190414
TI  - [Clinical research of vestibular autorotation test for patients with
      vertebrobasilar insufficiency].
AB  - OBJECTIVE: To explore the diagnostic values of vestibular autorotation test (VAT)
      for patients with vertebrobasilar insufficiency (VBI). METHODS: VAT and
      videonystagmography ( VNG) were performed on 73 patients with VBI and 48 patients
      with peripheral vestibular lesions (contrast group). Parameters analyzed included
      Gain, phase and asymmetry of VAT, as well as the canal paresis (CP) of caloric
      test and results of optokinetic-pursuit tests in VNG. Positive result of the test
      could be defined if anyone of the parameters was abnormal. RESULTS: For VAT test,
      Gain was enhanced in VBI group and was reduced in contrast group. In VBI group
      and contrast group, Gain enhanced showed in 47 (64.4%) cases and 5 (10.4%) cases,
      respectively (chi2 = 31.19, P < 0.01). Simultaneity, Gain reduced in 11 cases
      (15.5%) and 22 cases (45.8%), respectively (chi2 = 13.82, P < 0.01). But there
      was no statistics significant for results of the parameters of phase, asymmetry
      and integration between two groups. For VNG test, results with optokinetic
      pursuit tests were more abnormal in VBI group than that in contrast group, which
      showed central lesions characteristics. Forty-four cases (60.3%) in VBI group and
      10 cases (20.8%) in control group showed central lesions results with optokinetic
      pursuit tests and visual fixation test (chi2 = 15.89, P < 0.01). Unilateral or
      bilateral CP showed in 33 cases (68.6%) in control group and 51 cases (69.9%) in
      VBI group with caloric test. CONCLUSIONS: Gain of VAT is mostly enhanced in VBI
      group, and Gain as a main characteristic is reduced in patients with peripheral
      vestibular lesions. The Gain parameter is availability for assessing
      characteristics of vestibular lesions. Phase and asymmetry can be used to assess
      the vestibular function but can not indicate the characteristics of vestibular
      lesions.

PMID- 17190415
TI  - [Neurootological manifestation of migrainous vertigo].
AB  - OBJECTIVE: To analyzed the characteristics of migrainous vertigo (MV), a kind of
      paroxysmal vertigo, in order to demonstrate the extent of damage and dysfunction
      in MV and to judge whether MV is peripheral or central vertigo. METHODS: Twenty
      two cases of acute (5 cases) or subacute (17 cases) MV were examined with oto
      neurological tests, spontaneous nystagmus, positional nystagmus and auditory
      tests. RESULTS: There were 6 males and 16 females. Among those patients, 15 had
      migraine, 17 motion sickness, 15 family history of migraine or motion sickness, 1
      visual aura, 7 motion intolerance (vertigo from head movement and body movement),
      4 photophobia, 6 phonophobia and 5 vertigo from insomnia and emotion. There were
      likely to have vertigo in menstrual period in 2 cases. The duration of vertigo
      lasted from minutes to days. For pure-tone audiometric, 9 were normal which from
      mild to moderate hearing loss. Three cases had abnormal high frequency ABR
      bilaterally and 10 abnormal unilaterally. Subjective visual vertical were normal
      in all of the cases. Vestibular evoked myogenic potentials were abnormal in 14
      cases (13 had low amplitude and 1 had longer latency of P13 wave). Bithermal
      caloric test was abnormal in 3 cases and 11 had abnormal ocular movement (9 with
      low gain of optokinetic nystagmus, 1 with overshoot in saccade and 1 with
      vertical nystagmus after head shaking), in which 10 had abnormal high frequency
      ABR and 1 was normal. CONCLUSIONS: MV could be peripheral or central vertigo and
      MV should be included in the differentiation of peripheral and central vertigo.

PMID- 17190417
TI  - [One case of pneumatolytic middle turbinate infection accompanied with
      rhinolith].

PMID- 17190416
TI  - [Functional localization of vestibular cerebral representations in human using
      functional magnetic resonance imaging].
AB  - OBJECTIVE: To study human vestibular cerebral representations by combining right
      sided ice-water stimulation at 0 degree C with blood oxygenation level dependent
      functional magnetic resonance imaging (BOLD-fMRI) and to evaluate the value of
      this method in the functional localization of human vestibular cortex. METHODS:
      Twenty right-handed volunteers (12 men and 8 women) received unilateral
      irrigation of the right external auditory meatu for 15 s with 15 ml of water at 0
      degrees C during fMRI in complete darkness. The functional imaging of brain
      cortex was acquired with a 1.5-T MRI scanner (Signa Infinity Twin + Excite;
      General Electric Co., USA). The successive functional images from each subject
      were analyzed as a group with statistical parametric mapping software (SPM 99).
      RESULTS: Ultimately, data obtained from 17 subjects were analyzed (3 subjects
      were eliminated from data because of head movement exceeding 2 mm). The group
      analysis showed bilateral (particularly left-sided) cortical activation,
      associated with caloric stimulus involving in temporoparietal junction extending
      into the posterior insula, supramarginal gyrus in the inferior parietal lobe,
      precuneus, supplementary motor area (SMA), the ventrolateral portion of the
      occipital lobe, cuneus and lingual gyrus, superior temporal gyrus and cingular
      cortex. CONCLUSIONS: Ice-water stimulation at 0 degree C in fMRI reveals a
      widespread cortical network involved in vestibular signal processing in human. As
      the functional localization of vestibular cortex could be determined precisely,
      ice-water stimulation at 0 degree C in fMRI would hold great promise as a
      sensitive and reproducible tool for the research in human vestibular cortex.

PMID- 17190418
TI  - [Clinical significance of vibration-induced nystagmus in patients with unilateral
      peripheral vestibular disorders].
AB  - OBJECTIVE: To clarify the clinical significance of vibration-induced nystagmus
      (VIN) and to calculate the sensitivity and the specificity of the vibration test.
      METHODS: One hundred and twelve patients with unilateral peripheral vestibular
      disorders and 30 normal subjects were enrolled into this study. However, patients
      with spontaneous nystagmus were excluded. Vibratory stimuli (approximately 92Hz)
      were presented to the mastoids and the forehead. Patients and normal subjects
      also underwent head shaking testing and caloric testing. RESULTS: Of the 112
      patients, 91 (81%) showed VIN which were mainly horizontal. VIN was more
      frequently evoked on the mastoids than on the forehead. In the majority of
      patients (76 cases), the direction of VIN was toward the healthy side, whereas
      patients with Meniere's disease (15 cases), showed nystagmus toward the affected
      side. None of 30 normal subjects showed VIN. Whereas, HSN was found in 70 (63%)
      patients and 9 (30%) in normal subjects. Of 112 patients, 10 showed a canal
      paresis (CP) value of caloric test less than 25% ,while 32 with a CP value
      between 25% and 40%, 48 with a CP value between 40% and 70%, and 22 with a CP
      value more than 70%. It is notable that with increasing canal paresis value on
      caloric testing, VIN was more likely to be evoked. CONCLUSIONS: VIN testing is a
      simple, non-invasive and well-tolerated clinical test that indicates unilateral
      peripheral vestibular dysfunction. VIN testing had greater sensitivity and the
      specificity than HSN testing in the diagnosis of unilateral peripheral vestibular
      disorders.

PMID- 17190419
TI  - [Replantation of amputated ear with microtechnique].
AB  - OBJECTIVE: To report replantation of amputated ear with microtechnique in 5
      cases. METHODS: From 2002 to 2005, 5 totally amputated ears were replanted and 4
      obediently, 1 retrogressively. In every case, 1-2 arteries and 1-3 veins were
      anastomosed. Seven vessels were detective and 1-6 cm vessels were transplanted
      from forearm or dorsal side of hand. Amputated ears obtained blood supply again
      in about 6-10 hours after injury and exploration was enforced for venous crisis
      in 2 cases, and bloodletting in 1 case. RESULTS: All 5 cases survived. Auricles
      possess perfect shape, no pigmentation, slight atrophy and perfect sensation.
      CONCLUSIONS: Amputated ear should be replanted as long as no obvious contusion
      occurred, and the keys to prevent vascular crisis are cutting off unhealthy
      vessels, grafting superficial veins for bridging, and the high quality of
      vascular anastomosis.

PMID- 17190420
TI  - [Spiral computed tomographic analysis of frontal recess regions].
AB  - OBJECTIVE: The purpose of the study was to determine the prevalence of frontal
      recess cells in Chinese patients who did not have frontal sinus disease related
      symptoms. METHODS: Forty-nine Chinese patients without frontal sinus disease
      symptoms were undergone spiral computed tomography (CT). Then multiplanar
      reconstruction images were evaluated using a standard triplanar reconstruction
      protocol on a computer workstation. RESULTS: The prevalence of agge rnasi cell
      was 94% (92/98). Sixty-four uncinate processes (65%, 64/98) had one superior
      attachment for each uncinate process, the other thirty-four uncinate processes
      (35%, 34/98) had two superior attachments for each uncinate process. The uncinate
      process' single superior attachment into the surrounding structures was
      identified to have the following distribution: 53% (52/98) to the lamina
      papyracea, 9% (9/98) to the middle turbinate, 3% (3/98) to the skull base. Most
      of the uncinate process' two superior attachments were either into the lamina
      papyracea and the skull base (24%, 23/98) or into the lamina papyracea and the
      middle turbinate (10%, 10/98). Only one uncinate process (1%) superiorly attached
      to the skull base and the middle turbinate. The prevalence of recessus terminalis
      was 87% (85/98). Of all the frontal cells identified in 32 sides (33%) of frontal
      recesses, the prevalence of type I, type II, type II and type IV cells were 23%
      (23 sides), 2% (2 sides), 7% (7 sides) and 0% (0 side) respectively. Supra bullar
      cell, frontal bullar cell and interfrontal septal cell were identified in 30
      sides (31%), 7 sides (7%) and 7 patients (14%) respectively. CONCLUSIONS: The
      result characterized normal frontal recess pneumatization in Chinese. That,
      together with the variations of the uncinate process' superior attachment
      emphasized the roles of agger nasi cell and the uncinate process in endoscopic
      frontal sinus surgery.

PMID- 17190421
TI  - [Quality of life survey on patients with chronic rhinosinusitis and nasal
      polyps].
AB  - OBJECTIVE: To explore the health-related quality of life (QOL) status of patients
      with chronic rhinosinusitis and nasal polyps. METHODS: One hundred and twenty
      patients with chronic rhinosinusitis and nasal polyps and two hundred individuals
      passing health examination were enrolled by random and their QOL scores were
      assessed by using QOL instruments including existing SF-36 questionnaire (Chinese
      version ) and SNOT-20 questionnaire translated into Chinese, of which clinimetric
      and psychometric properties were tested. RESULTS: The feasibility, reliability,
      validity, and responsibility of Chinese version of SNOT-20 questionnaire all
      passed the test. By the assessment of SF-36 questionnaire, it revealed that
      scores of six domains such as physical functioning, role physical, bodily pain,
      mental health, vitality, and general health from patients with chronic
      rhinosinusitis and nasal polyps were lower than that of control group except
      social functioning and role emotional (P < 0.05). It showed by Chinese version of
      SNOT-20 questionnaire that patients exceeded healthy individuals in the scores of
      twenty items of three domains including physical problems, functional
      limitations, and emotional consequences, of which the most five important items
      affecting health status were respectively need to blow nose, thick nasal
      discharge, lack of a good night's sleep, dizziness, and post-nasal discharge (P <
      0.05). CONCLUSIONS: QOL instruments such as Chinese version of SF-36 and SNOT-20
      questionnaires can effectively differentiate the QOL status between patients with
      chronic rhinosinusitis and nasal polyps and healthy individuals. The negative
      impact of chronic rhinosinusitis and nasal polyps on patients' QOL includes
      physical functioning, role physical, bodily pain, mental health, vitality,
      general health, and emotional consequences. The problems of nasal discharge,
      sleep, and dizziness should be sufficiently emphasized in clinical treatment.

PMID- 17190422
TI  - [Preoperative overnight airway pressure measurement for predicting the outcome of
      revised uvulopalatopharyngoplasty].
AB  - OBJECTIVE: The distribution of upper airway obstruction sites can be identified
      quantitatively and dynamically with continuous airway pressure measurements in
      obstructive sleep apnea hypopnea syndrome ( OSAHS) patients. Its value as a
      clinical predictor for the outcome of revised uvulopalatopharyngoplasty was
      evaluated. METHODS: The upper airway obstruction sites (transpalatal level,
      tongue base or hypolarynx level) were determined preoperatively with overnight
      upper airway pressure monitoring and concurrent polysomnography (PSG). Of one's
      total amount of obstructive events, the proportion of apnea/hypopnea events
      located at Transpalatal level was quantified as contribution of transpalatal
      obstruction. Of all OSAHS patients, 26 males and 1 female underwent revised
      uvulopalatopharyngoplasty (2 had same stage transpalatal advancement
      pharyngoplasty) and had follow-up PSG 6. 33 +/- 0.84 months after surgery. The
      relationship of transpalatal obstruction proportion, age, tonsil size and body
      mass index (BMI) and the reduction in apnoea hypopnea index (AHI) was analyzed.
      RESULTS: The AHI (times/hr) of 27 subjects decreased from 63.9 +/- 20.7 to 28.4
      +/- 25.4. The response rate was 51.9% (defined as AHI reduction over 50%).
      Correlation between the transpalatal obstruction proportion and the AHI reduction
      percentage was significant (r = 0.609), so was the degree of the tonsil size (r =
      0.511). The proportion of tongue base level obstruction showed a negative
      correlation for the AHI reduction. Patients with oropharynx obstruction
      percentage > or = 70% had a success rate of 90% and all patients with oropharynx
      obstruction percentage <60% responded poorly to the operation. The regression
      model showed distribution of obstructive sites, along with tonsil size and other
      PSG parameters could predict 66.7% of the postoperative AHI of transpalatal level
      surgery (F = 6.701, P = 0.001) . CONCLUSIONS: Contribution of transpalatal level
      obstruction has significant predictive value to the outcome of transpalatal level
      surgery in OSAHS patients.

PMID- 17190423
TI  - [Two cases with rabies first presented symptom of pharyngalgia].

PMID- 17190425
TI  - [Supraglottic horizontal partial laryngectomies in 163 cases].
AB  - OBJECTIVE: To evaluate the clinical value of supraglottic horizontal partial
      laryngectomy. METHODS: One hundred and sixty-three patients with supraglottic
      laryngeal carcinoma were treated surgically by supraglottic horizontal partial
      laryngectomy from 1978 to 1998. There were 64 males and 99 females. Five cases
      were staged I, 95 staged II, 48 staged III and 15 staged IV. The surgical
      techniques were improved: The hyoid was removed conventionally; The outer
      perichondrium of thyroid cartilage was turned into the laryngeal cavity and
      sutured with the mucosa of laryngeal ventricle and the base of tongue was sutured
      to the reserved thyroid cartilage. Survival was evaluated using the Kaplan-Meier
      method. The differences between stages were tested by Los-Rank method. RESULTS:
      The 5-year survival rate were 100.0%, 77.9%, 54.2% and 33.3% for patients staged
      I to IV respectively, and were statistically significant (P = 0.0006) between
      different clinical stages. The 5-year survival rate were 73.1% and 45.5% in
      patients with cN0 and cN + respectively, and were statistically significant (P =
      0.0132). The speech and swallowing functions were good after operation. The
      decannulation rate was 91.4%. The main causes of death were cervical lymph node
      metastasis in 40% (20/50) and laryngeal recurrence in 18% (9/50). The occult
      metastasis rate was 23.1% (30/130) and cervical metastasis rates of patients with
      cN1-3 75.8% (25/33), with a total metastasis rate was 33.7 (55/163). CONCLUSIONS:
      Supraglottic horizontal partial laryngectomy is very effective in eradicating
      disease and in preserving laryngeal function on condition that the indications
      were selected correctly. The selective lateral neck dissection was recommended
      for supraglottic carcinoma.

PMID- 17190424
TI  - [Effect analysis of surgery for treating abnormal styloid process].
AB  - OBJECTIVE: To analyze the relationship between pharyngeal paraesthesia and
      abnormal styloid process, and to evaluate the surgery outcome. METHODS: One
      hundred and four patients with styloid process abnormality, especially those with
      pharyngeal paraesthesia were studied preoperatively and postoperatively. RESULTS:
      Among 104 patients who complained about foreign body sensation of the pharynx and
      a sore throat, after partial removal of styloid process, 71.2% (74/104) cured
      (symptoms disappeared), 12.5% (13/104) improved, while 16.3% (17/104) had no
      improvement. The responding rate was 83.7% (87/104). CONCLUSIONS: Not all
      abnormality of styloid process subjects would have pharyngeal paraesthesia, so
      for this kind of cases a more comprehensive analysis is necessary. Surgery via
      mouth is preferable.

PMID- 17190426
TI  - [Clinical report of 81 cases of multiple primary cancers in laryngeal carcinoma].
AB  - OBJECTIVE: To explore the clinical characteristics and the survival status of the
      patients with laryngeal squamous cell carcinoma in the multiple primary cancers
      (MPC). METHODS: Follow-up and clinical data were analyzed retrospectively in 81
      laryngeal squamous cell cancer patients with MPC among 1101 patients with
      laryngeal carcinoma. Survival analysis and every influencing factor on survival
      rate were performed by Kaplan-Meier method. RESULTS: The occurrence rate of MPC
      in the patients with laryngeal squamous cell cancer was 7.4% (81/1101) in this
      report. Oral cavity carcinoma and nasopharyngeal carcinoma were the most common
      MPC in 29 cases (35.8%) in head and neck regions. MPC in head and neck regions
      were more often seen among patients who had treated with radiotherapy (chi2 =
      5.7, P = 0.017). Lung carcinoma (25.9%, 21/81) and esophageal carcinoma (22.2%,
      18/81) were the most common MPC in remote organs in 52 cases (64.2%). Thirty
      seven MPC cases (45.7%) were occurred in aerodigestive tract and 32 cases(39.5%)
      in respiratory tract in this series. Fourteen cases (17.3%) were synchronous MPC,
      the median time interval was 2 months. Other 67 cases (82.7%) were metachronous
      MPC, the median time interval was 28 months. The squamous cell carcinoma (66.7%)
      was the most common pathologic type among all MPC in 81 cases, which was more
      often seen among patients who had smoked and drunk (P = 0.007). The MPC of
      esophageal carcinoma and oropharyngeal carcinoma were more often seen among
      patients of supraglottic index cancer presentation (P = 0.04). The MPC of oral
      cavity cancers and nasopharyngeal carcinoma and lung carcinoma were more often
      seen among patients of glottic index cancer presentation (P = 0.006). The total
      three-and five-year survival rates were 45.2% and 29.7% respectively of all MPC
      patients, the five-year survival rate for patients (53 cases) who received
      actively different therapies for their MPC was 45.5%, obviously higher than that
      of untreated patients (28 cases) whose three-year survival rate was zero (P =
      0.000). CONCLUSIONS: Lung carcinoma and esophageal carcinoma were the most common
      multiple primary cancers among MPC of the laryngeal cancer. MPC of the laryngeal
      cancer in head and neck regions were more often seen among patients who had
      treated with radiotherapy. The pathologic type of squamous carcinomas of MPC was
      more often seen among patients who had smoked and drunk. MPC affected the
      prognosis of patients in laryngeal cancer largely. Treating effectively and in
      time could help to improve the survival rate of patients with MPC in laryngeal
      squamous cell carcinomas.

PMID- 17190427
TI  - [A case report of concha bullosa mucocele of the middle turbinate].

PMID- 17190429
TI  - [Quantitative analysis of epidermal growth factor receptor mRNA in laryngeal
      carcinoma by reverse transcription-real time polymerase chain reaction with
      TagMan probe].
AB  - OBJECTIVE: To establish a method of quantitative analysis of epidermal growth
      factor receptor(EGFR) mRNA in laryngeal carcinoma by reverse transcription-real
      time polymerase chain reaction with TagMan probe and evaluate its applicable
      value. METHODS: The technique of reverse transcription-real time polymerase chain
      reaction with highly specific primers and probe was applied. And with GAPDH as
      internal standard, EGFR mRNA in 32 laryngeal carcinoma tissues, compared with
      their own macroscopically normal laryngeal mucosa tissues adjacent to the tumors,
      were quantitatively examined. The recombinant plasmid of EGFR was constructed,
      and then sequenced. RESULTS: The recombinant plasmid of EGFR was successfully
      constructed. And the mRNA index of EGFR in 32 laryngeal carcinoma tissues in
      terms of M (QR) was 0.025 (0.076), which was higher than 0.008 (0.027) in their
      own macroscopically normal laryngeal mucosa tissues adjacent to the tumors, P
      value is 0. 007. CONCLUSIONS: The method of reverse transcription-real time
      polymerase chain reaction with TagMan probe is quite objective, precise and high
      throughput in the application for the mensuration of EGFR mRNA in laryngeal
      carcinoma.

PMID- 17190428
TI  - [Effects of glucocorticoid on tissue remodeling of nasal mucosa of chronic
      rhinosinusitis with nasal polyposis after endoscopic surgery].
AB  - OBJECTIVE: To evaluate the effects of glucocorticoid on tissue remodeling of
      nasal mucosa from patients with chronic rhinosinusitis with nasal polyposis
      (CRSwNP) after endoscopic surgery. METHODS: Nasal mucosa obtained from 30 cases
      of CRSwNP during nasal endoscopic surgery were considered as preoperation group.
      These patients were equally divided into two groups after surgery, ie.
      glucocorticoid group and contrast group. Uncinate process mucosa samples from 6
      patients during septoplasty were considered as normal control group. Epithelial
      damage and expressions of transforming growth factor-beta1 (TGF-beta1) and
      collagen III were studied by light microscopy and immunohistochemistry. RESULTS:
      In nasal mucosa samples of preoperation group, epithelial damage showed 90%
      (27/30) of stage 3 and 10% (3/30) of stage 2; TGF-beta1 positive cells and
      collagen III positive basement membrane with more than 20 microm were seen in 87%
      (26/30) and 97% (29/30) of samples, respectively. No significant difference was
      observed in morphology of nasal mucosa and expressions of TGF-beta1 and collagen
      III between glucocorticoid group and contrast group at 1th month after surgery.
      At 3th month after surgery, epithelial damage displayed 53% (8/15) of stage 3,
      33% (5/15) of stage 2 and 14% (2/15) of stage 1 in contrast group; however, 93%
      (14/15) of stage 0 and 7% (1/15) of stage 1 in glucocorticoid group. The
      difference of epithelial damage between two groups was significant (Uc = 4.481, P
      < 0.05). The amount of TGF-beta1 positive cell was markedly higher in contrast
      group than in glucocorticoid group (t = 2.32, P < 0.05). The thickness of
      basement membrane was above 20 microm in 67% of contrast group (10 cases) and 27%
      of glucocorticoid group (4 cases); the difference between the two groups was
      significant (P < 0.05). CONCLUSIONS: Tissue remodeling is present in nasal mucosa
      of CRSwNP after endoscopic surgery. Early and appropriate administration of
      glucocorticoid plays an important role in inhibition of tissue remodeling and
      prevention of relapse. Postoperative follow-up should not be less than 3 month.

PMID- 17190430
TI  - [Somatic mutations of mitochondrial DNA in thyroid papillary carcinoma].
AB  - OBJECTIVE: To analyze the somatic mutations in the D-loop of mtDNA and further
      evaluate the possibility of mitochondrial genetic instability in thyroid
      papillary carcinoma. METHODS: Hypervariable regions ( HVR-I and HVR-II) in the D
      loop of mtDNA from the specimen of 35 thyroid papillary cancers and matched
      lymphocytes were amplified by PCR, and then were sequenced. RESULTS: Comparing
      the sequences of tumors to those of matched lymphocytes and normal thyroid
      tissues, 5 somatic mutations in 2 patients (5.7%) were found. Two mutations were
      insertions of C in a poly-cytidine (nt303) microsatellite, and 3 at positions 73,
      152 and 194 in HVR-II. In addition, of the 294 genetic variants detected, 292
      were previously recorded polymorphisms, whereas 2 were new polymorphisms (nt324:C
      ->G, nt16092:T-->A). CONCLUSIONS: Mutations in the D-loop of mtDNA were found in
      thyroid papillary cancers, this mutation rate was lower than the reported rate of
      alteration in tumors of epithelial origin, and further work is required to
      elucidate the relationship between this mutations and the development of thyroid
      papillary carcinoma.

PMID- 17190432
TI  - [Nasal ventilation improvement after inferior turbinate fracture and partial
      removal with chisel].

PMID- 17190431
TI  - [Analysis of non-improving symptoms after endoscopic sinus surgery for chronic
      sinusitis].

PMID- 17190433
TI  - [Clinical characteristics of parathyroid lesions].

PMID- 17190434
TI  - [Treatment of dated closely laryngotracheal injury].

PMID- 17190435
TI  - [Tanabe tracheoesophageal shunt phonation after total laryngectomy].

PMID- 17190436
TI  - [Cervical lymph node metastasis of malignant fibrous histiocytoma of the
      hypopharynx].

PMID- 17190437
TI  - [Research progress in large vestibular aqueduct syndrome].

PMID- 17190438
TI  - [Hearing loss and cognitive disorder].

PMID- 17190440
TI  - Decaspirones F-I, bioactive secondary metabolites from the saprophytic fungus
      Helicoma viridis.
AB  - Decaspirones F-H (1-3), three new spirobisnaphthalene derivatives, and one new
      non-spirobisnaphthalene, decaspirone I (4), have been isolated from cultures of
      an isolate of the saprophytic fungus Helicoma viridis. The structures of these
      compounds were determined mainly by analysis of their NMR spectroscopic data. The
      absolute configuration of decaspirone F (1) was established by X-ray
      crystallographic analysis of its mono-bromobenzoate derivative. In standard disk
      assays, compounds 1-4 showed modest activity against Pseudomonas aeruginosa
      (multiple antibiotic-resistant strain, ATCC 27853), and decaspirone G (2) also
      displayed activity against Lactococcus lacti (PCM 2379).

PMID- 17190441
TI  - Hyrtiazepine, an azepino-indole-type alkaloid from the Red Sea marine sponge
      Hyrtios erectus.
AB  - Biological and chemical investigations of the methanolic crude extract of the Red
      Sea marine sponge Hyrtios erectus led to the isolation of a novel azepino-indole
      type alkaloid named hyrtiazepine (2) and 5-hydroxy-1H-indole-3-carboxylic acid
      methyl ester (3), together with the known metabolites hyrtiosulawesine (1), 5
      hydroxyindole-3-carbaldehyde (4), hyrtiosin A (5), and hyrtiosin B (6). Their
      structures were elucidated on the basis of mass spectrometry and detailed 2D NMR
      spectroscopic data. Hyrtiosulawesine (1) displayed a significant
      antiphospholipase A2 activity with an IC50 value of 14 microM in a fluorometric
      assay using Crotalus adamanteus venom phospholipase A2.

PMID- 17190439
TI  - Decaspirones A-E, bioactive spirodioxynaphthalenes from the freshwater aquatic
      fungus Decaisnella thyridioides.
AB  - Decaspirones A-E (1-5), five new compounds related to the palmarumycins, were
      isolated from cultures of the freshwater aquatic fungal species Decaisnella
      thyridioides. The known compound palmarumycin CP1 (6) was also obtained. The
      structures of 1-5 were determined by analysis of NMR and MS data, and their
      relative configurations were assigned by analysis of 1H NMR J-values and NOESY
      data. The structure of the lead compound 1 was confirmed by X-ray
      crystallographic analysis. Compounds 1-5 possess a trans ring fusion not
      previously reported in members of this structural class. The absolute
      configuration of 1 was assigned using the modified Mosher method. Compounds 1-5
      showed potent antifungal and antibacterial activity.

PMID- 17190442
TI  - Cytotoxic oxygenated triterpenoid saponins from Symplocos chinensis.
AB  - A n-butanol-soluble fraction of an ethanolic extract from the roots of Symplocos
      chinensis showed cytotoxic activity against several cancer cell lines. Bioassay
      guided purification led to the isolation and characterization of eight new
      triterpenoid saponins, symplocososides L-S (1-8). The structures of 1-8 were
      elucidated as glycosides based on oxygenated aglycons by spectroscopic and
      chemical methods. These compounds and their hydrolytic products, along with some
      additional analogues obtained earlier from S. chinensis roots, were evaluated for
      cytotoxicity in a small cancer cell panel.

PMID- 17190443
TI  - Antihyperglycemic activity and chemical constituents of Eysenhardtia platycarpa.
AB  - The methanolic extracts from branches (BEP) and leaves (LEP) of Eysenhardtia
      platycarpa significantly decreased the blood glucose levels in normal and
      streptozotocin (STZ)-induced diabetic rats. One new flavone, (1"R)-5,4',1"
      trihydroxy-6,7-(3",3"-dimethylchroman)flavone (1), together with the known
      compounds 5,7-dihydroxy-6-methyl-8-prenylflavanone (3), 5,7-dihydroxy-8-methyl-6
      prenylflavanone (4), 5,7-dihydroxy-6-prenylflavanone (5), 5,7-dihydroxy-8
      prenylflavanone (6), 3-O-acetyloleanolic acid (7), oleanolic acid, 3beta-acetoxy
      11alpha,12alpha-epoxy-oleanan-28,13beta-olide, lupeol, betulinic acid, beta
      sitosterol, beta-sitosteryl beta-D-glucopyranoside, beta-sitosteryl palmitate,
      and 3-O-methyl-myo-inositol were isolated from BEP. Additionally, one new
      flavanone, (2S)-4'-O-methyl-6-methyl-8-prenylnaringenin (2), as well as the known
      compounds 3, 4, 6, 4'-O-methyl-8-prenylnaringenin (8), and 5-hydroxy-7-methoxy-8
      prenylflavanone (9) were isolated from LEP. 3-O-Acetyloleanolic acid (7),
      identified as the major constituent of BEP, showed a significant decrease (31
      mg/kg of body weight, P < 0.05) in the glucose level of STZ-induced diabetic
      rats. The obtained results correlate with the traditional use of this species.

PMID- 17190444
TI  - Anti-inflammatory, anti-tumor-promoting, and cytotoxic activities of constituents
      of marigold (Calendula officinalis) flowers.
AB  - Ten oleanane-type triterpene glycosides, 1-10, including four new compounds,
      calendulaglycoside A 6'-O-methyl ester (2), calendulaglycoside A 6'-O-n-butyl
      ester (3), calendulaglycoside B 6'-O-n-butyl ester (5), and calendulaglycoside C
      6'-O-n-butyl ester (8), along with five known flavonol glycosides, 11-15, were
      isolated from the flowers of marigold (Calendula officinalis). Upon evaluation of
      compounds 1-9 for inhibitory activity against 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds,
      except for 1, exhibited marked anti-inflammatory activity, with ID50 values of
      0.05-0.20 mg per ear. In addition, when 1-15 were evaluated against the Epstein
      Barr virus early antigen (EBV-EA) activation induced by TPA, compounds 1-10
      exhibited moderate inhibitory effects (IC50 values of 471-487 mol ratio/32 pmol
      TPA). Furthermore, upon evaluation of the cytotoxic activity against human cancer
      cell lines in vitro in the NCI Developmental Therapeutics Program, two triterpene
      glycosides, 9 and 10, exhibited their most potent cytotoxic effects against colon
      cancer, leukemia, and melanoma cells.

PMID- 17190445
TI  - Rubrisandrins A and B, lignans and related anti-HIV compounds from Schisandra
      rubriflora.
AB  - Bioactivity-directed fractionation of an ethanolic extract of the fruits of
      Schisandra rubriflora led to the isolation and identification of
      dibenzocyclooctadiene lignans including the new lignans rubrisandrins A (1a + 1b)
      and B (2) and the known lignans gomisin J (3), (+/-)-gomisin M1 (4), (+)-gomisin
      M2 (5), schisanhenol (6), deoxyschisandrin, schisantherin B, schisandrin,
      tigloylgomisin P, gomisin O, angeloylgomisin P, and epigomisin O. Their structure
      and stereochemistry were determined by spectroscopic methods, including 2D-NMR
      techniques. Compounds 1 and 3-6 were active as anti-HIV agents. (+/-)-Gomisin M1
      (4) exhibited the most potent anti-HIV activity, with EC50 and therapeutic index
      (TI) values of <0.65 microM and >68, respectively.

PMID- 17190446
TI  - Engineering of the spinosyn PKS: directing starter unit incorporation.
AB  - The spinosyns are a family of potent and highly selective insect control agents
      that display a favorable environmental profile. As some regions of the spinosyn
      molecule are recalcitrant to chemical modification, a targeted genetic approach
      was carried out to generate new analogues. The polyketide synthase (PKS) loading
      modules from the avermectin PKS of Streptomyces avermitilis and the erythromcyin
      PKS of Saccharopolyspora erythraea were each used to replace the spinosyn PKS
      loading module. Both of the resulting strains containing hybrid PKS pathways
      produced the anticipated spinosyn analogues. Supplementation of the culture media
      with a range of exogenous carboxylic acids led to the successful incorporation of
      these novel elements to yield further novel spinosyn molecules, some of which
      demonstrated potent and new insecticidal activities. Furthermore, it has been
      demonstrated that semisynthesis of such novel metabolites can then be used to
      generate active analogues, demonstrating the effectiveness of utilizing these
      complementary methods to search the chemical space around this template.

PMID- 17190447
TI  - seco-Cycloartane triterpenes from Gardenia aubryi.
AB  - Three new 3,4-seco-cycloartanes, secaubryenol (1), secaubrytriol (2), and
      secaubryolide (3), were isolated from an exudate collected on the aerial parts of
      Gardenia aubryi, in addition to the known (24S)-cycloartane-24,25-diol-3-one,
      coccinetane A, herbacetin 3,8-dimethyl ether, hibiscetin 3,8,3',4'-tetramethyl
      ether, and conyzatin. The structures of 1 and 2 were established by mass
      spectrometry and NMR experiments, while the relative configuration of 2 was
      defined unequivocally using X-ray crystallography. The in vitro cytotoxic
      activity of compounds 1-3 was evaluated against four human solid tumor cell
      lines.

PMID- 17190449
TI  - Bioactive compounds from the gorgonian Briareum polyanthes. Correction of the
      structures of four asbestinane-type diterpenes.
AB  - Our extended chemical investigation of the crude MeOH-CHCl3 extract of the
      gorgonian octocoral Briareum polyanthes from Puerto Rico has led to the isolation
      of three eunicellin-type diterpenoids, 1-3, along with five (4-8) diterpenoids of
      the asbestinane-type and one (9) of the briarane-type of polycyclized diterpenes.
      The structures and relative stereochemistry of the new compounds 1-9 were
      established on the basis of spectroscopic analysis (1H NMR, 13C NMR, HMQC, HMBC,
      NOESY). The biological activity of these compounds against pathogenic microbes
      responsible for various human infectious diseases was investigated. In addition,
      new data recorded for four known asbestinin diterpenes also isolated during this
      investigation and further analysis through chemical reactions have prompted us to
      revise our original structural assignments for these compounds.

PMID- 17190450
TI  - Cytotoxic styryl-lactones from the leaves and twigs of Polyalthia crassa.
AB  - Four new styryl-lactones, crassalactones A-D (1-4), were isolated from a
      cytotoxic ethyl acetate-soluble extract of the leaves and twigs of Polyalthia
      crassa, together with seven known compounds, (+)-3-acetylaltholactone, (+)
      altholactone, aristolactam AII, cinnamic acid, (+)-goniofufurone, (+)
      goniopypyrone, and (+)-howiinol A. Their structures were determined on the basis
      of spectroscopic methods. The absolute configuration of 1-3 was established by
      chemical conversions. Single-crystal X-ray analysis and the Mosher ester method
      were used to confirm the absolute stereochemistry of 4. Cytotoxic evaluation
      against several mammalian cancer cell lines was performed on all new isolates,
      aristolactam AII, and the modified (+)-tricinnamate derivative 11 obtained from
      1.

PMID- 17190448
TI  - Sodwanone and yardenone triterpenes from a South African species of the marine
      sponge Axinella inhibit hypoxia-inducible factor-1 (HIF-1) activation in both
      breast and prostate tumor cells.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that promotes tumor
      cell adaptation and survival under hypoxic conditions. HIF-1 is currently
      recognized as an important molecular target for anticancer drug discovery. A T47D
      breast tumor cell-based reporter assay was used to evaluate the NCI Open
      Repository of marine invertebrates and algae lipid extracts for HIF-1 inhibitory
      activity. Bioassay-guided fractionation and isolation of an active extract from
      Axinella sp. yielded seven new sodwanone triterpenoids [3-epi-sodwanone K (1), 3
      epi-sodwanone K 3-acetate (2), 10,11-dihydrosodwanone B (4), sodwanones T-W (3,
      7, 8, 9)], the new yardenone triterpene 12R-hydroxyyardenone (10), and the
      previously reported compounds sodwanone A (5), sodwanone B (6), and yardenone
      (11). The structures and relative configurations of these Axinella metabolites
      were determined spectroscopically. The absolute configuration of 1 was determined
      by the modified Mosher ester procedure. Sodwanone V (8) inhibited both hypoxia
      induced and iron chelator (1,10-phenanthroline)-induced HIF-1 activation in T47D
      breast tumor cells (IC50 15 microM), and 8 was the only sodwanone that inhibited
      HIF-1 activation in PC-3 prostate tumor cells (IC50 15 microM). Compounds 1, 3,
      4, and 5 inhibited hypoxia-induced HIF-1 activation in T47D cells (IC50 values 20
      25 microM). Compound 2 was cytotoxic to T47D cells (IC50 22 microM), and 8 showed
      cytotoxicity to MDA-MB-231 breast tumor cells (IC50 23 microM).

PMID- 17190451
TI  - Clerodane diterpenoids from Salvia splendens.
AB  - Four new clerodane diterpenoids, salvisplendins A-D (1-4), have been isolated
      from an acetone extract of the flowers of Salvia splendens, together with an
      artifact (5), arising from salvisplendin D (4) by addition of diazomethane, and
      the already known clerodane olearin (6). The structures of the new compounds (1
      5) were established mainly by 1D and 2D NMR spectroscopic studies and, in the
      case of salvisplendin A (1), by chemical correlation with splenolide B (7).
      Complete 1H and 13C NMR assignments for olearin (6), not published hitherto, are
      also reported.

PMID- 17190452
TI  - Cyclic heptapeptides from the Jamaican sponge Stylissa caribica.
AB  - Two new cyclic heptapeptides, stylisin 1(1) and stylisin 2 (2), were isolated and
      characterized from the Jamaican sponge Stylissa caribica, in addition to the
      cyclic heptapeptide phakellistatin 13 (3) and the known bromopyrrole alkaloids
      sceptrin (4), stevensine (5), and oroidin (6). The new structures were assigned
      on the basis of 1D and 2D NMR spectroscopic data, as well as chemical methods for
      the elucidation of the absolute configuration of amino acids. The peptides and
      alkaloids have been evaluated for their antimicrobial, antimalarial, anticancer,
      anti-HIV-1, anti-Mtb, and antiinflammatory activities.

PMID- 17190454
TI  - Cembrane diterpenes from the gorgonian Lophogorgia peruana.
AB  - The chemical study of the gorgonian Lophogorgia peruana collected at the Gulf of
      California has led to the isolation of the new diterpenes lophodienone (2),
      lophodiol A (3), lophodiol B (4), 17-acetoxylophotoxin (5), 15,16-epoxylophotoxin
      (6), 17-acetoxy-15,16-epoxylophotoxin (7), and isoepoxylophodione (8), together
      with the known compounds lophotoxin (1), rubifolide (9), lopholide (10),
      deoxylophotoxin (11), and the lophotoxin analogues 12 and 13. The structures of
      the new metabolites have been established by spectroscopic techniques and
      chemical correlation. The in vitro cytotoxicity has been tested against three
      tumor cell lines.

PMID- 17190455
TI  - Daryamides A-C, weakly cytotoxic polyketides from a marine-derived actinomycete
      of the genus Streptomyces strain CNQ-085.
AB  - In the course of our continuing search for new antitumor-antibiotics from marine
      derived actinomycete bacteria, four new cytotoxic compounds, designated as
      daryamides A (1), B (2), and C (3) and (2E,4E)-7-methylocta-2,4-dienoic acid
      amide (4), were isolated from the culture broth of a marine-derived Streptomyces
      strain CNQ-085. The structures of these new compounds were assigned by detailed
      interpretation of spectroscopic data. The relative configuration of 1 was
      determined by comprehensive NMR analysis, while the absolute configuration of 1
      was determined as 4S,5R using the modified Mosher method. The daryamides show
      weak to moderate cytotoxic activity against the human colon carcinoma cell line
      HCT-116 and very weak antifungal activities against Candida albicans.

PMID- 17190453
TI  - Yuzurimine-type alkaloids from Daphniphyllum yunnanense.
AB  - Five new yuzurimine-type alkaloids, yunnandaphnines A-E (2-6), together with two
      known analogues, macrodaphniphyllamine (1) and calycinine A (7), have been
      isolated from the leaves and twigs of Daphniphyllum yunnanense. The structures of
      the new alkaloids were elucidated by spectroscopic methods. Yunnandaphnine E (6)
      is a novel heptacyclic yuzurimine-type alkaloid with an oxazine ring.

PMID- 17190456
TI  - 26,27-cyclosterols and other polyoxygenated sterols from a marine sponge
      Topsentia sp.
AB  - Thirty sterols (1-30) were isolated from bioactive fractions of a marine sponge
      Topsentia sp., of which 16 were new (1, 2, 8, 10-14, 16, 17, 19, 21, 24, 25, 27,
      and 30). They were characterized as sterols with 10 different side chains and as
      having various functionalities including 5alpha,8alpha-epidioxy (1-9),
      5alpha,6alpha-epoxy-7-ol (10-15), 5,8-dien-7-one (24-28), 5-en-3beta-ol (29), and
      1(10-->6)abeo-5,7,9-triene-3alpha,11alpha-diol (30) units and included
      polyoxygenated sterols (16-23). One of the key features of these new sterols is
      the presence of the (24R,25R,27R)-26,27-cyclo-24,27-dimethylcholestane side
      chain, whose absolute stereochemistry was defined by an acid-catalyzed ring
      opening method and by comparison with the four synthetic isomers of known
      absolute stereochemistry. The occurrence of several known fungal sterols and
      relevant new sterols in this sponge suggested their possible origin from
      symbiotic fungi. Selected compounds were tested against a panel of five human
      solid tumor cell lines and displayed moderate to marginal cytotoxicity.

PMID- 17190458
TI  - Low-abundance kutznerides from Kutzneria sp. 744.
AB  - Five new (5-9) and four known (1-4) kutznerides were isolated from the
      actinomycete Kutzneria sp. 744. Compounds 1-9 all consisted of a
      cyclohexadepsipeptide core with the general structure 2-(1-methylcyclopropyl)-D
      glycine-(2S,3aR,8aS)-6,7-dichloro-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3
      b]indole-2-carboxylic acid-3-hydroxy-D-glutamic acid-O-methyl-L-serine-L
      piperazic acid-(S)-2-hydroxy-3,3-dimethylbutyric acid. Compounds 5, 6, and 8
      contained erythro-3-hydroxy-D-glutamic acid, whereas 7 and 9 contained the threo
      isomer and the hydroxy acid was present as (S)-2-hydroxy-3-methylbutyric acid in
      5 and 7. The piperazic acid was C-5-N unsaturated and 4-hydroxylated in 6, 4
      chlorinated in 8, and C-5-N unsaturated in 9. Minimal inhibitory concentrations
      for bacteria were found down to 6 microM (Staphylococcus aureus and Erwinia
      carotovora) and for fungi down to 70 microM (Fusarium culmorum). The
      trichlorinated 2 and 8 showed the highest antimicrobial activity, whereas 6, with
      a hydroxylated piperazic acid unit, did not show any inhibition of the pathogens
      at 230 microM.

PMID- 17190457
TI  - Cytotoxic flavaglines and bisamides from Aglaia edulis.
AB  - Two new cyclopenta[b]benzofurans, aglaroxin A 1-O-acetate (2) and 3'
      methoxyaglaroxin A 1-O-acetate (3), a new benzo[b]oxepine, 19,20-dehydroedulisone
      A (4), and five new cyclopenta[bc]benzopyrans, edulirin A (5), edulirin A 10-O
      acetate (6), 19,20-dehydroedulirin A (7), isoedulirin A (8), and edulirin B (9),
      were isolated from the bark of Aglaia edulis, along with one known
      cyclopenta[b]benzofuran, aglaroxin A (1). Additionally, four new amides,
      aglamides A-D (10-13), as well as three known compounds, aglalactone, scopoletin,
      and 5-hydroxy-3,6,7,4'-tetramethoxyflavone, were isolated from the leaves and/or
      twigs of this species. The structures of the new compounds (2-13) were elucidated
      by interpretation of their spectroscopic data. All isolates obtained in this
      study were evaluated for cytotoxicity against both several human cancer cell
      lines (Lu1, LNCaP, and MCF-7) and a nontumorigenic (HUVEC) cell line. Among these
      isolates, the cyclopenta[b]benzofurans (1-3) exhibited potent in vitro cytotoxic
      activity (ED50 range 0.001 to 0.8 microg/mL). Aglaroxin A 1-O-acetate (2) was
      further evaluated in the in vivo P388 lymphocytic leukemia model, by
      intraperitoneal injection, but found to be inactive in this model.

PMID- 17190459
TI  - Neo-clerodane diterpenes from the hallucinogenic sage Salvia divinorum.
AB  - Seven new neo-clerodane diterpenes, salvidivins A (2), B, (3), C (4), and D (5),
      salvinorins H (6) and I (7), and divinatorin [corrected] F (8), along with eight
      known neo-clerodane diterpenes, salvinorins A (1)-F, divinatorins A and B, and
      seven other constituents, were isolated from the hallucinogenic sage Salvia
      divinorum. The structures of 1-7 were elucidated on the basis of 2D NMR
      spectroscopic studies.

PMID- 17190460
TI  - Sulfated alkenes from the echinus Temnopleurus hardwickii.
AB  - Three new sulfated alkenes (1-3), trimethylammonium (5R)-5,9-dimethyl-(3E)-3,8
      decadienyl-1-sulfate, dimethylammonium (5R)-5,9-dimethyl-(3E)-3,8-decadienyl-1
      sulfate, and 2'-methyl-4'-oxobutan-2-ylammonium (5R)-5,9-dimethyl-(3E)-3,8
      decadienyl-1-sulfate, were isolated from an echinoderm, Temnopleurus hardwickii.
      Their structures were elucidated by spectral analysis and chemical degradation
      methods.

PMID- 17190461
TI  - Ashwagandhanolide, a bioactive dimeric thiowithanolide isolated from the roots of
      Withania somnifera.
AB  - A new dimeric withanolide, ashwagandhanolide (1), was isolated from the roots of
      an Ayurvedic medicinal herb, Withania somnifera. A detailed spectroscopic
      evaluation revealed its identity as a dimer with an unusual thioether linkage.
      Compound 1 displayed growth inhibition against human gastric (AGS), breast (MCF
      7), central nervous system (SF-268), colon (HCT-116), and lung (NCI H460) cancer
      cell lines, with IC50 values in the range 0.43-1.48 microg/mL. In addition, it
      inhibited lipid peroxidation and the activity of the enzyme cyclooxygenase-2 in
      vitro.

PMID- 17190462
TI  - Absolute configuration of sporotricale and structure of 6-hydroxysporotricale.
AB  - The absolute configuration of the two stereocenters of (+)-sporotricale (2a), a
      bioactive phthalide secondary metabolite, was determined through circular
      dichroism and by applying Mosher's method. The structure of 6-hydroxysporotricale
      (2c), isolated from cultures in vitro of Sporotrichum laxum, was also elucidated.

PMID- 17190463
TI  - Cucurbitane triterpenes from the fruiting bodies and cultivated mycelia of
      Leucopaxillus gentianeus.
AB  - A reinvestigation of the fruiting bodies of the mushroom Leucopaxillus
      gentianeus, allowed the isolation of two minor cucurbitane triterpenes, namely,
      cucurbitacin D (5) and the new metabolite 16-deoxycucurbitacin B (6). The latter
      compound lacks an oxygenated substituent at C-16, an unprecedented structural
      feature among congeners of cucurbitacin B. The cucurbitanes present in the
      fruiting bodies were compared with those extracted from mycelia grown on the
      modified Melin-Norkans (MMN) culture medium. Cucurbitacins B (1) and D (5), as
      well as leucopaxillones A (3) and B (4), were isolated from both sources; in
      contrast, 16-deoxycucurbitacin B (6) and a mixture of fatty acid esters of
      cucurbitacin B (2) were absent in the mycelia. A new triterpene, 18
      deoxyleucopaxillone A (7), was isolated from the mycelia, but was not detected in
      the fruiting bodies. The antiproliferative activity of the isolated triterpenes
      was determined against the NCI-H460 human tumor cell line, in comparison with the
      antitumor compound topotecan, a well-known topoisomerase I inhibitor.

PMID- 17190464
TI  - Bioactive oligostilbenoids from the stem bark of Hopea exalata.
AB  - Hopeanolin (1), an unusual resveratral trimer with an ortho-quinone nucleus, was
      isolated and characterized from the stem bark of Hopea exalata. Also obtained
      were six known stibenoids, shoreaphenol (2), vaticanol G (3), alpha-viniferin
      (4), pauciflorol A (5), vaticanol A (6), and trans-3,5,4'-trihydroxystilbene 2-C
      glucoside (7). The structure of 1 was determined by spectroscopic data
      interpretation. Compounds 1-7 were tested for antifungal activity and inhibitory
      effects against jack bean urease. Hopeanolin (1) demonstrated antifungal activity
      in the MIC value range 0.1-22.5 microg/mL.

PMID- 17190465
TI  - Abietane diterpenoids from Salvia pachyphylla and S. clevelandii with cytotoxic
      activity against human cancer cell lines.
AB  - A phytochemical study has been carried out on the aerial parts of Salvia
      pachyphylla and S. clevelandii. From S. pachyphylla, the known diterpenes
      carnosol (2), rosmanol, 20-deoxocarnosol (3), carnosic acid, isorosmanol (4), 7
      methoxyrosmanol, 5,6-didehydro-O-methylsugiol (5), 8beta-hydroxy-9(11),13
      abietadien-12-one (6), 11,12-dioxoabieta-8,13-diene, and 11,12-dihydroxy-20
      norabieta-5(10),8,11,13-tetraen-1-one were isolated, together with the new
      diterpene pachyphyllone (1). From S. clevelandii, the known diterpenes rosmadial
      (7), 16-hydroxycarnosol (8), abieta-8,11,13-triene, and taxodone were obtained,
      together with carnosol (2), rosmanol, and carnosic acid. The structure of the new
      compound (1) was identified on the basis of spectroscopic data analysis. Several
      of these compounds (1-8) were evaluated against a small panel of human cancer
      cell lines.

PMID- 17190466
TI  - A sorbicillinoid urea from an intertidal Paecilomyces marquandii.
AB  - A ureido Diels-Alder adduct of sorbicillinol 3 has been isolated from an
      intertidal marine Paecilomyces marquandii strain, in a screening for new natural
      products. The structure was determined by spectroscopic methods, and the relative
      stereochemistry was confirmed by molecular modeling. The absolute stereochemistry
      was deduced by comparison of the CD curves with those of known members of the
      bisorbicillinol family. This is the first report of the isolation of a ureido
      sorbicillinol derivative.

PMID- 17190467
TI  - Chloro- and bromophenols from cultures of Mycena alcalina.
AB  - Three new chlorinated phenols have been isolated from mycelial cultures of the
      mushroom Mycena alcalina. Their structures were determined by mass spectrometry
      and 1D and 2D NMR experiments. Addition of bromide to the medium resulted in the
      production of the corresponding brominated phenols. In addition, small amounts of
      the nonhalogenated precursor were also isolated, indicating that the halogenated
      metabolites are generated by a regioselectively operating halogenase.

PMID- 17190468
TI  - Taxoids from Taxus chinensis.
AB  - Two new taxoids, 13,15-epoxy-13-epi-taxayunnasin A (1) and taxchinin N (2), were
      isolated from the leaves and stems of Taxus chinensis. Compound 2 is the first
      taxoid to be reported with an alpha,beta-unsaturated lactone at C-4, C-5, C-20,
      and C-2. The structure of 1 was elucidated by spectroscopic analysis and
      confirmed by semisynthesis from taxayunnasin A, while 2 was determined
      structurally using spectroscopic methods and by single-crystal X-ray diffraction.

PMID- 17190469
TI  - Bionectins A-C, epidithiodioxopiperazines with anti-MRSA activity, from Bionectra
      byssicola F120.
AB  - Three new epidithiodioxopiperazine compounds, bionectins A (1), B (2), and C (3),
      along with a known compound, verticillin D (4), have been isolated from the
      mycelium of liquid fermentation cultures of the fungus Bionectra byssicola F120.
      The structures of compounds 1-3 were assigned on the basis of MS and NMR data.
      Compounds 1 and 2 incorporate a dioxopiperazine moiety with a disulfide bridge in
      their molecules, while 3 contains a dioxopiperazine ring with two methylsulfanyl
      groups. Compounds 1 and 2 exhibited antibacterial activity against S. aureus
      including methicillin-resistant S. aureus (MRSA) and quinolone-resistant S.
      aureus (QRSA), with MIC values of 10-30 microg/mL, while 3 showed no
      antibacterial activity even at 100 microg/mL.

PMID- 17190470
TI  - Zinagrandinolides A-C, cytotoxic delta-elemanolide-type sesquiterpene lactones
      from Zinnia grandiflora.
AB  - Three new delta-elemanolide-type sesquiterpene lactones, zinagrandinolides A-C (1
      3), and the known delta-elemanolide 4 have been isolated by a bioassay-guided
      fractionation of a cytotoxic hexane extract of the aerial parts of Zinnia
      grandiflora. The structures of 1-3 were determined on the basis of high
      resolution mass and NMR data. All compounds exhibited strong cytotoxicity against
      the cancer cell lines NCI-H460, MCF-7, SF-268, and MIA Pa Ca-2 and the normal
      human fibroblast cell type WI-38, but none showed significant selectivity.

PMID- 17190471
TI  - Major carotenoid isolated from Paracoccus schoinia NBRC 100637T is adonixanthin
      diglucoside.
AB  - The structure of a novel major carotenoid glycoside (nearly 80% of total
      carotenoids) from a newly isolated bacterium, Paracoccus schoinia NBRC 100637T,
      was determined to be adonixanthin diglucoside using spectral data. By contrast,
      carotenoid diglycosides are rare and are usually minor carotenoids in nature. The
      minor carotenoids in this bacterium included astaxanthin diglucoside, zeaxanthin
      diglucoside, canthaxanthin, echinenone, zeaxanthin, beta-cryptoxanthin, and beta
      carotene.

PMID- 17190472
TI  - Cacalol derivatives from Roldana angulifolia.
AB  - Four new modified eremophilanes, angulifolide (1) and angulifolins A-C (2-4), and
      two new triacetylglucosides (7 and 8) were isolated from Roldana angulifolia,
      together with several known compounds. The structures of the new compounds were
      elucidated by spectroscopic analysis and chemical reactions. The absolute
      configuration of compounds 2 and 3 was established by Mosher ester methodology.
      Cytotoxicity against selected human cancer cell lines was determined for the more
      abundant isolated metabolites.

PMID- 17190473
TI  - Xenofuranones A and B: phenylpyruvate dimers from Xenorhabdus szentirmaii.
AB  - Xenofuranones A (1) and B (2) have been isolated from cultures of the insect
      pathogenic bacterium Xenorhabdus szentirmaii, and their structures were
      elucidated by NMR and mass spectroscopy. Both compounds show similarities to
      fungal furanones, and their biosynthesis was studied using a reversed approach by
      feeding putative 12C precursors to an overall 13C background in small-scale
      experiments followed by gas chromatographic analysis coupled to mass
      spectrometry.

PMID- 17190476
TI  - Humidity-dependent wetting properties of high hysteresis surfaces.
AB  - The advancing contact angle (thetaadv) of water on thin films ( approximately 1
      microm) of poly(ethylene glycol) (PEG) with fluoroalkyl endgroups (6 kg/mol PEG
      with 10-carbon fluoroalkyl, denoted 6KC10) changes strongly with relative
      humidity (RH). Films of 6KC10 on silicon wafers pretreated with a fluorinated
      alkylsilane (TFOS) display thetaadv increasing from 75 degrees at 12% RH to 95
      degrees at 94% RH. The surprising transition to nonwetting character at high
      humidity is attributed to fluoroalkyl groups ordering at the air-hydrogel
      interface when they are liberated by dissolution of PEG crystallites above 85%
      RH. When water is withdrawn from a drop on 6KC10, the contact line does not
      recede. This extreme hysteresis is attributed to restructuring of the gel to bury
      the fluoroalkyl groups when in contact with water.

PMID- 17190474
TI  - Oppositines A and B, sesquiterpene pyridine alkaloids from a Sri Lankan
      Pleurostylia opposita.
AB  - Two new sesquiterpene pyridine alkaloids, oppositines A (1) and B (2), have been
      isolated from the plant Pleurostylia opposita, collected in Sri Lanka. The
      compounds were isolated and purified by solvent/solvent partitioning, column
      chromatography, and HPLC. Their structures were assigned on the basis of
      extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Oppositines A (1)
      and B (2) showed moderate cytotoxicity against HCT116 cell lines with EC50 values
      of 27 +/- 2 and 26 +/- 3 microM, respectively.

PMID- 17190477
TI  - pH- and thermosensitive polyaniline colloidal particles prepared by enzymatic
      polymerization.
AB  - Polyaniline colloids were prepared by enzymatic polymerization using chitosan and
      poly(N-isopropylacrylamide) as steric stabilizers. The resulting nanoparticles
      undergo flocculation by changing the pH or temperature of the aqueous
      dispersions. The environmentally responsive behavior of these colloids contrasts
      with that of polyaniline colloids synthesized using poly(vinyl alcohol) as the
      steric stabilizer. The colloid size was a function of the steric stabilizers and
      ranged from approximately 50 nm for polyaniline particles prepared in the
      presence of chitosan and partially hydrolyzed poly(vinyl alcohol) up to 350 nm
      for the particles synthesized using poly(N-isopropylacrylamide). UV-visible and
      Fourier transform infrared spectroscopic studies indicate that polyaniline
      colloids are spectroscopically similar to those obtained by traditional
      dispersion polymerization of aniline by chemical oxidation. These polyaniline
      colloids have potential applications in thermochromic windows and smart fluids.

PMID- 17190478
TI  - Nonwettable thin films from hybrid polymer brushes can be hydrophilic.
AB  - Hybrid brushes composed of two liquid polymers, poly(dimethylsiloxane) (PDMS) and
      a highly branched ethoxylated polyethylenimine (EPEI), were synthesized on Si
      wafers by the "grafting to" method and by applying a combinatorial approach
      (fabrication of gradient brushes). The combinatorial approach revealed a strong
      effect of "layer assisted tethering", which allowed us to synthesize hybrid
      brushes twice as thick as the reference homopolymer brushes. The hybrid brushes
      are stable thin films that can rapidly and reversibly switch between hydrophilic
      and hydrophobic states in water and air, respectively. The switching in water
      affects a rapid release of amino functional groups which can be used to regulate
      adhesion and reactivity of the material. The switching in air rapidly returns the
      brush to a hydrophobic state. The hybrid brush is hydrophilic because of two
      mechanisms: (1) exposure of EPEI chains to the brush-water interface under water,
      and (2) retention of some fraction of water via swollen EPEI chains (the EPEI
      chains swell by 2-3 times), which are conserved by a PDMS cap in air. The hybrid
      brush is wettable under water, and at the same time, the brush is nonwettable in
      air because water droplets are trapped in a metastable state when the water
      contact angle is above 90 degrees .

PMID- 17190480
TI  - Thermoresponsive reversible behavior of multistimuli pluronic-based pentablock
      copolymer at the air-water interface.
AB  - Surface behavior of the pH- and thermoresponsive amphiphilic ABCBA pentablock
      copolymer has been studied with respect to the environmental conditions. We
      demonstrate that the pentablock copolymer poly((diethylaminoethyl methacrylate)-b
      (ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)-b-(diethylaminoethyl
      methacrylate)) possesses reversible temperature changes at the air-water
      interface in a narrow pH range of the water subphase. Significant diversity in
      the surface morphology of pentablock copolymer monolayers at different pH and
      temperatures observed were related to the corresponding reorganization of central
      and terminal blocks. Remarkable reversible variations of the surface pressure
      observed for the Langmuir monolayers at pH 7.4 in the course of heating and
      cooling between 27 and 50 degrees C is associated with conformational
      transformations of terminal blocks crossing the phase line in the vicinity of the
      lower critical solution temperature point. The observed thermoresponsive surface
      behavior can be exploited for modeling of the corresponding behavior of
      pentablock copolymers adsorbed onto various biointerfaces for intracellular
      delivery for deeper understanding of stimuli-responsive transformations relevant
      to controlled drug and biomolecules release and retention.

PMID- 17190479
TI  - Nanostructure and transition of a strong polyelectrolyte brush at the air/water
      interface.
AB  - The strong polyelectrolyte layer in the monolayer of ionic amphiphilic diblock
      copolymers at the air/water interface consists of carpet and brush layers when
      the brush density is satisfactorily high like that of the weak acid polymer.
      Also, a drastic structural change was induced by the addition of salt to the
      brush layer. In this study, the critical brush density for the transition between
      "carpet-only" and "carpet + brush" structures for the strongly ionic amphiphilic
      diblock copolymer, poly(hydrogenated isoprepene)-b-poly(styrene sulfonic acid)
      sodium salt, monolayer was measured by an in situ X-ray reflectivity technique.
      The critical brush density was found to be about 0.12 nm-2, which is lower than
      that observed for a weak acid polymer and, unlike the weak acid polymer, is
      independent of the hydrophilic chain length. This difference might be attributed
      to the strong ionic nature of the brush chain. In addition, the reversibility of
      the transition was confirmed. The effect of salt addition to the nanostructure of
      the carpet layer was examined in detail. No structural change was found,
      indicating that most of the ionic groups in the carpet layer do not show an ionic
      nature because of counterion condensation.

PMID- 17190481
TI  - Switching surface chemistry with supramolecular machines.
AB  - Tethered supramolecular machines represent a new class of active self-assembled
      monolayers in which molecular configurations can be reversibly programmed using
      electrochemical stimuli. We are using these machines to address the chemistry of
      substrate surfaces for integrated microfluidic systems. Interactions between the
      tethered tetracationic cyclophane host cyclobis(paraquat-p-phenylene) and
      dissolved pi-electron-rich guest molecules, such as tetrathiafulvalene, have been
      reversibly switched by oxidative electrochemistry. The results demonstrate that
      surface-bound supramolecular machines can be programmed to adsorb or release
      appropriately designed solution species for manipulating surface chemistry.

PMID- 17190482
TI  - Effect of matrix elasticity on affinity binding and release of bioparticles.
      Elution of bound cells by temperature-induced shrinkage of the smart macroporous
      hydrogel.
AB  - The first step of bacterial or viral invasion is affinity and presumably
      multisite binding of bioparticles to an elastic matrix like a living tissue. We
      have demonstrated that model bioparticles such as inclusion bodies (spheres of
      about 1 microm in size) Escherichia coli cells (rods 1 x 3 microm), yeast cells
      (8 microm spheres), and synthetic microgel particles (0.4 microm spheres) are
      binding via different affinity interactions (IgG antibody-protein A, sugar
      lectin, and metal ion-chelate) to a macroporous hydrogel (MH) matrix bearing
      appropriate ligands. The elastic deformation of the MH results in the detachment
      of affinity bound bioparticles. The particle detachment on elastic deformation is
      believed to be due to multipoint attachment of the particles to affinity matrix
      and the disturbance of the distance between affinity ligands when the matrix is
      deformed. No release of affinity bound protein occurred on elastic deformation.
      The efficiency of the particle release by the elastic deformation depends on the
      density of the ligands at the particle surface as well as on the elasticity of
      the matrix for relatively large particles. The release of the particles occurred
      irrespectively of whether the deformation was caused by external forces
      (mechanical deformation) or internal forces (the shrinkage of thermosensitive
      macroporous poly-N-isopropylacrylamide hydrogel on increase in temperature).

PMID- 17190483
TI  - Synthesis and characterization of variable-architecture thermosensitive polymers
      for complexation with DNA.
AB  - Copolymers of N-isopropylacrylamide with a fluorescent probe monomer were grafted
      to branched poly(ethyleneimine) to generate polycations that exhibited lower
      critical solution temperature (LCST) behavior. The structures of these polymers
      were confirmed by spectroscopy, and their phase transitions before and after
      complexation with DNA were followed using ultraviolet and fluorescence
      spectroscopy and light scattering. Interactions with DNA were investigated by
      ethidium bromide displacement assays, while temperature-induced changes in
      structure of both polymers and polymer-DNA complexes were evaluated by
      fluorescence spectroscopy, dynamic light scattering, laser Doppler anemometry,
      and atomic force microscopy (AFM) in water and buffer solutions. The results
      showed that changes in polymer architecture were mirrored by variations in the
      architectures of the complexes and that the overall effect of the temperature
      mediated changes was dependent on the graft polymer architecture and content, as
      well as the solvent medium, concentrations, and stoichiometries of the complexes.
      Furthermore, AFM indicated subtle changes in polymer-DNA complexes at the
      microstructural level that could not be detected by light scattering techniques.
      Uniquely, variable-temperature aqueous-phase AFM was able to show that changes in
      the structures of these complexes were not uniform across a population of polymer
      DNA condensates, with isolated complexes compacting above LCST even though the
      sample as a whole showed a tendency for aggregation of complexes above LCST over
      time. These results indicate that sample heterogeneities can be accentuated in
      responsive polymer--DNA complexes through LCST-mediated changes--a factor that is
      likely to be important in cellular uptake and nucleic acid transport.

PMID- 17190485
TI  - In-situ investigation of the adsorption of globular model proteins on stimuli
      responsive binary polyelectrolyte brushes.
AB  - Binary brushes constituted from two incompatible polymers can be used in the form
      of ultrathin polymeric layers as a versatile tool for surface engineering to tune
      physicochemical surface characteristics such as wettability, surface charge,
      chemical composition, and morphology and furthermore to create responsive surface
      properties. Mixed brushes of oppositely charged weak polyelectrolytes represent a
      special case of responding surfaces that are sensitive to changes in the pH value
      of the aqueous environment and therefore represent interesting tools for
      biosurface engineering. The polyelectrolyte brushes used for this study were
      composed of two oppositely charged polyelelctrolytes poly(2-vinylpyridine) (P2VP)
      and poly(acrylic acid) (PAA). The in-situ properties and surface characteristics
      such as as surface charge, surface tension, and extent of swelling of these brush
      layers are functions of the pH value of the surrounding aqueous solution. To test
      the behavior of the mixed polylelctrolyte brushes in contact with biosystems,
      protein adsorption experiments with globular model proteins were performed at
      different pH values and salt concentrations (confinement of counterions) of the
      buffer solutions. The influence of the pH value, buffer salt concentration, and
      isoelectric points (IEP) of the brush and protein on the adsorbed amount and the
      interfacial tension during protein adsorption as well as the protein adsorption
      mechanism postulated in reference to recently developed theories of protein
      adsorption on polyelectrolyte brushes is discussed. In the salted regime, protein
      adsorption was found to be similar to the often-described adsorption at
      hydrophobic surfaces. However, in the osmotic regime the balance of electrostatic
      repulsion and a strong entropic driving force, "counterion release", was found to
      be the main influence on protein adsorption.

PMID- 17190484
TI  - Comparison of native extracellular matrix with adsorbed protein films using
      secondary ion mass spectrometry.
AB  - In the past decade, the temperature-responsive behavior of poly(N-isopropyl
      acrylamide) (pNIPAM) has come to be recognized as a convenient method for the
      nondestructive harvest of confluent cell layers. Recently, we have utilized this
      nondestructive cell harvest method as a means to ascertain the nature of the
      extracellular matrix (ECM) secreted from cells. In this work, we compare the ECM
      obtained after cell liftoff to individual ECM proteins adsorbed directly onto RF
      plasma-deposited pNIPAM (ppNIPAM). Using X-ray photoelectron spectroscopy, we
      find that the composition of ppNIPAM post-cell liftoff surfaces is consistent
      with those of the ppNIPAM post-protein adsorption surface, both of which differ
      from control surfaces. Using principal component analysis of positive-ion time-of
      flight secondary ion mass spectrometry (ToF-SIMS) data, we show that the major
      ECM proteins examined can effectively be identified from their amino acid
      compositions. By comparing the positive-ion ToF-SIMS data from each of the
      ppNIPAM post-protein adsorption surfaces to that of ppNIPAM post-cell liftoff, we
      find that ppNIPAM post-cell liftoff surfaces are distinctly separate from
      fibronectin (FN). This result is consistent with our previous observation using
      immunoassay that FN is clearly associated with the cell sheet after low
      temperature liftoff from ppNIPAM.

PMID- 17190486
TI  - Spectroscopic investigation of cationic comb-type copolymers/DNA interaction:
      interpolyelectrolyte complex enhancement synchronized with DNA hybridization.
AB  - We have demonstrated that cationic comb-type copolymers consisting of a
      polycation backbone and abundant grafts of water-soluble polymers stabilize DNA
      hybrids. Furthermore, the copolymers were found to accelerate strand exchange
      reaction between a double-stranded DNA and its complementary single-stranded DNA.
      In this article, we investigated the effects of PLL-g-Dex on base pairs of a self
      complementary DNA octamer, d(GGAATTCC). The soluble interpolyelectrolyte complex
      (IPEC) between the DNA and copolymer allowed us to characterize the complex by
      using spectroscopic methods under physiological ionic condition. Chemical shifts
      of nucleobase proton signals were not changed by PLL-g-Dex. Furthermore, the
      copolymer slightly changed the von't Hoff DeltaH accompanying the helix-coil
      transition of the octamer. These results indicated that the base pairs of the
      duplex DNA in the IPEC were not perturbed by the polycationic copolymer. It was
      obviously shown by temperature dependencies of proton and phosphorus NMR spectra
      that DNA/copolymer interaction was considerably enhanced in response to ds DNA
      formation. An increase in the density and total number of DNA negative charges
      upon hybrid formation likely caused the higher affinity of the copolymer with the
      ds form over that of the copolymer with the ss form. The IPEC formation of CCCs
      with DNA, however, seems highly sensitive to the coil-helix transition of the
      DNA.

PMID- 17190487
TI  - Role of stimuli-sensitive polymers in protein refolding: alpha-amylase and CcdB
      (controller of cell division or death B) as model proteins.
AB  - Alginate, a calcium-sensitive polymer, could carry out simultaneous purification
      and refolding of 8 M urea/100 mM dithiothreitol (DTT) denatured and thermally
      denatured alpha-amylase present in a commercial preparation. Activity recoveries
      of 80 and 70% in the former and the latter cases, respectively, were obtained.
      The fluorescence spectra showed refolding, and PAGE showed the absence of any
      aggregates in the refolded preparation. As another example, Eudragit S-100, a pH
      sensitive poly(methyl methacrylate), was used to refold CcdB (controller of cell
      division or death B) protein. Initial experiments with wild-type (WT) CcdB showed
      that Eudragit bound and precipitated (upon lowering the pH to 4.0) CcdB
      quantitatively from the latter's aqueous solution. The bioconjugate showed DNA
      gyrase inhibition activity of CcdB and could be recycled. The inclusion bodies of
      CcdB mutant CcdB-17P were solubilized in 8 M urea/100 mM dithiothreitol. This
      preparation could be refolded by precipitation with Eudragit. The fluorescence
      and CD spectra showed that protein refolding has occurred.

PMID- 17190488
TI  - Permeability and electrokinetic characterization of poly(ethylene terephthalate)
      capillary pore membranes with grafted temperature-responsive polymers.
AB  - Poly(ethylene terephthalate) (PET) track-etched membranes with average pore
      diameters of 692 and 1629 nm were functionalized using the monomer N
      isopropylacrylamide (NIPAAm) and a photoinitiated "grafting-from" approach in
      which a surface-selective reaction has been most efficiently achieved by
      combinations of the unmodified PET surface with benzophenone and, alternatively,
      of an aminated PET surface with benzophenone carboxylic acid. Consistent
      estimations of the pore diameters of the base PET membranes and of the effective
      grafted polyNIPAAm layer thicknesses on the PET pore walls were possible only on
      the basis of the permeabilities measured with aqueous solutions of higher ionic
      strength (e.g., 0.1 M NaCl). However, the permeabilities measured with ultrapure
      water indicated that the "electroviscous effect" was significant for both base
      membranes. The influences of membrane pore diameter, surface charge, and solution
      ionic strength could be interpreted in the framework of the space-charge model.
      Functionalized membranes with collapsed grafted polymer hydrogel layer
      thicknesses of a few nanometers exhibited almost zero values of the zeta
      potential estimated from the trans-membrane streaming potential measurements.
      This was caused by a "hydrodynamic screening" of surface charge by the neutral
      hydrogel. Very pronounced changes in permeability as a function of temperature
      were measured for PET membranes with grafted polyNIPAAm layers, and the effective
      layer thickness in the swollen state--here up to approximately 300 nm--correlated
      well with the degree of functionalization. The subtle additional effects of
      solution ionic strength on the hydrodynamic layer thickness at 25 degrees C were
      different from the effects for the base PET membranes and could be explained by a
      variation in the degree of swelling, resembling a "salting-out" effect. Overall,
      it had been demonstrated that the functionalized capillary pore membranes are
      well suited for a detailed and quantitative evaluation of the relationships
      between the synthesis, the structure, and the function of grafted stimuli
      responsive polymer layers.

PMID- 17190489
TI  - Design, synthesis, and aqueous aggregation behavior of nonionic single and
      multiple thermoresponsive polymers.
AB  - Nonionic water-soluble poly(acrylamide)s and poly(acrylate)s were synthesized by
      RAFT and ATRP methods. Similar to the synthesized poly(N-isopropylacrylamide) and
      poly(N-acryloylpyrrolidine), aqueous solutions of statistical acrylate copolymers
      bearing two different oligo(ethylene oxide) side chains showed a sharp clouding
      transition upon heating beyond characteristic temperatures. The temperature of
      the cloud point can be easily fine tuned by the copolymer composition. As for
      poly(N-isopropylacrylamide) and poly(N-acryloylpyrrolidine), the cloud-point
      temperatures of these statistical copolymers are rather insensitive to changes in
      the molar mass or the NaCl content of the solutions. Also, ternary triblock
      copolymers containing one permanently hydrophilic block and two different
      thermoresponsive blocks were synthesized, varying the block sequence
      systematically. Their aggregation in aqueous solution was followed by
      turbidimetry and dynamic light scattering. Depending on the heating process and
      the triblock sequence, micellar aggregates of 40 to 600 nm size were found. The
      thermally induced aggregation behavior depends sensitively on the block sequence
      but is also subject to major kinetic effects. For certain block sequences, a
      thermally induced two-step association is observed when heating beyond the first
      and second cloud points of the thermoresponsive blocks. However, the thermal
      transition temperatures of the block polymers can differ from the thermal
      transition temperatures of the individual homopolymers. This may be caused by end
      group effects but also by mutual interactions of the different blocks in
      solution, as physical mixtures of the homopolymers exhibit deviations from a
      purely additive thermal behavior.

PMID- 17190490
TI  - Light-responsive hydrophobic association of azobenzene-modified poly(acrylic
      acid) with neutral surfactants.
AB  - Photoresponsive association between azobenzene-modified poly(acrylic acid)s
      (AMPs) and the nonionic surfactants tetraethylene glycol monododecyl ether and
      octadecyl ether (C12E4 and C18E4) has been achieved in dilute aqueous solution.
      The binding was investigated by (i) spectrophotometry that probes the polarity
      close to the azobenzene chromophore, (ii) capillary electrophoresis to obtain the
      amount of C12E4 bound per polymer chain, and (iii) pressure-area curves of
      Langmuir films to obtain information on the adsorption of AMP at the water-C18E4
      interface. Increasing hydrophobicity of AMP (with increasing degree of
      modification with azobenzene side-groups) tightened the association with C12E4 in
      the dark. Exposure to UV light rapidly converted the azobenzene to their more
      polar cis isomer, which in turn weakened the association with surfactant. Almost
      complete photorelease of bound C12E4 was obtained with the optimal structure of
      AMP. Adsorption on large interfaces is much less sensitive to light. The possible
      origin of the photoresponse is analyzed in terms of AMP affinity for surfactant
      assemblies and azobenzene penetration in the hydrophobic core of micelles. We
      propose that the photoswing of polarity is amplified by the binding to small
      micelles because of the small number of anchors involved. A few azobenzene
      anchors afford tight binding in the dark, but also detach more easily than the
      whole AMP chain upon photoisomerization.

PMID- 17190491
TI  - Self-assembled networks highly responsive to hydrocarbons.
AB  - Rheological studies were performed with aqueous salt solutions of anionic
      surfactant potassium oleate and its mixtures with hydrophobically modified
      polyacrylamide. Semidilute solutions of the surfactant in the presence of salt
      (KCl) demonstrate viscoelastic properties due to the formation of a transient
      network of entangled wormlike micelles. These systems are highly responsive to
      hydrocarbons: the addition of n-heptane or n-dodecane reduces the viscosity of
      solutions by up to 4 to 5 orders of magnitude, thus inducing the transition of a
      gellike system to a fluid one. It is the transformation of cylindrical surfactant
      micelles into spherical ones upon absorption of hydrocarbon that disrupts the
      network. The addition of a small amount (0.5 wt %) of associating polymer leads
      to up to a 5000-fold increase in the zero-shear viscosity and enhances the
      susceptibility to hydrocarbons. SANS data show that independently of the presence
      of polymer the radius of wormlike micelles is roughly equal to the length of a
      surfactant molecule, whereas the radius of spheres formed upon the absorption of
      hydrocarbon is 2-2.5-fold higher. A possible structure of the spherical micelles
      is discussed.

PMID- 17190493
TI  - Formation of vesicles in block copolymer-fluorinated surfactant complexes.
AB  - Spherical micellar aggregates have been obtained in chloroform by mixing
      poly(styrene)-block-poly(4-vinylpyridine) (PS-b-P4VP) diblock copolymers with
      perfluorinated surfactants (FS) bearing a carboxylic acid head. These micellar
      aggregates are resulting from the self-assembly of the insoluble P4VP/fluorinated
      complexes into a core surrounded by the soluble PS coronal chains. Their
      characteristic features have been studied as a function of various parameters
      including the composition of the PS-b-P4VP copolymer, the tail length of the
      fluorinated surfactant, the 4VP/FS molar ratio, the number of carboxylic acid
      group (1 or 2) on the surfactant, the presence of the PS block and of the
      fluorine atoms on the surfactant. Dilution of these initial micellar aggregates
      triggers a morphological reorganization resulting in the formation of more stable
      vesicles. The extent of this morphological transition is related to the
      solubility of the P4VP/fluorinated complexes during the dilution process. This
      transition is complete for short P4VP/FS complexes, incomplete for long P4VP/FS
      complexes, and not observed whenever an alpha,omega-difunctional FS is used in
      P4VP/FS complexes, leading to a cross-linked core. Finally, the spheres-to
      vesicles transition has been advantageously used in order to encapsulate
      molecules, as demonstrated by confocal fluorescence microscopy.

PMID- 17190492
TI  - Quantification of amplified quenching for conjugated polymer microsphere systems.
AB  - A series of nonaggregating carboxylate-functionalized poly(phenylene ethynylene)s
      (PPEs) have been synthesized for immobilization via electrostatic adsorption onto
      Eu3+-polystyrene microspheres with a mean diameter of 0.2 microm. This system is
      shown to constitute a ratiometric system that measures fluorescence quenching
      with high fidelity. The fluorescence quenching properties of the polymer-coated
      particles in response to methyl viologen and a naphthyl-functionalized viologen
      have been investigated in aqueous solutions to study the influence of
      electrostatic and hydrophobic interactions with pentiptycene-incorporated as well
      as macrocycle-containing polymers.

PMID- 17190494
TI  - Heterostructured magnetic nanotubes.
AB  - Heterostructured magnetic tubes with submicrometer dimensions were assembled by
      the layer-by-layer deposition of polyelectrolytes and nanoparticles in the pores
      of track-etched polycarbonate membranes. Multilayers composed of poly(allylamine
      hydrochloride) and poly(styrene sulfonate) assembled at high pH (pH > 9.0) were
      first assembled into the pores of track-etched polycarbonate membranes, and then
      multilayers of magnetite (Fe3O4) nanoparticles and PAH were deposited.
      Transmission electron microscopy (TEM) confirmed the formation of multilayer
      nanotubes with an inner shell of magnetite nanoparticles. These tubes exhibited
      superparamagnetic characteristics at room temperature (300 K) as determined by a
      SQUID magnetometer. The surface of the magnetic nanotubes could be further
      functionalized by adsorbing poly(ethylene oxide)-b-poly(methacrylic acid) block
      copolymers. The separation and release behavior of low molecular weight anionic
      molecules (i.e., ibuprofen, rose bengal, and acid red 8) by/from the multilayer
      nanotubes were studied because these tubes could potentially be used as
      separation or targeted delivery vehicles. The magnetic tubes could be
      successfully used to separate (or remove) a high concentration of dye molecules
      (i.e., rose bengal) from solution by activating the nanotubes in acidic solution.
      The release of the anionic molecules in physiologically relevant buffer solution
      showed that whereas bulky molecules (e.g., rose bengal) release slowly, small
      molecules (i.e., ibuprofen) release rapidly from the multilayers. The combination
      of the template method and layer-by-layer deposition of polyelectrolytes and
      nanoparticles provides a versatile means to create functional nanotubes with
      heterostructures that can be used for separation as well as targeted delivery.

PMID- 17190495
TI  - In-situ AFM studies of the phase-transition behavior of single thermoresponsive
      hydrogel particles.
AB  - The volume phase transition (VPT) behavior of individual thermally responsive
      poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc) hydrogel
      microparticles was studied by in-situ dynamic mode atomic force microscopy (AFM)
      and force spectroscopy during heating and cooling cycles. Hydrogel samples were
      prepared by electrostatic immobilization of microparticles to amine-modified gold
      surfaces. The AFM studies of particle deswelling were performed by varying the
      force applied on the particles during imaging as a function of the geometry and
      material of the AFM probe. Aluminum-coated silicon cantilevers were found to
      influence substantially the behavior of the particles during the VPT, leading to
      a significant shape change. Low force impact magnetic excitation of the AFM probe
      (MAC mode) during dynamic mode measurements resulted in an undisturbed deswelling
      behavior enabling observation of the expected volume changes of the particles
      without significant tip-sample interaction. Hence, MAC-mode AFM was determined to
      be the most suitable technique for in-situ AFM studies on volume and shape
      changes at single hydrogel particles during VPT. Elasticity measurements
      performed at single particles at temperatures below and above the VPT revealed a
      15-fold increase in the Young's modulus after passing the VPT, indicating the
      transition from a soft, swollen network to a stiffer, deswollen state.

PMID- 17190497
TI  - Responsive hybrid self-assemblies in aqueous media.
AB  - Responsive copolymers have been prepared by grafting onto a poly(acrylamide-co
      sodium acrylate) backbone [PAM-co-PANa] poly(N-isopropylacrylamide) stickers
      [PNIPA] characterized by a lower critical solution temperature (LCST) in water.
      From adsorption isotherms and DSC studies performed on PNIPA/silica mixtures, it
      was shown that PNIPA chains irreversibly interact with silica particles and that
      at low coverage they partially lose their responsiveness with temperature. When
      PNIPA is grafted onto a PAM-co-PANa backbone, which has no specific attraction to
      silica surfaces (only electrostatic repulsions), their binding process remains
      very similar to the one analyzed with PNIPA chains alone. Above critical
      copolymer and silica concentrations (Cp congruent with 1 g/L and CSi congruent
      with 30 g/L), hybrid networks can be formed following the rules of percolation
      theory. The viscoelastic properties of these networks are controlled by the
      concentration of inorganic cross links and the fraction of PNIPA grafts
      participating in bridges between particles, the others being involved in
      inelastic loops or pendant chains. For all of the mixtures investigated, an
      optimum weight ratio of RSi/PNIPA = 10-15 was found for the viscoelastic
      properties, in agreement with the saturation of silica beads by the copolymer.
      Because of the responsive behavior of PNIPA in aqueous solutions, graft
      copolymers are able to self-assemble with temperature, giving rise to a sol/gel
      transition upon heating. In the presence of added silica, hybrid aggregates
      (silica/PNIPA) coexist at high temperature with organic ones (PNIPA/PNIPA) with
      synergistic or antagonistic effects on the elastic properties depending on the
      proportion of PNIPA grafts per silica particle.

PMID- 17190496
TI  - Preparation and characterization of polyion complex micelles with a novel
      thermosensitive poly(2-isopropyl-2-oxazoline) shell via the complexation of
      oppositely charged block ionomers.
AB  - Novel thermosensitive polyion complex (PIC) micelles were prepared in an aqueous
      medium based on the complexation of a pair of oppositely charged block ionomers,
      poly(2-isopropyl-2-oxazoline)-b-poly(amino acid)s (PiPrOx-b-PAA), containing
      thermosensitive PiPrOx segments. The controlled synthesis of PiPrOx-b-PAA was
      achieved via the ring-opening anionic polymerization of N-carboxyanhydrides (NCA)
      of either eta-benzyloxycarbonyl-l-lysine (Lys(Z)-NCA) or beta-benzyl-l-aspartate
      (BLA-NCA) with omega-amino-functionalized PiPrOx macroinitiators and the
      subsequent deprotection reaction under acidic or basic conditions. Gel permeation
      chromatography (GPC) and 1H NMR spectroscopy revealed that the syntheses of two
      block ionomers, poly(2-isopropyl-2-oxazoline)-b-poly(l-lysine) [PiPrOx-P(Lys)]
      and poly(2-isopropyl-2-oxazoline)-b-poly(aspartic acid) [PiPrOx-P(Asp)],
      proceeded almost quantitatively to give samples with a narrow molecular weight
      distribution (Mw/Mn </= 1.2). The mixing of these two oppositely charged block
      ionomers in an aqueous medium led to the spontaneous formation of PIC micelles,
      which was confirmed by dynamic light scattering (DLS) and transmission electron
      microscopy (TEM). The PIC micelles were spherical particles with a narrow
      distribution in the range of the measured concentration (0.125-1 mg/mL) and were
      stable without any secondary aggregates. Furthermore, the PIC micelles had a
      constant cloud-point temperature (Tcp) of approximately 32 degrees C under
      physiological conditions regardless of the total concentration, suggesting that
      the concentration factor is almost negligible with respect to the Tcp of the
      micelles presumably because of the increased local concentration of the PiPrOx
      segments in the shell layer. These PIC micelles have a promising application as a
      size-regulated smart nanocontainer loading charged compounds as well as bearing a
      thermosensitive outer shell that is useful for physical affinity control.

PMID- 17190498
TI  - Thermoresponsive coatings strongly adhering to (semi)conducting surfaces.
AB  - Thermoresponsive brushes have been efficiently grafted onto (semi)conductive
      surfaces by a two-step process. In the first step, poly(N-succinimidyl acrylate)
      chains have been chemisorbed onto silicon or stainless steel by the
      electrografting method. Then, these modified electrodes were immersed in
      isopropylamine in order to transform the grafted chains to the thermoresponsive
      poly(N-isopropyl acrylamide). The thermal response of these brushes has been
      shown by AFM. This straightforward grafting process is quite attractive for
      surface modification in confined media and is thus promising for microfludics
      application.

PMID- 17190499
TI  - End-grafted low-molecular-weight PNIPAM does not collapse above the LCST.
AB  - The interfacial properties of end-grafted temperature-responsive poly(N
      isopropylacryamide) (PNIPAM) were quantified by direct force measurements both
      above and below the lower critical solution temperature (LCST) of 32 degrees C.
      The forces were measured between identical, opposing PNIPAM films and between a
      PNIPAM film and a lipid membrane. At the grafting densities and molecular weights
      investigated, the polymer extension did not change significantly above the LCST,
      and the polymers did not adhere. Below the LCST, the force-distance profiles
      suggest a vertical phase separation, which results in a diluter outer layer and a
      dense surface proximal layer. At large separations, the force profiles agree
      qualitatively with simple polymer theory but deviate at small separations.
      Importantly, at these low grafting densities and molecular weights, the end
      grafted PNIPAM does not collapse above the LCST. This finding has direct
      implications for triggering liposomal drug release with end-grafted PNIPAM, but
      it increases the temperature range where these short PNIPAM chains function as
      steric stabilizers.

PMID- 17190501
TI  - Amphoteric surface hydrogels derived from hydrogen-bonded multilayers: reversible
      loading of dyes and macromolecules.
AB  - We used hydrogen-bonded multilayers of poly(N-vinylpyrrolidone) (PVPON) and
      poly(methacrylic acid) (PMAA) as precursors for producing surface-bound hydrogels
      and studied their pH-dependent swelling and protein uptake behavior using in situ
      attenuated total reflection Fourier transform infrared spectroscopy and in situ
      ellipsometry. The hydrogels were produced by selective chemical cross-linking
      between PMAA units using carbodiimide chemistry and ethylenediamine (EDA) as a
      cross-linking reagent, followed by complete removal of PVPON from the film
      obtained by exposing the film to pH 7.5. As shown by in situ ellipsometry,
      hydrogels exhibit distinctive polyampholytic swelling as a function of pH, with
      minimum swelling at pH 4.2-5.7, and increased film thickness at both lower and
      higher pH values. Film swelling at lower pH values occurs as a result of the
      presence of amino groups within the hydrogels, which originate from the one-end
      attachment of the EDA cross-linker to PMAA chains. The pH-switching of hydrogel
      swelling was fast and reversible. The degree of hydrogel swelling could be also
      controlled by varying the time allowed for cross-linking. The produced hydrogels
      were able to absorb large amounts of dyes and proteins of opposite charge
      reversibly, in response to pH variations. Finally, we demonstrate that proteins
      included within the hydrogel can easily be replaced with linear polycations.
      These surface hydrogels hold promise for bioseparation and controlled delivery
      applications.

PMID- 17190500
TI  - Thermoresponsive transport through ordered mesoporous silica/PNIPAAm copolymer
      membranes and microspheres.
AB  - Thermosensitive inorganic-organic hybrid polymers and gels can be used for
      controlled molecular transport in a variety of applications that require robust,
      mechanically stable materials. Silica and poly(N-isopropylacrylamide) (PNIPAAm)
      precursors were copolymerized in the presence of surfactant supramolecular
      assemblies to form hybrid gels with ordered nanostructure. This method was less
      complicated and results in enhanced reversible transport properties compared to
      previous approaches noted herein. In this study, the thermoresponsive polymer,
      PNIPAAm, was incorporated into polymerizing silica networks using the coupling
      agent 3-methacryloxypropyltrimethoxysilane. The hydration transition of PNIPAAm
      associated with its lower critical solution temperature (LCST) in aqueous
      solution was retained in the hydrated silica matrices and was used to control the
      permeability of membranes and molecular release behavior of particles. This
      report presents new methods for formation of hybrid silica/PNIPAAm membranes and
      particles, characterization of these materials, and documentation of reversible
      molecular transport properties of these new hybrid materials.

PMID- 17190502
TI  - Stimuli-responsive polyelectrolyte polymer brushes prepared via atom-transfer
      radical polymerization.
AB  - We present an account of our research into polyelectrolyte polymer brushes that
      are capable of acting as stimuli-responsive films. We first detail the synthesis
      of poly(acrylic acid) polymer brushes using ATRP in a "grafting from" strategy.
      Significantly, we employed a chemical-free deprotection step that should leave
      the anchoring ester groups intact. We have demonstrated how these polymer
      assemblies respond to stimuli such as pH and electrolyte concentration. We have
      used poly(acrylic acid) polymer brushes for the synthesis of metallic
      nanoparticles and review this work. We have used XPS, ATR-FTIR, and AFM
      spectroscopy to show the presence of silver and palladium nanoparticles within
      polymer brushes. Finally, we report the synthesis of AB diblock polyampholyte
      polymer brushes that represent an extension of polyelectrolyte polymer brushes.

PMID- 17190503
TI  - pH-controlled reversible assembly of peptide-functionalized gold nanoparticles.
AB  - The assembly/disassembly process of carboxylated peptide-functionalized gold
      nanoparticles (peptide-GNPs) was studied within the pH interval of 2.5 to 10. The
      assembly process was not well controlled at pH 2.5, leading to the formation of
      3D structures of GNPs, whereas at pH 4 we observed controlled assembly with the
      formation of only a network of 1D chains. In the pH range of 2.5 to 4, the
      assembly proceeded with the formation of a combination of two extremes (i.e.,
      having both 1D and 2D nanostructures). The assembly process was reversed on
      changing the pH of the medium to 10. The assembly/disassembly process was
      monitored using UV-vis spectroscopy and finally confirmed by TEM analysis. This
      assembly resulted from the intermolecular H-bonding between two carboxylic acid
      groups of peptides bound to the two adjacent GNPs and were confirmed by FTIR
      spectroscopy.

PMID- 17190504
TI  - Microgels loaded with gold nanorods: photothermally triggered volume transitions
      under physiological conditions.
AB  - Photothermally driven volume transitions in polymer microgels have promising
      applications for site-specific drug delivery and photodynamic therapy. We studied
      the temperature-induced volume phase transitions for a series of thermoresponsive
      microgels of various compositions to find a system with a sharp transition in the
      physiologically relevant range spanning 38-41 degrees C in 0.01 M phosphate
      buffered saline solution (pH = 7.4). We found that the poly(N-isopropylacrylamide
      maleic acid) microgels showed an 8-fold decrease in size under the aforementioned
      conditions. These microgels were loaded with gold nanorods designed to absorb in
      the near-IR spectral range. Following irradiation at lambda = 809 nm, the
      microgels underwent a large, reversible, photothermally triggered change in
      volume. We believe that this microgel system is a promising candidate for
      photothermally controlled drug release.

PMID- 17190505
TI  - Morphology-tunable and photoresponsive properties in a self-assembled two
      component gel system.
AB  - Photoresponsive C3-symmetrical trisurea self-assembling building blocks
      containing three azobenzene groups (LC10 and LC4) at the rim were designed and
      synthesized. By introducing a trisamide gelator (G18), which can self-aggregate
      through hydrogen bonds of acylamino moieties to form a fibrous network, the
      mixture of LC10 (or LC4) and G18 forms an organogel with coral-like
      supramolecular structure from 1,4-dioxane. The cooperation of hydrogen bonding
      and the hydrophobic diversity between these components are the main contributions
      to the specific superstructure. The two-component gel exhibits reversible
      photoisomerization from trans to cis transition without breakage of the gel
      state.

PMID- 17190506
TI  - Water makes it hydrophobic: contraphilic wetting for polyurethanes with soft
      blocks having semifluorinated and 5,5-dimethylhydantoin side chains.
AB  - A series of polyurethanes with novel copolymer soft blocks display a new surface
      phenomenon, contraphilic wetting, in which the dry surface is hydrophilic and the
      wetted surface is hydrophobic. A precursor polymer was prepared with copolymer
      soft blocks containing semifluorinated (trifluoroethoxy, 3FOx, or
      pentafluoropropoxy, 5FOx) and bromomethyl functional pendant groups with 2:1,
      1:1, and 1:2 semifluorinated/bromomethyl ratios. The hard block consists of
      isophorone diisocyanate (IPDI) and 1,4-butanediol (BD). 5,5-Dimethylhydantoin was
      introduced by the substitution of Br via reaction-on-polymer. The composition,
      structure, and percent of 5,5-dimethylhydantoin substitution for both the
      precursor and the 5,5-dimethylhydantoin-substituted polyurethanes were analyzed
      by 1H NMR. The difference between the advancing contact angle on the wetted
      surface and that on the dry surface (deltaC) is highest (38 degrees ) for the
      polyurethane with the highest ratio of semifluorinated/hydantoin soft block side
      chains. A model is proposed according to which contraphilic wetting is driven
      enthalpically by hydrogen bonding. For the dry surface, hydrogen bonding of 5,5
      dimethylhydantoin amide carbonyl groups to methylene hydrogens of semifluorinated
      groups disrupts the normal surface concentration of semifluorinated groups,
      whereas the geometric arrangement of hydantoin N-H results in availability for
      hydrogen bonding with water. Upon exposure to water, amide groups switch from
      hydrogen bonding to -CH2CF2CF3 to stronger hydrogen bonding with water. As a
      result, semifluorinated groups are "released", and the surface becomes
      hydrophobic. Drying the coating (50 degrees C) reversibly restores hydrophilic
      character. Coatings stored at ambient temperature and humidity have deltaC values
      intermediate between dry and wet states.

PMID- 17190507
TI  - Botryoidal assembly of cholesteryl-pullulan/poly(N-isopropylacrylamide) nanogels.
AB  - Hybrid nanogels consisting of cholesteryl-modified pullulan (CHP) and poly(N
      isopropylacrylamide) (PNIPAM) were synthesized by graft free-radical
      copolymerization of N-isopropylacrylamide (NIPAM) onto methacryloyl-substituted
      CHP nanogels (CHPMA) in water at 50 degrees C in the presence of a water-soluble
      free radical initiator. Depending on the initial NIPAM/CHPMA ratio, CHP-PNIPAM
      (CN) nanogels containing 30.8-84.8 wt % PNIPAM were obtained in the form of self
      assembled nanoparticles with a hydrodynamic radius (Rh) of 69.0-116.0 nm in water
      kept at 20 degrees C. Hybrid nanogels of sufficiently high NIPAM content, such as
      the sample CN90, which contains 79.6 wt % NIPAM, exhibited a two-step response to
      changes in solution (3 mg/mL) temperature: a decrease in Rh from 93 to 57 nm as
      the temperature increased from 20 to 35 degrees C, followed by a sharp increase
      in Rh from 57 nm to 90 nm at 55 degrees C. Both steps in this temperature
      response were reversible. The multistep response to temperature of the CN
      nanogels was attributed to the morphology of the nanogels, which are seen as
      consisting of grape-like (botryoidal) clusters of associated native nanogels held
      together via cholesteryl cross-linking points and held together by the grafted
      PNIPAM chains.

PMID- 17190508
TI  - Photo-, thermally, and pH-responsive microgels.
AB  - Microgels with photo-, thermally, and pH-responsive properties in aqueous
      suspension have been synthesized and characterized using dynamic light scattering
      and UV-visible spectroscopy. The new route involved first preparing poly(N
      isopropylacrylamide) (PNIPAM)-allylamine copolymer microgels and a spiropyran
      photochrome (SP) bearing a carboxylic acid group. Then the functionalized
      spiropyran was coupled to the microgel via an amide bond. The dark-equilibrated
      gel particles feature spiropyran molecules in the polar, merocyanine form. After
      irradiation of visible light, the particle size becomes smaller because
      spiropyran changes to the relatively nonpolar, closed spiro form. The PNIPAM-SP
      microgels undergo a volume phase transition in water from a swollen state to a
      collapsed state with increasing temperature under all light conditions. However,
      the transition temperature range of the PNIPAM-SP is much broader than that for
      the PNIPAM without SP. The PNIPAM-SP microgels are monodisperse and self-assemble
      into a crystalline lattice while in suspension. The UV-visible spectra of an
      aqueous suspension of PNIPAM-SP microgel in the dark-adapted, merocyanine form
      showed both an absorption peak around 512 nm due to the merocyanine (giving a
      reddish color to the suspension) and two sharp peaks from Bragg diffraction of
      colloidal crystallites. Upon visible irradiation, the 512-nm band bleached
      significantly due to spiropyran photoisomerization. The spiropyran
      photoisomerization and accompanying color changes of the suspension were
      reversible upon alternating dark, UV, and visible light irradiation. Due to the
      residues of amine groups, the swelling capability of PNIPAM-SP microgels reduces
      as the pH value is changed from 7 to 10.

PMID- 17190509
TI  - Layer-by-layer assembly of pH-responsive, compositionally controlled
      (co)polyelectrolytes synthesized via RAFT.
AB  - Homo- and block copolyelectrolytes that have well-defined structures and are
      responsive to pH were synthesized via reversible addition-fragmentation chain
      transfer (RAFT) polymerization and employed to produce layer-by-layer (LBL)
      films. Acrylamido monomers with carboxylate, sulfonate, and amine functionality
      were utilized to provide both strong and weak homopolyelectrolytes and mixed
      strong/weak copolyelectrolyte systems. Multilayer films were prepared under
      specified conditions of pH and ionic strength and analyzed via atomic force
      microscopy and ellipsometry to study the effects of changes in the local
      molecular environment on film morphologies. The pH responsiveness and integrity
      of the multilayer assemblies were investigated by exposing films to solutions of
      varying pH in a fluid cell and performing in situ AFM analysis. The multilayer
      dimensions, morphology, and integrity were found to depend on the molecular
      architecture of the polyelectrolytes, with changes in segmental type and
      repeating unit distribution producing dramatic differences in film
      characteristics. These results suggest the possibility of producing LBL
      assemblies of precisely controlled dimensions and properties by specifically
      tailoring copolymer structure. To our knowledge, this is the first report of LBL
      assembly of RAFT-synthesized homo- and copolyelectrolyte multilayer complexes.

PMID- 17190510
TI  - Synthesis and in situ atomic force microscopy characterization of temperature
      responsive hydrogels based on poly(2-(dimethylamino)ethyl methacrylate) prepared
      by atom transfer radical polymerization.
AB  - Well-defined copolymers of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and
      benzophenone methacrylate (BPMA) with different compositions were synthesized via
      atom transfer radical polymerization. The molecular weights of these copolymers
      were Mn approximately 30 000 g/mol, while the BPMA content varied from 2.5 to 10
      mol %. The copolymers with a low content of BPMA (2.5 and 5 mol %) exhibited a
      sharp thermal transition at 33-36 degrees C in aqueous solution. A hydrogel was
      immobilized and patterned on a silicon wafer via UV treatment of the spin-coated
      polymer layer using a photomask technique. The thermoresponsive behavior of the
      patterned polymer gel was quantitatively investigated by variable temperature in
      situ contact mode atomic force microscopy, which revealed the presence of two
      lower critical solution temperature regions. One region was between 25 and 30
      degrees C, corresponding to the topmost layer of the hydrogel film, and the other
      region, around 40 degrees C, corresponded to the bulk of the hydrogel. Concurrent
      lateral force microscopy measurements revealed that, just above the transition
      temperature, the bulk region exhibited enhanced friction.

PMID- 17190511
TI  - Switchable friction of stimulus-responsive hydrogels.
AB  - Poly(N-isopropylacrylamide) (pNIPAAm) gels are stimulus-responsive hydrogels that
      exhibit large reversible changes in their volume and surface physicochemical
      properties near the lower critical solution temperature (LCST) in response to
      external stimuli, such as a change in temperature or solvent composition. Here we
      report how different phase states, induced isothermally by changes in the solvent
      composition, affect the tribological properties of pNIPAAm hydrogels. Our
      measurements indicate that gels in a collapsed conformation (above the LCST)
      exhibit significantly more friction than swollen gels (below the LCST) at low
      shear rates. These differences arise from changes in the surface roughness,
      adhesive interactions, and chain entanglements of the gel surfaces associated
      with the phase transition. Importantly, we show that the changes in friction,
      triggered by an external stimulus, are reversible. These reversible and possibly
      tunable changes in friction may have a significant impact on the design of
      coatings for biosensors and for actuation devices based on stimulus-responsive
      hydrogels.

PMID- 17190512
TI  - Characterization of superlighting polymer-DNA aggregates: a fluorescence and
      light scattering study.
AB  - The massive amplification of fluorescence signal observed upon hybridization of
      as few as five DNA molecules into self-assembled structures formed between a
      cationic polymer and DNA oligonucleotides is investigated. These superlighting
      polymer-DNA aggregates were studied by fluorescence spectroscopy, static and
      dynamic light scattering, and zeta potential measurements in order to
      characterize the aggregation behavior and to understand the processes involved
      during DNA detection. Multi-angle laser light scattering was also used to obtain
      the weight-average aggregate mass (AM), the aggregation number (Nagg), the radius
      of gyration (Rg), and the dissymmetry ratio (z). These results have been used,
      together with TEM imaging, to propose a suitable physical model for the
      aggregates.

PMID- 17190513
TI  - Adaptive nanomechanical response of stratified polymer brush structures.
AB  - We have fabricated a stratified polymer surface film with tunable thickness
      (within 17-34 nm) through facile, room-temperature, UV-initiated polymerization
      with a temperature-sensitive pNIPAAM layer confined beneath a hydrophobic layer.
      AFM morphology and ellipsometric measurements were measured at each grafting
      step, along with XPS measurements of the overall layer to verify layer growth.
      The strong characteristic LCST behavior of pNIPAAM was observed in water, with a
      100% change in thickness above and below this transition. The AFM nanomechanical
      results demonstrate vertical gradients of the elastic response tunable to a
      desired state by the external temperature. These temperature-sensitive, adaptive
      polymer structures with the pNIPAAM layer "hidden" beneath the rubbery,
      hydrophobic PBA topmost layer represent an interesting example of nanoengineering
      surfaces with properties such as adhesion, elastic modulus, and multi-level
      structural reorganization responsive to fluidic and temperature variations that
      can be important for biological purposes such as implant coatings, cell-surface
      mimicry, and drug delivery vehicles.

PMID- 17190514
TI  - Color-tunable fluorescent organogels: columnar self-assembly of pyrene-containing
      oligo(glutamic acid)s.
AB  - New fluorescent gelators containing pyrene moieties and dendritic oligopeptides
      have been developed. These molecules self-assemble into 1D helical columnar
      structures that lead to the formation of 3D fibrous random networks. The
      resulting gel materials show monomer emission of pyrenes because the hydrogen
      bonded array of the oligopeptide moieties greatly suppresses the formation of
      pyrene excimers. In contrast, in the sol states green excimer emission of the
      pyrenes is observed because of the dissociation of intermolecular hydrogen bonds.
      This is the first example of the reverse-mode color switching of fluorescence for
      supramolecular pyrene assemblies.

PMID- 17190515
TI  - Memory of surface patterns in mixed polymer brushes: simulation and experiment.
AB  - The correlation between the morphology of mixed polymer brushes and fluctuations
      of the grafting points is investigated by single-chain-in-mean-field simulations
      and experiments. The local topography of two types of mixed polystyrene
      polymethylmethacrylate (PS-PMMA) brushes that differ in their modes of attachment
      has been studied during repeated microphase separation into laterally structured
      and homogeneous morphologies upon changing solvents. In the first type of brush
      (conventional), each of the surface-attached initiator groups starts the growth
      of either a PS or a PMMA chain in a random fashion. In the second case (Y-shaped
      mixed brushes), two chains of different types are attached to the same anchor
      group on the substrate. Whereas in the first case statistical fluctuations of the
      chemical composition occur on a local scale, such composition fluctuations are
      strongly suppressed in the latter case. The microphase-separated morphology is
      similar in both cases, but Y-shaped brushes exhibit a significantly weaker domain
      memory than do conventional PS-PMMA mixed brushes. The results of the experiment
      are compared with simulations, and a simple phenomenological argument and
      qualitative agreement are found. The observations demonstrate that small
      fluctuations in the grafting points are amplified by the microphase separation
      and nucleate the location of the domains in the mixed brush.

PMID- 17190516
TI  - Reversible vesicle restraint in response to spatiotemporally controlled
      electrical signals: a bridge between electrical and chemical signaling modes.
AB  - Microelectronic devices employ electrons for signaling whereas the nervous system
      signals using ions and chemicals. Bridging these signaling differences would
      benefit applications that range from biosensing to neuroprosthetics. Here, we
      report the use of localized electrical signals to perform an operation common to
      chemical signaling in the nervous system. Specifically, we employ electrical
      signals to restrain vesicles reversibly. We perform this operation using the
      stimuli-responsive aminopolysaccharide chitosan that is able to electrodeposit
      onto cathode surfaces in response to localized electrical stimuli. We show that
      surfactant-vesicles and liposomes can be co-deposited with chitosan and are
      entrapped (i.e., restrained) within the deposited film's matrix. Vesicle co
      deposition could be controlled spatially and temporally using microfabricated
      wafers with independent electrode addresses. Finally, we show that vesicles
      restrained within the deposited chitosan matrix can be mobilized under mildly
      acidic conditions (pH <6.5) that resolubilize chitosan. Potentially, the ability
      to restrain and mobilize chemical signals that are segregated within vesicles may
      allow microfluidic systems to access the rich diversity offered by chemical
      signaling.

PMID- 17190517
TI  - Electrochemical desorption of n-alkylthiol SAMs on polycrystalline gold: studies
      using a ferrocenylalkylthiol probe.
AB  - The reductive voltammetric desorption of n-alkylthiol self-assembled monolayers
      (SAMs) was studied using ferrocenyldodecanethiol (FcC12SH) as a probe. A short
      (10 s) incubation in a 2 mM FcC12SH solution labels the pre-existing defect sites
      present in a tetradecanethiol (C14S-Au) SAM. Additional defects in a C14S-Au SAM
      are then created by voltammetric cycling to reductive potentials. The effects of
      changing the desorption potential and the hold time at the desorption potential
      were investigated by monitoring the change in the two characteristic FcC12S-Au
      peaks. These two peaks are associated with FcC12S-Au filling individual single
      site defects (peak I at 260 mV) and pinhole defects (peak II at 380 mV). The
      reductive desorption potential applied to a binary (FcC12S-/C14S-Au) SAM results
      in a partial desorption and a potential "remixing" of the phase-separated state.

PMID- 17190518
TI  - Switching the electrochemical impedance of low-density self-assembled monolayers.
AB  - Because the active remodeling of biointerfaces is a paramount feature of nature,
      it is very likely that future, advanced biomaterials will be required to mimic at
      least certain aspects of the dynamic properties of natural interfaces. This need
      has fueled a quest for model surfaces that can undergo reversible switching upon
      application of external stimuli. Herein, we report the synthesis and
      characterization of a model system for studying reversibly switching surfaces
      based on low-density monolayers of mercaptohexadecanoic acid and
      mercaptoundecanoic acid. These monolayers were assembled on both gold and silver
      electrodes. When conducting electrochemical impedance spectroscopy under
      physiological conditions, these monolayers exhibit significant changes in their
      electrochemical barrier properties upon application of electrical DC potentials
      below +400 mV with respect to a standard calomel electrode. We further found the
      impedance switching to be reversible under physiological conditions. Moreover,
      the impedance can be fine-tuned by changing the magnitude of the applied
      electrical potential. Before and during impedance switching at pH 7.4 in aqueous
      buffer solutions, the low-density monolayers showed good stability according to
      grazing angle infrared spectroscopy data. We anticipate low-density monolayers to
      be potentially useful model surfaces when designing active biointerfaces for cell
      based studies or rechargeable biosensors.

PMID- 17190519
TI  - Temperature-controlled flow switching in nanocapillary array membranes mediated
      by poly(N-isopropylacrylamide) polymer brushes grafted by atom transfer radical
      polymerization.
AB  - We report actively controlled transport that is thermally switchable and size
      selective in a nanocapillary array membrane (NCAM) prepared by grafting poly(N
      isopropylacrylamide) (PNIPAAm) brushes onto the exterior surface of a Au-coated
      polycarbonate track-etched membrane. A smooth Au layer on the membrane surface,
      which is key to obtaining a uniform polymer film, was prepared by thermal
      evaporation of approximately 50 nm Au on both exterior surfaces. After
      evaporation, the inner diameter of the pore is reduced slightly, but the NCAM
      retains a narrow pore size distribution. PNIPPAm brushes with 10-30 nm (dry film)
      thickness were grafted onto the Au surface through surface-initiated atom
      transfer radical polymerization (ATRP) using a disulfide initiator,
      (BrC(CH3)2COO(CH2)11S)2. Molecular transport through the PNIPAAm polymer brush
      modified NCAMs was investigated by real-time fluorescence measurements using
      fluorescein isothiocyanate (FITC)-labeled dextrans ranging from 4.4 to 282 kDa in
      membranes with variable initial pore diameters (80, 100, and 200 nm) and
      different PNIPAAm thicknesses. Manipulating the temperature of the NCAM through
      the PNIPAAm lower critical solution temperature (LCST) causes large, size
      dependent changes in the transport rates. Over specific ranges of probe size,
      transport is completely blocked below the LCST but strongly allowed above the
      LCST. The combination of the highly uniform PNIPAAm brush and the monodisperse
      pore size distribution is critical in producing highly reproducible switching
      behavior. Furthermore, the reversible nature of the switching raises the
      possibility of using them as actively controlled filtration devices.

PMID- 17190520
TI  - Nonvolatile polymer memory device based on bistable electrical switching in a
      thin film of poly(N-vinylcarbazole) with covalently bonded C60.
AB  - A functional polymer (PVK-C60), containing carbazole moieties (electron donors)
      and fullerene moieties (electron-acceptors) in a molar ratio of about 100:1, was
      synthesized via covalent tethering of C60 to poly(N-vinylcarbazole) (PVK). The
      molecular structure and composition of PVK-C60 were characterized by FTIR, Raman,
      and UV-vis absorption spectroscopy, gel permeation chromatography (GPC), X-ray
      photoelectron spectroscopy (XPS), and cyclic voltammetry (CyV). The C60-modified
      PVK exhibited an enhanced glass-transition temperature (Tg = 226 degrees C) and
      good solubility in organic solvents such as toluene, tetrahydrofuran, chloroform,
      and N,N-dimethylformamide (DMF). It could be cast into transparent films from
      solutions. For a thin film of PVK-C60 sandwiched between an indium tin oxide
      (ITO) electrode and an Al electrode (ITO/PVK-C60/Al), the device behaved as
      nonvolatile flash (rewritable) memory with accessible electronic states that
      could be written, read, and erased. The polymer memory exhibited an ON/OFF
      current ratio of more than 105 and write/erase voltages around -2.8 V/+3.0 V.
      Both the ON and OFF states were stable under a constant voltage stress of -1 V
      for 12 h and survived up to 108 read cycles at -1 V under ambient conditions.

PMID- 17190521
TI  - Formation of bragg gratings with large angular multiplicity by means of the
      photoinduced reorientation of azobenzene copolymers.
AB  - Optically transparent thick films of methacrylate copolymer containing donor
      acceptor-type azobenzene and cyanobiphenyl moieties were prepared, and their
      optical properties were explored in terms of a photoinduced change in molecular
      alignment and the formation of Bragg gratings with angular and polarization
      multiplicity. Azobenzene moieties substituted with ethoxy, cyano, and nitro
      groups were employed, and their photoresponsive behavior was investigated. It was
      found by polarized UV-vis spectroscopy that the alignment of azobenzene moieties
      in the films was random in the initial state but became perpendicular to the
      direction of polarization of the writing beam after irradiation with a linearly
      polarized beam from an Ar+ laser at 514 nm. The film containing the
      cyanoazobenzene moieties showed the fastest formation of optical anisotropy due
      to an efficient change in molecular alignment. When two linearly polarized beams
      from the Ar+ laser were allowed to interfere in the films with a thickness of 200
      microm, the diffraction beam was observed immediately and reached 97% upon
      photoirradiation at 200 mW/cm2 for 5 min. It was clearly observed that the
      response time became shorter with an increase in the light intensity of the
      writing beams, maintaining the high diffraction efficiency. Furthermore, it was
      clearly seen that the diffraction efficiency strongly depended on the direction
      of polarization of the reading beam. Holographic multiple data storage in a film
      was demonstrated, and 55 holograms with angular multiplicity were recorded
      successfully. In addition, multiple data storage using the polarization and angle
      selectivity simultaneously was first demonstrated.

PMID- 17190522
TI  - Controllable water permeation on a poly(N-isopropylacrylamide)-modified
      nanostructured copper mesh film.
AB  - Water permeation is important for various applications in industry, agriculture,
      and daily life. However, most research mainly focuses on the static wettability
      on different surfaces, and the dynamic properties of the micro- and nanostructure
      enhanced responsive wettability is lacking. And the relevant application research
      is rare, which still remains a challenge. Herein we report the temperature
      controllable water permeation on a poly(N-isopropylacrylamide)-modified
      nanostructured copper mesh film. At low temperatures (below 25 degrees C), the
      film shows good water permeability because of the highly hydrophilic nature, and
      as a result, the water can easily penetrate through the film. At high
      temperatures (above 40 degrees C), it is impermeable to water because of the
      superhydrophobicity and the large negative capillary effect induced by the micro-
      and nanostructures. The excellent controllability of water permeation on this
      film may be convenient for use in many processes including filtration, water/oil
      separation, and so on. A detailed investigation indicates that the special
      nanostructures and the appropriate size of the microscale mesh pores not only
      influence the static contact angles of the mesh film, but also, more importantly,
      greatly improve the dynamic properties of wettability at different temperatures
      simultaneously, which plays a crucial role in the excellent controllability over
      water permeation on this film. This work may also provide interesting insight
      into the design of novel functional devices that are relevant to surface
      wettability.

PMID- 17190523
TI  - Bragg-type polarization gratings formed in thick polymer films containing
      azobenzene and tolane moieties.
AB  - Holographic gratings were formed in thick polymer films containing azobenzene and
      diphenylacetylene (tolane) moieties in the Bragg regime. Amorphous polymers
      containing various contents of the azobenzene moiety with photosensitivity and
      the tolane moiety with large birefringence in the side chain were synthesized,
      and optically transparent thick polymer films were prepared. The films were
      irradiated with a linearly polarized beam from an Ar+ laser (488 nm), and the
      transmittance of a He-Ne laser beam (633 nm) through a pair of crossed
      polarizers, with the film between them, was measured to estimate a photoinduced
      birefringence (deltan). The value of deltan increased with an increase in the
      tolane moiety content in the polymer films. When two linearly polarized beams at
      488 nm were interfered in the film, a diffraction beam was observed, and the
      maximum diffraction efficiency (eta) increased with the tolane moiety content. In
      the film containing 70 mol% of the tolane moiety, the highest eta of 99% was
      achieved, and angular selectivity due to Bragg diffraction was clearly observed.
      We consider the cooperative molecular motion of the tolane moieties to be induced
      by the photoinduced change in alignment of the azobenzene moieties even if the
      polymers show no liquid-crystalline phase. When two orthogonal circularly
      polarized beams were allowed to interfere in the film, a Bragg-type polarization
      grating was formed. It was found that the value of eta reached 90% within 920 ms.

PMID- 17190524
TI  - Microcantilever sensing and actuation with end-grafted stimulus-responsive
      elastin-like polypeptides.
AB  - Stimulus-responsive elastin-like polypeptides (ELPs) grafted onto surfaces are of
      significant technical interest because they can be exploited for force
      generation, in sensing applications, or as molecular switches with tunable
      properties. Changes in the conformational state of grafted ELPs, induced by a
      phase transition or changes in osmotic pressure, lead to significant changes in
      the surface stress in the ELP graft layer and translate into detectable changes
      in microcantilever deflection. In this study, we investigate the conformational
      mechanics of ELPs in response to changes in solution pH and ionic strength using
      atomic force microscopy (AFM) microcantilever deflection and quartz crystal
      microbalance (QCM) measurements. We show that the use of genetically encoded,
      surface-grafted ELPs is exciting for cantilever actuation and sensing because
      commonly available microfabricated cantilever springs offer a simple and
      nonintrusive way to detect changes in solvent type, temperature, and pH,
      promising great potential for sensing applications in microfluidic devices.

PMID- 17190525
TI  - Mitochondrial dysfunction as the molecular basis of bipolar disorder: therapeutic
      implications.
AB  - Multiple lines of evidence, such as impaired energy metabolism in the brain
      detected by magnetic resonance spectroscopy, a possible role of maternal
      inheritance, co-morbidity with mitochondrial diseases, the effects of mood
      stabilisers on mitochondria, increased mitochondrial DNA (mtDNA) deletion in the
      brain, and association with mtDNA mutations/polymorphisms or nuclear-encoded
      mitochondrial genes, suggest that mitochondrial dysfunction is an important
      component of bipolar disorder. Global reduction of mitochondria-related gene
      expression in the postmortem brains of patients with bipolar disorder may also be
      an indicator, but such findings are affected by sample pH and thus need to be
      interpreted with caution. A recently developed animal model carrying mtDNA
      deletion in neurons suggested that accumulation of mtDNA deletions causes bipolar
      disorder-like phenotypes. The next step in the study of mitochondrial dysfunction
      in bipolar disorder should be clarification of how mitochondrial dysfunction, a
      nonspecific risk factor, can cause specific symptoms of bipolar disorder. Two
      hypothetical mechanisms are mtDNA neuroplasticity and nonvisual photoreception
      impairment. Further study of mitochondrial dysfunction in bipolar disorder is
      expected to be useful for the development of new mood stabilisers.

PMID- 17190528
TI  - Pharmacological management of attention-deficit hyperactivity disorder in
      adolescents: special considerations.
AB  - Approximately one-half of children medicated for attention-deficit hyperactivity
      disorder (ADHD) will continue to experience sufficient impairment during
      adolescence to warrant the continuation of their treatment; a smaller number of
      people with ADHD may require treatment for the first time during adolescence. The
      academic and social demands of adolescence can exaggerate the impairment caused
      by attentional problems, as adolescents, more so than children, have activities
      in the afternoon and evening that will tax their attentional abilities. Stimulant
      and nonstimulant medications are likely to be as effective for adolescent
      patients as they are for younger children, provided treatment adherence is
      satisfactory. Long-acting medications are preferred over immediate-release
      compounds as they provide better coverage of symptoms throughout the day.
      Patterns of comorbidity with ADHD change from childhood to adolescence and may
      require a shift in treatment strategy. The choice of time to discontinue
      treatment should be a decision shared by the clinician and the patient. A
      negotiated trial of time off treatment followed by a review of the patient's
      symptoms can avert premature discontinuation of treatment.

PMID- 17190526
TI  - Neurotensin agonists: potential in the treatment of schizophrenia.
AB  - Neurotensin (NT) is a neuropeptide that, for decades, has been implicated in the
      biology of schizophrenia. It is closely associated with, and is thought to
      modulate, dopaminergic and other neurotransmitter systems involved in the
      pathophysiology of various neuropsychiatric diseases, including schizophrenia.
      This review outlines the neurochemistry and function of the NT system and the
      data implicating its role in schizophrenia. The data suggest that NT receptor
      agonists have the potential to be used as novel therapeutic agents for the
      treatment of schizophrenia, with the added benefits of (i) not causing weight
      gain, an adverse effect that is problematic with some of the currently used
      atypical antipsychotic drugs; and (ii) helping patients to stop smoking, a
      behaviour that is highly prevalent in those with schizophrenia.

PMID- 17190527
TI  - Restarting clozapine after neutropenia: evaluating the possibilities and
      practicalities.
AB  - Clozapine remains the antipsychotic of choice for refractory schizophrenia
      despite its propensity for serious blood disorders. When neutropenia or
      agranulocytosis occur in people taking clozapine, cessation of treatment is
      mandated and relapse often results. Because such patients are usually
      unresponsive to other antipsychotics, many clinicians consider restarting
      clozapine, despite the risks involved. However, the risks of clozapine
      rechallenge vary according to the cause and nature of the blood dyscrasia.
      Neutropenia can arise because of factors unrelated or indirectly related to
      clozapine treatment. These include benign ethnic neutropenia, concomitant drug
      therapy, co-existing medical conditions and drug interactions. In such cases,
      clozapine may be restarted if non-clozapine causes of neutropenia are identified
      and eliminated, although concurrent treatment with lithium (to induce
      leukocytosis) is sometimes necessary. Close monitoring of the patient is
      essential because it is rarely possible to completely rule out the contribution
      of clozapine to the blood dyscrasia and because lithium does not protect against
      clozapine-related agranulocytosis. In cases of clozapine-induced neutropenia (as
      distinct from agranulocytosis, which may have a different pathology) rechallenge
      may also be considered and, again, lithium co-therapy may be required. Where
      clozapine is clearly the cause of agranulocytosis, rechallenge should not be
      considered or undertaken unless there are very exceptional circumstances (severe
      and prolonged relapse following clozapine discontinuation). In these cases, re
      exposure to clozapine may rarely be attempted where there are facilities for very
      close and frequent monitoring. Granulocyte colony-stimulating factor is likely to
      be required as co-therapy, given the very high likelihood of recurrence.
      Uncertainty over the likely cause of blood dyscrasia in people taking clozapine,
      coupled with uncertainty over the mechanism by which clozapine causes both
      neutropenia and agranulocytosis, makes any attempt to restart clozapine a high
      risk venture requiring the utmost caution.

PMID- 17190531
TI  - Extended-release intramuscular naltrexone in alcohol dependence in adults:
      profile report.

PMID- 17190530
TI  - Use of the sustained pain-free plus no adverse events endpoint in clinical trials
      of triptans in acute migraine.
AB  - OBJECTIVE: To assess the relationship between the sustained pain free (SPF) and
      adverse event (AE) rates associated with six oral serotonin 5-HT(1B/1D) receptor
      agonists (triptans) used for the treatment of acute migraine, employing data from
      a previous meta-analysis (that included almotriptan, eletriptan, naratriptan,
      rizatriptan, sumatriptan and zolmitriptan, but not frovatriptan) in order to
      provide a rationale for the use of the rate of patients who are SPF plus no AE
      (SNAE) as an endpoint in trials of medications for acute migraine. BACKGROUND:
      The attributes of drug treatment for acute migraine that are most important to
      people who experience them are complete pain relief, lack of recurrence, rapid
      onset and lack of AEs. The endpoints used to assess therapy for acute migraine do
      not always address these elements. METHODS: The relationship between SPF and AE
      rates was explored using nonparametric regression techniques, and the box-plot
      method was used to identify outliers. The estimated SNAE rate for each triptan
      was calculated with and without assuming independence between efficacy and
      tolerability. RESULTS: At the level of the individual agent, there was a
      significant relationship between the efficacy and tolerability of each triptan,
      with the exception of almotriptan 12.5 mg, which had an AE rate approximately 30%
      lower than would be expected, and eletriptan 20 mg, which had an AE rate
      approximately 20% higher than would be expected, on the basis of their efficacy.
      Almotriptan 12.5 mg and eletriptan 20 mg had the highest and lowest base-case
      values for SNAE, respectively, and both qualified statistically as outliers to
      the distribution of SNAE values obtained with the other triptans. The probability
      that each triptan was superior to the reference agent (sumatriptan 100 mg) in
      terms of SNAE was calculated across all possible values (at the level of the
      individual patient) for the relationship between efficacy and tolerability.
      Again, almotriptan 12.5 mg and eletriptan 20 mg had the highest and lowest values
      for their SNAE rates, respectively, and almotriptan 12.5 mg qualified
      statistically as an outlier from the distribution of the probabilities obtained
      for the other triptans. CONCLUSION: This analysis determined that higher SPF
      rates were strongly associated with higher AE rates, with the notable exception
      of almotriptan 12.5 mg, which had a lower than expected AE rate, resulting in the
      highest SNAE rate of the included triptans and doses. SNAE is a useful measure
      that can be used to discriminate between therapies and this endpoint incorporates
      the attributes that are most relevant to patient satisfaction with treatment. We
      recommend calculation of the SNAE rate at the level of the individual patient in
      future clinical trials of medication for the treatment of acute migraine to
      facilitate selection of a treatment for acute migraine that offers the best
      chance for effective management.

PMID- 17190529
TI  - Thirty years of clinical experience with carbamazepine in the treatment of
      bipolar illness: principles and practice.
AB  - Carbamazepine began to be studied in a systematic fashion in the 1970s and became
      more widely used in the treatment of bipolar disorder in the 1980s. Interest in
      carbamazepine has been renewed by (i) the recent US FDA approval of a long-acting
      preparation for the treatment of acute mania; (ii) studies suggesting some
      efficacy in bipolar depression; and (iii) evidence of prophylactic efficacy in
      some difficult-to-treat subtypes of bipolar illness. A series of double-blind
      controlled studies of the drug were conducted at the US National Institute of
      Mental Health from the mid-1970s to the mid-1990s. This review summarises our
      experience in the context of the current literature on the clinical efficacy,
      adverse effects and pharmacokinetic interactions of carbamazepine. Carbamazepine
      has an important and still evolving place in the treatment of acute mania and
      long-term prophylaxis. It may be useful in individuals with symptoms that are not
      responsive to other treatments and in some subtypes of bipolar disorder that are
      not typically responsive to a more traditional agent such as lithium. These
      subtypes might include those patients with bipolar II disorder, dysphoric mania,
      substance abuse co-morbidity, mood incongruent delusions, and a negative family
      history of bipolar illness in first-degree relatives. In addition, carbamazepine
      may be useful in patients who do not adequately tolerate other interventions as a
      result of adverse effects, such as weight gain, tremor, diabetes insipidus or
      polycystic ovarian syndrome. We review our clinical and research experience with
      carbamazepine alone and in combination with lithium, valproic acid and other
      agents in complex combination treatment of bipolar illness. More precise clinical
      and biological predictors and correlates of individual clinical responsiveness to
      carbamazepine and other mood stabilisers are eagerly awaited.

PMID- 17190532
TI  - Cross education: possible mechanisms for the contralateral effects of unilateral
      resistance training.
AB  - Resistance training can be defined as the act of repeated voluntary muscle
      contractions against a resistance greater than those normally encountered in
      activities of daily living. Training of this kind is known to increase strength
      via adaptations in both the muscular and nervous systems. While the physiology of
      muscular adaptations following resistance training is well understood, the nature
      of neural adaptations is less clear. One piece of indirect evidence to indicate
      that neural adaptations accompany resistance training comes from the phenomenon
      of 'cross education', which describes the strength gain in the opposite,
      untrained limb following unilateral resistance training. Since its discovery in
      1894, subsequent studies have confirmed the existence of cross education in
      contexts involving voluntary, imagined and electrically stimulated contractions.
      The cross-education effect is specific to the contralateral homologous muscle but
      not restricted to particular muscle groups, ages or genders. A recent meta
      analysis determined that the magnitude of cross education is approximately equal
      to 7.8% of the initial strength of the untrained limb. While many features of
      cross education have been established, the underlying mechanisms are unknown.
      This article provides an overview of cross education and presents plausible
      hypotheses for its mechanisms. Two hypotheses are outlined that represent the
      most viable explanations for cross education. These hypotheses are distinct but
      not necessarily mutually exclusive. They are derived from evidence that high
      force, unilateral, voluntary contractions can have an acute and potent effect on
      the efficacy of neural elements controlling the opposite limb. It is possible
      that with training, long-lasting adaptations may be induced in neural circuits
      mediating these crossed effects. The first hypothesis suggests that unilateral
      resistance training may activate neural circuits that chronically modify the
      efficacy of motor pathways that project to the opposite untrained limb. This may
      subsequently lead to an increased capacity to drive the untrained muscles and
      thus result in increased strength. A number of spinal and cortical circuits that
      exhibit the potential for this type of adaptation are considered. The second
      hypothesis suggests that unilateral resistance training induces adaptations in
      motor areas that are primarily involved in the control of movements of the
      trained limb. The opposite untrained limb may access these modified neural
      circuits during maximal voluntary contractions in ways that are analogous to
      motor learning. A better understanding of the mechanisms underlying cross
      education may potentially contribute to more effective use of resistance training
      protocols that exploit these cross-limb effects to improve the recovery of
      patients with movement disorders that predominantly affect one side of the body.

PMID- 17190535
TI  - Power athletes and distance training: physiological and biomechanical rationale
      for change.
AB  - The development of power lies at the foundation of all movement, especially
      athletic performance. Unfortunately, training programmes of athletes often seek
      to improve cardiovascular endurance through activities such as distance training
      that are detrimental for the performance of power athletes, rather than using
      other means of exercise. Performance decrements from continuous aerobic training
      can be a result of inappropriate neuromuscular adaptations, a catabolic hormonal
      profile, an increased risk for overtraining and an ineffective motor learning
      environment. However, long, sustained exercise continues to be employed at all
      levels of competition to obtain benefits that could be achieved more effectively
      through other forms of conditioning. While some advantageous effects of endurance
      training may occur, there are unequivocal drawbacks to distance training in the
      power athlete. There are many other types of conditioning that are more relevant
      to all anaerobic sports and will also avoid the negative consequences associated
      with distance training.

PMID- 17190534
TI  - The effects of exercise training on fat-mass loss in obese patients during energy
      intake restriction.
AB  - Dietary restriction combined with endurance exercise training represents an
      effective strategy to promote weight loss and reduce fat mass in obese patients.
      Exercise programmes without dietary restriction are less efficient. However,
      addition of exercise to a dietary restriction programme does not induce a greater
      fat-mass loss than dietary restriction alone. The latter is likely attributed to
      a compensatory reduction in daily physical activity following the implementation
      of exercise training. Nonetheless, inclusion of an exercise training programme is
      important to prevent a decrease in fat-free mass, increase relative visceral fat
      mass loss, improve dietary compliance and eventually maintain long-term weight
      control. Obese male patients with the highest fat mass are most likely to lose
      the largest amount of fat mass in such lifestyle intervention programmes.
      Influences of training modalities during energy intake restriction on fat-mass
      loss are reviewed. The relationship between total energy expenditure during
      exercise training and overall fat-mass loss has been firmly established. The
      amount of training forms a more important predictor of fat-mass loss than
      training intensity. The sort of exercise (e.g. walking, cycling, swimming) plays
      another important predictor of fat-mass loss in intervention programmes. The
      implementation of resistance training in such programmes does not augment fat
      mass loss but improves body composition by increasing fat-free mass. Further
      studies are needed to define the optimal interventional programme for obese
      patients.

PMID- 17190533
TI  - Cardiac tissue Doppler imaging in sports medicine.
AB  - The differentiation of training-induced cardiac adaptations from pathological
      conditions is a key issue in sports cardiology. As morphological features do not
      allow for a clear delineation of early stages of relevant pathologies, the
      echocardiographic evaluation of left ventricular function is the technique of
      first choice in this regard. Tissue Doppler imaging (TDI) is a relatively recent
      method for the assessment of cardiac function that provides direct, local
      measurements of myocardial velocities throughout the cardiac cycle. Although it
      has shown a superior sensitivity in the detection of ventricular dysfunction in
      clinical and experimental studies, its application in sports medicine is still
      rare. Besides technical factors, this may be due to a lack in consensus on the
      characteristics of ventricular function in relevant conditions. For more than two
      decades there has been an ongoing debate on the existence of a supernormal left
      ventricular function in athlete's heart. While results from traditional
      echocardiography are conflicting, TDI studies established an improved diastolic
      function in endurance-trained athletes with athlete's heart compared with
      controls.The influence of anabolic steroids on cardiac function also has been
      investigated by standard echocardiographic techniques with inconsistent results.
      The only TDI study dealing with this topic demonstrated a significantly impaired
      diastolic function in bodybuilders with long-term abuse of anabolic steroids
      compared with strength-trained athletes without abuse of anabolic steroids and
      controls, respectively.Hypertrophic cardiomyopathy is the most frequent cause of
      sudden death in young athletes. However, in its early stages, it is difficult to
      distinguish from athlete's heart. By means of TDI, ventricular dysfunction in
      hypertrophic cardiomyopathy can be disclosed even before the development of left
      ventricular hypertrophy. Also, a differentiation of left ventricular hypertrophy
      due to hypertrophic cardiomyopathy or systemic hypertension is possible by TDI.
      Besides the evaluation of different forms of left ventricular hypertrophy, the
      diagnosis of myocarditis is also of particular importance in athletes. Today, it
      still requires myocardial biopsy. The analysis of focal disturbances in
      myocardial velocities might be a promising non-invasive method; however,
      systematic validation studies are lacking. An important future issue for the
      implementation of TDI into routine examination will be the standardisation of
      procedures and the establishment of significant reference values for the above
      mentioned conditions. Innovative TDI parameters also merit further investigation.

PMID- 17190536
TI  - The physiology of mountain biking.
AB  - Mountain biking is a popular outdoor recreational activity and an Olympic sport.
      Cross-country circuit races have a winning time of approximately equal 120
      minutes and are performed at an average heart rate close to 90% of the maximum,
      corresponding to 84% of maximum oxygen uptake (VO2max). More than 80% of race
      time is spent above the lactate threshold. This very high exercise intensity is
      related to the fast starting phase of the race; the several climbs, forcing off
      road cyclists to expend most of their effort going against gravity; greater
      rolling resistance; and the isometric contractions of arm and leg muscles
      necessary for bike handling and stabilisation. Because of the high power output
      (up to 500W) required during steep climbing and at the start of the race,
      anaerobic energy metabolism is also likely to be a factor of off-road cycling and
      deserves further investigation. Mountain bikers' physiological characteristics
      indicate that aerobic power (VO2max >70 mL/kg/min) and the ability to sustain
      high work rates for prolonged periods of time are prerequisites for competing at
      a high level in off-road cycling events. The anthropometric characteristics of
      mountain bikers are similar to climbers and all-terrain road cyclists. Various
      parameters of aerobic fitness are correlated to cross-country performance,
      suggesting that these tests are valid for the physiological assessment of
      competitive mountain bikers, especially when normalised to body mass. Factors
      other than aerobic power and capacity might influence off-road cycling
      performance and require further investigation. These include off-road cycling
      economy, anaerobic power and capacity, technical ability and pre-exercise
      nutritional strategies.

PMID- 17190538
TI  - Observation of the d3Pi(g)<--c3Sigma(u)+ band system of C2.
AB  - A new band system of C(2), d (3)Pi(g)<--c (3)Sigma(u) (+) is observed by laser
      induced fluorescence spectroscopy, constituting the first direct detection of the
      c (3)Sigma(u) (+) state of C(2). Observations were made by laser excitation of c
      (3)Sigma(u) (+)(v(")=0) C(2), produced in an acetylene discharge, to the d
      (3)Pi(g)(v(')=3) level, followed by detection of Swan band fluorescence.
      Rotational analysis of this band yielded rotational constants for the c
      (3)Sigma(u) (+)(v(")=0) state: B(0)=1.9218(2) cm(-1), lambda(0)=-0.335(4) cm(-1)
      and gamma(0)=0.011(2) cm(-1). The vibrational band origin was determined to be
      nu(3-0)=15861.28 cm(-1).

PMID- 17190540
TI  - Bohmian mechanics with complex action: a new trajectory-based formulation of
      quantum mechanics.
AB  - In recent years there has been a resurgence of interest in Bohmian mechanics as a
      numerical tool because of its local dynamics, which suggest the possibility of
      significant computational advantages for the simulation of large quantum systems.
      However, closer inspection of the Bohmian formulation reveals that the
      nonlocality of quantum mechanics has not disappeared-it has simply been swept
      under the rug into the quantum force. In this paper we present a new formulation
      of Bohmian mechanics in which the quantum action, S, is taken to be complex. This
      leads to a single equation for complex S, and ultimately complex x and p but
      there is a reward for this complexification-a significantly higher degree of
      localization. The quantum force in the new approach vanishes for Gaussian wave
      packet dynamics, and its effect on barrier tunneling processes is orders of
      magnitude lower than that of the classical force. In fact, the current method is
      shown to be a rigorous extension of generalized Gaussian wave packet dynamics to
      give exact quantum mechanics. We demonstrate tunneling probabilities that are in
      virtually perfect agreement with the exact quantum mechanics down to 10(-7)
      calculated from strictly localized quantum trajectories that do not communicate
      with their neighbors. The new formulation may have significant implications for
      fundamental quantum mechanics, ranging from the interpretation of non-locality to
      measures of quantum complexity.

PMID- 17190539
TI  - Toward the understanding of DNA fluorescence: the singlet excimer of cytosine.
AB  - By using the multiconfigurational second-order perturbation method CASPT2,
      including corrections for the basis set superposition error, the lowest-singlet
      excited state of the face-to-face pi-stacked cytosine homodimer is revealed to be
      bound by about half an eV, being the source of an emissive feature consistent
      with the observed redshifted fluorescence.

PMID- 17190541
TI  - Study of static and dynamic first hyperpolarizabilities using time-dependent
      density functional quadratic response theory with local contribution and natural
      bond orbital analysis.
AB  - We apply time-dependent density-functional quadratic response theory to
      investigate the static and dynamic second-order polarizabilities (first
      hyperpolarizability) beta. A new implementation using Slater-type basis
      functions, numerical integration, and density fitting techniques is reported. The
      second order coupled perturbed Kohn-Sham equations are solved and the second
      order perturbed charge density is obtained. It is useful to highlight atomic and
      bond contributions to understand the relation between molecular structure and
      properties. Four moderately sized molecules (para-nitroaniline and derivatives
      thereof) are investigated to assess the accuracy of the time-dependent density
      functional theory computations and to investigate the distribution of the second
      order charge density as well as the "beta density." Our results highlight the
      contributions from atoms and bonds on different functional groups to the total
      value of beta with Mulliken-type and natural bond orbital (NBO) analyses, and
      demonstrate in some cases how contributions from a particular bond may be
      identified easily by visual inspection of the beta density. In addition, the
      position of side group substitution on carbon-carbon bonds significantly affects
      the hyperpolarizability. A contribution analysis as performed here might be
      helpful for the design of new materials with desired properties.

PMID- 17190542
TI  - Electron correlation in the 3 (1)Sigma(g)+ and 2 (1)Sigma(u)+ excited state
      lithium molecule.
AB  - Electron correlation effects in the two excited states of Li(2), 3 (1)Sigma(g)
      (+) and 2 (1)Sigma(u) (+), one with a shelf shape and another with double minima
      in their potential energy curves, have been studied with the aid of the
      calculated electron pair density distribution as a function of the internuclear
      distance and the analysis of the natural orbitals. Both states show increased
      electron pair densities at intermediate interelectronic distances around the
      second minimum of their potential energy curves. Since the bond breaks
      homolitically this observation runs contrary to regular expectations. Analysis of
      the electron pair density distributions and the natural orbitals provides
      mechanisms to account for this abnormal behavior.

PMID- 17190543
TI  - Phase-sensitive stimulated Raman adiabatic passage in dipolar extended lambda
      systems.
AB  - The authors investigate the possible phase-sensitive behavior of (multiphoton)
      stimulated Raman adiabatic passage population transfer in extended lambda
      systems, if more than one state of an anharmonic progression of target levels is
      accessible in transitions of different photonicities. They use a minimal model
      four-level system (4LS) with one initial state separated from two target states
      by an apex state. The parameters of the 4LS are adapted from the bend states of
      the HCN-HNC system. Using a dressed-state analysis within the rotating wave
      approximation (RWA), the authors identify phase-dependent diabatic transitions
      between the two dressed states contributing to the state vector as the mechanism
      leading to phase-sensitive target populations. The essential features giving rise
      to the phase dependence are found to be different (non-zero-) diagonal elements
      of the dipole matrix, i.e., permanent dipole moments, and the presence of a
      direct two-photon overtone coupling between the apex state and the lower target
      state which formally enters the RWA Hamiltonian upon inclusion of permanent
      dipole moments. Among the parameters controlling the extent of the effect are the
      anharmonic properties of the target progression and the absolute values of the
      field frequencies, so that in view of the requirement to tune the driving fields
      into the vicinity of resonance, details of the level structure are of importance.
      A comparative numerical study executed without invoking RWA shows that
      qualitatively there are similar trends in the appearance of phase sensitivity,
      although the effects are considerably more pronounced in the full treatment. In
      the full treatment the authors also explore off-resonance conditions and discuss
      the signatures of phase sensitivity in the target populations.

PMID- 17190544
TI  - Testing the TPSS meta-generalized-gradient-approximation exchange-correlation
      functional in calculations of transition states and reaction barriers.
AB  - We have studied the performance of local and semilocal exchange-correlation
      functionals [meta-generalized-gradient-approximation (GGA)-TPSS, GGA-Perdew-Burke
      Ernzerhof (PBE), and local density approximation (LDA)] in the calculation of
      transition states, reaction energies, and barriers for several molecular and one
      surface reaction, using the plane-wave pseudopotential approach. For molecular
      reactions, these results have been compared to all-electron Gaussian calculations
      using the B3LYP hybrid functional, as well as to experiment and high level
      quantum chemistry calculations, when available. We have found that the transition
      state structures are accurately identified irrespective of the level of the
      exchange-correlation functional, with the exception of a qualitatively incorrect
      LDA prediction for the H-transfer reaction in the hydrogen bonded complex between
      a water molecule and a OH radical. Both the meta-GGA-TPSS and the GGA-PBE
      functionals improve significantly the calculated LDA barrier heights. The meta
      GGA-TPSS further improves systematically, albeit not always sufficiently, the GGA
      PBE barriers. We have also found that, on the Si(001) surface, the meta-GGA-TPSS
      barriers for hydrogen adsorption agree significantly better than the
      corresponding GGA-PBE barriers with quantum Monte Carlo cluster results and
      experimental estimates.

PMID- 17190545
TI  - Combined density functional/polarizable continuum model study of magnetochiral
      birefringence: can theory and experiment be brought to agreement?
AB  - The magnetic-field-induced axial birefringence (magnetochirality) of five closed
      shell chiral molecules (three substituted oxiranes, carvone, and limonene) is
      studied at the density functional theory level using Becke's 3-parameter Lee-Yang
      Parr functional and frequency-dependent quadratic response theory. The influence
      of the environment and the conformational distribution on the property is also
      studied. The environment effects are described by the polarizable continuum model
      in its integral-equation formulation. The effect of the conformational
      distribution is investigated by performing calculations on several conformers-for
      carvone and limonene-followed by Boltzmann averaging. The calculated values for
      the magnetochiral birefringence are compared to previous ab initio results and
      experimental data where available. The refined model presented here brings the ab
      initio values closer to experiment. Still, disagreements remain in some cases and
      it appears difficult to resolve these discrepancies.

PMID- 17190546
TI  - Insertion of rare gas atoms into BF3 and AlF3 molecules: an ab initio
      investigation.
AB  - The structure, stability, charge redistribution, and harmonic vibrational
      frequencies of rare gas inserted group III-B fluorides with the general formula F
      Rg-MF(2) (where M=B and Al; Rg=Ar, Kr, and Xe) have been investigated using ab
      initio quantum chemical methods. The Rg atom is inserted in one of the M-F bond
      of MF(3) molecules, and the geometries are optimized for ground as well as
      transition states using the MP2 method. It has been found that Rg inserted F-Rg-M
      portion is linear in both F-Rg-BF(2) and F-Rg-AlF(2) species. The binding
      energies corresponding to the lowest energy fragmentation products MF(3)+Rg (two
      body dissociation) have been computed to be -670.4, -598.8, -530.7, -617.0, 
      562.1, and -494.0 kJmol for F-Ar-BF(2), F-Kr-BF(2), F-Xe-BF(2), F-Ar-AlF(2), F-Kr
      AlF(2), and F-Xe-AlF(2) species, respectively. The dissociation energies
      corresponding to MF(2)+Rg+F fragments (three-body dissociation) are found to be
      positive with respect to F-Rg-MF(2) species, and the computed values are 56.3,
      127.8, and 196.0 kJmol for F-Ar-BF(2), F-Kr-BF(2), and F-Xe-BF(2) species,
      respectively. The corresponding values for F-Ar-AlF(2), F-Kr-AlF(2), and F-Xe
      AlF(2) species are also found to be positive. The decomposition of F-Rg-MF(2)
      species into the MF(3)+Rg (two-body dissociation) channel typically proceeds via
      a transition state involving F-Rg-M out-of-plane bending mode. The transition
      state barrier heights are 35.5, 62.7, 89.8, 22.0, 45.6, and 75.3 kJmol for F-Ar
      BF(2), F-Kr-BF(2), F-Xe-BF(2), F-Ar-AlF(2), F-Kr-AlF(2), and F-Xe-AlF(2) species,
      respectively. The calculated geometrical parameters and the energy values suggest
      that these species are metastable and may be prepared and characterized using low
      temperature matrix isolation techniques, and are possibly the next new candidates
      for gas phase or matrix experiments.

PMID- 17190537
TI  - A systematic review on ankle injury and ankle sprain in sports.
AB  - This article systematically reviews epidemiological studies on sports injury from
      1977 to 2005 in which ankle injury was included. A total of 227 studies reporting
      injury pattern in 70 sports from 38 countries were included. A total of 201,600
      patients were included, with 32,509 ankle injuries. Ankle injury information was
      available from 14,098 patients, with 11 847 ankle sprains. Results show that the
      ankle was the most common injured body site in 24 of 70 included sports,
      especially in aeroball, wall climbing, indoor volleyball, mountaineering, netball
      and field events in track and field. Ankle sprain was the major ankle injury in
      33 of 43 sports, especially in Australian football, field hockey, handball,
      orienteering, scooter and squash. In sports injuries throughout the countries
      studied, the ankle was the second most common injured body site after the knee,
      and ankle sprain was the most common type of ankle injury. The incidence of ankle
      injury and ankle sprain was high in court games and team sports, such as rugby,
      soccer, volleyball, handball and basketball. This systematic review provides a
      summary of the epidemiology of ankle injury in sports.

PMID- 17190547
TI  - Efficient formulation and computer implementation of the active-space electron
      attached and ionized equation-of-motion coupled-cluster methods.
AB  - The efficient, general-purpose implementations of the active-space electron
      attached (EA) and ionized (IP) equation-of-motion coupled-cluster (EOMCC) methods
      including up to 3p-2h and 3h-2p excitations, called EA-EOMCCSDt and IP-EOMCCSDt,
      respectively, are discussed. The details of the algorithm that enables one to
      achieve a high degree of code vectorization for the active-space methods and the
      factorized forms of the EA- and IP-EOMCCSDt equations that maximize the benefits
      of using active orbitals in the process of selecting the dominant 3p-2h and 3h-2p
      excitations are presented. The results of benchmark calculations for the low
      lying doublet and quartet states of the CH and SH radicals reveal that the active
      space EA-EOMCCSDt and IP-EOMCCSDt methods are capable of producing results for
      the electronic excitations in open-shell systems that match the high accuracy of
      EA- and IP-EOMCC calculations with a full treatment of 3p-2h and 3h-2p
      excitations, even when the excited states of interest display a manifestly
      multideterminantal nature, with the costs that can be on the same order of those
      characterizing the basic EOMCC singles and doubles approach.

PMID- 17190548
TI  - Time-dependent density-functional theory beyond the adiabatic approximation:
      insights from a two-electron model system.
AB  - Most applications of time-dependent density-functional theory (TDDFT) use the
      adiabatic local-density approximation (ALDA) for the dynamical exchange
      correlation potential V(xc)(r,t). An exact (i.e., nonadiabatic) extension of the
      ground-state LDA into the dynamical regime leads to a V(xc)(r,t) with a memory,
      which causes the electron dynamics to become dissipative. To illustrate and
      explain this nonadiabatic behavior, this paper studies the dynamics of two
      interacting electrons on a two-dimensional quantum strip of finite size,
      comparing TDDFT within and beyond the ALDA with numerical solutions of the two
      electron time-dependent Schrodinger equation. It is shown explicitly how
      dissipation arises through multiple particle-hole excitations, and how the
      nonadiabatic extension of the ALDA fails for finite systems but becomes correct
      in the thermodynamic limit.

PMID- 17190549
TI  - Assessment of a long-range corrected hybrid functional.
AB  - Common approximate exchange-correlation functionals suffer from self-interaction
      error, and as a result, their corresponding potentials have incorrect asymptotic
      behavior. The exact asymptote can be imposed by introducing range separation into
      the exchange component and replacing the long-range portion of the approximate
      exchange by the Hartree-Fock counterpart. The authors show that this long-range
      correction works particularly well in combination with the short-range variant of
      the Perdew-Burke-Ernzerhof (PBE) exchange functional. This long-range-corrected
      hybrid, here denoted LC-omegaPBE, is remarkably accurate for a broad range of
      molecular properties, such as thermochemistry, barrier heights of chemical
      reactions, bond lengths, and most notably, description of processes involving
      long-range charge transfer.

PMID- 17190550
TI  - The relativistic complete active-space second-order perturbation theory with the
      four-component Dirac Hamiltonian.
AB  - The relativistic complete active-space second-order perturbation theory (CASPT2)
      is developed for the four-component relativistic Hamiltonian. The present method
      can describe the near-degenerated and dissociated electronic states of molecules
      involving atoms of heavy elements. The present approach is less expensive than
      the relativistic multireference configuration interaction method. The ground and
      low-lying excited states of TlH, Tl(2), and PtH molecules are calculated with the
      Dirac-Coulomb (DC) CASPT2 method and their spectroscopic constants are obtained.
      These spectroscopic constants are compared with experimental findings and
      previous theoretical work. For all the molecules, the spectroscopic constants of
      DC-CASPT2 show good agreement with the experimental or previous theoretical
      spectroscopic constants. The present theory provides accurate descriptions of
      bonding or dissociation states and of ground and excited states in a well
      balanced way.

PMID- 17190551
TI  - Density-functional theory with effective potential expressed as a direct mapping
      of the external potential: applications to atomization energies and ionization
      potentials.
AB  - In this paper the authors further develop and apply the direct-mapping density
      functional theory to calculations of the atomization energies and ionization
      potentials. Single-particle orbitals are determined by solving the Kohn-Sham
      [Phys. Rev. A. 140, 1133 (1965)] equations with a local effective potential
      expressed in terms of the external potential. A two-parametric form of the
      effective potential for molecules is proposed and equations for optimization of
      the parameters are derived using the exchange-only approximation. Orbital
      dependent correlation functional is derived from the second-order perturbation
      theory in its Moller-Plesset-type zeroth-order approximation based on the Kohn
      Sham orbitals and orbital energies. The total atomization energies and ionization
      potentials computed with the second-order perturbation theory were found to be in
      agreement with experimental values and benchmark results obtained with ab initio
      wave mechanics methods.

PMID- 17190552
TI  - Towards a highly efficient theoretical treatment of Jahn-Teller effects in
      molecular spectra: the 1 2A and 2 2A electronic states of the ethoxy radical.
AB  - Nonadiabatic effects in the two lowest electronic states of the ethoxy radical,
      the 1 (2)A and 2 (2)A states, are considered, using multireference configuration
      interaction (MRCI) wave functions comprised of over 15x10(6) configuration state
      functions. The lowest point on the seam of conical intersection is located. Using
      this point as the origin, a quasidiabatic Hamiltonian suitable for use in a
      multimode vibronic coupling treatment of the coupled 1 (2)A and 2 (2)A electronic
      states is determined. The Hamiltonian includes all contributions from all
      internal coordinates through second order in displacements from the origin and is
      comprised of over 500 parameters. By using the average energy gradient, the
      energy difference gradients, and the derivative couplings, all of which are
      obtained at little additional cost once the requisite eigenstates are known, the
      second order Hamiltonian is determined from MRCI calculations at only 35 nuclear
      configurations. This is essentially the same number of points required to obtain
      the frequencies for the ground state equilibrium structure using centered
      differences of gradients. The diabatic Hamiltonian provides a good description of
      the seam space, the (N(int)-2)-dimensional space of conical intersection points,
      continuously connected to the minimum energy crossing point, enabling, for the
      first time, an analysis of the changes in the branching plane induced by seam
      curvature in the full seam space. Comparing the diabatic representation and MRCI
      results we find a good agreement for the ground state equilibrium structure,
      R(eq)(1 (2)A), as well as the ground state energy and vertical excitation energy.
      In good agreement with the available experimental data are the ground state
      equilibrium structure and the excitation energy to the A (2)A state, predicted
      here to involve a cone state level. Agreement between the harmonic frequencies at
      R(eq)(1 (2)A) computed from the MRCI wave function and from the diabatic
      Hamiltonian is excellent for all but the three lowest energy normal modes where
      significant deviations are observed indicating the need for selected cubic and/or
      quartic terms. For the low-lying vibrational levels, the diabatic representation
      can be used to partition the normal modes into two groups, those that involve
      inter(diabatic) state coupling and those that are spectators as far as
      nonadiabatic effects are concerned. The spin-orbit coupling interaction is
      determined using the Breit-Pauli approximation and its incorporation into the
      diabatic Hamiltonian is discussed.

PMID- 17190553
TI  - 1B2(1Sigma(u)+) excited state decay dynamics in CS2.
AB  - The authors report time resolved photoelectron spectra of the (1)B(2)((1)Sigma(u)
      (+)) state of CS(2) at pump wavelengths in the region of 200 nm. In contrast to
      previous studies, the authors find that the predissociation dynamics is not well
      described by a single exponential decay. Biexponential modeling of the authors'
      data reveals a rapid decay pathway (tau<50 fs), in addition to a longer lived
      channel (tau approximately 350-650 fs) that displays a marked change in apparent
      lifetime when the polarization of the pump laser is rotated with respect to that
      of the probe. Since the initially populated (1)B(2)((1)Sigma(u) (+)) state may
      decay to form either S((1)D) or S((3)P) products (the latter produced via a spin
      orbit induced crossing from a singlet to a triplet electronic surface), this
      lifetime observation may be rationalized in terms of changes in the relative
      ionization cross section of these singlet and triplet states of CS(2) as a
      function of laser polarization geometry. The experimentally observed lifetime of
      the longer lived channel is therefore a superposition of these two pathways, both
      of which decay on very similar time scales.

PMID- 17190554
TI  - Evidence of the formation and conversion of unstable thionyl isocyanate: Gas
      phase spectroscopic studies.
AB  - Thionyl diisocyanate which is unstable at ambient temperature is generated from a
      heterogeneous reaction of gaseous thionyl dichloride with silver cyanate and
      studied for the first time in the gas phase at 298 K. N-isocyanatoformyl
      sulfinylimide is also observed with photoelectron spectroscopy in the gas phase
      for the first time. The conversion of thionyl diisocyanate to N-isocyanatoformyl
      sulfinylimide via 1,3 shift at different temperatures is studied by using
      photoelectron spectroscopy and mass spectroscopy with the help of theoretical
      computations. On the basis of combined observations and quantum chemical
      calculations, possible 1,3-isocyanato shifts and dissociation processes for
      thionyl isocyanate and its cation have been discussed in detail.

PMID- 17190555
TI  - Complex self-consistent field and multireference single- and double-excitation
      configuration interaction calculations for the 2Pi(g) resonance state of N2-.
AB  - Self-consistent field and multireference single- and double-excitation
      configuration interaction calculations employing the complex basis function
      technique are carried out for the (2)Pi(g) resonance state of the N(2) (-)
      molecule as well as several other anionic resonance states in the neighboring
      energy region. The results of calculations employing the same method for the (1)S
      (2s(2)) state of the He atom and the (1)Sigma(g) (+) (sigma(u) (2)) state of the
      H(2) molecule are found to be in good agreement with those of earlier work. The
      present theoretical treatment has succeeded for the first time in satisfying the
      rigorous criterion of the complex variational principle in computing the N(2) (-)
      resonance states, namely, a cusp in the plots of real versus imaginary components
      of the corresponding complex energies has been located at each internuclear
      distance. On this basis, it is found that the open-shell orbital in the lowest
      energy adiabatic N(2) (-) resonance state of (2)Pi(g) symmetry changes its
      character from quite compact at large internuclear distance to relatively diffuse
      for r<2.3a(0). This is in contrast to all previous theoretical treatments of this
      system that have not rigorously satisfied the complex variational principle in
      their determination of this wave function.

PMID- 17190556
TI  - Structure and spectral features of H+(H2O)7: Eigen versus Zundel forms.
AB  - The two dimensional (2D) to three dimensional (3D) transition for the protonated
      water cluster has been controversial, in particular, for H(+)(H(2)O)(7). For
      H(+)(H(2)O)(7) the 3D structure is predicted to be lower in energy than the 2D
      structure at most levels of theory without zero-point energy (ZPE) correction. On
      the other hand, with ZPE correction it is predicted to be either 2D or 3D
      depending on the calculational levels. Although the ZPE correction favors the 3D
      structure at the level of coupled cluster theory with singles, doubles, and
      perturbative triples excitations [CCSD(T)] using the aug-cc-pVDZ basis set, the
      result based on the anharmonic zero-point vibrational energy correction favors
      the 2D structure. Therefore, the authors investigated the energies based on the
      complete basis set limit scheme (which we devised in an unbiased way) at the
      resolution of the identity approximation Moller-Plesset second order perturbation
      theory and CCSD(T) levels, and found that the 2D structure has the lowest energy
      for H(+)(H(2)O)(7) [though nearly isoenergetic to the 3D structure for
      D(+)(D(2)O)(7)]. This structure has the Zundel-type configuration, but it shows
      the quantum probabilistic distribution including some of the Eigen-type
      configuration. The vibrational spectra of MP2/aug-cc-pVDZ calculations and Car
      Parrinello molecular dynamics simulations, taking into account the thermal and
      dynamic effects, show that the 2D Zundel-type form is in good agreement with
      experiments.

PMID- 17190557
TI  - Sensitivity of photoelectron circular dichroism to structure and electron
      dynamics in the photoionization of carvone and related chiral monocyclic
      terpenone enantiomers.
AB  - The photoelectron circular dichroism that arises in the angular distribution of
      photoelectrons emitted from the carbonyl group in randomly oriented pure
      enantiomers of carvone, and a number of carvone derivatives, is investigated by
      continuum multiple scattering calculations. Core ionization of carbonyl C 1s
      orbitals is examined for six different isopropenyl tail conformations of carvone.
      These show clear differences of behavior both between axial and equatorial
      conformations, and between the three rotational conformers of each. The
      pronounced dependence of the dichroism on orientation of a tail grouping, itself
      remote from the localized initial C 1s site, indicates the presence of long range
      final state photoelectron scattering effects. Analogous data for the outermost
      valence orbital, partially localized on the carbonyl group, are also presented.
      The apparently enhanced sensitivity of the dichroism exhibited in this work is
      discussed in terms of the particular dependence on photoelectron interference
      effects that is probed by the dichroism measurement and is contrasted with the
      usual beta parameter and cross section determinations.

PMID- 17190558
TI  - Competitive bond breaking in floppy molecular trimers: HeNeH and HeNeH-
      calculations.
AB  - Calculations for the J=0 bound states associated with the two title molecular
      systems are carried out using distributed Gaussian function approach and using
      the sum of two-body potential approximation to describe the overall interactions.
      The results yield one bound state for the neutral trimer and three bound states
      for the anionic triatom. The relative values of dissociation energies place the
      first dissociation threshold at the H emission for the neutral complex and at the
      He emission for the corresponding anion. The general spatial properties of the
      various bound states are analyzed on both systems.

PMID- 17190559
TI  - n-alkanes on Pt(111) and on C(0001)Pt(111): chain length dependence of kinetic
      desorption parameters.
AB  - We have measured the desorption of seven small n-alkanes (C(N)H(2N+2), N=1
      4,6,8,10) from the Pt(111) and C(0001) surfaces by temperature programed
      desorption. We compare these results to our recent study of the desorption
      kinetics of these molecules on MgO(100) [J. Chem. Phys. 122, 164708 (2005)].
      There we showed an increase in the desorption preexponential factor by several
      orders of magnitude with increasing n-alkane chain length and a linear desorption
      energy scaling with a small y-intercept value. We suggest that the significant
      increase in desorption prefactor with chain length is not particular to the
      MgO(100) surface, but is a general effect for desorption of the small n-alkanes.
      This argument is supported by statistical mechanical arguments for the increase
      in the entropy gain of the molecules upon desorption. In this work, we
      demonstrate that this hypothesis holds true on both a metal surface and a
      graphite surface. We observe an increase in prefactor by five orders of magnitude
      over the range of n-alkane chain lengths studied here. On each surface, the
      desorption energies of the n-alkanes are found to increase linearly with the
      molecule chain length and have a small y-intercept value. Prior results of other
      groups have yielded a linear desorption energy scaling with chain length that has
      unphysically large y-intercept values. We demonstrate that by allowing the
      prefactor to increase according to our model, a reanalysis of their data resolves
      this y-intercept problem to some degree.

PMID- 17190560
TI  - Solvation and proton transfer in polar molecule nanoclusters.
AB  - Proton transfer in a phenol-amine complex dissolved in polar molecule
      nanoclusters is investigated. The proton transfer rates and mechanisms, as well
      as the solvation of the complex in the cluster, are studied using both adiabatic
      and nonadiabatic dynamics. The phenol-amine complex exists in ionic and covalent
      forms and as the size of the cluster increases the ionic form gains stability at
      the expense of the covalent form. Both the adiabatic and nonadiabatic transfer
      reaction rates increase with cluster size. Given a fixed cluster size, the
      stability of the covalent state increases with increasing temperature. The proton
      transfer rates do not change monotonously with an increase in temperature. A
      strong correlation between the solvent polarization reaction coordinate and the
      location of the phenol-amine complex in the cluster is found. The ionic form of
      the complex strongly prefers the interior of the cluster while the covalent form
      prefers to lie on the cluster surface.

PMID- 17190561
TI  - Time correlation function and finite field approaches to the calculation of the
      fifth order Raman response in liquid xenon.
AB  - The fifth order, two-dimensional Raman response in liquid xenon is calculated via
      a time correlation function (TCF) theory and the numerically exact finite field
      method. Both employ classical molecular dynamics simulations. The results are
      shown to be in excellent agreement, suggesting the efficacy of the TCF approach,
      in which the response function is written approximately in terms of a single
      classical multitime TCF.

PMID- 17190562
TI  - Hydrogen bond and residence dynamics of ion-water and water-water pairs in
      supercritical aqueous ionic solutions: dependence on ion size and density.
AB  - We have carried out a series of molecular dynamics simulations to investigate the
      hydrogen bond and residence dynamics of X(-)-water (X=F, Cl, and I) and pairs in
      aqueous solutions at a temperature of 673 K. The calculations are done at six
      different water densities ranging from 1.0 to 0.15 g cm(-3). The hydrogen bonds
      are defined by using a set of configurational criteria with respect to the
      anion(oxygen)-oxygen and anion(oxygen)-hydrogen distances and the anion(oxygen)
      oxygen-hydrogen angle for an anion(water)-water pair. The F(-)-water hydrogen
      bonds are found to have a longer lifetime than all other hydrogen bonds
      considered in the present study. The lifetime of Cl(-)-water hydrogen bonds is
      shorter than that of F(-)-water hydrogen bonds but longer than the lifetime of
      water-water hydrogen bonds. The lifetimes of I(-)-water and water-water hydrogen
      bonds are found to be very similar. Generally, the lifetimes of both anion-water
      and water-water hydrogen bonds are found to be significantly shorter than those
      found under ambient conditions. In addition to hydrogen bond lifetimes, we have
      also calculated the residence times and the orientational relaxation times of
      water molecules in ion(water) hydration shells and have discussed the
      correlations of these dynamical quantities with the observed dynamics of
      anion(water)-water hydrogen bonds as functions of the ion size and density of the
      supercritical solutions.

PMID- 17190563
TI  - Phase behavior of a symmetrical binary fluid mixture.
AB  - We have investigated the phase behavior of a symmetrical binary fluid mixture for
      the situation where the chemical potentials mu(1) and mu(2) of the two species
      differ. Attention is focused on the set of interparticle interaction strengths
      for which, when mu(1)=mu(2), the phase diagram exhibits both a liquid-vapor
      critical point and a tricritical point. The corresponding phase behavior for the
      case mu(1) not equalmu(2) is investigated via integral-equation theory
      calculations within the mean spherical approximation and grand canonical Monte
      Carlo (GCMC) simulations. We find that two possible subtypes of phase behavior
      can occur, these being distinguished by the relationship between the triple lines
      in the full phase diagram in the space of temperature, density, and
      concentration. We present the detailed form of the phase diagram for both
      subtypes and compare with the results from GCMC simulations, finding good overall
      agreement. The scenario via which one subtype evolves into the other is also
      studied, revealing interesting features.

PMID- 17190564
TI  - Spectra of the liquid cluster surface thermal fluctuations.
AB  - Classification of cluster particles is proposed that introduces three particle
      types: the internal particles, surface particles, and virtual chains of
      particles. Thermal fluctuations of a surface passing through the surface
      particles of a Lennard-Jones liquid cluster are studied using a molecular
      dynamics simulation. It is shown that for large clusters, the Fourier spectral
      amplitude of these fluctuations decays faster than 1q, where q is the wave
      number. The frequency Fourier spectrum shows an overdamped system behavior, which
      is the evidence for the absence of thermal capillary waves for clusters
      comprising less than 10(5) particles. The time-averaged cluster density profile
      is given by an error function with the width parameter diverging as the logarithm
      of the cluster size.

PMID- 17190565
TI  - Excited state properties and quadratic optical nonlinearities in charged organic
      chromophores: theoretical analysis.
AB  - As it has been found experimentally [K. Clays and B. Coe, Chem. Mater. 15, 642
      (2003); B. J. Coe et al., 126, 10418 (2004)], elongation of the conjugation path
      length and N-arylation in stilbazolium chromophores both lead to substantial
      enhancement of the molecular optical nonlinearities. In the present contribution
      the authors perform a quantum chemical analysis of the excited state properties
      and quadratic nonlinear optical responses of a series of this type of dyes.
      Nonlinear optical responses are estimated by both finite-field and two-state
      model approaches that demonstrate an excellent qualitative mutual agreement. Time
      dependent density functional theory calculations on the isolated cations predict
      redshift in the energy of the intramolecular charge transfer transition that is
      overestimated for cations with the longer conjugation path length. At the same
      time, in comparison with the Stark spectroscopy measurements the differences
      between the excited and ground state dipole moments are grossly underestimated
      for all compounds. The inclusion of solvent effect by polarizable continuum model
      affords a better agreement with experiment for these quantities. The authors'
      calculations demonstrate the crucial dependence of the electronic excitation
      properties on the way of the investigated compound geometry optimization. The
      origin of such dependence is discussed.

PMID- 17190566
TI  - The simulation of the three-dimensional lattice hydrophobic-polar protein
      folding.
AB  - One of the most prominent problems in computational biology is to predict the
      natural conformation of a protein from its amino acid sequence. This paper
      focuses on the three-dimensional hydrophobic-polar (HP) lattice model of this
      problem. The modified elastic net (EN) algorithm is applied to solve this
      nonlinear programming hard problem. The lattice partition strategy and two local
      search methods (LS(1) and LS(2)) are proposed to improve the performance of the
      modified EN algorithm. The computation and analysis of 12 HP standard benchmark
      instances are also involved in this paper. The results indicate that the hybrid
      of modified EN algorithm, lattice partition strategy, and local search methods
      has a greater tendency to form a globular state than genetic algorithm does. The
      results of noncompact model are more natural in comparison with that of compact
      model.

PMID- 17190567
TI  - Theoretical study of phosphorescence in dye doped light emitting diodes.
AB  - Phosphorescence of platinum(II) octaethyl porphyrin (PtOEP), which has been used
      in organic light emitting diodes to overcome the efficiency limit imposed by the
      formation of triplet excitons, is studied by time-dependent (TD) density
      functional theory (DFT). The spin-orbit coupling (SOC) effects and the
      phosphorescence radiative lifetime (tau(p) (r)), calculated by the TD DFT method
      with the quadratic response technique, are analyzed for a series of porphyrins in
      order to elucidate the internal heavy atom effect on tau(p) (r). While the
      significance of the d(pi) orbital admixture into the lowest unoccupied molecular
      orbital e(g)(pi(*)), proposed by Gouterman et al. [J. Chem. Phys. 56, 4073
      (1972)], is supported by our SOC calculations, we find that the charge-transfer
      (CT) mechanism is more important; the CT state of the (3)A(2g) symmetry provides
      effective SOC mixing with the ground state, and a large (3)A(2g)-(3)E(u)
      transition dipole moment gives the main contribution to the radiative
      phosphorescence rate constant. The IR and Raman spectra in the ground state and
      first excited triplet state (T(1)) are studied for proper assignment of vibronic
      patterns. An orbital angular momentum of the T(1) state is not quenched
      completely by the Jahn-Teller effect. A large zero-field splitting is predicted
      for PtP and PtOEP which results from a competition between the SOC and Jahn
      Teller effects. A strong vibronic activity is found for the e(g) mode at 230 cm(
      1) in PtP phosphorescence which is shifted to 260 cm(-1) in PtOEP. This out-of
      plane vibration of the Pt atom produces considerable change of the SOC mixing.
      The role of charge-transfer state of d(pi)pi(*) type is stressed for the
      explanation of the electroluminescent properties of the dye doped light emitting
      diode.

PMID- 17190568
TI  - Dielectric study of neutral and charged hydrogels during the swelling process.
AB  - Dielectric spectroscopy measurements of conductivity were applied for
      understanding the change in the internal morphology of the neutral and
      permanently charged polyacrylamide (PAAm) hydrogels during the swelling process.
      For the first time four distinct peaks (each corresponding to a different
      swelling stage) in the conductivity of the neutral gel were observed during the
      swelling of this gel. These peaks are related to the distribution of dense
      polymer regions (they are defined as the "blobs") appearing in a microstructure
      of the given PAAm gel having at least four average sizes. For the charged gel the
      heterogeneity decreases due to the internal electric field of the charged sites.
      Thus, this characteristic behavior in the conductivity becomes almost negligible
      for the gel charged with permanent SO(3) (-) groups. It seems this fact causes
      considerable decrease in amplitude of the peaks and overall decrease the
      conductivity during the whole swelling process especially at high frequencies.
      The new theory of dielectric relaxation based on the fractional kinetics
      containing the complex power-law exponents was used for verifying these swelling
      processes and received an excellent confirmation in description of the real part
      of the complex conductivity Re[sigma(omega)] by the fitting function that follows
      from the suggested theory. The calculated power-law exponents describe the
      behavior of Re[sigma(omega,mm(0))] in the available frequency range (30 Hz-13
      MHz) and for all values of the relative masses (volumes) measured in the process
      of the experiment. The excellent coincidence between the new theory and measured
      data gives a possibility to suggest more reliable physical picture of the
      swelling process that takes place in neutral/charged gels.

PMID- 17190569
TI  - Effects of chromophore orientation and molecule conformation on surface-enhanced
      Raman scattering studied with alkanoic acids and colloidal silver nanoparticles.
AB  - Experimental studies have been carried out to gain a better understanding of the
      effects of chromophore orientation and molecular conformation on surface-enhanced
      Raman scattering (SERS) based on metal nanostructures. A series of alkanoic acids
      that contain a phenyl ring separated by methylene groups from the carboxylic
      acid, including phenylacetic acid, 3-phenylpropionic acid, 4-phenylbutyric acid,
      5-phenylvaleric acid, and 6-phenylhexanoic acid, was investigated as model
      molecules with colloidal silver nanoparticles as SERS substrates. As the number
      of methylene groups increases, the molecules display an interesting zigzag
      intensity pattern of the phenyl ring bending mode around 1000 cm(-1) as well as a
      trend of appearance and disappearance of either the degenerate ring breathing
      mode or C[Double Bond]O vibrational mode near 1585 and 1630 cm(-1), respectively.
      Molecules containing an odd number of methylene units display a higher ring
      bending intensity and degenerate ring breathing mode and are suggested to have a
      trans conformation on the particle surface. Molecules with an even number of
      methylene units show a C[Double Bond]O vibrational mode and weaker ring bending
      in their SERS spectra and are suggested to have a gauche conformation on the
      silver nanoparticle surface. The different conformation is attributed to the
      varying interactions of the carboxylic group or the phenyl ring pi electrons with
      the silver surface. The SERS intensity was found to change little as the length
      between the phenyl ring and the carboxylic group was increased by adding CH(2)
      spacers. This is possibly because the effective distance between the phenyl ring
      and the silver surface does not change much with increasing number of CH(2)
      spacers as a result of changes in molecular conformation and variations in the
      phenyl ring orientation with CH(2) addition. The insight gained from this study
      is important for understanding SERS of complex molecules for which chromophore
      orientation and molecular conformation must be taken into careful consideration.

PMID- 17190570
TI  - Exciton recurrence motion in aggregate systems in the presence of quantized
      optical fields.
AB  - The exciton dynamics of model aggregate systems, dimer, trimer, and pentamer,
      composed of two-state monomers is computationally investigated in the presence of
      three types of quantized optical fields, i.e., coherent, amplitude-squeezed, and
      phase-squeezed fields, in comparison with the case of classical laser fields. The
      constituent monomers are assumed to interact with each other by the dipole-dipole
      interaction, and the two-exciton model, which takes into account both the one-
      and two-exciton generations, is employed. As shown in previous studies, near
      degenerate exciton states in the presence of a (near) resonant classical laser
      field create quantum superposition states and thus cause the spatial exciton
      recurrence motion after cutting the applied field. In contrast, continuously
      applied quantized optical fields turn out to induce similar exciton recurrence
      motions in the quiescent region between the collapse and revival behaviors of
      Rabi oscillation. The spatial features of exciton recurrence motions are shown to
      depend on the architecture of aggregates. It is also found that the coherent and
      amplitude-squeezed fields tend to induce longer-term exciton recurrence behavior
      than the phase-squeezed field. These features have a possibility for opening up a
      novel creation and control scheme of exciton recurrence motions in aggregate
      systems under the quantized optical fields.

PMID- 17190571
TI  - Heterogeneous dynamics, ageing, and rejuvenating in van der Waals liquids.
AB  - It has been shown over the past ten years that the dynamics close to the glass
      transition is strongly heterogeneous: fast domains coexist with domains three or
      four decades slower, the size of these regions being about 3 nm at T(g). The
      authors extend here a model that has been proposed recently for the glass
      transition in van der Waals liquids. The authors describe in more details the
      mechanisms of the alpha relaxation in such liquids. It allows then to interpret
      physical ageing in van der Waals liquids as the evolution of the density
      fluctuation distribution towards the equilibrium one. The authors derive the
      expression of macroscopic quantities (volume, compliance, etc.). Numerical
      results are compared with experimental data (shape, times to reach equilibrium)
      for simple thermal histories (quenches, annealings). The authors explain the
      existence of a "Kovacs memory effect" and the temporal asymmetry between down
      jump and up jump temperatures experiments, even for systems for which there is no
      energy barriers. Their model allows also for calculating the evolution of small
      probe diffusion coefficients during ageing.

PMID- 17190572
TI  - Analytical coarse-grained description for polymer melts.
AB  - Starting from the Ornstein-Zernike equation the authors derive an analytical
      theory, at the level of pair correlation functions, which coarse grains polymer
      melts into liquids of interacting soft colloidal particles. Since it is
      analytical, the presented coarse-graining approach will be useful in developing
      multiscale modeling procedures to simulate complex fluids of macromolecules. The
      accuracy of the theory is tested by its capacity to reproduce the liquid
      structure, as given by the center-of-mass intermolecular total pair correlation
      function. The theory is found to agree well with the structure predicted by
      molecular dynamics simulations of the liquid described at the united atom level
      as well as by molecular dynamics simulations of the liquid of interacting
      colloidal particles. The authors perform simulations of the liquid of interacting
      colloidal particles having as input the potential obtained from their analytical
      total pair correlation function by enforcing the hypernetted-chain closure
      approximation. Tests systems are polyethylene melts of chains with increasing
      degrees of polymerization and polymer melts of chains with different chemical
      architectures. They also discuss the effect of adopting different conventional
      approximations for intra- and intermolecular monomer structure factors on the
      accuracy of the coarse-graining procedure, as well as the relevance of higher
      order corrections to their expression.

PMID- 17190573
TI  - Exploring DNA groove water dynamics through hydrogen bond lifetime and
      orientational relaxation.
AB  - Dynamics of water molecules in the grooves of DNA are of great interest both for
      practical (functionality of DNA) and fundamental (as examples of confined
      systems) interest. Here the authors employ atomistic molecular dynamics
      simulations to understand varying water dynamics at the minor and the major
      grooves of a 38 base-pair long DNA duplex in water. In order to understand and
      quantify the diversity in the nature of hydrogen bond due to many hydrogen bond
      donors and acceptors present in the four bases, they have undertaken study of
      hydrogen bond lifetime (HBLT) correlation functions of all the specific hydrogen
      bonds between the base atoms and water molecules. They find that the HBLT
      correlation functions are in general multiexponential, with the average lifetime
      depending significantly on the specificity and may thus be biologically relevant.
      The average hydrogen bond lifetime is longer in the minor groove than that in the
      major groove by almost a factor of 2. Analysis further shows that water hydrogen
      bonds with phosphate oxygen have substantially shorter lifetimes than those with
      the groove atoms. They also compute two different orientational time correlation
      functions (OTCFs) of the water molecules present at the major and the minor
      grooves and attempt to correlate OTCF with HBLT correlation function. The OTCFs
      in the minor groove exhibit three time scales, with the time constant of the
      slowest component one to two orders of magnitude longer than what is observed for
      bulk water. A slow component is also present for the major groove water but with
      shorter time constant. Interestingly, correlation between reformations allowed
      HBLT correlation function [C(HB)(t)] and the OTCF markedly deviates from each
      other in the grooves, indicating enhanced rigidity of water molecules in the
      grooves.

PMID- 17190574
TI  - Anomalous small angle x-ray scattering determination of ion distribution around a
      polyelectrolyte biopolymer in salt solution.
AB  - The distribution of counterions in solutions of high molecular mass hyaluronic
      acid, in near-physiological conditions where mono- and divalent ions are
      simultaneously present, is studied by small angle neutron scattering and
      anomalous small angle x-ray scattering. The solutions contain either sodium or
      rubidium chloride together with varying concentrations of calcium or strontium
      chloride. The effects of monovalent-divalent ion exchange dominate the amplitude
      and the form of the counterion cloud. In the absence of divalent ions, the shape
      of the anomalous scattering signal from the monovalent ions is consistent with
      the distribution calculated from the Poisson-Boltzmann equation, as found by
      other workers. In mixtures of monovalent and divalent ions, however, as the
      divalent ion concentration increases, both the diameter and the amplitude of the
      monovalent ion cloud decrease. The divalent counterions always occupy the
      immediate neighborhood of the charged polyanion. Above a given concentration
      their anomalous scattering signal saturates. Even in a large excess of divalent
      ions, ion exchange is incomplete.

PMID- 17190575
TI  - Simulations of the dynamics of thermal undulations in lipid bilayers in the
      tensionless state and under stress.
AB  - The relaxation processes of height undulations and density fluctuations in a
      membrane have been studied by molecular dynamics simulations of a coarse grained
      amphiphilic bilayer model. We observe a double exponential decay in their time
      correlations, with relaxation rates in good quantitative agreement with the
      theory by Seifert and Langer [Europhys. Lett. 23, 71 (1993)]. Intermonolayer
      friction due to slippage between the two monolayers is shown to be the dominant
      dissipative mechanism at the high wave numbers, q>10 mum(-1), typically
      encountered in computer simulations. We briefly discuss the ramifications of the
      slow undulatory relaxation process for the calculation of bending rigidities from
      the static undulation structure factors. The relaxation rates are sensitive to
      the surface tension, and at high elongations an oscillatory contribution is
      observed in the time correlation of the undulations.

PMID- 17190576
TI  - Driving forces behind ion-ion correlations.

PMID- 17190577
TI  - Role of effective atomic masses in memory function-based models for liquids: a
      simulation study of liquid water.

PMID- 17190587
TI  - Non-randomised patients in a cholecystectomy trial: characteristics, procedures,
      and outcomes.
AB  - BACKGROUND: Laparoscopic cholecystectomy is now considered the first option for
      gallbladder surgery. However, 20% to 30% of cholecystectomies are completed as
      open operations often on elderly and fragile patients. The external validity of
      randomised trials comparing mini-laparotomy cholecystectomy and laparoscopic
      cholecystectomy has not been studied. The aim of this study is to analyse
      characteristics, procedures, and outcomes for all patients who underwent
      cholecystectomy without being included in such a trial. METHODS: Characteristics
      (age, sex, co-morbidity, and ASA-score), operation time, hospital stay, and
      mortality were compared for patients who underwent cholecystectomy outside and
      within a randomised controlled trial comparing mini-laparotomy and laparoscopic
      cholecystectomy. RESULTS: During the inclusion period 1719 patients underwent
      cholecystectomy. 726 patients were randomised and 724 of them completed the
      trial; 993 patients underwent cholecystectomy outside the trial. The non
      randomised patients were older--and had more complications from gallstone
      disease, higher co-morbidity, and higher ASA--score when compared with trial
      patients. They were also more likely to undergo acute surgery and they had a
      longer postoperative hospital stay, with a median 3 versus 2 days (p < 0.001 for
      all comparisons). Standardised mortality ratio within 90 days of operation was
      3.42 (mean) (95% CI 2.17 to 5.13) for non-randomised patients and 1.61 (mean)
      (95%CI 0.02 to 3.46) for trial patients. For non-randomised patients, operation
      time did not differ significantly between mini-laparotomy and open
      cholecystectomy in multivariate analysis. However, the operation for laparoscopic
      cholecystectomy lasted 20 minutes longer than open cholecystectomy. Hospital stay
      was significantly shorter for both mini-laparotomy and laparoscopic
      cholecystectomy compared to open cholecystectomy. CONCLUSION: Non-randomised
      patients were older and more sick than trial patients. The assignment of
      healthier patients to trials comparing mini-laparotomy cholecystectomy and
      laparoscopic cholecystectomy limits the external validity of conclusions reached
      in such trials.

PMID- 17190588
TI  - Collagen reorganization at the tumor-stromal interface facilitates local
      invasion.
AB  - BACKGROUND: Stromal-epithelial interactions are of particular significance in
      breast tissue as misregulation of these interactions can promote tumorigenesis
      and invasion. Moreover, collagen-dense breast tissue increases the risk of breast
      carcinoma, although the relationship between collagen density and tumorigenesis
      is not well understood. As little is known about epithelial-stromal interactions
      in vivo, it is necessary to visualize the stroma surrounding normal epithelium
      and mammary tumors in intact tissues to better understand how matrix
      organization, density, and composition affect tumor formation and progression.
      METHODS: Epithelial-stromal interactions in normal mammary glands, mammary
      tumors, and tumor explants in three-dimensional culture were studied with
      histology, electron microscopy, and nonlinear optical imaging methodologies.
      Imaging of the tumor-stromal interface in live tumor tissue ex vivo was performed
      with multiphoton laser-scanning microscopy (MPLSM) to generate multiphoton
      excitation (MPE) of endogenous fluorophores and second harmonic generation (SHG)
      to image stromal collagen. RESULTS: We used both laser-scanning multiphoton and
      second harmonic generation microscopy to determine the organization of specific
      collagen structures around ducts and tumors in intact, unfixed and unsectioned
      mammary glands. Local alterations in collagen density were clearly seen, allowing
      us to obtain three-dimensional information regarding the organization of the
      mammary stroma, such as radiating collagen fibers that could not have been
      obtained using classical histological techniques. Moreover, we observed and
      defined three tumor-associated collagen signatures (TACS) that provide novel
      markers to locate and characterize tumors. In particular, local cell invasion was
      found predominantly to be oriented along certain aligned collagen fibers,
      suggesting that radial alignment of collagen fibers relative to tumors
      facilitates invasion. Consistent with this observation, primary tumor explants
      cultured in a randomly organized collagen matrix realigned the collagen fibers,
      allowing individual tumor cells to migrate out along radially aligned fibers.
      CONCLUSION: The presentation of these tumor-associated collagen signatures
      allowed us to identify pre-palpable tumors and see cells at the tumor-stromal
      boundary invading into the stroma along radially aligned collagen fibers. As
      such, TACS should provide indications that a tumor is, or could become, invasive,
      and may serve as part of a strategy to help identify and characterize breast
      tumors in animal and human tissues.

PMID- 17190590
TI  - Effects of increased intracellular Cl- concentration on membrane responses to
      acetylcholine in the isolated endothelium of guinea pig mesenteric arteries.
AB  - ACh-induced membrane responses in vascular endothelial cells that have been
      reported vary between preparations from a sustained hyperpolarization to a
      transient hyperpolarization followed by a depolarization; the reason for this
      variation is unknown. Using the perforated whole-cell clamp technique, we
      investigated ACh-induced membrane currents in freshly isolated endothelial layers
      having a resting membrane potential of less negative than -10 mV. A group of
      cells was electrically isolated using a wide-bore micropipette, and their
      membrane potential was well controlled. ACh activated K(+) and Cl(-) currents
      simultaneously. The K(+) current was blocked by a combination of charybdotoxin
      and apamin and appears to result from the opening of IK(Ca) and SK(Ca) channels.
      The Cl(-) current was partially blocked by tamoxifen, niflumic acid, or DIDS and
      appears to be produced by Ca(2+)-activated Cl(-) channels. When the pipettes
      contained 20 mM Cl(-), the ACh-induced K(+) conductance started decreasing during
      a 1-min application of ACh while the Cl(-) conductance continued, making the ACh
      induced hyperpolarization sustained. When the pipettes contained 150 mM Cl(-),
      both conductances started decreasing during a 1-min application of ACh, making
      the ACh-induced hyperpolarization small and transient. [Cl(-)](i) is very likely
      modified by experimental procedures such as the cell isolation and the
      intracellular dialysis with the pipette solution. Such a variability in [Cl(
      )](i) may be one of the reasons for the variations in the ACh-induced membrane
      response.

PMID- 17190591
TI  - Discovering the RNA double helix and hybridization.
AB  - The discovery, 50 years ago, that RNA could form a double helix made possible a
      number of advances, including an understanding that led, decades later, to the
      discovery of microRNAs and RNA interference. Remarkably, the first nucleic acid
      hybridization reaction was also described in the same report.

PMID- 17190589
TI  - The childbearing health and related service needs of newcomers (CHARSNN) study
      protocol.
AB  - BACKGROUND: Refugee and asylum-seeking women in Canada may have significant
      harmful childbearing health outcomes and unmet health and social care needs. The
      most vulnerable of these women are: those who have left their countries by force
      (e.g., war, rape or abuse histories), are separated from their families, have
      limited knowledge of the host country languages, and are visible minorities.
      Asylum-seekers face additional stresses related to their unknown future status
      and are marginalized with regards to access to provincial health care systems.
      The prevalence and severity of health issues in this population is not known nor
      is the extent of response from social service and health care systems (including
      variation in provincial service delivery). Understanding the magnitude of health
      and social concerns of newcomers requires data from a representative sample of
      childbearing refugee and asylum-seeking women resettling in Canada to permit
      comparisons to be made with non-refugee immigrant and Canadian-born women. Our
      research questions are: (1) Do refugee or asylum-seeking women and their infants,
      experience a greater number or a different distribution of harmful health events
      during pregnancy, at birth, and during the postpartum period than non-refugee
      immigrant or Canadian-born women? (2) Are the harmful health events experienced
      postpartum by asylum-seeking women and their infants, addressed less often
      (compared to refugees, non-refugee immigrants, and Canadian-born women) by the
      Canadian health care system as delivered in each of the three major receiving
      cities for newcomers? METHODS/DESIGN: This is a four-year multi-site prospective
      cohort study (pregnancy to 4 months postpartum). We will seek to recruit 2400
      women [200 in each of 4 groups (refugees, asylum-seekers, non-refugee immigrants,
      and Canadian-born) from 1 of 12 postpartum hospital units across the 3 largest
      receiving cities for newcomers to Canada - Montreal, Toronto, and Vancouver].
      DISCUSSION: Knowledge of the extent of harmful health events occurring to asylum
      seeking, refugee, immigrant, and Canadian-born women, and the response of the
      health care system to those events and group differences, if they exist, will
      inform immigration and health policy makers as well as providers of services.

PMID- 17190592
TI  - Hosting neurotoxicity in polyglutamine disease.
AB  - Polyglutamine diseases are caused by an expanded glutamine domain thought to
      confer a toxic activity onto the respective disease proteins. In this issue,
      propose that toxicity of the polyglutamine protein Ataxin-1 may not be due to
      abberant protein interactions mediated by the polyglutamine expansion. Instead,
      they suggest that toxicity is solely due to interactions of Ataxin-1 with its
      normal binding partners.

PMID- 17190594
TI  - A molecular "zipper" for microtubules.
AB  - The dynamics of the microtubule cytoskeleton are controlled by microtubule
      associated proteins (MAPs). In this issue, show that Mal3p, the yeast EB1
      homolog, belongs to a new class of MAPs that "zipper" up the seam of the
      microtubule lattice.

PMID- 17190593
TI  - Keeping the noise down in ES cells.
AB  - A new report (Szutorisz et al., 2006) suggests that embryonic stem (ES) cells
      adopt an unusual strategy to remain perpetually poised for differentiation.
      Apparently, ES cells use the proteasome to target transcriptional preinitiation
      complexes, thus minimizing transcriptional noise at genes that promote
      differentiation.

PMID- 17190595
TI  - Treating muscular dystrophy with stem cells?
AB  - There is currently no effective treatment for the devastating muscle-wasting
      disease Duchenne muscular dystrophy (DMD). Cossu and colleagues report in a
      recent Nature paper that transplantation of mesoangioblast stem cells may hold
      promise for treating DMD. Further studies are required to fully evaluate the
      clinical potential of these blood-vessel-associated stem cells.

PMID- 17190596
TI  - Retrograde control of neural circuit formation.
AB  - Glial-derived neurotrophic factor (GDNF), secreted by skeletal muscle, triggers
      expression of the ETS transcription factor Pea3 in a subset of motor neurons in
      the spinal cord. In this issue, find that this retrograde GDNF-Pea3 signal
      controls dendrite patterning and assembly of a sensory-motor reflex circuit.

PMID- 17190597
TI  - The molecular genetics of crop domestication.
AB  - Ten thousand years ago human societies around the globe began to transition from
      hunting and gathering to agriculture. By 4000 years ago, ancient peoples had
      completed the domestication of all major crop species upon which human survival
      is dependent, including rice, wheat, and maize. Recent research has begun to
      reveal the genes responsible for this agricultural revolution. The list of genes
      to date tentatively suggests that diverse plant developmental pathways were the
      targets of Neolithic "genetic tinkering," and we are now closer to understanding
      how plant development was redirected to meet the needs of a hungry world.

PMID- 17190598
TI  - ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1
      neuropathology.
AB  - Spinocerebellar ataxia type 1 (SCA1) is one of several neurodegenerative diseases
      caused by expansion of a polyglutamine tract in the disease protein, in this
      case, ATAXIN-1 (ATXN1). A key question in the field is whether neurotoxicity is
      mediated by aberrant, novel interactions with the expanded protein or whether its
      wild-type functions are augmented to a deleterious degree. We examined soluble
      protein complexes from mouse cerebellum and found that the majority of wild-type
      and expanded ATXN1 assembles into large stable complexes containing the
      transcriptional repressor Capicua. ATXN1 directly binds Capicua and modulates
      Capicua repressor activity in Drosophila and mammalian cells, and its loss
      decreases the steady-state level of Capicua. Interestingly, the S776A mutation,
      which abrogates the neurotoxicity of expanded ATXN1, substantially reduces the
      association of mutant ATXN1 with Capicua in vivo. These data provide insight into
      the function of ATXN1 and suggest that SCA1 neuropathology depends on native, not
      novel, protein interactions.

PMID- 17190599
TI  - UvrD helicase unwinds DNA one base pair at a time by a two-part power stroke.
AB  - Helicases use the energy derived from nucleoside triphosphate hydrolysis to
      unwind double helices in essentially every metabolic pathway involving nucleic
      acids. Earlier crystal structures have suggested that DNA helicases translocate
      along a single-stranded DNA in an inchworm fashion. We report here a series of
      crystal structures of the UvrD helicase complexed with DNA and ATP hydrolysis
      intermediates. These structures reveal that ATP binding alone leads to unwinding
      of 1 base pair by directional rotation and translation of the DNA duplex, and ADP
      and Pi release leads to translocation of the developing single strand. Thus DNA
      unwinding is achieved by a two-part power stroke in a combined wrench-and
      inchworm mechanism. The rotational angle and translational distance of DNA define
      the unwinding step to be 1 base pair per ATP hydrolyzed. Finally, a gateway for
      ssDNA translocation and an alternative strand-displacement mode may explain the
      varying step sizes reported previously.

PMID- 17190601
TI  - The proteasome restricts permissive transcription at tissue-specific gene loci in
      embryonic stem cells.
AB  - The ability of stem cells to activate different gene expression programs requires
      the choreographed assembly of trans-acting factors at enhancers and promoters
      during cell differentiation. In this study, we show that the proteasome acts on
      specific regulatory regions in embryonic stem (ES) cells to prevent incorrect
      transcriptional initiation. Chemical or siRNA-mediated inhibition of proteasome
      activity results in increased transcription factor and RNA polymerase II binding
      and leads to activation of cryptic promoters. Analysis of the binding profiles of
      different proteasome subunits in normal ES cells and following RNAi knockdown of
      individual subunits provides evidence for a targeted assembly of the 26S
      proteasome at specific regulatory elements. Our results suggest that the
      proteasome promotes a dynamic turnover of transcription factor and Pol II binding
      at tissue-specific gene domains in ES cells, thereby restricting permissive
      transcriptional activity and keeping the genes in a potentiated state, ready for
      activation at later stages.

PMID- 17190600
TI  - Structural basis for the methylation state-specific recognition of histone H4-K20
      by 53BP1 and Crb2 in DNA repair.
AB  - Histone lysine methylation has been linked to the recruitment of mammalian DNA
      repair factor 53BP1 and putative fission yeast homolog Crb2 to DNA double-strand
      breaks (DSBs), but how histone recognition is achieved has not been established.
      Here we demonstrate that this link occurs through direct binding of 53BP1 and
      Crb2 to histone H4. Using X-ray crystallography and nuclear magnetic resonance
      (NMR) spectroscopy, we show that, despite low amino acid sequence conservation,
      both 53BP1 and Crb2 contain tandem tudor domains that interact with histone H4
      specifically dimethylated at Lys20 (H4-K20me2). The structure of 53BP1/H4-K20me2
      complex uncovers a unique five-residue 53BP1 binding cage, remarkably conserved
      in the structure of Crb2, that best accommodates a dimethyllysine but excludes a
      trimethyllysine, thus explaining the methylation state-specific recognition of H4
      K20. This study reveals an evolutionarily conserved molecular mechanism of
      targeting DNA repair proteins to DSBs by direct recognition of H4-K20me2.

PMID- 17190602
TI  - Human mRNA export machinery recruited to the 5' end of mRNA.
AB  - Pre-mRNAs undergo splicing to remove introns, and the spliced mRNA is exported to
      the cytoplasm for translation. Here we investigated the mechanism for recruitment
      of the conserved mRNA export machinery (TREX complex) to mRNA. We show that the
      human TREX complex is recruited to a region near the 5' end of mRNA, with the
      TREX component Aly bound closest to the 5' cap. Both TREX recruitment and mRNA
      export require the cap, and these roles for the cap are splicing dependent.
      CBP80, which is bound to the cap, associates efficiently with TREX, and Aly
      mediates this interaction. Together, these data indicate that the CBP80-Aly
      interaction results in recruitment of TREX to the 5' end of mRNA, where it
      functions in mRNA export. As a consequence, the mRNA would be exported in a 5' to
      3' direction through the nuclear pore, as observed in early electron micrographs
      of giant Balbiani ring mRNPs.

PMID- 17190603
TI  - Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and
      deubiquitinating activities.
AB  - The ubiquitin ligase Hul5 was recently identified as a component of the
      proteasome, a multisubunit protease that degrades ubiquitin-protein conjugates.
      We report here a proteasome-dependent conjugating activity of Hul5 that endows
      proteasomes with the capacity to extend ubiquitin chains. hul5 mutants show
      reduced degradation of multiple proteasome substrates in vivo, suggesting that
      the polyubiquitin signal that targets substrates to the proteasome can be
      productively amplified at the proteasome. However, the products of Hul5
      conjugation are subject to disassembly by a proteasome-bound deubiquitinating
      enzyme, Ubp6. A hul5 null mutation suppresses a ubp6 null mutation, suggesting
      that a balance of chain-extending and chain-trimming activities is required for
      proper proteasome function. As the association of Hul5 with proteasomes was found
      to be strongly stabilized by Ubp6, these enzymes may be situated in proximity to
      one another. We propose that through dynamic remodeling of ubiquitin chains,
      proteasomes actively regulate substrate commitment to degradation.

PMID- 17190604
TI  - The Schizosaccharomyces pombe EB1 homolog Mal3p binds and stabilizes the
      microtubule lattice seam.
AB  - End binding 1 (EB1) proteins are highly conserved regulators of microtubule
      dynamics. Using electron microscopy (EM) and high-resolution surface shadowing we
      have studied the microtubule-binding properties of the fission yeast EB1 homolog
      Mal3p. This allowed for a direct visualization of Mal3p bound on the surface of
      microtubules. Mal3p particles usually formed a single line on each microtubule
      along just one of the multiple grooves that are formed by adjacent
      protofilaments. We provide structural data showing that the alignment of Mal3p
      molecules coincides with the microtubule lattice seam as well as data suggesting
      that Mal3p not only binds but also stabilizes this seam. Accordingly, Mal3p
      stabilizes microtubules through a specific interaction with what is potentially
      the weakest part of the microtubule in a way not previously demonstrated. Our
      findings further suggest that microtubules exhibit two distinct reaction
      platforms on their surface that can independently interact with target structures
      such as microtubule-associated proteins, motors, kinetochores, or membranes.

PMID- 17190605
TI  - Dual detection of fungal infections in Drosophila via recognition of glucans and
      sensing of virulence factors.
AB  - The Drosophila immune system discriminates between various types of infections
      and activates appropriate signal transduction pathways to combat the invading
      microorganisms. The Toll pathway is required for the host response against fungal
      and most Gram-positive bacterial infections. The sensing of Gram-positive
      bacteria is mediated by the pattern recognition receptors PGRP-SA and GNBP1 that
      cooperate to detect the presence of infections in the host. Here, we report that
      GNBP3 is a pattern recognition receptor that is required for the detection of
      fungal cell wall components. Strikingly, we find that there is a second, parallel
      pathway acting jointly with GNBP3. The Drosophila Persephone protease activates
      the Toll pathway when proteolytically matured by the secreted fungal virulence
      factor PR1. Thus, the detection of fungal infections in Drosophila relies both on
      the recognition of invariant microbial patterns and on monitoring the effects of
      virulence factors on the host.

PMID- 17190606
TI  - Target-induced transcriptional control of dendritic patterning and connectivity
      in motor neurons by the ETS gene Pea3.
AB  - The apposition of axon terminals and dendrites is critical for the control of
      neuronal activation, but how distinct neuronal subpopulations establish selective
      dendrite patterns and acquire specific presynaptic inputs remains unclear. Spinal
      motor neuron (MN) pools project to specific target muscles and are activated by
      selective synaptic inputs from group Ia proprioceptive afferents (IaPAs). Here,
      we show that MN pools with radially projecting dendrites respond to sensory
      stimulation with monosynaptic latency and are strikingly different from MN pools
      with dendrites that avoid the central gray matter, which are only activated
      through indirect connections. We provide genetic evidence that the induction of
      the ETS transcription factor Pea3 by GDNF is essential in two cervical MN pools
      to control dendrite patterning and selectivity of IaPA connectivity. These
      findings suggest that target-induced transcriptional programs control MN dendrite
      orientation and play a crucial role in the establishment of sensory-motor
      connections in the spinal cord.

PMID- 17190609
TI  - Beta-structures in fibrous proteins.
AB  - The beta-form of protein folding, one of the earliest protein structures to be
      defined, was originally observed in studies of silks. It was then seen in early
      studies of synthetic polypeptides and, of course, is now known to be present in a
      variety of guises as an essential component of globular protein structures.
      However, in the last decade or so it has become clear that the beta-conformation
      of chains is present not only in many of the amyloid structures associated with,
      for example, Alzheimer's Disease, but also in the prion structures associated
      with the spongiform encephalopathies. Furthermore, X-ray crystallography studies
      have revealed the high incidence of the beta-fibrous proteins among virulence
      factors of pathogenic bacteria and viruses. Here we describe the basic forms of
      the beta-fold, summarize the many different new forms of beta-structural fibrous
      arrangements that have been discovered, and review advances in structural studies
      of amyloid and prion fibrils. These and other issues are described in detail in
      later chapters.

PMID- 17190607
TI  - Neuronal transcriptome of Aplysia: neuronal compartments and circuitry.
AB  - Molecular analyses of Aplysia, a well-established model organism for cellular and
      systems neural science, have been seriously handicapped by a lack of adequate
      genomic information. By sequencing cDNA libraries from the central nervous system
      (CNS), we have identified over 175,000 expressed sequence tags (ESTs), of which
      19,814 are unique neuronal gene products and represent 50%-70% of the total
      Aplysia neuronal transcriptome. We have characterized the transcriptome at three
      levels: (1) the central nervous system, (2) the elementary components of a simple
      behavior: the gill-withdrawal reflex-by analyzing sensory, motor, and
      serotonergic modulatory neurons, and (3) processes of individual neurons. In
      addition to increasing the amount of available gene sequences of Aplysia by two
      orders of magnitude, this collection represents the largest database available
      for any member of the Lophotrochozoa and therefore provides additional insights
      into evolutionary strategies used by this highly successful diversified lineage,
      one of the three proposed superclades of bilateral animals.

PMID- 17190608
TI  - Spatial and temporal properties of the illusory motion-induced position shift for
      drifting stimuli.
AB  - The perceived position of a stationary Gaussian window of a Gabor target shifts
      in the direction of motion of the Gabor's carrier stimulus, implying the presence
      of interactions between the specialized visual areas that encode form, position,
      and motion. The purpose of this study was to examine the temporal and spatial
      properties of this illusory motion-induced position shift (MIPS). We measured the
      magnitude of the MIPS for a pair of horizontally separated (2 or 8deg) truncated
      Gabor stimuli (carrier=1 or 4cpd sinusoidal grating, Gaussian envelope SD=18arc
      min, 50% contrast) or a pair of Gaussian-windowed random-texture patterns that
      drifted vertically in opposite directions. The magnitude of the MIPS was measured
      for drift speeds up to 16deg/s and for stimulus durations up to 453ms. The
      temporal properties of the MIPS depended on the drift speed. At low velocities,
      the magnitude of the MIPS increased monotonically with the stimulus duration. At
      higher velocities, the magnitude of the MIPS increased with duration initially,
      then decreased between approximately 45 and 75ms before rising to reach a steady
      state value at longer durations. In general, the magnitude of the MIPS was larger
      when the truncated-Gabor or random-texture stimuli were more spatially separated,
      but was similar for the different types of carrier stimuli. Our results are
      consistent with a framework that suggests that perceived form is modulated
      dynamically during stimulus motion.

PMID- 17190610
TI  - Beta-silks: enhancing and controlling aggregation.
AB  - It appears that fiber-forming proteins are not an exclusive group but that, with
      appropriate conditions, many proteins can potentially aggregate and form fibrils;
      though only certain proteins, for example, amyloids and silks, do so under normal
      physiological conditions. Even so, this suggests a ubiquitous aggregation
      mechanism in which the protein environment is at least as important as the
      sequence. An ideal model system in which forced and natural aggregation has been
      observed is silk. Silks have evolved specifically to readily form insoluble
      ordered structures with a wide range of structural functionality. The animal, be
      it silkworm or spider, will produce, store, and transport high molecular weight
      proteins in a complex environment to eventually allow formation of silk fibers
      with a variety of mechanical properties. Here we review fiber formation and its
      prerequisites, and discuss the mechanism by which the animal facilitates and
      modulates silk assembly to achieve controlled protein aggregation.

PMID- 17190611
TI  - Beta-rolls, beta-helices, and other beta-solenoid proteins.
AB  - Beta-rolls and beta-helices belong to a larger group of topologically similar
      proteins with solenoid folds: because their regular secondary structure elements
      are exclusively beta-strands, they are referred to as beta-solenoids. The number
      of beta-solenoids whose structures are known is now large enough to support a
      systematic analysis. Here we survey the distinguishing structural features of
      beta-solenoids, also documenting their notable diversity. Appraisal of these
      structures suggests a classification based on handedness, twist, oligomerization
      state, and coil shape. In addition, beta-solenoids are distinguished by the
      number of chains that wind around a common axis: the majority are single-stranded
      but there is a recently discovered subset of triple-stranded beta-solenoids. This
      survey has revealed some relationships of the amino acid sequences of beta
      solenoids with their structures and functions-in particular, the repetitive
      character of the coil sequences and conformations that recur in tracts of tandem
      repeats. We have proposed the term beta-arc for the distinctive turns found in
      beta-solenoids and beta-arch for the corresponding strand-turn-strand motifs. The
      evolutionary mechanisms underlying these proteins are also discussed. This
      analysis has direct implications for sequence-based detection, structural
      prediction, and de novo design of other beta-solenoid proteins. The abundance of
      virulence factors, toxins and allergens among beta-solenoids, as well as
      commonalities of beta-solenoids with amyloid fibrils, imply that this class of
      folds may have a broader role in human diseases than was previously recognized.
      Thus, identification of genes with putative beta-solenoid domains promises to be
      a fertile direction in the search for viable targets in the development of new
      antibiotics and vaccines.

PMID- 17190612
TI  - Natural triple beta-stranded fibrous folds.
AB  - A distinctive family of beta-structured folds has recently been described for
      fibrous proteins from viruses. Virus fibers are usually involved in specific host
      cell recognition. They are asymmetric homotrimeric proteins consisting of an N
      terminal virus-binding tail, a central shaft or stalk domain, and a C-terminal
      globular receptor-binding domain. Often they are entirely or nearly entirely
      composed of beta-structure. Apart from their biological relevance and possible
      gene therapy applications, their shape, stability, and rigidity suggest they may
      be useful as blueprints for biomechanical design. Folding and unfolding studies
      suggest their globular C-terminal domain may fold first, followed by a "zipping
      up" of the shaft domains. The C-terminal domains appear to be important for
      registration because peptides corresponding to shaft domains alone aggregate into
      nonnative fibers and/or amyloid structures. C-terminal domains can be exchanged
      between different fibers and the resulting chimeric proteins are useful as a way
      to solve structures of unknown parts of the shaft domains. The following natural
      triple beta-stranded fibrous folds have been discovered by X-ray crystallography:
      the triple beta-spiral, triple beta-helix, and T4 short tail fiber fold. All have
      a central longitudinal hydrophobic core and extensive intermonomer polar and
      nonpolar interactions. Now that a reasonable body of structural and folding
      knowledge has been assembled about these fibrous proteins, the next challenge and
      opportunity is to start using this information in medical and industrial
      applications such as gene therapy and nanotechnology.

PMID- 17190614
TI  - X-Ray fiber and powder diffraction of PrP prion peptides.
AB  - A conformational change from the alpha-helical, cellular form of prion to the
      beta-sheet, scrapie (infectious) form is the central event for prion replication.
      The folding mechanism underlying this conformational change has not yet been
      deciphered. Here, we review prion pathology and summarize X-ray fiber and powder
      diffraction studies on the N-terminal fragments of prion protein and on short
      sequences that initiate the beta-assembly for various fibrils, including poly(L
      alanine) and poly(L-glutamine). We discuss how the quarter-staggered beta-sheet
      assembly (like in polyalanine) and polar-zipper beta-sheet formation (like in
      polyglutamine) may be involved in the formation of the scrapie form of prion.

PMID- 17190613
TI  - Structure, function, and amyloidogenesis of fungal prions: filament polymorphism
      and prion variants.
AB  - Infectious proteins (prions) became an important medical issue when they were
      identified as agents of the transmissible spongiform encephalopathies. More
      recently, prions have been found in fungi and their investigation has been
      facilitated by greater experimental tractability. In each case, the normal form
      of the prion protein may be converted into the infectious form (the prion itself)
      in an autocatalytic process; conversion may either occur spontaneously or by
      transmission from an already infected cell. Four fungal prion proteins have been
      studied in some depth-Ure2p, Sup35p, and Rnq1p of Saccharomyces cerevisiae and
      HET-s of Podospora anserina. Each has a "prion domain" that governs infectivity
      and a "functional domain" that contributes the protein's activity in a wild-type
      cell, if it has one. This activity is repressed in prion-infected cells for loss
      of-activity prions, [URE3] (the prion of Ure2p) and [PSI] (the prion of Sup35p).
      For gain-of-activity prions, [PIN] (the prion of Rnq1p) and [Het-s] (the prion of
      HET-s), the prion domain is also involved in generating a new activity in
      infected cells. In prion conversion, prion domains polymerize into an amyloid
      filament, switching from a "natively unfolded" conformation into an amyloid
      conformation (stable, protease-resistant, rich in cross-beta structure). For
      Ure2p and probably also Sup35p, the functional domain retains its globular fold
      but is inactivated by a steric mechanism. We review the evidence on which this
      scenario is based with emphasis on filament structure, summarizing current
      experimental constraints and appraising proposed models. We conclude that the
      parallel superpleated beta-structure and a specific beta-helical formulation are
      valid candidates while other proposals are excluded. In both the Ure2p and Sup35p
      systems, prion domain amyloid filaments exhibit polymorphic variation. However,
      once a certain structure is nucleated, it is maintained throughout that filament.
      Electron microscopy of several Ure2p-related constructs indicates that the basis
      for polymorphism lies mainly if not entirely in the prion domain. Filament
      polymorphism appears to underlie the phenomenon of prion "variants" which differ
      in the severity of their phenotype, that is, for Ure2p and Sup35p, the stringency
      with which their activity is switched off. We discuss a possible structural basis
      for this phenomenon.

PMID- 17190615
TI  - From the polymorphism of amyloid fibrils to their assembly mechanism and
      cytotoxicity.
AB  - Extracellular amyloid deposits are present in a variety of diseases. They contain
      amyloid fibrils that arise from the association of proteins or peptides. At the
      molecular level, all these fibrils share a common assembly principle based on a
      conformational change of the protein precursor leading to the formation of a
      cross-beta sheet structure. The smallest observed fibrils in vitro, often called
      protofibrils, are 4-5 nm in diameter. An amyloid fibril is generally composed of
      several of these protofibrils and may adopt different morphologies such as
      ribbons, sheets, or multistranded cables. This polymorphism was observed with
      many different amyloid-forming peptides and proteins using electron microscopy.
      The need to understand the molecular origin of this effect as well as the desire
      to find inhibitors of fibril formation has driven researchers toward the
      dissection of amyloid fibril assembly pathways. We review the current knowledge
      on amyloid polymorphism and discuss recent findings in the field concerning
      amyloid fibril assembly pathways and cytotoxicity mechanisms.

PMID- 17190616
TI  - Structural models of amyloid-like fibrils.
AB  - Amyloid fibrils are elongated, insoluble protein aggregates deposited in vivo in
      amyloid diseases, and amyloid-like fibrils are formed in vitro from soluble
      proteins. Both of these groups of fibrils, despite differences in the sequence
      and native structure of their component proteins, share common properties,
      including their core structure. Multiple models have been proposed for the common
      core structure, but in most cases, atomic-level structural details have yet to be
      determined. Here we review several structural models proposed for amyloid and
      amyloid-like fibrils and relate features of these models to the common fibril
      properties. We divide models into three classes: Refolding, Gain-of-Interaction,
      and Natively Disordered. The Refolding models propose structurally distinct
      native and fibrillar states and suggest that backbone interactions drive fibril
      formation. In contrast, the Gain-of-Interaction models propose a largely native
      like structure for the protein in the fibril and highlight the importance of
      specific sequences in fibril formation. The Natively Disordered models have
      aspects in common with both Refolding and Gain-of-Interaction models. While each
      class of model suggests explanations for some of the common fibril properties,
      and some models, such as Gain-of-Interaction models with a cross-beta spine, fit
      a wider range of properties than others, no one class provides a complete
      explanation for all amyloid fibril behavior.

PMID- 17190617
TI  - Off-label uses of biologics in dermatology: interferon and intravenous
      immunoglobulin (part 1 of 2).
AB  - The introduction of a number of biologic therapies into the market has
      revolutionized the practice of dermatology. These therapies include interferons,
      intravenous immunoglobulin, infliximab, adalimumab, etanercept, efalizumab,
      alefacept, and rituximab. Most dermatologists are familiar with the Food and Drug
      Administration-approved indications of these medications. However, numerous off
      label uses have evolved. As part 1 of a 2-part series, this article will review
      the literature regarding the off-label uses of the interferons and intravenous
      immunoglobulin in dermatology.

PMID- 17190618
TI  - Off-label uses of biologics in dermatology: rituximab, omalizumab, infliximab,
      etanercept, adalimumab, efalizumab, and alefacept (part 2 of 2).
AB  - Recently, dermatologists have witnessed a revolution in our therapeutic
      armamentarium with the development of several novel biologic immunomodulators.
      Although psoriasis remains the only condition in dermatology for which the use of
      biologic immunomodulators has been approved by the Food and Drug Administration,
      these drugs have the potential to significantly impact the treatment of several
      inflammatory conditions in dermatology. This article includes a review of the
      mechanism of action, dosing, and side-effect profile, as well as a review of the
      current literature on off-label uses of the CD20-positive B-cell antagonist
      rituximab, the IgE antagonist omalizumab, the tumor necrosis factor-alpha
      antagonists infliximab, etanercept, and adalimumab, and the T-cell response
      modifiers efalizumab and alefacept.

PMID- 17190619
TI  - Community-acquired methicillin-resistant Staphylococcus aureus.
AB  - Published data confirm that community-acquired methicillin-resistant
      Staphylococcus aureus (MRSA) infections are increasing in incidence in both urban
      and rural settings. The statistical risk is higher for athletes, military
      personnel, prison inmates, intravenous drug abusers, the homeless, children in
      daycare, and certain Native American groups, but the infections are by no means
      restricted to these populations. Roughly 85% of the infections involve the skin
      and subcutaneous tissue, with the most common presentations being an abscess or
      folliculitis. The typical associated gene cassette is quite small and codes only
      for methicillin resistance. Abscesses generally respond to drainage. LEARNING
      OBJECTIVE: At the conclusion of this learning activity, participants should
      recognize groups at high risk for community-acquired MSRA infections and manage
      these infections appropriately.

PMID- 17190620
TI  - The CASH (color, architecture, symmetry, and homogeneity) algorithm for
      dermoscopy.
AB  - BACKGROUND: The color, architecture, symmetry, and homogeneity (CASH) algorithm
      for dermoscopy includes a feature not used in prior algorithms, namely,
      architecture. Architectural order/disorder is derived from current concepts
      regarding the biology of benign versus malignant melanocytic neoplasms.
      OBJECTIVE: We sought to evaluate the accuracy of the CASH algorithm. METHODS: A
      total CASH score (TCS) was calculated for dermoscopic images of 325 melanocytic
      neoplasms. Sensitivity, specificity, diagnostic accuracy, and receiver operating
      characteristic curve analyses were performed by comparing the TCS with the
      histopathologic diagnoses for all lesions. RESULTS: The mean TCS was 12.28 for
      melanoma, 7.62 for dysplastic nevi, and 5.24 for nondysplastic nevi. These
      differences were statistically significant (P < .001). A TCS of 8 or more yielded
      a sensitivity of 98% and specificity of 68% for the diagnosis of melanoma.
      LIMITATIONS: This is a single-evaluator pilot study. Additional studies are
      needed to verify the CASH algorithm. CONCLUSIONS: The CASH algorithm can
      distinguish melanoma from melanocytic nevi with sensitivity and specificity
      comparable with other algorithms. Further study is warranted to determine its
      intraobserver and interobserver correlations.

PMID- 17190621
TI  - Accuracy of standard dermoscopy for diagnosing scabies.
AB  - BACKGROUND: Scabies is a contagious skin infestation caused by the human mite
      Sarcoptes scabiei. The usual reference method for definitive diagnosis is ex vivo
      identification of the mite with microscopic examination of skin scrapings. We
      compared diagnostic accuracy of in vivo dermoscopic (DS) mite identification
      using a pocket handheld low-magnification DS with the reference method. METHODS:
      We conducted a prospective, nonrandomized, evaluator-blinded, noninferiority
      study to compare sensitivities (main outcome) and other diagnostic properties of
      DS and microscopic examination of skin scrapings. Among 756 patients with a
      presumptive diagnosis of scabies consulting in one center, 238 were sequentially
      submitted to the two diagnostic procedures. Three dermoscopists (one expert, two
      inexperienced) were involved. Diagnostic strategies using clinical skills only,
      DS results, and a combination of both were compared. RESULTS: Sensitivities were
      91% (95% confidence interval: 86-96) for DS and 90% (95% confidence interval: 85
      96) for microscopic examination of skin scrapings (P = .005 for noninferiority).
      Specificities were 86% (95% confidence interval: 80-92) for DS and 100% (by
      definition) for microscopic examination of skin scrapings. DS sensitivities were
      similar for the expert and inexperienced dermoscopists, whereas differences were
      observed in specificities. However, diagnostic accuracy of inexperienced
      dermoscopists steadily increased during the study. Compared with clinical-based,
      DS-based treatment decision rule minimized the number of false-positive and false
      negative findings, whereas a treatment decision rule based on combination of
      clinical presumption and DS result drastically reduced the number of patients
      with scabies left untreated. LIMITATIONS: There is no definitive standard for
      ruling out the diagnosis of scabies. CONCLUSIONS: Standard DS with a handheld DS
      is a useful tool for diagnosing scabies, with high sensitivity, even in
      inexperienced hands. It greatly enhances clinical skills for making treatment
      decisions.

PMID- 17190622
TI  - Topical imiquimod in the treatment of infantile hemangiomas: a retrospective
      study.
AB  - BACKGROUND: Active nonintervention remains the mainstay of therapy for most
      uncomplicated infantile hemangiomas (IH) because of their expected involution.
      Topical imiquimod, with its ability to induce the production of interferon, tumor
      necrosis factor-alpha, and the antiangiogenesis factor tissue inhibitor of matrix
      metalloproteinase, has been recently reported to be efficacious in the treatment
      of IH. OBJECTIVE: We sought to evaluate the efficacy of imiquimod 5% cream in the
      treatment of noncomplicated IH and possible side effects. METHODS: A
      retrospective chart review analysis was performed in 18 children (16 girls and 2
      boys) with a median age of 18 weeks (range: 4-256 weeks). A total of 22
      hemangiomas (14 located on head, 3 on genitalia, 2 on trunk, and 3 on
      extremities) were treated with imiquimod 5% cream. Imiquimod was applied 3 times
      weekly in 10 patients and 5 times weekly in 8 patients for a mean duration of 17
      weeks (7-46 weeks). RESULTS: All superficial IH improved, and remission was
      achieved in 4 hemangiomas. There was little improvement in mixed IH with no or
      minimal change in all deep hemangiomas. One case with ulcerated hemangioma
      substantially improved with accelerated ulcer healing and hemangioma size
      reduction. No systemic complication was observed in any of our patients, with
      irritation and crusting being the most common reactive effects. LIMITATIONS: The
      small-sample, retrospective study limits the interpretation of results.
      CONCLUSION: Imiquimod 5% cream may be most effective in superficial IH. There was
      no significant correlation between response and early onset of treatment for any
      IH in our small sample study. Pharmacokinetic analysis and placebo-controlled
      study should follow to ascertain the safety and efficacy of imiquimod 5% cream in
      the pediatric age group.

PMID- 17190623
TI  - Cutaneous sarcoidosis therapy updated.
AB  - The widely accepted standard therapy for cutaneous sarcoidosis includes
      corticosteroids, antimalarials, and methotrexate. However, a better understanding
      of the basic immunopathogenic properties of sarcoidosis has elucidated a number
      of steps critical to the persistence and progression of disease that may be
      vulnerable to treatment by targeted therapy. This article reviews both standard
      and newer therapeutic options for cutaneous sarcoidosis.

PMID- 17190625
TI  - Recurrence rates of primary basal cell carcinoma in facial risk areas treated
      with curettage and electrodesiccation.
AB  - BACKGROUND: The incidence of basal cell carcinoma (BCC) is increasing. Curettage
      and electrodesiccation (CE) are not recommended for BCC treatment at medium- and
      high-risk facial sites. Surgical excision has been proposed as the treatment of
      choice. OBJECTIVE: We sought to evaluate the cumulative recurrence rate (RR) of
      primary BCC in facial areas of medium and high risk after CE. METHODS: This
      nonrandomized, clinical trial enrolled 257 patients with primary BCC located in
      medium- and high-risk facial areas, and treated with 4 or 5 cycles of CE by a
      single operator from a section specializing in BCC CE in a tertiary teaching
      hospital in Oviedo, Spain. Exclusion criteria for study entry included: recurrent
      BCC, fibrosing BCC, ill-defined BCC, and BCC larger than 10 mm in diameter (high
      risk facial sites) or larger than 15 mm in diameter (medium-risk sites); BCC
      smaller than 4 mm; and nonbiopsy-proven BCC. BCCs included in the study were from
      the nose, and paranasal and nasal-labial fold (n = 105); eyelids and canthi (n =
      48); perioral areas (n = 12); ears (n = 11); forehead and temples (n = 48);
      periauricular areas (n = 14); and malar areas and cheeks (n = 19). The primary
      outcome was recurrence of carcinoma, which was clinically evaluated by at least
      two observers in consensus. Data were analyzed using both a life table method and
      Kaplan-Meier analysis. The statistical analysis included best- and worst-case
      scenarios (which means that all cases lost to follow-up were considered as
      recurrences). RESULTS: The 5-year cumulative non-RR in the best-case scenario was
      98.80% (SE 0.70, 95% confidence interval 97.40%-100%); thus, a 5-year cumulative
      RR of 1.20% was found after CE in our medium- and high-risk BCCs of the face
      (best case). The 5-year cumulative non-RR in the worst-case scenario was 79.40%
      (95% confidence interval 78.90%-79.90%); thus, a 5-year cumulative RR of 20.60%.
      LIMITATIONS: Retrospective design with a relatively small number of patients lost
      to follow-up is a study limitation. CONCLUSION: High 5-year cure rates can be
      obtained after CE of primary, nonfibrosing BCCs of medium- and high-risk areas of
      the face performed in a specialized section.

PMID- 17190624
TI  - Role of contact sensitization in chronic urticaria.
AB  - We tested the hypothesis that contact allergy plays a role in chronic urticaria,
      and included the Italian series of patch tests in the diagnostic workup. Of 121
      patients with chronic urticaria, 50 (41%) tested positive to contact allergens.
      In all patients, avoidance measures led to a complete remission within 1 month.
      We suggest that testing for contact sensitization can be helpful in the
      management of chronic urticaria.

PMID- 17190626
TI  - Cutaneous vascular deposition of C5b-9 and its role as a diagnostic adjunct in
      the setting of diabetes mellitus and porphyria cutanea tarda.
AB  - BACKGROUND: The cutaneous lesions of diabetes mellitus (DM) and porphyria cutanea
      tarda (PCT) exhibit distinctive microvascular changes including basement membrane
      zone thickening and lamellation, morphologically appearing as hyaline-like
      alterations of the vessel wall. Immunofluorescence demonstrates homogeneous
      mantles of immunoglobulin in the microvasculature. The staining intensity is
      variable and in some cases can closely approximate those immunofluorescent
      changes seen in photoaged skin. OBJECTIVE: The purpose of this study was to
      establish an association between the microvascular changes seen in the skin from
      patients with DM and PCT and the presence of C5b-9 deposition, potentially
      defining the C5b-9 assay as an additional diagnostic adjunct. METHODS: Routine
      light microscopy and immunofluorescence studies were conducted on skin biopsy
      specimens from 14 patients with cutaneous manifestations of DM and 17 patients
      with PCT. The immunofluorescence profile included IgG, IgM, IgA, C3, C3d, C4d,
      and C5b-9. RESULTS: Fourteen of 14 DM and 17 of 17 PCT skin biopsy specimens
      revealed extensive granular and homogeneous vascular deposition of C5b-9; a
      similar pattern was observed for C3d and C4d. Control specimens from patients
      without DM and PCT, where C5b-9 was not an expected immunoreactant, were
      negative. Positive controls were cases of vasculitis, scleroderma, and
      dermatomyositis without DM and PCT where C5b-9 deposition was expected. C5b-9
      deposition was observed and was of lesser magnitude than that encountered in
      patients with PCT or DM. LIMITATIONS: We were unable to obtain detailed clinical
      information on some of the diabetic patients in regards to significant
      extracutaneous vascular complications. In addition, a correlation between
      hemoglobin 1 Ac levels and the extent of C5b-9 deposition could not be
      ascertained as the serum levels for hemoglobin 1 Ac were unknown. CONCLUSION:
      Granular and homogeneous deposits of C5b-9 in vessels, along with homogeneous
      deposits of immunoglobulin within the blood vessels, are characteristic
      immunofluorescence findings in patients with DM and PCT. In regards to potential
      mechanisms of C5b-9 deposition, decreased metabolism of C5b-9 due to
      glycosylation of CD59 in the setting of DM and activation of complement by
      irradiated porphyrins in PCT are proposed. The extent of C5b-9 deposition
      suggests that this complex may play a pathogenetic role in the evolution of
      microvascular injury in patients with DM and PCT.

PMID- 17190628
TI  - Systematic review of rosacea treatments.
AB  - BACKGROUND: Rosacea is a common chronic skin and ocular condition. It is unclear
      which treatments are most effective. We have conducted a Cochrane review of
      rosacea therapies. This article is a distillation of that work. OBJECTIVE: We
      sought to assess the evidence for the efficacy and safety of rosacea therapies.
      METHODS: Multiple databases were systematically searched. Randomized controlled
      trials in people with moderate to severe rosacea were included. Study selection,
      assessment of methodologic quality, data extraction, and analysis were carried
      out by two independent researchers. RESULTS: In all, 29 studies met inclusion
      criteria. Topical metronidazole is more effective than placebo (odds ratio 5.96,
      95% confidence interval 2.95-12.06). Azelaic acid is more effective than placebo
      (odds ratio 2.45, 95% confidence interval 1.82-3.28). Firm conclusions could not
      be drawn about other therapies. LIMITATIONS: The quality of the studies was
      generally poor. CONCLUSIONS: There is evidence that topical metronidazole and
      azelaic acid are effective. There is some evidence that oral metronidazole and
      tetracycline are effective. More well-designed, randomized controlled trials are
      required to provide better evidence of the efficacy and safety of other rosacea
      therapies.

PMID- 17190629
TI  - Acrodermatitis enteropathica and an overview of zinc metabolism.
AB  - Acrodermatitis enteropathica is a rare autosomal recessive disorder of zinc
      deficiency. The genetic defect has been mapped to 8q24 and the defective gene
      identified as SLC39A4, which encodes the zinc transporter Zip4. The diagnosis is
      made by way of clinical presentation together with histopathology and laboratory
      tests. Here we provide an overview of zinc metabolism and a description of
      inherited and acquired zinc deficiency.

PMID- 17190630
TI  - Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an
      international consensus. International Society for Photodynamic Therapy in
      Dermatology, 2005.
AB  - Topical photodynamic therapy (PDT) is used to treat nonmelanoma skin cancers,
      such as actinic keratoses, Bowen's disease, and basal cell carcinoma (superficial
      and nodular). This article presents up-to-date, practical, evidence-based
      recommendations on the use of topical PDT using 5-aminolevulinic acid or methyl
      aminolevulinate for the treatment (and prevention) of nonmelanoma skin cancers. A
      systematic literature review was conducted (using MEDLINE), and recommendations
      were made on the basis of the quality of evidence for efficacy,
      safety/tolerability, cosmetic outcome, and patient satisfaction/preference.
      Topical PDT is highly effective in the treatment of actinic keratoses, Bowen's
      disease, superficial and thin nodular basal cell carcinomas, with cosmesis
      typically superior to that achieved with existing standard therapies. PDT may
      also be a means of preventing certain nonmelanoma skin cancers in
      immunosuppressed patients.

PMID- 17190631
TI  - Screening for melanoma.
AB  - Dialogues in Dermatology, a monthly audio program from the American Academy of
      Dermatology, contains discussions between dermatologists on timely topics.
      Commentaries from Dialogues Editor-in-Chief Warren R. Heymann, MD, are provided
      after each discussion as a topic summary and are provided here as a special
      service to readers of the Journal of the American Academy of Dermatology.

PMID- 17190632
TI  - Surgical pearl: Use of digital Vernier calipers for measurement of lesional and
      excisional dimensions.

PMID- 17190633
TI  - Cosmetic versus medical dermatology patients.

PMID- 17190634
TI  - Not just sunscreen: caps.

PMID- 17190635
TI  - Keratin 17/interferon-gamma autoimmune loop as a vicious circle driving psoriasis
      pathogenesis.

PMID- 17190637
TI  - Acne and iodine: reply.

PMID- 17190638
TI  - An educational brochure helps improve patients' understanding of residents' role
      and level of training.

PMID- 17190639
TI  - Pilot study of a skin cancer education curriculum for medical students.

PMID- 17190640
TI  - Acute myelogenous leukemia in a patient receiving etanercept for psoriasis.

PMID- 17190641
TI  - Classic pseudoxanthoma elasticum in a patient with sickle cell disease.

PMID- 17190642
TI  - Keratoacanthomas associated with sorafenib therapy.

PMID- 17190643
TI  - Antimicrobial activity of diterpenoids from hairy roots of Salvia sclarea L.:
      salvipisone as a potential anti-biofilm agent active against antibiotic resistant
      Staphylococci.
AB  - The antimicrobial activities of crude dichloromethane fractions from acetone
      extracts of Agrobacterium rhizogenes transformed roots and roots of field-grown
      plants of Salvia sclarea as well as four pure abietane diterpenoids isolated from
      the hairy root cultures were determined. The growth of Gram-positive bacteria
      (Staphylococcus aureus, S. epidermidis, Enterococcus faecalis) but not Gram
      negative ones (Escherichia coli, Pseudomonas aeruginosa) or pathogenic fungi
      (Candida albicans) was inhibited by fractions tested at concentrations of 37.5
      75.0 microgml(-1). Abietane diterpenoids: salvipisone, aethiopinone, 1
      oxoaethiopinone and ferruginol were shown to be bacteriostatic as well as
      bacteriocidal for the cultures of S. aureus and S. epidermidis strains,
      regardless of their antibiotic susceptibility profile. This was demonstrated by
      using simultaneously the optical density measuring method and 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide-reduction assay. The
      highest activity was shown by salvipisone which demonstrated also a very
      interesting activity when its effect on 24-h-old staphylococcal biofilm cells
      viability was examined. It limited the survival of biofilms formed by S. aureus
      as well as by S. epidermidis, putting this compound to the list of potential anti
      biofilm agents, better than most of known antibiotics.

PMID- 17190644
TI  - In vitro and in vivo leishmanicidal activity of Dysoxylum binectariferum and its
      fractions against Leishmania donovani.
AB  - The leishmanicidal effect of crude ethanolic extract of stem bark of Dysoxylum
      binectariferum and its fractions has been investigated against Leishmania
      donovani, the causative agent of visceral leishmaniasis. Ethanolic extract was
      lethal to promastigotes as well as amastigote forms in macrophage system at the
      concentration of 100 microg/ml. Chloroform fraction significantly inhibited
      promastigote multiplication and was also active against amastigotes in infected
      J774A.1 macrophages at 100 microg/ml. Hexane fraction was moderately active and
      the other fractions were inactive against both the forms. When tested in vivo in
      hamsters, ethanolic extract was toxic at 500 mg/kg whereas exhibited marginal
      activity (67.7+/-5.3%) at 250 mg/kg x 5, p.o. on day 7 post treatment (p.t.)
      which increases slightly (69+/-4.7) by day 30 p.t. Chloroform and n-hexane
      fractions exhibited 64.3+/-4% and 47.8+/-4.6% parasite inhibition at the dose of
      100 mg/kg x 5 p.o., respectively. The pure compound, rohitukine, obtained from
      chloroform fraction showed weaker in vitro activity and was ineffective in
      infected hamsters. The lead potential of this plant need further investigations.

PMID- 17190645
TI  - Immunostimulatory principles from Chlorella pyrenoidosa--part 1: isolation and
      biological assessment in vitro.
AB  - Our proprietary preparation obtained by extraction of Chlorella pyrenoidosa
      cells, ONC-107 (Respondin), was recently found to selectively boost antibody
      response to the influenza vaccine in a human clinical trial. Respondin is a
      potent stimulator of mouse B cell proliferation and an activator of macrophages.
      Bioactivity-guided resolution concluded that Respondin is composed of a mixture
      of immunostimulatory principles of different chemical nature. A combination of
      size exclusion, anion exchange and hydrophobic interaction chromatography
      revealed that the bulk of the immunostimulatory activity resides in
      polysaccharide/protein complexes with molecular masses larger than 100 kDa that
      are composed primarily of galactose, rhamnose and arabinose.

PMID- 17190647
TI  - Targeting the vascular endothelial growth factor pathway in the treatment of
      human malignancy.
AB  - Over 30 years ago, it was proposed that blocking new blood vessel formation would
      significantly inhibit solid tumor growth and hence, limit cancer progression.
      Efforts guided by this philosophy have resulted in a better understanding of the
      molecular basis of tumor angiogenesis. The first successful therapeutic to emerge
      from this work, an antibody (bevacizumab) targeting the vascular endothelial
      growth factor (VEGF), was recently approved for the treatment of colorectal
      cancer. Additional positive clinical data with bevacizumab in the treatment of
      breast and lung carcinoma have also been reported. These clinical achievements
      have validated the approach of anti-angiogenesis therapy for cancer and provided
      further confirmation for antibodies as a therapeutic class in this disease.
      Nevertheless, important unanswered questions with regard to preclinical and
      clinical results of VEGF pathway inhibitors remain. For example, preclinical
      models with a number of VEGF pathway inhibitors suggest that these agents would
      have significant clinical activity on their own; yet, clinical activity in
      patients with bevacizumab or other VEGF pathway inhibitors as monotherapy have
      been disappointing. Moreover, while bevacizumab is approved for the treatment of
      colorectal cancer in combination with cytotoxics, the mechanism for the benefits
      of this combination are still poorly understood, with a number of viable
      mechanisms under active experimental evaluation. The 3-8-month survival benefit
      in colorectal cancer patients treated with bevacizumab is a positive step
      forward. However, improving our understanding of the mechanism for these effects,
      as well as the mechanism underlying the inability as yet to achieve greater
      effects, is needed in order to follow up on the positive clinical results with
      improved strategies. This review discusses the experimental results surrounding
      the current status of our understanding of the mechanism of action of VEGF
      signaling inhibitors, and the potential for utilizing these agents in the future
      so that clinical benefits will be measured in years rather than months.

PMID- 17190648
TI  - The role of death receptor ligands in shaping tumor microenvironment.
AB  - Death receptor ligands (FasL, TRAIL) activate apoptosis in cells expressing the
      cognate receptors. Evidence suggests that these ligands also deliver pro
      inflammatory signals. In the tumor microenvironment, "Fas counterattack" mounted
      by tumors against immune cells is mediated by tumor-associated FasL. But death
      ligands crosslinking their receptors also induce inhibition of apoptosis and
      activation of the transcription factor, NFkappaB, with a subsequent burst of pro
      inflammatory cytokine production and tumor growth promotion. NFkappaB, a key link
      between inflammation and cancer, regulates dual activities of death ligands,
      depending on molecular signals in the tumor microenvironment. This paper focuses
      on death ligands as an example of the extensive repertoire of strategies devised
      by tumors for escape from immune control.

PMID- 17190649
TI  - Elevation of pro-inflammatory cytokines, C-reactive protein and cardiac troponin
      T in chronic renal failure patients on dialysis.
AB  - Chronic renal failure (CRF) patients suffer from a chronic inflammation. They are
      at increased risk of cardiovascular disease. In order to investigate this
      inflammatory process and cardiovascular risk factors associated with
      haemodialysis (HD) and peritoneal dialysis (PD), we compared serum/plasma pro
      inflammatory cytokines, C-reactive protein (CRP), and cardiac troponin T (cTnT)
      of 146 CRF patients treated or not treated with PD or HD. Serum cytokines and CRP
      as well as plasma cTnT were measured by enzyme-linked immunosorbent assay,
      chemiluminescence immunoassay, and electrochemiluminescence immunoassay,
      respectively. Results indicated that serum interleukin (IL)-18 concentrations
      were significantly higher in PD and low creatinine clearance pre-dialysis CRF
      (LCC) patients than HD patients (both p < 0.05). IL-6 and tumour necrosis factor
      (TNF)-alpha concentrations were significantly higher in PD patients than LCC
      patients (both p < 0.01). Serum hsCRP and plasma cTnT in HD were significantly
      higher than LCC (both p < 0.01). The elevation of pro-inflammatory cytokines
      should play an important role in the chronic inflammation and increased
      cardiovascular risk of CRF patients on dialysis. We are evaluating further the
      diagnostic and prognostic applications of pro-inflammatory cytokines and
      biochemical inflammatory markers for these patients.

PMID- 17190650
TI  - Contact activation via ICAM-1 induces changes in airway epithelial permeability
      in vitro.
AB  - The role of ICAM-1 in contact activation of the bronchial epithelial cells is
      elucidated. Direct contact between epithelial cells and leukocytes is required to
      change transepithelial electrical resistance (TER) of the epithelium. Migration
      of human neutrophils across the layers of cultured human airway epithelial cells
      (Calu-3) or primary cow tracheal epithelial cells was induced by an fMLP
      gradient. Migrating neutrophils decreased TER and increased permeability to
      albumin. Monoclonal antibodies to ICAM-1 reduced neutrophil migration, thus
      reducing the changes in TER and changes in the epithelial permeability to
      albumin. By confocal microscopy, ERK1/2 was found to be locally activated in the
      epithelial cells at the sites of migration and cross-linking of ICAM-1. Blockade
      of ERK1/2 by PD98059 decreased the changes in TER which were induced by ICAM-1
      cross-linking. Contact activation of the bronchial epithelial cells, involving
      ICAM-1 via local activation of ERK1/2, is an important mechanism of alteration of
      the bronchial epithelial permeability.

PMID- 17190651
TI  - Normal human plasma anti-beta-glucoside antibody has markedly elevated IgA
      content and binds fungal and yeast polysaccharides.
AB  - Normal human plasma antibody that recognizes beta-linked glucoside moiety was
      purified by affinity chromatography on cellulose. The anti-beta-glucoside
      antibody had three times higher IgA to IgG ratio and substantially higher
      polymeric IgA content than total serum immunoglobulins. Cellobiose and other beta
      glucosides were best inhibitors of its binding to polystyrene microwell-coated
      polysaccharides. In synthetic glycoproteins made by conjugating disaccharides to
      hemoglobin or bovine serum albumin, cellobiose, unlike lactose or maltose, was
      sugar-specifically recognized by the antibody. It also recognized polystyrene
      well-coated beta1-->3 linked glycans of Saccharomyces cerevisiae, Candida
      albicans and of barley in decreasing order of affinity. Its sugar-binding site
      could thus accommodate beta-glucoside with or without substitution at C4 and C3.
      High IgA content along with the capacity to bind common microbial and dietary
      antigens pointed to the immune inflammatory potential of the antibody.

PMID- 17190652
TI  - Human purified CD8+ T cells: Ex vivo expansion model to generate a maximum yield
      of functional cytotoxic cells.
AB  - CD8+ T cells are a critical component of the cellular immune response. They play
      an important role in the control of viral infection and eliminating cells with
      malignant potential. However, attempts to generate and expand human CD8+ T cells
      in vitro for an adoptive immunotherapy have been conducted with limitation of the
      very low frequency of CD8+ T cells in blood. Therefore, several expansion
      protocols have been developed to obtain large and efficient numbers of human CD8+
      T cells for use in adoptive immunotherapies. In this study various common culture
      conditions using different cytokines IL-2, IL-4, IL-7, IL-10, IL-12 and IL-15 and
      autologous feeders and sera were investigated to expand human purified CD8+ T
      cells. The importance and the influence of these factors on the growth and
      phenotype of CD8+ T cell were assessed by serially sampling cultures using flow
      cytometry. We demonstrated that combination of IL-2 (50 U/ml) and autologous
      feeders induced maximal CD8+ T cell proliferation (40-50 folds) compared to other
      cytokines. Immunophenotypic analysis of cultured cells showed that expanded CD8+
      T cells were activated and differentiated. Furthermore our expansion model also
      demonstrated that expanded CD8+ T cells are functionally cytotoxic active by
      killing Allogeneic LCLs cells. In conclusion, we have developed a reliable,
      simple method that uses minimal cell numbers to generate a high yield of
      functional cytotoxic CD8+ T cells, which can be used for the development of
      cellular immunotherapies.

PMID- 17190653
TI  - Black grape and garlic extracts protect against cyclosporine a nephrotoxicity.
AB  - The aim of this study was to determine if the natural antioxidant foods, dried
      black grape and garlic, protect against cyclosporine nephrotoxicity. Forty-two
      Sprague-Dawley rats were given Cyclosporine A (CsA) orally for 10 days, with the
      antioxidant food supplementation begun 3 days before CsA treatment and continued
      during the study period (totaling 13 days). In each group (control, CsA alone,
      CsA plus black grape, CsA plus aqueous garlic extract, aqueous garlic extract
      alone and black grape alone), there were 7 animals. At the end of the study
      period, the animals were sacrificed; their kidneys were removed and prepared for
      biochemical and histopathological investigations. Oxidant (xanthine oxidase
      enzyme and malondialdehyde) and antioxidant (superoxide dismutase, glutathione
      peroxidase and catalase enzymes) parameters were measured in the kidney tissues
      of the groups. Histopathological examinations of the tissues were also performed.
      It has been found that CsA creates oxidant load to the kidneys through both
      xanthine oxidase activation and impaired antioxidant defense system, which
      accelerates oxidation reactions in the kidney tissue. Supplementation with either
      dried black grape or aqueous garlic extract led to reduced malondialdehyde level
      in the kidney tissue possibly, by preventing oxidant reactions. In conclusion,
      the results suggest that impaired oxidant/antioxidant balance may play part in
      the CsA-induced nephrotoxicity, and some foods with high antioxidant power may
      ameliorate this toxicity, in agreement with studies with antioxidant vitamins.

PMID- 17190655
TI  - Surgery without scars: the new frontier of minimally invasive surgery?
      Controversies, concerns and expectations in advanced operative endoscopy.

PMID- 17190656
TI  - Mucosectomy for high-grade dysplasia in Barrett's esophagus.
AB  - Reports on the natural history of high-grade dysplasia (HGD) are sometimes
      contradictory, but suggest that 10-30% of patients with HGD in Barrett's
      esophagus (BE) will develop a demonstrable malignancy within five years of the
      initial diagnosis. Surgery has to be considered the best treatment for HGD or
      superficial carcinoma, but is contraindicated in patients with severe
      comorbidities. Non-surgical treatments such as intensive endoscopic surveillance,
      endoscopic ablative therapies, and endoscopic mucosal resection (EMR) have been
      proposed. EMR is a newly developed procedure promising to become a safe and
      reliable non-operative option for the endoscopic removal of HGD or early cancer
      within BE. It is important to assess the depth of invasion of the lesion and
      lymph node involvement before choosing EMR. This technique permits more effective
      staging of disease obtaining a large sample leading to a precise assessment of
      the depth of malignant invasion. Complications such as bleeding and perforation
      may occur, but can be treated endoscopically. Trials are needed to compare
      endoscopic therapy with surgical resection to establish clear criteria for EMR
      and ablative therapies.

PMID- 17190657
TI  - Metal stents for malignant colorectal obstruction.
AB  - Malignant obstruction of the colon occurs in 7-25% of patients with colorectal
      cancer. As emergency laparotomy is reported to have relatively high morbidity and
      mortality rate, there is a need for alternative procedures with reduced
      complication rates. Over the last decade colorectal stenting has been reported as
      an alternative endoscopic method to relieve acute colonic obstruction. With the
      availability of more sophisticated stents and stent delivery systems, this
      approach has been used as a palliative method and as a pre-operative bridge to
      facilitate one-stage surgical resection of primary colonic tumors. Technical and
      clinical successes have been reported in 80-100% of treated patients. Distal
      lesions are more common and theoretically easier to stent although lesions within
      the ascending colon have been successfully managed. Minor complications include
      transient anorectal pain, tenesmus and rectal bleeding. However, stent migration
      and colonic perforation are also well recognized. Despite the fact that no
      randomized controlled studies have yet been performed, literature data show that
      colonic stenting is a safe and effective procedure and can reduce costs, avoiding
      the need for colostomy and improving the quality of life of patients with
      advanced disease.

PMID- 17190658
TI  - Operative colonoscopy in cancer patients.
AB  - Gastrointestinal endoscopy has experienced tremendous developments in technology
      and equipment over the past decades. It is not only a diagnostic tool, but it
      also allows some interventional treatments in benign and malignant digestive
      diseases. Operative colonoscopy has been used to perform curative treatment of
      various kinds of polyps, flat and carpet-like adenomas and early colorectal
      carcinomas. Endoscopic palliative treatment strategies, such as the placement of
      self-expandable metal stents (SEMS), laser ablation, photodynamic therapy (PDT),
      argon plasma coagulation (APC), electrocoagulation, and injection therapy, have
      been proved to effectively alleviate advanced colorectal cancer (CRC) associated
      symptoms and maintain or improve the quality of the patient's remaining life.

PMID- 17190659
TI  - Endoluminal fundoplication (ELF)--evolution of EsophyX, a new surgical device for
      transoral surgery.
AB  - A novel endoluminal fundoplication (ELF) technique using a trans-oral and
      fastener-deploying device (EsophyX, EndoGastric Solutions) was developed and
      evaluated for feasibility, safety and the treatment of gastroesophageal reflux
      disease (GERD) in a series of bench, animal, human (phase 1, phase 2, commercial
      registry) studies. The studies verified biological compatibility, durability and
      non-toxicity of the polypropylene fasteners as well as the feasibility of the ELF
      technique. The results of the preclinical testing indicated that the EsophyX
      device was shown to be safe, and capable of deploying fasteners directly into
      tissue and forming an interrupted suture line at the base of the gastro
      esophageal valve (GEV). Moreover, the studies demonstrated that the ELF technique
      performed using the EsophyX device resulted in the creation of new GEVs of 3-5 cm
      in length and a circumference of 200 degrees -310 degrees , which maintained
      their anatomical aspects at six months. The ELF-created GEVs appeared similar to
      those created by laparoscopic anti-reflux surgery (LARS). The ELF procedure also
      resulted in reduction of all small hiatal hernias (2 cm in size) and restoration
      of the angle of His. The ELF procedure provides an anatomical approach similar to
      that of LARS for the treatment of GERD.

PMID- 17190660
TI  - Endoluminal fundoplication.
AB  - In GERD patients in whom pharmacological therapies are ineffective and anti
      reflux surgery is not indicated, a viable option could be proposed. To date,
      several endoscopic antireflux procedures, involving sewing, injection and/or
      implant, and radiofrequency are available. The sewing techniques demonstrated
      good clinical results, with reduction in proton pump inhibitors consumption;
      despite significant changes in esophageal manometry and/or acid exposure time
      reduction and healing of esophagitis were noted only in few patients.

PMID- 17190661
TI  - Endoluminal fundoplication--the Hill procedure.
AB  - Endoluminal operations for reflux are currently limited by the inability to
      visualise and manipulate structures outside the wall of the gut. This may be
      possible using endoscopic ultrasound (EUS). The aim of this study was to define
      EUS-anatomy of structures outside the gut which influence reflux; to place
      stitches in the median arcuate ligament (MAL); to perform posterior gastropexy
      (Hill procedure) and test the feasibility of crural repair under EUS control in
      pigs. In survival experiments in 14 pigs, using linear array echo-endoscopes the
      MAL and part of the right crus were identified and punctured with a needle, which
      served as a carrier for a tag and thread. These were anchored into the muscle. An
      endoscopic sewing device was used allowing stitches to be placed through a 2.8 mm
      accessory channel to any predetermined depth. New methods allowed knot-tying and
      thread-cutting through the 2.8 mm channel of the echo-endoscope. Stitches were
      placed through the gastric wall into the MAL and one just beyond the wall of the
      lower esophageal sphincter (LES). They were tied together and locked against the
      gastric wall. Preoperative manometry showed a median LES pressure of 11 mm/Hg and
      21 mm/Hg after stitch placement (p = 0.0028). The length of the LES increased
      from median 2.8 cm pre-procedure to 3.5 cm post-procedure. At post mortem, the
      force to pull the tags out of the MAL was 2.8 kg median. This study shows that
      transgastric gastro-esophageal reflux surgery using stitching under EUS control
      can significantly increase the lower oesophageal sphincter pressure in pigs.

PMID- 17190662
TI  - Principle and history of Natural Orifice Translumenal Endoscopic Surgery (NOTES).
AB  - The field of gastrointestinal endoscopy has been witnessing major advances over
      the last five decades. Developing from flexible endoscopy to endoscopic
      retrograde cholangiopancreatography (ERCP) in the 1950's and 70's to endoscopic
      ultrasound in the 80's, endoscopic technology has been transformed from serving
      purely diagnostic purposes to therapeutic applications. One recent major advance
      is the notion of using the flexible endoscope, taking it beyond the
      gastrointestinal lumen into what lies beyond the confines of the gastrointestinal
      tract. Natural orifice translumenal surgery offers the exciting potential to be
      safer, less invasive and possibly more cost-effective than the traditional open
      surgical or laparoscopic approach. The history and principles of natural orifice
      translumenal endoscopic surgery (NOTES), along with future implications, are
      outlined in this article.

PMID- 17190663
TI  - Development of advanced endoscopes for Natural Orifice Transluminal Endoscopic
      Surgery (NOTES).
AB  - Natural orifice transluminal endoscopic surgery (NOTES) is a hybrid procedure
      which uses flexible endoscopic technology to perform laparoscopic surgical
      procedures within the abdominal cavity. Initial reports of animal studies
      describe the use of standard endoluminal endoscopes to accomplish intra-abdominal
      surgeries. Current flexible scopes suffer from several deficiencies which make
      them unlikely to be able to be used for large scale human NOTES experiences. This
      review analyzes the deficiencies of current endoscopes, discusses the
      requirements of the ideal NOTES endoscope and reviews some of the possible
      "endoscopes of the future" that are being developed for the next generation of
      surgery. Discussion focuses on the "R" scope (Olympus, Tokyo, Japan) and the
      Transport and Cobra scopes (USGI Medical, San Capistrano, CA).

PMID- 17190664
TI  - Endoluminal minirobots for transgastric peritoneoscopy.
AB  - The performance of surgeries through small incisions or natural orifices
      minimizes the invasiveness to the patient as compared to open procedures.
      However, the constraints on visual feedback and dexterity limit the scope of
      these procedures. Recent robotic technologies attempt to mitigate these
      constraints for flexible endoscopy and laparoscopy. Much of the current work in
      flexible endoscopy is in the development of a fully autonomous endoscope capable
      of providing the surgeon with better control. Advancements in laparoscopic
      technologies have demonstrated abilities to improve visualization and dexterity
      through telerobotics and in vivo robotics. The application of new robotic
      technologies in flexible endoscopy and laparoscopy to natural orifice surgery
      promises to further benefit the patient by eliminating abdominal incisions,
      scarring, and the pain associated with these incisions. The safety and
      feasibility of such robotic technology has been successfully demonstrated for
      natural orifice transluminal endoscopic surgery (NOTES) in animal models.

PMID- 17190665
TI  - Endoscopic management of uterine fibroids.
AB  - Uterine fibroids are very common, but their relationship to fertility is still
      controversial. Data in relation to fibroids and fertility mainly come from
      retrospective case series and prospective uncontrolled trials. Although some
      authors advocate prospective controlled studies, it is unlikely that an easy
      answer will be found due to considerable variations in location, size and number
      of fibroids, presence of additional infertility factors and variation of surgical
      techniques. Submucosal fibroids are more likely to be associated with menstrual
      disorders and subfertility, and hysteroscopic myomectomy has been accepted as the
      standard treatment for them. Treatment of submucosal fibroids may be associated
      with better reproductive outcomes. There is bigger controversy over the impact of
      intramural and subserosal fibroids on fertility. Laparoscopic myomectomy is now
      used by a large number of groups for removal of these fibroids in selected cases,
      but still remains a challenging procedure which requires advanced laparoscopic
      skills. Its advantages over open myomectomy include reduced postoperative pain,
      shorter hospitalization, quicker recovery, reduced febrile morbidity and blood
      loss. It may also reduce the risk of postoperative adhesion formation. There are
      now large numbers of pregnancies following laparoscopic myomectomy and the risk
      of uterine rupture in future pregnancies seems to be very low with good surgical
      technique.

PMID- 17190666
TI  - Prospective patient and physician preferences for stimulation or no stimulation
      in IVF.
AB  - OBJECTIVE: The aim is to explore the preferences of female patients and
      physicians for IVF in three natural cycles compared to one stimulated cycle and
      to investigate which factors predict these preferences. STUDY DESIGN: A
      questionnaire about IVF preference was administered initially to 105 patients
      between 36 and 42 years, who were on the waiting list for their first or second
      IVF attempt. In addition a questionnaire was sent to 56 physicians of Dutch IVF
      centres. The participants were asked for their preferences at different success
      rates based on treatment trade-off scenarios. Finally, information on
      demographic, psychological and other predictors for treatment choice were
      collected. RESULTS: Complete data were obtained in 69 female patients (67%) and
      27 physicians (49%). At a success rate for a life birth of 17% for both
      treatments, IVF in three natural cycles is preferred by 78% of the patients and
      physicians. Half of the patients and physicians still preferred natural cycle
      treatment at a success rate of 13%. Anxiety for hormone injections was the only
      significant predictor for patients' preferences. CONCLUSION: There seems to be a
      latent demand for IVF in the natural cycle related to anxiety for hormone
      injections.

PMID- 17190667
TI  - Lesbian intra-partner oocyte donation: a possible shake-up in the Garden of Eden?
AB  - Treatment of same-sex couples using infertility therapies has become more
      acceptable over the years, but remains controversial. In December 2005, two law
      changes came into force in the UK that impact same-sex couples. Firstly, the
      Civil Partnership Act 2004 acknowledged legal relationships between same-sex
      couples; and secondly, the Adoption and Children Act 2002 allowed same-sex
      couples to adopt. In view of these law changes, it is timely to consider
      procreation in same-sex couples and, particularly, the possibility of intra
      partner oocyte donation within a lesbian relationship. Such treatment would
      require one female partner to provide the oocyte and the other female partner to
      act as embryo recipient. The embryo(s) could be created using IVF with registered
      anonymous donor sperm. The novelty of allowing a lesbian couple to cause a
      pregnancy in this way could allow the recipient to give birth to a baby that was
      genetically related to her partner. If society finds this acceptable, intra
      partner oocyte donation using donor sperm for IVF could successfully provide a
      family for lesbian couples, offering an alternative to individual donor
      insemination. The ethical aspects of the treatment are discussed.

PMID- 17190668
TI  - Seasonal variation in assisted conception cycles and the influence of
      photoperiodism on outcome in in vitro fertilization cycles.
AB  - The effect of seasonality and daylight length on mammalian reproduction leading
      to spring births has been well established, and is known as photoperiodism. In
      assisted reproduction there is much greater uncertainty as to the effect of
      seasonality. This was a 4-year retrospective analysis of 2709 standardised cycles
      of IVF/ICSI. Data was analysed with regard to the 1642 cycles occurring during
      the months of extended daylight (Apr-Sept) and those 1067 cycles during winter
      months of restricted light length (Oct-Mar). The results showed that there was
      significant improvement in assisted conception outcomes in cycles performed in
      summer (lighter) months with more efficient ovarian stimulation 766iu v880iu/per
      oocyte retrieved (p=0.006). There was similarly a significantly improved
      implantation rate per embryo transferred 11.42% vs 9.35% (p=0.011) and greater
      clinical pregnancy rate 20% vs 15% (p=0.0033) during summer cycles. This study
      appears to demonstrate a significant benefit of increased daylight length on
      outcomes of IVF/ICSI cycles. Whilst the exact mechanism of this is unclear, it
      would seem probable that melatonin may have actions at multiple sites and on
      multiple levels of the reproductive tract, and may exert a more profound effect
      on outcomes of assisted conception cycles than has been previously considered.

PMID- 17190671
TI  - Effect of temporary transfers to 14 h on age at first egg in domestic pullets
      reared on 8-h photoperiods.
AB  - 1. Brown-egg pullets were reared on 8-h photoperiods and temporarily transferred
      at 80 d of age to 14-h photoperiods for 2, 4, 6, 8, 10 or 12 d. Controls were
      either maintained on 8 h or permanently transferred to 14 h at 80 d. 2. Pullets
      given 8 or 12 long days matured 8-9 d earlier than constant 8-h controls, but 22
      23 d later than pullets transferred permanently to long days. Mean age at first
      egg for the groups given 2, 4, 6 or 10 d of 14-h days were not significantly
      different from the 8-h controls. The mean weight of first egg and body weight at
      first egg for the temporarily-photostimulated groups were not significantly
      different from constant 8-h controls, but egg weights were > or = 5.1 g and body
      weights at first egg > or = 200 g heavier than the birds transferred permanently
      to 14 h. 3. It is concluded that up to 6 temporary long days may be given (from
      80 d of age) without affecting the timing of sexual maturity, but that the
      provision of 8 or more long days will accelerate sexual development, thought not
      to the extent of a permanent transfer, in most birds within a flock. A regression
      analysis of the ages at which the first and last birds in the groups given 6, 8,
      10 or 12 long days matured suggested that about 20 d of photostimulation are
      required to achieve a mean age at first egg similar to that of birds permanently
      transferred to long days.

PMID- 17190669
TI  - Research as a therapeutic experience? An investigation of women's participation
      in research on ending IVF treatment.
AB  - BACKGROUND: Women participate in research for many reasons, some of them
      therapeutic. This paper retrospectively analyses women's motivations for
      participating in a study on decision making at the end of in vitro fertilization
      (IVF) treatment. METHODS: A mixed methods study conducted by a practising midwife
      had focused on women's experiences of stopping IVF treatment after one or more
      unsuccessful attempts, and raised awareness of women's motivations for
      participating. Thematic analysis of interview transcripts permitted issues raised
      by the participants in the context of 'research as a therapeutic experience' to
      be explored. RESULTS: Reasons for participating in the study included: (1)
      altruism; (2) appreciation/gratitude for care received; (3) the need to debrief;
      and (4) gaining self-awareness and readjustment, which challenged the acceptance
      of childlessness. Reasons for using the research study as 'a therapeutic
      experience' in the context of failed IVF may be attributed to: (1) access to
      direct clinical care and advice; (2) opportunity for self-reflection and
      rationalization; (3) acceptance of reality; (4) resolution of conflict; and (5)
      opportunity to unburden themselves. CONCLUSION: Women appeared to use the
      interview process to reassure themselves about decisions made, and to seek direct
      clinical advice on whether to continue IVF using donor gametes.

PMID- 17190672
TI  - Differential effects of 4 types of environmental enrichment on aggressive
      pecking, feather pecking, feather loss, food wastage and productivity in Japanese
      quail.
AB  - 1. We examined the effects of 4 types of environmental enrichment (foraging
      opportunities, structural complexity, sensory stimulation/novelty, and social
      companionship) on aggressive and feather pecking, feather condition, food
      wastage, body weight, feed conversion, and egg production in adult Japanese
      quail. Sex differences were examined where possible. 2. GLM analysis was used to
      evaluate the effects of enrichment and housing, while test-retest reliability and
      the stability of measures over 18 d were assessed using partial correlation. 3.
      Foraging enrichment reduced food wastage. 4. Body weight, feed conversion, and
      egg production were not affected by enrichment. Rates of aggressive and feather
      pecking were also not significantly affected, but these behaviours were observed
      very infrequently in this study. 5. Socially-housed birds had poorer feather
      condition, lower body weight and less efficient feed conversion than singly
      housed birds. Social housing did not affect food wastage. 6. There were not sex
      differences in feather pecking, feather condition, food wastage, or feed
      conversion. 7. All measures except feather pecking were reliable over 24 h, but
      only feather condition and body weight were stable over 18 d. The instability f
      the behavioural measures over time suggest that enrichment effects may vary with
      age.

PMID- 17190673
TI  - Genetic parameters for blood oxygen saturation, body weight and breast
      conformation in 4 meat-type chicken lines.
AB  - 1. The objective of the study was to explore the genetic architecture of blood
      oxygen saturation (SaO) (an indicator trait, negatively correlated with ascites
      susceptibility), body weight (Weight) and fleshing score (Flesh, a measure of
      breast conformation) for 4 meat-type chicken lines reared in commercial
      conditions. 2. Genetic components, including heritabilities and genetic
      correlations, were estimated by Restricted Maximum likelihood for these traits
      measured at 6 weeks of age. 3. Data were collected over eight generations of
      selection and pedigrees comprised in excess of 130,000 birds. 4. Univariate
      analyses were performed to allow model definition and to obtain starting values
      for trivariate analyses. The basic model included a random animal effect and, in
      further models explored, a maternal environmental effect or a genetic maternal
      effect or both were fitted. Models were compared using likelihood ratio tests. 5.
      Estimated heritabilities for SaO ranged from 0.1 to 0.2, and there was no
      evidence of genetic maternal effects for SaO. The environmental maternal
      component was significant for one of the populations only. Estimated
      heritabilities for both Weight and Flesh were between 0.2 and 0.4, and there was
      evidence of environmental and genetic maternal effects for these traits in all
      populations. 6. Genetic correlations between SaO and Weight and between SaO and
      Flesh were low and negative. This suggests that, in principle, genetic selection
      to simultaneously increase SaO, and therefore decrease ascites susceptibility,
      and WEight and Flesh could be performed using traditional (marker-free) selection
      methods. We discuss how a putative interaction between ascites and production
      traits could jeopardise the success of such methods.

PMID- 17190674
TI  - Segregation analysis of blood oxygen saturation in broilers suggests a major gene
      influence on ascites.
AB  - 1. Blood oxygen saturation (SaO) is a potential indicator trait for resistance to
      ascites in chickens. 2. The objective of the study was to investigate the genetic
      architecture of SaO in a meat-type chicken line reared in commercial conditions.
      3. Data were collected over 15 generations of selection and were divided into two
      data sets on the basis of a change in recording age from 6 to 5 weeks of age,
      approximately halfway through the period. The resulting pedigrees comprised in
      excess of 90,000 birds each and, on average, 12% of these birds had SaO records.
      4. Segregation analyses of SaO were carried out assuming a mixed inheritance
      model that included a major locus segregating in a polygenic background. 5. The
      analyses suggest that a major gene is involved in the genetic control of SaO in
      this line. The putative gene acts in a dominant fashion and has an additive
      effect of around 0.90 sigma(p), equivalent to a predicted difference in SaO
      between the two homozygous classes of more than 10%. The frequency of the allele
      that increases SaO changed from 0.53 to 0.65 from the first to the second set of
      data, consistent with selection on SaO scores. 6. Using estimated genotype
      probabilities at the putative major locus, we inferred that it acts in an
      overdominant fashion on body weight and fleshing score. If the low SaO allele
      leads to susceptibility to ascites, its combined effects are consistent with it
      being maintained in the population by a balance of natural selection on fitness
      nad artificial selection on growth and carcase traits. 7. Even with selection on
      both SaO and growth traits, the combined genotypic effects would make it
      difficult to remove the unfavourable low-SaO allele by means of traditional
      selection without the use of genetic markers.

PMID- 17190675
TI  - Genetic parameters for a heavy female turkey line: impact of simultaneous
      selection for body weight and total egg number.
AB  - 1. The objective of this study was to investigate the strength of the genetic
      association between growth and reproduction traits in turkeys selected for body
      weight, conformation and egg production. 2. Two distinct populations but derived
      from the same heavy turkey female line and situated in different locations (UK
      and USA), were used to estimate genetic parameters using multivariate REML for
      the following traits: body weight at 14 (BW14), 19 (BW19) and 24 (BW24) weeks of
      age and total egg number (EGG). 3. A Box-Cox transformation was applied to egg
      production data to reduce the impact of non-normality. 4. The heritability
      estimates for each trait for the UK and USA populations, respectively, were: BW14
      0.37 and 0.48; BW19 0.34 and 0.43; BW24 0.28 and 0.43; EGG 0.22 and 0.34. 5. The
      genetic correlation between the body weight at all ages and the total egg
      production was strongly negative, reaching a value of -0.75 for the UK and -0.55
      for the USA population. 6. The comparison of our results with published estimates
      in turkeys suggests that the genetic correlation may get stronger in magnitude
      following selection for increased body weight. 7. This could arise from fixation
      during selection of genes favouring larger weights but with minimal effect on egg
      production, leaving the segregating genetic variation dominated by pleiotropic
      loci with antagonistic effects on the traits. 8. Thus, in order to avoid
      continued selection for body weight reducing egg production to a point where
      natural selection offsets selection gains, alternative selection strategies
      should be considered.

PMID- 17190676
TI  - Prediction of carcase and breast weights and yields in broiler chickens using
      breast volume determined in vivo by real-time ultrasonic measurement.
AB  - 1. The use of in vivo real-time ultrasonic (RTU) to predict breast and carcase
      weights and yields in 103 male broiler chickens was evaluated. Breast area
      (mm(2)), thickness (mm) and volume (cm(3)) were measured by RTU in three
      identified sites. After RTU measurements, the broiler chickens were weighed (live
      weight, LW, g) and slaughtered Carcase and breast weights (g) and physical
      measures of breast area (mm(2)), and thickness (mm) corresponding to the three
      identified sites, and volume (cm(3)) were recorded. 2. The best simple
      correlation between RTU and carcase measurements was obtained for breast volume.
      Breast and carcase weights were well predicted by LW. Furthermore, breast volume
      measured in carcase or by RTU was better in predicting breast weight and breast
      and carcase yields. 3. Multiple regression equations were fitted using LW (g) and
      RTU measurement of breast volume to predict breast and carcase weights and
      yields. The coefficients of determination were 0.52 and 0.65 for breast and
      carcase yields, respectively, and 0.92 and 0.99 for breast and carcase weights,
      respectively.

PMID- 17190677
TI  - Effects of alpha-tocopheryl acetate and beta-carotene dietary supplementation on
      the antioxidant enzymes, TBARS and sensory attributes of turkey meat.
AB  - 1. The aim of the study was to evaluate the effects of alpha-tocopheryl acetate
      (50 mg/kg) and beta-carotene (15 mg/kg) dietary supplementation on the oxidative
      status of raw turkey breast and leg muscles assessed by thiobarbituric acid test
      values, the vitamin E levels and the antioxidant enzyme activities. In parallel,
      a quantitative descriptive sensory analysis was carried out on cooked, stored and
      reheated samples. 2. Vitamin E was present in sufficient quantity to reduce
      oxidation, since iron-induced reactive substances (TBARS) were significantly
      lower in antioxidant-supplemented treatments. The results suggested that the
      presence of beta-carotene in the diet limits the accumulation of alpha-tocopherol
      in turkey muscles. 3. In the present study, there was no conclusive relationship
      between dietary antioxidant supplementation and endogenous antioxidant enzyme
      activities. 4. Sensory evaluation showed that a longer supplementation time and
      dose may be necessary in turkeys to prevent meat from rancidity and warmed-over
      flavour (WOF). Leg pastiness and stringiness were modified by dietary antioxidant
      supplementation, indicating the possible synergism between antioxidants and
      cysteine proteinases in the perception of meat quality. 5. Given the modern
      trends that lead consumers to increase their consumption of poultry meat, it
      would be interesting to evaluate the commercial potential and cost effectiveness
      of routine dietary antioxidant supplementation.

PMID- 17190679
TI  - Effects of dietary supplements of selenium, vitamin E or combinations of the two
      on antibody responses of broilers.
AB  - 1. The effects of selenium and vitamin E supplementation on some immune
      parameters were investigated in broilers. 2. Broiler chicks were fed on maize
      soybean diets with different concentrations of vitamin E (0-200 mg/kg) and
      selenium (0-0.2 mg/kg diet) either alone or in combinations from 1 to 42 d of
      age. 3. Chicks were immunised against Newcastle disease virus (NDV) vaccine at 21
      d of age and haemagglutination inhibition (HI) titres were determined after 10 d.
      4. Chicks receiving supplements of 200 mg vitamin E/kg and 0.2 mg selenium/kg
      produced significantly higher HI antibody titres. This was associated with an
      increased serum concentration of total immunoglobulins and circulatory immune
      complexes. 5. The chicks given 200 mg vitamin E/kg and 0.2 mg selenium/kg had
      significantly heavier spleen and bursa. 6. These results suggested that vitamin E
      and selenium have synergistic effects on immune responses.

PMID- 17190678
TI  - The combined effects of alpha-tocopheryl acetate supplementation and enrofloxacin
      administration on oxidative stability of turkey meat.
AB  - 1. The combined effects of dietary supplementation of vitamin E and enrofloxacin
      administration on the oxidative stability of turkey meat were assessed. 2.
      Enrofloxacin concentrations found in muscles and liver samples from turkeys
      receiving 200 g/kg of alpha-tocopheryl acetate plus 50 mg/kg of enrofloxacin
      without a withdrawal period were higher than those of samples administered with
      50 mg/kg of enrofloxacin alone. Similarly, meat samples from turkeys receiving 50
      mg/kg of enrofloxacin with withdrawal plus 200 mg/kg of alpha-tocopheryl acetate
      showed a significantly lower vitamin E accumulation than meat samples of the
      treatment with enrofloxacin without withdrawal plus vitamin E. 3. The results
      indicated an interaction between the antioxidant and the antibiotic in their
      effects on oxidation susceptibility and the abiotic safety of meat from turkeys
      fed on supplemented diets. A mutual stabilisation of both compounds by reducing
      the effects of free radicals or by affecting the absorption of the compounds is
      suggested.

PMID- 17190680
TI  - Pharmacokinetics of sparfloxacin in broiler chicken.
AB  - 1. The pharmacokinetics of sparfloxacin in broiler chicken was investigated
      following a single intravenous dose of 10 mg/kg and a single oral dose of 20
      mg/kg. The pharmacokinetic parameters (AUC(0-24) or C(max)) were integrated with
      the pharmacodynamic parameter (MIC(90)) to optimize sparfloxacin dosage in
      chicken. 2. The apparent volume of distribution, total body clearance, mean
      residence time and elimination half-life following oral administration were
      2.411/kg, 4.55 ml/min per kg, 10.54 and 5.94 h, respectively. Oral
      bioavailability was 61.7%. 3. Sparfloxacin was found to possess clinically useful
      pharmacokinetic properties. Based on pharmacokinetic/pharmacodynamic integration
      an oral dose of 20 mg/kg sparfloxacin for every 24 h might be recommended for a
      successful clinical effect in chickens.

PMID- 17190681
TI  - Dietary conjugated linoleic acid enhances spleen PPAR-gamma mRNA expression in
      broiler chicks.
AB  - 1. The anti-inflammatory effects of dietary conjugated linoleic acid (CLA) on
      broilers repeatedly challenged with lipopolysaccharide (LPS) were investigated.
      2. Day-old broiler chicks were allotted into three treatment groups and fed on a
      control diet or diets containing 5.0 or 10.0 g CLA/kg diet. Six chicks from each
      treatment were injected with LPS (0.25 mg/kg body weight) at 16, 18 and 20 d of
      age. Splenic cyclooxygenase (COX) and inducible nitric oxide synthase (iNOS)
      activities, and prostaglandin E(2) (PGE(2)) and nitric oxide (NO) production as
      well as peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA
      expression were measured at 21 d of age. 3. Chicks fed 10.0 g CLA/kg diet had
      lower COX activities and PGE(2) production that the controls. Dietary CLA (10.0
      g/kg) did not significantly diminish LPS-induced enhancement of COS-2 activity,
      inhibited the subsequent increase in PGE(2) production. 4. Regulation of COX-1
      activity contributed to the difference in PGE(2) production. 5. CLA did not
      markedly attenuate the increase of iNOS activity and NO production caused by LPS
      challenge. Chicks fed CLA had lower iNOS activity and NO production than the
      controls. 6. Dietary CLA activated splenic PPAR-gamma mRNA expression and
      increased PPAR-gamma mRNA expression after LPS injection. 7. These results
      suggest that dietary CLA has immunomodulatory effects in the spleen by
      restricting basal PGE(2) and NO to lower levels and enhancing PPAR-gamma mRNA
      expression. During the inflammatory response, dietary CLA did not alleviate the
      increase in COX-2 and iNOS activities but enhanced PPAT-gamma mRNA expression.

PMID- 17190682
TI  - Microsomal and cytosolic biotransformation of aflatoxin B1 in four poultry
      species.
AB  - 1. This research evaluated differences in hepatic in vitro metabolism of
      aflatoxin B1 (AFB1) on selected avian species. 2. Microsomal and cytosolic liver
      fractions were obtained from chickens, ducks, quails and turkeys; eight males and
      eight females of each. 3. All microsomes studied produced AFB1-8,9-exo-epoxide
      (AFBO), a metabolite regarded as the active product of AFB1. Turkey microsomes
      produced 1.8 and 3.5 times more AFBO than quails and chickens microsomes,
      respectively. 4. Males from evaluated birds produced more AFBO than females, but
      statistically-significant differences between genders were observed only in ducks
      and turkeys. 5. The cytosolic fraction from all four species produced aflatoxicol
      (AFL). Turkey and duck hepatic cytosol produced more AFL than from quail and
      chickens. 6. It is known that turkeys are very sensitive to AFB1, quails are
      intermediate and chickens are particularly resistant; the differences in AFBO
      production shown in our study may help to explain the difference in vivo
      responses among turkeys, quail and chickens. 7. Moreover, AFL may be related to
      AFB1 toxicity; it was produced in larger amounts by hepatic cytosol from the more
      susceptible species. 8. Because AFBO production by microsomes in ducks was
      relatively low, it is possible that other toxicity mechanisms are involved in
      this highly susceptible species.

PMID- 17190683
TI  - Relationships between genetic, environmental and nutritional factors influencing
      osteoporosis in laying hens.
AB  - 1. The effects upon bone quality of feeding limestone in flour or particulate
      form and housing type (cage or aviary) in lines of hens divergently selected for
      high (H) or low (L) bone strength over 7 generations were investigated. 2. As in
      previous generations, highly significant phenotypic differences between lines
      were observed in all measured bone traits at peak egg production (25 weeks) and
      towards the end of production (56 weeks) in both cage and aviary systems. 3. At
      25 weeks there were no significant effects on bone variables of feeding
      particulate limestone although a significant reduction in osteoclast number was
      observed at this age. By 56 weeks osteoclast numbers were further reduced in hens
      fed particulate limestone and beneficial effects on some bone variables were
      observed in this treatment group. 4. The genotypic and dietary improvements upon
      bone quality were independent and additive at both ages. There were very few
      interactive effects. 5. Hens with the freedom to move in an aviary environment
      during the laying period had improved bone status compared to caged siblings.
      Environmental and genotypic effects were additive. 6. There were no effects of
      line on egg production although H line hens had slightly higher egg production by
      56 weeks. Egg numbers were unaffected by diet. Eggshell thickness and strength
      were unaffected by line but hens fed particulate limestone had thicker- and
      stronger-shelled eggs over the production period as a whole. 7. We conclude that;
      (a) genetic selection is extremely effective in improving bone strength and
      resistance to osteoporosis; (b) allowing hens freedom to exercise can also
      improve bone strength but may increase the risk of keel damage if they do not
      have genetically-improved bone status; (c) feeding hens a particulate form of
      limestone from 15 weeks onwards can also increase bone strength and eggshell
      quality; (d) genetics, environment and nutrition all have independent and
      additive effects on bone status in laying hens but the relative effectiveness of
      these factors is genetics > environment > nutrition.

PMID- 17190684
TI  - Echocardiographic characteristics of chickens with ascites syndrome.
AB  - 1. B- and M-mode echocardiography was used to compare cardiac function in
      broilers with spontaneous ascites syndrome with that of normal chickens. 2.
      Thirty ascitic chickens and 15 normal chickens aged three, 4, 5, and 6 weeks from
      the same flock (180 birds in total) were examined. They were restrained gently in
      a natural standing position, and echocardiographs were obtained from a 7.0-MHz
      linear transducer placed on the left pectoral apterium. Indices of cardiac
      structure and functioning were calculated from the echocardiographs, and some
      were normalised to body weight. Heart rate was also measured. 3. All cardiac
      structural indices in both ascitic and normal chickens increased with age.
      Compared with normal chickens, right ventricular diameter at the end of systole
      in ascitic chickens was greater at 4, 5 and 6 weeks of age. Ventricular septal
      thickness at the end of both systole and diastole was greater in ascitic chickens
      at 5 and 6 weeks. Left ventricular free wall thickness at the end of diastole was
      less in ascitic chickens at 3 weeks. However, all the structural indices
      decreased with age after normalisation with body weight. 4. The heart rate of
      ascitic chickens was lower at 4, 5 and 6 weeks. Normalised left ventricular
      fractional shortening was lower in ascitic chickens at 4, 5 and 6 weeks, as was
      normalised right ventricular fractional shortening. Incrassation of the
      ventricular septum (Delta T), which changed little in normal chickens, was less
      at 4, 5 and 6 weeks in ascitic chickens. Left ventricular fractional shortening,
      right ventricular fractional shortening and Delta T were all negatively
      correlated with ascites heart index at all ages. 5. Taken together the results
      suggest heart failure of both ventricle, but that right ventricular dysfunction
      is more extensive than left ventricular dysfunction. We suggest that secondary
      pulmonary hypertension would result in these ascitic chickens due to volume
      overload.

PMID- 17190685
TI  - Methods of sonographic cervical length measurement in pregnancy: a review of the
      literature.
AB  - In this review we give an overview of the methods and pitfalls in cervical length
      measurements. We compared the different techniques and investigated factors that
      influence visualization of the cervix. The data in this overview may be used to
      establish guidelines in clinical practice.

PMID- 17190686
TI  - Mechanisms of progesterone action in inhibiting prematurity.
AB  - Progesterone is a steroid hormone that plays an integral role in each step of
      human pregnancy. In early pregnancy, progesterone produced by the corpus luteum
      is critical to the maintenance of early pregnancy until the placenta takes over
      this function at 7 to 9 weeks of gestation, hence its name (pro-gestational
      steroid hormone). The role of progesterone in later pregnancy, however, is less
      clear. It has been proposed that progesterone may be important in maintaining
      uterine quiescence in the latter half of pregnancy by limiting the production of
      stimulatory prostaglandins and inhabiting the expression of contraction
      associated protein genes within the myometrium. Although systemic progesterone
      withdrawl may not correlate directly with the onset of labour in humans, there is
      increasing evidence to suggest that progesterone exerts its influence indirectly
      via a 'functional' withdrawl at the level of the uterus. The molecular mechanisms
      by which progesterone is able to maintain uterine quiescence and prevent preterm
      birth in some high-risk women are not clear. Six putative mechanisms have been
      proposed in the literature by both US and other investigators and are explored in
      this review.

PMID- 17190687
TI  - Epidemiology of preterm birth and its clinical subtypes.
AB  - Preterm birth (<37 weeks) complicates 12.5% of all deliveries in the USA, and
      remains the leading cause of perinatal mortality and morbidity, accounting for as
      many as 75% of perinatal deaths. Despite the recent temporal increase in preterm
      birth, efforts to understand the problem of prematurity have met with little
      success. This may be attributable to the under-appreciation of the etiologic
      heterogeneity of preterm birth as well as the heterogeneity in its underlying
      clinical presentations--spontaneous onset of labor, preterm premature rupture of
      membranes, and medically indicated preterm birth. In this paper, we review data
      regarding preterm births with particular focus on its incidence, temporal trends,
      and recurrence. Studies of births from the USA indicate that the recent temporal
      increase in the overall preterm birth rate is driven by an impressive concomitant
      increase in medically indicated preterm birth. However, the largest temporal
      decline in perinatal mortality has also occurred among medically indicated
      preterm births (relative to other clinical subtypes), suggesting that these
      obstetric interventions at preterm gestational ages are associated with a
      reduction in perinatal mortality. Recent data indicate that spontaneous preterm
      birth is not only associated with increased recurrence of spontaneous, but also
      medically indicated, preterm birth, and vice versa. This suggests that the
      clinical subtypes may share common underlying etiologies. Since medically
      indicated preterm birth accounts for as many as 40% of all preterm births,
      efforts to understand the reasons for such interventions and their impact on
      short- and long-term morbidity in newborns is compelling. Further research is
      necessary in order to understand the mechanisms and etiology of preterm birth,
      thus leading to the possibility of effective preventive or therapeutic
      strategies.

PMID- 17190688
TI  - Prevention of PPROM: current and future strategies.
AB  - Our understanding of the pathophysiologic processes leading to preterm premature
      rupture of membranes (PPROM) has grown tremendously in recent years. Evidence
      suggests that there may be a genetic susceptibility to PPROM and that genetic and
      environmental elements are important cofactors in its development. A number of
      risk-based protocols have been proposed in an attempt to identify those women at
      highest risk for PPROM. While we have made advances in the area of predicting
      PPROM, treatments based on current risk-based systems have failed to distinguish
      a specific, effective preventive therapy for PPROM. The concept that genetic
      factors increase susceptibility or decrease resistance to disease has stimulated
      new work in the field of PPROM. Several maternal and fetal gene polymorphisms
      have been identified that are associated with an increased risk for PPROM.
      Patients with 'susceptible' genotypes may also have clinical risk factors for
      PPROM resulting in a synergistic increase in the risk for PPROM, a so-called gene
      environment interaction. The concept that these gene-environment interactions
      represent new targets for our efforts to prevent PPROM is explored.

PMID- 17190689
TI  - The 80-hour workweek restriction: How are OB/GYN resident procedure numbers
      affected?
AB  - OBJECTIVE: To evaluate the surgical caseload in a military obstetrics and
      gynecology residency program, prior to and after implementation of an 80-hour
      workweek. METHODS: A retrospective cohort study evaluating data submitted to the
      Accreditation Council for Graduate Medical Education (ACGME) for cumulative
      resident procedures in obstetrics and gynecology for the years before (July 2001
      June 2002) and after (July 2002-June 2003) 80-hour workweek implementation. Total
      obstetric and gynecology procedures were examined using both the Student's paired
      t-test and a two-way mixed factor analysis of variance. RESULTS: Between July
      2001 and June 2002 there were 822 gynecological cases and 3958 deliveries done by
      17 OB/GYN residents; these were compared with 827 cases and 3504 deliveries done
      by 18 OB/GYN residents between July 2002 and June 2003 (p=0.189). The total
      numbers of obstetric and gynecology cases pre- and post-80-hour workweek
      intervention were similar when evaluated by month (July through June of 2001/2
      vs. 2002/3; p=0.908). There was a significantly greater number of obstetrics
      cases compared with gynecological cases (p < 0.001) in the pre- vs. post-80-hour
      workweek groups; the number of gynecological cases remained constant in the post
      80-hour workweek group while the obstetric numbers dropped (p=0.001). CONCLUSION:
      The 80-hour workweek restriction resulted in similar total numbers of obstetrics
      and gynecology cases, although the total number of obstetric cases per resident
      declined after implementation.

PMID- 17190690
TI  - Renal impairment associated with indomethacin treatment for patent ductus
      arteriosus in extremely preterm neonates--is postnatal age at start of treatment
      important?
AB  - OBJECTIVE: To study serum creatinine (SCr) levels following indomethacin for
      patent ductus arteriosus (PDA) closure in extremely preterm neonates in relation
      to postnatal age at the start of treatment. METHODS: This was a retrospective
      (January 2000-December 2002) analysis of data on preterm neonates (gestation <29
      weeks) who received indomethacin for PDA. Pre-existing renal malformation and/or
      impairment and high serum levels of nephrotoxic drugs were criteria for
      exclusion. RESULTS: Indomethacin was commenced at postnatal age <7 days and >or=7
      days in 60 (group 1) and 30 (group 2) neonates, respectively. The median (Q1, Q3)
      gestational age and birth weight for group 1 and group 2 neonates were 25 (23,
      27) vs. 25 (24, 26) weeks and 740 (620, 909) vs. 780 (663, 966) grams,
      respectively. Postnatal age <7 days at start of indomethacin was associated with
      higher baseline (0.083 (0.074, 0.090) vs. 0.073 (0.054, 0.083) mmol/L, p=0.001)
      and peak SCr levels (0.099 (0.089,0.109) vs. 0.090 (0.064, 0.104) mmol/L,
      p=0.015). Logistic regression analysis controlling for gestational age and
      baseline SCr level indicated that postnatal age >or=7 days was a risk factor for
      elevated SCr after indomethacin (OR=13.4, 95% CI: 3.8-46.6, p < 0.001).
      CONCLUSION: Postnatal age >or=7 days at the start of indomethacin is a predictor
      of a significant rise in SCr in extremely preterm neonates.

PMID- 17190691
TI  - Prediction of intrauterine pressure waveform from transabdominal
      electrohysterography.
AB  - OBJECTIVE: We investigated the ability to non-invasively obtain uterine
      electromyograms (EMG; electrohysterogram (EHG)) to predict the intrauterine
      pressure (IUP) waveform. STUDY DESIGN: Patients enrolled in a term labor study of
      trans-abdominal electrical activity, who underwent IUP monitoring for obstetric
      indication, were included in this study (n=14). EHG signals were processed and
      prediction filters trained against the IUP from the same patient. Sixty-eight 10
      minute traces each of EHG and IUP waveforms were reviewed (Montevideo unit (MVU)
      calculation) by two experienced labor nurses and one obstetrician, blinded to
      patient and EHG vs. IUP output. In addition, area under the contraction curve
      (AUC), contraction detection and duration were compared. RESULTS: EHG-derived
      MVUs statistically correlated with IUP (r=0.795; p < 0.0001), but mathematically
      differed by 17+/-20% with 83% of EHG MVUs underestimating the IUP. The
      coefficients of variation between the two methods were relatively high (
      approximately 20%), and these could not be substantially corrected via
      calibration. AUC differed by 8+/-19% with 69% of EHG-derived AUC underestimating
      the IUP. EHG detected 98% of 362 IUP contractions, with 8% over-detection.
      Contraction duration was similar: 56.4+/-11.9 s vs. 55.7+/-13.0 s, for IUP and
      EHG, respectively. CONCLUSION: EHG-based contraction monitoring approximates IUP
      monitoring for contraction detection and duration. The correlation with
      contraction height (MVU) and AUC is much weaker with the investigated signal
      processing algorithm.

PMID- 17190692
TI  - Transient hyperthyroxinemia in newborns from women with autoimmune thyroid
      disease and raised levels of thyroid peroxidase antibodies.
AB  - OBJECTIVE: Although it is well established that maternal thyroid disease and
      increased levels of thyrotropin receptor antibodies (TRab) during pregnancy are
      associated with a number of complications, is the significance of increased
      levels of thyroid peroxidase antibodies (TPOab) alone a matter for discussion?
      The aim of the present study was to examine whether transplacental passage of
      TPOab from women with autoimmune thyroid disease (AITD) interferes with thyroid
      function in the neonate. METHODS: Pregnant women with AITD (raised levels of
      TPOab) and their neonates were monitored with regard to variations of thyroid
      hormones, thyrotropin (TSH), and TPOab. Pregnant women with non-AITD served as
      controls. RESULTS: The neonates from mothers with AITD, independently of the
      presence also of TRab in the mothers, had a transient hyperthyroxinemia one week
      following birth. Neonatal TPOab correlated with that of the mothers at gestation
      and was cleared concomitantly with normalization of thyroxine. A high frequency
      (21%) of severe hyperbilirubinemia was observed in neonates from mothers with
      AITD. CONCLUSION: Children of mothers with raised levels of TPOab, have a
      transient hyperthyroxinemia one week after birth accompanied by a high frequency
      of hyperbilirubinemia suggesting that clinical examination and blood testing
      should be performed consecutively during the first postnatal week.

PMID- 17190693
TI  - Multiplanar three-dimensional prenatal aided diagnosis of Arnold-Chiari type 2
      malformation: comparison between 2D and 3D ultrasound.

PMID- 17190694
TI  - Use of middle cerebral artery peak systolic velocity and intrauterine transfusion
      for management of twin-twin transfusion and single fetal intrauterine demise.

PMID- 17190695
TI  - Complete hydatidiform mole and coexisting healthy twin: a rare case of a benign
      form.

PMID- 17190696
TI  - Ethics, standards, and procedures of animal and human chronobiology research.
AB  - The majority of research papers published in Chronobiology International report
      the findings of investigations conducted on laboratory animals and human beings.
      The editors and the readers of the journal expect the authors of submitted
      manuscripts to have made an important contribution to biological rhythm and
      related research through the ethical conduct of investigations and unbiased and
      accurate reporting of findings. Authors of scientific papers are required to
      disclose any potential conflict of interest. The journal accepts only papers that
      are original work, no part of which has been submitted for publication elsewhere,
      except as brief abstracts. The journal and its editors endorse the compliance of
      investigators to the principles of the Declaration of Helsinki of the World
      Medical Association, which relate to the conduct of ethical research on human
      beings, and the Guide for the Care and Use of Laboratory Animals of the Institute
      for Laboratory Animal Research of the National Research Council, which relate to
      the conduct of ethical research on laboratory and other animals. The peer review
      of manuscripts by Chronobiology International thus includes judgment as to
      whether or not the investigative methods conform to the standards of good
      research practice. This article updates the ethical policies, standards, and
      procedures for manuscripts submitted to Chronobiology International that involve
      human and animal biological rhythm research, both from the perspective of the
      criteria of quality chronobiology investigation and from the perspective of
      humane and ethical research on human beings and animals.

PMID- 17190697
TI  - Vital working hour schemes: The dynamic balance between various interests.
AB  - "Balancing Interests", the theme of the 17th International Symposium on Shift
      Work and Working Time held in Hoofddorp, The Netherlands (September 2005), refers
      to the ambition to reach an optimal balance between the various aspects of shift
      work. Economic, ergonomic, physical, and psychosocial factors all interact in
      determining the impact of shift work at the individual, organizational, and
      societal level. It is the challenge of this multidisciplinary field of research
      to model all relevant factors in such a way that it will allow us to optimize the
      dynamic trade-off between the yield and the risk of shift work. The organizers of
      the 17th International Symposium and the co-editors of these proceedings are
      convinced that the high quality of the contributions will bring us closer to this
      ultimate goal.

PMID- 17190698
TI  - Smoking among shift workers: More than a confounding factor.
AB  - In studies on the cardiovascular disease risk among shift workers, smoking is
      considered to be a confounding factor. In a study of 239 shift and 157 daytime
      workers, it was found that shift work was prospectively related to increased
      cigarette consumption, indicating that smoking might be in the causative pathway;
      however, the number of study subjects was too low to warrant sound conclusions.
      Therefore, data from the Maastricht Cohort study were used to investigate the
      longitudinal relation between smoking and shift work in a much larger population.
      In this study, a total of 12,140 employees were followed for two years by means
      of self-administered questionnaires. The authors compared workers who normally
      worked during daytime hours only (74%) with those who worked other than day
      shifts (26%). Logistic regression analyses were performed, adjusting for
      demographic factors of age, gender, and educational level to evaluate the risk of
      starting to smoke (n = 25) in the group of non-smoking workers and the risk of
      quitting (n = 318) in the group of smoking workers. Logistic regression analysis
      showed a significant association between shift work and taking up smoking during
      the two-year follow-up (odds ratio: 1.46, p = 0.03). The risk to stop smoking was
      somewhat lower in shift workers (odds ratio: 0.91) but not statistically
      significant (p = 0.5). To conclude, this study showed that, independent of
      educational level, shift workers are more prone to start smoking. This finding
      might have important implications for studies on the health effects of shift
      workers and for possible interventions aimed at the reduction of the excess
      health risk among shift workers.

PMID- 17190699
TI  - Recovery after shift work: Relation to coronary risk factors in women.
AB  - Shift work increases the risk for developing cardiovascular disease. There is,
      however, little knowledge of what aspects of shift scheduling that are
      detrimental and what characteristics promote good health. The aim of the present
      study was to evaluate whether coronary risk factors deteriorate after a hard work
      period and whether recovery, in the form of a week off, was sufficient to improve
      them. A total of 19 women worked an extremely rapidly rotating and clockwise
      shift schedule at a paper and pulp factory. They underwent two health
      examinations, one at the end of the work period and one after the week off. In
      addition, the women were divided into a tolerant and a vulnerable group,
      depending on their satisfaction with their work hours. Most risk factors did not
      change, but total cholesterol and low-density lipoprotein (LDL)-cholesterol were
      lower after the working period than after the week-off. In addition, vulnerable
      women had higher levels of total cholesterol and a higher ratio of total
      cholesterol/high-density lipoprotein (HDL) than tolerant ones. In conclusion, the
      finding that a week-off worsens cholesterol levels was against our hypothesis and
      suggests further studies on how activities/responsibilities outside the workplace
      affect shift-working women. It was also shown that susceptible shift workers had
      worse lipid profiles.

PMID- 17190700
TI  - Influence of flexibility and variability of working hours on health and well
      being.
AB  - Flexible working hours can have several meanings and can be arranged in a number
      of ways to suit the worker and/or employer. Two aspects of "flexible" arrangement
      of working hours were considered: one more subjected to company control and
      decision (variability) and one more connected to individual discretion and
      autonomy (flexibility). The aim of the study was to analyze these two dimensions
      in relation to health and well-being, taking into consideration the interaction
      with some relevant background variables related to demographics plus working and
      social conditions. The dataset of the Third European Survey on working
      conditions, conducted in 2000 and involving 21,505 workers, was used. Nineteen
      health disorders and four psycho-social conditions were tested by means of
      multiple logistic regression analysis, in which mutually adjusted odds ratios
      were calculated for age, gender, marital status, number of children, occupation,
      mode of employment, shift work, night work, time pressure, mental and physical
      workload, job satisfaction, and participation in work organization. The
      flexibility and variability of working hours appeared inversely related to health
      and psycho-social well-being: the most favorable effects were associated with
      higher flexibility and lower variability. The analysis of the interactions with
      the twelve intervening variables showed that physical work, age, and flexibility
      are the three most important factors affecting health and well-being. Flexibility
      resulted as the most important factor to influence work satisfaction; the second
      to affect family and social commitment and the ability to do the same job when 60
      years old, as well as trauma, overall fatigue, irritability, and headache; and
      the third to influence heart disease, stomachache, anxiety, injury, and the
      feeling that health being at risk because of work. Variability was the third most
      important factor influencing family and social commitments. Moreover, shift and
      night work confirmed to have a significant influence on sleep, digestive and
      cardiovascular troubles, as well and health and safety at work. Time pressure
      also showed a relevant influence, both on individual stress and social life.
      Therefore, suitable arrangements of flexible working time, aimed at supporting
      workers' coping strategies, appear to have a clear beneficial effect on worker
      health and well-being, with positive consequences also at the company and social
      level, as evidenced by the higher "feeling to be able to work until 60 years of
      age".

PMID- 17190701
TI  - Shift work and inter-individual differences in sleep and sleepiness.
AB  - Inter-individual differences in tolerance for shift work have been studied
      primarily in terms of external factors affecting alertness on the job or the
      ability to rest and sleep while at home. However, there is increasing evidence
      that neurobiological factors play a role as well, particularly the major
      processes involved in the regulation of sleep and wakefulness. These include a
      sleep homeostatic process seeking to balance wakefulness and sleep and a
      circadian process seeking to promote wakefulness during the day and sleep during
      the night. Shift work is associated with a temporal misalignment of these two
      endogenous processes. During nightwork, this misalignment makes it difficult to
      stay awake during the nightshift and sleep during the day. However, inter
      individual variability in the processes involved in sleep/wake regulation is
      substantial. Recent studies have demonstrated the existence of inter-individual
      differences in vulnerability to cognitive deficits from sleep loss. Moreover,
      these inter-individual differences were shown to constitute a trait.
      Interestingly, self-evaluations of sleepiness did not correspond well with the
      trait inter-individual variability in objective levels of performance impairment
      during sleep deprivation. Perhaps because of this discrepancy, in operational
      settings, the inter-individual differences in vulnerability to sleep loss do not
      appear to be limited due to self-selection mechanisms. Indeed, even among a
      highly select group of active-duty jet fighter pilots flying a series of
      simulated night missions, systematic inter-individual differences in performance
      impairment from sleep loss were still observed. There are significant personal
      and economic consequences to human error and accidents caused by performance
      deficits due to sleep loss. It is important, therefore, to study the inter
      individual differences in the regulation of sleep and wakefulness in the work
      environment so that cognitive impairment during shift work may be better
      anticipated and prevented.

PMID- 17190702
TI  - A pilot study of the safety implications of Australian nurses' sleep and work
      hours.
AB  - The frequency and severity of adverse events in Australian healthcare is under
      increasing scrutiny. A recent state government report identified 31 events
      involving "death or serious [patient] harm" and 452 "very high risk" incidents.
      Australia-wide, a previous study identified 2,324 adverse medical events (AME) in
      a single year, with more than half considered preventable. Despite the recognized
      link between fatigue and error in other industries, to date, few studies of
      medical errors have assessed the fatigue of the healthcare professionals
      involved. Nurses work extended and unpredictable hours with a lack of regular
      breaks and are therefore likely to experience elevated fatigue. Currently, there
      is very little available information on Australian nurses' sleep or fatigue
      levels, nor is there any information about whether this affects their
      performance. This study therefore aims to examine work hours, sleep, fatigue and
      error occurrence in Australian nurses. Using logbooks, 23 full-time nurses in a
      metropolitan hospital completed daily recordings for one month (644 days, 377
      shifts) of their scheduled and actual work hours, sleep length and quality,
      sleepiness, and fatigue levels. Frequency and type of nursing errors, near
      errors, and observed errors (made by others) were recorded. Nurses reported
      struggling to remain awake during 36% of shifts. Moderate to high levels of
      stress, physical exhaustion, and mental exhaustion were reported on 23%, 40%, and
      36% of shifts, respectively. Extreme drowsiness while driving or cycling home was
      reported on 45 occasions (11.5%), with three reports of near accidents. Overall,
      20 errors, 13 near errors, and 22 observed errors were reported. The perceived
      potential consequences for the majority of errors were minor; however, 11 errors
      were associated with moderate and four with potentially severe consequences.
      Nurses reported that they had trouble falling asleep on 26.8% of days, had
      frequent arousals on 34.0% of days, and that work-related concerns were either
      partially or fully responsible for their sleep disruption on 12.5% of occasions.
      Fourteen out of the 23 nurses reported using a sleep aid. The most commonly
      reported sleep aids were prescription medications (62.7%), followed by alcohol
      (26.9%). Total sleep duration was significantly shorter on workdays than days off
      (p < 0.01). In comparison to other workdays, sleep was significantly shorter on
      days when an error (p < 0.05) or a near error (p < 0.01) was recorded. In
      contrast, sleep was higher on workdays when someone else's error was recorded (p
      = 0.08). Logistic regression analysis indicated that sleep duration was a
      significant predictor of error occurrence (chi2 = 6.739, p = 0.009, e beta =
      0.727). The findings of this pilot study suggest that Australian nurses
      experience sleepiness and related physical symptoms at work and during their trip
      home. Further, a measurable number of errors occur of various types and severity.
      Less sleep may lead to the increased likelihood of making an error, and
      importantly, the decreased likelihood of catching someone else's error. These
      pilot results suggest that further investigation into the effects of sleep loss
      in nursing may be necessary for patient safety from an individual nurse
      perspective and from a healthcare team perspective.

PMID- 17190703
TI  - Work ability of health care shift workers: What matters?
AB  - This paper aims at identifying variables associated with inadequate work ability
      among nursing personnel at a public hospital, considering factors related to
      socio-demographic, lifestyles, working conditions, and health outcomes. A cross
      sectional study was conducted in a university hospital in Sao Paulo, Brazil, as
      part of a larger research study on tolerance to 12 h night work. Nursing staff
      included registered nurses, nurse technicians, and nurse aides; in total, there
      were 996 healthcare workers (878 female; 118 male) at the time of the study. Some
      696 workers (69.9%) of the population agreed to participate. Data collection
      (October 2004-July 2005) was based on a comprehensive questionnaire about living
      and working conditions (including incivility at work, work demands, work control,
      and support), mental and physical health symptoms (fatigue and sleep problems),
      and work ability. This report presents analyses of the adapted Brazilian version
      of the Work Ability Index (WAI) and associated variables. The study population
      worked one of the following shift schedules at this hospital: 12 h nights
      followed by 36 h off or 9 h or 6 h day (morning or afternoon) shifts. The mean
      age of the respondents was 34.9 (S.D.+/-10.4) years of age; 31.5% of the
      participants held two jobs. Statistical analyses using a hierarchical multiple
      logistic regression model were performed to evaluate the factors associated with
      inadequate (moderate and low scores) of the WAI. The significantly associated
      factors were socio-demographic (income responsibility, sole breadwinner, raising
      kids, age group), working conditions (thermal discomfort, organization of the
      workplace, and verbal abuse), and health outcomes (high body mass index, obesity,
      sleep problems, and fatigue). In spite of limitations of the study design,
      results indicate that the nursing profession is associated with stressful working
      conditions, contributing to inadequate WAI. This is in addition to bad living
      conditions and precarious work. Intervention measures, either at the workplace or
      at individual levels, are necessary to prevent a decrease in work ability, even
      in this quite young working population.

PMID- 17190704
TI  - Estimating the circadian rhythm in the risk of occupational injuries and
      accidents.
AB  - The authors recently published a prototypic Risk Index (RI) to estimate the risk
      of critical errors associated with shift systems. This RI was based on published
      trends in the relative risk of injuries and accidents, and a simple additive
      model was proposed to estimate the risk for a given shift system. However,
      extending the RI to irregular work schedules requires an estimation of the phase
      and amplitude of the circadian rhythm in risk. This paper integrates the
      published evidence on three independent sources of data that allow such
      estimations to be made: the trend in risk over a 24 h day, over the course of the
      night shift, and across the three different (8 h) shifts. Despite potential
      confounders, maximum risk (i.e., acrophase = peak time) estimates across these
      three trends showed a remarkable consistency, with all three estimates occurring
      at about midnight, although the amplitude estimates varied considerably. The best
      estimate of the amplitude of the circadian rhythm in risk would appear to be that
      based on trend over the three (8 h) shifts, as this trend is the least
      confounded. The estimated acrophase (peak time) in risk appeared earlier than
      would be predicted from consideration of the circadian rhythm in alertness,
      fatigue, or performance on simple interpolated tasks, such as reaction time or
      performance on the Psychomotor Vigilance Test.

PMID- 17190705
TI  - Sleepiness and sleep in a simulated "six hours on/six hours off" sea watch
      system.
AB  - Ships are operated around the clock using rapidly rotating shift schedules called
      sea watch systems. Sea watch systems may cause fatigue, in the same way as other
      irregular working time arrangements. The present study investigated subjective
      sleepiness and sleep duration in connection with a 6 h on/6 h off duty system.
      The study was performed in a bridge simulator, very similar to those found on
      ships. Twelve officers divided into two groups participated in the study that
      lasted 66 h. Half of the subjects started with the 06:00-12:00 h watch and the
      other half with the 12:00-18:00 h watch. The subjects alternated between off-duty
      and on-duty for the remainder of the experimental period. Approximately halfway
      through the experiment, the 12:00-18:00 h watch was divided into two 3 h
      watches/off-duty periods. The effect of this was to reverse the on-duty/off-duty
      pattern between the two groups. This enabled all subjects to work the four
      possible watches (00:00-06:00 h, 06:00-12:00 h, 12:00-18:00 h, and 18:00-24:00 h)
      in an order that was essentially counterbalanced between groups. Ratings of
      sleepiness (Karolinska Sleepiness Scale; KSS) were obtained every 30 min during
      on-duty periods and if subjects were awake during off-duty periods. The
      subjectively rated duration of sleep was recorded after each off-duty period that
      preceded watch periods when KSS was rated. The results showed that the average
      level of sleepiness was significantly higher during the 00:00-06:00 h watch
      compared to the 12:00-18:00 h and 18:00-24:00 h watches, but not to the 06:00
      12:00 h watch. Sleepiness also progressed significantly from the start toward the
      end of each watch, with the exception of the 06:00-12:00 h watch, when levels
      remained approximately stable. There were no differences between groups (i.e.,
      the order between watches). Sleep duration during the 06:00-12:00 h off-duty
      period (3 h 29 min) was significantly longer than during the 12:00-18:00 h period
      (1 h 47 min) and the 18:00-24:00 h period (2 h 7 min). Sleep during the 00:00
      06:00 h period (4 h 23 min) was longer than all sleep periods except the 06:00
      12:00 h period. There were no differences between groups. In spite of sufficient
      opportunities for sleep, sleep was on the average around 1-1 h 30 min shorter
      than the 7-7 h 30 min that is considered "normal" during a 24 h period. This is
      probably a consequence of the difficulty to sleep during daytime due to the
      alerting effects of the circadian rhythm. Also, sleepiness during the night and
      early mornings reached high levels, which may be explained by a combination of
      working close to or during the circadian trough of alertness and the relatively
      short sleep periods obtained. An initial suppression of sleepiness was observed
      during all watches, except for the 06:00-12:00 h watch. This suppression may be
      explained by the "masking effect" exerted by the relative high levels of activity
      required when taking over the responsibility of the ship. Toward the end of
      watches, the levels of sleepiness progressively increased to relatively high
      levels, at least during the 00:00-06:00 h watch. Presumably, initially high
      levels of activity are replaced by routine and even boredom.

PMID- 17190706
TI  - Diurnal urinary 6-sulfatoxymelatonin levels among healthy Danish nurses during
      work and leisure time.
AB  - The present study aims to examine the influence of evening and night shift work,
      compared to day shift work, on melatonin secretion in nurses in a field setting.
      Effects were examined during a workday and during a day off. Both fixed schedules
      and mixed or rotating schedules were studied. In total, 170 nurses were studied:
      89 nurses worked fixed schedules, 27 nurses worked the day shift, 12 nurses
      worked the evening shift, 50 nurses worked the night shift, and 82 nurses worked
      mixed schedules, with data collected during a day (n = 17), evening (n = 14), or
      night shift (n = 50). All spot urine samples were collected during 24 h from the
      participants on a work day and on a day off and were analyzed for 6
      sulphatoxymelatonin. On the day of urine sampling, participants filled in the
      Karolinska Sleep Diary. Additional information was collected through a telephone
      interview. Data were analyzed using a mixed procedure with autoregressive
      covariance structure. The present study showed that shift work affected the
      concentrations of 6-sulphatoxymelatonin in the short term by lower excretion in
      urine from nurses working the night compared to day shift on a workday and on a
      day off as well. No significant differences were observed between a workday and a
      day off when doing day and evening shifts, irrespective of mixed and fixed
      schedules. Sleep length was reduced workdays (from 6.1-6.8 h) among all nurses,
      compared to days off (from 7.8-8.7 h).

PMID- 17190707
TI  - Are individuals' nighttime sleep characteristics prior to shift-work exposure
      predictive for parameters of daytime sleep after commencing shift work?
AB  - This study aimed to examine prospectively whether individual nighttime sleep
      characteristics at baseline (prior to shift-work exposure) are related to
      parameters of daytime sleep after commencing shift work. A longitudinal field
      study was carried out with novice police officers of the Dutch Police Force. A
      total of 26 subjects were examined at baseline before they entered shift work and
      re-examined during follow-up sessions after four and twelve months of shift-work
      exposure. Wrist actigraphy and sleep diaries were used to study nocturnal sleep
      at baseline and daytime sleep after night shifts during follow-up sessions. As
      outcome variables, estimated total sleep time, sleep efficiency, and subjective
      sleep quality were analyzed. Daytime total sleep time showed a 66 min decline
      during the first year of shift-work exposure. Systematic inter-individual
      differences were observed for daytime total sleep time and subjective sleep
      quality (explaining 53% and 38% of the variance, respectively), suggesting
      potential predictability of these sleep parameters. Although no predictors were
      found for daytime total sleep time, the subjective quality of nighttime sleep
      before the onset of shift work predicted 40% of the variance in the subjective
      quality of daytime sleep after commencing shift work. Follow-up studies may
      reveal whether the subjective quality of baseline nighttime sleep also predicts
      long-term overall tolerance for shift work.

PMID- 17190708
TI  - Ultradian and asymmetric rhythms of hemispheric processing speed.
AB  - Daily changes in cognitive performance have been documented, both in time of
      day/effect paradigm studies and in time-isolation studies. However, in both types
      of studies, phenomena such as the "post-lunch dip" have been found that were
      difficult to explain in terms of theoretical backgrounds. These phenomena may
      suggest ultradian rhythms in cognitive performance. A number of studies have also
      shown ultradian and asymmetric rhythms in activity indices of the brain
      hemispheres. The aim of this study was to test three hypotheses: the first two
      assumed that there is a significant ultradian frequency in a component of the
      endogenous rhythm of processing speed, and the third assumed that the ultradian
      endogenous rhythms of the processing speed (encoding and recognition) of stimuli
      addressed to the left brain hemisphere differ in period length from those
      addressed to right hemisphere. During a 24 h constant-routine experiment, the
      memory performance of 30 participants was measured eight times (every 2.5-3 h),
      starting at 06:30 h. Parallel sets of words and pictures were shown to subjects
      in a random order in either the left or the right visual field on a computer
      screen. The participants pressed one of two buttons in response to the picture or
      word, or when answering a question concerning the meaning of a presented
      stimulus. Cosinor analysis was applied to individual time series data. Two
      significant ultradian components were found in a majority of the time series.
      Dominant periods were analyzed using three factor ANOVA. The results showed an
      asymmetry between both hemispheres in the frequency of ultradian rhythms in
      encoding speed.

PMID- 17190709
TI  - Train drivers' sleep quality and quantity during extended relay operations.
AB  - Relay operations are an important mode of freight transportation within
      Australia. Relay work requires multiple crews to drive the train continuously
      from one specified destination to another and return. Importantly, the nature of
      relay work requires train drivers to sleep on-board during designated resting
      shifts. The main aim of the present study was to investigate the quality and
      quantity of sleep obtained in on-board rest facilities (relay vans) during
      extended (four-day) relay operations. Drivers (n = 9) working the Port Augusta to
      Darwin relay operation volunteered to participate. The first leg of the trip
      typically took 40 h followed by an overnight stay in Darwin (between 8-12 h)
      prior to return. Two crews, each consisting of two drivers, changed every 8 h,
      giving the crew an 8 h rest in the relay van prior to each 8 h working shift.
      Using polysomnography, home sleep data were collected prior to and following each
      trip using a standard five-channel EEG montage. All sleep periods during the
      relay trip (including Darwin) were also recorded. Additionally, subjective sleep
      quality ratings were recorded following each sleep period. Analyses revealed that
      the quantity of sleep obtained in the relay vans (3.3 h) was significantly
      reduced compared to home (6.8 h). In general, the total sleep time was increased
      at night and reduced during the day. In terms of quality, sleep onset latency,
      sleep efficiency, and amount of slow wave and rapid eye movement sleep did not
      differ significantly between home and the relay vans. The results of the study
      highlight sleep quantity as the main concern during extended relay operations.
      Future research should focus on investigating the subjective and objective impact
      of this sleep reduction on waking functions.

PMID- 17190710
TI  - Self-awareness of impairment and the decision to drive after an extended period
      of wakefulness.
AB  - Fatigue is an increasingly noted factor in road accidents. The ability to predict
      and be aware of impairment in terms of driving capability is important for
      potential legal liability and road safety. However, to date, there have been few
      studies that have investigated the accuracy of individuals in predicting how
      safely they could drive during conditions of sleep loss. Research has
      demonstrated that individuals rate themselves as better than the population
      average in a number of domains, including driving-related skills. Therefore, this
      study also aimed to investigate self-ratings of predicted driving ability during
      extended wakefulness and compare them to ratings made of a hypothetical other
      person under the same conditions. Thirty-two participants remained awake for a
      period of 40 h. Every 2 h, they completed the Psychomotor Vigilance Task (PVT)
      and rated on a seven-point scale how well they thought they could drive safely,
      react quickly in an emergency, and stay in their own lane. They were also asked
      to assess how they thought someone else in their own position could drive. The
      participants rated their driving ability as becoming significantly poorer at the
      same time that their PVT performance became significantly slower. Self-ratings
      indicating a qualitative assessment of poorer than neutral driving occurred at
      03:00 h for both the "drive safely" and "react quickly" questions, after 19 h of
      continuous wakefulness (starting at 08:00 h). This occurred at 05:00 h for the
      "keep in my lane" question. Previous studies with a similar protocol demonstrated
      that under these conditions, individuals exhibit a performance decrements
      equivalent to someone with a blood alcohol concentration of 0.05% (the legal
      driving limit in Australia). Participants consistently rated the ability of
      others to drive as poorer than their own. The main implication from this study
      for road safety and legal liability is that it is reasonable to focus on a
      person's perception of the situation, as it does align with objective reality to
      a certain extent. A concern in terms of road safety is potential overconfidence,
      indicated by rating others consistently poorer than themselves.

PMID- 17190711
TI  - Predicting the timing and duration of sleep in an operational setting using
      social factors.
AB  - In recent years, there has been increasing interest in the use of bio
      mathematical models to predict alertness, performance, and/or fatigue in
      operational settings. Current models use only biological factors to make their
      estimations, which can be limited in operational settings where social and geo
      physical factors also dictate when sleep occurs. The interaction between social
      and biological factors that help determine the timing and duration of sleep
      during layover periods have been investigated in order to create and initially
      validate a mathematical model that may better predict sleep in the field.
      Participants were 32 male transmeridian airline pilots (17 captains, 10 first
      officers, and 5 second officers) flying the Sydney-Bangkok-London-Singapore
      Sydney (SYD-LHR) pattern. Participants continued their regular schedule while
      wearing activity monitors and completing sleep and work diaries. The theoretical
      sleep timing model underpinning this analysis consists of separate formulations
      for short (<32 h) and long (>32 h) break periods. Longer break periods are split
      into three distinct phases-recovery (break start until first local night),
      personal (first local night until last local night), and preparation phases (last
      local night until break end)-in order to exploit potential differences specific
      to each. Furthermore, an iterative procedure combining prediction and
      retrodiction (i.e., using future duty timing information to predict current sleep
      timing) was developed to optimize predictive ability. Analysis found an
      interaction between the social and circadian sleep pressures that changed over
      the break period. Correlation analysis indicated a strong relationship between
      the actual sleep and new model's predictions (r = 0.7-0.9), a significant
      improvement when compared to existing models (r = 0.1-0.4). Social and circadian
      pressures play important roles in regulating sleep for international flight
      crews. An initial model has been developed in order to regulate sleep in these
      crews. The initial results have shown promise when applied to small sets of data;
      however, more rigorous validation must be carried out.

PMID- 17190712
TI  - Compensation for unfavorable characteristics of irregular individual shift rotas.
AB  - Some employees of TV companies, such as those who produce remote TV programs,
      have to cope with very irregular rotas and many short-term schedule deviations.
      Many of these employees complain about the negative effects of such on their
      wellbeing and private life. Therefore, a working group of employers, council
      representatives, and researchers developed a so-called bonus system. Based on the
      criteria of the BESIAK system, the following list of criteria for the ergonomic
      assessment of irregular shift systems was developed: proportion of night hours
      worked between 22 : 00 and 01 : 00 h and between 06 : 00 and 07 : 00 h,
      proportion of night hours worked between 01 : 00 and 06 : 00 h, number of
      successive night shifts, number of successive working days, number of shifts
      longer than 9 h, proportion of phase advances, off hours on weekends, work hours
      between 17 : 00 and 23 : 00 h from Monday to Friday, number of working days with
      leisure time at remote places, and sudden deviations from the planned shift rota.
      Each individual rota was evaluated in retrospect. If pre-defined thresholds of
      criteria were surpassed, bonus points were added to the worker's account. In
      general, more bonus points add up to more free time. Only in particular cases was
      monetary compensation possible for some criteria. The bonus point system, which
      was implemented in the year 2002 for about 850 employees of the TV company, has
      the advantages of more transparency concerning the unfavorable characteristics of
      working-time arrangements, incentive for superiors to design "good" rosters that
      avoid the bonus point thresholds (to reduce costs), positive short-term effects
      on the employee social life, and expected positive long-term effects on the
      employee health. In general, the most promising approach to cope with the
      problems of shift workers in irregular and flexible shift systems seems to be to
      increase their influence on the arrangement of working times. If this is not
      possible, bonus point systems may help to achieve greater transparency and
      fairness in the distribution of unfavorable working-time arrangements within a
      team, and even reduce the unnecessary unfavorable aspects of shift systems.

PMID- 17190713
TI  - Do short international layovers allow sufficient opportunity for pilots to
      recover?
AB  - For Australian pilots, short layovers (<40 h) are a feature of many international
      patterns. However, anecdotal reports suggest that flight crew members find
      patterns with short slips more fatiguing than those with a longer international
      layover, as they restrict the opportunity to obtain sufficient sleep. The current
      study aimed to determine whether pilots operating international patterns with
      short layovers have sufficient opportunity to recover prior to the inbound
      flight. Nineteen international pilots (ten captains, nine first officers)
      operating a direct return pattern from Australia to Los Angeles (LAX) with a
      short (n = 9) 9+/-0.8 h (mean+/-S.D) or long (n = 10) 62.2+/-0.9 h LAX layover
      wore an activity monitor and kept a sleep/duty diary during the pattern.
      Immediately before and after each flight, pilots completed a 5 min PalmPilot
      based psychomotor vigilance task (Palm-PVT). Flights were of comparable duration
      outbound (3.5+/-0.6 h) and inbound (14.3+/-0.6 h) and timing. The amount of sleep
      obtained in-flight did not significantly vary as a function of layover length.
      However, pilots obtained significantly more sleep during the inbound (3.7+/-0.8
      h) than the outbound flight (2.2+/-0.8 h). Pilots with the shorter layover
      obtained significantly less sleep in total during layover (14.0+/-2.7 h vs.
      19.6+/-2.5), due to significantly fewer sleep periods (3.0+/-0.7 vs. 4.0+/-0.9).
      However, neither mean sleep duration nor the sleep obtained in the 24 h prior to
      the inbound flight significantly differed as a function of layover length.
      Response speed significantly varied across the pattern, and a significant
      interaction was also observed. For pilots with a short layover, response speed
      was significantly slower at the end of both the outbound and inbound flight, and
      prior to the inbound flight (i.e., at the end of layover), relative to response
      speed at the start of the pattern (pre-trip). Similarly, response speed for the
      longer layover was slower at the end of the outbound flight compared to pre-trip
      (approaching significance, p = 0.073). However, response speed at the beginning
      of the inbound flight was significantly faster than pre-trip and did not
      significantly differ from pre-trip at the end of the inbound flight. The data
      suggest that short slips (<40 h) do not allow pilots the opportunity to obtain
      sufficient sleep to reverse the effects of fatigue accumulated during the
      outbound flight. As a result, their response speed prior to the inbound flight is
      substantially slower than the response speed of flight crew with a longer
      layover.

PMID- 17190714
TI  - Short sleep is associated with obesity among truck drivers.
AB  - Recent studies suggest that short-sleep duration is independently associated with
      obesity in the general population. The population of truck drivers is of
      particular interest, because they frequently work irregular shifts that in turn
      are associated with short-sleep duration. In addition, truck drivers have a high
      prevalence of sedentary habits, poor diet, and obesity. The present study aimed
      at verifying the association between sleep patterns and factors associated with
      obesity in this population. The study sample consisted in 4,878 truck drivers who
      participated in a campaign promoted by a highway company in the State of Sao
      Paulo, Brazil. This campaign offered highway truck drivers a medical and
      laboratorial evaluation. The truck drivers completed a questionnaire concerning
      demographic data, sleep duration, consumption of medications, and medical
      problems, such as diabetes, cardiopathy, and hypertension; as well as the Berlin
      questionnaire, which is able to discriminate low and high risk for obstructive
      sleep apnea. Blood samples were collected to measure glucose and cholesterol
      levels. Also, body weight and height were registered to calculate the body mass
      index (BMI). The mean age (+/-SD) of the truck drivers studied was 40+/-10 years.
      Out of the truck drivers analyzed, 28.3% (n = 1,379) had a BMI > or =30.0 Kg/m2
      (obesity). Among the 4,878 drivers included in the study, 1,199 (24.6%) were on
      medications and 334 (6.8%) were diabetic. Drivers (26.9%) with the greater BMI
      had a short sleep length. The independent factors associated with obesity were
      sleep duration <8 h/day (OR = 1.24), age >40 years (OR = 1.20), glucose levels
      >200 (OR = 2.02), cholesterol levels >240 (OR = 1.57), snoring (OR = 1.74), and
      hypertension (OR = 2.14). Smoking was not associated with obesity (OR = 0.69),
      and diabetes was considered a control variable. In conclusion, this study
      supports the hypothesis that short sleep duration as well as age >40 years are
      independently associated with obesity. This particular combination (short-sleep
      duration and obesity) is independently associated with several healthcare
      problems, including high levels of cholesterol, glucose, snoring, and
      hypertension. However, due to the cross-sectional nature of this study, no cause
      effect relationship can be drawn from these results.

PMID- 17190715
TI  - Extended working hours and health.
AB  - Statistical analyses of the relation between the amount of working hours and
      impairments to health, based on data from a European survey on working conditions
      in 2000, clearly reveal that there is a substantial correlation between the
      number of working hours per week and the frequencies of health complaints. This
      applies to both musculo-skeletal disorders as well as to psycho-vegetative
      complaints. The relationship of the duration of the exposure to working
      conditions to health impairments is moderated by a great number of individual
      (e.g., age) and situational (e.g., shift-work) variables, showing additive or
      interactive effects for which selected examples have been presented. In general,
      however, there is a consistent functional relationship between the number or
      working hours and their effects on the workers that holds over a great variety of
      conditions. It is argued that requests for extending working hours should thus be
      handled with care.

PMID- 17190716
TI  - Fatigue and mood correlates of sleep length in three age-social groups: School
      children, students, and employees.
AB  - The aim of the study was to trace the consequences of insufficient sleep, in
      terms of chronic sleep reduction rather than acute sleep deprivation, on fatigue,
      mood, cognitive performance self-estimations, and daytime sleepiness in different
      age-social groups. The age group of the subjects reflects their social situation
      and their working time organization: adolescents (n = 191) obeyed the strict
      school schedules with starting times often before 08:00 h; university students (n
      = 115) had more flexible timetables; young employees (n = 126) were engaged in
      regular morning schedules or irregular daytime hours or day and night shifts. A
      questionnaire study determined the declared need of sleep, self-reported sleep
      length, chronic fatigue (using a scale comprised of eight fatigue symptoms and
      four mood and three cognitive items), and daytime sleepiness (Epworth Sleepiness
      Scale). The declared need for sleep decreased in subsequent age groups from 9 h
      23 min in school children to 8 h 22 min in university students and to 7 h 37 min
      in young employees. Consequently, the discrepancy between preferred and real
      sleep length (sleep deficit) was the largest in adolescents: 106 min. Females
      showed a greater need of sleep than males (p = .025) and significantly more
      fatigue, mood, and cognitive problems; they also exhibited higher level of
      daytime sleepiness (p < .000). The sleep index (reported sleep length related to
      requirements) correlated significantly with all health issues in women (p <
      .000), while only with fatigue symptoms in men (p = .013). Actual sleep length
      was unrelated to mood and fatigue issues; the declared individual need of sleep
      and sleep index showed significant associations, especially in the group of
      adolescents. The most frequent complaints of adolescents included tiredness on
      awakening (46%), nervousness, and general weakness; university students reported
      excessive drowsiness (50%), tension, and nervousness; employees suffered mostly
      from negative moods, such as tension (49%), nervousness, and irritability. The
      findings of the study indicate that chronic sleep loss seems to affect females
      more severely than males. The associations of fatigue and mood with sleep need
      and sleep index were more pronounced in younger subjects. Surprisingly, fatigue
      symptoms in school children and university students were as frequent as in hard
      working adults. Because the problem of insufficient sleep is already present in
      youngsters, their work time organization needs more attention.

PMID- 17190717
TI  - Building-site camps and extended work hours: A two-week monitoring of self
      reported physical exertion, fatigue, and daytime sleepiness.
AB  - Large-scale construction work often requires people to work longer daily hours
      and more than the ordinary five days in a row. In order to minimize
      transportation times and optimize the use of personnel, workers are sometimes
      asked to live in temporary building-site camps in the proximity of the work site.
      However, little is known about the biological and psychological effects of this
      experience. The objective of the present study was to investigate whether
      exposure to long work hours and extended workweeks while living in building-site
      camps in between work shifts was associated with a build-up of increased
      complaints of poor sleep, daytime sleepiness, physical exertion, and fatigue
      across a two-week work cycle. Two groups of construction workers were examined.
      The camp group of 13 participants (mean age: 42+/-11 S.D. yrs) lived in building
      site camps and worked extended hours (between 07:00 and 18:00 h) and extended
      workweeks (six days in a row, one day off, five days in a row, nine days off).
      The home group of 16 participants (mean age 40+/-9 yrs) worked ordinary hours
      between 07:00 and 15:00 h and returned home after each workday. Self-ratings of
      daytime sleepiness (Karolinska Sleepiness Scale), physical exertion (Borg CR-10),
      and mood were obtained six or seven times daily during two workweeks. Fatigue
      ratings were obtained once daily in the evening, and ratings of sleep
      disturbances were obtained once daily in the morning with the Karolinska Sleep
      Diary. Data were evaluated in a repeated measures design. The results showed that
      both groups reported a similar level of daytime sleepiness, physical exertion,
      and mood across workdays and time points within a workday (all three-way
      interactions had p>0.898). Although the home group reported earlier wake-up
      times, the pattern of sleep disturbance ratings across the workdays did not
      differ between the groups. Both groups reported few sleep disturbances and good
      mood. However, the camp group reported higher physical exertion already at the
      start of work and showed a more gentle increase in ratings during the work shift
      and a smaller decline between the end of work and bedtime. The camp group also
      reported higher fatigue scores than the home group. However, none of the groups
      showed signs of increasing ratings in the progress of the two workweeks. For both
      groups, the ratings of daytime sleepiness formed a U-shaped pattern, with the
      highest scores at awakening and at bedtime. Yet, the camp group reported higher
      daytime sleepiness than the home group at lunch break and at the second break in
      the afternoon. In conclusion, there were no signs of fatigue build-up or
      accumulation of daytime sleepiness, physical exertion, or sleep disturbances in
      either group. Despite the fact that the camp group showed some signs of having
      trouble in recuperating in between work shifts, as indicated by the higher
      physical exertion ratings at the start of work, higher fatigue scores, and higher
      daytime sleepiness, the results constitute no real foundation for altering the
      camp group's current work schedule and living arrangements.

PMID- 17190718
TI  - The sleep, subjective fatigue, and sustained attention of commercial airline
      pilots during an international pattern.
AB  - International commercial airline pilots may experience heightened fatigue due to
      irregular sleep schedules, long duty days, night flying, and multiple time zone
      changes. Importantly, current commercial airline flight and duty time regulations
      are based on work/rest factors and not sleep/wake factors. Consequently, the
      primary aim of the current study was to investigate pilots' amount of sleep,
      subjective fatigue, and sustained attention before and after international
      flights. A secondary aim was to determine whether prior sleep and/or duty history
      predicted pilots' subjective fatigue and sustained attention during the
      international flights. Nineteen pilots (ten captains, nine first officers; mean
      age: 47.42+/-7.52 years) participated. Pilots wore wrist activity monitors and
      completed sleep and duty diaries during a return pattern from Australia to Europe
      via Asia. The pattern included four flights: Australia-Asia, Asia-Europe, Europe
      Asia, and Asia-Australia. Before and after each flight, pilots completed a 5 min
      PalmPilot-based psychomotor vigilance task (PVT) and self-rated their level of
      fatigue using the Samn-Perelli Fatigue Checklist. Separate repeated-measures
      ANOVAs were used to determine the impact of stage of flight and flight sector on
      the pilots' sleep in the prior 24 h, self-rated fatigue, and PVT mean response
      speed. Linear mixed model regression analyses were conducted to examine the
      impact of sleep in the prior 24 h, prior wake, duty length, and flight sector on
      pilots' self-rated fatigue and sustained attention before and after the
      international flights. A significant main effect of stage of flight was found for
      sleep in the prior 24 h, self-rated fatigue, and mean response speed (all p <
      0.05). In addition, a significant main effect of flight sector on self-rated
      fatigue was found (p < .01). The interaction between flight sector and stage of
      flight was significant for sleep in the prior 24 h and self-rated fatigue (both p
      < .05). Linear mixed model analyses indicated that sleep in the prior 24 h was a
      significant predictor of self-rated fatigue and mean response speed after the
      international flight sectors. Flight sector was also a significant predictor of
      self-rated fatigue. These findings highlight the importance of sleep and fatigue
      countermeasures during international patterns. Furthermore, in order to minimize
      the risk of fatigue, the sleep obtained by pilots should be taken into account in
      the development of flight and duty time regulations.

PMID- 17190719
TI  - Extending a model of shift-work tolerance.
AB  - The present study contributes to theory and practice through the development of a
      model of shift-work tolerance with the potential to indicate interventions that
      reduce nurses' intention toward turnover and increase job satisfaction in
      hospital-based settings. Survey data from 1257 nurses were used to conduct
      structural equation modeling that examine the direct and indirect effects of
      supervisor and colleague support, team identity, team climate, and control over
      working environment on time-based work/life conflict, psychological well-being,
      physical symptoms, job satisfaction, and turnover intention. The analysis of the
      proposed model revealed a good fit The chi-square difference test was non
      significant (chi2(26) = 338.56), the fit indices were high (CFI = .923, NFI =
      .918, and NNFI = .868), the distribution of residuals was symmetric and
      approached zero, the average standardized residual was low (AASR = .04), and the
      standardized RMR was .072. In terms of the predictor variable, the final model
      explained 48% of the variance in turnover intention. The data revealed
      considerable evidence of both direct effects on adjustment and complex indirect
      links between levels of adjustment and work-related social support, team
      identity, team climate, and control. Nurses with high supervisor and coworker
      support experienced more positive team climates, identified more strongly with
      their team, and increased their perceptions of control over their work
      environment. This in turn lowered their appraisals of their time-based work/life
      conflict, which consequently increased their psychological well-being and job
      satisfaction and reduced their physical health symptoms and turnover intention.
      The type of shift schedule worked by the nurses influenced levels of turnover
      intention, control over work environment, time-based work/life conflict, and
      physical symptoms.

PMID- 17190720
TI  - Can a shorter psychomotor vigilance task be used as a reasonable substitute for
      the ten-minute psychomotor vigilance task?
AB  - The 10 min psychomotor vigilance task (PVT) is commonly used in laboratory
      studies to assess the impact of sleep loss, sustained wakefulness, and/or time of
      day on neurobehavioral performance. In field settings, though, it may be
      impractical for participants to perform a test of this length. The aim of this
      study was to identify a performance measure that is sensitive to the effects of
      fatigue but less burdensome than a 10 min test. Sixteen participants (11 female,
      5 male; mean age = 21.7 years) slept in the sleep laboratory overnight then
      remained awake for 28 h from 08:00 h. During every second hour, participants
      completed three PVTs of differing duration (10 min, 5 min, 90 sec). For the 5
      min/10 min comparison, ANOVA indicated that response time was significantly
      affected by test length (F1,14 = 26.9, p < .001) and hours of wakefulness
      (F13,182 = 46.1, p < .001) but not by their interaction (F13,182 = 1.7, ns).
      There was a strong correlation between response time on the 5 and 10 min PVTs (r
      = .88, p < .001). For the 90 sec/10 min comparison, ANOVA indicated that response
      time was significantly affected by test length (F1,14 = 65.9, p < .001) and hours
      of wakefulness (F13,182 = 29.7, p < .001) as well as by their interaction
      (F13,182 = 6.0, p < .001). There was a strong correlation between response time
      on the 90 sec and 10 min PVTs (r = .77, p < .001). The effects of hours of
      wakefulness on neurobehavioral performance were similar for the 5 min and 10 min
      PVTs. In contrast, performance on the 90 sec PVT was less affected by hours of
      wakefulness than on the 10 min PVT. In addition, performance on the 10 min PVT
      was more highly correlated with the 5 min PVT than the 90 sec PVT. These data
      indicate that the 5 min PVT may provide a reasonable substitute for the 10 min
      PVT in circumstances where a test shorter than 10 min is required.

PMID- 17190721
TI  - Sleep on the job partially compensates for sleep loss in night-shift nurses.
AB  - Nursing personnel in Brazil are usually submitted to fixed 12 h shifts with no
      consecutive working days or nights. Moonlighting is common in this group, with a
      consequent increase in the number of working hours. The possibility of sleeping
      on the job during the night shift in the studied hospitals had already been
      described. The present study aims to analyze whether the time devoted to daily
      activities (sleep, rest, leisure, housework, commuting, personal needs, care of
      children or other people, non-paid work, and study) is related to the number of
      worked hours and to nap-taking during the night shift. The field study took place
      at two public hospitals in Rio de Janeiro, Brazil. Workers filled out a
      structured form on time devoted to the above-mentioned activities for at least
      four consecutive days. The time devoted to sleep was analyzed according to its
      occurrence at home or on the job. Workers were classified according to the number
      of jobs (one job/two jobs) and the time dedicated to work according to the median
      of the whole series (below the median/above the median). All workers who had at
      least one working night were analyzed as to nap-taking on the job. They were
      classified according to the sleep occurrence during the night shift-the sleep
      group and the non-sleep group, both of which were compared to daytime workers.
      Statistical treatment of data included non-parametrical procedures. The study
      group comprised 144 workers (mean age: 35.7+/-10.5 years old; 91% women; 78%
      nurse assistants, the remainder registered nurses). They recorded their daily
      activities for 4-11 days; 829 cumulative days were analyzed for the whole group.
      A total of 165 working nights were analyzed; sleep or rest occurred during 112
      (68%) of them, with mean sleep/rest duration of 141+/-86 min. Time devoted to
      sleep and leisure varied according to the number of working hours, being
      significantly reduced in those submitted to longer work hours (p < 0.001 and p =
      0.002, respectively). Results close to significance point to a reduction in the
      time dedicated to housework among workers with long work hours (p = 0.053). The
      time spent on sleep/rest per working night did not differ according to the number
      of worked hours (p = 0.490). A tendency was observed for those who have two jobs
      to devote more time to sleep/rest on the job (p = 0.058). The time of personal
      needs was significantly lower among those who did not sleep on the job as
      compared to day workers (p = 0.036). The total sleep time was significantly lower
      among those who did not sleep on the job, as compared to day workers and to those
      who slept on the job (p = 0.004 and p = 0.05, respectively). As to home sleep
      length, workers who slept and those who did not sleep on the job were similar and
      slept significantly less than exclusively daytime workers (p < 0.001 and p =
      0.002, respectively). Sleeping on the job during the night shift seems to
      partially compensate for the shorter sleep at home among night workers and may
      play a beneficial effect in coping with two jobs.

PMID- 17190722
TI  - Development and preliminary validation of an index for indicating the risks of
      the design of working hours to health and wellbeing.
AB  - BASS 4, a computer program for the design and evaluation of workings hours, is an
      example of an ergonomics-based software tool that can be used by safety
      practitioners at the shop floor with regard to legal, ergonomic, and economic
      criteria. Based on experiences with this computer program, a less sophisticated
      Working-Hours-Risk Index for assessing the quality of work schedules (including
      flexible work hours) to indicate risks to health and wellbeing has been developed
      to provide a quick and easy applicable tool for legally required risk
      assessments. The results of a validation study show that this risk index seems to
      be a promising indicator for predicting risks of health complaints and wellbeing.
      The purpose of the Risk Index is to simplify the evaluation process at the shop
      floor and provide some more general information about the quality of a work
      schedule that can be used for triggering preventive interventions. Such a risk
      index complies with practitioners' expectations and requests for easy, useful,
      and valid instruments.

PMID- 17190723
TI  - Psychosocial work characteristics predicting daytime sleepiness in day and shift
      workers.
AB  - Characteristics of work organization other than working time arrangements may
      contribute importantly to daytime sleepiness. The present study was designed to
      identify the psychosocial factors at work that predict daytime sleepiness in a
      sample of day and shift workers. Participants working at a pulp and chemical
      factory completed an annual questionnaire regarding psychosocial factors at work
      using the U.S. National Institute for Occupational Safety and Health Generic Job
      Stress Questionnaire (i.e., quantitative workload, variance in workload, job
      control, support from supervisor, coworkers, or family/friends, job satisfaction,
      and depressive symptoms), as well as daytime sleepiness (through the Epworth
      Sleepiness Scale [ESS]) and sleep disturbances for three years starting in 2002
      (response rates, 94.6-99.0%). The present analysis included 55 day workers (11
      women) and 57 shift workers (all men) who participated in all three years of the
      study, worked under the same work schedule throughout the study period, and had
      no missing data on any of the daytime sleep items. A repeated-measures analysis
      of covariance (ANCOVA) was used to test the effects of work schedule (day vs.
      shift work) and psychosocial factors at work in 2002 on the ESS scores in
      subsequent years, with sleep duration, insomnia symptoms, chronic diseases, and
      sleepiness levels at baseline as covariates. Given significant and near
      significant interactions of work schedules with psychosocial factor or study
      year, the ANCOVA, with the factors of psychosocial work characteristics and study
      year, was performed by type of work schedule. The results indicated a significant
      main effect of psychosocial work characteristics (p = 0.010, partial eng2 = 0.14)
      and an almost significant main effect of study year (p = 0.067, partial eng2 =
      0.06) and interaction between psychosocial work characteristics and study year (p
      = 0.085, partial eng2 = 0.06) for variance in workload among the day work group.
      The day workers reporting high variance in workload in 2002 exhibited
      significantly higher ESS scores in 2003 and 2004 than did those reporting low
      variance in workload. The ANCOVA for the shift work group showed a main effect of
      psychosocial work characteristics for job satisfaction (p = 0.026, partial eng2 =
      0.10) and depressive symptoms (p = 0.094, partial eng2 = 0.06) with the
      interaction between psychosocial work characteristics and study year for job
      satisfaction (p = 0.172, partial eng2 = 0.04) and depressive symptoms (p = 0.035,
      partial eng2 = 0.07). The shift workers with low job satisfaction and high
      symptoms of depression in 2002 showed significantly greater ESS scores in 2003
      and/or 2004 than did those with opposite characteristics. These results may
      suggest a potential predictive value of variance in workload for day workers as
      well as job satisfaction and depressive symptoms for shift workers with respect
      to daytime sleepiness. The present findings may imply that redesigning these
      aspects of work environment would be of help in managing daytime sleepiness.

PMID- 17190724
TI  - The impact of rest breaks on temporal trends in injury risk.
AB  - This study examined the impact of rest breaks on temporal trends in industrial
      accident risks in an attempt to replicate earlier findings of a linear increase
      in risk as a function of elapsed time on task. In two separate studies, the trend
      in work-related injuries were studied in relation to the timing of rest breaks.
      In study one, comparisons were made between on- and off-track workers on weekly
      rotating three-shift systems operating in a large engineering company. Records of
      on-duty injuries that occurred over 12 months were examined (N = 4645 incidents).
      Study two involved interviewing patients who had suffered work-related hand
      injuries in a variety of occupational settings (N = 407 patients). Hierarchical
      log linear analysis was used in both studies. In study one, risk increased from
      the first to the second half-hour of continuous work following a break, but then
      remained relatively constant in subsequent half-hour periods, although there was
      a fall in the third half-hour for on-track workers. In some of the data, there
      was also a decrease in risk in the period leading up to the end of a work period.
      There was a sharp decline in reported injuries toward the very end of a shift,
      but otherwise the observed trends did not differ between successive periods of
      continuous work or between morning, afternoon, and night shifts. In study two,
      risk increased from the first to the second half-hour of continuous work and then
      remained relatively constant in the third half-hour. The contrast between the
      current and previous findings may be due to the relatively unique work
      environment of the previous study. It is suggested that the current trends
      reflect the effects of working in a relatively unconstrained task environment,
      and that causes other than fatigue may underlie the trends observed in both the
      previous and current studies.

PMID- 17190726
TI  - Circadian variation of the myocardial ischemic threshold in patients with
      ischemic heart disease.
AB  - PURPOSE: Circadian variation of the heart rate (HR) at the myocardial ischemic
      threshold was compared with that of the HR at the sympathetic tone threshold in
      16 cases of effort angina pectoris. METHODS: The high (0.15-0.40 Hz, Hf) and low
      (0.03-0.15 Hz, Lf) frequency spectral components were extracted every twenty
      seconds, using frequency domain analysis of the RR interval recorded by a 24-hour
      Holter ECG with an accelerometer. HR-Hf data collected every five minutes were
      plotted as the X-Y coordinates, and a two-compartment analysis was performed. The
      HR at the autonomic tone threshold was then determined at the intersection point
      of the lines. A loop of the HR-ST segment was drawn during walking to determine
      the ischemic threshold at which heart rate ischemic ST segment depression began
      and circadian variation was observed. RESULTS: The circadian rhythm at the
      sympathetic tone threshold and the HR at the ischemic threshold were high during
      the day and low at night. The HR at the ischemic threshold was 15-20% higher than
      that at the sympathetic tone threshold at night but only 9-13% higher during the
      day. Also, there was a period during which there was no significant difference
      between the HR at the two thresholds. CONCLUSION: In comparing circadian
      variation between HR at the sympathetic tone threshold and HR at the ischemic
      threshold, there was a period during which there was no significant difference
      between the HRs. This might suggest a period in which a high incidence of cardiac
      ischemic attack is likely. This information could provide a feasible indicator
      for appropriate exercise training for patients with ischemic heart disease.

PMID- 17190727
TI  - Long-acting calcium channel blocker, azelnidipine, increases endothelial nitric
      oxide synthase in the brain and inhibits sympathetic nerve activity.
AB  - Nitric oxide (NO) in the central nervous system inhibits sympathetic nerve
      activity, thereby decreasing blood pressure. It is unknown, however, whether
      orally administered antihypertensive treatment alters NO synthase (NOS)
      expression, particularly in the brain, and how changes in NOS expression affects
      sympathetic nerve activity. Azelnidipine, a recently developed long-acting
      dihydropyridine calcium channel blocker, does not cause baroreflex-induced
      tachycardia. The aim of the present study was to determine whether
      antihypertensive treatment with azelnidipine alters endothelial NOS (eNOS),
      neuronal NOS (nNOS), or inducible NOS (iNOS) expression in the brain, and how
      changes in NOS affect sympathetic nerve activity. Azelnidipine (20 mg/kg/day) or
      hydralazine (20 mg/kg/day) was orally administered for 30 days in stroke-prone
      spontaneously hypertensive rats (SHRSP). Blood pressure and heart rate were
      measured by the tail cuff method. Urinary norepinephrine excretion was measured
      as a marker of sympathetic nerve activity. Western blot analysis was performed to
      examine eNOS, nNOS, or iNOS expression levels in the brain (cortex, cerebellum,
      hypothalamus, and the brain stem), heart, and aorta. The extent of blood pressure
      reduction was similar between the two groups. Heart rate increased in the
      hydralazine-treated group but did not change in the azelnidipine-treated group.
      Urinary norepinephrine excretion was significantly increased only in the
      hydralazine-treated group. Treatment with azelnidipine significantly increased
      eNOS expression levels in the brain, heart, and aorta, but did not alter nNOS or
      iNOS expression levels. Treatment with hydralazine did not change any of the NOS
      expression levels. These results suggest that antihypertensive treatment with
      azelnidipine attenuates reflex-induced sympathetic activation and enhances eNOS
      expression levels in the brain as well as in the heart and aorta.

PMID- 17190728
TI  - Exclusion of influence of physical activity on ambulatory blood pressure.
AB  - OBJECTIVE: The basal blood pressure (BP) is more intimately related to
      hypertension severity than casual BP. BP values obtained by ambulatory blood
      pressure monitoring (ABPM) tend to be influenced by patients' physical activity
      because values are not always obtained with the patient at rest. The purpose of
      this study was to estimate the influence of physical activity on BP and determine
      daytime BP adjusted for activity as measured by ABPM. METHODS: This study
      targeted three clinically different groups: healthy medical students (HS, n =
      40), patients with hypertension (HT, n = 20), and patients with diabetes mellitus
      (DM, n = 7). The subjects' BP, heart rate (HR), and physical activity level were
      measured by a noninvasive portable multi-biomedical recorder. To identify the
      influence of physical activity on BP in the three study groups, a least squares
      regression analysis of the relation between BP and ACT (an index of activity with
      acceleration) was performed for each group. RESULTS: ACT had a positive influence
      on systolic BP (SBP) in the HS, HT, and DM groups (R2 = 0.319, 0.576, 0.697,
      respectively). SBP adjusted for ACT (walking level) by means of the regression
      model with dummy variable was 0-24 mmHg lower than the value of SBP measured by
      ABPM, and daytime SBP (walking level) was overestimated by approximately 10 mmHg
      in comparison to the value of SBP at rest (ACT = 0). CONCLUSION: Physical
      activity had a positive effect on SBP. The results showed that physical activity
      (walking-level) had a positive effect on SBP of about 10 mmHg.

PMID- 17190729
TI  - A possible relationship of nocturnal blood pressure variability with coronary
      artery disease in diabetic nephropathy.
AB  - Evidence suggests a relationship between short-term blood pressure (BP)
      variability and cardiovascular target-organ damage. Although a blunted nocturnal
      decrease in BP and reduced heart rate variability have been shown to be
      associated with cardiovascular morbidity in diabetic patients, little information
      is available on short-term BP variability. In this study, short-term BP
      variability was assessed in 36 subjects with type 2 diabetes and overt
      nephropathy who underwent ambulatory BP monitoring, and the factors that
      correlated with short-term BP variability were examined. The incidence of
      coronary artery disease (CAD) was significantly greater in the patients with
      increased 24-h systolic BP variability (67% versus 11%; p < 0.0005), while that
      of cerebrovascular disease was not significantly affected (61% versus 50%).
      Multiple stepwise regression analysis revealed that serum cholesterol
      (cholesterol) and plasma norepinephrine (p-NE) were significant and independent
      contributors to nighttime systolic BP variability (partial R2 = 0.490, p < 0.001;
      partial R2 = 0.470, p < 0.001) and demonstrated that body mass index and p-NE
      were primary determinants of nighttime diastolic BP variability (partial R2 =
      0.539, p < 0.0005; partial R2 = 0.304, p < 0.05). Diabetic nephropathy patients
      with CAD had significantly increased daytime systolic (17.8 mmHg versus 13.1
      mmHg, p < 0.0005), nighttime systolic (17.4 mmHg versus 10.5 mmHg, p < 0.0001),
      and nighttime diastolic (10.4 mmHg versus 7.2 mmHg, p < 0.05) BP variability.
      Furthermore, logistic regression analysis demonstrated that nighttime systolic BP
      variability was an independent risk factor for CAD (odds ratio 3.13 [95% CI 1.02
      9.61]; p < 0.05). The increase in nighttime BP variability is associated with a
      proportional sympathetic activation in diabetic nephropathy. Elevated short-term
      BP variability combined with relative sympathetic prevalence during the night
      might represent an important risk factor for cardiovascular events in the
      diabetic population.

PMID- 17190730
TI  - Effects of nighttime alcohol intake on evening and next morning home blood
      pressure in Japanese normotensives.
AB  - Home blood pressure (HBP) is usually measured in the morning and evening, but the
      evening HBP tends to be influenced by an individual's behavior pattern, such as
      bathing and drinking, which are often seen in the Japanese. In this study, in
      order to elucidate the influence of nighttime drinking on the evening and next
      morning HBP and heart rate (HR), HBP measurement was performed in Japanese
      normotensives under conditions in which the influence of bathing was minimized.
      Among 700 registered volunteers, 245 normotensives (189 male, 56 female, mean
      age; 35.8 +/- 0.5 years old) whose data consisted of a combination of drinking
      and non-drinking on workdays were selected. A semi-automatic device was lent to
      all participants, and they were asked to perform triplicate morning and evening
      measurements on seven consecutive days between October 16, 2002, and November 13,
      2002. The differences in evening HBP and HR between the drinking and non-drinking
      days were calculated, as were the differences in the next morning HBP and HR.
      Only data of evening HBP measured at least 30 min after bathing were accepted.
      Evening SBP and DBP on drinking days were significantly lower (2.5 +/- 0.5 mmHg,
      3.1 +/- 0.5 mmHg) than those on non-drinking days. On the other hand, evening HR
      on drinking days was significantly higher (7.7 +/- 0.8 b.p.m.) than that on non
      drinking days. Although there was no difference in morning SBP after days with
      and without drinking, morning DBP the day after drinking was slightly (0.8 +/-
      0.3 mmHg) but significantly lower than that the day after non-drinking. Morning
      HR the day after drinking was significantly higher (2.4 +/- 0.4 b.p.m.) than that
      after non-drinking. Because nighttime drinking influenced the evening HBP even in
      normotensives, it was suggested that morning HBP could give more stable values
      than evening HBP in Japanese people.

PMID- 17190731
TI  - Relation between nocturnal arterial oxygen desaturation and morning blood
      pressure.
AB  - OBJECTIVE: Arterial oxygen saturation (SpO2) in volunteers had been previously
      investigated, and the possibility that a decrease in SpO2 leads to an increase in
      blood pressure (BP) in airline passengers experiencing oxygen desaturation at
      high altitudes was reported. It was also shown that mean nocturnal SpO2 was lower
      in subjects with high-normal BP or mild hypertension than in those with normal
      BP. The present study investigated nocturnal SpO2, evening BP, and morning BP of
      volunteers during daily life and examined the relation between nocturnal SpO2 and
      change in BP (morning BP minus evening BP) to determine the influence of SpO2 on
      BP. METHODS: Sixty-two volunteers (31 men and 31 women) aged 40-87 years (mean:
      55.9 +/- 12 [SD] years) underwent measurement of SpO2 and heart rate with a ring
      shaped pulse oximeter during sleep at home. Evening BP and morning BP were
      measured by automatic BP recorder. Subjects that were classified as having high
      SpO2 (mean nocturnal SpO2 >or= 95%; n = 23, 10 men and 13 women; mean age: 53.2
      +/- 12 years) or low SpO2 (mean nocturnal SpO2 < 94%; n = 21, 12 men and 9 women;
      mean age: 58.7 +/- 13 years) were compared. The relation between mean nocturnal
      SpO2 and morning BP and the relation between mean nocturnal SpO2 and change in BP
      were investigated. RESULTS: There was a significant negative correlation between
      mean nocturnal SpO2 and morning systolic BP (SBP; r = -0.50, p < 0.01) and
      between mean nocturnal SpO2 and morning diastolic BP (DBP; r = -0.37, p < 0.01).
      A significant negative correlation between mean nocturnal SpO2 and change in SBP
      was observed (r = -0.57, p < 0.01). Morning BP was significantly higher in the
      low nocturnal SpO2 group than in the high nocturnal SpO2 group (p < 0.001).
      CONCLUSION: The increase in morning BP from evening BP was significantly greater
      in subjects with a low nocturnal SpO2. The decrease in SpO2 during sleep may
      affect morning BP rise.

PMID- 17190732
TI  - Investigation of major genetic polymorphisms in the Renin-Angiotensin-aldosterone
      system in subjects with young-onset hypertension selected by a targeted-screening
      system at university.
AB  - Although polymorphisms in renin-angiotensin-aldosterone (RAA) system genes for
      angiotensinogen (AGT M235T), angiotensin-converting enzyme (ACE I/D), angiotensin
      II type 1 receptor (AT1 A/C1166), and aldosterone synthase (CYP11B2-344T/C) have
      been major targets for genetic investigation in association with essential
      hypertension (EH), the influence of these genetic factors is still to be
      determined. Because patients with young-onset EH are thought to possess a
      stronger genetic background than EH patients who show elevated BP relatively late
      in life, the targeted screening of hypertensive students in Tohoku University was
      completed for the selection of subjects for genetic investigation. Out of 16,434
      students (12,794 males and 3,670 females) younger than 30, 22 students showed a
      high blood pressure (BP) (systolic and diastolic BP of 140 and/or 90 mmHg or
      greater, respectively, on two occasions and more than 135 and/or 85 mmHg,
      respectively, at a third measurement during casual BP measurements at the Tohoku
      University Health Center. These 22 students were asked to measure their BP at
      home (HBP). Six of the students had a systolic HBP of more than 135 mmHg and/or a
      diastolic HBP of more than 85 mmHg, and these students subsequently received
      medical examinations at Tohoku University Hospital and were diagnosed with EH.
      Genotyping for the four major genetic polymorphisms mentioned above was performed
      on the six students with EH and on 12 of the remaining 16 students whose HBP was
      within the normal range (white coat hypertension: WCH). Neither the EH nor the
      WCH students showed a different distribution of genotypes and allelic
      frequencies, compared to those found in the general Japanese population. Hence,
      the present study suggests that none of the major genetic polymorphisms in the
      RAA system strongly influence the onset of EH.

PMID- 17190733
TI  - Progress report on The Hypertension Objective Treatment Based on Measurement by
      Electrical Devices of Blood Pressure (HOMED-BP) study: status at February 2004.
AB  - The Hypertension Objective Treatment Based on Measurement by Electrical Devices
      of Blood Pressure (HOMED-BP) Study is the first large-scale intervention trial in
      Japan using a PROBE design to determine an optimal target blood pressure (BP)
      level on the basis of self-measured BP at home and optimal initial
      antihypertensive medication. The registered patients are randomized to one of two
      different BP levels and to initial antihypertensive regimens (i.e., calcium
      antagonist [Ca-A], angiotensin-converting enzyme inhibitor [ACE-I], or
      angiotensin II receptor antagonist [ARB]). At the end of February 2004, 2729,
      1687, and 971 patients were recruited, randomized, and followed-up for 12 months
      or more. Among the 971 patients, mean systolic/diastolic BP levels at
      randomization in the Ca-A, ACE-I, and ARB groups were 150/90, 152/89, and 151/89
      mmHg, respectively. These values reduced after six months of Ca-A-, ACE-I-, and
      ARB-based treatment (133/81 mmHg, 135/80 mmHg, and 134/79 mmHg, respectively) and
      further reduced after 12 months (131/80 mmHg, 134/79 mmHg, and 132/79 mmHg,
      respectively) without any significant differences among groups. In more intensive
      and less intensive BP-lowering groups, mean systolic/diastolic BP levels at
      randomization were 151/90 and 150/89 mmHg, respectively. Although BP levels
      reduced after 6-month (135/80 mmHg and 133/80 mmHg, respectively) and 12-month
      treatment (133/79 mmHg and 132/80 mmHg, respectively) in each target group, no
      significant difference in BP values was observed between groups. These results
      indicate the necessity of additional interventional strategies to improve the
      achievement of target BP levels, especially in the more intensive BP-lowering
      group.

PMID- 17190734
TI  - The effect of SHJKS on cytokines production and NF-kappaB activation in the
      peripheral blood mononuclear cells of patients with cerebral infarction.
AB  - The Korean genuine medicine "Seonghyangjeongkisan" (SHJKS) has long been used for
      various cerebrovascular diseases. However, very little scientific investigation
      has been carried out. Cytokines involved in the regulation of inflammatory
      reactions and immune responses may play a role in the pathogenesis of cerebral
      infarction (CI). The aim of the present study is to elucidate how SHJKS modulates
      the inflammatory reaction in lipopolysaccaride (LPS) plus phytohaemagglutinin
      (PHA)-stimulated peripheral mononuclear cells (PBMCs) from CI patients. The
      amount of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL
      8 in PBMC culture supernatant was significantly increased in the LPS plus PHA
      treated cells compared to unstimulated cells. SHJKS inhibited the TNF-alpha, IL
      1beta, IL-6, and IL-8 production in dose dependent manner. Maximal inhibition
      rate of the TNF-alpha, IL-1beta, IL-6, and IL-8 by SHJGS (1.0 mg/ml) was 68.01 +/
      0.28% (P < 0.01), 52.11 +/- 0.56 % (P < 0.01), 53.42 +/- 0.46 % (P < 0.01), and
      46.70 +/- 0.37% (P < 0.05), respectively. In addition, we show that SHJKS
      suppressed nuclear factor (NF)-kappaB activation induced by LPS plus PHA, leading
      to suppression of IkappaB-alpha phosphorylation and degradation. These results
      suggest that SHJKS might have regulatory effects on LPS plus PHA-induced cytokine
      production and NF-kappaB activation, which might explain its beneficial effect in
      the treatment of CI.

PMID- 17190735
TI  - Cytolytic and cytotoxic activity of a human natural killer cell line genetically
      modified to specifically recognize HER-2/neu overexpressing tumor cells.
AB  - NK92 cells genetically engineered to recognize the HER-2/neu oncoprotein have
      been previously reported to lyse HER-2/neu positive tumor cell lines through
      direct cell to cell contact. In the present study we have transduced NK92 cells
      with a chimeric receptor gene composed of the HER-/neu specific scFv (FRP5)
      antibody fragment, joined to the peptide CD8 hinge region and the signaling CD3
      zeta chain. NK92 cells expressing this chimeric receptor (NK92.HER-2/neu/zeta)
      specifically recognized and lysed HER-2/neu overexpressing tumor cell lines both
      in vitro and in preclinical tumor models in vivo. More important we demonstrate
      that NK92.HER-2/neu/zeta cells constitutively secrete high levels of soluble scFv
      which mediate strong tumor cytostatic effects by directly binding on cell surface
      HER-2/neu. Our data uncover an additional mechanism through which NK92.HER
      2/neu/zeta cells mediate antitumor effects and further support their use in cell
      based therapeutics for the treatment of HER-2/neu expressing cancers.

PMID- 17190736
TI  - Calcitriol prolongs recipient survival by inducing expression of zinc-finger
      protein A20 and inhibiting its downstream gene following rat orthotopic liver
      transplantation.
AB  - Calcitriol has important immunomodulation action and can prolong recipient
      survival after organ transplantation. The data in this study demonstrated that
      treatment of liver allograft recipient with calcitriol can protect allograft from
      acute rejection and prolong recipient's survival. Calcitriol inhibited expression
      of proinflammatory cytokine such as Interleukin-2 and Interferon-gamma
      intragraft. It also inhibited expression of nuclear factor kappaB (NF-kappaB)
      significantly as a result of enhancing its inhibitory protein I kappa B
      (IkappaB). As well, expression of zinc-finger protein A20 (A20) was enhanced
      significantly. The results suggest that calcitriol exerts its immunosuppression
      action in part through inducement of the A20, IkB, inhibition of NF-kB, and
      resultant proinflammatory expression pathway.

PMID- 17190737
TI  - A pilot study of an anti-MRSA bio-engineered lacteal complex (anti-MRSA BLC) in a
      murine septicemia model.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen of
      humans and other animals, causing septicemia, abcessation, toxemia, and other
      infectious diseases. Refined bioengineered lacteal complex (BLC), made
      specifically against MRSA, is a novel complex of low molecular weight immunogenic
      and antimicrobial molecules. It was evaluated in vivo using a mouse model of MRSA
      induced peritonitis. Intraperitoneal dosing of anti-MRSA BLC demonstrated a
      therapeutic effect (83% survival) against an intraperitoneal MRSA challenge that
      caused 100% mortality in untreated animals. Anti-MRSA BLC is a promising
      therapeutic modality for MRSA infection.

PMID- 17190738
TI  - FK506: an immunosuppressive agent preserving HIF-1 activity.
AB  - During transplantation, donor organs or cells are subjected to hypoxia. Hypoxia
      inducible factor-1 (HIF-1) is essential for cellular adaptation to hypoxia.
      Immunosuppressive agents should be used for preventing graft rejection, but of
      these, rapamycin and cyclosporine A have been reported to inhibit HIF-1. We
      examined whether or not another important immunosuppressant, FK506, inhibits HIF
      1. In contrast to cyclosporine A, FK506 neither inhibits HIF-1alpha expression in
      8 different cell lines, nor represses the transcriptional activity of HIF-1.
      Compared with cyclosporine A, FK506 significantly reduced the apoptotic cell
      death by hypoxia. FK506 could preserve HIF-1 activity in donor organs subjected
      to hypoxia.

PMID- 17190739
TI  - Upregulation of the axonal growth and the expression of substance P and its NK1
      receptor in human allergic contact dermatitis.
AB  - Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related
      peptide (CGRP) have been reported to be involved in allergic contact dermatitis
      (ACD). In the present study, we investigated the general innervation (using
      antibody against protein gene product 9.5, PGP 9.5), axonal growth (using
      antibody against growth associated protein, GAP-43), CGRP, and substance P with
      its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel
      sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after
      challenge with the antigen. There was an increased (p < 0.01) number of GAP-43
      positive fibers in the eczematous compared with control skin, indicating an
      increased axonal growth already at 72 hr postchallenge. Double staining revealed
      a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference
      in the number of substance P and CGRP positive nerve fibers between eczematous
      and control skin. However, semiquantification analyses showed an increased
      expression of substance P positive inflammatory cells, being CD3, CD4, or CD8
      positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive.
      These results indicate a contribution of regenerating nerve fibers and substance
      P to the contact allergic reaction.

PMID- 17190740
TI  - Bridges between nervous and immune systems: their disconnection and clinical
      consequences.
AB  - Nervous and immune systems are connected by several mutual links, thus
      constituting a diffuse functional network in the body. In particular,
      neurohormones, neuropeptides, and cytokines represent the major mediators of the
      so-called psychoneuroendocrinoimmune axis. In this review, special emphasis is
      placed on certain pathologies characterized by a disconnection of the existing
      bridges between nervous and immune systems. For instance, spinal cord injury
      (SCI) is a clinical condition in which loss of neurons and very poor axon growth
      represent the main features. The role played by infiltrating and resident
      immunocompetent cells is still debated in SCI. However, to enhance axon growth in
      SCI, current therapeutic attempts are based on the stimulation of the immune
      response within the central nervous system, thus triggering either cell-mediated
      or humoral immune responsiveness.

PMID- 17190741
TI  - The 18S rRNA is basically composed of two tandem quasirepeats. Insights into the
      evolution of some innate immunity receptors.
AB  - The gene encoding the 18S rRNA is an ancient molecule and its basic structure has
      been highly conserved from fish to mammals. Recently, we compared the nucleotide
      sequences of the human 18S rRNA and the human formyl peptide receptor 1 mRNA and
      concluded that selected segments of the two sequences exhibit similarities that
      are unlikely to be due simply to chance. Other data suggest the existence of
      nonrandom similarities between the 18S rRNA and the chemokine CXC receptor 4
      mRNA. Therefore we advance the hypothesis that some groups of genes encoding 7
      transmembrane G-coupled receptors of immunological interest may be evolutionarily
      related to the 18S gene. In this article we analyze the base-sequence
      architecture of the human 18S rRNA in terms of similarities between selected
      segments within the molecule. The method of study was based on the recording of
      the positions of 7- to 11-base oligonucleotide repeats, followed by a
      probabilistic analysis of the random occurrence of the repeats. Herein we show
      that most of the 18S rRNA molecule appears to be composed of two long tandem
      quasirepeats. We hypothesize that an ancestral gene structure composed of a chain
      of about 850 nucleotides duplicated to form a two-unit tandem repeat. Then the
      two units diverged as a consequence of independent nucleotide mutations,
      deletions, and insertions, but still retaining recognizable homologies. In
      addition, further nonduplicated shorter segments were added to build up the
      complete sequence.

PMID- 17190742
TI  - New insights into the biological and clinical significance of fecal calprotectin
      in inflammatory bowel disease.
AB  - Nowadays, calprotectin, a cytoplasmatic protein, released by activated
      neutrophilic polymorphonuclear cells (PMN) and/or monocytes-macrophages (MO), is
      considered a good indicator of inflammation in several diseases. Accordingly,
      fecal calprotectin represents a good predictor of clinical relapse in ulcerative
      colitis (UC) patients, whereas conflicting results have been reported in Crohn's
      disease (CD) patients. In our study, in 76 IBD patients (29 CD and 47 UC) fecal
      calprotectin has been evaluated by a commercial ELISA kit. Results demonstrate
      that levels of this protein in the stool are significantly more elevated in
      active CD and UC patients than in normal volunteers. In quiescent CD and UC a
      trend to higher levels of calprotectin than in the normal counterpart is,
      however, evident. These data suggest that a low-grade inflammation of the
      intestinal wall is always present in CD and UC patients, which may predict a
      clinical relapse risk. In the same group of patients calprotectin levels also
      were analyzed according to sex and age. A trend to higher values of calprotectin
      was present in male patients with active or quiescent CD than in their female
      counterparts. Only in UC patients in remission a trend to calprotectin increase
      was more marked in the male group than in the female counterpart. When CD and UC
      patients were divided up according to age, calprotectin positivity peaked between
      30-39 years in active CD patients, while in quiescent CD maximum positivity was
      between 40 and 49 years. However, in both active and quiescent UC patients,
      calprotectin positivity increased with age. The more precocious detectability of
      fecal calprotectin in CD patients, as a marker of intestinal mucosa inflammation,
      may be related to the different histopathology of the two diseases (CD versus
      UC). However, reduced PMN and/or MO trafficking from peripheral blood to
      intestinal mucosa with age by effects of chronic treatment should not be ignored
      in CD patients.

PMID- 17190743
TI  - Inhibition of mite-induced immunoglobulin E synthesis, airway inflammation, and
      hyperreactivity by herbal medicine STA-1.
AB  - The availability of STA-1 in suppressing allergen-induced immunoglobulin E (IgE)
      synthesis, airway inflammation and hyperreactivity in a murine model was
      investigated. The mice were intraperitoneally sensitized with Dermatophagoides
      pteronyssinus group 5 allergen (Der p 5) and orally treated with 300 mg/kg of STA
      1 every other day for 14 days. The Der p 5-specific immunologic responses
      including changes of specific immunoglobulin G and E, cells in the broncholarvage
      fluid, and airway hyperreactivity were measured when mice received inhalation
      challenge with Der p 5 after sensitization for 21 days. By comparing with sham
      treated groups, the synthesis of Der p 5-specific IgE was downregulated while the
      influx of eosinophils and neutrophils in the airway were remarkably reduced. In
      addition, Der p 5-induced airway hyperreactivity also was significantly
      eliminated by STA-1 treatment. These results showed that STA-1 could effectively
      suppress the Der p 5-induced allergic reactions, and the availability of STA-1
      for the treatment of allergic asthma was demonstrated in this study.

PMID- 17190744
TI  - Sensitization of naive beagles by intradermal injection of an ascaris antigen:
      induction of a model of skin allergy.
AB  - Ascaris suum-hypersensitive beagles represent a unique model of skin allergy.
      Despite its suitability, the need to test numerous dogs prior to the selection of
      natural positive responders causes many complications. We hypothesized that the
      model could be induced in adult beagles by primary sensitization. Ten dogs were
      included in an intradermal sensitization program using ascaris antigen and were
      thereafter tested for cutaneous reaction. After 2 weeks, 60% developed a positive
      reaction that lasted for months. We therefore present a straightforward method to
      establish the Ascaris canine model of allergy that will extend its availability
      for research in cutaneous allergy immunomodulation.

PMID- 17190745
TI  - Distinct requirements for interleukin-6 in airway inflammation induced by diesel
      exhaust in mice.
AB  - To clarify the possible role of interleukin-6 in aggravation of inflammatory
      responses in diesel exhaust-exposed mice, we compared the infiltration of
      inflammatory cells and the production of chemokines between interleukin-6
      deficient and wild-type mice following 0, 1.0, or 3.0 mg diesel particles/m3
      diesel exhaust inhalation for 4 weeks. Exposure to diesel exhaust significantly
      increased the number of inflammatory cells and the amount of CCL17 and CXCL3 in
      bronchoalveolar lavage fluids from wild-type mice, but not in interleukin-6
      deficient mice. These findings suggest that interleukin-6 plays a critical role
      in airway inflammatory responses induced by diesel exhaust inhalation.

PMID- 17190746
TI  - Chemokine CXC receptor 4: an evolutionary approach.
AB  - Selected segments of the nucleotide sequences of the human 18S rRNA and the human
      formyl peptide receptor 1 mRNA exhibit structural similarities that are unlikely
      to be due simply to chance. Herein we analyze the structural similarities between
      the human 18S rRNA gene and the vertebrate chemokine CXC receptor 4 (CXCR4) gene
      that encodes a class A (rhodopsin-like) seven-transmembrane G-protein coupled
      receptor belonging to the same superfamily of formyl peptide receptors. The
      method of study was based on the recording of the positions of the 7-or-more-base
      oligonucleotide identities encountered in the 18S and CXCR4 genes and the
      construction of scatter-plots (abscissa-18S; ordinate-CXCR4) displaying the
      identity points positions. Analysis of the distribution of distances between
      identity points (abscissa-ordinate in the scatter-plot) demonstrated distinct
      peaks of frequency around 1200. Series of identities arranged near diagonal lines
      at 45 degrees in the scatter-plot (quasialignments) were evaluated for their
      probabilistic level of random occurrence. Results of this analysis demonstrated
      nonrandom quasialignments between (i) a 900-nt ca. section of the human CXCR4
      intron that immediately precedes almost the whole of the coding sequence and the
      18S gene from nt 125 to 1025 ca.; and (ii) a 425-nt ca. section of the CXCR4
      vertebrate genes, corresponding to nt 137-560 of the coding sequence, and the 18S
      gene from nt 1300 to 1730 ca. In both instances significant quasialignments are
      evidenced when CXCR4 nt sequences are shifted to the right by about 1200 nt with
      respect to the 18S nt sequence, as confirmed by analysis of the abscissa -
      ordinate differences. Taken together, these results indicate that, at least in
      humans, a continuous nonrandom quasialignment extends for some 1600 nt, from the
      second part of the (single) intron to the first part of the coding sequence. We
      hypothesize that the relatively more recent CXCR4 vertebrate gene might be
      evolutionarily related to the more ancient and highly conserved 18S gene.

PMID- 17190747
TI  - Visual recognition and visually guided action after early bilateral lesion of
      occipital cortex: a behavioral study of a 4.6-year-old girl.
AB  - We report the case of a 4.6-year-old girl born pre-term with early bilateral
      occipital damage. It was revealed that the child had non-severely impaired basic
      visual abilities and ocular motility, a selective perceptual deficit of figure
      ground segregation, impaired visual recognition and abnormal navigating through
      space. Even if the child's visual functioning was not optimal, this was the
      expression of adaptive anatomic and functional brain modifications that occurred
      following the early lesion. Anatomic brain structure was studied with anatomic
      MRI and Diffusor Tensor Imaging (DTI)-MRI. This behavioral study may provide an
      important contribution to understanding the impact of an early lesion of the
      visual system on the development of visual functions and on the immature brain's
      potential for reorganisation related to when the damage occurred.

PMID- 17190748
TI  - Abnormal reactivity of the primary somatosensory cortex during the experience of
      pain in complex regional pain syndrome: a magnetoencephalograhic case study.
AB  - A 49-year-old male worker developed persistent pain in his left wrist after work
      strain injuries. Clinical symptoms met with criteria for Complex Regional Pain
      Syndrome (CRPS) type I. In the present study, the effect of the experience of
      pain on the somatotopy of the primary cortical hand representation was
      investigated. Somatosensory evoked magnetic fields (SEF) elicited by non-painful
      tactile stimulation at the index finger of the affected and the unaffected hand
      were recorded when experiencing pain elicited by a moderate physical load
      condition (holding a 1.6 kg object in the hand). It was shown that MEG and
      subjective responses to innocuous tactile stimuli were reduced when simultaneous
      nociceptive stimulation was applied. These findings suggest a gating effect in
      the central nervous system elicited by concurrent simultaneous information from
      two different somatosensory modalities (pain and tactile). The results revealed
      the existence of nociceptive-induced plastic changes in the central nervous
      system associated with CRPS type I.

PMID- 17190749
TI  - Abnormal configural face perception in a patient with right anterior temporal
      lobe atrophy.
AB  - Face perception is a vital aspect of human social functioning and involves
      specialized cognitive and neural mechanisms. For example, configural face
      processing involves determining the relationship between the parts of the face,
      and this process enables us to differentiate between different faces. Here, we
      report an unusual case in which right anterior temporal lobe atrophy resulted in
      a profound deficit in the ability to recognize faces. We demonstrate that this
      patient is not able to process faces via configural information, raising the
      possibility that the right anterior temporal lobe has a role in configural face
      processing.

PMID- 17190750
TI  - Highly functional ipsilateral motor control after extensive left hemispheric
      damage during gestation.
AB  - In large early cortical lesions, one of the most devastating consequences is the
      impaired motor dexterity of the contralateral limb. We present the case of an 8
      year-old girl with a large left hemispherical porencephaly. Unlike previous
      reports, the girl exhibited high dexterity of the contralateral hand with
      preserved independent finger movements. We performed functional MRI of hand motor
      functions and diffusion tensor imaging, which revealed activation of the
      ipsilateral motor cortex and absence of a contralateral corticospinal tract.
      These observations suggest that by intensive training in early life, a complete
      transhemispheric shift of motor control with high skills can be achieved.

PMID- 17190751
TI  - Primary progressive aphasia in a bilingual woman.
AB  - Multilingual aphasias are common because most people in the world know more than
      one language, but little is known of these syndromes except in patients who have
      had a stroke. We present a 76-year-old right-handed woman, fluent in English and
      Chinese, who developed anomia at age 70 and then progressed to aphasia.
      Functional neuroimaging disclosed mild left temporoparietal hypometabolism.
      Neurolinguistic testing was performed in both English and Chinese, representing a
      unique contribution to the literature. Results revealed conduction-like aphasia
      that was comparable in the two languages, although English was slightly better
      preserved. Primary progressive aphasia has disrupted 2 languages in a similar
      manner, suggesting their close neuroanatomic relationship in this case.

PMID- 17190752
TI  - Afferent contributions to digit force coupling and force level variation during
      performance of non-lift pinch.
AB  - Afferent contributions to the coordination of thumb and index finger forces
      during non-lift pinch were studied using an anesthetization case study design.
      Two subjects, one performing with and without digital anesthetization and one
      with intact sensation, produced dynamic pinch forces against a stable object,
      with and without visual feedback. Error corrections were less frequent post
      anesthetization, and the cross correlation between digit forces was lower when
      sensation was removed. However, this decrease in cross correlation between digit
      forces seemed to reflect a loss in the magnitude of tightly coupled error
      corrections when sensation was removed, rather than more frequent deviations of
      force magnitude between the digit forces. Force-time output without visual
      feedback lacked these error corrections, and the correlation between digit forces
      remained high, irrespective of sensory status. Additionally, with vision
      occluded, the time rate of force change did not vary in a gradual manner as would
      be expected from a neural representation of a sinusoidal target, but was instead
      marked by sudden abrupt reversals of force rate of change, invariant of
      somatosensory status. The coupling of digit forces and rates of force change
      during non-lift pinch appear to be controlled primarily with feedforward
      mechanisms, where the lack of proprioceptive feedback does not seem to disrupt
      this coupling.

PMID- 17190753
TI  - A case of impaired naming and knowledge of body parts. Are limbs a separate sub
      category?
AB  - A left hemisphere stroke patient presented a disproportionate difficulty for body
      parts knowledge without autotopagnosia. The deficit concerned the lexical
      semantic representation of body parts and was most severe for limbs. The ability
      to gesture was spared and action naming was not more impaired than object naming.
      On the basis of normal naming latencies, we conclude that limbs are the most
      vulnerable component of the overall category of body parts. This vulnerability is
      not explained by unbalanced nuisance variables. More cognitive effort is probably
      required for the appropriate differentiation of limbs during semantic processing
      and lexical access.

PMID- 17190755
TI  - Importance of atrophic gastritis in diagnostics and prevention of gastric cancer:
      application of plasma biomarkers.

PMID- 17190756
TI  - Palliative treatment of malignant dysphagia with self-expanding metal stents: a
      12-year experience.
AB  - OBJECTIVE: The incidence of oesophageal cancer is increasing but the prognosis is
      still very poor. Around 50% of patients have advanced disease when diagnosed.
      Stenting using expandable metal stents is primarily aimed at palliation. The
      purpose of this study was to evaluate factors influencing morbidity, procedure
      related mortality and symptom relief for dysphagia in patients with unresectable
      oesophageal cancer treated with self-expanding metal stents. MATERIAL AND
      METHODS: We conducted a retrospective observational clinical study of consecutive
      patients treated with self-expanding metal stents in the Department of Surgery,
      Danderyd Hospital, Sweden, between January 1993 and May 2005. RESULTS: One
      hundred and seventy-four stents were placed in 149 patients. The procedure
      related mortality was 3% and the complication rate 26%. Pre- and post-treatment
      dysphagia could be evaluated in 139 stent placements, and showed significant
      improvement of dysphagia symptoms in 70% of subjects (p<0.0001). Tumour length,
      tumour location, histology, age, gender or prior dilatation did not affect the
      outcome regarding procedure-related morbidity or symptom relief. CONCLUSIONS:
      Palliation of malignant dysphagia with self-expanding metal stents is safe and
      confers almost immediate improvement of dysphagia in the majority of patients.
      Tumour-related and demographic factors do not seem to influence the outcome.

PMID- 17190757
TI  - Rising incidence of clinically evident Barrett's oesophagus in The Netherlands: a
      nation-wide registry of pathology reports.
AB  - OBJECTIVE: The incidence of oesophageal adenocarcinoma has increased steadily
      over the past few decades, but little information is available on trends in the
      incidence of its presumed precursor, Barrett's oesophagus (BO). MATERIAL AND
      METHODS: The nation-wide registry of pathology reports (PALGA) was used to
      investigate time trends in the incidence of BO in The Netherlands. Standardized
      morbidity ratios (SMRs) were calculated to examine the magnitude of the changes.
      RESULTS: The study comprised 105,283 patients with a first-time biopsy taken from
      the oesophagus. Of these patients, 33,365 had BO, 6168 squamous cell carcinoma
      and 9854 had adenocarcinoma of the oesophagus, diagnosed between 1992 and 2003.
      The age-adjusted incidence of BO increased among men by 41% (95% confidence
      interval (CI) 38-44%). Among women, the increase was 23% (CI 19-26%) in 1996-99,
      followed by a slight decline in 2000-03. The increase was most notable among
      younger patients (<60 years), whereas the incidence remained stable among men and
      decreased among women aged 75 or older. Although the number of oesophageal
      biopsies increased by 21% among men and by 6% among women, the proportion of
      biopsies with a diagnosis of BO increased to a larger extent, by 33% (CI 30-36%)
      for men and by 25% (CI 22-29%) for women. The incidence of adenocarcinoma of the
      oesophagus increased by 28% for men and by 22% for women. CONCLUSIONS: Our
      findings show a significant increase in the incidence of clinically evident BO.
      Although changes in endoscopic practice may partly explain these findings, a true
      increase in the incidence of BO seems likely.

PMID- 17190758
TI  - High recurrence rate of Barrett's epithelium during long-term follow-up after
      argon plasma coagulation.
AB  - OBJECTIVE: Several studies have shown that argon plasma coagulation (APC)
      combined with proton-pump inhibitor (PPI) therapy is a suitable procedure to
      eradicate Barrett's epithelium for a short-term follow-up. The real impact of
      this kind of management with respect to cancer risk and durability of squamous
      regeneration remains unclear. We present the follow-up data for up to 51 months
      after eradication of Barrett's mucosa. MATERIAL AND METHODS: In 1998-2001, 25
      patients with Barrett's esophagus were included in a prospective study. After
      baseline documentation, Barrett's epithelium was treated with repeated APC until
      complete squamous restoration was reached. Thereafter, all patients were
      continuously treated with high-dose PPIs. RESULTS: Each patient underwent a
      median of four APC sessions. Twenty-one (84%) of the patients had complete
      squamous regeneration at the end of treatment. During a follow-up of up to 51
      months, Barrett's epithelium was found to have recurred in 14/21 (66%) patients.
      Including the patients with initially incomplete squamous restoration, a long
      lasting and complete effect was achieved in only 7 patients (28%) after a mean
      follow-up period of 30 months. CONCLUSIONS: So far, it is still not proven
      whether coagulation-induced squamous regeneration reduces the risk of Barrett's
      carcinoma. Furthermore, the high relapse rate, the procedure-related risk, and
      the high costs incurred preclude the routine use of APC for the treatment of non
      dysplastic Barrett's esophagus. The different recurrence rates between published
      studies may be due to technical differences and PPI schedule. We suggest that
      optimal conditions for the procedure must be defined before further studies are
      undertaken.

PMID- 17190759
TI  - The antagonistic metabolite of GLP-1, GLP-1 (9-36)amide, does not influence
      gastric emptying and hunger sensations in man.
AB  - OBJECTIVE: Glucagon-like peptide-1 (GLP-1 (7-36)amide) is an intestinal hormone
      that is released in response to meal ingestion. GLP-1 reduces postprandial
      gastric and exocrine pancreatic secretion and is believed to inhibit gastric
      emptying. Furthermore, GLP-1 may play a role in hunger and thirst regulation. In
      vivo, GLP-1 is rapidly (within minutes) converted into a metabolite, GLP-1 (9
      36)amide, which has been shown to act as a GLP-1 receptor antagonist in vitro and
      in anaesthetized pigs. The purpose of this study was to assess the effect of
      infusion of GLP-1 (9-36)amide on hunger ratings and antral emptying of a meal.
      MATERIAL AND METHODS: Six healthy volunteers were tested in a double-blind,
      placebo-controlled fashion. Antral emptying of a liquid meal and hunger ratings
      were determined using ultrasound technology and visual analogue scale scoring
      during infusions of saline or GLP-1 (9-36)amide (5 pmol/kg body wt/min) resulting
      in supraphysiological concentrations. RESULTS: Infusion of GLP-1 (9-36)amide had
      no effect on gastric emptying or the sensation of hunger compared to saline.
      CONCLUSIONS: Our findings suggests that the rapid formation of the antagonistic
      metabolite does not influence gastric emptying and hunger ratings in humans even
      when it is present in supraphysiological concentrations.

PMID- 17190760
TI  - Liquid and solid gastric emptying in adults treated for Hirschsprung's disease
      during early childhood.
AB  - OBJECTIVE: Dysmotility of the upper gastrointestinal tract has been reported in
      children with Hirschsprung's disease. In the present study, gastric emptying was
      studied in adult patients with Hirschsprung's disease to elucidate whether there
      is a persisting involvement of the upper gastrointestinal tract in this group of
      patients. MATERIAL AND METHODS: Gastric emptying of caloric liquids and solids
      was studied in 16 adult patients with surgically treated Hirschsprung's disease
      during early childhood and in age-matched controls. To examine liquid emptying,
      the paracetamol absorption test was applied using a meal containing glucose,
      lactose, maize oil, water (2020 kJ) and paracetamol. To examine solid emptying,
      the 13C gastric emptying breath test was applied using a meal containing white
      bread, margarine, a one-egg omelette (1050 kJ) and [13C]-octanoic acid.
      Gastrointestinal symptoms were recorded according to a standardized
      questionnaire. RESULTS: For liquid meal emptying, the time until emptying
      commenced was 8.1+/-1.9 and 2.9+/-0.9 min (mean+/-SE) in patients and controls,
      respectively (p=0.02). Thereafter, the first 25% of the meal emptied in 6.8+/-0.8
      and 12.1+/-1.1 min in patients and controls, respectively (p=0.0005). The overall
      emptying rate tended to be delayed in patients compared with controls (p=0.06).
      For the solid meal, a delay in emptying was evident (p=0.02). The patients
      reported more symptoms from the upper gastrointestinal tract than the controls,
      but the symptoms were not significantly related to the emptying pathology
      demonstrated. CONCLUSIONS: The present study demonstrates that adult patients
      with Hirschsprung's disease have an abnormal pattern of gastric emptying,
      indicating persisting involvement of the upper gastrointestinal tract.

PMID- 17190761
TI  - Conservative treatment of acute colonic diverticulitis: are antibiotics always
      mandatory?
AB  - OBJECTIVE: Most patients admitted for acute colonic diverticulitis (AD) are
      managed conservatively and receive antibiotics, although it is uncertain whether
      all patients with AD benefit from this treatment. The aim of this study was to
      evaluate the influence of antibiotic treatment on outcome in the conservative
      management of patients with mild AD. MATERIAL AND METHODS: A retrospective audit
      of 311 patients (64% F, mean age 60 years) hospitalized for AD was carried out.
      All patients were initially treated conservatively with observation and
      restriction of oral intake. Patients receiving antibiotics (n=118) were compared
      with patients treated with observation and restriction of oral intake only
      (n=193). Mean follow-up time (FU) was 30 months. RESULTS: Inflammation in
      patients treated with antibiotics was more pronounced (laboratory parameters (C
      reactive protein, white blood cell count) were higher (p<0.01), fever was more
      common (p<0.01) and CT grading of inflammation was classified as severe in a
      higher proportion (p<0.01)) compared with patients treated without antibiotics.
      When initially treated with antibiotics, 3 patients (3%) failed to respond to
      treatment and had to undergo surgery. There were 7 (4%) failures in patients
      initially treated without antibiotics, and antibiotics were then added. During
      FU, 29% of patients treated with antibiotics had further events (recurrent AD
      and/or subsequent surgery) compared with 28% (NS) among those treated without
      antibiotics. In a multivariate analysis, the risk of a further event was not
      influenced by antibiotic treatment (OR 1.03, CI 95% 0.61-1.74). CONCLUSIONS: Our
      results indicate that antibiotics are not mandatory in mild AD. Treatment without
      antibiotics appears to be safe and seems not to change the rate of further
      events. These results warrant further randomized prospective studies.

PMID- 17190762
TI  - HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac
      disease.
AB  - OBJECTIVE: Celiac disease (CD) is a T-lymphocyte-mediated small intestinal
      enteropathy triggered and maintained by dietary gluten, with a strong genetic
      component mapping to the HLA genes encoding for the class II DQ(alpha1*0501,
      beta1*02) molecule. Damage of the small intestine may cause a variety of clinical
      signs ranging from isolated long-standing iron-deficiency anemia refractory to
      iron supplementation to forms of severe malnutrition that may become life
      threatening. However, patients carrying the typical intestinal lesions of CD and
      presenting no symptoms at all (silent CD) are also a common clinical observation.
      Since it is commonly assumed that clinical signs and symptoms tend to correlate
      with the severity of the intestinal damage, the purpose of this study was to
      investigate whether particular HLA class II genotypes might also influence the
      extent of intestinal damage and consequently the clinical presentation of the
      disease. MATERIAL AND METHODS: We retrospectively compared histological grading
      of celiac disease intestinal biopsies with HLA haplotype, age at onset of disease
      and clinical signs and symptoms. RESULTS: Our findings showed that homozygosis
      for the DQB1*0201 allele is associated with a higher severity of the histological
      score (p<0.008). Of note for the clinician, this work also suggests that the same
      type 3c of intestinal damage causes a different clinical syndrome, depending on
      the patient's age. CONCLUSIONS: The genetic predisposition at the HLA-DQB1 locus
      influences the severity of the mucosal damage in a dose-dependent manner, but not
      the clinical presentation, of celiac disease.

PMID- 17190763
TI  - No observed local immunological response at cell level after five years of oats
      in adult coeliac disease.
AB  - OBJECTIVE: Our earlier 5-year follow-up study produced the first evidence to show
      the long-term safety of oats as part of a coeliac diet. The objective of the
      present study was to clarify its applicability by analysing local cellular
      immunological responses after 5 years' consumption of oats by adult coeliac
      patients. MATERIAL AND METHODS: Forty-two coeliac patients took part in an
      earlier oats intervention study for 6-12 months. Twenty-two of these patients
      originally consumed oats as part of their gluten-free diet. During the 5-year
      follow-up 10 patients had felt uncertain about the safety of long-term
      consumption of oats and gave up this part of their diet. Finally, 12 of the 22
      patients consumed oats for the whole 5-year period. The control group consisted
      of the remaining 20 coeliac patients using a strict, conventional, gluten-free
      diet without oats. Intraepithelial CD3, alphabetaTCR (alphabetaIEL) and
      gammadeltaTCR (gammadeltaIEL) T cells were counted after specific staining of
      small intestinal biopsy specimens. RESULTS: There were no differences in the
      densities of CD3, alphabetaIEL and gammadeltaIEL T cells between the oat and the
      control groups. CONCLUSIONS: Long-term use of oats included in the gluten-free
      diets of patients with coeliac disease does not stimulate an immunological
      response locally in the mucosa of the small intestine.

PMID- 17190765
TI  - Attendance at surveillance endoscopy of patients with adenoma or colorectal
      cancer.
AB  - OBJECTIVE: Surveillance of patients treated for adenoma or colorectal cancer
      (CRC) is intended to reduce the incidence of CRC. Responsibility for the
      adherence to surveillance advice is often left to the patients and family
      physician. It is not known whether this type of passive policy affects the
      efficacy of surveillance. The aim of this study was to determine the yield of
      surveillance without active invitation to follow-up endoscopy. MATERIAL AND
      METHODS: The study comprised a cohort follow-up of patients under 75 years of age
      with adenomas or CRC at index endoscopy in the period 1997-99. Adherence and
      intervals of follow-up endoscopy were determined up to December 2004. RESULTS:
      During the inclusion period 2946 patients underwent lower endoscopy. In total,
      393 patients were newly diagnosed with colorectal polyps (n=280) or CRC (n=113).
      Polyps were classified as adenomas in 167/280 (61%) patients. Forty-five (27%) of
      the adenoma patients underwent surveillance endoscopy within the guideline
      interval, 63 (38%) underwent delayed endoscopy, and 59 (35%) did not have any
      follow-up at all. CRC was diagnosed in 113 patients. Thirty-six patients who died
      during the first year or were diagnosed with metastases were excluded from the
      analysis. Twenty-three (30%) of the remaining 77 patients underwent endoscopic
      surveillance according to the guidelines, 40 (52%) had delayed surveillance
      endoscopy, and 14/77 (18%) did not undergo surveillance endoscopy at all.
      CONCLUSIONS: In surveillance for colorectal neoplasia, active follow-up
      invitation is important. Given the low follow-up rate in our series, passive
      follow-up policies may lead to under-performance of surveillance programs. An
      active and controlled follow-up is advisable.

PMID- 17190764
TI  - Undiagnosed coeliac disease and nutritional deficiencies in adults screened in
      primary health care.
AB  - OBJECTIVE: To compare the nutritional parameters of individuals with a previous
      diagnosis of coeliac disease (CD) with those of screen-detected patients in a
      large cohort of adults in primary care. MATERIAL AND METHODS: A cohort of 1900
      adults (aged 18-64 years) was screened for tissue transglutaminase antibodies
      (TG2A) in primary care in the capital region of Finland. IgA-endomysium
      antibodies (EmA), HLADQ2/8 associated with CD were determined in positive
      individuals. Folate, iron, and transferrin receptor in sera were assessed in
      patients reporting a previous diagnosis of CD and patients positive for the above
      tests. RESULTS: Twenty-two out of 1900 (1%) patients reported a previous
      diagnosis of CD (biopsy-based 16/22 cases; 6/22 cases diagnostic criteria
      unknown). Among the screen-detected cases with TG2A> or = the cut-off value,
      14/32 cases were considered to have CD based on high levels of both TG2A and EmA,
      DQ2/8 genotype and/or biopsy results. The prevalence of CD was as high as 1:53 in
      the total study population (36/1900), and in women even 1:46 (2.2%). Nutritional
      deficiencies were rare among CD patients diagnosed earlier (low iron = 1; low
      folate n=1) but common among those who had an undiagnosed CD (low folate n=6;
      p<0.005; concomitant iron deficiency n=2). One-third of the screen-detected CD
      patients were obese. Screen-detected patients did not present more abdominal
      symptoms than those with no CD. CONCLUSIONS: CD is common, the proportion among
      women possibly being as high as 2.2%. Although the great majority of screen
      detected patients do not present any gastrointestinal symptoms at primary care,
      nutritional deficiencies such as low folate levels and iron deficiency are
      common.

PMID- 17190766
TI  - Effect of azoxymethane and curcumin on transcriptional levels of cyclooxygenase-1
      and -2 during initiation of colon carcinogenesis.
AB  - BACKGROUND: Curcumin is well documented as an effective colonic chemopreventive
      agent in preclinical studies. Inhibition of arachidonic acid metabolism has been
      considered one of anticarcinogenic mechanisms of curcumin. We recently reported
      resistance of middle-aged F344 male rats to inhibition of azoxymethane (AOM)
      induced colonic aberrant crypt foci (ACF) by curcumin (Nutr Cancer, 48, 37-43).
      It was important to confirm this finding and to find potential mechanisms
      responsible, as loss of preventive activity of curcumin due to aging was a novel
      finding, with important implications for human intervention trials. METHODS: To
      confirm our previous findings, and investigate arachidonic acid metabolism as a
      potential mechanism of age-related differences in response to curcumin, middle
      aged F344 male rats were given AOM injections after being fed their experimental
      diets, 0.6% curcumin or control diet. Colonic ACF were evaluated and colonic
      levels of cyclooxygenase (COX)-1 and 2 mRNA and prostaglandin E2 (PGE2) were
      measured. Next, we investigated the short-term effect of AOM and curcumin on
      arachidonic acid metabolism in young rats. Six week-old rats were given
      injections of either AOM or untreated following their experimental diets. Colonic
      COX-1 and COX-2 mRNA as well as PGE2 levels were measured shortly after AOM
      treatment. Lastly, three different ages of F344 rats were treated with either AOM
      or saline, and colonic COX-1 and COX-2 mRNA levels were measured shortly after
      the injections to find if aging alters the effect of AOM on COX mRNA expression.
      RESULTS: In middle-aged rats, dietary curcumin did not reduce the number of ACF
      and surprisingly increased colonic levels of COX-2 mRNA. Colonic COX-2 and PGE2
      levels were also significantly increased in young rats fed curcumin after AOM
      injections. Interestingly, AOM did not affect COX-2 but decreased COX-1
      expression in all ages. CONCLUSIONS: Our study suggests that during initiation,
      AOM inhibits colonic COX-1 expression without affecting COX-2 and dietary
      curcumin may increase COX-2 expression to compensate AOM-induced reduction of COX
      1 expression.

PMID- 17190767
TI  - Rotavirus infections in paediatric oncology patients: a matched-pairs analysis.
AB  - OBJECTIVE: To conduct a systematic investigation of the clinical relevance of
      rotavirus infection in the setting of paediatric cancer patients receiving
      intensive chemotherapy. MATERIAL AND METHODS: Twenty-eight paediatric cancer
      patients with positive rotavirus antigen tests were eligible for a retrospective
      case-control study (January 1995-December 2004). Rota-positive patients were
      compared with 28 rota-negative patients matched for age, underlying disease and
      chemotherapy. The National Cancer Institute Common Toxicity Criteria were used to
      determine clinical severity. RESULTS: Median duration of rota-related symptoms
      (diarrhoea, fever and vomiting) was 7 days (range 4-34 days; 75th percentile 9
      days). Median duration of viral shedding was 17 days (4-73 days; 75th percentile
      39.5 days). The rota infection was nosocomially acquired in 19 patients (68%).
      The proportions of patients with diarrhoea > or =NCI II, fever >39 degrees C,
      clinically relevant dehydration, metabolic acidosis, mucositis and neutropenia
      were significantly higher in rota-positive patients. Rota-positive patients
      tended to have a prolonged period of hospitalization (median 8 versus 4 days;
      p=0.008). A higher proportion of rota-positive patients had to receive parenteral
      nutrition and tube feeding (p<0.001). CONCLUSIONS: Rotavirus is a clinically
      relevant but preventable pathogen in paediatric cancer patients, since many cases
      seem to be nosocomial in origin. Rapid microbiological testing and contact
      precautions should be strictly applied to any symptomatic patient and to their
      immediate contacts. Prolonged viral shedding in immunocompromised paediatric
      patients necessitates repeated testing in order to determine the duration of
      isolation.

PMID- 17190768
TI  - Changes over a 20-year period in the clinical presentation of primary sclerosing
      cholangitis in Sweden.
AB  - OBJECTIVE: The use of magnetic resonance cholangiopancreaticography (MRCP) as a
      non-invasive diagnostic tool for primary sclerosing cholangitis (PSC), together
      with increased clinical awareness of the disease, has led to earlier diagnosis.
      The aim of this study was to investigate the clinical presentation of PSC
      including its association with inflammatory bowel disease (IBD) and the
      development of cholangiocarcinoma at one centre over an observation period of 20
      years. MATERIAL AND METHODS: All patients with well-defined PSC, diagnosed after
      16 years of age and treated at Huddinge University Hospital between 1984 and
      2004, were included in the study (n=246). PSC and IBD characteristics were
      retrieved from the patients' medical records. The patients were subdivided
      according to the date of diagnosis: 185 PSC patients diagnosed before 30 October
      1998 were compared with 61 patients diagnosed after that date. RESULTS: Patients
      diagnosed after 1998 were significantly older at diagnosis (mean age 41 versus 37
      years) and presented fewer symptoms (47% versus 63%) as well as a lower frequency
      of coexisting IBD (69% versus 82%). In the whole group, women had significantly
      more symptoms than men, particularly pruritus (p<0.05). CONCLUSIONS: The clinical
      spectrum of PSC in Sweden has changed over the past 20 years; today, PSC patients
      are older at diagnosis and associated IBD is less frequent.

PMID- 17190769
TI  - Inflammatory response in patients with malignant obstructive jaundice.
AB  - OBJECTIVE: Surgery in patients with malignant obstructive jaundice is associated
      with increased risks for postoperative septic complications. The aim of this
      study was to investigate the inflammatory and the local cellular immune response
      in patients accepted for surgery because of tumours in the hepatic-pancreatic
      biliary (HPB) tract. MATERIAL AND METHODS: Patients with obstructive jaundice
      (group HPB(+)) were compared with those without (HPB(-)). Patients undergoing
      surgery for benign abdominal disorders served as controls. Obstructive jaundice
      was present in 18 out of 33 HPB patients. Preoperatively, blood was analysed for
      bacteria, endotoxins and cytokines (TNF-alpha, IL-6 and IL-10). At operation,
      mesenteric lymph nodes (MLNs) were excised for bacterial cultures using standard
      microbiological techniques, and immunohistochemistry, using antibodies CD4 and
      CD8 (mainly staining T lymphocytes), CD68 (macrophages), and anti-caspase-3 (to
      determine the rate of apoptosis). RESULTS: Bacterial translocation was not
      demonstrated in any of the patients. Increased preoperative concentrations of
      endotoxins were found in group HPB(+). The number of macrophages and the rate of
      apoptosis in MLNs were increased in jaundiced patients, while the number of T
      lymphocytes was decreased. CONCLUSIONS: Malignant obstructive jaundice causes
      increased blood concentrations of endotoxins and cytokines, an increased number
      of macrophages in MLNs, a higher rate of apoptosis in MLNs, but a decreased
      number of T lymphocytes in MLNs. The lymphocyte depletion is probably due to the
      increased rate of apoptosis, and might reduce the ability of jaundiced patients
      to eradicate infection.

PMID- 17190770
TI  - Apoptosis, proliferation and differentiation patterns are influenced by
      Zebularine and SAHA in pancreatic cancer models.
AB  - OBJECTIVE: Pancreatic cancer continues to be an urgent clinical problem. We used
      the novel DNA methyltransferase inhibitor Zebularine and the histone deacetylase
      inhibitor SAHA to investigate the epigenetic influence on viability and
      differentiation of the pancreatic cancer cell lines YAP C, DAN G and Panc-89 in
      vitro and in vivo. MATERIAL AND METHODS: Cell vitality, proliferation and
      expression of PDX-1, cytokeratin 7 and 20, chromogranin A, vimentin, bax and bcl
      2 were determined on the protein and mRNA level in vitro and in a subcutaneous
      xenograft model. RESULTS: A time- and dose-dependent increase of apoptosis,
      paralleled by decreased proliferation, was observed after incubation with single
      agents or a combination therapy with lower concentrations. This was associated
      with up-regulation of pro-apoptotic bax and a phenotypic stabilization by the
      enhanced expression of cytokeratin 7. In vivo, growth of xenografts was delayed
      with the most pronounced effect in Panc-89 after 1 week of daily intraperitoneal
      injections of Zebularine paralleled with CK7 up-regulation and down-regulation of
      dedifferentiation markers. CONCLUSIONS: Epigenetic modulation via inhibition of
      DNA methyltransferase and histone deacetylase induces apoptosis in human
      pancreatic cancer cells in vitro and delays xenograft growth in vivo, which is
      associated with a morphological/molecular phenotypic stabilization. These
      compounds may therefore be suitable as adjunctive therapeutic agents in the
      treatment of pancreatic cancer.

PMID- 17190771
TI  - Endoscopic ultrasound (EUS)-guided Trucut biopsy adds significant information to
      EUS-guided fine-needle aspiration in selected patients: a prospective study.
AB  - OBJECTIVE: Endoscopic ultrasound (EUS)-guided Trucut biopsy (EUS-TCB) has
      recently emerged as a method that seeks to overcome the limitations of EUS-guided
      fine needle aspiration (EUS-FNA) by providing a core-tissue specimen needed to
      increase the yield and accuracy of the diagnosis. The aim of our study was to
      evaluate whether EUS-TCB adds any information to EUS-FNA in selected patients and
      to assess the diagnostic yield, overall accuracy and complications of EUS-TCB as
      compared with EUS-FNA. MATERIAL AND METHODS: The study prospectively included 30
      patients who had undergone both procedures. RESULTS: The yield of adequate tissue
      harvesting was similar for EUS-FNA and EUS-TCB (96.4% versus 89.3%, p=NS), with
      the same number of passes done. The diagnostic accuracy of EUS-FNA was also
      similar to that of EUS-TCB for the diagnosis of malignant mediastinal masses
      (73.7% versus 68.4%, p=NS). However, the accuracy for obtaining a specific
      diagnosis was significantly lower for EUS-FNA compared with EUS-TCB (5.3% and
      68.4%, p<0.005). EUS-TCB did not appear to help as a rescue procedure in
      mediastinal tumours, after a false negative result of EUS-FNA. All cases of
      submucosal tumours were correctly classified by EUS-TCB as gastrointestinal
      stromal cell tumours (GISTs) or leiomyomas, while EUS-FNA raised only a suspicion
      of mesenchymal tumour. CONCLUSIONS: EUS-TCB was certainly useful when
      immunohistochemistry was needed, for example in submucosal tumours and lymphoma,
      as well as to confirm and characterize the primary or metastatic origin of
      mediastinal masses. The information provided by EUS-FNA and EUS-TCB is
      complementary, especially in selected cases where a complete histological
      diagnosis has an important impact on the clinical management.

PMID- 17190772
TI  - Variations in colonoscopy practice in Europe: a multicentre descriptive study
      (EPAGE).
AB  - OBJECTIVE: The volume of colonoscopies performed is increasing and differences in
      colonoscopy practice over time and between centres have been reported.
      Examination of current practice is important for bench-marking quality. The
      objective of this study was to examine variations in colonoscopy practice in
      endoscopy centres internationally. MATERIAL AND METHODS: This observational study
      prospectively included consecutive patients referred for colonoscopy from 21
      centres in 11 countries. Patient, procedure and centre characteristics were
      collected through questionnaires. Descriptive statistics were performed and the
      variation between centres while controlling for case-mix was examined. RESULTS: A
      total of 6004 patients were included in the study. Most colonoscopies (93%; range
      between centres 70-100%) were performed for diagnostic purposes. The proportion
      of main indications for colonoscopy showed wide variations between centres, the
      two most common indications, surveillance and haematochezia, ranging between 7
      24% and 5-38%, respectively. High-quality cleansing occurred in 74% (range 51
      94%) of patients, and 30% (range 0-100%) of patients received deep sedation.
      Three-quarters (range 0-100%) of the patients were monitored during colonoscopy,
      and one-quarter (range 14-35%) underwent polypectomy. Colonoscopy was complete in
      89% (range 69-98%) of patients and the median total duration was 20 min (range of
      centre medians 15-30 min). The variation between centres was not reduced when
      case-mix was controlled for. CONCLUSIONS: This study documented wide variations
      in colonoscopy practice between centres. Controlling for case-mix did not remove
      these variations, indicating that centre and procedure characteristics play a
      role. Centres generally were within the existing guidelines, although there is
      still some work to be done to ensure that all centres attain the goal of
      providing high-quality colonoscopy.

PMID- 17190773
TI  - Acute esophageal and gastric injury: complication of Lugol's solution.
AB  - Several new technologies have been developed to improve the diagnostic capability
      of conventional endoscopic techniques. One of these most frequently used methods
      is chromoendoscopy with Lugol's solution in the esophagus to detect malignant
      lesions. This method has been used for several decades and is generally
      considered as a safe method, only a few cases of side effects having been
      reported. We describe a case of acute esophageal and gastric mucosal damage after
      application of Lugol's solution during endoscopy in an 84-year-old woman.
      Endoscopists should be aware of the potential for adverse reactions to iodine
      staining.

PMID- 17190774
TI  - Basic conditioning factors' influences on adolescents' healthy behaviors, self
      efficacy, and self-care.
AB  - This article reports a secondary statistical analysis of data from a study
      investigating the relationships among health-promoting self-care behaviors, self
      care self-efficacy, and self-care agency in an adolescent population (Callaghan,
      2005). The purpose of this study was to identify the influences of selected basic
      conditioning factors on the practice of healthy behaviors, self-efficacy beliefs,
      and ability for self-care in 256 adolescents. The research instruments used to
      collect data for this study include: Health-Promoting Lifestyle Profile II Scale;
      Self-Rated Abilities for Health Practices Scale; Exercise of Self-Care Agency
      Scale; demographic questionnaire assessing basic conditioning factors. The
      results of this analysis identified significant relationships between the
      following basic conditioning factors and adolescents' practice of healthy
      behaviors, self-efficacy of those behaviors, and self-care abilities: support
      system, adequate income, adequate living conditions, gender, routine practice of
      religion, and reported medical problems/disabilities. These findings can give
      adolescent health nurses direction in developing interventions that promote the
      self-care and health in this specific population.

PMID- 17190776
TI  - Looking at families in nursing research: strategies for study design.
AB  - Pediatric nurses have identified the importance of studying children within the
      context of their families. There have been calls for attention to the family as
      the focus of study and unit of analysis in nursing research. One of the most
      important strategies for designing a study that keeps the focus on the family is
      the maintenance of study integrity. All the strategic choices made by the
      researcher when developing the research design need to reflect the theoretical
      premises on which the study is built. Throughout the study design, components of
      well-constructed family research will demonstrate consistency with the overall
      conceptual framework.

PMID- 17190775
TI  - Screening for asthma: results from a rural cohort.
AB  - BACKGROUND: Asthma, the leading cause of chronic illness in children, must be
      managed in both the home and school environments. Identification of children who
      have risk factors associated with asthma is the first step toward achieving one
      of the Healthy People 2010 (2000) objectives, which identifies that 25 states
      will establish a system of surveillance to track asthma mortality, morbidity,
      access to care, and asthma management. PURPOSE: The purposes of this research
      were to: a) identify rural children who are at risk for asthma through written
      screening; b) assess parameters of respiratory health status of rural school-aged
      children as indicated by forced expiratory volume at l second (FEV1), forced
      vital capacity (FVC), peak expiratory flow (PEF), mean mid-expiratory flow
      (FEF(25-75)); and c) identify the number of rural school-aged children who sought
      and obtained follow-up from their primary health care provider and were given a
      definitive diagnosis of asthma. FRAMEWORK: The Vulnerable Populations Framework
      (Flaskerud and Winslow, 1998) was used to organize this study. METHODOLOGY: A
      prospective descriptive design was utilized for this research. RESULTS:
      Approximately 12% of the children screened were referred to their primary care
      provider (PCP) for follow-up care. Of these approximately half of the children
      were seen by their PCP. Barriers to seeking follow-up care were: a) the child was
      not symptomatic all the time, b) reluctance to be diagnosed with asthma, and c)
      others, such as cost and time. Children who were not well controlled identified
      that they ran out of medicine and their parents did not refill their
      prescription. CONCLUSION: Results from this descriptive study indicate that
      screening for asthma in school may be a way to identify those children who are at
      risk for asthma, and who are not diagnosed as well as those who are diagnosed
      with asthma but are not optimally managed. While many parents wanted their
      children to be screened, follow-up care was not critical to them. IMPLICATIONS:
      Nurses working in a school setting are in a prime position to help identify those
      children with signs and symptoms of asthma. In addition, use of written
      screenings with or without spirometry may be helpful in identifying children at
      risk for asthma. Further studies need to be undertaken to determine if written
      screening is as efficacious as spirometry for school and other ambulatory care
      settings.

PMID- 17190778
TI  - Health literacy - identification and response.

PMID- 17190779
TI  - Understanding consumers' health information preferences: development and
      validation of a brief screening instrument.
AB  - The impact of health communication is generally enhanced when it is targeted or
      tailored to the needs of a specific population or individual. In a segmentation
      analysis of the U.S adult population - using data from 2,636 respondents to a
      mail panel survey - we identified four segments of the adult population that vary
      significantly with regard to health information preferences based on their degree
      of engagement in health enhancement, and their degree of independence in health
      decision making. We also created a brief (10 item), easy-to-administer screening
      instrument that indicates into which segment people fall. The purpose of this
      article is to describe the segments, and the screening instrument, and to present
      initial tests of its validity. We believe this instrument offers a practical tool
      for differentiating motivationally coherent subgroups of the adult population
      with regard to their health information preferences, and therefore may have
      practical value in improving health communication and health services provision
      efforts. Additional research is needed to further validate the tool and test its
      utility in guiding the creation of targeted health messages and programs.

PMID- 17190780
TI  - Explaining the increase in condom use among South African young females.
AB  - Since 1998 South Africa has experienced stability in HIV prevalence among its 15
      to 19 year olds, and to a lesser extent among its 20 to 24 year olds. While a few
      studies point to behavioural change, mainly an increase in condom use, none has
      established the reasons. This article explores the influence of various
      information sources about AIDS upon the use of condoms among rural and urban
      South African young females, using the South Africa Demographic Health Survey of
      1998 (1998 SADHS), while controlling for various socioeconomic and cultural
      parameters. The results show that condom use among urban residents was positively
      correlated with mass media exposure, television as a source of information about
      AIDS, and the number of mass media sources from which the respondent received
      information about AIDS. Condom use among rural residents was associated with the
      number of sources of information about AIDS, exposure to mass media, and the
      language and education of the respondent. Among urban residents condom use was
      almost twice as high as among rural residents. The results from the article
      indicate that three elements influenced the increase in condom use among females:
      the threat of AIDS, mass media, and receptiveness to condom use. The
      receptiveness was culturally dependent.

PMID- 17190781
TI  - "Live and Let Live": an analysis of HIV/AIDS-related stigma and discrimination in
      international campaign posters.
AB  - As a corollary to The Declaration of Commitment adopted by the United Nations
      General Assembly Special Session on HIV/AIDS in June 2001, UNAIDS developed a
      World AIDS Campaign that sought to eradicate HIV/AIDS-related stigma and
      discrimination. The campaign incorporated several educational strategies,
      including a poster campaign that advocated the just and equal treatment of people
      living with HIV/AIDS. In an effort to develop an understanding of these
      educational efforts, this study deconstructs the 2002-2003 World AIDS Campaign
      posters. While the overall results suggest that the campaign has been successful
      in redefining images of HIV/AIDS, they also show that certain aspects of these
      posters may actually serve to reinforce stigma and discrimination. Using a visual
      studies approach to textual analysis, this study explores the underlying
      ideological and cultural assumptions that exist within the posters and provides a
      method for evaluating such materials.

PMID- 17190782
TI  - Changing smoking attitudes by strengthening weak antismoking beliefs - Taiwan as
      an example.
AB  - I first explored the strength of Taiwanese high school students' beliefs
      regarding five antismoking messages. Findings of a nationwide survey showed that
      the students held these beliefs in the following order of decreasing strength:
      second-hand smoke damages health, smoking has long-term health consequences,
      smoking has short-term health consequences, cigarette marketers are manipulative,
      and smokers are perceived negatively. Experiment one further showed that
      antismoking ads featuring weakly held beliefs are more effective than those
      featuring strongly held beliefs. Experiment two demonstrated that antismoking
      campaigns need to be framed carefully; in general, it is more effective to
      positively frame messages about strongly held antismoking beliefs but negatively
      frame messages about weakly held antismoking beliefs.

PMID- 17190783
TI  - Going beyond exposure to local news media: an information-processing examination
      of public perceptions of food safety.
AB  - The relationship between local news media and public perceptions of food safety
      was examined in a statewide telephone survey (n = 524). The theoretical framework
      of the study was based on a review of the social and psychological factors that
      affect public concerns about food safety, the relationship between mass
      communication and risk perception, and the thesis of information-processing
      strategies and its impact on learning from the news. The results show that
      information-processing strategies substantially mediated the relationship between
      local news media and public perceptions of food safety, with elaborative
      processing being more influential than active reflection in people's learning
      from the news media. Attention to local television had an independent effect,
      after demographics, awareness of food safety problems, and perceived safety of
      local food supply were statistically controlled. Other important predictors
      included gender, education, ethnicity, and perceived safety of local food supply.

PMID- 17190786
TI  - Antiviral signaling through pattern recognition receptors.
AB  - Viral infection is detected by the host innate immune system. Innate immune cells
      such as dendritic cells and macrophages detect nucleic acids derived from viruses
      through pattern recognition receptors (PRRs). Viral recognition by PRRs initiates
      the activation of signaling pathways that lead to production of type I interferon
      and inflammatory cytokines, which are important for the elimination of viruses.
      Two types of PRRs that recognize viral nucleic acids, Toll-like receptors (TLR)
      and RIG-I-like RNA helicases (RLH), have been identified. Of the TLRs, TLR3
      recognizes viral double-stranded (ds) RNA, TLR7 and human TLR8 identify viral
      single-stranded (ss) RNA and TLR9 detects viral DNA. TLRs are located in
      endosomal compartments, whereas RLH are present in the cytoplasm where they
      detect viral dsRNA or ssRNA. Here we review the role of TLRs and RLHs in the
      antiviral innate immune response.

PMID- 17190787
TI  - Characteristic expression of Lewis-antigenic glycolipids in human ovarian
      carcinoma-derived cells with anticancer drug-resistance.
AB  - By comparing ovarian carcinoma-derived KF28 cells with the corresponding
      anticancer drug-resistant cells, the taxol- and cisplatin-resistant properties
      were found to be closely related with MDR1 and BSEP, and MRP2 transporters,
      respectively. In addition to the transporters expression, the amounts of
      glycolipids, particularly their longer carbohydrate structures, in the resistant
      cells increased to 3-4-fold of those in the sensitive cells due to enhanced
      transcription of the respective glycosyltransferases. The major glycolipids in
      the sensitive and resistant cells were GlcCer and Gb(3)Cer, respectively, and
      extension of the carbohydrate structure into Lewis antigen characteristically
      occurred in the resistant cells. Le(b), which was not detected in the cisplatin
      resistant cells, was present in the taxol-resistant cells, while Le(x) was
      present in the cisplatin-resistant cells at a higher concentration than in the
      taxol-resistant cells. 2-Hydroxy fatty acids were significantly abundant in
      glycolipids of the resistant cells, but they were not detected in free ceramides
      or sphingomyelin, indicating that the enhanced synthesis of glycolipids in the
      resistant cells was not linked with the removal pathway for virulent ceramides
      derived from sphingomyelin. The resistant cells with abundant glycolipids
      exhibited lower membrane fluidity than the KF28 cells, and this property might be
      involved in the anticancer drug-resistance.

PMID- 17190788
TI  - A network analysis of changes in molecular interactions in cellular signaling.
AB  - Multiprotein complexes play an essential role in the propagation and integration
      of cellular signals. However, systems level analyses of signaling-dependent
      changes in the pattern of molecular interactions are still missing. Signaling in
      T-lymphocytes is one prominent example in which multiprotein complexes
      orchestrate signal transduction. We implemented peptide microarrays comprising a
      set of interaction motifs of signaling proteins for network-based analyses of
      signaling-dependent changes in molecular interactions. Lysates of resting or
      stimulated cells were incubated on these arrays, and the binding of signaling
      proteins was detected by immunofluorescence. Signaling-dependent complex
      formation led to changes of signals on the microarrays in two ways. 1) Masking of
      a binding site of a signaling protein for a peptide on the array resulted in a
      signal decrease. 2) Interaction of a protein with a second protein, which in turn
      binds to a peptide on the array, resulted in a signal increase for the first
      protein. Dissipation of complexes led to the reverse changes. Competition with
      peptides corresponding to interaction motifs provided detailed information on the
      architecture of complexes; lack of individual signaling proteins revealed the
      functional interdependence of interactions in the network. We show that complex
      formation through phosphorylation of the scaffolding protein LAT (linker for
      activation of T-cells) acted as a signal amplifier. PLCgamma1 deficiency
      increased the resting state levels of LAT-dependent complexes and augmented the
      recruitment of the phosphatase SHPTP2 into complexes. For the analysis of
      signaling networks, the parallel detection of changes in interactions enabled the
      identification of functional interdependencies with minimum a priori knowledge.

PMID- 17190789
TI  - The N-terminal domain of Tob55 has a receptor-like function in the biogenesis of
      mitochondrial beta-barrel proteins.
AB  - beta-Barrel proteins constitute a distinct class of mitochondrial outer membrane
      proteins. For import into mitochondria, their precursor forms engage the TOM
      complex. They are then relayed to the TOB complex, which mediates their insertion
      into the outer membrane. We studied the structure-function relationships of the
      core component of the TOB complex, Tob55. Tob55 precursors with deletions in the
      N-terminal domain were not affected in their targeting to and insertion into the
      mitochondrial outer membrane. Replacement of wild-type Tob55 by these deletion
      variants resulted in reduced growth of cells, and mitochondria isolated from such
      cells were impaired in their capacity to import beta-barrel precursors. The
      purified N-terminal domain was able to bind beta-barrel precursors in a specific
      manner. Collectively, these results demonstrate that the N-terminal domain of
      Tob55 recognizes precursors of beta-barrel proteins. This recognition may
      contribute to the coupling of the translocation of beta-barrel precursors across
      the TOM complex to their interaction with the TOB complex.

PMID- 17190790
TI  - Dissociation of estrogen receptor expression and in vivo stem cell activity in
      the mammary gland.
AB  - The role of estrogen in promoting mammary stem cell proliferation remains
      controversial. It is unclear if estrogen receptor (ER)-expressing cells have
      stem/progenitor activity themselves or if they act in a paracrine fashion to
      stimulate stem cell proliferation. We have used flow cytometry to prospectively
      isolate mouse mammary ER-expressing epithelial cells and shown, using analysis of
      gene expression patterns and cell type-specific markers, that they form a
      distinct luminal epithelial cell subpopulation that expresses not only the ER but
      also the progesterone and prolactin receptors. Furthermore, we have used an in
      vivo functional transplantation assay to directly demonstrate that the ER
      expressing luminal epithelial subpopulation contains little in vivo stem cell
      activity. Rather, the mammary stem cell activity is found within the basal
      mammary epithelial cell population. Therefore, ER-expressing cells of the mammary
      epithelium are distinct from the mammary stem cell population, and the effects of
      estrogen on mammary stem cells are likely to be mediated indirectly. These
      results are important for our understanding of cellular responses to hormonal
      stimulation in the normal breast and in breast cancer.

PMID- 17190792
TI  - Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA
      leading to localized inhibition of contractility.
AB  - Rho GTPases participate in various cellular processes, including normal and tumor
      cell migration. It has been reported that RhoA is targeted for degradation at the
      leading edge of migrating cells by the E3 ubiquitin ligase Smurf1, and that this
      is required for the formation of protrusions. We report that Smurf1-dependent
      RhoA degradation in tumor cells results in the down-regulation of Rho kinase
      (ROCK) activity and myosin light chain 2 (MLC2) phosphorylation at the cell
      periphery. The localized inhibition of contractile forces is necessary for the
      formation of lamellipodia and for tumor cell motility in 2D tissue culture
      assays. In 3D invasion assays, and in in vivo tumor cell migration, the
      inhibition of Smurf1 induces a mesenchymal-amoeboid-like transition that is
      associated with a more invasive phenotype. Our results suggest that Smurf1 is a
      pivotal regulator of tumor cell movement through its regulation of RhoA
      signaling.

PMID- 17190791
TI  - Regulation of activity and localization of the WNK1 protein kinase by
      hyperosmotic stress.
AB  - Mutations within the WNK1 (with-no-K[Lys] kinase-1) gene cause Gordon's
      hypertension syndrome. Little is known about how WNK1 is regulated. We
      demonstrate that WNK1 is rapidly activated and phosphorylated at multiple
      residues after exposure of cells to hyperosmotic conditions and that activation
      is mediated by the phosphorylation of its T-loop Ser382 residue, possibly
      triggered by a transautophosphorylation reaction. Activation of WNK1 coincides
      with the phosphorylation and activation of two WNK1 substrates, namely, the
      protein kinases STE20/SPS1-related proline alanine-rich kinase (SPAK) and
      oxidative stress response kinase-1 (OSR1). Small interfering RNA depletion of
      WNK1 impairs SPAK/OSR1 activity and phosphorylation of residues targeted by WNK1.
      Hyperosmotic stress induces rapid redistribution of WNK1 from the cytosol to
      vesicular structures that may comprise trans-Golgi network (TGN)/recycling
      endosomes, as they display rapid movement, colocalize with clathrin, adaptor
      protein complex 1 (AP-1), and TGN46, but not the AP-2 plasma membrane-coated pit
      marker nor the endosomal markers EEA1, Hrs, and LAMP1. Mutational analysis
      suggests that the WNK1 C-terminal noncatalytic domain mediates vesicle
      localization. Our observations shed light on the mechanism by which WNK1 is
      regulated by hyperosmotic stress.

PMID- 17190793
TI  - Synaptotagmin-12, a synaptic vesicle phosphoprotein that modulates spontaneous
      neurotransmitter release.
AB  - Central synapses exhibit spontaneous neurotransmitter release that is selectively
      regulated by cAMP-dependent protein kinase A (PKA). We now show that synaptic
      vesicles contain synaptotagmin-12, a synaptotagmin isoform that differs from
      classical synaptotagmins in that it does not bind Ca(2+). In synaptic vesicles,
      synaptotagmin-12 forms a complex with synaptotagmin-1 that prevents synaptotagmin
      1 from interacting with SNARE complexes. We demonstrate that synaptotagmin-12 is
      phosphorylated by cAMP-dependent PKA on serine(97), and show that expression of
      synaptotagmin-12 in neurons increases spontaneous neurotransmitter release by
      approximately threefold, but has no effect on evoked release. Replacing
      serine(97) by alanine abolishes synaptotagmin-12 phosphorylation and blocks its
      effect on spontaneous release. Our data suggest that spontaneous synaptic-vesicle
      exocytosis is selectively modulated by a Ca(2+)-independent synaptotagmin
      isoform, synaptotagmin-12, which is controlled by cAMP-dependent phosphorylation.

PMID- 17190794
TI  - Prophase I arrest and progression to metaphase I in mouse oocytes are controlled
      by Emi1-dependent regulation of APC(Cdh1).
AB  - Mammalian oocytes are arrested in prophase of the first meiotic division.
      Progression into the first meiotic division is driven by an increase in the
      activity of maturation-promoting factor (MPF). In mouse oocytes, we find that
      early mitotic inhibitor 1 (Emi1), an inhibitor of the anaphase-promoting complex
      (APC) that is responsible for cyclin B destruction and inactivation of MPF, is
      present at prophase I and undergoes Skp1-Cul1-F-box/betaTrCP-mediated destruction
      immediately after germinal vesicle breakdown (GVBD). Exogenous Emi1 or the
      inhibition of Emi1 destruction in prophase-arrested oocytes leads to a
      stabilization of cyclin B1-GFP that is sufficient to trigger GVBD. In contrast,
      the depletion of Emi1 using morpholino oligonucleotides increases cyclin B1-GFP
      destruction, resulting in an attenuation of MPF activation and a delay of entry
      into the first meiotic division. Finally, we show that Emi1-dependent effects on
      meiosis I require the presence of Cdh1. These observations reveal a novel
      mechanism for the control of entry into the first meiotic division: an Emi1
      dependent inhibition of APC(Cdh1).

PMID- 17190795
TI  - The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten
      regulates focal adhesion localization and growth suppression activity of DLC-1.
AB  - The tensin family member cten (C-terminal tensin like) is an Src homology 2 (SH2)
      and phosphotyrosine binding domain-containing focal adhesion molecule that may
      function as a tumor suppressor. However, the mechanism has not been well
      established. We report that cten binds to another tumor suppressor, deleted in
      liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the
      interaction. Unexpectedly, the interaction between DLC-1 and the cten SH2 domain
      is independent of tyrosine phosphorylation of DLC-1. By site-directed
      mutagenesis, we have identified several amino acid residues on cten and DLC-1
      that are essential for this interaction. Mutations on DLC-1 perturb the
      interaction with cten and disrupt the focal adhesion localization of DLC-1.
      Furthermore, these DLC-1 mutants have lost their tumor suppression activities.
      When these DLC-1 mutants were fused to a focal adhesion targeting sequence, their
      tumor suppression activities were significantly restored. These results provide a
      novel mechanism whereby the SH2 domain of cten-mediated focal adhesion
      localization of DLC-1 plays an essential role in its tumor suppression activity.

PMID- 17190796
TI  - Oxygen isotopic composition of carbon dioxide in the middle atmosphere.
AB  - The isotopic composition of long-lived trace molecules provides a window into
      atmospheric transport and chemistry. Carbon dioxide is a particularly powerful
      tracer, because its abundance remains >100 parts per million by volume (ppmv) in
      the mesosphere. Here, we successfully reproduce the isotopic composition of CO(2)
      in the middle atmosphere, which has not been previously reported. The mass
      independent fractionation of oxygen in CO(2) can be satisfactorily explained by
      the exchange reaction with O((1)D). In the stratosphere, the major source of
      O((1)D) is O(3) photolysis. Higher in the mesosphere, we discover that the
      photolysis of (16)O(17)O and (16)O(18)O by solar Lyman-alpha radiation yields
      O((1)D) 10-100 times more enriched in (17)O and (18)O than that from ozone
      photodissociation at lower altitudes. This latter source of heavy O((1)D) has not
      been considered in atmospheric simulations, yet it may potentially affect the
      "anomalous" oxygen signature in tropospheric CO(2) that should reflect the gross
      carbon fluxes between the atmosphere and terrestrial biosphere. Additional
      laboratory and atmospheric measurements are therefore proposed to test our model
      and validate the use of CO(2) isotopic fractionation as a tracer of atmospheric
      chemical and dynamical processes.

PMID- 17190797
TI  - Long-lasting and transmission-blocking activity of antibodies to Plasmodium
      falciparum elicited in mice by protein conjugates of Pfs25.
AB  - Malaria is a leading cause of morbidity and mortality, estimated to cause >1
      million childhood deaths annually. Plasmodium falciparum causes the most severe
      form of the disease. There is as yet no licensed vaccine for this disease,
      despite over a half century of research. In this study, we investigated a
      transmission-blocking vaccine candidate, the ookinete surface protein Pfs25.
      Antibodies against Pfs25, drawn in during a bite, can block parasite development
      in the mosquito midgut, preventing transmission to other individuals. Pfs25 is a
      low-molecular-weight protein, by itself not immunogenic. To increase its
      immunogenicity, we investigated several methods of conjugating Pfs25 to itself
      and to other proteins: recombinant Pseudomonas aeruginosa exotoxin A, and
      ovalbumin, using amide, hydrazone, or thioether linkages. All conjugates were
      immunogenic and induced booster responses in mice. The scheme to form amide bonds
      between proteins by using adipic acid dihydrizide as a linker produced the most
      immunogenic conjugates. Adsorption of the conjugates onto aluminum hydroxide
      further increased the antibody response. Remarkably, the antibody levels 3 or 7
      months after the last injection were significantly higher than those 1 wk after
      that injection. The observed transmission-blocking activity of immune sera
      correlated with antibody levels measured by ELISA.

PMID- 17190798
TI  - Short wavelength topography on the inner-core boundary.
AB  - Constraining the topography of the inner-core boundary is important for studies
      of core-mantle coupling and the generation of the geodynamo. We present evidence
      for significant temporal variability in the amplitude of the inner core reflected
      phase PKiKP for an exceptionally high-quality earthquake doublet, observed
      postcritically at the short-period Yellowknife seismic array (YK), which occurred
      in the South Sandwich Islands within a 10-year interval (1993/2003). This
      observation, complemented by data from several other doublets, indicates the
      presence of topography at the inner-core boundary, with a horizontal wavelength
      on the order of 10 km. Such topography could be sustained by small-scale
      convection at the top of the inner core and is compatible with a rate of super
      rotation of the inner core of approximately 0.1-0.15 degrees per year. In the
      absence of inner-core rotation, decadal scale temporal changes in the inner-core
      boundary topography would provide an upper bound on the viscosity at the top of
      the inner core.

PMID- 17190799
TI  - Inhibitory complex of the transmembrane ammonia channel, AmtB, and the cytosolic
      regulatory protein, GlnK, at 1.96 A.
AB  - Ammonia conductance is highly regulated. A P(II) signal transduction protein,
      GlnK, is the final regulator of transmembrane ammonia conductance by the ammonia
      channel AmtB in Escherichia coli. The complex formed between AmtB and inhibitory
      GlnK at 1.96-A resolution shows that the trimeric channel is blocked directly by
      GlnK and how, in response to intracellular nitrogen status, the ability of GlnK
      to block the channel is regulated by uridylylation/deuridylylation at Y51. ATP
      and Mg(2+) augment the interaction of GlnK. The hydrolyzed product, adenosine 5'
      diphosphate orients the surface of GlnK for AmtB blockade. 2-Oxoglutarate
      diminishes AmtB/GlnK association, and sites for 2-oxoglutarate are evaluated.

PMID- 17190800
TI  - Coupled transport at the nanoscale: the unreasonable effectiveness of equilibrium
      theory.

PMID- 17190801
TI  - Oxidized messenger RNA induces translation errors.
AB  - To investigate the effect of RNA oxidation on normal cellular functions, we
      studied the translation of nonoxidized and oxidized luciferase mRNA in both
      rabbit reticulocyte lysate and human HEK293 cells. When HEK293 cells transfected
      with nonoxidized mRNA encoding the firefly luciferase protein were cultured in
      the presence of paraquat, there was a paraquat concentration-dependent increase
      in the formation of luciferase short polypeptides (SPs) concomitant with an
      increase in 8-oxoguanosine. Short polypeptides were also formed when the mRNA was
      oxidized in vitro by the Fe-ascorbate-H(2)O(2) metal-catalyzed oxidation system
      before its transfection into cells. Translation of the in vitro oxidized mRNA in
      rabbit reticulocyte lysate also led to formation of SPs. The SPs formed by either
      procedure contained the N-terminal and the C-terminal portions of the tagged
      luciferase. In addition, the oxidized mRNA was able to associate with ribosomes
      to form polysomes similar to those formed with nonoxidized mRNA preparations,
      indicating that the oxidized mRNAs are mostly intact; however, their translation
      fidelity was significantly reduced. Nevertheless, our results indicate that the
      SPs were derived from both premature termination of the translation process of
      the oxidized mRNA and the proteolytic degradation of the modified full-length
      luciferase resulting from translation errors induced by oxidized mRNA. In light
      of these findings, the physiological consequences of mRNA oxidation are
      discussed.

PMID- 17190802
TI  - Eukaryotic operon-like transcription of functionally related genes in Drosophila.
AB  - Complex biological processes require coordinated function of many genes. One
      evolutionary solution to the problem of coordinately expressing functionally
      related genes in bacteria and nematodes is organization of genes in operons.
      Surprisingly, eukaryotic operons are considered rare outside the nematode
      lineage. In Drosophila melanogaster, we found lounge lizard (llz), which encodes
      a degenerin/ENaC cation channel, cotranscribed with CheB42a, a nonhomologous gene
      of unknown function residing <100 bp upstream. These two genes were transcribed
      from a single promoter as one primary transcript and were processed
      posttranscriptionally to generate individual mRNAs. The mechanism did not involve
      alternative splicing, and it differed from the trans splicing used in nematode
      operons. Both genes were expressed in the same tissues, and previous work
      suggested that both may be involved in courtship behavior. A bioinformatic
      approach identified numerous additional loci as potential Drosophila operons.
      These data reveal eukaryotic operon-like transcription of functionally related
      genes in Drosophila. The results also suggest that operon-based transcription may
      be more common in eukaryotes than previously appreciated.

PMID- 17190803
TI  - The tetraspanin CD9 mediates lateral association of MHC class II molecules on the
      dendritic cell surface.
AB  - We have found that MHC class II (MHC II) molecules exhibit a distinctive
      organization on the dendritic cell (DC) plasma membrane. Both in DC lysates and
      on the surface of living cells, I-A and I-E molecules engaged in lateral
      interactions not observed on other antigen-presenting cells such as B blasts.
      Because DCs and B blasts express MHC II at comparable surface densities, the
      interaction was not due to simple mass action. Instead, it reflected the
      selective expression of the tetraspanin CD9 at the DC surface. I-A and I-E
      molecules coprecipitated with each other and with CD9. The association of
      heterologous MHC II molecules was abrogated in DCs from CD9(-/-) mice.
      Conversely, expression of exogenous CD9 in B cells induced MHC II interactions.
      CD9 is thus necessary for the association of heterologous MHC II, a
      specialization that would facilitate the formation of MHC II multimers expected
      to enhance T cell receptor stimulation by DCs.

PMID- 17190804
TI  - Penetrating arterioles are a bottleneck in the perfusion of neocortex.
AB  - Penetrating arterioles bridge the mesh of communicating arterioles on the surface
      of cortex with the subsurface microvascular bed that feeds the underlying neural
      tissue. We tested the conjecture that penetrating arterioles, which are
      positioned to regulate the delivery of blood, are loci of severe ischemia in the
      event of occlusion. Focal photothrombosis was used to occlude single penetrating
      arterioles in rat parietal cortex, and the resultant changes in flow of red blood
      cells were measured with two-photon laser-scanning microscopy in individual
      subsurface microvessels that surround the occlusion. We observed that the average
      flow of red blood cells nearly stalls adjacent to the occlusion and remains
      within 30% of its baseline value in vessels as far as 10 branch points downstream
      from the occlusion. Preservation of average flow emerges 350 mum away; this
      length scale is consistent with the spatial distribution of penetrating
      arterioles. We conclude that penetrating arterioles are a bottleneck in the
      supply of blood to neocortex, at least to superficial layers.

PMID- 17190806
TI  - A singular enzymatic megacomplex from Bacillus subtilis.
AB  - Nonribosomal peptide synthetases (NRPS), polyketide synthases (PKS), and hybrid
      NRPS/PKS are of particular interest, because they produce numerous therapeutic
      agents, have great potential for engineering novel compounds, and are the largest
      enzymes known. The predicted masses of known enzymatic assembly lines can reach
      almost 5 megadaltons, dwarfing even the ribosome (approximately 2.6 megadaltons).
      Despite their uniqueness and importance, little is known about the organization
      of these enzymes within the native producer cells. Here we report that an 80-kb
      gene cluster, which occupies approximately 2% of the Bacillus subtilis genome,
      encodes the subunits of approximately 2.5 megadalton active hybrid NRPS/PKS. Many
      copies of the NRPS/PKS assemble into a single organelle-like membrane-associated
      complex of tens to hundreds of megadaltons. Such an enzymatic megacomplex is
      unprecedented in bacterial subcellular organization and has important
      implications for engineering novel NRPS/PKSs.

PMID- 17190805
TI  - Conserved markers of fetal pancreatic epithelium permit prospective isolation of
      islet progenitor cells by FACS.
AB  - Prospective isolation and characterization of progenitor cells is a paradigmatic
      strategy for studies of organ development. However, extraction of viable cells,
      fractionation of lineages, and in vitro analysis of progenitors from the fetal
      pancreas in experimental organisms like mice has proved challenging and has not
      yet been reported for human fetal pancreas. Here, we report isolation of
      pancreatic islet progenitor cells from fetal mice by FACS. Monoclonal antibodies
      that recognize cell-surface proteins on candidate stem cells in brain, skin, and
      other organs enabled separation of major pancreatic cell lineages and isolation
      of native pancreatic cells expressing neurogenin 3, an established marker of
      islet progenitors. New in vitro cell culture methods permitted isolated mouse
      islet progenitors to develop into hormone-expressing endocrine cells. Insulin
      producing cells derived in vitro required or expressed factors that regulate
      fetal beta cell differentiation; thus, the genetic programs normally controlling
      in vivo mouse islet development are similarly required in our system. Moreover,
      antibodies that recognize conserved orthologous cell-surface epitopes in human
      fetal pancreas allowed FACS-based enrichment of candidate islet progenitor cells
      expressing neurogenin 3. Our studies reveal previously undescribed strategies for
      prospective purification and analysis of pancreatic endocrine progenitor cells
      that should accelerate studies of islet development and replacement.

PMID- 17190807
TI  - Independent control of grafting density and conformation of single-stranded DNA
      brushes.
AB  - We describe self-assembly of ssDNA brushes that exploits the intrinsic affinity
      of adenine nucleotides (dA) for gold surfaces. The grafting density and
      conformation of these brushes is deterministically controlled by the length of
      the anchoring dA sequences, even in the presence of thymine nucleotides (dT). We
      produce and characterize brushes of model block-oligonucleotides, d(T(m)-A(n)),
      with systematically varied lengths m and n of the thymine and adenine blocks
      [denoted d(T(m)) and d(A(n)), respectively]. The hairpin conformation, dominant
      for self-complementary d(T(m)-A(n)) oligos in solution, is disrupted by the high
      preferential affinity of dA for gold surfaces. As a result, the d(T(m)-A(n))
      oligos adsorb as a brush of d(T) strands immobilized via the d(A) blocks.
      Quantitative analysis by FTIR spectroscopy and x-ray photoelectron spectroscopy
      (XPS) reveals a unique feature of DNA immobilization via d(A) blocks: The surface
      density of dA nucleotides is close to saturation and is nearly independent of
      d(A) block length. Accordingly, the lateral spacing (grafting density) of the
      d(T) blocks is determined by the length of the d(A) blocks. The d(T) blocks
      extend away from the surface in a brush-like conformation at a lateral spacing 2
      3 times larger (a grafting density 5-10 times lower) than in analogous films
      immobilized via standard thiol linkers. This combination of brush-like
      conformation and low saturation grafting density is expected to increase the
      efficiency of DNA hybridization at surfaces. Therefore, immobilization via d(A)
      blocks offers a method of producing DNA brushes with controlled properties for
      applications in biotechnology and nanotechnology.

PMID- 17190808
TI  - Multiple-motor based transport and its regulation by Tau.
AB  - Motor-based intracellular transport and its regulation are crucial to the
      functioning of a cell. Disruption of transport is linked to Alzheimer's and other
      neurodegenerative diseases. However, many fundamental aspects of transport are
      poorly understood. An important issue is how cells achieve and regulate efficient
      long-distance transport. Mounting evidence suggests that many in vivo cargoes are
      transported along microtubules by more than one motor, but we do not know how
      multiple motors work together or can be regulated. Here we first show that
      multiple kinesin motors, working in conjunction, can achieve very long distance
      transport and apply significantly larger forces without the need of additional
      factors. We then demonstrate in vitro that the important microtubule-associated
      protein, tau, regulates the number of engaged kinesin motors per cargo via its
      local concentration on microtubules. This function of tau provides a previously
      unappreciated mechanism to regulate transport. By reducing motor reattachment
      rates, tau affects cargo travel distance, motive force, and cargo dispersal. We
      also show that different isoforms of tau, at concentrations similar to those in
      cells, have dramatically different potency. These results provide a well defined
      mechanism for how altered tau isoform levels could impair transport and thereby
      lead to neurodegeneration without the need of any other pathway.

PMID- 17190809
TI  - A unique configuration of genome-wide DNA methylation patterns in the testis.
AB  - In the mammalian lifecycle, the two periods of genome-wide epigenetic
      reprogramming are in the early embryo, when somatic patterns are set, and during
      germ cell development. Although some differences between the reprogrammed states
      of somatic and germ cells have been reported, overall patterns of genomic
      methylation are considered to be similar. Using restriction landmark genomic
      scanning to examine approximately 2,600 loci distributed randomly throughout the
      genome, we find that the methylation status of testicular DNA is highly distinct,
      displaying eightfold the number of hypomethylated loci relative to somatic
      tissues. Identification and analysis of >300 loci show that these regions are
      generally located within nonrepetitive sequences that are away from CpG islands
      and 5' regions of genes. We show that a contributing factor for these differences
      is that the methylation state of non-CpG-island DNA is correlated with the
      regional level of GC content within chromosomes and that this relationship is
      inverted between the testis and somatic tissues. We also show that in Dnmt3L
      deficient mice, which exhibit infertility associated with abnormal chromosomal
      structures in germ cells, this unique testicular DNA methylation pattern is not
      established. These special properties of testicular DNA point to a broad,
      distinct epigenetic state that may be involved in maintaining a unique
      chromosomal structure in male germ cells.

PMID- 17190810
TI  - Activity-dependent neurotransmitter-receptor matching at the neuromuscular
      junction.
AB  - Signaling in the nervous system requires matching of neurotransmitter receptors
      with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction
      is the best studied cholinergic synapse, but the mechanisms by which
      acetylcholine is matched with acetylcholine receptors are not fully understood.
      Because alterations in neuronal calcium spike activity alter transmitter
      specification in embryonic spinal neurons, we hypothesized that receptor
      expression in postsynaptic cells follows changes in transmitter expression to
      achieve this specific match. We find that embryonic vertebrate striated muscle
      cells normally express receptors for glutamate, GABA, and glycine as well as for
      acetylcholine. As maturation progresses, acetylcholine receptor expression
      prevails. Receptor selection is altered when early neuronal calcium-dependent
      activity is perturbed, and remaining receptor populations parallel changes in
      transmitter phenotype. In these cases, glutamatergic, GABAergic, and glycinergic
      synaptic currents are recorded from muscle cells, demonstrating that activity
      regulates matching of transmitters and their receptors in the assembly of
      functional synapses.

PMID- 17190811
TI  - Monomer adds to preformed structured oligomers of Abeta-peptides by a two-stage
      dock-lock mechanism.
AB  - Nonfibrillar soluble oligomers, which are intermediates in the transition from
      monomers to amyloid fibrils, may be the toxic species in Alzheimer's disease. To
      monitor the early events that direct assembly of amyloidogenic peptides we probe
      the dynamics of formation of (Abeta(16-22))(n) by adding a monomer to a preformed
      (Abeta(16-22))(n-1) (n = 4-6) oligomer in which the peptides are arranged in an
      antiparallel beta-sheet conformation. All atom molecular dynamics simulations in
      water and multiple long trajectories, for a cumulative time of 6.9 mus, show that
      the oligomer grows by a two-stage dock-lock mechanism. The largest conformational
      change in the added disordered monomer occurs during the rapid ( approximately 50
      ns) first dock stage in which the beta-strand content of the monomer increases
      substantially from a low initial value. In the second slow-lock phase, the
      monomer rearranges to form in register antiparallel structures. Surprisingly, the
      mobile structured oligomers undergo large conformational changes in order to
      accommodate the added monomer. The time needed to incorporate the monomer into
      the fluid-like oligomer grows even when n = 6, which suggests that the critical
      nucleus size must exceed six. Stable antiparallel structure formation exceeds
      hundreds of nanoseconds even though frequent interpeptide collisions occur at
      elevated monomer concentrations used in the simulations. The dock-lock mechanism
      should be a generic mechanism for growth of oligomers of amyloidogenic peptides.

PMID- 17190812
TI  - Genetic regulation of patterned tubular branching in Drosophila.
AB  - A common theme in organogenesis is the branching of epithelial tubes, for example
      in the lung, liver, or kidney. The later morphogenesis of these branched
      epithelia dictates the final form and function of the mature tissue. Epithelial
      branching requires the specification of branch cells, the eversion process
      itself, and, frequently, patterned morphogenesis to produce branches of specific
      shape and orientation. Using the branching of renal tubule primordia from the
      hindgut in Drosophila, we show that these aspects are coordinately regulated.
      Cell specification depends on Wnt signaling along the tubular gut and results in
      the spatially restricted coexpression of two transcription factors, Kruppel and
      Cut, in the hindgut, whose activity drives cells toward renal tubule fate.
      Significantly, these transcription factors also confer the competence to respond
      to a second signal; TGF-beta induces branching to form the four renal tubule
      buds. Differential activation of the TGF-beta pathway also patterns the tubules,
      resulting in the asymmetry in size and positioning that is characteristic of the
      two tubule pairs. High levels of TGF-beta promote the expression of Dorsocross1-3
      and anterior tubule growth, whereas low levels allow the expression of the
      transcriptional repressor, Brinker, and thus promote posterior tubule identity.
      We show that patterning of the tubule primordium into two distinct pairs is
      critical for the eversion of tubule branches, as well as for their asymmetric
      morphogenesis.

PMID- 17190813
TI  - N-formylation of lysine in histone proteins as a secondary modification arising
      from oxidative DNA damage.
AB  - The posttranslational modification of histone and other chromatin proteins has a
      well recognized but poorly defined role in the physiology of gene expression.
      With implications for interfering with these epigenetic mechanisms, we now report
      the existence of a relatively abundant secondary modification of chromatin
      proteins, the N(6)-formylation of lysine that appears to be uniquely associated
      with histone and other nuclear proteins. Using both radiolabeling and sensitive
      bioanalytical methods, we demonstrate that the formyl moiety of 3'
      formylphosphate residues arising from 5'-oxidation of deoxyribose in DNA, caused
      by the enediyne neocarzinostatin, for example, acylate the N(6)-amino groups of
      lysine side chains. A liquid chromatography (LC)-tandem mass spectrometry (MS)
      method was developed to quantify the resulting N(6)-formyl-lysine residues, which
      were observed to be present in unperturbed cells and all sources of histone
      proteins to the extent of 0.04-0.1% of all lysines in acid-soluble chromatin
      proteins including histones. Cells treated with neocarzinostatin showed a clear
      dose-response relationship for the formation of N(6)-formyl-lysine, with this
      nucleosome linker-selective DNA-cleaving agent causing selective N(6)-formylation
      of the linker histone H1. The N(6)-formyl-lysine residue appears to represent an
      endogenous histone secondary modification, one that bears chemical similarity to
      lysine N(6)-acetylation recognized as an important determinant of gene expression
      in mammalian cells. The N(6)-formyl modification of lysine may interfere with the
      signaling functions of lysine acetylation and methylation and thus contribute to
      the pathophysiology of oxidative and nitrosative stress.

PMID- 17190814
TI  - Regulation of innate antiviral defenses through a shared repressor domain in RIG
      I and LGP2.
AB  - RIG-I is an RNA helicase containing caspase activation and recruitment domains
      (CARDs). RNA binding and signaling by RIG-I are implicated in pathogen
      recognition and triggering of IFN-alpha/beta immune defenses that impact cell
      permissiveness for hepatitis C virus (HCV). Here we evaluated the processes that
      control RIG-I signaling. RNA binding studies and analysis of cells lacking RIG-I,
      or the related MDA5 protein, demonstrated that RIG-I, but not MDA5, efficiently
      binds to secondary structured HCV RNA to confer induction of IFN-beta expression.
      We also found that LGP2, a helicase related to RIG-I and MDA5 but lacking CARDs
      and functioning as a negative regulator of host defense, binds HCV RNA. In
      resting cells, RIG-I is maintained as a monomer in an autoinhibited state, but
      during virus infection and RNA binding it undergoes a conformation shift that
      promotes self-association and CARD interactions with the IPS-1 adaptor protein to
      signal IFN regulatory factor 3- and NF-kappaB-responsive genes. This reaction is
      governed by an internal repressor domain (RD) that controls RIG-I multimerization
      and IPS-1 interaction. Deletion of the RIG-I RD resulted in constitutive
      signaling to the IFN-beta promoter, whereas RD expression alone prevented
      signaling and increased cellular permissiveness to HCV. We identified an
      analogous RD within LGP2 that interacts in trans with RIG-I to ablate self
      association and signaling. Thus, RIG-I is a cytoplasmic sensor of HCV and is
      governed by RD interactions that are shared with LGP2 as an on/off switch
      controlling innate defenses. Modulation of RIG-I/LGP2 interaction dynamics may
      have therapeutic implications for immune regulation.

PMID- 17190815
TI  - Nuclear IKK activity leads to dysregulated notch-dependent gene expression in
      colorectal cancer.
AB  - Nuclear functions for IkappaB kinase (IKK), including phosphorylation of histone
      H3 and nuclear corepressors, have been recently described. Here, we show that IKK
      is activated in colorectal tumors concomitant with the presence of phosphorylated
      SMRT (silencing mediator of retinoic acid and thyroid hormone receptor)
      corepressor that is aberrantly localized in the cytoplasm. In these tumors,
      IKKalpha associates to the chromatin of specific Notch targets, leading to the
      release of SMRT. Abrogation of IKK activity by BAY11-7082 or by expressing
      dominant negative IKKalpha restores the association of SMRT with Notch target
      genes, resulting in specific gene repression. Finally, BAY11-7082 significantly
      reduces tumor size in colorectal cancer xenografts (CRC-Xs) implanted in nude
      mice.

PMID- 17190816
TI  - Structure and quantum chemical characterization of chloroperoxidase compound 0, a
      common reaction intermediate of diverse heme enzymes.
AB  - We have determined the crystal structure of the chloroperoxidase (CPO)
      hydroperoxo reaction intermediate (CPO compound 0) at 1.75-A resolution. The
      intermediate was generated through controlled photoreduction of the CPO oxygen
      complex during x-ray data collection, which was monitored by recording of the
      crystal absorption spectra. Initially, the peroxo-anion species was formed and
      then protonated to yield compound 0. Quantum chemical calculations indicate that
      the peroxo-anion species is not stable and collapses instantaneously to compound
      0. Compound 0 is present in the ferric low-spin doublet ground state and is
      characterized by a long O O bond length of 1.5 A and a Fe O bond distance of 1.8
      A, which is also observed in the crystal structure.

PMID- 17190817
TI  - Antitumor NK activation induced by the Toll-like receptor 3-TICAM-1 (TRIF)
      pathway in myeloid dendritic cells.
AB  - Myeloid dendritic cells (mDCs) recognize and respond to polyI:C, an analog of
      dsRNA, by endosomal Toll-like receptor (TLR) 3 and cytoplasmic receptors. Natural
      killer (NK) cells are activated in vivo by the administration of polyI:C to mice
      and in vivo are reciprocally activated by mDCs, although the molecular mechanisms
      are as yet undetermined. Here, we show that the TLR adaptor TICAM-1 (TRIF)
      participates in mDC-derived antitumor NK activation. In a syngeneic mouse tumor
      implant model (C57BL/6 vs. B16 melanoma with low H-2 expresser), i.p.
      administration of polyI:C led to the retardation of tumor growth, an effect
      relied on by NK activation. This NK-dependent tumor regression did not occur in
      TICAM-1(-/-) or IFNAR(-/-) mice, whereas a normal NK antitumor response was
      induced in PKR(-/-), MyD88(-/-), IFN-beta(-/-), and wild-type mice. IFNAR was a
      prerequisite for the induction of IFN-alpha/beta and TLR3. The lack of TICAM-1
      did not affect IFN production but resulted in unresponsiveness to IL-12
      production, mDC maturation, and polyI:C-mediated NK-antitumor activity. This NK
      activation required NK-mDC contact but not IL-12 function in in vivo transwell
      analysis. Implanted tumor growth in IFNAR(-/-) mice was retarded by adoptively
      transferring polyI:C-treated TICACM-1-positive mDCs but not TICAM-1(-/-) mDCs.
      Thus, TICAM-1 in mDCs critically facilitated mDC-NK contact and activation of
      antitumor NK, resulting in the regression of low MHC-expressing tumors.

PMID- 17190818
TI  - Resolution limit in community detection.
AB  - Detecting community structure is fundamental for uncovering the links between
      structure and function in complex networks and for practical applications in many
      disciplines such as biology and sociology. A popular method now widely used
      relies on the optimization of a quantity called modularity, which is a quality
      index for a partition of a network into communities. We find that modularity
      optimization may fail to identify modules smaller than a scale which depends on
      the total size of the network and on the degree of interconnectedness of the
      modules, even in cases where modules are unambiguously defined. This finding is
      confirmed through several examples, both in artificial and in real social,
      biological, and technological networks, where we show that modularity
      optimization indeed does not resolve a large number of modules. A check of the
      modules obtained through modularity optimization is thus necessary, and we
      provide here key elements for the assessment of the reliability of this community
      detection method.

PMID- 17190819
TI  - Risk assessment for invasive species produces net bioeconomic benefits.
AB  - International commerce in live organisms presents a policy challenge for trade
      globalization; sales of live organisms create wealth, but some nonindigenous
      species cause harm. To reduce damage, some countries have implemented species
      screening to limit the introduction of damaging species. Adoption of new risk
      assessment (RA) technologies has been slowed, however, by concerns that RA
      accuracy remains insufficient to produce positive net economic benefits. This
      concern arises because only a small proportion of all introduced species escape,
      spread, and cause harm (i.e., become invasive), so a RA will exclude many
      noninvasive species (which provide a net economic benefit) for every invasive
      species correctly identified. Here, we develop a simple cost:benefit bioeconomic
      framework to quantify the net benefits from applying species prescreening.
      Because invasive species are rarely eradicated, and their damages must therefore
      be borne for long periods, we have projected the value of RA over a suitable
      range of policy time horizons (10-500 years). We apply the model to the
      Australian plant quarantine program and show that this RA program produces
      positive net economic benefits over the range of reasonable assumptions. Because
      we use low estimates of the financial damage caused by invasive species and high
      estimates of the value of species in the ornamental trade, our results
      underestimate the net benefit of the Australian plant quarantine program. In
      addition, because plants have relatively low rates of invasion, applying
      screening protocols to animals would likely demonstrate even greater benefits.

PMID- 17190820
TI  - The Iranian petroleum crisis and United States national security.
AB  - The U.S. case against Iran is based on Iran's deceptions regarding nuclear
      weapons development. This case is buttressed by assertions that a state so
      petroleum-rich cannot need nuclear power to preserve exports, as Iran claims. The
      U.S. infers, therefore, that Iran's entire nuclear technology program must
      pertain to weapons development. However, some industry analysts project an Irani
      oil export decline [e.g., Clark JR (2005) Oil Gas J 103(18):34-39]. If such a
      decline is occurring, Iran's claim to need nuclear power could be genuine.
      Because Iran's government relies on monopoly proceeds from oil exports for most
      revenue, it could become politically vulnerable if exports decline. Here, we
      survey the political economy of Irani petroleum for evidence of this decline. We
      define Iran's export decline rate (edr) as its summed rates of depletion and
      domestic demand growth, which we find equals 10-12%. We estimate marginal cost
      per barrel for additions to Irani production capacity, from which we derive the
      "standstill" investment required to offset edr. We then compare the standstill
      investment to actual investment, which has been inadequate to offset edr. Even if
      a relatively optimistic schedule of future capacity addition is met, the ratio of
      2011 to 2006 exports will be only 0.40-0.52. A more probable scenario is that,
      absent some change in Irani policy, this ratio will be 0.33-0.46 with exports
      declining to zero by 2014-2015. Energy subsidies, hostility to foreign
      investment, and inefficiencies of its state-planned economy underlie Iran's
      problem, which has no relation to "peak oil."

PMID- 17190822
TI  - Ungulate herbivory: indirect effects cascade into the treetops.

PMID- 17190821
TI  - Toxin-antitoxin systems are ubiquitous and plasmid-encoded in vancomycin
      resistant enterococci.
AB  - Vancomycin-resistant enterococci (VRE) are common hospital pathogens that are
      resistant to most major classes of antibiotics. The incidence of VRE is
      increasing rapidly, to the point where over one-quarter of enterococcal
      infections in intensive care units are now resistant to vancomycin. The exact
      mechanism by which VRE maintains its plasmid-encoded resistance genes is ill
      defined, and novel targets for the treatment of VRE are lacking. In an effort to
      identify novel protein targets for the treatment of VRE infections, we probed the
      plasmids obtained from 75 VRE isolates for the presence of toxin-antitoxin (TA)
      gene systems. Remarkably, genes for one particular TA pair, the mazEF system
      (originally identified on the Escherichia coli chromosome), were present on
      plasmids from 75/75 (100%) of the isolates. Furthermore, mazEF was on the same
      plasmid as vanA in the vast majority of cases (>90%). Plasmid stability tests and
      RT-PCR raise the possibility that this plasmid-encoded mazEF is indeed functional
      in enterococci. Given this ubiquity of mazEF in VRE and the deleterious activity
      of the MazF toxin, disruption of mazEF with pharmacological agents is an
      attractive strategy for tailored antimicrobial therapy.

PMID- 17190823
TI  - Herbivore-initiated interaction cascades and their modulation by productivity in
      an African savanna.
AB  - Despite conceptual recognition that indirect effects initiated by large
      herbivores are likely to have profound impacts on ecological community structure
      and function, the existing literature on indirect effects focuses largely on the
      role of predators. As a result, we know neither the frequency and extent of
      herbivore-initiated indirect effects nor the mechanisms that regulate their
      strength. We examined the effects of ungulates on taxa (plants, arthropods, and
      an insectivorous lizard) representing several trophic levels, using a series of
      large, long-term, ungulate-exclusion plots that span a landscape-scale
      productivity gradient in an African savanna. At each of six sites, lizards,
      trees, and the numerically dominant order of arthropods (Coleoptera) were more
      abundant in the absence of ungulates. The effect of ungulates on arthropods was
      mediated by herbaceous vegetation cover. The effect on lizards was simultaneously
      mediated by both tree density (lizard microhabitat) and arthropod abundance
      (lizard food). The magnitudes of the experimental effects on all response
      variables (trees, arthropods, and lizards) were negatively correlated with two
      distinct measures of primary productivity. These results demonstrate strong
      cascading effects of ungulates, both trophic and nontrophic, and support the
      hypothesis that productivity regulates the strength of these effects. Hence, the
      strongest indirect effects (and thus, the greatest risks to ecosystem integrity
      after large mammals are extirpated) are likely to occur in low-productivity
      habitats.

PMID- 17190824
TI  - A neural basis for inference in perceptual ambiguity.
AB  - When looking at ambiguous visual stimuli, the observer experiences frequent
      spontaneous transitions between two competing percepts while physical stimulation
      remains unchanged. Despite recent advances in understanding the neural processes
      underlying such perceptual rivalry, a key question has remained unresolved: Does
      perceptual rivalry result merely from local bistability of neural activity
      patterns in sensory stimulus representations, or do higher-order areas play a
      causal role by shifting inference and, thus, initiating perceptual changes? We
      used functional MRI to measure brain activity while human observers reported
      successive spontaneous changes in perceived direction for an ambiguous apparent
      motion stimulus. In a control condition, the individual sequences of spontaneous
      perceptual switches during bistability were replayed by using a disambiguated
      version of the stimulus. Greater activations during spontaneous compared with
      stimulus-driven switches were observed in inferior frontal cortex bilaterally.
      Subsequent chronometric analyses of event-related signal time courses showed
      that, relative to activations in motion-sensitive extrastriate visual cortex,
      right inferior frontal cortex activation occurred earlier during spontaneous than
      during stimulus-driven perceptual changes. The temporal precedence of right
      inferior frontal activations suggests that this region participates in initiating
      spontaneous switches in perception during constant physical stimulation. Our
      findings can thus be seen as a signature of when and where the brain "makes up
      its mind" about competing perceptual interpretations of a given sensory input
      pattern.

PMID- 17190825
TI  - Parasitic inhibition of cell death facilitates symbiosis.
AB  - Symbiotic microorganisms have had a large impact on eukaryotic evolution, with
      effects ranging from parasitic to mutualistic. Mitochondria and chloroplasts are
      prime examples of symbiotic microorganisms that have become obligate for their
      hosts, allowing for a dramatic extension of suitable habitats for life. Out of
      the extraordinary diversity of bacterial endosymbionts in insects, most are
      facultative for their hosts, such as the ubiquitous Wolbachia, which manipulates
      host reproduction. Some endosymbionts, however, have become obligatory for host
      reproduction and/or survival. In the parasitoid wasp Asobara tabida the presence
      of Wolbachia is necessary for host oogenesis, but the mechanism involved is yet
      unknown. We show that Wolbachia influences programmed cell death processes (a
      host regulatory feature typically targeted by pathogens) in A. tabida, making its
      presence essential for the wasps' oocytes to mature. This suggests that parasite
      strategies, such as bacterial regulation of host apoptosis, can drive the
      evolution of host dependence, allowing for a swift transition from parasitism to
      mutualism.

PMID- 17190826
TI  - Par4 is required for platelet thrombus propagation but not fibrin generation in a
      mouse model of thrombosis.
AB  - Thrombin, a central mediator of hemostasis and thrombosis, converts fibrinogen to
      fibrin and is a potent platelet activator. Activated platelets provide a surface
      for assembly of the tenase and prothrombinase complexes required for thrombin
      generation. The role of thrombin-induced platelet activation in platelet
      accumulation and its interplay with fibrin deposition during thrombus assembly
      has not been fully defined. We studied these processes during laser-induced
      thrombus formation by using real-time digital fluorescence microscopy in mice
      lacking protease-activated receptor-4 (Par4), which is necessary for thrombin
      responsiveness in mouse platelets. Juxtamural platelet accumulation immediately
      after laser injury was not different in wild-type and Par4(-/-) mice. However,
      subsequent growth of platelet thrombi was markedly diminished in Par4(-/-) mice.
      At the time of maximal thrombus size in wild type, platelet accumulation was more
      than 10-fold higher in wild type than in Par4(-/-) mice. P-selectin expression, a
      marker of platelet activation, was reduced and delayed in Par4(-/-) thrombi. In
      contrast to platelet activation and accumulation, the rate and amount of fibrin
      deposition, predominantly intramural and juxtamural in this model, were
      indistinguishable in Par4(-/-) and wild-type mice. These results suggest that
      platelet activation by thrombin is necessary for normal propagation of a platelet
      thrombus at a distance from the injured vessel wall and hence for normal thrombus
      growth. However, platelet activation by thrombin is unnecessary for initial and
      limited accumulation of platelets at or near the vessel wall, and this limited
      accumulation of platelets and/or platelet-independent mechanism(s) of thrombin
      generation are sufficient for normal fibrin deposition in this model.

PMID- 17190827
TI  - Structural basis for intramembrane proteolysis by rhomboid serine proteases.
AB  - Intramembrane proteases catalyze peptide bond cleavage of integral membrane
      protein substrates. This activity is crucial for many biological and pathological
      processes. Rhomboids are evolutionarily widespread intramembrane serine
      proteases. Here, we present the 2.3-A-resolution crystal structure of a rhomboid
      from Escherichia coli. The enzyme has six transmembrane helices, five of which
      surround a short TM4, which starts deep within the membrane at the catalytic
      serine residue. Thus, the catalytic serine is in an externally exposed cavity,
      which provides a hydrophilic environment for proteolysis. Our results reveal a
      mechanism to enable water-dependent catalysis at the depth of the hydrophobic
      milieu of the membrane and suggest how substrates gain access to the sequestered
      rhomboid active site.

PMID- 17190828
TI  - Structure and orientation of the Mn4Ca cluster in plant photosystem II membranes
      studied by polarized range-extended x-ray absorption spectroscopy.
AB  - X-ray absorption spectroscopy has provided important insights into the structure
      and function of the Mn(4)Ca cluster in the oxygen-evolving complex of Photosystem
      II (PS II). The range of manganese extended x-ray absorption fine structure data
      collected from PS II until now has been, however, limited by the presence of iron
      in PS II. Using a crystal spectrometer with high energy resolution to detect
      solely the manganese Kalpha fluorescence, we are able to extend the extended x
      ray absorption fine structure range beyond the onset of the iron absorption edge.
      This results in improvement in resolution of the manganese-backscatterer
      distances in PS II from 0.14 to 0.09A(.) The high resolution data obtained from
      oriented spinach PS II membranes in the S(1) state show that there are three di
      mu-oxo-bridged manganese-manganese distances of approximately 2.7 and
      approximately 2.8A in a 2:1 ratio and that these three manganese-manganese
      vectors are aligned at an average orientation of approximately 60 degrees
      relative to the membrane normal. Furthermore, we are able to observe the
      separation of the Fourier peaks corresponding to the approximately 3.2A manganese
      manganese and the approximately 3.4A manganese-calcium interactions in oriented
      PS II samples and determine their orientation relative to the membrane normal.
      The average of the manganese-calcium vectors at approximately 3.4A is aligned
      along the membrane normal, while the approximately 3.2A manganese-manganese
      vector is oriented near the membrane plane. A comparison of this structural
      information with the proposed Mn(4)Ca cluster models based on spectroscopic and
      diffraction data provides input for refining and selecting among these models.

PMID- 17190829
TI  - Functional analysis of Arabidopsis thaliana RHM2/MUM4, a multidomain protein
      involved in UDP-D-glucose to UDP-L-rhamnose conversion.
AB  - UDP-L-rhamnose is required for the biosynthesis of cell wall rhamnogalacturonan
      I, rhamnogalacturonan-II, and natural compounds in plants. It has been suggested
      that the RHM2/MUM4 gene is involved in conversion of UDP-D-glucose to UDP-L
      rhamnose on the basis of its effect on rhamnogalacturonan-I-directed development
      in Arabidopsis thaliana. RHM2/MUM4-related genes, RHM1 and RHM3, can be found in
      the A. thaliana genome. Here we present direct evidence that all three RHM
      proteins have UDP-D-glucose 4,6-dehydratase, UDP-4-keto-6-deoxy-D-glucose 3,5
      epimerase, and UDP-4-keto-L-rhamnose 4-keto-reductase activities in the cytoplasm
      when expressed in the yeast Saccharomyces cerevisiae. Functional domain analysis
      revealed that the N-terminal region of RHM2 (RHM2-N; amino acids 1-370) has the
      first activity and the C-terminal region of RHM2 (RHM2-C; amino acids 371-667)
      has the two following activities. This suggests that RHM2 converts UDP-d-glucose
      to UDP-L-rhamnose via an UDP-4-keto-6-deoxy-D-glucose intermediate. Site-directed
      mutagenesis of RHM2 revealed that mucilage defects in MUM4-1 and MUM4-2 mutant
      seeds of A. thaliana are caused by abolishment of RHM2 enzymatic activity in the
      mutant strains and furthermore, that the GXXGXX(G/A) and YXXXK motifs are
      important for enzymatic activity. Moreover, a kinetic analysis of purified His(6)
      tagged RHM2-N protein revealed 5.9-fold higher affinity of RHM2 for UDP-D-glucose
      than for dTDP-D-glucose, the preferred substrate for dTDP-D-glucose 4,6
      dehydratase from bacteria. RHM2-N activity is strongly inhibited by UDP-L
      rhamnose, UDP-D-xylose, and UDP but not by other sugar nucleotides, suggesting
      that RHM2 maintains cytoplasmic levels of UDP-D-glucose and UDP-L-rhamnose via
      feedback inhibition by UDP-L-rhamnose and UDP-D-xylose.

PMID- 17190830
TI  - Protein domain-domain interactions and requirements for the negative regulation
      of Arabidopsis CDC48/p97 by the plant ubiquitin regulatory X (UBX) domain
      containing protein, PUX1.
AB  - CDC48/p97 is an essential AAA-ATPase chaperone that functions in numerous diverse
      cellular activities through its interaction with specific adapter proteins. The
      ubiquitin regulatory X (UBX)-containing protein, PUX1, functions to regulate the
      hexameric structure and ATPase activity of AtCDC48. To characterize the
      biochemical mechanism of PUX1 action on AtCDC48, we have defined domains of both
      PUX1 and AtCDC48 that are critical for interaction and oligomer disassembly.
      Binding of PUX1 to AtCDC48 was mediated through a region containing both the UBX
      domain and the immediate C-terminal flanking amino acids (UBX-C). Like other UBX
      domains, the primary binding site for the UBX-C of PUX1 is the N(a) domain of
      AtCDC48. Alternative plant PUX protein UBX domains also bind AtCDC48 through the
      N terminus but were found not to be able to substitute for the action imparted by
      the UBX-C of PUX1 in hexamer disassembly, suggesting unique features for the UBX
      C of PUX1. We propose that the PUX1 UBX-C domain modulates a second binding site
      on AtCDC48 required for the N-terminal domain of PUX1 to interact with and
      promote dissociation of the AtCDC48 hexamer. Utilizing Atcdc48 ATP hydrolysis and
      binding mutants, we demonstrate that PUX1 binding was not affected but that
      hexamer disassembly was significantly influenced by the ATP status of AtCDC48.
      ATPase activity in both the D1 and the D2 domains was critical for PUX1-mediated
      AtCDC48 hexamer disassembly. Together these results provide new mechanistic
      insight into how the hexameric status and ATPase activity of AtCDC48 are
      modulated.

PMID- 17190831
TI  - Caveolin-1 tyrosine phosphorylation enhances paclitaxel-mediated cytotoxicity.
AB  - Caveolin-1 (CAV1), a highly conserved membrane-associated protein, is a putative
      regulator of cellular transformation. CAV1 is localized in the plasmalemma,
      secretory vesicles, Golgi, mitochondria, and endoplasmic reticulum membrane and
      associates with the microtubule cytoskeleton. Taxanes such as paclitaxel (Taxol)
      are potent anti-tumor agents that repress the dynamic instability of microtubules
      and arrest cells in the G(2)/M phase. Src phosphorylation of Tyr-14 on CAV1
      regulates its cellular localization and function. We report that phosphorylation
      of CAV1 on Tyr-14 regulates paclitaxel-mediated apoptosis in MCF-7 breast cancer
      cells. Befitting its role as a multitasking molecule, we show that CAV1
      sensitizes cells to apoptosis by regulating cell cycle progression and activation
      of the apoptotic signaling molecules BCL2, p53, and p21. We demonstrate that
      phosphorylated CAV1 triggers apoptosis by inactivating BCL2 and increasing
      mitochondrial permeability more efficiently than non-phosphorylated CAV1.
      Furthermore, expression of p21, which correlates with taxane sensitivity, is
      regulated by CAV1 phosphorylation in a p53-dependent manner. Collectively, our
      findings underscore the importance of CAV1 phosphorylation in apoptosis and
      suggest that events that negate CAV1 tyrosine phosphorylation may contribute to
      anti-microtubule drug resistance.

PMID- 17190832
TI  - Arabidopsis isochorismate synthase functional in pathogen-induced salicylate
      biosynthesis exhibits properties consistent with a role in diverse stress
      responses.
AB  - Salicylic acid (SA) is a phytohormone best known for its role in plant defense.
      It is synthesized in response to diverse pathogens and responsible for the large
      scale transcriptional induction of defense-related genes and the establishment of
      systemic acquired resistance. Surprisingly, given its importance in plant
      defense, an understanding of the underlying enzymology is lacking. In Arabidopsis
      thaliana, the pathogen-induced accumulation of SA requires isochorismate synthase
      (AtICS1). Here, we show that AtICS1 is a plastid-localized, stromal protein using
      chloroplast import assays and immunolocalization. AtICS1 acts as a monofunctional
      isochorismate synthase (ICS), catalyzing the conversion of chorismate to
      isochorismate (IC) in a reaction that operates near equilibrium (K(eq) = 0.89).
      It does not convert chorismate directly to SA (via an IC intermediate) as does
      Yersinia enterocolitica Irp9. Using an irreversible coupled spectrophotometric
      assay, we found that AtICS1 exhibits an apparent K(m) of 41.5 mum and k(cat) =
      38.7 min(-1) for chorismate. This affinity for chorismate would allow it to
      successfully compete with other pathogen-induced, chorismate-utilizing enzymes.
      Furthermore, the biochemical properties of AtICS1 indicate its activity is not
      regulated by light-dependent changes in stromal pH, Mg(2+), or redox and that it
      is remarkably active at 4 degrees C consistent with a role for SA in cold
      tolerant growth. Finally, our analyses support plastidic synthesis of stress
      induced SA with the requirement for one or more additional enzymes responsible
      for the conversion of IC to SA, because non-enzymatic conversion of IC to SA
      under physiological conditions was negligible.

PMID- 17190833
TI  - Structure of eIF3b RNA recognition motif and its interaction with eIF3j:
      structural insights into the recruitment of eIF3b to the 40 S ribosomal subunit.
AB  - Mammalian eIF3 is a 700-kDa multiprotein complex essential for initiation of
      protein synthesis in eukaryotic cells. It consists of 13 subunits (eIF3a to -m),
      among which eIF3b serves as a major scaffolding protein. Here we report the
      solution structure of the N-terminal RNA recognition motif of human eIF3b (eIF3b
      RRM) determined by NMR spectroscopy. The structure reveals a noncanonical RRM
      with a negatively charged surface in the beta-sheet area contradictory with
      potential RNA binding activity. Instead, eIF3j, which is required for stable 40 S
      ribosome binding of the eIF3 complex, specifically binds to the rear alpha
      helices of the eIF3b-RRM, opposite to its beta-sheet surface. Moreover, we
      identify that an N-terminal 69-amino acid peptide of eIF3j is sufficient for
      binding to eIF3b-RRM and that this interaction is essential for eIF3b-RRM
      recruitment to the 40 S ribosomal subunit. Our results provide the first
      structure of an important subdomain of a core eIF3 subunit and detailed insights
      into protein-protein interactions between two eIF3 subunits required for stable
      eIF3 recruitment to the 40 S subunit.

PMID- 17190834
TI  - Crystal structure of the rac activator, Asef, reveals its autoinhibitory
      mechanism.
AB  - The Rac-specific guanine nucleotide exchange factor (GEF) Asef is activated by
      binding to the tumor suppressor adenomatous polyposis coli mutant, which is found
      in sporadic and familial colorectal tumors. This activated Asef is involved in
      the migration of colorectal tumor cells. The GEFs for Rho family GTPases contain
      the Dbl homology (DH) domain and the pleckstrin homology (PH) domain. When Asef
      is in the resting state, the GEF activity of the DH-PH module is intramolecularly
      inhibited by an unidentified mechanism. Asef has a Src homology 3 (SH3) domain in
      addition to the DH-PH module. In the present study, the three-dimensional
      structure of Asef was solved in its autoinhibited state. The crystal structure
      revealed that the SH3 domain binds intramolecularly to the DH domain, thus
      blocking the Rac-binding site. Furthermore, the RT-loop and the C-terminal region
      of the SH3 domain interact with the DH domain in a manner completely different
      from those for the canonical binding to a polyproline-peptide motif. These
      results demonstrate that the blocking of the Rac-binding site by the SH3 domain
      is essential for Asef autoinhibition. This may be a common mechanism in other
      proteins that possess an SH3 domain adjacent to a DH-PH module.

PMID- 17190836
TI  - Monocytes give rise to mucosal, but not splenic, conventional dendritic cells.
AB  - The mononuclear phagocyte (MP) system is a body-wide macrophage (MPhi) and
      dendritic cell (DC) network, which contributes to tissue homeostasis,
      inflammation, and immune defense. The in vivo origins of MPs remain poorly
      understood. Here, we use an adoptive precursor cell transfer strategy into MP
      depleted mice to establish the in vivo differentiation sequence from a recently
      identified MPhi/DC-restricted bone marrow (BM) precursor (MDP) via BM and blood
      intermediates to peripheral MPhis and DCs. We show that MDPs are in vivo
      precursors of BM and blood monocytes. Interestingly, grafted Gr1high
      "inflammatory" blood monocytes shuttle back to the BM in the absence of
      inflammation, convert into Gr1low monocytes, and contribute further to MP
      generation. The grafted monocytes give rise to DCs in the intestinal lamina
      propria and lung, but not to conventional CD11chigh DCs in the spleen, which
      develop during homeostasis from MDPs without a monocytic intermediate.

PMID- 17190837
TI  - A critical role for the autophagy gene Atg5 in T cell survival and proliferation.
AB  - Macroautophagy (hereafter referred to as autophagy) is a well-conserved
      intracellular degradation process. Recent studies examining cells lacking the
      autophagy genes Atg5 and Atg7 have demonstrated that autophagy plays essential
      roles in cell survival during starvation, in innate cell clearance of microbial
      pathogens, and in neural cell maintenance. However, the role of autophagy in T
      lymphocyte development and survival is not known. Here, we demonstrate that
      autophagosomes form in primary mouse T lymphocytes. By generating Atg5-/-
      chimeric mice, we found that Atg5-deficient T lymphocytes underwent full
      maturation. However, the numbers of total thymocytes and peripheral T and B
      lymphocytes were reduced in Atg5 chimeras. In the periphery, Atg5-/- CD8+ T
      lymphocytes displayed dramatically increased cell death. Furthermore, Atg5-/-
      CD4+ and CD8+ T cells failed to undergo efficient proliferation after TCR
      stimulation. These results demonstrate a critical role for Atg5 in multiple
      aspects of lymphocyte development and function and suggest that autophagy may be
      essential for both T lymphocyte survival and proliferation.

PMID- 17190838
TI  - An essential role for RasGRP1 in mast cell function and IgE-mediated allergic
      response.
AB  - Cross-linking of the FcepsilonRI activates the phosphatidyl inositol 3 kinase
      (PI3K) and mitogen-activated protein kinase pathways. Previous studies
      demonstrate that Ras guanyl nucleotide-releasing protein (RasGRP)1 is essential
      in T cell receptor-mediated Ras-Erk activation. Here, we report that RasGRP1
      plays an important role in FcepsilonRI-mediated PI3K activation and mast cell
      function. RasGRP1-deficient mice failed to mount anaphylactic allergic reactions.
      RasGRP1-/- mast cells had markedly reduced degranulation and cytokine production.
      Although FcepsilonRI-mediated Erk activation was normal, PI3K activation was
      diminished. Consequently, activation of Akt, PIP3-dependent kinase, and protein
      kinase C delta was defective. Expression of a constitutively active form of N-Ras
      could rescue the degranulation defect and Akt activation. We further demonstrated
      that RasGRP1-/- mast cells were defective in granule translocation, microtubule
      formation, and RhoA activation. Our results identified RasGRP1 as an essential
      regulator of mast cell function.

PMID- 17190839
TI  - Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and
      drives the survival of CD4+ central memory T cells.
AB  - The molecular events involved in the establishment and maintenance of CD4+
      central memory and effector memory T cells (TCM and TEM, respectively) are poorly
      understood. In this study, we demonstrate that ex vivo isolated TCM are more
      resistant to both spontaneous and Fas-induced apoptosis than TEM and have an
      increased capacity to proliferate and persist in vitro. Using global gene
      expression profiling, single cell proteomics, and functional assays, we show that
      the survival of CD4+ TCM depends, at least in part, on the activation and
      phosphorylation of signal transducer and activator of transcription 5a (STAT5a)
      and forkhead box O3a (FOXO3a). TCM showed a significant increase in the levels of
      phosphorylation of STAT5a compared with TEM in response to both IL-2 (P<0.04) and
      IL-7 (P<0.002); the latter is well known for its capacity to enhance T cell
      survival. Moreover, ex vivo TCM express higher levels of the transcriptionally
      inactive phosphorylated forms of FOXO3a and concomitantly lower levels of the
      proapoptotic FOXO3a target, Bim. Experiments aimed at blocking FOXO3a
      phosphorylation confirmed the role of this phosphoprotein in protecting TCM from
      apoptosis. Our results provide, for the first time in humans, an insight into
      molecular mechanisms that could be responsible for the longevity and persistence
      of CD4+ TCM.

PMID- 17190842
TI  - Livedoid skin reaction probably due to imatinib therapy.
AB  - OBJECTIVE: To report 3 cases of skin rash with a peculiar livedoid pattern that
      were probably associated with imatinib therapy. CASE SUMMARY: In the first case,
      a 74-year-old male diagnosed with Philadelphia chromosome-positive (Ph+) chronic
      myeloid leukemia (CML), treated with imatinib 400 mg/day, developed a skin
      eruption with a livedoid pattern. Systemic corticosteroids were started, and skin
      lesions improved. The second case involved a 66-year-old male with Ph+ CML who
      was treated with imatinib 600 mg/day. After initiation of this treatment, he
      developed a skin rash with a livedoid pattern. The drug treatment was
      discontinued and then reintroduced. Topical corticosteroid treatment was started,
      resulting in total remission of the skin lesions. When the imatinib dose was
      progressively reintroduced, the skin lesions recurred. The patient died as a
      result of the progression of his disease. In the third case, a 43-year-old male
      with Ph+ acute lymphoblastic leukemia was treated with imatinib 600 mg/day. After
      a few days of treatment, the patient developed a skin rash with a livedoid
      pattern. He died as a result of probable septic shock. DISCUSSION: Imatinib is a
      tyrosine kinase receptor inhibitor that inhibits BCR/ABL tyrosine kinase. There
      have been several published articles on cutaneous adverse reactions related to
      imatinib therapy. The most common cutaneous adverse event of imatinib is a rash
      with variable clinical presentation. The Naranjo probability scale indicated a
      probable relationship between imatinib and the rash in all 3 cases reported here.
      CONCLUSIONS: Adverse reactions to imatinib that affect the skin occur frequently.
      They are strongly dose dependent, self-limiting, or easily managed by lowering
      the dose of imatinib and, if necessary, prescribing short-term therapy with a
      systemic corticosteroid. Clinicians should monitor patients taking imatinib and
      institute treatment quickly if a rash develops.

PMID- 17190840
TI  - DNA polymerase eta is the sole contributor of A/T modifications during
      immunoglobulin gene hypermutation in the mouse.
AB  - Mutations at A/T bases within immunoglobulin genes have been shown to be
      generated by a repair pathway involving the DNA-binding moiety of the mismatch
      repair complex constituted by the MSH2-MSH6 proteins, together with DNA
      polymerase eta (pol eta). However, residual A/T mutagenesis is still observed
      upon inactivation in the mouse of each of these factors, suggesting that the
      panel of activities involved might be more complex. We reported previously
      (Delbos, F., A. De Smet, A. Faili, S. Aoufouchi, J.-C. Weill, and C.-A. Reynaud.
      2005. J. Exp. Med. 201:1191-1196) that residual A/T mutagenesis in pol eta
      deficient mice was likely contributed by another enzyme not normally involved in
      hypermutation, DNA polymerase kappa, which is mobilized in the absence of the
      normal polymerase partner. We report the complete absence of A/T mutations in
      MSH2-pol eta double-deficient mice, thus indicating that the residual A/T
      mutagenesis in MSH2-deficient mice is contributed by pol eta, now recruited by
      uracil N-glycosylase, the second DNA repair pathway involved in hypermutation. We
      propose that this particular recruitment of pol eta corresponds to a profound
      modification of the function of uracil glycosylase in the absence of the mismatch
      repair complex, suggesting that MSH2-MSH6 actively prevent uracil glycosylase
      from error-free repair during hypermutation. pol eta thus appears to be the sole
      contributor of A/T mutations in the normal physiological context.

PMID- 17190841
TI  - Somatic hypermutation: activation-induced deaminase for C/G followed by
      polymerase eta for A/T.
AB  - Somatic hypermutation (SHM) introduces nucleotide substitutions into
      immunoglobulin variable (Ig V) region genes at all four bases, but the mutations
      at C/G and A/T pairs are achieved by distinct mechanisms. Mutations at C/G pairs
      are a direct consequence of the C-->U deamination catalyzed by activation-induced
      deaminase (AID). Mutations at A/T pairs, however, require a second mutagenic
      process that occurs during patch repair of the AID-generated U/G mismatch.
      Several DNA polymerases have been proposed to play a role in SHM, but
      accumulating evidence indicates that the mutations at A/T are overwhelmingly
      achieved by recruitment of DNA polymerase eta.

PMID- 17190843
TI  - Rationale for dipeptidyl peptidase 4 inhibitors: a new class of oral agents for
      the treatment of type 2 diabetes mellitus.
AB  - OBJECTIVE: To review advances in understanding the pathophysiologic basis of type
      2 diabetes mellitus and the pharmacology and mechanism of action of dipeptidyl
      peptidase 4 (DPP-4) inhibition in correcting the underlying defects in glycemic
      control. DATA SOURCES: Articles were identified through MEDLINE for the period
      1966 through November 2006. Abstracts and presentations from the American
      Diabetes Association Scientific Sessions and the European Association for the
      Study of Diabetes (2002-2006) were also searched for scientific reports on DPP-4
      inhibitors. STUDY SELECTION AND DATA EXTRACTION: Abstracts, original clinical and
      preclinical research reports, and review articles published in the English
      language were identified for review. Literature discussing glucose regulation,
      incretin hormones, type 2 diabetes pathophysiology, and DPP-4 inhibition were
      evaluated and selected based on consideration of their support for the proof of
      concept, mechanistic and in vivo findings, and timeliness. DATA SYNTHESIS: The
      search for new and effective therapies for type 2 diabetes has led to the
      identification of a novel therapeutic target, the incretin hormones, which play a
      role in mediating glucose homeostasis via effects on glucagon and insulin
      secretion from pancreatic islet alpha- and beta-cells, respectively. The
      incretins' glucagon-like peptide-1 and glucose-dependent insulinotropic
      polypeptide are rapidly inactivated by the enzyme DPP-4. DPP-4 inhibitor agents
      act by blocking the active site of DPP-4, thereby preventing inactivation of and
      prolonging the duration of action of incretins, which in turn helps to correct
      the defective insulin and glucagon secretion that marks type 2 diabetes. Clinical
      studies to date indicate that DPP-4 inhibitors effectively stimulate insulin
      secretion, suppress glucagon release, and improve glucose control in patients
      with type 2 diabetes. These agents are well tolerated and have a low incidence of
      adverse effects. CONCLUSIONS: The DPP-4 inhibitors are novel agents for the
      treatment of type 2 diabetes. Compounds under development in this new class of
      oral antidiabetic drugs may be free of the limitations of current therapies.

PMID- 17190844
TI  - N-acetylcysteine and sodium bicarbonate versus N-acetylcysteine and standard
      hydration for the prevention of radiocontrast-induced nephropathy following
      coronary angiography.
AB  - BACKGROUND: Radiocontrast-induced nephropathy (RCIN) is thought to be caused by
      renal ischemia and direct toxic effects on renal tubular cells brought on by
      contrast media. The combination of N-acetylcysteine (NAC) and hydration fluids
      (NaCl 0.9% or 0.45%) has been shown to reduce these deleterious effects and is
      commonly given prior to coronary angiography. The use of bicarbonate as the
      hydration anion has been shown to confer additional RCIN protection compared with
      that of saline. However, limited data are available regarding whether sodium
      bicarbonate hydration, proven to be beneficial alone, can further improve
      outcomes when given with NAC. OBJECTIVE: To compare the incidence of RCIN in
      patients undergoing coronary angiography after pretreatment with NAC plus sodium
      bicarbonate hydration or NAC plus standard hydration (NaCl 0.9% or 0.45%).
      METHODS: A retrospective, single-center study evaluated 96 patients who underwent
      coronary angiography from January 2002 to December 2005. Data were collected
      through electronic chart reviews. RESULTS: Forty-seven patients received NAC and
      sodium bicarbonate for hydration and 49 received NAC and standard hydration.
      Baseline characteristics between the 2 groups were similar. All patients received
      at least one 600 mg oral dose of NAC before angiography was performed. RCIN was
      defined as impairment of renal function occurring within 72 hours of
      administering contrast media, indicated by an absolute increase in the serum
      creatinine level of 0.5 mg/dL or more. A total of 12.2% of the patients receiving
      NAC and standard hydration developed RCIN, versus 14.9% of the patients in the
      NAC and sodium bicarbonate group (p = 0.713). CONCLUSIONS: The addition of sodium
      bicarbonate to NAC does not appear to confer additional protection against the
      development of RCIN. Prospective, randomized, placebo-controlled trials are
      warranted to definitively determine how this combination compares with NAC and
      standard hydration in preventing RCIN.

PMID- 17190845
TI  - Oral varenicline for smoking cessation.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of
      varenicline and provide a review of relevant clinical data. DATA SOURCES: A
      MEDLINE search (2001-December 2006) was conducted using the key words varenicline
      and nicotine replacement therapy for clinical trials limited to human subjects
      and published in English. STUDY SELECTION AND DATA EXTRACTION: All available
      human trials of varenicline were selected for review. References cited in
      identified articles were used for additional citations. DATA SYNTHESIS:
      Varenicline selectively targets the alpha4beta2 nicotine receptors in the brain
      that are responsible for cravings and withdrawal associated with nicotine use and
      dependence. Maximal plasma concentration occurs within 3-4 hours after
      administration and, after multiple doses, a steady-state concentration is reached
      within 4 days. Varenicline has a half-life of 24 hours. Oral bioavailability is
      not affected by food or time of administration. It exhibits linear
      pharmacokinetics and low plasma protein binding (< or =20%) regardless of a
      patient's age and renal status. It can be administered once daily. Dosage
      adjustments are not required in patients with hepatic insufficiency, but
      adjustments may be necessary in patients with severe renal insufficiency.
      Clinically significant drug-drug interactions have not been observed with
      varenicline or co-inhibitors of the human organic cation transporter, which
      mediates renal secretion of varenicline. Substrates such as warfarin, digoxin,
      cimetidine, metformin, bupropion, and transdermal nicotine do not alter
      pharmacokinetic parameters when coadministered with varenicline. In vitro studies
      have not demonstrated alterations in cytochrome P450 enzyme parameters.
      Varenicline's safety with coadministration of nicotine replacement products has
      not been well established. CONCLUSIONS: Varenicline is an effective oral agent
      for smoking cessation.

PMID- 17190846
TI  - The role of olanzapine in the treatment of anorexia nervosa.
AB  - OBJECTIVE: To evaluate the role of olanzapine in the treatment of anorexia
      nervosa. DATA SOURCES: Literature was obtained through searches of MEDLINE (1966
      December 2006), EMBASE (1980-4th Quarter 2006), and PsycINFO (1985-December 2006)
      and a bibliographic review of published articles. Key terms used in the searches
      included anorexia nervosa, antipsychotics, eating disorders, olanzapine, and
      Zyprexa. STUDY SELECTION AND DATA EXTRACTION: All English language articles that
      were identified from the search were evaluated. All primary literature was
      included in the review. DATA SYNTHESIS: In several case reports and most clinical
      trials, patients with anorexia nervosa successfully gained weight while being
      treated with olanzapine. Moreover, many patients treated with olanzapine achieved
      a healthy body weight. Case reports and trials identified additional benefits of
      olanzapine, including reduction in delusional thinking; improvement in body
      image, sleep, depressive symptoms, adherence to treatment, and eating-disorder
      symptoms; and decreased agitation and premeal anxiety. CONCLUSIONS: Preliminary
      evidence supports the use of olanzapine for treatment of anorexia nervosa by
      demonstrating that olanzapine 2.5-15 mg daily promotes weight gain and has
      positive effects on associated psychological symptoms. Limitations of the
      reported data include small sample size, low completion rate in clinical trials,
      and open-label trial design. Although olanzapine appears to have a potential role
      in the treatment of anorexia nervosa that has been unresponsive to other therapy,
      randomized, placebo-controlled studies with larger sample sizes are necessary to
      establish its role in therapy.

PMID- 17190848
TI  - Botulinum toxin A in the treatment of sialorrhea.
AB  - OBJECTIVE: To review the efficacy and safety of botulinum toxin A (BTX) in the
      treatment of sialorrhea. DATA SOURCES: A PubMed search and reference list review
      was performed to find clinical trials on BTX in the treatment of sialorrhea. The
      search was limited to English-language trials involving human subjects. Articles
      from 1965 to October 2006 were searched, using key words botulinum, botulinum
      toxin, Botox, sialorrhea, saliva, salivary gland, and drooling. STUDY SELECTION
      AND DATA EXTRACTION: Reports of 15 studies were found on BTX in the treatment of
      sialorrhea in human subjects. Four controlled trials are presented in detail, and
      11 uncontrolled studies are summarized. DATA SYNTHESIS: One controlled trial
      found that BTX caused significant reductions in patients' severity and frequency
      of drooling compared with placebo. Another found significant saliva reductions in
      the treatment group receiving the highest dose of BTX but found no subjective
      improvement compared with the placebo group. A third study comparing BTX with
      placebo found significant improvements in subjective and objective measures of
      drooling in the treatment group. A fourth controlled trial found significant
      reductions from baseline levels of drooling after patients received BTX
      injections. Similar efficacy was found between the BTX and scopolamine treatment
      groups. CONCLUSIONS: Evidence indicates that BTX is a safe and effective
      treatment for sialorrhea. More research is needed to determine the ideal dose,
      injection location, and technique of BTX injections.

PMID- 17190847
TI  - Brand versus generic alendronate: gastrointestinal effects measured by resource
      utilization.
AB  - BACKGROUND: Adverse reactions related to the upper gastrointestinal tract (UGIT)
      that are associated with generic alendronate formulations may differ from those
      associated with the brand drug. OBJECTIVE: To test the hypothesis that adverse
      UGIT effects of alendronate formulations may differ between generic and brand
      products. METHODS: We conducted a database health resource utilization analysis
      of UGIT outcomes in patients who started treatment with generic or brand
      alendronate formulations during 2001-2005. We included 6962 patients who were
      treated continuously for 3 months with 1 of 4 alendronate formulations: brand 10
      mg/day (Merck, Sharpe & Dohme, n = 1418), generic A 10 mg/day (Teva, Israel, n =
      650), generic B 10 mg/day (Unipharm, Israel, n = 628), and brand 70 mg/wk (n =
      4266). In these patients, who had neither filled a prescription for alendronate
      nor had any gastrointestinal problems in the year preceding the study, we
      compared incidence rates of new use of gastric medications (H2-blockers, proton
      pump inhibitors, or antacids), gastroenterology visits, endoscopies, and hospital
      admissions. RESULTS: Incident rate ratios (IRR) for treatment discontinuation
      were higher with both daily generic products (IRR 1.3; 95% CI 1.04 to 1.63).
      Adherence (medication possession ratio [MPR] >80%) was better with brand 10
      mg/day (IRR 1.19; 95% CI 1.11 to 1.27). All comparisons were adjusted for use of
      concurrent corticosteroids, nonsteroidal antiinflammatory drugs, and potassium
      supplements. Hospitalization rates (2.7-3.2%) were similar in all groups. New use
      of gastric medications (3.4-4.9%) was lower with brand 10 mg/day (IRR 0.71; 95%
      CI 0.53 to 0.95). Rates of UGIT endoscopy (n = 49) in patients receiving 10 mg
      were 0.6% (brand), 1.1% (generic A), and 1.6% (generic B), with generic B higher
      (IRR 2.88; 95% CI 1.14 to 7.29) in the entire cohort, but not among new users (n
      = 273) of gastric drugs (IRR 2.46; 95% CI 0.55 to 11.05). Endoscopic findings
      were normal in 22 patients, hiatal hernia with no mucosal lesion was present in
      10 patients, and there was mild-to-moderate esophagitis or gastritis in 17
      patients; there were no significant differences among the formulations.
      CONCLUSIONS: We found insufficient evidence to indicate major differences in UGIT
      adverse effects related to use of daily generic, as compared with brand,
      alendronates.

PMID- 17190849
TI  - Adjunctive aripiprazole in bipolar I depression.
AB  - BACKGROUND: Aripiprazole has demonstrated efficacy in treatment of bipolar mania,
      as well as in the maintenance treatment of bipolar disorder. There has been only
      one report supporting a role for this agent in the depressed phase of the
      illness. OBJECTIVE: To evaluate the effectiveness of adjunctive aripiprazole in
      bipolar I depressed patients who are nonresponders to standard therapy. METHODS:
      Chart records were reviewed for all patients with bipolar I depression, diagnosed
      by Diagnostic and Statistical Manual of Mental Disorders, 4th revision, criteria
      between June 2004 and January 2006 from the Long Beach Veterans Affairs Mood
      Disorders Clinic. Included subjects had experienced moderate to marked depressive
      symptoms (Clinical Global Impression-Bipolar Depression > or =4) despite at least
      2 months of treatment with adequate doses of at least one mood stabilizer. In
      addition, all subjects had been treated subsequently with aripiprazole 15-30
      mg/day added to the existing regimen. Detailed chart notes were used to
      retrospectively rate symptoms. The presence or absence of each symptom was
      recorded before and after aripiprazole augmentation. Based on these data,
      Clinical Global Impression bipolar severity (CGI-BP-S) ratings and CGI-BP
      improvement scores for bipolar I depression were assigned. RESULTS: Ten subjects
      met study criteria. Adjunctive aripiprazole given for 21-110 days resulted in
      significant improvements in CGI-BP-S depression ratings. Seven of 10 patients
      were assigned CGI-BP improvement ratings of much or very much improved. Adverse
      events were mild and included akathisia, nausea, and insomnia. Dose adjustments
      of aripiprazole or the addition of drugs to treat adverse effects excluded
      subjects from further data collection. No patient stopped aripiprazole due to
      adverse effects. CONCLUSIONS: This study adds to a previous report indicating
      beneficial effects of adjunctive aripiprazole in treatment of bipolar I
      depression. Double-blind, placebo-controlled investigations are needed to confirm
      these findings.

PMID- 17190850
TI  - Palifermin: role in the prevention of chemotherapy- and radiation-induced
      mucositis.
AB  - OBJECTIVE: To assess the efficacy, toxicity, and potential cost benefit of
      palifermin in the prevention of chemotherapy- and radiation-induced mucositis.
      DATA SOURCES: MEDLINE and PubMed database searches were conducted (1966-May 2006)
      using the following search terms: palifermin, human keratinocyte growth factor,
      fibroblast growth factor, mucositis, and stomatitis. STUDY SELECTION AND DATA
      EXTRACTION: All published clinical trials and abstracts examining the use of
      palifermin, as well as information from the manufacturer, were included. DATA
      SYNTHESIS: Severe mucositis resulting from anticancer therapies increases
      healthcare expenditures and negatively impacts patients' quality-of-life.
      Radiation therapy to the head and neck, as well as stem cell transplant
      conditioning regimens, have the highest incidence of severe mucositis.
      Consequences include prolonged hospitalization, need for parenteral nutrition,
      increased risk of infection, and severe pain. Palifermin is a recombinant human
      keratinacyte growth factor indicated in patients with hematologic malignancies
      who are undergoing stem cell transplant. In a randomized, placebo-controlled,
      Phase III trial, palifermin significantly reduced the incidence and duration of
      severe mucositis and days of parenteral nutrition and opioid analgesics in
      patients undergoing autologous stem cell transplant. The most common adverse
      effects of palifermin were rash, pruritus, cough, and taste alterations. Data in
      patients with solid tumors are limited, and there is a theoretical risk of
      stimulating tumor growth. CONCLUSIONS: Treatment with palifermin appears to
      decrease the severity and duration of severe mucositis following autologous stem
      cell transplant. Use in these patients appears justified; however, use in non
      stem cell transplant patients should be discouraged until more efficacy and
      toxicity data are available.

PMID- 17190851
TI  - Functional nonsynonymous single nucleotide polymorphisms from the TGF-beta
      protein interaction network.
AB  - Protein complexes mediated by protein-protein interactions are essential for many
      cellular functions. Transforming growth factor (TGF)-beta signaling involves a
      cascade of protein-protein interactions and malfunctioning of this pathway has
      been implicated in human diseases. Using an in silico approach, we analyzed the
      naturally occurring human genetic variations from the proteins involved in the
      TGF-beta signaling (10 TGF-beta proteins and 242 other proteins interacting with
      them) to identify the ones that have potential biological consequences. All
      proteins were searched in the dbSNP database for the presence of nonsynonymous
      single nucleotide polymorphisms (nsSNPs). A total of 118 validated nsSNPs from 63
      proteins were retrieved and analyzed in terms of 1) evolutionary conservation
      status, 2) being located in a functional protein domain or motif, and 3) altering
      putative protein motif or phosphorylation sites. Our results indicated the
      presence of 31 nsSNPs that occurred at evolutionarily conserved residues, 37
      nsSNPs were located in protein domains, motifs, or repeats, and 46 nsSNPs were
      predicted to either create or abolish putative protein motifs or phosphorylation
      sites. We undertook this study to analyze the human genetic variations that can
      affect the protein function and the TGF-beta signaling. The nsSNPs reported in
      here can be characterized by experimental approaches to elucidate their exact
      biological roles and whether they are related to human disease.

PMID- 17190852
TI  - A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and
      human.
AB  - Type 2 diabetes mellitus is the result of a combination of impaired insulin
      secretion with reduced insulin sensitivity of target tissues. There are an
      estimated 150 million affected individuals worldwide, of whom a large proportion
      remains undiagnosed because of a lack of specific symptoms early in this disorder
      and inadequate diagnostics. In this study, NMR-based metabolomic analysis in
      conjunction with multivariate statistics was applied to examine the urinary
      metabolic changes in two rodent models of type 2 diabetes mellitus as well as
      unmedicated human sufferers. The db/db mouse and obese Zucker (fa/fa) rat have
      autosomal recessive defects in the leptin receptor gene, causing type 2 diabetes.
      1H-NMR spectra of urine were used in conjunction with uni- and multivariate
      statistics to identify disease-related metabolic changes in these two animal
      models and human sufferers. This study demonstrates metabolic similarities
      between the three species examined, including metabolic responses associated with
      general systemic stress, changes in the TCA cycle, and perturbations in
      nucleotide metabolism and in methylamine metabolism. All three species
      demonstrated profound changes in nucleotide metabolism, including that of N
      methylnicotinamide and N-methyl-2-pyridone-5-carboxamide, which may provide
      unique biomarkers for following type 2 diabetes mellitus progression.

PMID- 17190853
TI  - The mutational spectrum of type 1 von Willebrand disease: Results from a Canadian
      cohort study.
AB  - In order to evaluate the changes within the VWF gene that might contribute to the
      pathogenesis of type 1 von Willebrand disease (VWD), a large multicenter Canadian
      study was undertaken. We present data from the sequence analysis of the VWF gene
      in 123 type 1 VWD index cases and their families. We have identified putative
      mutations within the VWF gene in 63% (n = 78) of index cases, leaving 37% (n =
      45) with no identified changes. These changes comprise 50 different putative
      mutations: 31 (62%) missense mutations, 8 (16%) changes involving the VWF
      transcriptional regulatory region, 5 (10%) small deletions/insertions, 5 (10%)
      splicing consensus sequence mutations, and 1 nonsense mutation. Twenty-one of the
      index cases had more than one putative VWF mutation identified. We were somewhat
      more likely to identify putative mutations in cases with lower VWF levels, and
      the contribution of other factors, such as ABO blood group, seems more important
      in milder cases. Taken as a whole, our data support a complex spectrum of
      molecular pathology resulting in type 1 VWD. In more severe cases, genetic
      changes are common within the VWF gene and are highly penetrant. In milder cases,
      the genetic determinants are more complex and involve factors outside of the VWF
      gene.

PMID- 17190854
TI  - Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans
      correlates with human B-cell lymphoma aggressiveness.
AB  - A PRoliferation-Inducing TNF Ligand (APRIL) costimulates B-cell activation. When
      overexpressed in mice, APRIL induces B-cell neoplasia, reminiscent of human B
      cell chronic lymphoid leukemia (B-CLL). We analyzed APRIL expression in situ in
      human non-Hodgkin lymphomas. APRIL up-regulation was only observed in high-grade
      B-cell lymphomas, diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma
      (BL). Up-regulation was seen in 46% and 20% of DLBCL and BL, respectively. In
      DLBCL, neutrophils, constitutively producing APRIL and infiltrating the tumor
      tissue, were the main cellular source of APRIL. Rare DLBCL cases showed a
      predominance of histiocytes or mesenchymal cells as APRIL source. APRIL secreted
      by neutrophils accumulated on tumor cells via proteoglycan binding. In addition
      to proteoglycans, DLBCL tumor cells expressed the APRIL signaling receptor, TACI
      and/or BCMA, indicating that these tumor cells are fully equipped to respond to
      APRIL. A retrospective clinical analysis revealed a significant correlation
      between high expression of APRIL in tumor lesions and decreased overall patient
      survival rate. Hence, APRIL produced by inflammatory cells infiltrating lymphoma
      lesions may increase tumor aggressiveness and affect disease outcome.

PMID- 17190855
TI  - Cellular origin and lineage specificity of the JAK2(V617F) allele in polycythemia
      vera.

PMID- 17190857
TI  - Low-dose versus high-dose therapy for Gaucher disease: Goals and markers.

PMID- 17190858
TI  - Platelet transfusion in neonatal alloimmune thrombocytopenia.

PMID- 17190859
TI  - A recurrent in-frame insertion in a CEBPA transactivation domain is a
      polymorphism rather than a mutation that does not affect gene expression
      profiling-based clustering of AML.

PMID- 17190860
TI  - Persistence of functional atrioventricular accessory pathways in postseptated
      embryonic avian hearts: implications for morphogenesis and functional maturation
      of the cardiac conduction system.
AB  - BACKGROUND: During heart development, the ventricular activation sequence changes
      from a base-to-apex to an apex-to-base pattern. We investigated the possibility
      of impulse propagation through remnants of atrioventricular (AV) connections in
      quail hearts. METHODS AND RESULTS: In 86 hearts (group A, HH30-34, n=15; group B,
      HH35-44, n=65; group C, 5 to 6 months, n=6) electrodes were positioned at the
      left atrium, right ventricular base, left ventricular (LV) base, and LV apex. In
      group A, LV base activation preceded LV apex activation in the majority of cases
      (60%; 9 of 15), whereas hearts in group B primarily demonstrated an LV apex-to
      base activation pattern (72%; 47 of 65). Interestingly, in group B, the right
      ventricular base (17%; 11 of 65) or LV base (8%; 5 of 65) exhibited premature
      activation in 25% (16 of 65) of cases, whereas in 26% (17 of 65), the right
      ventricular base or LV base was activated simultaneously with the LV apex.
      Morphological analysis confirmed functional data by showing persistent muscular
      AV connections in embryonic hearts. Interestingly, all myocardial AV connections
      stained positive for periostin, a nonmyocardial marker. Longitudinal analysis
      (HH35-44) demonstrated a decrease in both the number of hearts that exhibited
      premature base activation (P=0.015) and the number (P=0.004) and width (P=0.179)
      of accessory AV pathways with developmental stage in a similar time course. In
      the adult quail hearts, accessory myocardial AV pathways were functionally and
      morphologically absent. CONCLUSIONS: Thus, impulse propagation through persistent
      accessory AV connections remains possible at near-hatching stages (HH44) of
      development, which may provide a substrate for AV reentrant arrhythmias in
      perinatal life. Periostin positivity and absence of AV pathways in the adult
      heart suggest that these connections eventually lose their myocardial phenotype,
      which implicates ongoing AV ring isolation perinatally and postnatally.

PMID- 17190861
TI  - Regional differences in process of care and outcomes for older acute myocardial
      infarction patients in the United States and Ontario, Canada.
AB  - BACKGROUND: Previous comparisons of acute myocardial infarction (AMI) treatment
      between the United States and Canada are limited because they compared selected
      patients from randomized trials, used administrative data that lacked clinical
      detail, or did not consider regional differences in AMI treatment. METHODS AND
      RESULTS: We compared medication use, invasive cardiac procedure use, and 30-day
      risk-standardized mortality rates of 38,886 fee-for-service Medicare
      beneficiaries hospitalized with AMI in the United States and 5634 similarly aged
      patients in Ontario, Canada, from 1998 and 2001. Baseline characteristics and
      illness severity across the US regions and Ontario were not substantially
      different. Cardiac catheterization use in AMI patients was significantly higher
      in the United States compared with Ontario (38.7% versus 16.8%, P<0.001), but
      significant regional variations existed, in which the northeastern United States
      had significantly lower utilization rates (25.6%) compared with other US regions.
      Beta-blocker use among ideal candidates was highest in the northeastern United
      States (77.6% versus 69.7% in the United States as a whole, P<0.001) and
      angiotensin-converting enzyme inhibitor use was highest in Ontario (69.1% versus
      58.2% in the United States, P<0.001). Risk-standardized mortality rates at 30
      days were not substantially different across the regions. CONCLUSIONS: Previous
      studies have suggested a clear divergence in invasive cardiac therapy for AMI
      patients between the United States and Canada on the basis of health care
      financing and structural differences. Our findings of similar treatment patterns
      in the northeastern United States and Ontario suggest that regional practices may
      have a greater impact on treatment patterns than the respective health care
      delivery systems.

PMID- 17190862
TI  - Association of cystatin C with mortality, cardiovascular events, and incident
      heart failure among persons with coronary heart disease: data from the Heart and
      Soul Study.
AB  - BACKGROUND: Serum creatinine and related estimating equations predict
      cardiovascular events and mortality among persons with coronary heart disease
      (CHD). Cystatin C is a novel and sensitive endogenous marker of kidney function.
      Whether cystatin C concentrations are associated with adverse events among
      ambulatory persons with CHD is unknown. METHODS AND RESULTS: Nine hundred ninety
      ambulatory persons with CHD were categorized into quartiles of serum cystatin C
      at inception, with < or = 0.91 mg/L constituting the lowest quartile (I) and > or
      = 1.30 mg/L constituting the highest (IV). Cox proportional hazards models
      evaluated time to all-cause mortality, cardiovascular events (composite of CHD
      death, myocardial infarction, and stroke), and incident heart failure. After a
      median follow-up of 37 months, 132 participants (13%) died, 101 (10%) had
      cardiovascular events, and 57 (7%) had incident heart failure. Compared with
      participants in the lowest cystatin C quartile, those in the highest quartile
      were at increased risk of all-cause mortality (hazard ratio, 3.6; 95% CI, 1.8 to
      7.0), cardiovascular events (hazard ratio, 2.0; 95% CI, 1.0 to 3.8), and incident
      heart failure (hazard ratio, 2.6; 95% CI, 1.0 to 6.9) in analyses adjusted for
      traditional cardiovascular risk factors. Cystatin C in the highest quartile
      predicted similar risk for these outcomes among participants with lower (< or =
      60 mL/min per 1.73 m2) or higher estimated glomerular filtration rate and among
      participants with or without microalbuminuria. CONCLUSIONS: High cystatin C
      concentrations predict substantial increased risks of all-cause mortality,
      cardiovascular events, and incident heart failure among ambulatory persons with
      CHD. This risk is not completely captured by measures of kidney function
      routinely used in clinical practice.

PMID- 17190863
TI  - Hemodynamic modulation of endocardial thromboresistance.
AB  - BACKGROUND: Patients with heart failure are at increased risk for thromboembolic
      events, including stroke. Historically attributed to blood stasis, little is
      known about the adverse effects of elevated chamber filling pressure on
      endocardial function, which could predispose to intracardiac thrombus formation.
      METHODS AND RESULTS: We investigated changes in the expression of thrombomodulin,
      a key component of the anticoagulant protein C pathway, in rats subjected to
      acute atrial pressure overload caused by aortic banding. Acute elevation of left
      atrial filling pressure, without an associated decline in ventricular systolic
      function, caused a 70% inhibition of atrial endocardial thrombomodulin expression
      and resulted in increased local thrombin generation. Targeted restoration of
      atrial thrombomodulin expression with adenovirus-mediated gene transfer
      successfully reduced thrombin generation to baseline levels. In vitro co-culture
      studies revealed that thrombomodulin downregulation is caused by the paracrine
      release of transforming growth factor-beta from cardiac connective tissue in
      response to mechanical stretch. This was confirmed in vivo by administration of a
      neutralizing transforming growth factor-beta antibody, which effectively
      prevented thrombomodulin downregulation during acute pressure overload.
      CONCLUSIONS: These findings suggest that increased hemodynamic load adversely
      affects endocardial function and is a potentially important contributor to
      thromboembolus formation in heart failure.

PMID- 17190864
TI  - Triglycerides and the risk of coronary heart disease: 10,158 incident cases among
      262,525 participants in 29 Western prospective studies.
AB  - BACKGROUND: Many epidemiological studies have reported on associations between
      serum triglyceride concentrations and the risk of coronary heart disease, but
      this association has not been reliably quantified. In the present study, we
      report 2 separate nested case-control comparisons in 2 different prospective,
      population-based cohorts, plus an updated meta-analysis of 27 additional
      prospective studies in general Western populations. METHODS AND RESULTS:
      Measurements were made in a total of 3582 incident cases of fatal and nonfatal
      coronary heart disease and 6175 controls selected from among the 44,237 men and
      women screened in the Reykjavik and the European Prospective Investigation of
      Cancer (EPIC)-Norfolk studies. Repeat measurements were obtained an average of 4
      years apart in 1933 participants in the EPIC-Norfolk Study and an average of 12
      years apart in 379 participants in the Reykjavik study. The long-term stability
      of log-triglyceride values (within-person correlation coefficients of 0.64 [95%
      CI, 0.60 to 0.68] over 4 years and 0.63 [95% CI, 0.57 to 0.70] over 12 years) was
      similar to those of blood pressure and total serum cholesterol. After adjustment
      for baseline values of several established risk factors, the strength of the
      association was substantially attenuated, and the adjusted odds ratio for
      coronary heart disease was 1.76 (95% CI, 1.39 to 2.21) in the Reykjavik study and
      1.57 (95% CI, 1.10 to 2.24) in the EPIC-Norfolk study in a comparison of
      individuals in the top third with those in the bottom third of usual log
      triglyceride values. Similar overall findings (adjusted odds ratio, 1.72; 95% CI,
      1.56 to 1.90) were observed in an updated meta-analysis involving a total of
      10,158 incident coronary heart disease cases from 262,525 participants in 29
      studies. CONCLUSIONS: Available prospective studies in Western populations
      consistently indicate moderate and highly significant associations between
      triglyceride values and coronary heart disease risk. Because these associations
      depend considerably on levels of established risk factors, however, further
      studies are needed to help assess the nature of any independent associations.

PMID- 17190865
TI  - Subclinical coronary and aortic atherosclerosis detected by magnetic resonance
      imaging in type 1 diabetes with and without diabetic nephropathy.
AB  - BACKGROUND: Patients with type 1 diabetes and nephropathy maintain an excess
      cardiovascular mortality compared with diabetic patients with normoalbuminuria.
      We sought to evaluate coronary and aortic atherosclerosis in a cohort of
      asymptomatic type 1 diabetic patients with and without diabetic nephropathy using
      cardiovascular magnetic resonance imaging. METHODS AND RESULTS: In a cross
      sectional study, 136 subjects with long-standing type 1 diabetes without symptoms
      or history of cardiovascular disease, including 63 patients (46%) with
      nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular
      magnetic resonance imaging. All subjects underwent cardiac exercise testing and
      noninvasive tests for peripheral artery disease and autonomic neuropathy.
      Coronary artery stenoses were identified in 10% of subjects with nephropathy
      (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden, expressed as
      right coronary artery mean wall thickness (1.7+/-0.3 versus 1.3+/-0.2 mm;
      P<0.001) and maximum right coronary artery wall thickness (2.2+/-0.5 versus 1.6+/
      0.3 mm; P<0.001), was greater in subjects with nephropathy. The prevalence of
      thoracic (3% versus 0%; P=0.28) and abdominal aortic plaque (22% versus 16%;
      P=0.7) was similar in both groups. Subjects with and without abdominal aortic
      plaques had similar coronary plaque burden. CONCLUSIONS: In asymptomatic type 1
      diabetes, cardiovascular magnetic resonance imaging reveals greater coronary
      plaque burden in subjects with nephropathy compared with those with
      normoalbuminuria.

PMID- 17190866
TI  - Inducible cardiac-restricted expression of enteroviral protease 2A is sufficient
      to induce dilated cardiomyopathy.
AB  - BACKGROUND: Enterovirus infection is a cause of cardiomyopathy. We previously
      demonstrated that enteroviral protease 2A directly cleaves the cytoskeletal
      protein dystrophin. However, the direct effect of protease 2A in enteroviral
      cardiomyopathy is less clear because other viral proteins are also expressed with
      viral infection. METHODS AND RESULTS: A transgenic mouse with inducible cardiac
      restricted expression of enteroviral protease 2A was generated. In the transgenic
      mouse, a tamoxifen-regulated Cre-loxP system, MerCreMer (MCM), was used to induce
      genetic recombination in cardiac myocytes, which led to protease 2A expression.
      Protease 2A and MCM double transgenic (2AxMCM) mice were treated with tamoxifen;
      the controls included 2AxMCM mice treated with diluents for tamoxifen and
      tamoxifen-treated MCM littermates. Protease 2A activity was significantly induced
      after tamoxifen in the 2AxMCM mice compared with controls. Echocardiographic
      analysis demonstrated an increase in left ventricular end-diastolic and end
      systolic chamber size, with decreased fractional shortening in tamoxifen-treated
      2AxMCM mice. There was an increase in heart weight-to-body weight ratio in 2AxMCM
      mice treated with tamoxifen. Only a small increase in interstitial fibrosis and
      inflammation was found in tamoxifen-treated 2AxMCM mice; however, ultrastructural
      analysis demonstrated myofibrillar collapse with abnormalities of intercalated
      discs and sarcolemmal membranes. Evans blue dye-positive myocytes with disruption
      of dystrophin were present in 2AxMCM mice treated with tamoxifen. Disruption of
      dystrophin was also found in cultured myocytes isolated from 2AxMCM mice with Cre
      in the nucleus. CONCLUSIONS: Protease 2A has a significant role in enteroviral
      cardiomyopathy and alone is sufficient to induce dilated cardiomyopathy, which is
      associated with disruption of the sarcolemmal membrane and cleavage of dystrophin
      with protease 2A expression.

PMID- 17190867
TI  - Effects of cardiac resynchronization therapy with or without a defibrillator on
      survival and hospitalizations in patients with New York Heart Association class
      IV heart failure.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) alone or combined with an
      implantable defibrillator (CRT-D) has been shown to improve exercise capacity and
      quality of life and to reduce heart failure (HF) hospitalizations and mortality
      in patients with New York Heart Association (NYHA) class III and IV HF. There is
      concern that the device procedure may destabilize these very ill class IV
      patients. We sought to examine the outcomes of NYHA class IV patients enrolled in
      the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure
      (COMPANION) trial to assess the potential benefits of CRT and CRT-D. METHODS AND
      RESULTS: The COMPANION trial randomized 1520 patients with NYHA class III and IV
      HF to optimal medical therapy, CRT, or CRT-D. In the class IV patients (n=217),
      the primary end point of time to death or hospitalization for any cause was
      significantly improved by both CRT (hazard ratio [HR], 0.64; 95% CI, 0.43 to
      0.94; P=0.02) and CRT-D (HR, 0.62; 95% CI, 0.42 to 0.90; P=0.01). Time to all
      cause death and HF hospitalization was also significantly improved in both CRT
      (HR, 0.57; 95% CI, 0.37 to 0.87; P=0.01) and CRT-D (HR, 0.49; 95% CI, 0.32 to
      0.75; P=0.001) Time to all-cause death trended to an improvement in both CRT (HR,
      0.67; 95% CI, 0.41 to 1.10; P=0.11) and CRT-D (HR, 0.63; 95% CI, 0.39 to 1.03;
      P=0.06). Time to sudden death appeared to be significantly reduced in the CRT-D
      group (HR, 0.27; 95% CI, 0.08 to 0.90; P=0.03). There was a nonsignificant
      reduction in time to HF deaths for both CRT (HR, 0.68; 95% CI, 0.34 to 1.37;
      P=0.28) and CRT-D (HR, 0.79; 95% CI, 0.41 to 1.52; P=0.48). CONCLUSIONS: CRT and
      CRT-D significantly improve time to all-cause mortality and hospitalizations in
      NYHA class IV patients, with a trend for improved mortality. These devices should
      be considered in ambulatory NYHA class IV HF patients similar to those enrolled
      in COMPANION.

PMID- 17190868
TI  - Mutations in the gene encoding filamin A as a cause for familial cardiac valvular
      dystrophy.
AB  - BACKGROUND: Myxomatous dystrophy of the cardiac valves affects approximately 3%
      of the population and remains one of the most common indications for valvular
      surgery. Familial inheritance has been demonstrated with autosomal and X-linked
      transmission, but no specific molecular abnormalities have been documented in
      isolated nonsyndromic forms. We have investigated the genetic causes of X-linked
      myxomatous valvular dystrophy (XMVD) previously mapped to chromosome Xq28.
      METHODS AND RESULTS: A familial and genealogical survey led us to expand the size
      of a large, previously identified family affected by XMVD and to refine the XMVD
      locus to a 2.5-Mb region. A standard positional cloning approach identified a
      P637Q mutation in the filamin A (FLNA) gene in all affected members. Two other
      missense mutations (G288R and V711D) and a 1944-bp genomic deletion coding for
      exons 16 to 19 in the FLNA gene were identified in 3 additional, smaller,
      unrelated families affected by valvular dystrophy, which demonstrates the
      responsibility of FLNA as a cause of XMVD. Among carriers of FLNA mutation, the
      penetrance of the disease was complete in men and incomplete in women. Female
      carriers could be mildly affected, and the severity of the disease was highly
      variable among mutation carriers. CONCLUSIONS: Our data demonstrate that FLNA is
      the first gene known to cause isolated nonsyndromic MVD. This is the first step
      to understanding the pathophysiological mechanisms of the disease and to defining
      pathways that may lead to valvular dystrophy. Screening for FLNA mutations could
      be important for families affected by XMVD to provide adequate follow-up and
      genetic counseling.

PMID- 17190869
TI  - Adenylyl cyclase isoform v mediates renin release from juxtaglomerular cells.
AB  - We have shown previously that decreasing intracellular calcium in the
      juxtaglomerular cells increases both cAMP formation and renin release. We
      hypothesized that this is because of an interaction between intracellular calcium
      and the calcium-inhibitable isoform of adenylyl cyclase, type-V. We used primary
      cultures of juxtaglomerular cells isolated from C-57/B6 mice at 70% to 80%
      confluence. Western blots were performed on isolated juxtaglomerular cells using
      antibodies against either of the 2 calcium inhibitable isoforms of adenylyl
      cyclase, types-V and -VI. Only the antibody against adenylyl cyclase-V gave us a
      strong band at 120 kDa as expected. Immunolabeling in juxtaglomerular cells with
      confocal microscopy found immunofluorescence for the adenylyl cyclase-V-specific
      antibody compared with either negative controls or cells stained with the
      adenylyl cyclase-VI antibody. Reducing isolated juxtaglomerular intracellular
      calcium with 100 micromol/L of the cytosolic calcium chelator BAPTA-AM stimulated
      both cAMP (3.49+/-0.70 to 10.09+/-0.81 pmol/mL per milligram of protein; P<0.002)
      and renin release (1001.8+/-81.5 to 1648.0+/-139.1 ng of angiotensin I per
      milliliter per hour per milligram of protein; P<0.01). The selective adenylyl
      cyclase-V inhibitor NKY80 completely blocked both BAPTA-AM-stimulated cAMP
      formation and renin release. We conclude that lowering intracellular calcium is
      permissive, allowing an increased activity of the calcium-inhibitable isoform
      adenylyl cyclase-V (but not adenylyl cyclase-VI) in the juxtaglomerular cell,
      producing cAMP, which stimulates renin secretion.

PMID- 17190870
TI  - Evolution and hypertension.

PMID- 17190871
TI  - Ambulatory arterial stiffness index is not a stiffness parameter but a ventriculo
      arterial coupling factor.

PMID- 17190872
TI  - Intrarenal aminopeptidase N inhibition augments natriuretic responses to
      angiotensin III in angiotensin type 1 receptor-blocked rats.
AB  - The renal angiotensin angiotensin type 2 receptor has been shown to mediate
      natriuresis, and angiotensin III, not angiotensin II, may be the preferential
      angiotensin type 2 receptor activator of this response. Angiotensin III is
      metabolized to angiotensin IV by aminopeptidase N. The present study hypothesizes
      that inhibition of aminopeptidase N will augment natriuretic responses to
      intrarenal angiotensin III in angiotension type 1 receptor-blocked rats. Rats
      received systemic candesartan for 24 hours before the experiment. After a 1-hour
      control, cumulative renal interstitial infusion of angiotensin III at 3.5, 7, 14,
      and 28 nmol/kg per minute (each dose for 30 minutes) or angiotensin III combined
      with aminopeptidase N inhibitor PC-18 was administered into 1 kidney. The
      contralateral control kidney received renal interstitial infusion of vehicle. In
      kidneys infused with angiotensin III alone, renal sodium excretion rate increased
      from 0.05+/-0.01 micromol/min in stepwise fashion to 0.11+/-0.01 micromol/min at
      28 nmol/kg per minute of angiotensin III (overall ANOVA F=3.68; P<0.01). In
      angiotensin III combined with PC-18, the renal sodium excretion rate increased
      from 0.05+/-0.01 to 0.32+/-0.08 mumol/min at 28 nmol/kg per minute of angiotensin
      III (overall ANOVA F=6.2; P<0.001). The addition of intrarenal PD-123319, an
      angiotensin type 2 receptor antagonist, to renal interstitial angiotensin III
      plus PC-18 inhibited the natriuretic response. Mean arterial blood pressure and
      renal sodium excretion rate from control kidneys were unchanged by angiotensin
      III +/- PC-18 + PD-123319. Angiotensin III plus PC-18 induced a greater
      natriuretic response than Ang III alone (overall ANOVA F=16.9; P=0.0001).
      Aminopeptidase N inhibition augmented the natriuretic response to angiotensin
      III, suggesting that angiotensin III is a major agonist of angiotensin type 2
      receptor-induced natriuresis.

PMID- 17190874
TI  - Hypothalamic arcuate nucleus mediates the sympathetic and arterial pressure
      responses to leptin.
AB  - Leptin is an adipocyte-derived hormone that plays an important role in the
      regulation of energy homeostasis through its action in the central nervous
      system. Leptin decreases body weight by promoting satiety and increasing
      thermogenesis via increasing sympathetic nerve activity (SNA) to brown adipose
      tissue. Leptin also increases renal SNA and arterial pressure. The arcuate
      nucleus is considered as a major nucleus for leptin action on energy homeostasis.
      We tested whether leptin action in the arcuate nucleus simultaneously activates
      SNA to brown adipose tissue and the kidney. The sympathetic and cardiovascular
      responses to intra-arcuate injection of leptin were compared with those evoked by
      intracerebroventricular administration of leptin in rat. Intracerebroventricular
      administration of leptin (10 mug) caused a significant increase in SNA to brown
      adipose tissue and the kidney. Intracerebroventricular leptin also increased mean
      arterial pressure. Direct injection of leptin (500 ng) into the arcuate nucleus
      increased both brown adipose tissue (254+/-49%; P<0.001 versus vehicle) and renal
      SNA (111+/-31%; P<0.001 versus vehicle). Microinjection of leptin into the
      arcuate nucleus also produced a substantial increase in mean arterial pressure
      (from 82+/-3 to 100+/-7 mm Hg; P=0.02). These data demonstrate that leptin action
      in the arcuate nucleus of the hypothalamus is important for the control of
      sympathetic outflow to both brown adipose tissue and the kidney. These results
      also suggest that the cardiovascular effects of leptin might be evoked by the
      action of this hormone in the arcuate nucleus of the hypothalamus.

PMID- 17190873
TI  - Neurons of the rostral ventrolateral medulla contribute to obesity-induced
      hypertension in rats.
AB  - Activation of the sympathetic nervous system contributes to the pathogenesis of
      obesity-induced hypertension. The present study sought to determine whether
      sympathetic regulatory neurons of the rostral ventrolateral medulla contribute to
      the elevated blood pressure in obese rats. Male Sprague-Dawley rats (350 to 425
      g) were placed on a moderately high-fat diet (32% kcal as fat) or a low-fat (LF)
      diet (10.6% kcal as fat). After 13 weeks, rats fed the moderately high-fat diet
      segregated into obesity-prone (OP) and obesity-resistant (OR) groups based on
      their body weight (OP: 839+/-22 g; OR: 668+/-15 g; LF: 680+/-18 g; n=15 for all
      groups; P<0.01). Under isoflurane anesthesia, baseline mean arterial blood
      pressure was significantly elevated in the OP rats versus the OR and LF rats (OP:
      108+/-2 mm Hg; OR: 100+/-2 mm Hg; LF: 97+/-3 mm Hg; n=7; P<0.05). Inhibition of
      the rostral ventrolateral medulla with bilateral microinjection of the GABA(A)
      receptor agonist muscimol (200 pmol/100 nL) decreased mean arterial blood
      pressure to similar levels across the groups (OP: 49+/-1 mm Hg; OR: 50+/-2 mm Hg;
      LF: 49+/-1 mm Hg), but the magnitude of this decrease was significantly greater
      in the OP versus the OR and LF rats (OP: -58+/-2 mm Hg; OR: -49+/-1 mm Hg; LF: 
      48+/-3 mm Hg; P<0.01). These differences in mean arterial blood pressure cannot
      be explained by changes in vascular reactivity as the ED(50) in response to
      phenylephrine and norepinephrine was similar across the groups. The present
      findings suggest that the elevated sympathetic nerve activity and arterial blood
      pressure in obese rats depends on the tonic activity of rostral ventrolateral
      medulla sympathetic neurons.

PMID- 17190876
TI  - Identification of active central nervous system sites in renal wrap hypertensive
      rats.
AB  - To identify central neurons participating in cardiovascular regulation in
      hypertension, we studied Fos staining, a marker for synaptically activated
      neurons, in adult male normotensive and hypertensive (HT) rats. At 1 and 4 weeks
      after induction of unilateral nephrectomy, renal wrap hypertension mean arterial
      pressure was 138+/-4 mm Hg (n=6) in 1-week HT rats and 159+/-6 mm Hg (n=6) in 4
      week HT rats. Mean arterial pressure was 103+/-2 mm Hg (n=6) in sham-operated,
      normotensive rats. Mean arterial pressure was greater in both HT groups compared
      with normotensive rats, and the mean arterial pressure in 4-week HT rats was
      greater than that in 1-week HT rats. Rats were anesthetized and perfused, brains
      sectioned and processed using a Fos antibody, and the number of Fos
      immunoreactive neurons counted in sections through various brain regions.
      Hypertension of 1 or 4 weeks did not alter the number of Fos immunoreactive
      neurons in the area postrema, the supraoptic nucleus, and the median preoptic
      nucleus. The number of Fos immunoreactive neurons was increased after 1 and 4
      weeks in the nucleus of the solitary tract, both the caudal and ventral lateral
      medulla, and the organum vasculosum of the lamina terminalis. In addition, after
      4 weeks of HT, the number of Fos immunoreactive neurons was increased in the
      parabrachial nucleus and the paraventricular nucleus of the hypothalamus. The
      results indicate central regions active in acute and chronic HT rats and suggest
      certain areas that may be differentially activated depending on the duration of
      the hypertension.

PMID- 17190875
TI  - Reactive oxygen species-dependent hypertension in dopamine D2 receptor-deficient
      mice.
AB  - Dysfunction of D2-like receptors has been reported in essential hypertension.
      Disruption of D2R in mice (D2-/-) results in high blood pressure, and several D2R
      polymorphisms are associated with decreased D2R expression. Because D2R agonists
      have antioxidant activity, we hypothesized that increased blood pressure in D2-/-
      is related to increased oxidative stress. D2-/- mice had increased urinary
      excretion of 8-isoprostane, a parameter of oxidative stress; increased activity
      of reduced nicotinamide-adenine dinucleotide phosphate oxidase in renal cortex;
      increased expression of the reduced nicotinamide-adenine dinucleotide phosphate
      oxidase subunits Nox1, Nox2, and Nox4; and decreased expression of the
      antioxidant enzyme heme-oxygenase-2 in the kidneys, suggesting that regulation of
      reactive oxygen species (ROS) production by D2R involves both pro-oxidant and
      antioxidant systems. Apocynin, a reduced nicotinamide-adenine dinucleotide
      phosphate oxidase inhibitor, or hemin, an inducer of heme oxigenase-1, normalized
      the blood pressure in D2-/- mice. Because D2Rs in the adrenal gland are
      implicated in aldosterone regulation, we evaluated whether alterations in
      aldosterone secretion contribute to ROS production in this model. Urinary
      aldosterone was increased in D2-/- mice and its response to a high-sodium diet
      was impaired. Spirolactone normalized the blood pressure in D2-/- mice and the
      renal expression of Nox1 and Nox4, indicating that the increased blood pressure
      and ROS production are, in part, mediated by impaired aldosterone regulation.
      However, spironolactone did not normalize the excretion of 8-isoprostane and had
      no effect on expression of Nox2 or heme-oxygenase-2. Our results show that the
      D2R is involved in the regulation of ROS production and that, by direct and
      indirect mechanisms, altered D2R function may result in ROS-dependent
      hypertension.

PMID- 17190877
TI  - Hyperuricemia and incidence of hypertension among men without metabolic syndrome.
AB  - The aim of this project was to study the risk of developing hypertension over a 6
      year follow-up in normotensive men with baseline hyperuricemia (serum uric acid
      >7.0 mg/dL) but without diabetes/glucose intolerance or metabolic syndrome. We
      analyzed the data on men without metabolic syndrome or hypertension at baseline
      from the Multiple Risk Factor Intervention Trial. These men (n=3073; age: 35 to
      57 years) were followed for an average of 6 years by annual examinations. Follow
      up blood pressure among those with baseline was consistently higher than among
      those with normal serum uric acid concentration. We used Cox regression models
      for adjustment for the effects of serum creatinine, body mass index, age, blood
      pressure, proteinuria, serum cholesterol and triglycerides, alcohol and tobacco
      use, risk factor interventions, and use of diuretics. In these models,
      normotensive men with baseline hyperuricemia had an 80% excess risk for incident
      hypertension (hazard ratio: 1.81; 95% CI: 1.59 to 2.07) compared with those who
      did not. Each unit increase in serum uric acid was associated with a 9% increase
      in the risk for incident hypertension (hazard ratio: 1.09; 95% CI: 1.02 to 1.17).
      We conclude that the hyperuricemia-hypertension risk relationship is present
      among normotensive middle-aged men without diabetes/glucose intolerance or
      metabolic syndrome.

PMID- 17190880
TI  - The cover. The Supper After the Masked Ball.

PMID- 17190881
TI  - A piece of my mind. A bump in the neck.

PMID- 17190878
TI  - Role of oxidative stress in cardiac hypertrophy and remodeling.

PMID- 17190883
TI  - New 3D imaging software opens new vistas.

PMID- 17190882
TI  - Groups take aim at US preterm birth rate.

PMID- 17190884
TI  - Electronic health records, after-hours care lag in US primary care practices.

PMID- 17190885
TI  - Chronic fatigue syndrome answers sought.

PMID- 17190886
TI  - Refusal of care by patients.

PMID- 17190887
TI  - Refusal of care by patients.

PMID- 17190888
TI  - Refusal of care by patients.

PMID- 17190889
TI  - Refusal of care by patients.

PMID- 17190890
TI  - Medicare requirement for research participation.

PMID- 17190891
TI  - Medicare requirement for research participation.

PMID- 17190892
TI  - Financial disclosure policies of scientific publications.

PMID- 17190893
TI  - Effects of continuing or stopping alendronate after 5 years of treatment: the
      Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.
AB  - CONTEXT: The optimal duration of treatment of women with postmenopausal
      osteoporosis is uncertain. OBJECTIVE: To compare the effects of discontinuing
      alendronate treatment after 5 years vs continuing for 10 years. DESIGN AND
      SETTING: Randomized, double-blind trial conducted at 10 US clinical centers that
      participated in the Fracture Intervention Trial (FIT). PARTICIPANTS: One thousand
      ninety-nine postmenopausal women who had been randomized to alendronate in FIT,
      with a mean of 5 years of prior alendronate treatment. INTERVENTION:
      Randomization to alendronate, 5 mg/d (n = 329) or 10 mg/d (n = 333), or placebo
      (n = 437) for 5 years (1998-2003). MAIN OUTCOME MEASURES: The primary outcome
      measure was total hip bone mineral density (BMD); secondary measures were BMD at
      other sites and biochemical markers of bone remodeling. An exploratory outcome
      measure was fracture incidence. RESULTS: Compared with continuing alendronate,
      switching to placebo for 5 years resulted in declines in BMD at the total hip (
      2.4%; 95% confidence interval [CI], -2.9% to -1.8%; P<.001) and spine (-3.7%; 95%
      CI, -4.5% to -3.0%; P<.001), but mean levels remained at or above pretreatment
      levels 10 years earlier. Similarly, those discontinuing alendronate had increased
      serum markers of bone turnover compared with continuing alendronate: 55.6%
      (P<.001) for C-telopeptide of type 1 collagen, 59.5% (P < .001) for serum n =
      propeptide of type 1 collagen, and 28.1% (P<.001) for bone-specific alkaline
      phosphatase, but after 5 years without therapy, bone marker levels remained
      somewhat below pretreatment levels 10 years earlier. After 5 years, the
      cumulative risk of nonvertebral fractures (RR, 1.00; 95% CI, 0.76-1.32) was not
      significantly different between those continuing (19%) and discontinuing (18.9%)
      alendronate. Among those who continued, there was a significantly lower risk of
      clinically recognized vertebral fractures (5.3% for placebo and 2.4% for
      alendronate; RR, 0.45; 95% CI, 0.24-0.85) but no significant reduction in
      morphometric vertebral fractures (11.3% for placebo and 9.8% for alendronate; RR,
      0.86; 95% CI, 0.60-1.22). A small sample of 18 transilial bone biopsies did not
      show any qualitative abnormalities, with bone turnover (double labeling) seen in
      all specimens. CONCLUSIONS: Women who discontinued alendronate after 5 years
      showed a moderate decline in BMD and a gradual rise in biochemical markers but no
      higher fracture risk other than for clinical vertebral fractures compared with
      those who continued alendronate. These results suggest that for many women,
      discontinuation of alendronate for up to 5 years does not appear to significantly
      increase fracture risk. However, women at very high risk of clinical vertebral
      fractures may benefit by continuing beyond 5 years. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT 00398931.

PMID- 17190894
TI  - Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over
      the past 50 years.
AB  - CONTEXT: Prior estimates of long-term trends in the incidence and severity of
      stroke have varied; trends in lifetime risk have not been reported. OBJECTIVE: To
      determine long-term trends in the incidence, lifetime risk, severity, and 30-day
      mortality of clinical stroke. DESIGN, SETTING, AND PARTICIPANTS: Prospective
      evaluation of the community-based Framingham Study original and offspring
      cohorts. Participants were 9152 men and women free of prevalent stroke and
      undergoing follow-up for up to 50 years over 3 consecutive periods (1950-1977,
      1978-1989, and 1990-2004), with biennial ascertainment of stroke risk factor data
      and active surveillance for incident clinical stroke and cause-specific
      mortality. MAIN OUTCOME MEASURES: Incidence (age-adjusted, sex-specific),
      severity, 30-day mortality, and mortality-adjusted 10-year and lifetime risk of
      stroke in each of the specified periods. RESULTS: There were 1030 incident
      clinical strokes (450 [44%] in men, 629 atherothrombotic brain infarctions [61%])
      in 9152 persons 55 years or older over 174,917 person-years of follow-up. The age
      adjusted incidence of first stroke per 1000 person-years in each of the 3 periods
      was 7.6, 6.2, and 5.3, respectively, in men (P = .02 for trend) and 6.2, 5.8, and
      5.1 in women (P = .01 for trend). The lifetime risk at age 65 years decreased
      from 19.5% to 14.5% in men (P = .11) and from 18.0% to 16.1% in women (P = .61).
      Age-adjusted stroke severity did not vary across periods; however, 30-day
      mortality decreased significantly in men (from 23% to 14%; P = .01) but not
      significantly in women (from 21% to 20%; P = .32). CONCLUSIONS: In this cohort of
      men and women free of prevalent clinical stroke at initial examination, incidence
      of stroke has decreased over the past 50 years but the lifetime risk has not
      declined to the same degree, perhaps due to improved life expectancy. The results
      of this study suggest that improved control of risk factors has lowered stroke
      incidence but emphasize the need for continued primary prevention efforts.

PMID- 17190895
TI  - Long-term proton pump inhibitor therapy and risk of hip fracture.
AB  - CONTEXT: Proton pump inhibitors (PPIs) may interfere with calcium absorption
      through induction of hypochlorhydria but they also may reduce bone resorption
      through inhibition of osteoclastic vacuolar proton pumps. OBJECTIVE: To determine
      the association between PPI therapy and risk of hip fracture. DESIGN, SETTING,
      AND PATIENTS: A nested case-control study was conducted using the General
      Practice Research Database (1987-2003), which contains information on patients in
      the United Kingdom. The study cohort consisted of users of PPI therapy and
      nonusers of acid suppression drugs who were older than 50 years. Cases included
      all patients with an incident hip fracture. Controls were selected using
      incidence density sampling, matched for sex, index date, year of birth, and both
      calendar period and duration of up-to-standard follow-up before the index date.
      For comparison purposes, a similar nested case-control analysis for histamine 2
      receptor antagonists was performed. MAIN OUTCOME MEASURE: The risk of hip
      fractures associated with PPI use. RESULTS: There were 13,556 hip fracture cases
      and 135,386 controls. The adjusted odds ratio (AOR) for hip fracture associated
      with more than 1 year of PPI therapy was 1.44 (95% confidence interval [CI], 1.30
      1.59). The risk of hip fracture was significantly increased among patients
      prescribed long-term high-dose PPIs (AOR, 2.65; 95% CI, 1.80-3.90; P<.001). The
      strength of the association increased with increasing duration of PPI therapy
      (AOR for 1 year, 1.22 [95% CI, 1.15-1.30]; 2 years, 1.41 [95% CI, 1.28-1.56]; 3
      years, 1.54 [95% CI, 1.37-1.73]; and 4 years, 1.59 [95% CI, 1.39-1.80]; P<.001
      for all comparisons). CONCLUSION: Long-term PPI therapy, particularly at high
      doses, is associated with an increased risk of hip fracture.

PMID- 17190896
TI  - Patent foramen ovale and high-altitude pulmonary edema.
AB  - CONTEXT: Individuals susceptible to high-altitude pulmonary edema (HAPE) are
      characterized by exaggerated pulmonary hypertension and arterial hypoxemia at
      high altitude, but the underlying mechanism is incompletely understood. Anecdotal
      evidence suggests that shunting across a patent foramen ovale (PFO) may
      exacerbate hypoxemia in HAPE. OBJECTIVE: We hypothesized that PFO is more
      frequent in HAPE-susceptible individuals and may contribute to more severe
      arterial hypoxemia at high altitude. DESIGN, SETTING, AND PARTICIPANTS: Case
      control study of 16 HAPE-susceptible participants and 19 mountaineers resistant
      to this condition (repeated climbing to peaks above 4000 m and no symptoms of
      HAPE). MAIN OUTCOME MEASURES: Presence of PFO determined by transesophageal
      echocardiography, estimated pulmonary artery pressure by Doppler
      echocardiography, and arterial oxygen saturation measured by pulse oximetry in
      HAPE-susceptible and HAPE-resistant participants at low (550 m) and high altitude
      (4559 m). RESULTS: The frequency of PFO was more than 4 times higher in HAPE
      susceptible than in HAPE-resistant participants, both at low altitude (56% vs
      11%, P = .004; odds ratio [OR], 10.9 [95% confidence interval {CI}, 1.9-64.0])
      and high altitude (69% vs 16%, P = .001; OR, 11.7 [95% CI, 2.3-59.5]). At high
      altitude, mean (SD) arterial oxygen saturation prior to the onset of pulmonary
      edema was significantly lower in HAPE-susceptible participants than in the
      control group (73% [10%] vs 83% [7%], P = .001). Moreover, in the HAPE
      susceptible group, participants with a large PFO had more severe arterial
      hypoxemia (65% [6%] vs 77% [8%], P = .02) than those with smaller or no PFO.
      CONCLUSIONS: Patent foramen ovale was roughly 4 times more frequent in HAPE
      susceptible mountaineers than in participants resistant to this condition. At
      high altitude, HAPE-susceptible participants with a large PFO had more severe
      hypoxemia. We speculate that at high altitude, a large PFO may contribute to
      exaggerated arterial hypoxemia and facilitate HAPE.

PMID- 17190897
TI  - End-of-life care for homeless patients: "she says she is there to help me in any
      situation".
AB  - Homelessness annually affects an estimated 2.3 million to 3.5 million individuals
      living in the United States. Homeless people face difficulties in meeting their
      basic needs. Many have substance abuse problems and mental illness, lack social
      support, and have no medical insurance. These challenges complicate the homeless
      patient's ability to engage in end-of-life advanced planning, adhere to
      medications, and find an adequate site to receive terminal care. Employing a
      multidisciplinary team to care for homeless patients can help address their needs
      and improve care. For patients who continue to use illicit substances while
      receiving end-of-life care, experts recommend scheduling frequent clinic visits,
      using long-acting pain medications, dispensing small quantities of medications at
      a time, and using a written pain agreement. Homeless people are less likely to
      have a surrogate decision maker. Clinicians should have frequent, well-documented
      conversations with these patients about end-of-life wishes. Homeless people can
      rarely use hospice services because they lack the financial resources for
      inpatient hospice and have neither the home nor the social support required for
      home hospice. Developing inpatient palliative care services at hospitals that
      serve many homeless people could improve the end-of-life care homeless people
      receive.

PMID- 17190898
TI  - Palliative care for frail older adults: "there are things I can't do anymore that
      I wish I could".

PMID- 17190899
TI  - Ten vs five years of bisphosphonate treatment for postmenopausal osteoporosis:
      enough of a good thing.

PMID- 17190900
TI  - JAMA patient page. Atrial septal defects.

PMID- 17190901
TI  - Open channel block by Ca2+ underlies the voltage dependence of drosophila TRPL
      channel.
AB  - The light-activated channels of Drosophila photoreceptors transient receptor
      potential (TRP) and TRP-like (TRPL) show voltage-dependent conductance during
      illumination. Recent studies implied that mammalian members of the TRP family,
      which belong to the TRPV and TRPM subfamilies, are intrinsically voltage-gated
      channels. However, it is unclear whether the Drosophila TRPs, which belong to the
      TRPC subfamily, share the same voltage-dependent gating mechanism. Exploring the
      voltage dependence of Drosophila TRPL expressed in S2 cells, we found that the
      voltage dependence of this channel is not an intrinsic property since it became
      linear upon removal of divalent cations. We further found that Ca(2+) blocked
      TRPL in a voltage-dependent manner by an open channel block mechanism, which
      determines the frequency of channel openings and constitutes the sole parameter
      that underlies its voltage dependence. Whole cell recordings from a Drosophila
      mutant expressing only TRPL indicated that Ca(2+) block also accounts for the
      voltage dependence of the native TRPL channels. The open channel block by Ca(2+)
      that we characterized is a useful mechanism to improve the signal to noise ratio
      of the response to intense light when virtually all the large conductance TRPL
      channels are blocked and only the low conductance TRP channels with lower Ca(2+)
      affinity are active.

PMID- 17190902
TI  - Depolarization-induced calcium responses in sympathetic neurons: relative
      contributions from Ca2+ entry, extrusion, ER/mitochondrial Ca2+ uptake and
      release, and Ca2+ buffering.
AB  - Many models have been developed to account for stimulus-evoked [Ca(2+)]
      responses, but few address how responses elicited in specific cell types are
      defined by the Ca(2+) transport and buffering systems that operate in the same
      cells. In this study, we extend previous modeling studies by linking the time
      course of stimulus-evoked [Ca(2+)] responses to the underlying Ca(2+) transport
      and buffering systems. Depolarization-evoked [Ca(2+)](i) responses were studied
      in sympathetic neurons under voltage clamp, asking how response kinetics are
      defined by the Ca(2+) handling systems expressed in these cells. We investigated
      five cases of increasing complexity, comparing observed and calculated responses
      deduced from measured Ca(2+) handling properties. In Case 1, [Ca(2+)](i)
      responses were elicited by small Ca(2+) currents while Ca(2+) transport by
      internal stores was inhibited, leaving plasma membrane Ca(2+) extrusion intact.
      In Case 2, responses to the same stimuli were measured while mitochondrial Ca(2+)
      uptake was active. In Case 3, responses were elicited as in Case 2 but with
      larger Ca(2+) currents that produce larger and faster [Ca(2+)](i) elevations.
      Case 4 included the mitochondrial Na/Ca exchanger. Finally, Case 5 included ER
      Ca(2+) uptake and release pathways. We found that [Ca(2+)](i) responses elicited
      by weak stimuli (Cases 1 and 2) could be quantitatively reconstructed using a
      spatially uniform model incorporating the measured properties of Ca(2+) entry,
      removal, and buffering. Responses to strong depolarization (Case 3) could not be
      described by this model, but were consistent with a diffusion model incorporating
      the same Ca(2+) transport and buffering descriptions, as long as endogenous
      buffers have low mobility, leading to steep radial [Ca(2+)](i) gradients and
      spatially nonuniform Ca(2+) loading by mitochondria. When extended to include
      mitochondrial Ca(2+) release (Case 4) and ER Ca(2+) transport (Case 5), the
      diffusion model could also account for previous measurements of stimulus-evoked
      changes in total mitochondrial and ER Ca concentration.

PMID- 17190904
TI  - Glucagon-like peptide-1 stimulates GABA formation by pancreatic beta-cells at the
      level of glutamate decarboxylase.
AB  - Pancreatic beta-cells are the major extraneural site of glutamate decarboxylase
      expression (GAD). During culture of isolated beta-cells, the GAD product gamma
      aminobutyrate (GABA) is rapidly released in the medium, independently of insulin.
      It is considered as a possible mediator of beta-cell influences on alpha-cells,
      acinar cells, and/or infiltrating lymphocytes. In this perspective, we
      investigated the regulation of GABA release by rat beta-cells during a 24-h
      culture period. Glucose was previously reported to inhibit GABA release by
      diverting cellular GABA to mitochondrial breakdown through activation of GABA
      transferase (GABA-T). In the present study, glucagon-like peptide-1 (GLP-1) was
      shown to stimulate GABA formation at the level of GAD, its effect being
      suppressed by the GAD inhibitor allylglycine and remaining unaltered by the GABA
      T inhibitor gamma-vinyl-GABA. The stimulatory action of GLP-1 is cAMP dependent,
      being reproduced by the adenylate cyclase activator forskolin and the cAMP analog
      N(6)-benzoyladenosine-3',5'-cAMP and inhibited by a PKA inhibitor. It is
      dependent on protein synthesis and associated with an increased expression of
      GAD67 but not GAD65. The GLP-1-induced stimulation of GAD activity in beta-cells
      can elevate medium GABA levels in conditions of glucose-driven intracellular GABA
      breakdown and thus maintain GABA-mediated beta-cell influences on neighboring
      cells.

PMID- 17190903
TI  - Pharmacological dissection and distribution of NaN/Nav1.9, T-type Ca2+ currents,
      and mechanically activated cation currents in different populations of DRG
      neurons.
AB  - Low voltage-activated (LVA) T-type Ca(2+) (I(Ca)T) and NaN/Nav1.9 currents
      regulate DRG neurons by setting the threshold for the action potential. Although
      alterations in these channels have been implicated in a variety of pathological
      pain states, their roles in processing sensory information remain poorly
      understood. Here, we carried out a detailed characterization of LVA currents in
      DRG neurons by using a method for better separation of NaN/Nav1.9 and I(Ca)T
      currents. NaN/Nav1.9 was inhibited by inorganic I(Ca) blockers as follows
      (IC(50), microM): La(3+) (46) > Cd(2+) (233) > Ni(2+) (892) and by mibefradil, a
      non-dihydropyridine I(Ca)T antagonist. Amiloride, however, a preferential Cav3.2
      channel blocker, had no effects on NaN/Nav1.9 current. Using these discriminative
      tools, we showed that NaN/Nav1.9, Cav3.2, and amiloride- and Ni(2+)-resistant
      I(Ca)T (AR-I(Ca)T) contribute differentially to LVA currents in distinct sensory
      cell populations. NaN/Nav1.9 carried LVA currents into type-I (CI) and type-II
      (CII) small nociceptors and medium-Adelta-like nociceptive cells but not in low
      threshold mechanoreceptors, including putative Down-hair (D-hair) and Aalpha/beta
      cells. Cav3.2 predominated in CII-nociceptors and in putative D-hair cells. AR
      I(Ca)T was restricted to CII-nociceptors, putative D-hair cells, and Aalpha/beta
      like cells. These cell types distinguished by their current-signature displayed
      different types of mechanosensitive channels. CI- and CII-nociceptors displayed
      amiloride-sensitive high-threshold mechanical currents with slow or no
      adaptation, respectively. Putative D-hair and Aalpha/beta-like cells had low
      threshold mechanical currents, which were distinguished by their adapting
      kinetics and sensitivity to amiloride. Thus, subspecialized DRG cells express
      specific combinations of LVA and mechanosensitive channels, which are likely to
      play a key role in shaping responses of DRG neurons transmitting different
      sensory modalities.

PMID- 17190905
TI  - Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid
      dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes.
AB  - A clinically employed antihyperlipidemic drug, bezafibrate, has been
      characterized as a PPAR(alpha, -gamma, and -delta) pan-agonist in vitro. Recent
      extended trials have highlighted its antidiabetic properties in humans. However,
      the underlying molecular mechanism is not fully elucidated. The present study was
      designed to explore potential regulatory mechanisms of intracellular
      glucocorticoid reactivating enzyme, 11beta-HSD1 and anti-diabetic hormone,
      adiponectin by bezafibrate in murine adipose tissue, and cultured adipocytes.
      Treatment of db/db mice with bezafibrate significantly ameliorated hyperglycemia
      and insulin resistance, accompanied by a marked reduction of triglyceride and
      nonesterified fatty acids. Despite equipotent in lipid-lowering effects, another
      fibrate, fenofibrate, did not show such beneficial effects on glycemic control.
      Treatment of bezafibrate caused a marked decrease in the mRNA level of 11beta
      HSD1 preferentially in adipose tissue of db/db mice (-47%, P<0.05), concomitant
      with a significant increase in plasma adiponectin level (+37%, P<0.01). Notably,
      treatment of bezafibrate caused a marked decrease in the mRNA level (-34%,
      P<0.01) and enzyme activity (-32%, P<0.01) of 11beta-HSD1, whereas the treatment
      substantially augmented the expression (+71%, P<0.01) and secretion (+27%,
      P<0.01) of adiponectin in 3T3-L1 adipocytes. Knockdown of 11beta-HSD1 by siRNA
      confirmed that 11beta-HSD1 acts as a distinct oxoreductase in adipocytes and
      validated the enzyme activity assays in the present study. Effects of bezafibrate
      on regulation of 11beta-HSD1 and adiponectin in murine adipocytes were comparable
      with those in thiazolidinediones. This is the first demonstration that
      bezafibrate directly regulates 11beta-HSD1 and adiponectin in murine adipocytes,
      both of which may contribute to metabolically-beneficial effects by bezafibrate.

PMID- 17190906
TI  - Voltage-gated Ca2+ entry and ryanodine receptor Ca2+-induced Ca2+ release in
      preglomerular arterioles.
AB  - We have previously shown that in afferent arterioles, angiotensin II (ANG II)
      involves activation of the inositol trisphosphate receptor (IP(3)R), activation
      of adenine diphosphoribose (ADPR) cyclase, and amplification of the initial
      IP(3)R-stimulated release of cytosolic Ca(2+) ([Ca(2+)](i)) from the sarcoplasmic
      reticulum (SR) (Fellner SK, Arendshorst WJ. Am J Physiol Renal Physiol 288: F785
      F791, 2004). The response of the ryanodine receptor (RyR) to local increases in
      [Ca(2+)](i) is defined as calcium-induced calcium release (CICR). To investigate
      whether Ca(2+) entry via voltage-gated channels (VGCC) can stimulate CICR, we
      treated fura 2-loaded, freshly isolated afferent arterioles with KCl (40 mM; high
      KCl). In control arterioles, peak [Ca(2+)](i) increased by 165 +/- 10 nM. Locking
      the RyR in the closed position with ryanodine (100 microM) inhibited the
      [Ca(2+)](i) response by 59% (P < 0.01). 8-Br cADPR, a specific blocker of the
      ability of cyclic ADPR (cADPR) to sensitize the RyR to Ca(2+), caused a 43%
      inhibition. We suggest that the lower inhibition by 8-Br cADPR (P = 0.02,
      ryanodine vs. 8-Br cADPR) represents endogenously active ADPR cyclase. Depletion
      of SR Ca(2+) stores by inhibiting the SR Ca(2+)-ATPase with cyclopiazonic acid or
      thapsigargin blocked the [Ca(2+)](i) responses to KCl by 51% (P not significant
      vs. ryanodine or 8-Br cADPR). These data suggest that about half of the increase
      in [Ca(2+)](i) induced by high KCl is accomplished by activation of CICR through
      the ability of entered Ca(2+) to expose the RyR to high local concentrations of
      Ca(2+) and that endogenous cADPR contributes to the process.

PMID- 17190907
TI  - Role of matrix metalloproteinases in renal pathophysiologies.
AB  - Matrix metalloproteinases (MMPs) are a large family of proteinases that remodel
      extracellular matrix (ECM) components and cleave a number of cell surface
      proteins. MMP activity is regulated via a number of mechanisms, including
      inhibition by tissue inhibitors of metalloproteinases (TIMPs). Originally thought
      to cleave only ECM proteins, MMP substrates are now known to include signaling
      molecules (growth factor receptors) and cell adhesion molecules. Recent data
      suggest a role for MMPs in a number of renal pathophysiologies, both acute and
      chronic. This review will focus on the expression and localization of MMPs and
      TIMPs in the kidney, as well as summarizing the current information linking these
      proteins to acute kidney injury, glomerulosclerosis/tubulointerstitial fibrosis,
      chronic allograft nephropathy, diabetic nephropathy, polycystic kidney disease,
      and renal cell carcinoma.

PMID- 17190908
TI  - Parathyroid hormone stimulates endothelial expression of atherosclerotic
      parameters through protein kinase pathways.
AB  - Parathyroid hormone (PTH), the major systemic calcium-regulating hormone, has
      been linked to uremic vascular changes. Considering the possible deleterious
      action of PTH on vascular structures, it seemed logical to evaluate the impact of
      PTH on the receptor of advanced glycation end products (RAGE) and interleukin 6
      (IL-6) mRNA and protein expression, taking into account that such parameters
      might be involved in the pathogenesis of vascular calcification, atherosclerosis,
      and/or arteriolosclerosis. Human umbilical vein cord endothelial cells (HUVEC)
      were stimulated for 24 h with 10(-12)-10(-10) mol/l PTH. The mRNA expression of
      RAGE and IL-6 was established by reverse transcriptase/PCR techniques. RAGE
      protein levels were determined by Western blot and IL-6 secretion was measured by
      ELISA. The pathways by which PTH may have an effect on HUVEC functions were
      evaluated. PTH (10(-11)-10(-10)mol/l) significantly increased RAGE mRNA and
      protein expression. PTH also significantly increased IL-6 mRNA expression without
      changes at protein levels. The addition of protein kinase (PKC or PKA) inhibitors
      or nitric oxide (NO) synthase inhibitors significantly reduced the RAGE and IL-6
      mRNA expression and the RAGE protein expression. PTH stimulates the mRNA
      expressions of RAGE and IL-6 and the protein expression of RAGE. These
      stimulatory effects are probably through PKC and PKA pathways and are also NO
      dependent. Such data may explain the possible impact of PTH on the
      atherosclerotic and arteriosclerotic progression.

PMID- 17190909
TI  - Ex vivo biomechanical properties of the female urethra in a rat model of birth
      trauma.
AB  - Stress urinary incontinence (SUI) is the involuntary release of urine during
      sudden increases in abdominal pressures. SUI is common in women after vaginal
      delivery or pelvic trauma and may alter the biomechanical properties of the
      urethra. Thus we hypothesize that injury due to vaginal distension (VD) decreases
      urethral basal tone and passive stiffness. This study aimed to assess the
      biomechanical properties of the urethra after VD in the baseline state, where
      basal muscle tone and extracellular matrix (ECM) are present, and in the passive
      state, where inactive muscle and ECM are present. Female rat urethras were
      isolated in a rat model of acute SUI induced by simulated birth trauma. Our
      established ex vivo system was utilized, wherein we applied intraluminal static
      pressures ranging from 0 to 20 mmHg. Outer diameter was measured via a laser
      micrometer. Measurements were recorded via computer. Urethral thickness was
      assessed histologically. Stress-strain responses of the urethra were altered by
      VD. Quantification of biomechanical parameters indicated that VD decreased
      baseline stiffness. The passive peak incremental elastic modulus of the distal
      segment in VD urethras was less than for controls (1.84 +/- 0.67 vs. 1.19 +/-
      0.70 x 10(6) dyne/cm(2), respectively; P = 0.016). An increase was noted in
      passive low-pressure compliance values in proximal VD urethras compared with
      controls (9.44 +/- 2.43 vs. 4.62 +/- 0.60 mmHg(-1), respectively; P = 0.04).
      Biomechanical analyses suggest that VD alters urethral basal tone, proximal
      urethral compliance, and distal stiffness. Lack of basal smooth muscle tone, in
      combination with these changes in the proximal and distal urethra, may contribute
      to SUI induced by VD.

PMID- 17190910
TI  - Thiazolidinedione ameliorates renal injury in experimental diabetic rats through
      anti-inflammatory effects mediated by inhibition of NF-kappaB activation.
AB  - Thiazolidinedione (TZD), a ligand for peroxisome proliferator-activated receptor
      gamma (PPAR-gamma), exerts anti-inflammatory effects independently of the insulin
      sensitizing effect. In the present study, we tested the hypothesis that TZD
      prevents the progression of diabetic nephropathy by modulating the inflammatory
      process. Five-week-old Sprague-Dawley rats were divided into three groups: 1)
      nondiabetic control rats (non-DM), 2) diabetic rats (DM), and 3) diabetic rats
      treated with pioglitazone (DM+pio). Diabetes was induced by injection with
      streptozotocin (STZ). The DM+pio group received 0.0002% pioglitazone mixed in
      chow for 8 wk after induction of diabetes. Blood glucose and HbA1c were elevated
      in diabetic rats but did not change by treatment with pioglitazone. Pioglitazone
      reduced urinary albumin excretion and glomerular hypertrophy, suppressed the
      expression of transforming growth factor (TGF)-beta, type IV collagen, and ICAM
      1, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore,
      renal NF-kappaB activity was increased in diabetic rats and reduced by
      pioglitazone. PPAR-gamma was expressed in glomerular endothelial cells in the
      diabetic kidney and in cultured glomerular endothelial cells. High-glucose
      conditions increased the expression of ICAM-1 and the activation of NF-kappaB in
      cultured glomerular endothelial cells. These changes were reduced by
      pioglitazone, ciglitazone, and pyrrolidine dithiocarbamate, an inhibitor of NF
      kappaB. However, pioglitazone did not show the changes in the presence of PPAR
      gamma antagonist GW9662. Our results suggest that the preventive effects of
      pioglitazone may be mediated by its anti-inflammatory actions, including
      inhibition of NF-kappaB activation, ICAM-1 expression, and macrophage
      infiltration in the diabetic kidney.

PMID- 17190911
TI  - Transactivation of the IGF-1R by aldosterone.
AB  - Activation of epithelial sodium channels (ENaC) by aldosterone, insulin, or
      insulin-like growth factor-1 (IGF-1) in renal epithelial cells (including the
      Xenopus laevis renal cell line A6) appears to share some common signaling
      elements subsequent to the initial insulin or IGF-1 receptor activation.
      Previously, the convergence point for insulin or IGF-1 and aldosterone signaling
      was assumed to be downstream of the receptor at the level of phosphatidylinositol
      3-kinase (PI3-K); however, this study shows aldosterone directly transactivates
      the IGF-1 receptor (IGF-1R). In A6 cells, 10-min exposure to aldosterone
      increased the phosphorylation of the IGF-1 receptor, insulin receptor substrate-1
      (IRS-1), and Akt (PKB). Furthermore, aldosterone activated PI3-K and
      phosphorylation of the most downstream element, Akt, was blocked by the specific
      PI3-K inhibitor LY-294002. Transactivation requires aldosterone binding to the
      mineralocorticoid/glucocorticoid receptor and does not require transcription.

PMID- 17190912
TI  - Effects of acute and chronic L-arginine treatment in experimental hyperuricemia.
AB  - Experimental hyperuricemia (HU) results in preglomerular arteriolopathy, cortical
      vasoconstriction, and glomerular hypertension. Recently, uric acid has been shown
      to induce endothelial dysfunction. We therefore studied the effect of acute and
      chronic administration of l-arginine (a substrate for endothelial nitric oxide
      synthase) on the renal hemodynamic and vascular structural alterations induced by
      HU. To induce HU, oxonic acid (OA; 750 mg.kg(-1).day(-1)) was administered in
      male Sprague-Dawley rats. To study the acute effect of arginine, nine rats
      received l-arginine (l-Arg; 15 mg.kg(-1).min(-1)) during micropuncture. To
      elucidate the chronic effect of l-Arg, OA + 1% l-Arg (n = 8) and OA + 2.5% l-Arg
      (n = 6; drinking water) were evaluated throughout the 5-wk period. Eight normal
      control (N), and eight OA, rats were also studied. Kidneys were fixed by
      perfusion and afferent arteriole morphology was evaluated. HU rats developed the
      renal functional and structural alterations described and had suppressed urinary
      excretion of NO(2)(-)/NO(3)(-). Acute stimulation of nitric oxide (NO) synthesis
      markedly increased urinary NO(2)(-)/NO(3)(-), lowered systemic blood pressure,
      and relieved cortical vasoconstriction despite a significant increment of
      glomerular hypertension and afferent arteriole damage. Increasing doses of
      chronic l-Arg were associated with increasing excretion of urinary NO(2)(
      )/NO(3)(-), reduction of systemic hypertension, and prevention of cortical
      vasoconstriction (2.5% l-Arg). In addition, both doses prevented glomerular
      hypertension and preglomerular arteriolopathy. Thus an acute relief of renal
      vasoconstriction in the setting of afferent arteriole damage cannot reverse
      glomerular hypertension, likely due to impairment in preglomerular
      autoregulation. On the other hand, chronic l-Arg preserved arteriolar structures
      probably mediated by the antiproliferative effect of NO on vascular smooth muscle
      cells.

PMID- 17190914
TI  - Optimizing therapy of seizures in patients with brain tumors.
AB  - The mechanism of epilepsy in brain tumor patients is probably multifactorial, and
      its incidence depends on tumor type and location. Refractory epilepsy is common
      in patients with structural brain lesions, and a role for multidrug-resistance
      proteins has been suggested. The medical treatment of epilepsy in brain tumor
      patients has mainly been studied retrospectively, and the optimal management of
      seizures with antiepileptic drugs (AEDs) is unclear. Enzyme-inducing
      anticonvulsants are generally not recommended because they can lead to
      insufficient serum levels of concomitantly administered chemotherapeutic drugs.
      Although valproic acid is an enzyme inhibitor and may therefore lead to toxic
      levels of simultaneously administered chemotherapeutic agents, this does not
      appear to be a major problem in patients with brain tumors. Preliminary
      observations of add-on treatment with the AEDs levetiracetam or gabapentin
      suggest that these non-enzyme-inducing AEDs can be useful for control of seizures
      in patients with brain tumors. Conversely, prophylactic use of AEDs in brain
      tumor patients is generally not recommended.

PMID- 17190913
TI  - Downregulation of the V2 vasopressin receptor in dehydration: mechanisms and role
      of renal prostaglandin synthesis.
AB  - The vasopressin-aquaporin 2 system plays a key role in urine concentration in
      dehydration. In contrast to the upregulation of aquaporin 2, the downregulation
      of the vasopressin V2 receptor in dehydration is known. We investigated the
      mechanisms of this downregulation in dehydration using reverse transcription
      competitive polymerase chain reaction (RT-competitive PCR) and Western blot
      analysis. The incubation of microdissected inner medullary collecting ducts
      (IMCDs) in a hypertonic medium or with vasopressin stimulated V2 receptor mRNA
      and protein expression, showing that dehydration-induced hyperosmolality in renal
      medulla and increased plasma arginine vasopressin (AVP) concentration should
      upregulate V2 receptor. The presence of inhibitory factors on the V2 receptor in
      dehydration was suggested. Prostaglandin E(2) (PGE(2)) is known to inhibit AVP
      induced cAMP production and to increase production in dehydration. PGE(2)
      slightly stimulated V2 receptor mRNA expression in IMCD in vitro. However, PGE(2)
      inhibited V2 receptor mRNA expression in IMCD in the presence of 10(-9) M
      vasopressin. The blockade of PGE(2) synthesis by indomethacin in dehydrated rats
      increased V2 receptor protein expression after 24-48 h with an early increase in
      V2 receptor mRNA expression. In summary, these data suggest that increased
      production of PGE(2) in renal medulla plays a key role in the downregulation of
      V2 receptor in dehydration.

PMID- 17190915
TI  - Optimizing therapy of seizures in neurosurgery.
AB  - The use of antiepileptic drugs (AEDs) in the neurosurgical setting has a number
      of implications, including their possible role in the prevention of seizures
      after acute cerebral insults or brain tumors and the potential for toxicity and
      interactions when these agents are administered in association with radiotherapy
      or chemotherapy. This review discusses these controversial issues and draws the
      following conclusions. 1) AEDs should be prescribed on a short-term basis to
      prevent seizures occurring within the first week after a cerebral insult (trauma,
      neurosurgical procedure) but are ineffective to avoid true post-traumatic
      epilepsy or first seizures in patients with primary or secondary cerebral
      neoplasms. 2) The use of phenytoin and, to a lesser extent, phenobarbital and
      carbamazepine during cranial irradiation is associated with an increased risk for
      severe, potentially fatal, mucocutaneous reactions. In this context, new AEDs
      with a very low potential for allergic cutaneous reactions should be preferred.
      3) Enzyme-inducing AEDs, such as phenytoin, phenobarbital, and carbamazepine, may
      increase the clearance and reduce the clinical efficacy of corticosteroids and
      anticancer agents that are also metabolized by the cytochrome P450 system. The
      newly developed AEDs that are devoid of hepatic metabolism, such as levetiracetam
      and gabapentin, are now recommended because of good results in preliminary
      studies and because they do not show interactions with anticancer agents.

PMID- 17190916
TI  - Optimizing therapy of seizures in patients with HIV and cysticercosis.
AB  - Worldwide, about 40 million people are living with HIV and 50 million people have
      neurocysticercosis (NCC). About 5% of patients with HIV and the majority of
      patients with NCC develop recurrent seizures. Mechanisms of seizure production in
      HIV include mass lesions, meningitis, encephalitis, and ischemia. Seizures in NCC
      may occur at all stages of cyst development, from the vesicular and colloidal to
      the calcified stages. Seizures in HIV present special problems with regard to
      choice of antiepileptic drug (AED) and the potential for drug-drug interactions
      with antiretroviral (ARV) treatments. Newer AEDs with simpler pharmacokinetic
      profiles may be the preferred agents, particularly when protease inhibitors form
      part of ARV regimens. Seizures in NCC are easily controlled with the older AEDs.
      Although there has been some debate about the value of antiparasitic drugs in
      NCC, accumulating data suggest that the use of these agents in active disease
      decreases the risk for development of chronic epilepsy.

PMID- 17190917
TI  - Optimizing therapy of seizures in patients with endocrine disorders.
AB  - Endocrinologic disorders, such as thyroid dysfunction or diabetes, may be
      comorbidities in patients with epilepsy. The choice of medication should address
      such comorbidities wherever possible. Enzyme-inducing antiepileptic drugs (AEDs)
      such as carbamazepine, phenytoin, barbiturates, and oxcarbazepine among the new
      AEDs, may reduce the levels of free and total thyroxin. However, clinically
      relevant thyroid dysfunction owing to AED treatment is rare. Nevertheless, there
      are now better alternative AEDs with similar efficacy to the classic first-line
      drugs but without their enzyme-inducing properties. Such drugs should be
      considered in cases of thyroid dysfunction to reduce the likelihood of iatrogenic
      adverse effects. Sufficient data on some of the new AEDs to support this
      hypothesis are, however, still lacking and urgently needed. Several reports have
      pointed out the possible negative impact of valproate on glucose and insulin
      metabolism and particularly on body weight. The increased risk for development of
      polycystic ovarian syndrome remains a matter of debate but is certainly another
      argument for the development of alternative agents. The group of new AEDs offers
      some potential candidates. Topiramate is the AED that is most likely to lead to
      weight loss; this may be perceived as a positive side effect in some patients.
      This review summarizes the data on the possible impact of AEDs in
      endocrinological disorders, concentrating on thyroid dysfunction, insulin/glucose
      metabolism, and body weight.

PMID- 17190918
TI  - Optimizing therapy of seizures in patients with renal or hepatic dysfunction.
AB  - Patients with epilepsy may suffer from renal or hepatic diseases that interfere
      with their antiepileptic drug (AED) treatment. Furthermore, such diseases may
      themselves cause seizures. Reduced renal function and hypoalbuminemia lead to
      accumulation of renally excreted AEDs, such as gabapentin, vigabatrin,
      topiramate, levetiracetam, and phenytoin. Valproate, lamotrigine, and
      benzodiazepines are less affected. Low protein-bound AEDs are extensively removed
      by hemodialysis and supplemental doses are required for dialysis patients. Uremia
      and related conditions, including intracranial hemorrhage, glucose and
      electrolyte imbalances, and concomitant drug use, can cause seizures, as can
      dialysis encephalopathy, primary cerebral lymphoma, fungal infections, and
      immunosuppressant toxicity in renal transplant recipients. Hepatic dysfunction
      reduces enzymatic metabolism of AEDs and causes hypoalbuminemia. Gabapentin,
      topiramate, and levetiracetam are preferred in these conditions, whereas
      conversely valproate and felbamate are potentially hepatotoxic and should be
      avoided. Seizures related to hepatic encephalopathy are controlled by oral
      lactulose or neomycin. Porphyria sufferers may benefit from gabapentin,
      oxcarbazepine, or levetiracetam. Seizures in Wilson's disease may derive from d
      penicillamine-induced pyridoxine deficiency. Effective treatment of seizures in
      renal and hepatic diseases requires attention to changes in AED pharmacokinetics
      and adequate care of the underlying illnesses. Monitoring of free drug
      concentrations is a valuable aid to therapy.

PMID- 17190919
TI  - Optimizing therapy of seizures in stroke patients.
AB  - Stroke is the leading cause of symptomatic epilepsy in adults, accounting for up
      to one-third of newly diagnosed seizures among the elderly. About 3% to 5% of
      stroke patients will suffer a remote seizure, 54% to 66% of whom will develop
      epilepsy. Thus far, the optimal timing and type of antiepileptic treatment for
      patients with post-stroke seizure and epilepsy have not been specifically
      assessed. Although several studies suggest that seizures alter the functional
      recovery after a stroke, it remains difficult to determine whether or not the
      occurrence of a second seizure in an untreated stroke patient might hamper the
      overall outcome. The decision to initiate antiepileptic drug (AED) treatment
      after a first or a second post-stroke seizure should therefore be individualized,
      primarily based on the functional impact of the first seizure episode and the
      patient's preference. Several converging findings suggest that the majority of
      first-generation AEDs, particularly phenytoin, are not the most appropriate
      choice in stroke patients because of their potential harmful impact on functional
      recovery and bone health, their suboptimal pharmacokinetic profile and
      interaction with anticoagulants or salicylates, their greater likelihood to be
      poorly tolerated, and the lack of level A evidence regarding their specific use
      in elderly patients. Among the new-generation AEDs that do not interact with
      anticoagulants, antiplatelet agents, or bone health, lamotrigine and gabapentine
      are the only two drugs that proved to be more effective than immediate-release
      carbamazepine in elderly patients, providing level A evidence for their use in
      this indication. In addition, gabapentin remains the only drug that has been
      specifically evaluated in stroke patients, demonstrating a high rate of long-term
      seizure freedom. At present, low-dose lamotrigine or gabapentin appears to
      represent the optimal first-line therapy for post-stroke seizure and epilepsy in
      elderly patients or in younger patients requiring anticoagulants. However, low
      dose extended-release carbamazepine might be a reasonable and less expensive
      option in patients with appropriate bone health who do not requiring
      anticoagulation.

PMID- 17190920
TI  - Pharmacologic management of seizures in organ transplant.
AB  - Seizures in a transplant candidate or recipient raise complicated management
      issues, but there are no results from controlled drug trials to guide their
      pharmacologic treatment. Most seizures in the transplant population are isolated
      events that do not require long-term antiseizure therapy. Short-term therapy,
      however, can reduce seizure recurrence. This review focuses on the pharmacologic
      management issues associated with acute and short-term therapy of seizures in
      this population. Phenytoin, fosphenytoin, and phenobarbital are current first
      line therapies. The interactions between immunosuppressants and these
      antiepileptic drugs (AEDs) are of particular importance because the latter may
      reduce immunosuppressant blood levels. Other, newer agents are not subject to
      this interaction, and further studies are needed to define their role in the
      management of seizures in transplant patients.

PMID- 17190921
TI  - Optimizing therapy of seizures in adult patients with psychiatric comorbidity.
AB  - This article provides an overview of appropriate antiepileptic treatment in adult
      patients with chronic epilepsy and concomitant psychiatric disorders. It
      highlights the influence of various treatment options for epilepsy on psychiatric
      symptoms. Six specific topics are discussed: psychosocial aspects and treatment
      compliance; positive and negative psychotropic effects of antiepileptic drugs
      (AEDs); pharmacokinetic and pharmacodynamic interactions between AEDs and
      psychoactive drugs; risks and benefits of resective surgery; the effect of vagal
      nerve stimulation; and recommended strategies for optimizing epilepsy therapy in
      patients with psychiatric disorders. Given the multitude of epilepsy treatment
      options with various CNS effects, it is crucial to select treatments according to
      the clinical profile of each individual patient.

PMID- 17190922
TI  - Seizures and substance abuse: treatment considerations.
AB  - Seizures often occur in substance abusers. The mechanism may be indirect (CNS
      infection, cerebral trauma, stroke, metabolic derangement) or direct
      (intoxication or withdrawal). These mechanisms are not mutually exclusive. A
      patient with obvious overdose or abstinence symptoms might also have meningitis
      or an acute subdural hematoma, and a polydrug abuser might be simultaneously
      intoxicated by one drug while withdrawing from another. Management of such
      patients often requires much more than simple administration of an anticonvulsant
      medication. Medical and surgical emergencies must be identified and nonconvulsive
      signs of intoxication and withdrawal must be addressed. A basic principle in
      treating drug withdrawal is to use an agent from the same pharmacologic class or
      one with a degree of cross-tolerance. Long-term anticonvulsant prophylaxis is
      usually not indicated when drug intoxication or withdrawal is the sole cause of a
      seizure.

PMID- 17190923
TI  - Optimizing therapy of seizures in children and adolescents with ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) can coexist with epilepsy and the
      prevalence of ADHD in epilepsy is three to five times greater than normal. This
      may be an effect of the epilepsy (particularly as a secondary symptom of subtle
      seizures) or of the antiepileptic treatment. There is an ongoing debate about the
      nature of ADHD in epilepsy and especially whether successive comorbidity exists
      (i.e., the possibility that epilepsy lowers the threshold for developing ADHD).
      Treatment of comorbid ADHD may be difficult. Methylphenidate is still the
      treatment of choice for the condition and, although it has been shown that
      neither methylphenidate nor other psychostimulants provoke seizures, there is
      still a possibility that seizure frequency may increase in children with active
      epilepsy.

PMID- 17190924
TI  - Optimizing therapy of seizures in children and adolescents with developmental
      disabilities.
AB  - Children and adolescents with intellectual and developmental disabilities and
      epilepsy are a unique patient population that offers significant challenges. They
      are more likely to suffer lifelong intractable epilepsy with multiple seizure
      types than other patients with epilepsy. In addition, these patients often cannot
      clearly express their complaints about antiepileptic drug (AED) side effects, and
      the caregiver's role becomes all-important as an advocate for the patient.
      Finally, behavioral and psychiatric comorbidities are common and need to be
      considered when choosing an AED in this patient population. Our society will be
      judged by how we care for the most unfortunate among us.

PMID- 17190925
TI  - Optimizing therapy of seizures in women who use oral contraceptives.
AB  - There is no evidence that oral contraceptives (OCs) increase seizure activity,
      and OC use in the setting of antiepileptic drug (AED) treatment provides
      pregnancy prevention at among the highest rates of any available contraceptive
      method. One concern, however, is the increased risk for OC failure with the use
      of cytochrome P450 3A4 enzyme-inducing AEDs, such as phenobarbital,
      carbamazepine, phenytoin, felbamate, topiramate, and oxcarbazepine. Felbamate
      induces metabolism of only the progestogenic component, whereas topiramate
      induces metabolism of only the estrogenic component. There is preliminary
      evidence that lamotrigine induces the metabolism of a progestin, levonorgestrel.
      It is unclear whether the estrogenic or the progestogenic component is more
      clinically important in preventing pregnancy. To ensure maximal pregnancy
      prevention, it is therefore recommended that women taking enzyme-inducing AEDs
      should receive OCs containing at least 50 mug of ethinyl estradiol and that low
      dose formulations in general should not be used. AEDs that do not induce
      cytochrome P450 3A4 enzymes, including valproic acid, gabapentin, levetiracetam,
      tiagabine, vigabatrin, zonisamide, and pregabalin, do not interact with OCs.
      There are no concerns regarding the treatment of seizures or increased pregnancy
      risk with the use of OCs and these non-enzyme-inducing AEDs. Lamotrigine levels,
      however, are reduced by 50% in the setting of OC use. Therefore, women with
      epilepsy taking lamotrigine need to be monitored carefully for seizures when OCs
      are started and for toxicity when OCs are discontinued. Dose adjustment to
      maintain clinical stability may be necessary in these settings. The placebo or
      pill-free week of the OC regimen may also be a period when clinical toxicity can
      occur. Even with the considerations discussed in this review, OCs are a
      reasonable contraceptive option for women with epilepsy taking AEDs.

PMID- 17190926
TI  - Optimizing treatment of epilepsy during pregnancy.
AB  - Freedom from seizures is the ultimate goal in treatment of patients with
      epilepsy. At the same time, the side effects of antiepileptic drugs (AEDs) should
      not outweigh the benefits of treatment. This is particularly important in women
      with epilepsy who wish to become pregnant. These women and their partners should
      be made aware of the risks associated with uncontrolled seizures as well as the
      teratogenicity of some AEDs. Recent studies have indicated a higher risk for
      birth defects and possibly also adverse cognitive effects associated with
      exposure to valproate compared with carbamazepine. Although further studies are
      needed, it appears reasonable to use valproate with caution in women with
      epilepsy who are planning to become pregnant and to consider whether other
      equally effective and safer AEDs are available. However, women who need valproate
      to control their seizures should continue the drug and not be discouraged from
      pregnancy, provided that they receive counseling with the best available
      knowledge. With proper management before conception, during pregnancy, and after
      birth, the vast majority of pregnancies in women with active epilepsy will have a
      favorable outcome.

PMID- 17190927
TI  - Alien hand syndrome.

PMID- 17190928
TI  - Conflicts of interest in expert witnesses: is there a solution?

PMID- 17190929
TI  - Use your imagination: training the brain and not the body to improve chronic pain
      and restore function.

PMID- 17190930
TI  - Childhood-onset temporal lobe epilepsy: neuroimaging predicts seizure control.

PMID- 17190931
TI  - Neurologists for patient safety: where we stand, time to deliver.
AB  - Neurologists have a professional opportunity, an ethical responsibility, and
      sound clinical and economic reasons for engaging in efforts to improve patient
      safety. Better communication with patients and other providers, closer follow-up
      of consultation cases, and more focused supervision of trainees will help to
      reduce current patterns of error and misunderstanding. Patient education with
      attention to health literacy should improve adherence to management plans and
      help to bridge transitions of care across providers and sites. Through teaching
      and by example, neurologists can profoundly influence successive generations of
      clinicians to adopt safer practices, a culture of openness, and enhanced
      professionalism. The federal Safety and Quality Improvement Act of 2005, once
      implemented, should increase the evidence basis for safer care through voluntary,
      legally protected reporting of errors and adverse events within the framework of
      patient safety organizations.

PMID- 17190932
TI  - The impact of litigation on neurologic research.
AB  - Environmental factors likely contribute to the etiology of many progressive
      neurologic diseases. Such factors include putative neurotoxins that are often
      byproducts of commercial industries, potentially exposing corporations to
      liabilities when their products or activities are linked to the development of
      disease. Any hint of scientific data that support such a cause and effect
      relationship often encourages plaintiffs' attorneys to file suits against
      corporations alleging harm to their clients forcing corporations and employers to
      defend themselves. Both plaintiff and defendant teams hire expert witnesses who
      are frequently active investigators in relevant fields to bolster their
      positions. These legal proceedings can influence investigators and hamper
      research. Interactions with researchers can lead to personal financial or career
      gain that may bias research findings or impugn other investigators. Even
      researchers who have not been retained by either side of a legal dispute may be
      forced to respond to subpoenas for research data causing a substantial loss of
      research time for investigators and financial burdens on universities. Courts may
      require release of research records containing personal health information that
      could sully the trust research participants have in investigators. Litigation and
      its peripheral effects may bias investigators, impede research efforts, and harm
      research participants, thereby undermining efforts to understand the cause of
      neurologic disease.

PMID- 17190933
TI  - Active epilepsy as an index of burden of neurocysticercosis in Vellore district,
      India.
AB  - OBJECTIVE: To determine the contribution of neurocysticercosis (NCC) to the
      causation of active epilepsy (AE) in a south Indian community. METHODS: We
      conducted a door-to-door survey of 50,617 people between the ages of 2 and 60
      years in a rural (38,105 people) and urban setting (12,512 people) in the Vellore
      district of the south Indian state of Tamil Nadu to identify patients with AE.
      Patients with AE were investigated with a contrast-enhanced CT scan and serologic
      study using enzyme-linked immunotransfer blot (EITB) for cysticercal antibodies.
      RESULTS: We identified 194 patients with AE. The prevalence of AE was 3.83 per
      1,000 people, with the prevalence in the urban clusters more than twice that in
      the rural clusters (6.23 vs 3.04 per 1,000) (p < 0.0001). A diagnosis of NCC was
      made in 46 (28.4%) of the 162 patients undergoing a CT scan, and EITB was
      positive in 21 (13%) patients. Overall, 55 (34%) patients were diagnosed with NCC
      (11 definitive NCC and 44 probable NCC). There was no significant difference in
      the prevalence of NCC causing AE in the urban (1.28 per 1,000) and rural (1.02
      per 1,000) communities. CONCLUSIONS: NCC is the cause of nearly one-third of all
      cases of AE in both the urban and rural regions. Extrapolating our results to the
      country as a whole leads to an estimated disease burden of 1 million patients in
      India with AE attributable to NCC.

PMID- 17190934
TI  - Intentional motor phantom limb syndrome.
AB  - OBJECTIVE: To investigate the clinical and anatomic correlates of a previously
      unreported form of chronic supernumerary phantom limb, which developed only in
      association with motor intent directed at a hemiplegic-anesthetic upper limb.
      METHODS: We explored the phenomenology of the phantom illusion in the light of
      motor control models. Hemodynamic correlates of supernumerary phantom limb were
      studied with an fMRI sensorimotor paradigm consisting of finger-thumb opposition
      movements. RESULTS: The kinesthetic-proprioceptive illusion of a third arm was
      triggered by any attempt to move the paretic limb, by bimanual actions, and by
      motor imagery involving the nonfunctional limb. The responsible lesion destroyed
      the posterior part of the posterior limb of the internal capsule on the opposite
      side, damaging corticospinal and thalamocortical tracts. Comparison between fMRI
      signals performed during virtual movement of the phantom hand vs imaginary
      movement of the paretic hand showed increased activation in thalamus and caudate
      nucleus in the first condition. CONCLUSIONS: A preserved sense of agency provided
      by intact premotor processes translating intention into action may lead to the
      vivid feeling of movement in a paralyzed limb, similar to kinesthetic illusions
      in amputees. The interruption of thalamic afferences may explain the persistence
      and stability of the phantom by preventing any correction of the mismatch between
      expected and effective movement. The increased blood oxygen level-dependent
      (BOLD) signal in the basal ganglia-thalamus-cortex pathway during movement of the
      supernumerary hand may reflect an abnormal closed-loop functioning of the
      thalamocortical system underlying the phantom phenomenon.

PMID- 17190935
TI  - Anterior choroidal artery aneurysm mimicking cavernous sinus syndrome.

PMID- 17190937
TI  - Recurrent primary thunderclap headache and benign CNS angiopathy: spectra of the
      same disorder?
AB  - OBJECTIVES: To investigate the clinical pictures of patients with recurrent
      thunderclap headaches of unknown etiology and to field-test two relevant
      International Classification of Headache Disorders, 2nd edition (ICHD-II)
      criteria, i.e., primary thunderclap headache (Code 4.6) and benign (or
      reversible) angiopathy of the CNS (Code 6.7.3). METHODS: We prospectively
      recruited patients presenting with idiopathic recurrent thunderclap headaches
      from a hospital-based headache clinic. Detailed histories, neurologic
      examinations, and MRIs and magnetic resonance angiographies (MRAs) were performed
      in all patients to exclude secondary causes. Patients with cerebral
      vasoconstriction received serial MRA follow-up. RESULTS: Fifty-six consecutive
      patients (51 female/5 male, mean age 49.6 +/- 9.8 [range 22 to 76] years) were
      enrolled. Segmental vasoconstriction (or benign CNS angiopathy) was found in 22
      patients (39%). Thunderclap headache recurred in all patients with a median
      frequency of 0.7 times per day for a median period of 14 days (range 6 to 86
      days). The median duration for each single attack was 3 hours. Most patients
      (84%) reported at least one trigger. Nimodipine effectively aborted further
      attacks in 83% of the treated patients. Headache attacks subsided within 3
      months. Four patients (7%) developed ischemic complications. Patients with and
      without vasoconstriction based on MRA images were similar regarding demographics
      and headache profile. Except for the duration criterion, our patients generally
      mapped well into the proposed ICHD-II criteria. CONCLUSIONS: This study suggests
      that the two diagnostic entities proposed by the ICHD-II may present different
      spectra of the same disorder. The distinct headache profile may help physicians
      quickly recognize this disabling headache disorder with risk of stroke and
      provide timely treatment.

PMID- 17190936
TI  - Prevention of menstrual attacks of migraine: a double-blind placebo-controlled
      crossover study.
AB  - OBJECTIVE: To assess the effect of perimenstrual estradiol supplements on
      menstrual attacks of migraine associated with estrogen withdrawal. METHODS: Women
      with regular menstrual cycles and menstrual migraine or menstrually related
      migraine completed an initial three-cycle assessment confirming eligibility for a
      six-cycle crossover study using estradiol or placebo to prevent menstrual attacks
      of migraine. Women collected early morning samples of urine daily for laboratory
      assay and used a fertility monitor to identify peak fertility associated with
      ovulation. Estradiol gel or placebo was first applied on the tenth day following
      the first day of peak fertility and continued daily until, and including, the
      second full day of menstruation. Women kept a daily migraine diary and continued
      their usual treatment for migraine. The main outcome was the number of days
      during gel use on which a migraine occurred. RESULTS: Data from 35 women were
      available for a paired analysis. Percutaneous estradiol was associated with a 22%
      reduction in migraine days (RR 0.78, 95% CI 0.62 to 0.99, p = 0.04); these
      migraines were less severe and less likely to be associated with nausea. This
      was, however, followed by a 40% increase in migraine in the 5 days following
      estradiol vs placebo (RR 1.40, 95% CI 1.03 to 1.92, p = 0.03). CONCLUSION:
      Although perimenstrual percutaneous estradiol showed benefit during treatment,
      this was offset by deferred estrogen withdrawal, triggering post-dosing migraine
      immediately after the gel was stopped. Further work could assess if this could be
      avoided by extending the duration of treatment with estradiol.

PMID- 17190938
TI  - Pulsating enophthalmos in an adult patient with type 1 neurofibromatosis.

PMID- 17190939
TI  - A genotype of exceptional longevity is associated with preservation of cognitive
      function.
AB  - OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV
      homozygosity for I405V) is associated with preservation of cognitive function in
      addition to its association with exceptional longevity. METHODS: We studied
      Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 +/- 0.3 years) for
      the associations of CETP VV genotype and lipoprotein phenotype, using the Mini
      Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort,
      we studied subjects from the Einstein Aging Study (EAS) for associations between
      CETP VV and cognitive impairment. RESULTS: Subjects with MMSE > 25 were twice as
      likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV
      genotype were more likely (61% vs 30%, p = 0.02) to have MMSE > 25. Subjects with
      the VV genotype had lower levels of CETP (1.73 +/- 0.11 vs 2.12 +/- 0.10 mug/mL,
      p = 0.01), higher high-density lipoprotein (HDL) levels (p = 0.02), and larger
      lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold
      increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger
      lipoprotein particle sizes were associated with less dementia and improved
      memory. CONCLUSIONS: Using two independent cohorts, we implicate the longevity
      CETP gene as a modulator of age-related cognitive function. A specific CETP
      genotype is associated with lower CETP levels and a favorable lipoprotein
      profile. It has not been determined whether modulation of this gene prevents age
      related decline or AD.

PMID- 17190940
TI  - Mild cognitive impairment: long-term course of four clinical subtypes.
AB  - OBJECTIVE: To empirically validate the expanded concept of mild cognitive
      impairment (MCI), which differentiates between four clinical subtypes-amnestic
      MCI-single domain, amnestic MCI-multiple domains, nonamnestic MCI-single domain,
      and nonamnestic MCI-multiple domains-and to examine the prevalence, course, and
      outcome of these four clinical MCI subtypes. METHODS: We studied a community
      sample of 980 dementia-free individuals aged 75 years or older who participated
      in the Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants were
      examined by neuropsychological testing based on 6 years of observation. The
      diagnoses of the four clinical MCI subtypes were made according to the original
      and to slightly modified criteria by Petersen et al. (2001) (both with a cutoff
      of 1.0 SD and with a cutoff of 1.5 SD). The complete range of outcome types
      (dementia, death, improvement, stable diagnosis, unstable diagnosis) was
      described for all subtypes. The relative predictive power of stable MCI for
      dementia onset was determined. RESULTS: MCI-single domain is more frequent than
      MCI-multiple domains, and the nonamnestic MCI type is as frequent as the amnestic
      MCI type. The "MCI modified, 1.0 SD" criteria have the highest relative
      predictive power for the development of dementia (sensitivity = 74%, specificity
      = 73%). Alzheimer disease (AD) was the most common type of dementia at follow-up
      in all but one MCI subtype. Participants with nonamnestic MCI-multiple domains
      were more likely to progress to a non-AD dementia. CONCLUSIONS: It has been
      assumed that each MCI subtype is associated with an increased risk for a
      particular type of dementia. We can only partially agree with this.

PMID- 17190941
TI  - Minocycline-induced skin and dental pigmentations.

PMID- 17190942
TI  - Social-economic costs and quality of life of Alzheimer disease in the Canary
      Islands, Spain.
AB  - OBJECTIVES: To examine the economic burden (direct and indirect costs) of
      Alzheimer disease (AD) and to analyze the impact on health-related quality of
      life (HRQOL) for patients with AD and caregivers in 2001 in the Canary Islands,
      Spain. METHODS: Two hundred thirty-seven patients (61% of those contacted) were
      recruited from the Alzheimer's Disease Association in the Canary Islands.
      Demographic, health resources utilization, informal care, indirect costs, and
      quality of life data were collected from primary caregivers of patients as proxy
      respondents. HRQOL was measured for patients and caregivers with the generic
      questionnaire EQ-5D. RESULTS: The average annual cost per patient with AD was
      28,198 (36,144 US dollars). The most important categories of costs were for
      informal care and drugs. Costs increased with cognitive impairment with an
      average annual cost of 14,956 (19,171 US dollars) for mild, 25,562 (32,765 US
      dollars) for moderate, and 41,669 (53,411 US dollars) for severe patients. The
      total cost of patients with AD in Canary Islands was 259 (332 US dollars)
      million. The HRQOL with the EQ-5D social tariff was 0.29 for patients and 0.67
      for caregivers. The EQ-5D VAS (thermometer) score was 42 for patients and 62 for
      caregivers. CONCLUSIONS: Direct health care costs of AD represented 2.4% of the
      total public health care expenditure in the Canary Islands. Across all severity
      levels, we estimated a total annual cost of 10 (13 US dollars) billion for AD
      patients older than 65 years in Spain. The degree of severity of the patients
      with AD substantially influenced the quality of life of the patients but not that
      of the caregivers.

PMID- 17190944
TI  - Measuring brain stem and cerebellar damage in parkinsonian syndromes using
      diffusion tensor MRI.
AB  - OBJECTIVE: To use diffusion tensor MRI to quantify and compare degeneration of
      the pons and cerebellar peduncles in multiple system atrophy (MSA), progressive
      supranuclear palsy (PSP), and Parkinson disease (PD) and to relate changes in
      diffusion measures to clinical features and localized atrophy. METHODS: We used a
      region-of-interest approach to measure changes in fractional anisotropy and mean
      diffusivity in the middle cerebellar peduncles, decussation of the superior
      cerebellar peduncles, and pons in 17 patients with MSA, 17 with PSP, 12 with PD,
      and 12 healthy volunteers. We also evaluated atrophy of the cerebellar peduncles
      and pons on T2-weighted magnetic resonance images in patients with MSA and PSP.
      RESULTS: In MSA, fractional anisotropy was markedly reduced in the middle
      cerebellar peduncles, and mean diffusivity increased both here and in the pons
      compared with other groups, whereas in PSP, mean diffusivity was strikingly
      increased in the decussation of superior cerebellar peduncles. Cerebellar ataxia
      was related to mean diffusivity in the middle cerebellar peduncles (r = 0.71, p =
      0.001) and pons (r = 0.60, p = 0.01) in MSA. Diffusion measures were related to
      localized atrophy in both MSA and PSP. CONCLUSIONS: Diffusion tensor MRI can be
      used to quantify neurodegenerative processes in different brain stem and
      cerebellar structures in multiple system atrophy and progressive supranuclear
      palsy during life, and may have diagnostic value. Larger studies of early,
      undifferentiated parkinsonian syndromes are indicated to provide estimates of the
      relative diagnostic value of diffusion measures, atrophy measures, and visual
      assessment of scans.

PMID- 17190943
TI  - Extent and distribution of white matter hyperintensities in normal aging, MCI,
      and AD.
AB  - OBJECTIVE: To analyze the extent and spatial distribution of white matter
      hyperintensities (WMH) in brain regions from cognitively normal older individuals
      (CN) and patients with mild cognitive impairment (MCI) and Alzheimer disease
      (AD). METHODS: We studied 26 mild AD, 28 MCI, and 33 CN. MRI analysis included
      quantification of WMH volume, nonlinear mapping onto a common anatomic image, and
      spatial localization of each WMH voxel to create an anatomically precise
      frequency distribution map. Areas of greatest frequency of WMH from the WMH
      composite map were used to identify 10 anatomic regions involving periventricular
      areas and the corpus callosum (CC) for group comparisons. RESULTS: Total WMH
      volumes were associated with age, extent of concurrent vascular risk factors, and
      diagnosis. After correcting for age, total WMH volumes remained significantly
      associated with diagnosis and extent of vascular risk. Regional WMH analyses
      revealed significant differences in WMH across regions that also differed
      significantly according to diagnosis. In post-hoc analyses, significant
      differences were seen between CN and AD in posterior periventricular regions and
      the splenium of the CC. MCI subjects had intermediate values at all regions.
      Repeated measures analysis including vascular risk factors in the model found a
      significant relationship between periventricular WMH and vascular risk that
      differed by region, but regional differences according to diagnosis remained
      significant and there was no interaction between diagnosis and vascular risk.
      CONCLUSIONS: Differences in white matter hyperintensities (WMH) associated with
      increasing cognitive impairment appear related to both extent and spatial
      location. Multiple regression analysis of regional WMH, vascular risk factors,
      and diagnosis suggest that these spatial differences may result from the additive
      effects of vascular and degenerative injury. Posterior periventricular and corpus
      callosum extension of WMH associated with mild cognitive impairment and Alzheimer
      disease indicate involvement of strategic white matter bundles that may
      contribute to the cognitive deficits seen with these syndromes.

PMID- 17190945
TI  - Herbicide exposure modifies GSTP1 haplotype association to Parkinson onset age:
      the GenePD Study.
AB  - BACKGROUND: Polymorphisms in the glutathione S-transferase pi gene (GSTP1),
      encoding GSTP1-1, a detoxification enzyme, may increase the risk of Parkinson
      disease (PD) with exposure to pesticides. Using the GenePD Study sample of
      familial PD cases, we explored whether GSTP1 polymorphisms were associated with
      the age at onset of PD symptoms and whether that relation was modified by
      exposure to herbicides. METHODS: Seven single-nucleotide polymorphisms (SNPs)
      were genotyped and tested for association with PD onset age in men in three
      strata: no exposure to herbicides, residential exposure to herbicides, and
      occupational exposure to herbicides. Haplotypes were similarly evaluated in
      stratified analyses. RESULTS: Three SNPs were associated with PD onset age in the
      group of men occupationally exposed to herbicides. Three additional SNPs had
      significant trends for the association of PD onset age across the herbicide
      exposure groups. Haplotype results also provided evidence that the relation
      between GSTP1 and onset age is modified by herbicide exposure. One haplotype was
      associated with an approximately 8-years-earlier onset in the occupationally
      exposed group and a 2.8-years-later onset in the nonexposed group. CONCLUSIONS:
      Herbicide exposure may be an effect modifier of the relation between glutathione
      S-transferase pi gene polymorphisms and onset age in familial PD.

PMID- 17190946
TI  - Detection of CSF 14-3-3 protein in Guillain-Barre syndrome.
AB  - OBJECTIVE: To search for biologic markers in the Guillain-Barre syndrome (GBS),
      we studied CSF samples from patients with GBS and neuropathy of various
      etiologies for the presence of 14-3-3 protein. METHODS: CSF samples from patients
      with GBS, chronic neuropathies, motor neuron disease (MND), definite sporadic
      Creutzfeldt-Jakob disease (sCJD), and normal control subjects were analyzed by
      standard immunoblot assay, using a polyclonal anti-14-3-3 antibody. CSF samples
      were also tested with antibodies recognizing specific isoforms of 14-3-3
      proteins, either after one-dimensional or two-dimensional electrophoretic
      separation. RESULTS: A positive 14-3-3 assay was observed in 29 of 38 patients
      with GBS and in 4 patients with MND and other neuropathies, including 2 subjects
      with vasculitic neuropathy (VN). In GBS, 14-3-3 protein was detected as early as
      12 to 48 hours after disease onset and showed an isoform pattern different from
      that encountered in patients with noninflammatory neuropathies, VN, MND, and
      sCJD. Immunohistochemical studies performed in archival fatal GBS cases disclosed
      marked 14-3-3 expression by mononuclear inflammatory infiltrates and Schwann
      cells. CONCLUSION: CSF 14-3-3 assay may represent a useful biologic marker in
      patients with Guillain-Barre syndrome.

PMID- 17190947
TI  - Muscle imaging in dominant core myopathies linked or unlinked to the ryanodine
      receptor 1 gene.
AB  - OBJECTIVE: To characterize the muscle involvement of patients with central core
      disease (CCD) caused by mutations in the ryanodine receptor 1 gene (RYR1) and to
      compare these findings with those from patients with core myopathies unlinked to
      the RYR1 gene. METHODS: We performed a systematic muscular imaging assessment in
      11 patients with an RYR1 gene mutation and compared these findings with those of
      5 patients from two unrelated families with autosomal dominant core myopathies
      not linked to RYR1, ACTA1, or MYH7 gene loci. RESULTS: All patients with RYR1 CCD
      had a characteristic pattern with predominant involvement of the gluteus maximus,
      adductor magnus, sartorius, vastus intermediolateralis, soleus, and lateral
      gastrocnemius muscles. In contrast, muscle CT in the first family not linked to
      RYR1 showed predominant affection of the gluteus minimus and hamstring muscles,
      whereas the second family presented with predominant involvement of the gluteus
      minimus, vastus intermediolateralis, tibialis anterior, and medial gastrocnemius
      muscles. In addition to muscle imaging data, we present detailed information on
      the clinical and pathologic findings of these novel phenotypes of core myopathies
      not linked to RYR1. CONCLUSIONS: Our data suggest genetic heterogeneity in
      autosomal dominant core myopathies and the existence of additional unidentified
      genes.

PMID- 17190948
TI  - Heart rate changes are insensitive for detecting postasphyxial seizures in
      neonates.
AB  - We studied heart rate (HR) changes during 169 seizures (mean 12 per patient,
      range 8 to 18) in 14 neonates with severe birth asphyxia. HR changes were found
      in 21 seizures (12.4%) in eight patients (HR increases in four, decreases in one,
      and both patterns in three patients), suggesting the existence of neonatal
      cerebral hemispheric connections with brainstem autonomic regulatory centers. HR
      monitoring appears to be insensitive for detecting postasphyxial neonatal
      seizures.

PMID- 17190949
TI  - Severe myoclonic epilepsy of infancy (Dravet syndrome): recognition and diagnosis
      in adults.
AB  - Establishing an etiologic diagnosis in adults with refractory epilepsy and
      intellectual disability is challenging. We analyzed the phenotype of 14 adults
      with severe myoclonic epilepsy of infancy. This phenotype comprised heterogeneous
      seizure types with nocturnal generalized tonic-clonic seizures predominating,
      mild to severe intellectual disability, and variable motor abnormalities. The
      diagnosis was suggested by a characteristic evolution of clinical findings in the
      first years of life. Ten had mutations in SCN1A and one in GABRG2.

PMID- 17190950
TI  - Treatment of the first tonic-clonic seizure does not affect long-term remission
      of epilepsy.
AB  - We followed 419 patients with a first, unprovoked, primarily or secondarily
      generalized tonic-clonic seizure, randomized to immediate antiepileptic treatment
      or to treatment only in the event of seizure recurrence. The probability of
      achieving a 2-year remission was 72 vs 57% at 3 months, 84 to 79% at 3 years, and
      85 to 86% at 10 years (p = NS). The probability of entering 5-year remission was
      47 to 40, 58 to 58, and 64 to 64% (p = NS). Early treatment does not affect the
      long-term prognosis of epilepsy.

PMID- 17190951
TI  - CDIP-58 can measure the impact of botulinum toxin treatment in cervical dystonia.
AB  - We compared the responsiveness of the Cervical Dystonia Impact Profile (CDIP-58),
      Medical Outcome Study Short Form-Health Survey (SF-36), Functional Disability
      Questionnaire (FDQ), and Pain and Activities of Daily Living subscales of the
      Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in participants with
      cervical dystonia treated with botulinum toxin A. Subscales of CDIP-58 were more
      sensitive in detecting statistical and clinical change than comparable subscales
      of the SF-36, FDQ, and TWSTRS.

PMID- 17190952
TI  - Clinico-immunologic aspects of botulinum toxin type B treatment of cervical
      dystonia.
AB  - In this multicenter study of 100 patients with cervical dystonia, we examined the
      immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical
      response with the presence of blocking antibodies (Abs) using a novel mouse
      protection assay. One-third of the patients who were negative for BTX-B Abs at
      baseline became positive for BTX-B Abs at last visit. Thus, the high antigenicity
      of BTX-B limits its long-term efficacy.

PMID- 17190953
TI  - Reduced cardiac 123I-MIBG scintigraphy in idiopathic REM sleep behavior disorder.
AB  - Idiopathic REM sleep behavior disorder (RBD) may represent prodromal
      synucleinopathies. We report markedly reduced cardiac (123)I
      metaiodobenzylguanidine uptake, consistent with the loss of sympathetic
      terminals, in idiopathic RBD. We also demonstrate that this reduction is of the
      same magnitude as that found in patients with Parkinson disease. The results are
      consistent with the hypothesis that idiopathic RBD in older patients is a forme
      fruste of Lewy body disease.

PMID- 17190954
TI  - A founder haplotype for autosomal dominant sensory ataxia in Eastern Canada.
AB  - We present phenotypic and genotypic data for an additional family with autosomal
      dominant sensory ataxia, a disease characterized by gait difficulties associated
      with diminished sensation in the limbs and areflexia. The same disease haplotype
      spanning the entire SNAX1 locus is observed in affected members of this second
      family, enabling the locus to be reduced to a 7.3-cM interval.

PMID- 17190955
TI  - Dihydropteridine reductase deficiency: levodopa's long-term effectiveness without
      dyskinesia.
AB  - We report an adult patient lacking endogenous synthesis of monoamines (dopamine,
      serotonin, and catecholamines) due to a severe dihydropteridine reductase (DHPR)
      deficiency. With levodopa and 5-hydroxytryptophan (5HTP) supplementation, the
      patient exhibited moderate mental retardation, acute episodes of parkinsonism,
      and episodes of depression. Despite the use of levodopa from age 3 months, he
      exhibited no dyskinesia or dopaminergic cell loss as suggested by normal PET
      imaging of the dopamine transporter.

PMID- 17190956
TI  - fMRI reveals novel functional neuroanatomy in a child with perinatal stroke.
AB  - Children who have experienced a perinatal stroke often develop normal language
      function, but the neurobiologic mechanisms underlying this plasticity remain
      unclear. In this study, we used fMRI to compare, at two ages, the functional
      neuroanatomy of a child with perinatal stroke with that of age-appropriate
      cohorts of typically developing children. Although the data for this child are
      similar to the control group, there are age-dependent differences.

PMID- 17190957
TI  - CNS involvement in hereditary neuropathy with pressure palsies (HNPP).
AB  - We assessed seven patients with hereditary neuropathy with liability to pressure
      palsies (HNPP) with 16 electrophysiological tests and cranial MRI for CNS
      abnormalities. Mean latencies differed between patients with HNPP and controls
      for the blink reflex, the jaw-opening reflex, and acoustic evoked potentials. MRI
      abnormalities were observed in four patients. Our study suggests subclinical but
      functionally relevant CNS myelin damage in HNPP.

PMID- 17190959
TI  - Carotid artery dissection and middle cerebral artery stroke following
      methamphetamine use.

PMID- 17190958
TI  - Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced
      neuropathy.
AB  - We conducted a randomized, open-label, controlled trial to assess the efficacy of
      oxcarbazepine for prophylaxis against oxaliplatin-induced peripheral neuropathy
      (OxIN). Thirty-two patients with colon cancer received 12 courses of the FOLFOX-4
      regimen and were randomly assigned to receive oxcarbazepine (600 mg BID) or
      chemotherapy without oxcarbazepine. The incidence of OxIN was strikingly
      decreased in patients receiving oxcarbazepine (31.2% vs 75%). Oxcarbazepine may
      prevent OxIN symptoms. Further larger placebo-controlled trials are warranted to
      confirm our results.

PMID- 17190960
TI  - An acute, life-threatening, hypersensitivity reaction to riluzole.

PMID- 17190961
TI  - ALS in a patient with hereditary neuropathy with liability to pressure palsy.

PMID- 17190962
TI  - Ptosis as a feature of late-onset glycogenosis type II.

PMID- 17190963
TI  - Unusual features in a boy with the rapsyn N88K mutation.

PMID- 17190964
TI  - A randomized study of two interferon-beta treatments in relapsing-remitting
      multiple sclerosis.

PMID- 17190965
TI  - Does the arousal system contribute to near death experience?

PMID- 17190966
TI  - Practice parameter: diagnosis and prognosis of new onset Parkinson disease (an
      evidence-based review): report of the Quality Standards Subcommittee of the
      American Academy of Neurology.

PMID- 17190967
TI  - Function and connectivity in human primary auditory cortex: a combined fMRI and
      DTI study at 3 Tesla.
AB  - Human primary auditory cortex (PAC) is functionally organized in a tonotopic
      manner. Past studies have used neuroimaging to characterize tonotopic
      organization in PAC and found similar organization as that described in mammals.
      In contrast to what is known about PAC in primates and nonprimates, in humans,
      the structural connectivity within PAC has not been defined. In this study,
      stroboscopic event-related functional magnetic resonance imaging (fMRI) was
      utilized to reveal mirror symmetric tonotopic organization consisting of a high
      low-high frequency gradient in PAC. Furthermore, diffusion tensor tractography
      and probabilistic mapping was used to study projection patterns within tonotopic
      areas. Based on earlier physiological and histological work in nonhuman PAC, we
      hypothesized the existence of cross-field isofrequency (homotopic) and within
      field non-isofrequency (heterotopic)-specific axonal projections in human PAC.
      The presence of both projections types was found in all subjects. Specifically,
      the number of diffusion tensor imaging (DTI) reconstructed fibers projecting
      between high- and low-frequency regions was greater than those fibers projecting
      between 2 high-frequency areas, the latter of which are located in distinct
      auditory fields. The fMRI and DTI results indicate that functional and structural
      properties within early stages of the auditory processing stream are preserved
      across multiple mammalian species at distinct evolutionary levels.

PMID- 17190968
TI  - Oscillatory activity in human parietal and occipital cortex shows hemispheric
      lateralization and memory effects in a delayed double-step saccade task.
AB  - We applied magnetoencephalography (MEG) to record oscillatory brain activity from
      human subjects engaged in planning a double-step saccade. In the experiments,
      subjects (n = 8) remembered the locations of 2 sequentially flashed targets (each
      followed by a 2-s delay), presented in either the left or right visual hemifield,
      and then made saccades to the 2 locations in sequence. We examined changes in
      spectral power in relation to target location (left or right) and memory load
      (one or two targets), excluding error trials based on concurrent eye tracking.
      During the delay period following the first target, power in the alpha (8-12 Hz)
      and beta (13-25 Hz) bands was significantly suppressed in the hemisphere
      contralateral to the target. When the second target was presented, there was a
      further suppression in the alpha- and beta-band power over both hemispheres. In
      this period, the same sensors also showed contralateral power enhancements in the
      gamma band (60-90 Hz), most significantly prior to the initiation of the
      saccades. Adaptive spatial filtering techniques localized the neural sources of
      the directionally selective power changes in parieto-occipital areas. These
      results provide further support for a topographic organization for delayed
      saccades in human parietal and occipital cortex.

PMID- 17190969
TI  - Effective connectivity within the distributed cortical network for face
      perception.
AB  - Face perception elicits activation within a distributed cortical network in the
      human brain. The network includes visual ("core") regions, as well as limbic and
      prefrontal ("extended") regions, which process invariant facial features and
      changeable aspects of faces, respectively. We used functional Magnetic Resonance
      Imaging and Dynamic Causal Modeling to investigate effective connectivity and
      functional organization between and within the core and the extended systems. We
      predicted a ventral rather than dorsal connection between the core and the
      extended systems during face viewing and tested whether valence and fame would
      alter functional coupling within the network. We found that the core system is
      hierarchically organized in a predominantly feed-forward fashion, and that the
      fusiform gyrus (FG) exerts the dominant influence on the extended system.
      Moreover, emotional faces increased the coupling between the FG and the amygdala,
      whereas famous faces increased the coupling between the FG and the orbitofrontal
      cortex. Our results demonstrate content-specific dynamic alterations in the
      functional coupling between visual-limbic and visual-prefrontal face-responsive
      pathways.

PMID- 17190970
TI  - Event frequency modulates the processing of daily life activities in human medial
      prefrontal cortex.
AB  - Event sequence knowledge is necessary to learn, plan, and perform activities of
      daily life. Clinical observations suggest that the prefrontal cortex (PFC) is
      crucial for goal-directed behavior such as carrying out plans, controlling a
      course of actions, or organizing everyday life routines. Functional neuroimaging
      studies provide further evidence that the PFC is involved in processing event
      sequence knowledge, with the medial PFC (Brodmann area 10) primarily engaged in
      mediating predictable event sequences. However, the exact role of the medial PFC
      in processing event sequence knowledge depending on the frequency of
      corresponding daily life activities remains obscure. We used event-related
      functional magnetic resonance imaging while healthy volunteers judged whether
      event sequences from high- (HF), moderate- (MF), and low-frequency (LF) daily
      life activities were correctly ordered. The results demonstrated that different
      medial PFC subregions were activated depending on frequency. The anterior medial
      Area 10 was differentially activated for LF and the posterior medial Area 10 for
      HF activities. We conclude that subregions of the medial PFC are differentially
      engaged in processing event sequence knowledge depending on how often the
      activity was reportedly performed in daily life.

PMID- 17190971
TI  - Toll-like receptors are part of the innate immune defense system of sponges
      (demospongiae: Porifera).
AB  - During evolution and with the emergence of multicellular animals, the need arose
      to ward off foreign organisms that threaten the integrity of the animal body.
      Among many different receptors that participate in the recognition of microbial
      invaders, toll-like receptors (TLRs) play an essential role in mediating the
      innate immune response. After binding distinct microbial components, TLRs
      activate intracellular signaling cascades that result in an induced expression of
      diverse antimicrobial molecules. Because sponges (phylum Porifera) are filter
      feeders, they are abundantly exposed to microorganisms that represent a potential
      threat. Here, we describe the identification, cloning, and deduced protein
      sequence from 3 major elements of the poriferan innate response (to bacterial
      lipopeptides): the TLR, the IL-1 receptor-associated kinase-4-like protein (IRAK
      4l), and a novel effector caspase from the demosponge Suberites domuncula. Each
      molecule shares significant sequence similarity with its homologues in higher
      Metazoa. Sequence homologies were found in particular within the family-specific
      domains toll/interleukin-1 receptor/resistance (TLR family), Ser/Thr/Tyr kinase
      domain (IRAK family), and CASc (caspase family). In addition, in situ
      hybridization and immunohistological analyses revealed an abundance of SDTLR
      (TLR) transcripts in epithelial layers of the sponge surface (exopinacoderm and
      endopinacoderm). Furthermore, it is shown that both SDTLR and SDIRAK-4 like
      (IRAK) are expressed constitutively, regardless of treatment with synthetic
      triacyl lipopeptide Pam(3)Cys-Ser-(Lys)(4). In contrast, SDCASL (caspase)
      expression is highly Pam(3)Cys-Ser-(Lys)(4) inducible. However, blocking of the
      lipopeptide with recombinant TLR prior to its application completely prevented
      the induced expression of this poriferan caspase. These results underscore that
      the phylogenetically oldest extant metazoan phylum is provided already with the
      signaling pathways of the antimicrobial host-defense system of Metazoa.

PMID- 17190972
TI  - Perspectives: the possible influence of assisted reproductive technologies on
      transgenerational reproductive effects of environmental endocrine disruptors.
AB  - Demasculinization by environmental endocrine-disrupting chemicals (EDCs) is
      observed in many animal species but less evident in humans. Rodent studies with
      gestational exposure to either the fungicide vinclozolin or the insecticide
      methoxychlor demonstrate impaired male fertility with abnormal DNA methylation
      patterns in spermatozoa. Once established, these epigenetic changes may be
      permanent and thus paternally passed to subsequent generations. Conclusive
      evidence of a similar phenomenon in humans has not been established, but several
      observations bring up the possibility. Some, but not all, studies show an
      increase in male genital abnormalities after prenatal EDC exposure. Other studies
      demonstrate sperm abnormalities in males with EDC contact, although it is unclear
      as to whether this is due to prenatal or postnatal exposure. Although not
      examined in males with EDC exposure, one study shows gamete DNA methylation
      abnormalities in males with severe oligospermia. A subsequent study failed to
      corroborate these findings. The use of assisted reproductive techniques including
      intracytoplasmic sperm injection has removed natural selection barriers thus
      enabling reproduction in males that would otherwise be sterile. This review
      explores the hypothesis that prenatal EDC exposure results in transgenerational
      male reproductive abnormalities propagated by the use of assisted reproductive
      technologies.

PMID- 17190973
TI  - Long-lasting reductions of ethanol drinking, enhanced ethanol-induced sedation,
      and decreased c-fos expression in the Edinger-Westphal nucleus in Wistar rats
      exposed to the organophosphate chlorpyrifos.
AB  - Intermittent or continuous exposure to a wide variety of chemically unrelated
      environmental pollutants might result in the development of multiple chemical
      intolerance and increased sensitivity to drugs of abuse. Interestingly, clinical
      evidence suggests that exposure to organophosphates might be linked to increased
      ethanol sensitivity and reduced voluntary consumption of ethanol-containing
      beverages in humans. The growing body of clinical and experimental evidence
      emerging in this new scientific field that bridges environmental health sciences,
      toxicology, and drug research calls for well-controlled studies aimed to analyze
      the nature of the neurobiological interactions of drugs and pollutants. Present
      study specifically evaluated neurobiological and behavioral responses to ethanol
      in Wistar rats that were previously exposed to the pesticide organophosphate
      chlorpyrifos (CPF). In agreement with clinical data, animals pretreated with a
      single injection of CPF showed long-lasting ethanol avoidance that was not
      secondary to altered gustatory processing or enhancement of the aversive
      properties of ethanol. Furthermore, CPF pretreatment increased ethanol-induced
      sedation without altering blood ethanol levels. An immunocytochemical assay
      revealed reduced c-fos expression in the Edinger-Westphal nucleus following CPF
      treatment, a critical brain area that has been implicated in ethanol intake and
      sedation. We hypothesize that CPF might modulate cellular mechanisms (decreased
      intracellular cAMP signaling, alpha-7-nicotinic receptors, and/or cerebral
      acetylcholinesterase inhibition) in neuronal pathways critically involved in
      neurobiological responses to ethanol.

PMID- 17190974
TI  - Gestational exposure to nonylphenol causes precocious mammary gland development
      in female rat offspring.
AB  - This study examined whether or not exposure to 4-nonylphenol (NP) during late
      gestation affects reproductive and mammary development in the offspring of female
      rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg),
      atrazine (ATR, 100 mg/kg), or corn oil on gestation days 15-19. The uterus
      weights of the NP (100 mg/kg/d)-exposed pups were higher than those of the
      controls but the weights of the other organs were unchanged. Delayed mammary
      gland (MG) development was detected in the ATR pups on PND 4 and persisted
      through to PND 66. The high dose NP pups had advanced lobular development of
      their MG on PND 22, while the glands from the low dose NP pups were no different
      morphologically from the controls. Immunohistochemical comparisons of the mammary
      sections from PND 41 demonstrated low levels of estrogen receptor (ER) staining
      in the control gland stroma and epithelium but higher levels in the tissue of the
      pups exposed to NP and ATR. ATR also elevated ER in the stroma surrounding the
      epithelial layer of the terminal end buds. The level of progesterone receptor
      (PR) staining was markedly lower in the epithelium of the 100 mg/kg NP glands vs.
      the control glands. However, PR was present at high levels in the epithelium of
      the 10 mg/kg NP glands and was even more prominent in the ATR-exposed ductal
      epithelium and fat cell nuclei. The level of prolactin staining was only elevated
      in glands containing lobule areas (NP-exposed) compared with the control levels.
      These results suggest that NP and ATR have opposite effects on the development of
      MG after gestational exposure. Exposure to them during the critical period of
      epithelial outgrowth altered the receptor levels of mammary progesterone and
      prolactin and might contribute to the differences in the mammary morphology at
      PND 41.

PMID- 17190975
TI  - Articular chondrocyte culturing for cell-based cartilage repair: needs and
      perspectives.
AB  - Articular cartilage displays a limited capacity of self-regeneration after
      injury. Thus, the biology of this tissue and its cellular components - the
      chondrocytes - has become the focus of several investigations, driven by tissue
      engineering and the basic and clinical research fields, aiming to ameliorate the
      present clinical approaches to cartilage repair. In this work, we present a brief
      recapitulation of the events that lead to cartilage development during the
      skeletal embryonal growth. The intrinsic phenotypic plasticity of the mesenchymal
      precursors and the adult chondrocytes is evaluated, dependent on the cell source,
      its physiopathological state, and as a function of the donor's age. The
      phenotypic changes induced by the basic culturing techniques are also taken into
      account, thus highlighting the phenotypic plasticity of the chondrocyte as the
      main property which could couple the differentiation process to the repair
      process. Chondrocyte proliferation and the contemporary maintenance of the
      chondrogenic differentiation potential are regarded as the two primary goals to
      be achieved in order to fulfill the quantitative needs of the clinical
      applications and the qualitative requirements of a properly repaired tissue. In
      this light, the effects of several growth factors and medium supplements are
      investigated. Finally, the latest improvements in culturing conditions and their
      possible clinical applications are presented as well.

PMID- 17190976
TI  - Differentiation status of human renal proximal and distal tubular epithelial
      cells in vitro: Differential expression of characteristic markers.
AB  - BACKGROUND: The culture of human renal tubular cells of well-defined nephron
      origin is an important basis in the research of various physiological and
      pathophysiological mechanisms in the kidney. In vitro differentiation of cultured
      cells is affected by cell isolation and culture conditions. Our study describes
      in vitro differentiation of cultured human renal proximal and distal (thick
      ascending limb and early distal) tubular epithelial cells. METHODS: Proximal
      tubular cells (PTC) and early distal tubular cells (DTC) were isolated
      immunomagnetically and cultured. In vitro differentiation was assessed by Western
      blot analysis and reverse transcriptase polymerase chain reaction using
      characteristic markers. Morphologic characterization was shown by fluorescence
      and scanning electron microscopy. RESULTS: E-cadherin was highly expressed in
      DTC, whereas expression was low in PTC. In contrast to DTC, in PTC, intercellular
      adhesion molecule 1 and aquaporin 1 were constitutively expressed at high levels.
      Both cell types expressed cytokeratin 18 and Na-K-ATPase but not alpha-smooth
      muscle actin. Morphological analysis showed that PTC develop long microvilli,
      whereas DTC formed short microvilli in culture, and both express the tight
      junction protein zona occludens protein 1. CONCLUSIONS: We demonstrate
      differential expression of E-cadherin, intercellular adhesion molecule 1 and
      aquaporin 1 in cultured PTC and DTC as described for the renal tubule in vivo. We
      could show the in vitro differentiation of the cells, and thus, their usefulness
      as an in vitro model of the human proximal and early distal tubule.

PMID- 17190977
TI  - Morphometric assessment of the impact of serum thymulin immunoneutralization on
      pituitary cell populations in peripubertal mice.
AB  - Thymulin is a thymic hormone involved in several aspects of intra- and
      extrathymic T-cell differentiation. Thymulin also possesses hypophysiotropic
      activity which suggests that this metallopeptide may play an important role in
      thymus-pituitary communication, particularly during early life. The aim of the
      present study was to evaluate the impact of serum thymulin suppression from birth
      to peripuberty on the morphology of different pituitary cell populations in
      prepubertal C57Bl/6 mice. Animals were submitted to immunoneutralization of
      circulating thymulin from postnatal day 1 to the end of the study (age 32 days).
      From their 1st day of life, the animals were submitted to a protocol of
      intraperitoneal injections of rabbit anti-thymulin serum (alpha-FTS) and normal
      rabbit serum (NRS) in the controls. On their 33rd day of life, the animals were
      killed and their pituitaries were immediately dissected, fixed and immunostained
      using the EnVision system with primary antibodies against growth hormone,
      thyrotropin, corticotropin, gonadotropins and prolactin. Morphometry was
      performed by means of an image analysis system. The following parameters were
      calculated: volume density = Sigma cell area/reference area (RA); cell density
      (CD) = number of cells/RA, and cell size (expressed in microm2). Serum thymulin
      was measured by a rosette bioassay while pituitary hormones were assayed by
      radioimmunoassay. Serum prolactin, luteinizing hormone, follicle-stimulating
      hormone, growth hormone and thyroid-stimulating hormone were significantly lower
      in the alpha-FTS animals of either sex compared with the corresponding NRS
      counterparts. The somatotrope, lactotrope and corticotrope populations showed a
      significant decrease in CD, while cell hypertrophy was observed in some of the
      pituitary cell populations of the alpha-FTS group compared to the NRS group. In
      the alpha-FTS group, there were sex differences in the morphometric changes
      observed. Our results suggest that serum thymulin plays a significant role during
      early life in the postnatal maturation of endocrine cells of the mouse anterior
      pituitary gland.

PMID- 17190978
TI  - Chemical coding of submucosal type V neurons in porcine ileum.
AB  - In this study, we attempted to determine the proportion of type V neurons
      relative to the putative whole neuron population in the two submucosal plexuses
      of pigs identified by their neurofilament immunoreactivity. The total neuron
      number was estimated in cuprolinic blue (CB)/anti-Hu protein (HU) costained
      wholemounts as the sum of the number of CB+/HU+, CB+/HU- and CB-/HU+ neurons. In
      the external submucosal plexus (ESP), HU labelled 98.6% and CB 97.3% of neurons.
      In the internal submucosal plexus, HU labelled 98.3%, whereas CB only marked
      92.5% of neurons. Furthermore, we investigated the chemical coding of submucosal
      type V neurons and searched for submucosal, non-type V neurons displaying the
      same chemical coding as the myenteric type V neurons described earlier, i.e. the
      colocalization of calcitonin gene-related peptide (CGRP) and somatostatin (SOM).
      In order to facilitate immunohistochemical detection of neuroactive peptides,
      ileal segments were pretreated with colchicine prior to fixation. Type V neurons
      in the ESP occurred either as single cells displaying one or few prominent
      dendrite(s) or within aggregates displaying a dendritic tangle. In this plexus,
      type V neurons amounted to between 0.9 and 1.6% of all CB-stained neurons. ESP
      type V neurons displayed immunoreactivities for choline acetyl transferase
      (95.8%) and leucine-enkephalin (73.9%). All type V neurons were negative for
      neuronal nitric oxide synthase. Fifty-eight percent of ESP CGRP/SOM co
      immunoreactive neurons displayed type V morphology, whereas 42% were non-type V
      neurons. Thus, the chemical coding of ESP type V neurons is in principal similar
      to that of the myenteric type V neurons described earlier. In the internal
      submucosal plexus, we found no type V neurons. In this plexus, 0.2% of all
      neurons counterstained with HU displayed CGRP/SOM coreactivity. As had been
      observed earlier concerning the myenteric type V neurons, ESP type V neurons were
      also closely apposed by conspicuous accumulations of boutons reactive for the
      same markers as the neurons themselves. Although we cannot exclude that axons of
      CGRP/SOM-reactive enteric, non-type V or extrinsic neurons end synaptically on
      type V neurons, we suggest that the main synaptic input to type V neurons
      originates from other type V neurons. This presents an argument for an
      interneuronal role of type V neurons.

PMID- 17190980
TI  - Primary spinal primitive neuroectodermal tumor: case series and review of the
      literature.
AB  - Primary spinal primitive neuroectodermal tumor (PSPNET) is extremely rare and
      only 25 cases have been reported in the world literature so far. Three patients
      of 8, 9 and 18 years of age, who presented with variable grades of neurological
      deficit were diagnosed as having a dorsal intramedullary lesion, a holocord
      lesion and cervical extradural tumor with extraspinal extension, respectively,
      and were operated at our institute. The histopathology of all 3 children revealed
      PNET. The clinical course, image characteristics and outcome of the 3 children
      are described, and the relevant literature is reviewed. The following conclusions
      were drawn from the present study and review of the literature. PNET may manifest
      itself as a primary lesion of the spine unlike the more common drop metastases
      from an intracranial lesion. PSPNET may be intramedullary, intradural and
      extradural with variable extraspinal extension. PSPNET may present as holocord
      intramedullary lesion, an entity which has not been described earlier. These
      lesions have a short history, significant neurological deficits and rapid course
      of illness. PSPNET, though an established entity, did not find a place in the WHO
      2000 classification of CNS tumors. Hence its status has to be defined.

PMID- 17190979
TI  - Leg muscles differ in spatial activation patterns with differing levels of
      voluntary plantarflexion activity in humans.
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate the differential
      activity between and within individual muscles commonly grouped as
      plantarflexors. Much of the previous information gathered on plantarflexor
      activity has been attained using electromyographic recordings. In this study, we
      used magnetic resonance imaging which allowed us to look at spatial differences
      in activation. METHODS: Twenty-two human subjects exercised under four different
      conditions - combinations of loads of 25 or 65% of maximum voluntary contraction
      (MVC) and the direction of plantarflexion at a sagittal and off-sagittal angle.
      Before and after each exercise condition, T2-weighted magnetic resonance images
      were collected. Regions of interest were drawn around the lateral gastrocnemius
      (LG), medial gastrocnemius (MG), soleus (SOL), peroneus longus (PER) and tibialis
      anterior (TA) muscles and analyzed for differences. RESULTS: Significant
      increases in T2 relaxation times during 25% MVC conditions were found for PER
      and, during the 65% MVC, for all four muscles considered plantarflexors (LG, MG,
      SOL, PER). No significant differences were found between sagittal and off
      sagittal conditions. Within LG and MG, greater increases in T2 times with
      exercise were found in proximal regions compared with distal regions. CONCLUSION:
      These results are consistent with suggestions that individual members of muscle
      groups are capable of differential activity and that for at least some muscles,
      such differential activity may exist within subvolumes of individual muscles.

PMID- 17190981
TI  - Outcome of meningomyelocele/lipomeningomyelocele in children of northern India.
AB  - OBJECTIVE: To evaluate the clinical profile, associated anomalies and surgical
      outcome of children with meningomyelocele (MMC)/lipomeningomyelocele. METHODS:
      Out of a total of 181 cases of spinal dysraphism treated at our Institute between
      1996 and 2004, 102 (56.35%) cases of MMC/lipomeningomyelocele were analyzed
      retrospectively and prospectively. The clinical profile and radiological findings
      of these children were recorded. Craniospinal MRI was the essential investigation
      and was done as a management protocol at our Institute for these children. Eighty
      two out of 102 (80.3%) cases had pure MMC/lipomeningomyelocele and 20/102 (19.6%)
      had associated split cord malformation (SCM; complex spina bifida). All these
      children underwent surgery for their primary and associated malformations as
      indicated. They were clinically assessed over a mean follow-up period of 3.6
      years ranging from 1.5 months to 8 years. No urodynamic or evoked potential
      studies were done to assess the sphincteric outcome following surgery. RESULTS:
      Forty-six (45.1%) of children with MMC had other associated tethering lesions,
      including the presence of SCM. Craniospinal axis screening remained an important
      tool to understand the associated tethering lesions and malformations. Only 58.8%
      of children had hydrocephalus; thus the incidence was much lower compared with
      reports from the western literature (80-96%). 63.3% of children with overt
      hydrocephalus required shunt surgery prior to the definitive surgery; however,
      23.3% of cases required a shunt after the MMC has been closed. Improvement in
      clinical profile following microneurosurgery was observed in 42.8% of cases with
      motor involvement, 46.8% of cases with sensory dysfunction and 39.5% of cases
      with sphincteric involvement. Motor improvement was seen in 43.6% of cases of
      pure MMC/lipomeningomyelocele as compared to only 40.0% of cases of complex spina
      bifida. Sensory improvement was also better in pure MMC/lipomeningomyelocele
      group being seen in 48.0% of cases as compared to only 42.9% of cases of complex
      spina bifida. CONCLUSION: Presence of SCM with MMC is referred to as complex
      spina bifida and is seen in a significant proportion (19.6%) of all cases of MMC.
      Thorough assessment of the craniospinal imaging needs to be done to look for the
      presence of multiple tethering lesions which could be present in the same case.
      Not all children with spinal dysraphism with hydrocephalus required shunt surgery
      or CSF diversion but a constant and vigilant follow up could avoid it in 13.3% of
      cases. Improvement in motor and sensory dysfunction was better in the pure
      MMC/lipomeningomyelocele group than in the complex spina bifida group.
      Improvement in sphincteric dysfunction, although seen in significant cases, was
      less compared with improvement in motor and sensory dysfunction. This probably
      represents a lack of definitive objective criteria for urodynamic improvement and
      a lack of proper rehabilitation. Electromyographic studies and uroflowmetry are
      required to asses the true sphincteric outcome following surgery.

PMID- 17190982
TI  - Syringomyelia in infants secondary to mobile congenital atlantoaxial dislocation.
AB  - We report a characteristic pattern of 'waist-like' syringomyelia observed in
      three infants having mobile and reducible congenital atlantoaxial dislocation.
      The syringomyelia in at least two of these cases was diagnosed to be an
      intramedullary tumor. Following atlantoaxial fixation, all three patients had
      long-term recovery of their symptoms.

PMID- 17190983
TI  - Correction of sagittal craniosynostosis using a novel parietal bone fixation
      technique: results over a 10-year period.
AB  - Isolated sagittal synostosis is a common form of craniosynostosis affecting
      roughly 1 in 5,000 children at birth. This results in a scaphocephalic head shape
      with a characteristically elongated anterior-posterior dimension and narrowed
      biparietal diameter. We present our experience with the correction of
      scaphocephaly due to sagittal synostosis using cranial vault reconstruction with
      a novel form of parietal bone fixation in 21 patients over 10 years. The medial
      fixation results in a hinging effect whereby transverse brain growth at the
      squamoid suture is enhanced. This results in excellent cosmetic results that are
      immediate and durable without the need for postoperative molding helmets.
      Furthermore, the complications associated with this procedure are limited.

PMID- 17190984
TI  - Chronic subdural hematoma of the neonate: report of two cases and literature
      review.
AB  - We report the cases of 2 infants who were born with macrocephaly and bulging
      fontanelles and were subsequently found to have chronic subdural hematomas on
      imaging studies. The etiology of 1 infant was likely due to an inherent
      coagulopathy, while no etiology could be found for the other. The subdural
      hematomas were managed by craniotomy in 1 infant and serial subdural taps in the
      other. There are currently only 8 other case reports of chronic subdural hematoma
      of the neonate in the literature. Our cases and a brief review of the literature
      are presented.

PMID- 17190985
TI  - MR demonstration of complete cerebellar and corpus callosum agenesis.
AB  - Complete cerebellar agenesis is a very rare entity, which occurs during the early
      period of embryogenesis and is usually associated with severe motor dysfunction.
      We report a case of complete cerebellar agenesis with complete corpus callosum
      agenesis diagnosed on magnetic resonance imaging (MRI). These anomalies were also
      associated with rudimentary pons.

PMID- 17190986
TI  - Transient sixth nerve palsies and torticollis secondary to parietal arteriovenous
      malformation.
AB  - Arteriovenous malformations (AVMs) can compress on any intracranial structures,
      and the presence and nature of ophthalmologic symptoms and signs depend on the
      size and location of the AVMs. We report an 11-month-old girl with parietal
      fistulous AVM, transient bilateral sixth nerve palsies and torticollis. The
      postoperative period was uneventful and she was discharged in a good condition.
      The patient recovered from transient bilateral abducens nerve palsies and
      torticollis; she was asymptomatic during the 18-month follow-up period.

PMID- 17190987
TI  - Radiation-induced meningioma following prophylactic radiotherapy for acute
      lymphoblastic leukemia in childhood.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common childhood
      malignancy. Although it was considered to be a poor prognostic disease, modern
      treatment protocols (aggressive chemotherapy and prophylactic cranial
      irradiation) have resulted in dramatically improved survival rates. In a group of
      low-risk ALL patients, the 5-year survival rate is estimated to be 85%. However,
      ALL patients who undergo this treatment are at risk of developing secondary
      neoplasms related to treatment, which has become an increasingly recognized
      problem. CASE DESCRIPTION: A 3-year-old boy with ALL was successfully treated
      with chemotherapy (vincristine, prednisolone, mercaptopurine and methotrexate)
      and prophylactic cranial irradiation (total 18 Gy). At the age of 23, he was
      admitted to our hospital for weakness in the right leg. Computed tomography and
      magnetic resonance imaging revealed a parasagittal tumor of the left
      frontoparietal lobe with perifocal edema. The tumor was completely removed
      surgically and pathohistologically diagnosed as atypical meningioma. CONCLUSION:
      Long-term survivors who received radiotherapy for ALL in childhood are at risk
      for late complications, including radiation-induced meningioma. Therefore,
      careful follow-up neurological examinations, for example magnetic resonance
      imaging, are indicated in these patients. In addition, late complications should
      be taken into account during the initial planning of prophylactic radiotheraphy
      dosage, which has implications for informed consent of the patient.

PMID- 17190989
TI  - Pentasomy 49,XXXXY associated with a Chiari type 1 malformation and cervical
      syrinx.
AB  - Pentasomy 49,XXXXY occurs in 1/85,000 newborn males. The origin of this
      particular form of aneuploidy is believed to be a result of consecutive
      nondisjunction events during maternal meiosis. Typical presentation consists of
      hypotonia, developmental delay, various dysmorphic features, and severe
      hypogenitalism. A 13-year-old with pentasomy 49,XXXXY and a Chiari type 1
      malformation with an associated cervical syrinx is presented.

PMID- 17190988
TI  - Endoscopic third ventriculostomy in prepontine-suprasellar tuberculoma with
      tuberculous meningitis hydrocephalus: a case report.
AB  - We present a case of prepontine-suprasellar tuberculoma involving the
      premamillary region of the third ventricular floor, a site suitable to perform an
      endoscopic third ventriculostomy (ETV) stoma, managed endoscopically, and discuss
      our findings. A 5-year-old male child was admitted in an unconscious state with a
      history of gradually progressive symptoms of raised intracranial pressure and low
      grade fever for the last 3 months. Head computed tomography showed thick
      enhancing basal exudates, a prepontine-suprasellar ring-enhancing lesion with
      consequent obstructive hydrocephalus. The child was subjected to urgent endoscopy
      which revealed multiple ependymal tubercles along with prepontine-suprasellar
      tuberculoma involving the premamillary region of the third ventricular floor. The
      tuberculoma was decompressed using a 5-french catheter, and ETV was performed.
      Postoperatively, the child improved clinicoradiologically on antitubercular
      chemotherapy and needed no further cerebrospinal fluid diversion surgery; he is
      under regular follow-up. We conclude that ETV may be attempted even in the
      presence of thick basal exudates and/or prepontine-suprasellar tuberculoma.

PMID- 17190990
TI  - Unusual presentation of cervical spinal intramedullary arachnoid cyst in
      childhood: case report and review of the literature.
AB  - The authors report a 7-year-old girl who presented with progressive quadriparesis
      which had started a month before admission. Magnetic resonance imaging of the
      spine revealed an intramedullary cystic lesion extending from C(2) to C(4). After
      performing a C(2-5) laminectomy, the cyst was drained and anatomically
      fenestrated with the subarachnoid space by a 1-cm vertical median myelotomy
      without using a stent. The histopathological findings revealed arachnoid cyst. In
      the first month after operation, the neurological deficits disappeared gradually,
      except for a slight left upper paresis. Cervical spinal intramedullary arachnoid
      cyst is extremely rare and should be considered in the differential diagnosis of
      intramedullary cystic lesions in childhood. Recovery is possible after subtotal
      excision and fenestration of the cyst to allow communication with the
      subarachnoid space even if neurological deficits are present for a long time.

PMID- 17190991
TI  - Moyamoya disease associated with midaortic syndrome.
AB  - We report a 1-year-old girl who presented moyamoya disease associated with
      midaortic syndrome. She had been treated for cardiac failure and severe
      hypertension due to midaortic syndrome until she suffered seizure and repeated
      cerebral ischemic attack. Cerebral angiography revealed stenosis of the bilateral
      internal carotid artery at its terminal portion. She was successfully treated
      with encephaloduroarteriosynangiosis, and ischemic attack ceased postoperatively.
      This is the first report of moyamoya disease with midaortic syndrome. Although
      cerebral ischemic attack has been effectively managed by
      encephaloduroarteriosynangiosis, renovascular hypertension is still difficult to
      control.

PMID- 17190993
TI  - Occipital mega encephalocele associated with acute inflammation.

PMID- 17190992
TI  - Dumbbell-shaped paraganglioma of the cervical spine in a child.
AB  - Paragangliomas are tumors arising from extra-adrenal paraganglia and account for
      0.3% of all neoplasms. The carotid body and temporal bone are the most frequent
      sites of paraganglioma, though it has been reported to occur in almost every part
      of the body. Spinal paragangliomas are uncommon and mainly take the form of
      intradural compression of the cauda equina or thoracic cord. Extradural
      paragangliomas are still rare; only few cases involving the dorsolumbar spine
      have been reported. We are reporting an interesting case of a dumbbell-shaped
      primary extradural paraganglioma of the cervical spine in an 8-year-old boy that
      presented with progressively increasing spastic quadriparesis.

PMID- 17190994
TI  - Total ossification of choroid plexus papilloma mimicking calcified petrous bone
      pathology.

PMID- 17190995
TI  - Atretic parietal cephalocele.

PMID- 17190996
TI  - Ventricular CSF drainage and medulloblastoma.

PMID- 17190997
TI  - Delayed-onset craniosynostosis.

PMID- 17190998
TI  - Clinical genetics for the pulmonologist: introduction.

PMID- 17190999
TI  - Genetic predisposition to asthma and atopy.
AB  - A large number of studies have tried to identify heritable components in the
      susceptibility to asthma and atopy phenotypes. This review examines the evidence
      of multigenetic inheritance for these conditions. We identified in the literature
      at least 372 gene-disease association studies for asthma and 124 for atopy
      published in the last 6 years. Gene-environment analyses were performed in 41 and
      14 articles, respectively, in the same time period. Many postulated associations
      have been probed with limited sample sizes and will require more extensive
      replication and large-scale evidence. Meta-analyses have been performed for
      polymorphisms in 5 genes and provide modest evidence for genetic association of
      asthma with ADAM33 and TNFA gene polymorphisms. Meta-analyses of linkage studies
      show that it is unlikely to detect strong linkage peaks for asthma
      susceptibility. However, linkage was claimed between loci on chromosomes 2, 4, 6,
      9, 10, 11 and 15 and total serum IgE levels. Careful definitions and
      standardization of phenotypes across teams of investigators are important to
      endorse. New large-scale testing platforms may offer new opportunities for
      discovering susceptibility gene variants, but they need to be coupled with
      careful study design, international collaboration, and possibly also dissection
      of gene-environment interactions.

PMID- 17191000
TI  - Out of breath, asleep at the wheel.

PMID- 17191001
TI  - Vascular endothelial growth factor and sleep apnea: clutching at straws in the
      night.

PMID- 17191002
TI  - Adrenergic influence on the permeability of sheep diaphragmatic parietal pleura.

PMID- 17191003
TI  - Reply to 'Dieulafoy's disease of the lung: a potential disaster for the
      bronchoscopist'.

PMID- 17191004
TI  - Detection by flow cytometry of ESAT-6- and PPD-specific circulating CD4+ T
      lymphocytes as a diagnostic tool for tuberculosis.
AB  - BACKGROUND: The identification of mycobacteria represents the gold standard in
      the diagnosis of tuberculosis (TB), but it is not applicable in all patients, and
      immunological tests, such as the tuberculin skin test (TST), are not specific and
      sensitive enough. METHODS: By flow cytometry, we measured the CD4 T-cell response
      to purified protein derivative (PPD) and early secretory antigenic target-6 (ESAT
      6) protein using the intracellular cytokine staining technique on whole blood
      samples obtained from active TB (n = 16), latent TB (n = 17), Bacille Calmette
      Guerin (BCG)-vaccinated (n = 11) and healthy (n = 10) donors. All the patients
      were also tested with conventional TST. RESULTS: The identification by flow
      cytometry of PPD-specific T lymphocytes upon antigen stimulation of whole blood
      enables the discrimination of active TB, latent TB and BCG-vaccinated subjects
      from healthy individuals, whereas the ESAT-6 response discriminated active TB
      from healthy and BCG-vaccinated individuals. Moreover, this test enables
      identification of active TB patients who were negative on TST and to distinguish
      between TB and non-typical mycobacteria TB infections. CONCLUSIONS: The
      identification by flow cytometry of antigen-specific T lymphocytes upon antigen
      stimulation of whole blood has a better positive predictive value than TST, and
      could represent a further tool in the diagnosis of TB infection.

PMID- 17191006
TI  - Effects of triterpenoid-rich extracts of Ganoderma tsugae on airway
      hyperreactivity and Th2 responses in vivo.
AB  - BACKGROUND: Airway inflammation and Th2 responses play central roles in allergic
      asthma. We have previously reported that Ganoderma tsugae supplementation could
      attenuate airway inflammation in the murine model. Since it remains unclear which
      part of the G. tsugae exerts this effect on allergic asthma in vivo, this study
      was meant to investigate if triterpenoid extracts have anti-inflammatory effects
      on airway responses and regulatory effects on Th2 responses. METHODS: BALB/c mice
      sensitized intraperitoneally and challenged with ovalbumin (OVA) were treated
      with either triterpenoid-rich extracts (TRE) of G. tsugae or prednisolone for 2
      weeks. The effects of TRE on bronchial airway hyperresponsiveness (AHR), airway
      inflammation, serum antigen-specific antibody levels, and cytokine secretions
      from splenocytes were evaluated. RESULTS: TRE supplementation significantly
      decreased AHR and reduced the total infiltrating leukocytes and eosinophils, as
      well as the levels of inflammatory mediators, such as interleukin (IL)-4, IL-5
      and eotaxin in bronchoalveolar lavage fluid when compared with those of the
      control group. Lung histology also showed less cell recruitment and lung damage.
      TRE supplements suppressed IL-5 secretions from OVA-stimulated splenocytes, but
      did not affect the cell number of splenocytes, which was also reduced by
      prednisolone. Although OVA-specific immunoglobulin E levels were not
      significantly different among the groups, a lower level of OVA-specific
      immunoglobulin G1, another Th2-related antibody, was found in TRE and
      prednisolone treatment. CONCLUSIONS: TRE of G. tsugae exert anti-inflammatory
      effects on airway responses and attenuate Th2 responses without the overall
      immunosuppression effects in allergic murine models of asthma.

PMID- 17191005
TI  - Oral sensitization to peanut is highly enhanced by application of peanut extracts
      to intact skin, but is prevented when CpG and cholera toxin are added.
AB  - BACKGROUND: CpG oligonucleotides might offer an alternative to conventional
      immunotherapy in preventing and potentially reversing Th2-biased immune
      deregulation which leads to allergy. However, non-invasive ways of
      administration, especially in peanut-allergic patients, should be explored.
      METHODS: One hundred micrograms of whole peanut protein extract (PE) alone, or
      mixed with cholera toxin (CT, 50 microg) plus CpG (100 microg) as adjuvant, was
      applied on intact skin of mice (40 min, twice). Initiation of an immune response
      was monitored by detection of specific antibodies in sera. The effect of this
      pretreatment on a further oral sensitization by PE was then evaluated by assaying
      antibodies and cytokines specific for PE and purified allergens. Cytokine
      production in liver 40 min after skin application was also assayed. RESULTS: Two
      brief skin applications of PE alone highly potentiated further oral
      sensitization, as demonstrated by very intense specific IgE, IL-4 and IL-5
      productions. Conversely, skin pretreatment with PE and CT + CpG efficiently
      prevented further sensitization via gastro-intestinal exposure. In both cases,
      the specificity of the antibodies and cytokines was the same as in control mice.
      CT + CpG treatment allowed the rapid production of IL-12 and TGFbeta in liver and
      of specific IgG2a in sera, suggesting the activation of Th1 and/or regulatory T
      cells. CONCLUSIONS: Oral sensitization to peanut is highly enhanced by a previous
      short exposure of allergens to intact skin. Conversely, the use of CT + CpG
      adjuvant for skin application efficiently prevents further oral sensitization.
      The potential of such treatment in specific immunotherapy needs to be evaluated.

PMID- 17191007
TI  - Osteoimmunology.
AB  - Osteoimmunology is an interdisciplinary research field combining the exciting
      fields of osteology and immunology. An observation that contributed enormously to
      the emergence of osteoimmunology was the accelerated bone loss caused by
      inflammatory diseases such as rheumatoid arthritis. Receptor activator of nuclear
      factor kappaB ligand (RANKL), which is the main regulator of osteoclastogenesis,
      was found to be the primary culprit responsible for the enhanced activation of
      osteoclasts: activated T cells directly and indirectly increased the expression
      of RANKL, and thereby promoted osteoclastic activity. Excessive bone loss is not
      only present in inflammatory diseases but also in autoimmune diseases and cancer.
      Furthermore, there is accumulating evidence that the very prevalent skeletal
      disorder osteoporosis is associated with alterations in the immune system.
      Meanwhile, numerous connections have been discovered in osteoimmunology beyond
      merely the actions of RANKL. These include the importance of osteoblasts in the
      maintenance of the hematopoietic stem cell niche and in lymphocyte development as
      well as the functions of immune cells participating in osteoblast and osteoclast
      development. Furthermore, research is being done investigating cytokines,
      chemokines, transcription factors and co-stimulatory molecules which are shared
      by both systems. Research in osteoimmunology promises the discovery of new
      strategies and the development of innovative therapeutics to cure or alleviate
      bone loss in inflammatory and autoimmune diseases as well as in osteoporosis.
      This review gives an introduction to bone remodeling and the cells governing that
      process and summarizes the most recent discoveries in the interdisciplinary field
      of osteoimmunology. Furthermore, an alternative large animal model will be
      discussed and the pathophysiological alterations of the immune system in
      osteoporosis will be highlighted.

PMID- 17191008
TI  - Effect of sulodexide on albuminuria, NAG excretion and glomerular filtration
      response to dopamine in diabetic patients.
AB  - BACKGROUND: Albuminuria is the best and most readily available marker for
      glomerular damage and progressive renal function loss in patients with diabetic
      nephropathy. Recently, administration of the oral glycosaminoglycan sulodexide (a
      mixture of 80% fast-moving heparin and 20% dermatan sulphate) was shown to
      effectively decrease albumin excretion rate in diabetics with nephropathy. AIMS:
      To evaluate whether the hypoalbuminuric effect of sulodexide is associated with
      improvement of the renal vascular or tubule function. METHODS: Forty-five type 1
      diabetic patients, affected by diabetic nephropathy with albuminuria for at least
      5 years, were randomly allocated to sulodexide or untreated. Those allocated to
      sulodexide were given 100 mg of sulodexide daily for 120 days. Renal vascular
      function (DIR) and N-acetyl-beta-D-glucosaminidase (NAG) excretion were estimated
      before and at the end of the study, the former in thesulodexide group only. DIR
      was measured as two Cr(cl) lasting 120 min (before and during 2 mug/kg b.w. i.v.
      dopamine). RESULTS: The analysis of trends during the study demonstrated a marked
      reduction of albuminuria in the sulodexide group (from 126.1 +/- 15.41 to 93.6 +/
      13.7 mg/day). DIR rose from 13.2 +/- 2.1% to 15.44 +/- 1.9% (relative increase:
      +16.9%), and NAG excretion showed a decreasing trend decreased in the sulodexide
      group only (from 5.1 +/- 0.62 to 4.7 +/- 0.40 U/g(creat)). CONCLUSION: The
      findings presented in this study indicate for the first time that orally
      available sulodexide may favorably affect the renal vascular function in type 1
      diabetic patients with nephropathy and microalbuminuria. The effect of sulodexide
      on NAG is strongly influenced by the baseline NAG values, with a significant NAG
      reduction in the patients with the highest baseline NAG values.

PMID- 17191009
TI  - HIV infection among Uganda women with cervical cancer: a retrospective study.
AB  - OBJECTIVE: To assess whether there is an association between HIV and invasive
      cervical cancer (ICC). METHODOLOGY: A case-control study was conducted in Kampala
      between 1993 and 1995. 116 women with ICC were matched by age and parity with 116
      hospital controls. Participants were tested for HIV and interviewed to assess
      risk factors for ICC and HIV. The association between HIV and ICC was assessed by
      conditional logistic regression. RESULTS: HIV prevalence was 18% among cases and
      15% among controls. The odds of having ICC for HIV-infected patients was 1.27
      (95% CI 0.58-2.80) when compared to controls, and the odds of being infected with
      HIV was higher in ICC patients aged <33 years (OR = 3.81) when compared to
      controls of similar age. HIV-infected ICC patients were younger (mean age 35.8
      years) compared to 46.5 years in the ICC HIV-negative group (p = 0.021).
      CONCLUSION: HIV is associated with an earlier onset of ICC.

PMID- 17191010
TI  - Fractal analysis of the maternal surface of the placenta: preliminary report.
AB  - AIMS: The objective of this study was to determine whether the maternal surface
      of the placenta is fractal, and whether the mean fractal dimension differs
      according to the gestational age and clinically or pathologically different
      conditions. METHODS: Using digitized images of the maternal surface of 75
      placentas, fractal dimensions were measured with a fractal analysis software.
      RESULTS: The mean fractal dimension of the maternal surface of the placentas
      significantly exceeded the topological dimension of a surface (= 2). This means
      that the morphological pattern of the maternal surface fulfills the mathematical
      definition of fractal structures. Among the three different groups of gestational
      age, the mean fractal dimension in 22-29 weeks was significantly lower than that
      in 30-36 and 37-41 weeks (p = 0.022 and 0.014, respectively). Although not
      significantly different (p = 0.149), in 30-36 weeks the mean fractal dimension of
      the placentas complicated by pregnancy-induced hypertension (PIH) was greater
      than that without PIH. CONCLUSION: Fractal geometry, a vocabulary of irregular
      shapes, can be useful for describing quantitatively the architecture of the
      maternal surface of the placenta and become a useful tool for analyzing
      physiological and pathological placental formation mathematically.

PMID- 17191011
TI  - Prevalence and antimicrobial resistance patterns of Aeromonas strains isolated
      from drinking water samples in istanbul, Turkey.
AB  - The aim of this study was to determine the prevalence and the resistance patterns
      of Aeromonas spp. in drinking water in Istanbul, Turkey. We investigated a total
      of 1,680 drinking water samples (840 tap water and 840 domestic water tank
      samples) for Aeromonas strains between June 2002 and October 2005. A total of 147
      Aeromonas strains were isolated from 49 (6%) of 840 tap water samples and from 98
      (12%) of 840 domestic water tank samples. Antibiotic susceptibility of Aeromonas
      strains was determined by the disc diffusion method, according to the CLSI
      (Clinical Laboratory Standards Institute) recommendation. Among the 147 Aeromonas
      strains, the prevalence was: A. hydrophila 68 (46%), A. sobria 50 (34%), A.
      caviae 11 (8%), A. salmonicida 9 (6%), A. veronii 5 (3%) and A. jandaei 4 (3%).
      Approximately 55% of the strains were resistant to ampicillin, 48% to
      erythromycin, 41% to amoxicillin-clavulanic acid, 28% to ceftazidime, 27% to
      cefoxitin, 26% to ceftriaxone and cefotaxime, 22% to piperacillin, 14% to
      trimethoprim-sulfamethoxazole, 12% to tetracycline, 11% to aztreonam, 8% to
      meropenem, 6% to imipenem, 2% to nalidixic acid, 1% to ciprofloxacin, tobramycin
      and gentamicin. None of the strains were resistant to amikacin and netilmicin. In
      conclusion, Aeromonas spp. isolated from drinking water in Istanbul have a
      resistance potential and the antibiotic resistance rates of A. hydrophila, A.
      sobria and A. caviae were usually higher than those of other Aeromonas strains.
      It should be kept in mind that these microorganisms in drinking water might be a
      potential risk for public health.

PMID- 17191013
TI  - Effects of ectodomain sequences between HR1 and HR2 of F1 protein on the specific
      membrane fusion in paramyxoviruses.
AB  - OBJECTIVES: To explore the effects of ectodomain sequences between HR1 and HR2 of
      F1 protein on the specific interaction with its homologous hemagglutinin
      neuraminidase (HN) in paramyxoviruses. METHODS: Site-directed mutagenesis was
      used to obtain mutants containing new enzyme sites on the F genes of Newcastle
      disease virus (NDV) and human parainfluenza virus (hPIV), and four DNA segments
      located between the HR1 and HR2 (NDV F-1, hPIV F-1, NDV F-2 and hPIV F-2) were
      obtained by cutting mutant F genes with specific endonucleases. Gene
      recombination was used to get chimeric F proteins NDV-C1 and hPIV-C1 by
      exchanging NDV F-1 and hPIV F-1 each other, and NDV-C2 and hPIV-C2 were also
      obtained by the same way. All the mutants and chimeric F proteins were co
      expressed with their homologous or heterologous HN proteins in eukaryocytes. The
      fusion functions were assayed with Giemsa staining and reporter gene method for
      qualitative and quantitative analyses, respectively. The cell surface expression
      of F proteins was assayed with fluorescence-activated cell sorter (FACS) for
      quantitative analysis. RESULTS: All the mutants of F proteins had the same
      functions as their relevant wild types. Chimeric F proteins NDV-C1 and hPIV-C1
      had 76.34 and 65.82% of fusion activities, and NDV-C2 and hPIV-C2 had 96.25 and
      93.78% of fusion activities, respectively, as compared with their relevant wild
      types. The analysis of FACS indicated that all the mutants and chimeric F
      proteins had almost the same expression efficiencies as their relevant wild
      types. CONCLUSIONS: The segments of NDV F-1 and hPIV F-1 were important for their
      specific membrane fusion, but NDV F-2 and hPIV F-2 were not.

PMID- 17191012
TI  - Phylogenetic analysis of echovirus 11 in the 3' end of the VP1.
AB  - OBJECTIVE: Echovirus 11 is one of the most frequently isolated enterovirus
      serotypes, causing a wide range of clinical diseases. We studied the genetic
      diversity in the 3' end of the VP1 gene of strains from different geographical
      origin in the world. METHODS: The sequences in the 3' end of the VP1 of 11
      Tunisian isolates were determined and aligned with the published sequences to
      establish a phylogenetic profile. RESULTS: The grouping of the sequences was
      similar to what was previously reported by analyzing the whole VP1 gene with 4
      genogroups, designated A-D, and 5 lineages in genogroup D. All Tunisian strains
      belonged to genogroup D, together with other sequences mainly from the USA and
      Europe. Contrary to the sequences from the USA isolated during the last 3
      decades, which mostly belonged to the D4 lineage, those from Tunisia belonged to
      different lineages within genogroup D according to their isolation date: isolates
      from the early 1990s belonged to D3, those of the mid 1990s to D4 and the most
      recent ones to D5. CONCLUSION: Our findings further widen the interest of partial
      sequencing in the VP1 to study the molecular epidemiology of echovirus 11 and
      indicate that the genetic evolution of circulating strains may differ from one
      country to another according to the region's epidemiological specificities.

PMID- 17191014
TI  - Compositional bias and size of genomes of human DNA viruses.
AB  - Genomes of 144 human DNA viruses were analyzed in the aspect of their
      compositional asymmetry. DNA viruses were divided into two groups according to
      their genome sizes. The analysis revealed that the level of guanine and cytosine
      (GC content) in the coding sequences of small genome DNA viruses was
      significantly lower than that of large genome DNA viruses. Because small genome
      viruses replicate their genomes using cellular enzymes, while large genome
      viruses use their own enzymes for genome replication, the two groups of viruses
      may be under different mutational bias and/or selection pressure. In these
      viruses, GC content at the third codon position correlated with GC content at the
      first and second codon position. However, the relationship in small genome DNA
      viruses was weaker than that in large genome DNA viruses, suggesting that their
      genome composition may be more strongly influenced by codon usage preference or
      restriction on amino acid composition.

PMID- 17191015
TI  - Seroprevalence of hepatitis B and C viruses in patients with chronic kidney
      disease in the predialysis stage at a university hospital in Turkey.
AB  - BACKGROUND: Hepatitis B (HBV) and C (HCV) viruses are the most common viruses
      that cause viral infections among the hemodialysis patients. OBJECTIVES: To
      assess the prevalence of HBV and HCV in predialytic chronic kidney disease (CKD)
      patients. DESIGN: A cross-sectional study. SUBJECTS: 171 consecutive predialytic
      CKD patients. MEASUREMENTS: Third-generation micro-ELISA assay was used for
      hepatitis B surface antigen (HBsAg), antibody to hepatitis B core (anti-HBc) and
      surface antibody (anti-HBs), secretory form of hepatitis B envelop antigen
      (HBeAg), antibody to secretory form of hepatitis B envelop antigen (anti-HBe),
      and ELISA for antibody to hepatitis C virus (anti-HCV). RESULTS: The main causes
      of CKD were 29.8% diabetic nephropathy, 19.9% chronic glomerulonephritis, 16.3%
      hypertensive nephrosclerosis, 14.0% unknown, 5.3% amyloidosis, 4.7% autosomal
      dominant polycystic kidney disease, 4.1% chronic tubuluointerstitial nephritis,
      3.5% malignancies, 1.7% benign prostatic hypertrophy, 0.6% Alport syndrome. The
      seroprevalence of hepatitis was: HBsAg 10.5%, anti-HBc 36.8%, anti-HBs 28.7%,
      HBeAg 5.3%, anti-HBe 32.7%, anti-HCV 7% and HBsAg+anti-HCV 0.6%. CONCLUSIONS: The
      seroprevalence of HBsAg and anti-HCV among predialytic CKD patients was similar
      to our patients in hemodialysis program.

PMID- 17191016
TI  - Interferon therapy improves the irregular regeneration of hepatocytes in liver in
      patients with C-viral chronic hepatitis and liver cirrhosis.
AB  - We examined changes in the degree of irregular regeneration (IR) of hepatocytes
      and the F stage in patients with C-viral chronic hepatitis (CH) and liver
      cirrhosis (LC) who received interferon (IFN) therapy. The IFN-treated group
      consisted of 148 C-viral CH and LC patients; the IFN-untreated (UT) group
      consisted of 42 patients. The liver biopsy specimens were examined
      histologically, followed by a separate scoring of the degree of IR of hepatocytes
      which was classified into the following 5 grades and scored (IR score): score 0
      (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe). The annual rates of
      the IR score were -0.593 in sustained virologic responders, -0.188 in sustained
      biochemical responders, 0.071 in nonresponders and 0.121 in UT patients. The
      annual rates of the F stage were -0.218 in sustained virologic responders, -0.061
      in sustained biochemical responders, 0.123 in nonresponders and 0.157 in UT
      patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence
      was significantly higher in groups of IFN-treated patients without improvement of
      IR scores than in groups with improvement of IR scores. Multivariate analyses
      revealed that a lack of improvement in the IR score was a cardinal risk factor
      for the development of HCC in C-viral CH and LC patients. Our data suggest that
      IFN therapy leads to an improvement in the degree of IR of hepatocytes and
      thereby influences the development of HCC in patients with CH and LC.

PMID- 17191017
TI  - Heterogeneity of hepatitis B virus genotype D in Japan.
AB  - OBJECTIVE: Hepatitis B virus (HBV) genotypes B and C are predominant in Japan.
      Previously, we reported that approximately 9% of HBV carriers in the Ehime area
      of western Japan were infected with genotype D (HBV/D) and their sequences
      closely related. Recently, serum samples from 3 patients with chronic HBV/D
      infections living in Tokyo and the surrounding area became available for testing.
      The purpose of this study was to determine whether the HBV/D isolates from these
      different areas of Japan are closely related. METHODS: Of the 3 Tokyo area
      patients infected with HBV/D, 2 had chronic hepatitis, and 1 had hemophilia with
      a history of frequent coagulation factor injections. The complete HBV/D genome
      sequences of each were determined, and compared with those of subjects from the
      Ehime area. RESULTS: All 3 HBV/D sequences had a genomic length of 3,182 bases,
      and the hepatitis B surface antigen subtype was ayw3. Phylogenetic analysis
      revealed that the 1 of the HBV/D isolates was closely related to the isolates
      from Ehime Prefecture, while 1 was similar and 1 was clearly distinct.
      CONCLUSION: Our results indicate that HBV/D infections in Japan are
      heterogeneous.

PMID- 17191019
TI  - Inhibitory effect of quercetin on tryptase and MCP-1 chemokine release, and
      histidine decarboxylase mRNA transcription by human mast cell-1 cell line.
AB  - Mast cells are important in reactions of allergic disease and are also involved
      in a variety of neuroinflammatory diseases. Mast cells can be immunologically
      activated by IgE through their Fc receptors, as well as by neuropeptides and
      cytokines to secrete mediators. Here we used a human mast cell-1 (HMC-1) cell
      line cultured and treated with a physiological activator, anti-IgE, and a
      nonphysiological activator, calcium ionophore A23187, for tryptase and MCP-1
      generation and transcription of histidine decarboxylase. We used quercetin, a
      potent antioxidant, cytoprotective and anti-inflammatory compound capable of
      inhibiting histamine and some cytokines released from several cell types, as an
      inhibitor of immunological and nonimmunological stimulus for mast cells. In this
      study quercetin inhibits, in a dose-response manner, tryptase and MCP-1.
      Moreover, using RT-PCR quercetin inhibited the transcription of histidine
      decarboxylase, the rate-limiting enzyme responsible for the generation of
      histamine from histidine, and MCP-1. Our data suggest that quercetin is an
      important and good candidate for reducing the release of pro-inflammatory mast
      cell mediators activated by physiological and nonphysiological stimulators.

PMID- 17191018
TI  - The synergistic interaction of interferon types I and II leads to marked
      reduction in severe acute respiratory syndrome-associated coronavirus replication
      and increase in the expression of mRNAs for interferon-induced proteins.
AB  - Interferon (IFN)-alpha, -beta and -gamma have been shown to be only marginally
      effective against severe acute respiratory syndrome coronavirus (SARS-CoV)
      replication in Vero cell lines. We investigated the combination of type I IFNs
      (IFN-alpha or -beta) and IFN-gamma for antiviral activity and found that such
      combinations synergistically inhibited SARS-CoV replication in Vero cells, using
      yield reduction assay and the isobologram and combination index methods of Chou
      and Talalay for evaluation. The highly synergistic anti-SARS-CoV action of type I
      IFNs and IFN-gamma parallels the marked increase in 2'-5'-oligoadenylate
      synthetase and p56 mRNAs following exposure in Vero cells to either IFN-alpha or 
      beta and IFN-gamma compared with the transcriptional levels obtained after
      stimulation with either IFN alone. These results demonstrate that SARS-CoV,
      although only moderately sensitive to the antiviral action of the individual
      types of IFN, is highly sensitive to a combination of type I and II IFNs, which
      suggests that such combinations may have potential in the treatment of SARS-CoV
      infections.

PMID- 17191020
TI  - Association between plasma angiopoietin-like protein 3 and arterial wall
      thickness in healthy subjects.
AB  - BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is a liver-derived plasma
      protein that modulates plasma triglyceride clearance, angiogenesis and
      atherosclerosis in experimental models. So far, no study has examined its role in
      atherosclerosis in human subjects. We evaluated the possible association between
      plasma ANGPTL3 level and carotid artery intima-media thickness (CA-IMT) and
      femoral artery intima-media thickness (FA-IMT) in healthy human subjects.
      METHODS: The subjects were 381 healthy volunteers. Plasma ANGPTL3 was determined
      by a specific ELISA. CA-IMT and FA-IMT were measured by high-resolution B-mode
      ultrasonography. RESULTS: The plasma ANGPTL3 level was 764 +/- 291 ng/ml (mean +/
      SD). CA-IMT showed a significant positive correlation with plasma ANGPTL3 and
      other classical risk factors such as age, blood pressure, and plasma glucose and
      lipid levels. The positive association between ANGPTL3 and CA-IMT remained
      significant after adjustment for age, sex, smoking, body mass index, systolic
      blood pressure, plasma glucose, insulin resistance index, triglyceride, and high
      density and low-density lipoprotein cholesterol levels. ANGPTL3 also showed a
      positive association with FA-IMT independent of these factors. CONCLUSIONS: These
      results demonstrate for the first time that ANGPTL3 is closely associated with
      arterial wall thickness in human subjects.

PMID- 17191022
TI  - Impaired release of bioactive parathyroid hormone-related peptide in patients
      with pulmonary hypertension and endothelial dysfunction.
AB  - BACKGROUND: Parathyroid hormone-related protein (PTHrP) is an endothelial-derived
      vasoactive peptide. This study investigated whether bioactive PTHrP is locally
      released in a pressure-dependent way. METHODS: A PTHrP antibody directed against
      the midregional part of PTHrP was used to analyze PTHrP in plasma samples. The
      biological activity of this PTHrP-like peptide was investigated in vitro. Plasma
      values were determined in samples from the left pulmonary artery and the arteria
      femoralis, taken under basal conditions and after the application of oxygen or
      iloprost to lower the pulmonary pressure. Twenty young patients (mean age 6.5
      years), who were catheterized for an analysis of the reactivity of the pulmonary
      bed, were investigated. Endothelial function was investigated by acetylcholine
      responsiveness. RESULTS: The antibody recognized a 30-kDa protein with in vitro
      PTHrP-like activity. In 11 patients (responders) with intact endothelial
      function, the PTHrP values determined in the left pulmonary artery were higher
      than those in the arteria femoralis. The local increase in the PTHrP
      concentration was reduced when either oxygen or iloprost lowered the pressure.
      Nine patients with endothelial dysfunction did not show any concentration
      gradients at any time (nonresponders). CONCLUSIONS: The local concentration of
      bioactive PTHrP is increased in patients with pulmonary hypertension and normal
      endothelial function.

PMID- 17191021
TI  - Resveratrol, a polyphenolic phytostilbene, inhibits endothelial monocyte
      chemotactic protein-1 synthesis and secretion.
AB  - BACKGROUND/AIMS: Resveratrol is a naturally occurring polyphenol phytoestrogen
      and one of several constituents of red wine thought to be cardioprotective. We
      investigated the effect of resveratrol on the expression of the atherogenic
      chemokine, monocyte chemotactic protein-1 (MCP-1). METHODS: Human umbilical vein
      endothelial cells were stimulated with interleukin-1beta (IL-1beta) in the
      absence or presence of resveratrol. MCP-1 levels were determined by ELISA and MCP
      1 mRNA was measured. RESULTS: Resveratrol (1-100 microM) dose-dependently
      inhibited IL-1beta-stimulated MCP-1 secretion, with approximately 45% inhibition
      at 50 microM resveratrol. This was a Gi-protein- and NO-dependent effect.
      Resveratrol also significantly inhibited MCP-1 gene expression in a Gi-protein
      dependent but NO-independent manner. While resveratrol had no effect on MCP-1
      mRNA degradation, it inhibited MCP-1 promoter activity and reduced nuclear factor
      kappaB and activator protein-1 binding activity induced by IL-1beta. Moreover,
      while hemoxygenase-1 (HO-1) expression was induced by resveratrol in human
      umbilical vein endothelial cells, neither treatment with the HO-1 inhibitor tin
      protoporphyrin IX nor siRNA-directed knockdown of HO-1 had any effect on the
      inhibition of MCP-1 mRNA or protein secretion by resveratrol. CONCLUSION: These
      data demonstrate an inhibitory effect of resveratrol on MCP-1 synthesis and
      secretion, mediated via distinct signaling pathways. The inhibition of MCP-1 may
      represent a novel cardioprotective mechanism of resveratrol.

PMID- 17191023
TI  - High-fat- and lipid-induced insulin resistance in rats: the comparison of glucose
      metabolism, plasma resistin and adiponectin levels.
AB  - AIMS: In animal models, both an acute elevation in plasma free fatty acid (FFA)
      via intravenous infusion of a lipid emulsion and a chronic elevation in plasma
      FFA via high-fat feeding have been shown to induce skeletal muscle and liver
      insulin resistance. However, there have been very few studies comparing the
      effects of high-fat- and lipid-induced insulin resistance on glucose metabolism
      and adipocytokines. METHODS: In the current study, we used lipid infusion and a
      high-fat feed in combination with the hyperinsulinemic-euglycemic clamp technique
      to assess the impact of acute and chronically elevated FFA levels on overall
      glucose metabolism and insulin action; two adipocytokines, resistin and
      adiponectin, were used. RESULTS: At baseline, plasma FFA levels were
      significantly increased in the high-fat diet (HF) group compared to the control
      group (p < 0.05). During clamp steady-state, the FFA levels were reduced by
      approximately 25% in the control and approximately 48% in the HF groups. In
      contrast, there was a significant increase in the plasma FFA level in the lipid
      infused group (from 0.82 +/- 0.03 to 2.87 +/- 0.18 mmol/l). The glucose infusion
      rates (GIRs) in the HF and lipid groups were obviously lower than in the control
      group (p < 0.01). Moreover, GIR was lower in the lipid group compared with the HF
      group (p < 0.05). The rate of glucose disappearance (G(Rd)) was significantly
      lower in the lipid group compared with the control group. Hepatic glucose
      production in the control group was suppressed by approximately 15% compared with
      the HF and lipid groups where it was suppressed by only approximately 72 and
      approximately 91%, respectively. The resistin level of muscle tissues in the
      lipid group was significantly higher compared with the control and HF groups
      (both p < 0.05). After the insulin clamp, the circulating adiponectin level was
      significantly decreased in the lipid group compared with the control and HF
      groups (p < 0.05). CONCLUSIONS: Lipid infusion, which was more effective than a
      high-fat diet, can induce peripheral and hepatic insulin resistance in rats.
      Insulin-induced resistance might be associated with elevated resistin and
      decreased adiponectin.

PMID- 17191024
TI  - Distribution of anemia associated with micronutrient deficiencies other than iron
      in a probabilistic sample of Mexican children.
AB  - BACKGROUND: This investigation aims to explore the association among anemia and
      vitamins A, C, and folate deficiencies in a probabilistic sample of Mexican
      children. METHODS: Data on hemoglobin, serum vitamins A and C and folate
      concentrations and percent transferrin saturation (PTS) in children 0.5-11 years
      (n = 1,770) were extracted from the database of the probabilistic Mexican
      National Nutrition Survey 1999 (NNS-99). RESULTS: Overall, 16.6% of children were
      anemic. Iron deficiency children with or without anemia had more frequent low
      serum retinol (40.6 vs. 16% and 27.7 vs. 11.9%, p < 0.05, respectively) and lower
      hemoglobin folate (11.5 vs. 22%, p < 0.05) than their non-iron deficiency
      counterparts. Mean concentrations of serum iron (p < 0.01), folate (p < 0.001)
      and retinol (p < 0.0001), but not ascorbic acid (p < 0.6), were significantly
      lower in anemic than in nonanemic children. In a linear regression model, 15% of
      hemoglobin variation in children was explained by retinol, folate and PTS, but
      not vitamin C (p <0.0001). CONCLUSION: Anemia was mostly associated with iron
      deficiency and with a lesser proportion of folate and vitamin A deficiencies.
      Vitamin A deficiency might be overestimated since iron deficiency may lower serum
      retinol concentrations. Interventions aimed to reduce anemia in this population
      must consider interactions between those micronutrients in designing strategies.

PMID- 17191025
TI  - Dietary supplementation with chickpeas for at least 5 weeks results in small but
      significant reductions in serum total and low-density lipoprotein cholesterols in
      adult women and men.
AB  - AIM: To compare the effects of a chickpea-supplemented diet and those of a wheat
      supplemented diet on human serum lipids and lipoproteins. METHODS: Forty-seven
      free-living adults participated in a randomized crossover weight maintenance
      dietary intervention involving two dietary periods, chickpea-supplemented and
      wheat-supplemented diets, each of at least 5 weeks duration. RESULTS: The serum
      total cholesterol and low-density lipoprotein cholesterol levels were
      significantly lower (both p < 0.01) by 3.9 and 4.6%, respectively, after the
      chickpea-supplemented diet as compared with the wheat-supplemented diet. Protein
      (0.9% of energy, p = 0.01) and monounsaturated fat (3.3% of total fat, p < 0.001)
      intakes were slightly but significantly lower and the carbohydrate intake
      significantly higher (1.7% of energy, p < 0.001) on the chickpea-supplemented
      diet as compared with the wheat-supplemented diet. Multivariate analyses
      suggested that the differences in serum lipids were mainly due to small
      differences in polyunsaturated fatty acid and dietary fibre contents between the
      two intervention diets. CONCLUSIONS: Inclusion of chickpeas in an intervention
      diet results in lower serum total and low-density lipoprotein cholesterol levels
      as compared with a wheat-supplemented diet.

PMID- 17191026
TI  - Lupin (Lupinus albus) protein isolate (L-ISO) has adequate nutritional value and
      reduces large intestinal weight in rats after restricted and ad libitum feeding.
AB  - BACKGROUND: A protein isolate from white lupin (Lupinus albus; L-ISO) has
      potential as a novel human food ingredient, but its nutritional effects are
      unknown. METHODS: We evaluated protein quality and effects on body composition in
      rats of isoenergic diets of L-ISO, lactalbumin, or casein with both restricted
      (10-day) and ad libitum (28-day)intake. The diets were equivalent in protein per
      se, but supplementation was used to balance essential amino acid levels. RESULTS:
      In both studies, the rats consumed similar amounts of each diet, and no effect of
      diet on the gain:feed ratio was observed--though gain:N ratio and net protein
      utilization were slightly lower for the L-ISO diet. Lower large intestinal
      weights after the L-ISO than after the lactalbumin diet were observed in both
      studies. The L-ISO diet resulted in lowered body fat percentage in the 10-day
      study but in an elevated level in the 28-day study. Liver composition (DNA, RNA,
      glycogen, and fat) and plasma levels of some amino acids (His, Thr, Ala, Pro,
      Tyr, Val and Met) were affected by diet, but no effects on plasma lipid, glucose,
      or uric acid were observed. CONCLUSION: The L-ISO diet did not affect feed intake
      and has adequate nutritional quality in rats whilst modifying large intestinal
      weight in a potentially beneficial manner--suggesting potential for this protein
      in human nutrition.

PMID- 17191027
TI  - Use of botanicals in food supplements. Regulatory scope, scientific risk
      assessment and claim substantiation. 2005.
AB  - BACKGROUND/AIMS: In the European Union, an elaborate legal framework regulates
      botanical products both under food and medicinal law. The decision as to which
      legal framework applies to an individual product may differ between the Member
      States. In the case of botanical food supplements, all food law provisions apply
      to their manufacturing, composition and marketing, including the new claims
      legislation. METHODS: Elements from EU and national law, scientific and other
      publications are brought together to investigate how to clarify the
      differentiation between the use of botanicals for medicinal and health-promoting
      purposes on a scientific basis. RESULTS: Guidance on the safety assessment and
      quality evaluation of botanicals is proposed in light of the different approaches
      described in the scientific literature with particular attention to the concept
      of long-term use as an integral part of safety evaluation. Guidance on claims
      substantiation is also included, taking into consideration the proposed
      legislation, the concept of long-term experience and grading of evidence.
      CONCLUSIONS: A model for safety and efficacy assessment of botanical food
      supplements in the EU is proposed, and should be taken into consideration in the
      development of legislation and scientific research on botanicals.

PMID- 17191028
TI  - Anthropometric determinants of a clustering of lipid-related metabolic risk
      factors in overweight and non-overweight adolescents--influence of
      cardiorespiratory fitness. The Avena study.
AB  - BACKGROUND/AIMS: To explore in adolescents the associations between simple
      anthropometric variables with a continuously distributed summary score for lipid
      related metabolic risk in both overweight and non-overweight adolescents, and to
      test whether these associations are modified by the level of cardiorespiratory
      fitness. METHODS: Cardiorespiratory fitness, BMI, skinfold thicknesses, body
      circumferences, and a continuously distributed clustering of lipid- related
      metabolic risk (calculated from LDL and HDL cholesterol, triglycerides, and
      glucose) were measured in 524 adolescents (265 males, 259 females, 15.3 +/- 1.4
      years) from the cross-sectional multicentric AVENA study. Participants were
      classified as overweight (including obesity) or non-overweight. RESULTS: Most
      anthropometric parameters were univariately related to the continuous lipid
      related metabolic risk. However, after multicollinear analysis and generalized
      linear modelling, suprailiac skinfold thickness in males (p < 0.001, explained
      variance 12.2%) and waist-to-height ratio in females (p < 0.001, explained
      variance 10.0%) were the best determinants of the continuous metabolic risk
      score, after adjustment for age, sexual maturation, and economic status. These
      associations were slightly weakened in overweight males (p = 0.034) and females
      (p = 0.087), and did not interact with cardiorespiratory fitness. CONCLUSION: Our
      data emphasize the usefulness of suprailiac skinfold thickness in males and waist
      to-height ratio in females as simple anthropometric measurements associated to an
      overall lipid-related metabolic risk, mainly in non-overweight adolescents and
      regardless their cardiorespiratory status.

PMID- 17191029
TI  - Health-related quality of life in patients with pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is an aggressive cancer with low survival time,
      with health-related quality of life (HRQoL) being of major importance. The aim of
      our study was to assess both generic and disease-specific HRQoL in patients with
      pancreatic cancer. METHODS: Patients with pancreatic cancer were consecutively
      included at admission to hospital. HRQoL was determined with the disease-specific
      European Organization for Research and Treatment of Cancer (EORTC) and generic
      EuroQoL (EQ-5D) health status instruments. Scores of patients were compared to
      those of norm populations. The association of symptoms with overall HRQoL was
      analysed using linear regression. RESULTS: A total of 45 patients with pancreatic
      cancer were included. The mean age was 64 years, 53% were females. Of all
      patients, 44% had metastases at the time of admission. HRQoL was significantly
      impaired for most EORTC and EQ-5D scales in comparison to norm populations.
      Symptoms of fatigue (-0.34 regression coefficient; 95% CI -0.63, -0.11) and pain
      (-0.21; 95% CI -0.39, -0.02) were significantly associated with impaired overall
      HRQoL. CONCLUSIONS: HRQoL was severely impaired in patients with pancreatic
      cancer. Symptom control and palliative care appear to be of particular
      importance.

PMID- 17191030
TI  - Molecular pathogenesis of Kallmann's syndrome.
AB  - Hypogonadotrophic hypogonadism (HH) is characterized by delayed or absent
      pubertal development secondary to gonadotrophin deficiency. HH can result from
      mutations of the gonadotrophin-releasing hormone receptor 1, the gonadotrophin
      beta-subunits, or various transcription factors involved in pituitary gland
      development. HH occurs in DAX1 mutations when associated with adrenal
      insufficiency (adrenal hypoplasia congenita), and is also linked with obesity in
      patients with mutations of leptin and its receptor, as well as mutations in
      prohormone convertase 1. Rarely, HH has resulted from kisspeptin receptor (GPR54)
      mutations, a gene implicated in the regulation of pubertal onset. When occurring
      with anosmia (a lack of sense of smell), HH is referred to as Kallmann's syndrome
      (KS). Two KS-related loci are currently known: KAL1, encoding anosmin-1,
      responsible for X-linked KS, and KAL2, encoding the fibroblast growth factor
      receptor 1 (FGFR1), mutated in autosomal dominant KS. Anosmin-1 is an
      extracellular glycoprotein with some unique structural characteristics; it
      interacts with both urokinase-type plasminogen activator and FGFR1. It has
      previously been shown that anosmin-1 enhances FGFR1 signalling in a heparan
      sulphate-dependent manner, and proposed that anosmin-1 fine-tunes FGFR1
      signalling during olfactory and GnRH neuronal development. Here, we review the
      known normosmic causes of HH, and discuss novel developmental and molecular
      mechanisms underlying KS; finally, we introduce three novel genes (NELF, PKR2,
      and CHD7) that may be associated with some phenotypic features of KS.

PMID- 17191031
TI  - Macrosomic newborns of diabetic mothers are associated with increased aortic
      intima-media thickness and lipid concentrations.
AB  - BACKGROUND/AIMS: Exposure to diabetes in utero has been established as a
      significant risk factor for some of components of metabolic syndrome. A few
      studies have examined relationship between the metabolic syndrome and
      echocardiographic left ventricular (LV) mass. We aimed to investigate
      relationship between abdominal aortic intima-media thickness (aIMT), LV mass and
      lipid profile in macrosomic newborns. METHODS: Abdominal aIMT was measured in 30
      macrosomic neonates of diabetic mothers (group A), 30 macrosomic neonates of
      healthy mothers (group B) and 30 healthy neonates (group C). Lipid profile and LV
      mass were determined. RESULT: Mean aIMT was significantly higher in groups A and
      B (0.489 +/- 0.015, 0.466 +/- 0.019 mm, respectively) than in controls (0.375 +/-
      0.024 mm). Weight-adjusted aIMT in group A was significantly higher than in
      groups B and C. Macrosomia was associated with increased lipid concentrations.
      Both LV mass indexed for BSA (body surface area) and birth weight measurements
      were significantly increased in group A compared with control. CONCLUSIONS:
      Macrosomic neonates of diabetic mothers have significant aIMT and LV mass indexed
      for BSA and birth weight with lipid alterations. It might play a role in the
      pathogenesis of atherosclerosis in adult life.

PMID- 17191032
TI  - Time course of hyperosmolar opening of the blood-brain and blood-CSF barriers in
      spontaneously hypertensive rats.
AB  - The time course of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB)
      responses to hyperosmolar mannitol infusion (HMI; 1.6 M) during chronic
      hypertension was investigated using (14)C-sucrose as a marker of barrier
      integrity. (14)C-sucrose entry into CSF of both spontaneously hypertensive rats
      (SHR) and normotensive Wistar Kyoto (WKY) rats 2 min after HMI increased
      approximately 7-fold compared to their respective control. The volume of
      distribution (V(d)) of (14)C-sucrose into brain cortex of SHR increased 13-fold 2
      min after HMI while that in WKY rats increased only 4-fold. After HMI V(d) of
      (14)C-sucrose into the cortex of WKY, and CSF of both SHR and WKY remained
      steadily greater than their corresponding control for up to 30 min (p < 0.01),
      whereas in the cortex of SHR the V(d) of (14)C-sucrose reached control values 20
      min after HMI (p > 0.05), indicating that after HMI the increase in paracellular
      diffusion of (14)C-sucrose into SHR cortex was not persistent, in contrast to WKY
      rats and CSF of both SHR and WKY rats. Electron microscopy of the brain cortex
      after HMI showed capillary endothelial cell shrinkage and perivascular swellings
      in the brain cortex, and in the choroid plexus opening of tight junctions were
      observed. Our results indicate disruption of both the BBB and the BCSFB after HMI
      in both SHR and WKY rats. The disruption remained persistent up to 25 min after
      HMI at the BBB of WKY rats and BCSFB in both animal groups, while in SHR the
      protective function of the BBB returned to control values 20 min after HMI.

PMID- 17191033
TI  - Does renal function influence plasma levels of advanced glycation and oxidation
      protein products in patients with chronic rheumatic diseases complicated by
      secondary amyloidosis?
AB  - BACKGROUND: The aim of the study was to assess the contribution of carbonyl and
      oxidative stresses to the development of amyloidosis in patients suffering from
      chronic rheumatic diseases, and the potential influence of renal function to
      their concentrations was considered. METHODS: We investigated 17 patients with
      chronic rheumatological diseases and histologically proven diagnosis of AA
      amyloidosis (group AA-RA), 26 patients suffering from rheumatoid arthritis
      without any signs of AA amyloidosis (group nonAA-RA) and 20 healthy volunteers
      (Co). In all patients, advanced glycation end products (AGEs), advanced oxidation
      protein products (AOPP), pregnancy-associated plasma protein A (PAPP-A) and other
      selected proinflammatory markers were measured. RESULTS: An increase in serum
      levels of AOPP and AGEs was found in the AA-RA group in comparison with nonAA-RA
      patients and also with Co (p < 0.001 for all comparisons). AGEs positively
      correlated with serum creatinine (r = 0.67, p = 0.004) and negatively with
      glomerular filtration rate (r = -0.54, p = 0.027). We did not find a correlation
      between AOPP and any other assessed parameters including proteins and renal
      parameters. PAPP-A levels were not significantly increased in any group of
      patients (AA-RA, nonAA-RA) in comparison with Co. CONCLUSIONS: Increased plasma
      levels of AGEs and AOPP in the group of patients with AA-RA may have been partly
      explained by the diminished renal clearance. However, the increase in AOPP levels
      was higher than what is expected in this degree of renal failure (glomerular
      filtration rate in the AA-RA group corresponding to chronic kidney disease stage
      III).

PMID- 17191034
TI  - Effects of clozapine and sulpiride on morphine state-dependent memory in the step
      down passive avoidance test.
AB  - The effects of antipsychotic drugs sulpiride and clozapine on morphine state
      dependent memory of passive avoidance task were examined in mice. Post-training
      administration of morphine (5 mg/kg) led to state-dependent learning with
      impaired memory retrieval on the test day which was reversed by pre-test
      administration of the same dose of the opioid (5 mg/kg). In animals where memory
      was impaired by post-training morphine, the administration of either sulpiride or
      clozapine before pre-test morphine reduced the improvement of memory produced by
      the opioid. Co-administration of sulpiride with clozapine did not potentiate
      their antagonistic response. In conclusion, the inhibition of improvement of
      memory retrieval by morphine treatment on the test day by the two dopamine
      receptor antagonists seems to be induced through two different receptor
      mechanisms.

PMID- 17191035
TI  - A keratinocyte's course of life.
AB  - An adequate permeability barrier function of the mammalian epidermis is
      guaranteed by the characteristic architecture of the stratum corneum. This
      uppermost layer consists of a highly organized extracellular lipid compartment
      which is tightly joined to the corneocytes. The generation of the extracellular
      lipid compartment and the transformation of the keratinocytes into corneocytes
      are the main features of epidermal differentiation. However, equally important is
      the continuous renewal of the stratum corneum, which is insured by a careful
      balance between the replenishment of new keratinocytes from the proliferating
      basal layer, and the well-orchestrated loss of the most superficial cells after
      the so-called 'epidermal programmed cell death'. In this overview, the complete
      life of keratinocytes is described, from the proliferative organization to the
      process of desquamation.

PMID- 17191036
TI  - Assessment of topical corticosteroid activity using the vasoconstriction assay in
      healthy volunteers.
AB  - OBJECTIVE AND DESIGN: The aim of the study was to evaluate the vasoconstrictive
      activity of four new galenic preparations of hydrocortisone and to compare it
      with concentration-equivalent reference preparations. The study comprised two
      study phases: the pilot study phase and the main study phase. During open,
      nonrandomized pilot study, the optimal administration period was tested. The main
      study was performed in a randomized, double-blind intraindividual comparative
      design. SUBJECTS: Twenty male and female volunteers with healthy skin who
      responded to topically applied clobetasol-17-propionate before entering the trial
      participated in this study. TREATMENT: All subjects received the same treatments.
      The test preparations new galenic formulation (NGF) hydrocortisone 0.25% cream,
      NGF hydrocortisone acetate 0.25% cream, NGF hydrocortisone 0.5% cream, and NGF
      hydrocortisone 1.0% cream were compared with the respective reference
      preparations Soventol hydrocortisone (hydrocortisone acetate 0.25%), Hydroderm HC
      0.5% cream (hydrocortisone 0.5%), Hydrogalen cream (hydrocortisone 1.0%) and
      placebo (vehicle of test preparations). METHOD: The topical preparations were
      applied occlusively for 2 h (pilot study) or 24 h (main study) on outlined areas
      (5 x 5 cm with a distance of 3 cm) of both forearms (4 areas for each).
      Assessment of vasoconstriction was performed before treatment, and 0.5, 4, 6 and
      24 h after treatment (observation period) using a subjective rating scale (OLSEN
      vasoconstriction score) and measuring the colorimetric parameter a* (redness) by
      use of the Chroma-Meter (Minolta company, Ahrensburg, Germany). RESULTS: A
      significant vasoconstriction (positive blanching effect) was measured by use of
      chromametry for test preparations hydrocortisone 0.25% cream, hydrocortisone 0.5%
      cream, hydrocortisone 1.0% cream and for the reference preparation Hydrogalen
      cream compared to placebo 30 min after the end of treatment. In contrast, the
      reference preparations Soventol hydrocortisone and Hydroderm HC 0.5% did not
      differ significantly from placebo 30 min after treatment. No statistically
      significant effect of all formulations was observed 4-24 h after treatment in
      comparison with placebo. CONCLUSIONS: The vasoconstrictive efficacy of test
      preparations was mostly stronger than the concentration-equivalent reference
      preparations. This effect was achieved by use of new galenics of test
      preparations resulting in enhanced skin penetration and improved efficiency. No
      unwanted side effects were observed during the course of the study despite
      increased efficacy of the topically applied test preparations.

PMID- 17191037
TI  - Thoracoscopy: origins revisited.
AB  - The ways in which thoracoscopy has evolved wonderfully illustrate how a
      diagnostic and therapeutic technique can transcend a particular medical or
      surgical subspecialty. In this review, an in-depth history is provided to enable
      readers to better understand the nature of minimally invasive endoscopic pleural
      imaging techniques.

PMID- 17191038
TI  - SDRIFE - another acronym for a distinct cutaneous drug exanthema: do we really
      need it?

PMID- 17191039
TI  - Dermoscopy key points: recommendations from the international dermoscopy society.

PMID- 17191040
TI  - The price for treatment of chronic skin diseases: different approaches.

PMID- 17191041
TI  - Decreased serum tryptophan concentration predicts poor prognosis in malignant
      melanoma patients.
AB  - BACKGROUND: Indoleamine (2,3)-dioxygenase (IDO) catalyses the initial, rate
      limiting step in the degradation of the essential amino acid tryptophan. Via
      tryptophan deprivation, IDO activity suppresses T cell proliferation and
      differentiation and is thought to be a fundamental immune escape mechanism for
      tumor cells. OBJECTIVE AND METHODS: To investigate the potential role of
      tryptophan degradation as a prognostic marker, serum tryptophan and kynurenine
      concentrations and the kynurenine-to-tryptophan ratio (kyn/trp) in 87 patients
      with malignant melanoma were compared to the course of the disease and to
      concentrations of the immune activation marker neopterin. RESULTS: Compared to 49
      healthy volunteers, the melanoma patients presented with lower tryptophan levels
      due to accelerated degradation. This was especially true for the subgroups of
      patients with distant metastases (p = 0.01), though not in patients with lymph
      node metastases or in patients who had not yet progressed. There existed a
      positive correlation between kyn/trp and neopterin concentrations (r(s) = 0.587,
      p <0.001). In patients who died due to dissemination of the tumor, median
      tryptophan concentrations were significantly decreased (p = 0.006) and kyn/trp (p
      = 0.03) and neopterin concentrations (p = 0.002) were higher compared to
      survivors. In addition, lower tryptophan concentrations as well as higher kyn/trp
      and neopterin concentrations predicted a shorter survival. CONCLUSION: Decreased
      serum tryptophan concentrations and elevated serum neopterin levels can be used
      as predictive markers for the future course in melanoma patients. Moreover, our
      data support previous speculations that a higher degree of IDO expression could
      play a crucial role for tumor progression.

PMID- 17191042
TI  - C-kit Asp-816-Val mutation analysis in patients with mastocytosis.
AB  - BACKGROUND: Mastocytosis is a heterogeneous group of disorders characterized by
      abnormal accumulation of mast cells. OBJECTIVE: Skin biopsies from 24 patients
      (23 with proven mastocytosis) were screened for the presence of the c-kit Asp-816
      Val mutation. METHODS: In frozen biopsies, RNA was isolated, cDNA synthesis and
      PCR, the expected PCR product of 346 bp was obtained from 23 patients. RESULTS:
      In patients with urticaria pigmentosa, the mutation was detected in 38% of the
      adults and 25% of the children. With regard to the clinical presentation of the
      disease, no difference was found between adult patients with and without the
      mutation, as detected with our assay. One out of the 2 children with the mutation
      had an atypical presentation of the disease. CONCLUSION: the mutation could not
      be detected in all the patients, probably due to lack of sensitivity of the
      methods.

PMID- 17191043
TI  - Videocapillaroscopy in the differential diagnosis between psoriasis and
      seborrheic dermatitis of the scalp.
AB  - BACKGROUND: Videocapillaroscopy (VCP) can be used to explore microcirculatory
      modifications in skin diseases. Psoriasis shows specific capillary alterations
      reflecting typical histopathological changes. OBJECTIVE: To compare capillary
      morphology, distribution and density in psoriasis and seborrheic dermatitis of
      the scalp for differential diagnosis. METHODS: VCP was performed on histology
      confirmed scalp lesions of 30 patients with chronic plaque psoriasis, 30 age- and
      sex-matched patients with seborrheic dermatitis and 30 healthy subjects. The
      morphology, mean density per mm(2) and mean diameter of capillary loops was
      measured. RESULTS: Scalp psoriasis exhibited homogeneously tortuous and dilated
      capillaries (bushy pattern), with a 73 +/- 17 mum (mean +/- standard deviation)
      diameter of capillary bushes. In contrast, scalp seborrheic dermatitis presented
      a multiform pattern, with mildly tortuous capillary loops and isolated dilated
      capillaries, but a substantial preservation of local microangioarchitecture. Mean
      diameter of capillary bush was significantly lower (27 +/- 4 microm; p < 0.001)
      and similar to that of the scalp of healthy subjects (21 +/- 5 microm). Capillary
      loop density was similar in patients with psoriasis (23 +/- 5/mm(2)) seborrheic
      dermatitis (24 +/- 2/mm(2)) and healthy scalp skin (24 +/- 3/mm(2)). CONCLUSION:
      VCP could be a useful noninvasive approach for differentiating between psoriasis
      and seborrheic dermatitis, especially when the scalp is the only affected site.

PMID- 17191044
TI  - Multiple large solar lentigos on the upper back as clinical markers of past
      severe sunburn: a case-control study.
AB  - BACKGROUND: Multiple solar lentigos commonly seen on the upper back and shoulders
      of adults are classically considered as a sign of photodamage, although
      epidemiological studies are scarce. AIM: To assess whether these lesions are
      clinical markers of past severe sunburn. METHODS: A case-control study in two
      outpatient dermatology clinics in French university hospitals. Past episodes of
      moderate and severe sunburn were compared between 145 adult patients with
      multiple solar lentigos on the upper back and 145 matched controls. RESULTS: In
      multivariate analysis adjusted for potential confounders, recalled episodes of
      sunburn during childhood, adolescence and adulthood were independently associated
      with the presence of multiple solar lentigos (adjusted odds ratios, 95%
      confidence intervals: 2.3 (1.1-5.2) and 28.1 (10.4-75.6) for moderate and severe
      sunburn, respectively). CONCLUSION: Multiple solar lentigos on the upper back and
      shoulders of adults are potential clinical markers of past severe sunburn which
      may thus be used to identify a population at higher risk of developing cutaneous
      malignant melanoma.

PMID- 17191045
TI  - Pregnancy and pregnancy outcome among women with inflammatory skin diseases.
AB  - BACKGROUND/AIMS: The effect of inflammatory skin diseases on pregnancy has been
      incompletely characterized. We sought to estimate the incidence of pregnancy and
      pregnancy outcomes among women with inflammatory skin diseases. METHODS: Cohort
      study of women with atopic dermatitis (AD), psoriasis, other inflammatory skin
      diseases, and comparison group, followed for pregnancies and pregnancy outcomes.
      RESULTS: There were 3,131 pregnancies among 64,773 woman-years (4.8/100) in women
      with skin diseases, and 2,592 pregnancies among 59,826 woman-years (4.3/100) in
      the comparison group. The age-standardized incidence of pregnancy was similar to
      the comparison group [rate ratio (RR) = 1.2, 95% confidence interval (CI) 1.0-1.4
      for AD, RR = 1.1, 95% CI 1.0-1.2 for psoriasis, and RR = 1.1, 95% CI 1.0-1.1 for
      other]. Spontaneous abortion was also similar to the comparison group (RR = 1.2
      for AD, 95% CI 1.0-1.4, RR = 1.1, 95% CI 1.0-1.2 for psoriasis, and RR = 1.1, 95%
      CI 1.0-1.1 for other). CONCLUSIONS: Our results suggest little effect of skin
      disease on incidence or outcome of pregnancy.

PMID- 17191046
TI  - SACRAL syndrome: spinal dysraphism, anogenital, cutaneous, renal and urologic
      anomalies, associated with an angioma of lumbosacral localization.
AB  - BACKGROUND: Publications concerning perineal infantile hemangiomas are scarce,
      and comprise no large series. OBJECTIVE: Studying clinical features of
      hemangiomas of the perineal area, complications and associated malformations.
      METHODS: Retrospective analysis of all hemangiomas localized in the perineal
      area, encountered at the Children's Hospital in Bordeaux from 1994. RESULTS: Of
      49 perineal hemangiomas (34 girls, 15 boys), 5 patients had accompanying
      malformation, mainly lipomyelomeningocele with tethered cord. The superficial
      hemangiomas were more represented in males and presented sooner than the nodular
      counterpart. The average rate of ulceration was 73%, ulcerations developed
      earlier in the superficial forms than their nodular counterparts (2 vs. 4
      months). CONCLUSION: Superficial perineal hemangiomas are more often complicated
      by ulceration, and are associated with developmental anomalies. As a counterpart
      for the PHACE syndrome in facial hemangioma, we propose the acronym SACRAL for
      perineal hemangiomas: Spinal dysraphism, Anogenital anomalies, Cutaneous
      anomalies, Renal and urologic anomalies, associated with Angioma of Lumbosacral
      localization.

PMID- 17191047
TI  - ECCA grading scale: an original validated acne scar grading scale for clinical
      practice in dermatology.
AB  - INTRODUCTION: The ECCA grading scale (echelle d'evaluation clinique des
      cicatrices d'acne) is a tool designed to help dermatologists to assess the
      severity of acne scars and to standardize the discussions about the treatments of
      scars. METHODS: We developed an acne scar clinical grading scale called ECCA,
      which consists of 6 items designed to assess easily and quickly the severity of
      acne scars by a global score. The interobserver reliability of the ECCA grading
      was statistically validated. RESULTS: The statistical analysis showed the
      interinvestigator reliability of the ECCA grading scale among 7 dermatologists
      who used it on the same group of 10 acne patients. CONCLUSION: ECCA is a new tool
      which will now be available for dermatologists to use in their everyday practice
      and for clinical trials evaluating the efficacy of treatments on acne scars.

PMID- 17191048
TI  - Recurrent erysipelas: 47 cases.
AB  - BACKGROUND: Recurrence is a common complication of erysipelas (cellulitis).
      OBJECTIVES: Todescribe the characteristics of patients with recurrent erysipelas
      and thereby, identify potential risk factors and evaluate prophylaxis efficacy.
      METHODS: Data were retrospectively recorded from the files of 47 patients
      admitted to hospital between 1995 and 2003 for erysipelas recurrence. Studied
      variables included: general condition, regional and local factors, e.g. broken
      cutaneous barrier. Patient characteristics were used to construct tree-based
      models according to the classification and regression tree methodology. RESULTS:
      Our patients suffered a mean of 4.1 recurrences. Cutaneous barrier disruption was
      observed in 81%, mainly intertrigo (60%). Antibiotic prophylaxis was taken by 68%
      of the patients for 30.6 months. After 1 and 2 years, 84 and 72% of the patients,
      respectively, were recurrence-free. CONCLUSION: Our results showed that
      erysipelas recurrence has the same risk factors as single episodes and underlines
      the potential benefit of oral or parenteral antibiotic prophylaxis to prevent
      recurrences.

PMID- 17191049
TI  - Scleromyxedema: successful treatment with thalidomide in two patients.
AB  - BACKGROUND: Scleromyxedema is an unusual skin disease characterized by mucinous
      infiltration of the skin. There is no satisfactory treatment for this disorder.
      CASE REPORT: We report 2 cases of scleromyxedema, both associated with an IgG
      lambda paraprotein. Treatment with thalidomide was started and great improvement
      of the lesion was noted as shown by a quality of life questionnaire similar to
      those used in rheumatoid arthritis. TNF-alpha value was elevated in both cases
      during this treatment. DISCUSSION: We hypothesize that the efficiency of
      thalidomide could be mediated by its costimulatory effect on T cytotoxic
      lymphocytes.

PMID- 17191050
TI  - The steroid-sparing effect of an emollient therapy in infants with atopic
      dermatitis: a randomized controlled study.
AB  - BACKGROUND: No study has clearly demonstrated the steroid-sparing effect of
      emollients in the treatment of atopic dermatitis (AD). AIM: Evaluating the effect
      of an emollient containing oat extracts on the amount of topical corticosteroids
      used in infants with moderate to severe AD. STUDY DESIGN: During 6 weeks, 173
      infants under 12 months old treated for inflammatory lesions by moderate- and/or
      high-potency topical corticosteroids randomly received the emollient or not
      (control group). METHODS: Evaluation of corticosteroid consumption by weighing
      the tubes, disease severity by the Scoring Atopic Dermatitis Index (SCORAD), and
      infants' and parents' quality of life by Infant's Dermatitis Quality of Life
      Index and Dermatitis Family Impact scores at D0, D21 and D42. RESULTS: Compared
      to the control group, the amount of moderate- and high-potency corticosteroids
      used in 6 weeks decreased by 7.5% (not significant) and 42% (p < 0.05),
      respectively, in the emollient group. The SCORAD index, and infants' and parents'
      quality of life significantly improved (p < 0.0001) in both groups. CONCLUSION:
      The emollient treatment significantly reduced the high-potency topical
      corticosteroid consumption in infants with AD.

PMID- 17191051
TI  - Effectiveness of inpatient treatment on quality of life and clinical disease
      severity in atopic dermatitis and psoriasis vulgaris - a prospective study.
AB  - BACKGROUND: Financial constraints challenge evidence of the effectiveness of
      dermatological inpatient management. OBJECTIVE: To evaluate the effectiveness of
      hospitalization in atopic dermatitis and psoriasis regarding initial and
      sustained benefits. METHODS: Prospective study on adults with psoriasis vulgaris
      (n = 22) and atopic dermatitis (n = 14). At admission, discharge, and 3 months
      after discharge, validated outcomes of objective and subjective disease severity
      were assessed by trained investigators. RESULTS: Hospitalization resulted in
      substantial benefit in quality of life and clinical disease severity. Looking at
      mean scores, the observed benefit appeared stable until 3-month follow-up. The
      analysis of individual patient data revealed significant changes in disease
      severity between discharge and 3-month follow-up with some patients relapsing,
      others further improving. Reasons for hospitalization and treatment performed
      were not related to sustained benefit. CONCLUSIONS: In psoriasis vulgaris and
      atopic dermatitis, hospitalization effectively improved quality of life and
      clinical disease severity. Further research should focus on prognostic factors
      for sustained improvement.

PMID- 17191052
TI  - Pyoderma vegetans associated with severe psoriatic arthritis: good response to
      etanercept.
AB  - Pyoderma vegetans (PV) is an inflammatory dermatosis, characterized clinically by
      large exudative vegetating plaques, and histopathologically by epidermal
      pseudoepitheliomatous hyperplasia and dense inflammatory infiltrates. Although PV
      is a very rare condition, it is a chronic disorder that may accompany any
      systemic process that compromises immunity. Treatment is very difficult, and
      correction of predisposing causes may be useful. We present a 49-year-old woman
      affected by severe psoriatic arthritis since she was 19, with giant verrucous
      plaques on her lower limbs that had worsened progressively during the last 15
      years. After ruling out other vegetating cutaneous disorders, PV was diagnosed in
      association with psoriasis. Despite numerous previous systemic and topical
      therapeutic attempts no response was observed. Etanercept was introduced, which
      resulted in a marked improvement within 3 weeks. Herein, we report a diagnostic
      and therapeutic challenge of the first case of PV associated with psoriasis that
      presented a good response to etanercept.

PMID- 17191053
TI  - Hemosiderotic dermatofibroma: report of one case.
AB  - Dermatofibroma (DF) is a common benign fibrohistiocytic lesion which presents
      with a wide variety of clinicopathological features. Generally, the clinical
      diagnosis is easy, but differentiating it from other cutaneous tumors could be
      difficult in atypical cases and rare variants. We may find at least four
      different histopathological variants of DF; more than one of which may be present
      in a single tumor. Hemosiderotic DF is a variant composed of numerous small
      vessels, extravasated erythrocytes, and intra- and extracellular hemosiderotic
      deposits. The differential diagnosis may comprise melanoma as well as other
      melanocytic and nonmelanocytic tumors. We report the case of a 38-year-old man
      who presented with a hemosiderotic DF on the abdomen.

PMID- 17191054
TI  - Anti-SSA/Ro antibody as a risk factor for fluorouracil-induced drug eruptions
      showing acral erythema and discoid-lupus-erythematosus-like lesions.
AB  - BACKGROUND: It is well known that fluorouracil (FU) agents frequently induce
      discoid-lupus-erythematosus (DLE)-like eruptions and acral erythema in Japan.
      However, the etiology of these drug eruptions caused by FU agents has not been
      clarified yet. OBJECTIVE: To determine if the existence of anti-SSA/Ro antibody
      may be a risk factor for FU-agent-induced DLE-like eruptions and acral erythema.
      PATIENTS AND METHODS: Six patients with FU-agent-induced drug eruptions showing
      DLE-like lesions and acral erythema were enrolled in this study. The titers of
      anti-SSA/Ro antibody in the sera and the histopathology of the skin lesions were
      examined. RESULTS: Biopsy specimens from DLE-like eruptions and all 5 examined
      acral erythema cases showed lichenoid change of the basal keratinocytes. Direct
      immunofluorescence studies revealed deposition of immunoglobulins along the
      basement membrane zone in the lesions of both DLE-like eruptions and acral
      erythema. Further, all 6 cases had high titers of serum anti-SSA/Ro antibody,
      which did not decline within 6 months after cessation of the causative drug.
      CONCLUSION: We propose that anti-SSA/Ro antibody may be a risk factor for FU
      agent-induced drug eruptions showing acral erythema and DLE-like eruptions.

PMID- 17191055
TI  - Recurrent flexural exanthema (SDRIFE or baboon syndrome) after administration of
      two different iodinated radio contrast media.
AB  - In 1984, the baboon syndrome was described as a particular form of systemic
      contact dermatitis that occurred after the administration of a contact allergen
      in individuals previously sensitized by topical exposure to the same allergen.
      Its clinical picture presents as an erythema of the buttocks and upper inner
      thighs resembling the red bottom of baboons. This specific reaction was
      originally observed with mercury, nickel and ampicillin. Since then over 100
      cases have been described, most of them without known prior sensitization to the
      causative agent. In 2004, our group proposed the acronym SDRIFE specifically for
      cases associated with systemic drugs; it stands for symmetrical drug-related
      intertriginous and flexural exanthema, as a distinct reaction pattern related to
      systemic drugs. Here we describe a case of SDRIFE after administration of the
      iodinated radio contrast medium (RCM) iomeprol (Iomeron), accidentally reproduced
      by the RCM iopromide (Ultravist). Positive delayed skin tests with both drugs
      were observed indicating that the pathomechanism of SDRIFE is likely a cell
      mediated type IV allergy. Oral potassium iodide and a skin-test-negative RCM were
      administered and both tolerated, indicating that the antigen is related to the
      molecules and not to iodine itself. Therefore, in our case skin tests had a good
      positive and negative predictive value.

PMID- 17191056
TI  - Cutaneous pseudolymphoma induced by Cimicifuga racemosa.
AB  - We report a 56-year-old female patient who presented with asymptomatic, localized
      erythematous plaques on arms and legs. Histologically, the diagnosis of
      pseudolymphoma (PL) was confirmed. Because of menopausal complaints, the patient
      had been taking Remifemin(R), a phytotherapeutical agent containing a
      standardized extract of black cohosh (Cimicifuga racemosa) rhizome for 1 year.
      Six months after initial administration of this herbal drug, first skin lesions
      appeared which continuously increased. Withdrawal of Remifemin resulted in
      regression and complete remission of the lesions within 12 weeks. To the best of
      our knowledge, this is the first report on cutaneous PL induced by a standardized
      extract of C. racemosa rhizoma. Thus, though claimed to be poor in adverse
      effects, the potency of phytotherapeutical agents to induce uncommon cutaneous
      eruptions needs to be taken into careful reconsideration since the course of
      cutaneous PL tends to be chronic and indolent if the causative agent is not
      discontinued.

PMID- 17191057
TI  - Photosensitive lichenoid eruption and inhaled tiotropium bromide.

PMID- 17191058
TI  - Long-term efficacy of occlusive therapy with topical pimecrolimus in severe
      dyshidrosiform hand and foot eczema.

PMID- 17191059
TI  - Topical use of minoxidil in children and systemic side effects.

PMID- 17191060
TI  - Evaluation of diametral tensile strength and Knoop microhardness of five
      nanofilled composites in dentin and enamel shades.
AB  - The purpose of this study was to evaluate and compare the mechanical behavior of
      five nanofilled composites with dentin and enamel shades trough diametral tensile
      strength and knoop microhardness. 4 Seasons (Ivoclar Vivadent), Esthet X improved
      (Dentsply), Filtek Supreme (3M), Grandio (Voco) and Palfique Estelite (Tokuyama
      Dental Corp.) were used in this research. Twenty samples (6 mm diameter and 3 mm
      thickness) of each material were used. Ten samples were submitted to knoop
      microhardness and the others to diametral tensile strength examinations. The
      results were submitted to ANOVA and Tukey statistical tests (a=0.05). There were
      significant differences between the tested groups (p<0.05). The diametral tensile
      strength ranged from 36.08 (4 Seansons dentin) to 49.24 (Grandio enamel). The
      knoop microhardness ranged from 54.45 (Esthet X improved enamel) to 123.90
      (Grandio dentin). A great variability in the mechanical behavior of the
      nanofilled composites was observed. However it was not recorded with dentin and
      enamel shades with the exception of Grandio.

PMID- 17191061
TI  - A scanning electron microscopic study of debris and smear layer remaining
      following use of AET instruments and K-flexofiles.
AB  - AIM: To compare in vitro the cleanliness of root canal walls following automated
      or manual instrumentation. METHODOLOGY: Thirty extracted human maxillary central
      incisors, maxillary and mandibular canines and premolars with single root canals
      were used in this study. The teeth were divided into two groups. In group 1 (20
      teeth) automated canal preparation was performed using Anatomic Endodontic
      Technology (AET). In group 2 (10 teeth) manual instrumentation was performed with
      K-Flexofiles. Irrigation was performed using alternately 3.00% NaOCl and 18%
      EDTA, followed by rinsing with saline. The roots were split longitudinally into
      halves and the canals examined using a scanning electron microscope. The presence
      of debris and smear layer was recorded at coronal, middle and apical thirds of
      root canals using a four-step scoring scale. Mean scores for debris and smear
      layer were calculated and statistically analysed for significance (P<0.05)
      between and within groups, using the Mann-Whitney-Wilcoxon and Friedman
      nonparametric tests. RESULTS: At coronal and middle thirds the root canals
      prepared with manual instrumentation had significantly less surface debris on the
      canal walls compared with canals prepared with AET (p<0.05). At apical third root
      canals prepared with manual instrumentation had significantly more debris
      compared with AET group. The amount of smear layer was greater in the apical than
      in the coronal and middle thirds of the root and significantly less amount was in
      the AET group (P<0.05). CONCLUSIONS: Complete cleanliness was not achieved by any
      of the techniques and instruments investigated. It may be inferred that the
      choice between AET and hand instrumentation should be based on factors other than
      the amount of root canal debridement, which does not vary high significantly
      according to the instruments used.

PMID- 17191062
TI  - Factors related to apical root resorption of maxillary incisors in orthodontic
      patients.
AB  - THE MAIN OBJECTIVE of the study was to determine the extent of external apical
      root resorption at the end of orthodontic treatment and to identify the possible
      pre-treatment and treatment factors that would allow to predict the possible
      incidence of root resorption before the start of treatment. PATIENTS AND METHODS:
      Panoramic radiographs of 75 patients that had been treated with full fixed
      appliances were used to assess apical root resorption in maxillary incisors. The
      degree of root resorption was measured in millimetres and the scale of Shape was
      used. RESULTS: The results showed that the resorption in the maxillary incisors
      is on the average 1.5 mm, the severe resorption was seen in 2.6% of patients. The
      worst resorption was seen in teeth with abnormal root shape. There were no
      differences in the severity of root resorption when comparing males and females
      as well as children and adults. Increased overjet, overbite and extraction
      therapy were not associated with greater root resorption. Duration of treatment
      and length of treatment time with rectangular wires were associated with greater
      root resorption. Patients wearing composite brackets with a metal slot had more
      resorption than patients wearing metal brackets. CONCLUSION: Pre-treatment risk
      indicator for root resorption was abnormal root shape. Risk indicators for root
      resorption that were related to treatment procedures included length of treatment
      time with rectangular wires, duration of treatment and treatment with composite
      brackets with a metal slot.

PMID- 17191063
TI  - Effect of the lower third molars on the lower dental arch crowding.
AB  - Increasing lower dental arch crowding with the age is a recognized clinical
      problem, and one that has become more apparent in recent years as more adults
      retain their teeth longer. One of the theories is that the erupting third molars
      push anterior teeth forward and cause their crowding. On the other hand, a number
      of studies found no correlation between lower third molars and lower incisor
      crowding. Because of all these contrasting findings this study was started to re
      evaluate correlation between third molars presence and lower dental arch
      crowding. The study group consisted of 91 subjects with an average age 21.01+/
      4.13 years. The individual, quantitative and cast-based analytical registration
      of crowding was based on the measurements of mesiodistal width of teeth and
      related to the length of the appropriate segment of the lower dental arch. No
      statistically significant third molar presence-specific differences were recorded
      in the lower dental arch crowding between the groups with erupted, unerupted and
      agenesis of third molars. Although differences between the groups were not
      statistically significant, some tendency for crowding in the anterior part of
      lower dental arch was more expressed in the groups with the presence (erupted
      0.57 mm and unerupted 0.74 mm) of third molars, than with agenesis (surplus space
      0.03 mm). Nevertheless, the present study do not provide enough evidence to
      incriminate third molars as being the only or even major etiologic factor in the
      late lower dental arch crowding.

PMID- 17191064
TI  - Changes in the periodontal condition after replacement of swaged crowns by metal.
AB  - Evidence based clinical studies have shown exact recommended design for
      artificial crown reconstruction with acceptable long-term results taking into an
      account the biological price. Previous histological and clinical studies proved
      that fixed prostheses might influence the periodontal condition of crowned teeth,
      if not all biological criteria have been considered. The aim of the present study
      was to assess the periodontal condition of the crowned teeth after stainless
      steel swaged crowns were replaced by cast metal ceramic crowns. Participants were
      selected at the Institute of Stomatology, Stradin's University. Selection
      criteria included need to replace existing swaged crowns by metal ceramic crowns
      for patients with absence of any systemic disease. Following symptoms of
      periodontal condition were examined - presence of inflammation (clinical signs,
      probing) and pocket depth. Assessments were carried out at four different points
      of time (first appointment after replacement existing swaged crowns by temporary
      crowns; two weeks after cementation of permanent metal ceramic restoration; after
      three month; after six month). Overall bleeding score "2" and "3" at the first
      measurement was observed in majority of study population. Bleeding scores between
      the 1st and the 4th measurement was significantly lower (p<0.01). The same trend
      was observed also in the reduction of pocket depth. Overall mean value of pocket
      depth gradually decreased from the 1st till the 4th measurement. Replacement of
      swaged crowns by metal ceramic improves gingival health and leads to better long
      term prognosis for restored teeth. It is recommended that swaged crowns be
      replaced with more biologically friendly crowns.

PMID- 17191065
TI  - Surgical lengthening of the clinical tooth crown.
AB  - To understand why the crown lengthening may be desirable, a review of periodontal
      anatomy is in order. The odontologists know, but often underestimate importance
      of periodontal tissues health to restoration of defected teeth or dental arches.
      In order to avoid pathological changes, to predict treatment results more
      precisely, it is necessary to keep gingival biological width unaltered during
      teeth restoration. If there are less than 2 mm from restoration's margin to
      marginal bone clinical crown lengthening possibility should be considered in
      dental treatment plan. The choice depends on relationship of crown-root-alveolar
      bone and esthetical expectations. In order to keep margins of restoration
      supragingivally the distance from marginal bone to margins of restoration should
      not be less than 3 mm. Ideally the margins of restoration should be
      supragingivally or in the same level as marginal gingiva. When the margins of
      restoration are prepared subgingivally, the distance from marginal gingiva to
      margins of restoration should not be more than 0.7 mm. To continue dental
      treatment in operated area is recommended not earlier than in 4 weeks, and making
      restorations in esthetical area--not earlier than in 6 weeks.

PMID- 17191067
TI  - Breeding and building molecules to spy on cells and tumors.

PMID- 17191066
TI  - The relationship between blood serum lipids and periodontal condition.
AB  - THE AIM OF THE STUDY: the study analyzed he relationship between blood serum
      lipids and periodontal condition, as well as the relationship between the left
      ventricular mass index and the condition of periodontium. The study included 261
      subjects--140 women and 121 men. Mean age of the subjects was 38 years. The
      condition of periodontal tissues during the study was evaluated with the help of
      the CPITN index (Community Periodontal Index of Treatment Needs). The study was
      performed at Kaunas University of Medicine (KMU) Clinic of Dental and Oral
      Diseases. Laboratory blood lipid studies were performed at the laboratory of the
      Hospital of Kaunas University of Medicine (HKUM). The studies included the
      determination of the total blood cholesterol level, triglyceride level, HDL
      cholesterol level, and LDL cholesterol level (mmol/l). Patients with hypertension
      (102 patients) underwent ultrasound examination of the heart at KMU Clinic of
      Cardiology. On the basis of the findings of the ultrasound study, left
      ventricular mass index (g/m(2)) was calculated. The findings of our study showed
      that there was no difference in the blood serum concentration of total
      cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol between people
      with healthy periodontium and those with gingivitis or periodontitis. Mean rank
      of the left ventricular mass index in subjects with healthy periodontium or
      gingivitis (CPITN codes 0, 1, 2) was 48.3, and in subjects with periodontitis
      (CPITN codes 3, 4) - 61.36 (p<0.05).

PMID- 17191068
TI  - Perspectives in medical education. 3. Reforming medical education to change
      healthcare practice in Japan.
AB  - The enviable health status of Japanese citizens is one of the reasons for
      obdurate opposition to reform of Japanese healthcare practice. Change is widely
      believed to be unnecessary for a system that is both successful and profitably
      exploited to universal benefit. However, societal trends are conspiring to make
      current healthcare practice patterns and expenditures unsustainable in the
      future. In particular, Japan has undergone an unprecedented demographic shift
      from a society of young (and healthy) workers to one of older retirees with a
      higher prevalence of obesity. As a result, an equally dramatic future increase
      can be anticipated in the prevalence of age- and obesity-related disorders. The
      traditional paradigm of Japanese healthcare is not conducive to the restraint
      necessary for preserving its future viability, given these trends. Japanese
      healthcare does not reward clinical problem-solving skills, values specialists
      over generalists, places a heavy reliance on expensive technology, does not
      require interventions to be evidence-based, and provides no incentives to improve
      quality or efficiency. If this paradigm endures, Japanese healthcare faces the
      real prospect of bankruptcy. The failure of Japanese medical education to
      inculcate clinical skills and stress evidence-based medical practice lies at the
      heart of the impending crisis in healthcare. To solve the crisis, medical
      education in Japan must change its focus to training and developing a cadre of
      physicians with the broad-based expertise and clinical skills to make evidence
      based decisions in a medically and fiscally responsible manner. The future health
      of the system and of the Japanese people depends on it.

PMID- 17191069
TI  - Forensic aspects related to pediatric pathology--Medicolegal aspects of pediatric
      head injuries.
AB  - The pathological examination and assessment of inflicted head injuries in infants
      and young children are often complicated by the subtle nature of the injuries,
      the non-specificity of lesions, and the lack of experimental data that can be
      used to clarify possible forces and mechanisms of damage. Opinions often have to
      be given on a number of issues, with a paucity of information in the literature
      and lack of specific individual experience. The following paper reviews some of
      the problems that are currently found in the medicolegal evaluation of infants
      and young children with inflicted craniocerebral trauma and issues that
      consequently arise in court.

PMID- 17191070
TI  - Time course of cerebral blood flow changes following electroconvulsive therapy in
      depressive patients--measured at 3 time points using single photon emission
      computed tomography.
AB  - Although electroconvulsive therapy (ECT) has been employed for treating
      depression for more than 60 years, its mechanisms of action are yet unknown. To
      clarify the ECT effects on brain function, we examined cerebral blood flow (CBF)
      using single photon emission computed tomography at 3 time points--few days
      before an ECT course (Pre) and approximately 5 days (Post 1) and 1 month (Post 2)
      after the last ECT session. Eight depressive patients completed the study. In all
      the patients, the depressive symptoms improved after the ECT course, and major
      cognitive impairment was not observed at any time point. At Pre, the regional CBF
      (rCBF) in the widespread areas in the frontal lobe and limbic regions including
      cingulate cortex and parahippocampal gyrus was lower in the patients than in the
      normal controls. At Post 1 and Post 2, the rCBF in the frontal and limbic regions
      continued to be lower in the patients than in the controls although the
      successive recovery of decreased rCBF in the frontal region was observed.
      Regarding the time course among the patients, the rCBF in the right medial
      frontal region significantly increased (toward normal) at Post 2, not at Post 1.
      These findings suggest that depressive patients have decreased CBF in the frontal
      and limbic regions, and the medial frontal region plays a crucial role in ECT and
      recovery from depression. Further, patients who have undergone ECT treatment for
      depression should be carefully observed because brain functions continue to
      change even after a successful ECT course.

PMID- 17191071
TI  - Correction of the biochemical and functional deficits in fabry mice following
      AAV8-mediated hepatic expression of alpha-galactosidase A.
AB  - The advent of novel adeno-associated virus (AAV) serotype vectors with higher
      transduction activity has encouraged a re-evaluation of the merits of this
      delivery platform for a variety of diseases. We report here that administration
      of a recombinant AAV8-based serotype vector encoding human alpha-galactosidase A
      into Fabry mice facilitated more rapid and significantly higher levels of
      production of the enzyme than an AAV2 vector. This translated into improved
      clearance of globotriaosylceramide, the glycosphingolipid that accumulates in the
      lysosomes of affected Fabry cells, and to correction of the peripheral neuropathy
      shown associated with this disease. The higher levels of alpha-galactosidase A
      expression also allowed for a more rapid induction of immunotolerance to the
      enzyme. Recombinant AAV8 vectors that facilitated hepatic-restricted expression
      of high levels of alpha-galactosidase A conferred immunotolerance to the
      expressed enzyme as early as 30 days post-treatment. Animals expressing lower
      levels of the hydrolase, such as those treated with an AAV2-based vector or with
      lower doses of the AAV8-based vector, were also able to develop immunotolerance,
      but only after a more extended time period. Adoptive transfer of T cells isolated
      from the spleens of immunotolerized mice suppressed the formation of antibodies
      in naive recipient animals, suggesting the possible role of regulatory T cells in
      effecting this state.

PMID- 17191072
TI  - Targeting interferon-alpha increases antitumor efficacy and reduces
      hepatotoxicity of E1A-mutated spread-enhanced oncolytic adenovirus.
AB  - Novel approaches are needed to improve the antitumor potency and to increase the
      cancer specificity of oncolytic adenoviruses (Ad). We hypothesized that the
      combination of interferon-alpha (IFN-alpha) expression with a specific mutation
      in the e1a gene of Ad could target vector replication to genetic defects in the
      IFN-alpha pathway resulting in both improved antitumor efficacy and reduced
      toxicity. The conditionally replicative Ad vector KD3-IFN carries the dl1101/1107
      mutation in the e1a gene that eliminates binding of E1A proteins to p300/CBP and
      pRb. KD3-IFN expresses human IFN-alpha in concurrence with vector replication and
      overexpresses the adenovirus death protein (ADP; E3-11.6K). The antitumor
      activity of KD3-IFN was significantly higher than that of a control vector in
      established human hepatocellular carcinoma tumors in immunodeficient mice and in
      hamster kidney cancer tumors in immunocompetent Syrian hamsters. The dl1101/1107
      mutation rendered Ad replication sensitive to the antiviral effect of IFN-alpha
      in normal as opposed to cancer cells. These results translated to reduced vector
      toxicity upon systemic administration to C57BL/6 mice. The combination of Ad
      oncolysis, ADP overexpression, and IFN-alpha-mediated immunotherapy represents a
      three-pronged approach for increasing the anticancer efficacy of replicative Ads.
      Exploiting the dl1101/1107 mutation provides a mechanism for additional
      selectivity of IFN-alpha-expressing replication-competent Ads.

PMID- 17191073
TI  - Retroviral vectors encoding a reverse transcription-activated transgene
      efficiently limit expression of the gene to target cells.
AB  - Recombinant retroviral vectors are indispensable tools for the study of gene
      function and for therapeutic gene transfer owing to their ability to transfer and
      stably express foreign genes in target cells. A limitation of these vectors,
      however, is the difficulty in generating stable vector producer cell (VPC) lines
      when the vectors encode cytotoxic proteins. We developed a series of Moloney
      murine leukemia virus-based vectors encoding a reverse transcription-activated
      transgene. These vectors preclude gene expression in the producer cells, yet
      allow lines for transgene expression in target cells. The vectors were generated
      by cloning the gene of interest in reverse orientation either just upstream of
      the viral 3' long terminal repeat (LTR) or in the U3 region of the 3'LTR. An
      exogenous promoter was inserted, also in reverse orientation, at the R-U5 border
      of the viral 5'LTR. Upon transduction of target cells, the inserted promoter is
      copied to the 3'LTR during reverse transcription of the vector genomic RNA, where
      it then drives transgene expression. We tested this system using a green
      fluorescent protein (GFP) gene and the SV40 promoter. Reverse transcription
      activated retroviral vectors may allow for the generation of stable retroviral
      VPC lines encoding cytotoxic or inhibitory genes.

PMID- 17191075
TI  - The disease triangle: pathogens, the environment and society.
AB  - The primary means to define any disease is by naming a pathogen or agent that
      negatively affects the health of the host organism. Another assumed, but often
      overlooked, determinant of disease is the environment, which includes deleterious
      physical and social effects on mankind. The disease triangle is a conceptual
      model that shows the interactions between the environment, the host and an
      infectious (or abiotic) agent. This model can be used to predict epidemiological
      outcomes in plant health and public health, both in local and global communities.
      Here, the Irish potato famine of the mid-nineteenth century is used as an example
      to show how the disease triangle, originally devised to interpret plant disease
      outcomes, can be applied to public health. In parallel, malaria is used to
      discuss the role of the environment in disease transmission and control. In both
      examples, the disease triangle is used as a tool to discuss parameters that
      influence socioeconomic outcomes as a result of host-pathogen interactions
      involving plants and humans.

PMID- 17191074
TI  - H-NS, the genome sentinel.
AB  - Two recent reports have indicated that the H-NS protein in Salmonella enterica
      serovar Typhimurium has a key role in selectively silencing the transcription of
      large numbers of horizontally acquired AT-rich genes, including those that make
      up its major pathogenicity islands. Broadly similar conclusions have emerged from
      a study of H-NS binding to DNA in Escherichia coli. How do these findings affect
      our view of H-NS and its ability to influence bacterial evolution?

PMID- 17191076
TI  - Quantification of dopamine transporter binding using [18F]FP-beta-CIT and
      positron emission tomography.
AB  - The purpose of this study was to compare different kinetic and semi-quantitative
      methods for analysing human [18F]FP-beta-CIT studies: plasma input models,
      simplified (SRTM) and full (FRTM) reference tissue models, standard uptake values
      (SUV) and SUV ratios (SUVr). Both simulations and clinical evaluations were
      performed to determine the effects of noise, scan duration and blood volume on
      Akaike model selection, and on precision and accuracy of estimated parameters.
      For typical noise levels (COV approximately 2.5%) and scan durations (<90 mins),
      simulations provided poor fits (Akaike criterion) in case of reversible plasma
      input models showing a relatively high number of outliers compared with the two
      tissue irreversible model. Reference tissue models provided more reliable fits,
      which were nearly independent of noise and scan duration. For clinical data, two
      tissue irreversible and reversible plasma input models fitted striatum curves
      equally well (Akaike criterion). BP with plasma input models were less precise
      and contained more outliers than BP obtained with SRTM or FRTM. Among all methods
      tested, SRTM showed the highest contrast between patients and controls. When
      differentiating between patients and controls, SUVr performed almost equally well
      as SRTM, although contrast between striatum and background was lower. In
      conclusion, SRTM provided BP estimates with the highest precision and accuracy.
      Moreover, SRTM provided good contrast between patients and controls, and between
      striatum and background. SRTM is therefore the method of choice for quantitative
      [18F]FP-beta-CIT studies. SUVr might be an alternative for larger clinical
      trials.

PMID- 17191077
TI  - Blood-oxygen-level-dependent magnetic resonance signal and cerebral oxygenation
      responses to brain activation are enhanced by concurrent transient hypertension
      in rats.
AB  - Neuronal activation results in increases in blood-oxygen-level-dependent (BOLD)
      signal increases in magnetic resonance images, increases in cerebral blood flow
      (CBF), and changes in tissue oxygenation. We hypothesized that transient
      hypertension concurrent with neuronal activation would interfere with the normal
      physiological responses to neuronal activation potentially leading to additive
      responses. Anesthetized rats were prepared for functional magnetic resonance
      imaging studies in which increases in BOLD signal were measured in response to:
      (1) electrical forepaw stimulation, (2) different graded levels of transient
      hypertension produced with norepinephrine, and both 1 and 2. In other experiments
      with a similar protocol, changes in CBF and cortical oxyhemoglobin (oxyHb) and
      deoxyhemoglobin (deoxyHb) were measured using Laser Doppler Flowmetry and near
      infrared (IR) spectroscopy. BOLD signal within the sensory-motor cortex increased
      during forepaw stimulation. These matched increases in CBF and oxyHb and
      decreases in deoxyHb. During moderate or severe transient hypertension, there was
      a blood pressure-dependent increase in BOLD signal, CBF, and oxyHb; and a
      decrease in deoxyHb. When transient hypertension and forepaw stimulation were
      combined, the responses of oxyHb, deoxyHb, or BOLD signal were generally a
      summation of each response. In contrast, the CBF response to forepaw stimulation
      was relatively unaffected by transient hypertension. We conclude that during
      stimulation with concurrent hypertension, the normal changes in tissue
      oxygenation that accompany neuronal activation are enhanced by the increases
      produced by hypertension despite an excellent autoregulation of CBF. The latter
      could reflect highly transient decreases in oxygen consumption or likely a
      redistribution of flow through more nonexchange vessels.

PMID- 17191078
TI  - Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration
      after focal cerebral ischemia.
AB  - Transient focal ischemia is known to induce proliferation of neural progenitors
      in adult rodent brain. We presently report that doublecortin positive neuroblasts
      formed in the subventricular zone (SVZ) and the posterior peri-ventricle region
      migrate towards the cortical and striatal penumbra after transient middle
      cerebral artery occlusion (MCAO) in adult rodents. Cultured neural progenitor
      cells grafted into the non-infarcted area of the ipsilateral cortex migrated
      preferentially towards the infarct. As chemokines are known to induce cell
      migration, we investigated if monocyte chemoattractant protein-1 (MCP-1) has a
      role in post-ischemic neuroblast migration. Transient MCAO induced an increased
      expression of MCP-1 mRNA in the ipsilateral cortex and striatum. Immunostaining
      showed that the expression of MCP-1 was localized in the activated microglia and
      astrocytes present in the ischemic areas between days 1 and 3 of reperfusion.
      Furthermore, infusion of MCP-1 into the normal striatum induced neuroblast
      migration to the infusion site. The migrating neuroblasts expressed the MCP-1
      receptor CCR2. In knockout mice that lacked either MCP-1 or its receptor CCR2,
      there was a significant decrease in the number of migrating neuroblasts from the
      ipsilateral SVZ to the ischemic striatum. These results show that MCP-1 is one of
      the factors that attract the migration of newly formed neuroblasts from
      neurogenic regions to the damaged regions of brain after focal ischemia.

PMID- 17191079
TI  - Dihydropyridine calcium antagonists increase fibrinolytic activity: a systematic
      review.
AB  - Calcium antagonists have been shown to be superior over other antihypertensive
      drugs to prevent stroke. Because this cannot be fully attributed to blood
      pressure lowering effects, other mechanisms seem to play a role. Previously we
      found in patients with subarachnoid hemorrhage that nimodipine enhances
      fibrinolytic activity. The purpose of this systematic review was to investigate
      the fibrinolytic effect of calcium antagonists in general, especially in patients
      with hypertension. We systematically studied the entire PUBMED and EMBASE
      database with the search terms 'calcium antagonist' combined with 'fibrinolysis',
      '(euglobulin) clot lysis time' (ECLT), 'tissue plasminogen activator' (tPA), or
      'plasminogen activator inhibitor' (PAI). Twenty-six prospective studies were
      identified and 22 manuscripts were included (802 investigated individuals). The
      results show that calcium antagonists significantly increase fibrinolysis as
      shown by a reduction of the ECLT standardized mean differences (SMD) -0.58 (95%
      confidence interval (CI) -1.05 to -0.11)) and an increase of tPA activity (SMD
      0.73 (95% CI 0.25 to 1.21)). This increase of fibrinolysis is apparently caused
      by an increase of the tPA antigen level (SMD 0.16 (95% CI -0.05 to 0.37)) and a
      decrease of the plasminogen activator inhibitor-1 antigen antigen (SMD -0.36 (95%
      CI -0.74 to 0.02)). A sensitivity analysis showed that dihydropyridines, but not
      phenylalkylamines, exert a fibrinolytic effect. This fibrinolytic effect is not
      only seen in patients with subarachnoid hemorrhage but also in hypertensive
      patients. In conclusions, calcium antagonists increase fibrinolytic activity.
      This may add to the beneficial pharmacological effect of calcium antagonists to
      prevent ischemic events in patients with hypertension and subarachnoid
      hemorrhage.

PMID- 17191080
TI  - Sickle cell trait and gross hematuria.

PMID- 17191081
TI  - Urinalysis in Western culture: a brief history.
AB  - Today physicians use urine to diagnose selective conditions but from ancient
      times until the Victorian era, urine was used as the primary diagnostic tool.
      Laboratory medicine began with the analysis of human urine, which was called
      uroscopy and today is termed urinalysis. Uroscopy was the mirror of medicine for
      thousands of years. From a liquid window through which physicians felt they could
      view the body's inner workings. Numerous, somewhat accurate, physiologic theories
      arose from uroscopy. Then the importance of urinary diagnosis became exaggerated,
      and increasingly complex, until physicians required only the presence of urine,
      not patients, to diagnose disease. Uroscopy then escaped medical control,
      becoming first a home health aid and then a tool of uneducated practitioners.
      Thomas Brian led a medical rebellion against all uses of uroscopy and published
      the Pisse Prophet, a book that devastated uroscopy.

PMID- 17191082
TI  - Mitogen-activated protein kinase upregulation reduces renal D1 receptor affinity
      and G-protein coupling in obese rats.
AB  - Reactive oxygen species play a key role in pathophysiology of cardiovascular
      diseases by modulating G-protein-coupled receptor signaling. We have shown that
      treatment of animal models of diabetes and aging with tempol decreases oxidative
      stress and restores renal dopamine D1 receptor (D1R) function. In present study,
      we determined whether oxidation of D1R and upregulation of mitogen-activated
      protein kinases (MAPK) were responsible for decreased D1R signaling in obese
      animals. Male lean and obese Zucker rats were supplemented with antioxidants
      tempol or lipoic acid for 2 weeks. Compared to lean, obese animals were
      hyperglycemic and hyperinsulinemic with increased oxidative stress, D1R oxidation
      and decreased glutathione levels. These animals had decreased renal D1R affinity
      and basal coupling to G-proteins. SKF-38393, a D1R agonist failed to stimulate G
      proteins and adenylyl cyclase. Obese animals showed marked increase in renal MAPK
      activities. Treatment of obese rats with tempol or lipoic acid decreased blood
      glucose, reduced oxidative stress, and restored the basal D1R G-protein coupling.
      Antioxidants also normalized MAPK activities and restored D1R affinity and SKF
      38393 induced D1R G-protein coupling and adenylyl cyclase stimulation. These
      studies show that D1R oxidation and MAPK upregulation contribute to D1R
      dysfunction in obese animals. Consequently, antioxidants while reducing the
      oxidative stress normalize the MAPK activities and restore D1R signaling.

PMID- 17191083
TI  - Severity of tubulointerstitial inflammation and prognosis in immunoglobulin A
      nephropathy.
AB  - Many risk factors for progression in immunoglobulin A nephropathy (IgAN) have
      been found. We focused on renal leukocyte infiltrations and cytokines in IgAN.
      The subjects were 204 IgAN patients. Renal histopathological changes were
      semiquantitatively graded. Expression of tubulointerstitial Leukocyte common
      antigen (LCA), CD3, CD68, interleukin (IL)-1beta, and IL-10 was evaluated by
      immunohistochemistry. These parameters were correlated with progression of IgAN.
      The significance of these correlations was tested by a multivariate analysis.
      Glomerulosclerosis, tubular atrophy, interstitial inflammation, and hyaline
      arteriolosclerosis correlated with progression in all patients and also in
      patients with initially normal serum creatinine. Tubulointerstitial LCA, CD3,
      CD68, and IL-1beta expression correlated with progression. CD3 had the strongest
      correlation. In the multivariate analysis, tubulointerstitial CD3,
      hypertriglyceridemia, elevated serum creatinine concentration, and interstitial
      fibrosis were independently associated with progressive disease in all patients,
      and tubulointerstitial CD3 expression and hyaline arteriolosclerosis in patients
      with initially normal serum creatinine. We found parameters reflecting
      tubulointerstitial inflammation to predict deterioration of renal function in
      IgAN. This was also seen in patients whose serum creatinine was normal at the
      time of renal biopsy. Our findings show that, an immunohistochemical evaluation
      of tubulointerstitial inflammation seems to be a useful tool in determining the
      prognosis in IgAN.

PMID- 17191084
TI  - Phosphorus balance and mineral metabolism with 3 h daily hemodialysis.
AB  - Poor control of mineral metabolism is independently associated with mortality in
      patients receiving hemodialysis. We analyzed data from a 12-month, prospective,
      non-randomized, controlled study of daily hemodialysis (DHD) (six sessions/week 3
      h each) (n=26) vs conventional hemodialysis (CHD) (three sessions/week 4 h each)
      (n=51) for achievement of mineral metabolism goals and we performed a substudy of
      weekly dialytic phosphorus removal in DHD vs CHD. Phosphorus control was superior
      in the DHD group (% change from baseline to end-of-study -27+/-30% vs +7%+/-35%
      in the CHD group, P=0.0001). Percentage of patients using phosphate binders
      decreased from 77 to 40% among subjects on DHD, whereas these parameters did not
      change (76 vs 77%) in the CHD group (P=0.03 by Breslow-Day test for homogeneity
      of the odds ratios). Weekly mean phosphorus removal was higher in the DHD group
      (2452+/-720 mg/week vs 1572+/-366 mg/week, P=0.04). Mean normalized protein
      catabolic rate increased (0.90+/-0.43-1.22+/-0.26 g/kg/day, P=0.0013). DHD was
      also associated with an increase in the percent of subjects achieving three or
      more mineral metabolism goals (for phosphorus, calcium x phosphorus and
      parathyroid hormone) (15 vs 46%, P=0.046). In conclusion, DHD improves phosphorus
      control by increasing dialytic phosphorus removal while maintaining nutritional
      status and reducing the use of phosphate binders. The net effect allows for
      improved achievement of mineral metabolism goals.

PMID- 17191085
TI  - Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of
      peritoneal sclerosis in a mouse experimental model.
AB  - Peritoneal sclerosis is a major and serious complication in patients on long-term
      continuous ambulatory peritoneal dialysis (PD). The involvement of angiogenesis
      and proangiogenic factors such as vascular endothelial growth factor (VEGF)-A in
      progressing peritoneal sclerosis has been reported. We previously reported the
      therapeutic efficacy of endostatin peptide, a potent inhibitor of angiogenesis
      derived from type XVIII collagen, in a mouse diabetic nephropathy model. Here, we
      examined the therapeutic effect of endostatin peptide in preventing progression
      in a mouse peritoneal sclerosis model. Male ICR mice received intraperitoneal
      injections of chlorhexidine gluconate (CG) every other day to induce peritoneal
      sclerosis. Endostatin peptide (1 or 4 mg/kg/day) was administered via
      subcutaneously implanted osmotic minipumps. Peritoneal sclerosis (day 24) was
      significantly suppressed by endostatin peptide in a dose-dependent manner.
      Peritoneal accumulation of type III collagen was significantly suppressed by
      endostatin peptide. Increase in the number of CD31(+) blood vessels, F4/80(+)
      monocyte/macrophage accumulation, and 5-bromodeoxyuridine(+) proliferating cells
      was significantly inhibited by endostatin peptide. Increase in peritoneal
      expression of VEGF-A, profibrotic transforming growth factor-beta1, and alpha
      smooth muscle actin was suppressed by endostatin peptide. Immunoreactivity for
      endogenous endostatin (whole molecule) and endostatin receptor alpha5beta1
      integrin was increased and colocalized to CD31(+) blood vessels in the thickened
      peritonea of CG-injected mice. These results demonstrate the potential use of
      antiangiogenic endostatin peptide as a novel therapeutic agent in preventing
      peritoneal sclerosis, a severe complication in patients undergoing long-term PD.

PMID- 17191086
TI  - A detergent-based assay for the detection of promiscuous inhibitors.
AB  - At micromolar concentrations, many small molecules self-associate into colloidal
      aggregates that non-specifically inhibit enzymes and other proteins. Here we
      describe a protocol for identifying aggregate-based inhibitors and distinguishing
      them from small molecules that inhibit via specific mechanisms. As a convenient
      proxy for promiscuous, aggregate-based inhibition, we monitor inhibition of beta
      lactamase in the absence and presence of detergent. Inhibition that is attenuated
      in the presence of detergent is characteristic of an aggregate-based mechanism.
      In the 96-well-format assay described here, about 200 molecules can be tested, in
      duplicate, per hour for detergent-dependent sensitivity. Furthermore, we also
      describe simple experiments that can offer additional confirmation of aggregate
      based inhibition.

PMID- 17191089
TI  - Recreational Viagra Use and Sexual Risk among Drug Abusing Men.
AB  - Until recently, the Viagra connection to HIV was anchored in older adults.
      However, CDC investigation showed stability in 50+ HIV diagnoses on the heels of
      upward trends in risk indicators among men who have sex with men (MSM) and
      substance abusing populations. Signs have increasingly pointed to recreational
      drug use among younger populations, to which Viagra is being added to the mix.
      Currently, the field is still locating the substance abuse, sexual risk and age
      related dimensions of Viagra misuse. Recent studies identify it primarily as
      substance abuse, but the majority reports a combination of risky sex and risky
      drug use. At the very least, Viagra appears related to the enhancement of sexual
      experience or performance, even when it is used to compensate for erectile
      dysfunction caused by other drugs-either illicit or prescribed (e.g.,
      antidepressants and highly active antiretroviral therapy or HAART). The
      populations studied, however, frequently have limited the generalizability of
      findings. This report analyzes the relationship among Viagra, Club Drugs and HIV
      sexual risk behavior in drug using men with a sample diverse in sexual
      orientation and demographic scope. Participants were 640 males recruited from
      three HIV prevention programs in Los Angeles County. Mean age was 43.97 years,
      ranging from 18.7 to 70.3 with almost 25% over 50. Sexual orientation was 79%
      heterosexual, 8% bisexual and 12% gay. Racial composition was 45% white, 35%
      black and 19% Hispanic. NIDA's Risk Behavior Assessment and a Club Drug/Viagra
      addendum were used to collect socio-demographic, substance use and sexual risk
      data. Multiple logistic regression models were constructed along with chi-square
      tests of association and some t-tests. White race was a major risk factor. No age
      effect was found. MSM were more likely to use Viagra. Insertive anal sex was a
      significant co-factor among heterosexual Viagra users involved in transactional
      sex with women. In the overall sample and the subsets of heterosexual, MSM,
      younger and older men, predictive models all identified club or designer drugs as
      significant co-factors in the use of Viagra. Different patterns of drug co
      factors were observed for each subset. We detected consistent positive
      associations between the use of Viagra and the use of amphetamines immediately
      before or during sex. Viagra use has moved into a new generational context and
      now complicates the sexual risk and intervention equations for all men,
      particularly MSM as well as more hidden subgroups.

PMID- 17191090
TI  - Association between polymorphisms of biotransformation and DNA-repair genes and
      risk of colorectal cancer in Taiwan.
AB  - The relationship between diet and colorectal cancer has been previously
      demonstrated and supported with strong epidemiological evidence. The role of
      genetic polymorphisms has, however, been less well elaborated upon. We conducted
      a hospital-based case-control study including 727 cases and 736 healthy controls
      to evaluate the associations of the polymorphic phase-I and -II
      biotransformations (CYP1A1, CYP1A2, GSTM1, GSTT1, GSTP1, NAT1 and NAT2) and DNA
      repair enzymes (XRCC1, XRCC3 and XPD) with the risk of contracting colorectal
      cancer. We found that men featuring the CYP1A1*2C G/G genotype, the GSTT1 null
      genotype and XPD 751 with the Gln allele were associated with an elevated risk of
      colorectal cancer than were men who did not exhibit such genetic features.
      Multivariate logistic regression analysis revealed that individuals featuring
      more than two high-risk genotypes increased the colorectal-cancer risk 3.1-fold
      (OR = 3.1, 95% CI = 1.8-5.2). For women, subjects featuring the CYP1A1*2C G/G
      genotype and the XRCC3 Thr/Thr genotype faced a 3.1-fold greater risk (95% CI =
      1.3-7.0) of colorectal cancer when compared to those featuring the CYP1A1*2C A
      allele and the XRCC3 Met allele. Taken together, this study suggests that
      polymorphisms of genes involved in biotransformation and DNA repair could
      modulate colorectal-cancer risk in Taiwan.

PMID- 17191091
TI  - Vehicle effects on the in vitro penetration of testosterone through equine skin.
AB  - The effects of three vehicles, phosphate-buffered saline (PBS), ethanol (50% in
      PBS w/w) and propylene glycol (50% in PBS w/w) on in vitro transdermal
      penetration of testosterone was investigated in the horse. Skin was harvested
      from the thorax of five Thoroughbred horses after euthanasia and stored at -20
      degrees C until required. The skin was then defrosted and placed into Franz-type
      diffusion cells, which were maintained at approximately 32 degrees C by a water
      bath. Saturated solutions of testosterone, containing trace amounts of
      radiolabelled [14C]testosterone, in each vehicle were applied to the outer
      (stratum corneum) surface of each skin sample and aliquots of receptor fluid were
      collected at 0, 2, 4, 8, 16, 20, 22 and 24 h and analysed for testosterone by
      scintillation counting. The maximum flux (Jmax) of testosterone was significantly
      higher for all sites when testosterone was dissolved in a vehicle containing 50%
      ethanol or 50% propylene glycol, compared to PBS. In contrast, higher residues of
      testosterone were found remaining within the skin when PBS was used as a vehicle.
      This study shows that variability in clinical response to testosterone could be
      expected with formulation design.

PMID- 17191092
TI  - Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and
      maturation.
AB  - PURPOSE: Biological mechanisms of tissue regeneration are often complex,
      involving the tightly coordinated spatial and temporal presentation of multiple
      factors. We investigated whether spatially compartmentalized and sequential
      delivery of factors can be used to pattern new blood vessel formation. MATERIALS
      AND METHODS: A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system
      was used to locally present vascular endothelial growth factor (VEGF) alone in
      one spatial region, and sequentially deliver VEGF and platelet-derived growth
      factor (PDGF) in an adjacent region. Scaffolds were implanted in severely
      ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was
      quantified within the scaffolds. RESULTS: In the compartment delivering a high
      dose of VEGF alone, a high density of small, immature blood vessels was observed
      at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood
      vessel density, but vessel size and maturity were significantly enhanced. Results
      were similar at 6 weeks, with continued remodeling of vessels in the VEGF and
      PDGF layer towards increased size and maturation. CONCLUSIONS: Spatially
      localizing and temporally controlling growth factor presentation for angiogenesis
      can create spatially organized tissues.

PMID- 17191093
TI  - Skin irritation in transdermal drug delivery systems: a strategy for its
      reduction.
AB  - PURPOSE: Active pharmaceutical ingredients (API) in transdermal drug delivery
      systems (TDS) often causes skin irritation such as erythema and edema. We have
      studied a possible approach for the reduction of skin irritation by patch
      formulations that control the rates of skin permeation and elimination of API.
      METHODS: Loxoprofen (LX-base) was used to induce the skin irritation. The redness
      value (Deltaa) was evaluated as a measure of erythema by Chroma Meter. The in
      vitro skin permeation and release profiles were also investigated by using a side
      by-side diffusion cell. RESULTS: The redness values were not correlated either
      with the cumulative amount of API permeated or the concentration of LX-base in
      the skin, but well correlated with the elimination rate of LX-base from the skin
      after the removal of the formulation. The formulation with gradual decrease of
      permeation rate during application accelerated the elimination rate after
      application, and resulted in the reduction of the skin irritation. CONCLUSIONS:
      The skin pharmacokinetics of API, not only permeation during application but also
      release after the patch removal, was found to be a significant factor for skin
      irritation. To minimize the skin irritation, it's also important to eliminate the
      residual API in the skin promptly after application.

PMID- 17191095
TI  - Kinetic considerations for the quantitative assessment of efflux activity and
      inhibition: implications for understanding and predicting the effects of efflux
      inhibition.
AB  - PURPOSE: Unexpected and complex experimental observations related to efflux
      transport have been reported in the literature. This work was conducted to
      develop relationships for efflux activity (PS(efflux)) as a function of commonly
      studied kinetic parameters [permeability-surface area product (PS), efflux ratio
      (ER), degree of efflux inhibition (phi(i)), 50% inhibitory concentration
      (IC(50)), and Michaelis-Menten constant (K(m))]. METHODS: A three-compartment
      model (apical, cellular, and basolateral) was used to derive flux equations
      relating the initial rate of flux and steady-state mass transfer in the presence
      or absence of active efflux. Various definitions of efflux ratio (ER) were
      examined in terms of permeability-surface area products. The efflux activity
      (PS(efflux)) was expressed in terms of ER and PS. The relationships between
      PS(efflux) and PS, ER, phi(i), IC(50), and K(m) were solved mathematically.
      Simulations and examples from the literature were used to illustrate the
      resulting mathematical relationships. RESULTS: The relationships derived
      according to a three-compartment model differed fundamentally from commonly
      accepted approaches for determining PS(efflux), phi(i), IC(50) and K(m). Based on
      the model assumptions and mathematical derivations, currently used mathematical
      relationships erroneously imply that efflux activity is proportional to change in
      PS (i.e., flux or P(app)) and thus underestimate PS(efflux) and phi(i,) and
      overestimate IC(50) and K(m). CONCLUSIONS: An understanding of the relationship
      between efflux inhibition and kinetic parameters is critical for appropriate data
      interpretation, standardization in calculating and expressing the influence of
      efflux transport, and predicting the clinical significance of efflux inhibition.

PMID- 17191094
TI  - Particle size analysis in pharmaceutics: principles, methods and applications.
AB  - Physicochemical and biopharmaceutical properties of drug substances and dosage
      forms can be highly affected by the particle size, a critical process parameter
      in pharmaceutical production. The fundamental issue with particle size analysis
      is the variety of equivalent particle diameters generated by different methods,
      which is largely ascribable to the particle shape and particle dispersion
      mechanism involved. Thus, to enable selection of the most appropriate or optimal
      sizing technique, cross-correlation between different techniques may be required.
      This review offers an in-depth discussion on particle size analysis pertaining to
      specific pharmaceutical applications and regulatory aspects, fundamental
      principles and terminology, instrumentation types, data presentation and
      interpretation, in-line and process analytical technology. For illustration
      purposes, special consideration is given to the analysis of aerosols using time
      of-flight and cascade impactor measurements, which is supported by a
      computational analysis conducted for this review.

PMID- 17191096
TI  - Visual Fixation Patterns during Reciprocal Social Interaction Distinguish a
      Subgroup of 6-Month-Old Infants At-Risk for Autism from Comparison Infants.
AB  - Thirty-one infant siblings of children with autism and 24 comparison infants were
      tested at 6 months of age during social interaction with a caregiver, using a
      modified Still Face paradigm conducted via a closed-circuit TV-video system. In
      the Still Face paradigm, the mother interacts with the infant, then freezes and
      displays a neutral, expressionless face, then resumes interaction. Eye tracking
      data on infant visual fixation patterns were recorded during the three episodes
      of the experiment. Using a hierarchical cluster analysis, we identified a
      subgroup of infants demonstrating diminished gaze to the mother's eyes relative
      to her mouth during the Still Face episode. Ten out of the 11 infants in this
      subgroup had an older sibling with autism.

PMID- 17191098
TI  - Network model of decreased context utilization in autism spectrum disorder.
AB  - Individuals with autism spectrum disorders (ASD) demonstrate impaired utilization
      of context, which allows for superior performance on the "false memory" task. We
      report the application of a simplified parallel distributed processing model of
      context utilization to the false memory task. For individuals without ASD,
      experiments support a model wherein presentation of one word, e.g., ''apple,''
      strongly activates the neighboring nodes of closely related words such as
      ''fruit,'' ''tree,'' whereas in ASD these neighboring nodes are relatively less
      activated. We demonstrate this model to be consistent with the superior
      performance on recognition testing on the false memory test, but not on free
      recall. This may have an anatomic basis in diminished hippocampal neuronal
      arborization and the abnormal minicolumnar pathology in ASD.

PMID- 17191097
TI  - Variation in vocal-motor development in infant siblings of children with autism.
AB  - In this study we examined early motor, vocal, and communicative development in a
      group of younger siblings of children diagnosed with autism (Infant Siblings).
      Infant Siblings and no-risk comparison later-born infants were videotaped at home
      with a primary caregiver each month from 5 to 14 months, with follow-up at 18
      months. As a group, Infant Siblings were delayed in the onset of early
      developmental milestones and spent significantly less time in a greater number of
      postures, suggestive of relative postural instability. In addition, they
      demonstrated attenuated patterns of change in rhythmic arm activity around the
      time of reduplicated babble onset; and they were highly likely to exhibit delayed
      language development at 18 months.

PMID- 17191099
TI  - Pseudonymization of radiology data for research purposes.
AB  - Medical image processing methods and algorithms, developed by researchers, need
      to be validated and tested. Test data would ideally be real clinical data
      especially that clinical data is varied and exists in large volumes. Nowadays,
      clinical data is accessible electronically and has important value for
      researchers. However, the usage of clinical data for research purposes should
      respect data confidentiality, patient right to privacy, and patient consent. In
      fact, clinical data is nominative given that it contains information about the
      patient such as name, age, and identification number. Evidently, clinical data
      needs to be de-identified to be exported to research databases. However, the same
      patient is usually followed during a long period of time. The disease progression
      and the diagnostic evolution represent extremely valuable information for
      researchers as well. Our objective is to build a research database from de
      identified clinical data while enabling the data set to be easily incremented by
      exporting new pseudonymous data, acquired over a long period of time.
      Pseudonymization is data de-identification, such that data belonging to an
      individual in the clinical environment still belong to the same individual in the
      de-identified research version. In this paper, we explore various software
      architectures to enable the implementation of an imaging research database that
      can be incremented in time. We also evaluate their security and discuss their
      security pitfalls. As most imaging data accessible electronically is available
      with the digital imaging and communication in medicine (DICOM) standard, we
      propose a de-identification scheme that closely follows DICOM recommendations.
      Our work can be used to enable electronic health record (EHR) secondary usage
      such as public surveillance and research, while maintaining patient
      confidentiality.

PMID- 17191100
TI  - An ROC study of chest radiographs: 2K Versus 4K high-resolution soft-copy images.
AB  - Computed radiography of chest with a 4K image array was recently introduced. We
      performed a multiobserver study to compare the diagnostic accuracy of 2K
      (standard) and 4K (high quality) chest radiographs displayed on a 5-mega-pixel
      monitor (2K monitor). One hundred cases of posteroanterior chest radiographs (a
      total of 200 images) were selected by two chest radiologists. Those radiographs
      included pneumothorax (n = 14), nodules (n = 15), interstitial disease (n = 10),
      or neither abnormality (n = 61). These were interpreted by four radiologists in
      two separate sessions. They recorded their confidence scale for the presence or
      absence of abnormality. Diagnostic accuracy was determined by receiver operating
      characteristic (ROC) analysis for each observer. ROC analysis showed no
      statistically significant difference between the 2K and 4K modes for the
      detection of any of the different abnormalities by individual readers. Our
      preliminary study suggests that 2K mode would be sufficient for the detection of
      abnormality on chest radiograph and there is no considerable validity to incline
      toward the 4K mode in current picture archiving and communication system
      environment using 2K monitor. However, we think that additional investigation
      using more subtle parenchymal or rib lesion should be followed.

PMID- 17191101
TI  - The impact of PACS on radiologists' work practice.
AB  - This paper identifies and analyzes how the implementation and use of picture
      archiving and communication system impacts radiologists' work practice. The study
      is longitudinal from 1999 to 2005 and have a qualitative perspective were data
      were collected by structured interviews in a total of 46. The interviews were
      transcribed, analyzed, and coded using grounded theory as an organizing
      principle. In radiologists' work practice, three main categories were defined:
      professional role, diagnostic practice, and technology in use. The changing
      trends within the professional role indicated that radiologists moved from a more
      individual professional expertise to become more of an actor in a network. The
      diagnostic practice changed, as reading x-ray films was seen as an art form in
      1999, requiring years of training. Once everyone could view digital images,
      including 3-dimensional technology, it was easier for other clinicians to see and
      interpret the images and the skills become accessible to everyone. The change in
      technology in use as a result of the shift to digital images led to an increased
      specialization of the radiologist.

PMID- 17191102
TI  - 'Wet Reads' in the age of PACS: technical and workflow considerations for a
      preliminary report system.
AB  - Communication between clinicians, technologists, and radiologists has become more
      complex, with Picture Archiving and Communication Systems (PACS) now allowing the
      radiologist to be removed from the physical location of the patients and the site
      of imaging. With these changes, effective communication becomes an ongoing
      challenge. Efficient communication of study interpretations has also become a
      priority for radiologists as they struggle to maintain relevance and provide
      added value to patient care when clinicians have ready access to radiology
      images. The purpose of this paper is to share our experience in developing and
      implementing the Collaborative Notification System (CNS), a communication tool
      used to inform referring clinicians of urgent findings-a.k.a. "wet reads." The
      system utilizes a system of web pages integrated into PACS for the sending and
      receiving of succinct messages to provide clinical information at the point of
      need. A second system of pager alerts provides notification of the need for such
      communication through a relatively unintrusive, one-way, acknowledged alert
      system. The CNS provides asynchronous, integrated communication for the reporting
      of urgent and emergent radiology findings in a complex, geographically
      distributed medical environment.

PMID- 17191104
TI  - An integrated approach to a teaching file linked to PACS.
AB  - To meet the educational needs of a medical imaging department with a strong
      teaching commitment, a teaching file that uses digital data supplied by the
      institutional picture archiving and communications system (PACS) was required.
      This teaching file had to be easily used by the end users, have a simple
      submission process, be able to support multiple users, be searchable on all data
      fields, and implementing the teaching file must not incur any additional software
      or hardware costs. The teaching file developed to address this problem takes
      advantage of the database structure and capabilities of several components
      included in the commercial PACS installed at the hospital. MS Access is used to
      seamlessly integrate with the digital imaging and communication in medicine
      (DICOM) database of a normal work station that is part of the PACS. This
      integration allows relevant patient and study demographics to be copied from
      images of interest and then to be stored in a separate database as the back-end
      of the digital teaching file. When images for a particular teaching file case
      need to be reviewed, they are automatically retrieved and displayed from the main
      PACS database using an open application programming interface (API) connection
      defined on the PACS web server. Utilizing this open API connection means the
      teaching file contains only the relevant demographic information of each teaching
      file case; no image data is stored locally. The open API connection allows access
      to imaging data usually not encountered in a teaching file, allowing more
      comprehensive imaging case files to be developed by the radiologist. Other
      advantages of this teaching file design are that it does not duplicate image
      data, it is small allowing simple ongoing backup, and it can be opened with
      multiple users accessing the database without compromising data access or
      integrity.

PMID- 17191103
TI  - A comparative study of conventional mammography film interpretations with soft
      copy readings of the same examinations.
AB  - An acceptable mammography film digitizer must provide high-quality images at a
      level of diagnostic accuracy comparable to reading conventional film
      examinations. The purpose of this study was to determine if there are significant
      differences between the interpretations of conventional film-screen mammography
      examinations and soft copy readings of the images produced by a mammography film
      digitizer. Eight radiologists interpreted 120 mammography examinations, half as
      original films and the other half as digital images on a soft copy work station.
      No radiologist read the same examination twice. The interpretations were recorded
      in accordance with the Breast Imaging Reporting and Data System and included
      other variables such as perceived image quality and diagnostic difficulty and
      confidence. The results provide support for the hypothesis that there are no
      significant differences between the interpretations of conventional film-screen
      mammography examinations and soft copy examinations produced by a mammography
      film digitizer.

PMID- 17191105
TI  - Stephen Paget and the 'seed and soil' theory of metastatic dissemination.
AB  - The outcome of cancer metastasis depends on multiple interactions between
      selected metastatic cells and homeostatic mechanisms unique to some organ
      microenvironments. The English surgeon Stephen Paget (1855-1926) is credited with
      being the first to postulate the important role played by microenvironment in
      metastasis formation. The concept of his 'seed and soil' theory has been
      supported and confirmed by numerous publications. This review article summarises
      the most important literature data about this matter.

PMID- 17191106
TI  - Inhibitory effect of quercetin on tryptase and interleukin-6 release, and
      histidine decarboxylase mRNA transcription by human mast cell-1 cell line.
AB  - Mast cells are involved in inflammatory processes and in allergic reactions where
      immunologic stimulation leads to degranulation and generation of numerous
      cytokines and inflammatory mediators. Mast cells have been proposed as an immune
      gate to the brain, as well as sensors of environmental and emotional stress, and
      are likely involved in neuropathologic processes such as multiple sclerosis.
      Among mast cell products, the protease tryptase could be associated with
      neurodegenerative processes through the activation of specific receptors (PARs)
      expressed in the brain, while interleukin (IL)-6 likely causes neurodegeneration
      and exacerbates dysfunction induced by other cytokines; or it could have a
      protective effect against demyelinisation. In this report we show that quercetin,
      a natural compound able to act as an inhibitor of mast cell secretion, causes a
      decrease in the release of tryptase and IL-6 and the down-regulation of histidine
      decarboxylase (HDC) mRNA from human mast cell (HMC)-1 cells. As quercetin
      dramatically inhibits mast cell tryptase and IL-6 release and HDC mRNA
      transcription by HMC-1 cell line, these results nominate quercetin as a
      therapeutical compound in association with other therapeutical molecules for
      neurological diseases mediated by mast cell degranulation.

PMID- 17191107
TI  - Gene expression profile study in CFTR mutated bronchial cell lines.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic
      fibrosis conductance transmembrane regulator (CFTR). Symptoms are pancreatic
      insufficiency, chronic obstructive lung disease, liver disease, chronic sinusitis
      and infertility in male patients. The phenotypic variability may be explained
      only in part by the more than 1200 CFTR mutations, which are grouped into six
      different classes, according to their effect on the protein ranging from a severe
      (no synthesis or blocked processing) to mild mutation (altered conductance or
      reduced synthesis). However, it is now accepted that other genes (CF modifiers)
      influence the phenotypic spectrum of the disease. In order to identify CF
      modifier genes, we built a low-density home-made oligoarray containing 144 genes
      selected according to biochemical criteria and evaluated their expression in two
      CF bronchial epithelial cell lines (CuFi1 F508del/F508del; CuFi3 F508del/R553X).
      If we consider both cell lines, 38 genes (26.3%) show an altered expression
      pattern with a threshold > +/-1.5. Of these 38 genes, 12 are altered in CuFi1,
      and 26 in CuFi3. Some of these genes share the same expression pattern in both
      cell lines, while others have a different behaviour. These results were validated
      by a QRT-PCR assay (R2 CuFi1 = 0.81 and R2 CuFi3 = 0.91). These data could
      suggest that the presence of a class I allele (R553X) determines a more profound
      alteration of gene expression pattern than the presence of a class II allele
      (F508del). The identification of the genes altered by a specific CF mutation
      could lead to the development of a pharmacological approach specific for
      different CFTR genotypes.

PMID- 17191108
TI  - Investigation of chromosome 21 aneuploidies in breast fibroadenomas by
      fluorescence in situ hybridisation.
AB  - Fibroadenoma (FA) is a benign breast tumour that occurs in about 25% of women.
      Cytogenetic studies suggest that numerical chromosomal aberrations may contribute
      to tumorigenesis, but chromosomal instability is still poorly characterised in
      breast cancer. The aim of this study was to investigate numerical alterations of
      chromosome 21 in 15 breast FAs. All samples were analysed by classical
      cytogenetics and by fluorescence in situ hybridisation (FISH) for chromosome 21
      DNA sequences. Classical cytogenetics analysis showed that all cells were
      diploidies with modal number varying between 43 and 47 chromosomes, and clonal
      chromosome alterations in 46.7% of tumours. Clonal numerical alterations
      involved, preferentially, chromosomes 8, 10, 12, 16 and 21. FISH analysis showed
      a statistically significant difference for chromosome 21 monosomy between seven
      samples and control group. This monosomy varied from 24.5% to 43.5% of analysed
      cells. The presence of chromosomal alterations in FAs may be a consequence of the
      proliferation process and is probably not related to the aetiology of this type
      of lesion. The study of benign proliferations and comparison with chromosome
      alterations in their malignant counterparts should result in an understanding of
      the genes acting in cell proliferation alone and those that cause these cells to
      both undergo malignant transformation and become invasive.

PMID- 17191110
TI  - Alkaline comet assay study with breast cancer patients: evaluation of baseline
      and chemotherapy-induced DNA damage in non-target cells.
AB  - The sensitivity of the alkaline comet assay for the evaluation of baseline and
      treatment-induced DNA damage in white blood cells of breast cancer patients
      receiving adjuvant chemotherapy according to three conventional anthracycline-
      and cyclophosphamide-containing protocols was investigated. Additionally,
      baseline DNA damage in cancer patients was compared with the levels of DNA damage
      recorded in healthy women. Altogether 30 patients with diagnosed breast cancer
      and 30 female blood donors with no known familial history of breast cancer
      participated in the study. Alkaline comet assay was performed according to
      standard protocol and DNA migration in peripheral blood leukocytes was measured
      by a computer-based image analysis system. For each subject the frequency of
      "damaged" cells, i.e., long-tailed nuclei (LTN) with tail length exceeding 95th
      percentile for the considered parameter among controls, is also reported. Breast
      cancer patients had significantly increased background levels of DNA damage in
      their peripheral blood leukocytes as compared to healthy women. Prior to the
      chemotherapy, a majority of patients showed a statistically significant increase
      in the number of LTN compared to healthy blood donors. Marked interindividual
      variations in baseline DNA damage among patients were recorded, some of them
      related to the disease stage and status. The present study confirmed the alkaline
      comet assay as a sensitive technique able to detect significantly elevated DNA
      migration in blood cells of patients already one hour after completion of the
      first cycle of chemotherapy. Administration of antineoplastic drugs in three
      chemotherapy protocols studied induced a similar increase of primary DNA damage
      in nontarget cells. The evaluation of the LTN frequencies indicates the best
      response to the protocol containing cyclophosphamide, methotrexate and 5
      fluorouracil (CMF). Our results point to the significance of simultaneous
      evaluation of DNA migration and frequency of LTN in the same subject and approved
      the use of alkaline comet assay as a suitable method for the routine detection of
      critical DNA lesions produced after administration of antineoplastic drugs in the
      clinical settings.

PMID- 17191109
TI  - Imbalance of mononuclear cell infiltrates in the placental tissue from foetuses
      after spontaneous abortion versus therapeutic termination from 8th to 12th weeks
      of gestational age.
AB  - Placental macrophages (Hofbauer cells) are located close to trophoblastic cells
      and foetal capillaries, which make them perfect candidates for involvement in
      regulatory processes within the villous core. Their capacity of producing several
      cytokines and prostaglandin-synthesising enzymes, and expressing vascular
      endothelial growth factor, indicate a possible role in placental development and
      angiogenesis in order to support pregnancy. Common cells to Hofbauer macrophages
      sharing similar cell surface markers (HLA-A, -B, -C and leukocyte common antigen)
      have been reported in the stroma, decidua and amnion, indicating additional
      foetal protection. Yet this is not always the case. Most spontaneous abortions
      occur before 12 weeks' gestation, and most are due to chromosomal errors in the
      conceptus. Relatively few truly spontaneous abortions take place between 12 and
      20 weeks' gestation. Thereafter, between 20 and 30 weeks, another type of
      premature spontaneous termination becomes prevalent, which is due to ascending
      infection. The numbers of cells expressing the various markers of the
      monocytemacrophage lineage change throughout pregnancy. In the present study, we
      investigated the immunohistochemical expression of mononuclear infiltrations in
      paraffin-embedded placentas, from foetuses after spontaneous abortion (8th, 10th
      and 12th weeks of gestational age), and those after therapeutic abortion at the
      same time, using a panel of monoclonal antibodies for the identification of
      leukocytes (CD45/LCA), B-lymphocytes (CD20/L-26), T lymphocytes (CD45RO/UCHL1),
      CD68 and CD14 cells. Immunologic factors in human reproductive failure are
      plausible mechanisms of infertility and spontaneous abortion. Approximately 25%
      of cases of premature ovarian failure appear to result from an autoimmune
      aetiology. Unfortunately, current therapeutic options for these women are limited
      to exogenous hormone or gamete substitution. Local inflammations at the sites of
      endometriosis implants are postulated to mediate the pain and reduced
      fecundability associated with this clinical syndrome. The recruitment of immune
      cells, particularly monocytes and T-cells, neovascularisation around foci of
      invading peritoneal lesions, and the possible development of antiendometrial
      autoantibodies support an immunologic basis of this disorder. To date, treatment
      of pain and infertility associated with endometriosis is primarily surgical,
      although immune-based adjuvants are theoretical possibilities for the future.
      Finally, although hypotheses supporting immunologic mechanisms of recurrent
      pregnancy loss have been popular over the past decade, most clinical
      investigations in this area do not provide compelling evidence for this position.
      Reputable specialists in reproductive medicine use experimental immunotherapies
      judiciously in selected cases of repetitive abortion. For example, the use of
      anticoagulation therapy can be beneficial in cases with documented
      antiphospholipid antibodies. At present, however, efficacious immunotherapy
      protocols for general application have not been established. Despite these
      caveats, continued strides in our understanding of human reproductive immunology
      should yield considerable future progress in this field. During the physiological
      changes that occur in the first and in the beginning of the second trimester of
      pregnancy, spiral arteries of the placental bed are converted into the
      uteroplacental arteries. The essence of this conversion consists of losing the
      muscular elements in the vessel walls, making them unable to respond to vasomotor
      influences. Cells that infiltrate the walls of spiral arteries and replace their
      normal elements are called migratory, non-villous or intermediate trophoblastic
      cells. Besides infiltrating and replacing the anatomic structures of spiral
      arteries, intermediate trophoblastic cells also penetrate into the lumina of
      these vessels forming endovascular plugs. These plugs are one of the reasons why
      early uteroplacental blood flow cannot be visualised, even with transvaginal
      ultrasound, during the first 12 weeks of gestation. In uncomplicated pregnancies,
      the endovascular trophoblast is bound to disappear by the end of the second
      trimester of pregnancy, but the literature on this topic is scarce. Here we
      describe the detection, isolation and characterisation of CD45RO-, L26- and
      CD68/CD14-positive cells from human early pregnancy deciduas. These cells were
      found in close vicinity to endometrial glands, with preference to the basal layer
      of the decidua. We conclude that (1) maternal cells, apparently CD45RO/UCHL1
      positive cells, cross the maternofoetal barrier and participate in spontaneous
      (involuntary) abortions, and (2) a small proportion of maternal cells
      (approximately 30%), apparently CD68/CD14-positive cells, also cross the maternal
      foetal barrier and cause growth delay and recurrent reproductive failure. Further
      investigation of involvement of the intercellular adhesion molecules 1 and 2,
      platelet endothelial cell adhesion molecule, vascular cell adhesion molecule and
      E-selectin in leukocyte accumulation will be needed to support the passage of
      maternal cells to the foetus. The results were statistically significant
      (P<0.0001, Student's t-test).

PMID- 17191111
TI  - Atorvastatin decreases serum levels of advanced glycation end products (AGEs) in
      patients with type 2 diabetes.

PMID- 17191112
TI  - Regulation of differential pro- and anti-apoptotic signaling by glucocorticoids.
AB  - More than a quarter of a century ago, the phenomenon of glucocorticoid-induced
      apoptosis in the majority of hematological cells was first recognized. More
      recently, glucocorticoid-induced antiapoptotic signaling associated with
      apoptosis resistance has been identified in cells of epithelial origin, most of
      malignant solid tumors and some other tissues. Despite these huge amount of data
      demonstrating differential pro- and anti-apoptotic effects of glucocorticoids,
      the underlying mechanisms of cell type specific glucocorticoid signaling are just
      beginning to be described. This review summarizes our present understanding of
      cell type-specific pro- and anti-apoptotic signaling induced by glucocorticoids.
      In the first section we give a summary and update of known glucocorticoid-induced
      pathways mediating apoptosis in hematological cells. We shortly introduce
      mechanisms of glucocorticoid resistance of hematological cells. We highlight and
      discuss the emerging molecular evidence of a general induction of survival
      signaling in epithelial cells and carcinoma cells by glucocorticoids. We provide
      a model for glucocorticoid-induced resistance in cells growing in a tissue
      formation. Thus, attachment to the extracellular matrix and cell-cell contacts
      typical for e.g. epithelial and tumor cells may be crucially involved in
      switching the balance of several interacting pathways to survival upon treatment
      with glucocorticoids.

PMID- 17191113
TI  - Roles of mitogen-activated protein kinase pathways during Escherichia coli
      induced apoptosis in U937 cells.
AB  - Escherichia coli (E. coli) infections play an important and growing role in the
      clinic. In the present study, we investigated the involvement of members of the
      mitogen-activated protein kinase (MAPK) superfamily, including extracellular
      signal-regulated kinase (ERK), c-Jun NH(2)-terminal kinase (JNK) and p38 MAPK,
      and caspase-3 and 9 activity in E. coli-induced apoptosis in human U937 cells. We
      found that E. coli induces apoptosis in U937 cell lines in a dose- and time
      dependent manner, p38 MAPK and JNK were activated after 10 min of infection with
      E. coli. In contrast, ERK1/2 was down-regulated in a time-dependent manner. The
      levels of total (phosphorylation state-independent) p38 MAPK, JNK and ERK1/2 did
      not change in E. coli-infected U937 cells at all times examined. Moreover,
      exposure of U937 cells to E. coli led to caspase-3 and 9 activity. For the
      evaluation of the role of MAPKs, PD98059, SB203580 and SP600125 were used as
      MAPKs inhibitors for ERK1/2, p38 MAPK and JNK. Inhibition of ERK1/2 with PD98059
      caused further enhancement in apoptosis and caspase-3 and 9 activity, while a
      selective p38 MAPK inhibitor, SB203580 and JNK inhibitor, SP600125 significantly
      inhibited E. coli-induced apoptosis and caspase-3 and 9 activity in U937 cells.
      The results were further confirmed by the observation that the caspase inhibitors
      Z-DEVD-FMK and Z-LEHD-FMK blocked E. coli-induced U937 apoptosis. Taken together,
      we have shown that E. coli increase p38 MAPK and JNK and decrease ERK1/2
      phosphorylation and increase caspase-3 and 9 activity in U937 cells.

PMID- 17191114
TI  - The role of membrane lipids in the induction of macrophage apoptosis by
      microparticles.
AB  - Microparticles are membrane-derived vesicles that are released from cells during
      activation or cell death. These particles can serve as mediators of intercellular
      cross-talk and induce a variety of cellular responses. Previous studies have
      shown that macrophages undergo apoptosis after phagocytosing microparticles.
      Here, we have addressed the hypothesis that microparticles trigger this process
      via lipid pathways. In these experiments, microparticles induced apoptosis in
      primary macrophage cells or cell lines (RAW 264.7 or U937) with up to a 5-fold
      increase. Preincubation of macrophages with phosphatidylinositol-3,5-bisphosphate
      (PtdIns(3,5)BP) reduced the microparticle-induced apoptosis in a dose-dependent
      manner. PtdIns(3,5)BP is a specific inhibitor of the acid sphingomyelinase and
      thus can block the generation of pro-apoptotic ceramides. Similarly, the pre
      incubation of macrophages with PtdIns(3,5)BP prevented microparticle-induced
      upregulation of caspase 8, which is a major target molecule of ceramide action in
      the apoptosis pathway. PtdIns(3,5)BP, however, had no effect on the spontaneous
      rate of apoptosis. To evaluate further signaling pathways induced by
      microparticles, the extracellular signal regulated kinase (ERK-) 1 was
      investigated. This kinase plays a role in activating phospholipases A2 which
      cleaves membrane phospholipids into arachidonic acid; microparticles have been
      suggested to be a preferred substrate for phospholipases A2. As shown in our
      experiments, microparticles strongly increased the amount of phosphorylated
      ERK1/2 in RAW 264.7 macrophages in a time-dependent manner, peaking 15 min after
      co-incubation. Addition of PD98059, a specific inhibitor of ERK1, prevented the
      increase in apoptosis of RAW 264.7 macrophages. Together, these data suggest that
      microparticles perturb lipid homeostasis of macrophages and thereby induce
      apoptosis. These results emphasize the importance of biolipids in the cellular
      cross-talk of immune cells. Based on the fact that in clinical situations with
      excessive cell death such as malignancies, autoimmune diseases and following
      chemotherapies high levels of circulating microparticles might modulate
      phagocytosing cells, a suppression of the immune response might occur due to loss
      of macrophages.

PMID- 17191115
TI  - "Systemic apoptotic response" after thermal burns.
AB  - The systemic pathophysiologic changes following thermal injuries affect multiple
      organs and body systems leading to clinical manifestations including shock,
      intestinal alterations, respiratory and renal failure, immunosuppression and
      others. Recent advances in the comprehension of mechanisms underlying systemic
      complications of thermal injuries have contributed to uncover part of the
      cellular and molecular basis that underlie such changes. Recently, programmed
      cell death (apoptosis) has been considered playing an important role in the
      development of such pathological events. Therefore, investigators utilizing
      animal models and clinical studies involving human primates have produced a large
      body of information suggesting that apoptosis is associated with most of the
      tissue damages triggered by severe thermal injuries. In order to draw the
      attention on the important role of apoptosis on systemic complications of thermal
      injuries, in this review we describe most of these studies, discuss possible
      cellular and molecular mechanisms and indicate ways to utilize them for the
      development of therapeutic strategies by which apoptosis may be prevented or
      counteracted.

PMID- 17191116
TI  - Alpha-tocopheryl succinate sensitizes human colon cancer cells to exisulind
      induced apoptosis.
AB  - Sulindac sulfone (also known as exisulind) and its chemical derivatives are
      promising anticancer agents capable of inducing apoptosis in a variety of
      malignant cell types with minimal toxicity to normal cells. Here, we tested the
      ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent,
      to sensitize colon cancer cells to exisulind-induced apoptosis. We found that sub
      apoptotic doses of TOS greatly enhanced exisulind-induced growth suppression and
      apoptosis in the HCT116, LoVo and SNU-C4 human colon cancer cell lines. Our
      results revealed that this was accounted for primarily by an augmented cleavage
      of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8, -9
      and -3. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor), z-IETD-FMK (a
      caspase-8 inhibitor) or z-LEHD-FMK (a caspase-9 inhibitor) blocked TOS and
      exisulind cotreatment-induced PARP cleavage and apoptosis. Furthermore,
      TOS/exisulind cotreatment induced JNK phosphorylation, while pretreatment with
      SP600151 (a JNK inhibitor) partially blocked cotreatment-induced caspase
      dependent PARP cleavage and apoptosis. Taken together, these findings indicate
      that TOS sensitizes human colon cancer cells to exisulind-induced apoptosis.
      Apoptotic synergy induced by exisulind plus TOS seems likely to be mediated
      through a mechanism involving activation of caspases and JNK.

PMID- 17191117
TI  - Identification of poly-reactive natural IgM antibody that recognizes late
      apoptotic cells and promotes phagocytosis of the cells.
AB  - Natural IgM can recognize apoptotic cells, but the molecular structure and the
      role in macrophage phagocytosis of apoptotic cells remain unclear. OBJECTIVES:
      (1) To examine the binding of previously isolated natural IgM (3B4) to apoptotic
      cells and its effects on phagocytosis of apoptotic cells. (2) To characterize the
      molecular structure of 3B4. METHODS: 3B4 binding to apoptotic thymocytes was
      examined by flow cytometry. Polyreactivity of 3B4 was assayed by ELISA. PKH26
      labeled Macrophages were incubated with PKH67-stained apoptotic cells in the
      presence of 3B4. Macrophages phagocytosis of apoptotic cell was evaluated by flow
      cytometry. The DNA segments of 3B V(H) and V(K) were sequenced and analyzed.
      RESULTS: 3B4 IgM recognized late apoptotic cells. Polyreactive-recognitions of
      lysophosphatidylcholine (LPC) as well as some autoantigens were observed in 3B4.
      Phagocytosis of late apoptotic cells was increased in the presence of 3B4. The
      V(H) and V(K) genes of 3B4 showed a germline gene context, while N-sequences and
      nucleotide loss were observed in CDR3. CONCLUSION: 3B4 promotes macrophage
      phagocytosis of late apoptotic cells in a complement-independent process. 3B4 has
      a germline configuration and is possibly ligand-selected. Out experiments suggest
      an independent role of natural IgM as opsonin in clearance of late apoptotic
      cells.

PMID- 17191118
TI  - The role of PKCzeta in amikacin-induced apoptosis in the cochlea: prevention by
      aspirin.
AB  - Aminoglycoside antibiotics are ototoxic, inducing irreversible sensorineural
      hearing loss mediated by oxidative and excitotoxic stresses. The NF-kappaB
      pathway is involved in the response to aminoglycoside damage in the cochlea.
      However, the molecular mechanisms of this ototoxicity remain unclear. We
      investigated the expression of PKCzeta, a key regulator of NF-kappaB activation,
      in response to aminoglycoside treatment. Amikacin induced PKCzeta cleavage and
      nuclear translocation. These events were concomitant with chromatin condensation
      and paralleled the decrease in NF-kappaB (p65) levels in the nucleus. Amikacin
      also induced the nuclear translocation of apoptotic inducing factor (AIF). Prior
      treatment with aspirin prevented PKCzeta cleavage and nuclear translocation.
      Thus, aspirin counteracts the early effects of amikacin, thereby protecting hair
      cells and spiral ganglion neurons. These results demonstrate that PKCzeta acts as
      sentinel connecting specific survival pathways to mediate cellular responses to
      amikacin ototoxicity.

PMID- 17191120
TI  - Apoptosis induced by crocidolite asbestos in human lung epithelial cells involves
      inactivation of Akt and MAPK pathways.
AB  - Exposure of human lung epithelial (A549) cells to asbestos fibers causes
      apoptosis, which is largely attributed to release of iron and generation of
      reactive oxygen species (ROS) within the cells. To mimic the highly oxidative
      environment generated by asbestos exposure in the absence of the actual fibers,
      we used two chemicals; buthione sulfoximine (BSO), an inhibitor of glutathione
      (GSH) synthesis and ferric ammonium citrate (FAC), a source of iron. Here, we
      report that exposure of A549 cells to crocidolite asbestos led to a significant
      time-dependent inactivation of signaling proteins, i.e. Akt and all mitogen
      activated protein kinases (MAPKs) (p38, ERK1/2 and SAPK/JNK), and subsequently to
      apoptosis. Unlike crocidolite treatment, the use of BSO and FAC, independently or
      combined, did not change the phosphorylation status of proteins, nor did it
      induce apoptosis. Taken together, our results presented herein point to the
      possibility that crocidolite-induced apoptosis of human lung epithelial cells is
      not a mere consequence of generation of oxidants but also requires inactivation
      of major cell growth and differentiation pathways.

PMID- 17191119
TI  - Cleavage of MAGI-1, a tight junction PDZ protein, by caspases is an important
      step for cell-cell detachment in apoptosis.
AB  - MAGI-1, a member of the MAGUK family of proteins, is shown to be rapidly cleaved
      during Fas-induced apoptosis in mouse 3T3 A31 cells, and in UV irradiation- and
      staurosporine-induced apoptosis in HaCaT cells. This generates a 97 kDa N
      terminal fragment that dissociates from the cell membrane; a process that is
      largely prevented in the presence of the caspase inhibitor Z-VAD-fmk. In
      addition, we show that in vitro translated radiolabelled MAGI-1 is efficiently
      cleaved into 97 kDa and 68 kDa fragments by caspases-3 and -7 at physiological
      concentrations and mutating the MAGI-1 Asp(761) to Ala completely abolished the
      caspase-induced cleavage. Moreover, in HaCaT cells overexpressing the MAGI-1
      Asp(761)Ala mutant the disruption of cell-cell contacts was delayed during
      apoptosis, whereas other caspase-dependent processes such as nuclear condensation
      were not affected, suggesting that cell detachment is parallel to them. Thus,
      MAGI-1 cleavage appears to be an important step in the disassembly of cell-cell
      contacts during apoptosis.

PMID- 17191122
TI  - The anti-Fas antibody M-20 cross-reacts with intracellular proteins: implications
      for false-positive detection of Fas.

PMID- 17191121
TI  - NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced
      apoptosis in HCT116 colon carcinoma cells.
AB  - Quercetin, a flavonoid molecule ubiquitously present in nature, has multiple
      effects on cancer cells, including the inhibition of cell proliferation and
      migration. However, the responsible molecular mechanisms are not fully
      understood. We found that quercetin induces the expression of NAG-1 (Non
      steroidal anti-inflammatory drug activated gene-1), a TGF-beta superfamily
      protein, during quercetin-induced apoptosis of HCT116 human colon carcinoma
      cells. Reporter assays using the luciferase constructs containing NAG-1 promoter
      region demonstrate that early growth response-1 (EGR-1) and p53 are required for
      quercetin-mediated activation of the NAG-1 promoter. Overexpression of NAG-1
      enhanced the apoptotic effect of quercetin, but suppression of quercetin-induced
      NAG-1 expression by NAG-1 siRNA attenuated quercetin-induced apoptosis in HCT116
      cells. Taken together, the present study demonstrates for the first time that
      quercetin induces apoptosis via NAG-1, providing a mechanistic basis for the
      apoptotic effect of quercetin in colon carcinoma cells.

PMID- 17191123
TI  - Reticulon 3 mediates Bcl-2 accumulation in mitochondria in response to
      endoplasmic reticulum stress.
AB  - Reticulon3 (RTN3), firstly isolated from the retina and widely expressed in human
      tissues with the highest expression in the brain, is presumed to play an
      important role in the developing axons through the transport of liquids and
      proteins. We have identified and characterized RTN3 as a RTN4B/ASY interaction
      protein. Here we demonstrated that ER-stress activated RTN3 expression. CHOP and
      ATF6 were sufficient to up-regulate the expression of RTN3. The down-regulation
      of RTN3 would induce apoptosis and attenuate the anti-apoptotic activity of Bcl
      2, indicating RTN3 was required for the cellular survival and optimal anti
      apoptotic activity of Bcl-2. Our present studies also indicated ER-stress induced
      RTN3 up-regulation could trigger Bcl-2 translocation from ER to mitochondria.
      Moreover, the previous studies showed that RTN4B was also a Bcl-2-interacted
      protein. We found that RTN3 and RTN4B could block the access of Bcl-2 to each
      other and thereafter determined the Bcl-2 subcellular distribution. Taken
      together, our findings indicate that RTN3 is directly involved in the ER
      constituents trafficking events through dually acting as an essential and
      important ER-stress sensor, and a trigger for the Bcl-2 translocation.

PMID- 17191125
TI  - Comparison of three methods to assess enteric neuronal apoptosis in patients with
      slow transit constipation.
AB  - BACKGROUND: The pathophysiological basis of slow transit constipation are
      scarcely understood. Some recent evidence suggests that increased apoptotic
      phenomena in the colonic enteric neurons may play a role. However, the best
      method to assess these phenomena has not been evaluated. AIMS: To compare three
      different methods to detect enteric neuronal apoptosis in these patients.
      METHODS: Serial colonic tissue sections obtained in 10 patients with intractable
      slow transit constipation were evaluated with immunohistochemical methods aimed
      at evaluating apoptotic phenomena: the formamide-MAb method, the TUNEL, and the
      caspase-3. RESULTS: The highest yield of apoptotic neurons was obtained by means
      of the formamide-MAb method, compared to the other two, whereas the lowest yield
      was observed with the caspase-3. CONCLUSIONS: The formamide-MAb method, which is
      able to distinguish apoptosis from necrosis and is not influenced by DNA breaks,
      may prove useful to assess neuronal apoptotic phenomena in the human enteric
      nervous system. This represents a relevant method to detect enteric neuronal
      apoptosis.

PMID- 17191124
TI  - The marine sphingolipid-derived compound ES 285 triggers an atypical cell death
      pathway.
AB  - The isolation of new molecules from marine sources opens the door to their
      possible therapeutic use against tumors and other pathological conditions.
      Indeed, we recently defined the cytotoxicity of ES 285, obtained from the clam
      Mactromeris polynima, and its affects on the cells microfilament but not the
      microtubule network. Considering the analogy between ES 285 and sphingosine
      related lipids, we wondered whether ES 285 might affect the activity of PKC at
      the intracellular level. While we anticipated that ES 285 might inhibit PKC, it
      turns out that in contrast it serves to activate PKC at the cellular level.
      Indeed, like other sphingosine-related lipids, ES 285 induces the phosphorylation
      of MARCKS. Additionally, we further examined the cytotoxicity of ES 285 to
      elucidate the molecular mechanisms through which this compound triggers
      apoptosis. When the influence of ES 285 on "cell death markers" was assessed, it
      became clear that ES285 activates caspase 3 and 12, and that it modified the
      phosphorylation of p53. In contrast, ES 285 does not affect other pathways widely
      implicated in regulating cell survival/apoptosis, such as JNK, Erks or Akt. Thus,
      these data suggest that ES 285-triggers an atypical cell death program when
      compared to other sphingosine-dependent apoptosis pathways.

PMID- 17191126
TI  - Different levels of p53 induced either apoptosis or cell cycle arrest in a
      doxycycline-regulated hepatocellular carcinoma cell line in vitro.
AB  - Induction of p53 gene expression in cancer cells can lead to both cell cycle
      arrest and apoptosis. To clarify whether the level of p53 expression determines
      the apoptotic response of hepatocellular carcinoma (HCC) cells, we assessed the
      effect of various levels of expression of p53 gene on a p53-deficient HCC cell
      line, Hep3B, utilizing a doxycycline (Dox)-regulated inducible p53 expression
      system. Our results showed that apoptosis was induced in HCC cells with high
      levels of p53 expression. However, lower level of p53 expression induced only
      cell cycle arrest but not apoptosis. Bax expression was up-regulated following
      high levels of p53 expression, while bcl-2 expression was not altered by the
      level of p53 expression. Moreover, p21 expression was observed in both high and
      low expression of p53. These results suggest the level of p53 expression could
      determine if the HCC cells would go into cell cycle arrest or apoptosis. Bax may
      participate, at least in part, in inducing p53-dependent apoptosis and the
      induction of p21 alone was able to cause cell cycle arrest but not apoptosis.

PMID- 17191127
TI  - Adhesion and function of human endothelial cells co-cultured on smooth muscle
      cells.
AB  - To evaluate interactions between human endothelial cells (ECs) and smooth muscle
      cells (SMCs) for the development of tissue-engineered vessels, we examined the
      adhesion and key cell properties of human ECs grown on quiescent human aortic
      SMCs. ECs attached to SMCs spread more slowly than ECs attached to fibronectin
      surfaces, and ECs aligned along the direction of the SMCs. ECs attached firmly
      and less than 5% of the cells were removed by shear stresses as high as 300 dyn
      cm(-2). Unlike porcine SMCs and co-cultures, human SMCs or co-cultures do not
      contract under flow, and the human ECs and SMCs in co-culture align toward the
      direction of flow. A confluent endothelium could be maintained in co-culture for
      over 30 days, and some of the ECs reoriented perpendicular to the SMCs after 9
      days in static culture. Surface tissue factor levels in ECs and SMCs were less in
      co-culture than in monoculture. Co-culture induced an increase in calponin
      expression in SMCs. These findings show that human co-cultures can be maintained
      for long culture periods, where the endothelium remains confluent and responds to
      long-term exposure to flow, and EC-SMC interactions lead to an increase in SMC
      differentiation and an EC surface that is less thrombotic.

PMID- 17191128
TI  - Temperature dependent soret spectral band shifts accompany human CN
      mesohemoglobin assembly.
AB  - The interaction between human apohemoglobin A and CN-Mesohemin, a monomeric non
      native heme derivative, was probed by Soret spectrophotometric titrations in 0.05
      M potassium phosphate buffer, pH 7 at varied temperatures. Hypsochromic shifts in
      the absorbance maxima were observed at all temperatures below 10 degrees C. First
      derivative spectroscopy of CN-Mesohemin titrations was used to provide further
      evidence of a spectral shift upon CN-Mesohemoglobin assembly. Findings of Soret
      Spectral shifts demonstrate a preference for the alpha chain heme site by CN
      Mesohemin indicative of semi-alpha-hemoglobin intermediate formation. CN
      Mesohemin, a derivative with peripheral 2,4 ethyl groups, does not possess the
      extended conjugation seen for native CN-Protohemin with its 2,4 vinyl groups.
      Indeed, reduced polarity of CN-Mesohemin over that of CN-Protohemin resulted in
      distinct temperature dependencies. Molecular visualization and protein-ligand
      interaction analysis targeted a functionally diverse residue unique to the alpha
      chain. Tyrosine-42 (a polar/non-polar amino acid) appeared to play a prominent
      role in the assembly process.

PMID- 17191129
TI  - Direct mass-spectrometric identification of Arg296 and Arg299 as the methylation
      sites of hnRNP K protein for methyltransferase PRMT1.
AB  - Protein methylation is one of the most important post-translational modifications
      that contribute to the diversity and complexity of proteome. Here we report the
      study of in vitro methylation of heterogeneous nuclear ribonucleoprotein K (hnRNP
      K) with protein arginine methyltransferase 1 (PRMT1), as an enzyme, and S
      adenosyl-L-methionine (SAM), as a methyl donor. The mass analysis of tryptic
      peptides of hnRNP K before and after methylation reveals the addition of four
      methyl groups in the residues 288-303. Tandem mass-spectrometric analysis of this
      peptide shows that both Arg296 and Arg299 are dimethylated. In addition,
      fragmentation analysis of such methylated arginines illustrate that they are both
      asymmetric dimethylarginines. Since Arg296 and Arg299 are located near the SH3
      binding domains of hnRNP K, such methylation has the potential in regulating the
      interaction of hnRNP K with Src protein family. Our results provide crucial
      information for further functional study of hnRNP K methylation.

PMID- 17191130
TI  - Genetic program of neuronal differentiation and growth induced by specific
      activation of NMDA receptors.
AB  - Glutamate and its receptors are expressed very early during development and may
      play important roles in neurogenesis, synapse formation and brain wiring. The
      levels of glutamate and activity of its receptors can be influenced by exogenous
      factors, leading to neurodevelopmental disorders. To investigate the role of NMDA
      receptors on gene regulation in a neuronal model, we used primary neuronal
      cultures developed from embryonic rat cerebri in serum-free medium. Using
      Affymetrix Gene Arrays, we found that genes known to be involved in neuronal
      plasticity were differentially expressed 24 h after a brief activation of NMDA
      receptors. The upregulation of these genes was accompanied by a sustained
      induction of CREB phosphorylation, and an increase in synaptophysin
      immunoreactivity. We conclude that NMDA receptor activation elicits expression of
      genes whose downstream products are involved in the regulation of early phases of
      the process leading to synaptogenesis and its consolidation, at least in part
      through sustained CREB phosphorylation.

PMID- 17191131
TI  - Human mesenchymal stem cells signals regulate neural stem cell fate.
AB  - Neural stem cells (NSCs) differentiate into neurons, astrocytes and
      oligodendrocytes depending on their location within the central nervous system
      (CNS). The cellular and molecular cues mediating end-stage cell fate choices are
      not completely understood. The retention of multipotent NSCs in the adult CNS
      raises the possibility that selective recruitment of their progeny to specific
      lineages may facilitate repair in a spectrum of neuropathological conditions.
      Previous studies suggest that adult human bone marrow derived mesenchymal stem
      cells (hMSCs) improve functional outcome after a wide range of CNS insults,
      probably through their trophic influence. In the context of such trophic
      activity, here we demonstrate that hMSCs in culture provide humoral signals that
      selectively promote the genesis of neurons and oligodendrocytes from NSCs. Cell
      cell contacts were less effective and the proportion of hMSCs that could be
      induced to express neural characteristics was very small. We propose that the
      selective promotion of neuronal and oligodendroglial fates in neural stem cell
      progeny is responsible for the ability of MSCs to enhance recovery after a wide
      range of CNS injuries.

PMID- 17191132
TI  - Randomized clinical stroke rehabilitation trials in 2005.
AB  - This article reviews randomized control trials (RCTs) undertaken in stroke
      rehabilitation in the year 2005. A Medline search generated 31 RCTs in stroke
      rehabilitation in the year 2005 in the English language. These trials were
      primarily efficacy studies of a number of treatments: medications such as folate,
      vitamin B12 and bisphosphonates in preventing osteoporotic related hip fractures,
      compression stockings in preventing deep vein thrombosis (DVT), use of mechanical
      robots and positioning of the upper limb to help improve function; and,
      transcranial magnetic coil stimulation, acupuncture and neural tissue transplant
      to enhance motor recovery in post-stroke patients.

PMID- 17191133
TI  - Relation of plasma homocysteine to plasma amyloid beta levels.
AB  - BACKGROUND: Elevated plasma homocysteine and amyloid beta (Abeta) have been
      associated with Alzheimer's disease (AD). We investigated the cross-sectional
      association between these biomarkers. METHODS: We used linear regression to
      relate plasma homocysteine and Abeta adjusting for age, gender, creatinine, APOE
      epsilon4, and ethnic group in 327 persons aged 78 +/- 6.6 years. RESULTS: Plasma
      homocysteine correlated with age, serum creatinine, plasma Abeta40 and Abeta42,
      and was inversely correlated with serum vitamin B12, and folate. Abeta42, but not
      Abeta40, was related to later development of dementia. Homocysteine was related
      to higher Abeta40 levels (coefficient = 2.0; P < 0.0001) and this association was
      attenuated after adjustment for creatinine (coefficient = 1.0; P < 0.0001). The
      crude association between homocysteine and Abeta42 was weaker (coefficient = 0.5;
      P = 0.01) and became non-significant after adjustment for creatinine (coefficient
      = 0.4; P = 0.06). These associations were unrelated to ethnicity, the presence of
      APOE-epsilon4 or dementia. Analyses by quartiles of homocysteine showed that
      these association were driven primarily by the fourth quartile. CONCLUSIONS:
      Plasma homocysteine is directly related to Abeta40. The association with Abeta42
      is not significant. These results seem to indicate that homocysteine is related
      to aging but not specifically to AD.

PMID- 17191134
TI  - Anoxia-induced changes in pyridine nucleotide redox state in cortical neurons and
      astrocytes.
AB  - NAD(P)H autofluorescence was used to verify establishment of metabolic anoxia
      using primary cultures of cortical neurons and astrocytes. Cells on cover slips
      were placed in a chamber and O(2) was displaced by continuous infusion of argon.
      Perfusion with medium at PO(2) < 0.4 mm Hg caused an increase in NAD(P)H
      fluorescence, albeit to levels lower than that obtained with cyanide. Addition of
      the nitric oxide-generating agent DETA-NO to the hypoxic medium further increased
      fluorescence to the level with cyanide. Fluorescence under anoxia remained high
      in the presence of glucose, but declined in neurons and not in astrocytes when
      glucose was substituted with 2-deoxyglucose. Reoxygenation of neurons resulted in
      a decline in fluorescence and a loss in fluorescent gradient between fully
      reduced and fully oxidized (plus respiratory uncoupler). We conclude that (1)
      DETA-NO is useful for generating metabolic anoxia in the presence of argon (2)
      Exogenous glucose is necessary to maintain NAD(P)H in a reduced state during
      metabolic anoxia in neurons but not astrocytes (3) Neurons undergo a partially
      irreversible decline in NAD(P)H fluorescence during metabolic anoxia and
      reoxygenation that could contribute to prolonged metabolic failure.

PMID- 17191136
TI  - Expression of a myelin proteolipid protein (Plp)-lacZ transgene is reduced in
      both the CNS and PNS of Plp(jp) mice.
AB  - Jimpy (Plp(jp)) is an X-linked recessive mutation in mice that causes CNS
      dysmyelination and early death in affected males. It results from a point
      mutation in the acceptor splice site of myelin proteolipid protein (Plp) exon 5,
      producing transcripts that are missing exon 5, with a concomitant shift in the
      downstream reading frame. Expression of the mutant PLP product in Plp(jp) males
      leads to hypomyelination and oligodendrocyte death. Expression of our Plp-lacZ
      fusion gene, PLP(+)Z, in transgenic mice is an excellent readout for endogenous
      Plp transcriptional activity. The current studies assess expression of the
      PLP(+)Z transgene in the Plp(jp) background. These studies demonstrate that
      expression of the transgene is decreased in both the central and peripheral
      nervous systems of affected Plp(jp) males. Thus, expression of mutated PLP
      protein downregulates Plp gene activity both in oligodendrocytes, which
      eventually die, and in Schwann cells, which are apparently unaffected in Plp(jp)
      mice.

PMID- 17191137
TI  - Tetrahydrobiopterin availability in Parkinson's and Alzheimer's disease;
      potential pathogenic mechanisms.
AB  - Within the central nervous system, tetrahydrobiopterin (BH4) is an essential
      cofactor for dopamine and serotonin synthesis. In addition, BH4 is now
      established to be an essential cofactor for all isoforms of nitric oxide synthase
      (NOS). Inborn errors of metabolism affecting BH4 availability are well documented
      and the clinical presentation can be attributed to a paucity of dopamine,
      serotonin, and nitric oxide (NO) generation. In this article, we have focussed
      upon the sensitivity of BH4 to oxidative catabolism and the observation that when
      BH4 is limiting some cellular sources of NOS may generate superoxide whilst other
      BH4 saturated NOS enzymes may be generating NO. Such a scenario could favor
      peroxynitrite generation. If peroxynitrite is not scavenged, e.g., by
      antioxidants such as reduced glutathione, irreversible damage to critical
      cellular enzymes could ensue. Such targets include components of the
      mitochondrial electron transport chain, alpha ketoglutarate dehydrogenase and
      possibly pyruvate dehydrogenase. Such a cascade of events is hypothesized, in
      this article, to occur in neurodegenerative conditions such as Parkinson's and
      Alzheimer's disease.

PMID- 17191135
TI  - Redox regulation of cellular stress response in aging and neurodegenerative
      disorders: role of vitagenes.
AB  - Reduced expression and/or activity of antioxidant proteins lead to oxidative
      stress, accelerated aging and neurodegeneration. However, while excess reactive
      oxygen species (ROS) are toxic, regulated ROS play an important role in cell
      signaling. Perturbation of redox status, mutations favoring protein misfolding,
      altered glyc(osyl)ation, overloading of the product of polyunsaturated fatty acid
      peroxidation (hydroxynonenals, HNE) or cholesterol oxidation, can disrupt redox
      homeostasis. Collectively or individually these effects may impose stress and
      lead to accumulation of unfolded or misfolded proteins in brain cells.
      Alzheimer's (AD), Parkinson's and Huntington's disease, amyotrophic lateral
      sclerosis and Friedreich's ataxia are major neurological disorders associated
      with production of abnormally aggregated proteins and, as such, belong to the so
      called "protein conformational diseases". The pathogenic aggregation of proteins
      in non-native conformation is generally associated with metabolic derangements
      and excessive production of ROS. The "unfolded protein response" has evolved to
      prevent accumulation of unfolded or misfolded proteins. Recent discoveries of the
      mechanisms of cellular stress signaling have led to new insights into the diverse
      processes that are regulated by cellular stress responses. The brain detects and
      overcomes oxidative stress by a complex network of "longevity assurance
      processes" integrated to the expression of genes termed vitagenes. Heat-shock
      proteins are highly conserved and facilitate correct protein folding. Heme
      oxygenase-1, an inducible and redox-regulated enzyme, has having an important
      role in cellular antioxidant defense. An emerging concept is neuroprotection
      afforded by heme oxygenase by its heme degrading activity and tissue-specific
      antioxidant effects, due to its products carbon monoxide and biliverdin, which is
      then reduced by biliverdin reductase in bilirubin. There is increasing interest
      in dietary compounds that can inhibit, retard or reverse the steps leading to
      neurodegeneration in AD. Specifically any dietary components that inhibit
      inappropriate inflammation, AbetaP oligomerization and consequent increased
      apoptosis are of particular interest, with respect to a chronic inflammatory
      response, brain injury and beta-amyloid associated pathology. Curcumin and
      ferulic acid, the first from the curry spice turmeric and the second a major
      constituent of fruit and vegetables, are candidates in this regard. Not only do
      these compounds serve as antioxidants but, in addition, they are strong inducers
      of the heat-shock response. Food supplementation with curcumin and ferulic acid
      are therefore being considered as a novel nutritional approach to reduce
      oxidative damage and amyloid pathology in AD. We review here some of the emerging
      concepts of pathways to neurodegeneration and how these may be overcome by a
      nutritional approach.

PMID- 17191139
TI  - Differential changes in phosphorylation of tau at PHF-1 and 12E8 epitopes during
      brain ischemia and reperfusion in gerbils.
AB  - Cortical neurons are vulnerable to ischemic insult, which may cause cytoskeletal
      changes and neurodegeneration. Tau is a microtubule-associated protein expressed
      in neuronal and glial cells. We examined the phosphorylation status of tau
      protein in the gerbil brain cortex during 5 min ischemia induced by bilateral
      common carotid artery occlusion followed by reperfusion for 20 min to 7 days.
      Control brain homogenates contained 63, 65 and 68 kD polypeptides of tau
      immunoreactive with Alz 50, Tau 14 and Tau 46 antibodies raised against non
      phosphorylated tau epitopes. Gerbil tau was also immunoreactive with some (PHF-1
      and 12E8) but not all (AT8, AT100, AT180 and AT270) antibodies raised against
      phosphorylated tau epitopes. PHF-1 recognized a single 68 kD polypeptide and 12E8
      bound the 63 kD polypeptide. During 5 min ischemia, PHF-1 immunoreactivity
      declined to 6%, then recovered to control levels after 20 min of blood
      recirculation and subsequently increased above control values 3 and 7 days later.
      In contrast, 12E8 immunoreactivity remained stable during ischemia and
      reperfusion. Our results suggest that the two phosphorylated epitopes of tau are
      regulated by different mechanisms and may play different roles in microtubule
      dynamics. They may also define various pools of neuronal/glial cells vulnerable
      to ischemia.

PMID- 17191141
TI  - Readiness for HIV testing among young people in northern Nigeria: the roles of
      social norm and perceived stigma.
AB  - This study examined the predictors of readiness for HIV testing among young
      people in northern Nigeria, paying special attention to the role of stigma.
      Stigma is measured at two levels: individual and community (social norm). There
      are commonalities and differences in the correlates of readiness among men and
      women. For men and women, knowledge about HIV prevention, knowledge about a
      source for VCT, discussion about condom use for HIV prevention and perceived risk
      are strong predictors. Knowledge that an apparently healthy person can be HIV
      infected is only significant for women. Perceived stigma is a significant
      predictor for both men and women although the specific dimension of note differs
      between the sexes. Social norm is strongly and directly associated with readiness
      among men but has no apparent influence among women. For both sexes, social norm
      appears to have strong mediating influence on the relationship between personal
      perceived stigma and readiness. The results strongly suggest that to eliminate
      HIV-related stigma, it is not enough to target individual cognitive processes;
      strategic efforts should target social structures in order to change negative
      social norms.

PMID- 17191138
TI  - Alzheimer's disease and cholesterol: the fat connection.
AB  - Since the discovery of the significance of the cholesterol-carrying
      apolipoprotein E and cholesterolaemia as major risk factors for Alzheimer's
      Disease (AD) there has been a mounting interest in the role of this lipid as a
      possible pathogenic agent. In this review we analyse the current evidence linking
      cholesterol metabolism and regulation in the CNS with the known mechanisms
      underlying the development of Alzheimer's Disease. Cholesterol is known to affect
      amyloid-beta generation and toxicity, although it must be considered that the
      results studies using the statin class of drugs to lower plasma cholesterol may
      be affected by other effects associated with these drugs. Finally, we report some
      of our results pointing at the interplay between neurons and astrocytes and NADPH
      oxidase activation as a new candidate mechanism linking cholesterol and AD
      pathology.

PMID- 17191142
TI  - Should embryo donation be actively encouraged and advocated for couples with only
      one infertile partner?

PMID- 17191140
TI  - Cyclic GMP-dependent pathways protect differentiated oligodendrocytes from
      multiple types of injury.
AB  - The cyclic GMP analog 8-bromo-cyclic GMP (8-Br-cGMP) protects differentiated
      murine oligodendrocytes (OLs) from caspase-mediated death initiated by
      staurosporine, thapsigargin or kainate. Caspase-independent death caused by high
      levels of NO is also partially prevented by 8-Br-cGMP. Inhibitors of protein
      kinase G (cGMP-dependent protein kinase, cGK) reversed protection, supporting
      involvement of cGK. Since NO stimulates soluble guanylate cyclase, increasing
      cGMP, we treated OLs with low levels of NO and observed partial protection
      against thapsigargin, staurosporine and kainate. Two inhibitors of mitochondrial
      pore transition (MPT), cyclosporin A and bongkrekic acid, were poorly protective,
      indicating that cGMP is not acting primarily by blocking MPT. 8Br-cGMP was more
      effective than 8Br-cAMP in protecting against staurosporine or release of
      intracellular Ca(++) by thapsigargin. The cAMP analog exhibited little or no
      protection against kainate or high levels of NO. Thus cGK signaling is more
      effective than protein kinase A or phosphodiesterase 3 signaling in preventing OL
      death.

PMID- 17191143
TI  - Does providing extended relapse prevention bibliotherapy to problem gamblers
      improve outcome?
AB  - Relapse rates among pathological gamblers are high with as many as 75% of
      gamblers returning to gambling shortly after a serious attempt to quit. The
      present study focused on providing a low cost, easy to access relapse prevention
      program to such individuals. Based on information collected in our ongoing study
      of the process of relapse, a series of relapse prevention booklets were developed
      and evaluated. Individuals who had recently quit gambling (N = 169) were
      recruited (through media announcements) and randomly assigned to a single mailing
      condition in which they received one booklet summarizing all of the relapse
      prevention information or a repeated mailing condition in which they received the
      summary booklet plus 7 additional booklets mailed to them at regular intervals
      over the course of a year period. Gambling involvement over the course of the 12
      month follow-up period, confirmed by family or friends, was compared between the
      two groups. Results indicated that participants receiving the repeated mailings
      were more likely to meet their goal, but they did not differ from participants
      receiving the single mailing in frequency of gambling or extent of gambling
      losses. The results of this project suggest that providing extended relapse
      prevention bibliotherapy to problem gamblers does not improve outcome. However,
      providing the overview booklet may be a low cost, easy to access alternative for
      individuals who have quit gambling.

PMID- 17191144
TI  - A cross-cultural study of gambling behaviour among adolescents.
AB  - This study investigated whether the prevalence of weekly and problem gambling
      among youth varied according to cultural affiliation. A convenience sample of
      1,265 Quebec high school students aged 12-18 was divided into three linguistic
      groupings: Anglophone (English), Francophone (French), and Allophone (other).
      Results revealed that the Allophone grouping contained the highest proportion of
      youth who gambled on a weekly basis and who reported gambling problems, followed
      by the Anglophone, and finally the Francophone groupings. Acculturation
      difficulties were associated with problem gambling. Few meaningful between-group
      differences were found with respect to factors related to problem gambling (i.e.,
      comorbidity with other risk factors, coping, family functioning and resiliency).
      The results are discussed with respect to the influence of cultural background on
      gambling behavior.

PMID- 17191146
TI  - An experiment on the social facilitation of gambling behavior.
AB  - Research and theory regarding the social facilitation effect generates the
      expectation that the presence of other gamblers (or co-actors) in a gaming venue
      is likely to intensify individual gambling behavior and magnify losses. Fifty
      male and 66 female participants (116 total) played a computer-simulated
      electronic gaming machine with a fixed winning sequence, followed by an
      indefinite losing sequence. Measures of the intensity of gambling behavior
      included the final payout (a direct measure of losses), average bet-size, number
      of trials played, and the speed of play. Some participants received false
      feedback from the computer designed to suggest that other gamers in adjacent
      rooms were playing and sometimes winning at the same game. Persons who received
      both sight and sound information, including winning bells and instant messages
      regarding the wins of other (fake) players, placed more bets and lost more money
      compared to the other conditions with less information.

PMID- 17191145
TI  - Gambling behavior of student-athletes and a student cohort: what are the odds?
AB  - This study investigated the prevalence of gambling, gambling related NCAA
      violations, and disordered gambling in student-athletes (n = 736) with a
      comparison cohort of students (n = 1,071) at four universities. Student-athletes
      reported similar rates of gambling frequency, use of a bookmaker, and disordered
      gambling as students. After accounting for demographic differences, student
      athletes were less likely to engage in sports wagering than students. Several
      risk factors for disordered gambling were identified, including being male and
      reporting at least one parent with a history of gambling problems. These findings
      suggest that problems associated with gambling are a university-wide issue with
      student-athletes meriting additional attention because of implications for the
      integrity of intercollegiate sports. Improved prevention and intervention efforts
      for collegiate gambling are recommended.

PMID- 17191147
TI  - Assessing diet quality in a population of low-income pregnant women: a comparison
      between Native Americans and whites.
AB  - OBJECTIVE: To assess diet quality of pregnant women in the WIC program in North
      Dakota and to compare Native Americans with whites, we used a DQI-P (diet quality
      index for pregnancy) among low-income pregnant women enrolled in WIC, a special
      supplemental program for women, infants, and children. METHODS: Dietary
      information was collected for all participants using the Harvard Service Food
      Frequency Questionnaire (HSFFQ). DQI-P scores were based on 10 components
      previously used in other diet quality indices: percent recommended intake of
      grains, vegetables, fruits, folate, calcium, and iron; total fat, saturated fat,
      and cholesterol; and dietary diversity. Each component contributed 10 points to
      the total possible DQI-P score of 100. RESULTS: The mean DQI-P score was 53.9.
      Native Americans (51.8) had significantly lower DQI-P scores (51.8 vs. 54.2;
      p<0.0001); significantly higher scores for iron and folate; and significantly
      lower scores for cholesterol, total fat intake, and saturated fat components than
      did whites. As DQI-P scores increased, diet improved and scores for individual
      components increased. CONCLUSION: While there were significant differences
      between the diet quality of Native American and white pregnant women, the
      differences were minimal. The DQI-P scores for all women in this population
      indicate that their diets are not meeting dietary recommendations. Interventions
      should focus on decreasing fat intake and increasing iron and folate intake to
      meet national dietary recommendations. More emphasis should be placed on eating
      whole fruit and vegetables.

PMID- 17191148
TI  - Social cognition and externalizing psychopathology: an investigation of the
      mediating role of language.
AB  - The present study integrates findings from three lines of research on the
      association of social cognition and externalizing psychopathology, language and
      externalizing psychopathology, and social cognition and language functioning
      using Structural Equation Modeling (SEM). To date these associations have been
      examined in pairs. A sample of 354 clinic-referred children (aged 7 to 14 years)
      recruited from a children's mental health centre were tested on measures of
      language, social cognition, working memory, and child psychopathology. We
      compared a hypothesized model presenting language functioning as a mediator of
      the association between social cognition and externalizing psychopathology to a
      model presenting the independent contribution of language and social cognition to
      externalizing psychopathology. As hypothesized, we found that the mediation model
      fits the data better than the alternative model. Our findings have implications
      for developing and modifying intervention techniques for children with dual
      language and externalizing psychopathology.

PMID- 17191149
TI  - The effect of natural killer cell killer Ig-like receptor alloreactivity on the
      outcome of bone marrow stem cell transplantation for severe combined
      immunodeficiency (SCID).
AB  - Natural killer (NK) cell alloreactions against recipient cells in the setting of
      bone marrow transplantation have been associated with decreased rates of graft
      versus-host disease (GVHD) and improved survival in transplant recipients with
      myeloid leukemia. These alloreactions are predicted by the absence of recipient
      HLA class I ligands for donor inhibitory killer Ig-like receptors (KIR). We
      hypothesized that donor NK cell alloreactions against recipient cells may affect
      the development of T and B-cell functions and incidence of GVHD in infants with
      severe combined immunodeficiency (SCID). Of the 156 patients with SCID who had
      received related bone marrow transplants without pretransplant chemotherapy or
      posttransplant GVHD prophylaxis, 137 patient-donor pairs were evaluated for the
      absence of recipient HLA class I ligands for donor inhibitory KIR. Analysis
      showed that the absence of a KIR ligand had no effect on the incidence or
      severity of GVHD (RR [corrected] = 0.95, p = 0.84), development of T-cell
      function (RR [corrected] = 1.05, p = 0.69), production of IgA (p = 0.46) or IgM
      (p = 0.33), or on 5-year survival (RR [corrected] = 1.21, p = 0.10). Further, in
      patients possessing native NK cells, the absence of KIR ligands in donors for
      recipient-inhibitory KIR did not alter transplantation outcomes. This study
      suggests that inhibitory KIR/HLA interactions do not play a significant role in
      bone marrow transplantation for SCID.

PMID- 17191150
TI  - Primary immunodeficiency diseases in Latin America: the second report of the
      LAGID registry.
AB  - This is the second report on the continuing efforts of LAGID to increase the
      recognition and registration of patients with primary immunodeficiency diseases
      in 12 Latin American countries: Argentina, Brazil, Chile, Colombia, Costa Rica,
      Honduras, Mexico, Panama, Paraguay, Peru, Uruguay, and Venezuela. This report
      reveals that from a total of 3321 patients registered, the most common form of
      primary immunodeficiency disease was predominantly antibody deficiency (53.2%)
      with IgA deficiency reported as the most frequent phenotype. This category was
      followed by 22.6% other well-defined ID syndromes, 9.5% combined T- and B-cell
      inmunodeficiency, 8.6% phagocytic disorders, 3.3% diseases of immune
      dysregulation, and 2.8% complement deficiencies. All countries that participated
      in the first publication in 1998 reported an increase in registered primary
      immunodeficiency cases, ranging between 10 and 80%. A comparison of the estimated
      minimal incidence of X-linked agammaglobulinemia, chronic granulomatous disease,
      and severe combined immunodeficiency between the first report and the present one
      shows an increase in the reporting of these diseases in all countries. In this
      report, the estimated minimal incidence of chronic granulomatous disease was
      between 0.72 and 1.26 cases per 100,000 births in Argentina, Chile, Costa Rica,
      and Uruguay and the incidence of severe combined immunodeficiency was 1.28 and
      3.79 per 100,000 births in Chile and Costa Rica, respectively. However, these
      diseases are underreported in other participating countries. In addition to a
      better diagnosis of primary immunodeficiency diseases, more work on improving the
      registration of patients by each participating country and by countries that have
      not yet joined LAGID is still needed.

PMID- 17191156
TI  - Evaluation of pheromones and a new trap for monitoring Agriotes lineatus and
      Agriotes obscurus in the Fraser Valley of British Columbia.
AB  - A prototype ground-based pheromone trap design, baited with various pheromone
      lures, was field tested for effectiveness in trapping male Agriotes obscurus and
      Agriotes lineatus click beetles in British Columbia. Pheromone dispensers
      containing geranyl octanoate and geranyl hexanoate in a 1:1 ratio caught the
      greatest numbers of A. obscurus, whereas those containing geranyl octanoate and
      geranyl butanoate in a 9 or 10:1 ratio caught high numbers of A. lineatus. Some
      differences in A. obscurus attraction to traps were observed between dispensers
      according to the manufacturer and the number of dispensers deployed in traps. The
      trap design and optimal pheromone dispensers tested would be suitable for
      monitoring or surveying A. obscurus and A. lineatus populations in North America.

PMID- 17191155
TI  - Chemical identification of MHC-influenced volatile compounds in mouse urine. I:
      Quantitative Proportions of Major Chemosignals.
AB  - The genes of the major histocompatibility complex (MHC) are highly polymorphic
      loci that encode cell surface proteins, class I and II molecules. They present
      peptide antigens to T cells and thereby control immunological self/nonself
      recognition. Increasing evidence indicates that MHC genes also influence odor and
      mating preferences; however, it is unclear how. Here we report the results of
      chemical analyses of male mouse urinary odors collected from a variety of mouse
      strains, including MHC-congenics, recombinants, mutants, and transgenics (i.e.,
      beta2 microglobulin "knockouts," which lack class I expression, and transporters
      associated with antigen processing (TAP) knock-outs). After the identification of
      volatile odor components by gas chromatography/mass spectrometry, the odor
      profiles of urine samples were analyzed quantitatively by using stir bar sorptive
      extraction and gas chromatography/atomic emission detection. Results showed that
      MHC genes influenced the amounts of testosterone-mediated pheromones, sulfur
      containing compounds, and several carbonyl metabolites. This is the first report
      to quantitatively link known mouse pheromones to classical, antigen-binding MHC
      loci. Surprisingly, these compounds were not influenced by TAP genes, even though
      these loci are MHC-linked and play a role in peptide presentation. Whereas
      identification of MHC-determined odorants does not reveal their metabolic origin,
      some constituents were also present in blood serum, and their levels were not
      altered by antibiotics.

PMID- 17191157
TI  - Jasmonate, salicylate, and benzoate in insect eggs.
AB  - Jasmonic acid (JA) and salicylic acid (SA) are key molecules in the initiation of
      plant defensive responses to attack by herbivores and pathogens, respectively.
      Our previous work has shown that JA occurs at high concentrations in eggs and
      neonates of lepidopteran species. Here, we extend our analyses to eggs of 15 non
      lepidopteran insect species spanning eight orders, again screening for JA, but
      also including SA and one of its metabolic precursors, benzoic acid. We detected
      all three compounds in eggs of almost all the species examined. Moreover,
      concentrations of these compounds were variable across species, suggesting that
      species accumulate and/or utilize the compounds differently. Eggs of the fruit
      feeding fly Rhagoletis pomonella contained the greatest concentrations of all
      three compounds, which appear to be common in fruit. The presence of these plant
      derived compounds in eggs may serve defensive or other functions for insects, and
      could conceivably trigger plant defensive responses after oviposition.

PMID- 17191158
TI  - Learning from the 2001 anthrax attacks: immunological characteristics.

PMID- 17191159
TI  - Balancing maternal and infant benefits and the consequences of breast-feeding in
      the developing world during the era of HIV infection.

PMID- 17191160
TI  - Hepatitis C virus infection--its role in pathogenesis.

PMID- 17191161
TI  - Malaria vaccines based on the Plasmodium falciparum merozoite surface protein 3-
      should we avoid amino acid sequence polymorphisms or embrace them?

PMID- 17191162
TI  - The US capitol bioterrorism anthrax exposures: clinical epidemiological and
      immunological characteristics.
AB  - BACKGROUND: Bioterrorism-related anthrax exposures occurred at the US Capitol in
      2001. Exposed individuals received antibiotics and anthrax vaccine adsorbed
      immunization. METHODS: A prospective longitudinal study of 124 subjects-
      stratified on the basis of spore exposure, nasopharyngeal culture results, and
      immunization status from inside and outside an epidemiologically defined exposure
      zone--was performed to describe clinical outcome and immune responses after
      Bacillus anthracis exposure. Antibody and cell-mediated immune (CMI) responses to
      protective antigen (PA) and lethal factor were assayed by enzyme-linked
      immunosorbent assay and fluorescence-activated cell sorting. RESULTS: Antibody
      and CMI dose-exposure responses, albeit generally of low magnitude, were seen for
      unimmunized subjects from inside, within the perimeter, and outside the exposure
      zone and in nonexposed control subjects. Anti-PA antibody and CMI responses were
      detected in 94% and 86% of immunized subjects. No associations were seen between
      symptoms and exposure levels or immune responses. CONCLUSIONS: Anthrax spores
      primed cellular and possibly antibody immune responses in a dose-dependent manner
      and may have enhanced vaccine boost and recall responses. Immune responses were
      detected inside the perimeter and outside the exposure zone, which implies more
      extensive spore exposure than was predicted. Despite postexposure prophylaxis
      with antibiotics, inhalation of B. anthracis spores resulted in stimulation of
      the immune system and possibly subclinical infection, and the greater the
      exposure, the more complete the immune response. The significance of low-level
      exposure should not be underestimated.

PMID- 17191163
TI  - Mucosal delivery of a pneumococcal vaccine using Lactococcus lactis affords
      protection against respiratory infection.
AB  - BACKGROUND: Economical and effective vaccines against Streptococcus pneumoniae
      (pneumococcus) are needed for implementation in poorer countries where the
      disease burden is highest. Here, we evaluated Lactococcus lactis intracellularly
      producing the pneumococcal surface protein A (PspA) as a mucosal vaccine in
      conferring protection against pneumococcal disease. METHODS: Mice were
      intranasally (inl) immunized with the lactococcal vaccine. Control groups were
      also immunized with similar amounts of recombinant PspA administered inl or
      subcutaneously with alum. PspA-specific antibodies in serum samples and lung
      lavage fluids were measured before challenge in intraperitoneal sepsis and inl
      respiratory-infection models of pneumococcal disease. RESULTS: The lactococcal
      vaccine afforded better protection against respiratory challenge with
      pneumococcus than did vaccination with purified antigen given inl or by injection
      with alum. This finding was associated with a shift toward a Th1-mediated immune
      response characterized by reduced antibody titers to the PspA antigen. In the
      sepsis model, the lactococcal vaccine afforded resistance to disease on a par
      with that obtained with the injected vaccine, demonstrating its efficacy against
      different forms of pneumococcal disease. CONCLUSION: Given the safety profile of
      L. lactis, there is considerable potential to develop a pneumococcal vaccine for
      use in humans and to broaden this approach to combat other major pathogens.

PMID- 17191164
TI  - Isoniazid's bactericidal activity ceases because of the emergence of resistance,
      not depletion of Mycobacterium tuberculosis in the log phase of growth.
AB  - BACKGROUND: It is believed that the cessation of isoniazid's early bactericidal
      activity during the initial phase of antituberculosis therapy is due to the
      depletion of Mycobacterium tuberculosis in the exponential phase of growth. We
      examined the veracity of this cornerstone belief. METHODS: We used an in vitro
      infection model in which M. tuberculosis was exposed to isoniazid concentration
      time profiles encountered in human patients. Experiments were performed to
      examine the time-related changes in the total bacterial population, the isoniazid
      susceptible subpopulation, and the isoniazid-resistant subpopulation. RESULTS:
      The cessation of microbial kill occurred between days 3 and 4 of isoniazid
      therapy, as occurs in patients. There were multiple logs of organisms in the
      exponential phase of growth remaining at the time when bactericidal activity
      ceased. The isoniazid-susceptible subpopulation was replaced by an isoniazid
      resistant subpopulation after 80 h of therapy. The size of the isoniazid
      susceptible subpopulation continued to decrease after the total population had
      ceased to decrease, whereas the resistant subpopulation remained in the
      exponential phase of growth. Resistance was due to single point mutations in the
      catalase-peroxidase gene and to reserpine-inhibitable efflux pumps. CONCLUSIONS:
      The age-old hypothesis that isoniazid's microbial killing of M. tuberculosis
      during log-phase growth ceases because of the depletion of this bacillary
      population needs to be modified.

PMID- 17191165
TI  - Impact of antibiotics on expression of virulence-associated exotoxin genes in
      methicillin-sensitive and methicillin-resistant Staphylococcus aureus.
AB  - Extracellular protein toxins contribute to the pathogenesis of a wide variety of
      Staphylococcus aureus infections. The present study investigated the effects that
      cell-wall active antibiotics and protein-synthesis inhibitors have on
      transcription and translation of genes for Panton-Valentine leukocidin, alpha
      hemolysin, and toxic-shock syndrome toxin 1, in both methicillin-sensitive and
      methicillin-resistant S. aureus. Subinhibitory concentrations of nafcillin
      induced and prolonged mRNA for Panton-Valentine leukocidin, alpha-toxin, and
      toxic-shock syndrome toxin 1 and increased toxin production. In contrast,
      clindamycin and linezolid markedly suppressed translation, but not transcription,
      of toxin genes. These results suggest (1) that protein-synthesis inhibition is an
      important consideration in the selection of antimicrobial agents to treat serious
      infections caused by toxin-producing gram-positive pathogens and (2) that, by
      inducing and enhancing toxin production, inadvertent use of beta-lactam
      antibiotics to treat methicillin-resistant S. aureus infections may contribute to
      worse outcomes.

PMID- 17191166
TI  - Up-regulation of host cell genes during interferon-gamma-induced persistent
      Chlamydia pneumoniae infection in HL cells.
AB  - As a step toward understanding the role played by host gene expression in the
      development and pathogenesis of persistent Chlamydia pneumoniae infection,
      modulation of the host-cell transcriptional response during interferon (IFN)-
      gamma -induced persistent C. pneumoniae infection of HL cells was examined by a
      cDNA array and then selectively by a real-time quantitative reverse transcription
      polymerase chain reaction. We identified 9 host cell genes whose transcription
      was consistently altered during IFN- gamma -induced persistent C. pneumoniae
      infection. The strongest up-regulation of persistent infection, compared with
      controls (active infection and IFN- gamma ) was identified for insulin-like
      growth factor-binding protein 6, IFN-stimulated protein 15 kDa, cyclin D1, and
      interleukin-7 receptor genes. These results suggest that, during persistent
      infection, C. pneumoniae reprograms the host transcriptional machinery that
      regulates a variety of cellular processes, including adhesion, regulation of the
      cell cycle, growth, and inflammatory response, all of which might play important
      roles in the pathogenesis of persistent C. pneumoniae infection.

PMID- 17191168
TI  - Mortality in siblings of patients coinfected with HIV and hepatitis C virus.
AB  - BACKGROUND: Coinfection with hepatitis C virus (HCV) is a poor prognostic factor
      for human immunodeficiency virus (HIV)-infected patients. We examined whether the
      increased mortality in these patients is partly explained by a familial excess
      risk of death. METHODS: Danish HIV-infected patients who had had at least 1 HCV
      test were included (n=3531). In addition, 336,652 population control subjects
      matched for sex, age, and residency were identified from the Danish Civil
      Registration System. For both HIV-infected patients and population control
      subjects, we identified all siblings born after 1951, with dates of death or
      emigration. Siblings of HIV-infected patients were classified according to the
      patients' HCV serostatus. Survival after age 20 years was compared among the
      groups of siblings. RESULTS: We identified 437 siblings of HIV/HCV-coinfected
      patients, 1856 siblings of HIV-monoinfected patients, and 285,509 siblings of
      population control subjects. Mortality was substantially higher in siblings of
      HIV/HCV-coinfected patients than in either siblings of HIV-monoinfected patients
      (mortality rate ratio [MRR], 2.97 [95% confidence interval {CI}, 1.98-4.45]) or
      siblings of control subjects (MRR, 4.23 [95% CI, 3.09-5.79]). Siblings of HIV
      monoinfected patients had slightly higher mortality (MRR, 1.43 [95% CI, 1.10
      1.85]) than siblings of control subjects. CONCLUSIONS: HCV infection is a marker
      of familial factors that affect the survival of HIV-infected patients
      independently of the pathogenicity of HCV.

PMID- 17191167
TI  - HIV-1 disease progression in breast-feeding and formula-feeding mothers: a
      prospective 2-year comparison of T cell subsets, HIV-1 RNA levels, and mortality.
AB  - BACKGROUND: There is conflicting evidence regarding the effects of breast-feeding
      on maternal mortality from human immunodeficiency virus type 1 (HIV-1) infection,
      and little is known about the effects of breast-feeding on markers of HIV-1
      disease progression. METHODS: HIV-1-seropositive women were enrolled during
      pregnancy and received short-course zidovudine. HIV-1 RNA levels and CD4 cell
      counts were determined at baseline and at months 1, 3, 6, 12, 18, and 24
      postpartum and were compared between breast-feeding and formula-feeding mothers.
      RESULTS: Of 296 women, 98 formula fed and 198 breast-fed. At baseline, formula
      feeding women had a higher education level and prevalence of HIV-1-related
      illness than did breast-feeding women; however, the groups did not differ with
      respect to CD4 cell counts and HIV-1 RNA levels. Between months 1 and 24
      postpartum, CD4 cell counts decreased 3.9 cells/ microL/month (P<.001), HIV-1 RNA
      levels increased 0.005 log(10) copies/mL/month (P=.03), and body mass index (BMI)
      decreased 0.03 kg/m(2)/month (P<.001). The rate of CD4 cell count decline was
      higher in breast-feeding mothers (7.2 cells/ microL/month) than in mothers who
      never breast-fed (4.0 cells/ microL/month) (P=.01). BMI decreased more rapidly in
      breast-feeding women (P=.04), whereas HIV-1 RNA levels and mortality did not
      differ significantly between breast-feeding and formula-feeding women.
      CONCLUSIONS: Breast-feeding was associated with significant decreases in CD4 cell
      counts and BMI. HIV-1 RNA levels and mortality were not increased, suggesting a
      limited adverse impact of breast-feeding in mothers receiving extended care for
      HIV-1 infection.

PMID- 17191169
TI  - HIV-1 replication is stimulated by sodium stibogluconate, the therapeutic
      mainstay in the treatment of leishmaniasis.
AB  - Leishmaniasis is an important opportunistic disease among patients infected with
      human immunodeficiency virus (HIV)-1. The pentavalent antimony compound sodium
      stibogluconate is a drug of choice for the treatment of leishmaniasis. Because
      sodium stibogluconate acts as an inhibitor of phosphotyrosyl phosphatases and
      such inhibitors can promote HIV-1 replication, we tested the effect of this
      compound on virus gene expression. Using pseudotyped reporter viruses and fully
      infectious laboratory-adapted and clinical strains of HIV-1, we report that
      sodium stibogluconate induces an increase in HIV-1 transcription and virus
      replication in primary CD4(+) T cells and in thymic histocultures. This
      activation is a slow process and appears to involve the transcription factors
      nuclear factor- kappa B and activator protein 1, as well as the Syk, Jun, and
      mitogen-activated protein kinase/extracellular signal-related kinase signal
      transduction pathways. In addition, the effect seems to be partly mediated by a
      soluble factor. Altogether, these findings might reveal clinical implications for
      the treatment of leishmaniasis in HIV-1-infected patients.

PMID- 17191170
TI  - Viral gene expression in HIV transgenic mice is activated by Mycobacterium
      tuberculosis and suppressed after antimycobacterial chemotherapy.
AB  - We used human immunodeficiency virus (HIV) transgenic (Tg) mice incorporating the
      entire viral genome to study the effect of Mycobacterium tuberculosis infection
      on the induction of integrated HIV gene expression. When aerogenically infected
      with M. tuberculosis, these mice displayed a progressive increase in pulmonary
      gag and env mRNA levels and of p24 antigen production by cultured splenocytes. In
      situ hybridization of lungs revealed increased viral transcription associated
      with areas of inflammation and acid-fast bacilli. By neutralizing tumor necrosis
      factor (TNF) in vivo after M. tuberculosis exposure, we found that, although
      initially TNF independent, the increased HIV expression triggered by M.
      tuberculosis was highly dependent on this cytokine by 4 weeks after infection.
      Furthermore, treatment with antimycobacterial drugs markedly reduced HIV
      transgene expression. These studies establish an animal model for investigating
      the influence of M. tuberculosis on latent HIV expression and for testing
      therapeutic regimens for reducing the disease burden in patients with acquired
      immunodeficiency syndrome-associated tuberculosis.

PMID- 17191171
TI  - Expression profiling of peripheral-blood mononuclear cells from patients with
      chronic hepatitis C undergoing interferon therapy.
AB  - BACKGROUND: Interferon (IFN) is now the standard treatment for chronic hepatitis
      C (CH-C); however, treatment efficacy is unpredictable before IFN therapy is
      started. METHODS: We investigated the gene-expression profiles of peripheral
      blood mononuclear cells (PBMCs) from patients with CH-C showing different
      responses to IFN. Gene-expression profiles of PBMCs were analyzed in 21 patients
      with CH-C treated with IFN alone or in combination with ribavirin as well as in 6
      healthy volunteers. Serial changes in the gene-expression profiles of PBMCs from
      individual patients were evaluated before treatment, 2 weeks after the start of
      IFN therapy, and 6 months after the completion of IFN therapy. RESULTS:
      Interestingly, the gene-expression profiles of PBMCs from patients with CH-C and
      healthy volunteers differed substantially; early T cell-activation antigen CD69
      was significantly up-regulated in patients with CH-C, but immune-related
      molecules such as chemokine (C-C motif) receptor 2 and interleukin 7 receptor
      were significantly down-regulated. Selected combinations of expressed genes
      obtained before treatment and during IFN therapy by use of a fuzzy neural network
      combined with the SWEEP operator method predicted the outcome of IFN therapy with
      peak accuracies of 91.0% and 90.2%, respectively. CONCLUSIONS: These findings
      suggest that the gene-expression profiles of PBMCs from patients with CH-C may be
      useful biomarkers for IFN therapy.

PMID- 17191172
TI  - IL-7R alpha versus CCR7 and CD45 as markers of virus-specific CD8+ T cell
      differentiation: contrasting pictures in blood and tonsillar lymphoid tissue.
AB  - In humans, circulating CD8(+) memory T cells to a nonpersistent virus (influenza)
      lie within CCR7(+)CD45RA(-) central memory, whereas memory to Epstein-Barr virus
      (EBV) latent, EBV lytic, and cytomegalovirus (CMV) antigens are progressively
      larger in size and are more biased toward CCR7(-)CD45RA(-) effector memory and
      CCR7(-)CD45RA(+) terminally differentiated compartments. We found that these
      populations are also distinguished by progressively lower expression of the
      interleukin-7 receptor (IL-7R alpha) and by lower IL-7 responsiveness; indeed,
      percentage IL-7R alpha -positive values showed a tight inverse correlation with
      population size. However, these relationships among size, differentiation
      phenotype, and IL-7R alpha status in blood did not hold in tonsillar tissue. In
      tonsil tissue, although EBV reactivities outnumbered their CMV and influenza
      counterparts, the distinct CCR7/CD45 isoform signatures of the different virus
      specific populations were retained. Moreover, all detectable reactivities showed
      high levels of IL-7R alpha expression. As a discriminator between different virus
      specific populations, IL-7R alpha therefore appears to be more susceptible to
      tissue location than the classical CCR7/CD45 markers.

PMID- 17191173
TI  - Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific
      immunity and alleles are maintained by natural selection.
AB  - BACKGROUND: Plasmodium falciparum merozoite surface protein (MSP) 3 is an asexual
      blood-stage malaria vaccine candidate antigen. Sequence polymorphisms divide
      alleles into 2 major types, but the adaptive and immunological significance of
      the types has not been defined. METHODS: One hundred one msp3 allele sequences
      were sampled from 2 populations living in areas where malaria is endemic and were
      analyzed for evidence of natural selection. Recombinant antigens representing
      full-length sequences of different allelic types and a relatively conserved C
      terminal region were produced, to evaluate immunization-induced antibody
      responses in mice and protective associations for naturally acquired antibodies
      in a cohort of 319 Gambian children under surveillance for malaria. RESULTS:
      Frequency-based statistical analyses indicated that polymorphisms are maintained
      by balancing selection in each of the 2 populations studied. Immunization of mice
      with full-length MSP3 antigens induced predominantly type-specific antibodies,
      and a large proportion of naturally acquired antibodies to MSP3 in humans also
      discriminated between the alleles. Among Gambian children, antibodies to allele
      specific and conserved epitopes in MSP3 were associated prospectively with
      protection from clinical malaria, even after adjustment for age and for the
      presence of antibodies to other merozoite antigens. CONCLUSIONS: A vaccine
      incorporating both major allelic types of this promising candidate antigen could
      be particularly useful for induction of protective immunity in infants and young
      children.

PMID- 17191174
TI  - Th2 cytokines are associated with persistent hepatic fibrosis in human
      Schistosoma japonicum infection.
AB  - We conducted a prospective cohort study in Leyte, the Philippines, among 611
      Schistosoma japonicum-infected participants 7-30 years old, all of whom were
      treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal
      ultrasound was performed at baseline and 12 months after treatment. Stool for
      assessment of S. japonicum infection was collected at baseline and at 3, 6, 9,
      and 12 months after treatment. Cytokines (interleukin [IL]-4, IL-5, IL-10, IL-13,
      tumor necrosis factor- alpha , and interferon- gamma ) produced by peripheral
      blood mononuclear cells in response to soluble worm antigen preparation (SWAP),
      soluble egg antigen (SEA), and control medium were measured once 4 weeks after
      treatment. IL-4 to SWAP and IL-10 to both SWAP and SEA were associated with the
      presence of baseline fibrosis after adjustment for potential confounding
      variables (P<.03, for all). In participants with fibrosis at baseline, IL-4 to
      SWAP and IL-5 and IL-13 to both SWAP and SEA were associated with persistent
      fibrosis at 12 months after treatment (P<.05, for all). Males showed consistently
      stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did
      females (P<.02, for all). These results suggest an independent role for Th2
      biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis
      and indicate that Th2 cytokines may contribute to the male-biased prevalence of
      fibrosis.

PMID- 17191175
TI  - Immaturity of infection control in preterm and term newborns is associated with
      impaired toll-like receptor signaling.
AB  - The impaired infection control related to the functional immaturity of the
      neonatal immune system is an important cause of infection in preterm newborns. We
      previously reported that constitutive Toll-like receptor (TLR) 4 expression and
      cytokine secretion on lipopolysaccharide (LPS) stimulation increases with
      gestational age. Here, we analyzed constitutive monocyte TLR2 expression and
      evaluated the expression profiles of the proximal downstream adapter molecule
      myeloid differentiation factor 88 (MyD88). We further investigated activation of
      protein kinases p38 and extracellular regulated kinsase (ERK) 1/2 in CD14
      monocytes after ex vivo stimulation with bacterial TLR ligands (LPS and
      lipoteichoic acid [LTA]). The functional outcome of the stimulation was
      determined by cytokine secretion. Monocytes from 31 preterm newborns (<30 weeks
      of gestation, n=16; 30-37 weeks of gestation, n=15), 10 term newborns, and 12
      adults were investigated. In contrast to TLR4 expression, TLR2 levels did not
      differ between age groups. However, MyD88 levels were significantly lower in
      preterm newborns. Activation of p38 and ERK1/2 was impaired in all newborn age
      groups after stimulation with TLR-specific ligands. Accordingly, after LTA
      stimulation, the levels of interleukin (IL)-1 beta , IL-6, and IL-8 cytokine
      production were substantially lower (P<.001) in preterm newborns than in adults.
      The reduced functional response to bacterial cell wall components appears to be
      part of the functional immaturity of the neonatal immune system and might
      predispose premature newborns to bacterial infection.

PMID- 17191177
TI  - Correlates of sexually transmitted infections in young women.

PMID- 17191179
TI  - Diversity of community-associated strains of methicillin-resistant Staphylococcus
      aureus in Hawaii.

PMID- 17191180
TI  - Prototype misidentification makes conclusions about pathotype growth
      characteristics uncertain.

PMID- 17191182
TI  - The effects of artificial tear application on contrast sensitivity in dry and
      normal eyes.
AB  - PURPOSE: To investigate the effects of artificial tear application on contrast
      sensitivity in dry and normal eyes. METHODS: A total of 55 patients with normal
      (10/10) corrected or uncorrected visual acuity referring to GATA Gulhane Military
      Medical Academy Haydarpasa Ophthalmology Outpatient Clinic were evaluated in
      regard to dry eye diagnostic criteria, and assigned into the dry eye group (Group
      1; 35 patients) and the control group (Group 2; 20 patients). All patients were
      given a contrast sensitivity testing at low and high spatial frequencies using
      the gradual contrast sensitivity chart before and at 5 minutes after application
      of artificial tears, and the two groups were compared. Wilcoxon test was used in
      statistical analysis, accepting a p value of <0.05 as significant. RESULTS: In
      the dry eye group, there was a statistically significant increase in contrast
      sensitivity scores both at low and high frequencies after application of
      artificial tears (p<0.05). In the control group, although there was a significant
      increase in low frequency scores after artificial tear application (p< 0.05),
      there was not a significant change in high frequency scores (p>0.05).
      CONCLUSIONS: The decreased contrast sensitivity in dry eyes improves with
      application of artificial tears. Therefore, the impeded quality of vision seen in
      dry eye patients could be restored closer to normal with artificial tear therapy.
      Besides, contrast sensitivity testing could be used in the follow-up of
      artificial tear therapy.

PMID- 17191184
TI  - Evaluation of early corneal endothelial cell loss in bimanual microincision
      cataract surgery (MICS) in comparison with standard phacoemulsification.
AB  - PURPOSE: To analyze early corneal endothelial cell loss due to microincision
      cataract surgery (MICS) in comparison with standard phacoemulsification through
      the temporal clear corneal incision. METHODS: The examined group consisted of a
      nonrandomized, consecutive prospective series of 20 eyes of 20 patients who
      underwent uneventful microincision cataract surgery. Twenty eyes of 20 patients
      who underwent standard phacoemulsification with foldable intraocular lens (IOL)
      implantation served as a reference group. Patients with corneal disorders,
      contact lens wear, previous intraocular surgery, and a history of ocular trauma
      were excluded from the study. Patients were examined preoperatively and 10 days
      postoperatively. The following items were evaluated in this study: corneal
      endothelial cell density, intraoperative phaco power, effective phaco time, as
      well as pre- and postoperative visual acuity. Corneal endothelial cell counts
      were done in the central part of the cornea using a non-contact Topcon SP 2000P
      specular microscope before and 10 days after the surgery. The measurements were
      performed in a semiautomated, masked manner. Statistical analysis was done using
      nonparametric tests (Wilcoxon signed-ranks test and Mann-Whitney U test).
      RESULTS: All patients in the study underwent uneventful surgery. Best-corrected
      visual acuity (BCVA) examined 10 days postoperatively in the MICS group was
      0.94+/-0.094, whereas in the standard phacoemulsification group it was 0.90+/
      0.094. There was no significant difference between BCVA in the two groups (Mann
      Whitney U two-tailed test: p>0.05). In both groups there was a significant
      decrease in postoperative endothelial cell densities (ECDs) when compared to
      preoperative values. Mean postoperative ECDs were 2235+/-418 cells/mm2 in the
      MICS group and 2079+/-399 cells/mm2 in the standard phacoemulsification group;
      the difference was not statistically significant (Mann-Whitney U test: p>0.05).
      Patients in the MICS group lost an average of 9.5% of cells, whereas patients
      after standard phacoemulsification lost about 7.6% of cells. This difference was
      statistically insignificant. CONCLUSIONS: Microincision cataract surgery induced
      corneal endothelial cell loss similar to a standard phacoemulsification and
      allowed excellent visual results in this series of patients. These results
      support the use of MICS technique for cataract surgery.

PMID- 17191183
TI  - Rheumatoid keratolysis: a series of 40 eyes.
AB  - PURPOSE: Rheumatoid keratolysis (RK) is a rare but a serious cause of ocular
      morbidity in rheumatoid patients. The aim of this study was to analyze the
      presenting features, the subsequent treatment, and the outcome of patients with
      RK in the authors' department. METHODS: A retrospective study was undertaken of
      all patients with a diagnosis of RK at Bristol Eye Hospital between January 1987
      and June 2002. RESULTS: Forty eyes of 38 patients were identified in total. The
      mean age at presentation was 70 years. The mean duration of rheumatoid arthritis
      at presentation was 15 years. Most (22, 55%) ulcers were peripheral. Three
      patients (8%) developed RK within a month of cataract surgery. Out of the 19
      patients who did not have a further RK, 11 were immunosuppressed. A total of 37
      grafts were performed on 26 eyes. Twenty-two grafts (59%) failed.
      Immunosuppression increased the chance of anatomical success following
      penetrating keratoplasty. Infection was identified as a cause of graft failure
      for immunosuppressed patients in the postoperative period. Nine patients had
      reversible side effects from immunosuppressant treatment. Four eyes (10%) had to
      be surgically removed and a further 10 (25%) had severe visual loss (visual
      acuity less than 6/60). Eleven of the 38 patients subsequently died (29%
      mortality). CONCLUSIONS: Although the visual prognosis is often poor, surgical
      preservation of the eye can be achieved by penetrating keratoplasty and systemic
      immunosuppression. With careful observation and regular monitoring,
      immunosuppressive medication appears to be safely tolerated in this group of
      patients.

PMID- 17191185
TI  - Microincisional cataract surgery (MICS) with pulse and burst modes.
AB  - PURPOSE: To compare the amount of ultrasound (US) energy and balanced solution
      (BS) required for burst mode and pulse mode during bimanual phacoemulsification
      surgery. METHODS: One hundred cases were divided into two groups (the pulse mode
      Group 1 [50 eyes], the burst mode Group 2 [50 eyes]). One surgeon (M.B.)
      performed phaco notemulsification procedures using topical anesthesia with the
      AMO Sovereign in all patients. The technique was based on the nuclear hardness
      and surgeon's criteria and performed bimanually. The surgery time, total
      ultrasound time (UST) and effective US power (USP), and used balanced solution
      (BS) were retrospectively compared. RESULTS: The mean surgery time, mean UST, and
      mean used BS volume were not statistically different in both groups (p>0.05). The
      mean EPT was statistically highly different in both groups (p>0.001). There was a
      slight tendency toward more surgery time in Group 2 than in Group 1, although the
      difference was not significant (p=0.146). Statistically significant higher
      results (Group 1: r=0,889, p<0.001, and Group 2: r=0,834, p<0.001) were seen in
      Group 1 when both groups were evaluated for the surgery time and used BS volume.
      When UST and used BS volume were evaluated in Groups 1 and 2, significant
      relation was seen in both but the correlation is statistically higher in Group 1
      (Group 1: r=0,765, p<0.001, and Group 2: r=0,544, p<0.001). CONCLUSIONS: The very
      low energy modes with the WhiteStar technology are suitable for bimanual cataract
      surgery.

PMID- 17191186
TI  - New frontiers for the perioperative data method for IOL calculation following
      corneal refractive surgeries.
AB  - PURPOSE: To evaluate the efficiency of the perioperative data method for
      intraocular lens (IOL) calculation after correction of myopia and hyperopia with
      different techniques, including reoperated cases. METHODS: Thirty-five eyes (26
      patients) that developed cataract after corneal refractive procedures were
      evaluated retrospectively. They were categorized according to initial error of
      refraction into myopes and hyperopes and according to types of refractive
      procedures into ablative, incisional, both, or others. Reoperated cases were also
      considered. Number of refractive procedures was noted. Time interval between the
      first procedure and cataract extraction was indicated. Perioperative method was
      used to calculate the K value. SRK/T formula was used to calculate IOL power.
      Difference between intended and finally achieved manifest refraction was an
      indicator for efficiency of the calculation. RESULTS: Postoperatively, 77.2% of
      cases had manifest refraction +/-1.5 D of intended refraction. There was no
      difference between myopes and hyperopes in terms of final manifest refraction,
      best-corrected visual acuity, and difference between intended and finally
      achieved manifest refraction. Similarly were groups of different types of
      surgeries. Efficiency of the method decreased with high axial lengths and low IOL
      powers. Neither the number of refractive surgeries nor time interval between
      surgeries affected efficiency of the method. CONCLUSIONS: The perioperative data
      method is equally effective for myopes and hyperopes. The types, numbers of
      refractive procedures, as well as the time interval between refractive surgery
      and cataract extraction do not alter the credibility of the method. In high
      degrees of myopia, the method gives less accurate results.

PMID- 17191188
TI  - Verteporfin therapy and triamcinolone acetonide: convergent modes of action for
      treatment of neovascular age-related macular degeneration.
AB  - PURPOSE: Choroidal neovascularization associated with age-related macular
      degeneration is the primary cause of blindness in the elderly in developed
      countries, due to a number of pathogenic effects, including angiogenesis, cell
      mediated inflammation, leukocyte adhesion and extravasation, and matrix
      remodeling. METHODS: By producing photochemical effects at the site of target
      tissue (lesion), photodynamic therapy (PDT) can induce vascular damage and blood
      flow stasis, leading to occlusion of vascularization and lesion leakage. RESULTS:
      PDT with verteporfin (Visudyne, Novartis) has been shown to be safe and effective
      in reducing the risk of vision loss in patients with classic containing subfoveal
      CNV and occult with no classic CNV. However, in predominantly occult CNV, the
      treatment may be most effective in smaller lesions, and less in larger lesions.
      Most important, visual acuity rarely is improved. CONCLUSIONS: Pilot studies and
      large case series suggest that a combination of PDT and intravitreal
      triamcinolone acetonide has the potential to improve visual outcomes and reduce
      the need for additional treatments. Randomized, prospective clinical trials are
      underway to confirm the efficacy and safety of this novel treatment modality.

PMID- 17191187
TI  - The efficacy and safety of timolol maleate versus brinzolamide each given twice
      daily added to travoprost in patients with ocular hypertension or primary open
      angle glaucoma.
AB  - PURPOSE: To compare the efficacy and safety of timolol maleate 0.5% versus
      brinzolamide 1% when added to travoprost 0.004% in patients with ocular
      hypertension or primary open-angle glaucoma. DESIGN: A prospective, double
      masked, randomized, active-controlled, parallel comparison. METHODS: Qualified
      patients at Visit 1 were placed on travoprost dosed every evening for 4 weeks and
      then were randomized at baseline (Visit 2) to the addition of timolol maleate or
      brinzolamide each given twice daily. Patients returned to clinic at Week 4 (Visit
      3) for a safety visit and Week 12 (Visit 4) for an efficacy visit. At Visits 2
      and 4 the intraocular pressure (IOP) was measured at 08:00, 12:00, and 16:00
      hours. RESULTS: Ninety-seven patients on brinzolamide had a baseline diurnal IOP
      of 21.5+/-2.2 mmHg and 95 on timolol maleate had 21.3+/-2.5 mmHg, each added to
      travoprost. The diurnal mean IOP at Week 12 was 18.1+/-2.7 mmHg for brinzolamide
      and 18.1+/-3.0 mmHg for timolol maleate (p=0.96). There was no statistical
      difference found between treatment groups in the absolute level of pressure, or
      in the reduction in IOP from baseline, at each time point or for the diurnal
      curve (p>0.05). There was no significant difference for any adverse event between
      groups (p>0.05), with the most common side effect being conjunctival hyperemia in
      15/97 (16%) brinzolamide and 6/95 (6%) timolol treated patients (p=0.06).
      CONCLUSIONS: This study showed that brinzolamide provides similar safety and
      efficacy compared to timolol maleate when added to travoprost.

PMID- 17191189
TI  - Secondary management and outcome of massive suprachoroidal hemorrhage.
AB  - PURPOSE: To present the results of secondary surgical treatment of five patients
      with massive suprachoroidal hemorrhage (MSCH), which occurred intraoperatively,
      postoperatively, or following ocular trauma. METHODS: Five patients presenting
      with MSCH were included in this study during or after phacoemulsification surgery
      (1 patient), glaucoma surgery (1 patient), combined glaucoma and
      phacoemulsification surgery (2 patients), and after traumatic sclera rupture (1
      patient). Diagnosis was confirmed by ophthalmoscopy and B-scan ultrasonography.
      Pre-existing risk factors and distance visual acuity were documented. All cases
      received medical therapy and underwent secondary surgical intervention with
      radial sclerotomies combined with vitrectomy, use of perfluorocarbon, and
      silicone oil. Postoperative assessment included visual acuity measurement, ocular
      examination, and ultrasonography. RESULTS: In all cases, anatomic restoration of
      ocular structures was achieved. Distance visual acuity improved in all cases
      (preoperative Snellen visual acuity ranged from light perception to hand motions;
      postoperative Snellen visual acuity ranged from 0.05 to 0.3). The mean follow-up
      period was 17 months. CONCLUSIONS: In general, despite the advanced surgical
      techniques, the prognosis of MSCH remains guarded and the visual outcome poor.
      However, secondary surgical treatment with combined radial sclerotomies and
      vitrectomy should be considered in order to minimize the damaging effect and
      maximize the anatomic and functional restoration.

PMID- 17191190
TI  - Long-term visual outcomes of vitrectomy for cystoid macular edema due to
      nonischemic central retinal vein occlusion.
AB  - PURPOSE: To report the long-term surgical outcome of vitrectomy for cystoid
      macular edema due to nonischemic central retinal vein occlusion (CRVO). METHODS:
      A retrospective chart review of 25 consecutive eyes (25 patients) with cystoid
      macular edema due to nonischemic CRVO treated with vitrectomy was performed. All
      patients underwent a pars plana vitrectomy with the creation of a posterior
      vitreous detachment if still attached. Simultaneous phacoemulsification with
      intraocular lens implantation was also performed in phakic eyes. The main outcome
      measures were best-corrected visual acuity (BCVA) and changes in macular edema
      shown by contact-lens biomicroscopy. The mean follow-up time was 49 months
      (range, 16-108). RESULTS: The median BCVA before surgery was 0.31 and the median
      BCVA at last follow-up was 0.67. The BCVA at the last follow-up improved at least
      two Snellen lines in 17 (68%), remained unchanged in 4 (16%), and worsened in 4
      (16%). The BCVA was 20/40 or better in 3 eyes (12%) preoperatively and in 18 eyes
      (72%) at the last follow-up. During the follow-up, four patients progressed to
      ischemic CRVO; one of them had neovascular glaucoma requiring surgical
      intervention. CONCLUSION: The data indicate that vitrectomy appears to be a
      possibly effective treatment in some eyes with cystoid macular edema associated
      with nonischemic CRVO.

PMID- 17191191
TI  - Long-term outcome after conservative treatment of indirect traumatic optic
      neuropathy.
AB  - PURPOSE: To report the long-term outcome of patients with indirect traumatic
      optic neuropathy (TON) which showed useful vision for a short period after
      trauma. METHODS: A cohort of 12 TON patients treated with steroids megadose
      immediately after trauma was followed every 6 months for an overall period of 5
      years. Other than a full neuro-ophthalmologic examination, each visit included
      quantitative Goldmann perimetry and pattern reversal visual evoked potentials.
      The results of each examination were compared with the visual function at
      baseline. The main outcome measures were visual acuity and visual field. Data
      were analyzed using the Wilcoxon signed-rank test. A p value of less than 0.05
      was considered statistically significant. RESULTS: All patients showed a stable
      visual function 5 years after optic nerve trauma. There was no difference in
      visual acuity levels (p=0.65) and no visual field surface area between the visit
      at baseline and the last follow-up. However, a significant improvement in visual
      field extension (p=0.036) was observed after perimetry evaluation. CONCLUSIONS:
      This cohort of patients clearly demonstrates that the residual visual function
      found in the short term after TON is maintained for at least 5 years. These
      findings add further important clinical information for patients with TON.
      Furthermore, these data may be helpful to better quantify morbidity related to
      optic nerve trauma and its permanent sequelae.

PMID- 17191193
TI  - Controlling blepharospasm effect during applanation tonometry using the Volk
      SuperField Lid Lens Adapter.
AB  - PURPOSE: To describe a practical clinical technique that can be used to control
      the effect of blepharospasm during applanation tonometry. METHODS: The Volk
      Superfield NC Lid Lens Adapter is used to keep the eye open and prevent the
      squeezing effect of orbicularis oculi in blepharospasm. RESULTS: This helpful
      tool can be used when blepharospasm becomes a problem that interferes with
      accurate intraocular pressure measurement. CONCLUSIONS: The technique is
      potentially useful and relatively easy to perform.

PMID- 17191192
TI  - Quality of vision: A consensus building initiative for a new ophthalmologic
      concept.
AB  - PURPOSE: Many studies have addressed the quantification of visual acuity, and the
      conventional method of measuring it has so far demonstrated serious limitations.
      Vision testing requires new methods that can more precisely express the quality
      of vision as perceived by the patient. METHODS: This study employed the Delphi
      method of consensus building. Concepts associated with quality of vision (QoV)
      were identified by a board of experts and proposed to participating specialists
      in two subsequent questionnaires. Upon receipt of the completed questionnaires,
      the replies were classified to determine the building blocks of a consensus.
      RESULTS: By analyzing the replies to the two questionnaires, the authors
      determined the key elements of QoV on which a consensus was found among the
      respondents. CONCLUSIONS: A consensus was reached on the opinion that the
      quantification of visual acuity by traditional means is inadequate for
      investigating QoV. Although visual acuity is still a basic element for testing,
      the experts believe that contrast sensitivity, reading speed, and microperimetry
      are additional parameters necessary for quantifying QoV. The use of a
      psychometric questionnaire on visual function could allow a better interpretation
      of visual impairment.

PMID- 17191194
TI  - Prevalence of congenital optic disc pits in adult Chinese: The Beijing Eye Study.
AB  - PURPOSE: To determine the prevalence of optic disc pits in the elderly Chinese
      population. METHODS. The Beijing Eye Study, a population-based, cross-sectional
      cohort study, included 4439 subjects out of 5324 subjects invited to participate
      (response rate 83.4%) with an age of 40+ years. The present study included 4027
      (90.7%) subjects for whom readable optic disc photographs were available.
      RESULTS: A pit of the optic nerve head was detected in one (0.02%) patient.
      Prevalence was 0.02 +/-1.58% (95% confidence interval: -0.02, 0.07). CONCLUSIONS:
      A congenital optic disc pit was found in one subject of the present population
      based study in mainland China. In a mathematical sense, the calculated prevalence
      of optic disc pits in the whole population would be 0.02 +/- 1.58% (95%
      confidence interval: -0.02, 0.07) or about 1:4.000 subjects. From a statistical
      point of view, however, population-based studies with about 10,000 subjects are
      necessary to confirm this finding.

PMID- 17191196
TI  - Ocular involvement in anti-epiligrin cicatricial pemphigoid.
AB  - PURPOSE: To report an anti-epiligrin cicatricial pemphigoid (AECP) patient with
      severe ocular involvement and to provide a practical approach to distinguishing
      AECP patients from those with other subepidermal blistering diseases. METHODS:
      Techniques included direct and indirect immunofluorescence microscopy, Western
      blot and immunoprecipitation studies, as well as interdisciplinary examinations
      of mucous membranes and skin. RESULTS: This study describes a patient with
      clinical features of cicatricial pemphigoid, circulating anti-basement membrane
      zone IgG antibodies, and subepidermal blisters. Histopathology and
      immunofluorescence analysis suggested the diagnosis of a cicatricial pemphigoid
      like type of epidermolysis bullosa acquisita. However, Western blot and
      immunoprecipitation studies demonstrated that the patient's serum contained
      autoantibodies against laminin 5 alpha3 subunit, leading to the diagnosis of an
      AECP. CONCLUSION: Since patients with AECP have an increased relative risk for
      malignant tumors, it is important to distinguish this entity within the spectrum
      of cicatricial pemphigoid patients by additional studies such as Western blot or
      immunoprecipitation.

PMID- 17191197
TI  - Limbal stem cell deficiency in the context of autoimmune polyendocrinopathy.
AB  - PURPOSE: To report two sisters with bilateral progressive visual loss and
      photophobia secondary to stem cell deficiency due to multiple endocrine
      deficiency. METHODS: Case reports and review of medical literature. RESULTS: The
      younger sister had severe photophobia and decreased visual acuity since May 2000.
      Despite multiple outpatient visits no definite cause was found and conservative
      treatments failed. On slit lamp examination severe meibomian gland dysfunction,
      loss of eyelashes, decreased tear meniscus, diffuse corneal vascularization, and
      delayed punctate fluorescein staining of corneal epithelium were detected. She
      also had episodes of hypotension, oral candidiasis, and seizures. Her systemic
      workup revealed multiple endocrine deficiency (Addison's disease and
      hypoparathyroidism). Hormone replacement therapy with fludrocortisone and oral
      calcium accompanied by punctual occlusion led to significant clinical recovery .
      The older sister showed a similar pattern but interestingly the onset was later
      and the signs and symptoms were milder. CONCLUSIONS: In the pediatric age group
      with diffuse corneal vascularization and no definite cause, systemic workup
      should be done to rule out multiple endocrine deficiencies. The therapy consists
      of hormone replacement therapy and management of dry eye.

PMID- 17191195
TI  - Prevalence of retinitis pigmentosa in urban and rural adult Chinese: The Beijing
      Eye Study.
AB  - PURPOSE: To determine the prevalence of retinitis pigmentosa in the elderly
      Chinese population. METHODS: The Beijing Eye Study is a population-based, cross
      sectional cohort study and included 4439 subjects out of 5324 subjects invited to
      participate (response rate 83.4%) with an age of 40+ years. Readable fundus
      photographs were available for 4027 (90.7%) subjects. Diagnostic criteria for
      retinitis pigmentosa were visual field defects on frequency doubling perimetry,
      typical ophthalmoscopic abnormalities such as retinal pigment deposits, retinal
      arteriole attenuation, and pigment epithelial atrophy, and no other reason for
      perimetric defects and fundus abnormalities. RESULTS: Retinitis pigmentosa was
      diagnosed in four subjects (all men). Its prevalence was 0.099+/-3.15% (95% CI:
      0.00, 0.2). CONCLUSIONS: Retinitis pigmentosa with typical fundus appearance and
      functional loss may be present in about 1 out of 1000 elderly Chinese in Northern
      China. Calculated for the whole population in China, the figure would be 1.3
      million patients with retinitis pigmentosa.

PMID- 17191199
TI  - Delayed treatment of choroidal melanoma due to pregnancy.
AB  - PURPOSE: The authors report a 27-year-old woman who presented with a large,
      choroidal melanoma when she was 28 weeks pregnant. Following detailed discussion
      with the patient, the decision was made to postpone any surgical treatment until
      after the birth of her child. METHODS: Case report. RESULTS: The patient had
      successful transscleral local resection of the tumor with 6/12 vision 6 months
      later. Cytogenetic studies showed a low risk of subsequent metastases.
      CONCLUSIONS: This case illustrates that deferring the treatment of a choroidal
      melanoma presenting during pregnancy can be a reasonable treatment plan, if the
      patient is highly motivated to keep the eye.

PMID- 17191198
TI  - Iris melanocytoma mimicking the Cogan-Reese syndrome with monocular pigment
      dissemination.
AB  - PURPOSE: To report a case of iris melanocytoma mimicking the Cogan-Reese
      syndrome. METHODS: A 37-year-old woman presented with pigmentary glaucoma in her
      left eye. There was diffuse pigmentary dispersion in the anterior segment,
      pedunculated pigmented nodules on the anterior iris surface, mild iris atrophy,
      and ectropion iridis. Neither intrinsic vasculature nor a sector cataract was
      found. The angle was open with marked trabecular pigmentation and no anterior
      synechiae. The intraocular pressure was 30 mmHg with maximum medical treatment
      and there was glaucomatous optic atrophy. The differential diagnosis included
      iris pigmented tumor and iridocorneal endothelial syndrome (Cogan-Reese
      syndrome). An iris biopsy was performed for diagnostic purposes. RESULTS:
      Histologic diagnosis after evaluation of the specimen was iris melanocytoma.
      CONCLUSIONS: This case presents signs considered quasi-pathognomonic of
      iridocorneal endothelial syndrome (Cogan-Reese syndrome): glaucoma, mild iris
      atrophy associated with pedunculated iris nodules, and ectropion iridis.
      Therefore, iris melanocytoma can present with features that mimic the Cogan-Reese
      syndrome.

PMID- 17191200
TI  - Bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy:
      a report of three cases.
AB  - PURPOSE: To report three cases of bilateral primary choroidal melanoma treated
      with bilateral plaque radiotherapy. METHODS: Retrospective, single-center case
      series. RESULTS: Case 1: In 1981, a 50-year-old man was diagnosed with a 5-mm
      thick choroidal melanoma in the right eye (OD) and treated with plaque
      radiotherapy. In 1994, a 6.8-mm-thick choroidal melanoma in the left eye (OS) was
      treated with plaque radiotherapy. Final visual acuity was light perception OD and
      20/20 OS at 24 years follow-up. Case 2: In 1983, a 53-year-old woman was
      diagnosed with a 3.5-mm-thick choroidal melanoma OS and treated with plaque
      radiotherapy. In 2001, an enlarging 2.5-mm-thick choroidal melanoma OD was
      treated with plaque radiotherapy. Final visual acuity was 20/30 OD and 20/20 OS
      at 22 years follow-up. Case 3: In 2001, a 92-year-old man was diagnosed with a
      7.9-mm-thick choroidal melanoma OD treated with plaque radiotherapy. In 2003, an
      enlarging 2.8-mm-thick juxtapapillary choroidal melanoma was treated with plaque
      radiotherapy. Final visual acuity was 20/70 OD and 20/60 OS at 2.5 years follow
      up. No patient showed ocular melanocytosis. Stable tumor regression was achieved
      in all six eyes. Metastatic disease did not develop in any case over 16 years of
      follow-up. CONCLUSIONS: Monitoring of both eyes of patients with uveal melanoma
      is important for the remote possibility of melanoma in the second eye. In these
      three patients, plaque radiotherapy allowed for preservation of the globes and
      some vision.

PMID- 17191201
TI  - Optical coherence tomography and focal electroretinogram evaluation of cystoid
      macular edema secondary to retinitis pigmentosa treated with intravitreal
      triamcinolone: case report.
AB  - PURPOSE: To assess macular structure and function by optical coherence tomography
      (OCT) and focal electroretinogram (FERG) before and after intravitreal
      triamcinolone acetonide (IVTA) administration for cystoid macular edema (CME) in
      a patient with retinitis pigmentosa (RP). METHODS: A 33-year-old man with RP and
      refractory bilateral macular edema was treated with IVTA in his left eye and
      evaluated with visual acuity, OCT, and FERG for 6 months. RESULTS. Compared to
      the fellow eye, after IVTA mean retinal thickness significantly decreased, while
      FERG amplitude and phase did not show significant changes at the end of follow
      up. Visual acuity showed a significant tendency to improve. CONCLUSIONS: In this
      case report, IVTA improved macular anatomy and visual acuity; this result,
      however, was not associated with a similar electrophysiologic response.

PMID- 17191203
TI  - Sympathetic ophthalmia after successful retinal reattachment surgery with
      vitrectomy.
AB  - PURPOSE: To report a case of sympathetic ophthalmia (SO) following one successful
      pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment. METHODS: Case
      report. RESULTS: A 50-year-old man developed SO 5 weeks after successful repair
      of rhegmatogenous retinal detachment with PPV and intraocular gas tamponade. The
      patient presented with bilateral multifocal exudative retinal detachments and
      inflamed optic nerve with characteristic changes of SO detected by fluorescein
      angiography, indocyanine green angiography, and optical coherence tomography.
      Prompt use of systemic steroids and cyclosporin A resulted in control of the
      uveitis with significant visual improvement. CONCLUSIONS: PPV should be viewed as
      a major risk factor for development of SO.

PMID- 17191202
TI  - Immunohistochemical findings in epiretinal membrane after long-term silicone oil
      tamponade: case report.
AB  - PURPOSE: To report pre- and post-operative macular optical coherence tomography
      (OCT) and immunohistochemical findings in a case of long-lasting silicone oil
      tamponade followed by silicone oil removal and epimacular membrane peeling.
      METHODS: A 69-year-old man with long-standing silicone oil tamponade and an
      epiretinal membrane at the posterior pole in his right eye (RE) underwent
      silicone oil/BSS exchange with epiretinal membrane peeling. Preoperatively, RE
      best-corrected visual acuity was 20/200 and macular OCT examination revealed a
      small increase in foveal thickness (250 microm) with the appearance of a linear
      hyper-reflective signal at the foveal vitreoretinal interface and a thicker (440
      microm) hyperreflective finding causing posterior shadowing at the vitreoretinal
      interface inferiorly to the fovea. Histopathologic and immunohistochemical study
      of the specimen including the epiretinal membrane was performed. RESULTS: Light
      microscopy revealed extensive rounded empty spaces interpreted as silicone oil
      bubbles in the preretinal membrane. Macrophages marker (CD68) positive staining
      cells were found surrounding the empty spaces within the preretinal membrane and
      several empty spaces were observed intracellularly within macrophage cytoplasm.
      Thirty days after surgery best-corrected visual acuity was 20/60 and OCT
      examination showed an evident decrease in foveal thickness (220 microm) with the
      disappearance of any hyper-reflective signal at the vitreoretinal interface
      referable to an epiretinal membrane. CONCLUSIONS: The immunohistochemical study
      showed both silicone oil droplets and macrophagic cells embedded in the
      epiretinal membrane. Postoperative OCT demonstrated retinal recovery after
      silicone oil removal and epiretinal membrane peeling, thus justifying an
      unexpected visual acuity recovery despite the very long term tamponade.

PMID- 17191205
TI  - Truncation of NHEJ1 in a patient with polymicrogyria.
AB  - Polymicrogyria (PMG) is a common malformation of the human cerebral cortex for
      which both acquired and genetic causes are known. Although genetic heterogeneity
      is documented, only one gene is currently known to cause isolated PMG. To clone
      new genes involved in this type of cerebral malformation, we studied a fetus
      presenting a defect of cortical organization consisting of a polymicrogyric
      cortex and neuronal heterotopia within the white matter. Karyotype analysis
      revealed that the fetus was carrier of a balanced, de novo, chromosomal
      translocation t(2;7)(q35;p22). Cloning and sequencing of the two translocation
      breakpoints reveals that the chromosomal rearrangement disrupts the coding region
      of a single gene, called NHEJ1, Cernunnos, or XLF, in 2q35. The NHEJ1 gene was
      recently identified as being responsible for autosomal recessive immunodeficiency
      with microcephaly. Using quantitative PCR experiments, we show that a truncated
      transcript is expressed in the polymicrogyric patient cells, suggesting a
      potential dominant negative effect possibly leading to a different phenotype. We
      performed in situ hybridization on human embryos and showed that the NHEJ1
      transcript is preferentially expressed in the telencephalic ventricular and
      subventricular zones, consistent with the phenotype of the affected individual.
      In the human adult central nervous system (CNS), NHEJ1 is mainly expressed in the
      cerebral cortex and in the cerebellum. The association of PMG with the disruption
      of its transcript suggests that, in addition to its recently uncovered function
      in the immune system, the NHEJ1 protein may also play a role during development
      of the human cerebral cortex.

PMID- 17191204
TI  - Primary localized orbital amyloidosis: a case report.
AB  - PURPOSE: Amyloidosis refers to a heterogeneous group of disorders associated with
      deposition of chemically distinct fibril proteins. Isolated orbital amyloidosis
      is a rare condition and requires systemic examination. The authors report a case
      of amyloid deposit in the orbit whose systemic investigation has been negative.
      METHODS: A 64-year-old woman presented to the eye clinic with left-sided orbital
      mass, mild exophthalmos with downward ocular displacement, and ptosis. The
      patient presented also visual acuity loss and ocular hypertension. No systemic
      involvement was noted by systemic workup and it confirmed the primary orbital
      amyloidosis. RESULTS: The patient was subject to full clinical examination,
      laboratory examinations, orbital echography, magnetic resonance imaging and total
      body computed tomography scans, rectal mucosa, and temporal artery biopsies. It
      was necessary to exclude systemic amyloidosis. The presence of amyloid deposits
      was confirmed by biopsy of orbital mass. The chemical nature of deposit was
      characterized using light microscopy, immunohistochemistry, and electron
      microscopy. CONCLUSIONS: Orbital amyloidosis is a very rare disease. It should be
      considered in the diagnosis of patients with ptosis and exophthalmos. The
      treatment usually consists of surgical removal of the amyloid mass and follow-up
      for a likely local recurrence. In our case, mass excision determined the decrease
      of exophthalmos and intraocular pressure.

PMID- 17191209
TI  - Balloon versus metal for percutaneous mitral commissurotomy.

PMID- 17191206
TI  - Impact of renal insufficiency on clinical and angiographic outcomes following
      percutaneous coronary intervention with sirolimus-eluting stents.
AB  - BACKGROUND: Sirolimus-eluting stents (SES) have been demonstrated to reduce
      restenosis. However, there have been few studies evaluating the impact of renal
      insufficiency on the angiographic as well as clinical outcomes after SES
      implantation. METHODS: This study was composed of 304 consecutive patients having
      361 lesions who underwent percutaneous coronary intervention with SES. The
      patients were divided into 3 groups according to renal function (group 1 [n =
      204]; creatinine clearance (Ccr) > or = 60 ml/min, group 2 [n = 69]; Ccr < 60
      ml/min, group 3 [n = 31]; hemodialysis). Clinical and angiographic follow-up were
      evaluated at 8 months. RESULTS: Clinical follow-up was obtained in all patients
      and angiographic follow-up was obtained in 283 patients (93.1%). Patients in
      group 3 showed a higher incidence of previous coronary artery bypass graft
      surgery, and there were more female gender, hypertensive, and less hyperlipidemia
      in this group. Late lumen loss at 8 months was significantly different among the
      3 groups (group 1; 0.16 +/- 0.46 mm, group 2; 0.44 +/- 0.62 mm, group 3; 0.81 +/-
      0.88 mm, P < 0.0001). Major adverse cardiac events (MACE) were documented in 22
      patients (10.8%) in group 1, 13 patients (18.8%) in group 2, and 12 patients
      (38.7%) in group 3, respectively (P = 0.0002). CONCLUSION: Neointimal growth
      following SES implantation is more pronounced in patients with renal
      insufficiency, especially those undergoing dialysis, compared with patients with
      normal renal function. Regardless of the beneficial effect of SES, the increased
      risk of MACE mainly due to high incidence of target vessel revascularization in
      the subgroup of patients with renal insufficiency should be taken into account.

PMID- 17191207
TI  - Stent fracture: an unusual cause of late restenosis after sirolimus-eluting stent
      placement.
AB  - Stent fracture is uncommon but may have consequences including restenosis. To
      date, stent fractures reported have been related to aggressive post dilation. We
      describe a case that involves fracture of a stent deployed to nominal pressure.
      Unlike most stent fractures reported that involve stent struts only our case
      demonstrated circumferential disruption with complete separation of the stent
      segments.

PMID- 17191210
TI  - Percutaneous coronary intervention of a circumflex chronic total occlusion using
      an epicardial collateral retrograde approach.
AB  - Antegrade disobliteration of a chronic total coronary occlusion (CTO) may be
      technically difficult in spite of the use of customized equipment. Retrograde
      approaches via intramyocardial septal or bypass grafts have been described. We
      report a successful Percutaneous intervention of a proximal circumflex CTO using
      a retrograde approach via an epicardial collateral.

PMID- 17191211
TI  - Factors predictive of cardiac events and restenosis after sirolimus-eluting stent
      implantation in small coronary arteries.
AB  - OBJECTIVES: Predictors of cardiac events and restenosis after sirolimus-eluting
      stent (SES) implantation in small coronary arteries were evaluated. BACKGROUND:
      Although SES implantation has markedly reduced the risk of restenosis, small
      vessel disease remains a major cause of SES failure. METHODS: We prospectively
      investigated the factors predictive of cardiac events and restenosis in 1,092
      consecutive patients who received SES implantation for 1,269 lesions in small
      coronary arteries (< or = 2.8 mm). Follow-up angiography at 6 months was
      performed in 751 patients with 889 lesions (follow-up rate 70.3%). RESULTS:
      Restenosis (diameter stenosis > or = 50%) was angiographically documented in 65
      patients with 77 lesions (8.7%): 55 focal (71.4%), 8 diffuse (10.4%), 2 diffuse
      proliferative (2.6%), and 12 total (15.6%). Lesion length, stent length,
      reference artery size, and in-stent restenotic lesions were univariate predictors
      of restenosis. By multivariate analysis, lesion length (OR 1.04; 95% CI 1.02
      1.05; P < 0.001) and in-stent restenotic lesions (OR 3.38; 95% CI 1.80-6.35; P <
      0.001) were significant independent predictors of restenosis. During follow-up
      (23.2 +/- 7.9 months), there were 17 deaths (5 cardiac and 12 noncardiac), 5
      nonfatal Q-wave myocardial infarctions, and 42 target lesion revascularizations.
      The cumulative probability of survival without major adverse cardiac events
      (MACE) was (96.6 +/- 0.6)% at 1 year and (95.1 +/- 0.7)% at 2 years. In
      multivariate analysis, lesion length (HR 1.04; 95% CI 1.01-1.07; P = 0.004) and
      in-stent restenotic lesions (HR 3.29; 95% CI 1.58-6.86; P = 0.001) were
      independently related to MACE. CONCLUSIONS: SES implantation in small coronary
      arteries is safe and effective, with lesion length having a major impact on
      restenosis and MACE.

PMID- 17191212
TI  - Magnetic navigation system used successfully to cross a crushed stent in a
      bifurcation that failed with conventional wires.
AB  - Bifurcation lesions can be technically demanding to manage, and even in the era
      of drug eluting stents, their procedural success is variable. The use of the
      crush technique followed by "kissing" balloon postdilatation has been shown to
      improve the overall outcome. However, crossing the crushed stent is essential to
      allow performance of a final dilatation with "kissing" balloons and is regarded
      as the main Achilles' heel of this technique. In this report, we describe the
      first reported, planned procedure to use a magnetic navigation system to steer a
      wire through the crushed stent to use "kissing" balloons that had previously
      failed with conventional wires.

PMID- 17191213
TI  - Transcatheter closure of secundum atrial defect in small children.
AB  - OBJECTIVE: To assess safety and efficacy of transcatheter atrial septal defect
      (ASD) closure in small children. BACKGROUND: Percutaneous closure of ASD is a
      well accepted alternative to surgery. Reported experience in small children
      remains, however, scarce. METHODS: Fifty-two children underwent percutaneous ASD
      closure at a weight < or =15 kg, in four Belgian tertiary referral paediatric
      cardiology centers. Indication for treatment, device implantation rate,
      procedural details, complication rate, residual shunt on echocardiography, and
      impact of procedure on symptoms were retrospectively analyzed. RESULTS: Mean age
      at procedure was 36 months (7-60), mean weight 13 kg (4.7-15). Associated cardiac
      lesions were seen in 21% of the patients and noncardiac in 32.7%. Most patients
      (69.2%) were symptomatic. Mean ASD size was 12 mm (range 5-20 mm). A device could
      be inserted in 49 patients (94%). No major complications occurred. Minor
      complications occurred in 8 patients (15.4%) including device embolization in 2,
      successfully treated with transcatheter retrieval and second device insertion.
      Mean follow-up reached 27 months (0.03-61.2). Residual shunt was absent, trivial,
      or small in 93% (n = 42) at latest follow-up. Clinical improvement was noted in
      91.7% of the symptomatic patients. Minor complications were more frequent in the
      presence of large ASDs (>15 mm) but not in smaller babies (<10 kg). CONCLUSION:
      Patients < or =15 kg requiring ASD closure form a special population with high
      incidence of associated anomalies and medical conditions. For this particular set
      of patients, percutaneous closure is a valid alternative. Asymptomatic or mildly
      symptomatic children should be treated at a later age.

PMID- 17191214
TI  - Comparison of radial versus femoral approach for percutaneous coronary
      interventions in octogenarians.
AB  - BACKGROUND: The safety and efficacy of a radial approach for percutaneous
      coronary intervention (PCI) in octogenarians is not well established. METHODS: To
      evaluate the benefits of a radial approach for preventing vascular complications
      after PCI, clinical, procedural, and outcome data were prospectively collected
      and compared for 228 octogenarians undergoing elective PCI either through a
      radial or a femoral approach. RESULTS: Radial approach was associated with longer
      cannulation (3.1 +/- 2.9 vs. 2.0 +/- 2.0 min, P < 0.001) and fluoroscopy times
      (19.3 +/- 16.1 vs. 16.1 +/- 11.8 min, P = 0.04), greater utilization of contrast
      media (224 +/- 46 vs. 182 +/- 20 ml, P < 0.001) and higher crossover rate (11 vs
      4%, P = 0.03) to alternate access site compared with the femoral approach.
      However, ambulation time (5.2 +/- 3.1 vs. 11.6 +/- 6.3 hr, P < 0.001), access
      site bleeding (4 vs. 14%, P = 0.007), hematoma (1 vs. 11%, P = 0.001) or any
      vascular complication (5 vs 26%, P = 0.001) were significantly reduced with a
      radial approach. Procedural success rates were equivalent with both approaches.
      Multivariate regression analysis identified radial approach (OR = 0.23; CI =
      0.08, 0.65) as an independent negative predictor of postprocedural vascular
      complications. CONCLUSION: Radial approach for PCI in octogenarians is
      technically challenging for the operator and exposes patients to greater volume
      of nephrotoxic contrast media. However, it results in early ambulation and
      significantly reduces vascular complications in this high risk population. These
      findings support a strategy of preprocedural risk assessment and use of radial
      approach for PCI in a select group of octogenarians to maximize benefits offered
      by this technique.

PMID- 17191215
TI  - Provisionial SFA stenting.

PMID- 17191216
TI  - Novel cyclooxygenase-catalyzed bioactive prostaglandin F2alpha from physiology to
      new principles in inflammation.
AB  - Prostaglandin F2alpha (PGF2alpha), a foremost stable vasoactive cyclooxygenase
      (COX)-catalyzed prostaglandin, regulates a number of key physiological functions
      such as luteolysis, ovarian function, luteal maintenance of pregnancy, and
      parturition as a constitutive part of ongoing reproductive processes of the body.
      It has recently been implicated in the regulation of intricate pathophysiological
      processes, such as acute and chronic inflammation, cardiovascular and rheumatic
      diseases. Since the discovery of a second isoform of COXs, it has been shown that
      PGF2alpha can be formed in vivo from arachidonic acid through both isoforms of
      COXs, namely cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Being
      synthesized in various parts of the body, it metabolizes instantly to a number of
      rather inactive metabolites mainly in the lungs, liver, kidney, and efficiently
      excretes into the urine. 15-Keto-dihydro-PGF2alpha, a major stable metabolite of
      PGF2alpha that reflects in vivo PGF2alpha biosynthesis, is found in larger
      quantities than its parent compound in the circulation and urine in basal
      physiological conditions, with short-lived pulses during luteolysis, induced
      termination of pregnancy and parturition, and is increased in tissues and various
      body fluids during acute, sub-chronic, and severe chronic inflammation. Further,
      the close relationship of PGF2alpha with a number of risk factors for
      atherosclerosis indicates its major role in inflammation pathology. This review
      addresses multiple aspects of PGF2alpha in addition to its emerging role in
      physiology to inflammation.

PMID- 17191217
TI  - Lipoxygenase inhibitors: a comparative QSAR study review and evaluation of new
      QSARs.
AB  - This paper contains a quantitative structure activity relationship (QSAR) study
      for lipoxygenase (LO) inhibitors. It reveals that in almost all cases, the clog P
      parameter plays an important part in the QSARs (linear or bilinear model). In
      some cases the steric factors such as the overall molar refractivity (CMR) or the
      substituents molar refractivity (MR) (linear or parabola) are important.
      Electronic effects are comparatively unimportant. The study shows that log P as
      calculated from the Clog P program is suitable for this form of QSAR study.

PMID- 17191218
TI  - Stepladder artifact in coronary computed tomography angiography.

PMID- 17191219
TI  - Repeat right transradial percutaneous coronary intervention in a patient with
      dextrocardia: the right approach to the right-sided heart.
AB  - Dextrocardia (DC) is a rare cardiac condition in which the cardiac location, as
      well as apex, is rightwardly displaced. As the incidence of atherosclerotic
      disease is similar to that of the general population, there have been few reports
      of percutaneous coronary interventions (PCIs) in these patients. Proposed
      technical strategies for successful angiography and PCI in DC include counter
      directional torquing of the catheter, as well as right-left mirror-image
      inversion angiographic views. All previous reports of DC PCIs have been via
      transfemoral access.We present a case of successful repeat transradial PCI in a
      patient with DC. This is first report of transradial coronary angiography, PCI,
      or repeat PCI in a DC patient. A literature review of technical considerations,
      including our own recommendations for guide catheter selection, are discussed. We
      also review the anatomic variations and epidemiology of DC. Although access
      complications for transradial PCI is known to be lower than that of the
      transfemoral approach, challenges in technique and concern of repeat access have
      limited the popularity of the former. Our report demonstrates the safety and
      feasibility of transradial angiography, PCI, and even repeat PCI, in the rare
      patient with DC.

PMID- 17191220
TI  - Rescue left main coronary artery stenting for acute myocardial ischemia after
      coronary angiography in a 7-year-old girl with homozygous familial
      hypercholesterolemia.
AB  - Homozygous familial hypercholesterolemia (HFH), resulting from mutation of the
      low-density lipoprotein (LDL) receptor gene with subsequent defective catabolism
      of the LDL cholesterol, leads to premature atherosclerosis and coronary artery
      disease. We report a successful urgent stent implantation in a 7-year-old patient
      with HFH and a severe left main coronary artery stenosis, who presented critical
      acute myocardial ischemia immediately after left coronary angiography.
      Percutaneous transluminal coronary angiography with stent implantation allowed
      for rapid coronary flow reestablishment without sequelae. Aggressive lipid
      lowering therapy with high doses statins and LDL-apheresis was maintained,
      together with lifelong antiaggregant acetylsalicylic treatment with good short
      term patency of the stent at 1-year follow-up. In conclusion, coronary artery
      stent implantation may be considered as a valid rescue therapeutic alternative
      for pediatric patients with HFH and severe ostial coronary stenosis in case of
      emergency.

PMID- 17191223
TI  - Maternally imprinted microRNAs are differentially expressed during mouse and
      human lung development.
AB  - MicroRNAs (miRNAs) are a recently discovered class of noncoding genes that
      regulate the translation of target mRNA. More than 300 miRNAs have now been
      discovered in humans, although the function of most is still unknown. A highly
      sensitive, semiquantitative real-time polymerase chain reaction method was used
      to reveal the differential expression of several miRNAs during the development of
      both mouse and human lung. Of note was the up-regulation in neonatal mouse and
      fetal human lung of a maternally imprinted miRNA cluster located at human
      chromosome 14q32.31 (mouse chromosome 12F2), which includes the miR-154 and miR
      335 families and is situated within the Gtl2-Dio3 domain. Conversely, several
      miRNAs were up-regulated in adult compared with neonatal/fetal lung, including
      miR-29a and miR-29b. Differences in the spatial expression patterns of miR-154,
      miR-29a, and miR-26a was demonstrated using in situ hybridization of mouse
      neonatal and adult tissue using miRNA-specific locked nucleic acid (LNA) probes.
      Of interest, miR-154 appeared to be localized to the stroma of fetal but not
      adult lungs. The overall expression profile was similar for mouse and human
      tissue, suggesting evolutionary conservation of miRNA expression during lung
      development and demonstrating the importance of maternally imprinted miRNAs in
      the developmental process.

PMID- 17191224
TI  - Two-dimensional and three-dimensional time-lapse microscopic magnetic resonance
      imaging of Xenopus gastrulation movements using intrinsic tissue-specific
      contrast.
AB  - The amphibian embryo undergoes radical tissue transformations during blastula and
      gastrula stages, but live observation of internal morphogenetic events by optical
      microscopy is not feasible due to the opacity of the early embryo. Here, we
      report on the use of microscopic magnetic resonance imaging (MRI) to directly
      follow morphogenetic movements during blastula and gastrula stages of the Xenopus
      laevis embryo. We compare three different MRI modalities that take advantage of
      the intrinsic contrast present in embryonic tissues: three-dimensional (3D) fat
      imaging, 3D water-imaging, and 2D high-speed high-resolution imaging of early
      embryonic stages. We show that the features revealed by the intrinsic contrast
      correlate with the histological structure of the embryo. Using this tissue
      specific intrinsic contrast, the main embryonic tissues and internal tissue
      movements as well as archenteron invagination can be differentiated without cell
      labeling. We present 2D and 3D time-lapse sequences of early Xenopus embryonic
      development, spanning the stages from early blastula to the end of gastrula,
      which show the complex internal rearrangements of gastrulation in essentially
      real-time.

PMID- 17191225
TI  - Augmented generalized SENSE reconstruction to correct for rigid body motion.
AB  - The correction of motion artifacts continues to be a significant problem in MRI.
      In the case of uncooperative patients, such as children, or patients who are
      unable to remain stationary, the accurate determination and correction of motion
      artifacts becomes a very important prerequisite for achieving good image quality.
      The application of conventional motion-correction strategies often produces
      inconsistencies in k-space data. As a result, significant residual artifacts can
      persist. In this work a formalism is introduced for parallel imaging in the
      presence of motion. The proposed method can improve overall image quality because
      it diminishes k-space inconsistencies by exploiting the complementary image
      encoding capacity of individual receiver coils. Specifically, an augmented
      version of an iterative SENSE reconstruction is used as a means of synthesizing
      the missing data in k-space. Motion is determined from low-resolution navigator
      images that are coregistered by an automatic registration routine. Navigator data
      can be derived from self-navigating k-space trajectories or in combination with
      other navigation schemes that estimate patient motion. This correction method is
      demonstrated by interleaved spiral images collected from volunteers. Conventional
      spiral scans and scans corrected with proposed techniques are shown, and the
      results illustrate the capacity of this new correction approach.

PMID- 17191226
TI  - Efficient in vivo 31P magnetization transfer approach for noninvasively
      determining multiple kinetic parameters and metabolic fluxes of ATP metabolism in
      the human brain.
AB  - ATP metabolism is controlled mainly by ATP synthase (ATP(ase)) and creatine
      kinase (CK) reactions that regulate cerebral ATP production, transportation, and
      utilization. These coupled reactions constitute a chemical exchange metabolic
      network of PCr<-->ATP<-->Pi characterized by two forward and two reverse reaction
      fluxes, which can be studied noninvasively by in vivo (31)P MRS combined with
      magnetization transfer (MT). However, it is still debated whether current MT
      approaches can precisely determine all of these fluxes. We developed and tested a
      modified in vivo (31)P MT approach based on a multiple single-site saturation
      (MSS) technique to study the entire PCr<-->ATP<-->Pi network in human occipital
      lobe at 7T. Our results reveal that 1) the MSS MT approach can explicitly
      determine all four reaction fluxes with a minimal number of (31)P spectra; 2) the
      three-spin exchange model accurately determines reverse reaction fluxes,
      resulting in equal forward and reverse fluxes for both CK and ATP(ase) reactions;
      and 3) the ATP synthesis rate (8.8 +/- 1.9 micromol/g/min, N = 11) measured in
      the human brain reflects cerebral oxidative phosphorylation. The MSS MT approach
      should provide an important modality for noninvasively studying the essential
      roles of ATP metabolism in brain bioenergetics, function, and diseases.

PMID- 17191227
TI  - Quantitative BOLD: mapping of human cerebral deoxygenated blood volume and oxygen
      extraction fraction: default state.
AB  - Since Ogawa et al. (Proc Natl Acad Sci USA 1990;87:9868-9872) made the
      fundamental discovery of blood oxygenation level-dependent (BOLD) contrast in
      MRI, most efforts have been directed toward the study of dynamic BOLD (i.e.,
      temporal changes in the MRI signal during changes in brain activity). However,
      very little progress has been made in elucidating the nature of BOLD contrast
      during the resting or baseline state of the brain, which is important for
      understanding normal human performance because it accounts for most of the
      enormous energy budget of the brain. It is also crucial for deciphering the
      consequences of baseline-state impairment by cerebral vascular diseases. The
      objective of this study was to develop a BOLD MR-based method that allows
      quantitative evaluation of tissue hemodynamic parameters, such as the blood
      volume, deoxyhemoglobin concentration, and oxygen extraction fraction (OEF). The
      proposed method, which we have termed quantitative BOLD (qBOLD), is based on an
      MR signal model that incorporates prior knowledge about brain tissue composition
      and considers signals from gray matter (GM), white matter (WM), cerebrospinal
      fluid (CSF), and blood. A 2D gradient-echo sampling of spin-echo (GESSE) pulse
      sequence is used for the acquisition of the MRI signal. The method is applied to
      estimate the hemodynamic parameters of the normal human brain in the baseline
      state.

PMID- 17191228
TI  - Variance of estimated DTI-derived parameters via first-order perturbation
      methods.
AB  - In typical applications of diffusion tensor imaging (DTI), DT-derived quantities
      are used to make a diagnostic, therapeutic, or scientific determination. In such
      cases it is essential to characterize the variability of these tensor-derived
      quantities. Parametric and empirical methods have been proposed to estimate the
      variance of the estimated DT, and quantities derived from it. However, the former
      method cannot be generalized since a parametric distribution cannot be found for
      all DT-derived quantities. Although powerful empirical methods, such as the
      bootstrap, are available, they require oversampling of the diffusion-weighted
      imaging (DWI) data. Statistical perturbation methods represent a hybrid between
      parametric and empirical approaches, and can overcome the primary limitations of
      both methods. In this study we used a first-order perturbation method to obtain
      analytic expressions for the variance of DT-derived quantities, such as the
      trace, fractional anisotropy (FA), eigenvalues, and eigenvectors, for a given
      experimental design. We performed Monte Carlo (MC) simulations of DTI experiments
      to test and validate these formulae, and to determine their range of
      applicability for different experimental design parameters, including the signal
      to-noise ratio (SNR), diffusion gradient sampling scheme, and number of DWI
      acquisitions. This information should be useful for designing DTI studies and
      assessing the quality of inferences drawn from them.

PMID- 17191229
TI  - Automated estimation of tumor probability in prostate magnetic resonance
      spectroscopic imaging: pattern recognition vs quantification.
AB  - Despite its diagnostic value and technological availability, (1)H NMR
      spectroscopic imaging (MRSI) has not found its way into clinical routine yet.
      Prerequisite for the clinical application is an automated and reliable method for
      the diagnostic evaluation of MRS images. In the present paper, different
      approaches to the estimation of tumor probability from MRSI in the prostate are
      assessed. Two approaches to feature extraction are compared: quantification
      (VARPRO, AMARES, QUEST) and subspace methods on spectral patterns (principal
      components, independent components, nonnegative matrix factorization, partial
      least squares). Linear as well as nonlinear classifiers (support vector machines,
      Gaussian processes, random forests) are applied and discussed. Quantification
      based approaches are much more sensitive to the choice and parameterization of
      the quantification algorithm than to the choice of the classifier. Furthermore,
      linear methods based on magnitude spectra easily achieve equal performance and
      also allow for biochemical interpretation in combination with subspace methods.
      Nonlinear methods operating directly on magnitude spectra achieve the best
      results but are less transparent than the linear methods.

PMID- 17191230
TI  - Quantitative proton magnetic resonance spectroscopy of the human cervical spinal
      cord at 3 Tesla.
AB  - Cervical spinal cord spectroscopy has the potential to add metabolic information
      to spinal cord MRI and improve the clinical evaluation and research investigation
      of spinal cord diseases, such as multiple sclerosis (MS) and intraspinal tumors.
      However, in vivo proton MR spectroscopy ((1)H-MRS) of the spinal cord is
      difficult to perform due to magnetic field inhomogeneities, physiological
      movements, and the size of the anatomical region of interest (ROI). For these
      reasons, few spinal cord (1)H-MRS studies have been undertaken and two
      preliminary studies on a 3T system were only recently presented as abstracts. In
      this work we demonstrate the feasibility of cervical spinal cord quantitative
      (1)H-MRS on a clinical 3T system, propose a study protocol, and report
      quantification results obtained from healthy volunteers. The main metabolite
      concentration ratios obtained in 10 healthy subjects, as provided by LCModel,
      were as follows: total N-acetyl aspartate/creatine (tNAA/Cr) 1.4 +/- 0.3,
      choline/creatine (Cho/Cr) 0.5 +/- 0.1, and myoinositol/creatine (mI/Cr) 1.7 +/-
      0.2. A significant difference was found between spinal cord tNAA, Cr, Cho, and mI
      concentration ratios and brainstem concentrations previously acquired on the same
      system.

PMID- 17191231
TI  - Serial in vivo MR tracking of magnetically labeled neural spheres transplanted in
      chronic EAE mice.
AB  - Neural stem cell (NSC) transplantation has been shown to attenuate the severity
      of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis (MS). Central to the future success of NSC transplantation in MS is the
      ability of transplanted cells to migrate from the site of transplantation to
      relevant foci of disease. Using magnetically labeled mouse neurospheres and human
      embryonic stem cell (hESC)-derived neurospheres, we applied serial magnetic
      resonance imaging (MRI) to assess the biodynamics of transplanted cell migration
      in a chronic mouse EAE model. Magnetic labeling did not affect the in vitro and
      in vivo characteristics of cells as multipotential precursors. Cell migration
      occurred along white matter (WM) tracts (especially the corpus callosum (CC),
      fimbria, and internal capsule), predominantly early in the acute phase of
      disease, and in an asymmetric manner. The distance of cell migration correlated
      well with clinical severity of disease and the number of microglia in the WM
      tracts, supporting the notion that inflammatory signals promote transplanted cell
      migration. This study shows for the first time that hESC-derived neural
      precursors also respond to tissue signals in an MS model, similarly to rodent
      cells. The results are directly relevant for designing and optimizing cell
      therapies for MS, and achieving a better understanding of in vivo cell dynamics
      and cell-tissue interactions.

PMID- 17191232
TI  - Correlation of proton transverse relaxation rates (R2) with iron concentrations
      in postmortem brain tissue from alzheimer's disease patients.
AB  - Iron accumulates in the Alzheimer's disease (AD) brain and is directly associated
      with beta-amyloid pathology. The proton transverse relaxation rate (R(2)) has a
      strong linear relationship with iron concentrations in healthy brain tissue;
      however, an independent test of this relationship has not been extended to AD
      brain tissue. In this study in vitro single spin-echo (SE) measurements were made
      on tissue samples from four human AD brains using a 4.7T MRI research scanner.
      R(2) values were calculated for 14 cortical and subcortical gray matter (GM) and
      white matter (WM) regions. Atomic absorption spectroscopy was used to measure
      iron concentrations in the corresponding excised brain regions. Significant
      positive linear correlations were observed between R(2) values and iron
      concentrations in GM regions assessed across individual tissue samples and data
      averaged by brain region. With the use of a predictive model for R(2), a
      threshold iron concentration of 55 microg Fe/g wet tissue was determined above
      which R(2) appears to be dominated by the affects of iron in AD brain tissue.
      High-field MRI may therefore be a useful research tool for assessing brain iron
      changes associated with AD.

PMID- 17191233
TI  - Classification of spatiotemporal hemodynamics from brain perfusion MR images
      using expectation-maximization estimation with finite mixture of multivariate
      gaussian distributions.
AB  - The ability to cluster different perfusion compartments in the brain is critical
      for analyzing brain perfusion. This study presents a method based on a mixture of
      multivariate Gaussians (MoMG) and the expectation-maximization (EM) algorithm to
      dissect various perfusion compartments from dynamic susceptibility contrast (DSC)
      MR images so that each compartment comprises pixels of similar signal-time
      curves. This EM-based method provides an objective way to 1) delineate an area to
      serve as the in-plane arterial input function (AIF) of the feeding artery for
      adjacent tissues to better quantify the relative cerebral blood volume (rCBV),
      relative cerebral blood flow (rCBF), and mean transit time (MTT); 2) demarcate
      regions with abnormal perfusion derangement to facilitate diagnosis; and 3)
      obtain parametric maps with supplementary information, such as temporal scenarios
      and recirculation of contrast agent. Results from normal subjects show that
      perfusion cascade manifests (in order of appearance) the arteries, gray matter
      (GM), white matter (WM), veins and sinuses, and choroid plexus mixed with
      cerebrospinal fluid (CSF). The averaged rCBV, rCBF, and MTT ratios between GM and
      WM are in good agreement with those in the literature. Results from a patient
      with cerebral arteriovenous malformation (CAVM) showed distinct spatiotemporal
      characteristics between perfusion patterns, which allowed differentiation between
      pathological and nonpathological areas.

PMID- 17191234
TI  - Differential gene expression patterns in porcine nuclear transfer embryos
      reconstructed with fetal fibroblasts and mesenchymal stem cells.
AB  - The present study compared the developmental ability and gene expression pattern
      at 4-cell, 8-cell, morula, and blastocyst stages of porcine nuclear transfer (NT)
      embryos from fetal fibroblasts (FFs) and mesenchymal stem cells (MSCs), in vitro
      fertilized (IVF), and in vivo derived embryos. MSC-NT embryos showed enhanced
      blastocyst formation, higher total cell number, and a low incidence of apoptosis
      compared to FF-NT embryos. Alterations in the expression pattern of genes
      implicated in transcription and pluripotency (Oct4, Stat3, Nanog), DNA
      methylation (Dnmt1, Dnmt3a), histone deacetylation (Hdac2), growth factor
      signaling, and imprinting (Igf2, Igf2r) and apoptosis (Bax, Bcl2) regulation were
      observed in NT embryos. The expression of transcripts in MSC-NT embryos more
      closely followed that of the in vivo derived embryos compared with FF-NT embryos.
      In conclusion, MSCs with a relatively undifferentiated genome might serve as
      suitable donors that could be more efficiently reprogrammed to re-activate
      expression of early embryonic genes in porcine NT.

PMID- 17191235
TI  - A new quantitative analysis system for the evaluation of coronary bifurcation
      lesions: comparison with current conventional methods.
AB  - BACKGROUND: Objective conventional quantitative angiographic systems are designed
      to automatically follow the contours of straight vascular segments and not of
      bifurcations. Recently a new analysis method was specifically developed for
      bifurcation lesions, able to automatically divide the lesion into three separate
      segments. In this study, we aimed to assess whether the smaller interaction
      required by the analyst could reduce the analysis time and inter and intra
      observer variability when compared with a conventional analysis. METHOD: We used
      a dedicated system (QVA-CMS V. 6.0 with the Bifurcation Module, MEDIS, Leiden,
      The Netherlands) applying a minimum cost algorithm tuned to detect the contours
      of the proximal main vessel (PMV), distal main vessel (DMV), and side-branch
      (SB). We assessed the intra- and the interobserver agreement in measurements of
      minimal lumen diameter (MLD) and percentage diameter stenosis (%DS) of the PMV
      and DMV, as well as of the SB ostium in 30 angiograms of patients before and
      after percutaneous coronary angioplasty with stenting of both branches. The
      consensus between measurements by two observers and by the same observer was
      analyzed using the intra- and interclass correlation coefficient and the
      reliability coefficients for all measurements. Bland-Altman plots before and
      after PCI were also generated to assess the relationship between variability and
      absolute measurements. RESULTS: Before PCI, intra- and interobserver
      variabilities were consistently lower for the new QVA system, with a significant
      difference for lesion length in the SB. Post-PCI data showed a greater
      variability in the assessment of diameter stenosis with both techniques. The time
      for analysis was significantly lower both before and after PCI for QVA compared
      with quantitative coronary angiography (QCA) (4.7 +/- 1.1 min versus 6.2 +/- 1.3
      min, P < 0.0001). CONCLUSION: Our results demonstrate that this new quantitative
      bifurcation analysis system can be consistently applied to the analysis of
      bifurcation lesions before and after angioplasty, with an intra- and
      interobserver reproducibility equal to or better than the conventional analysis
      system with a significantly shorter analysis time.

PMID- 17191236
TI  - Spontaneous migration of an inferior vena cava filter resulting in cardiac
      tamponade and percutaneous filter retrieval.
AB  - Thromboembolic disease accounts for thousands of hospitalizations every year in
      the US. Its primary management consists of anticoagulation. However, in certain
      instances this may be contraindicated or not sufficient. Mechanic occlusion of
      the inferior vena cava (IVC) becomes then a viable alternative. In this case a 35
      year-old man presented with a saddle pulmonary embolus but was unable to be
      anticoagulated due to intestinal bleed. A removable IVC filter was then placed.
      The filter spontaneously migrated into the right atrium causing severe tricuspid
      regurgitation, perforation of the atrial wall, and cardiac tamponade. The device
      was successfully retrieved percutaneously and the patient discharged from the
      hospital in stable condition. This case illustrates the potentially lethal
      complications associated with the use of IVC filters, as well as the possibility
      to percutaneously recover them from within the right atrium.

PMID- 17191237
TI  - Coarctation of the aorta: stenting in children and adults.
AB  - Coarctation of the aorta may present in infants, children, or adults, and it
      requires treatment to prevent serious morbidity and mortality. Recent advances in
      equipment and a growing collective experience have made placement of balloon
      expandable stents a safe and effective alternative to surgery or angioplasty in a
      growing range of patients. This review seeks to provide a working aid for
      stenting of coarctation of the aorta, based on the techniques and technical
      considerations in practice at our institution. Between 1989 and 2005, the
      Congenital Cardiovascular Interventional Study Consortium (CCISC), a consortium
      of 17 centers, of which our institution is the largest contributor, performed 588
      stent placements for coarctation of the aorta. Of the 588 procedures, 580 (98.6%)
      were successful, as defined by reduction of the gradient to less than 20 mm Hg or
      increase of the ratio of the diameter of the coarctation area (CoA) to the
      diameter of the descending aorta (DAo) to at least 0.8. There were a total of 84
      complications occurring in 69/588 (11.7%) cases. The most common significant
      complications were femoral access vessel related 15/588 (2.6%), aneurysm
      formation 13/588 (2.2%), aortic dissection 9/588 (1.5%), and cerebrovascular
      accident 6/588 (1.0%). There were two procedure-related deaths (0.3%) recorded in
      the 16-year period. Many of these significant complications occurred in the same
      patients. Balloon-expandable stents should be considered a safe and very
      effective treatment modality in a significant subset of patients with coarctation
      of the aorta.

PMID- 17191238
TI  - Predictors of restenosis after treatment of bifurcational lesions with paclitaxel
      eluting stents: a multicenter prospective registry of 150 consecutive patients.
AB  - OBJECTIVES: The aim of the study was the assessment of the clinical, angiographic
      and procedural characteristics correlated with freedom from adverse events at 1
      year in a real life setting of consecutive bifurcation lesions. BACKGROUND: Even
      if stent implantation has shown to be superior to conventional balloon
      angioplasty in most coronary lesions, bifurcation treatment with stent
      implantation both in main and in side branch (SB) still raises controversy.
      METHODS: We reviewed the results obtained in a prospective multicenter registry
      of 150 patients with 158 bifurcation lesions involving a SB of sufficient
      diameter to be treated, if necessary, with a polymer based paclitaxel eluting
      stent (PES, TAXUS). Two stents were used in 118 lesions (74.7%). Final kissing
      balloon inflation was performed in 87/118 lesions (73.7%) and in 30/40 lesions
      (75.0%) of the 2 and 1 stent group respectively. RESULTS: At 1-year clinical
      follow-up we observed 4 stent thromboses, all involving the SBs of the 2 stents
      group (2.7%). Unlike previous reports, revascularization involved the main vessel
      in the majority of patients (21/150, 14.0%). After an exploratory multivariable
      analysis the only parameter predictive of target lesion revascularization (TLR)
      (HR 0.52; CI 95% 0.11-0.86; p = 0.02) and target vessel revascularization (TVR)
      (HR 0.47; CI 95% 0.14-0.90; p = 0.03) was postprocedural main branch minimal
      lumen diameter (MB-MLD). CONCLUSIONS: In a real life setting of consecutive
      bifurcation lesions, thrombosis rate, concentrated in the SB and the 2-stents
      group, and need for target lesion revascularization remain higher than in less
      complex lesion subgroups treated with PES. No differences in immediate success
      and TLR were observed between 2 stents and 1 stent groups. The frequently
      observed suboptimal stent expansion and final MB-MLD predict 1 year
      revascularization.

PMID- 17191239
TI  - Interatrial septum rupture during balloon measurement of a patent foramen ovale
      in a young patient presenting cryptogenic stroke.
AB  - We report the case of a 36-year-old woman admitted for cryptogenic stroke, in
      whom the Patent Foramen Ovale (PFO) diameter measurement, with a purpose built
      sizing balloon, performed before the closure procedure, was complicated with the
      rupture of the inter-atrial septum generating an Atrial Septal Defect (ASD) with
      a significant left-to-right shunt. This kind of complication may not be easy to
      handle, changing the initial procedural strategy from PFO to ASD closure
      technique requiring specific material and operator's technical skill.

PMID- 17191240
TI  - Relocation of minimal luminal diameter after bare metal and drug-eluting stent
      implantation: incidence and impact on angiographic late loss.
AB  - Late loss (LL) has been a fundamental angiographic end-point in drug-eluting
      stents (DES) clinical trials. However, calculation of LL may be affected by a
      mismatch between post-procedure (PO) and follow-up (FU) sites of the minimal
      lumen diameter (MLD). Our aims were to investigate the incidence and
      methodological implications of the relocation of MLD after bare metal (BMS),
      sirolimus-eluting (SES), and paclitaxel-eluting (PES) stent implantation. Data
      from DIABETES I and II trials, which involved diabetic patients treated with BMS,
      SES, and PES, were analyzed. Angiographic data with matched projections between
      PO and 9-month angiographic FU were included. In-stent, in-lesion, and in-segment
      analyses included conventional and customized sub-segmental (5-mm/subsegment)
      methodology. MLD relocation was considered when the sites of MLD shifted a
      distance >> the intrinsic variability of the method. Conventional LL, site
      matched LL, maximal LL (MaxLL), and average LL (AvgLL) were calculated.
      Relationships between various LL and 1-year target lesion revascularization (TLR)
      were investigated. Post MLD was located distally, outside the stent, in > or =65%
      of the analyses. At FU, MLD relocation occurred in 70.5% (BMS), 40% (SES), and
      35% (PES). MLD shifted > or =11 mm on average, mainly towards the stented
      segment. MLD relocation still occurred in 42.8% (BMS), 33.7% (SES), and 36.4%
      (PES), when analysis was restricted to in-stent segment. Among LL measurements,
      MaxLL showed the best association with TLR rates. Relocation of the MLD is a
      frequent phenomenon after both BMS and DES, and should be taken into account when
      calculating LL. Comprehensive LL analyses, including MaxLL and AvgLL, provides a
      better appraisal of the biological and clinical effectiveness of DES.

PMID- 17191241
TI  - Detection and quantification of embolic particles during percutaneous coronary
      intervention to stable plaque: it correlates to coronary flow dynamics and
      myocardial damage.
AB  - OBJECTIVES: We detected embolic particles liberated from plaque during
      percutaneous coronary intervention (PCI) as high-intensity transient signals
      (HITS) with a Doppler guidewire and studied their impact on coronary flow
      dynamics and the myocardium in patients with stable angina pectoris. BACKGROUND:
      These embolic particles during PCI may cause myocardial injury. However, this was
      difficult to confirm because it was impossible to detect embolic particles.
      METHODS: We performed balloon angioplasty followed by stenting in 31 patients
      while monitoring coronary flow velocity. After PCI, we measured average peak
      velocity at baseline and after infusion of adenosine 5'-triphosphate to calculate
      coronary flow velocity reserve (CFVR) and coronary resistance index (CRI). In
      patients with PCI to the left coronary artery (n = 21), we calculated relative
      CFVR as the ratio of CFVR in the target vessel to that in the reference vessel.
      We measured cardiac troponin T (cTnT) the day after PCI. RESULTS: HITS were
      detected in 27 (87%) of 31 patients and the majority were observed after
      stenting. The total number of HITS was correlated with CRI (r = 0.36, P = 0.049)
      or relative CFVR (r = 0.65, P = 0.0036) but not with CFVR (r = 0.048, P = 0.82).
      Thirteen patients showed elevated cTnT (range, 0.05-0.31 ng/ml) and the total
      number of HITS was greater in those with elevated cTnT than in those without
      elevated cTnT (24 +/- 9 vs. 10 +/- 7, P = 0.0007). CONCLUSIONS: Embolic particles
      are frequently observed during PCI to stable plaque and the majority are
      liberated after stenting. There appears to be a quantitative relationship between
      amounts of HITS and coronary microvessel dysfunction and minor myocardial injury.

PMID- 17191242
TI  - Actual flip-angle imaging in the pulsed steady state: a method for rapid three
      dimensional mapping of the transmitted radiofrequency field.
AB  - A new method has been developed for fast image-based measurements of the
      transmitted radiofrequency (RF) field. The method employs an actual flip-angle
      imaging (AFI) pulse sequence that consists of two identical RF pulses followed by
      two delays of different duration (TR(1) < TR(2)). After each pulse, a gradient
      echo (GRE) signal is acquired. It has been shown theoretically and experimentally
      that if delays TR(1) and TR(2) are sufficiently short and the transverse
      magnetization is completely spoiled, the ratio r = S(2)/S(1) of signal
      intensities S(1) and S(2), acquired at the beginning of the time intervals TR(1)
      and TR(2), depends on the flip angle (FA) of applied pulses as r = (1 + n *
      cos(FA))/(n + cos(FA)), where n = TR(2)/TR(1). The method allows fast 3D
      implementation and provides accurate B(1) measurements that are highly
      insensitive to T(1). The unique feature of the AFI method is that it uses a
      pulsed steady-state signal acquisition. This overcomes the limitation of previous
      methods that required long relaxation delays between sequence repetitions. The
      method has been shown to be useful for time-efficient whole-body B(1) mapping and
      correction of T(1) maps obtained using a variable FA technique in the presence of
      nonuniform RF excitation.

PMID- 17191243
TI  - Serial triple quantum sodium MRI during non-human primate focal brain ischemia.
AB  - Triple quantum (TQ) sodium MRI techniques with clinically acceptable 18-min data
      acquisition times were demonstrated in vivo in a nonhuman primate model of focal
      brain ischemia. Focal brain ischemia was induced in four animals using
      embolization coils to occlude the posterior cerebral artery, and a balloon
      catheter to occlude the middle cerebral artery. A statistically significant
      increase (P < 0.001) in the TQ sodium MRI signal intensity in the ischemic
      hemisphere relative to the contralateral hemisphere was seen at all time points
      in all four animals. This increased TQ sodium MRI signal intensity was
      demonstrated as early as 0.6 hr after the onset of ischemia. The TQ sodium MRI
      hyperintensity corresponded to the anatomical location of the ischemic cortex, as
      indicated by the registration of the TQ imaging data with anatomical proton MRI
      data. The results demonstrate that early after the onset of ischemia, there was
      an increase in the TQ signal intensity in the ischemic hemisphere, and a
      negligible change in the single quantum (SQ) signal intensity.

PMID- 17191244
TI  - Artifact reduction in moving-table acquisitions using parallel imaging and
      multiple averages.
AB  - Two-dimensional (2D) axial continuously-moving-table imaging has to deal with
      artifacts due to gradient nonlinearity and breathing motion, and has to provide
      the highest scan efficiency. Parallel imaging techniques (e.g., generalized
      autocalibrating partially parallel acquisition GRAPPA)) are used to reduce such
      artifacts and avoid ghosting artifacts. The latter occur in T(2)-weighted multi
      spin-echo (SE) acquisitions that omit an additional excitation prior to imaging
      scans for presaturation purposes. Multiple images are reconstructed from
      subdivisions of a fully sampled k-space data set, each of which is acquired in a
      single SE train. These images are then averaged. GRAPPA coil weights are
      estimated without additional measurements. Compared to conventional image
      reconstruction, inconsistencies between different subsets of k-space induce less
      artifacts when each k-space part is reconstructed separately and the multiple
      images are averaged afterwards. These inconsistencies may lead to inaccurate
      GRAPPA coil weights using the proposed intrinsic GRAPPA calibration. It is shown
      that aliasing artifacts in single images are canceled out after averaging.
      Phantom and in vivo studies demonstrate the benefit of the proposed
      reconstruction scheme for free-breathing axial continuously-moving-table imaging
      using fast multi-SE sequences.

PMID- 17191245
TI  - Compensation for spin-lock artifacts using an off-resonance rotary echo in
      T1rhooff-weighted imaging.
AB  - The origin of image artifacts in an off-resonance spin-locking experiment is
      shown to be imperfections in the excitation flip angle. A pulse sequence for off
      resonance spin locking is implemented that compensates for imperfections in the
      excitation flip angle through an off-resonance rotary echo. The off-resonance
      rotary echo alternates the frequency offset and phase of the RF transmitter
      during two spin-locking pulses of equal duration. The underlying theory is
      detailed, and MR images demonstrate the effectiveness of the technique in agarose
      gel phantoms and in in vivo human brain at 3T.

PMID- 17191247
TI  - Systematic investigation of balanced steady-state free precession for functional
      MRI in the human visual cortex at 3 Tesla.
AB  - Previous studies have applied balanced steady-state free precession (bSSFP) to
      functional brain imaging. Methods that exploit the strong frequency dependence of
      the MR signal in the bSSFP transition band are strongly affected by field
      inhomogeneity and frequency drifts. Recent bSSFP studies using "on-resonance" (in
      the bSSFP passband) acquisition claimed that higher sensitivity was achieved
      compared to traditional fMRI methods. However, the contrast mechanism that
      generates activation-related signal changes in bSSFP imaging is not yet fully
      understood. We performed a systematic study of on-resonance bSSFP signal behavior
      using a multiecho balanced SSFP sequence with different TRs at 3 Tesla. We
      conclude that intravoxel dephasing, or the off-resonance averaged steady state,
      dominates the bSSFP signal decay and determines the bSSFP fMRI contrast.
      Experimental findings were confirmed by simulations based on existing theories
      for signal formation around blood vessels in inhomogeneous tissues. The
      activation-induced signal change in on-resonance bSSFP increases with TE, and the
      TE dependence of the contrast-to-noise ratio (CNR) in bSSFP is similar to that in
      gradient echo-planar imaging (GE-EPI). However, GE-EPI has a significantly higher
      CNR efficiency.

PMID- 17191248
TI  - 3D radial projection technique with ultrashort echo times for sodium MRI:
      clinical applications in human brain and skeletal muscle.
AB  - (23)Na MRI has the potential to noninvasively detect sodium (Na) content changes
      in vivo. The goal of this study was to implement (23)Na MRI in a clinical setting
      for neurooncological and muscular imaging. Due to the biexponential T(2) decay of
      the tissue Na signal with a short component, which ranges between 0.5-8 ms, the
      measurement of total Na content requires imaging techniques with echo times (TEs)
      below 0.5 ms. A 3D radial pulse sequence with a TE of 0.2 ms at a spatial
      resolution of 4 x 4 x 4 mm(3) was developed that allows the acquisition and
      presentation of Na images on the scanner. This sequence was evaluated in patients
      with low- and high-grade gliomas, and higher (23)Na MR signals corresponding to
      an increased Na content were found in the tumor regions. The contrast-to-noise
      ratio (CNR) between tumor and white matter increased from 0.8 +/- 0.2 to 1.3 +/-
      0.3 with tumor grade. In patients with an identified muscular (23)Na
      channelopathy (Paramyotonia congenita (PC)), induced muscle weakness led to a
      signal increase of approximately 18% in the (23)Na MR images, which was
      attributed to intracellular Na(+) accumulation in this region.

PMID- 17191249
TI  - Fast 3D 1H spectroscopic imaging at 3 Tesla using spectroscopic missing-pulse
      SSFP with 3D spatial preselection.
AB  - Three-dimensional (3D) (1)H MR spectroscopic imaging (SI) allows metabolic
      changes in human tissue to be identified. In clinical practice, fast acquisition
      techniques are required to achieve an adequate spatial resolution within
      acceptable total measurement times. In this study a novel fast pulse sequence for
      3D (1)H SI based on the condition of steady-state free precession (SSFP), termed
      "spectroscopic missing-pulse SSFP" (spMP-SSFP), is proposed. It combines 3D
      spatial preselection with the acquisition of full spin echoes (SEs), and thus
      makes subsequent phase correction of spectra redundant. The sequence was applied
      to a phantom and healthy human brains in vivo at 3 Tesla. Metabolic images are
      acquired with a spatial resolution of 1.8 cm(3) within a total measurement time
      of about 6 min. With a lower signal-to-noise ratio (SNR) per unit measurement
      time compared to previous spectroscopic SSFP implementations, 3D spatial
      preselection can now be realized with spMP-SSFP. Since the method does not
      require separate techniques for water and lipid suppression, and employs a simple
      data-processing approach, spMP-SSFP is a robust, fast SI method that requires
      only minimal user interaction.

PMID- 17191251
TI  - Microparticles and nanoparticles for drug delivery.
AB  - Particulate drug delivery systems have become important in experimental
      pharmaceutics and clinical medicine. The distinction is often made between micro-
      and nanoparticles, being particles with dimensions best described in micrometers
      and nanometers respectively. That size difference entails real differences at
      many levels, from formulation to in vivo usage. Here I will discuss those
      differences and provide examples of applications, for local and systemic drug
      delivery. I will outline a number of challenges of interest in particulate drug
      delivery.

PMID- 17191252
TI  - Botryllus schlosseri: a model ascidian for the study of asexual reproduction.
AB  - Botryllus schlosseri, a cosmopolitan colonial ascidian reared in the laboratory
      for more than 50 years, reproduces both sexually and asexually and is used as a
      model organism for studying a variety of biological problems. Colonies are formed
      of numerous, genetically identical individuals (zooids) and undergo cyclical
      generation changes in which the adult zooids die and are replaced by their
      maturing buds. Because the progression of the colonial life cycle is intimately
      correlated with blastogenesis, a shared staging method of bud development is
      required to compare data coming from different laboratories. With the present
      review, we aim (1) to introduce B. schlosseri as a valuable chordate model to
      study various biological problems and, especially, sexual and asexual
      development; (2) to offer a detailed description of bud development up to
      adulthood and the attainment of sexual maturity; (3) to re-examine Sabbadin's
      (1955) staging method and re-propose it as a simple tool for in vivo recognition
      of the main morphogenetic events and recurrent changes in the blastogenetic
      cycle, as it refers to the developmental stages of buds and adults.

PMID- 17191253
TI  - Temporomandibular joint formation and condyle growth require Indian hedgehog
      signaling.
AB  - The temporomandibular joint (TMJ) is essential for jaw function, but the
      mechanisms regulating its development remain poorly understood. Because Indian
      hedgehog (Ihh) regulates trunk and limb skeletogenesis, we studied its possible
      roles in TMJ development. In wild-type mouse embryos, Ihh expression was already
      strong in condylar cartilage by embryonic day (E) 15.5, and expression of Ihh
      receptors and effector genes (Gli1, Gli2, Gli3, and PTHrP) indicated that Ihh
      range of action normally reached apical condylar tissue layers, including
      polymorphic chondroprogenitor layer and articular disc primordia. In Ihh(-/-)
      embryos, TMJ development was severely compromised. Condylar cartilage growth,
      polymorphic cell proliferation, and PTHrP expression were all inhibited, and
      growth plate organization and chondrocyte gene expression patterns were abnormal.
      These severe defects were partially corrected in double Ihh(-/-)/Gli3(-/-)
      mutants, signifying that Ihh action is normally modulated and delimited by Gli3
      and Gli3(R) in particular. Both single and double mutants, however, failed to
      form an articular disc primordium, normally appreciable as an independent
      condensation between condylar apex and neighboring developing temporal bone in
      wild-type. This failure persisted at later stages, leading to complete absence of
      a normal functional disc and lubricin-expressing joint cavities. In summary, Ihh
      is very important for TMJ development, where it appears to regulate growth and
      elongation events, condylar cartilage phenotype, and chondroprogenitor cell
      function. Absence of articular disc and joint cavities in single and double
      mutants points to irreplaceable Ihh roles in formation of those critical TMJ
      components.

PMID- 17191254
TI  - Cloning and characterization of scale beta-keratins in the differentiating
      epidermis of geckoes show they are glycine-proline-serine-rich proteins with a
      central motif homologous to avian beta-keratins.
AB  - The beta-keratins constitute the hard epidermis and adhesive setae of gecko
      lizards. Nucleotide and amino acid sequences of beta-keratins in epidermis of
      gecko lizards were cloned from mRNAs. Specific oligonucleotides were used to
      amplify by 3'- and 5'-rapid amplification of cDNA ends analyses five specific
      gecko beta-keratin cDNA sequences. The cDNA coding sequences encoded putative
      glycine-proline-serine-rich proteins of 16.8-18 kDa containing 169-191 amino
      acids, especially 17.8-23% glycine, 8.4-14.8% proline, 14.2-18.1% serine. Glycine
      rich repeats are localized toward the initial and end regions of the protein,
      while a central region, rich in proline, has a strand conformation (beta-pleated
      fold) likely responsible for the formation of beta-keratin filaments. It shows
      high homology with a core region of other lizard keratins, avian scale, and
      feather keratins. Northern blotting and reverse transcriptase-polymerase chain
      reaction (RT-PCR) analysis show a higher beta-keratin gene expression in
      regenerating epidermis compared with normal epidermis. In situ hybridization
      confirms that mRNAs for these proteins are expressed in cells of the
      differentiating oberhautchen cells and beta-cells. Expression in adhesive setae
      of climbing lamellae was shown by RT-PCR. Southern blotting analysis revealed
      that the proteins are encoded by a multigene family. PCR analysis showed that the
      genes are presumably located in tandem along the DNA and are transcribed from the
      same DNA strand like in avian beta-keratins.

PMID- 17191256
TI  - Parental decisions to abort or continue a pregnancy following prenatal diagnosis
      of chromosomal abnormalities in a setting where termination of pregnancy is not
      legally available.
AB  - OBJECTIVE: To learn about parental decisions to abort or continue a pregnancy
      after prenatal diagnosis of chromosomal abnormalities among the population in
      Uruguay. METHODS: Between 1982 and 2003, 14 656 amniocentesis and 2740 chorionic
      villus samplings were performed in a referral Genetic Unit. Chromosomal anomalies
      were found in 376 cases (2.16%) and included Down syndrome, aneuploidies in which
      a severe prognosis was expected, sex chromosome aneuploidy and aneuploidies with
      a low risk of an abnormal clinical phenotype. The couples that received abnormal
      results were contacted by phone and asked if they had continued or interrupted
      the pregnancy after the diagnosis and genetic counseling. RESULTS: We contacted
      207 couples (55%). When confronted with Down syndrome or an aneuploidy in which a
      severe prognosis was expected, 89% and 96% of patients, respectively, decided to
      terminate the pregnancy. When confronted with sex chromosome aneuploidy or
      aneuploidies with a low risk of an abnormal clinical phenotype, 79% and 90% of
      patients, respectively, decided to continue the pregnancy. CONCLUSIONS: The
      present study shows that when faced with an anomaly such as Down syndrome and
      aneuploidies in which a severe prognosis was expected, most of the couples
      decided to terminate the pregnancy, although TOP is not legally available in
      Uruguay.

PMID- 17191255
TI  - Type I interferon response against viral and non-viral gene transfer in human
      tumor and primary cell lines.
AB  - BACKGROUND: Type I interferon (IFN-alpha/beta) response is one of the major host
      defence mechanisms against viruses. Some recent reports suggest that IFNs may
      interfere with the efficacy of both non-viral and virus-vector-mediated
      therapeutic gene transfer. METHODS: The type I IFN response upon different gene
      transfer methods in human tumor and primary cell lines was studied by analysing
      IFN-beta mRNA expression, secretion of type I IFNs and accumulation of IFN
      alpha/beta-induced MxA protein (myxovirus resistance protein A). RESULTS:
      Infection with avirulent Semliki Forest virus A7[74] induced MxA protein
      accumulation and increased the IFN-beta mRNA level, whereas none of the studied
      virus vectors (adenovirus, CRAd, lentivirus or AAV) induced IFN response.
      However, plasmid DNA induced the accumulation of MxA protein when transfected
      with several commercial transfection reagents. RNA transfection appeared to be an
      efficient inducer of type I IFN response: replicating alphaviral RNA, eukaryotic
      total RNA, or mRNA all induced both MxA protein accumulation and IFN-beta
      expression. siRNA transfection failed to induce MxA response. CONCLUSIONS: The
      non-viral gene transfer methods have gained more interest in recent years due to
      their better safety profiles when compared to their viral counterparts. However,
      the efficiency of non-viral gene transfer is well below those reached by viral
      vector systems. The type I interferon response induced by non-viral methods may
      in part contribute to this inefficiency, while most currently used viral gene
      transfer vectors fail to induce or are able to suppress type I IFN response.

PMID- 17191258
TI  - Impact of decision-making in a multidisciplinary perinatal team.
AB  - OBJECTIVES: (1) To describe the characteristics of decision-making about
      management of unborn infants with serious anomalies by a multidisciplinary
      perinatal team. (2) To evaluate the impact of multidisciplinary team discussions
      on the degree to which decisions about the management of unborn infants with
      serious anomalies are supported. (3) To evaluate the impact of the team
      discussions on the arguments used by physicians for their preferences concerning
      management. METHODS: Prospective analysis of 78 cases discussed within the
      multidisciplinary perinatal team of a tertiary centre by means of an anonymous
      one-page questionnaire with structured questions pertaining to the opinion of the
      responder on medical management of each case. RESULTS: We did not find systematic
      differences between specialties prior to the discussion of cases. However,
      discussion with the multidisciplinary perinatal team improved decision-making
      about management of unborn infants with serious anomalies by enhancing the degree
      of support for the decisions taken. The discussions of the team did not change
      the physicians' arguments mentioned for their preferences. CONCLUSION:
      Multidisciplinary team discussions improve decision-making about management of
      unborn infants with serious congenital anomalies.

PMID- 17191257
TI  - Free fetal DNA is not increased before 20 weeks in intrauterine growth
      restriction or pre-eclampsia.
AB  - BACKGROUND: The aim of this study was to quantify maternal plasma fetal DNA and
      total DNA in early pregnancy in intrauterine growth restriction (IUGR) or pre
      eclampsia (PET). METHODS: A nested case control study was carried out in a
      University Teaching Hospital. Plasma samples were obtained from 1993 women before
      20 weeks of gestation. Pregnancies complicated by IUGR or PET were identified and
      compared to controls. DNA was extracted and real-time quantitative PCR applied
      for the SRY and beta-actin genes. IUGR or PET groups were compared to controls
      using the chi(2) and Wilcoxon rank sum tests. RESULTS: SRY was detected in 86% of
      IUGR (31/36), 94% of PET (15/16) and 78% of controls (56/72). The median SRY was
      similar in women with IUGR (28 GE/mL) or PET (30.5 GE/mL) and controls (27.5
      GE/mL). beta-actin was increased in the IUGR group (3975 GE/mL) compared to
      controls (1835 GE/mL) (p = 0.045). Cigarette consumption was greater in the IUGR
      group compared to controls (p = 0.004). CONCLUSIONS: Fetal DNA quantitation in
      maternal plasma before 20 weeks is not a useful predictor of IUGR or PET. beta
      actin levels were elevated before 20 weeks in women with IUGR and may be a marker
      of maternal susceptibility to this condition.

PMID- 17191259
TI  - Prenatal diagnosis for a novel homozygous mutation in PKLR gene in an Indian
      family.
AB  - OBJECTIVE: To provide prenatal diagnosis of pyruvate kinase deficiency by direct
      DNA analysis in an Indian family. MATERIALS AND METHOD: This case report
      describes diagnosis of a novel homozygous mutation in PKLR gene that subsequently
      helped the family in the next pregnancy. RESULTS: Advancement in molecular
      genetics has resulted in the prenatal diagnosis of relatively uncommon genetic
      disorders like pyruvate kinase deficiency. CONCLUSION: This case reiterates the
      importance of application of molecular genetics in clinical practice and prenatal
      diagnosis especially for rare, incurable genetic disorders.

PMID- 17191260
TI  - Detection of fetomaternal hemorrhage following chorionic villus sampling by
      Kleihauer Betke test and rise in maternal serum alpha feto protein.
AB  - OBJECTIVES: To assess incidence and volume of fetomaternal hemorrhage (FMH) after
      chorionic villus sampling (CVS) by Kleihauer Betke test (KBT) and rise in
      maternal protein (MSAFP). METHODS: A prospective study was conducted on 61 cases
      requiring CVS. FMH due to CVS was assessed by KBT and MSAFP. RESULTS: Out of 61
      cases, 60 (98.36%) cases showed FMH by MSAFP while all showed FMH by KBT. Median
      volume of FMH detected by MSAFP was 0.06 mL (25 to 75th interquartile (IQR) 0.01
      to 0.12 mL) and by KBT was 0.45 mL (25 to 75th IQR 0.09 to 0.90). Mean volume of
      FMH detected by MSAFP was 0.1 + 0.1424 mL and by KBT was 0.58 + 0.637 mL.
      Significant FMH up to 0.1 mL was found in 20 (32.8%) and 45 (60.6%) by MSAFP and
      KBT respectively. CONCLUSION: MSAFP and KBT are sensitive to detect FMH. KBT
      estimates more FMH than MSAFP. Fifty micrograms of anti-D is sufficient to cover
      FMH during CVS.

PMID- 17191261
TI  - Pregnancy and postnatal outcome of mosaic isochromosome 20q.
AB  - Prenatally diagnosed mosaicism for isochromosome 20q is generally reported in
      association with a normal outcome at birth and is rarely confirmed postnatally.
      However, the origin of these abnormal cells is unclear and there are few reports
      of long-term outcomes. We present an additional case of prenatally detected
      isochromosome 20q, with normal outcome up to age 3.6 years. The abnormal cells,
      while present at high levels in the amniotic fluid, could not be confirmed in
      placenta or fetal blood. Nonetheless, based on a review of the literature, the
      level of isochromosome 20q cells found is associated with risk of abnormal
      outcome, suggesting a possible effect in some cases.

PMID- 17191262
TI  - Two- or three-dimensional ultrasonography to predict pulmonary hypoplasia in
      pregnancies complicated by preterm premature rupture of the membranes.
AB  - OBJECTIVES: The purpose of this study was to compare 3D lung volume measurements
      with 2D biometric parameters in predicting pulmonary hypoplasia in pregnancies
      complicated by preterm premature rupture of the membranes (PPROM). METHODS: In
      this prospective study, 18 pregnancies complicated by PPROMs at a mean 21 weeks'
      gestation (range 14-32 weeks) were examined. The 3D lung volume measurements and
      the following 2D biometric parameters were measured: thoracic circumference (TC)
      versus gestational age or femur length (FL), the TC/abdominal circumference (AC)
      ratio and the thoracic area/heart area (TA/HA) ratio. The sensitivity,
      specificity, positive and negative predictive value of each measurement to
      diagnose pulmonary hypoplasia were compared. Pulmonary hypoplasia was diagnosed
      on the basis of clinical, radiological and/or pathologic criteria. RESULTS: The
      incidence of pulmonary hypoplasia was 33.3%. The best diagnostic accuracy for
      predicting pulmonary hypoplasia was achieved using the 3D lung volume
      measurements versus gestational age (sensitivity 83%, specificity 100%, positive
      predictive value 100% and negative predictive value 92%). CONCLUSIONS: Three
      dimensional lung volume measurements seem to be promising in predicting pulmonary
      hypoplasia prenatally in pregnancies complicated by PPROM.

PMID- 17191263
TI  - Venlafaxine induces P-glycoprotein in human Caco-2 cells.
AB  - PURPOSE: The objective of this study was to evaluate the effect of a treatment
      with venlafaxine on the expression of multidrug resistance-associated protein
      (MRP) gene and multidrug resistance-related proteins (MDR) in human colon
      carcinoma cells (Caco-2) compared to a known P-glycoprotein (PGY1) inducer,
      rifampine. METHODS: Caco-2 cells were treated with venlafaxine (50 microM, 100
      microM, 250 microM, and 500 microM) and rifampin (25 microM and 50 microM) to
      test the possible induction of MRP and MDR expression. The treatment times used
      were 1.5, 3, 6, 12, 24, 48, and 72 h. RNA was isolated from the cells, and MDR
      and MRP genes were amplified using PCR. RESULTS: Both venlafaxine and rifampine
      had the most dramatic effect at the 50 microM concentration. There was an
      increase in MDR and MRP expression in Caco-2 cells after the acute treatment
      (1.5, 3, and 6 h) with venlafaxine. These results were similar to those with
      rifampine. CONCLUSIONS: PGY1 contributes to renal and biliary elimination of
      drugs by transporting the drug out of the cell and back into the intestinal
      lumen, where drugs may be further metabolized by intestinal enzymes such as
      Cytochrome P (CYP)-450 3A4. Its function is to limit the bioavailability of
      orally administered compounds. Due to the increase in MDR and MRP gene expression
      seen after the acute treatment with venlafaxine, there could be a potential drug
      drug interaction with other medications that are metabolized via CYP450-3A4 when
      coadministered with venlafaxine.

PMID- 17191264
TI  - Major depression-related immunological changes and combination antiretroviral
      therapy in HIV-seropositive patients.
AB  - BACKGROUND: In physically healthy subjects, major depression has been associated
      with several changes in immune function. In HIV-infected subjects too, lymphocyte
      subsets changes related to psychological conditions have been described.
      OBJECTIVE: The aim of this study was to investigate the effect of major
      depression on immunological parameters in HIV-infected subjects and to examine
      the influence of different potency antiretroviral therapies on depression-related
      immunological changes. METHOD: Thirty-six HIV-infected patients with major
      depression treated with different potency antiretroviral therapies (none, double,
      triple) were compared with 77 matched non-depressed HIV controls with regard to
      demographic, clinical and immunological parameters. RESULTS: The presence of
      depression was a significant predictor of natural killer (NK) cell number and
      percentage decline. Antiretroviral therapy and depression-antiretroviral therapy
      interaction do not significantly influence depression-related NK cell changes.
      CONCLUSIONS: The study confirms the role of depression in influencing the immune
      response in HIV-seropositive subjects and suggests that antiretroviral therapies
      may not be able to hamper the depression-related NK cell changes even using the
      most potent regimens such as Highly Active Antiretroviral Therapy (HAART).

PMID- 17191265
TI  - Lower weight gain with the orally disintegrating olanzapine than with standard
      tablets in first-episode never treated psychotic patients.
AB  - OBJECTIVE: A post-hoc analysis of the data from a randomised clinical trial
      involving prescription of antipsychotic treatment to never treated first-onset
      psychotic patients was used to compare the weight change after 6-week olanzapine
      treatment (standard tablets vs. orally disintegrating formulation). METHOD: In
      the subgroup of 38 patients randomised to olanzapine, standard olanzapine tablets
      were non-randomly and consecutively prescribed to the first 19 patients, with the
      orally disintegrating formulation being prescribed to the following 19 patients.
      RESULTS: After 6-week treatment with olanzapine, a significant higher increase in
      weight was noted in those patients on standard tablets (mean weight increase 6.3
      +/- 1.9 Kg) as compared to those on orally disintegrating olanzapine (mean weight
      increase 3.3 +/- 3.2 Kg) (F = 7.7; p = 0.009). BMI increase was also
      significantly higher in the olanzapine tablet group (mean increase of 2.1 Kg/m(2)
      as compared with 1.1 Kg/m(2) in the orally disintegrating group) (F = 4.7; p =
      0.036). Substantial weight gain (SWG) (> or =7% increase from baseline weight)
      was noted in 84.2% (n = 16) of the olanzapine tablet patients and in 31.6% (n =
      6) of the orally disintegrating olanzapine patients, with the olanzapine tablet
      group showing a significant increase in the mean percentage of weight gain (F =
      4.0; p = 0.014). CONCLUSIONS: Partial sublingual absorption occurring with orally
      disintegrating olanzapine may bypass gastrointestinal metabolisation and hence
      lead to differences in metabolite versus parent compound ratios. However, the
      need arises to replicate the present study with a longer follow-up.

PMID- 17191266
TI  - Effects of adjunctive antidepressant therapy with quetiapine on clinical outcome,
      quality of sleep and daytime motor activity in patients with treatment-resistant
      depression.
AB  - OBJECTIVE: To investigate the effects of antidepressant therapy plus quetiapine
      on major depression, motor activity, daytime sleepiness and quality of sleep.
      METHODS: Patients (N = 27) with major depressive disorder received a standard
      antidepressant treatment (Venlafaxine, Escitalopram) plus flexible dose of
      quetiapine. Patients' depression was monitored with HAM-D-21, motor activity was
      continuously measured with actigraphy and sleep parameters with the Pittsburgh
      Sleep Quality Index (PSQI) over 4 weeks. RESULTS: Whereas depression, quality of
      sleep and daytime sleepiness showed a significant improvement over 4 weeks,
      change of daytime motor activity was significant only between the wash out period
      and the last 2 days of the study. Repeated measures of variance indicate an
      independent influence of quetiapine on improved depression, motor activity and
      sleep. While we found only a mild decrease of daytime sleepiness during the first
      week of treatment, the further decline of daytime sleepiness got significant
      after 2 weeks of treatment with quetiapine, even at high mean daily doses and
      despite the sedative effects of quetiapine. CONCLUSIONS: Antidepressant treatment
      plus quetiapine is possibly a suitable treatment strategy to improve clinical
      depression, quality of sleep and motor activity. Future research is needed to
      understand the pharmacological interactions between antidepressants and
      quetiapine in major depression.

PMID- 17191267
TI  - Possible predictors of response to clonazepam augmentation therapy in patients
      with protracted depression.
AB  - INTRODUCTION: Clonazepam has been shown to be an effective supplementary
      treatment for depression. Thus, it would be useful to determine which patient
      characteristics are associated with response to clonazepam. AIMS: The purpose of
      this study was to examine the possible predictors of response to clonazepam in
      the treatment of depression. METHOD: A retrospective cohort analysis was carried
      out in 120 patients with protracted depression who were being treated with
      clonazepam. RESULTS: A variety of clinical factors, including age, gender, type
      of depression, frequency of episodes, family history; and daily dose of
      clonazepam, were analyzed as possible predictors of response to clonazepam. A
      Weibull regression analysis showed that the factors that best predicted
      improvement with clonazepam augmentation were negative family history of
      psychiatric illness (e(coef) = 0.378), daily clonazepam dose of 2.5-4.0 mg
      (e(coef) = 0.160), and unipolar depression (e(coef) = 0.147). CONCLUSIONS: These
      factors should be considered when clonazepam augmentation therapy is selected for
      protracted depression.

PMID- 17191268
TI  - Clinical correlates of clozapine prescription for schizophrenia in China.
AB  - AIMS: Few studies have investigated the prescription patterns of clozapine in
      outpatients with schizophrenia in China. It is an important issue due to
      clozapine's high efficacy and potentially fatal side effect profile. This study
      examined the use of clozapine and its correlates in China. METHODS: Three hundred
      ninety-eight clinically stable outpatients with schizophrenia were randomly
      selected and interviewed in Hong Kong (HK) and Beijing (BJ). Assessment
      instruments included the Structured Clinical Interview for DSM-IV, Brief
      Psychiatric Rating Scale, Simpson and Angus Scale of Extrapyramidal Symptoms,
      Barnes Akathisia Rating Scale and the Hong Kong and Mainland China World Health
      Organization Quality of Life Schedule-Brief version. Assessments were performed
      by the same investigator in both sites. RESULTS: Clozapine was prescribed to
      15.6% of (n = 62) patients. There was a wide inter-site variation between HK and
      BJ. Use of clozapine was associated with age, age at onset, extrapyramidal side
      effects (EPS), having health insurance, use of depot and typical antipsychotic
      and anticholinergic drugs and benzodiazepines as well as history of suicidal
      attempts. On multiple logistic regression analysis, the number of
      hospitalizations, site (HK vs. BJ), use of typical antipsychotics, polypharmacy
      and co-prescription with anticholinergics were significantly associated with the
      prescription of clozapine. No significant differences were found between the
      clozapine and non-clozapine groups with regard to any of the quality of life
      domains. CONCLUSION: A combination of economical and clinical factors, health
      policies and the characteristics of the treatment settings plays important roles
      in determining clozapine use. Clozapine appears to have little significant
      influence on quality of life in clinical stable Chinese patients with
      schizophrenia.

PMID- 17191269
TI  - The effect of histone deacetylase inhibitor trichostatin A (TSA) on the
      incorporation of 32P (Pi) and 3H-palmitic acid into the phospholipids of
      Tetrahymena.
AB  - Histone deacetylases (HDACs) are able to control also the acetylation of tubulin.
      In the present experiments the effect of trichostatin A (TSA), a HDAC inhibitor
      was studied on the incorporation of 3H-palmitic acid and 32P to the phospholipids
      (PI, PIP, PS, PC, PA, PE) of Tetrahymena pyriformis, considering earlier
      observations on the microtubular system's influence on signalling in this
      unicellular eukaryote. Treatment with 1, 5, or 10 microM TSA was studied. The
      incorporation of hydrophobic tail component, palmitic acid was inhibited in a
      concentration dependent manner into all the phospholipids, except for PA, where
      the incorporation was increased. 32P incorporation was also inhibited. The
      possible relation between the microtubular system and signalling is discussed.

PMID- 17191271
TI  - Multilevel models for estimating incremental net benefits in multinational
      studies.
AB  - Multilevel models (MLMs) have been recommended for estimating incremental net
      benefits (INBs) in multicentre cost-effectiveness analysis (CEA). However, these
      models have assumed that the INBs are exchangeable and that there is a common
      variance across all centres. This paper examines the plausibility of these
      assumptions by comparing various MLMs for estimating the mean INB in a
      multinational CEA. The results showed that the MLMs that assumed the INBs were
      exchangeable and had a common variance led to incorrect inferences. The MLMs that
      included covariates to allow for systematic differences across the centres, and
      estimated different variances in each centre, made more plausible assumptions,
      fitted the data better and led to more appropriate inferences. We conclude that
      the validity of assumptions underlying MLMs used in CEA need to be critically
      evaluated before reliable conclusions can be drawn.

PMID- 17191270
TI  - Controlled trial of dementia training with a peer support group for aged care
      staff.
AB  - OBJECTIVE: This study evaluated the impact of an eight-session training program
      for aged care staff in managing dementia-related challenging behaviours.
      Participation in the training program with an additional five-session peer
      support group was compared with both participation in training only and a wait
      list control condition. METHODS: Outcomes were evaluated for 90 participating
      staff members and 113 residents with challenging behaviours from six aged care
      facilities. Measures of staff attitudes and the behaviours of staff and residents
      were collected pre- and post-intervention, and at six month follow-up. RESULTS:
      Staff members in both dementia training groups reported improved attitudes
      regarding their knowledge and skills in managing residents with challenging
      behaviours, immediately after the training and six months later. Facility
      supervisors rated the nursing performance of trained staff more positively,
      particularly those who participated in a peer support group. The dementia
      training programs, whether with or without the inclusion of peer support, did not
      impact on levels of staff burnout or substantially reduce the level of
      challenging behaviours among aged care residents. CONCLUSIONS: While training
      programs may impact positively on staff performance, organisational
      characteristics of aged care facilities, including low levels of management
      support for staff training initiatives, limit the potential outcomes.
      Methodological limitations are discussed.

PMID- 17191272
TI  - A re-examination of distance as a proxy for severity of illness and the
      implications for differences in utilization by race/ethnicity.
AB  - The study analyzes the hospitalization patterns of elderly residents to examine
      whether the relation between distant travel and severity of illness is uniform
      across racial/ethnic subgroups. A hypothesis is made that severity thresholds
      could be higher for minorities than whites. Hospital discharge data from the
      Healthcare Cost and Utilization Project (HCUP-SID) of the Agency for Health Care
      Research and Quality for New York residents is used, with a link to the Area
      Resource File and American Hospital Association's survey files. Logistic models
      compare the association of distant admission with severity corresponding to each
      local threshold level, race, and type of hospital admission. The study uses four
      discrete distance thresholds in contrast to recent work. Also, an examination of
      severity thresholds for distant travel for different types of admission may
      clarify different sources of disparities in health care utilization. The findings
      indicate that minorities are likely to have higher severity thresholds than
      whites in seeking distant hospital care, although these conclusions depend on the
      type of condition. The study results imply that if costly elective services were
      regionalized to get the advantages of high volume for both cost and quality of
      care, some extra effort at outreach may be desirable to reduce disparities in
      appropriate care. Published in 2006 by John Wiley & Sons, Ltd.

PMID- 17191273
TI  - Redox regulation of proliferation of lens epithelial cells in culture.
AB  - Both oxidants and antioxidants have been shown to modulate cell proliferation. We
      studied the effects of hydrogen peroxide and two antioxidants on the rate of
      proliferation of lens epithelial cells in culture. Hydrogen peroxide at
      concentrations higher than 32 microM caused a significant inhibition of
      proliferation. However, in the concentration range of 0.01-0.5 microM, hydrogen
      peroxide stimulated the rate of proliferation. The effect of hydrogen peroxide
      was dependent on the amount of cells in an individual culture well, indicating
      decomposition of hydrogen peroxide by cellular enzymes. In order to eliminate the
      possibility of decomposition of the dose of hydrogen peroxide given as a bolus,
      we induced continual production of hydrogen peroxide by adding glucose oxidase to
      the incubation medium. We found that hydrogen peroxide, generated by 1-50 microU
      x ml(-1) of glucose oxidase significantly increased the rate of cell
      proliferation. This effect was most apparent at the beginning of the exponential
      phase of cellular growth. Glucose oxidase alone (100-500 microU x ml(-1)) did not
      produce any effect. The effects of pro-oxidative hydrogen peroxide were compared
      with the effects of two biologically important antioxidants, alpha-tocopherol and
      retinol. Both antioxidants completely inhibited proliferation at concentrations
      of 30 microM and higher. In contrast to retinol, the effect of alpha-tocopherol
      was dependent on the amount of cells, indicating cellular decomposition of alpha
      tocopherol. The results document the possibility of redox regulation of cellular
      proliferation at physiologically relevant reactant concentrations.

PMID- 17191276
TI  - Anniversaries old and new.

PMID- 17191274
TI  - Erythrocyte sodium pump stimulation by ouabain and an endogenous ouabain-like
      factor.
AB  - Cardiac glycosides inhibit the sodium pump. However, some studies suggest that
      nanomolar ouabain concentrations can stimulate the activity of the sodium pump.
      In this study, using the Na(+)/K(+)-ATPase of human erythrocytes, we compared the
      effect of digoxin, ouabain and an ouabain like-factor (OLF), on (86)Rb uptake.
      Ouabain concentrations below 10(-9) M significantly stimulate Rb(+) uptake, and
      the maximal increase above base-line values is 18 +/- 5% at 10(-10) M ouabain. No
      stimulation is observed in the same conditions by digoxin. OLF behaved like
      ouabain, producing an activation of Rb(+) flux at concentrations lower than 10(
      9) M ouabain equivalents (14 +/- 3% at 10(-10) M). Western blot analysis revealed
      the presence of both alpha(1) and alpha(3) pump isoforms in human erythrocytes.
      Our data confirm the analogies between OLF and ouabain and suggest that
      Na(+)/K(+)-ATPase activation may be related to the alpha(3) isoform. In addition,
      we investigated whether ouabain at different concentrations was effective in
      altering the intracellular calcium concentration of erythrocytes. We found that
      ouabain at concentration lower than 10(-9) M did not affect this homeostasis.

PMID- 17191277
TI  - Use of poly(vinyl alcohol)-coated capillaries for separation of amino-terminated
      polyamidoamine dendrimers.
AB  - Characterization of amino-terminated polyamidoamine dendrimers by CE suffers from
      a lack of resolution for higher generations and poor between-day reproducibility
      of retention times. Under optimal conditions of temperature, voltage, and sample
      amount, 0-5 generations of dendrimers could be resolved with a bare fused-silica
      capillary. However, reproducibility was poor due to potential interactions of the
      polycationic dendrimers with the uncoated quartz capillary wall. Use of a
      poly(vinyl alcohol)-coated capillary significantly decreased the migration times
      of the nanomolecules without compromising resolution. Dendrimer mixtures
      containing generations 0-5 are separated as discrete, nonoverlapping peaks in
      about 15 min. In addition, the between-day precision of retention times was
      dramatically improved without the need for internal standards or data
      normalization. Dendrimers of various generations and cores run on different days
      showed an RSD of retention times of less than 4%. The poly(vinyl alcohol) coating
      was very stable as shown by the excellent precision of migration times obtained
      on a capillary used for a month with more than 100 injections. Similar to PAGE,
      separation of polyamidoamine dendrimers on a bare fused-silica and poly(vinyl
      alcohol)-coated capillary showed an exponential relationship between migration
      times and calculated charge density of the nanomolecules.

PMID- 17191278
TI  - Simulation of DNA electrophoresis through microstructures.
AB  - The dependence of the mobility of DNA molecules through an hexagonal array of
      micropillars on their length and the applied electric field was investigated and
      it was found that mobility is a nonmonotonic function of their length. Results
      also revealed that the size dependence of the DNA mobility depends on the applied
      electric field and there is a crossover around E approximately 25 V/cm for the
      mobility of lambda-DNA and T4-DNA. These observations are explained in terms of
      the diffusion process inside the structure affected by the solvent and are
      modeled using the Langevin and its corresponding Fokker-Planck equations. The
      phenomenon is generalized under three regimes in a phase diagram relating the
      electric field and the DNA lengths. The model and the associated phase diagram
      described here provide an explanation for the conflicting results reported by
      previous authors (Han et al. on the one hand, and Duong et al. and Inatomi et al.
      on the other) about the dependence of mobility on the DNA size in lattices near
      or below the radius of gyration.

PMID- 17191279
TI  - Construction of an antibody microarray based on agarose-coated slides.
AB  - The antibody microarray, a high-throughput multiplex immunoassay method, has
      become a significant tool for quantitative proteomics studies. We describe here
      the strategies for optimizing the condition of antibody microarray building based
      on agarose-coated slides. In this study, modified glass slides were robotically
      printed with capture antibodies against monocyte chemoattractant protein 1 (MCP
      1), then dilutions of the cytokine were applied to the arrays, and the protein
      was detected with biotin-labeled antibody coupled with Cy3-conjugated
      streptavidin. Thus a protein profiling microarray based on sandwich immunoassay
      has been established. Various factors in the production of antibody microarrays
      were analyzed: the capture antibody concentrations, shelf life of the
      postprinting slides, blocking buffers, and reproducibility of the system. A
      calibration curve with a correlation coefficient of 0.9995 was established which
      suggested that the matrix can retain arrayed proteins in near-quantitative
      fashion. The results revealed high signal uniformity and reproducibility with
      regard to intra-array (1.3%) and the interarray (8.7%) variation at the capture
      antibody concentration of 125 microg/mL. Besides, the printed arrays could be
      stored for at least two months without any apparent change of the performance
      parameters.

PMID- 17191280
TI  - Rapid characterization of alkylpolyphosphonates by CZE with indirect photometric
      and mass spectrometric detection.
AB  - Methods for the rapid characterization of industrial alkylpolyphosphonates (APPs)
      by infusion MS and CZE with indirect photometric (IPD) and MS detection are
      described. Technical-grade APPs, including alkylaminepolyphosphonates with 3-5
      phosphonate groups and different hydrocarbon skeletons, hydroxyethyl-amino
      bis(methylenephosphonic acid), hydroxyethylidene-diphosphonic acid, and 2
      phosphonobutane-1,2,4-tricarboxylic acid, were examined. A 10 mM solution of
      adenosine triphosphate disodium salt at pH 2.2 was used as BGE. The nominal
      compounds of the industrial APPs and their impurities were well resolved in less
      than 15 min. The peaks were identified by using extracted ion electropherograms,
      which were obtained at the m/z values indicated by the peaks of the infusion
      spectra. Low concentrations of esters, anhydrides, and APPs having different
      hydrocarbon skeletons compared to nominal compounds, and lacking phosphonate and
      methylene-phosphonate groups with respect to them, were found. Also, hydroxyethyl
      aminobis(methylenephosphonic acid) contained an intramolecular ester at a
      concentration close to that of the nominal compound. Application of CZE-IPD and
      CZE-MS to the quality control of industrial APPs, and of CZE-MS to the
      identification and characterization of APPs in cleaning products, was
      demonstrated.

PMID- 17191281
TI  - Alkaline extraction of human plasma proteins from nondenaturing micro-2-D gels
      for protein/polypeptide mass measurement and peptide mass fingerprinting using
      MALDI-TOF MS.
AB  - Previously, we have reported a high-efficiency method of protein extraction from
      CBB-stained polyacrylamide gels for molecular mass measurement with MALDI-TOF MS
      [1]. In the present work, the alkaline extraction method was applied to CBB
      stained 2-DE gels on which human plasma proteins were separated in the absence of
      denaturant. In order to examine the performance of the method, ten spots with
      apparent molecular masses (MMapp) in the range of 65 to 1000 kDa were selected
      and the proteins were extracted from the gel pieces. The extracts were subjected
      to whole-mass measurement by MALDI-TOF MS, with and without DTT treatment. In
      addition, the extracts were subjected to in-solution trypsin digestion followed
      by MALDI-TOF MS and PMF analysis. Successful extraction of proteins from the ten
      spots, up to MMapp 1000 kDa, has been ascertained by the significant PMF
      assignment (MASCOT) with high sequence coverage of the respective proteins or
      polypeptides. When direct mass measurement of the extracted proteins was
      attempted, three spots in MMapp range 65-100 kDa provided mass peaks. Five spots
      in MMapp range 150-400 kDa did not give mass peaks of the intact proteins, but
      showed those of the constituent polypeptides after the DTT treatment. Extraction
      of proteins prior to trypsin digestion enabled the procedure of PMF analysis to
      be much simpler than the conventional in-gel digestion method, providing
      comparable protein scores and sequence coverage. The technique presented here
      suggests a new strategy for the characterization of proteins separated by
      nondenaturing 2-DE.

PMID- 17191282
TI  - Mercury speciation by CE: a review.
AB  - CE methods for the speciation of inorganic and organomercury compounds are
      reviewed. Sample preparation, separation conditions and detection modes are
      discussed. Efficient separation and sensitive determination of mercury species by
      CE typically involves complexation with various thiols, chromogenic and other
      chelating agents; however, some methods do not require complexation.
      Spectrophotometric detection based on UV-visible absorption is by far the most
      commonly used. Hyphenated techniques, such as CE/inductively coupled plasma (ICP)
      MS, hydride generation coupled to ICP-MS or atomic fluorescence spectrometry and
      CE/atomic absorption spectrometry are gaining popularity due to their high
      sensitivity and selectivity. Last, but not least, the potential and applications
      of electrochemical methods for detection of separated mercury species are
      outlined.

PMID- 17191285
TI  - Total synthesis and determination of the absolute configuration of (+)
      intricatetraol.

PMID- 17191286
TI  - Cellular inhibition of protein tyrosine phosphatase 1B by uncharged
      thioxothiazolidinone derivatives.
AB  - As important regulators of cellular signal transduction, members of the protein
      tyrosine phosphatase (PTP) family are considered to be promising drug targets.
      However, to date, the most effective in vitro PTP inhibitors have tended to be
      highly charged, thus limiting cellular permeability. Here, we have identified an
      uncharged thioxothiazolidinone derivative (compound 1), as a competitive
      inhibitor of a subset of PTPs. Compound 1 effectively inhibited protein tyrosine
      phosphatase 1B (PTP1B) in two cell-based systems: it sensitized wild-type, but
      not PTP1B-null fibroblasts to insulin stimulation and prevented PTP1B-dependent
      dephosphorylation of the FLT3-ITD receptor tyrosine kinase. We have also tested a
      series of derivatives in vitro against PTP1B and proposed a model of the PTP1B
      inhibitor interaction. These compounds should be useful in the elucidation of
      cellular PTP function and could represent a starting point for development of
      therapeutic PTP inhibitors.

PMID- 17191287
TI  - Unstable micellarization of carbon-nanotube solutions for low-loss reactivity and
      crosslinking.

PMID- 17191288
TI  - Fluorescent electrospun nanofibers embedding dye-loaded zeolite crystals.

PMID- 17191289
TI  - Metal-induced gap states at a carbon-nanotube intramolecular heterojunction
      observed by scanning tunneling microscopy.

PMID- 17191290
TI  - Multicomponent monolayer architectures at the solid-liquid interface: towards
      controlled space-confined properties and reactivity of functional building
      blocks.

PMID- 17191292
TI  - Characterisation of the binding of cationic amphiphilic drugs to phospholipid
      bilayers using surface plasmon resonance.
AB  - The interactions of three cationic amphiphilic drugs (CPZ, AMI, PROP) with
      phospholipid vesicles comprising DOPC, DMPC, or DSPC were investigated using
      surface plasmon resonance (SPR). Responses for CAD concentrations in the range
      15.625 to 1500 microM were measured. The greatest uptake by each phospholipid
      bilayer occurred with CPZ. Inclusion of CAD concentrations between 750 and 1500
      microM provided evidence for a second nonsaturable binding process, which may
      arise from intercalation of the drugs within the lipid bilayer. CAD binding was
      additionally shown to be dependent on membrane fluidity. Responses were initially
      fitted over a concentration range of 15.625 to 500 microM using a model which
      incorporated terms for a saturable binding site. This yielded very poor values of
      K(D) and nonsensible values of saturation responses. Subsequently, responses were
      fit to the expression for a model which incorporated terms for both a saturable
      binding site and second nonsaturable site. Measurable binding affinities (K(D)
      values ranged from 170 to 814 microM) were obtained for DOPC and DMPC bilayers
      which are similar to values reported previously. This work demonstrates that SPR
      studies with synthetic phospholipid bilayers provide a potentially useful
      approach for characterising drug-membrane binding interactions and for providing
      insight into the processes that contribute to drug-membrane binding.

PMID- 17191291
TI  - Understanding binding selectivity toward trypsin and factor Xa: the role of
      aromatic interactions.
AB  - A congeneric series of four bis-benzamidine inhibitors sharing a dianhydrosugar
      isosorbide scaffold in common has been studied by crystal structure analysis and
      enzyme kinetics with respect to their binding to trypsin and factor Xa. Within
      the series, aromatic interactions are an important determinant for selectivity
      discrimination among both serine proteases. To study the selectivity-determining
      features in detail, we used trypsin mutants in which the original binding site is
      gradually substituted to finally resemble the factor Xa binding pocket. The
      influence of these mutations has been analyzed on the binding of the closely
      related inhibitors. We present the crystal structures of the inhibitor complexes
      obtained by co-crystallizing an "intermediate" trypsin mutant. They could be
      determined to a resolution of up to 1.2 A, and we measured the inhibitory
      activity (K(i)) of each ligand against factor Xa, trypsin, and the various
      mutants. From these data we were able to derive a detailed structure-activity
      relationship which demonstrates the importance of aromatic interactions in
      protein-ligand recognition and their role in modulating enzyme selectivity.
      Pronounced preference is experienced to accommodate the benzamidine anchor with
      meta topology in the S(1) specificity pocket. One ligand possessing only para
      topology deviates strongly from the other members of the series and adopts a
      distinct binding mode addressing the S(1)' site instead of the distal S(3)/S(4)
      binding pocket.

PMID- 17191294
TI  - With phosphinophosphonic acids to nanostructured, water-soluble, and
      catalytically active rhodium clusters.

PMID- 17191293
TI  - Dimerizable redox-sensitive triazine-based cationic lipids for in vitro gene
      delivery.

PMID- 17191295
TI  - Solid-state interconversions of coordination networks and hydrogen-bonded salts.

PMID- 17191296
TI  - Hofmeister effects on poly(NIPAM) microgel particles: macroscopic evidence of ion
      adsorption and changes in water structure.
AB  - The term Hofmeister effects is broadly used to refer to ionic specificities in
      many different physical, chemical and biological phenomena. The origin of this
      ionic specificity is sought in two interdependent microscopic sources: 1) the
      peculiarities of the solvent structure near surfaces and around the ions, and 2)
      specific ion adsorption-exclusion mechanisms near a surface. In this work,
      Hofmeister effects on poly(N-isopropylacrylamide) [poly(NIPAM)]-based microgels
      are examined. Poly(NIPAM) particles are thermally sensitive microgels exhibiting
      volume-phase transitions with temperature. This temperature-sensitive system
      seems to be suitable for the independent observation of the two microscopic
      sources of Hofmeister effects. On the one hand, volume-phase transition,
      evaluated by photon correlation spectroscopy (PCS), gives information about how
      the presence of ions changes the water structure around the poly(NIPAM) chains.
      On the other hand, electrokinetic studies show relevant data about ionic
      adsorption-exclusion phenomena at the polymer surface.

PMID- 17191298
TI  - Solid-state NMR spectroscopy of a paramagnetic protein: assignment and study of
      human dimeric oxidized CuII-ZnII superoxide dismutase (SOD).

PMID- 17191301
TI  - Onionlike hybrid assemblies based on surfactant-encapsulated polyoxometalates.

PMID- 17191302
TI  - Electroactive nanotube membranes and redox-gating.

PMID- 17191304
TI  - Cytokeratin autoantibodies: useful serologic markers for toluene diisocyanate
      induced asthma.
AB  - To evaluate the clinical significance of autoantibodies to three major epithelial
      cytokeratins (CK)--CK8, CK18, and CK19--we compared 66 patients with toluene
      diisocyanate (TDI)-induced asthma (group I) with three control groups: 169
      asymptomatic exposed subjects (group II), 64 patients with allergic asthma (group
      III), and 123 unexposed healthy subjects (group IV). Serum IgG, specific for
      human recombinant CKs, were measured by ELISA (enzyme linked immunosorbent
      assay), and ELISA inhibition tests were performed. The existence of these
      antibodies was confirmed by IgG immunoblot analysis. Anti-TDI-HSA (human serum
      albumin) IgE and IgG antibodies were measured by ELISA in the same set of the
      patients. The prevalence of CK8, CK18, and CK19 auotantibodies in group I was
      significantly higher than in the other three groups. Results of the ELISA
      inhibition test showed significant inhibition with the addition of three CKs in a
      dose-dependent manner. No significant association was found between CK
      autoantibodies and the prevalence of anti- TDI-HSA IgG and IgE antibodies. These
      results suggest that autoantibodies to CK18 and CK19 can be used as serologic
      markers for identifying patients with TDI-induced asthma among exposed workers.

PMID- 17191305
TI  - Urachal anomalies in children: a single center experience.
AB  - The objective of this study is to define optimal diagnosis and treatment
      strategies for patients with urachal anomalies in the pediatric age group. The
      medical records of 21 children who had undergone surgery for urachal anomalies at
      Severance Hospital, Yonsei University College of Medicine from January 1990 to
      April 2005 were reviewed. The subjects included 14 males and 7 females (M:F 2:1).
      The four types of urachal anomalies confirmed were a urachal cyst in 10 patients
      (47.6%), a patent urachus in 6 (28.6%), a urachal sinus in 4 (19.0%) and a
      urachal diverticulum in 1 (4.8%) patient. The most common presenting complaint
      was umbilical discharge (n = 10, 40.0%), followed by abdominal mass (n = 9,
      36.0%). Urachal anomalies were diagnosed by ultrasonography in 18 patients, and 7
      of them were additionally examined by computed tomography. The remaining patients
      were diagnosed solely by surgical exploration. Excision was performed in all
      patients and was supplemented by partial cystectomy in three. Umbilical discharge
      was the most common clinical manifestation in our patients, suggesting that
      ultrasonography should be performed in patients with umbilical discharge to
      differentiate urachal anomalies. We found the most common anomaly to be the
      urachal cyst, and all patients were successfully treated by surgical excision.

PMID- 17191303
TI  - Kawasaki disease.
AB  - Kawasaki disease is an acute febrile, systemic vasculitic syndrome of an unknown
      etiology that primarily occurs in children younger than five years of age. The
      principal presentations of Kawasaki disease include fever, bilateral nonexudative
      conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities,
      rash, and cervical lymphadenopathy. Coronary artery aneurysms or ectasia develops
      in 15% to 25% of untreated children with the disease, which may later lead to
      myocardial infarction, sudden death, or ischemic heart disease. Treatment with
      intravenous gamma globulin (IVIG) is effective, but the mode of action is still
      unclear. The development of a diagnostic test, a more specific therapy, and
      ultimately the prevention of this potentially fatal illness in children are all
      dependent upon the continued advances in determining the etiopathogenesis of this
      fascinating disorder.

PMID- 17191306
TI  - Lack of association between polymorphisms of the dopamine receptor D4 and
      dopamine transporter genes and personality traits in a Korean population.
AB  - Human personality traits have a considerable genetic component. Cloninger et al.
      were the first to postulate that certain personality traits, such as novelty
      seeking, are related to the dopamine neurotransmitter system. In this study, we
      investigated the associations between dopamine receptor D4 (DRD4) exon III and
      dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and
      DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose
      personality traits were assessed with the Temperament and Character Inventory
      (TCI). There were no significant differences between scores of TCI temperament
      dimensions (novelty seeking, harm avoidance, reward dependence, and persistence)
      and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no
      significant association with any of the temperament subscales of the TCI. These
      data suggest that DRD4 and DAT1 gene polymorphism may not associated with
      personality traits in a Korean population.

PMID- 17191307
TI  - Efficacy and long-term follow up of combination therapy with interferon alpha and
      ribavirin for chronic hepatitis C in Korea.
AB  - Combination therapy with interferon alpha (IFN-alpha) and ribavirin for 24 or 48
      weeks according to HCV genotype has improved the overall sustained virological
      response (SVR) rates to approximately 40%. The aim of this study was to
      investigate the long-term efficacy of combination therapy with IFN-alpha and
      ribavirin for chronic hepatitis C in Koreans. One hundred thirty-eight patients
      with chronic hepatitis C who received this combination therapy between 1995 and
      2003 were analyzed retrospectively. All patients were treated with IFN-alpha 3-6
      million units three times weekly in combination with 900-1200 mg/day of ribavirin
      for 24 weeks. The overall SVR rate was 41.3%. Patients were followed up for a
      median of 41 months (range, 12-105 months) after completion of therapy. In all of
      the SVR patients (57 patients), SVR was conserved during the follow-up period.
      None of the patients progressed to decompensated liver disease or hepatocellular
      carcinoma (HCC). However, 5 of the 81 non-SVR patients (6.2%) progressed to
      decompensated liver disease or HCC. In conclusion, combination therapy with IFN
      alpha and ribavirin shows good long-term efficacy in patients with chronic
      hepatitis C in Korea, one of the highest endemic areas of hepatitis B virus (HBV)
      infection.

PMID- 17191308
TI  - The CobraPLA during anesthesia with controlled ventilation: a clinical trial of
      efficacy.
AB  - The CobraPLA (CPLA) is a relatively new supraglottic airway device that has not
      been sufficiently investigated. Here, we performed a prospective observational
      study to evaluate the efficacy of the CPLA during controlled ventilation. In 50
      anesthetized and paralyzed patients undergoing elective surgery a CPLA was
      inserted and inflated to an intracuff pressure of 60 cm H2O. The success rate of
      insertion upon the first attempt was 82% (41/50), with a mean insertion time of
      16.3 +/- 4.5 seconds. The adequacy of ventilation was assessed by observing the
      end tidal CO2 waveform, movement of the chest wall, peak airway pressure (13.5 cm
      H2O), and leak fraction (4%). We documented the airway sealing pressure (22.5 cm
      H2O) and noted that the the site of gas leaks at that pressure were either at the
      neck (52%), the abdomen (46%), or both (2%). In 44 (88%) patients, the vocal
      cords were visible in the fiberoptic view through the CPLA. There was no gastric
      insufflation during the anesthesia. Respiratory and hemodynamic parameters
      remained stable during CPLA insertion. Postoperative blood staining of CPLA was
      minimal, occurring in 22% (11/50) of patients. Mild and moderate throat soreness
      was reported in 44% (22/50) and 4% (2/50) of patients, respectively. Lastly, mild
      dysphonia was observed in 6% (3/50) of patients and mild dysphagia in 10% (5/50)
      of patients. Our results indicated that the CPLA is both easy to place and allows
      adequate ventilation during controlled ventilation.

PMID- 17191309
TI  - Endoscopic papillary balloon dilation with large balloon after limited
      sphincterotomy for retrieval of choledocholithiasis.
AB  - Endoscopic papillary balloon dilation (EBD) for choledocholithiasis is known to
      be comparable to endoscopic sphincterotomy (EST) especially in cases of small
      stones. With larger stones, EBD with conventional balloon, which have a diameter
      of 6-8 mm, was reported as less effective for extraction of stones. We evaluated
      the efficacy and complications of EBD with large balloons (10-15 mm) after
      limited EST for retrieval of choledocholithiasis. From February 2005, we have
      performed EBD with limited EST for retrieval of common bile duct (CBD) stones.
      The patients who admitted with hyperamylasemia and gallstone pancreatitis were
      excluded. In cases without CBD dilation, EPBD with 12 mm for 40 seconds was
      performed. And in cases with CBD dilation, we dilated the sphincters with 15 mm
      sized balloon for 40 seconds. Total 22 patients (11 of male) were performed EBD
      with limited EST for retrieval of CBD stones. The median diameter of the stones
      was 10 mm (5-25 mm). Ten cases had multiple stones and 6 cases periampullary
      diverticuli. Successful stone removal in the initial session of ERCP with EBD was
      accomplished in 16 patients (72.7%). And complete retrieval of bile duct stones
      was achieved in all patients with repeated ERCP. In the aspect of complications,
      any episodes of perforation, bleeding was not developed. Only one case of mild
      grade of post-procedural pancreatitis was noted. However, post-procedural
      hyperamylasemia was developed in 16 cases (68.2%). EBD with larger balloon seems
      to be a feasible and safe alternative technique for conventional EST in CBD stone
      extraction.

PMID- 17191310
TI  - The expression of estrogen receptors in hepatocellular carcinoma in Korean
      patients.
AB  - Expression of estrogen receptors (ER)-alpha and -beta, as well as androgen
      receptor (AR), in hepatocellular carcinoma (HCC) is thought to be correlated with
      prognosis, survival, and male prevalence of HCC. These hypotheses are based on
      investigations of European patients; however the expression patterns of these
      receptors in Asian patients are largely unknown. In this study, we collected
      liver carcinoma and peritumor tissues from 32 patients (9 females and 23 males)
      in South Korea. The expression of ERs and ARs was studied using RT-PCR. Wild-type
      ER-alpha and AR were expressed in all of the samples investigated, and their
      expression was independent of the causal virus or patient sex. Expression of the
      ER-alpha variant was independent of sex (100% female vs. 91.3% male) and HCV and
      HBV status (91.3% vs. 100%). Wild-type ER-beta was expressed more often in HCV
      patients than in HBV patients (95.7% vs. 44.4%; p < 0.05). In conclusion, the
      stronger ER-alpha variant expression in HCC tissues implies that this variant has
      an important role in HCC development. However, at least in Korean patients,
      expression of the ER-alpha variant (vER-alpha) is not related to male HCC
      prevalence. In addition, the predominant expression of ER-beta in HCV patients
      suggests that it plays an important role in HCV-induced liver disease.

PMID- 17191311
TI  - Bile acid analysis in biliary tract cancer.
AB  - The etiology of biliary tract cancer is obscure, but there are evidences that
      bile acid plays a role in carcinogenesis. To find the association between biliary
      tract cancer and bile acid, this study compared the bile acid concentration and
      composition among patients with biliary cancer, biliary tract stones, and no
      biliary disease. Bile was compared among patients with biliary tract cancer (n =
      26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples
      were obtained by percutaneous transhepatic biliary drainage, endoscopic
      nasobiliary drainage, or gallbladder puncture, and analyzed for cholic,
      deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition.
      Total bile acid concentration was lower in the cancer group than the biliary
      stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and
      23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6%
      and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was
      similar when disease site was limited to bile duct or gallbladder. Analysis of
      cases with bilirubin <or= 2.0 mg/dL also showed lower total bile acid
      concentration and deoxycholic acid composition in the cancer group compared to
      controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct
      obstruction explains some of the difference in total concentration and
      composition of bile acid, there are other contributing mechanisms. We suspect the
      alteration of bile acid transport might decrease bile acid excretion and cause
      the accumulation of carcinogenic bile acid in bile duct epithelium.

PMID- 17191312
TI  - Management strategy for congenital choledochal cyst with co-existing intrahepatic
      dilation and aberrant bile duct as well as other complicated biliary anomalies.
AB  - The purpose of this study was to investigate and discuss imaging methods and
      management strategies for congenital choledochal cyst with co-existing
      intrahepatic dilation and aberrant bile duct as well as other complicated biliary
      anomalies. In this study we reviewed and analyzed 72 patients with congenital
      choledochal cyst, ranging in age from 15 days to 12 years old and who were seen
      at our hospital during the past 12 years, from January 1993 to October 2005. The
      image manifestation and clinical significance of patients with co- existing
      intrahepatic biliary dilation and aberrant bile duct were carefully examined
      during operation via MRCP, cholangiography and choledochoscope. Twenty-two cases
      (30.1%) presented with intrahepatic bile duct dilation and 12 of these were of
      the cystic type. That is, the orifice of the dilated intrahepatic tract that
      converged into the common hepatic duct showed membrane or septum-like stenosis.
      In 10 cases the dilation tapered off from the porta hepatis to the initiating
      terminals of the intra-hepatic bile ducts and was not accompanied by stenosis. An
      aberrant bile duct was observed in 2 of the cases. In 3 cases, the right and left
      hepatic ducts converged at the choledochal cyst. In conclusion, the imaging
      methods for intrahepatic bile duct dilation possess important clinical
      significance. Further, for hepatojejunostomy with radical excision of a
      choledochal cyst, additional operative procedures for intrahepatic stenosis,
      possible bile duct malformation and pancreaticobiliary common duct calculi can
      potentially reduce postoperative complications.

PMID- 17191313
TI  - Surgical experiences of functioning neuroendocrine neoplasm of the pancreas.
AB  - We present our surgical experiences with functioning neuroendocrine neoplasms of
      the pancreas to define its natural history, and to suggest its proper management.
      From June 1990 to June 2005, patients with diagnosis of functioning
      neuroendocrine (islet cell) neoplasms of the pancreas were retrospectively
      reviewed. Fourteen patients (5 men and 9 women) with a median age of 49 years
      (range, 12 - 68 years) were identified. Twelve patients (86%) had insulinoma, two
      (14%) had gastrinoma. One (7%) with pancreatic insulinoma was multiple endocrine
      neoplasia type 1. Intraoperative ultrasound scan (sensitivity, 83%) was the most
      powerful modality for tumor localization. Fifteen neoplasms with median tumor
      size 1 cm (range 0-3 cm) were resected. Four insulinomas (26.7%) were located in
      the head of the pancreas and 5 (36%), in the tail. Another 5 (36%) insulinomas
      and 1 (7%) gastrinoma were located around the neck area near the SMV or PV.
      Eleven patients (79%) underwent enucleation, and 2 patients (14%), distal
      pancreatectomy with splenectomy. 100% of patients with functioning neuroendocrine
      neoplasms of the pancreas have survived. The overall disease free 10-year
      survival was found to be about 81%. Exact localization of tumor by intraoperative
      ultrasound and surgical removal are promising for good prognosis.

PMID- 17191314
TI  - A comparison of autologous and homologous transfusions in spinal fusion.
AB  - Autologous transfusion has been used to overcome adverse effects of homologous
      transfusion. Clinical studies evaluating general orthopaedic postoperative
      results have been designed to compare these transfusion methods. However, few
      studies have evaluated postoperative results in spinal fusion surgeries, which
      have larger blood loss volumes. The purpose of this study is to determine if
      there are differences in postoperative infection and clinical results of spinal
      fusion with autologous, as compared to homologous, blood transfusion. A total of
      62 patients who underwent instrumented spinal fusion and received autologous (n =
      30) or homologous (n = 32) transfusions were reviewed. Information on gender,
      age, preoperative and 3-day postoperative hematologic features, total transfused
      units, segmental estimated blood loss, transfused units, and surgery time were
      collected. In addition, postoperative infection data on wound infection,
      pneumonia, urinary tract infection, cellulitis, and viral disease, incidence and
      duration of fever, as well as clinical results, fusion rates, and patient
      feedback were collected. No differences in postoperative infection and clinical
      results were found between the two types of transfusions; however, homologous
      transfusion was associated with an increased number of total units transfused,
      longer duration of fever, and decreased patient satisfaction regarding the
      transfusion.

PMID- 17191315
TI  - Does the tibial and sural nerve transection model represent sympathetically
      independent pain?
AB  - Neuropathic pain can be divided into sympathetically maintained pain (SMP) and
      sympathetically independent pain (SIP). Rats with tibial and sural nerve
      transection (TST) produce neuropathic pain behaviors, including spontaneous pain,
      tactile allodynia, and cold allodynia. The present study was undertaken to
      examine whether rats with TST would represent SMP- or SIP-dominant neuropathic
      pain by lumbar surgical sympathectomy. The TST model was generated by transecting
      the tibial and sural nerves, leaving the common peroneal nerve intact. Animals
      were divided into the sympathectomy group and the sham group. For the
      sympathectomy group, the sympathetic chain was removed bilaterally from L2 to L6
      one week after nerve transection. The success of the sympathectomy was verified
      by measuring skin temperature on the hind paw and by infra red thermography.
      Tactile allodynia was assessed using von Frey filaments, and cold allodynia was
      assessed using acetone drops. A majority of the rats exhibited withdrawal
      behaviors in response to tactile and cold stimulations after nerve stimulation.
      Neither tactile allodynia nor cold allodynia improved after successful
      sympathectomy, and there were no differences in the threshold of tactile and cold
      allodynia between the sympathectomy and sham groups. Tactile allodynia and cold
      allodynia in the neuropathic pain model of TST are not dependent on the
      sympathetic nervous system, and this model can be used to investigate SIP
      syndromes.

PMID- 17191316
TI  - Effects of sinusoidal electromagnetic field on structure and function of
      different kinds of cell lines.
AB  - This study investigated that whether a 2 mT, 60 Hz, sinusoidal electromagnetic
      field (EMF) alters the structure and function of cells. This research compared
      the effects of EMF on four kinds of cell lines: hFOB 1.19 (fetal osteoblast), T/G
      HA-VSMC (aortic vascular smooth muscle cell), RPMI 7666 (B lymphoblast), and HCN
      2 (cortical neuronal cell). Over 14 days, cells were exposed to EMF for 1, 3, or
      6 hours per day (hrs/d). The results pointed to a cell type-specific reaction to
      EMF exposure. In addition, the cellular responses were dependent on duration of
      EMF exposure. In the present study, cell proliferation was the trait most
      sensitive to EMF. EMF treatment promoted growth of hFOB 1.19 and HCN-2 compared
      with control cells at 7 and 14 days of incubation. When the exposure time was 3
      hrs/d, EMF enhanced the proliferation of RPMI 7666 but inhibited that of T/G HA-
      VSMC. On the other hand, the effects of EMF on cell cycle distribution, cell
      differentiation, and actin distribution were unclear. Furthermore, we hardly
      found any correlation between EMF exposure and gap junctional intercellular
      communication in hFOB 1.19. This study revealed that EMF might serve as a
      potential tool for manipulating cell proliferation.

PMID- 17191317
TI  - Toxoplasma gondii inhibits apoptosis in infected cells by caspase inactivation
      and NF-kappaB activation.
AB  - Our experiments aimed to clarify the mechanism by which host cell apoptosis is
      inhibited by infection with the intracellular protozoan parasite, Toxoplasma
      gondii (T. gondii). Mouse spleen cells were cultured in 6-well plates with RPMI
      1640/ 10% FBS at 37?, in a 5% CO2 atmosphere. Apoptosis of spleen cells was
      induced by actinomycin-D (AD) treatment for 1 h prior to infection with T.
      gondii. A variety of assays were used to assess the progression of apoptosis: DNA
      size analysis on agarose gel electrophoresis, flow cytometry with annexin V/PI
      staining, and analysis of expression levels of Bcl-2 family and NF-kappaB mRNA
      and proteins by RT-PCR, Western blotting, and EMSA. Additionally, transmission
      electron microscopy (TEM) was performed to observe changes in cell morphology.
      Fragmentation of DNA was inhibited in spleen cells treated with AD and T. gondii
      5 h and 18 h post infection, respectively, and flow cytometry studies showed a
      decreased apoptotic rates in AD and T. gondii treated spleen cells. We observed
      decreased expression of Bax mRNA and protein, while levels of Bcl-2 mRNA remained
      constant in spleen cells treated with AD and T. gondii. Caspase 3 and PARP were
      inactivated in cells treated with AD and T. gondii, and increased levels of
      cleaved caspase 8 were also observed. Analysis of EMSA and Western blot data
      suggests that activation of transcription factor NF-kappaB may be involved in the
      blockade of apoptosis by T. gondii. TEM analysis showed nuclear fragmentation and
      chromatin condensation occurring in spleen cells treated with AD; however, such
      apoptosis- associated morphological changes were not observed in cells treated
      with both AD and T. gondii tachyzoites. Together, these data show that T. gondii
      infection inhibits AD induced apoptosis via caspase inactivation and NF-kappaB
      activation in mouse spleen cells.

PMID- 17191318
TI  - Clear cell basal cell carcinoma with sialomucin deposition.
AB  - Clear cell basal cell carcinoma (BCC) is a variant of BCC with a characteristic
      clear cell component that may occupy all or part of the tumor islands. Periodic
      acid-Schiff (PAS) staining for glycogen is variably positive, and mild deposition
      of sulfated mucin has been noted. However, to our knowledge, clear cell BCC with
      sialomucin deposition has not been reported. Here we report a case of clear cell
      BCC showing sialomucin deposition. The clear tumor cells stained with PAS and
      showed incomplete diastase-resistance. In addition, mucin staining with alcian
      blue was positive at pH 2.5 but not at pH 0.5.

PMID- 17191319
TI  - MR findings of fulminent leukoencephalopathy in EBV-associated hemophagocytic
      syndrome.
AB  - Various manifestations of brain involvement for patients with virus-associated
      hemophagocytic syndrome have been reported. Here, we report on the sequential
      magnetic resonance (MR) findings of acute demyelination of the entire brain with
      subsequent brain atrophy in a follow-up study of a 25-month- old boy who was
      admitted with fever and then diagnosed with infectious mononucleosis and EBV
      associated hemophagocytic syndrome. We also review other conditions that should
      be included in the differential diagnosis of this disease.

PMID- 17191320
TI  - Pure epidural cavernous hemangioma of the cervical spine that presented with an
      acute sensory deficit caused by hemorrhage.
AB  - Pure epidural cavernous hemangioma of the spine without vertebral involvement is
      rare. Due to the slow growth of this lesion, the most common symptoms are chronic
      pain, myelopathy, and radiculopathy. In our case, the patient complained of an
      acute onset sensory deficit of the C4 dermatome. An MRI revealed an epidural mass
      with an acute hematoma. Here, we report a case of a pure epidural cavernous
      hemangioma that presented with acute neurologic symptoms caused by intralesional
      hemorrhage and an acute epidural hematoma, which were demonstrated on the
      patient's MRI.

PMID- 17191321
TI  - A case of hypervascular hyperplastic nodules in a patient with alcoholic liver
      cirrhosis.
AB  - Most hypervascular nodules in a cirrhotic liver are hepatocellular carcinomas
      (HCCs); however, some are benign hypervascular hyperplastic nodules. We report a
      case of benign hypervascular hyperplastic nodules in a 41-year-old male patient
      without hepatitis B or C virus infection, with a history of alcohol abuse, and
      diagnosed with an aortic aneurysm. The dynamic computerized tomography of the
      liver demonstrated multiple nodular lesions on both liver lobes with arterial
      enhancement and delayed washout. The hepatic angiography showed multiple faint
      nodular staining of both lobes in the early arterial phase. Magnetic resonance
      imaging revealed numerous nodules showing high signals on T1 weighted images,
      with some nodules showing a low central signal portion. The clinical impression
      was HCC. The ultrasonography-guided liver biopsy, which was performed on the
      largest nodule (2.5 cm in size), revealed hepatocellular nodules with slightly
      increased cellularity, unpaired arteries, increased sinusoidal capillarization,
      and focal iron deposition. However, both cellular and cytological atypia were
      unremarkable. Although the clinical impression was HCC, the pathological
      diagnosis was hypervascular hyperplastic nodules in alcoholic cirrhosis.
      Differential diagnosis of hypervascular nodules in cirrhosis and HCC is difficult
      with imaging studies; thus, histological confirmation is mandatory.

PMID- 17191322
TI  - Pure choriocarcinoma of testis with tumor-infiltrating lymphocytes and
      granulomas.
AB  - Pure choriocarcinoma is very rare in the testes, and host immune responses
      including tumor infiltrating lymphocytes are unusual in choriocarcinoma. This
      study reports a case of pure testicular choriocarcinoma with extensive
      lymphocytic infiltrate and granulomatous inflammation. Scrotal ultrasonography
      revealed a heterogeneous, hyperechoic intratesticular mass. -human chorionic
      gonadotropin levels were elevated in a radioimmunoassay. The hemorrhagic and
      necrotic solid mass was composed of two cell populations - mononuclear
      pleomorphic cells and intimately admixed multinucleated smudged cells. The tumor
      cells were positive for cytokeratin 7, epidermal growth factor receptors, human
      placental lactogen and p57. Many inflammatory cells were present within the
      tumor. The majority of infiltrating cells were CD8-positive cytotoxic cells,
      which also expressed granzyme-B and TIA-1. The tumor cells were positive for
      FasL, but negative for Fas. Therefore, this case seemed to escape the host
      defense response to the tumor due to the loss of Fas, although the cellular host
      immune response was still active.

PMID- 17191323
TI  - Non-surgical treatment of vaginal agenesis using a simplified version of Ingram's
      method.
AB  - Non-surgical vaginal dilation is a safe and effective method for the creation of
      neovagina in the patient with vaginal agenesis. Compared to surgical methods, non
      surgical vaginal dilation has the advantage of low morbidity, the creation of a
      more physiologic vaginal milieu, and no surgical scarring. To overcome some
      technical limitations of original Frank's method, in 1981 Ingram proposed a
      modification of the technique that used dilators of gradually increasing size
      mounted on a bicycle seat stool. Although several studies have shown satisfactory
      outcomes using Ingram's method, there are some practical difficulties in making
      and handling the bicycle seat stool. This article reports a case of a 24-year-old
      woman with Mayer-Rokitansky-Kuster-Hauser syndrome whose vaginal agenesis is
      successfully treated with a simplified version of Ingram's method. This method
      uses dilators of gradually increasing size mounted on an ordinary chair instead
      of a bicycle seat stool. When necessary, the patient may use a fulcrum under the
      dilator.

PMID- 17191324
TI  - Consumer-Centered Computer-Supported Care for Healthy People. Proceedings of the
      9th International Congress on Nursing Informatics, NI2006.

PMID- 17191325
TI  - Conditions for the emergence of life on the early Earth. Papers of a discussion
      meeting at the Royal Society, 13-14 February 2006.

PMID- 17191326
TI  - Proceedings of the 19th Meeting of the European Macrophage and Dendritic Cell
      Society, Amsterdam, The Netherlands, October 6-8, 2005.

PMID- 17191327
TI  - [Management of wounds in the emergency room--Short text].

PMID- 17191328
TI  - [Hemostasis disorders in severe infections: State of the art].
AB  - The haemostatic system is greatly modified during severe infections. The early
      activation of coagulation is triggered by tissue factor expression and secondary
      fibrinolysis impaired by the upregulation of fibrinolysis inhibitors. This
      imbalance is a major cause of subsequent organ dysfunction. Natural
      anticoagulants (Tissue factor pathway inhibitor (TFPI), Antithrombin (AT), and
      Protein C (PC) are consumed or inhibited in this pathological process justifying
      a therapeutic supplementation with these inhibitors to improve sepsis-induced
      organ failure and mortality. No effect on the mortality rate could be documented
      in controlled studies using recombinant TFPI or AT concentrates but a biological
      interaction with heparin therapy could have biased the results. Treatment with
      recombinant activated PC was associated with a significant reduction in the
      mortality rate of severely ill patients. An increase in the rate of hemorrhagic
      adverse effects was observed with these compounds, justifying a strict observance
      of contraindications and of patient selection.

PMID- 17191329
TI  - Is health in office buildings related only to psychosocial factors?

PMID- 17191330
TI  - Information alongside medicines.

PMID- 17191331
TI  - Treatment of venoocclusive disease after liver transplantation.

PMID- 17191332
TI  - Following patients for tumor recurrence after radiofrequency ablation.

PMID- 17191333
TI  - Microbial colonization of tourniquets.

PMID- 17191334
TI  - [Every puncture reaches a meridian. Acupuncture is never "just a placebo"!].

PMID- 17191335
TI  - Environmental lead levels related to increased death.

PMID- 17191336
TI  - Can plant transposable elements generate novel regulatory systems?

PMID- 17191337
TI  - Absence in monocotyledonous plants of the diffusible plant factors inducing T-DNA
      circularization and vir gene expression in Agrobacterium.
AB  - T-DNA circularization is one of the molecular events specifically induced in
      agrobacterial cells upon their infection of dicotyledonous plant cells. We
      developed a seedling co-cultivation procedure to determine whether or not
      monocotyledonous plants have the ability to induce T-DNA circularization and vir
      gene expression. Co-cultivation of Agrobacterium tumefaciens with seedlings of
      dicotyledonous plants showed that the circularization event takes place
      efficiently. The exudates and extracts of the seedlings also effectively induced
      T-DNA circularization and vir gene expression, indicating that dicotyledonous
      seedlings contain diffusible factors capable of inducing these molecular events.
      In contrast, neither T-DNA circularization nor vir gene expression was detectable
      when Agrobacterium was incubated with seedlings of monocotyledonous plants.
      Supplementing with acetosyringone, a known inducer of vir gene expression and T
      DNA circularization, resulted in the induction of circularization during co
      cultivation with moncotyledonous seedlings. These results indicate that the
      seedlings of monocotyledonous plants have no detectable amounts of diffusible
      inducers, unlike dicotyledonous seedlings. Therefore, it is unlikely that the vir
      genes are expressed in Agrobacterium inoculated in monocotyledonous plants. This
      may be one of the blocks in tumorigenesis of monocotyledonous plant by
      Agrobacterium.

PMID- 17191338
TI  - Molecular cloning and physical characterization of a Brassica linear
      mitochondrial plasmid.
AB  - A linear mitochondrial plasmid reported to be associated with cytoplasmic male
      sterility in the genus Brassica was analyzed. A protein was found to be
      associated with the 5' ends of the plasmid. The entire plasmid was cloned by the
      homopolymer tailing technique via free hydroxyl groups present at its 3' ends.
      DNA sequence analysis of the cloned plasmid revealed a perfect terminal inverted
      repeat of 325 base pairs. Southern hybridization and restriction enzyme mapping
      analysis confirmed colinearity of the native plasmid and the clone, which showed
      significant homology with organelle DNA but not with nuclear DNA. Under high
      stringency hybridization conditions, an internal 4.6 kb fragment of the 11.5 kb
      plasmid hybridized to the main mitochondrial genome in several species. Although
      the hybridization signal was weaker, the chloroplast genome also showed homology
      to the mitochondrial plasmid. The plasmid was undetectable at a molar ratio of
      less than 1/10 000 of the main mitochondrial genome in some lines of Brassica and
      Raphanus that contain the Ogura male sterile cytoplasm (cms). The absence of the
      plasmid in these sterile lines demonstrates that the plasmid is not required for
      the expression and maternal inheritance of male sterility.

PMID- 17191339
TI  - The structure and light-dependent transient expression of a nuclear-encoded
      chloroplast protein gene from pea (Pisum sativum L.).
AB  - A nuclear gene encoding a light-induced transiently expressed protein that is
      localized in the chloroplast has been isolated from an EMBL3 library of pea DNA.
      The gene is a member of a multigene family. The sequence of the gene contains the
      complete reading frame of previously characterized cDNA clones and two introns in
      the 5' region of the protein coding sequence. Primer extension and S1 nuclease
      studies have defined the cap site. Two TATA boxes are found 5' to the initiating
      methionine codon. Only a limited homology is found between the presequence of the
      gene and transit sequences of other previously sequenced precursors. Isolated
      nuclei of pea have been labelled and the in vitro synthesized transcripts
      analysed. The results show that the light-dependent expression of the gene family
      is regulated at the level of transcription.

PMID- 17191340
TI  - Rapid chloroplast segregation and recombination of mitochondrial DNA in Brassica
      cybrids.
AB  - Brassica cybrids were obtained after fusing protoplasts of fertile and
      cytoplasmic male sterile (CMS) B. napus lines carrying the original B. napus, and
      the Ogura Raphanus sativus cytoplasms, respectively. Iodoacetate treatment of the
      fertile line and X-irradiation of the CMS line prevented colony formation from
      the parental protoplasts. Colony formation, however, was obtained after
      protoplast fusion. Hybrid cytoplasm formation was studied in 0.5 g to 5.0 calli
      grown from a fused protoplast after an estimated 19 to 22 cell divisions.
      Chloroplasts and mitochondria were identified in the calli by hybridizing
      appropriate DNA probes to total cellular DNA. Out of the 42 clones studied 37
      were confirmed as cybrids. Chloroplasts in all of the cybrid clones were found to
      derive from the fertile parent. Mitochondrial DNA (mtDNA) segregation was
      complete in some but not all of the clones. In the cybrids, mtDNA was different
      from the parental plants. Physical mapping revealed recombination in a region
      which is not normally involved in the formation of subgenomic mtDNA circles. The
      role of treatments used to facilitate the recovery of cybrids, and of organelle
      compatibility in hybrid cytoplasm formation is discussed.

PMID- 17191341
TI  - Protein-DNA interaction within one cloned chloroplast DNA replication origin of
      Chlamydomonas.
AB  - A partially purified algal protein mixture which supports in vitro DNA
      replication consists of soluble proteins and proteins extracted from thylakoid
      membrane. The membrane extract is essential for the specific initiation of
      replication at a displacement loop (D-loop) site previously mapped by electron
      microscopy. D-loop site and its flanking sequences have been cloned and
      sequenced. In this study, fragment-retention assays using various subclones of
      the sequenced region indicate that some proteins in the membrane extract bind
      strongly and specifically with a 494 bp restriction fragment which partially
      overlaps the D-loop site. Protein gel analyses of the protein-DNA complex
      identify three DNA-binding polypeptides with apparent molecular weights of 18, 24
      and 26 kDA, respectively. Treatment with chloramphenicol, an inhibitor of
      chloroplast protein synthesis, for 1 h has no obvious effect on the contents of
      the 24 or 26 kDa polypeptides but significantly reduces the content of the 18 kDa
      polypeptide in the membrane extract.

PMID- 17191342
TI  - Gene expression in archaebacteria: physical mapping of constitutive and UV
      inducible transcripts from the Sulfolobus virus-like particle SSV1.
AB  - The transcription of the genome of the UV-inducible Sulfolobus virus-like
      particle SSV1 was studied. Eight different transcripts could be distinguished by
      Northern analysis that were present in uninduced cells and the coordinately
      increased in amount after UV induction of SSV1. Using single-stranded DNA probes
      from different parts of the genome, the approximate map positions of these RNAs
      and the directions of transcription were determined. In two cases, terminator
      read-through resulted in the formation of more than one RNA species from a single
      5' end and therefore the eight different RNAs corresponded to only five different
      transcriptional starts. Two RNAs sharing a common 5' end encode SSV1 structural
      proteins. The 5' end of these transcripts was determined by S1 nuclease analysis.
      About 20 nucleotides upstream of the transcriptional start of these RNAs, there
      is an AT-rich region resembling putative promoter sequences which have been found
      at a similar distance 5' to the genes encoding stable RNAs in Thermoproteus. In
      addition to the eight constitutive transcripts, a UV-inducible RNA of 0.3 kb was
      mapped on the SSV1 genome. In contrast to all other RNAs, it was not detectable
      in uninduced cells and it is expressed shortly before the amplification and
      packaging of the SSV1 genome commences.

PMID- 17191343
TI  - Tn10 mutagenesis in Azotobacter vinelandii.
AB  - The tetracycline-resistant transposon Tn10 and its "high-hopper" derivative
      Tn10HH104 were introduced into the Azotobacter vinelandii genome using suicide
      conjugative plasmids derived from pRK2013. Several types of mutants induced by
      either of these elements are described. Nif- mutants (deficient in nitrogen
      fixation) were easily isolated, whereas the isolation of other mutant types
      (auxotrophs, sugar non-users) required special selection conditions. The
      characterization of the mutations as transposon insertions was often complicated
      and sometimes required a combination of genetic and physical tests. A common
      source of complication, the existence of double inserts, was found among the
      mutants induced by Tn10HH104 but not among those induced by Tn10. Both the high
      hopper and the wild-type element proved to undergo secondary transpositions,
      albeit at different frequencies. Another type of complication, the existence of
      heterozygotes, occurred because of the high level of redundancy of the A.
      vinelandii genome.

PMID- 17191344
TI  - Identification of a transposon-like insertion in a Glu-1 allele of wheat.
AB  - The Glu-1 locus, present on the long arms of the group 1 chromosomes of wheat,
      codes for a group of storage protein polypeptides termed high molecular weight
      (HMW) subunits of glutenin. Hexaploid wheat varieties carry a 'silent' Glu-1y
      allele on chromosome 1A, no polypeptide being attributable to this locus. When
      two such alleles from different varieties were compared, one was found to contain
      an 8 kb insertion of DNA, termed Wis-2, interrupting the coding sequence. The
      insertion site is flanked by a 5 bp duplication. The two ends of Wis-2 contain
      similar sequences over 500 bp long and its termini contain almost the same short
      sequences but in opposite orientation. These terminal sequences are related to
      those of several 'retroposon'-type transposable elements found in other
      organisms.

PMID- 17191346
TI  - Identification of a female-sterile mutation affecting yolk protein 2 in
      Drosophila melanogaster.
AB  - The three yolk proteins (YP1, YP2 and YP3) of Drosophila melanogaster are
      synthesised in the fat body and ovarian follicle cells and selectively
      accumulated in the developing oocytes to provide a nutrient source for
      embryogenesis. We have described the phenotype of a temperature-sensitive female
      sterile mutant, fs (1) K313, nad characterised its yolk proteins. This mutation
      affects the secretion of YP2 and is the first mutation affecting YP2 to be
      described. Using genetic and molecular tests we argue that the female-sterile
      phenotype results, at least in part, from the abnormal secretion of YP2
      perturbing the follicle cell secretory pathway in general and thus causing
      defects in chorion protein secretion. The gene coding for YP2 in fs (1) K313 has
      been cloned and sequenced. Two amino acid substitutions have been found which
      probably cause the abnormal secretion of YP2 and the resulting female-sterile
      phenotype.

PMID- 17191345
TI  - Chloroplast genome characterization in the red alga Griffithsia pacifica.
AB  - It has been suggested that cyanobacteria served as the ancestors for rhodophytic
      algae whose chloroplasts contain chlorophyll a and phycobilins, and that a
      rodophyte served as the plastid source for chromophytic plants that contain
      chlorophylls a and c. Although organellar DNA has been used to assess
      phylogenetic relatedness among terrestrial plants and green algae whose
      chloroplasts contain chlorophylls a and b, few data are presently available on
      the molecular profile of plastid DNA in chromophytes or rhodophytes. In this
      study the chloroplast genome of the rhodophytic, filamentous alga Griffithsia
      pacifica has been characterized. DNA was purified from isolated chloroplasts
      using protease k treatment and sodium dodecyl sulfate lysis followed by density
      centrifugation in Hoechst-33258 dye-CsCl gradients. Single and double restriction
      enzyme digests demonstrate that the DNA prepared from purified chloroplasts has a
      genome size of about 178 kilobase pairs (kb). A restriction map of this
      chloroplast genome demonstrates that it is circular and, unlike the chloroplast
      DNA (cpDNA) in most other plants, contains only a single ribosomal DNA operon.
      DNA was also purified from the mitochondria that co-isolated with chloroplasts.
      Mitochondrial DNA consists of molecules that range in size from 27 to 350 kb
      based on restriction endonuclease digestion and electron microscopic analysis.

PMID- 17191347
TI  - Are telemedicine units a medical device?

PMID- 17191348
TI  - Bar-coded patient ID: review an organizational approach to vendor selection.

PMID- 17191349
TI  - The CNO and "techies": a dynamic duo.

PMID- 17191351
TI  - Fundamental problems lie ahead in the drug discovery and commercialization
      process: restructuring of the pharmaceutical industry and an improved partnership
      with academia are required.

PMID- 17191350
TI  - [SOR SAVOIR PATIENT Cancer and fatigue. Information dedicated to cancer patients
      and relatives].
AB  - In response to the evolution of the information-seeking behaviour of patients and
      concerns from health professionals regarding cancer patient information, the
      French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced,
      in 1998, an information and education program dedicated to patients and
      relatives,the SOR SAVOIR PATIENT program. The methodology of this program adheres
      to established quality criteria regarding the elaboration of patient information.
      Cancer patient information, developed in this program, is based on clinical
      practice guidelines produced by the FNCLCC and the twenty French regional cancer
      centres, the National League against Cancer, The National Cancer Institute, the
      French Hospital Federation, the National Oncology Federation of Regional and
      University Hospitals,the French Oncology Federation of General Hospitals, many
      learned societies, as well as an active participation of patients, former
      patients and caregivers. The handbookSOR SAVOIR PATIENT Cancer and Fatigue is an
      adapted version of different publications regarding fatigue in oncology. It is
      meant to provide a basis for the explanationof the disease and to facilitate
      discussions with the healthcare team. It is available from the FNCLCC (101, rue
      de Tolbiac, 75013 Paris, Tel. (0033) 1, 01 76 64 78 00,www.fnclcc.fr). This
      document has been validated at the end of 2005 and published in January 2006. SOR
      SAVOIR PATIENT guides are systematically updated when new research becomes
      available. This article is extract from the handbook SOR SAVOIR PATIENT Cancer
      and Fatigue and concerns the causes and effects of fatigue and how to cope with
      fatigue. This information allow patients to better understand the causes and
      effects of fatigue, how to cope fatigue...which represent important patient
      information needs. This article is meant to inform patients and relatives about
      the disease and its treatments. It also offers health professionals a synthetic
      evidence-based patient information source which facilitates discussions with the
      patient.

PMID- 17191352
TI  - [Recommendation for clinical practice: use of PET-FDG in cancer of the kidney,
      prostate, testicles, and the urinary bladder].

PMID- 17191353
TI  - On the road towards strategic application of therapeutic drug monitoring of
      mycophenolic acid in renal allograft recipients.

PMID- 17191354
TI  - Population-specific limited sampling strategies for therapeutic drug monitoring
      of mycophenolic acid.

PMID- 17191355
TI  - The value of post-chemotherapy surgery for residual disease in ovarian germ cell
      tumors.

PMID- 17191356
TI  - Analysis of recent papers in hypertension.

PMID- 17191357
TI  - Second look laparotomy for ovarian germ cell tumors: to do or not to do?

PMID- 17191358
TI  - Title X in California.

PMID- 17191359
TI  - Rho GTPases and cell cycle control.
AB  - Members of the Rho family of small GTPases are crucial regulators of biological
      responses in eukaryotic cells, including cytoskeletal dynamics, cell motility and
      cell cycle progression. In the present review, we summarize our current
      understanding of the role of Rho proteins in cell cycle control, highlighting the
      contribution of specific members of the Rho family and their downstream targets
      to the regulation of key elements from the core cell cycle machinery, mostly
      involved in the G1/S transition.

PMID- 17191360
TI  - What characterizes academic radiology departments that secure large amounts of
      external funding for research?
AB  - RATIONALE AND OBJECTIVES: We sought to identify factors associated with high
      levels of external research funding in order to provide departments with
      information that may help them increase their external research funding.
      MATERIALS AND METHODS: National Institutes of Health (NIH) data on grants were
      analyzed to identify the 72 radiology departments receiving funds for diagnostic
      radiology research. A survey was sent to these departments. We placed them into
      one of three categories according to total NIH funds to the department. The
      survey asked about department characteristics such as size; breakdown of full
      time faculty among MDs, MD/PhDs, and PhDs; research space; equipment type; and
      number and types of trainees. RESULTS: Thirty-nine surveys were returned,
      including 20 from the 21 departments with the most NIH funding. PhDs played a
      larger role in the most research funding-intensive departments than in others.
      These departments also were more likely than others to give protected time to all
      MDs and to devote over 5% of clinical revenues to research, and they had a lower
      clinical workload per MD. NIH was the source of 70% of their research funding,
      The role of MD/PhDs and research space per 1000 research dollars did not vary by
      research intensity. CONCLUSIONS: These findings only demonstrate associations;
      they do not show the direction of causality. Nonetheless, they suggest what
      departments need to do if they wish to increase their external research funding.

PMID- 17191361
TI  - Tomorrow's professor: learning styles: the uniqueness of our learners.

PMID- 17191362
TI  - Penicillium marneffei infection in HIV-infected travelers.
AB  - Disseminated Penicillium marneffei infection is the third most common AIDS
      defining illness in parts of Southeast Asia. A review of the literature now shows
      that penicilliosis may represent an emergent opportunistic infection in HIV
      positive travelers to endemic regions as well.

PMID- 17191363
TI  - Hepatocyte apoptosis in hepatitis C/HIV co-infection.
AB  - Hepatocytes exposed in vitro to hepatitis C virus (HCV) and human
      immunodeficiency virus (HIV) envelope proteins and undergo apoptosis as a result
      of cell surface binding of the proteins. The studies indicate that HCV/HIV
      envelope proteins induce hepatocyte apoptosis by activating a novel downstream
      STAT1 signaling pathway.

PMID- 17191365
TI  - Bibliography. Current world literature. Immunotherapy.

PMID- 17191364
TI  - Lamotrigine-induced leucopenia.

PMID- 17191366
TI  - [General Ely and the Algerian War].

PMID- 17191367
TI  - Inorganic and organic lead compounds.

PMID- 17191368
TI  - [Agustin Albarracin Teulon (1922-2001)].

PMID- 17191369
TI  - Problematizing retrospective diagnosis in the history of disease.

PMID- 17191371
TI  - The history of disease: introduction.

PMID- 17191370
TI  - Taking accreditation to the next step.

PMID- 17191372
TI  - Comments on the round table the history of disease.

PMID- 17191373
TI  - New developments in social interdependence theory.
AB  - Social interdependence theory is a classic example of the interaction of theory,
      research, and practice. The premise of the theory is the way that goals are
      structured determines how individuals interact, which in turn creates outcomes.
      Since its formulation nearly 60 years ago, social interdependence theory has been
      modified, extended, and refined on the basis of the increasing knowledge about,
      and application of, the theory. Researchers have conducted over 750 research
      studies on the relative merits of cooperative, competitive, and individualistic
      efforts and the conditions under which each is appropriate. Social
      interdependence theory has been widely applied, especially in education and
      business. These applications have resulted in revisions of the theory and the
      generation of considerable new research. The authors critically analyze the new
      developments resulting from extensive research on, and wide-scale applications
      of, social interdependence theory.

PMID- 17191374
TI  - Signal transduction in DC differentiation: winged messengers and Achilles' heel.

PMID- 17191375
TI  - Shaping naive and memory CD8+ T cell responses in pathogen infections through
      antigen presentation.

PMID- 17191376
TI  - Understanding the role of innate immunity in the mechanism of action of the live
      attenuated Yellow Fever Vaccine 17D.

PMID- 17191378
TI  - The yin and yang of adaptive immunity in allogeneic hematopoietic cell
      transplantation: donor antigen-presenting cells can either augment or inhibit
      donor T cell alloreactivity.

PMID- 17191379
TI  - It's only innate immunity but I like it.

PMID- 17191377
TI  - The function of local lymphoid tissues in pulmonary immune responses.

PMID- 17191380
TI  - Innate tumor immune surveillance.

PMID- 17191381
TI  - Regulation of adaptive immunity by cells of the innate immune system: bone marrow
      natural killer cells inhibit T cell proliferation.

PMID- 17191383
TI  - Germinal-center-derived B-cell memory.

PMID- 17191382
TI  - Induction and maintenance of CD8+ T cells specific for persistent viruses.

PMID- 17191384
TI  - CD28 and CD27 costimulation of CD8+ T cells: a story of survival.
AB  - Although the requirement of CD28 and CD27 costimulation has been clearly
      demonstrated during primary CD8+ T cell responses and this costimulation acts by
      providing proliferation and survival cues to naive CD8+ T cells, a number of
      questions also arise from these studies. Is the requirement for CD28 and CD27
      costimulation restricted to the initiation of the immune response in the lymph
      nodes, where presumably the initial contact between naive CD8+ T cell and DC
      occurs? What is the purpose of the dramatic influx of DC to sites of inflammation
      such as the lung during influenza virus infection and the formation of
      inflammatory BALT (iBALT)?(104) Are such DC at the site of inflammation and at
      later stages of the immune response providing cytokines or costimulation to
      effector CD8+ T cells? If DC are required for optimal secondary responses (100),
      is CD28 costimulation the missing signal or is it other members of the B7:CD28
      family or TNF family? Given that a number of investigators are actively
      addressing these questions, the answers we expect will be soon to come and open
      exciting new opportunities for immune enhancement or dampening strategies and
      vaccine adjuvants.

PMID- 17191385
TI  - CD38: an ecto-enzyme at the crossroads of innate and adaptive immune responses.

PMID- 17191387
TI  - CD4+ T cells cooperate with macrophages for specific elimination of MHC class II
      negative cancer cells.

PMID- 17191386
TI  - Vascular leukocytes: a population with angiogenic and immunossuppressive
      properties highly represented in ovarian cancer.

PMID- 17191388
TI  - Receptors and pathways in innate antifungal immunity: the implication for
      tolerance and immunity to fungi.

PMID- 17191389
TI  - Faecal prevalence of extended-spectrum Beta-lactamase (ESBL)-producing coliforms
      in a geriatric population and among haematology patients.
AB  - Antimicrobial resistance to the extended-spectrum cephalosporins is increasingly
      reported worldwide. In the local setting, nosocomial infections with multi
      resistant Gram-negative bacilli are not uncommon and are a growing concern.
      However, there is limited data on the carriage rates of such organisms in the
      local setting. In May 2001, a prospective study was carried out to determine the
      enteric carriage rates of ceftazidime-resistant Gram negative bacilli (CAZ-R GNB)
      among residents of nursing homes and from in-patients of the geriatric and adult
      haematology wards of University Malaya Medical Centre. Ceftazidime-resistant Gram
      negative bacilli (CAZ-R GNB) were detected in 25 samples (30%), out of which 6
      were from nursing home residents, 5 from geriatric in-patients and 14 from the
      haematology unit. A total of 28 CAZ-R GNB were isolated and Escherichia coli (10)
      and Klebsiella pneumoniae (7) were the predominant organisms. Resistance to
      ceftazidime in E. coli and Klebsiella was mediated by extended-spectrum beta
      lactamases (ESBLs). Although the majority of the CAZ-R GNB were from patients in
      the haematology ward, the six nursing home residents with CAZ-R GNB were enteric
      carriers of ESBL-producing coliforms. Prior exposure to antibiotics was
      associated with carriage of ESBL organisms and to a lesser extent, the presence
      of urinary catheters.

PMID- 17191390
TI  - Detection of giardine gene in local isolates of Giardia duodenalis by polymerase
      chain reaction (PCR).
AB  - Giardia duodenalis is an intestinal parasite that causes diarrhoea and
      malabsorption in children. The parasite also infects AIDS patients with a weak
      immune system. A study was carried out on six local isolates of Giardia
      duodenalis (110, 7304, 6304, M007, 2002 and 6307) from faeces of Orang Asli
      patients admitted to the Gombak Hospital. WB, a reference pathogenic strain from
      human and G. muris from a wild mouse, were commercially obtained from the
      American Type Culture Collection (ATCC). All the isolates were cultured
      axenically in TYI-S-33 medium. Two sets of primers were used for the techniques:
      primers LP1 and RP1 and primers LP2 and RP2. The sets of primers amplified
      giardine gene of 171 bp and 218 bp in sizes respectively. The study showed that
      the two sets of primers could detect G. duodenalis to the genus and species level
      specifically.

PMID- 17191391
TI  - RET and p53 expression in thyroid follicular adenoma: a study of 52 cases with 14
      years follow-up.
AB  - Most previous studies on RET and p53 proteins have focused on thyroid papillary
      carcinoma. We investigated the role of RET and p53 protein expressions using
      immunohistochemistry on 52 cases of thyroid follicular adenomas and studied the
      follow-up records of these patients. The range of follow-up period was 3 to 14
      years. The patients were between 15 and 71 years of age with a median age of 34.5
      years. There were 46 females and 6 males. Except for 3 cases, all patients were
      Malays. The minimum volume of the tumour was 1000 mm3 and the maximum was 512,000
      mm3 with a median of 270,000 mm3. Eleven (21.2%) cases showed RET expression. RET
      expression was not statistically significant when cross-tabulated against sex (p
      = 0.322), ethnicity (p = 0.518), age (p = 0.466) and symptom duration (p =
      0.144). Six (11.5%) of 52 cases showed p53 immunopositivity. p53 expressions were
      also not significantly correlated to the clinical parameters above. There was no
      correlation between RET and p53 protein expressions. The only statistically
      significant finding was the association of tumour volume with duration of
      symptoms (p = 0.05). All patients are alive at the time of writing. 3 had
      recurrent goitre, 2 of these were diagnosed as colloid goitre while the third was
      a follicular lesion. One patient suffered from depression requiring anti
      depressant treatment. In conclusion, unlike papillary carcinoma in which the
      roles of ret and p53 oncogenes are known, their roles in influencing the
      behaviour of follicular adenoma has not been ascertained.

PMID- 17191392
TI  - A modified mycological medium for isolation and culture of Malassezia furfur.
AB  - A mycological medium was developed for primary isolation and culture of
      lipophilic yeasts. It was initially based on published information of nutrients
      and trace components that would promote the growth of these yeasts. It was
      subsequently modified and adjusted to specifically promote the growth of
      lipophilic yeasts and simultaneously avoid the luxurious growth of other fungi
      and bacteria. With this medium, the conventional bacteriological procedures such
      as microbial streaking for pure culture and anti-microbial sensitivity testing
      could be carried out for these lipophilic yeasts.

PMID- 17191393
TI  - Diagnosis of legionnaires' disease by urinary antigen and DNA detection: a case
      report.
AB  - A 38-year-old male patient who was admitted to a private hospital in Kuala Lumpur
      presented with fever, symptoms of respiratory infection and diarrhoea. On
      admission, he was febrile, toxic looking, dehydrated with hypotension and
      tachycardia. No clinical signs of respiratory infection were detected on
      admission. Initially he was treated as a case of septicaemia with fluid therapy
      and intravenous antibiotic (Perfloxacin). Subsequently, he was noticed to have
      pneumonia in the right lower zone of the lung. His sputum, stool and blood were
      sent for culture and the results were negative. Sputum culture for Legionella and
      serological tests for Mycoplasma and Legionella were also reported negative.
      Sandwich ELISA performed on his urine sample detected Legionella pneumophila
      antigen. L. pneumophila mip gene was also detected in his urine by polymerase
      chain reaction. The patient was commenced on Erythromycin and he responded
      favourably to the treatment. The present case shows that L. pneumophila should
      not be overlooked as one of the causative agents of pneumonia and rapid
      techniques of urinary antigen and DNA detection should be utilized to make an
      early diagnosis of the infection.

PMID- 17191394
TI  - Primary localised deep cutaneous amyloidosis of the eyelid.
AB  - A 62-year-old lady presented with a six-month history of swelling of the left
      upper eyelid, resulting in mild mechanical ptosis. Clinical assessment suggested
      a provisional diagnosis of dermoid cyst. The lesion was excised and histology
      revealed nodular deposits of amorphous eosinophilic material surrounded by
      lymphocytes and plasma cells. Special histochemistry and immunoperoxidase stain
      results showed deposition of amyloid, non-AA type. The lesion recurred 6 months
      later.

PMID- 17191395
TI  - Metastatic mucinous carcinoma of the eyelid.
AB  - Metastatic eyelid tumours are rare and account for less than 2% of all eyelid
      neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60
      year-old Chinese lady presenting with a 2-year history of enlarging, painless
      nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally
      diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous
      carcinoma expressing oestrogen receptor protein. She had a past history of
      mastectomy one year previously and histology showed an infiltrating ductal
      carcinoma (oestrogen receptor status negative) without evidence of axillary lymph
      node metastasis. She had completed adjuvant radio- and chemotherapy. Further
      treatment of the current lesion involved a wide excision which did not show any
      residual malignancy. She had no other evidence of metastasis and was treated with
      letrozol. We highlight this case to create awareness among clinicians and
      opthalmologists on the possibility of metastatic disease as a cause of eyelid
      swelling, especially in patients with a history of cancer. It may also be the
      first sign of metastatic disease of an internal malignancy. A review of the
      literature is also presented.

PMID- 17191396
TI  - Heterotopic ossification in skeletal muscle metastasis from colonic
      adenocarcinoma--a case report.
AB  - Colonic adenocarcinoma metastasising to the skeletal muscle is rare. A-56-yr-old
      Malay man was diagnosed to have adenocarcinoma of the right colon [Dukes B] for
      which a right hemicolectomy was performed, followed by radiotherapy and
      chemotherapy. Five years later the patient presented with a mass in the rectus
      abdominis muscle. The serum carcinoembryonic antigen was 71 ng/Ml. The mass was
      resected. Gross and microscopical examination showed multiple deposits of mucin
      secreting adenocarcinoma with prominent heterotopic ossification in the stroma.
      The exact pathogenesis and significance of heterotopic ossification is not clear,
      but bone morphogenetic proteins may play an important role.

PMID- 17191397
TI  - Negative cross-reactivity of rabbit anti-Malassezia furfur antibodies with other
      yeasts.
AB  - Anti-Malassezia furfur monospecific polyclonal antibodies was produced by
      repeated immunization of rabbit with Malassezia furfur yeast cells mixed with
      Freud adjuvant. The antibody titres of respective rabbit's serum samples prior to
      and after each immunization against M. furfur were assayed by indirect
      immunofluorescence technique using the M. furfur whole yeast antigen fixed in
      Teflon coated slides. The highest anti-M. furfur antibody titre achieved was 1 in
      1280 dilution. At 1:20 dilution, none of the respective serum samples taken at
      various stages of immunization gave positive immunofluorescent staining against
      any of the other species of yeasts tested in this study. Anti-M. furfur
      monospecific polyclonal antibodies produced in rabbit in this study has the
      potential for diagnostic application in immunohistochemical detection of M.
      furfur in human tissues.

PMID- 17191398
TI  - Some variations of case-based techniques for the teaching of undergraduate
      pathology.
AB  - The challenges to the teaching of undergraduate pathology include adapting to the
      ever-evolving medical curriculum and the emergence of new teaching technologies.
      Nevertheless, pathology remains the crucial bridging medical discipline, with the
      pathology teacher playing an important role in consolidating the basic medical
      sciences and leading in the clinical disciplines. In this report, variations of
      case-based teaching of undergraduate pathology are discussed. These can be used
      in pathology lectures, tutorials and practical sessions, both traditional and
      computer-based. They contribute to the pathology teacher's repertoire of teaching
      tools and help add relevance and zest during class.

PMID- 17191399
TI  - Training in community medicine.

PMID- 17191400
TI  - Dr B.C. Dasgupta Memorial Oration. Green revolution & after : the public health
      perspective.

PMID- 17191401
TI  - Dr. K.N. Rao Memorial Oration. HIV epidemic in India and the national response.

PMID- 17191402
TI  - Dr. A.L. Saha Memorial Oration. National rural health mission: an opportunity to
      bridge the chasm between prescription, practice & perception of medical education
      in India.

PMID- 17191403
TI  - P.C. Sen Best Paper Award (2002). Profile of care providers in five blocks of
      Nasik Maharashtra. A window on rural health services in Maharashtra.
AB  - Five blocks of Nasik district in Maharashtra were surveyed in 1999-2000 for
      distribution and academic degrees of doctors of all kinds. The five blocks have
      84 % villages without any health care provider (read doctor) no matter qualified
      or quack. All the 555 doctors including Govt. doctors are concentrated in 16 % of
      villages, mainly in small townships and market centers. Physical access to any
      doctor is thus tedious. Often it requires travelling and hidden costs like loss
      of wages for the accompanying person. It also involves a hidden cost of deferred
      treatment. To ensure access to rational medical care at affordable cost a major
      overhaul of the existing health services is necessary.

PMID- 17191404
TI  - Maternal mortality in seven districts of Uttar Pradesh--an ICMR task force study.
AB  - Maternal mortality is a major health and development concern. The available
      information on maternal mortality in rural India is inadequate and scanty. This
      study presented maternal mortality data from the demographically and
      developmentally (including for health) poor performing state of Uttar Pradesh. A
      descriptive, cross-sectional survey was conducted utilizing a stratified cluster
      sampling design between 1989-90 in eight districts of Uttar Pradesh. Four good
      performing districts namely, Agra, Farrukhabad, Ghaziabad and Badaun from the
      western region and four poor performing districts from the eastern region namely,
      Gorakhpur, Basti, Varanasi and Pratapgarh were chosen. A door-to-door household
      interview survey was carried out in the selected villages covering a population
      of 11.67 lakhs in 889 villages. Maternal mortality rates during 1989 ranged
      between 533745 per 100,000 live births except in Ghaziabad district where the
      rate was as low as 101 per 100,000 live births. The rate in Eastern U.P. was
      higher (573 per 100,000 live births) as compared to that in Western U.P. (472 per
      100,000 live births). A total of 286 maternal deaths were reported during the
      study period. The direct obstetric causes accounted for 55.7% of maternal deaths
      with haemorrhage (26.4%) being the most prevalent. Anaemia and jaundice (17.4%)
      were the most prevalent indirect causes of maternal deaths. Most of the maternal
      deaths could have been prevented if timely medical care was available.

PMID- 17191406
TI  - Knowledge, attitude and practices about zoonoses with reference to
      Campylobacteriosis in a rural area of West Bengal.
AB  - Campylobacteriosis is a leading cause of zoonotic diarrhoea in the developed as
      well as developing countries. Domestic animals particularly the poultry act as a
      source of human infections. Domestic animal rearing is a very common practice in
      India particularly in rural areas. The present study of KAP of Zoonosis showed
      68.2 % of 500 families interviewed did not have knowledge about zoonotic diseases
      in rural Bengal and not a single family had any idea of Campylobacter infections.

PMID- 17191405
TI  - Variations in fat and fatty acid intakes of adult males from three regions of
      India.
AB  - Fat and fatty acid intakes of 25 healthy adult urban males from Ghaziabad, U.P.;
      Goa and Kolkata, W.Bengal, respectively were studied. Fat intakes were estimated
      using dietary records, food frequency questionnaires and chemical analysis of the
      diets consumed. Fatty acid intakes were estimated by gas chromatography. Total
      fat intakes ranged from 26.9 g/day to 163.2g/ day. Percent subjects having
      intakes above the desirable level were 72% in Kolkata, 36% in Ghaziabad, U.P. and
      only 10% in Goa. Visible fat constituted more than 60 percent of total fat. In
      all 3 areas, SFA intakes were higher and MUFA lower than desirable levels.
      Palmitic acid constituted at least 50% of SFA intakes. In Goa, lauric acid, in
      Ghaziabad and Kolkata, stearic acid and myristic acid were major dietary SFAs, In
      Kolkata, erucic acid was 17.3+/-8.3%. Overall 60% of subjects had n-6:n-3 intakes
      close to the desirable ratio. Linoleic acid constituted almost the entire n-6
      intake. Alpha linolenic acid constituted most of the n-3 intakes in Ghaziabad,
      U.P. and Kolkata. The ratios of SFA:MUFA--PUFA vaned widely and percent subjects
      with intakes close to the desirable ratios were 12% in Goa, 23% in Ghaziabad and
      40% in Kolkata. The data highlights the need for limiting fat intakes and
      modifying diets to provide fatty acids in desirable ratios.

PMID- 17191407
TI  - Deciphering the story of Bacillus Calmette Guerin (BCG) vaccine in prevention of
      leprosy.

PMID- 17191408
TI  - Smokeless tobacco use and its implications in WHO South East Asia Region.

PMID- 17191409
TI  - Linking Global Youth Tobacco Survey (GYTS) data to the WHO framework convention
      on tobacco control: the case for India.
AB  - India ratified the WHO Framework Convention on Tobacco Control (WHO FCTC) on
      February 27, 2005. The WHO FCTC is the world's first public health treaty that
      aims to promote and protect public health and reduce the devastating health and
      economic impacts of tobacco. Post ratification, each member state as part of
      general obligation has agreed to develop, implement, periodically update and
      review comprehensive multisectoral national tobacco control strategies, plans and
      programmes in accordance with this Convention and the protocols to which it is a
      Party. The Global Youth Tobacco Survey (GYTS) was developed to track tobacco use
      among young people across countries and the GYTS surveillance system intends to
      enhance the capacity of countries to design, implement, and evaluate tobacco
      control and prevention programs. The South-East Asia Region of WHO has developed
      the "Regional Strategy for Utilization of the GYTS" to meet this need for
      countries in the Region. In 2003, India has passed its national tobacco control
      legislation (India Tobacco Control Act [ITCA]), which includes provisions
      designed to reduce tobacco consumption and protect citizens from exposure to
      second hand smoke. Data in the GYTS (India) report can be used as a baseline
      measure for future evaluation of the tobacco control programs implemented by the
      Ministry of Health and Family Welfare, Government of India. India has to upscale
      some provisions of its National Law to accommodate all of the requirements of
      FCTC. Using determinants measured by GYTS in India, the government can monitor
      the impact of enforcing various provisions of the ITCA and the progress made in
      achieving the goals of the WHO FCTC and the Regional Strategies. Effective
      enforcement of the provisions of ITCA will show in the receding numbers of
      tobacco use prevalence figures and reduction in the expenditures associated with
      tobacco use in India.

PMID- 17191410
TI  - Validity of verbal autopsy in determining causes of adult deaths.
AB  - A verbal autopsy (VA) questionnaire, which had an open-ended description of the
      deceased's illness followed by a series of close-ended questions on specific
      symptoms and signs, was used by three trained field workers to interview
      relatives of the deceased who had died in a Chandigarh hospital in previous year.
      The sensitivity and specificity of the cause of death assigned by physician from
      the verbal autopsy was calculated against the cause of death derived from the
      hospital records. Of the 262 verbal autopsies, 60% were males and 23% belonged to
      rural area. Specificity of VA cause of death was high (>95%) for all broad cause
      groups except cardiovascular (79%) diseases. Sensitivity was highest for injuries
      (85%) and it was in the range of 60% to 65% for circulatory diseases, neoplasms,
      and infectious diseases. Sensitivity was low (20% to 40%) for respiratory,
      digestive and endocrine diseases. Cause specific proportionate mortality for
      major cause groups by the VA were statistically similar to the causes of deaths
      derived from the hospital records (p>0.05). Therefore, VA can be used for
      determining causes of adult deaths.

PMID- 17191411
TI  - Women with septic abortion: who, how and why? A prospective study from tertiary
      care hospital in India.
AB  - A prospective descriptive interview based hospital study was carried on 47 women
      admitted with septic abortion to evaluate their psychosocial, demographic and
      clinical profile These women were predominantly parous (75%), hindus (60%),
      between 20-30 years of age (60%) and mostly married (91.4%) house wives (63.8%).
      More than 90% already had one or more male child. The contraceptive use was
      dismally low (23.4%). Their knowledge about legalisation, place and persons
      authorized to conduct abortions was very less, however large majority (87%)
      underwent abortions within 3 months of pregnancy. Large family, poverty and
      spacing were the main reasons cited for abortions. Abdominal pain, fever, genital
      bleeding, diarhoea and abdominal distension were presenting clinical features in
      order of frequency. Advanced sepsis and associated medical and surgical
      complications were present in more than half the patients and 6% succumbed to
      these problems. The current experience was an eye opener for most of them and
      changed their future attitude. Hence education, economic prosperity, easy access
      to reproductive health facilities and institutional management of sepsis is the
      key to make abortions safe.

PMID- 17191412
TI  - A study of the risk factor profile of cardiovascular diseases in rural Punjabi
      male patients.
AB  - One hundred rural Punjabi males (40-60 years old) admitted to Hero DMC Heart
      Institute, Ludhiana with first cardiac attack were studied to identify major
      determinants of cardiovascular diseases (CVD) among this group. The results
      revealed that 20% and 56% of the subjects were smokers and alcohol takers,
      respectively. Smoking had a significant (p< or =0.01) correlation with serum LDL
      C, triglycerides and systolic blood pressure. 84% had sedentary life style. 36%
      and 7% of the subjects were overweight and obese. The body mass index was
      positively and significantly (p< or =0.01) correlated with serum triglycerides.
      32% and 20% of the subjects had systolic and diastolic blood pressure above
      normal. 22% were diagnosed for hyperglycemia. 6% suffered from
      hypercholesterolemia and 28% had borderline high values of serum cholesterol. 22%
      and 6% had high triglyceride and LDL-C levels, respectively. The study concluded
      that the etiology of CVD is multifactorial and no single factor is an absolute
      cause among the rural Punjabi male patients. Therefore, desirable modification in
      diet and life style can significantly reduce the risk of CVD among rural males of
      Punjab.

PMID- 17191413
TI  - Report of National workshops on National Rural Health Mission.

PMID- 17191414
TI  - Intraoperative magnetic resonance imaging and meningioma surgery.
AB  - OBJECTIVE: To determine if intraoperative magnetic resonance imaging improves
      surgical resection and postoperative outcome of intracranial meningioma. STUDY
      DESIGN: Prospective, non-randomized, cohort study. METHOD: Intraoperative
      Magnetic Resonance Imaging (iMRI) was used to evaluate patients with meningioma
      undergoing surgery. Images were obtained after induction of anaesthesia and at
      various stages of tumour resection. Extent of surgical resection was graded using
      Simpson grading system for meningioma. The images were reviewed together with
      histopathology and early outcome. Primary outcome measure was determined by
      finding unexpected tumur in interdissection images. Secondary outcome measures
      were determined by postoperative complications including infections and
      mortalities. RESULTS: There were 39 procedures in 38 patients from January 1998
      to December 2002. Surgical-planning images helped to optimize craniotomy
      placement. Interdissection images revealed unexpected residual tumour in only 1
      patient. Complete resection (Simpson grades 1-3) was achieved in 33 procedures.
      The average follow up period was 16.4 months. Tumour recurrence has been observed
      in three patients. Two of these patients had anaplastic meningioma. There was no
      mortality in the 30-day postoperative period. CONCLUSION: Intraoperative MRI was
      beneficial in siting the craniotomy in addition to providing anatomical
      relationships between the tumour and adjacent structures in lesions located at
      the skull base though the full benefit of these is yet to be determined. The low
      morbidity and zero mortality recorded in the study may be related to all these
      factors.

PMID- 17191415
TI  - Comparison of Araoye's criteria with standard electrocardiographic criteria for
      diagnosis of left ventricular hypertrophy in Nigerian hypertensives.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is a major risk factor for
      cardiovascular morbidity and mortality. Various electrocardiographic (ECG)
      criteria for LHV give poorer performance in black subjects when compared with
      white subjects. Araoye proposed a code system for improved ECG diagnosis of LVH
      in blacks. The Araoye's criteria are yet to be validated in black subjects. STUDY
      DESIGN: Electrocardiograms and echocardiograms were obtained from 100
      hypertensive subjects and 60 controls. ECG LVH was determined by the Araoye's
      code criteria, Sokolow-Lyon; Cornell voltage; and Romhilt-Estes point score.
      Echocardiographic LVH was defined by LV mass indexed for height at 97.5
      percentile of the controls (126 g.m(-1) and 130 g.m(-1) in females and males
      respectively). RESULTS: The prevalence of echocardiographic LVH indexed for
      height was 34% and 1.67% in the hypertensive and controls respectively while the
      prevalence of electrocardiographic LVH among the hypertensives were 18% by
      Romhilt Estes score, 48% by Sokolow-Lyon's criteria, 22% by Cornell's criteria
      and 51% by Araoye's criteria. The sensitivity and specificity respectively of the
      various electrocardiographic criteria were 65.7% and 76.8% for Sokolow-Lyon,
      25.7% and 88.8% for Cornell's criteria 25.7% and 92.8% for Romhilt-Estes score
      and 71.4% and 74.4% for Araoye's criteria. Araoye's criteria did not differ
      significantly from Sokolow-Lyon criteria in identifying LVH but differed
      significantly from Cornell and Romhilt-Estes criteria. The number of positive
      codes in Araoye's criteria was significantly associated with the blood pressures,
      LV dimensions, and LV mass. CONCLUSION: The Araoye's code system for
      electrocardiographic diagnosis of LVH offer no comparative advantage over Sokolow
      Lyon's criteria. However, the number of positive codes in Araoye's criteria
      identifies those individuals with more severe LVH.

PMID- 17191416
TI  - Transverse thoracic diameter in frontal chest radiographs of an adult Nigerian
      population.
AB  - BACKGROUND: Normal standards for thoracic dimensions that are available in our
      environment are often based on studies conducted on Caucasians. Application of
      such published data to a Nigerian population may lead to erroneous conclusions in
      terms of clinical implication. OBJECTIVE: Our study aimed to establish age and
      sex specific transverse thoracic diameter (TD) for our environment. SUBJECTS AND
      METHODS: The TD of 303 males and females aged between 20 and 93 were obtained in
      a cross sectional study at a tertiary hospital. RESULTS: The mean values for the
      20-39, 40-59 and the 3 60-year-old males were 29.6, 29.0, 27.8 cm respectively.
      The corresponding values for females were 26.3, 27.1 and 25.1 cm. Males had
      significantly larger thoracic diameter than females. The largest mean TD in males
      and females were in the 20-39 and 40-59 age groups respectively. The TD had a
      significant positive correlation with weight, height, body mass index and body
      surface area. The best correlations were with body surface area and weight.
      CONCLUSIONS: Nigerians have a smaller TD than Caucasians. Smaller TD in Nigerians
      is likely to be responsible for their high cardiothoracic ratios in comparison
      with Caucasians or Asians.

PMID- 17191417
TI  - Pattern of some risk factors for cardiovascular disease in untreated Nigerian
      hypertensive patients.
AB  - OBJECTIVE: Coronary heart disease risk factors tend to cluster in patients with
      hypertension. In works done in Nigeria, the hypertensive subjects studied were
      those receiving treatment. Our aim was to evaluate the pattern of these risk
      factors in untreated hypertensive patients. STUDY DESIGN: Fifty untreated
      hypertensives and fifty normotensives were recruited among salary earners in
      Horin, Nigeria, after excluding conditions that can cause dyslipidaemia. Plasma
      total cholesterol (TC), Triglycerides (TG), HDL Cholesterol (HDL-C), LDL
      Cholesterol (LDL-C), Fasting Plasma Glucose (FBG) and Body moras Index (BMI) were
      determined in the subjects. RESULT: Prevalence of hypertension increased with
      age. Plasma TC, HDL-C, LDL-C and BMI were higher in hypertensives (TC; 4.54
      mmol/L +/- 1.56, HDL-C; 1.28 mmol/ L +/- 0.45, LDL-C; 3.21 mmol/L +/- 1.34, BMI;
      26.42 kg/m2 +/- 4.75) than in normotensive controls (TC; 3.20 mmol/L +/- 1.28,
      HDL-C; 0.93 mmol/L +/- 0.41, LDL-C; 2.28 mmol/L +/- 1.01, BMI; 23.37 kg/m2 +/-
      4.75). Overweight was more common in hypertensives (70%) than in normotensives,
      and females constituted 53% of the overweight hypertensives. CONCLUSION: The
      dyslipidaemia associated with hypertension, is here noted to be present before
      commencement of antihypertensive therapy. This observation should influence drug
      prescription for treatment of hypertension. Overweight hypertensives are likely
      to benefit from a concurrent control of blood pressure and body weight

PMID- 17191418
TI  - Oral health status of 12-year-old Nigerian children.
AB  - BACKGROUND STUDY: The World Health Organization has set some goals for the oral
      health of the 12-year olds'. This study, which is being carried out in a
      developing nation, will add to the accumulating data worldwide on this index age
      group. STUDY DESIGN: One thousand six hundred 12-year-old public and private
      secondary school pupils were examined in six local government areas of Lagos
      State. The objective of the study was to assess their oral health status and
      treatment needs. RESULTS: In this study caries prevalence was found to be 24.6%
      with a mean DMFT of 0.46. The "D" component formed the greater proportion
      indicating low dental care in the population. The oral hygiene status (OHIS) of
      the students was generally fair. The girls had better oral hygiene and lower
      prevalence of gingivitis and calculus than the boys. The difference was however
      not significant (p > 0.05). The treatment needs of the students revealed that
      72.7% required periodontal treatment, 34.6% required restorative treatment and
      10.3% required orthodontic treatment. CONCLUSION: This study concludes that even
      though caries level in this age group was low, oral hygiene was fair and the
      utilization of oral health services was poor.

PMID- 17191419
TI  - Immunocytochemistry in the diagnosis of small blue cell tumours of childhood.
AB  - OBJECTIVE: This study attempts to define a limited, cost effective, reliable
      primary panel of antibodies for immunohistology, as an adjunct to morphological
      features, for the diagnosis of Small Blue Cell Tumors (SBCT) which would be
      convenient for use in low resource settings to improve their diagnostic accuracy.
      The choice of antibodies is based on the common childhood tumors in Ibadan and
      limited by financial constraints and availability of antibodies. MATERIALS &
      METHODS: Twenty-five representative cases of previously diagnosed small blue cell
      tumours of childhood were selected from the file of the Department of Pathology,
      University College Hospital, Ibadan. The retrieved blocks were cut and stained
      with antibodies to desmin, leucocyte common antigen, cytokeratin, chromogranin,
      neuron-specific-enolase, vimentin and neurofilament using the avidin-biotin
      technique as previously described. RESULTS: Of the 25 cases studied 24 (96%) gave
      interpretable immunostaining reaction and the immunophenotype of these were
      defined. The staining quality equaled that produced on the control well-fixed
      positive control sections. The final diagnosis of six of the 25 cases changed
      based on immunostaining. Four cases previously diagnosed as lymphoma were
      confirmed to be rhabdomyosarcoma (3 cases) and neuroblastoma, one case each of
      rhabdomyosarcoma and neuroblastoma were both reclassified as lymphoma.
      CONCLUSION: Based on our findings, the use of a small first-line panel of
      antibodies to leucocyte common antigen, desmin and neuron-specific-enolase are
      ideal for immunohistochemical discrimination of SBCT, as an adjunct to
      morphology, in low-resource settings.

PMID- 17191420
TI  - Perforated gastric and duodenal ulcers in an urban African population.
AB  - BACKGROUND: Perforations of the stomach and duodenum are frequent causes of acute
      generalized peritonitis in our environment. This is a prospective study of 331
      cases of gastric and duodenal perforations. STUDY DESIGN: A consecutive series of
      adult patients admitted and treated for acute generalized peritonitis due to
      peptic ulcer perforations was studied prospectively from January 1998 to June
      2004. A specially designed proforma was used to record patient characteristics,
      clinical and operative findings and outcome. Additional information on self
      medication and other relevant social habits was obtained and recorded. The data
      was analysed and the ratio of gastric to duodenal perforations as well as factors
      associated with perforations determined. RESULTS: More males were affected by a
      ratio of 3.3:1. For all the patients the median age was 55.0 and the mean age was
      52.2 +/- 17.5 years. The mean age of the perforated gastric ulcer patients was
      47.7 +/- 17.1 years but higher for perforated duodenal ulcer patients at 64.8 +/-
      11.4 years. There were 244 gastric and 87 duodenal perforations giving a ratio of
      2.8:1. Most of these perforations were associated with the intake of Non
      Steroidal Anti Inflammatory Drugs (NSAIDS) 158 (47.7%), habitual ingestion of
      herbal medicines or concoctions 81 (24.5%) and prolonged fasting for religious
      reasons, 18 (5.4%). Acute renal failure 32 patients (31.1%), continuing or
      persistent peritonitis 12 patients (11.6%), wound infection 25 patients (24.3%),
      and chest infection 12 patients (11.6%), were some of the 103 post-operative
      complications seen. The overall mortality was 73( 22.1%). The death rate from
      perforated duodenal ulcer was 27 (32.2%) and that from perforated gastric ulcer
      was 46 (20.1%). CONCLUSION: In our community perforated gastric ulcer is seen
      more often than perforated duodenal ulcer. These gastric perforations are related
      to the widespread use of NSAIDS and herbal medicines.

PMID- 17191421
TI  - Comparison of the clock test and a questionnaire-based test for screening for
      cognitive impairment in Nigerians.
AB  - BACKGROUND: Since it is projected that by 2020 seventy percent of the elderly
      will reside in developing countries, a reliable screening method for dementia and
      cognitive impairment in general in populations with diverse languages, culture,
      education and literacy will be needed. We sought to determine if the Clock Test,
      a screening test for dementia, was suitable for use in a Nigerian population.
      STUDY DESIGN: Cross-sectional survey of 54 men and 12 women from Northern
      Nigeria. Researchers administered two dementia screening tools: a questionnaire
      based test adapted for use in a Nigerian population and the Clock Test. RESULTS:
      Overall, 53.0% of the subjects had an abnormal Clock Test whereas 10.6% of the
      subjects had an abnormal questionnaire score. Only 9.1% of the subjects had
      abnormal scores on both tests. Subjects with more schooling had a greater
      probability of having a positive clock concept (understanding that a circle
      represented a clock). Of those with more than 6 years of schooling, 91.0% had a
      positive clock concept. Subjects with a negative clock concept were more likely
      to have an abnormal Clock Test (93.3%) than a questionnaire (26.6%). CONCLUSIONS:
      The main finding of our study was the discrepancy between the results of the
      Clock Test and the questionnaire. Performance on the Clock Test appeared to have
      been heavily influenced by education level, indicating the test is not
      universally applicable across cultures. The questionnaire-based test appears to
      reduce the effects of illiteracy on assessing dementia in a Nigerian population.
      Larger studies should be done to control for how education affects the assessment
      of dementia.

PMID- 17191422
TI  - Bacteriology of chronic discharging ears in Port Harcourt, Nigeria.
AB  - OBJECTIVE: The objective of the study was to isolate and identify aerobic
      bacteria in chronic discharging ears and determine their antibiotic
      susceptibilities, which is essential for reasonable empiric treatment. METHODS:
      Ear swabs of discharging ears aseptically collected from 102 patients of various
      age groups attending Ear, Nose, and Throat out-patient clinic at University of
      Port Harcourt Teaching Hospital were cultured for bacterial agents using blood
      agar, chocolate agar and MacConkey agar. Culture plates were incubated
      aerobically at 37 degrees C for 24-48 hours. Isolates were identified using
      standard microbiological methods. Members of the family enterobacteriaceae were
      identified using enterotubes. Antibiotic susceptibility test was carried out for
      13 drugs using disc diffusion method. RESULTS: Seventy-eight percent of the
      patients studied were in the age group 0-14 years and there were more male
      infants than females. Gram negative bacteria comprised 75% of the isolates.
      Predominant isolates were Pseudomonas aeruginosa (41%), Proteus sp. (22%),
      Staphylococcus aureus (22%), Escherichia coli and other coliforms (11%). Drug
      susceptibility profile of the isolates showed that ceftazidime, ceftriazone and
      gentamycin were most effective drugs in vitro. CONCLUSION: The predominant
      bacterial agents in chronic discharging ears in Port Harcourt, Nigeria were gram
      negative bacteria and included Pseudomonas aeruginosa, Proteus sp., Escherichia
      coli. Gram positive bacterial constituted 25 percent of the isolates and included
      Staphylococcus aureus, Staphylococcus epidermidis and streptococcus sp.
      Ceftazidime, ceftrixone and gentamycin were the most effective drugs in vitro.

PMID- 17191424
TI  - Haemorheological parameters of umbilical cord blood of Nigerian newborns:
      correlations with maternal parameters.
AB  - BACKGROUND: Published reports of haemorheological values of umbilical cord blood
      in Nigerian newborns are relatively scanty. The present study therefore aimed to
      determine the values of some basic haemorheological parameters in the umbilical
      cord blood of Nigerian neonates and in the venous blood of their respective
      mothers. The study also aimed to determine if any significant differences or
      correlations exist in these haemorheological parameters between maternal and
      umbilical cord blood. DESIGN: Cross sectional prospective study involving 60
      subjects consisting of 30 newborn neonates and their respective mothers. METHODS:
      The values of haematocrit, erythrocyte sedimentation rate, haemoglobin
      concentration, red blood cell count, white blood cell count, whole blood relative
      viscosity, relative plasma viscosity, fibrinogen concentration, mean corpuscular
      volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin
      concentration were determined in the umbilical cord blood of Nigeria neonates and
      in the respective mothers at the time of birth. RESULTS: Significantly higher
      values of haematocrit, haemoglobin concentration, red blood cell count, whole
      blood relative viscosity and relative plasma viscosity and significantly lower
      values of erythrocyte sedimentation rates were found in umbilical cord blood
      compared to maternal blood (p < 0.05). Significant positive correlations were
      found only in the values of erythrocyte sedimentation rate (ESR), haemoglobin
      concentration, white blood cell count, whole blood relative viscosity and
      relative plasma viscosity between maternal and umbilical cord blood (p < 0.05).
      Both mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration
      showed a negative but non-significant correlation between maternal and umbilical
      cord blood (p > 0.05). CONCLUSION: The present study reports values of basic
      haemorheological parameters in maternal and umbilical cord blood of newborn
      Nigerian neonates and reports significant differences and correlations in these
      parameters between the two groups. This we hope would provide information on
      umbilical cord haemorheology for Nigerian neonatologist since up to the present
      time similar studies have been scanty.

PMID- 17191423
TI  - Can physique and gluteal size predict penile length in adult Nigerian men?
AB  - BACKGROUND: In Nigeria, especially among the Igbo tribe, there is a well-held
      belief that a man's penile size can be predicted from his physique and the size
      of his buttocks, with people of small physique and flat buttocks likely to have
      long penile lengths. STUDY DESIGN: A prospective study to test the scientific
      veracity of this traditional and apparently mythical belief. Stretched penile
      length was measured in 115 men between the ages of 30-65 years and its
      correlation with the body-mass index and the circumference of the hip as measured
      around the most prominent points on their buttocks, was statistically determined.
      RESULT: The mean age of the subjects was 42.30 years (SD = 9.67), with a median
      of 40 years and a range of 30-65 years. The mean penile length was 13.37 cm with
      a median of 13 cm and a range of 7.5-19.5 cm. The mean circumference of the body
      around the buttocks was 96.46 cm (SD = 10.91), median 98 cm, and range 73-122 cm.
      The body-mass index ranged 17.34-44.44, with the mean at 26.87 (SD = 5.86), and
      the median 25.53. Linear regression statistics showed no statistically
      significant correlation between stretched penile length and body-mass index, thus
      physique. There was a significant direct correlation between penile length and
      gluteal size. CONCLUSION: The supposed relationship between penile length and
      gluteal size may have a scientific basis, but contrary to belief, large buttocks
      is more predictive of longer penile length than small buttocks. Penile length has
      no relationship to physique.

PMID- 17191425
TI  - Relationship between sonographic renal length and renal parenchymal thickness in
      normal adult southeast Nigerians.
AB  - AIM: To determine the relationship between sonographic renal parenchymal
      thickness (RPT) and renal length (RL) in normal adult Nigerian. STUDY DESIGN: The
      RL and RPT of 309 normal subjects within the age range of 18-80 years were
      measured sonographically and prospectively. Correlation was performed between RL
      values and RPT usingPearson Linear 'r' test RESULTS: The range of RL value were
      8.5-12.9 cm and the corresponding mean were 10.33 +/- 0.7 cm and 10.45 +/- 0.63
      cm for the right and left kidneys respectively. The range of values for the RPT
      was 1.40-2.4 and the corresponding mean values were 1.91 +/- 0.20 cm and 1.95 +/-
      0.19 cm for the right and left kidneys respectively. There was a strong positive
      correlation between RPT and RL (r = 0.72 and 0.77 for the right and left kidney
      respectively. However for RL values above 11.0 cm the RPT values fluctuated.
      CONCLUSION: From this study, for RL above 11.0 cm there was no relationship with
      RPT. The study suggests that for our population groups, kidneys with RL lower
      than 8.5 cm and RPT of 1.40 cm or less should not be biopsied in contrast to
      webb's criteria.

PMID- 17191426
TI  - A four-year analysis of manuscripts submitted for publication in West African
      Journal of Medicine (June 2001 to May 2005) (a brief report).
AB  - There are various criteria that could be used to rate a tertiary institution. One
      of these is the productivity of the members of staff which is shown by the
      research conducted, publications submitted and manuscripts published in indexed
      journals. Manuscripts submitted and published in one of the highly rated
      indexedjournals in our locality were analysed with a view to identifying how the
      institutions add to knowledge by their contributions. Our findings show that the
      four top-rated institutions in terms of manuscripts published in West African
      Journal of Medicine (WAJM) are University College Hospital (UCH), lbadan,
      University of Ilorin Teaching Hospital (UITH), Obafemi Awolowo University
      Teaching Hospital (OAUTH), and Jos University Teaching Hospital (JUTH).

PMID- 17191427
TI  - Foreign body ingestions in a schizophrenic patient.
AB  - The topic of foreign body ingestion has received extensive coverage in the areas
      of surgery, emergency medicine and pediatrics. A subset of this topic, the
      intentional ingestion of foreign bodies, however, is much less common, and
      involves subtleties in evaluation and management not usually seen in accidental
      ingestions. Here, we report a case of ingestion of a rolled, metal tuna can lid
      in a male prison inmate previously diagnosed with depression and paranoid
      schizophrenia. Following evaluation by the surgical team, the foreign body was
      removed by laparotomy and the patient was discharged back to the prison without
      complication. In many cases, ingestions ofthis type involve a command
      hallucination ordering the patient to swallow the foreign body. Interestingly,
      the patient in the present case reported auditory hallucinations commanding him
      not to swallow the can lid.

PMID- 17191428
TI  - Usefulness of multi-detector row computed tomography for accurate preoperative
      assessment of pancreatic adenocarcinoma: report of a case.
AB  - A 74-year-old female underwent surgical treatment for adenocarcinoma of the
      pancreatic head. Preoperative multi-detector row computed tomography (MD-CT)
      demonstrated tumor invasion into the accessory right colic vein and the branch of
      the middle colic artery (MCA), which was not detected by digital subtraction
      angiography. MD-CT showed anatomical variants in the left hepatic artery arising
      from the left gastric artery, and the right posterior hepatic artery arising from
      the superior mesenteric artery. Three-dimensional reconstruction CT generated a
      clear picture of the anatomy of the region concerned, which is essential for a
      safe operation. The MD-CT findings were highly consistent with the intraoperative
      findings. We have demonstrated that MD-CT is an important and highly accurate
      modality for pancreatic surgery.

PMID- 17191429
TI  - Intrauterine fetal death of one of twins, coexisting with hydranencephaly in the
      surviving co-twin: a case report.
AB  - Hydranencephaly, a relatively rare malformation of the brain, is characterised by
      absence of the cerebral hemispheres and their replacement by sacs filled with
      cerebrospinal fluid. It is one of the recognised forms of intracranial
      malformations associated with intrauterine fetal demise of one of twins in
      monochorionic twin gestation. This report illustrates the development of
      hydranencephaly in a surviving twin sequel to intrauterine fetal demise of the co
      twin.

PMID- 17191430
TI  - Familial polycystic kidney disease in Nigeria: a report of two cases.
AB  - A case of familial polycystic kidney disease is reported. Although isolated cases
      of adult polycystic kidney disease have been reported in our environment, no case
      to our knowledge has been reported with a familial link. Polycystic kidney
      disease is said to be rare in Africans. Although it commonly terminates in
      chronic renal failure, it hardly features in the aetiopathogenesis of end stage
      renal disease requiring some form of renal replacement therapy in African series.
      This, some workers believe may be due to misdiagnosis and under reporting. This
      report is to show that it may not be as rare as suspected, and that the familial
      link shown in the advanced countries is also applicable here. Case 1 was
      diagnosed in the course of evaluation of her clinical disease. Case 2, an aunt of
      Case 1, was diagnosed following investigation of a casual complaint of a painless
      abdominal mass in the wake of her senior brother's death from haemorrhagic
      stroke.

PMID- 17191431
TI  - Cerebral toxoplasmosis in HIV/AIDS: a case report.
AB  - This is a case of HIV infection with cerebral toxoplasmosis. Cerebral
      toxoplasmosis is an AIDS- related infection and is one of the causes of CNS mass
      lesions in AIDS. A 36-year-old male was admitted at Komfo Anokye Teaching
      Hospital (KATH) for a week. He had focal seizures for which he was treated as an
      "epileptic" with herbal preparations. A computerized tomography (CT) head scan
      revealed the characteristic scan findings in CNS toxoplasmosis.

PMID- 17191432
TI  - Latrogenic burns injury complicating neonatal resuscitation.
AB  - A case ofiatrogenic thermal injury in a newborn infant during resuscitation for
      perinatal asphyxia at a secondary health facility is described. The injury, with
      surface area coverage of about 4%, involved the lower limbs. This report
      highlights the poor newborn resuscitation skills of traditional medical practice.

PMID- 17191433
TI  - Acute bilateral anterior shoulder dislocation following domestic assault--case
      report.
AB  - A rare case of acute bilateral anterior shoulder dislocation in an elderly woman
      is presented. This injury resulted from domestic physical assault by her daughter
      inlaw. Patient defaulted after initial treatment--a common practice by patients
      in our society. This case is being reported to highlight the occurrence of this
      rare orthopaedic emergency.

PMID- 17191434
TI  - Perceived changes in well-being: the role of chronological age, target age, and
      type of measure.
AB  - The goal of this study is to investigate whether perceived changes in one's well
      being from the present to the future are related to chronological age, target
      age, and type of measure (psychological well-being versus life satisfaction).
      Young adults (N=114) rated their current well-being and their future well-being
      at one of three target ages (30, 50, or 70 years old) and middle-aged adults
      (N=51) rated their current well-being and future well-being at the target age of
      70 years old. Future self-enhancement effects were observed on both measures of
      well-being for young adults and on life satisfaction for middle-aged adults.
      Future self-enhancement effects were greater for life satisfaction than for
      psychological well-being. One-way MANOVAs showed that there were chronological
      age differences but not target age differences in the magnitude of future self
      enhancement effects for well-being. Future self-enhancement effects were larger
      for young adults than for middle-aged adults.

PMID- 17191435
TI  - The portrayal of older people in television advertisements: a cross-cultural
      content analysis of the United States and South Korea.
AB  - A cross-cultural content analysis of 2295 prime-time television ads--859 ads from
      the United States and 1436 ads from South Korea-was conducted to examine the
      differences in the portrayal of older people between U.S. and Korean ads. In two
      countries, the underrepresentation of older people in ads was found in terms of
      proportions of the actual population. The findings also showed that older people
      are more likely to play major roles in Korean television ads than in U.S. ads. In
      terms of the attributes of older people depicted in ads, differences between U.S.
      and Korean ads were also found. The results showed that Korean television ads are
      likely to more positively depict older people than American television ads are.
      These findings supported the basic assumption of cross-cultural advertising, in
      which the differences in cultural values between the two cultures are related to
      the differences in the contents of their advertisements. However, the problems of
      underrepresentation and stereotypes in the portrayal of older people were still
      identified both in Korean and U.S. prime-time television ads.

PMID- 17191436
TI  - Depressive symptoms among older residents in assisted living facilities.
AB  - Responding to the dramatic growth in Assisted Living Facilities (ALFs), the
      present study focused on mental health among older residents in ALFs. We assessed
      the effects of physical health constraints (chronic conditions, functional
      disability, and self-rated health) and psychosocial resources (social network,
      sense of mastery, religiosity, and attitude toward aging) on depressive symptoms.
      A sample of 150 residents (Mage = 82.8, SD = 9.41) from 17 facilities in Florida
      was used for analyses. Higher levels of depressive symptoms were observed among
      older residents with a greater level of functional disability, poorer self-rated
      health, lower sense of mastery, less religiosity, and less positive attitude
      towards aging. In addition, the linkages between physical and mental health were
      modified by psychosocial resources. For older residents with more positive
      beliefs and attitudes (a higher sense of mastery, greater religiosity, and more
      positive attitudes toward aging), the adverse effects of functional disability or
      poorer self-rated health on depressive symptoms were attenuated. The protective
      roles of psychosocial resources against physical health constraints yield
      important implications for designing prevention and intervention strategies for
      the mental health of older populations in ALF settings.

PMID- 17191437
TI  - Knowledge of memory aging in adulthood.
AB  - The Knowledge of Memory Aging Questionnaire (KMAQ) measures laypersons' knowledge
      of memory changes in adulthood for research or educational purposes. Half of the
      questions pertain to normal memory aging and the other half cover pathological
      memory deficits due to non-normative factors, such as adult dementia. In this
      study, we compared memory knowledge in middle age adults (40-59 years), young-old
      adults (60-79 years) and very old adults (80 years and over). These data were
      collected as a part of the Louisiana Healthy Aging Study, a multidisciplinary
      population-based study that examines the determinants of healthy aging in
      adulthood. Results indicated that very old adults performed more poorly overall.
      Follow-up analyses revealed that they endorsed stereotyped views of normal memory
      aging more often than did the other age groups. Analyses of response accuracy by
      gender yielded comparable performance for men and women. Implications for
      research and the design of educational programs are considered.

PMID- 17191438
TI  - The growth of molecular complexity in the Universe.
AB  - A review is presented of the chemistry of the early Universe and the formation of
      the first stars. The critical role of the formation and destruction of molecular
      hydrogen in determining their initial mass is demonstrated. A qualitative account
      is given of the transformation of astrochemistry that occurred in response to the
      introduction into the Universe of metals. The diagnostic value of astrochemistry
      is illustrated by its use to infer the Galactic ionization rate. The chemistry of
      the interstellar medium is contrasted with that of the atmospheres of planets and
      recent studies of giant extrasolar planets are summarised.

PMID- 17191439
TI  - Chemistry and cosmology.
AB  - The simplest elements, hydrogen and helium, offer a remarkably rich chemistry,
      which has controlled crucial features of the early evolution of the universe.
      Theoretical models of the origin of structure (stars, galaxies, clusters of
      galaxies, etc.) now incorporate this chemistry in some detail. In addition to the
      origin of structure, cosmologists are concerned with observational tests of
      competing world models. Primordial chemistry may give rise to some of the
      earliest departures from thermodynamic equilibrium in the universe. These effects
      may be observable as broad-band spectroscopic distortions of the cosmic
      background radiation, which otherwise exhibits a nearly perfect blackbody
      spectrum. The chemical history of the expanding universe is followed through a
      detailed calculation of the evolution of the abundances of H, H+, H-, H2, H2+,
      H3+, and other minor species. It is shown that continuous absorption by the small
      concentration of H- can produce a distortion in the cosmic background spectrum
      with a maximum at a frequency near nu/c = 9 cm-1 (wavelength 1.1 mm). The
      predicted effect lies only a factor of 5 below current limits. Its detection
      would provide an important test of our understanding of the recombination epoch
      of the universe.

PMID- 17191440
TI  - Extragalactic chemistry of molecular gas: lessons from the local universe.
AB  - Observational constraints provided by high resolution and high sensitivity
      observations of external galaxies made in the millimetre and sub-millimetre range
      have started to put on a firm footing the study of the extragalactic chemistry of
      molecular gas. In particular, the availability of multi-species and multi-line
      surveys of nearby galaxies is central to the interpretation of existent and
      forthcoming millimetre observations of the high redshift universe. Probing the
      physical and chemical status of molecular gas in starbursts and active galaxies
      (AGN) requires the use of specific tracers of the relevant energetic phenomena
      that are known to be at play in these galaxies: large-scale shocks, strong UV
      fields, cosmic rays and X-rays. We present below the first results of an ongoing
      survey, allying the IRAM 30 m telescope with the Plateau de Bure interferometer
      (PdBI), devoted to the study of the chemistry of molecular gas in a sample of
      starbursts and AGN of the local universe. These observations highlight the
      existence of a strong chemical differentiation in the molecular disks of
      starbursts and AGN.

PMID- 17191441
TI  - Raman association of H2 in the early universe.
AB  - We investigate the contribution made by Raman scattering to the formation of
      molecular hydrogen in astrophysical environments characteristic of the early
      stages of the evolution of the universe. In the Raman process that we study, a
      photon is scattered by a pair of colliding hydrogen atoms leaving a hydrogen
      molecule that is stabilized by the transfer of kinetic and binding energy to the
      photon. We use a formulation for calculating the photon scattering cross section
      in which an infinite sum of matrix elements over rovibrational levels of dipole
      accessible electronic states is replaced by a single matrix element of a Green's
      function. We evaluate this matrix element by using a discrete variable
      representation.

PMID- 17191442
TI  - Are gas-phase models of interstellar chemistry tenable? The case of methanol.
AB  - We consider the case of methanol production in cold dark clouds, also known as
      quiescent cores, for which recent work shows that a purely gas-phase synthesis is
      unlikely to produce a sufficient amount to explain the observational fractional
      abundance of approximately 10(-9). Moreover, recent experiments appear to confirm
      a previous hypothesis that methanol can be formed on cold grain surfaces by the
      hydrogenation of CO via successive reactions with hydrogen atoms. In this paper
      we consider two ways of including the surface formation of methanol into chemical
      models of cold dark clouds. First, we use a gas-phase model and artificially
      include the surface formation of methanol in the same manner that the formation
      of molecular hydrogen is included. Secondly, we utilize a gas-grain code with a
      new mechanism for desorption following exothermic chemical reactions on grain
      surfaces. The latter method can reproduce the observed fractional abundance of
      gas-phase methanol and many other gas-phase species in the well-studied cold dark
      cloud TMC1-CP but the best fit to the observational data occurs at times
      significantly later than at ages estimated from gas-phase models.

PMID- 17191443
TI  - Observations of chemical differentiation in clumpy molecular clouds.
AB  - We have extensively mapped a sample of dense molecular clouds (L1512, TMC-1C,
      L1262, Per7, L1389, L1251E) in lines of HC3N, CH3OH, SO and C18O. We demonstrate
      that a high degree of chemical differentiation is present in all of the observed
      clouds. We analyse the molecular maps for each cloud, demonstrating a systematic
      chemical differentiation across the sample, which we relate to the evolutionary
      state of the cloud. We relate our observations to the cloud physical, kinematical
      and evolutionary properties, and also compare them to the predictions of simple
      chemical models. The implications of this work for understanding the origin of
      the clumpy structures and chemical differentiation observed in dense clouds are
      discussed.

PMID- 17191444
TI  - Meteorite nanoparticles as models for interstellar grains: synthesis and
      preliminary characterisation.
AB  - Dust particles and their interaction with gases play important roles in star
      formation and in solar nebulae. Appropriate model dust grains are needed for the
      laboratory simulation of gas-grain interactions. Nanoparticles formed from
      carbonaceous meteorites may be particularly suitable, as these particles are
      formed from materials that were formed originally from interstellar/nebula dust.
      Extending our previous studies with grounded meteorite powders, we demonstrate
      here the production of nanoparticles formed from meteorites using the laser
      desorption/controlled condensation method developed in our laboratory. The
      product nanoparticle aggregates have porous, web-like morphologies similar to
      interstellar dust grains, indicating that they can present large specific surface
      areas for gas/grain interactions. In this paper, we present polarisation
      modulation reflection-absorption infrared spectra (PM-RAIRS) of supported thin
      films and compare these spectra with the known silicate bands in the spectra of
      interstellar dust recorded during the ISO mission. We also report an ultrahigh
      vacuum (UHV) temperature programmed desorption (TPD) study of the adsorption of
      CO on the supported nanoparticle films. The latter allow us to estimate the CO
      binding energy on the meteorite nanoparticles as 13.5 +/- 3.0 kJ mol(-1), cf. a
      value of 9.8 +/- 0.2 kJ mol(-1) for CO binding to a water ice substrate. Such
      thermochemical data can be useful for computational modelling of gas-grain
      interactions under the diverse conditions in interstellar clouds and solar
      nebulae.

PMID- 17191445
TI  - Laboratory investigations of the role of the grain surface in astrochemical
      models.
AB  - The rich chemistry often detected in star forming regions is now recognized to be
      a consequence of solid-state astrochemistry and the thermal desorption of its
      products. In recent experimental studies, desorption of a range of ices from a
      gold surface was investigated using temperature programmed desorption (TPD).
      These data were then used in astrochemical models. In this paper we investigate
      the sensitivity of these models to the inclusion of TPD data obtained from
      different surfaces (simulating different dust grains) and different thicknesses
      of the icy mantles. Detailed laboratory TPD studies of the desorption of ices
      from a highly oriented pyrolytic graphite (HOPG) surface have been performed.
      Desorption temperatures and kinetic parameters have been determined directly from
      the TPD data and have been used to determine the expected desorption temperature
      for the ices from grain surfaces. The results of these experiments have been
      incorporated into astrochemical models of high mass star forming regions and have
      then been compared with the results of previous experiments. From this
      comparison, we are able to determine whether the nature and composition of the
      grain surface is important in dictating the chemistry that occurs in star forming
      regions.

PMID- 17191446
TI  - The formation of interstellar molecules via reactions on dust grain surfaces.
AB  - The formation of molecules in interstellar space via reactions on the surface of
      dust grains has been the subject of numerous theoretical studies, since a very
      important reaction, the formation of molecular hydrogen, is thought to occur
      primarily on dust. Beginning with the very first experiments of the formation of
      H2 on a dust grain analogue by Pirronello et al., in 1997, and continuing today,
      it has been possible to study and characterize the processes of molecular
      hydrogen formation on realistic analogues of dust grains with increasing
      sophistication. In our laboratory, we use state-of-the-art surface science
      techniques to come as closely as technically possible to the conditions of
      molecule formation in the ISM. Here, we present the results of studies on the
      mechanisms and rate of formation of molecular hydrogen on dust grain analogues.

PMID- 17191447
TI  - The temperature-dependence of rapid low temperature reactions: experiment,
      understanding and prediction.
AB  - Despite the success of the CRESU (Cinetique de Reaction en Ecoulement
      Supersonique Uniforme) method in measuring rate coefficients for neutral-neutral
      reactions of radicals down close to the very low temperatures prevalent in dense
      interstellar clouds (ISCs), there are still many reactions of potential
      importance in the chemistry of these objects for which there have been no
      measurements of low temperature rate coefficients. One important class of
      reactions is that between atomic and molecular free radicals and unsaturated
      hydrocarbons; that is, alkynes and alkenes. Based on semi-empirical arguments and
      correlations of 'room temperature' rate coefficients, k(298 K), for reactions of
      this type with the difference between the ionisation energy of the alkyne/alkene
      and the electron affinity of the radical, we suggest which reactions between the
      radicals, C(3P), O(3P), N(4S), CH, C2H and CN, and carbon chain molecules (Cn)
      and cyanopolyynes (HC2nCN and NCC2nCN) are likely to be fast at the temperature
      of dense ISCs. These reactions and rate coefficients have been incorporated into
      a purely gas-phase model (osu2005) of ISC chemistry. The results of these
      calculations are presented and discussed.

PMID- 17191448
TI  - Crossed-beam studies on the dynamics of the C + C2H2 interstellar reaction
      leading to linear and cyclic C3H + H and C3 + H2.
AB  - The dynamics of the C + C2H2 reaction has been investigated using two crossed
      molecular beam apparatus of different concepts. Differential cross sections have
      been obtained for the C(3PJ) + C2H2(X1sigmag+) --> l/c-C3H + H(2S1/2) reaction in
      experiments conducted with pulsed supersonic beams and variable beam crossing
      angle configuration at two relative translational energies ET = 0.80 and 3.5 kJ
      mol(-1). H(2S1/2) atoms were detected by time-of-flight mass spectrometry with
      sequential excitation to the 2PJ(o) state using a laser beam tuned at the Lyman
      alpha transition around 121.567 nm and ionisation by a second laser beam at 364.7
      nm. Doppler-Fizeau spectra of the H atoms were recorded with the Lyman-alpha
      laser beam parallel to the relative velocity vector of the reagents. These
      spectra could be fitted using a forward convolution process including two
      contributions. The recoil energy distribution functions of both contributions
      were taken as statistical, with total energies corresponding to a reaction
      exoergicity deltaH0(o) = -11 kJ mol(-1) for the major one, assigned to the c-C3H
      + H path, and -1.5 kJ mol(-1) for the minor one, assigned to the l-C3H + H path.
      The angular distribution was taken as also statistical (uniform) for the minor
      contribution but somewhat backward peaked for the major one. Differential cross
      sections have been obtained for the three energetically allowed and competitive
      C(3PJ) + C2H2(X1sigmag+) --> l/c-C3H + H(2S1/2) and C(3PJ) + C2H2(X1sigmag+) -->
      C3(X1sigmag+) + H2(X1sigmag+) reaction channels in experiments conducted with
      supersonic continuous beams under 45 degrees crossing angle configuration using
      "soft" electron-ionisation mass spectrometry time-of-flight detection at ET = 3.5
      and 18.5 kJ mol(-1). From measurements of angular and time-of-flight
      distributions at the mass-to-charge ratios m/z = 37 and 36, product angular and
      translational energy distributions have been determined in the centre-of-mass
      system for both linear- and cyclic-C3H isomer formation as well as for C3
      production. The variations of the dynamics and product branching ratios with
      collision energy have been characterized. The ratios c-C3H/l-C3H and C3/C3H from
      the C(3P) reactions have been both found to decrease with increasing ET.
      Formation of C3(X1sigmag+) from the C(3P) reaction has been rationalized in terms
      of intersystem crossing between triplet and singlet C3H2 potential energy
      surfaces. There is good agreement between the results at ET = 3.5 kJ mol(-1)
      obtained with the two different crossed molecular beam techniques for the C(3PJ)
      + C2H2(X1sigmag+) --> l/c-C3H + H(2S1/2) channels. An estimate of the exoergicity
      of the C(3PJ) + C2H2(X1sigmag+) --> c-C3H + H (2S1/2) pathway from the extent of
      the translational energy release corroborates the value of deltaH0(o) = -11 kJ
      mol(-1) obtained from the Doppler-Fizeau measurements. The overall results have
      been discussed in the light of the available theoretical information on the
      relevant triplet and singlet C3H2 potential energy surfaces, and compared with
      the results of previous related kinetic and dynamic work as well as of
      theoretical calculations of the reaction dynamics.

PMID- 17191449
TI  - Dissociative recombination of protonated methanol.
AB  - The branching ratios of the different reaction pathways and the overall rate
      coefficients of the dissociative recombination reactions of CH3OH2+ and CD3OD2+
      have been measured at the CRYRING storage ring located in Stockholm, Sweden.
      Analysis of the data yielded the result that formation of methanol or deuterated
      methanol accounted for only 3 and 6% of the total rate in CH3OH2+ and CD3OD2+,
      respectively. Dissociative recombination of both isotopomeres mainly involves
      fragmentation of the C-O bond, the major process being the three-body break-up
      forming CH3, OH and H (CD3, OD and D). The overall cross sections are best fitted
      by sigma = 1.2 +/- 0.1 x 10(-15) E(-1.15 +/- 0.02) cm2 and sigma = 9.6 +/- 0.9 x
      10(-16) E(-1.20 +/- 0.02) cm2 for CH3OH2+ and CD3OD2+, respectively. From these
      values thermal reaction rate coefficients of k(T) = 8.9 +/- 0.9 x 10(-7) (T/300)(
      0.59 +/- 0.02) cm3 s(-1) (CH3OH2+) and k(T) = 9.1 +/- 0.9 x 10(-7) (T/300)(-0.63
      +/- 0.02) cm3 s(-1) (CD3OD2+) can be calculated. A non-negligible formation of
      interstellar methanol by the previously proposed mechanism via radiative
      association of CH3+ and H2O and subsequent dissociative recombination of the
      resulting CH3OH2+ ion to yield methanol and hydrogen atoms is therefore very
      unlikely.

PMID- 17191450
TI  - Photoprocesses in protoplanetary disks.
AB  - Circumstellar disks are exposed to intense ultraviolet (UV) radiation from the
      young star. In the inner disks, the UV radiation can be enhanced by more than
      seven orders of magnitude compared with the average interstellar radiation field,
      resulting in a physical and chemical structure that resembles that of a dense
      photon-dominated region (PDR). This intense UV field affects the chemistry, the
      vertical structure of the disk, and the gas temperature, especially in the
      surface layers. The parameters which make disks different from more traditional
      PDRs are discussed, including the shape of the UV radiation field, grain growth,
      the absence of PAHs, the gas/dust ratio and the presence of inner holes.
      Illustrative infrared spectra from the Spitzer Space Telescope are shown. New
      photodissociation cross sections for selected species, including simple ions, are
      presented. Also, a summary of cross sections at the Lyman alpha 1216 A line,
      known to be strong for some T Tauri stars, is made. Photodissociation and
      ionization rates are computed for different radiation fields with color
      temperatures ranging from 30000 to 4000 K and grain sizes up to a few microm. The
      importance of a proper treatment of the photoprocesses is illustrated for the
      transitional disk toward HD 141569A which includes grain growth.

PMID- 17191451
TI  - Reaction dynamics of carbon-bearing radicals in circumstellar envelopes of carbon
      stars.
AB  - Crossed molecular beams experiments on dicarbon molecules, C2(X1sigmag+/a3piu),
      with unsaturated hydrocarbons acetylene (C2H2(X1sigmag+), ethylene (C2H4(X1Ag)),
      methylacetylene (CH3CCH(X1A1)), and allene (H2CCCH2 (X1A1)) were carried out at
      18 collision energies between 10.6 and 50.3 kJ mol(-1) utilizing a universal
      crossed beams machine to untangle the reaction dynamics forming hydrogen
      deficient hydrocarbon radicals in circumstellar envelopes of carbons stars and in
      cold molecular clouds. We find that all reactions proceed without the entrance
      barrier through indirect (complex forming) scattering dynamics. Each bimolecular
      collision is initiated by an addition of the dicarbon molecule to the pi bond of
      the unsaturated hydrocarbon molecule yielding initially acyclic (triplet) and
      three- or four-membered cyclic collision complexes (triplet and singlet surface).
      On the singlet surface, the cyclic structures isomerize to form eventually
      diacetylene (HCCCCH; C2/C2H2), butatriene (H2CCCCH2; C2/C2H4), methyldiacetylene
      (CH3CCCCH; C2/CH3CCH), and pentatetraene (H2CCCCCH2; C2/H2CCCH2) intermediates.
      The latter were found to decompose via atomic hydrogen loss yielding the buta-1,3
      diynyl [C4H(X2sigma+) HCCCC], 1-butene-3-yne-2-yl [i-C4H3(X2A') H2CCCCH], penta
      2,4-diynyl-1 [C5H3(X2B1) HCCCCCH2], and penta-1,4-diynyl-3 radical [C5H3(X2B1)
      HCCCHCCH] under single collision conditions. The underlying characteristics of
      these dicarbon versus atomic hydrogen replacement pathways (indirect scattering
      dynamics; no entrance barrier; isomerization barriers below the energy of the
      separated reactants; exoergic reactions) suggest the enormous potential of the
      dicarbon plus unsaturated hydrocarbon reaction class to form highly hydrogen
      deficient carbonaceous molecules in cold molecular clouds and in circumstellar
      envelopes of carbon stars. The studies therefore present an important advancement
      in establishing a comprehensive database of reaction intermediates and products
      involved in bimolecular collisions of dicarbon molecules with unsaturated
      hydrocarbons which can be utilized in refined astrochemical models and also in
      future searches of hitherto unidentified interstellar molecules. Implications of
      these experiments to understand related combustion processes are also addressed.

PMID- 17191453
TI  - Laboratory measurements of the recombination of PAH ions with electrons:
      implications for the PAH charge state in interstellar clouds.
AB  - Laboratory measurements of the recombination of polycyclic aromatic hydrocarbon
      (PAH) ions with electrons are presented. Experimental data have been obtained at
      room temperature for azulene (C10H8) and acenaphthene (C12H10) cations by the
      Flowing Afterglow with PhotoIons method. The results confirm that the
      recombination of PAH ions is fast although well below the geometrical limit. The
      set of our recent and present measurements reveal a definite trend of increasing
      rate with the number of carbon atoms of the PAH. This behaviour that needs
      further characterization is potentially of great interest for charge state models
      as recombination is a dominant mechanism of PAH ion destruction in the
      interstellar medium. The design of experiments to measure the recombination of
      larger PAHs and their temperature dependence is discussed.

PMID- 17191452
TI  - Carbon molecules in space: from astrochemistry to astrobiology.
AB  - How complex carbonaceous molecules in space are, what their abundance is and on
      what timescales they form are crucial questions within cosmochemistry. Despite
      the large heterogeneity of galactic and interstellar regions the organic
      chemistry in the universe seems to follow common pathways. The largest fraction
      of carbon in the universe is incorporated into aromatic molecules (gaseous
      polycyclic aromatic hydrocarbon as well as solid macromolecular aromatic
      structures). Macromolecular carbon constitutes more than half of the interstellar
      carbon, approximately 80% of the carbon in meteorites, and is likely to be
      present in comets. Molecules of high astrobiological relevance such as N
      heterocycles, amino acids and pre-sugars have all been identified in trace
      quantities (ppb) in extracts of carbonaceous meteorites. Their presence in inter-
      and circumstellar regions is either unknown or contentious. In any event such
      fragile species are easily destroyed by UV radiation, shocks and thermal
      processing and are unlikely to survive incorporation into Solar System material
      without some degradation. The more refractory material, in particular
      macromolecular carbon may retain an interstellar heritage more faithfully. We
      present laboratory measurements on the photostability of organic compounds and
      discuss their survival in regions with elevated UV radiation. We also show recent
      observations of diffuse interstellar bands indicating the presence of fullerenes.
      We investigate the link between the carbon chemistry in interstellar space and in
      the Solar System by analyzing the carbonaceous fraction of meteorites and by
      reviewing stable isotopic data. It also seems evident that both volatile and
      refractory material from carbonaceous meteoritic has been substantially altered
      owing to thermal and aqueous processing within the Solar System.

PMID- 17191454
TI  - Structure of vapour deposited adenine on a nanostructured perovskite surface
      studied by STM.
AB  - The structures of vapour deposited layers of adenine on a nanostructured
      SrTiO3(001) surface have been investigated by scanning tunneling microscopy
      (STM). The STM images reveal details of self-organization of adenine monolayers
      in which adsorption is controlled both by substrate nanostructure and by
      intermolecular H-bonding of adenine molecules. Detailed examination of STM images
      suggests that at least three different ordering structures are possible and two
      distinct orientations may exist with opposite chirality.

PMID- 17191455
TI  - VUV spectroscopy and photo-processing of astrochemical ices: an experimental
      study.
AB  - In order to understand much of the chemistry that underpins astronomical
      phenomena (e.g. star and planet formation) it is essential to probe the physico
      chemistry of ice surfaces under astronomical conditions. The physical properties
      and chemical reactivity of such icy surfaces depends upon its morphology. Thus it
      is necessary to explore how the morphology of astrochemical ices is influenced by
      their local environment (e.g. temperature and pressure) and the mechanisms by
      which they are processed. In this paper we report the results of a series of
      experiments to explore the morphology of a variety of molecular ices using VUV
      spectroscopy. Spectral signatures are found that may allow the morphology of such
      ices to be identified.

PMID- 17191456
TI  - Comparative studies of O2 and N2 in pure, mixed and layered CO ices.
AB  - We present laboratory data on pure, layered and mixed CO and O2 ices relevant for
      understanding the absence of gaseous O2 in space. Experiments have been performed
      on interstellar ice analogues under ultra high vacuum conditions by molecular
      deposition at 14 K on a gold surface. A combination of reflection absorption
      infrared spectroscopy (RAIRS) and temperature programmed desorption (TPD) is used
      to derive spectroscopic and thermodynamic properties of the ices. It is found
      that for pure ices the desorption energy of O2 is larger than that of CO and N2.
      TPD spectra reveal similar desorption processes for all examined CO-O2 ice
      morphologies. The different amorphous and crystalline components of pure 13CO
      RAIR spectra are analyzed. The RAIRS data of the 13CO stretching vibration show a
      significant difference between layered and mixed CO-O2 ices: layered CO-O2 ices
      resemble that of pure 13CO whereas the spectra of mixed ices are broadened. The
      experiments also show that the sticking probabilities of O2 on CO and O2 on O2
      are close to unity. These new results are compared with recently analyzed data of
      CO-N2 ices. The differences in the TPD and RAIRS spectra of the CO-N2 and CO-O2
      ice systems are explained by differences in quadrupole intermolecular
      interactions and by different crystallization processes of these ices.

PMID- 17191457
TI  - New trends in cometary chemistry.
AB  - This paper presents some of the implications of new comet observations for
      cometary chemistry: recent observations of bright comets, space missions, and
      especially the first results of the Deep Impact experiment. Topics which are
      discussed are the molecular complexity of cometary material, the evidence for
      molecular diversity from the infrared observations by Deep Impact, possible
      relations between cometary nuclei and carbonaceous chondrites, the sites of ices
      in cometary nuclei, the problem of interpretation of the spin temperatures
      observed in cometary molecules.

PMID- 17191458
TI  - Between heaven and Earth: the exploration of Titan.
AB  - The atmosphere of Titan represents a bridge between the early solar nebula and
      atmospheres like ours. The low abundances of primordial noble gases in Titan's
      atmosphere relative to N2 suggest that the icy planetesimals that formed the
      satellite must have originated at temperatures higher than 75-100 K. Under these
      conditions, N2 would also be very poorly trapped and thus Titan's nitrogen, like
      ours, must have arrived as nitrogen compounds, of which ammonia was likely the
      major component. This temperature constraint also argues against the trapping of
      methane. Production of this gas on the satellite after formation appears
      reasonable based on terrestrial examples of serpentinization, disproportionation
      and reduction of carbon. These processes require rocks, water, suitable catalysts
      and the variety of primordial carbon compounds that were plausibly trapped in
      Titan's ices. Application of this same general scenario to Ganymede, Callisto,
      KBOs and conditions on the very early Earth seems promising.

PMID- 17191459
TI  - Hydrogen cyanide polymers, comets and the origin of life.
AB  - Hydrogen cyanide polymers--heterogeneous solids ranging in colour from yellow to
      orange to brown to black--could be major components of the dark matter observed
      on many bodies of the outer solar system including asteroids, moons, planets and,
      especially, comets. The presence on cometary nuclei of frozen volatiles such as
      methane, ammonia and water subjected to high energy sources makes them attractive
      sites for the ready formation and condensed-phase polymerization of hydrogen
      cyanide. This could account for the dark crust observed on Comet Halley in 1986
      by the Vega and Giotto missions. Dust emanating from its nucleus would arise
      partly from HCN polymers as suggested by the Giotto detection of free hydrogen
      cyanide, CN radicals, solid particles consisting only of H, C and N, or only of
      H, C, N, O, and nitrogen-containing organic compounds. Further evidence for
      cometary HCN polymers could be expected from in situ analysis of the ejected
      material from Comet Tempel 1 after collision with the impactor probe from the two
      stage Deep Impact mission on July 4, 2005. Even more revealing will be actual
      samples of dust collected from the coma of Comet Wild 2 by the Stardust mission,
      due to return to Earth in January 2006 for analyses which we have predicted will
      detect these polymers and related compounds. In situ results have already shown
      that nitriles and polymers of hydrogen cyanide are probable components of the
      cometary dust that struck the Cometary and Interstellar Dust Analyzer of the
      Stardust spacecraft as it approached Comet Wild 2 on January 2, 2004. Preliminary
      evidence (January 2005) obtained by the Huygens probe of the ongoing Cassini
      Huygens mission to Saturn and its satellites indicates the presence of nitrogen
      containing organic compounds in the refractory organic cores of the aerosols that
      give rise to the orange haze high in the atmosphere of Titan, Saturn's largest
      moon. Our continuing investigations suggest that HCN polymers are basically of
      two types: ladder structures with conjugated -C=N- bonds and polyamidines readily
      converted by water to polypeptides. Thermochemolysis GC-MS studies show that
      cleavage products of the polymer include alpha-amino acids, nitrogen heterocycles
      such as purines and pyrimidines, and provide evidence for peptide linkages.
      Hydrogen cyanide polymers are a plausible link between cosmochemistry and the
      origin of informational macromolecules. Implications for prebiotic chemistry are
      profound. Following persistent bolide bombardment, primitive Earth may have been
      covered by water and carbonaceous compounds, particularly HCN polymers which
      would have supplied essential components for establishing protein/nucleic acid
      life.

PMID- 17191460
TI  - Small-scale-structure of the interstellar medium probed through diffuse band
      observations.
AB  - The carriers of the diffuse interstellar band spectrum represent an important
      baryonic component of the interstellar medium (ISM) and it is expected that their
      identification will contribute significantly to the understanding of the
      chemistry and physics of interstellar clouds. It is widely held that the carriers
      are linked to the presence of dust grains on account of the good correlation of
      their strengths with interstellar reddening, so they offer an important potential
      route to improving our understanding of the composition and chemistry of grains
      and grain surfaces. In addition to the challenge of making the spectral
      assignments, an important current question concerns the spatial distribution and
      physical state of interstellar material, with recent observational atomic and
      molecular line absorption studies suggesting that diffuse clouds are more
      'clumpy' than previously thought. We describe here high signal-to-noise optical
      observations made at the Anglo-Australian Telescope using UCLES that were
      undertaken to investigate the spatial distribution of diffuse band carriers. We
      describe the first detection of 'small-scale-structure' in the diffuse band
      carrier distribution in the ISM, and comment on the possibilities that these data
      hold for contributing to the solution of the diffuse band problem and our
      understanding of the nature of small-scale-structure in the diffuse ISM.

PMID- 17191461
TI  - Polycyclic aromatic hydrocarbons, carbon nanoparticles and the diffuse
      interstellar bands.
AB  - Observational data on the appearance and properties of the diffuse interstellar
      bands (DIBs) are reviewed in the context of a model in which the proposed
      carriers of these bands are large carbon molecules and carbon nanoparticles
      containing between 30 and several hundred carbon atoms. The abundance of these
      carriers, as estimated from the observed strengths of the DIBs, place strong
      constraints on their rates of formation and destruction, and suggest that the
      strongest bands, including that at 4428 A, could be produced via the
      decomposition of larger carbon particles, possibly those particles that have been
      postulated to be the source of the 2175 A extinction feature. Such particles are
      of mixed sp2 and sp3 carbon composition, with sizes between that of large
      molecules and small macroscopic solids. Any description of their characteristics
      must combine aspects of molecular and condensed matter physics, and this is
      incorporated in the present discussion. I discuss recent experimental and
      theoretical data related to these matters.

PMID- 17191463
TI  - Role of lysozyme inhbitors in bacterial colonization of egg albumen.

PMID- 17191462
TI  - Proteome and sugar analysis of abiotic stress underlying cryopreservation in
      potato.

PMID- 17191464
TI  - Probabilistic exposure assessment of patulin in apple juice for preschool
      children in flanders.

PMID- 17191465
TI  - Effect of CO2 on the resuscitation of Listeria monocytogenes injured by mild
      inactivation techniques.

PMID- 17191466
TI  - Evaluation of the content and bioactivity of phenolic compounds in olive oil.

PMID- 17191468
TI  - The adoption of soil conservation measures in Belgium. An application of the
      theory of planned behaviour.

PMID- 17191467
TI  - Spatial impact of isolation distances between parcels of GM and non-GM maize.

PMID- 17191469
TI  - Influence of the botanical composition of forages on rumen, milk and tissue fatty
      acid metabolism.

PMID- 17191470
TI  - Metal nanocolloids as innovative pseudohomogeneous catalysts.

PMID- 17191471
TI  - Beta-azidocyclopropanediesters: useful building blocks with potential application
      in agricultural and pharmaceutical chemistry.

PMID- 17191472
TI  - Assessment of flows and sediment loads in a catchment under conflict in
      Sumberjaya, Lampung, Sumatra.

PMID- 17191473
TI  - The quality of exogenous organic matter: influence on earthworm abundance.

PMID- 17191474
TI  - Removal of heavy metals in constructed wetland microcosmos: effects of sorption,
      sulphate reduction and Phragmites australis.

PMID- 17191475
TI  - Continuous electricity generation at high voltages and currents using stacked
      microbial fuel cells.

PMID- 17191476
TI  - No evidence of a plant extinction debt in highly fragmented calcareous grassland
      in Belgium.

PMID- 17191477
TI  - RNA interference (RNAI) as a tool to engineer high nutritional value in chicory
      (Chicorium intybus).
AB  - The major component of chicory (Chicorium intybus) root is inulin, which is a
      polymer of fructose. Inulin production from chicory is hampered by the enzyme
      fructan 1-exohydrolase (1-FEH) that degrades inulin and limits its yield.
      Increased FEH activity results in massive breakdown of fructan and production of
      Fructose and inulo-n-oses. The latter phenomena are to be avoided for industrial
      fructan production. RNA silencing, which is termed post-transcriptional gene
      silencing (PTGS) in plants, is an RNA degradation process through sequence
      specific nucleotide interactions induced by double-stranded RNA. For genetic
      improvement of crop plants, RNAi has advantages over antisense-mediated gene
      silencing and co-suppression, in terms of its efficiency and stability. We are
      generating a transgenic chicory plants with suppressed FEH (exohydrolas) genes
      using RNAi resulting in supressed inulin degradation. A small but important part
      of the construct is a sequence unique for the target gene (exons) or genes,which
      were cloned. The hairpin constructs were made and chicory was transformed by
      Agrobacterium tumifaciense, strain (C58C1). The transgenics should be select and
      check by means of molecular techniques.

PMID- 17191478
TI  - A life-saving food plant producing more neurotoxin under environmental stress.

PMID- 17191479
TI  - Accumulation of biohydrogenation intermediates and changes in the rumen protozoal
      population after micro algae feeding to dairy cattle.

PMID- 17191480
TI  - Searching for bacterial lysozyme inhibitors.

PMID- 17191481
TI  - Seasonal growth dynamics of the moss Omenthypnum nitens in a subarctic heath
      ecosystem.

PMID- 17191482
TI  - Isolation of lytic Pseudomonas aeruginosa bacteriophages from worldwide collected
      water samples.

PMID- 17191483
TI  - Artificial neural networks to model the rumen fermentation pattern in dairy
      cattle.

PMID- 17191484
TI  - Determination of pesticide emission fluxes from canopy using micrometeorological
      methods.

PMID- 17191485
TI  - The efficiency of drift-reducing measures to protect the Flemish environment.

PMID- 17191486
TI  - Modeling the performance of a membrane bioreactor controlled by air sparging.

PMID- 17191487
TI  - Silicon-based hydrophobation agents for wood.

PMID- 17191488
TI  - The influence of 10 years reduced tillage on the potential carbon mineralization
      of silt loam soils under a temperate climate.
AB  - The influence of 10 years reduced tillage (RT) on the potential carbon
      mineralization of the 0-5 cm layer of silt loam soils in Belgium under a
      temperate climate was investigated. Therefore, four fields at three locations
      under 10 years of RT and fields under conventional tillage (CT) with comparable
      crop rotation were selected. The higher % soil organic carbon in the upper layer
      resulted in a higher potential carbon mineralization of the RT fields. The small
      increase in % soil organic carbon and potential carbon mineralization of RT
      fields was contributed to the high soil disturbance due to incorporation of
      manure in the upper layer and the production of sugar beets and potatoes.
      Simulating ploughing by emptying and refilling the soil cores resulted mostly in
      a higher potential carbon mineralization. However, the differences were not
      significant due to the high variability in potential carbon mineralization.

PMID- 17191489
TI  - In vitro polyploidisation in the family of the ranunculaceae.

PMID- 17191490
TI  - Solubility of ozone in polymers: experimental determination.

PMID- 17191491
TI  - Nature knows: heuristic search algorithms optimizing a fuzzy rule-based fish
      habitat suitability model for rivers.

PMID- 17191492
TI  - The use of low-quality water on the transport and transformation of waste water
      in irrigation soils.
AB  - Waste water use for agricultural production in the semi-arid and arid climate
      areas is increasingly regarded as a solution for water shortage. Still today many
      questions remain unanswered about the mid- and long-term effect of irrigation by
      waste water on plant, soil and human health. In this paper the effect of the use
      of waste water on the soil hydraulic properties, the solute transport and
      transformation behaviour is being studied conducting steady state and non-steady
      state waste water application treatments on undisturbed soil columns and a field
      plot. Detailed spatial and temporal information on the propagation of water and
      solute is obtained using tensiometers, soil solute extraction and time domain
      reflectometry probes. The experimental data are processed using the HYDRUS-2D
      modeling tool. After calibration, the model is used in a predictive way as to
      simulate the mid- and long-term effects of the use of treated waste water as
      irrigation water.

PMID- 17191493
TI  - Confocal microscopy confirms the presumed cytoplasmic/nuclear location of plant,
      fish and fungal orthologs of the Galanthus nivalis agglutinin.

PMID- 17191494
TI  - Influence of harvest date on the yield and quality of chicory (Cichorium intybus
      L.).

PMID- 17191495
TI  - Site specific herbicide treatment of weeds in sugar beet crop.

PMID- 17191496
TI  - Prolongation of the shelf-life of minimally processed vegetables by mild
      treatments.

PMID- 17191497
TI  - Arabinoxylan oligosaccharides with different structures exert a bifidogenic
      effect in a mixed intestinal community.

PMID- 17191498
TI  - Reductive dechlorination at high aqueous TCE concentrations.

PMID- 17191499
TI  - Characterization of a key neuropeptide processing enzyme in C. elegans by mass
      spectrometry.

PMID- 17191500
TI  - Early childhood development project in Uganda as a strategy for reducing
      children's poor growth indicators: an explanatory study.
AB  - This study shall explore the activities of the Uganda nutrition and early
      childhood development project using explanatory program effects, qualitative
      research methods to determine the role/interplay of project factors and community
      dynamics in relation to poor growth and social indicators in Ugandan children.
      This project aimed to improve the quality of life for children age less than 6
      years by improving their nutrition, health, cognitive and psychosocial
      development. The key concern remains how successful and sustainable are the
      outcomes? Data shall be collected using interviews, focus groups and document
      reviews. Data analysis shall employ the thematic networks analytical tool, which
      is aided by the ATLAS.ti software. The key hypotheses and recommendations from
      the analysis shall then be tested in a suitable community location and period in
      line with the research questions.

PMID- 17191501
TI  - Implementation and optimisation of the water framework directive explorer for
      river management in Flanders.

PMID- 17191502
TI  - Temperature alters the functional response of the predatory insect Picromerus
      bidens.

PMID- 17191503
TI  - Isolation and characterization of a MADS-box type gene from apple (Malusx
      domestica).

PMID- 17191504
TI  - Influence of turgor on micromechanical properties of apple tissue.

PMID- 17191505
TI  - Development of a variable rate fertilisation system using soil VIS-NIR sensor for
      phosphorus application.

PMID- 17191506
TI  - Modelling fruit microstructure.

PMID- 17191507
TI  - Screening of N-acyl-L-homoserine lactone production by bacteria isolated from
      fresh foods.

PMID- 17191508
TI  - Integrated benchmarking for selection of wastewater treatment technologies in Ho
      Chi Minh City-Vietnam.

PMID- 17191509
TI  - The role of water on the formation of acrylamide in a potato model system.

PMID- 17191510
TI  - Gas-chromatographic method for quantifying carvacrol, thymol, terpinen-4-ol,
      transl anethole, eugenol and trans-cinnamaldehyde in media simulating pig gut
      conditions.

PMID- 17191512
TI  - A novel approach in environmental valuation methods.

PMID- 17191511
TI  - Fermented liquid feed for weaned piglets.

PMID- 17191513
TI  - Decomposition of sugar beet residues from three tillage systems in a temperate
      climate.

PMID- 17191514
TI  - Mobility of nutrients and heavy metals in the sediment of a retention basin for
      combined sewer overflows.

PMID- 17191515
TI  - The solid-solution partitioning of heavy metals (Cd and Zn) in soil and dredged
      sediments for environmental management purposes.

PMID- 17191516
TI  - Effects of common reed (Phragmites spp.) in constructed wetland for removing
      phosphorous and nitrogen from domestic wastewater.

PMID- 17191517
TI  - Riboflavin induces resistance in rice against Rhizoctonia sheath diseases by
      activating signal transduction pathways leading to upregulation of rice cationic
      peroxidase and formation of lignin as a structural barrier.

PMID- 17191518
TI  - Fame-based Bacillus species identification using artificial neural networks.

PMID- 17191519
TI  - Nutritional-toxicological conflict of fish consumption: a tool for combined
      intake assessment.

PMID- 17191520
TI  - Stomatal resistance under drought stress conditions induced by PEG 6000 on wild
      almond.

PMID- 17191521
TI  - A proteomic approach to study flesh browning in stored 'conference' pears.

PMID- 17191522
TI  - Effect of antioxidant supplementation in diets of broilers on the oxidative
      status of plasma.

PMID- 17191524
TI  - Effect of pressure and temperature combination on the stability of (6R,S) 5
      methyl and (6R,S) 5-formyltetrahydrofolic acid in model system.

PMID- 17191523
TI  - Bioassays for insecticidal activity of iris ribosome-inactivating proteins
      expressed in tobacco plants.

PMID- 17191525
TI  - Resistance development of bacterial biofilms against bacteriophage attack.

PMID- 17191526
TI  - Supply chain relationships and satisfaction in the agribusiness sector.

PMID- 17191527
TI  - Effect of components in red clover on plant lipase activity with possible
      consequences on PUFA-content of dairy products.

PMID- 17191528
TI  - Micropropagation of the medicinal plant Maesa lanceolata Forssk.

PMID- 17191529
TI  - Antimicrobial activity of gaseous chlorine dioxide: interference by food
      components.

PMID- 17191530
TI  - Tools for participatory water management: the modeling approach.

PMID- 17191531
TI  - Microbial safety of mayonnaise based salads: a growth/no growth model for
      Listeria monocytogenes as a predictive tool.

PMID- 17191532
TI  - Role of quorum sensing in resistance of Serratia plymuthica against Acanthamoeba
      castellanii.

PMID- 17191533
TI  - Shifting from an illegal-drug policy to a psychoactive substance policy.

PMID- 17191534
TI  - Introducing Health Impact Assessment (HIA) in Switzerland.

PMID- 17191535
TI  - [Using the synergies between strategic environmental evaluation and HIA to
      advance the integration of environmental and health issues in public decision
      making processes].
AB  - The Geneva rule was the first one in Switzerland to introduce the concept of
      Strategic Environmental Assessment (SEA). This assessment constitutes a decision
      making aid which describes the process set up to allow evaluation of potential
      environmental impact and comparison of possible variants, recommends the choice
      for the best option and suggests the precautions to take. It presents much
      resemblances to HIA. In this case therefore the application of SEA in the urban
      planning project MICA has been presented. It is in this framework that a first
      experience of integration HIA to the SEA process was realized. In an additional
      way to SEA, HIA is focused on the following fields of potential impact: transport
      and movements, housing, public facilities, water management.

PMID- 17191536
TI  - Health Impact Assessment: how the Canton of Ticino makes health a common issue.
AB  - HIA is based on the theory of health determinants, which recognizes that well
      being is determined by a wide range of economic, social and environmental
      factors, by heredity and medical intervention. The intended HIA procedure
      represents a new approach to the evaluation of all cantonal policies in order to
      assess their potential health impacts and to improve the quality of governmental
      decisions, through recommendations to enhance predicted positive health impacts
      and minimize negative ones.

PMID- 17191537
TI  - [Health Impact Assessment--yet another new illusion of efficacy or a truly useful
      tool for decision-making?].
AB  - Since 1999, the Canton of Jura has been contributing to international and
      national efforts towards sustainability. In this context, and under strong
      political support, people in this Canton have been engaging upon implementation
      of health impact assessment techniques. This paper describes the main lessons to
      be learned from this local experience.

PMID- 17191538
TI  - A programme for Health Impact Assessment in Brighton and Hove.
AB  - HIA is based on the theory of health determinants, which recognizes that well
      being is determined by a wide range of economic, social and environmental
      factors, by heredity and medical intervention. The intended HIA procedure
      represents a new approach to the evaluation of all local authority policies in
      order to assess their potential health impacts and to improve the quality of
      governmental decisions, through recommendations to enhance predicted positive
      health impacts and minimize negative ones.

PMID- 17191539
TI  - Health impact assessment and advocacy: a challenging combination.

PMID- 17191540
TI  - Monitoring population disability: evaluation of a new Global Activity Limitation
      Indicator (GALI).
AB  - OBJECTIVE: To evaluate a single item instrument, the Global Activity Limitation
      Indicator (GALI), to measure long-standing health related activity limitations,
      against several health indicators: a composite morbidity indicator, instruments
      measuring mental health (SCL-90R, GHQ-12), physical co-morbidity and physical
      limitations (ADLs, SF-36). METHODS: Cross-sectional data (n = 9168) of the 2001
      National Health Interview Survey in Belgium was used to compare the GALI with
      other health indicators across gender, age, educational attainment and language.
      RESULTS: Responses to the GALI were similar to responses to other indicators of
      physical limitations (Limitations in Activities of Daily Living (by severity or
      by number of limitations), the SF-36 physical domain), to an indicator of chronic
      physical comorbidity and to indicators of mental health. The probability of
      reporting absence of long-standing activity limitation with the GALI was high in
      subjects without physical limitations or physical or mental conditions. This
      probability decreased as the severity or number of limitations, the number of
      physical or mental conditions increased. CONCLUSIONS: The GALI performs
      appropriately against other health indicators and appears to reflect long
      standing activity limitation associated with both mental and physical conditions.

PMID- 17191541
TI  - Subjective health complaints, health-related quality of life and physician
      visits: results of the study of health in Pomerania (SHIP).
AB  - OBJECTIVES: To investigate the relationship between subjective health complaints
      (SHCs), health-related quality of life and physician visits. METHOD: 3'773
      participants of the Study of Health in Pomerania (SHIP) filled questionnaires and
      were interviewed. Data consisted of 1) 38 statements concerning SHCs, 2) the
      SF12, and 3) statements concerning visits to 11 different groups of physicians.
      Factor analysis was done on the SHC data, with a subsequent varimax rotation.
      Relationships between resulting factors and remaining variables were analysed
      using 1) the cumulative logit model for the first SF12 item (overall health
      evaluation), 2) linear regression for the physical and mental sum scores of the
      SF12, and 3) logistic regression for physician visits. RESULTS: Eight factors
      have eigenvalues greater than one and together explain 54.2% of total variance.
      Varimax rotated factors can be interpreted easily. Altogether, these factors, sex
      and age significantly affect the first SF12 item (Nagelkerke's R2 = 0.27), both
      sum scores (physical: R2adj. = 0.40; mental: R2adj. = 0.36), and all physician
      visits (Nagelkerke's R2 between 0.03 and 0.23). CONCLUSIONS: Subjective health
      complaints are important. Total sum scores of typical SHC questionnaires do not
      reflect all relevant aspects of SHCs.

PMID- 17191542
TI  - Words of wisdom.

PMID- 17191543
TI  - May I take your order please?

PMID- 17191544
TI  - Building an outpatient imaging center: a case study at Genesis Healthcare System,
      part 1.
AB  - In the first of two parts, this article provides an outline of key steps in
      creating a freestanding diagnostic imaging center (Genesis HealthCare System
      located in Zanesville, OH) and provides details on a few of the significant
      processes. The following are highlighted in this article: Overview, market
      assessment, facility design, and equipment selection. Part 2 will feature
      operational process improvements. The length of the Genesis project extended to
      about 18 months due to the added services of urgent care and a community
      education and meeting facility. The project began in July 2005 and was completed
      in January 2006 (if the project was focused only on imaging, it could have been
      complete in about 8 to 10 months, see Figure 1 for a typical summary work task
      timeline). This multi-service outpatient center, The Genesis Healthplex on Maple,
      was created in an existing facility that was once a large grocery store. A
      significant goal that came out of the project was to create the perfect customer
      experience. The customer is defined as: Patients, patient families, referring
      physicians and their staff, radiologists, and employees. This was achieved by
      bringing the 3 entities of people (patient/family, staff, and physicians) working
      closely together by utilizing well identified processes and employing technology
      that the market demands. Only when these areas overlap and work together will the
      perfect customer experience be created. See Figure 2.

PMID- 17191545
TI  - Reducing medical necessity denials.

PMID- 17191547
TI  - VP 101.

PMID- 17191546
TI  - CR digital mammography: an affordable entry.
AB  - CR full-field digital mammography (FFDM) has been used extensively in other
      countries, and it was one of the 4 digital mammography technologies employed in
      the Digital Mammographic Imaging Screening Trial. Affordability and easy
      integration with pre-existing mammography systems makes CR FFDM an attractive way
      to secure the advantages of filmless mammography imaging. CR mammography is true
      digital mammography--it is merely a different way of acquiring the image. The FDA
      has recently approved the first CR FFDM system for sale in the United States. At
      Gundersen Lutheran Health System (La Crosse, Wisconsin), CR FFDM is the most
      practical technology for realizing the potential everyday clinical benefits of
      filmless mammography imaging.

PMID- 17191548
TI  - PACS site visits: when, where, who, and how.
AB  - Used correctly, site visits will greatly facilitate the decision making process
      and will encourage consensus among the PACS selection team. Further, site visits
      are a great way to see a product in action, to learn from others mistakes and
      successes, and to make some great contacts for your ongoing PACS journey. Being
      prepared and organized will ensure a successful site visit. A detailed
      questionnaire is provided at the end of the article to help facilitate the
      process.

PMID- 17191549
TI  - Job descriptions and evaluations.

PMID- 17191550
TI  - The hybrid life.

PMID- 17191551
TI  - How to respond when JCAHO comes calling. Interview by John Disconsiglio.

PMID- 17191553
TI  - 30 methods of prevention are worth a pound of cure.

PMID- 17191552
TI  - Negotiating with statistics.

PMID- 17191554
TI  - Tubing misconnections: a perilous design flaw.

PMID- 17191555
TI  - Look before you leap. Which outsourcing options best suit your organization?

PMID- 17191556
TI  - Moving to a new pad.

PMID- 17191558
TI  - New surgical instruments and sets bring sterilization challenges.

PMID- 17191557
TI  - Cleaning up Supply chain data.

PMID- 17191563
TI  - Designing better physical environments for today's nurses.

PMID- 17191567
TI  - [Experimental study on repairing rabbit femoral condyles defect by small
      intestinal submucosa and HA-TCP compositions at different ratios].
AB  - OBJECTIVE: To study an optimal ratio of small intestinal submucosa (SIS) and
      (hydroxyapatite-tricalcium phosphate, HA-TCP, SIS/HA-TCP) compositions according
      to the effect of SIS/HA-TCP compositions with different ratios on repairing
      rabbit femoral condyle defect. METHODS: Thirty-six rabbits were made into bone
      defect models of 6 mm in diameter and 10 mm in depth in both sides of femoral
      condyles. Three different ratios of SIS/HA-TCP compositions (w/w: 1, 0. 5, 0. 25)
      were implanted into rabbit femoral condyle defect. After 2, 4, 8 and 12 weeks of
      operation, the repair effect was observed grossly. The histological evaluations
      were performed by histological scoring system and computer imaging analysis
      system. RESULTS: The amount of new bone formation in SIS/HA-TCP(0. 5) group was
      more than that in SIS/HA-TCP(1) and SIS/HA-TCP(0. 25) groups. Histological
      observation: In SIS/HA-TCP (1) group, few new bone formation was seen and bone
      defect was repaired in the 12th week. In SIS/HA-TCP (0.5) group, immature woven
      bone was found in the defect in the 2nd week; more immature woven bone appeared
      and formed trabeculae in the 4th week; the regenerated bone was vigorously
      growing into the interspaces of the implanted materials in the 8th week; the
      implanted materials was basically replaced by bony structure and the lamellar
      bone appeared in the 12th week. The results of SIS/HA-TCP (0. 25) group were
      similar to that of SIS/HA-TCP(0. 5) group. The histological scoring was higher in
      SIS/HA-TCP (0.5) and SIS/HA-TCP (0.25) groups than that in SIS/HA-TCP (1) group
      (P<0.05) in the 2nd, 4th, 8th, and 12th weeks. The scoring was higher in SIS/HA
      TCP (0.5) group than that in SIS/HA-TCP (0.25) group in the 2nd and 12th weeks
      (P< 0.05). In new bone formation and the degradation of HA-TCP, SIS/HA-TCP (0.5)
      and SIS/HA-TCPC (0.25) groups were superior to SIS/HA-TCP (1) group (P<0.05),
      SIS/HA-TCP (0.5) group was superior to SIS/HA-TCP (0.25) group (P<0.05).
      CONCLUSION: SIS/ HA-TCP (0.5) has better effects of repairing bone defect and it
      can be used as a reference ratio in constructing bone scaffolds.

PMID- 17191568
TI  - [Clinical application of medical grade calcium sulfate as a bone graft
      substitute].
AB  - OBJECTIVE: To investigate the clinical effect of medical grade calcium
      sulfate(Osteoset) as a bone graft substitute. METHODS: From December 2004 to May
      2005, 9 cases of bone defect(limb group) were repaired with Osteoset pellets;
      bone defect was caused by benign tumor in limbs, including 3 cases of fibroma
      xanthomas in humerus (1 case) and acetabulum (2 cases), 2 cases of bone cysts in
      humerus (1) and radius (1), 1 case of nonossifying fibroma, 1 case of ossifying
      fibroma and 2 cases of osteofibrous dysplasia in femurs. Five cases of lumbar
      posterolateral fusion (spine group) were treated with Osteoset pellets as
      autograft volume expander, including 2 cases of lumbar spinal stenosis, 2 cases
      of lumbar spondylolisthesis and 1 case of lumbar spondylolysis. Radiological
      method was used to evaluate the repair effect of Osteoset pellets. RESULTS: The
      mean follow-up time was 6.2 months (3 to 9 months). Osteoset pellets began to be
      absorbed after 1 to 3 months of operation, and were totally absorbed and replaced
      by osseous tissue after 4 to 6 months. No local recurrence was detected in limb
      group and the function of limbs was normal. At 6 months after operation, all
      patients in spine group got bony fusion. CONCLUSION: Medical grade calcium
      sulfate (Osteoset) is an ideal bone graft substitute with excellent bone repair
      effect.

PMID- 17191569
TI  - [Treatment of scaphoid nonunion with bone flap pedicled on the recurrent branch
      of radial artery to the styloid process].
AB  - OBJECTIVE: To report the clinical outcome of the transposition of the radial
      styloid bone flap pedicled on the recurrent branch of the radial artery in the
      treatment of scaphoid nonunion. METHODS: From March 2000 to June 2005, the
      procedure was done in 18 patients with scaphoid nonunion, a small bone flap (1.5
      cm x 3.5 cm x 0.5 cm) pedicled on the recurrent branch of radial artery to the
      styloid process was raised from the radial styloid process and grafted into the
      corresponding slot chiseled along the vertical axis of scaphoid crossing the
      fracture line. Of 18 patients, 15 were males and 3 were females, aging 18-39
      years. The locations were lumbar scaphoid in 11 patients and proximal scaphoid in
      7 patients, among whom 5 had presented avascular necrosis in the proximal
      fragments of the scaphoid. Pain occurred in the act of wrist motion, and became
      obvious in the case of dorsiextension and radial deviation. Compression pain was
      observed in the stuff nest. The wrist joint activity is subjected to limit. The X
      ray showed hardening and cystic degeneration at fracture end and obviously
      widening fracture line. RESULTS: The scaphoid fracture healed in all 18 cases,
      the 5 proximal scaphoid fracture fragments which had previously been necrosed
      survived, a mean healing time of scaphoid was 4 months. A follow-up of 1 to 5
      years revealed normal wrist motion without pain in all cases. The life and job
      was good every day. CONCLUSION: Transposition of the bone flap pedicled on the
      recurrent branch of the radial artery to the scaphoid is relatively simple and
      can effectively treat scaphoid nonunion and avascular necrosis with a great value
      in clinical application.

PMID- 17191570
TI  - [Treatment of femoral neck fractures with compressed screw and sartorius bone
      flap in youth or middle age].
AB  - OBJECTIVE: To study the application and the curative effect of compressed screw
      and sartorius bone flap in treating femoral neck fractures in youth or middle
      age. METHODS: From February 1996 to December 2004, 86 patients with femoral neck
      fracture were treated by open reduction compressed screw and sartorius bone flap,
      aging from 21 to 49 years. Fracture was caused by traffic accident in 35 cases,
      fall from height in 27 cases and fall in 24 cases. According to Garden
      classification, 23 cases were type II, 25 cases were type III, and 15 cases were
      type IV. We analyzed fracture healing and evaluate function by observation of the
      postoperative X-ray films. RESULTS: Of the 86 patients, 62 were followed up 6
      months to 7 years (2 years and 5 months on average). According to Weijie's
      criterion for nonunion and necrosis of femoral head, nonunion occurred in 4
      cases; the healing rate of fracture was 93.5%. In healed patients, necrosis of
      femoral head occurred in 7 cases (11.3%) after 3 years. The results of hip joint
      function evaluation were excellent in 44 cases, good in 8 cases, fair in 6 cases
      and poor in 4 cases; and the excellent and good rate was 83.9%. CONCLUSION:
      Compressed screw and sartorius bone flap was simple and effective for femoral
      neck fractures in youth or middle age.

PMID- 17191571
TI  - [Biomechanical evaluation of titanium mesh with anterior plate fixation or ilium
      autograft in anterior cervical decompression].
AB  - OBJECTIVE: To evaluate the biomechanical characteristics of titanium mesh with
      anterior plate fixation or ilium autograft in anterior cervical decompression.
      METHODS: Six fresh cervical spine specimens (C3-7) of young cadaver were used in
      the biomechanical test. After C5, C5,6 and C4-6 were given vertebrectomy, ilium
      autograft and titanium mesh with anterior plate fixation were performed. Their
      stabilities of flexion, bilateral axial rotation, the lateral bending and the
      extension were tested. Intact cervical spine specimens served as control group.
      RESULTS: Ilium autograft improved the stability of the unstable cervical
      vertebrae and decreased the flexion, the lateral bending or the extension,
      showing a significant difference when compared with control group (P<0.05).
      Whereas, axial rotational motion was decreased insignificantly (P>0.05). Titanium
      mesh with anterior plate fixation improved the stability of the unstable spine
      and decreased the flexion,the bilateral axial rotation,the lateral bending or the
      extension, showing a significant difference when compared with control group
      (P<0.05). CONCLUSION: The vertebrectomy and anterior cervical fusion by ilium
      autograft was the least stable construct of all modes tested,and the titanium
      mesh implantation is stable than the intact cervical sample.

PMID- 17191572
TI  - [Biomechanical influence of vertebroplasty with filling with autosolidification
      calcium phosphate cement in thoracolumbar osteoporotic fractures].
AB  - OBJECTIVE: To investigate the biomechanical influence of vertebroplasty using
      autosolidification calcium phosphate cement (CPC) on thoracolumbar osteoporotic
      fractures. METHODS: Four cadaver specimens with osteoporosis were applied to make
      spine unit. There were 2 females and 2 males, whose average age was 69 years. All
      underwent flexion-axial loading to result in vertebral body fracture. Following
      reduction, the middle fractured vertebral body were strengthened by the method of
      vertebroplasty, using CPC. Before fracture and after vertebroplasty, all were
      conducted biomechanical test. RESULTS: After being packed CPC to the space in the
      fractured vertebral body, the strength and stiffness in vertebroplastic group (2
      285+/-34 N, 427+/- 10 N/mm) were significantly higher than that in osteoporotic
      group (1 954+/-46 N, 349+/-18 N/mm) (P<0.05). The vertebral height changing in
      vertebroplastic group (5.35+/-0.60 mm) were significantly lower than that in
      osteoporotic group (5.60+/-0.70 mm) (P<0.05). And the fractured body increases
      its strength and stiffness by 16.92% and 22.31% respectively in comparison with
      its initial situation. CONCLUSION: After being injected CPC into bone trabecular
      interspaces, the fractured vertebral bodies can restore its strength and
      stiffness markedly.

PMID- 17191573
TI  - [Treatment of kyphosis deformity with pedicle subtraction osteotomy and short
      segment pedicle screw internal fixation].
AB  - OBJECTIVE: To assess the outcomes of pedicle subtraction osteotomy and short
      segment pedicle screw internal fixation in kyphosis deformity. METHODS: From June
      2001 to November 2003, 16 cases of kyphosis deformity were treated with pedicle
      subtraction osteotomy and short-segment pedicle screw internal fixation,
      including 11 males and 5 females and aging 24-51 years. The kyphosis deformity
      was caused by ankylosing spondylitis in 12 cases, old lumbothoracic fracture
      dislocation in 2 cases, and vertebral dysplasia in 2 cases. The disease course
      was 7-25 years with an average of 12.8 years. The whole spine radiographs were
      taken pre- and postoperatively. The sagittal balance was assessed by measuring
      thoracic kyphosis angle, lumbar lordosis angle, sacrohorizontal angle and
      distance between posterosuperior point of S1 and the vertical line. The clinical
      outcomes were assessed by Bridwell-Dewald scale for spinal disorders. RESULTS:
      The mean follow-up period was 25. 6 months. The mean bleeding was 1100 ml.
      Satisfactory bone graft healing was achieved at final follow-up. Complications
      were paralytic intestinal obstruction in 1 case, dura laceration in 1 case, and
      temporary lower limb paralysis in 2 cases. Final follow-up radiograph showed an
      increase in lumbar lordosis angle from 9.6+/-16.4 degrees to 42.6 14.3 degrees
      (P<0.05), whereas thoracic kyphosis angle remained relative stable. The distance
      between posterosuperior point of S1 and the vertical line was decreased from
      97.5+/-45.6 mm to 10.7+/-9.6 mm (P < 0.05). Satisfactory clinical outcome was
      achieved by evaluating the changes of pain, social and working status.
      CONCLUSION: Pedicle subtraction osteotomy and short-segment pedicle screw
      internal fixation is effective for correction of kyphosis deformity.

PMID- 17191574
TI  - [Repairing widespread traumatic soft tissue defects in lower limb with free
      latissimus dorsi muscle-skin flaps].
AB  - OBJECTIVE: To explore the results of repairing widespread traumatic soft tissue
      defects in the heels and adjacent regions with free latissimus dorsi muscle-skin
      flaps. METHODS: From March 1998 to May 2005, 10 cases of widespread traumatic
      soft tissue defects in the heels and adjacent regions were repaired with free
      latissimus dorsi muscle-skin flaps; Of the 10 patients, 9 were male and 1 was
      female, whose ages ranged from 32 to 60 years, and the disease course was 2 hours
      to 2 months. The defect was by plough-machine injury in 5 cases, by crush injury
      in 2 cases, by snake injury in 2 cases, and electricity injury in 1 case. Eight
      cases of defects involved in the posterior of heel and leg, the defect area
      ranged from 21 cm x 12 cm to 35 cm x 15 cm; 2 cases had widespread soft tissue
      defects on heel, ankle, sole and dorsal foot, and the defect area was 27 cmX 14
      cm and 30 cm x 21 cm respectively. All cases were accompanied by the exposure of
      bone; 6 cases by fracture; 4 cases by open infection of ankle joint; and 2 cases
      by injuries of the posterior tibial vessel and the tibial nerve. The sizes of the
      dissected flap ranged from 25 cm x 14 cm to 33 cm x 24 cm. The donor sites were
      covered by large mid-thickness flap. RESULTS: There were no postoperative
      complication of vascular crisis and infection. Ten flaps survived completely and
      the wounds healed by first intention. After a follow-up of 3 to 24 months, five
      cases received two-stage plastic operation because bulky flaps bring some trouble
      in wearing shoes. In 5 cases of reconstructed sensation, two cases recovered pain
      and temperature sensation. All cases recovered the abilities to stand and walk
      without ulcer complication. CONCLUSION: The free latissimus dorsi muscle-skin
      flap is an ideal flap for repairing widespread traumatic soft tissue defects and
      infectious wounds with muscle defects and bone exposure in the heel and adjacent
      regions, because it has such advantages as adequate blood supply, big dermatomic
      area, and excellent ability to resist infection.

PMID- 17191575
TI  - [Clinical application of improved island skin flap with distally-based sural
      nerve nutrient vessels].
AB  - OBJECTIVE: To report the clinical result of the improved island skin flap with
      distally-based sural nerve nutrient vessels in repairing skin defect in the heel,
      ankle or foot. METHODS: From August 2004 to April 2005, 15 patients with skin
      defect in the heel, ankle or foot at distal part were treated by the improved
      island skin flap with distally-based of sural nerve nutrient vessels. Of 15
      flaps, 12 were simplex flaps and 3 were complex flaps. These flap area ranged
      from 7 cm x 6 cm to 11 x 8 cm. The donor sites were sutured directly and covered
      with free flap. RESULTS: All flaps survived without flap swelling and disturbance
      of blood circulation. The wounds of donor and recipient sites healed by first
      intention. The follow-up period ranged from 3 to 6 months. The texture of flap
      was soft and the color of flap was similar to that of normal skin. The foot
      function was excellent. CONCLUSION: The improved island skin flap with distally
      based sural nerve nutrient vessels is an ideal skin flap for repairing skin
      defect in the heel, ankle or foot distal part in clinical. The operation is
      simple and need not to anastomose blood vessel.

PMID- 17191577
TI  - [Effects of immunosuppressants on cultured rat macrophages and Schwann's cells].
AB  - OBJECTIVE: To explore the effects of several immunosuppressants on the cell
      numbers of cultured rat macrophages and Schwann's cells. METHODS: The macrophages
      and Schwann's cells were cultured from the new-born Wistar rats. Different
      concentrations of methylprednisolone (10(-3), 10(-4), 10(-6) and 10(-8) mol/L),
      CsA (10(-5), 10(-6), 10(-7) and 10(-8) mol/L) and FK506 (10(-6), 10(-7), 10(-8)
      and 10(-9) mol/L) were administrated to the cells, while control group was given
      no drugs. Twenty-four, 48 and 72 hours after administration, the cells from
      different concentrations were measured with MTT methods respectively. The results
      were compared and analyzed statistically. RESULTS: Only high concentration
      methylprednisolone (10(-4) mol/L) and a certain range of concentrations of CsA
      (10(-6), 10(-7) and 10(-8) mol/L) and FK506 (10(-7), 10(-8) and 10(-9) mol/L) can
      provide protection to cultured rat macrophages. Under most concentrations, CsA
      and FK506 had no effects on the cell number of cultured rat Schwann's cell. Only
      with high concentration CsA (10(-5) mol/L) and methylprednisolone (10(-3) mol/L)
      could significantly decreased the cell number of Schwann's cell. Long time (72
      hours) and low dosage (10(-8) mol/L) administration of methylprednisolone could
      significantly protect Schwann's cell. CONCLUSION: High concentration
      methylprednisolone and some certain concentration CsA and FK506 can protect
      cultured rat macrophages. But high concentration CsA and methylprednisolone
      prohibit the proliferation of Schwann's cells. Only long time and low dosage
      methylprednisolone can protect cultured rat Schwann's cells.

PMID- 17191576
TI  - Recombinant human platelet-derived growth factor enhances repair of cutaneous
      full-thickness excision by increasing the phosphorylation of extracellular signal
      regulated kinase in diabetic rat.
AB  - OBJECTIVE: To investigate the possible signaling mechanisms by which recombinant
      human platelet-derived growth factor (rhPDGF) accelerated healing of cutaneous
      wound in diabetic rats. METHODS: Four full-thickness skin wounds were incised in
      the back of 26 male Wistar diabetic rats. The wounded rats were divided into 3
      groups (7 or 8 rats each group). One group without treatment was used as a
      control, and the other 2 groups were treated with rhPDGF at a dose of 7.0
      microg/cm2 wound or vehicle (DMSO/0.9% NaCl, vol/vol 1:1) from 1 to 14 days. The
      wound healing was evaluated by the measurements of the wound volume and area.
      Immunofluorescent and immunohistochemical staining were used to examine the
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and the
      expression of proliferative cell nuclear antigen (PCNA), respectively. RESULTS:
      Granulation tissue appeared in the bed of wound after injury. The number of blood
      capillary buds and fibroblasts was greater in the rhPDGF-treated group than that
      in the other 2 groups. A lot of inflammatory cells infiltration and collagen
      deposition were observed in the wound. The wound-volume in the rhPDGF-treated
      group was smaller than that in control group (P < 0.05). The reepithelialization
      rate in rhPDGF-treated group was higher than that in the other 2 groups at 7 days
      after injury (P < 0.05). The expression of PCNA in reparative cells was higher in
      rhPDGF-treated group than in control group or vehicle-treated group at 3,7 days
      after injury (P < 0.05). The phosphorylation of ERK1/2 was stronger in rhPDGF
      treated group than that in control group or vehicle group at 7 and 14 days after
      injury (P < 0.05). CONCLUSION: These results suggest that rhPDGF accelerates
      wound healing and improves healing quality by increasing the phosphorylation of
      ERK1/2.

PMID- 17191578
TI  - [Pathological changes in neuromuscular junction during ischemia-reperfusion in
      rat skeletal muscle].
AB  - OBJECTIVE: To investigate the pathological changes in the neuromuscular junction
      during ischemia-reperfusion (IR) in the skeletal muscle. METHODS: Forty-eight
      healthy adult Wistar rats (24 male, 24 female) were equally randomised into the
      following 6 groups: Group A (control group): no ischemia-reperfusion; Group B:
      ischemia by clamping the blood vessels of the right hindlimb for 3 hours; Group
      C: ischemia by clamping for 4.5 hours; Group D: ischemia by the clamping for 4.5
      hours followed by reperfusion for 1.5 hours; Group E: ischemia for 4.5 hours
      followed by reperfusion for 24 hours; and Group F: ischemia for 4. 5 hours
      followed by reperfusion for 2 weeks. Then, the medial head of the gastrocnemius
      muscle flap model was applied to the right hindlimb of each rat. The medial head
      of the gastrocnemius muscle was isolated completely,leaving only the major
      vascular pedicle, nerve and tendons intact. The proximal and distal ends
      (tendons) were ligated while the vessel pedicle was clamped. And then, Parameters
      of the muscle (performance, contraction index, colour, edema, bleeding) were
      observed. The muscle harvested was stained with gold chloride (AuCl3) and the
      enzyme histochemistry assay (succinate dehydrogenase combined with acetylcholine
      esterase) was performed. Morphology and configuration of the neuromuscular
      junction were observed during the ischemia-reperfusion injury by means of the
      AuCl3 staining. The result of the enzymehistochemical reactions was
      quantitatively analyzed with the computer image-analysis system. And then,
      additional 5 rats were prepared for 3 different models identical with those in
      Groups A, C and E separately. The specimens were harvested from each rat and were
      stained with HE and AuCl3, and they were examined under the light microscope.
      RESULTS: During the period of ischemia, the skeletal muscle of Group B showed the
      colour of purple and edema. The colour and edema became worse in Group C,while
      dysfunction of elasticity and contraction appeared obviously with plenty of dark
      red hemorrhagic effusion at the same time. After reperfusion,the color and edema
      of muscle in Group D became improved while the elasticity and function of
      contraction was not improved. Hemorrhagic effusion of Group D turned clearer and
      less than Group C. Group E was similar to Group D in these aspects of muscle
      except for much less hemorrhagic effusion. Skeletal muscle in Group F showed
      colour of red alternating with white, adhesion, contracture of muscle, exposure
      of necrotic yellow tissue and almost lost all its functions. The AuCl3 staining
      showed that during IR, necrosis of the myocytes was followed by degeneration of
      their neuromuscular junctions, and finally the nerve fibers attached to these
      neuromuscular junctions were disrupted like the withering of leaves. The enzyme
      histochemistry assay showed that there was no significant difference in the level
      of acetylcholine esterase between the ischemic group (Groups B and C) and the
      control group (Group A) (P>0.05). However, the level of acetylcholine esterase in
      all the reperfused groups (Groups D, E and F) decreased significantly when
      compared with the control group (Group A) and the ischemic groups (Groups B and
      C) (P<0.01). CONCLUSION: The distribution of the nerve fibers and the
      neuromuscular junctions in the mass of the muscles is almost like the shape of a
      tree. The neuromuscular junction seems to be more tolerant for ischemia than the
      myocyte. Survival of the neuromuscular junction depends on its myocytes alive.
      Therefore, an ischemia-reperfusion injury will not be controlled unless an
      extensive debridement of the necrotic muscle is performed.

PMID- 17191579
TI  - [Effect and significance of tetrandrine on epidermal growth factor and its
      receptor in the lung of congenital diaphragmatic hernia rat model].
AB  - OBJECTIVE: To investigate the effect of the traditional Chinese medicine
      "Tetrandrine"(TET) and its significance on epidermal growth factor (EGF) and its
      receptor (EGFR) in the lung of nitrofen-induced congenital diaphragmatic hernia
      (CDH) rat model. METHODS: Twenty female rats were given maternal administration
      of a single oral dose (115 mg/rat) of nitrofen to induce CDH at 9.5 days after
      pregnancy and were divided into normal solution group (NS, n=5), dexamethasone
      group (Dex, n=5), tetrandrine group (TET, n=5) and Dex+TET group (n=5) at 18.5
      days; 4 rats were given edible oil as controls. All fetuses were delivered by
      cesarean section at 21.5 days. Lung histologic evaluations and EGF, EGFR
      immunohistochemical staining and image analysis were performed. RESULTS: CDH was
      observed in 64 of the 137 rat fetuses (46.7%) in the experimental groups; no CHD
      was observed in 36 rat fetuses of control group. The lungs of CDH fetuses showed
      marked hypoplasia in NS group, in contrast to improved mesenchymal
      differentiation in that of Dex, TET, Dex+TET groups. The expression of EGF was
      weaker and weaker and that of EGFR was stronger and stronger as following order:
      NS, TET, DEX, T+D and control groups; showing significant differences between
      them (P<0.05). CONCLUSION: Prenatal TET administration shows marked improvement
      in pulmonary hypoplasia through pre-regulating crest-time of EGF expression and
      up-regulating EGFR expression in the lungs of nitrofen-induced CDH rat model. A
      combination of TET and Dex would generate evident synergistic effect.

PMID- 17191580
TI  - [In vitro study on induction systems for marrow mesenchymal stem cells to
      chondrocytes].
AB  - OBJECTIVE: To study the effect of transforming growth factor beta1 (TGF-beta1)
      and insulin-like growth factor 1 (IGF-1) during the induction course from marrow
      mesenchymal stem cells (MSCs) to chondrocytes and to observe the effect of cell
      density on cell induction. METHODS: Differential time adherent methods were used
      to purify MSCs obtained from the bone marrow of Kunming mice. MSCs were cultured
      under special conditions to induce them to differentiate into chondrocytes.
      Toluidine blue staining and immunofluorescence were used to identify those
      induced chondrocytes. TGF-beta1 and IGF-1 were used individually or in
      combination under two different culture patterns: pellet culture and monolayer
      culture. According to different growth factors, experiment included 3
      experimental groups (TGF-beta1 + IGF-1 group, 10 ng/ml and 50 ng/ml respectively;
      TGF-beta1 group, 10 ng/ml; and IGF-1 group, 50 ng/ml) and control group (without
      growth factor). In TGF-beta1 + IGF-1 group, toluidine blue staining and
      immunofluorescence staining were carried out at 14 days and 21 days. The effect
      of TGF-beta1 and IGF-1 on the expression of collagen II gene was detected by RT
      PCR at 7, 14 and 21 days of induction; the expressions of collagen II were
      compared between two culture patterns. RESULTS: In TGF-beta1 +-IGF-1 group, the
      histological examination and immunofluorescence showed that those inducted
      chondrocytes could express collagen II at 14 days. The gel electrophoresis
      results showed that the fragment of collagen II gene was seen in TGF-beta1 +IGF-1
      group and TGF-beta1 group and that no fragment of collagen II gene was seen in
      IGF-1 group and control group. The expression of collagen II gene was stronger in
      TGF-beta1+ IGF-1 group than in TGF-beta1 group, showing significant difference
      (P<0. 05). Cells expressed more collagen II under pellet culture than under
      monolayer culture. CONCLUSION: IGF-1 could enhance the effect of TGF-beta1 during
      the induction course from MSCs to chondrocytes. A certain extent of high cell
      density is more effective for MSCs to differentiate into chondrocytes.

PMID- 17191581
TI  - [Identification of glial cell line-derived neurotrophic factor recombinant
      retroviral vector and establishment of its packaging cell line PA317].
AB  - OBJECTIVE: To identify glial cell line-derived neurotrophic factor (GDNF)
      recombinant retroviral vector and to establish its packaging cell line PA317.
      METHODS: PA317 cells were transfected with recombinant retroviral vector pLXSN
      GDNF using liposomes. The recombinant retroviral particles were then harvested
      from culture media of G418 resistant transfected cells and analyzed using RT-PCR.
      Virus titers in supernatants were investigated. RESULTS: Sequencing date
      indicated that GDNF gene was exactly identical to the sequence in the GeneBank.
      PA317 cells were transfected with recombinant retroviral vector pLXSN-GDNF using
      liposomes, and virus titers in supernatants harvested from culture media of (G418
      resistant transfected cells were 10(4)10(5) CFU/ml. CONCLUSION: Packaging cell
      line PA317/pLXSN-GDNF was established.

PMID- 17191582
TI  - [A new method of establishing experimental model of chronic myocardial infarction
      by incision below xiphoid process in black goats].
AB  - OBJECTIVE: To establish an effective model of myocardial infarction in black goat
      so as to provide a safe, convenient and credible model of myocardial infarction
      for treatment and research. METHODS: Sixteen black goats were made chronic
      myocardial infarction by ligation of far end of left anterior descending coronary
      artery through incision below xiphoid process. Electrocardiogram (ECG) and serum
      myocardial enzymes were investigated before and after occlusion.
      Echocardiographic measurements were performed, and left coronary artery
      angiography was performed with digital subtraction angiography (DSA) before
      infarction and 6 weeks after infarction. The myocardial ultrastructure were
      observed. RESULTS: All goats survived more than 6 weeks. ECG showed ambulatory
      change, ST-segment elevated half an hour after occlusion and pathologic Q waves 6
      weeks after infarction, CK-MB significantly increased. Echocardiographic indexes
      showed significant decrease of maximal peak A, percent wall thickening(WHT) and
      ejecting fraction (EF), increase of end-systolic volume (ESV), end-diastolic
      volume (EDV), and dilation of left ventricle. DSA showed block or decrease of
      perfusion of far end of left anterior descending coronary artery. CONCLUSION: It
      is safe, convenient and credible to establish model of myocardial infarction by
      ligation of far end of left anterior descending coronary artery through incision
      below xiphoid process in black goat.

PMID- 17191583
TI  - [Establishment of eukaryotic cell line stably expressing soluble human leucocyte
      antigen G1 by nucleofection].
AB  - OBJECTIVE: To establish a eukaryotic cell line that can express soluble human
      leucocyte antigen G1 (sHLA-G1) stably. METHODS: The recombinant plasmid pcDNA3
      sHLA-G1 is transfected by a novel nonviral, electroporation-based gene transfer
      method termed nucleofection into the host cell lymphoblastoid cell line (LCL)
      721.221 which does not express any HLA-classical I molecules. After selection by
      G418, the cell line stably expressing sHLA-G1 is identified by RT-PCR and Dot
      ELISA with HLA-G1 specific monoclonal antibody MEM-G/9. RESULTS: The efficiency
      of transfection for LCL721. 221 is about 14% by nucleofection. The specific band
      for sHLA-G1 was found by RT-PCR assay from the transfections and the protein of
      sHLA-G1 in the supernatant of the transfections was detected by Dot-ELISA assay.
      Both confirmed that the eukaryotic cell line expressing sHLA-G1 has been
      established successfully at genic and proteinic levels. CONCLUSION: In this
      study, the eukaryotic cell line expressing sHLA-G1 have been established
      successfully by nucleofection.

PMID- 17191584
TI  - [Development of modern tissue banks and quality control].
AB  - OBJECTIVE: To review the development and quality control of modern tissue banks.
      METHODS: The rules, regulations and the management literatures about tissue banks
      were extensively and comprehensively reviewed. RESULTS: Tissue banks have a
      significant progress and are developing to concentration, industrialization and
      standardization gradually. Quality control is being paid more attention in modern
      tissue banks. CONCLUSION: Modern tissue banks will have a good future and the
      quality control must be intensified.

PMID- 17191585
TI  - [Study on bovine spongiform encephacitis and current status of safety control of
      medical devices deriving from animals].
AB  - OBJECTIVE: To introduce the basic information about mad cow disease and the
      current status of safety control of medical devices derived from mammalian animal
      tissues. METHODS: Literature concerned was reviewed intensively. RESULTS: Mad cow
      disease also known as bovine spongiform encephacitis (BSE), is generally
      considered from the same source of Scrapie, and they are caused by the same kind
      of sponginess brain tissue pathological changes. Mad cow disease is caused by the
      misfolding of a small protein called Prion. This disease has the character of
      slowly breaking down the central neuron system of animals. CONCLUSION: Further
      researches can provide evaluation for safety considerations of medical devices
      deriving from animal.

PMID- 17191586
TI  - [Research advance of gene therapy for peripheral arterial disease using
      hepatocyte growth factor].
AB  - OBJECTIVE: To introduce the studies on gene therapy for peripheral arterial
      disease (PAD) using plasmid DNA encoding human hepatocyte growth factor(HGF)
      gene. METHODS: Recent articles including preclinical and clinical studies were
      reviewed. RESULTS: Intramuscular injection of human HGF plasmid DNA into rat,
      rabbit, dog and diabetic hindlimb ischemic models, resulted in a significant
      increase in capillary density, blood flow and blood pressure. but no influence on
      tumor growth in mice. A clinical trial was performed in ischemic limbs of 6
      critical limb ischemic patients, the result showed that no side effect caused by
      gene transfer was detected in all 6 patients. The pain scale and long diameter of
      ischemic ulcers were reduced. CONCLUSION: Intramuscular injection of naked HGF
      plasmid DNA could be a safe and potential treatment for PAD.

PMID- 17191587
TI  - [Cardiac arrhythmias: a true challenge for community hospitals].

PMID- 17191588
TI  - [How to carry out the indications of cardiac resynchronization therapy in
      practice?].
AB  - Recent studies have demonstrated that cardiac resynchronization therapy diminish
      morbidity and mortality of patients with heart failure, who remain symptomatic
      despite an optimal medical treatment and who have a wide QRS. However, 30% of
      patients are non-responders. Hence, echocardiography constitutes an interesting
      tool for the diagnosis of asynchrony. Different echocardiographic indices predict
      response to cardiac resynchronization therapy. In this article, a practical
      approach is proposed for these patients.

PMID- 17191589
TI  - [Pacemakers and defibrillators: what should we know about home monitoring?].
AB  - Cardiac stimulators and defibrillators dispose of diagnostic capabilities. Home
      monitoring permits to have information about the cardiac rhythm of the patient
      and about the function of the pacemaker or the defibrillator. Technical aspects,
      safety and legal issues of home monitoring are discussed in this article.

PMID- 17191590
TI  - [Acquired long QT syndrome: a dominant problem?].
AB  - QT prolongation is essentially of pharmacologic origin. It is principally linked
      to a block of the outward potassium current Ikr, with as a consequence a
      prolongation of the repolarisation causing early after potentials and re-entry.
      The term "repolarisation reserve" expresses the variable risk of arrhythmia among
      individuals under the same drug blocking Ikr. This reserve can be altered under
      various pathologic or genetic conditions. A series of risk factors (bradycar
      Torsades de pointes} were described in 1966 by Dessertenne. They are due to a
      perturbation of ventricular repolarisation causing QT prolongation on surface
      ECG. Acquired dia, electrolytic disorders, cardiac disease, neurologic disorders,
      nutrition troubles, female gender) can play a role as well as the metabolic
      processing of pharmacological agents by Cytochrome P450 and various inhibitors or
      inductors of this system which can influence the half life of drugs. The list of
      drugs involved is continuously increasing: antiarrhythmics, antihistamines,
      psychotropics, anti-infectious are the main categories involved. Risk prediction
      is difficult particularly for non cardiovascular drugs and a low risk incidence.
      An other risk is to exclude patients from the benefit of an efficient drug for a
      serious but not frequent risk, at last an industrial risk for the manufacturer
      when a drug is withdrawn lately when important quantities of money have already
      been invested for its development. The diagnosis of torsades is easy on standard
      ECG although QT measurement and its heart rate variation remain uneasy. The
      treatment of the arrhythmias is based on heart rate acceleration by Isoprenaline
      or intravenous pacing and on intravenous administration of magnesium.

PMID- 17191591
TI  - [Cardiac resynchronisation therapy in practical terms].
AB  - Cardiac resynchronisation therapy, associated with defibrillation therapy or not,
      has emerged as an effective treatment in heart failure patient. Cardiac
      resynchronisation technique can be difficult despite improvements in the
      implantation materials. Knowledge of the anatomy of the coronary venous network,
      especially the coronary sinus ostium and the distribution of the lateral branches
      could simplify device implantation. Coronarography with anterograde opacification
      of the coronary venous system could facilitate pre-selection of appropriate tools
      for coronary sinus and marginal vein catheterisation.

PMID- 17191593
TI  - [Local registry of pacemakers implantations: proposals to decrease the infectious
      risk].
AB  - The complications of definitive cardiac stimulation must not be forgotten or sub
      estimate. The aim of our Registry is to compare the complications of the
      implantation of a pacemaker in the national and international literature. The
      assessment of our professional practices has been achieved. We suggest improved
      procedures. The late complications are not exactly known.

PMID- 17191592
TI  - [Atrial flutter ablation: initial experience in a general hospital].
AB  - BACKGROUND: Right atrial flutter has a relatively high incidence. It is often
      symptomatic and can have a poor outcome particularly in case of thrombo-embolic
      events. AIM OF STUDY: We evaluate the results of radiofrequency catheter ablation
      for right atrial flutter since the introduction of this technique inour hospital.
      METHODS: The 28 first patients referred in our institution for atrial flutter and
      relevant for cavo-tricuspid isthmus ablation were enrolled. Ablation used a 8 mm
      tip electrode catheter and one or two conventional diagnostic catheters. The goal
      of ablation was complete bidirectional isthmus block. RESULTS: The first-line
      success rate was 96 percent with 4 percent early flutter recurrence. The mean
      duration of radiofrequency current applications was 652 +/- 409 seconds. No
      complication was observed. CONCLUSION: This results are comparable with the
      published data and encourage the development of basic ablation procedures and
      maintenance of rhythmic competence in general hospital inside medical network.

PMID- 17191594
TI  - [Cardioverter-defibrillator implantation and follow-up in a non-university
      hospital].
AB  - Implantable cardioverter-defibrillators (ICD) have emerged as a major treatment
      for life threatening ventricular arrhythmias. This technique is available in
      France in all the university hospitals and, with the favor of the new regulation,
      in some qualified private centers. However, ICD implantation and follow-up in a
      non-university hospital is infrequent. This study reports long-term results
      following ICD implantation in 152 patients (age 61+/-13 years). The vast majority
      (49%) of the patients were implanted for post-infarction ventricular tachycardia
      and 17% in primary prevention for left ventricular dysfunction. An appropriate
      therapy was delivered in 83 patients including 68 (81%) treated by
      antitachycardia pacing without the need for a cardioversion shock. An
      inappropriate shock was observed in 13 patients (9%). Because of iterative
      shocks, catheter radiofrequency ablation was proposed among 9 patients, with a
      success in 8. In conclusion, the technique of the implantable defibrillator can
      be performed in a non-university hospital with acceptable results. The increase
      in the ICD number in France implies that there is a need for collaboration
      between non-university and university hospitals in managing routine and emergency
      follow-up.

PMID- 17191595
TI  - [Long-term outcome of acute myocardial infarction treated with primary
      angioplasty. Experience of a public center in Alsatia-France].
AB  - OBJECTIVES: Estimation of long-term outcome for patients suffering from acute
      myocardial infarction treated with primary angioplasty in an alsatian public
      center. PATIENTS AND METHODS: Two-hundred and ninety-eight patients who underwent
      an urgent coronarography in a non-university center, with a view to immediate
      angioplasty, between January 1999 and December 2001. RESULTS: Two-hundred and
      sixty-four patients (88.6%) were actually treated with urgent angioplasty, which
      has been successful in 87.1% of cases. Hospital mortality was of 7.7%. The
      population was composed of 16.4% patients older than 75 and of 11.7% patients
      with Killip 3 or 4 at admission. Mean follow-up was 34 months, lost to follow-up
      rate was of 4.7%. The global survival rate was of 78.9% and event-less survival
      rate of 41.9%. CONCLUSION: Our results confirm the efficiency of angioplasty in
      real-life conditions as well at short-term as at long-term.

PMID- 17191596
TI  - [Heart failure patient management: evolution, organization, application on a
      local scale].
AB  - Heart failure is a severe disease which prevalence and incidence are steadily
      growing, with high morbidity and mortality rates, and responsible for significant
      financial cost. This evolution requires our therapeutic approach to be modified,
      by favouring multidisciplinary management and including patient education. The
      proof of the effectiveness of these measures is brought by many studies, and
      therapeutic education is now recommended by the European Society of Cardiology.
      This new approach of management is set out according to various procedures. In Le
      Creusot, the therapeutic unit of heart failure management was created in
      September 2004 and operate on a day hospital pattern. The results are
      satisfactory knowing that the average duration of spells fell by 33% after one
      year. Further local initiatives are spreading and need shall arise to pooling
      equipment and personnel as well as reinforcing collaboration between public and
      private professionals in order to improve heart failure patients' management. In
      the meantime a more sustained involvement of the authorities is to be hoped.

PMID- 17191597
TI  - [Barriers and opportunities for social participation in health: the main social
      actors' perceptions].
AB  - OBJECTIVE: Analysing barriers to and opportunities for user involvement as
      perceived by the social actors involved in implementing Colombian policy
      regarding social participation in health. METHODS: An exploratory qualitative
      study was carried out in the Colombian towns of Tulua and Palmira between 2000
      and 2001. There were 10 focus groups having 260 users and leaders. Semi
      structured individual interviews were given to health personnel (36) and policy
      makers (3). Narrative content, mixed categories and data segmentation by
      informants and topics were then analysed. RESULTS: Users and leaders considered
      their own lack of knowledge, apathy and fear of revenge as barriers for
      participation. However, there were institutional factors such as lack of
      institutional transparency, limited receptiveness and responsiveness regarding
      participation. These opinions were shared by policy-makers. Most health personnel
      identified users' knowledge and attitudes as barriers for participation; few
      mentioned any institutional barriers such as the behaviour of personnel,
      institutional opacity and the lack of resources for fostering work in the
      community. Opportunities for participation were described in terms of suitable
      and possible scenarios. Users perceived their great ability to achieve change
      through their direct participation appeared to them as presenting an important
      opportunity. CONCLUSIONS: Users' and leaders' perceptions of the current barriers
      and opportunities seemed to show that they are critical of their own reality and
      constitute important potential actors for becoming key interlocutors with
      institutions and the state. A similar attitude would be necessary on the part of
      institutional actors to build a real and permanent participatory culture.

PMID- 17191598
TI  - [Evaluating a programme for strengthening family-caregivers' ability to care for
      the chronically ill].
AB  - OBJECTIVE: The study evaluated the effectiveness of the "Caring for the
      caregivers" programme which was designed to strength family caregivers' ability
      to care for people suffering from chronic disease. METHODOLOGY: The study used a
      quasi-experimental design, having study and control groups, and measured caring
      ability before and after the intervention. 250 family caregivers were included in
      the study. RESULTS: The results included a description of the caregiver groups in
      terms of gender, age, family relationship, caring time and care receiver's
      dependence level. They also included initial and final levels regarding caring
      ability in each group, as well as comparing them to each other. Similarities were
      found in gender and responsibility for caring for younger people; differences
      were found in the service of origin, care-receiver functionality, accumulated
      experience and age. Caring ability was homogeneous in groups before the
      intervention but different in total level and patience following the programme.
      DISCUSSION: The findings agreed with the literature in terms of gender
      distribution, age, home assistance and caregivers' low levels of ability in terms
      of taking care of a family member suffering from chronic disease. The results
      suggested that the "Caring for the caregivers" programme has helped to increase
      caregivers' caring abilities and in doing so provided an option regarding the
      chronically ill which must be further explored within a Latin-American setting.

PMID- 17191599
TI  - [Unit cost variation in a social security company in Queretaro, Mexico].
AB  - OBJECTIVE: Comparing unit cost variation between departments and reasons for
      consultation in outpatient health services provided by a social security company
      from Queretaro, Mexico. METHODS: A study of costs (in US dollars) was carried out
      in outpatient health service units during 2004. Fixed unit costs were estimated
      per department and adjusted for one year's productivity. Material, physical and
      consumer resources were included. Weighting was assigned to resources invested in
      each department. Unit cost was estimated by using the micro cost technique;
      medicaments, materials used during treatment and reagents were considered to be
      consumer items. Unit cost resulted from adding fixed unit cost to the variable
      unit cost corresponding to the reason for consulting. Units costs were then
      compared between the medical units. RESULTS: Unit cost per month for diabetic
      treatment varied from 34.8 US dollars, 32,2 US dollars to US 34 US dollars, pap
      smear screening test costs were 7,2 US dollars, 8,7 US dollars and 7,3 US dollars
      and dental treatment 27 US dollars, 33 US dollars, 6 and 28,7 US dollars.
      CONCLUSION: Unit cost variation was more important in the emergency room and the
      dental service.

PMID- 17191600
TI  - [Breast cancer in the Pedro Claver hospital in Bogota, 2004].
AB  - OBJECTIVE: Reviewing new cases of breast cancer attending Clinica San Pedro
      Claver, Bogota, Colombia, during 2004. MATERIAL AND METHODS: Patients were
      recruited from the meeting offered by the service which all new breast cancer
      patients attend. Hospitalised patients, outpatients, clinical meetings,
      consulting rooms, operating room schedules and pathology reports were consulted
      to ensure that a true cross-section was included. The information was recorded in
      an Excel file and analysed using EPIINFO software. RESULTS: Breast cancer was
      diagnosed in 220 patients. Average age was 59; 18 % were aged les than 40.
      Infiltrative ductal cancer (84,1 %) was the most frequently found histological
      type. Distribution by stage showed that most patients presented stage 0 to stage
      II (62,7 %). Tumours measured 2 or more centimetres in 78 % of the patients. 83 %
      of the patients had surgery and 60 % chemotherapy. However, these scores were
      lower in patients aged more than 69 (58,3 % for surgery and just 13,9 % for
      chemotherapy, p<0.05). Hormonotherapy was prescribed for 40,9 % of the patients.
      CONCLUSIONS: Breast cancer is the more frequent found carcinoma. Clinica San
      Pedro Claver's cancer records revealed the personal, clinical and therapeutic
      characteristics of new female breast cancer patients attending this hospital
      during 2004. Most patients were in early breast cancer stages; however, detecting
      a greater number of non-palpable lesions should still be stressed. Treating
      elderly patients (those older than 69 regarding that found for younger patients)
      and the quality of procedures, hormonal receptor reports and therapeutic decision
      should also be evaluated in an attempt to explain the low percentage of hormone
      treatment currently being used in the hospital.

PMID- 17191601
TI  - [Using antibiotics in urinary tract infection in a first level of attention
      health care unit in Bogota, Colombia].
AB  - OBJECTIVES: Describing using antibiotics for urinary tract infection in a first
      level of attention health care unit. METHODS: This was an observational and
      descriptive study of a cohort of register-based patients attending the
      Universidad Nacional de Colombia's Health Service Unit (UNISALUD) diagnosed as
      suffering urinary tract infection between July 2002 and June 2003. RESULTS: 6,3 %
      urinary tract infection incidence was found, especially affecting women (84,4 %).
      The signs and symptoms were the same as those usually found in this disease. 58%
      corresponded to lower tract infection, 36 % to non-specific infection, 4 % to
      infection during pregnancy and 2 % to upper tract infection. The following
      uropathogens were isolated: E. coli (88.9%), Proteus spp. (5,1%), Klebsiella spp.
      (3,7 %), Enterobacter spp. (1%), Citrobacter spp. (1 %) and Staphylococcus
      saprophyticus (0,3 %). There was great variability in the antibiotic schemes
      being prescribed. Nitrofurantoin, Trimethoprim-sulfamethoxizole and
      Fluoroquinolones were the most prescribed, per defined daily dose; these
      antibiotics presented low susceptibility for the uropathogens so isolated. There
      was a 4:1 ratio of empirical treatment respecting confirmed ones. 98 % of the
      cases corresponded to patients suffering from a single event or having just 1 to
      2 recurrences. DISCUSSION The urinary tract infection studied here presented a
      similar epidemiological profile to that usually found in the general population.
      The isolated microorganism's low susceptibility to the prescribed antibiotics
      could reflect inappropriate use of antibiotics by the health service, inducing
      selective pressure on bacterial resistance.

PMID- 17191602
TI  - [Disability in a displaced population in Cauca, Colombia].
AB  - OBJECTIVE: Estimating the prevalence of disability in a displaced Colombian
      population. METHODS: A descriptive prevalence study was carried out amongst 165
      displaced families in the city of Popayan, Cauca, Colombia between June and
      December 2003. The information was collected via a questionnaire regarding socio
      demographic and biological variables. RESULTS: There was 8.5 % disability in the
      population being studied. Regarding the type of disability 5.6 %, 0.7 % and 1.2 %
      prevalence was found for physical, sensory and mental disability, respectively.
      CONCLUSIONS: Being disabled, added to that of being displaced, has become a
      public health problem as it affects a large group of individuals and families and
      also has a negative impact on society by affecting the productivity and
      development of human resources.

PMID- 17191604
TI  - [Adverse drug reactions in patients attending in emergency service].
AB  - OBJECTIVE: Describing adverse drug reactions (ADR) and analyzing the factors
      associated with their appearance in patients attending two hospitals' emergency
      services. METHODS: Descriptive, medicine-surveillance study of people consulting
      the emergency service at the Rosales hospital and the basic total health
      attention unit in Pereira, Colombia, between July and September 2005 for any
      symptom related to taking medicine. Naranjo's Adverse Drug Reaction probability
      scale was used. RESULTS: A total of 91 patients were found; 62,6 % were women
      having an average age of 36,3+/-22,4 (range 0-85). Antibiotics (24,2 %) NSAIDs
      (17,6 %), analgesics (9,9 %) and antidiabetic agents (8,8 %) were the most used
      drugs. 39,6 % of the patients only used one medicine; the average of drugs per
      patient was 2,4+/-1,5. Self-medication was present in 25,3 %. The most common
      ADRs arose from urticaria (31,9 %), hypoglycaemia (8,8 %), gastritis (6,6 %),
      angioedema (5,5 %) and anaphylaxis (4,4 %). 13,2 % of ADRs were serious and 54,9
      % were avoidable. 14,3 % of ADRs were classified as being definite and 75,8 %
      probable. Only 14,3 % of patients had a past history of ADR. The average cost of
      being attended was US$ 78,1 dollars. Analgesic use was associated with
      anaphylaxis, antibiotics with urticaria whilst NSAIDs was associated with
      gastritis and gastrointestinal bleeding, antidiabetic agents with hypoglycaemia,
      antipsychotic and antidepressants agents with neurological symptoms and warfarin
      with bleeding. CONCLUSIONS: The most important ADR-associated risk factors in
      patients attending emergency services were determined. Special care must be paid
      to patients using NSAIDs, warfarin, metoclopramide, metamizole, antipsychotic and
      antidepressants agents, antidiabetic agents and antibiotics, having a past
      history of ADR, being more than 55 years old and presenting urticaria, digestive
      and/or neurological symptoms

PMID- 17191605
TI  - [Adverse drug reactions in a Suba hospital of Bogota].
AB  - OBJECTIVE: This study was carried out in order to identify, document and assess
      suspect of Adverse Drug Reactions (ADR) that are report to pharmacovigilance
      program of Suba Hospital. METHODOLOGY: It was carried out an observational,
      descriptive and longitudinal study, in all the patients that consulted to the
      services of Urgencies and External Consultation, in the Hospital of Suba of the
      Bogota city. RESULTS: During the period of study 46 reports of suspicion of ADR
      were received, from those which 26 (56,6 %) corresponded to consultation reason,
      the 20 remaining it was indoor patient . In the classification for Organ-System,
      the gastrointestinal system presents the highest percentage of reports (30,4 %),
      followed by the cardiovascular (17,4 %), nervous central system (13 %), Skin (13
      %), Obstetric (10,9 %), renal system (4,3 %). The therapeutic Groups with more
      reported percentages of suspicion of ADR were Antipsychotic (30,4 %), Nutritional
      Supplements (17,4 %), Anti-infective (10,9 %), the other pharmacological groups
      present similar or inferior percentages to those mentioned previously. The
      incidence of ADR as consultation reason was 3 ADR consultation reason/10,000
      consultations / month. CONCLUSIONS: It was identify to pregnant, children and
      young people as a risk group to development an ADR. A low proportion it was
      clasificated as a serious and less than half as a possible according World Health
      Organization algoritm.

PMID- 17191603
TI  - [Resistance to cefepime in Enterobacter cloacae isolates from hospitals in
      Bogota, Colombia].
AB  - OBJECTIVE: The aim of this research was to detect the presence of genes encoding
      beta-lactamases which can confer cefepime resistance on Enterobacter cloacae
      isolates, meaning that this antibiotic may be considered an important therapeutic
      alternative. MATERIALS AND METHODS: 28 E. cloacae isolates collected from 4
      hospitals in Bogota during 2003 were analysed. Extended spectrum beta-lactamases
      and cephalosporinase production were phenotypically determined. The presence of
      extended spectrum beta-lactamase genes was determined by PCR amplification.
      Mating assays were done to determine the possible transfer of bla-genes encoding
      cefotaximases. RESULTS: Microbiological tests detected 57% of extended-spectrum
      beta-lactamase-producing isolates. blaTEM, blasHv and blacTX-M genes were
      detected by PCR in 82% of the isolates. 7 out of 9 isolates carrying group 1
      blacTX-M genes were in the resistant or intermediate range for cefepime. These
      isolates produced cefotaxime-resistant transconjugants. CONCLUSION: A
      relationship was found between resistance to cefepime and the presence of
      cefotaximases in E. cloacae. blacTx-M genes were present in 32% of the isolates,
      indicating an significant spread in the hospitals being studied. The facility of
      these genes' transfer between other species and Enterobacteria genera becomes an
      important reason for detecting them and controlling their spread in hospital
      settings. These results suggest a cautious use of cefepime for treating infection
      caused by E. cloacae strains which might produce CTX-M enzymes.

PMID- 17191606
TI  - [West Nile virus; ecology and epidemiology of an emerging pathogen in Colombia].
AB  - West Nile virus (WNV) has an enzootic mosquito-bird-mosquito cycle in nature,
      Culex sp mosquitoes being the main vectors. Birds are the main amplifying hosts.
      Humans and horses are incidental dead-end hosts. It produces a flu-like or a self
      limited febrile disease in most humans. It can cause encephalitis, meningitis or
      meningoencephalitis in cases of neurological disease, having greater incidence
      and mortality from encephalitis in older people and immune-compromised patients.
      Outbreaks have been reported in Africa, the Middle-east, Europe and Asia. WNV
      first appeared in North-America in 1999 and its circulation has been documented
      in Mexico, the Caiman islands, Jamaica, the Dominican Republic, Martinique,
      Guadalupe, Cuba, Puerto Rico, El Salvador and more recently in Colombia. The
      public health concern regarding WNV if it becomes introduced into Middle- and
      South-America will depend upon the interaction of several factors. The prevailing
      conditions in Colombia are apt for its spread and development. There are two main
      hypotheses; the virus could become enzootic and endemic and cause limited human
      disease, or it could become epidemic and cause annual outbreaks affecting large
      numbers of humans and animals. It will depend upon Colombian birds'
      susceptibility to the virus because of biological differences and intra-specific
      geographical variations in mosquitoe species' vector competence and the
      environmental effects on its ability to transmit the virus; such factors are
      determinant in the primary amplifying cycle.

PMID- 17191607
TI  - [Basic standards for Colombian paternity testing laboratories, 2005].
AB  - The Commission for Accreditation and Surveillance of Laboratories Practicing DNA
      Paternity Tests (created by the Colombian Law 721/2001) set up sub-commission to
      review the current basic Colombian standards required for paternity testing
      laboratories and make specific recommendations re the pertinent technical aspects
      in Colombia, taking ISO 17025 as current reference. This document contains such
      recommendations for Colombia.

PMID- 17191608
TI  - High-throughput methods of regulatory element discovery.
AB  - With the number of organisms whose genomes have been sequenced, a vast amount of
      information concerning the genetic structure of an organism's genome has been
      collected. However, effective experiment means to study how this information is
      accessed have only recently been developed. In this review, three basic methods
      for identifying regions of protein-DNA interaction will be introduced. The first
      two, chromatin immunoprecipitation (ChIP)-chip and ChIP-PET (for paired-end
      ditag), rely on the enrichment provided by chromosomal immunoprecipitation to
      interrogate the genomic sequence for the interaction sites of a protein of
      interest. In contrast, protein microarrays allow the identification of DNA
      binding protein that interacts with a DNA sequence of interest. These
      complementary methods of exploring protein-DNA interactions will increase our
      fundamental knowledge of how the information contained within the genome sequence
      is accessed and processed.

PMID- 17191609
TI  - Enhanced oligonucleotide microarray labeling and hybridization.

PMID- 17191610
TI  - Live-cell assay for simultaneous monitoring of expression and interaction of
      proteins.

PMID- 17191611
TI  - In vivo dual cross-linking for identification of indirect DNA-associated proteins
      by chromatin immunoprecipitation.

PMID- 17191612
TI  - Computer-assisted scoring of the elevated plus maze.

PMID- 17191613
TI  - Cell-targeted phagemid particles preparation using Escherichia coli bearing
      ligand-pIII encoding helper phage genome.

PMID- 17191614
TI  - Minimal T-DNA vectors suitable for agricultural deployment of transgenic plants.

PMID- 17191615
TI  - Modular and excisable molecular switch for the induction of gene expression by
      the yeast FLP recombinase.

PMID- 17191616
TI  - Method for detection and identification of multiple chromosomal integration sites
      in transgenic animals created with lentivirus.
AB  - Transgene delivery systems, particularly those involving retroviruses, often
      result in the integration of multiple copies of the transgene throughout the host
      genome. Since site-specific silencing of trangenes can occur; it becomes
      important to identify the number and chromosomal location of the multiple copies
      of the transgenes in order to correlate inheritance of the transgene at a
      particular chromosomal site with a specific and robust phenotype. Using a
      technique that combines restriction endonuclease digest and several rounds of PCR
      amplification followed by nucleotide sequencing, it is possible to identify
      multiple chromosomal integration sites in transgenic founder animals. By
      designing genotyping assays to detect each individual integration site in the
      offspring of these founders, the inheritance of transgenes integrated at specific
      chromosomal locations can be followed efficiently as the transgenes randomly
      segregate in subsequent generations. Phenotypic characteristics can then be
      correlated with inheritance of a transgene integrated at a particular chromosomal
      location to allow rational selection of breeding animals in order to establish
      the transgenic line.

PMID- 17191617
TI  - Facile approach for constructing TEV insertions to probe protein structure in
      vivo.
AB  - The tobacco etch virus (TEV) protease has been used as a tool to examine protein
      structure in vivo. TEV cleavage sites (TEVcs) have been introduced via cloning
      into unique restriction sites or random transposon mutagenesis. We describe a
      facile, efficient method for introducing TEVcs at precise locations in a gene to
      test specific predictions about protein structure. The method uses the lamda Red
      recombination system to construct seamless, in-frame insertions of the TEVcs at
      any desired location within an open reading frame (ORF). The system was tested
      using the multifunctional PutA protein Salmonella enterica sv. Typhimurium. The
      first step involved insertion of a chloramphenicol resistance (Cam(R)) cassette
      with a transcriptional terminator at the desired location. A second swap then
      replaces the Cam(R) insertion with the TEVcs. Placing a copy of the lac operon
      downstream of the putA gene provides a simple counterselection for replacement of
      the Cam(R) insertion and also provides a reporter gene for monitoring
      transcription of the mutated gene.

PMID- 17191618
TI  - Single-cell detection of microRNAs in developing vertebrate embryos after acute
      administration of a dual-fluorescence reporter/sensor plasmid.
AB  - The detection of microRNAs (miRNAs) at single-cell resolution is important for
      studying the role of these posttranscriptional regulators. Here, we use a dual
      fluorescent green fluorescent protein (GFP)-reporter/monomeric red fluorescent
      protein (mRFP)-sensor (DFRS) plasmid, injected into zebrafish blastomeres or
      electroporated into defined tissues of mouse embryos in utero or ex utero, to
      monitor the dynamics of specific miRNAs in individual live cells. This approach
      reveals, for example, that in the developing mouse central nervous system, miR
      124a is expressed not only in postmitotic neurons but also in neuronal progenitor
      cells. Collectively, our results demonstrate that acute administration of DFRS
      plasmids offers an alternative to previous in situ hybridization and transgenic
      approaches and allows the monitoring of miRNA appearance and disappearance in
      defined cell lineages during vertebrate development.

PMID- 17191619
TI  - Rapid and quantitative method of allele-specific DNA methylation analysis.
AB  - Several biological phenomena depend on differential methylation of chromosomal
      strands. While understanding the role of these processes requires information on
      allele-specific methylation, the available methodologies are not quantitative or
      labor-intensive. We describe a novel, rapid method to quantitate allele-specific
      DNA methylation based on the combination of bisulfite PCR and Pyrosequencing. In
      this method, DNA is first treated with sodium bisulfite, which converts cytosine
      but not 5-methylcytosine to uracil. Genes of interest are subsequently amplified
      using PCR. Allele-specific methylation can then be determined by pyrosequencing
      each allele individually using sequencing primers that incorporate single
      nucleotide polymorphisms (SNPs) that allow differentiation between the two
      parental alleles. This allele-specific methylation methodology can potentially
      afford quantitative analyses relevant to the regulation of X chromosome
      inactivation, allele-specific expression of genes in the immune system,
      repetitive elements, and genomic imprinting. As an illustration of our new
      method, we quantitated allele-specific methylation of the differentially
      methylated region of the H19 gene, which is imprinted. Although we could reliably
      determine allele-specific methylation with our technique, additional studies will
      be required to confirm the ability of our assay to measure loss of imprinting.

PMID- 17191620
TI  - Full developmental potential of mammalian preimplantation embryos is maintained
      after imaging using a spinning-disk confocal microscope.
AB  - Fluorescent live imaging of cells and embryos at subcellular resolution poses
      significant challenges for biologists due to morbidity and mortality ensuing from
      phototoxicity. Here we report the use of a spinning-disk confocal microscope to
      image mouse and bovine preimplantation embryos without impairing their
      developmental potential. We also present data indicating that this imaging
      technique does not affect the functionality of subcellular components as assessed
      by reactive oxygen species (ROS) production, caspase activity, and DNA integrity.
      Spinning-disk confocal microscopy was also useful in determining cell number and
      allocation in transgenic bovine blastocysts. We conclude that this imaging method
      is suitable for monitoring preimplantation embryos.

PMID- 17191621
TI  - When will we ever learn?

PMID- 17191622
TI  - Deadly addiction: India and Pakistan on the nuclear brink.
AB  - The effects of nuclear weapons on Hiroshima and Nagasaki and the political and
      moral context surrounding their use are discussed. The rationale for development
      of the Indian and Pakistani nuclear weapons programmes are summarised and
      critically examined in comparison to the costs of the programmes and the social
      needs, which could have been addressed. Alternative routes to provide peace and
      security are proposed, both for India, Pakistan, and other nuclear-weapon states,
      with particular emphasis on the role of physicians and other health workers.

PMID- 17191623
TI  - Korean atomic bomb survivors' report on the present status and health of their
      children: a mail questionnaire survey.
AB  - A mail questionnaire survey on the present status and health of children of
      Korean survivors of the 1945 atomic bombing of Japan was conducted in 2004. In
      total, 1,115 Korean A-bomb survivors' reports on demographic factors and the
      health of their children (n = 4,079) were analysed. In 2004, 293 of their
      children were reported to have died and 3,786 children still living. Among the
      deceased children, the cause of death was unidentified in 64 per cent of cases.
      The most frequently reported cause of death was infectious disease (9.6%). Most
      of the deaths (51%) were reported to have occurred in children less than ten
      years old. The most frequently reported congenital disorders among living
      children were mental retardation (0.18%) and congenital bone disorders (0.18%).
      Further study and administrative support are needed to more accurately determine
      the status of Korean A-bomb survivors and their children.

PMID- 17191624
TI  - Skin injuries caused by new riot control agent used against civilians on the West
      Bank.
AB  - A new riot control agent, used by the Israeli army against civilians protesting
      about the Separation Wall on the West Bank, has been reported as causing severe
      skin injuries. We obtained one of the munitions and have identified the contents
      as capsaicin with an inert carrier and a dispersal agent. This corresponds to the
      commercially available 'Pepperball Tactical Powder'. Skin injuries of the
      severity described have not previously been reported with this agent, and would
      be difficult to manage for clinicians who were unaware of the nature of the
      agent.

PMID- 17191625
TI  - Medical education and health care in Iraqi Kurdistan in the last four decades.
AB  - Medical education and health care in Iraqi Kurdistan were oppressed by the regime
      of Saddam Hussein for four decades. There have been efforts to revive them by
      Kurdish and non-Kurdish professionals in and outside Kurdistan with the
      assistance of various governmental and non-governmental organisations. However,
      the health care and medical education systems in Iraqi Kurdistan require ongoing
      international support. Recent global awareness of the war on terror and attempts
      to rebuild the health care system should not concentrate only on the immediate
      effects of the war, but they should also focus on the wide-ranging implications
      of the previous dictatorship regime.

PMID- 17191626
TI  - Chernobyl--looking back to go forwards: the September 2005 IAEA Conference.

PMID- 17191627
TI  - Chernobyl: the true health and environmental legacy.

PMID- 17191628
TI  - A commitment to peace: a doctor's tale.

PMID- 17191629
TI  - The history of the Crown Court at the Middlesex Guildhall.

PMID- 17191630
TI  - Tsunami disaster victim identification in Sri Lanka: legal aspects.
AB  - Natural hazards amounting to disasters have almost become an endemic phenomenon
      during past decades throughout the globe, particularly affecting less resourced
      countries. The capabilities of the affected nations are stretched to the maximum
      in most of the disasters, thereby exposing deficiencies at various levels of the
      disaster mitigation mechanisms. A key factor identified through the human
      experience of all previous disaster scenarios is the requisite of effective and
      integrated local, national and regional disaster management mechanisms. The
      national and regional legal framework in this context can supplement disaster
      management enormously by drafting and implementing practical legislation which
      can be activated in disaster situations to co-ordinate the relief missions and
      minimize the damage. Thus, the existing legal systems and legislation at national
      and regional levels should be modified accordingly to yield proper disaster
      management policies. However, many less resourced countries are still lacking
      functional disaster management mechanisms in local legislation and are
      consequently highly vulnerable to heavy casualties in disasters. Sri Lanka is a
      typical example of a state which had an ineffective disaster management
      mechanism, not strengthened by legislation, when the Asian tsunami struck the
      country in December 2004, despite having frequently been affected by natural and
      man-made hazards during the past three decades. The net effect was total disarray
      in disaster victim identification, leading to drastic and irreparable
      consequences.

PMID- 17191631
TI  - Euthanasia and assisted suicide: comparison of legal aspects in Switzerland and
      other countries.
AB  - The purpose of this paper is to present the legal aspects associated with
      assisted suicide in Switzerland and compare them with those in other countries.
      Like euthanasia, assisted suicide is a subject that induces much discussion in
      many countries. While the law is very liberal in some countries, such as Belgium
      and the Netherlands (where both euthanasia and assisted suicide take place),
      these practices are very controversial in other countries, such as France, where
      they remain taboo subjects. In the United States of America, the laws concerning
      assisted suicide can differ greatly from one state to another. For example, in
      Oregon, assisted suicide is allowed if applied by a medical doctor; in others,
      this act is illegal. In Canada, it is punishable according to the Criminal Code.
      In Switzerland euthanasia is punishable by law. However, the penal code does not
      condemn assisted suicide, whether carried out by a medical doctor or another
      person, provided it is not carried out through selfish motives. The application
      of these practices has become simplified in recent years and societies for the
      right to die with dignity based on this principle have come into being (Exit and
      Dignitas). In the French- and German-speaking parts of Switzerland the
      association Exit assists individuals living in Switzerland with serious
      progressive and incurable disease in their engagement to end their life. The
      association Dignitas, in the German-speaking part of Switzerland, also undertakes
      -in the same circumstances--to assist individuals coming from foreign countries.
      Dignitas welcomes several such individuals every year, especially from Germany,
      where a similar approach does not currently exist.

PMID- 17191632
TI  - Arson: a growing inferno.
AB  - In a series of 34 arsonists, our survey compares the changing trends in arson to
      an earlier study carried out ten years ago in the same region in the UK by Rix
      (1994). The survey is based on pre-trial court reports done by the second author
      only. Fire-setting offending was predominantly seen in the young male (18-32).
      Fire-setting started as early as age seven and was seen as late as 63 years of
      age. More than half of the subjects received some form of family support. At
      least one third had an ICD-10 (WHO, 1992) diagnosable mental disorder and more
      than half were diagnosed with a psychiatric disorder during the time of
      reporting. A third of the subjects had a personality disorder diagnosis prior to
      reporting and another third had disordered personality traits established during
      the time of reporting. More than half had a psychological motive. Eleven per cent
      started a fire for excitement with only one for revenge. A third of the subjects
      were first time arsonists. Sixty-five per cent of arson involved building damage
      and all the 34 subjects were under the influence of alcohol prior to and during
      the act of arson. Additionally, there was cannabis use in nearly half of the
      subjects. Opioids and poly substance abuse were seen in a third of subjects. With
      the extent of financial and social burden along with risks, attention should be
      focused on accessing these individuals early to preventing recidivism. More
      research needs to be undertaken to identify the psychological motives behind fire
      setting and to look into the drugs and alcohol problems amongst the younger age
      groups.

PMID- 17191633
TI  - Paediatric deaths in Kuala Lumpur.
AB  - The main aim of this study was to determine the causes and epidemiological
      aspects of paediatric death. Data was collected on 143 cases of paediatric death
      from a total of 2,895 autopsies performed in University Malaya Medical Centre
      (UMMC), Kuala Lumpur, over a five-year period from 2000 to 2004. There were 78
      males and 65 females. The largest number of cases (32.9%) were stillborn. The
      highest proportion of cases (30.1%) were Chinese. The majority of cases of
      paediatric death were non-traumatic (74.8%) of which intrauterine death (IUD) was
      the most common (32.9%). Amongst the traumatic deaths (25.2%), accidental injury
      (23.8%) was observed in the majority of cases.

PMID- 17191635
TI  - Outcome of referral to a prison mental health team.
AB  - This retrospective case note study describes the demographic, offence and
      diagnostic characteristics of 115 referrals made to a psychiatric service within
      HMP Perth between May 2003 and April 2004. Twenty per cent of referrals were
      diagnosed with a major mental illness with remand prisoners having a higher
      overall prevalence. Nearly 70% had previous contact with psychiatric services, a
      similar percentage had previous substance misuse. Over 8% were transferred out of
      prison and over a quarter continued to be followed up at the end of the study
      period. A wide range of index offences was seen. Over two-thirds had a previous
      history of offending and nearly 60% had a previous custodial sentence, reflecting
      a high degree of recidivism. This study supports the high degree of psychiatric
      morbidity in the prison population shown in other studies. The role of a prison
      psychiatric service is discussed in the context of services to mentally
      disordered offenders.

PMID- 17191634
TI  - The use of histology in 638 coronial post-mortem examinations of adults: an
      audit.
AB  - An audit was performed to determine the effectiveness of histological sampling of
      forensic post-mortem cases based on a review of three years' data, which
      comprised 638 adult autopsy cases. During the study period organs and tissues
      that appeared macroscopically normal and abnormal were extensively sampled.
      Histology was regarded as in some way contributory (providing, altering or
      confirming a cause of death) 53% of the time. The use of histology provided the
      cause of death in 49 (24%) of the 203 cases not given a cause of death after the
      completion of the macroscopic examination. When an interim cause of death had
      been supplied following the completion of the gross examination it was changed in
      4.8% of cases, but there were no changes of the manner of death. The majority of
      the histological diagnoses or discrepancies involved the lungs and the heart. All
      diagnoses relevant to determining the cause of death would have been made if
      samples had been taken only from the left ventricle, right ventricle, coronary
      arteries, lungs, kidneys and brain with any tissue or organ that appeared
      abnormal macroscopically. A macroscopically identified abnormality that appeared
      to have been responsible for death was not sampled in 20 cases; consequently,
      more attention will be paid to sampling macroscopically abnormal tissues. As a
      result of this audit histology sampling practice has been revised and will be re
      audited in the future.

PMID- 17191636
TI  - The court medical expert in France: changes in status.
AB  - In France the status of the court expert has undergone a significant change with
      the adoption of statute no. 2004-130 of 11 February 2004 and its implementing
      regulations no. 2004-1463 of 23 December 2004. This article looks at the two most
      outstanding aspects of this change in status: (i) the conditions for registering
      on a court of appeal list and, (ii) the practical details of the quality control
      of the court expert's work as exercised by the judge. The article concludes with
      a brief comparison with the expert witness situation in England and Wales.

PMID- 17191637
TI  - Pattern of injuries in fatal falls from buildings.
AB  - When bodies are brought for autopsy it is sometimes unclear whether the injuries
      are due to a fall from a height or due to blunt trauma from other causes,
      especially when the bodies are found near buildings with no eyewitnesses
      available. Studies discussing the injury patterns in adults after falls
      exclusively from buildings are rare. A five-year retrospective study was carried
      out on 151 cases of fatal falls from buildings brought for autopsy. The aim was
      to assess the pattern of these injuries and identify features helpful in
      discriminating between these and injuries due to blunt trauma from other causes.
      The majority of cases comprised subjects who fell from heights of 10-20 feet (3
      6m) with most falls occurring late at night or in the early morning. The pattern
      that emerged is quite distinct from ground level falls and pedestrian injuries.
      Abrasions are the commonest injury and bruises very rare. Lacerations are mostly
      on the head and skull fractures are evenly distributed between the vertex, base
      and vertex plus base. Subarachnoid haemorrhage is the commonest intracranial
      lesion. Extradural haemorrhage alone is rare. Fractures of ribs and cervical
      vertebrae are common and fractures of thoracic vertebrae and long bones are
      uncommon. Safety measures to prevent such falls have been suggested.

PMID- 17191638
TI  - Industrial accidental deaths in the Niger delta region of Nigeria: a study of 32
      autopsies in Port Harcourt.
AB  - Accidents in the oil industry in the Niger delta region of Nigera raise concerns
      about safety measures and the management of industrial sites. A total of 32
      autopsies were performed after coroners' inquest forms were served on the authors
      by the State, which serve as consent and request. Standard procedures were
      adopted in all the cases and the reports were appropriately issued. Death from
      industrial accidents accounted for 2.5% and 6.1% of total autopsies and
      accidental death autopsies respectively. The youngest victim was a 19 year old
      male while the oldest was a 55 year old male. The age group 30-39 years was the
      most vulnerable. There was a male dominance; (male:female ratio = 9.7:1). The
      commonest accidents in their order of frequency were: falling from a height,
      explosion/fire, motor vehicle accidents and falling objects. Multiple injuries,
      head and neck trauma and drowning were the commonest cause of death at autopsy.
      Accidental deaths were commoner in the small-scale industries (81%) than in the
      large-scale industries (19%). This is the first time such a study has been
      carried out locally. The proportion of accidental deaths in the small scale
      industries relative to that of the large ones may be attributed to the poor
      enforcement of safety measures in the smaller industries

PMID- 17191639
TI  - Death due to railway-related suicidal decapitation: a case report.
AB  - In Italy, railway-related deaths give rise to extensive inquiries because it is
      mandatory for the public prosecutor to investigate the circumstances of death.
      For the railway embankment, normal traffic rules are not valid and the guilt of
      the engine driver usually cannot be proven. Consequently, these cases are very
      often declared as suicides without adequate evidence. Furthermore, there is a
      potential risk of confusion with homicide, body dismemberment or mutilation. Our
      medico-legal institutes are increasingly engaged with expert opinions on
      questions of accident, suicide or homicide because they lead to complications in
      the fields of insurance, criminal and civil law.

PMID- 17191640
TI  - Artificial penile nodules--a forensic pathosociology perspective: four case
      reports.
AB  - The article reports on four cases of penile modifications, known in medico-social
      literature as artificial penile nodules, observed during the external coronial
      autopsy examinations of three males of Southeast Asian origin, admitted over a
      five-week period, and a Australian youth admitted 30 months previously as a death
      in custody. Fang muk, bulletus, chagan balls, tancho balls, and penis marbles are
      terms synonymous with the ethno-sexual practices of various sub-cultural groups
      of South-east Asian males, the terminology being specific to the geographic
      region. It describes the implanting of firm spherical foreign objects, in the
      form of beads, in the subcutaneous tissue of the shaft of the penis proximal to
      the glans to allegedly enhance the sexual pleasure of females during sexual
      intercourse. Non-Asian nationalities such as Romanians (Wolf and Kerl, 1991),
      Russians (Serour, 1993) Fijians (Scott and Norton, 1993) and Middle Eastern males
      have also adopted this practice within sub-cultural groups of society. The
      article provides a brief historical account and the social, motivational, and
      occupational characteristics of individuals adopting this sexual practice and the
      surgical and health side effects of the implantation of artificial penile
      nodules, relating these aspects to the forensic cases observed.

PMID- 17191643
TI  - Practical oral sedation.

PMID- 17191641
TI  - Female autoerotic deaths--still often overlooked: a case report.
AB  - Female autoerotic deaths are less common than male ones and usually present in a
      less obvious way. Thus, such deaths can be easily overlooked, even by senior
      investigators, if the latter are not fully aware of the particularities of female
      autoerotic cases. We present the case of a 34-year-old woman, found dead in her
      apartment, with several foreign body insertions and a dog leash around the neck.
      Despite the great experience of the investigative team, autoerotic death was not
      considered at first. This case illustrates the importance of forensic teams
      having knowledge of the particularities of female autoerotic deaths.

PMID- 17191644
TI  - Practical oral sedation.

PMID- 17191645
TI  - Is federal funding for dental research in jeopardy?

PMID- 17191646
TI  - A report from the American Academy of Periodontology. Guidelines for the
      management of patients with periodontal diseases.

PMID- 17191647
TI  - Q and A with Dr Mike Rethman.

PMID- 17191648
TI  - Maxillary sinus augmentation: evidence-based decision making with a biological
      surgical approach.
AB  - Sinus elevation surgery has been used by the dental profession to increase bone
      quantity in the posterior maxilla for the placement of root-form implants. The
      original treatment protocol was developed using existing bone-healing theories
      that relied on expert opinion. In 2003 and 2004, 2 evidence-based literature
      reviews were published, expanding significantly on the previous review of 1996.
      The new reviews were based on the best studies available and were designed to
      present information that would help clinicians achieve more favorable outcomes.
      This article discusses this information and answers further questions relating to
      the sinus elevation procedure.

PMID- 17191649
TI  - A new era in periodontal and periimplant regeneration: use of growth-factor
      enhanced matrices incorporating rhPDGF.
AB  - A new, powerful off-the-shelf wound healing and bone regeneration technology
      termed growth-factor enhanced matrix (GEM) has recently become available for
      clinical use. This graft material consists of a concentrated solution of pure
      recombinant human platelet-derived growth factor (rhPDGF-BB), the synthetic form
      of the body's key natural wound healing stimulator PDGF-BB, and an
      osteoconductive (bone scaffold) matrix. This is the first available purified,
      recombinant (synthetic) growth factor product and is the result of over a decade
      of extensive research. Clinical and animal study results with this graft material
      demonstrate that it is capable of simultaneously promoting wound healing,
      regeneration of bone, and acceleration of gingival attach-plent gain in
      challenging periodontal and periimplant defects.

PMID- 17191650
TI  - A tempest in a teapot.

PMID- 17191651
TI  - OSAP'S safety and infection control report card.

PMID- 17191652
TI  - Army dental research?

PMID- 17191653
TI  - Protecting yourself!

PMID- 17191655
TI  - Collection strategies: it's how you say what you say.

PMID- 17191656
TI  - HIV, needlestick: free information for dental workers.

PMID- 17191658
TI  - Myocardial oxygen consumption regulation in isolated mouse heart: assessment by
      intracoronary administration of exogenous nitric oxide.
AB  - In our previous work we have shown that in mouse heart basal level of endothelial
      produced nitrite, as a marker of nitric oxide (NO) formation, was 9.7 nmol l(-1).
      Bradykinin (10 microl l(-1)) induced a 5-fold rise in nitrite release, the
      coronary venous effluent concentration being 58 nmol l(-1), but there was no
      effect on myocardial oxygen consumption (MVO2). The aim of this study was to
      assess the levels of authentic nitric oxide solution, exogenously applied, on
      myocardial oxygen consumption. Isolated mouse hearts (n=36) were paced (500
      imp./min) and perfused at constant flow (16.0 +/- 0.3 ml g(-1) min(-1)). When
      coronary vasculature resistance was carefully controlled by adenosine (1 micromol
      l(-1)), authentic nitric oxide solution, in a concentration less than 5 micromol
      l(-1) did not alter myocardial oxygen consumption. Only concentrations of nitric
      oxide higher than 5 micromol l(-1) induced reduction in myocardial oxygen
      consumption. Thus in the saline perfused mouse heart, with carefully controlled
      vasodilatation, modulating myocardial nitric oxide levels using an arterial
      application of authentic nitric oxide, concentrations higher than 5 micromol l(
      1) of nitric oxide were required to induce a decrease in myocardial oxygen
      consumption.

PMID- 17191657
TI  - The effects of nimodipine and L-NAME on coronary flow and oxidative stress
      parameters in isolated rat heart.
AB  - The aim of this study was to assess the effects of Ca2+ channel antagonist
      nimodipine (in concentration which competitive inhibited phosphodiesterase 1-
      PDE1) on oxidative stress alone or under inhibition of nitric oxide synthase by L
      NAME in isolated rat heart. The hearts from male Wistar albino rats (n=18, BM
      about 200 g, age 8 weeks) were retrograde perfused according to the Langendorff
      technique at gradually increased constant perfusion pressure conditions (CPP, 40
      120 cm H2O). The experiments were performed under control conditions, in the
      presence of Nimodipine (2 microM) or Nimodipine (2 microM) plus L-NAME (30
      microM). Coronary flow (CF) varied in the autoregulatory range from 3.7 +/- 0.4
      ml/min/g wt at 50 cm H2O to 4.35 +/- 0.79 at 90 cm H2O. Basal nitrite outflow,
      index of lipid peroxidation (measured as TBARS release) and superoxide anion
      release (O2-) (at 60 cm H2O) were 0.64 +/- 0.18 nmol/min/g wt, 0.55 +/- 0.13
      micromol/min/g wt and 19.72 +/- 3.70 nmol/min/g wt, respectively. Nimodipine
      induced significant vasodilation at all values of CPP (from 26% at 40 cm H2O to
      36% at 120 cm H2O) accompanied with significant decrease of nitrite outflow (from
      59% at 40 cm H2O to 40% at 120 cm H2O), significant increase of TBARS above
      autoregulatory range (about 40%) and significant increase of O2- release (from
      186% at 40 cm H2O to 117% at 120 cm H2O). However, perfusion with L-NAME
      completely reversed the effects of Nimodipine. Nimodipine-induced flow changes
      were decreased under L-NAME (from 3% at 40 cm H2O to 11% at 120 cm H2O) without
      changes in the autoregulatory range, accompanied with significantly increased
      nitrite outflow (from 69% at 40 cm H2O to 36% at 120 cm H2O) and TBARS release
      (almost 50%), as well as significantly decreased O2- release (from 50% at 40 cm
      H2O to 43% at 120 cm H20). Our findings show that effect of nimodipine on
      coronary flow should be significantly influenced by NO, TBARS and O2- release in
      isolated rat heart.

PMID- 17191659
TI  - Effect of L-arginine on the relaxation caused by sodium nitroprusside on isolated
      rat renal artery.
AB  - In the present study we investigated the mechanism of nitric oxide induced
      relaxation of renal arteries, with or without endothelium, taken from
      normotensive and spontaneously hypertensive (SH) rats. With this purpose in mind,
      the effects of the nitric oxide donor, sodium nitroprusside (SNP), with and
      without L-arg in the medium, on isolated rat renal artery relaxation were
      studied. Relaxing effect of SNP was higher in normotensive (10(-5) M of SNP
      caused 220% of relaxation in the cases with endothelium and 240% without
      endothelium), in comparison with SH rats (100% of relaxation with endothelium and
      150% without). L-arg antagonized the relaxing effect of SNP in the examined renal
      arteries, more in normotensive (100-160% with endothelium and 110-195% without)
      than in hypertensive ones (0-10% with endothelium and 35-75% without) at SNP
      concentrations 10(-7) - 10(-5) M, respectively (*P < 0.05; **P < 0.001). L-arg
      did not significantly change relaxing effect of SNP in the isolated renal
      arteries with endothelium taken from SH rats, which show that L-arg, by modifying
      the chemical versatility of NO into redox active forms -nitrosonium (NO+) and 
      nitroxyl (NO-), produces different relaxing effects in normotensive and
      hypertensive isolated arteries of rats, with or without endothelium, potentiating
      the role of nitroxyl induced relaxation in SH rats.

PMID- 17191660
TI  - The effects of iron-containing superoxide dismutases on haemodynamic parameters
      in spontaneously hypertensive rats.
AB  - The product of FeSOD activity is hydrogen peroxide (H2O2). Furthermore, FeSOD can
      modify the chemical versatility of NO into its redox-active forms: nitrosonium
      cation (NO+) and nitroxyl anion (NO-). All of these low molecular weight species
      are vasoactive and, in particular, NO- induces calcitonin gene-related peptide
      (CGRP) synthesis (known to be the most potent relaxation-promoting peptide). In
      this study the effects of bolus infusions of iron-containing superoxide dismutase
      (FeSOD) and of superoxide dismutase containing both iron and manganese (FeMnSOD)
      on the arterial blood pressure (MAP), the arterial blood pressure (CO) and the
      total vascular resistance (TVR) in spontaneously hypertensive (SH) rats were
      determined. Bolus infusion of FeSOD induced a biphasic response in the MAP (an
      initial increase was followed by a significant decrease). At the end of the
      experiment the MAP returned to its basal value. FeMnSOD (the enzymatically
      inactive form of FeSOD) had no effect on the MAP in these experiments. Bolus
      infusions of FeSOD and of FeMnSOD had no effect either on the both the CO or on
      the TVR in SH rats. Our results indicate that arterial relaxation changes
      mediated by NO- may be important for regulation of blood pressure in SH rats.

PMID- 17191661
TI  - Mechanism of 3-deazaguanine transport in the rat heart.
AB  - The aim of this study was to determine the mechanism of transport of 3
      deazaguanine in the rat heart. We used single-pass, paired-tracer dilution method
      on isolated and retrogradely perfused rat hearts. The maximal cellular uptake
      (Umax) and total cellular uptake (Utot) of 3-deazaguanine were determined under
      control conditions and under influence of possible modifiers. Both Umax and Utot
      were significantly reduced in the presence of unlabeled 3-deazaguanine (from
      19.57 +/- 2.02% to 8.14 +/- 1.19% and from 16.49 +/- 3.65% to 4.70 +/- 1.96%,
      n=6, respectively). The presence of pyrimidine nucleoside thymidine caused the
      reduction of both Umax and Utot (from 20.03 +/- 3.76% to 13.58 +/- 3.16% and from
      16.43 +/- 3.58% to 11.94 +/- 3.13%, n=6, respectively). Also, we tested the
      effect of the absence of sodium ions in perfusion solution (both Umax and Utot,
      significantly reduced from 17.95 +/- 2.73% to 16.67 +/- 2.16% and from 16.68 +/-
      2.97% to 14.81 +/- 3.04%, n=6, respectively) and the effect of dinitrophenol
      (both Umax and Utot significantly reduced from 19.09 +/- 3.68% to 10.58 +/- 3.14%
      and from 16.86 +/- 3.84% to 7.10 +/- 3.11%, n=6, respectively). The results of
      self- and cross-inhibition studies show that the transport of 3-deazaguanine is
      saturable, energy- and sodium-dependent and that 3-deazaguanine uses endogenous
      transport systems for thymidine and adenosine for its own transport.

PMID- 17191662
TI  - Valproate and delta-sleep peptide display high efficacy against metaphit-induced
      audiogenic seizure in rats.
AB  - The effects of valproate (VPA) and delta sleep-inducing peptide (DSIP) on
      metaphit-induced generalized, audiogenic seizure in adult rat males were
      compared. The animals were i.p. injected with: (1) Saline; (2) metaphit (mp, 10
      mg kg(-1)); 3. metaphit (10 mg kg(-1)) and 8 h later with DSIP (0.1, 0.2, 0.4 or
      1.0 mg kg(-1)), 4. metaphit (10 mg kg(-1)) and 8 h later with VPA (50, 75 or 100
      mg kg(-1)); 5. DSIP alone (1.0 mg kg(-1)) and 6. VPA, alone (100 mg kg(-1)). The
      rats were exposed to sound stimulation at hourly intervals and the behavior and
      EEG were analyzed. The EEG signals in metaphit rats appeared as a sleep-like
      pattern and spike-wave complexes with increased power spectra. Valproate and DSIP
      reduced the incidence of seizure and prolonged duration of latency in a dose
      dependent manner. ED50 of valproate in the 1st hour after administration was
      63.19 mg kg(-1) and that of DSIP 3.19 mg kg(-1) four hours after injection. This
      suggests that VPA, reached a peak of action immediately after the application,
      while DSIP had a prolonged action, mildly reducing, but not abolishing metaphit
      seizure. None of the applied VPA and DSIP doses eliminated the metaphit-provoked
      EEG signs of epileptiform activity.

PMID- 17191664
TI  - In vitro assay for the quantitative measurement of apoptotic lymphocytes
      phagocytosis by peripheral blood monocytes.
AB  - Currently used assays for the quantification of apoptotic cells uptake by
      phagocytes have several methodological problems. Our assay overcomes some of
      these problems. As a source of apoptotic cells we used peripheral blood
      lymphocytes obtained from the patients with chronic lymphoblast leukaemia.
      Apoptosis was induced by incubating cells with cycloheximide for up to 24 h. The
      assay was performed in suspension of peripheral blood mononuclear cells. For the
      visualisation of the phagocytes and phagocyted cells and discrimination of
      phagocyted from bound apoptotic cells we used Acridine orange/Ethidium bromide
      double staining. Here we offer a simple test which enables reliable measurement
      and it can show the difference of phagocytic potential between different
      individuals.

PMID- 17191663
TI  - Oxidative stress in the rats brain capillaries in sepsis--the influence of 7
      nitroindazole.
AB  - As a part of blood-brain barrier, brain capillaries participate in
      pathophysiological events during systemic inflammation. We investigated the
      effects of 7-nitroindazole (7-NI), selective neuronal nitric oxide synthase (NOS)
      inhibitor, to oxidative status (OS) of brain capillaries. Adult Wistar rats were
      randomized at groups: control group (CG) (sham operated), sepsis group (GS)
      (cecal ligation and perforation with inoculation of Escherichia coli (ATCC
      25922), 7-NI group (G7-NI), (30 mg/kg b/w i.p.) and 7-NI + sepsis group (G7-NIS),
      (7-NI was applied 30 minutes before operation). Lipid peroxidation index (LPI),
      nitrite concentration, superoxide dismutase (SOD) activity and superoxide anion
      (O2*-) content were determined 3, 6, 24 and 48 hour in each group. Cerebral
      capillaries were separated from non-vascular brain tissue using sucrose gradient.
      Compared to controls, LPI, nitrite and O2*- increased at SG. In the G7-NIS, LPI
      reached control values at the 24th and 48th hour, while nitrite were decreased at
      the 3rd and 24th hour, compared to controls. In the same group, O2*- decreased at
      the 3rd, 6th and 24th hour, although SOD showed variable activity. The systematic
      nNOS inhibition with 7-NI forces OS on early terms of sepsis, but lately it
      contributes to the normalization of OS in cerebral capillaries.

PMID- 17191665
TI  - The anti-oxidative defence system in the isolated rat uterus during spontaneous
      rhythmic activity.
AB  - Possible interactions between nitric oxide donors, reactive oxygen species and
      anti-oxidative defence enzymes led us to determine the activities of anti
      oxidative defence enzymes in isolated uterine smooth muscle before and after
      spontaneous rhythmic activity ex vivo. For our experiments we used isolated uteri
      from female Wistar rats. Our results showed an increase in total superoxide
      dismutase (SOD) and Mn SOD activities in uterine smooth muscle after spontaneous
      contractions when compared with nonexercised uterine smooth muscle. The activity
      of catalase (CAT) and glutathione preoxidase (GSH-Px) were also increased. No
      statistically significant changes in the activities of glutathione reductase (GR)
      and CuZn SOD were found. It is known that an organism's anti-oxidative defence
      system (guarding against excessive reactive oxygen species generation) requires
      balanced increments in its individual anti-oxidative enzyme activities rather
      than increases in the activity of only some enzymes without increases in others.
      Thus, we may conclude that some adaptive responses are found in exercised uterine
      smooth muscle but are not complete. Therefore, our results indicate that changes
      in anti-oxidative enzyme activities may influence the results of the examination
      of substances ex vivo.

PMID- 17191666
TI  - Regional differences in antioxidative response of rat brain after cranial
      irradiation.
AB  - In order to examine if differences in activity and inducibility of antioxidative
      enzymes in rat cerebral cortex and hippocampus are underlying their different
      sensitivity to radiation, we exposed four-day-old female Wistar rats to cranial
      radiation of 3 Gy of gamma-rays. After isolation of hippocampus and cortex 1 h or
      24 h following exposure, activities of copper-zinc superoxide dismutase
      (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT) were
      measured and compared to unirradiated controls. MnSOD protein levels were
      determined by SDS-PAGE electrophoresis and Western blot analysis. Our results
      showed that CuZnSOD activity in hippocampus and cortex was significantly
      decreased 1 h and 24 h after irradiation with 3 Gy of gamma-rays. MnSOD activity
      in both brain regions was also decreased 1 h after irradiation. 24 h following
      exposure, manganese SOD activity in hippocampus almost achieved control values,
      while in cortex it significantly exceeded the activity of the relevant controls.
      CAT activity in hippocampus and cortex remained stable 1 h, as well as 24 h after
      irradiation with 3 Gy of gamma-rays. MnSOD protein level in hippocampus and
      cortex decreased 1 h after irradiation with 3 Gy of gamma-rays. 24 h after
      exposure, MnSOD protein level in cortex was similar to control values, while in
      hippocampus it was still significantly decreased. We have concluded that regional
      differences in MnSOD radioinducibility are regulated at the level of protein
      synthesis, and that they represent one of the main reasons for region-specific
      radiosensitivity of the brain.

PMID- 17191667
TI  - Iodide excess exerts oxidative stress in some target tissues of the thyroid
      hormones.
AB  - Environmental iodine deficiency continues to be a significant public health
      problem worldwide. On the other hand, iodide excess results principally from the
      use of iodine-containing medicinal preparations or radiographic contrast media.
      For this reason we intended to explore iodide excess impairment on
      prooxidant/antioxidant balance of the thyroid gland, hepatic tissue and in blood
      and the effect of selenium administration on oxidative stress markers under the
      same circumstances. Experiments were performed for 10 days with white, male,
      Wistar rats, as follows: group 1: control-normal iodine supply group; 2: high
      iodine diet, group; 3: high iodine diet and selenium; group 4: high iodine diet
      and Carbimasole. Oxidative stress markers such as lipid peroxides were determined
      in thyroid gland, hepatic tissue and in blood. Measuring H+ donor ability of the
      sera and catalase activity in thyroid gland and in hepatic tissue assessed
      antioxidant defense. Iodide excess had prooxidant effects, leading to an
      increased lipid peroxides level and catalase activity in target tissues and in
      blood and to a decreased H+ donor ability of the sera. Selenium supplementation
      had opposite effects. Present data allow us to conclude that the alterations due
      to iodide excess in thyroid gland, hepatic tissue and in blood are mediated
      through oxidative stress.

PMID- 17191668
TI  - The influence of laparoscopic and open surgery on the concentration and
      structural modifications of insulin-like growth factor binding protein 3 in the
      human circulation.
AB  - Insulin-like growth factor binding protein 3 (IGFBP-3) is the most abundant
      insulin-like growth factor binding protein in the circulation. The aim of the
      present work was to investigate the influence of surgery (laparoscopy and open)
      on the concentration and carbohydrate content of IGFBP-3. The concentration of
      IGFBP-3 was measured using an immunoradiometric assay (IRMA), its protein profile
      was characterised using immunoblotting and its sialic acid content was examined
      by means of Sambucus nigra agglutinin (SNA) affinity chromatography. The
      concentration of IGFBP-3 was significantly (p < 0.001) lower in preoperative
      patients compared with healthy subjects. Only patients that underwent open
      surgery showed a further significant decrease in the concentration of IGFBP-3.
      Immunoblotting detected two intact IGFBP-3 isoforms, as well as proteolytic
      fragments. SNA-affinity chromatography showed that in patients that underwent
      surgery the ratio between the two IGFBP-3 glycoforms was lower than the ratio in
      healthy subjects. Patients with gallbladder inflammation that underwent
      laparoscopy had an increased percentage of specifically bound IGFBP-3 to SNA
      compared with healthy subjects. Our conclusion is that open surgery decreased the
      level of IGFBP-3 compared with laparoscopy, whereas patients with gallbladder
      inflammation that underwent laparoscopy had an increased content of sialic acid
      in IGFBP-3.

PMID- 17191669
TI  - Loss of consciousness as criterion of +Gz tolerance at Institute of Aviation
      Medicine MMA during +Gz acceleration selective test.
AB  - +Gz induced loss of consciousness (G-LOC) is one of the most serious threats to
      aircrews flying high performance fighter aircraft. From the early beginning of
      use of our Centrifuge, use in selection was primary task. As a functional
      "endpoints" we use criteria: loss of peripheral vision, extreme pulse rate (above
      180 b.p.m.), arrhythmias and loss of consciousness. The key-method in selection
      the candidate who tolerates +Gz stress on the best way is selection by common
      selective centrifuge "Test of linear increasing of acceleration" (TOLIA). We used
      gradual onset rate (GOR--0.1 G/s) and maximum/peak value: +5.5 Gz, +6.0 Gz and
      7.0 Gz. Applied peak value depends on the goal of the test. The lowest peak value
      is for candidates planned for Air Academy, higher peak value is for those pilots
      planned for training to supersonic combat aircrafts and the highest peak value is
      for pilots who are planned to fly High performance combat aircrafts. We examined
      2192 candidates in the last 20 years. Eleven subjects experienced G-LOC episodes.
      All episodes of G-LOC had occurred occasionally and without warning symptoms
      (loss of peripheral vision, gray out, blackout). The percentage of subjects
      having G-LOC episodes was 0.50%. Nine subjects experienced G-LOC during primary
      selection (+5.5 Gz), one G-LOC were observed at secondary selection (+6.0 Gz) and
      one G-LOC was observed during tertiary selection (+7 Gz). G-LOC is the only
      "endpoint" in the centrifuge selection which disqualifies the candidate at once
      and forever for planned flying duties. The other "endpoints" (loss of peripheral
      vision, heart rate above 180 b.p.m., arrhythmias) allow one more testing, not
      less than seven days later.

PMID- 17191670
TI  - ED case managers can improve throughput, reduce denials.

PMID- 17191671
TI  - Value-based purchasing gives CMs chance to shine.

PMID- 17191673
TI  - CMs partner with coders for appropriate documentation.

PMID- 17191672
TI  - Initiative helps to improve patient throughput.

PMID- 17191674
TI  - ED CMs improve throughput as patient advocates.

PMID- 17191675
TI  - Sutter DM, CM programs strike balance for best patient outcomes.

PMID- 17191676
TI  - 'Ideal patient day' gives heads-up on care.

PMID- 17191677
TI  - Identification of antibiotic clarithromycin binding peptide displayed by T7 phage
      particles.
AB  - Peptide libraries displayed by T7 phage, which contain random cDNA fragments
      insets, were screened for their ability to bind to a biotinylated derivative of
      clarithromycin. Phage particles bound to an immobilized derivative of the
      antibiotic were isolated and the inserted cDNA was amplified and sequenced. A
      common selected peptide sequence, composed of 19 amino acids, was obtained and a
      synthetic peptide with this sequence was produced. Surface plasmon resonance
      experiments showed that the synthetic peptide immobilized on a sensor chip bound
      to clarithromycin and the dissociation constant was determined to be 2.1 x 10(-3)
      M. The dissociation constants of other macrolide antibiotics, erythromycin,
      roxithromycin, azithromycin and josamycin were also determined to be 5.4 x 10(-3)
      M, 6.2 x 10(-5) M, 1.1 M and 3.4 x 10(-2) M, respectively. These results
      indicated that T7 phage display method might be useful to determine relatively
      weak interactions between small molecule drugs and the selected peptides which
      could represent a possible binding site conserved in binding proteins.

PMID- 17191678
TI  - Talosins A and B: new isoflavonol glycosides with potent antifungal activity from
      Kitasatospora kifunensis MJM341. I. Taxonomy, fermentation, isolation, and
      biological activities.
AB  - In our screening program for new antifungal agents from microbial secondary
      metabolites, we isolated two new isoflavonol glycosides, genistein 7-alpha-L-6
      deoxy-talopyranoside (talosin A) and genistein 4',7-di-alpha-L-6-deoxy
      talopyranoside (talosin B), from the culture broth of Kitasatospora kifunensis
      MJM341. The talosins exhibited strong antifungal activity against Candida
      albicans, Aspergillus niger and Cryptococcus neoformans with minimal inhibitory
      concentrations (MIC) in the range of 3- 15 microg/ml while genistein and
      genistein-7-glucopyranoside did not show antifungal activity at 100 microg/ml.
      These talosins are the first isoflavonol glycosides with a 6-deoxy-talose sugar
      component and they may be useful as antifungal agents with low toxicity because
      of no visible cytotoxicity against the human hepatic HepG2 cell.

PMID- 17191679
TI  - Talosins A and B: new isoflavonol glycosides with potent antifungal activity from
      Kitasatospora kifunensis MJM341. II. Physicochemical properties and structure
      determination.
AB  - In our screening program for new antifungal agents from microbial secondary
      metabolites, two new isoflavonol glycosides, with potent antifungal activity,
      talosins A and B, were isolated from the culture broth of Kitasatospora
      kifunensis MJM341. Talosins A and B were determined to be genistein 7-alpha-L-6
      deoxy-talopyranoside and genistein 4',7-di-alpha-L-6-deoxy-talopyranoside,
      respectively, by spectroscopic studies. They are the first flavonoid glycosides
      incorporating 6-deoxy-talose as a sugar component.

PMID- 17191680
TI  - Yaequinolones, new insecticidal antibiotics produced by Penicillium sp. FKI-2140.
      I. Taxonomy, fermentation, isolation and biological activity.
AB  - New nine insecticidal antibiotics designated yaequinolones were isolated from the
      culture broth of the fungal strain Penicillium sp. FKI-2140 by solvent
      extraction, centrifugal partition chromatography and HPLC. Yaequinolones showed
      growth inhibitory activity against brine shrimp (Artemia salina). Among them,
      yaequinolone F has the most potent activity with MIC value of 0.19 microg/ml.

PMID- 17191681
TI  - Yaequinolones, new insecticidal antibiotics produced by Penicillium sp. FKI-2140.
      II. Structural elucidation.
AB  - The structure and relative stereochemistry of yaequinolones, fungal insecticidal
      antibiotics, were elucidated by spectroscopic studies, including NMR spectral
      analyses. Yaequinolones possess a p-methoxyphenylquinolinone skeleton modified
      with different isoprenyl-derived side chains.

PMID- 17191682
TI  - Oxachelin, a novel iron chelator and antifungal agent from Streptomyces sp.
      GW9/1258.
AB  - During a screening campaign for new antimicrobial and antifungal secondary
      metabolites from several thousand actinomycetes, a novel compound, isolated by
      activity guided fractionation, was oxachelin (1) from the new Streptomyces sp.
      GW9/1258. Oxachelin shows strong antibiotic activities against several fungi and
      Gram(+) bacteria. Additionally, oxachelin is a strong complexing ligand for Fe3+
      (siderophore), possibly making it useful e.g. for iron excess diseases.

PMID- 17191683
TI  - Cruentaren, a new antifungal salicylate-type macrolide from Byssovorax cruenta
      (myxobacteria) with inhibitory effect on mitochondrial ATPase activity.
      Fermentation and biological properties.
AB  - The novel macrolide cruentaren A was produced at levels up to 3.2 mg/liter by
      cultures of the myxobacterium Byssovorax cruenta. The new compound strongly
      inhibited the growth of yeasts and filamentous fungi and showed high cytotoxicity
      against L929 mouse fibroblast cells. A minor co-metabolite of cruentaren A, named
      cruentaren B, and identified as a six-membered lactone isomer of cruentaren A,
      showed only marginal cytotoxicity and no antifungal activity. Cruentaren A
      inhibited F0F1 mitochondrial ATP-hydrolysis in submitochondrial particles of
      yeasts and beef heart.

PMID- 17191684
TI  - Marasmane sesquiterpenes isolated from Russula foetens.
AB  - One lactone marasmane sesquiterpene named 8a,13-dihydroxy-marasm-5-oic acid gamma
      lactone (1) and one unsaturated marasmane sesquiterpene named 13-hydroxy-marasm
      7(8)-en-5-methoxy gamma-acetal (2) together with a known compound: 7alpha,
      8alpha, 13-trihydroxy-marasm-5-oic acid gamma-lactone (3) were isolated from the
      fruiting bodies of Russula foetens. Their structures were established on the
      basis of spectral methods (MS, IR, ID and 2D NMR experiments).

PMID- 17191685
TI  - A firm foundation.

PMID- 17191686
TI  - The second century--advocating for our colleagues.

PMID- 17191687
TI  - Effective components of treatment for the chemically dependent physician.
AB  - Physicians with substance use disorders have been documented throughout history.
      In 1973 the American Medical Association (AMA) acknowledged that physicians
      suffered from addiction with a landmark policy paper and subsequent Physician
      Health Conference. Since that time extensive information has been collected
      regarding the evaluation and treatment of physicians who have the disease of
      addiction. It is estimated that addiction affects ten percent of the current
      physician population. Effective treatment for these individuals centers around
      the fact that addiction is a chronic disease. Treatment initially requires
      intensive care for stabilization, education, and denial reduction. Ongoing
      treatment is then needed to help solidify gains made in primary treatment, modify
      self-care behaviors and attitudes, and to hopefully prevent relapse.

PMID- 17191688
TI  - Is there a correlation between TV alcohol advertisement exposure and adolescent
      alcohol use?

PMID- 17191689
TI  - Part III. Penicillins.

PMID- 17191690
TI  - [Dissection of the heart: a useful guide to understanding the three-dimensional
      gross anatomy].
AB  - In order to understand the three-dimensional gross anatomy of the heart, it is
      important to observe the inner structures of the chambers and the spatial
      relation between the valves and the ventricles. In our dissecting laboratory, we
      designed a guide to dissection of the heart according to the following
      procedures. First, we observe the surface anatomy of the heart in the pericardial
      cavity, remove the heart and then identify the coronary vessels, open the four
      chambers and observe the intra-cardiac structures. Next, we remove the atria from
      the ventricles and examine the relation between the valves and the chambers. Our
      guide is useful for learning the three-dimensional gross anatomy which is
      fundamental to understanding the normal function and disease of the heart.

PMID- 17191691
TI  - [Tutorial session using cross sections of upper and lower limbs in human gross
      anatomy course].
AB  - We performed tutorial education in gross anatomy using thick serial cross
      sections (3-4 cm) of one of the upper or lower limbs of a cadaver donated for use
      in the macroscopic dissection course. Group learning (four people) proceeded with
      the extraction of the point in question from an arbitrary section. Consequently
      students obtained a deeper understanding of the cross sectional structure of an
      upper or lower limb and further deepened their understanding of the three
      dimensional structure of limbs. Each group collected clinical images of the part
      corresponding to the selected section to present, thus bringing together the
      relationship between the anatomical knowledge studied from the specimen and the
      related disease. A questionnaire survey after the practicum suggested that the
      practice of using serial cross sections and the presentation of relevant images
      using Microsoft PowerPoint were effective means of the study. Useful points on
      the student's understanding were collected with respect to the following three
      opinions: Fresh aspects, Grasp of the position, and Three-dimensional views.
      Moreover, the dissection program in gross anatomy combined with thick cross
      sections was thought to be helpful in that not only was observing the cross
      structure but also to dissect it if necessary, with the students obtaining a
      deeper understanding of the structure as a result. In our anatomy practice
      thereafter, the practicum was done with awareness of the issues faced by the
      students in mind. It was concluded that the practicum that uses the cross
      sections is an effective means in gross anatomy education.

PMID- 17191692
TI  - [Structure-function and mode of action of major toxins from Clostridium
      perfringens].

PMID- 17191693
TI  - [Heliobacter pylori-related thrombocytopenic purpura].

PMID- 17191694
TI  - [Chemical structure and immunobiological activity of Bacteroides species LPS
      based on study of Porphyromonas gingivalis LPS].

PMID- 17191695
TI  - [Immune recognition of mycobacteria-derived lipid components].

PMID- 17191697
TI  - [Potential of active specific immunotherapy using allogeneic vaccines in
      treatment of malignancies].

PMID- 17191696
TI  - [Prophylaxis of breast cancer in patients with reproductive system
      hyperproliferative pathologies].

PMID- 17191698
TI  - [Use of cyto-differentiating agents in oncology].

PMID- 17191699
TI  - [Malignant melanoma: present-day trends (morbidity, mortality, diagnosis and
      morphological verification)].

PMID- 17191700
TI  - [Use of endoscopic surgery and combined radiotherapy for inoperable cancer of the
      esophagus].
AB  - A comparative evaluation of the efficacy of combined radiotherapy (112 - group 1)
      carried out in conjunction with a battery of procedures of endoscopic surgery
      plus combined radiotherapy (76 - group 2) for inoperable cancer of the esophagus
      was conducted in 118 patients. Maximum local regression was reported in group 2
      (77.6%) as compared with only 33.9% in group 1. Relatively longer relapse-free
      period (133 days) and lower residual growth incidence (44.6%) were in group 2,
      too, as compared with 107 days and 63.5% in group 1. Mean survival duration was
      nearly identical in both groups - ca.15 months. Similarly, survival rates in
      groups 2 and 1 were: 69.2 and 58.8% (year 1), 22.2 and 22.3% (year 2), and 11.3
      and 12.9% (year 3), respectively. It was concluded that combinations of
      endoscopic surgery and combined radiotherapy for inoperable cancer of the
      esophagus improved immediate results and reduced the rates of residual tumor
      incidence. However, no significant differences in mean duration or rates of
      survival were observed.

PMID- 17191701
TI  - [Signet ring cancer of the stomach: clinico-morphological features, postsurgical
      results and prognosis].
AB  - Clinico-morphological features of signet ring cancer of the stomach were
      evaluated in 372 out of 2,308 gastric cancer patients undergoing gastroectomy or
      stomach resection. Signet ring tumor pathology occurs mostly in young females and
      younger patients generally. It features high incidence of early cancers, low
      frequency of metastatic spreading to lymph nodes (T1-T2), high frequency of
      immediate involvement of perigastric fatty tissues, peritoneum and ovaries and
      infrequent spreading to the liver. Post-surgical survival rates among patients
      with T1-T2 were relatively high, yet declining in cases of extension through the
      serous membrane of the stomach. D2-lymphdissection failure to improve the end
      results of surgical treatment of signet ring cancer might be accounted for by the
      predominance of peritoneal metastases of this morphological pattern.
      Histochemical assay of mucines might be contribute additional data on prognosis.

PMID- 17191702
TI  - [Multivariate analysis of significance of prognostic factors of immunological
      response and stomach tumor growth].
AB  - Significance of prognostic factors of immunological response, tumor growth and
      age was investigated in 708 patients with stomach cancer. Such factors as T-cell
      immunological response, functional status of lymph nodes and localization on
      either the greater or lesser curvature of the stomach were identified as the most
      significant while T-cell immunological response, tumor size and number of
      involved lymph nodes appeared less significant but more harmful as far as
      survival was concerned. No significant correlation between pattern of growth,
      depth of invasion, age and local immunological response, on the one hand, and
      survival, on the other, was established.

PMID- 17191703
TI  - [Immunological indices in gastric cancer].
AB  - Immunological indices were assayed in 167 patients with gastric cancer. Tumor
      growth involved reduction in levels of neutrophil peroxide (p<0.05), CD3+ and
      CD19+-cells (p<0.05) as well as intensification of apoptosis of lymphocytes
      (p<0.05). As monocytic and granulocytic phagocytosis (p<0.001) and HLA-DR
      expression in monocytes (p<0.001) diminished, and mitogen-induced proliferative
      activity of mononuclear cells suppressed (p<0.05), total and relative levels of
      CD8+-cells (p<0.05) and spontaneous proliferative activity of mononuclear cells
      (p<0.05) in peripheral blood increased. Such changes should not be reganded as
      expression of immunosuppression alone. Mechanisms of immunological failure
      inherent in tumor growth need to be investigated further.

PMID- 17191704
TI  - [Synchronous polyneoplasia of the thyroid gland: problems of diagnosis and
      therapy].
AB  - Thyroid carcinoma concurrent with synchronous polyneoplasia is quite rare and not
      fully understood. There are 15 cases of such carcinoma on the records of the
      Center (2000-2005) (papillary and medullar - 9, papillary and follicullar -3,
      papillary and anaplastic - 1, papillary - 1 and unidentified well differentiated
      carcinoma - 1). Still another patient had a combination of Hodgkin's disease
      (nodular sclerosis, cellular stage) and papillary microcarcinoma dicceminated to
      lymph nodes. Problems of diagnosis and therapy are discussed.

PMID- 17191705
TI  - [Radiation assisted diagnosis and complex treatment of penile carcinoma].
AB  - Recurrence-free survival rate after conservative treatment of penile carcinoma
      was as high as 81%. The best results were obtained with use of combined
      radiotherapy (monotherapy and telegamma therapy concurrent with penile resection
      or circumcision) (91.6 and 75%, respectively). Organ-saving treatment was most
      effective in T1-T2 penile carcinoma while MRI yielded the most reliable
      diagnostic evidence on depth of primary tumor invasion and regional lymph node
      involvement.

PMID- 17191706
TI  - [Outcomes prediction for children with Hodgkin's disease].
AB  - A prognostic score was developed in the course of treatment of 551 pediatric
      patients with Hodgkin's disease stage I-IV (1967-2001). It took care of such
      significant factors of uni-and multivariate analysis as age (11 years or more),
      peripheral lymph node involvement (5cm or more), systemic symptoms (B),
      histological pattern for lymphocytic depletion, IVB stage and/or extranodal
      disease (E) and biological rate of tumor process ("b"). As a result, three groups
      at risk were identified: favorable prognosis (65.8%: overall survival - 92%,
      relapse-free - 67%), medium risk (17.8%: overall survival - 67%, relapse-free
      48%) and high risk (16.4%: overall survival - 38%, relapse-free 25%). Our data
      may be used to estimate the scope of risk-adapted therapy for Hodgkin's disease.

PMID- 17191708
TI  - [Effect of exogenous dna injection on leukopoietic repair and antitumor action of
      cyclophosphamide].
AB  - The cytostatic drug cyclophosphamide (CPA) in high dosage suppressed hemopoiesis
      by causing multiple double-strand breaks to occur in hemopoietic cell DNA and
      leading to mutation, chromosomal abberations and finally cell death. We tested
      fragmented DNA drugs for an ability of CPA to protect murine leukopoiesis on an
      assumption that once exogenous fragmented DNA had infiltrated into a cell, it
      might integrate with chromosomal DNA through homologous recombinations thus
      repairing damaged segments. DNA drugs did promote repair of leukocyte count in
      murine peripheral blood with leukopoiesis being suppressed by CPA administration.
      The levels of DNA derived from murine organs and human placenta were higher than
      those from salmon roe. Tumor growth was significantly inhibited following
      injection of placental DNA into mice bearing intramuscularly transplanted
      lymphosarcoma. Antitumor effect of combined CPA and DNA treatment was much higher
      than after CPA alone.

PMID- 17191707
TI  - [Smoking affects metal-ecotoxicant accumulation and genotoxic reactions in
      leukocytes].
AB  - The investigation was concerned with the influence of smoking on manganese (Mn),
      lead (Pb) and cadmium (Cd) content in the blood of metropolitan groups of varying
      age as well as on genotoxic reactions in leukocytes after test irradiation ex
      vivo. The study involved 325 inhabitants of St.Petersburg, aged 10-90 years.
      Venous blood was assayed for metal ecotoxicant content using standard AAS-flame
      method and DNA leukocyte decay following test irradiation (2Gy) ex vivo. Aging
      was shown to involve a sequence of consistently rising metal levels: Cd - Mn Pb.
      Relative accumulation of Pb was greater in males while that of Mn - in females.
      The rates of Cd, Mn, Pb accumulation in smokers were higher than in non-smokers.
      Smoking promoted genotoxic response to testing exposure which induced Cd-related
      disturbances of DHA repair system in males. Among smoking females, risk of
      adverse effects rose as a result of concurrent action of the genotoxic factor. It
      was also evident among female non-smokers when radiation was used in conjunction
      with enhanced concentrations of Mn and Cd. Hence, correlations between smoking
      and Cd, Mn, Pb accumulation, on the one hand, and Cd-related accumulation and
      enhanced genotoxic response in leukocytes, on the other, were established. It is
      likely that carcinogenic risk of tobacco smoking should be accounted for by both
      mere presence of a carcinogenic agent and its potential to promote Cd level thus
      inhibiting withdrawal of carcinogenic DNA adducts from the cellular genome.

PMID- 17191709
TI  - [Role of Mg2+-dependent alkaline endodnaase of blood serum in tumorigenesis in
      A/smail mice].
AB  - An enzymoassay of levels of Mg2+-dependent alkaline endoDNAase of protein
      spectrum of blood serum of noninbred albino mice by SDS-electrophoresis in 10%
      PAAG established a fairly high heterogeneity of the enzyme. The variety of
      alkaline endoDNAases must be due to the limited proteolysis of their high
      molecular precursor by specific proteases as described in the literature. No
      alkaline endoDNAase activity was identified by analysis of 10-150 kDa protein
      spectrum in A/smail line mice without ascites hepatoma. It was detected (pH 8.3)
      in the 25-45 kDa range on day 10 after tumor transplantation. Considering the
      gravity of disease (pre-lethal stage), on day 10, it was suggested that the level
      be accounted for by decay of diseased cells. The lack or extremely low level of
      endoDNAase activity in original blood serum expressed a mechanism of enhancing
      sensitivity to tumor cell effects. In mice bearing ascites hepatoma, the enzyme
      levels (pH 8.3) were much higher on day 10. DNAase activity (pH 7.5) was not
      induced in response to the heterogenous DNA. Our data point to possible defects
      in the induction of Mg2+-dependent alkaline endoDNAases (pH 8.3) and DNAses (pH
      7.5) as well as their role in raising sensitivity to transplantable ascites
      hepatoma.

PMID- 17191710
TI  - [The influence of soybean proteins on melanoma B-16 growth versus free-radical
      mechanisms in tumor-bearing animals].
AB  - The study deals with antitumor action of soybean proteins as natural bio
      mediators for alleviating side-effects of chemotherapy. The influence of soybean
      proteins on antibody formation and free-radical mechanisms in blood serum was
      assessed in melanoma B-16-bearing mice. Use of soybean proteins was followed by a
      65% rise in inhibition of tumor growth and an 1.4-fold increase in survival time.
      In particular, an enhanced level of antibody formation cells in the spleen and
      normalization of oxidative processes in blood serum were reported.

PMID- 17191711
TI  - [Use of video-assisted thoracoscopy in diagnosis and therapy of single circular
      formations in the lung].
AB  - An evaluation is presented of the data on use of video-assisted thoracoscopy in
      the diagnosis and therapy of 45 patients with single circular formations in the
      lung. Indications and contraindications for the management of benign and
      malignant single tumors of the lung are discussed alongside a review of the
      Russian and foreign literature.

PMID- 17191712
TI  - [Chronic atrophic gastritis: morphological features and pepsin formation
      function].
AB  - The paper discusses a modern approach to chronic atrophic gastritis as a
      precancerous gastric condition. It deals with the role of Helicobacter pylori
      infection, development of disease, morphological changes taking place in gastric
      mucosa associated with chronic atrophic gastritis, and their importance for
      gastrocarcinogenesis. Recommendations are given on the strategies of management
      of precancerous gastric changes in mucosa as well as early prophylaxis of stomach
      cancer development from chronic atrophic gastritis associated with Helicobacter
      pylori infection.

PMID- 17191713
TI  - [Cardiovascular disorders in Hodgkin's lymphoma occurring at different stages
      after specialized treatment].

PMID- 17191714
TI  - [Comparative evaluation of clinical efficacy of combined treatment (surgery and
      radiotherapy) for extremity soft-tissue sarcomas in patients who underwent organ
      saving operations].
AB  - Clinical efficacy of combined treatment of 383 patients who had undergone
      conservative surgery for extremity soft-tissue sarcomas (combined treatment -188;
      surgery alone - 195, control) was assessed. The comparison, which included
      prognostic factors, established the advantages of combined treatment in all
      groups. Thus, overall 5-year survival time was in 64.3+/-2.8%, with combined
      treatment - 72.2+/-3.3% and surgery - 56.8+/-3.5%, t>2. Application of
      radiotherapy as a component of combined modality treatment made feasible a wider
      range of organ-saving operations. Differences in the frequency of postoperative
      complications after surgery and combined treatment were insignificant and of
      similar patterns.

PMID- 17191715
TI  - [On certain low-cost approaches in improving efficacy of cancer patients
      treatment].

PMID- 17191716
TI  - [Microscopic myocardial changes and their significance for forensic medical
      diagnosis].
AB  - Morphological myocardial changes essential for diagnosis in forensic medical
      medicine are listed as well as alterations in the vessels of the myocardium,
      cardiac muscular fibers and cardiomyocytes important for diagnosis of death of
      ischemic heart disease, acute alcohol poisoning, alcohol cardiomyopathy, closed
      cardiac lesions. Changes induced by reflex impacts on the heart and postmortem
      alterations are also shown.

PMID- 17191717
TI  - [Characteristics of traumatic death of people in high mountains].
AB  - Lethal accidents with tourists who died of trauma in high mountains of Kabardino
      Balkaria were retrospectively studied for the period from 1978 to 2003. The
      victims were 163 males and 17 females aged 14-72 years. Among causes of death
      most prevalent was a step-by-step blunt mechanical trauma as a result of falling
      from a great height. In such conditions the body obtains great kinetic energy
      causing a severe, often lethal, craniocerebral injury with destruction of the
      brain, blunt injury of the chest, thoracic and other organs.

PMID- 17191718
TI  - [The variant of forensic-medical examination of the hypothalamic-hypophyseal
      system in cases of death due to a mechanical trauma].
AB  - The authors propose the method of total isolation of the hypothalamic-hypophyseal
      system for more effective study of causes of death in craniocerebral injury and
      pathology in expert practice. The method can be also applied for making an
      anatomic preparation of the brain and hypophysis in teaching anatomy.

PMID- 17191720
TI  - [The role of histological examination in timing of the splenic injury].
AB  - Basing on her findings at forensic-histological investigations of splenic
      injuries, the author describes histological inflammatory-reparative alterations
      in splenic tissue in the rupture regions regarding time parameters. The
      investigations allow prescription of splenic damage.

PMID- 17191719
TI  - [Comparative characteristics of hydration distribution in various structures of
      the brain in the deceased of a severe cerebrocranial trauma].
AB  - Hydration in the brain structures was analysed in 34 victims who had died of a
      severe craniocerebral trauma with pathological processes (hematoma, foci of brain
      crushing) of different location. Some of the patients had undergone open
      operations on the brain. Mosaic distribution of water was revealed in various
      structures of the brain where normohydration and dehydration occurred more often
      than hyperhydration.

PMID- 17191721
TI  - [Comparative characteristics of angulometric parameters of teeth and dentitions
      in terms of personal identification].
AB  - Angulometric teleroentgenographic characteristics of teeth were compared for 158
      subjects. A computer technology of calculation and assessment of 47 angular
      (quantitative) parameters characterizing spatial position of the teeth and jaws
      is proposed. This complex of parameters can be used as an additional test in
      personal identification.

PMID- 17191722
TI  - [Assessment of accumulation of the shot products on the targets in shooting from
      a short-barreled gun with a muffler for estimation of shooting distance].
AB  - A practical expert task--to estimate shot distance and order of shots made in two
      victims from a gun with muffler--is described as illustration of opportunities of
      the complex investigation with experimental shots and emission spectral analysis
      of the targets. Distribution of the shot soot on the targets in shooting from the
      distance up to 1 m is analyzed.

PMID- 17191723
TI  - [Forensic-biochemical indices of serum amilase and cholinesterase activity in
      lethal poisoning with heroin].
AB  - The examination of the activity of serum amilase and cholinesterase in the blood
      from subjects who had died of heroin poisoning showed significant elevation of
      such activity. These findings allow experts to use the activity of the above
      enzymes as effective markers in detection of narcotic drugs in cadaveric blood,
      opiate narcotics, in particular.

PMID- 17191724
TI  - [Strategy of multiplex analysis of STR-loci polymorphism of Y-chromosome on the
      basis of "minimal haplotype"].
AB  - A molecular-genetic analysis of Y chromosome is a convenient tool of paternal
      affinity determination. This method is now widely introduced in expert practice.
      Previous experience in typing of Y chromosome is outlined. Strategy of
      development and experience in operating a multiplex system for a simultaneous
      analysis of seven STR loci of Y chromosome is discussed.

PMID- 17191725
TI  - [Identification of tsunami victims in Thailand: international experience in
      organization and conduction of forensic-medical expert investigations in
      emergency situations with many victims].
AB  - Russians were among the victims of tsunami in Thailand. The authors participated
      in the activity of Thai Tsunami Victim Identification Center as experts for
      identification of tsunami victims. The article outlines management and course of
      identification, some results. The unique experience with international
      cooperation in conduction of forensic-medical expert investigations in emergency
      situations with many victims is discussed.

PMID- 17191726
TI  - [Estimation of ethanol concentrations in biological media. Comparison of
      alkylnitrite and direct vapor-phase methods].
AB  - Ethanol assays in the blood, saliva and urine were made according to two methods:
      alkylnitrite gas-liquid chromatography and direct vapor-phase method without
      thermostating. N-propanol was used as an internal standard. For saliva and urine
      the methods produced similar results. For blood, the direct vapor-phase method
      detected significantly lower level of ethanol compared to alkylnitrite one (p =
      0.001). 24-h storage of the samples in refrigerator does not deviate the results.
      Recommendations are provided for most effective usage of each method.

PMID- 17191728
TI  - [Forensic-histological diagnosis of live-born fetuses].

PMID- 17191727
TI  - [Forensic-medical assessment of facial injuries inflicted by rubber bullets].

PMID- 17191729
TI  - [The lost manuscript].

PMID- 17191730
TI  - Bilateral shoulder fracture dislocations and radiculopathies secondary to
      electrical injury (a case report).
AB  - INTRODUCTION: In this report a case of bilateral shoulder fracture dislocations
      and C5 radiculopathy developed after an electrical injury is presented. CASE: A
      29 year-old male patient referred to our hospital with complaints of inability to
      raise his hands overhead starting 3 months ago after an electrical injury. The
      first physical examination revealed loss of strength (3/5) in deltoid muscles
      bilaterally, bilateral shoulder fracture dislocations and C5 radiculopathies. An
      open reduction and internal fixation (using K wire, cortical screw) procedure was
      applied for the right side in the Department of Orthopedics. Postoperatively
      active (A) and passive (P) ranges of motion (ROMs) were restricted extremely in
      the right and left shoulder respectively. Since applications of 15 sessions of
      electrical stimulation for deltoid muscle and physical treatment for both
      shoulders failed to achieve satisfactory ROMs, K wire extraction was instituted
      with resultant increase in the right shoulder A/P ROMs after 10 sessions of
      physical therapy postoperatively. At the last examination which was 18 months
      after the injury, ROMs of the right shoulder were increased, but not normal.
      CONCLUSION: It must be remembered that in electrical injury, fractures and
      dislocations might occur in affected sites without any evidence of trauma with
      associated neurologic complications, and that these cases must be promptly
      detected and managed without any delay.

PMID- 17191731
TI  - Influence of different stimuli on electromyographic variables of the biceps
      brachii.
AB  - The objective of this study was to assess the influence of different stimuli on
      the muscular response of 30 young sedentary male and female subjects. A
      conditioning module with A/D 16/32 signals of 12 bits (LYNX), with band-pass
      filter of 10-500 Hz and sampling frequency of 1000 Hz was used. A bipolar active
      surface electrode (LYNX), a load cell (MM-100 KRATOS) and a pressure cuff were
      also used. The volunteers were submitted to four conditions: Without stimulus
      (WS), auditive stimulus (AS), visual stimulus (VS), and auditive + visual stimuli
      (AVS). Matlab 6.5.1 software was used to process the signals for analyzing RMS
      and median frequency (MF), as well as muscular force (F) and cuff pressure (P).
      Statistical analysis consisted of the Wilcoxon and Mann-Whitney test with a
      critical level of 5%. As to RMS, females presented a significant increase in all
      types of stimuli compared to WS. As to MF there was no significant difference
      between the different groups for either sex. P in both sexes presented a
      significant increase when submitted to VS and AVS. F was higher for AVS in males
      and for any of the stimuli in females when compared to WS. In all the variables
      analyzed, males presented significantly higher values than females for all types
      of stimuli.

PMID- 17191732
TI  - Comparison of the utility of sympathetic skin response and current perception
      threshold examinations with conventional examinations for the early
      electrophysiological diagnosis of diabetic polyneuropathy.
AB  - We compared the utility of sympathetic skin response (SSR) and current perception
      threshold (CPT) with that of conventional electrophysiological examinations like
      sural sensory conduction velocity, sensory nerve action potential (SNAP),
      peroneal motor conduction velocity, compound muscle action potentials, and F-wave
      latency. Twenty-two type II diabetic patients (mean age, 69.6 years) without
      sensory symptoms and with a mean glycosylated hemoglobin (HbA1c) level of 7.1%,
      along with 26 age-matched control patients, were examined. Among the conventional
      examinations, only the sural SNAP was considerably (although not significantly)
      depressed in the diabetic group. On the other hand, the mean SSR amplitude in the
      diabetic group was approximately half of the value in the control group. All the
      CPT values were also considerably lower in the diabetic group than in the control
      group, although only the values for hand stimulation at 2000 and 250 Hz were
      significant. No correlations were observed between the SSR amplitudes and the CPT
      values at any of the test frequencies. However, a positive correlation between
      the mean HbA1c level and the CPT value was seen at all frequencies. We concluded
      that SSR amplitude measurements are superior to conventional examinations and CPT
      studies with regard to the early electrophysiological diagnosis of diabetic
      polyneuropathy. Furthermore, CPT values may be useful as an electrophysiological
      surrogate indicator of recent glycemic control.

PMID- 17191733
TI  - Transcranial stimulation parameters to elicit motor evoked potentials.
AB  - PURPOSE: We studied effectiveness of single, paired, and repetitive transcranial
      electrical stimulation to activate motor cortex in patients during spine surgery.
      METHODS: In ten consented patients, the latency and amplitude of the muscle
      action potential from abductor pollicis brevis muscle after cortical stimulation
      was measured. RESULTS: The number of responses evoked by double (pair) pulse
      stimulation was significantly higher than that evoked by single pulse (p =
      0.0191). A similar finding was obtained between the repetitive and single pulse
      stimulation (p = 0.0001). The repetitive stimulation was more effective than the
      double pulse stimulation (p = 0.0253). An increase of interstimulus interval
      (ISI), between pulses, from 1-3 msec did not significantly alter latency (p >
      0.05) or amplitude (p > 0.05) with the double pulse or repetitive stimulations.
      The latency or amplitude did not significantly change with varying number of
      electrical pulses from 3-9. CONCLUSIONS: This study shows that the intraoperative
      repetitive transcranial stimulation is the most effective method to activate
      descending motor tracts under anesthesia.

PMID- 17191734
TI  - Comparison of electrically and mechanically induced soleus H-reflex depression.
AB  - OBJECTIVES: The aim of the present investigation was to compare the responses of
      mechanically-evoked and electrically-evoked conditioning among three different
      stimulus intensities and provide possible insight in determining whether these
      two types of inhibitory conditioning demonstrate the same response across the
      motor pool. METHODS: The soleus H-reflex was tested under three different
      stimulus intensities (25% Hmax, 50% Hmax, and Hmax), and peak to peak amplitudes
      were recorded after either mechanical or electrical conditioning. For electrical
      conditioning, the ankle was held at 90 degrees, whereas mechanical conditioning
      utilized a 10 degree passive dorsiflexion at 15 degrees/sec back to the 90 degree
      position. All H-reflex measurements were recorded with the ankle at 90 degrees.
      RESULTS: A 3 x 2 (stimulus intensity x treatment condition) repeated measures
      ANOVA indicated significant main effects for stimulus intensity (FGG = 16.23; p =
      .003) and condition (FGG = 28.48; p < .001), as well as an interaction (F(2,18) =
      6.59; p = .008). Simple main effects identified significantly more H-reflex
      depression for mechanical conditioning (94%, 91%, and 44%) compared to electrical
      conditioning (65%, 55%, and 19%) at 25% Hmax, 50% Hmax, and Hmax, respectively.
      CONCLUSIONS: There appears to be more mechanically than electrically stimulated H
      reflex depression when testing at 25% Hmax, 50% Hmax, and Hmax. These results
      demonstrate the influence of Ia discharge properties on H-reflex depression and
      may suggest differences in the affinity of Ia terminals to intrinsic presynaptic
      inhibition at different stimulus intensities.

PMID- 17191735
TI  - Symmetry diagnosis and treatment in coordination dynamics therapy.
AB  - Forward-backward movement symmetry of the human CNS was investigated through
      pattern change during exercising on a special coordination dynamics therapy and
      recording device in the forward and backward direction. A mirror-image symmetry
      shift was found in a patient with cerebellar injury for the attractor patterns
      (movement patterns with the highest temporal stability) for exercising on the
      special coordination dynamics therapy device in forward and backward direction,
      with respect to pace and trot gait coordinations. Symmetry diagnosis and symmetry
      treatment are of importance in CNS repair because of the learning transfer to the
      movement symmetry counterpart: training of backward walking improves forward
      walking The theoretical and practical basis of Schalow Coordination Dynamics
      Therapy is given in the Method section including symmetry considerations with
      respect to CNS self-organization.

PMID- 17191736
TI  - Improvement after cerebellar injury achieved by coordination dynamics therapy.
AB  - Coordination dynamics therapy of changing intensity was administered at home for
      nearly 8 years (at the beginning at low intensity) to a patient who had suffered
      a severe injury of the cerebellum (and of the cerebrum). Motor functions improved
      markedly during the first year of rather intensive therapy (by 42%), but there
      was but little improvement in the 5 following years (by 27%). An intensive 3-week
      coordination dynamics therapy was administered after 4 years of quantified
      therapy at an up-to-date therapy place under optimal conditions. The motor
      functions improved strongly (by 29% in 13 days). Therapy under professional
      conditions was shown to be much more efficient (by the factor of 150 as
      quantified by low-load coordination dynamics values) than that at home. A
      comparable patient with a brain (cerebral) injury improved slightly more under
      optimal conditions (by the factor of 390). In the patient with the injury of the
      cerebellum, the largest improvement concerned speech and higher mental functions.
      The strong improvement during the 3-weeks of optimal therapy may have partly been
      due to the enhanced training of CNS symmetries. It thus seems that not only phase
      and frequency coordination between neuron firings has to be improved by the
      therapy, but also symmetries in CNS organization.

PMID- 17191737
TI  - Electromyographic analysis of the pectoralis major and deltoideus anterior in the
      inclined "flying" exercise with loads.
AB  - Due to a shortage of textbooks with specific data on muscular activity concerning
      physical conditioning and sports, we analysed electromyographically the muscles
      pectoralis major and deltoideus anterior, bilaterally, in inclined "flying"
      exercises, during the concentric and eccentric phases, with external loads of 25,
      50, 75 and 100% of the maximum load. The electromyographic analysis was performed
      in eleven male volunteers with MEDI-TRACE-200 surface electrodes connected to a
      six-channel biologic signal acquisition module coupled to a PC/AT computer. The
      electromyographic signals were processed and the obtained effective values were
      normalized through maximum voluntary isometric contraction. Statistically, the
      results showed that all the muscles studied presented significant differences
      between the concentric and the eccentric phases, with higher electromyographic
      activity during the concentric phase. By analysing the different loads for each
      muscle in both phases, significant electromyographic activity was observed for
      all muscles. When the effect of each load on each muscle during the concentric
      phase was analysed, it was noticed that the muscles on the left were more active
      than those on the right side, while in the eccentric phase the muscles had
      different behavior.

PMID- 17191738
TI  - [Image of the month. Uterine varices secondary to a congenital absence of the
      inferior vena cava].

PMID- 17191739
TI  - [How I treat...a patient presenting with mycosis fungoides].
AB  - Primary lymphomas of the skin exhibit singular clinical, histological and
      prognostic features that are not shared by lymphomas originating from the
      lymphoid tissues. This review is an update of the current concepts about the
      diagnosis and treatment of mycosis fungoides, the most frequent entity among the
      primary cutaneous lymphomas.

PMID- 17191740
TI  - [Uterine perforation by an intrauterine device].
AB  - The intrauterine device (IUD) is a widely used, effective and reversible means of
      birth control. Its insertion can be associated with perforation of the utuerus.
      This is a rare complication, but with possible serious clinical consequences.
      There is an increased risk of uterine perforation if the IUD is inserted during 6
      months of post-partum or after uterine evacuation. A follow up by sonography is
      essential. The surgical removal of the ectopic IUD is imperious.

PMID- 17191741
TI  - [Clinical case of the month: clostridium difficile colitis].
AB  - A 55-year-old patient with mant e cels underwent a cytotoxic chemotherapy
      (D.H.A.P. + Rituximab). During the medullar aplasia related to the third cycle,
      diarrhoea due to Clostridium difficile arised and relapsed 15 days later despite
      normal blood counts. This colitis was very severe with pluribacterial
      peritonitis, but resolved with intensive medical treatment. The incidence, the
      patient's risk factors, the iatrogenic and nosocomial characters of cl. difficile
      colitis are discussed.

PMID- 17191742
TI  - [Clinical case of the month. Compression of the right main bronchus by a
      mesothelioma].
AB  - We report the case of a patient treated by chemotherapy for a diagnosis of
      mesothelioma. A quickly progressive dyspnea developed which was due to
      compression of the right main bronchus by mediastinal extension of the tumor.
      This obstruction was treated by interventionnal bronchoscopy and stenting.

PMID- 17191743
TI  - [New approaches to prenatal diagnosis of rhesus incompatibility].
AB  - Despite generalisation of anti-D immunoprophylaxis, RhD allo-immunisation still
      remains the major cause of severe haemolytic disease of the fetus and of the
      newborn (HDFN). The routine follow up of pregnant women comprises: the ABO/D,
      Rh/Kell red cells typing and the search for irregular antibodies. In case of anti
      D immunisation, the paternal Rh phenotype, when known, provides useful
      information regarding the probability for the fetus to have inherited the D
      antigen and thereby to be exposed to the risk of HDFN. The antibody titre, which
      is predictive of possible in vivo haemolysis, must be interpreted in the light of
      the previous obstetric history, and can lead to the decision of invasive
      amniocentesis. Then the measurement of the optical density (deltaOD450 nm) and
      the fetal RhD typing can be realised on amniotic fluid. New molecular techniques
      make it possible now to demonstrate the presence of fetal DNA in maternal plasma.
      These methods lying on non invasive procedures could advantageously be applied to
      the genotyping of fetal RHD during pregnancy. The present paper aims to discuss
      the predictive values of RHD fetal genotype in maternal plasma of RhD negative
      mothers. The ante-partum management of immunised pregnant women is reviewed in
      the light of this new molecular approach combined to Doppler ultrasonography of
      the fetal middle cerebral artery. This non invasive method for determining fetal
      RHD genotype could be systematically proposed to all RhD negative pregnant women
      for a better targeted prenatal follow-up and an increased efficacy of RhD
      prophylaxis.

PMID- 17191744
TI  - [Lumps and bumps. Diagnosis and management of soft-tissue tumors].
AB  - Patients with soft-tissue tumours usually consult for a mass at the level of an
      extremity or the torso. This article aims to help the general practitioner and
      the general surgeon in the standardized setup of these tumours. The epidemiology,
      clinical presentation and evaluation as well as the useful exams to be performed,
      including biopsy, are developped, in order to obtain rational principles for the
      diagnostic setup and surgical decision-making.

PMID- 17191745
TI  - [Surgical treatment of chest wall tumors].
AB  - The observation of a primary chest wall desmoid tumor discovered incidentally in
      a young patient is an opportunity to review the nosology, diagnosis and treatment
      of this uncommon pathology. Surgical intervention should aim at resecting
      completely the lesion with sufficient margins. Subsequent reconstruction of the
      bony thorax uses synthetic materials and muscle or myocutaneous flaps.

PMID- 17191746
TI  - [Massive hemoptysis: experience of a surgical unit].
AB  - Massive hemoptysis is a clinical entity characterized by its unpredictable and
      potential lethal course. We studied retrospectively the observations of 25
      patients hospitalized in our surgical unit. We collected all the demographic,
      clinical and surgical data. A male predominance with a sex-ratio of 2,1 was
      noted. The average age was 45 years, with extremes of 17 and 75. The dominant
      cause was bronchiectasis. Twenty patients were operated on. The surgery consisted
      of a pulmonary resection in 9 cases (45%), an atypical lung resection in 4 cases
      (20%), a resection of an aspergilloma in 2 cases (10%), a kystectomy of hydatic
      cyst in 4 cases (20%) and one arterial ligature (5%). Five patients (25%) had
      emergent surgery, and 15 (75%) delayed surgery. Hospital mortality was 20% in the
      first group and 6.66% in the second. No recurrence of bleeding was observed after
      an average follow-up of 7 months. Surgery remains a therapy of choice for massive
      hemopysis. It must as far as possible be avoided during active bleeding.

PMID- 17191747
TI  - [How I explore...cheilitis].
AB  - A cheilitis is an inflammatory disease confined to the lips. Several origins are
      recognized. Their nature is often different in children and adults. Some are
      spongiotic due to irritation or allergic reaction. Other lesions are keratotic
      and can evolve to leucoplasia and epidermoid carcinoma.

PMID- 17191748
TI  - [Ibandronate (Bonviva) in the treatment of postmenopausal osteoporosis].
AB  - Ibandronate is a nitrogen-containing bisphosphonate which has been shown to
      reduce vertebral fracture rates, when given orally either daily or
      intermittently. Non-vertebral antifracture efficacy of ibandronate has been
      derived from a post-hoc analysis focusing on patients at high risk of developing
      non-vertebral fractures (low bone mineral density at the femoral neck). Once
      monthly administration of oral ibandronate has been linked to significantly
      greater increases in bone mineral density, at the spine, hip and femoral neck,
      compared to daily formulation. This monthly formulation has a safety profile
      similar to the one observed with the daily administration of the compound.
      Adherence to monthly bisphosphonates appears to be significantly higher than for
      daily or weekly administration.

PMID- 17191749
TI  - [Medication of the month. Duloxetine (Cymbalta)].
AB  - Duloxetine (Cymbalta is an antidepressant of the class of serotonin noradrenaline
      reuptake inhibitors. The efficacy of duloxetine 60 mg/day has been well
      demonstrated in the acute and long term treatment of major depression. The level
      of effectiveness of duloxetine is particularly high and associated with a shorter
      latency of action. Duloxetine also exhibits antinociceptive properties
      independently of the antidepressant effect. The side-effect profile of duloxetine
      is particularly good and similar to selective serotonin reuptake inhibitors with
      mainly nausea. In total, duloxetine represents a real progress in the
      pharmacological treatment of major depression.

PMID- 17191750
TI  - Are low levels of specific IGE useful in diagnosing clinically relevant food
      sensitization?

PMID- 17191751
TI  - Safety, tolerability and efficacy of sublingual allergoid immunotherapy with a 4
      day shortened build-up phase.
AB  - BACKGROUND: Sublingual specific immunotherapy (SLIT) with monomeric allergoid has
      shown to be safe and effective the studies performed so far. The build-up phase,
      however, is rather time consuming mainly if performed with the conventional
      schedule of 14 weeks. AIMS OF STUDY: We evaluated the possibility of shortening
      and simplifying this phase, through a new build-up scheme of only 4 days, as well
      as the persistence of the allergoid SLIT efficacy after 12 months. METHODS:
      Thirty-nine patients (26 M, 13 F, mean age 20.5 years, range 6-49) with a history
      of moderate/severe rhinitis with or without mild asthma due to perennial and/or
      seasonal allergens entered the study. The posological schedule, adopting only
      1,000 AU tablets, was the following: 1/2 tablet the 1st day; 1/2 table twice the
      second day; 1/2 table plus 1 table the 3rd day, 1 tablet twice the 4th day; 1
      tablet twice weekly from the 5th to the 365th day (maintenance therapy). RESULTS:
      Only two mild adverse reactions occurred during the initial phase which
      disappeared with the prosecution of the treatment. During the maintenance therapy
      no adverse event was observed. Symptoms improved consistently and drug
      consumption was reduced in most of the patients. CONCLUSIONS: The 4-day shortened
      build-up phase resulted to be safe, well tolerated and effective, already after
      one year of treatment.

PMID- 17191753
TI  - Do conditional reinforcers count?
AB  - Six pigeons were trained on a procedure in which seven components arranged
      different food-delivery ratios on concurrent variable-interval schedules each
      session. The components were unsignaled, lasted for 10 food deliveries, and
      occurred in random order with a 60-s blackout between components. The schedules
      were arranged using a switching-key procedure in which two responses on a center
      key changed the schedules and associated stimuli on two side keys. In Experiment
      1, over five conditions, an increasing proportion of food deliveries accompanied
      by a magazine light was replaced with the presentation of the magazine light
      only. Local analyses of preference showed preference pulses toward the
      alternative that had just produced either a food-plus-magazine-light or magazine
      light-only presentation, but pulses after food deliveries were always greater
      than those after magazine lights. Increasing proportions of magazine lights did
      not change the size of preference pulses after food or magazine-light
      presentations. Experiment 2 investigated the effects of correlations between food
      ratios and magazine-light ratios: In Condition 6, magazine-light ratios in
      components were inversely correlated (-1.0) with food ratios, and in Condition 7,
      magazine-light ratios were uncorrelated with food ratios. In Conditions 8 and 9,
      pecks also produced occasional 2.5-s flashes of a green keylight. In Condition 8,
      food and magazine-light ratios were correlated 1.0 whereas food and green-key
      ratios were correlated -1.0. In Condition 9, food and green-key ratios were
      correlated 1.0 whereas food and magazine-light ratios were correlated -1.0.
      Preference pulses toward alternatives after magazine lights and green keys
      depended on the correlation between these event ratios and the food ratios: If
      the ratios were correlated +1.0, positive preference pulses resulted; if the
      correlation was -1.0, preference pulses were negative. These results suggest that
      the Law of Effect has more to do with events signaling consequences than with
      strengthening responses.

PMID- 17191752
TI  - Survey on the safety of a no-updosing regimen of sublingual immunotherapy.

PMID- 17191754
TI  - Effects of D-amphetamine and ethanol on variable and repetitive key-peck
      sequences in pigeons.
AB  - This experiment assessed the effects of d-amphetamine and ethanol on reinforced
      variable and repetitive key-peck sequences in pigeons. Pigeons responded on two
      keys under a multiple schedule of Repeat and Vary components. In the Repeat
      component, completion of a target sequence of right, right, left, left resulted
      in food. In the Vary component, 4-peck sequences differing from the previous 10
      produced food. d-Amphetamine (0.1-3.0 mg/kg, i.m.) was administered in two
      separate phases, separated by ethanol administration (1.0-2.0 g/kg, i.g.). Under
      control conditions, measures of variability were high in the Vary component, and
      lower in the Repeat component. Following administration of the highest dose of d
      amphetamine, but not ethanol, response rates decreased in both components. d
      Amphetamine and ethanol tended to increase overall sequence variability in the
      Repeat component, and had less of an effect in the Vary component. Performance in
      the Repeat component during Phase 2 of d-amphetamine administration was more
      disrupted than during Phase 1. Measures of variability and repetition based on
      shifts in the relative frequency distributions of the 16 possible keypeck
      sequences differed from those based on the overall measure of variability,
      highlighting the importance of considering both molar and molecular measures when
      assessing the effects of drugs on reinforced variability and repetition. In
      addition, the shifts in the relative frequency distribution of response sequences
      suggest that d-amphetamine produced decrements in repeat performance by
      decreasing discriminative control within response sequences, whereas ethanol
      decreased repeat performance by decreasing discriminability between components as
      well as discriminative control within response sequences.

PMID- 17191755
TI  - Resurgence of response sequences during extinction in rats shows a primacy
      effect.
AB  - Rats were trained to emit a series of three-response sequences to a criterion
      (i.e., more than 80% of all emitted sequences correct over five successive
      sessions). Each rat was trained on a series of different, three-response
      sequences. After the final three-response sequence was acquired, two extinction
      tests were administered, and the three-response sequences that re-emerged during
      these extinction tests were noted. Resurgence effects during extinction were
      observed; that is, the previously trained sequences were emitted. These
      resurgence effects followed an orderly pattern, which involved a primacy effect.
      The rats initially emitted the immediately previously trained response, but then
      started to emit the response sequence they first were trained to emit. Thus,
      resurgence behavior during extinction can be an orderly function of previous
      training history. These results replicate those previously obtained with human
      subjects.

PMID- 17191756
TI  - The transformation of consequential functions in accordance with the relational
      frames of more-than and less-than.
AB  - Across three experiments, the transformation of consequential functions in
      accordance with a seven-member relational network (A-B-C-D-E-F-G) was
      investigated. In this network, the relational rankings ranged from A, ranked the
      least, to G, ranked the most. In the first phase, contextual cues for more-than
      and less-than were established by training participants across multiple exemplars
      to select comparisons containing larger quantities in the presence of the former
      cue, and fewer quantities in the presence of the latter cue. Participants then
      were trained in six conditional discriminations (i.e., A<B, B<C, C<D, E>D, F>E,
      and G>F) with the contextual cues as samples and nonsense words as comparisons,
      and all possible derived relations were tested (e.g., B<F). In a subsequent
      phase, the D stimulus was paired with the delivery of points. Next, a test for a
      transformation of consequential functions was presented in either simultaneous
      discrimination tasks (Experiments 1 and 2) or a free-operant schedule task
      (Experiment 3), each of which employed members of the relational network as
      consequences. In all experiments, participants consistently emitted the response
      that produced the derived consequential stimulus that was ranked higher in the
      relational network, thus demonstrating a transformation of consequential
      functions. In Experiment 2, the baseline conditional discriminations were altered
      in a reversal design, and Experiment 3 examined generalization of the derived
      performance to a schedule-based task, with and without detailed instructions.
      Overall, the study demonstrated a transformation and generalization of
      consequential functions in accordance with the relational frames of More-than and
      Less-than, and bears relevance to the literature on transitive inference.

PMID- 17191757
TI  - Equivalence relations, contextual control, and naming.
AB  - This paper reports two experiments that investigated the role of verbal behavior
      in the emergence and generalization of contextually controlled equivalence
      classes. During both experiments, participants were trained with two different
      combinations of the same easily nameable, yet formally unrelated, pictorial
      stimuli. Match-to-sample baselines for eight four-member classes were established
      under the contextual control of two colors. In the presence of one color,
      conditional relations were established between stimuli whose normative names
      rhymed. In the presence of the other color, conditional relations were
      established between stimuli whose normative names did not rhyme. Although, during
      Experiment 1, all participants demonstrated equivalence classes involving rhyming
      stimuli, none demonstrated the formation of nonrhyme equivalence classes. To
      investigate this finding, Experiment 2 evaluated whether participants would
      demonstrate both rhyme and nonrhyme equivalence classes given more extensive
      exposure to the experimental contingencies. All participants demonstrated
      contextually controlled rhyme and nonrhyme equivalence classes, although rhyme
      classes were demonstrated with greater facility than nonrhyme classes. Results
      indicate that visual stimuli are named, that verbal bases for stimulus
      classification can affect the emergence of contextually controlled equivalence
      classes, and that untrained contextually controlled conditional discriminations
      involving novel stimuli can emerge on the basis of participants' verbal behavior.

PMID- 17191758
TI  - A major trio.

PMID- 17191759
TI  - Behavioral determinants of drug action. The contributions of Peter B. Dews.
AB  - Peter B. Dews played a significant role in shaping the distinctive
      characteristics and defining the underlying principles of the discipline of
      behavioral pharmacology. His early and sophisticated use of schedules of
      reinforcement in the 1950s, incorporated from research in the experimental
      analysis of behavior and integrated into the discipline of pharmacology, provided
      tremendous insight, inspiration, and impetus to the newly emerging field of
      behavioral pharmacology. The experimental findings generated by Dews' research,
      blending the sophisticated use of behavior and pharmacological principles
      together with the elegant manner of their presentation and far-reaching
      implications, provided the force and momentum to establish and direct behavioral
      pharmacology for several decades. This article attempts to capture some of Dews'
      research that integrated and inspired the blending of sophisticated behavioral
      work with that of pharmacology.

PMID- 17191760
TI  - Roger T. Kelleher, behavior analyst.
AB  - Roger T. Kelleher, rightly known as one of the foremost contributors to
      behavioral pharmacology, also made many important contributions to the
      experimental analysis of behavior. He participated significantly in the
      development of the discipline, through both his research and his editorial
      contributions to thisjournal. This article summarizes his contributions to the
      field of behavior analysis. His most significant empirical and conceptual
      contributions to behavior analysis came in two domains-conditioned reinforcement
      and the power of schedules of reinforcement. His accomplishments in these two
      domains still serve as principal foundations for modern research and theory.

PMID- 17191761
TI  - An architect of the golden years.
AB  - William H. Morse has played a major role in the experimental analysis of
      behavior. His view of operant behavior as the outcome of differential
      reinforcement provides an invaluable lesson in scientific research and theory. He
      studied schedules of reinforcement to generate an in-depth analysis of the
      complex interactions existing when contingencies exert their control over
      behavior. He has been instrumental in showing how behavior is determined by the
      dynamic interaction of factors brought into play by the imposition of any
      schedule, and he has a remarkably intuitive understanding of the nature of these
      determining variables. Some of these causal events are imposed directly by the
      schedule, but others arise in a more indirect manner through necessary
      constraints. In Morse's view, schedules can be more fundamental in determining
      behavior than are the scheduled events themselves. Behavior is the shaped product
      of an organism's history in combination with present environmental conditions.
      His impact deserves to be more than historical: A study of his work continues to
      reward the reader with exciting insights into the nature of behavioral control.

PMID- 17191762
TI  - Stability of pigeon body weight under free-feeding conditions.
AB  - Increases in regulatory oversight of animal research require verification of
      effects of standard practices. There are no formal guidelines for establishing
      free-feeding weights in adult pigeons. In the present study, pigeons were
      obtained from a commercial supplier, weighed upon arrival, and then held in
      quarantine for 7 days with free access to food. Subsequently, still with
      continuous access to food, they were weighed daily for 30 days. No significant
      changes in weights occurred over the 30-day period for male pigeons, indicating
      that seven days is sufficient for establishing a baseline body weight. A
      secondary finding of higher day-to-day variability in the weights of female
      pigeons may serve as a method of sexing pigeons.

PMID- 17191764
TI  - Imaging of the lymphatic system: new horizons.
AB  - The lymphatic system is a complex network of lymph vessels, lymphatic organs and
      lymph nodes. Traditionally, imaging of the lymphatic system has been based on
      conventional imaging methods like computed tomography (CT) and magnetic resonance
      imaging (MRI), whereby enlargement of lymph nodes is considered the primary
      diagnostic criterion for disease. This is particularly true in oncology, where
      nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI
      on their own are, however, anatomical imaging methods. Newer imaging methods such
      as positron emission tomography (PET), dynamic contrast-enhanced MRI (DCE-MRI)
      and color Doppler ultrasound (CDUS) provide a functional assessment of node
      status. None of these techniques is capable of detecting flow within the
      lymphatics and, thus, several intra-lymphatic imaging methods have been
      developed. Direct lymphangiography is an all-but-extinct method of visualizing
      the lymphatic drainage from an extremity using oil-based iodine contrast agents.
      More recently, interstitially injected intra-lymphatic imaging, such as
      lymphoscintigraphy, has been used for lymphedema assessment and sentinel node
      detection. Nevertheless, radionuclide-based imaging has the disadvantage of poor
      resolution. This has lead to the development of novel systemic and interstitial
      imaging techniques which are minimally invasive and have the potential to provide
      both structural and functional information; this is a particular advantage for
      cancer imaging, where anatomical depiction alone often provides insufficient
      information. At present the respective role each modality plays remains to be
      determined. Indeed, multi-modal imaging may be more appropriate for certain
      lymphatic disorders. The field of lymphatic imaging is ever evolving, and
      technological advances, combined with the development of new contrast agents,
      continue to improve diagnostic accuracy.

PMID- 17191765
TI  - Targeting of lanthanide(III) chelates of DOTA-type glycoconjugates to the hepatic
      asyaloglycoprotein receptor: cell internalization and animal imaging studies.
AB  - The characterization of a new class of hydrophilic liver-targeted agents for
      gamma-scintigraphy and MRI, consisting, respectively, of [(153)Sm](3+) or Gd(3+)
      complexes of DOTA monoamide or bisamide linked glycoconjugates (DOTA = 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid), is reported. In vitro studies
      show high uptake of radiolabeled [(153)Sm]-DOTAGal(2) by the human hepatocyte
      carcinoma cell line Hep G2 containing the asialoglycoprotein receptor (ASGP-R),
      which is decreased to less than 50% by the presence of its high-affinity ligand
      asialofetuin (ASF). In vivo biodistribution, gamma-imaging and pharmacokinetic
      studies on Wistar rats using the [(153)Sm](3+)-labeled glycoconjugates show a
      high uptake in the receptor-rich organ liver of the radiolabeled compounds
      containing terminal galactosyl groups, but very little uptake for those compounds
      with terminal glycosyl groups. Blocking the receptor in vivo reduced liver uptake
      by 90%, strongly suggesting that the liver uptake of these compounds is mediated
      by their binding to the asyaloglycoprotein receptor (ASGP-R). This study also
      demonstrated that the valency increase improves the targeting capability of the
      glycoconjugates, which is also affected by their topology. However despite the
      specific liver uptake of the radiolabeled galactose-bearing multivalent
      compounds, the animal MRI assessment of the corresponding Gd(3+) chelates shows
      liver-to-kidney contrast effects which are not significantly better than those
      shown by GdDTPA. This probably results from the quick wash-out from the liver of
      these highly hydrophilic complexes, before they can be sufficiently concentrated
      within the hepatocytes via receptor-mediated endocytosis.

PMID- 17191766
TI  - Targeted ultrasound contrast agent for molecular imaging of inflammation in high
      shear flow.
AB  - Targeted ultrasound contrast materials (gas-filled microbubbles carrying ligands
      to endothelial selectins or integrins) have been investigated as potential
      molecular imaging agents. Such microbubbles normally exhibit good targeting
      capability at the slower flow conditions. However, in the conditions of vigorous
      flow, binding may be limited. Here, we describe a microbubble capable of
      efficient binding to targets both in slow and fast flow (exceeding 4 dyne/cm(2)
      wall shear stress) using a clustered polymeric form of the fast-binding selectin
      ligand sialyl Lewis(X). Microbubbles were prepared from decafluorobutane gas and
      stabilized with a monolayer of phosphatidylcholine, PEG stearate and biotin-PEG
      lipid. Biotinylated PSLe(x) (sialyl Lewis(X) polyacrylamide) or biotinylated anti
      P-selectin antibody (RB40.34) was attached to microbubbles via a streptavidin
      bridge. In a parallel plate flow chamber targeted adhesion model, PSLe(x) bubbles
      demonstrated specific adhesion, retention and slow rolling on P-selectin-coated
      plates. Efficiency of firm targeted adhesion to a P-selectin surface (140
      molecules/microm(2)) was comparable for antibody-carrying bubbles and PSLe(x)
      targeted bubbles at 0.68 dyne/cm(2) shear stress. At fast flow (4.45 dyne/cm(2)),
      PSLe(x)-targeted bubbles maintained their ability to bind, while antibody
      mediated targeting dropped more than 20-fold. At lower surface density of P
      selectin (7 molecules/microm(2)), targeting via PSLe(x) was more efficient than
      via antibody under all the flow conditions tested. Negative control casein-coated
      plates did not retain bubbles in the range of flow conditions studied. To confirm
      echogenicity, targeted PSLe(x)-bubbles were visualized on P-selectin-coated
      polystyrene plates by ultrasound imaging with a clinical scanner operated in
      pulse inversion mode; control plates lacking targeted bubbles did not show
      significant acoustic backscatter. In vivo, in a murine model of inflammation in
      the femoral vein setting, targeting efficacy of intravenously administered
      PSLe(x)-microbubbles was comparable with targeting mediated by anti-P-selectin
      antibody, and significantly exceeded the accumulation of non-targeted control
      bubbles. In the inflamed femoral artery setting, PSLe(x)-mediated microbubble
      targeting was superior to antibody-mediated targeting.

PMID- 17191767
TI  - Pharmacokinetic and in vivo evaluation of a self-assembled gadolinium(III)
      iron(II) contrast agent with high relaxivity.
AB  - A high-molecular weight tetrametallic supramolecular complex [(Ln-DTPA-phen)3Fe]-
      (Ln = Gd, Eu, La) has been obtained upon self-assembly around one iron(II) ion of
      three 1,10-phenantroline-based molecules substituted in 5'-position with the
      polyaminocarboxylate diethylenetriamine-N,N,N',N',N'-pentaacetate, DTPA-phen(4-).
      The ICP-MS measurements indicated that the lanthanide:iron ratio is 3:1.
      Photoluminescence spectra of [Eu-DTPA-phen](-) and of [(Eu-DTPA-phen)3Fe]- are
      nearly identical, implying that the first coordination sphere of the
      lanthanide(III) ion has not been changed upon coordination of phenantroline unit
      to iron(II) ion. NMRD measurements revealed that at 20 MHz and 310 K the
      relaxivity of the [(Gd-DTPA-phen)3Fe]- is equal to 9.5 +/- 0.3 s(-1) mM(-1) of Gd
      (28.5 s(-1) per millimole per liter of complex) which is significantly higher
      than that for Gd-DTPA (3.9 s(-1) mM(-1)). The pharmacokinetic parameters of [(Gd
      DTPA-phen)3Fe]- in rats indicate that the elimination of [(Gd-DTPA-phen)3Fe]- is
      significantly slower than that of Gd-DTPA and is correlated with a reduced volume
      of distribution. The low volume of distribution and the longer elimination time
      (T(e1/2)) suggest that the agent is confined to the blood compartment, so it
      could have an important potential as a blood pool contrast agent. The
      biodistribution profile of [(Gd-DTPA-phen)3Fe]- 2 h after injection indicates
      significantly higher concentrations of [(Gd-DTPA-phen)3Fe]- as compared with Gd
      DTPA in kidney, liver, lungs, heart and spleen. The images obtained on rats by MR
      angiography show the enhancement of the abdominal blood vessels. The signal
      intensity reaches a maximum of 55% at 7 min post-contrast and remains around 25%
      after 90 min. MRI-histomorphological correlation studies of [Gd-DTPA-phen]- and
      [(Gd-DTPA-phen)3Fe]- showed that both agents displayed potent contrast
      enhancement in organs including the liver. The necrosis avidity tests indicated
      that, in contrast to the [Gd-DTPA-phen](-) precursor complex, the supramolecular
      complex [(Gd-DTPA-phen)3Fe]- exhibits necrosis avidity.

PMID- 17191768
TI  - Characterization of the in vitro adherence behavior of ultrasound responsive
      double-shelled microspheres targeted to cellular adhesion molecules.
AB  - We have developed novel adhesion molecule-targeted double-shelled microspheres
      which encapsulate nitrogen. We report in vitro targeting studies utilizing these
      microspheres conjugated to target-specific antibodies directed towards ICAM-1 and
      VCAM-1. In static adherence experiments, the adherence patterns of microspheres
      conjugated to three different monoclonal antibodies (two targeted to ICAM-1 and
      one to VCAM-1) to their target surfaces were very different. Maximum microsphere
      adherence at the lowest target and/or ligand densities was observed with the VCAM
      1 system. Differences in target-specific adherence were also observed between
      anti-ICAM-1 and anti-VCAM-1 microsphere conjugates in flow adherence studies.
      Equilibrium binding studies of the target proteins in solution to the microsphere
      bound ligands showed that the affinity constants of two microsphere-bound
      monoclonal antibodies for their target proteins are similar. Thus, ligand-target
      affinity is not the only determinant of microsphere adherence to the target
      surface in our systems. Shear stress was found to have an effect on the mean
      diameter of adhered microspheres; a decrease in the mean diameter with increasing
      shear was observed. The magnitude of this effect was dependent on both
      microsphere-bound ligand and target surface densities, with a more pronounced
      change at lower densities. Adhered microspheres were readily detectable using
      ultrasound at the lowest tested surface density of 40 mm(-2).

PMID- 17191773
TI  - Vanishing flora--lost chemistry: the scents of endangered plants around the
      world.
AB  - As part of our broad and ongoing evaluation of the olfactory components of
      fragrant plants and flowers during the past 25 years, we have encountered an
      astounding number of interestingly scented, but endangered plant species. In
      appreciation of nature's marvels in these species, we are compiling a report on
      their scent compositions and complementary information in an upcoming book
      'Vanishing Flora--Lost Chemistry'. In this paper, a few examples of endangered
      plant species and their scent components are presented as a brief introduction to
      the concept of the book project.

PMID- 17191774
TI  - Polarized vesicles in molecular recognition and catalysis.
AB  - This account summarizes studies on chemistry in polarized vesicles with rigid-rod
      molecules. Examples for the recognition of and self-assembly, molecular
      recognition, and catalysis in polarized vesicles are discussed with emphasis on
      'remote control' by dipole-potential interactions and electrostatic steering.

PMID- 17191775
TI  - Non-nucleoside reverse transcriptase inhibitors (NNRTIs): past, present, and
      future.
AB  - Non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) have become an
      inherent ingredient of the drug combination schemes that are currently used in
      the treatment of human immunodeficiency virus type 1 (HIV-1) infections. Starting
      from the 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 4,5,6,7
      tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO)
      derivatives, numerous classes of compounds have been described as NNRTIs. Only
      three compounds have so far been approved for clinical use: nevirapine,
      delavirdine, and efavirenz. NNRTIs are notorious for rapidly leading to virus
      drug resistance development, primarily based on the emergence of the K103N and
      Y181C mutations in the HIV-1 RT. Newer NNRTIs, such as capravirine, dapivirine
      (TMC 125), and DPC 083, are resilient to these 'NNRTI' mutations, and, therefore,
      offer considerable promise as future anti-HIV-1 drugs. NNRTIs are targeted at a
      specific 'pocket' binding site within the HIV-1 RT, that is distinct from, but
      both spatially and functionally related to, the catalytic site, where the
      nucleoside RT inhibitors (NRTIs) and nucleotide RT inhibitors (NtRTIs) interact.
      NNRTIs have acquired a definitive position, as part of a combination regimen with
      NRTIs and NtRTIs, in the first-line treatment of HIV-1 infections.

PMID- 17191776
TI  - Chemical and biological investigations of beta-oligoarginines.
AB  - In view of the important role arginine plays in living organisms as the free
      amino acid and, especially, as a residue in peptides and proteins, the homologous
      beta-homoarginines are central in our investigations of beta-peptides (Fig. 1).
      The preparation of beta2-homoarginine derivatives suitably protected for solution
      or solid-phase peptide syntheses is described with full experimental detail (9
      and 12 in Scheme 1). The readily available Fmoc-beta3 hArg(Boc)2-OH is used for
      manual solid-phase synthesis of beta3-oligoarginines (on Rink amide or Rink amide
      AM resin) either by single amino acid coupling (Scheme 3) or, much better, by
      dimer-fragment coupling (Scheme 4). In this way, beta3-oligoarginine amides
      composed of 4, 6, 7, 8, and 10 residues, both with and without fluorescein
      labelling, were synthesized (Schemes 2-4), purified by preparative HPLC and
      identified by high-resolution mass spectrometry. The free amino acids (R)- and
      (S)-H-beta2 hArg-OH and (S)-H-beta3 hArg-OH were tested for their ability to
      function as substrates for NO synthase (iNOS); the beta3-oligoarginine amides (5,
      6, and 7 residues) were tested for antibacterial (against six pathogens) and
      hemolytic (against rat and human erythrocytes) activities. All test results were
      negative: none of the free beta-homoarginines induced NO formation (Fig. 3), and
      there was no lysis of erythrocytes (concentrations up to 100 microM; Table 1),
      and no significant antibiotic activity (MIC > or = 64 microg/ml; Table 2). Cell
      penetration studies with the fluorescence-labelled, peptidase-resistant beta3
      oligoarginine amides were carried out with HeLa cells and human foreskin
      keratinocytes (HFKs). The results obtained with fluorescence microscopy are: i)
      the longer-chain beta-oligoarginine amides (8 and 10 residues; Figs. 4-6) enter
      the cells and end up in the nuclei, especially in the nucleoli, irrespective of
      temperature (37 degrees and 4 degrees with HFKs) or pretreatment with NaN3 (with
      HFKs), indicating a non-endocytotic and non-energy-dependent uptake mechanism;
      ii) the beta-tetraarginine derivative occupies the cell surface but does not
      enter the cells (with HeLa); iii) the cell-growth rate of the HFKs is not
      affected by a 1-microM concentration of the fluorescence-labelled beta
      octaarginine amide (Fig. 7), i.e., there is no antiproliferative effect. In vivo
      experiments with mouse skin and the beta-octaarginine derivative show migration
      of the beta-peptide throughout the epidermis (Fig. 8). As a contribution to
      understanding the mechanism, we have also studied the behavior of fluorescence
      labelled beta-octa- and beta-decaarginine amides (TFA salts) towards giant
      unilamellar vesicles (GUVs) built of neutral (POPC) or anionic (POPC/POPG
      mixtures) phospholipids: the beta-oligoarginine amides bind tightly to the
      surface of anionic GUVs but do not penetrate the lipid bilayer (Fig. 9) as they
      do with living cells. In contrast, a beta-heptapeptide FL-22, which had been used
      as a negative control sample for the cell-penetration experiments, entered the
      GUVs of negative surface charge. Thus, the mechanisms of cell and GUV-model
      penetration appear to be different. Finally, the possible applications and
      implications of the 'protein transduction' by beta-oligoarginines are discussed.

PMID- 17191777
TI  - The importance of being exhaustive. Optimization of bridging structural water
      molecules and water networks in models of biological systems.
AB  - Algorithms and protocols are described for the optimization for H-bonding of
      isolated singular H2O molecules and entire networks of H2O molecules. Unlike
      other approaches that are prone to being trapped in local energy minima, these
      methods rely on exhaustive searches of orientation space for the H2O molecules.
      The results are scored with the HINT hydropathic interaction model, but the
      algorithms should be general for any energy-scoring computation. Two examples are
      provided: 1) the tightly-bound H2O molecule 301 of HIV-1 protease is shown to be
      more reasonably oriented in terms of forming H-bonds with this method than with a
      molecular mechanics energy minimization method; and 2) the H2O network
      surrounding carbonmonoxymyoglobin is constructed and analyzed for a 1.80-A
      neutron-diffraction structure. The H-atom positions calculated with this method
      show a somewhat better agreement with the experimental results than do the H-atom
      positions calculated with molecular mechanics, and both are considerably better
      than random.

PMID- 17191778
TI  - One-step synthesis of hypoxanthine from glycinamide and diformylurea.
AB  - Because of their easy availability and their relative chemical stability, urea,
      formic acid, and glycine might have played a role in the assembly process of
      nucleobases. In this paper, a short reaction path is described to prepare
      hypoxanthine starting from the above mentioned precursors. The formation of
      hypoxanthine has been verified by high-resolution mass spectrometry with the 15N
      labelled urea as starting material, and HPLC analysis. The yield of this
      condensation reaction has been determined spectrophotometrically.

PMID- 17191780
TI  - A novel type of membranes based on cholesteryl phosphate.
AB  - Mixtures of the rigid amphiphile disodium cholesteryl phosphate (DCP) with the
      non-phosphorylated diacyl amphiphile dimyristoylglycerol (DMG) give self
      organized systems in a wide range of pH, as demonstrated by differential
      microcalorimetry. These systems can be closed bilayer vesicles, as shown by
      optical microscopy (Nomarski and confocal). Neither DMG nor DCP, taken alone,
      give vesicles in these conditions but 10% DMG is enough to lead to the formation
      of vesicles from pH 5.8 to 9.3. These novel self-organized systems are akin to
      the classical eucaryotic ones, built on a phosphorylated diacylglycerol and free
      cholesterol (or analogues), the only difference being the site of the phosphate
      head-group.

PMID- 17191779
TI  - Influence of threose nucleoside units on the catalytic activity of a hammerhead
      ribozyme.
AB  - TNA (alpha-L-threose nucleic acids) is potentially a natural nucleic acid, that
      might have acted as an evolutionary alternative of RNA. We determined the
      catalytic activity of hammerhead ribozymes containing a threofuranosyl-modified
      nucleoside at position U4 and U7, and compared these results with those obtained
      from HNA (hexitol nucleic acids) insertion into the same ribozyme. Our
      experiments showed that, although the threofuranosyl-modified ribozymes still
      cleave the substrate strand, cleavage activity is highly decreased. It,
      therefore, seems that TNA can play a functional role in the RNA world, but only
      to a limited extent.

PMID- 17191781
TI  - The first chemical synthesis of a cyclodextrin heteroduplex.
AB  - The synthesis of the first heteroduplex of cyclodextrin (CD) 11, i.e., a compound
      in which the two primary rims of alpha- and beta-CDs are doubly connected, was
      achieved. The selected strategy involved a Sonogashira coupling of propargylated
      beta-CD 6 and iodo-alkenyl alpha-CD 4 to singly connect the two CDs. A ring
      closing metathesis (RCM) of the heterodimer 9 afforded the second bridge, final
      deprotection and reductions giving access to 11.

PMID- 17191782
TI  - Bioisosterism: quantitation of structure and property effects.
AB  - The powerful concept of bioisosterism is presented as a method for selecting
      molecular groups for drug design and lead-compound development. Three group
      structure characteristics are described for this purpose. The E-State value for
      an attached atom is used as a measure of electrotopological group impact. The
      volume of the group is estimated from counts of sigma, pi, and lone-pair n
      electrons, as embodied in the valence and simple connectivity delta values for
      atoms in the group. Polarity is described in terms of the polarity index Q(v).
      Specific examples are given for commonly used groups. Parameter spaces encoding
      these three attributes are presented as examples that may be used to guide
      bioisostere selection in late-stage drug-design procedures. The method presented
      here is of practical value in the decision processes of molecular modification.

PMID- 17191783
TI  - Effect of the secondary structure of carbohydrate residues of alpha 1-acid
      glycoprotein (orosomucoid) on the local dynamics of Trp residues.
AB  - We studied in this work the relation between the secondary structure of the
      carbohydrate residues of alpha1-acid glycoprotein and the local motions of Trp
      residues of the protein. We measured for this purpose the fluorescence emission
      intensity and anisotropy of the Trp residues between -46 and +30 degrees of the
      sialylated and asialylated protein. Our results indicate that, in both forms, the
      global profile of the emission intensity with temperature shows that Trp residues
      display static and collisional interaction with the neighboring amino acids.
      However, the profile of the asialylated form is more structured than that
      observed for the sialylated protein. The Y-plot analysis of the emission
      anisotropy results indicated that the frictional resistance to rotation of the
      surface Trp residue is less important in the sialylated protein than in the
      asialylated form. This result is in good agreement with the fact that, in the
      asialylated conformation, the carbohydrate residues are closer to the protein
      surface than in the sialylated form, thereby increasing the contact of the
      surface Trp residue with the neighboring amino acids. Also, the interaction
      between the carbohydrate residues and the surface Trp residue contributes to the
      modification of the frictional resistance to rotation of the fluorophore.

PMID- 17191784
TI  - TMC-95A analogues with endocyclic biphenyl ether group as proteasome inhibitors.
AB  - TMC-95A, a cyclic tripeptide metabolite of Apiospora montagnei, is a potent
      competitive inhibitor of proteasome. Based on the X-ray structure of its complex
      with yeast proteasome, the synthetically challenging structure of this natural
      product was simplified in a first generation of analogues by replacing the highly
      oxidized side-chain biaryl system with a phenyl-oxindole group. In the present
      study, the TMC-95 biaryl group was substituted with a biphenyl ether with
      retainment of significant proteasome inhibition. Because of the facile synthetic
      access of tripeptides containing in i, i+2 positions residues of the
      isodityrosine type, this new generation of TMC-95 analogues may represent
      promising lead structures for further optimization of affinity and selectivity of
      proteasome inhibitors.

PMID- 17191785
TI  - The elusive indigo precursors in woad (Isatis tinctoria L.)--identification of
      the major indigo precursor, isatan A, and a structure revision of isatan B.
AB  - A metabolite-profiling study of shock-frozen leaves of Isatis tinctoria L., an
      old indigo dye plant and medicinal herb, revealed a complex pattern of indigo
      forming compounds with higher polarities than the known indigo precursors isatan
      B and indican. These highly unstable compounds underwent rapid post-harvest
      transformation and were not detected in air-dried leaves. The major indigo
      precursor, named isatan A (4), was isolated by rapid normal-phase and gel
      chromatography, along with isatan B (3). A full spectral data set of 3 showed
      that the previous structure assignment as 'indoxyl-5-ketogluconate' has to be
      revised to 1H-indol-3-yl beta-D-ribohex-3-ulopyranoside. Isatan A (4) was
      identified as 1H-indol-3-yl 6'-O-(carboxyacetyl)-beta-D-ribohex-3'-ulopyranoside.
      In aqueous solution, glycosides 3 and 4 occur as hydrates and undergo rapid
      hydrolysis under very mild acidic or basic conditions.

PMID- 17191786
TI  - A structure-information approach to the prediction of biological activities and
      properties.
AB  - The structure-information approach to quantitative biological modeling and
      prediction is presented in contrast to the mechanism-based approach. Basic
      structure information is developed from the chemical graph (connection table).
      The development, beginning with information explicit in the connection table
      (element identity and skeletal connections), leads to significant structure
      information useful for establishing sound models of a wide range of properties of
      interest in drug design. Skeletal branching patterns and valence state definition
      lead to relationships for valence-state electronegativity and atom or group molar
      volumes. Based on these important aspects of molecules, both the
      electrotopological state (E-State) and molecular-connectivity structure
      descriptors (chi indices) are developed. A summary of QSAR models indicates the
      wide range of applicability of these structure descriptors and the predictive
      quality of QSAR models for protein binding, HIV-1 protease inhibition, blood
      brain-barrier partitioning, fish toxicity, carcinogenicity risk, structure space
      for similarity searching, and data mining. These models are independent of three
      dimensional structure information and are directly interpretable in terms of
      structure information useful to the drug-design process.

PMID- 17191787
TI  - Synthesis and applications of oligonucleotide-carbohydrate conjugates.
AB  - Nowadays, oligonucleotide-carbohydrate conjugates are used in antisense
      biotechnology and in the study of glycosylated DNA functioning in vitro. The
      application of mono- and disaccharide phosphoramidites, solid-phase supports with
      immobilized carbohydrates, glycosylated nucleoside phosphoramidites, and
      postsynthetic conjugation of reactive sugar derivatives with oligonucleotides for
      preparation of oligonucleotide-carbohydrate conjugates have been systematically
      studied. The advantages and disadvantages of these approaches are considered.
      Possible strategies for synthesis of glycoclusters with different topologies
      conjugated to DNA are discussed. Applications of oligonucleotide-carbohydrate
      conjugates are highlighted. Studies of interactions of glycosylated
      oligonucleotides with proteins and effective cell-specific delivery of
      oligonucleotide-carbohydrate conjugates are discussed.

PMID- 17191788
TI  - Exploratory studies to investigate a linked prebiotic origin of RNA and coded
      peptides. 2nd communication. Derivation and reactivity of xylose phosphates.
AB  - The potentially prebiotic synthesis of ribo-nucleotides by stepwise pyrimidine
      nucleobase assembly on arabinose-3-phosphate derivatives has been demonstrated in
      previous work. Consideration of the provenance of pentose phosphates, by
      aldolisation or sugar phosphorylation, suggested that 2-phosphate derivatives
      might be generated more easily than 3-phosphate derivatives. In the 2-phosphate
      series, nucleobase-assembly chemistry to give ribo-nucleotides/nucleic acid can
      be envisaged from xylo-configured starting materials. In this paper, the
      derivation of xylose-2-phosphate derivatives by aldol chemistry and attempts to
      demonstrate subsequent pyrimidine nucleobase assembly are reported.

PMID- 17191789
TI  - Stereo- and biochemical profiles of the 5-6- and 6-6-junction isomers of alpha-D
      mannopyranosyl [60]fullerenes.
AB  - The 5-6- and 6-6-junction isomers of alpha-D-mannopyranosyl [60]fullerene were
      studied by means of circular dichroism (CD), deuterium labeling, 1H-NMR,
      molecular-dynamics (MD) calculations, and a lectin-binding assay. The CD spectra
      of the O-acetylated derivatives allowed clear discrimination of the isomers,
      while the 1H-NMR spectra, with assistance from deuterium labeling and MD
      calculations, served to disclose the unique conformation and molecular geometry
      of each acetylated isomer in chloroform solution. The deprotected 5-6- and 6-6
      isomers, which gave colloidal suspensions in aqueous mixtures, displayed marked
      activity in blocking lectin-induced hemagglutination by concanavalin A.

PMID- 17191790
TI  - Efforts towards the design of 'teflon' proteins: in vivo translation with
      trifluorinated leucine and methionine analogues.
AB  - In vivo incorporation of monofluorinated noncanonical amino acids into
      recombinant proteins has been well-established for decades. Proteins fluorinated
      in this way proved to be useful tools for many practical applications. In
      contrast, trifluorinated amino acids have been incorporated in only a few
      peptides and relatively small proteins by using expression systems in living
      cells. A novel class of proteins with a fluorous core can be envisaged only if
      full replacement of the core-building hydrophobic and aliphatic amino acids such
      as leucine or methionine with the related analogues trifluoromethionine and
      trifluoroleucine would be feasible. However, our systematic efforts to introduce
      these amino acids in larger proteins (over 10 Da) that contain different
      structural motifs clearly show that only partial substitutions are possible. The
      reasons are high toxicity of these substances and difficulties to accommodate
      them into the compact cores of natural proteins without adverse effects on their
      structural integrity. Therefore, engineering of such three dimensional 'Teflon'
      like structures would require, besides an expansion of the amino acid repertoire
      of the genetic code, a de novo protein design as well.

PMID- 17191791
TI  - Biochemical association of poly(ADP-ribose) polymerase-1 and its apoptotic
      peptide fragments with DNA polymerase beta.
AB  - We have characterized the biochemical association of two DNA damage-dependent
      enzymes, poly(ADP-ribose) polymerase-1 (PARP-1) [EC 2.4.2.30] and DNA polymerase
      beta (pol beta) [2.7.7.7]. We reproducibly observed that pol beta is an efficient
      covalent target for ADP-ribose polymers under standard conditions of
      enzymatically catalyzed ADP-ribosylation of betaNAD+ as a substrate. The
      efficiency of poly(ADP-ribosyl)ation increased as a function of the pol beta and
      betaNAD+ concentrations. To further characterize the molecular interactions
      between these two unique polymerases, we also subjected human recombinant PARP-1
      to peptide-specific enzymatic degradation with either caspase-3 or caspase-7 in
      vitro. This proteolytic treatment, commonly referred to as 'a hallmark of
      apoptosis', generated the two physiologically relevant peptide fragments of PARP
      1, e.g., a 24-kDa amino-terminus and an 89-kDa carboxy-terminal domain.
      Interestingly, co-incubation of the two peptide fragments of PARP-1 with full
      length pol beta resulted in their domain-specific molecular association as
      determined by co-immunoprecipitation and reciprocal immunoblotting. Therefore,
      our data strongly suggest that, once PARP-1 is proteolyzed by either caspase-3 or
      caspase-7 during cell death, the specific association of its apoptotic fragments
      with DNA repair enzymes, such as pol beta, may serve a regulatory molecular role
      in the execution phase of apoptosis.

PMID- 17191792
TI  - New photoproducts from irradiation of NADH with near-UV light.
AB  - Adenosine 5'-diphosphoribose (ADPR) and a second compound, which may be
      nicotinamide, are the newly discovered photoproducts resulting from irradiation
      of beta-nicotinamide adenine dinucleotide (beta-NADH) in the wavelength range of
      300-400 nm under oxygen-poor conditions. Both products emerge there even
      exclusively, whereas, at higher oxygen concentrations, the oxidized form of
      nicotinamide adenine dinucleotide (NAD+) is additionally formed, although still
      as a minor product. The development of ADPR and NAD+ is clearly oxygen-dependent,
      while, for the formation of the second photoproduct, small quantities of oxygen
      appear to be sufficient.

PMID- 17191793
TI  - Adamantylsulfanyl- and N-adamantylcarboxamido-derivatives of heterocycles and
      phenols: synthesis, crystal structure, tumor necrosis factor-alpha production
      enhancing properties, and theoretical considerations.
AB  - The synthesis of several adamantylthio heterocycles and S-adamantylated
      thiocresols is reported. The attack of the adamantyl cation formed from 1
      adamantan-1-ol in refluxing trifluoroacetic acid provides the corresponding
      adamantylsulfanyl compounds. The use of the adamantyl cation in the Ritter
      reaction gave the number of N-adamantylcarboxamide derivatives of heterocyclic
      and phenolic compounds. Adamantylsulfanyl heterocycles, contrary to N
      adamantylcarboxamido compounds, enhanced the production of tumor necrosis factor
      alpha (TNF-alpha) in genetically modified murine melanoma cells transduced with
      the gene for human TNF-alpha. The highest activity, comparable to that of the
      most-active previously described for 6-methyl-2-[(adamantyl)amino]pyridine,
      showed 2-thioadamantyl derivatives of pyridine and 6-methylpyridine. The crystal
      structures of carboxamido and sulfanyl analogues of 2-(1-adamantylamino)pyridine
      have been studied, and consecutive quantum-chemical calculations have been
      performed. The low TNF-alpha production stimulatory activity of N
      adamantylcarboxamido-pyridine compared to the sulfanyl and amino analogues is
      postulated to be linked to the conformational rigidity of the former one enhanced
      by the formation of the intramolecular H-bond. The comparison of the activity of
      2-(1-adamantylsulfanyl)-6-methylpyridine and (1-adamantylsulfanyl)-2
      methylbenzene proved the importance of the ring N-atom, whereas the differences
      in activity between bromo and methyl analogues pointed at electronic rather than
      steric influence of ortho-substituents on the biological activity.

PMID- 17191794
TI  - Oldhamiphylline A: a novel hexacyclic alkaloid from Daphniphyllum oldhami.
AB  - A novel Daphniphyllum alkaloid, oldhamiphylline A (1), together with five known
      alkaloids, deoxycalyciphylline B, deoxyisocalyciphylline B, calyciphylline,
      secodaphniphylline, and calycicine A, was isolated from the leaves of
      Daphniphyllum oldhami. The structure of 1 was established by spectroscopic
      methods, especially 2D NMR techniques (1H,1H-COSY, HMQC, HMBC, and NOESY).

PMID- 17191795
TI  - A new type of floral oil from Malpighia coccigera (Malpighiaceae) and chemical
      considerations on the evolution of oil flowers.
AB  - New, partially acetylated dihydroxy fatty acids could be identified in the floral
      oil of Malpighia coccigera (Malpighiaceae): 7-OAc,3-OH 20:0, 7-OAc,3-OH 22:0, 9
      OAc,3-OH 22:0, 9-OAc,5-OH 22:0, 3,9-diOAc 22:0, 9-OAc,3-OH 24:0, and 11-OAc,5-OH
      24:0. The substitution patterns of all hitherto undescribed dihydroxylated and
      additionally identified monohydroxylated fatty acids are in agreement with a
      polyketide analogous biosynthesis. Intermediates may be 3-acetoxy fatty acids
      (C16, C18, and C20), known from flower secretions of other phylogenetically
      unrelated plant families. A possible relationship between plant epicuticular wax
      and floral oil biosynthesis is discussed. It may explain why an independent but
      convergent development of oil flowers and flower oils in unrelated plant families
      was possible.

PMID- 17191796
TI  - Synthesis and in vitro antineoplastic evaluation of certain 16-(4-substituted
      benzylidene) derivatives of androst-5-ene.
AB  - In a systematic effort aimed at identifying new steroidal cytotoxic agents with
      potent antiproliferative activity against cancer cells, we synthesized certain 16
      [4-(NO2, CN, and i-Pr)substituted]benzylidene derivatives of androst-5-ene, 7-25,
      with pyrrolidino functionality in the 3beta-position of the steroid nucleus,
      i.e., 13-18 and 25. The selected compounds were examined for their cytotoxicity
      against a panel of three human cancer cell lines at the National Cancer Institute
      (NCI), Bethesda, USA. The results presented herein provide experimental evidence
      that compounds 7, 9, 10, 12, 16, and 19-21 induced apoptosis in human cancer
      cells.

PMID- 17191797
TI  - Synthesis of (2'S)- and (2'R)-2'-deoxy-2'-[(2-methoxyethoxy)amino] pyrimidine
      nucleosides and oligonucleotides.
AB  - Syntheses of specified 2'-modified nucleosides were achieved: a) via oximation of
      the 5',3'-blocked 2'-oxocytidine, followed by reduction, or b) by intramolecular
      nucleophilic addition of 3'-(2-methoxyethoxy)carbamate to the 2'-position with
      opening of O(2),2'-anhydrouridine. For the first time, 3'-phosphoroamidites of
      these 2'-modified nucleosides were successfully incorporated into
      oligonucleotides by solid-phase synthesis. Incorporation of 2'-modified
      nucleotides into oligodeoxyribonucleotides had a negative effect on the duplex
      T(m) values with the DNA or RNA complements. Nevertheless, modified nucleotides
      have shown good target recognition; the (S)-isomer binds preferably to RNA and
      the (R)-isomer to DNA. Both modified nucleosides significantly increased nuclease
      resistance of the oligodeoxyribonucleotides.

PMID- 17191799
TI  - Calculation of the specific rate of catabolic activity (Ac) from the heat flow
      rate of soil microbial reactions measured by calorimetry: significance and
      applications.
AB  - The calculation of parameters involved in the kinetics of the microbial soil
      reactions linked to the carbon cycle is strongly limited by the methodologies
      employed. Hence, a mathematical model is proposed to quantify easily the specific
      rate of catabolic activity A(c) by microcalorimetry based on Belaich's model. It
      permits to quantify A(c) from the plots of the heat flow rate vs. time recorded
      from soil samples amended with glucose. It was applied for several soil samples
      collected in the Amazon. The results obtained were compared, and statistical and
      graphical analyses were used to provide the biophysical significance of A(c) in
      soils. Results suggest that A(c) could be used as an empirical measure of stress.
      It correlates positively with the heat yield, Y(Q/X), of the soil microbial
      growth reactions, indicating that higher specific rates of catabolic activity
      cause higher dissipation of energy per unit of cell, yielding less-efficient
      metabolic reactions, which could affect negatively the soil quality. It is
      strongly affected by the initial microbial population and by the percentage of
      nitrogen in the samples. The statistical analysis also demonstrated that A(c) is
      more sensitive to changing environmental conditions than Y(Q/X), yielding more
      accurate information about the soil metabolic processes.

PMID- 17191798
TI  - Isomeric eremophilane lactones from Senecio tsoongianus.
AB  - From the whole plant of Senecio tsoongianus, two pairs of epimers,
      tsoongianolides A (1) and B (2), and tsoongianolides C (3) and D (4), and two new
      sesquiterpene lactones, tsoongianolides E (5) and F (6), all of which possess the
      eremophilane skeleton, were isolated. Two known eremophilane dimers (7) and (8)
      were also obtained from this species. Their absolute structures were elucidated
      by 1D- and 2D-NMR techniques and by X-ray diffraction studies, along with
      chemical evidence.

PMID- 17191800
TI  - Post-impact assessment of oil pollution in Agbada west plain of Niger Delta,
      Nigeria: field reconnaissance and total extractable hydrocarbon content.
AB  - Typical post-impact assessment of an oil-spill-impacted site in Agbada west plain
      of the Niger Delta basin of Nigeria was carried out 13 months after recorded
      incidence of spillage, using empirical indices of reconnaissance and extractable
      hydrocarbon content. Field-reconnaissance surveys revealed lower species' numbers
      and diversity of surface and subterranean flora and fauna. The presence and
      absence of such plant species as Elaeis guineensis, Musanga cecropiodes, and
      Andropogon gayanus, as well as animal species like earthworms and nematodes in
      sampled plots, corroborated the evidence provided by the total extractable
      hydrocarbon content (of (2.53+/-0.43)x10(2) mg/kg and (2.00+/-0.76)x10(2) mg/kg
      at surface and subsurface depths, resp.) on the level of degradation and/or
      regeneration at the polluted site. The most important evidence that oiling must
      have been responsible, at least in part, for the reduction in species' number and
      diversity was provided by the plant cover, Andropogan gayanus, which occurred at
      a lower density of 0.9 plants/m2 in the oil-impacted plots and 14.00 plants/m2 in
      the unimpacted reference plots of an adjacent, geographically similar area. The
      presence of this species on site thus presented a significant difference (P<0.05)
      of over 85%, and indicated exhaustion or impoverishment of impacted soils. Elaeis
      guineensis, with a population density of 0.1 stands/m2, provided evidence of past
      cultivation on site, while species like Musanga cecropioides, with a density of
      0.5 stands/m2, at the unimpacted site, confirmed the abandonment of the farmstead
      over a long period of time. For the fauna, the most sensitive indicator of
      hydrocarbon toxicity was provided by nematode Xiphinema sp. that were completely
      absent in the oil-impacted site.

PMID- 17191801
TI  - Chenoalbicin, a novel cinnamic acid amide alkaloid from Chenopodium album.
AB  - The roots of Chenopodium album were infused in MeOH, and the extract was
      partitioned between AcOEt and H2O. AcOEt-Soluble material was subjected to
      different silica-gel column chromatographies and then purified by reverse-phase
      HPLC to afford a new cinnamic acid amide alkaloid as a racemic mixture. The new
      compound, named chenoalbicin (1), was characterized by extensive spectroscopic
      investigation, especially 1D and 2D NMR spectroscopy. Its effects on the
      germination and growth of Lactuca sativa L. has been studied. The results are
      reported as percentage differences of germination, root elongation, and shoot
      elongation from the control at concentrations ranging from 10(-4) to 10(-7) M.

PMID- 17191802
TI  - Chemistry and biodiversity.
AB  - Complex structures produced by noncatalyzed multi-step chemical processes must
      have highly probable origins and assembly routes. Within any frame of reference,
      life is easily the most-complex self-assembled structure known to man. It is not
      possible to calculate a finite time for biogenesis by statistical mechanics, but
      the abundance of life makes it reasonable to propose an accelerating principle of
      nature that naturally shortened the time for cell formation to a billion years or
      less. This hypothetical principle, which I have called valence-orbital bias, is
      thought to be responsible for the discrepancy between statistics and observation,
      and carries with it, as a conditio sine qua non, multiple origins of life.The new
      concept resolves the differences between the predictions based on statistical
      mechanics and the relatively rapid appearance of life during the post-accretion
      period. It suggests as well that species and variants, the units of propagation,
      may also have been the units of evolution. Produced in profusion by chemistry,
      the origins are culled by natural selection, whereby failure means extinction,
      not adaptation. Biodiversity, thus, becomes a direct consequence of chemistry
      without positive feedback from the environment and without a constructive role
      for mutation.

PMID- 17191803
TI  - Chemistry and biodiversity: Darwinism, evolution, and speciation. An opposing
      view.

PMID- 17191804
TI  - Non-xanthine antagonists for the adenosine A1 receptor.

PMID- 17191805
TI  - Swertia (Gentianaceae): chemical and pharmacological aspects.
AB  - A compilation of the constituents isolated from Swertia species covering the
      literature up to December 2003 is presented. The botanical classification and
      ethno-pharmacology of Swertia plants, as well as the biological activities and
      pharmacological applications of both distinct phytochemicals and medicinally
      active plant materials (formulations, extracts, etc.) are discussed in detail.

PMID- 17191806
TI  - The pheromone production of female Plodia interpunctella is inhibited by
      tyraminergic antagonists.
AB  - Several compounds were found to suppress the calling behavior and in vitro
      pheromone biosynthesis of the Indian meal moth, Plodia interpunctella. The
      compounds were screened by means of a calling-behavior bioassay with female P.
      interpunctella. Five derivatives with activities in the nanomolar range were
      identified, in order of decreasing pheromonostatic activity: 4
      hydroxybenzaldehyde semicarbazone (42) > 5-(4-methoxyphenyl)-1,3-oxazole (38) > 5
      [4-(tert-butyl)phenyl]-1,3-oxazole (40) > 5-(3-methoxyphenyl)-1,3-oxazole (35) >
      5-(4-cyanophenyl)-1,3-oxazole (36). These compounds also showed in vitro
      inhibitory activity in intracellular de novo pheromone biosynthesis, as
      determined with isolated pheromone-gland preparations that incorporated [1
      (14)C]sodium acetate in the presence of the so-called pheromone-biosynthesis
      activating neuropeptide (PBAN). The non-additive effect of the inhibitor with
      antagonist (yohimbine) for the tyramine (TA) receptor suggests that it could be a
      tyraminergic antagonist. Three-dimensional (3D) computer models were built from a
      set of compounds. Among the common-featured models generated by the program
      Catalyst/HipHop, aromatic-ring (AR) and H-bond-acceptor-lipophilic (HBAl)
      features were considered to be essential for inhibitory activity in the calling
      behavior and in vitro pheromone biosynthesis. Active compounds, including
      yohimbine, mapped well onto all the AR and HBAl features of the hypothesis. Less
      active compounds were shown to be unable to achieve an energetically favorable
      conformation, consistent with our 3D common-feature pharmacophore models. The
      present hypothesis demonstrates that calling behavior and PBAN-stimulated
      incorporation of radioactivity are inhibited by tyraminergic antagonists.

PMID- 17191807
TI  - Structure elucidation and antioxidant activity of (-)-isosilandrin isolated from
      Silybum marianum L.
AB  - A regioisomer of the known flavanolignan (-)-silandrin (3a), named (-)
      isosilandrin (8a), was isolated from the fruits of a white-flowered variant of
      Silybum marianum L. populated in Hungary. Its structure was established both by
      spectroscopic methods and total synthesis, and its absolute configuration was
      determined by means of circular dichroism. This compound showed stronger
      inhibitory activity on the superoxide anion (O2*-) release by human
      polymorphonuclear leukocytes (PMNL) than (+)-silybin (1a,b).

PMID- 17191808
TI  - Exploratory studies to investigate a linked prebiotic origin of RNA and coded
      peptides. 3rd communication. Behaviour of 5-amino-1H-imidazole-4-carbonitrile
      derivatives.
AB  - The potentially prebiotic synthesis of pyrimidine ribonucleotides by stepwise
      nucleobase assembly on arabinose-3-phosphate derivatives has been demonstrated in
      previous work. The generation of xylose-2-phosphate derivatives by aldolisation,
      and the behaviour of these compounds under the conditions of pyrimidine
      nucleobase assembly have also been described. In this paper, the scope for
      generation of purine nucleotides via 3,3'-anhydro-xylo-nucleotides is
      investigated. In neutral D2O solution, the potential intermediate 47 (Schemes 6
      and 8) undergoes H-C2 --> D-C2 exchange, but no appreciable reaction with cyanide
      or cyanamide occurs. The exchange chemistry expands options for purine nucleobase
      assembly on sugar phosphate scaffolds.

PMID- 17191809
TI  - Novel biologically active bibenzyls from Bauhinia saccocalyx Pierre.
AB  - Four new bibenzyls, bauhinols A-D (1-4), together with the two known bibenzyls 5
      and 6, were isolated from the roots of Bauhinia saccocalyx, and their structures
      were elucidated by analyses of spectroscopic data. Bauhinol A (1) exhibits
      significant cytotoxicity towards NCI-H187 (small-cell lung cancer), BC (breast
      cancer), and KB (oral-cavity cancer) cell lines, with IC50 values of 2.7-4.5
      microg/ml. Bauhinol B (2) is cytotoxic against NCI-H187 (IC50 = 1.1 microg/ml)
      and BC (IC50 = 9.7 microg/ml) cell lines, but inactive toward the KB cell line
      (at 20 microg/ml). Compound 2 also is mildly antifungal towards Candia albicans
      (IC50 = 28.9 microg/ml). Bibenzyl 6 is active against NCI-H187 (IC50 = 14.1
      microg/ml) and BC (IC50 = 4.0 microg/ml) cells, but inactive (at 20 microg/ml)
      toward the KB cell line. Compounds 1, 2, and 6 show mild antimycobacterial
      activities, with MIC values of 25-50 microg/ml, but are inactive at 20 microg/ml
      against the K1 malarial parasite strain (Plasmodium falciparum). While bauhinol A
      (1) is inactive against cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2),
      compounds 2 and 6 inhibit both COX-1 and COX-2, with IC50 values comparable to
      those of the standard drug, aspirin (Table 3).

PMID- 17191810
TI  - Novel antibacterial diterpenoids from Larix chinensis Beissn.
AB  - Two novel labdane-type diterpenoids, butanedioic acid mono[(13S)-13-hydroxylabda
      8(17),14-dien-19-yl] ester (1) and butanedioic acid bis[(13S)-13-hydroxylabda
      8(17),14-dien-19-yl] ester (2), along with the eleven known diterpenoids 3-13 and
      three other known compounds, were isolated from the bark of Larix chinensis.
      Their structures were elucidated both spectroscopically and chemically. The major
      diterpenoids 1-9, 11, and 13, as well as the very abundant phenolic compound 16,
      were subjected to antibacterial and cytotoxic bioassays. Compounds 7 and 9 showed
      remarkable in vitro inhibition of Staphylococcus aureus and S. epidermidis (MIC =
      37-73 microM).

PMID- 17191811
TI  - Trace heavy metals associated with crude oil: a case study of Ebocha-8 oil-spill
      polluted site in Niger Delta, Nigeria.
AB  - The Ebocha-8 oil-spill-polluted site was identified as study site according to
      field reconnaissance surveys of oil-polluted sites in Obiobi/Obrikom prospect
      area of Niger Delta. A sampling area was delimited at each of the oil-spill
      affected sites by the grid technique, and soils were collected at surface (0-15
      cm) and subsurface (15-30 cm) depths from three replicate quadrants. A
      geographically similar, unaffected area, located in 50-m distance from each
      contaminated site, was chosen as control site. Trace heavy metals, Ni, V, Cu, Cd,
      and Pb, which are normal constituents of crude oil, were determined in the soils
      by atomic-absorption spectrophotometry after pre-extraction of cations with
      dithionite-citrate carbonate. Ni varied from 0.53 to 18.00 mg/kg, Cu from 0.15 to
      0.30 mg/kg, and Pb from 0.32 to 0.80 mg/kg in surface and subsurface soils,
      respectively; Cd and V were less than 0.20 mg/kg in all sampled plots. Ni, Cu,
      and Pb were more enhanced (P<0.05) in the oil-spill-polluted soils, especially at
      surface depth, and this may be attributed to the fact that metal profiles in
      polluted soils penetrate a little below the 10-cm region, even after many years,
      thereby making the metal concentration in surface soils usually higher. Whilst
      the Ebocha-8 oil spillage may be responsible, at least in part, for the enhanced
      concentrations and paucity of variations in the metal concentrations of sampled
      plots, other factors such as the physicochemical characteristics of soils (e.g.,
      soil pH and organic-matter content) and relative mobility of these metals, as
      well as the intense rainfall and flooding that preceded the period of sampling,
      may also have contributed in part. Enhanced levels of these micronutrients in the
      soils may result in enhanced absorption by plants, which may bring about possible
      bioaccumulation by such plants and the animals that depend on them for survival,
      and all of these may lead to toxic reactions along the food chain.

PMID- 17191813
TI  - Solution-phase synthesis of Aib-containing cyclic hexapeptides.
AB  - The 18-membered Aib-containing cyclohexapeptides, cyclo(-Gly-Aib-Aib-Gly-Aib-Phe
      ) (22), cyclo(-Gly-Aib-Phe(2Me)-Gly-Aib-Aib-) (24a), cyclo(-Gly-Phe(2Me)-Aib-Gly
      Aib-Aib-) (24b), and cyclo(-Gly-Phe(2Me)-Aib-Gly-Aib-Phe-) (25), have efficiently
      been synthesized by solution-phase techniques. The linear precursors 1a-1d were
      prepared by combining the 'azirine/oxazolone method' for incorporation of
      alpha,alpha-disubstituted alpha-amino acids (Aib, Phe(2Me)) into the peptide
      chains by classical peptide coupling methods for segment condensations.
      Deprotection of the amino and carboxy termini of 1a-1d, followed by cyclization
      with DEPC as the coupling reagent, gave the above-mentioned cyclic hexapeptides
      22, 24a, 24b, and 25 in good yields (26-57%). The solid-state conformations of
      the linear hexapeptides 1d, 16 and 27, and of the cyclohexapeptides 22 and 25
      have been established by X-ray crystallography.

PMID- 17191812
TI  - Antioxidant/prooxidant effects of dietary non-flavonoid phenols on the Cu2+
      induced oxidation of human low-density lipoprotein (LDL).
AB  - A central role in the oxidative development of atherosclerotic lesions has been
      ascribed to the peroxidation of plasma low-density lipoprotein (LDL). Dietary
      supplementation with virgin olive oils increases the total plasma antioxidant
      status and the resistance of low-density lipoprotein to ex vivo oxidation. We
      have studied the effects of some dietary non-flavonoid phenols from Olea europaea
      L., both in purified form or in complex mixtures obtained by biotransformation of
      olive leaf extracts, on the LDL oxidation induced by Cu2+ ions. Cu2+-Induced LDL
      oxidation is inhibited by oleuropein and hydroxytyrosol in the initiation phase
      of the reaction at concentrations of phenols higher than that of Cu2+ ions.
      Interestingly, at lower concentration, both phenols anticipated the initiation
      process of LDL oxidation, thus exerting prooxidant capacities. Although similar
      effects are already described for flavonoids, such as quercetin, rutin, and
      apigenin, it is the first time that a prooxidant effect of dietary non-flavonoid
      phenols, such as oleuropein and hydroxytyrosol, on the LDL oxidation is reported.
      Our results show that a net effect of oleuropein and hydroxytyrosol on Cu2+
      induced LDL peroxidation is determined by a balance of their pro- and antioxidant
      capacities. It is worth to underline that, during Cu2+-induced LDL oxidation in
      the presence of bioreactor eluates, we have evidence of a synergistic effect
      among phenolic compounds that enhance their antioxidant capacities so avoiding
      the prooxidant effects.

PMID- 17191815
TI  - Total synthesis and biological evaluation of a C(10)/C(12)-phenylene-bridged
      analog of epothilone D.
AB  - The total synthesis of compound 8, a conformationally constrained analog of
      epothilone D (2), has been achieved through a convergent strategy based on three
      key fragments comprising C(1)-C(6) (26), C(7)-C(12) (16), and C(13)-O(16) (19) of
      the macrocyclic framework. Construction of the C(12)-C(13) bond involved Pd(0)
      mediated B-alkyl Suzuki coupling between aryl bromide 16 and olefin 19, and
      proceeded in excellent yield, while formation of the C(6)-C(7) bond through aldol
      reaction was somewhat less efficient. Surprisingly, macrolactonization was rather
      low-yielding and gave protected 8 only in 39% yield. Although 8 had been
      suggested by pharmacophore modeling to adopt a conformation similar to the
      bioactive conformation of epothilone B, the compound was devoid of any
      significant antiproliferative activity.

PMID- 17191814
TI  - Identification of delphinidin 3-O-(6''-O-malonyl)-beta-glucoside-3'-O-beta
      glucoside, a postulated intermediate in the biosynthesis of ternatin C5 in the
      blue petals of Clitoria ternatea (butterfly pea).
AB  - Ternatins are blue anthocyanins found in the petals of Clitoria ternata
      (butterfly pea). Among them, ternatin C5 (delphinidin 3-O-(6''-O-malonyl)-beta
      glucoside-3',5'-di-O-beta-glucoside; 2) has the structure common to all the
      ternatins, which is characterized by its glucosylation pattern: a 3,3',5'
      triglucosylated anthocyanidin. In the course of studying biosynthetic pathways of
      ternatins, the key enzymatic activities to produce ternatin C5 were discovered in
      a crude enzyme preparation from the petals of a blue petal line of C. ternatea.
      When this preparation was tested for activity against several delphinidin
      glycosides, delphinidin 3-O-(6''-O-malonyl)-beta-glucoside-3'-O-beta-glucoside
      (6), a postulated intermediate, was found in the reaction mixture, together with
      three known anthocyanins, which were spectroscopically structurally identified.
      As a result of structural identification, the following enzymatic activities were
      identified: UDP-glucose :delphinidin 3-O-(6''-O-malonyl)-beta-glucoside-3'-O-beta
      glucoside 5'-O-glucosyltransferase (5'GT), UDP-glucose :delphinidin 3-O-(6''-O
      malonyl)-beta-glucoside 3'-O-glucosyltransferase (3'GT), UDP-glucose :delphinidin
      3-O-glucosyltransferase, and malonyl-CoA :delphinidin 3-O-beta-glucoside 6''
      malonyltransferase. In a mauve petal line, which did not accumulate ternatins but
      delphinidin 3-O-(6''-O-malonyl)-beta-glucoside in its petal, there were neither
      5'GT nor 3'GT activities. Thus, the early biosynthetic pathway of ternatins may
      be characterized by the stepwise transfer of two glucose residues to 3'- and 5'
      position of delphinidin 3-O-(6''-O-malonyl)-beta-glucoside (1; Scheme) from UDP
      glucose.

PMID- 17191816
TI  - Synthesis of 7-oxasphingosine and -ceramide analogues and their evaluation in a
      model for apoptosis.
AB  - The 7-oxasphingosine (1), 7-oxaceramide (2), the thio-oxaceramide 3, and N
      methyloxaceramide 4 were synthesised from D-galactose via the building block 9.
      The apoptosis-inducing properties of 1-4 were compared to those of sphingosine
      (Sph) and ceramide (Cer) using a human neuroblastoma (SK-N-BE) and a murine
      promyelocyte-derived (32d) cell line. There were no differences between 2-4 and
      Cer in terms of their effects on the viability of cells and their ability to
      trigger cell proliferation. However, in the presence of N,N-dimethylsphingosine,
      an inhibitor of sphingosine kinase (SPHK), Cer was more potent than thio-ceramide
      3 in 32d cells, while thio-ceramide 3 was more potent and efficacious in SK-N-BE
      cells, where it showed an IC50 value of 3 nM compared to 100 nM for Cer. In both
      SK-N-BE and 32d cells, 7-oxasphingosine (1) and Sph were equally toxic, even in
      the presence of N,N-dimethylsphingosine.

PMID- 17191817
TI  - Photooxidation of pterin in aqueous solutions: biological and biomedical
      implications.
AB  - Studies of the photochemical reactivity of pterin (= 2-aminopteridin-4(3H)-one;
      PT) in acidic (pH 5.0-6.0) and alkaline (pH 10.2-10.8) aqueous solutions have
      been performed. The photochemical reactions were followed by UV/VIS
      spectrophotometry, thin layer chromatography (TLC), high-performance liquid
      chromatography (HPLC), and an enzymatic method for H2O2 determination. PT is not
      light-sensitive in the absence of molecular oxygen, but it undergoes
      photooxidation in the presence of O2, yielding several nonpteridinic products.
      The quantum yields for PT disappearance were found to be 8.2 (+/-0.6) x 10(-4)
      and 1.2 (+/-0.2) x 10(-3) in acidic and alkaline media, respectively. H2O2 was
      detected and quantified in irradiated solutions of PT; and its importance from a
      biomedical point of view is discussed. The rate constant of the chemical reaction
      between singlet oxygen ((1)O2) and PT was determined to be 2.5 (+/-0.2) x 10(5) l
      mol(-1) s(-1) in alkaline medium, and the role of (1)O2 in the photooxidation of
      pterin was evaluated.

PMID- 17191818
TI  - Pharmacokinetic investigation of a 14C-labelled beta 3/alpha tetrapeptide in
      rats.
AB  - The solid-phase synthesis and an ADME investigation with albino and pigmented
      male rats of the doubly 14C-labelled beta/alpha-tetrapeptide derivative Ac-beta3
      hTyr-(D)Trp-beta3 hLys-beta3 hThr-lactone (3; Fig. 3) are described. After
      intravenous (i.v.) and peroral (p.o.) administration of the peptide, its
      concentration in blood and plasma, its tissue distribution, and the metabolism
      and the excretion of the peptide were analyzed over a period of up to 7 days post
      dose. The tetrapeptide in its ring opened form, 5, has a bioavailability of ca.
      25%; radioactivity is distributed in the animals in an organ-specific way, and
      the compound appears to pass the blood-brain barrier to a very small extent, if
      at all (Tables 1-3 and Figs. 2-6). Excretion (37% renal, 44% fecal, including
      biliary) of the tetrapeptide 4 days after i.v. administration is almost complete,
      with only 4.3% remaining in the carcass; 4 days after p.o. administration 97% of
      the dose has been excreted in the feces. Radiochromatograms taken of plasma (0.5
      and 24 h after i.v. dosing) and of urine and feces extracts (0-48 h collected)
      reveal the presence of lactone 3 and/or the corresponding hydroxy acid 5 with
      essentially no or very minor other peaks, respectively, representing possible
      metabolites (Tables 4-6, and Fig. 7 and 8). A comparison with a previous ADME
      investigation of a beta-nonapeptide show that--except for the lack of metabolism-
      all aspects of exposure, distribution, and elimination are different (structure
      specific properties). The investigated tetrapeptide 3 is a potent and highly
      specific agonist of the somatostatin receptor hsst4, rendering the results
      described herein promising for diagnostic and therapeutic applications of beta
      peptides.

PMID- 17191819
TI  - Prediction of aqueous solubility based on large datasets using several QSPR
      models utilizing topological structure representation.
AB  - Several QSPR models were developed for predicting intrinsic aqueous solubility,
      S(o). A data set of 5,964 neutral compounds was sub-divided into two classes,
      aromatic and non-aromatic compounds. Three models were created with different
      methods on both data sets: two regression models (multiple linear regression and
      partial least squares) and an artificial neural network model. These models were
      based on 3343 aromatic and 1674 non-aromatic compounds for training sets; 938
      compounds were used in external validation testing. The range in -log S(o) is 
      1.6 to 10. Topological structure descriptors were used with all models. A genetic
      algorithm was used for descriptor selection for regression models. For the
      artificial neural network (ANN) model, descriptor selection was done with a
      backward elimination process. All models performed well with r2 values ranging
      0.72 to 0.84 in external validation testing. The mean absolute errors in
      validation ranged from 0.44 to 0.80 for the classes of compounds for all the
      models. These statistical results indicate a sound ANN model. Furthermore, in a
      comparison with eight other available models, based on predictions using a
      validation test set (442 compounds), the artificial neural network model
      presented in this work (CSLogWS) was clearly superior based on both the mean
      absolute error and the percentage of residuals less than one log unit. In the ANN
      model both E-State and hydrogen E-State descriptors were found to be important.

PMID- 17191820
TI  - Bioactive terpenoids and guggulusteroids from Commiphora mukul gum resin of
      potential anti-inflammatory interest.
AB  - Guggulu, the gum resin from Commiphora mukul, is one of the components of various
      formulations of traditional Ayurvedic medicine to treat inflammation, obesity,
      and lipid disorders. In most preparations of Ayurvedic medicine in India, guggulu
      is boiled prior to its use. Therefore, guggulu was boiled with H2O prior to
      extractions in our study. Bioassay-guided isolation of compounds from the hexane
      soluble portion of the MeOH extract of guggulu yielded cembrenoids, 1-6, a
      bicyclic diterpene, 7, guggulusterone derivatives, 8-11, myrrhanone derivatives,
      12, myrrhanol derivative, 13, and a lignan, 14. The structures of these compounds
      were confirmed by spectroscopic methods. Compounds 5, 6, 7, 10, and 12-14 are
      novel. These compounds were assayed for lipid peroxidation and cyclooxygenase
      (COX) enzyme inhibitory activities. At 100 ppm, compounds 3, 6, and 14 inhibited
      the lipid peroxidation by 79, 57, and 58%, respectively, and the rest of isolated
      compounds showed 20-40% inhibitory activity with respect to the controls. In COX
      1 and COX-2 enzyme inhibitory assays, compound 3 showed 79 and 83%, and compound
      8 gave 67 and 54% of inhibition, respectively, at 100 ppm. All fourteen compounds
      inhibited COX-1 enzyme at 100 ppm. The lipid peroxidation and COX enzyme
      inhibitory activities exhibited by compounds isolated from C. mukul may
      substantiate its use in traditional medicine.

PMID- 17191824
TI  - Molecular and cellular basis of human olfaction.
AB  - The human olfactory systems recognize and discriminate a large number of
      different odorant molecules. The detection of chemically distinct odorants begins
      with the binding of an odorant ligand to a specific receptor protein in the
      ciliary membrane of olfactory neurons. To address the problem of olfactory
      perception at a molecular level, we have cloned, functionally expressed, and
      characterized some of the human olfactory receptors from chromosome 17. Our
      results show that a receptor protein is capable of recognizing the particular
      chemical substructure of an odor molecule and, therefore, is able to respond only
      to odorants that have a defined molecular structure. These findings represent the
      beginning of the molecular understanding of odorant recognition in humans. In the
      future, this knowledge could be used for the design of synthetic ideal receptors
      for specific odors (biosensors), or the perfect odor molecule for a given
      receptor.

PMID- 17191825
TI  - From the linden flower to linden honey--volatile constituents of linden nectar,
      the extract of bee-stomach and ripe honey.
AB  - Honey is produced by honeybees (Apis mellifera), which collect nectar from
      flowers, digest it in their bodies, and deposit it in honeycombs, where it
      develops into ripe honey. We studied the evolution of the volatile constituents
      from the nectar of linden blossoms (Tilia cordata) to honey via the
      'intermediate' honeybee. The sampling of the contents of the honey stomach or
      honey sack of the bee is unique. Extracts were prepared from nectar, from the
      liquid of the honey stomach, and from ripe honey. The chemistry is extremely
      complex, and compounds spanning from monoterpenes (hydrocarbons, ethers,
      aldehydes, acids, and bifunctional derivatives), isoprenoids, aromatic compounds
      (phenylpropanoids, phenols), and products degraded from fatty acids to alkaloids,
      were identified. Some compounds definitely stem from the plants, whereas other
      interesting constituents can be attributed to animal origin. Two derivatives of
      decanoic acid, 9-oxodec-2-enoic acid (12) and 9-hydroxydec-2-enoic acid,
      identified in the honey are known to be constituents of the so-called 'Queen's
      pheromone'. Two metabolites of these acids were identified in the extract of the
      honey stomach: 8-oxononanal (10), a new natural product, and 8-oxononanol (11).
      There structures were confirmed by synthesis. Nectar and honey stomach contain
      many aldehydes, which, due to the highly oxidative atmosphere in the honeycomb,
      are found as corresponding acids in the honey. Two acids were newly identified as
      4-isopropenylcyclohexa-1,3-diene-1-carboxylic acid (14) and 4-(1-hydroxy-1
      methylethyl)-cyclohexa-1,3-diene-1-carboxylic acid (15).

PMID- 17191826
TI  - 14-Methylpentadecano-15-lactone (muscolide): a new macrocyclic lactone from the
      oil of Angelica archangelica L.
AB  - The chemical composition of seed and root oils from Angelica archangelica L. was
      investigated. Analyses were performed by GC/MS and GC using two columns of
      different polarities (polyethylene glycol (DB-Wax) and 5% phenyl/95%
      polydimethylsiloxane (HP-5)), for the separation of several co-eluting
      components. A total of 58 compounds were identified, accounting for 96.3% (seed)
      and 93.5% (root) of the oils, respectively. A high content of beta-phellandrene
      (74.7%) was found in Angelica seed oil. Root oil contained a larger amount of
      macrocyclic lactones (1.3%) in comparison to the seed oil (0.4%). Different
      harvest dates produced only slight changes in the root-oil composition. In root
      oil harvested in summer, the beta-phellandrene content increased by ca. 36%, but
      no significant changes in the relative compositions of other components were
      observed. Fresh root oils were collected in five fractions (constant time
      intervals) during steam distillation (see Table). The highest-boiling fraction
      contained 9.3% of macrocyclic lactones such as tridecano-13-lactone (5.0%), 12
      methyltridecano-13-lactone (0.4%), tetradecano-14-lactone (0.1%), pentadecano-15
      lactone (3.5%), 14-methylpentadecano-15-lactone (1; trace), hexadecano-16-lactone
      (trace), and heptadecano-17-lactone (0.2%). This is the first report of the
      occurrence of 14-methylpentadecano-15-lactone (muscolide; 1) in a natural
      product.

PMID- 17191827
TI  - Odor and (bio)diversity: single enantiomers of chiral fragrant substances.
AB  - Our sense of smell is enantioselective. This review reports interesting examples
      of single stereoisomers of natural and synthetic odorants, prepared via
      bioorganic routes, that support this statement. This article is the summary of a
      talk given at the Flavours & Fragrances 2004 conference in Manchester at the
      MCC/UMIST, 12-14 May, 2004.

PMID- 17191828
TI  - Scent through the looking glass.
AB  - In 1896, Tiemann first raised the question of whether or not enantiomers might
      exhibit different odors. The classic work of von Braun should have settled the
      issue in 1927 but the debate continued for decades, often rather acrimoniously.
      Various factors such as purity of samples and subjectivity of odors provided the
      confusion necessary to perpetuate disagreement. Nowadays, we have enough good
      quality data to know that sometimes, absolute configuration affects odor
      perception and sometimes it does not. We are, therefore, left with some
      interesting academic and commercial questions to be addressed.

PMID- 17191829
TI  - Silylating reagents: a powerful tool for the construction of isosteric analogs of
      highly branched odorants.
AB  - We have discovered that alpha-[dimethyl(thexyl)silyl]acetaldehyde (=
      [dimethyl(1,1,2-trimethylpropyl)silyl]acetaldehyde; 31) has a strong, woody odor.
      Structural analysis has shown resemblance to known odorants with similar
      organoleptic properties. On the basis of structure-odor relationships, new and
      more-powerful woody and ambery sila odorants were prepared. Further
      derivatization led to a set of compounds with very interesting organoleptic
      properties. Selected chiral compounds were also prepared stereoselectively. The
      influence of the absolute configuration on the olfactory properties was in
      agreement with theoretical assumptions. We also designed other groups of
      organosilicon odorants. The compounds discovered can be obtained in a few simple
      steps from commercially available reagents, and may find application in the
      fragrance and flavor industry. Their structures provide interesting data for
      further research on structure-odor relationships.

PMID- 17191830
TI  - New woody and ambery notes from cedarwood and turpentine oil.
AB  - The development of a new product in the chemical industry is still driven by
      needs like technical properties, price/performance ratio, biodegradability, or
      product safety. However, in terms of improving more and more on ecological
      criteria, summarized under such catchphrases as sustainable development or green
      chemistry, another important aspect is to use renewable resources as starting
      materials. This is not significantly new in fragrance chemistry, and there are a
      lot of raw materials in the perfume oils that are derived from molecules of
      renewable resources. Two commonly used materials are: longifolene (from
      turpentine oil) and cedrene (from cedarwood oil). These compounds are very
      suitable for the synthesis of woody and ambery notes, and even though it seemed
      that all possibilities were exhausted, it is actually still feasible to discover
      new molecules with excellent olfactory properties such as Ambrocenide (50a),
      which is available in three steps from alpha-cedrene. Some of these molecules
      will be treated in this review, both with respect to synthesis as well as
      structural and sensory aspects.

PMID- 17191831
TI  - A novel approach to prezizaane sesquiterpenes.
AB  - Prezizaane sesquiterpenes are an olfactorily interesting class of tricyclic
      natural products, which occur in some precious perfumery raw materials. These
      compounds are biosynthetically derived from farnesyl pyrophosphate via
      cyclization, but some questions regarding the stereoselectivity of this process
      have not yet been answered. We discuss a novel and concise access to the
      tricyclic framework of these sesquiterpenes, as exemplified by the synthesis of
      (+/-)-5-epi-sesquithuriferone (5-epi-4).

PMID- 17191832
TI  - 'Brain aided' musk design.
AB  - This brief review, including new experimental results, is the summary of a talk
      at the RSC/SCI conference flavours & fragrances 2004 in Manchester, United
      Kingdom, 12-14 May, 2004. Musk odorants have been a classical domain for computer
      aided structure-odor relationship (SOR) studies, but, contrary to sandalwood or
      amber odorants, they belong to structurally very different substance classes,
      e.g., macrocycles, aromatic polycycles, and nitro arenes. Most SOR computer
      models are restricted to one class, excluding structural diversity to increase
      predictability. But even within a musk family, structural similarities are often
      due to a common synthetic access, and do not reflect binding requirements for the
      musk receptor. Beyond that, the importance of structural key features can be
      missed, which is discussed on the example of the (4S)-Me group of Galaxolide. By
      synthesis and olfactory evaluation of Galaxolide-like shaped macrobicycles as
      model compounds for conformationally constrained (12R)-12-methyltridecano-13
      lactone, it was investigated how likely there is more than one musk receptor.
      Finally, the new family of so-called linear musks is discussed, especially with
      respect to the conformational importance of the gem-2',2'-dimethyl moiety in
      Helvetolide and the additional 2'-carbonyl group of Romandolide--structural
      features that strongly diminish the musk odor of macrocycles. On the example of 2
      methyl-2-[(E)-1,2,4-trimethylpent-2-enyloxy]propyl esters, the 'brain-aided'
      design and conformational analysis of musk odorants is illustrated. The overview
      concludes with the synthesis, odor evaluation, and conformational discussion of
      the new musk odorant 2-(3,3-dimethylcyclohexyl)propanoic acid
      ethoxycarbonylmethyl ester.

PMID- 17191833
TI  - New alicyclic musks: the fourth generation of musk odorants.
AB  - Musk odorants are one of the most important classes of fragrances in perfumery
      because they impart sensuality to perfume-oil compositions. Among the three well
      known classes of musks, a new and very exciting generation of musk odorants, the
      so-called alicyclic musks, was discovered recently, of which Helvetolide (2) and
      Romandolide (3) are the most popular representatives so far. To find new,
      structurally related alicyclic musks, we have synthesized a library of 114 unique
      alicyclic molecules with modified cyclohexyl moieties. The olfactory properties
      of all compounds were evaluated to identify the structural requirements to be met
      for a musk odorant.

PMID- 17191834
TI  - New macrocyclic musk compounds.
AB  - The syntheses and olfactory evaluations of eight new macrocyclic musks with a 1,6
      dioxa structure (1a-d and 1'a-d) as well as of twelve optically active 3-methyl
      macrolides (5a-c and 5'a-c) are reported. These macrocycles were synthesized via
      intramolecular metathesis mediated by the Grubbs catalyst. Despite the absence of
      a C=O function, the 1,6-dioxa compounds, both unsaturated (1) and saturated (1'),
      possess musky odors similar to those of macrocyclic ketones and lactones.
      Especially 16-membered rings were found to display an intense and pleasant musk
      character. However, in the case of optically active 3-methyl macrolides (5, 5'),
      only the (R)-configured 15- and 16-membered rings had intense and pleasant musk
      notes.

PMID- 17191835
TI  - The search for new fragrance ingredients for functional perfumery.
AB  - Functional perfumery is an integral part of the fragrance business. It demands
      that the ingredients chosen for compounding withstand the aggressive nature of
      some of the bases used for soaps, detergents, softeners, bleach, and personal
      care products. The synthetic efforts in this area reported in this short personal
      account, presented in a talk at the RSC/SCI conference Flavours & Fragrances 2004
      (Manchester), have resulted in the discovery of the two new proprietary molecules
      Fleuranil (5/6) and Khusinil (7), which fulfill the criteria of functional
      perfumery. The structure-odor relationships of several analogs of Fleuranil and
      Khusinil prepared in the course of these investigations are also presented.

PMID- 17191837
TI  - Studies on the volatile compounds of roasted spotted shrimp.
AB  - The aroma of spotted shrimp (Sergia lucence Hansen) was analyzed upon roasting to
      determine the components that constitute the characteristic roasted shrimp
      flavor. Our analyses resulted in the identification of ca. 200 volatiles,
      including high-impact sulfur and nitrogen compounds. In addition, we synthesized
      all possible stereoisomers of the pyrrolidine derivatives 1 and 4, and of the
      imine derivatives 16 and 18-20, which are very characteristic for the aroma. The
      odor evaluation of these chemicals revealed distinct differences, each possessing
      different aroma characteristics.

PMID- 17191836
TI  - Binding studies and computer-aided modelling of macromolecule/odorant
      interactions.
AB  - Odorant-to-biopolymer (proteins and polysaccharides) binding properties influence
      the partition coefficients of odorant/matrix mixtures and depend on the molecular
      structure of the guest and the host. While air/solvent partition coefficients of
      odorants influence the flavor intensity of compounds in the headspace above the
      solvent, more complex mechanisms are proposed for the binding of a molecule to a
      food matrix. Odorant air/solvent partition coefficients are dependent on both the
      physico-chemical properties of odorant and solvent. Binding affinities for flavor
      compounds on various biopolymers can be estimated by calculation of physico
      chemical descriptors for the odorants. Binding affinities of gamma- and delta
      lactones (C7-C11) to bovine serum albumin (BSA) and beta-lactoglobulin (BLG) were
      investigated by ultracentrifugation and equilibrium-dialysis techniques.
      Quantitative structure-activity relationships (QSAR) of lactone binding on
      proteins (BLG and BSA) were performed by the measurement of lipophilicity and H
      bond strength. Large differences in observed protein-binding properties for the
      various compounds clearly demonstrated that structure-activity relationship was
      significantly influenced by the lipophilicity of the odorant. If the structure of
      the receptor molecule is known, computational ligand-macromolecule docking
      experiments can be used to predict binding affinities for unknown compounds with
      the receptor molecule. A BLG-lactone binding position, not previously reported in
      the literature, has been identified and confirmed by competitive binding studies.
      A model has been developed to estimate the free energy of binding of odorants to
      biopolymers. Estimated free energies of binding of lactones with BLG from
      computational methods were in very good agreement with the experimentally
      obtained results.

PMID- 17191838
TI  - Fun with furans.
AB  - The aromatic furan ring is found in a wide range of aroma chemicals, especially
      those produced by the Maillard reaction. They include both low-odor materials
      such as furfural and high-impact materials such as 2-methylfuran-3-thiol. Among
      the most important are the hydroxyfuranones, especially 4-hydroxy-2,5
      dimethylfuran-3(2H)-one (HDMF, 7), which is a material of unusual reactivity.
      This contrasts with the inert character of its isomer sotolone. Furans are also
      found as trace components where they can either contribute a desirable character
      or an off-note depending on context.

PMID- 17191839
TI  - Identification of new odoriferous compounds in human axillary sweat.
AB  - 3-Hydroxy-3-methylhexanoic acid (1) and the 3-sulfanylalkan-1-ols 2-5 were
      identified to contribute to the odor of human axillary sweat. Quantitative
      analyses of axillary sweat extracts from 50 healthy men showed an unambiguous
      correlation between the detected levels of 1 and the intensity of the axillary
      odor. Chiral-GC analyses revealed 1 to be a 72:28 mixture of the (S)/(R)-isomers.
      Optically pure (S)-1 (>97% ee) emanated a strong spicy note, which recalled
      typical axillary odors. 3-Methyl-3-sulfanylhexan-1-ol (2), the enantiomeric ratio
      of which equaled that of 1, was present in greater quantity than any of the other
      3-sulfanylalkanols. Optically pure (S)-2 (>97% ee) had a strong meaty, fruity
      note, also reminiscent of axillary odor. The compounds identified, in particular
      (S)-1 and (S)-2, contribute significantly to the olfactory impression of human
      axillary odor.

PMID- 17191842
TI  - Exploratory studies to investigate a linked prebiotic origin of RNA and coded
      peptides.
AB  - An introduction to the premise that RNA and genetically coded proteins should not
      be viewed as etiologically discrete entities in the origin of life is presented.
      This premise follows from the mutual interdependence of RNA and coded proteins in
      biology and the lack of prebiotically plausible constitutional self-assembly
      processes leading to either polymeric species. The RNA:coded peptides subsystem
      and its informational core, the genetic code, are then analysed
      retrosynthetically to suggest a (replicative) synthesis involving the
      intermediacy of aminoacyl-RNA trimers (cf. Scheme 5). A number of potential
      candidate aminoacyl-RNA trimers are identified (23-26; Scheme 6) and a chemical
      strategy to assess their validity is outlined. Experimental investigation of
      potential aminoacylation chemistry, nucleobase assembly and phosphate activation
      rules out three of the trimers but suggests that 26 is worthy of further
      investigation.

PMID- 17191843
TI  - Main structural and stereochemical aspects of the antiherpetic activity of
      nonahydroxyterphenoyl-containing C-glycosidic ellagitannins.
AB  - Antiherpetic evaluation of five nonahydroxyterphenoyl-containing C-glycosidic
      ellagitannins, castalagin (1), vescalagin (2), grandinin (3), roburin B (5), and
      roburin D (7), was performed in cultured cells against four HSV-1 and HSV-2
      strains, two of which were resistant to Acyclovir. All five ellagitannins
      displayed significant anti-HSV activities against the Acyclovir-resistant
      mutants, but the monomeric structures 1-3 were more active than the dimers 5 and
      7. Vescalagin (2) stands out among the five congeners tested as the most potent
      and selective inhibitor, with an IC50 value in the subfemtomolar range and a
      selectivity index 5x10(5) times higher than that of Acyclovir. Molecular modeling
      was used to provide a rationale for the surprisingly lower activity profile of
      its epimer castalagin (1). These ellagitannins have promising potential as novel
      inhibitors in the search for non-nucleoside drugs active against Acyclovir
      resistant herpes viruses.

PMID- 17191844
TI  - A simple, non-nucleosidic base surrogate increases the duplex stability of DNA
      containing an abasic site.
AB  - Abasic sites represent a common type of lesion in DNA. If not repaired, they can
      lead to mutations during replication or to cell death. Due to their biological
      importance, there is a strong interest in methods of recognizing abasic sites in
      DNA both for diagnostic and also for potential pharmaceutical applications.
      Extended aromatic residues can have a substantial positive influence on the
      stability of double-stranded DNA containing abasic sites. We report here the use
      of a simple, non-nucleosidic phenanthrene as a base surrogate, which effectively
      enhances the duplex stability of DNA with an abasic site. The influence of the
      linker length on the stability of the duplex is investigated. Data and model
      considerations indicate that stabilization is a result of stacking interactions
      between the phenanthrene and DNA base pairs.

PMID- 17191845
TI  - Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure
      elucidations, relationship to asparagamine A, and a new biogenetic concept of
      their formation.
AB  - The alkaloids 1',2'-didehydrostemofoline (2) and 2'-hydroxystemofoline (3) from
      Stemona collinsae Craib (Stemonaceae) were studied by X-ray crystallography and
      NMR spectroscopy, and they are compared with the parent compound stemofoline (1).
      The X-ray analysis of the CH2Cl2 solvate of 2'-hydroxystemofoline (3) allowed the
      determination of the absolute configuration of this compound unequivocally,
      whereas optical rotation was used to infer the absolute configuration of 1',2'
      didehydrostemofoline (2). Based on these results, it is shown that asparagamine A
      isolated from Asparagus racemosus Willd. (Asparagaceae) is identical to 1',2'
      didehydrostemofoline obtained from S. collinsae Craib, and that the reported
      plant source of asparagamine A was most likely a Stemona species. In the context
      of the current investigations, a novel concept on the biosynthesis of Stemona
      alkaloids has been worked out and is presented here.

PMID- 17191846
TI  - Immobilized Escherichia coli BL21 as a catalyst for the synthesis of adenine and
      hypoxanthine nucleosides.
AB  - Different supports, such as alginate, agar, agarose, and polyacrylamide, were
      used to immobilize Escherichia coli BL 21 by entrapment techniques. The
      transglycosylation reaction involved in the synthesis of adenosine from uridine
      and adenine was chosen as a model system to study the characteristics of these
      biocatalysts. Whole cells immobilized on agarose proved to be optimal and could
      be used up to 30 times without significant loss of activity. This biocatalyst was
      further employed to test its ability in the synthesis of other adenine and
      hypoxanthine nucleosides. Ribo-, 2'-deoxyribo-, and arabinonucleosides could be
      prepared in high yields starting from the corresponding pyrimidine nucleosides
      and purine bases. Similar product yields were obtained with both free and
      immobilized cells, though, in the latter case, a longer reaction time was
      necessary.

PMID- 17191847
TI  - Synthesis and properties of oligonucleotides carrying cryptolepine derivatives.
AB  - A carboxy derivative of the antimalarial cytotoxic drug cryptolepine was
      introduced into synthetic oligonucleotides by reaction of the carboxy derivative
      of cryptolepine with oligonucleotides carrying an amino group either at the 3'-
      or at the 5'-end. Oligonucleotides carrying the cryptolepine derivative bind
      their complementary sequences with greater affinity than unmodified ones. When
      cryptolepine is attached to a polypyrimidine oligonucleotide designed to form a
      parallel triplex, the triplex shows none or weak stabilization.

PMID- 17191848
TI  - Kinetic analysis of the reactions catalyzed by histidine and phenylalanine
      ammonia lyases.
AB  - Although both the structures and the reactions of histidine and phenylalanine
      ammonia lyases (HAL and PAL) are very similar, the former shows a primary kinetic
      deuterium (D) isotope effect, while the latter does not. In the HAL reaction, the
      release of ammonia is partially rate-determining and is slower than the release
      of the product (E)-urocanate (4), whereas in the PAL reaction, the release of (E)
      cinnamate (2) is the rate-limiting step. With (2S,3S)-[3-(2)H1]phenylalanine
      (1a), we determined the kinetic D isotope effects with the PAL mutants Q487A,
      Y350F, L137 H, and the double mutant L137 H/Q487E. The kH/kD values for the
      former two were of the same magnitude as with wild-type PAL (1.20+/-0.07), while
      the exchange of L137 to H almost doubled the effect (kH/kD=2.32+/-0.01). We
      conclude that L137 is part of the hydrophobic pocket harboring the phenyl group
      of the substrate/product and is responsible for its strong binding. The stability
      of the HAL ammonia complex was demonstrated 40 years ago. Here, we show that, in
      contrast to the former assumption, ammonia in the complex is not covalently bound
      to the prosthetic electrophile, 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO;
      5). We carried out experiments with a mutant enzyme lacking MIO and exhibiting
      ca. 10(3) times less activity. Nevertheless, the enzyme-ammonia complex was
      formed, and the mutant behaved upon addition of (E)-[14C]urocanate (4a) like wild
      type HAL. We conclude, therefore, that ammonia is bound in the complex by Coulomb
      forces as ammonium ion and can be released only after (E)-urocanate (4).

PMID- 17191849
TI  - Metapleural- and postpharyngeal-gland secretions from workers of the ants
      Solenopsis invicta and S. geminata.
AB  - Chemical analyses by GC-MS of the metapleural glands (MG) from workers of
      Solenopsis invicta and S. geminata revealed for the first time the chemical
      composition of these glands and showed small differences between the two species.
      The MG of both species contain oleic, stearic, linoleic, and palmitic acid. Both
      ants, in addition, have small but significant amounts of hydrocarbons in their MG
      reservoir, which are the same as those found in their postpharyngeal glands
      (PPG). The PPG of both species contain alkanes, alkenes, and Me-branched alkanes.
      Each species is characterized by a specific composition of PPG chemicals with
      some overlap between species. These results suggest that the MG synthesizes
      mainly palmitic, linoleic, oleic, and stearic acids in these two ants, whereas
      PPG contains hydrocarbon mixes that widely vary between these two
      phylogenetically related species.

PMID- 17191850
TI  - Complexity analysis of yeast proteome network.
AB  - Topological and compositional complexity of protein-protein networks is assessed
      in a variety of ways making use of graph theory and information theory. The
      methodology used is borrowed from mathematical chemistry and includes complexity
      descriptors such as substructure count, overall connectivity, walk count, and
      information on various vertex distributions. The approach is applied to the
      (incomplete) proteome of Saccharomyces cerevisiae containing 232 protein
      complexes of a total of 1,440 proteins. The proteome network and each of its nine
      functional subsets of protein complexes are disconnected graphs, containing a
      number of noninteracting species and a major component. A weighted edge between
      two vertices in these graphs stands for the number of shared proteins between the
      respective complexes. The major component is a highly connected, 'small-world'
      network, in which the average vertex distance between protein complexes does not
      exceed 2.2 (2.4 for the entire proteome), whereas the maximum distance does not
      exceed 4 (or 5 for the proteome). The vertex degree distribution in the major
      proteome component with 199 complexes follows the power law P(k) approximately k(
      gamma), with gamma approximately = 1.7. The analysis of the functional
      organization of the yeast proteome has shown that, for any pair of biological
      functions, there always exist many proteins that can perform both functions. The
      potential application of the quantitative proteome descriptors discussed includes
      quantitative relationships between the structure and biological action of dynamic
      protein complexes in changing environment, identification of targets for
      markers/drugs, as well as system analysis and comparative studies of proteomes.

PMID- 17191851
TI  - Synthesis and biological evaluation of paclitaxel-thiocolchicine hybrids.
AB  - The bifunctional taxoid-colchicinoid hybrids 6-8 were synthesized and evaluated
      in assays of cytotoxicity and tubulin assembly/disassembly. All compounds showed
      a high degree of cytotoxicity, but, while 6 and 7 behaved as bifunctional tubulin
      binders not unlike an equimolecular mixture of taxol and thiocolchicine, 8 was
      surprisingly devoid of tubulin activity, acting on a distinct and yet to identify
      molecular target.

PMID- 17191852
TI  - Amphotericin B covalent dimers bearing a tartarate linkage.
AB  - Amphotericin B (AmB, 1) is known to assemble together and form an ion channel
      across biomembranes, by which the drug presumably exerts its antimicrobial
      activity. To access the whole architecture of this channel assemblage, the
      understanding of binary interaction between AmB molecules is of prime importance
      because the dimeric interaction is the basis of the assemblage. In this context,
      we have recently reported covalently conjugated AmB dimers such as 2 and 3 with a
      long linker, which show prominent hemolytic potency and ion-channel activity. To
      evaluate the effect of the length and hydrophilicity of linker parts on the
      activity, we prepared new dimers bearing tartarate linkages (4 and 5).
      Especially, 5 exhibited potent hemolytic activity (EC50, 0.03 microM) surpassing
      those of AmB, 2, and 3. Measurements of UV and CD spectra of 5 in liposomes
      indicated that AmB portions of 5 could adopt appropriate arrangements in
      molecular assemblage in spite of the short linkage, and also indicated that the
      assemblage formed by 5 appeared more stable than AmB. These short-tethered dimers
      are expected to be a promising tool to reveal the mechanism of dimeric
      interaction in the ion channel formed by AmB.

PMID- 17191853
TI  - Eudesmane derivatives from Hieracium intybaceum.
AB  - Two new eudesmanolides, 4beta-H,3beta-(beta-D-glucopyranosyloxy)eudesma-1,11(13)
      dien-12,6-olide (5a) and 3beta-D-glucopyranosyloxyeudesma-1,4(15),11(13)-trien
      12,6-olide (5b), as well as two related, known compounds, tuberiferin (7a) and
      dehydrobrachylaenolide (7b), were isolated from the CH2Cl2 extract of subaerial
      parts of Hieracium intybaceum All. Compounds 6a, 6b, 8a, and 8b, the Me esters of
      the corresponding sesquiterpenic acids related to 5a, 5b, 7a, and 7b,
      respectively, were obtained as artifacts during the isolation process.
      Additionally, linoleic acid (1), linolenic acid (2), the lignane syringaresinol
      4'-O-beta-D-glucopyranoside (3), and the guaianolide dehydrocostus lactone (4)
      were also isolated from H. intybaceum. Structure elucidations were based on mass
      spectrometry and extensive 1D- and 2D-NMR spectroscopy.

PMID- 17191854
TI  - The chemodiversity of purine as a constituent of natural products.
AB  - In this review, I describe various natural manifestations of purine systems,
      i.e., methylated, higher-alkylated, and glycosylated forms. These comprise the
      purine alkaloids, cytokines, as well as the purine nucleoside antibiotics. In
      part, the compounds described herein were isolated from natural sources already
      long ago. However, some have been reported only during the last few years. The
      biological activities of most of the purine derivatives are briefly described,
      and, in some cases, syntheses are formulated. In particular, this article
      introduces the main synthetic principles for the generation of the purine ring
      system. The last chapter describes modern preparative routes for C-alkylation and
      C-arylation of purines.

PMID- 17191855
TI  - 'Ethylene-bis[phosphonate] nucleic acids': novel monomeric synthons for the solid
      phase synthesis of (P-CH2-CH2-P)-bridged oligonucleotides.
AB  - An efficient synthesis of modified deoxyribonucleosidic building units,
      containing the 'ethylene-bisphosphonate nucleic acids' (EBPNAs) 1 or 2, has been
      developed. By means of solution-phase incorporation of 11, the oxidized form of
      2, dinucleotide analogs of type 13 were prepared. The same strategy was used to
      incorporate 2 into the 5'-terminal position of the 12-mer homopolynucleotide
      methylphosphonate 14. A preliminary approach for solid-phase incorporation of the
      nucleosidic building block 1 into a preselected position of an oligonucleotide
      sequence to give 19 is presented, a reaction performed by means of a coupling
      strategy involving catalytic oxazaphospholidine-ring cleavage.

PMID- 17191856
TI  - Polyphenols from Polygala spp. and their antioxidant activity.
AB  - Members of Polygalaceae are known to contain a variety of different polyphenolic
      compounds such as xanthones, flavonoids, and biphenyl derivatives. Here, we
      report the isolation and structural characterization of two new phenol
      derivatives, named alpestrin (= 3,3',5'-trimethoxy[1,1'-biphenyl]-4-ol; 10) and
      alpestriose A (= 6-O-benzoyl-1-O-{6-O-acetyl-3-O-[(4-hydroxy-3,5
      dimethoxyphenyl)prop-2-enoyl]-beta-D-fructofuranosyl}-alpha-D-glucopyranoside;
      11), and of four known compounds (12-15) from the MeOH extract of Polygala
      alpestris. The relative in vitro antioxidant activities of these compounds, in
      comparison with other phenolic substances from Polygala vulgaris, were evaluated
      by means of the Briggs-Rauscher (BR) oscillating reaction, a method based on the
      inhibitory effects of antioxidant free-radical scavengers. The experimental
      antioxidant-activity values (relative to resorcinol as a standard) were compared
      with those calculated on the basis of the bond-dissociation enthalpies. The
      structure/activity relationships for the compounds examined are also discussed.

PMID- 17191857
TI  - Novel lipid-peroxidation- and cyclooxygenase-inhibitory tannins from Picrorhiza
      kurroa seeds.
AB  - From the AcOEt extract of the seeds of Picrorhiza kurroa were isolated picrorhiza
      acid (1), picrorhizoside A (2), picrorhizoside B (3), picrorhizoside C (4), (-)
      shikimic acid (5), gallic acid (6), ellagic acid (7), isocorilagin (8), 1-O
      galloyl-beta-D-glucose (9), 1-O,3-O,6-O-trigalloyl-beta-D-glucose (10), and 1-O,2
      O,3-O,4-O,6-O-pentagalloyl-beta-D-glucose (11), and their structures were
      established by extensive NMR and chemical studies. Constituents 1-4 are novel
      compounds, and the known compounds 5-11 have been isolated for the first time
      from the seeds of P. kurroa. Compounds 2 and 3 were hydrolyzed and yielded 12,
      isochebulic acid. Compounds 1-12 showed 89.6, 77.3, 56.1, 50.5, 11.0, 86.4, 50.5,
      29.2, 70.9, 50.5, 56.5, and 86.1% inhibition of lipid peroxidation at 5
      microg/ml, respectively. The commercial antioxidants BHA (1.8 microg/ml), BHT
      (2.2 microg/ml), and TBHQ (1.66 microg/ml) inhibited lipid peroxidation at 85.6,
      87.1, and 81.1%, respectively. The inhibition of cyclooxygenase-1 (COX-1) by 2-5,
      7, 8, and 10-12 at 100 microg/ml was 41.9, 28.4, 32.9, 9.3, 70.7, 34.7, 16.0,
      89.6, and 53.4%, respectively. Similarly, compounds 1-8 and 11 and 12, at 100
      microg/ml, inhibited COX-2 by 12.6, 15.3, 25.1, 5.3, 13.2, 21.7, 2.0, 42.4, 43.4,
      and 36.9%, respectively.

PMID- 17191858
TI  - Peptide-biphenyl hybrids as calpain inhibitors.
AB  - Calpain is a cysteine protease that is activated by Ca2+. The over-activation of
      calpain, which occurs on increasing Ca2+ concentration, causes a variety of
      diseases. This paper reports experimental results on the inhibition of calpain I
      (mu-calpain) by peptide-biphenyl hybrids. We have found that some peptide
      biphenyl hybrids, with aromatic amino acids in the peptide chains, inhibit
      calpain with IC50 values in the nanomolar range. Since the peptide-biphenyl
      hybrids reported in the present paper do not possess a reactive electrophilic
      functionality, we hypothesize that they interfere with the activation of calpain
      by Ca2+, and present experimental and computational results on the binding of
      peptide-biphenyl hybrids to Ca2+.

PMID- 17191859
TI  - Limbetazulone: a new 'decahydro-8-oxanaphtho[2,1-f]azulen-7-one' diterpenoid from
      Ballota limbeta, and occurrence of two conformational isomers in the crystal.
AB  - A new diterpenoid, limbetazulone (= (3S,4S,4aR,12bS)-1,2,3,4,4a,5,6,11,12,12b
      decahydro-3-hydroxy-4-(hydroxymethyl)naphtho[1',2': 5,6]cyclohepta[1,2-b]furan
      7(7H)-one; 1), with the very rare 'naphtho[2,1-f]azulene-7-one' skeleton, was
      isolated from the aerial parts of the Asian medicinal plant Ballota limbeta. Its
      structure was established by extensive spectroscopic investigations, especially
      1D and 2D NMR. X-Ray diffraction studies showed the presence of two
      conformational isomers (1a and 1b) in the crystal.

PMID- 17191860
TI  - Extracts and sesquiterpene derivatives from the red alga Laurencia chondrioides
      with antibacterial activity against fish and human pathogenic bacteria.
AB  - During screening of seaweeds from different places in Europe for antimicrobial
      activities against human and fish pathogenic bacteria, Laurencia chondrioides was
      identified as a promising species. By bioassay-guided isolation, followed by
      structure elucidation by mass spectrometry and 1H- and 13C-NMR spectrometry, two
      sesquiterpenoides of the chamigrene-type from the selected red seaweed Laurencia
      chondrioides were identified. Both compounds inhibit the growth of some fish and
      human pathogenic bacteria.

PMID- 17191861
TI  - Associating hyaluronan derivatives: a novel horizon in viscosupplementation of
      osteoarthritic joints.
AB  - The association of two high-molecular-weight hyaluronan (HA) derivatives, namely
      a beta-cyclodextrin (HA-beta-CD) and an N-acylurea (EDC-HA), dissolved in aqueous
      NaCl, was studied. The weight-average of the molecular weights (Mw) of HA-beta-CD
      and of EDC-HA was 185.3 and 86.8 kDa, respectively. However, the Mw value
      determined for the equimolar mixture of the two biopolymers equaled 556.0 kDa.
      Similarly, the radius of gyration (dimension) Rg = 80.6 nm of the above equimolar
      mixture was significantly greater than the values found for the single
      macromolecules, i.e., 40.2 nm for HA-beta-CD and 23.8 nm for EDC-HA. These data
      indicate that the two kinds of substituents, borne by the HA polymeric chains,
      form host-guest inclusion complexes resulting in polymacromolecular
      associates/aggregates.

PMID- 17191862
TI  - Guanine 6-O-methylation pattern within the dioxin responsive element of the
      CYP1A1 enhancer shows two critical guanines for AhR/ARNT binding.
AB  - The core-recognition motif for TCDD-liganded AhR/ARNT complex of the dioxin
      responsive element (DRE) contains four guanine residues, three on the antisense
      (5'-T(T)/(A)GCGTG-3') and one on the sense (5'-CACGC(A)/(T)A-3') strand. It has
      been reported that, in methylation-protection and methylation-interference
      assays, the TCDD-liganded AhR/ARNT contacts all four guanine residues. On the
      other hand, it is known that some anticancer drugs, and various environmental and
      workplace chemicals, including strongly human carcinogenic nitrosamines, lead to
      the highly miscoding 6-O-methylation of guanine. In the present study, we have
      investigated whether specific methylation of guanine at the 6-O-position
      interferes with the binding of TCDD-liganded AhR/ARNT complex to its recognition
      motif in the CYP1A1 enhancer, and how individual 6-O-methylated guanines
      contribute to this interference. We found that only two 6-O-methylguanine
      residues are critical: the closest to the 5'-end within the three-nucleotide
      sequence (5'-GTG-3'), identical to a half-site E-box element, on the antisense
      strand, and the only guanine on the sense strand. In contrast, the 6-O
      methylguanine closest to the 5'-end (well) and the one closest to the 3'-end (to
      a lesser extent), both on the antisense strand, were still able to bind the TCDD
      liganded AhR/ARNT complex. This shows that the 6-O-methylation of guanine in the
      core sequences of CYP1A1 enhancer interferes with the binding of the ligand
      activated AhR/ARNT complex in a differentially selective manner; it fully impedes
      binding of this complex to DRE (the prerequisite of most of the toxic effects of
      TCDD) only when one of the two particular guanines is methylated at the 6-O
      position.

PMID- 17191863
TI  - Diastereoisomer-selective inclusion complexation of Cinchona alkaloids with a
      modified beta-cyclodextrin: fluorescent behavior enhanced by chiral-tether
      binding. Short communication.
AB  - The molecular 1:1 complexation of cinchona alkaloids by mono(6-deoxy-6-{[(R)-1
      (hydroxymethyl)propyl]amino})-beta-cyclodextrin (1) in aqueous solution has been
      investigated by 2D-NMR, fluorescence titration, and fluorescence-lifetime
      experiments. Generally, with 1 as the host, in contrast to beta-cyclodextrin
      proper, strong binding of quinine (2; Ka = 84,200 M(-1)) and quinidine (3; Ka =
      27,300 M(-1)) at pH 6.8 was observed, as monitored by an increase in fluorescence
      intensity, with a fair degree of diastereoisomer discrimination (ca. 3:1). To
      rationalize these results, two possible cooperative complexation modes, including
      specific H-bonding interactions to the chiral tether of the cyclodextrin portion,
      are proposed.

PMID- 17191864
TI  - Two novel hexadepsipeptides with several modified amino acid residues isolated
      from the fungus Isaria.
AB  - Two new cyclohexadepsipeptides have been isolated from the fungus Isaria. Fungal
      growth in solid media yielded hyphal strands from which peptide fractions were
      readily isolable by organic-solvent extraction. Two novel cyclodepsipeptides,
      isaridin A and isaridin B, have been isolated by reverse-phase HPLC, and
      characterized by ESI-MS and 1H-NMR. Single crystals of both peptides have been
      obtained, and their 3D structures were elucidated by X-ray diffraction. The
      isaridins contain several unusual amino acid residues. The sequences are
      cyclo(beta-Gly-HyLeu-Pro-Phe-NMeVal-NMePhe) and cyclo(beta-Gly-HyLeu-beta-MePro
      Phe-NMeVal-NMePhe), where NMeVal is N-methylvaline, NMePhe N-methylphenylalanine,
      and HyLeu hydroxyleucine (= 2-hydroxy-4-methylpentanoic acid). The two peptides
      differ from one another at residue 3, isaridin A having an (S)-proline at this
      position, while beta-methyl-(S)-proline (= (2S,3S)-2,3,4,5-tetrahydro-3-methyl-1H
      pyrrole-2-carboxylic acid) is found in isaridin B. The solid-state conformations
      of both cyclic depsipeptides are characterized by the presence of two cis peptide
      bonds at HyLeu(2)-Pro(3)/HyLeu(2)-beta-MePro(3) and NMeVal(5)-NMePhe(6),
      respectively. In isaridin A, a strong intramolecular H-bond is observed between
      Phe(4)CO...HNbeta-Gly(1), and a similar, but weaker, interaction is observed
      between beta-Gly(1)CO...HNPhe(4). In contrast, in isaridin B, only a single
      intramolecular H-bond is observed between beta-Gly(1)CO...HNPhe(4).

PMID- 17191865
TI  - Modelling of the complex between a 15-residue peptide from mSos2 and the N
      terminal SH3 domain of Grb2 by molecular-dynamics simulation.
AB  - Under specific conditions, the complex formed by the adaptor protein Grb2 and the
      guanine-nucleotide exchange factor Sos2 is responsible for the activation of Ras,
      a low-molecular-weight GTPase involved in the control of cell proliferation and
      differentiation. The interaction between the N-terminal SH3 domain of the mouse
      Grb2 and one of its potential target sequences in the mouse, Sos2, a 15-residue
      peptide corresponding to residues 1264-1278, had been studied by NMR. However,
      the resulting data provided very limited information on the structure of the
      peptide and its interaction with the protein. Here, we present results from a
      molecular-dynamics simulation aimed at producing a realistic, atomic model for
      the interaction between the N-terminal SH3 domain of Grb2 and the SPLLPKLPPKTYKRE
      peptide from Sos2. In the simulation, the peptide adopts an extended conformation
      over the protein's binding surface. The proposed polyproline-type-II helicity
      appears only locally, and the peptide displays substantial flexibility. It is
      found that the peptide residues Lys10 to Tyr12 could be responsible for most of
      the specificity of the interaction.

PMID- 17191866
TI  - Polysaccharide/polynucleotide complexes. Part 6: complementary-strand-induced
      release of single-stranded DNA bound in the schizophyllan complex.
AB  - Spectroscopic properties of single-stranded DNA/schizophyllan ternary complexes
      (ss-DNA2s-SPG), induced by addition of either complementary or noncomplementary
      strands, have been investigated. The addition of the complementary strands to ss
      DNA2s-SPG induced the quick release of the bound ss-DNA to the complementary
      strands (both DNA and RNA), whereas the ternary complex was unaffected upon
      addition of noncomplementary strands. Our experiments imply that SPG has
      complexation properties indispensable to the gene carriers. As far as we know,
      there is no report on exploitation of such nonviral gene carriers that can
      accomplish an intelligent release of the bound ss-DNA toward the complementary
      strands. We believe, therefore, that SPG, a natural and neutral polysaccharide,
      has a great potential to become a new ss-DNA carrier.

PMID- 17191867
TI  - Antimicrobial and cytotoxic activities of neolignans from Magnolia officinalis.
AB  - In the light of the steady increase of infections related to vancomycin-resistant
      enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), the
      medicinal plant Magnolia officinalis was subjected to bioassay-directed
      fractionation, which led to the isolation of the known neolignans
      piperitylmagnolol (1), magnolol (2), and honokiol (3) from the MeOH extract. In
      broth-microdilution assays, 1-3 exhibited antibacterial activities against VRE
      and MRSA at minimum-inhibitory concentrations (MIC) in the range of 6.25-25
      microg/ml, compound 1 being the most-potent antibiotic. The ratio of MBC/MIC (MBC
      = minimum bactericidal concentration) was < or = 2 for all compounds. The
      kinetics of the antibacterial action of 1 and 3 were studied by means of time
      kill assays; both compounds were bactericidal against VRE and MRSA, their actions
      being time dependent, or both time and concentration dependent. Magnolol (2) was
      acetylated to magnolol monoacetate (4) and magnolol diacetate (5) (partial or
      full masking of the phenolic OH functions). The cytotoxic properties of 1-5
      against human OVCAR-3 (ovarian adenocarcinoma), HepG2 (hepatocellular carcinoma),
      and HeLa (cervical epitheloid carcinoma) cell lines were evaluated. The CD50
      values for compounds 1-3 were in the range of 3.3-13.3 microg/ml, derivatives 4
      and 5 being much less potent. This study indicates that piperitylmagnolol (= 3
      [(1S,6S)-6-isopropyl-3-methylcyclohex-2-enyl]-5,5'-di(prop-2-enyl)[1,1'-biphenyl]
      2,2'-diol; 1) possesses both significant anti-VRE activity and moderate
      cytotoxicity against the above cancer cell lines.

PMID- 17191868
TI  - Natural-product diversity of the New Caledonian marine ecosystem compared to
      other ecosystems: a pharmacologically oriented view.
AB  - In comparison with other ecosystems, biodiversity and natural-product diversity
      of the New Caledonian marine ecosystem, comprising lagoons, barrier reefs, and
      deep waters in seamount regions, are described here phylogenetically with the aid
      of molecular drawings and tabulation of data. Admittedly, since the inception of
      these studies in 1977, the comparison is biased by selection of New Caledonian
      organisms on the basis of positive pharmacologically oriented bioassays. However,
      we show that these and other distortions must be accepted to draw any comparison
      on a regional basis, which, nonetheless, turn out to be useful for the progress
      of knowledge, particularly in directing future explorations of biodiversity in
      the search for new pharmacologically active metabolites.

PMID- 17191869
TI  - Synthesis of encoded modified oligonucleotide libraries. Part 1: orthogonal
      chemistry.
AB  - The basis for further development of combinatorial libraries of modified
      oligonucleotides tagged by a codifying sequence is discussed. The chemistry
      involved in the orthogonal synthesis of both strands and some representative
      examples of building blocks are presented.

PMID- 17191871
TI  - Quantity over quality? An open letter to the community of chemists.

PMID- 17191870
TI  - DPPH radical scavenging activity of ten natural p-terphenyl derivatives obtained
      from three edible mushrooms indigenous to China.
AB  - The antioxidant activities of ten natural p-terphenyl derivatives, 1-10, obtained
      from the fruiting bodies of three edible mushrooms (Thelephora ganbajun,
      Thelephora aurantiotincta, Boletopsis grisea) indigenous to China were evaluated
      in comparison with BHA ('butylated hydroxyanisole'=(1,1-dimethylethyl)-4
      methoxyphenol) and alpha-tocopherol by the DPPH ('1,1-diphenyl-2
      picrylhydrazyl'=2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl) radical-scavenging
      method. The compounds 1-3 showed significant antioxidant activity. The
      antioxidant activities of compounds 1-10 and reference compounds followed the
      order: 2>BHA>1>3>alpha-tocopherol>10>9>6 > 5>8>7>4. The compound 2 exhibited the
      strongest radical-scavenging activity with an EC(50) value of 0.07 (EC(50)(BHA)
      0.09; EC(50)(alpha-tocopherol) 0.25).

PMID- 17191872
TI  - Selective circular oligonucleotide probes improve detection of point mutations in
      DNA.
AB  - The synthesis of disulfide-cross-linked circular oligonucleotides, employing two
      different approaches, was accomplished. Several circular oligomers, which bear a
      C(5)-aminoalkyl-tethered thymidine unit, were labeled with photoluminescent
      europium(III) chelates. All circular structures were thoroughly characterized
      with denaturing PAGE and electrospray-ionization mass spectrometry. It was
      demonstrated that the disulfide cross-linking, resulting in circularization,
      considerably increases the enzymatic stability of phosphodiester
      oligonucleotides. In addition, UV melting experiments, followed, where possible,
      by extraction of thermodynamic parameters, revealed that several circular
      oligomers appear to be more selective towards their complementary targets than
      their corresponding linear precursors. Finally, the mixed-phase hybridization
      experiments have demonstrated that use of circular probes indeed improves the
      selectivity in the detection of DNA point mutations.

PMID- 17191874
TI  - First observation by fluorescence polarization of complexation between mRNA and
      the natural polysaccharide schizophyllan.
AB  - Schizophyllan is a natural beta-(1-->3)-D-glucan that exists as a triple helix in
      H(2)O and as a single chain in dimethylsulfoxide (DMSO) or basic solution (pH
      >13). As we have already reported, when a homo-polynucleotide (e.g., poly(dA),
      poly(A), or poly(C)) is added to a schizophyllan/DMSO solution, and,
      subsequently, DMSO is exchanged for H(2)O, the single chain of schizophyllan
      forms a complex with the polynucleotide. Since eukaryotic mRNAs have poly(A)
      tails, we hypothesized that schizophyllan can bind to mRNA by interacting with
      this tail. However, we have not yet observed complexation between schizophyllan
      and mRNA after exchanging DMSO for H(2)O. In this report, we show that the
      complexation can be accelerated when the solution pH is changed from 13 to 7-8 in
      the presence of schizophyllan and polynucleotides. By this approach, we found
      that schizophyllan forms a complex with a yeast mRNA.

PMID- 17191873
TI  - Enantioselective synthesis of (S)-3-carboxy-4
      ((carboxy)difluoromethyl)phenylalanine in protected form and its incorporation
      into a PTP-1B-directed tripeptide.
AB  - Recent findings have shown that, when expressed in the tripeptide platform, 'Fmoc
      Glu-Xxx-Leu-amide', the phosphotyrosyl mimetic (pTyr), Xxx=(S)-3-carboxy-4
      (carboxymethyl)-Phe, provides higher PTP-1B affinity than that obtained with
      Xxx=(S)-difluorophosphonomethyl-Phe (F(2)Pmp). This was of note, since
      difluorophosphonomethyl-containing pTyr mimetics have typically exhibited higher
      PTP-inhibitory potencies than carboxy-based mimetics, indicating the potential
      value of 3-carboxy-4-(carboxymethyl)-Phe as a starting point for further analogue
      development. Therefore, relying on precedence that alpha-fluorination often
      enhances PTP-1B affinity, (S)-3-carboxy-4-((carboxy)difluoromethyl)-Phe was
      designed as a PTP-1B-directed pTyr mimetic. Reported herein is the synthesis of
      this new amino acid analogue through application of commercially available
      Williams chiral auxiliary. The target was prepared in an orthogonally protected
      form suitable for peptide synthesis according to Fmoc chemistries and utilization
      for the synthesis of a PTP-1B-directed tripeptide bearing the sequence indicated
      above. Biological evaluation with in vitro PTP-1B assays indicated nearly total
      loss of affinity for this peptide. Evidence is provided that the unexpected
      deleterious effect of fluorination is probably not related to pK(a) effects.

PMID- 17191875
TI  - Micromonosporin A, a novel 24-membered polyene lactam macrolide from
      Micromonospora sp. isolated from peat swamp forest.
AB  - A novel 24-membered polyene lactam macrolide, micromonosporin A
      (=(3E,5E,7Z,15E,17E,19E,21E)-9,11,13-trihydroxy-14,19,24-trimethyl-1
      azacyclotetracosa-3,5,7,15,17,19,21-heptaen-2-one; 1) was isolated from the
      actinomycete, Micromonospora sp. strain TT1-11, which was isolated from a very
      acidic peat swamp forest.

PMID- 17191876
TI  - Biologically active ibogan and vallesamine derivatives from Tabernaemontana
      divaricata.
AB  - Six new indole alkaloids, viz., (3S)-3-cyanocoronaridine (2), (3S)-3
      cyanoisovoacangine (3), conolobine A (5), conolobine B (6), conolidine (7), and
      (3R/3S)-3-ethoxyvoacangine (8), in addition to 36 known ones, were obtained from
      the stem-bark extract of the Malayan Tabernaemontana divaricata. The structures
      were determined by NMR and MS analysis. The CN-substituted alkaloids showed
      appreciable cytotoxicity towards the KB human oral epidermoid carcinoma cell
      line.

PMID- 17191877
TI  - Chlorophyll breakdown in tobacco: on the structure of two nonfluorescent
      chlorophyll catabolites.
AB  - In extracts of senescent leaves of the tobacco plant Nicotiana rustica, two
      colorless compounds with UV/VIS characteristics of nonfluorescent chlorophyll
      catabolites (NCCs) were detected and tentatively identified as Nr-NCCs. These two
      polar NCCs were found in similar amounts in the fresh extracts, and their
      constitutions could be determined by spectroscopic analysis. The data showed both
      of the two Nr-NCCs to have the same tetrapyrrolic core structure, as reported
      previously for all other NCCs from senescent higher plants. In the less polar
      catabolite, named Nr-NCC-2, this core structure was conjugated with a
      glucopyranose unit, as similarly discovered earlier in Bn-NCC-2, an NCC from
      oilseed rape (Brassica napus). The more polar NCC from tobacco leaves, Nr-NCC-1,
      carried an additional malonyl substituent at the 6'-OH group of the
      glucopyranosyl moiety. Partial (enzyme-catalyzed) hydrolysis of Nr-NCC-1 gave Nr
      NCC-2, while enzyme-catalyzed malonylation of Nr-NCC-2 gave Nr-NCC-1,
      establishing the identity of their basic tetrapyrrole structure. In earlier work
      (on the polar NCCs from oilseed rape), only separate glucopyranosyl and malonyl
      functionalities were detected. Nr-NCC-1, thus, represents a further variant of
      the structures of NCCs from senescent higher plants and exhibits an unprecedented
      peripheral refunctionalization in chlorophyll catabolites.

PMID- 17191878
TI  - International Union of Pure and Applied Chemistry [IUPAC]: recommendations for
      global cooperation on sustainable prospecting for molecular systems and
      information at the molecular level derived from natural resources.

PMID- 17191879
TI  - Chemistry and biodiversity of the biologically active natural glycosides.
AB  - This review covers the literature on isolation, bioactivities, and structures of
      nearly 800 natural glycosides.

PMID- 17191880
TI  - Photophysical and phototoxic properties of the antibacterial fluoroquinolones
      levofloxacin and moxifloxacin.
AB  - Two antibacterial fluoroquinolones, levofloxacin and moxifloxacin, were
      investigated to evaluate their photophysical properties and to explore the
      mechanism of their phototoxicity. Photophysical experiments were carried out in
      aqueous solution by stationary and time-resolved fluorimetry, and by laser flash
      photolysis, to obtain information on the various decay pathways of the excited
      states of the drugs and on transient species formed upon irradiation. The results
      obtained show that levofloxacin is able to photosensitize red blood cell lysis in
      an oxygen-independent way and induce a high decrease in cell viability after UVA
      irradiation, although to a lesser degree than the racemic mixture ofloxacin.
      Moxifloxacin, which is an 8-MeO-substituted fluoroquinolone, is less phototoxic
      than the other compounds. Cellular phototoxicity was inhibited by the addition of
      superoxide dismutase, catalase, and free radical and hydroxyl radical scavengers
      (BHA, GSH, mannitol, and DMTU), indicating the involvement of superoxide anion
      and/or a radical mechanism in their cytotoxicity. A good correlation was observed
      between lipid peroxidation, protein photodamage, and cellular phototoxicity,
      indicating that test compounds exert their toxic effects mainly in the cellular
      membrane. Experiments carried out on pBR322 DNA show that these derivatives do
      not significantly photocleave DNA directly, but single-strand breaks were
      evidenced after treatment of photosensitized DNA by two base-excision-repair
      enzymes, and Endo III.

PMID- 17191881
TI  - Stability and dynamics of domain-swapped bovine-seminal ribonuclease.
AB  - The proteins of the ribonuclease-A (RNase-A) family are monomeric, with the
      exception of bovine-seminal ribonuclease (BS-RNase). BS-RNase is formed by
      swapping the N-terminal helices across the two monomeric units. A molecular
      dynamics (MD) study has been performed on the protein for a simulation time of
      5.5 ns to understand the factors responsible for the stability of the dimer.
      Essential dynamics analysis and motional correlation of the protein atoms yielded
      the picture of a stabilising, yet flexible, interface. We have investigated the
      role of intermolecular H-bonding, protein/water interaction, and protein/water
      networks in stabilising the dimer. The networks of interchain H-bonds involving
      side-chain/side-chain or side-chain/main-chain (ScHB) interactions between the
      two chains have also been studied. The ability of protein atoms in retaining
      particular H2O molecules was investigated as a function of the accessible surface
      area (ASA), depth, and hydration parameters, as well as their participation in
      protein/water networks.

PMID- 17191882
TI  - Screening of non-alkaloidal natural compounds as acetylcholinesterase inhibitors.
AB  - Acetylcholinesterase (AChE) inhibitors are currently the only approved therapy
      for the treatment of Alzheimer's disease, only a limited number of drugs are
      commercially available. A library of non-alkaloidal natural compounds was
      investigated. To this end, a convenient microtitre plate method for assaying AChE
      inhibition, which allows a complete kinetic analysis of AChE inhibitors, was
      developed. Seven active compounds with Ki values in the micromolar range were
      identified, six of which were xanthones. This is the first report that a
      promising potential for AChE inhibition exists in such non-nitrogenous natural
      compounds. Furthermore, four xanthones among these xanthones had already been
      described as monoamine oxidase (MAO) inhibitors, making then dual AChE/MAO
      inhibitors of great interest.

PMID- 17191883
TI  - Structure determination of an organometallic 1-(diazenylaryl)ethanol: a novel
      toxin subclass from the web of the spider Nephila clavipes.
AB  - A novel chemical subclass of toxin, [1-(3-diazenylphenyl)ethanol]iron, was
      identified among the compounds present in the web of the spider Nephila clavipes.
      This type of compound is not common among natural products, mainly in spider
      venom toxins; it was shown to be a potent paralytic and/or lethal toxin applied
      by the spider over its web to ensure prey capture only by topical application.
      The structure was elucidated by means of ESI mass spectrometry, 1H-NMR
      spectroscopy, high-resolution (HR) mass spectrometry, and ICP spectrometry. The
      structure of [1-(3-diazenylphenyl)ethanol]iron and the study of its insecticidal
      action may be used as a starting point for the development of new drugs for pest
      control in agriculture.

PMID- 17191884
TI  - Copper(II) complexes containing N,N-donor ligands and dipeptides act as
      hydrolytic DNA-cleavage agents.
AB  - Copper(II) complexes are known to play a significant role in both naturally
      occurring biological systems and pharmaceutical agents. Recently, Cu(II)
      complexes have gained importance in DNA cleavage essential for the development of
      anticancer drugs and chemotherapeutic agents. Therefore, we have designed small
      molecules, consisting of a metal ion, N,N-donor ligands, and dipeptides, to probe
      their DNA-cleaving potential. Accordingly, the interaction of Cu(II) with
      ethylenediamine, histamine and the dipeptides histidylglycine, histidylalanine,
      and histidylleucine has been investigated. The binding modes, stabilities, and
      geometries of these complexes were determined by various physicochemical
      techniques. Their DNA-binding abilities were probed by absorption and
      fluorescence spectroscopy, and their DNA-cleavage potential was tested by
      electrophoresis.

PMID- 17191885
TI  - Enantiospecific syntheses of C(5)-functionalized precursors of artemisinin
      derivatives.
AB  - Enantiomerically pure compounds as precursors for the synthesis of hydroxylated
      derivatives of artemisinin/arteether have been prepared from (+)-(S)-carvone and
      (+)-car-2-ene.

PMID- 17191886
TI  - Synthesis, spectral properties, and antitumor activity of a new axially
      substituted phthalocyanine complex of zirconium(IV) with citric acid.
AB  - The new axially substituted phthalocyanine (pc) complex of zirconium(IV) with
      citric acid is reported. It has been shown that the replacement of two Cl-atoms
      with two citric acid fragments takes place as the result of the reaction between
      [ZrCl2(pc)] and citric acid. The complex [Zr(citrate)2(pc)] was formed. The
      spectroscopic properties of the synthesized compound in DMSO, RPMI 1640 medium
      with and without fetal calf serum (FCS), H2O, and buffer (Tris) solutions have
      been described. Antitumor activity of this compound has been studied. The
      cytostatic activity was observed in the concentration range of 6.1-9.0x10(9)
      molecules [Zr(citrate)2(pc)]/cell and occurred in 4-6 h after treatment with
      [Zr(citrate)2(pc)] solution.

PMID- 17191887
TI  - Characterization of serotonin in protein and membrane mimetic environments: a
      spectroscopic study.
AB  - As a first step toward using the photophysical properties of serotonin to probe
      its interactions with biological target sites, we have examined its interactions
      with human serum albumin (HSA), chosen as a surrogate for the actual receptor
      proteins in physiological systems, and with sodium bis(2
      ethylhexyl)sulfosuccinate (AOT)/heptane/water reverse micelles, chosen as a
      biomembrane mimetic environment for the transmembrane portion of the receptor
      protein. Although the emission maximum of serotonin is relatively insensitive to
      the polarity of the local environment, which is attributed to lack of solvent
      dipolar reorientation of the 5-hydroxyindole chromophore, the fluorescence
      anisotropy (r) served as a useful and sensitive parameter from which the binding
      constants (K) and Gibbs energy changes (deltaG) were estimated for serotonin-HSA
      and serotonin-AOT reverse micellar interactions. Fluorescence-decay studies of
      serotonin show double-exponential kinetics in homogeneous aqueous solvent due to
      the structural heterogeneity arising from different rotamers of serotonin. In
      contrast, upon binding to HSA, a single-exponential fluorescence-decay profile
      was observed indicating the occurrence of a single structural species of
      serotonin in the protein environment. Furthermore, far-UV-circular-dichroism (CD)
      spectroscopic data indicate that the secondary structural features of HSA remain
      essentially intact after binding to serotonin. This preliminary research can be
      expected to open the door to extensive future studies on interactions of
      serotonin with relevant target proteins and associated cell membranes involved in
      its diverse physiological functions.

PMID- 17191888
TI  - Cancer chemopreventive activity of serratane-type triterpenoids from Picea
      jezoensis.
AB  - To search for cancer chemopreventive agents from natural sources, 13alpha,14alpha
      epoxy-21alpha-methoxyserratan-3-one, 21alpha-methoxyserrat-13-en-3-one, and
      21alpha-hydroxy-3beta-methoxyserrat-14-en-30-al isolated from the cuticle of
      Picea jezoensis (Sieb. et Zucc.) Carr. var. jezoensis (Pinaceae) were
      investigated for inhibitory effects in a two-stage mouse skin carcinogenesis test
      on mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O
      tetradecanoylphorbol-13-acetate (TPA) as promoter. 21Alpha-hydroxy-3beta
      methoxyserrat-14-en-30-al and 13alpha,14alpha-epoxy-21alpha-methoxyserratan-3-one
      were found to exhibit strong antitumor-promoting activities in the in vivo
      carcinogenesis test.

PMID- 17191889
TI  - DNA minor-groove recognition by 3-methylthiophene/pyrrole pair.
AB  - Hairpin polyamides are synthetic oligomers, which fold and bind to specific DNA
      sequences in a programmable manner. Internal side-by-side pairings of the
      aromatic amino acid residues 1-methyl-1H-pyrrole (Py), 1-methyl-1H-imidazole
      (Im), and 3-hydroxy-1-methyl-1H-pyrrole (Hp) confer the ability to distinguish
      between all four Watson-Crick base pairs in the minor groove of B-form DNA. In a
      broad search to expand the heterocycle repertoire, we found that when 3
      methylthiophene (Tn), which presents a S-atom to the minor groove, is paired with
      Py, it exhibits a modest threefold specificity for TA>AT presumably by shape
      selective recognition. In this study, we explore the scope and limitations of
      this lead by incorporating multiple Tn residues within a single hairpin
      polyamide. It was found that hairpin polyamides containing more that one Tn/Py
      pair exhibit lowered affinities and specificities for their match sites. It
      appears that little deviation is permissible from the parent five-membered ring 1
      methyl-1H-pyrrole-2-carboxamide scaffold for DNA recognition.

PMID- 17191890
TI  - Enzymatic Baeyer-Villiger oxidation as the key step in decano-4-lactone and
      decano-5-lactone degradation by Sporobolomyces odorus.
AB  - The biosyntheses of aroma active gamma- and delta-lactones have been previously
      characterized in yeasts and plants by incubation of labeled fatty acid
      derivatives. The lactones were considered as end products. Liquid cultures of the
      lactone-producing yeast Sporobolomyces odorus were used to investigate catabolic
      pathways of the lactones by incubation of ethyl (+/-)-5-hydroxy(1
      (13)C1)decanoate ((13C)-1b) and methyl (+/-)-4-hydroxy(1-(13)C1)decanoate ((13C)
      7a). Aliquots of the culture broth were analyzed with GC/MS after CH2N2
      derivatization. S. odorus degraded (13C)-1b to 5-oxo(1-(13)C1)decanoic acid
      ((13C)-2c) and, subsequently, to pentyl (1-(13)C1)pentanedioate ((13C)-3c) and 3
      [(1-(13)C1)carboxypropyl] hexanoate ((13C)-4c) by a Baeyer-Villiger-type
      oxidation (BVO). In addition, the oxidation of (13C)-7a to 4-oxo(1
      (13)C1)decanoic acid ((13C)-8c) and a BVO of (13C)-8c to hexyl (1
      (13)C1)butanedioate ((13C)-9c) is reported. So far, BVO has been observed in
      bacteria and some fungi; the data presented indicate a BVO catalyzed by the yeast
      S. odorus in the course of endogenous lactone metabolism.

PMID- 17191891
TI  - Proposal of a new hydrogen-bonding form to maintain curdlan triple helix.
AB  - Curdlan and other beta-1,3-D-glucans form right-handed triple helices, and it has
      been believed that the intermolecular H-bond is present at the center of the
      helix to maintain the structure. In this H-bond model, three secondary OH groups
      form an inequilateral hexagonal shape perpendicular to the helix axis. This
      hexagonal form seems to be characteristic for beta-1,3-D-glucans and is widely
      accepted. We carried out MOPAC and ab initio calculations for the curdlan helix,
      and we propose a new intermolecular H-bonding model. In our model, the H-bonds
      are formed between the O2-atoms on different x-y planes along the curdlan helix,
      hence the H-bonds are not perpendicular to the helix axis. The new H-bonds are
      connected along the helix, traversing three curdlan chains to make a left-handed
      helix. Therefore, the H-bonding array leads to a reverse helix of the main chain.
      According to our MOPAC calculation, this model is more stable than the previous
      one. We believe that the continuous H-bonding array is stabilized by cooperative
      phenomena in the polymeric system.

PMID- 17191892
TI  - Microwave-induced enzyme-catalyzed chemoselective reduction of organic azides.
AB  - A lipase enzyme, suspended in organic media along with organic azides and
      irradiated under microwaves, enhances the reaction rate over thermal heating and
      affords the corresponding amines in high yields. The present biocatalytic method
      employing lipase is a significant development with remarkable regio- and
      chemoselectivity under microwave irradiation in organic media with excellent
      yields for the reduction of azide functionality.

PMID- 17191893
TI  - Synthesis of oligonucleotide-peptide conjugates carrying the c-myc peptide
      epitope as recognition system.
AB  - Oligonucleotide-peptide conjugates 1-3 were prepared by sequential addition of
      the appropriate Boc-protected amino acids, followed by nucleoside
      phosphoramidites in the same support. These molecules are designed to be used for
      triplex formation and for the directed assembly of nanomaterials. The structures
      of the desired oligonucleotide-peptide conjugates were confirmed by mass
      spectrometry on small oligonucleotide-peptide conjugates, by gel electrophoresis,
      and by hybridization with complementary oligonucleotides. Oligonucleotides
      carrying the c-myc peptide were specifically recognized by the anti-c-myc
      monoclonal antibody.

PMID- 17191894
TI  - Base-pairing systems related to TNA containing phosphoramidate linkages:
      synthesis of building blocks and pairing properties.
AB  - As part of a project that aims at screening TNA-related oligonucleotide systems
      in which threose backbone units may have some or all of their oxygen functions
      replaced by nitrogen, two TNA analogs containing (2'NH)- and (3'NH)
      phosphoramidate groups, respectively, in place of phosphodiester groups were
      synthesized. They show base-pairing properties that are very similar to those of
      TNA itself. We also synthesized 2',3'-diamino analogs of alpha-L-threofuranosyl
      mononucleosides, yet attempts to convert them to TNA analogs containing
      phosphodiamidate linker groups were not successful. Such 2',3'-diamino
      derivatives of threofuranosyl nucleosides may be of interest, however, as
      building blocks of TNA analogs that contain non-phosphorous linker groups.

PMID- 17191895
TI  - In the quest for a virtual pseudo receptor for sandalwood-like odorants. Part I:
      The empirical approach.
AB  - Based on similarities between naturally occurring (-)-(Z)-beta- or (+)-(Z)-alpha
      santalol ((-)- 1 or (+)-2, resp.) and the reversed (E)-configured synthetic
      derivatives from campholenal (7a), a simple model A was developed. Besides
      reconciliation of this stereochemical aspect, this initial model also tentatively
      explained the enantiodiscriminations as well as the large spectra of distances
      separating the OH function from the lipophilic quaternary center(s) reported for
      different classes of substrates. Evolution, modifications, and refinement of this
      imperfect model allied with the research for alternative possibilities are
      illustrated, along with a historical guideline, in the light of olfactively
      challenging synthetic seco-substructures as well as literature reports. Despite
      evolution of the inadequate model A and a plausible interpretation of the
      lipophilic part, the topological positions of the OH function and its vicinal
      alkyl substituent could nevertheless not be fully ascertained by this approach.
      This apparently inconclusive empirical concept prompted us to turn our attention
      towards a computerized methodology, which will constitute the second and third
      part of this study.

PMID- 17191896
TI  - 3-Methyl-3-sulfanylhexan-1-ol as a major descriptor for the human axilla-sweat
      odour profile.
AB  - This study sets out to redress the lack of knowledge in the area of volatile
      sulfur compounds (VSCs) in axillary sweat malodour. Sterile odourless underarm
      sweat (500 ml) was collected from 30 male volunteers after excessive sweating.
      Five strains of bacteria, Corynebacterium tuberculostearicum, Corynebacterium
      minutissimum, Staphylococcus epidermidis, Staphylococcus haemolyticus, and
      Bacillus licheniformis, were isolated and characterised for their ability to
      generate an authentic axillary odour from the sweat material collected. As
      expected, all of the five bacterial strains produced strong sweat odours.
      Surprisingly, after extensive olfactive evaluation, the strain of Staphylococcus
      haemolyticus produced the most sulfury sweat character. This strain was then
      chosen as the change agent for the 500 ml of odourless underarm sweat collected.
      After bacterial incubation, the 500-ml sample was further processed for GC
      olfactometry (GC-O), GC/MS analysis. GC-O of an extract free of organic acids
      provided three zones of interest. The first was chicken-sulfury, the second zone
      was onion-like, and the third zone was sweat, clary sage-like. From the third
      zone, a new impact molecule, (R)- or (S)-3-methyl-3-sulfanylhexan-1-ol, was
      isolated and identified by GC/MS, MD-GC, and GC AED (atomic emission detector).
      (S)-3-methyl-3-sulfanylhexan-1-ol was sniff-evaluated upon elution from a chiral
      GC column and was described as sweat and onion-like; its opposite enantiomer, (R)
      3-methyl-3-sulfanylhexan-1-ol, was described as fruity and grapefruit-like. The
      (S)-form was found to be the major enantiomer (75%).

PMID- 17191897
TI  - Progress towards development of a cholera subunit vaccine.
AB  - Cholera, an enteric disease that can reach pandemic proportions, remains a world
      wide problem that is positioned to increase in incidence as changes in global
      climate or armed conflict spawn the conditions that enhance transmission to
      humans and, thus, precipitate epidemic cholera. An effective subunit cholera
      vaccine that can provide protective immunity with one parenteral immunization
      would be a major advantage over the existing oral vaccines that can require two
      doses for optimal protection. The existing vaccines are clearly effective in some
      settings, but are less so in others, especially with respect to specific groups
      such as young (2-5 years) children. In our efforts to develop a cholera subunit
      vaccine, we focused on two Vibrio cholerae antigens, LPS (lipopolysaccharide) and
      TCP (toxin co-regulated pilus), that are known to induce protective antibodies in
      animal models and, in the case of anti-LPS antibodies, to be associated with
      clinical protection of V. cholerae exposed or vaccinated individuals. This review
      discusses the current cholera vaccines and compares the advantages of a cholera
      subunit vaccine to that of the whole cell vaccines. We discuss the possible
      subunit antigens and prospective targeted use of a subunit cholera vaccine.

PMID- 17191898
TI  - Identification of odoriferous sulfanylalkanols in human axilla secretions and
      their formation through cleavage of cysteine precursors by a C-S lyase isolated
      from axilla bacteria.
AB  - Human axillary odor is known to be formed upon the action of Corynebacteria sp.
      on per se odorless axilla secretions. Besides the known odoriferous acids, we
      report the occurrence in human axilla secretions of four odoriferous
      sulfanylalkanols, namely 3-sulfanylhexan-1-ol (3), 2-methyl-3-sulfanylbutan-1-ol
      (4), 3-sulfanylpentan-1-ol (5), and 3-methyl-3-sulfanylhexan-1-ol (6). These
      compounds have a pungent sweat/kitchen odor, also reminiscent of onions with some
      fruity connotations, and perception thresholds in the pg/l range. It was
      postulated that the odorless precursors for these compounds are cysteine
      conjugates. Bacterial isolates obtained from the human axilla and belonging to
      the Corynebacteria were, indeed, found to have the enzymatic capacity to release
      various thiols from cysteine conjugates. The metC gene, which is known to code
      for a cystathione-beta-lyase, was cloned from the axilla isolate Corynebacterium
      striatum Ax20 and heterologously expressed in E. coli. The pure recombinant
      enzyme cleaves various cysteine conjugates and has a similar substrate
      specificity as the cell homogenates of the wild-type. The recombinant enzyme was
      finally incubated with odorless axilla secretions and shown to release
      odoriferous thiols.

PMID- 17191899
TI  - Photo-induced processes in vitamin B6 compounds.
AB  - In this work, we applied multi-wavelength stopped-flow spectroscopy (MSFS) to
      study the chemical equilibria between tautomeric or hydrated forms of various
      vitamin B6 compounds and the Schiff base formed by epsilon-aminocaproic acid (= 6
      aminohexanoic acid) with pyridoxal 5'-phosphate at 25 degrees and variable pH.
      Since some of these compounds are photosensitive, we analyzed the possible
      occurrence of any secondary photo-induced processes under the conditions of
      irradiation in the MSFS equipment (continuous irradiation with light from a 75-W
      Xe lamp spanning the wavelength range of 200-700 nm). To determine the tautomeric
      composition of these compounds, the electronic absorption spectra were analyzed
      by means of log-normal curves. Continuous irradiation of pyridoxamine and
      pyridoxal 5'-phosphate over the wavelength range of 200-700 nm displaces the
      chemical equilibrium between the tautomeric or hydrated forms of these compounds.
      However, the Schiff base of epsilon-aminocaproic acid with pyridoxal 5'-phosphate
      is insensitive to the radiation used. The photo-induced processes detected in
      pyridoxamine and pyridoxal 5'-phosphate should be taken into account in examining
      vitamers by MSFS. In fact, these additional processes should be considered in
      studying the mechanism of action of vitamin B6-dependent enzymes by the MSFS
      technique, whenever some free vitamer may be present in solution.

PMID- 17191900
TI  - Thymosin beta 4 and its N-terminal tetrapeptide, AcSDKP, inhibit proliferation,
      and induce dysplastic, non-apoptotic nuclei and degranulation of mast cells.
AB  - Thymosin beta4 (Tbeta4), a 5 kDa polypeptide, is a member of the beta-thymosin
      family. It acts as the principal intracellular G-actin sequestering peptide and
      exhibits extracellular functions in angiogenesis and wound healing. The N
      terminus of Tbeta4 contains a bioactive tetrapeptide, acSDKP, a negative
      regulator of hematopoietic stem-cell proliferation. Here, we show that both
      peptides inhibit mast-cell proliferation over the concentration range of 10(-6)
      to 10(-17) M with the maximum effect of both at 10(-14) M. Both Tbeta4 and acSDKP
      caused dysplastic mast-cell nuclei that were confirmed by DAPI fluorescent
      staining. Flow-cytometric analysis of ploidy revealed that the dysplastic nuclei
      were not multinucleated, but fragmented nuclei in G2 growth arrest. We could
      further demonstrate that 10(-8) or 10(-14) M Tbeta4 or acSDKP induce mast-cell
      degranulation. A concentration of 10(-8) M Tbeta4 or acSDKP caused 57 or 89%
      degranulation, respectively. A number of tryptic fragments of Tbeta4 were assayed
      beside intact Tbeta4 and the tetrapeptide, and found to be inactive.

PMID- 17191901
TI  - Six new constituents from the roots of Erythrina variegata.
AB  - Three new isoflavonoids, eryvarins M-O (1-3), two new 2-arylbenzofurans,
      eryvarins P and Q (4 and 5), and a new 3-aryl-2,3-dihydrobenzofuran, eryvarin R
      (6), together with three known compounds, were isolated from the roots of
      Erythrina variegata. The structures of these compounds were established by
      spectroscopic analysis. Eryvarin R (6) is an unusual 3-aryl-2,3-dihydrobenzofuran
      derivative with a formyl (CHO) group. Eryvarin Q (5) showed potent antibacterial
      activity against methicillin-resistant Staphylococcus aureus.

PMID- 17191903
TI  - 9,10-Anthraquinones and other biologically active compounds from the genus Rubia.
AB  - The secondary metabolites isolated from Rubia species, their biological
      activities, and colouration properties have been reviewed. Over 150 chemical
      constituents belonging to different classes of bioactive compounds such as
      anthraquinones and their glycosides, naphthoquinones and glycosides, terpenes,
      bicyclic hexapeptides, iridoids, and carbohydrates are listed together with their
      source(s) and corresponding references.

PMID- 17191902
TI  - The world of beta- and gamma-peptides comprised of homologated proteinogenic
      amino acids and other components.
AB  - The origins of our nearly ten-year research program of chemical and biological
      investigations into peptides based on homologated proteinogenic amino acids are
      described. The road from the biopolymer poly[ethyl (R)-3-hydroxybutanoate] to the
      beta-peptides was primarily a step from organic synthesis methodology (the
      preparation of enantiomerically pure compounds (EPCs)) to supramolecular
      chemistry (higher-order structures maintained through non-covalent interactions).
      The performing of biochemical and biological tests on the beta- and gamma
      peptides, which differ from natural peptides/proteins by a single or two
      additional CH(2) groups per amino acid, then led into bioorganic chemistry and
      medicinal chemistry. The individual chapters of this review article begin with
      descriptions of work on beta-amino acids, beta-peptides, and polymers (Nylon-3)
      that dates back to the 1960s, even to the times of Emil Fischer, but did not
      yield insights into structures or biological properties. The numerous, often
      highly physiologically active, or even toxic, natural products containing beta-
      and gamma-amino acid moieties are then presented. Chapters on the preparation of
      homologated amino acids with proteinogenic side chains, their coupling to provide
      the corresponding peptides, both in solution (including thioligation) and on the
      solid phase, their isolation by preparative HPLC, and their characterization by
      mass spectrometry (HR-MS and MS sequencing) follow. After that, their structures,
      predominantly determined by NMR spectroscopy in methanolic solution, are
      described: helices, pleated sheets, and turns, together with stack-, crankshaft-,
      paddlewheel-, and staircase-like patterns. The presence of the additional C--C
      bonds in the backbones of the new peptides did not give rise to a chaotic
      increase in their secondary structures as many protein specialists might have
      expected: while there are indeed more structure types than are observed in the
      alpha-peptide realm - three different helices (10/12-, 12-, and 14-helix) if we
      include oligomers of trans-2-aminocyclopentanecarboxylic acid, for example - the
      structures are already observable with chains made up of only four components,
      and, having now undergone a learning process, we are able to construct them by
      design. The structures of the shorter beta-peptides can also be reliably
      determined by molecular-dynamics calculations (in solution; GROMOS program
      package). Unlike in the case of the natural helices, these compounds' folding
      into secondary structures is not cooperative. In beta- and gamma-peptides, it is
      possible to introduce heteroatom substituents (such as halogen or OH) onto the
      backbones or to incorporate heteroatoms (NH, O) directly into the chain, and,
      thanks to this, it has been possible to study effects unobservable in the world
      of the alpha-peptides. Tests with proteolytic enzymes of all types (from mammals,
      microorganisms, yeasts) and in vivo examination (mice, rats, insects, plants)
      showed beta- and gamma-peptides to be completely stable towards proteolysis and,
      as demonstrated for two beta-peptides, extraordinarily stable towards metabolism,
      even when bearing functionalized side chains (such as those of Thr, Tyr, Trp,
      Lys, or Arg). The beta-peptides so far examined also normally display no or only
      very weak cytotoxic, antiproliferative, antimicrobial, hemolytic, immunogenic, or
      inflammatory properties either in cell cultures or in vivo. Even biological
      degradation by microbial colonies of the types found in sewage-treatment plants
      or in soil is very slow. That there are indeed interactions of beta- and gamma
      peptides with biological systems, however, can be seen in the following findings:
      i) organ-specific distribution takes place after intravenous (i.v.)
      administration in rats, ii) transport through the intestines of rodents has been
      observed, iii) beta-peptides with positively charged side chains (Arg and Lys)
      settle on cell surfaces, are able to enter into mammalian cells (fibroplasts,
      keratinocytes, HeLa cells), and migrate into their cell nuclei (and nucleoli),
      and iv) in one case, it has already been established that a beta-peptide
      derivative can up- and down-regulate gene expression rates. Besides these less
      sharply definable interactions, it has also been possible to construct beta- and
      gamma-peptide agonists of naturally occurring peptide hormones, MHC-binding beta
      peptides, or amphipathic beta-peptide inhibitors of membrane-bound proteins in a
      controlled fashion. Examples include somatostatin mimics and the suppression of
      cholesterol transport through the intestinal brush-border membrane (by the SR-BI
      protein). The results so far obtained from investigations into peptides made up
      of homologues of the proteinogenic amino acids also represent a contribution to
      deepening of our knowledge of the natural peptides/proteins, while potential for
      biomedicinal application of this new class of substances has also been suggested.

PMID- 17191904
TI  - Synthesis, cytotoxicity, and apoptosis induction in human tumor cells by
      geiparvarin analogues.
AB  - A series of geiparvarin analogues modified on the unsaturated alkenyloxy bridge,
      where a H-atom replaced the 3'-Me group, were synthesized and evaluated against a
      panel of human tumor cell lines in vitro. These compounds demonstrated a stronger
      increase in growth inhibitory activity when compared to the parent compound
      geiparvarin (8). In particular, the activity increased even further in the series
      of demethylated compounds when a Me substituent in the coumarin moiety is
      introduced. On the contrary, the same modifications exerted on the parent
      compound led to an activity reduction. Interestingly, the new derivatives proved
      to be fully inhibitory to drug-resistant cell lines, thus suggesting that they
      are not subject to the pump-mediating efflux of antitumor drugs. On the basis of
      their cytotoxic profiles, the most-active compounds were selected for further
      biological evaluation. The extracellular acidification rate by the new
      geiparvarin analogues was measured with the Cytosensor microphysiometer. The new
      derivatives significantly increased the acidification rate during the 24-48 h of
      incubation in a concentration-dependent manner. Cell-cycle analysis, evaluated by
      flow cytometry, revealed a strong apoptotic induction by these compounds
      confirmed by DNA laddering and observation by electron microscopy. Interestingly,
      the apoptotic pathway did not appear to be mediated by the activation of caspase
      3.

PMID- 17191905
TI  - Electroreduction of oxygen by cytochrome C oxidase immobilized in electrode
      supported lipid bilayer membranes.
AB  - Cytochrome c oxidase is the terminal enzyme in mammalian respiration, and one of
      its main functions is to catalyze the reduction of oxygen under physiological
      conditions. Direct reduction of oxygen at electrodes requires application of
      substantial overpotentials. In this work, bovine cytochrome c oxidase has been
      immobilized in electrode-supported lipid bilayer membranes to investigate the
      electroreduction of oxygen under flow conditions. The effect that temperature,
      solution pH, and solution composition have on the reduction of oxygen by this
      novel enzyme-modified electrode is reported. Results indicate that the
      electroreduction of oxygen is most pronounced at low pH (6.4) and elevated
      temperature (38 degrees). At an applied potential of -350 mV vs. Ag/AgCl (1M
      KCl), a current density of ca. 7 microA/cm2 was obtained. The current responses
      obtained at these electrodes are stable over a period of ca. 10-14 days (10-15%
      decrease in response). The cytochrome c oxidase-modified electrodes described
      here could potentially be used for the direct electroreduction of oxygen to water
      in a biofuel cell.

PMID- 17191906
TI  - Cholinesterase-inhibiting withanolides from Ajuga bracteosa.
AB  - Three new withanolides, bracteosin A (= (22R)-5beta,6beta : 22,26-diepoxy
      4beta,28-dihydroxy-3beta-methoxyergost-24-ene-1,26-dione; 1), bracteosin B (=
      (22R)-5beta,6beta : 22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxy-1,26
      dioxoergost-24-en-19-oic acid; 2), and bracteosin C (= (22R)-22,26-epoxy
      4beta,6beta,27-trihydroxy-3beta-methoxyergost-24-ene-1,26-dione; 3), have been
      isolated from the whole plants of Ajuga bracteosa. Their structures were deduced
      by spectral analysis, including 1D- and 2D-NMR techniques. In addition,
      dihydroclerodin-1, clerodinin A, lupulin A, and dihydroajugapitin have also been
      isolated for the first time from this species. Compounds 1-3 exhibited evident
      inhibitory potential against cholinesterase enzymes in a concentration-dependent
      fashion.

PMID- 17191907
TI  - Nine new isoxuxuarine-type triterpene dimers from Maytenus chuchuhuasca.
AB  - Nine new isoxuxuarine-type triterpene dimers, named isoxuxuarines B alpha (1), B
      beta (2), 7,8-dihydro-B alpha (3), C alpha (4), C beta (5), 7,8-dihydro-C alpha
      (6), D alpha (7), D beta (8), and 7,8-dihydro-D alpha (9), were isolated from the
      South American medicinal plant 'xuxua' (Maytenus chuchuhuasca). The structures
      were elucidated on the basis of several spectroscopic analyses, including 2D-NMR
      experiments, MS spectra, and CD spectral studies. The isolations and structure
      elucidations of the new triterpene dimers are presented, and a rationale for the
      divergent formation of the regiochemical and stereochemical isomers of triterpene
      dimers is discussed.

PMID- 17191908
TI  - From earth's primitive atmosphere to chiral peptides--the origin of precursors
      for life.
AB  - To re-enact the long way to the origin of life with today's chemical methods,
      many steps have to be investigated in the light of a primordial scenario deduced
      from geochemical research. After the formation of our planet and its atmosphere,
      prebiotic chemical evolution started its course with the formation of the first
      building blocks for the formation of biomolecules. In the case of proteins, those
      building blocks were amino acids that had to be formed in the primitive
      atmosphere, and then had to react to peptides and proteins as the main pillar of
      first life. In this paper, we describe the processes in the primordial atmosphere
      according to contemporary geochemical knowledge leading to the synthesis of amino
      acids until the formation of homochiral peptides, and, thus, show a plausible
      pathway towards the origin of life.

PMID- 17191909
TI  - Bimetallic complexes of spiro-azacrown ligands as catalysts of phosphoester and
      phosphoric anhydride cleavage.
AB  - The ability of bimetallic homo- and heteronuclear complexes of two spiro-linked
      ligands, viz. a biazacrown (i.e., 2,6,10,14,18,22-hexaazaspiro[11.11]tricosane
      (1)) and an azacrown-crown ether (i.e., 14,17,20,23,26-pentaoxa-2,6,10-triaza
      spiro[11.15]heptacosane (2)), to promote the cleavage of the phosphoester linkage
      of dinucleoside 3',5'-phosphates and the phosphoric anhydride bridge of
      dinucleoside 5',5'-triphosphates was studied. In both reactions, the bimetallic
      homonuclear Cu2+ and Zn2+ complexes were better catalysts than their monometallic
      counterparts. The acceleration was two- to five-fold with the phosphoester
      cleavage and 3- to 20-fold with the phosphoric anhydride cleavage. Interestingly,
      the most-efficient catalyst of the phosphoester cleavage was the heterodinuclear
      Ni2+,Zn2+ complex of 1, the catalytic activity of which was up to 5- and 100-fold
      that of the homodinuclear Zn2+ and Ni2+ complexes, respectively. Moreover, this
      cooperative acceleration was observed to depend on the identity of the 5'-linked
      nucleoside: 3',5'-UpU and 3',5'-ApU were cleaved much faster than 3',5'-UpA, and
      no cooperative acceleration was observed with 3',5'-ApA. The reaction was second
      order in hydroxide ion concentration, suggesting that a double deprotonation took
      place on going from the initial to the transition state. Evidently, in addition
      to deprotonation of the attacking 2'-OH group, N(3)H of the 5'-linked uridine was
      displaced by one of the metal ions of the cleaving agent. With the phosphoric
      anhydride cleavage, no similar cooperativity of two different metal ions was
      observed, but the greatest rate-acceleration was achieved with the homodinuclear
      Cu2+ complexes.

PMID- 17191910
TI  - Antifeedant C20 diterpene alkaloids.
AB  - We have tested the insect antifeedant and toxic activity of 21 C20 diterpenoid
      alkaloids on Spodoptera littoralis and Leptinotarsa decemlineata. The antifeedant
      effects of the test compounds were structure- and species-dependent. The most
      active antifeedants to L. decemlineata and S. littoralis were the rearranged form
      of hetisine (20; EC50 = 1.7 microg/cm2) and 19-oxodihydroatisine (9; EC50 = 0.1
      microg/cm2), resp. Glandulosine (8) moderately affected orally injected S.
      littoralis larvae. A few compounds (13-oxocardiopetamine (4), 9, and atisinium
      chloride (13)) had cytotoxic effects to insect-derived Sf9 cells with varying
      degrees of selectivity with respect to mammalian CHO cells. Compounds 4 and 15,22
      O-diacetyl-19-oxodihydroatisine (10) increased Trypanosoma cruzi mortality. Our
      results support the plant protective role of C20 diterpenoid alkaloids and open a
      new field for parasite control strategies.

PMID- 17191911
TI  - Resolution of binary mixtures of rifamycin SV and rifampicin by UV/VIS
      spectroscopy and partial least-squares method (PLS).
AB  - A procedure is proposed for the joint determination of rifamycin SV and
      rifampicin by UV/VIS spectroscopy. A partial least-squares regression (PLS) was
      used for the resolution of the overlapping spectrophotometric signals from
      mixtures of the two drugs. The application of a genetic algorithm to select some
      of the predictor variables allows one to considerably reduce the number of
      experimental variables, as well as to improve the prediction capacity of the PLS
      model constructed with these selected potentials. Finally, the methods were
      applied to the determination of these drugs in biological samples.

PMID- 17191912
TI  - Sequence-specific binding of the Schizosaccharomyces pombe His1 protein to
      fission yeast telomeric DNA.
AB  - Sequence-specific protein-DNA interaction is critical for many important cellular
      processes such as transcription, DNA replication, and chromosome segregation.
      Identification of additional proteins that bind to DNA in a sequence-specific
      manner will contribute to the understanding of the mechanism of molecular
      recognition between protein and DNA. We found that the ATP phosphoribosyl
      transferase His1, which catalyzes the first step in histidine biosynthesis, is
      bound to both single- and double-stranded telomeric DNA. Competition experiments
      revealed that His1 is bound to a fission yeast telomeric DNA in a sequence
      specific manner. Previously identified sequence-specific telomere-binding
      proteins contain Myb domain. In contrast, Schizosaccharomyces pombe His1 does not
      contain Myb domain. These findings indicate that His1 has a novel DNA-recognition
      domain.

PMID- 17191914
TI  - Stereochemical studies on the making and unmaking of isopentenyl diphosphate in
      different biological systems.
AB  - To investigate the unknown stereochemical course of the reaction catalyzed by the
      type-II isomerase, which interconverts isopentenyl diphosphate (IPP) and
      dimethylallyl diphosphate (DMAPP), a sample of [1,2-(13)C2]-IPP
      stereospecifically labelled with 2H at C2 was prepared by incubating a D2O
      solution of (E)-4-hydroxy-3-methyl[1,2-(13)C2]but-2-enyl diphosphate with a
      recombinant IspH protein of Escherichia coli in the presence of NADH as a
      reducing agent and flavodoxin as well as flavodoxin reductase as auxiliary
      proteins. As monitored by 13C-NMR spectroscopy, treatment of the deuterated IPP
      with either type-I or type-II IPP isomerase resulted in the formation of DMAPP
      molecules retaining all the 2H label of the starting material. From the known
      stereochemical course of the type-I isomerase-catalyzed reaction, one has to
      conclude that the label introduced from D2O in the course of the IspH reaction
      resides specifically in the H(Si)-C2 position of IPP and that the two isomerases
      mobilize specifically the same H(Re)-C2 ligand of their common IPP substrate. The
      outcome of an additional experiment, in which unlabelled IPP was incubated in D2O
      with the type-II enzyme, demonstrates that the two isomerases also share the same
      preference in selecting for their reaction the (E)-methyl group of DMAPP.

PMID- 17191913
TI  - 13C-CPMAS and 1H-NMR study of the inclusion complexes of beta-cyclodextrin with
      carvacrol, thymol, and eugenol prepared in supercritical carbon dioxide.
AB  - Beta-cyclodextrin (beta-CD) inclusion complexes with carvacrol (1), thymol (2),
      and eugenol (3) (components of essential oils of vegetable origin) were prepared
      by the supercritical CO2 technique, and their structural characterization was
      achieved by means of 1H-NMR in aqueous solution and 13C-CPMAS NMR in the solid
      state. Evidence of the formation of the inclusion complexes for all the examined
      systems was obtained by 1H-NMR in solution, while 2D-ROESY-NMR experiments were
      used to investigate the geometry of inclusion. In addition, the dynamics of these
      inclusion complexes in the kHz timescale was investigated by analysis of the 1H
      and 13C spin-lattice relaxation times in the rotating frame.

PMID- 17191915
TI  - A novel carbazole derivative, BMVC: a potential antitumor agent and fluorescence
      marker of cancer cells.
AB  - We have investigated a novel compound, 3,6-bis[2-(1
      methylpyridinium)vinyl]carbazole diiodide (BMVC), for inhibiting telomerase
      activity and distinguishing human lung H1299 and oral Ca9-22 cancer cells from
      lung IMR90 and skin Detroit-551 normal fibroblast cells. The telomeric repeat
      amplification protocol (TRAP) assay shows that the concentration of BMVC that
      inhibits 50% of the telomerase activity (IC50) is ca. 0.05 microM. On the other
      hand, the cell-viability assay indicates that the cytotoxicity was less than 15%
      to the H1299 and Ca9-22 cancer cells, and almost negligible to the MRC-5 and
      Detroit-551 normal cells after incubation with 0.5 microM BMVC for 72 h. The low
      concentration of 0.05 microM of BMVC can inhibit telomerase activity but does not
      have general toxic effects to normal cells, implying that BMVC is a promising
      telomerase inhibitor. Moreover, wide-field fluorescence images of 0.1 microM BMVC
      treated cells show bright fluorescence spots in the nuclei of the most H1299 and
      Ca9-22 cancer cells. Interestingly, similar fluorescence spots are hardly
      observed in the nuclei of the IMR90 and Detroit-551 normal cells, implying that
      BMVC might be a useful marker to distinguish tumor cells and normal cells.

PMID- 17191916
TI  - Antimicrobial activity of hydrophobic xanthones from Cudrania cochinchinensis
      against Bacillus subtilis and methicillin-resistant Staphylococcus aureus.
AB  - Ten xanthones with one or two isoprenoid groups and a prenylated benzophenone
      isolated from roots of Cudrania cochinchinensis (Moraceae) were tested for their
      antimicrobial activities against Bacillus subtilis and methicillin-resistant
      Staphylococcus aureus (MRSA). Among these compounds, gerontoxanthone H exhibited
      considerable antibacterial activity against B. subtilis (MIC = 1.56 microg/ml).
      Four xanthones, gerontoxanthone I, toxyloxanthone C, cudraxanthone S, and 1,3,7
      trihydroxy-2-prenylxanthone, showed weak antibacterial activity against the
      bacterium (MICs = 3.13-6.25 microg/ml). These compounds also exhibited similar
      MIC values against methicillin-sensitive S. aureus, MRSAs, and Micrococcus
      luteus.

PMID- 17191917
TI  - Comparative metabolism of alpha- and beta-peptides in the insect Heliothis
      virescens and in plant cells of black Mexican sweet maize.
AB  - The tripeptide H-Val-Ala-Leu-OH and the N-Ac-tetrapeptide amide Ac-Thr-Lys-Trp
      Phe-NH2, and their beta-peptidic counterparts H-beta(3)hVal-beta(3)hAla
      beta(3)hLeu-OH and Ac-beta(3)hThr-(S)beta(2)hLys-beta(3)hTrp-beta(3)hPhe-NH2,
      respectively, have been injected into Heliothis virescens larvae and added to
      cell cultures of black mexican sweet maize. The body liquids of the larvae and
      the supernatant of the plant cell cultures were sampled 0, 2, 3, 6, 17, and/or 24
      h after application and analyzed by LC/MS. While the two alpha-peptides were
      degraded rapidly in these environments, the concentration of the beta-peptides
      was found to decrease very slowly. Thus, ca. 60% of the original amount of the
      beta-tetrapeptide was detected in the liquids of the insect after 24 h. The plant
      cells did not seem to make use of the beta-peptides at all, whereas, the alpha
      tripeptide completely disappeared from the supernatant after 3 h. Thus, we have
      demonstrated, for the first time, the high stability of beta-peptides against
      degradation and metabolism in an insect and a plant. Especially remarkable is the
      persistence of the beta-tetrapeptide with its functionalised and, thus,
      'metabolisable' side chains of Thr, Lys, Trp, and Phe in the insect larvae, which
      are known to have a high level of activity of oxidizing enzymes. The results
      described here match those of ADME investigations with radioactively labeled beta
      peptides in rats, where essentially complete stability has been observed, while
      environmental microorganisms have been found to biodegrade beta-peptides, albeit
      slowly. Possible implications of these findings for biomedical and pest-control
      applications are proposed.

PMID- 17191918
TI  - Pyrimidine as constituent of natural biologically active compounds.
AB  - This review describes the various manifestations of the pyrimidine system
      (alkylated, glycosylated, benzo-annelated.). These comprise pyrimidine
      nucleosides as well as alkaloids and antibiotics--some of them have been
      discovered and isolated from natural sources already long time ago, others have
      been reported very recently. A short overview on pyrimidine syntheses (prebiotic
      synthesis, biosynthesis, and metabolism) is given. The biological activities of
      most of the pyrimidine analogs are briefly described, and, in some cases,
      syntheses are formulated.

PMID- 17191919
TI  - Biosynthesis of new indigoid inhibitors of protein kinases using recombinant
      cytochrome P450 2A6.
AB  - Glycogen synthase kinase-3 (GSK-3) is a potential drug target for a number of
      human diseases. Some indigoids have been found to be potent inhibitors of GSK-3,
      and individual compounds with better activity, specificity, and solubility are
      desired. In this work, a new disubstituted indigoid generation system was
      developed with a tryptophanase-deficient Escherichia coli strain as a host to
      express the human cytochrome P450 2A6 mutant L240C/N297Q, which catalyzes the
      oxidation of indole to isatin and indoxyl, which in turn react to generate
      indigoids. Forty-five substituted 1H-indoles from commercial sources were used as
      substrates in the system, and indigoid mixtures were tested as potential
      inhibitors of GSK-3. After preliminary screening, cell extracts with high
      inhibitory activity towards GSK-3alpha/beta were fractionated, and the IC50
      values of twelve individual indigoids were measured for GSK-3alpha/beta as well
      as the protein kinases CDK1/cyclinB and CDK5/p25. Several indigoids, including an
      indigo, showed stronger inhibition than found in previous work. The most potent
      towards GSK-3alpha/beta, dimethyl indirubin 5,5'-dicarboxylate (IC50 of 51 nM),
      was modified by chemical reactions. One product, indirubin 5,5'-dicarboxylic acid
      5-methyl ester, inhibited GSK-3alpha/beta with an IC50 of 14 nM and selectivity
      nearly 40-fold over CDK1 and CDK5. Indirubin-5-5'-dicarbonitrile was also
      modified to the corresponding 3'-oxime, which had low specificity but showed very
      high inhibition of all three kinases with IC50 values of 5, 13, and 10 nM towards
      GSK-3alpha/beta, CDK1, and CDK5, respectively. Thus, this system has the
      potential to generate new indigoids with therapeutic potential.

PMID- 17191920
TI  - Exploratory studies to investigate a linked prebiotic origin of RNA and coded
      peptides. 4th Communication. Further observations concerning pyrimidine
      nucleoside synthesis by stepwise nucleobase assembly.
AB  - As part of an ongoing investigation into a possible linked origin of RNA and
      coded peptides, we have (further) investigated the potentially prebiotic
      synthesis of pyrimidine ribonucleosides (ribonucleotides), by stepwise nucleobase
      assembly on sugar (sugar phosphate) scaffolds. In this paper, we complete our
      description of this assembly process on aldopentose scaffolds. Treatment of D
      ribose (14) and D-xylose (20) with cyanamide smoothly produces the furanosylamino
      oxazolines 15 and 21, respectively (Schemes 1 and 3). Similar treatment of D
      lyxose (26) also produces the furanosylamino-oxazoline 29, but as a minor
      component of an equilibrating mixture in which the pyranosylamino-oxazoline 28
      predominates (Scheme 4). Treatment of the various amino-oxazolines with
      cyanoacetylene gives furanosylcytidines 16, 25, and 31, and the
      lyxopyranosylcytidine 30 (Schemes 1-4). Minor by-products of the cyanoacetylene
      reaction include imino lactone 17, acetals 19, 22, and 24, and cyanovinyl adducts
      22 and 23 resulting from initial addition of nucleoside OH groups to the terminal
      acetylenic C-atom of cyanoacetylene (Schemes 2-4).

PMID- 17191921
TI  - Ion-specific aggregation of gold-DNA nanoparticles using the dG quartet hairpin
      5'-d(G4T4G4).
AB  - Ion-selective self-assembly of Au nanoparticles is described. The Oxytricha
      telomere DNA hairpin 5'-d(G4T4G4) immobilized on 13-nm Au nanoparticles forms a
      supramolecular assembly via dG-quartets, as determined by the color change and by
      scanning electron microscopy (SEM). The aggregation is ion-dependent and
      selective for Na+ ions. K+ is less efficient, while Li+ and Cs+ do not drive the
      aggregation. This work is the first effort to explore the use of secondary
      structures of DNA (quadruplexes) for producing self-assemblies of Au
      nanoparticles. It can be utilized to generate novel devices and materials,
      potentially useful for sensing and other applications in medicinal or engineering
      science.

PMID- 17191922
TI  - Metal ion complexes of macrocyclic polyamines enhance both the phosphate
      hydrolysis and imidazole ring opening of RNA 5'-cap structure.
AB  - The cleavage of P1-(7-methylguanosyl-5') P3-(guanosyl-5') triphosphate, a RNA 5'
      cap model, by 2-hydroxyethyl- (6a-6c) and 2-aminoethyl- (7a-7c) substituted
      macrocycles in the presence and absence of Zn2+ and Cu2+ ions has been studied at
      pH 7.2 and 60 degrees. In the presence of the metal ions, hydrolysis of the
      phosphate group is enhanced. The mono- and dinuclear Zn2+ complexes promote
      solely the phosphate hydrolysis, whereas the corresponding Cu2+ complexes
      accelerate both the phosphate hydrolysis and the imidazole ring opening of the 7
      methylguanine base. In the absence of the metal ions, the macrocycles mainly
      promote breakdown of the 7-methylguanine base, most probably by enhancing the
      nucleophilic attack of hydroxide ion on the C(8)-atom by shielding the repulsive
      negative charge on the phosphate moiety. The 2-hydroxyethyl and 2-aminoethyl side
      arms exhibit a two- to three-fold rate acceleration. Opening of the imidazole
      ring eventually results in cleavage of the triphosphate bridge.

PMID- 17191923
TI  - Isolation and lipoxygenase-inhibition studies of phenolic constituents from
      Ehretia obtusifolia.
AB  - The phenolic compounds methyl 2-O-feruloyl-1a-O-vanillactate (1), caffeic
      anhydride (2), and trans 4-hydroxycyclohexyl-2-O-p-coumaroyl beta-D
      glucopyranoside (3) have been isolated from the AcOEt-soluble fraction of Ehretia
      obtusifolia, along with methyl rosmarinate (4) and rosmarinic acid (5), which are
      reported for the first time from this species. Their structures were determined
      by means of 1D- and 2D-NMR techniques. Compounds 1-5 inhibited lipoxygenase in a
      concentration-dependent manner, with Ki values ranging from 0.85-57.6 microM.
      Compounds 1, 2, 4, and 5 showed noncompetitive inhibition, whereas 3 was found to
      be an uncompetitive inhibitor of lipoxygenase.

PMID- 17191924
TI  - Identification of diverse microbial metabolites as potent inhibitors of HIV-1 Tat
      transactivation.
AB  - HIV-1 Tat is one of six regulatory proteins that are required for viral
      replication and is an attractive target for the development of new anti-HIV
      agents. Screening of microbial extracts using a whole cell Tat-dependent
      transactivation assay, which guided the separation of the active broths, led to
      the identification of five structurally diverse classes (M(R) range 232-1126) of
      natural products. These include i) three sesquiterpenoids, namely, sporogen-AO1,
      petasol, and 6-dehydropetasol, ii) two resorcylic 14-membered lactones, namely
      monorden and monocillin IV, iii) a ten-membered lactone, iv) a quinoline and
      quinoxiline bicyclic octadepsipeptides, namely echinomycin and UK-63598, and v) a
      cyclic heptapeptide, ternatin. These compounds displayed varying degrees of
      potencies with IC50 values ranging from 0.0002 to 100 microM. The most active
      compound was the quinoxiline bicyclic octadepsipeptides, UK-63598, which
      inhibited Tat-dependent transactivation with an IC50 value of 0.2 nM and
      exhibited a 100-fold therapeutic window with respect to toxicity. In a single
      cycle antiviral assay, UK-6358 inhibited viral replication with an IC50 value of
      0.5 nM; however, it appeared to be equally toxic at that concentration.
      Monocillin IV was significantly less active (Tat transactivation inhibitory IC50
      of 5 microM) but was not toxic at 100 microM in an equivalent cytotoxicity assay.
      The compound exhibited antiviral activity with an IC50 value of 6.2 microM in the
      single-cycle antiviral assay and a sixfold therapeutic window. Details of the
      isolation, fermentation, and biological activities of these structurally diverse
      natural products are described.

PMID- 17191926
TI  - Isoprenylated xanthones and flavonoids from Cudrania tricuspidata.
AB  - Further phytochemical investigation on the roots of Cudrania tricuspidata
      afforded a new isoprenylated xanthone, cudratricusxanthone I (1), two new
      isoprenylated flavanones, cudraflavanones C and D (2 and 3, resp.), and seven
      known compounds, 1,7-dihydroxy-3,6-dimethoxyxanthone (4), macluraxanthone C (5),
      cudraxanthones E, K, and L (6, 7, and 8, resp.), cudraflavanone A (9), and
      cudraflavone C (10). Their structures were identified by spectroscopic methods.
      Cudratricusxanthone H (12), macluraxanthone B (13), two xanthones previously
      isolated from this plant, and 5, showed significant inhibitory effects on four
      kinds of human digestive apparatus tumor cell lines (HCT-116, SMMC-7721, SGC
      7901, and BGC-823) with IC50 values of 2.70-12.66 microM.

PMID- 17191925
TI  - A new destruxin as inhibitor of vacuolar-type H+-ATPase of Saccharomyces
      cerevisiae.
AB  - In the course of our screening efforts to discover small molecules as selective
      inhibitors of vacuolar-type H+-ATPase of Saccharomyces cerevisiae, we have
      identified eight active destruxins, 1-8, from the fungus Metarhizium anisopliae.
      The structures were elucidated by extensive 1D- and 2D-NMR spectroscopy, and MS
      spectrometry. One of these compounds, 8, a regioisomer of chlorohydrin destruxin
      E (7), is a new destruxin.

PMID- 17191927
TI  - Antifungal constituents from the Chinese moss Homalia trichomanoides.
AB  - Bioautographic assay on TLC plates was adopted to guide the fractionation of the
      Et2O extract of Homalia trichomanoides (Hedw.) B. S. G., which led to the
      isolation of the novel p-terphenyl derivative trichomanin (= 4,4''-dihydroxy
      1,1':4',1''-terphenyl-2',3',5',6'-tetrayl tetrakis(phenylacetate); 1), together
      with five known compounds: 3alpha-methoxyserrat-14-en-21beta-ol (2), 3beta
      methoxyserrat-14-en-21beta-ol (3), 3beta-methoxyserrat-14-en-21-one (4),
      atranorin (5), and methyl 2,4-dihydroxy-3,6-dimethylbenzoate (6). Their
      structures were determined on the basis of spectral data (1D- and 2D-NMR, MS), X
      ray crystallographic analysis, and chemical transformation. Compounds 3, 5, and 6
      exhibited antifungal activity against Candida albicans, with minimum inhibitory
      doses (MID) of 2.0, 2.0, and 0.6 microg, respectively.

PMID- 17191928
TI  - Flared gases and other pollutants associated with air quality in industrial areas
      of Nigeria: an overview.
AB  - Nigeria, like any other developing nation, is faced with the twin problem of
      development without destruction. Industrialization, though an important component
      of development, has had a large share in the despoilation of air quality in the
      country by the release of high amounts of pollutants into the atmosphere.
      Petroleum hydrocarbons from refineries, flared gases, dusts, and fumes of metal
      smelting and cement works, odorous gases of chemical and allied industries,
      carbon monoxide and oxides of sulfur and nitrogen of internal combustion engines,
      the charred particulates and sulfur dioxide emissions of the steel industries
      etc., all constitute pollutants or co-pollutants of the Nigerian atmosphere. This
      review article gives an insight into the phenomenal concentrations of some of
      these pollutants in the Nigerian atmosphere, which point to their unsafe levels
      and concomitant health risks. It is against this background that there should be
      continuous but sound monitoring exercise of the Nigerian environment, devoid of
      the peculiar mix of politics and science, in order to properly audit the quality
      of air, especially in areas of heavy industrial pollution. Such checks and
      balances would provide empirical data to assess the various trade-offs of
      atmospheric pollution in industrial areas of the country such as the Niger Delta
      region where oil and gas are produced. There should also be enforcement, thereof,
      of all existing and/or revised standards or regulations such as the compliance
      limits of the Department of Petroleum Resources (DPR) or the erstwhile Federal
      Environmental Protection Agency (FEPA).

PMID- 17191929
TI  - Alpha1- and alpha2-adrenoreceptor antagonist profiles of 1- and 2-[omega-(4
      arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles.
AB  - A series of pharmacologically interesting 1- and 2-[omega-(4-arylpiperazin-1
      yl)alkyl]-1,2,3-benzotriazoles, compounds 1-27, were synthesized (Scheme) and
      subjected to various biological studies to identify structure-activity
      relationships (SAR). The new compounds were found to exhibit good non-selective
      binding affinity towards the alpha1-adrenoreceptor (Table 1). In several cases,
      high functional antagonism was observed towards the alpha1A-, alpha1B-, and
      alpha1D-adrenoreceptor subtypes (Table 2). The selectivity for these three
      subtypes was comparable with or superior to that displayed by the standard drug
      prazosin. The most-common selectivity rank order was alpha1D > alpha1B > alpha1A,
      followed by alpha1B > alpha1D > alpha1A. In functional experiments, antagonism
      towards the alpha2-adrenoreceptor was generally low; however, a few compounds
      were endowed with significant antagonist properties (pA2 values of up to 7.87).

PMID- 17191930
TI  - Anti-tumor-initiating effects of monascin, an azaphilonoid pigment from the
      extract of Monascus pilosus fermented rice (red-mold rice).
AB  - Monascin (1) constitutes one of the azaphilonoid pigments in the extracts of
      Monascus pilosus-fermented rice (red-mold rice). Compound 1 was evaluated for its
      anti-tumor-initiating activity via oral administration on the two-stage
      carcinogenesis of mouse skin tumor induced by peroxynitrite (ONOO-; PN) or by
      ultraviolet light B (UVB) as an initiator and 12-O-tetradecanoylphorbol-13
      acetate (TPA) as a promoter. Compound 1 exhibited marked inhibitory activity on
      both PN- and UVB-induced mouse skin carcinogenesis tests. These findings suggest
      that compound 1 may be valuable as potential cancer chemopreventive agent in
      chemical and environmental carcinogenesis.

PMID- 17191932
TI  - Two new taxoids from Taxus chinensis.
AB  - Two new taxoids, 2,20-O-diacetyltaxumairol N (1) and 14beta-hydroxy-10-deacetyl-2
      O-debenzoylbacatin III (2), were isolated from the needles and stems of Taxus
      chinensis. Their structures were determined on the basis of extensive 1D- and 2D
      NMR-spectral analysis. Compound 1 showed weak cytotoxicity activity against T-24
      (IC50 = 34 microg/ml) and QGY-7701 (IC50 = 22 microg/ml) cancer lines. Compound 2
      showed no obvious cytotoxicity activity against T-24 (IC50 > 100 microg/ml) and
      QGY-7701 (IC50 > 100 microg/ml) cancer lines.

PMID- 17191931
TI  - A new xanthone glycoside and antioxidant constituents from the rhizomes of
      Swertia speciosa.
AB  - From the rhizomes of Swertia speciosa, a traditional medicinal plant from the
      Himalayan region of Uttaranchal (North India), a new constituent, 6-hydroxy-3,5
      dimethoxy-1-[(6-O-beta-D-xylopyranosyl-beta-D-glucopyranosyl)oxy]-9H-xanthen-9
      one (8), was isolated, together with nine known compounds. Their structures were
      elucidated on the basis of chemical, physical, and spectroscopic evidence. Both
      the acetone and MeOH extracts, as well as the known constituents ursolic acid (5)
      and 1,5,8-trihydroxy-3-methoxy-9H-xanthen-9-one (6) exhibited potent antioxidant
      activities in different biological assays (Table 2).

PMID- 17191933
TI  - Synthesis and anti-amoebic activity of gold(I), ruthenium(II), and copper(II)
      complexes of metronidazole.
AB  - A series of Au, Ru, and Cu complexes of metronidazole (= [1-(2-hydroxyethyl)-2
      methyl-5-nitro-1H-imidazole; 1) were prepared as highly potent anti-amoebic
      drugs. The complexes [Au(PPh3)(1)]PF6 (2), [Ru(1)2(Cl)2(H2O)2] (3), and
      [Cu(1)2(mu-Cl)(H2O)]2Cl2 (4) were readily synthesized from [Au(PPh3)Cl], RuCl3 x
      3 H2O, and CuCl2 x 2 H2O, respectively. All complexes were thoroughly
      characterized by IR, UV/VIS, 1H-NMR, FAB-MS, elemental and thermogravimetric
      analyses, and, in the case of 4, also by X-ray crystallography (Fig. 1). All
      complexes were evaluated in vitro as growth inhibitors of Entamoeba histolytica
      (HM1:IMSS strain). Their IC50 values were in the range of 0.10-0.51 microM (Table
      2), which makes these drugs, especially the Cu(II) complex 4, considerably more
      potent than uncomplexed metronidazole (1; IC50 = 1.81 microM), the current
      standard drug for the worldwide treatment of amoebiasis.

PMID- 17191934
TI  - Synthesis of demethylxanthohumol, a new potent apoptosis-inducing agent from
      hops.
AB  - Starting from commercially available phloracetophenone (= 1-(2,4,6
      trihydroxyphenyl)ethanone), we synthesized demethylxanthohumol (4), a derivative
      of xanthohumol, devoid of 6'-O-methyl group. Both are prenylchalcones derived
      from hops (Humulus lupulus). The synthesis was accomplished by an aldol
      condensation between MOM-protected acetophenone 2 and MOM-protected benzaldehyde
      3. The resulting demethylxanthohumol (4) displayed antiproliferative properties.
      Demethylxanthohumol (4) induced also apoptosis via the mitochondrial pathway in
      BJAB cells (Burkitt lymphoma cell line) and in primary lymphoblasts of childhood
      acute lymphoblastic leukemia (ALL).

PMID- 17191935
TI  - Novel peptide-based copper(II) complexes for total hydrolytic cleavage of DNA.
AB  - Stable Cu(II) complexes with histamine- and histidine-containing dipeptides
      histidylserine and histidylphenylalanine have been developed. Their interaction
      in solution has been investigated, and the stability of their complexes was
      determined. The nature of binding in these complexes has been explained with the
      help of potentiometric pH titrations and 1H-NMR spectroscopy. The geometry of
      these complexes has been established by electronic spectra. The DNA-binding and 
      cleavage abilities of these Cu(II) complexes have been probed by the absorption,
      thermal denaturation, fluorescence, and electrophoresis experiments. The results
      suggest that these peptide-based Cu(II) complexes effectively bind and
      efficiently cleave DNA under mild biological conditions. Since Cu(II) complexes
      are known to play an important role in phosphodiester bond cleavages, these
      results assume importance.

PMID- 17191936
TI  - Cytotoxic activity and constituents of the volatile oil from the roots of
      Patrinia scabra Bunge.
AB  - The volatile oil from the roots of Patrinia scabra Bunge was isolated by steam
      distillation, and separated into four major fractions (Fr. A-D) by means of
      column chromatography. A total of 39 compounds (1-39) were identified by GC/MS
      analysis, and evaluated for their in vitro cytotoxic activities against human
      ovarian carcinoma cells (HO-8910) and human hepatoma cells (Bel-7402) (Table 1).
      Fr. A showed the strongest inhibitory effect on HO-8910 (IC50 = 21 microg/ml) and
      Bel-7402 cells (16 mcirog/ml), whereas Fr. B was the least active (>100
      microg/ml). By comparison of the constituents of the four fractions, we assume
      that the cytotoxicity of the volatile oil of P. scabra is mainly due to the
      lignans and azulenes, rather than to caryophyllene oxide I (18). Our results
      suggest that the volatile oil of P. scabra possesses potent and tumor-specific
      cytotoxicity, and could serve as a possible candidate for future cancer
      chemotherapy.

PMID- 17191937
TI  - Bioactive deoxypreussomerins and dimeric naphthoquinones from Diospyros
      ehretioides fruits: deoxypreussomerins may not be plant metabolites but may be
      from fungal epiphytes or endophytes.
AB  - Deoxypreussomerin derivatives, palmarumycins JC1 (1) and JC2 (2), and two dimeric
      naphthoquinones, isodiospyrin (3) and its new derivative isodiospyrol A (4), were
      isolated from dried fruits of Diospyros ehretioides. Structures of the isolated
      compounds were elucidated by spectroscopic analyses. Palmarumycins were not found
      in the extract of freshly collected fruits; however, they were present in dried
      fruit extract. The absence of palmarumycins in fresh fruits of D. ehretioides,
      together with the chemotaxonomic point of view, we proposed that palmarumycins
      JC1 (1) and JC2 (2) are more likely to be fungal metabolites, i.e., endophytes or
      epiphytes. The isolation of palmarumycins 1 and 2 from dried D. ehretioides
      fruits could be reproducible; both plant samples collected in the years 2002 and
      2004 provided the same result, and, therefore, symbiont fungal strains should be
      specific to the plant host, D. ehretioides, and they can grow on the fruits
      during drying the sample. Palmarumycin JC1 (1) did not exhibit antimalarial,
      antifungal, antimycobacterial, and cytotoxic activities. Palmarumycin JC2 (2)
      exhibited antimalarial (IC50 4.5 microg/ml), antifungal (IC50 12.5 microg/ml),
      antimycobacterial (MIC 6.25 microg/ml), and cytotoxic (IC50 11.0 microg/ml for
      NCI-H187 cell line) activities. In our bioassay systems, isodiospyrin (3) did not
      exhibit antimycobacterial, antifungal, antimalarial, and cytotoxic activities.
      Isodiospyrol A (4) exhibited antimalarial (IC50 2.7 microg/ml) and
      antimycobacterial (MIC 50 microg/ml) activities, but was inactive towards Candida
      albicans. Compound 4 also exhibited cytotoxicity against BC cells (IC50 12.3
      microg/ml), but not towards KB and Vero cell lines.

PMID- 17191938
TI  - Post-oil-spill fires at Ugbomro (Niger Delta): a new vista in soil-pollution
      studies.
AB  - Reconnaissance of the post-oil-spill, fire-scourged site at Ugbomro, in the Niger
      Delta, was contingent upon the loud public outcry and galvanizing hue that ensued
      the widespread conflagration. Sampling was carried out by the grid technique, and
      fire-scourged soils and their unaffected controls were analyzed. Contrary to the
      'celebrated' opinion of some that the fires improvised bush fallowing for
      cropping, the site had witnessed severe impoverishment as evidenced by the
      hitherto neglected insidious impact of such infernos on soil macronutrients.
      Alterations in physico-chemical properties (pH, conductivity, etc.) provided
      adequate bases for this conclusion, and offered broad explanations for the
      paucity of macronutrients in affected soils. For instance, a pH range of 3.1-3.8
      hindered N2 fixation and other metabolic activities that enhance mineralization.
      Elaeis guineensis in a density of 3 stands/m2 at the control site was the only
      tree-form not charred beyond recognition.Against future fires, it is important to
      strengthen contingencies for more-expedient clean-up responses to oil spills to
      severe possibilities of in situ conflagrations. Nutrient supplementations,
      revegetation, and site surveillance should disengage the 'unsighted fingers' of
      sabotage. A careful husbandry of these measures might re-establish nutrient
      stability, and forestall future re-occurrence of such effacing incidents.

PMID- 17191939
TI  - Antimalarial constituents from Nauclea orientalis (L.) L.
AB  - Bioassay-guided fractionation of the antimalarial-active CHCl3 extract of the
      dried stem of Nauclea orientalis (L.) L. (Rubiaceae) has resulted in the
      isolation of two novel tetrahydro-beta-carboline monoterpene alkaloid glucosides,
      naucleaorine (= (16alpha,17beta)-3,14:15,20-tetradehydro-16-ethenyl-17-(beta-D
      glucopyranosyloxy)-19alpha-methoxyoxayohimban-21-one; 1) and
      epimethoxynaucleaorine (2), as well as the known compounds, strictosidine lactam
      (= (15beta,16alpha,17beta)-19,20-didehydro-16-ethenyl-17-(beta-D
      glucopyranosyloxy)oxayohimban-21-one; 3), 3,4,5-trimethoxyphenol (4), 3alpha
      hydroxyurs-12-en-28-oic acid methyl ester (5), 3alpha,23-dihydroxyurs-12-en-28
      oic acid (6), 3alpha,19alpha,23-trihydroxyurs-12-en-28-oic acid methyl ester (7),
      and oleanolic acid (8). Compounds 1, 2, 6, and 8 showed moderate in vitro
      activities against Plasmodium falciparum. Their structures and configurations
      were elucidated by spectroscopic methods including 1D- and 2D-NMR analyses.

PMID- 17191940
TI  - Pentamidine is an antiparasitic and apoptotic drug that selectively modifies
      ubiquitin.
AB  - We have determined the cytotoxic properties of pentamidine isethionate (2)
      towards the promastigotes of the protozoan parasite Leishmania infantum. The
      leishmanicidal activity of 2 was 60 times higher after 72 h of incubation than
      that of cisplatin (4). The pentamidine salt 2 induced a higher amount of
      programmed cell death (PCD) than cisplatin, which is associated with inhibition
      of DNA synthesis and cell-cycle arrest in the G2/M phase. Circular dichroism (CD)
      data indicate that binding of 2 to calf-thymus DNA (CT-DNA) induces
      conformational changes in the DNA double helix, consistent with a B-->A
      transition. Moreover, the interaction of 2 with ubiquitin led to a 6% increase in
      the beta-sheet content of the protein as observed by CD spectroscopy.
      Fluorescence-spectroscopy studies agreed with the CD data, showing that the
      pentamidine portion of 2 induces a significant decrease in the fluorescence of
      the Ub residues Phe4 and Phe45 located on the beta-cluster of the molecule, but
      not of Tyr59 on the alpha-cluster. These data indicate that pentamidine
      specifically modifies the beta-cluster, i.e., the 'basic face' of ubiquitin. Our
      results suggest that the biochemical mechanism of action of pentamidine may be a
      consequence of its dual binding to DNA and proteins.

PMID- 17191941
TI  - Microbial transformations of gelomulide G: a member of the rare class of
      diterpene lactones.
AB  - Microbial transformation of gelomulide G (3beta,6beta-diacetoxy-8beta,14beta
      epoxyabiet-13(15)-en-16,12-olide, 1) was carried out. Incubation of 1 with
      Aspergillus niger afforded two new metabolites, 3beta,6beta-diacetoxy
      8beta,14beta-dihydroxyabiet-13(15)-en-16,12-olide (2) and 3beta,6beta-diacetoxy
      14beta-hydroxyabieta-8(9),13(15)-dien-16,12-olide (3). While Cunninghamella
      elegans afforded the 14-epimer of 2, i.e., 3beta,6beta-diacetoxy-8beta,14alpha
      dihydroxyabiet-13(15)-en-16,12-olide (4), along with 3beta-acetoxy-6beta-hydroxy
      8beta,14beta-epoxyabiet-13(15)-en-16,12-olide (5). The structures of the
      transformed products 2-5 were deduced to be new on the basis of MS and NMR data.

PMID- 17191943
TI  - Musings on ADME predictions and structure-activity relations.
AB  - The first part of the paper examines Structure-Activity Relations (SARs) and
      their components from a very general point of view. The various types of
      interpretation emerging from statistically valid relations will be examined,
      namely causal (mechanistic), contextual (empirical), fortuitous, and tautological
      correlations. Implications for ADME predictions will be seen when discussing the
      diversity of interactions between active compounds (e.g., drugs) and biological
      systems. The second part of the paper is more specific and presents the concept
      of molecular-property space, an all but neglected concept in SARs. Recent results
      from Molecular Dynamics (MD) simulations and Molecular Interaction Fields (MIF)
      computations of acetylcholine will be used to illustrate not only the well-known
      conformational space of this molecule, but also its property space as exemplified
      by its lipophilicity space. It will be seen that a molecule as small as
      acetylcholine is able to span a relatively broad property space. Most
      significantly in an ADME perspective, the molecule is able, within the limits of
      its property space, to adapt to the medium. This is equivalent to saying that the
      medium constrains the molecule to resemble it as much as feasible.

PMID- 17191944
TI  - The prediction of ADMET properties using structure information representations.
AB  - The electrotopological state and molecular connectivity indices are defined as a
      system for molecular-structure description, using the term Structure-Information
      Representation. This system is built on the depiction of a molecule as a network
      composed of atoms of varying valence electron counts that constitute the valence
      state, bonded in discrete patterns constituting an electrotopological state. The
      system is employed in the structure-activity analysis of two sets of ADMET data.
      Models are created relating hepatotoxicity and human metabolic stability. The
      validity of these models makes them useful for activity prediction.

PMID- 17191945
TI  - Application of 3D-QSAR in the rational design of receptor ligands and enzyme
      inhibitors.
AB  - Quantitative structure-activity relationships (QSARs) are frequently employed in
      medicinal chemistry projects, both to rationalize structure-activity
      relationships (SAR) for known series of compounds and to help in the design of
      innovative structures endowed with desired pharmacological actions. As a
      difference from the so-called structure-based drug design tools, they do not
      require the knowledge of the biological target structure, but are based on the
      comparison of drug structural features, thus being defined ligand-based drug
      design tools. In the 3D-QSAR approach, structural descriptors are calculated from
      molecular models of the ligands, as interaction fields within a three-dimensional
      (3D) lattice of points surrounding the ligand structure. These descriptors are
      collected in a large X matrix, which is submitted to multivariate analysis to
      look for correlations with biological activity. Like for other QSARs, the
      reliability and usefulness of the correlation models depends on the validity of
      the assumptions and on the quality of the data. A careful selection of compounds
      and pharmacological data can improve the application of 3D-QSAR analysis in drug
      design. Some examples of the application of CoMFA and CoMSIA approaches to the
      SAR study and design of receptor or enzyme ligands is described, pointing the
      attention to the fields of melatonin receptor ligands and FAAH inhibitors.

PMID- 17191947
TI  - Development and application of physiologically based pharmacokinetic-modeling
      tools to support drug discovery.
AB  - Physiologically based pharmacokinetic (PBPK) modeling integrates physicochemical
      (PC) and in vitro pharmacokinetic (PK) data using a mechanistic framework of
      principal ADME (absorption, distribution, metabolism, and excretion) processes
      into a physiologically based whole-body model. Absorption, distribution, and
      clearance are modeled by combining compound-specific PC and PK properties with
      physiological processes. Thereby, isolated in vitro data can be upgraded by means
      of predicting full concentration-time profiles prior to animal experiments. The
      integrative process of PBPK modeling leads to a better understanding of the
      specific ADME processes driving the PK behavior in vivo, and has the power to
      rationally select experiments for a more focussed PK project support. This
      article presents a generic disposition model based on tissue-composition-based
      distribution and directly scaled hepatic clearance. This model can be used in
      drug discovery to identify the critical PK issues of compound classes and to
      rationally guide the optimization path of the compounds toward a viable
      development candidate. Starting with a generic PBPK model, which is empirically
      based on the most common PK processes, the model will be gradually tailored to
      the specifics of drug candidates as more and more experimental data become
      available. This will lead to a growing understanding of the 'drug in the making',
      allowing a range of predictions to be made for various purposes and conditions.
      The stage is set for a wide penetration of PK modeling and simulations to form an
      intrinsic part of a project starting from lead discovery, to lead optimization
      and candidate selection, to preclinical profiling and clinical trials.

PMID- 17191946
TI  - Rational design and development of radiation-sensitizing histone deacetylase
      inhibitors.
AB  - Histone deacetylases (HDACs) offer potentially attractive molecular targets for
      sensitizing cancers to treatment with radiation therapy. By affecting patterns of
      gene expression, differentiation, apoptosis, and enhanced responses to
      therapeutic agents may be induced in cancer cells. Here, we review the drug
      characteristics underlying design and screening of HDAC inhibitors with a focus
      on radiation-sensitizing properties. Radiation-sensitizing capacities have been
      observed in three model systems, squamous carcinoma of head and neck origin (SQ
      20B), prostate adenocarcinoma (PC-3), and breast adenocarcinoma (MCF7). Cell-type
      specificities in radiation-sensitizing properties have been observed. Mechanisms
      underlying specificity are under investigation.

PMID- 17191948
TI  - Analysis and understanding of high-dimensionality data by means of multivariate
      data analysis.
AB  - Multivariate analysis such as principal-components analysis (PCA) and partial
      least-squares-discriminant analysis (PLS-DA) have been applied to peptidomics
      data from clinical urine samples subjected to LC/MS analysis. We show that it is
      possible to use these methods to get information from a complex set of clinical
      data. The aim of the work is to use this information as a first step in the
      further search for clinical biomarker data. It is possible to identify peptide
      biomarker fingerprints related to disease diagnosis and progression. Further, we
      review clinical proteomics and pharmacogenomics data analyzed with the same
      multivariate approach.

PMID- 17191949
TI  - A signature-based method to distinguish time-of-flight secondary-ion mass spectra
      from biological samples.
AB  - Time-Of-Flight Mass Spectrometry (TOF-SIMS) was used to determine elemental and
      biomolecular ions from isolated protein samples. We identified a set of 23 mass
      to-charge ratio (m/z) peaks that represent signatures for distinguishing
      biological samples. The 23 peaks were identified by Singular Value Decomposition
      (SVD) and Canonical Analysis (CA) to find the underlying structure in the complex
      mass-spectra data sets. From this modified data, SVD was used to identify sets of
      m/z peaks, and we used these patterns from the TOF-SIMS data to predict the
      biological source from which individual mass spectra were generated. The
      signatures were validated using an additional data set different from the initial
      training set used to identify the signatures. We present a simple method to
      identify multiple variables required for sample classification based on mass
      spectra that avoids overfit. This is important in a variety of studies using mass
      spectrometry, including the ability to identify proteins in complex mixtures and
      for the identification of new biomarkers.

PMID- 17191950
TI  - Molecular simulation study of the influence of small molecules on the dynamic and
      structural properties of phospholipid bilayers.
AB  - Molecular simulations were performed for phospholipid bilayers as model cell
      membranes to understand their dynamic and structural properties, in particular
      how those are affected in the presence of the cell-preservation agents trehalose
      and DMSO. Simulations covered a large range of temperatures and concentrations of
      trehalose and DMSO. A number of properties were examined, including the area per
      head group, lipid-tail order parameter, density profile, conformation, and
      binding of trehalose. Our results indicate that trehalose specifically interacts
      with the phospholipid bilayer by binding to the polar head groups (H-bonds). This
      binding serves as a bridge between the lipids and prevents their aggregation. The
      hydrophilic nature of trehalose also makes it a water substitute when binding to
      the phospholipids. At high trehalose concentrations, trehalose forms a glassy
      matrix and preserves the bilayer structure by 'freezing' it in its natured state,
      as the core of the bilayer is found to remain fluid. Simulations with DMSO
      revealed that DMSO can penetrate and freely diffuse through the bilayer, which is
      attributed to its unique characteristic of interacting favorably with both
      hydrophilic and hydrophobic domains.

PMID- 17191951
TI  - Yucca: an efficient algorithm for small-molecule docking.
AB  - In this paper, we present a new algorithm, which is based on an efficient
      heuristic for local search, for rigid protein-small-molecule docking. We tested
      our algorithm, called Yucca, on the recent 100-complex benchmark, using the
      conformer generator OMEGA to generate a set of low-energy conformers. The results
      showed that Yucca is competitive both in terms of algorithm efficiency and
      docking accuracy.

PMID- 17191952
TI  - Application of molecular modeling to analysis of inhibition of kinesin motor
      proteins of the BimC subfamily by monastrol and related compounds.
AB  - Application of molecular modeling approaches has potential to contribute to
      rational drug design. These approaches may be especially useful when attempting
      to elucidate the structural features associated with novel drug targets. In this
      study, molecular docking and molecular dynamics were applied to studies of
      inhibition of the human motor protein denoted HsEg5 and other homologues in the
      BimC subfamily. These proteins are essential for mitosis, so compounds that
      inhibit their activity may have potential as anticancer therapeutics. The
      discovery of a small-molecule cell-permeable inhibitor, monastrol, has stimulated
      research in this area. Interestingly, monastrol is reported to inhibit the human
      and Xenopus forms of Eg5, but not those from Drosophila and Aspergillus. In this
      study, homology modeling was used to generate models of the Xenopus, Drosophila,
      and Aspergillus homologues, using the crystal structure of the human protein in
      complex with monastrol as a template. A series of known inhibitors was docked
      into each of the homologues, and the differences in binding energies were
      consistent with reported experimental data. Molecular dynamics revealed
      significant changes in the structure of the Aspergillus homologue that may
      contribute to its relative insensitivity to monastrol and related compounds.

PMID- 17191953
TI  - Chemical and structural diversity in cyclooxygenase protein active sites.
AB  - A major pharmaceutical problem is designing diverse and selective lead compounds.
      The human genome sequence provides opportunities to discover compounds that are
      protein selective if we can develop methods to identify specificity determinants
      from sequence alone. We have analyzed sequence and structural diversity of sheep
      COX-1 and mouse COX-2 proteins by Active Site Profiling (ASP). Eleven residues
      that should serve as specificity determinants between COX-1 and COX-2 were
      identified; however, the literature suggests that only one has been utilized in
      structure-based discovery. ASP was used to create a position-specific scoring
      matrix, which was used to identify possible cross-reacting proteins from the
      human sequences. This method proved selective for cyclooxygenases, comparing well
      with results using BLAST. The methods identify a probable misannotation of a
      cyclooxygenase in which there is high sequence similarity scores using BLAST, but
      ASP shows it does not contain the residues necessary for cyclooxygenase function.
      ASP Analysis of human COX proteins suggests that some specificity determinants
      that distinguish COX-1 and COX-2 proteins are similar between sheep COX-1/mouse
      COX-2 and human COX-1/COX2; however, residue identities at those positions are
      not necessarily conserved. Our results lay groundwork for development of family
      specific pattern recognition methods to selectively match compounds with
      proteins.

PMID- 17191954
TI  - A three-dimensional model of intercellular calcium signaling in epithelial cells.
AB  - We have developed a fully three-dimensional (3D) model of calcium signaling in
      epithelial cells based on a set of reaction diffusion equations that are solved
      on a large-scale finite-element code in three dimensions. We have explicitly
      included the cellular compartments including the cell nucleus, cytoplasm, and gap
      junctions. The model allows for buffering of free Ca2+, calcium-induced calcium
      release, and the explicit inclusion of mobile buffers. To make quantitative
      comparisons to experimental results, we used fluorescence microscopy images of
      cells to generate an accurate mesh describing cell morphology. We found that Ca2+
      wave propagation through the tissue is a function of both initial conditions used
      to start the wave and various geometrical parameters that affect propagation such
      as gap junction density and distribution, and the presence of nuclei. The
      exogenous dyes used in experimental imaging also affect wave propagation.

PMID- 17191955
TI  - Identification of novel neuroprotective agents using pharmacophore modeling.
AB  - In addition to its endocrine function, for which it was named, thyrotropin
      releasing hormone (TRH) has substantial neuroprotective actions as well as other
      physiological effects. We have developed a number of modified TRH analogues as
      well as cyclic dipeptides structurally related to a major metabolic product of
      TRH, which have enhanced neuroprotective activity but none of the other major
      physiological effects of TRH. The extensive structure-activity data developed
      with these compounds were used to develop a pharmacophore model. Subsequently, a
      web-based pharmacophore searching program was used to query several large three
      dimensional databases. Of the 219 compounds identified whose structures met the
      pharmacophore model, 15 were chosen for study in a classical model of neuronal
      cell death in vitro; five of these, 2-6, showed neuroprotective activity. Thus,
      pharmacophore modeling developed from neuroprotective small peptides can be used
      to identify novel lead compounds as neuroprotective agents.

PMID- 17191956
TI  - Methodology for multi-site ligand-protein docking identification developed for
      the optimization of spirostenol inhibition of beta-amyloid-induced neurotoxicity.
AB  - Spirostenol steroids have been found to inhibit beta-amyloid-induced
      neurotoxicity. We have evaluated in parallel experimental and molecular-modeling
      studies the relative effectiveness of 17 (22R)-hydroxycholesterol derivatives in
      binding to the target peptide. Our results support the previous evidence that
      beta-amyloid offers multiple docking sites for these steroids. Molecular modeling
      allowed for the correlation of spirostenol candidate structural differences with
      a choice of proposed active sites. A multi-site identification technique based on
      a Site-Identifier Matrix (SIM) was developed that clearly showed the uniqueness
      of our lead (maximum neurotoxicity inhibition) candidate SP233, with a nearly
      equal docking affinity for two sites.

PMID- 17191957
TI  - Rationalizing the solution properties of zwitterions by means of computational
      chemistry.
AB  - This short review describes our computational studies of carnitine,
      acetylcarnitines, and betaines over the past two decades. Interspersed among the
      three computational studies--a molecular mechanics study of the conformer
      population of carnitine and acetylcarnitine, an AM1 study of the energetics of
      hydrolysis of acetylcarnitine, and an HF 6-31G* study of the solvation energies
      and structures of a homologous series of betaines--are brief overviews of our
      research in designing and testing new therapeutic agents for non-insulin
      dependent diabetes and for protection against sexually transmitted diseases. The
      three studies also show how computational chemistry has evolved during this time
      to enable an evaluation of the structure and energetics of zwitterions in aqueous
      solution.

PMID- 17191958
TI  - New natural taxane diterpenoids from Taxus species since 1999.

PMID- 17191960
TI  - New racemosol derivatives as potent cyclooxygenase (COX) inhibitors.
AB  - Racemosol (1) and 10-O-demethylracemosol (2), natural products from Bauhinia
      malabarica Roxb., exhibit potent in vitro anti-inflammatory activities against
      cyclooxygenase-1 and -2 (COX-1 and -2) enzymes. To investigate the structure
      activity relationship (SAR) of these molecules, we prepared and fully
      characterized 17 derivatives by functionalizing one, two, or all three OH
      group(s) of 2 (Scheme). Both the size and polarity of the substituents as well as
      the substitution pattern in compounds 3a-q were found to be critical for anti
      inflammatory activity. The orientation of the drugs and their mode of binding
      were studied by molecular docking based on the known 3D structure of the complex
      between COX-2 and the drug SC-558. Whereas the monoacetoxy derivative 3h
      exhibited an equally potent inhibitory activity towards both COX-1 and -2 (Table
      1), its diacetoxy congener 3i was slightly more selective toward COX-2. In vivo
      anti-inflammatory tests showed that 3i and 2 are slightly more active than the
      reference compound phenylbutazone (Table 2).

PMID- 17191959
TI  - N-linked glycosylated beta-peptides are resistant to degradation by glycoamidase
      A.
AB  - Beta-peptides are resistant to degradation by a variety of proteolytic enzymes
      that rapidly degrade natural alpha-peptides. This is one of many characteristics
      that make beta-peptides an attractive class of compounds for drug discovery
      efforts. To further understand the molecular recognition properties of beta
      peptides and the ability of enzymes to degrade them, we have synthesized a series
      of N-linked glycosylated beta- and alpha-peptides, and tested their stability
      towards a glycosidase. We found that glyco-beta-peptides that contain N
      acetylglucosamine (1) or N,N-diacetylchitobiose (2) are completely stable to
      degradation by glycoamidase A. In comparison, the glyco-alpha-peptides 3 and 4
      containing N-acetylglucosamine or N,N-diacetylchitobiose are degraded. Inhibition
      experiments using increasing concentrations of a glyco-beta-peptide fail to
      inhibit degradation of the corresponding glyco-alpha-peptide, even when the glyco
      beta-peptide is at a 128-fold higher concentration than the glyco-alpha-peptide.
      Evidently, the glyco-beta-peptides have a much weaker affinity for the active
      site of the glycosidase than the corresponding glyco-alpha-peptide. These and the
      results with proteolytic enzymes suggest that the additional CH(2) group
      introduced into the alpha-amino acid residues causes beta-peptides not to be
      recognized by hydrolytic enzymes. The results described herein suggest the
      potential of beta-peptides that are functionalized with carbohydrates for
      biological and biomedical investigations, without having to be concerned about
      the carbohydrate being removed.

PMID- 17191961
TI  - Photocytotoxic pheophorbide-related compounds from Aglaonema simplex.
AB  - In our screening program for new photosensitizers from the Malaysian
      biodiversity, we found five pheophorbide-related compounds from the leaves and
      stems of Aglaonema simplex. Detailed spectroscopic analyses showed that compounds
      1-3 and 5 are pheophorbide and hydroxy pheophorbide derivatives of chlorophyll a
      and b. Compound 4, identified as 15(1)-hydroxypurpurin-7-lactone ethyl methyl
      diester, was isolated for the first time from the Araceae family. An MTT-based
      short-term survival assay showed that all five compounds exhibit moderate-to
      strong photocytotoxic activities towards human leukemia (HL60) and two oral
      squamous carcinoma cell lines (HSC-2 and HSC-3). Compounds 4 and 5 showed the
      strongest photocytotoxicities, with IC(50) values of 0.30-0.41 muM (Table 2).
      Compounds 1-3 with Et chains at C(17(3)) were less photocytotoxic than the parent
      pheophorbide a (5).

PMID- 17191962
TI  - Combinatorial synthesis and antibacterial evaluation of an indexed chalcone
      library.
AB  - A 120-membered chalcone library has been designed and prepared from six
      differently substituted acetophenones (A1-A6) and 20 benzaldehydes (B1-B20). The
      library was subjected to biological studies targeted against six bacterial
      strains. For the identification of the most-active member(s) of the library, the
      so-called indexed or positional-scanning method was applied. Six out of 26 sub
      libraries, i.e., AL1-AL6, were synthesized by keeping the acetophenone moiety A
      fixed and using equimolar quantities of the 20 different benzaldehydes. The
      remaining 20 sub-libraries BL1-BL20 were prepared by keeping the benzaldehyde B
      component fixed and varying the six acetophenones (Table 1). The bactericidal
      activities of the resulting sub-libraries were tested and used as indices to the
      rows or columns of a two-dimensional matrix. Finally, parallel synthesis of 24
      specific members with the highest-expected antibacterial activities, present in
      two sub-libraries, was carried out. These chalcones were screened again, and the
      results were exploited for establishing the structure-activity relationship (SAR)
      and the identification of the lead compound, which turned out to be 1,3-bis(2
      hydroxyphenyl)prop-2-en-1-one (A2B2) in terms of activity towards Staphylococcus
      aureus and Bacillus subtilis (Tables 5-7).

PMID- 17191963
TI  - Cytotoxic ent-kaurane diterpenoids from Isodon eriocalyx.
AB  - Five new ent-kaurane diterpenoids, epi-maoecrystal N (1), eriocalyxin G (2),
      maoecrystal W (3), maoecrystal X (4), and maoecrystal Y (5), along with 22 known
      ones, were isolated from Isodon eriocalyx (Dunn.) Hara., and their structures
      were determined by spectroscopic methods. All diterpenoids, except for 3 and 13,
      were evaluated for inhibition of the K562, T-24, Me180, QGY-7701, and BIU87 cell
      lines (Table 2).

PMID- 17191964
TI  - New resveratrol tetramers from the stem bark of Upuna borneensis.
AB  - Five new resveratrol (=5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol)
      tetramers, upunaphenols H-J (1-3) and trans-(4) and cis-upunaphenol K (5), were
      isolated from the stem of Upuna borneensis (Dipterocarpaceae). Their structures
      were elucidated on the basis of 1D- and 2D-NMR as well as FAB-MS data. Compounds
      1-3 bear a rare biphenyl bond in their frameworks. Compounds 1 and 2 have an
      unprecedented nonacyclic fused ring system, and compounds 2 and 3 have
      symmetrical structures.

PMID- 17191965
TI  - Yeast polysaccharide affects fusaric acid content in maize root rot.
AB  - Protective action of sulfoethyl glucan (SEG), a derivative of the cell wall
      glucan prepared from the baker's yeast Saccharomyces cerevisiae, was investigated
      in the maize seedlings infected by a plant pathogen Fusarium verticillioides
      (Sacc.). Several markers were assayed with the SEG addition and in the control
      experiments. Two evaluations were performed on the 7th and the 14th days.
      Addition of SEG led to the increased productivity parameters of the infected
      plants and maintained them at the level of non-infected plants during the 14 days
      of experiment. After seven days of cultivation, concentration of fusaric acid (=5
      butylpyridine-2-carboxylic acid; FA) decreased in all infected plants cultivated
      in the presence of SEG when compared to that detected in the infected plants
      grown in the absence of SEG. After 14 days of cultivation, polysaccharide
      addition resulted in the reduction of FA concentration almost to 75% in
      comparison to the infected plants grown without polysaccharide addition. In the
      experiment, when exogenous FA was added to the growth medium, its concentration
      decreased up to 60% in the presence of SEG. Thus, it is feasible to assume that
      SEG binds and adsorbs FA, and, in this way, reduces its content and exerts
      protective action in plants against its toxic effect.

PMID- 17191966
TI  - The molecular retention mechanism in reversed-phase liquid chromatography of meso
      ionic compounds by quantitative structure-retention relationships (QSRR).
AB  - Absorption, distribution, metabolism, and excretion (ADME) properties are of
      invaluable importance to a bioactive compound. Permeation process is one of the
      most widely studied by many different techniques. Among them, reversed-phase
      liquid chromatography (RP-LC) is proving to be of great interest, in which
      retention time can provide some insights on the hydrophobic interaction behavior.
      A series of antiprotozoal meso-ionic 1,3,4-thiadiazolium-3-aminides were studied
      in order to obtain the retention-time data through two different organic
      modifiers using a commercially available Supelcosil ABZ(+) Plus column.
      MeOH/buffer mobile phase provided the best results in assessing the
      hydrophobicity of these compounds as compared to MeCN. Quantitative Structure
      Retention Relationships (QSRR) models were built to identify the physicochemical
      properties that govern the process by using PLS analysis. VolSurf descriptors
      extracted from water (H(2)O), hydrophobic (DRY), amide N-atom (N(1)) and carbonyl
      O-atom (O) probes showed that the retention is positively correlated to the
      molecules size and shape, hydrophobic pattern, and dispersion forces. Hydrogen
      bonding depicts the solvent force considering the donor and acceptor differences
      between MeOH and MeCN organic modifiers.

PMID- 17191967
TI  - Three new immunomodulating C21-steroidal glycosides from the stems of Stephanotis
      mucronata.
AB  - Three new C(21)-steroidal glycosides stemucronatosides H, I, and J (1-3, resp.)
      were isolated from the stems of Stephanotis mucronata, together with three known
      compounds sinomarinoside A (4), sinomarinoside E (5), and stephanoside H (6).
      These isolated compounds were tested for their immunological activities in vitro
      against concanavalin-A(Con A)- and lipopolysaccharide(LPS)-induced proliferation
      of mice splenocytes. Compounds 3, 4, and 6 showed immunosuppressive activities in
      a dose-dependent manner, while compounds 1, 2, and 5 possessed immunoenhancing
      activities.

PMID- 17191970
TI  - Strategies and tools for structure determination of natural products using modern
      methods of NMR spectroscopy.

PMID- 17191971
TI  - Enhancing the methyl-donor activity of methylcobalamin by covalent attachment of
      DNA.
AB  - The preparation of a covalent DNA conjugate of vitamin B12 by means of
      heterogeneous solid-phase synthesis is reported. The cyano-corrinoid made
      available, dipotassium Co(beta)-cyanocobalamin-(3''-->2'),(3''-->5')-bis-2''
      deoxythymidyl-3''-ate (K(2)-4), was cleanly methylated at the Co center by
      electrosynthetic means. Aqueous solutions of the resulting organometallic DNA-B12
      conjugate K(2)-5 exhibited spectroscopic properties indicative of significant
      weakening of the axial (Co-N) bond, together with a 25-times higher basicity
      relative to Co(beta)-methylcobalamin (2). Methyl-transfer equilibria of pH
      neutral aqueous solutions of K(2)-5 and cob(I)alamin (K-7) on one side, and of
      cob(I)alamin-(3''-->2'),(3''-->5')-bis-2''-deoxythymidyl-3''-ate (K(3)-8) and
      methylcobalamin (2) on the other, were studied at room temperature (Scheme 3).
      The NMR-derived data provided an equilibrium constant of ca. 0.3. Activation of
      K(2)-5 for abstraction of its Co-bound Me group by a nucleophile (such as
      cob(I)alamin) was, thus, indicated.

PMID- 17191972
TI  - Activity and stability of hammerhead ribozymes containing 2'-C-methyluridine: a
      new RNA mimic.
AB  - We propose 2'-C-methylnucleotides as a new class of 2'-modified RNA mimics. These
      analogues are expected to provide 2'-OH groups capable of reproducing the
      interactions observed in natural RNA and, due to the presence of the Me group, to
      possess increased stability towards nucleases. In this work, we investigate the
      catalytic activity and nuclease resistance of hammerhead ribozymes carrying 2'-C
      methyluridines in positions 4 and 7 of the catalytic core. We describe the in
      vitro activity of these chimeric molecules and their stability in cell lysate,
      fetal calf serum, and cell culture medium. The data show that, when only position
      4 is modified, activity decreases twofold; while, when both 4 and 7 positions are
      substituted, a sevenfold drop in activity is observed. Regarding biological
      stability, the main increase of the half-life time is observed when position 7 is
      modified. These results suggest that 2'-C-methylnucleotides may be useful in the
      design of chemically synthesized RNA mimics with biological activity.

PMID- 17191973
TI  - Synthesis and cytotoxic evaluation of certain 4-(phenylamino)furo[2,3-b]quinoline
      and 2-(furan-2-yl)-4-(phenylamino)quinoline derivatives.
AB  - Certain 4-(phenylamino)furo[2,3-b]quinoline and 2-(furan-2-yl)-4
      (phenylamino)quinoline derivatives were synthesized and evaluated in vitro
      against the full panel of NCIs 60 cancer cell lines. The preliminary results
      indicated these tricyclic 4-(phenylamino)furo[2,3-b]quinolines were more
      cytotoxic than their corresponding 2-(furan-2-yl)-4-(phenylamino)quinoline
      isomers. For the 4-(phenylamino)furo[2,3-b]quinolines, compounds 2a and 3d are
      two of the most potent with a mean GI50 value of 0.025 microM in each case.
      Inactivity of 2b and 2c (positional isomers of 2a) indicated that both electronic
      environment, and the distance between intercalating pharmacophore and H-bond
      donating MeO group are important. For the 2-(furan-2-yl)-4-(phenylamino)quinoline
      isomers, compound 12 (a mean GI50 of 4.36 microM), which bears a para-COMe
      substituent, is more active than its meta-substituted counterpart 13 (10.5
      microM). However, the electron-donating MeO substituent is preferred at the meta
      position, and the cytotoxicity for the meta-substituted derivatives decreased in
      the order: MeO derivative 14b (3.05 microM) > oxime 16 (6.85 microM) > ketone 13
      (10.5 microM) > methyl oxime 18 (20.6 microM).

PMID- 17191974
TI  - Formic acid catalysed rearrangement of 5beta-methyldihydrothevinols (= 3,6
      dimethoxy-5,17-dimethyl-4,5-epoxy-6,14-ethanomorphinan-7-methanols): synthesis of
      new doubly bridged morphinan derivatives.
AB  - We recently showed that substitution of a 5beta-methyl group allows the isolation
      of 14-alkenyldihydrocodeinones from the action of hot formic acid on certain
      dihydrothevinols. It has now been shown that, in those dihydrothevinols which are
      converted to stable side chain olefins by such treatment, introduction of a 5beta
      methyl group results in the formation of new doubly bridged morphinan derivatives
      in addition to the dihydrocodeinones or olefins. The new morphinans have low
      affinities for opioid receptors.

PMID- 17191975
TI  - Bioactive constituents from Turkish Pimpinella species.
AB  - A new 'phenylpropanoid', 4-(3-methyloxiran-2-yl)phenyl 2-methylbutanoate (1), a
      new trinorsesquiterpene, 4-(6-methylbicyclo[4.1.0]hept-2-en-7-yl)butan-2-one (2),
      and eight known compounds (3-10) were isolated from the essential oils of several
      Pimpinella species growing in Turkey. The structures of the new compounds were
      determined by 1D- and 2D-NMR analyses. The absolute configuration of 1 was
      established via comparison of its optical rotation with that of
      'epoxypseudoisoeugenyl 2-methylbutyrate' (11), the absolute configuration of
      which was determined by chemical degradation and an appropriate Mosher ester
      formation. Direct bioautography revealed antifungal activity of 1 and 11 against
      Colletotrichum acutatum, C. fragariae, and C. gloesporioides. Subsequent
      evaluation of antifungal compounds in a 96-well microtiter assay showed that
      compounds 1 and 11 produced the most-significant growth inhibition in Phomopsis
      spp., Colletotrichum spp., and Botrytis cinerea. Compounds 1 and 6 displayed
      antimicrobial activities against Mycobacterium intracellulare, with IC50 values
      of 2.78 and 1.29 microM, respectively.

PMID- 17191976
TI  - Modeling biochemical networks: a cellular-automata approach.
AB  - The potential of the cellular-automata (CA) method for modeling biological
      networks is demonstrated for the mitogen-activated protein kinase (MAPK)
      signaling cascade. The models derived reproduced the high signal amplification
      through the cascade and the deviation of the cascade enzymes from the Michaelis
      Menten kinetics, evidencing cooperativity effects. The patterns of pathway change
      upon varying substrate concentrations and enzyme efficiencies were identified and
      used to show the ways for controlling pathway processes. Guidance in the
      selection of enzyme inhibition targets with minimum side effects is one outcome
      of the study.

PMID- 17191977
TI  - New gemacranolides from Eupatorium hualienense.
AB  - Phytochemical investigation of Eupatorium hualienense (C. H. Ou, S. W. Chung, C.
      I. Peng) has resulted in the isolation of the new sesquiterpene lactones 1-5,
      named eupahualins A-E, along with the known heliangolide eupasimplicin B (6). The
      structures of the isolated compounds were established through detailed spectral
      analyses, especially by means of 2D-NMR techniques. Compounds 1-4 and 6 showed
      significant activities against cell lines of human chronic myelogenous leukemia
      (K562) and human bone cancer (U2OS).

PMID- 17191978
TI  - Synthesis, and cytotoxic and antiplatelet activities of oxime- and methyloxime
      containing flavone, isoflavone, and xanthone derivatives.
AB  - A series of oxime- and methyloxime-containing flavone, isoflavone, and xanthone
      derivatives (1-12) were synthesized (Scheme) and evaluated for their cytotoxic
      (Table 1) and antiplatelet activities (Table 2). The in vitro anticancer assay
      indicated that the cytotoxicity of structurally related compounds decreases in
      the order isoflavones (7a-7c) > flavones (8a-8c) > xanthones (9a-9c), electron
      releasing substituents (R) on the Ph ring being favorable (mean GI50 values of
      2.84, 12.3, and 20.9 microM for 7c, 8c, and 9c, resp.). The inhibition of
      platelet aggregation induced by arachidonic acid (AA) similarly decreased from
      the isoflavone 1 (IC50 = 2.97 microM) to the flavone 2 (7.70 microM) to the
      xanthone 3 (inactive). Thereby, compound 1 seems to be a promising lead, since it
      was not only the most-potent aggregation inhibitor (IC50 = 2.97 microM), but was
      also found to be noncytotoxic at a concentration of 100 microM.

PMID- 17191979
TI  - Antiplasmodial activity of naphthoquinones related to lapachol and beta
      lapachone.
AB  - The in vitro antiplasmodial activity of 26 naphthoquinone derivatives related to
      the natural lapachol (1) and beta-lapachone (2) was tested. Ten of these
      derivatives are reported for the first time. The evaluation was performed on
      cultures of F32 strain of Plasmodium falciparum, and some derivatives displayed
      attractive in vitro activities (IC50 < 10 microM). Based on these results, some
      structure-activity relationships have been determined.

PMID- 17191980
TI  - Synthesis and triplex-forming properties of cyclic oligonucleotides with (G,A)
      antiparallel strands.
AB  - Cyclic oligonucleotides carrying an oligopurine Watson-Crick sequence linked to
      the corresponding (G,A)- and (G,T)-antiparallel strands were prepared by
      nonenzymatic template-assisted cyclization of phosphorylated precursors.
      Cyclization was attempted using 3'-phosphate and 5'-phosphate linear precursors
      with carbodiimide or BrCN activation. The best results were obtained with the 5'
      phosphorylated precursors and carbodiimide activation. Cyclic oligonucleotides
      bind polypyrimidine target sequence by formation of antiparallel triplexes. We
      have used UV and circular dichroism (CD) spectroscopy to analyze triplexes formed
      by cyclic oligonucleotides carrying G and A in the reverse-Hoogsteen strand. The
      relative stability of the triplexes formed by cyclic and linear oligonucleotides
      with a common polypyrimidine target was determined by melting experiments. The
      most-stable triplexes were formed by the cyclic oligonucleotide, followed by the
      unphosphorylated and phosphorylated oligonucleotide precursors, and, finally, the
      corresponding hairpin. Although the differences in binding affinity between
      cyclic oligonucleotides and their corresponding linear precursors are small, the
      use of cyclic oligonucleotides offers a clear advantage over conventional duplex
      recognition.

PMID- 17191981
TI  - Antitumor-promoting effects of new sesquiterpenes from Crossopetalum tonduzii.
AB  - Seven new sesquiterpenes (1-7) with a 'dihydro-beta-agarofuran' (= 5,11-epoxy
      5beta,10alpha-eudesmane) skeleton were isolated from Crossopetalum tonduzii.
      Their structures were elucidated spectroscopically, especially by means of homo-
      and heteronuclear NMR correlation (COSY, ROESY, HSQC, and HMBC). The absolute
      configurations of the new compounds were determined by circular dichroism (CD)
      studies and by chemical correlations via the derivatives 8-11. The new compounds
      showed moderate antitumor-promoting effects with respect to the activation of the
      Epstein-Barr virus early antigen (EBV-EA).

PMID- 17191982
TI  - Seed galactomannans: an overview.
AB  - Seed galactomannans are vegetable, heterogeneous polysaccharides widely
      distributed in nature. Generally, they possess (1-->4)-linked D-mannopyranose
      (Man) main chains to which are attached (1-->6)-linked D-galactopyranosyl (Gal)
      units. The Man/Gal ratios differ from gum to gum, resulting in a change in
      structure, which, in turn, determines the various industrial applications of seed
      galactomannans. These materials are important in paper, textile, petroleum
      drilling, pharmaceutics, food, cosmaceutics, and explosives industries. In this
      review, the biodiversified applicability of galactomannan gums is discussed,
      particularly with respect to structural aspects, properties, human consumption,
      and technical applications. Especially important is that the solution properties
      (rheological behaviour, viscosity, emulsifying tendency, etc.) of natural and
      chemically modified galactomannans can be tuned by interaction with other
      (carbohydrate-based) monomers or polymers.

PMID- 17191984
TI  - The agonist paradox: agonists and antagonists of acetylcholine receptors and
      opioid receptors.
AB  - In contrast to antagonists, agonists tend to induce considerable conformational
      changes in their receptors, resulting in opening of ion channels, either directly
      or via secondary messengers. These conformational transformations require great
      energy expenses. However, the experimentally determined free energies of
      complexation between agonists and receptors are often relatively smaller than
      those for the corresponding antagonists. To rationalize this so-called 'agonist
      paradox', which has not been clarified in the literature, we have developed an
      alternative model. Our model may help to discriminate between agonists and
      antagonists of the acetylcholine (ACh) and mu-opioid receptors. For this purpose,
      a series of ligands (1-18) have been analyzed both in structural terms and with
      respect to complexation geometry within the anionic binding sites of these two
      receptor types.

PMID- 17191983
TI  - Volatile organic compounds from arctic bacteria of the Cytophaga-Flavobacterium
      Bacteroides group: a retrobiosynthetic approach in chemotaxonomic investigations.
AB  - Volatile organic compounds emitted by different marine arctic strains of the
      Cytophaga-Flavobacterium-Bacteroides group were investigated by using a modified
      closed-loop stripping apparatus (CLSA). Seven of nine strains emitted volatiles,
      dominated by methyl ketones, in specific patterns. The methyl ketones were
      aliphatic saturated, or unsaturated, and comprised 12 to 18 C-atoms, sometimes
      with terminal Me branches. They were identified by GC/MS, retention-index
      calculations, derivatization with dimethyl disulfide for C=C bond location, and
      GC/FTIR to elucidate their uniform (Z)-configuration. The proposed structures of
      all methyl ketones were subsequently confirmed by synthesis, while the absolute
      configuration of chiral volatiles was elucidated by stereoselective synthesis.
      From retrobiosynthetic considerations, it was found that strain ARK10267 uses
      mainly valine, and strain ARK10063 mainly isoleucine for formation of starters
      for the ketone biosynthesis, which is correlated to fatty acid biosynthesis. Four
      strains (ARK10223, ARK10044, ARK10141, and ARK10146) use leucine. These
      separations are supported by phylogenetic affiliations based on 16S rRNA. Strain
      ARK10255b, in the course of this study found to be not a member of the Cytophaga
      Flavobacterium-Bacteroides phylum, did not emit aliphatic ketones of medium chain
      length, but methionine-derived 4-(methylsulfanyl)butan-2-one and corresponding 4
      (methylsulfanyl)butan-2-ol. Most of the compounds described have not been
      reported previously from nature.

PMID- 17191985
TI  - Antioxidant quinonemethide triterpenes from Salacia campestris.
AB  - A new quinonemethide triterpene named as salacin, has been isolated from the root
      bark of Salacia campestris in addition to the known pristimerin, maytenin,
      20alpha-hydroxymaytenin, and netzahualcoyene. Salacin was identified on the basis
      of NMR-spectral and mass spectrometric analysis. The free-radical scavenging
      activities of the quinonemethide triterpenes salacin (1), pristimerin (2),
      maytenin (3), 20alpha-hydroxymaytenin (4), and netzahualcoyene (5) towards DPPH
      have been evaluated and showed absorbance variation (deltaA) of 19, 20, 39, 28,
      55, and 10%, respectively, having rutin (74% at 50 microM) and BHT (7% at 50
      microM) as standard compounds.

PMID- 17191986
TI  - Sorption of lead, cadmium, and zinc on sulfur-containing chemically modified
      wastes of fluted pumpkin (Telfairia occidentalis Hook f.).
AB  - We have tested the applicability of regular as well as sulfanylacetic acid (SA)
      modified fluted pumpkin waste biomass as adsorbents for Pb2+, Cd2+, and Zn2+
      aqueous solutions by means of the batch-sorption technique. The data revealed
      that SA modification produces a larger surface area, enhancing the metal-ion
      binding capacity of the biomass. The sorption process was examined by means of
      Freundlich and Langmuir models. The kinetic study showed that the sorption rates
      can be described by a pseudo-second-order process. The rate constants for the
      control biomass (CB) were 2.2x10(-2), 4.4x10(-2), and 1.6x10(-2) mg g(-1) min(-1)
      for Pb2+, Cd2+, and Zn2+, respectively; and the corresponding rate constants for
      the SA-modified biomass were 4.0x10(-2), 4.7x10(-2), and 1.7x10(-2) mg g(-1) min(
      1), respectively. Thermodynamic considerations indicated a spontaneous exothermic
      process, which implies that physisorption is the main mechanism in the sorption
      process.

PMID- 17191987
TI  - Spectrophotometric determination with a chromogenic reagent of lead in
      vegetables.
AB  - A method was developed for the simple, selective, and sensitive
      spectrophotometric determination of lead in vegetables with synthesized
      chromogenic reagent 3-[(2,6-dibromo-4-methylphenyl)diazenyl]-4,5-dihydroxy-6
      [(2,4,6-tribromophenyl)diazenyl]naphthalene-2,7-disulfonic acid (DBMTBA; 1). In
      0.25 M phosphoric acid medium, which greatly increases the selectivity, lead
      reacts with DBMTBA to form a 1:2 blue complex, which shows maximum absorption at
      646 nm. Under optimal conditions, Beer's law is obeyed over the range from 0.09
      to 0.8 microg ml(-1) Pb2+, and the apparent molar absorptivity is 1.024x10(5) l
      mol(-1) cm(-1). The detection limit and the variation coefficient were found to
      be 2.09 microg ml(-1) and 1.0%, resp. The proposed method has been applied
      successfully for the determination of lead in vegetables (Solanum melongena
      fruits, tomato fruits, Ablemoschus esculentus leaves, and Daucous carota leaves)
      with satisfactory results.

PMID- 17191988
TI  - Microbial transformation of mesterolone.
AB  - The microbial transformation of mesterolone (= (1alpha,5alpha,17beta)-17-hydroxy
      1-methylandrostan-3-one; 1), by a number of fungi yielded (1alpha,5alpha)-1
      methylandrostane-3,17-dione (2), (1alpha,3beta,5alpha,17beta)-1-methylandrostane
      3,17-diol (3), (5alpha)-1-methylandrost-1-ene-3,17-dione (4),
      (1alpha,5alpha,15alpha)-15-hydroxy-1-methylandrostane-3,17-dione (5),
      (1alpha,5alpha,6alpha,17beta)-6,17-dihydroxy-1-methylandrostan-3-one (6),
      (1alpha,5alpha,7alpha,17beta)-7,17-dihydroxy-1-methylandrostan-3-one (7),
      (1alpha,5alpha,11alpha,17beta)-11,17-dihydroxy-1-methylandrostan-3-one (8),
      (1alpha,5alpha,15alpha, 17beta)15,17-dihydroxy-1-methylandrostan-3-one (9), and
      (5alpha,15alpha,17beta)-15,17-dihydroxy-1-methylandrost-1-en-3-one (10).
      Metabolites 5-10 were found to be new compounds. All metabolites, except 2, 3, 6,
      and 7, exhibited potent anti-inflammatory activity. The structures of these
      metabolites were characterized on the basis of spectroscopic studies, and the
      structure of 5 was also determined by single-crystal X-ray-diffraction analysis.

PMID- 17191989
TI  - Exploring the antibacterial and hemolytic activity of shorter- and longer-chain
      beta-, alpha,beta-, and gamma-peptides, and of beta-peptides from beta2-3-aza-
      and beta3-2-methylidene-amino acids bearing proteinogenic side chains--a survey.
AB  - The antibacterial activities of 31 different beta-, mixed alpha/beta-, and gamma
      peptides, as well as of beta-peptides derived from beta2-3-aza- and beta3-2
      methylidene-amino acids were assayed against six pathogens (Enterococcus
      faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli,
      Klebsiella pneumoniae, and Pseudomonas aeruginosa), and the results were compared
      with literature data. The interaction of these peptides with mammalian cells, as
      modeled by measuring the hemolysis of human erythrocytes, was also investigated.
      In addition to those peptides designed to fold into amphiphilic helical
      conformations with positive charges on one face of the helix, one new peptide
      with hemolytic activity was detected within the sample set. Moreover, it was
      demonstrated that neither cationic peptides used for membrane translocation
      (beta3-oligoarginines), nor mixed alpha/beta- or gamma-peptides with somatostatin
      mimicking activities display unwanted hemolytic activity.

PMID- 17191990
TI  - Cancer chemopreventive activity of lupane- and oleanane-type triterpenoids from
      the cones of Liquidamber styraciflua.
AB  - In a search for cancer chemopreventive agents from natural sources, four lupane
      type and seven oleanane-type triterpenoids, and ten synthetic analogs were
      screened as potential anti-tumor promoters by using the in vitro short-term 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen
      (EBV-EA) activation assay. Among them, 25-acetoxy-3alpha-hydroxyolean-12-en-28
      oic acid (1) and 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (2) were
      examined for anti-tumor promoting activity in a two-stage carcinogenesis assay on
      mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) and TPA as promoter. 25
      Acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3beta,25-epoxy-3alpha
      hydroxylup-20(29)-en-28-oic acid (2) showed moderate inhibitory activities.

PMID- 17191992
TI  - Utilization of a common pathway for the synthesis of high affinity macrocyclic
      Grb2 SH2 domain-binding peptide mimetics that differ in the configuration at one
      ring junction.
AB  - As typified by 2-{(9S,10S,14R,18S)-18-(2-amino-2-oxoethyl)-14-[(5-methyl-1H-indol
      1-yl)methyl]-8,17,20-trioxo-10-[4-(phosphonomethyl)phenyl]-7,16,19
      triazaspiro[5.14]icos-11-en-9-yl}acetic acid ((14R)-1b), ring-closing methathesis
      derived macrocyclic tetrapeptide mimetics have recently been reported that bind
      with high affinity to Grb2 SH2 domains in both extracellular and whole-cell
      assays. The synthetic complexity of this class of agents limits further
      therapeutic development. Although a significant component of this synthetic
      complexity arises from the presence of three stereogenic centers, C(9) (S), C(10)
      (S), and C(14) (R), it is unclear whether stereoselective introduction of defined
      configuration at C(14) is required for high-affinity binding. Reported herein is
      a synthetic route to these macrocycles lacking stereoselectivity in the formation
      of the C(14) ring junction, which is four synthetic steps shorter than the
      original stereoselective synthesis. Separation of C(14)-epimers obtained by this
      approach was achieved by preparative HPLC. Molecular-dynamics studies of ligands
      bound to the Grb2 SH2 domain protein indicated that the (14R)-configuration
      should display more-favorable interactions with the protein relative to the (14S)
      epimer. Indeed, although surface-plasmon-resonance-derived binding constants to
      Grb2 SH2 domain protein indicated that the affinity of the (14R)-epimer (KD = 4.8
      nM) is greater than that of the (14S)-epimer (KD = 11 nM), it is only marginally
      so. Therefore, little affinity would be lost through a non-stereoselective
      synthesis of the C(14)-center. Further studies are in progress to explore reduced
      structural complexity at the C(14)-center.

PMID- 17191991
TI  - Exploring the mechanisms of molecular recognition by flavins.
AB  - The design and development of chemical models for enzymes depends on the
      fundamental principles observed in biological systems. Molecular recognition of
      flavins by various receptors has attracted attention due to their applications as
      chemical models for flavoenzymes. The area of molecular recognition is being
      investigated through research at the interface of chemistry and biology. In this
      review, the literature has been surveyed to provide comprehensive coverage of the
      synthetic methodology of different flavins and receptors and their molecular
      recognition studies. Various applications of flavin-receptor complexes have also
      been highlighted.

PMID- 17191993
TI  - Structure elucidation and phytotoxicity of ecdysteroids from Chenopodium album.
AB  - The leaves of Chenopodium album were infused in H2O/MeOH. The extract treated
      with cold acetone gave heavy precipitation, which was removed by centrifugation.
      Solid material was fractionated into acidic and neutral fractions. The acidic
      material was subjected to different silica-gel column chromatographies, and then
      it was purified by reversed-phase HPLC to afford four known ecdysteroids and the
      new 3beta,14alpha-dihydroxy-5beta-pregn-7-ene-2,6,20-trione that were
      characterized by extensive spectroscopic investigation, especially by 1D- and 2D
      NMR. Their effects on germination and growth of Lactuca sativa L. have been
      studied. The results are reported as percentage differences of germination, root
      elongation and shoot elongation, from the control at concentrations ranging from
      10(-4) to 10(-7) M.

PMID- 17191994
TI  - Aryl ketones from Acronychia pedunculata with cyclooxygenase-2 inhibitory
      effects.
AB  - 1-[2,4-Dihydroxy-6-methoxy-3,5-bis(3-methylbut-2-en-1-yl)phenyl]ethanone (1), and
      a new aryl ketone, named acrovestenol (2), were isolated as cyclooxygenase-2 (COX
      2) inhibitory principles from a CH2Cl2 extract of the bark of Acronychia
      pedunculata by a bioassay-guided fractionation procedure. Compound 2 inhibited
      COX-2 with an IC50 value of 142.0+/-2.15 microM, compared to the COX-2 inhibitory
      reference compound NS-398 with an IC50 value of 11.3+/-1.12 microM. Compound 1
      inhibited COX-2-catalyzed PG biosynthesis with 68% at a concentration of 500
      microM. The structures were determined by UV, IR, and 1D- and 2D-NMR, including
      TOCSY, HSQC-DEPT, and HMBC, and MS investigations.

PMID- 17191995
TI  - Synthesis of methyl ether analogues of sildenafil (Viagra) possessing tyrosinase
      inhibitory potential.
AB  - The microwave-assisted synthesis and characterization of the ten new sildenafil
      (Viagra; 1) analogues 6-15 are described. A detailed structure-activity
      relationship (SAR) study revealed that compounds 10 (= 4-ethoxy-N-hydroxy-3-(7
      methoxy-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonamide)
      and 12 (= S-(2-hydroxyethyl) 4-ethoxy-3-(7-methoxy-1-methyl-3-propyl-1H
      pyrazolo[4,3-d]pyrimidin-5-yl)benzenesulfonothioate) are extremely potent
      mushroom tyrosinase inhibitors, with IC50 values (3.59 and 2.15 microM, resp.)
      below those of the standard inhibitors L-mimosine and kojic acid (IC50 = 3.68 and
      16.67 microM, resp.). Compounds 10 and 12 are, thus, the currently most-effective
      inhibitors of tyrosinase, and bear great potential to be used for the treatment
      of various skin disorders such as hyperpigmentation, which is associated with
      high production of melanocytes.

PMID- 17191996
TI  - Inductively coupled plasma-optical emission spectrometry for on-line
      determination of multi trace elements in environmental samples after
      preconcentration by using Borassus flabellifer inflorescence loaded with 2
      propylpiperidine-1-carbodithioate.
AB  - A procedure was developed for the determination of Cu, Mn, Pb, Cd, Co, Cr, and Zn
      in water samples by Inductively Coupled Plasma-Optical Emission Spectrometry (ICP
      OES) after preconcentration on synthesized 2-propylpiperidine-1-carbodithioate
      supported by Borassus flabellifer Inflorescence (BFI). The sorbed element was
      subsequently eluted with 0.4 M HNO3, and the acid eluates were analyzed by ICP
      OES. The influence of various parameters such as pH, flow rate of sample, eluent
      concentration, volume of the sample, and volume of eluent were investigated.
      Under the optimal conditions, Cu, Mn, Pb, Cd, Co, Cr, and Zn in aqueous samples
      were concentrated ca. 100-fold. Recoveries were obtained by the proposed method
      in the range of 97.8-99.9%. This method was also applied for the analysis of
      spiked, natural waters and soil samples. The results provide strong evidence to
      support the hypothesis of an adsorption mechanism.

PMID- 17191997
TI  - Syntheses and biological activities of chalcone and 1,5-benzothiazepine
      derivatives: promising new free-radical scavengers, and esterase, urease, and
      alpha-glucosidase inhibitors.
AB  - A series of 2,4-diaryl-2,3,4,5-tetrahydro- (36-40) and 2,4-diaryl-2,3-dihydro-1,5
      benzothiazepines (25-35) have been synthesized from the corresponding chalcones 1
      24. Both the benzothiazepines and chalcones were evaluated as DPPH free-radical
      scavengers and as inhibitors of cholinesterases, urease, and alpha-glucosidase.
      Compounds 2, 5, 6, 7, 10, 13, 18, 21, 36a, 37a, 37b, and 39a showed significant
      cholinesterase inhibiting activities. Among the 15 dihydro-1,5-benzothiazepines,
      26, 32, and 35 exhibited significant radical-scavenging activities; and six
      tetrahydro-1,5-benzothiazepines (35, 36a, 36b, 37a, 37b, and 39a) were found to
      be inhibitors of AChE and BChE. Compounds 22, 25, 26, 33, 35, 36a, 37b, and 39a
      inhibited urease, and 25 and 27-31 were found to be potent inhibitors of alpha
      glucosidase.

PMID- 17191998
TI  - Norlignans from Sequoia sempervirens.
AB  - Six new norlignans, named sequosempervirins B-G (1-6), together with three known
      norlignans, agatharesinol (7), agatharesinol acetonide (8), and sugiresinol (9),
      were isolated from the branches and leaves of Sequoia sempervirens. Their
      structures were determined mainly by high-resolution mass spectroscopy (HR-MS),
      and various 1D- and 2D-NMR methods, as well as, in the case of 1, by means of X
      ray diffraction. Compound 8 showed anticancer activity towards the A549 non-small
      cell lung-cancer cell line (IC50 = 27.1 microM). The acetone extract of S.
      sempervirens was found to be antifungal towards Candida glabrata (IC50 = 15.98
      microg/ml), and both the acetone and MeOH extracts inhibited the proteolytic
      activity of cathepsin B (IC50 = 4.58 and 5.49 microg/ml, resp.).

PMID- 17191999
TI  - Formation of a new oxidative metabolite from kobophenol A by human intestinal
      bacterium Klebsiella pneumoniae.
AB  - During our studies on the metabolism of kobophenol A (1) in rats, we had
      isolated, purified, and identified the main new oxidative metabolite of 1,
      koboquinone A (2) from rats' feces. To elucidate the metabolic pathway of 1 in
      rats, we conducted the in vitro metabolic experiments of 1 by human intestinal
      bacteria and found that Klebsiella pneumoniae produced appreciable amounts of 2.
      This was verified by means of high performance liquid chromatography mass/mass
      spectrometry (HPLC/MS/MS) analysis.

PMID- 17192001
TI  - Fungal metabolites of (E)-guggulsterone and their antibacterial and radical
      scavenging activities.
AB  - Fungal transformation of (E)-guggulsterone (= (17E)-pregna-4,17-diene-3,16-dione;
      1) by Rhizopus stolonifer, Fusarium lini, Cunninghamella elegans, or Gibberella
      fujikuroi afforded ten hydroxylated metabolites (2-11; Scheme), which were fully
      characterized. Compounds 4-11 have not been described yet. Some of these novel
      hydroxylated metabolites, as well as acetylated derivatives thereof, exhibited
      significant antibacterial and radical-scavenging activities (Table 3).

PMID- 17192000
TI  - Immunological-adjuvant saponins from the roots of Panax notoginseng.
AB  - The total saponin extract from the dried roots of Panax notoginseng (Burk.) F. H.
      Chen possesses immunological-adjuvant activities. Guided by in vivo immunological
      tests, further study on this fraction afforded three active dammarane-type
      saponins. Their structures were determined on the basis of chemical evidence and
      extensive spectroscopic methods, including 1D- and 2D-NMR. The novel compound
      (20S)-protopanaxatriol 20-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside
      (1), and the two known compounds ginsenoside Rh4 (2) and notoginsenoside K (3)
      exhibited immunological-adjuvant activities on the humoral immune responses of
      ICR mice against ovalbumin (OVA).

PMID- 17192002
TI  - Structure determination of a tetrahydro-beta-carboline of arthropod origin: a
      novel alkaloid-toxin subclass from the web of spider Nephila clavipes.
AB  - The orb-web spiders are polyphagous animals in which the web plays a very
      important role in the capture of preys; oily droplets usually cover the capture
      web of the spider Nephila clavipes and seem to be of great importance for prey
      capture. The knowledge of the chemical composition of these droplets is necessary
      to understand the function of this adhesive material in web mechanics and prey
      capture. A novel subclass of spider toxins, tetrahydro-beta-carboline, was
      identified among the weaponry of compounds present inside of oily droplets. This
      type of alkaloid is not common among the natural compounds of spider toxins.
      Apparently, when the prey arthropods get caught by the spider web, their bodies
      are covered with many adhesive oily droplets, which disrupt delivering the
      tetrahydro-beta-carboline to the direct contact with the prey integument.
      Toxicity assays demonstrated a potent lethal effect of the alkaloid toxin to the
      spider preys; topical applications of the tetrahydro-beta-carboline at first
      caused clear signs of neurotoxicity, followed by the death of preys. The
      structure of the major component, a tetrahydro-beta-carboline, among the alkaloid
      toxins was elucidated by means of UV spectrophotometry, ESI mass spectrometry, 1H
      NMR spectroscopy, and high-resolution mass spectrometry. The structure of the
      natural toxin was determined as 1-(2-guanidinoethyl)-1,2,3,4-tetrahydro-6
      hydroxymethyl)-beta-carboline; the investigation of the pharmacological
      properties and neurotoxic actions of this compound may be used in the future as
      reference for the development of new drugs to be applied at level of pest control
      in agriculture.

PMID- 17192003
TI  - Solution structure of delta-Am2766: a highly hydrophobic delta-conotoxin from
      Conus amadis that inhibits inactivation of neuronal voltage-gated sodium
      channels.
AB  - The three-dimensional (3D) NMR solution structure (MeOH) of the highly
      hydrophobic delta-conotoxin delta-Am2766 from the molluscivorous snail Conus
      amadis has been determined. Fifteen converged structures were obtained on the
      basis of 262 distance constraints, 25 torsion-angle constraints, and ten
      constraints based on disulfide linkages and H-bonds. The root-mean-square
      deviations (rmsd) about the averaged coordinates of the backbone (N, C(alpha), C)
      and (all) heavy atoms were 0.62+/-0.20 and 1.12+/-0.23 A, respectively. The
      structures determined are of good stereochemical quality, as evidenced by the
      high percentage (100%) of backbone dihedral angles that occupy favorable and
      additionally allowed regions of the Ramachandran map. The structure of delta
      Am2766 consists of a triple-stranded antiparallel beta-sheet, and of four turns.
      The three disulfides form the classical 'inhibitory cysteine knot' motif. So far,
      only one tertiary structure of a delta-conotoxin has been reported; thus, the
      tertiary structure of delta-Am2766 is the second such example. Another Conus
      peptide, Am2735 from C. amadis, has also been purified and sequenced. Am2735
      shares 96% sequence identity with delta-Am2766. Unlike delta-Am2766, Am2735 does
      not inhibit the fast inactivation of Na+ currents in rat brain Na(v)1.2 Na+
      channels at concentrations up to 200 nM.

PMID- 17192004
TI  - Design, synthesis, and biological evaluation of new territrem B analogues.
AB  - Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B
      (1) were designed, synthesized, and tested for their biological activities. Some
      of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the
      upper micromolar range. Molecular-modeling studies indicated that a planar
      conformation seems to be crucial for AChE inhibition. The two N-atoms of the
      piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory
      effects. The cytotoxicities of selected compounds against six human tumor cell
      lines were also determined.

PMID- 17192005
TI  - Biotransformation of terpenoids by mammals, microorganisms, and plant-cultured
      cells.
AB  - This review article summarizes our knowledge of the metabolism of mono- and
      sesquiterpenoids in mammals, microorganisms, cloned-insect enzymes, and plant
      cultured cells. A number of unusual enzymatic reactions and products are reported
      such as the stereoselective formation of primary alcohols from sterically
      congested Me2C groups. Such enzymatic processes, including unknown chemical
      transformations under abiotic conditions, could lead to the discovery of new
      chemical reactions and might be helpful in the design of new drugs. The
      transformations of the following mono- and sesquiterpenoids (in alphabetical
      order) are discussed: (+)-(1R)-aromadendrene (61), (-)-allo-aromadendrene (62),
      (+/-)-camphene (21), (-)-cis-carane (20), (+)-3-carene (17), (+/-)-carvone (27),
      (-)-beta-caryophyllene (43), (+)-cedrol (35), cuminaldehyde (25), (+)-curdione
      (69), (-)-cyclocolorenone (60), (-)-elemol (51), (2E,6E)-farnesol (31),
      germacrone (67), ginsenol (40), (-)-globulol (63), isoprobotryan-9alpha-ol (82a),
      juvenile hormone III (33), (+)-ledol (65), (+)-longifolene (46), myrcene (3), (-)
      myrtenal (23), (+)-nootkatone (48), patchouli alcohol (37), (-)-perillaldehyde
      (24), (-)-alpha- and beta-pinene (8 and 9), alpha-santalol (28), (-)-6beta
      santonin (83a), 6beta-tetrahydrosantonin (83b), beta-selinene (57), alpha-thujone
      (26a), beta-thujone (26b), T-2 toxin (87), and valerianol (53).

PMID- 17192006
TI  - The proteolytic stability of 'designed' beta-peptides containing alpha-peptide
      bond mimics and of mixed alpha,beta-peptides: application to the construction of
      MHC-binding peptides.
AB  - Whereas alpha-peptides are rapidly degraded in vivo and in vitro by a multitude
      of peptidases, substrates constructed entirely of or incorporating homologated
      alpha-amino acid (i.e., beta-amino acid) units exhibit a superior stability
      profile. Efforts made so far to proteolytically hydrolyze a beta-beta peptide
      bond have not proved fruitful; a study aimed at breaching this proteolytic
      stability is discussed here. A series of such bonds have been designed with side
      chain groups similar in relative positions (constitution) and three-dimensional
      arrangements (configuration) as found about alpha-peptidic amide bonds.
      Increasing the prospect for degradation would permit the tuning of beta-peptide
      stability; here, however, no cleavage was observed (1, 2, 4-6, Table 1). Peptides
      comprised of alpha- and beta-amino acids (mixed alpha,beta-peptides, 8-11) are
      expected to benefit from both recognition by a natural receptor and a high level
      of proteolytic stability, ideal characteristics of pharmacologically active
      compounds. Beta3-peptides containing alpha-amino acid moieties at the N-terminus
      are degraded, albeit slowly, by several peptidases. Of particular interest is the
      ability of pronase to cleave an alpha-beta peptide bond, namely that of alphaAla
      beta3 hAla. Significantly, successful hydrolysis is independent of the
      configuration of the beta-amino acid. Some of the alpha,beta-peptides discussed
      here are being investigated for their binding affinities to class I MHC proteins.
      The computer-programming steps required to prepare alpha,beta-peptides on an
      automated peptide synthesizer are presented.

PMID- 17192007
TI  - Neural networks in chemosystematic studies of Asteraceae: a classification based
      on a dichotomic approach.
AB  - This paper describes the application of artificial neural nets as an alternative
      and efficient method for the classification of botanical taxa based on chemical
      data (chemosystematics). A total of 28,000 botanical occurrences of chemical
      compounds isolated from the Asteraceae family were chosen from the literature,
      and grouped by chemical class for each species. Four tests were carried out to
      differentiate and classify different botanical taxa. The qualifying capacity of
      the artificial neural nets was dichotomically tested at different hierarchical
      levels of the family, such as subfamilies and groups of Heliantheae subtribes.
      Furthermore, two specific subtribes of the Heliantheae and two genera of one of
      these subtribes were also tested. In general, the artificial neural net gave rise
      to good results, with multiple-correlation values R>0.90. Hence, it was possible
      to differentiate the dichotomic character of the botanical taxa studied.

PMID- 17192008
TI  - Molecular modeling of Henry-Michaelis and acyl-enzyme complexes between imipenem
      and Enterobacter cloacae P99 beta-lactamase.
AB  - We report a molecular-mechanics (AMBER*) study on the Henry-Michaelis complex and
      the corresponding acyl-enzyme adduct formed between imipenem (1), a transient
      inhibitor of beta-lactamases, and Enterobacter cloacae P99, a class C-beta
      lactamase. We have examined the influence of the structural configuration of the
      functional groups in the substrate on their three-dimensional (3D) arrangement at
      the active site, which was compared with those adopted by typical penicillins and
      cephalosporins. Our results confirm that the carboxy group of the antibiotic
      plays a prominent role in the binding of the substrate to the active site, and
      that it activates Ser64 through interaction with the phenolic OH group of Tyr150.
      The binding of imipenem to E. cloacae P99 increases the distance between Tyr150
      and Ser64 due to the presence of a hydrophobic Me group in the (R)-1-hydroxyethyl
      substituent at C(6). This, together with the 3D arrangement of its carboxy group,
      leads to an interaction with the active site in a manner that hinders H+ exchange
      between the nucleophile in Ser64 and its basic activator, the phenolic group of
      Tyr150.

PMID- 17192009
TI  - Improved anti-inflammatory activity of three new terpenoids derived, by
      systematic chemical modifications, from the abundant triterpenes of the flowery
      plant Calendula officinalis.
AB  - Rings A, D and E of faradiol (1), and ring E of both arnidiol (10) and
      calenduladiol (4) have been subjected to various selective chemical manipulations
      to modify polarity, water affinity, H-bonding, sterics, and number of aromatic
      groups of these anti-inflammatory natural compounds. A total of 15 new and four
      known pentacyclic triterpenoids have been obtained in this way. Some 13
      terpenoids were evaluated for their topical anti-inflammatory activities with
      respect to inhibition of croton oil induced ear oedema in mouse. Three
      derivatives of 1, the C(16) benzyl ether 15, the C(30) aldehyde 24, and the C(30)
      primary alcohol 25 showed significantly improved anti-inflammatory potencies,
      which is relevant for (future) structure-activity-relationship (SAR) studies.

PMID- 17192010
TI  - Ternary zinc(II)-dipeptide complexes for the hydrolytic cleavage of DNA at
      physiological pH.
AB  - A series of Zn(II) complexes with cysteinylglycine (CysGly) and histidylserine
      (HisSer), and of CysGly and histidylphenylalanine (HisPhe) were investigated.
      Complex stabilities were determined potentiometrically, and binding geometries
      were probed by means of 1H-NMR spectroscopy, using Co(II) instead of Zn(II) as a
      spectroscopic marker. The ternary 1:1:1 complexes [Zn(II)(CysGly)(HisSer)] and
      [Zn(II)(CysGly)(HisPhe)] were shown by UV experiments, fluorescence titration,
      and gel electrophoresis to intercalate with DNA, and to hydrolytically cleave
      supercoiled DNA (form-I), partly also circular (form-II) DNA, under physiological
      conditions (37 degrees, H2O, pH 7.5).

PMID- 17192011
TI  - Larvicidal activity of Acacia nilotica extracts and isolation of D-pinitol--a
      bioactive carbohydrate.
AB  - A low-molecular-weight, sugar-like compound other than glucose, fructose,
      sucrose, or myo-inositol showing lipophilic nature was isolated from the EtOH
      extract of Acacia nilotica. The structure of the compound was determined by
      spectral methods. This alicyclic polyalcohol was found to be D-pinitol (= 3-O
      methyl-D-chiro-inositol; 1). The configuration of the compound was confirmed by
      single-crystal X-ray analysis. The compound 1 is known from Soybean, Australian
      mangroves, Fagonia indica, Arachis hypogaea, etc., but we have isolated this
      compound for the first time from the aerial parts of A. nilotica. Very few
      references have been cited for compound 1 for its entomological activity, and
      there are no reports on mosquitoes. Therefore, the crude extracts of A. nilotica
      were tested for its biological activity against mosquito larvae. Acetone extract
      at 500-ppm concentration showed chronic toxicity against Aedes aegypti and Culex
      quinquefasciatus IVth instar mosquito larvae. Such a biological activity has been
      observed for the first time for this plant. This study could be a stepping stone
      to a solution for destroying larval species as well as consumption of such a
      widely grown, problem weed, A. nilotica. This larvicidal agent, since it is
      derived from plant, is eco-friendly, cost effective, non-hazardous to non-target
      organisms and would be safe unlike commercially available insecticides.

PMID- 17192012
TI  - Betulinic acid and its derivatives, potent DNA topoisomerase II inhibitors, from
      the bark of Bischofia javanica.
AB  - DNA Topoisomerases (Topos) II are target enzymes for anticancer chemotherapeutic
      drug development. Bioassay-guided fractionation of the CHCl3 extract of the bark
      of Bischofia javanica led to the isolation of betulinic acid (1) and its
      derivatives, betulonic acid (2), 3beta-O-(Z)-coumaroylbetulinic acid (3), and
      3beta-O-(E)-coumaroylbetulinic acid (4). These compounds were found to be
      catalytic inhibitors of Topo II activities with IC50 values ranging from 0.38 to
      58 microM. The acylation of the OH group at C(3) of betulinic acid exhibited
      stronger Topo II inhibitory activity.

PMID- 17192013
TI  - Synthesis and cytotoxicity of a novel iridoid glucoside derived from aucubin.
AB  - The novel iridoid glycoside 2 was prepared in six steps (15% overall yield) from
      natural aucubin (1) and fully characterized. Compound 2, which comprises the same
      conjugated cyclopentenone pharmacophore as known antitumor oxylipins and
      prostaglandins, displayed significant antiproliferative in vitro activity towards
      leukemia L1210 cells. The Michael addition of nucleophilic thiols to compound 2
      occurred on a different position compared to classical delta7-prostaglandin A1
      methyl ester. The resulting adducts 7a and 7b were fully characterized, and their
      MS fragmentation patterns were elucidated.

PMID- 17192014
TI  - Identification of the precursor of (S)-3-methyl-3-sulfanylhexan-1-ol, the sulfury
      malodour of human axilla sweat.
AB  - A careful study of human axillary microflora led us to the identification of a
      new strain of Staphylococcus haemolyticus. The role in axillary malodour
      formation of this microorganism was compared to those of Corynebacterium xerosis
      and Staphylococcus epidermidis, upon incubation on sterile human eccrine and
      apocrine axilla sweat. St. haemolyticus was responsible for the strongest sulfury
      malodour and the generation of the volatile sulfur compound (VSC) (S)-3-methyl-3
      sulfanylhexan-1-ol (3). In this study, we investigated the nonvolatile precursors
      of VSCs. Human axillary sweat was collected, fractionated and analysed by
      HPLC/APCI-MS (High-Pressure Liquid Chromatography coupled to Atmospheric Pressure
      Chemical Ionisation Mass Spectrometry). The precursor of 3 was identified as [1
      (2-hydroxyethyl)-1-methylbutyl]-L-cysteinylglycine (Cys-Gly-(S)-conjugate; 12).
      Because Cys-Gly-(S)-conjugates are key intermediates in the glutathione
      biodetoxification pathway, other derivatives of 12, specifically glutathione-(S)
      conjugate 11 and Cys-(S)-conjugate 13, were prepared. Compounds 11 and 13 were
      not detected by HPLC/MS of sterile sweat. Synthetic homologues 11, 12, and 13
      were incubated with C. xerosis, St. heamolyticus, and St. epidermidis. We
      observed efficient conversion of precursors 12 and 13 to form VSCs when incubated
      with St. haemolyticus, with a clear preference for 12. C. xerosis and St.
      epidermidis were less efficient in cleaving Cys-Gly-(S)-conjugate 12 to form the
      corresponding thiol 3. Incubation of glutathione-(S)-conjugate 11 never led to
      the formation of 3 under the experimental conditions employed.

PMID- 17192015
TI  - Contributions of lipid bilayer hosts to structure and activity of multifunctional
      supramolecular guests.
AB  - The question of whether or not the surrounding lipid bilayer host contributes to
      structure and activity of included functional guests is a general topic of
      current scientific concern. We report that synthetic multifunctional pores are of
      use to address this elusive question, because the detection of their catalytic
      activity is membrane independent. According to their salt-rate profiles, unstable
      multifunctional supramolecules with permanent internal charges show highest
      membrane sensitivity, and the dependence of membrane sensitivity on the acidity
      of internal cations exceeds that on supramolecule stability. These results can,
      with all appropriate caution, be interpreted as indications for the existence of
      long-range EMP-ICR interactions (EMP: external membrane pressure, ICR: internal
      charge repulsion) between membrane hosts and functional guests that can, for
      instance, prevent the 'explosion' and promote the 'implosion' of over- and
      undercharged transmembrane barrel-stave supramolecules, respectively.

PMID- 17192016
TI  - 'Quantity over quality': a voice from the Third World.

PMID- 17192017
TI  - Abietane diterpenoids from the roots of some Mexican Salvia species (Labiatae):
      chemical diversity, phytogeographical significance, and cytotoxic activity.
AB  - From the roots of some Mexican Salvia species, classified in subgenus Jungia,
      several diterpenoids belonging to abietane (i.e., 3-7), salvifolane (9-->20,10-
      >6)-diabeoabietane) (i.e., 2), and totarane (i.e., 10) carbocyclic skeletons were
      isolated together with two 20-nor- and one 6,7-secoabietane derivatives, 1 and 9,
      and 8, respectively. While compounds 2-10 were previously known from different
      sources, compound 1 is a new 20-norabietane derivative, whose structure was
      deduced by spectroscopic means and confirmed by X-ray-diffraction analysis. The
      phytogeographical significance of the distribution of 20-norabietanic
      diterpenoids in the genus suggested an evolutionary link between the Chinese and
      New-World Salvias. Compounds 2 and 8 were tested for cell-growth inhibition
      activity against several human cancer cell lines and human normal lymphocytes,
      while 2 showed a moderate cytotoxic activity, 8 exhibited a moderate yet
      selective activity against leukemia cell line.

PMID- 17192018
TI  - Synthesis of novel N1-substituted bicyclic pyrazole amino acids and evaluation of
      their interaction with glutamate receptors.
AB  - N1-substituted bicyclic pyrazole amino acids (S)-9a-9c and (R)-9a-9c, which are
      conformationally constrained analogues of glutamic acid, were prepared via a
      strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested
      for activity at ionotropic and metabotropic glutamate receptors. Some of them
      turned out to be selective for the NMDA receptors, where they behaved as weak
      antagonists. The biological activity is mainly due to the interaction with the
      glutamate binding site, and not with the glycine co-agonist site.

PMID- 17192020
TI  - Four new trimeric stilbene glucosides from Welwitschia mirabilis.
AB  - Four new trimeric stilbene glucosides, mirabilosides C-F (1-4) were isolated from
      MeOH extract of stem and root of Welwitschia mirabilis (Welwitschiaceae) along
      with three known stilbenoids, resveratrol (5), gnemonoside B (6), and gnetin G
      (7). The structures of these compounds were elucidated by spectroscopic methods.

PMID- 17192019
TI  - Analysis of binding interaction between the natural apocarotenoid bixin and human
      serum albumin by circular dichroism and fluorescence spectroscopy.
AB  - Bixin is an important, pharmacologically active dietary cis-carotenoid, but its
      interaction with potential macromolecular targets is completely unexplored. This
      work was aimed to study the binding of bixin to human serum albumin (HSA), the
      most abundant protein in blood plasma. Circular dichroism (CD) spectroscopy in
      combination with UV/VIS absorption spectroscopy and fluorescence quenching
      techniques were applied. Appearance of induced CD bands in the UV- and VIS
      absorption spectral regions indicated the formation of non-covalent carotenoid
      albumin complexes. Shape and spectral position of the extrinsic Cotton effects
      suggested the binding of a single bixin molecule to HSA in chiral conformation.
      Scatchard and non-linear regression analyses of CD titration data resulted in
      similar values for the association constant (Ka = 6.6 and 4.6x10(5) M(-1), resp.)
      and for the number of binding sites (n = 1). The binding interaction was
      independently confirmed by fluorescence-quenching experiment from which the
      binding parameters were also calculated. CD Displacement measurements performed
      with marker ligands established that the main drug binding sites of HSA are not
      involved in binding of bixin. Palmitic acid decreased the amplitude of the
      induced CD bands suggesting a common albumin binding site for bixin and long
      chain fatty acids. The above data indicate that HSA plays a significant role in
      the plasma transportation of bixin and related dietary carboxylic acid
      carotenoids.

PMID- 17192021
TI  - Changes in the fatty-acid profile of cyanide-utilizing Yersinia species.
AB  - A cyanide-utilizing Yersinia species was isolated from the cyanide-bearing gold
      plating industrial wastewater. Analysis of the fatty acid composition of the
      organism revealed that it contains large amounts of saturated fatty acids. The
      unsaturated hydroxy- and cyclopropyl-ring-bearing fatty acids are present in low
      concentrations. A comparison of the fatty acid composition with other Yersinia
      species shows that the genus Yersinia appears homogeneous, and that fatty-acid
      data of Yersiniae do not reflect the distance between Yersiniae species.

PMID- 17192022
TI  - Behavioral response of the borer beetle Hoplocerambyx spinicornis to volatile
      compounds of the tree Shorea robusta.
AB  - Essential oils isolated from leaves (LO), bast (BO), heartwood (HO), and ethereal
      extract of resin (EER) of Shorea robusta were bioassayed with electroantennograph
      (EAG) and wind tunnel to study the behavioral response of male and female
      beetles, Hoplocerambyx spinicornis Newm., the most injurious heartwood borer of
      the tree. LO, BO, HO, and EER were shown to exhibit the electrophysiological
      activity in the female beetle, while LO and BO in the male beetle. In wind-tunnel
      studies, only BO elicited the attractant activity to both the sexes. A possible
      correlation of the constituents of the BO identified by GC/MS with the
      bioactivity is also presented.

PMID- 17192024
TI  - Revision of the absolute configuration of plumericin and isoplumericin from
      Plumeria rubra.
AB  - The absolute configurations of plumericin (1) and isoplumericin (2), isolated
      from Plumeria rubra, were re-assigned based on a combination of X-ray crystal
      structure determination and quantum-mechanical calculations of their circular
      dichroism (CD) spectra. The experimental CD spectra showed an excellent match
      with those calculated for the (1S,5R,8R,9R,10R) absolute configuration
      (corresponding to ent-1 and ent-2, resp.), opposite to that generally accepted
      and published in the literature. Since the (false) plumericin configuration has
      been often used to derive the absolute configuration of related iridoids by
      chemical correlation, their absolute configurations also have to be reconsidered.

PMID- 17192023
TI  - Chemical constituents and antioxidant activity of Mallotus roxburghianus leaves.
AB  - Mallotus roxburghianus is used in the traditional medicine in North-Eastern
      India, but previously no work has been done on the identification of bioactive
      compounds. Two new compounds, 3-(1-C-beta-D-glucopyranosyl)-2,6-dihydroxy-5
      methoxybenzoic acid (6) and 2,4,8,9,10-pentahydroxy-3,7-dimethoxyanthracene-6-O
      beta-D-rhamnopyranoside (7) together with beta-sitosterol (1), stigmasterol (2),
      betulinic acid (3), 4-hydroxybenzoic acid (4), beta-sitosterol-beta-D-glucoside
      (5), and bergenin (8) were isolated and identified from the leaves of M.
      roxburghianus. The chloroform soluble portion of the alcoholic extract of leaf,
      and compounds 3, 6, 7, and 8 exhibited encouraging antioxidant activities.

PMID- 17192025
TI  - The studies of density, apparent molar volume, and viscosity of bovine serum
      albumin, egg albumin, and lysozyme in aqueous and RbI, CsI, and DTAB aqueous
      solutions at 303.15 K.
AB  - Density (rho), apparent molar volume (V(phi)), and viscosity (eta) of 0.0010 to
      0.0018% (w/v) of bovine serum albumin (BSA), egg albumin, and lysozyme in 0.0002,
      0.0004, and 0.0008 M aqueous RbI and CsI, and (dodecyl)(trimethyl)ammonium
      bromide (DTAB) solutions were obtained. The experimental data were regressed
      against composition, and constants are used to elucidate the conformational
      changes in protein molecules. With salt concentration, the density of proteins is
      found to decrease, and the order of the effect of additives on density is
      observed as CsI > RbI > DTAB. The trend of apparent molar volume of proteins is
      found as BSA > egg-albumin > lysozyme for three additives. In general, eta values
      of BSA remain higher for all compositions of RbI than that of egg-albumin for CsI
      and DTAB. These orders of the data indicate the strength of intermolecular forces
      between proteins and salts, and are helpful for understanding the denaturation of
      proteins.

PMID- 17192026
TI  - Asymptomatic spontaneous cerebral emboli and cognitive decline in a cohort of
      older people: a prospective study.
AB  - BACKGROUND: Asymptomatic spontaneous cerebral emboli (SCE) are common in dementia
      and are associated with cognitive decline in dementia. The significance of their
      presence in older people is unknown. METHOD: We included 96 participants (mean
      (SD) age 76.8 (6.7) years, 46% female) who were the control group in a case
      control study to evaluate SCE in dementia. Cognitive functioning was assessed
      prospectively over 2.5 years, using the MMSE and CAMCOG. RESULTS: The mean (SD)
      MMSE score was 28.7 (1.4) at baseline with an average (SD) drop of 0.79 (0.91)
      per year. The presence of SCE was not related to the annual drop in MMSE score,
      nor to the CAMCOG score at follow-up (p = 0.88 and p = 0.41, respectively).
      Linear regression analyses identified higher age in years (beta = 0.29, p =
      0.003), history of stroke (beta = 0.31, p = 0.001) and carotid stenosis (beta =
      0.28, p = 0.003) as independent predictors of cognitive decline. CONCLUSION: We
      found no association between the presence of SCE and subsequent cognitive decline
      in older people without dementia.

PMID- 17192027
TI  - Cancer biomarkers: an emerging means of detecting, diagnosing and treating
      cancer.

PMID- 17192028
TI  - Aflatoxin and hepatitis B virus biomarkers: a paradigm for complex environmental
      exposures and cancer risk.
AB  - The use of biomarkers in molecular epidemiology studies for identifying stages in
      the progression of development of the health effects of environmental agents has
      the potential for providing important information for critical regulatory,
      clinical and public health problems. Investigations of aflatoxins probably
      represents one of the most extensive data sets in the field and this work may
      serve as a template for future studies of other environmental agents. The
      aflatoxins are naturally occurring mycotoxins found on foods such as corn,
      peanuts, various other nuts and cottonseed and they have been demonstrated to be
      carcinogenic in many experimental models. As a result of nearly thirty years of
      study, experimental data and epidemiological studies in human populations,
      aflatoxin B(1) was classified as carcinogenic to humans by the International
      Agency for Research on Cancer. The long-term goal of the research described
      herein is the application of biomarkers to the development of preventative
      interventions for use in human populations at high-risk for cancer. Several of
      the aflatoxin specific biomarkers have been validated in epidemiological studies
      and are now being used as intermediate biomarkers in prevention studies. The
      development of these aflatoxin biomarkers has been based upon the knowledge of
      the biochemistry and toxicology of aflatoxins gleaned from both experimental and
      human studies. These biomarkers have subsequently been utilised in experimental
      models to provide data on the modulation of these markers under different
      situations of disease risk. This systematic approach provides encouragement for
      preventive interventions and should serve as a template for the development,
      validation and application of other chemical-specific biomarkers to cancer or
      other chronic diseases. This systematic approach provides encouragement for
      preventive interventions and should serve as a template for the development,
      validation and application of other chemical-specific biomarkers to cancer or
      other chronic diseases.

PMID- 17192029
TI  - Current status and future directions for diagnostic markers of drug-induced
      vascular injury.
AB  - Recently, there has been an increased incidence of vascular toxicity in pre
      clinical toxicology studies. This is of concern because of the uncertain
      relevance and extrapolation of this finding to humans. In dogs, profound heart
      rate (HR) and mean arterial pressure (MAP) changes were considered surrogate
      markers for drug-induced vascular injury until the early 1990s when endothelin
      receptor antagonists (ETRA) did not significantly alter HR or MAP but induced
      identical lesions in the coronary arteries of dogs. Thus significant alterations
      in HR and MAP were found not to be a prerequisite for this lesion. Clinically,
      the potential for vascular injury coupled with the lack of an unequivocal non
      invasive diagnostic marker is an issue of concern to pharmaceutical companies and
      the regulatory authorities. Therefore, qualification and validation of biomarkers
      as diagnostic tools for drug-induced vascular injury would add great value to
      risk management and expedite the drug development process. This review focuses on
      the status, progress and future trends in vascular biology aimed at
      identification and development of diagnostic markers that are specific, sensitive
      and possess potential utility in both a pre-clinical and clinical setting.

PMID- 17192030
TI  - Cytokines as potential biomarkers of liver toxicity.
AB  - Several important drug classes show pre-clinical hepatotoxicity or, in some cases
      hepatotoxicity in man in Phase III/IV not predicted by pre-clinical studies. This
      hepatotoxicity is associated with death of the parenchyma by both necrosis and
      apoptosis. Recent data have implicated molecular mediators of the immune response
      such as tumor necrosis factor alpha (TNFalpha), interleukin 1beta(1L-1beta) and
      interleukin 6 (IL6) in acute and chronic liver damage. These cytokines networks
      have been implicated in mediating the hepatic response to xenobiotics as diverse
      as PPAR ligands, acetaminophen and phenobarbitone. Thus, pro-inflammatory
      cytokines such as TNFalpha, IL1 beta and IL6 are released into the bloodstream
      both from the liver and from distal sites during hepatic toxic injury. Probably
      due to differences in the responses of rodent and human hepatocytes to cytokines,
      some clinical hepatotoxicities are not predicted by rodent models. However, the
      cytokine changes implicated in this human hepatic cell death could be manifest in
      rodent models and thus could be detected at the molecular level. Here we review
      the role of cytokines in different types of drug-induced liver injury and discuss
      whether these cytokine fingerprints are potential biomarkers of so-called
      idiosyncratic human liver toxicity.

PMID- 17192031
TI  - The introduction of toxicogenomics; potential new markers of hepatotoxicity.

PMID- 17192033
TI  - The use of histologically defined specific biomarkers in drug development with
      special reference to the glutathione S-transferases.
AB  - Failure of drug candidates late in development is very expensive. This can be
      reduced by using more specific biomarkers of effect and toxicity during the
      preclinical and development testing. However, traditional toxicity tests have not
      been developed to study toxicology and so may lack sufficient sensitivity and
      specificity hence the search for new biomarkers using the many "-omics"
      technologies. Important aspects of useful biomarkers are that their origin is
      known and localised so that one knows what is being observed. Furthermore,
      biomarkers with a localised origin are less likely to be subject to background
      variation and have a wider dynamic range. This paper will discuss how using
      biomarkers with a known cellular origin, toxic effects can be found earlier and
      at lower doses of compound.

PMID- 17192032
TI  - Protein biomarkers of nephrotoxicity; a review and findings with cyclosporin A, a
      signal transduction kinase inhibitor and N-phenylanthranilic acid.
AB  - Biomarkers of nephrotoxicity range from plasma and urine biochemistry, enzymic
      assays for brush border and lysosomal markers plus new protein markers by
      immunoassay. Because of the complexity of the nephron and regional sensitivity to
      xenobiotics, it is important to co-localise sites of marker release with
      pathological lesions. Han Wistar rats were treated p.o.for up to 14 days with
      compounds causing selective nephrotoxicity. Compounds used were cyclosporin A ,a
      signal transduction inhibitor and N-phenylanthranylic acid (NPAA). Plasma and
      urine was collected for biochemistry and urinalysis (including proteomics and
      metabonomics) and at termination kidneys were fixed for standard H&E pathology
      and immunohistochemistry examinations for D28 k calbindin, calmodulin, phospho
      erk, Cox 1, Cox 2 and other markers. Cyclosporin A treatment caused injury to the
      thick ascending limb (TAL) of the nephron and was associated with a down
      regulation of calbindin protein expression in cortical distal tubules (mean score
      75% reduction) and TALs (21% reduction). Inhibition of signal transduction used p
      erk as a downstream marker of activity. P-erk was highly expressed in the
      collecting ducts and inhibition of signalling caused a 39% reduction in IHC
      score. There was no evidence of direct renal injury by there was a hypercalcaemia
      (9% increase) and hyperphosphataemia (24% increase) at 24 hrs post-dose and
      metastatic calcification by 7 days. NPAA treatment caused renal papillary
      necrosis in some treated rats (sometimes unilateral) with some secondary dilation
      of distal tubules. Unlike NSAID treatment, there was no evidence of Cox 1 or 2
      dysregulation on IHC and the Cox1 positive interstitial cells did not loose
      integrity before the onset of necrosis. There were a number of urinary proteomic
      and metabonomic alterations which are being characterised. The 3 model
      nephrotoxicants studied demonstrated the linkage of protein expression on IHC to
      nephron segment-specific sites as important for urinary biomarker validation and
      linkage to mechanisms.

PMID- 17192034
TI  - Inhibin B as a potential biomarker of testicular toxicity.
AB  - Inhibin B is a glycoprotein produced predominantly by Sertoli cells which
      regulates pituitary FSH release by a negative feedback loop. The regulation of
      inhibin B is complex with changes in the pattern of secretion occurring during
      development, and many factors such as FSH, testosterone, Sertoli cell
      proliferation and germ cell complement likely to contribute to overall
      production. Systemic inhibin B concentrations seem to reflect the extreme ends of
      spermatogenic status with high levels of inhibin B observed in normal, fertile
      individuals and lower levels of inhibin B in individuals with severe damage to
      the testis as a result of germ cell depletion. Inhibin B has proved valuable in
      epidemiological studies exploring male infertility with data showing that inhibin
      B combined with FSH measurements has a higher positive predictive value for
      detecting male infertility than either alone. Inhibin B is proposed as a
      potential biomarker of testicular toxicity in rodent toxicity studies to
      compliment traditional endpoints. In pharmaceutical development, inhibin B might
      allow better linkage between animal study results and subsequent monitoring of
      testicular function in clinical trials. An international, intercompany project
      has been initiated to evaluate the overall suitability and limitations of inhibin
      B as a biomarker of testicular toxicity.

PMID- 17192035
TI  - Biomarkers of reproductive toxicity.
AB  - A biomarker can be broadly defined as any biological index capable of being
      measured, which is associated with or indicative of a defined biological endpoint
      such as a developmental or disease stage. Identification and verification of
      anatomical, endocrine, cellular and molecular biomarkers is crucial for
      successful clinical diagnosis and treatment of toxicity and disease, as well as
      basic toxicological, epidemiological and other research. Various biomarkers of
      reproductive development and health have been identified, including those
      associated with pubertal development, adult reproductive health and pregnancy
      outcome. Herein we discuss those in situ biomarkers which have been more closely
      associated with toxicant action on the reproductive system. Biomarkers of
      toxicant exposure and susceptibility are addressed, but the majority of the
      review focuses on those biomarkers which may prove useful for determining current
      pathophysiological status or predicting future adverse outcomes. In males these
      are primarily associated with altered spermatogenesis and sperm parameters, and
      in females with altered endocrine function. We conclude that although few robust
      in situ biomarkers are currently available which are specific for toxicant
      exposure, susceptibility or effect in reproductive systems, there is expectation
      that post-genomic technologies offer a new paradigm for identifying and verifying
      such biomarkers as may exist.

PMID- 17192036
TI  - Early detection of cancer. Abstracts and proceedings of the National Cancer
      Institute's Early Detection Research Network Workshop and the Associate Program,
      June 13, 2004, Bethesda, Maryland, USA.

PMID- 17192037
TI  - Early detection markers in Pancreas Cancer.
AB  - The role of early detection in cancer has shown improved survival for certain
      cancers, including colon cancer, cervical cancer and breast cancer. The
      possibility for early detection of pancreatic cancer may be realized by an
      improved understanding of the histology and molecular genetics of precursor
      lesions and cancerous lesions in pancreatic cancer and the development of
      sensitive and specific screening tests (both invasive and non-invasive) to detect
      early pancreatic cancer. The NIH-NCI Early Detection Research Network (EDRN) in
      Pancreatic Cancer has been focussed on the development and validation of new
      biomarkers for the detection of early pancreatic cancer. This review will focus
      on our understanding of the histologic and molecular model of pancreatic
      carcinogenesis, current strategies and limitations of screening for pancreatic
      cancer and the development and validation of new biomarkers for the early
      detection of pancreatic cancer.

PMID- 17192038
TI  - Detection of a K-ras mutation in urine of patients with colorectal cancer.
AB  - We previously demonstrated that human urine contains small, 150 to 250 nucleotide
      sized, soluble DNA derived from the circulation, which may be useful in the
      detection of colorectal cancer. In this report we have determined the stability
      of DNA in urine and have found that the half-life time interval of this small,
      fragmented DNA is at least 4 hours post collection. We further compared, in a
      blinded study, the frequency of detecting mutated K-ras sequence in DNA isolated
      from plasma and urine derived from individuals who have either a colorectal
      carcinoma (CRC), or adenomatous polyps that contain a mutation in codon 12 of the
      K-ras proto-oncogene. There was an 83% concurrence of mutated DNA detected in
      urine and its corresponding disease tissue from the same individuals, when paired
      urine and tissue sections from 20 patients with either CRC or adenomatous polyps
      were analyzed for K-ras mutation. However, only a 56% concurrence was observed
      when the matched plasma specimens were tested from these 20 patients. These
      results suggest that urine might be a better resource for detecting K-ras
      mutation in circulating DNA.

PMID- 17192039
TI  - Early non-invasive diagnosis of cervical cancer: beyond Pap smears and human
      papilloma virus (HPV) testing.
AB  - Cervical cancer is a major gynecologic malignancy around the world. However,
      current diagnostic methods such as Pap smear and human papilloma virus (HPV)
      testing are insufficient for an early diagnosis of cervical cancer, follow-up on
      therapy efficacy or to identify the women who might progress to cervical cancer
      (only about 1-5% of the HPV-positive women will develop cervical cancer).
      Patients with atypical squamous cells of undetermined significance (ASC-US)
      clearly need a better screening test. Developing a non-invasive method for early
      diagnosis of cervical cancer is essential. Our in vitro and translational
      research data support the hypothesis that: 1. Squamous cell cervical cancer is
      related to specific upregulation of tissue and serum Insulin-like Growth Factor
      II levels (IGF-II; 100% sensitivity and 100% specificity). Serum IGF-I, but not
      IGF-II levels are elevated in other gynecological, breast, lung and prostate
      cancers. Serum IGF-II test helps in diagnosing cervical cancer as early as ASC-US
      or cervical intraepithelial neoplasia (CIN)-I and in monitoring therapy efficacy
      (p < 0.001 by Student's 't' test and Chi-square analysis). 2. Concomittant to
      increased serum IGF-II levels, IGF-Binding Protein 3 (IGF-BP3) levels are
      significantly decreased in persistent CIN and cervical cancer (p < 0.0001). As
      IGF-BP3 modulates IGF-II biological activity, significantly decreased serum IGF
      BP3 levels (levels normalize after therapy; p < 0.001) may indicate a poor
      prognosis. Similar to serum IGF-II, serum IGF-BP3 levels help monitoring therapy
      efficacy in cervical cancer and advanced CIN. Measurement of serum IGF-II levels
      will help in early diagnosis of cervical cancer and monitoring of therapy
      outcome. Serum IGF-BP3 in conjunction with IGF-II levels may help in predicting
      prognosis as well as monitoring therapy efficacy.

PMID- 17192040
TI  - CpG island hypermethylation profiling of lung cancer using restriction landmark
      genomic scanning (RLGS) analysis.
AB  - Lung cancer remains the leading cause of cancer related mortality, accounting for
      almost one-third of cancer deaths in men and one-fourth of cancer deaths in
      women; 160,440 lung cancer deaths are expected in 2004. Survival from lung cancer
      depends mainly upon the stage at presentation. As localized tumors generally do
      not cause symptoms, the disease is usually diagnosed in symptomatic patients at
      advanced stages when the prognosis is poor. As a result, the overall 5-year lung
      cancer survival rate is only 15%. It is well known that epigenetic alterations
      such as DNA methylation of CpG dinucleotides located in CpG islands within the
      regulatory (promoter) regions of genes are associated with transcriptional
      silencing in cancer. Promoter hypermethylation of critical pathway genes could
      identify potential biomarkers for lung cancer risk. Our goal for this study is to
      identify novel hypermethylated genes in lung cancer. We have investigated the
      methylation profiles of DNA samples from 14 paired lung tumor and adjacent normal
      tissues resected from the same individuals using restriction landmark genomic
      scanning (RLGS). We could assess the DNA methylation status of an average of
      2,012 CpG islands for each tumor. We identified 162 differentially methylated
      loci where CpG islands were hypermethylated in lung tumors but not in adjacent
      non-cancer tissues. Among 162 sites of differential DNA methylation, detected
      from at least one tumor/normal pair, 21 hypermethylated genes were identified
      that were not reported previously as hypermethylated in lung tumor tissue.

PMID- 17192041
TI  - Repair of the oxidative DNA damage 8-oxoguanine as a biomarker for lung cancer
      risk.
AB  - DNA repair has a major role in suppressing the rate of accumulation of mutations.
      Therefore, variations in DNA repair are likely to play an important role in
      determining cancer risk. While there is compelling evidence that defects in DNA
      repair cause high predisposition to several hereditary cancers, there is a
      paucity of data on the role of DNA repair in sporadic cancers. We present our
      approach of using functional DNA repair tests, rather than gene polymorphism, to
      study the potential of DNA repair enzymes to serve as biomarkers for lung cancer
      risk. We have previously developed a functional DNA repair blood test for the
      enzymatic repair of the oxidative DNA lesion 8-oxoguanine, and found that reduced
      OGG activity is a risk factor in non-small cell lung cancer. Moreover the
      combination of smoking and low OGG activity was associated with a greatly
      increased lung cancer risk (Paz-Elizur et al, JNCI 95 (2003) 1312-1319). The use
      of OGG activity as a potential biomarker for lung cancer risk is validated in
      collaboration with the M. D. Anderson Cancer Center, under the sponsorship of the
      Associate Members Program of the Early Detection Research Network (EDRN, NCI,
      NIH).

PMID- 17192043
TI  - The role of standards in the development and implementation of clinical
      laboratory tests: a domestic and global perspective.
AB  - In the field of clinical laboratory medicine, standardization is aimed at
      increasing the trueness and reliability of measured values. Standardization
      relies on the use of written standards, reference measurement procedures and
      reference materials. These are important tools for the design and validation of
      new tests, and for establishing the metrological traceability of diagnostic
      assays. Their use supports the translation of research technologies into new
      diagnostic assays and leads to more rapid advances in science and medicine, as
      well as improvements in the quality of patient care. The various standardization
      tools are described, as are the procedures by which written standards, reference
      procedures and reference materials are developed. Recent efforts to develop
      standards for use in the field of molecular diagnostics are discussed. The
      recognition of standardization tools by the FDA and other regulatory authorities
      is noted as evidence of their important role in ensuring the safety and
      performance of in vitro diagnostic devices.

PMID- 17192044
TI  - Standards and controls for genetic testing.
AB  - The majority of genetic tests done today are completely home brew assays. A few
      of the more common tests are based on ASR level reagents. To date the only
      genetic assays that are available as FDA-approved in vitro diagnostic (IVD) kits
      are for analysis of the Factor V (Leiden) and Factor II (promoter G to A)
      mutations associated with thrombophilia risk for assessment of cytochrome P450
      2D6 and 2C19 polymorphisms and for analysis of mutations in the CFTR gene. In
      this regard, the lab community has taken the lead in development of standards and
      controls for genetic tests. As genetic testing enters the mainstream, we expect
      to see more approvals of IVD kits, and the IVD manufacturing community will take
      a larger role in providing the control materials for these assays. Commercially
      run proficiency testing programs are only available for the most common genetic
      tests. All other tests must use approaches such as sample swapping between labs
      to fulfill this requirement.

PMID- 17192046
TI  - Developing a cell line standard for HER2/neu.
AB  - Advancements in medical genetics are resulting in the identification of key
      molecules in the pathways that lead to carcinogenesis. With these discoveries,
      drugs are developed that target a protein or block a particular molecular pathway
      with the potential to bring about disease regression. The HER2/neu tyrosine
      kinase receptor is one such target. Therapy based on the humanised monoclonal
      antibody, trastuzumab, targets HER-2/neu and inhibits the growth of HER2/neu
      overexpressing breast cancer cells. Assays for markers to HER2/neu are
      forerunners of many more predictive assays that are likely to enter the clinical
      arena in the near future, many of which will require quantitative analysis. In
      the field of tissue based assay systems controversies are well documented on the
      lack of reproducibility in the immunohistochemical analysis HER2/neu. The
      problems encountered to date lye with the difficulty in reliably standardising
      the immunohistochemical assay. One of the first steps in addressing this issue is
      to develop a standard reference material against which the 'variable' of assay
      sensitivity for HER2/neu can be accurately gauged. Work in the United States and
      Europe aimed at providing a standard reference material for HER2/neu has already
      commenced. Preliminary work conducted in Europe shows that development of a
      standard comprised of cell lines is feasible and when employed as part of an
      external quality assurance programme, results in significant improvement in the
      numbers of clinical laboratories achieving appropriate results. In the United
      States it has been proposed that two standards consisting of well characterized
      cell lines will be produced, one a National Institute of Standards and Technology
      (NIST)--certifiable standard, and the other a commercially developed standard for
      use in all HER2/neu testing. The aim is that this approach will act as a template
      for other important predictive markers of the future.

PMID- 17192045
TI  - Standards for autoantibody testing; addressing future needs for autoimmune
      disease and cancer diagnosis.
AB  - It is widely held that determination of increased levels of serum autoantibodies
      can play an important role in the diagnosis and, in some cases, management of
      many autoimmune diseases. It is also widely held that such testing is fraught
      with problems relating to accuracy and detection of clinically relevant
      autoantibodies. Attempts to standardize autoantibody testing by making available
      standard reference sera, have helped to some degree to improve the testing.
      Nevertheless, problems still exist and may be causing the delayed diagnosis of
      severely debilitating and sometimes fatal autoimmune diseases. This paper
      discusses current practice, as well as, possible new approaches intended to make
      more robust, autoantibody determinations in all fields of medicine.

PMID- 17192047
TI  - Standards for validation of cancer biomarkers.
AB  - As large scale genomics and proteomics efforts identify an increasingly complex
      list of biomarkers to identify human disease, populations predictive for that
      disease, and drug or other therapy responses for treatment, attention is needed
      in the research and development arena to bring initial discoveries to clinical
      utility. This article reviews the process of biomarker test verification and
      analytical validation, utilizing measurement standardization. Two such
      measurement programs are described in this manuscript: the identification of
      mutations in human mitochondrial DNA, and the measurement of telomerase activity
      in cancer. These model programs address the need for a standardized procedure
      outlining critical steps to assessing whether a biomarker assay should proceed to
      clinical validation, and to identify whether reference materials development is
      needed to establish measurement accuracy and sensitivity.

PMID- 17192049
TI  - Cytochrome p4501A1 gene variants as susceptibility marker for prostate cancer.
AB  - CYP1A1 activates environmental procarcinogens and catalyzes oxidative metabolism
      of estrogens and is likely to play an important role in the etiology of prostate
      cancer. To evaluate this phenomenon, the association between two single
      nucleotide polymorphisms (A to G transition in exon7 leading to amino acid
      substitution Ile462Val and T3801C at 3'UTR) of CYP1A1 gene in prostate cancer
      were analyzed in a case-control study of 100 individuals in South Indian
      population. The estimated relative risk was significantly high for individuals
      with w1/m1 genotype at 3'UTR of CYP1A1 gene (OR-4.64; 95%CI = 1.51-14.86; P <
      0.01) whereas the CYP1A1 Ile/Val genotype (w2/m2) on exon 7 was found to be
      associated with a decreased risk for prostate cancer (OR-0.17; 95%CI = 0.02-0.89;
      P=0.03). A Stratified analysis of the genotypes with age of onset and tumor grade
      showed the w1/m1 genotype to be significantly associated with an early age of
      onset; however the tumor grades did not have significant association with the
      variant genotypes. Thus the present study indicates that individuals with the
      variant w1/m1 genotype exhibit an increased risk while those with w2/m2 genotype
      exhibit a decreased risk for prostate cancer.

PMID- 17192048
TI  - Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies
      with tumor stage of colorectal adenocarcinoma.
AB  - Although decreased or lack of expression of Bcl-2 has been correlated with
      advanced tumor stage and shortened patient survival in colorectal cancer (CRC),
      its value in predicting the recurrence has not been well explored. Therefore, we
      assessed the usefulness of phenotypic expression of Bcl-2 in non-Hispanic
      Caucasian patients with CRCs in identifying risk of recurrence. Archival tissues
      of 92 Stage II and 66 Stage III primary CRCs were evaluated for
      immunohistochemical expression of Bcl-2. None of these patients received either
      pre- or post-surgical adjuvant therapies. Kaplan-Meier and Cox proportional
      hazards methods were used to estimate the rates of recurrence and survival
      according to Bcl-2 expression. Decreased expression of Bcl-2 was associated with
      an increased rate of recurrence in patients with Stage II CRCs (5-year log-rank
      test P=0.0015; Hazard Ratio (HR)=3.90, 95%C.I.:1.55-9.77) but not with Stage III
      CRCs (5-year log-rank test P=0.6058; HR=1.07, 95%C.I.:0.47-2.45) after adjusting
      for other demographic and clinicopathological features. Furthermore, decreased
      expression of Bcl-2 was an indicator of short survival in patients with Stage II
      CRCs but not with Stage III CRCs. Thus, decreased or lack of Bcl-2 expression in
      primary CRCs may serve as a molecular biomarker of high risk of recurrence for
      Caucasian patients with Stage II CRCs. These findings might be useful in
      identifying biologically aggressive phenotypes of Stage II CRCs, and may aid the
      oncologist in designing maximally appropriate therapeutic regimens.

PMID- 17192050
TI  - Multianalyte profiling of serum cytokines for detection of pancreatic cancer.
AB  - Early detection of pancreatic cancer might improve clinical outcome. Significant
      alterations in the levels of individual serum cytokines have been reported in
      pancreatic cancer. We hypothesized that a multicytokine panel could serve as
      biomarkers for pancreatic cancer. To evaluate the diagnostic utility of such a
      panel, we have utilized a novel multianalyte LabMAP profiling technology that
      allows simultaneous measurement of multiple markers. In this study, a panel of 31
      serological markers including cytokines, chemokines, growth and angiogenic
      factors in combination with CA 19-9 was analyzed in sera of pancreatic cancer
      patients, patients with chronic pancreatitis, and matched control healthy
      subjects. Statistical analysis identified a multicytokine panel that was able to
      distinguish pancreatic cancer from healthy controls with a sensitivity of 85.7%
      and specificity of 92.3%, which was superior to performance of CA 19-9 alone.
      Importantly, a multicytokine panel allowed the discrimination of pancreatic
      cancer from chronic pancreatitis with high sensitivity of 98% and specificity of
      96.4%. In conclusion, we demonstrated that analysis of multiple serum cytokines
      using a novel LabMAP technology is a promising approach for development of a
      diagnostic assay for pancreatic cancer.

PMID- 17192051
TI  - Down regulation of adhesion protein E-cadherin in Epstein-Barr virus infected
      nasopharyngeal carcinomas.
AB  - Nasopharyngeal carcinoma (NPC) is a unique tumour due to its aetiology, incidence
      pattern and its consistent association with Epstein-Barr virus (EBV). EBV encodes
      many viral proteins, which targets crucial cell cycle regulatory proteins.
      Cadherins are a family of transmembrane glycoproteins, which mediates Ca2+
      dependent intercellular adhesion. Epithelial (E)-cadherin is an important member
      of this family, which is expressed predominantly on the surface of epithelial
      cells. E-cadherin acts as an invasion/metastasis-suppressor gene, hence knowledge
      of the molecular mechanism that controls its expression or function is of primary
      importance in understanding the process of tumor invasion. Loss of E-cadherin
      function has been shown to potentiate tumor cell invasion and interestingly, a
      large number of invasive tumors do not involve mutation of E-cadherin, but rather
      down regulation of expression. Hence in this study, an attempt was made to
      evaluate the protein level expression pattern of E-cadherin in relation to viral
      involvement and to correlate it with other clinico-pathological parameters. We
      observed a significant down regulation of E-cadherin in NPC and its histological
      subsets, when compared to the controls (p<0.001). Expression of E-cadherin ranged
      from mild to moderate and none of the NPC showed intense expression. E-cadherin
      expression showed a significant down-regulation in NPC lesions with EBV infection
      (r=-0.436, p<0.001). The down regulation of E-cadherin observed in NPC is in line
      with the previous reports in E-cadherin expression in various cancers. The total
      lack of E-cadherin expression in neoplastic cells might be due to
      hypermethylation of E-cadherin promoter or its down regulation by cellular
      transcription repressor. Our study also shows a significant down regulation of E
      cadherin in the presence of EBV, which also might involve the cellular DNA
      methylation machinery.

PMID- 17192052
TI  - Proteomics analysis of stage-specific proteins expressed in human squamous cell
      lung carcinoma tissues.
AB  - There is a growing interest in applying proteomics to gain insight into the
      mechanism of tumorigenesis, develop new markers for molecular diagnosis and
      accelerate drug development. In an attempt to find new stage-specific tumor
      markers, patients suffering from squamous cell lung carcinomas (SQCLC) at
      different pathologic stages have been selected to achieve differential protein
      expression patterns. Two-dimensional polyacrylamide gel electrophoresis (2-DE)
      profiles of human SQCLC and normal tissue were compared. Differential protein
      spots were identified with peptide mass fingerprinting (PMF) based on matrix
      assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF
      MS) and database searching. A total of 63 unique proteins were identified in this
      experiment. Among them, peroxiredoxin 1 (PRDX1) expression level was
      significantly increased from stage I to III, and had a slight decrease at stage
      IV; whereas, a lasting decrease in the expression level of tropomyosins 3 (TPM3),
      was observed with the malignant progression from I stage to IV stage. These
      results provide further insight into malignant transformation in SQCLC and
      proteins may serve as new biomarkers for early diagnosis.

PMID- 17192053
TI  - Is urokinase gene 3'-UTR polymorphism associated with prostate cancer?
AB  - Urokinase gene is believed to play a key role in tissue degradation and cell
      migration under various normal and pathological conditions, including cancer
      invasion and metastasis. It may be responsible in the development of prostate
      cancer (CaP), although there is lack of genetic evidence. Our aim was to study
      single nucleotide polymorphism (C/T) in 3'-untranslated region to investigate the
      possibility. DNA was extracted from blood samples of 103 CaP patients and 107
      normal controls. Polymerase chain reaction (PCR) based restriction analysis was
      used to identify the C/T polymorphism of the urokinase gene. Significant
      difference in the frequency distribution of CT and TT genotypes in CaP patients
      as compared to normal was observed (p=0.04). Two folds risk for prostate cancer
      with T alleles in north Indian population was apparent. We also observed
      significant association for TT genotypes with higher Gleason score of tumors in
      CaP patients (p<0.05). A positive association was also evident in tobacco users
      having T alleles with risk of CaP. Our findings demonstrated a positive
      association of T allele of 3'UTR of urokinase gene with the risk of prostate
      cancer. We therefore hypothesize that C/T polymorphism may influence the etiology
      of CaP and is likely to become another new marker.

PMID- 17192054
TI  - Lynch syndrome (HNPCC) and microsatellite instability analysis guidelines.

PMID- 17192055
TI  - Ascending the learning curve--MSI testing experience of a six-laboratory
      consortium.
AB  - According to recently published guidelines, microsatellite instability (MSI)
      testing of colorectal cancers may be clinically indicated on a significant
      proportion of all colorectal tumors. To date, nothing has been published
      regarding the reproducibility of MSI testing between laboratories. We present MSI
      quality control activities experience of a six center multinational consortium,
      as laboratories developed competency with MSI testing and interpretation. The aim
      of this paper is to share lessons learned and to describe the final concordance
      rates in scoring MSI markers within this consortium.

PMID- 17192057
TI  - When does MMR loss occur during HNPCC progression?
AB  - Inactivation of DNA mismatch repair (MMR) is the hallmark of hereditary
      nonpolyposis colorectal cancer (HNPCC) and sporadic colorectal cancers with
      microsatellite instability (MSI+). MMR loss results in a markedly elevated
      mutation rate, and many MS mutations are found in MSI+ cancers. In theory, it is
      possible to estimate the interval between MMR loss and cancer removal by counting
      numbers of cancer MS mutations--the more MS mutations, the longer the intervals
      since MMR loss. Using this somatic molecular clock approach, MMR loss is
      estimated to precede transformation (clonal expansion) and likely occurs in
      normal appearing colon. Surprising, ages at MMR loss are more consistent with MMR
      loss as a relatively late event during progression to MSI+ cancer.

PMID- 17192056
TI  - The use of microsatellite instability, immunohistochemistry and other variables
      in determining the clinical significance of MLH1 and MSH2 unclassified variants
      in Lynch syndrome.
AB  - Missense changes constitute approximately 1/3 and 1/5 of all rare sequence
      constitutional variations identified in the MLH1 and MSH2 genes by mutation
      screening. They represent a challenge for the clinician and for the genetic
      counselor, who often cannot use them for the management of Lynch syndrome
      families. Several parameters can be evaluated to gain insight into the
      significance of such unclassified variants (UVs). These include analysis of
      microsatellite instability (MSI), immunohistochemistry of mismatch repair (MMR)
      proteins, segregation data, frequency of the variants in control samples,
      presence of other pathogenic mutations, and functional and mRNA analyses. While
      none of these variables can be used alone to predict the significance of UVs in a
      single case, combined evaluation can lead to clinically useful conclusions. This
      review reports available information on a sample of MLH1 and MSH2 missense UVs,
      for which MSI and immunohistochemical data could be retrieved from the
      literature. Currently, since MSI analysis is routinely performed as a diagnostic
      test for Lynch syndrome, tumor MSI status represents the most important factor
      for determining the pathogenicity of UVs in MMR genes.

PMID- 17192058
TI  - New aspects in molecular diagnosis of Lynch syndrome (HNPCC).
AB  - Colorectal carcinoma is one of the most common cancers that occurs in the human
      population, resulting in a mortality rate of more than 50%. Mismatch repair (MMR)
      defects are mostly manifested as high levels of microsatellite instability (MSI
      H); this occurs in approximately 19% of all colorectal cancers including a
      smaller, but high-risk subgroup that is represented by hereditary nonpolyposis
      colorectal cancer (HNPCC, Lynch syndrome). The aim of molecular diagnosis is to
      distinguish these familial cases from of the majority of sporadic unstable
      cancers. Here, we review the widespread MSI-H phenotype in various tumours,
      assessing the genetic, epigenetic and morphological differences to distinguish
      between sporadic and familial unstable colorectal cancers. The most important
      morphological feature is the presence of tumour-infiltrating lymphocytes (TILs),
      the presence of which is typical in MSI cancers. The main discriminators for
      HNPCC patients are family history, age at onset up to 60 years and MMR defects
      caused by germline mutations. This is in contrast to the discriminators for
      sporadic colorectal cancers, which include onset at any age, BRAF mutation
      presence and epigenetically MMR inactivation by extensive CpG-island methylation.
      This article presents a modified strategy for molecular diagnosis of HNPCC by
      selective inclusion of recently recognized characteristics of tumours. The clear
      identification of affected families can improve the strategy of early detection,
      therapy and prevention of colorectal cancers.

PMID- 17192060
TI  - Gene expression analysis of tumor infiltrating lymphocyte markers in endometrial
      cancers indicates no significant increases in those cases with microsatellite
      instability.
AB  - Microsatellite instability (MSI) is seen in many cancers and is the result of
      either a germline or somatic defect in the DNA mismatch repair system.
      Microsatellite instability is common in endometrial cancers occurring in about
      25% of cases with endometrioid histology. Tumor infiltrating lymphocytes (TIL)
      are more prominent in colorectal cancer cases with MSI. The presence of increased
      TIL is associated with increased survival in these colorectal cancers, and is
      suggested as one possible mechanism to explain the increased survival rates in
      colorectal cancer patients with MSI positive cancers. Some degree of evidence
      indicates that increased TIL is also predictive of increased survival in
      endometrial cancer. The relative levels and states of activation of TIL in
      endometrial cancers with and without MSI has not been explored. Our previous data
      indicates that global gene expression patterns from MSI and non-MSI endometrial
      cancers are distinct, however TIL markers were not over-represented on
      statistically relevant gene lists that distinguish these groups. We further
      examined these pre-existing microarray data by directly querying transcripts
      present in the T-cell gene ontology (GO) group. No significant differences were
      observed between MSI and microsatellite stable (MSS) groups. Finally we directly
      examined a set of T-cell marker transcripts previously utilized to define
      increased activated and cytotoxic TIL in MSI positive colorectal cancers. Whereas
      colorectal cancers with MSI have been previously demonstrated to contain higher
      ratios of CD8/CD3 message levels we observed no difference in endometrial
      cancers. In addition, levels of CD3 indicated no increases in TIL in MSI positive
      cases and 2 markers of activation, granzyme B and IL-2R were not different in MSI
      positive and negative cancers. These data indicate that significant differences
      in TIL derived transcripts do not occur between endometrioid endometrial cancers
      with and without microsatellite instability.

PMID- 17192061
TI  - Microsatellite instability in the development of DNA mismatch repair deficient
      tumors.
AB  - Microsatellites are highly abundant short repetitive sequences found in the
      genomes across different species. They have gained increasing interest in recent
      years because length alterations in several coding as well as non-coding
      microsatellites are associated with a variety of different disorders.
      Particularly, microsatellite mutations play an important role in tumorigenesis of
      DNA mismatch repair deficient tumors that account for up to a 15% of colorectal,
      endometrial, and various other cancers. The systematic analysis of the
      distribution and function of affected microsatellite sequences has facilitated to
      unravel important steps in the selection processes that drive tumorigenesis.
      Here, we review the role of microsatellite mutations in the development of
      cancers with DNA mismatch repair deficiency, outlining biostatistical approaches
      for the identification of MSI target genes with relevance to MSI associated
      carcinogenesis. Knowledge about the biological impact of microsatellite mutations
      in these genes will potentially help to develop modified clinical concepts for
      diagnosis, prevention, and treatment of microsatellite unstable human cancers.

PMID- 17192063
TI  - Validation of pharmacogenomic biomarker classifiers for treatment selection.
AB  - Physicians need improved tools for selecting treatments for individual patients.
      Many syndromes traditionally viewed as individual diseases are heterogeneous in
      molecular pathogenesis and treatment responsiveness. This results in treatment of
      many patients with ineffective drugs and leads to the conduct of large clinical
      trials to identify small average treatment benefits for heterogeneous groups of
      patients. New genomic and proteomic technologies provide powerful tools for the
      selection of patients likely to benefit from a therapeutic without unacceptable
      adverse events. In spite of the large literature on developing predictive
      biomarkers and on statistical methodology for analysis of high dimensional data,
      there is considerable uncertainty about the validation of biomarker based
      diagnostic classifiers for treatment selection. In this paper we attempt to
      clarify these issues and to provide guidance on the design of clinical trials for
      evaluating the clinical utility and robustness of pharmacogenomic classifiers.

PMID- 17192059
TI  - Chemotherapeutic implications in microsatellite unstable colorectal cancer.
AB  - Chemotherapy for colorectal cancer is currently offered to patients based on the
      stage of their cancer, and there is evidence to show an overall survival benefit
      with 5-fluorouracil-based (5-FU) therapy for patients with lymph node metastasis
      who receive it. The pathogenesis of colorectal cancer involves genomic
      instability, with about 15% of tumors demonstrating a form of genomic instability
      called high-frequency microsatellite instability (MSI-H) and due to loss of DNA
      mismatch repair function, and the remainder of colorectal tumors lacking MSI-H
      with retained DNA mismatch repair function and called microsatellite stable
      (MSS), with a large proportion of these tumors demonstrating another form of
      genomic instability called chromosomal instability. There is now evidence to show
      that the form of genomic instability that is present in a patient's colorectal
      cancer may predict a survival benefit from 5-FU. In particular, patients whose
      colorectal tumors have MSI-H do not gain a survival benefit with 5-FU as compared
      to patients with MSS tumors. In vitro evidence supports these findings, as MSI-H
      colon cancer cell lines are more resistant to 5-FU compared to MSS cell lines.
      More specifically, components of the DNA mismatch repair system have been shown
      to recognize and bind to 5-FU that becomes incorporated into DNA and which could
      be a trigger to induce cell death. The binding and subsequent cell death events
      would be absent in colorectal tumors with MSI-H, which have lost intact DNA
      mismatch repair function. These findings suggest that: (a) tumor cytotoxicity of
      5-FU is mediated by DNA mechanisms in addition to well-known RNA mechanisms, and
      (b) patients whose tumors demonstrate MSI-H may not benefit from 5-FU therapy.
      Future studies should include a better understanding of the cellular mechanisms
      of the DNA recognition of 5-FU, multi-centered prospective trials investigating
      the survival benefit of 5-FU based on genomic instability, and the investigation
      of alternative chemotherapeutic regimens for patients with MSI-H tumors to
      improve survival.

PMID- 17192064
TI  - Building and validating a prognostic index for biomarker studies.
AB  - An important aspect of modern cancer research is identifying molecular and
      genetic markers that predict an individual's risk of recurrence and response to
      treatment. Increasingly, a large number of biomarkers are included in studies,
      even though at most a small proportion of them will be prognostic. This article
      considers the selection and validation of prognostic biomarkers, and proposes a
      method for building and validating a prognostic index based on potentially many
      markers. We use simulation to show that our proposed method controls false
      positive rate while retaining reasonable power. The prognostic index gets its
      power from combining prognostic biomarkers. It can be very powerful even when
      there are few markers that are predictive.

PMID- 17192065
TI  - Genomic approach to biomarker identification and its recent applications.
AB  - This paper discusses selected activities, issues, and challenges in recent
      development of analytical methods and applications in biomarker identification
      and validation using state-of-the-art genomic approaches. Molecular profiling via
      genomics, proteomics, and metabonomics has opened new windows to study disease
      states and biological systems. It has also provided exciting opportunities for
      novel applications in clinical research as well as in drug discovery and
      development. In the past several years, we have witnessed enormous progress
      resulting particularly from gene expression profiling of mRNA or transcriptomics.
      After a brief review on technology advances in gene expression profiling using
      microarrays, I mainly discuss recent developments of the genomic approaches to
      biomarker identification and validation in two major types of applications. The
      first type involves examples in cancer diagnostics and prognostics based on tumor
      gene expression profiling, whereas the second type involves biomarker
      applications in drug discovery and development. The focus will be on analytical
      methods and algorithms that have been developed in recent years facilitating
      biomarker discovery and application by leveraging genome-wide expression profiles
      derived from microarrays. Technical issues in experimental design, data
      processing, error modeling, quality control, figures of merit for performance
      evaluation, and meta-analysis related to biomarker discovery and application are
      also discussed. A case study of disease outcome prognosis for breast cancer
      patients based on tumor expression pattern is presented before closing remarks.

PMID- 17192066
TI  - Scale-based normalization of spectral data.
AB  - Classification of data that arise as signals or images often requires a
      standardization step so that information extracted from biologically equivalent
      signals can be quantified for comparison across classes. Differences in global
      trend, total energy, high-frequency noise and/or local background can arise from
      variabilities due to instrumentation or conditions during data collection. This
      article considers some common ways in which such variation is adjusted for and
      introduces a generalization of the popular "standard normal variate"
      transformation. Based on a wavelet decomposition this generalization provides
      increased flexibility for normalizing spectral data affected by local background
      noise. Examples from three types of spectroscopy data illustrate the method and
      its properties.

PMID- 17192067
TI  - A measure of the performance of biomarkers for disease.
AB  - The statistical properties required for effective biomarkers for disease are
      examined. It is shown that an "effectiveness parameter" D can be calculated that
      summarises the performance of a given biomarker and can distinguish between
      effective and ineffective biomarkers. D can be readily calculated from published
      summaries of biomarker levels and provides a simpler alternative to the commonly
      used "Area under the Curve" statistic. The impact of within-individual and
      between-individual variation in biomarker levels is also evaluated. An approach
      to the choice of sample size for experiments to estimate D is described.

PMID- 17192068
TI  - Comparing adaptive and non-adaptive algorithms for cancer early detection with
      novel biomarkers.
AB  - It may be possible to reduce cancer mortality by monitoring the concentrations of
      serum biomarkers over time in men and women to detect their cancer early, when it
      is most curable. The simplest approach to using a biomarker for screening is to
      sequentially use fixed thresholds as a means to determine an abnormal test (e.g.,
      PSA exceeding 4 mg/ml, CA 125 exceeding 30 U/ml). Alternatives to the simplest
      single threshold (ST) rules include more sophisticated algorithms that make use
      of screening history that accumulates over time and determines abnormal tests
      using individualized reference ranges. Although in principle longitudinal
      algorithms should out perform fixed threshold rules, the actual benefit gained
      will depend on behavior of the biomarker, the screening algorithm, and the
      screening frequency. Little information has been available to help predict when
      conditions should compel the adoption of the more sophisticated algorithms and
      when conditions suggest the simpler algorithms should suffice, or indeed be
      preferred. In this manuscript we evaluate the conditions under which one should
      expect great benefit, and when one should not expect benefit, by comparing the
      ability of simple and complex algorithms to detect cancer early under a variety
      of biomarker behaviors and screening frequencies.

PMID- 17192070
TI  - One-pot procedure for diazo transfer and azide-alkyne cycloaddition: triazole
      linkages from amines.
AB  - [reaction: see text] A one-pot reaction for Cu(II)-catalyzed diazo transfer and
      Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (sometimes called click
      reaction) is reported. 1,4-Disubstituted 1,2,3-triazoles are obtained in
      excellent yields from a variety of readily available amines without the need for
      isolation of the azide intermediates. The reaction has a broad scope and is
      especially practical for the synthesis of multivalent structures because
      compounds substituted with multiple azides are potentially unstable.

PMID- 17192069
TI  - Non-invasive imaging of carcinogen-induced early neoplasia using ultrahigh
      resolution optical coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: Improved diagnostics capable of non-invasive detection
      of early stage carcinogenesis would benefit basic research, and potentially aid
      in clinical cancer diagnosis and management. The two-stage carcinogenesis
      protocol is widely used for studying the multi-stage nature of tumor development
      in mice and provides insight into tumor development in other animal models and
      humans. The objective of this study was to investigate the feasibility of non
      invasive optical coherence tomography (OCT) for in vivo imaging of
      microanatomical changes in the epidermis and dermis during early carcinogenesis
      using a mouse skin model. MATERIALS AND METHODS: 10 NIH mice were treated with
      DMBA and TPA following the well-established two-stage carcinogenesis protocol.
      OCT imaging of treated skin from live mice was performed at five time points
      (Week 4-8) after tumor initiation to reveal the structural changes in the
      epidermis and dermis associated with the earliest, premalignant stages of tumor
      development. OCT images were compared with histology findings. In addition, OCT
      signals were quantitatively analyzed to evaluate tissue optical property changes
      during early carcinogenesis. RESULTS: Early structural changes in the epidermis,
      dermis and hair follicles during carcinogenesis were clearly delineated in vivo
      using OCT. OCT images correlated well with histological findings. Quantitative
      OCT signal analysis revealed a statistically significant change in the extinction
      coefficient for untreated (40.5 +/- 17.0 mm(-1)) and treated (9.6 +/- 3.6 mm(-1))
      mouse epidermis (P < 0.005). The dermis extinction coefficient for the treated
      mouse skin (3.7 +/- 0.9 mm(-1)) was lower than the untreated one (4.7 +/- 1.6 mm(
      1)), but was not statistically significant (P > 0.10). Furthermore, the papilloma
      extinction coefficient (2.9 +/- 0.3 mm(-1)) was significantly lower than the
      extinction coefficient for the treated epidermis (P < 0.005) and dermis (P <
      0.01). CONCLUSION: OCT is a viable tool for assessing the earliest stages of
      carcinogenesis and has potential for early detection of neoplasia in skin, as
      well as in epithelial linings of other organs.

PMID- 17192071
TI  - Selective synthesis of (2Z,4E)-dienyl esters by ene-diene cross metathesis.
AB  - [reaction: see text] Cross metathesis of terminal alkenes with methyl (2Z,4E)
      hexadienoate and related dienyl esters provides substituted (2Z,4E)-dienyl esters
      in good yields. Small-scale reactions are effectively promoted by the standard
      second-generation Grubbs-Hoveyda catalyst (GH-II), while a new fluorous GH-II
      catalyst is used for separation and recovery in gram-scale reactions. The
      transformation is featured in a rapid synthesis of the bottom fragments of the
      potent anticancer agents (-)-dictyostatin and 6-epi-dictyostatin.

PMID- 17192072
TI  - Design and synthesis of redox stable analogues of sunflower trypsin inhibitors
      (SFTI-1) on solid support, potent inhibitors of matriptase.
AB  - [structure: see text] Matriptase is a member of the emerging class of type II
      transmembrane serine proteases. It was found that the sunflower trypsin inhibitor
      (SFTI-1), isolated from sunflower seeds, inhibits matriptase with a subnanomolar
      Ki of 0.92 nM. On the basis of this result, we designed and synthesized its
      proteolytically stable analogues, SFTI-2 and SFTI-3. SFTI-3 exhibited very good
      binding affinity to matriptase, and it was metabolically stable.

PMID- 17192073
TI  - Synthesis of a new (1R)-(-)-myrtenal-derived dioxadithiadodecacycle and its use
      as an efficient chiral auxiliary.
AB  - [reaction: see text] The new macrocycle 9 (>70% yield from hydroxythiol 10) was
      treated with several nucleophilic reagents (RMgX, RLi, and LiAlH4) affording
      carbinols 12a-j (80-96% yield, >99:1 dr). Oxidative hydrolysis of 12a,c,e,
      followed by LiAlH4 reduction of the resulting mixture, gave 16a,c,e in >95%
      ee,16c being a key precursor for the preparation of fungicide 17. The absolute
      configuration of 9 and 12j (Nu = H) was established by single-crystal X-ray
      diffraction analyses and chemical correlation.

PMID- 17192074
TI  - Atropisomers of meso-conjugated uracyl porphyrin derivatives and their assembling
      structures.
AB  - [reaction: see text] We have synthesized a 5,15 meso-substituted methyluracyl
      porphyrin derivative bearing 6-methyluracyl units directly at the meso positions.
      The atropisomerization was regulated by steric replusion between the methyl
      substituents. When the atropisomers were mixed with alkylated melamine as a
      complementary hydrogen-bonding unit, the hydrogen-bonded assemblies were analyzed
      by diffusion-ordered spectroscopy (DOSY) in solution, which clarified that the
      alphabeta isomer formed a face-to-face dimer, whereas the alphabeta isomer took a
      zigzag structure.

PMID- 17192075
TI  - C3-symmetric Ti(IV) triphenolate amino complexes as sulfoxidation catalysts with
      aqueous hydrogen peroxide.
AB  - [reaction: see text] The Ti(IV) complex 2c bearing a C3-symmetric triphenolate
      amine ligand is an air and moisture tolerant complex that efficiently catalyzes
      sulfoxidation reactions at room temperature without previous activation (catalyst
      loading down to 0.01%, TONs up to 8000, TOFs up to 1700 h-1, quantitative
      yields). Reactions were performed with aqueous hydrogen peroxide as oxidant,
      which adds value to the methodology from the environmental viewpoint.

PMID- 17192076
TI  - Solid-phase synthesis and CD spectroscopic investigations of novel beta-peptides
      from L-aspartic acid and beta-amino-L-alanine.
AB  - [structure: see text] A solid-phase synthesis method for the preparation of novel
      beta3- and beta2-peptides derived from l-aspartic acid and beta-amino-l-alanine,
      respectively, is described. The methodology allows independent buildup of the
      beta-peptide backbone and the introduction of sequential side chain
      substitutions. Representative peptides from the two classes, an amino-substituted
      beta3-hexapeptide and an acyl-substituted beta2-hexapeptide, have been prepared,
      and their solution conformation is studied by circular dichroism (CD)
      spectroscopy.

PMID- 17192077
TI  - CN-HMBC: a powerful NMR technique for the simultaneous detection of long-range
      1H,13C and 1H,15N connectivities.
AB  - [structure: see text] A new one-shot NMR experiment (CN-HMBC) is proposed for the
      simultaneous acquisition of 2D 1H,13C and 1H,15N HMBC spectra. Important
      sensitivity enhancements (up to 41% simultaneously for both 13C and 15N) or time
      savings (about 50%) can be achieved when compared to the separate acquisition of
      individual HMBC spectra. The experiment is highly recommended for the complete
      structural analysis and simultaneous chemical shift assignments of protonated and
      nonprotonated 13C and 15N resonances in nitrogen-containing organic compounds.

PMID- 17192078
TI  - Fluorescence turn on of coumarin derivatives by metal cations: a new signaling
      mechanism based on C=N isomerization.
AB  - [reaction: see text] A new sensing mechanism based on C=N isomerization, which
      shows a very significant fluorescence enhancement to the metal cations in a
      simple and efficient way, is demonstrated. A coumarin derivative (L) containing a
      C=N group was designed as an example for illustration. The free ligand L is
      almost nonfluorescent due to the isomerization of C=N double bond in the excited
      state. However, the solution of ligand shows about a 200-fold increase of
      fluorescence quantum yield (about 30%) upon addition of Zn(ClO4)2.

PMID- 17192079
TI  - Nonaromatic amidine derivatives as acylation catalysts.
AB  - [reaction: see text] Catalytic activity of nonaromatic bicyclic amidines and
      bicyclic isothioureas in acylation reactions was found to be remarkably dependent
      on the sizes of both rings. DBN and especially its thia-analogue (THTP) have been
      identified as highly active acylation catalysts.

PMID- 17192082
TI  - First chiral phosphoroamidite-phosphite ligands for highly enantioselective and
      versatile Pd-catalyzed asymmetric allylic substitution reactions.
AB  - [reaction: see text] A series of phosphite-phosphoroamidite ligands, derived from
      readily available d-xylose, has been successfully applied for the first time in
      the Pd-catalyzed allylic substitution of several substrates with different steric
      and electronic properties, with high enantioselectivities (ee's up to 98) and
      activities in standard conditions.

PMID- 17192080
TI  - Efficient synthesis of suitably protected beta-difluoroalanine and gamma
      difluorothreonine from L-ascorbic acid.
AB  - [reaction: see text] Fluorinated amino acids are useful building blocks for the
      preparation of biologically active peptides and peptidomimetics with increased
      metabolic stability. We report here the synthesis of two fluorinated amino acids,
      beta-difluoroalanine and gamma-difluorothreonine, as analogues of Ser and Thr,
      respectively. These compounds were suitably protected for Fmoc-based solid-phase
      peptide synthesis. Once incorporated into peptides, they may serve as alternative
      substrates or inhibitors of lantibiotic synthetases that posttranslationally
      dehydrate Ser and Thr residues to dehydroalanine and dehydrobutyrine,
      respectively.

PMID- 17192081
TI  - An efficient synthesis of epoxydiynes and a key fragment of neocarzinostatin
      chromophore.
AB  - [reaction: see text] A key structural feature of the Neocarzinostatin chromophore
      is a reactive epoxydiyne. We present here a new method for the preparation of
      epoxydiynes by the addition of an allenyl zinc bromide to a propargylic ketone.

PMID- 17192083
TI  - Air-induced anti-Markovnikov addition of secondary phosphine oxides and H
      phosphinates to alkenes.
AB  - [reaction: see text] Air (oxygen) induces the addition of secondary phosphine
      oxides and H-phosphinates to alkenes to selectively produce the corresponding
      anti-Markovnikov adducts in good to high yields. Mechanistic studies show that
      the addition probably proceeds via a radical chain mechanism.

PMID- 17192084
TI  - Simple and one-pot protocol for synthesis of indene-spiro-oxindoles involving
      tandem Prins and Friedel-Crafts reactions.
AB  - [reaction: see text] A simple and one-pot protocol for the synthesis of indene
      spiro-oxindole derivatives via TiCl4-mediated reaction between 1,1
      diarylethylenes and isatin derivatives involving construction of two carbon
      carbon bonds through tandem Prins and intramolecular Friedel-Crafts (PFC)
      reactions has been described. A plausible mechanism for this transformation is
      also presented.

PMID- 17192085
TI  - Selective formation of six-membered cyclic sulfones and sulfonates by C-H
      insertion.
AB  - [reaction: see text] Carbethoxy diazosulfones and sulfonates, easily available
      from corresponding sulfones and sulfonates, undergo C-H insertion with
      preferential formation of six membered cyclic sulfones and sulfonates.

PMID- 17192086
TI  - Total synthesis and biological evaluation of verticipyrone and analogues.
AB  - [reaction: see text] Total synthesis of verticipyrone, a novel NADH-fumarate
      reductase inhibitor, has been accomplished by a convergent approach using novel
      "Reverse Julia olefination" method. During total synthetic studies, we also
      prepared and evaluated several synthetic verticipyrone analogues, some of which
      exhibited more potent antiparasitic activity than the natural verticipyrone.

PMID- 17192087
TI  - Convenient synthetic approach to 2,4-disubstituted quinazolines.
AB  - [reaction: see text] 2,4-Dialkyl or aryl quinazolines have been prepared in three
      steps starting from easily available anilides. A photochemically induced Fries
      rearrangement of the anilides gave several ortho-aminoacylbenzene derivatives
      that were acylated at the NH2. These acylamides underwent rapid cyclization to
      2,4-disubstituted quinazolines (and benzoquinazolines) in the presence of
      ammonium formate under microwave activation. This procedure is compatible with
      different functional groups and allowed also the preparation of new quinazolines
      derived from naturally occurring amino acids.

PMID- 17192088
TI  - Iridium-catalyzed conversion of alcohols into amides via oximes.
AB  - [reaction: see text] The iridium catalyst [Ir(Cp*)Cl2]2 is effective for the
      rearrangement of oximes to furnish amides. The reaction has been combined with
      catalytic transfer hydrogenation between an alcohol and alkene to allow the
      conversion of alcohols into amides in a one-pot process.

PMID- 17192089
TI  - Stereoselective synthesis of the glycosidase inhibitor australine through a one
      pot, double-cyclization strategy.
AB  - [reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid
      australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The
      chiral starting materials were ketone 3, derived from L-erythrulose, and alpha
      alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was
      the highly stereoselective aldol reaction between 4 and a Z boron enolate derived
      from 3. Another key step was the one-pot construction of the bicyclic
      pyrrolizidine system by means of a three-step sequence of SN2 displacements
      induced by benzylamine on a trimesylate precursor.

PMID- 17192091
TI  - Application of the chiral bis(phosphine) monoxide ligand to catalytic
      enantioselective addition of dialkylzinc reagents to beta-nitroalkenes.
AB  - [reaction: see text] Me-DuPHOS monoxide is shown to be a very effective ligand in
      the enantioselective copper-catalyzed addition of dialkylzinc reagents to beta
      nitroalkenes providing access to chiral nitroalkanes. The major advantages of
      this process are high yields, broad and complementary substrate scope, and high
      enantioselectivities. The effect of achiral dummy ligands as an additive has also
      been documented.

PMID- 17192090
TI  - Singlet biradical character of phenalenyl-based Kekule hydrocarbon with
      naphthoquinoid structure.
AB  - [reaction: see text] A new Kekule polycyclic hydrocarbon with a singlet biradical
      index of 50% was synthesized. The singlet biradical character was assessed with
      UV and 1H-NMR spectroscopy, cyclic voltammetry, SQUID magnetic susceptibility
      measurement, and quantum chemical calculations.

PMID- 17192092
TI  - A bowl-shaped phosphine as a ligand in palladium-catalyzed Suzuki-Miyaura
      coupling of aryl chlorides: effect of the depth of the bowl.
AB  - [reaction: see text] Bowl-shaped phosphine ligands were found to be highly
      effective in Suzuki-Miyaura coupling of unactivated aryl chlorides, in which the
      depth of the bowl affected the catalytic activity considerably.

PMID- 17192093
TI  - Ladder distyrylbenzenes with silicon and chalcogen bridges: synthesis,
      structures, and properties.
AB  - [reaction: see text] A cascade-type anionic double cyclization of (o
      silylphenyl)(o-halophenyl)acetylenes via lithiation followed by treatment with
      elemental chalcogen produces silicon and chalcogen-bridged stilbenes. Based on
      this reaction, a series of silicon and sulfur- or silicon and selenium-bridged
      ladder distyrylbenzenes have been synthesized. Their chemical modification by
      oxidation, crystal structures, and photophysical properties are described.

PMID- 17192094
TI  - Highly enantioselective and diastereoselective 1,3-dipolar cycloaddition
      reactions between azomethine imines and 3-acryloyl-2-oxazolidinone catalyzed by
      binaphthyldiimine-Ni(II) complexes.
AB  - [reaction: see text] We have found the first example of high levels of asymmetric
      induction (97-74% ee) along with high diastereoselectivity (>99:1-64:36) in
      dipole-HOMO-/dipolarophile-LUMO-controlled asymmetric 1,3-dipolar cycloaddition
      reactions between fused azomethine imines and 3-acryloyl-2-oxazolidinone using a
      chiral BINIM-Ni(II) complex as a chiral Lewis acid catalyst.

PMID- 17192095
TI  - Synthesis of beta-lactam scaffolds for ditopic peptidomimetics.
AB  - [reaction: see text] Ring opening of alpha-substituted-alpha-methoxycarbonyl-N
      nosylaziridines provides a practical access to enantiopure alpha,alpha'
      disubstituted beta-lactam scaffolds, novel types of ditopic reverse turn
      surrogates. The procedure is general, short, and high yielding and starts from
      handy alpha-substituted serinates and alpha-amino acid derivatives.

PMID- 17192096
TI  - RuCl3/PPh3: an efficient combination for the preparation of chiral 1,3-anti-diols
      through catalytic hydrogenation.
AB  - [reaction: see text] An efficient economical alternative to the commonly used
      Evans' reagent for the diastereoselective reduction of beta-hydroxy ketones is
      reported. Thus, ruthenium-mediated hydrogenation of enantioenriched beta-hydroxy
      ketones using RuCl3 associated to achiral monophosphines allowed the preparation
      of a series of 1,3-anti-diols in good yields and with a high level of
      diastereoselectivity. A short screening of ligands pointed out PPh3 as the most
      effective phosphine, and PCy3 afforded the 1,3-diols with an unexpected moderate
      syn selectivity.

PMID- 17192097
TI  - Ligand-promoted dehydrogenation of alcohols catalyzed by Cp*Ir complexes. A new
      catalytic system for oxidant-free oxidation of alcohols.
AB  - [reaction: see text] An efficient catalytic system for oxidant-free oxidation of
      alcohols has been developed. A new Cp*Ir catalyst bearing a 2-hydroxypyridine
      ligand has been designed on the concept of "ligand-promoted dehydrogenation".
      Various secondary alcohols can be dehydrogenatively oxidized to ketones under
      neutral conditions with high turnover numbers by using the new Cp*Ir catalyst.

PMID- 17192098
TI  - Cope rearrangement versus a novel tandem retro-Diels-Alder-Diels-Alder reaction
      with role reversal.
AB  - [reaction: see text] A reinvestigation of the thermolysis of 4,4
      dibromotetracyclo[6.2.1.0(2,7).0(3,5)]undec-9-ene (2) affords diene 8 with a
      completely rearranged hydrocarbon skeleton via the isolable intermediate 4, along
      with cyclopentadiene and bromobenzene. DFT calculations show that the novel
      tandem retro-Diels-Alder-Diels-Alder reaction with role reversal is slightly less
      favored than the overall single-step Cope rearrangement.

PMID- 17192099
TI  - Lewis acid catalyzed rearrangement of vinylcyclopropenes for the construction of
      naphthalene and indene skeletons.
AB  - [reaction: see text] The choice of Lewis acid catalyst can result in dramatic
      differences in the chemoselectivity of the rearrangement reactions of
      vinylcyclopropenes. When BF3.OEt2 was used as the catalyst, naphthalenes were
      formed. However, when Cu(OTf)2 was used as the catalyst, indenes were obtained.

PMID- 17192100
TI  - Dual-mode semisquaraine-based sensor for selective detection of Hg2+ in a
      micellar medium.
AB  - [reaction: see text] A novel chemosensor based on semisquaraine dye (SSQ) for
      selective detection of Hg2+ is described. SSQ is obtained in quantitative yields
      from the reaction between squaric acid and 6-ethoxy-2-quinaldinium iodide. SSQ in
      combination with surfactant shows a dual chromogenic and fluorogenic response
      selectively toward Hg2+ as compared to Li+, Na+, K+, Ag+, Ca2+, Mg2+, Zn2+, Pb2+,
      Cd2+, Cu2+, and Fe3+ due to the soft acid nature and size of the mercuric ion.

PMID- 17192101
TI  - New macrocyclic compound as chiral shift reagent for carboxylic acids.
AB  - [structure: see text] We have prepared a novel chiral macrocyclic compound 3 from
      a C2-symmetric aminonaphthol in a high yield. Enantiomeric acids have large
      nonequivalent chemical shifts (up to 0.80 ppm) in the presence of 3 in 1H NMR
      (500 MHz) spectra. Quantitative analyses of a series of mandelic acids with
      different enantiomeric purities show that host 3 is an excellent chemical shift
      reagent for chiral carboxylic acids.

PMID- 17192103
TI  - Synthesis of silafluorenes by iridium-catalyzed [2 + 2 + 2] cycloaddition of
      silicon-bridged diynes with alkynes.
AB  - [reaction: see text] Silicon-bridged 1,6-diynes underwent [2 + 2 + 2]
      cycloaddition with alkynes in the presence of an iridium(I)-phosphine catalyst to
      afford densely substituted silafluorene derivatives. Extended silafluorene
      skeletons were constructed by the [2 + 2 + 2] cycloaddition of tetraynes.

PMID- 17192102
TI  - Two novel glycosidic triterpene alkaloids from the stem barks of Machilus
      yaoshansis.
AB  - [structure: see text] Two unusual glycosidic triterpene alkaloids,
      machilaminosides A (1) and B (2), have been isolated from the stem barks of
      Machilus yaoshansis. Their structures were elucidated by detailed spectroscopic
      analysis. A possible biogenetic origin of 1 and 2 mediated by the coupling of 2-O
      beta-D-glucopyranosyl-cucurbitacin I, respectively, with urea and adenosine was
      postulated. 1 and 2 showed nonselective cytotoxic activities against several
      human cancer cell lines as well as TNF-alpha secretion inhibitory activities.

PMID- 17192104
TI  - Benchtop monitoring of reaction progress via visual recognition with a handheld
      UV lamp: in situ monitoring of boronic acids in the Suzuki-Miyaura reaction.
AB  - [reaction: see text] Although boronic acids are widely used in metal-catalyzed
      reactions, it is difficult to assay their consumption. As such, we developed a
      reversible fluorescent sensor that is activated upon binding a boronic acid. The
      sensor can be used to monitor consumption of a boronic acid in Suzuki-Miyaura
      reactions. Importantly, only a standard handheld long-wave UV lamp (365 nm) is
      required and fluorescence is easily detectable with the naked eye without
      disturbing the reaction mixture.

PMID- 17192105
TI  - Total synthesis of (-)-blepharocalyxin D.
AB  - [reaction: see text] The Prins cyclization strategy was successfully applied in
      the total synthesis of (-)-blepharocalyxin D, a cytotoxic dimeric diarylheptanoid
      isolated from Alpinia blepharocalyx.

PMID- 17192107
TI  - Highly selective acetate aldol additions using mesityl-substituted chiral
      auxiliaries.
AB  - [reaction: see text] Highly diastereoselective acetate aldol additions using
      chlorotitanium enolates of mesityl-substituted N-acetyloxazolidinethione and N
      acetylthiazolidinethione auxiliaries are reported. These additions proceed in
      high yields and diastereoselectivities (93:7 to 98:2) for aliphatic, aromatic,
      and ,-unsaturated aldehydes. Double diastereoselective acetate aldol additions
      are also reported and are found to proceed in high yields and
      diastereoselectivities (90:10 to 97:3).

PMID- 17192106
TI  - Total synthesis of herbimycin A.
AB  - [structure: see text] Hsp90 has recently emerged as a promising biological target
      for treatment of cancer. Herbimycin A and other members of the benzoquinoid
      ansamycin class of natural products are known to inhibit Hsp90 activity. The
      total synthesis of herbimycin A was achieved from the commercially available
      Roche ester 1 by using allylmetals to control the stereogenic centers at C6, C7,
      C10, C11, and C12 and a ring-closing metathesis to control the (Z)-double bond of
      the (E,Z)-dienic moiety.

PMID- 17192108
TI  - Diastereoselective conjugate addition of organocuprates to 3,4-dimethyl-5,6
      dihydro-2(1H)-pyridinones. A concise synthesis of trans-3,4-dimethyl-4
      phenylpiperidines.
AB  - [reaction: see text] Conjugate addition of aryl or alkyl cuprates to 3,4-dimethyl
      5,6-dihydro-2(1H)-pyridinones led to diastereoisomerically pure 3,4,4
      trisubstituted 2-piperidinones in 39-78% yields. The yields and the
      diastereochemistry of piperidinones depended on both the N-protecting group and
      the organocuprate. Reduction then deprotection of the trans-3,4-dimethyl-4-phenyl
      product provided the corresponding piperidine, analogue of a key precursor of
      opioid receptor antagonists.

PMID- 17192109
TI  - Total synthesis of potential antitumor agent, (-)-dictyostatin.
AB  - [structure: see text] The potential antitumor agent (-)-dictyostatin has been
      synthesized utilizing Brown crotylboration to achieve eight of the eleven chiral
      centers. The yield for the 26-step longest sequence is approximately 4%. The C9
      C10 coupling is achieved via a stereoselective vinylzincate addition.

PMID- 17192110
TI  - Syntheses of conjugated pyrones for the enzymatic assay of lovastatin nonaketide
      synthase, an iterative polyketide synthase.
AB  - [reaction: see text] Lovastatin nonaketide synthase (LovB, LNKS) is an iterative
      type I polyketide synthase (PKS) from Aspergillus terreus that produces
      dihydromonacolin L (2), the biosynthetic precursor of lovastatin (1), from acetyl
      CoA, malonyl CoA, and S-adenosylmethionine (SAM) if the accessory protein LovC is
      present. In the absence of LovC, LNKS forms the conjugated pyrones 3 and 4 as
      truncated PKS products. Short syntheses of these pyrones provide material for the
      assay of LNKS activity by HPLC and radioisotope dilution analysis.

PMID- 17192111
TI  - Silver(I) triflate-catalyzed direct synthesis of N-PMP protected alpha
      aminopropargylphosphonates from terminal alkynes.
AB  - [reaction: see text] N-PMP protected alpha-aminopropargylphosphonates have been
      synthesized by using a silver(I) triflate-catalyzed one-pot three-component
      reaction of terminal alkynes, p-anisidine, and diethyl formylphosphonate hydrate.
      Good to excellent yields of the desired products may be obtained with a very
      simple procedure.

PMID- 17192113
TI  - Letter from the Commissioner's office at the US FDA.

PMID- 17192114
TI  - Rates and probabilities in economic modelling: transformation, translation and
      appropriate application.
AB  - Economic modelling is increasingly being used to evaluate the cost effectiveness
      of health technologies. One of the requirements for good practice in modelling is
      appropriate application of rates and probabilities. In spite of previous
      descriptions of appropriate use of rates and probabilities, confusions persist
      beyond a simple understanding of their definitions. The objective of this article
      is to provide a concise guide to understanding the issues surrounding the use of
      rates and probabilities reported in the literature in economic models, and an
      understanding of when and how to transform them appropriately. The article begins
      by defining rates and probabilities and shows the essential difference between
      the two measures. Appropriate conversions between rates and probabilities are
      discussed, and simple examples are provided to illustrate the techniques and
      pitfalls. How the transformed rates and probabilities may be used in economic
      models is then described and some recommendations are suggested.

PMID- 17192116
TI  - Cost effectiveness of a pharmacy-based coaching programme to improve adherence to
      antidepressants.
AB  - INTRODUCTION: The efficacy of antidepressants in the treatment of depression has
      been convincingly demonstrated in randomised trials. However, non-adherence to
      antidepressant treatment is common. OBJECTIVE: To evaluate, from a societal
      perspective, the cost effectiveness of a pharmacy-based intervention to improve
      adherence to antidepressant therapy in adult patients receiving treatment in
      primary care. METHODS: An economic evaluation was performed alongside a 6-month
      randomised controlled trial in The Netherlands. Patients who came to 19
      pharmacies with a new prescription for a non-tricyclic antidepressant, i.e. those
      who had not received any prescription for an antidepressant in the past 6 months,
      were invited to participate. They were then randomly allocated to education and
      coaching by the pharmacist or to usual care. The coaching programme consisted of
      three contacts with the pharmacist, with a mean duration of between 13 and 20
      minutes, and a take-home video reviewing important facts on depression and
      antidepressant treatment. The clinical outcome measures were adherence to
      antidepressant treatment measured using an electronic pill container (eDEM) and
      improvement in depressive symptoms measured using the Hopkins Symptom Checklist
      (SCL). Resource use was measured by means of questionnaires. The uncertainty
      around differences in costs and cost effectiveness between the treatment groups
      was evaluated using bootstrapping. RESULTS: Seventy patients were randomised to
      the intervention group and 81 to the usual care group; of these, 40 in the
      intervention group and 48 in the control group completed all of the follow-up
      questionnaires. There were no significant differences in adherence, improvements
      in the SCL depression mean item score and costs over 6 months between the two
      treatment groups. Mean total costs (2002 values) were 3275 euros in the
      intervention group and 2961 euros in the control group (mean difference 315
      euros; 95% CI -1922, 2416). The incremental cost-effectiveness ratio associated
      with the pharmacist intervention was 149 euros per 1% improvement in adherence
      and 2550 euros per point improvement in the SCL depression mean item score. Cost
      effectiveness planes and acceptability curves indicated that the pharmacist
      intervention was not likely to be cost effective compared with usual care.
      CONCLUSION: In patients starting treatment with antidepressants, there were no
      significant differences in adherence, severity of depression, costs and cost
      effectiveness between patients receiving coaching by a pharmacist and patients
      receiving usual care after 6 months. Considering the resources needed to
      implement an intervention like this in clinical practice, based on these results,
      the continuation of usual care is recommended.

PMID- 17192115
TI  - Reducing the societal burden of depression: a review of economic costs, quality
      of care and effects of treatment.
AB  - Depression is a highly prevalent condition that results in substantial functional
      impairment. Advocates have attempted in recent years to make the 'business case'
      for investing in quality improvement efforts in depression care, particularly in
      primary care settings. The business case suggests that the costs of depression
      treatment may be offset by gains in worker productivity and/or reductions in
      other healthcare spending. In this paper, we review the evidence in support of
      this argument for improving the quality of depression treatment. We examined the
      impact of depression on two of the primary drivers of the societal burden of
      depression: healthcare utilisation and worker productivity. Depression leads to
      higher healthcare utilisation and spending, most of which is not the result of
      depression treatment costs. Depression is also a leading cause of absenteeism and
      reduced productivity at work. It is clear that the economic burden of depression
      is substantial; however, critical gaps in the literature remain and need to be
      addressed. For instance, we do not know the economic burden of untreated and/or
      inappropriately treated versus appropriately treated depression. There remain
      considerable problems with access to and quality of depression treatment.
      Progress has been made in terms of access to care, but quality of care is seldom
      consistent with national treatment guidelines. A wide range of effective
      treatments and care programmes for depression are available, yet rigorously
      tested clinical models to improve depression care have not been widely adopted by
      healthcare systems. Barriers to improving depression care exist at the patient,
      healthcare provider, practice, plan and purchaser levels, and may be both
      economic and non-economic. Studies evaluating interventions to improve the
      quality of depression treatment have found that the cost per QALY associated with
      improved depression care ranges from a low of 2519 US dollars to a high of 49,500
      US dollars. We conclude from our review of the literature that effective
      treatment of depression is cost effective, but that evidence of a medical or
      productivity cost offset for depression treatment remains equivocal, and this
      points to the need for further research in this area.

PMID- 17192117
TI  - A lifetime modelled economic evaluation comparing pioglitazone and rosiglitazone
      for the treatment of type 2 diabetes mellitus in the UK.
AB  - INTRODUCTION: Adding pioglitazone or rosiglitazone to existing therapy are
      alternative treatment options for patients with type 2 diabetes mellitus who have
      insufficient glycaemic control while receiving the maximal tolerated dose of
      metformin monotherapy. Our objective was to develop a lifetime model of type 2
      diabetes mellitus and its sequelae in order to compare the costs and benefits of
      pioglitazone versus rosiglitazone in combination with metformin. METHODS: A
      decision-analytic model employing a first order Monte Carlo simulation of a
      Markov process was constructed. The model incorporated surrogate outcome measures
      from a large randomised controlled trial (RCT) [n = 802] that compared the
      glycaemic and lipid control of pioglitazone and rosiglitazone monotherapy. These
      efficacy data were used with a recently validated and peer-reviewed UKPDS (UK
      Prospective Diabetes Study) algorithm to simulate the progression of these
      surrogate outcomes to final health outcomes, including quality of life (QOL) and
      mortality, and to calculate the risks of diabetic complications and death. The
      model perspective was of the UK NHS and included direct healthcare costs only
      (pounds, 2004/5 values). Patient outcomes measured in the model included life
      expectancy (LE) and QALYs. The base-case analysis was run for 56-year-old male
      Caucasions with a haemoglobin A(1c) (HbA(1c)) of 7.57% and a body mass index of
      33.14 kg/m(2). RESULTS: Patients treated with pioglitazone experienced a
      reduction in the total cholesterol to high-density lipoprotein-cholesterol (TC :
      HDL-C) ratio of 0.34, whereas the TC : HDL-C ratio increased by 0.65 in those
      receiving rosiglitazone (p < 0.001). The HbA(1c) profile was similar between the
      treatment groups (p = 0.13), as were other known risk factors for diabetes
      complications. The lifetime healthcare costs per patient estimated by the model
      were 9585 pounds for pioglitazone and 10,299 pounds for rosiglitazone. Patients
      treated with pioglitazone had a discounted LE of 8.83 years versus 8.79 years for
      those treated with rosiglitazone. Patients treated with pioglitazone also gained
      additional QALYs (6.8070 vs 6.7686). With improved health outcomes and lower
      costs, treatment with pioglitazone dominated rosiglitazone treatment. CONCLUSION:
      Evidence from the only large head-to-head RCT comparing rosiglitazone and
      pioglitazone suggests that more favourable changes in serum lipid profiles in
      patients treated with pioglitazone translate into improved health outcomes in
      terms of reduced morbidity and mortality and greater gains in QOL. In addition,
      this analysis indicates that treatment with pioglitazone is associated with lower
      costs than rosiglitazone. Therefore, in the UK, adjunctive pioglitazone may
      represent a cost-effective treatment choice for patients with type 2 diabetes who
      have insufficient glycaemic control while receiving the maximal tolerated dose of
      metformin monotherapy.

PMID- 17192119
TI  - Time preferences for health in northern Tanzania: an empirical analysis of
      alternative discounting models.
AB  - AIM: The discounted utility (DU) model has dominated economic evaluation for
      almost 7 decades, despite the fact that important assumptions of the model are
      commonly found to be violated. This paper formally explores whether the key
      assumption of stationarity is violated in a sample of the general population of
      Northern Tanzania. Furthermore, three hyperbolic discounting models are fitted to
      the data, and whether they perform better than the DU model in predicting
      individuals' time preferences is tested using nonlinear least squares regression.
      METHOD: The data were collected from 450 households by trained enumerators. The
      individual data on time preferences were collected by structured interviews using
      an open-ended stated preference methodology. Respondents marked a rating scale to
      indicate the maximum number of days they would be willing to suffer a nonfatal
      disease if the outbreak of the disease could be delayed to a point further into
      the future. Households were randomised to answer questions framed to elicit
      either a private or social time preference. RESULTS: Hypothesis testing confirmed
      decreasing time aversion and a magnitude effect, suggesting that the DU model is
      inappropriate as a descriptive tool. When the DU model was compared with the
      three hyperbolic discounting models by analysing the discount factor using
      nonlinear least squares regression, the most important findings were that a
      variable for starting point was nonsignificant only for the Loewenstein and
      Prelec (L&P) and the Mazur models, and that people in this setting generally
      discounted future health far more than suggested by current discounting practice
      in economic evaluations. CONCLUSION: The time preferences of our sample are
      better represented by the L&P and the Mazur models (which allow relaxation of the
      stationarity assumption through a modification of the expression for the discount
      factor) and less well reflected by the Harvey (a modification of the L&P model
      that assigns more importance to the future than standard utility discounting) and
      DU models. This implies that, from the point of view of a consumer sovereignty
      friendly economist, the Mazur and the L&P models are preferable for discounting
      of future health in economic evaluations. However, from the point of view of
      other value bases for discounting the choice of discounting model is of less
      importance.

PMID- 17192118
TI  - Cost effectiveness of palivizumab for respiratory syncytial virus prophylaxis in
      high-risk children: a UK analysis.
AB  - OBJECTIVE: To assess the cost effectiveness of palivizumab (a preventative
      treatment against severe respiratory syncytial virus [RSV] infection) in children
      at high risk of hospitalisation, i.e. preterm infants < or = 35 weeks gestation,
      children with bronchopulmonary dysplasia (BPD) and children with congenital heart
      disease (CHD). METHODS: A decision tree model was developed employing data
      sources from the published literature, palivizumab clinical trials, official UK
      price/tariff lists and national population statistics. The comparator was no
      prophylaxis. The primary perspective of the study was that of the UK NHS. In a
      societal perspective scenario analysis, the future lost productivity of a child
      resulting from RSV-related mortality (indirect costs) was also included. The cost
      of administration of palivizumab, hospital care for RSV infections and the cost
      of asthma treatment were included. The analysis was based on a lifetime follow-up
      period in order to capture the impact of palivizumab on long-term morbidity and
      mortality resulting from an RSV infection. The primary efficacy outcome in the
      palivizumab clinical trials was the number of RSV hospitalisations avoided, which
      was extrapolated to effectiveness outcomes, i.e. number of life-years gained and
      number of QALYs. Costs and effects were discounted by 3.5%. RESULTS: In preterm
      infants and children with BPD, prophylaxis with palivizumab compared with no
      prophylaxis had an incremental cost-effectiveness ratio (ICER) of 7042
      pounds/QALY without discounting outcomes, increasing to 16,720 pounds/QALY after
      discounting. In babies with CHD, the use of palivizumab resulted in an ICER of
      2427 pounds/QALY without discounting outcomes and 6664 pounds/QALY after
      discounting. One-way sensitivity analyses and probabilistic sensitivity analyses
      confirmed the robustness of the model. A scenario analysis showed that the
      inclusion of indirect costs leads to further improvement in the cost
      effectiveness outcomes for palivizumab. CONCLUSION: This study suggests that
      palivizumab prophylaxis against severe RSV infection in children at high risk may
      be cost effective from the NHS perspective (vs no prophylaxis), and that the
      positive clinical and economic benefits may persist beyond one RSV season.

PMID- 17192120
TI  - Lipid rescue resuscitation from local anaesthetic cardiac toxicity.
AB  - Systemic local anaesthetic toxicity is a rare but potentially fatal complication
      of regional anaesthesia. This toxicity is due to inhibition of ionotropic and
      metabotropic cell signal systems and possibly mitochondrial metabolism. It is
      associated with CNS excitation and, in the extreme, refractory cardiac
      dysfunction and circulatory collapse. Infusion of lipid emulsion has been shown
      in animal models to reliably reverse otherwise intractable cardiac toxicity and
      the mechanism of lipid rescue is probably a combination of reduced tissue binding
      by re-established equilibrium in a plasma lipid phase and a beneficial energetic
      metabolic effect. Recent case reports have suggested the clinical efficacy of
      lipid infusion by the recovery of patients from intractable cardiac arrest.
      Future areas of investigation will focus on improved treatment regimes and better
      understanding of the mechanism of lipid rescue, which might allow superior
      alternative therapies, or treatment of other toxic events. An educational website
      has been established to help disseminate information about lipid emulsion therapy
      and to serve as a medium for physicians to share experiences or thoughts on the
      method and local anaesthetic toxicity.

PMID- 17192121
TI  - Manganese: pharmacokinetics and molecular mechanisms of brain uptake.
AB  - Manganese is an essential mineral that is found at low levels in virtually all
      diets. Manganese ingestion represents the principal route of human exposure,
      although inhalation also occurs, predominantly in occupational cohorts.
      Regardless of intake, animals generally maintain stable tissue manganese levels
      as a result of homeostatic mechanisms that tightly regulate the absorption and
      excretion of this metal. However, high-dose exposures are associated with
      increased tissue manganese levels, causing adverse neurological, reproductive and
      respiratory effects. In humans, manganese-induced neurotoxicity is associated
      with a motor dysfunction syndrome, commonly referred to as manganism or
      Parkinsonism, which is of paramount concern and is considered to be one of the
      most sensitive endpoints. This article focuses on the dosimetry of manganese with
      special focus on transport mechanisms of manganese into the CNS. It is not
      intended to be an exhaustive review of the manganese literature; rather it aims
      to provide a useful synopsis of contemporary studies from which the reader may
      progress to other research citations as desired. Specific emphasis is directed
      towards recent published literature on manganese transporters' systemic
      distribution of manganese upon inhalation exposure as well as the utility of
      magnetic resonance imaging in quantifying brain manganese distribution.

PMID- 17192122
TI  - Medical management of the traumatic consequences of civil unrest incidents:
      causation, clinical approaches, needs and advanced planning criteria.
AB  - In the context of this review, civil unrest is defined as disharmony, expressive
      dissatisfaction and/or disagreement between members of a community, which leads
      to a situation of competitive aggression that may find expression as disruption
      of organisation, conflicts, damage to property and injuries. Such a breakdown of
      harmonious relationships, which may result in property damage and human injuries
      that may be threatening to life, varies in magnitude from participation of a very
      few individuals up to the involvement of large crowds of people, which may evolve
      into a full-scale riot. It is the latter situation often involving demonstrators,
      opposing groups and law enforcement personnel that can result in multiple
      casualties and present a very significant challenge to the resources of local
      healthcare institutions. The causation of civil unrest incidents is
      multifactorial and has generic, specific and potentiating elements. With the
      current national and international societal, political and discriminatory
      problems, it is likely that civil unrest incidents on both small and large scales
      will continue to occur at a high and possibly increasing rate on a worldwide
      basis, and for these not infrequent incidents, the medical community should be in
      a state of informed preparation. The circumstances of civil unrest incidents are
      very variable with respect to causation, overall magnitude, frequency, timing,
      geographical location, numbers of persons involved, demographics of participants,
      influence of extremists, confrontation with opposing groups and control measures
      used by law enforcement agencies. Methods used by police and security forces for
      the control of civil unrest incidents, if advanced negotiations with organisers
      and verbal warnings have failed, fall basically into two categories: physical and
      chemical measures. Physical methods include restraint holds, truncheons, batons,
      mounted horses, projectiles (such as bean bags, plastic and rubber bullets),
      water cannons, tasers and (rarely) live ammunition. All of these physical
      measures are associated with pain and immobilisation, and there is a high
      potential for soft tissue and bone injuries. Some of the more severe physical
      methods, including plastic and rubber bullets, may cause lethal injuries. The
      basis for using chemicals in civil unrest incidents is that they cause
      distraction, transient harassment and incapacitation, temporary impairment of the
      conduct of coordinated tasks and cause a desire to vacate the area of unrest.
      Although screening smokes and malodors have sometimes been employed, the major
      group of chemicals used are peripheral chemosensory irritants (PCSIs), which
      reversibly interact with sensory nerve receptors in exposed skin and mucosal
      surfaces, resulting in the production of local uncomfortable sensations and
      associated reflexes. Major effects are on the eye, respiratory tract and (to a
      lesser degree) skin. Thus, the induced transient pain and discomfort in the eye,
      respiratory tract and skin, together with associated lacrimation, blepharospasm,
      rhinorrhoea, sialorrhoea, cough and breathing difficulties, produce temporary
      incapacitation and interference with the conduct of coordinated tasks, and form
      the basis for harassment of malefactors. Currently used peripheral chemosensory
      irritants are 1-chloroacetophenone, 2-chlorobenzylidene malononitrile,
      dibenz(b.f)-1,4-oxazepine, oleoresin capsicum and pelargonic acid vanillylamide.
      Depending on operational circumstances, irritants may be dispersed as a smoke,
      powder cloud, aerosol, vapour, or in solution; the mode of generation and
      dispersion of irritant can influence hazard. Brief acute exposure to chemosensory
      irritants produces effects that generally resolve within an hour, leaving no long
      term sequelae. However, sustained exposure to high concentrations may produce
      tissue injury, notably to the eye, respiratory tract and skin. With solutions of
      sensory irritants, other formulation constituents may enhance PCSI toxicity or
      introduce additional local and/or systemic toxicity. By the very circumstances of
      civil unrest incidents, injuries are inevitable, particularly when emotions are
      heightened and police and security forces have to resort to various chemical
      and/or physical means of control. Trauma may include slight to severe physical
      and/or chemical injuries, psychological problems and occasional deaths. Hospitals
      should be prepared for a wide range of casualties, and the fact that those
      seeking help will constitute a heterogeneous group, including wide age range,
      male, female, and individuals with pre-existing ill health. A major civil unrest
      incident necessitates that the local receiving hospital should be prepared and
      equipped for decontamination and triage processes. It is necessary to reassure
      patients who have been exposed to sensory irritants that the signs and symptoms
      are rapidly reversible, and do not result in long-term sequelae. With respect to
      chemical exposures, detailed evaluation should be given to possible ocular,
      cutaneous, respiratory and gastrointestinal effects. Also, exposure to
      chemosensory irritants results in transient increases in blood pressure,
      bradycardia and increased intraocular pressure. This indicates that those with
      cardiovascular diseases and glaucoma may be at increased risk for the development
      of complications. This article details the pharmacological, toxicological and
      clinical effects of chemicals used in civil disturbance control and discusses the
      management of contaminated individuals. Additionally, the potential for adverse
      effects from delivery systems and other physical restraint procedures is
      summarised. Due to the emergency and specialised circumstances and conditions of
      a civil unrest incident, there is a clear need for advanced planning by
      healthcare institutions in the event that such an incident occurs in their
      catchment area. This should include ensuring a good information base,
      preparations for medical and support staff readiness, and availability of
      required equipment and medications. Ideally, planning, administration and
      coordination should be undertaken at both local (regional) and central
      (governmental) centres. Regional centres should have responsibilities for
      education, training, ensuring facilities and staffing are appropriate, and that
      adequate equipment and medicines are available. There should be cooperative
      interactions and communications with local police and other emergency services.
      Centrally directed functions should include ensuring adequacy of the information
      base, coordinating activities and agreeing approaches between the regional
      centres, and periodic audits of regional centres with respect to the staffing,
      facility, equipment and training needs. Also, there is a need for most countries
      to introduce detailed guidelines and formal (regulatory) schemes for the
      assessment of the safety-in-use of chemicals and the delivery systems that are to
      be used against heterogeneous human populations for the control of civil unrest
      incidents. Such regulatory approval schemes should also cover advisory functions
      for safe use and any required restrictions.

PMID- 17192123
TI  - New syndromes in mushroom poisoning.
AB  - Several new mushroom poisoning syndromes have been described since the early
      1990s. In these syndromes, the onset of symptoms generally occurs >6 hours after
      ingestion. Treatment is mainly supportive. The syndrome induced by Amanita
      smithiana/proxima consists of acute tubulopathy, which appears earlier and does
      not have the same poor prognosis as the orellanine-induced syndrome. It has been
      described since 1992 in the US and Canada with A. smithiana; in France, Spain and
      Italy with A. proxima; and in Japan with A. pseudoporphyria. The responsible
      toxin is probably 2-amino-4,5-hexadienoic acid. The erythromelalgia syndrome has
      been described as early as the late 19th century in Japan and South Korea with
      Clitocybe acromelalga, and since 1996 in France and then Italy with C.
      amoenolens. Responsible toxins are probably acromelic acids identified in both
      species. Several cases of massive rhabdomyolysis have been reported since 1993 in
      France and 2001 in Poland after ingestion of large amounts of an edible and,
      until then, valuable species called Tricholoma equestre. These cases of
      rhabdomyolysis are associated with respiratory and cardiac (myocarditis)
      complications leading to death. Rhabdomyolysis with an apparently different
      mechanism was described in Taiwan in 2001 with Russula subnigricans. Finally,
      cases of encephalopathy were observed twice after ingestion of Hapalopilus
      rutilans in Germany in 1992 and Pleurocybella porrigens in Japan in 2004, where a
      convulsive encephalopathy outbreak was reported in patients with history of
      chronic renal failure.

PMID- 17192126
TI  - Intensive reduction of low-density lipoprotein-cholesterol: implications of
      recent trials.
AB  - Strong evidence supports the use of HMG-CoA reductase inhibitors (statins) for
      preventing ischemic events in a variety of clinical settings. Benefits have been
      documented in primary and secondary prevention, across a range of baseline
      cholesterol levels, in the young and old, and in patients with varying
      manifestations of cardiovascular disease. Epidemiologic evidence suggests that
      risk is associated with serum cholesterol in a continuous, graded fashion with no
      clear threshold below which further reductions in risk do not occur. In
      aggregate, the placebo-controlled statin trials strongly suggest that the
      magnitude of risk reduction is related to the degree of cholesterol lowering
      achieved. However, until recently, it was unknown whether intensified cholesterol
      lowering with higher doses of newer, more potent statins could bring further
      gains over a policy of moderate or conventional lipid lowering. This article
      summarizes the results of randomized trials comparing these two strategies in
      patients with a history of coronary artery disease.

PMID- 17192125
TI  - Effect of olmesartan medoxomil on atherosclerosis: clinical implications of the
      emerging evidence.
AB  - Angiotensin II is a potent vasoconstrictor and may also contribute to the
      progression of atherosclerosis. In atheromatous lesions located in human coronary
      and carotid arteries, angiotensin-converting enzyme and angiotensin II levels are
      significantly increased. Angiotensin II is known to have proinflammatory actions
      in vascular tissues, inducing inflammatory cytokines and oxidative stress. In
      particular, angiotensin II activates the potent cytoplasmic transcription factor
      nuclear factor-kappaB, which regulates leukocyte adhesion molecules, tumor
      necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1, and
      interleukin (IL)-6, and contributes to the recruitment of circulating mononuclear
      leukocytes to the arterial intima. Olmesartan medoxomil has one of the highest
      degrees of antihypertensive efficacy among the angiotensin II type 1 receptor
      antagonists. In the EUTOPIA (EUropean Trial on Olmesartan and Pravastatin in
      Inflammation and Atherosclerosis) trial, olmesartan medoxomil significantly
      reduced serum levels of high-sensitivity C-reactive protein, high-sensitivity
      TNFalpha, IL-6, and MCP-1, all of which are involved in promoting
      atherosclerosis. In a monkey atherosclerotic model, a 3-D intravascular
      ultrasound analysis of aortas showed that serum levels of MCP-1 and the degree of
      intimal hyperplasia were significantly lower after treatment with olmesartan
      medoxomil than before treatment. In VIOS (Vascular Improvement with Olmesartan
      Medoxomil Study), treatment with olmesartan medoxomil for 1 year, significantly
      reduced the wall-to-lumen ratio in arteries, whereas atenolol did not. Thus,
      olmesartan medoxomil, which rapidly reduces inflammatory markers, may have a
      beneficial antiatherosclerotic effect.

PMID- 17192127
TI  - Role of the renin-angiotensin-aldosterone system in diastolic heart failure:
      potential for pharmacologic intervention.
AB  - Congestive heart failure (CHF) is a major public health problem that results in
      tremendous economic burden. Diastolic heart failure (DHF) forms an important
      subset with increasing incidence and prevalence. There are widely variable
      estimates of the prevalence, ranging from 13% to 74% of all CHF presentations,
      and this is predominantly a result of a lack of uniform criteria for establishing
      a diagnosis. New developments in management of DHF have lagged behind those for
      systolic heart failure (SHF), for which numerous new therapeutic and device
      strategies have been instituted. The renin-angiotensin-aldosterone system (RAAS)
      plays an important role in the pathophysiology of both SHF as well as DHF. The
      beneficial role of ACE inhibitors as well as aldosterone antagonists in SHF has
      been well established. Because of its unique role of the RAAS in establishing
      fibrosis at a molecular level, RAAS blockade provides an opportunity to expand
      the therapeutic options for DHF. Thus far, in patients with primary DHF only the
      angiotensin receptor type 1 antagonist candesartan has been reported to decrease
      morbidity and probably mortality. Large, ongoing randomized trials including
      TOPCAT (Trial of Aldosterone Antagonist Therapy in Adults with Preserved Ejection
      Fraction Congestive Heart) and the I-PRESERVE (Irbesartan in Heart Failure with
      Preserved Systolic Function) are currently underway to establish the role of
      aldosterone antagonists in patients with DHF.

PMID- 17192128
TI  - The A-SACT (Achievement in Singapore of Cholesterol Targets) study in patients
      with coronary heart disease.
AB  - BACKGROUND: Cardiovascular disease remains a leading cause of death worldwide,
      with hypercholesterolemia being a major risk factor. Evidence-based consensus
      guidelines have recommended consideration of increasingly stringent cholesterol
      lowering goals, yet most patients do not meet these targets. Coronary heart
      disease (CHD) event and mortality rates and mean serum cholesterol levels have
      declined in Singapore in recent years; however, certain groups remain at elevated
      risk. OBJECTIVE: To determine (i) proportions of patients with CHD in Singapore
      who achieved goals for serum low-density lipoprotein-cholesterol (LDL-C); and
      (ii) factors influencing goal attainment. METHODS: A historical cohort study was
      conducted using records from the Singapore Cardiac Databank, a national registry
      of CHD patients. Serum LDL-C goal attainment was assessed in 5174 survivors of
      acute myocardial infarction or coronary revascularization (i.e. coronary artery
      bypass graft surgery or percutaneous coronary interventions), of whom 3811
      (73.7%) were at very high risk. RESULTS: At baseline, the mean patient age was
      60.3 years, mean serum value of total cholesterol was 228 mg/dL, and mean LDL-C
      was 163 mg/dL. Of all CHD patients, approximately 70% did not achieve a serum LDL
      C target of <100 mg/dL. Most patients receiving HMG-CoA reductase inhibitor
      (statin) regimens were treated initially with low- to medium-equipotency regimens
      and were never titrated to stronger regimens. The vast majority (approximately
      94%) of patients at very high risk did not achieve the stringent serum LDL-C
      target of <70 mg/dL. Patients receiving higher potency statins were significantly
      more likely to achieve LDL-C goals, whereas those with higher baseline LDL-C
      levels or Malaysian ethnicity were less likely to achieve LDL-C goals.
      CONCLUSIONS: Most CHD patients in the large group of Singapore residents with CHD
      in the present study did not achieve recommended LDL-C targets. A more effective
      disease-management approach, including patient education concerning lifestyle
      modification (e.g. diet, physical activity), efforts to enhance medication
      adherence, and more effective, well tolerated therapies such as high-equipotency
      or high-dose statins and statin combination regimens, may be needed to improve
      achievement of consensus cholesterol targets. This is the first study of
      cholesterol goal attainment in a large group of Southeast Asians and serves as a
      baseline for future evaluations in Asian populations.

PMID- 17192129
TI  - Bedtime administration of graded-release diltiazem in patients with inadequate BP
      control: a tolerability and efficacy study.
AB  - BACKGROUND: Achievement of target BP is a challenge in patients attending family
      practice. The long duration between administration of the last bedtime dose of
      antihypertensive medication and the physiologic early morning surge in BP makes
      it difficult to achieve satisfactory BP control. OBJECTIVE: To determine whether
      a new graded-release preparation of diltiazem (diltiazem XC), taken once daily at
      bedtime, will show an acceptable adverse-effect profile as well as improved BP
      control. STUDY DESIGN/SETTING: This is an open label, observational study in an
      ambulatory care setting. PATIENTS: 954 patients with mild to moderate
      hypertension and BP not at target levels were attended by 85 physicians. Group 1
      patients were receiving a diltiazem preparation and group 2 patients were not
      receiving any diltiazem preparation at baseline. INTERVENTION: Group 1 patients
      were given diltiazem XC at the same dose as the prestudy diltiazem. Treatment
      with diltiazem XC 180 mg was initiated in group 2 patients. Diltiazem XC was
      taken once daily at bedtime in both groups. MAIN OUTCOME MEASURE: The
      predetermined main outcome measure was the development of adverse events with
      diltiazem XC when changing or adding the study medication. The secondary outcome
      measure was the proportion of patients who achieved target BP levels. RESULTS:
      Moderate or severe adverse events occurred in 8.7% of patients. Although 21.8% of
      patients reported either new or worsening adverse events after starting diltiazem
      XC, the large majority of adverse events were mild in severity. The most frequent
      moderate or severe adverse events were headache (2.0%) and constipation (1.7%).
      More patients in group 2 reported adverse events compared with patients in group
      1. Target BP levels were achieved in 47.8% (95% CI 44.3, 51.3) of patients
      completing the 8- to 12-week treatment. No difference was found in the proportion
      of patients at target BP levels in groups 1 and 2. CONCLUSION: Diltiazem XC, when
      used in an ambulatory care setting for patients who have not achieved BP targets,
      shows an acceptable adverse-effect profile and results in an important
      improvement of BP control.

PMID- 17192130
TI  - The impact of baseline HR and BP on the tolerability of carvedilol in the
      elderly: the COLA (Carvedilol Open Label Assessment) II Study.
AB  - BACKGROUND: The COLA (Carvedilol Open Label Assessment) II Study prospectively
      evaluated the tolerability of carvedilol in 1030 patients >70 years of age with
      chronic heart failure (CHF). Tolerability, defined as patients receiving > or =3
      months of carvedilol and achieving a maintenance dosage > or =12.5 mg/day, was
      80%. In a multivariate analysis, advanced age, low DBP, left ventricular ejection
      fraction, obstructive airways disease, and a presence of diabetes mellitus were
      predictors of tolerability. The aim of this analysis was to evaluate further the
      relationship between baseline HR, SBP, DBP and tolerability in COLA II. METHODS:
      Baseline HR, SBP and DBP data were available in 1009 patients (98%). These data
      were analyzed as both continuous and categorical variables. For the latter
      analysis, the following categories were created: HR <70, 70 < or = HR <90, HR >
      or =90 bpm; SBP <120, 120 < or = SBP <160, SBP > or =160 mm Hg; DBP <70, 70 < or
      = DBP <90, DBP > or =90 mm Hg. RESULTS: Baseline HR did not differ between
      patients who tolerated carvedilol (T) and those who did not (non-T) [81 +/- 16 vs
      79 +/- 16 bpm]. However, SBP and DBP were significantly lower in the non-T versus
      the T group (131 +/- 20 vs 139 +/- 22 mm Hg for SBP [p < 0.001] and 77 +/- 11 vs
      81 +/- 12 mm Hg for DBP [p < 0.001]). Seventy-four percent of patients in the
      lowest category for baseline HR (<70 bpm tolerated carvedilol versus 82% and 79%
      of those in the higher categories (p = not significant). Seventy percent of
      patients in the lowest category of baseline SBP (<120 mm Hg) tolerated carvedilol
      versus 80% and 89% of those in the upper categories (p < 0.001). Similarly, 73%
      of patients in the lowest category for DBP (<70 mm Hg) tolerated carvedilol
      versus 78% and 87% of those in the upper categories (p < 0.005). CONCLUSIONS:
      Carvedilol is generally well tolerated by elderly patients with CHF, even in
      those with low baseline BP or HR. However, a low baseline SBP or DBP does
      identify patients who are less likely to tolerate the drug. Baseline HR does not
      appear to significantly affect tolerability in this population.

PMID- 17192131
TI  - Clopidogrel bisulfate: in ST-segment elevation myocardial infarction.
AB  - Clopidogrel bisulfate (hereafter, clopidogrel), a selective inhibitor of ADP
      induced platelet aggregation, is approved for the reduction of atherothrombotic
      events in patients with ST-segment elevation myocardial infarction (STEMI). In
      COMMIT/CCS-2, a well designed trial in 45,852 adult patients with STEMI, relative
      to aspirin alone, clopidogrel 75 mg/day plus aspirin treatment significantly
      reduced the risk of both coprimary endpoints: the composite endpoint of
      reinfarction, stroke, or death from any cause and the risk of death from any
      cause. Based on the findings of this trial, treating 1000 patients for
      approximately 2 weeks with clopidogrel is associated with nine fewer patient
      deaths, reinfarctions, or strokes during treatment. In CLARITY-TIMI 28, a well
      designed supportive study in 3491 adult patients with STEMI, clopidogrel plus
      aspirin reduced the odds that a composite primary endpoint event of an occluded
      infarct-related artery, recurrent myocardial infarction, or death from any cause
      would occur versus aspirin plus placebo. Clopidogrel treatment was generally well
      tolerated in these clinical trials, with no significant between-group difference
      in the rate of major bleeding in either trial. Experience in other patient
      populations (e.g. those with recent myocardial infarction, recent ischemic
      stroke, or established peripheral arterial disease) has shown that longer-term (<
      or =3 years) clopidogrel monotherapy is generally well tolerated.

PMID- 17192132
TI  - Clopidogrel bisulfate: in ST-segment elevation myocardial infarction: a viewpoint
      by Jeffrey W Moses.

PMID- 17192133
TI  - Clopidogrel bisulfate: in ST-segment elevation myocardial infarction: a viewpoint
      by Steven R Steinhubl.

PMID- 17192134
TI  - Clopidogrel bisulfate in st-segment elevation myocardial infarction: a viewpoint
      by Deepak L Bhatt.

PMID- 17192135
TI  - Ramipril: a review of its use in preventing cardiovascular outcomes in high-risk
      patients.
AB  - Ramipril is an oral, non-sulfhydryl ACE inhibitor thought to act in the renin
      angiotensin-aldosterone system to decrease vasopressor activity, aldosterone
      secretion, and bradykinin degradation. Ramipril is generally well tolerated and
      effective in the treatment of patients aged > or =55 years at high risk for the
      development of cardiovascular (CV) events, in whom the risk of myocardial
      infarction (MI), stroke, and CV death can be significantly reduced. The risk of
      these CV outcomes may also be reduced with ramipril therapy in various subgroups;
      these include patients with diabetes mellitus, peripheral arterial disease (PAD)
      or renal insufficiency, and women. Thus, ramipril, in addition to lifestyle
      interventions, should be considered an important therapy in the prevention of CV
      outcomes in high-risk patients.

PMID- 17192137
TI  - Introduction to special feature on self and identity.

PMID- 17192138
TI  - The mentalization-focused approach to self pathology.

PMID- 17192139
TI  - Ego identity and personality disorders.

PMID- 17192140
TI  - Toward a model of self pathology underlying personality disorders: narratives,
      metacognition, interpersonal cycles and decision-making processes.
AB  - If we want to explain the links between the various and heterogeneous elements-
      symptoms, dysfunctional forms of behavior and poor social functioning--making up
      personality disorders, we need model a self pathology that portrays dysfunctions,
      the links among them, and how their interactions maintain disorders over time. In
      our view, the most likely elements of self pathology are: a. problematic contents
      (thoughts and emotions)--experienced subjectively as states of mind and organized
      in the form of narratives; b. shortfalls in the ability, termed meta-cognition,
      to reflect on mental states, both of oneself and of others; c. pathogenic
      interpersonal schemas; and d. maladaptive decision-making processes. These
      elements get altered in the various personality disorders and interact to form
      typical pathological organizations. This article seeks to describe a model of
      self pathology in personality disorders and discuss its current scientific status
      based on a literature review that spans several disciplines. The model is
      illustrated with an example of how the pathogenic elements can interact to form
      personality disorder. Lastly, the limitations and advantages of the model are
      discussed.

PMID- 17192141
TI  - Disturbed sense of identity in borderline personality disorder.
AB  - Traditionally, personal identity is considered to be important for psychological
      health and adaptive functioning. Identity diffusion and other more severe forms
      of disturbance associated with personal identity are regarded as being essential
      parts of the borderline personality disorder. Moreover, disturbances in identity
      are seen as being part of the dynamic background for many of the symptoms and
      maladaptive behaviors found in borderline patients. It is argued, that the
      development of personal identity is intimately related to, and indeed dependent
      on, elements of modern culture, with significant cultural changes having affected
      the conditions under which human identity develops. Therefore, the identity
      diffusion seen in patients with borderline disorders must be understood in
      relation to not only the individual patient's personal history and inner
      structures but also contemporary late modern culture and social organization.

PMID- 17192142
TI  - The longitudinal study of personality disorders: history, design considerations,
      and initial findings.
AB  - The Longitudinal Study of Personality Disorders (LSPD) began in 1990 and it is
      the first NIMH-funded prospective multiwave longitudinal study of all DSM-defined
      personality disorders (PDs). The LSPD, now in its 16th year, has focused on
      several major issues including: (a) the epidemiology of the PDs; (b) the
      stability of individual differences and mean levels of PD features over time;
      (c); patterns of individual growth in PD features over time; (d) the development
      of a neurobehavioral model that links personality and personality disorder; (e)
      specification of those neurobehavioral systems predicting change in borderline
      personality disorder; and (f) illumination of simultaneous growth processes in
      neurobehavioral systems and PD. The LSPD possesses a number of methodological
      enhancements designed to increase the validity of the longitudinal findings such
      as a prospective multiwave design, use of a validated structured interview and
      well-known self-report instrument for Axis II assessments, double measurement of
      all major constructs under study, use of blinded interviewers for all interview
      Axis II assessments, and use of a community sample. The history and context in
      which the LSPD was developed is reviewed, methodological issues related to the
      study of PDs are discussed, primary LSPD findings to date are summarized, and
      future directions of the LSPD are introduced.

PMID- 17192143
TI  - Sexual sadism and sadistic personality disorder in sexual homicide.
AB  - Controversies exist about the diagnostic validity of sexual sadism and its
      relation to sadistic personality disorder in sex offenders. The aim of this study
      was to investigate which diagnostic, developmental, and criminal characteristics
      differentiate sexual sadistic from non-sadistic sexual homicide perpetrators.
      Psychiatric court reports on 166 men who had committed a sexual homicide were
      evaluated regarding psychiatric, sexual and criminal history. Sixty-one offenders
      (36.7%) with sexual sadism (SeSd) were compared with 105 (63.3%) offenders
      without this diagnosis (NSeSd). Besides the sexual sadistic symptoms, there were
      seven factors that discriminated best between the two groups (sexual masochism,
      sadistic personality disorder, isolation in childhood, multiple sexual homicide,
      previous rape, previous tendencies for similar behavior, and long duration of the
      homicidal act). Sexual sadism is connected with circumscribed other
      characteristics and has to be considered in risk assessment and treatment of sex
      offenders.

PMID- 17192146
TI  - Aminotransferase elevation in HIV/hepatitis B virus co-infected patients treated
      with two active hepatitis B virus drugs.
AB  - Discerning drug hepatotoxicity from viral hepatitis flares remains an ongoing
      problem unique to patients coinfected with HIV and hepatitis B (HBV). We present
      three such coinfected patients who have been on two anti-HBV agents, lamivudine
      and tenofovir disoproxil fumarate simultaneously, as part of highly active
      antiretroviral therapy (HAART). All three developed significant aminotransferase
      elevations 6-12 weeks after initiation of HAART despite being on two active HBV
      drugs. Two of the three patients were initially thought to have drug-related
      hepatotoxicity from HIV medications. It seems more likely that all three patients
      demonstrated hepatitis B reactivation of differing severity as the result of
      varying degrees of immune recovery. Distinguishing clearly between drug-related
      hepatotoxicity and hepatitis reactivation may be difficult but is important as
      their clinical management differs.

PMID- 17192147
TI  - Immune reconstitution inflammatory syndrome presenting as sinusitis with
      inflammatory pseudotumor in an HIV-infected patient: a case report and review of
      the literature.
AB  - Immune reconstitution inflammatory syndrome (IRIS) encompasses a variety of
      conditions that occur among HIV-infected patients in a temporal relationship with
      increases in CD4 cell count as a result of highly active antiretroviral therapy
      (HAART). Most conditions associated with IRIS are infectious. Malignancies, such
      as Kaposi's sarcoma, have also been reported. We report a case of sinusitis with
      presumptive inflammatory pseudotumor as a manifestation of IRIS that occurred 20
      weeks after the initiation of HAART.

PMID- 17192148
TI  - Reconstructive treatment for antiretroviral-associated facial lipoatrophy: a
      prospective study comparing autologous fat and synthetic substances.
AB  - Lipodystrophy is one of the foremost concerns among the HIV-positive population,
      and is often associated with psychosocial disorders. We evaluated the clinical
      efficacy of facial infiltrations with autologous fat, polylactic acid, and
      polyacrylamide gel using clinical inspection and facial photographs (ordinal
      scale). Additionally, we assessed the safety of the infiltration techniques and
      determined changes in patient satisfaction, emotional status, and quality of
      life. Evaluations were made at 48- and 96-week follow-up visits. This paper
      presents the 48- week follow-up results. The current analysis includes 138
      patients: 8, 25, and 105 in the fat, polylactic acid, and polyacrylamide gel
      groups, respectively. At baseline, almost 50% of the patients (67/138) presented
      grades 3 and 4 lipoatrophy, but at week 48 only 7.5% (7/93) remained in these
      advanced grades (no patients from the polyacrylamide group). A new round of
      infiltrations at week 48 was necessary in 35% (33/93) of patients (88%, 84%, and
      8% in the fat, polylactic, and polyacrylamide groups, respectively). No serious
      adverse events were detected with any of the substances. Patient satisfaction and
      quality of life improved significantly in all three groups. Infiltrations with
      autologous fat, polylactic acid, or polyacrylamide gel appear to be an effective
      and safe alternative to repair facial lipoatrophy, at least up to 48 weeks,
      significantly improving patient quality of life. Similar results were observed
      for all degrees of severity and between genders. Polyacrylamide gel provided the
      longest lasting benefits.

PMID- 17192149
TI  - High-Risk groups for late diagnosis of HIV infection: a need for rethinking
      testing policy in the general population.
AB  - The aim of the study was to identify high-risk groups and the determinants of
      late HIV diagnosis in France in the era of highly active antiretroviral therapy
      (HAART), from January 1996 to June 2005. Informations were collected from an
      electronic medical record of all HIV- 1-infected patients who sought care in six
      HIV reference centers in France, constituting a prospective multicentric cohort.
      Patients were defined as "late testers" if they had presented with either
      symptoms of clinical AIDS or a CD4 cell count less than 200/mm(3) during the year
      of diagnosis, as "nonlate" if their CD4 count was above 200, and as "unknown" if
      CD4 cell count in the year at the time of diagnosis was not documented. Among the
      4516 patients available for analysis, the percentage of late testing was 38% (n =
      1718) and decreased after 2003 (31.5% in 2004-2005). This percentage was higher
      in heterosexual men (48.2%) than in homosexual men (31.7%) or heterosexual women
      (32.6%) and was higher for patients older than 30. Heterosexual men living in a
      couple with children had a higher risk of late testing (odds ratio [OR] = 1.65,
      95% confidence interval [CI]: 1.03 to 2.66), while heterosexual women in a couple
      without children had a lower risk (OR = 0.46, 95% CI: 0.25 to 0.83). Among
      homosexual men, unemployment was associated with late testing (OR = 2.23, 95% CI:
      1.14 to 4.36). The proportion of late testing was still high. Groups classically
      identified as low risk for HIV infection, particularly heterosexual men in a
      couple with children, were found to be at high risk for late testing. It seems
      necessary to improve HIV testing policy in the heterosexual population.

PMID- 17192151
TI  - Systematic development of a self-help and motivational enhancement intervention
      to promote sexual health in HIV-positive men who have sex with men.
AB  - The objective of this study was to describe the application of a systematic
      process-Intervention Mapping-to developing a theory- and evidence-based
      intervention to promote sexual health in HIV-positive men who have sex with men
      (MSM). Intervention Mapping provides a framework that gives program planners a
      systematic method for decision-making in each phase of intervention development.
      In Step 1, we focused on the improvement of two health-promoting behaviors:
      satisfactory sexual functioning and safer sexual behavior. These behaviors were
      then linked with selected personal and external determinants, such as attitudes
      and social support, to produce a set of proximal program objectives. In Step 2,
      theoretical methods were identified to influence the proximal program objectives
      and were translated into practical strategies. Although theoretical methods were
      derived from various theories, self-regulation theory and a cognitive model of
      behavior change provided the main framework for selecting the intervention
      methods. The main strategies chosen were bibliotherapy (i.e., the use of written
      material to help people solve problems or change behavior) and motivational
      interviewing. In Step 3, the theoretical methods and practical strategies were
      applied in a program that comprised a self-help guide, a motivational
      interviewing session and a motivational interviewing telephone call, both
      delivered by specialist nurses in HIV treatment centers. In Step 4,
      implementation was anticipated by developing a linkage group to ensure
      involvement of program users in the planning process and conducting additional
      research to understand how to implement our program better. In Step 5, program
      evaluation was anticipated based on the planning process from the previous
      Intervention Mapping steps.

PMID- 17192150
TI  - Individual variability in barriers affecting people's decision to take HAART: a
      qualitative study identifying barriers to being on HAART.
AB  - The efficacy of highly active antiretroviral therapy (HAART) has been well
      documented, particularly among HIV-infected individuals with CD4 cell counts
      below 200/mm(3). Despite this, eligible individuals may continue to show some
      reluctance to use HAART. The present study explored the factors influencing
      patients' decision not to take HAART even though it was medically indicated
      according to current treatment guidelines and available at no cost to the
      individual. Fifteen eligible patients at an urban HIV clinic were interviewed
      regarding the barriers that affected their decision to decline HAART. Most
      participants had previous experience with antiretroviral therapy and though most
      believed that HAART was beneficial and felt confident that they could adhere to
      treatment, they did not feel HAART was the right choice for them at the present
      time. The Critical Incident Technique was used to identify and classify incidents
      participants identified as influencing their decision not to take HAART. A total
      of four categories emerged from the data: Medication Factors, Mood, Lack of
      Support, and Outcome Expectancies. The results of this study highlight the
      ambivalence individuals may feel when faced with the prospect of taking HAART.
      The extent to which each of these factors influenced their decision differed
      substantially among participants. Suggestions for possible clinical interventions
      that can be used to address these concerns are offered.

PMID- 17192152
TI  - The cost of care for patients with HIV from the provider economic perspective.
AB  - Health care costs for HIV infection are often reported from the economic
      perspective of third party payors and little data exist to show how total costs
      are distributed across specific health service categories. We used a
      retrospective cohort design to measure total medical costs for 1 year in a
      randomly selected sample of 280 patients treated for HIV infection at an urban
      health care facility. Inpatient and outpatient costs were measured from the
      economic perspective of the health care provider. Hospital costs included ward,
      ancillary, and procedure costs. Ambulatory included medications, primary and
      specialty care, case management, ancillary, and behavioral comorbidity treatment
      costs. The mean total was $20,114 per patient, of which $6,322 was for inpatient
      and $13,842 was for ambulatory services. Specific ambulatory costs were:
      medications, $9,257; primary, specialty and ancillary services, $3,470; and
      behavioral comorbidity treatment, $1,111. The mean annual outpatient ancillary
      cost was $841. Over 30% of the total service cost was for building and
      administrative overhead and approximately 25% of both hospital and clinic costs
      were for ancillary services. Independent predictors of high cost were CD4 counts,
      Medicaid eligibility, and behavorial comorbidities. Our outpatient costs were
      higher, with less variation than previously reported. Increasingly, there has
      been a shift of HIV care from hospital to ambulatory settings. We postulate that
      reimbursement rates have not captured the recent flourishing of ambulatory care.
      If reimbursement is not commensurate with outpatient advances, providers may be
      paradoxically underreimbursed for improving care.

PMID- 17192154
TI  - HIV increasing globally.

PMID- 17192153
TI  - Atripla approval in Europe.

PMID- 17192156
TI  - Antimicrobial susceptibility and staphylococcal chromosomal cassette mec type in
      community- and hospital-associated methicillin-resistant Staphylococcus aureus.
AB  - STUDY OBJECTIVE: To differentiate the characteristics of community-associated
      methicillin-resistant Staphylococcus aureus (MRSA) and hospital-associated MRSA
      isolates on the basis of their susceptibility profiles, induction of clindamycin
      resistance, and staphylococcal chromosomal cassette (SCC) mec types. DESIGN: In
      vitro molecular and susceptibility study of isolates obtained from December 2004
      January 2006 as part of a large, ongoing clinical study. SETTING: Level I trauma
      center in Detroit, Michigan. BACTERIAL STRAINS: Three hundred eight MRSA isolates
      randomly collected from patients; 130 were classified as community-associated,
      and 178 were classified hospital-associated by using definitions from the Centers
      for Disease Control and Prevention (CDC). INTERVENTION: Minimum inhibitory
      concentrations were tested on the basis of current guidelines from the Clinical
      and Laboratory Standards Institute. MEASUREMENTS AND MAIN RESULTS: All tested
      MRSA isolates were susceptible to daptomycin, linezolid, and vancomycin. In
      addition, community-associated MRSA isolates were significantly (all p < or =
      0.05) more susceptible to trimethoprim-sulfamethoxazole (99%), clindamycin (96%),
      and a fluoroquinolone (76%) than hospital-associated MRSA isolates. Inducible
      resistance to clindamycin was demonstrated in 8.4% of community-associated MRSA
      isolates versus 50% of hospital-associated MRSA isolates (p < or = 0.001). Of
      interest, 35% of the MRSA isolates collected from hospitalized patients (> 48 hrs
      after admission and according to the CDC definition) possessed SCCmec type IV.
      CONCLUSION: Overall, inducible clindamycin resistance occurred at significantly
      higher rates in the hospital-associated MRSA isolates, susceptibility differed
      significantly between community- and hospital-associated MRSA, and most of the
      hospital isolates contained SCCmec type IV.

PMID- 17192158
TI  - Effectiveness of statins in reducing the rate of severe sepsis: a retrospective
      evaluation.
AB  - STUDY OBJECTIVES: To determine whether use of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase inhibitors (statins) is associated with a reduced rate of severe
      sepsis, and to further characterize the effect of statins on the frequency of
      organ dysfunction in patients with severe sepsis. DESIGN: Retrospective cohort
      study. SETTING: University-associated teaching hospital. PATIENTS: Fifty-three
      patients admitted with sepsis; 16 were receiving statins and 37 were not
      receiving statins (controls) before admission. MEASUREMENTS AND MAIN RESULTS:
      Patients were identified by the International Classification of Diseases, Ninth
      Revision, Clinical Modification codes. Patient demographics, vital signs, and
      laboratory values were collected from their electronic medical records. The
      primary end point was rate of severe sepsis, defined in accordance with
      guidelines from the American College of Chest Physicians and the Society of
      Critical Care Medicine. Secondary end points were in-hospital mortality rate and
      rate of five categories of organ dysfunction (cardiovascular, renal, pulmonary,
      hematologic, and metabolic). Preadmission statin therapy, compared with no statin
      therapy, was associated with a 30% lower rate of severe sepsis (56% vs 86%,
      p<0.02). In-hospital mortality was not significantly different between groups
      (38% vs 49%, p=0.33); however, the rate of cardiovascular dysfunction, defined as
      hypotension requiring vasopressor therapy, was significantly lower in the statin
      group (38% vs 73%, p<0.02). No significant differences in the other organ
      dysfunction categories were noted between groups. CONCLUSION: Statins appear to
      prevent sepsis from becoming severe, most notably through prevention of sepsis
      induced hypotension. This potential role for statins in the prevention and
      treatment of severe sepsis should be further evaluated in a randomized controlled
      trial.

PMID- 17192157
TI  - Enteral glutamine supplementation in critically ill patients with burn injuries:
      a retrospective case-control evaluation.
AB  - STUDY OBJECTIVES: To evaluate the clinical application of enteral glutamine
      supplementation in critically ill patients and compare the frequency of
      nosocomial infections in these patients with a historical control group in a burn
      intensive care unit (BICU), and to assess lengths of stay in the hospital and
      BICU, mortality rates, and safety profile of glutamine. DESIGN: Retrospective
      case-control descriptive study. SETTING: A university-affiliated hospital BICU.
      PATIENTS: Seventeen patients receiving enteral glutamine supplementation and 15
      historical control patients who were admitted to the BICU for thermal burn
      injuries from January 1, 2001-September 30, 2004. MEASUREMENTS AND MAIN RESULTS:
      Data for patients receiving enteral glutamine supplementation were identified
      through the pharmacy database, and data for the control patients were identified
      through the BICU patient registry. No significant differences were noted in
      baseline characteristics or nutritional parameters and outcomes between the two
      groups. The mean daily dose and duration of glutamine were 0.52 g/kg and 21.6
      days, respectively. The mean number of infections/patient between the glutamine
      and control groups was similar (2.47 and 2.73, respectively) as was the number of
      gram-negative infections (1.29 and 1.20, respectively). Bloodstream infections
      occurred more frequently in the glutamine group (24 vs 8 patients, p=0.0006);
      however, cellulitis (4 vs 11, p=0.05) and pneumonia (9 vs 15, p=0.15) occurred
      less often. For the glutamine group versus control group, BICU length of stay
      (17.9 vs 15.3 days, p=NS), hospital length of stay (32.3 vs 26 days, p=NS), and
      mortality rates (0% vs 6.7%, p=NS) were similar between groups. No adverse events
      were attributed to glutamine supplementation. CONCLUSION: Enteral glutamine
      supplementation was not associated with a change in the cumulative rate of
      infectious complications compared with the control group, but this was attributed
      to more cases of bloodstream infections and fewer cases of pneumonia and
      cellulitis in the glutamine group. Large, prospective, randomized trials designed
      to detect small but clinically relevant outcomes are needed to definitively
      determine the effect of enteral glutamine supplementation in the BICU population.

PMID- 17192160
TI  - Discrepancies in identification of bleeding events after percutaneous coronary
      intervention.
AB  - STUDY OBJECTIVE: To evaluate the level of agreement between two sets of criteria,
      the Thrombolysis in Myocardial Infarction (TIMI) criteria and investigator
      developed criteria, for identifying bleeding events in patients who had undergone
      a percutaneous coronary intervention (PCI) and to measure length of hospital stay
      (LOS) as a surrogate marker of bleeding severity. DESIGN: Retrospective chart
      review. SETTING: Two university-affiliated medical centers. PATIENTS: Four
      hundred twenty-two consecutive patients who had undergone PCI from December 1,
      2001-June 30, 2002. MEASUREMENTS AND MAIN RESULTS: Data were collected on the
      number of bleeding events that occurred within 1 week after PCI (limited to one
      event/patient) and on LOS. Bleeding was assessed by TIMI criteria and by
      investigator-developed criteria. Bleeding according to TIMI criteria included
      intracranial hemorrhage, spontaneous hematuria or hematemesis, or decreases in
      hemoglobin level. Bleeding according to investigator-developed criteria included
      intracranial, retroperitoneal, intraocular, or clinically overt bleeding without
      a specified decrease in hemoglobin level. Agreement between criteria was assessed
      by means of the kappa statistic. Of the 422 patients, 23 (5%) experienced TIMI
      defined bleeding events and 229 (54%) investigator-defined bleeding events. A
      kappa value of 0.09 (95% confidence interval 0.06-0.13) indicated a poor level of
      agreement between the two sets of bleeding criteria. The effect of this
      discrepancy on LOS was 66 fewer days of care when TIMI criteria were applied
      versus investigator-developed criteria in the 206 patients who experienced
      bleeding events that met investigator criteria (total LOS 645 days) but not TIMI
      criteria (total LOS 579 days). CONCLUSION: Bleeding assessment with use of TIMI
      criteria versus investigator-developed criteria yielded discrepant bleeding event
      rates and LOS, making it difficult to accurately compare bleeding rates and
      consequences across clinical trials and in practice. Consensus bleeding criteria
      are needed for applications in clinical evaluations of antithrombotic agents.

PMID- 17192159
TI  - Risk of diabetes mellitus associated with atypical antipsychotic use among
      Medicaid patients with bipolar disorder: a nested case-control study.
AB  - STUDY OBJECTIVE: To quantify the risk of diabetes mellitus associated with
      atypical antipsychotics compared with conventional antipsychotics in managed care
      Medicaid patients with bipolar disorder. DESIGN: Retrospective nested case
      control study. DATA SOURCE: Integrated seven-state Medicaid managed care claims
      database from January 1, 1998-December 31, 2002. PATIENTS: Two hundred eighty
      three patients with diabetes (cases) and 1134 controls matched by age, sex, and
      the index date on which bipolar disorder was diagnosed. MEASUREMENTS AND MAIN
      RESULTS: Cases were defined as those having an International Classification of
      Diseases, Ninth Revision diagnosis of diabetes or those receiving treatment with
      antidiabetic drugs. Both case and control patients had at least a 3-month
      exposure to either conventional or atypical antipsychotic agents or three filled
      prescriptions related to treatment for bipolar disorder. Of the 283 cases, 139
      (49%) received atypical antipsychotics (olanzapine, risperidone, quetiapine,
      ziprasidone, and clozapine) and 133 (47%) were prescribed conventional
      antipsychotics. To compare the risk for new-onset diabetes associated with
      atypical versus conventional antipsychotics, we conducted a Cox proportional
      hazard regression, in which we controlled for age; sex; duration of bipolar
      disorder follow-up; use of lithium, anticonvulsants, antidepressants, and other
      drugs; and psychiatric and medical comorbidities. Compared with patients
      receiving conventional antipsychotics, the risk of diabetes was greatest among
      patients taking risperidone (hazard ratio [HR] 3.8, 95% confidence interval [CI]
      2.7-5.3), olanzapine (3.7, 95% CI 2.5-5.3), and quetiapine (2.5, 95% CI 1.4-4.3).
      The risk for developing diabetes was also associated with weight gain (HR 2.5,
      95% CI 1.9-3.4), hypertension (HR 1.6, 95% CI 1.2-2.2), and substance abuse (HR
      1.5, 95% CI 1.0-2.2). CONCLUSION: Olanzapine, risperidone, and quetiapine are all
      associated with development or exacerbation of diabetes mellitus in patients with
      bipolar disorder. When prescribing therapy for this patient population, metabolic
      complications such as diabetes, weight gain, and hypertension need to be
      considered.

PMID- 17192161
TI  - Pertussis resurgence: diagnosis, treatment, prevention, and beyond.
AB  - The introduction of routine vaccination against Bordetella pertussis more than a
      half century ago led to a drastic decline in the number of reported cases of
      pertussis. It was originally believed that lifelong immunity was afforded after
      vaccination. Unfortunately, this belief is flawed, as the highest number of
      pertussis cases since 1959 was reported in 2004. This significant increase has
      led to additional research on immunity, vaccination, and treatment of B.
      pertussis in all age groups. We performed a MEDLINE search of literature from
      1966-2006 to evaluate and review the existing data on immunity to and prevention
      or treatment of B. pertussis infections. Additional articles were identified from
      the bibliographies of reviewed literature. Numerous articles pertaining to these
      topics have been published recently. The most significant changes in the
      management of this infectious disease surround the new recommendations by the
      Advisory Committee on Immunization Practices for adult and adolescent
      immunizations to assist in preventing outbreaks of B. pertussis. The Centers for
      Disease Control and Prevention recently published guidelines updating the
      recommended pharmacologic agents for treatment or prevention of B. pertussis.
      Despite decades of successful vaccination programs, pertussis continues to be a
      problematic disease. Fortunately, data and vaccines are now available that make
      development of a pertussis booster vaccination campaign reasonable. However,
      until widespread compliance with such programs is achieved, clinicians need to
      maintain vigilance against pertussis.

PMID- 17192162
TI  - Micafungin: a new echinocandin antifungal.
AB  - The echinocandins represent the newest class of antifungals to combat infections
      caused by Candida sp. Micafungin is an echinocandin recently approved by the
      United States Food and Drug Administration. It is indicated in adults for
      esophageal candidiasis and prophylaxis against candidal infections in
      hematopoietic stem cell transplant recipients. Micafungin exhibits in vitro
      fungicidal activity against Candida sp, including fluconazole-resistant isolates.
      Its in vivo efficacy is comparable to that of fluconazole in the treatment of
      esophageal candidiasis and superior to that of fluconazole for prophylaxis of
      invasive candidal infections. Because it is not significantly metabolized by the
      cytochrome P450 3A system, micafungin is associated with few drug interactions.
      Micafungin does not require adjustment in patients with renal and/or hepatic
      impairment, and it has been shown to be well tolerated in both adult and
      pediatric patients. Its efficacy against Candida sp, coupled with its overall
      safety and drug interaction profiles, makes it an attractive option in the
      treatment against esophageal candidiasis and prophylaxis against invasive
      candidal infections.

PMID- 17192163
TI  - Historical review of carbamazepine for the treatment of bipolar disorder.
AB  - The management of bipolar disorder has seen significant evolution in terms of the
      number of treatment options now approved for both the acutely manic phase and the
      maintenance stages of the illness. In addition, new formulations of traditional
      agents are available for clinicians to use in their treatment approach. One such
      example is carbamazepine, which has approval by the United States Food and Drug
      Administration for the treatment of acute and mixed mania in an extended-release
      formulation that uses a three-bead delivery system. Although the parent compound
      has been available for decades, its approval for bipolar disorder is recent
      despite numerous clinical trials that have supported its use in both the acute
      and maintenance phases of bipolar disorder. Advantages of the new formulation
      include less fluctuation in plasma concentration and, in general, improved
      tolerability. However, issues remain with regard to cytochrome P450 drug-related
      interactions and the need for therapeutic drug monitoring (e.g., drug
      concentrations, epoxide metabolite concentrations, hematology, and liver function
      tests) as part of the treatment and monitoring process. We review the current
      body of literature describing the use of carbamazepine in bipolar disorder during
      both the acute and maintenance phases of the disorder, including trials of both
      monotherapy and combination therapy, as well as findings from trials that
      included patients with rapid cycling and mixed episodes.

PMID- 17192164
TI  - Therapeutic options for sleep-maintenance and sleep-onset insomnia.
AB  - Insomnia, defined as difficulty falling asleep, staying asleep, and/or
      experiencing restorative sleep with associated impairment or significant
      distress, is a common condition resulting in significant clinical and economic
      consequences. Many options are available to treat insomnia, to assist with either
      falling asleep (sleep onset) or maintaining sleep. We searched MEDLINE for
      articles published between January 1996 and January 2006, evaluated abstracts
      from recent professional meetings, and contacted the manufacturer of the most
      recent addition to the pharmacologic armamentarium for insomnia treatment
      (ramelteon) to gather information. Nonpharmacologic options include stimulus
      control, sleep hygiene education, sleep restriction, paradoxical intention,
      relaxation therapy, biofeedback, and cognitive behavioral therapy. Prescription
      and over-the-counter drug therapies include benzodiazepine and nonbenzodiazepine
      sedative-hypnotic agents; ramelteon, a melatonin receptor agonist; trazodone; and
      sedating antihistamines. Herbal and alternative preparations include melatonin
      and valerian. Before recommending any treatment, clinicians should consider
      patient-specific criteria such as age, medical history, and other drug use, as
      well as the underlying cause of the sleep disturbance. All pharmacotherapy should
      be used with appropriate caution, at minimum effective doses, and for minimum
      duration of time.

PMID- 17192165
TI  - Clarifying the role of rasburicase in tumor lysis syndrome.
AB  - Tumor lysis syndrome (TLS) is a complication of malignancies with high tumor cell
      proliferation, tumor burden, and chemosensitivity. It manifests with the release
      of intracellular components and results in hyperkalemia, hyperphosphatemia,
      hypocalcemia, and hyperuricemia. These biochemical abnormalities may lead to
      serious complications such as renal failure, cardiac dysrhythmias, and death.
      Rasburicase, a recombinant urate oxidase enzyme, is a new agent indicated in the
      treatment or prophylaxis of hyperuricemia in pediatric patients with cancer who
      are at high risk for TLS. We reviewed the evidence for treatment with this agent
      compared with standard therapy with allopurinol. Rasburicase may be considered
      for use in patients with hyperuricemia at presentation and in patients at high
      risk for TLS that would otherwise result in a delay in chemotherapy. However,
      randomized controlled trials are required to establish the comparative efficacy
      of rasburicase in the adult population. Preliminary evidence suggests that single
      dose or reduced-dose rasburicase may be effective in the prophylaxis and the
      treatment of hyperuricemia and TLS. However, to our knowledge, there is no
      evidence comparing clinically relevant outcomes such as acute renal failure or
      dialysis.

PMID- 17192166
TI  - Oncologic complications of human immunodeficiency virus infection: changing
      epidemiology, treatments, and special considerations in the era of highly active
      antiretroviral therapy.
AB  - Although highly active antiretroviral therapy (HAART) has revolutionized the
      treatment of human immunodeficiency virus (HIV)-positive patients, malignancies
      in the setting of HIV infection remain an appreciable problem. We evaluated the
      changing epidemiology of HIV-related malignancies, optimal neoplastics and their
      effect on viral dynamics, and evidence regarding drug interactions between
      chemotherapy and antiretrovirals. A MEDLINE search (January 1966-June 2006) was
      performed to identify clinical trials, review articles, and meta-analyses;
      abstracts from HIV conferences were also searched. Survival of patients with HIV
      related malignancies has substantially improved since the advent of HAART.
      Chemotherapy for malignancies in the HIV-positive population generally resembles
      that for the HIV-negative population, with trials revealing an elevated frequency
      of toxicities in HIV-positive patients. Studies of antineoplastics have shown no
      long-term adverse effects on viral dynamics in terms of immunologic or virologic
      HIV markers. Limited pharmacokinetic data with antineoplastics and
      antiretrovirals suggest possible changes in some pharmacokinetic parameters, but
      these results should be interpreted cautiously because of the small numbers of
      patients enrolled in the trials. Researchers also report an increased frequency
      of chemotherapy-related toxicities when HAART was coadministered with
      antineoplastics. This increase was likely due to impairment of cytochrome P450
      metabolism of antineoplastics by protease inhibitors. Because of the survival
      benefits of HAART, the integration of antiretrovirals with chemotherapy is now
      preferred for patients with HIV-related malignancies. However, because the
      metabolic pathways of many of these agents are similar, the effectiveness of
      antineoplastic therapy and its related toxicities should be vigilantly monitored
      in this patient population.

PMID- 17192167
TI  - Clinical importance of carbapenem hypersensitivity in patients with self-reported
      and documented penicillin allergy.
AB  - The risk of carbapenem hypersensitivity in patients with self-reported or
      documented penicillin allergy needs to be determined so that practitioners can
      make better-informed decisions regarding antibiotic therapy for this patient
      population. The risk of cross-reactivity between penicillin and carbapenem
      antibiotics initially was reported to approach 50%. Recent retrospective studies
      have suggested that the clinical risk of cross-hypersensitivity between these two
      drug classes is 9.2-11%, which is significantly lower than initially reported.
      Patients whose history of penicillin allergy is self-reported and is not type 1
      may be at moderate risk for hypersensitivity when treated with a carbapenem
      antibiotic. The risk of hypersensitivity appears to be higher in patients whose
      penicillin allergy was documented by a health care provider, those with several
      antibiotic allergies, and those with a positive penicillin skin test result or a
      history of type 1 penicillin hypersensitivity.

PMID- 17192168
TI  - Practical application of nonrandomized research to patient care: a case study of
      nesiritide.
AB  - Prospective, randomized clinical trials are the gold standard for establishing
      cause-and-effect relationships between therapeutic interventions and specific
      outcomes. Unfortunately, these types of studies are not always available to
      evaluate important clinical end points such as mortality. Meta-analyses and
      observational studies are often used in an attempt to fill the gap in the
      literature when no prospective, randomized trials exist to answer a research
      question. A rapid increase in the number of published meta-analyses and
      observational studies has occurred in recent years. In the absence of
      prospective, randomized studies, it is essential for the clinician to understand
      the important issues involved in interpreting these other types of studies. When
      evaluating a meta-analysis, the clinician should assess for several different
      forms of bias, clinical heterogeneity, and use of appropriate methodology. When
      evaluating an observational study, sources of bias and confounding should be
      identified. If the potential for confounding is present, the methods used to
      minimize the impact of confounders should be evaluated for appropriateness.
      Mortality associated with nesiritide in the treatment of acute decompensated
      heart failure is a contemporary example of the use of nonrandomized research to
      address a research question that is unanswered by prospective, randomized
      studies. We review the details of a recent meta-analysis and observational
      evaluation of mortality associated with nesiritide and discuss the issues that
      are important in critical evaluation of nonrandomized study designs.

PMID- 17192169
TI  - Subdural hematoma after a fall in an elderly patient taking high-dose omega-3
      fatty acids with warfarin and aspirin: case report and review of the literature.
AB  - The elderly population is at an increased risk for major bleeding, possibly due
      to increased sensitivity to anticoagulation, multiple comorbidities, and
      polypharmacy. Elderly patients receiving antiplatelet and anticoagulant therapy
      have an additional risk for bleeding. Omega-3 fatty acids, also known as fish
      oil, have been used for hyperlipidemia, coronary heart disease, hypertension, and
      other conditions. Some studies have demonstrated that consumption of fish oil
      concentrate, n-3 polyunsaturated fatty acid (n-3 PUFA), results in cardiovascular
      benefits that include reductions in mortality, sudden death, nonfatal myocardial
      infarction, and thrombotic stoke, as well as improvement in graft patency. The
      mechanism of action of n-3 PUFA is not completely understood, but a dual
      antiplatelet and anticoagulant effect has been proposed. Few data exist on
      whether or not fish oil can be used safely with other antiplatelet or
      anticoagulant drugs. We report the case of a patient who after a minor fall
      developed a subdural hematoma requiring craniotomy that likely was precipitated
      by concomitant use of high-dose omega-3 fatty acids 6 g/day with both aspirin and
      warfarin. These findings are important because of the wide availability of omega
      3 fatty acids and the propensity for use of complementary and alternative
      medicine in patients with cardiovascular disease who are already taking
      antiplatelet and/or anticoagulant agents. Judicious use of these combinations is
      advised, and pharmacists can play an important role in educating patients and
      other health care providers about the bleeding risks associated with combination
      therapy.

PMID- 17192170
TI  - Successful treatment of Klebsiella rhinoscleromatis bacteremia with levofloxacin.
AB  - A 71-year-old Caucasian woman was admitted to the hospital with right-sided
      weakness and slurred speech. Glioblastoma multiforme was diagnosed, and resection
      of the tumor was performed. During the patient's hospitalization, blood and urine
      cultures were obtained after her temperature rose to 103.3 degrees F. Four blood
      cultures revealed Klebsiella rhinoscleromatis sensitive to trimethoprim
      sulfamethoxazole, levofloxacin, cefazolin, gentamicin, and tetracycline, but
      resistant to ampicillin. The patient had no recent history of foreign travel.
      After a 3-week course with levofloxacin, the patient was afebrile, and repeat
      blood cultures were negative. To our knowledge, this was the first case of K.
      rhinoscleromatis bacteremia in the United States to be treated successfully with
      levofloxacin.

PMID- 17192171
TI  - Possible pentostatin-induced symptomatic hyponatremia.
AB  - Pentostatin is an adenosine deaminase inhibitor used in the treatment of hairy
      cell leukemia and T-cell lymphomas. A 27-year-old man with refractory cutaneous T
      cell lymphoma developed severe hyponatremia 3 days after completing his first
      cycle of pentostatin therapy. Shortly after hospital admission, he became
      disoriented and was admitted to the medical intensive care unit and treated with
      a combination of hypertonic saline, intravenous diuretics, and fluid restriction
      to reestablish normal sodium homeostasis. The mechanism by which pentostatin may
      have induced hyponatremia in this patient is unknown; clinical and laboratory
      findings represented both extrarenal sodium loss and syndrome of inappropriate
      antidiuretic hormone. Clinicians should be aware of the possible development of
      life-threatening symptomatic hyponatremia in patients receiving pentostatin.

PMID- 17192172
TI  - Illness-related behaviour and utilization of oral health services among adult
      city-dwellers in Burkina Faso: evidence from a household survey.
AB  - BACKGROUND: In sub-Saharan Africa, the availability and accessibility of oral
      health services are seriously constrained and the provision of essential oral
      care is limited. Reports from the region show a very low utilization of oral
      health care services, and visits to dental-care facilities are mostly undertaken
      for symptomatic reasons. The objectives of the present study were to describe the
      prevalence of oral symptoms among adults in Ouagadougou, capital city of Burkina
      Faso and the use of oral health services and self-medication in response to these
      symptoms and to measure the associations between predisposing, enabling and needs
      factors and decisions to seek oral health care. METHODS: The conceptual design of
      the study was derived from both the Andersen-Newman model of health care
      utilization and the conceptual framework of the WHO International Collaborative
      Study of Oral Health Outcomes. Data were obtained by two-stage stratified
      sampling through four areas representative of different stages of urbanization of
      Ouagadougou. The final study population comprised 3030 adults aged 15 years or
      over and the response rate was 65%. RESULTS: Overall, 28% of the respondents had
      experienced an oral health problem during the past 12 months; a high proportion
      (62%) reported pain or acute discomfort affecting daily life. In response to
      symptoms, only 28% used oral health facilities, 48% used self-medication and 24%
      sought no treatment at all. Multivariate analyses revealed that several socio
      economic and socio-cultural factors such as religious affiliation, material
      living conditions and participation in a social network were significantly
      associated with the use of oral health care services by adults who had
      experienced oral health problems during the previous year. CONCLUSION: The
      proportion of people who have obtained oral health care is alarmingly low in
      Ouagadougou and self-medication appears to be an important alternative source of
      care for adult city-dwellers. Decision-makers in sub-Saharan countries must seek
      to ensure that access to essential oral health care is improved.

PMID- 17192173
TI  - The use of a pre-operative scoring system for the prediction of
      phacoemulsification case difficulty and the selection of appropriate cases to be
      performed by trainees.
AB  - BACKGROUND: To establish whether a previously validated scoring system (Habib)
      for the prediction of risk or likelihood of posterior capsule rupture during
      phacoemulsification surgery could be used to: 1. Predict the difficulty of a
      phacoemulsification case, and 2. Select appropriate phacoemulsification cases for
      trainees. METHODS: The study sample was consecutive phacoemulsification cases
      undertaken by senior surgeons at a single ophthalmic unit over a three-week
      period (170 cases). Each case was scored using a potential difficulty scoring
      system. Immediately post-operatively, each case was given two scores by the
      operating surgeon (who was masked with regard to the potential complication
      score). The first score indicated the perceived difficulty of the case, and the
      second score, the degree of experience that they thought a trainee would require
      in order to have performed the same case without complication. RESULTS: Using
      Cuzick's non-parametric test for trend, there was evidence for a trend of
      increasing perceived difficulty with increasing potential difficulty score (p =
      0.05), and of increasing experience required with increasing potential difficulty
      score (p < 0.001) CONCLUSION: The authors advocate that Habib's potential
      difficulty scoring system can be used to inform the surgeon of the likely
      difficulty of a phacoemulsification case and to aid selection of appropriate
      cases for trainees prior to surgery.

PMID- 17192174
TI  - A modified McCabe score for stratification of patients after intensive care unit
      discharge: the Sabadell score.
AB  - INTRODUCTION: Mortality in the ward after an intensive care unit (ICU) stay is
      considered a quality parameter, and is described as a source of avoidable
      mortality. Additionally, the attending intensivist frequently anticipates fatal
      outcome after ICU discharge. Our objective was to test the ability of a new score
      to stratify patients according to ward mortality after ICU discharge. METHODS: A
      prospective cohort study was performed in the general ICU of a university
      affiliated hospital. In 2003 and 2004 we prospectively recorded the attending
      intensivist's subjective prognosis at ICU discharge about the hospital outcome
      for each patient admitted to the ICU (the Sabadell score), which was later
      compared with the real hospital outcome. RESULTS: We studied 1,521 patients with
      a mean age of 60.2 +/- 17.8 years. The median (25-75% percentile) ICU stay was
      five (three to nine) days. The ICU mortality was 23.8%, with 1,156 patients being
      discharged to the ward. Post-ICU ward mortality was 9.6%, mainly observed in
      patients with a Sabadell score of 3 (81.3%) or a score of 2 (41.1%), whereas
      lower mortality was observed in patients scoring 1 (17.2%) and scoring 0 (1.7%).
      Multivariate analysis selected age and the Sabadell score as the only variables
      associated with ward mortality, with an area under the receiver operating curve
      of 0.88 (95% CI 0.84-0.93) for the Sabadell score. CONCLUSION: The Sabadell score
      at ICU discharge works effectively to stratify patients according to hospital
      outcome.

PMID- 17192175
TI  - A proteomics study of the response of North Ronaldsay sheep to copper challenge.
AB  - BACKGROUND: The objective of this proteomics study was to identify proteins that
      changed expression as a result of copper challenge in the uniquely copper
      sensitive North Ronaldsay sheep and further, to compare those changes in
      expression with the more copper tolerant Cambridge breed. Such data gives us a
      proteome-centered perspective of the pathogenesis of copper-induced oxidative
      stress in this breed. RESULTS: Many proteins respond to copper challenge, but
      this study focuses on those exhibiting a differential response between the two
      breeds, related to liver copper content. As copper accumulated in the tissue, the
      pattern of expression of several proteins was markedly different, in North
      Ronaldsay sheep as compared to the Cambridge breed. CONCLUSION: The pattern of
      changes was consistent with the greatly enhanced susceptibility of North
      Ronaldsay sheep to copper-induced oxidative stress, focused on mitochondrial
      disturbance with consequent activation of hepatic stellate cells. The expression
      profiles were sufficiently complex that the response could not simply be
      explained as a hypersensitivity to copper in North Ronaldsay sheep.

PMID- 17192176
TI  - Pain during ice water test distinguishes clinical bladder hypersensitivity from
      overactivity disorders.
AB  - BACKGROUND: The Bladder cooling reflex (BCR) i.e. uninhibited detrusor
      contractions evoked by intravesical instillation of cold saline, is a segmental
      reflex believed to be triggered by menthol sensitive cold receptors in the
      bladder wall, with the afferent signals transmitted by C fibres. The BCR is a
      neonatal reflex that becomes suppressed by descending signals from higher centres
      at approximately the time when the child gains full voluntary control of voiding.
      It re-emerges in adults with neurogenic detrusor overactivity as a consequence of
      loss of central descending inhibition, resulting from conditions such as spinal
      cord injury or multiple sclerosis. We have recently shown an increase of nerve
      fibres expressing the cool and menthol receptor TRPM8 in both overactive (IDO)
      and painful bladder syndrome (PBS), but its functional significance is unknown.
      We have therefore studied the bladder cooling reflex and associated sensory
      symptoms in patients with PBS and overactivity disorders. METHODS: The BCR,
      elicited by ice water test (IWT) was performed in patients with painful bladder
      syndrome (PBS, n = 17), idiopathic detrusor overactivity (IDO, n = 22),
      neurogenic detrusor overactivity (NDO, n = 4) and stress urinary incontinence (as
      controls, n = 21). The IWT was performed by intravesical instillation of cold
      saline (0 - 4 degrees C). A positive IWT was defined as presence of uninhibited
      detrusor contraction evoked by cold saline, associated with urgency or with fluid
      expulsion. Patients were asked to report and rate any pain and cold sensation
      during the test. RESULTS: A positive IWT was observed in IDO (6/22, 27.3%) and
      NDO (4/4, 100%) patients, but was negative in all control and PBS patients.
      Thirteen (76.5%) PBS patients reported pain during the IWT, with significantly
      higher pain scores during ice water instillation compared to the baseline (P =
      0.0002), or equivalent amount of bladder filling (100 mls) with saline at room
      temperature (P = 0.015). None of the control or overactive (NDO/IDO) patients
      reported any pain during the IWT. CONCLUSION: The BCR in DO may reflect loss of
      central inhibition, which appears necessary to elicit this reflex; the pain
      elicited in PBS suggests afferent sensitisation, hence sensory symptoms are
      evoked but not reflex detrusor contractions. The ice water test may be a useful
      and simple marker for clinical trials in PBS, particularly for novel selective
      TRPM8 antagonists.

PMID- 17192178
TI  - Consequences of infertility in developing countries: results of a questionnaire
      and interview survey in the South of Vietnam.
AB  - BACKGROUND: This study explores the psychological, socio-cultural and economic
      consequences of infertility on couples' life. The purpose of this research is to
      improve knowledge about the potentially serious implications of infertility in
      the South of Vietnam. METHODS: This study included 118 infertile couples who
      filled in questionnaires and 28 men and women who were interviewed. RESULTS: Data
      of the questionnaire show men and women do not differ in their responses and
      attitudes towards infertility. Almost one-third of the participants require
      psychological support. Interviewees experience secrecy, social pressure and
      economic hardship. CONCLUSION: Offspring are very important to Vietnamese
      couples. Their future depends on children. Family plays an important role in the
      experiences of the infertile couple. Economic consequences are a particular
      distressing factor. There is a need for psychological counselling in the
      treatment of infertile couples in the South of Vietnam. It should be realised
      that in developing countries, despite overpopulation, unwanted childlessness is
      an important social and economical burden that needs attention.

PMID- 17192177
TI  - Lutein is needed for efficient chlorophyll triplet quenching in the major LHCII
      antenna complex of higher plants and effective photoprotection in vivo under
      strong light.
AB  - BACKGROUND: Lutein is the most abundant xanthophyll in the photosynthetic
      apparatus of higher plants. It binds to site L1 of all Lhc proteins, whose
      occupancy is indispensable for protein folding and quenching chlorophyll
      triplets. Thus, the lack of a visible phenotype in mutants lacking lutein has
      been surprising. RESULTS: We have re-assessed the lut2.1 phenotypes through
      biochemical and spectroscopic methods. Lhc proteins from the lut2.1 mutant
      compensate the lack of lutein by binding violaxanthin in sites L1 and L2. This
      substitution reduces the capacity for regulatory mechanisms such as NPQ, reduces
      antenna size, induces the compensatory synthesis of Antheraxanthin + Zeaxanthin,
      and prevents the trimerization of LHCII complexes. In vitro reconstitution shows
      that the lack of lutein per se is sufficient to prevent trimerization. lut2.1
      showed a reduced capacity for state I-state II transitions, a selective
      degradation of Lhcb1 and 2, and a higher level of photodamage in high light
      and/or low temperature, suggesting that violaxanthin cannot fully restore
      chlorophyll triplet quenching. In vitro photobleaching experiments and time
      resolved spectroscopy of carotenoid triplet formation confirmed this hypothesis.
      The npq1lut2.1 double mutant, lacking both zeaxanthin and lutein, is highly
      susceptible to light stress. CONCLUSION: Lutein has the specific property of
      quenching harmful 3Chl* by binding at site L1 of the major LHCII complex and of
      other Lhc proteins of plants, thus preventing ROS formation. Substitution of
      lutein by violaxanthin decreases the efficiency of 3Chl* quenching and causes
      higher ROS yield. The phenotype of lut2.1 mutant in low light is weak only
      because rescuing mechanisms of photoprotection, namely zeaxanthin synthesis,
      compensate for the ROS production. We conclude that zeaxanthin is effective in
      photoprotection of plants lacking lutein due to the multiple effects of
      zeaxanthin in photoprotection, including ROS scavenging and direct quenching of
      Chl fluorescence by binding to the L2 allosteric site of Lhc proteins.

PMID- 17192180
TI  - 'Libyan Trial': a verdict running counter to scientific evidence.
AB  - Sidaction's appeal regarding the sentencing of medical personnels in the Libyan
      HIV infection cases.

PMID- 17192179
TI  - Nectin-2-mediated entry of a syncytial strain of herpes simplex virus via pH
      independent fusion with the plasma membrane of Chinese hamster ovary cells.
AB  - BACKGROUND: Herpes simplex virus (HSV) can utilize multiple pathways to enter
      host cells. The factors that determine which route is taken are not clear.
      Chinese hamster ovary (CHO) cells that express glycoprotein D (gD)-binding
      receptors are model cells that support a pH-dependent, endocytic entry pathway
      for all HSV strains tested to date. Fusion-from-without (FFWO) is the induction
      of target cell fusion by addition of intact virions to cell monolayers in the
      absence of viral protein expression. The receptor requirements for HSV-induced
      FFWO are not known. We used the syncytial HSV-1 strain ANG path as a tool to
      evaluate the complex interplay between receptor usage, membrane fusion, and
      selection of entry pathway. RESULTS: Inhibitors of endocytosis and endosome
      acidification blocked ANG path entry into CHO cells expressing nectin-1
      receptors, but not CHO-nectin-2 cells. Thus, under these conditions, nectin-2
      mediates pH-independent entry at the plasma membrane. In addition, CHO-nectin-2
      cells supported pH-dependent, endocytic entry of different strains of HSV-1,
      including rid1 and HFEM. The kinetics of ANG path entry was rapid (t1/2 of 5-10
      min) regardless of entry route. However, HSV-1 ANG path entry by fusion with the
      CHO-nectin-2 cell plasma membrane was more efficient and resulted in larger
      syncytia. ANG path virions added to the surface of CHO-nectin-2 cells, but not
      receptor-negative CHO cells or CHO-nectin-1 cells, induced rapid FFWO.
      CONCLUSION: HSV-1 ANG path can enter CHO cells by either endocytic or non
      endocytic pathways depending on whether nectin-1 or nectin-2 is present. In
      addition to these cellular receptors, one or more viral determinants is important
      for the selection of entry pathway. HSV-induced FFWO depends on the presence of
      an appropriate gD-receptor in the target membrane. Nectin-1 and nectin-2 target
      ANG path to divergent cellular pathways, and these receptors may have different
      roles in triggering viral membrane fusion.

PMID- 17192181
TI  - A huge omental lymphangioma with extension into labia majorae: a case report.
AB  - BACKGROUND: Abdominal cystic lymphangiomas are uncommon congenital benign tumors.
      CASE PRESENTATION: We present a case of a 4 year old female child with a cystic
      lymphangioma arising from greater omentum and occupying whole of the abdomen and
      protruding through labia mejora. Ultrasonography and CT scan confirmed the
      diagnosis. Complete excision of the cyst along with omentectomy done with no
      clinical or radiological evidence of recurrence till 6 months. CONCLUSION: Due to
      variable presentation of abdominal lymphangiomas, extensive imaging studies are
      necessary for evaluation and diagnosis. Complete surgical resection is a
      treatment of choice.

PMID- 17192182
TI  - Therapeutic approach to "downhill" esophageal varices bleeding due to superior
      vena cava syndrome in Behcet's disease: a case report.
AB  - BACKGROUND: One of the rare presentations of superior vena cava syndrome is
      bleeding of "downhill" esophageal varices (DEV) and different approaches have
      been used to control it. This is a case report whose DEV was eradicated by band
      ligation for the first time. CASE PRESENTATION: We report a 42-year-old man who
      is a known case of Behcet's disease. The patient's first presentation was
      superior vena cava syndrome due to thrombosis followed by bipolar ulcers and
      arthralgia. He received warfarin, prednisolone and azathioprine. The clinical
      course of the patient was complicated by one episode of hematemesis without
      abdominal pain when the patient's PT was in therapeutic range. After
      resuscitation and correction of PT with fresh frozen plasma transfusion, upper
      gastrointestinal endoscopy was done. Prominent varices were seen in the upper
      third of the esophagus, tapering to the middle part without acute bleeding.
      Stomach and duodenum were normal. Color ultrasonography evaluation of the portal,
      hepatic and splenic veins was negative for thrombosis. Band ligation was done and
      the patient's bleeding did not recur. CONCLUSION: Band ligation is a safe and
      effective method for controlling DEV bleeding in patients with uncorrectable
      underlying disorders.

PMID- 17192183
TI  - Surgical correction of unsuccessful derotational humeral osteotomy in obstetric
      brachial plexus palsy: evidence of the significance of scapular deformity in the
      pathophysiology of the medial rotation contracture.
AB  - BACKGROUND: The current method of treatment for persistent internal rotation due
      to the medial rotation contracture in patients with obstetric brachial plexus
      injury is humeral derotational osteotomy. While this procedure places the arm in
      a more functional position, it does not attend to the abnormal glenohumeral
      joint. Poor positioning of the humeral head secondary to elevation and rotation
      of the scapula and elongated acromion impingement causes functional limitations
      which are not addressed by derotation of the humerus. Progressive dislocation,
      caused by the abnormal positioning and shape of the scapula and clavicle, needs
      to be treated more directly. METHODS: Four patients with Scapular Hypoplasia,
      Elevation And Rotation (SHEAR) deformity who had undergone unsuccessful humeral
      osteotomies to treat internal rotation underwent acromion and clavicular
      osteotomy, ostectomy of the superomedial border of the scapula and posterior
      capsulorrhaphy in order to relieve the torsion developed in the acromio
      clavicular triangle by persistent asymmetric muscle action and medial rotation
      contracture. RESULTS: Clinical examination shows significant improvement in the
      functional movement possible for these four children as assessed by the modified
      Mallet scoring, definitely improving on what was achieved by humeral osteotomy.
      CONCLUSION: These results reveal the importance of recognizing the presence of
      scapular hypoplasia, elevation and rotation deformity before deciding on a
      treatment plan. The Triangle Tilt procedure aims to relieve the forces acting on
      the shoulder joint and improve the situation of the humeral head in the glenoid.
      Improvement in glenohumeral positioning should allow for better functional
      movements of the shoulder, which was seen in all four patients. These dramatic
      improvements were only possible once the glenohumeral deformity was directly
      addressed surgically.

PMID- 17192184
TI  - Traditional management of ear, nose and throat (ENT) diseases in Central Kenya.
AB  - Diseases of ear, nose and throat (ENT) often have serious consequences including
      hearing impairment, and emotional strain that lower the quality of life of
      patients. In Kenya, upper respiratory infections are among the most common
      infections encountered in outpatient facilities. Some of these infections are
      becoming difficult to control because some of the causing microorganisms have
      acquired antibiotic resistance and hence the need to develop new drugs with
      higher efficacy. Ethnobotanical studies have now been found to be instrumental in
      improving chances of discovering plants with antimicrobial activity in new drug
      development. In Kenya the majority of local people are turning to herbal remedies
      for primary health care needs. In most cases the sources of these remedies are
      undocumented and the knowledge about them passed orally form generation to
      generation, hence under threat of disappearing with current rates of
      modernisation. This study explored the traditional remedies used in managing
      various ENT diseases in seven districts of the Central Province of Kenya. The
      most common ENT conditions managed using traditional therapies include: common
      cold, cough, tonsillitis, otitis-media, chest pains and asthma. The results
      indicate that 67 species belonging to 36 plant families were utilized in this
      region. These plants were of varying habits; herbs (37.3%), shrubs (34.4%), trees
      (25.4%) as well as some grasses and sedges (3%). The traditional preparations
      were found to be made mainly from leaves (49%), roots (20.5%) and barks (12.5%).
      For each of the ENT conditions multiple species are utilized mainly as individual
      preparations but occasionally as polyherbal concoctions. In the case of common
      cold for example, 30 different species are used. Plants reported in this survey
      are important candidates for antimicrobial tests against ENT disease causing
      micro-organisms, especially those with antibiotic resistance.

PMID- 17192185
TI  - Up-regulation of HLA class-I antigen expression and antigen-specific CTL response
      in cervical cancer cells by the demethylating agent hydralazine and the histone
      deacetylase inhibitor valproic acid.
AB  - BACKGROUND: DNA hypermethylation and histone deacetylation are epigenetic events
      that contribute to the absence or downregulated expression of different
      components of the tumor recognition complex. These events affect the processing
      and presentation of antigenic peptides to CTLs by HLA class-I molecules. In this
      work evaluated the effect of the DNA hypomethylating agent hydralazine and the
      histone deacetylase inhibitor valproic acid, on the expression of HLA class-I
      molecules and on the antigen-specific immune recognition of cervical cancer
      cells. METHODS: Cell lines C33A (HPV-), CaSki (HPV-16+) and MS751 (HPV-18+) were
      treated with hydralazine and valproic acid to assess the expression of HLA class
      I molecules by flow cytometry and RT-PCR. Promoter methylation of HLA class-I -A,
      -B and C, was also evaluated by Methylation-Specific PCR. Primary cervical tumors
      of four HLA-A*0201 allele patients were typed for HPV and their CTL's stimulated
      in vitro with the T2 cell line previously loaded with 50 microM of the HPV
      peptides. Cytotoxicity of stimulated CTL's was assayed against Caski and MS751
      cells pre-treated with hydralazine and valproic acid. RESULTS: Valproic acid and
      hydralazine/valproic acid up-regulated the constitutive HLA class-I expression as
      evaluated by flow cytometry and RT-PCR despite constitutive promoter
      demethylation at these loci. Hydralazine and valproic acid in combination but no
      IFN-gamma hyperacetylated histone H4 as evaluated by ChiP assay. The antigenic
      immune recognition of CaSki and MS751 cells by CTLs specific to HPV-16/18 E6 and
      E7-derived epitopes, was increased by VA and H/VA and the combination of H/VA/IFN
      gamma. CONCLUSION: These results support the potential use of hydralazine and
      valproic acid as an adjuvant for immune intervention in cervical cancer patients
      whenever clinical protocols based on tumor antigen recognition is desirable, like
      in those cases where the application of E6 and E7 based therapeutic vaccines is
      used.

PMID- 17192187
TI  - Human papillomavirus typing of invasive cervical cancers in Italy.
AB  - BACKGROUND: Human papilloma viruses (HPV) are the necessary cause of invasive
      cervical cancer (ICC). Of the many different types identified so far, only a few
      of them account for the great majority of cases worldwide, with geographical
      differences in their distribution. Data on the local distribution are now of
      interest in view of the soon-to-come introduction of HPV type-specific
      prophylactic vaccines. RESULTS: We have investigated HPV type distribution in
      samples of 48 ICC cases occurred in women living in North-East Italy in the years
      1997-1999. Cases were extracted from the Venetian Tumour Registry files, as
      incident cases whose specimens had been processed in two Pathology Departments.
      Search and typing were performed by polymerase chain reaction (PCR) using
      GP5+/GP6+ primers, followed by direct sequencing or reverse dot blot. Three cases
      were PCR negative using the housekeeping primers and hence excluded. One case was
      negative by all HPV tests used. HPV 16 was present in 32 (72.7%) cases, as single
      infection in 28, in mixed infection in 4. Of the 44 positive cases, HPV 16 and
      HPV 18 accounted for 33 (75%), as single or mixed infections. The other high risk
      HPV types accounted for 11 (25%) of the remaining infections. Of the 32 HPV 16
      positive cases, sequencing of the E6 gene could be performed in 25; the prototype
      isolate was identified in 7, and the variant T350G in 18; in 4 cases one or more
      additional mutations were present. CONCLUSIONS: Our results suggest that HPV 16
      has a very high prevalence among women with invasive cervical cancer in Italy;
      therefore, the use of a prophylactic vaccine for HPV types 16 and 18 could
      prevent up to 75% of invasive cervical cancers in Italy.

PMID- 17192188
TI  - Chronic productive cough in school children: prevalence and associations with
      asthma and environmental tobacco smoke exposure.
AB  - BACKGROUND: The relationships between chronic productive cough (CPC),
      environmental tobacco smoke (ETS) exposure, and asthma are not clearly
      established in children. Therefore, we wished to determine the prevalence of CPC
      and examine the relationships between CPC, ETS exposure, and asthma in young
      teenagers. METHODS: We performed a cross sectional survey of 2397 Seattle middle
      school students, 11-15 years old, using written and video respiratory-symptom
      questionnaires. We defined CPC as--daily cough productive of phlegm for at least
      3 months out of the year; current asthma as--yes to "Have you had wheezing or
      whistling in your chest in the past 12 months?" and yes in the past year to any
      of the four video wheezing/asthma video scenarios; and ETS exposure as exposed to
      tobacco smoke at least several hours each day. We used multilogistic regression
      to examine relationships between CPC, asthma, and ETS exposure and included in
      the model the potentially confounding variables race, gender, and allergic
      rhinitis. RESULTS: The prevalence of CPC was 7.2%. Forty-seven percent (82/173)
      of children with CPC met criteria for current asthma, while only 10% (214/2224)
      of those without CPC had current asthma. Current asthma had the strongest
      associated with CPC, odds ratio (OR) 6.4 [95% CI 4.5-9.0], and ETS was
      independently associated with both CPC, OR 2.7 [1.8-4.1] and asthma, OR 2.7 [1.5
      4.7]. CONCLUSION: In a population of young teenagers, CPC was strongly associated
      with report of current asthma symptoms and also with ETS exposure. This suggests
      that asthma and ETS exposure may contribute to CPC in children. However, this
      study was not designed to determine whether asthma was the actual cause of CPC in
      this population of children.

PMID- 17192186
TI  - ICI 182,780 has agonistic effects and synergizes with estradiol-17 beta in fish
      liver, but not in testis.
AB  - BACKGROUND: ICI 182,780 (ICI) belongs to a new class of antiestrogens developed
      to be pure estrogen antagonists and, in addition to its therapeutic use, it has
      been used to knock-out estrogen and estrogen receptor (ER) actions in several
      mammalian species. In the present study, the effects and mechanism of action of
      ICI were investigated in the teleost fish, sea bream (Sparus auratus). METHODS:
      Three independent in vivo experiments were performed in which mature male tilapia
      (Oreochromis mossambicus) or sea bream received intra-peritoneal implants
      containing estradiol-17 beta (E2), ICI or a combination of both compounds. The
      effects of E2 and ICI on plasma calcium levels were measured and hepatic and
      testicular gene expression of the three ER subtypes, ER alpha, ER beta a and ER
      beta b, and the estrogen-responsive genes, vitellogenin II and choriogenin L,
      were analyzed by semi-quantitative RT-PCR in sea bream. RESULTS: E2 treatment
      caused an increase in calcium levels in tilapia, while ICI alone had no
      noticeable effect, as expected. However, pretreatment with ICI synergistically
      potentiated the effect of E2 on plasma calcium in both species. ICI mimicked some
      E2 actions in gene expression in sea bream liver upregulating ER alpha,
      vitellogenin II and choriogenin L, although, unlike E2, it did not downregulate
      ER beta a and ER beta b. In contrast, no effects of E2 or ICI alone were detected
      in the expression of ERs in testis, while vitellogenin II and choriogenin L were
      upregulated by E2 but not ICI. Finally, pretreatment with ICI had a synergistic
      effect on the hepatic E2 down-regulation of ER beta b, but apparently blocked the
      ER alpha up-regulation by E2. CONCLUSION: These results demonstrate that ICI has
      agonistic effects on several typical estrogenic responses in fish, but its
      actions are tissue-specific. The mechanisms for the ICI agonistic activity are
      still unknown; although the ICI induced up-regulation of ER alpha mRNA could be
      one of the factors contributing to the cellular response.

PMID- 17192189
TI  - SIGMA: a system for integrative genomic microarray analysis of cancer genomes.
AB  - BACKGROUND: The prevalence of high resolution profiling of genomes has created a
      need for the integrative analysis of information generated from multiple
      methodologies and platforms. Although the majority of data in the public domain
      are gene expression profiles, and expression analysis software are available, the
      increase of array CGH studies has enabled integration of high throughput genomic
      and gene expression datasets. However, tools for direct mining and analysis of
      array CGH data are limited. Hence, there is a great need for analytical and
      display software tailored to cross platform integrative analysis of cancer
      genomes. RESULTS: We have created a user-friendly java application to facilitate
      sophisticated visualization and analysis such as cross-tumor and cross-platform
      comparisons. To demonstrate the utility of this software, we assembled array CGH
      data representing Affymetrix SNP chip, Stanford cDNA arrays and whole genome
      tiling path array platforms for cross comparison. This cancer genome database
      contains 267 profiles from commonly used cancer cell lines representing 14
      different tissue types. CONCLUSION: In this study we have developed an
      application for the visualization and analysis of data from high resolution array
      CGH platforms that can be adapted for analysis of multiple types of high
      throughput genomic datasets. Furthermore, we invite researchers using array CGH
      technology to deposit both their raw and processed data, as this will be a
      continually expanding database of cancer genomes. This publicly available
      resource, the System for Integrative Genomic Microarray Analysis (SIGMA) of
      cancer genomes, can be accessed at http://sigma.bccrc.ca.

PMID- 17192191
TI  - Intracerebral administration of interleukin-12 (IL-12) and IL-18 modifies the
      course of mouse scrapie.
AB  - BACKGROUND: Prion diseases are characterised by a neurodegenerative pattern in
      which the function of immune system remains still elusive. In the present study,
      we evaluate if an exogenous treatment with Interleukin-12 (IL-12) and IL-18, able
      to activate microglia, is able to affect scrapie pathogenesis. RESULTS: Cytokines
      injected intracranially, induced a strong inflammatory response characterised by
      TNF-alpha production and microglia activation. Two groups of mice were injected
      intracerebrally with high dose of ME7 strain of scrapie containing IL-12 and IL
      18 or sterile saline. Cytokines-treated mice showed a more pronounced
      accumulation of PrPSc in brain tissues at 90 days post-inoculation and a shorter
      mean survival times than untreated mice. CONCLUSION: We can conclude that
      intracerebral administration of IL-12 and IL-18 can modulate scrapie pathogenesis
      possibly through a microglia-mediated pattern.

PMID- 17192190
TI  - Reduced repair of 8-hydroxyguanine in the human breast cancer cell line, HCC1937.
AB  - BACKGROUND: Breast cancer is the second leading cause of cancer deaths in women
      in the United States. Although the causes of this disease are incompletely
      understood, oxidative DNA damage is presumed to play a critical role in breast
      carcinogenesis. A common oxidatively induced DNA lesion is 8-hydroxyguanine (8-OH
      Gua), which has been implicated in carcinogenesis. The aim of this study was to
      investigate the ability of HCC1937 and MCF-7 breast cancer cell lines to repair 8
      OH-Gua relative to a nonmalignant human mammary epithelial cell line, AG11134.
      METHODS: We used oligonucleotide incision assay to analyze the ability of the two
      breast cancer cell lines to incise 8-OH-Gua relative to the control cell line.
      Liquid chromatography/mass spectrometry (LC/MS) was used to measure the levels of
      8-OH-Gua as its nucleoside, 8-OH-dG in the cell lines after exposure to H2O2
      followed by 30 min repair period. Protein expression levels were determined by
      Western blot analysis, while the hOGG1 mRNA levels were analyzed by RT-PCR.
      Complementation of hOGG1 activity in HCC1937 cells was assessed by addition of
      the purified protein in the incision assay, and in vivo by transfection of
      pFlagCMV-4-hOGG1. Clonogenic survival assay was used to determine sensitivity
      after H2O2-mediated oxidative stress. RESULTS: We show that the HCC1937 breast
      cancer cells have diminished ability to incise 8-OH-Gua and they accumulate
      higher levels of 8-OH-dG in the nuclear genome after H2O2 treatment despite a 30
      min repair period when compared to the nonmalignant mammary cells. The defective
      incision of 8-OH-Gua was consistent with expression of undetectable amounts of
      hOGG1 in HCC1937 cells. The reduced incision activity was significantly
      stimulated by addition of purified hOGG1. Furthermore, transfection of pFlagCMV-4
      hOGG1 in HCC1937 cells resulted in enhanced incision of 8-OH-Gua. HCC1937 cells
      are more sensitive to high levels of H2O2 and have up-regulated SOD1 and SOD2.
      CONCLUSION: This study provides evidence for inefficient repair of 8-OH-Gua in
      HCC1937 breast cancer cell line and directly implicates hOGG1 in this defect.

PMID- 17192192
TI  - Soy foods have low glycemic and insulin response indices in normal weight
      subjects.
AB  - BACKGROUND: Foods with a low glycemic index (GI) may provide a variety of health
      benefits. The objective of the present study was to measure the GI and insulin
      index (II) of select soy foods. METHODS: The study was conducted in two parts
      with low-carbohydrate products being tested separately. In Experiment 1, subjects
      averaged 23.2 years of age with BMI = 22.0 kg/m2, while subjects in Experiment 2
      averaged 23.9 years of age with BMI = 21.6 kg/m2. The reference (glucose) and
      test foods were served in portions containing 10 g of carbohydrates in Experiment
      1 (two test foods) and 25 g of carbohydrates in Experiment 2 (four test foods).
      Subjects consumed the reference food twice and each test food once. For each
      test, subjects were instructed to consume a fixed portion of the reference food
      or test food together with 250 g of water within 12 min. Blood samples were
      collected before each test and at 15, 30, 45, 60, 90, and 120 min after
      consumption of reference or test foods to quantify glucose and insulin. Two-hour
      blood glucose and plasma insulin curves were constructed and areas under the
      curves were calculated. GI and II values for each subject and test food were
      calculated. RESULTS: In Experiment 1, both low-carbohydrate soy foods were shown
      to have significantly (P < 0.05) lower GI and II values than the reference food.
      In Experiment 2, three of the four test foods had significantly (P < 0.05) lower
      GI and II values than the reference food. CONCLUSION: All but one of the soy
      foods tested had a low GI, suggesting that soy foods may be an appropriate part
      of diets intended to improve control of blood glucose and insulin levels.

PMID- 17192193
TI  - Acyl-CoA-binding and self-associating properties of a recombinant 13.3 kDa N
      terminal fragment of diacylglycerol acyltransferase-1 from oilseed rape.
AB  - BACKGROUND: Diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the acyl
      CoA-dependent acylation of sn-1, 2-diacylglycerol to generate triacylglycerol and
      CoA. The deduced amino acid sequence of cDNAs encoding DGAT1 from plants and
      mammals exhibit a hydrophilic N-terminal region followed by a number of potential
      membrane-spanning segments, which is consistent with the membrane-bound nature of
      this enzyme family. In order to gain insight into the structure/function
      properties of DGAT1 from Brassica napus (BnDGAT1), we produced and partially
      characterized a recombinant polyHis-tagged N-terminal fragment of the enzyme,
      BnDGAT1(1-116)His6, with calculated molecular mass of 13,278 Da. RESULTS:
      BnDGAT1(1-116)His6 was highly purified from bacterial lysate and plate-like
      monoclinic crystals were grown using this preparation. Lipidex-1000 binding
      assays and gel electrophoresis indicated that BnDGAT1(1-116)His6 interacts with
      long chain acyl-CoA. The enzyme fragment displayed enhanced affinity for erucoyl
      (22:1cisDelta13)-CoA over oleoyl (18:1cisDelta9)-CoA, and the binding process
      displayed positive cooperativity. Gel filtration chromatography and cross-linking
      studies indicated that BnDGAT1(1-116)His6 self-associated to form a tetramer.
      Polyclonal antibodies raised against a peptide of 15 amino acid residues
      representing a segment of BnDGAT1(1-116)His6 failed to react with protein in
      microsomal vesicles following treatment with proteinase K, suggesting that the N
      terminal fragment of BnDGAT1 was localized to the cytosolic side of the ER.
      CONCLUSION: Collectively, these results suggest that BnDGAT1 may be
      allosterically modulated by acyl-CoA through the N-terminal region and that the
      enzyme self-associates via interactions on the cytosolic side of the ER.

PMID- 17192194
TI  - Compressive loading at the end plate directly regulates flow and deformation of
      the basivertebral vein: an analytical study.
AB  - BACKGROUND: Metastatic diseases and infections frequently involve the spine. This
      is the result of seeding of the vertebral body by tumor cells or bacteria
      delivered by venous blood from Batson's plexus, which is hypothesized to enter
      the vertebral body via the epidural veins. Isolated spinal segments deform
      significantly at the bony end plate when under compression. This deformation
      could cause a volume change of the vertebral body and may be accompanied by
      retrograde flow of venous blood. To date, this process has not been investigated
      quantitatively. The purpose of this study was to determine the volume changes of
      the vertebral body and basivertebral vein for a vertebral body under compression.
      METHODS: A three-dimensional finite element mesh model of the L4 segment with
      both adjacent discs was modified from a 3-D computed tomography scan image. An
      octagon representing the basivertebral vein was introduced into the center of the
      vertebral body in the model. Four compressive orientations (1500 N) were applied
      on the top disc. The volume change of the vertebral body model and the
      basivertebral vein were then computed. RESULTS: The volume change of the
      vertebral body was about 0.1 cm3 (16.3% of the basivertebral vein) for the four
      loading conditions. The maximum cross-sectional area reductions of the
      basivertebral vein and volume reduction were 1.54% and 1.02%, for uniform
      compression. CONCLUSION: Our study quantified the small but significant volume
      change of a modeled vertebral body and cross-sectional areas and that of the
      basivertebral vein, due to the inward bulging of the end plate under compression.
      This volume change could initiate the reverse flow of blood from the epidural
      venous system and cause seeding of tumors or bacterial cells.

PMID- 17192195
TI  - Generation and characterization of a stable cell population releasing fluorescent
      HIV-1-based Virus Like Particles in an inducible way.
AB  - BACKGROUND: The availability of cell lines releasing fluorescent viral particles
      can significantly support a variety of investigations, including the study of
      virus-cell interaction and the screening of antiviral compounds. Regarding HIV-1,
      the recovery of such biologic reagents represents a very hard challenge due to
      the intrinsic cytotoxicity of many HIV-1 products. We sought to overcome such a
      limitation by using a cell line releasing HIV-1 particles in an inducible way,
      and by exploiting the ability of a HIV-1 Nef mutant to be incorporated in virions
      at quite high levels. RESULTS: Here, we report the isolation and characterization
      of a HIV-1 packaging cell line, termed 18-4s, able to release valuable amounts of
      fluorescent HIV-1 based Virus-Like Particles (VLPs) in an inducible way. 18-4s
      cells were recovered by constitutively expressing the HIV-1 NefG3C mutant fused
      with the enhanced-green fluorescent protein (NefG3C-GFP) in a previously isolated
      inducible HIV-1 packaging cell line. The G3C mutation creates a palmitoylation
      site which results in NefG3C-GFP incorporation into virions greatly exceeding
      that of the wild type counterpart. Upon induction of 18-4s cells with ponasterone
      A and sodium butyrate, up to 4 mug/ml of VLPs, which had incorporated about 150
      molecules of NefG3C-GFP per viral particle, were released into the culture
      supernatant. Due to their intrinsic strong fluorescence, the 18-4s VLPs were
      easily detectable by a novel cytofluorometric-based assay developed here. The
      treatment of target cells with fluorescent 18-4 VLPs pseudotyped with different
      glycoprotein receptors resulted in these becoming fluorescent as early as two
      hours post-challenge. CONCLUSION: We created a stable cell line releasing
      fluorescent HIV-1 based VLPs upon induction useful for several applications
      including the study of virus-cell interactions and the screening of antiviral
      compounds.

PMID- 17192197
TI  - The effect of the holiday season on body weight and composition in college
      students.
AB  - BACKGROUND: With the rapid increase in obesity rates, determining critical
      periods for weight gain and the effects of changes in fat mass is imperative. The
      purpose of this study was to examine changes in body weight and composition over
      the holiday season (Thanksgiving through New Year's) in male and female college
      students. METHODS: Subjects completed three visits: the first occurred within 2
      weeks prior to Thanksgiving, the second occurred within 5 to 7 days following
      Thanksgiving, and the third occurred within 10 days following New Year's Day. A
      total of 82 healthy male and female college age subjects participated. Body
      composition by dual energy x-ray absorptiometry (DXA) was assessed at visits 1
      and 3 while body weight was assessed at all three visits. RESULTS: Average body
      weight remained relatively unchanged from pre-Thanksgiving to post-New Year's
      (71.3 +/- 14 kg vs. 71.2 +/- 15 kg; P = 0.71) and, in fact, a subset of normal
      weight subjects lost a significant amount of body weight. However, percent body
      fat (25.9 +/- 9 %fat vs. 27.0 +/- 9 %fat; P < 0.01) and fat mass (18.3 +/- 8 kg
      and 19.1 +/- 8 kg; P < 0.01) significantly increased from pre-Thanksgiving to
      post-New Year's while fat-free mass (48.7 +/- 12 kg and 48.3 +/- 11 kg; P = 0.08)
      was not significantly different than the post-New Year's. A significant positive
      relationship (P < 0.001) between the change in BMI and percent fat, total fat
      mass, total fat free mass, and trunk fat mass for the pre-Thanksgiving and post
      New Year's visits were found. The same significant positive relationships (P <
      0.001) were also observed between the change in body weight and percent fat,
      total fat mass, total fat free mass, and trunk fat mass. CONCLUSION: Despite the
      fact that body weight remained unchanged over the course of the holiday season, a
      significant increase in %body fat and fat mass was observed. With recent evidence
      showing marked morbidity and mortality to be associated with increased body fat
      (particularly abdominal adiposity), results from this study suggest body weight
      alone may underestimate the potentially deleterious effects of the holiday
      season.

PMID- 17192196
TI  - Alternative splicing and differential gene expression in colon cancer detected by
      a whole genome exon array.
AB  - BACKGROUND: Alternative splicing is a mechanism for increasing protein diversity
      by excluding or including exons during post-transcriptional processing.
      Alternatively spliced proteins are particularly relevant in oncology since they
      may contribute to the etiology of cancer, provide selective drug targets, or
      serve as a marker set for cancer diagnosis. While conventional identification of
      splice variants generally targets individual genes, we present here a new exon
      centric array (GeneChip Human Exon 1.0 ST) that allows genome-wide identification
      of differential splice variation, and concurrently provides a flexible and
      inclusive analysis of gene expression. RESULTS: We analyzed 20 paired tumor
      normal colon cancer samples using a microarray designed to detect over one
      million putative exons that can be virtually assembled into potential gene-level
      transcripts according to various levels of prior supporting evidence. Analysis of
      high confidence (empirically supported) transcripts identified 160 differentially
      expressed genes, with 42 genes occupying a network impacting cell proliferation
      and another twenty nine genes with unknown functions. A more speculative
      analysis, including transcripts based solely on computational prediction,
      produced another 160 differentially expressed genes, three-fourths of which have
      no previous annotation. We also present a comparison of gene signal estimations
      from the Exon 1.0 ST and the U133 Plus 2.0 arrays. Novel splicing events were
      predicted by experimental algorithms that compare the relative contribution of
      each exon to the cognate transcript intensity in each tissue. The resulting
      candidate splice variants were validated with RT-PCR. We found nine genes that
      were differentially spliced between colon tumors and normal colon tissues,
      several of which have not been previously implicated in cancer. Top scoring
      candidates from our analysis were also found to substantially overlap with EST
      based bioinformatic predictions of alternative splicing in cancer. CONCLUSION:
      Differential expression of high confidence transcripts correlated extremely well
      with known cancer genes and pathways, suggesting that the more speculative
      transcripts, largely based solely on computational prediction and mostly with no
      previous annotation, might be novel targets in colon cancer. Five of the
      identified splicing events affect mediators of cytoskeletal organization (ACTN1,
      VCL, CALD1, CTTN, TPM1), two affect extracellular matrix proteins (FN1, COL6A3)
      and another participates in integrin signaling (SLC3A2). Altogether they form a
      pattern of colon-cancer specific alterations that may particularly impact cell
      motility.

PMID- 17192198
TI  - Influenza pandemic and professional duty: family or patients first? A survey of
      hospital employees.
AB  - BACKGROUND: Conflicts between professional duties and fear of influenza
      transmission to family members may arise among health care professionals (HCP).
      METHODS: We surveyed employees at our university hospital regarding ethical
      issues arising during the management of an influenza pandemic. RESULTS: Of 644
      respondents, 182 (28%) agreed that it would be professionally acceptable for HCP
      to abandon their workplace during a pandemic in order to protect themselves and
      their families, 337 (52%) disagreed with this statement and 125 (19%) had no
      opinion, with a higher rate of disagreement among physicians (65%) and nurses
      (54%) compared with administrators (32%). Of all respondents, 375 (58%) did not
      believe that the decision to report to work during a pandemic should be left to
      the individual HCP and 496 (77%) disagreed with the statement that HCP should be
      permanently dismissed for not reporting to work during a pandemic. Only 136 (21%)
      respondents agreed that HCW without children should primarily care for the
      influenza patients. CONCLUSION: Our results suggest that a modest majority of
      HCP, but only a minority of hospital administrators, recognises the obligation to
      treat patients despite the potential risks. Professional ethical guidelines
      allowing for balancing the needs of society with personal risks are needed to
      help HCP fulfil their duties in the case of a pandemic influenza.

PMID- 17192199
TI  - Linkage disequilibrium of evolutionarily conserved regions in the human genome.
AB  - BACKGROUND: The strong linkage disequilibrium (LD) recently found in genic or
      exonic regions of the human genome demonstrated that LD can be increased by
      evolutionary mechanisms that select for functionally important loci. This
      suggests that LD might be stronger in regions conserved among species than in non
      conserved regions, since regions exposed to natural selection tend to be
      conserved. To assess this hypothesis, we used genome-wide polymorphism data from
      the HapMap project and investigated LD within DNA sequences conserved between the
      human and mouse genomes. RESULTS: Unexpectedly, we observed that LD was
      significantly weaker in conserved regions than in non-conserved regions. To
      investigate why, we examined sequence features that may distort the relationship
      between LD and conserved regions. We found that interspersed repeats, and not
      other sequence features, were associated with the weak LD tendency in conserved
      regions. To appropriately understand the relationship between LD and conserved
      regions, we removed the effect of repetitive elements and found that the high
      degree of sequence conservation was strongly associated with strong LD in coding
      regions but not with that in non-coding regions. CONCLUSION: Our work
      demonstrates that the degree of sequence conservation does not simply increase LD
      as predicted by the hypothesis. Rather, it implies that purifying selection
      changes the polymorphic patterns of coding sequences but has little influence on
      the patterns of functional units such as regulatory elements present in non
      coding regions, since the former are generally restricted by the constraint of
      maintaining a functional protein product across multiple exons while the latter
      may exist more as individually isolated units.

PMID- 17192201
TI  - [Ambulatory endocrine surgery].

PMID- 17192200
TI  - An association of a simultaneous nuclear and cytoplasmic localization of Fra-1
      with breast malignancy.
AB  - BACKGROUND: Overexpression of Fra-1 in fibroblasts causes anchorage-independent
      cell growth and oncogenic transformation. A high level of Fra-1 expression is
      found in various tumors and tumorigenic cell lines, suggesting that Fra-1 may be
      involved in malignant progression. This study aimed to investigate the
      significance of Fra-1 expression in breast carcinogenesis. METHODS: The
      expression of Fra-1 was investigated by immunohistochemistry in neoplastic breast
      diseases ranging from benign fibroadenoma to very aggressive undifferentiated
      carcinoma. The correlations of Fra-1 expression with other indicators of breast
      carcinoma prognosis (ER, PR and ErbB2 receptors) were analyzed. RESULTS: All
      neoplastic breast tissues, either benign or malignant breast tissues, were
      nuclear immunoreactive for Fra-1-recognizing antibody. The pattern of Fra-1
      expression by benign neoplastic cells was predominantly nuclear. However, the
      nuclear/cytoplasmic concomitant immunoreactivity was observed in all types of
      breast carcinomas. A clear shift in Fra-1 immunoreactivity, from an exclusively
      nuclear to a simultaneous nuclear and cytoplasmic localization was noticed in
      ~90% of breast carcinomas. CONCLUSION: The overall expression, pattern and
      intensity of Fra-1 proteins were correlated with breast oncogenesis.
      Overexpression of Fra-1, leading to a persistent high cytoplasmic accumulation,
      may play a role in the process of breast carcinogenesis.

PMID- 17192202
TI  - [Ischemic preconditioning of the liver: from molecular bases to clinical
      application].
AB  - Ischemia-reperfusion injury is produced when an organ is deprived of blood flow
      (ischemia), which is then restored (reperfusion). In certain circumstances, this
      injury leads to irreversible organ damage. Several therapeutic strategies have
      been used to reduce the severity of this injury. One of these strategies is the
      application of brief and repetitive episodes of ischemia-reperfusion before
      prolonged ischemia-reperfusion (ischemic preconditioning). In the present article
      we review the molecular mechanisms through which ischemic preconditioning confers
      protection against ischemia-reperfusion injury. The application of ischemic
      preconditioning during liver surgery is discussed, both in normothermic
      situations such as liver resection and in situations of low temperature such as
      liver transplantation.

PMID- 17192203
TI  - [Current technology development for natural orifice transluminal endoscopic
      surgery].
AB  - Natural orifice transluminal endoscopic surgery (NOTES) is a novel concept which
      combines aspects of flexible endoscopy with laparoscopic surgery with the aim of
      creating a new field of patient friendly "incisionless" surgery. This will
      require novel advanced technologies to be developed specifically for NOTES. We
      discuss the technical requirements and the process of creating NOTES
      instrumentation and illustrate the process with some current enabling devices.
      The development process is outlined, including the requirements for NOTES, the
      current technology that can be used, and some prototype devices for access,
      retraction, and tissue approximation. Endoscopes for NOTES must have high
      resolution, large instrument channels, some degree of triangulation, and the
      ability to lock into position inside the abdominal cavity. Instrumentation should
      echo the capabilities of current laparoscopic tools. They should be large and
      sturdy, torque-able, and offer the full spectrum of end-effectors. Finally, NOTES
      technology must permit secure, tailorable tissue approximation. The "R" scope
      from Olympus and the Transport scope from USGI Medical are possible solutions to
      the design requirements for access and visualization. Eagle Claw (Olympus), The
      Swain system (Ethicon), and the G-prox (USGI) are current tissue approximation
      systems under development and investigation in clinical trials. NOTES is a
      potential advance in surgical care. This new approach requires the development of
      new platform devices, tailored to allow the safe and effective practice of this
      advanced endoscopic approach.

PMID- 17192204
TI  - [Influence of quick intraoperative measurements of intact parathyroid hormone in
      the surgical management of primary hyperparathyroidism].
AB  - OBJECTIVE: To evaluate whether a quick parathyroid hormone assay that measures
      intact parathyroid hormone (iPTH) level intraoperatively has modified the
      surgical strategy for primary hyperparathyroidism in the Meixoeiro Hospital in
      Vigo (Pontevedra, Spain). DESIGN: An observational, analytic, historic cohort
      study was performed. Two study groups were established. In group 1 (n = 28) iPTH
      levels were not measured intraoperatively. In group 2 (n = 39) iPTH was measured
      intraoperatively. iPTH was monitored using blood samples from cannulated
      peripheral veins. A positive test was defined as a decrease in iPTH level of >or=
      50% of the baseline preincision level at 10 minutes postexcision, even when the
      baseline value was outside the normal range. The dependent variables evaluated
      were operating time, the number of parathyroid glands visualized, the number of
      parathyroid glands biopsied, length of postoperative hospital stay, unilateral
      exploration, and the percentages of cure, persistence, and recurrence in each
      group. RESULTS: Group 2 showed a statistically significant decrease in operating
      time (144.7 +/- 62.1 versus 178.8 +/- 57.5 minutes; p = 0.025), the number of
      parathyroid glands visualized (1.9 +/- 0.9 versus 2.8 +/- 1.3; p = 0.002), the
      number of parathyroid glands biopsied (1.5 +/- 0.9 versus 2.2 +/- 1.4; p =
      0.025), and the need for bilateral exploration (30.77% versus 85.72%) in
      comparison with group 1. No significant differences were observed in length of
      postoperative hospital stay or in the percentages of cure (94.8% versus 92.85%),
      persistence (5.12% versus 7.14%), and recurrence (2.56% versus 3.57%).
      CONCLUSIONS: In our hospital, intraoperative measurement of iPTH improved the
      surgical strategy of primary hyperparathyroidism and has therefore been included
      in our routine treatment protocol.

PMID- 17192205
TI  - [Organ-preserving resection of the pancreaticoduodenal region in the treatment of
      intraductal papillary mucinous tumors].
AB  - INTRODUCTION: The standard surgical procedure for intraductal papillary mucinous
      neoplasms of the main duct (IPMN-M) or side branch ducts (IPMN-Br) is
      pancreaticoduodenectomy. IPMN-BR is a more indolent disease with a lower
      incidence of malignancy. OBJECTIVE: To evaluate the usefulness of organ
      preserving pancreatic resections (OPPR) including duodenum-preserving pancreatic
      head resection (DPHR) and pancreatic head resection with segmental duodenectomy
      (PHRSD) in patients with IPMN-BR. PATIENTS AND METHOD: Surgical outcomes were
      evaluated in eight IPMN-Br patients: DPHR was performed in 4 patients and PHRSD
      was performed in 4 patients. In addition, 13 IPMN patients with Whipple
      resections were included in the analysis. RESULTS: The incidence of postoperative
      complications was 38% after Whipple resection, 100% after DPHR and 25% after
      PHRSD. The mean length of hospital stay was 27 days after DPHR, 22 days after
      Whipple resection and 16 days after PHRSD. Invasive IPMN was found in 38% of the
      patients in the Whipple group, and noninvasive IPMN was found in 100% of patients
      who underwent organ-preserving surgery. CONCLUSIONS: Pancreaticoduodenectomy
      remains the treatment of choice in patients with invasive IPMN. PHRSD appears to
      be a useful procedure for IPMN-Br located in the head of the pancreas.

PMID- 17192207
TI  - [National project for the clinical management of healthcare processes. The
      surgical treatment of cholelithiasis. Development of a clinical pathway].
AB  - INTRODUCTION: Because surgical treatment of gallstones is highly prevalent, this
      topic is particularly suitable for a national study aimed at determining the most
      important indicators and developing a clinical pathway. OBJECTIVES: To analyze
      the results obtained during the hospital phase of the process. To define the key
      indicators of the process. To design a clinical pathway for laparoscopic
      cholecystectomy. PATIENTS AND METHODS: A multicenter, prospective, cross
      sectional, descriptive study was performed of patients who consecutively
      underwent surgery for gallstones in 2002. The sample size calculated with data
      provided by the National Institute of Statistics was 304 patients, which was
      increased by 45% to compensate for possible losses. Inclusion criteria consisted
      of elective cholecystectomy for gallstones, without preoperative findings
      suggestive of common duct stones. A database was designed (Microsoft Access 2000)
      with 76 variables analyzed in each patient. RESULTS: Completed questionnaires
      were obtained from 37 hospitals with 426 patients. The mean age was 55.69 years,
      with a predominance of women (68.3%). The most frequent symptom was biliary colic
      (23%). A total of 20.3% of the patient had prior episodes of cholecystitis and
      18% had a history of mild pancreatitis. Diagnosis was given by ultrasonography in
      93.2% of the patients. Informed consent was provided by 93.2%. The intervention
      was performed on an inpatient basis in 96.1% and in the ambulatory setting in the
      remainder. Antibiotic and antithrombotic prophylaxis was administered in 78.9%
      and 75.1% of the patients respectively. The laparoscopic approach was used in
      84.6%, with a conversion rate of 4.9%. Intraoperative cholangiography was
      performed in 17.8% of the patients and common duct stones were found in 7
      patients. The most frequent complication was surgical wound infection (1.1%).
      Possible accidental lesion of the biliary tract occurred in 0.7% of the patients
      and was described as biliary fistula. There were four reinterventions: biliary
      fistula (1), hemoperitoneum (2) and cause unknown (1). The mean surgical time was
      73.17 minutes, with a median of 60 minutes. Postoperative length of stay was 4.75
      days in open surgery and 2.67 days in laparoscopic surgery. Ninety-nine percent
      of the patients were satisfied or highly satisfied with the healthcare received.
      CONCLUSIONS: Analysis of the process and review of the literature identified a
      series of areas requiring improvement, which were gathered in the clinical
      pathway developed. These areas consisted of increasing the number of patients
      with correctly indicated antibiotic and antithrombotic prophylaxis, increasing
      the percentage of patients providing informed consent and undergoing adequate
      preoperative tests, limiting intraoperative cholangiography to selected patients,
      and reducing the number of patients with an overall stay of 3 days.

PMID- 17192206
TI  - [Modifications in intact parathyroid hormone, total serum calcium, and ionized
      calcium levels in the surgery of primary hyperparathyroidism for single adenoma].
AB  - INTRODUCTION: We evaluated total serum calcium (TSC) and ionized calcium (IC) and
      their correlation with intraoperative intact parathyroid hormone (iPTH) in the
      surgery of primary hyperparathyroidism in patients with a single adenoma.
      MATERIAL AND METHOD: We performed a prospective, blind trial with determination
      of iPHT, TSC and IC in a cohort of surgical patients (n = 279; 244 were valid for
      the study) who underwent surgery in the Department of Surgery, Hospital de
      Cruces, between October 1999 and April 2006. Total calcium, ionic calcium and
      iPTH were measured in the outpatient department, on admission and
      intraoperatively (at anesthesia induction and every 5 minutes after surgical
      excision). RESULTS: Levels of calcium and iPTH were corrected in 234 (95.9%)
      patients. iPTH decreased from abnormal preoperative values of 294.43 +/- 286.38
      pg/ml to 97.89 +/- 121.01 mg/dl (minute 5), 58.58 +/- 58.37 pg/ml (minute 10),
      44.62 +/- 54.77 pg/ml (minute 15), and 38.42 +/- 51.72 pg/ml (minute 20). TSC
      decreased from preoperative values of 10.93 +/- 1.04 mg/dl to 10.2 +/- 0.97 mg/dl
      (minute 5), 10.17 +/- 1.00 mg/dl (minute 10), 10.12 +/- 0.98 mg/ml (minute 15),
      and 10.09 +/- 1.03 mg/ml (minute 20). The results for ionized calcium were as
      follows: 4.90 +/- 0.63 mg/dl at induction, 4.84 +/- 0.61 mg/dl (minute 5), 4.84
      +/- 0.66 mg/dl (minute 10), 4.82 +/- 0.63 mg/dl (minute 15), and 4.82 +/- 0.63
      mg/dl (minute 20). Frozen samples were conclusive for parathyroid tissue (19.56
      +/- 15.3 after excision). CONCLUSIONS: Intraoperative total calcium levels may
      help to predict adequate elimination of parathyroid tissue in primary
      hyperparathyroidism when intraoperative iPTH is not available. Ionized calcium
      levels did not show the same decrease.

PMID- 17192208
TI  - [Right hepatectomy and left hepatectomy performed via hand-assisted laparoscopic
      surgery. Description of an original technique].
AB  - INTRODUCTION: Laparoscopic liver surgery in solid tumors presents a number of
      difficulties. This type of surgery is indicated especially in tumors of less than
      5 cm located in the left lobe and in anterior segments of the right lobe. Access
      to posterior lesions of the right lobe (segments VII and VIII) and performing
      major regulated hepatectomies (more than 3 segments) are at present difficult for
      liver surgeons. OBJECTIVE: To present a regulated right hepatectomy (RH) and left
      hepatectomy (LH) performed via hand-assisted laparoscopic surgery (HALS) using an
      original technique. PATIENTS AND METHOD: RH was performed in a 70-year-old man
      with hepatic metastases from colorectal carcinoma (pT2N0M1 sigmoid
      adenocarcinoma). LH was performed in a 44-year-old woman with a 16-cm hemangioma
      that had shown tumoral growth. Dissection of the hepatic artery was performed
      between ligations, and the portal vein was sectioned between ligations or with a
      vascular endostapler. Division of the bile duct and suprahepatic veins was
      performed with a vascular endostapler. Parenchymal dissection was carried out
      with a harmonic scalpel and dissection of intrahepatic veins of over 3 mm was
      performed with a 10-mm Ligasure Atlas. RESULTS: The operating time for RH was 360
      min, with no transfusion or complications, and length of hospital stay was 5
      days. The operating time for LH was 240 min, requiring 2 U of blood, with no
      morbidity and a length of hospital stay of 4 days. CONCLUSIONS: HALS allows major
      liver resections to be performed with low morbidity and mortality and with the
      advantages of laparoscopic surgery.

PMID- 17192209
TI  - [Spontaneous pneumomediastinum mimicking Boerhaave's syndrome].
AB  - Spontaneous pneumomediastinum is an uncommon benign disorder that usually occurs
      in young men. Because of its clinical features and physiopathologic mechanism,
      other, more serious disorders that could require urgent treatment, such as
      Boerhaave's syndrome or spontaneous esophageal rupture, must be ruled out. We
      report the case of a 19-year-old man with no relevant history, who presented
      mediastinal emphysema after an episode of repeated vomiting in the context of
      alcohol abuse. Imaging techniques help to assess esophageal involvement.

PMID- 17192210
TI  - [Retrorectal tumors in adults. Experience in five cases].
AB  - The most frequent tumors that grow in the retrorectal space are embryological.
      Their management requires adequate knowledge of the characteristics of these
      lesions. We present five cases of retrorectal tumors.

PMID- 17192211
TI  - [Giant esophageal lipoma].
AB  - Esophageal lipomas are uncommon benign tumors. The main symptom of this type of
      tumor is dysphagia due to esophageal obstruction. The diagnostic studies of
      choice are endoscopy, radiological investigation with contrast administration,
      computed tomography, and echoendoscopy. We present an unusual case of giant
      pediculated esophageal lipoma which manifested clinically with dysphagia.
      Management was surgical.

PMID- 17192212
TI  - [Common bile duct cyst in adults].

PMID- 17192213
TI  - [Laparoscopic treatment of primary splenic cyst].

PMID- 17192214
TI  - [Nephrobronchial fistula secondary to chronic xanthogranulomatous pyelonephritis
      as a cause of pulmonary abscess and persistent hemoptysis].

PMID- 17192215
TI  - [Comparison of surgical results: minimum standardization, please].

PMID- 17192216
TI  - [The Serra-Doria technique. A good resource for the treatment of recurrent
      achalasia].

PMID- 17192217
TI  - [Advanced trauma life support: 25 years' experience].

PMID- 17192218
TI  - [Complications of surgical resection of esophageal cancer].
AB  - Esophageal resection has undergone refinements over recent years, with improved
      outcomes. However, in-hospital mortality remains above 10% in developed countries
      and is below 5% in only a select group of hospitals. Morbidity remains high even
      in high-volume hospitals. We reviewed risk factors in esophageal resection.
      Pulmonary complications occur mainly in older patients and in those with
      pulmonary dysfunction, especially %FEV1 or hypoxia. Liver cirrhosis, squamous
      cell cancer, low patient volume, and cervical anastomoses also increase
      complication rates. Neoadjuvant chemoradiotherapy, which may be effective in
      squamous cell tumors, can also increase morbidity. The main cause of morbidity
      and mortality are pleuropulmonary complications. Also significant are anastomotic
      leak and esophageal conduit necrosis. A complex procedure such as esophageal
      resection is better served in specialized teams.

PMID- 17192219
TI  - [Fast-track multimodal rehabilitation programs in laparoscopic colorectal
      surgery].
AB  - For the last two decades, general and digestive surgeons have attempted to
      improve the postoperative course of surgical patients. Classical perioperative
      treatment can be described as a period of preoperative dehydration caused by
      fasting and intensive colon preparation followed by fluid overload generally due
      to excessively prolonged serum therapy. There is also perioperative surgical
      stress, the trauma of surgery itself, and a long period of drainage and
      nasogastric tubes. The patient is thus literally confined to bed and mobilization
      is, at the very least, difficult. Moreover, the use of opiates delays intestinal
      peristalsis and consequently oral nutrition. All together, these factors prolong
      the length of hospital stay and hamper recovery. All these perioperative
      treatment modalities have been questioned by Kehlet, resulting in a set of new,
      more realistic and evidence-based modalities, currently known as the fast-track
      program. The aim of this program is to decrease perioperative stress, reduce
      organ involvement produced by surgical trauma and hasten the patient's general
      recovery. Major advantages of this program consist not only of shorter length of
      hospital stay but also of a concurrent improvement in patients' quality of life
      and a reduction in mortality. The present review article analyzes all these
      modalities, with special emphasis on laparoscopic colorectal surgery. This
      approach is presented as one of the elements of the fast-track program.

PMID- 17192221
TI  - [Results of defunctionalized jejunal loop after pancreaticoduodenectomy].
AB  - INTRODUCTION: Anastomotic leak continues to be a common cause of complications
      after pancreaticoduodenectomy. Numerous surgical techniques have been described
      to avoid this complication. OBJECTIVE: We evaluated the use of a defunctionalized
      jejunal loop for the pancreas after pancreaticoduodenectomy. MATERIAL AND
      METHODS: Between 1991 and 2005, the findings in 80 patients were analyzed in this
      prospective study of the use of a defunctionalized jejunal loop for the pancreas
      as a reconstructive procedure following pancreaticoduodenectomy. All the patients
      were operated on by two surgeons. The following clinical variables were recorded:
      age, sex, diameter of the main pancreatic duct, pancreas texture, operating time,
      intraoperative blood transfusion, mean length of hospital stay, and operative
      mortality. Seven complications were defined: anastomotic leakage (biliary and
      duodenal), pancreatic fistula, abscess, sepsis, bleeding, delayed gastric
      emptying, and postoperative pancreatitis. Four different definitions were used
      for pancreatic fistula. RESULTS: Of the 80 patients, 16 (20%) developed
      pancreatic fistula according to at least one of the criteria used. Pancreatic
      fistula was more frequent in patients with a small duct (33.3%), and soft
      pancreatic texture (29%), and was the cause of 100% of intraabdominal
      hemorrhages, 80% of abdominal abscesses, and 60% of mortality. The mean length of
      hospital stay was 20.6 days and the mortality rate was 6.6% (5/80). During follow
      up two patients developed pancreatitis. CONCLUSION: After
      pancreaticoduodenectomy, reconstruction with a defunctionalized jejunal loop for
      the pancreas is a safe and effective technique.

PMID- 17192220
TI  - [Applicability, safety and efficacy of an ambulatory treatment protocol in
      patients with uncomplicated acute diverticulitis].
AB  - INTRODUCTION: The aim of this study was to evaluate the applicability, safety and
      efficacy of an ambulatory treatment protocol in patients with uncomplicated acute
      diverticulitis. PATIENTS AND METHODS: All patients diagnosed with uncomplicated
      acute diverticulitis based on abdominal computed tomography findings during a 2
      year period were prospectively included. Patients with vomiting, severe
      comorbidities, or without an appropriate family environment were excluded.
      Ambulatory treatment consisted of oral antibiotics for 1 week (amoxicillin
      clavulanic 1 g t.i.d. or ciprofloxacin 500 mg b.i.d. plus metronidazole 500 mg
      t.i.d. in patients with penicillin allergy). A clear liquid diet for the first 2
      days and pain control with oral acetaminophen 1 g t.i.d. were also recommended.
      RESULTS: Fifty-three patients were diagnosed with uncomplicated acute
      diverticulitis and 13 patients were excluded. Therefore, ambulatory treatment was
      initiated in 40 patients. Only two patients (5%) required admission after
      outpatient therapy was started due to vomiting and persistent abdominal pain,
      respectively. In both patients, the inflammatory process was successfully
      resolved by intravenous antibiotic treatment. In the remaining 38 patients (95%),
      ambulatory treatment was completed without complications. CONCLUSIONS: Ambulatory
      treatment of uncomplicated acute diverticulitis is safe, effective and applicable
      in most patients with tolerance to oral intake and with an appropriate family
      environment.

PMID- 17192222
TI  - [Utility of methoxy isobutyl isonitrile (MIBI) scintigraphy, ultrasound and
      computerized axial tomography in preoperative topographic diagnosis of
      hiperparathyroidism].
AB  - OBJECTIVES: 1. To assess the sensitivity of scintigraphy using methoxy isobutyl
      isonitrile (MIBI). 2. To compare its resolution with that of ultrasound (US) and
      computerized axial tomography (CAT). 3. To use its diagnostic reliability to
      determine whether selective approaches can be used to treat hyperparathyroidism
      (HPT). PATIENTS AND METHOD: A study of 76 patients who underwent surgery for HPT
      between 1996 and 2005 was performed. MIBI scintigraphy and cervical US were used
      for whole-body scanning in all patients; CAT was used in 47 patients.
      Intraoperative and postoperative biopsies were used for final evaluation of the
      tests, after visualization and surgical extirpation. RESULTS: The results of
      scintigraphy were positive in 65 patients (85.52%). The diagnosis was correct in
      all of the single images. Multiple images were due to hyperplasia and parathyroid
      adenomas with thyroid disease (5.2%). Three images, incorrectly classified as
      negative (3.94%), were positive. The sensitivity of US was 63% and allowed
      detection of three MIBI-negative adenomas (4%). CAT was less sensitive (55%), but
      detected a further three MIBI-negative adenomas (4%). CONCLUSIONS: 1. The
      sensitivity of MIBI reached 89.46%. In the absence of thyroid nodules, MIBI
      diagnosed 100% of single lesions. Pathological thyroid processes produced false
      positive results (5.2%) and there were diagnostic errors (4%). 2. MIBI
      scintigraphy was more sensitive than US and CAT. 3. Positive, single image
      scintigraphy allows a selective cervical approach. US and CAT may help to save a
      further 8% of patients (with negative scintigraphy).

PMID- 17192223
TI  - [Integral management of the process of laparoscopic cholecystectomy].
AB  - INTRODUCTION: One of the most important objectives of public healthcare services
      is to guarantee integral healthcare to patients; activity is currently focussed
      on process management. Analysis of a "key" process could have health, social and
      economic effects if measures to improve the results are designed. The aim of the
      present study was to evaluate the process of laparoscopic cholecystectomy in our
      hospital in order to determine its strong and weak points. MATERIAL AND METHOD:
      We performed a prospective observational study of the laparoscopic
      cholecystectomy (LC) process in the Jarrio Hospital between January 2001 and
      December 2002. A working group was formed and a process flowchart was designed by
      consensus. The different steps of the process were evaluated through the main
      indicators of quality: accessibility, efficiency, and effectiveness, including
      cost, the convalescence period, and patient satisfaction. The results were
      compared with the standards defined by the Andalusian Health Council,
      bibliographic sources, and hospital commissions. The statistical analysis was
      performed with 95% confidence intervals of the main results. RESULTS: A series of
      86 patients who underwent LC was evaluated. The results for accessibility showed
      wide variability in delays for specialist consultations, the waiting list for
      surgery, and urgent diagnostic tests, often exceeding the standards. The
      laparoscopic approach was more frequent than open cholecystectomy; morbidity and
      mortality with LC were below the reference standards and compliance with
      established prophylaxis protocols was close. The efficiency markers showed that
      the length of hospital stay for elective LC was close to the standard; however,
      for cholecystitis preoperative length of stay was longer than the standard.
      Overall patient satisfaction with medical care and non-medical services was high.
      CONCLUSIONS: Quality analysis of a process allowed us to identify strong points
      such as the high rate of laparoscopic cholecystectomy -showing good effectiveness
      and efficiency- the quality of informed consent, and patient satisfaction.
      Required improvements consisted of shortening preoperative length of stay in
      acute cholecystitis and waiting lists, informing patients about the length of the
      convalesce period, eliminating routine type and screen, and admitting patients on
      the day of surgery.

PMID- 17192224
TI  - [The POSSUM scoring system: an instrument for measuring quality in surgical
      patients].
AB  - INTRODUCTION: The POSSUM scale (Physiological and Operative Severity Score for
      the enUmeration of Mortality and Morbidity) is a scoring system that is used to
      predict risk-adjusted mortality and morbidity rates in a wide variety of surgical
      procedures. In this prospective study, the validity of the POSSUM scale was
      evaluated in patients undergoing laparotomy in a general surgery department.
      PATIENTS AND METHODS: The POSSUM scale was prospectively applied in all patients
      undergoing elective and emergency laparotomy in the general surgery department of
      a level II hospital over 8 months. A total of 105 patients were included, of
      which 24 underwent emergency laparotomy and 81 underwent elective surgery.
      Predicted mortality and morbidity rates were calculated by using the POSSUM
      scale. These results were compared with actual outcomes by using Fisher's test.
      RESULTS: The mean physiological score was 23.4 points (range: 12-40 points),
      while the mean surgical score was 11.3 points (range: 6-24 points). Three
      patients died during the postoperative period and 47 had morbidity. When the
      observed results for mortality were compared with those predicted by the POSSUM
      scoring system, no significant differences were observed in the analysis by risk
      groups, except in the risk group < 20 %, in which the POSSUM scale overestimated
      mortality. The risk of morbidity was underestimated by the POSSUM scale in the
      risk group < 20 %. CONCLUSION: The POSSUM scoring system is a useful predictor of
      morbidity and mortality in patients undergoing emergency and elective laparotomy.

PMID- 17192225
TI  - [Bilateral Chylothorax after delivery: an infrequent case treated with
      videothoracoscopic talc pleurodesis].
AB  - Bilateral chylothorax after delivery is a highly infrequent entity. We present
      the case of a 28-year-old woman who developed progressive dyspnea due to
      bilateral milky pleural effusion several months after delivery. The effusion was
      found to contain chylomicrons in the biochemical analysis. Initial conservative
      treatment failed twice and the chylothorax was successfully treated through
      sequential bilateral videothoracoscopy with an interval of 6 days between the two
      interventions and pleurodesis with spray talc.

PMID- 17192226
TI  - [Treatment of severe chronic constipation through the antegrade continent enema
      procedure].
AB  - The antegrade continent enema procedure was first described in 1990 by Malone for
      the treatment of severe fecal neurogenic incontinence in children. Since then,
      this technique has been successfully carried out in adults, as well as in
      patients with refractory constipation. The procedure provides a continent and
      catheterizable channel, generally an appendicostomy, through which antegrade
      washouts are given to produce colonic emptying. We describe the case of a 23-year
      old man with severe constipation and overflow fecal incontinence who underwent an
      appendicostomy. There were no immediate postoperative complications and saline
      washouts were started on the fourth day. Since then, the patient has had a bowel
      movement between 1 and 3 hours after each washout, has recovered continence, and
      no longer wears an absorbent pad.

PMID- 17192227
TI  - [Laparoscopic splenectomy due to torsion of a wandering spleen].
AB  - Wandering spleen is an uncommon entity, characterized by the anomalous position
      of the spleen, caused by the absence or laxity of its suspensory ligaments. The
      most common symptoms are usually due to intermittent or complete torsion of the
      splenic pedicle with subsequent infarction. We report a case of torsion of a
      wandering spleen. Laparoscopic splenectomy was performed and recovery was
      uneventful. Although few cases of wandering spleen treated laparoscopically have
      been reported in the literature, laparoscopy has been demonstrated to be a safe
      technique for the treatment of this entity.

PMID- 17192228
TI  - [Scrotal cystocele].

PMID- 17192229
TI  - [More on the sentinel node and methodology for its analysis].

PMID- 17192230
TI  - [Central pontine myelinolysis after liver transplantation].

PMID- 17192231
TI  - [Hepatocellular carcinoma: atypical presentation].

PMID- 17192232
TI  - [Surgical emergency in patients with polytrauma without the possibility of
      transfusion for religious reasons].

PMID- 17192233
TI  - Abstracts of the 11th Annual European Meeting on the Neurogenetics of Drosophila.
      September 2-6, 2006. Leuven, Belgium.

PMID- 17192234
TI  - Abstracts from the Tenth Annual Society for Cardiovascular Magnetic Resonance
      (SCMR) Scientific Sessions and the Sixth Meeting of the Euro CMR Working Group.
      February 2-4, 2007. Rome, Italy.

PMID- 17192246
TI  - Implantable biodegradable sponges: effect of interpolymer complex formation of
      chitosan with gelatin on the release behavior of tramadol hydrochloride.
AB  - The effect of interpolymer complex formation between positively charged chitosan
      and negatively charged gelatin (Type B) on the release behavior of tramadol
      hydrochloride from biodegradable chitosan-gelatin sponges was studied. Mixed
      sponges were prepared by freeze-drying the cross-linked homogenous stable foams
      produced from chitosan and gelatin solutions where gelatin acts as a foam
      builder. Generation of stable foams was optimized where concentration, pH of
      gelatin solution, temperature, speed and duration of whipping process, and,
      chitosan-gelatin ratio drastically affect the properties and the stability of the
      produced foams. The prepared sponges were evaluated for their morphology, drug
      content, and microstructure using scanning electron microscopy, mechanical
      properties, uptake capacity, drug release profile, and their pharmacodynamic
      activity in terms of the analgesic effect after implantation in Wistar rats. It
      was revealed that whipping 7% (w/w) gelatin solution, of pH 5.5, for 15 min at 25
      degrees C with a stirring speed of 1000 rpm was the optimum conditions for stable
      gelatin foam generation. Moreover, homogenous, uniform chitosan-gelatin foam with
      small air bubbles were produced by mixing 2.5% w/w chitosan solution with 7% w/w
      gelatin solution in 1:5 ratio. Indeed, polyionic complexation between chitosan
      and gelatin overcame the drawbacks of chitosan sponge mechanical properties
      where, pliable, soft, and compressible sponge with high fluid uptake capacity was
      produced at 25 degrees C and 65% relative humidity without any added plasticizer.
      Drug release studies showed a successful retardation of the incorporated drug
      where the t50% values of the dissolution profiles were 0.55, 3.03, and 4.73 hr
      for cross-linked gelatin, un-cross-linked chitosan-gelatin, and cross-linked
      chitosan-gelatin sponges, respectively. All the release experiments followed
      Higuchi's diffusion mechanism over 12 hr. The achieved drug prolongation was a
      result of a combined effect of both cross-linking and polyelectrolyte
      complexation between chitosan and gelatin. The analgesic activity of the
      implanted tramadol hydrochloride mixed chitosan-gelatin sponge showed reasonable
      analgesic effect that was maintained for more than 8 hr. Therefore, the use of
      chitosan and gelatin together appears to allow the formulator to manipulate both
      the drug release profiles and the mechanical properties of the sponge that could
      be effectively implanted.

PMID- 17192247
TI  - Preparation and evaluation of pranoprofen gel for percutaneous administration.
AB  - The percutaneous delivery of nonsteroidal anti-inflammatory drug (NSAID) has the
      advantages of avoiding the hepatic first pass effect and delivering the drug to
      the inflammation site at a sustained, concentrated level over an extended period
      of time. Hydroxypropyl methylcellulose (HPMC) and poloxamer 407 were used in an
      attempt to develop new topical formulations of pranoprofen. The effects of the
      drug concentration (0.04, 0.08, 0.12, 0.16, and 0.20%) on the rate of drug
      release from HPMC-poloxamer 407 gels were examined using a synthetic cellulose
      membrane at 37+/-0.5 degrees C. The rate of drug permeation increased
      significantly with increasing drug concentration in the gels until the
      concentration reached 0.16%, and increased slightly thereafter. The effects of
      temperature on the rate of drug release from the 0.16% pranoprofen gels were
      evaluated at 32, 37, and 42 degrees C. The rate of drug release from the 0.16%
      pranoprofen gels increased with increasing temperature with activation energy
      (Ea) of 8.88 kcal/mol. Various penetration enhancers, such as nonionic
      surfactants and fatty acids, were incorporated in the gel formulation in an
      attempt to increase the level of drug permeation. Among the enhancers used,
      octanoic acid had the strongest enhancing effects with an enhancement factor of
      3.09. The anti-inflammatory effect of the pranoprofen gel was evaluated using a
      rat paw-edema model. The 0.16% pranoprofen gel containing octanoic acid as an
      enhancer reduced the edema size by approximately 73% compared with that of the
      control group. These results highlight the feasibility of a topical gel
      formulation of pranoprofen containing an enhancer.

PMID- 17192248
TI  - Hard gelatin and hypromellose (HPMC) capsules: estimation of rupture time by real
      time dissolution spectroscopy.
AB  - The objective of this study was to measure rupture time of gelatin and
      hypromellose (hydroxypropyl methylcellulose or HPMC) capsules using a novel
      approach based on real-time dissolution spectroscopy. Rupture time was measured
      in standard dissolution apparatus at a constant temperature using a dip-type
      fiber-optic probe. Labrasol released from the capsules was treated as the marker
      of the rupture process. Light scatter generated by the emulsified labrasol was
      detected by an ultrafast monochromator at scan rates approximating 24,000 nm/min.
      This technique was validated by measuring the dissolution time of gelatin
      capsules. Rupture times of hypromellose capsules were studied as a function of
      capsule size, capsule grade, and dissolution medium. Statistical correlations
      were analyzed by ANOVA. Rupture time of hypromellose capsules was dependent on
      both the medium and the grade of the capsule, and was independent of capsule
      size. The composition of the dissolution medium contributes to the rupture time
      of the capsules and should be considered when fast release and quick biological
      response is desired. Release delay, however, may not manifest itself in vivo and
      the time to maximum plasma concentration may not be significant.

PMID- 17192249
TI  - The effect of rubber closures on the haze state of ceftriaxone sodium for
      injection.
AB  - The migration of volatile components into the headspace of glass vials from
      rubber closures is a potential source of haze formation in reconstituted
      solutions of powders for parenteral administration. In this paper, a headspace
      method was used to extract volatile substances from different types of rubber
      closures used in ceftriaxone sodium for injection whose clarity were poor. The
      extracts obtained were analyzed by gas chromatography (GC)-mass spectrometry
      (MS). An antioxidant in rubber closures, butylated hydroxytoluene (BHT), was
      found to affect the haze state of ceftriaxone sodium for injection.

PMID- 17192250
TI  - Preparation and characterization of solid dispersions of piroxicam with
      hydrophilic carriers.
AB  - The objective of this study was to improve the dissolution rate of a poor water
      soluble drug, piroxicam, by solid dispersion technique. Solid dispersions were
      prepared by three different methods depending on the type of carrier. The
      dissolution rate of piroxicam was markedly increased in solid dispersion of myrj
      52, Eudragit E100 and mannitol. Solubility studies revealed a marked increase in
      the solubility of piroxicam with an increase in myrj 52 and Eudragit E100
      concentrations. Data from the X-ray diffraction and FT-IR spectroscopy showed
      that piroxicam was amorphous in the solid dispersions prepared with dextrin and
      Eudragit E100.

PMID- 17192251
TI  - Polymer membrane electrodes for sensitive potentiometric determination of beta
      blockers.
AB  - The construction of PVC matrix-type beta-blockers (sotalol, carvedilol, and
      betaxolol) ion selective electrodes and their use for direct potentiometry of
      their respective species are described. The proposed sensors are based on the
      complex ion associates of beta-blockers with tungstophosphate (TP) and Ammonium
      Reineckate (Rein) ionophoris in poly vinyl chloride membrane (PVC) with
      Dioctylphthalate (DOP) plasticizer. The four electrodes (Beta-TP), (Sota-TP),
      (Carve-TP), and (Cave-Rein) show stable potential response with near Nernstian
      slope of 50.8, 33.7, 32.35, and 33 mv per decade, range of concentration 10-2-10
      7 M beta-blockers. Selectivity coefficients data obtained for 11 different
      organic and inorganic ions are presented. The electrodes have fast response time
      (30 and 40 s) and were used over wide range of pH 4.5-8.5. Validation of the
      method according to the quality assurance standers shows suitability of proposed
      sensors for use in the quality control assessment of these drugs. The results
      obtained for the determination of beta-blockers with the proposed electrodes show
      average recoveries of 100.78% and a mean standard deviation of +/-1.2. The
      nominal are obtained. The data agree well with those obtained by standard
      methods.

PMID- 17192252
TI  - Kinetic analysis of chlorpropamide dissolution from solid dispersions.
AB  - Solid dispersions (SDs) of chlorpropamide were prepared by the solvent deposition
      technique using two grades of microcrystalline cellulose as carrier materials
      with different ratios of drug to carrier. The dissolution rate of chlorpropmide
      from the SDs was carried out at two physiological pH values of 1.1 and 7.25
      simulating gastric and intestinal environments. The dissolution was dependent on
      the grade, the ratio of drug to carrier and pH. The higher dissolution was
      observed for more hydrophilic grade of the carrier as well as the higher ratio of
      carrier to drug. At the higher pH the drug dissolved much faster than the lower
      pH. X-ray diffraction showed some reduced drug crystallinity in SDs whereas
      infrared spectroscopy revealed no drug interactions with solvent and the
      carriers. The enhanced dissolution was attributed to the reduced drug
      crystallinity, decreased particle size, increased wettability and reduced
      aggregation of the hydrophobic drug particles. A novel model denoted as
      reciprocal powered time model with its theoretical justification was employed to
      analyze the dissolution data and proved to be superior to commonly used models
      for the analysis of the data. There was a quantitative relation between the model
      parameter and the ratio of carrier to drug which could be of value in dissolution
      rate prediction.

PMID- 17192253
TI  - Transport characteristics of a beta sheet breaker peptide across excised bovine
      nasal mucosa.
AB  - The purpose of the present study was to investigate the permeation
      characteristics of the beta sheet breaker peptide AS 602704 (BSB) on excised
      bovine nasal mucosa using an Ussing chamber model. The influence of various
      absorption enhancers such as sodium cholate, sodium dodecyl sulfate (SDS),
      cetrimidum, sodium caprate, Na(2)EDTA, polycarbophil (PCP), the thiomer conjugate
      polycarbophil-cysteine (PCP-Cys), and poly-l-arginine (poly-l-arg; 100 kDa) was
      evaluated. Additionally, the influence of temperature and pH on the transport
      rate as well as the stability of the peptide drug against enzymatic degradation
      were investigated in vitro. The effective permeability coefficient (P(eff)) of
      BSB in Krebs-Ringer-buffer (KRB) pH 7.4 was (1.89 +/- 0.44)* 10-5, while in the
      presence of sodium caprate (0.5%) a P(eff) of (9.58 +/- 1.82)*10-5 was achieved.
      Rank order of enhancement ratio was sodium caprate > SDS > sodium cholate >
      Na(2)EDTA > poly-L-arg = PCP-Cys. In case of cetrimidum and PCP even a decrease
      in the absorption of BSB was determined. Na2EDTA reduced the enzymatic
      degradation of BSB when exposed to a nasal tissue homogenate by more than the
      half. An increased lipophilicity of BSB because of a more acidic milieu (pH 5.5)
      did not lead to an increased transcellular transport. Permeation studies carried
      out at 4 degrees C compared to 37 degrees C demonstrated a temperature dependent
      permeation behaviour suggesting an additional active carrier mediated transport.
      The results obtained within these studies should facilitate the development of a
      nasal delivery system for AS 602704 for the treatment of Alzheimer's disease.

PMID- 17192254
TI  - Evaluation and controlled release characteristics of modified xanthan films for
      transdermal delivery of atenolol.
AB  - The present study was performed to evaluate the possibility of using modified
      xanthan films as a matrix system for transdermal delivery of atenolol (ATL),
      which is an antihypertensive drug. Acrylamide was grafted onto xanthan gum (XG)
      by free radical polymerization using ceric ion as an initiator. Fourier transform
      infrared spectroscopy and differential scanning calorimetry indicated the
      formation of the graft copolymer. The obtained graft copolymer was loaded with
      ATL and films were fabricated by solution casting method for transdermal
      application. Various formulations were prepared by varying the grafting ratio,
      drug loading, and different penetration enhancers. The formulations prepared were
      characterized for weight, thickness uniformity, water vapor transmission rate,
      and uniformity in drug content of the matrix. All the thin films were slightly
      opaque, smooth, flexible, and permeable to water vapor, indicating their
      permeability characteristics suitable for transdermal studies. Fourier transform
      infrared spectroscopy and differential scanning calorimetry studies indicated no
      significant interactions between drug and polymer. Drug is distributed uniformly
      in the matrix but showed a slight amorphous nature. Drug-loaded films were
      analyzed by X-ray diffraction to understand the drug polymorphism inside the
      films. Scanning electron microscopic studies of the placebo and drug-loaded films
      demonstrated a remarkable change in their surface morphology. The skin irritation
      tests were performed in mice and these results suggested that both placebo and
      drug-loaded films produced negligible erythema and edema compared to formalin
      (0.8% v/v) as the standard irritant. The in vitro drug release studies were
      performed in phosphate buffer saline using a Keshary-Chien diffusion cell.
      Different formulations were prepared and variations in drug release profiles were
      observed. Release data were analyzed by using the Ritger and Peppas equation to
      understand the mechanism of drug release as well as the estimation of n values,
      which ranged between 0.41 and 0.53, suggesting a Fickian diffusion trend.

PMID- 17192255
TI  - The use of organic vapor sorption to determine low levels of amorphous content in
      processed pharmaceutical powders.
AB  - Organic dynamic vapor sorption (organic-DVS) was used to characterize amorphous
      content in known amorphous-crystalline mixtures of lactose and salbutamol
      sulfate. N-octane was chosen as an apolar probe and measurements were carried out
      by exposing mixtures of each sample to partial pressures 0-90% p/p(0). A linear
      relationship between amorphous content and n-octane partial pressure was observed
      for both lactose and salbutamol sulfate with R(2) values of 0.992 and 0.999,
      respectively. In addition, the influence of sequential mechanical processing in a
      ball mill on the amorphous content in crystalline lactose was investigated.
      Cumulative milling times resulted in an exponential increase in amorphous content
      (using the linear relationship obtained for lactose), with a maximum amorphous
      content of 14% being induced after 60 min milling. In comparison, analysis of the
      60 min mill time samples after exposure to 85% relative humidity suggested 0.00%
      amorphous content.

PMID- 17192257
TI  - Proteomics analysis of protein kinases by target class-selective prefractionation
      and tandem mass spectrometry.
AB  - Protein kinases constitute a large superfamily of enzymes with key regulatory
      functions in nearly all signal transmission processes of eukaryotic cells.
      However, due to their relatively low abundance compared with the vast majority of
      cellular proteins, currently available proteomics techniques do not permit the
      comprehensive biochemical characterization of protein kinases. To address these
      limitations, we have developed a prefractionation strategy that uses a
      combination of immobilized low molecular weight inhibitors for the selective
      affinity capture of protein kinases. This approach resulted in the direct
      purification of cell type-specific sets of expressed protein kinases, and more
      than 140 different members of this enzyme family could be detected by LC-MS/MS.
      Furthermore the enrichment technique combined with phosphopeptide fractionation
      led to the identification of more than 200 different phosphorylation sites on
      protein kinases, which often remain occluded in global phosphoproteome analysis.
      As the phosphorylation states of protein kinases can provide a readout for the
      signaling activities within a cellular system, kinase-selective phosphoproteomics
      based on the procedures described here has the potential to become an important
      tool in signal transduction analysis.

PMID- 17192259
TI  - Cores and pH-dependent dynamics of ferredoxin-NADP+ reductase revealed by
      hydrogen/deuterium exchange.
AB  - NMR-detected hydrogen/deuterium (H/D) exchange of amide protons is a powerful way
      for investigating the residue-based conformational stability and dynamics of
      proteins in solution. Maize ferredoxin-NADP(+) reductase (FNR) is a relatively
      large protein with 314 amino acid residues, consisting of flavin adenine
      dinucleotide (FAD) and nicotinamide adenine dinucleotide phosphate (NADP(+))
      binding domains. To address the structural stability and dynamics of FNR, H/D
      exchange of amide protons was performed using heteronuclear NMR at pD(r) values
      8.0 and 6.0, physiologically relevant conditions mimicking inside of
      chloroplasts. At both pD(r) values, the exchange rate varied widely depending on
      the residues. The profiles of protected residues revealed that the highly
      protected regions matched well with the hydrophobic cores suggested from the
      crystal structure, and that the NADP(+)-binding domain can be divided into two
      subdomains. The global stability of FNR obtained by H/D exchange with NMR was
      higher than that by chemical denaturation, indicating that H/D exchange is
      especially useful for analyzing the residue-based conformational stability of
      large proteins, for which global unfolding is mostly irreversible. Interestingly,
      more dynamic conformation of the C-terminal subdomain of the NADP(+)-binding
      domain at pD(r) 8.0, the daytime pH in chloroplasts, than at pD(r) 6.0 is likely
      to be involved in the increased binding of NADP(+) for elevating the activity of
      FNR. In light of photosynthesis, the present study provides the first structure
      based relationship of dynamics with function for the FNR-type family in solution.

PMID- 17192258
TI  - The alliance for cellular signaling plasmid collection: a flexible resource for
      protein localization studies and signaling pathway analysis.
AB  - Cellular responses to inputs that vary both temporally and spatially are
      determined by complex relationships between the components of cell signaling
      networks. Analysis of these relationships requires access to a wide range of
      experimental reagents and techniques, including the ability to express the
      protein components of the model cells in a variety of contexts. As part of the
      Alliance for Cellular Signaling, we developed a robust method for cloning large
      numbers of signaling ORFs into Gateway entry vectors, and we created a wide range
      of compatible expression platforms for proteomics applications. To date, we have
      generated over 3000 plasmids that are available to the scientific community via
      the American Type Culture Collection. We have established a website at
      www.signaling-gateway.org/data/plasmid/ that allows users to browse, search, and
      blast Alliance for Cellular Signaling plasmids. The collection primarily contains
      murine signaling ORFs with an emphasis on kinases and G protein signaling genes.
      Here we describe the cloning, databasing, and application of this proteomics
      resource for large scale subcellular localization screens in mammalian cell
      lines.

PMID- 17192260
TI  - Cumulus oophorus-associated glycodelin-C displaces sperm-bound glycodelin-A and 
      F and stimulates spermatozoa-zona pellucida binding.
AB  - Spermatozoa have to swim through the oviduct and the cumulus oophorus before
      fertilization in vivo. In the oviduct, spermatozoa are exposed to glycodelin-A
      and -F that inhibit spermatozoa-zona pellucida binding. In this study, we
      determined whether these glycodelins would inhibit fertilization. The data showed
      that the spermatozoa without previous exposure to glycodelin-A and -F acquired
      glycodelin immunoreactivity during their passage through the cumulus oophorus. On
      the other hand, when glycodelin-A or -F-pretreated spermatozoa were exposed to
      the cumulus oophorus, the zona pellucida binding inhibitory activity of
      glycodelin-A and -F was not only removed, but the spermatozoa acquired enhanced
      zona pellucida binding ability. These actions of the cumulus oophorus were due to
      the presence of a cumulus isoform of glycodelin, designated as glycodelin-C. The
      cumulus cells could convert exogenous glycodelin-A and -F to glycodelin-C, which
      was then released into the surrounding medium. The protein core of glycodelin-C
      was identical to that in other glycodelin isoforms, as demonstrated by mass
      spectrum, peptide mapping, and affinity to anti-glycodelin antibody recognizing
      the protein core of glycodelin. In addition to having a smaller size and a higher
      isoelectric point, glycodelin-C also had lectin binding properties different from
      other isoforms. Glycodelin-C stimulated spermatozoazona pellucida binding in a
      dose-dependent manner, and it effectively displaced sperm-bound glycodelin-A and 
      F. In conclusion, the cumulus cells transform glycodelin-A and -F to glycodelin
      C, which in turn removes the spermatozoazona binding inhibitory glycodelin
      isoforms and enhances the zona binding capacity of spermatozoa passing through
      the cumulus oophorus.

PMID- 17192262
TI  - Structure of Atg5.Atg16, a complex essential for autophagy.
AB  - Atg5 is covalently modified with a ubiquitin-like modifier, Atg12, and the Atg12
      Atg5 conjugate further forms a complex with the multimeric protein Atg16. The
      Atg12-Atg5.Atg16 multimeric complex plays an essential role in autophagy, the
      bulk degradation system conserved in all eukaryotes. We have reported here the
      crystal structure of Atg5 complexed with the N-terminal region of Atg16 at 1.97A
      resolution. Atg5 comprises two ubiquitin-like domains that flank a helix-rich
      domain. The N-terminal region of Atg16 has a helical structure and is bound to
      the groove formed by these three domains. In vitro analysis showed that Arg-35
      and Phe-46 of Atg16 are crucial for the interaction. Atg16, with a mutation at
      these residues, failed to localize to the pre-autophagosomal structure and could
      not restore autophagy in Atg16-deficient yeast strains. Furthermore, these Atg16
      mutants could not restore a severe reduction in the formation of the Atg8
      phosphatidylethanolamine conjugate, another essential factor for autophagy, in
      Atg16-deficient strains under starvation conditions. These results taken together
      suggest that the direct interaction between Atg5 and Atg16 is crucial to the
      performance of their roles in autophagy.

PMID- 17192261
TI  - Crystal structure of the Tp34 (TP0971) lipoprotein of treponema pallidum:
      implications of its metal-bound state and affinity for human lactoferrin.
AB  - The Tp34 (TP0971) membrane lipoprotein of Treponema pallidum, an obligate human
      pathogen and the agent of syphilis, was previously reported to have lactoferrin
      binding properties. Given the non-cultivatable nature of T. pallidum, a structure
      to-function approach was pursued to clarify further potential relationships
      between the Tp34 structural and biochemical properties and its propensity to bind
      human lactoferrin. The crystal structure of a nonacylated, recombinant form of
      Tp34 (rTp34), solved to a resolution of 1.9A(,) revealed two metaloccupied
      binding sites within a dimer; the identity of the ion most likely was zinc.
      Residues from both of the monomers contributed to the interfacial metal-binding
      sites; a novel feature was that the delta-sulfur of methionine coordinated the
      zinc ion. Analytical ultracentrifugation showed that, in solution, rTp34 formed a
      metal-stabilized dimer and that rTp34 bound human lactoferrin with a
      stoichiometry of 2:1. Isothermal titration calorimetry further revealed that
      rTp34 bound human lactoferrin at high (submicromolar) affinity. Finally, membrane
      topology studies revealed that native Tp34 is not located on the outer surface
      (outer membrane) of T. pallidum but, rather, is periplasmic. How propensity of
      Tp34 to bind zinc and the iron-sequestering lactoferrin may relate overall to the
      biology of T. pallidum infection in humans is discussed.

PMID- 17192263
TI  - NMR structural characterization of a minimal peptide antagonist bound to the
      extracellular domain of the corticotropin-releasing factor1 receptor.
AB  - Natural peptide agonists of corticotrophin-releasing factor (CRF) receptors bind
      to the receptor by a two-site mechanism as follows: the carboxyl end of the
      ligand binds the N-terminal extracellular domain (ECD) of the receptor and the
      amino portion of the ligand binds the extracellular face of the seven
      transmembrane region. Recently, peptide antagonists homologous to the 12 C
      terminal residues of CRF have been derived, which bind the CRF(1) receptor
      through an interaction with the ECD. Here we characterized the binding of a
      minimal 12-residue peptide antagonist while bound to the isolated ECD of the
      CRF(1) receptor. We have expressed and purified soluble and properly folded ECD
      independent from the seven-transmembrane region as a thioredoxin fusion protein
      in Escherichia coli. A model of the peptide antagonist, cyclic corticotrophin
      releasing factor residues 30-41 (cCRF(30-41)), was calculated while bound to the
      recombinant ECD using transferred nuclear Overhauser effect spectroscopy.
      Although the peptide is unstructured in solution, it adopts an alpha-helical
      conformation when bound to the ECD. Residues of cCRF(30-41) comprising the
      binding interface with the ECD were mapped using saturation transfer difference
      NMR. Two hydrophobic residues (Met(38) and Ile(41)) as well as two amide groups
      (Asn(34) and the C-terminal amide) on one face of the helix defined the binding
      epitope of the antagonist. This epitope may be used as a starting point for
      development of non-peptide antagonists targeting the ECD of this receptor.

PMID- 17192264
TI  - Structural diversity of the hagfish variable lymphocyte receptors.
AB  - Variable lymphocyte receptors (VLRs) are recently discovered leucine-rich repeat
      (LRR) family proteins that mediate adaptive immune responses in jawless fish.
      Phylogenetically it is the oldest adaptive immune receptor and the first one with
      a non-immunoglobulin fold. We present the crystal structures of one VLR-A and two
      VLR-B clones from the inshore hagfish. The hagfish VLRs have the characteristic
      horseshoe-shaped structure of LRR family proteins. The backbone structures of
      their LRR modules are highly homologous, and the sequence variation is
      concentrated on the concave surface of the protein. The conservation of key
      residues suggests that our structures are likely to represent the LRR structures
      of the entire repertoire of jawless fish VLRs. The analysis of sequence
      variability, prediction of protein interaction surfaces, amino acid composition
      analysis, and structural comparison with other LRR proteins suggest that the
      hypervariable concave surface is the most probable antigen binding site of the
      VLR.

PMID- 17192265
TI  - Structural and functional insights into intramolecular fructosyl transfer by
      inulin fructotransferase.
AB  - Inulin fructotransferase (IFTase), a member of glycoside hydrolase family 91,
      catalyzes depolymerization of beta-2,1-fructans inulin by successively removing
      the terminal difructosaccharide units as cyclic anhydrides via intramolecular
      fructosyl transfer. The crystal structures of IFTase and its substrate-bound
      complex reveal that IFTase is a trimeric enzyme, and each monomer folds into a
      right-handed parallel beta-helix. Despite variation in the number and
      conformation of its beta-strands, the IFTase beta-helix has a structure that is
      largely reminiscent of other beta-helix structures but is unprecedented in that
      trimerization is a prerequisite for catalytic activity, and the active site is
      located at the monomer-monomer interface. Results from crystallographic studies
      and site-directed mutagenesis provide a structural basis for the exolytic-type
      activity of IFTase and a functional resemblance to inverting-type
      glycosyltransferases.

PMID- 17192267
TI  - Enhancer of polycomb1, a novel homeodomain only protein-binding partner, induces
      skeletal muscle differentiation.
AB  - Homeodomain only protein, Hop, is an unusual small protein that modulates target
      gene transcription without direct binding to DNA. Here we show that Hop interacts
      with Enhancer of Polycomb1 (Epc1), a homolog of a Drosophila polycomb group gene
      product that regulates transcription, to induce the skeletal muscle
      differentiation. Yeast two-hybrid assay with the human adult heart cDNA library
      revealed that Hop can associate with Epc1. The amino-terminal domain of Epc1 as
      well as full Epc1 physically interacted with Hop in mammalian cells and in yeast.
      Epc1 is highly expressed in the embryonic heart and adult skeletal muscles. Serum
      deprivation induced differentiation of H9c2, a myoblast cell line, into skeletal
      myocytes, and Epc1 was up-regulated. Differentiation of H9c2 was induced by Epc1
      overexpression, although it was severely impaired in Epc1-knockdown cells. Co
      transfection of Hop potentiated Epc1-induced transactivation of myogenin and
      myotube formation. Hop knock-out mice elicited a decrease in myosin heavy chain
      and myogenin expressions in skeletal muscle and showed delay in hamstring muscle
      healing after injury. Differentiation was impaired in skeletal myoblasts from Hop
      knock-out mice. These results suggest that Epc1 plays a role in the initiation of
      skeletal muscle differentiation, and its interaction with Hop is required for the
      full activity.

PMID- 17192266
TI  - A conserved pathway that controls c-Myc protein stability through opposing
      phosphorylation events occurs in yeast.
AB  - The c-Myc transcription factor is a key regulator of cell proliferation and cell
      fate decisions. c-Myc overexpression is observed in a variety of human tumors,
      revealing the importance of maintaining normal levels of c-Myc protein. c-Myc
      protein stability in mammalian cells is controlled by interdependent and
      sequential phosphorylation and dephosphorylation events on two highly conserved
      residues, serine 62 and threonine 58. Here we show that these sequential
      phosphorylation and dephosphorylation events and their effect on c-Myc stability
      also occurs in the model system Saccharomyces cerevisiae. These results suggest
      the presence of a conserved pathway in yeast that controls protein turnover in
      response to a specific phospho-degron sequence. These findings have implications
      regarding conserved pathways for regulated protein degradation, and they validate
      the use of genetically tractable yeast for the study of the turnover of proteins
      such as c-Myc that contain this motif.

PMID- 17192268
TI  - Mutation analysis of the short cytoplasmic domain of the cell-cell adhesion
      molecule CEACAM1 identifies residues that orchestrate actin binding and lumen
      formation.
AB  - CEACAM1-4S (carcinoembryonic antigen cell adhesion molecule 1, with 4 ectodomains
      and a short, 12-14 amino acid cytoplasmic domain) mediates lumen formation via an
      apoptotic and cytoskeletal reorganization mechanism when mammary epithelial cells
      are grown in a three-dimensional model of mammary morphogenesis. We show by
      quantitative yeast two-hybrid, BIAcore, NMR HSQC and STD, and confocal analyses
      that amino acids phenylalanine (Phe(454)) and lysine (Lys(456)) are key residues
      that interact with actin orchestrating the cytoskeletal reorganization. A CEACAM1
      membrane model based on vitamin D-binding protein that predicts an interaction of
      Phe(454) at subdomain 3 of actin was supported by inhibition of binding of actin
      to vitamin D-binding protein by the cytoplasmic domain peptide. We also show that
      residues Thr(457) and/or Ser(459) are phosphorylated in CEACAM1-transfected cells
      grown in three-dimensional culture and that mutation analysis of these residues
      (T457A/S459A) or F454A blocks lumen formation. These studies demonstrate that a
      short cytoplasmic domain membrane receptor can directly mediate substantial
      intracellular signaling.

PMID- 17192269
TI  - Dissecting the N-terminal myosin binding site of human cardiac myosin-binding
      protein C. Structure and myosin binding of domain C2.
AB  - Myosin-binding protein C (MyBP-C) binds to myosin with two binding sites, one
      close to the N terminus and the other at the C terminus. Here we present the
      solution structure of one part of the N-terminal binding site, the third
      immunoglobulin domain of the cardiac isoform of human MyBP-C (cC2) together with
      a model of its interaction with myosin. Domain cC2 has the beta-sandwich
      structure expected from a member of the immunoglobulin fold. The C-terminal part
      of the structure of cC2 is very closely related to telokin, the myosin binding
      fragment of myosin light chain kinase. Domain cC2 also contains two cysteines on
      neighboring strands F and G, which would be able to form a disulfide bridge in a
      similar position as in telokin. Using NMR spectroscopy and isothermal titration
      calorimetry we demonstrate that cC2 alone binds to a fragment of myosin, S2Delta,
      with low affinity (kD = 1.1 mM) but exhibits a highly specific binding site. This
      consists of the C-terminal surface of the C'CFGA' beta-sheet, which includes
      Glu(301), a residue mutated to Gln in the disease familial hypertrophic
      cardiomyopathy. The binding site on S2 was identified by a combination of NMR
      binding experiments of cC2 with S2Delta containing the cardiomyopathy-linked
      mutation R870H and molecular modeling. This mutation lowers the binding affinity
      and changes the arrangement of side chains at the interface. Our model of the cC2
      S2Delta complex gives a first glimpse of details of the MyBP-C-myosin
      interaction. Using this model we suggest that most key interactions are between
      polar amino acids, explaining why the mutations E301Q in cC2 and R870H in S2Delta
      could be involved in cardiomyopathy. We expect that this model will stimulate
      future research to further refine the details of this interaction and their
      importance for cardiomyopathy.

PMID- 17192270
TI  - Fine mapping of an epitope recognized by an invasion-inhibitory monoclonal
      antibody on the malaria vaccine candidate apical membrane antigen 1.
AB  - Antibodies that inhibit red blood cell invasion by the Plasmodium merozoite block
      the erythrocytic cycle responsible for clinical malaria. The invasion-inhibitory
      monoclonal antibody (mAb) 4G2 recognizes a conserved epitope in the ectodomain of
      the essential Plasmodium falciparum microneme protein and vaccine candidate,
      apical membrane antigen 1 (PfAMA1). Here we demonstrate that purified Fab
      fragments of 4G2 inhibit invasion markedly more efficiently than the intact mAb,
      suggesting that the invasion-inhibitory activity of this mAb is not due solely to
      steric effects and that the epitope lies within a functionally critical region of
      the molecule. We have taken advantage of a synthetic gene encoding a modified
      form of PfAMA1, and existing x-ray crystal structure data, to fully characterize
      this epitope. We first validate the gene by demonstrating that it fully
      complements the function of the authentic gene in P. falciparum. We then use it
      to identify a group of residues within the previously described domain II loop of
      PfAMA1 that are critical for recognition by mAb 4G2 and demonstrate that the
      epitope lies exclusively within this loop with no contributions from residues in
      other domains of the molecule. This is the first complete characterization of a
      conserved invasion-inhibitory epitope on PfAMA1. Our results will aid in the
      design of subunit vaccines designed to generate a broadly effective, focused anti
      PfAMA1 protective immune response and may help elucidate the function of PfAMA1.

PMID- 17192272
TI  - The dynamic envelope of a fusion class II virus. Prefusion stages of semliki
      forest virus revealed by electron cryomicroscopy.
AB  - Semliki Forest virus is among the prototypes for Class II virus fusion and
      targets the endosomal membrane. Fusion protein E1 and its envelope companion E2
      are both anchored in the viral membrane and form an external shell with
      protruding spikes. In acid environments, mimicking the early endosomal milieu,
      surface epitopes in the virus rearrange along with exposure of the fusion loop.
      To visualize this transformation into a fusogenic stage, we determined the
      structure of the virus at gradually lower pH values. The results show that while
      the fusion loop is available for external interaction and the shell and stalk
      domains of the spike begin to deteriorate, the E1 and E2 remain in close contact
      in the spike head. This unexpected observation points to E1 and E2 cooperation
      beyond the fusion loop exposure stage and implies a more prominent role for E2 in
      guiding membrane close encounter than has been earlier anticipated.

PMID- 17192271
TI  - Med19(Rox3) regulates Intermodule interactions in the Saccharomyces cerevisiae
      mediator complex.
AB  - The Saccharomyces cerevisiae Mediator is a 25-subunit complex that facilitates
      both transcriptional activation and repression. Structural and functional studies
      have divided Mediator subunits into four distinct modules. The Head, Middle, and
      Tail modules form the core functional Mediator complex, whereas a fourth, the Cyc
      C module, is variably associated with the core. By purifying Mediator from a
      strain lacking the Med19(Rox3) subunit, we have found that a complex missing only
      the Med19(Rox3) subunit can be isolated under mild conditions. Additionally, we
      have established that the entire Middle module is released when the
      Deltamed19(rox3) Mediator is purified under more stringent conditions. In
      contrast to most models of the modular structure of Mediator, we show that
      release of the Middle module in the Deltamed19(rox3) Mediator leaves a stable
      complex made up solely of Head and Tail subunits. Both the intact and Head-Tail
      Deltamed19(rox3) Mediator complexes have defects in enhanced basal transcription,
      enhanced TFIIH phosphorylation of the CTD, as well as binding of RNA Pol II and
      the CTD. The largely intact Deltamed19(rox3) complex facilitates activated
      transcription at levels similar to the wild type Mediator. In the absence of the
      Middle module, however, the Deltamed19(rox3) Mediator is unable to facilitate
      activated transcription. Although the Middle module is unnecessary for holding
      the Head and Tail modules together, it is required for the complex to function as
      a conduit between activators and the core transcription machinery.

PMID- 17192273
TI  - Transcriptional regulation of FasL expression and participation of sTNF-alpha in
      response to sertoli cell injury.
AB  - The Fas/FasL signaling pathway has previously been demonstrated to be critical
      for triggering germ cell apoptosis in response to mono-(2-ethylhexyl)phthalate
      (MEHP)-induced Sertoli cell injury. Although Sertoli cells ubiquitously express
      the FasL protein, MEHP-induced germ cell apoptosis appears to tightly correlate
      with increased levels of Sertoli cell FasL. Here we characterize the
      transcriptional regulation of the murine FasL gene in Sertoli cells after MEHP
      exposure. A serial deletion strategy for 1.5 kb of the 5'-upstream activating
      sequence of the FasL promoter was used to determine transcriptional activity in
      response to MEHP. Luciferase activity of the FasL promoter in the rat Sertoli
      cell line ASC-17D revealed that two regions, -500 to -324 and -1250 to -1000,
      were necessary to drive the inducible transcription of FasL. Sequence analysis of
      these two regions revealed two cis-regulatory elements, NF-kappaB and Sp-1. By
      site-directed mutagenesis, electrophoretic mobility shift and chromatin
      immunoprecipitation assays, it was confirmed that MEHP-induced FasL expression is
      enhanced through the transcriptional regulation of both NF-kappaB and Sp-1.
      Experiments performed both in vitro and in vivo revealed that MEHP exposure
      results in an increased production of sTNF-alpha and that sTNF-alpha-mediated NF
      kappaB activation causes robust increases in FasL levels in both the ASC-17D
      Sertoli cell line and in primary rat Sertoli cell/germ cell co-cultures. In the
      seminiferous epithelium, Sertoli cells express TNFR1, whereas germ cells produce
      TNF-alpha. Therefore, sTNF-alpha released by germ cells after MEHP-induced
      Sertoli cell injury acts upon Sertoli cell TNFR1 and activates NF-kappaB and Sp-1
      that consequently causes a robust induction of FasL expression. These novel
      findings point to a potential "feed-forward" signaling mechanism by which germ
      cells prompt Sertoli cells to trigger their apoptotic elimination.

PMID- 17192274
TI  - PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading
      to Src activation.
AB  - Phosphatase of regenerating liver 3 (PRL3) is overexpressed in a variety of
      tumors, and high levels of PRL3 expression are associated with tumorigenesis and
      metastasis. Consistent with an oncogenic role for PRL3, we show that ectopic PRL3
      expression promotes cell proliferation and invasion. However, little is known
      about the molecular basis for PRL3 function. Obtaining this knowledge is vital
      for understanding PRL3-mediated disease processes and for the development of
      novel anticancer therapies targeted to PRL3. Here we report that up-regulation of
      PRL3 activates the Src kinase, which initiates a number of signal pathways
      culminating in the phosphorylation of ERK1/2, STAT3, and p130(Cas). The
      activation of these pathways likely contributes to the increased cell growth and
      motility of PRL3 cells. We provide evidence that PRL3 induces Src activation
      through down-regulation of Csk, a negative regulator of Src. Importantly, Src
      activation and Csk down-regulation are also observed in colon cancer cells
      expressing a higher level of PRL3. Thus, we have revealed a biochemical mechanism
      for the PRL3-mediated cell invasion and proliferation in which elevated PRL3
      expression causes a reduction in Csk level, leading to Src activation.

PMID- 17192275
TI  - Colonic anion secretory defects and metabolic acidosis in mice lacking the NBC1
      Na+/HCO3- cotransporter.
AB  - The NBC1 Na+/HCO3- cotransporter is expressed in many tissues, including kidney
      and intestinal epithelia. NBC1 mutations cause proximal renal tubular acidosis in
      humans, consistent with its role in HCO3- absorption in the kidney. In intestinal
      and colonic epithelia, NBC1 localizes to basolateral membranes and is thought to
      function in anion secretion. To test the hypothesis that NBC1 plays a role in
      transepithelial HCO3- secretion in the intestinal tract, null mutant (NBC1-/-)
      mice were prepared by targeted disruption of its gene (Slc4a4). NBC1-/- mice
      exhibited severe metabolic acidosis, growth retardation, reduced plasma Na+,
      hyperal-dosteronism, splenomegaly, abnormal dentition, intestinal obstructions,
      and death before weaning. Intracellular pH (pH(i)) was not altered in cAMP
      stimulated epithelial cells of NBC1-/- cecum, but pH(i) regulation during sodium
      removal and readdition was impaired. Bioelectric measurements of NBC1-/- colons
      revealed increased amiloride-sensitive Na+ absorption. In Ringer solution
      containing both Cl- and HCO3-, the magnitude of cAMP-stimulated anion secretion
      was normal in NBC1-/- distal colon but increased in proximal colon, with the
      increase largely supported by enhanced activity of the basolateral NKCC1 Na+-K+
      2Cl- cotransporter. Anion substitution studies in which carbonic anhydrase was
      inhibited and transepithelial anion conductance was limited to HCO3- revealed a
      sharp decrease in both cAMP-stimulated HCO3- secretion and SITS-sensitive current
      in NBC1-/- proximal colon. These results are consistent with the known function
      of NBC1 in HCO3- absorption in the kidney and demonstrate that NBC1 activity is a
      component of the basolateral mechanisms for HCO3- uptake during cAMP-stimulated
      anion secretion in the proximal colon.

PMID- 17192276
TI  - Regulation of NF-kappaB-dependent gene expression by the POU domain transcription
      factor Oct-1.
AB  - Maintenance of the cells of the vessel wall in a quiescent state is an important
      aspect of normal vascular physiology. Transcriptional repressors are widely
      believed to regulate this process, yet the exact factors involved and the
      mechanism of repression are not known. Here, we report that the POU domain
      transcription factor Oct-1 represses the expression of E-selectin and vascular
      cell adhesion molecule (VCAM-1), two cytokine-inducible, NF-kappaB-dependent
      endothelial-leukocyte adhesion molecules that participate in the leukocyte
      recruitment phase of the inflammatory response. Co-transfection and
      microinjection studies demonstrate that Oct-1 blocks tumor necrosis factor alpha
      stimulated E-selectin and VCAM-1 expression. Gene expression arrays indicate that
      control of tumor necrosis factor alpha-induced, NF-kappaB-dependent gene
      expression by Oct-1 is promoter-specific. A DNA-binding mutant of Oct-1 represses
      NF-kappaB-dependent reporter gene expression. Biochemically, Oct-1 interacts with
      p65, suggesting that Oct-1 is involved in the regulation of NF-kappaB
      transactivation function. NF-kappaB-dependent gene expression is more pronounced
      in Oct-1-deficient than in wild-type murine embryonic fibroblasts, and
      reintroduction of human Oct-1 abolishes these differences. Finally, the cytokine
      interleukin-6 induces Oct-1 gene expression, providing a biologically relevant
      means by which NF-kappaB-dependent gene expression can be selectively reverted by
      Oct-1 to quiescent levels.

PMID- 17192277
TI  - Retained central venous haemodialysis access catheters.

PMID- 17192278
TI  - Doppler sonography in renal artery stenosis--does the Resistive Index predict the
      success of intervention?

PMID- 17192279
TI  - Enhancement of epithelial sodium channel expression in renal cortical collecting
      ducts cells by advanced glycation end products.
AB  - BACKGROUND: The epithelial sodium channel (ENaC) is a complex, and the alphaENaC
      subunit has a crucial role in sodium uptake induced by aldosterone in the distal
      nephron. Although experimental animal models of diabetes have demonstrated up
      regulation of alphaENaC expression in renal cortical collecting duct (CCD) cells,
      the molecular mechanism remains unclear. Advanced glycation end products (AGEs)
      are by-products of long-term hyperglycaemia and comprise a significant pathogenic
      factor in diabetic nephropathy. We hypothesize that AGEs play a role in
      regulating alphaENaC gene expression. METHODS: Mouse CCD cells (mpkCCDcl(4)) were
      cultured with AGE to determine the effects of AGE on alphaENaC expression and
      sodium uptake. Gene expressions of ENaC were measured by real-time PCR and sodium
      uptake was measured with fluorescent dye as a sodium indicator (SBFI-AM). This
      study analysed mitogen-activated protein kinases signalling pathways by western
      blotting. Cells co-transfected with plasmids of the alphaENaC promoter carrying a
      luciferase reporter and plasmids expressing wild-type or mutant serum- and
      glucocorticoid-induced kinase 1 (Sgk1) mRNA were stimulated with AGE to identify
      the signalling pathway. RESULTS: The AGEs, stimulated in a time- and dose
      dependent manner, enhanced alphaENaC mRNA expression and sodium uptake in
      mpkCCDcl(4) cells. The AGEs also significantly stimulated Sgk1 mRNA and Sgk1
      activity in a time- and dose-dependent manner. Co-transfected with plasmid
      expressing mutant Sgk1 significantly limited stimulated alphaENaC promoter-driven
      luciferase activity by AGEs in mpkCCDcl(4) cells. CONCLUSION: Experimental
      results indicate that AGEs induced alphaENaC expression and increased sodium
      uptake in renal CCD cells. The mechanism through which AGEs activate alphaENaC
      expression may be via activation of Sgk1 in mpkCCDcl(4) cells.

PMID- 17192280
TI  - Thyroid hormone inhibits biliary growth in bile duct-ligated rats by
      PLC/IP(3)/Ca(2+)-dependent downregulation of SRC/ERK1/2.
AB  - The role of the thyroid hormone agonist 3,3',5 l-tri-iodothyronine (T3) on
      cholangiocytes is unknown. We evaluated the in vivo and in vitro effects of T3 on
      cholangiocyte proliferation of bile duct-ligated (BDL) rats. We assessed the
      expression of alpha(1)-, alpha(2)-, beta(1)-, and beta(2)-thyroid hormone
      receptors (THRs) by immunohistochemistry in liver sections from normal and BDL
      rats. BDL rats were treated with T3 (38.4 mug/day) or vehicle for 1 wk. We
      evaluated 1) biliary mass and apoptosis in liver sections and 2) proliferation in
      cholangiocytes. Serum-free T3 levels were measured by chemiluminescence. Purified
      BDL cholangiocytes were treated with 0.2% BSA or T3 (1 muM) in the
      absence/presence of U-73122 (PLC inhibitor) or BAPTA/AM (intracellular Ca(2+)
      chelator) before measurement of PCNA protein expression by immunoblots. The in
      vitro effects of T3 (1 muM) on 1) cAMP, IP(3), and Ca(2+) levels and 2) the
      phosphorylation of Src Tyr139 and Tyr530 (that, together, regulate Src activity)
      and ERK1/2 of BDL cholangiocytes were also evaluated. alpha(1)-, alpha(2)-,
      beta(1)-, and beta(2)-THRs were expressed by bile ducts of normal and BDL rats.
      In vivo, T3 decreased cholangiocyte proliferation of BDL rats. In vitro, T3
      inhibition of PCNA protein expression was blocked by U-73122 and BAPTA/AM.
      Furthermore, T3 1) increased IP(3) and Ca(2+) levels and 2) decreased Src and
      ERK1/2 phosphorylation of BDL cholangiocytes. T3 inhibits cholangiocyte
      proliferation of BDL rats by PLC/IP(3)/Ca(2+)-dependent decreased phosphorylation
      of Src/ERK1/2. Activation of the intracellular signals triggered by T3 may
      modulate the excess of cholangiocyte proliferation in liver diseases.

PMID- 17192282
TI  - Intracellular cAMP: the "switch" that triggers on "spontaneous transient outward
      currents" generation in freshly isolated myocytes from thoracic aorta.
AB  - Spontaneous transient outward currents (STOCs) have been reported in resistance
      and small arteries but have not yet been found in thoracic aorta. Do thoracic
      aorta myocytes possess cellular machinery that generates STOCs? It was found that
      the majority of aortic myocytes do not generate STOCs. STOCs were generated in
      8.7% of freshly isolated aortic myocytes. Myocytes that did not generate STOCs we
      have called "silent" myocytes and myocytes with STOCs have been called "active."
      STOCs recorded in active myocytes were voltage dependent and were inhibited by
      ryanodine, caffeine, and charybdotoxin. Forskolin was reported to increase STOCs
      frequency in myocytes isolated from resistance arteries. Forskolin (10 microM)
      triggered STOCs generation in 35.1% of silent aortic myocytes. In 36.8% percent
      of silent myocytes, forskolin did not trigger STOCs but increased the amplitude
      of charybdotoxin-sensitive outward net current to 136.1 +/- 8.5% at 0 mV.
      Membrane-permeable 8BrcAMP triggered STOCs generation in 38.7% of silent
      myocytes. Forskolin- or 8BrcAMP-triggered STOCs were inhibited by charybdotoxin.
      8BrcAMP also increased open probability of BK(Ca) channels in BAPTA-AM-pretreated
      cells. Our data demonstrate that, in contrast to resistance arteries, STOCs are
      present just in the minority of myocytes in the thoracic aorta. However, cellular
      machinery that generates STOCs can be "switched" on by cAMP. Such an inactive
      cellular mechanism could modulate the contractility of the thoracic aorta in
      response to physiological demand.

PMID- 17192281
TI  - Hypertonicity triggers RhoA-dependent assembly of myosin-containing striated
      polygonal actin networks in endothelial cells.
AB  - Endothelial cells respond to mechanical stresses of the circulation with
      cytoskeletal rearrangements such as F-actin stress fiber alignment along the axis
      of fluid flow. Endothelial cells are exposed to hypertonic stress in the renal
      medulla or during mannitol treatment of cerebral edema. We report here that
      arterial endothelial cells exposed to hypertonic stress rearranged F-actin into
      novel actin-myosin II fibers with regular 0.5-microm striations, in which alpha
      actinin colocalizes with actin. These striated fibers assembled over hours into
      three-dimensional, irregular, polygonal actin networks most prominent at the cell
      base, and occasionally surrounding the nucleus in a geodesic-like structure.
      Hypertonicity-induced assembly of striated polygonal actin networks was inhibited
      by cytochalasin D, blebbistatin, cell ATP depletion, and intracellular Ca(2+)
      chelation but did not require intact microtubules, regulatory volume increase, or
      de novo RNA or protein synthesis. Striated polygonal actin network assembly was
      insensitive to inhibitors of MAP kinases, tyrosine kinases, or
      phosphatidylinositol 3-kinase, but was prevented by C3 exotoxin, by the RhoA
      kinase inhibitor Y-27632, and by overexpressed dominant-negative RhoA. In
      contrast, overexpression of dominant-negative Rac or of dominant-negative cdc42
      cDNAs did not prevent striated polygonal actin network assembly. The actin
      networks described here are novel in structure, as striated actin-myosin
      structures in nonmuscle cells, as a cellular response to hypertonicity, and as a
      cytoskeletal regulatory function of RhoA. Endothelial cells may use RhoA
      dependent striated polygonal actin networks, possibly in concert with
      cytoskeletal load-bearing elements, as a contractile, tension-generating
      component of their defense against isotropic compressive forces.

PMID- 17192283
TI  - Identification of a novel interaction between the Ca(2+)-binding protein S100A11
      and the Ca(2+)- and phospholipid-binding protein annexin A6.
AB  - S100A11 is a member of the S100 family of EF-hand Ca(2+)-binding proteins, which
      is expressed in smooth muscle and other tissues. Ca(2+) binding to S100A11
      induces a conformational change that exposes a hydrophobic surface for
      interaction with target proteins. Affinity chromatography with immobilized
      S100A11 was used to isolate a 70-kDa protein from smooth muscle that bound to
      S100A11 in a Ca(2+)-dependent manner and was identified by mass spectrometry as
      annexin A6. Direct Ca(2+)-dependent interaction between S100A11 and annexin A6
      was confirmed by affinity chromatography of the purified bacterially expressed
      proteins, by gel overlay of annexin A6 with purified S100A11, by chemical cross
      linking, and by coprecipitation of S100A11 with annexin A6 bound to liposomes.
      The expression of S100A11 and annexin A6 in the same cell type was verified by RT
      PCR and immunocytochemistry of isolated vascular smooth muscle cells. The site of
      binding of S100A11 on annexin A6 was investigated by partial tryptic digestion
      and deletion mutagenesis. The unique NH(2) terminal head region of annexin A6 was
      not required for S100A11 binding, but binding sites were identified in both NH(2)
      and COOH-terminal halves of the molecule. We hypothesize that an agonist-induced
      increase in cytosolic free [Ca(2+)] leads to formation of a complex of S100A11
      and annexin A6, which forms a physical connection between the plasma membrane and
      the cytoskeleton, or plays a role in the formation of signaling complexes at the
      level of the sarcolemma.

PMID- 17192284
TI  - Class A scavenger receptor-mediated cell adhesion requires the sequential
      activation of Lyn and PI3-kinase.
AB  - Class A scavenger receptors (SR-A) participate in multiple macrophage functions
      including macrophage adhesion to modified proteins. SR-A-mediated adhesion may
      therefore contribute to chronic inflammation by promoting macrophage accumulation
      at sites of protein modification. The mechanisms that couple SR-A binding to
      modified proteins with increased cell adhesion have not been defined. In this
      study, SR-A expressing HEK cells and SR-A+/+ or SR-A-/- macrophages were used to
      delineate the signaling pathways required for SR-A-mediated adhesion to modified
      protein. Inhibiting G(i/o) activation, which decreases initial SR-A-mediated cell
      attachment, did not prevent the subsequent spreading of attached cells. In
      contrast, inhibition of Src kinases or PI3-kinase abolished SR-A-dependent cell
      spreading without affecting SR-A-mediated cell attachment. Consistent with these
      results, the Src kinase Lyn and PI3-kinase were sequentially activated during SR
      A-mediated cell spreading. Furthermore, activation of both Lyn and PI3-kinase was
      required for enhancing paxillin phosphorylation. Activation of a Src kinase-PI3
      kinase-Akt pathway was also observed in cells expressing a truncated SR-A protein
      that does not internalize indicating that SR-A-mediated activation of
      intracellular signaling cascades following adhesion to MDA-BSA is independent of
      receptor internalization. Thus SR-A binding to modified protein activates
      signaling cascades that have distinct roles in regulating initial cell attachment
      and subsequent cell spreading.

PMID- 17192285
TI  - Upregulation of Na+/Ca2+ exchanger contributes to the enhanced Ca2+ entry in
      pulmonary artery smooth muscle cells from patients with idiopathic pulmonary
      arterial hypertension.
AB  - A rise in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary artery
      smooth muscle cells (PASMC) is a trigger for pulmonary vasoconstriction and a
      stimulus for PASMC proliferation and migration. Multiple mechanisms are involved
      in regulating [Ca(2+)](cyt) in human PASMC. The resting [Ca(2+)](cyt) and Ca(2+)
      entry are both increased in PASMC from patients with idiopathic pulmonary
      arterial hypertension (IPAH), which is believed to be a critical mechanism for
      sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling
      in these patients. Here we report that protein expression of NCX1, an NCX family
      member of Na(+)/Ca(2+) exchanger proteins is upregulated in PASMC from IPAH
      patients compared with PASMC from normal subjects and patients with other
      cardiopulmonary diseases. The Na(+)/Ca(2+) exchanger operates in a forward
      (Ca(2+) exit) and reverse (Ca(2+) entry) mode. By activating the reverse mode of
      Na(+)/Ca(2+) exchange, removal of extracellular Na(+) caused a rapid increase in
      [Ca(2+)](cyt), which was significantly enhanced in IPAH PASMC compared with
      normal PASMC. Furthermore, passive depletion of intracellular Ca(2+) stores using
      cyclopiazonic acid (10 microM) not only caused a rise in [Ca(2+)](cyt) due to
      Ca(2+) influx through store-operated Ca(2+) channels but also mediated a rise in
      [Ca(2+)](cyt) via the reverse mode of Na(+)/Ca(2+) exchange. The upregulated NCX1
      in IPAH PASMC led to an enhanced Ca(2+) entry via the reverse mode of
      Na(+)/Ca(2+) exchange, but did not accelerate Ca(2+) extrusion via the forward
      mode of Na(+)/Ca(2+) exchange. These observations indicate that the upregulated
      NCX1 and enhanced Ca(2+) entry via the reverse mode of Na(+)/Ca(2+) exchange are
      an additional mechanism responsible for the elevated [Ca(2+)](cyt) in PASMC from
      IPAH patients.

PMID- 17192286
TI  - Nitric oxide increases toxicity of hydrogen peroxide against rat liver
      endothelial cells and hepatocytes by inhibition of hydrogen peroxide degradation.
AB  - Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) show cooperativity in their
      cytotoxic action. The present study was performed to decipher the mechanisms
      underlying this phenomenon. In cultured liver endothelial cells and in cultured,
      glutathione-depleted hepatocytes, the combined exposure to NO (released by
      spermine NONOate, 1 mM) and H(2)O(2) (released by glucose oxidase) induced cell
      injury that was far higher than the injury elicited by NO or H(2)O(2) alone. In
      both cell types, the addition of the NO donor increased H(2)O(2) steady-state
      levels, although with different kinetics: in hepatocytes, the increase in
      H(2)O(2) levels was already evident at early time points while in liver
      endothelial cells it became evident after > or =2 h of incubation. NO exposure
      inhibited H(2)O(2) degradation, assessed after addition of 50 microM, 200 microM,
      or 4 mM authentic H(2)O(2), significantly in both cell types. However, again,
      early and delayed inhibition was observed. The late inhibition of H(2)O(2)
      degradation in endothelial cells was paralleled by a decrease in glutathione
      peroxidase activity. Glutathione peroxidase inactivation was prevented by hypoxia
      or by ascorbate, suggesting inactivation by reactive nitrogen oxide species
      (NO(x)). Early inhibition of H(2)O(2) degradation by NO, in contrast, could be
      mimicked by the catalase inhibitor azide. Together, these results suggest that
      the cooperative effect of NO and H(2)O(2) is due to inhibition of H(2)O(2)
      degradation by NO, namely to inhibition of catalase by NO itself (predominant in
      hepatocytes) and/or to inhibition of glutathione peroxidase by NO(x) (prevailing
      in endothelial cells).

PMID- 17192287
TI  - Glycemic thresholds for activation of counterregulatory hormone and symptom
      responses in islet transplant recipients.
AB  - CONTEXT: In patients with type 1 diabetes and reduced awareness of hypoglycemia,
      the glycemic thresholds for activation of counterregulatory hormone and symptom
      responses to hypoglycemia are impaired, in part due to recurrent episodes of
      hypoglycemia. Islet transplantation can ameliorate occurrences of hypoglycemia in
      these patients. OBJECTIVE: The objective of the study was to determine whether
      the avoidance of hypoglycemia achieved through islet transplantation results in
      improved glycemic thresholds for counterregulatory responses. SETTING: The study
      was conducted at a general clinical research center. PARTICIPANTS: Seven islet
      transplant recipients, six type 1 diabetic, and eight nondiabetic control
      subjects participated in the study. INTERVENTION: We performed a stepped
      hyperinsulinemic hypoglycemic clamp and, in 12 subjects, a paired
      hyperinsulinemic euglycemic clamp to calculate the glycemic thresholds for and
      magnitude of counterregulatory responses. RESULTS: The glycemic thresholds for
      all counterregulatory hormone and symptom responses in the islet transplant group
      were comparable with normal and higher than in the type 1 diabetes group (P <
      0.01 for glucagon; P < 0.05 for epinephrine). The magnitude of the glucagon and
      epinephrine responses in the islet transplant group, although greater than in the
      type 1 diabetes group (P < 0.05 for both), remained less than normal (P < 0.01
      for glucagon; P < 0.05 for epinephrine). The magnitude of GH secretion in the
      islet transplant group was comparable with normal and greater than in the type 1
      diabetes group (P < 0.05). CONCLUSIONS: The glycemic thresholds for activation of
      counterregulatory hormone and symptom responses appear normal after islet
      transplantation; however, the magnitudes of the glucagon and epinephrine
      responses remain impaired.

PMID- 17192288
TI  - Endometrial effects of tibolone.
AB  - BACKGROUND AND OBJECTIVES: The Tibolone Histology of the Endometrium and Breast
      Endpoints Study is a multicenter, randomized, double-blind study designed to
      address the conflicting reports in the literature about the endometrial safety of
      tibolone (1.25 or 2.5 mg/d). Tibolone was compared with continuous combined
      conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) (0.625 +
      2.5 mg/d). METHODS: Subjects were randomized in a 1:1:2 ratio to tibolone 1.25
      mg/d, 2.5 mg/d, and CEE/MPA, respectively. The one-sided 95% confidence interval
      (CI) has been evaluated for the incidence of abnormal endometrial histology
      (hyperplasia or carcinoma) and hyperplasia and carcinoma separately for each of
      the two treatment groups and the treatment groups combined after 1 and 2 yr of
      treatment with tibolone, compared with CEE/MPA. RESULTS: A total of 3240 women
      were randomized, with 3224 receiving at least one dose of study medication. The
      incidence and upper one-sided 95% CI for the incidence of abnormal endometrium
      (hyperplasia or carcinoma), and hyperplasia and carcinoma separately, were
      calculated at end point, yr 1, and yr 2. The incidence (upper one-sided 95% CI)
      of abnormal endometrium at end point was 0.0 (0.5), 0.0 (0.4), and 0.2 (0.5) in
      the tibolone 1.25 mg, 2.5 mg, and CEE/MPA groups, respectively. During the entire
      treatment period, amenorrhea was reported more frequently with tibolone 1.25 mg
      (78.7%) and 2.5 mg (71.4%) than CEE/MPA (44.9%). CONCLUSION: The Tibolone
      Histology of the Endometrium and Breast Endpoints Study results confirm previous
      findings that tibolone does not induce endometrial hyperplasia or carcinoma in
      postmenopausal women, and it is associated with a better vaginal bleeding profile
      than CEE/MPA.

PMID- 17192289
TI  - Combining growth hormone releasing hormone-arginine and synacthen testing
      diminishes the cortisol response.
AB  - OBJECTIVES: The GHRH/arginine test and short synacthen test (SST) have been
      validated as safe alternatives to the insulin tolerance test for the assessment
      of the GH reserve and hypothalamic-pituitary-adrenal axis integrity,
      respectively. However, these two tests are usually performed separately. The
      objective was to see whether the synacthen and GHRH/arginine tests could be
      combined to save time and blood samples and minimize inconvenience to patients.
      PATIENTS/METHODS: Twenty-four consecutive patients with adult onset pituitary
      disease requiring pituitary function testing were randomized to receive
      sequentially and in random order a SST, a GHRH/arginine test, and a combined SST
      and GHRH/arginine test on three different visits separated by at least 1 wk.
      RESULTS: There was no difference in basal cortisol or ACTH values for the SST
      done alone or during the combined test. However, when GHRH/arginine was given
      with synacthen, patients had a lower peak cortisol response with a mean
      difference of 116 nmol/liter (95% confidence interval, 52.54 to 179.37; P <
      0.001), and one patient with a normal response on the SST had a subnormal
      cortisol response in the combined test. Similar lower peak cortisol responses
      were observed in males and females with combined test. The difference between the
      peak cortisol responses showed no significant correlation with age (r = 0.123; P
      = 0.58) or with the body mass index (r = -0.376; P = 0.09). There was no
      difference in GH measurements between the GHRH/arginine test done alone or in
      combination with the SST. CONCLUSIONS: Combining the SST and GHRH/arginine test
      results in a lower cortisol response to synacthen. For this reason, the combined
      test cannot be recommended to assess the integrity of cortisol and GH reserve
      using current diagnostic criteria.

PMID- 17192290
TI  - Longitudinal assessment of maternal endothelial function and markers of
      inflammation and placental function throughout pregnancy in lean and obese
      mothers.
AB  - BACKGROUND: Obesity in pregnancy is increasing and is a risk factor for metabolic
      pathology such as preeclampsia. In the nonpregnant, obesity is associated with
      dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. AIM: Our
      aim was to measure microvascular endothelial function in lean and obese pregnant
      women at intervals throughout their pregnancies and at 4 months after delivery.
      Plasma markers of endothelial function, inflammation, and placental function and
      their association with microvascular function were also assessed. METHODS: Women
      in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI)
      less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched
      for age, parity, and smoking status. In vivo endothelial-dependent and 
      independent microvascular function was measured using laser Doppler imaging in
      the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma
      markers of endothelial activation [soluble intercellular cell adhesion molecule-1
      (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand
      factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6,
      TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2
      ratio) were also assessed at each time point. RESULTS: The pattern of improving
      endothelial function during pregnancy was the same for lean and obese, but
      endothelial-dependent vasodilation was significantly lower (P < 0.05) in the
      obese women at each trimester (51, 41, and 39%, respectively). In the postpartum
      period, the improvement in endothelial-dependent vasodilation persisted in the
      lean women but declined to near 1st trimester levels in the obese (lean/obese
      difference, 115%; P < 0.01). There was a small but significant difference in
      endothelial-independent vasodilation between the two groups, lean response being
      greater than obese (P = 0.021), and response declined in both groups in the
      postpartum period. In multivariate analysis, time of sampling had the most impact
      on endothelial-independent function [18.5% (adjusted sum of squares expressed as
      a percentage of total means squared), P < 0.001 for sodium nitroprusside
      response; 9.8%, P < 0.001 for acetylcholine response], and obesity had the most
      impact on endothelial-dependent microvascular function (1.7%, P = 0.046 for
      sodium nitroprusside response; 19.3%, P < 0.001 for acetylcholine response). Time
      of sampling (11.2%, P < 0.001), IL-6 (4.0%, P = 0.002), and IL-10 (2.4%, P =
      0.018) were significant independent contributors to variation in endothelial
      dependent microvascular function. When obesity was entered into the model, the
      association with IL-6 and IL-10 was no longer significant, and obesity explained
      6.8% (P < 0.001) of the variability in endothelial-dependent microvascular
      function. In the 1st trimester, obese women had a significantly higher PAI-1/PAI
      2 ratio [obese median (interquartile range), 0.87 (0.54-1.21) vs. lean 0.30 (0.21
      0.47), P < 0.001), reflecting the lower PAI-2 levels in obese pregnant women. In
      a multivariate analysis, 1st trimester BMI (7.6%, P = 0.012), IL-10 (8.2%, P <
      0.001), and sVCAM-1 (0.73%, P = 0.007) contributed to the 1st trimester PAI-1/PAI
      2 ratio. CONCLUSION: Obese mothers have a lower endothelium-dependent and 
      independent vasodilation when compared with lean counterparts. There was a higher
      PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in
      pregnancy. Obese pregnancy is associated with chronic preexisting endothelial
      activation and impairment of endothelial function secondary to increased
      production of inflammatory T-helper cells-2 cytokines.

PMID- 17192291
TI  - Total and high-molecular-weight adiponectin in breast cancer: in vitro and in
      vivo studies.
AB  - BACKGROUND: Obesity is a major risk factor for breast cancer. We hypothesized
      that obesity-induced decreases in total and/or high-molecular-weight (HMW)
      adiponectin levels may underlie this association. METHODS: We measured serum
      total and HMW adiponectin in a hospital-based case-control study of 74 female
      breast cancer patients and 76 controls. In parallel, expression of adiponectin
      and its receptors AdipoR1/R2 were measured in tissue samples using RT-PCR, and
      protein expression of AdipoR1/R2 was localized and quantified using
      immunohistochemistry. Finally, we documented AdipoR1/R2 expression in several
      breast cancer cell lines and studied adiponectin signaling and the effect of
      adiponectin on proliferation in the T47D breast cancer cell line in vitro.
      RESULTS: Women with the highest adiponectin levels had a 65% reduced risk of
      breast cancer (P = 0.04). This association became stronger after adjustment for
      age, body mass index, and hormonal and reproductive factors (P = 0.02). Modeling
      HMW instead of total adiponectin produced similar results and did not offer any
      additional predictive value. Breast cancer cells expressed AdipoR1/R2 but not
      adiponectin. Expression of AdipoR1, but not AdipoR2, was higher in tumor tissue
      than both adjacent and control tissues. Exposure of T47D cells to adiponectin
      significantly inhibited the percentage of viable cells to 86% and proliferation
      to 66% but had no effect on apoptosis. These effects were associated with
      activation of ERK1/2 but not AMP-activated protein kinase or p38MAPK. CONCLUSION:
      These studies suggest that adiponectin may act as a biomarker of carcinogenesis
      and may constitute a molecular link between obesity and breast cancer.

PMID- 17192292
TI  - Follicular phase dynamics with combined aromatase inhibitor and follicle
      stimulating hormone treatment.
AB  - OBJECTIVE: The objective of this study was to evaluate follicular phase
      parameters during ovarian stimulation with FSH alone or with the aromatase
      inhibitor letrozole. METHODS: Two groups of women undergoing intrauterine
      insemination (IUI): group I (389 patients; mean age 35 +/- 4.3 yr) underwent 630
      IUI cycles stimulated with letrozole and FSH; and group II (134 patients; mean
      age 36.0 +/- 4.6 yr) underwent 166 IUI cycles stimulated with FSH only. Each
      group was stratified into ovulatory and anovulatory cycles. Patients were
      monitored by ultrasound for folliculometry and blood sampling for hormonal assay
      on d 3, 7, 9, or 10 of the cycle, and on the day of human chorionic gonadotropin
      administration. RESULTS: Group I had a significantly lower follicular count
      greater than 10 mm on d 7, greater than 12 mm on d 9 or 10, and greater than 15
      mm on the day of human chorionic gonadotropin administration compared to group II
      (P = 0.006, <0.001, and <0.001, respectively). After stratifying patients by
      diagnosis, this relationship was maintained only for patients with ovulatory
      infertility (P = 0.003, <0.001, and <0.001, respectively). Serum estradiol (E2)
      was significantly lower in the group I ovulatory and anovulatory at the last
      three monitoring visits (P < 0.001). However, the difference in E2 levels
      decreased in the preovulatory period with similar E2 levels per mature follicle.
      No premature preovulatory progesterone rise was observed in either group.
      However, significantly lower progesterone levels were observed in the second half
      of the follicular phase in group I (P = 0.02 and <0.001). Endometrial thickness
      was significantly lower in group I at the second and third visits (P < 0.001,
      0.01) but was comparable to group II at the last monitoring visit. Although, the
      pregnancy rates were similar between the two groups, the multiple pregnancy rate
      was significantly higher in the FSH-only group (P = 0.039). CONCLUSION: The
      addition of letrozole modifies the follicular, hormonal, and endometrial dynamics
      of FSH-stimulated cycles with possible positive effects on the overall cycle
      outcome.

PMID- 17192293
TI  - Antithyroid drugs inhibit thyroid hormone receptor-mediated transcription.
AB  - CONTEXT: Methimazole (MMI) and propylthiouracil (PTU) are widely used as
      antithyroid drugs (ATDs) for the treatment of Graves' disease. Both MMI and PTU
      reduce thyroid hormone levels by several mechanisms, including inhibition of
      thyroid hormone synthesis and secretion. In addition, PTU decreases 5'
      deiodination of T(4) in peripheral tissues. ATDs may also interfere with T(3)
      binding to nuclear thyroid hormone receptors (TRs). However, the effect of ATDs
      on the transcriptional activities of T(3) mediated by TRs has not been studied.
      OBJECTIVE: The present study was undertaken to determine whether ATDs have an
      effect on the gene transcription regulated by T(3) and TRs in vitro. METHODS:
      Transient gene expression experiments and GH secretion assays were performed. To
      elucidate possible mechanisms of the antagonistic action of ATDs, the interaction
      between TR and nuclear cofactors was examined. RESULTS: In the transient gene
      expression experiments, both MMI and PTU significantly suppressed transcriptional
      activities mediated by the TR and T(3) in a dose-dependent manner. In mammalian
      two-hybrid assays, both drugs recruited one of the nuclear corepressors, nuclear
      receptor corepressor, to the TR in the absence of T(3). In addition, PTU
      dissociated nuclear coactivators, such as steroid receptor coactivator-1 and
      glucocorticoid receptor interacting protein-1, from the TR in the presence of
      T(3). Finally, MMI decreased the GH release that was stimulated by T(3).
      CONCLUSIONS: ATDs inhibit T(3) action by recruitment of transcriptional
      corepressors and/or dissociation of coactivators. This is the first report to
      show that ATDs can modulate T(3) action at the transcriptional level.

PMID- 17192294
TI  - Long-term treatment with recombinant insulin-like growth factor (IGF)-I in
      children with severe IGF-I deficiency due to growth hormone insensitivity.
AB  - CONTEXT: Children with severe IGF-I deficiency due to congenital or acquired
      defects in GH action have short stature that cannot be remedied by GH treatment.
      OBJECTIVES: The objective of the study was to examine the long-term efficacy and
      safety of recombinant human IGF-I (rhIGF-I) therapy for short children with
      severe IGF-I deficiency. DESIGN: Seventy-six children with IGF-I deficiency due
      to GH insensitivity were treated with rhIGF-I for up to 12 yr under a
      predominantly open-label design. SETTING: The study was conducted at general
      clinical research centers and with collaborating endocrinologists. SUBJECTS:
      Entry criteria included: age older than 2 yr, sd scores for height and
      circulating IGF-I concentration less than -2 for age and sex, and evidence of
      resistance to GH. INTERVENTION: rhIGF-I was administered sc in doses between 60
      and 120 microg/kg twice daily. MAIN OUTCOME MEASURES: Height velocity, skeletal
      maturation, and adverse events were measured. RESULTS: Height velocity increased
      from 2.8 cm/yr on average at baseline to 8.0 cm/yr during the first year of
      treatment (P < 0.0001) and was dependent on the dose administered. Height
      velocities were lower during subsequent years but remained above baseline for up
      to 8 yr. The most common adverse event was hypoglycemia, which was observed both
      before and during therapy. It was reported by 49% of treated subjects. The next
      most common adverse events were injection site lipohypertrophy (32%) and
      tonsillar/adenoidal hypertrophy (22%). CONCLUSIONS: Treatment with rhIGF-I
      stimulates linear growth in children with severe IGF-I deficiency due to GH
      insensitivity. Adverse events are common but are rarely of sufficient severity to
      interrupt or modify treatment.

PMID- 17192295
TI  - P450c17 deficiency: clinical and molecular characterization of six patients.
AB  - CONTEXT: The characteristics of P450c17 deficiency include 46,XY disorder of sex
      development, hypertension, hypokalemia, and lack of pubertal development.
      OBJECTIVE: To better understand this rare enzymatic deficiency, we analyzed the
      CYP17A1 gene in six affected patients. DESIGN AND PATIENTS: We examined six
      patients, five 46,XY, and one 46,XX (age 9-29 yr) with complete lack of
      masculinization (female infantile external genitalia, no uterus) and delayed
      puberty, respectively, and different degrees of hypertension. MAIN OUTCOME
      MEASUREMENTS: Genotype-phenotype correlation was measured. RESULTS: Four
      homozygote mutations were identified by direct sequencing of the CYP17A1 gene
      corresponding to an alanin 302-proline (A302P) exchange; the loss of lysine 327
      (K327del); the deletion of glutamate 331 (E331del); and the replacement of
      arginine 416 with a histidine (R416H). Both P450c17 activities were abolished in
      all the mutant proteins, except one, when expressed in COS1 cells. The E331del
      mutated P450c17 retained 17alpha-hydroxylase activity. The mutant proteins were
      normally expressed, suggesting that the loss of enzymatic activity is not due to
      defects of synthesis, stability, or localization of P450c17 proteins. CONCLUSION:
      These studies confirm lack of masculinization in 46,XY individuals as the
      pathognomic sign of the complete P450c17 deficiency. In XX individuals P450c17
      deficiency should be considered in cases of delayed puberty. Age of onset and the
      severity of hypertension do not seem to be constant. Careful examination of long
      term follow-ups in two of our patients suggested to us that estrogen treatment in
      P450c17-deficient patients might worsen the enzymatic defect, leading to
      aggravation of the hypertension.

PMID- 17192296
TI  - Changes in body composition in women over six years at midlife: ovarian and
      chronological aging.
AB  - CONTEXT: Understanding the menopause association with body weight is important
      because excess weight increases risk for stroke, incident cardiovascular disease,
      cardiovascular mortality, and all-cause mortality among the middle-aged.
      OBJECTIVE: The objective of this study was to examine chronological age and
      ovarian age and consider how these could influence body size and composition in
      midlife women. DESIGN AND SETTING: The Study of Women's Health Across the Nation
      is a longitudinal, community-based study. This report uses data from the Michigan
      Study of Women's Health Across the Nation site. PARTICIPANTS: Participants were
      543 premenopausal or early perimenopausal African-American and Caucasian women
      aged 42-52 yr at baseline examination. MAIN OUTCOME MEASURES: Waist
      circumference, fat mass and skeletal muscle mass, from bioelectrical impedance,
      were assessed in seven annual serial measures. Annual FSH values were assayed by
      ELISA. The final menstrual period was defined retrospectively after 12 months of
      amenorrhea. RESULTS: There was an absolute cumulative 6-yr increase in fat mass
      of 3.4 kg and a 6-yr decrease in skeletal muscle mass of approximately 0.23 kg.
      There was an absolute cumulative 6-yr increase of approximately 5.7 cm in waist
      circumference. The (log)FSH change was positively correlated with (log)(fat mass)
      change. Waist circumference increased over the time period, but 1 yr after final
      menstrual period, the rate of increase slowed. Fat mass continued to increase
      with no change in rate. CONCLUSIONS: Both time (chronological aging) and ovarian
      aging contributed to substantial changes in body composition (fat and skeletal
      muscle mass) and waist circumference. These changes have important ramifications
      for establishing a metabolic environment that can be healthy or unhealthy.

PMID- 17192297
TI  - Single nucleotide polymorphisms of the melanocortin-3 receptor gene are
      associated with substrate oxidation and first-phase insulin secretion in
      offspring of type 2 diabetic subjects.
AB  - CONTEXT: The melanocortin-3 receptor (MC3R) is a part of the melanocortin system
      that regulates appetite and energy metabolism. The Thr/Thr 6 and Val/Val81
      [corrected] polymorphisms of the MC3R gene have been previously associated with
      high insulin levels and obesity in children. OBJECTIVE: The objective was to
      determine whether single nucleotide polymorphisms (SNPs) of MC3R are associated
      with glucose, lipid, and energy metabolism. DESIGN, SETTING, AND PARTICIPANTS: We
      screened the Lys/Thr6 and Ile/Val81 mutations and six noncoding SNPs of MC3R in a
      cross-sectional study of 216 middle-aged nondiabetic Finnish subjects who were
      offspring of type 2 diabetic patients. MAIN OUTCOME MEASURES: Insulin secretion
      was evaluated by an iv glucose tolerance test, and insulin sensitivity and energy
      metabolism by the hyperinsulinemic euglycemic clamp and indirect calorimetry.
      RESULTS: Carriers of the Lys 6 and Ile 81 [corrected] alleles had significantly
      lower rates of lipid oxidation [0.85 +/- 0.38 vs. 1.00 +/- 0.43 mg/kg of lean
      body mass (LBM)/min; P = 0.022, adjusted for sex, body mass index, age, and
      family relationship] and higher rates of glucose oxidation in the fasting state
      (11.28 +/- 4.64 vs. 9.71 +/- 4.53 micromol/kg of LBM/min; P = 0.031) than
      subjects with the Thr/Thr 6 and Val/Val 81 [corrected] genotypes. They had lower
      rates of lipid oxidation during the hyperinsulinemic clamp (0.32 +/- 0.41 vs.
      0.44 +/- 0.34 mg/kg of LBM/min; P = 0.021) and higher insulin levels in an iv
      glucose tolerance test (insulin under the curve during the first 10 min, 3220 +/-
      1765 vs. 2454 +/- 1538 pmol/liter.min; P = 0.025) compared to subjects with the
      common genotypes. CONCLUSIONS: Our results suggest that SNPs of MC3R may regulate
      substrate oxidation and first-phase insulin secretion.

PMID- 17192298
TI  - The effect of growth hormone on the response of total and acylated ghrelin to a
      standardized oral glucose load and insulin resistance in children with Prader
      Willi syndrome.
AB  - CONTEXT: Fasting levels of plasma ghrelins are grossly elevated in children with
      Prader-Willi syndrome (PWS). The cause of this elevation and the regulation of
      ghrelins in PWS is largely unknown. The regulatory role of individual nutritional
      components and of GH is not well characterized. OBJECTIVE: We investigated the
      influence of GH on acylated (aGhr) and total ghrelin (tGhr) concentrations before
      and after an oral glucose load, and on insulin resistance in PWS children.
      DESIGN, PATIENTS, AND INTERVENTIONS: In a clinical follow-up study, plasma
      ghrelins were measured during an oral glucose tolerance test, and parameters of
      insulin resistance were determined in 28 PWS children before and/or 1.18 (0.42
      9.6) yr (median, range) after start of GH therapy (0.035 mg/kg body weight per
      day). MAIN OUTCOME MEASURES: Fasting and postglucose concentrations of aGhr and
      tGhr and homeostasis model assessment 2 insulin resistance were the main outcome
      measures. SETTING: The study was conducted in a single center (University
      Children's Hospital). RESULTS: High fasting [1060 +/- 292 (sd) pg/ml; n = 12] and
      postglucose trough (801 +/- 303 pg/ml; n = 10) tGhr concentrations in GH
      untreated PWS children were found to be decreased in the GH-treated group
      (fasting 761 +/- 247 pg/ml, n = 24, P = 0.006; postglucose 500 +/- 176 pg/ml, n =
      20; P = 0.006). In contrast, aGhr concentrations and insulin resistance were not
      changed by GH treatment. Both aGhr and tGhr concentrations were decreased by oral
      carbohydrate administration, independent of the GH treatment status. CONCLUSIONS:
      Our results indicate that, in PWS children, aGhr and tGhr are differentially
      regulated by GH.

PMID- 17192299
TI  - Clinical significance of the parental origin of the X chromosome in turner
      syndrome.
AB  - CONTEXT: The phenotype in Turner syndrome (TS) is variable, even in patients with
      a supposedly nonmosaic karyotype. Previous work suggested that there were X
      linked parent-of-origin effects on the phenotype. HYPOTHESIS: The TS phenotype is
      influenced by the parental origin of the missed X chromosome. DESIGN: This was a
      multicenter prospective study of TS patients and both their parents, determining
      parental origin of the X-chromosome, and characterizing the clinical phenotype.
      PATIENTS AND METHODS: Eighty-three TS patients and their parents were studied.
      Inclusion criteria were TS with karyotype 45,X or 46Xi(Xq). Four highly
      polymorphic microsatellite markers on the X-chromosome DMD49, DYSII, DXS1283, and
      the androgen receptor gene and three Y chromosome markers, SRY, DYZ1, and DYZ3.
      OUTCOME MEASURES: The study determined the correlation between the parental
      origin of the X chromosome and the unique phenotypic traits of TS including
      congenital malformations, anthropometry and growth pattern, skeletal defects,
      endocrine traits, education, and vocation. RESULTS: Eighty-three percent of 45,X
      retained their maternal X (X(m)), whereas 64% 46Xi(Xq) retained their paternal X
      (X(p), P < 0.001). Kidney malformations were exclusively found in X(m) patients
      (P = 0.030). The X(m) group had lower total and low-density lipoprotein
      cholesterol (P < 0.003), and higher body mass index sd score (P = 0.030) that was
      not maintained after GH treatment. Response to GH therapy was comparable. Ocular
      abnormalities were more common in the paternal X group (P = 0.017), who also had
      higher academic achievement. CONCLUSIONS: The parental origin of the missing
      short arm of the X chromosome has an impact on overweight, kidney, eye, and
      lipids, which suggests a potential effect of an as-yet-undetermined X chromosome
      gene imprinting.

PMID- 17192300
TI  - The fitness cost of mutations associated with human immunodeficiency virus type 1
      drug resistance is modulated by mutational interactions.
AB  - It is generally accepted that the fitness cost of resistance mutations plays a
      role in the persistence of transmitted drug-resistant human immunodeficiency
      virus type 1 and that mutations that confer a high fitness cost are less able to
      persist in the absence of drug pressure. Here, we show that the fitness cost of
      reverse transcriptase (RT) mutations can vary within a 72-fold range. We also
      demonstrate that the fitness cost of M184V and K70R can be decreased or enhanced
      by other resistance mutations such as D67N and K219Q. We conclude that the
      persistence of transmitted RT mutants might range widely on the basis of fitness
      and that the modulation of fitness cost by mutational interactions will be a
      critical determinant of persistence.

PMID- 17192301
TI  - Reduced apoptosis in human intestinal cells cured of persistent poliovirus
      infection.
AB  - Cells cured of persistent virus infection can be used to investigate cellular
      pathways of resistance to viral cytopathic effects. Persistent poliovirus (PV)
      infections were established in human intestinal Caco-2 cells, and spontaneously
      cured cell cultures were obtained. Two cell clones, cl6 and b13, cured of type 3
      PV mutant infection and their parental Caco-2 cells were compared for
      susceptibility to PV infection, PV receptor CD155 expression, capacity to
      differentiate into polarized enterocytes, and PV-, staurosporine-, and
      actinomycin D-induced apoptosis. Our results strongly suggest that cells that are
      partially resistant to apoptosis can be selected during persistent virus
      infection.

PMID- 17192302
TI  - Sequence-independent targeting of transmembrane proteins synthesized within
      vaccinia virus factories to nascent viral membranes.
AB  - The primary membrane of vaccinia virus, as well as those of other poxviruses,
      forms within a discrete cytoplasmic factory region. We recently determined the
      existence of an operative pathway from the endoplasmic reticulum within the virus
      factory to nascent viral membranes and demonstrated that a viral protein could be
      diverted from this pathway to Golgi membranes by the addition of COPII-binding
      sites (M. Husain, A. S. Weisberg, and B. Moss, Proc. Natl. Acad. Sci. USA,
      103:19506-19511, 2006). Here we describe an investigation of the structural
      features that are required for transit of proteins to the viral membrane.
      Deletion of either the N-terminal domain or the C-terminal cytoplasmic tail from
      the conserved A9 protein did not prevent its incorporation into viral membranes,
      whereas deletion of the transmembrane domain resulted in its distribution
      throughout the cytoplasm. Nevertheless, replacement of the A9 transmembrane
      domain with the corresponding region of a nonpoxvirus transmembrane protein or of
      a vaccinia virus extracellular envelope protein allowed viral membrane targeting,
      indicating no requirement for a specific amino acid sequence. Remarkably, the
      epitope-tagged A9 transmembrane domain alone, as well as a heterologous
      transmembrane domain lacking a poxvirus sequence, was sufficient for viral
      membrane association. The data are consistent with a sequence-independent pathway
      in which transmembrane proteins that are synthesized within the virus factory and
      lack COPII or other binding sites that enable conventional endoplasmic reticulum
      exiting are incorporated into nascent viral membranes.

PMID- 17192303
TI  - Complete genome analysis of 33 ecologically and biologically diverse Rift Valley
      fever virus strains reveals widespread virus movement and low genetic diversity
      due to recent common ancestry.
AB  - Rift Valley fever (RVF) virus is a mosquito-borne RNA virus responsible for large
      explosive outbreaks of acute febrile disease in humans and livestock in Africa
      with significant mortality and economic impact. The successful high-throughput
      generation of the complete genome sequence was achieved for 33 diverse RVF virus
      strains collected from throughout Africa and Saudi Arabia from 1944 to 2000,
      including strains differing in pathogenicity in disease models. While several
      distinct virus genetic lineages were determined, which approximately correlate
      with geographic origin, multiple exceptions indicative of long-distance virus
      movement have been found. Virus strains isolated within an epidemic (e.g.,
      Mauritania, 1987, or Egypt, 1977 to 1978) exhibit little diversity, while those
      in enzootic settings (e.g., 1970s Zimbabwe) can be highly diverse. In addition,
      the large Saudi Arabian RVF outbreak in 2000 appears to have involved virus
      introduction from East Africa, based on the close ancestral relationship of a
      1998 East African virus. Virus genetic diversity was low (approximately 5%) and
      primarily involved accumulation of mutations at an average of 2.9 x 10(-4)
      substitutions/site/year, although some evidence of RNA segment reassortment was
      found. Bayesian analysis of current RVF virus genetic diversity places the most
      recent common ancestor of these viruses in the late 1800s, the colonial period in
      Africa, a time of dramatic changes in agricultural practices and introduction of
      nonindigenous livestock breeds. In addition to insights into the evolution and
      ecology of RVF virus, these genomic data also provide a foundation for the design
      of molecular detection assays and prototype vaccines useful in combating this
      important disease.

PMID- 17192304
TI  - Tropism modification of adenovirus vectors by peptide ligand insertion into
      various positions of the adenovirus serotype 41 short-fiber knob domain.
AB  - Recombinant adenoviruses have emerged as promising agents in therapeutic gene
      transfer, genetic vaccination, and viral oncolysis. Therapeutic applications of
      adenoviruses, however, would benefit substantially from targeted virus cell
      entry, for example, into cancer or immune cells, as opposed to the broad tropism
      that adenoviruses naturally possess. Such tropism modification of adenoviruses
      requires the deletion of their natural cell binding properties and the
      incorporation of cell binding ligands. The short fibers of subgroup F
      adenoviruses have recently been suggested as a tool for genetic adenovirus
      detargeting based on the reduced infectivity of corresponding adenovectors with
      chimeric fibers in vitro and in vivo. The goal of our study was to determine
      functional insertion sites for peptide ligands in the adenovirus serotype 41
      (Ad41) short fiber knob. With a model peptide, CDCRGDCFC, we could demonstrate
      that ligand incorporation into three of five analyzed loops of the knob, namely,
      EG, HI, and IJ, is feasible without a loss of fiber trimerization. The resulting
      adenovectors showed enhanced infectivity for various cell types, which was
      superior to that of viruses with the same peptide fused to the fiber C terminus.
      Strategies to further augment gene transfer efficacy by extension of the fiber
      shaft, insertion of tandem copies of the ligand peptide, or extension of the
      ligand-flanking linkers failed, indicating that precise ligand positioning is
      pivotal. Our study establishes that internal ligand incorporation into a short
      shafted adenovirus fiber is feasible and suggests the Ad41 short fiber with
      ligand insertion into the top (IJ loop) or side (EG and HI loops) of the knob
      domain as a novel platform for genetic targeting of therapeutic adenoviruses.

PMID- 17192305
TI  - Caspase 3-dependent cell death of neurons contributes to the pathogenesis of West
      Nile virus encephalitis.
AB  - West Nile virus (WNV) is a neurotropic, arthropod-borne flavivirus that has
      become a significant global cause of viral encephalitis. To examine the
      mechanisms of WNV-induced neuronal death and the importance of apoptosis in
      pathogenesis, we evaluated the role of a key apoptotic regulator, caspase 3. WNV
      infection induced caspase 3 activation and apoptosis in the brains of wild-type
      mice. Notably, congenic caspase 3(-/-) mice were more resistant to lethal WNV
      infection, although there were no significant differences in the tissue viral
      burdens or the kinetics of viral spread. Instead, decreased neuronal death was
      observed in the cerebral cortices, brain stems, and cerebella of caspase 3(-/-)
      mice. Analogously, primary central nervous system (CNS)-derived neurons
      demonstrated caspase 3 activation and apoptosis after WNV infection, and
      treatment with caspase inhibitors or a genetic deficiency in caspase 3
      significantly decreased virus-induced death. These studies establish that caspase
      3-dependent apoptosis contributes to the pathogenesis of lethal WNV encephalitis
      and suggest possible novel therapeutic targets to restrict CNS injury.

PMID- 17192306
TI  - Phylogenetic analysis of feline immunodeficiency virus in feral and companion
      domestic cats of New Zealand.
AB  - Nested PCR was used to amplify envelope V3-V6 gene fragments of feline
      immunodeficiency virus (FIV) from New Zealand cats. Phylogenetic analyses
      established that subtypes A and C predominate among New Zealand cats, with clear
      evidence of intersubtype recombination. In addition, 17 sequences were identified
      that were distinct from all known FIV clades, and we tentatively suggest these
      belong to a novel subtype.

PMID- 17192307
TI  - Aurintricarboxylic acid inhibits the early stage of vaccinia virus replication by
      targeting both cellular and viral factors.
AB  - Aurintricarboxylic acid (ATA) has been shown to inhibit the replication of
      viruses from several different families, including human immunodeficiency virus,
      vesicular stomatitis virus, and the coronavirus causing severe acute respiratory
      syndrome. This study characterizes the inhibitory effect of ATA on vaccinia virus
      replication in HeLa, Huh7, and AD293 cells. Vaccinia virus replication is
      significantly abrogated upon ATA treatment, which is associated with the
      inhibition of early viral gene transcription. This inhibitory effect may be
      attributed to two findings. First, ATA blocks the phosphorylation of
      extracellular signal-regulated kinase 1/2, an event shown to be essential for
      vaccinia virus replication. Second, ATA inhibits the phosphatase activity of the
      viral enzyme H1L, which is required to initiate viral transcription. Thus, ATA
      inhibits vaccinia virus replication by targeting both cellular and viral factors
      essential for the early stage of replication.

PMID- 17192308
TI  - Identification and characterization of peptides that interact with hepatitis B
      virus via the putative receptor binding site.
AB  - A direct involvement of the PreS domain of the hepatitis B virus (HBV) large
      envelope protein, and in particular amino acid residues 21 to 47, in virus
      attachment to hepatocytes has been suggested by many previous studies. Several
      PreS-interacting proteins have been identified. However, they share few common
      sequence motifs, and a bona fide cellular receptor for HBV remains elusive. In
      this study, we aimed to identify PreS-interacting motifs and to search for novel
      HBV-interacting proteins and the long-sought receptor. PreS fusion proteins were
      used as baits to screen a phage display library of random peptides. A group of
      PreS-binding peptides were obtained. These peptides could bind to amino acids 21
      to 47 of PreS1 and shared a linear motif (W1T2X3W4W5) sufficient for binding
      specifically to PreS and viral particles. Several human proteins with such a
      motif were identified through BLAST search. Analysis of their biochemical and
      structural properties suggested that lipoprotein lipase (LPL), a key enzyme in
      lipoprotein metabolism, might interact with PreS and HBV particles. The
      interaction of HBV with LPL was demonstrated by in vitro binding, virus capture,
      and cell attachment assays. These findings suggest that LPL may play a role in
      the initiation of HBV infection. Identification of peptides and protein ligands
      corresponding to LPL that bind to the HBV envelope will offer new therapeutic
      strategies against HBV infection.

PMID- 17192309
TI  - Cytomegalovirus primary envelopment occurs at large infoldings of the inner
      nuclear membrane.
AB  - We have investigated the morphogenesis of human and murine cytomegalovirus by
      transmission electron microscopy after high-pressure freezing, freeze
      substitution, and plastic embedding. We observed large tubular infoldings of the
      inner nuclear membrane that were free of lamina and active in primary envelopment
      and subsequent transport of capsids to the nuclear periphery. Semiquantitative
      determinations of the enlarged inner nuclear membrane area and the location of
      the primary envelopment of nucleocapsids demonstrated that this structure
      represents a virus-induced specialized membrane domain at which the particles are
      preferentially enveloped. This is a previously undescribed structural element
      relevant in cytomegalovirus morphogenesis.

PMID- 17192310
TI  - Conserved determinants for membrane association of nonstructural protein 5A from
      hepatitis C virus and related viruses.
AB  - Nonstructural protein 5A (NS5A) is a membrane-associated essential component of
      the hepatitis C virus (HCV) replication complex. An N-terminal amphipathic alpha
      helix mediates in-plane membrane association of HCV NS5A and at the same time is
      likely involved in specific protein-protein interactions required for the
      assembly of a functional replication complex. The aim of this study was to
      identify the determinants for membrane association of NS5A from the related GB
      viruses and pestiviruses. Although primary amino acid sequences differed
      considerably, putative membrane anchor domains with amphipathic features were
      predicted in the N-terminal domains of NS5A proteins from these viruses. Confocal
      laser scanning microscopy, as well as membrane flotation analyses, demonstrated
      that NS5As from GB virus B (GBV-B), GBV-C, and bovine viral diarrhea virus, the
      prototype pestivirus, display membrane association characteristics very similar
      to those of HCV NS5A. The N-terminal 27 to 33 amino acid residues of these NS5A
      proteins were sufficient for membrane association. Circular dichroism analyses
      confirmed the capacity of these segments to fold into alpha helices upon
      association with lipid-like molecules. Despite structural conservation, only very
      limited exchanges with sequences from related viruses were tolerated in the
      context of functional HCV RNA replication, suggesting virus-specific interactions
      of these segments. In conclusion, membrane association of NS5A by an N-terminal
      amphipathic alpha helix is a feature shared by HCV and related members of the
      family Flaviviridae. This observation points to conserved roles of the N-terminal
      amphipathic alpha helices of NS5A in replication complex formation.

PMID- 17192312
TI  - Suppression of the Sendai virus M protein through a novel short interfering RNA
      approach inhibits viral particle production but does not affect viral RNA
      synthesis.
AB  - Short RNA interference is more and more widely recognized as an effective method
      to specifically suppress viral functions in eukaryotic cells. Here, we used an
      experimental system that allows suppression of the Sendai virus (SeV) M protein
      by using a target sequence, derived from the green fluorescent protein gene, that
      was introduced in the 3' untranslated region of the M protein mRNA. Silencing of
      the M protein gene was eventually achieved by a small interfering RNA (siRNA)
      directed against this target sequence. This siRNA was constitutively expressed in
      a cell line constructed by transduction with an appropriate lentivirus vector.
      Suppression of the M protein was sufficient to diminish virus production by 50-
      to 100-fold. This level of suppression had no apparent effect on viral
      replication and transcription, supporting the lack of M involvement in SeV
      transcription or replication control.

PMID- 17192311
TI  - Nuclear import of bovine papillomavirus type 1 E1 protein is mediated by multiple
      alpha importins and is negatively regulated by phosphorylation near a nuclear
      localization signal.
AB  - Papillomavirus DNA replication occurs in the nucleus of infected cells and
      requires the viral E1 protein, which enters the nuclei of host epithelial cells
      and carries out enzymatic functions required for the initiation of viral DNA
      replication. In this study, we investigated the pathway and regulation of the
      nuclear import of the E1 protein from bovine papillomavirus type 1 (BPV1). Using
      an in vitro binding assay, we determined that the E1 protein interacted with
      importins alpha3, alpha4, and alpha5 via its nuclear localization signal (NLS)
      sequence. In agreement with this result, purified E1 protein was effectively
      imported into the nucleus of digitonin-permeabilized HeLa cells after incubation
      with importin alpha3, alpha4, or alpha5 and other necessary import factors. We
      also observed that in vitro binding of E1 protein to all three alpha importins
      was significantly decreased by the introduction of pseudophosphorylation
      mutations in the NLS region. Consistent with the binding defect,
      pseudophosphorylated E1 protein failed to enter the nucleus of digitonin
      permeabilized HeLa cells in vitro. Likewise, the pseudophosphorylation mutant
      showed aberrant intracellular localization in vivo and accumulated primarily on
      the nuclear envelope in transfected HeLa cells, while the corresponding alanine
      replacement mutant displayed the same cellular location pattern as wild-type E1
      protein. Collectively, our data demonstrate that BPV1 E1 protein can be
      transported into the nucleus by more than one importin alpha and suggest that E1
      phosphorylation by host cell kinases plays a regulatory role in modulating E1
      nucleocytoplasmic localization. This phosphoregulation of nuclear E1 protein
      uptake may contribute to the coordination of viral replication with keratinocyte
      proliferation and differentiation.

PMID- 17192313
TI  - Prevalence and abundance of latently transcribed varicella-zoster virus genes in
      human ganglia.
AB  - In human ganglia latently infected with varicella-zoster virus (VZV), sequence
      analysis has revealed that five viral genes (VZV genes 21, 29, 62, 63, and 66)
      are transcribed. However, their comparative prevalence and abundance are unknown.
      Here, using real-time PCR, we analyzed 28 trigeminal ganglia from 14 humans for
      RNA corresponding to the five virus genes known to be transcribed in latently
      infected human ganglia. The most prevalent transcript found was VZV gene 63
      (78%), followed by gene 66 (43%), gene 62 (36%), and gene 29 (21%). No gene 21
      transcripts were detected in any of the 28 ganglia. VZV gene 63 RNA was also the
      most abundant (3,710 +/- 6,895 copies per 1 microg of mRNA) transcript detected
      in latently infected human ganglia, followed by VZV gene 29 (491 +/- 594), VZV
      gene 66 (117 +/- 85), and VZV gene 62 (64 +/- 38). Thus, the repeated detection
      and high abundance of VZV gene 63 transcripts in latently infected ganglia
      suggests that VZV gene 63 may be more important for the maintenance of virus
      latency than the less abundantly transcribed and randomly detected VZV genes 21,
      29, 62, and 66.

PMID- 17192314
TI  - The antiviral efficacy of simian immunodeficiency virus-specific CD8+ T cells is
      unrelated to epitope specificity and is abrogated by viral escape.
AB  - CD8(+) T lymphocytes appear to play a role in controlling human immunodeficiency
      virus (HIV) replication, yet routine immunological assays do not measure the
      antiviral efficacy of these cells. Furthermore, it has been suggested that CD8+ T
      cells that recognize epitopes derived from proteins expressed early in the viral
      replication cycle can be highly efficient. We used a functional in vitro assay to
      assess the abilities of different epitope-specific CD8+ T-cell lines to control
      simian immunodeficiency virus (SIV) replication. We compared the antiviral
      efficacies of 26 epitope-specific CD8+ T-cell lines directed against seven SIV
      epitopes in Tat, Nef, Gag, Env, and Vif that were restricted by either Mamu-A*01
      or Mamu-A*02. Suppression of SIV replication varied depending on the epitope
      specificities of the CD8+ T cells and was unrelated to whether the targeted
      epitope was derived from an early or late viral protein. Tat(28-35)SL8- and
      Gag(181-189)CM9-specific CD8+ T-cell lines were consistently superior at
      suppressing viral replication compared to the other five SIV-specific CD8+ T-cell
      lines. We also investigated the impact of viral escape on antiviral efficacy by
      determining if Tat(28-35)SL8- and Gag(181-189)CM9-specific CD8+ T-cell lines
      could suppress the replication of an escaped virus. Viral escape abrogated the
      abilities of Tat(28-35)SL8- and Gag(181-189)CM9-specific CD8+ T cells to control
      viral replication. However, gamma interferon (IFN-gamma) enzyme-linked immunospot
      and IFN-gamma/tumor necrosis factor alpha intracellular-cytokine-staining assays
      detected cross-reactive immune responses against the Gag escape variant.
      Understanding antiviral efficacy and epitope variability, therefore, will be
      important in selecting candidate epitopes for an HIV vaccine.

PMID- 17192318
TI  - Biomechanical evaluation of 4 techniques of distal biceps brachii tendon repair.
AB  - BACKGROUND: Recent technical improvements have led the way to a resurgence of the
      single-incision approach for repair of distal biceps tendon injuries. There has
      been no biomechanical evaluation of all these techniques with comparison to the
      standard 2-incision bone tunnel technique. HYPOTHESIS: There will be no
      difference under cyclic loading and ultimate failure between the 2-incision bone
      tunnel technique, suture anchor repair, interference screw, and EndoButton
      techniques for the repair of distal biceps tendon ruptures. STUDY DESIGN:
      Controlled laboratory study. METHODS: Sixty-three fresh-frozen cadaveric elbows
      were randomly assigned to 4 treatment groups (bone tunnel, EndoButton, suture
      anchor, interference screw). Cyclic loading was then performed from 0 degrees to
      90 degrees at 0.5 Hz for 3600 cycles with a 50-N load. A differential variable
      reductance transducer was placed between the radius and distal tendon to
      determine displacement. The construct was then pulled to failure at 120 mm/min.
      RESULTS: A multiple analysis of variance revealed no statistically significant
      difference for displacement among the 4 repair techniques. Displacement using the
      bone tunnel was 3.55 mm, EndoButton was 3.42 mm, suture anchor was 2.33 mm, and
      interference screw was 2.15 mm. There was a statistically significant greater
      load to failure with EndoButton (440 N) than suture anchor (381 N), bone tunnel
      (310 N), or interference screw (232 N) (P < .001). CONCLUSION: The EndoButton
      technique had the highest load to failure. CLINICAL RELEVANCE: These data
      demonstrate the EndoButton to be the strongest repair technique, with no failures
      during cycling at physiologic loads and with the largest load to failure. These
      findings are important in maximizing surgical results and stability and suggest
      that the construct can tolerate early postoperative active range of motion.

PMID- 17192316
TI  - Oncolytic vesicular stomatitis virus induces apoptosis via signaling through PKR,
      Fas, and Daxx.
AB  - Matrix (M) protein mutants of vesicular stomatitis virus (VSV) are promising
      oncolytic agents for cancer therapy. Previous research has implicated Fas and PKR
      in apoptosis induced by other viruses. Here, we show that dominant-negative
      mutants of Fas and PKR inhibit M protein mutant virus-induced apoptosis. Most
      previous research has focused on the adapter protein FADD as a necessary
      transducer of Fas-mediated apoptosis. However, the expression of dominant
      negative FADD had little effect on the induction of apoptosis by M protein mutant
      VSV. Instead, virus-induced apoptosis was inhibited by the expression of a
      dominant-negative mutant of the adapter protein Daxx. These data indicate that
      Daxx is more important than FADD for apoptosis induced by M protein mutant VSV.
      These results show that PKR- and Fas-mediated signaling play important roles in
      cell death during M protein mutant VSV infection and that Daxx has novel
      functions in the host response to virus infection by mediating virus-induced
      apoptosis.

PMID- 17192317
TI  - Phase resetting curves and oscillatory stability in interneurons of rat
      somatosensory cortex.
AB  - Synchronous oscillations in neural activity are found over wide areas of the
      cortex. Specific populations of interneurons are believed to play a significant
      role in generating these synchronized oscillations through mutual synaptic and
      gap-junctional interactions. Little is known, though, about the mechanism of how
      oscillations are maintained stably by particular types of interneurons and by
      their local networks. To obtain more insight into this, we measured membrane
      potential responses to small current-pulse perturbations during regular firing,
      to construct phase resetting curves (PRCs) for three types of interneurons:
      nonpyramidal regular-spiking (NPRS), low-threshold spiking (LTS), and fast
      spiking (FS) cells. Within each cell type, both monophasic and biphasic PRCs were
      observed, but the proportions and sensitivities to perturbation amplitude were
      clearly correlated to cell type. We then analyzed the experimentally measured
      PRCs to predict oscillation stability, or firing reliability, of cells for a
      complex stochastic input, as occurs in vivo. To do this, we used a method from
      random dynamical system theory to estimate Lyapunov exponents of the simplified
      phase model on the circle. The results indicated that LTS and NPRS cells have
      greater oscillatory stability (are more reliably entrained) in small noisy inputs
      than FS cells, which is consistent with their distinct types of threshold
      dynamics.

PMID- 17192319
TI  - Results of arthroscopic fixation of osteochondritis dissecans lesion of the knee
      with cylindrical autogenous osteochondral plugs.
AB  - BACKGROUND: In situ fixation of unstable lesions of osteochondral dissecans of
      the knees with cylindrical osteochondral autograft transplantation has been
      reported to provide excellent results with healing of the osteochondral dissecans
      fragment. PURPOSE: To evaluate the clinical results and magnetic resonance
      imaging findings of the osteochondral dissecans of knees treated with in situ
      fixation of the osteochondral fragments with osteochondral autograft
      transplantation. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twelve
      knees (12 patients; mean age, 16.0 years) with osteochondral dissecans lesions
      were treated with in situ fixation with autogenous osteochondral plugs. The mean
      lesion size was 2.4 cm(2) (range, 1.0-4.9 cm(2)). The osteochondral dissecans
      lesions were located on the medial femoral condyle in 10 patients and on the
      lateral femoral condyle in 2 patients. Seven lesions were located in the
      weightbearing area. The International Cartilage Repair Society classification in
      arthroscopic findings was grade II in 1 patient, grade III in 8 patients, and
      grade IV in 3 patients. All patients were evaluated with the Hughston Rating
      Scale form with the mean follow-up at 4.5 years (range, 2.8-5.9 years). The
      interface between the osteochondral fragment and subchondral bone and changes in
      donor site of the osteochondral graft were evaluated with T2-weighted magnetic
      resonance image up to 12 months postoperatively. RESULTS: The Hughston Rating
      Scale scored 8 knees as excellent, 3 as good, and 1 as fair. The interface
      between the osteochondral fragment and subchondral bone had disappeared on
      magnetic resonance image by 3 months postoperatively in all cases. No
      complications arising from the donor site area were observed. Signal intensity of
      donor site changed from high signal preoperatively to homogeneous surrounding
      cancellous bone by 1 year postoperatively. CONCLUSION: Biological fixation of the
      osteochondral dissecans lesion with cylindrical osteochondral autograft provided
      healing of the osteochondral fragments.

PMID- 17192315
TI  - Evolution and molecular epidemiology of H9N2 influenza A viruses from quail in
      southern China, 2000 to 2005.
AB  - H9N2 influenza viruses have become established and maintain long-term endemicity
      in terrestrial poultry in Asian countries. Occasionally these viruses transmit to
      other mammals, including humans. Increasing epidemiological and laboratory
      findings suggest that quail may be an important host, as they are susceptible to
      different subtypes of influenza viruses. To better understand the role of quail
      in influenza virus ecology and evolution, H9N2 viruses isolated from quail during
      2000 to 2005 were antigenically and genetically characterized. Our results showed
      that H9N2 viruses are prevalent year-round in southern China and replicate mainly
      asymptomatically in the respiratory tract of quail. Genetic analysis revealed
      that both the G1-like and Ck/Bei-like H9N2 lineages were cocirculating in quail
      since 2000. Phylogenetic analyses demonstrated that most of the isolates tested
      were double- or multiple-reassortant variants, with four G1-like and 16 Ck/Bei
      like genotypes recognized. A novel genotype of G1-like virus became predominant
      in quail since 2003, while multiple Ck/Bei-like genotypes were introduced into
      quail, wherein they incorporated G1-like gene segments, but none of them became
      established in this host. Those Ck/Bei-like reassortants generated in quail have
      then been introduced into other poultry. These complex interactions form a two
      way transmission system between quail and other types of poultry. The present
      study provides evidence that H9N2 and H5N1 subtype viruses have also exchanged
      gene segments to generate currently circulating reassortants of both subtypes
      that have pandemic potential. Continuing influenza virus surveillance in poultry
      is critical to understanding the genesis and emergence of potentially pandemic
      strains in this region.

PMID- 17192320
TI  - Relationship of chronic ankle instability to muscle activation patterns during
      the transition from double-leg to single-leg stance.
AB  - BACKGROUND: Impaired muscle activation may predispose subjects to develop chronic
      ankle instability. It has been suggested that impairments are found not only in
      structures around the injured ankle but also around the more proximal joint
      complexes. HYPOTHESIS: Subjects with chronic ankle instability were expected to
      show later onset times for lower limb and trunk muscle activation when compared
      with control subjects. They were expected to show less variability in muscle
      activation patterns compared with the control group. STUDY DESIGN: Controlled
      laboratory study. METHODS: Thirty control subjects and 10 subjects with chronic
      ankle instability participated in the study. The onset of muscle activity of 14
      muscles of the lower limb and trunk was measured during the transition from a
      double-leg stance position to a single-leg stance position in eyes-open and eyes
      closed test conditions. RESULTS: Subjects with chronic ankle instability showed
      significantly later onset times for the ankle, hip, and hamstring muscles
      compared with control subjects. They used a similar muscle activation pattern in
      both test conditions, whereas control subjects adjusted their activation pattern
      according to the condition. CONCLUSIONS: Differences in muscle activation
      patterns between subjects with chronic ankle instability and control subjects
      occur not only around the ankle but also around other joints. Subjects with
      chronic ankle instability show less variability in muscle activation patterns
      between test conditions. CLINICAL RELEVANCE: Knowledge of muscle activation
      patterns in the whole lower limb and trunk in noninjured subjects and the
      differences found in chronic ankle instability subjects broadens the physical
      therapy approach to the treatment of chronic ankle instability.

PMID- 17192322
TI  - Eccentric training and an Achilles wrap reduce Achilles tendon capillary blood
      flow and capillary venous filling pressures and increase tendon oxygen saturation
      in insertional and midportion tendinopathy.

PMID- 17192321
TI  - Re: Long-term outcome of endoscopic anterior cruciate ligament reconstruction
      with patellar tendon autograft: minimum 13-year review.

PMID- 17192324
TI  - Rosiglitazone in diabetes control in hemodialysis patients with and without viral
      hepatitis infection: effectiveness and side effects.
AB  - OBJECTIVE: Thiazolidinedione (TZD) may provide an additional benefit of
      cardiovascular protection in diabetic patients through targeting of insulin
      resistance. However, use of a TZD is hampered by possible effects of fluid
      retention and hepatotoxicity. In this study we aimed to determine whether the
      risk of TZD-induced fluid retention or hepatic injury is higher in hemodialysis
      patients with persistent viral hepatitis infection. RESEARCH DESIGN AND METHODS:
      This was a prospective, cohort study on hemodialysis patients. Type 2 diabetic
      patients with A1C levels of >8% were followed for at least 12 months.
      Rosiglitazone was initiated at 2-4 mg/day. The primary outcome was the target A1C
      (<7%) achieved and dosages of rosiglitazone. Secondary outcomes included changes
      in lipid profile and inflammatory biomarkers. Safety evaluations were number of
      hypoglycemic episodes, changes in liver transaminase levels, cardiothoracic ratio
      (CTR), fluid status control during dialysis, and events of symptomatic heart
      failure. RESULTS: A total of 78 patients, including 15.4% (n = 12) hepatitis B
      surface antigen-positive and 16.7% (n = 13) anti-hepatis C virus (HCV)-positive
      patients, were enrolled. The mean follow-up period was 15.4 +/- 3.8 months. The
      diabetic response rate (A1C <7%) to rosiglitazone was 86.1%. The serum
      triglyceride level was reduced (194 +/- 112.5 to 168 +/- 88 mg/dl, P = 0.037)
      more significantly than the total cholesterol level (178 +/- 42.1 to 174 +/- 46.5
      mg/dl, P = 0.13). High-dose rosiglitazone (8 mg/day) reduced the serum level of C
      reactive protein and increased the serum adiponectin level significantly. After
      rosiglitazone, interdialysis weight gain (2.07 +/- 1.6 to 3.2 +/- 1.2 kg, P <
      0.01) and mean CTR (48.2 +/- 5.6 to 50.4 +/- 6.2%, P = 0.0213) of individuals
      increased significantly. Nevertheless, liver aminotransferase (aspartate
      aminotransferase and alanine aminotransferase) levels did not show a tendency to
      increase in patients (n = 25) with viral hepatitis B or C infections.
      CONCLUSIONS: Among regular hemodialysis patients with chronic viral hepatitis
      infections, rosiglitazone may be safely used for diabetes control. However, one
      must be aware that a possible effect of its use is a deterioration in
      cardiovascular reserve.

PMID- 17192325
TI  - The National Cholesterol Education Program - Adult Treatment Panel III,
      International Diabetes Federation, and World Health Organization definitions of
      the metabolic syndrome as predictors of incident cardiovascular disease and
      diabetes.
AB  - OBJECTIVE: The clinical value of metabolic syndrome is uncertain. Thus, we
      examined cardiovascular disease (CVD) and diabetes risk prediction by the
      National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATPIII),
      International Diabetes Federation, and World Health Organization definitions of
      the metabolic syndrome. RESEARCH DESIGN AND METHODS: We analyzed the risks
      associated with metabolic syndrome, the NCEP multiple risk factor categories, and
      2-h glucose values in the San Antonio Heart Study (n = 2,559; age range 25-64
      years; 7.4 years of follow-up). RESULTS: Both ATPIII metabolic syndrome plus age
      > or = 45 years (odds ratio 9.25 [95% CI 4.85-17.7]) and multiple (two or more)
      risk factors plus a 10-year coronary heart disease (CHD) risk of 10-20% (11.9
      [6.00-23.6]) had similar CVD risk in men without CHD, as well as CHD risk
      equivalents. In women counterparts, multiple (two or more) risk factors plus a 10
      year CHD risk of 10-20% was infrequent (10 of 1,254). However, either a 10-year
      CHD risk of 5-20% (7.72 [3.42-17.4]) or ATPIII metabolic syndrome plus age > or =
      55 years (4.98 [2.08-12.0]) predicted CVD. ATPIII metabolic syndrome increased
      the area under the receiver operating characteristic curve of a model containing
      age, sex, ethnic origin, family history of diabetes, and 2-h and fasting glucose
      values (0.857 vs. 0.842, P = 0.013). All three metabolic syndrome definitions
      imparted similar CVD and diabetes risks. CONCLUSIONS: Metabolic syndrome is
      associated with a significant CVD risk, particularly in men aged > or = 45 years
      and women aged > or = 55 years. The metabolic syndrome predicts diabetes beyond
      glucose intolerance alone.

PMID- 17192326
TI  - Preventing diabetic foot ulcer recurrence in high-risk patients: use of
      temperature monitoring as a self-assessment tool.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of a
      temperature monitoring instrument to reduce the incidence of foot ulcers in
      individuals with diabetes who have a high risk for lower extremity complications.
      RESEARCH DESIGN AND METHODS: In this physician-blinded, randomized, 15-month,
      multicenter trial, 173 subjects with a previous history of diabetic foot
      ulceration were assigned to standard therapy, structured foot examination, or
      enhanced therapy groups. Each group received therapeutic footwear, diabetic foot
      education, and regular foot care. Subjects in the structured foot examination
      group performed a structured foot inspection daily and recorded their findings in
      a logbook. If standard therapy or structured foot examinations identified any
      foot abnormalities, subjects were instructed to contact the study nurse
      immediately. Subjects in the enhanced therapy group used an infrared skin
      thermometer to measure temperatures on six foot sites each day. Temperature
      differences >4 degrees F (>2.2 degrees C) between left and right corresponding
      sites triggered patients to contact the study nurse and reduce activity until
      temperatures normalized. RESULTS: The enhanced therapy group had fewer foot
      ulcers than the standard therapy and structured foot examination groups (enhanced
      therapy 8.5 vs. standard therapy 29.3%, P = 0.0046 and enhanced therapy vs.
      structured foot examination 30.4%, P = 0.0029). Patients in the standard therapy
      and structured foot examination groups were 4.37 and 4.71 times more likely to
      develop ulcers than patients in the enhanced therapy group. CONCLUSIONS: Infrared
      temperature home monitoring, in serving as an "early warning sign," appears to be
      a simple and useful adjunct in the prevention of diabetic foot ulcerations.

PMID- 17192328
TI  - Effect of orlistat on weight regain and cardiovascular risk factors following a
      very-low-energy diet in abdominally obese patients: a 3-year randomized, placebo
      controlled study.
AB  - OBJECTIVE: To investigate the efficacy of orlistat on the maintenance of weight
      loss over 3 years following a major weight loss induced by very-low-energy diet
      (VLED) in obese patients with metabolic risk factors such as dyslipidemia,
      impaired fasting glucose, and diet-treated type 2 diabetes. RESEARCH DESIGN AND
      METHODS: Initially, weight loss was induced by an 8-week VLED (600-800 kcal/day)
      in 383 patients with a mean BMI of 37.5 kg/m(2) (range 30.0-45.2). Those who lost
      > or = 5% of their body weight (309 of 383 patients) were then randomized to
      receive lifestyle counseling for 3 years together with either orlistat 120 mg
      t.i.d. or matching placebo capsules. Primary end points were the maintenance of >
      or = 5% weight loss after 3 years. Additionally, differences in the development
      of type 2 diabetes between orlistat and placebo were analyzed. RESULTS: The VLED
      induced a mean weight loss of 14.4 +/- 2.0 kg among the subsequently randomized
      patients. The mean weight gain after 3 years was lower with orlistat than with
      placebo (4.6 +/- 8.6 vs. 7.0 +/- 7.1 kg; P < 0.02). The number of participants
      who achieved > or =5% weight loss also favored orlistat (67 vs. 56%; P = 0.037).
      Waist circumference was significantly more reduced in the orlistat group (P <
      0.05), but no other differences in the risk factors were observed between the two
      groups. The incidences of new cases of type 2 diabetes were significantly reduced
      in the orlistat group (8 cases out of 153 subjects) versus placebo (17 cases out
      of 156 subjects) (P = 0.041). CONCLUSIONS: The addition of orlistat to lifestyle
      intervention was associated with maintenance of an extra 2.4 kg weight loss after
      VLED for up to 3 years in obese subjects. The combination of orlistat and
      lifestyle intervention was associated with a reduced occurrence of type 2
      diabetes.

PMID- 17192327
TI  - Does treatment with duloxetine for neuropathic pain impact glycemic control?
AB  - OBJECTIVE: We examined changes in metabolic parameters in clinical trials of
      duloxetine for diabetic peripheral neuropathic pain (DPNP). RESEARCH DESIGN AND
      METHODS: Data were pooled from three similarly designed clinical trials. Adults
      with diabetes and DPNP (n = 1,024) were randomized to 60 mg duloxetine q.d., 60
      mg b.i.d., or placebo for 12 weeks. Subjects (n = 867) were re-randomized to 60
      mg duloxetine b.i.d. or routine care for an additional 52 weeks. Mean changes in
      plasma glucose, lipids, and weight were evaluated. Regression and subgroup
      analyses were used to identify relationships between metabolic measures and
      demographic, clinical, and electrophysiological parameters. RESULTS: Duloxetine
      treatment resulted in modest increases in fasting plasma glucose in short- and
      long-term studies (0.50 and 0.67 mmol/l, respectively). A1C did not increase in
      placebo-controlled studies; however, a greater increase was seen relative to
      routine care in long-term studies (0.52 vs. 0.19%). Short-term duloxetine
      treatment resulted in mean weight loss (-1.03 kg; P < 0.001 vs. placebo), whereas
      slight, nonsignificant weight gain was seen in both duloxetine and routine care
      groups with longer treatment. Between-group differences were seen for some lipid
      parameters, but these changes were generally small. Metabolic changes did not
      appear to impact improvement in pain severity seen with duloxetine, and nerve
      conduction was also not significantly impacted by treatment. CONCLUSIONS:
      Duloxetine treatment was associated with modest changes in glycemia in patients
      with DPNP. Other metabolic changes were limited and of uncertain significance.
      These changes did not impact the significant improvement in pain observed with
      duloxetine treatment.

PMID- 17192329
TI  - Problem solving and diabetes self-management: investigation in a large,
      multiracial sample.
AB  - OBJECTIVE: Problem solving is a core aspect of effective diabetes and chronic
      illness self-management, yet there are relatively few objective evaluations of
      problem-solving skills, especially in large, multiracial samples. RESEARCH DESIGN
      AND METHODS: A multiracial sample of 506 adults who have type 2 diabetes were
      assessed on a variety of patient characteristics, self-management behaviors, and
      biological and psychosocial measures. They also completed the Diabetes Problem
      Solving Interview (DPSI). RESULTS: DPSI scores revealed significant variability
      across patients in problem-solving skill and were related to a number of comorbid
      conditions and complications but not to several other demographic factors,
      including race/ethnicity. Problem solving was also related to self-management
      behaviors (eating and exercise patterns), biological variables (A1C and lipids),
      and psychosocial measures (Diabetes Distress Scale) in multivariable analyses
      controlling for a variety of potential confounding factors. CONCLUSIONS: Diabetes
      problem solving, as measured by the DPSI, is an important patient skill related
      to several key diabetes management variables that appears applicable across
      racial and ethnic groups. Future research is needed to identify the generality
      versus specificity of diabetes problem solving and practical interventions to
      enhance problem-solving skills.

PMID- 17192330
TI  - Increasing the accuracy of oral glucose tolerance testing and extending its
      application to individuals with normal glucose tolerance for the prediction of
      type 1 diabetes: the Diabetes Prevention Trial-Type 1.
AB  - OBJECTIVE: We assessed the extent to which both standard and alternative indexes
      from 2-h oral glucose tolerance testing predict type 1 diabetes and whether oral
      glucose tolerance tests (OGTTs) predict type 1 diabetes in individuals with
      normal glucose tolerance. RESEARCH DESIGN AND METHODS: The prediction of type 1
      diabetes from baseline OGTTs was studied in 704 Diabetes Prevention Trial-Type 1
      participants (islet-cell autoantibody [ICA]-positive relatives of type 1 diabetic
      patients). The maximum follow-up was 7.4 years. Analyses utilized receiver
      operator curves (ROCs), proportional hazards models, and survival curves.
      RESULTS: ROC areas under the curve (ROCAUCs) for both the AUC glucose (0.73 +/-
      0.02) and an OGTT prediction index (0.78 +/- 0.02) were higher (P < 0.001) than
      those for the fasting (0.53 +/- 0.02) and 2-h glucose (0.66 +/- 0.02). ROCAUCs
      for the 60- and 90-min glucose (0.71 +/- 0.02 and 0.72 +/- 0.02, respectively)
      were also higher (P < 0.01) than those for the fasting and 2-h glucose. Among
      individuals with normal glucose tolerance, OGTTs were highly predictive, with 4th
      versus 1st quartile hazard ratios for the 2-h glucose, AUC glucose, and OGTT
      prediction index ranging from 3.77 to 5.30 (P < 0.001 for all). CONCLUSIONS:
      Certain alternative OGTT indexes appear to better predict type 1 diabetes than
      standard OGTT indexes in ICA-positive relatives of type 1 diabetic patients.
      Moreover, even among those with normal glucose tolerance, OGTTs are strongly
      predictive. This suggests that subtle metabolic abnormalities are present several
      years before the diagnosis of type 1 diabetes.

PMID- 17192331
TI  - Impact of a managed-Medicare physical activity benefit on health care utilization
      and costs in older adults with diabetes.
AB  - OBJECTIVE: The purpose of this article was to determine the effects of a managed
      Medicare physical activity benefit on health care utilization and costs among
      older adults with diabetes. RESEARCH DESIGN AND METHODS: This retrospective
      cohort study used administrative and claims data for 527 patients from a diabetes
      registry of a staff model HMO. Participants (n = 163) were enrolled in the HMO
      for at least 1 year before joining the Enhanced Fitness Program (EFP), a
      community-based physical activity program for which the HMO pays for each EFP
      class attended. Control subjects were matched to participants according to the
      index date of EFP enrollment (n = 364). Multivariate regression models were used
      to determine 12-month postindex differences in health care use and costs between
      participants and control subjects while adjusting for age, sex, chronic disease
      burden, EFP attendance, prevention score, heart registry, and respective baseline
      use and costs. RESULTS: Participants and control subjects were similar at
      baseline with respect to age (75 +/- 5.5 years), A1C levels (7.4 +/- 1.4%),
      chronic disease burden, prevention score, and health care use and costs. After
      exposure to the program, there was a trend toward lower hospital admissions in
      EFP participants compared with control subjects (13.5 vs. 20.9%, P = 0.08),
      whereas total health care costs were not different (P = 0.39). EFP participants
      who attended > or = 1 exercise session/week on average had approximately 41% less
      total health care costs compared with those attending <1 session/week (P = 0.03)
      and with control subjects (P = 0.02). CONCLUSIONS: Although elective
      participation in a community-based physical activity benefit at any level was not
      associated with lower inpatient or total health care costs, greater participation
      in the program may lower health care costs. These findings warrant additional
      investigations to determine whether policies to offer and promote a community
      based physical activity benefit in older adults with diabetes can reduce health
      care costs.

PMID- 17192332
TI  - Lack of effect of guideline changes on hypertension control for patients with
      diabetes in the U.S., 1995-2005.
AB  - OBJECTIVE: To study the effect of new Joint National Committee on Prevention,
      Detection, Evaluation, and Treatment of High Blood Pressure (JNC) guidelines on
      hypertension control for patients with diabetes in the U.S. using patients
      without diabetes as the control group for the time trend. RESEARCH DESIGN AND
      METHODS: The JNC VI and VII guidelines, published in 1997 and 2003, set more
      aggressive goal blood pressure for patients with diabetes. Data from the National
      Disease and Therapeutic Index, a nationally representative survey of outpatient
      visits in the U.S., was used to compare the difference in hypertension control
      (blood pressure <140/90 mmHg) between diabetic and nondiabetic visits during 1995
      2005. RESULTS: Hypertension control improved for both diabetic and nondiabetic
      visits in the study period. Compared with nondiabetic visits, there was no change
      in hypertension control for diabetic visits before 2001 and an approximately 4%
      increase afterward (P < 0.001). CONCLUSIONS: The publication of new JNC
      guidelines did not result in substantially better hypertension control for
      patients with diabetes in the U.S.

PMID- 17192333
TI  - Adiposity compared with physical inactivity and risk of type 2 diabetes in women.
AB  - OBJECTIVE: The relative contribution of adiposity and physical inactivity to the
      risk of developing type 2 diabetes remains controversial. RESEARCH DESIGN AND
      METHODS: We prospectively examined the individual and joint association of
      obesity and physical activity with the development of type 2 diabetes in 68,907
      female nurses who had no history of diabetes, cardiovascular disease, or cancer
      at baseline. Adiposity was measured by BMI and waist circumference. Physical
      activity was assessed through average hours of moderate or vigorous exercise and
      computation of an MET score. RESULTS: We documented 4,030 incident cases of type
      2 diabetes during 16 years of follow-up (from 1986 to 2002). In a multivariate
      model including age, smoking, and other diabetes risk factors, risk of type 2
      diabetes increased progressively with increasing BMI (P < 0.001) and waist
      circumference (P < 0.001) and with decreasing physical activity levels (P <
      0.001). In joint analyses of BMI and physical activity, using women who had a
      healthy weight (BMI < 25 kg/m(2)) and were physically active (exercise > or =
      21.8 MET h/week) as the reference group, the relative risks of type 2 diabetes
      were 16.75 (95% CI 13.99-20.04) for women who were obese (BMI > or = 30 kg/m(2))
      and inactive (exercise < 2.1 MET h/week), 10.74 (8.74-13.18) for women who were
      active but obese, and 2.08 (1.66-2.61) for women who were lean but inactive. In
      combined analyses of waist circumference and physical activity, both variables
      were significant predictors of type 2 diabetes, but the association for waist
      circumference was substantially stronger than that for physical inactivity.
      CONCLUSIONS: Obesity and physical inactivity independently contribute to the
      development of type 2 diabetes; however, the magnitude of risk contributed by
      obesity is much greater than that imparted by lack of physical activity.

PMID- 17192334
TI  - The accuracy of the FreeStyle Navigator continuous glucose monitoring system in
      children with type 1 diabetes.
AB  - OBJECTIVE: To evaluate the accuracy and precision of the FreeStyle Navigator
      continuous glucose monitoring system in children with type 1 diabetes. RESEARCH
      DESIGN AND METHODS: In 30 children with type 1 diabetes (mean age 11.2 +/- 4.1
      years), the Navigator glucose values were compared with reference serum glucose
      values of blood samples obtained in an inpatient clinical research center and
      measured in a central laboratory using a hexokinase enzymatic method and in an
      outpatient setting with a FreeStyle meter. Median absolute difference (AD) and
      median relative absolute difference (RAD) were computed for sensor-reference and
      sensor-sensor pairs. RESULTS: The median AD and RAD were 17 mg/dl and 12%,
      respectively, for 1,811 inpatient sensor-reference pairs and 20 mg/dl and 14%,
      respectively, for 8,639 outpatient pairs. The median RAD between two simultaneous
      Navigator measurements (n = 1,971) was 13%. Ninety-one percent of sensors in the
      inpatient setting and 81% of sensors in the outpatient setting had a median RAD <
      or = 20%. CONCLUSIONS: The Navigator's accuracy does not yet approach the
      accuracy of current-generation home glucose meters, but it is sufficient to
      believe that the device has the potential to be an important adjunct to treatment
      of youth with type 1 diabetes.

PMID- 17192335
TI  - Development and validation of stroke risk equation for Hong Kong Chinese patients
      with type 2 diabetes: the Hong Kong Diabetes Registry.
AB  - OBJECTIVE: We sought to develop stroke risk equations for Chinese patients with
      type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: A total of 7,209 Hong
      Kong Chinese type 2 diabetic patients without a history of stroke at baseline
      were analyzed. The data were randomly and evenly divided into the training
      subsample and the test subsample. In the training subsample, stepwise Cox models
      were used to develop the risk equation. Validation of the U.K. Prospective
      Diabetes Study (UKPDS) stroke risk engine and the current stroke equation was
      performed in the test dataset. The life-table method was used to check
      calibration, and the area under the receiver operating characteristic curve
      (aROC) was used to check discrimination. RESULTS: A total of 372 patients
      developed incident stroke during a median of 5.37 years (interquartile range 2.88
      7.78) of follow-up. Age, A1C, spot urine albumin-to-creatinine ratio (ACR), and
      history of coronary heart disease (CHD) were independent predictors. The
      performance of the UKPDS stroke engine was suboptimal in our cohort. The newly
      developed risk equation defined by these four predictors had adequate performance
      in the test subsample. The predicted stroke-free probability by the current
      equation was within the 95% CI of the observed probability. The aROC was 0.77 for
      predicting stroke within 5 years. The risk score was computed as follows: 0.0634
      x age (years) + 0.0897 x A1C + 0.5314 x log(10) (ACR) (mg/mmol) + 0.5636 x
      history of CHD (1 if yes). The 5-year stroke probability can be calculated by: 1 
      0.9707(EXP (Risk Score - 4.5674)). CONCLUSIONS: Although the risk equation
      performed reasonably well in Chinese type 2 diabetic patients, external
      validation is required in other populations.

PMID- 17192336
TI  - C-Peptide replacement therapy and sensory nerve function in type 1 diabetic
      neuropathy.
AB  - OBJECTIVE: C-peptide replacement in animals results in amelioration of diabetes
      induced functional and structural abnormalities in peripheral nerves. The present
      study was undertaken to examine whether C-peptide administration to patients with
      type 1 diabetes and peripheral neuropathy improves sensory nerve function.
      RESEARCH DESIGN AND METHODS: This was an exploratory, double-blinded, randomized,
      and placebo-controlled study with three study groups that was carried out at five
      centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided
      into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6
      months. Neurological examination and neurophysiological measurements were
      performed before and after 6 months of treatment with C-peptide or placebo.
      RESULTS: The age of the 139 patients who completed the protocol was 44.2 +/- 0.6
      (mean +/- SE) years and their duration of diabetes was 30.6 +/- 0.8 years.
      Clinical neurological impairment (NIA) (score >7 points) of the lower extremities
      was present in 86% of the patients at baseline. Sensory nerve conduction velocity
      (SCV) was 2.6 +/- 0.08 SD below body height-corrected normal values at baseline
      and improved similarly within the two C-peptide groups (P < 0.007). The number of
      patients responding with a SCV peak potential improvement >1.0 m/s was greater in
      C-peptide-treated patients than in those receiving placebo (P < 0.03). In the
      least severely affected patients (SCV < 2.5 SD below normal at baseline, n = 70)
      SCV improved by 1.0 m/s (P < 0.014 vs. placebo). NIA score and vibration
      perception both improved within the C-peptide-treated groups (P < 0.011 and P <
      0.002). A1C levels (7.6 +/- 0.1% at baseline) decreased slightly but similarly in
      C-peptide-and placebo-treated patients during the study. CONCLUSIONS: C-peptide
      treatment for 6 months improves sensory nerve function in early-stage type 1
      diabetic neuropathy.

PMID- 17192337
TI  - Autonomic nerve testing predicts the development of complications: a 12-year
      follow-up study.
AB  - OBJECTIVE: Cardiac autonomic nerve tests have predicted increased mortality in
      adults with diabetes, predominantly due to nephropathy, cardiac disease, and
      hypoglycemia. The significance of subclinical autonomic nerve test abnormalities
      has not been systematically studied in adolescents. We aimed to reassess an
      adolescent cohort, whose autonomic nervous system had been tested 12 years
      earlier by both pupillometry and cardiovascular tests. RESEARCH DESIGN AND
      METHODS: From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were
      assessed for autonomic neuropathy (median age 14.7 years [interquartile range
      13.0-16.8], duration of diabetes 6.3 years [4.0-9.6], and A1C 8.3% [7.5-9.4]).
      Between 2003 and 2005, contact was made with 59% of the original group.
      Individual assessment 12 years later included completion of a validated
      hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to
      creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of
      reports from external doctors (n = 35). RESULTS: At baseline, there was no
      difference in age, duration of diabetes, or complications between those who
      participated in the follow-up phase (n = 137) and those who did not participate
      (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs.
      8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years
      of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32
      (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no
      microalbuminuria. Small pupil size at baseline was independently associated with
      the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32-14.42], P =
      0.016) and retinopathy (4.83 [1.3-17.98], P = 0.019) but not with the development
      of hypoglycemia unawareness. There was no association with baseline
      cardiovascular tests and the development of complications 12 years later.
      CONCLUSIONS: In this study, we found an association between baseline pupillometry
      tests and the presence of microalbuminuria and retinopathy at 12 years of follow
      up. This suggests that pupillometry abnormalities may be early indicators of
      patients who are at high risk of future microvascular disease.

PMID- 17192338
TI  - Cortisol secretion in patients with type 2 diabetes: relationship with chronic
      complications.
AB  - OBJECTIVE: The presence of an enhanced cortisol secretion in patients with type 2
      diabetes is debated. In type 2 diabetic subjects, cortisol secretion was found to
      be associated with the complications and metabolic control of diabetes. We
      evaluated cortisol secretion in 170 type 2 diabetic subjects and in 71 sex-, age
      , and BMI-matched nondiabetic subjects. RESEARCH DESIGN AND METHODS: In all
      subjects, we evaluated ACTH at 8:00 a.m. in basal conditions and serum cortisol
      levels at 12:00 p.m. (F24) and at 9:00 a.m. after a 1-mg overnight dexamethasone
      suppression test and 24-h urinary free cortisol (UFC). In diabetic patients, we
      evaluated the presence of chronic complications (incipient nephropathy,
      asymptomatic neuropathy, background retinopathy, and silent macroangiopathy).
      Patients were subdivided according to the absence (group 1, n = 53) or presence
      (group 2, n = 117) of diabetes complications. RESULTS: In group 2, UFC (125.2 +/-
      4.6 nmol/24 h) and F24 (120.6 +/- 4.1 nmol/l) were higher than in group 1 (109.2
      +/- 6.8 nmol/24 h, P = 0.057, and 99.7 +/- 6.1 nmol/l, P = 0.005, respectively)
      and in nondiabetic patients (101.7 +/- 5.9 nmol/24 h, P = 0.002, and 100.3 +/-
      5.3 nmol/l, P = 0.003, respectively). In diabetic patients, the number of
      complications was associated with F24 (R = 0.345; P < 0.0001) and diabetes
      duration (R = 0.39; P < 0.0001). Logistic regression analysis showed that the
      presence of diabetes complications was significantly associated with F24, sex,
      duration of diabetes, and glycated hemoglobin. CONCLUSIONS: In type 2 diabetic
      subjects, hypothalamic-pituitary-adrenal activity is enhanced in patients with
      diabetes complications and the degree of cortisol secretion is related to the
      presence and number of diabetes complications.

PMID- 17192339
TI  - Muscle and liver insulin resistance indexes derived from the oral glucose
      tolerance test.
AB  - OBJECTIVE: To derive indexes for muscle and hepatic insulin sensitivity from the
      measurement of plasma glucose and insulin concentrations during an oral glucose
      tolerance test (OGTT). RESEARCH DESIGN AND METHODS: A total of 155 subjects of
      Mexican-American origin (58 male and 97 female, aged 18-70 years, BMI 20-65
      kg/m(2)) with normal glucose tolerance (n = 100) or impaired glucose tolerance (n
      = 55) were studied. Each subject received a 75-g OGTT and a euglycemic insulin
      clamp in combination with tritiated glucose. The OGTT-derived indexes of muscle
      and hepatic insulin sensitivity were compared with hepatic and muscle insulin
      sensitivity, which was directly measured with the insulin clamp, by correlation
      analysis. RESULTS: The product of total area under curve (AUC) for glucose and
      insulin during the first 30 min of the OGTT (glucose(0-30)[AUC] x insulin(0
      30)[AUC]) strongly correlated with the hepatic insulin resistance index (fasting
      plasma insulin x basal endogenous glucose production) (r = 0.64, P < 0.0001). The
      rate of decay of plasma glucose concentration from its peak value to its nadir
      during the OGTT divided by the mean plasma insulin concentration (dG/dt / I)
      strongly correlated with muscle insulin sensitivity measured with the insulin
      clamp (P = 0.78, P < 0.0001). CONCLUSIONS: Novel estimates for hepatic and muscle
      insulin resistance from OGTT data are presented for quantitation of insulin
      sensitivity in nondiabetic subjects.

PMID- 17192340
TI  - Signs of beta-cell autoimmunity in nondiabetic schoolchildren: a comparison
      between Russian Karelia with a low incidence of type 1 diabetes and Finland with
      a high incidence rate.
AB  - OBJECTIVE: We sought to study the prevalence of autoantibodies to various islet
      cell antigens in the background population of two neighboring countries with a
      sixfold difference in the incidence of type 1 diabetes. RESEARCH DESIGN AND
      METHODS: Serum samples were obtained from 3,652 nondiabetic schoolchildren in
      Finland and from 1,988 schoolchildren in the adjacent Karelian Republic of
      Russia. The Karelian children were divided into three groups (Finns/Karelians,
      Russians, and others) based on the ethnic background of their mother. The samples
      were analyzed for islet cell antibodies (ICAs), insulin autoantibodies (IAAs),
      GAD antibodies (GADAs), and the tyrosine phosphatase-like insulinoma antigen 2
      (IA-2A) protein and HLA class II genotypes. RESULTS: The frequency of ICAs, IAAs,
      and GADAs did not differ significantly between the Karelian (3.5, 0.6, and 0.9%,
      respectively) and Finnish children (2.8, 0.9, and 0.5%, respectively). Similarly,
      the frequency of multiple (> or = 2) autoantibodies was similar in both countries
      (0.5 vs. 0.6%). The frequency of IA-2A was, however, four times higher in Finland
      (0.6 vs. 0.15% in Russian Karelia; P = 0.03). There were no significant
      differences in autoantibody prevalence among the three ethnic groups in Russian
      Karelia. There was a falling frequency of GADAs and of positivity for multiple
      autoantibodies along with decreasing HLA-conferred disease susceptibility among
      the Finnish schoolchildren. CONCLUSIONS: These data indicate that beta-cell
      autoimmunity among schoolchildren is as frequent in Russian Karelia as in
      Finland, although the incidence of clinical type 1 diabetes is six times higher
      in Finland. However, in contrast to this general trend, IA-2As were more common
      in Finland. Since IA-2As usually appear late in the preclinical process, this
      suggests that progressive beta-cell autoimmunity is more rare in Russian Karelia.

PMID- 17192341
TI  - Heme iron from diet as a risk factor for coronary heart disease in women with
      type 2 diabetes.
AB  - OBJECTIVE: Diabetes-related metabolic abnormality may aggravate the adverse
      effects of iron overload on cardiovascular health. However, little is known about
      whether iron consumption affects coronary heart disease (CHD) risk in diabetes.
      RESEARCH DESIGN AND METHODS: We prospectively assessed the associations of long
      term intakes of dietary iron and red meat with CHD risk among 6,161 women who
      reported a diagnosis of type 2 diabetes. RESULTS: During 54,455 person-years of
      follow-up from 1980 through 2000, we documented 550 incident cases of CHD. After
      adjustment for age and BMI, high intakes of both heme iron and red meat were
      associated with a significantly increased risk of fatal CHD (P for trend = 0.003
      and 0.018), coronary revascularization (P for trend = 0.02 and 0.06), and total
      CHD (P for trend = 0.0009 and 0.007). Women with the highest intake of heme iron
      had 50% (6-94%) increased risk of total CHD compared with those with the lowest
      intake. Further adjustment for other lifestyle and dietary factors did not
      appreciably change the associations. The positive association between heme iron
      and red meat intakes and CHD was more evident among postmenopausal women compared
      with premenopausal women. CONCLUSIONS: Our data indicate that higher consumption
      of heme iron and red meat may increase CHD risk among women with type 2 diabetes.

PMID- 17192342
TI  - Skin autofluorescence is a strong predictor of cardiac mortality in diabetes.
AB  - OBJECTIVE: Advanced glycation end products (AGEs) are biomarkers of metabolic
      stress and are thought to contribute to the increase of coronary heart disease
      (CHD) in diabetes. Tissue autofluorescence is related to the accumulation of
      AGEs. The aim of the present study was to evaluate the relationship between skin
      autofluorescence and metabolic burden (hyperglycemia and hyperlipidemia) and its
      relationship with CHD and mortality. RESEARCH DESIGN AND METHODS: Skin
      autofluorescence was measured noninvasively with an autofluorescence reader in 48
      type 1 and 69 type 2 diabetic patients and 43 control subjects. The presence of
      CHD was observed at baseline and mortality during a follow-up period of 5 years.
      RESULTS: Autofluorescence correlated with mean A1C, triglycerides, and LDL.
      Autofluorescence values further increased with age, microalbuminuria, dialysis
      treatment, and diabetes duration. Autofluorescence was strongly related to the
      presence of CHD (odds ratio 7.9) and predicted mortality (3.0). Multivariate
      analysis showed that autofluorescence was more strongly associated with CHD and
      mortality compared with A1C, triglycerides, and LDL. CONCLUSIONS: Skin
      autofluorescence is strongly related to cumulative metabolic burden. Skin
      autofluorescence seems strongly associated with cardiac mortality and may provide
      important clinical information for risk assessment.

PMID- 17192343
TI  - Prevalence of metabolic syndrome in HIV-infected patients receiving highly active
      antiretroviral therapy using International Diabetes Foundation and Adult
      Treatment Panel III criteria: associations with insulin resistance, disturbed
      body fat compartmentalization, elevated C-reactive protein, and [corrected]
      hypoadiponectinemia.
AB  - OBJECTIVE: Metabolic syndrome is a cluster of risk factors for cardiovascular
      disease and type 2 diabetes. Definitions exist to identify those "at risk."
      Treatment of HIV infection with highly active antiretroviral therapy can induce
      severe metabolic complications including lipodystrophy, dyslipidemia, and insulin
      resistance. The purpose of this study was to report the prevalence of metabolic
      syndrome in HIV-infected patients and compare insulin resistance and total body,
      limb, and visceral fat and adipokines in those with and without metabolic
      syndrome. RESEARCH DESIGN AND METHODS: This was an international cross-sectional
      study of a well-characterized cohort of 788 HIV-infected adults recruited at 32
      centers. Metabolic syndrome prevalence was examined using International Diabetes
      Federation (IDF) and U.S. National Cholesterol Education Program Adult Treatment
      Panel III (ATPIII) criteria, relative to body composition (whole-body dual-energy
      X-ray absorptiometry and abdominal computed tomography), lipids, glycemic
      parameters, insulin resistance, leptin, adiponectin, and C-reactive protein
      (CRP). RESULTS: The prevalence of metabolic syndrome was 14% (n = 114; 83 men) by
      IDF criteria and 18% (n = 139; 118 men) by ATPIII criteria; the concordance was
      significant but only moderate (kappa = 0.46, P < 0.0001). Many patients (49%) had
      at least two features of metabolic syndrome but were not classified as having
      metabolic syndrome as their waist circumferences or waist-to-hip ratios were in
      the non-metabolic syndrome range. Metabolic syndrome was more common in those
      currently receiving protease inhibitors (P = 0.04). Type 2 diabetes prevalence
      was five- to ninefold higher in those with metabolic syndrome. With IDF criteria,
      subjects with metabolic syndrome showed disturbances in inflammation and
      adipokines: they had higher CRP (5.5 +/- 7.0 vs. 3.9 +/- 6.0 mg/l, P < 0.003) and
      leptin (9 +/- 9 vs. 4 +/- 6 ng/ml, P < 0.0001) and lower adiponectin (12 +/- 8
      vs. 15 +/- 10 microg/ml, P < 0.0001) levels. By ATPIII criteria, those with
      metabolic syndrome had higher leptin (6 +/- 8 ng/ml, P = 0.006) and lower
      adiponectin (15 +/- 10 vs. 18 +/- 8 microg/ml, P < 0.0001) levels. CONCLUSIONS:
      Metabolic syndrome prevalence in HIV-positive adults was lower than that reported
      for the general population. Metabolic syndrome was associated with a
      substantially increased prevalence of type 2 diabetes in this specific cohort.
      Many subjects without metabolic syndrome had at least two metabolic syndrome
      components (particularly elevated lipid levels) but did not meet waist
      circumference or waist-to-hip ratio cutoff metabolic syndrome criteria in this
      group with high rates of body fat partitioning disturbances.

PMID- 17192344
TI  - Minimum waist and visceral fat values for identifying Japanese Americans at risk
      for the metabolic syndrome.
AB  - OBJECTIVE: Japanese American is an ethnic group with a high risk for type 2
      diabetes, which is linked to the metabolic syndrome. Central adiposity is
      considered to play a key role in the metabolic syndrome. Not known are the
      optimal cut point values for central and visceral adiposity to identify Japanese
      Americans at risk for the metabolic syndrome. RESEARCH DESIGN AND METHODS: Study
      subjects included 639 Japanese Americans. The nonadipose variables of the
      metabolic syndrome were defined using modified International Diabetes Federation
      criteria, and the accuracy of identifying at least two of these by intra
      abdominal fat area (IAFA) as measured by computed tomography and waist
      circumference was cross-sectionally assessed using area under receiver operating
      characteristic (ROC) curves. The values for IAFA and waist circumference that
      resulted in maximizing the Youden index were defined as "optimal." RESULTS: The
      area under the ROC curve for IAFA exceeded that for waist circumference (men
      0.787 vs. 0.686; women 0.792 vs. 0.721). For women, the optimal cut points for
      IAFA and waist circumference were 51.5 cm(2) and 80.8 cm (age < or = 56 years)
      and 86.3 cm(2) and 89.0 cm (age > 56 years). For men, the optimal cut points for
      IAFA and waist circumference were 88.6 cm(2) and 90.0 cm (age < or = 57 years)
      and 96.1 cm(2) and 87.1 cm (age > 57 years). CONCLUSIONS: These results argue
      that current Japanese waist circumference cut points for the metabolic syndrome
      need to be revised. Moreover, the waist circumference and IAFA cut points should
      be age specific, especially in women. Appropriate waist circumference cut points
      are from 80 to 90 cm in women and from 87 to 90 cm in men.

PMID- 17192345
TI  - Lifestyle interventions are cost-effective in people with different levels of
      diabetes risk: results from a modeling study.
AB  - OBJECTIVE: In the current study we explore the long-term health benefits and cost
      effectiveness of both a community-based lifestyle program for the general
      population (community intervention) and an intensive lifestyle intervention for
      obese adults, implemented in a health care setting (health care intervention).
      RESEARCH DESIGN AND METHODS: Short-term intervention effects on BMI and physical
      activity were estimated from the international literature. The National Institute
      for Public Health and the Environment Chronic Diseases Model was used to project
      lifetime health effects and effects on health care costs for minimum and maximum
      estimates of short-term intervention effects. Cost-effectiveness was evaluated
      from a health care perspective and included intervention costs and related and
      unrelated medical costs. Effects and costs were discounted at 1.5 and 4.0%
      annually. RESULTS: One new case of diabetes per 20 years was prevented for every
      7-30 participants in the health care intervention and for every 300-1,500 adults
      in the community intervention. Intervention costs needed to prevent one new case
      of diabetes (per 20 years) were lower for the community intervention (2,000-9,000
      euros) than for the health care intervention (5,000-21,000 euros). The cost
      effectiveness ratios were 3,100-3,900 euros per quality-adjusted life-year (QALY)
      for the community intervention and 3,900-5,500 euros per QALY for the health care
      intervention. CONCLUSIONS: Health care interventions for high-risk groups and
      community-based lifestyle interventions targeted to the general population (low
      risk) are both cost-effective ways of curbing the growing burden of diabetes.

PMID- 17192347
TI  - Food intake enhances thromboxane receptor-mediated platelet activation in type 2
      diabetic patients but not in healthy subjects.

PMID- 17192346
TI  - Relative inaccuracy of the A1cNow in children with type 1 diabetes.

PMID- 17192348
TI  - Accuracy of administrative coding for type 2 diabetes in children, adolescents,
      and young adults.

PMID- 17192349
TI  - Purified eicosapentaenoic acid reduces small dense LDL, remnant lipoprotein
      particles, and C-reactive protein in metabolic syndrome.

PMID- 17192350
TI  - Transfer to sulphonylurea therapy in adult subjects with permanent neonatal
      diabetes due to KCNJ11-activating [corrected] mutations: evidence for improvement
      in insulin sensitivity.

PMID- 17192351
TI  - Coronary vasomotor function is abnormal in first-degree relatives of patients
      with type 2 diabetes.

PMID- 17192352
TI  - Increased risk of type 2 diabetes from a family history of coronary heart disease
      and type 2 diabetes.

PMID- 17192353
TI  - Acute insulin response and beta-cell compensation in normal subjects treated with
      olanzapine or risperidone for 2 weeks.

PMID- 17192354
TI  - Serum interleukin-18 levels are increased and closely associated with various
      soluble adhesion molecule levels in type 1 diabetic patients.

PMID- 17192355
TI  - Primary prevention of cardiovascular diseases in people with diabetes mellitus: a
      scientific statement from the American Heart Association and the American
      Diabetes Association.
AB  - The American Heart Association (AHA) and the American Diabetes Association (ADA)
      have each published guidelines for cardiovascular disease prevention: the ADA has
      issued separate recommendations for each of the cardiovascular risk factors in
      patients with diabetes, and the AHA has shaped primary and secondary guidelines
      that extend to patients with diabetes. This statement will attempt to harmonize
      the recommendations of both organizations where possible but will recognize areas
      in which AHA and ADA recommendations differ.

PMID- 17192356
TI  - Generic drugs.

PMID- 17192357
TI  - Achieving glycemic goals in type 2 diabetes.

PMID- 17192358
TI  - Use of tobramycin-impregnated calcium sulphate pellets in addition to oral
      antibiotics: an alternative treatment to minor amputation in a case of diabetic
      foot osteomyelitis.

PMID- 17192359
TI  - Effects of angiotensin II type 1 receptor blockade on beta-cell function in
      humans.

PMID- 17192360
TI  - Acute renal failure following oral sodium phosphate bowel preparation in
      diabetes.

PMID- 17192361
TI  - Is self-monitoring of blood glucose appropriate for all type 2 diabetic patients?
      The Fremantle Diabetes Study.

PMID- 17192363
TI  - The effect of glucose variability on the risk of microvascular complications in
      type 1 diabetes.

PMID- 17192364
TI  - The effect of glucose variability on the risk of microvascular complications in
      type 1 diabetes.

PMID- 17192365
TI  - The effect of glucose variability on the risk of microvascular complications in
      type 1 diabetes.

PMID- 17192366
TI  - The effect of glucose variability on the risk of microvascular complications in
      type 1 diabetes.

PMID- 17192370
TI  - Impact of glycemic control on survival of diabetic patients on chronic regular
      hemodialysis: a 7-year observational study.

PMID- 17192372
TI  - Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the
      initiation and adjustment of therapy: a consensus statement from the American
      Diabetes Association and the European Association for the Study of Diabetes.

PMID- 17192371
TI  - Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the
      initiation and adjustment of therapy: a consensus statement from the American
      Diabetes Association and the European Association for the Study of Diabetes.

PMID- 17192373
TI  - Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the
      initiation and adjustment of therapy: a consensus statement from the American
      Diabetes Association and the European Association for the Study of Diabetes.

PMID- 17192374
TI  - Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the
      initiation and adjustment of therapy: a consensus statement from the American
      Diabetes Association and the European Association for the Study of Diabetes.

PMID- 17192377
TI  - Standards of medical care in diabetes--2007.

PMID- 17192378
TI  - Diagnosis and classification of diabetes mellitus.

PMID- 17192380
TI  - Diabetes care in the school and day care setting.

PMID- 17192379
TI  - Nutrition Recommendations and Interventions for Diabetes: a position statement of
      the American Diabetes Association.

PMID- 17192381
TI  - Diabetes care at diabetes camps.

PMID- 17192382
TI  - Diabetes management in correctional institutions.

PMID- 17192383
TI  - Hypoglycemia and employment/licensure.

PMID- 17192384
TI  - Third-party reimbursement for diabetes care, self-management education, and
      supplies.

PMID- 17192388
TI  - National standards for diabetes self-management education.

PMID- 17192389
TI  - K-RasG12D expression induces hyperproliferation and aberrant signaling in primary
      hematopoietic stem/progenitor cells.
AB  - Defining how cancer-associated mutations perturb signaling networks in
      stem/progenitor populations that are integral to tumor formation and maintenance
      is a fundamental problem with biologic and clinical implications. Point mutations
      in RAS genes contribute to many cancers, including myeloid malignancies. We
      investigated the effects of an oncogenic Kras(G12D) allele on phosphorylated
      signaling molecules in primary c-kit(+) lin(-/low) hematopoietic stem/progenitor
      cells. Comparison of wild-type and Kras(G12D) c-kit(+) lin(-/low) cells shows
      that K-Ras(G12D) expression causes hyperproliferation in vivo and results in
      abnormal levels of phosphorylated STAT5, ERK, and S6 under basal and stimulated
      conditions. Whereas Kras(G12D) cells demonstrate hyperactive signaling after
      exposure to granulocyte-macrophage colony-stimulating factor, we unexpectedly
      observe a paradoxical attenuation of ERK and S6 phosphorylation in response to
      stem cell factor. These studies provide direct biochemical evidence that cancer
      stem/progenitor cells remodel signaling networks in response to oncogenic stress
      and demonstrate that multi-parameter flow cytometry can be used to monitor the
      effects of targeted therapeutics in vivo. This strategy has broad implications
      for defining the architecture of signaling networks in primary cancer cells and
      for implementing stem cell-targeted interventions.

PMID- 17192390
TI  - Pre-TCR expression cooperates with TEL-JAK2 to transform immature thymocytes and
      induce T-cell leukemia.
AB  - The TEL-JAK2 gene fusion, which has been identified in human leukemia, encodes a
      chimeric protein endowed with constitutive tyrosine kinase activity. TEL-JAK2
      transgenic expression in the mouse lymphoid lineage results in fatal and rapid T
      cell leukemia/lymphoma. In the present report we show that T-cell leukemic cells
      from EmuSRalpha-TEL-JAK2 transgenic mice present an aberrant CD8(+)
      differentiation phenotype, as determined by the expression of stage-specific cell
      surface markers and lineage-specific genes. TEL-JAK2 transforms immature CD4(
      )CD8(-) double-negative thymocytes, as demonstrated by the development of T-cell
      leukemia with full penetrance in a Rag2-deficient genetic background. This
      disease is similar to the bona fide TEL-JAK2 disease as assessed by phenotypic
      and gene profiling analyses. Pre-TCR signaling synergizes with TEL-JAK2 to
      transform immature thymocytes and initiate leukemogenesis as shown by (1) the
      delayed leukemia onset in Rag2-, CD3epsilon- and pTalpha-deficient mice, (2) the
      occurrence of recurrent chromosomal alterations in pre-TCR-deficient leukemia,
      and (3) the correction of delayed leukemia onset in Rag2-deficient TEL-JAK2 mice
      by an H-Y TCRalphabeta transgene that mimics pre-TCR signaling. Although not
      affecting leukemia incidence and mouse survival, TCRalphabeta expression was
      shown to facilitate leukemic cell expansion in secondary lymphoid organs.

PMID- 17192393
TI  - RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron
      deficient phenotype with mitochondrial iron overload.
AB  - X-linked sideroblastic anemia with ataxia (XLSA/A) is caused by defects of the
      transporter ABCB7 and is characterized by mitochondrial iron deposition and
      excess of protoporphyrin in erythroid cells. We describe ABCB7 silencing in HeLa
      cells by performing sequential transfections with siRNAs. The phenotype of the
      ABCB7-deficient cells was characterized by a strong reduction in proliferation
      rate that was not rescued by iron supplementation, by evident signs of iron
      deficiency, and by a large approximately 6-fold increase of iron accumulation in
      the mitochondria that was poorly available to mitochondrial ferritin. The cells
      showed an increase of protoporphyrin IX, a higher sensitivity to H(2)O(2)
      toxicity, and a reduced activity of mitochondrial superoxide dismutase 2 (SOD2),
      while the activity of mitochondrial enzymes, such as citrate synthase or
      succinate dehydrogenase, and ATP content were not decreased. In contrast,
      aconitase activity, particularly that of the cytosolic, IRP1 form, was reduced.
      The results support the hypothesis that ABCB7 is involved in the transfer of iron
      from mitochondria to cytosol, and in the maturation of cytosolic Fe/S enzymes. In
      addition, the results indicate that anemia in XLSA/A is caused by the
      accumulation of iron in a form that is not readily usable for heme synthesis.

PMID- 17192391
TI  - Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an
      osteoclast-dependent manner.
AB  - Inhibition of osteoclast (OC) activity has been associated with decreased tumor
      growth in bone in animal models. Increased recognition of factors that promote
      osteoclastic bone resorption in cancer patients led us to investigate whether
      increased OC activation could enhance tumor growth in bone. Granulocyte colony
      stimulating factor (G-CSF) is used to treat chemotherapy-induced neutropenia, but
      is also associated with increased markers of OC activity and decreased bone
      mineral density (BMD). We used G-CSF as a tool to investigate the impact of
      increased OC activity on tumor growth in 2 murine osteolytic tumor models. An 8
      day course of G-CSF alone (without chemotherapy) significantly decreased BMD and
      increased OC perimeter along bone in mice. Mice administered G-CSF alone
      demonstrated significantly increased tumor growth in bone as quantitated by in
      vivo bioluminescence imaging and histologic bone marrow tumor analysis. Short
      term administration of AMD3100, a CXCR4 inhibitor that mobilizes neutrophils with
      little effect on bone resorption, did not lead to increased tumor burden.
      However, OC-defective osteoprotegerin transgenic (OPG(Tg)) mice and
      bisphosphonate-treated mice were resistant to the effects of G-CSF administration
      upon bone tumor growth. These data demonstrate a G-CSF-induced stimulation of
      tumor growth in bone that is OC dependent.

PMID- 17192392
TI  - Differential effects of IL-21 and IL-15 on perforin expression, lysosomal
      degranulation, and proliferation in CD8 T cells of patients with human
      immunodeficiency virus-1 (HIV).
AB  - An urgent need exists to devise strategies to augment antiviral immune responses
      in patients with HIV who are virologically well controlled and immunologically
      stable on highly active antiretroviral therapy (HAART). The objective of this
      study was to compare the immunomodulatory effects of the cytokines interleukin
      (IL)-21 with IL-15 on CD8 T cells in patients with HIV RNA of less than 50
      copies/mL and CD4 counts greater than 200 cells/mm.(3) Patient CD8 T cells
      displayed skewed maturation and decreased perforin expression compared with
      healthy controls. Culture of freshly isolated patient peripheral-blood
      mononuclear cells (PBMCs) for 5 hours to 5 days with IL-21 resulted in up
      regulation of perforin in CD8 T cells, including memory and effector subsets and
      virus-specific T cells. IL-21 did not induce T-cell activation or proliferation,
      nor did it augment T-cell receptor (TCR)-induced degranulation. Treatment of
      patient PBMCs with IL-15 resulted in induction of perforin in association with
      lymphocyte proliferation and augmentation of TCR-induced degranulation. Patient
      CD8 T cells were more responsive to cytokine effects than the cells of healthy
      volunteers. We conclude that CD8 T cells of patients with HIV can be modulated by
      IL-21 to increase perforin expression without undergoing overt cellular
      activation. IL-21 could potentially be useful for its perforin-enhancing
      properties in anti-HIV immunotherapy.

PMID- 17192394
TI  - Pathogenic proline mutation in the linker between spectrin repeats: disease
      caused by spectrin unfolding.
AB  - Pathogenic mutations in alpha and beta spectrin result in a variety of syndromes,
      including hereditary elliptocytosis (HE), hereditary pyropoikilocytosis (HPP),
      and hereditary spherocytosis (HS). Although some mutations clearly lie at sites
      of interaction, such as the sites of spectrin alpha-betatetramer formation, a
      surprising number of HE-causing mutations have been identified within linker
      regions between distal spectrin repeats. Here we apply solution structural and
      single molecule methods to the folding and stability of recombinant proteins
      consisting of the first 5 spectrin repeats of alpha-spectrin, comparing normal
      spectrin with a pathogenic linker mutation, Q471P, between repeats R4 and R5.
      Results show that the linker mutation destabilizes a significant fraction of the
      5-repeat construct at 37 degrees C, whereas the WT remains fully folded well
      above body temperature. In WT protein, helical linkers propagate stability from
      one repeat to the next, but the mutation disrupts the stabilizing influence of
      adjacent repeats. The results suggest a molecular mechanism for the high
      frequency of disease caused by proline mutations in spectrin linkers.

PMID- 17192395
TI  - Comparative gene expression profiling of in vitro differentiated megakaryocytes
      and erythroblasts identifies novel activatory and inhibitory platelet membrane
      proteins.
AB  - To identify previously unknown platelet receptors we compared the transcriptomes
      of in vitro differentiated megakaryocytes (MKs) and erythroblasts (EBs). RNA was
      obtained from purified, biologically paired MK and EB cultures and compared using
      cDNA microarrays. Bioinformatical analysis of MK-up-regulated genes identified
      151 transcripts encoding transmembrane domain-containing proteins. Although many
      of these were known platelet genes, a number of previously unidentified or poorly
      characterized transcripts were also detected. Many of these transcripts,
      including G6b, G6f, LRRC32, LAT2, and the G protein-coupled receptor SUCNR1,
      encode proteins with structural features or functions that suggest they may be
      involved in the modulation of platelet function. Immunoblotting on platelets
      confirmed the presence of the encoded proteins, and flow cytometric analysis
      confirmed the expression of G6b, G6f, and LRRC32 on the surface of platelets.
      Through comparative analysis of expression in platelets and other blood cells we
      demonstrated that G6b, G6f, and LRRC32 are restricted to the platelet lineage,
      whereas LAT2 and SUCNR1 were also detected in other blood cells. The
      identification of the succinate receptor SUCNR1 in platelets is of particular
      interest, because physiologically relevant concentrations of succinate were shown
      to potentiate the effect of low doses of a variety of platelet agonists.

PMID- 17192396
TI  - Trough imatinib plasma levels are associated with both cytogenetic and molecular
      responses to standard-dose imatinib in chronic myeloid leukemia.
AB  - Using high-performance liquid chromatography-tandem mass spectrometry, we
      assessed trough imatinib plasma levels in 68 patients with chronic myeloid
      leukemia (CML) who responded or not to standard-dose imatinib, after at least 12
      months' treatment. Mean trough imatinib plasma levels were significantly higher
      in the group with complete cytogenetic response (56 patients) than in the group
      without (12 patients; P = .03) and higher in the group with major molecular
      response (MMR) than in the group without (34 patients [1452 +/- 649 ng/mL] versus
      34 patients [869 +/- 427 ng/mL]; P < .001). Regarding trough imatinib plasma
      levels and their discrimination potential for MMR, the area under receiver
      operating characteristic curve was 0.775, with best sensitivity (77%) and
      specificity (71%) at a plasma threshold of 1002 ng/mL. Therefore, monitoring of
      imatinib plasma levels could be very useful for the management of patients with
      CML or should at least be checked in the case of treatment failure or suboptimal
      response.

PMID- 17192397
TI  - Integrated molecular profiling of SOD2 expression in multiple myeloma.
AB  - Reactive oxygen species are known to be involved in several cellular processes,
      including cell signaling. SOD2 is a key enzyme in the conversion of reactive
      oxygen species and has been implicated in a host of disease states, including
      cancer. Using an integrated, whole-cell approach encompassing epigenetics,
      genomics, and proteomics, we have defined the role of SOD2 in multiple myeloma.
      We show that the SOD2 promoter is methylated in several cell lines and there is a
      correlative decrease in expression. Furthermore, myeloma patient samples have
      decreased SOD2 expression compared with healthy donors. Overexpression of SOD2
      results in decreased proliferation and altered sensitivity to 2-methoxyestradiol
      induced DNA damage and apoptosis. Genomic profiling revealed regulation of 65
      genes, including genes involved in tumorigenesis, and proteomic analysis
      identified activation of the JAK/STAT pathway. Analysis of nearly 400 activated
      transcription factors identified 31 transcription factors with altered DNA
      binding activity, including XBP1, NFAT, forkhead, and GAS binding sites.
      Integration of data from our gestalt molecular analysis has defined a role for
      SOD2 in cellular proliferation, JAK/STAT signaling, and regulation of several
      transcription factors.

PMID- 17192399
TI  - Stimulation of P2 receptors causes release of IL-1beta-loaded microvesicles from
      human dendritic cells.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells that initiate the
      immune response by activating T lymphocytes. DCs express plasma membrane
      receptors for extracellular nucleotides named P2 receptors (P2Rs). Stimulation of
      P2Rs in these cells is known to cause chemotaxis, cytokine release, and cell
      death and to modulate LPS-dependent differentiation. Here we show that
      stimulation of the P2X(7) receptor subtype (P2X(7)R) causes fast microvesicle
      shedding from DC plasma membrane. Vesicle release occurs from both immature and
      mature DCs; however, only vesicles from mature DCs, due to their previous
      exposure to LPS, contain IL-1beta. Microvesicles, whether from immature or mature
      DCs, also contain caspase-1 and -3 and cathepsin D. They also express the P2X(7)R
      in addition to other P2Rs and known markers of immune cells such as major
      histocompatibility complex II (MHC II) and CD39. Activation of the P2X(7)R by
      extracellular ATP causes IL-1beta release from the vesicle lumen. Previous
      studies demonstrated that high extracellular K(+) inhibits IL-1beta processing
      and release; here we show that high ionic strength reduces microvesicle shedding
      when compared with a low ionic strength medium but strongly increases
      microvesicle IL-1beta loading.

PMID- 17192398
TI  - Abcb7, the gene responsible for X-linked sideroblastic anemia with ataxia, is
      essential for hematopoiesis.
AB  - X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare syndromic form of
      inherited sideroblastic anemia associated with spinocerebellar ataxia, and is due
      to mutations in the mitochondrial ATP-binding cassette transporter Abcb7. Here,
      we show that Abcb7 is essential for hematopoiesis and formally demonstrate that
      XLSA/A is due to partial loss of function mutations in Abcb7 that directly or
      indirectly inhibit heme biosynthesis.

PMID- 17192400
TI  - Differential fitness costs of reproduction between the sexes.
AB  - Natural selection does not necessarily favor maximal reproduction because
      reproduction imposes fitness costs, reducing parental survival, and offspring
      quality. Here, we show that parents in a preindustrial population in North
      America incurred fitness costs from reproduction, and women incurred greater
      costs than men. We examined the survivorship and reproductive success (Darwinian
      fitness) of 21,684 couples married between 1860 and 1895 identified in the Utah
      Population Database. We found that increasing number of offspring (parity) and
      rates of reproduction were associated with reduced parental survivorship, and
      significantly more for mothers than fathers. Parental mortality resulted in
      reduced survival and reproduction of offspring, and the mothers' mortality was
      more detrimental to offspring than the fathers'. Increasing family size was
      associated with lower offspring survival, primarily for later-born children,
      indicating a tradeoff between offspring quantity versus quality. Also, we found
      that the costs of reproduction increased with age more for women than men. Our
      findings help to explain some puzzling aspects of human reproductive physiology
      and behavior, including the evolution of menopause and fertility declines
      associated with improvements in women's status (demographic transitions).

PMID- 17192401
TI  - Chemically engineered extracts as an alternative source of bioactive natural
      product-like compounds.
AB  - The access to libraries of molecules with interesting biomolecular properties is
      a limiting step in the drug discovery process. By virtue of a long molecular
      evolution process, natural products are recognized as biologically validated
      starting points in structural space for library development. We introduce here a
      strategy to generate natural product-like libraries. A semisynthetic mixture of
      compounds was produced by diversification of a natural product extract through
      the chemical transformation of common chemical functionalities in natural
      products into chemical functionalities rarely found in nature. The resulting
      mixture showed antifungal activity against Candida albicans, whereas the starting
      extract did not show such activity. Bioguided fractionation led to the isolation
      of a previously undescribed active semisynthetic pyrazole. The result illustrates
      how biological activity can be generated by designed chemical diversification of
      a natural product mixture, and represents the proof of principle of an
      alternative strategy for producing natural product-like libraries from natural
      products libraries.

PMID- 17192402
TI  - Evidence of the existence of the low-density liquid phase in supercooled,
      confined water.
AB  - By confining water in a nanoporous structure so narrow that the liquid could not
      freeze, it is possible to study properties of this previously undescribed system
      well below its homogeneous nucleation temperature TH = 231 K. Using this trick,
      we were able to study, by means of a Fourier transform infrared spectroscopy,
      vibrational spectra (HOH bending and OH-stretching modes) of deeply supercooled
      water in the temperature range 183 < T < 273 K. We observed, upon decreasing
      temperature, the building up of a new population of hydrogen-bonded oscillators
      centered around 3,120 cm(-1), the contribution of which progressively dominates
      the spectra as one enters into the deeply supercooled regime. We determined that
      the fractional weight of this spectral component reaches 50% just at the
      temperature, TL approximately 225 K, where the confined water shows a fragile-to
      strong dynamic cross-over phenomenon [Ito, K., Moynihan, C. T., Angell, C. A.
      (1999) Nature 398:492-494]. Furthermore, the fact that the corresponding OH
      stretching spectral peak position of the low-density-amorphous solid water occurs
      exactly at 3,120 cm(-1) [Sivakumar, T. C., Rice, S. A., Sceats, M. G. (1978) J.
      Chem. Phys. 69:3468-3476.] strongly suggests that these oscillators originate
      from existence of the low-density-liquid phase derived from the occurrence of the
      first-order liquid-liquid (LL) phase transition and the associated LL critical
      point in supercooled water proposed earlier by a computer molecular dynamics
      simulation [Poole, P. H., Sciortino, F., Essmann, U., Stanley, H. E. (1992)
      Nature 360:324-328].

PMID- 17192403
TI  - Two complex, adenovirus-based vaccines that together induce immune responses to
      all four dengue virus serotypes.
AB  - Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and
      even death. Worldwide, approximately 2.5 billion people live in dengue-infested
      regions with about 100 million new cases each year, although many of these
      infections are believed to be silent. There are four antigenically distinct
      serotypes of dengue virus; thus, immunity from one serotype will not cross
      protect from infection with the other three. The difficulties that hamper vaccine
      development include requirements of the natural conformation of the envelope
      glycoprotein to induce neutralizing immune responses and the necessity of
      presenting antigens of all four serotypes. Currently, the only way to meet these
      requirements is to use a mixture of four serotypes of live attenuated dengue
      viruses, but safety remains a major problem. In this study, we have developed the
      basis for a tetravalent dengue vaccine using a novel complex adenovirus platform
      that is capable of expressing multiple antigens de novo. This dengue vaccine is
      constructed as a pair of vectors that each expresses the premembrane and envelope
      genes of two different dengue virus serotypes. Upon vaccination, the vaccine
      expressed high levels of the dengue virus antigens in cells to mimic a natural
      infection and induced both humoral and cellular immune responses against multiple
      serotypes of dengue virus in an animal model. Further analyses show the humoral
      responses were indeed neutralizing against all four serotypes. Our studies
      demonstrate the concept of mimicking infections to induce immune responses by
      synthesizing dengue virus membrane antigens de novo and the feasibility of
      developing an effective tetravalent dengue vaccine by vector-mediated expression
      of glycoproteins of the four serotypes.

PMID- 17192404
TI  - Differential functions of the Aurora-B and Aurora-C kinases in mammalian
      spermatogenesis.
AB  - The Aurora kinases are cell cycle-regulatory serine-threonine kinases that have
      been implicated in the function of the centrosomes, kinetechores, chromosome
      dynamics, and cytokinesis. In comparison with other tissues, there are high
      levels of expression of Aurora-B and -C in testis. What their respective roles in
      mammalian spermatogenesis are is an open question. Here we describe the
      expression and distribution patterns of the three kinases in mouse testis using
      in situ hybridization and immunohistochemistry. Importantly, the localization of
      Aurora-B is tightly regulated during spermatogenesis, whereas Aurora-C expression
      appears to be testis specific. To address the function of Aurora-B in
      spermatogenesis, we have generated transgenic mice using a pachytene-stage
      specific promoter driving the expression of either wild-type Aurora-B or an
      inactive form of the kinase. Expression of the inactive Aurora-B results in
      abnormal spermatocytes, increased apoptosis, spermatogenic arrest, and
      subfertility defects. The function of Aurora-C may also be targeted in the Aurora
      B transgenic mutants. To address the function of Aurora-C in testis, we generated
      Aurora-C knockout mice by homologous recombination. Remarkably, Aurora-C null
      mice were viable, yet the males had compromised fertility. Aurora-C mutant sperm
      display abnormalities that included heterogenous chromatin condensation, loose
      acrosomes, and blunted heads. These findings indicate that Aurora-B and Aurora-C
      serve specialized functions in mammalian spermatogenesis.

PMID- 17192405
TI  - R5020 and RU486 act as progesterone receptor agonists to enhance Sp1/Sp4
      dependent gene transcription by an indirect mechanism.
AB  - It has been suggested that ligand-dependent gene activation by the progesterone
      receptor (PR) can result from recruitment of PR by the promoter bound Sp1. A
      detailed investigation of the Sp1-dependent agonistic activity of RU486 and R5020
      on the folate receptor (FR) type alpha, p27, thymidine kinase 1 and p21 genes
      reveals a different mechanism. The FR-alpha P4 promoter and the endogenous FR
      alpha gene were up-regulated by the PR agonist R5020 through either PR-A or PR-B.
      The classical antagonist RU486 also activated the promoter but only through PR-B.
      The most proximal (essential) G/C-rich (Sp1 binding) element and the initiator
      region constituted the minimal promoter responsive to PR regulation; substitution
      with a stronger cluster of G/C-rich elements enhanced the magnitude of the PR
      response. In contrast, substitution of the G/C-rich element with a TATA box
      resulted in the loss of regulation by PR. Overexpression of Sp1 and Sp4 but not
      Sp3 enhanced activation of the FR-alpha promoter by PR, knocking down Sp1
      decreased the activation in a manner that was reversed by ectopic Sp1 or Sp4. The
      ligand-dependent action of PR on the promoter was delayed compared with its
      activation of a classical glucocorticoid response element-driven promoter and
      activation of both the promoter and the endogenous FR-alpha gene by PR required
      new protein synthesis. Activation by PR paralleled RNA polymerase II recruitment
      but was not accompanied by either association of PR or a change in the
      association of Sp1 with the endogenous FR-alpha P4 promoter. Similar observations
      were made for PR regulation of the genes encoding p27, thymidine kinase 1, and
      p21. The results contradict the current view of Sp1-dependent gene regulation by
      PR and point to the existence of one or more PR target genes whose promoter and
      cell context(s) must thus be key determinants of the agonistic activity of RU486
      on a large group of important Sp1-dependent downstream target genes.

PMID- 17192406
TI  - Proline-, glutamic acid-, and leucine-rich protein-1/modulator of nongenomic
      activity of estrogen receptor enhances androgen receptor functions through LIM
      only coactivator, four-and-a-half LIM-only protein 2.
AB  - Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1) is a coregulator of
      multiple nuclear receptors. Molecular mechanisms of PELP1 function are not
      completely understood, but its expression is up-regulated in hormonal-dependent
      cancers. Using a yeast two-hybrid screen, we found that four-and-a-half LIM-only
      protein 2 (FHL2) interacted with PELP1. FHL2 is a transcriptional regulator that
      associates with nuclear cofactors, including androgen receptors (ARs), and
      contains an intrinsic activation domain. PELP1 and FHL2 interact in vitro and in
      vivo and colocalize in the nuclear compartment. PELP1 interacts with FHL2 via LIM
      domains 3 and 4 and synergistically enhances the transcriptional activity of
      FHL2. Src kinase is required for PELP1-mediated enhancement of FHL2 functions
      because knockdown of Src kinase expression or function abolished PELP1-mediated
      FHL2 activation functions. PELP1 interacted with AR and enhanced FHL2-mediated AR
      transactivation functions. PELP1 knockdown by small interfering RNA or PELP1
      mutant, which lacks an activation domain, reduced FHL2-mediated AR
      transactivation. Biochemical analyses revealed a complex consisting of PELP1,
      FHL2, and AR in prostate cancer cells. PELP1/MNAR expression was elevated in high
      grade prostate tumors. Our results suggest that PELP1 functions as a molecular
      adaptor, coupling FHL2 with nuclear receptors, and PELP1-FHL2 interactions may
      have a role in prostate cancer progression.

PMID- 17192408
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 17192407
TI  - Foxl2 up-regulates aromatase gene transcription in a female-specific manner by
      binding to the promoter as well as interacting with ad4 binding
      protein/steroidogenic factor 1.
AB  - Increasing evidence suggests the crucial role of estrogen in ovarian
      differentiation of nonmammalian vertebrates including fish. The present study has
      investigated the plausible role of Foxl2 in ovarian differentiation through
      transcriptional regulation of aromatase gene, using monosex fry of tilapia. Foxl2
      expression is sexually dimorphic, like Cyp19a1, colocalizing with Cyp19a1 and
      Ad4BP/SF-1 in the stromal cells and interstitial cells in gonads of normal XX and
      sex-reversed XY fish, before the occurrence of morphological sex differentiation.
      Under in vitro conditions, Foxl2 binds to the sequence ACAAATA in the promoter
      region of the Cyp19a1 gene directly through its forkhead domain and activates the
      transcription of Cyp19a1 with its C terminus. Foxl2 can also interact through the
      forkhead domain with the ligand-binding domain of Ad4BP/SF-1 to form a
      heterodimer and enhance the Ad4BP/SF-1 mediated Cyp19a1 transcription. Disruption
      of endogenous Foxl2 in XX tilapia by overexpression of its dominant negative
      mutant (M3) induces varying degrees of testicular development with occasional sex
      reversal from ovary to testis. Such fish display reduced expression of Cyp19a1 as
      well as a drop in the serum levels of 17beta-estradiol and 11-ketotestosterone.
      Although the XY fish with wild-type tilapia Foxl2 (tFoxl2) overexpression never
      exhibited a complete sex reversal, there were significant structural changes,
      such as tissue degeneration, somatic cell proliferation, and induction of
      aromatase, with increased serum levels of 17beta-estradiol and 11
      ketotestosterone. Altogether, these results suggest that Foxl2 plays a decisive
      role in the ovarian differentiation of the Nile tilapia by regulating aromatase
      expression and possibly the entire steroidogenic pathway.

PMID- 17192409
TI  - Identification of an N-acetylglucosamine transporter that mediates hyphal
      induction in Candida albicans.
AB  - The sugar N-acetylglucosamine (GlcNAc) plays an important role in nutrient
      sensing and cellular regulation in a wide range of organisms from bacteria to
      humans. In the fungal pathogen Candida albicans, GlcNAc induces a morphological
      transition from budding to hyphal growth. Proteomic comparison of plasma membrane
      proteins from buds and from hyphae induced by GlcNAc identified a novel hyphal
      protein (Ngt1) with similarity to the major facilitator superfamily of
      transporters. An Ngt1-GFP fusion was detected in the plasma membrane after
      induction with GlcNAc, but not other related sugars. Ngt1-GFP was also induced by
      macrophage phagocytosis, suggesting a role for the GlcNAc response in signaling
      entry into phagolysosomes. NGT1 is needed for efficient GlcNAc uptake and for the
      ability to induce hyphae at low GlcNAc concentrations. High concentrations of
      GlcNAc could bypass the need for NGT1 to induce hyphae, indicating that elevated
      intracellular levels of GlcNAc induce hyphal formation. Expression of NGT1 in
      Saccharomyces cerevisiae promoted GlcNAc uptake, indicating that Ngt1 acts
      directly as a GlcNAc transporter. Transport mediated by Ngt1 was specific, as
      other sugars could not compete for the uptake of GlcNAc. Thus, Ngt1 represents
      the first eukaryotic GlcNAc transporter to be discovered. The presence of NGT1
      homologues in the genome sequences of a wide range of eukaryotes from yeast to
      mammals suggests that they may also function in the cellular processes regulated
      by GlcNAc, including those that underlie important diseases such as cancer and
      diabetes.

PMID- 17192411
TI  - Two mammalian Sec16 homologues have nonredundant functions in endoplasmic
      reticulum (ER) export and transitional ER organization.
AB  - Budding yeast Sec16 is a large peripheral endoplasmic reticulum (ER) membrane
      protein that functions in generating COPII transport vesicles and in clustering
      COPII components at transitional ER (tER) sites. Sec16 interacts with multiple
      COPII components. Although the COPII assembly pathway is evolutionarily
      conserved, Sec16 homologues have not been described in higher eukaryotes. Here,
      we show that mammalian cells contain two distinct Sec16 homologues: a large
      protein that we term Sec16L and a smaller protein that we term Sec16S. These
      proteins localize to tER sites, and an N-terminal region of each protein is
      necessary and sufficient for tER localization. The Sec16L and Sec16S genes are
      both expressed in every tissue examined, and both proteins are required in HeLa
      cells for ER export and for normal tER organization. Sec16L resembles yeast Sec16
      in having a C-terminal conserved domain that interacts with the COPII coat
      protein Sec23, but Sec16S lacks such a C-terminal conserved domain.
      Immunoprecipitation data indicate that Sec16L and Sec16S are each present at
      multiple copies in a heteromeric complex. We infer that mammalian cells have
      preserved and extended the function of Sec16.

PMID- 17192410
TI  - Asymmetric localization of calpain 2 during neutrophil chemotaxis.
AB  - Chemoattractants induce neutrophil polarization through localized polymerization
      of F-actin at the leading edge. The suppression of rear and lateral protrusions
      is required for efficient chemotaxis and involves the temporal and spatial
      segregation of signaling molecules. We have previously shown that the
      intracellular calcium-dependent protease calpain is required for cell migration
      and is involved in regulating neutrophil chemotaxis. Here, we show that primary
      neutrophils and neutrophil-like HL-60 cells express both calpain 1 and calpain 2
      and that chemoattractants induce the asymmetric recruitment of calpain 2, but not
      calpain 1, to the leading edge of polarized neutrophils and differentiated HL-60
      cells. Using time-lapse microscopy, we show that enrichment of calpain 2 at the
      leading edge occurs during early pseudopod formation and that its localization is
      sensitive to changes in the chemotactic gradient. We demonstrate that calpain 2
      is recruited to lipid rafts and that cholesterol depletion perturbs calpain 2
      localization, suggesting that its enrichment at the front requires proper
      membrane organization. Finally, we show that catalytic activity of calpain is
      required to limit pseudopod formation in the direction of chemoattractant and for
      efficient chemotaxis. Together, our findings identify calpain 2 as a novel
      component of the frontness signal that promotes polarization during chemotaxis.

PMID- 17192412
TI  - Atg19 mediates a dual interaction cargo sorting mechanism in selective autophagy.
AB  - Autophagy is a catabolic membrane-trafficking mechanism conserved in all
      eukaryotic cells. In addition to the nonselective transport of bulk cytosol,
      autophagy is responsible for efficient delivery of the vacuolar enzyme Ape1
      precursor (prApe1) in the budding yeast Saccharomyces cerevisiae, suggesting the
      presence of a prApe1 sorting machinery. Sequential interactions between Atg19
      Atg11 and Atg19-Atg8 pairs are thought responsible for targeting prApe1 to the
      vesicle formation site, the preautophagosomal structure (PAS), and loading it
      into transport vesicles, respectively. However, the different patterns of prApe1
      transport defect seen in the atg11Delta and atg19Delta strains seem to be
      incompatible with this model. Here we report that prApe1 could not be targeted to
      the PAS and failed to be delivered into the vacuole in atg8Delta atg11Delta
      double knockout cells regardless of the nutrient conditions. We postulate that
      Atg19 mediates a dual interaction prApe1-sorting mechanism through independent,
      instead of sequential, interactions with Atg11 and Atg8. In addition, to
      efficiently deliver prApe1 to the vacuole, a proper interaction between Atg11 and
      Atg9 is indispensable. We speculate that Atg11 may elicit a cargo-loading signal
      and induce Atg9 shuttling to a specific PAS site, where Atg9 relays the signal
      and recruits other Atg proteins to induce vesicle formation.

PMID- 17192413
TI  - The Cullin3 ubiquitin ligase functions as a Nedd8-bound heterodimer.
AB  - Cullins are members of a family of scaffold proteins that assemble multisubunit
      ubiquitin ligase complexes to confer substrate specificity for the ubiquitination
      pathway. Cullin3 (Cul3) forms a catalytically inactive BTB-Cul3-Rbx1 (BCR)
      ubiquitin ligase, which becomes functional upon covalent attachment of the
      ubiquitin homologue neural-precursor-cell-expressed and developmentally down
      regulated 8 (Nedd8) near the C terminus of Cul3. Current models suggest that
      Nedd8 activates cullin complexes by providing a recognition site for a ubiquitin
      conjugating enzyme. Based on the following evidence, we propose that Nedd8
      activates the BCR ubiquitin ligase by mediating the dimerization of Cul3. First,
      Cul3 is found as a neddylated heterodimer bound to a BTB domain-containing
      protein in vivo. Second, the formation of a Cul3 heterodimer is mediated by a
      Nedd8 molecule, which covalently attaches itself to one Cul3 molecule and binds
      to the winged-helix B domain at the C terminus of the second Cul3 molecule.
      Third, complementation experiments revealed that coexpression of two distinct
      nonfunctional Cul3 mutants can rescue the ubiquitin ligase function of the BCR
      complex. Likewise, a substrate of the BCR complex binds heterodimeric Cul3,
      suggesting that the Cul3 complex is active as a dimer. These findings not only
      provide insight into the architecture of the active BCR complex but also suggest
      assembly as a regulatory mechanism for activation of all cullin-based ubiquitin
      ligases.

PMID- 17192415
TI  - Lack of adenomatous polyposis coli protein correlates with a decrease in cell
      migration and overall changes in microtubule stability.
AB  - Most sporadic colorectal tumors carry truncation mutations in the adenomatous
      polyposis coli (APC) gene. The APC protein is involved in many processes that
      govern gut tissue. In addition to its involvement in the regulation of beta
      catenin, APC is a cytoskeletal regulator with direct and indirect effects on
      microtubules. Cancer-related truncation mutations lack direct and indirect
      binding sites for microtubules in APC, suggesting that loss of this function
      contributes to defects in APC-mutant cells. In this study, we show that loss of
      APC results in disappearance of cellular protrusions and decreased cell
      migration. These changes are accompanied by a decrease in overall microtubule
      stability and also by a decrease in posttranslationally modified microtubules in
      the cell periphery particularly the migrating edge. Consistent with the ability
      of APC to affect cell shape, the overexpression of APC in cells can induce
      cellular protrusions. These data demonstrate that cell migration and microtubule
      stability are linked to APC status, thereby revealing a weakness in APC-deficient
      cells with potential therapeutic implications.

PMID- 17192414
TI  - Ribosome biogenesis is sensed at the Start cell cycle checkpoint.
AB  - In the yeast Saccharomyces cerevisiae it has long been thought that cells must
      reach a critical cell size, called the "setpoint," in order to allow the Start
      cell cycle transition. Recent evidence suggests that this setpoint is lowered
      when ribosome biogenesis is slowed. Here we present evidence that yeast can sense
      ribosome biogenesis independently of mature ribosome levels and protein synthetic
      capacity. Our results suggest that ribosome biogenesis directly promotes passage
      through Start through Whi5, the yeast functional equivalent to the human tumor
      suppressor Rb. When ribosome biogenesis is inhibited, a Whi5-dependent mechanism
      inhibits passage through Start before significant decreases in both the number of
      ribosomes and in overall translation capacity of the cell become evident. This
      delay at Start in response to decreases in ribosome biogenesis occurs
      independently of Cln3, the major known Whi5 antagonist. Thus ribosome biogenesis
      may be sensed at multiple steps in Start regulation. Ribosome biogenesis may thus
      both delay Start by increasing the cell size setpoint and independently may
      promote Start by inactivating Whi5.

PMID- 17192416
TI  - Assessment of an optimized mycobacterial interspersed repetitive- unit-variable
      number tandem-repeat typing system combined with spoligotyping for population
      based molecular epidemiology studies of tuberculosis.
AB  - An optimized set of 24 mycobacterial interspersed repetitive-unit-variable-number
      tandem-repeat (MIRU-VNTR) loci, including a discriminatory subset of 15 loci, has
      recently been defined for the typing of Mycobacterium tuberculosis. Here, we
      evaluated the performances of this MIRU-VNTR typing system in combination with
      spoligotyping for the detection of transmission chains in a population-based
      study comprising 91% of culture-confirmed tuberculosis patients reported in 2003
      in Hamburg, Germany. Of the 154 isolates investigated, more than 90% had high
      IS6110 copy numbers (>/=6). IS6110 restriction fragment length polymorphism
      (RFLP) typing resulted in 13 clusters, 5 of which had a confirmed epidemiological
      link. All five, as well as six of the eight IS6110 clusters with no identified
      epidemiological link, were perfectly matched by MIRU-VNTR typing with the 24
      loci. Two IS6110 clusters were split by differences into 6 to 12 MIRU-VNTR loci,
      clearly supporting the absence of a link, as judged by contact tracing data. In
      contrast, only one MIRU-VNTR cluster, grouping what were probably
      epidemiologically unlinked isolates, was split by IS6110 RFLP. However, these
      isolates were also distinguished by spoligotyping. Both the optimized 24-locus
      and 15-locus sets thus showed a comparable to slightly better predictive value,
      especially when combined with spoligotyping, than the current gold standard
      IS6110 RFLP for the study of tuberculosis transmission in Hamburg. Because the
      epidemiological characteristics of this setting are similar to those of many
      developed countries, these results support the wide applicability of this real
      time genotyping approach for population-based studies of M. tuberculosis
      transmission.

PMID- 17192417
TI  - Distinct antimicrobial resistance patterns and antimicrobial resistance-harboring
      genes according to genomic species of Acinetobacter isolates.
AB  - Using 58 isolates of Acinetobacter species recovered from a university hospital
      between August 2004 and March 2005, we performed genomic identification by
      amplified rRNA gene restriction analysis (ARDRA) and investigated the existence
      of metallo-beta-lactamase (MBL) producers and extended-spectrum beta-lactamase
      (ESBL) producers. Genomic species identification of Acinetobacter strains using
      ARDRA showed that 40 strains were genomic species 2 (Acinetobacter baumannii), 9
      were 13 sensu Tjernberg and Ursing (13TU), 5 were Acinetobacter phenon 6/ct 13TU,
      and 4 were Acinetobacter genospecies 3. Among 58 strains, 13 isolates were MBL
      producers carrying bla(IMP-1) or bla(VIM-2) and 13 isolates were ESBL producers
      carrying bla(PER-1). Notably, the MBL producers were mostly 13TU, Acinetobacter
      phenon 6/ct 13TU, and Acinetobacter genospecies 3, which showed susceptibility to
      ciprofloxacin and ampicillin-sulbactam. However, 12 of 13 strains carrying
      bla(PER-1) were A. baumannii, showing multidrug resistance. The data revealed
      that the antimicrobial resistance patterns and resistance-harboring genes of
      Acinetobacter species are remarkably distinct according to the genomic species of
      Acinetobacter isolates.

PMID- 17192419
TI  - Gordonia terrae: a difficult-to-diagnose emerging pathogen?

PMID- 17192418
TI  - Genotypic analysis of invasive Streptococcus pneumoniae from Mali, Africa, by
      semiautomated repetitive-element PCR and pulsed-field gel electrophoresis.
AB  - As part of a large, ongoing study of invasive infections in pediatric patients in
      Bamako, Mali, 106 cases of invasive pneumococcal disease were identified from
      June 2002 to July 2003 (J. D. Campbell et al., Pediatr. Infect. Dis. J. 23:642
      649, 2004). Of the 12 serotypes present, the majority of isolates were not
      contained in PCV7 (the 7-valent pneumococcal conjugate vaccine), including 1
      isolate that was serotype 1, 12 isolates that were serotype 2, 58 isolates that
      were serotype 5, 7 isolates that were serotype 7F, and 1 isolate that was
      serotype 12F. To determine whether clonal dissemination of the predominant
      serotypes had taken place, genotyping was performed on 100 S. pneumoniae isolates
      by using two methods: pulsed-field gel electrophoresis (PFGE) of SmaI-digested
      genomic DNA, and the Bacterial Barcodes repetitive-element PCR (rep-PCR) method.
      Criteria for delineating rep-PCR genotypes were established such that isolates of
      different serotypes were generally not grouped together. The two methods were
      equally discriminatory within a given pneumococcal serotype. PFGE separated the
      isolates into 15 genotypes and 7 subtypes; rep-PCR separated isolates into 15
      genotypes and 6 subtypes. Using either method, isolates within serotypes 2, 5,
      and 7 formed three large, separate clusters containing 1 genotype each. Both
      methods further distinguished related subtypes within serotypes 2 and 5.
      Interestingly, one of the PFGE subtypes of serotype 5 is indistinguishable from
      the Columbia(5)-19 clone circulating in Latin America since 1994. The data
      support that serotypes 2 and 5 were likely to be the result of dissemination of
      particular clones, some of which are responsible for invasive disease over a
      broad population range.

PMID- 17192420
TI  - Staphylococcal cassette chromosome mec and Panton-Valentine leukocidin
      characterization of methicillin-resistant Staphylococcus aureus clones.
AB  - Staphylococcal cassette chromosome mec (SCCmec) types and Panton-Valentine
      leukocidin (PVL) gene carriage were compared among suspected community-associated
      methicillin-resistant Staphylococcus aureus MRSA (CA-MRSA) and health care
      associated MRSA (HA-MRSA) isolates. CA-MRSA isolates carried the SCCmec type IV
      complex, and most were PVL positive. The HA-MRSA isolates carried the SCCmec type
      II complex and did not harbor the PVL genes.

PMID- 17192421
TI  - Involvement of the myelin-associated inhibitor Nogo-A in early cortical
      development and neuronal maturation.
AB  - Nogo-A is a myelin-associated protein expressed by neurons and myelinating mature
      oligodendrocytes in the central nervous system. Although most research has
      focused on the participation of Nogo-A in the prevention of axonal regeneration
      and plasticity in the adult, little attention has been paid to the putative
      functions of Nogo-A during embryonic development. Here we examined the general
      pattern and cell-specific distribution of Nogo-A in the prenatal mouse
      telencephalon. In addition, we studied the development of the major axon tracts
      and radial and tangential migration in Nogo-A/B/C knockout mice. The pattern of
      Nogo-A showed distinct distribution in radial glia and postmitotic neurons, in
      which it is particularly enriched in developing axons. Similarly, Nogo-A was
      enriched at the leading process of tangentially migrating interneurons but not
      detectable in radial migrating neurons. Although a low level of Nogo-A appears to
      be on the surface of many cortical neurons, most proteins have intracellular
      localization. In Nogo-deficient background, neurons displayed early polarization
      and increased branching in vitro, probably reflecting a cell-intrinsic role of
      Nogo proteins in branching reduction, and early tangential migration was delayed.
      On the basis of these observations, we propose that Nogo proteins, particularly
      Nogo-A, are involved in multiple processes during cortical development.

PMID- 17192422
TI  - OKL38 is an oxidative stress response gene stimulated by oxidized phospholipids.
AB  - Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) is
      present in oxidative modified LDL and accumulates in lesions of many chronic
      inflammatory diseases, such as atherosclerosis. In a microarray study, OxPAPC has
      been demonstrated to modulate the expression of >700 genes in human aortic
      endothelial cells. We found that the levels of mRNA for OKL38 [also named Bone
      marrow Derived Growth Factor (BDGI)], a tumor growth inhibitor, were strongly
      increased by OxPAPC. Here, we report that OKL38 is regulated by an oxidative
      signal induced by OxPAPC and its component lipid 1-palmitoyl-2-epoxyisoprostane
      E2-sn-glycero-3-phosphorylcholine. The stimulation of OKL38 by OxPAPC depends on
      superoxide production, because the NADPH oxidase (Nox) inhibitor apocynin and the
      superoxide scavenger N-acetyl cysteine block this stimulation. Oxidative stress
      by tert-butylhydroquinone treatment also induced the expression of OKL38. The
      stimulation of OKL38 expression by OxPAPC is mediated via transcription factor
      nuclear factor E2-related factor (Nrf2), a common factor involved in the
      regulation of oxidative stress-stimulated genes. Activation of Nrf2 induces the
      expression of OKL38, whereas small interfering RNA knockdown of Nrf2 blocks the
      stimulation of OKL38 by OxPAPC. Our results suggest that OKL38 is regulated via
      the Nox/Nrf2 pathway in response to oxidative stress stimuli.

PMID- 17192423
TI  - Cholesteryl ester transfer protein and hyperalphalipoproteinemia in Caucasians.
AB  - It is unclear whether cholesteryl ester transfer protein (CETP) contributes to
      high density lipoprotein cholesterol (HDL-C) levels in hyperalphalipoproteinemia
      (HALP) in Caucasians. Moreover, even less is known about the effects of
      hereditary CETP deficiency in non-Japanese. We studied 95 unrelated Caucasian
      individuals with HALP. No correlations between CETP concentration or activity and
      HDL-C were identified. Screening for CETP gene defects led to the identification
      of heterozygosity for a novel splice site mutation in one individual. Twenty-five
      heterozygotes for this mutation showed reduced CETP concentration (-40%) and
      activity (-50%) and a 35% increase of HDL-C compared with family controls. The
      heterozygotes presented with an isolated high HDL-C, whereas the remaining
      subjects exhibited a typical high HDL-C/low-triglyceride phenotype. The increase
      of HDL-C in the CETP-deficient heterozygotes was primarily attributable to
      increased high density lipoprotein containing apolipoprotein A-I and A-II
      (LpAI:AII) levels, contrasting with an increase in both high density lipoprotein
      containing apolipoprotein A-I only and LpAI:AII in the other group. This study
      suggests the absence of a relationship between CETP and HDL-C levels in
      Caucasians with HALP. The data furthermore indicate that genetic CETP deficiency
      is rare among Caucasians and that this disorder presents with a phenotype that is
      different from that of subjects with HALP who have no mutation in the CETP gene.

PMID- 17192424
TI  - Neuromuscular development in the absence of programmed cell death: phenotypic
      alteration of motoneurons and muscle.
AB  - The widespread, massive loss of developing neurons in the central and peripheral
      nervous system of birds and mammals is generally considered to be an evolutionary
      adaptation. However, until recently, models for testing both the immediate and
      long-term consequences of preventing this normal cell loss have not been
      available. We have taken advantage of several methods for preventing neuronal
      death in vivo to ask whether rescued neurons [e.g., motoneurons (MNs)]
      differentiate normally and become functionally incorporated into the nervous
      system. Although many aspects of MN differentiation occurred normally after the
      prevention of cell death (including the expression of several motoneuron-specific
      markers, axon projections into the ventral root and peripheral nerves,
      ultrastructure, dendritic arborization, and afferent axosomatic synapses), other
      features of the neuromuscular system (MNs and muscle) were abnormal. The cell
      bodies and axons of MNs were smaller than normal, many MN axons failed to become
      myelinated or to form functional synaptic contacts with target muscles, and a
      subpopulation of rescued cells were transformed from alpha- to gamma-like MNs.
      Additionally, after the rescue of MNs in myogenin glial cell line-derived
      neurotrophic factor (MyoGDNF) transgenic mice, myofiber differentiation of
      extrafusal skeletal muscle was transformed and muscle physiology and motor
      behaviors were abnormal. In contrast, extrafusal myofiber phenotype, muscle
      physiology, and (except for muscle strength tests) motor behaviors were all
      normal after the rescue of MNs by genetic deletion of the proapoptotic gene Bax.
      However, there was an increase in intrafusal muscle fibers (spindles) in Bax
      knock-out versus both wild-type and MyoGDNF mice. Together, these data indicate
      that after the prevention of MN death, the neuromuscular system becomes
      transformed in novel ways to compensate for the presence of the thousands of
      excess cells.

PMID- 17192425
TI  - Deficits in synaptic transmission and learning in amyloid precursor protein (APP)
      transgenic mice require C-terminal cleavage of APP.
AB  - Synaptic dysfunction has been shown to be one of the earliest correlates of
      disease progression in animal models of Alzheimer's disease. Amyloid-beta protein
      (Abeta) is thought to play an important role in disease-related synaptic
      dysfunction, but the mechanism by which Abeta leads to synaptic dysfunction is
      not understood. Here we describe evidence that cleavage of APP in the C terminus
      may be necessary for the deficits present in APP transgenic mice. In APP
      transgenic mice with a mutated cleavage site at amino acid 664, normal synaptic
      transmission, synaptic plasticity, and learning were maintained despite the
      presence of elevated levels of APP, Abeta42, and even plaque accumulation. These
      results indicate that cleavage of APP may play a critical role in the development
      of synaptic and behavioral dysfunction in APP transgenic mice.

PMID- 17192426
TI  - Temporal discontiguity is neither necessary nor sufficient for learning-induced
      effects on adult neurogenesis.
AB  - Some, but not all, types of learning and memory can influence neurogenesis in the
      adult hippocampus. Trace eyeblink conditioning has been shown to enhance the
      survival of new neurons, whereas delay eyeblink conditioning has no such effect.
      The key difference between the two training procedures is that the conditioning
      stimuli are separated in time during trace but not delay conditioning. These
      findings raise the question of whether temporal discontiguity is necessary for
      enhancing the survival of new neurons. Here we used two approaches to test this
      hypothesis. First, we examined the influence of a delay conditioning task in
      which the duration of the conditioned stimulus (CS) was increased nearly twofold,
      a procedure that critically engages the hippocampus. Although the CS and
      unconditioned stimulus are contiguous, this very long delay conditioning
      procedure increased the number of new neurons that survived. Second, we examined
      the influence of learning the trace conditioned response (CR) after having
      acquired the CR during delay conditioning, a procedure that renders trace
      conditioning hippocampal-independent. In this case, trace conditioning did not
      enhance the survival of new neurons. Together, these results demonstrate that
      associative learning increases the survival of new neurons in the adult
      hippocampus, regardless of temporal contiguity.

PMID- 17192428
TI  - Large functional variability in cockroach photoreceptors: optimization to low
      light levels.
AB  - The compound eyes of insects contain photoreceptors in small eyelets, ommatidia.
      The photoreceptors generally vary very little from ommatidium to ommatidium.
      However, in the large compound eyes of the cockroach (Periplaneta americana),
      previous studies have shown large differences in the optical structure between
      the ommatidia. The anatomy suggests pooling of 6-20 photoreceptor signals into
      one second-order cell in the first synapse. Here, we show and characterize an
      unexpectedly large and seemingly random functional variability in the cockroach
      photoreceptors in terms of sensitivity, adaptation speed, angular sensitivity,
      and signal-to-noise ratio. We also investigate the implications of action
      potentials, triggered by the light-induced membrane depolarization in the
      photoreceptor axons. The combination of the functional features reported here is
      unique among the compound eyes. Recordings from the proximal parts of the thin
      and long photoreceptor axons or small and distant second-order neurons are not
      practical with the present methods. To alleviate this lack of data, we used
      computer simulations mimicking the functional variability, spike coding, and
      pooling of 12 photoreceptor signals, on the basis of our recordings from the
      photoreceptor somata and distal axons. The predicted responses of a simulated
      second-order cell follow surprisingly reliably the simulated light stimuli when
      compared with a simulation of functionally identical photoreceptors. We
      hypothesize that cockroach photoreceptors use action potential coding and a kind
      of population coding scheme for making sense of the inherently unreliable light
      signals at low luminance and for optimization of vision in its mainly dim living
      conditions.

PMID- 17192427
TI  - Metabotropic glutamate receptors differentially regulate GABAergic inhibition in
      thalamus.
AB  - Thalamic interneurons and thalamic reticular nucleus (TRN) neurons provide
      inhibitory innervation of thalamocortical cells that significantly influence
      thalamic gating. The local interneurons in the dorsal lateral geniculate nucleus
      (dLGN) give rise to two distinct synaptic outputs: classical axonal and
      dendrodendritic. Activation of metabotropic glutamate receptors (mGluRs) by
      agonists or optic tract stimulation increases the output of these presynaptic
      dendrites leading to increased inhibition of thalamocortical neurons. The present
      study was aimed to evaluate the actions of specific mGluRs on inhibitory GABA
      mediated signaling. We found that the group I mGluR (mGluR(1,5)) agonist (RS)-3,5
      dihydroxyphenylglycine (DHPG) or optic tract stimulation produced a robust
      increase in spontaneous IPSCs (sIPSCs) in thalamocortical neurons that was
      attenuated by the selective mGluR(5) antagonist 2-methyl-6
      (phenylethynyl)pyridine hydrochloride (MPEP). In contrast, the group II mGluR
      (mGluR(2,3)) agonists (2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) or
      (2S,2'R,3'R)-2-(2'3'-dicarboxycyclopropyl)glycine (DCG-IV) suppressed the
      frequency of sIPSCs. In addition, mGluR(1,5) agonist DHPG produced
      depolarizations and mGluR(2/3) agonists APDC or L-CCG-I [(2S,1'S,2'S)-2
      (carboxycyclopropyl)glycine] produced hyperpolarizations in dLGN interneurons.
      Furthermore, the enhanced sIPSC activity by optic tract stimulation was reduced
      when paired with corticothalamic fiber stimulation. The present data indicate
      that activation of specific mGluR subtypes differentially regulates inhibitory
      activity via different synaptic pathways. Our results suggest that activation of
      specific mGluR subtypes can upregulate or downregulate inhibitory activity in
      thalamic relay neurons, and these actions likely shape excitatory synaptic
      integration and thus regulate information transfer through thalamocortical
      circuits.

PMID- 17192430
TI  - The endurance and selectivity of spatial patterns of long-term
      potentiation/depression in dendrites under homeostatic synaptic plasticity.
AB  - We investigated analytically and numerically the interplay between two opposing
      forms of synaptic plasticity: positive-feedback, long-term
      potentiation/depression (LTP/LTD), and negative-feedback, homeostatic synaptic
      plasticity (HSP). A detailed model of a CA1 pyramidal neuron, with numerous HSP
      modifiable dendritic synapses, demonstrates that HSP may have an important role
      in selecting which spatial patterns of LTP/LTD are to last. Several measures are
      developed for predicting the net residual potentiation/depression after HSP from
      the initial spatial pattern of LTP/LTD. Under a local dendritic HSP mechanism,
      sparse patterns of LTP/LTD, which we show, using information theoretical tools,
      to have a significant impact on the output of the postsynaptic neuron, will
      persist. In contrast, spatially clustered patterns with a smaller impact on the
      output will diminish. A global somatic HSP mechanism, conversely, will favor
      distally occurring LTP/LTDs over proximal ones. Despite the negative-feedback
      nature of HSP, under both local and global HSP, numerous synaptic
      potentiations/depressions can persist. These experimentally testable results
      imply that HSP could be significantly involved in shaping the spatial
      distribution of synaptic weights in the dendrites and not just normalizing it, as
      is currently believed.

PMID- 17192429
TI  - Upregulation of the neuron-specific K+/Cl- cotransporter expression by
      transcription factor early growth response 4.
AB  - The expression of the neuron-specific K+/Cl- cotransporter (KCC2) is restricted
      to the CNS and is strongly upregulated during neuronal maturation, yielding a low
      intracellular chloride concentration that is required for fast synaptic
      inhibition in adult neurons. To elucidate the mechanisms of KCC2 gene regulation,
      we analyzed the KCC2 (alias Slc12a5) promoter and proximal intron-1 regions and
      revealed 10 candidate transcription factor binding sites that are highly
      conserved in mammalian KCC2 genes. Here we focus on one of these factors, early
      growth response 4 (Egr4), which shows a similar developmental upregulation in CNS
      neurons as KCC2. KCC2 luciferase reporter constructs containing the Egr4 site
      (Egr4(KCC2)) were strongly induced by Egr4 overexpression in neuro-2a
      neuroblastoma cells and in cultured neurons. Egr4-mediated induction was
      decreased significantly by point-mutating the Egr4(KCC2). Insertion of Egr4(KCC2)
      into the KCC2 basal promoter in the endogenous reverse, but not in the opposite,
      orientation reestablished Egr4-mediated induction. Electrophoretic mobility shift
      assay confirmed specific Egr4 binding to Egr4(KCC2). Interference RNA-mediated
      knock-down of Egr4 and a dominant-negative isoform of Egr4 significantly
      inhibited KCC2 reporter induction and endogenous KCC2 expression in cultured
      neurons. Together, the results indicate an important role for Egr4 in the
      developmental upregulation of KCC2 gene expression.

PMID- 17192431
TI  - Phase precession in hippocampal interneurons showing strong functional coupling
      to individual pyramidal cells.
AB  - Although hippocampal interneurons typically do not show discrete regions of
      elevated firing in an environment, such as seen in pyramidal cell place fields,
      they do exhibit significant spatial modulation (McNaughton et al., 1983a). Strong
      monosynaptic coupling between pyramidal neurons and nearby interneurons in the
      CA1 stratum pyramidale has been strongly implicated on the basis of significant,
      short-latency peaks in cross-correlogram plots (Csicsvari et al., 1998).
      Furthermore, interneurons receiving a putative monosynaptic connection from a
      simultaneously recorded pyramidal cell appear to inherit the spatial modulation
      of the latter (Marshall et al., 2002). Buzsaki and colleagues hypothesize that
      interneurons may also adopt the firing phase dynamics of their afferent place
      cells, which show a phase shift relative to the hippocampal theta rhythm as a rat
      passes through the place field ("phase precession"). This study confirms and
      extends the previous reports by showing that interneurons in the dorsal and
      middle hippocampus with putative monosynaptic connections with place cells
      recorded on the same tetrode share other properties with their pyramidal cell
      afferents, including the spatial scale of the place field of pyramidal cell, a
      characteristic of the septotemporal level of the hippocampus from which the cells
      are recorded, and the rate of phase precession, which is slower in middle
      regions. Furthermore, variations in pyramidal cell place field scale within each
      septotemporal level attributable to task variations are similarly associated with
      variations in interneuron place field scale. The available data strongly suggest
      that spatial selectivity of CA1 stratum pyramidale interneurons is inherited from
      a small cluster of local pyramidal cells and is not a consequence of spatially
      selective synaptic input from CA3 or other sources.

PMID- 17192432
TI  - Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of
      neurotransmitter release in central and neuromuscular synapses.
AB  - Biochemical and genetic data suggest that synaptotagmin-2 functions as a Ca2+
      sensor for fast neurotransmitter release in caudal brain regions, but animals
      and/or synapses lacking synaptotagmin-2 have not been examined. We have now
      generated mice in which the 5' end of the synaptotagmin-2 gene was replaced by
      lacZ. Using beta-galactosidase as a marker, we show that, consistent with
      previous studies, synaptotagmin-2 is widely expressed in spinal cord, brainstem,
      and cerebellum, but is additionally present in selected forebrain neurons,
      including most striatal neurons and some hypothalamic, cortical, and hippocampal
      neurons. Synaptotagmin-2-deficient mice were indistinguishable from wild-type
      littermates at birth, but subsequently developed severe motor dysfunction, and
      perished at approximately 3 weeks of age. Electrophysiological studies in
      cultured striatal neurons revealed that the synaptotagmin-2 deletion slowed the
      kinetics of evoked neurotransmitter release without altering the total amount of
      release. In contrast, synaptotagmin-2-deficient neuromuscular junctions (NMJs)
      suffered from a large reduction in evoked release and changes in short-term
      synaptic plasticity. Furthermore, in mutant NMJs, the frequency of spontaneous
      miniature release events was increased both at rest and during stimulus trains.
      Viewed together, our results demonstrate that the synaptotagmin-2 deficiency
      causes a lethal impairment in synaptic transmission in selected synapses. This
      impairment, however, is less severe than that produced in forebrain neurons by
      deletion of synaptotagmin-1, presumably because at least in NMJs, synaptotagmin-1
      is coexpressed with synaptotagmin-2, and both together mediate fast Ca2+
      triggered release. Thus, synaptotagmin-2 is an essential synaptotagmin isoform
      that functions in concert with other synaptotagmins in the Ca2+ triggering of
      neurotransmitter release.

PMID- 17192433
TI  - Bidirectional activity-dependent regulation of neuronal ion channel
      phosphorylation.
AB  - Activity-dependent dephosphorylation of neuronal Kv2.1 channels yields
      hyperpolarizing shifts in their voltage-dependent activation and homoeostatic
      suppression of neuronal excitability. We recently identified 16 phosphorylation
      sites that modulate Kv2.1 function. Here, we show that in mammalian neurons,
      compared with other regulated sites, such as serine (S)563, phosphorylation at
      S603 is supersensitive to calcineurin-mediated dephosphorylation in response to
      kainate-induced seizures in vivo, and brief glutamate stimulation of cultured
      hippocampal neurons. In vitro calcineurin digestion shows that supersensitivity
      of S603 dephosphorylation is an inherent property of Kv2.1. Conversely,
      suppression of neuronal activity by anesthetic in vivo causes
      hyperphosphorylation at S603 but not S563. Distinct regulation of individual
      phosphorylation sites allows for graded and bidirectional homeostatic regulation
      of Kv2.1 function. S603 phosphorylation represents a sensitive bidirectional
      biosensor of neuronal activity.

PMID- 17192434
TI  - An oculomotor decision process revealed by functional magnetic resonance imaging.
AB  - It is not known how the brain decides to act on moving objects. We demonstrated
      previously that neurons in the macaque supplementary eye field (SEF) reflect the
      rule of ocular baseball, a go/nogo task in which eye movements signal the rule
      guided interpretation of the trajectory of a target. In ocular baseball, subjects
      must decide whether to pursue a moving spot target with an eye movement after
      discriminating whether the target will cross a distal, visible line segment. Here
      we identify cortical regions active during the ocular baseball task using event
      related human functional magnetic resonance imaging (fMRI) and concurrent eye
      movement monitoring. Task-related activity was observed in the SEF, the frontal
      eye field (FEF), the superior parietal lobule (SPL), and the right ventrolateral
      prefrontal cortex (VLPFC). The SPL and right VLPFC showed heightened activity
      only during ocular baseball, despite identical stimuli and oculomotor demands in
      the control task, implicating these areas in the decision process. Furthermore,
      the right VLPFC but not the SPL showed the greatest activation during the nogo
      decision trials. This suggests both a functional dissociation between these areas
      and a role for the right VLPFC in rule-guided inhibition of behavior. In the SEF
      and FEF, activity was similar for ocular baseball and a control eye-movement
      task. We propose that, although the SEF reflects the ocular baseball rule, both
      areas in humans are functionally closer to motor processing than the SPL and the
      right VLPFC. By recording population activity with fMRI during the ocular
      baseball task, we have revealed the cortical substrate of an oculomotor decision
      process.

PMID- 17192435
TI  - Regulation of rod phototransduction machinery by ciliary neurotrophic factor.
AB  - Ciliary neurotrophic factor (CNTF) promotes photoreceptor survival but also
      suppresses electroretinogram (ERG) responses. This has caused concerns about
      whether CNTF is detrimental to the function of photoreceptors because it is
      considered to be a potential treatment for retinal degenerative disorders. Here
      we report that the suppression of ERG responses is attributable to negative
      regulation of the phototransduction machinery in rod photoreceptors. Intravitreal
      injection of recombinant human CNTF protein in rat results in a series of
      biochemical and morphological changes in rod photoreceptors. CNTF induces a
      decrease in rhodopsin expression and an increase in arrestin level.
      Morphologically, CNTF treatment causes a shortening of rod outer segments (ROS).
      All of these changes are fully reversible. The lower rhodopsin level and
      shortened ROS reduce the photon catch of rods. Less rhodopsin and more arrestin
      dramatically increase the arrestin-to-rhodopsin ratio so that more arrestin
      molecules are available to quench the photoexcited rhodopsin. The overall effect
      of CNTF is to negatively regulate the phototransduction machinery, which reduces
      the photoresponsiveness of rods, resulting in lower ERG amplitude at a given
      intensity of light stimulus. The CNTF-induced changes in rods are similar to
      those in light-induced photoreceptor plasticity. Whether CNTF-induced changes in
      rods are through the same mechanism that mediates light-induced photoreceptor
      plasticity remains to be answered.

PMID- 17192436
TI  - Single-cell characterization of retrograde signaling by brain-derived
      neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) is a key regulator of hippocampal
      synaptic plasticity in the developing and adult nervous system. It can be
      released from pyramidal neuron dendrites in an activity-dependent manner and has
      therefore been suggested to serve as a signal that provides the retrograde
      intercellular communication necessary for Hebbian plasticity and hippocampal
      dependent learning. Although much has been learned about BDNF function by field
      stimulation of hippocampal neurons, it is not known whether moderate action
      potential-independent depolarization of single cells is capable of releasing
      sufficient BDNF to influence transmission at individual synapses. In this study,
      we show directly at the single-cell level that such modulation can occur. By
      using K-252a, anti-BDNF antibody, and interruption of regulated release, we
      confirm a model in which postsynaptic depolarization elicits calcium-dependent
      release of BDNF that diffuses retrogradely and enhances presynaptic transmitter
      release.

PMID- 17192437
TI  - Luminance-evoked inhibition in primary visual cortex: a transient veto of
      simultaneous and ongoing response.
AB  - Large-scale changes in luminance are known to exert a significant suppressive or
      masking effect on visual perception, but the neural substrate for this effect
      remains unclear. In this report, we describe the results of experiments using in
      vivo intracellular recording to explore the impact of luminance transients on the
      responses of orientation-selective neurons in layer 2/3 of tree shrew primary
      visual cortex. By measuring changes in excitatory and inhibitory conductances, we
      find that instantaneous changes in luminance evoke strong cortical inhibition.
      When combined with visual stimuli that would otherwise yield strong excitatory
      responses, luminance transients produce significant reductions in excitation as
      well as increases in inhibition. As a result, luminance transients significantly
      delay the emergence of orientation tuned cortical responses, and virtually
      eliminate ongoing responses to effective stimuli. We conclude that cortical
      inhibition is a critical factor in luminance-evoked cortical suppression and the
      likely substrate for luminance-induced visual masking phenomenon.

PMID- 17192439
TI  - Extracellular hippocampal acetylcholine level controls amygdala function and
      promotes adaptive conditioned emotional response.
AB  - Ample data indicate that tone and contextual fear conditioning differentially
      require the amygdala and the hippocampus. However, mechanisms subserving the
      adaptive selection among environmental stimuli (discrete tone vs context) of
      those that best predict an aversive event are still elusive. Because the
      hippocampal cholinergic neurotransmission is thought to play a critical role in
      the coordination between different memory systems leading to the selection of
      appropriate behavioral strategies, we hypothesized that this cholinergic signal
      may control the competing acquisition of amygdala-mediated tone and contextual
      conditioning. Using pavlovian fear conditioning in mice, we first show a higher
      level of hippocampal acetylcholine release and a specific pattern of
      extracellular signal-regulated kinase 1/2 (ERK1/2) activation within the lateral
      (LA) and basolateral (BLA) amygdala under conditions in which the context is a
      better predictor than a discrete tone stimulus. Second, we demonstrate that
      levels of hippocampal cholinergic neurotransmission are causally related to the
      patterns of ERK1/2 activation in amygdala nuclei and actually determine the
      selection among the context or the simple tone the stimulus that best predicts
      the aversive event. Specifically, decreasing the hippocampal cholinergic signal
      not only impaired contextual conditioning but also mimicked conditioning to the
      discrete tone, both in terms of the behavioral outcome and the LA/BLA ERK1/2
      activation pattern. Conversely, increasing this cholinergic signal not only
      disrupted tone conditioning but also promoted contextual fear conditioning.
      Hence, these findings highlight that hippocampal cholinergic neurotransmission
      controls amygdala function, thereby leading to the selection of relevant
      emotional information.

PMID- 17192438
TI  - Forebrain adenosine A2A receptors contribute to L-3,4-dihydroxyphenylalanine
      induced dyskinesia in hemiparkinsonian mice.
AB  - Adenosine A2A receptor antagonists provide a promising nondopaminergic approach
      to the treatment of Parkinson's disease (PD). Initial clinical trials of A2A
      antagonists targeted PD patients who had already developed treatment
      complications known as L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia
      (LID) in an effort to improve symptoms while reducing existing LID. The goal of
      this study is to explore the effect of A2A antagonists and targeted A2A receptor
      depletion on the actual development of sensitized responses to L-DOPA in mouse
      models of LID in PD. Hemiparkinsonian mice (unilaterally lesioned with 6-OHDA)
      were treated daily for 3 weeks with a low dose of L-DOPA (2 mg/kg) preceded by a
      low dose of selective A2A antagonist (KW-6002 [(E)-1,3-diethyl-8-(3,4
      dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione] at 0.03 or 0.3 mg/kg,
      or SCH58261 [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4
      triazolo[1,5-c]pyrimidine] at 0.03 mg/kg) or vehicle intraperitoneally. In
      control mice, contralateral rotational responses to daily L-DOPA gradually
      increased over the initial week before reaching a persistent maximum. Both A2A
      antagonists inhibited the development of sensitized contralateral turning, with
      KW-6002 pretreatment reducing the sensitized rotational responses by up to
      threefold. The development of abnormal involuntary movements (a measure of LID)
      as well as rotational responses was attenuated by the postnatal depletion of
      forebrain A2A receptors in conditional (Cre/loxP system) knock-out mice. These
      pharmacological and genetic data provide evidence that striatal A2A receptors
      play an important role in the neuroplasticity underlying behavioral sensitization
      to L-DOPA, supporting consideration of early adjunctive therapy with an A2A
      antagonist to reduce the risk of LID in PD.

PMID- 17192440
TI  - Receptive field properties of the macaque second somatosensory cortex: nonlinear
      mechanisms underlying the representation of orientation within a finger pad.
AB  - We investigate the position invariant receptive field properties of neurons in
      the macaque second somatosensory (SII) cortical region. Previously we reported
      that many SII region neurons show orientation tuning in the center of multiple
      finger pads of the hand and further that the tuning is similar on different pads,
      which can be interpreted as position invariance. Here we study the receptive
      field properties of a single finger pad for a subset (n = 61) of those 928
      neurons, using a motorized oriented bar that we positioned at multiple locations
      across the pad. We calculate both vector fields and linear receptive fields of
      the finger pad to characterize the receptive field properties that give rise to
      the tuning, and we perform an additional regression analysis to quantify
      linearity, invariance, or both in individual neurons. We show that orientation
      tuning of SII region neurons is based on a variety of mechanisms. For some
      neurons, the tuning is explained by simple excitatory regions, simple inhibitory
      regions, or some combination of these structures. However, a large fraction of
      the neurons (n = 20 of 61, 33%) show position invariance that is not explained
      well by their linear receptive fields. Finding invariance within a finger pad,
      coupled with the previous result of similar tuning on different pads, indicates
      that some SII region neurons may exhibit similar tuning throughout large regions
      of the hand. We hypothesize that invariant neurons play an important role in
      tactile form recognition.

PMID- 17192442
TI  - Genetic toxicity assessment: employing the best science for human safety
      evaluation. Part II: Performances of the in vitro micronucleus test compared to
      the mouse lymphoma assay and the in vitro chromosome aberration assay.
AB  - The in vitro micronucleus test is commonly used in the early stages of
      pharmaceutical development as a predictive tool for the regulatory mouse lymphoma
      assay or in vitro chromosome aberration test. The accumulated data from this
      assay leads to the suggestion that it could be used as an alternative to the
      chromosome aberration test or the mouse lymphoma assay in the regulatory
      genotoxicity battery. In this paper, we present the results of the in vitro
      micronucleus test on L5178Y mouse lymphoma cells with 25 compounds from Servier
      research and have compared these results to those obtained in the genotoxicity
      regulatory battery. All the negative compounds were also negative in the in vitro
      micronucleus assay. Among the 14 positive compounds, two of them, positive in the
      mouse lymphoma assay, were found negative in the in vitro micronucleus test.
      However, this apparent discordance was likely to be due to cytotoxicity- or high
      concentration-related false positive responses in the mouse lymphoma assay. In
      addition, we confirmed that the in vitro micronucleus assay is useful for
      detecting aneugens, especially, when cells in metaphasis and multinucleated cells
      are also scored and when cells are allowed to recover after the long treatment.
      On this series of compounds, the in vitro micronucleus assay showed high
      sensitivity and possibly a better specificity than the mouse lymphoma assay.
      Thus, the in vitro micronucleus assay was shown to be at least as adequate as the
      mouse lymphoma assay or the in vitro chromosome aberration test to be used in the
      standard genotoxicity battery.

PMID- 17192441
TI  - Comet fluorescence in situ hybridization analysis for oxidative stress-induced
      DNA damage in colon cancer relevant genes.
AB  - Our objective was to study whether products of oxidative stress, such as hydrogen
      peroxide (H(2)O(2)), trans-2-hexenal, and 4-hydroxy-2-nonenal (HNE), cause DNA
      damage in genes, relevant for human colon cancer. For this, total DNA damage was
      measured in primary human colon cells and colon adenoma cells (LT97) using the
      single-cell gel electrophoresis assay, known as "Comet Assay." APC, KRAS, and
      TP53 were marked in the comet images using fluorescence in situ hybridization
      (Comet FISH). The migration of APC, KRAS, or TP53 signals into the comet tails
      was quantified and compared to total DNA damage. All three substances were
      clearly genotoxic for APC, KRAS, and TP53 genes and total DNA in both types of
      cells. In primary colon cells, TP53 gene was more sensitive toward H(2)O(2),
      trans-2-hexenal, and HNE than total DNA was. In LT97 cells, the TP53 gene was
      more sensitive only toward trans-2-hexenal and HNE. APC and KRAS genes were more
      susceptible than total DNA to both lipid peroxidation products but only in
      primary colon cells. This suggests genotoxic effects of lipid peroxidation
      products in APC, KRAS, and TP53 genes. In LT97 cells, TP53 was more susceptible
      than APC and KRAS toward HNE. Based on the reported gatekeeper properties of
      TP53, which in colon adenoma is frequently altered to yield carcinoma, this
      implies that HNE is likely to contribute to cancer progression. This new
      experimental approach facilitates studies on effects of nutrition-related
      carcinogens in relevant target genes.

PMID- 17192443
TI  - Need for standardized sign-out in the emergency department: a survey of emergency
      medicine residency and pediatric emergency medicine fellowship program directors.
AB  - OBJECTIVES: To determine the existing patterns of sign-out processes prevalent in
      emergency departments (EDs) nationwide. In addition, to assess whether training
      programs provide specific guidance to their trainees regarding sign-outs and
      attitudes of emergency medicine (EM) residency and pediatric EM fellowship
      program directors toward the need for the development of standardized guidelines
      relating to sign-outs. METHODS: A Web-based survey of training program directors
      of each Accreditation Council for Graduate Medical Education (ACGME)-accredited
      EM residency and pediatric EM fellowship program was conducted in March 2006.
      RESULTS: Overall, 185 (61.1%) program directors responded to the survey. One
      hundred thirty-six (73.5%) program directors reported that sign-outs at change of
      shift occurred in a common area within the ED, and 79 (42.7%) respondents
      indicated combined sign-outs in the presence of both attending and resident
      physicians. A majority of the programs, 119 (89.5%), stated that there was no
      uniform written policy regarding patient sign-out in their ED. Half (50.3%) of
      all those surveyed reported that physicians sign out patient details "verbally
      only," and 79 (42.9%) noted that transfer of attending responsibility was "rarely
      documented." Only 34 (25.6%) programs affirmed that they had formal didactic
      sessions focused on sign-outs. A majority (71.6%) of program directors surveyed
      agreed that specific practice parameters regarding transfer of care in the ED
      would improve patient care; 80 (72.3%) agreed that a standardized sign-out system
      in the ED would improve communication and reduce medical error. CONCLUSIONS:
      There is wide variation in the sign-out processes followed by different EDs. A
      majority of those surveyed expressed the need for standardized sign-out systems.

PMID- 17192444
TI  - International emergency medicine: a review of the literature.
AB  - The field of international emergency medicine has grown rapidly over the past
      several decades, with an increase in the number of interested individuals and in
      the range of topics included under its rubric. One of the greatest obstacles,
      however, faced by international emergency medicine researchers and practitioners
      alike remains the lack of a high-quality, consolidated, and easily accessible
      evidence base of literature. In response to this perceived need, members of the
      Emergency Medicine Residents' Association International Emergency Medicine
      Committee, in conjunction with members of the Society for Academic Emergency
      Medicine International Interest Group, embarked on the task of creating a
      recurring review of international emergency medicine literature. Articles for
      this first annual review, covering research published in 2005, were selected
      according to explicit, predetermined criteria that included both methodological
      quality and perceived impact of the research. It is our hope that this annual
      review will act as a forum for disseminating best practices, while also
      stimulating further research in the field of international emergency medicine.

PMID- 17192445
TI  - Anticipating demand for emergency health services due to medication-related
      adverse events after rapid mass prophylaxis campaigns.
AB  - OBJECTIVES: Mass prophylaxis against infectious disease outbreaks carries the
      risk of medication-related adverse events (MRAEs). The authors sought to define
      the relationship between the rapidity of mass prophylaxis dispensing and the
      subsequent demand for emergency health services due to predictable MRAEs.
      METHODS: The authors created a spreadsheet-based computer model that calculates
      scenario-specific predicted daily MRAE rates from user inputs by applying a
      probability distribution to the reported timing of MRAEs. A hypothetical two- to
      ten-day prophylaxis campaign for one million people using recent data from both
      smallpox vaccination and anthrax chemoprophylaxis campaigns was modeled. RESULTS:
      The length of a mass prophylaxis campaign plays an important role in determining
      the subsequent intensity in emergency services utilization due to real or
      suspected adverse events. A two-day smallpox vaccination scenario would produce
      an estimated 32,000 medical encounters and 1,960 hospitalizations, peaking at
      5,246 health care encounters six days after the start of the campaign; in
      contrast, a ten-day campaign would lead to 41% lower peak surge, with a maximum
      of 3,106 encounters on the busiest day, ten days after initiation of the
      campaign. MRAEs with longer lead times, such as those associated with anthrax
      chemoprophylaxis, exhibit less variability based on campaign length (e.g., 124
      out of an estimated 1,400 hospitalizations on day 20 after a two-day campaign
      versus 103 on day 24 after a ten-day campaign). CONCLUSIONS: The duration of a
      mass prophylaxis campaign may have a substantial impact on the timing and peak
      number of clinically significant MRAEs, with very short campaigns overwhelming
      existing emergency department (ED) capacity to treat real or suspected medication
      related injuries. While better reporting of both incidence and timing of MRAEs in
      future prophylaxis campaigns should improve the application of this model to
      community-based emergency preparedness planning, these results highlight the need
      for coordination between public health and emergency medicine planning for
      infectious disease outbreaks to avoid preventable surges in ED utilization.

PMID- 17192446
TI  - Commentary: The affective imperative: coming to terms with our emotions.

PMID- 17192448
TI  - The national trend in quality of emergency department pain management for long
      bone fractures.
AB  - BACKGROUND: Despite national attention, there is little evidence that the quality
      of emergency department (ED) pain management is improving. OBJECTIVES: To compare
      the quality of ED pain management before and after implementation of the Joint
      Commission on the Accreditation of Healthcare Organizations' standards in 2001.
      METHODS: The authors performed a retrospective cohort study by using the National
      Hospital Ambulatory Medical Care Survey from 1998-2003. Patients who presented to
      the ED with a long bone fracture (femur, humerus, tibia, fibula, radius, or ulna)
      were compared. The authors extracted data on patient, visit, and hospital
      characteristics. The primary outcomes were the proportion of patients who
      received assessment of pain severity and who received analgesic treatment.
      RESULTS: There were 2,064 patients with a qualifying fracture in the study
      period, 834 from 1998-2000 and 1,230 from 2001-2003. Compared with the early
      period, a higher proportion of patients in the late period had their pain
      assessed (74% vs. 57%), received opiates (56% vs. 50%), and received any
      analgesic (76% vs. 56%). Patients in the late period had higher odds of receiving
      any analgesia (adjusted odds ratio [OR], 1.43) and opioid analgesia (adjusted OR,
      1.27) compared with the early period. Patients in the middle age group (adjusted
      OR, 2.28) or those seen by physician assistants (adjusted OR, 2.05) were more
      likely, whereas those with Medicaid (adjusted OR, 0.58) and those in the
      Northeast were less likely, to receive opiates. CONCLUSIONS: Although the quality
      of ED pain management for acute fractures appears to be improving, there is still
      room for further improvement.

PMID- 17192449
TI  - Atypical clinical features of pediatric appendicitis.
AB  - BACKGROUND: The diagnosis of appendicitis remains challenging in children. Delays
      in diagnosis, or misdiagnosis, have important medical and legal implications. The
      typical, or classic, presentation of pediatric appendicitis has been modeled
      after adult disease; however, many children present atypically with subtle
      findings or unusual signs. OBJECTIVES: To determine the frequency of atypical
      clinical features among pediatric patients with appendicitis and to investigate
      which atypical features are the strongest negative predictors for appendicitis
      among patients being evaluated for appendicitis. METHODS: Children and
      adolescents with suspected appendicitis were enrolled over 20 consecutive months.
      Pediatric emergency physicians completed standardized data collection forms on
      eligible patients. Final diagnosis was determined by pathology or follow-up
      telephone call. Typical and atypical findings were defined strictly a priori.
      RESULTS: Seven hundred fifty-five patients were enrolled. The median age was 11.9
      years (interquartile range [IQR]: 8.5, 14.9 yr); 36% of patients were diagnosed
      with appendicitis. Among patients with appendicitis, the most common atypical
      features included absence of pyrexia (83%), absence of Rovsing's sign (68%),
      normal or increased bowel sounds (64%), absence of rebound pain (52%), lack of
      migration of pain (50%), lack of guarding (47%), abrupt onset of pain (45%), lack
      of anorexia (40%), absence of maximal pain in the right lower quadrant (32%), and
      absence of percussive tenderness (31%). Forty-four percent of patients with
      proven appendicitis had six or more atypical characteristics. The median number
      of atypical features for patients with proven appendicitis was five (IQR: 4.0,
      7.0). The greatest negative predictors, on the basis of likelihood ratios, were
      as follows: white blood cell count (WBC) of <10,000 per cubic millimeter
      (likelihood ratios [LR], 0.18), absolute neutrophil count (ANC) of <7,500 per
      cubic millimeter (LR, 0.35), lack of percussive tenderness (LR, 0.50), lack of
      guarding (LR, 0.63), and no nausea or emesis (LR, 0.65). CONCLUSIONS:
      Appendicitis in pediatric patients is difficult to diagnose because children
      present with a wide variety of atypical clinical features. Forty-four percent of
      patients with appendicitis presented with six or more atypical features. Two
      atypical features are the strongest negative predictors of appendicitis in
      children: WBC of <10,000 per cubic millimeter and an ANC of <7,500 per cubic
      millimeter.

PMID- 17192450
TI  - Routine versus selective abdominal computed tomography scan in the evaluation of
      right lower quadrant pain: a randomized controlled trial.
AB  - OBJECTIVES: To determine the role of abdominal computed tomography (CT) imaging
      in patients with right lower quadrant (RLQ) pain. The authors hypothesized that
      selective use of abdominal CT would reduce imaging without increasing the rates
      of negative appendectomy and perforated appendicitis. METHODS: A prospective
      randomized clinical trial was conducted in a community teaching emergency
      department. Adult patients with acute RLQ abdominal pain with suspected acute
      appendicitis were included. Patients were randomized to mandatory (all patients)
      or selective (based on clinical evaluation) abdominal CT imaging. The primary
      outcome was the negative appendectomy rate. RESULTS: A total of 152 patients were
      randomized to selective (n = 80) and mandatory (n = 72) intervention groups. The
      mean (+/-SD) age was 34.1 (+/-3.5) years, and 48% were female. CT imaging was
      performed in 54 of 80 patients (68%; 95% confidence interval [CI] = 56% to 78%)
      in the selective group and in 70 of 72 patients (97%; 95% CI = 90% to 100%) in
      the mandatory group. There was a trend to a decreased rate of negative
      appendectomy in the mandatory group (1/39 [2.6%]; 95% CI = 0.5% to 13.2%) as
      compared with the selective group (6/43 [13.9%]; 95% CI = 6.6% to 27.3%), with a
      difference in prevalence rates of 11.3% (95% CI = -3.5% to 26.3%). There was also
      a trend to a decreased perforated appendix rate in the mandatory group (4/39
      [10.3%]) as compared with the selective group (7/38 [18.4%]), with a difference
      in prevalence rates of 8.2% (95% CI = -8.0% to 24.4%). CONCLUSIONS: In this small
      sample of adult patients with RLQ abdominal pain and suspected acute
      appendicitis, CT imaging was performed less frequently in the selective group and
      there was a trend with mandatory CT imaging to reduced rates of negative
      appendectomy and perforated appendices.

PMID- 17192451
TI  - Trichotillomania and trichobezoar: a clinical practice insight with report of
      illustrative case.
AB  - Untreated trichophagia secondary to trichotillomania is a potentially life
      threatening condition. Taking a thorough family and social history, most notably
      with the aid of a genogram or family tree, can aid in including this disorder in
      the differential diagnosis. This case presentation describes a unique occurrence
      of untreated trichotillomania in a female adolescent that led to formation of a
      trichobezoar requiring emergent surgical intervention and follow-up psychiatric
      treatment. This case highlights osteopathic medicine's fundamental concept of
      treating the whole person rather than just symptoms by considering factors such
      as genetic influences in understanding disease.

PMID- 17192452
TI  - Prednisone-induced osteoporosis: an overlooked and undertreated adverse effect.
AB  - CONTEXT: Glucocorticoids are used for a variety of medical conditions. This class
      of drugs is arguably the most common cause of iatrogenic osteoporosis, but
      studies have shown that physicians are not investigating and treating
      glucocorticoid-induced osteoporosis. OBJECTIVE: To determine whether primary care
      physicians (osteopathic and allopathic) are evaluating and treating adult
      patients at risk for osteoporosis secondary to long-term prednisone use. METHODS:
      Electronic medical records from three primary care practices (family medicine,
      geriatric medicine, and internal medicine) were retrospectively reviewed to
      identify patients who were taking at least 2.5 mg of prednisone per day for 8
      weeks or longer. Records were then grouped according to whether patients had
      undergone bone mineral density screening and had been given therapy to prevent or
      treat bone loss. Whether patients had comorbid risk factors for secondary
      osteoporosis (according to the National Institutes of Health Consensus
      Development Conference Statement on Osteoporosis) was noted to determine whether
      treatment was given because of prednisone use or because of the comorbid risk
      factors. Statistical analysis was performed using a Pearson product moment
      correlation 2-tailed chi2 test. RESULTS: The medical records of 49 patients met
      inclusion criteria (19 men, 30 women; mean age, 61 years; age range, 21-89
      years). A statistically significant difference was found in physician evaluation
      practices for patients with vs patients without comorbid risk factors (82.1% vs
      38.1%; P=.002). CONCLUSION: Primary care physicians do not routinely evaluate
      patients for osteoporosis secondary to glucocorticoid treatment, especially when
      patients do not have comorbid risk factors for osteoporosis.

PMID- 17192453
TI  - Teaching critical appraisal: a pilot randomized controlled outcomes trial in
      undergraduate osteopathic medical education.
AB  - CONTEXT: Critical appraisal is an important skill for medical students. A
      proposed curriculum may be an effective teaching tool. OBJECTIVE: To determine
      whether the teaching of critical appraisal can be successfully introduced into an
      osteopathic clinical clerkship in obstetrics and gynecology. DESIGN: Osteopathic
      medical students (N=77) were assigned by lottery to one of eight rotation groups
      during their clinical clerkship in obstetrics and gynecology. Four of these
      rotation groups received instruction in critical appraisal (study group; received
      evidence-based medicine [EBM] curriculum; n=38); the other four rotation groups
      did not (control group; received non-EBM; n=39). The ability of the study EBM
      group to critically analyze the literature was compared with that of the control
      (non-EBM) group on the basis of results of a multiple-choice examination.
      SETTING: The University of Medicine and Dentistry of New Jersey-School of
      Osteopathic Medicine clinical clerkship in obstetrics and gynecology. RESULTS:
      The median scores for critical analysis were 41 for the control group and 64 for
      the study group. This difference was statistically significant (P<.001).
      CONCLUSION: The teaching of critical appraisal can be successfully introduced
      into a clerkship in obstetrics and gynecology.

PMID- 17192454
TI  - Multiple aortocoronary bypass saphenous vein graft aneurysms in a 77-year-old
      man.
AB  - Aneurysms of aortocoronary saphenous vein bypass grafts are a rare complication
      of coronary artery bypass grafts. The authors report the incidental finding of
      four aneurysms in two aortocoronary saphenous vein bypass grafts in a 77-year-old
      man with progressive generalized weakness, left facial drooping, and digitalis
      toxicity. A brief review of the literature on this rare condition is also
      provided.

PMID- 17192455
TI  - Interests in research electives among osteopathic medical students.
AB  - CONTEXT: The number of physician-researchers in the United States is in decline.
      Osteopathic medical schools must examine strategies for increasing the number of
      trained clinical researchers. OBJECTIVES: To assess the interest of first- and
      second-year osteopathic medical students in taking an elective research course
      during their third and fourth years of medical school; and to examine the
      relationship among students' personal characteristics, previous research
      experience, and elective research courses. DESIGN: Fifteen-question, self
      administered, cross-sectional survey. SETTING: Edward Via Virginia College of
      Osteopathic Medicine in Blacksburg in September 2004. PARTICIPANTS: First- and
      second-year osteopathic medical students. MAIN OUTCOME MEASURES: Personal
      characteristics, previous research experience, and research elective interest (8
      week vs 12-week course; and clinical/population vs basic science focus). RESULTS:
      The response rate was 83.9% (N=255 [149 first-year students; 106 second-year
      students]), with 51% women responding. Approximately 72% of students had worked
      on a research project at some time during undergraduate or medical training, and
      42% had completed an undergraduate, data-based thesis. Students reported greater
      interest in a 12-week elective (34%) than an 8-week elective (23%), and two
      thirds preferred a clinical and/or population to a basic science focus.
      CONCLUSIONS: Colleges of osteopathic medicine must develop research training and
      mentoring programs to foster such interests in their students, and innovative
      recruitment approaches need to be developed for DO/PhD degree programs. These
      strategies will help provide meaningful research education and experiences to
      osteopathic medical students.

PMID- 17192459
TI  - Liraglutide, a long-acting glucagon-like peptide-1 analog, reduces body weight
      and food intake in obese candy-fed rats, whereas a dipeptidyl peptidase-IV
      inhibitor, vildagliptin, does not.
AB  - Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the
      dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese
      by supplementary candy feeding. Female Sprague-Dawley rats were randomized to 12
      week diets of chow or chow plus candy. The latter were randomized for 12 further
      weeks to continue their diet while receiving 0.2 mg/kg liraglutide twice daily
      subcutaneously, 10 mg/kg vildagliptin twice daily orally, or vehicle or to revert
      to chow-only diet. Energy expenditure was measured, and oral glucose tolerance
      tests (OGTTs) were performed. Body composition was determined by dual-energy X
      ray absorptiometry scanning, and pancreatic beta-cell mass was determined by
      histology. Candy feeding increased weight, fat mass, and feeding-associated
      energy expenditure. Liraglutide or reversal to chow diet fully reversed weight
      and fat gains. Liraglutide was associated with decreased calorie intake and
      shifted food preference (increased chow/decreased candy consumption). Despite
      weight loss, liraglutide-treated rats did not decrease energy expenditure
      compared with candy-fed controls. Vildagliptin affected neither weight, food
      intake, nor energy expenditure. OGTTs, histology, and blood analyses indirectly
      suggested that both drugs increased insulin sensitivity. Liraglutide and
      vildagliptin inhibited obesity-associated increases in beta-cell mass. This was
      associated with weight and fat mass normalization with liraglutide, but not
      vildagliptin, where the ratio of beta-cell to body mass was low.

PMID- 17192460
TI  - Increased inflammatory properties of adipose tissue macrophages recruited during
      diet-induced obesity.
AB  - Although recent studies show that adipose tissue macrophages (ATMs) participate
      in the inflammatory changes in obesity and contribute to insulin resistance, the
      properties of these cells are not well understood. We hypothesized that ATMs
      recruited to adipose tissue during a high-fat diet have unique inflammatory
      properties compared with resident tissue ATMs. Using a dye (PKH26) to pulse label
      ATMs in vivo, we purified macrophages recruited to white adipose tissue during a
      high-fat diet. Comparison of gene expression in recruited and resident ATMs using
      real-time RT-PCR and cDNA microarrays showed that recruited ATMs overexpress
      genes important in macrophage migration and phagocytosis, including interleukin-6
      (IL-6), inducible nitric oxide synthase (iNOS), and C-C chemokine receptor 2
      (CCR2). Many of these genes were not induced in ATMs from high-fat diet-fed CCR2
      knockout mice, supporting the importance of CCR2 in regulating recruitment of
      inflammatory ATMs during obesity. Additionally, expression of Apoe was decreased,
      whereas genes important in lipid metabolism, such as Pparg, Adfp, Srepf1, and
      Apob48r, were increased in the recruited macrophages. In agreement with this,
      ATMs from obese mice had increased lipid content compared with those from lean
      mice. These studies demonstrate that recruited ATMs in obese animals represent a
      subclass of macrophages with unique properties.

PMID- 17192461
TI  - Involvement of apolipoprotein E in excess fat accumulation and insulin
      resistance.
AB  - Although apolipoprotein E (apoE) is well known to play a major role in lipid
      metabolism, its role in glucose and energy homeostasis remains unclear. Herein,
      we established apoE-deficient genetically obese Ay (apoE(-/-);Ay/+) mice. ApoE
      deficiency in Ay mice prevented the development of obesity, with decreased fat
      accumulation in the liver and adipose tissues. ApoE(-/-);Ay/+ mice exhibited
      better glucose tolerance than apoE(+/+);Ay/+ mice. Insulin tolerance testing and
      hyperinsulinemic-euglycemic clamp study revealed marked improvement of insulin
      sensitivity, despite increased plasma free fatty acid levels. These metabolic
      phenotypes were reversed by adenoviral replenishment of apoE protein, indicating
      circulating apoE to be involved in increased adiposity and obesity-related
      metabolic disorders. Uptake of apoE-lacking VLDL into the liver and adipocytes
      was markedly inhibited, but adipocytes in apoE(-/-);Ay/+ mice exhibited normal
      differentiation, suggesting that apoE-dependent VLDL transport is involved in the
      development of obesity, i.e., surplus fat accumulation. Interestingly, apoE(-/
      );Ay/+ mice exhibited decreased food intake and increased energy expenditure.
      Pair-feeding experiments indicate these phenomena to both contribute to the
      obesity-resistant phenotypes associated with apoE deficiency. Thus, apoE is
      involved in maintaining energy homeostasis. ApoE-dependent excess fat
      accumulation is a promising therapeutic target for the metabolic syndrome.

PMID- 17192462
TI  - RegII is a beta-cell protein and autoantigen in diabetes of NOD mice.
AB  - The Reg family of proteins has been studied in the context of growth and
      regeneration in several organs including pancreatic islets. We previously
      suggested that Reg proteins act as autoantigens in type 1 diabetes, based on
      evidence that a member of the Reg family (hepatocellular carcinoma intestine
      pancreas [HIP]/pancreatitis-associated protein [PAP]) was overexpressed in the
      islets of a patient who died after sudden onset of type 1 diabetes, and that, in
      NOD mice, Reg-specific T-cells adoptively transferred diabetes. In the current
      study, we developed antisera to detect individual Reg members in mouse islets and
      found that RegIIIalpha was present in the non-beta-cell portion of the islets,
      while RegII was predominantly expressed in beta-cells. Vaccination of NOD mice
      with the separately expressed N-terminal (NtfrII) or C-terminal (CtfrII) portion
      of RegII revealed a dichotomy: NtfrII vaccination accelerated and CtfrII
      vaccination delayed type 1 diabetes. Vaccination with CtfrII was more effective
      when given at later stages in the pathogenesis of type 1 diabetes, a time
      dependency different from that seen with other antigen-dependent vaccine
      strategies in NOD mice, which might have therapeutic implications. In conclusion,
      RegII is a novel beta-cell-derived autoantigen in NOD mice. The autoimmune
      response against this protein may convert a regenerative into an islet
      destructive process accelerating development of type 1 diabetes.

PMID- 17192463
TI  - Crystal structure of the major diabetes autoantigen insulinoma-associated protein
      2 reveals distinctive immune epitopes.
AB  - Insulinoma-associated protein-2 (IA-2) is a major autoantigen in type 1 diabetes
      that occurs through autoimmune-mediated beta-cell destruction. We present here
      the crystal structure of the protein tyrosine phosphatase (PTP)-like domain of
      human IA-2. The structure reveals a canonical PTP domain with the closed WPD loop
      over the active site pocket, explaining the lack of enzyme activity in the native
      protein. The structural interpretation of previous mutagenesis studies indicates
      that the B-cell epitopes are concentrated on two distinctive regions on
      peripheral loops of the central beta-sheet surrounding T-cell epitopes within the
      sheet. The detailed structural information on immune epitopes provides a
      framework for the future development of immune intervention strategies against
      diabetes.

PMID- 17192464
TI  - TIMP-1 transgenic mice recover from diabetes induced by multiple low-dose
      streptozotocin.
AB  - Type 1 diabetes results from autoimmune destruction of the insulin-producing beta
      cells of pancreatic islets, of which the capacity for self-replication in the
      adult is too limited to restore following extensive tissue injury. Tissue
      inhibitor of metalloproteinase (TIMP)-1 inhibits matrix metalloproteinase
      activity and regulates proliferation and apoptosis of a variety of cells types,
      depending on the context. Here, we show that overexpression of human TIMP-1 in
      pancreatic beta-cells of transgenic mice counteracts the cytotoxicity and
      insulitis induced by multiple low-dose streptozotocin (MLDS). Nontransgenic mice
      developed severe hyperglycemia, hypoinsulinemia, and insulitis 2 weeks after
      streptozotocin administration and died within 17 weeks. However, MLDS-treated
      transgenic mice gradually normalized the metabolic parameters and survived. beta
      Cell mass increased in parallel as a result of enhancement of beta-cell
      replication. Thus, our results have demonstrated for the first time that
      overexpression of TIMP-1 in beta-cells enhances the replication of pancreatic
      islets beta-cells and counteracts type 1 diabetes, indicating that the TIMP-1
      gene may be a potential target to prevent, or even reverse, type 1 diabetes.

PMID- 17192465
TI  - Tissue-specific deletion of the retinoblastoma protein in the pancreatic beta
      cell has limited effects on beta-cell replication, mass, and function.
AB  - Animal studies show that G(1/S) regulatory molecules (D-cyclins, cdk-4, p18, p21,
      p27) are critical for normal regulation of beta-cell proliferation, mass, and
      function. The retinoblastoma protein, pRb, is positioned at the very end of a
      cascade of these regulatory proteins and is considered the final checkpoint
      molecule that maintains beta-cell cycle arrest. Logically, removal of pRb from
      the beta-cell should result in unrestrained beta-cell replication, increased beta
      cell mass, and insulin-mediated hypoglycemia. Because global loss of both pRb
      alleles is embryonic lethal, this hypothesis has not been tested in beta-cells.
      We developed two types of conditional knockout (CKO) mice in which both alleles
      of the pRb gene were inactivated specifically in beta-cells. Surprisingly,
      although the pRb gene was efficiently recombined in beta-cells of both CKO
      models, changes in beta-cell mass, beta-cell replication rates, insulin
      concentrations, and blood glucose levels were limited or absent. Other pRb family
      members, p107 and p130, were not substantially upregulated. In contrast to dogma,
      the pRb protein is not essential to maintain cell cycle arrest in the pancreatic
      beta-cell. This may reflect fundamental inaccuracies in models of beta-cell cycle
      control or complementation for pRb by undefined proteins.

PMID- 17192466
TI  - Human islet amyloid polypeptide oligomers disrupt cell coupling, induce
      apoptosis, and impair insulin secretion in isolated human islets.
AB  - Insulin secretion from the 2,000-3,000 beta-cells in an islet is a highly
      synchronized activity with discharge of insulin in coordinate secretory bursts at
      approximately 4-min intervals. Insulin secretion progressively declines in type 2
      diabetes and following islet transplantation. Both are characterized by the
      presence of islet amyloid derived from islet amyloid polypeptide (IAPP). In the
      present studies, we examined the action of extracellular human IAPP (h-IAPP) on
      morphology and function of human islets. Because oligomers of h-IAPP are known to
      cause membrane disruption, we questioned if application of h-IAPP oligomers to
      human islets would lead to disruption of islet architecture (specifically cell-to
      cell adherence) and a decrease in coordinate function (e.g., increased entropy of
      insulin secretion and diminished coordinate secretory bursts). Both hypotheses
      are affirmed, leading to a novel hypothesis for impaired insulin secretion in
      type 2 diabetes and following islet transplantation, specifically disrupted cell
      to-cell adherence in islets through the actions of membrane-disrupting IAPP
      oligomers.

PMID- 17192467
TI  - Induction of indoleamine 2,3-dioxygenase by interferon-gamma in human islets.
AB  - Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial, rate-limiting step of
      tryptophan (Trp) catabolism along the kynurenine (KYN) pathway, and its induction
      in cells of the immune system in response to cytokines has been implicated in the
      regulation of antigen presentation and responses to cell-mediated immune attack.
      Microarray and quantitative PCR analyses of isolated human islets incubated with
      interferon (IFN)-gamma for 24 h revealed increased expression of IDO mRNA (>139
      fold) and Trp-tRNA synthase (WARS) (>17-fold) along with 975 other transcripts
      more than threefold, notably the downstream effectors janus kinase (JAK)2, signal
      transducer and activator of transcription (STAT)1, IFN-gamma regulatory factor-1,
      and several chemokines (CXCL9/MIG, CXCL10/IP10, CXCL11/1-TAC, CCL2, and
      CCL5/RANTES) and their receptors. IDO protein expression was upregulated in IFN
      gamma-treated islets and accompanied by increased intracellular IDO enzyme
      activity and the release of KYN into the media. The response to IFN-gamma was
      countered by interleukin-4 and 1alpha-methyl Trp. Immunohistochemical
      localization showed IDO to be induced in cells of both endocrine, including
      pancreatic duodenal homeobox 1-positive beta-cells, and nonendocrine origin. We
      postulate that in the short term, IDO activation may protect islets from
      cytotoxic damage, although chronic exposure to various Trp metabolites could
      equally lead to beta-cell attrition.

PMID- 17192468
TI  - Pro-survival role of gelsolin in mouse beta-cells.
AB  - We have previously shown that the Ca(2+)-dependent actin-severing protein
      gelsolin plays an important role in regulated insulin secretion. The aim of this
      study was to determine the role of gelsolin in beta-cell survival as it has been
      shown to play a dual role in apoptosis in other cell types. MIN6 subclones B1 and
      C3, shown previously to express gelsolin at different levels (B1>>C3 cells), were
      used for this purpose. We demonstrate that B1 cells have lower levels of
      apoptosis and active caspase-3 when compared with C3 cells, in both standard (25
      mmol/l glucose and 15% FCS) and deprived (5 mmol/l glucose and 1% FCS)
      conditions. Overexpression of gelsolin resulted in a decrease in the percentage
      of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      (TUNEL)(+) and active caspase-3(+) cells. Conversely, knockdown of gelsolin by
      RNA interference in B1 cells caused an increase in the number of TUNEL(+) and
      active caspase-3(+) cells. Finally, the anti-apoptotic role of gelsolin was
      confirmed in purified primary mouse beta-cells where overexpression of gelsolin
      resulted in a decrease in the percentage of TUNEL(+) cells. In summary, our
      results show for the first time that gelsolin plays a pro-survival role in
      pancreatic beta-cells.

PMID- 17192469
TI  - Peroxisome proliferator-activated receptor-gamma regulates expression of PDX-1
      and NKX6.1 in INS-1 cells.
AB  - In the 60% pancreatectomy (Px) rat model of beta-cell adaptation, normoglycemia
      is maintained by an initial week of beta-cell hyperplasia that ceases and is
      followed by enhanced beta-cell function. It is unknown how this complex series of
      events is regulated. We studied isolated islets and pancreas sections from 14-day
      post-Px versus sham-operated rats and observed a doubling of beta-cell nuclear
      peroxisome proliferator-activated receptor (PPAR)-gamma protein, along with a 2
      fold increase in nuclear pancreatic duodenal homeobox (Pdx)-1 protein and a 1.4
      fold increase in beta-cell nuclear Nkx6.1 immunostaining. As PPAR-gamma
      activation is known to both lower proliferation and have prodifferentiation
      effects in many tissues, we studied PPAR-gamma actions in INS-1 cells. A 3-day
      incubation with the PPAR-gamma agonist troglitazone reduced proliferation and
      increased Pdx-1 and Nkx6.1 immunostaining, along with glucokinase and GLUT2.
      Also, a 75% knockdown of PPAR-gamma using RNA interference lowered the mRNA
      levels of Pdx-1, glucokinase, GLUT2, and proinsulin II by more than half. Our
      results show a dual effect of PPAR-gamma in INS-1 cells: to curtail proliferation
      and promote maturation, the latter via enhanced expression of Pdx-1 and Nkx6.1.
      Additional studies are needed to determine whether there is a regulatory role for
      PPAR-gamma signaling in the beta-cell adaptation following a 60% Px in rats.

PMID- 17192470
TI  - FGFR3 is a negative regulator of the expansion of pancreatic epithelial cells.
AB  - Fibroblast growth factors (FGFs) and their receptors (FGFRs) are key signaling
      molecules for pancreas development. Although FGFR3 is a crucial developmental
      gene, acting as a negative regulator of bone formation, its participation remains
      unexplored in pancreatic organogenesis. We found that FGFR3 was expressed in the
      epithelia in both mouse embryonic and adult regenerating pancreata but was absent
      in normal adult islets. In FGFR3 knockout mice, we observed an increase in the
      proliferation of epithelial cells in neonates, leading to a marked increase in
      islet areas in adults. In vitro studies showed that FGF9 is a very potent ligand
      for FGFR3 and activates extracellular signal-related kinases (ERKs) in pancreatic
      cell lines. Moreover, FGFR3 blockade or FGFR3 deficiency led to increased
      proliferation of pancreatic epithelial cells in vivo. This was accompanied by an
      increase in the proportion of potential islet progenitor cells. Thus, our results
      show that FGFR3 signaling inhibits the expansion of the immature pancreatic
      epithelium. Consequently, this study suggests that FGFR3 participates in
      regulating pancreatic growth during the emergence of mature islet cells.

PMID- 17192471
TI  - Vascular reactivity in arterioles from normal and alloxan-diabetic mice: studies
      on single perfused islets.
AB  - Pancreatic islets possess an autonomous mechanism of blood flow regulation,
      independent of that of the exocrine pancreas. To study islet vascular regulation
      without confounding effects of the exocrine blood vessels, we have developed a
      technique enabling us to isolate single pancreatic islets and then to perfuse
      them using their endogenous vasculature for distribution of the medium. This made
      it possible to directly study the vascular reactivity of islet arterioles to
      different substances. We confirmed that control of islet blood flow is mainly
      located at the precapillary level. As expected, administration of angiotensin II
      and l-nitro-arginine methyl ester contracted islet arterioles, whereas nitric
      oxide and adenosine dilated them. d-glucose, the main insulin secretagogue, had a
      selective dilating effect on smooth muscle in islet arterioles but not in
      glomerular afferent arterioles. The response to glucose was amplified in islet
      arterioles from diabetic animals, indicating enhanced islet blood perfusion in
      diabetes. This newly developed technique for perfusing isolated pancreatic islets
      will provide new insights into islet perfusion control and its possible
      contributions to the pathogenesis of type 2 diabetes.

PMID- 17192472
TI  - Glucose-stimulated insulin production in mice deficient for the PAS kinase
      PASKIN.
AB  - The Per-ARNT-Sim (PAS) domain serine/threonine kinase PASKIN, or PAS kinase,
      links energy flux and protein synthesis in yeast and regulates glycogen synthase
      in mammals. A recent report suggested that PASKIN mRNA, protein, and kinase
      activity are increased in pancreatic islet beta-cells under hyperglycemic
      conditions and that PASKIN is necessary for insulin gene expression. We
      previously generated Paskin knockout mice by targeted replacement of the kinase
      domain with the beta-geo fusion gene encoding beta-galactosidase reporter
      activity. Here we show that no 5-bromo-4-chloro-3-indolyl-ss-d-galactopyranoside
      (X-gal) staining was observed in islet beta-cells derived from Paskin knockout
      mice, irrespective of the ambient glucose concentration, whereas adenoviral
      expression of the lacZ gene in beta-cells showed strong X-gal staining. No
      induction of PASKIN mRNA could be detected in insulinoma cell lines or in islet
      beta-cells. Increasing glucose concentrations resulted in PASKIN-independent
      induction of insulin mRNA levels and insulin release. PASKIN mRNA levels were
      high in testes but undetectable in pancreas and in islet beta-cells. Finally,
      blood glucose levels and glucose tolerance after intraperitoneal glucose
      injection were indistinguishable between Paskin wild-type and knockout mice.
      These results suggest that Paskin gene expression is not induced by glucose in
      pancreatic beta-cells and that glucose-stimulated insulin production is
      independent of PASKIN.

PMID- 17192473
TI  - Attenuation of angiotensin II signaling recouples eNOS and inhibits
      nonendothelial NOX activity in diabetic mice.
AB  - Angiotensin II (Ang II) levels are increased in patients with diabetes, but
      mechanisms underlying its contribution to diabetic vascular diseases are
      incompletely understood. We recently reported that in aortic endothelial cells,
      Ang II induces endothelial nitric oxide synthase (eNOS) uncoupling to produce
      superoxide (O(2)*(-)) rather than nitric oxide (NO*), upon loss of the
      tetrahydrobiopterin (H(4)B) salvage enzyme dihydrofolate reductase (DHFR). Here,
      we found that streptozotocin-induced diabetic mice had a marked increase in
      aortic O(2)*(-) production, which was inhibited by N-nitro-l-arginine methyl
      ester hydrochloride, indicating uncoupling of eNOS. Ang II receptor type 1
      blocker candesartan or ACE inhibitor captopril markedly attenuated eNOS-derived
      O(2)*(-) and hydrogen peroxide production while augmenting NO* bioavailability in
      diabetic aortas, implicating recoupling of eNOS. O(2)*(-) and NO* production were
      characteristically and quantitatively measured by electron spin resonance. DHFR
      expression was decreased in diabetic aortas but significantly restored by
      candesartan or captopril. Either also improved vascular H(4)B content and
      endothelium-dependent vasorelaxation in diabetes. Rac1-dependent NAD(P)H oxidase
      (NOX) activity was more than doubled in the endothelium-denuded diabetic aortas
      but was attenuated by candesartan or captopril, indicating that NOX remains
      active in nonendothelial vascular tissues, although uncoupled eNOS is responsible
      for endothelial production of O(2)*(-). These data demonstrate a novel role of
      Ang II in diabetic uncoupling of eNOS and that Ang II-targeted therapy improves
      endothelial function via the novel mechanism of recoupling eNOS. Dual
      effectiveness on uncoupled eNOS and NOX may explain the high efficacy of Ang II
      antagonists in restoring endothelial function.

PMID- 17192474
TI  - Diabetes abolishes morphine-induced cardioprotection via multiple pathways
      upstream of glycogen synthase kinase-3beta.
AB  - The cardioprotective effect of opioids or glycogen synthase kinase (GSK)
      inhibitors given at reperfusion has not been investigated in diabetes models.
      Therefore, nondiabetic (NDBR) or streptozotocin-induced diabetic (DBR) rat hearts
      were subjected to 30 min of ischemia and 2 h of reperfusion. Groups of NDBR or
      DBR were administered either vehicle, morphine (0.3 mg/kg), or the GSK inhibitor
      SB216763 (0.6 mg/kg) 5 min before reperfusion. SB216763 (but not morphine)
      reduced infarct size in DBRs (44 +/- 1* and 55 +/- 2%, respectively), while both
      agents reduced infarct size in NDBRs versus untreated NDBRs or DBRs (44 +/- 3*,
      42 +/- 3*, 60 +/- 2, and 56 +/- 2%, respectively, *P < 0.001). Morphine-induced
      phospho- (P-)GSK3beta was reduced 5 min after reperfusion in DBRs compared with
      NDBRs (0.83 +/- 0.29 and 1.94 +/- 0.12 [P < 0.05] pg/microg tissue,
      respectively). The GSK3beta mediators, P-Akt, P-extracellular signal-related
      kinase (ERK)1, and P-signal transducer and activator of transcription (STAT)3,
      were also significantly reduced in untreated DBR compared with NDBR rats.
      Morphine-induced elevations of P-Akt, P-ERK1, P-p70s6, P-janus-activated kinase
      2, and P-STAT3 in NDBRs were also blunted in DBRs. H9C2 cells raised in 25 mmol/l
      compared with 5.56 mmol/l glucose media also demonstrated reduced morphine
      induced P-GSK3beta, P-Akt, P-STAT3, and P-ERK1 after 15 min. Hence, acute GSK
      inhibition may provide a novel therapeutic strategy for diabetic patients during
      an acute myocardial infarction, whereas morphine is less effective due to
      signaling events that adversely affect GSK3beta.

PMID- 17192475
TI  - Genotype-by-sex interaction on fasting insulin concentration: the HyperGEN study.
AB  - Recent studies have demonstrated the importance of sex effects on the underlying
      genetic architecture of insulin-related traits. To explore sex-specific genetic
      effects on fasting insulin, we tested for genotype-by-sex interaction and
      conducted linkage analysis of fasting insulin in Hypertension Genetic
      Epidemiology Network families. Hypertensive siblings and their first-degree
      relatives were recruited from five field centers. We performed a genome scan for
      quantitative trait loci influencing fasting insulin among 1,505 European
      Americans and 1,616 African Americans without diabetes. Sex-stratified linear
      regression models, adjusted for race, center, and age, were explored. The
      Mammalian Genotyping Service typed 391 microsatellite markers, spaced roughly 9
      cM. Variance component linkage analysis was performed in SOLAR using ethnic
      specific marker allele frequencies and multipoint IBDs calculated in MERLIN. We
      detected a quantitative trait locus influencing fasting insulin in female
      subjects (logarithm of odds [LOD] = 3.4) on chromosome 2 at 95 cM (between
      GATA69E12 and GATA71G04) but not in male subjects (LOD = 0.0, P for interaction =
      0.007). This sex-specific signal at 2p13.2 was detected in both European-American
      (LOD = 2.1) and African-American (LOD = 1.2) female subjects. Our findings
      overlap with several other linkage reports of insulin-related traits and
      demonstrate the importance of considering complex context-dependent interactions
      in the search for insulin-related genes.

PMID- 17192476
TI  - Exendin-4 potently decreases ghrelin levels in fasting rats.
AB  - Ghrelin is a potent orexigenic and adipogenic hormone that strongly influences
      fat deposition and the generation of hunger in obesity. Indeed, hyperghrelinemia
      appears to promote an increase in food intake as seen in Prader-Willi Syndrome
      (PWS). Exendin (Ex)-4 is an agonist of the glucagon-like peptide (GLP)-1 receptor
      (GLP-1r) that has anorexigenic and fat-reducing properties. Here, we report that
      Ex-4 reduces the levels of ghrelin by up to 74% in fasted rats. These effects are
      dose dependent and long lasting (up to 8 h), and they can be detected after both
      central and peripheral administration of Ex-4. Suppression of ghrelin was neither
      mimicked by GLP-1(7-36)-NH(2) nor blocked by the GLP-1r antagonist Ex-(9-39).
      Moreover, it was independent of the levels of leptin and insulin. The decrease in
      ghrelin levels induced by Ex-4 may explain the reduced food intake in fasted
      rats, justifying the more potent anorexigenic effects of Ex-4 when compared with
      GLP-1. As well as the potential benefits of Ex-4 in type 2 diabetes, the potent
      effects of Ex-4 on ghrelin make it tempting to speculate that Ex-4 could offer a
      therapeutic option for PWS and other syndromes characterized by substantial
      amounts of circulating ghrelin.

PMID- 17192477
TI  - Role for mitochondrial reactive oxygen species in brain lipid sensing: redox
      regulation of food intake.
AB  - The ability for the brain to sense peripheral fuel availability is mainly
      accomplished within the hypothalamus, which detects ongoing systemic nutrients
      and adjusts food intake and peripheral metabolism as needed. Here, we
      hypothesized that mitochondrial reactive oxygen species (ROS) could trigger
      sensing of nutrients within the hypothalamus. For this purpose, we induced acute
      hypertriglyceridemia in rats and examined the function of mitochondria in the
      hypothalamus. Hypertriglyceridemia led to a rapid increase in the mitochondrial
      respiration in the ventral hypothalamus together with a transient production of
      ROS. Cerebral inhibition of fatty acids-CoA mitochondrial uptake prevented the
      hypertriglyceridemia-stimulated ROS production, indicating that ROS derived from
      mitochondrial metabolism. The hypertriglyceridemia-stimulated ROS production was
      associated with change in the intracellular redox state without any noxious
      cytotoxic effects, suggesting that ROS function acutely as signaling molecules.
      Moreover, cerebral inhibition of hypertriglyceridemia-stimulated ROS production
      fully abolished the satiety related to the hypertriglyceridemia, suggesting that
      hypothalamic ROS production was required to restrain food intake during
      hypertriglyceridemia. Finally, we found that fasting disrupted the
      hypertriglyceridemia-stimulated ROS production, indicating that the redox
      mechanism of brain nutrient sensing could be modulated under physiological
      conditions. Altogether, these findings support the role of mitochondrial ROS as
      molecular actors implied in brain nutrient sensing.

PMID- 17192478
TI  - Mice with a deletion in the gene for CCAAT/enhancer-binding protein beta are
      protected against diet-induced obesity.
AB  - The CCAAT/enhancer-binding protein beta (C/EBPbeta) is required for adipocyte
      differentiation and maturation. We have studied the role of the transcription
      factor, C/EBPbeta, in the development of diet-induced obesity. Mice with a
      deletion in the gene for C/EBPbeta (C/EBPbeta(-/-)) and wild-type mice were fed a
      high-fat diet (60% fat) for 12 weeks. The C/EBPbeta(-/-) mice lost body fat,
      whereas the wild-type mice increased their total body fat on a high-fat diet. The
      C/EBPbeta(-/-) mice had lower levels of blood triglycerides, free fatty acids,
      cholesterol, and hepatic triglyceride accumulation compared with the wild-type
      mice, thus protecting them from diet-induced obesity and fatty liver on a high
      fat diet. Deletion of C/EBPbeta gene resulted in greatly reducing hepatic
      lipogenic genes, acetyl CoA carboxylase, and fatty acid synthase and increasing
      the expression of beta-oxidation genes in the brown adipose tissue. CO(2)
      production was significantly higher in the C/EBPbeta(-/-) mice as was the level
      of uncoupling protein (UCP)-1 and UCP-3 in the muscle. In conclusion, the
      transcription factor C/EBPbeta is an important regulator in controlling lipid
      metabolism and in the development of diet-induced obesity.

PMID- 17192479
TI  - Preferential uptake of dietary Fatty acids in adipose tissue and muscle in the
      postprandial period.
AB  - Despite consistent evidence that abnormalities of fatty acid delivery and storage
      underlie the metabolic defects of insulin resistance, physiological pathways by
      which fat is stored in adipose tissue and skeletal muscle are not clear. We used
      a combination of stable isotope labeling and arteriovenous difference
      measurements to elucidate pathways of postprandial fat deposition in adipose
      tissue and skeletal muscle in healthy humans. A test meal containing [U
      (13)C]palmitate was combined with intravenous infusion of [(2)H(2)]palmitate to
      label plasma fatty acids and VLDL-triglyceride. Both dietary (chylomicron) and
      VLDL-triglyceride were cleared across adipose tissue and muscle, though with
      greater fractional extraction of the chylomicron-triglyceride. In adipose tissue
      there was significant uptake of plasma nonesterified fatty acids (NEFAs) in the
      postprandial but not the fasting state. However, this was minor in comparison
      with chylomicron-triglyceride fatty acids. We modeled the fate of fatty acids
      released by lipoprotein lipase (LPL). There was clear preferential uptake of
      these fatty acids compared with plasma NEFAs. In muscle, there was unexpected
      evidence for release of LPL-derived fatty acids into the plasma. With this
      integrative physiological approach, we have revealed hidden complexities in
      pathways of fatty acid uptake in adipose tissue and skeletal muscle.

PMID- 17192480
TI  - Altered natural killer cells in type 1 diabetic patients.
AB  - Evidence from animal models suggests that natural killer (NK) cells can be
      important players in the development of type 1 diabetes, although data in humans
      are still sparse. We studied the frequency and activation state of blood NK cells
      at different stages of human type 1 diabetes, and whether genetic or phenotypic
      NK cell peculiarities could be associated with an early onset of diabetes. The
      onset period is marked by a slight reduction in blood NK cells, but these are
      unusually activated in some patients (gamma-interferon expression). This
      activation status does not correlate, however, with a particularly young age at
      onset. In contrast, NK cells in patients with long-standing type 1 diabetes had a
      markedly lower expression of p30/p46 NK-activating receptor molecules compared
      with those of control subjects. A slightly decreased expression of NKG2D in all
      type 1 diabetic patients relative to control subjects was observed, independent
      of the duration of disease, parallel to prior observations in the NOD mouse.
      Finally, type 1 diabetic patients had an increased frequency of KIR gene
      haplotypes that include the activating KIR2DS3 gene, with a genetic interaction
      between the KIR and HLA complexes. The reduced activation of NK cells in
      individuals with long-standing type 1 diabetes would seem to be a consequence
      rather than a cause, but other peculiarities may relate to type 1 diabetes
      pathogenesis.

PMID- 17192481
TI  - Modulating protective and pathogenic CD4+ subsets via CD137 in type 1 diabetes.
AB  - CD137 (TNFRSF9) is an activation-inducible T-cell costimulatory molecule and a
      member of the tumor necrosis factor (TNF) receptor superfamily. Cd137 is also a
      candidate gene (in the Idd9.3 interval) for autoimmune diabetes in NOD mice.
      Here, we demonstrate that anti-CD137 treatment protects NOD mice from diabetes.
      Anti-CD137-treated mice are not protected from insulitis and still harbor
      pathogenic T-cells, as demonstrated by transfer studies. Transfer of CD4(+), but
      not CD8(+), cells from anti-CD137-treated pre-diabetic NOD mice into NOD-scid
      mice delayed diabetes onset. Anti-CD137 treatment significantly increased the
      number of CD4(+)CD25(+) cells, which demonstrated intracellular Foxp3 expression
      and in vitro suppressive activity. The CD4(+)CD25(+) cell subset from anti-CD137
      treated mice transferred complete protection from diabetes, whereas the
      CD4(+)CD25(-) cell subset offered no significant protection. Anti-CD137 treatment
      of NOD-scid recipients of diabetic spleen cells, however, hastened the onset of
      disease, showing that the effect of anti-CD137 treatment depends on the balance
      of pathogenic and protective cells. These results support a critical role for
      CD137 acting in the early phase of autoimmune diabetes to enhance regulatory cell
      production. Disease-associated CD137 alleles are likely ineffectual at
      stimulating a regulatory T-cell population sufficient to prevent disease.

PMID- 17192482
TI  - The role of arachidonic acid and its metabolites in insulin secretion from human
      islets of langerhans.
AB  - The roles played by arachidonic acid and its cyclooxygenase (COX)-generated and
      lipoxygenase (LOX)-generated metabolites have been studied using rodent islets
      and insulin-secreting cell lines, but very little is known about COX and LOX
      isoform expression and the effects of modulation of arachidonic acid generation
      and metabolism in human islets. We have used RT-PCR to identify mRNAs for
      cytosolic phospholipase A(2) (cPLA(2)), COX-1, COX-2, 5-LOX, and 12-LOX in
      isolated human islets. COX-3 and 15-LOX were not expressed by human islets.
      Perifusion experiments with human islets indicated that PLA(2) inhibition
      inhibited glucose-stimulated insulin secretion, whereas inhibitors of COX-2 and
      12-LOX enzymes enhanced basal insulin secretion and also secretory responses
      induced by 20 mmol/l glucose or by 50 mumol/l arachidonic acid. Inhibition of COX
      1 with 100 mumol/l acetaminophen did not significantly affect glucose-stimulated
      insulin secretion. These data indicate that the stimulation of insulin secretion
      from human islets in response to arachidonic acid does not require its metabolism
      through COX-2 and 5-/12-LOX pathways. The products of COX-2 and LOX activities
      have been implicated in cytokine-mediated damage of beta-cells, so selective
      inhibitors of these enzymes would be expected to have a dual protective role in
      diabetes: they would minimize beta-cell dysfunction while maintaining insulin
      secretion through enhancing endogenous arachidonic acid levels.

PMID- 17192483
TI  - Dominant-negative alpha-subunit of farnesyl- and geranyltransferase inhibits
      glucose-stimulated, but not KCl-stimulated, insulin secretion in INS 832/13
      cells.
AB  - The majority of small G-proteins undergo posttranslational modifications (e.g.,
      isoprenylation) at their C-terminal cysteine residues. Such modifications
      increase their hydrophobicity, culminating in translocation of the modified
      proteins to their relevant membranous sites for interaction with their respective
      effectors. Previously, we reported glucose-dependent activation and membrane
      association of Rac1 in INS 832/13 cells. We also demonstrated modulatory roles
      for Rac1/GDP dissociation inhibitor in glucose-stimulated insulin secretion
      (GSIS) in INS 832/13 cells, further affirming roles for Rac1 in GSIS. Herein, we
      demonstrate that geranylgeranyltransferase inhibitor-2147 (GGTI-2147), an
      inhibitor of protein prenylation, markedly increased cytosolic accumulation of
      Rac1 and elicited significant inhibition of GSIS from INS 832/13 cells. In the
      current study, we also examined the localization of protein prenyltransferases
      (PPTases) and regulation of GSIS by PPTases in INS 832/13 cells. Western blot
      analyses indicated that the regulatory alpha-subunit and the structural beta
      subunit of PPTase holoenzyme are predominantly cytosolic in their distribution.
      Overexpression of an inactive mutant of the regulatory alpha-subunit of PPTase
      markedly attenuated glucose- but not KCl-induced insulin secretion from INS
      832/13 cells. Together, our findings provide the first evidence for the
      regulation of GSIS by PPTase in INS 832/13 cells. Furthermore, they support our
      original hypothesis that prenylation of specific G-proteins may be necessary for
      GSIS.

PMID- 17192484
TI  - The effect of borderline diabetes on the risk of dementia and Alzheimer's
      disease.
AB  - To verify the hypothesis that borderline diabetes may increase the risk of
      dementia and Alzheimer's disease, a community-based cohort of 1,173 dementia- and
      diabetes-free individuals aged >or=75 years was longitudinally examined three
      times to detect patients with dementia and Alzheimer's disease (Diagnostic and
      Statistical Manual of Mental Disorders, Revised Third Edition criteria).
      Borderline diabetes was defined as a random plasma glucose level of 7.8-11.0
      mmol/l. Data were analyzed using Cox proportional hazards models. During the 9
      year follow-up, 397 subjects developed dementia, including 307 Alzheimer's cases.
      At baseline, 47 subjects were identified with borderline diabetes. Borderline
      diabetes was associated with adjusted hazard ratios (95% CIs) of 1.67 (1.04-2.67)
      for dementia and 1.77 (1.06-2.97) for Alzheimer's disease; the significant
      associations were present after additional adjustment for future development of
      diabetes. Stratified analysis suggested a significant association between
      borderline diabetes and Alzheimer's disease only among noncarriers of APOE
      epsilon4 allele. There was an interaction between borderline diabetes and severe
      systolic hypertension on the risk of Alzheimer's disease (P = 0.04). We conclude
      that borderline diabetes is associated with increased risks of dementia and
      Alzheimer's disease; the risk effect is independent of the future development of
      diabetes. Borderline diabetes may interact with severe systolic hypertension to
      multiply the risk of Alzheimer's disease.

PMID- 17192485
TI  - Antecedent hindbrain glucoprivation does not impair the counterregulatory
      response to hypoglycemia.
AB  - Recurrent hypoglycemia impairs hormonal counterregulatory responses (CRRs) to
      further bouts of hypoglycemia. The hypothalamus and hindbrain are both critical
      for sensing hypoglycemia and triggering CRRs. Hypothalamic glucose sensing sites
      are implicated in the pathogenesis of defective CRRs; however, the contribution
      of hindbrain glucose sensing has not been elucidated. Using a rat model, we
      compared the effect of antecedent glucoprivation targeting hindbrain or
      hypothalamic glucose sensing sites with the effect of antecedent recurrent
      hypoglycemia on CRR to hypoglycemia induced 24 h later. Recurrent hypoglycemia
      decreased sympathoadrenal (1,470 +/- 325 vs. 3,811 +/- 540 pg/ml in controls [t =
      60 min], P = 0.001) and glucagon secretion (222 +/- 43 vs. 494 +/- 56 pg/ml in
      controls [t = 60]), P = 0.003) in response to hypoglycemia. Antecedent 5-thio
      glucose (5TG) injected into the hindbrain did not impair sympathoadrenal (3,806
      +/- 344 pg/ml [t = 60]) or glucagon (513 +/- 56 pg/ml [t = 60]) responses to
      subsequent hypoglycemia. However, antecedent 5TG delivered into the third
      ventricle was sufficient to blunt CRRs to hypoglycemia. These results show that
      hindbrain glucose sensing is not involved in the development of defective CRRs.
      However, neural substrates surrounding the third ventricle are particularly
      sensitive to glucoprivic stimulation and may contribute importantly to the
      development of defective CRRs.

PMID- 17192486
TI  - Inhibition of caspase-1/interleukin-1beta signaling prevents degeneration of
      retinal capillaries in diabetes and galactosemia.
AB  - The proinflammatory cytokine, interleukin (IL)-1beta, is known to induce vascular
      dysfunction and cell death. We investigated the role of IL-1beta and caspase-1
      (the enzyme that produces it) in diabetes-induced degeneration of retinal
      capillaries. Caspase-1 activity is increased in retinas of diabetic and
      galactosemic mice and diabetic patients. First, we investigated the effect of
      agents known to inhibit caspase-1 (minocycline and tetracycline) on IL-1beta
      production and retinal capillary degeneration in diabetic and galactose-fed mice.
      Second, we examined the effect of genetic deletion of the IL-1beta receptor on
      diabetes-induced caspase activities and retinal capillary degeneration. Diabetic
      and galactose-fed mice were injected intraperitoneally with minocycline or
      tetracycline (5 mg/kg). At 2 months of diabetes, minocycline inhibited
      hyperglycemia-induced caspase-1 activity and IL-1beta production in the retina.
      Long-term administration of minocycline prevented retinal capillary degeneration
      in diabetic (6 months) and galactose-fed (13 months) mice. Tetracycline inhibited
      hyperglycemia-induced caspase-1 activity in vitro but not in vivo. Mice deficient
      in the IL-1beta receptor were protected from diabetes-induced caspase activation
      and retinal pathology at 7 months of diabetes. These results indicate that the
      caspase-1/IL-1beta signaling pathway plays an important role in diabetes-induced
      retinal pathology, and its inhibition might represent a new strategy to inhibit
      capillary degeneration in diabetic retinopathy.

PMID- 17192487
TI  - Transforming growth factor-beta2 and connective tissue growth factor in
      proliferative vitreoretinal diseases: possible involvement of hyalocytes and
      therapeutic potential of Rho kinase inhibitor.
AB  - The critical association of connective tissue growth factor (CTGF), which is
      thought to be one of the downstream mediators of transforming growth factor-beta
      (TGF-beta), with vitreoretinal diseases remains to be clarified. In the current
      study, we first demonstrated the correlation between the concentrations of TGF
      beta2 as well as CTGF in the vitreous and CTGF gene regulation in cultured
      hyalocytes. Concentrations of TGF-beta2 and CTGF in the vitreous from patients
      with proliferative vitreoretinal diseases were significantly higher than in those
      with nonproliferative diseases, and there was a positive correlation between
      their concentrations (r = 0.320, P < 0.01). Cultured hyalocytes expressed CTGF
      mRNA, which was enhanced in the presence of TGF-beta2, associated with nuclear
      accumulation of Smad4. TGF-beta2-dependent Smad4 translocation and CTGF gene
      expression were mediated through Rho kinase and at least partially via p38
      mitogen-activated protein kinase. Finally, fasudil, a Rho kinase inhibitor
      already in clinical use, inhibited both Smad4 translocation and CTGF gene
      expression. In conclusion, combined effects of TGF-beta2 and CTGF appear to be
      involved in the pathogenesis of proliferative vitreoretinal diseases. Hyalocytes
      may be a possible source of CTGF and thus might play a role in vitreoretinal
      interface diseases. Furthermore, Rho kinase inhibitors might have therapeutic
      potential to control fibrotic disorders in the eye.

PMID- 17192488
TI  - Prevention and treatment of obesity, insulin resistance, and diabetes by bile
      acid-binding resin.
AB  - Bile acid-binding resins, such as cholestyramine and colestimide, have been
      clinically used as cholesterol-lowering agents. These agents bind bile acids in
      the intestine and reduce enterohepatic circulation of bile acids, leading to
      accelerated conversion of cholesterol to bile acids. A significant improvement in
      glycemic control was reported in patients with type 2 diabetes whose
      hyperlipidemia was treated with bile acid-binding resins. To confirm the effect
      of such drugs on glucose metabolism and to investigate the underlying mechanisms,
      an animal model of type 2 diabetes was given a high-fat diet with and without
      colestimide. Diet-induced obesity and fatty liver were markedly ameliorated by
      colestimide without decreasing the food intake. Hyperglycemia, insulin
      resistance, and insulin response to glucose, as well as dyslipidemia, were
      markedly and significantly ameliorated by the treatment. Gene expression of the
      liver indicated reduced expression of small heterodimer partner, a pleiotropic
      regulator of diverse metabolic pathways, as well as genes for both fatty acid
      synthesis and gluconeogenesis, by treatment with colestimide. This study provides
      a molecular basis for a link between bile acids and glucose metabolism and
      suggests the bile acid metabolism pathway as a novel therapeutic target for the
      treatment of obesity, insulin resistance, and type 2 diabetes.

PMID- 17192489
TI  - Combined use of rosiglitazone and fenofibrate in patients with type 2 diabetes:
      prevention of fluid retention.
AB  - Elevated plasma free fatty acid (FFA) levels are responsible for much of the
      insulin resistance in obese patients with type 2 diabetes. To lower plasma FFA
      levels effectively and long term, we have treated eight obese patients with type
      2 diabetes for 2 months with placebo followed by 2 months of treatment with a
      combination of rosiglitazone (RGZ) (8 mg/day) and fenofibrate (FFB) (160 mg/day)
      in a single-blind placebo-controlled study design. Compared with placebo, RGZ/FFB
      lowered mean 24-h plasma FFA levels 30% (P < 0.03) and mean 24-h glucose levels
      23% (P < 0.03) and increased insulin-stimulated glucose uptake (glucose rate of
      disappearance [G(R)(d)], determined using euglycemic-hyperinsulinemic clamp) 442%
      (P < 0.01), oral glucose tolerance (area under the curve for 3-h oral glucose
      tolerance test) 28% (P < 0.05), and plasma adiponectin levels 218% (P < 0.01).
      These RGZ/FFB results were compared with results obtained in five patients
      treated with RGZ alone. RGZ/FFB prevented the fluid retention usually associated
      with RGZ (-1.6 vs. 5.6%, P < 0.05), lowered fasting plasma FFA more effectively
      than RGZ alone (-22 vs. 5%, P < 0.05), and tended to be more effective than RGZ
      alone in lowering A1C (-0.9 vs. -0.4%) and triglyceride levels (-38 vs. -5%) and
      increasing G(Rd) (442 vs. 330%). We conclude that RGZ/FFB is a promising new
      therapy for type 2 diabetes that lowers plasma FFA more than RGZ alone and in
      contrast to RGZ does not cause water retention and weight gain.

PMID- 17192491
TI  - A functional polymorphism in the manganese superoxide dismutase gene and diabetic
      nephropathy.
AB  - Oxidative stress has been suggested to contribute to the development of diabetic
      nephropathy. Manganese superoxide dismutase (MnSOD) protects the cells from
      oxidative damage by scavenging free radicals. The demand for antioxidants is
      increased by smoking, which could disturb the balance between antioxidants and
      radicals. The present study aimed to determine whether a valine/alanine
      polymorphism in MnSOD (V16A, rs4880), alone or in combination with smoking, can
      contribute to development of diabetic nephropathy in 1,510 Finnish and Swedish
      patients with type 1 diabetes. Overt diabetic nephropathy (n = 619) was defined
      as having an albumin excretion rate (AER) >200 microg/min or renal replacement
      therapy; incipient diabetic nephropathy was defined as having an AER of 20-200
      microg/min (n = 336). The control subjects had diabetes duration of >or=20 years,
      without albuminuria (AER <20 microg/min) and without antihypertensive treatment
      (n = 555). In addition to male sex and elevated A1C, smoking was significantly
      associated with diabetic nephropathy (overt plus incipient), odds ratio (OR) 2.00
      (95% CI 1.60-2.50). When controlling for age at onset, diabetes duration, A1C,
      smoking, and sex, the Val/Val genotype was associated with an increase in risk of
      diabetic nephropathy (1.32 [1.00-1.74], P = 0.049). When evaluating the combined
      effect of genotype and smoking, we used logistic regression with stratification
      according to smoking status and genotype. The high-risk group (ever smoking plus
      Val/Val genotype) had 2.52 times increased risk of diabetic nephropathy (95% CI
      1.73-3.69) compared with the low-risk group, but no departure from additivity was
      found. Our results indicate that smoking and homozygosity for the MnSOD Val
      allele is associated with an increased risk of diabetic nephropathy, which
      supports the hypothesis that oxidative stress contributes to the development of
      diabetic nephropathy.

PMID- 17192490
TI  - Screening of 134 single nucleotide polymorphisms (SNPs) previously associated
      with type 2 diabetes replicates association with 12 SNPs in nine genes.
AB  - More than 120 published reports have described associations between single
      nucleotide polymorphisms (SNPs) and type 2 diabetes. However, multiple studies of
      the same variant have often been discordant. From a literature search, we
      identified previously reported type 2 diabetes-associated SNPs. We initially
      genotyped 134 SNPs on 786 index case subjects from type 2 diabetes families and
      617 control subjects with normal glucose tolerance from Finland and excluded from
      analysis 20 SNPs in strong linkage disequilibrium (r(2) > 0.8) with another typed
      SNP. Of the 114 SNPs examined, we followed up the 20 most significant SNPs (P <
      0.10) on an additional 384 case subjects and 366 control subjects from a
      population-based study in Finland. In the combined data, we replicated
      association (P < 0.05) for 12 SNPs: PPARG Pro12Ala and His447, KCNJ11 Glu23Lys
      and rs5210, TNF -857, SLC2A2 Ile110Thr, HNF1A/TCF1 rs2701175 and GE117881_360,
      PCK1 -232, NEUROD1 Thr45Ala, IL6 -598, and ENPP1 Lys121Gln. The replication of 12
      SNPs of 114 tested was significantly greater than expected by chance under the
      null hypothesis of no association (P = 0.012). We observed that SNPs from genes
      that had three or more previous reports of association were significantly more
      likely to be replicated in our sample (P = 0.03), although we also replicated 4
      of 58 SNPs from genes that had only one previous report of association.

PMID- 17192492
TI  - Genetic control of alternative splicing in the TAP2 gene: possible implication in
      the genetics of type 1 diabetes.
AB  - The transporter 2, ATP-binding cassette, subfamily B (TAP2) is involved in the
      transport of antigenic peptides to HLA molecules. Coding TAP2 polymorphisms shows
      a strong association with type 1 diabetes, but it is not clear whether this
      association may be entirely due to linkage disequilibrium with HLA DR and DQ.
      Functionally, rat Tap2 nonsynonymous single-nucleotide polymorphisms (nsSNPs)
      confer differential selectivity for antigenic peptides, but this was not shown to
      be the case for human TAP2 nsSNPs. In the human, differential peptide selectivity
      is rather conferred by two splicing isoforms with alternative carboxy terminals.
      Here, we tested the hypothesis that alleles at the coding SNPs favor different
      splicing isoforms, thus determining peptide selectivity indirectly. This may be
      the basis for independent contribution to the type 1 diabetes association. In RNA
      from heterozygous lymphoblastoid lines, we measured the relative abundance of
      each SNP haplotype in each isoform. In isoform NM_000544, the G (Ala) allele at
      665 Thr>Ala (rs241447) is more than twice as abundant as A (Thr) (GA = 2.2 +/-
      0.4, P = 1.5 x 10(-4)), while isoform NM_018833 is derived almost exclusively
      from chromosomes carrying A (AG = 18.1 +/- 5.6, P = 2.04 x 10(-7)). In 889
      Canadian children with type 1 diabetes, differential transmission of parental
      TAP2 alleles persisted (P = 0.011) when analysis was confined to chromosomes
      carrying only DQ*02 alleles, which mark a conserved DR-DQ haplotype, thus
      eliminating most of the variation at DR-DQ. Thus, we present evidence of TAP2
      association with type 1 diabetes that is independent of HLA DR-DQ and describe a
      plausible functional mechanism based on allele dependence of splicing into
      isoforms known to have differential peptide selectivities.

PMID- 17192493
TI  - Common genetic variations in CCK, leptin, and leptin receptor genes are
      associated with specific human eating patterns.
AB  - Obesity has a heritable component; however, the heterogeneity of obesity
      complicates dissection of its genetic background. In this study, we therefore
      focused on eating patterns as specific traits within obesity. These traits have a
      heritable component; genes associated with a specific eating pattern have not yet
      been reported at the population level. In this study, we determined whether
      genetic variations in cholecystokinin (CCK) and leptin genes underlie specific
      eating patterns. We selected obese individuals showing extreme snacking behavior
      or use of excessive portion sizes from a large population-based sample (n =
      17,357) from the Prospect-EPIC (European Prospective Study into Cancer and
      Nutrition) study. Using allele-specific PCRs, we tested several single nucleotide
      polymorphisms in the candidate genes and performed haplotype analysis. Obese
      carriers of common allelic variations in leptin or the leptin receptor gene had
      an increased risk to display extreme snacking behavior. In contrast, obese
      carriers of common allelic variations in CCK had an increased risk to eating
      increased meal sizes. In conclusion, we identified common allelic variants
      specifically associated with distinctly different eating patterns, namely extreme
      snacking behavior or excessive portion size.

PMID- 17192494
TI  - Beta-cell regeneration: epithelial mesenchymal transition pre-EMTpted by lineage
      tracing?

PMID- 17192495
TI  - The highly conserved DRY motif of class A G protein-coupled receptors: beyond the
      ground state.
AB  - Despite extensive study of heptahelical G protein-coupled receptors (GPCRs), the
      precise mechanism of G protein activation is unknown. The role of one highly
      conserved stretch of residues, the amino acids glutamic acid/aspartic acid
      arginine-tyrosine (i.e., the E/DRY motif), has received considerable attention
      with respect to regulating GPCR conformational states. In the consensus view,
      glutamic acid/aspartic acid maintains the receptor in its ground state, because
      mutations frequently induce constitutive activity (CA). This hypothesis has been
      confirmed by the rhodopsin ground-state crystal structure and by computational
      modeling approaches. However, some class A GPCRs are resistant to CA, suggesting
      alternative roles for the glutamic acid/aspartic acid residue and the E/DRY
      motif. Here, we propose two different subgroups of receptors within class A GPCRs
      that make different use of the E/DRY motif, independent of the G protein type
      (G(s), G(i), or G(q)) to which the receptor couples. In phenotype 1 receptors,
      nonconservative mutations of the glutamic acid/aspartic acid-arginine residues,
      besides inducing CA, increase affinity for agonist binding, retain G protein
      coupling, and retain an agonist-induced response. In contrast, in second
      phenotype receptors, the E/DRY motif is more directly involved in governing
      receptor conformation and G protein coupling/recognition. Hence, mutations of the
      glutamic acid/aspartic acid residues do not induce CA. Conversely,
      nonconservative mutations of the arginine of the E/DRY motif always impair
      agonist-induced receptor responses and, generally, reduce agonist binding
      affinity. Thus, it is essential to look beyond the rhodopsin ground-state model
      of conformational activation to clarify the role of this highly conserved triplet
      in GPCR activation and function.

PMID- 17192496
TI  - Highly variable mycophenolate mofetil bioavailability following nonmyeloablative
      hematopoietic cell transplantation.
AB  - This study determined the oral bioavailability of mycophenolic acid, the active
      metabolite of mycophenolate mofetil, in patients undergoing nonmyeloablative
      hematopoietic cell transplantation. Eighteen adults receiving a preparative
      regimen containing fludarabine, cyclophosphamide, and total body irradiation were
      studied. Immune suppression consisted of cyclosporine and mycophenolate 1 g twice
      daily. Pharmacokinetic variability was high after intravenous and oral dosing.
      Intravenous dosing resulted in a median area under the curve (AUC) of 28.3 microg
      x h/mL (range, 9.96-70.4) and an oral AUC of 16.7 microg x h/mL (range, 9.38
      35.3). Cmax after intravenous and oral dosing was 12.18 and 5.29 microg/mL,
      respectively. The median oral bioavailability was 72.3% (20.5%-172%), with 8-fold
      variability. Five patients (28%) had an oral bioavailability < or = 50%. At time
      of oral pharmacokinetics, 15 patients (83%) had an AUC(0-12) < 30 microg x h/mL.
      The initial oral dose should be at least 25% greater than the intravenous dose
      with follow-up assessment of plasma concentrations.

PMID- 17192497
TI  - Pharmacokinetics and safety of ketorolac following single intranasal and
      intramuscular administration in healthy volunteers.
AB  - Ketorolac was administered to 15 healthy volunteers in a phase 1, single-dose,
      crossover, randomized study. Subjects received open-label randomized 15- and 30
      mg intramuscular (i.m.) ketorolac and blinded randomized 15- and 30-mg intranasal
      (i.n.) ketorolac. The i.n. ketorolac was well tolerated; the only nasal symptoms
      were some instances of mild irritation. The i.n. ketorolac was rapidly and well
      absorbed (median tmax, 0.50-0.75 hours), and the half-life was approximately 5 to
      6 hours, values that were similar to those following i.m. administration.
      Relative bioavailability of i.n. compared to i.m. administration at the same
      doses was approximately 67% to 75%. Dose proportionality was noted between the 15
      and 30-mg i.n. and i.m. dose levels. Thus, i.n. ketorolac offers a therapeutic
      alternative to i.m. administration and may provide benefits in the clinical
      setting.

PMID- 17192498
TI  - Systemic availability of the active metabolite hydroxy-fasudil after
      administration of fasudil to different sites of the human gastrointestinal tract.
AB  - This study evaluated the gastrointestinal absorption of fasudil, a novel Rho
      kinase inhibitor for the treatment of stable angina, at different sites using
      remote-controlled capsules and assessed the feasibility of developing an extended
      release formulation. Ten healthy male volunteers were enrolled, and 8 subjects
      completed this single-dose, open-label, randomized, 5-way crossover study. Forty
      milligrams of fasudil HCl was administered as solution to the distal ileum and
      ascending colon, as powder to the ascending colon, and orally as an immediate
      release tablet and solution. All treatments were well-tolerated and no serious
      adverse events were observed. The mean systemic availabilities of M3 relative to
      the oral solution were 1.04 (distal ileum, solution), 1.14 (ascending colon,
      solution), 1.27 (ascending colon, powder) and 1.04 (oral tablet), indicating
      similar systemic availability of M3 after administration of fasudil HCl to
      different gastrointestinal sites. The results suggest that development of a once
      a-day extended-release formulation for fasudil HCl should be readily achievable.

PMID- 17192499
TI  - Dose-proportional intraindividual single- and repeated-dose pharmacokinetics of
      roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor.
AB  - The dose-proportional, intraindividual, single- and repeated-dose
      pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4
      inhibitor under investigation for chronic obstructive pulmonary disease and
      asthma, was investigated in healthy subjects. In an open, randomized, 2-period, 2
      sequence crossover study, 15 subjects received immediate-release tablets of
      roflumilast 250 or 500 microg as single (day 1) and as repeated, once-daily doses
      for 8 days (days 5-12). Dose-adjusted point estimates and 90% confidence
      intervals of test (500 microg)/reference (250 microg) ratios for AUC and Cmax of
      roflumilast and its pharmacologically active N-oxide metabolite after single and
      repeated dosing were all within the standard equivalence acceptance range (0.80,
      1.25) indicating dose proportionality. The pharmacokinetic properties of both
      roflumilast dosage forms provide clinically relevant evidence of predictable,
      intraindividual total (AUC) and maximum (Cmax) exposure of roflumilast and
      roflumilast N-oxide. Repeated oral dosing with roflumilast 250 and 500 microg
      once daily was well tolerated.

PMID- 17192500
TI  - Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination
      tablets of pioglitazone and metformin. Effect of body weight, gender, and race on
      systemic exposures of each drug.
AB  - Bioavailability of pioglitazone and metformin, in 2 dose strengths, given either
      as a fixed-dose combination tablet or as coadministration of commercial tablets
      (coad), was studied in young healthy subjects in 2 separate studies. In study I
      (n = 63), single oral doses of 15-mg pioglitazone/500-mg metformin fixed-dose
      combination tablets or equivalent doses of commercial tablets were administered,
      in a fasting state, in an open-label, randomized, crossover study with a 7-day
      washout period between treatments. Study II (n = 61) was similar in design to
      study I, except the 15/850-mg fixed-dose combination tablet and coad treatments
      were evaluated. Least squares mean (fixed-dose combination/coad) ratios and 90%
      confidence intervals of the ratios for the 15/500-mg dose strength for the
      maximum observed serum concentration (Cmax) and area under the serum
      concentration-time curve from time 0 to infinity (AUC(infinity)) were 0.95 (0.86
      1.05) and 1.02 (0.98-1.08), respectively, for pioglitazone and 0.99 (0.95-1.03)
      and 1.03 (0.98-1.08), respectively, for metformin. Bioequivalency for
      pioglitazone and metformin between fixed-dose combination tablets and coad
      treatments was met for both strengths of fixed-dose combination tablets. In a
      post hoc meta-analysis of combined data from the 2 studies (n = 124), there was
      considerable overlapping in AUC(infinity) values between gender and race
      (Caucasians, Blacks, and Hispanics), making neither gender- nor racial-based
      dosing of pioglitazone or metformin necessary.

PMID- 17192501
TI  - Oral antidiabetic drugs: effect of food on absorption of pioglitazone and
      metformin from a fixed-dose combination tablet.
AB  - An open-label, randomized, crossover study involving 28 healthy subjects was
      conducted to compare the peak (Cmax) and total (AUC(lqc), AUC(infinity))
      exposures to pioglitazone and metformin after single-dose administration of a
      fixed-dose combination tablet containing 15 mg of pioglitazone plus 850 mg
      metformin when given under fasted versus fed states, with a washout period of 7
      days between treatments. Two different fixed-dose combination formulations
      (bilayer and pioglitazone-micronized fixed-dose combination tablets) were tested.
      The pioglitazone-micronized fixed-dose combination formulation was selected for
      clinical development and regulatory approval; the present study describes food
      effect results with this formulation. For pioglitazone, least squares mean ratios
      (fed/fasted) and the 90% confidence intervals of these ratios were 1.05 (0.93
      1.18) for Cmax, 1.13 (1.02-1.25) for AUC(lqc), and 1.11 (1.01-1.22) for
      AUC(infinity). For metformin, these values were 0.72 (0.65-0.79) for Cmax, 0.87
      (0.81-0.94) for AUC(lqc), and 0.87 (0.81-0.94) for AUC(infinity). Dosing with
      food resulted in median prolongation of tmax values by 1.5 hours for metformin
      and 2.0 hours for pioglitazone. Because bioequivalency criteria were met
      (fed/fasted 90% confidence interval between 0.80 and 1.25) for both pioglitazone
      and metformin AUC, fixed-dose combination tablets can be taken with or without
      food, but to minimize gastrointestinal adverse effects of metformin, the fixed
      dose combination tablets are recommended to be taken with food.

PMID- 17192502
TI  - Single-dose and steady-state pharmacokinetics of fentanyl buccal tablet in
      healthy volunteers.
AB  - This study evaluated the single-dose and steady-state pharmacokinetics of
      fentanyl buccal tablet 400 microg in healthy adult volunteers. After receiving
      naltrexone 50 mg to block opioid receptor-mediated effects of fentanyl, subjects
      received fentanyl buccal tablet 400 microg on day 1, then every 6 hours from day
      4 to day 9 (21 doses). Naltrexone 50 mg was administered every 12 hours
      throughout the study. Plasma fentanyl concentrations were determined for 72 hours
      after administration of fentanyl buccal tablet 400 microg on day 1 and the last
      dose of fentanyl buccal tablet 400 microg on day 9. Following single- and
      multiple-dose administration of fentanyl buccal tablet, the median time to
      maximum concentration (tmax) was 52.2 and 49.8 minutes, respectively. Peak plasma
      concentration of fentanyl (Cmax) was 0.88 ng/mL for the single-dose regimen and
      1.77 ng/mL for the multiple-dose regimen. Steady state was reached within 5 days,
      consistent with the observed median half-life of approximately 22 hours following
      multiple doses. Observed accumulation of fentanyl after multiple doses of
      fentanyl buccal tablet was slightly greater than would be expected based on the
      single-dose data. This was attributed to the redistribution of fentanyl from a
      deep tissue compartment into the plasma. This study indicates that fentanyl
      buccal tablet has predictable pharmacokinetics following multiple-dose
      administration.

PMID- 17192503
TI  - Dose-proportional pharmacokinetics of d-threo-methylphenidate after a repeated
      action release dosage form.
AB  - A bimodal extended-release formulation of d-methylphenidate (d-MPH) has been
      developed to enable fast onset of action and once-daily administration in
      patients with attention deficit hyperactivity disorder. The authors studied the
      dose proportionality of extended-release d-MPH pharmacokinetics. Twenty-five
      healthy adult volunteers received 5, 10, 20, 30, and 40 mg d-MPH in a crossover
      study with 7 days between doses. All doses were well tolerated. Dose
      proportionality was shown for all dose-dependent pharmacokinetic parameters.
      Geometric means (%gCV) for the first Cmax peak, Cmax0-4, were 3.25 (29.0%), 6.05
      (27.1%), 12.6 (31.9%), 18.5 (31.9%), and 25.2 ng/mL (29.3%) for d-MPH 5, 10, 20,
      30, and 40 mg, respectively. Geometric means (%gCV) for Cmax4-10 were 3.18
      (27.5%), 5.84 (27.7%), 12.5 (31.7%), 17.7 (31.6%), and 23.6 ng/mL (29.0%),
      respectively. Geometric means for AUC(0-infinity) were 24.3 (30.7%), 45.9
      (30.2%), 96.4 (35.5%), 144 (33.3%), and 195 ng x h/mL (30.9%), respectively. The
      pharmacokinetics of once-daily extended-release d-MPH are proportional to the
      dose.

PMID- 17192504
TI  - Significant pharmacokinetic and pharmacodynamic interaction of warfarin with the
      NO-independent sGC activator HMR1766.
AB  - HMR1766 is a new nitric oxide (NO)-independent activator of soluble guanylyl
      cyclase (sGC) in development for the treatment of cardiovascular diseases and
      chronic heart failure. A significant fraction of patients to be treated with
      HMR1766 is expected to be maintained on warfarin. Because HMR1766 is an inhibitor
      and warfarin a substrate of CYP2C9, the authors studied whether warfarin
      pharmacokinetics and pharmacodynamics are influenced by HMR1766. Eighteen healthy
      males were to receive a single oral dose of 20 mg warfarin each under steady
      state conditions of HMR1766 or placebo. Plasma concentrations of HMR1766, (R)-
      and (S)-warfarin, and its 7-hydroxy-metabolites were determined using high
      performance liquid chromatography and prothrombin time, and the international
      standardized ratio was determined by the nephelometric method. (S)-Warfarin
      AUC(inf) and t(1/2) were 106,471 h x microg/L and 82.92 hours versus 33,148 h x
      microg/L under HMR1766 and 31.72 hours under placebo, and the maximum decrease in
      prothrombin time values after warfarin dosing was 58.75% versus 39.94%. These
      data demonstrate a CYP2C9-mediated pharmacokinetic interaction with
      pharmacodynamic, clinically relevant consequences, which might require warfarin
      dose adjustment.

PMID- 17192505
TI  - The role of SN-38 exposure, UGT1A1*28 polymorphism, and baseline bilirubin level
      in predicting severe irinotecan toxicity.
AB  - Irinotecan, an anticancer drug, is associated with severe and potentially fatal
      diarrhea and neutropenia. The objective of this analysis was to evaluate the role
      of SN-38 exposure, the active metabolite of irinotecan, UGT1A1 genotypes, and
      baseline bilirubin on the maximum decrease (nadir) in absolute neutrophil counts
      following irinotecan. This analysis extended the work of a previous study that
      examined the effect of UGT1A1 genotypes on the incidence of severe neutropenia in
      86 advanced cancer patients following irinotecan treatment. Regression analysis
      showed that the absolute neutrophil count nadir depended on SN-38 exposure (AUC)
      and UGT1A1*28 homozygous 7/7 genotype. An increased SN-38 AUC and the 7/7
      genotype were significantly associated with a lower absolute neutrophil count
      nadir (R2 = .49). An alternate model suggested that higher baseline bilirubin and
      the 7/7 genotype were also significantly associated with a lower absolute
      neutrophil count nadir, although with a lower coefficient of determination (R2 =
      .31). Based on these findings and other reports, the irinotecan label was
      modified to indicate the role of UGT1A1*28 polymorphism in the metabolism of
      irinotecan and the associated increased risk of severe neutropenia. The label
      modifications also included recommendations for lower starting doses of
      irinotecan in patients homozygous for the UGT1A1*28 (7/7) polymorphism.

PMID- 17192506
TI  - Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin
      pharmacokinetics in healthy subjects.
AB  - Simvastatin, a cholesterol-lowering agent, is mainly metabolized by CYP3A4/5. The
      objective of this study was to investigate the effect of CYP3A5*3 genotype on the
      pharmacokinetics of simvastatin in humans. Twenty-two men with CYP3A5*1/*1 (n =
      4), CYP3A5*1/*3 (n = 8), or CYP3A5*3/*3 (n = 10) genotypes were enrolled. Each
      subject ingested a 20-mg dose of simvastatin, and plasma simvastatin
      concentrations were measured for 12 hours after dosing. The mean (+/-SD) area
      under the plasma concentration-time curve for simvastatin in the CYP3A5*1/*1
      carriers (4.94 +/- 2.25 ng x h/mL) was significantly lower than CYP3A5*3/*3
      carriers (16.35 +/- 6.37 ng x h/mL; P = .013, Bonferroni test). The mean (+/-SD)
      oral clearance was also significantly different between CYP3A5*1/*1 carriers
      (4.80 +/- 2.35 L/h) and CYP3A5*3/*3 carriers (1.35 +/- 0.61 L/h; P < .05, Dunn's
      test). However, other pharmacokinetic parameters including peak plasma
      concentrations and half-life did not show any difference between genotype groups.
      These findings suggest that the polymorphic CYP3A5 gene affects the disposition
      of simvastatin and provides a plausible explanation for interindividual
      variability of simvastatin disposition.

PMID- 17192507
TI  - Plasma and cerebrospinal fluid concentrations of indomethacin in children after
      intravenous administration.
AB  - The objective of this study was to evaluate the cerebrospinal fluid (CSF)
      permeation of indomethacin in healthy children. The participants (n = 31, aged 4
      144 months) received indomethacin (0.35 mg/kg) as a 10-minute intravenous
      infusion prior to surgery under spinal anaesthesia. A single CSF and plasma
      sample from each individual was collected 14 to 225 minutes after the infusion.
      Indomethacin concentrations were determined from the CSF, plasma, and protein
      free plasma. Total plasma, protein-free plasma, and CSF concentrations of
      indomethacin ranged between 90 and 2200 ng/mL (median, 780 ng/mL), 0.3 and 0.8
      ng/mL (median, 0.5 ng/mL), and 0.2 and 5.0 ng/mL (median, 1.4 ng/mL),
      respectively. The CSF to plasma concentration ratio remained less than 0.01.
      There was no correlation between the administration time and CSF concentrations.
      Eleven children developed 12 nonserious adverse effects, from which 5 were
      central nervous system (CNS) effects (agitation). In conclusion, indomethacin
      permeated into the CSF of children, which enables both desired and adverse CNS
      effects of indomethacin.

PMID- 17192508
TI  - Population pharmacokinetic-based dosing of intravenous busulfan in pediatric
      patients.
AB  - The objective of this study was to characterize the pharmacokinetics (PK) of
      intravenous busulfan in pediatric patients and provide dosing recommendations.
      Twenty-four pediatric patients were treated with intravenous busulfan, 1.0 or 0.8
      mg/kg for ages < or = 4 years or > 4 years, respectively, 4 times a day for 4
      days. Dense PK sampling was performed. Body weight, age, gender, and body surface
      area were explored for effects on PK, and Monte Carlo simulations were performed
      to assess different dosing regimens. The PK of intravenous busulfan was described
      by a 1-compartment model with clearance of 4.04 L/h/20 kg and volume of
      distribution of 12.8 L/20 kg. Simulations indicated that the mg/kg and mg/m2
      regimens were similar and achieved the desired target exposure in approximately
      60% of patients. This model suggests that patients < or = 12 kg should be dosed
      at 1.1 mg/kg and those > 12 kg dosed at 0.8 mg/kg. Therapeutic drug monitoring
      and dose adjustment will further improve therapeutic targeting.

PMID- 17192509
TI  - Comparison of inhibitory effects of irbesartan and atorvastatin treatment on the
      renin angiotensin system (RAS) in veins: a randomized double-blind crossover
      trial in healthy subjects.
AB  - Experimental studies point to an interplay between hypercholesterolemia and
      hypertension, acting through the renin angiotensin system. In a crossover study
      design with 8 healthy subjects, the authors tested the hypothesis that statin
      treatment exerts renin angiotensin system-modulating effects in veins by down
      regulation of AT1-receptors, resulting in reduced Angiotensin II (Ang II)-induced
      venoconstriction and by increasing the pleiotropic Ang II-metabolite Ang-(1-7).
      Irbesartan was used as positive control. Ang II-induced venoconstriction was 49%
      +/- 9% before and 64% +/- 10% after 30 days of atorvastatin treatment compared to
      50% +/- 8% before and 15% +/- 9% after irbesartan (P = .004). Plasma angiotensin
      levels significantly increased only after irbesartan treatment (Ang II: 35 +/- 4
      vs 329 +/- 101 pg/mL [P = .02]; Ang-(1-7): 10 +/- 3 vs 35 +/- 6 pg/mL [P = .01])
      compared to atorvastatin treatment (Ang II: 26 +/- 5 vs 31 +/- 4 pg/mL [P = ns];
      Ang-(1-7): 9 +/- 2 vs 11 +/- 3 pg/mL [P = ns]). The data indicate that
      atorvastatin does not inhibit Ang II-induced venoconstriction in vivo and point
      toward a supportive role of Ang-(1-7) in contributing to the antihypertensive and
      beneficial vascular effects of irbesartan.

PMID- 17192510
TI  - Comparison of the stability, efficacy, and adverse effect profile of the
      innovator 0.005% latanoprost ophthalmic solution and a novel cyclodextrin
      containing formulation.
AB  - Recently, a new latanoprost ophthalmic solution containing cyclodextrins was
      developed. The purpose of the present work was to compare the stability, clinical
      efficacy, and adverse effect profile of this formulation with the innovator
      product. The innovator formulation was stable at 4 degrees C but exhibited
      degradation at higher temperatures, whereas the cyclodextrin-containing
      formulation was stable at temperatures up to 40 degrees C. Formulations were
      assayed in a randomized double-blind clinical study in patients with primary open
      angle glaucoma and/or ocular hypertension. Both latanoprost ophthalmic solutions
      produced comparable reduction of intraocular pressure. Conjunctival hyperemia was
      observed in 11.9% and 11.3% of the patients treated with the innovator and the
      cyclodextrin-containing formulations, respectively. There were no significant
      differences between the 2 ophthalmic solutions in efficacy or in the measured
      adverse effect. It is concluded that these 2 latanoprost ophthalmic solutions
      yield comparable efficacy and adverse effect outcomes. The cyclodextrin
      containing formulation, however, has an improved stability.

PMID- 17192511
TI  - Vildagliptin does not affect C-peptide clearance in patients with type 2
      diabetes.

PMID- 17192512
TI  - Primary prevention of cardiovascular diseases in people with diabetes mellitus: a
      scientific statement from the American Heart Association and the American
      Diabetes Association.
AB  - The American Heart Association (AHA) and the American Diabetes Association (ADA)
      have each published guidelines for cardiovascular disease prevention: The ADA has
      issued separate recommendations for each of the cardiovascular risk factors in
      patients with diabetes, and the AHA has shaped primary and secondary guidelines
      that extend to patients with diabetes. This statement will attempt to harmonize
      the recommendations of both organizations where possible but will recognize areas
      in which AHA and ADA recommendations differ.

PMID- 17192513
TI  - The common marmoset (Callithrix jacchus) has two very similar semenogelin genes
      as the result of gene conversion.
AB  - The semen coagulum proteins have undergone substantial structural changes during
      evolution. In primates, these seminal vesicle-secreted proteins are known as
      semenogelin I (SEMG1) and semenogelin II (SEMG2). Previous studies on the common
      marmoset (Callithrix jacchus) showed that ejaculated semen from this New World
      monkey contains semenogelin, but it remained unclear whether it carries both
      genes or only SEMG1 and no SEMG2, like the closely related cotton-top tamarin
      (Saguinus oedipus). In this study we show that there are two genes, both
      expressed in the seminal vesicles. Surprisingly, the genes show an almost perfect
      sequence identity in a region of 1.25 kb, encompassing nearly half of the genes
      and containing exon 1, intron 1, and the first 0.9 kb of exon 2. The underlying
      molecular mechanism is most likely gene conversion, and a phylogenetic analysis
      suggests that SEMG1 is the most probable donor gene. The marmoset SEMG1 in this
      report differs from a previously reported cDNA by a lack of nucleotides encoding
      one repeat of 60 amino acids, suggesting that marmoset SEMG1 displays allelic
      size variation. This is similar to what was recently demonstrated in humans, but
      in marmosets the polymorphism was generated by a repeat duplication, whereas in
      humans it was a deletion. Together, these studies shed new light on the evolution
      of semenogelins and the mechanisms that have generated the structural diversity
      of semen coagulum proteins.

PMID- 17192514
TI  - Oocyte-secreted factor activation of SMAD 2/3 signaling enables initiation of
      mouse cumulus cell expansion.
AB  - Expansion of the mouse cumulus-oocyte complex (COC) is dependent on oocyte
      secreted paracrine factors. Transforming growth factor beta (TGFB) superfamily
      molecules are prime candidates for the cumulus expansion-enabling factors
      (CEEFs), and we have recently determined that growth differentiation factor 9
      (GDF9) alone is not the CEEF. The aim of this study was to examine oocyte
      paracrine factors and their signaling pathways that regulate mouse cumulus
      expansion. Using RT-PCR, oocytes were found to express the two activin subunits,
      Inhba and Inhbb, and activin A and activin B both enabled FSH-induced cumulus
      expansion of oocytectomized (OOX) complexes. Follistatin, an activin-binding
      protein, neutralized activin-induced expansion but had no effect on oocyte
      induced expansion. The type I receptors for GDF9 and activin are activin receptor
      like kinase 5 (ALK5) and ALK4, respectively, both of which activate the same SMAD
      2/3 signaling pathway. We examined the requirement for this signaling system
      using an ALK 4/5/7 inhibitor, SB-431542. SB-431542 completely ablated FSH
      stimulated GDF9-, activin A-, activin B-, and oocyte-induced cumulus expansion.
      Moreover, SB-431542 also antagonized epidermal growth factor-stimulated, oocyte
      induced cumulus expansion. Using real-time RT-PCR, SB-431542 also attenuated GDF9
      , activin A-, and oocyte-induced OOX expression of hyaluronan synthase 2, tumor
      necrosis factor alpha-induced protein 6, prostaglandin synthase 2, and pentraxin
      3. This study provides evidence that the CEEF is composed of TGFB superfamily
      molecules that signal through SMAD 2/3 to enable the initiation of mouse cumulus
      expansion.

PMID- 17192515
TI  - Tilapia follicle-stimulating hormone (FSH): immunochemistry, stimulation by
      gonadotropin-releasing hormone, and effect of biologically active recombinant FSH
      on steroid secretion.
AB  - In fish, FSH is generally important for early gonadal development and
      vitellogenesis. As in mammals, FSH is a heterodimer composed of an alpha subunit
      that is noncovalently associated with the hormone-specific beta subunit. The
      objective of the present study was to express glycosylated, properly folded, and
      biologically active tilapia FSH (tFSH) using the Pichia pastoris expression
      system. Using this material, we aimed to develop a specific ELISA and to enable
      the study of FSH response to GnRH. The methylotrophic yeast P. pastoris was used
      to coexpress recombinant genes formed by fusion of mating factor alpha leader and
      tilapia fshb and cga coding sequences. Western blot analysis of tilapia pituitary
      FSH, resolved by SDS-PAGE, yielded a band of 15 kDa, while recombinant tFSH beta
      (rtFSH beta) and rtFSH beta alpha had molecular masses of 17-18 kDa and 26-30
      kDa, respectively. Recombinant tFSH beta alpha was found to bear only N-linked
      carbohydrates. Recombinant tFSH beta alpha significantly enhanced 11
      ketotestosterone (11-KT) and estradiol secretion from tilapia testes and ovaries,
      respectively, in a dose-dependent manner (similar to tilapia pituitary extract,
      affinity-purified pituitary FSH, and porcine FSH). Using antibodies raised
      against rtFSH beta, FSH-containing cells were localized adjacent to hypothalamic
      nerve fibers ramifying in the proximal pars distalis (PPD), while LH cells were
      localized in a more peripheral region of the PPD. Moreover, FSH is under the
      control of hypothalamic decapeptide GnRH, an effect that was abolished through
      the use of specific bioneutralizing antisera, anti-rtFSH beta. It also reduced
      basal secretion of 11-KT.

PMID- 17192517
TI  - My first 50 years of critical care (1956-2006).

PMID- 17192516
TI  - Infusion of exogenous tumor necrosis factor dose dependently alters the length of
      the luteal phase in cattle: differential responses to treatment with indomethacin
      and L-NAME, a nitric oxide synthase inhibitor.
AB  - We examined whether prostaglandins (PGs) and nitric oxide (NO) mediate tumor
      necrosis factor (TNF) actions in the estrus cycle. On Day 14 of the cycle, the
      following solutions were infused into the aorta abdominalis of a total of 51
      heifers (Experiments 1 and 2): saline; 1 or 10 microg of TNF; 480 mg indomethacin
      (INDO), an inhibitor of prostaglandin H synthase; 800 mg L-NAME, an inhibitor of
      NO synthase; and TNF (1 or 10 microg) in combination with INDO or L-NAME. TNF at
      1 microg infused directly into aorta abdominalis increased the level of
      PGF(2alpha) and decreased the level of progesterone (P4) in the peripheral blood
      and shortened the estrus cycle. The high TNF dose stimulated P4 and PGE(2) and
      prolonged the corpus luteum (CL) lifespan. INDO blocked the effects of both TNF
      doses on the CL lifespan and hormone output. L-NAME completely blocked the
      effects of the luteolytic TNF dose, whereas the effects of the luteotropic TNF
      dose were not inhibited. In Experiment 3 (Day 14), saline or different TNF doses
      were infused into the jugular vein (n = 9) or into the uterine lumen (n = 18).
      The CL lifespans of the different groups were not different when TNF was infused
      into the jugular vein. Although high TNF doses (1 and 10 microg) infused into the
      uterine lumen prolonged the CL lifespan, low doses (0.01 and 0.1 microg) induced
      premature luteolysis. We suggest that the actions of exogenous TNF on the CL
      lifespan depend on PG synthesis stimulated by TNF in the uterus. TNF at low
      concentrations initiates a positive cascade between uterine PGF(2alpha) and
      various luteolytic factors, including NO, to complete premature luteolysis.
      PGE(2) is a good candidate mediator of the luteotropic actions of exogenous TNF
      action.

PMID- 17192518
TI  - Questioning guidelines in the ECG Puzzler.

PMID- 17192519
TI  - In defense of the DNP.

PMID- 17192520
TI  - Questioning guidelines in the ECG Puzzler.

PMID- 17192521
TI  - Reader offers solution to blood pressure cuff problem.

PMID- 17192522
TI  - Confirmation of nasogastric tube placement.

PMID- 17192523
TI  - Evidence-based practice: use of the ventilator bundle to prevent ventilator
      associated pneumonia.
AB  - PURPOSE: To examine critical care nurses' knowledge about the use of the
      ventilator bundle to prevent ventilator-associated pneumonia. METHOD: Published
      reports were reviewed for current evidence on the use of the ventilator bundle to
      prevent ventilator-associated pneumonia, and education sessions were held to
      present the findings to 61 nurses in coronary care and surgical intensive care
      units. Changes in the nurses' knowledge were evaluated by using a 10-item test,
      given both before and after the sessions. Changes in the nurses' practices
      related to ventilator-associated pneumonia, including elevation of the head of
      the bed to 30 degrees to 45 degrees , were observed in 99 intubated patients.
      RESULTS: After the education sessions, the nurses performed better on 8 of the 10
      items tested (P from .03 to <.001). The areas of most significant improvement
      were elevation of the head of the bed (P < .001), charting of the elevation of
      the head of the bed (P= .009), oral care (P= .009), checking of the nasogastric
      tube for residual volume (P = .008), washing of hands before contact with
      patients (P < .001), and limiting the wearing of rings (P < .001) and nail polish
      (P = .04). Even after the education sessions, the nurses' compliance with hand
      washing recommendations before contact with patients was low, though
      statistically some improvement was apparent. Contraindications to elevation of
      the head of the bed did not appear to affect the nurses' practices (P= .38).
      CONCLUSION: Education sessions designed to inform nurses about the ventilator
      bundle and its use to prevent ventilator-associated pneumonia have a significant
      effect on participants' knowledge and subsequent clinical practice.

PMID- 17192524
TI  - Nurses' implementation of guidelines for ventilator-associated pneumonia from the
      Centers for Disease Control and Prevention.
AB  - BACKGROUND: Ventilator-associated pneumonia accounts for 47% of infections in
      patients in intensive care units. Adherence to the best nursing practices
      recommended in the 2003 guidelines for the prevention of ventilator-associated
      pneumonia from the Centers for Disease Control and Prevention should reduce the
      risk of ventilator-associated pneumonia. OBJECTIVE: To evaluate the extent to
      which nurses working in intensive care units implement best practices when
      managing adult patients receiving mechanical ventilation. METHODS: Nurses
      attending education seminars in the United States completed a 29-item
      questionnaire about the type and frequency of care provided. RESULTS: Twelve
      hundred nurses completed the questionnaire. Most (82%) reported compliance with
      hand-washing guidelines, 75% reported wearing gloves, half reported elevating the
      head of the bed, a third reported performing subglottic suctioning, and half
      reported having an oral care protocol in their hospital. Nurses in hospitals with
      an oral care protocol reported better compliance with hand washing and
      maintaining head-of-bed elevation, were more likely to regularly provide oral
      care, and were more familiar with rates of ventilator-associated pneumonia and
      the organisms involved than were nurses working in hospitals without such
      protocols. CONCLUSIONS: The guidelines for the prevention of ventilator
      associated pneumonia from the Centers for Disease Control and Prevention are not
      consistently or uniformly implemented. Practices of nurses employed in hospitals
      with oral care protocols are more often congruent with the guidelines than are
      practices of nurses employed in hospitals without such protocols. Significant
      reductions in rates of ventilator-associated pneumonia may be achieved by broader
      implementation of oral care protocols.

PMID- 17192525
TI  - Packed red blood cell transfusion in the intensive care unit: limitations and
      consequences.
AB  - OBJECTIVE: To review the literature on the limitations and consequences of packed
      red blood cell transfusions, with particular attention to critically ill
      patients. METHODS: The PubMed database of the National Library of Medicine was
      searched to find published articles on the indications, clinical utility,
      limitations, and consequences of red blood cell transfusion, especially in
      critically ill patients. RESULTS: Several dozen papers were reviewed, including
      case series, meta-analyses, and retrospective and prospective studies evaluating
      the physiological effects, clinical efficacy, and consequences and complications
      of transfusion of packed red blood cells. Most available data indicate that
      packed red blood cells have a very limited ability to augment oxygen delivery to
      tissues. In addition, the overwhelming preponderance of data accumulated in the
      past decade indicate that patients receiving such transfusions have significantly
      poorer outcomes than do patients not receiving such transfusions, as measured by
      a variety of parameters including, but not limited to, death and infection.
      CONCLUSIONS: According to the available data, transfusion of packed red blood
      cells should be reserved only for situations in which clear physiological
      indicators for transfusion are present.

PMID- 17192526
TI  - Rotational bed therapy to prevent and treat respiratory complications: a review
      and meta-analysis.
AB  - BACKGROUND: Immobility is associated with complications involving many body
      systems. OBJECTIVE: To review the effect of rotational therapy (use of
      therapeutic surfaces that turn on their longitudinal axes) on prevention and/or
      treatment of respiratory complications in critically ill patients. METHODS:
      Published articles evaluating prophylaxis and/or treatment were reviewed.
      Prospective randomized controlled trials were assessed for quality and included
      in meta-analyses. RESULTS: A literature search yielded 15 nonrandomized,
      uncontrolled, or retrospective studies. Twenty prospective randomized controlled
      trials on rotational therapy were published between 1987 and 2004. Various types
      of beds were studied, but few details on the rotational parameters were reported.
      The usual control was manual turning of patients by nurses every 2 hours. One
      animal investigation and 12 clinical trials addressed the effectiveness of
      rotational therapy in preventing respiratory complications. Significant benefits
      were reported in the animal study and 4 of the trials. Significant benefits to
      patients were reported in 2 of another 4 studies focused on treatment of
      established complications. Researchers have examined the effects of rotational
      therapy on mucus transport, intrapulmonary shunt, hemodynamic effects, urine
      output, and intracranial pressure. Little convincing evidence is available,
      however, on the most effective rotation parameters (eg, degree, pause time, and
      amount of time per day). Meta-analysis suggests that rotational therapy decreases
      the incidence of pneumonia but has no effect on duration of mechanical
      ventilation, number of days in intensive care, or hospital mortality.
      CONCLUSIONS: Rotational therapy may be useful for preventing and treating
      respiratory complications in selected critically ill patients receiving
      mechanical ventilation.

PMID- 17192527
TI  - Discriminating between right coronary artery and circumflex artery occlusion by
      using a noninvasive 18-lead electrocardiogram.
AB  - BACKGROUND: Differentiating occlusion of the circumflex branch of the left
      coronary artery (also called the circumflex artery) from occlusion of the right
      coronary artery is often difficult because either may be associated with a
      pattern of acute inferior myocardial infarction on the electrocardiogram.
      OBJECTIVES: To determine if an inexpensive 18-lead electrocardiogram can provide
      useful information in differentiating sites of coronary occlusion. METHODS:
      Continuous 18-lead electrocardiograms, including standard 12-lead, right
      ventricular, and posterior leads, were recorded in 38 and 50 subjects undergoing
      percutaneous coronary interventions in the right coronary artery and the
      circumflex artery, respectively. RESULTS: ST-segment elevation in the posterior
      leads was twice as frequent during occlusion of the circumflex artery as during
      right coronary occlusion (P < .001). ST-segment elevation in the right
      ventricular leads and inferior leads occurred more often during occlusion of the
      right coronary artery than during occlusion of the circumflex artery. ST-segment
      depression in lead aVL is highly suggestive of right coronary occlusion, whereas
      ST-segment elevation in posterior leads without depression of the ST segment in
      lead aVL is highly sensitive and specific for occlusion of the circumflex artery.
      CONCLUSIONS: ST-segment changes in the 18-lead electrocardiogram can be used to
      differentiate between occlusions of the circumflex artery and occlusions of the
      right coronary artery. Knowing which vessel is occluded before percutaneous
      coronary intervention can help in planning the procedure and recognizing when
      patients are at high risk for disturbances in conduction at the atrioventricular
      node.

PMID- 17192528
TI  - Psychosocial issues for patients with ventricular assist devices: a qualitative
      pilot study.
AB  - BACKGROUND: Surgical implantation of a ventricular assist device is being used
      increasingly in patients in the United Kingdom, yet few studies have focused on
      patients' experiences from a phenomenological (psychological) perspective.
      OBJECTIVE: To explore, through a pilot study, the impact of implantation of a
      ventricular assist device on patients' bodies and lives. METHODS: This
      qualitative retrospective study included 6 patients (4 men and 2 women) and 3 of
      these patients' relatives. Patients were from 17 to 50 years old and had used
      Thoratec, Heartmate, or VentrAssist devices. RESULTS: The participants' accounts
      clustered around a number of themes, 2 of which are reported here: (1) body and
      self and (2) trust. Each theme comprised several subthemes: body and self had sub
      themes of shock, restrictions, scarring, and infection; trust had subthemes of
      keeping me alive, device failure, and confidence. CONCLUSIONS: The ventricular
      assist device has a considerable effect on a patient's body and sense of self.
      This effect is often accommodated without much difficulty, but some patients and
      their families need additional psychological support during and after use of a
      ventricular assist device. Assessment before implantation of such a device can
      sometimes reveal this need, but such assessment may not be possible in emergency
      procedures. Trusting the new heart or the native recovered heart may be difficult
      for some patients. Further research is needed to understand this phenomenon.

PMID- 17192529
TI  - Propofol infusion syndrome: a case of increasing morbidity with traumatic brain
      injury.
AB  - A previously healthy 16-year-old boy with a closed, severe traumatic brain injury
      was admitted to a surgical and trauma intensive care unit. He was given a
      continuous infusion of propofol for sedation and to control intracranial
      pressure. About 3 days after the propofol infusion was started, metabolic
      acidosis and rhabdomyolysis developed. Acute renal failure ensued as a result of
      the rhabdomyolysis. Tachycardia with wide QRS complexes developed without
      hyperkalemia. The patient died of refractory cardiac dysrhythmia and circulatory
      collapse approximately 36 hours after the first signs of propofol infusion
      syndrome appeared. Propofol infusion syndrome is a rare but frequently fatal
      complication in critically ill children who are given prolonged high-dose
      infusions of the drug. The syndrome is characterized by severe metabolic
      acidosis, rhabdomyolysis, acute renal failure, refractory myocardial failure, and
      hyperlipidemia. Despite several publications on the subject in the past decade,
      most cases still seem to remain undetectable.

PMID- 17192530
TI  - Healing environments and the limits of empirical evidence.

PMID- 17192531
TI  - Electrocardiographic artifacts.

PMID- 17192533
TI  - Images in clinical medicine. Adults with osteogenesis imperfecta.

PMID- 17192532
TI  - Evaluating pacemaker function with full disclosure.

PMID- 17192534
TI  - Uncovering an epidemic--screening for mental illness in teens.

PMID- 17192535
TI  - Familial pathways to suicidal behavior--understanding and preventing suicide
      among adolescents.

PMID- 17192536
TI  - The antidepressant quandary--considering suicide risk when treating adolescent
      depression.

PMID- 17192537
TI  - An intervention to decrease catheter-related bloodstream infections in the ICU.
AB  - BACKGROUND: Catheter-related bloodstream infections occurring in the intensive
      care unit (ICU) are common, costly, and potentially lethal. METHODS: We conducted
      a collaborative cohort study predominantly in ICUs in Michigan. An evidence-based
      intervention was used to reduce the incidence of catheter-related bloodstream
      infections. Multilevel Poisson regression modeling was used to compare infection
      rates before, during, and up to 18 months after implementation of the study
      intervention. Rates of infection per 1000 catheter-days were measured at 3-month
      intervals, according to the guidelines of the National Nosocomial Infections
      Surveillance System. RESULTS: A total of 108 ICUs agreed to participate in the
      study, and 103 reported data. The analysis included 1981 ICU-months of data and
      375,757 catheter-days. The median rate of catheter-related bloodstream infection
      per 1000 catheter-days decreased from 2.7 infections at baseline to 0 at 3 months
      after implementation of the study intervention (P< or =0.002), and the mean rate
      per 1000 catheter-days decreased from 7.7 at baseline to 1.4 at 16 to 18 months
      of follow-up (P<0.002). The regression model showed a significant decrease in
      infection rates from baseline, with incidence-rate ratios continuously decreasing
      from 0.62 (95% confidence interval [CI], 0.47 to 0.81) at 0 to 3 months after
      implementation of the intervention to 0.34 (95% CI, 0.23 to 0.50) at 16 to 18
      months. CONCLUSIONS: An evidence-based intervention resulted in a large and
      sustained reduction (up to 66%) in rates of catheter-related bloodstream
      infection that was maintained throughout the 18-month study period.

PMID- 17192538
TI  - Lapatinib plus capecitabine for HER2-positive advanced breast cancer.
AB  - BACKGROUND: Lapatinib, a tyrosine kinase inhibitor of human epidermal growth
      factor receptor type 2 (HER2, also referred to as HER2/neu) and epidermal growth
      factor receptor (EGFR), is active in combination with capecitabine in women with
      HER2-positive metastatic breast cancer that has progressed after trastuzumab
      based therapy. In this trial, we compared lapatinib plus capecitabine with
      capecitabine alone in such patients. METHODS: Women with HER2-positive, locally
      advanced or metastatic breast cancer that had progressed after treatment with
      regimens that included an anthracycline, a taxane, and trastuzumab were randomly
      assigned to receive either combination therapy (lapatinib at a dose of 1250 mg
      per day continuously plus capecitabine at a dose of 2000 mg per square meter of
      body-surface area on days 1 through 14 of a 21-day cycle) or monotherapy
      (capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of
      a 21-day cycle). The primary end point was time to progression, based on an
      evaluation by independent reviewers under blinded conditions. RESULTS: The
      interim analysis of time to progression met specified criteria for early
      reporting on the basis of superiority in the combination-therapy group. The
      hazard ratio for the independently assessed time to progression was 0.49 (95%
      confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination
      therapy group and 72 events in the monotherapy group. The median time to
      progression was 8.4 months in the combination-therapy group as compared with 4.4
      months in the monotherapy group. This improvement was achieved without an
      increase in serious toxic effects or symptomatic cardiac events. CONCLUSIONS:
      Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2
      positive advanced breast cancer that has progressed after treatment with regimens
      that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov
      number, NCT00078572 [ClinicalTrials.gov].).

PMID- 17192539
TI  - Female predominance and transmission distortion in the long-QT syndrome.
AB  - BACKGROUND: Congenital long-QT syndrome is a disorder resulting in ventricular
      arrhythmias and sudden death. The most common forms of the long-QT syndrome,
      types 1 and 2, are caused by mutations in the potassium-channel genes KCNQ1 and
      KCNH2, respectively. Although inheritance of the long-QT syndrome is autosomal
      dominant, female predominance has often been observed and has been attributed to
      an increased susceptibility to cardiac arrhythmias in women. We investigated the
      possibility of an unbalanced transmission of the deleterious trait. METHODS: We
      investigated the distribution of alleles for the long-QT syndrome in 484 nuclear
      families with type 1 disease and 269 nuclear families with type 2 disease, all
      with fully genotyped offspring. The families were recruited in five European
      referral centers for the long-QT syndrome. Mutation segregation, sex ratio, and
      parental transmission were analyzed after correction for single ascertainment.
      RESULTS: Classic mendelian inheritance ratios were not observed in the offspring
      of either female carriers of the long-QT syndrome type 1 or male and female
      carriers of the long-QT syndrome type 2. Among the 1534 descendants, the
      proportion of genetically affected offspring was significantly greater than that
      expected according to mendelian inheritance: 870 were carriers of a mutation
      (57%), and 664 were noncarriers (43%, P<0.001). Among the 870 carriers, the
      allele for the long-QT syndrome was transmitted more often to female offspring
      (476 [55%]) than to male offspring (394 [45%], P=0.005). Increased maternal
      transmission of the long-QT syndrome mutations to daughters was also observed,
      possibly contributing to the excess of female patients with autosomal dominant
      long-QT syndrome. CONCLUSIONS: Positive selection of the mutated alleles that
      cause the long-QT syndrome leads to transmission distortion, with increased
      proportions of mutation carriers among the offspring of affected families.
      Alleles for the long-QT syndrome are more often transmitted to daughters than to
      sons.

PMID- 17192540
TI  - Human Trypanosoma evansi infection linked to a lack of apolipoprotein L-I.
AB  - Humans have innate immunity against Trypanosoma brucei brucei that is known to
      involve apolipoprotein L-I (APOL1). Recently, a case of T. evansi infection in a
      human was identified in India. We investigated whether the APOL1 pathway was
      involved in this occurrence. The serum of the infected patient was found to have
      no trypanolytic activity, and the finding was linked to the lack of APOL1, which
      was due to frameshift mutations in both APOL1 alleles. Trypanolytic activity was
      restored by the addition of recombinant APOL1. The lack of APOL1 explained the
      patient's infection with T. evansi.

PMID- 17192541
TI  - Deficiency of cartilage-associated protein in recessive lethal osteogenesis
      imperfecta.
AB  - Classic osteogenesis imperfecta, an autosomal dominant disorder associated with
      osteoporosis and bone fragility, is caused by mutations in the genes for type I
      collagen. A recessive form of the disorder has long been suspected. Since the
      loss of cartilage-associated protein (CRTAP), which is required for post
      translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in
      mice, we investigated whether CRTAP deficiency is associated with recessive
      osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis
      imperfecta, who did not have a primary collagen defect yet had excess post
      translational modification of collagen, were found to have a recessive condition
      resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I
      collagen is important for bone formation.

PMID- 17192542
TI  - Clinical practice. Monoclonal gammopathy of undetermined significance.

PMID- 17192543
TI  - Images in clinical medicine. Benign diffuse breast hyperplasia during pregnancy.

PMID- 17192544
TI  - Case records of the Massachusetts General Hospital. Case 40-2006. A 64-year-old
      man with anemia and a low level of HDL cholesterol.

PMID- 17192545
TI  - Team-based prevention of catheter-related infections.

PMID- 17192546
TI  - Targeted therapy for metastatic breast cancer.

PMID- 17192547
TI  - Eculizumab in paroxysmal nocturnal hemoglobinuria.

PMID- 17192548
TI  - Enoxaparin in elective percutaneous coronary intervention.

PMID- 17192549
TI  - Echinocandins for candidemia.

PMID- 17192550
TI  - Acute vulvovaginitis.

PMID- 17192551
TI  - Effects of dietary nitrate on blood pressure in healthy volunteers.

PMID- 17192552
TI  - Chronology of advances in neuroendocrine immunomodulation.
AB  - This review documents the remarkable progress over the last 50 years of our
      knowledge of the control of anterior pituitary hormone release and synthesis by a
      family of peptidic releasing and inhibiting hormones, synthesized in hypothalamic
      neurons and released into the hypophysial portal vessels. These vessels transport
      them to the anterior pituitary, where they stimulate release and synthesis of
      pituitary hormones or inhibit these processes. In general, there are at least two
      hypothalamic hormones for each pituitary hormone-vasopressin and corticotrophin
      releasing hormone (CRH) for adrenocorticotropin hormone (ACTH) and growth hormone
      releasing hormone (GHRH) and growth hormone-inhibiting hormone (GIH) for growth
      hormone (GH). Some of these hormones have extrapituitary action: for example,
      luteinizing hormone-releasing hormone (LHRH) stimulates mating behavior. High
      doses of LHRH have an inhibitory action on the growth of prostate cancer.
      Proinflammatory and anti-inflammatory cytokines act not only in the brain, but
      also on the pituitary and peripheral tissues. All of these transmitters are
      controlled by neuronal transmitters. We anticipate further rapid progress and
      clinical application of these transmitters and the discovery of new ones.

PMID- 17192553
TI  - The mitochondrion as a primary site of action of regulatory agents involved in
      neuroimmunomodulation.
AB  - A major system of neuroimmunomodulation is the hypothalamic-pituitary
      adrenocortical (HPA) axis, acting through glucocorticoids and their intracellular
      signaling components, exerting both stimulatory and inhibitory effects on the
      immune reaction. Glucocorticoids inhibit the production of proinflammatory
      cytokines by interacting with nuclear transcription factors (nuclear factor [NF]
      kappaB, activated protein [AP]-1) and induce the production of several anti
      inflammatory cytokines by gene activation. In some cells and/or in extreme stress
      conditions, apoptosis is evoked. In most processes related to
      neuroimmunomodulation a prominent role is emerging for mitochondria. These
      organelles generate more than 90% of the cell's energy requirements through
      oxidative phosphorylation (OXPHOS), which is regulated by several agents,
      including steroid and thyroid hormones. These hormones are inducers of nuclear
      and mitochondrial OXPHOS gene transcription and they exert a primary action not
      only on nuclear but also on mitochondrial genes by way of cognate receptors.
      Recently, additional nuclear transcription factors involved in
      neuroimmunomodulation have been detected in mitochondria (NF-kappaB, AP-1, p53,
      calcium/cAMP response element binding protein [CREB]), and binding sites of these
      and putative binding sites of other nuclear transcription factors have been
      identified in the mitochondrial genome. The interaction of these factors with
      mitochondrial regulatory proteins, with receptors and with the genome has been
      shown and, in some cases, modulation of mitochondrial transcription was observed
      with possible effects on energy yield. The mitochondria store a host of critical
      apoptotic activators and inhibitors in their intermembrane space and the release
      of these factors could be another possible mode of action of the mitochondrially
      translocated regulatory agents and receptors.

PMID- 17192554
TI  - Immunomodulatory properties of substance P: the gastrointestinal system as a
      model.
AB  - Communication between nerves and immune and inflammatory cells of the small and
      large intestine plays a major role in the modulation of several intestinal
      functions, including intestinal motility, ion transport, and mucosal
      permeability. Neuroimmune interactions at intestinal sites have been associated
      with the pathophysiology of infectious and enterotoxin-mediated diarrhea and
      intestinal inflammation, including inflammatory bowel disease (IBD). During the
      past 20 years the neuropeptide substance P (SP) has been identified as an
      important mediator in the development and progress of intestinal inflammation by
      binding to its high-affinity neurokinin-1 receptor (NK-1R). This peptide,
      released from enteric nerves, sensory neurons, and inflammatory cells of the
      lamina propria during intestinal inflammation, participates in gut inflammation
      by interacting, directly or indirectly, with NK-1R expressed on nerves,
      epithelial cells, and immune and inflammatory cells, such as mast cells,
      macrophages, and T cells. SP-dependent activation of these cells leads to the
      release of cytokines and chemokines as well as other neuropeptides that modulate
      diarrhea, inflammation, and motility associated with the pathophysiology of
      several intestinal disease states. The recent development of specific nonpeptide
      NK-1R antagonists and NK-1R-deficient mice helped us understand the functional
      importance of the SP-NK-1R system in mediating intestinal neuroimmune
      interactions and to identify the particular cells and signaling pathways involved
      in this response. This review summarizes our understanding on the
      immunomodulatory properties of SP and its receptor in the intestinal tract with
      particular focus on their involvement in intestinal physiology as well as in the
      pathophysiology of several intestinal disease states at the in vivo and cell
      signaling level.

PMID- 17192555
TI  - Hypothalamic-pituitary-adrenal axis function in Sjogren's syndrome: mechanisms of
      neuroendocrine and immune system homeostasis.
AB  - To date, evidence suggests that rheumatic diseases are associated with
      hypofunctioning of the hypothalamic-pituitary-adrenal (HPA) axis. Sjogren's
      syndrome (SS), the second most common autoimmune disorder, is characterized by
      diminished lacrimal and salivary gland secretion. To examine HPA axis activity in
      SS patients, the adrenocorticotropin (ACTH) response to ovine corticotropin
      releasing factor (oCRH) was used as a direct measure of corticotrophic function,
      and the plasma cortisol response to the ACTH released during oCRH stimulation as
      an indirect measure of adrenal function. Significantly lower basal ACTH and
      cortisol levels were found in patients with SS and were associated with a blunted
      pituitary and adrenal response to oCRH compared to normal controls. Fibromyalgia
      (FM) patients demonstrated elevated evening basal ACTH and cortisol levels and a
      somewhat exaggerated peak, delta, and net integrated ACTH response to oCRH. A
      subgroup of SS patients also met the diagnostic criteria for FM and demonstrated
      a pituitary-adrenal response that was intermediate to SS and FM. These findings
      suggest not only adrenal axis hypoactivity in SS and FM patients, but also that
      varying patterns of adrenal and thyroid axes dysfunction may exist in patients
      with different rheumatic diseases.

PMID- 17192556
TI  - The role of chaperone proteins in autoimmunity.
AB  - Heat-shock or stress proteins (HSPs) are intracellular molecules that are
      expressed under cellular stress and have housekeeping and cytoprotective
      functions. Many of them act also as molecular chaperones, assisting the correct
      folding, stabilization, and translocation of proteins. In pathological
      situations, such as necrotic cell death, they can be released into the
      extracellular environment complexed with intact or fragmented cellular proteins.
      Evidence is now accumulating to indicate that, under certain circumstances, these
      complexes can contribute to induction of autoimmunity by receptor-mediated
      activation of the innate immune response (signaling the "danger") and by
      participation in the presentation of autoantigens for the adaptive immune
      response (acting as natural adjuvants). In addition, the conservation of HSPs
      through prokaryotes and eukaryotes, together with the increased production of
      host and microbial HSPs at the site of infection, has led to the proposition that
      these proteins may provide a link between infection and autoimmunity. This review
      outlines the mechanisms for the potential involvement of chaperones in the
      induction of autoimmune disease.

PMID- 17192557
TI  - The role of stress in asthma: insight from studies on the effect of acute and
      chronic stressors in models of airway inflammation.
AB  - Asthma, a chronic inflammatory disease of the airways, is greatly influenced by
      psychosocial factors and stress. This review looks at clinical studies that have
      shown strong associations between psychological stress and asthma to identify
      potential mechanisms for these interactions. Furthermore, we review animal
      studies involving stress and airway inflammation or airway hyperresponsiveness,
      and discuss possible mechanisms of stress action in asthma. In conclusion,
      further research, both in humans and in animal models, into the mechanisms of
      stress-induced changes in asthma exacerbation are required to help better
      understand the complex makeup of asthma and assist in the development of
      therapies directed at the interplay between the nervous system and airway
      inflammation.

PMID- 17192558
TI  - The critical role of mast cells in allergy and inflammation.
AB  - Mast cells are well known for their involvement in allergic and anaphylactic
      reactions, but recent findings implicate them in a variety of inflammatory
      diseases affecting different organs, including the heart, joints, lungs, and
      skin. In these cases, mast cells appear to be activated by triggers other than
      aggregation of their IgE receptors (FcepsilonRI), such as anaphylatoxins,
      immunoglobulin-free light chains, superantigens, neuropeptides, and cytokines
      leading to selective release of mediators without degranulation. These findings
      could explain inflammatory diseases, such as asthma, atopic dermatitis, coronary
      inflammation, and inflammatory arthritis, all of which worsen by stress. It is
      proposed that the pathogenesis of these diseases involve mast cell activation by
      local release of corticotropin-releasing hormone (CRH) or related peptides.
      Combination of CRH receptor antagonists and mast cell inhibitors may present
      novel therapeutic interventions.

PMID- 17192559
TI  - Immunomodulation: the future cure for allergic diseases.
AB  - Allergies are the result of aberrant immune reactivity against common innocuous
      environmental proteins (allergens). A pivotal component of allergic pathogenesis
      is the generation of allergen-specific Th cells with an effector phenotype. These
      Th cells activate a complex immune cascade that triggers the release of potent
      mediators and enhances the mobilization of several inflammatory cells types,
      which in turn elicit the acute allergic reactions and promote the development of
      chronic inflammation. The current therapies for allergic diseases focus primarily
      on pharmacological control of symptoms and suppression of inflammation. This
      approach is beneficial, but not curative, since the underlying immune pathology
      is not inhibited. In an attempt to develop more effective therapeutic strategies,
      the scientific interest has been directed toward methods down-modulating the
      immune mechanisms that initiate and maintain the allergic cascade. Today, the
      only widely used disease-modifying form of allergy treatment is the specific
      immunotherapy with allergen extracts. More recently the use of anti-IgE has been
      approved for patients with allergic asthma. Other immunomodulatory methods being
      currently explored are the administration of microbial adjuvants that inhibit Th2
      reactivity and the design of molecules that interrupt the activity of key
      allergic cytokines, chemokines, or other Th2 effector mediators.

PMID- 17192560
TI  - Neural correlates of IgE-mediated allergy.
AB  - Although many authors have considered a direct interaction between allergic
      reactions and behavioral changes, supporting evidence has been elusive. In this
      series of studies we show that after oral or nasal ovalbumin (OVA) challenge,
      allergic mice present increased Fos expression in the paraventricular nucleus of
      the hypothalamus (PVN) and in the central nucleus of the amygdala (CeA). Mice
      with food allergy display higher levels of anxiety and increased serum
      corticosterone levels, and allergy-activated neurons express corticotropin
      releasing factor (CRF) in the PVN and CeA. OVA-allergic mice develop aversion to
      an antigen-containing solution, and also avoid a dark compartment previously
      associated with nebulized OVA. Results on brain Fos expression and behavioral
      data seem compatible with adaptive responses. Removal of IgE by either antibody
      depletion or the development of oral tolerance precluded all responses analyzed
      here. C-sensitive fiber destruction by neonatal capsaicin inhibited the
      activation in the PVN, but not in the CeA, and decreased the magnitude of food
      aversion. Cromolyn, a mast cell stabilizer, completely blocked Fos expression in
      the PVN and CeA, and precluded the development of aversion to the dark
      compartment associated with nebulized OVA. Employing mice that do not develop an
      important inflammatory infiltrate following nasal OVA challenge, we found that
      inflammatory cells are not required at the site of challenge in order to trigger
      neural or behavioral correlates of murine experimental asthma. Altogether, we
      have built a solid foundation for understanding neuroimmune interactions during
      allergic responses that may contribute to the comprehension of psychological
      disorders associated with allergy.

PMID- 17192561
TI  - Dialogue between the brain and the immune system in inflammatory arthritis.
AB  - The crosstalk between the brain and the immune system in inflammatory arthritis
      is exerted mainly through the activation or downregulation of the hypothalamic
      pituitary-adrenal (HPA), the hypothalamic-pituitary-gonadal (HPG), and the
      hypothalamic-autonomic nervous system (HANS) axes. In this review, we will
      present an overview of the most recent data regarding the regulation of these
      complex pathways of neuroendocrine response during the different phases of
      inflammatory arthritides such as rheumatoid arthritis (RA). Furthermore, the
      effect of the most recently available biologic therapies like anti-tumor necrosis
      factor (TNF-a) on the neuroendocrine function in patients with RA will be
      reviewed.

PMID- 17192562
TI  - Neurosteroids as endogenous inhibitors of neuronal cell apoptosis in aging.
AB  - The neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester DHEAS,
      and allopregnanolone (Allo) are produced in the adrenals and the brain. Their
      production rate and levels in serum, brain, and adrenals decrease gradually with
      advancing age. The decline of their levels was associated with age-related
      neuronal dysfunction and degeneration, most probably because these steroids
      protect central nervous system (CNS) neurons against noxious agents. Indeed,
      DHEA(S) protects rat hippocampal neurons against NMDA-induced excitotoxicity,
      whereas Allo ameliorates NMDA-induced excitotoxicity in human neurons. These
      steroids exert also a protective role on the sympathetic nervous system. Indeed,
      DHEA, DHEAS, and Allo protect chromaffin cells and the sympathoadrenal PC12 cells
      (an established model for the study of neuronal cell apoptosis and survival)
      against serum deprivation-induced apoptosis. Their effects are time- and dose
      dependent with EC(50) 1.8, 1.1, and 1.5 nM, respectively. The prosurvival effect
      of DHEA(S) appears to be NMDA-, GABA(A)- sigma1-, or estrogen receptor
      independent, and is mediated by G-protein-coupled-specific membrane binding
      sites. It involves the antiapoptotic Bcl-2 proteins, and the activation of
      prosurvival transcription factors CREB and NF-kappaB, upstream effectors of the
      antiapoptotic Bcl-2 protein expression, as well as prosurvival kinase
      PKCalpha/beta, a posttranslational activator of Bcl-2. Furthermore, they directly
      stimulate biosynthesis and release of neuroprotective catecholamines, exerting a
      direct transcriptional effect on tyrosine hydroxylase, and regulating actin
      depolymerization and submembrane actin filament disassembly, a fast-response
      cellular system regulating trafficking of catecholamine vesicles. These findings
      suggest that neurosteroids may act as endogenous neuroprotective factors. The
      decline of neurosteroid levels during aging may leave the brain unprotected
      against neurotoxic challenges.

PMID- 17192563
TI  - Role of thymulin or its analogue as a new analgesic molecule.
AB  - The thymic peptide thymulin is known for its immunomodulatory role. However,
      several recent reports have indicated that thymulin is capable of interacting
      directly and/or indirectly with the nervous system. One of the first lines of
      evidence of this interaction was obtained in a series of experiments showing the
      hyperalgesic actions of this peptide. We demonstrated that, at low doses (ng),
      local (intraplantar) or systemic (intraperitoneal) injections of thymulin
      resulted in hyperalgesia with an increase in proinflammatory mediators, and that
      this peptide could act directly on the afferent nerve terminals through
      prostaglandin-E2 (PGE2)-dependent mechanisms, thus forming a neuroimmune loop
      involving capsaicin-sensitive primary afferent fibers. In further experiments,
      systemic injections of relatively high doses (1-25 microg) of thymulin or of an
      analogue peptide (PAT) deprived of hyperalgesic effect, have been shown to reduce
      the inflammatory pain and the upregulated levels of cytokines induced by
      endotoxin (ET) injection. In addition, PAT treatment appeared to alleviate the
      sickness behavior (motor behavior and fever) induced by systemic inflammation.
      These effects could be attributed, at least partly, to the downregulation of
      proinflammatory mediators. Furthermore, when compared with the effects of other
      anti-inflammatory drugs, PAT exerted equal or even stronger analgesic effects,
      and at much lower concentrations. Subsequent experiments were designed to examine
      the effects of intracerebroventricular (i.c.v.) injections of thymulin on
      cerebral inflammation induced by i.c.v. injection of ET. Pretreatment with
      thymulin reduced, in a dose-dependent manner, the ET-induced hyperalgesia, and
      exerted differential effects on the upregulated levels of cytokines in different
      areas of the brain, suggesting a neuroprotective role for thymulin in the central
      nervous system (CNS). Preliminary results demonstrate that thymulin inhibits in
      the hippocampus the ET-induced nuclear activation of NF-kappaB, the transcription
      factor required for the expression of proinflammatory cytokines genes. Although
      the mechanism of action of these molecules is not totally elucidated, our results
      indicate a possible therapeutic use of thymulin or PAT as analgesic and anti
      inflammatory drugs.

PMID- 17192564
TI  - Therapeutic management of chronic neuropathic pain: an examination of
      pharmacologic treatment.
AB  - Neuropathic pain is defined as pain caused by a lesion in the nervous system and
      is common in clinical practice. Diagnosis can be difficult. Recommendations for
      first-line pharmacologic treatments are based on positive results from multiple,
      randomized, controlled trials, and recommendations for second-line pharmacologic
      treatments are based on the positive result of a single, randomized, controlled
      trial or inconsistent results of multiple, randomized, controlled trials. The
      results of published trials and clinical experience provide the foundation for
      specific recommendations for first-line treatments, which include gabapentin, 5%
      lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic
      antidepressants (TCAs). Gabapentin (up to 3,600 mg/day) significantly reduced
      pain compared with placebo; improvements in sleep, mood, and quality of life were
      also demonstrated. Adverse effects of gabapentin include somnolence and
      dizziness, and, less commonly, gastrointestinal symptoms and mild peripheral
      edema. Thus, monitoring and dosage adjustment are required, without
      discontinuation of the drug. Gabapentin combined with morphine achieved better
      analgesia at lower doses of each drug than each drug alone, with only mild
      adverse effects. The first medication that proved effective for neuropathic pain
      in placebo-controlled trials was TCAs. Treatment decisions for patients with
      neuropathic pain can be difficult. Interest in the mechanisms and treatment of
      chronic neuropathic pain has increased during the past years, resulting in
      significant treatment advances in the future. In this article all recent
      knowledge on therapeutic management of chronic neuropathic pain is presented.

PMID- 17192565
TI  - Regulation of dendritic cell differentiation by vasoactive intestinal peptide:
      therapeutic applications on autoimmunity and transplantation.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs)
      involved in the defense of the body and in the maintenance of the immune
      tolerance. The regulation of their maturation, migration, and expression of
      stimulatory and costimulatory molecules has major consequences on the immune
      response. The endogenous factors that regulate DC function are poorly known.
      Vasoactive intestinal peptide (VIP) is a neuropeptide with potent anti
      inflammatory actions. This anti-inflammatory profile is maintained partially
      through effects on DC differentiation/function. Thus, VIP has differential
      effects on DCs, depending on the differentiation and stimulatory states. Immature
      DCs treated with VIP exhibit increased CD86 expression and induce CD4(+) T cell
      proliferation. In addition, the CD4(+) T cells activated in vitro or in vivo by
      VIP-treated iDCs exhibit a Th2 phenotype. In contrast, VIP reduces both CD86 and
      CD80 expression on lipopolysaccharide (LPS)-stimulated DCs, and inhibits the
      capacity of DCs to induce in vitro or in vivo T cell proliferation. However,
      addition of VIP in the early states of DC differentiation results in the
      generation of DCs that cannot mature following inflammatory stimuli that exhibit
      a tolerogenic phenotype, characterized by low expression of costimulatory
      molecules (CD40, CD80, and CD86), low production of proinflammatory cytokines,
      increased production of IL-10, and capacity to induce regulatory T cells with
      suppressive actions. The effect of VIP on the DC-Treg axis represents an
      additional mechanism for their general anti-inflammatory role, particularly
      relevant in autoimmunity and transplantation.

PMID- 17192566
TI  - Neuroendocrine regulation of skin dendritic cells.
AB  - It has long been postulated that stress can affect certain skin conditions, and
      there is increasing experimental evidence that the neuroendocrine system can
      directly participate in cutaneous inflammation. Neurohormones, such as
      glucocorticoids and catecholamines, can reach the skin through the bloodstream
      after activation of the hypothalamic-pituitary-adrenal axis and the sympathetic
      nervous system, respectively. Multiple neuropeptides, among them calcitonin gene
      related peptide, alpha-melanocyte stimulating hormone, pituitary adenylate
      cyclase-activating peptide, substance P, vasoactive intestinal peptide, and
      norepinephrine, may be released by cutaneous nerves or resident and infiltrating
      cells within the skin. Systemic neuromediators and cutaneous nerves can influence
      a number of target cells within the skin, among them Langerhans cells. Most of
      the experimental evidence to date indicates a suppressive effect of the
      neurohormones and neuropeptides on Langerhans cell function and cutaneous
      inflammation, but it has become evident lately that the timing of exposure to a
      stimulus is critical to the outcome of the immune response. Thus, administration
      of a stress hormone or exposure to a stressor before the dendritic cell (DC)
      encounters an antigen (Ag) may diminish the immune response toward that Ag, while
      a stressor may enhance immune function when acting on a maturing DC or before
      reexposure to the Ag. The neuroendocrine regulation of skin DCs is a complex
      system allowing for a quick adaptation to various stressors. Such a system,
      originally evolved to defend the organism against invading pathogens and maintain
      homeostasis, may under certain conditions become unbalanced and ultimately
      exacerbate cutaneous inflammation.

PMID- 17192567
TI  - PPARgamma, a lipid-activated transcription factor as a regulator of dendritic
      cell function.
AB  - In recent years it became apparent that PPARgamma, besides being a key component
      of adipose tissue development and a target of insulin-sensitizing drugs, also has
      a role in immune cell differentiation and function. This receptor has been
      identified by us and others as a conductor of lipid handling in macrophages, and
      has roles also in inflammation control. Here we review recent advances on the
      role of this nuclear receptor in another key cell type of myeloid origin,
      dendritic cells (DCs). DCs are professional antigen-presenting cells having
      essential roles in antigen-uptake processing and presentation and in initiation
      of various forms of immune responses. It appears that PPARgamma is expressed and
      is active in myeloid DCs and likely to be a regulator of DC function by altering
      antigen uptake, maturation, activation, migration, cytokine production, and lipid
      antigen presentation. Thus PPARgamma is at the crossroads of lipid metabolism and
      innate immune response, and by studying its functions one has a unique
      opportunity to discern how these two seemingly distant fields (lipid metabolism
      and immune response) are interrelated. It is also possible that this receptor is
      a relevant target for pharmacological intervention in immune diseases such as
      chronic inflammation and autoimmune conditions.

PMID- 17192568
TI  - Roles of glia-derived cytokines on neuronal degeneration and regeneration.
AB  - Accumulation of activated microglia and reactive astrocytes is observed around
      degenerating neurons in various inflammatory or degenerative disorders in the
      central nervous system. These reactive glial cells may play either neurotoxic or
      neuroprotective roles. In this study, we examined the effects of glia-derived
      cytokines on neuronal degeneration and regeneration. Neuron-rich cultures were
      stimulated with supernatant of microglia and astrocytes stimulated with LPS, or a
      various concentrations of recombinant cytokines. Neurotoxicity was evaluated by
      an MTS assay. Neuronal damage was also evaluated by a frequency of dendritic
      beading, which was found to be an early feature of neuronal damage toward cell
      death. Effects of the cytokines on production of neurotrophic factors by
      astrocytes were also examined by RT-PCR for the expression of mRNA. Supernatant
      of LPS-stimulated microglia induced neuronal cell death. However, all the
      recombinant cytokines examined did not induce cell death, while IFNgamma and
      TNFalpha induced dendrite beading, an early feature of neuronal damage. IL-1beta
      and TNFalpha enhanced the production of neurotrophic factors by astrocytes. These
      observations suggest that glial cell-derived cytokines may synergistically
      function in neuronal degeneration with other toxic factors produced by activated
      microglia, and that some of them may also function in regeneration by inducing
      neurotrophic factors.

PMID- 17192569
TI  - Brain cytokines and the 5-HT system during poly I:C-induced fatigue.
AB  - Fatigue is evoked not only by peripheral factors, such as muscle fatigue, but
      also by the central nervous system (CNS). For example, it is generally known that
      the feeling of fatigue is greatly influenced by psychological aspects, such as
      motivation. However, little is known about the central mechanisms of fatigue. The
      clinical symptoms of chronic fatigue syndrome (CFS) are shown to include
      disorders in neuroendocrine, autonomic, and immune systems. On the other hand, it
      has been demonstrated that cytokines produced in the brain play significant roles
      in neural-immune interactions through their various central actions, including
      hypothalamo-pituitary and sympathetic activation, as well as immunosuppression.
      In this article, using the immunologically induced fatigue model, which was
      achieved by intraperitoneal (i.p.) injection of synthetic double-stranded RNAs,
      polyriboinosinic: polyribocytidylic acid (poly I:C) in rats, we show an
      involvement of brain interferon-alpha (IFN-alpha) and serotonin (5-HT)
      transporter (5-HTT) in the central mechanisms of fatigue. In the poly I:C-induced
      fatigue rats, expression of IFN-alpha and 5-HTT increased, while extracellular
      concentration of 5-HT in the medial prefrontal cortex decreased, probably on
      account of the enhanced expression of 5-HTT. Since the poly I:C-induced reduction
      of the running wheel activity was attenuated by a 5-HT(1A) receptor agonist, but
      not by 5-HT(2), 5-HT(3), or dopamine D(3) receptor agonists, it is suggested that
      the decrease in 5-HT actions on 5-HT(1A) receptors may at least partly contribute
      to the poly I:C-induced fatigue.

PMID- 17192570
TI  - Participation of the endocannabinoid system in the effect of TNF-alpha on
      hypothalamic release of gonadotropin-releasing hormone.
AB  - It is known that Delta(9)-tetrahydrocannabinol (THC), the major active ingredient
      of marijuana, can suppress reproductive function. Also, we reported previously
      that the endocannabinoid, anandamide (AEA), inhibited gonadotropin-releasing
      hormone (LHRH) release from medial basal hypothalamus (MBH) of male rats
      incubated in vitro as well as reduced plasma LH levels after i.c.v. AEA
      injections into the cerebral lateral ventricle. On the other hand, it is known
      that during endotoxemia the hypothalamic gonadotropin axis is inhibited.
      Therefore, the aim of the present study was to determine whether the effect of
      TNF-alpha, a proinflammatory cytokine induced by lipopolysaccharide (LPS) that
      inhibits LHRH release, is mediated by the activation of the endocannabinoid
      system. The intraperitoneal injection of LPS (5 mg/kg) as well as the i.c.v.
      injection of tumor necrosis factor-alpha (TNF-alpha) (100 ng/rat) increased
      significantly the AEA synthesis measured ex vivo in MBHs removed 3 h after the
      treatments. To examine the possibility that TNF-alpha also acted by increasing
      the synthesis of AEA that was released and activated the CB1-r followed by
      inhibition of LHRH release, we measured the effect of TNF-alpha on the AEA
      synthase activity in MBHs incubated in vitro. As expected, we found that TNF
      alpha (2.9 x 10(-9) M) increased the AEA synthesis. Second, we showed that TNF
      alpha reduced significantly the forskolin-stimulated LHRH release and that the
      CB1-r antagonist AM251 (10(-5) M) blocked that inhibition, supporting the
      hypothesis that TNF-alpha inhibits LHRH release, acting at least in part by
      activating the endocannabinoid system. Therefore, our data demonstrate a key role
      for the endocannabinoid system in the response of the reproductive system to
      inflammatory signals.

PMID- 17192571
TI  - Low-grade inflammation in chronic infectious diseases: paradigm of periodontal
      infections.
AB  - Increasing evidence implicates periodontitis, a chronic inflammatory disease of
      the tooth-supporting structures, as a potential risk factor for increased
      morbidity or mortality for several systemic conditions including cardiovascular
      disease (atherosclerosis, heart attack, and stroke), pregnancy complications
      (spontaneous preterm birth [SPB]), and diabetes mellitus. Cross-sectional, case
      control, and cohort studies indicate that periodontitis may confer two- and up to
      sevenfold increase in the risk for cardiovascular disease and premature birth,
      respectively. Given the recently acquired knowledge that systemic inflammation
      may contribute in the pathogenesis of atherosclerosis and may predispose to
      premature birth, research in the field of periodontics has focused on the
      potential of this chronic low-grade inflammatory condition to contribute to the
      generation of a systemic inflammatory phenotype. Consistent with this hypothesis
      clinical studies demonstrate that periodontitis patients have elevated markers of
      systemic inflammation, such as C-reactive protein (CRP), interleukin 6 (IL-6),
      haptoglobin, and fibrinogen. These are higher in periodontal patients with acute
      myocardial infarction (AMI) than in patients with AMI alone, supporting the
      notion that periodontal disease is an independent contributor to systemic
      inflammation. In the case of adverse pregnancy outcomes, studies on fetal cord
      blood from SBP babies indicate a strong in utero IgM antibody response specific
      to several oral periodontal pathogens, which induces an inflammatory response at
      the fetal-placental unit, leading to prematurity. The importance of periodontal
      infections to systemic health is further strengthened by pilot intervention
      trials indicating that periodontal therapy may improve surrogate cardiovascular
      outcomes, such as endothelial function, and may reduce four- to fivefold the
      incidence of premature birth. Nevertheless, further research is needed to fully
      discern the underlying mechanisms by which local chronic infections can have an
      impact on systemic health, and in this endeavor periodontal disease may serve as
      an ideal disease model.

PMID- 17192572
TI  - Local amplification of glucocorticoids by 11beta-hydroxysteroid dehydrogenase
      type 1 and its role in the inflammatory response.
AB  - Glucocorticoids are widely used to treat chronic inflammatory conditions
      including rheumatoid arthritis. They promote mechanisms important for normal
      resolution of inflammation, notably macrophage phagocytosis of leukocytes
      undergoing apoptosis. Prereceptor metabolism of glucocorticoids by 11beta
      hydroxysteroid dehydrogenase type 1 (11beta-HSD1) amplifies intracellular levels
      of glucocorticoids by oxoreduction of intrinsically inert cortisone (in humans,
      11-dehydrocorticosterone in mice) into active cortisol (corticosterone in mice)
      within cells expressing the enzyme. Recently, we have shown in a mouse model of
      acute inflammation, high expression of 11beta-HSD oxoreductase but not
      dehydrogenase activity in cells elicited rapidly in the peritoneum by a single
      thioglycollate injection. 11beta-HSD oxoreductase activity remained high in
      peritoneal cells until the inflammation resolved. In vitro, the 11beta-HSD1
      substrate, 11-dehydrocorticosterone, increased macrophage phagocytosis of
      apoptotic neutrophils to the same extent as corticosterone. This effect was
      dependent upon 11beta-HSD1: these cells solely expressed the type 1 11beta-HSD
      isozyme (not 11beta-HSD2), and carbenoxolone, an 11beta-HSD inhibitor, prevented
      the increase in phagocytosis elicited by 11-dehydrocorticosterone. Macrophages
      from 11beta-HSD1-deficient mice failed to respond to 11-dehydrocorticosterone. In
      vivo, 11beta-HSD1-deficient mice showed a delay in acquisition of macrophage
      phagocytic competence and had an increased number of free apoptotic neutrophils
      during sterile peritonitis. Importantly, in preliminary experiments, 11beta-HSD1
      deficient mice exhibited delayed resolution of inflammation in experimental
      arthritis. These findings suggest 11beta-HSD1 may be a component of mechanisms
      engaged early during the inflammatory response that promote its subsequent
      resolution.

PMID- 17192573
TI  - Immunoneuroendocrine interactions in Chagas disease.
AB  - We investigated immunoneuroendocrine interactions in vivo and in vitro following
      infection by Trypanosoma cruzi, the causative agent of Chagas disease. In a first
      set of experiments, we studied the hypothalamus-pituitary-adrenal axis. Nests of
      parasites were seen in the adrenal gland, whereas T. cruzi-specific PCR gene
      amplification product was found in both the adrenal and pituitary glands of
      infected mice. These endocrine glands also revealed alterations including
      vascular stasis, increase in the deposition of extracellular matrix (ECM), as
      well as T cell and macrophage infiltration. Functionally, we found a decrease in
      corticotrophin-releasing hormone and an increase in corticosterone contents, in
      hypothalamus and serum, respectively, whereas no significant changes were seen in
      serum adrenocortricotropic hormone of infected animals. Nevertheless, the serum
      levels of interleukin-6 (known to directly stimulate glucocorticoid secretion)
      were increased, as compared to controls. Considering the presence of T cells
      within the nervous tissue of chagasic animals, we performed a number of in vitro
      experiments co-culturing spleen-derived T cells from control or infected mice,
      with neuronal cells (being or not being directly infected in vitro). In
      particular, we looked for ECM-mediated interactions, known to affect T cell
      migration. We found an increase in ECM deposition in infected cultures, as
      compared to controls. Moreover, adhesion of T cells was enhanced when neuronal
      cells were infected in vitro, or when T cells were derived from T. cruzi-infected
      mice, events that could be abrogated with anti-ECM antibodies. Together, the data
      summarized above clearly reveal that neuroendocrine axes are altered in
      experimental Chagas disease.

PMID- 17192574
TI  - Thymus-dependent T cell tolerance of neuroendocrine functions: principles,
      reflections, and implications for tolerogenic/negative self-vaccination.
AB  - Under the evolutionary pressure exerted by the emergence of adaptive immunity and
      its inherent risk of horror autotoxicus, the thymus appeared some 500 million
      years ago as a novel lymphoid structure able to prevent autoimmunity and to
      orchestrate self-tolerance as a cornerstone in the physiology of the immune
      system. Also, the thymus plays a prominent role in T cell education to
      neuroendocrine principles. Some self-antigens (oxytocin, neurotensin, insulin
      like growth factor 2 [IGF-2]) have been selected to be predominantly expressed in
      thymic epithelium and to be presented to thymus T cells for educating them to
      tolerate other antigens related to them. In the insulin family, IGF2 is
      dominantly transcribed in cortical (c) and medullary (m) thymic epithelial cells
      (TECs), whereas the insulin gene (INS) is expressed at low level by only a few
      subsets of mTECs. Intrathymic transcription of both IGF2 and INS is under the
      control of the autoimmune regulator (Aire) gene. The highest concentrations of
      IGF-2 in the thymus explain why this peptide is much more tolerated than insulin,
      and why tolerance to IGF-2 is so difficult to break by active immunization. The
      high level of tolerance to IGF-2 is correlated to the development of a
      tolerogenic/regulatory profile when the sequence B11-25 of IGF-2 (homologous to
      the autoantigen insulin B9-23) is presented to DQ8+ type 1 diabetic patients.
      Since subcutaneous and oral insulin does not exert any tolerogenic properties,
      IGF-2 and other thymus self-antigens related to type 1 diabetes (T1D) should be
      preferred to insulin for the design of novel specific antigen-based preventive
      approaches against T1D.

PMID- 17192575
TI  - Molecular understanding of cytokine-steroid hormone dialogue: implications for
      human diseases.
AB  - Highly sophisticated mechanisms confer upon the immune system the capacity to
      respond with a certain degree of autonomy. However, the final outcome of an
      adaptative immune response depends on the interaction with other systems of the
      organism. The immune-neuroendocrine systems have an intimate cross-communication,
      making possible a satisfactory response to environmental changes. Part of this
      interaction occurs through cytokines and steroid hormones. The last step of this
      crosstalk is at the molecular level. In this article we will focus on the
      physical and functional interrelationship between cytokine signaling pathway
      activated transcription factors (TFs) and steroid receptors in different cell
      models, where the signals triggered by cytokines and steroid hormones have major
      roles: (1) the ligand-dependent-activated glucocorticoid receptor (GR) influence
      the genetic program that specifies lineage commitment in T helper (Th) cell
      differentiation. How posttranslational modifications of several TFs as well as
      nuclear hormone receptors could be implicated in the molecular crosstalk between
      the immune-neuroendocrine messengers is discussed. (2) glucocorticoid (GC)
      antagonism on the TCR-induced T cell apoptosis. (3) estrogen receptor/TGF-beta
      family proteins molecular interaction implicated on pituitary prolactinomas
      pathogenesis. The functional crosstalk at the molecular level between immune and
      steroids signals is essential to determine an integrative response to both
      mediators (which in the last instance results in a new gene activation/repression
      profile) and constitutes the ultimate integrative level of interaction between
      the immune and neuroendocrine systems.

PMID- 17192576
TI  - The role of toll-like receptors in the immune-adrenal crosstalk.
AB  - Sepsis and septic shock remain major health concerns worldwide, and rapid
      activation of adrenal steroid release is a key event in the organism's first line
      of defense during this form of severe illness. Toll-like receptors (TLRs) are
      critical in the early immune response upon bacterial infection, and recent data
      from our lab demonstrate a novel link between the innate immune system and the
      adrenal stress response mediated by TLRs. Glucocorticoids and TLRs regulate each
      other in a bidirectional way. Bacterial toxins acting through TLRs directly
      activate adrenocortical steroid release. TLR-2 and TLR-4 are expressed in human
      and mice adrenals and TLR-2 deficiency is associated with an impaired
      glucocorticoid response. Furthermore, TLR-2 deficiency in mice is associated with
      marked cellular alterations in adrenocortical tissue. TLR-2-deficient mice have
      an impaired adrenal corticosterone release following inflammatory stress induced
      by bacterial cell wall compounds. This defect appears to be associated with a
      decrease in systemic and intraadrenal cytokine expression. In conclusion, TLRs
      play a crucial role in the immune-adrenal crosstalk. This close functional
      relationship needs to be considered in the treatment of inflammatory diseases
      requiring an intact adrenal stress response.

PMID- 17192577
TI  - Adrenocortical tumorigenesis.
AB  - Through the widespread use of imaging techniques with great sensitivity adrenal
      tumors are often diagnosed as an incidental finding. Although the majority of
      these adrenal lesions are benign and without evidence of endocrine activity or
      malignancy, hormone hypersecretion needs to be ruled out by specific tests. In
      addition to the classical forms of overt adrenocortical hypersecretion, it has
      become evident over the recent years that modest adrenocortical steroid autonomy
      as present in normokalemic primary aldosteronism and subclinical Cushing's
      syndrome is also associated with a significant morbidity. However, detection and
      differential diagnosis of these subtle changes in adrenal steroidogenesis can
      pose a diagnostic challenge to the clinician and is dependent on tests with
      reliable sensitivity and specificity. Regulation of adrenocortical development
      and growth, which results in clinical symptoms if disrupted, is dependent upon
      the distinct spatiotemporal expression of a variety of transcription factors as
      well as stimulation by extra-adrenal peptide hormones. Contributions to the
      elucidation of growth regulation of the adrenal cortex come from rare familiar
      syndromes associated with adrenocortical tumors, expression studies of adrenal
      tumor samples, in vitro studies on adrenocortical tumor cell lines, and mouse
      models displaying adrenal growth defects. In this review, we will summarize the
      important molecular aspects of adrenal tumorigenesis and highlight some prospects
      for clinical applications.

PMID- 17192578
TI  - Alpha 2-adrenergic receptors decrease DNA replication and cell proliferation and
      induce neurite outgrowth in transfected rat pheochromocytoma cells.
AB  - Alpha 2-adrenergic receptors (alpha(2)-ARs) have a widespread distribution in the
      central nervous system (CNS) and affect a number of biochemical and behavioral
      functions, including stimulation of prefrontal cortex (PFC) and cognitive
      function. In addition to its role as a classical neurotransmitter, norepinephrine
      (NE) has been recently shown to exert an important influence on the plasticity in
      areas of the brain where neurogenesis persists in the adult, notably the
      subgranular zone (SGZ) within the dentate gyrus of the hippocampus and the
      olfactory bulb (OB). In regulating adult neurogenesis, the noradrenergic system
      is functionally integrated with chronic stress and depression. Chronic stress,
      depression, or depletion of NE in vivo suppress, and antidepressant treatments
      induce hippocampal neurogenesis by down- or upregulating, respectively, cell
      proliferation. In the present study we show that alpha(2)-AR subtypes promote the
      differentiation rather than cell proliferation of PC12 cells. It is conceivable
      that alpha(2)-ARs might contribute neurotrophic actions in vivo synergistically
      or in permutation with other neurotrophic factors.

PMID- 17192579
TI  - Pheochromocytoma: physiopathologic implications and diagnostic evaluation.
AB  - Pheochromocytoma (PHEO) is a chromaffin cell tumor embryologically arising from
      the neural crest tissue. The dominant secretory products of PHEO are
      catecholamines: noradrenaline (norepinephrine), adrenaline (epinephrine), and to
      a lesser extent dopamine. In addition to catecholamines, PHEO cells also
      elaborate and release several neuropeptides and inflammatory cytokines which can
      exert intra-adrenal and extra-adrenal systemic effects and cause characteristic
      clinical syndromes. In a concise review we present the intra-adrenal and extra
      adrenal pathophysiologic implications of PHEO and the nuclear medicine modalities
      that permit functional imaging of physiological processes and help localize these
      tumors. The specific pathways of synthesis, metabolism, and inactivation of
      catecholamines (of PHEOs and paragangliomas) can be used as means to develop
      suitable tracers for positron emission tomography (PET) ligands. In this review
      we focus on imaging with PET using [(18)F]-fluorodopamine, [(18)F]
      fluorohydroxyphenylalanine, [(11)C]-epinephrine, or [(11)C]-hydroxyephedrine and
      examine how functional imaging can often complement traditional anatomical
      imaging modalities and other scintigraphic techniques.

PMID- 17192580
TI  - Beyond heart rate variability: vagal regulation of allostatic systems.
AB  - The autonomic nervous system (ANS) plays a role in a wide range of somatic and
      mental diseases. Whereas the role of the ANS in the regulation of the
      cardiovascular system seems evident, its role in the regulation of other systems
      associated with allostasis is less clear. Using a model of neurovisceral
      integration we describe how the ANS and parasympathetic tone in particular may be
      associated with the regulation of allostatic systems associated with glucose
      regulation, hypothalamic-pituitary-adrenal (HPA) axis function, and inflammatory
      processes. Decreased vagal function and heart rate variability (HRV) were shown
      to be associated with increased fasting glucose and hemoglobin A1c levels,
      increased overnight urinary cortisol, and increased proinflammatory cytokines and
      acute-phase proteins. All of these factors have been associated with increased
      allostatic load and poor health. Thus, vagal activity appears to play an
      inhibitory function in the regulation of allostatic systems. The prefrontal
      cortex and the amygdala are important central nervous system structures linked to
      the regulation of these allostatic systems via the vagus nerve. Finally, the
      identification of this neurovisceral regulatory system may help to illuminate the
      pathway via which psychosocial factors may influence health and disease.

PMID- 17192581
TI  - Interleukin-6: a cytokine and/or a major modulator of the response to somatic
      stress.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis and the proinflammatory cytokines
      (and interleukin-6 [IL-6] in particular) are enmeshed in the response to somatic
      stress, either in health or in acute or chronic disease. Usually IL-6 is elevated
      in states of septic (such as sepsis) or aseptic inflammation (such as rheumatoid
      arthritis). Exercise is a form of somatic stress. Local tissue IL-6 elevation is
      noted during shorter and less intense exercise, whereas brief peripheral IL-6
      "bursts" are observed with longer and more intense exercise. Therapeutic
      interventions that target IL-6 or its soluble receptor are currently assessed,
      with an emphasis on autoimmune diseases and inflammatory conditions.

PMID- 17192582
TI  - The role of stress in the clinical expression of thyroid autoimmunity.
AB  - During stress, activation of the hypothalamic-pituitary-adrenal axis and the
      sympathoadrenal system leads to increased secretion of glucocorticoids and
      catecholamines, respectively, in order to maintain homeostasis. Recent evidence
      suggests that stress hormones, acting on antigen-presenting immune cells, may
      influence the differentiation of bipotential T helper (Th) cells away from Th1
      and toward a Th2 phenotype. This results in suppression of cellular immunity and
      potentiation of humoral immunity. Thyroid autoimmunity is clinically expressed as
      Hashimoto's thyroiditis (HT) and its variants (sporadic or postpartum
      thyroiditis) or as Grave's disease (GD). The different phenotypic expression of
      thyroid autoimmunity is largely dependent on the balance of Th1 versus Th2 immune
      response. A predominantly Th1-mediated immune activity may promote apoptotic
      pathways on thyroid follicular cells leading to thyroid cell destruction and HT.
      Conversely, predominance of Th2-mediated immune response may induce antigen
      specific B lymphocytes to produce anti-TSH receptor (TSHr) antibodies causing GD.
      The weight of evidence from epidemiological and case-control studies supports an
      association between stress and GD. On the other hand, there is little information
      available on the effect of stress on HT, but there is evidence for an increase in
      postpartum thyroiditis, following the cellular immune suppressive effect of
      pregnancy. Whether stress has a causative effect on GD remains elusive.
      Circumstantial evidence supports the hypothesis that stress may influence the
      clinical expression of thyroid autoimmunity in susceptible individuals favoring
      the development of GD by shifting the Th1-Th2 balance away for Th1 and toward
      Th2. Conversely, recovery from stress or the immune suppressive effect of
      pregnancy may induce a Th2 to Th1 "return shift" leading to autoimmune (sporadic)
      or postpartum thyroiditis, respectively.

PMID- 17192583
TI  - Annexin 1, glucocorticoids, and the neuroendocrine-immune interface.
AB  - Annexin 1 (ANXA1) was originally identified as a mediator of the anti
      inflammatory actions of glucocorticoids (GCs) in the host defense system.
      Subsequent work confirmed and extended these findings and also showed that the
      protein fulfills a wider brief and serves as a signaling intermediate in a number
      of systems. ANXA1 thus contributes to the regulation of processes as diverse as
      cell migration, cell growth and differentiation, apoptosis, vesicle fusion, lipid
      metabolism, and cytokine expression. Here we consider the role of ANXA1 in the
      neuroendocrine system, particularly the hypothalamo-pituitary-adrenocortical
      (HPA) axis. Evidence is presented that ANXA1 plays a critical role in effecting
      the negative feedback effects of GCs on the release of corticotrophin (ACTH) and
      its hypothalamic-releasing hormones and that it is particularly pertinent to the
      early-onset actions of the steroids that are mediated via a nongenomic mechanism.
      The paracrine/juxtacrine mode of ANXA1 action is discussed in detail, with
      particular reference to the significance of the secondary processing of ANXA1,
      the processes that control the intracellular and transmembrane trafficking of the
      protein of the molecule and the mechanism of ANXA1 action on its target cells. In
      addition, the role of ANXA1 in the perinatal programming of the HPA axis is
      discussed.

PMID- 17192585
TI  - The age of reverse biochemistry.

PMID- 17192586
TI  - Analysis and prediction of functionally important sites in proteins.
AB  - The rapidly increasing volume of sequence and structure information available for
      proteins poses the daunting task of determining their functional importance.
      Computational methods can prove to be very useful in understanding and
      characterizing the biochemical and evolutionary information contained in this
      wealth of data, particularly at functionally important sites. Therefore, we
      perform a detailed survey of compositional and evolutionary constraints at the
      molecular and biological function level for a large set of known functionally
      important sites extracted from a wide range of protein families. We compare the
      degree of conservation across different functional categories and provide
      detailed statistical insight to decipher the varying evolutionary constraints at
      functionally important sites. The compositional and evolutionary information at
      functionally important sites has been compiled into a library of functional
      templates. We developed a module that predicts functionally important columns
      (FIC) of an alignment based on the detection of a significant "template match
      score" to a library template. Our template match score measures an alignment
      column's similarity to a library template and combines a term explicitly
      representing a column's residue composition with various evolutionary
      conservation scores (information content and position-specific scoring matrix
      derived statistics). Our benchmarking studies show good sensitivity/specificity
      for the prediction of functional sites and high accuracy in attributing correct
      molecular function type to the predicted sites. This prediction method is based
      on information derived from homologous sequences and no structural information is
      required. Therefore, this method could be extremely useful for large-scale
      functional annotation.

PMID- 17192588
TI  - Contributions of the interdomain loop, amino terminus, and subunit interface to
      the ligand-facilitated dimerization of neurophysin: crystal structures and
      mutation studies of bovine neurophysin-I.
AB  - Current evidence indicates that the ligand-facilitated dimerization of
      neurophysin is mediated in part by dimerization-induced changes at the hormone
      binding site of the unliganded state that increase ligand affinity. To elucidate
      other contributory factors, we investigated the potential role of neurophysin's
      short interdomain loop (residues 55-59), particularly the effects of loop residue
      mutation and of deleting amino-terminal residues 1-6, which interact with the
      loop and adjacent residues 53-54. The neurophysin studied was bovine neurophysin
      I, necessitating determination of the crystal structures of des 1-6 bovine
      neurophysin-I in unliganded and liganded dimeric states, as well as the structure
      of its liganded Q58V mutant, in which peptide was bound with unexpectedly
      increased affinity. Increases in dimerization constant associated with selected
      loop residue mutations and with deletion of residues 1-6, together with
      structural data, provided evidence that dimerization of unliganded neurophysin-I
      is constrained by hydrogen bonding of the side chains of Gln58, Ser56, and Gln55
      and by amino terminus interactions, loss or alteration of these hydrogen bonds,
      and probable loss of amino terminus interactions, contributing to the increased
      dimerization of the liganded state. An additional intersubunit hydrogen bond from
      residue 81, present only in the liganded state, was demonstrated as the largest
      single effect of ligand binding directly on the subunit interface. Comparison of
      bovine neurophysins I and II indicates broadly similar mechanisms for both, with
      the exception in neurophysin II of the absence of Gln55 side chain hydrogen bonds
      in the unliganded state and a more firmly established loss of amino terminus
      interactions in the liganded state. Evidence is presented that loop status
      modulates dimerization via long-range effects on neurophysin conformation
      involving neighboring Phe22 as a key intermediary.

PMID- 17192587
TI  - Studying multisite binary and ternary protein interactions by global analysis of
      isothermal titration calorimetry data in SEDPHAT: application to adaptor protein
      complexes in cell signaling.
AB  - Multisite interactions and the formation of ternary or higher-order protein
      complexes are ubiquitous features of protein interactions. Cooperativity between
      different ligands is a hallmark for information transfer, and is frequently
      critical for the biological function. We describe a new computational platform
      for the global analysis of isothermal titration calorimetry (ITC) data for the
      study of binary and ternary multisite interactions, implemented as part of the
      public domain multimethod analysis software SEDPHAT. The global analysis of
      titrations performed in different orientations was explored, and the potential
      for unraveling cooperativity parameters in multisite interactions was assessed in
      theory and experiment. To demonstrate the practical potential and limitations of
      global analyses of ITC titrations for the study of cooperative multiprotein
      interactions, we have examined the interactions of three proteins that are
      critical for signal transduction after T-cell activation, LAT, Grb2, and Sos1. We
      have shown previously that multivalent interactions between these three molecules
      promote the assembly of large multiprotein complexes important for T-cell
      receptor activation. By global analysis of the heats of binding observed in sets
      of ITC injections in different orientations, which allowed us to follow the
      formation of binary and ternary complexes, we observed negative and positive
      cooperativity that may be important to control the pathway of assembly and
      disassembly of adaptor protein particles.

PMID- 17192589
TI  - A complete algorithm to resolve ambiguity for intersubunit NOE assignment in
      structure determination of symmetric homo-oligomers.
AB  - Assignment of nuclear Overhauser effect (NOE) data is a key bottleneck in
      structure determination by NMR. NOE assignment resolves the ambiguity as to which
      pair of protons generated the observed NOE peaks, and thus should be restrained
      in structure determination. In the case of intersubunit NOEs in symmetric homo
      oligomers, the ambiguity includes both the identities of the protons within a
      subunit, and the identities of the subunits to which they belong. This paper
      develops an algorithm for simultaneous intersubunit NOE assignment and C(n)
      symmetric homo-oligomeric structure determinations, given the subunit structure.
      By using a configuration space framework, our algorithm guarantees completeness,
      in that it identifies structures representing, to within a user-defined
      similarity level, every structure consistent with the available data (ambiguous
      or not). However, while our approach is complete in considering all conformations
      and assignments, it avoids explicit enumeration of the exponential number of
      combinations of possible assignments. Our algorithm can draw two types of
      conclusions not possible under previous methods: (1) that different assignments
      for an NOE would lead to different structural classes, or (2) that it is not
      necessary to uniquely assign an NOE, since it would have little impact on
      structural precision. We demonstrate on two test proteins that our method reduces
      the average number of possible assignments per NOE by a factor of 2.6 for MinE
      and 4.2 for CCMP. It results in high structural precision, reducing the average
      variance in atomic positions by factors of 1.5 and 3.6, respectively.

PMID- 17192590
TI  - Human lysosomal DNase IIalpha contains two requisite PLD-signature (HxK) motifs:
      evidence for a pseudodimeric structure of the active enzyme species.
AB  - Lysosomal DNase IIalpha is essential for DNA waste removal and auxiliary
      apoptotic DNA fragmentation in higher eukaryotes. Despite the key role of this
      enzyme, little is known about its structure-function relationships. Here,
      mutational and biochemical analyses were used to characterize human DNase IIalpha
      variants expressed in mammalian cells. The resulting data strongly support the
      hypothesis that the enzyme is a monomeric phospholipase D-family member with a
      pseudodimeric protein fold. According to our results, DNase IIalpha contains two
      requisite PLD-signature motifs ((113)HTK(115) and (295)HSK(297)) in the N- and C
      terminal subdomains, respectively, that together form a single active site. Based
      on these data, we present an experimentally validated structural model of DNase
      IIalpha.

PMID- 17192591
TI  - Atomic-resolution crystal structure of thioredoxin from the acidophilic bacterium
      Acetobacter aceti.
AB  - The crystal structure of thioredoxin (AaTrx) from the acetic acid bacterium
      Acetobacter aceti was determined at 1 A resolution. This is currently the highest
      resolution crystal structure available for any thioredoxin. Thioredoxins
      facilitate thiol-disulfide exchange, a process that is expected to be slow at the
      low pH values encountered in the A. aceti cytoplasm. Despite the apparent need to
      function at low pH, neither the active site nor the surface charge distribution
      of AaTrx is notably different from that of Escherichia coli thioredoxin.
      Apparently the ancestral thioredoxin was sufficiently stable for use in A. aceti
      or the need to interact with multiple targets constrained the variation of
      surface residues. The AaTrx structure presented here provides a clear view of all
      ionizable protein moieties and waters, a first step in understanding how thiol
      disulfide exchange might occur in a low pH cytoplasm, and is a basis for
      biophysical studies of the mechanism of acid-mediated unfolding. The high
      resolution of this structure should be useful for computational studies of
      thioredoxin function, protein structure and dynamics, and side-chain ionization.

PMID- 17192592
TI  - A phosphate-binding subsite in bovine pancreatic ribonuclease A can be converted
      into a very efficient catalytic site.
AB  - A general acid-base catalytic mechanism is responsible for the cleavage of the
      phosphodiester bonds of the RNA by ribonuclease A (RNase A). The main active site
      is formed by the amino acid residues His12, His119, and Lys41, and the process
      follows an endonucleolytic pattern that depends on the existence of a
      noncatalytic phosphate-binding subsite adjacent, on the 3'-side, to the active
      site; in this region the phosphate group of the substrate establishes
      electrostatic interactions through the side chains of Lys7 and Arg10. We have
      obtained, by means of site-directed mutagenesis, RNase A variants with His
      residues both at positions 7 and 10. These mutations have been introduced with
      the aim of transforming a noncatalytic binding subsite into a putative new
      catalytic active site. The RNase activity of these variants was determined by the
      zymogram technique and steady-state kinetic parameters were obtained by
      spectrophotometric methods. The variants showed a catalytic efficiency in the
      same order of magnitude as the wild-type enzyme. However, we have demonstrated in
      these variants important effects on the substrate's cleavage pattern. The
      quadruple mutant K7H/R10H/H12K/H119Q shows a clear increase of the exonucleolytic
      activity; in this case the original native active site has been suppressed, and,
      as consequence, its activity can only be associated to the new active site. In
      addition, the mutant K7H/R10H, with two putative active sites, also shows an
      increase in the exonucleolytic preference with respect to the wild type, a fact
      that may be correlated with the contribution of the new active site.

PMID- 17192594
TI  - 10th Summit Meeting consensus: recommendations for regulatory approval for
      hormonal male contraception.

PMID- 17192595
TI  - Effects of seminal plasma on cooling-induced capacitative changes in boar sperm.
AB  - Porcine seminal plasma (SP) has been shown to contain factors that have a
      decapacitative or capacitation-inhibiting effect on sperm. The objectives of the
      present study were to compare the capacitative changes observed in cooled sperm
      with those seen in sperm after in vitro capacitation and to determine whether SP
      could prevent these changes. Sperm were subjected to incubation or to slow
      cooling under noncapacitating or capacitating conditions. The effect of SP on
      protein tyrosine phosphorylation and the ability of the sperm to undergo an
      acrosome reaction (AR) were determined. Cooled sperm displayed an increased level
      of tyrosine phosphorylation and a higher percentage of induced AR sperm compared
      to incubated sperm. The addition of SP inhibited the number of ARs that occurred
      during incubation and cooling. These results suggest that cooling of sperm
      augments the capacitative changes in sperm, and that SP contains a factor(s) that
      effectively prevents these changes.

PMID- 17192596
TI  - Impaired semen quality associated with environmental DDT exposure in young men
      living in a malaria area in the Limpopo Province, South Africa.
AB  - The pesticide DDT [1,1,1-trichloro-2,2-bis(chlorodiphenyl)ethane] is 1 of the 12
      persistent organic pollutants (POPs) under negotiation at the Stockholm
      Convention to restrict or ban their production and use because of their toxicity,
      resistance to breakdown, bioaccumulation, and potential for being transported
      over long distances. DDT has estrogenic potential, and the main metabolite, p,p'
      dichlorodiphenyl-dichloroethylene (p,p'-DDE), is a potent antiandrogen. In
      response to mounting evidence on the endocrine-disrupting influence of
      environmental chemicals on human health, this epidemiological study was initiated
      to test the hypothesis that nonoccupational exposure to DDT affects male
      reproductive parameters. In a cross-sectional study, healthy male subjects
      (n=311) between 18 and 40 years (23+/-5) of age were recruited from 3 communities
      in an endemic malaria area in which DDT is sprayed annually. A semen analysis
      according to World Health Organization (WHO) standards was performed. The
      Hamilton Thorne Computer Assisted Sperm Analysis (CASA) system was simultaneously
      used to determine additional sperm motility parameters. Blood plasma samples were
      assayed for p,p'-DDT and metabolites as a measure of exposure. The exposure
      levels were expressed as lipid-adjusted p,p'-DDT and p,p'-DDE values. The mean
      p,p'-DDT and p,p'-DDE concentrations were 90.23 microg/g(+/-102.4) and 215.47
      microg/g(+/-210.6), respectively. The multivariate linear regression analyses
      indicated that mean CASA motility was lower with a higher p,p'-DDE concentration
      (beta=-0.02, P=.001) and the CASA parameter beat cross-frequency (BCF) was higher
      with a higher p,p'-DDT concentration (beta=0.01, P=.000). There was also a
      statistically significant positive association between percent sperm with
      cytoplasmic droplets and p,p'-DDT concentration (beta=0.0014, P=.014). The
      ejaculate volume (mean 1.9+/-1.33 mL) was lower than the normal range (>or=2.0
      mL) according to WHO, and a significant decrease with increasing p,p'-DDE values
      was seen for both square root-transformed volume (beta=-0.0003; P=.024) and count
      (beta=-0.003; P=.04). Although there were no associations between either p,p'-DDT
      or p,p'-DDE concentrations and the rest of the seminal parameters, the incidence
      of teratozoospermia (99%; normal sperm<15%) was high. Twenty-eight percent of the
      study group presented with oligozoospermia (<20x10(6) sperm/mL), which had a
      significant positive association with p,p'-DDE (odds ratio [OR]=1.001, P=.03).
      There was a significant positive association between participants with
      asthenozoospermia (32%) and p,p'-DDT (OR 1.003, P=.006) and p,p'-DDE (OR 1.001,
      P=.02). The results imply that nonoccupational exposure to DDT is associated with
      impaired seminal parameters in men. The high exposure levels of p,p'-DDT and p,p'
      DDE are of concern because these levels could have far-reaching implications for
      reproductive and general health.

PMID- 17192597
TI  - Regional variations in semen quality of community-dwelling young men from
      Flanders are not paralleled by hormonal indices of testicular function.
AB  - Epidemiological studies of sperm quality are hampered by problems such as low
      participation rates and poor comparability of results due to methodological
      differences in semen analysis. More objective sperm quality-related serum markers
      would facilitate worldwide comparisons of male reproductive status. Our
      objectives were to investigate to what extent a set of hormonal indices of
      testicular function, previously established in a clinical setting, could predict
      regional variations in seminal parameters in men from the general population. We
      recruited 101 men aged 20-40 years from two regions in Flanders, and assessed
      their sperm parameters and levels of serum reproductive hormones. In one region
      compared to another, the participants had lower sperm counts (by 34%; P=.06),
      lower total sperm counts (by 41%; P=.02) and poorer sperm morphology (by 32%;
      P<.001), which were paralleled by significantly lower levels of free testosterone
      (by 11%; P=.03), while for total testosterone (T) and follicle-stimulating
      hormone (FSH), the differences were not significant (both P=.09) at 10% and 17%,
      respectively. There were no differences in inhibin B and the T to luteinizing
      hormone (LH) ratio, which are markers of testicular function. Receiver operating
      characteristic curve analysis revealed that T:LH, inhibin B, and the inhibin
      B/FSH ratio had significant discriminatory power between men with sperm
      concentrations below or above 13.5x10(6)/mL. Regional variations in the semen
      quality of community-dwelling individuals are not necessarily reflected in
      altered hormonal indices of testicular function and thus, these markers,
      validated in clinical settings, are not valid substitutes for the traditional
      semen quality assessment used in epidemiological population studies.

PMID- 17192599
TI  - Gonosomal mosaicism from deleted Y chromosomal nondisjunction.

PMID- 17192598
TI  - Acrosome reaction induced by recombinant human zona pellucida 3 peptides
      rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348 and their mechanism.
AB  - To explore the biological characteristics of the recombinant zona pellucida 3
      (ZP3) peptides of rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348,
      we examined whether rhuZP3a22 approximately 176 or rhuZP3b177 approximately 348
      trigger the acrosome reaction (AR) of human spermatozoa and we investigated the
      underlying mechanism. The assessment of AR was performed using chlortetracycline
      staining. The intracellular free calcium concentration ([Ca2+]i) in Fura-2/AM
      loaded human sperm was monitored with a spectrofluorophotometer. We found that
      rhuZP3a22 approximately 176 and rhuZP3b177 approximately 348 were capable of
      eliciting AR at different concentrations. With the addition of either peptide,
      the [Ca2+]i level was raised to a peak with or without a plateau. The AR could be
      inhibited by pertussis toxin (PTX), EGTA, and pimozide (a T-type calcium channel
      blocker), whereas verapamil was less effective in this regard. The results of the
      present study suggest that peptides rhuZP3a22 approximately 176 and rhuZP3b177
      approximately 348 have a role similar to human ZP3, and that the mechanism of the
      response to the peptides involves influx of calcium, the G protein pathway, and a
      T-type calcium channel.

PMID- 17192600
TI  - Cytoskeleton vimentin disruption of mouse sertoli cells injured by nitrogen
      mustard in vitro.
AB  - Reproductive toxicity is one of the potential side effects of anticancer
      alkylating agents, with potential effects on vimentin intermediate filaments, one
      of the main components of the Sertoli cytoskeleton. Research suggests (Aumuller
      et al, 1988; Aumuller et al, 1992) that the highly organized and active Sertoli
      cytoskeleton is important in spermatogenesis. The aim of the current study was to
      investigate the effects of alkylating agents on vimentin filament expression in
      vitro. Sertoli cells, isolated from 20-day-old mice testes, were cultured for 5
      days and then incubated with 0, 50, 100, and 200 micromol/L nitrogen mustard
      (HN2). Morphologic changes in Sertoli cells were observed per 30-minute interval
      at 12-hour exposure time points to 100 micromol/L HN2. Vimentin expression was
      investigated by immunocytochemistry at 6 hours and 24 hours posttreatment and
      reverse transcriptase polymerase chain reaction and Western blot at 12 hours
      posttreatment with 50, 100, and 200 micromol/L HN2. Exposure to HN2 resulted in a
      comparatively small Sertoli cell body with diminished cytoplasm. Sertoli cells
      were shrunk or detached. Cytoskeletal disruption increased with increasing HN2
      concentration. The optical density values of vimentin antibody and expression of
      vimentin mRNA and protein were significantly decreased with increasing
      concentration of HN2. Significant treatment dose-dependent and time-dependent
      differences of vimentin mRNA and protein expression levels were also noted. Our
      data suggest that the change in the biochemical properties of vimentin may
      indicate that one of the mechanisms of reproductive toxicity resulting from HN2
      is disruption of Sertoli cell vimentin filament structure, accompanied by a down
      regulation of vimentin expression.

PMID- 17192602
TI  - Photo-induced covalent attachment of agonists as a tool to study allosteric
      mechanisms of nicotinic acetylcholine receptors.
AB  - Muscular and neuronal nicotinic acetylcholine receptors (nAChRs) are pentameric
      ligand-gated ion channels and contain either two or five binding sites for
      acetylcholine (ACh). Binding of ACh molecules on the nAChR will trigger the fast
      opening of the channel and subsequent slow desensitization process. Neuronal
      alpha7 nicotinic receptors are made up of five identical subunits and possess
      five binding sites for ACh; this raises the question of how many sites must be
      occupied before channel opening. However, the effect of each ligand binding on
      gating is difficult to assess because of the reversible aspect of ligand binding
      at each site. One solution is to photochemically tether agonists to their binding
      sites. Such methodology has been applied elegantly and successfully on the
      homotetrameric cyclic-nucleotide-gated channels to evaluate the functional
      effects of each ligand binding on gating (Ruiz and Karpen, 1997). We therefore
      decided to develop a similar approach on Torpedo and neuronal alpha7 nAChRs with
      the photoactivatable agonist AC5 to investigate the effect of binding site
      occupancy on allosteric transitions of the receptor. In the dark, AC5 (see
      structure below) evokes robust currents on oocytes expressing Torpedo nAChR,
      displaying maximal amplitude comparable to ACh, with EC50 = 1.2 microM (Mourot et
      al., 2005). When the voltage-clamp oocyte was exposed to UV light in the presence
      of 30 microM AC5 for 50 s, there was a prolonged activation of the Torpedo nAChR,
      not reversible by washing, but inhibited by the noncompetitive blockers
      tetracaine and proadifen (see structure below). Both UV light and AC5 are
      required for this effect. However, further studies are required to determine
      whether the gradual decrease of the inward current reflects a slow
      desensitization process. AC5 is thus a potent photoactivatable agonist of the
      nAChR, which is able, upon UV irradiation, to incorporate covalently into the ACh
      binding sites and to prolong activation of the nAChR. By extending this
      methodology to patch-clamp experiments, we will be able to incorporate one or
      several AC5s covalently into the muscular and neuronal nAChR at the single
      channel level. Such study will help us understand the observed cooperative effect
      of gating and will contribute decisively to the controversial concerted vs
      sequential models for nAChR allosteric transitions.

PMID- 17192603
TI  - Nicotinic acetylcholine receptor properties are modulated by surrounding lipids:
      an in vivo study.
AB  - In vitro studies carried out on liposomes of defined composition showed that
      nicotinic acetylcholine receptors (nAChRs) are fully functional when they are
      reconstituted in a heterogeneous lipid matrix, such as that provided by crude
      soybean (asolectin [R-Aso]) lipids. However, when they are reconstituted in plain
      phosphatidylcholine (R-PC) lipids, their functional activity is completely lost
      (Fong and McNamee, 1986). This kind of study also pointed out that phosphatidic
      acid (PA) and cholesterol (Chol) play an important role in preserving the ability
      of this protein to exhibit an optimal channel activity (Fong and McNamee, 1986).
      Furthermore, it has been shown recently that nAChR, itself, induces the formation
      of specific PA-rich lipid domains (Poveda et al., 2002). Because Xenopus oocytes
      incorporate functionally into their plasma membrane nAChRs after intracellular
      injection of liposomes bearing this protein (Morales et al., 1995), the aim of
      this work was to determine the effect of the reconstitution lipid matrix on the
      functional properties of the transplanted nAChRs.

PMID- 17192604
TI  - How three-finger-fold toxins interact with various cholinergic receptors.
AB  - Three-finger-fold toxins, isolated from various snake venoms, are recognized by
      high affinity and various specificities by different nicotinic and muscarinic
      acetylcholine receptors (nAChRs and mAChRs, respectively) present in peripheral,
      as well as central, nervous systems (Karlsson et al., 2000; Servent and Menez,
      2001; Nirthanan and Gwee, 2004). The goal of our studies is (1) to identify, at
      the molecular level, the functional determinants involved in the various
      interaction profiles of nicotinic or muscarinic toxins on their respective
      receptors subtypes, (2) to model some of these toxin-receptor complexes using
      distance constraints obtained from cycle-mutant experiments, and (3) to
      understand how a unique scaffold (the three-finger fold) is able to support these
      different functional profiles and how molecular determinants have been selected
      during the evolution process to create these different specific properties.
      Finally, these structure/function analyses should be exploited to engineer non
      natural peptides with new binding and functional properties useful as
      pharmacological tools or therapeutic agents.

PMID- 17192605
TI  - Acetylcholine-binding proteins: functional and structural homologs of nicotinic
      acetylcholine receptors.
AB  - Acetylcholine-binding protein (AChBP) is a water-soluble protein released from
      molluscan glial cells and modulates ACh-mediated synaptic transmission.
      Acetylcholine-binding protein (AChBP) is a water-soluble homolog of the ligand
      binding domain of nicotinic receptors and other members of the pharmaceutically
      important family of pentameric ligand-gated ion channels (LGICs), GABAA, GABAC, 5
      HT3 serotonin, and glycine receptors. The crystal structure of AChBP from Lymnaea
      stagnalis has become an established model for the extracellular domain of the
      pentameric LGICs, and homology models have been generated to analyze receptor
      ligand interactions. AChBP has pharmacological properties similar to the
      homomeric alpha7 subtype of nicotinic ACh receptors (nAChRs), with relatively
      weak affinity for ACh and a 10-fold higher affinity for nicotine.

PMID- 17192606
TI  - High- and low-sensitivity subforms of alpha4beta2 and alpha3beta2 nAChRs.
AB  - Previous studies in other laboratories have shown that alpha4beta2 nicotinic
      acetylcholine receptor (nAChR) exhibits a biphasic concentration-response
      relationship for ACh with low and high EC50 components, and that the low EC50
      component can be augmented by decreasing the alpha4:beta2 message ratio or
      incubating overnight in nicotine or at low temperature (Zwart and Vijverberg,
      1998; Covernton and Connolly, 2000; Buisson and Bertrand, 2001; Nelson et al.,
      2003; Zhou et al., 2003). In the process of cloning ferret nAChR subunits, we
      found alpha4 and beta2 messages with long untranslated regions (UTRs), as well as
      those with no UTRs. Combinations of these messages revealed that the presence of
      UTRs influenced the ability to exclusively express high-sensitivity subforms of
      alpha4beta2 and alpha3beta2 nAChRs. Injection of oocytes with alpha4 and beta2
      RNAs lacking UTRs (1:1 ratio) led to expression of a biphasic concentration
      response relationship for ACh with EC50 values of 0.5 (high sensitivity) and 114
      microM(low sensitivity). Decreasing the alpha4:beta2 message ratio to as much as
      1:120 increased the high-sensitivity component slightly, but the ACh
      concentration response remained biphasic. In contrast, injection of messages with
      UTRs (1:1 ratio) led to expression of a monophasic concentration response to ACh
      and a high-sensitivity EC50 value of 2.3 microM, as shown in Fig. 1.

PMID- 17192607
TI  - Reorganization of the nicotinic acetylcholine receptor during desensitization
      probed with a photoactivatable agonist.
AB  - The nicotinic acetylcholine receptor (nAChR) from fish electric organs and
      vertebrate neuromuscular junctions is a well-characterized transmembrane
      allosteric protein, composed of four polypeptide chains assembled into a
      heterologous pentamer alpha2betagammadelta, which carries ACh-binding sites and
      contains cation-selective channel-forming elements. Topographical mapping of
      residues contributing to the ligand-binding domain (LBD) of Torpedo nAChR was
      achieved with different site-directed antagonist or agonist probes. Over two
      decades of biochemical investigation led to the identification of three
      discontinuous domains on alpha subunits, with additional residues on gamma and
      delta subunits (Kotzyba- Hibert et al., 2004). This six binding-segment-domain
      model fits quite nicely with the three-dimensional positioning of the homologous
      residues in AChbinding protein (Brejc et al., 2001). However, little is known
      about the structural dynamics of the functioning receptor.

PMID- 17192608
TI  - Coexpression and spatial association of nicotinic acetylcholine receptor subunits
      alpha7 and alpha10 in rat sympathetic neurons.
AB  - Fast excitatory synaptic transmission in sympathetic ganglia is mediated by
      nicotinic acetylcholine receptors (nAChRs). Although it is known that the nAChR
      alpha7-subunit occurs in sympathetic ganglia, the expression of the recently
      cloned subunit alpha10 (Elgoyhen et al., 2001; Lustig et al., 2001; Sgard et al.,
      2002) has not been analyzed. Until now, functional receptors containing alpha10
      subunits have been found only in combination with alpha9-subunits (Elgoyhen et
      al., 2001; Lustig et al., 2001; Sgard et al., 2002). The alpha9-subunit exhibits
      a restricted expression pattern, whereas the alpha10-subunit is expressed more
      widely. This broad distribution resembles more closely that known for subunit
      alpha7 than for subunit alpha9. On this background, we investigated the
      distribution of nAChR subunits alpha7, alpha9, and alpha10 in rat sympathetic
      ganglia and studied a possible interaction between subunit alpha7 and potential
      partners by double-labeling immunofluorescence and fluorescence resonance energy
      transfer (FRET) (Kam et al., 1995; Jares-Erijman and Jovin, 2003).

PMID- 17192609
TI  - Therapeutic potential of novel selective drugs targeting nicotinic acetylcholine
      receptors.
AB  - The potential therapeutic benefit of nicotinic ligands in a variety of
      neurodegenerative pathologies involving the CNS has energized research efforts to
      develop nicotinic acetylcholine receptor (nAChR) subtype-selective ligands
      (Bencherif and Schmitt, 2005). In particular, there has been a concerted effort
      to develop nicotinic compounds with selectivity for CNS nAChRs as potential
      pharmaceutical tools in the management of these disorders. Clinical and
      experimental data demonstrate a central role for alpha7 and alpha4beta2 nAChRs in
      cognitive function, sensory processing, mood, and neuroprotection (Bencherif and
      Schmitt, 2005; Buccafusco et al., 2005). The development of safe alpha7-selective
      ligands has been hampered by their lack of discrimination with hERG channels and
      5-HT3 receptors. We have developed a number of compounds that display nanomolar
      affinity to the alpha7 and/or the alpha4beta2 receptor. Investigation of alpha7
      functional activity showed a full range of activities from antagonists to full
      agonists without any significant activity at the human 5-HT3 receptor, P450
      isozymes, hERG channels, or in the AMES test. Our findings demonstrate that
      potent and highly selective nAChR ligands can be designed.

PMID- 17192610
TI  - Ispronicline: a novel alpha4beta2 nicotinic acetylcholine receptor-selective
      agonist with cognition-enhancing and neuroprotective properties.
AB  - To date, the primary treatments for Alzheimer's disease with proven efficacy have
      been acetylcholinesterase inhibitors that prevent the hydrolysis of acetylcholine
      (ACh) in the synaptic cleft, thereby prolonging its activity. Although these
      agents have some benefit in alleviating cognitive impairment, they have limited
      clinical utility because of insufficient efficacy and marginal tolerability.
      Within the last decade, there has been much experimental support for the use of
      therapeutics that directly target nicotinic ACh receptors (nAChRs) to improve
      cognitive function and slow neurodegenerative disease progression. These findings
      have spurred considerable research efforts to develop ligands selective for
      nAChRs, such as ABT-418 (Arneric et al., 1995), SIB-1553 (Bontempi et al., 2001),
      TC-2403 (Lippiello et al., 1996), and TC-2559 (Bencherif et al., 2000). There is
      abundant evidence that nAChR modulators have the potential to alleviate cognitive
      impairment in demented states. In addition to improving cognitive function, a
      large body of research implicates a role for nAChRs in neuroprotection,
      suggesting potential for disease modification. An impact of nAChR agonists on
      disease progression would provide an advantage over currently available
      treatments for memory loss. The profile of previous nAChR-targeted clinical
      candidates has not been adequate to warrant further development owing to poor
      oral bioavailability, side effects, and/or lack of efficacy. Thus, a challenge in
      nAChR drug design and development has been the reduction of undesirable effects
      that result from activity at specific nAChRs in the CNS and PNS, including
      cardiovascular toxicity, emesis, seizures, and hypothermia.

PMID- 17192611
TI  - Inhibition of carbamate-insensitive acetylcholinesterase by piperonyl butoxide in
      Helicoverpa armigera.
AB  - The cotton bollworm, Helicoverpa armigera, is a cosmopolitan, insecticide
      resistant insect pest of food and fiber (Gunning et al., 1992).
      Acetylcholinesterase (AChE) is the insect target site for carbamate insecticides,
      and H. armigera has developed an insensitive form of AChE as a resistance
      mechanism (Gunning et al., 1996). Insensitive AChE is normally considered an
      intractable resistance mechanism in pests. The methenedioxphenyl compound,
      piperonyl butoxide (PBO), has a long history as an insecticide synergist in the
      control of resistant arthropod pests; it is known to inhibit mono-oxygenases and
      nonspecific esterases (Gunning et al., 1998). This work discusses PBO inhibition
      of AChE in H. armigera and explores synergism.

PMID- 17192612
TI  - Peripheral choline acetyltransferase is expressed by monocytes and upregulated
      during renal allograft rejection in rats.
AB  - Acetylcholine (ACh) has been shown to modulate the function of mononuclear
      leukocytes, both by muscarinic and nicotinic ACh receptors. Acute stimulation of
      lymphocytes with ACh or muscarinic agonists enhances proinflammatory functions,
      whereas chronic application of the ACh agonist nicotine has an anti-inflammatory
      effect (Geng et al., 1996; Kawashima and Fujii, 2003). In macrophages, acute
      treatment with nicotine down-modulates effector functions (Wang et al., 2003,
      2004). ACh regulating leukocytes might originate from the nervous system.
      However, once released, ACh is quickly degraded. Relevant concentrations occur
      only in the direct vicinity of nerve endings. Non-neuronal ACh acting in a
      paracrine or autocrine fashion is more likely to influence immune functions.
      Lymphocytes express all enzymes needed for ACh synthesis, including choline
      acetyltransferase (ChAT). In the rat, alternative splicing generates common ChAT
      and peripheral ChAT (pChAT). Up to now, ChAT expression by monocytes has not been
      demonstrated. We investigate pChAT in monocytes in an experimental model of acute
      renal allograft rejection. Inside the blood vessels of the transplant, huge
      numbers of activated, cytotoxic monocytes accumulate and probably contribute to
      graft destruction (Grau et al., 2001).

PMID- 17192613
TI  - Docosahexaenoic acid supports cell growth and expression of choline
      acetyltransferase and muscarinic receptors in NG108-15 cell line.
AB  - A large body of evidence indicates that adequate intake of polyunsaturated fatty
      acids is essential for brain development in early ontogenesis and positively
      impacts various pathological states connected with aging, as well as other
      neurodegenerative diseases (Jump, 2002; Bazan, 2003; Ruxton et al., 2004). In the
      present experiments, we investigated the possible effects of polyunsaturated
      docosahexanoic acid (DHA [22:6, n = 3]) on the expression of cholinergic
      phenotype-represented by choline acetyltransferase (ChAT) activity and a number
      of surface muscarinic receptors-as well as on cell growth in the cholinergic cell
      line NG108-15(Hamprecht, 1977; Hamprecht et al., 1985). However, chemical
      composition of different batches of sera is neither stable nor defined, and this
      fact complicates investigations on in vitro effects of substances that are
      natural constituents of serum. To avoid this restraint we employed defined medium
      in which fatty acid-free bovine albumin as a carrier of DHA replaced serum.
      Growth of most cell lines, as well as cells in primary cultures, depends strictly
      on the presence of serum in growth medium. As expected, withdrawal of serum
      resulted in growth arrest exemplified by a decrease in protein content compared
      with control cells grown in the presence of serum and also caused a decrease in
      ChAT activity (Fig. 1, lower left). DHA, at a concentration of 10 mumol/L,
      largely prevented both growth arrest in defined medium with fatty acid-free
      bovine albumin as a carrier of DHA and the attenuation of ChAT activity. DHA at
      concentrations 10 times higher had no further effect. At a concentration of 100
      mumol/L, DHA also significantly increased the number of surface muscarinic
      receptors compared with cells grown in serum-containing as well as serum-free
      medium (Fig. 1, upper right). These data demonstrate the ability of DHA at low
      micromolar concentrations to support cell growth and expression of ChAT activity.
      Although it is not possible to stipulate a mechanism of action on the expression
      of ChAT and muscarinic receptors, a plausible explanation could be prevention of
      apoptosis, evidenced by a sharp decrease in executive caspase-3 activity (Fig. 1,
      lower right). Apoptosis is a process with a high requirement for energy. An
      improved metabolic state of cells consequent to suppression of apoptosis might
      thus better fulfill requirements for protein synthesis and targeting.

PMID- 17192614
TI  - Expression of MuSK in in vitro-innervated human muscle.
AB  - Unlike rodent or avian muscle, which forms clusters of acetylcholine receptors
      (AChRs) on its surface, exhibits cross striations, and contracts spontaneously
      even if cultured in the absence of the nerve, human muscle must be innervated to
      reach such differentiation level under in vitro conditions (Kobayashi and
      Askanas, 1985; Mars et al., 2001). Because it is known that AChR clustering and
      other aspects of neuromuscular junction (NMJ) formation necessitate the
      activation of muscle-specific kinase (MuSK), one explanation of this inability of
      human muscle is that it has no MuSK or that it cannot be activated in the absence
      of the nerve. To test this hypothesis we analyzed cultured human muscle for the
      expression of MuSK at two stages of differentiation: postfusion myotube and
      innervated, contracting myotube. Analyses were carried out at the mRNA level, as
      no reliable anti-MuSK antibodies are available for the immunocytochemical
      demonstration of MuSK in cultured human muscle. The presence of MuSK, however,
      can be tested indirectly, as it can be activated in the absence of the nerve
      simply by growing muscle culture on laminin coating (Kummer et al., 2004). In the
      second part of our study, we therefore tested human myotubes for the presence and
      activation of MuSK by exposing them to laminin coating and by analyzing them
      afterwards for the areas of postsynaptic differentiation typical for NMJ
      formation.

PMID- 17192616
TI  - Effects of acetylcholinesterase gene silencing on its activity in cultured human
      skeletal muscle.
AB  - In spite of several reports demonstrating that acetylcholinesterase (AChE [EC
      3.1.1.7]) expression is importantly regulated at the level of its mRNA, we still
      know little about the relationship between AChE mRNA level and the level of
      mature, catalytically active enzyme in the cell. Better insight into this
      relationship is, however, essential for our understanding of the molecular
      pathways underlying AChE synthesis in living cells. We have approached this
      problem previously (Grubic et al., 1995; Brank et al., 1998; Mis et al., 2003;
      Jevsek et al., 2004); however, recently introduced small interfering RNA (siRNA)
      methodology, which allows blockade of gene expression at the mRNA level, opens
      new possibilities in approaching the AChE mRNA-AChE activity relationship. With
      this technique one can eliminate AChE mRNA in the cell, specifically and at
      selected times, and follow the effects of such treatment at the mature enzyme
      level. In this study we followed AChE activity in siRNA-treated cultured human
      myoblasts. Our aim was to find out how the temporal profile of the AChE mRNA
      decrease is reflected at the level of AChE activity under normal conditions and
      after inhibition of preexisting AChE by diisopropyl phosphorofluoridate
      (DFP).AChE activity was determined at selected time intervals after siRNA
      treatment in both myoblast homogenates and in culture medium to follow the
      effects of siRNA treatment at the level of intracellular AChE synthesis and at
      the level of AChE secreted from the cell.

PMID- 17192615
TI  - Microarray screen for synaptic genes in the neuromuscular junction.
AB  - The formation of neuromuscular synapses requires a complex exchange of signals
      between motor neurons and skeletal muscle fibers. Essential for the formation of
      neuromuscular junction (NMJ) is the activation of MuSK, a muscle-specific
      receptor tyrosine kinase (DeChiara et al., 1996). In mice lacking MuSK, motor
      axons fail to stop and differentiate, acetylcholine receptors (AChRs) fail to
      cluster, and AChR genes are expressed uniformly in muscle (DeChiara et al., 1996;
      Gautam et al., 1996). The retrograde signals for presynaptic differentiation are
      not known. Because synapse-specific transcription, like presynaptic
      differentiation, is MuSK-dependent, it is possible that retrograde signals for
      presynaptic differentiation might be encoded by genes that are expressed
      preferentially by synaptic nuclei. To identify such synapse-specific genes we
      screened Affymetrix microarrays with RNA from the dissected, synapse-enriched,
      and extrasynaptic regions of skeletal muscle and further studied those genes that
      encode for the secreted or cell-surface proteins.

PMID- 17192617
TI  - Chick acetylcholinesterase promoter regulation.
AB  - In vertebrate neuromuscular junction, acetylcholinesterase (AChE) is colocalized
      with acetylcholine receptor (AChR). This synaptic expression of AChE requires
      precise regulation of the AChE gene. However, the gene regulation pattern has
      species variation. Previous studies (Massoulie, 2002) indicated that AChE
      activities in muscles decreased in rat but increased in chicken after
      denervation. The spatial arrangement of regulatory elements in promoters among
      animals therefore might be varied. The genomic structures of AChE have been
      analyzed in Torpedo, mouse, rat, and human but not in chick, and the molecular
      mechanism(s) responsible for contrary regulation of AChE between chick and mammal
      has been proposed (Choi et al., 2001) but not fully understood. Here, we report
      the cloning of the chick AChE promoter, the regulation of which is being
      characterized.

PMID- 17192618
TI  - Engineered site-directed labeling of nicotinic acetylcholine receptors using
      reactive epibatidine derivatives: appraisal of epibatidine-docking models in
      neuronal and muscular receptors.
AB  - We developed an engineered site-directed labeling method (Foucaud et al., 2001)
      to investigate ligand receptor interactions on the acetylcholine (ACh)- binding
      site of nicotinic acetylcholine receptors (nAChRs). The method uses cysteine
      receptor mutants, together with cysteine-reactive ligand analogs, to generate a
      site-directed covalent reaction within the binding site. We selected epibatidine
      (EPB) as a prototypical ligand, acting at all types of nAChRs with sufficient
      affinity to allow this study. Accordingly, we synthesized three cysteine-reactive
      derivatives, all modified at the C-3 of the pyridine ring of the alkaloid with
      NCS; -NHCOCH2Cl, and -CH2Cl groups, respectively (Fig. 1). The binding properties
      have been established on rat brain, alpha7-5HT3 chimera, and Torpedo membranes,
      respectively, whereas the functional properties were tested on alpha4beta2 and
      alpha7 receptor expressed in oocytes and Cys-less muscular receptor expressed in
      HEK cells (Sakr et al., 2005).

PMID- 17192619
TI  - Rafts are required for acetylcholine receptor clustering.
AB  - Cholesterol-sphingolipid microdomains, or lipid rafts, are major regulators of
      molecular interactions in membrane organization. Because lipid rafts can move
      laterally and cluster into larger patches, they have been proposed to play a role
      in the redistribution of specific molecules to specialized cellular structures.
      Rafts have been shown to favor formation and maintenance of synaptic receptor
      clusters in neurons of the central nervous system. However, little is known about
      their role in formation of the neuromuscular junction (NMJ). To determine whether
      lipid rafts are involved in acetylcholine receptor (AChR) cluster formation and
      stabilization in myogenic cells, two standard tools were employed: (1)
      Perturbation of lipid rafts by drugs that deplete membrane cholesterol was
      carried out to verify that cholesterol is required for AChR clustering in agrin
      treated C2C12 myotubes; and (2) detergent resistance of lipid-ordered domains was
      also used to demonstrate that AChRs, as well as key components of the
      postsynaptic membrane of the NMJ, are associated with rafts.

PMID- 17192620
TI  - Buprofezin inhibits acetylcholinesterase activity in B-biotype Bemisia tabaci.
AB  - B-biotype Bemisia tabaci is a severe insect pest worldwide in many ornamental,
      agricultural, and horticultural industries. Control of this insect is hampered by
      resistance to many acetylcholinesterase (AChE)-inhibiting insecticides, such as
      organophosphates and carbamates. Consequently, insect growth regulators such as
      buprofezin, which act by inhibiting chitin synthesis, are being investigated for
      use against B-biotype B. tabaci in Australia. This study discusses the effects of
      buprofezin on B. tabaciAChE.

PMID- 17192621
TI  - Vesicular calcium transport shapes rapid acetylcholine secretion.
AB  - Rapid secretion relies on the occurrence of spike-like Ca2+ transients in active
      zones (Llinas et al., 1992; Yazejian et al., 2000; Dunant and Bloc, 2003).
      Presynaptic Ca2+ nanodomains are to be restricted both in time and in space as to
      assure rapid onset and termination of transmitter release (Llinas et al., 1992;
      Pozzan et al., 1994; Yazejian et al., 2000; Dunant and Bloc, 2003). A very fast
      Ca2+-buffering mechanism should allow Ca2+ rise above approximately 100 microM
      for less than approximately 250 micros and then rapid reduction of Ca2+ to
      subthreshold levels of release (Llinas et al., 1992; Pozzan et al., 1994;
      Yazejian et al., 2000; Dunant and Bloc, 2003). Swift Ca2+ clearance by vesicular
      Ca2+/H+ antiport as a low-affinity, high-capacity extrusion mechanism was
      postulated in the past (Pozzan et al., 1994; Dunant and Bloc, 2003). We
      demonstrated pH gradient (DeltapH)-dependent Ca2+ uptake by mammalian brain
      synaptic vesicles (Goncalves et al., 1998, 2000). Moreover, this antiport
      activity is effective at [Ca2+] ranging from approximately 100 to 800 microM
      (max. at approximately 500 microM) (Goncalves et al., 1998, 2000). We now show
      that the time course of acetylcholine (ACh) secretion in Torpedo
      neuroelectrocytic synapse is modified by bafilomycin A1 (baf.), which compromises
      antiport activity. Along with this mechanism, synaptic vesicles also have a P
      type Ca2+ ATPase, exhibiting half-maximal activation for 0.6 microM Ca2+
      (Goncalves et al., 2000). Here, we demonstrate the role of P-type Ca2+ ATPase in
      preventing desensitization of the release mechanism by inhibiting it with
      orthovanadate.

PMID- 17192622
TI  - Acetylcholine and regulation of gene expression in developing systems.
AB  - One of the major questions related to nervous system development is the
      identification of signals directing neuronal populations to specific phenotypes
      (e.g., cholinergic, adrenergic, or peptidergic neurons) and involved in cell-to
      cell interactions. Although neurotrophins have long been known for their function
      in development, the neurotransmitter role as modulator of gene expression and
      differentiation has been recognized only recently. Evidence for the ability of
      various neurotransmitter molecules to influence various cellular events during
      neuron differentiation has been reported in several systems (Lauder and Schambra,
      1999). We have focused our interest on acetylcholine (ACh) and its possible role
      in the regulation of neuron-specific gene expression, using different
      experimental systems: (1) neuroblastoma cell lines, as a model of cholinergic
      neuron differentiation; (2) dorsal root ganglia (DRG) sensory neurons, which
      activate the expression of a cholinergic system early in development, in spite of
      their peptidergic or aminoacidergic neurotransmission; and (3) primary cultures
      of Schwann cells. Data obtained on each system will be described briefly.

PMID- 17192623
TI  - Thymus acetylcholinesterase activity is reduced in mice with congenital muscular
      dystrophy.
AB  - Lama2dy mice constitute an animal model for congenital muscular dystrophy (CMD)
      by merosin (laminin alpha2-chain) deficiency. This pathology affects the
      properties of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) of
      mouse skeletal muscle and nerves (Moral-Naranjo et al., 1999, 2002). AChE and
      BChE are involved through catalytic and noncatalytic actions in multiple
      processes, such as hydrolysis of acetylcholine (ACh), morphogenesis,
      hematopoiesis, and tumorigenesis (Soreq and Seidman, 2001). AChE and BChE
      molecules can be globular (G1, G2, and G4) or asymmetric forms (A4, A8, and A12)
      (Massoulie, 2002), and G molecules can show amphiphilic (detergent-interacting,
      GA) or hydrophilic (GH) behavior. AChE catalytic subunits are encoded by three
      mRNAs (T, H, or R) generated by alternative splicing. The presence of AChE in
      lymphoid tissues (Rossi et al., 1991; Nieto-Ceron et al., 2004), the role of
      immune responses in muscular dystrophy (Spencer and Tidball, 2001), the
      abnormalities of Lama2dy thymus (Magner et al., 2000), and the role of ACh in
      thymocyte function (Kawashima and Fujii, 2000) prompted us to investigate thymus
      AChE and the possible effect of merosin deficiency on it.

PMID- 17192624
TI  - Acetyl- and butyrylcholinesterase activities decrease in human colon
      adenocarcinoma.
AB  - Apart from the hydrolysis of acetylcholine (ACh), acetyl- (AChE) and
      butyrylcholinesterase (BChE), through noncatalytic mechanisms, intervene in
      hematopoiesis, morphogenesis, and neurogenesis (Layer and Willbold, 1995; Soreq
      and Seidman, 2001). Cholinesterase (ChE) molecules occur as globular (G1, G2, and
      G4) and asymmetric (A4, A8, and A12) forms (Legay, 2000; Massoulie, 2002). The G
      species might display amphiphilic (GA) or hydrophilic (GH) properties (Perrier et
      al., 2002). The involvement of ChEs in tumorigenesis is supported by the
      measurement of ChE activity in tumors (Garcia-Ayllon et al., 2001; Ruiz-Espejo et
      al., 2003), the amplification of ChE genes in leukemias and ovarian tumors, and
      the relationship between the expression of AChE and the aggressiveness of
      astrocytomas(Perry et al., 2002). This research was undertaken to determine
      whether ChE activity is altered in gut carcinomas.

PMID- 17192625
TI  - Nicotinic acetylcholine receptors containing subunits alpha3 and alpha5 in rat
      nociceptive dorsal root ganglion neurons.
AB  - Nociceptive primary afferent neurons carry nicotinic acetylcholine receptors
      (nAChRs). Using RTPCR, mRNAs for all alpha-subunits have been identified in rat
      dorsal root ganglia (DRG) (Genzen et al., 2001; Lips et al., 2002), but the
      responses of nociceptive neurons to nicotine are not uniform and the cellular
      distribution of nAChRs within DRG, in general, and among functionally different
      subtypes of primary afferent neurons, in particular, are only partially resolved
      (Rau et al., 2005). These diverse actions might suggest the presence of various
      nAChR isoforms that are operative under different conditions. The present study
      was aimed to extend previous studies on nAChRs that contain subunits alpha4,
      alpha7, and alpha10 in providing data for alpha3- and alpha5-subunit-containing
      nAChRs (Haberberger et al., 2004; Papadopolou et al., 2004). To this end, calcium
      imaging and double-labeling immunofluorescence with nAChR alpha-subunit-specific
      antibodies, in combination with markers for nociceptive neurons (TRPV1, I-B4),
      were applied.

PMID- 17192626
TI  - A comparison between acetylcholine-like action potentials and square depolarizing
      pulses in triggering calcium entry and exocytosis in bovine chromaffin cells.
AB  - Depending on experimental conditions, cell model, and pattern and type of
      depolarizing stimuli, the relationship between calcium entry ([Ca2+]c) and the
      release of neurotransmitters and hormones varies from exponential (power of 3-4)
      to near linear (power of 1.5) or linear function. Here, we present a study using
      the more physiological stimulation pattern based on acetylcholine (ACh)-like
      action potentials, in voltage-clamped bovine chromaffin cells, with the
      perforated-patch configuration of the patch-clamp technique and 2 mM
      extracellular calcium. Trains of ACh-like action potentials or square
      depolarizing pulses of increasing length were applied, and calcium currents
      (ICa), total calcium entry (QCa), and exocytosis (DeltaCm) measured.

PMID- 17192628
TI  - Neuroprotection by nicotine in hippocampal slices subjected to oxygen-glucose
      deprivation: involvement of the alpha7 nAChR subtype.
AB  - Nicotine (NIC) is neuroprotective against glutamate and hypoxia-induced
      neurotoxicity, preventing neuronal death and apoptosis in primary neuronal
      cultures. This effect is mediated by activation of both alpha7 and alpha4beta2
      subtypes of nicotinic receptors for acetylcholine (nAChR) (Kaneko et al., 1997;
      Hejmadi et al., 2003). Furthermore, it seems that activation of alpha7 nAChR is
      the mechanism by which galantamine protects against thapsigargin and beta-amyloid
      induced cell death (Arias et al., 2004), as well as in neuroprotection exerted by
      NIC against tumor necrosis factor alpha (Gahring et al., 2003). In this context
      we studied possible protection produced by NIC in an oxygen-glucose deprivation
      (OGD) model of rat and mouse hippocampal slices. The involvement of alpha7 nAChR
      in neuroprotection was proved by using wild-type and alpha7 knockout (KO) mice.

PMID- 17192627
TI  - Desensitized nicotinic receptors that, however, afford cytoprotection in bovine
      chromaffin cells.
AB  - Neuronal nicotinic receptors for acetylcholine (nAChRs) are among the ionotropic
      receptors that suffer the most desensitization upon prolonged exposure to their
      agonists. This is particularly true for the alpha7 subtype of nAChRs, although
      alpha3beta4 receptors also suffer quick desensitization. This study was planned
      to test the hypothesis that even after suffering desensitization, a given nAChR
      might still afford cell protection against a noxious stimulus. Of the many
      agonists developed for nAChRs, we selected the poorly desensitizing ligand
      dimethylphenylpiperazinium (DMPP) (Britt and Brenner, 1997) and the highly
      desensitizing agent epibatidine (EPB) (Marks et al., 1996). We have measured
      nAChR currents, catecholamine secretory responses, and changes of [Ca2+]c
      elicited by stimulation of nAChRs with DMPP or EPB. We have also investigated
      cytoprotection elicited by DMPP and EPB against the cytotoxic effects of
      veratridine in bovine chromaffin cells.

PMID- 17192629
TI  - Identification of two critical residues within the Cys-loop sequence that
      determine fast-gating kinetics in a pentameric ligand-gated ion channel.
AB  - Pentameric ligand-gated ion channels (LGICs) are fast-gating receptors,
      represented by cationic nicotinic acetylcholine (nAChR) and serotonin (5HT3R)
      receptors, and by anionic GABA and glycine (GlyR) receptors. Because of a highly
      conserved sequence of 13 amino acids flanked by two canonical cysteine residues
      shared by all members of the family, these receptors are also known as the Cys
      loop family. These receptors are allosteric transmembrane proteins made of five
      identical (or not) subunits arranged (pseudo) symmetrically around a central ion
      pore in the membrane. In nAChR, upon ACh binding, the receptor interconverts into
      discrete allosteric states, with each state corresponding to a different
      physiological state: resting (closed), active (open), and desensitized (closed).

PMID- 17192630
TI  - Altered glycosylation of acetylcholinesterase in the Creutzfeldt-Jakob
      cerebrospinal fluid.
AB  - Several neurodegenerative disorders present deficiencies in the cholinergic
      system. Scarce research on prion encephalopathies has examined the levels of
      cholinergic pathway-related enzymes. Acetylcholinesterase (AChE) is expressed as
      several molecular forms. The potential importance of these variants is increased
      by the possibility that AChE has roles other than acetylcholine hydrolysis. We
      investigated the levels of AChE, its molecular forms, and glycosylation in the
      cerebrospinal fluid (CSF) from Creutzfeldt-Jakob disease (CJD) patients.

PMID- 17192631
TI  - Role of acetylcholine and muscarinic receptors in serotonin-induced
      bronchoconstriction in the mouse.
AB  - For the murine trachea, it has been reported that constriction evoked by
      serotonin (5-HT) is largely dependent on acetylcholine (ACh) released from the
      epithelium, owing to the sensitivity of the 5-HT response to epithelium removal,
      sensitivity to atropine, and insensitivity to tetrodotoxin (Moffatt et al.,
      2003). Consistent with this assumption, the respiratory epithelium contains ACh,
      its synthesizing enzyme, and the high-affinity choline transporter CHT1
      (Reinheimer et al., 1996; Pfeil et al., 2003; Proskocil et al., 2004). Recently,
      we demonstrated that ACh can be released from non-neuronal cells by
      corticosteroid-sensitive polyspecific organic cation transporters (OCTs), which
      are also expressed by airway epithelial cells (Lips et al., 2005). Hence, we
      proposed that 5-HT evokes release of ACh from epithelial cells via OCTs and that
      this epithelial-derived ACh induces bronchoconstriction. We tested this
      hypothesis in a well-established model of videomorphometric analysis of bronchial
      diameter in precision-cut murine lung slices utilizing epithelium removal to
      assess the role of the epithelium, OCT mouse knockout (KO) strains to assess the
      role of OCT isoforms, and muscarinic receptor M2/M3 double-KO mice to assess the
      cholinergic component of 5-HT induced bronchoconstriction, as bronchi of this
      strain are entirely unresponsive to cholinergic stimulation(Struckmann et al.,
      2003).

PMID- 17192632
TI  - Muscarinic receptors are affected by corticotropin-releasing hormone and c-fos
      gene disruptions: is there a mutual connection to adrenoceptors?
AB  - In the last decade, progress in gene disruption technology has allowed the study
      of the effects of the single-gene knockout (KO) on different molecules involved
      in the signaling cascade activated via muscarinic receptors. Many KO mice
      targeting muscarinic receptors have been developed, that is, all (M1-M5)
      muscarinic receptor KO mice (Wess, 2003) and acetylcholinesterase (AChE) KO
      mice(Xie et al., 2000). Recently, we have shown that these (AChE-/-) mice not
      only reveal changes in the number of muscarinic receptors in the heart, lung,
      cortex, and cerebellum but also in the number of adrenoceptors (Teplicky et al.,
      2004). Next, we studied whether the disruption of corticotropin-releasing hormone
      (CRH) or c-Fos could affect the properties of muscarinic receptors and
      adrenoceptors in the lungs and hearts of mice. The effects of immobilization
      stress in CRH KO animals were also studied.

PMID- 17192633
TI  - A model for short alpha-neurotoxin bound to nicotinic acetylcholine receptor from
      Torpedo californica.
AB  - Short- and long-chain alpha-neurotoxins from snake venoms are potent blockers of
      nicotinic acetylcholine receptors (nAChRs). Short alpha-neurotoxins consist of 60
      62 amino acid residues and include 4 disulfide bridges, whereas long alpha
      neurotoxins have 66-75 residues and 5 disulfides. The spatial structure of these
      toxins is built by three loops, I-III "fingers," confined by four disulfide
      bridges; the fifth disulfide of long-chain alpha-neurotoxins is situated close to
      the tip of central loop II. An accurate knowledge of the mode of alpha-neurotoxin
      nAChR interaction is important for rational design of new nAChR agonists and
      antagonists for medical purposes. Ideas on the topography of toxin-nAChR
      complexes were based until recently on nAChR interactions with selectively
      labeled alpha-neurotoxins, mutations in toxins, nAChR, or both. Recently, crystal
      structures have been solved for the Torpedo marmorata nAChR (4A[Unwin, 2005]) and
      for the acetylcholine-binding protein (AChBP) complexed with mollusk alpha
      conotoxin (2.4 A[Celie et al., 2005]) or alpha-cobratoxin, long-chain alpha
      neurotoxin (4 A [Bourne et al., 2005]). However, there were no angstrom
      resolution models for complexes of short-chain alpha-neurotoxins. Here, we report
      the model of the Torpedo californica nAChR extracellular domain complexed to a
      short-chain alpha-neurotoxin II (NTII) from Naja oxiana cobra venom.

PMID- 17192634
TI  - Structural dynamics of the acetylcholine binding protein: hydrodynamic and
      fluorescence anisotropy decay analyses.
AB  - Recently, several crystal structures have become available for the acetylcholine
      binding protein (AChBP), a soluble nicotinic receptor extracellular domain (ECD)
      surrogate in its unliganded state, as well as in complex with agonists and
      antagonists. In these studies we sought to better understand how the dynamic
      receptor ECD surrogate from Lymnaea stagnalis behaves in solution, with and
      without ligand present. To accomplish this, we studied first the overall size and
      shape of the macromolecule, using hydrodynamic (sedimentation) techniques, and
      how these parameters were perturbed by the binding of various ligands. Analysis
      of sedimentation and frictional coefficients indicated that bound alpha
      bungarotoxin (a three-fingered peptide toxin) is not oriented as a rigid body
      extending radially from the cylinder of the protein but, rather, that the toxin
      has inherent segmental flexibility such that it has a limited effect on the
      frictional coefficient of the pentamer. These results were supported by
      anisotropy decay studies of segmental motion of the toxin when free in solution
      and bound to AChBP. We selected the C-loop of AChBP, a region where ligand
      elicited changes in conformation are substantial, and studied neighboring regions
      at higher resolution in terms of alpha-carbon backbone flexibility by decay of
      fluorescence anisotropy. Several single cysteine substitutions were labeled
      selectively with the fluorescent probe MTS-4-fluorescein. The covalently
      conjugated mutants, at two sites on the C-loop (S182C, D194C), and one on the
      opposing side of the subunit interface (Y164C), revealed similar alpha-carbon
      backbone flexibility with no ligand present but underwent distinctive changes in
      backbone mobility after ligand binding. At the sites we studied on the C-loop,
      agonists always segregated together in terms of their effects on backbone
      mobility; however antagonists did not reveal a similarly conserved pattern. At
      Y164C, however, we did observe segregating effects on backbone flexibility
      between agonists and antagonists. As a structural and functional surrogate of the
      nicotinic acetylcholine receptor, the AChBP reveals ligand-mediated changes in
      conformation, mimicking that of the receptor.

PMID- 17192635
TI  - Readthrough acetylcholinesterase expression remains minor after stress or
      exposure to inhibitors.
AB  - The gene of mammalian acetylcholinesterase (AChE) generates multiple molecular
      forms, by alternative splicing of its transcripts and association of the tailed
      variant (AChET) with structural proteins. In the mammalian brain, the major AChE
      species consists of AChET tetramers anchored to the cell membrane of neurons by
      the PRiMA protein (Perrier et al., 2002). Stress and anticholinesterase
      inhibitors have been reported to induce rapid and long-lasting expression of the
      readthrough variant (AChER) in the mouse brain (Kaufer et al., 1998). In the
      readthrough transcript, there is no splicing after the last exon encoding the
      catalytic domain, so that the entire alternatively spliced 3' region is
      maintained. It encodes a C-terminal peptide with no specific interaction
      properties: COS cells transfected with AChER produce a soluble, nonamphiphilic
      monomeric form. We quantified AChER and total AChE expression in the mouse brain
      after an immobilization stress and after heat shock in neuroblastoma cells, and
      compared the observed effects with those induced by irreversible AChE inhibition
      (Perrier et al., 2005).

PMID- 17192636
TI  - Alpha-conotoxin analogs with enhanced affinity for nicotinic receptors and
      acetylcholine-binding proteins.
AB  - Alpha-conotoxins, neurotoxic peptides from poisonous Conus marine snails, can be
      subdivided into several groups targeting distinct subtypes of nicotinic
      acetylcholine receptors (nAChRs). Such alpha-conotoxins as, for example, GI, MI,
      or SIA potently block muscle-type nAChRs from muscles and from the electric organ
      of Torpedo ray, whereas others target distinct neuronal nAChRs: alpha-conotoxins
      ImI and PnIB block pentaoligomeric alpha7 nAChRs, and alpha-conotoxins MII or
      PnIA inhibit heteromeric nAChRs made of combinations of alpha3 or alpha6 subunits
      with beta2 subunit. alpha-Conotoxins interact with N-terminal extracellular
      ligand-binding domains of nAChRs and are indispensable tools for distinguishing
      various subtypes of AChRs at normal and pathological states. Although many alpha
      conotoxins have been isolated from Conus venoms, there is still a great need in
      more potent and selective tools, which in principle can be obtained by design and
      synthesis of novel alpha-conotoxin analogs.

PMID- 17192637
TI  - Gene transfer of acetylcholinesterase protects the knockout mouse from the
      toxicity of DFP.
AB  - Acetylcholinesterase (AChE) has a clear role in nerve impulse transmission.
      Organophosphorus esters are highly toxic chemicals used as pesticides, fire
      retardants, plasticizers, and chemical warfare agents. The acute toxicity of
      organophosphorus poisons is attributed to inhibition of AChE in nerve synapses.
      This leads to seizures, respiratory arrest, and death. Our goal was to find a new
      therapeutic for protection against the toxicity of organophosphates (OPs). We
      investigated the feasibility of using a gene therapy vector to deliver AChE over
      long time periods and in quantities sufficiently high to provide protection
      against diisopropylfluorophosphate (DFP) toxicity. We used the AChE-/- mouse for
      these studies because this mouse has no endogenous AChE activity (Xie et al.,
      2000). Any AChE activity found in tissues could only come from the viral vector.

PMID- 17192638
TI  - Enhancement of secretion by threshold nicotinic stimulation in bovine chromaffin
      cells.
AB  - Synaptic release of neurotransmitters displays activity-dependent changes such as
      enhancement (facilitation, augmentation, or potentiation) or diminution
      (depression), which have been studied widely because of their implication in
      synaptic efficacy, neuronal plasticity, and formation and consolidation of
      learning and memory. Some of these types of modulation of secretion displayed by
      neurons are also present in neuroendocrine chromaffin cells, for instance,
      facilitation or augmentation, which seem to be related to mild changes in the
      transients of cytosolic concentration of calcium ([Ca2+]i) and the degree of
      refilling of the primed vesicle pool (Zucker, 1996; Neher, 1998). Desensitized
      nicotinic acetylcholine receptors (nAChRs) and their possible role in this short
      term synaptic plasticity was investigated in populations of bovine chromaffin
      cells.

PMID- 17192639
TI  - Alpha7 nicotinic acetylcholine receptor expression in Alzheimer's disease:
      receptor densities in brain regions of the APP(SWE) mouse model and in human
      peripheral blood lymphocytes.
AB  - The brains of people with Alzheimer's disease (AD) display several characteristic
      pathological features, including deposits (plaques) of beta-amyloid 1-42 (Abeta1
      42), intraneuronal accumulations (tangles) of hyperphosphorylated tau,
      degeneration of the basal forebrain cholinergic pathway, and gliosis. Abeta1-42
      plaques develop in specific brain regions, including hippocampus and cortex, as
      well as in the vasculature. Abeta1-42 might promote neurodegeneration through the
      induction of free radicals and disruption of Ca2+ homeostasis, giving rise to the
      symptoms of AD. Abeta1-42 interacts with the alpha7 subtype of the nicotinic
      acetylcholine receptor (alpha7 nAChR), which is widely expressed throughout the
      central and peripheral nervous systems, as well as in several nonneuronal loci,
      such as epithelial cells, lymphoid tissues, and peripheral blood lymphocytes.
      Western blot and autoradiographic analyses indicate that the alpha7 nAChR subunit
      protein is up-regulated in human brain samples from Alzheimer patients, as well
      as in animal models of AD (Dineley et al., 2001; Bednar et al., 2002), and might
      be involved in nicotine-mediated reduction of Abeta1-42 deposition (Hellstrom et
      al., 2004), although the nature of this relationship remains ill-defined. We have
      undertaken a semiquantitative histological evaluation of alpha7 nAChR expression
      in a mouse model of AD pathology, as well as a comparison of alpha7 nAChR levels
      in lymphocytes from AD patients and control subjects.

PMID- 17192640
TI  - Dual binding site acetylcholinesterase inhibitors: potential new disease
      modifying agents for AD.
AB  - The therapeutic potential of acetylcholinesterase (AChE) inhibitors has been
      strengthened recently by evidence showing that besides their role in cognitive
      function, they might contribute to slow down the neurodegeneration in Alzheimer's
      disease (AD) patients. It is known that AChE exerts secondary noncholinergic
      functions, related to its peripheral anionic site, in cell adhesion and
      differentiation, and recent findings also support its role in mediating the
      processing and deposition of beta-amyloid (Abeta) peptide. AChE is one of the
      proteins that colocalizes with Abeta peptide deposits in the brain of AD patients
      and promotes Abeta fibrillogenesis by forming stable AChEA beta complexes.
      Additionally, it has also been postulated that AChE binds through its peripheral
      site to the Abeta nonamyloidogenic form and acts as a pathological chaperone
      inducing a conformational transition to the amyloidogenic form (Inestrosa et al.,
      1996; Bartolini et al., 2003). Anew series of dual binding site AChE inhibitors
      has been designed and synthesized as new potent AChE inhibitors, which might
      simultaneously alleviate cognitive deficits and behave as disease-modifying
      agents by inhibiting Abeta peptide aggregation through binding to both catalytic
      and peripheral sites of the enzyme.

PMID- 17192641
TI  - Effect of acetylcholinesterase inhibitors on AChE-induced PrP106-126 aggregation.
AB  - Transmissible spongiform encephalopaties are caused by an extracellular surface
      protein, the scrapie prion protein (PrPsc), which is an aberrant form of normal
      and functional cellular PrP (PrPc). The pathological hallmarks of these diseases
      are the accumulation and deposition of PrPsc in the form of amyloid fibrils in
      the central nervous system (Tateishi et al., 1988), similar to amyloid-beta
      (Abeta) protein in Alzheimer's disease (AD). In some patients, Abeta and prion
      pathology can coexist (Hainfellner et al., 1998), and a common spatial pattern of
      protein deposition has been described (Armstrong et al., 2001). In addition, it
      is well-known that acetylcholinesterase (AChE) colocalizes with Abeta deposits of
      brains in AD patients and accelerates assembly of Abeta peptides through the
      peripheral site of the enzyme (Inestrosa et al., 1996). The aim of the present
      study was to analyze time course and concentration dependence of the AChE
      proaggregating effect on synthetic peptide-spanning residues 106-126 of human PrP
      (PrP106-126) and the reversion of this effect by different AChE inhibitors
      (AChEIs).

PMID- 17192642
TI  - Phenotype comparison of three acetylcholinesterase knockout strains.
AB  - The phenotypes of three mouse strains that carry the acetylcholinesterase
      knockout (AChE KO) mutation have been compared. The AChE KO mouse was developed
      from embryonic stem (ES) cells, originating from a 129/Sv blastocyst. Animals
      generated from strain 129/Sv suffer from dysgenesis of the corpus callosum and
      possibly a number of other neuroanatomical deficiencies. To determine the
      contribution of background genes to phenotype, 129/Sv AChE heterozygote (AChE+/-)
      mice were backcrossed 10 generations with wild-type inbred C57/BL6 (C57) mice and
      with wild-type outbred CD1(R) mice. AChE-/- mice in strains C57 and CD1died
      during seizures before postnatal day (P) 21, whereas mice in strain 129/Sv lived
      to adulthood.

PMID- 17192643
TI  - Markers of organophosphate exposure in human serum.
AB  - The goal of this work is to identify novel serum proteins that are labeled with
      organophosphates (OPs) and to create a protocol for identification using mass
      spectroscopy. The use of OP-labeled proteins for identification of exposure is
      useful because such proteins will remain in circulation for weeks (Van Der Schans
      et al., 2004). Currently, both butyrylcholinesterase (BChE) and albumin have been
      shown to bind OPs in blood. Peeples et al. (2005) showed that albumin is labeled
      by OPs, specifically 6-Nbiotinylaminohexyl isopropyl phosphorofluoridate
      hemihydrate, in living mice. Albumin is the major protein in human serum, and its
      reaction with OPs tends to overwhelm the identification of other proteins. In
      vitro studies of human serum require removal of the serum albumin without
      depleting the less abundant proteins. Following this step, identifying the
      remaining proteins is simply a matter of labeling the proteins with an OP,
      separating the labeled from nonlabeled proteins, and using Q-trap mass
      spectrometry for identification.

PMID- 17192644
TI  - Stoichiometry and pharmacology of two human alpha4beta2 nicotinic receptor types.
AB  - The alpha4beta2 nicotinic acetylcholine receptor (nAChR) is the most abundant
      nAChR subtype in the brain, where it forms the high-affinity binding site for
      nicotine. The alpha4beta2 nAChR belongs to a gene family of ligand-gated ion
      channels that also includes muscle nAChRs, GABAA receptors, and glycine receptors
      and that assembles into pentameric structures. alpha4 and beta2 nAChR subunits
      expressed heterologously in Xenopus laevis oocytes assemble into a mixture of
      high- and low-affinity functional receptors, giving rise to biphasic ACh
      concentration-response curves (Zwart and Vijverberg, 1998; Buisson and Bertrand,
      2001; Houlihan et al., 2001). High- and low-affinity alpha4beta2 nAChRs differ
      significantly in their functional and pharmacological properties (Zwart and
      Vijverberg, 1998; Buisson and Bertrand, 2001; Houlihan et al., 2001; Nelson et
      al., 2003) and result from the assembly of alpha4 and beta2 subunits into two
      distinct stoichiometric arrangements: (alpha4)2(beta2)3(high-affinity subtype)
      and (alpha4)3(beta2)2 (low-affinity subtype) (Nelson et al., 2003). In this study
      we have examined the functional and pharmacological properties of high- and low
      affinity alpha4beta2 receptors using two-electrode voltage clamp procedures on
      Xenopus oocytes transfected with high (1:10) or low (10:1) ratios of alpha4/beta2
      cDNAs, which yield high (1:10)- or low (10:1)- affinity receptors with monophasic
      ACh concentration- response curves. Furthermore, to determine the stoichiometry
      of high- and low-affinity receptors expressed heterologously by Xenopus oocytes,
      we have determined the stoichiometry of high- and low-affinity alpha4beta2
      receptors by mutating a highly conserved hydrophobic residue in the middle
      (position 9') of the pore-lining domain, which increases agonist potency in a
      manner that allows predictions on subunit composition (Cooper et al., 1991; Revah
      et al., 1991; Labarca et al., 1995; Boorman et al., 2000).

PMID- 17192645
TI  - Phosphorylation and function of alpha4beta2 receptor.
AB  - The neuronal nicotinic acetylcholine receptor (nAChR) alpha4 and beta2 subunits
      expressed in heterologous expression systems assemble into high- and low-affinity
      receptors (Zwart and Vijverberg, 1998; Buisson and Bertrand, 2001; Houlihan et
      al., 2001; Nelson et al., 2003), which reflects the assembly of two distinct
      subunit stoichiometries of alpha4beta2 receptor (Nelson et al., 2003). The high
      affinity receptor ([alpha4]2[beta2]3) is about 100-fold more sensitive to ACh
      than the low-affinity receptor ([alpha4]3[beta2]2) (Zwart and Vijverberg, 1998;
      Buisson and Bertrand, 2001; Houlihan et al., 2001; Nelson et al., 2003). Recent
      evidence implicated 14-3-3 proteins as modulators of the relative abundance of
      nAChR subunits in the endoplasmic reticulum (ER), where ligand-gated ion channels
      assemble. The 14-3-3 proteins influence ER-to-plasma membrane trafficking of
      multimeric cell-surface proteins (O'Kelly et al., 2002). 14-3-3 proteins bind
      components of these multimeric proteins, and this interaction overrides dibasic
      COP1 retention signal to permit forward transport of the protein (O'Kelly et al.,
      2002). In the case of alpha4beta2 nAChRs, 14-3-3 binds the alpha4 subunit, and
      this association is dependent on phosphorylation of a serine residue within a
      protein kinase A(PKA) consensus sequence in the large cytoplasmic domain of the
      alpha4 subunit, which is also a binding motif recognized by 14-3-3 (Jeancloss et
      al., 2001; O'Kelly et al., 2002). The interplay among PKA, alpha4 subunits, and
      14-3-3 proteins increases cell-surface expression of alpha4beta2 nAChRs by
      increasing steady-state levels of the alpha4 subunit available for assembly with
      beta2 subunits (Jeancloss et al., 2001). Because it is not known how 14-3-3
      dependent changes in the steady-state levels of the alpha4 subunit might affect
      the functional type of alpha4beta2 receptors, we have investigated the effects of
      mutations of the 14-3-3 binding motif in the alpha4 subunit on alpha4beta2 nAChR
      function.

PMID- 17192646
TI  - Remodeling of the neuromuscular junction in mice with deleted exons 5 and 6 of
      acetylcholinesterase.
AB  - At the vertebrate skeletal neuromuscular junction (NMJ), two closely related
      enzymes can hydrolyze acetylcholine (ACh): acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE). Advances in mouse genomics offer new approaches to
      assess the role of specific cholinesterases involved in neuromuscular
      transmission (Minic et al., 2003). AChE knockout mice provide a valuable tool for
      examining the effects of long-term complete and selective abolition of AChE
      activity (Xie et al., 2000). AChE and BChE genes encode two functional domains-
      the catalytic domain (exons 2, 3, and 4 of AChE, or exon 2 of BChE) and a C
      terminal domain (exon 5 or 6 of AChE, or exon 3 of BChE)--that dictate the
      targeting of the enzymes (Massoulie, 2002). In mammals, the AChE gene produces
      three types of coding regions by deleting 5'- splice acceptor sites, which
      generate proteins; these proteins possess the same catalytic domain associated
      with distinct C-terminal peptides. AChE subunits of type R (readthrough) produce
      soluble monomers; they are expressed during development and are thought to be
      induced in the mouse brain by stress (Kaufer et al., 1998). AChE subunits of type
      H (hydrophobic) produce GPI-anchored dimers, mainly in blood cells. Subunits of
      type T (tailed) exist for both AChE and BChE. They represent the predominant AChE
      variant expressed in cholinergically innervated tissues (muscle and nerve). These
      subunits generate a variety of quaternary structures, including homomeric
      oligomers (monomers, dimers, tetramers), as well as hetero-oligomeric assemblies
      with anchoring proteins ColQ (Krejci et al., 1997) and PRiMA (Perrier et al.,
      2002). At the NMJ, AChE is clustered by the interaction of the coding sequence of
      exon 6 with ColQ (Feng et al., 1999). The deletion of exons 5 and 6 in the AChE
      gene transforms anchored AChE into a soluble enzyme (Camp et al., 2004). The
      present study was designed to evaluate neuromuscular transmission and nicotinic
      ACh receptor (nAChR) distribution in muscles from mutant mice with deletions of
      these two spliced exons (AChE-del-exons-5+6-/-).

PMID- 17192647
TI  - Structural characterization of agonist and antagonist-bound acetylcholine-binding
      protein from Aplysia californica.
AB  - Nicotinic acetylcholine receptors (nAChRs) are well-characterized allosteric
      transmembrane proteins involved in the rapid gating of ions elicited by ACh.
      These receptors belong to the Cys-loop superfamily of ligand-gated ion channels,
      which also includes GABAA and GABAC, 5-HT3, and glycine receptors. The nAChRs are
      homo- or heteromeric pentamers of structurally related subunits that encompass an
      extracellular N-terminal ligand-binding domain, four transmembrane-spanning
      regions that form the ion channel, and an extended intracellular region between
      spans 3 and 4. Ligand binding triggers conformational changes that are
      transmitted to the transmembrane-spanning region, leading to gating and changes
      in membrane potential. The four transmembrane spans on each of the five subunits
      create a substantial region of hydrophobicity that precludes facile
      crystallization of this protein. However the freshwater snail, Lymnaea stagnalis,
      produces a soluble homopentameric protein, termed the ACh-binding protein
      (AChBP), which binds ACh (Smit et al., 2001). Its structure was determined
      recently (Brejc et al., 2001) at high resolution, revealing the structural
      scaffold for nAChR, and has become a functional and structural surrogate of the
      nAChR ligand-binding domain. We have characterized an AChBP from Aplysia
      californica and determined distinct ligand-binding properties when compared to
      those of L. stagnalis, including ligand specificity for the nAChR alpha7 subtype
      specific alpha-conotoxin ImI (Hansen et al., 2004).

PMID- 17192648
TI  - Structural comparison of three crystalline complexes of a peptidic toxin with a
      synaptic acetylcholine recognition protein.
AB  - Many peptidic toxins from animal venoms target neuronal or peripheral synaptic
      receptors with high affinities and specificities. Hence, these toxins are not
      only potent natural weapons but also precise molecular tools for pharmacological
      studies of their receptors. Although they belong to various structural and/or
      functional subfamilies, they often share similar molecular features, such as a
      highly reticulated scaffold presenting specific binding determinants.

PMID- 17192649
TI  - Targeted in vivo expression of nicotinic acetylcholine receptors in mouse brain
      using lentiviral expression vectors.
AB  - Nicotinic acetylcholine receptors (nAChRs) in the brain exhibit diverse
      functional properties and ubiquitous distribution. Yet, except for providing a
      receptor for the exogenously applied nicotine of tobacco products, their role in
      the normal functioning of the brain has remained elusive. We have used a
      lentiviral expression vector to re-express the beta2 subunit specifically in the
      ventral tegmental area (VTA) of beta2-/- mice. The viral vector efficiently
      expresses beta2- subunit protein leading to new nAChR-binding sites. VTA neurons
      transduced by the lentiviral vector are responsive to intravenous nicotine when
      analyzed using in vivo electrophysiology. Nicotine-induced dopamine release from
      the nucleus accumbens (NuAcc) was also restored in re-expressing beta2-/- mice.
      Intra-VTA injection of nicotine was found to be reinforcing in both wild-type and
      beta2-subunit re-expressing beta2-/- mice, but not in beta2-/- mice. Furthermore,
      in the absence of applied nicotine, the spontaneous slow exploratory behavior of
      the mice was restored, whereas fast navigation did not change. This latter
      behavioral analysis suggests a role for beta2* nAChR, specifically expressed in
      the VTA, in mammalian cognitive function.

PMID- 17192650
TI  - Expression of nicotinic acetylcholine receptors on murine alveolar macrophages.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) play an essential role in
      immunomodulation of macrophages. In particular, the alpha7 subunit confers
      inhibition of the systemic inflammatory response to bacterial lipopolysaccharide,
      thereby being the crucial element of the cholinergic anti-inflammatory pathway
      (Borovikova et al., 2000; Pavlov et al., 2003; Wang et al., 2003). In the murine
      lung, nicotine also exerts anti-inflammatory effects (Blanchet et al., 2004), but
      at least in murine alveolar macrophage cell lines the alpha7 subunit has not been
      detected (Matsunaga et al., 2001). On this background we investigated the
      expression of the nAChR subunits (alpha2-alpha7, alpha9, alpha10, beta2-beta4) on
      freshly isolated murine alveolar macrophages by immunohistochemistry and RT-PCR.

PMID- 17192651
TI  - Desensitization characteristics of the human alpha7nAChR/5HT3A chimera receptor.
AB  - The alpha7-nicotinic acetylcholine receptor (alpha7) is an important ionotropic
      receptor in the central nervous system, which becomes permeable to cations upon
      binding of its natural agonist acetylcholine (ACh). alpha7 kinetics are
      characterized by rapid activation, followed by fast desensitization of the
      current. As the wild-type (WT) alpha7 is difficult to express heterologously in
      mammalian cellular systems, frequently a more easily expressible chimera
      consisting of the extracellular domain of the alpha7 and the transmembrane domain
      of the 5HT3A receptor is used to study alpha7 pharmacology (chick alpha7/mouse
      5HT3A [Eisele et al., 1993]; human alpha7/mouse 5HT3A [Graig et al., 2004]).
      Desensitization characteristics of these chimera receptors have been described as
      intermediate compared with the fast desensitizing alpha7 and the more slowly
      desensitizing 5HT3A receptors. Here, we describe a fully human chimera receptor
      (h-alpha7/5HT3A), which is characterized by desensitization, and recovery
      kinetics that deviate from the human WT alpha7.

PMID- 17192653
TI  - Interaction of pyridinium oximes with acetylcholinesterase and their effect on
      organophosphate-poisoned mice.
AB  - The progressive inhibition of acetylcholinesterase (AChE [EC 3.1.1.7]) by
      organophosphates (OPs), such as the nerve agents tabun and soman, is due to
      phosphorylation of the active center serine characterized by the formation of
      conjugates and inactivation of this essential enzyme involved in
      neurotransmission. Presently, a combination of an antimuscarinic agent, e.g.,
      atropine, and an AChE reactivator, oxime, is used for the treatment of
      organophosphorus compound poisoning. The increased concern about terrorist use of
      nerve agents prompted us to search for new, more effective oximes against tabun
      and soman poisoning. We investigated the interactions of five bispyridinium
      oximes with human erythrocyte AChE and their effects on tabun- and soman-poisoned
      mice.

PMID- 17192652
TI  - Determinants of positive cooperativity between strychnine-like allosteric
      modulators and N-methylscopolamine at muscarinic receptors.
AB  - It has been shown previously that the third extracellular loop (o3) and its
      vicinity play a critical role in allosteric modulation at muscarinic
      acetylcholine receptors (mAChRs) (Ellis et al., 1993; Krejci and Tucek, 2001;
      Buller et al., 2002). In this study interaction of four chemically related
      substances (strychnine, its dimethoxy derivate brucine, precursor for synthesis
      of strychnine Wieland-Gumlich aldehyde (WGA), and precursor for synthesis of
      alcuronium propargyl-WGA) with orthosteric antagonist N-methylscopolamine (NMS)
      was investigated on the M3 subtype of mAChRs mutated at the o3 loop.

PMID- 17192654
TI  - The role of the cytoskeleton in neuromuscular junction formation.
AB  - The cytoskeleton plays a vital role in neuromuscular junction (NMJ) formation. It
      is responsible for shaping synaptic membrane into folds opposed to presynaptic
      active zones and anchoring acetylcholine receptors (AChRs) to the crest of the
      junctional folds. Acetylcholine receptors (AChRs) associate with the actin
      cytoskeleton, the disruption of which affects spontaneous and agrin-induced AChR
      clusters (Prives et al., 1982; Connolly, 1984; Peng and Phelan, 1984; Bloch,
      1986; Dai et al., 2000). How AChRs are tethered to the actin cytoskeleton remains
      unclear.

PMID- 17192655
TI  - Ethanol consumption produces changes in behavior and on hippocampal alpha7 and
      alpha4beta2 nicotinic receptors.
AB  - Ethanol consumption produces a wide range of effects on the central nervous
      system, most of them related to changes in neural receptors. In vitro studies
      have demonstrated that ethanol increases neural nicotinic acetylcholine receptor
      (nnAChR) affinity for ACh (Narahashi et al., 1991) and have also reported
      differences in sensitivity of nnAChRs for ethanol, depending on the subunit
      composition of the receptor (Cardoso et al., 1999). There is evidence that
      ethanol induces changes in density of nnAChRs in cellular cultures (Gorbounova et
      al., 1998). However, there are no clear results concerning the effects of chronic
      ethanol on nicotinic receptors and on behavior in rats nonselected by their
      preference to ethanol. A number of studies demonstrate that nnAChRs participate
      in a variety of functions, including memory and learning processes,
      neurodegeneration, and neuroprotection (Picciotto et al., 2000). In the present
      work, we found significant alterations in the Fixed-Interval Behavioral Test, as
      well as in density and affinity parameters of hippocampal main subtypes of
      nnAChRs: alpha7 homopentamers and alpha4beta2 heteropentamers of ethanol-drinking
      rats nonselected by their preference to ethanol.

PMID- 17192656
TI  - Structural and functional changes induced in the nicotinic acetylcholine receptor
      by membrane phospholipids.
AB  - Ligand-gated ion channels (LGICs) constitute an important family of complex
      membrane proteins acting as receptors for neurotransmitters (Barnard, 1992;
      Ortells and Lunt, 1995). The nicotinic acetylcholine receptor (nAChR) from
      Torpedo is the most extensively studied member of the LGIC family and consists of
      a pentameric transmembrane glycoprotein composed of four different polypeptide
      subunits (alpha, beta, gamma, and delta) in a 2:1:1:1 stoichiometry (Galzi and
      Changeux, 1995; Hucho et al., 1996) that are arranged pseudosymmetrically around
      a central cation-selective ion channel. Conformational transitions, from the
      closed (nonconducting), to agonist-induced open (ion-conducting), to desensitized
      (nonconducting) states, are critical for functioning of the nAChR (Karlin, 2002).
      The ability of the nAChR to undergo these transitions is profoundly influenced by
      the lipid composition of the bilayer (Barrantes, 2004). Despite existing
      information on lipid dependence of AChR function, no satisfactory explanation has
      been given on the molecular events by which specific lipids exert such effects on
      the activity of an integral membrane protein. To date, several hypotheses have
      been entertained, including (1) indirect effects of lipids through the alteration
      of properties of the bilayer, such as fluidity (an optimal fluidity hypothesis
      [Fong and McNamee, 1986]) or membrane curvature and lateral pressure (Cantor,
      1997; de Kruijff, 1997), or (2) direct effects through binding of lipids to
      defined sites on the transmembrane portion of the protein (Jones and McNamee,
      1988; Blanton and Wang, 1990; Fernandez et al., 1993; Fernandez-Ballester et al.,
      1994), which has led to the postulation of a possible role of certain lipids as
      peculiar allosteric ligands of the protein. In this paper we have reconstituted
      purified AChRs from Torpedo into complex multicomponent lipid vesicles in which
      the phospholipid composition has been systematically altered. Stopped-flow rapid
      kinetics of cation translocation and Fourier transform-infrared (FT-IR)
      spectroscopy studies have been used to illustrate the lipid dependence of both
      AChR function and AChR secondary structure, respectively.

PMID- 17192657
TI  - A cholinergic mechanism for eye fixation.
AB  - A basic question regarding the integrative properties of the central nervous
      system is how transient motor commands or brief sensory stimuli are able to evoke
      persistent neural changes, mainly in the form of a sustained tonic rate of action
      potentials. Examples of this persistent neural activity have been reported in
      prefrontal (Fuster, 1997) and entorhinal (Egorov et al., 2002) cortices, as part
      of the neural mechanisms involved in short-term working memory (Goldman-Rakic,
      1995). Interestingly enough, the general organization of motor systems assumes
      the presence of bursts of short-lasting motor commands encoding movement
      characteristics such as velocity, duration, and amplitude, followed by a
      maintained tonic firing encoding the position at which the moving appendage
      should be maintained (Robinson, 1981; Moschovakis, 1997). Thus, persistent neural
      activity seems to be necessary for both behavioral (positions of fixation) and
      cognitive (working memory) processes.

PMID- 17192658
TI  - Toxicodynamic modeling of highly toxic organophosphorus compounds.
AB  - Although the in vitro effect of organophosphorus (OP) compounds on acetylcholine
      esterase (AChE) has been studied extensively, the hypothesis that OP inhibition
      of AChE is the primary mechanism of acute in vivo OP toxicity has been
      controversial. For example, a recent review (Pope and Liu, 2004) suggested that
      OP compounds have direct toxic effects on other enzymes, ACh receptors, and
      receptor/ channel complexes that are independent of AChE inhibition. The purpose
      of this report is to examine the hypothesis that AChE inhibition is the mechanism
      of acute toxicity of OP compounds by mathematically modeling the in vivo lethal
      effects of highly toxic OP compounds and determining the amount of variation in
      OP toxicity that is explained by AChE inhibition.

PMID- 17192659
TI  - Cholinergic modulation of cortical function.
AB  - Extensive physiological research has demonstrated a number of common effects of
      acetylcholine within cortical structures, including the hippocampus, piriform
      cortex, and neocortex (Hasselmo, 1995, 1999). This article will provide a
      description of how the different physiological effects of acetylcholine could
      interact to alter specific functional properties of the cortex. The physiological
      effects of acetylcholine serve to enhance the influence of feed- forward afferent
      input to the cortex while decreasing background activity by suppressing
      excitatory feedback connections within cortical circuits. By enhancing the
      response to sensory input, high levels of acetylcholine enhance attention to
      sensory stimuli in the environment and enhance encoding of memory for specific
      stimuli. Interference from prior memory is reduced by suppressing synapses
      modified by prior learning (Sevilla et al., 2002; Linster et al., 2003).

PMID- 17192660
TI  - Nicotinic receptors modulate transmitter cross talk in the CNS: nicotinic
      modulation of transmitters.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) in the CNS appear to exert a
      predominantly modulatory influence on brain mechanisms, despite being fast-acting
      ligand-gated ion channels. Many nAChRs have an extrasynaptic location on
      somatodendritic regions or presynaptic terminals. They influence local
      excitability by depolarization and can initiate short- and long-term changes by
      interfacing with Ca2+ signaling pathways (Dajas- Bailador and Wonnacott, 2004).
      The modulation of neurotransmitter release by presynaptic nAChRs is well
      documented (Wonnacott, 1997): Both Na+ and Ca2+ fluxes associated with nAChR
      activation can influence transmitter release. It is also emerging that nAChRs,
      especially the alpha7 subtype, can exert an indirect effect on transmitter
      release, through modulation of amino acid transmitters. This complex scenario
      facilitates transmitter cross talk, which is the subject of this short review.

PMID- 17192661
TI  - Can cholinesterase inhibitors provide additional effects to cholinergic
      neurotransmission enhancement?
AB  - The most frequent of the primary degenerative dementias is Alzheimer's disease
      (AD). The gradual loss of memory and attention in patients suffering from this
      illness are accompanied by aphasia, apraxia, agnosia, and alterations in visual
      spatial perception. This group of symptoms is completed by emotional alterations,
      psychic instability, and changes in personality that appear in advanced phases of
      the illness. Different histopathological alterations have been described, like
      marked atrophy of the cerebral cortex with loss of cortical and subcortical
      neurons. Other histopathological hallmarks are the formation of senile plaques
      composed of beta-amyloid (Abeta) and neuro fibrillary tangles composed of
      hyperphosphorylation of tau protein.

PMID- 17192662
TI  - Bioscavenger for protection from toxicity of organophosphorus compounds.
AB  - Current antidotal regimens for organophosphorus compound (OP) poisoning consist
      of a combination of pretreatment with a spontaneously reactivating AChE inhibitor
      such as pyridostigmine bromide, and postexposure therapy with anticholinergic
      drugs such as atropine sulfate and oximes such as 2-PAM chloride (Gray, 1984).
      Although these antidotal regimens are effective in preventing lethality of
      animals from OP poisoning, they do not prevent postexposure incapacitation,
      convulsions, performance deficits, or, in many cases, permanent brain damage
      (Dunn and Sidell, 1989). These problems stimulated the development of enzyme
      bioscavengers as a pretreatment to sequester highly toxic OPs before they reach
      their physiological targets. Several studies over the last two decades have
      demonstrated that exogenously administered human serum butyrylcholinesterase (Hu
      BChE) can be used successfully as a safe, efficacious, and single prophylactic
      treatment to counteract the toxicity of OPs. It also has potential use for first
      responders (civilians) reacting to terrorist nerve gas release, pesticide
      overexposure, or succinylcholine-induced apnea. A dose of 200 mg of Hu BChE in
      humans is envisioned as a prophylactic treatment that can protect from exposure
      of 2-5 x LD50 of nerve agents (Ashani, 2000).

PMID- 17192663
TI  - Nicotinic signal transduction machinery.
AB  - Nicotinic synapses employ acetylcholine to activate ligand-gated ion channels
      that are cation-selective in vertebrates. Although the resulting nicotinic
      cholinergic transmission is famously excitatory at the neuromuscular junction, it
      plays many additional roles in the CNS. Most prevalent is that of modulation,
      usually involving calcium and signal transduction. Because of this, it is
      becoming increasingly important not only to understand the mechanisms that guide
      nicotinic receptors to appropriate locations but also to identify the
      postsynaptic machinery making possible the requisite signal transduction.
      Clearly, the kinds of components tethered in the vicinity of the receptor will
      assume a major role in determining the consequences of receptor activation. One
      of the most abundant and interesting nicotinic receptors in this respect is the
      species comprised of the alpha7 gene product (Broide and Leslie, 1999). These
      alpha7 homopentameric nicotinic acetylcholine receptors (alpha7 nAChRs) have a
      high relative permeability to calcium, rivaling that of NMDA receptors. But
      unlike NMDA receptors, alpha7 nAChRs promote calcium influx without requiring a
      coincident event such as membrane depolarization. As a result, the receptors are
      well equipped to regulate calcium-dependent events in neurons, particularly when
      depolarization might be occluded.

PMID- 17192664
TI  - Role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine
      receptors.
AB  - Neurotransmitter-gated receptors are assembled in the endoplasmic reticulum and
      transported to the cell surface through a process that might be of central
      importance to regulate the efficacy of synaptic transmission (Kneussel and Betz,
      2000; Kittler and Moss, 2003). This process is relatively inefficient- what may
      be the consequence of tight quality controls that guarantee the functional
      competence of the final product. For this purpose, specific proteins involved in
      assembly and trafficking of receptors might be required (Keller and Taylor, 1999;
      Millar, 2003; Wanamaker et al., 2003). The RIC-3 protein could be one of them, as
      mutations in the ric-3 gene affect maturation of nicotinic acetylcholine
      receptors (nAChRs) in Caenorhabditis elegans (Halevi et al., 2002). Moreover, the
      human homolog hRIC-3 showed differential effects when coexpressed with several
      ligand-gated receptors (Halevi et al., 2003). Thus, it enhanced alpha7 nAChR
      expression while inhibiting expression of other nAChR subtypes (alpha4beta2 and
      alpha3beta4) and 5-HT3 serotonin receptors (5-HT3Rs). These opposite effects
      suggested that the RIC-3 protein might play a key role in the biogenesis of some
      ligand-gated receptors and prompted us to investigate how it performs its action.
      Here, we show that the RIC-3 protein acts as a barrier for some receptors like
      alpha4beta2 nAChRs and 5-HT3Rs, stopping the traffic of mature receptors to the
      membrane. In contrast, the inefficient transport of alpha7 nAChRs is enhanced by
      RIC-3 in a process in which certain amino acids at the amphipathic helix located
      at the C-terminal region of the large cytoplasmic domain are involved.

PMID- 17192665
TI  - M1-M3 muscarinic acetylcholine receptor-deficient mice: novel phenotypes.
AB  - The five muscarinic acetylcholine receptors (M1-M5 mAChRs) mediate a very large
      number of important physiological functions (Caulfield, 1993; Caulfield and
      Birdsall, 1998; Wess, 2004). Because of the lack of small molecule ligands
      endowed with a high degree of receptor subtype selectivity and the fact that most
      tissues or cell types express two or more mAChR subtypes, identification of the
      physiological and pathophysiological roles of the individual mAChR subtypes has
      proved to be a challenging task. To overcome these difficulties, we recently
      generated mutant mouse lines deficient in each of the five mAChR genes (M1R-/-
      mice, M2R-/- mice, M3R-/- mice, etc. [Wess, 2004]). Phenotyping studies showed
      that each of the five mutant mouse lines displayed characteristic physiological,
      pharmacological, behavioral, biochemical, or neurochemical deficits (Wess, 2004).
      This chapter summarizes recent findings dealing with the importance of the
      M2mAChR for cognitive processes and the roles of the M1 and M3 mAChRs in
      mediating stimulation of glandular secretion.

PMID- 17192666
TI  - Presynaptic muscarinic control of glutamatergic synaptic transmission.
AB  - The hippocampus receives cholinergic projections from the medial septal nucleus
      and Broca's diagonal band that terminate in the CA1, CA3, and dentate gyrus
      regions (Frotscher and Leranth, 1985). Glutamatergic synapses between CA3 and CA1
      pyramidal neurons are presynaptically inhibited by acetylcholine (ACh), via
      activation of muscarinic ACh receptors (mAChRs) at the terminals of Schaffer
      collaterals (SCs) (Hounsgaard, 1978; Fernandez de Sevilla et al., 2002, 2003).
      There are two types of SC-CA1 pyramidal neuron synapses. One type, called
      functional synapse, shows postsynaptic alpha- amino-3-hydroxy-5-methyl-4
      isoxazole propionate (AMPA)-receptor mediated currents at resting potential (Vm)
      and both AMPA and N-methyl-D-aspartate receptor (NMDAR)-mediated currents when
      depolarized. The other type, termed silent synapse, only displays postsynaptic
      NMDAR-mediated currents at depolarized Vms, but does not respond at the resting
      Vm (Isaac et al., 1995). Using hippocampal slices obtained from young Wistar
      rats, we examined the effects of activation of cholinergic afferents at the
      stratum oriens/alveus on excitatory postsynaptic currents (EPSCs) evoked in CA1
      pyramidal neurons by stimulation of SCs. We also tested the action of the
      nonhydrolyzable cholinergic agonist carbamylcholine chloride (CCh) on EPSCs
      evoked by minimal stimulation of SCs (which activates a single or very few
      synapses) in functional and silent synapses.

PMID- 17192667
TI  - Allosteric modulators and selective agonists of muscarinic receptors.
AB  - Allosteric modulators of ligand-receptor interactions are found for a variety of
      receptors (Christopoulos, 2002). Allosteric agents attach to a binding site being
      topographically distinct from the site for conventional (orthosteric) agonists or
      antagonists. In the case of the muscarinic receptor, a huge selection of
      structurally divergent modulators has been described for different receptor
      subtypes (Mohr et al., 2003). Alkane-bisammonio-type compounds carrying lateral
      phthalimido substituents are known to have a high affinity for the common
      allosteric binding site of the muscarinic acetylcholine M2 receptor (mAChR M2),
      which is already occupied by the orthosteric antagonist N-methylscopolamine
      (NMS). The resulting allosteric inhibition of the dissociation of [3H]NMS from
      the M2 receptors in porcine cardiac homogenates served to indicate binding of the
      test compounds to the allosteric site. Additionally, allosteric modulators can
      strongly influence equilibrium binding of the orthosteric ligand: Its binding can
      be reduced, left unaltered or elevated, and encoded as negative, neutral, and
      positive cooperativity, respectively (Christopoulos and Kenakin, 2002). The
      cooperativity is strongly dependent on the pair of allosteric/orthosteric ligands
      and on the receptor subtype.

PMID- 17192668
TI  - Cognitive enhancement in man with ispronicline, a nicotinic partial agonist.
AB  - Cholinergic mechanisms are clearly involved in memory deficits associated with
      Alzheimer's disease (AD) (Perry et al., 1977). Recently, there has been growing
      interest in the nicotinic approach to the treatment of AD; however, compounds
      have failed in the clinic because of a lack of separation between central and
      peripheral nicotinic effects (Potter et al., 1999). Ispronicline (TC-1734) is an
      orally active, selective, partial agonist of the central alpha4beta2 neuronal
      nicotinic acetylcholine receptor (nAChR), with high binding affinity to membrane
      preparations from rat brain or mammalian cells expressing recombinant human
      alpha4beta2 receptor (Gatto et al., 2004). Ispronicline has no detectable effects
      on muscle or ganglionic nAChRs, indicating a marked CNS over PNS selectivity. In
      animal models ispronicline potently improved cognitive function. A long duration
      of memory enhancement was displayed in object recognition and radial arm maze
      tests. Ispronicline pharmacokinetics (half-life of 2 h in rats) contrasts with
      the long-lasting improvement of working memory (18 h to 2 d) (Gatto et al.,
      2004).

PMID- 17192669
TI  - Interaction between P2X and nicotinic acetylcholine receptors in glutamate nerve
      terminals of the rat hippocampus.
AB  - Nicotinic acetylcholine receptors (nAChRs [constituted by pentameric association
      of alpha2-10 and beta2-4 subunits]) and P2X receptors (P2XRs [activated by ATP
      and constituted by multimeric association of P2X1-7 subunits]) are both
      ionotropic receptors permeable to cations, which have in common the disparity
      between the wealth of data showing their presence in the brain and little
      evidence of their participation in mediating synaptic transmission. This has led
      to the proposal that both nAChRs and P2XRs might primarily modulate rather than
      directly mediate synaptic transmission, which is in accordance with the
      predominant presynaptic localization of both receptor subtypes (Role and Berg,
      1996; Cunha and Ribeiro, 2000). Interestingly, both functional neurochemical
      (Allgaier et al., 1995; Salgado et al., 2000; Diaz-Hernandez et al., 2002) and
      electrophysiological studies (Barajas-Lopez et al., 1998; Searl et al., 1998;
      Zhou and Calligan, 1998; Khakh et al., 2000) indicated a close interaction
      between nAChRs and P2XRs, which is paralleled by a co-release of ATPand ACh from
      central terminals (e.g., Richardson and Brown, 1987). Because glutamate release
      in the hippocampus is controlled by both nAChRs (e.g., McGehee et al., 1995) and
      P2XRs (Khakh et al., 2003; Rodrigues et al., 2005), we investigated if there was
      a functional interaction between these two presynaptic ionotropic receptors in
      the control of glutamate release in the rat hippocampus.

PMID- 17192670
TI  - Role of CaCMKII in the cross talk between ionotropic nucleotide and nicotinic
      receptors in individual cholinergic terminals.
AB  - Ionotropic P2X receptors for ATP are formed, to date, by seven different subunits
      named P2X (Torres et al., 1999; Cunha and Ribeiro, 2000; North and Surprenant,
      2000; Pintor et al., 2000; Hervas et al., 2003; Miras-Portugal et al., 2003;
      Illes and Ribeiro, 2004), which are cloned from various mammalian species (Illes
      and Ribeiro, 2004). These subunits can occur as homo- or hetero-oligomeric
      assemblies of more than one subunit (North and Surprenant, 2000), except P2X
      (Miras-Portugal et al., 2003) receptor, which has been described not to
      coassemble with other subunits (Torres et al., 1999). They are abundantly
      expressed in the peripheral and central nervous systems and exhibit high
      permeability to Ca2+ ions (Cunha and Ribeiro, 2000). The existence of presynaptic
      ionotropic receptors for nucleotides, either for ATP or dinucleotides, has been
      reported in isolated synaptic terminals from mammalian brain, and both exhibit
      good permeability to Ca2+ ions (Pintor et al., 2000; Hervas et al., 2003; Miras
      Portugal et al., 2003). Studies on isolated single terminals have confirmed the
      existence of independent and specific responses to ATP and dinucleotides on the
      same or different terminals (Miras-Portugal et al., 1999; Diaz-Hernandez et al.,
      2002; Hervas et al., 2005; Sanchez-Nogueiro et al., 2005). The activation of
      presynaptic ionotropic nucleotide receptors can induce the release of other
      neurotransmitters such as acetylcholine, glutamate, or GABA. In these specific
      terminals, ionotropic nucleotide receptors can be modulated by interaction with
      metabotropic receptors, such as GABAB and adenosine receptors (Khakh and
      Henderson, 1998; Gomez-Villafuertes et al., 2001), and ionotropic, such as
      nicotinic cholinergic receptors (Diaz-Hernandez et al., 2004; Sanchez-Nogueiro et
      al., 2005). Here, we discuss a relevant finding on the interaction between
      ionotropic nucleotide and nicotinic receptors in cholinergic synaptic terminals
      and the role of CaCMKII in this interaction.

PMID- 17192672
TI  - Effect of acetylcholine on tau phosphorylation in human neuroblastoma cells.
AB  - Alzheimer's disease (AD) is a senile dementia characterized by a progressive loss
      of memory, together with cognitive and behavioral impairments. In the past it was
      indicated that the disease was associated with a loss of acetylcholine (ACh) in
      the cerebral cortex (Bowen et al., 1976; Davies and Maloney, 1976); afterward, it
      was indicated that the severity of dementia was correlated with the extent of
      cholinergic loss (Perry et al., 1981). Because one of the biochemical features of
      AD is modification by phosphorylation of the microtubule-associated protein tau
      (for review, see Avila et al., 2004), in this work we indicate the effect of ACh
      on tau phosphorylation at specific sites recognized by 12E8 and PThr50 antibodies
      in human neuroblastoma SH-SY5Y cells. Two sites in which modification might
      regulate the binding of tau to microtubules (Novak et al., 1991; Feijoo et al.,
      2004).

PMID- 17192671
TI  - CNS localization of neuronal nicotinic receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop
      superfamily of pentameric ligand-gated ion channels, which include GABA (A and
      C), serotonin, and glycine receptors. Currently, 12 neuronal nAChR subunits have
      been identified (alpha2-10 and beta2-4) and are generally grouped into alpha
      subunits, which contain two adjacent cysteine residues essential for ACh binding,
      and beta subunits, which lack these residues. The majority of neuronal nAChRs
      fall into two categories: those that bind agonist with high affinity (nM
      concentrations); and those that bind with lower affinity (microM concentrations).
      The low-affinity receptors are presumably homomeric alpha7 receptors that are
      alpha-bungarotoxin sensitive, whereas alpha4beta2 nAChRs account for >90% of the
      high-affinity nicotinic receptors in the brain (Whiting and Lindstrom, 1986).
      Their physiological contributions to neurotransmission, signaling, and behavior
      are not completely understood. Precise mapping of subcellular and neuroanatomical
      localizations of neuronal nAChR subunits will help elucidate the physiological
      role of neuronal nAChRs and their role in nicotine addiction.

PMID- 17192673
TI  - Transcriptional control of different acetylcholinesterase subunits in formation
      and maintenance of vertebrate neuromuscular junctions.
AB  - Acetylcholinesterase (AChE; EC 3.1.1.7) is a highly polymorphic enzyme
      (Massoulie, 2002). Asingle ACHE gene produces several types of catalytic subunits
      by alternative splicing, but a single splice variant, called type T (AChET), is
      expressed in adult mammalian muscle and brain. Catalytic subunits of AChET
      produce amphiphilic monomers and dimers, nonamphiphilic homotetramers, as well as
      heteromeric associations with anchoring proteins, ColQ (collagenous subunit) and
      PRiMA (proline-rich membrane anchor), which allow their functional localization
      in cholinergic synapses (Massoulie, 2002). ColQ characterizes the collagen-tailed
      forms (Aforms) of AChE and butyrylcholinesterase (BChE), which are localized in
      the basal lamina at neuromuscular junctions (NMJs) of vertebrates (Krejci et al.,
      1999); in these molecules (A4, A8, A12), one, two, or three tetramers of
      catalytic subunits are disulfide-linked to the strands of a triple helix of ColQ
      collagen. The cDNAs encoding ColQ, which have two transcripts, have been cloned:
      ColQ-1a predominantly in fast-twitch muscle, and ColQ-1 predominantly in slow
      twitch muscle. The tetrameric globular (G4) form of AChE is characterized by
      linkage to PRiMA. PRiMAcDNA encodes a single-pass approximately 20-kDa type-I
      transmembrane protein and, similar to that of ColQ, contains a short PRAD
      (proline-rich attachment domain) that is able to organize AChE catalytic subunits
      into tetramers and anchor the enzyme at the surface of neuron and muscle
      (Massoulie, 2002).

PMID- 17192674
TI  - Production of the butyrylcholinesterase knockout mouse.
AB  - The butyrylcholinesterase (BChE [EC 3.1.1.8]) knockout mouse is a model for BChE
      deficiency in humans. The existence of genetic variants of human BChE was
      discovered after a new muscle relaxant, succinylcholine, was introduced into the
      practice of medicine in the late 1950s. People with the atypical variant were
      unable to breathe for 2 h after receiving a dose intended to paralyze for 3-5 min
      (Kalow and Gunn, 1957, 1959). The atypical variant was later found to have a
      single-amino-acid mutation at Asp-70 (McGuire et al., 1989), which decreased the
      affinity of BChE for all positively charged compounds. Though the atypical BChE
      mutant is the one most commonly encountered in cases of succinylcholine apnea, an
      additional 58 mutations in the BChE coding sequence have been reported. The
      frequency of BChE mutations in the American population is known (Lockridge,
      1990). One person out of 25 carries one atypical allele (D70G), whereas 1 out of
      2500 is homozygous for D70G. The most frequent mutation, A539T, is carried by 1
      person out of every 4 and is found in homozygous form in 1 person out of 69
      (Bartels et al., 1992). The homozygous A539T form is associated with a 33%
      decrease in plasma BChE activity. Some people have no detectable BChE activity in
      plasma, owing to a mutation that truncates the protein, or inactivates it. The
      frequency of silent BChE is 1 out of 160 for carriers, and 1 out of 110,000 for
      homozygotes. The BChE knockout mice are models for silent BChE in humans. The
      literature contains no documentation of the health of people with silent BChE,
      other than to say they are healthy. We know nothing about their life expectancy,
      fertility, risk of cognitive impairment, risk of heart disease, or susceptibility
      to toxins. The BChE knockout mouse will allow us to test the hypothesis that the
      function of BChE is to detoxify poisons and will allow us to test the role of
      BChE in other physiological functions.

PMID- 17192676
TI  - On functions of cholinesterases during embryonic development.
AB  - Expression of cholinesterase (ChE) activity during phases of embryonic
      development is a general phenomenon in embryonic tissues. To elucidate the
      role(s) of ChEs during embryonic development, one line of research followed the
      assumption of a primitive muscarinic system involved in morphogenesis (Hohmann et
      al., 1995). This means that ChE functioning during development fits into the
      classical cholinergic neurotransmitter system: acetylcholine (ACh), as a signal,
      binds to ACh receptors and then is degraded by acetylcholinesterase (AChE) as the
      terminating enzyme. However, this is just one of the possible mechanisms. The
      other line of research was driven by evidence for noncholinergic functions of ChE
      proteins (AChE and butyrylcholinesterase [BChE]). There is accumulating data that
      other sites on AChE could exert nonclassical roles related to cell
      differentiation, neurite outgrowth, and adhesion.

PMID- 17192675
TI  - Readthrough acetylcholinesterase: a multifaceted inducer of stress reactions.
AB  - Stress insults induce hyperexcitation of cholinergic circuits, both peripherally
      in the sympathetic pathway (Tracey, 2002) and at the central nervous system (CNS)
      (Sapolsky, 1996). This reaction can serve to ensure survival but might also
      entail a risk to the hyperactivated neurons. Consequent changes in the expression
      of a series of proteins related to acetylcholine (ACh) metabolism might protect
      the organism from the potentially detrimental effects of this increase in ACh. Of
      particular interest among these effects is the induction by alternative splicing
      of the alternative, usually rare, readthrough variant of acetylcholinesterase
      (AChE), AChE-R. AChE-R is one of the first proteins conveying the signal that the
      organism has entered a state of alert. Viewing AChER as a stress signal can
      therefore serve to answer the question "How do we expect a stress signal to
      operate"? This facilitates the generation of hypotheses regarding the triggering
      of such signals and the effects it exerts at the molecular, cellular, and
      physiological levels.

PMID- 17192678
TI  - Acetylcholine release in rapid synapses: two fast partners--mediatophore and
      vesicular Ca2+/H+ antiport.
AB  - Rapid neurotransmission is like lightning: a spark of calcium in the nerve
      terminal, a spark of transmitter in the cleft, and the signal is over. But "time
      is gained at the expense of sensitivity" (Katz, 1988); transmission relies on low
      affinity, high-speed reactions. These fast processes are modulated by regulating
      reactions that do not need to be so rapid.

PMID- 17192677
TI  - Quaternary ammonium anticholinesterases have different effects on nicotinic
      receptors: is there a single binding site?
AB  - Copious current research is devoted to finding new modulators of nicotine
      acetylcholine receptors (nAChRs), in view of their high relevance for nervous
      system physiology and because alterations in their number and/or function are
      related to several neurological disorders and neurodegenerative diseases (Pereira
      et al., 2002). Recently, we have shown that 1,5-bis(4-allyldimethyl ammonium
      phenyl) pentan-3-one dibromide (BW284c51), a quaternary ammonium cholinesterase
      inhibitor (QChEI), selectively inhibits nicotinic currents (IACh) by blocking the
      nAChR channel (Olivera et al., 2005). Interestingly, we found different effects
      of BW284c51 on nAChRs from those described previously for other QChEIs (Bertrand
      et al., 1992; Yost and Maestrone, 1994), such as decamethonium and edrophonium.
      Therefore, this work was aimed at characterizing, comparing, and elucidating the
      mechanisms underlying the action of different QChEIs on nAChRs.

PMID- 17192679
TI  - Modulation of calcium-dependent and -independent acetylcholine release from motor
      nerve endings.
AB  - Inhibition of acetylcholine (ACh) release by adenosine is an important mechanism
      by which the secretory apparatus is regulated at both mammalian (Ginsborg and
      Hirst, 1972; Hirsh et al., 2002; Silinsky, 2004) and amphibian (Silinsky, 1980;
      Silinsky and Solsona, 1992; Redman and Silinsky, 1993, 1994; Robitaille et al.,
      1999) neuromuscular junctions (NMJs). ACh is known to be costored with ATP in
      cholinergic vesicles (Zimmermann, 1994), and it has been demonstrated that at
      amphibian NMJs, adenosine derived from neurally released ATPis the mediator of
      neuromuscular depression exhibited at low frequencies of nerve stimulation
      (Redman and Silinsky, 1994) (Fig. 1). At the mouse motor nerve ending the
      inhibitory actions of adenosine on transmitter release are linked to a reduction
      in the nerve-terminal calcium current associated with neurotransmitter release
      (Silinsky, 2004). In contrast, at the frog motor nerve, inhibition of ACh release
      by adenosine occurs in the absence of any effect on nerve-terminal calcium
      currents (Silinsky and Solsona, 1992; Redman and Silinsky, 1994; Robitaille et
      al., 1999). That is, at the frog NMJ adenosine inhibits ACh release through an
      effect on a process that takes place downstream from calcium entry. Although the
      exact site at which adenosine inhibits transmitter release is unknown, both the
      speed (50-100 ms; E. M. Silinsky, unpublished observations) and the stimulation
      independent nature of inhibition suggest that this process must occur through an
      action on vesicles that are already primed and ready for release. Thus, the
      likely sites for mediating the action of adenosine are those core components of
      the neurotransmitter release process, the three SNARES (SNAP-25, syntaxin, and
      synaptobrevin), and synaptotagmin. However, there are difficulties in addressing
      which of these individual elements of the secretory apparatus might be involved
      in the actions of adenosine. We could use fractions of botulinum toxin to
      eliminate individual components of the secretory apparatus. However, each of
      these core components of the release machinery is individually essential for the
      neurotransmitter release process. Therefore, we decided to approach this problem
      by alternative means.

PMID- 17192680
TI  - Acetylcholine, cognition, and consciousness.
AB  - Acetylcholine (ACh) is a neuromodulator inextricably involved with higher mental
      functions. The organization of central pathways enables this role, as do the
      complex responses to ACh. This chapter focuses on intradendritic responses to
      ACh.

PMID- 17192681
TI  - MuSK signaling at the neuromuscular junction.
AB  - The neuromuscular junction (NMJ) is a peripheral cholinergic synapse that conveys
      signals from motor neurons to muscle cells (Sanes and Lichtman, 1999; Sanes and
      Lichtman, 2001). The formation of the NMJ requires communication between
      motoneurons and muscle fibers. Three molecules are essential for NMJ formation:
      agrin, MuSK, and rapsyn. MuSK appears to be involved in every aspect of NMJ
      development and maintenance. The paper reviews agrin-MuSK cascades and its
      potential cross talk with Wnt signaling pathways.

PMID- 17192683
TI  - The C-terminal T peptide of cholinesterases: structure, interactions, and
      influence on protein folding and secretion.
AB  - Mammalian cholinergic tissues mostly express the T splice variant of
      acetylcholinesterase, in which the catalytic domain is associated with a C
      terminal peptide of 40 residues, called the t peptide (Massoulie, 2002).
      Homologous t peptides exist in all vertebrate cholinesterases,
      acetylcholinesterases (AChEs), and butyrylcholinesterases (BChEs): they contain a
      series of seven conserved aromatic residues, including three tryptophans, and a
      cysteine at position-4 of their C-terminus. The major AChE isozyme of the
      nematode Caenorhabditis elegans also contains a similar peptide. Although the C
      terminal t peptides do not seem to affect the catalytic activity of
      cholinesterases, they determine their physiological function, because they allow
      cholinesterase subunits of type T to form oligomers and to associate with
      structural anchoring proteins. When reduced to their catalytic domain, AChE
      subunits without a t peptide are active but remain monomeric and soluble.

PMID- 17192682
TI  - The N-butylcarbamate derivative of galantamine acts as an allosteric potentiating
      ligand on alpha7 nicotinic receptors in hippocampal neurons: clinical
      implications for treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterized by cognitive impairments that become severe enough to interfere
      with the daily activities of patients and eventually lead to death (Chung and
      Cummings, 2000). Arecent study reports that approx 24 million people suffer from
      dementia worldwide. If the mortality rate does not change and no curative or
      preventive treatment is developed, this number is expected to double every 20 yr
      worldwide (Ferri et al., 2005). Although the causes of AD remain obscure, it has
      been reported that incremental loss of cholinergic neurons and of nicotinic
      receptor (nAChR) function/expression in specific brain regions correlates well
      with the severity of the symptoms at early stages of the disease (Hellstrom
      Lindahl et al., 1999; Nordberg, 2001; Perry et al., 2001; Wevers et al., 1999).
      In patients with more advanced stages of AD, such a correlation between the
      magnitude of nAChR loss and of cognitive decline does not appear to exist
      (Sabbagh et al., 2001). The nicotinic cholinergic system plays a central role in
      modulating different forms of associative learning known to be impaired in AD
      patients, including the eyeblink classical conditioning (Woodruff-Pak, 2001), and
      in maintaining neuronal viability. Neuroprotection and cognitive improvement
      result from increasing the activity of different nAChR subtypes, including those
      bearing the alpha7 subunit (Carlson et al., 1998; Hejmadi et al., 2003; Kihara et
      al., 1997; Levin et al., 2006). Thus, increasing nAChR activity in the brain was
      proposed as a mechanism to slow down the progression of the disease (Maelicke and
      Albuquerque, 1996).

PMID- 17192684
TI  - Conclusions and comments for the XII ISCM.
AB  - The first International Symposium on Cholinergic Mechanism (ISCM), organized by
      the late Edith Heilbronn, was held in Skokloster in 1970; Alicante's XII ISCM
      shows the exponential progress made in the cholinergic field in barely 30 years!
      Thus, Alzheimer's disease was not a topic at the first ISCM. The concept of
      homeostatic mechanisms regulating choline levels in the brain was not conceived
      of as yet. Three-dimensional pictures and the the protein structure of
      cholinergic receptors were not even thought of, as in 1970, we had only an
      "abstract" knowledge of receptors, based on SAR notions of Everhardus Ariens,
      Robert Furchgott, and Peter Pauling; in fact the Nobel Prize winner Furchgott
      stated in 1964 that "... with rare exceptions, we cannot ... identify the
      receptor as an individual chemical entity." Similarly, three-dimensional images
      of cholinesterases (ChEs) and the ChE "gorges" were unknown (Furchgott, 1964).
      The Whittakerian notion of synaptic vesicular release of acetylcholine (ACh) was
      the only version of the mode of ACh release, and the unorthodox opinions of Yves
      Dunant, Maurice Israel, Bruno Ceccarelli and Jacopo Meldolesi were still to be
      promulgated. Little was known about cholinergic correlates of behaviors such as
      learning and aggression, and there was no notion of cholinergic aspects of self
      awareness (consciousness), free will, and the active subconscious. And modern
      methodologies were unknown, including the measurements of ACh, such as the gas
      chromatography-mass spectrometry (GCMS) method, discovered by Israel Hanin, Don
      Jenden, and Bo Holmstedt in the 1950s, the chemiluminescence developed by Maurice
      Israel, Yves Dunant, and their associates (Israel et al., 1983), and
      crystallography and molecular biology techniques, such as the "knockout" (KO)
      mouse models.

PMID- 17192685
TI  - Safety and radiosensitizing efficacy of sanazole (AK 2123) in oropharyngeal
      cancers: randomized controlled double blind clinical trial.
AB  - Oropharynx is an important site of cancer in India. Global comparison indicates
      higher incidences in India. Radiotherapy remains an important treatment modality.
      Efforts to improve loco-regional treatment and prolong survival are areas of
      focus. Radiosensitizers in hypoxic tumors have shown promise. AIM: To study the
      safety and radiosensitizing efficacy of sanazole in oropharyngeal squamous cell
      carcinoma (stage T2-4, N0-3, M0) as phase-II double blind controlled trial in
      patients treated with conventional radiotherapy. SETTINGS AND DESIGN: Single
      institutional, randomized, double-blind, placebo-controlled trial. MATERIALS AND
      METHODS: Group 1 (control; n = 23) received normal saline infusion, group 2
      (test; n = 23) received sanazole biweekly 1.25 g intravenous infusion 15 minutes
      before radiotherapy. Surrogate end points of efficacy were tumor and nodal size;
      safety parameters were mucositis, salivary and skin reactions, dysphagia,
      vomiting, dysgeusia and neurological deficit. Investigators blinded to the trial
      evaluated patients, weekly during treatment for six weeks and thereafter monthly
      for three months. STATISTICAL METHODS: Non-parametric, Friedman's, Chi square,
      Mann-Whitney U tests. RESULTS: In the test, 15 (65%) patients had complete
      response, five (22%) partial/no response, two (9%) died, one (4%) lost to follow
      up. In the control, five (22%) patients had complete response, 16 (70%)
      partial/no response, one (4%) died, one (4%) lost to follow up. Short-term loco
      regional response was better in the test (DF = 3, 95% Confidence Interval 0.418,
      0.452, P = 0.0048). In the test group significant vomiting and one case of grade
      3 neurological deficit was observed. CONCLUSION: The study validates the
      usefulness of sanazole for initial loco-regional control in oropharyngeal
      cancers.

PMID- 17192686
TI  - High-risk human papillomavirus, tumor suppressor protein p53 and mitomycin-C in
      invasive squamous cell carcinoma cervix.
AB  - BACKGROUND: Clinical data relating to human papillomavirus (HPV) infection and
      p53 status in cervical cancer has been sparse and confusing. AIM: To evaluate
      high-risk HPV and expression of tumor suppressor protein p53 in squamous cell
      carcinoma of cervix and to assess response to mitomycin-C in neo-adjuvant
      chemotherapy. SETTING AND DESIGN: Teaching College Hospital; Gynecologic Oncology
      Unit and Department of Pathology. Prospective, randomized. MATERIALS AND METHODS:
      Expression of p53 protein was assessed, using immunohistochemistry with mouse
      monoclonal antibody in 30 consecutive patients undergoing radical hysterectomy or
      admitted for neo-adjuvant chemotherapy. Human papillomavirus DNA (HPV DNA) was
      assessed using hybrid capture II technology. Patients eligible for chemotherapy
      were randomized into vincristine, bleomycin and cisplatin (VBP) group and VBP
      with mitomycin C group. STATISTICAL ANALYSIS: Chi-square test, one-way ANOVA,
      Pearson's correlation; Mann-Whitney, McNemar and Fischer's exact tests were used
      for statistical analysis. RESULTS: All patients with cancer cervix were positive
      for high-risk HPV DNA having relative light units/cut off values ranging from 3.4
      2389.21 (P value = 0.006). High viral load of high risk HPV DNA was seen in
      advanced stages (P = 0.05) and an association of viral load with tumor volume was
      also seen (r = 0.361, P = 0.05). Analysis of p53 protein in cervical carcinoma
      patient showed expression in 50% of cancer specimens (P value < 0.001). McNemar's
      and Fischer's exact test showed no change in p53 status post-chemotherapy;
      however 66% of stage II B patients in VBP-M group became operable. CONCLUSION:
      High-risk HPV was universally present in all cases of cancer cervix and viral
      load was associated with stage and tumor volume while p53 protein was expressed
      in 50% of cases suggesting deregulation. More studies using mitomycin-C in
      cervical cancer treatment protocols are needed.

PMID- 17192687
TI  - Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and
      their relationship with HER-2/neu and hormonal receptors: impact on prognosis and
      therapy.
AB  - BACKGROUND: A number of studies have shown over-expression of cox-2 in breast
      cancer. Also it has been recorded that human breast cancer expresses high level
      of cox-2 and 12-lipoxygenase which may be beneficial in future therapy plan for
      those patients. AIMS: The present study aims to examine the level of transcripts
      of cox-2 and 12-lipoxygenase in Egyptian breast cancer patients and to compare
      between the expressions of both enzymes and TNM staging, hormone receptors status
      (including estrogen and progesterone) and HER2/neu expression. MATERIALS AND
      METHODS: Total cellular RNA was extracted from 64 frozen tissue samples of breast
      carcinoma and their corresponding normal adjacent tissues. Cox-2 and 12
      lipooxygenase expressions were detected using RT-PCR. Hormonal receptors as well
      as HER2/neu were detected immuno-histochemically for each patient. RESULTS: About
      47 and 62.5% of carcinoma samples showed over-expression of cox-2 and 12
      lipooxygenase respectively as compared to their corresponding normal tissues. The
      results revealed that cox-2 significantly associated with TNM staging (P =
      0.0047) and hormonal receptors status (P = 0.0201). The relationship between cox
      2 and HER2/neu expression was close to a significant value (P = 0.0747). 12
      lipooxygenase showed only significant association with TNM staging (P = 0.0076).
      Neither hormonal receptors nor HER2/neu showed significant association with this
      enzyme. CONCLUSION: Elevated levels of cox-2 and 12-lipoxygenase expression were
      detected in human breast cancer. Also, the results revealed that cox-2 and 12
      lipooxygenase mRNA expressions are associated with TNM staging in human breast
      cancer. Furthermore, there is an inverse association between cox-2 expression and
      hormonal receptor status. This observation may drive us to the possible role of
      those two enzymes in determining the plan of therapy of breast cancer patients.

PMID- 17192688
TI  - Meta-analysis of case-referent studies of specific environmental or occupational
      pollutants on lung cancer.
AB  - BACKGROUND: Meta-analysis is a statistical tool for combining and integrating the
      results of independent studies of a given scientific issue. The present
      investigation was initiated to investigate case-referent studies of lung cancer
      risk from specific environmental and occupational pollutants, using detailed
      individual exposure data. MATERIALS AND METHODS: To examine the risk of lung
      cancer associated with environmental and occupational pollutants, a meta-analysis
      of published case-control studies was undertaken using a random effects model.
      For this study, the papers were selected for review from electronic search of
      PubMed, Medline and Google Scholar during 1990-2006. The principal outcome
      measure was the odds ratio for the risk of lung cancer. Twelve study reports
      detailing the relationship between the lung cancer and the type of exposure were
      identified. RESULTS: The odds ratio of asbestos, cooking fuel, cooking fumes,
      motor and diesel exhaust related to lung cancer were 1.67, 1.99, 2.52 and 1.42 (P
      < 0.001), respectively. The odds ratio of metal fumes related to lung cancer was
      1.28 (0.001 P < 0.01). The combined odds ratio for the environmental and
      occupational exposure related to lung cancer was 1.67 (P < 0.001). CONCLUSIONS:
      The meta-analysis of the present study shows the magnitude association between
      asbestos, cooking fumes, cooking fuels, motor and diesel exhaust, with lung
      cancer risk. Lung cancer risk may be reduced by controlling exposure levels.

PMID- 17192689
TI  - Adjuvant chemo-radiotherapy in patients with gastric cancer.
AB  - BACKGROUND: The role of adjuvant therapy in gastric cancer has been
      controversial. AIM: In this study, we report our experience with adjuvant
      chemotherapy and radiotherapy in patients with non-metastatic gastric cancer.
      SETTINGS AND DESIGN: Fifty patients were reviewed and assigned to three
      therapeutic groups. MATERIALS AND METHODS: Twenty patients received radiotherapy
      with concomitant administration of 5-fluorouracil and leucovorin on the first and
      last three days of radiotherapy; 20 patients received a five-day cycle 5
      fluorouracil and leucovorin followed four to five weeks later by radiotherapy
      concomitant with the administration of fluorouracil on the first and the last
      three days of radiotherapy. Four weeks after radiotherapy two more five-day
      cycles of chemotherapy were administered; 10 patients received three cycles of
      cisplatin/docetaxel followed by radiotherapy and three additional cycles of
      chemotherapy after the completion of radiotherapy. STATISTICAL ANALYSIS: Patients
      were evaluated for treatment-related toxicity, local recurrences, distant
      metastases and deaths. We also aimed to make any possible comparisons between
      different chemo-radiation protocols. RESULTS: Within a median follow-up of 21.5
      months seven patients developed local recurrence and 17 patients developed
      distant metastases. The overall death proportion was 42% (95% CI 28.2-56.8%).
      Despite the limited number of patients, no statistically significant differences
      in local recurrences, distant metastases and deaths were observed between the
      three protocols. Acute and long-term treatment-related toxicity was low and no
      treatment-related deaths were observed. CONCLUSION: Despite variations of
      chemotherapy, our study demonstrated that combined chemo-radiotherapy for
      patients with resected gastric cancer can be administered safely, with acceptable
      toxicity.

PMID- 17192690
TI  - Prophylactic beclomethasone spray to the skin during postoperative radiotherapy
      of carcinoma breast: a prospective randomized study.
AB  - BACKGROUND AND AIMS: Radiation induced wet desquamation of skin in carcinoma
      breast patients is a painful condition. In this study topical beclomethasone
      dipropionate spray was used as prophylaxis with the purpose of reducing risk of
      the wet desquamation of skin in irradiated field. MATERIALS AND METHODS: Sixty
      patients of carcinoma breast were planned for postoperative loco regional
      radiotherapy (50 Gy in 25 fraction over five weeks) were prospectively randomized
      into two groups (1) steroid group-patients were advised to use beclomethasone
      dipropionate spray in irradiated axilla from day one of radiotherapy, (2) control
      group-patients were not allowed to use any topical agent in irradiated area.
      Radiation induced skin reaction was noted in terms of erythema, dry desquamation
      and wet desquamation weekly till end of prescribed 50 Gy dose of the radiation
      therapy. STATISTICAL METHOD: Chi-square test was used to see the statistical
      significance of the difference in wet desquamation between two arms of the study.
      Chi-square value and P-value was calculated for the difference of wet
      desquamation in two study arms. RESULT: In steroid group 4/30 (13.33%) patients
      developed wet desquamation of the axillary skin at the end of the radiotherapy.
      For the control group, this figure was 11/30 (36.66%). The difference in wet
      desquamation of the axillary skin in the two groups was statistically significant
      (P-value = 0.0369). CONCLUSION: Topical steroid (beclomethasone dipropionate
      spray) for skin during radiotherapy significantly reduces the risk of wet
      desquamation of the skin.

PMID- 17192691
TI  - Treatment of hyperlipidemia from Japanese evidence.
AB  - The treatment of hyperlipidemia is aimed at preventing cardiovascular disease
      (CVD) and coronary heart disease (CHD). As the incidence of CHD in Japan is about
      one-third lower and that of stroke is two-fold higher compared to Western
      countries, and the doses of lipid-lowering drugs used in foreign randomized
      controlled clinical trials (RCTs) are much higher than in general use in Japan,
      it remains unclear whether the results of RCTs conducted in Western countries
      could be extrapolated to Japanese patients. Recently, two major large-scale,
      prospective, RCTs in Japanese hypercholesterolmic patients, the Management of
      Elevated Cholesterol in the Primary Prevention of Adult Japanese (MEGA) study and
      the Japan EPA Lipid Intervention Study (JELIS), have been reported. Japanese
      epidemiological studies and Japanese clinical studies are reviewed. The evidence
      suggests that hypercholesterolemia, hypertriglyceridemia, and low HDL-cholesterol
      are strongly associated with increased CHD risk. Lipid-lowering medication shows
      beneficial effects even in low-risk populations; however, the data did not
      support that lower cholesterol is better. The safety and efficacy of
      hyperlipidemia treatment in Japanese patients are discussed.

PMID- 17192692
TI  - The possible contribution of a general glycosphingolipid transporter, GM2
      activator protein, to atherosclerosis.
AB  - We previously found that oxidized low-density lipoprotein (LDL) elevated the
      expression of mRNA of GalNAcbeta1-4[NeuNAcalpha2-3]Galbeta1-4Glc-Cer (GM2)
      ganglioside activator protein, in human monocyte-derived macrophages. Recently,
      GM2 activator protein has become known as a general glycosphingolipid transporter
      as well as a specific cofactor for the hydrolysis of GM2 ganglioside by lysosomal
      beta-hexosaminidase A. Accumulation of glycosphingolipids has been observed in
      the serum or aorta of atherosclerotic model animals and humans. The proliferation
      of aortic smooth muscle cells, elevation of LDL uptake by macrophages,
      interfering LDL clearance by the liver, and enhancement of platelet adhesion to
      collagen have been proposed as the underlying mechanisms of glycosphingolipid
      mediated atherogenesis. The GM2 activator protein can bind, solubilize and
      transport a broad spectrum of lipid molecules, indicating that GM2 activator
      protein may function as a general intra- and inter-cellular lipid transport
      protein. Collectively, elevated levels of GM2 activator protein in the aorta may
      be another feature of human atherosclerosis.

PMID- 17192693
TI  - Nitric oxide pathway activation and impaired red blood cell deformability with
      hypercholesterolemia.
AB  - The pathophysiological effects of the activation or inhibition of the nitric
      oxide (NO)-mediated pathway on the deformability of red blood cells (RBC) were
      evaluated in the presence of hypercholesterolemia induced in rabbits fed a
      cholesterol-rich diet. RBC deformability was assessed using a microchannel array
      flow analyzer system. The maximum passage time (MPT) by flowing a suspension of
      RBC through the microchannels was used as an index of RBC deformability. During
      cholesterol feeding for 12 weeks, MPT gradually increased with no significant
      elevation in the serum asymmetric dimethylarginine (ADMA) and arginine/ADMA
      ratio. The reduction in RBC deformability associated with hypercholesterolemia
      was significantly improved during incubation with each of three different NO
      pathway activators: a NO donor, 8-bromo-cyclic GMP, and arginine; however, no
      additional reduction was observed with ADMA administration. The inhibition of NO
      synthase due to ADMA caused a significant reduction in the deformability of
      normal RBC, which was reversed with NO pathway activation. These results suggest
      that impaired RBC deformability may be associated with a dysfunction in the NO
      pathway that is partially dependent upon the accumulation of ADMA in RBC, and
      exogenous NO pathway activators may improve the microcirculation by restoring RBC
      deformability in the presence of hypercholesterolemia.

PMID- 17192694
TI  - Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on
      ubiquinone levels in rat skeletal muscle and heart: relationship to cytotoxicity
      and inhibitory activity for cholesterol synthesis in human skeletal muscle cells.
AB  - Although statins are prescribed as relatively safe and effective drugs for
      hypercholesterolemic patients, it has been reported that a significant side
      effect, myopathy, occurs infrequently during medication. Moreover, because
      statins decrease cardiac ubiquinone levels, the risk of cardiac dysfunction has
      been suggested. This study sought to evaluate and compare the cytotoxicity of
      statins (cerivastatin, pitavastatin, fluvastatin, simvastatin, atorvastatin and
      pravastatin) in cultured human skeletal muscle cells (HSkMCs) and the effects on
      ubiquinone levels in statin-treated rat skeletal muscle and heart. Cerivastatin,
      the most potent inhibitor of HMG-CoA reductase, showed the strongest cytotoxicity
      (over 10-fold) among the statins examined, while the effects of the others were
      in a similar range. In rat experiments, neither pitavastatin nor cerivastatin
      decreased ubiquinone levels in skeletal muscle, but both dose-dependently lowered
      ubiquinone levels in the heart. As the rates of reduction by pitavastatin (9.6%
      at 30 mg/kg) and cerivastatin (9.7% at 0.3 mg/kg) were almost equal, it was
      estimated that cerivastatin reduced ubiquinone levels in the rat heart
      approximately 100-fold more strongly than pitavastatin, based on the effective
      doses. We found that cerivastatin showed the most potent cytotoxicity in HSkMCs
      and strongly lowered ubiquinone levels in the rat heart.

PMID- 17192696
TI  - Serum apolipoprotein j in health, coronary heart disease and type 2 diabetes
      mellitus.
AB  - Apolipoprotein (apo) J, clusterin, is ubiquitously expressed in many tissues, and
      is a component of high-density lipoproteins (HDLs). There is experimental
      evidence that it may be anti-atherogenic through its effects on cholesterol
      transport, smooth muscle cell proliferation and lipid peroxidation. HDLs
      containing apo J and apo A-I carry paraoxonase (PON1), which protects low-density
      lipoproteins from oxidative modification; however, the extent to which apo J
      affects coronary heart disease (CHD) is not known. We have developed a sandwich
      ELISA that enables apo J to be assayed in the range of 13-200 microg/mL. Serum
      apo J was 52.8+/-0.8 microg/mL (mean+/-SEM; range, 36.0-84.3 microg/mL; n=92) in
      healthy Japanese men, and 49.3+/-0.5 microg/mL (34.5-72.8; n=241) in healthy
      Japanese women. Multiple regression of these data and results from 67 men with
      CHD showed that apo J concentration was unrelated to age, sex or body mass index,
      but was positively related to serum PON1 (p<0.001) and apo B (p<0.02)
      concentrations. In women, it was also positively related to blood glucose
      (p<0.02). After adjusting for its associations with covariates, serum apo J
      averaged 5.4 microg/mL, lower in CHD men than in controls (p<0.003). Type 2
      diabetics had higher apo J concentrations (men, 83.1+/-3.4 microg/mL, n=64;
      women, 64.0+/-2.3 microg/mL, n=46) than healthy men and women (p<0.001). In these
      Type 2 diabetics, apo J concentration was unrelated to PON1 concentration, but
      was positively related to blood glucose (p<0.01). After adjustment for its
      relation to blood glucose, the mean apo J concentration was similar in diabetics
      and healthy subjects. These findings suggest that apo J may be anti-atherogenic
      in humans, and that its concentration is raised by Type 2 diabetes.

PMID- 17192695
TI  - A selective NFkappaB inhibitor, DHMEQ, reduced atherosclerosis in ApoE-deficient
      mice.
AB  - BACKGROUND AND PURPOSE: Atherosclerosis is a chronic inflammatory process, and
      anti-inflammatory agents potentially inhibit the development of atherosclerosis.
      We tested whether a novel NFkappaB inhibitor reduces atherosclerosis. METHODS:
      Dehydroxymethylepoxyquinomicin (10 mg/kg) or vehicle (chloromethyl cellulose) was
      injected intraperitoneally into apoE-deficient mice three times a week for 16
      weeks. The entire aorta was excised and atherosclerotic area was determined at 4
      and 16 weeks. Serum levels of cholesterol, triglyceride, TNF-alpha and
      adiponectin were also measured. RESULTS: The atherosclerotic area was
      significantly smaller in mice treated with dehydroxymethyl-epoxyquinomicin both
      at 4 and 16 weeks. There was no significant difference in body weight or serum
      levels of cholesterol, triglyceride, and adiponectin. CONCLUSIONS: A new NFkappaB
      inhibitor, dehydroxymethylepoxyquinomicin, reduced atherosclerosis without
      affecting plasma lipid levels in apoE-deficient mice.

PMID- 17192697
TI  - Cholesterol-years score is associated with development of senile degenerative
      aortic stenosis in heterozygous familial hypercholesterolemia.
AB  - We retrospectively evaluated the frequency and identified the factors associated
      with the development of aortic stenosis (AS) in 96 patients with heterozygous
      familial hypercholesterolemia (FH). The frequency of AS was 31% (4/13) and that
      of critical stenosis was 15% (2/13) in older patients over the age of 70 years.
      All 4 patients with AS were female aged more than 70 years who were diagnosed
      with FH when aged more than 60 years. There were no significant differences in
      conventional coronary risk factors; however, the age at cardiac catheterization,
      age at diagnosis of FH and the cholesterol-years score (CYS) with AS were
      significantly higher than those without AS (p=0.006, p=0.017, p=0.021,
      respectively). In multiple regression analysis, CYS was a significant independent
      predictor for the development of AS (p=0.037) in 13 older patients over the age
      of 70 years. These results suggest that physicians should be aware that AS needs
      attention in older patients with heterozygous FH, especially women who have been
      diagnosed late in life and those who have been inadequately treated.

PMID- 17192698
TI  - Distinct effects of pravastatin, atorvastatin, and simvastatin on insulin
      secretion from a beta-cell line, MIN6 cells.
AB  - In addition to the prevention of cardiovascular diseases by lowering plasma LDL
      cholesterol, recent studies suggest that statins could have some impact on
      insulin action. To estimate the direct effects of statins on insulin secretion
      from pancreatic beta-cells, MIN6 cells were treated with pravastatin,
      simvastatin, or atorvastatin. Basal insulin secretion at low glucose
      concentration was unexpectedly increased at very high doses of simvastatin or
      atorvastatin after 24- and 48-hour incubation. Insulin secretion at high glucose
      was not significantly changed, and thus, net glucose-stimulated insulin secretion
      was apparently decreased by these lipophilic statins. The changes in insulin
      secretion were highly associated with increased endogenous SREBP activities in
      response to HMG-CoA inhibition as estimated by SRE-luciferase assays, and finally
      after 48-hour incubation, accompanied by impaired cell viability as estimated by
      MTT assays. In contrast, these changes were much less prominent by the addition
      of pravastatin. Meanwhile, glucose-stimulated insulin secretion of islets
      isolated from C57BL/6 mice was not significantly changed by any of the statins.
      Overall, taken up by beta-cells, statins can affect insulin secretion through
      either HMG-CoA inhibition or cytotoxicity, as observed by the addition of
      extraordinary high doses of lipophilic statins, but not hydrophilic statins, to
      the medium.

PMID- 17192699
TI  - Separation of plasma lipoproteins.

PMID- 17192700
TI  - Effects of low-dose irradiation on enhancement of immunity by dendritic cells.
AB  - Low-doses of irradiation have been reported to have beneficial effects,
      particularly anti-tumor effects. In this paper, we show the effects of the low
      dose irradiation on T cell activation induced by dendritic cells (DCs). DCs,
      which had been pre-irradiated at 0.02-1.0 Gy from a (137)Cs source, were cultured
      with allogeneic T cells, and the proliferation of T cells was then examined. The
      0.05Gy-pre-irradiated DCs showed the highest proliferation capacity of T cells.
      The 0.05Gy-irradiation does not augment the expression of major
      histocompatibility complexes (MHCs) or costimulatory molecules on DCs, as with
      non-irradiated DCs or 1Gy-irradiated DCs, but does augment the production of IL
      2, IL-12 and IFN-gamma DCs. These results suggest that the low-dose irradiation
      augments T cell-activation capacity through cytokine production by DCs, which
      might shift naive helper T cells to Th1 cells.

PMID- 17192701
TI  - The role of the selective serotonin reuptake inhibitor fluoxetine in temperature
      regulation in ovariectomized rat models.
AB  - Thermoregulation is an integrated network of neuroendocrine, autonomic and
      somatosensory responses. Thermoregulatory dysfunction occurs during fluctuations
      or decline of gonadal hormone levels and results in vasomotor symptoms such as
      hot flushes and/or night-time sweating. The neurotransmitter serotonin (5-HT),
      has been reported to play a role in thermoregulation via changes in extracellular
      5-HT levels and/or activation of various 5-HT receptors. The purpose of this
      study was to evaluate the role of the selective 5-HT reuptake inhibitor (SSRI),
      fluoxetine (FLX), on temperature regulation using ovariectomized (OVX) rodent
      models of thermoregulation. Single, subcutaneous (s.c.) administration of FLX (3,
      10, 30 and 60 mg/kg) dose-dependently reduced core body temperature (CBT). FLX at
      3 and 10 mg/kg s.c. showed no statistically significant decrease on tail-skin
      temperature (TST), whereas at higher doses (30 and 60 mg/kg) a significant
      decrease in TST was noted in the telemetry model. To mimic chronic SSRI
      treatment, a 5-HT(1A) antagonist (WAY-100635; 0.3 mg/kg) was administered 20 min
      prior to FLX (10 mg/kg). This combination showed no significant improvement on
      temperature dysfunction compared to FLX alone. Similarly, in a morphine-dependent
      model of temperature dysfunction FLX, was inactive at 10 mg/kg whereas the 30 and
      60 mg/kg s.c. dose abated the naloxone-induced increase in TST by 55 and 81%,
      respectively. In summary, FLX affected CBT at all doses, but alleviated
      thermoregulatory dysfunction only at higher doses that are non-selective for the
      5-HT system.

PMID- 17192703
TI  - Regulation of the hypothalamic melanin-concentrating hormone neurons by sex
      steroids in the goldfish: possible role in the modulation of luteinizing hormone
      secretion.
AB  - In teleost fish, melanin-concentrating hormone (MCH) is a cyclic heptadecapeptide
      released from the pituitary during white background adaptation. In the periphery
      MCH concentrates melanin granules in melanophores thus lightening the body color
      of fish. Evidence from mammalian studies has demonstrated the involvement of MCH
      in the control of energy balance and the reproductive axis. Information about the
      hormonal regulation of MCH neurons in non-mammalian systems is scarce and nothing
      is known about its role in the regulation of the reproductive axis. We here
      report the molecular characterization of two MCH precursors in the goldfish. Both
      precursors are peripherally expressed and the expression in the central nervous
      system is restricted to the mediobasal hypothalamus. Hypothalamic MCH-mRNA
      production is upregulated during white background adaptation. Both testosterone
      and estradiol stimulate MCH mRNA expression in the hypothalamus in a sex
      dependent manner, with females showing the greatest responsiveness. In addition,
      in vitro experiments demonstrated that graded doses of salmon MCH stimulate LH,
      but not GH, secretion from dispersed pituitary cells. Results suggest that
      hypothalamic MCH may participate in the steroid positive feedback loop on
      pituitary LH secretion.

PMID- 17192702
TI  - Orexin A induces GnRH gene expression and secretion from GT1-7 hypothalamic GnRH
      neurons.
AB  - Orexin A, a recently discovered hypothalamic peptide, has been shown to have a
      stimulatory effect on release of gonadotropin-releasing hormone (GnRH) from rat
      hypothalamic explants in vitro. However, it is presently unclear whether in vivo
      this effect is mediated directly at the level of the GnRH neuron, or via multiple
      afferent neuronal connections. Therefore, in the present study, we investigated
      the direct action of orexin A on GnRH neurons using the immortalized GnRH
      secreting GT1-7 hypothalamic cells. Orexin-1 receptor (OX1R) expression was
      detected in GT1-7 cells by RT-PCR and Western blot. Results showed that 0.1-1 nM
      orexin A, when administered in culture media for 4 h, can significantly stimulate
      GnRH mRNA expression in GT1-7 cells (p < 0.05). Administration of 1 microM OX1R
      antagonist, SB-334867, completely blocked the observed orexin A responses in
      these cells, indicating that orexin A stimulation of GnRH neurons is specifically
      through OX1R. Moreover, 0.1 nM orexin A stimulated GnRH release after 30-45 min.
      To examine possible signal transduction pathways involved in mediating these
      effects, a MEK inhibitor (UO-126), PKC inhibitor (calphostin C), and PKA
      inhibitor (H-89), were used, with each blocking orexin A-induced GnRH
      transcription and release from immortalized cells. Collectively, our results show
      that orexin A is capable of directly stimulating GnRH transcription and
      neuropeptide release from these immortalized hypothalamic neurons, and that the
      effects of orexin A appear to be mediated via the OX1R, coupled with activation
      of the PKC-, MAPK- and PKA-signaling pathways. It is suggested that the
      stimulatory effect of orexin A on GnRH transcription and release may also occur
      directly at the level of GnRH neurons in vivo.

PMID- 17192704
TI  - Pathophysiology of stroke rehabilitation: the natural course of clinical
      recovery, use-dependent plasticity and rehabilitative outcome.
AB  - Even though the disruption of motor activity and function caused by stroke is at
      times severe, recovery is often highly dynamic. Recuperation reflects the ability
      of the neuronal network to adapt. Next to an unmasking of latent network
      representations, other adaptive processes, such as excitatory metabolic stress,
      an imbalance in activating and inhibiting transmission, leading to salient
      hyperexcitability, or the consolidation of novel connections, prime the plastic
      capabilities of the system. Rehabilitative interventions may modulate mechanisms
      of neurofunctional plasticity and influence the natural course after stroke, both
      positively, but potentially also acting detrimentally. Though routine
      rehabilitative procedures are an integral part of stroke care, evidence as to
      their effectiveness remains equivocal. The present review describes the natural
      course of motor recovery, focusing on ischemic stroke, and discusses use- and
      training-dependent adaptive effects. It complements a prior article which
      highlighted the pathophysiology of plasticity. Though the interaction between
      rehabilitation and plasticity remains elusive, an attempt is made to clarify how
      and to what extent rehabilitative therapy shapes motor recovery.

PMID- 17192705
TI  - Mild mechanical traumas are possible risk factors for cervical artery dissection.
AB  - BACKGROUND AND PURPOSE: Cervical artery dissection (CAD) is a common cause of
      ischemic stroke in younger aged subjects. Retrospective studies suggest cervical
      manipulative therapy (CMT) and preceding infections as extrinsic risk factors for
      CAD. In a case-control study, we assessed a questionnaire with 7 mild mechanical
      traumas as potential trigger factors for CAD, including CMT and recent
      infections. PATIENTS AND METHODS: Forty-seven consecutive patients with CAD were
      compared with 47 consecutive patients of similar age with ischemic stroke due to
      etiologies other than CAD. Patients underwent a standardized face-to-face
      interview. We assessed head or neck pain and recent infection <7 days before
      symptom onset, as well as the following mechanical trigger factors <24 h and <7
      days prior to symptom onset: (1) heavy lifting, (2) sexual intercourse, (3) mild
      direct or (4) indirect neck trauma, (5) jerky head movements, (6) sports
      activity, and (7) CMT. RESULTS: We found no association between any single one of
      the above risk factors and CAD. CMT (CAD, n = 10; non-CAD, n = 5) and recent
      infections (CAD, n = 18; non-CAD, n = 10) were more frequent in the CAD group but
      failed to reach significance. However, the cumulative analysis of all mechanical
      trigger factors revealed a significant association of mechanical risk factors as
      a whole in CAD <24 h prior to symptom onset (p = 0.01). CONCLUSION: Mild
      mechanical stress, including CMT, plays a role as possible trigger factor in the
      pathogenesis of CAD. CMT and recent infections alone failed to reach significance
      during the present investigation, presumably due to the relatively small sample
      size of the study cohort.

PMID- 17192706
TI  - Is osteoarthritis an infection-associated disease and a target for chemotherapy?
AB  - The treatment of osteoarthritis (OA) continues to be a challenge, and current
      treatment modalities are disappointing. New approaches in therapy may be
      developed as a result of evidence of the involvement of inflammatory cytokines in
      the progression of OA. Cotrimoxazole (sulfamethoxazole/trimethoprim) was noted to
      have anti-inflammatory properties and has been used in the therapy of several
      autoimmune diseases. Analyzing our own and world experience, we propose that OA
      and degenerative joint and spine disease might be infection-associated diseases
      and a target for sulfamethoxazole/trimethoprim therapy.

PMID- 17192708
TI  - Differing effects of T4 DNA ligase in the modulation of the damage induced in
      mammalian cells by either X-rays or restriction endonucleases.
AB  - BACKGROUND: Of the different lesions induced by X-rays, DNA double-strand breaks
      (DSBs) are considered the main cause of chromosomal aberrations and cell death.
      Restriction endonucleases (REs) induce only DNA DSBs and have frequently been
      used to mimic the effects of ionizing radiation in the study of DNA damage and
      repair. METHODS: The present work makes use of clonogenic and cytogenetic assays
      to study the effect of T4 DNA ligase on modulating the damage induced by either X
      rays or an RE (MspI) that produces breaks with cohesive ends. A CHO cell line
      defective in ligase III activity (EM9) and its corresponding parental line (AA8)
      were used. RESULTS: Our results show that T4 DNA ligase increased cell survival
      and decreased chromosomal aberrations in cells treated with MspI, suggesting that
      most RE-induced DSBs can be repaired by a simple ligation. This enzyme was,
      however, unable to promote repair of the DNA damage induced by X-rays. Analysis
      of the ratios of exchange-type aberrations to chromatid break-type aberrations
      indicated that T4 ligase increased misrejoining of the DNA damage induced by X
      rays. The results were similar in EM9 and AA8 cells, although the effect was
      greater in the cells deficient in DNA strand break rejoining. In addition,
      depending on whether the end strand break structure is 3'-hydroxyl and 5'
      phosphoryl (REs) or more complex (X-rays), T4 DNA ligase could either promote the
      correct repair or, conversely, increase misrejoining. CONCLUSION: The present
      results confirm the idea that DNA DSBs induced by cohesive cutting RE are
      repaired by different mechanisms than those induced by X-rays causing cell
      lethality.

PMID- 17192707
TI  - Telithromycin inhibits the number of viable bacteria but not lymphocyte
      accumulation in a murine model of chronic respiratory infection.
AB  - The 14-membered macrolides, such as clarithromycin (CAM) and erythromycin (EM),
      are effective against diffuse panbronchiolitis. However, there have been no
      studies on the effects of telithromycin (TEL) on chronic respiratory infection in
      vivo. In this study, we determined the effect of TEL on an experimental murine
      model of chronic respiratory infection caused by Pseudomonas aeruginosa with
      biofilm formation. TEL significantly reduced the number of viable bacteria but
      had no effect on the proliferation of lymphocytes. In contrast, CAM decreased the
      number of lymphocytes but had no effect on the number of viable bacteria in the
      lung. These results suggest that TEL and CAM have different effects on chronic
      respiratory infection caused by P. aeruginosa.

PMID- 17192710
TI  - Interactions of antiretroviral drugs with anti-infectives and other
      antiretrovirals.
AB  - Combination antiretroviral (ARV) treatment is a potent and effective therapy for
      human immunodeficiency virus infection. Unfortunately, ARV drugs frequently
      interact among themselves, as well as with other anti-infectives. These
      interactions determine positive or negative consequences resulting in
      recommendations to avoid some combinations or to adjust the dosage of
      coadministered drugs. The effective clinical use of ARVs requires deep knowledge
      of interaction mechanisms and the consequent recommendations when coadministering
      interacting ARVs with other anti-infectives. A brief review of the present
      knowledge on interactions of ARVs with anti-infective drugs is presented.

PMID- 17192709
TI  - Comparison of essential oils from three plants for enhancement of antimicrobial
      activity of nitrofurantoin against enterobacteria.
AB  - BACKGROUND: Piperitone from plant essential oils enhancesbactericidal activities
      of nitrofurantoin and furazolidone against bacteria from the family
      Enterobacteriaceae. In this study, the essential oils of spearmint (Mentha
      spicata L.), dill (Anethum graveolens L.) and peppermint (Mentha piperita L.)were
      screened for augmentation of nitrofurantoin activity and the most active
      components were determined. METHOD: The effects of essential oils and their
      components on the bactericidal activity of nitrofurantoin against Enterobacter
      cloacae were studied using disk-diffusion and agar-dilution methods. The
      composition of essential oils was studied using gas chromatography-mass
      spectrometry. RESULTS: M. spicata and A. graveolens oils exhibited the highest
      effects. Gas chromatography-mass spectrometry analysis showed that the oils of
      these two plants contained 40.12 and 20.32% carvone, respectively. Pure carvone
      and piperitone equally increased the bactericidal activity of nitrofurantoin.
      Other ingredients of essential oils, including camphor, limonene and menthone,
      were less effective.

PMID- 17192711
TI  - Upregulation of enzymes metabolizing 5-fluorouracil in colorectal cancer.
AB  - BACKGROUND: The purpose of this study was to compare the activities of various
      enzymes, participating in the metabolism of 5-fluorouracil, between colorectal
      cancer and nontumor tissues and to investigate the association of the enzyme
      activities with clinicopathological backgrounds. METHODS: Activities of seven
      enzymes involved in nucleic acid metabolism--orotate phosphoribosyltransferase
      (OPRT), ribonucleotide reductase (RNR), thymidylate synthase, dihydropyrimidine
      dehydrogenase, thymidine phosphorylase, uridine phosphorylase and thymidine
      kinase (TK)--were measured in tumor and nontumor tissues from 28 patients who
      were operated on for colorectal cancers. RESULTS: OPRT, thymidylate synthase,
      RNR, thymidine phosphorylase, uridine phosphorylase and thymidine kinase
      activities were significantly higher in tumor areas than in nontumor areas. OPRT
      showed the highest T/N ratio (the ratio of each enzyme activity in tumor areas to
      that in nontumor areas). The T/N ratio of RNR activity showed a tendency to be
      associated with lymph node metastasis and Dukes classification. CONCLUSION: The
      results suggest that OPRT is a main enzyme participating in the phosphorylation
      of 5-fluorouracil and has an important role in tumor growth. The T/N ratio of RNR
      may be predictive of tumor progression.

PMID- 17192713
TI  - A negative finding in an exercise test is reliable among elderly people: a follow
      up study.
AB  - BACKGROUND: Coronary heart disease (CHD) is very common among elderly people.
      OBJECTIVE: To specify the diagnostic value of bicycle exercise tests conducted
      for elderly patients by trained general practitioners in primary health care.
      METHODS: We performed a 2-year follow-up study at the Kangasala Health Centre,
      Finland. The study population comprised all patients at least 60 years old (n =
      311) suspected of having CHD without prior diagnosis who were examined by an
      exercise test carried out by trained general practitioners during a period of 3
      years. Specificity and sensitivity as well as positive and negative predictive
      values of the tests were calculated based on whether or not the participants had
      a diagnosis of CHD by the end of the follow-up period. The numbers of patients
      referred for coronary angiography and bypass operation were registered. For
      analysis, the patients were divided into two age categories: 60-69 years and
      >or=70 years. RESULTS: A negative finding in the test proved very reliable: CHD
      manifested in only 3% of these cases in both age groups. The specificity of the
      test was 72% in the group 60-69 years and 66% in the group >or=70 years; the
      sensitivity values were 81 and 67%, respectively. The positive predictive values
      were 26 and 12%, the negative predictive value was 97% in both age groups. 1 in 4
      patients yielding a positive finding eventually underwent coronary angiography
      and 1 in 6 patients coronary bypass surgery. CONCLUSIONS: Exercise tests may
      predict the clinical outcome of CHD among elderly patients. A negative finding in
      an exercise test is very reliable.

PMID- 17192714
TI  - Teach the teachers: an observational study on mentor traineeship in gynecological
      laparoscopic surgery.
AB  - BACKGROUND: To evaluate the effect of a mentor traineeship in laparoscopic
      surgery in a teaching hospital. METHOD: This observational study was performed
      between January 1997 and December 2004 at Bronovo Hospital, The Hague, The
      Netherlands. Since January 2001, an advanced endoscopic gynecologist has mentored
      a trainee in laparoscopic surgery. Data on the trainee's procedures preceding
      (1997-2000) and during the mentor traineeship (2001-2004) were compared. The
      number and type of procedures performed, complications and conversions were
      derived from a prospectively kept database supplemented by a retrospective chart
      review. Operating times for total laparoscopic hysterectomy (TLH) were registered
      to establish the trainee's learning curve. RESULTS: Since the presence of a
      mentor, the trainee has performed significantly more advanced laparoscopic
      procedures. Despite the significant increase in advanced cases, the trainee's
      laparoscopic conversion rate to laparotomy remained stable between period 1 and
      period 2 (7.5 and 4.5%, respectively, p = 0.35, 95% CI -0.033 to 0.092);
      moreover, for level-3 procedures the conversion rate decreased (p < 0.001, 95% CI
      0.30-0.71). Despite the increase in advanced cases, the total complication rate
      remained stable (3.2-4.5%, p = 0.62, 95% CI -0.07 to 0.04) including the number
      of level-3 complications (p = 0.63, 95% CI -0.4 to 0.3). A decreasing trend in
      operating time for TLH was found; however, this was not significant (Spearman
      correlation coefficient -0.421, p = 0.81). CONCLUSIONS: Mentor traineeship in
      gynecology enhanced the advanced laparoscopic caseload. With the increase in
      advanced procedures, no increase in conversion rate, complication rate or
      operating times for TLH was found. Due to the mentorship, patients were not
      exposed to increased complications and conversions, or to the disadvantages of a
      prolonged operating time. Predominantly, mentor traineeship facilitated the
      implementation of laparoscopic surgery into an established gynecological practice
      in a teaching hospital.

PMID- 17192712
TI  - Effects of donepezil on central processing speed and attentional measures in
      Parkinson's disease with dementia and dementia with Lewy bodies.
AB  - BACKGROUND: We examined attention-enhancing effects of the cholinesterase
      inhibitor donepezil in Dementia with Lewy bodies (DLB) and Parkinson's disease
      with dementia (PDD) by means of open label study. METHODS: 22 DLBs and 23 PDDs
      were assessed over 20 weeks using the Cognitive Drug Research Computerized
      Attentional Tasks. We examined how much closer our patients moved towards being
      normal for their age by comparing them to a non-demented elderly control sample
      (n = 183, aged 71-75 years). RESULTS: Donepezil treatment improved power of
      attention, continuity of attention and reaction time variability. The deficit in
      responses was moved towards normal by 38 and 56% for power of attention and 22
      and 10% for continuity of attention in PDD and DLB, respectively. CONCLUSIONS:
      Improvements in attention were found with donepezil in PDD and DLB.

PMID- 17192715
TI  - Tuboovarian abscess caused by Candida in a woman with an intrauterine device.
AB  - Candida infection should be considered in an individual with a pelvic abscess
      that is unresponsive to conventional antibiotic therapy, particularly in the
      presence of an intrauterine device. We present a case of a tuboovarian abscess
      caused by Candida species in a woman with an intrauterine device for >10 years.
      Surgical intervention followed by antifungal therapy resulted in a favorable
      outcome.

PMID- 17192716
TI  - Monoclonal antibodies against the candidate lupin allergens alpha-conglutin and
      beta-conglutin.
AB  - BACKGROUND: The ingestion of dietary products containing sweet lupin (such as
      Lupinus albus or Lupinus angustifolius) has been reported to cause IgE-mediated
      allergic reactions. Recent studies have indicated lupin globulins as important
      IgE binding proteins. The aim of the present study was to generate and
      characterize monoclonal antibodies (mAbs) against lupin seed proteins. METHODS:
      Mice were immunized with a protein isolate from L. albus and mAbs were obtained
      by hybridoma techniques. Albumins and globulins were extracted, and the globulin
      fraction was separated further into conglutins by anion exchange chromatography.
      Specificities, binding patterns and applications of the mAbs were investigated by
      immunochemical methods. RESULTS: Five mAbs were produced: Lu11 (an IgG2b
      antibody), Lu8, Lu18, Lu34 and Lu35 (all IgM antibodies). The mAbs reacted
      strongly with protein isolates from both L. albus and L. angustifolius. All mAbs
      are directed towards the lupin globulin fraction; Lu11 and Lu18 recognize alpha
      conglutin, while Lu8, Lu34 and Lu35 recognize beta-conglutin. In addition, Lu11
      inhibited the binding of IgE from patients with positive skin prick tests to
      lupin proteins in a competitive ELISA by approximately 30%. Furthermore,
      preliminary results show that Lu11 can be used to develop a sensitive method for
      the detection of alpha-conglutin in foods. CONCLUSIONS: Lupin globulins are
      immunogenic and alpha-conglutin is a potential allergen. This is the first study
      describing mAbs against the candidate lupin allergens, emphasizing the importance
      of additional studies on conglutins in lupin allergy.

PMID- 17192717
TI  - Characterization of genes for a pollen allergen, Cry j 2, of Cryptomeria
      japonica.
AB  - BACKGROUND: Cry j 2 is one of the major pollen allergens of Cryptomeria japonica.
      The polymorphism of Cry j 2 isoforms and the conservation of the structure of Cry
      j 2 in coniferous species remain to be analyzed. METHODS: A cDNA library derived
      from the pollen of C. japonica was screened using a fragment of Cry j 2 cDNA.
      Restriction fragment length polymorphism analysis was performed to examine the
      diversity of Cry j 2 genes. The promoters of Cry j 2 genes were isolated with a
      commercially available cloning kit. Clonal variations in the expression of Cry j
      2 in pollen were examined by RNA gel blot analysis, and the conservation of the
      structure of the Cry j 2 gene in coniferous species was evaluated by DNA gel blot
      analysis. RESULTS: We isolated three cDNA clones encoding novel isoforms of Cry j
      2. We also sequenced a total of 16 promoter regions from 10 specimens. The
      sequences of promoter regions of Cry j 2 genes were highly divergent. The amount
      of Cry j 2 mRNA also varied considerably. The Cry j 2 gene was found to be
      conserved among species belonging to Taxodiaceae and Cupressaceae but to vary
      between Taxodiaceae and Pinaceae. CONCLUSIONS: The coding and promoter regions of
      Cry j 2 genes contain large numbers of polymorphisms. Our analysis revealed large
      variations in the expression of Cry j 2 at the transcriptional level, and we
      suggest that conserved homologs of Cry j 2 confer cross-allergenicity among
      Taxodiaceae and Cupressaceae.

PMID- 17192718
TI  - Rice: another potential cause of food allergy in patients sensitized to lipid
      transfer protein.
AB  - Recent studies show that the lipid transfer protein (LTP), the major Rosaceae
      allergen in patients not sensitized to birch pollen, is a largely cross-reacting
      allergen. Moreover, it is a potentially hazardous allergen due to its stability
      upon thermal treatment and pepsin digestion. The present study reports 3 cases of
      rice-induced anaphylaxis in LTP-allergic patients. In vitro inhibition studies,
      carried out using LTP purified from both rice and apple as well as whole peach
      extract, show that LTP was the relevant allergen in these patients and
      demonstrate the cross-reactivity between rice LTP and peach/apple LTP.

PMID- 17192719
TI  - Two-photon microscopy of vital murine elastic and muscular arteries. Combined
      structural and functional imaging with subcellular resolution.
AB  - Understanding vascular pathologies requires insight in the structure and
      function, and, hence, an imaging technique combining subcellular resolution,
      large penetration depth, and optical sectioning. We evaluated the applicability
      of two-photon laser-scanning microscopy (TPLSM) in large elastic and small
      muscular arteries under physiological conditions. Elastic (carotid) and muscular
      (uterine, mesenteric) arteries of C57BL/6 mice were mounted in a perfusion
      chamber. TPLSM was used to assess the viability of arteries and to visualize the
      structural components elastin, collagen, nuclei, and endothelial glycocalyx (EG).
      Functionality was determined using diameter changes in response to noradrenaline
      and acetylcholine. Viability and functionality were maintained up to 4 h,
      enabling the assessment of structure-function relationships. Structural vessel
      wall components differed between elastic and muscular arteries: size (1.3 vs. 2.1
      microm) and density (0.045 vs. 0.57 microm(-2)) of internal elastic lamina
      fenestrae, smooth muscle cell density (3.50 vs. 1.53 microm(-3)), number of
      elastic laminae (3 vs. 2), and adventitial collagen structure (tortuous vs.
      straight). EG in elastic arteries was 4.5 microm thick, covering 66% of the
      endothelial surface. TPLSM enables visualization and quantification of
      subcellular structures in vital and functional elastic and muscular murine
      arteries, allowing unraveling of structure-function relationships in healthy and
      diseased arteries.

PMID- 17192720
TI  - Insulin-degrading enzyme haplotypes affect insulin levels but not dementia risk.
AB  - BACKGROUND: Insulin-degrading enzyme (IDE) polymorphism is hypothesized to
      regulate insulin levels as well as processes involved in neuronal compromise
      found in dementia. METHODS: We examined the association of IDE haplotypes with
      dementia and insulin levels in a single well-characterized cohort of Japanese
      American men born between 1900 and 1919 and followed since 1965. In 1991, a
      fasting insulin was obtained; dementia cases were ascertained in 1991 and 1994 in
      a multi-stage procedure, diagnoses were made according to international
      guidelines. Five single-nucleotide polymorphisms were genotyped and used for
      haplotype analysis in a sample of 179 Alzheimer's disease cases, 104 vascular
      dementia cases and 516 controls nested in the total cohort. RESULTS: The global
      test for the haplotype effect on insulin levels was significant (p < 0.0001),
      adjusting for age, education, apolipoprotein epsilon4 status and fasting glucose.
      CONCLUSION: There was no association of IDE haplotypes with the risk of dementia.
      This study suggests IDE may be indirectly related to dementia via its regulation
      of insulin levels, but it is not a major gene for Alzheimer's.

PMID- 17192721
TI  - Association of tau haplotype-tagging polymorphisms with Parkinson's disease in
      diverse ethnic Parkinson's disease cohorts.
AB  - BACKGROUND: The overlap in the clinical and pathological features of tauopathies
      and synucleinopathies raises the possibility that the tau protein may be
      important in Parkinson's disease (PD) pathogenesis. Several MAPT polymorphisms
      that define the tau H1 haplotype have been investigated for an association with
      PD with conflicting results; however, two meta-analyses support an association
      between haplotype H1 and PD. METHODS: In this study, we recruited 508 patients
      and 611 healthy controls from Greek, Finnish and Taiwanese populations. We
      examined the possible genetic role of variation within MAPT in PD using haplotype
      tagging single polymorphisms (SNPs) in these ethnically different PD populations.
      RESULTS: We identified a moderate association at SNP rs3785883 in the Greek
      cohort for both allele and genotype frequency (p = 0.01, p = 0.05, respectively)
      as well as for SNP rs7521 (genotype p = 0.02) and rs242557 (p = 0.01 genotypic, p
      = 0.04 allelic) in the Finnish population. There were no significant differences
      in genotype or allele distribution between cases and controls in the Taiwanese
      cohort. CONCLUSION: We failed to demonstrate a consistent association between the
      MAPT H1 haplotype (delineated by intron 9 ins/del) and PD in three ethnically
      diverse populations. However, the data presented here suggest that subhaplotypes
      of haplotype H1 may confer susceptibility to PD, and that either allelic
      heterogeneity or different haplotype composition explain the divergent haplotype
      results.

PMID- 17192722
TI  - Genetic association study on colony-stimulating factor 1 in Alzheimer's disease.
AB  - BACKGROUND: Colony-stimulating factor 1 (CSF1) regulates the proliferation and
      differentiation of myelomonocytic cells. Microglial cells of CSF1-deficient mice
      are reduced in number and are functionally impaired. CSF1-deficient mice exhibit
      subtle neurodevelopmental defects, enhanced neuronal vulnerability. Moreover, it
      has been reported that these mice may have amyloid-plaque-like depositions in the
      brain at an early age. The human CSF1 gene maps to chromosome 1p21-p13, a region
      previously linked to Alzheimer's disease (AD). Thus, CSF1 is a functional and
      positional candidate gene for AD. OBJECTIVE: We assessed if genetic variability
      of CSF1 may influence the risk for AD. METHODS: We conducted a population-based
      case-control association study with 3 single nucleotide polymorphisms (SNPs)
      across the CSF1 locus in a sample of n = 185 (rs3093054, rs756325) and n = 327
      (rs1058885) individuals. RESULTS: None of the 3 investigated SNPs was associated
      with the risk for AD in our sample. CONCLUSION: These data do not support the
      hypothesis that genetic variability of CSF1 influences the risk for AD.

PMID- 17192723
TI  - The fly as a model for neurodegenerative diseases: is it worth the jump?
AB  - Neurodegenerative diseases are responsible for agonizing symptoms that take their
      toll on the fragile human life. Aberrant protein processing and accumulation are
      considered to be the culprits of many classical neurodegenerative diseases such
      as Alzheimer's disease, tauopathies, Parkinson's disease, amyotrophic lateral
      sclerosis, hereditary spastic paraplegia and various polyglutamine diseases.
      However, recently it has been shown that toxic RNA species or disruption of RNA
      processing and metabolism may be partly to blame as clearly illustrated in spinal
      muscular atrophy, spinocerebellar ataxia 8 and fragile X-associated tremor/ataxia
      syndrome. At the dawn of the twenty-first century, the fruit fly or Drosophila
      melanogaster has taken its place at the forefront of an uphill struggle to unveil
      the molecular and cellular pathophysiology of both protein- and RNA-induced
      neurodegeneration, as well as discovery of novel drug targets. We review here the
      various fly models of neurodegenerative conditions, and summarise the novel
      insights that the fly has contributed to the field of neuroprotection and
      neurodegeneration.

PMID- 17192724
TI  - Characterization of two novel missense mutations in the AQP2 gene causing
      nephrogenic diabetes insipidus.
AB  - Here, we report the aquaporin 2 (AQP2) mutational analysis of a patient with
      nephrogenic diabetes insipidus heterozygote due to two novel missense mutations.
      Direct sequencing of DNA in the male patient revealed that he was compound
      heterozygote for two mutations in the AQP2 gene: a thymine-to-adenine
      transversion at position 450 (c.450T>A) in exon 2 and a guanine-to-thymine at
      nucleotide position 643 (c.643G>T) in exon 4. The double heterozygous 450T>A and
      643G>T transversion causes the amino acid substitution D150E and G215C. Direct
      sequencing of exons 2 and 4 of the AQP2 gene from each of the parents revealed
      that the c.450T>A mutation was inherited from the father while the c.643G>T
      mutation was inherited from the mother. Analysis of AQP2 excretion demonstrated
      that no AQP2 was detectable in the urine of the proband, whereas normal AQP2
      levels were measured in both parents. When expressed in renal cells, both
      proteins were retarded in the endoplasmic reticulum and no redistribution was
      observed after forskolin stimulation. Of note, homology modeling revealed that
      the two mutations involve two highly conserved residues providing important clues
      about the role of the wt residues in AQP2 stability and function.

PMID- 17192725
TI  - Peyronie's disease: lights and shadows.
AB  - Peyronie's disease (PD) is characterized by the onset of fibrous plaque inside
      the tunica albuginea of the penile corpora cavernosa that can cause pain and
      bending during the erection, making intercourse difficult or impossible. Evidence
      of the literature supports the autoimmune etiology of PD and suggests genetic and
      familiar conditions, penile traumatisms, and a history of genital tract diseases
      as risk factors, but no definitive conclusions arise about the pathogenesis of
      the disease. Few randomized trials demonstrated that medical therapies, such as
      vitamin E, colchicine, potassium aminobenzoate, tamoxifen, and injection therapy
      with verapamil, can stabilize the acute phase of the disease. Extracorporeal
      shock wave therapy and iontophoresis cannot be considered first-line or gold
      standard therapies. Satisfactory results have been published with the Nesbit
      operation in large series with low-stage disease, whereas plication procedures
      have shown significant relapse rates. A high incidence of long-term penile
      retractions has been reported in high-stage disease treated with plaque incision
      and simple graft insertion. Malleable, soft, or inflatable prostheses combined
      with graft implantation have given the best results in terms of penile
      straightening and lengthening and patient satisfaction. In conclusion, the
      etiopathogenesis of PD is not yet clearly understood, no medical therapy is fully
      effective, and surgery remains the gold standard in patients with severe
      deformity and/or erectile dysfunction.

PMID- 17192726
TI  - Successful microsurgical penile replantation after a workplace injury.
AB  - Microsurgical techniques offer the opportunity for successful replantation of the
      amputated penis. We report the case of a patient who sustained a traumatic penile
      amputation as a result of a workplace accident. Microsurgical replantation was
      achieved with combined urological and plastic surgical input.

PMID- 17192727
TI  - Presentation and outcome of emphysematous renal tract disease in patients with
      diabetes mellitus.
AB  - BACKGROUND: Emphysematous renal tract disease (ERTD) is a rare necrotizing
      infection of the renal parenchyma and urinary tract caused by gas-producing
      organisms. ERTD deserves special attention because of its life-threatening
      potential. OBJECTIVES: To study the clinical features, radiological
      classification and prognostic factors of ERTD; and to compare the modalities of
      management and the outcome among the various radiological classes of ERTD.
      PATIENTS AND METHODS: Twenty consecutive patients with diabetes and ERTD, seen
      over last 3 years in a tertiary care institute of north India, were included in
      the study. All patients were subjected to computerized tomography (CT) after
      initial diagnosis by ultrasonography. They were classified into 5 classes as
      previously described. All patients included in the study were conservatively
      managed with appropriate antibiotics and/or percutaneous drainage or surgery if
      required. RESULT: Mean age (+/- SD) of these subjects was 54.4 +/- 20.6 years;
      duration of diabetes mellitus 8.6 +/- 5.8 years, and duration of symptoms related
      with ERTD ranged from 3 days to 3 months. Two patients had isolated emphysematous
      cystitis, 13 patients had emphysematous pyelonephritis (EPN), 3 had both EPN and
      cystitis, and 1 patient had EPN with cholecystitis, and 1 patient had EPN with
      pyomyositis. Only 7 (35%) patients had a history of pneumaturia. Escherichia coli
      was the commonest microorganism. The radiological distribution in 18 (2 had
      isolated cystitis) patients with EPN was: 2 patients had class 1; 1 had class 2;
      2 had class 3A; 11 had class 3B, and 2 had class 4. Of 20 patients 11 (55%)
      survived. However, those patients who died had severe EPN based on radiological
      class (6 had class 3B and 1 had class 4). There was no significant difference
      between the survivor and non-survivor groups with respect to age, gender,
      duration of diabetes mellitus, duration of symptoms, serum creatinine level,
      total leukocyte count, hemoglobin, platelet count and culture positivity.
      CONCLUSION: Computerized tomographic class 3B or 4 is the most reliable predictor
      of outcome in patients with ERTD.

PMID- 17192728
TI  - Different types of scaffolds for reconstruction of the urinary tract by tissue
      engineering.
AB  - INTRODUCTION: Tissue engineering is an important and expanding field in
      reconstructive surgery. The ideal biomaterial for urologic tissue engineering
      should be biodegradable and support autologous cell growth. We examined different
      scaffolds to select the ideal material for the reconstruction of the bladder wall
      by tissue engineering. MATERIALS AND METHODS: We seeded mouse fibroblasts and
      human keratinocytes in a co-culture model on 13 different scaffolds. The cell
      seeded scaffolds were fixed and processed for electron microscopy, hematoxylin
      and eosin stain, and immunohistochemistry. Cell density and epithelial cell
      layers were evaluated utilizing a computer-assisted optical measurement system.
      RESULTS: Depending on the growth pattern, scaffolds were classified into the
      following three distinct scaffold types: carrier-type scaffolds with very small
      pore sizes and no ingrowth of the cells. This scaffold type induces a well
      differentiated epithelium. Fleece-type scaffolds with fibers and huge pores. We
      found cellular growth inside the scaffold but no epithelium on top of it. Sponge
      type scaffolds with pores between 20 and 40 microm. Cellular growth was observed
      inside the scaffold and well-differentiated epithelium on top of it. CONCLUSION:
      To our knowledge, this is the first time three distinct scaffold types have been
      reported. All types supported the cell growth. The structure of the scaffolds
      affects the pattern of cell growth.

PMID- 17192729
TI  - Role of nitric oxide in urinary bladder function: effect of L-arginine.
AB  - BACKGROUND: Evidence indicates that decreased blood flow to the bladder plays a
      major role in obstructive bladder dysfunction in the rabbit model of partial
      bladder outlet obstruction (PBOO), and that nitric oxide (NO) regulation of blood
      flow may be important in modulating the degree of obstructive bladder
      dysfunction. The specific aim of our study is to determine the effect of feeding
      rabbits a diet high in L-arginine on the response to PBOO. MATERIALS AND METHODS:
      Sixteen male NZ White rabbits were separated into 4 groups of 4 each. The rabbits
      in groups 1 and 3 underwent PBOO. The rabbits in groups 2 and 4 were sham
      operated. For 1 week prior to surgery, and 2 weeks postoperatively, each rabbit
      in groups 1 and 2 was put on a diet containing 7% arginine. Rabbits in groups 3
      and 4 were on a normal diet (0.76% arginine). RESULTS: PBOO resulted in a greater
      increase in bladder weight in the control group than the arginine group. PBOO
      resulted in a greater decrease in compliance in the control group than the
      arginine group. The contractile responses to all agents in the arginine control
      group were greater than in the control normal diet group. PBOO resulted in a
      greater decrease in the response to field stimulation in the control group than
      in the arginine group. CONCLUSIONS: These studies clearly demonstrate that
      feeding rabbits a diet high in L-arginine was beneficial for the control rabbits,
      and reduced the level of dysfunctions following PBOO.

PMID- 17192730
TI  - Use of fibrin sealant in hypospadias surgical repair reduces the frequency of
      postoperative complications.
AB  - INTRODUCTION: Urethrocutaneous fistulas (UCF) and flap dehiscence (FD) are the
      most common postoperative complications after hypospadias (HS) surgical repair.
      The aim of this study was to evaluate whether the application of fibrin sealant
      over the site of surgery and suture lines reduces these complications. MATERIALS
      AND METHODS: A prospective cohort of consecutive patients was treated over a 3
      year period. 30 patients were submitted to HS surgical repair plus application of
      fibrin glue over the suture line and surgical site; for comparison, another 56
      subjects made up the control group which was submitted to surgical repair only.
      Variables assessed included: age, type of HS, fibrin sealant used, complications
      and number of surgical procedures required to treat recurrences. RESULTS: In
      general, the frequency of complications was 10 vs. 41% for UCF (p = 0.002), 13
      vs. 50% for FD (p = 0.001), and for flap necrosis (FN) 6.7 vs. 28.6% (p = 0.01)
      for the treatment and control groups respectively. The number of surgical
      reinterventions to treat recurrences was higher in the control group than in the
      study group (p = 0.04). CONCLUSION: The incidence of UCF after HS surgical repair
      can be reduced by applying fibrin sealant over the site of surgery and the suture
      lines.

PMID- 17192731
TI  - Pedicled rectus abdominis muscle flap wrapped around the penis for enhanced
      urethral pressure: an experimental study in dogs.
AB  - PURPOSE: It was the aim of this study to investigate the possibility of pedicled
      rectus abdominis muscle fascial flap wrapped around the penis for enhanced
      urethral pressure in dogs. MATERIALS AND METHODS: Ten adult male Beagle dogs
      underwent a procedure in which surrounding tissue of the penis at the site of the
      bulbomembranous urethra was dissected and a pedicled rectus abdominis muscle
      fascial flap was wrapped around the penis. Profilometry of the urethral pressure
      was carried out before, during and after the operation in all dogs. RESULTS:
      Before the operation, the mean maximal urethral pressure (MUP) was 48.9 +/- 11 cm
      H(2)O, and the mean MUP was 78.3 +/- 20.5 cm H(2)O after the penis was surrounded
      by a rectus muscle flap. There was a significant difference (t = 4.99, p =
      0.0007). Ten weeks after the operation, the mean MUP was 88.3 +/- 22.4 cm H(2)O,
      which was significantly higher than that before the operation (t = 6.0584, p =
      0.0002). CONCLUSIONS: A pedicled rectus abdominis muscle fascial flap wrapped
      around the penis can raise the urethral pressure. This provided an experiment
      basis for treating male urinary incontinence with a pedicled rectus muscle flap.

PMID- 17192732
TI  - Open surgical treatment of right-sided adrenal carcinomas >15 cm.
AB  - INTRODUCTION: Adrenal carcinomas are rare and are associated with a very poor
      prognosis. The incidence is estimated to be 1 in 1.7 million which represents
      0.02% of all cancers and 0.2% of all cancer mortality. The 5-year survival rate
      is 38%. The purpose of this paper is to present a single-institution experience
      in excising right-sided giant adrenal carcinomas, discussing the difficulties and
      the usage of special surgical devices to facilitate the procedure. PATIENTS AND
      METHODS: During June 2001 to June 2003, 18 patients with right-sided adrenal
      tumors were treated at the State University of Campinas Hospital--UNICAMP. 4 out
      of the 18 patients presented lesions >15 cm, representing the study group. The
      mean age was 37 (range 26-65) years, 3 patients were younger than 35 years, and 2
      patients were men. A right-sided extended subcostal incision was the surgical
      access in 1 patient (case 1) and a right-sided thoracoabdominal incision in the
      other 3 patients. RESULTS: Adrenal cortical carcinoma was the histological
      diagnosis according to the Weiss criteria; no positive surgical margin was
      detected, even in those patients with invasion of the hepatic capsule. The median
      follow-up period was 15 (range 6-30) months. CONCLUSIONS: A subcostal extended
      incision can accomplish broad exposure, if articulated costal retractors are
      available (used in liver transplantation), otherwise a thoracoabdominal incision
      is the best option. The most important feature of surgery is to accomplish an
      efficient hemostasis of the liver parenchyma. Suture and stitches are not
      suitable for minor vascular structures, and electrocauterization sometimes
      promotes hepatic lesions and does not provide bleeding control. Thus, the need
      for special hemostatic means is real, and they should be available in these
      situations.

PMID- 17192733
TI  - Prospective evaluation of samarium-153-EDTMP radionuclide treatment for bone
      metastases in patients with hormone-refractory prostate cancer.
AB  - PURPOSE: Bone is a common site of metastatic disease and the most frequent site
      of metastatic spread in patients with prostate cancer. Most patients with bone
      metastases complain of bone pains. This pain may be alleviated or eliminated by
      administration of radiotherapy at the site of metastases. Currently, two forms of
      radiotherapy administration exist: external-beam irradiation or intravenous
      administration of bone-seeking therapeutic radiopharmacon such as samarium-153
      ethylene-diamino-tetramethylene-phosphonate (EDTMP). This radiopharmacon produces
      beta-particles and concentrates in the areas of enhanced osteoblastic activity.
      The aim of this study was to assess the efficacy of (153)Sm-EDTMP therapy.
      MATERIALS AND METHODS: 32 men (aged 50-83, mean 70 years) with bone disseminated
      hormone-refractory prostate cancer and bone pain received (153)Sm-EDTMP. Mean
      applied dosage was 40 MBq/kg of the patient's body weight. Karnofsky performance
      status, pain score (numerical rating scale), analgesic score (WHO) and blood
      count were evaluated before, and 1 and 3 months after the treatment. RESULTS:
      Significant pain relief was observed in 44 and 38% of patients, mild relief in 31
      and 34% and no effect in 25 and 28% of patients, 1 and 3 months after
      administration, respectively. Pain palliation was accompanied by an improvement
      in mobility and a decrease in necessary dosage of analgesics. Mild and transient
      bone marrow suppression was observed as a side effect of (153)Sm-EDTMP treatment.
      None of the patients showed hematological toxicity grade 4, and only 2 showed
      grade 3 (NCI CTC). The majority of the patients had hematological toxicity grade
      1 or 2. CONCLUSION: After (153)Sm-EDTMP administration, bone pain palliation was
      observed in 72% of patients for 3 months. Hematological toxicity after (153)Sm
      EDTMP treatment was mild and transient.

PMID- 17192734
TI  - Percutaneous posterior tibial nerve stimulation in patients with chronic pelvic
      pain: a preliminary study.
AB  - BACKGROUND: We evaluated the clinical effect of intermittent percutaneous
      posterior tibial nerve stimulation (PTNS) in patients with chronic pelvic pain
      (CPP). METHODS: A total of 15 patients (10 women and 5 men, mean age 60.0 years,
      range 41-78) with CPP were enrolled in an open prospective clinical trial. The
      patients had 12 weekly outpatient treatment sessions, each lasting 30 min. All
      patients were evaluated by history, physical as well as urological examination,
      the Visual Analogue Scale (VAS) for pain and urgency, the International Prostate
      Symptom Score, and a 3-day frequency-volume chart. RESULTS: After 12 weeks of
      PTNS, 9 (60%) and 3 patients (30%) had an improvement of >50% and 25-50% in the
      VAS score for pain, respectively. Six patients (40%) ended up with a mean VAS <3.
      Mean VAS for pain changed from 8.1 +/- 0.2 at baseline to 4.1 +/- 0.6 after 12
      weeks of treatment (p < 0.01). Mean VAS for urgency changed from 4.5 +/- 1.0 at
      baseline to 2.7 +/- 0.7 after 12 weeks of treatment (p < 0.05). However, there
      was no statistically significant improvement in the International Prostate
      Symptom Score. There was no statistically significant difference in the number of
      voids and bladder volumes either. CONCLUSIONS: Our findings suggest that PTNS may
      improve pain symptoms for over half of the patients with CPP. Long-term follow-up
      studies are needed to verify these preliminary results.

PMID- 17192735
TI  - Impact of self-perceived bothersomeness on health-related quality of life in
      women with overactive bladder symptoms.
AB  - INTRODUCTION: The objective of this study was to examine the impact of self
      perceived bothersomeness of overactive bladder (OAB) symptoms on the health
      related quality of life (QOL). PATIENTS AND METHODS: A total of 92 women with a
      mean age of 53.3 (range 23-79) years suffering from OAB were included in the
      study. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and
      King's Health Questionnaire (KHQ) were used to assess the QOL. The patients were
      divided into two groups according to the bothersomeness degree of OAB: 'low' and
      'moderate' to 'high'. RESULTS: The SF-36 and the KHQ scores of the patients were
      significantly different from those of the controls (p <0.05), except for three
      domains of the SF-36. No difference in the results of the frequency-volume charts
      was observed between the two patient groups. The scores of the SF-36 and the KHQ
      domains did not correlate with the data of the frequency-volume charts.
      Significant differences were found between the two patient groups for most
      domains of the SF-36 (p <0.05). Significant differences were also detected in
      most domains of the KHQ (p <0.05). CONCLUSIONS: Objective data are not a
      sensitive tool for measuring the QOL in women with OAB symptoms. Our findings
      suggest that patient-perceived bothersomeness significantly influences QOL and
      that strategies for assessing bothersomeness should be developed to evaluate the
      QOL in these patients.

PMID- 17192736
TI  - Is fluoroscopy essential for retrieval of lower ureteric stones?
AB  - INTRODUCTION: The aim of this study was to assess the efficacy of ureteroscopy
      for lower ureteric stones without the use of fluoroscopy. PATIENTS AND METHODS:
      Between June 2001 and January 2005, a total of 110 patients with a mean age of
      33.5 years (range 12-65) suffering from of lower ureteral calculi (below the
      upper margin of the sacroiliac joint) prospectively underwent ureteroscopic
      removal. Retrograde pyelography was avoided, and no safety guidewire was placed.
      Whenever required, the ureteric meatus was dilated with a ureteric balloon under
      direct vision. Double-J stent placement was done with the aid of ureteroscopy. A
      fluoroscope was kept standby. The patients had a postoperative X-ray of the
      kidney-ureter-bladder region to document the stone clearance. RESULTS: The mean
      stone size was 8.7 mm (range 6-15). Complete clearance without the use of
      fluoroscopy was achieved in 99 patients (94.2%). Fluoroscopy was required in 6
      patients (4%) for calcified stricture (n = 1), duplex system (n = 1), narrow and
      tortuous meatus causing difficulty in passing the 5-Fr balloon dilator (n = 3),
      and confirmation of spontaneous passage of the stone (n = 1). Of the 13 patients
      who required balloon dilatation it was successfully achieved without fluoroscopy.
      Double-J stenting was done due to mucosal ulceration (n = 3), polypoid reaction
      (n = 2), and perforation (n = 1). All these patients had correct placement of the
      stent, as confirmed by X-ray of the kidney-ureter-bladder region postoperatively.
      CONCLUSIONS: To uphold the notion for radiation exposure to be as low as
      reasonably achievable, ureteroscopic stone retrieval can safely be done without
      the use of fluoroscopy in a significant number of patients.

PMID- 17192737
TI  - Acute scrotal pain in children--ten years' experience.
AB  - INTRODUCTION: Acute scrotal pain sometimes requires prompt surgical intervention
      and therefore accurate diagnosis of different etiologies of acute scrotal pain
      has great therapeutical and prognostic significance. The aim of this study was to
      analyze the incidence, symptomatology and results of treatment of acute scrotal
      pain in children. MATERIAL AND METHOD: The study included patients hospitalized
      at the Pediatric Surgery Clinic with a diagnosis of acute scrotal pain. We
      retrospectively analyzed anamnestic data (age of patient and duration of
      anamnesis prior to admission), clinical parameters obtained during physical
      examination, mode of treatment (operative or medical), intraoperative findings
      and (postoperative) treatment. RESULTS: The study included 256 patients with
      acute scrotal pain, aged from several hours up to 17 years of age (average 9.73
      years). The average duration of symptoms prior to admission was 56.74 h. Acute
      epididymitis was diagnosed in 110 patients (43.0%), torsion of the testicular
      appendage in 104 patients (40.6%), torsion of the testis in 30 patients (11.7%)
      and other pathologies in another 12 patients. 166 patients (64.8%) underwent
      surgery, 42 patients with orchiepididymitis (38.2%), 92 patients with torsion of
      the testicular appendage (88.5%), and 16.6% of the patients with other
      pathologies. 22 patients with torsion of the testis underwent surgery (73.3%),
      while the rest of the 8 patients underwent manual detorquation of the testis.
      CONCLUSION: Regardless of the etiology of the acute scrotal pain, it is of great
      importance that the patient seeks medical assistance promptly. It is therefore
      important to educate the parents and patients about the problems related to acute
      scrotal pain.

PMID- 17192738
TI  - Multiple intravesical instillations of low-dose resiniferatoxin in the treatment
      of refractory interstitial cystitis.
AB  - BACKGROUND: Current medications used in the treatment of interstitial cystitis
      (IC) have limited efficacy. This prospective study investigated the efficacy of
      multiple intravesical instillations of resiniferatoxin (RTX) at the concentration
      of 10 nM. METHODS: Patients with proven IC previously treated with traditional
      medications for more than 6 months without clinical benefit were enrolled. They
      were excluded if bladder outlet obstruction or urinary tract infection was
      present. Intravesical instillation of low-dose RTX (10 nM) once weekly for 4
      weeks was performed at the outpatient department. International Prostate Symptom
      Score (IPSS), 5-Point Pain Scale, and Quality of Life Index (QOL Index) were
      recorded. A videourodynamic study was done at baseline and 3 months after
      treatment. RESULTS: The therapeutic results and urodynamic parameters were
      compared between baseline and 3 months. Thirteen patients, including 10 women and
      3 men, were enrolled in this study. The mean duration of IC symptoms was 4.4 +/-
      2.5 years. The mean duration of active treatment was 15.3 +/- 8.6 months. One
      female patient dropped out due to severe bladder pain after RTX instillation.
      Among the 12 patients who completed the study treatment, subjective assessment
      revealed that 2 had an excellent therapeutic result, 5 had an improved result and
      5 remained unchanged from baseline. The overall satisfactory rate was 58.3%.
      IPSS, 5-Point Pain Scale, and QOL Index were significantly decreased after RTX
      treatment. There was no significant increase in mean functional bladder capacity
      or change in urodynamic parameters. No serious adverse event occurred after RTX
      treatment. CONCLUSIONS: This study suggests that multiple intravesical
      instillations of RTX at the concentration of 10 nM are effective in relieving
      lower urinary tract symptoms in patients with refractory IC. The treatment is
      tolerable and suitable for use on an outpatient clinic basis.

PMID- 17192739
TI  - Hyperbaric oxygen therapy attenuates renal ischemia/reperfusion injury in rats.
AB  - OBJECTIVE: Renal ischemia/reperfusion (I/R) injury occurs in both native and
      transplanted kidneys. Hyperbaric oxygen (HBO) has been shown to prevent I/R
      injury in different tissues. The aim of this study was to evaluate the effect of
      HBO on renal I/R injury in rats. MATERIALS AND METHODS: Sprague-Dawley rats were
      randomly assigned to one of three groups. The Control group (n = 6) received
      right nephrectomy. The I/R (n = 6) and I/R+HBO groups (n = 6) received 30 min
      left renal ischemia followed by 24 h of reperfusion after right nephrectomy. The
      I/R+HBO group (n = 6) received additional HBO therapy for 60 min at 2.5 absolute
      atmospheres starting at the initial 15th minute of reperfusion. RESULTS: In the
      I/R group, blood urea nitrogen (BUN) and creatinine levels increased
      significantly compared with the Control and I/R+HBO groups (p < 0.05). BUN and
      creatinine levels were similar in the Control and I/R+HBO groups. Kidney samples
      from I/R group rats revealed severe tubular damage and neutrophil infiltration at
      histopathological examination. The animals treated with HBO showed markedly
      improved lesions and less neutrophil infiltration compared with the I/R group (p
      < 0.05). CONCLUSIONS: HBO exhibited marked protection against I/R injury in this
      study as measured using BUN and creatinine levels and renal histopathology.
      However, further studies are needed to clarify the renoprotective effect of HBO
      on I/R injury.

PMID- 17192741
TI  - Female urethral duplication: an unusual condition.
AB  - We present the case of a 34-year-old woman who presented with a stone fragment
      stuck near her distal urethra without obstruction of her urinary flow. During an
      attempt to explore and remove the fragment, she was discovered to have complete
      urethral duplication with the stone stuck in one of two distal urethral orifices.
      This represents an extremely rare variant of a very unusual congenital anomaly,
      even more so as it occurs usually in male patients. Embryology, etiology, and
      clinical appearance of this rare anomaly are discussed.

PMID- 17192740
TI  - Late recurrence of a prostatic adenocarcinoma as a solitary splenic metastasis.
AB  - Splenic metastases of solid tumors are exceptional. We report the first case of
      an isolated splenic metastasis from prostate carcinoma, 5 years after radical
      prostatectomy. The splenic tumor was revealed by a pain and progressive increase
      in the serum prostate-specific antigen (PSA) level. Histology of the spleen
      showed an adenocarcinoma immunostained with cytokeratin and PSA markers. The
      patient remained asymptomatic and his serum PSA level was within normal limits 17
      months after the splenectomy. This case suggests that splenic metastasis might be
      the result of the growth of an early blood-borne micrometastasis within the
      spleen after a period of clinical latency.

PMID- 17192742
TI  - Giant renal calculus in a solitary functioning kidney.
AB  - We report a case of giant renal calculus 230 x 140 mm in size and weighing 1,350
      g in a solitary functioning kidney treated by nephrolithotomy. A 47-year-old man
      presented with right lumbar pain, abdominal mass and microscopic hematuria.
      Physical examination revealed a stony hard mass on the right side of the abdomen,
      extending from the subcostal region to the iliac crest. A giant renal calculus in
      his right kidney and atrophic nonfunctioning left kidney was diagnosed by
      ultrasonography, IVP and CT scan. Right nephrolithotomy was performed. Analysis
      revealed a calcium phosphate stone. This case is the largest and the heaviest
      stone reported in the literature in a solitary functioning kidney.

PMID- 17192744
TI  - The common cold. Facts about transmission and treatments.

PMID- 17192743
TI  - Aggressive fibromatosis in the urological system. Report of two adult patients
      and review of the literature.
AB  - Aggressive fibromatoses (AF) are locally aggressive neoplasms that do not
      metastasize but are frequently associated with one or more recurrences and
      subsequent associated morbidity. AF in the urological system is quite rare and
      has mainly been described in single case reports or as isolated cases in a large
      series of extra-abdominal desmoid tumors. We report 2 cases of AF in the bladder
      and scrotum, and provide a review of similar published cases.

PMID- 17192745
TI  - Prenatal exposure to DES may increase breast cancer risk.

PMID- 17192746
TI  - Studies show alternative therapies not very effective for menopause symptoms.

PMID- 17192747
TI  - Improving the outcome of stroke. Time is of the essence.

PMID- 17192748
TI  - Mayo Clinic office visit. Recent developments, future goals. An interview with
      Julie Abbott, M.D.

PMID- 17192749
TI  - Emotions after heart attack. An important part of healing.

PMID- 17192750
TI  - I've heard about serotonin syndrome in the news lately. Can you explain what this
      is?

PMID- 17192751
TI  - Are blood pressure machines in drugstores and shopping malls accurate?

PMID- 17192752
TI  - Diastolic dysfunction. Understanding a common cause of heart failure.

PMID- 17192753
TI  - Study supports use of statin drugs to prevent stroke recurrence.

PMID- 17192754
TI  - Left-side radiation for early-stage breast cancer may impact heart health, but
      not heart-related death.

PMID- 17192755
TI  - Early-onset menopause. Managing its special challenges.

PMID- 17192756
TI  - Mayo Clinic office visit. Body mass index. An interview with Warren Thompson,
      M.D.

PMID- 17192757
TI  - Coffee. Is it good or bad for you?

PMID- 17192758
TI  - One on one. Why can't I find Sudafed and other similar cold medications on
      drugstore shelves anymore?

PMID- 17192759
TI  - One on one. My older sister says she's been diagnosed with epilepsy, but she's
      never had any seizures. Is this possible?

PMID- 17192760
TI  - Mind and muscle: the cognitive-affective neuroscience of exercise.
AB  - There is growing basic-science interest in the mechanisms underpinning the
      positive effects of exercise on brain function and cognitive-affective
      performance. There is also increasing clinical evidence that exercise may prevent
      and treat various neuropsychiatric disorders. At the same time, there is growing
      awareness that athletic performance is mediated in crucial ways by central
      nervous system mechanisms. The relevant mechanisms in all these cases requires
      further exploration, but likely includes neurotrophic, neuroendocrine, and
      neurotransmitter systems, which in turn are crucial mediators of psychopathology
      and resilience. The hypothesis that Homo sapiens evolved as a specialist
      endurance runner provides an intriguing context against which to research the
      proximal mechanisms relevant to a cognitive-affective neuroscience of exercise.

PMID- 17192761
TI  - Effects of a tyramine-enriched meal on blood pressure response in healthy male
      volunteers treated with selegiline transdermal system 6 mg/24 hour.
AB  - BACKGROUND: Monoamine oxidase inhibitors are well recognized as effective
      antidepressant agents but are rarely used due, in part, to the risk of
      hypertensive crisis following the ingestion of foods high in tyramine ("cheese
      reaction"). A selegiline transdermal system (STS) was developed to provide
      antidepressant concentrations of selegiline in the brain, while preserving the
      gastrointestinal monoamine oxidase A (MAO-A) barrier. The present study was
      conducted to determine the effect of the STS 6 mg/24 hour on cardiovascular
      safety following the ingestion of approximately 400 mg of tyramine consumed as a
      component of aged cheeses. METHODS: In this open-label, single-center phase I
      study, cardiovascular vital signs were recorded following tyramine challenges
      during placebo and STS 6 mg/24 hr treatment. Subjects were observed for clinical
      signs and symptoms of a pressor response and/or potential hypertensive crisis
      during and following the challenges. RESULTS: Ingestion of tyramine-enriched
      meals following 13 consecutive days of treatment with the STS 6 mg/24 hr
      (pharmacokinetic steady-state) produced no clinically significant changes in
      cardiovascular vital signs in 12 healthy adult male subjects. No evidence of a
      tyramine pressor effect on systolic blood pressure or evidence of hypertensive
      crisis occurred during the STS treatment. CONCLUSION: These results suggest that
      STS 6 mg/24 hr may be administered without concern for dietary tyramine
      consumption.

PMID- 17192762
TI  - Hyperperfusion syndromes: insight into the pathophysiology and treatment of
      hypertensive encephalopathy.
AB  - Hypertensive encephalopathy is one of the manifestations of a hypertensive
      crisis. It is not the absolute value of the blood pressure that causes the
      encephalopathy, rather the presence of an abrupt rise in pressure. In terms of
      clinical and radiographic findings, there are many similarities among a group of
      entities, including hypertensive encephalopathy, eclampsia, and immunosuppressant
      neurotoxicity. Hyperperfusion syndromes may represent these clinical disease
      states that may share the same pathophysiology. Magnetic resonance imaging fluid
      attenuated inversion recovery sequences have recognized the prominent cortical
      involvement of the disease that had been previously missed on computed
      tomography. Studies have found cortical involvement in 94% of their patients,
      particularly in mild cases. Animal models demonstrate endothelial damage and
      enhanced pinocytosis in the cortex as reasons why edema may begin in that region
      of the brain. Patients diagnosed with hypertensive encephalopathy should be
      diagnosed and treated promptly in order to avoid further neurological
      complications. The mean arterial pressure should be lowered by 20% to 25% within
      the first hour of patient presentation, followed by further gradual reduction in
      blood pressure over the following 24 hours. Hypertensive emergency in acute
      ischemic stroke should be managed with more caution. According to the 2003
      American Stroke Association treatment guidelines, for patients with ischemic
      stroke not eligible for thrombolytic therapy, target blood pressures are a
      diastolic blood pressure <120 mmHg and systolic blood pressure <220 mmHg. The
      systolic pressure must be <185 mmHg and diastolic pressure <110 mmHg at all times
      if eligible for thrombolytic therapy.

PMID- 17192763
TI  - The switching of risperidone to olanzapine in elderly nursing-home patients with
      dementia: a retrospective study.
AB  - BACKGROUND: The behavioral and psychological symptoms of dementia present a major
      challenge in the management of these patients. There is no Food and Drug
      Administration-indicated medication for the management of these symptoms. Even
      though atypical antipsychotics are considered safer than conventional
      antipsychotics, safety concerns have emerged. INTRODUCTION: The FDA has issued
      warnings regarding the cardiac and metabolic side effects, cerebrovascular
      events, and, most recently, mortality risk. This study was conducted in 2003 when
      physicians were notified of the cerebrovascular risks of risperidone. Since then,
      similar warnings have been issued for olanzapine and aripiprazole. METHODS: The
      medical records of 58 elderly dementia patients who were taking risperidone and
      were abruptly switched to olanzapine were reviewed. Clinical Global Impressions
      scale at assigned retrospectively at switch, and weeks 4-6 assessed treatment.
      RESULTS: Baseline and follow-up Clinical Global Impressions scale scores were
      essentially unchanged. Adverse events were mild to moderate in severity. Mean
      risperidone dose at switch was 1.54 mg/day (range: 0.25-6 mg/day). Mean
      olanzapine dose after the switch was 5.69 mg/day (range: 2.52-27.5 mg/day).
      CONCLUSION: Most of the 58 patients were switched from risperidone to olanzapine
      without any deterioration in their clinical status. Even though it is generally
      not recommended in elderly patients, abrupt switching did not have any negative
      consequences in this group of patients.

PMID- 17192764
TI  - Clinical perspectives on the combination of D-cycloserine and cognitive
      behavioral therapy for the treatment of anxiety disorders.
AB  - In a particular success for translational research agendas, characterization of
      the neuronal circuits underlying fear extinction, and basic research in animal
      extinction paradigms, has led to intervention studies examining the use of D
      cycloserine (DCS) to enhance therapeutic learning from exposure-based cognitive
      behavioral therapy (CBT). In this article, we review these intervention studies,
      and discuss DCS augmentation of CBT relative to more traditional combination
      treatment strategies in the treatment of anxiety disorders. We offer an
      accounting, based on evidence for internal context effects, of current
      limitations in the combination of antidepressant or benzodiazepine medications
      with CBT and discuss the advantages of isolated-dosing strategies with DCS
      relative to these limitations. This strategy is contrasted with the chronic
      dosing applications of DCS for schizophrenia and Alzheimer's disease, and future
      directions for isolated-dosing strategies are discussed.

PMID- 17192765
TI  - Coenzyme Q10: a review of its promise as a neuroprotectant.
AB  - Coenzyme Q10 (CoQ10) is a powerful antioxidant that buffers the potential adverse
      consequences of free radicals produced during oxidative phosphorylation in the
      inner mitochondrial membrane. Oxidative stress, resulting in glutathione loss and
      oxidative DNA and protein damage, has been implicated in many neurodegenerative
      disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's
      disease. Experimental studies in animal models suggest that CoQ10 may protect
      against neuronal damage that is produced by ischemia, atherosclerosis and toxic
      injury. Though most have tended to be pilot studies, there are published
      preliminary clinical trials showing that CoQ10 may offer promise in many brain
      disorders. For example, a 16-month randomized, placebo-controlled pilot trial in
      80 subjects with mild Parkinson's disease found significant benefits for oral
      CoQ10 1,200 mg/day to slow functional deterioration. However, to date, there are
      no published clinical trials of CoQ10 in Alzheimer's disease. Available data
      suggests that oral CoQ10 seems to be relatively safe and tolerated across the
      range of 300-2,400 mg/day. Randomized controlled trials are warranted to confirm
      CoQ10's safety and promise as a clinically effective neuroprotectant.

PMID- 17192766
TI  - The pathogenesis of Alzheimer's disease and the role of Abeta42.

PMID- 17192767
TI  - Genetic polymorphisms in the ABCB1 gene and the effects of fentanyl in Koreans.
AB  - P-glycoprotein (PGP) is a polymorphic transporter encoded by the ABCB1 gene that
      contributes to the access of xenobiotics into the brain. There is no report on
      associations between genetic polymorphisms in ABCB1 and the clinical effects of
      fentanyl, although fentanyl may be a substrate of PGP. One hundred and twenty-six
      (126) unrelated Korean patients under spinal anesthesia with intravenous fentanyl
      (2.5 microg/kg) were recruited. Clinical effects (bispectral index, respiration
      rate, and need for oxygen supplementation) were monitored and these were compared
      between genotypes for three single nucleotide polymorphisms in ABCB1 (1236C>T,
      2677G>T/A, and 3435C>T). The allele and genotype frequencies were similar to
      previous data from Asians; the three major haplotypes, TTT (30%), TGC (24%), and
      CGC (24%) were expected among nine known haplotypes. During the initial 10 min,
      there were differences in suppression of respiration rate by fentanyl among the
      three genotypes (P=0.0933 for 1236C>T; P=0.0941 for 2677G>A/T; P=0.0013 for
      3435C>T, repeated-measures analysis of variance), but the differences in
      bispectral index among genotypes were not observed. Furthermore, patients
      carrying the linked 3435T and 2677T alleles showed a significant difference in
      the level of respiratory suppression (P=0.0056); those with genotypes susceptible
      to fentanyl (1236TT, 2677TT, and 3435TT) showed early (2-3 min) and profound
      suppression of respiration (65-73% of initial respiration rate) compared with
      other resistant genotypes (83-85% of initial respiration rate in 1236CC, 2677GG,
      and 3435CC). Although the need to supply oxygen was not significantly different
      between genotypes, there was a trend for increased demand by patients carrying
      both 1236T and 3435T alleles (P=0.0847). In conclusion, our results confirm ABCB1
      genotype data for Koreans and suggest that analysis of ABCB1 polymorphisms may
      have clinical relevance to prevent respiratory suppression by intravenous
      fentanyl or to anticipate its clinical effects.

PMID- 17192768
TI  - Depo-medroxyprogesterone in women on antiretroviral therapy: effective
      contraception and lack of clinically significant interactions.
AB  - We conducted an open-label, steady-state pharmacokinetic (PK) study of drug
      interactions among HIV-infected women treated with depo-medroxyprogesterone
      acetate (DMPA) while on nucleoside analogues plus nelfinavir (N=21), efavirenz
      (N=17), or nevirapine (N=16); or nucleosides only or no antiretroviral therapy as
      a control group (N=16). PK parameters were estimated using non-compartmental
      analysis, with between-group comparisons of medroxyprogesterone acetate (MPA) PKs
      and within-subject comparisons of ARV PKs before and 4 weeks after DMPA dosing.
      Plasma progesterone levels were measured at baseline and at 2, 4, 6, 8, 10, and
      12 weeks after DMPA dosing. There were no significant changes in MPA area under
      the concentration curve, peak or trough concentrations, or apparent clearance in
      the nelfinavir, efavirenz, or nevirapine groups compared to the control group.
      Minor changes in nelfinavir and nevirapine drug exposure were seen after DMPA,
      but were not considered clinically significant. Suppression of ovulation was
      maintained.

PMID- 17192769
TI  - CYP3A5 genotype markedly influences the pharmacokinetics of tacrolimus and
      sirolimus in kidney transplant recipients.
AB  - It is currently not clear whether the concentration-time curves of the
      immunosuppressants differ with respect to the CYP3A5, MDR1, or MRP2 genotype in
      dose-adapted stable kidney transplant patients. Dose/trough concentration ratios
      were obtained in 134 tacrolimus and 20 sirolimus-treated patients, and plasma
      concentration-time profiles were obtained from 16 (tacrolimus) and 10 (sirolimus)
      patients. Genotyping was carried out for CYP3A5 6986A>G; ABCB1 2677G>T/A, 3435C>T
      and ABCC2 -24C>T; 1249G>A; 3972C>T. Dose/trough concentration ratios were 0.67+/
      0.3 and 1.36+/-0.73 x 10(3) l (P<0.00001) for tacrolimus and 0.42+/-0.17 and
      0.84+/-0.46 x 10(3) l (P=0.18) for sirolimus in CYP3A5 non-expressors and
      expressors. The unadjusted tacrolimus area under curve (AUC)(0-12) was 106.8+/
      17.5 ng/ml x h compared with 133.3+/-42.2 ng/ml x h (P=0.37) without affecting
      serum creatinine. Mean unadjusted AUC(0-24) of sirolimus did not differ
      significantly either. Therefore, CYP3A5 expressor status and not transporter
      variants is a main determinant of oral clearance, particularly for tacrolimus.
      Dose adaptation according to trough levels, however, appears to be sufficient to
      maintain similar concentration-time profiles.

PMID- 17192771
TI  - Clinical pharmacology of 1,4-butanediol and gamma-hydroxybutyrate after oral 1,4
      butanediol administration to healthy volunteers.
AB  - 1,4-Butanediol (BD) is converted to gamma-hydroxybutyrate (GHB) after ingestion,
      and is associated with cases of dependence, coma, and death. The pharmacology of
      BD after oral ingestion has not been described in humans. Eight healthy
      volunteers (five men) were administered 25 mg/kg BD in a single oral dose after
      an overnight fast in a double-blinded, placebo-controlled, crossover study. Vital
      signs were monitored, and serial blood samples collected over 24 h for gas
      chromatography-mass spectrometry analysis of BD and GHB levels. Subjective mood
      and symptoms responses were assessed by visual analog scale. All subjects
      completed the study without significant adverse effects. BD was quickly absorbed
      and cleared, with time to maximal plasma concentration of 24+/-12 min, and
      elimination half-life (T(1/2)) of 39.3+/-11 min. BD was extensively converted to
      GHB, with a mean maximum GHB concentration of 45.6+/-19.7 mg/l reached 39.4+/
      11.2 min after BD ingestion. GHB T(1/2) averaged 32.3+/-6.6 min. Some subjects
      exhibited slow oral clearance of BD, which tended to correlate with a variant
      haplotype of the alcohol dehydrogenase gene ADH-IB G143A. Mean CL/F was 151.5+/
      176.5 ml/min kg for four subjects with variant haplotype versus 598.8+/-446.6
      ml/min kg for four wild-type subjects (P=0.061). Subjects reported feeling less
      awake and alert, less able to concentrate, and more lightheaded in the first 90
      min after BD ingestion. Pulse oximetry readings were lower 45 min after BD dosing
      with a mean oxygen saturation of 98.5% with BD versus 99.6% with placebo
      (P=0.031). Transient increases in mean systolic and diastolic blood pressure were
      observed, but other vital signs remained unchanged. BD was extensively converted
      to GHB after oral administration, but significant inter-individual variability in
      the rate of metabolism, possibly related to variants in ADH-IB, was observed. At
      the modest dose studied, significant clinical effects were not seen.

PMID- 17192770
TI  - effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin
      in healthy volunteers.
AB  - The inhibition of hepatic uptake transporters, such as OATP1B1, on the
      pharmacokinetics of atorvastatin is unknown. Here, we investigate the effect of a
      model hepatic transporter inhibitor, rifampin, on the kinetics of atorvastatin
      and its metabolites in humans. The inhibitory effect of a single rifampin dose on
      atorvastatin kinetics was studied in 11 healthy volunteers in a randomized,
      crossover study. Each subject received two 40-mg doses of atorvastatin, one on
      study day 1 and one on study day 8, separated by 1 week. One intravenous 30-min
      infusion of 600 mg rifampin was administered to each subject on either study day
      1 or study day 8. Plasma concentrations of atorvastatin and metabolites were
      above the limits of quantitation for up to 24 h after dosing. Rifampin
      significantly increased the total area under the plasma concentration-time curve
      (AUC) of atorvastatin acid by 6.8+/-2.4-fold and that of 2-hydroxy-atorvastatin
      acid and 4-hydroxy-atorvastatin acid by 6.8+/-2.5- and 3.9+/-2.4-fold,
      respectively. The AUC values of the lactone forms of atorvastatin, 2-hydroxy
      atorvastatin and 4-hydroxy-atorvastatin, were also significantly increased, but
      to a lower extent. An intravenous dose of rifampin substantially increased the
      plasma concentrations of atorvastatin and its acid and lactone metabolites. The
      data confirm that OATP1B transporters represent the major hepatic uptake systems
      for atorvastatin and its active metabolites. Inhibition of hepatic uptake may
      have consequences for efficacy and toxicity of drugs like atorvastatin that are
      mainly eliminated by the hepatobiliary system.

PMID- 17192772
TI  - VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction
      between both genotypes affects dose requirement.
AB  - In a prospective follow-up study of the effects of VKORC1 and CYP2C9 genotypes on
      the anticoagulation status of patients, we assessed the CYP2C9 and the VKORC1
      C1173T genotypes of patients during the initial 6 months of phenprocoumon
      treatment. We used linear regression models and Cox proportional hazard models to
      determine the effects of the VKORC1 and CYP2C9 genotypes on phenprocoumon dose
      requirements, overanticoagulation, and time to achieve stability. Allele
      frequencies of interest within the cohort (N=281) were 40.8% VKORC1 T-1173, 12.8%
      CYP2C9*2, and 6.9% CYP2C9*3. In patients with the VKORC1 CC genotype, carriers of
      a CYP2C9 polymorphism needed dosages that were nearly 30% lower than those for
      CYP2C9*1/*1 patients (P<0.001). In patients with a VKORC1 polymorphism,
      differences between carriers of a CYP2C9 polymorphism and CYP2C9*1/*1 were far
      smaller and largely not statistically significant. A larger part of the
      variability in dose requirement was explained by the VKORC1 genotype than by the
      CYP2C9 genotype (28.7% and 7.2%, respectively). Carriers of a combination of a
      CYP2C9 polymorphism and a VKORC1 polymorphism had a strongly increased risk of
      severe overanticoagulation (hazard ratio (HR) 7.20, P=0.002). Only carriers of a
      CYP2C9*2 allele had a decreased chance to achieve stability compared to
      CYP2C9*1/*1 patients (HR 0.61, P=0.004). In conclusion, the VKORC1 genotype
      modifies the effect of the CYP2C9 genotype on phenprocoumon dose requirements. A
      combination of polymorphisms of both genotypes is associated with a strongly
      increased risk of overanticoagulation, whereas delayed stabilization is mainly
      associated with the CYP2C9 genotype.

PMID- 17192773
TI  - Anticholinergic drugs and physical function among frail elderly population.
AB  - Increasing evidence from experimental studies and human observations suggests
      that drugs with anticholinergic properties can cause physical and mental
      impairment. The aim of this study was to evaluate the relationship between the
      use of drugs with anticholinergic activity and measures of physical performance,
      muscle strength, and functional status in persons aged 80 years or older. Data
      are from baseline evaluation of 364 subjects enrolled in the ilSIRENTE study. The
      ilSIRENTE study is a prospective cohort study performed in the mountain community
      living in the Sirente geographic area (L'Aquila, Abruzzo) in Central Italy.
      Physical performance was assessed using the physical performance battery score
      (Short Physical Performance Battery), which is based on three timed tests: 4
      meter walking speed, balance, and chair stand tests. Muscle strength was measured
      by hand grip strength. We defined as anticholinergic drugs all medications for
      which serum anticholinergic activity was previously demonstrated. Analyses of
      covariance were performed to evaluate the relationship of anticholinergic drugs
      with physical function. In the unadjusted model, all the physical performance,
      muscle strength, and functional measures showed significant associations with the
      anticholinergic drug use. After adjustment for potential confounders (age,
      gender, smoking, physical activity level, cognitive performance score, living
      alone, body mass index, congestive heart failure, lung diseases, diabetes), these
      associations were weaker but still statistically significant (physical
      performance battery score: non-users anticholinergic drugs 6.9, SE 0.1, users
      anticholinergic drugs 6.1, SE 0.2, P=0.05; hand grip strength: non-users
      anticholinergic drugs 31.3 kg, SE 0.8, users anticholinergic drugs 28.8 kg, SE
      1.0, P=0.05; Activities of Daily Living scale score: non-users anticholinergic
      drugs 1.2, SE 0.1, users anticholinergic drugs 1.6, SE 0.1, P=0.03; Instrumental
      Activities of Daily Living scale score: non-users anticholinergic drugs 2.7, SE
      0.1, users anticholinergic drugs 3.4, SE 0.1, P<0.001). The use of medication
      with anticholinergic properties is common among community older subjects in
      Italy. Our results suggest that among old-old subjects the use of anticholinergic
      drugs is associated with impaired physical performance and functional status.

PMID- 17192774
TI  - [123I]-beta-CIT SPECT imaging shows reduced thalamus-hypothalamus serotonin
      transporter availability in 24 drug-free obsessive-compulsive checkers.
AB  - Numerous findings indicate alterations in brain serotonin systems in obsessive
      compulsive disorder (OCD). We investigated the in vivo availability of thalamus
      hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who
      displayed prominent behavioral checking compulsions (OC-checkers). Four hours
      after injection of [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
      ([(123)I]-beta-CIT), single photon emission computed tomography (SPECT) scans
      were performed in 24 medication-free non-depressed OC-checkers and 24 age- and
      gender-matched healthy controls. For quantification of brain serotonin
      transporter availability, a ratio of specific to non-displaceable [(123)I]-beta
      CIT brain binding was used (V''(3)=(thalamus and hypothalamus
      cerebellum)/cerebellum). Drug-free non-depressed OC-checkers showed an 18%
      reduced brain serotonin transporter availability in the thalamus and
      hypothalamus, as compared with healthy control subjects (1.38+/-0.19 vs 1.69+/
      0.21; p<0.001). There was a strong negative correlation between severity of OC
      symptomatology (Y-BOCS scores) and SERT availability (r=-0.80; p<0.001).
      Moreover, we found a significant positive correlation between illness duration
      and serotonin transporter availability (r=0.43; p<0.05). This first report of
      significantly reduced [(123)I]-beta-CIT binding in the thalamus-hypothalamus
      region in OC-checkers suggests reduced brain serotonin transporter availability,
      which is more pronounced with increased severity of OC symptomatology and short
      duration of illness. The results provide direct evidence for an involvement of
      the serotonergic system in the pathophysiology of OCD.

PMID- 17192775
TI  - Increased expression of 5-HT6 receptors in the rat dorsomedial striatum impairs
      instrumental learning.
AB  - A number of studies have shown that systemic 5-HT(6) receptor antagonists can
      improve learning and memory, but the mechanism for these observations is not
      known. As striatum normally expresses 5-HT(6) receptors abundantly and is
      important in consolidating stimulus-response learning, we used targeted gene
      delivery to further increase the expression of 5-HT(6) receptors in rat striatum
      and then examined learning. Increased 5-HT(6) expression had no effect on
      performance in the Morris water maze, a hippocampal-dependent learning paradigm,
      and did not alter the latency to approach or consume sucrose tablets. However,
      rats with increased 5-HT(6) expression failed to acquire a reward-based
      instrumental learning task, a striatum-dependent learning model, during 3 days of
      successive sessions as compared to sham surgery or GFP-expressing control rats.
      This behavioral deficit was observed in rats overexpressing 5-HT(6) receptors in
      the dorsomedial striatum, but not in rats with increased dorsocentral striatal
      expression. The 5-HT(6) receptor-associated deficit was reversed by
      administration of a 5-HT(6) antagonist, SB-258585, before each training session.
      When animals learned the instrumental learning task before gene transfer,
      increased 5-HT(6) receptor expression had no effect on long-term recall or
      performance of the task or on extinction of operant responding. Thus, 5-HT(6)
      receptor activity in rat striatum disrupts acquisition of new instrumental
      learning but does not impair memory or performance of reward-motivated behavior
      once established.

PMID- 17192776
TI  - Lessons in the genomic diversity of malaria.
AB  - Genome-wide characterization of Plasmodium falciparum genetic diversity
      represents an important step in malaria genetics. The organizational and
      collaborative efforts to reach this goal and the results on linkage
      disequilibrium and genetic diversity among worldwide isolates provide general
      lessons.

PMID- 17192778
TI  - Toward a malaria haplotype map.

PMID- 17192779
TI  - Following the herd.

PMID- 17192780
TI  - Sending out an SOS.

PMID- 17192781
TI  - Chaotic license for genetic instability and cancer.

PMID- 17192782
TI  - Telomeres, p21 and the cancer-aging hypothesis.

PMID- 17192785
TI  - Systematic meta-analyses of Alzheimer disease genetic association studies: the
      AlzGene database.
AB  - The past decade has witnessed hundreds of reports declaring or refuting genetic
      association with putative Alzheimer disease susceptibility genes. This wealth of
      information has become increasingly difficult to follow, much less interpret. We
      have created a publicly available, continuously updated database that
      comprehensively catalogs all genetic association studies in the field of
      Alzheimer disease (http://www.alzgene.org). We performed systematic meta-analyses
      for each polymorphism with available genotype data in at least three case-control
      samples. In addition to identifying the epsilon4 allele of APOE and related
      effects, we pinpointed over a dozen potential Alzheimer disease susceptibility
      genes (ACE, CHRNB2, CST3, ESR1, GAPDHS, IDE, MTHFR, NCSTN, PRNP, PSEN1, TF, TFAM
      and TNF) with statistically significant allelic summary odds ratios (ranging from
      1.11-1.38 for risk alleles and 0.92-0.67 for protective alleles). Our database
      provides a powerful tool for deciphering the genetics of Alzheimer disease, and
      it serves as a potential model for tracking the most viable gene candidates in
      other genetically complex diseases.

PMID- 17192787
TI  - Distribution and viral load of eight oncogenic types of human papillomavirus
      (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and
      carcinoma.
AB  - Current human papillomavirus (HPV) DNA testing using pooled probes, although
      sensitive, lacks specificity in predicting the risk of high-grade cervical
      intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV
      genotyping, viral load, and viral integration status as potential predictive
      markers for CIN progression, we performed HPV genotyping in formalin-fixed,
      paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs
      (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened
      using consensus primers GP5+/GP6+ and PGMY09/11. HPV genotyping and viral load
      measurement were performed using quantitative real-time PCR for eight oncogenic
      HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status
      was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA
      positivity increased in parallel with the severity of CINs and carcinoma, with
      59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P
      trend=0.004). The eight oncogenic HPV types were significantly associated with
      CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval
      (CI), 5.67-39.76; P<0.0001) compared with the unknown HPV types (OR, 2.87; 95%
      CI, 0.89-9.22; P=0.08). HPV 16 was the predominant oncogenic HPV type in CIN 2/3
      (51%) and carcinoma (71%) and integrated significantly more frequently in
      carcinoma than in CIN 2/3 (P=0.004). No significant differences in viral load
      were observed across the disease categories. Our findings suggest that selected
      genotyping for the eight oncogenic HPV types might be useful in separating women
      with a higher risk of CIN progression from those with a minimal risk. We also
      conclude that the HPV 16 integration status has potential to be a marker for risk
      assessment of CIN progression.

PMID- 17192788
TI  - IMP3 is a novel biomarker for adenocarcinoma in situ of the uterine cervix: an
      immunohistochemical study in comparison with p16(INK4a) expression.
AB  - Adenocarcinoma in situ of the uterine cervix remains a diagnostic challenge in a
      small proportion of cases. This suggests a need for biomarker that may be of help
      in establishing the diagnosis. The aim of this study was to evaluate the
      potential of insulin-like growth factor-II mRNA-binding protein 3 and cyclin
      dependent kinase inhibitor p16(INK4a) as biomarkers for adenocarcinoma in situ.
      Forty-four samples of adenocarcinoma in situ from 40 patients and 23 control
      cases of benign uterine cervix were included in this study. In addition to benign
      endocervical epithelium, 19 of these 23 control cases also showed focal tubal
      metaplasia. Cytoplasmic immunoreactivity for insulin-like growth factor-II mRNA
      binding protein 3 was identified in 41 (93%) adenocarcinoma in situ samples,
      among which, 29 (71%), 10 (24%), and 2 (5%) samples showed insulin-like growth
      factor-II mRNA-binding protein 3 positive staining in 50% or more, >5 to <50 and
      <5% of adenocarcinoma in situ lesional cells, respectively. Immunohistochemical
      reaction intensity for insulin-like growth factor-II mRNA-binding protein 3 was
      found to be strong in 34 adenocarcinoma in situ samples, intermediate in five,
      and weak in two. All 23 control cases were negative for insulin-like growth
      factor-II mRNA-binding protein 3. p16(INK4a) expression was identified in all of
      the adenocarcinoma in situ samples with intermediate staining intensity seen in
      seven samples and strong in the remainder. Fourteen of 19 (74%) tubal metaplasia
      cases showed p16(INK4a) immunoreactivity in >50% of the tubal metaplastic
      epithelium with staining intensity ranging from weak to strong. Our findings
      demonstrate significant expression of insulin-like growth factor-II mRNA-binding
      protein 3 and p16(INK4a) in adenocarcinoma in situ as compared to benign
      endocervical glands, suggesting that expression of these biomarkers may be
      helpful in the distinction of adenocarcinoma in situ from benign endocervical
      glands, particularly in difficult borderline cases.

PMID- 17192789
TI  - Histologic features are important prognostic indicators in early stages lung
      adenocarcinomas.
AB  - This study attempts to evaluate the clinicopathologic features of mixed subtype
      adenocarcinomas and the prognostic implications of histopathology
      classifications. Surgical specimens from 141 patients with clinical stage I or II
      lung adenocarcinoma during the period 1992-2004 were included. These cases were
      classified into four groups defined by the extent of the bronchioloalveolar
      carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed
      subtype with predominant bronchioloalveolar carcinoma component and < or = 5 mm
      invasive component; group III: mixed subtype with bronchioloalveolar carcinoma
      component and > 5 mm invasive component; group IV: invasive carcinoma with no
      bronchioloalveolar carcinoma component. Descriptive statistics were used to
      examine the groups with respect to age, tumor size, lymph node metastasis, and Ki
      67 and p53 expression levels. Death rate for the groups was obtained by patient's
      charts and from the National Death Index database. The population was similar in
      age, tumor size and lymph node metastasis. Immunohistochemical results showed
      that the mean Ki-67 labeling and the amount of p53 overexpression had the same
      trend of increasing mean values or positive results from groups I to IV. The
      reported proportion of deaths ranged from 0% for groups I and II, 20% in patients
      with predominant invasive component with bronchioloalveolar carcinoma (group
      III), and 18% in patients with invasive carcinomas and no bronchioloalveolar
      carcinoma component (group IV). The difference between the proportion of patients
      with reported deaths in the time period of this study in the combined greater
      than 5 mm+pure invasive groups (groups III, IV), and the < 5 mm + noninvasive
      groups (groups I, II) is statistically significant. These results suggest that
      histological features may be useful in defining categories of lung
      adenocarcinomas with differing survival and prognostic features. These results
      are helpful in defining a subcategory of 'minimally invasive adenocarcinoma',
      which has features similar to bronchioloalveolar carcinoma.

PMID- 17192790
TI  - Immunohistochemical detection of GLUT-1 can discriminate between reactive
      mesothelium and malignant mesothelioma.
AB  - The separation of benign reactive mesothelium (RM) from malignant mesothelial
      proliferation can be a major challenge. A number of markers have been proposed,
      including epithelial membrane antigen, p53 protein, and P-glycoprotein. To date,
      however, no immunohistochemical marker that allows unequivocal discrimination of
      RM from malignant pleural mesothelioma (MPM) has been available. A family of
      glucose transporter isoforms (GLUT), of which GLUT-1 is a member, facilitate the
      entry of glucose into cells. GLUT-1 is largely undetectable by
      immunohistochemistry in normal epithelial tissues and benign tumors, but is
      expressed in a variety of malignancies. Thus, the expression of GLUT-1 appears to
      be a potential marker of malignant transformation. Recently, in fact, some
      studies have shown that GLUT-1 expression is useful for distinguishing benign
      from malignant lesions. The purpose of the present study was to evaluate the
      diagnostic utility of GLUT-1 expression for diagnostic differentiation between RM
      and MPM. Immunohistochemical staining for GLUT-1 was performed in 40 cases of RM,
      48 cases of MPM, and 58 cases of lung carcinoma. Immunohistochemical GLUT-1
      expression was seen in 40 of 40 (100%) MPMs, and in all cases the expression was
      demonstrated by linear plasma membrane staining, sometimes with cytoplasmic
      staining in addition. GLUT-1 expression was also observed in 56 out of 58 (96.5%)
      lung carcinomas. On the other hand, no RM cases were positive for GLUT-1. GLUT-1
      is a sensitive and specific immunohistochemical marker enabling differential
      diagnosis of RM from MPM, whereas it cannot discriminate MPM from lung carcinoma.

PMID- 17192791
TI  - Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from
      various organs and clinicopathological analysis of MGB1-positive breast cancers.
AB  - Previously, we used the reverse transcription-polymerase chain reaction (RT-PCR)
      to show that mammaglobin (MGB1) can serve as a differential marker of breast
      cancer metastasis from primary lung cancer. However, mRNA-based methods are not
      appropriate for use in clinical practices. In this study, we examined MGB1
      protein expression in 480 tumors from various organs using immunohistochemical
      detection and a tissue microarray technique. Breast cancers expressing MGB1 were
      also analyzed clinicopathologically to determine whether these cancers constitute
      a characteristic subset. Immunohistochemically, MGB1 was expressed specifically
      in breast cancers. Of the other cancers examined, including 29 of the head and
      neck, eight of the thyroid, 106 of the lung, 35 of the gastrointestinal tract,
      three of the pancreas, 14 of the uterine cervix and 13 of the ovary, none were
      positive for MGB1 except a proportion of salivary gland tumors (6/11, 55%) and
      endometrial cancers (3/23, 13%). Among the 238 breast cancers, MGB1 was expressed
      in 114 (48%), most of which were classified histologically as invasive duct or
      lobular carcinomas. Clinicopathologically, MGB1 expression was associated with
      positive expression of estrogen receptors and negative expression of CK5, but not
      with pathological stage, HER2 gene amplification or p53 immunoreactivity. Kaplan
      Meier analysis revealed prolonged disease-free survival in patients with MGB1
      positive breast cancers (log rank test, P=0.016), but the Cox proportional hazard
      model failed to confirm that MGB1 was an independent prognostic factor (hazard
      ratio 1.77, P=0.1755). In terms of practical diagnosis, MGB1 immunohistochemistry
      can serve as a differential marker of breast cancer metastasis from primary lung
      cancer for two reasons. Firstly, HER2-positive breast cancer frequently lacks
      estrogen receptor expression, but MGB1 is expressed in about half of this
      subtype. Secondly, as primary lung adenocarcinomas may express estrogen
      receptors, MGB1 expression provides further discrimination of the origin of
      breast cancers.

PMID- 17192792
TI  - Amplifications of EGFR gene and protein expression of EGFR, Her-2/neu, c-kit, and
      androgen receptor in phyllodes tumor of the prostate.
AB  - Phyllodes tumor of the prostate is a rare neoplasm with an unpredictable clinical
      behavior. It may undergo early recurrence with sarcomatous transformation or may
      even metastasize. Because targeted therapies have shown great success against
      several malignancies, there is hope that these same therapies may show similar
      promise in the treatment of other neoplasms. This study was undertaken to
      investigate both amplification of the epidermal growth factor receptor (EGFR)
      gene by fluorescence in situ hybridization and the overexpression of EGFR, Her
      2/neu, CD117 (c-kit), and androgen receptor by immunohistochemical staining in a
      series of 11 phyllodes tumors of the prostate. In the stromal elements, EGFR gene
      amplification was present in four of 11 tumors and polysomy chromosome 7 was
      present in two of 11 tumors. No amplification was present in the epithelial
      components. Only one of 11 tumors had polysomy of chromosome 7 in the epithelial
      components. Immunohistochemically, in the stromal components, EGFR expression was
      demonstrable in four of 11 tumors and androgen receptor was demonstrated in six
      of 10 tumors. Neither Her-2/neu nor c-kit expression was seen in the stromal
      components of any of the 11 tumors. In the epithelial components, EGFR expression
      was present in all 11 tumors with strong staining in the basal cell layers and
      weak or no staining in luminal epithelium; androgen receptor expression was seen
      in seven of 10 tumors; Her-2/neu was weakly positive in four of 11 tumors; and c
      kit expression was present focally and weakly in two of 11 cases with only 2-5%
      of cells staining. The highest staining intensity and the highest percentage of
      positively staining cells were seen with EGFR immunostaining in both the stromal
      and epithelial (mainly basal cells) components. Androgen receptor staining showed
      the next highest staining intensity and percentage of positive cells in both
      components. Her-2/neu and c-kit were only weakly or infrequently expressed in the
      epithelial components of prostatic phyllodes tumors. Our data indicate that EGFR
      and androgen receptor are frequently and strongly expressed in both epithelial
      and stromal components of prostatic phyllodes tumors. EGFR gene amplification is
      frequently present in prostatic phyllodes tumors and may account for one of the
      mechanisms leading to protein overexpression in some but not all cases. Anti-EGFR
      and/or antiandrogen agents may be potentially useful for management of patients
      with tumors expressing EGFR and/or androgen receptor.

PMID- 17192793
TI  - Distribution of HPV genotypes in 282 women with cervical lesions: evidence for
      three categories of intraepithelial lesions based on morphology and HPV type.
AB  - Previously we found differences in the distribution of the individual human
      papillomavirus types in cervical cancers and high-grade squamous intraepithelial
      lesions. This suggested that there were differences in risk for progression of
      high-grade squamous intraepithelial lesions that were related to human
      papillomavirus type within the category of oncogenic genotypes. In this work, we
      add additional cases including low-grade squamous intraepithelial lesions.
      ThinPrep samples from 282 squamous intraepithelial lesions and invasive cervical
      cancers were categorized morphologically by consensus interpretation and
      genotyped for 27 individual human papillomavirus types by polymerase chain
      reaction-based reverse line blot analysis using PGMY09/PGMY11 consensus primers
      for the L1 open reading frame. The 27 human papillomavirus types were divided
      into three categories: high risk 16, 18, 31, 45; intermediate risk 33, 35, 39,
      51, 52, 56, 58, 59, 68, 73, 82, 83; and low risk: 6, 11, 26, 40, 42, 53, 54, 55,
      57, 66, and 84. Of the 282 cases of cancer and squamous intraepithelial lesions,
      95.7% were positive for one or more of 27 human papillomavirus types and 38.7%
      had two or more genotypes. Three major categories of squamous intraepithelial
      lesions were identified based upon the combination of consensus diagnosis and
      human papillomavirus category: (1) high-grade squamous intraepithelial lesions
      associated with high-risk human papillomavirus types that appear to be at
      increased risk for progression to carcinoma; (2) squamous intraepithelial lesions
      (typically low-grade intraepithelial lesions and high-grade lesions consistent
      with moderate dysplasia) associated with intermediate risk human papillomavirus
      types with limited or indeterminate risk for progression; (3) low-grade squamous
      intraepithelial lesions associated with low-risk human papillomavirus types with
      little or no risk for progression. Only a subset of human papillomavirus
      genotypes commonly considered to be oncogenic were closely associated with
      invasive cervical cancer and high-grade squamous intraepithelial lesions classed
      as severe dysplasia. Other oncogenic types were closely associated with high
      grade squamous intraepithelial lesions of moderate dysplasia and low-grade
      squamous intraepithelial lesions. This suggests that risk for progression to
      invasion in squamous intraepithelial lesions is closely related to human
      papillomavirus genotype. Knowledge of the associated human papillomavirus type in
      women with morphologic squamous intraepithelial lesions may help to clarify risk
      for progression.

PMID- 17192795
TI  - The suspension of treatments in ADAPT: concerns beyond the cardiovascular safety
      of celecoxib or naproxen.

PMID- 17192794
TI  - Rifampicin/Cotrimoxazole/Isoniazid versus mefloquine or quinine + sulfadoxine-
      pyrimethamine for malaria: a randomized trial.
AB  - OBJECTIVES: Previous studies of a fixed combination including cotrimoxazole,
      rifampicin, and isoniazid (Cotrifazid) showed efficacy against resistant strains
      of Plasmodium falciparum in animal models and in small-scale human studies. We
      conducted a multicentric noninferiority trial to assess the safety and efficacy
      of Cotrifazid against drug-resistant malaria in Papua New Guinea. DESIGN: The
      trial design was open-label, block-randomised, comparative, and multicentric.
      SETTING: The trial was conducted in four primary care health facilities, two in
      urban and two in rural areas of Madang and East Sepik Province, Papua New Guinea.
      PARTICIPANTS: Patients of all ages with recurrent uncomplicated malaria were
      included. INTERVENTIONS: Patients were randomly assigned to receive Cotrifazid,
      mefloquine, or the standard treatment of quinine with sulfadoxine-pyrimethamine
      (SP). OUTCOME MEASURES: Incidence of clinical and laboratory adverse events and
      rate of clinical and/or parasitological failure at day 14 were recorded. RESULTS:
      The safety analysis population included 123 patients assigned to Cotrifazid, 123
      to mefloquine, and 123 to quinine + SP. The Cotrifazid group experienced lower
      overall incidence of adverse events than the other groups. Among the efficacy
      analysis population (72 Cotrifazid, 71 mefloquine, and 75 quinine + SP), clinical
      failure rate (symptoms and parasite load) on day 14 was equivalent for the three
      groups (0% for Cotrifazid and mefloquine; 1% for quinine + SP), but
      parasitological failure rate (P. falciparum asexual blood-stage) was higher for
      Cotrifazid than for mefloquine or quinine + SP (9% [PCR corrected 8%] versus 0%
      and 3%, respectively [p = 0.02]). CONCLUSION: Despite what appears to be short
      term clinical equivalence, the notable parasitological failure at day 14 in both
      P. falciparum and P. vivax makes Cotrifazid in its current formulation and
      regimen a poor alternative combination therapy for malaria.

PMID- 17192796
TI  - Prostate biopsy: targeting cancer for detection and therapy.
AB  - Despite improvements in cancer detection, prostate biopsy still lacks the ability
      to accurately map locations of cancer within the prostate. Improvements in
      prostate imaging may allow more accurate mapping of overall disease volume.
      Magnetic resonance (MR) spectroscopy allows improved specificity in detecting
      even small foci of disease within the peripheral zone. Improvements in MR-guided
      biopsy techniques may allow this technology to be adapted to therapeutics as
      well. Computer modeling of individual prostates serves as a means of designing
      optimized plans for prostate biopsy. The use of novel targeted biopsy schemes may
      allow an integration of available technologies in detection and localization of
      prostate cancer. Computer-directed needle biopsies based on anatomic landmarks
      within the prostate and computerized three-dimensional reconstruction of the
      gland may allow a highly reproducible means of identifying small foci of cancer,
      targeting them for therapy, and monitoring for recurrence. The TargetScan(R)
      system (Envisioneering Medical Technologies, St. Louis, MO) is the first
      technology to integrate available targeting methodologies in a systematic
      fashion.

PMID- 17192797
TI  - The role of gonadotropin-releasing hormone antagonists for the treatment of
      benign prostatic hyperplasia.
AB  - Medical therapy is the preferred first-line approach in the management of lower
      urinary tract symptoms in men with benign prostatic hyperplasia. The magnitude of
      the improvement in lower urinary tract symptoms observed in response to
      combination therapy (alpha-blocker plus 5-alpha reductase inhibitors) does not
      approach that achieved with prostatectomy. Various drugs have been under
      consideration, including BXL628, lonidamine, and phosphodiesterase inhibitors,
      all of which have had unacceptable side effects. The gonadotropin-releasing
      hormone antagonist cetrorelix is associated with dose-dependent symptom
      improvement and reduction of prostate volume. Elucidating the mechanism for
      cetrorelix-mediated improvement in lower urinary tract symptoms will likely
      contribute to unraveling the pathophysiology of lower urinary tract symptoms in
      men.

PMID- 17192798
TI  - Diagnostic Utility of the ImmunoCyt/uCyt+ Test in Bladder Cancer.
AB  - Bladder cancer is a common malignancy in the United States. Although urine
      cytology is a useful adjunct in both diagnosis and follow-up and is highly
      sensitive for detecting high-grade tumors, it is limited by decreased sensitivity
      in detecting low-grade tumors, which constitute the majority of new diagnoses.
      Additional screening tests with high sensitivity and specificity for urothelial
      tumors of all grades are indicated to help improve the diagnostic ability of
      urine cytology as well as to reduce the need for frequent cystoscopies,
      especially in those with low-risk disease. Several assays have been developed,
      with the ImmunoCyt/uCyt+ test (DiagnoCure, Inc., Quebec, Canada) being especially
      promising. Recent studies on the applicability and efficacy of ImmunoCyt/uCyt+
      testing are reviewed, as are its sensitivity, specificity, and predictive value
      in the follow-up and screening of urothelial malignancies.

PMID- 17192799
TI  - Botulinum toxin for the treatment of idiopathic and neurogenic overactive
      bladder: state of the art.
AB  - The pharmacologic treatment of overactive bladder and detrusor overactivity,
      whether idiopathic or neurogenic, has centered around blocking muscarinic
      receptors on the detrusor muscle. Although newer agents have been developed with
      better tolerability and safety, the basic mechanism by which the "irritable"
      detrusor is treated has not changed in decades. Although effective in many cases
      of idiopathic and neurogenic detrusor overactivity and overactive bladder,
      antimuscarinic agents fall short in many other cases because of lack of efficacy
      and/or tolerability. For the past several years, there has been increasing
      evidence to support the use of botulinum toxin for the treatment of detrusor
      overactivity and overactive bladder syndrome not effectively treated by
      anticholinergics. From early open-label studies to the more recent randomized,
      controlled trials, efficacy and tolerability data have been very encouraging.
      Botulinum toxin is not yet approved by the US Food and Drug Administration for
      the treatment of detrusor overactivity and overactive bladder, but the positive
      results seen thus far cannot be ignored.

PMID- 17192800
TI  - Penile rehabilitation after radical prostatectomy: important therapy or wishful
      thinking?
AB  - On the basis of data accumulated thus far, it is reasonable to discuss the
      implementation of a "penile rehabilitation" program with patients undergoing
      radical prostatectomy. Central to discussions of penile rehabilitation after
      radical prostatectomy is evidence demonstrating significant fibrotic changes in
      the corpus cavernosum that occur postoperatively. Several studies have been
      published evaluating the efficacy of various pro-erectogenic agents. The limited
      data regarding intracavernous injections and vacuum constriction devices suggest
      that an increased percentage of treated patients experienced a return of natural
      erections compared with patients who received no treatment. Longer, prospective,
      randomized, placebo-controlled studies will be needed to confirm the utility of
      these treatments. Data from contemporary studies evaluating the chronic use of
      oral phosphodiesterase type 5 inhibitors suggest a beneficial effect on
      endothelial cell function among men suffering from erectile dysfunction due to a
      variety of causes. Limited data suggest that this effect might be seen among post
      prostatectomy patients, implying a possible role for these agents in enhancing
      the return of sexual function in such individuals.

PMID- 17192801
TI  - Advances in the treatment of lower urinary tract symptoms and benign prostatic
      hyperplasia: highlights from the 21st European association of urology congress,
      april 5-8, 2006, paris, france.

PMID- 17192802
TI  - Robotic ureterolysis, retroperitoneal biopsy, and omental wrap for the treatment
      of ureteral obstruction due to idiopathic retroperitoneal fibrosis.
AB  - Retroperitoneal fibrosis (RPF) is a rare disorder of unclear etiology
      characterized by chronic inflammation of the retroperitoneum, which can involve
      any of the retroperitoneal structures, most notably the ureters, aorta, and vena
      cava. Historically, open biopsy, ureterolysis, and transpositioning or omental
      wrapping of the involved ureter(s) have been the preferred surgical treatments of
      RPF, with success rates greater than 90%. More recently, successful laparoscopic
      biopsy, ureterolysis, and ureteral omental wrapping and intraperi-tonealization
      have been described. We report the first case in the literature of idiopathic RPF
      managed with robotic ureterolysis and laparoscopic omental ureteral wrapping.

PMID- 17192803
TI  - The risk of retractile testes becoming ascending testes.

PMID- 17192804
TI  - Conflicting insights into the role of watchful waiting in the management of
      adenocarcinoma of the prostate.

PMID- 17192805
TI  - Health care usage, botulinum toxin for overactive bladder.

PMID- 17192806
TI  - Fertility.

PMID- 17192807
TI  - Hormetic effects on longevity of hydrogen peroxide in Drosophila melanogaster
      flies living on a poorly nutritious medium.
AB  - Subjecting flies to a mild stress at a young age may increase longevity and
      protect against strong stresses occurring at middle age. The purpose of this
      article is to test whether a mild stress could also increase survival time of
      flies living in stressful conditions. Flies were transferred at middle age in
      vials where they could only feed on a saccharose solution without any other
      nutrient. This poor medium is known to decrease longevity and it was hypothetized
      that adding hydrogen peroxide to it could minimize this negative effect. While
      high doses of hydrogen peroxide decreased further longevity, a low dose increased
      it in 4-week-old males and, only in some experiments, in females. This low dose
      had however not any positive effect on behavioral aging, resistance to heat and
      starvation. The positive effect of hydrogen peroxide appeared not to be due to a
      sanitary action upon the environment. Rather, it seems that hydrogen peroxide was
      a mild stress helping flies to cope with the negative effects of saccharose on
      longevity. Therefore, it is concluded that hydrogen peroxide, beyond the
      deleterious effects of high doses, could have positive effects in organisms when
      used at a low dose, particularly in stressful living conditions.

PMID- 17192808
TI  - Current topics in genome evolution: molecular mechanisms of new gene formation.
AB  - Comparative genome analyses reveal that most functional domains of human genes
      have homologs in widely divergent species. These shared functional domains,
      however, are differentially shuffled among evolutionary lineages to produce an
      increasing number of domain architectures. Combined with duplication and adaptive
      evolution, domain shuffling is responsible for the great phenotypic complexity of
      higher eukaryotes. Although the domain-shuffling hypothesis is generally
      accepted, determining the molecular mechanisms that lead to domain shuffling and
      novel gene creation has been challenging, as sequence features accompanying the
      formation of known genes have been obscured by accumulated mutations. The growing
      availability of genome sequences and EST databases allows us to study the
      characteristics of newly emerged genes. Here we review recent genome-wide DNA and
      EST analyses, and discuss the three major molecular mechanisms of gene formation:
      (1) atypical spicing, both within and between genes, followed by adaptation, (2)
      tandem and interspersed segmental duplications, and (3) retrotransposition
      events.

PMID- 17192810
TI  - Legionella pneumophila - a human pathogen that co-evolved with fresh water
      protozoa.
AB  - The bacterial pathogen Legionella pneumophila is found ubiquitously in fresh
      water environments where it replicates within protozoan hosts. When inhaled by
      humans it can replicate within alveolar macrophages and cause a severe pneumonia,
      Legionnaires disease. Yet much needs to be learned regarding the mechanisms that
      allow Legionella to modulate host functions to its advantage and the regulatory
      network governing its intracellular life cycle. The establishment and publication
      of the complete genome sequences of three clinical L. pneumophila isolates paved
      the way for major breakthroughs in understanding the biology of L. pneumophila.
      Based on sequence analysis many new putative virulence factors have been
      identified foremost among them eukaryotic-like proteins that may be implicated in
      many different steps of the Legionella life cycle. This review summarizes what is
      currently known about regulation of the Legionella life cycle and gives insight
      in the Legionella-specific features as deduced from genome analysis.

PMID- 17192809
TI  - Autotaxin (NPP-2) in the brain: cell type-specific expression and regulation
      during development and after neurotrauma.
AB  - Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with
      lysophospholipase D activity that generates bioactive lysophosphatidic acid.
      Lysophosphatidic acid has been implicated in various neural cell functions such
      as neurite remodeling, demyelination, survival and inhibition of axon growth.
      Here, we report on the in vivo expression of autotaxin in the brain during
      development and following neurotrauma. We found that autotaxin is expressed in
      the proliferating subventricular and choroid plexus epithelium during embryonic
      development. After birth, autotaxin is mainly found in white matter areas in the
      central nervous system. In the adult brain, autotaxin is solely expressed in
      leptomeningeal cells and oligodendrocyte precursor cells. Following neurotrauma,
      autotaxin is strongly up-regulated in reactive astrocytes adjacent to the lesion.
      The present study revealed the cellular distribution of autotaxin in the
      developing and lesioned brain and implies a function of autotaxin in
      oligodendrocyte precursor cells and brain injuries.

PMID- 17192811
TI  - BH3-only proteins in tumorigenesis and malignant melanoma.
AB  - BH3-only proteins are a subset of the Bcl-2 family of apoptotic regulators. BH3
      only proteins function as 'damage sensors' in the cell; they are activated in
      response to cellular stress or DNA damage, whereupon they initiate apoptosis.
      Apoptosis is the primary mechanism by which the body rids itself of genetically
      defective cells and is critical for preventing the accumulation of cells with
      tumorigenic potential. Therefore, dysregulation of BH3-only proteins may promote
      tumorigenesis. Furthermore, functional apoptosis pathways are required for the
      success of most cancer treatments, including chemotherapy. Resistance to
      chemotherapy, as seen with malignant melanoma, often reflects an inability of
      tumor cells to undergo apoptosis. By deciphering the roles of BH3-only proteins
      in tumorigenesis, we may learn how to manipulate cell death pathways to overcome
      apoptotic resistance. This review summarizes the current knowledge of BH3-only
      proteins and how they contribute to tumorigenesis, with particular attention
      given to studies involving melanoma.

PMID- 17192812
TI  - Transcriptional regulation of Trk family neurotrophin receptors.
AB  - The Trk family of neurotrophin receptors plays essential roles in cell fate
      specification, survival, growth, and differentiation. Their expression patterns
      are complex and dynamically regulated under many physiological and pathological
      conditions. However, the molecular mechanisms that control their tissue-specific
      expression are largely unknown. In this report, we review current knowledge about
      the transcriptional regulation of Trk receptors.

PMID- 17192814
TI  - Design and implementation of gradient vector flow snake to detect a reference
      object in pelvic x-rays for preoperative total hip arthroplasty planning
      application.
AB  - The main interest of this research project is to promote automation in performing
      preoperative planning for hip joint replacement surgery using a special medical
      image viewing software, ViewPro. Preoperative planning is performed to carefully
      prepare the surgery and to accurately select the hip implants. The first step of
      preoperative planning is to calibrate the x-ray image to adjust the magnification
      factor. A femoral head implant is used as magnification factor reference.
      Automation is introduced by developing an algorithm to automatically detect this
      reference object in the image. The algorithm used for performing the automatic
      detection of the reference object is gradient vector flow (GVF) snake. A study
      has been performed to compare the newly developed semiautomatic algorithm to the
      old manual calibration algorithm. The results show a close relation between the
      two algorithms (less than 1% of average relative difference). It is concluded
      that the developed semiautomated algorithm can be used as an alternative for
      performing the manual calibration.

PMID- 17192813
TI  - Laparoscopic rectopexy.
AB  - Abdominal rectopexy has been advocated as the treatment of choice for complete
      rectal prolapse. Recurrence rates are low raging from 0-12% and fecal continence
      has been documented to improve in 3-75% of patients. As most patients are elderly
      and not always fit enough to undergo abdominal procedure, various perineal
      approaches have been advocated. Depending on the type and extent of the
      operation, these procedures have a recurrence of up to 38%. Laparoscopic
      rectopexy represents the latest development in the evolution of surgical
      treatment of rectal prolapse. This technique aims to combine the good functional
      outcome of the open abdominal procedure with the low postoperative morbidity of
      minimal invasive surgery. We present a laparoscopic rectopexy on 72-year-old lady
      with a 10-year history of fecal incontinence and mucosal rectal prolapse.
      Electronic supplementary material is available for this article at
      http://dx.doi.org/10.1007/s00464-006-0136-y.

PMID- 17192815
TI  - Comparison of techniques for correction of magnification of pelvic X-rays for hip
      surgery planning.
AB  - The aim of this study was to develop an accurate method for correction of
      magnification of pelvic x-rays to enhance accuracy of hip surgery planning. All
      investigated methods aim at estimating the anteroposterior location of the hip
      joint in supine position to correctly position a reference object for correction
      of magnification. An existing method-which is currently being used in clinical
      practice in our clinics-is based on estimating the position of the hip joint by
      palpation of the greater trochanter. It is only moderately accurate and difficult
      to execute reliably in clinical practice. To develop a new method, 99 patients
      who already had a hip implant in situ were included; this enabled determining the
      true location of the hip joint deducted from the magnification of the prosthesis.
      Physical examination was used to obtain predictor variables possibly associated
      with the height of the hip joint. This included a simple dynamic hip joint
      examination to estimate the position of the center of rotation. Prediction
      equations were then constructed using regression analysis. The performance of
      these prediction equations was compared with the performance of the existing
      protocol. The mean absolute error in predicting the height of the hip joint
      center using the old method was 20 mm (range -79 mm to +46 mm). This was 11 mm
      for the new method (-32 mm to +39 mm). The prediction equation is: height (mm) =
      34 + 1/2 abdominal circumference (cm). The newly developed prediction equation is
      a superior method for predicting the height of the hip joint center for
      correction of magnification of pelvic x-rays. We recommend its implementation in
      the departments of radiology and orthopedic surgery.

PMID- 17192816
TI  - From proficiency to expert, when does the learning curve for robotic-assisted
      prostatectomies plateau? The Columbia University experience.
AB  - To describe our single-institution experience with our first 70 consecutive
      robotic-assisted laparoscopic prostatectomies (RLPs) with particular focus on
      effect of learning curve on operative time, length of stay and blood loss. We
      also report our short-term outcome data in this heterogeneous cohort of men with
      prostate cancer (PCa). We reviewed our institutional database for the first 70
      consecutive RLPs performed by a single surgeon (DS) over a 21-month period (March
      2003 to December 2004). Surgical, pathologic and postoperative outcomes were
      analyzed. In order to evaluate the impact of the surgeon's and institution's
      learning curve on outcomes, the cases were divided into quartiles and stratified
      accordingly to identify trends. Ninety-nine percent (69/70) of all procedures
      were successfully completed robotically. Mean blood loss, operative time and mean
      length of stay were 231 ml, 264 min and 1.9 days, respectively. At follow-up, 76%
      of all patients were fully continent (no pads) and 93% (62/67) had undetectable
      PSA. The most dramatic improvement in surgical outcomes was seen within the first
      quartile of cases; however a statistically significant improvement trend existed
      throughout the series. This included a downward trend in operative time (P <
      0.00001), estimated blood loss (P < 0.00001), and length of hospital stay (P =
      0.003). This trend continued when controlled for in a multivariate analysis. Our
      results compare favorably with other RLP series as well as conventional
      laparoscopic series. Proficiency is achieved within the first 20 cases; however
      surgical outcomes continue to improve for RLP throughout the first 70 cases and
      perhaps beyond.

PMID- 17192817
TI  - Aspirin and tension-type headache.
AB  - Acetylsalicylic acid (ASA, Aspirin) is among the most used drugs worldwide. At
      present, Aspirin represents a quite versatile drug employed in the control of
      pain symptomatologies and in situations such as prevention of both ischaemic
      stroke and cardiovascular events. Aspirin causes inhibition of prostaglandin (PG)
      synthesis by inactivation of the cyclooxygenase (COX) enzyme. ASA constitutes the
      focus of new researches explaining more widely Aspirin's control of inflammation.
      The induction of the endogenous epimers lipoxins (Aspirin-triggered 15-epi
      lipoxins, ATLs) represents one of the most recent achievements. This particular
      feature of Aspirin is not shared by other NSAIDs. ASA is well known as a headache
      medication, figuring as a possible treatment choice in tension-type headache but
      also in acute migraine attacks. Furthermore, a new Aspirin formulation with a
      greater rapidity of action has been introduced. In conclusion, little information
      exists on the subject and more studies are required.

PMID- 17192818
TI  - Novel analysis of clonal diversification in blood B cell and bone marrow plasma
      cell clones in immunoglobulin light chain amyloidosis.
AB  - Immunoglobulin light chain amyloidosis (AL) is characterized by a limited clonal
      expansion of plasma cells and amyloid formation. Here, we report restriction in
      the diversity of VL gene usage with a dominance of clonally related B cells in
      the peripheral blood (PB) isotype-specific repertoire of AL patients. A rigorous
      quantification of lineage trees reveals presence of intraclonal variations in the
      PB clones compared to the bone marrow (BM) clones, which suggests a common
      precursor that is still subject to somatic mutation. When compared to normal BM
      and PB B cells, AL clones showed significant but incomplete impairment of
      antigenic selection, which could not be detected by conventional R and S mutation
      analysis. Therefore, graphical analysis of B cell lineage trees and mathematical
      quantification of tree properties provide novel insights into the process of B
      cell clonal evolution in AL.

PMID- 17192819
TI  - CTLA-4 gene exon-1 +49 A/G polymorphism: lack of association with autoimmune
      disease in patients with common variable immune deficiency.
AB  - The presence of the G allele of exon-1 +49 A/G polymorphisms of the cytotoxic T
      lymphocyte antigen 4 (CTLA-4) gene has been described as a risk factor associated
      with the development of autoimmune diseases. Since Common Variable Immune
      Deficiency (CVID) is associated with autoimmune manifestations in approximately
      25% of patients, we sought to examine the association of the CTLA-4 single
      nucleotide polymorphism with autoimmunity and other inflammatory complications.
      Sixteen of 47 CVID (34%) patients had a history of autoimmunity, and 15 (32%) had
      known granulomatous disease with or without lymphoid hyperplasia. CTLA-4 genotype
      frequencies were AA 40% (19), AG 45% (21), and GG 15% (7). Allele frequencies
      were A 63% and G 37%, similar to control populations. There were no significant
      associations between CTLA-4 exon-1 +49 A/G polymorphism and autoimmune or
      lymphoid hyperplasia and granulomatous disease in this mostly Caucasian CVID
      patient population.

PMID- 17192820
TI  - Solid substrate-room temperature phosphorescence method for the determination of
      trace Mn(II) based on oxidizing reaction of hydrogen peroxide using alpha,alpha'
      bipyridine as sensitizer.
AB  - A new solid substrate-room temperature phosphorescence (SS-RTP) method for the
      determination of trace manganese (II) has been established. It bases on the fact
      that fullerol (R) emits strong and stable room temperature phosphorescence (RTP)
      on filter paper substrate. H2O2 can oxidize R to cause the SS-RTP quenching. But
      manganese (II) can obstruct H2O2 to oxidize R, and enhance the RTP of R.
      alpha,alpha'-Bipyridine (Bipy) can sensitize the RTP. After adding Bipy, the
      DeltaI(p) enhances 7 times than that without Bipy. Under the optimum conditions,
      the linear dynamic range of this method is 0.016-1.12 pg spot(-1) with a
      detection limit (L.D.) of 4.6 fg spot(-1) (m(Mn(2+) is the absolute mass of
      Mn(2+)), and the regression equation of working curve is DeltaI(p)=25.20 + 63.55
      m(Mn(2+) (pg spot(-1)), n=6, r=0.9983. For 0.016 and 1.12 pg spot(-1) Mn(2+),
      RSDS are 4.3 and 4.8%, respectively (n=7). This method has been applied to the
      determination of trace manganese (II) in actual sample with high sensitivity and
      good selection. And the reaction mechanism of SS-RTP is discussed.

PMID- 17192821
TI  - Tracing lysozyme-lipid interactions with long-wavelength squaraine dyes.
AB  - The applicability of the two newly commercial available squaraine labels Square
      670-NHS and Seta-635-NHS to exploring protein-lipid interactions has been
      evaluated. The labels were conjugated to lysozyme (Lz) (squaraine-lysozyme
      conjugates below referred to as Square-670-Lz and Seta-635-Lz), a structurally
      well-characterized small globular protein displaying the ability to interact
      both, electrostatically and hydrophobically with lipids. The lipid component of
      the model systems was represented by lipid vesicles composed of zwitterionic
      lipids egg yolk phosphatidylcholine (PC) and 1-stearoyl-2-oleoyl-sn-glycero-3
      phosphocholine (SOPC), and their mixtures with anionic lipids either beef heart
      cardiolipin (CL) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG),
      respectively. Fluorescence intensity of Square-670-Lz was found to decrease upon
      association with lipid bilayer, while the fluorescence intensity of Seta-635-Lz
      displayed more complex behavior depending on lipid-to-protein molar ratio.
      Covalent coupling of squaraine labels to lysozyme exerts different influence on
      the properties of dye-protein conjugate. It was suggested that Square-670-NHS
      covalent attachment to Lz molecule enhances protein propensity for self
      association, while squaraine label Seta-635-NHS is sensitive to different modes
      of lysozyme-lipid interactions-within the L:P range 6-11, when hydrophobic
      protein-lipid interactions are predominant, an aggregation of membrane-bound
      protein molecules takes place, thereby decreasing the fluorescence intensity of
      Seta-635-Lz. At higher L:P values (from 22 to 148) when electrostatic
      interactions are enhanced fluorescence intensity of Seta-635-Lz increases with
      increasing lipid concentrations.

PMID- 17192822
TI  - Study on the new fluorescence enhancement system of Tb -N-(2 - pyridinyl)
      ketoacetamide-Et3N-Zn and its application.
AB  - A sensitive fluorescence enhancement system was developed for the determination
      of zinc (II). The fluorescence intensity of the Tb- N- (2 - Pyridinyl)
      ketoacetamide (PKA) system was greatly enhanced by the addition of triethylamine
      (Et(3)N) and zinc nitrate in the methanol solution. The excitation and emission
      wavelengths were 329 nm and 546 nm, respectively. Under optimal conditions, the
      fluorescence intensities varied linearly with the concentration of Zn(2+) in the
      range of 8.0 x 10(-7)-5.0 x 10(-6) M with a detection limit of 9.9 x 10(-8) M.
      The interferences of some substances were described. This method was applied to
      the determination of amounts of Zn(2+) in soybean, rice, and wheat, respectively.
      The results showed that the proposed procedure is a high selective, simple, and
      rapid method to the determination of Zn(2+) ion. The mechanism of fluorescence
      enhancement was also studied.

PMID- 17192823
TI  - The molecular diversity of different isolates of Beauveria bassiana (Bals.)
      Vuill. as assessed using intermicrosatellites (ISSRs).
AB  - Inter-microsatellite PCR (ISSR-PCR) markers were used to identify and to examine
      the genetic diversity of eleven Beauveria bassiana isolates with different
      geographic origins. The variability and the phylogenetic relationships between
      the eleven strains were analyzed using 172 ISSR-PCR markers. A high level of
      polymorphism (near 80%) was found using these molecular markers. Seven different
      isolates showed exclusive bands, and ISSR primer 873 was able to distinguish
      between all the strains. The dendrogram obtained with these markers is robust and
      in agreement with the geographical origins of the strains. All the isolates from
      the Caribbean region were grouped together in a cluster, while the other isolates
      grouped in the other cluster. The similarity exhibited between the two clusters
      was less than 50%. This value of homology shows the high genetic variability
      detected between the isolates from the Caribbean region and the other isolates.
      ISSR-PCR markers provide a quick, reliable and highly informative system for DNA
      fingerprinting, and allowed the identification of the different B. bassiana
      isolates studied.

PMID- 17192824
TI  - Chromosomal mapping of the major and minor ribosomal genes, (GATA)n and (TTAGGG)n
      by one-color and double-color FISH in the toadfish Halobatrachus didactylus
      (Teleostei: Batrachoididae).
AB  - The karyotype of Halobatrachus didactylus presents 46 chromosomes, composed of
      eight metacentric, 18 submetacentric, four subtelocentric, and 16 acrocentric
      chromosomes. The results of FISH showed that the major ribosomal genes were
      located in the terminal position of the short arm of a large submetacentric
      chromosome. They also showed a high variation in the hybridization signals. The
      products of amplification of 5S rDNA produced bands of about 420 pb. The PCR
      labeled products showed hybridization signals in the subcentromeric position of
      the long arm of a submetacentric chromosome of medium size. Double-color FISH
      indicated that the two ribosomal families are not co-located since they
      hybridized in different chromosomal pairs. Telomeres of all the chromosomes
      hybridized with the (TTAGGG)n probe. The GATA probe displayed a strong signal in
      the long arm of a submetacentric chromosome of medium size, in the subcentromeric
      position. The double-color FISH showed that the microsatellite GATA and the 5S
      rDNA gene are located in different chromosomal pairs. The majority presence of
      GATA probes in one pair of chromosomes is unusual and considering its
      distribution through different taxa it could be due to evolutionary mechanisms of
      heterochromatine accumulation, leading to the formation of differentiated sex
      chromosomes.

PMID- 17192825
TI  - HeLa cells treated with phytoglycoprotein (150 kDa) were killed by activation of
      caspase 3 via inhibitory activities of NF-kappaB and AP-1.
AB  - The Solanum nigrum Linne (SNL) has been traditionally used as a herbal agent in
      folk medicine for various cancers in Korea. We found that the SNL glycoprotein
      consists of carbohydrate (69.74%) and protein content (30.26%), which has mainly
      the hydrophobic amino acids containing glycine and proline. With respect to its
      characters, we evaluated the apoptotic effects of glycoprotein isolated from SNL
      in human cervical cancer cell. In the activity of the apoptotic related proteins
      [cytochrome c, caspase 8, 3 and poly (ADP-ribose) polymerase (PARP)], the results
      showed that SNL glycoprotein (50 microg/ml) has a stimulatory effect on
      cytochrome c release into cytosol, caspase 8, 3 activation and PARP cleavage in
      HeLa cells. To verify the possible mechanism for apoptotic activity of SNL
      glycoprotein in HeLa cells, the binding activities of transcription factors (NF
      kappaB and AP-1) and nitric oxide (NO) production was evaluated. The activities
      of NF-kappaB and AP-1 significantly decreased after SNL glycoprotein (50
      microg/ml) treatment for 4 h, compare to the control. Interestingly, there was no
      difference of the DNA binding activity between NF-kappaB and AP-1. Also, nitric
      oxide (NO) production was significantly declined at 50 microg/ml SNL glycoprotein
      for 4 h. Therefore, we speculated that SNL glycoprotein exhibits inhibitory
      effect on HeLa cells via apoptosis, and it may be a potential candidate in field
      of anticancer drug discovery.

PMID- 17192826
TI  - Endocrine modulation of a pheromone-responsive gene in the honey bee brain.
AB  - Pheromones cause dramatic changes in behavior and physiology, and are critical
      for honey bee colony organization. Queen mandibular pheromone (QMP) regulates
      multiple behaviors in worker bees (Slessor et al. in J Chem Ecol 31(11):2731
      2745, 2005). We also identified genes whose brain expression levels were altered
      by exposure to QMP (Grozinger et al. in Proc Natl Acad Sci USA 100(Suppl 2):14519
      14525, 2003). Kruppel-homolog 1 (Kr-h1) RNA levels were significantly
      downregulated by QMP, and were higher in foragers than in nurses (Whitfield et
      al. in Science 302(5643):296-299, 2003). Here we report on results of behavioral
      and pharmacological experiments that characterize factors regulating expression
      of Kr-h1. Foragers have higher brain levels of Kr-h1 than in-hive bees,
      regardless of age and pheromone exposure. Furthermore, forager Kr-h1 levels were
      not affected by QMP. Since the onset of foraging is caused, in part, by
      increasing juvenile hormone blood titers and brain octopamine levels, we
      investigated the effects of octopamine and methoprene (a juvenile hormone analog)
      on Kr-h1 expression. Methoprene produced a marginal (not significant) increase in
      Kr-h1 expression, but Kr-h1 brain levels in methoprene-treated bees were no
      longer downregulated by QMP. Octopamine did not modulate Kr-h1 expression. Our
      results demonstrate that the gene expression response to QMP is not hard-wired in
      the brain but is instead dependent on worker behavioral state.

PMID- 17192827
TI  - Historical reflections on the afterhyperpolarization--firing rate relation of
      vertebrate spinal neurons.
AB  - In mammalian spinal motoneurons (MNs), the slow component of the
      afterhyperpolarization (AHP) that follows the spike of each action potential is a
      major but not the sole determinant of the cells' firing rate. In this brief
      historical review, we emphasize four points about the AHP-firing rate relation.
      (1) There is a relatively sparse literature across vertebrates that directly
      addresses this topic. (2) After the advent of intracellular recording in the
      early 1950s, there was evidence from mammals to the contrary of an idea that
      subsequently became prevalent: that the high-firing rates attainable by spinal
      interneurons (INs) and low-threshold MNs was attributable to their small AHP at
      rheobase. (3) Further work is needed to determine whether our present findings on
      the AHP-firing rate relation of turtle cells generalize to the spinal neurons of
      other vertebrate species. (4) Relevant to point 3, substantial in vivo and in
      vitro work is potentially available in raw data used in reports on several
      mammalian and non-mammalian vertebrates. In summary, the factors in addition to
      the slow AHP that help determine spinal INs and MN firing rate deserve further
      evaluation across vertebrates, with relevant data already potentially available
      in several laboratories.

PMID- 17192828
TI  - [The design of the VISEP trial. Critical appraisal].
AB  - The survey transcript of the VISEP interventional trial "Prospective randomized
      multicenter study on the influence of colloid vs crystalloid volume resuscitation
      and of intensive vs conventional insulin therapy on outcome in patients with
      severe sepsis and septic shock" [Clinical trials.gov. identifier: NCT00135473;
      study start April 2003] comprises, according to the data of the year 2003,
      methodological shortcomings which challenge a priori the study design and thus
      the resolution of the purpose of the study, i.e., "determination of the influence
      of the studied volume and insulin interventions on morbidity and mortality of
      patients with severe sepsis and septic shock". The most important points of
      criticism are: 1. A volume therapy with exclusively crystalloids or colloids with
      the chosen colloid hyperoncotic, hyperchloremic HES solution (10% hydroxyethyl
      starch: 10% Hemohes) or the crystalloid solution with high lactate content
      (Sterofundin) is neither acceptable nor practicable, even if only due to
      exceeding the maximum dosage as recommended by the manufacturer. 2. The fact
      known since the year 2001 that high molecular weight, poorly biodegradable HES
      preparations can present an independent risk-factor for acute kidney failure in
      patients with sepsis or septic shock was ignored: the exclusion criterion of a
      serum-creatinine value of >320 micromol/l (>3.6 mg/dl) was doubled in relation to
      the manufacturer's specification. 3. The hyperoncotic colloid solution used (10%
      Hemohes) may only be employed for a brief period: it is highly hyperchloremic and
      causes extravascular hypohydration with consecutive reduction of renal excretion,
      which together with HES is a fatal combination. 4. The crystalloid solution used,
      i.e., Sterofundin, which contains 45 mmol/l lactate, is contraindicated with
      septic shock as it increases the patient's O2 consumption, hinders lactate
      diagnostics as a hypoxia marker by simultaneous lactate infusion, and through
      increased gluconeogenesis leads to hyperglycemia, at least with diabetics. 5. It
      is doubtful whether an intensified insulin therapy (Actrapid) can be successful
      if insulin is administered simultaneously with iatrogenic hyperglycemia as a
      result of lactate influx. Due to these flaws in the design of the VISEP trial,
      the only consequence can be that the results of the survey are unusable,
      especially with regard to the point "HES and kidney function". Thus, any further
      advance presentations and interpretations should be shelved in expectation of the
      authors' publication of all the data, in order to begin further discussions
      including the flaws in study design listed here.

PMID- 17192830
TI  - Biological, familial, and peer influences on dating in early adolescence.
AB  - The current study examined the joint contributions of pubertal maturation,
      parental monitoring, involvement in older peer groups, peer dating, and peer
      delinquency on dating in a sample of early adolescent boys and girls. The sample
      consisted of 784 adolescents (394 boys, 390 girls) enrolled in grades 5, 6, and 7
      who were followed for one year. In addition to measures of pubertal maturation
      and parental monitoring, adolescents and their peer group members completed
      indices of dating and delinquency. Average dating and delinquency scores for each
      participant's peer group network were computed. Results indicated that it was the
      combination of pubertal maturation, peer delinquency, and peer dating that
      explained increases in early dating. For boys only, parental monitoring was a
      significant predictor. The more knowledgeable parents were about their boys'
      activities, the lower the number of dating activities reported. These results
      highlight the importance of considering the joint effects of these biological and
      social predictors in understanding early dating. When rapid changes occur in all
      three domains, early dating is most likely to ensue. The findings of this study
      have practical importance. Parents and professionals who work closely with youth
      should attend to the special vulnerability of early maturing adolescents in the
      face of peer pressure and to the important role of parental monitoring in
      regulating dating activities.

PMID- 17192829
TI  - Inhibition of transforming growth factor-beta production in brain pericytes
      contributes to cyclosporin A-induced dysfunction of the blood-brain barrier.
AB  - : 1. The present study was designed to clarify whether brain pericytes and
      pericyte-derived transforming growth factor-beta1 (TGF-beta1) participate in
      cyclosporin A (CsA)-induced dysfunction of the blood-brain barrier (BBB).2. The
      presence of brain pericytes markedly aggravated CsA-increased permeability of
      MBEC4 cells to sodium fluorescein and accumulation of rhodamine 123 in MBEC4
      cells.3. Exposure to CsA significantly decreased the levels of TGF-beta1 mRNA in
      brain pericytes in pericyte co-cultures. Treatment with TGF-beta1 dose
      dependently inhibited CsA-induced hyperpermeability and P-glycoprotein
      dysfunction of MBEC4 cells in pericyte co-cultures.4. These findings suggest that
      an inhibition of brain pericyte-derived TGF-beta1 contributes to the occurrence
      of CsA-induced dysfunction of the BBB.

PMID- 17192831
TI  - The impact of sexual coercion on psychological, physical, and sexual well-being
      in a representative sample of Australian women.
AB  - It is well established that, compared to other women, women who have been forced
      or frightened into unwanted sexual activity have poorer psychological, physical,
      and sexual health. However, it is not clear whether particular experiences of
      sexual coercion, such as younger age when coerced or number of times coerced, are
      more likely to lead to poorer health status. This study of a representative
      sample of Australian women aged 16-59 years was designed to examine such
      associations. Of the 9134 women recruited for the study, 885 (21%) had been
      sexually coerced, which was defined as being forced or frightened into unwanted
      sexual activity. This study showed that any experience of sexual coercion was
      associated with poorer psychological, physical, and sexual health. The data
      revealed no consistent associations between health status and particular
      characteristics of sexual coercion, such as the age when women were coerced, the
      number of times they had been coerced, or the time since being coerced. Two of
      the few significant findings were that women who had been coerced more than once
      reported significantly greater psychosocial distress, and that women first
      coerced when aged 13-16 reported poorer physical well-being than women first
      coerced at younger or older ages. There was no significant association between
      whether women had consulted a psychologist or other professional counselor and
      better health status. The absence of consistent associations between health
      status and particular characteristics of sexual coercion indicates a need for
      care and support services for all women who have been sexually coerced.

PMID- 17192832
TI  - The compulsive sexual behavior inventory: psychometric properties.
AB  - Compulsive sexual behavior (CSB) is a putative clinical syndrome characterized by
      the experience of sexual urges, sexually arousing fantasies, and sexual behaviors
      that are recurrent, intense, and a distressful interference in one's daily life.
      Although the putative phenomenology of CSB has been described in the literature,
      the lack of a reliable, valid assessment tool has made investigation of
      prevalence, co-factors, and etiologic factors difficult. This study examined the
      further development of the Compulsive Sexual Behavior Inventory (CSBI) using a
      sample of 1,026 Latino men who have sex with men recruited and assessed using web
      based technology. The scale showed a two factor structure (control and violence).
      Further, the CSBI and its subscales showed indications of validity in that those
      engaging in CSB-type sexual behavior (being drunk or high, feeling lonely or
      depressed, and feeling driven) had scores indicative of greater CSB. Those with
      scores above the median had more sexual partners and engaged in more unprotected
      anal intercourse than those with CSBI scores below the median. Additionally, the
      instrument showed equivalence when administered in English and Spanish.

PMID- 17192833
TI  - Characteristics of sexual abuse in childhood and adolescence influence sexual
      risk behavior in adulthood.
AB  - Childhood and adolescent sexual abuse has been associated with subsequent (adult)
      sexual risk behavior, but the effects of force and type of sexual abuse on sexual
      behavior outcomes have been less well-studied. The present study investigated the
      associations between sexual abuse characteristics and later sexual risk behavior,
      and explored whether gender of the child/adolescent moderated these relations.
      Patients attending an STD clinic completed a computerized survey that assessed
      history of sexual abuse as well as lifetime and current sexual behavior.
      Participants were considered sexually abused if they reported a sexual experience
      (1) before age 13 with someone 5 or more years older, (2) between the ages of 13
      and 16 with someone 10 or more years older, or (3) before the age of 17 involving
      force or coercion. Participants who were sexually abused were further categorized
      based on two abuse characteristics, namely, use of penetration and force.
      Analyses included 1177 participants (n=534 women; n=643 men). Those who reported
      sexual abuse involving penetration and/or force reported more adult sexual risk
      behavior, including the number of lifetime partners and number of previous STD
      diagnoses, than those who were not sexually abused and those who were abused
      without force or penetration. There were no significant differences in sexual
      risk behavior between nonabused participants and those who reported sexual abuse
      without force and without penetration. Gender of the child/adolescent moderated
      the association between sexual abuse characteristics and adult sexual risk
      behavior; for men, sexual abuse with force and penetration was associated with
      the greatest number of episodes of sex trading, whereas for women, those who were
      abused with penetration, regardless of whether the abuse involved force, reported
      the most episodes of sex trading. These findings indicate that more severe sexual
      abuse is associated with riskier adult sexual behavior.

PMID- 17192835
TI  - Live birth following transfer of a cryopreserved embryo generated from a
      cryopreserved oocyte and a cryopreserved sperm: case report.
AB  - As is the case with non-frozen oocytes, the efficient and successful use of
      cryopreserved oocytes in human assisted reproduction is, in part, dependent on
      the ability to apply selection criteria when choosing the 'best' embryos for
      transfer from a cohort. In many cases this, in turn, will necessitate the
      cryopreservation of non-transferred embryos to minimise the risk of multiple
      pregnancy. It is therefore important to establish that an embryo, generated by
      fertilization of a frozen-thawed oocyte, can be capable of surviving subsequent
      cryopreservation while retaining the potential for normal development. In this
      case report, we document the delivery of a normal male infant following transfer
      of a frozen-thawed embryo, generated by the fertilization of a frozen-thawed
      oocyte by a frozen-thawed sperm.

PMID- 17192836
TI  - Route-dependent stereoselective pharmacokinetics of tramadol and its active O
      demethylated metabolite in rats.
AB  - The effects of route of administration on the stereoselective pharmacokinetics of
      tramadol (T) and its active metabolite (M1) were studied in rats. A single 20
      mg/kg dose of racemic T was administered through intravenous, intraperitoneal, or
      oral route to different groups of rats, and blood and urine samples were
      collected. Samples were analyzed using chiral chromatography, and pharmacokinetic
      parameters (mean +/- SD) were estimated by noncompartmental methods. Following
      intravenous injection, there was no stereoselectivity in the pharmacokinetics of
      T. Both enantiomers showed clearance values (62.5 +/- 27.2 and 64.4 +/- 39.0
      ml/min/kg for (+)- and (-)-T, respectively) that were equal or higher than the
      reported liver blood flow in rats. Similar to T, the area under the plasma
      concentration-time curves (AUCs) of M1 did not exhibit stereoselectivity after
      intravenous administration of the parent drug. However, the systemic availability
      of (+)-T was significantly (P < 0.05) higher than that of its antipode following
      intraperitoneal (0.527 +/- 0.240 vs. 0.373 +/- 0.189) and oral (0.307 +/- 0.136
      vs. 0.159 +/- 0.115) administrations. The AUC of the M1 enantiomers, on the other
      hand, remained mostly nonstereoselective regardless of the route of
      administration. Pharmacokinetic analysis indicated that the stereoselectivity in
      the pharmacokinetics of oral T is due to stereoselective first pass metabolism in
      the liver and, possibly, in the gastrointestinal tract. The direction and extent
      of stereoselectivity in the pharmacokinetics of T and M1 in rats were in
      agreement with those previously reported in humans, suggesting that the rat may
      be a suitable model for enantioselective studies of T pharmacokinetics.

PMID- 17192834
TI  - PEPT1 enhances the uptake of gabapentin via trans-stimulation of b0,+ exchange.
AB  - PURPOSE: The aims of this study were (1) to determine whether amino acid and
      dipeptide loading can improve the effective permeability of gabapentin and (2) to
      characterize the underlying mechanism that is responsible for this interaction.
      MATERIALS AND METHODS: An in situ single-pass rat intestinal perfusion model was
      used to assess the effective permeability of gabapentin in rat, in the absence
      and presence of cellular loading by amino acid and dipeptide mixtures. RESULTS:
      Compared to gabapentin alone, cellular loading with amino acid and dipeptide
      mixtures significantly improved the effective permeability of gabapentin by 46
      79% in jejunum and by 67-72% in ileum (p < or = 0.01). However, coperfusion of
      glycylsarcosine (i.e., PEPT1 substrate), methionine sulfoximine (i.e., glutamine
      synthase inhibitor), or lysine and arginine (i.e., b(0,+) substrates) with the
      amino acid and dipeptide mixtures compromised the intestinal uptake of
      gabapentin. CONCLUSIONS: These findings demonstrate, for the first time, a direct
      relationship between the PEPT1-mediated uptake of a dipeptide and the trans
      stimulated uptake of gabapentin (an amino acid-like drug) through the transport
      system b(0,+).

PMID- 17192837
TI  - Enantioseparation of extended metal atom chain complexes: unique compounds of
      extraordinarily high specific rotation.
AB  - Extended metal atom chains (EMACs) contain a linear metal chain wrapped by
      various ligands. Most complexes are of the form M(3)(dpa)(4)X(2), where M =
      metal, dpa = 2,2'-dipyridylamide, and X = various anions. The ligands form
      helical coils about the metal chain, which results in chiral EMAC complexes. The
      EMACs containing the metals Co and Cu were partially separated in polar organic
      mode using a vancomycin-based chiral stationary phase. Under similar conditions,
      two EMACs with Ni metal and varying anions could be baseline separated. The polar
      organic mode was used because of the instability of the compounds in aqueous
      mobile phases. Also, these conditions are more conducive to preparative
      separations. Polarimetric measurements on the resolved enantiomers of
      Ni(3)(dpa)(4)Cl(2) indicate that they have extraordinarily high specific
      rotations (on the order of 5000 deg cc/g dm).

PMID- 17192838
TI  - Solving multicomponent chiral separation challenges using a new SFC tandem column
      screening tool.
AB  - A tool for improved tandem column chiral supercritical fluid chromatography (SFC)
      method development screening was prepared by modification of a commercial
      analytical SFC instrument with two different software-controllable, six position
      high-pressure column selection valves, each controlling a bank of five different
      columns and a pass through line. The resulting instrument, which has the ability
      to screen 10 different individual columns and 25 different tandem column
      arrangements, is a useful tool for facilitating the screening of tandem column
      SFC arrangements for separation of complex mixtures of stereoisomers or other
      multicomponent mixtures. Strategies for optimal use of the instrument are
      discussed, and several examples of the use of the instrument in developing tandem
      SFC methods for resolution of multicomponent mixtures are presented.

PMID- 17192839
TI  - Synthesis and enantioselective rearrangement of (Z)-4-triphenylmethoxy-2,3
      epoxybutan-1-ol enantiomers.
AB  - Efficient enzyme catalyzed kinetic resolutions of a synthetically useful chiral
      building block, (Z)-4-triphenylmethoxy-2,3-epoxybutan-1-ol, are reported. The
      highest selectivities were achieved by Lipozyme TL IM and Amano Lipase PS enzymes
      in the presence of vinyl acetate. Enantiomeric enrichment of the optically active
      acetate isomer was accomplished by selective crystallization of the racemic part
      of the enantiomeric mixture. Enzyme catalyzed hydrolysis of the acetate also
      provided an optically pure epoxybutanol derivative. O-Benzylation of (+)-(Z)-1
      hydroxy-4-triphenylmethoxy-2,3-epoxybutane followed by super base promoted
      diastereo- and enantio-selective rearrangement resulted in (+)-(2R,3R,1'R)-3-[1
      hydroxy-2-(triphenylmethoxy)ethyl]-2-phenyloxetane in >98% ee and de.
      Configurations of the new optically active products were determined by chemical
      correlation.

PMID- 17192840
TI  - Asthma drug use and the development of Churg-Strauss syndrome (CSS).
AB  - PURPOSE: Case reports suggest that leukotriene modifier use may be associated
      with the onset of Churg-Strauss syndrome (CSS). Using pooled data from two nested
      case-control studies, we examined the association between asthma drug use and the
      development of CSS. METHODS: The study was performed in three US managed care
      organizations and a US national health plan with chart access and complete
      electronic pharmacy data, with a covered population of 13.9 million. There were
      47 cases of possible or definite CSS and 4700 asthma drug user controls
      identified between January 1, 1995 and December 31, 2002. We examined exposure to
      asthma drugs in cases and controls, including leukotriene modifiers (6 cases and
      202 controls), in the two to 6 months prior to the onset of adjudicated CSS.
      RESULTS: While the crude association between use of leukotriene modifiers and CSS
      was strong (odds ratio (OR) 4.00, 95% confidence interval (CI): 1.49-10.60), in a
      multivariable analysis controlling for use of oral corticosteroids, inhaled
      corticosteroids, and number of categories of asthma drugs dispensed, there was no
      significant association (OR 1.32, 95% CI: 0.44-3.96). Use of inhaled and oral
      corticosteroids, evaluated as markers of asthma severity, were associated with
      CSS (OR 3.07, 95% CI: 1.34-7.03 and OR 5.36, 95% CI: 2.51-11.45, respectively).
      CONCLUSIONS: No association was found between CSS and leukotriene modifiers after
      controlling for asthma drug use However, it is not possible to rule out modest
      associations with asthma treatments given CSS is so rare and so highly correlated
      with asthma severity, suggesting further investigation is warranted.

PMID- 17192841
TI  - Cancer risks in thiazolidinedione users compared to other anti-diabetic agents.
AB  - PURPOSE: We conducted three nested case-control studies to evaluate the risk of
      breast, colon, and prostate cancers developing in patients exposed to
      thiazolidinediones (TZDs) compared with other anti-diabetic agents. METHODS:
      Cancer cases were matched to five controls by age, gender, calendar year, and
      time in the database from a cohort of 1 26 971 diabetic patients taking anti
      diabetic medication in the US Integrated Healthcare Information Services
      database. Five hundred thirteen breast cancer cases were matched with 2557
      controls, 408 cases of colon cancer were matched with 2027 controls and 643 cases
      of prostate cancer were matched with 3176 controls. Exposure to an anti-diabetic
      agent within 90 days preceding the index date was defined as recent exposure and
      at any time during the follow-up was defined as ever exposed. RESULTS: The
      adjusted odds ratios and 95%CI of cancer from ever exposure to TZDs compared to
      oral monotherapy, oral dual therapy, oral triple therapy, insulin monotherapy,
      insulin and oral therapy and all non-TZD anti-diabetic agents were, respectively
      for breast cancer: 0.91 (0.69-1.20), 0.80 (0.56-1.14), 0.87 (0.32-2.35), 1.27
      (0.61-2.67), 0.71 (0.36-1.37), 0.89 (0.68-1.15); for colon cancer: 1.06 (0.80
      1.40), 1.12 (0.77-1.63), 1.73 (0.39-7.78), 4.46 (1.05-19.00), 1.06 (0.50-2.26)
      1.03 (0.80-1.32) and for prostate cancer: 1.08 (0.85-1.37), 0.89 (0.66-1.21);
      0.82 (0.33-2.06); 1.80 (0.79-4.07), 1.10 (0.55-2.18), 1.04 (0.83-1.31). Results
      for exposure within 90 days of the date of the cancer were similar. CONCLUSIONS:
      Our findings suggest that the effect of TZDs on the likelihood of development of
      the cancers studied (colon, prostate and breast) appears to be neutral and do not
      support a beneficial or deleterious effect of TZD on the cancers studied.

PMID- 17192842
TI  - Hepatitis B vaccine and risk of autoimmune thyroid disease: a Vaccine Safety
      Datalink study.
AB  - PURPOSE: Hepatitis B vaccine has been postulated as a possible cause of
      autoimmune disorders, including autoimmune thyroid diseases (ATD). Cases of
      Graves' disease and Hashimoto's thyroiditis, following hepatitis B vaccine have
      been reported to the Vaccine Adverse Events Reporting System (VAERS). To test the
      hypothesis that hepatitis B vaccine increases the risk of ATD, we conducted a
      case-control study, within the Vaccine Safety Datalink project. METHODS: We
      identified potential cases of Graves' disease and Hashimoto's thyroiditis, among
      persons aged 18-69 years from administrative data recorded by three health
      maintenance organizations (HMOs) and verified cases by medical record review.
      Controls were frequency-matched to cases by birth year, sex, and study site.
      Vaccine information was collected from administrative records, chart review, and
      telephone interviews with study subjects. We enrolled 355 Graves' disease cases,
      418 Hashimoto's thyroiditis cases, and 1102 controls. We assessed the association
      between ever-receipt of hepatitis B vaccine, as well as receipt of hepatitis B
      vaccine less than 1 year, 1-5 years and at least 5 years prior to the index date,
      and the risk of ATD. RESULTS: Ever-receipt of hepatitis B vaccine was not
      associated with risk of Graves' disease (odds ratio (OR), 0.90; 95% confidence
      interval (CI), 0.62-1.32) or Hashimoto's thyroiditis (OR, 1.23; 95%CI, 0.87
      1.73). There was also no association between the time interval since receipt of
      hepatitis B vaccination and either outcome. CONCLUSIONS: We did not observe an
      increased risk of Graves' disease or Hashimoto's thyroiditis, following receipt
      of hepatitis B vaccine.

PMID- 17192843
TI  - Specific membrane recruitment of Uso1 protein, the essential endoplasmic
      reticulum-to-Golgi tethering factor in yeast vesicular transport.
AB  - Uso1 is a yeast essential protein that functions to tether vesicles in the ER-to
      Golgi transport. Its recruitment to the ER-derived vesicles has been demonstrated
      in in vitro membrane transport systems using semi-intact cells. Here we report
      that the binding of Uso1 to specific membranes can be detected through simple
      sucrose density block centrifugation. The purified Uso1 protein binds to slowly
      sedimenting membranes generated from rapidly sedimenting P10 membranes. These
      membranes were produced dependent on ATP hydrolysis, contained COPII vesicle
      components, but had neither of the coat subunits or ER proteins, which indicates
      that they were representative of the uncoated ER-derived COPII vesicles. The
      slowly sedimenting membranes of different origins were physically linked when
      they were mixed in the presence of Uso1. The C-terminal acidic region was not
      required in membrane binding. The presence of membranes to which Uso1 could bind
      in the yeast cell lysate was detected using the current method.

PMID- 17192845
TI  - Factors involved in anaerobic growth of Saccharomyces cerevisiae.
AB  - Life in the absence of molecular oxygen requires several adaptations.
      Traditionally, the switch from respiratory metabolism to fermentation has
      attracted much attention in Saccharomyces cerevisiae, as this is the basis for
      the use of this yeast in the production of alcohol and in baking. It has also
      been clear that under anaerobic conditions the yeast is not able to synthesize
      sterols and unsaturated fatty acids and that for anaerobic growth these have to
      be added to the media. More recently it has been found that many more factors
      play a role. Several other biosynthetic reactions also require molecular oxygen
      and the yeast must have alternatives for these. In addition, the composition of
      the cell wall and cell membrane show major differences when aerobic and anaerobic
      cells are compared. All these changes are reflected by the observation that the
      transcription of more than 500 genes changes significantly between aerobically
      and anaerobically growing cultures. In this review we will give an overview of
      the factors that play a role in the survival in the absence of molecular oxygen.

PMID- 17192844
TI  - The end1 gene of Schizosaccharomyces pombe coding for a DNase is identical with
      the pnu1 gene coding for an RNase.
AB  - The DNA nuclease activity encoded by the end1 gene, and its inactivation by
      mutation, was described in connection with the characterization of DNA
      topoisomerases in the fission yeast Schizosaccharomyces pombe (Uemura and
      Yanagida, 1984). Subsequently, end1 mutant strains were used for the preparation
      of cell extracts for the study of enzymes and intermediates involved in DNA
      metabolism. The molecular identification of the end1 gene and its identity with
      the pnu1 gene is presented. The end1-458 mutation alters glycine to glutamate in
      the conserved motif TGPYLP. The pnu1 gene codes for an RNase that is induced by
      nitrogen starvation (Nakashima et al., 2002b). Thus, the End1/Pnu1 protein, like
      related mitochondrial proteins in other organisms, is an example of a sugar-non
      specific nuclease. The analysis of strains carrying a pnu1 deletion revealed no
      defects in meiotic recombination and spore viability.

PMID- 17192846
TI  - R115777 (Zarnestra)/Zoledronic acid (Zometa) cooperation on inhibition of
      prostate cancer proliferation is paralleled by Erk/Akt inactivation and reduced
      Bcl-2 and bad phosphorylation.
AB  - Zoledronic acid (ZOL) has proved activity in bone metastases from prostate cancer
      through inhibition of mevalonate pathway and of prenylation of intracellular
      proteins. We have reported that ZOL synergizes with R115777 farnesyltransferase
      inhibitor (FTI, Zarnestra) in inducing apoptosis and growth inhibition on
      epidermoid cancer cells. Here, we have studied the effects of the combination of
      these agents in prostate adenocarcinoma models and, specifically, on androgen
      independent (PC3 and DU145) and -dependent (LNCaP) prostate cancer cell lines. We
      have found that ZOL and R115777 were synergistic in inducing both growth
      inhibition and apoptosis in prostate adenocarcinoma cells. These effects were
      paralleled by disruption of Ras-->Erk and Akt survival pathways, consequent
      decreased phosphorylation of both mitochondrial bcl-2 and bad proteins, and
      caspase activation. Finally, ZOL/R115777 combination induced cooperative effects
      also in vivo on tumor growth inhibition of prostate cancer xenografts in nude
      mice with a significant survival increase. These effects were paralleled by
      enhanced apoptosis and inactivation of both Erk and Akt. In conclusions, the
      combination between ZOL and FTI leads to enhanced anti-tumor activity in human
      prostate adenocarcinoma cells likely through a more efficacious inhibition of ras
      dependent survival pathways and consequent bcl-related proteins-dependent
      apoptosis.

PMID- 17192847
TI  - Antiangiogenic activity of the endocannabinoid anandamide: correlation to its
      tumor-suppressor efficacy.
AB  - Endocannabinoids are now emerging as suppressors of key cell-signaling pathways
      involved in cancer cell growth, invasion, and metastasis. We have previously
      observed that the metabolically stable anandamide analog, 2-methyl-2'-F
      anandamide (Met-F-AEA) can inhibit the growth of thyroid cancer in vivo. Our
      hypothesis was that the anti-tumor effect observed could be at least in part
      ascribed to inhibition of neo-angiogenesis. Therefore, the aim of this study was
      to assess the anti-angiogenic activity of Met-F-AEA, to investigate the molecular
      mechanisms underlying this effect and whether Met-F-AEA could antagonize tumor
      induced endothelial cell sprouting. We show that Met-F-AEA inhibited bFGF
      stimulated endothelial cell proliferation, in a dose-dependent manner, and also
      induced apoptosis, both effects reliant on cannabinoid CB1 receptor stimulation.
      Analyzing the signaling pathways implicated in angiogenesis, we observed that the
      bFGF-induced ERK phosphorylation was antagonized by Met-F-AEA, and we found that
      p38 MAPK was involved in Met-F-AEA-induced apoptosis. Moreover, Met-F-AEA was
      able to inhibit bi-dimensional capillary-like tube formation and activity of
      matrix metalloprotease MMP-2, a major matrix degrading enzyme. Importantly, we
      demonstrated that Met-F-AEA is also functional in vivo since it inhibited
      angiogenesis in the chick chorioallantoic neovascularization model. Finally, Met
      F-AEA inhibited tumor-induced angiogenesis in a three-dimensional model of
      endothelial and thyroid tumor cell (KiMol) spheroids co-cultures in different 3-D
      polymeric matrices that resemble tumor microenvironment and architecture. Thus,
      our results suggest that anandamide could be involved in the control of cancer
      growth targeting both tumor cell proliferation and the angiogenic stimulation of
      the vasculature.

PMID- 17192848
TI  - Involvement of NO/cGMP signaling in the apoptotic and anti-angiogenic effects of
      beta-lapachone on endothelial cells in vitro.
AB  - Neovascularization is an essential process in tumor development, it is
      conceivable that anti-angiogenic treatment may block tumor growth. In
      angiogenesis, nitric oxide (NO) is an important factor which mediates vascular
      endothelial cell growth and migration. beta-Lapachone (3,4-dihydro-2,2-dimethyl
      2H-naphtho-[1,2-b]pyran-5,6-dione), a natural product extracted from the lapacho
      tree (Tabebuia avellanedae), has been demonstrated to possess anti-cancer and
      anti-viral effects. Whether beta-lapachone can induce endothelial cell death or
      has an anti-angiogenic effect is still an enigma. We investigated the in vitro
      effect of beta-lapachone on endothelial cells, including human vascular
      endothelial cell line, EAhy926, and human umbilical vascular endothelial cells
      (HUVEC). Our results revealed that (1) the intracellular cGMP levels and the
      mitochondria membrane potential (MMP) decreased, and calpain and caspases were
      activated, during beta-lapachone-induced endothelial cell death; (2) co-treatment
      with calpain inhibitors (ALLM or ALLN) or the intracellular calcium chelator,
      BAPTA, but not the general caspase inhibitor, zVAD-fmk, provided significant
      protection against apoptosis by preventing the beta-lapachone-induced MMP
      decrease and cytoplasmic calcium increase; (3) addition of NO downregulated the
      beta-lapachone-induced cGMP depletion and protected the cells from apoptosis by
      blocking the MMP decrease and the calcium increase; and (4) exogenous NO protects
      endothelial cells against the cell death induced by beta-lapachone, but not the
      anti-angiogenic effect. From all the data above, we demonstrated that NO can
      attenuate the apoptotic effect of beta-lapachone on human endothelial cells and
      suggest that beta-lapachone may have potential as an anti-angiogenic drug.

PMID- 17192849
TI  - Role of human LZIP in differential activation of the NF-kappaB pathway that is
      induced by CCR1-dependent chemokines.
AB  - Human leucine zipper protein (LZIP) associates with CC chemokine receptor 1
      (CCR1) and this protein-protein interaction should play an important role in
      leukocyte cell mobility. LZIP is known to regulate leukotactin-1 (Lkn-1)
      dependent cell migration without affecting the chemotactic activities of other CC
      chemokines that bind to CCR1. Since Lkn-1 is engaged in the transcriptional
      activation of nuclear factor kappaB (NF-kappaB) and subsequent activation of the
      chemoattractant ability of leukocytes, we investigated the regulatory role of
      LZIP in the NF-kappaB pathway that is induced by CCR1-dependent chemokines. LZIP
      increased NF-kappaB-dependent luciferase activity in response to Lkn-1 in
      HOS/CCR1 cells and THP-1 cells. However, the NF-kappaB-dependent luciferase
      activities induced by other CCR1-dependent chemokines were not affected by LZIP
      overexpression. LZIP also increased Lkn-1-induced chemotactic activity through
      activation of the NF-kappaB pathway, whereas LZIP did not affect either the
      transactivation of NF-kappaB or the chemotactic activities induced by other CCR1
      dependent chemokines. Western blot analysis showed that LZIP increased the
      degradation of IkappaBalpha induced by Lkn-1 but not by other CCR1-dependent
      chemokines. Results from electrophoretic mobility shift assay (EMSA) showed that
      LZIP enhanced the Lkn-1-induced DNA-binding activity of NF-kappaB. These data
      indicate that LZIP functions as a positive regulator in the NF-kappaB activation
      pathway that is triggered by Lkn-1 without affecting the transcriptional
      activation of NF-kappaB induced by other CCR1-dependent chemokines.

PMID- 17192850
TI  - Revised procedures for yeast metabolites extraction: application to a glucose
      pulse to carbon-limited yeast cultures, which reveals a transient activation of
      the purine salvage pathway.
AB  - In this study we have revised our original procedure of yeast metabolites
      extraction. We showed that: (a) less than 5% of intracellular metabolites leaks
      out during the step of rapid arrest of cellular metabolism by quenching yeast
      cells into a 60% methanol solution kept at -40 degrees C; and (b) with a few
      exception, the stability of metabolites were not altered during the 3 min boiling
      procedure in a buffered ethanol solution. However, there was a loss of external
      added metabolites of 5-30%, depending on the type of metabolites. This was mainly
      attributable to their retention on cellular debris after ethanol treatment, which
      prevented centrifugation of the cellular extracts before evaporation of ethanol.
      We further simplified our previous high-performance ionic chromatography (HPIC)
      techniques for easier, more reliable and robust quantitative measurements of
      organic acids, sugar phosphates and sugar nucleotides, and extended these
      techniques to purine and pyrimidine bases, using a variable wavelength detector
      set at 220 and 260 nm in tandem with a pulsed electrochemical or suppressed
      conductivity detector. These protocols were successfully applied to a glucose
      pulse to carbon-limited yeast cultures on purines metabolism. This study showed
      that glucose induced a fast activation of the purine salvage pathway, as
      indicated by a transient drop of ATP and ADP with a concomitant rise of IMP and
      inosine. This metabolic perturbation was accompanied by a rapid increase in the
      activity of the ISN1-encoded specific IMP-5'-nucleotidase. The mechanism of this
      activation remains to be determined.

PMID- 17192851
TI  - A flexible protein linker improves the function of epitope-tagged proteins in
      Saccharomyces cerevisiae.
AB  - Epitope tagging permits the detection of proteins when protein-specific
      antibodies are not available. However, the epitope tag can reduce the function of
      the tagged protein. Here we describe a cassette that can be used to introduce an
      eight amino acid flexible linker between multiple Myc epitopes and the open
      reading frame of a given gene. We show that inserting the linker improves the in
      vivo ability of the telomerase subunits Est2p and Est1p to maintain telomere
      length. The methods used here are generally applicable to improve the function of
      tagged proteins in both Saccharomyces cerevisiae and Schizosaccharomyces pombe.

PMID- 17192852
TI  - Attachment of MAL32-encoded maltase on the outside of yeast cells improves
      maltotriose utilization.
AB  - The fermentation of maltotriose, the second most abundant fermentable sugar in
      wort, is often incomplete during high-gravity brewing. Poor maltotriose
      consumption is due to environmental stress conditions during high-gravity
      fermentation and especially to a low uptake of this sugar by some industrial
      strains. In this study we investigated whether the use of strains with an alpha
      glucosidase attached to the outside of the cell might be a possible way to reduce
      residual maltotriose. To this end, the N-terminal leader sequence of Kre1 and the
      carboxy-terminal anchoring domain of either Cwp2 or Flo1 were used to target
      maltase encoded by MAL32 to the cell surface. We showed that Mal32 displayed on
      the cell surface of Saccharomyces cerevisiae laboratory strains was capable of
      hydrolysis of alpha-1,4-linkages, and that it increased the ability of a strain
      lacking a functional maltose permease to grow on maltotriose. Moreover, the
      enzyme was also expressed and found to be active in an industrial strain. These
      data show that expressing a suitable maltase on the cell surface might provide a
      means of modifying yeast for more complete maltotriose utilization in brewing and
      other fermentation applications.

PMID- 17192853
TI  - The KlSTE2 and KlSTE3 genes encode MATalpha- and MATa-specific G-protein-coupled
      receptors, respectively, which are required for mating of Kluyveromyces lactis
      haploid cells.
AB  - Mating in yeast is initiated by binding of pheromone to G-protein-coupled
      receptors expressed in haploid cells. We analysed the role of KlSte2p and KlSte3p
      receptors in the Kluyveromyces lactis mating pathway. By sequence analysis,
      KlSte2p and KlSte3p are the homologues of the Saccharomyces cerevisiae alpha
      pheromone and a-pheromone receptors, respectively. However, by expression
      experiments, we determined that KlSTE2 gene is expressed in the cells typified as
      MATalpha and therefore is the receptor for the K. lactis a-pheromone and KlSTE3
      gene is expressed in the MATa cells and binds the alpha-pheromone. The KlSTE2
      gene is silent in MATa cells, while it is highly expressed in MATalpha cells, and
      conversely the KlSTE3 gene is expressed in MATa cells and repressed in MATalpha
      cells. Disruption mutants of both genes were found to be sterile, and this defect
      is reversed by plasmidic copies of each gene. The cytoplasmic C-terminus of
      KlSte3p interacts strongly with the KlGpa1p (Galpha) subunit, which is involved
      in the transduction of the pheromone stimulus to induce mating. Remarkably, this
      same domain does not interact with a constitutive active allele of the Galpha
      subunit, indicating that the C-terminus is able to discriminate between the
      active (GTP-bound) and inactive (GDP-bound) forms of the Galpha subunit.

PMID- 17192854
TI  - Risk factors for new-onset diabetes mellitus following liver transplantation and
      impact of hepatitis C infection : an observational multicenter study.
AB  - New-onset diabetes mellitus (NODM) remains a common complication of liver
      transplantation (LT). We studied incidence and risk factors in 211 French
      patients who had undergone a primary LT between 6 and 24 months previously. This
      is a cross-sectional and retrospective multicenter study. Data were collected on
      consecutive patients at a single routine post-LT consultation. Demographic
      details, immunosuppressive regimens, familial and personal histories, hepatitis
      status, and cardiovascular risk were analyzed to compare those who developed NODM
      (American Diabetes Association/World Health Organization criteria) with the
      others. The overall incidence of NODM was 22.7%: 24% in tacrolimus (Tac)-treated
      patients (n = 175; 82.9%) and 16.7% in cyclosporine-treated patients (n = 36;
      17.1%). A total of 81% of the cases were diagnosed within 3 months of LT (M3).
      Among hepatitis C virus (HCV)-infected (HCV(+)) patients, NODM incidence was
      41.7% whereas among those patients negative for this virus (HCV(-)), the
      incidence was only 18.9% (P = 0.008). In Tac-treated patients, the incidence of
      NODM in the HCV(+) patients was significantly higher than in the HCV(-) patients
      (46.7% and 19.3%, respectively, P = 0.0014). Only 1 of 6 (16.7%) of the HCV(+)
      patients developed NODM on cyclosporine. Other independent pretransplantation
      risk factors for NODM included impaired fasting glucose (IFG) and a maximum
      lifetime body-mass index (BMI) over 25 kg/m2. In conclusion, emergence of NODM
      after LT is related to risk factors that can be detected prior to the graft, like
      maximum lifetime BMI, IFG, and HCV status. Tac induced a significantly higher
      incidence of NODM in the HCV(+) compared to the HCV(-) patients. The treatment
      should therefore be tailored to the patient's risk especially in case of HCV
      infection.

PMID- 17192855
TI  - The first two cases of living donor liver transplantation using dual grafts in
      Europe.
AB  - The major limitation in adult-to-adult living donor liver transplantation (LDLT)
      is an adequate graft size with special regard to the safety of the donor. Only
      20% of the evaluated donors are suitable to donate the right liver, depending
      mainly on the critical remnant liver volume. We report 2 cases of adult-to-adult
      LDLT using dual grafts. In the first case we implanted a left lateral lobe
      together with a left lobe; in the second case we used a left lateral and a right
      lobe. Dual graft LDLT solves the problem of graft-size insufficiency and avoids
      critical right lobectomy in the donor. This procedure can be safely performed and
      opens up the possibility of LDLT to even more families in the Western world.

PMID- 17192856
TI  - Acute myocardial infarction after live donor liver surgery.
AB  - Acute myocardial infarction is a tedious risk inherent in all major surgeries.
      Preoperative assessment has been directed mainly to assess its risk because it
      carries with it a very high mortality. Living donor liver transplantation has
      been subject to inquest not only because of the morbidity risk but also because
      of the mortality risk it carries to the live donor. We report a case of a 39-year
      old donor who died of acute myocardial infarction following right-lobe donor
      hepatectomy. In conclusion, to our knowledge this is the first reported case of
      mortality due to a cardiac event following donor surgery.

PMID- 17192858
TI  - Response to letter from P. Salander 2006;15:647-649.

PMID- 17192857
TI  - Acute graft-versus-host disease after liver transplantation: role of withdrawal
      of immunosuppression in therapeutic management.
AB  - Graft-versus-host disease (GVHD) after liver transplantation is rare but
      associated with a very high mortality (over 85%). Most treatments focus on
      increasing immunosuppression, addition of antibody preparations such as OKT3 and
      antithymocyte globulin to eliminate the donor lymphocytes, and supporting
      myelopoiesis by use of cytokines. However, the results are very poor. We reasoned
      that a better therapeutic approach would be to reduce the immunosuppression and
      allow the patient's immune system an opportunity to reject the allograft donor T
      cells. We tested this novel therapeutic approach in 3 patients diagnosed with
      GVHD. Two patients had rapid loss of donor T cell chimerism and resolution of
      their symptoms. The other patient continued to progress to severe GVHD and died.
      The patients who responded to withdrawal of immunosuppression had a later onset
      of symptoms and a lower level of donor CD3+ T cells at the start of treatment. We
      conclude that larger studies are needed to further evaluate these results and to
      determine what factors may affect the likelihood that a patient may respond to
      this approach.

PMID- 17192859
TI  - Terbinafine-induced hepatic failure requiring liver transplantation.
AB  - Drug-induced liver disease accounts for about 50% of acute or subacute liver
      failure in the United States. United Network of Organ Sharing (UNOS) data suggest
      8%-20% of liver transplantation in this country per year is for fulminant liver
      failure due to drugs. Even though the most common medication implicated in acute
      liver injury is acetaminophen (75%), there are numerous other drugs that are
      responsible for acute and chronic liver injury. A variety of antifungal
      medications are known to cause a wide range of liver injury from a mild
      hepatocellular-cholestatic injury pattern to acute/subacute liver failure.
      Terbinafine is one of the antifungals that have been associated with such liver
      injuries. We report a case of terbinafine-induced severe liver failure requiring
      liver transplantation.

PMID- 17192860
TI  - Left ventricular dysfunction: a hidden risk in patients undergoing liver
      transplantation.

PMID- 17192861
TI  - Oropharyngeal plasmacytic hyperplasia in a post-liver transplant recipient:
      morphologic and histologic signs.

PMID- 17192862
TI  - Choledochotomy in live liver donors.

PMID- 17192864
TI  - Quality of life in patients with hepatocellular carcinoma received surgical
      resection.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one the most common malignancies in
      the world. As the prognosis for HCC patients is poor, the quality of life (QOL)
      is becoming more important on the outcome assessments. The aim of this study was
      to evaluate QOL in HCC patients. METHODS: A total of 161 patients with HCC were
      enrolled at a university hospital. Most of these patients received surgical
      resections. They were assessed with Taiwan versions of WHOQOL-BREF, EORTC QLQ
      C30, and utility measures. The WHOQOL-BREF domain scores for the HCC patients
      were compared to healthy normative Taiwan population, using general linear models
      controlling for gender and age. Multiple logistic regressions were applied to
      explore association between a better QOL and clinical/sociodemographic variables.
      RESULTS: Compared with healthy people, the HCC patients had reduced QOL in
      physical domains, but better environmental QOL. After controlling gender, age,
      education, and employment, duration of HCC more than 1 year was associated with
      better QOL scores. WHOQOL-BREF could be cross-validated with EORTC QLQ-C30.
      CONCLUSIONS: Survival over 1 year was associated with better QOL in HCC patients.
      WHOQOL-BREF could be a valid QOL instrument for the assessments of QOL in HCC
      patients.

PMID- 17192865
TI  - Outcome of surgical treatment for recurrent thymic epithelial tumors with
      reference to world health organization histologic classification system.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to clarify the significance
      of surgical treatment for recurrent thymic epithelial tumors with reference to
      the World Health Organization (WHO) histological classification system. PATIENTS:
      Among 67 patients with tumor recurrence, 22 underwent a re-resection. There were
      1 patient with a type AB tumor, 5 with type B1 tumors, 10 with type B2 tumors, 5
      with type B3 tumors, and 1 with a carcinoma. RESULTS: The 10-year survival rate
      following the initial resection was 70% in patients who underwent a re-resection
      and 35% in those who did not. The average intervals from the initial resection to
      re-resection were 10.3, 7.8, 6.0, 2.4, and 2.6 years for patients with type AB,
      B1, B2, B3 tumors, and carcinoma, respectively. The patient with a type AB tumor
      was alive at 2.4 years after re-resection, 12.7 years after the initial
      resection. The 5-year survival rates following re-resection in the patients with
      type B1, B2, and B3 tumors were 100, 56, and 60, respectively. The patient with a
      carcinoma died as a result of the tumor 2 years after re-resection. CONCLUSION:
      WHO histological classification indicates the outcome of surgical treatment for
      recurrent thymic epithelial tumors.

PMID- 17192866
TI  - Feasibility of concurrent adjuvant chemotherapy and radiotherapy after breast
      conserving surgery in early breast cancer.
AB  - BACKGROUND: The optimal sequence of chemotherapy (CT) and radiotherapy (RT)
      remains uncertain after breast-conserving surgery (BCS). The current study was
      performed to evaluate whether the concurrent RT with CT increases the toxicities.
      METHODS: Two hundred and thirty-eight patients with stages I and II breast
      cancers were prospectively allocated to concurrent CT and RT (n = 133) and
      sequential CT and RT (n = 105) after BCS. In the sequential group, RT was started
      after the completion of three cycles of CT and additional three cycles of CT were
      delivered after RT. RESULTS: There was no significant difference in Grade 3 or 4
      hematologic toxicities during CT between the two groups. Radiation related
      adverse effects were not different between the two groups. During the median
      follow-up period of 42 months (range: 16-60 months), 18 patients (13.5%) of the
      concurrent group had systemic recurrence of breast cancer, whereas 20 patients
      (19.1%) of the sequential group had systemic recurrence. Disease-free survival
      and local recurrence were not different between the two groups. CONCLUSIONS:
      Concurrent CT and RT were not associated with increased toxicity and showed
      reasonable cosmetic results. The current study indicates that concurrent RT and
      CT after BCS is a feasible treatment modality with an advantage of shortening the
      treatment time.

PMID- 17192867
TI  - Hedgehog signaling pathway is a possible therapeutic target for gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: It has been shown that the hedgehog (Hh) signaling
      pathway is activated in gastric cancer. To investigate the viability of the Hh
      pathway as a therapeutic target, we analyzed activation of the Hh pathway in
      gastric cancer. METHODS: Surgically resected gastric carcinoma specimens and
      lymph nodes were analyzed immunohistochemically. We used the percentage of cancer
      cells with nuclear translocation of Gli1 as a marker of Hh pathway activation.
      RESULTS: Nuclear localization of Gli1 was higher in 28 undifferentiated-type
      tumors than in 30 differentiated-type tumors. Eighteen of the fifty-eight cancer
      specimens consisted of a mixture of a histologically predominant part and a small
      area with different histology. In these 18 tumors, the percentage of cells
      showing nuclear staining of Gli1 was higher in the undifferentiated-type part
      than in the differentiated-type part. Nuclear staining of Gli1 in primary tumors
      was positively correlated with lymph node metastasis. The Gli1 nuclear staining
      percentage of metastatic lymph nodes correlated closely with that of each primary
      carcinoma. Cyclopamine, a Hh pathway inhibitor, suppressed the growth of gastric
      cancer cells in vitro. CONCLUSIONS: The Hh pathway may be a useful therapeutic
      target for such as undifferentiated-type gastric cancer with lymph node
      metastasis.

PMID- 17192868
TI  - Influence of epidermal growth factor receptor (EGFR) gene mutations on the
      expression of EGFR, phosphoryl-Akt, and phosphoryl-MAPK, and on the prognosis of
      patients with non-small cell lung cancer.
AB  - BACKGROUND AND OBJECTIVES: In this paper we examined the influence of epidermal
      growth factor receptor (EGFR) gene mutations on EGFR expression, downstream
      mediators, and survival in patients with non-small cell lung cancer (NSCLC).
      METHODS: We retrospectively analyzed the tumors of 53 patients with completely
      resected pathological stage I-IIIA NSCLC for the presence of EGFR gene mutations,
      the expression of EGFR mRNA and protein, phosphoryl-Akt, and phosphoryl-mitogen
      activated protein kinase (MAPK) using immunostaining, and patients' prognosis.
      RESULTS: EGFR mutations were associated with elevations in EGFR mRNA (P = 0.004)
      and protein (P = 0.029) expression, but not with the expression of phosphoryl-Akt
      or phosphoryl-MAPK. The 5-year survival rate for all patients who exhibited an
      EGFR mutation was similar to those who were free of such mutations (71% vs. 56%,
      P = 0.252). However, the 5-year survival rate of patients with either a stage I
      adenocarcinoma or large cell carcinoma who had an EGFR mutation was significantly
      greater than for those who did not have such a mutation (92% vs. 57%, P = 0.037).
      CONCLUSIONS: EGFR gene mutations were significantly associated with higher EGFR
      expression, but not with p-Akt or p-MAPK status. In early stage NSCLC, the
      presence of an EGFR gene mutation bode well for the patient's prognosis.

PMID- 17192869
TI  - Expression of C-Myc mRNA in squamous cell carcinoma of the tongue.
AB  - BACKGROUND: The aim of this study was to evaluate clinical significance of C-myc
      mRNA in patients with tongue cancer. METHODS: C-myc mRNA expression was studied
      by RT-PCR in peripheral blood of 25 tongue cancer patients and 24 controls. C-myc
      protein expression was studied by immunohistochemistry. RESULTS: In tongue cancer
      patients, pretherapeutic C-myc mRNA expression was significantly higher as
      compared to controls. In tumor tissues, a trend of low expression of C-myc mRNA
      was noted as compared to pretherapeutic blood. The mean pretherapeutic C-myc mRNA
      level was lower in tobacco-users, in older patients, in keratinizing tumors, in
      tumors showed lymphocytic infiltration as well as in non-responders as compared
      to their respective counterparts. C-myc mRNA expression was lower in tumors
      showed lymphatic permeation and in patients with a habit of tobacco use. Further,
      low C-myc mRNA expression associated with poor prognosis. C-myc protein
      expression was noted in 72% of the tumors and an inverse correlation was noted
      between C-myc protein expression and disease stage. In early stage disease, an
      inverse correlation was noted while in advanced stage disease, a positive
      correlation was noted. CONCLUSION: In tongue cancer, downregulation of C-myc mRNA
      associated with advancement of the disease and worse prognosis.

PMID- 17192870
TI  - A cardiogastric fistula after gastric tube interposition. A case report and
      review of literature.
AB  - A patient is presented with massive hematemesis caused by a fistula between the
      left cardiac atrium and a gastric tube interposition, which was constructed after
      esophagectomy for esophageal cancer 3 years earlier.

PMID- 17192871
TI  - Differential apoptosis by gallotannin in human colon cancer cells with distinct
      p53 status.
AB  - Gallotannin (GT), a plant polyphenol, has shown anticarcinogenic activities in
      several animal models including colon cancer. In our previous study, we showed
      that GT inhibits 1,2-dimethylhydrazine-induced colonic aberrant crypt foci and
      tumors in Balb/c mice, thus supporting a role for GT as a chemopreventive agent
      in colon cancer. However, at the molecular level, GT's mechanism of
      chemoprevention is still unclear. In this study, we aim at identifying GT's
      potential molecular mechanisms of action in in vitro studies. We show that GT
      differentially inhibits the growth of two isogenic HCT-116 (p53+/+, p53-/-) human
      colon cancer cells versus normal human intestinal epithelial cells (FHs 74Int).
      DNA flow cytometric analysis showed that GT induced S-phase arrest in both HCT
      116 cell lines. Cell-cycle arrest in p53 (+/+) cells was associated with an
      increase in p53 protein levels and p21 transcript and protein levels. The
      inhibition of cell-cycle progression of HCT-116 p53 (+/+) cells by GT correlated
      with a reduction in the protein levels of cyclin D(1), pRb, and the Bax/Bcl-2
      ratio. Although GT did not induce apoptosis in p53 (+/+) cells, a significant
      induction of apoptosis was observed in p53 (-/-) cells as shown by TUNEL staining
      and flow cytometry analysis. Apoptosis induction in p53 (-/-) cells was
      associated with a significant increase in Bax/Bcl-2 protein levels. Our results
      demonstrate that GT inhibits the growth of HCT-116 colon cancer cells in a p53
      independent manner but exhibits differential sensitivity to apoptosis induction
      in HCT-116 cells with distinct p53 status.

PMID- 17192874
TI  - BCAR1 expression in prostate cancer: association with 16q23 LOH status, tumor
      progression and EGFR/KAI1 staining.
AB  - BACKGROUND: The 16q23 locus has been recently suggested in both breast and
      prostate cancer to contain a gene involved in disease progression. The breast
      cancer antiestrogen resistance 1 (BCAR1) gene, located at 16q23, contributes to
      many cellular processes including migration and survival, and interacts in vitro
      with the growth factor receptor EGFR and the metastasis suppressor KAI1. METHODS:
      BCAR1, EGFR, and KAI1 expression was studied by immunohistochemistry on a tissue
      microarray containing 100 localized prostate cancers (LPC), 15 hormone refractory
      prostate cancers (HRPC), and 15 lymph node metastasis (LNM). Forty eight of the
      LPC were also analyzed for 16q23 LOH status using microsatellite markers.
      RESULTS: BCAR1 staining was present in 25% of LPC, associated with higher Gleason
      score, and in 60% and 80% of, respectively, LNM and HRPC. BCAR1 expression was
      inversely correlated with 16q23 LOH status (P < 0.001), and was associated with
      high EGFR staining (P < 0.02), and negative KAI1 expression (P < 0.01).
      CONCLUSIONS: BCAR1 expression in LPC seems to be regulated at least in part by
      genetic events. The increased expression of BCAR1 with disease progression
      suggests a potential interest for both prognosis and treatment.

PMID- 17192873
TI  - The changes in coagulation profile and epidural catheter safety for living liver
      donors: a report on 6 years of our experience.
AB  - The use of epidural catheters has been a subject of active debate in living liver
      donors because of the possible postoperative coagulation derangement and the
      subsequent risk of epidural hematoma. The aim of this study was to evaluate the
      safety of epidural catheters in relation to the changes in coagulation profile
      based on a review of previously published literature and the results of our 360
      donors. In both the literature and in our cases, platelet count, prothrombin time
      (PT), and activated partial thromboplastin time (aPTT) in cases of heparin
      administration showed significant changes (P < 0.05), especially after right
      lobectomy. Platelet count reached its nadir on postoperative day (POD) 2-3, while
      PT and aPTT reached their peaks on POD 1-2 and at the end of the operation,
      respectively. In our donors, the ranges of platelet count, PT, and aPTT for the
      first 3 PODs were 54-359 x10/microL, 0.99-2.38 international normalized ratio
      (INR), and 25.9-300 seconds, respectively, and of note, 5 donors (1.4%) had a
      platelet count of <80 x 10/microL and 9 donors (2.5%) had a PT of >2.0 INR.
      Epidural catheterizations were performed in 242 donors, and the catheters were
      removed on POD 3-4 in 177 donors (73.1%). Mean (range) of platelet count, PT, and
      aPTT on the day of catheter removal were 168.4 +/- 42.9 (82-307) x 10/microL,
      1.33 +/- 0.18 (0.99-1.93) INR, and 40.9 +/- 4.8 (32.0-70.6) seconds,
      respectively. No epidural hematoma was observed in this study. In conclusion, the
      discreet use of epidural catheters in live liver donors, in spite of
      postoperative coagulation derangements, appears to be safe regardless of the type
      of hepatectomy performed.

PMID- 17192875
TI  - TGFBR3 loss and consequences in prostate cancer.
AB  - BACKGROUND: Resistance to transforming growth factor-beta (TGF-beta) is important
      in tumorigenesis. TGF-beta resistance mechanisms in prostate cancer are not well
      understood. METHODS: We have conducted a systematic analysis of TGF-beta pathway
      components with a meta-analysis of seven microarray studies using Oncomine and
      evaluated the results of TGFBR3 expression in prostate cell lines. Furthermore,
      we knocked down TGFBR3 in prostate epithelial cells and analyzed the consequences
      of TGFBR3 knockdown. RESULTS: We found that TGFBR3 is the TGF-beta component most
      commonly downregulated among localized human prostate cancer studies. TGFBR3
      knockdown led to focus formation and enhanced expression of CD133, a marker found
      on prostate cancer stem cells. DNA microarray analysis of TGFBR3 knockdown cells
      identified 101 genes regulated by TGFBR3. Seven of these genes show a
      corresponding decrease in clinical prostate cancer specimens, which include genes
      involved in prostate mass and vasculature. CONCLUSIONS: TGFBR3 downregulation is
      an important step in prostate tumorigenesis.

PMID- 17192876
TI  - Antibody array profiling reveals serum TSP-1 as a marker to distinguish benign
      from malignant prostatic disease.
AB  - BACKGROUND: Blood protein markers that provide more accurate or earlier diagnosis
      of prostate cancer should have a positive impact on prostate cancer treatment and
      management. METHODS: Serum samples from control subjects and patients with benign
      or malignant prostatic disease were analyzed on antibody arrays targeting
      multiple candidate prostate cancer markers and detected with two-color, rolling
      circle amplification (TC-RCA). The measurements of certain antibodies were
      validated using immunoblots, immunoprecipitation/mass spectrometry, and sandwich
      immunoassays. RESULTS: Several potential disease-associated protein alterations
      were uncovered. The most significant was thrombospondin-1, which was strongly
      elevated in patients with benign prostatic disease and repressed in patients with
      prostate cancer. Thrombospondin-1 levels did not correlate with prostate-specific
      antigen (PSA) levels and differentiated benign from malignant disease with 79%
      sensitivity and 81% specificity. CONCLUSIONS: The measurement of thrombospondin-1
      could be used to assist the decision to obtain a biopsy in men with suspected
      prostate cancer, which could lead to a reduction in the number of unnecessary
      prostatic biopsies.

PMID- 17192877
TI  - Plasma osteopontin in comparison with bone markers as indicator of bone
      metastasis and survival outcome in patients with prostate cancer.
AB  - BACKGROUND: The study was undertaken to evaluate the diagnostic and prognostic
      value of plasma osteopontin (OPN) in comparison to bone markers as well as the
      relationships between the markers and clinico-pathological factors in prostate
      cancer (PCa) patients. METHODS: OPN and the bone markers carboxyterminal
      telopeptide of type I collagen, bone-specific alkaline phosphatase (bALP), and
      aminoterminal-propeptide of type I procollagen (PINP) were measured in 90 PCa
      patients with and without bone metastases, 35 patients with benign prostatic
      hyperplasia, and 29 healthy men. RESULTS: OPN and bone markers were significantly
      elevated in patients with bone metastases compared to the other groups.
      Significant correlations were found between all four-bone markers (r(s) = 0.43
      0.79, all P < 0.01). OPN correlated with tumor grade (r(s) = 0.23, P < 0.05). In
      receiver-operating characteristics (ROC) analyses, OPN and bone markers were
      effective in distinguishing PCa patients with and without bone metastases showing
      areas under the curve (AUC) between 0.80 and 0.88 (all P < 0.001). OPN had an AUC
      of 0.85 that increased in combination with bALP up to 0.93 providing at the point
      with the highest diagnostic accuracy both a sensitivity and specificity of about
      90%. Kaplan-Meier analyses and Cox proportional hazards regression models showed
      decreased survival of patients with high OPN and bone marker levels, while only
      high OPN and PINP were independent negative prognostic factors for PCa-related
      death. CONCLUSIONS: OPN alone or in combination with bone markers is useful as
      diagnostic marker in the detection of bone metastases and as prognosticator in
      the survival prediction in PCa patients.

PMID- 17192879
TI  - Changes in steroid receptors and proteoglycan expression in the guinea pig
      prostate stroma during puberty and hormone manipulation.
AB  - BACKGROUND: Proteoglycans are structural and informational molecules important
      during embryogenesis and organ maturation. Maturation of the prostate is
      influenced by androgens and estrogens, but changes in the relative spatiotemporal
      expression of steroid receptors and proteoglycans during hormonal change are
      unexplored. METHODS: Guinea pig prostate was used to define hormone-induced
      changes in the expression of androgen (AR) and estrogen (ER(alpha)) receptors,
      chondroitin sulfate (CS) glycosaminoglycan and core proteins of versican and
      syndecan-1. Tissue locations of AR, ER(alpha), CS and the proteoglycans versican
      and syndecan-1 were determined by immunohistochemistry. Cellular content of
      ER(alpha) and syndecan-1 was assessed visually. Versican, CS56 epitope, and AR
      were quantified by image analysis. RESULTS: AR expression within prostate
      epithelial and stromal cell nuclei decreased following castration and increased
      following treatment of castrate animals with dihydrotestosterone (DHT). ER(alpha)
      expression was restricted to prostate stromal cell nuclei and decreased during
      puberty, and following treatment of castrate animals with DHT. Versican was
      present in periacinar stroma immediately peripheral to basal epithelial cells,
      fibromuscular stromal tissue bands surrounding acinar units, and loose
      fibrovascular connective tissue interspersed between individual acini. Versican
      and native CS expression decreased (>10-fold) in periacinar stroma during puberty
      and following administration of DHT to castrated animals. Expression of syndecan
      1 was restricted to fibromuscular cells of prostate stroma, and remained constant
      during puberty and hormone manipulation. CONCLUSIONS: ER(alpha), versican core
      protein and CS side chain epitopes are negatively regulated in prostate stromal
      tissue by DHT, whilst AR levels are positively regulated.

PMID- 17192878
TI  - Identification of a novel prostate cancer-associated tumor antigen.
AB  - BACKGROUND: The identification of antigens that distinguish cancer cells from
      normal cells is of major importance for the definition of therapeutic targets in
      human malignancies. Using sera from cancer patients, we have previously reported
      on the identification of immunologically recognized proteins that belong to the
      family of cancer testis antigens (CTAs). METHODS: A normal testicular cDNA
      library was screened with pooled allogeneic sera from patients with prostate
      cancer using a modified SEREX approach. Subsequently we have identified and
      characterized a novel antigen, T21, with an expression pattern similar to that of
      CTAs. mRNA expression of T21 was determined using a panel of whole tissues and
      prostate cell lines using Q-RT-PCR. For laser microdissection, fresh prostate
      cancer and benign tissue was obtained using our novel validated harvesting
      technique. Protein expression and cellular localization of T21 were assessed in
      prostate cell lines using Western blotting, confocal microscopy and flow
      cytometry. RESULTS: T21 showed tissue-restricted mRNA expression in gastric,
      kidney and prostate cancers, and in normal testis and prostate tissues. Following
      laser microdissection, T21 was significantly over-expressed in malignant compared
      to benign prostatic epithelium. We have demonstrated expression of T21 at the
      protein level and confocal microscopy on PC3 cells probed with a T21-monospecific
      antibody revealed cytoplasmic localization of T21 protein. CONCLUSIONS: The
      highly restricted expression pattern of T21 makes it an attractive vaccine target
      for prostate cancer. Several CTAs reportedly induce cytotoxic T-lymphocyte
      responses, therefore it is reasonable to assume that T21 will be a valuable
      target for cancer immunotherapy.

PMID- 17192880
TI  - Germline copy number polymorphisms involving larger than 100 kb are uncommon in
      normal subjects.
AB  - BACKGROUND: Recent studies using ROMA and Array-CGH suggest that germline copy
      number polymorphisms (CNPs) involving >100 kb are common in humans. METHODS: In
      this study, we used the Affymetrix GeneChip 100K single nucleotide polymorphisms
      (SNP) mapping panel to further examine the type and frequency of germline CNPs in
      the genome. By utilizing the allele intensity data generated while genotyping
      approximately 116,000 SNPs among 23 subjects from 4 families, we were able to
      detect multiple CNPs. RESULTS: However, in contrast to several previous studies,
      we found that CNPs >100 kb are rare in the genome but CNPs involving 100s-1,000s
      of base pairs are more common. CONCLUSIONS: We have demonstrated the utility of
      this approach, which has an important advantage over other methods because it is
      able to simultaneously assess both CNPs and SNPs, and therefore has great
      potential in genetic association studies of common diseases.

PMID- 17192882
TI  - More tools, new strategies: Enlarging the therapeutic scope for the patient with
      liver metastases from colorectal cancer.

PMID- 17192881
TI  - Silkclasy: a simple way for liver transection during anatomic hepatectomies.
AB  - BACKGROUND: Parenchymal transection is the most important step of liver
      resection, and during this phase, blood loss may lead to morbidity and mortality.
      Liver parenchyma can be transected by different ways such as finger fracture,
      clamp crushing, or instrument-based techniques. METHODS: A simple and cost
      efficient method has been developed for liver transection using a technique based
      on silk crushing of the liver substance. RESULTS: We have successfully employed
      this technique in 278 consecutive liver resections from July 2001 to March 2006.
      The average duration of hepatic transection varied according to the type of liver
      resection: 22 min (range 15-42), 19 min (range 11-37), and 12 min (range 7-21)
      for right hepatectomy, left hepatectomy, and bisegmentectomy 2-3, respectively.
      The mean transection speed was 6.9 +/- 2.3 cm(2)/min. Blood transfusions were
      necessary in 42 patients (15.1%), and there were three operative deaths (1.1%).
      Morbidity rate was 20.9% (58 patients). CONCLUSIONS: This technique allows a safe
      and quick liver transection without the use of expensive hemostatic devices, and
      also precludes the use of inflow occlusion maneuvers. We recommend the use of
      this technique in centers with low economic resources.

PMID- 17192884
TI  - A cancer staging perspective: the value of anatomical staging.

PMID- 17192883
TI  - The current status of breast cancer chemoprevention: a star is born.

PMID- 17192885
TI  - TNM staging is obsolete.

PMID- 17192886
TI  - Cytokines and cancer development.

PMID- 17192887
TI  - Long term administration of granulocyte-macrophage colony stimulating factor
      decreases development of 1-2 dimethylhydrazine-induced colon cancer in rats.
AB  - BACKGROUND AND OBJECTIVES: The antitumoral activities of granulocyte-macrophage
      colony stimulating factor (GM-CSF) were shown earlier. In this study, the effects
      of GM-CSF were investigated on colon cancer induced by 18 weeks of 1-2
      dimethylhydrazine (DMH) administration in rats. METHODS: Four groups received
      subcutaneous saline (n = 20), 15 mg/kg DMH (n = 30), DMH +6 microg/kg GM-CSF (n =
      30), and DMH +12 microg/kg (n = 30) GM-CSF. RESULTS: The average number of tumors
      (2.8 vs. 1.5) and mean tumor volume (179 +/- 36 vs. 27 +/- 9 mm(3); means +/-
      SEM) were reduced in DMH + GM-CSF groups as compared to the DMH group (n = 30, P
      < 0.01). DMH-induced enhancement of free radicals and lipid peroxidation were
      decreased in DMH + GM-CSF group (n = 8-12, P < 0.05). The magnitude of DMH
      induced alterations in superoxide dismutase (SOD) and glutathione peroxidase
      (GPx) activities was lowered in the DMH + GM-CSF group (n = 12-16, P < 0.05). DMH
      induced increases in the total nitrite/nitrate levels and the nitric oxide
      synthase (NOS) activity (n = 10-12, P < 0.05) were also reduced in the DMH + GM
      CSF group (n = 8-9, P < 0.05). CONCLUSIONS: The results indicate that GM-CSF
      inhibits the development of DMH-induced colon cancer in rats and suggest that
      inhibition of oxidative stress and NO pathway are involved in the observed
      antitumoral effects.

PMID- 17192888
TI  - Balance between endoscopic and genetic information in the choice of ileorectal
      anastomosis for familial adenomatous polyposis.
AB  - BACKGROUND AND OBJECTIVES: The number of rectal polyps and the site of mutations
      in the APC (Adenomatous polyposis coli) gene have been used to guide the surgical
      management in patients with familial adenomatous polyposis (FAP). The aim of this
      study is to assess the utility of the APC mutation screening compared to the
      degree of the rectal polyposis in surgical decision making. METHODS: The post
      surgical courses of 25 patients submitted to subtotal colectomy with ileorectal
      anastomosis (IRA) were reviewed. Preservation of the rectum was prospectively
      decided on the basis of well-defined endoscopic criteria. The number of rectal
      polyps was assessed preoperatively and every 6-12 months. APC gene was screened
      for mutations by heteroduplex analysis, single strand conformation polymorphism,
      in vitro synthesized protein (IVSP), and DNA sequencing. Patients negative for
      APC mutations were tested for MYH mutations. RESULTS: On the basis of
      preoperative polyp rectal count we categorized patients as follows: Group I, 5 or
      fewer adenomas; Group II, 6-9 adenomas; Group III, 10 or more adenomas. After a
      follow-up ranging from 12 to 225 months we have observed a significant difference
      of recurrent rectal adenomas between Groups I-II versus III. No difference was
      detected among patients of Group I and II. The mean number of
      adenomas/year/patient was 0.67, 1.62, and 9.29 for Group I, II, and III,
      respectively. Carpeting polyposis of the rectal stump developed in three patients
      with APC mutation at codon 1309 and two of them needed later proctectomy. Diffuse
      rectal polyposis was observed in one patient with mutation at exon 9 who had 10
      small polyps at time of surgery. Mutation at the 5'-end of APC (codons 144-232),
      mutation of MYH and unknown APC or MYH mutation were correlated with a low number
      of polyps both at presentation and follow-up. No IRA patients developed rectal
      cancer. CONCLUSIONS: In our experience fewer than 10 rectal polyps at
      presentation can predict a favorable outcome after IRA. Identification of
      specific germ-line APC or MYH mutation can address the choice of surgical
      treatment.

PMID- 17192889
TI  - In a MELD-based economy, how can we fight off inflation?

PMID- 17192890
TI  - Is there a link between hepatitis C virus and new onset of diabetes mellitus
      after liver transplantation?

PMID- 17192891
TI  - Effect of side and size of graft on surgical outcomes of adult-to-adult live
      donor liver transplantation.
AB  - By virtue of size, the right liver graft has become the workhorse of adult-to
      adult live donor liver transplantation (ALDLT). Although favorable results of
      left liver ALDLT have also been reported, a head-to-head comparison of these 2
      graft types both containing the middle hepatic vein had not been made. In this
      study, we compared the outcomes of 29 right liver and 16 left liver ALDLTs of
      comparable graft weight to recipient estimated standard liver volume ratio
      (GW/ESLV, 36.9% and 36.4%, respectively). All liver grafts contained the middle
      hepatic vein. The Model for End-Stage Liver Disease (MELD) score and urgency for
      transplantation of both groups were similar. Postoperatively, left liver donors
      had significantly lower international normalized ratios and serum total bilirubin
      levels and no complications. Although the rate of return of international
      normalized ratios for recipients of both groups were comparable, left liver
      recipients had significantly higher serum total bilirubin and serum
      aminotransferase levels. Intensive care unit stay of the left liver recipients
      was longer than that of the right liver recipients (8.5 days versus 4 days, P =
      0.007). Hospital mortality was 6.9% (2/29) for the right liver group and 18.8%
      (3/16) for the left liver group (P = 0.330). Safety profile of donor left
      hepatectomy was higher. However, despite similar GW/ESLV, the more arduous
      recovery and higher mortality rate of left liver recipients raise the caution of
      assuming the gram-to-gram equivalence of right and left liver grafts.

PMID- 17192892
TI  - Reduced oxygen concentration improves the developmental competence of mouse
      oocytes following in vitro maturation.
AB  - Reduced atmospheric oxygen concentration is beneficial to embryo development;
      however, optimal oxygen concentration for oocyte maturation remains undetermined.
      Likewise, there is no consensus of appropriate medium supplementation during
      maturation. The objective of this study was to determine whether oxygen tension
      (20% or 5% O2) and epidermal growth factor (EGF) affect oocyte metabolism and
      subsequent embryo development. Cumulus-oocyte complexes (COCs) were collected
      from 28-day-old equine chorionic gonadotropin (eCG) primed or unprimed F1
      (C57BL/6xCBA) mice. COCs were matured in defined medium in one of four groups:
      20% O2, 20% O2 + EGF, 5% O2, 5% O2 + EGF. In vivo matured COCs were also
      collected for analysis. COCs from unprimed mice, matured in 5% O2 +/- EGF or 20%
      O2 + EGF had higher metabolic rates than COCs matured in 20% O2 (P < 0.05). COCs
      from primed mice had higher metabolic rates when matured in the presence of EGF,
      regardless of oxygen tension (P < 0.01). Oxygen uptake and mitochondrial membrane
      potential were higher for in vivo matured oocytes and oocytes matured under 5% O2
      compared to oocytes matured under 20% O2 (P < 0.05). Blastocyst formation was not
      different between maturation groups (primed or unprimed); however, embryo cell
      numbers were 20-45% significantly higher when COCs were matured at 5% O2 (P <
      0.05). Results suggest that oocytes matured in physiological concentrations of
      oxygen have improved development and metabolic activity, more closely resembling
      in vivo maturation. These findings have implications for oocyte maturation in
      both clinical and research laboratories.

PMID- 17192893
TI  - Effect of 5-haplotype of dysbindin gene (DTNBP1) polymorphisms for the
      susceptibility to bipolar I disorder.
AB  - We investigated a possible association between dysbindin gene (DTNBP1) variants
      and bipolar I disorder (BID). Five SNPs within DTNBP1 (rs3213207, rs1011313,
      rs2005976, rs760761, and rs2619522) were genotyped for 151 patients with BID and
      478 controls. We observed a significant protective association of the haplotype A
      C-G-T-A (all SNPs, P = 0.00016) and particularly G-T-A (the last three SNP, P =
      0.00007) within DTNBP1 variants investigated. Single marker and subgroup (e.g.,
      psychotic features, age at onset, family history, etc.) analyses showed no
      significant association. Although the association was due to a small number of
      subjects, specific DTNBP1 haplotypes, previously associated with schizophrenia,
      may be also associated with BID. Adequately powered studies from different
      ethnicities will be necessary to confirm our findings.

PMID- 17192894
TI  - Sensory gating and alpha-7 nicotinic receptor gene allelic variants in
      schizoaffective disorder, bipolar type.
AB  - OBJECTIVES: Single nucleotide allelic variants in the promoter region of the
      chromosome 15 alpha-7 acetylcholine nicotinic receptor gene (CHRNA7) are
      associated with both schizophrenia and the P50 auditory evoked potential sensory
      gating deficit. The purpose of this study was to determine if CHRNA7 promoter
      allelic variants are also associated with abnormal P50 ratios in persons with
      schizoaffective disorder, bipolar type. METHODS: P50 auditory evoked potentials
      were recorded in a paired stimulus paradigm in 17 subjects with schizoaffective
      disorder, bipolar type. The P50 test to conditioning ratio was used as the
      measure of sensory gating. Mutation screening of the CHRNA7 promoter region was
      performed on the subjects' DNA samples. Comparisons to previously obtained data
      from persons with schizophrenia and controls were made. RESULTS: Subjects with
      schizophrenia, regardless of allele status, had an abnormal mean P50 ratio.
      Subjects with schizoaffective disorder, bipolar type and a variant allele had an
      abnormal mean P50 ratio, whereas those schizoaffective subjects with the common
      alleles had a normal mean P50 ratio. Normal control subjects had a normal mean
      ratio, but controls with variant alleles had higher P50 ratios. CONCLUSIONS: In
      persons with bipolar type schizoaffective disorder, CHRNA7 promoter region
      allelic variants are linked to the capacity to inhibit the P50 auditory evoked
      potential and thus are associated with a type of illness genetically and
      biologically more similar to schizophrenia.

PMID- 17192895
TI  - Absence of the Arg441His polymorphism in the tryptophan hydroxylase 2 gene in
      adults with anxiety disorders and depression.

PMID- 17192897
TI  - Excess of cancers in Europe: a study of eleven major cancers amenable to
      lifestyle change.
AB  - Worldwide an estimated 11 million cancer cases were diagnosed in 2002, one
      quarter being in Europe. We estimated the potential in avoidable numbers and
      proportions of 11 cancers amenable to prevention (cancers of the oral cavity,
      oesophagus, stomach, colorectal, pancreas, laryngeal, lung, female breast,
      endometrium, kidney and bladder) in 28 European countries. We assumed that the
      aggregated rate of 3 countries with lowest incidence to be attainable throughout
      Europe. The difference between the age- and gender-specific national cancer
      incidence rates and the lowest rate observed in 2002 was determined and defined
      as "avoidable." Of the 1.4 million adult cases of selected cancers and countries
      within our study, 363,000 (59%) cancers in males and 326,000 (45%) cancers in
      females were hypothetically avoidable. Among men, the proportion was largest in
      Hungary (77%) and among women, in Belgium (54%). Assuming that differences in
      cancer incidence are not attributable to genetic susceptibility or diagnostic
      activity, about 50% of all cases of these 11 cancers could be potentially
      avoided, especially by decreased smoking among men. Interventions directed at
      reducing smoking, obesity and alcohol use as well as increasing physical activity
      and fruit and vegetable intake are necessary to attain lower incidence rates. It
      is important to recognize that the actual preventable cancer by eliminating
      currently known risk factors is somewhat less than we have estimated.

PMID- 17192896
TI  - Accurate discrimination of pancreatic ductal adenocarcinoma and chronic
      pancreatitis using multimarker expression data and samples obtained by minimally
      invasive fine needle aspiration.
AB  - To augment cytological diagnosis of pancreatic ductal adenocarcinoma (PDAC) in
      tissue samples obtained by minimally invasive endoscopic ultrasound-guided fine
      needle aspiration, we investigated whether a small set of molecular markers could
      accurately distinguish PDAC from chronic pancreatitis (CP). Expression levels of
      29 genes were first determined by quantitative real-time RT-PCR in a training set
      of tissues in which the final diagnosis was PDAC (n=20) or CP (n=10). Using
      receiver operator characteristic curve analysis, we determined that the single
      gene with the highest diagnostic accuracy for discrimination of CP vs. PDAC in
      the training study was urokinase plasminogen activator receptor (UPAR; AUC value
      = 0.895, 95% CI=0.728-0.976). In the set of test tissues (n=14), the accuracy of
      UPAR decreased to 79%. However, we observed that the addition of 6 genes (EPCAM2,
      MAL2, CEA5, CEA6, MSLN and TRIM29; referred to as the 6-gene classifier) to UPAR
      resulted in high accuracy in both training and testing sets. Excluding 3 samples
      (out of 44; 7%) for which results of the UPAR/6-gene classifier were "undefined,"
      the accuracy of the UPAR/6-gene classifier was 100% in training samples (n=29),
      92% in 12 test samples (p=0.004 that results were randomly generated; p=0.046
      that the UPAR/6-gene classifier was comparable to UPAR alone; chi2 test), 100% in
      3 samples for which the initial cytological diagnosis was "suspicious" and 98%
      (40/41) overall. Our results provide evidence that molecular marker expression
      data can be used to augment cytological analysis.

PMID- 17192898
TI  - Parity, tubal sterilization, hysterectomy and risk of primary fallopian tube
      carcinoma in Finland, 1975-2004.
AB  - We studied the possible relationship among parity, female sterilization,
      hysterectomy and the risk of primary fallopian tube carcinoma (PFTC) in a case
      control study in Finland in cases occurring between 1975 and 2004. A total of 573
      PFTC cases were identified from the Finnish Cancer Registry, and 10 age-matched
      controls per case were randomly selected from the Finnish Central Population
      Registry. In multivariate analysis (including 189 PFTC cases and 1764 controls)
      parity was protective: the odds ratio (OR) for 1-2 deliveries was 0.63 (95% CI
      0.44-0.91) and for > or =3 deliveries, 0.32 (95% CI 0.19-0.52). The OR for
      sterilization was 0.74 (95% CI 0.42-1.30) and for hysterectomy 1.27 (95% CI 0.73
      2.21). Our findings suggest a possible hormonal background as regards the
      development of PFTC.

PMID- 17192899
TI  - Lack of BK virus DNA sequences in most transitional-cell carcinomas of the
      bladder.
AB  - BK virus (BKV), a common human polyomavirus infection latent in the kidneys, can
      reactivate with immunosuppression to cause renal disease. Some have suggested
      that BKV may contribute to the development of bladder cancer, and BKV sequences
      have been reported from bladder tumors. To further examine the role of BKV in
      human bladder cancer, a series of bladder tumors was investigated for BKV genomic
      sequences. Fresh-frozen specimens from 76 transitional cell carcinoma tissues and
      46 paired adjacent normal urothelial tissues archived at the H. Lee Moffitt
      Cancer Center were studied. All tissues were histopathologically reviewed. DNA
      extracted from the tissues was tested by quantitative real-time polymerase chain
      reaction (QPCR) assays to detect BKV DNA sequences in the VP1 coding region.
      Amplification of ERV-3 was conducted separately to quantify cell copy number.
      Conventional PCR targeting the BKV T-antigen (T-Ag) coding region and
      immunohistochemistry for BKV T-Ag were also conducted on all tissues that tested
      positive for BKV by QPCR. Seventy-three bladder tumors yielded >/=3,000 copies of
      ERV-3, 4 (5.5%) of which tested positive for BKV with average copy numbers of
      7.9, 15.8, 0.4 and 0.3 per 1,000 cells. Paired normal tissue was available for 2
      of these BKV-positive tumors, 1 of which was BKV-positive (14.6 copies/1,000
      cells). No other normal tissues were BKV-positive by QPCR. The 6 BKV-positive
      tissues by QPCR were also positive by conventional PCR, but all stained negative
      for BKV T-Ag by immunohistochemistry. BKV is unlikely to be involved in the
      etiology of most bladder tumors.

PMID- 17192900
TI  - Selective inhibition of PED protein expression sensitizes B-cell chronic
      lymphocytic leukaemia cells to TRAIL-induced apoptosis.
AB  - B-cell chronic lymphocytic leukaemia (B-CLL) cells fail to undergo apoptosis. The
      mechanism underlying this resistance to cell death is still largely unknown.
      Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively
      kills tumour cells but not normal cells, and thus represents an attractive tool
      for the treatment of cancer. Unfortunately, lymphocytes from B-CLL patients are
      resistant to TRAIL-mediated apoptosis. Thus, we aimed to study the involvement of
      PED, a DED-family member with a broad antiapoptotic action, in this resistance.
      We demonstrate that B lymphocytes obtained from patients with B-CLL express high
      levels of PED. Treatment of B-CLL cells with specific PED antisense
      oligonucleotides, a protein synthesis inhibitor or HDAC inhibitors, induced a
      significant downregulation of PED and sensitized these cells to TRAIL-induced
      cell death. These findings suggest a direct involvement of PED in resistance to
      TRAIL-induced apoptosis in B-CLL. It also identifies this DED-family member as a
      potential therapeutic target for this form of leukaemia.

PMID- 17192901
TI  - Flavonoids and risk of squamous cell esophageal cancer.
AB  - The relation between 5 classes of flavonoids (flavanones, flavan-3-ols,
      flavonols, flavones and anthocyanidines) and esophageal cancer was investigated
      using data from a case-control study conducted between 1992 and 1997 in 3 areas
      of northern Italy. The study included 304 cases (275 men, 29 women) with a first
      diagnosis of squamous-cell carcinoma of the esophagus and 743 controls (593 men,
      150 women) with no history of cancer, admitted for acute illnesses, unrelated to
      tobacco and alcohol consumption, to major hospitals of the areas under
      surveillance. Dietary habits were investigated using a validated food frequency
      questionnaire. Odds ratios (ORs) and 95% confidence intervals (CI) were computed
      after allowance for age, sex, study centre, years of education, alcohol drinking,
      tobacco smoking, body mass index and energy intake. An inverse association
      emerged between flavanone intake and esophageal cancer risk (OR=0.38 for the
      highest vs. the lowest quintile, 95% CI=0.23-0.66). The inverse relation between
      flavanones and esophageal cancer tended to be stronger in those who drank >or=6
      drinks/day. In conclusion, this study suggests that flavanone intake is inversely
      associated with esophageal cancer risk and may account, with vitamin C, for the
      protective effect of fruit, especially citrus fruit, on esophageal cancer.

PMID- 17192903
TI  - HLA and outcome in living donor liver transplantation in primary biliary
      cirrhosis: a new piece in the jigsaw?

PMID- 17192902
TI  - The impact of epidermal growth factor receptor gene status on gefitinib-treated
      Japanese patients with non-small-cell lung cancer.
AB  - We investigated the relationships between genetic factors and clinical outcome in
      Japanese non-small-cell lung cancer (NSCLC) patients treated with gefitinib.
      Ninety-eight NSCLC patients who had been treated with gefitinib, were screened
      for mutations in epidermal growth factor receptor (EGFR) exons 18-21, KRAS exon2,
      and polymorphisms including the CA simple sequence repeat in intron1 (CA-SSR1)
      and single nucleotide polymorphisms in the promoter region (-216G/T and -191C/A),
      using a PCR-based assay and direct sequencing. The EGFR copy number status was
      also evaluated using a fluorescence in situ hybridization assay. EGFR and KRAS
      mutations were found in 38 (38.8%) and 8 (8.2%) of the 98 patients, respectively.
      A high EGFR copy number status was identified in 31 (41.3%) of the 75 assessable
      patients. Drug-sensitive EGFR mutations limited to exon19 deletions and L858R
      were independent predictive factors of a stronger sensitivity to gefitinib (p =
      0.0002), the overall survival (OS) (p = 0.0036), and prolonged progression-free
      survival (PFS) (p < 0.0001). The EGFR copy number status was not related to a
      sensitivity to gefitinib and prolonged OS and PFS. Regarding polymorphisms,
      patients with a short CA-SSR1 showed a prolonged OS as compared with those with a
      long length in patients with a drug-sensitive EGFR mutation, although this
      difference was not significant (p = 0.13). Thus, drug-sensitive EGFR mutations
      predict a favorable clinical outcome and a high EGFR copy number may not be
      related to clinical benefits in gefitinib-treated Japanese patients with NSCLC.
      Our findings also suggest that the CA-SSR1 length may influence the clinical
      outcome in patients with a drug-sensitive EGFR mutation.

PMID- 17192904
TI  - Adoptive transfer of immunity to HBV in liver transplant patients: a step forward
      toward the proof of concept for therapeutic vaccination or a transient
      immunologic phenomenon?

PMID- 17192905
TI  - Living donor liver transplantation and hepatitis C: lessons from the learning
      curve?

PMID- 17192906
TI  - Immunosuppression with calcineurin inhibitors with respect to the outcome of HCV
      recurrence after liver transplantation: results of a meta-analysis.
AB  - A controversy exists over whether the outcome of a hepatitis C virus (HCV)
      infection-related liver transplant differs based on the calcineurin inhibitor
      (CNI) used. We have performed a systematic review and a subsequent meta-analysis
      evaluating tacrolimus (Tac)-based vs. cyclosporine A-based immunosuppression in
      HCV-infected liver transplant recipients. Searches were conducted to locate
      randomized controlled trials comparing Tac vs. cyclosporine A. Data on HCV liver
      transplant recipients were obtained, independently of whether the study was
      specifically designed for patients with this disease or not. A fixed effects
      model was used for statistical pooling of the relative risks (RR) for the
      different outcomes. A total of 5 articles (366 patients) fulfilled the inclusion
      criteria. Statistically significant differences between Tac-based vs.
      cyclosporine A-based therapies were not found for mortality (P = 0.11; RR = 0.72;
      95% confidence interval [CI], 0.49-1.08), graft survival (P = 0.37; RR = 0.86;
      95% CI, 0.61-1.21), biopsy-proven acute rejection (P = 0.65; RR = 0.91; 95% CI,
      0.61-1.36), corticoresistant acute rejection (P = 0.26; RR = 2.25; 95% CI, 0.55
      9.29), and fibrosing cholestatic hepatitis (P = 0.92; RR = 0.96; 95% CI, 0.41
      2.26). In 1 study, no differences were detected regarding severe fibrosis at 1
      yr. In conclusion, patient and graft survivals in HCV-positive liver transplant
      patients are similar independently of the CNI selected as basic
      immunosuppressant. Unfortunately, data on the severity of recurrence and effect
      on viremia are scarce. Well-designed randomized prospective studies are needed to
      determine whether there are differences between the 2 CNIs regarding these
      specific variables.

PMID- 17192907
TI  - Wide gene expression profiling of ischemia-reperfusion injury in human liver
      transplantation.
AB  - Ischemia-reperfusion injury (IRI) causes up to 10% of early liver failures in
      humans and can lead to a higher incidence of acute and chronic rejection. So far,
      very few studies have investigated wide gene expression profiles associated with
      the IRI process. The discovery of novel genes activated by IRI might lead to the
      identification of potential target genes for the prevention or treatment of the
      injury. In our study, we compared gene expression levels in reperfused livers (RL
      group) vs. the basal values before retrieval from the donor (basal liver [BL]
      group) using oligonucleotide array technology. We examined 10 biopsies from 5
      livers, analyzing approximately 33,000 genes represented on the Affymetrix HG
      U133APlus 2.0 oligonucleotide arrays (Affymetrix, Santa Clara, CA). About 13,000
      individual genes were considered expressed in at least 1 condition. A total of
      795 genes whose expression is significantly modified by ischemia-reperfusion in
      human liver transplantation were identified in this study. Some of them are
      likely to be completely activated by IRI, as they are not expressed in basal
      livers. The supervised gene expression analysis revealed that at least 12% of the
      genes involved in the apoptotic process, 12.5% of the genes involved in
      inflammatory processes, and 22.5% of the genes encoding for heat shock proteins
      are differentially expressed in RL samples vs. BL samples. Furthermore, IRI
      induces the upregulation of some genes' coding for adhesion molecules and
      integrins. In conclusion, we have identified a relevant amount of early genes
      regulated in the human liver after 7-9 hours of cold ischemia and 2 hours from
      reperfusion, many of them not having been described before in this process. Their
      analyses may help us to better understand the pathophysiology of IRI and to
      characterize potential target genes for the prevention or treatment of the liver
      injury in order to increase the number of patients that successfully undergo
      transplantation.

PMID- 17192909
TI  - Exploring the bidirectional interactions between human cytomegalovirus and
      hepatitis C virus replication after liver transplantation.
AB  - Recurrence of Hepatitis C (HCV) post-liver transplantation (LT) is universal and
      its course is more aggressive than in immunocompetent individuals. Human
      cytomegalovirus (CMV) infection is a common post-LT infection and has
      immunomodulatory effects that could adversely affect the outcome of HCV. To date,
      the effect of HCV replication on the dynamics of CMV have not been investigated.
      From 2000 to 2004, a cohort of 69 HCV-infected liver transplant recipients and
      188 HCV-negative liver transplant recipients (NON-HCV cohort) were monitored for
      CMV infection twice weekly by CMV polymerase chain reaction (PCR) with preemptive
      therapy initiated after 2 consecutive positive results. None of the patients
      received CMV prophylaxis. A subset of 18 HCV-infected patients had their HCV
      viral load monitored regularly post-LT by quantitative PCR. CMV DNAemia (>200
      genomes/mL blood) did not influence the level of HCV replication within 150 days
      posttransplantation or the stage of liver fibrosis in liver biopsies at 1 yr post
      LT. There were no differences in the incidence of CMV DNAemia or replication
      dynamics in the HCV cohort compared to the NON-HCV cohort. In conclusion, short
      term CMV viremia does not enhance the replication of HCV after LT, while HCV
      replication does not alter the replication dynamics of CMV.

PMID- 17192910
TI  - Promoter hypermethylation of GSTP1, AR, and 14-3-3sigma in serum of prostate
      cancer patients and its clinical relevance.
AB  - OBJECTIVE: Hypermethylation of tumor suppressor genes (TSG) is thought to play an
      important role in tumorigenesis of prostate cancer. The main focus of research
      was the detection of TSG hypermethylation in cancer tissue. Our aim was to
      evaluate the feasibility of detection of hypermethylated genes in serum of
      prostate cancer patients and its correlation with clinicopathological parameters.
      METHODS: One hundred twenty-five serum samples from 62 patients with hormone
      refractory prostate cancer (HRPC), 14 patients with early disease, and 49 healthy
      controls were examined. After DNA extraction and sodium-bisulfite treatment,
      conventional methylation-specific PCR (MSP) was performed for glutathione S
      transferase P1 (GSTP1), androgen receptor (AR), and 14-3-3sigma. RESULTS: In
      serum of HRCP patients, frequency of GSTP1, AR, and 14-3-3sigma hypermethylation
      was 32.2, 40.3, and 86.6%, respectively. In serum of patients with early disease
      frequency of GSTP1, AR, and 14-3-3sigma, hypermethylation was 21.4, 35.7, and
      85.7%. In healthy controls, frequency of GSTP1, AR, and 14-3-3sigma
      hypermethylation was 0, 26.5, and 55.1%, respectively. There was a significant
      increase of frequency of TSG hypermethylation for GSTP1 and 14-3-3sigma in HRPC
      patients, in comparison with healthy controls. GSTP1 hypermethylation in HRPC
      patients was significantly correlated with differentiation of cancer and
      metastatic disease. CONCLUSIONS: Hypermethylation of TSG can be detected in serum
      of prostate cancer patients. Some hypermethylated TSG can be detected in serum of
      healthy controls. GSTP1 was not detectable in controls and correlated
      significantly with Gleason score and stage of disease. Therefore, this gene may
      be a promising new tool in prostate cancer diagnosis.

PMID- 17192912
TI  - The value of different screening tests in predicting prostate biopsy outcome in
      screening for prostate cancer data from a multicenter study (ERSPC).
AB  - BACKGROUND: Although serum PSA testing is widely used as a screening test for
      prostate cancer (PC), it is known that it is not specific for PC. The study
      described here focuses on the value of screening tests next to PSA in identifying
      men with an elevated risk of having PC and the differences between three centers
      of the European Randomised study of Screening for Prostate Cancer (ERSPC).
      METHODS: The study population consists of 2,483 men with a PSA > or =4.0 ng/ml,
      all biopsied. We assessed data on age, serum PSA level at initial and repeat
      screening, prostate volume, number of positive DRE and TRUS findings, number of
      previous negative biopsies, and PPV of the three centers and overall. Using
      logistic regression analysis, predictors for biopsy outcome at repeat screening
      in men with a PSA value > or =4.0 ng/ml were determined on the complete dataset
      and per center. RESULTS: In 2,483 men biopsied, 665 cancers were detected (PPV =
      26.8%). Data show that all predictors except prostate volume loose their
      predictive value in men previously biopsied. In men not previously biopsied, the
      predictive value of DRE and TRUS vary considerably among the three centers.
      CONCLUSIONS: Looking at the differences in the predictive value of screening
      tests in three "comparable" centers, generasibility is not as straightforward as
      it seems. Using a nomogram for predictive purposes developed elsewhere will
      require a thorough knowledge of the patient population of which it is derived,
      and one should interpret its results with a critical mind.

PMID- 17192908
TI  - Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased
      donor liver transplantation.
AB  - In this retrospective study of hepatitis C virus (HCV)-infected transplant
      recipients in the 9-center Adult to Adult Living Donor Liver Transplantation
      Cohort Study, graft and patient survival and the development of advanced fibrosis
      were compared among 181 living donor liver transplant (LDLT) recipients and 94
      deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and
      patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively.
      Graft survival, but not patient survival, was significantly lower for LDLT
      compared to DDLT (P = 0.04 and P = 0.20, respectively). Further analyses
      demonstrated lower graft and patient survival among the first 20 LDLT cases at
      each center (LDLT <or=20) compared to later cases (LDLT > 20; P = 0.002 and P =
      0.002, respectively) and DDLT recipients (P < 0.001 and P = 0.008, respectively).
      Graft and patient survival in LDLT >20 and DDLT were not significantly different
      (P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT,
      LDLT >20, and LDLT <or=20 were 80%, 79% and 55%, with similar results conditional
      on survival to 90 days (84%, 87% and 68%, respectively). Predictors of graft loss
      beyond 90 days included LDLT <or=20 vs. DDLT (hazard ratio [HR] = 2.1, P = 0.04),
      pretransplant hepatocellular carcinoma (HCC) (HR = 2.21, P = 0.03) and model for
      end-stage liver disease (MELD) at transplantation (HR = 1.24, P = 0.04). In
      conclusion, 3-year graft and patient survival in HCV-infected recipients of DDLT
      and LDLT >20 were not significantly different. Important predictors of graft loss
      in HCV-infected patients were limited LDLT experience, pretransplant HCC, and
      higher MELD at transplantation.

PMID- 17192913
TI  - Prognostic impact of resection margin involvement after extended (D2/D3)
      gastrectomy for advanced gastric cancer: a 15-year experience at a single
      institute.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate whether
      microscopic positive margins are detrimental to the outcome of gastric cancer
      patients treated with extended (D2/3) gastrectomy. METHODS: Among 2,740
      consecutive patients who had undergone extended gastrectomy for advanced gastric
      cancer between January 1987 and December 2002, 49 patients (1.8%) had positive
      resection margins on final histology. RESULTS: Among 49 patients, 29 (59.2%) had
      proximal involved margins and 20 (40.8%) had distal involved margins. The median
      survival time of the positive margin group was 34 months. The negative margin
      group had a significantly longer median survival time of 69 months (P = 0.025).
      When both groups of patients were stratified according to nodal stage, a positive
      resection margin determined a worse prognosis only in patients with node-negative
      disease (174 months vs. 37 months, P = 0.0001). In patients with nodal
      metastasis, the median survival time was similar in both groups. CONCLUSIONS: Our
      results suggest that a positive microscopic margin is associated with a worse
      outcome in patients with node-negative disease. Therefore, a more aggressive
      treatment, such as re-operation, is needed in node-negative patients with a
      positive microscopic disease.

PMID- 17192914
TI  - Proposal for a new definition of true cardia carcinoma.
AB  - BACKGROUND AND OBJECTIVES: It remains controversial whether cardia carcinoma
      should be categorized and treated as esophageal cancer or gastric cancer. The
      purpose of this study was to develop a reasonable definition of cardia carcinoma.
      METHODS: Patients with Siewert type II carcinomas were divided into two
      subgroups: 25 patients with a tumor center within 1 cm of the esophagogastric
      junction (EGJ) (type IIA) and 22 patients with tumor center 1-2 cm aboral of the
      EGJ (type IIB). Patients with subcardia carcinomas, 40 with invasion to the EGJ
      (type III) and 110 without (type IIIe-), were used as controls. RESULTS: The
      patients with type IIB carcinomas showed no different characteristics from those
      with type III or type IIIe- carcinomas, except for the stage of the disease. On
      the other hand, those with type IIA carcinomas were associated with a higher
      male/female ratio, higher incidences of elevated appearance, differentiated
      histology, and mediastinal node metastasis, and a significantly lower survival
      rate as compared with patients with subcardia carcinomas. Multivariate survival
      analysis revealed that type IIA is a significant prognostic determinant, but that
      type IIB is not. CONCLUSION: Type IIA carcinomas should be treated as true cardia
      carcinoma; type IIB as subcardia carcinoma. Our results should be confirmed by a
      prospective study.

PMID- 17192915
TI  - Clear cell sarcoma of soft tissues.
AB  - Clear cell sarcoma (CCS) is a rare but highly malignant tumor of soft tissues
      often appearing as a small tender mass in the deep tissues of the distal
      extremities. We have studied 17 patients with such lesions treated since 1986 and
      have a high incidence of local recurrence and metastasis with a survival rate of
      only 47% despite surgery and for many of the patients, adjuvant therapy. The
      purpose of this article is to warn the readers of the dangers related to treating
      this seemingly benign lesion and urge them to perform wide surgery and utilize
      adjuvant therapy.

PMID- 17192916
TI  - Reaping the harvest from neoadjuvant therapy for breast cancer: reducing
      morbidity with sentinel lymph node biopsy.

PMID- 17192917
TI  - Papillary microcarcinoma of the thyroid.

PMID- 17192918
TI  - Minimal access surgery alters approach to cancer.

PMID- 17192919
TI  - Adjuvant therapy for pancreatic cancer: a time that has not yet come.

PMID- 17192920
TI  - Low molecular weight heparin (LMWH) increases the efficacy of cisplatinum plus
      gemcitabine combination in advanced pancreatic cancer.
AB  - BACKGROUND: In this non-randomized study we aimed to assess the efficacy of the
      addition of low molecular weight heparin (LMWH) to gemcitabine (GEM) plus
      cisplatinum (CDDP) combination chemotherapy on survival by prevention of
      thromboembolic complications in patients with advanced pancreatic cancer (APC).
      PATIENTS AND METHODS: Between November 1999 and February 2004, 69 consecutive
      patients with APC were treated with GEM (800 mg/m2, day 1, day 8) plus CDDP (35
      mg/m2, day 1, day 8) every 21 days +/-LMWH (nadroparine calcium, 2,850 IU/day
      until disease progression). Ten out of 35 patients in LMWH group and 10 out of 34
      patients in chemotherapy alone group had primary inoperable locally advanced
      disease and the rest of the patients had metastatic disease. RESULTS: Total
      response rate was 58.8% (11.7% CR) for the patients treated with LMWH and 12.1%
      for those treated without LMWH (P = 0.0001). LMWH group had a better median time
      to progression (TTP) and survival when compared to control group (7.3 vs. 4.0
      months, P = 0.0001; 13.0 vs. 5.5 months, P = 0.0001). The toxicity was similar
      and acceptable in both groups. CONCLUSION: Addition of LMWH to GEM plus CDDP
      combination significantly improved the response and survival in patients with APC
      and the current schedule deserves to be tested in phase III trials.

PMID- 17192921
TI  - Androgens and androgen receptors: a clinically neglected sector in breast cancer
      biology.

PMID- 17192922
TI  - Excessive superoxide anion generation plays a key role in carcinogenesis.

PMID- 17192923
TI  - Induced and repressed genes after irradiation sensitizing by pentoxyphylline.
AB  - Aim in cancer therapy is to increase the therapeutic ratio eliminating the
      disease while minimizing toxicity to normal tissues. Radiation therapy is a main
      component in targeting cancer. Radiosensitizing agents like pentoxyphylline (PTX)
      have been evaluated to improve radiotherapy. Commonly, cells respond to radiation
      by the activation of specific early and late response genes as well as by
      inhibition of genes, which are expressed under normal conditions. A display of
      the genetic distinctions at the level of transcription is given here to
      characterize the molecular events underlying the radiosensitizing mechanisms. The
      method of suppression subtractive hybridization allows the visualization of both
      induced and repressed genes in irradiated cells compared with cells sensitized
      immediately after irradiation. The genes were isolated by cDNA-cloning,
      differential analysis and sequence similarity search. Genes involved in protein
      synthesis, metabolism, proteolysis and transcriptional regulation were detected.
      It is important that genes like KIAA280, which were only known as unidentified
      EST sequences before without function, but inaccessible by array technology were
      recovered as functional genes. Database searches for PTX-induced genes detected a
      human mRNA completely unknown. In case of suppressed genes, we detected several
      mRNAs; one thereof shows homology to a hypothetical protein possibly involved in
      signal transduction. A further mRNA encodes the protein BM036 supposed to
      associate with the E2F transcription factor. A hypothetical protein H41 was
      detected, which may repress the Her-2/neu receptor influencing breast cancer,
      gliomas and prostate tumors. Radiation combined with PTX may lead to a better
      prognosis by down regulation of the Her-2/neu, which will be proven by clinical
      studies in the near future.

PMID- 17192924
TI  - CNTO 859, a humanized anti-tissue factor monoclonal antibody, is a potent
      inhibitor of breast cancer metastasis and tumor growth in xenograft models.
AB  - Thromboembolic complications are frequently associated with advanced cancer.
      Interestingly, one of the major initiators of blood coagulation, tissue factor
      (TF), is reported to be overexpressed in several tumor types and can be found on
      both tumor cells and tumor vasculature. Although the exact mechanisms have yet to
      be elucidated, TF expressed on tumor cells can trigger intracellular signaling
      events through various pathways that can lead to tumor angiogenesis,
      proliferation, and metastasis. There exists preclinical evidence that disruption
      of TF dependent signaling can effectively inhibit tumor cell migration,
      metastasis, and angiogenesis. Here, we report for the first time that an antibody
      to tissue factor can also prevent tumor growth in vivo. Prophylactic
      administration of CNTO 859, a humanized anti-human TF antibody, was shown to
      inhibit experimental lung metastasis of MDA-MB-231 human breast carcinoma cells
      by over 99% compared to a control antibody. Furthermore, therapeutic doses of
      CNTO 859 were shown to reduce tumor incidence and growth of orthotopically
      implanted MDA-MB-231 cells.

PMID- 17192925
TI  - What should be done to improve the productivity of neurological research?

PMID- 17192926
TI  - Financial anatomy of neuroscience research.
AB  - OBJECTIVE: To estimate the level of funding for neuroscience research from
      federal and industry sources and to examine the therapeutic advances in the
      neurosciences over the past decade. METHODS: We examined financing for
      neuroscience research over the past decade from the following principal sponsors
      of biomedical research: the National Institutes of Health, the pharmaceutical
      industry, large biotechnology firms, and large medical device firms. We also
      examined US Food and Drug Administration approvals for new molecular entities and
      medical devices for indications within the neurosciences. Neuroscience was
      defined to include funding and approvals for neurological and psychiatric
      conditions. RESULTS: Total (nominal) industry and government funding for
      neuroscience research increased from $4.8 billion in 1995 to $14.1 billion in
      2005 and doubled after adjusting for inflation. In 2005, the pharmaceutical
      industry and the largest biotechnology and medical device firms accounted for 58%
      of total funding. The US Food and Drug Administration approved 40 new molecular
      entities for indications within the neurosciences from 1995 to 2005, with the
      annual number of approvals remaining relatively stagnant during this period. From
      1995 to 2005, the US Food and Drug Administration also approved 1,679 medical
      devices in the neurosciences for use. INTERPRETATION: Financing for neuroscience
      research has increased significantly over the past decade, but new approvals for
      drugs in the neurosciences have not kept pace with the rapid increase in funding.
      This lag may represent a natural delay in realizing the return in the investment
      in scientific research or a decline in the productivity of neuroscience research.

PMID- 17192927
TI  - Orally available compound prevents deficits in memory caused by the Alzheimer
      amyloid-beta oligomers.
AB  - OBJECTIVE: Despite progress in defining a pathogenic role for amyloid beta
      protein (Abeta) in Alzheimer's disease, orally bioavailable compounds that
      prevent its effects on hippocampal synaptic plasticity and cognitive function
      have not yet emerged. A particularly attractive therapeutic strategy is to
      selectively neutralize small, soluble Abeta oligomers that have recently been
      shown to mediate synaptic dysfunction. METHODS: Using electrophysiological,
      biochemical, and behavioral assays, we studied how scyllo-inositol (AZD-103;
      molecular weight, 180) neutralizes the acutely toxic effects of Abeta on synaptic
      function and memory recall. RESULTS: Scyllo-inositol, but not its stereoisomer,
      chiro-inositol, dose-dependently rescued long-term potentiation in mouse
      hippocampus from the inhibitory effects of soluble oligomers of cell-derived
      human Abeta. Cerebroventricular injection into rats of the soluble Abeta
      oligomers interfered with learned performance on a complex lever-pressing task,
      but administration of scyllo-inositol via the drinking water fully prevented
      oligomer-induced errors. INTERPRETATION: A small, orally available natural
      product penetrates into the brain in vivo to rescue the memory impairment
      produced by soluble Abeta oligomers through a mechanism that restores hippocampal
      synaptic plasticity.

PMID- 17192929
TI  - Impact of Alzheimer's pathology on cognitive trajectories in nondemented elderly.
AB  - OBJECTIVE: Some individuals who are asymptomatic for dementia while alive have
      substantial Alzheimer's disease (AD) neuropathology at autopsy. We investigated
      whether cognitive trajectories differ between clinically normal elderly
      individuals with and without AD neuropathology and how they compare with
      trajectories of clinically impaired individuals before dementia diagnosis.
      METHODS: Eighty-one elderly participants in the Baltimore Longitudinal Study of
      Aging (BLSA) were followed prospectively with neurological and neuropsychological
      assessments before autopsy evaluation at death. Trajectories of cognitive change
      were estimated for a number of domains using cognitive data before a clinical
      diagnosis of dementia. RESULTS: Clinically normal elderly individuals with and
      without AD-type neuropathology have similar cognitive trajectories across
      different cognitive domains. In contrast, individuals with mild cognitive
      impairment/AD show steeper rates of longitudinal decline in several aspects of
      cognition compared with clinically normal elderly individuals regardless of
      whether the latter have AD neuropathology. Moreover, the cognitive differences
      between impaired and unimpaired groups can be detected years before a diagnosis
      of dementia. INTERPRETATION: Clinically normal individuals with and without AD
      neuropathology do not differ in rates of cognitive decline across a number of
      cognitive domains. Understanding the factors that protect some individuals with
      AD pathology from cognitive impairment may contribute to the maintenance of
      cognitive health in the elderly.

PMID- 17192928
TI  - Cognitive impact of subcortical vascular and Alzheimer's disease pathology.
AB  - OBJECTIVE: To assess the interactions among three types of pathology (ie,
      cerebrovascular disease, hippocampal sclerosis [HS], and Alzheimer's disease
      [AD]), cognitive status, and apolipoprotein E genotype. METHODS: We report
      clinicopathological correlations from 79 autopsy cases derived from a prospective
      longitudinal study of subcortical ischemic vascular disease and AD. RESULTS:
      Thirty percent of the cases had significant cerebrovascular parenchymal pathology
      scores (CVDPS), 54% had significant AD pathology, and 18% had HS. In an ordinal
      logistic regression analysis that included interaction terms to assess the
      effects of each pathological variable when the other variables are interpolated
      to zero, each of the three pathology variables contributed independently to
      cognitive status: Braak and Braak stage odds ratio (OR) = 2.84 (95% confidence
      interval, 1.81-4.45), HS score OR = 2.43 (95% confidence interval, 1.01-5.85),
      and CVDPS OR = 1.02 (95% confidence interval, 1.00-1.04). Only Braak and Braak
      stage contributed to a global neuropsychological measure of cognitive impairment.
      Apolipoprotein E4 genotype was associated with Braak and Braak stage (OR, 1.31
      [95% confidence interval, 1.03-1.68]), but not CVDPS or HS scores.
      INTERPRETATION: In this convenience sample enriched for subcortical ischemic
      vascular disease, HS was a common unsuspected neuropathological finding.
      Apolipoprotein E4 genotype was associated with cerebral amyloid angiopathy, but
      not HS or arteriosclerosis. When Braak and Braak stage was interpolated to zero,
      both CVDPS and HS contributed to cognitive impairment. However, advancing stages
      of AD pathology overwhelmed the effects of CVDPS and HS, to become the major
      determinant of dementia.

PMID- 17192930
TI  - Simvastatin enhances learning and memory independent of amyloid load in mice.
AB  - OBJECTIVE: Normal aging is often associated with a decline in learning and memory
      functions. This decline is manifested to a much greater extent in Alzheimer's
      disease. Recent studies have indicated statins, a class of cholesterol-lowering
      drugs, as a potential therapy for Alzheimer's disease. Our objective was to
      determine whether administering a statin drug (simvastatin) would protect against
      the development of behavioral deficits in an established mouse model of
      Alzheimer's disease. METHODS: Tg2576 mice and their nontransgenic littermates
      were treated with simvastatin and assessed by behavioral tests and biochemical
      analyses. RESULTS: Simvastatin treatment not only reversed learning and memory
      deficits in the Tg2576 mice, but also enhanced learning and memory in the
      nontransgenic mice. Moreover, levels of amyloid beta protein in the brains of
      treated mice did not differ from those of untreated mice. Simvastatin treatment
      was associated with increased expression levels of protein kinase B (Akt) and
      endothelial nitric oxide synthase in the mouse brain. INTERPRETATION: Our
      findings demonstrate that the effects of simvastatin on learning and memory are
      independent of amyloid beta protein levels. The mechanisms by which simvastatin
      exerts its beneficial effects may be related to modulation of signaling pathways
      in memory formation.

PMID- 17192931
TI  - MGMT methylation: a marker of response to temozolomide in low-grade gliomas.
AB  - The methylation status of the O6-methylguanine-methyltransferase promoter (MGMTP)
      was evaluated in 68 low-grade gliomas treated by neoadjuvant temozolomide.
      Methylated MGMTP was detected in 63 of 68 (92.6 %) patients and was a favorable
      predictor of progression-free survival as compared with unmethylated MGMTP tumors
      (p < 0.0001). Assessment of MGMTP status could help identifying low-grade gliomas
      patients more likely to respond to chemotherapy or to benefit from MGMT depletion
      strategies.

PMID- 17192932
TI  - Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides
      structural and functional neuroprotection and neurorestoration in MPTP-treated
      monkeys.
AB  - OBJECTIVE: We tested the hypothesis that gene delivery of the trophic factor
      neurturin could preserve motor function and protect nigrostriatal circuitry in
      hemiparkinsonian monkeys. METHODS: An adeno-associated virus-based vector
      encoding human neurturin (AAV2-NTN; also called CERE-120) was injected into the
      striatum and substantia nigra of monkeys 4 days after a unilateral intracarotid
      injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rendered them
      hemiparkinsonian. Control hemiparkinsonian monkeys received either AAV2 encoding
      green fluorescent protein or formulation buffer. RESULTS: Although stable
      deficits were seen in all control monkeys, AAV2-NTN significantly improved MPTP
      induced motor impairments by 80 to 90% starting at approximately month 4 and
      lasting until the end of the experiment (month 10). AAV2-NTN significantly
      preserved nigral neurons, significantly preserved striatal dopaminergic
      innervation, and activated phospho-extracellular signal-regulated kinase,
      consistent with a mechanism involving a trophic factor-initiated molecular
      cascade. Histological analyses of numerous brain regions, including the
      cerebellum, showed normal cytoarchitecture and no aberrant pathology.
      INTERPRETATION: These data demonstrate that AAV2-NTN (CERE-120) can preserve
      function and anatomy in degenerating nigrostriatal neurons and are supportive of
      ongoing clinical tests in Parkinson's disease patients.

PMID- 17192933
TI  - Correction of humoral derangements from mutant superoxide dismutase 1 spinal
      cord.
AB  - OBJECTIVE: We sought to define molecular and cellular participants that mediate
      motor neuron injury in amyotrophic lateral sclerosis using a coculture system.
      METHODS: We cocultured embryonic stem cell-derived motor neurons with organotypic
      slice cultures from wild-type or SOD1G93A (MT) mice. We examined axon lengths and
      cell survival of embryonic stem cell-derived motor neurons. We defined and
      quantified the humoral factors that differed between wild-type and MT organotypic
      cultures, and then corrected these differences in cell culture. RESULTS: MT
      spinal cord organotypic slices were selectively toxic to motor neurons as defined
      by axonal lengths and cell survival. MT spinal cord organotypic slices secreted
      higher levels of nitric oxide, interleukin (IL)-1beta, IL-6, and IL-12p70 and
      lower levels of vascular endothelial growth factor. The toxicity of MT spinal
      cord organotypic cultures was reduced and axonal lengths were restored to near
      normal by coculturing in the presence of reactive oxygen species scavenger,
      vascular endothelial growth factor, and neutralizing antibodies to IL-1beta, IL
      6, and IL-12. INTERPRETATION: MT spinal cord organotypic cultures overexpress
      certain factors and underexpress others, creating a nonpermissive environment for
      cocultured motor neurons. Correction of these abnormalities as a group, but not
      individually, restores axonal length to near normal. Such a "cocktail" approach
      to the treatment of amyotrophic lateral sclerosis should be investigated further.

PMID- 17192935
TI  - Imaging butyrylcholinesterase activity in Alzheimer's disease.

PMID- 17192936
TI  - Managing transient ischemic attack: Including discussions on end-of-life care.

PMID- 17192939
TI  - A status report on neuroscience research, without grade inflation.

PMID- 17192940
TI  - ER: the gateway for neurologic emergency trials?

PMID- 17192945
TI  - Left ventricular segmental dysfunction following percutaneous transcatheter
      closure of a membranous ventricular septal defect.
AB  - Percutaneous device closure of membranous ventricular septal defects is an
      attractive alternative for surgical treatment. A patient with left ventricular
      segmental dysfunction with infarct like ECG pattern following transcatheter
      membranous VSD closure is presented. Possible pathophysiological mechanisms of
      this phenomenon are discussed.

PMID- 17192944
TI  - Diabetes mellitus does not preclude stabilization or improvement of renal
      function after stent revascularization in patients with kidney insufficiency and
      renal artery stenosis.
AB  - OBJECTIVE: To assess the impact of stent revascularization on the renal function
      of diabetic and nondiabetic patients with renal insufficiency. BACKGROUND: Renal
      artery revascularization has been shown to stabilize or improve renal function in
      patients with significant renal artery stenosis and impaired renal function.
      However, some studies have suggested negligible or no benefit of renal function
      in diabetic patients with the same condition. METHODS: We retrospectively
      compared data from 50 consecutive patients undergoing renal artery stent
      placement with renal insufficiency (serum creatinine > or = 1.5-4.0 mg/dl) and
      global ischemia (bilateral or solitary [single] kidney renal artery stenosis)
      There were 17 diabetic (DM) and 33 nondiabetic (NDM) patients. The endpoints
      included the follow-up measurements of renal function, blood pressure, and number
      of antihypertensive medications. RESULTS: After stent placement, at a mean follow
      up of 42 +/- 18 months (range: 6-62 months), 79% NDM (N = 26), and 76% DM
      patients (N = 13) (P = NS) had improvement in the slope of the reciprocal of
      creatinine (1/SCr), indicating a beneficial effect in renal function in many
      patients. CONCLUSION: Renal artery stent placement appears to be equally
      beneficial in preserving renal function in DM and NDM patients with ischemic
      nephropathy and global renal ischemia.

PMID- 17192946
TI  - Immediate dynamic lymphoscintigraphy delivers no additional value to
      lymphoscintigraphy 3 hr after tracer injection in sentinel lymph node biopsy in
      breast cancer patients.
AB  - OBJECTIVE: Immediate dynamic imaging enables accurate definition of sentinel
      lymph nodes, whereas imaging 3 hr after tracer injection may lead to
      overestimation of the number of sentinel lymph nodes. A study was performed to
      define the value of lymphoscintigraphy immediately versus 3 hr after tracer
      injection in sentinel lymph node biopsy for breast cancer management. METHODS: In
      165 sentinel lymph node biopsy procedures preoperative immediate and 3 hr post
      injection lymphoscintigraphy was performed after intraparenchymal tracer
      administration. RESULTS: Lymph node visualization occurred in 63 immediate
      procedures (38%) versus in 163 procedures 3 hr post-injection (99%). In 17
      procedures (10%) in which immediate lymphoscintigraphy had visualized sentinel
      lymph nodes, additional nodes had been seen on 3 hr post-injection
      lymphoscintigraphy. In eight of these procedures (5%) all nodes were detected in
      the same draining lymph node basin. Non-axillary sentinel lymph nodes were
      identified by preoperative lymphoscintigraphy in 28 procedures (17%) and improved
      staging in three patients (5%). CONCLUSION: The only impact of immediate
      lymphoscintigraphy was the possible omission of removal of 1-2 sec-echelon nodes
      per patient in 5% of patients. We consider this yield too low to continue
      immediate lymphoscintigraphy in breast cancer patients.

PMID- 17192947
TI  - Predictors for long-term survival after interdisciplinary salvage surgery for
      advanced or recurrent gynecologic cancers.
AB  - BACKGROUND AND OBJECTIVES: We wanted to identify factors which allow predicting
      long-term survival after pelvic exenteration (PE) for locally advanced or
      recurrent gynecologic malignancies. METHODS: All patients undergoing PE at our
      institution from 1983 to 2002 were screened. In 203 cases data were obtainable
      and analyzed with respect to factors predicting outcome considering morbidity,
      mortality, and survival. Follow-up data and data concerning late complications
      not documented in our records were obtained by telephone interviews. RESULTS:
      Mean age was 55 (22-77) years. PE was performed for locally advanced (36%) or
      recurrent (64%) cervical (n = 133), endometrial (n = 26), vaginal (n = 23),
      vulvar (n = 10), and ovarian cancer (n = 11, cases with rectum and/or bladder
      resections). In 13.4% (n = 26) the intent of the procedure was palliation in the
      remaining cure. Procedures performed were anterior (n = 91), posterior (45), or
      total (n = 67) PE. 53% of patients underwent preoperative radio-chemotherapy,
      11.8% as a neoadjuvant treatment. Mean OR time was 8.1 hr, an average of 5.6
      units of packed red blood cells were perioperatively transfused. Microscopically
      complete resection was achievable in n = 69 patients. Perioperative mortality was
      1% (n = 2). Seventy-one percent (n = 144) of patients were available for follow
      up. Five-year overall survival in patients treated with a curative intent was
      21%, 5-year survival in those patients with complete resection was 32%. Forty-two
      percent of patients with a complete resection without lymph node involvement, age
      30-50, curative intention, and the absence of a pelvic sidewall infiltration
      survived 5 years or longer. CONCLUSION: In our series a 5-year survival rate of
      over 40% could be achieved for nodal-negative patients without pelvic sidewall
      infiltration when treated with curative intent and after complete resection.

PMID- 17192948
TI  - Should all patients undergoing breast conserving therapy for DCIS receive
      radiation therapy? No. One size does not fit all: an argument against the routine
      use of radiation therapy for all patients with ductal carcinoma in situ of the
      breast who elect breast conservation.

PMID- 17192949
TI  - Comparing aromatase inhibitors in the absence of clinical trial results can be
      misleading.

PMID- 17192950
TI  - Analysis of germline and tumor mutations of p53 gene in familial occurrence of
      soft tissue sarcomas.
AB  - BACKGROUND: Familial soft tissue sarcomas are extremely rare. There is little
      information available on the clinical features and molecular findings of the
      hereditary occurrence of mesenchymal tumor. PATIENTS AND METHODS: A woman and her
      younger brother had malignant fibrous histiocytoma (pleomorphic type) and
      liposarcoma (pleomorphic type) in the lower limbs, respectively. Analysis of p53
      mutations in exons 5-9 of the tumor and in germ-line was done. RESULTS: A guanine
      to adenine substitution occurred in CGC, codon 175 of exon 5 in p53 gene, to CAC
      in the tumor sample of Case 1. Likewise, a thymine to cytosine substitution
      occurred in TTT, codon 270 of exon 8 in p53 gene, to TCT in tumor sample of Case
      2. Germline mutations were not seen in the either patients. CONCLUSIONS:
      Different missense mutations of p53 were detected in each tumor, however no
      germline mutations of p53 were found. The alteration of codon 175 in Case 1 is
      relatively common mutation. On the contrary, the mutation in codon 270 in Case 2
      was extremely rare in cancers. Further molecular investigation is needed to
      understand the mechanism in familial occurrence of sarcomas.

PMID- 17192951
TI  - HTR2C and HTR1A gene variants in German and Italian suicide attempters and
      completers.
AB  - The serotonin 2C (HTR2C) and 1A (HTR1A) receptors have been involved in suicide
      related behaviors. We studied gene variants of both receptors in suicide
      attempters and completers. The sample was composed of 167 German suicide
      attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline
      personality disorder n = 25), 92 Caucasian individuals who committed suicide, 312
      German healthy subjects, 152 Italian suicide attempters (major depression n = 68
      and bipolar disorder n = 84), and 131 Italian healthy volunteers. HTR2C (SNP:
      rs547536, rs2192372, rs6318, rs2428707, rs4272555, rs1801412) and HTR1A (SNP:
      rs1423691, rs878567, and rs6295) variants were analyzed in the German sample.
      HTR2C rs6318 and HTR1A rs6295 were analyzed in the Italian sample. Haplotype
      analysis in relation to suicidal behaviors did not reveal any significant
      association. Single markers and haplotypes were not or only marginally associated
      with other related features, such as violence of suicide attempt, family history
      for suicide attempt or State-Trait Anger Expression Inventory (STAXI) and
      Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion,
      our study does not support the notion that HTR2C and HTR1A gene variants are
      major contributors to suicide-, anger-, or aggression-related behaviors in our
      sample.

PMID- 17192953
TI  - Tumor necrosis factor-alpha promoter polymorphism is associated with the risk of
      Parkinson's disease.
AB  - Inflammatory events may contribute to the pathogenesis of Parkinson's disease
      (PD). We conducted a case-control study in a cohort of 369 PD cases and another
      cohort of 326 ethnically matched controls to investigate the association of tumor
      necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphisms (SNPs)
      with the risk of PD. The overall genotype distribution at T-1031C and C-857T
      sites showed significant difference between PD cases and controls (P = 0.0062 and
      0.0035, respectively). However, only the more frequent -1031 CC genotype was
      evidently associated with PD (P = 0.0085, odds ratio: 2.96; 95% CI: 1.38-7.09).
      Pairwise SNP linkage disequilibrium showed -1031 and -863 sites are in strong
      linkage disequilibrium (D' = 0.93, Delta(2) = 0.80). Pairwise haplotype analysis
      among the four sites showed that -1031C-863A may act as a risk haplotype among PD
      cases (P = 0.0028, odds ratio: 2.18; 95% CI: 1.33-3.69).

PMID- 17192952
TI  - Association study between the TNXB locus and schizophrenia in a Japanese
      population.
AB  - The chromosome 6p21-24 region, which contains the human leukocyte antigen (HLA)
      region, has been suggested as an important locus for a susceptibility gene for
      schizophrenia. Recently, a significant association between schizophrenia and the
      TNXB locus, located immediately telomeric of the NOTCH4 locus in the HLA region,
      was observed. Few studies have further investigated the region in schizophrenia.
      In the present study, we investigated the region in a Japanese population.
      Subjects included 241 patients with schizophrenia and 290 controls. Twenty-six
      single nucleotide polymorphisms (SNPs) and the corresponding haplotypes were
      analyzed. As a result, exactly the same SNPs in the TNXB locus (rs1009382 and
      rs204887) as in the previous study were associated with schizophrenia (P = 0.034
      and 0.034, respectively, uncorrected). A SNP (rs2071287) in the NOTCH4 locus and
      haplotype around it were also suggested to associate with the disease, consistent
      with another previous study (P = 0.041 and permutation P = 0.024, respectively,
      uncorrected). Although these associations became insignificant after Bonferroni
      correction, the findings might provide support for the association of the TNXB
      locus or its adjacent region of the NOTCH4 locus with schizophrenia.

PMID- 17192954
TI  - An investigation of the neurotrophic factor genes GDNF, NGF, and NT3 in
      susceptibility to ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable,
      neurodevelopmental disorder with onset in early childhood. Genes involved in
      neuronal development and growth are, thus, important etiological candidates and
      neurotrophic factors have been hypothesized to play a role in the pathogenesis of
      ADHD. Glial derived neurotrophic factor (GDNF), nerve growth factor (NGF (beta
      subunit)), and neurotrophic factor 3 (NT3) are members of the neurotrophin family
      and are involved in the survival, differentiation, and maintenance of neuronal
      cells. We have examined 10 coding and intronic single nucleotide polymorphisms
      (SNPs) across GDNF, NGF, and NT3 in a family-based association sample of 120 DSM
      IV ADHD probands and their biological parents, as well as a case-control analysis
      with 120 sex-matched controls. Borderline significant overtransmission of the C
      allele of a non-synonymous C/T SNP (rs6330) in NGF which codes an alanine/valine
      change was found in the family-based sample (Chi-square = 3.69, odds ratio (OR) =
      1.65, P = 0.05). Although this SNP is located in the 5' pro-NGF sequence and not
      the mature NGF protein, it may affect intracellular processing and secretion of
      NGF.

PMID- 17192956
TI  - Synaptotagmin XI as a candidate gene for susceptibility to schizophrenia.
AB  - Synaptotagmin XI (Syt11) is a member of the synaptotagmin family, which is
      localized in cells either in synaptic vesicles or the cellular membrane, and is
      known to act as a calcium sensor. The Syt11 gene is located on chromosome locus
      1q21-q22, which was previously reported as a major susceptibility locus of
      familial schizophrenia. Here, we present evidence for an association between the
      number of 33-bp repeats in the promoter region of the Syt11 gene and
      schizophrenia. We found that the transcriptional activity of the gene is affected
      by the number of 33-bp repeats, which include an Sp1 binding site, suggesting
      that the excessive expression of Syt11 can be associated with schizophrenia.
      Another (single nucleotide) polymorphism in the Syt11 5'UTR region, where the
      potent transcription factor YY1 can bind, also affects the transcriptional
      activity of Syt11.

PMID- 17192955
TI  - Association of dopamine transporter genotype with disruptive behavior disorders
      in an eight-year longitudinal study of children and adolescents.
AB  - Associations between dopamine transporter (DAT1) variable number tandem repeats
      (VNTR), genotypes, and disruptive behavior were examined in an 8-year
      longitudinal study of children (n = 183). Half of the children met criteria for
      attention-deficit/hyperactivity disorder (ADHD) at 4-6 years and half were non
      referred comparison children. Consistent with several studies, the non-additive
      association for the 10-repeat allele was significant for hyperactivity
      impulsivity (HI) symptoms. However, consistent with other studies, exploratory
      analyses of the non-additive association of the 9-repeat allele of DAT1 with HI
      and oppositional defiant disorder (ODD) symptoms also were significant. The
      inconsistent association between DAT1 and child behavior problems in this and
      other samples may reflect joint influence of the 10-repeat and 9-repeat alleles.

PMID- 17192957
TI  - The MAOA T941G polymorphism and short-term treatment response to mirtazapine and
      paroxetine in major depression.
AB  - This study investigated the possible association of the MAOA T941G gene variant
      with differential antidepressant response to mirtazapine and/or paroxetine in 102
      patients with major depression (DSM-IV criteria) participating in a randomized
      double-blind controlled clinical trial. Female mirtazapine-treated patients
      homozygous for the T-allele had a significantly faster and better treatment
      response than TG/GG-patients. In males, we failed to show an association between
      MAOA T941G gene variant and mirtazapine response. In the paroxetine-treated
      group, there were no significant differences in treatment response between MAOA
      T941G genotype groups. Time course of response and antidepressant efficacy of
      mirtazapine, but not paroxetine, seem to be influenced in a clinically relevant
      manner by this allelic variation within the MAOA gene, at least in female
      patients. An independent replication of our finding is needed. If replicated,
      genotyping of this locus could become a promising tool to predict response to
      mirtazapine treatment in females suffering from major depression.

PMID- 17192958
TI  - Genomic scan of 12 hereditary prostate cancer families having an occurrence of
      pancreas cancer.
AB  - BACKGROUND: Prostate cancer is a genetically heterogeneous disease. Using the
      occurrence of other cancers in hereditary prostate cancer (HPC) families is a
      promising strategy for developing genetically homogeneous data sets that can
      enhance the ability to identify susceptibility loci using linkage analysis.
      METHODS: Twelve HPC families with the co-occurrence of adenocarcinoma of the
      pancreas were selected from the Prostate Cancer Genetic Research Study
      (PROGRESS). Non-parametric linkage analysis for a prostate/pancreas cancer
      susceptibility phenotype was performed using 441 genome-wide microsatellite
      markers. RESULTS: No statistically significant linkage signal was detected in
      this analysis. The strongest linkage signals, as measured by Kong and Cox LOD
      score (KC LOD), were observed on chromosomes 2q37.2-q37.3 (KC LOD = 1.01; P =
      0.02) and 16q23.2 (KC LOC = 1.05; P = 0.01). CONCLUSIONS: Despite the lack of
      statistically significant findings, four chromosomal regions, three of which (2q,
      16q, 17q) were previously noted as harboring potential susceptibility loci,
      showed suggestive linkage results in this scan.

PMID- 17192959
TI  - Androgen-insensitive prostate cancer cells transiently respond to castration
      treatment when growing in an androgen-dependent prostate environment.
AB  - BACKGROUND: Castration-induced involution of the normal prostate is caused by
      primary effects in the prostate stroma and vasculature, but if this is the case
      also in tumors is unknown. METHODS: Androgen-independent AT-1 prostate tumor
      cells were therefore injected into the ventral prostate (VP) in Copenhagen rats.
      Seven days later when the growing tumor was surrounded by normal VP tissue the
      rats were castrated and the effect examined 3 and 7 days later. RESULTS:
      Castration reduced vascular density in the surrounding VP tissue and this was
      accompanied by tumor cell hypoxia, apoptosis, and temporarily retarded tumor
      growth. Castration-induced VP tissue regression occurred more rapidly in the
      contra-lateral than in the tumor-bearing lobe. CONCLUSIONS: Androgen-independent
      tumor cell respond to castration when growing in an androgen-dependent
      environment. The presence of a tumor influences the castration response in the
      surrounding normal tissue. The microenvironment determines how prostate
      epithelial cells respond to castration.

PMID- 17192960
TI  - Thrombus predicts ischemic complications during percutaneous coronary
      intervention in saphenous vein grafts: results from TARGET (do Tirofiban and
      ReoPro give similar efficacy trial?).
AB  - BACKGROUND: Saphenous vein graft (SVG) percutaneous coronary intervention (PCI)
      carries a high risk of ischemic complications. However, there are scant recent
      data to identify which SVG lesions carry particularly high risk in recent years.
      We studied demographic and angiographic factors associated with ischemic
      complications after SVG PCI without distal protection in the TARGET (do tirofiban
      and reopro give similar efficacy trial?) study. METHODS: TARGET was a multicenter
      double-dummy, double-blinded study randomizing 4,809 PCI patients to tirofiban or
      abciximab. Of these, 254 patients underwent PCI involving an SVG lesion. The
      primary endpoint of this analysis was major adverse cardiac events (MACEs) at 30
      days, including death, nonfatal myocardial infarction (MI), and urgent target
      vessel revascularization. RESULTS: No demographic characteristic was associated
      with 30-day MACE. Lesion length > 20 mm (odds ratio [OR] = 2.7, P = 0.03),
      thrombus (OR = 3.9, P = 0.003), eccentricity (P = 0.001), thrombolysis in
      myocardial infarction flow < 3 post-procedure (OR = 5.6, P = 0.037), and >1
      target lesion (OR = 2.5, P = 0.035) were univariate variables associated with 30
      day MACE. Multivariate analysis associated only thrombus (OR = 3.8, P = 0.015)
      with 30-day MACE. No difference in outcomes was noted between patients receiving
      abciximab and tirofiban. SVG patients had lesser angiographic success (95.6% vs.
      98%, P = 0.04) and increased 30-day Q-wave MI (2.5% vs. 0.9%, P = 0.039) compared
      with non-SVG patients, but a similar incidence of death (0% vs. 0.4%), non-Q-MI
      (5.9% vs. 4.5%), and target vessel revascularization (0.5% vs. 1%). CONCLUSION:
      In the era of routine stenting and GpIIb/IIIa inhibitors, thrombus is the
      angiographic characteristic most closely associated with adverse outcomes of SVG
      PCI.

PMID- 17192962
TI  - Successful use of blunt microdissection catheter in a chronic total occlusion of
      a celiomesenteric artery.
AB  - Chronic mesenteric ischemia is often a disabling condition associated with
      intestinal angina, weight loss, and sitophobia (a morbid aversion of food).
      Significant stenosis of two of the three main arteries of the gut is usually
      required to produce symptoms. Surgical therapy has included reimplantation and
      bypass grafting, usually with synthetic conduits and occasionally endarterectomy.
      Newer techniques have made endovascular treatment an emerging modality in
      managing some of the difficult lesions in the mesenteric circulation that cause
      chronic mesenteric ischemia. We describe the first reported case of blunt
      microdissection using a Frontrunner XP(R) CTO Catheter (Lumend, Redwood City, CA)
      to successfully cross, subsequently wire and stent a four-year-old chronic total
      occlusions in a celiac trunk, which also gave origin to the superior mesenteric
      artery.

PMID- 17192961
TI  - Utility of three-dimensional reconstruction of coronary angiography to guide
      percutaneous coronary intervention.
AB  - OBJECTIVE: The goal of this study was to determine whether three-dimensional (3D)
      reconstruction of traditional coronary angiography could optimize the choice of
      drug-eluting stent (DES) length and number during percutaneous coronary
      intervention (PCI). BACKGROUND: Coronary angiography is subject to significant
      foreshortening artifact that limits the ability of the operator to accurately
      determine lesion length. METHODS: The angiographic images of the target vessels
      of consecutive PCI procedures were postprocessed using a 3D reconstruction
      algorithm. The appropriate length and optimal number of DES to span each target
      lesion were calculated and compared with the number and length of DES actually
      chosen by the operator. RESULTS: A total of 42 target vessels were analyzed, and
      3D reconstruction was successful in 38/42 (90.5%) of cases. The results of 3D
      analysis would have changed operator decision making in six cases (16%): in four
      cases, the stent chosen by the operator was too short requiring an additional
      DES; in two cases, the chosen DES was too long and exchanged for a shorter one.
      In each of these six cases, 3D analysis would have determined the correct stent
      length prior to stent selection. The optimal stent number derived by 3D
      reconstruction was significantly less than the actual number of stents per lesion
      used by the operator (1.31 +/- 0.47 versus 1.54 +/- 0.68, P = 0.01), and the
      optimal stent length trended less than the actual stented length (27.5 +/- 12.8
      mm versus 28.7 +/- 14.7 mm, P = 0.23). CONCLUSIONS: 3D reconstruction algorithm
      of standard coronary angiography is a promising technique to improve DES
      utilization during PCI.

PMID- 17192963
TI  - Preimplantation genetic diagnosis for myotonic dystrophy type 1: detection of
      crossover between the gene and the linked marker APOC2.
AB  - OBJECTIVE: To report two cases of preimplantation genetic diagnosis (PGD) for
      myotonic dystrophy type I (DM1) where cross-over between the DMPK locus and a
      linked polymorphic marker APOC2 was detected. METHODS: Embryos from in vitro
      fertilisation (IVF) were biopsied at day 3 of development and single blastomeres
      collected. Diagnosis was performed by duplex or triplex fluorescent-polymerase
      chain reaction (F-PCR) to amplify DMPK and APOC2 loci, or DMPK with APOC2 and
      D19S112 polymorphic markers. RESULTS: A total of 22 oocytes were retrieved from
      the two patients, 20 were inseminated of which 15 fertilized (75%) and were
      suitable for biopsy on day 3. A diagnosis was obtained for 12 embryos (80%) and
      was confirmed in all un-transferred embryos. Crossover between DM1 and APOC2 was
      detected in two embryos from the two different couples. Transfer of two embryos
      took place in both cases resulting in two pregnancies. Each couple have had a
      healthy baby. CONCLUSION: The above cases highlight the importance of using more
      than one linked polymorphic marker in PGD-PCR protocols and emphasize the danger
      of using APOC2 as the sole marker to identify the DM1 mutation.

PMID- 17192964
TI  - Knowledge of dementia among South Asian (Indian) older people in Manchester, UK.
AB  - OBJECTIVES: The aim of this study was to examine knowledge of dementia in South
      Asian older people, as compared with Caucasian older people. METHODS: Attendees,
      not known to suffer from dementia, of one South Asian and two predominantly
      Caucasian day centres for older people in Manchester (UK) were asked to complete
      the Dementia Knowledge Questionnaire (DKQ). The DKQ was translated into Gujarathi
      and Urdu by the professional translators. RESULTS: One hundred and ninety-one
      DKQs from Indian and 55 DKQs from Caucasian (white UK/Irish/European) older
      people were included in the analyses. Knowledge of dementia was poor in both
      Indian and Caucasian older people, especially so in the former. The median (25th
      75th percentile) total DKQ scores were 3 (2-5) in Indians and 6 (3.5-9) in
      Caucasians (p < 0.001). Indian older people showed significantly less knowledge
      about basic aspects (p < 0.001) and epidemiology (p < 0.001) of dementia when
      compared to Caucasian older people. Both groups faired equally badly on questions
      about aetiology (p = 0.91) and symptomatology (p = 0.66). Indian older people
      were less aware of personality, reasoning, and speech being the affected in
      dementia (p < 0.001, p < 0.001 and p = 0.04, respectively). CONCLUSION: Indian
      older people in Manchester (UK) do not seem to have sufficient knowledge about
      dementia, which may be one of the reasons for their relative absence in the local
      dementia treatment clinics.

PMID- 17192967
TI  - Hairpin-DNA memory using molecular addressing.

PMID- 17192968
TI  - Polyol-mediated synthesis of nanoscale CaF2 and CaF2:Ce,Tb.

PMID- 17192969
TI  - Semisynthetic biogenic magnetosome nanoparticles for the detection of proteins
      and nucleic acids.

PMID- 17192970
TI  - Fabrication of large-scale patterned gold-nanopillar arrays on a silicon
      substrate using imprinted porous alumina templates.

PMID- 17192971
TI  - Spherical bioactive glass with enhanced rates of hydroxyapatite deposition and
      hemostatic activity.

PMID- 17192972
TI  - Continuous tuning of silver nanoparticle size in a water-in-supercritical carbon
      dioxide microemulsion.

PMID- 17192973
TI  - Co-deposition of atomic clusters of different size and composition.

PMID- 17192974
TI  - Dip-pen nanolithography on (bio)reactive monolayer and block-copolymer platforms:
      deposition of lines of single macromolecules.
AB  - The application of atomic force microscopy (AFM) tip-mediated molecular transfer
      (dip-pen nanolithography or DPN) to fabricate nanopatterned (bio)reactive
      platforms based on dendrimers on reactive self-assembled monolayer (SAM) and
      polymer thin films is discussed. The transfer of high-molar-mass polyamidoamine
      (PAMAM) dendrimers (generation 5) and the rapid in situ covalent attachment of
      the deposited adsorbates onto reactive N-hydroxysuccinimide (NHS) terminated SAMs
      on gold and NHS-activated polystyrene-block-poly(tert-butyl acrylate) (PS(690)-b
      PtBA(1210)) block copolymer thin films were investigated as strategies to
      suppress line broadening by surface diffusion in DPN. By exploiting carefully
      controlled environmental conditions (such as temperature and relative humidity),
      scan rates, and in particular the covalent attachment of the dendrimers to the
      reactive films, the observed line broadening and hence the lateral diffusion of
      dendrimers was substantially less pronounced compared to that observed with DPN
      of thiols on gold. By this method, high-definition patterns of dendrimers were
      conveniently fabricated down to 30-nm length scales. The presence of primary
      amino groups in the deposited dendrimers ultimately offers the possibility to
      anchor biochemically relevant molecules, such as proteins and polypeptides, to
      these nanostructured platforms for a wide range of possible applications in the
      life sciences and in particular for the investigation of controlled cell-surface
      interactions.

PMID- 17192975
TI  - Tuning the chemical selectivity of SWNT-FETs for detection of heavy-metal ions.
AB  - A method to functionalize single-walled carbon nanotubes (SWNTs) in a field
      effect transistor (FET) device for the selective detection of heavy-metal ions is
      presented. In this method, peptide-modified polymers were electrochemically
      deposited onto SWNTs and the selective detection of metal ions was demonstrated
      by choosing appropriate peptide sequences. The signal transduction mechanism of
      the peptide-modified SWNT-FETs has also been studied.

PMID- 17192976
TI  - Flowing lattices of bubbles as tunable, self-assembled diffraction gratings.
AB  - We demonstrate tunable, fluidic, two-dimensional diffraction gratings based on a
      microfluidic platform comprising a flow-focusing bubble generator and flowing,
      regular lattices of bubbles formed by dynamic self-assembly. The structure of
      these lattices can be tuned with switching times of less than ten seconds by
      changing the pressures and rates of flow applied to the device. These diffraction
      gratings exhibit high stability (over hours of operation if properly designed and
      operated). For our devices, we achieved tunable ranges in pitch from 12 to 51
      microm, corresponding to first-order diffraction angles from 3.2 degrees to 0.7
      degrees for light with a wavelength of 632 nm.

PMID- 17192977
TI  - Synthesis and characterization of highly ordered cobalt-magnetite nanocable
      arrays.
AB  - Magnetically tunable, high-density arrays of coaxial nanocables within anodic
      aluminum oxide (AAO) membranes have been synthesized. The nanocables consist of
      magnetite nanowires surrounded by cobalt nanotube sheaths and cobalt nanowires
      surrounded by magnetite nanotube sheaths. These materials are a combination of
      separate hard (Co) and soft (Fe3O4) magnetic materials in a single nanocable
      structure. The combination of two or more magnetic materials in such a radial
      structure is seen as a very powerful tool for the future fabrication of
      magnetoresistive, spin-valve and ultrafast spin-injection devices with nonplanar
      geometries. The nanocable arrays were prepared using a supercritical-fluid
      inclusion process, whereby the nanotube was first deposited onto the pore walls
      of the nanoporous membranes and subsequently filled with core material to form
      coaxial nanocables. In essence, this paper describes a technique for placing
      novel magnetic technologies into well-defined building blocks that may ultimately
      lead to new multifunctional devices, such as spin valves and high-density
      magnetic storage devices.

PMID- 17192978
TI  - The empirical correlation between size and two-photon absorption cross section of
      CdSe and CdTe quantum dots.
AB  - The tuning of CdSe quantum dot (QDs) sizes, and consequently their corresponding
      two-photon absorption (TPA) cross section, has been systematically investigated.
      As the size (diameter) of the quantum dots increases, the TPA cross section is
      found to be empirically related via a power-law proportionality of 3.5+/-0.5 and
      5.6+/-0.7 to the diameters of CdSe and CdTe QDs, respectively. The results are
      tentatively rationalized via a theoretical model of two-photon excitation
      properties in a system incorporating excitons and defects.

PMID- 17192979
TI  - Formation of CdS nanoparticle necklaces with functionalized dendronized polymers.
AB  - A one-dimensional assembly of cadmium sulfide (CdS) nanoparticles was prepared by
      using functionalized polymers with pendant Frechet-type dendritic wedges of
      different generation. The novel dendronized polymers acted as both nanoreactors
      for the formation of CdS nanoparticles and a template to arrange the
      nanoparticles into a necklace. The polymers of different dendron generation were
      applied to stabilize CdS particles and the effect of dendron size was observed.
      CdS nanoparticle necklaces were obtained successfully when polymers bearing
      second-generation dendrons were applied.

PMID- 17192981
TI  - Using biological inspiration to engineer functional nanostructured materials.
AB  - Humans have always looked to nature for design inspiration, and material design
      on the molecular level is no different. Here we explore how this idea applies to
      nanoscale biomimicry, specifically examining both recent advances and our own
      work on engineering lipid and polymer membrane systems with cellular processes.

PMID- 17192982
TI  - Printed arrays of aligned GaAs wires for flexible transistors, diodes, and
      circuits on plastic substrates.

PMID- 17192983
TI  - Photoinduced phase separation of gold in two-component nanoparticles.

PMID- 17192984
TI  - Surfactant-directed assembly of [corrected] Pt nanoparticles into colloidal
      spheres and their use [corrected] as substrates in forming Pt nanorods and
      nanowires.

PMID- 17192985
TI  - SiC-shell nanostructures fabricated by replicating ZnO nano-objects: a technique
      for producing hollow nanostructures of desired shape.

PMID- 17192986
TI  - Molecular-dynamic studies of carbon-water-carbon composite nanotubes.
AB  - We recently reported the discovery via molecular-dynamic simulations that single
      walled carbon nanotubes (SWCNTs) with different diameters, lengths, and
      chiralities can coaxially self-assemble into multi-walled carbon nanotubes
      (MWCNTs) in water via the spontaneous insertion of smaller tubes into larger
      ones. Here, we extend that study to investigate the various water structures
      formed between two selected SWCNTs after such coaxial assembly. Depending on the
      tube geometry, typical water structures, besides the bulk phase, include a one
      dimensional (1D) ordered water chain inside the smaller tube, a uniform or
      nonuniform water shell between the two tubes, and a "boundary layer" of water
      near the exterior wall of the larger tube. It was found that a concentric water
      shell consisting of up to three layers of water molecules can form between the
      two SWCNTs, which leads to a class of carbon-water-carbon composite nanotubes.
      Analysis of the potential energy of the SWCNT-water system indicated that the
      composite nanotubes are stabilized by both the tube-tube and tube-water van der
      Waals interactions. Geometrically confined between the two SWCNTs, water mono-
      and bilayers are found to be stable, highly condensed, and ordered, although the
      average number of hydrogen bonds per water molecule is reduced. In contrast, a
      water trilayer between the two CNTs can be easily disrupted by thermal
      fluctuations.

PMID- 17192987
TI  - Carbon nanotube-DNA nanoarchitectures and electronic functionality.
AB  - Biological molecules such as deoxyribonucleic acid (DNA) possess inherent
      recognition and self-assembly capabilities, and are attractive templates for
      constructing functional hierarchical material structures as building blocks for
      nanoelectronics. Here we report the assembly and electronic functionality of
      nanoarchitectures based on conjugates of single-walled carbon nanotubes (SWNTs)
      functionalized with carboxylic groups and single-stranded DNA (ssDNA) sequences
      possessing terminal amino groups on both ends, hybridized together through amide
      linkages by adopting a straightforward synthetic route. Morphological and
      chemical-functional characterization of the nanoarchitectures are investigated
      using scanning electron microscopy, transmission electron microscopy, atomic
      force microscopy, energy-dispersive X-ray spectroscopy, Raman spectroscopy, and
      Fourier-transform infrared spectroscopy. Electrical measurements (I-V
      characterization) of the nanoarchitectures demonstrate negative differential
      resistance in the presence of SWNT/ssDNA interfaces, which indicates a biomimetic
      route to fabricating resonant tunneling diodes. I-V characterization on platinum
      metallized SWNT-ssDNA nanoarchitectures via salt reduction indicates modulation
      of their electrical properties, with effects ranging from those of a resonant
      tunneling diode to a resistor, depending on the amount of metallization. Electron
      transport through the nanoarchitectures has been analyzed by density functional
      theory calculations. Our studies illustrate the great promise of biomimetic
      assembly of functional nanosystems based on biotemplated materials and present
      new avenues toward exciting future opportunities in nanoelectronics and
      nanobiotechnology.

PMID- 17192988
TI  - Ordered assembly of alpha-quinquethiophene on a copper oxide nanotemplate.
AB  - The organic semiconductor alpha-quinquethiophene (T5) is used as the active layer
      in organic field-effect transistors. We have investigated the adsorption of T5 on
      the (110) surface of copper and on the CuO nanotemplate formed by the high
      temperature exposure of Cu(110) to molecular oxygen. The results were obtained
      with high-resolution scanning tunneling microscopy (STM) under ultra-high-vacuum
      (UHV) conditions. The adsorption of T5 on copper is an important model system
      because it mimics the active-layer-electrode interface in organic devices. The
      molecules were observed to adsorb onto both the pristine Cu(110) surface and the
      CuO nanotemplate, showing a greater affinity for the pristine copper surface.
      Surprisingly, however, the T5 molecules assembled with a much higher degree of
      long-range order on the oxygen-passivated portion of the surface.

PMID- 17192990
TI  - Sequential reactions with amine-terminated monolayers and isolated molecules on
      H/Si(111).
AB  - A simple method for preparing monolayers with terminal amine functionality is
      demonstrated. A gas-phase photochemical reaction of 1,3-diaminopropane with a H
      terminated Si(111) surface results in the molecules covalently attaching to the
      surface, primarily through the formation of a Si--N bond. These monolayers are
      characterized by scanning tunneling microscopy (STM) and high-resolution electron
      energy loss spectroscopy (HREELS). The reactivity of the terminal amine is
      confirmed by exposing the monolayer to benzaldehyde, resulting in the formation
      of an imine link and the grafting of phenyl rings onto the surface. For short
      irradiation times, this reaction leads to the formation of isolated amine groups
      on an otherwise pristine H-terminated surface. STM and HREELS studies of the
      benzaldehyde reaction on these low-coverage surfaces (less than 0.005 monolayers)
      indicate that the reaction is restricted to the reactive amine groups, leaving
      the remainder of the surface unaffected. This simple approach for a sequential
      coupling reaction is expected to facilitate attachment of more complex molecules
      (molecular switches, biomolecules) for single-molecule STM studies.

PMID- 17192989
TI  - Materials specificity and directed assembly of a gold-binding peptide.
AB  - Adsorption studies of a genetically engineered gold-binding peptide, GBP1, were
      carried out using a quartz-crystal microbalance (QCM) to quantify its molecular
      affinity to noble metals. The peptide showed higher adsorption onto and lower
      desorption from a gold surface compared to a platinum substrate. The material
      specificity, that is, the preferential adsorption, of GBP1 was also demonstrated
      using gold and platinum micropatterned on a silicon wafer containing native
      oxide. The biotinylated three-repeat units of GBP1 were preferentially adsorbed
      onto gold regions delineated using streptavidin-conjugated quantum dots (SAQDs).
      These experiments not only demonstrate that an inorganic-binding peptide could
      preferentially adsorb onto a metal (Au) rather than an oxide (SiO2) but also onto
      one noble metal (Au) over another (Pt). This result shows the utility of an
      engineered peptide as a molecular erector in the directed immobilization of a
      nanoscale hybrid entity (SAQDs) over selected regions (Au) on a fairly complex
      substrate (Au and Pt micropatterned regions on silica). The selective and
      controlled adsorption of inorganic-binding peptides may have significant
      implications in nano- and nanobiotechnology, where they could be genetically
      tailored for specific use in the development of self-assembled molecular systems.

PMID- 17192995
TI  - Medical application of carbon-nanotube-filled nanocomposites: the microcatheter.
AB  - Carbon nanotubes hold great promise for use in biomedical fields. Among numerous
      potential applications, including DNA and protein sensors, bioseparators,
      biocatalysts, and tissue scaffolds, this article emphasizes the use of carbon
      nanotube-filled polymer composites as medical devices, namely, microcatheters.
      The currently hot topic of the biocompatibility (e.g., toxic properties) of
      carbon nanotubes is discussed. In addition, critical issues that must be
      clarified for the full utilization of current carbon-nanotube science and
      technology in biomedical fields are discussed.

PMID- 17192997
TI  - One-dimensional self-assembly of metallic nanostructures on single-walled carbon
      nanotube bundles.

PMID- 17192996
TI  - Evaluation of quantum dot cytotoxicity based on intracellular uptake.

PMID- 17192998
TI  - Room-temperature single-electron tunneling in dendrimer-stabilized gold
      nanoparticles anchored at a molecular printboard.

PMID- 17192999
TI  - Direct observation of ferroelectricity in quasi-zero-dimensional barium titanate
      nanoparticles.

PMID- 17193000
TI  - X-ray spectromicroscopy of polymer/fullerene composites: quantitative chemical
      mapping.

PMID- 17193001
TI  - V-shaped tin oxide nanostructures featuring a broad photocurrent signal: an
      effective visible-light-driven photocatalyst.

PMID- 17193002
TI  - Cicada wings: a stamp from nature for nanoimprint lithography.

PMID- 17193003
TI  - Deposition of nanobead hexagonal crystals using silicon microcantilevers.

PMID- 17193004
TI  - Assembly and alignment of metallic nanorods on surfaces with patterned
      wettability.

PMID- 17193005
TI  - Design and synthesis of colloidal nanocrystal heterostructures with tetrapod
      morphology.

PMID- 17193006
TI  - Impedance characterization of ZnO nanobelt/Pd Schottky contacts in ammonia.

PMID- 17193007
TI  - Rapid deposition and long-range alignment of nanocoatings and arrays of
      electrically conductive wires from tobacco mosaic virus.

PMID- 17193008
TI  - Stretching and breaking of a molecular junction.
AB  - Density functional theory (DFT) calculations based on band structure are used to
      investigate the electromechanical properties of a molecular junction consisting
      of a dithiolbenzene molecule sandwiched between two gold slabs. This represents a
      prototypical system for the field of molecular electronics; such a system has
      previously been studied in break-junction measurements and electron-transport
      calculations. The stretching and breaking behavior of the junction is analyzed
      for different geometric conformations, and it is found that the breakage occurs
      through dissociation of one of the sulfur-gold bonds with a maximum force of 1.25
      nN. The molecular electronic states shift during stretching, and, at the point of
      highest stress in the junction, the highest occupied molecular orbital (HOMO) of
      the molecule is located exactly at the Fermi level.

PMID- 17193009
TI  - Core-shell iron-iron oxide nanoparticles synthesized by laser-induced pyrolysis.
AB  - Passivated iron nanoparticles (10-30 nm) have been synthesized by laser pyrolysis
      of a mixture of iron pentacarbonyl and ethylene vapors followed by controlled
      oxidation. The nanoparticles show a well-constructed iron-iron oxide core-shell
      structure, in which the thickness and nature (structure similar to maghemite,
      gamma-Fe2O3) of the shell is found to be independent of the initial conditions.
      On the other hand, the composition of the core is found to change with the
      particle size from the alpha-Fe structure to a highly disordered Fe phase
      (probably containing C atoms in its structure). The dependence of the magnetic
      properties on the particle size, iron oxide fraction, and temperature was also
      investigated. In the case of smaller particles, the magnetic data indicate the
      existence at low temperature of a large exchange anisotropy field, the magnitude
      of which increases with decreasing temperature in correspondence with the
      freezing of magnetic moments in the oxide shell.

PMID- 17193010
TI  - In situ electron microscopy electromechanical characterization of a bistable NEMS
      device.
AB  - A previously proposed two-terminal carbon-nanotube-based device with closed-loop
      feedback is demonstrated through in situ scanning electron microscopy (SEM)
      experiments. The pull-in/pull-out tests were carried out using a multi-walled
      carbon nanotube (MWCNT) welded to a conductive probe attached to a
      nanomanipulator. The MWCNTs were cantilevered over a gold electrode and
      electrostatically actuated. The measured current-voltage curves exhibited the
      theoretically predicted hysteretic loop between the pull-in and pull-out
      processes. Both experiments and theoretical modeling demonstrated the bistability
      of the device confirming its utility in applications such as memory elements,
      NEMS switches, and logic devices. Failure mechanisms observed during the pull
      in/pull-out event are also reported and discussed.

PMID- 17193011
TI  - Growing one-dimensional metallic nanowires by dielectrophoresis.
AB  - We report an electrical-field-controlled growth process for the directed bottom
      up assembly of one-dimensional palladium nanowires between microfabricated
      electrodes. The wires, grown from an aqueous palladium salt solution by
      dielectrophoresis, have a thickness of only 5-10 nm and a length of up to several
      micrometers. The growth process depends largely on both the strength of the
      applied ac field and the concentration of the metal salt solution. The conditions
      for optimum growth are evaluated. Room-temperature current-voltage measurements
      show ohmic behavior and indicate electromigration effects at higher voltages. Low
      temperature transport measurements reveal localization effects with a
      characteristic resistance minimum at 20 K. The temperature dependence below the
      minimum shows the wires to be one dimensional in their electron-transport
      properties. The investigated growth method is capable of building complex circuit
      patterns for future nanoelectronics.

PMID- 17193012
TI  - Structural relaxation in charged metal surfaces and cluster ions.
AB  - Space-charge layers can noticeably affect the properties of metal electrode
      surfaces, for instance by modifying the surface dielectric response or indirectly
      via the induced atomic relaxations. While there are efforts to exploit this
      concept for designing novel functional nanomaterials, the underlying microscopic
      processes are poorly understood. Here, we report on a density functional theory
      (DFT) study of atomic relaxation in Au cluster ions comprising up to 309 atoms.
      Suitable averages over atomic displacements respond to charging consistent with
      experimental observation on macroscopic Au single-crystal surfaces. Moreover, the
      overall DFT response is also consistent with predictions of a simple
      phenomenological model. Motivated by our observations, we propose a scenario in
      which the surface relaxation ("stretch") results from out-of-plane Hellman
      Feynman forces exerted on the surface atoms by the excess charge, and where the
      in-plane surface stress represents essentially an elastic transverse contraction
      tendency of the surface layer in response to stretch.

PMID- 17193013
TI  - Pore conductivity control at the hundred-nanometer scale: an experimental and
      theoretical study.
AB  - We report on the observation of an unexpected mechanism that controls
      conductivity at the 100-nm scale on track-etched polycarbonate membranes.
      Transport measurements of positively charged methyl viologen performed by
      absorption spectroscopy under various pH conditions demonstrate that for 100-nm
      diameter pores at pH 2 conductivity is blocked, while at pH 5 the ions move
      through the membrane according to diffusion laws. An oppositely charged molecular
      ion, naphthalene disulfonate, in the same membrane, shows the opposite trend:
      diffusion of the negative ion at pH 2 and very low conductivity at pH 5. The
      influence of parameters such as ionic strength and membrane surface coating are
      also investigated. A theoretical study of the system shows that at the 100-nm
      scale the magnitude of the electric field in the vicinity of the pores is too
      small to account for the experimental observations; rather, it is the surface
      trapping of the mobile ion (Cl- or Na+) that gives rise to the observed control
      of the conductivity. This surprising effect has potential applications for high
      throughput separation of large molecules and bio-organisms.

PMID- 17193017
TI  - Molecular signatures in the transport properties of molecular wire junctions:
      what makes a junction "molecular"?
AB  - The simplest component of molecular electronics consists of a single-molecule
      transport junction: a molecule sandwiched between source and drain electrodes,
      with or without a third gate electrode. In this Concept article, we focus on how
      molecules control transport in metal-electrode molecular junctions, and where the
      molecular signatures are to be found. In the situation where the molecule is
      relatively short and the gap between injection energy and molecular eigenstates
      is large, transport occurs largely by elastic tunneling, stochastic switching is
      common, and the vibronic signature can be found using inelastic electron
      tunneling spectroscopy (IETS). As the energy gaps for injection become smaller,
      one begins to see stronger molecular signatures - these include Franck-Condon
      like structures in the current/voltage characteristic and strong vibronic
      interactions, which can lead to hopping behavior at the polaron limit.
      Conformational changes induced by the strong electric field lead to another
      strong manifestation of the molecular nature of the junction. We overview some of
      this mechanistic landscape, focusing on significant effects of switching (both
      stochastic and controlled by the electric field) and of molecular vibronic
      coupling.

PMID- 17193018
TI  - Metal nanoparticles and related materials supported on carbon nanotubes: methods
      and applications.
AB  - Carbon nanotubes are one of the most intensively explored nanostructured
      materials. In particular, carbon nanotubes are unique and ideal templates onto
      which to immobilize nanoparticles allowing the construction of designed
      nanoarchitectures that are extremely attractive as supports for heterogeneous
      catalysts, for use in fuel cells, and in related technologies that exploit the
      inherent 'smallness' and hollow characteristics of the nanoparticles. Here we
      overview the recent developments in this area by exploring the various techniques
      in which nanotubes can be functionalized with metals and other nanoparticles and
      explore the diverse applications of the resulting materials.

PMID- 17193019
TI  - Conical nanopore membranes: controlling the nanopore shape.

PMID- 17193020
TI  - Tunable 3D arrays of quantum dots: synthesis and luminescence properties.

PMID- 17193021
TI  - Blinking and surface chemistry of single CdSe nanocrystals.

PMID- 17193023
TI  - Electrohydrodynamic jet processing: an advanced electric-field-driven jetting
      phenomenon for processing living cells.

PMID- 17193022
TI  - Specific targeting, cell sorting, and bioimaging with smart magnetic silica core
      shell nanomaterials.

PMID- 17193024
TI  - Nanoengineered polymeric thin films by sintering CNT-coated polystyrene spheres.

PMID- 17193025
TI  - Reflow and electrical characteristics of nanoscale solder.

PMID- 17193026
TI  - Surface-charge-induced reversible phase transitions of Bi nanoparticles.

PMID- 17193027
TI  - Ferromagnetic FePt nanowires: solvothermal reduction synthesis and
      characterization.

PMID- 17193028
TI  - Size effects on the stiffness of silica nanowires.

PMID- 17193029
TI  - Synthesis and size-dependent magnetic properties of monodisperse EuS
      nanocrystals.

PMID- 17193030
TI  - Synthesis of porous platinum nanoparticles.

PMID- 17193031
TI  - Ordered mesoporous silica SBA-15: a new effective adjuvant to induce antibody
      response.

PMID- 17193033
TI  - Making electrical nanocontacts to nanocrystal assemblies: mapping of room
      temperature Coulomb-blockade thresholds in arrays of 28-kDa gold nanocrystals.

PMID- 17193032
TI  - Mn-doped silicate micro/nanowire bundles on silicon wafers: synthesis and visible
      luminescence.

PMID- 17193034
TI  - Nanostructures of Sn and their enhanced, shape-dependent superconducting
      properties.
AB  - A noncatalytic and template-free vapor transport process was developed to make
      possible simultaneous growth of single-crystalline tin nanowires, nanosquares,
      nanodisks, and polycrystalline nanoparticles. The formation of such a rich
      variety of morphologies in a single growth experiment can be attributed to
      variations in the growth rate among different crystallographic planes when
      employing the vapor-solid growth mechanism. Structural characterization with high
      resolution transmission electron microscopy reveals a preferential growth
      direction of [100] in Sn nanowires, nanosquares, and nanodisks. Shape-dependent
      superconducting properties are observed. These four types of Sn nanostructures
      all show typical diamagnetic behavior in magnetization measurements, with the
      three anisotropically shaped nanostructures (nanowires, nanosquares, and
      nanodisks) showing one order of magnitude enhancement in the working magnetic
      field ranges for superconductivity, compared to bulk Sn and Sn nanoparticles. The
      magnetic field range is broadest for nanowires, followed by nanodisks,
      nanosquares, and nanoparticles.

PMID- 17193035
TI  - Directed fabrication of radially stacked multifunctional oxide heterostructures
      using soft electron-beam lithography.
AB  - A versatile patterning approach based on electron-beam lithography (eBL) and
      solution deposition, termed soft-eBL, has been developed to fabricate radially
      stacked heterostructures of multifunctional oxides from their sol precursors.
      Well-defined nanorings of lead zirconate titanate (PZT) are fabricated on a
      variety of substrates such as noble metals (e.g., Au), semiconductors (e.g., Si),
      and oxide single crystals (e.g., SrTiO3), which were previously functionalized
      with appropriate self-assembled monolayers (SAMs). The undercut in the double
      layer eBL resist and substrate functionalization with the SAM treatment play a
      vital role in the formation of the ring structures. The nanorings are then used
      as building block "containers" and ring-reservoirs are filled with a second sol
      (e.g., CoFe2O4) to form radially stacked composite ceramic heterostructures. The
      approach presented here does not require either feature alignment to realize
      heterostructures or the etching of ceramics, and is amenable to a variety of
      radially stacked composite heterostructures.

PMID- 17193036
TI  - Efficient designs for powering microscale devices with nanoscale biomolecular
      motors.
AB  - Current MEMS and microfluidic designs require external power sources and
      actuators, which principally limit such technology. To overcome these
      limitations, we have developed a number of microfluidic systems into which we can
      seamlessly integrate a biomolecular motor, kinesin, that transports microtubules
      by extracting chemical energy from its aqueous working environment. Here we
      establish that our microfabricated structures, the self-assembly of the bio
      derived transducer, and guided, unidirectional transport of microtubules are
      ideally suited to create engineered arrays for efficiently powering nano- and
      microscale devices.

PMID- 17193041
TI  - Towards rapid DNA sequencing: detecting single-stranded DNA with a solid-state
      nanopore.

PMID- 17193042
TI  - Nanoscale biosensors: significant advantages over larger devices?

PMID- 17193043
TI  - Shape control of II-VI semiconductor nanomaterials.
AB  - Anisotropic II-VI semiconductor nanocrystals and nanoparticles have become
      important building blocks for (potential) nanotechnological applications. Even
      though a wide variety of differently shaped nanoparticles of this class can be
      prepared, the underlying mechanisms are mostly not fully understood. This Review
      article provides a brief overview of the currently studied shape-evolution
      mechanisms and the most prominent synthesis methods for such particles, with an
      aim to provide a fundamental understanding on how different morphologies evolve,
      and to function as a tool to aid in the preparation of specific nanocrystals.

PMID- 17193044
TI  - Selective loading of kinesin-powered molecular shuttles with protein cargo and
      its application to biosensing.

PMID- 17193045
TI  - Rapid detection of Escherichia coli by using antibody-conjugated silver
      nanoshells.
AB  - Silver shells of 20 nm thickness have been deposited on silica particles of 200
      nm diameter with narrow size distribution. Silver nanoshells dispersed in water
      exhibit a strong surface plasmon resonance band at 443 nm. This band was found to
      be very sensitive to rabbit immunoglobulin G antibodies, which were anchored on
      the nanoshells. These in turn could be utilized to detect the presence of small
      (approximately 5) to large numbers (approximately 10(9)) of Escherichia coli in
      water. The protocol presented here proves to be a specific, rapid, reliable, and
      inexpensive method to detect E. coli.

PMID- 17193046
TI  - Chemically modified multiwalled carbon nanotubes as an additive for
      supercapacitors.

PMID- 17193047
TI  - Efficient anchoring of silver nanoparticles on N-doped carbon nanotubes.

PMID- 17193048
TI  - The completion of the platonic atomic polyhedra: the dodecahedron.

PMID- 17193049
TI  - Investigation of a single Pd nanowire for use as a hydrogen sensor.

PMID- 17193050
TI  - Effect of the orientation of CdSe nanorods on the electron mobility of CdSe/P4VP
      nanodomains self-assembled within a poly(styrene-b-4-vinylpyridine) diblock
      copolymer thin film.

PMID- 17193051
TI  - Self-assembled cylindrical lipid tubules with a birefringent core.

PMID- 17193052
TI  - Tetrahedral zinc blende tin sulfide nano- and microcrystals.

PMID- 17193053
TI  - Hybrid permeable-base transistors based on an indenofluorene derivative.

PMID- 17193054
TI  - Glass-bead-based parallel detection of DNA using composite Raman labels.

PMID- 17193055
TI  - Active capture and transport of virus particles using a biomolecular motor
      driven, nanoscale antibody sandwich assay.

PMID- 17193056
TI  - Atomistic insights for InAs quantum dot formation on GaAs(001) using STM within a
      MBE growth chamber.

PMID- 17193057
TI  - Bottom-up synthesis of titanate nanosheets with hierarchical structures and a
      high specific surface area.

PMID- 17193058
TI  - Combined atomic force microscopy and optical microscopy measurements as a method
      to investigate particle uptake by cells.
AB  - We propose a combination of atomic force microscopy (AFM) and optical microscopy
      for the investigation of particle uptake by cells. Positively and negatively
      charged polymer microcapsules were chosen as model particles, because their
      interaction with cells had already been investigated in detail. AFM measurements
      allowed the recording of adhesion forces on a single-molecule level. Due to the
      micrometer size of the capsules, the number of ingested capsules could be counted
      by optical microscopy. The combination of both methods allowed combined
      measurement of the adhesion forces and the uptake rate for the same model
      particle. As a demonstration of this system, the correlation between the adhesion
      of positively or negatively charged polymer microcapsules onto cell surfaces and
      the uptake of these microcapsules by cells has been investigated for several cell
      lines. As is to be expected, we find a correlation between both processes, which
      is in agreement with adsorption-dependent uptake of the polymer microcapsules by
      cells.

PMID- 17193059
TI  - Chemical mapping of individual semiconductor nanostructures.
AB  - We demonstrate experimentally the power of a novel analytical tool for X-ray
      spectromicroscopy. This provides a minimally intrusive elemental mapping of
      surfaces at the nanoscale and holds the promise of remarkable versatility. We
      have applied our procedure to the characterization of Ge(Si) islands on Si(111)
      substrates, with the aim of investigating the surface stoichiometry gradients and
      gaining insight into the intermixing dynamics. By identifying Si-richer edges
      with respect to the centers, we are able to associate alloying in these islands
      to surface transport processes.

PMID- 17193060
TI  - pH-sensitive dispersion and debundling of single-walled carbon nanotubes:
      lysozyme as a tool.
AB  - Highly dispersed and debundled carbon nanotubes were prepared in an aqueous
      solution of lysozyme using a combination of ultrasonication and
      ultracentrifugation. The product is a pH-sensitive dispersion, which remains in a
      highly dispersed state at pH<8 and pH>11, but in an aggregated state at pH 8-11.
      Photoluminescence measurements show that by changing the pH value, a reversible
      conversion of the highly dispersed state to the aggregated state (or vice versa)
      could be observed. Circular dichromism analysis confirmed that the secondary
      structure, as well as the majority of the tertiary structure, remains intact.
      Some lysozyme molecules were irreversibly bound to the nanotubes, which is
      possibly due to pi-pi or hydrophobic interactions. However, these interactions
      alone are not enough to produce fine dispersions of the nanotubes. Protonated
      amine interactions on the defect sites of the nanotubes play a vital role in the
      stabilization of the nanotubes below the isoelectric point and amine adsorption
      on the sidewalls of nanotubes occurs in cases where the pH value is higher than
      the isoelectric point.

PMID- 17193061
TI  - Synthesis of TiO2-Au composites by titania-nanorod-assisted generation of gold
      nanoparticles at aqueous/nonpolar interfaces.
AB  - Hydrophobically coated anatase TiO(2) nanorods can assist the reduction of
      AuCl(4) (-)ions at aqueous/nonpolar solvent interfaces, which results in the
      generation of organic-soluble Au nanoparticles with tunable size in the absence
      of any metal ligands and/or phase-transfer agents. The titania-nanorod-driven
      modulation of interfacial energy and catalysis of gold nucleation provide
      straightforward access to nanocomposite solutions of TiO(2)-stabilized Au
      nanoparticles. Among colloidal approaches, this method represents a unique tool
      for the surfactantless, large-scale preparation of nanostructured semiconductor
      metal hybrid systems with relevant technological potential in catalysis,
      photocatalysis, and charge-storage processes.

PMID- 17193062
TI  - Growth and characterization of iron oxide nanorods/nanobelts prepared by a simple
      iron-water reaction.
AB  - Single-crystalline hexagonal alpha-Fe(2)O(3) nanorods/nanobelts have been created
      by a simple iron-water reaction in the low-temperature range of 350-450 degrees
      C. Scanning electron microscopy examination shows that the needle-like products,
      radiating from and perpendicular to the original large iron particle surfaces,
      are up to a few micrometers in length with an average diameter from 20 nm (tip)
      to 100 nm (base). X-ray photoelectron spectroscopy and FTIR spectroscopy reveal
      that the outermost surface of the nanorods consists of Fe(2)O(3) without organic
      impurity contaminants, which could possibly result from other methods, such as
      hydrothermal growth. Nanobelt-like structures are believed to result from a
      combination of increased reaction temperature and time. The initial formation and
      subsequent growth of alpha-Fe(2)O(3) nanorods may be explained by the iron metal
      corrosion mechanism.

PMID- 17193066
TI  - 1st International Workshop on "Electrical Functionality in Nanoarchitectures".

PMID- 17193067
TI  - Nanoscopic medicine: the next frontier.
AB  - The extraordinary progress that has taken place in cell science and optical
      nanoscale microscopy has led recently to the concept of medical nanoscopy. Here,
      we lay out a concept for developing live cell nanoscopy into a comprehensive
      diagnostic and therapeutic scheme referred to as nanoscopic medicine, which
      integrates live cell nanoscopy with the structural and functional studies of
      nanoscopic protein machines (NPMs), the systems biology of NPMs, fluorescent
      labeling, nanoscopic analysis, and nanoscopic intervention, in order to advance
      the medical frontier toward the nanoscopic fundament of the cell. It aims at the
      diagnosis and therapy of diseases by directly visualizing, analyzing, and
      modifying NPMs and their networks in living cells and tissues.

PMID- 17193068
TI  - Nanomachining by colloidal lithography.
AB  - Colloidal lithography is a recently emerging field; the evolution of this simple
      technique is still in progress. Recent advances in this area have developed a
      variety of practical routes of colloidal lithography, which have great potential
      to replace, at least partially, complex and high-cost advanced lithographic
      techniques. This Review presents the state of the art of colloidal lithography
      and consists of three main parts, beginning with synthetic routes to monodisperse
      colloids and their self-assembly with low defect concentrations, which are used
      as lithographic masks. Then, we will introduce the modification of the colloidal
      masks using reactive ion etching (RIE), which produces a variety of nanoscopic
      features and multifaceted particles. Finally, a few prospective applications of
      colloidal lithography will be discussed.

PMID- 17193069
TI  - One-pot synthesis of CdTe nanocrystals and shape control of luminescent CdTe
      cystine nanocomposites.

PMID- 17193070
TI  - Easy writing of nanopatterns on a polymer film using electrostatic
      nanolithography.

PMID- 17193071
TI  - Ethylene glycol-protected magnetic nanoparticles for a multiplexed immunoassay in
      human plasma.

PMID- 17193072
TI  - Functionalization of carbon nanohorns with azomethine ylides: towards solubility
      enhancement and electron-transfer processes.

PMID- 17193073
TI  - Electrospun polymer nanofibers as subwavelength optical waveguides incorporating
      quantum dots.

PMID- 17193074
TI  - Variable size and shape distribution of ferroelectric nanoislands by chemical
      mechanical polishing.

PMID- 17193075
TI  - Facile self-assembly processes to phenylene-bridged silica monoliths with four
      levels of hierarchy.

PMID- 17193076
TI  - Nano-objects on a round trip from water to organics in a polymeric ionic liquid
      vehicle.

PMID- 17193077
TI  - Functionalized ZnO nanoparticles with liquidlike behavior and their
      photoluminescence properties.

PMID- 17193078
TI  - Surfactant-templated synthesis of 1D single-crystalline polymer nanostructures.

PMID- 17193079
TI  - Highly ordered anodic porous alumina with 13-nm hole intervals using a 2D array
      of monodisperse nanoparticles as a template.

PMID- 17193080
TI  - Directed synthesis and assembly of nanoparticles using purple membrane.

PMID- 17193081
TI  - Decoration of cowpea mosaic virus with multiple, redox-active, organometallic
      complexes.

PMID- 17193082
TI  - Coupling fluorescence correlation spectroscopy with microchip electrophoresis to
      determine the effective surface charge of water-soluble quantum dots.

PMID- 17193083
TI  - Electrospray ion beam deposition of clusters and biomolecules.
AB  - An ion beam source using electrospray ionization is presented for nondestructive
      vacuum deposition of mass-selected large organic molecules and inorganic
      clusters. Electrospray ionization is used to create an ion beam from a solution
      containing the nanoparticles or molecules to be deposited. To form and guide the
      ion beam, radio frequency and electrostatic ion optics are utilized. The kinetic
      energy distribution of the particles is measured to control the beam formation
      and the landing process. The particle mass-to-charge ratio is analyzed by in situ
      time-of-flight mass spectrometry. To demonstrate the performance of the setup,
      deposition experiments with gold nanoclusters and bovine serum albumin proteins
      on graphite surfaces were performed and analyzed by ex situ atomic force
      microscopy. The small gold clusters are found to form three-dimensional
      agglomerations at the surface, preferentially decorating the step edges. In
      contrast, bovine serum albumin creates two-dimensional fractal nanostructures on
      the substrate terraces due to strong intermolecular interactions.

PMID- 17193084
TI  - Conversion of a Bi nanowire array to an array of Bi-Bi2O3 core-shell nanowires
      and Bi2O3 nanotubes.
AB  - A template-based heat-treatment method has been developed to convert metal
      nanowire arrays into arrays of metal-metal oxide core-shell nanowires and single
      crystalline metal oxide nanotubes. This process is demonstrated by kinetically
      controlling the conversion of single-crystalline Bi nanowires to Bi-Bi(2)O(3)
      core-shell nanowires via a multistep, slow oxidation method, and then controlling
      their further conversion to a single-crystalline Bi(2)O(3) nanotube array via
      fast oxidation. This process can conveniently be extended to fabricate a free
      standing, easily oxidized metal-metal oxide nanowire and metal oxide nanotube
      array, which may have future applications in nanoscale optics, electronics, and
      magnetics.

PMID- 17193085
TI  - Dramatic effect of dispersed carbon nanotubes on the mechanical and
      electroconductive properties of polymers derived from ionic liquids.
AB  - Free-radical polymerization of an imidazolium ion-based ionic liquid bearing a
      methacrylate group, gelling with single-walled carbon nanotubes (SWNTs), allows
      fabrication of a mechanically reinforced, electroconductive soft material (bucky
      plastic). A film sample of this material displays an excellent conductivity of 1
      S cm(-1) and a 120-fold enhancement of the Young's modulus at a 7 wt % content of
      SWNTs. The conductivity is temperature-dependent in the range 5-300 K, suggesting
      that the conductive process involves carrier hopping. Scanning electron and
      atomic force micrographs of a bucky plastic film display the presence of
      crosslinked networks consisting of finely dispersed SWNTs. Such nanotube
      networks, developed in the polymer matrix, likely suppress slipping of entrapped
      polymer molecules via a strong interfacial interaction and also facilitate
      intertubular carrier transport. Although a bucky plastic derived from a
      vinylimidazolium ion-based ionic liquid monomer shows a comparable conductivity
      to that of the methacrylate version, the film is brittle irrespective of the
      presence or absence of SWNTs.

PMID- 17193086
TI  - Template-assisted large-scale ordered arrays of ZnO pillars for optical and
      piezoelectric applications.
AB  - Spatially separated ZnO pillars, typically 300 nm in diameter and 2 microm in
      height, are fabricated via a template-directed approach that leads to long-range
      hexagonal order. The templates of Au nanodisk arrays are obtained by using metal
      membranes as a lithography mask. The growth of ZnO pillars is performed in a
      double-tube system through vapor diffusion-deposition. The growth mechanism of
      the pillars is studied in detail and is proposed to be a combination of vapor
      liquid-solid and vapor-solid models. The piezoelectric and optical properties of
      single pillars are characterized using piezoresponse force microscopy and micro
      photoluminescence spectroscopy, respectively. The pillars show strong excitonic
      emissions up to room temperature, which indicate a relatively low defect density
      and good crystalline quality. The obtained piezoelectric coefficient d(33) is
      (7.5+/-0.6) pm V(-1), which is to our knowledge the first reported value for a
      single nanopillar.

PMID- 17193087
TI  - Surface nanopatterning by organic/inorganic self-assembly and selective local
      functionalization.
AB  - Patterning silicon surfaces by well-ordered nanoperforated TiO(2) layers is
      achieved through a simple block copolymer-assisted liquid deposition technique
      followed by direct thermal treatment. The crater diameters are tuned between 10
      and 50 nm, depending on the molecular weight of the surfactant patterning agent.
      The formation mechanism of such systems is discussed. The present nanopatterned
      heterogeneous surfaces (nanoholes with SiO(2) bottom surfaces and TiO(2) walls)
      are selectively functionalized with two different perfluorinated organic groups.
      The accessibility to the substrate surface through such nanoholes and the
      selective distribution of both functions on the surface is evidenced by water
      contact-angle measurements, which satisfactorily verify the Cassie relationship.
      Such systems have wide application prospects in varied fields such as
      nanotechnology and engineering.

PMID- 17193093
TI  - Anisotropically phase-separated biphasic particles.

PMID- 17193094
TI  - Controlled arrangement of nanoparticle arrays in block-copolymer domains.
AB  - This Review describes recent results on the precise spatial distribution control
      of metal and semiconductor nanoparticles into domains of microphase-separated
      block copolymers. Specific focus is directed towards selective incorporation into
      a specific microphase of a block copolymer. Details on theoretical aspects
      concerning nanoparticle incorporation as well as practical examples are given.
      Furthermore, examples on applications and technological aspects of the resulting
      nanoparticle/polymer nanocomposites are provided.

PMID- 17193095
TI  - Synthesis of ultrathin ZnO nanofibers aligned on a zinc substrate.

PMID- 17193096
TI  - Nanosized CuO particles via a supramolecular strategy.

PMID- 17193097
TI  - Three-dimensional functionalized tetrapod-like ZnO nanostructures for plasmid DNA
      delivery.

PMID- 17193098
TI  - Transport of semiconductor nanocrystals by kinesin molecular motors.

PMID- 17193099
TI  - Fluorescent image correlation for nanoscale deformation measurements.

PMID- 17193100
TI  - Shape-dependent plasmon-resonant gold nanoparticles.

PMID- 17193101
TI  - Rapid, room-temperature synthesis of antibacterial bionanocomposites of lysozyme
      with amorphous silica or titania.

PMID- 17193102
TI  - Visualization of size-selective protein separations on spherical mesoporous
      silicates.

PMID- 17193103
TI  - Tuning the size and optical properties in molecular nano/microcrystals:
      manifestation of hierarchical interactions.
AB  - Intermolecular interactions, such as hydrogen bonding, dipolar and van der Waals,
      occurring in molecular crystals cover a range of magnitudes. As the crystal
      evolves from a relatively softer state in the nanoscopic size regime to a harder
      one in the microcrystalline and bulk solid state, the impact of the hierarchy of
      intermolecular interactions can be expected to emerge in a progressive fashion.
      The strongest interactions alone would be manifested at small sizes; as the
      crystal grows, the effect of the weaker ones will be added on, with the bulk
      crystals exhibiting the cumulative impact of the different interactions. We
      demonstrate this phenomenon through investigations of the solution, colloid, and
      solid state of a novel zwitterionic molecule based on the
      diaminodicyanoquinodimethane framework. A reprecipitation-digestion protocol is
      developed for the fabrication of nano/microcrystals of varying sizes. Microscopic
      and spectroscopic characterizations reveal tuning of the size and optical
      properties of this material. The optical absorption of the colloidal particles
      evolves with size towards that of the bulk solid, the emission showing a steady
      enhancement of intensity. Crystallographic investigations coupled with
      semiempirical computations provide a viable model to describe the range of
      observations in terms of the gradual accumulation of hierarchical intermolecular
      interactions.

PMID- 17193104
TI  - Mechanical properties of organic nanofibers.
AB  - Intrinsic elastic and inelastic mechanical properties of individual, self
      assembled, quasi-single-crystalline para-hexaphenylene nanofibers supported on
      substrates with different hydrophobicities are investigated as well as the
      interplay between the fibers and the underlying substrates. We find from atomic
      force-microscopy-based rupture experiments a rupture shear stress of about 2 x
      10(7) Pa for an individual fiber. Deflecting a nanofiber suspended across a gap
      results in a Young's modulus of 0.65 GPa. Translational motion of intact
      nanofibers across the surface is demonstrated for fibers on a silicon substrate
      with a low-adhesion coating, whereas such motion on a noncoated substrate is
      limited to very short (sub-micrometer) nanofiber pieces due to strong adhesive
      forces.

PMID- 17193105
TI  - In situ Raman study on single- and double-walled carbon nanotubes as a function
      of lithium insertion.
AB  - We investigated the electrochemical lithium ion (Li(+)) insertion/desertion
      behavior on highly pure and bundled single- and double-walled carbon nanotubes
      (SWNTs and DWNTs) using an in situ Raman technique. In general, two storage sites
      could host Li(+) in SWNT and DWNT bundles when varying an external potential: a)
      the outer surface sites, and b) the interstitial spaces within the bundles. The
      most sensitive changes in the tangential mode (TM) of the Raman spectra upon
      doping with Li(+) can be divided into two regions. The first region was found
      from 2.8 to 1.0 V (the coverage of Li(+) on the outer surface of a bundled
      nanotube) and was characterized by the loss of resonant conditions via partial
      charge transfer, where the G(+) line of the SWNT and the TM of the outer tube of
      DWNTs experienced a highly depressed intensity, but remained almost constant in
      frequency. The appearance of a Breit-Wigner-Fano (BWF) profile provided strong
      evidence of metallic inner tubes within DWNTs. The second region was observed
      when the applied potentials ranged from 0.9 to 0 V and was characterized by Li(+)
      diffusion into the interstitial sites of the bundled nanotube material. This
      phenomenon invoked a large downshift of the G(-) band in SWNTs, and a small
      downshift of the TM of the inner tube of DWNTs caused by expansion of the C--C
      bonds due to the charge transferred to the nanotubes, and the disappearance of
      the BWF profile through the screening effect of the interstitial Li(+) layers.

PMID- 17193109
TI  - Semiconductor nanowires: from self-organization to patterned growth.
AB  - The synthesis of semiconductor nanowires has been studied intensively worldwide
      for a wide spectrum of materials. Such low-dimensional nanostructures are not
      only interesting for fundamental research due to their unique structural and
      physical properties relative to their bulk counterparts, but also offer
      fascinating potential for future technological applications. Deeper understanding
      and sufficient control of the growth of nanowires are central to the current
      research interest. This Review discusses the various growth processes, with a
      focus on the vapor-liquid-solid process, which offers an opportunity for the
      control of spatial positioning of nanowires. Strategies for position-controlled
      and nanopatterned growth of nanowire arrays are reviewed and demonstrated by
      selected examples as well as discussed in terms of larger-scale realization and
      future prospects. Issues on building up nanowire-based electronic and photonic
      devices are addressed at the end of the Review, accompanied by a brief survey of
      recent progress demonstrated so far on the laboratory level.

PMID- 17193110
TI  - In vitro transcription and protein translation from carbon nanotube-DNA
      assemblies.

PMID- 17193111
TI  - Core/Shell fluorescent silica nanoparticles for chemical sensing: towards single
      particle laboratories.

PMID- 17193112
TI  - Self-assembly of copper micro/nanoscale parallel wires by electrodeposition on a
      silicon substrate.

PMID- 17193113
TI  - Experimental evidence of an octahedron nucleus in ZnS tetrapods.

PMID- 17193114
TI  - Enhanced secondary electron emission from group III nitride/ZnO coaxial nanorod
      heterostructures.

PMID- 17193115
TI  - Quantum dots on gold: electrodes for photoswitchable cytochrome C
      electrochemistry.

PMID- 17193116
TI  - Local secondary-electron emission spectra via scanning probe energy loss
      spectroscopy.

PMID- 17193117
TI  - Facile one-pot synthesis of luminescent, water-soluble, and biocompatible
      glutathione-coated CdTe nanocrystals.

PMID- 17193118
TI  - Solid-state synthesis of well-defined carbon nanocapsules from organometallic
      precursors.

PMID- 17193120
TI  - Patterning of chemical gradients with submicrometer resolution using edge
      spreading lithography.

PMID- 17193119
TI  - Structural effects of iron oxide nanoparticles and iron ions on the hydrothermal
      carbonization of starch and rice carbohydrates.

PMID- 17193121
TI  - Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts.
AB  - Nanoscale engineering is one of the most dynamically growing areas at the
      interface between electronics, physics, biology, and medicine. As there are no
      safety regulations yet, concerns about future health problems are rising. We
      investigated the effects of citrate/gold nanoparticles at different
      concentrations and exposure times on human dermal fibroblasts. We found that, as
      a result of intracellular nanoparticle presence, actin stress fibers disappeared,
      thereby inducing major adverse effects on cell viability. Thus, properties such
      as cell spreading and adhesion, cell growth, and protein synthesis to form the
      extracellular matrix were altered dramatically. These results suggest that the
      internal cell activities have been damaged.

PMID- 17193122
TI  - Crystallographic order in multi-walled carbon nanotubes synthesized in the
      presence of nitrogen.
AB  - Multi-walled carbon nanotubes were synthesized by chemical vapor deposition from
      pure toluene and toluene/diazine mixtures using ferrocene as a catalyst precursor
      at 760 degrees C. As recently announced, characterization of the resulting
      nanotube films showed that, unlike pure carbon nanotubes, those grown in the
      presence of nitrogen have an extremely high degree of internal order, both in
      terms of the uniform chirality in the nanotube walls and of the crystallographic
      register between them. Here, the structure, defects, and morphology of the
      nanotubes were analyzed in depth using advanced electron microscopy techniques,
      and compared with existing models and observations. Nitrogen, which seems to be
      responsible for the dramatic structural order, was found to segregate
      preferentially within the core of the nanotubes.

PMID- 17193123
TI  - Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR
      imaging and drug delivery.
AB  - We report the development of a biostable methotrexate-immobilized iron oxide
      nanoparticle drug carrier that may potentially be used for real-time monitoring
      of drug delivery through magnetic resonance imaging. Methotrexate (MTX) was
      immobilized on the nanoparticle surface via a poly(ethylene glycol) self
      assembled monolayer (PEG SAM). The cytotoxicity of the nanoparticle-drug
      conjugate (NP-PEG-MTX) to target cells was studied with 9L glioma cells. Cellular
      uptake experiments showed that the uptake of NP-PEG-MTX conjugates by glioma
      cells was considerably higher than that of control nanoparticles. Magnetic
      resonance imaging in 9L cells cultured with NP-PEG-MTX of various concentrations
      showed significant contrast enhancement. NP-PEG-MTX demonstrated higher
      cytotoxicity in 9L cells to free MTX in vitro. Leucovorin, an MTX antidote, was
      used to rescue the cells that had been exposed to NP-PEG-MTX or free MTX, and the
      experiment verified the biocompatibility of NP-PEG-MTX conjugates and the MTX on
      NP-PEG-MTX conjugates to be the true source of the cytotoxicity to the target
      cells. TEM results showed that NP-PEG-MTX conjugates were internalized into the
      9L cellular cytoplasm and retained its crystal structure therein for up to 144 h,
      as identified by electron diffraction. This prolonged particle retention may
      allow physicians to image tumor cells exposed to the NP-PEG-MTX conjugate over an
      extended therapeutic time course.

PMID- 17193124
TI  - The stability and functionality of chemically crosslinked microtubules.
AB  - A variety of bifunctional crosslinking agents have been explored for stabilizing
      microtubule shuttles used for the active transport of nanomaterials in artificial
      environments. Crosslinking agents that target amine residues form intertubulin
      crosslinks that produce crosslinked microtubules (CLMTs) with structural and
      functional lifetimes that can be up to four times as long as those achieved with
      taxol stabilization. Such CLMTs are stable at temperatures down to -10 degrees C,
      are resistant to depolymerization induced by metal ions such as Ca2+, and yet
      continue to be adsorbed and transported by self-assembled monolayers containing
      the motor protein kinesin. However, crosslinkers that target cysteine residues
      depolymerize the MTs, probably by interfering with the guanosine triphosphate
      binding site. The impact of crosslink attributes, including terminal group
      chemistry, chain length, crosslink density, and specific location on the tubulin
      surface, on microtubule stability and functionality are discussed.

PMID- 17193129
TI  - Surface-tension-driven patterning: combining tailored physical self-organization
      with microfabrication methods.

PMID- 17193125
TI  - Room-temperature ferromagnetism in doped face-centered cubic fe nanoparticles.
AB  - The magnetism of Fe and its alloys has been at the center of scientific and
      technological interest for decades. Along with the ferromagnetic nature of body
      centered cubic Fe, the magnetic properties of face-centered cubic (fcc) Fe have
      attracted much attention. It is well known that fcc Fe is thermodynamically
      unstable at ambient conditions and not ferromagnetic. Contrary to what is known,
      we report that elongated nanoparticles of fcc Fe, grown within graphitic
      nanotubes, remain structurally stable and appear ferromagnetic at room
      temperature. The magnetic moment (2+/-0.5 microB) in these nanoparticles and the
      hyperfine fields for two different components of 57Fe (33 and 21 T), measured by
      Mossbauer spectroscopy, are explained by carbon interstitials in the expanded fcc
      Fe lattice, that is, FeC(x) where x approximately 0.10, which result in the
      formation of a dominant Fe4C stoichiometry. First-principles calculations suggest
      that the ferromagnetism observed in the fcc Fe is related to both lattice
      expansion and charge transfer between iron and carbon. The understanding of
      strain- and dopant-induced ferromagnetism in the fcc Fe could lead to the
      development of new fcc Fe-based alloys for magnetic applications.

PMID- 17193130
TI  - NaNaX 2: a conference devoted to "nanoscience with nanocrystals".

PMID- 17193131
TI  - Microchip technology for automated and parallel patch-clamp recording.
AB  - The patch-clamp technique is the state-of-the-art technology for the study of a
      large class of membrane proteins called ion channels. Ion channels mediate
      electrical current flow, have crucial roles in cellular physiology, and are
      important drug targets. However, patch clamping is a laborious process requiring
      a skilled experimenter and is, therefore, not compatible with the high throughput
      needed in drug development. The solution for automated and parallel patch-clamp
      measurements that is provided by microchip technology is presented here.

PMID- 17193132
TI  - Nanopatterned polymer brushes by combining AFM anodization lithography with ring
      opening metathesis polymerization in the liquid and vapor phase.

PMID- 17193133
TI  - Fabrication of jingle-bell-shaped core-shell nanoparticulate films and molecular
      size-responsive photoluminescence quenching of cadmium sulfide cores.

PMID- 17193134
TI  - Preparation of monodisperse, submicrometer carbon spheres by pyrolysis of
      melamine-formaldehyde resin.

PMID- 17193135
TI  - Dendrite-like self-assembly of magnetite nanoparticles on porous silicon.

PMID- 17193136
TI  - pH-selective synthesis of monodisperse nanoparticles and 3D dendritic
      nanoclusters of CTAB-stabilized platinum for electrocatalytic O2 reduction.

PMID- 17193137
TI  - Cation-controlled aqueous dispersions of alginic-acid-wrapped multi-walled carbon
      nanotubes.

PMID- 17193138
TI  - A strategy for the synthesis of transition-metal nanoparticles and their transfer
      between liquid phases.

PMID- 17193139
TI  - A simple miniaturization protocol to produce multicomponent micro- and
      nanostructures.

PMID- 17193140
TI  - Self-organization of anodic nanotubes on two size scales.

PMID- 17193141
TI  - Nanotemplated crystallization of organic molecules.

PMID- 17193142
TI  - Incorporating CdTe nanocrystals into polystyrene microspheres: towards robust
      fluorescent beads.

PMID- 17193143
TI  - Critical oxide thickness for efficient single-walled carbon nanotube growth on
      silicon using thin SiO2 diffusion barriers.
AB  - The ability to integrate carbon nanotubes, especially single-walled carbon
      nanotubes, seamlessly onto silicon would expand their range of applications
      considerably. Though direct integration using chemical vapor deposition is the
      simplest method, the growth of single-walled carbon nanotubes on bare silicon and
      on ultrathin oxides is greatly inhibited due to the formation of a noncatalytic
      silicide. Using X-ray photoelectron spectroscopy, we show that silicide formation
      occurs on ultrathin oxides due to thermally activated metal diffusion through the
      oxide. Silicides affect the growth of single-walled nanotubes more than multi
      walled nanotubes due to the increased kinetics at the higher single-walled
      nanotube growth temperature. We demonstrate that nickel and iron catalysts, when
      deposited on clean silicon or ultrathin silicon dioxide layers, begin to form
      silicides at relatively low temperatures, and that by 900 degrees C, all of the
      catalyst has been incorporated into the silicide, rendering it inactive for
      subsequent single-walled nanotube growth. We further show that a 4-nm silicon
      dioxide layer is the minimum diffusion barrier thickness that allows for
      efficient single-walled nanotube growth.

PMID- 17193144
TI  - Simple method for the stretching and alignment of single adsorbed synthetic
      polycations.
AB  - Spin-coating of isolated positively charged macromolecules onto mica in the
      presence of octylamine was found to be a simple and general method of stretching
      and aligning the macromolecular chains. The contour length and molar mass for the
      stretched macromolecules can be directly measured by atomic force microscopy,
      which makes this method a very useful analytical tool. Moreover, the molecular
      height is increased by co-deposition with octylamine, which drastically improves
      the molecular resolution and allows even ultrathin polycations to be visualized.
      The reason for the key role of the octylamine is found in the formation of an
      ultrathin liquidlike alkylamine film, which reduces the surface energy of mica
      and weakens the interactions between the surface and the charged macromolecules.

PMID- 17193145
TI  - Thermosensitive Y-shaped micelles of poly(oleic acid-Y-N-isopropylacrylamide) for
      drug delivery.
AB  - A novel thermosensitive amphiphilic copolymer comprised of two hydrophobic
      poly(oleic acid) (POA) segments and one hydrophilic poly(N-isopropylacrylamide)
      (PNIPAAm) segment was designed and synthesized. The structure of the copolymer
      was confirmed as Y-shaped by FTIR, 1H NMR, and SEC-MALLS analysis. A cytotoxicity
      study shows that the P(OA-Y-NIPAAm) copolymer exhibits good biocompatibility. The
      copolymer may self-assemble into micelles in water, with the hydrophobic POA
      segments at the cores of micelles and the hydrophilic PNIPAAm segments as the
      outer shells. The resulting micelles demonstrate temperature sensitivity with a
      lower critical solution temperature (LCST) of 31.5 degrees C and a critical
      micelle concentration (CMC) of 12.6 mg L(-1). Transmission electron microscopy
      (TEM) shows that the micelles exhibit a nanospheric morphology within a narrow
      size range of approximately 10-30 nm. A study of controlled release reveals that
      the self-assembled micelles have great potential as drug carriers.

PMID- 17193149
TI  - Optical properties of ZnO nanostructures.
AB  - We present a review of current research on the optical properties of ZnO
      nanostructures. We provide a brief introduction to different fabrication methods
      for various ZnO nanostructures and some general guidelines on how fabrication
      parameters (temperature, vapor-phase versus solution-phase deposition, etc.)
      affect their properties. A detailed discussion of photoluminescence, both in the
      UV region and in the visible spectral range, is provided. In addition, different
      gain (excitonic versus electron hole plasma) and feedback (random lasing versus
      individual nanostructures functioning as Fabry-Perot resonators) mechanisms for
      achieving stimulated emission are described. The factors affecting the
      achievement of stimulated emission are discussed, and the results of time
      resolved studies of stimulated emission are summarized. Then, results of
      nonlinear optical studies, such as second-harmonic generation, are presented.
      Optical properties of doped ZnO nanostructures are also discussed, along with a
      concluding outlook for research into the optical properties of ZnO.

PMID- 17193150
TI  - Controlled ligand display on a symmetrical protein-cage architecture through
      mixed assembly.

PMID- 17193151
TI  - Submicrometer pore-based characterization and quantification of antibody-virus
      interactions.

PMID- 17193152
TI  - Reversible and controllable switching of a single-molecule junction.

PMID- 17193153
TI  - Wafer-scale Ni imprint stamps for porous alumina membranes based on interference
      lithography.

PMID- 17193154
TI  - A macrophage-targeted theranostic nanoparticle for biomedical applications.

PMID- 17193155
TI  - Carbon nanotube macrobundles for light sensing.

PMID- 17193156
TI  - Hierarchically structured ceramics by high-precision nanoparticle casting of
      wood.

PMID- 17193158
TI  - Ultrathin fullerene films as high-resolution molecular resists for low-voltage
      electron-beam lithography.

PMID- 17193157
TI  - Use of ester-terminated polyamidoamine dendrimers for stabilizing quantum dots in
      aqueous solutions.

PMID- 17193159
TI  - Fabrication of electrically bistable nanofibers.

PMID- 17193160
TI  - Gold-conjugated protein nanoarrays through block-copolymer lithography: from
      fabrication to biosensor design.

PMID- 17193161
TI  - Membrane stiffness of animal cells challenged by osmotic stress.

PMID- 17193162
TI  - Inkjet printing of electrically conductive patterns of carbon nanotubes.

PMID- 17193163
TI  - In-plane large single-walled carbon nanotube films: in situ synthesis and field
      emission properties.

PMID- 17193164
TI  - Nanotube coalescence-inducing mode: a novel vibrational mode in carbon systems.

PMID- 17193165
TI  - Pt nanoparticles functionalized with nucleic acid act as catalytic labels for the
      chemiluminescent detection of DNA and proteins.

PMID- 17193166
TI  - Metallic nanoparticles hosted in mesoporous oxide thin films for catalytic
      applications.

PMID- 17193167
TI  - Shape-controlled growth of micrometer-sized gold crystals by a slow reduction
      method.

PMID- 17193168
TI  - Carbon microfibers sheathed with aligned carbon nanotubes: towards
      multidimensional, multicomponent, and multifunctional nanomaterials.
AB  - Multicomponent and multifunctional hybrid structures based on microsized carbon
      fibers sheathed with aligned carbon nanotubes and their derivatives have been
      successfully prepared, and have been demonstrated to be an effective means for
      connecting nanoscale entities to the outside world and to possess interesting
      electrochemical properties attractive for a wide range of potential applications,
      including in methanol direct fuel cells and highly sensitive biological and
      chemical sensors. Judicious modification of the carbon-fiber-supported aligned
      carbon nanotubes with various functional moieties could lead to a class of novel
      multidimensional, multicomponent, and multifunctional materials of practical
      significance.

PMID- 17193169
TI  - Phantom nanoparticles as probes of biomolecular interactions.
AB  - A new light-scattering-based method to detect molecular interactions at the
      surface of low-refractive-index nanoparticles was recently proposed. Water
      dispersed nanoparticles functionalized with receptors typical of immature
      bacteria cell walls were used to study the activity of the antibiotic vancomycin.
      This method subtly depends on the specific properties of the nanoparticles. Here
      we discuss, by comparative experiments and through theoretical evaluation, the
      effects of size, refractive index, electric charge, and dilution on the
      reliability and accuracy of the method. Quite surprisingly, perfect index
      matching and minimal size (i.e., maximum surface), which is almost attained in
      one of the colloids here employed, do not represent the ideal conditions. Rather,
      we show that a nanoparticle radius of 100 nm and a refractive index slightly
      below that of water yields the best signal/background amplitude. We also show
      that repulsive interactions can lead to artifacts in the adsorption isotherm,
      thus indicating that electrostatic stabilization should be kept at a minimum. The
      close agreement between the interaction strengths, as measured with two different
      nanoparticle systems, testifies to the reliability of the method.

PMID- 17193170
TI  - Soft lithographic printing of patterns of stretched DNA and DNA/electronic
      polymer wires by surface-energy modification and transfer.
AB  - Aligned and stretched lambda DNA is directed to specific locations on solid
      substrates. Surface-energy modification of glass substrates by using patterned
      polydimethylsiloxane (PDMS) stamps is used to direct DNA onto the surface-energy
      modified micrometer-scale pattern through molecular combing. As an alternative,
      patterned and nonpatterned PDMS stamps modified with polymethylmethacrylate
      (PMMA) are utilized to direct the stretched DNA to the desired location and the
      results are compared. The DNA is elongated through molecular combing on the stamp
      and transfer printed onto the surfaces. PMMA-modified stamps show a more defined
      length of the stretched DNA, as compared to bare PDMS stamps. A combination of
      these two methods is also demonstrated. As an application example, transfer
      printing of DNA decorated with a semiconducting conjugated polyelectrolyte is
      shown. The resulting patterned localization of stretched DNA can be utilized for
      functional nanodevice structures, as well as for biological applications.

PMID- 17193171
TI  - Electrochemically functionalized carbon nanotubes and their application to
      rechargeable lithium batteries.
AB  - Electrochemical polymerization of N-vinyl carbazole (VC) on carbon nanotube (CNT)
      films was studied by cyclic voltammetry (CV) in LiClO4/acetonitrile solutions.
      Comparing the cyclic voltammograms recorded on a blank Pt electrode with those
      obtained when single- or multi-walled carbon nanotube (SWNT or MWNT) films were
      previously deposited onto the Pt electrode, a downshift of the VC reduction peak
      potential is observed in the latter case. The influences of monomer
      concentration, type of solvent, and supporting electrolyte on the polymerization
      conditions and electrochemical properties of these composite materials are also
      investigated. The morphological aspects of poly(N-vinyl carbazole) (PVC)
      functionalized CNTs are revealed by transmission electron microscopy (TEM)
      studies. A covalent functionalization of carbon nanotubes with PVC is invoked as
      a result of attenuated total reflection infrared (ATR-IR) spectroscopic studies.
      Using PVC-functionalized CNTs as a positive electrode and an electrolytic
      solution containing LiPF6, the charge-discharge characteristics of the
      rechargeable lithium cells are determined. High specific discharge capacity
      (approximately 45 and 115 mA h g(-1)) is reported for PVC-functionalized single-
      and multi-walled carbon nanotubes, respectively.

PMID- 17193172
TI  - A single-molecule Forster resonance energy transfer analysis of fluorescent DNA
      protein conjugates for nanobiotechnology.
AB  - The development of nanobiotechnological devices requires the ability to build
      various components with nanometer accuracy. DNA is a well-established nanoscale
      building block that self assembles due to specific interactions that are encoded
      in its sequence. Recently, it has become possible to couple proteins to DNA,
      thereby expanding the capabilities of DNA for use with molecular photonics and
      bioelectronics. Here, we present the design and characterization of a
      supramolecular Forster resonance energy transfer (FRET) system by using a
      fluorescent protein bound to single-stranded DNA (ssDNA), a fluorophore attached
      to a second ssDNA molecule, and a complementary strand for hybridizing the two
      fluorophores together. The FRET efficiency was studied by using both ensemble and
      single-pair FRET measurements. The distance between the two fluorophores was
      determined from the single-pair FRET efficiency and could be described by a
      simple cylindrical model for the DNA. Hence, DNA can be used as a scaffold for
      positioning fluorescent proteins, as well as traditional fluorophores, with
      nanometer accuracy and shows great potential for use in the future of
      nanobiotechnology.

PMID- 17193173
TI  - Parallel manipulation of bifunctional DNA molecules on structured surfaces using
      kinesin-driven microtubules.
AB  - We have developed a technique to manipulate bifunctional DNA molecules: One end
      is thiolated to bind to a patterned gold surface and the other end is
      biotinylated to bind to a microtubule gliding over a kinesin-coated surface. We
      found that DNA molecules can be stretched and overstretched between the gold pads
      and the motile microtubules, and that they can form dynamic networks. This serves
      as a proof-of-principle that biological machineries can be used in vitro to
      accomplish the parallel formation of structured DNA templates that will have
      applications in biophysics and nanoelectronics.

PMID- 17193175
TI  - 'Five at one stroke': proline and small peptides in the stereoselective de novo
      synthesis and enantiotopic functionalization of carbohydrates.
AB  - Asymmetric catalysis with the simple amino acid proline (so called 'enamine
      catalysis') arrested big attention in the last few years since the re-discovery
      of the Hajos-Parrish-Eder-Sauer-Wiechert reaction. After basic mechanistic
      studies, probing scope and limitations of the catalyst and the corresponding
      reactions, this concept has now emerged to a state where it is applied to the
      assembly of up to five stereogenic centers of carbohydrates, not really 'at one
      stroke', but in only two simple synthetic operations. Beyond, it is not only
      possible to build up complicated natural products elegantly, but also to address
      selectively the similar functional groups of carbohydrates by small peptidic
      catalysts. This short review covers the recent developments of organocatalysis in
      both fields, with special emphasis on the asymmetric assembly and selective
      derivatization of carbohydrates.

PMID- 17193176
TI  - Volatiles released by a Streptomyces species isolated from the North Sea.
AB  - The North Sea Streptomyces strain GWS-BW-H5 was investigated by analyzing
      headspace extracts of agar-plate cultures (HE) or liquid cultures (LCE), obtained
      with a closed-loop stripping apparatus (CLSA), by GC/MS (Table 1). The volatile
      profile of the HE is dominated by the known volatiles (-)-geosmin (4) and 2
      methyisoborneol (1). Small amounts of sesquiterpenes occur, which are present in
      a more-diverse structural variety and in higher quantities in the LCE. The
      different structures can be rationalized by few cationic intermediates along
      their biosynthetic pathway. The most-prominent difference between the two culture
      methods were the presence of the Me-branched gamma- and delta-lactones 31-38, not
      previously reported from nature, in the LCE. Major components were 10
      methyldodecan-5-olide (34), 10-methyldodec-2-en-4-olide (36), and 10-methyldodec
      3-en-4-olide (38). The structures of all new lactones were verified by synthesis.
      Furthermore, more volatiles in higher amounts were produced by the liquid culture
      than by to the agar plate culture. Since 36 showed inhibitory growth effects
      against strain GWS-BW-H5, growth inhibition against twelve other strains isolated
      from the same habitat was tested. Antagonistic activity against four of the
      strains was observed, with a slightly higher threshold level than found for
      penicillin G, which was used in control experiments (Table 2).

PMID- 17193177
TI  - Two new pregnanone derivatives with strong cytotoxic activity from Pachysandra
      axillaris.
AB  - Two new, bioactive, pregnane-based natural products, pachysanonin (=
      3beta,11alpha,12beta)-12-acetoxy-3-(dimethylamino)-11-[(3,4-dimethylpent-3
      enoyl)oxy]pregnan-20-one; 1) and pachysanone (= (11alpha,12beta)-12-acetoxy-11
      [(3,4-dimethylpent-3-enoyl)oxy]pregnan-3,20-dion; 2) have been isolated from
      Pachysandra axillaris. Their structures were determined by spectroscopic methods,
      and, in the case of 2, by single-crystal X-ray crystallography (Figure). Compound
      2 showed significant antitumor activity against Lewis lung carcinoma (LCC) tumor
      cells, with an IC50 value of 0.020+/-0.006 microg/ml, which is equal or even
      lower than those of the well-known natural antitumor agents harringtonine (0.02),
      homoharringtonine (0.15), and adriamycin (0.06 microg/ml; positive control).

PMID- 17193178
TI  - Predicting drug metabolism--an evaluation of the expert system METEOR.
AB  - The paper begins with a discussion of the goals of metabolic predictions in early
      drug research, and some difficulties toward this objective, mainly the various
      substrate and product selectivities characteristic of drug metabolism. The major
      in silico approaches to predict drug metabolism are then classified and
      summarized. A discrimination is, thus, made between 'local' and 'global' systems.
      In its second part, an evaluation of METEOR, a rule-based expert system used to
      predict the metabolism of drugs and other xenobiotics, is reported. The published
      metabolic data of ten substrates were used in this evaluation, the overall
      results being discussed in terms of correct vs. disputable (i.e., false-positive
      and false-negative) predictions. The predictions for four representative
      substrates are presented in detail (Figs. 1-4), illustrating the interest of such
      an evaluation in identifying where and how predictive rules can be improved.

PMID- 17193179
TI  - The furoxan system: design of selective nitric oxide (NO) donor inhibitors of COX
      2 endowed with anti-aggregatory and vasodilating activities.
AB  - Several NO donor 3,4-diphenylfuroxan (= 3,4-diphenyl-1,2,5-oxadiazole 2-oxide)
      derivatives were synthesized and tested for their COX-inhibiting activities. The
      products were found to be selective COX-2 inhibitors, similar to the structurally
      related furazans (3,4-diphenyl-1,2,5-oxadiazole), devoid of the NO release
      property. This behavior was confirmed by a molecular-docking study. The NO
      dependent platelet anti-aggregatory and vasodilating activities of the new
      furoxans 5-7 were studied in vitro. These properties can be modulated by
      inserting an appropriate spacer between the 4-phenyl group and the furoxan ring,
      giving rise to new, selective COX-2 furoxan derivatives endowed with anti
      aggregatory and vasodilating activities, and with potentially reduced
      cardiotoxicities.

PMID- 17193180
TI  - Marine polyprenylated hydroquinones, quinones, and chromenols with inhibitory
      effects on leukotriene formation.
AB  - A series of polyprenylated hydroquinones, quinones, and chromenols were isolated
      from the extracts of the marine sponge Ircinia spinosula and the brown alga
      Taonia atomaria, which gave rise to the constituents 1-4 and 5-8, respectively.
      Compounds 1, 2, 6, and 7 are new natural products, which were fully
      characterized. Their anti-inflammatory activities in terms of leukotriene
      formation were evaluated in an in vitro assay with pork leukocytes. The new
      hydroxylated compound, 2'-[28-hydroxy]heptaprenyl-1',4'-hydroquinone (= 2
      [(2E,6E,10E,14E,18Z,22E)-19-(hydroxymethyl)-3,7,11,15,23,27-hexamethyloctacosa
      2,6,10,14,18,22,26-heptaen-1-yl]benzene-1,4-diol; 1), the known tetraprenyl
      benzoquinone sargaquinone (5), and the known polyprenyl chromenols 3 and 4
      exhibited the highest anti-inflammatory activities, with IC50 values of 1.9-9.4
      microM (Table 3). Potential structure-activity relationships (SAR) are discussed.

PMID- 17193181
TI  - Characterization and bioscreening of a new triterpenoid and a flavanone isolated
      from Salvia nubicola.
AB  - A new epimeric lupane triterpenoid, 3alpha-hydroxy-20-oxo-30-norlupane (1), and a
      new flavanone (nubatin; 3) have been isolated from Salvia nubicola collected from
      Quetta, Pakistan. The structures of these constituents were elucidated with the
      aid of spectroscopic techniques, including two-dimensional NMR and NOE
      experiments. Both the metabolites were found to be moderately bio-active.

PMID- 17193182
TI  - Phytochemical evaluation of selected antioxidant-containing medicinal plants for
      use in the preparation of a herbal formula--a preliminary study.
AB  - Oxidative damage is implicated in the pathogenesis of a number of diseases.
      Scientific research shows positive links between accumulated free-radical damage
      and age-related diseases such as atherosclerosis, Alzheimer, and osteoarthritis.
      There are reports that plant-derived phenolic compounds such as flavonoids have
      antioxidant properties capable of reducing the risk of developing these diseases.
      This work aims to evaluate the antioxidant activity of selected medicinal plants
      traditionally used by herbalists, in particular for the treatment of arthritis,
      with a view to developing a formula for treating age and age-related diseases.
      Thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC)
      analyses of each plant confirmed the presence of a number of flavonoids reported
      in the literature, as well as unidentified compounds. The antioxidant activities
      of these plants were determined by DPPH (= '1,1-diphenyl-2-picryl-hydrazyl')
      radical scavenging, and by inhibition of linoleic acid peroxidation. All the
      crude plant extracts showed marked antioxidant activities in both assays. The
      extracts' inhibitory effects on linoleic acid peroxidation was concentration
      dependent, with the highest activity shown at 0.1% (w/v). These results suggest
      that the phenolic compounds, particularly the flavonoids, may, in part, be
      responsible for the antioxidant activity of traditional plant extracts.

PMID- 17193183
TI  - A potential prebiotic route to adenine from hypoxanthine.
AB  - A possible reaction mechanism for the dehydration of glycinamide (3) and N,N'
      diformylurea (4) yielding hypoxanthine (2) has been investigated. Furthermore, a
      potential prebiotic route converting hypoxanthine (2) into adenine (1) via
      phosphate activation followed by substitution reaction with NH3 was studied. This
      reaction mimics the proposed biochemical mechanism for the conversion of IMP to
      AMP.

PMID- 17193184
TI  - Isolation and structure elucidation of anhydroluteins from cooked sorrel (Rumex
      rugosus Campd.).
AB  - Anhydrolutein I (= (all-E,3R,6'R)-3',4'-didehydro-beta,gamma-caroten-3-ol; 2) and
      anhydrolutein II (= (all-E, 3R,6'S)-2',3'-didehydro-beta,epsilon-caroten-3-ol; 3)
      have been isolated and characterized from the extract of steam-cooked sorrel. The
      presence of these compounds in cooked vegetable is postulated to be due to acid
      catalyzed dehydration of lutein (1; Scheme). The structures of the isolated
      anhydroluteins were established by UV/VIS, CD, and 1H-NMR spectroscopy, and mass
      spectrometry.

PMID- 17193186
TI  - Radical-scavenging activities of new hydroxylated ursane triterpenes from cv.
      Annurca apples.
AB  - Two new ursolic acid triterpene derivatives, compounds 2 and 3, have been
      isolated from cv. Annurca apple fruit, a high-quality apple variety widely
      cultivated in southern Italy, together with the known 2-oxopomolic acid (1). The
      new compounds were identified by means of different spectroscopic techniques as 3
      epi-2-oxopomolic acid (= (3alpha)-3,19-dihydroxy-2-oxours-12-en-28-oic acid; 2)
      and (1alpha)-1-hydroxy-3-oxours-12-en-28-oic acid (3). Compounds 1-3 were tested
      for their radical-scavenging activities with the aid of a 1,1-diphenyl-2
      picrylhydrazyl (DPPH) assay (Fig. 2). All three constituents showed activities
      similar to that of the reference antioxidant alpha-tocopherol (vitamin E).

PMID- 17193185
TI  - Sequence-specific conjugates of oligo(2'-O-methylribonucleotides) and hairpin
      oligocarboxamide minor-groove binders: design, synthesis, and binding studies
      with double-stranded DNA.
AB  - New conjugates of triplex-forming pyrimidine oligo(2'-O-methylribonucleotides)
      with one or two 'head-to-head' hairpin oligo(N-methylpyrrole carboxamide) minor
      groove binders (MGBs) attached to the terminal phosphate of the oligonucleotides
      with a oligo(ethylene glycol) linker were synthesized. It was demonstrated that,
      under appropriate conditions, the conjugates form stable complexes with double
      stranded DNA (dsDNA) similarly to triplex-forming oligo(deoxyribonucleotide)
      (TFO) conjugates containing 5-methylated cytosines. Kinetic and thermodynamic
      parameters of the complex formation were evaluated by gel-shift assay and thermal
      denaturation. Higher melting temperatures (Tm), faster complex formation, and
      lower dissociation constants (Kd) of the triple helices (6-7 nM) were observed
      for complexes of MGB-oligo(2'-O-methylribonucleotide) conjugates with the target
      dsDNA compared to the nonconjugated individual components. Interaction of MGB
      moieties with the HIV proviral DNA fragment was indicated by UV/VIS absorption
      changes at 320 nm in the melting curves. The introduction of thymidine via a
      3',3'-type 'inverted' phosphodiester linkage at the 3'-end of oligo(2'-O
      methylribonucleotide) conjugates (3'-protection) had no strong influence on
      triplex formation, but slightly affected complex stability. At pH 6.0, when one
      or two hairpin MGBs were attached to the oligonucleotide, both triplex formation
      and minor-groove binding played important roles in complex formation. When two
      'head-to-head' oligo(N-methylpyrrole) ligands were attached to the same terminal
      phosphate of the oligonucleotide or the linker, binding was observed at pH >7.5
      and at high temperatures (up to 74 degrees). However, under these conditions,
      binding was retained only by the MGB part of the conjugate.

PMID- 17193187
TI  - X-ray single-crystal analysis of (-)-(S)-equol isolated from rat's feces.
AB  - The biological effects of soy isoflavones have attracted considerable interest in
      recent years, leading to numerous studies on dietary intake and epidemiology. (-)
      (S)-equol (3) is a metabolite produced in vivo from the isoflavone daidzein, a
      kind of soy phytoestrogen, by the action of gut microflora. It has higher
      biological activity than its precursor. Here, we wish to report the isolation and
      first X-ray crystal structure of 3 from the feces of rats fed a soy-isoflavone
      containing diet.

PMID- 17193188
TI  - Inhibition of glycosylation processes: the reaction between pyridoxamine and
      glucose.
AB  - Glycosylation of proteins by glucose produces toxic and immunogenic compounds
      called 'advanced glycosylation end products' (AGEs), which are the origin of
      pathological symptoms in various chronic diseases. In this work, a kinetic study
      of the reaction between glucose (2) and pyridoxamine (1)--a potent inhibitor of
      AGEs formation both in vivo and in vitro--was conducted. The NH2 group of
      pyridoxamine was found to react with the C=O group of glucose to form the Schiff
      base 9 (Scheme 2). Subsequently, the Schiff base gives rise to other products,
      including compound 3, pyridoxal, pyridoxine, and 4-pyridoxic acid. Compound 3
      inhibits the Amadori rearrangement, and prevents the formation of other C=O
      groups capable of triggering glycosylation processes. Pyridoxal and pyridoxine
      can also inhibit protein glycosylation via other previously reported mechanisms.

PMID- 17193189
TI  - Nucleolipids: natural occurrence, synthesis, molecular recognition, and
      supramolecular assemblies as potential precursors of life and bioorganic
      materials.
AB  - Nucleolipids are hybrid molecules composed of a nucleobase, a nucleoside, a
      nucleotide or an oligonucleotide (either DNA or RNA), and a lipophilic moiety,
      which might be either simply a single- or double-chained alkyl (or alkenyl)
      moiety or a carbocyclic hydrocarbon such as cholesterol, a vitamin, or a bile
      acid. This review covers all aspects of nucleolipids, namely their natural
      occurrence, their synthesis, their molecular recognition, as well as aggregation
      behavior, either in aqueous or non-aqueous solution. Potential future aspects of
      nucleolipids in material sciences and for the elucidation of biochemical
      reactions in living cells are discussed.

PMID- 17193190
TI  - Efficient sialylation on azidododecyl lactosides by using B16 melanoma cells.
AB  - Lactoside primers (dodecyl lactoside derivatives) resemble intermediates in the
      biosynthetic pathway of glycolipids and, therefore, act as substrates for
      cellular enzyme-catalyzed glycosylation. To establish the optimal condition for
      the bioproduction of a large amount of valuable materials containing GM3-type
      oligosaccharides, two kinds of lactoside primers having the azido group in
      different positions were synthesized and introduced into B16 melanoma cells. The
      saccharide chains of both primers were elongated by cells to give GM3-type
      oligosaccharide derivatives, which were released to the culture medium. The
      amount of glycosylated product from newly synthesized 2-azidododecyl beta
      lactoside (primer II) was almost twice that from 12-azidododecyl beta-lactoside
      (primer I). The effects of seeded cell number, primer concentration, and length
      of incubation time on the glycosylation efficiency were also investigated. The
      results showed that the higher the seeded cell number, the larger the amount of
      sialylated products obtained. The optimum concentrations of primers I and II were
      found to be 200 and 100 microM, respectively. Above these concentrations,
      productivity and cell viability decreased. As regards the length of incubation
      time, the sialylated products increased linearly until 48 h, but productivity did
      not advance thereafter. These results represent the optimal conditions that are
      necessary for the mass production of GM3-type oligosaccharide using azidododecyl
      lactoside primers and B16 cells.

PMID- 17193191
TI  - The Isiokpo oil-pipeline leakage: total organic carbon/organic matter contents of
      affected soils.
AB  - The environmental impact of the 1997 leakage of the high-pressure crude-oil
      pipeline at Isiokpo in the Niger Delta in the southeast of Nigeria was evaluated,
      with particular reference to total-organic-carbon (TOC) and total-organic-matter
      (TOM) contents of soils within the vicinity of the oil spillage. The soils, taken
      from depths of 0-15 cm (surface) and 15-30 cm (subsurface), were found to be more
      acidic (pH 4.2-5.6) than the unpolluted soils, with a high average moisture
      content of 6.8%. The extractable hydrocarbon content ranged from 2.71-3.48 mg/kg,
      indicating hydrocarbon contamination. However, contrary to expectation, the TOC
      and TOM contents of the polluted soils did not show any significant increase in
      concentration, supposedly due to natural rehabilitation of the affected mat layer
      of soils. Thus, notwithstanding the possible proliferation of heterotrophic
      organisms by the presence of the added petroleum hydrocarbons, environmental
      conditions such as weathering and climatic predispositions, as well as physico
      chemical parameters such as pH, moisture content, and temperature must have
      encumbered the carbon-mineralizing capacity of the heterotrophs, thereby reducing
      the turnover of carbon and the decomposition of organic matter. The restrictions
      by high moisture content might not come directly from H(2)O itself, but are
      probably a consequence of hindered soil ventilation, which reduces O(2) supply
      and gaseous diffusion, conditions that might have been substantially aggravated
      by the added petroleum hydrocarbons.

PMID- 17193192
TI  - Molecular-dynamics simulations of C- and N-terminal peptide derivatives of GCN4
      p1 in aqueous solution.
AB  - We report the investigation of two 16-residue peptides in aqueous solution by
      means of molecular-dynamics simulations. The peptides constitute the C- and N
      terminal halves of the 33-residue monomer whose dimer constitutes the leucine
      zipper of the yeast transcriptional activator, denoted GCN4-p1. To examine a
      hypothesis about coiled-coil formation, in which the C-terminal half contains a
      helix-formation trigger site absent in the N-terminal half, experimental studies
      of the two peptides have determined their helix propensities under several
      conditions of temperature, pH, and salt concentration with circular dichroism. An
      NMR experiment provides additional evidence. At temperatures of 278 and 325 K and
      pH 7.5, mixtures of alpha- and pi-helical secondary structure constitute the most
      probable conformations in both C- and N-terminal halves. A bifurcated salt bridge
      between Arg25 and Glu22/20 correlates with the structural fluctuations of the C
      terminal half. It also exhibits a persistent loop at the N-terminal end involving
      the side chains of His18 and Glu22, which is reminiscent of helix-capping boxes.
      Nonreversible unfolding appears to occur abruptly in the Arg25 mutant, suggesting
      a cooperative event. Analysis does not indicate that the N-terminal half is less
      stable than the C-terminal half, indicating that 100 ns is too short a period to
      observe complete unfolding.

PMID- 17193193
TI  - Drimanes and other terpenoids from the fern Thelypteris hispidula (Decne.) Reed.
AB  - The drimane-type sesquiterpenoids (-)-polygodial (1), (-)-isopolygodial (4),
      drimenin (5), and isodrimenin (6) were isolated from a pungent Argentine
      collection of the fern Thelypteris hispidula, along with other terpenoids. As the
      mentioned drimanes have been previously found in liverworts, the present results
      strongly support the theory that Pteridophytes and Bryophytes share the same line
      of evolution. Our present investigations indicate that two chemotypes of T.
      hispidula are widespread in the northwest of Argentina. Plants belonging to the
      pungent chemotype contain drimanes, while nonpungent plants lack drimanes.

PMID- 17193194
TI  - Biotechnological production and bioactivities of mollisin and two new,
      structurally related fungal naphthoquinone metabolites.
AB  - The antibiotic and fungicidal deuteromycete Mollisia caesia Sacc. was cultivated
      on a large scale. Mollisin (1; = 8-(dichloroacetyl)-5-hydroxy-2,7
      dimethylnaphthalene-1,4-dione) and two new tri- and tetrahalogenated metabolites,
      mollisin A (2) and mollisin B (3) were isolated from M. caesia. The formation of
      2 and 3 indicates that the biosynthesis of these compounds starts from a C(16)
      polyketide (Scheme). Mollisin (1) shows strong fungicidal activities against
      Sclerophoma pityophila (Corda) v. Hohn and Heterobasidion annosum (Fr.) Bref.,
      which is one of the most-destructive basidiomycetes in coniferous forests. The
      metabolites 1-3 possess interesting pharmacological activities in assays in
      search of anti-inflammatory and antiproliferative drugs.

PMID- 17193195
TI  - Polyazacyclophanes incorporating two pyridine units and a heteroaromatic pendant
      group as potential cleaving agents of mRNA 5'-cap structure.
AB  - Four hexaazacyclophanes, 16a-d, incorporating two pyridine units and a (pyridin-2
      yl)methyl or (quinolin-2-yl)methyl pendant group at one of the ring N-atoms have
      been prepared. The key step of the synthesis is an intermolecular cyclization of
      N,N-bis{[6-(tosyloxymethyl)pyridin-2-yl]methyl}-2-nitrobenzenesulfonamide (7)
      with either tert-butyl bis{2-[(2-nitrophenylsulfonyl)amino]ethyl}carbamate (2a)
      or tert-butyl bis{3-[(2-nitrophenylsulfonyl)amino]propyl}carbamate (2b) in the
      presence of anhydrous Cs(2)CO(3). Removal of the acid-labile tert-butoxycarbonyl
      protection then allows attachment of the pendant group by reductive alkylation to
      the exposed secondary amino group, and deprotection of the remaining aliphatic
      ring N-atoms completes the synthesis. The ability of the cyclophanes and their
      dinuclear Cu(2+) and Zn(2+) complexes to cleave the mRNA cap structure,
      m(7)G(5')pppG(5') (1), has been studied.

PMID- 17193196
TI  - The first total synthesis of the peptaibol hypomurocin A1 and its conformation
      analysis: an application of the 'azirine/oxazolone method'.
AB  - The first total synthesis of Hypomurocin A1 (HM A1) in solution phase is
      described. As members of the peptaibol family, hypomurocins are constituted by
      two groups of peptides: six undecapeptides (undecamers) in the HM A group and six
      octadecapeptides (18-mers) in the HM B group. The synthesis presented has been
      successfully achieved by the 'azirine/oxazolone method' to introduce the two Aib
      Pro sequences included in this undecapeptaibol in one step with methyl 2,2
      dimethyl-2H-azirine-3-prolinate as the building block. The coupling reactions of
      the Z-protected amino acids or peptide acids involved the use of N,N,N',N'
      tetramethyluronium tetrafluoroborate (TBTU) and 1-hydroxybenzotriazole (HOBt),
      and led to the peptides in good-to-very-good yields. The peptides were purified
      by reverse-phase HPLC and characterized by NMR spectroscopy (1H, 13C, COSY,
      TOCSY, HSQC, HMBC, ROESY), ESI-MS, IR, elemental analysis, optical rotation, and
      X-ray crystallography. An NMR analysis of HM A1 was also carried out in
      deuterated micelles to perform a structural comparison of the helix in solution
      and in membranes.

PMID- 17193198
TI  - Antileishmanial physalins from Physalis minima.
AB  - Three new physalins (1-3) and a new withanolide 7 have been isolated from the
      whole plant of Physalis minima, along with three known physalins: physalin H (4),
      isophysalin B (5), and 5beta,6beta-epoxyphysalin B (6). Their structures were
      deduced on the basis of in-depth spectroscopic analyses. Compounds 1-6 showed
      significant in vitro leishmanicidal activities (0.92-19.4 microg/ml) against
      promastigotes of Leishmania major.

PMID- 17193199
TI  - Compositional diversity of terpenoids in the Himalayan Valeriana genera.
AB  - In an effort to determine the chemical diversity of the Valeriana genera of the
      Northwestern Himalaya (Uttaranchal), V. wallichii, V. himalayana (syn. V.
      dioica), V. pyrolaefolia, and V. hardwickii var. arnottiana were investigated for
      their terpenoid compositions by means of GC and GC/MS analyses of their essential
      oils, as well as by one- and two-dimensional NMR studies of the isolates. Our
      results establish that V. wallichii DC. includes two stable chemotypes, with no
      mixed population, chemotype I being characterized by the presence of maaliol (1),
      and chemotype II having patchouli alcohol (2) and 8-acetoxypatchouli alcohol (3)
      as major compounds. V. hardwickii var. arnottiana was also found to exist as two
      independent chemotypes. Here, chemotype I is characterized by alpha-kessyl
      acetate (4), valeracetate (5), and 8-epikessyl glycol diacetate (6), whereas the
      chemotype-II species contain maaliol (1) and kessanyl acetate (7). V. himalayana
      Grub. had maaliol (1), valeranone (8), kessane (9), and alpha-kessyl acetate (4)
      as major compounds, and V. pyrolaefolia Decne. contained patchouli alcohol (2)
      and valeranone (8) as markers.

PMID- 17193197
TI  - Synthesis of RNA containing O-beta-D-ribofuranosyl-(1''-2')-adenosine-5''
      phosphate and 1-methyladenosine, minor components of tRNA.
AB  - tRNA is best known for its function as amino acid carrier in the translation
      process, using the anticodon loop in the recognition process with mRNA. However,
      the impact of tRNA on cell function is much wider, and mutations in tRNA can lead
      to a broad range of diseases. Although the cloverleaf structure of tRNA is well
      known based on X-ray-diffraction studies, little is known about the dynamics of
      this fold, the way structural dynamics of tRNA is influenced by the modified
      nucleotides present in tRNA, and their influence on the recognition of tRNA by
      synthetases, ribosomes, and other biomolecules. One of the reasons for this is
      the lack of good synthetic methods to incorporate modified nucleotides in tRNA so
      that larger amounts become available for NMR studies. Except of 2'-O-methylated
      nucleosides, only one other sugar-modified nucleoside is present in tRNA, i.e.,
      2'-O-beta-D-ribofuranosyl nucleosides. The T loop of tRNA often contains charged
      modified nucleosides, of which 1-methyladenosine and phosphorylated disaccharide
      nucleosides are striking examples. A protecting-group strategy was developed to
      introduce 1-methyladenosine and 5''-O-phosphorylated 2'-O-(beta-D-ribofuranosyl)
      beta-D-ribofuranosyladenine in the same RNA fragment. The phosphorylation of the
      disaccharide nucleoside was performed after the assembly of the RNA on solid
      support. The modified RNA was characterized by mass-spectrometry analysis from
      the RNase T1 digestion fragments. The successful synthesis of this T loop of the
      tRNA of Schizosaccharomyces pombe initiator tRNA(Met) will be followed by its
      structural analysis by NMR and by studies on the influence of these modified
      nucleotides on dynamic interactions within the complete tRNA.

PMID- 17193200
TI  - Enzymatic resolution and odor description of both enantiomers of lavandulol, a
      fragrance of lavender oil.
AB  - Both enantiomers of lavandulol (1), an important constituent of lavender oil,
      were prepared by enzymatic optical resolution, and the odor quality of the single
      antipodes were evaluated. The fragrance of the nature-identical (R)-enantiomer
      ('weak floral, herbal odor with slightly lemon-like, fresh citrus fruity nuance')
      was superior to those of both the unnatural (S)-enantiomer ('very weak odor') and
      the racemate ('weak floral, herbal odor').

PMID- 17193201
TI  - Inhibitors of phenylalanine ammonia-lyase (PAL): synthesis and biological
      evaluation of 5-substituted 2-aminoindane-2-phosphonic acids.
AB  - A series of 5-substituted derivatives of the potent phenylalanine ammonia-lyase
      (PAL) inhibitor 2-aminoindane-2-phosphonic acid (AIP; 2) were synthesized. The
      AIP analogues 3-7, with additional NO2, NH2, Me, Br, and OH groups, respectively,
      were tested as in vitro inhibitors of buckwheat PAL, and as in vivo inhibitors of
      anthocyanin biosynthesis. Within this series, the racemic 5-bromo (6) and 5
      methyl (7) congeners were biologically most active (Table), although being ca.
      one order of magnitude less potent than AIP proper.

PMID- 17193202
TI  - 'Green' synthesis of nitro alcohols catalyzed by solid-supported tributylammonium
      chloride in aqueous medium.
AB  - A series of 1-aryl-2-nitroalkan-1-ols (5a-m; Table 2) was prepared in yields of
      64-94% by Henry reaction between aromatic aldehydes and nitroalkanes in the
      presence of a dual catalytic system of KOH and polystyrene-supported
      tributylammonium chloride (PsTBAC; 2). The reactions were performed either in H2O
      containing 10% of THF or, in the case of liquid reagents (aldehydes and
      nitroalkanes), in neat H2O at room temperature. The immobilized phase-transfer
      catalyst, designed to be used for large-scale industrial processes, could be
      easily separated from the products, and effectively re-used several times,
      basically without loss in activity.

PMID- 17193203
TI  - Two novel trimeric resveratrol derivatives from Cotylelobium lanceolatum.
AB  - Two new resveratrol (= 5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol)
      trimers, cotylelophenols A (1) and B (2), were isolated from the stem of
      Cotylelobium lanceolatum (Dipterocarpaceae), together with ten known resveratrol
      oligomers (3-12). The structures of the isolates were established on the basis of
      spectroscopic analyses, including a detailed NMR spectroscopic investigation of 1
      under different conditions. Compound 1 is the first resveratrol trimer with a
      rearranged 4-hydroxyphenyl group. Four possible biogenetic pathways towards
      resveratrol oligomers are proposed (Scheme).

PMID- 17193204
TI  - Synthesis and biological evaluation of novel compounds related to 1
      arylnaphthalene lignans and isoquinolines.
AB  - Novel compounds designed as hybrids of 1-arylnaphthalene lignans with
      isoquinoline alkaloids were prepared and evaluated for their cytotoxicities on
      human tumor cell lines, such as A549, Hela, PC-3, CNE, BEL-7404, and KB. Some of
      the synthetic compounds exhibited their IC50 values on selected cell lines at 10(
      6) M scale. The preliminary CoMFA molecular-modelling studies of these synthetic
      analogues were also performed.

PMID- 17193205
TI  - Preparation and supramolecular properties of unadulterated glycosyl liposomes
      from a bis(alpha-D-mannopyranosyl)-[60]fullerene conjugate.
AB  - The bis(alpha-D-mannopyranosyl)-[60]fullerene conjugate 3 was prepared by thermal
      coupling of C60 and either 2-azidoethyl 2,3,4,6-tetra-O-acetyl- or 2,3;4,6-di-O
      isopropylidene-alpha-D-mannopyranoside (Scheme). Compound 3 was found to readily
      self-assemble. Dynamic-light-scattering (DLS) and atomic-force microscopy (AFM)
      experiments supported that the amphiphilic compound gives rise to nano-sized
      supramolecular structures during sugar deprotection (Ac-group removal) performed
      in MeOH/CH2Cl2 solution. Encapsulation studies with an aqueous suspension of 3
      showed that the self-assembling structure envelopes Ba2+ and the fluorescent dye
      Acridine Red during its formation, which indicates that it resembles a bilayer
      vesicle or an unadulterated liposome with an inner hollow space. In addition to
      this notable property, the unique molecular geometry of the spatially arranged
      mannosyl surface residues of 3 gives rise to strong binding of the carbohydrate
      recognizing lectin Con A. Hence, the polar amphiphilic end of 3 mimics the
      structure of 3,6-branched tri-alpha-D-mannoside (6; Fig. 3), a natural ligand of
      the Con A protein.

PMID- 17193206
TI  - Contribution of oxidative-reductive reactions to high-molecular-weight hyaluronan
      catabolism.
AB  - Since the content of hyaluronan (HA)-degrading enzymes in synovial fluid (SF), if
      any, is extremely low, the high rate of HA turnover in SF is to result from a
      cause different from enzymatic catabolism. An alternative and plausible mechanism
      is that of oxidative-reductive degradation of HA chains by a combined action of
      oxygen and transition metal cations maintained in a reduced oxidation state by
      ascorbate.

PMID- 17193207
TI  - Biosorption of Pb2+ from aqueous solution by waste biomass of aerial roots of
      Rhizophora mangle (red mangrove).
AB  - The processing waste of the aerial roots of Rhizophora mangle was used in both
      its unmodified or mercaptoacetic acid (MAA) modified form for the sorption of
      Pb2+ from aqueous solution. The biomass rapidly and strongly sorbed Pb2+ at pH
      5.0, which indicated chemisorption. A significant increase in Pb2+ sorption
      resulted from MAA treatment of the biomass, indicating that sorption occurs
      through an ion-exchange process. From sorption-capacity experiments, the
      unmodified and modified materials extracted, at pH 5, 31.3 and 85.5 mg of Pb2+
      per gram of biomass, respectively, from aqueous solutions. Our studies may
      contribute to an innovative method for the economical and ecologically save
      removal and recovery of heavy-atom metal ions from contaminated waters through
      biosorption.

PMID- 17193208
TI  - Enantioselective synthesis and cytotoxic evaluation of 4,5-dihydro-5
      [aryl(hydroxy)methyl]-3-methylidenefuran-2(3H)-ones.
AB  - A series of enantiomerically enriched 4,5-dihydro-5-[aryl(hydroxy)methyl]-3
      methylidenefuran-2(3H)-ones (8) were synthesized by means of asymmetric Sharpless
      dihydroxylation of the 2-phosphorylated 5-aryl-pent-4-enoic acids 13, followed by
      Horner-Wadsworth-Emmons reaction of the resulting furanones 15 (Scheme 2). An
      enantiomeric excess (ee) of 20-95% was achieved for compounds 8, and their
      absolute configurations were determined by the Mosher ester method. Cytotoxic
      evaluation against L-1210 and HL-60 leukemia cell lines revealed that the target
      compounds 8 are active in the micromolar concentration range (Table 2). Thereby,
      significant differences in activity between the corresponding enantiomers were
      observed for the HL-60 cell line.

PMID- 17193209
TI  - Adsorption of transition metals in aqueous solutions by fluted pumpkin (Telfairia
      occidentalis Hook f) waste.
AB  - The adsorption of some divalent transition metal (Hg, Rh, Pt, and Pd) ions in
      aqueous solution onto fluted pumpkin waste biomass has been investigated. The
      data were discussed in terms of ionic radii, surface area, and the hard-soft acid
      base (HSAB) concept. The monolayer sorption capacities as obtained by the
      Langmuir adsorption isotherm model were determined to be ca. 9.89 mg/g, 9.81
      mg/g, 10.59 mg/g, and 6.84 mg/g for for Hg(II), Rh(II), Pt(II), and Pd(II),
      respectively. The results are relevant for the optimal design of a wastewater
      treatment plant and for prediction of model parameters of sorbate-sorbent
      interactions.

PMID- 17193210
TI  - A broad diversity of volatile carboxylic acids, released by a bacterial
      aminoacylase from axilla secretions, as candidate molecules for the determination
      of human-body odor type.
AB  - Human body odor is to a large part determined by secretions of glands in the
      axillary regions. Two key odoriferous principles, 3-methylhex-2-enoic acid (3MH2;
      4/5) and 3-hydroxy-3-methylhexanoic acid (HMHA; 6) have been shown to be released
      from glutamine conjugates secreted in the axilla by a specific N(alpha)-acyl
      glutamine aminoacylase (N-AGA) obtained from axilla isolates of Corynebacteria
      sp. However, the low number of different odorants reported in humans stands in
      contrast to the observed high inter-individual variability in body odors. Axilla
      secretions of individual donors were, therefore, analyzed in detail. The
      secretions were treated with N-AGA, analyzed by GC/MS, and compared to undigested
      controls. Over 28 different carboxylic acids were released by this enzyme from
      odorless axilla secretions (Table 1). Many of these body odorants have not been
      reported before from a natural source, and they include several aliphatic 3
      hydroxy acids with 4-Me branches, 3,4-unsaturated, 4-Et-branched aliphatic acids,
      and a variety of degradation products of amino acids. The odor threshold of some
      of the acids was found to be in the range of 1 ng. Most of these compounds were
      present in all donors tested, but in highly variable relative amounts, and they
      are, thus, candidate molecules as key components of a 'compound odor' determining
      the individual types of human body odor.

PMID- 17193211
TI  - Toxicity and synergism in the feeding deterrence of some coumarins on Spodoptera
      frugiperda Smith (Lepidoptera: Noctuidae).
AB  - The phagodepression activity of five coumarins (= 2H-1-benzopyran-2-ones), 6
      hydroxy-7-isoprenyloxycoumarin (1), 6-methoxy-7-isoprenyloxycoumarin (2), 6,7
      methylenedioxycoumarin (3), 5-methoxy-6,7-methylenedioxycoumarin (4), and 6
      methoxy-7-(2-hydroxyethoxy)coumarin (5), from the Argentine native herb
      Pterocaulon polystachyum, was tested against Spodoptera frugiperda (Lepidoptera:
      Noctuidae) larvae. Two analogs, scopoletin (6) and 2-methoxy-2-methyl-3,4,5,6,7,8
      hexahydro-3H-chromen-5-one (7), synthesized in our laboratory, were also
      evaluated for comparison. The compounds were added to an artificial diet at doses
      ranging from 50 to 200 microg per g of diet. Natural coumarins induced 100% of
      phagodepression when 200 microg were added per g of diet. Binary equimolar
      mixtures of the natural coumarins were phagodepressors against S. frugiperda
      surpassing the expected additive responses, indicating that these compounds can
      act synergistically against S. frugiperda larvae. Compounds 1 and 3 (non
      methoxylated coumarins), and the equimolar mixture of both, displayed the
      strongest phagodepression. Additionally, 50 microg/g of 1 and 3 incorporated to
      the larval diet caused 80 and 50% of pupal mortality, respectively, while a 100
      microg/g dose of compounds 2, 4, 6, and 7 produced 60, 50, 10, and 80% pupal
      mortality, respectively. Larval growing rate during the early larval instars was
      significantly reduced by treatments with the methylenedioxycoumarins 3 and 4.
      Coincidentally, the larval period duration was significantly increased by the
      latter compounds.

PMID- 17193212
TI  - Infrared spectroscopy as a tool for chemotaxonomic investigations within the
      Achillea millefolium group.
AB  - An FT-IR-based method for the rapid characterization and identification of
      Achillea species was developed. With the IR spectra of the CH2Cl2 extracts of A.
      aspleniifolia, A. collina, A. millefolium, A. millefolium ssp. sudetica, A.
      pannonica, A. pratensis, A. roseoalba, A. setacea, and A. styriaca, a spectrum
      library was created. This database allowed the identification of the respective
      taxa by comparison of IR spectra. Moreover, information concerning dominant
      structural elements of sesquiterpene constituents was obtained, providing hints
      about the composition of a plant sample of unknown origin.

PMID- 17193213
TI  - Antifungal bis[bibenzyls] from the Chinese liverwort Marchantia polymorpha L.
AB  - Bioassay-guided separation of the antifungal constituents of the Chinese
      liverwort Marchantia polymorpha L. (Marchantiaceae) led to the isolation of seven
      bis[bibenzyl]-type macrocycles. On the basis of NMR and MS analyses, the three
      new compounds plagiochin E (1), 13,13'-O-isoproylidenericcardin D (4), and
      riccardin H (7) were identified, together with four known compounds: marchantin E
      (2), neomarchantin A (3), marchantin A (5), and marchantin B (6). Their
      antifungal activities against Candida albicans were determined by TLC
      bioautography.

PMID- 17193214
TI  - Trichotomoside: a new antioxidative phenylpropanoid glycoside from Clerodendron
      trichotomum.
AB  - The structure and antioxidant properties of a new natural glycoside,
      trichotomoside (1), isolated from Clerodendron trichotomum, were investigated.
      Trichotomoside was identified as 2-(3-hydroxy-4-methoxyphenyl)ethyl 3-O-(2,3-di-O
      acetyl-alpha-L-rhamnopyranosyl)-4-O-[(2E)-3-(3-hydroxy-4-methoxyphenyl)prop-2
      enoyl]-beta-D-glucopyranoside. The compound was active towards intracellular
      reactive oxygen species (ROS) and exhibited DPPH-radical-scavenging effects. The
      radical-scavenging activity of 1 was found to protect the viability of Chinese
      hamster lung fibroblasts (V79-4 cells) exposed to H2O2 and gamma-irradiation.

PMID- 17193215
TI  - Larvicidal activity of bis(2-ethylhexyl) benzene-1,2-dicarboxylate from Sterculia
      guttata seeds against two mosquito species.
AB  - The larvicidal activities of various fractions of the hexane extract of the seeds
      of Sterculia guttata against larvae of Aedes aegypti and Culex quinquefasciatus
      were determined. Bis(2-ethylhexyl) benzene-1,2-dicarboxylate (1) was identified
      as one of the active principles, displaying chronic toxicity against both types
      of larvae, with LD50 values of 79 and 64 ppm, respectively.

PMID- 17193216
TI  - Structure elucidation and antibacterial activity of new fungal metabolites of
      sclareol.
AB  - The transformation of the antibacterial diterpene sclareol (1) by two different
      fungal strains was investigated (Scheme). In the presence of Rhizopus stolonifer,
      (3beta)-3-hydroxysclareol (2), 18-hydroxysclareol (3), (6alpha)-6,18
      dihydroxysclareol (4), and (11S)-11,18-dihydroxysclareol (5) were formed.
      Fermentation of 1 with Fusarium lini afforded (1beta)-1-hydroxysclareol (6) and
      (12S)-12-hydroxysclareol (7). Compounds 4-7 were identified as new compounds, and
      some of them were active against Bacillus subtilis (Table 3).

PMID- 17193217
TI  - A homo-isoflavonoid and a cytotoxic saponin from Dracaena draco.
AB  - Two new compounds, dracol (= (3R)-2,3-dihydro-3,5-dihydroxy-7-methoxy-3-[(4
      methoxyphenyl)methyl]-8-methyl-4H-[1]benzopyran-4-one; 1) and icodeside (=
      (1beta,3beta,23S,24S)-3,23-dihydroxy-1-{[2-O-(2,3,4-tri-O-acetyl-alpha-L
      rhamnopyranosyl)-alpha-L-arabinopyranosyl]oxy}spirosta-5,25(27)-dien-24-yl alpha
      L-arabinopyranoside; 2), were isolated from the EtOH extract of the leaves of
      Dracaena draco, together with 17 known constituents. The structures of 1 and 2
      were elucidated by in-depth spectroscopic analysis, and those of the known
      compounds were identified by comparison of their NMR and MS data with those
      reported in the literature. Icodeside (2) showed moderate cytotoxicity against
      human HL-60 and A-431 cells (Table 3).

PMID- 17193218
TI  - 3 Beta-hydroxyolean-12-en-27-oic acid: a cytotoxic, apoptosis-inducing natural
      drug against COLO-205 cancer cells.
AB  - 3Beta-hydroxyolean-12-en-27-oic acid (1), a biologically active, pentacyclic
      triterpenoid isolated from the rhizomes of Astilbe chinensis, was found to be
      considerably more cytotoxic toward human colorectal carcinoma (COLO-205) and
      human cervical squamous carcinoma (HeLa) cells than its congener oleanolic acid
      (4). This suggests that the position of the COOH group significantly affects the
      cytotoxicity of oleanane-type pentacyclic triterpene carboxylic acids. To
      elucidate the underlying biological mechanism responsible for the cytotoxicity of
      1, we investigated its growth-inhibitory effect on COLO-205 cells. Compound 1
      induced a marked concentration- and time-dependent inhibition of cell
      proliferation, with the typical morphological characteristics of apoptosis, and
      under formation of DNA ladders in agarose-gel electrophoresis. Flow-cytometric
      analysis showed that the cell cycle of COLO-205 cells exposed to 1 was arrested
      in the G0/G1 phase. Also, 1 increased and decreased the expression of Bax and Bcl
      2 proteins, respectively, and lowered the mitochondrial transmembrane potential
      (delta psi(m)). The peptidic caspase-3 inhibitor NH2-Asp-Glu-Val-Asp-CHO (at 1
      microM) could increase the viability of COLO-205 cells previously treated with 1.
      These results indicate that 1 induces efficient cell apoptosis through down
      regulating Bcl-2 expression, up-regulating Bax expression, lowering delta psi(m),
      and by activating the caspase-3 pathway.

PMID- 17193219
TI  - Assessment of heavy-metal profile of the New Calabar River and its impact on
      juvenile Clarias gariepinus.
AB  - We have determined the heavy-metal status of the lower reaches of the New Calabar
      River in the Niger Delta region over a 40-km-long distance, and its impact on the
      development of catfish (juvenile Clarias gariepinus). The total mean
      concentrations of dissolved trace metals in the river were 0.01, 0.85, 0.56,
      2.08, 0.05, 12.0, and 6.59 mg/l for Hg, Pb, Cd, Cu, Cr, Fe, and Zn, respectively.
      The accumulated concentration of trace metals in the muscles of different mature
      fish caught from the river were examined, and the results fell within the action
      levels adopted in most countries. To evaluate the contributions of trace metals
      to fisheries depletion, eggs of C. gariepinus were hatched in dilution water
      spiked with the total mean metal levels determined in the river water. Our
      results indicate substantive inhibition of egg hatch even at very low
      concentrations of the majority of the trace metals studied, with mortality rates
      well above 50% after 216 h of exposure (Table 5). These findings suggest that
      trace metals (except for Zn), even at very low concentrations, negatively affect
      fish hatch and fry rearing, implying that aquatic milieus contaminated by trace
      metals are not suitable as nursery grounds for fish cultures.

PMID- 17193220
TI  - Trace-metal contamination of the African giant land snail Archachatina marginata
      from Southern Nigeria.
AB  - The levels of bio-accumulated trace metals in the African giant land snail
      Archachatina marginata, collected in six different states of Southern Nigeria,
      were determined. The Cu and Fe levels were 3.0-9.8 and 12.4-35.2 mg/kg body
      weight, respectively (Table). Similarly, the concentrations of Zn, Ni, Pb, and Cd
      were 10.3-20.5, 3.20-10.4, 0.80-6.00, and 0.60-0.84 mg/kg, respectively. Although
      the trace-metal levels for some samples collected in highly industrialized zones
      approached or even considerably exceeded the upper WHO limits, the average
      concentrations of trace metals recorded in this study remained below critical
      values.

PMID- 17193221
TI  - From linden flower to linden honey. Part 2: Glycosidic precursors of cyclohexa
      1,3-diene-1-carboxylic acids.
AB  - The presence of two unusual, recently identified terpene acids, i.e., 4-(1
      hydroxy-1-methylethyl)cyclohexa-1,3-diene-1-carboxylic acid (1) and 4-(1
      methylethenyl)cyclohexa-1,3-diene-1-carboxylic acid (2), was now also confirmed
      in (Swiss) linden honey, after solid-phase extraction and HPLC purification. NMR
      Spectroscopy, in combination with UPLC/MS analysis, showed the presence of
      several glycosides of 1, which accounted for ca. 0.6 weight-% of the honey, as
      quantified by UPLC-UV. The major 'glycoside' of 1, compound 5, could be isolated
      and identified by 2D-NMR experiments as the corresponding beta-gentiobiosyl ester
      (rather than the classical compound with a glycosidic bond between an aglycone OH
      group and the sugar). The same diglycosides found in linden honey were also
      detected in linden nectar; also, chestnut and fir honeys contained these
      glycosides in minor quantities, but not colza, acacia, or dandelion honeys (Table
      2).

PMID- 17193222
TI  - A pair of novel cytotoxic polyprenylated xanthone epimers from gamboges.
AB  - Two new polyprenylated xanthone epimers were isolated from gamboges of Garcinia
      hanburyi, and identified by detailed spectroscopic analysis as 30-hydroxygambogic
      acid (2a) and its (2S)-epimer 30-hydroxyepigambogic acid (2b). Both compounds
      exhibited significant cytotoxicities against the human leukemia K562/S and the
      corresponding doxorubicin-resistant K562/R cell lines (Table 2).

PMID- 17193223
TI  - Synthesis and biological evaluation of new quinazoline and cinnoline derivatives
      as potential atypical antipsychotics.
AB  - Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained
      aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized
      (Schemes 2 and 3), and evaluated for their binding affinities (Table) towards the
      serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new
      compounds, the quinazoline derivative 15 (= 7-{[4-(4-fluorobenzoyl)piperidin-1
      yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities
      towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the
      borderline of potential atypical antipsychotics. The cinnoline derivative 23 (= 7
      {[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5
      one) displayed high selectivity in its binding profile towards the 5-HT2C
      compared to both the 5-HT2A and D2 receptors.

PMID- 17193224
TI  - The biochemistry of drug metabolism--an introduction: part 1. Principles and
      overview.

PMID- 17193225
TI  - Thermotropic lipid phase transition and the behavior of hydrolytic enzymes in the
      kidney cortex brush border membrane.
AB  - Functional interactions of lipids and proteins were examined in brush-border
      membranes isolated from the kidney cortex by studying the temperature dependence
      of the hydrolytic enzyme activities. A close relationship was observed for the
      membrane proteins and the thermotropic lipid phase transitions. Three lines of
      evidences were provided for such dependence: a) Arrhenius relationship of the
      membrane-bound enzyme activities, and the effect of temperature in native and
      partially delipidated membranes, b) differential scanning calorimetric study of
      the membrane lipid phase transitions in the native and delipidated membranes,
      multilamellar vesicles prepared from the membrane extracted lipids, and in
      vesicles from dimyristoyl phosphatidylcholine, and c) the excimer (dimer)
      formation studies of the membrane extrinsic fluorescent probe, pyrene, and the
      resultant membrane microviscosity. The brush-border membranes were partially
      delipidated with BuOH and 2,2,2-trifluoroethanol. The functional interactions of
      the delipidated membranes, which were greatly lost on lipid removal, were largely
      restored by the addition of exogenous lipids in the reconstitution process, which
      indicate the critical dependence of the membrane integral proteins on the
      neighboring lipid molecules in the bulk lipid phase.

PMID- 17193226
TI  - The essential oil of Lippia alba: analysis of samples from French overseas
      departments and review of previous works.
AB  - This paper contains new data on the chemical composition of the essential oil of
      Lippia alba (Mill.) N. E. Brown, as well as an overview of the available
      literature. Although the composition of the essential oil of this species is well
      documented, discrepancies between the reported results suggest that many
      chemotypes and morphotypes exist. The analysis of essential oils obtained from
      the leaves of samples from three different locations in the French Overseas
      Departments (French Guiana, Martinique, and two different places in Guadeloupe)
      have shown that the composition of each one is quite different. This new data,
      along with a review and discussion of published studies, enabled us to establish
      seven distinct chemotypes. Possible connections between these chemotypes and
      morphotypes already described were also investigated.

PMID- 17193227
TI  - Synthesis of 4/5-deoxy-4/5-nucleobase derivatives of 3-O-methyl-D-chiro-inositol
      as potential antiviral agents.
AB  - Using D-pinitol (= 3-O-methyl-D-chiro-inositol) as starting material, a concise
      synthesis of 4/5-deoxy-4/5-nucleobase derivatives 11-19 has been achieved. The
      key intermediate 9 was obtained in good yield via an epoxidation from mono
      methanesulfonate of D-pinitol. The process of opening of the epoxide ring in 9 by
      nucleobases appeared to be regioselective in presence of 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU). All the synthesized carbocyclic nucleosides
      were assayed against several viruses and tumors such as HIV-1, HSV-1, and HSV-2,
      and lung and bladder cancer. However, only compounds 14b, 14a, 16a, 16b, and 19
      showed mild inhibitory effect against human lung cancer cell lines (PG) with IC50
      values ranging from 50 to 100 microM, and the other compounds did not exhibit any
      significant antiviral activity or cytotoxicity even at concentrations up to 200
      microM.

PMID- 17193228
TI  - Antiherpetic flavones from the heartwood of Artocarpus gomezianus.
AB  - The heartwood of Artocarpus gomezianus was investigated for anti-herpetic
      principles. During the course of the separation, a new compound, artogomezianone
      (1), was isolated, along with the known compounds cycloartocarpin (2),
      isocyclomorusin (3), artocarpin (4), norcycloartocarpin (5), norartocarpetin (6),
      and oxyresveratrol (7). Evaluation of these isolates for inhibitory effects
      against herpes simplex virus (HSV) types 1 and 2 was carried out using the
      inactivation method. Compounds 2, 3, 6 and 7 showed moderate activities against
      both types of HSV, while 1, 4 and 5 were basically inactive.

PMID- 17193230
TI  - Two new taxanes from the needles and branches bark of Taxus cuspidata.
AB  - Two new taxanes were isolated from the MeOH extract of the needles and branches
      bark of the Japanese yew, Taxus cuspidata. The structures were established as
      (2alpha,5alpha,7beta,9alpha,10beta,13alpha)-5,10,13,20-tetraacetoxytax-11-ene
      2,7,9-triol (1) and (2alpha,5alpha,9alpha,10beta)-2,9,10-triacetoxy-5-[(beta-D
      glucopyranosyl)oxy]-3,11-cyclotax-11-en-13-one (2) on the basis of in-depth 1D-
      and 2D-NMR analyses. Compound 2 is the first example of a transannular taxane
      glycoside isolated from a natural source.

PMID- 17193229
TI  - Haemolytic activity and adjuvant effect of notoginsenoside K from the roots of
      Panax notoginseng.
AB  - Notoginsenoside K (1), a saponin isolated from the roots of Panax notoginseng
      (Burk.) F. H. Chen, was evaluated for its haemolytic activity and adjuvant
      potential on specific antibody and cellular response to ovalbumin (OVA) in mice.
      Compound 1 showed a slight haemolytic effect, its concentration inducing 50% of
      the maximum haemolysis (HD50 value) being 318+/-13 microg/ml, on a 0.5%
      suspension of red blood cells. Compound 1 significantly increased the
      concanavalin A (Con A)-, lipopolysaccharide (LPS)-, and OVA-induced splenocyte
      proliferation in OVA-immunized mice (P<0.05, P<0.01, or P<0.001). The OVA
      specific serum IgG, IgG1, and IgG2b antibody levels were also significantly
      enhanced by 1, especially at a dose of 25 mug compared to an OVA control group
      (P<0.001). Moreover, the enhancing effect of 1 on the OVA-specific IgG2b antibody
      responses to OVA in mice was more significant than that of Alum (AlOH gel;
      P<0.01). These results suggest that 1 exhibits a slight haemolytic activity and a
      significant adjuvant effect on specific antibody and cellular response against
      OVA in mice.

PMID- 17193231
TI  - Chemical constituents of the plants in the genus Achillea.

PMID- 17193232
TI  - Comparison of permeation through phosphatidylcholine bilayers of N-dipicolinyl
      alpha- and -beta-oligopeptides.
AB  - Cell-membrane permeation of small therapeutic peptides and peptidomimetics is a
      fundamental issue in pharmaceutical research. Using a Tb(3+)-based permeation
      assay, we have examined the ability of alpha- and beta-peptides, bearing
      proteinogenic side chains and an N-terminal dipicolinic acid (DPA) monoamide
      group, to enter liposomes composed of egg phosphatidylcholine bilayers. A series
      of 12 DPA-peptides of increasing chain length was prepared and characterized by
      CD and NMR analysis. An interesting destabilizing effect of the N-terminal DPA
      group on the helical structure of a beta-hexapeptide was discovered. Significant
      differences in permeation were observed between the DPA-alpha- and the DPA-beta
      peptides, with all beta-peptidic compounds permeating better than their alpha
      analogs. Thus, beta-peptides have been shown to interact with lipid bilayers in a
      manner that is distinctly different from that of alpha-peptides. Together with
      the fact that beta-peptides are proteolytically stable in mammalian organisms,
      and that they fold to form helices and hairpin turns with short chain lengths,
      the new results further emphasize the biomedical potential of beta-peptides.

PMID- 17193233
TI  - The production of de novo folded proteins by a stepwise chain elongation: a model
      for prebiotic chemical evolution of macromolecular sequences.
AB  - We describe an experimental procedure to mimic the formation of long (over 40
      residues) co-oligopetide sequences in many identical copies which may have
      occurred in the prebiotic molecular evolution. The basic hypothesis is that chain
      formation is based on the stepwise fragment condensation of randomly generated
      short oligopeptides, whereby the elongation takes place under the contingent
      environmental constraints (solubility, pH, salinity), which eliminate most of the
      products, and thus determine the selection towards one particular small set of
      chains. The present work aims at verifying the validity of this scheme. In order
      to do so, we utilize a classic synthetic procedure based on the Merrifield solid
      phase synthesis of peptides for the synthesis of randomly produced peptides as
      well as for their stepwise fragment condensation. Thus, starting from a library
      of peptides with n=10, the first condensation step produces a library of 16
      peptides with 20 residues each (n=20), of which only four remain water-soluble
      and, therefore, capable to undergo the next fragment condensation step. This
      gives rise to 16 peptides with n=30, out of which twelve precipitate out under
      the chosen pH and buffer conditions and are eliminated. Finally, a 44-residue
      long water-soluble de novo protein is obtained. This has no homologies or
      similarities with extant proteins, and, based on circular dichroism (CD), it
      assumes a stable three-dimensional folding. In agreement with CD data, molecular
      modelling simulations suggest an helical fold for the protein with poor, if any,
      structural homology with known proteins. The implication of this procedure as a
      general mechanism for the etiology of de novo macromolecular sequences and
      globular proteins in the origin of life is briefly discussed.

PMID- 17193234
TI  - Five new steroidal compounds from Ypsilandra thibetica.
AB  - Five new steroids, including the four new steroidal saponins ypsilandroside B
      (1), ypsilandroside A (2), isoypsilandroside A (4), and isoypsilandroside B (5),
      as well as the new steroidal sapogenin isoypsilandrogenin (3), were isolated from
      the whole plant of Ypsilandra thibetica Franch. Their structures were determined
      on the basis of spectroscopic analyses, including extensive 2D-NMR techniques.
      The structure and relative configuration of ypsilandroside B
      (=(3beta,12alpha,25R)-3-[(alpha-L-rhamnopyranosyl-(1-->2)-beta-D
      apiofuranosyl)oxy]spirost-5-ene-12,27-diol; 1) was unequivocally determined by
      single-crystal X-ray diffraction. The antifungal and antibacterial activities of
      1-5 towards various types of fungi and bacteria are reported.

PMID- 17193235
TI  - DNA-binding studies of mixed-ligand (ethylenediamine)ruthenium(II) complexes.
AB  - A series of mixed-ligand ruthenium(II) complexes of the type [Ru(en)(2)bpy](2+)
      (bpy=2,2-bipyridine; 1), [Ru(en)(2)phen](2+) (phen=1,10-phenantroline; 2),
      [Ru(en)(2)IP](2+) (IP=imidazo[4,5-f][1,10]phenanthroline; 3), and
      [Ru(en)(2)PIP](2+) (PIP=2-phenylimidazo[4,5-f][1,10]phenanthroline; 4) have been
      isolated and characterized by UV/VIS, IR, and (1)H-NMR spectral methods. The
      binding of the complexes with calf thymus DNA has been investigated by
      absorption, emission spectroscopy, viscosity measurements, DNA melting, and DNA
      photo-cleavage. The spectroscopic studies together with viscosity measurements
      and DNA melting studies support that complexes 1 and 2 bind to CT DNA (=calf
      thymus DNA) by groove mode. Complex 2 binds more avidly to CT DNA than complex 1,
      complexes 3 and 4 bind to CT DNA by intercalation mode, 4 binds more avidly to CT
      DNA than 3. Noticeably, the four complexes have been found to be efficient
      photosensitisers for strand scissions in plasmid DNA.

PMID- 17193236
TI  - Antituberculotic and antiprotozoal activities of primin, a natural benzoquinone:
      in vitro and in vivo studies.
AB  - Primin (=2-methoxy-6-pentylcyclohexa-2,5-diene-1,4-dione), a natural benzoquinone
      synthesized in our laboratory, was investigated for its in vitro antiprotozoal,
      antimycobacterial, and cytotoxic potential. Primin showed very potent activity
      against Trypanosoma brucei rhodesiense (IC50 0.144 microM) and Leishmania
      donovani (IC50 0.711 microM), and revealed low cytotoxicity (IC50 15.4 microM) on
      mammalian cells. Only moderate inhibitory activity was observed against
      Mycobacterium tuberculosis, Trypanosoma cruzi, and Plasmodium falciparum. When
      tested for in vivo efficacy in a Trypanosoma b. brucei rodent model, primin
      failed to cure the infection at 20 mg/kg given intraperitoneally. Primin was too
      toxic in vivo at a higher concentration (30 mg/kg, injected i.p. route) in mice
      infected with L. donovani. Taken together, primin can serve as a lead compound
      for the rational design of more potent and less toxic antiprotozoal agents.

PMID- 17193237
TI  - Synthesis and pharmacological evaluation of some dual-acting amino-alcohol ester
      derivatives of flurbiprofen and 2-[1,1'-biphenyl-4-yl]acetic acid: a potential
      approach to reduce local gastrointestinal toxicity.
AB  - The search for safer non-steroidal anti-inflammatory drugs (NSAIDs) continues
      with the failure of anticipated 'ideal' anti-inflammatory agents, the coxibs, on
      long-term usage. Increased gastric motility and acidity due to the free carboxy
      group are involved in the etiology of gastric toxicity, common to conventional
      NSAIDs. Keeping this fact in mind, it was planned to modify some of the
      conventional NSAIDs to amino-alcohol ester derivatives, which satisfied the
      structural requirements for these compounds to possess anticholinergic activity
      in the intact form. Besides blocking the acidic carboxylic group, incorporation
      of anticholinergic acivity in these molecules was expected to reduce the gastric
      toxicity by decreasing gastric acid secretion and motility. Synthesis and
      pharmacological evaluation of six different N,N-disubstituted amino-ethyl ester
      derivatives, structurally resembling the amino-alcohol ester class of
      anticholinergic agents, each for [1,1'-biphenyl]-4-acetic acid (3) and
      flurbiprofen (10), have been reported as potential substitutes for these NSAIDs,
      with improved therapeutic profile. All the ester derivatives were found to have
      sufficient chemical stability in buffers (pH 2.0 and 7.4), ensuring them to be
      absorbed as intact moieties from the gastrointestinal tract. A significant
      reduction in ulcerogenic potency in comparison to the parent drugs with a
      slightly higher anti-inflammatory potency suggests that the majority of these
      candidates have an improved therapeutic profile over their parent drugs. Hence, a
      promising novel approach, different from the conventional prodrug concept, has
      been successfully worked out to overcome the local gastric toxicity, yielding
      therapeutically better compounds for long-term oral anti-inflammatory therapy.

PMID- 17193238
TI  - Structure and cytotoxicity of a new lanostane-type triterpene glycoside from the
      sea cucumber Holothuria hilla.
AB  - A new triterpene glycoside, hillaside C (1), was isolated from the sea cucumber
      Holothuria hilla Lesson, which is found in the South China Sea, and its structure
      has been elucidated by spectral analysis (ESI-MS and NMR) and chemical
      transformations. Four known compounds, holothuria A, thymine, uracil, and
      cholesterol, were also obtained. Compound 1 exhibited significant cytotoxicity
      against eight human tumor cell lines (A-549, MCF-7, IA9, CAKI-1, PC-3, KB, KB
      VIN, and HCT-8) with IC50 values in the range of 0.15-3.20 microg/ml.

PMID- 17193239
TI  - A zwitterionic alkaloid, containing a rare cyclopentadienyl anion unit, from the
      stem barks of Daphniphyllum macropodum Miq.
AB  - A new Daphniphyllum alkaloid daphnicyclidin L (1), containing a rare
      cyclopentadienyl anion, which is stabilized as a zwitterion by an internal
      iminium counterion, was isolated from the stem barks of Daphniphyllum macropodum
      Miq., together with four known alkaloids: daphnicyclidin D (2), daphnicyclidin H
      (3), deoxyyuzurimine (4), and yuzurimine (5). The structures were elucidated on
      the basis of spectroscopic data. The configuration of 1 was elucidated by single
      crystal X-ray diffraction crystallography.

PMID- 17193240
TI  - Cassane diterpene-lactones from the seed of Caesalpinia minax HANCE.
AB  - Five new neocaesalpins, named neocaesalpin J-N (1-5, resp.), along with the known
      neocaesalpin A and eight known furanditerpenoids, namely epsilon-caesalpin, 7
      acetoxy-epsilon-caesalpin, 14-deoxy-epsilon-caesalpin, caesalmins D-F, and
      bonducellins C and D, were isolated from the seeds of Caesalpinia minax HANCE.
      Their structures were determined on the basis of spectroscopic analyses.

PMID- 17193241
TI  - Aggregation of cyclodextrins as an important factor to determine their
      complexation behavior.
AB  - Here, we report a study on the complexation behavior of carotenoids with
      cyclodextrins (CDs) using solubility experiments and molecular-modelling methods.
      Carotenoids are an important group of naturally occurring dyes found in
      vegetables and fruits. Their antioxidant property has initiated investigations on
      their possible use as drugs. However, carotenoids are lipophilic molecules with
      very little inherent aqueous solubility. Cyclodextrin complexation has been
      widely used in order to increase the potential applications of hydrophobic
      compounds. Thus, the aim of our investigation was to design carotenoids with
      enhanced water solubility by cyclodextrin complexation. Molecular modelling of
      carotenoid-cyclodextrin complexes with a 1 : 1 stoichiometry successfully
      explained the experimentally observed capability of beta-cyclodextrins (beta-CDs)
      to form complexes with carotenoids as opposed to alpha-cyclodextrins (alpha-CDs)
      and gamma-cyclodextrins (gamma-CDs). Furthermore, molecular-dynamics calculations
      revealed that the aggregation properties of CD derivatives significantly
      influence their complexation behavior. Our docking calculations showed that RAMEB
      (random methylated beta-CD) is the beta-CD derivative that possesses the lowest
      tendency to aggregate. Solubility experiments yielded the same results, namely,
      RAMEB complexes possess the best water solubility. Our results showed that
      complexation of a ligand not buried inside of the CD cavity is dependent on two
      factors: i) the geometry of the inclusion part of the complex; ii) the self
      aggregation property of the CD itself. The lower affinity the CDs possess for
      self-aggregation, the more likely are they involved in interactions with
      carotenoids. These results suggest that self-aggregation of CDs should be
      considered as an important parameter determining complexation in general.

PMID- 17193242
TI  - Nitrilase and its application as a 'green' catalyst.
AB  - Hydrolase-catalyzed reactions have been widely applied in organic synthesis.
      Nitrilases are an important class of hydrolase that converts naturally occurring,
      as well as xenobiotically derived, nitriles to the corresponding carboxylic acids
      and ammonia. Because of their inherent enantio- and regioselectivities and other
      benefits, nitrilases are attractive as 'green', mild, and selective catalysts for
      setting stereogenic centers in fine-chemical synthesis and enantiospecific
      synthesis of a variety of carboxylic acid derivatives. In this review, the
      literature has been surveyed to provide a comprehensive coverage of the
      application of nitrilases in organic synthesis. Literature has also been cited to
      describe the isolation and/or characterization of nitrilases and related enzymes.

PMID- 17193243
TI  - The distribution of iron oxidation states in a constructed wetland as an
      indicator of its redox properties.
AB  - Wastewater-treatment processes taking place inside constructed wetlands are
      closely connected with chemical properties of these systems. The aeration of a
      wetland via the roots of the vegetation (and a subsequent formation of redox
      potential gradients) strongly influences the wastewater treatment efficiency, and
      thus it represents one of the most important characteristics of the wetland. The
      concentration ratios of individual iron oxidation states (Fe(II) and Fe(III))
      were determined as the indicator of the redox properties of the constructed
      wetland reed bed during this study. Interstitial water from the wetland was
      sampled eleven times throughout the year 2005. The spectrophotometric method
      using 1,10-phenanthroline was properly optimized (limits of detection and
      quantification, sensitivity, linear dynamic range, repeatability, and accuracy
      values were assessed) and applied for iron determination. Most of iron, ca. 98%,
      is reduced to the Fe(II) form in raw wastewater and water from the inflow zone of
      the constructed wetland, however, at the outflow and in the vegetation bed both
      iron oxidation states are usually detected. The presence of Fe(III) in the reed
      bed (ca. 10-30% for some samples) demonstrates the aeration of the wetland by the
      vegetation (Phragmites australis) resulting in a re-oxidation of Fe(II).

PMID- 17193244
TI  - A study on medicinal plants from Malaysia focused on Acalypha siamensis Oliv. ex
      Gage. isolation and structure of a new tetraterpene, acalyphaser A.
AB  - As a part of our chemical studies on Malaysian medicinal plants, five Malaysian
      plant species were evaluated by cytotoxicity assays using P388 murine leukemia
      cells. Since Acalypha siamensis exhibited the strongest growth inhibition, its
      constituents were studied as the object of search for bioactive materials. A
      novel tetraterpene, acalyphaser A (1), was isolated in the course of the
      purification. Its structure was elucidated on the basis of 1D- and 2D-NMR
      techniques, and mass spectrometry.

PMID- 17193245
TI  - A variety of volatile compounds as markers in unifloral honey from dalmatian sage
      (Salvia officinalis L.).
AB  - Volatile compounds of unifloral Salvia officinalis L. honey has been investigated
      for the first time. The botanical origin of ten unifloral Salvia honey samples
      has been ascertained by pollen analysis (the honey samples displayed 23-60% of
      Salvia pollen). Fifty-four volatile compounds were identified by GC and GC/MS in
      ten Salvia honey extracts obtained by ultrasound-assisted extraction (USE) with
      pentane/Et(2)O 1 : 2. The yield of isolated volatiles varied from 25.7 to 30.5 mg
      kg(-1). Salvia honey could be distinguished on the basis of the high percentage
      of benzoic acid (6.4-14.8%), and especially phenylacetic acid (5.7-18.4%). Minor,
      but floral-origin important volatiles were identified such as shikimate pathway
      derivatives, 'degraded-carotenoid-like' structures (3,5,5-trimethylcyclohex-2-ene
      derivatives) and 2,6,6-trimethylcyclohex-2-ene derivatives. Compounds from other
      metabolic pathways such as aliphatic acids and higher linear hydrocarbons, as
      well as heterocycles (pyrans, furans, and pyrroles), were also present. Most of
      the identified compounds do not constitute specific Salvia honey markers, due to
      their presence in honeys of other botanical origins; however, their ratio in
      different honeys could be useful to distinguish floral origin. Salvia-honey
      volatile markers were: benzoic acid, phenylacetic acid, p-anisaldehyde, alpha
      isophorone, 4-ketoisophorone, dehydrovomifoliol, 2,6,6-trimethyl-4-oxocyclohex-2
      ene-1-carbaldehyde, 2,2,6-trimethylcyclohexane-1,4-dione, and coumaran.

PMID- 17193246
TI  - New phenolic constituents from Balanophora polyandra with radical-scavenging
      activity.
AB  - The 80% acetone extract of Balanophora polyandra Griff. (Balanophoraceae) was
      found to exhibit high radical-scavenging activity (SC(50)=14.48 mug/ml) towards
      1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Further chemical investigation led
      the isolation of two new hydrolysable tannins, balapolyphorins A (1) and B (2),
      together with 20 known phenolic compounds (3-22). Their structures were
      established by detailed spectroscopic analysis, and the radical-scavenging
      properties of all isolated compounds were determined by DPPH assay.

PMID- 17193247
TI  - Enzymatic degradation of beta- and mixed alpha,beta-oligopeptides.
AB  - One of the main and most astonishing characteristics of peptides comprised of
      beta-amino acids with proteinogenic side chains is their extraordinarily high
      stability towards enzymatic degradation. So far, only certain microbial enzymes
      have been shown to cleave N-terminal beta(3)-homoamino acid residues from
      peptides. In this work, the L-aminopeptidase-D-amidase/esterase (DmpA) from
      Ochrobactrum anthropi LMG7991 is compared to two closely related beta-peptidyl
      aminopeptidases (BapA), which originate from Sphingosinicella strains, and to
      microsomal leucine aminopeptidase (LAP) as a reference. All four enzymes are
      aminopeptidases cleaving N-terminal amino acids from small peptides. Degradation
      experiments reveal that DmpA and both BapA enzymes exhibit unique, but clearly
      distinct substrate specificities and preferences. DmpA also cleaves beta- and
      mixed alpha,beta-peptides and amides, but a short side chain of the N-terminal
      beta-amino acid residue seems to be a prerequisite, since only peptides carrying
      N-terminal betahGly and beta(3)hAla are hydrolyzed with good efficiencies. Both
      beta-peptidyl aminopeptidases cleave beta-amino acids from a variety of beta
      peptides and mixed alpha,beta-peptides, but they do not accept alpha-amino acids
      in the N-terminal position. Astonishingly, DmpA exhibited much higher catalytical
      rates for the mixed dipeptide carnosine (H-betahGly-His-OH) than for any other
      substrate described until now.

PMID- 17193248
TI  - Cytotoxic steroidal saponins from Polygonatum punctatum.
AB  - Four new steroidal saponins, polypunctosides A-D (1-4, resp.), were isolated from
      the rhizomes of Polygonatum punctatum, together with five known steroidal
      saponins. On the basis of chemical and spectral evidence, the structures of the
      new saponins were established as (3beta,23S,25R)-23-(alpha-L
      arabinopyranosyloxy)spirost-5-en-3-yl 4-O-(6-deoxy-alpha-L-mannopyranosyl)-D
      glucopyranoside (1), (3beta,23S,25R)-23-[(2-O-acetyl-alpha-L
      arabinopyranosyl)oxy]spirost-5-en-3-yl 4-O-(6-deoxy-alpha-L-mannopyranosyl)-D
      glucopyranoside (2), (3beta,23S,25R)-23-[(3-O-acetyl-alpha-L
      arabinopyranosyl)oxy]spirost-5-en-3-yl 4-O-(6-deoxy-alpha-L-mannopyranosyl)-D
      glucopyranoside (3), and (3beta,23S,25R)-23-[(4-O-acetyl-alpha-L
      arabinopyranosyl)oxy]spirost-5-en-3-yl 4-O-(6-deoxy-alpha-L-mannopyranosyl)-D
      glucopyranoside (4). The cytotoxic activity of the isolated saponins was
      evaluated towards HeLa cells.

PMID- 17193251
TI  - 5-(pyrrolidin-2-yl)-1H-tetrazole and 5-[(pyrrolidin-2-yl)methyl]-1H-tetrazole:
      proline surrogates with increased potential in asymmetric catalysis.
AB  - Catalytic enantioselective methodology has dramatically been enriched by the re
      discovery of the simple amino acid proline as a chiral catalyst in the year 2000.
      Although no catalyst offers such a simple and broad access to quite complex
      reaction products, as does proline, its synthetic potential is not unrestricted,
      what is especially connected to its poor solubility in organic media. Exchange of
      the carboxylic moiety by a tetrazole unit leads to proline surrogates, that by
      far outperform proline with respect to yield, enantioselectivity, reaction time,
      substrate and solvent scope, catalyst loading, and stoichiometry of the compounds
      used in excess. These factors are discussed and critically compared with selected
      representative proline-catalyzed reactions.

PMID- 17193252
TI  - Lipophilicity plays a major role in modulating the inhibition of monoamine
      oxidase B by 7-substituted coumarins.
AB  - A series of coumarin derivatives (1-22), bearing at the 7-position ether, ketone,
      ester, carbamate, or amide functions of varying size and lipophilicity, were
      synthesized and investigated for their in vitro monoamine oxidase-A and -B (MAO-A
      and -B) inhibitory activities. Most of the compounds acted preferentially as MAO
      B inhibitors, with IC(50) values in the micromolar to low-nanomolar range. A
      structure-activity-relationship (SAR) study highlighted lipophilicity as an
      important property modulating the MAO-B inhibition potency of 7-substituted
      coumarins, as shown by a linear correlation (n=20, r(2)=0.72) between pIC(50) and
      calculated log P values. The stability of ester-containing coumarin derivatives
      in rat plasma provided information on factors that either favor (lipophilicity)
      or decrease (steric hindrance) esterase-catalyzed hydrolysis. Two compounds (14
      and 22) were selected to investigate how lipophilicity and enzymatic stability
      may affect in vivo MAO activities, as assayed ex vivo in rat. The most-potent and
      -selective MAO-B inhibitor 22 (=7-[(3,4-difluorobenzyl)oxy]-3,4-dimethyl-1
      benzopyran-2(2H)-one) within the examined series significantly inhibited (>60%)
      ex vivo rat-liver and striatal MAO-B activities 1 h after intraperitoneal
      administration of high doses (100 and 300 mumol kg(-1)), revealing its ability to
      cross the blood-brain barrier. At the same doses, liver and striatum MAO-A was
      less inhibited in vivo, somehow reflecting MAO-B selectivity, as assessed in
      vitro. In contrast, the metabolically less stable derivative 14, bearing an
      isopropyl ester in the lateral chain, had a weak effect on hepatic MAO-B activity
      in vivo, and none on striatal MAO-B, but, surprisingly, displayed inhibitory
      effects on MAO-A in both peripheral and brain tissues.

PMID- 17193253
TI  - Chiral multidimensional gas chromatography (MDGC) and chiral GC-olfactometry with
      a double-cool-strand interface: application to malodors.
AB  - Volatile sulfur compounds such as 3-methyl-3-sulfanylhexan-1-ol (1) are largely
      responsible for axillary-sweat malodors. In this work, we describe the
      determination of the enantiomer ratio of the trace constituent 1 and the odor
      description of its antipodes (R)- and (S)-1 by means of multidimensional gas
      chromatography (MDGC) in combination with chiral gas chromatography-olfactometry
      (GC-O). This technique allowed the on-line evaluation of the sensory character of
      both enantiomers via a sniffing port, and is based on a novel double-cool-strand
      interface (DCSI). First, the system's inertness was tested towards the labile
      compound 2-methylfuran-3-thiol (MFT; 2). Then, the DCSI was used in a new
      configuration to achieve olfactive characterization by means of chiral GC-O. In
      contrast to direct smelling after the chiral column, our technique allows, for
      the first time, to significantly delay the perception of the second-eluting
      enantiomer after the first one. This lowers the risk of sensory saturation, as
      the panelist can recover from the first stimulus, before evaluating the second
      one. To help programming the DCSI, a dedicated program was set up. The enantiomer
      ratio of the sweat malodor 1 was determined as (S)/(R) 3 : 1, and the dominating
      (S)-isomer was shown to largely impart its specific character to the overall odor
      of the sweat extract.

PMID- 17193254
TI  - Sorption of chromium(VI) from aqueous solution by cassava (Manihot sculenta
      Cranz.) waste biomass.
AB  - The sorption of highly toxic Cr(VI) ions by cassava waste biomass was
      quantitatively investigated. The sorption was found to be influenced by several
      physico-chemical factors such as agitation speed, temperature, contact time, pH,
      and sorbent/sorbate ratio. The adsorption data at equilibrium were fitted to
      Freundlich and Langmuir isotherms. The monolayer sorption capacity was found to
      be 61.79 mg of Cr(VI) per gram of biomass. The kinetics of Cr(VI) adsorption to
      pure cassava-tuber-bark wastes were determined based on a pseudo-second-order
      rate model using the batch-sorption technique at a temperature of 30 degrees. The
      kinetics data suggest that the adsorption process is exothermic, and that the
      rate-limiting step is physisorption. Negative DeltaG(ads) values indicate that
      the adsorption is spontaneous and exothermic in nature. Also, under optimal
      conditions (in agitated 1M H(2)SO(4) at 30 degrees), the cassava waste biomass
      appears to be recyclable.

PMID- 17193255
TI  - New clerodane diterpenoids from the aerial parts of Pulicaria wightiana.
AB  - Two new ent-clerodane-type diterpenoids, compounds 1 and 2, were isolated from
      the aerial parts of Pulicaria wightiana, together with three known constituents.
      Their structures were established based on spectroscopic data, and their
      antibacterial activities were evaluated (Table 2).

PMID- 17193256
TI  - Daturametelins H, I, and J: three new withanolide glycosides from Datura metel L.
AB  - Three new withanolide glycosides named daturametelins H-J (1-3), together with
      two known ones, daturataturin A (4) and 7,27-dihydroxy-1-oxowitha-2,5,24
      trienolide (5), were isolated from the MeOH extract of the aerial parts of Datura
      metel L. (Solanaceae). Their structures were determined mainly by spectroscopic
      techniques including 2D-NMR (HMBC, HMQC, (1)H,(1)H-COSY, NOESY) and MS
      experiments. Compounds 1-5 were tested for their antiproliferative activity
      towards the human colorectal carcinoma (HCT-116) cell line. The nonglycosidic
      compound 5 exhibited the highest activity of the tested withanolides, with an
      IC(50) value of 3.2+/-0.2 microM (Table 3).

PMID- 17193257
TI  - Ginsenoside Rd from Panax notoginseng is cytotoxic towards HeLa cancer cells and
      induces apoptosis.
AB  - The saponin ginsenoside Rd (1), isolated from Panax notoginseng, is used for the
      treatment of cardiovascular diseases, inflammation, different body pains, trauma,
      and internal and external bleeding due to injury. In this study, we report that 1
      inhibits the cell growth of human cervical cancer (HeLa) cells in a concentration
      and time-dependent manner, with an IC(50) value of 150.5+/-0.8 mcirog/ml after
      48 h of incubation. The drug-treated cells displayed features of apoptosis,
      including typical morphological characteristics and formation of DNA ladders, as
      evident from agarose-gel electrophoresis. Flow-cytometric analysis showed that
      the cell-cycle distribution of HeLa cells exposed to 1 is characterized by a
      decrease of the G(0)/G(1)-phase and an increase of the S-phase cells,
      respectively, in a dose-dependent manner. The apoptotic rate of HeLa cells
      treated for 48 h with 210 microg/ml of 1 was 35.8%. Further, 1 was found to
      increase the expression of Bax and to decrease the expression of Bcl-2 proteins,
      respectively, and to lower the mitochondrial transmembrane potential of HeLa
      cells. The caspase-3 inhibitor DEVD-CHO (at 2 microM) increased the viability of
      HeLa cells treated with 1. Taken together, our study suggests that ginsenoside Rd
      (1) significantly inhibits HeLa cell proliferation, and induces cell apoptosis
      through down-regulating Bcl-2 expression, up-regulating Bax expression, lowering
      the mitochondrial transmembrane potential, and activating the caspase-3 pathway.
      Thus, 1 could serve as a lead to develop novel chemotherapeutic or
      chemopreventive agents against human cervical cancer.

PMID- 17193258
TI  - A novel type of membrane based on cholesteryl phosphocholine, cholesteryl
      phosphate, or sitosteryl phosphate, and dimyristoylglycerol.
AB  - Mixtures of amphiphilic cholesteryl phosphate (CP), sitosteryl phosphate (SP), or
      cholesteryl phosphocholine (CPC) with the nonphosphoryl diacyl lipid
      dimyristoylglycerol (DMG) or with cholesterol give self-organized systems (giant
      vesicles) in a wide range of pH, as demonstrated by fluorescence microscopy,
      differential scanning calorimetry, and small-angle X-ray scattering. The water
      permeability of a 1 : 1 molar mixture of CPC and DMG was also measured by a
      stopped-flow/light-scattering method. The novel self-organized systems are akin
      to natural eukaryotic ones, the only difference being the site of the phosphate
      containing head-group, located on cholesterol instead of DMG. They might be
      present in some organisms not yet studied for the composition of their membranes.

PMID- 17193259
TI  - The chemical constituents of the fungus Stereum sp.
AB  - Four new compounds, including a sesquiterpene and three aromatic compounds, and a
      known compound were isolated from a culture broth of the fungus Stereum sp. The
      novel sesquiterpene was determined to be stereumone A ((+)-2,3,4a,5,6,7,8a,9
      octahydro-5-hydroxy-6,6,9-trimethyl-4,8a-epoxynaphtho[2,3-b]furan-8(8H)-one; 1),
      and the three new aromatic compounds were elucidated as 3,5-dihydroxy-4-(3
      methylbut-2-enyl)benzene-1,2-dicarbaldehyde (2), 5,7-dihydroxy-6-(3-methylbut-2
      enyl)isobenzofuran-1(3H)-one (3), butyl 2,4-dihydroxy-6-methylbenzoate (4),
      together with the known compound methyl 2,4-dihydroxy-6-methylbenzoate (5). The
      structures were established by spectroscopic methods including 2D-NMR techniques.
      Compounds 2 and 4 showed evident nematicidal activity against nematode
      Panagrellus redivivus.

PMID- 17193260
TI  - Anthracobic acids A and B, two polyketides, produced by an endophytic fungus
      Anthracobia sp.
AB  - Two new polyketides, anthracobic acids A and B (1 and 2, resp.), were isolated
      from a cultured endophytic fungus, Anthracobia sp. The NMR study revealed that
      both anthracobic acids contain a carboxylic acid conjugated tetraene attached to
      an octahydronaphthalene moiety. Both compounds showed antimicrobial activity.

PMID- 17193261
TI  - New antioxidant phenolic glycosides from Walsura yunnanensis.
AB  - Four new polyphenolic glycosides (1-4) were isolated from the BuOH extract of the
      bark of Walsura yunnanenis C. Y. Wu. These compounds comprise two lignans, i.e.,
      the 9-O-alpha-L-arabinopyranosides 1 and 2 of (-)-isolariciresinol and of (+)-5
      methoxyisolariciresinol, respectively, and the two phenolic glycosides 3,4,5
      trimethoxyphenyl 2-O-(alpha-L-fucopyranosyl)-beta-D-glucopyranoside (3) and 3,5
      dihydroxyphenyl 6-O-(4-hydroxy-3,5-dimethoxybenzoyl)-beta-D-glucopyranoside
      (walsuraside; 4). In addition, three known compounds, 3,4,5-trimethoxyphenyl beta
      D-glucopyranoside, asperglaucide, and butyl alpha-D-fructofuranoside were
      identified. Their structures were elucidated spectroscopically and by chemical
      transformation (hydrolysis). The new compounds 1, 2, and 4 displayed significant
      antioxidant activities, with IC(50) values in the range of ca. 42 to 49
      microg/ml.

PMID- 17193262
TI  - Ternary nickel(II) complexes as hydrolytic DNA-cleavage agents.
AB  - A series of small model complexes made from Ni(II) and the ligands
      ethylenediamine (en), histamine (hist), and histidylleucine (HisLeu) were
      prepared and studied as potential hydrolytic DNA-cleavage agents. The stability
      constants and species-distribution curves for these complexes were determined as
      a function of pH. The 1 : 1 : 1 ternary complexes [Ni(II)(en)(HisLeu)] (1) and
      [Ni(II)(hist)(HisLeu)] (2) were the only major species present at the
      physiologically relevant pH of 6-7, as further corroborated by ESI-MS analysis.
      The complex geometries of 1 and 2 were analyzed by UV/VIS experiments and
      molecular dynamics (MD) simulations. Both ternary complexes were found to
      intercalate with DNA, as shown by UV/VIS, thermal-denaturation, and fluorescence
      titration studies with ethidium bromide (EB). The intrinsic binding constants
      (K(b)) for the bound complexes 1DNA and 2DNA were determined as 150 and 290,
      resp. Gel-electrophoresis experiments revealed that 1 and 2 cleave supercoiled
      (type-I) to nicked-circular (type-II) DNA at physiological pH, with rate
      constants of 0.64 and 0.75 h(-1), resp. A tentative mechanism for this hydrolytic
      cleavage is proposed.

PMID- 17193263
TI  - Conformational fluctuations versus constraints in amino acid side chains: the
      evolution of information content from free amino acids to proteins.
AB  - Like all other complex biological systems, proteins exhibit properties not found
      in free amino acids (i.e., emergent properties). Here, we explore top-down
      constraints experienced by the residue side chains in proteins compared to amino
      acids in increasingly complex molecular environments: free amino acids, end
      capped amino acids, and the central residue in an alpha-helical nonapeptide. The
      crystalline structure of the contractile protein profilin Ib and the enzyme
      trypsin were chosen as objects of study, and submitted to 10 ns molecular
      dynamics (MD) simulations. The results revealed increased conformational
      constraints on the side chains when going from the simpler to the more complex
      compounds. A Shannon entropy (SE) analysis of the conformational behavior of the
      side chains showed in most cases a progressive and marked decrease in the SE of
      the chi1 and chi2 dihedral angles. This is equivalent to stating that
      conformational constraints on the side chain of residues increase their
      information content and, hence, recognition specificity compared to free amino
      acids. In other words, the vastly increased information content of a protein
      relative to its free monomers is embedded not only in the tertiary structure of
      the backbone, but also in the conformational behavior of the side chains. The
      postulated implication is that both backbone and side chains, by virtue of being
      conformationally constrained, contribute to the protein's recognition specificity
      toward other macromolecules and ligands.

PMID- 17193264
TI  - Synthesis and characterization of a C6 nucleoside analogue for the in vivo
      imaging of the gene expression of herpes simplex virus type-1 thymidine kinase
      (HSV1 TK).
AB  - The synthesis and biological evaluation of '6-(1,3-dihydroxyisobutyl)thymine'
      (DHBT; 1), which corresponds to 6-[3-hydroxy-2-(hydroxymethyl)propyl]-5
      methylpyrimidine-2,4(1H,3H)-dione, is reported. DHBT (1) was designed as a new
      substrate for herpes simplex virus type-1 thymidine kinase (HSV1 TK). The
      compound was found to be exclusively phosphorylated by HSV1 TK, and to exhibit
      good binding affinity (Ki = 35.3+/-1.3 microM). Cell-proliferation assays with
      HSV1-TK-transduced human osteosarcoma cells (143B-TK+-HSV1-WT) and with both
      human-thymidine-kinase-1-negative (143B-TK-) and non-transduced parental (MG-63)
      cells indicate that 1 is less cytotoxic than the standard drug Ganciclovir. Thus,
      DHBT (1) represents a promising precursor of a nontoxic reporter probe for the
      monitoring of HSV1 TK gene expression by means of positron-emission tomography
      (PET).

PMID- 17193265
TI  - Thermal stability of dehydrophenylalanine-containing model peptides as probed by
      infrared spectroscopy: a case study of an alpha-helical and a 3(10)-helical
      peptide.
AB  - The temperature-dependent secondary-structural changes in the two known helical
      model peptides Boc-Val-deltaPhe-Ala-Leu-Gly-OMe (1; alpha-helical) and Boc-Leu
      Phe-Ala-deltaPhe-Leu-OMe (2; 3(10)-helical), which both comprise a single
      dehydrophenylalanine (deltaPhe) residue, were investigated by means of FT-IR
      spectroscopy (peptide film on KBr). Both the first-order and the better-resolved
      second-order derivative IR spectra of 1 and 2 were analyzed. The nu(NH) (3240
      3340 cm(-1)), the Amide-I (1600-1700 cm(-1)), and the Amide-II (1510-1580 cm(-1))
      regions of 1 and 2 showed significant differences in thermal-denaturation
      experiments (22 degrees --> 144 degrees), with the 3(10)-helical peptide (2)
      being considerably more stable. This observation was rationalized by different
      patterns and strengths of intramolecular H-bonds, and was qualitatively related
      to the different geometries of the peptides. Also, a fair degree of residual
      secondary-structural elements were found even in the 'denatured' states above 104
      degrees (1) or 134 degrees (2).

PMID- 17193266
TI  - Synthesis of aminooxy-functionalized lanthanide(III) chelates for carbonyl-group
      conjugation.
AB  - The syntheses of three new aminooxy-tethered lanthanide(III) chelates, compounds
      1-3, incorporating DOTA (= 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
      acid), DTPA (= diethylenetriaminepentaacetic acid), or a substituted terpyridine
      (2,2',2'',2'''-[2,2': 6',2''-terpyridine-6,6''
      diylbis(methylenenitrilo)]tetraacetic acid), respectively, are described.
      Reagents 1-3 can be used for carbonyl 'labeling', as shown by the formation of
      the corresponding oxime-ether bioconjugates of naltrexone (16) and 2-deoxy-beta-D
      glucose (17) (Scheme 4).

PMID- 17193267
TI  - Synthesis of novel 3-(alkylcarbamoyl)-2-aryl-1,2-dihydro-6,7-(methylenedioxy)-3H
      quinazolin-4-ones as anticonvulsant agents.
AB  - A series of 3-(alkylcarbamoyl)-2-aryl-1,2-dihydro-6,7-(methylenedioxy)-3H
      quinazolin-4-ones, compounds 3-6, were synthesized, and screened as
      anticonvulsant agents in DBA/2 mice against sound-induced seizure (Table). The
      new compounds were found to display anticonvulsant properties inferior to those
      of the known dehydro congeners 1 and 2. The binding affinities of 1-6 at the AMPA
      and NMDA receptors were also evaluated.

PMID- 17193268
TI  - Synthesis and characterization of a new macrocyclic copper(II) complex with an N
      glycosidic pendant arm: in vitro cytotoxicity and binding studies with calf
      thymus DNA.
AB  - The new macrocyclic complex 2-amino-2-deoxy-N-[2-(1,3,5,8,11
      pentaazacyclotridecan-3-yl)ethyl]-beta-D-glucopyranosylamine copper(II)
      dichloride (1a) was prepared and thoroughly characterized by various techniques.
      Molar-conductance measurements showed that 1a (and its Ni analogue 1b) are ionic
      in nature. On the basis of spectroscopic data, both complexes were assigned a
      square-planar geometry, and found to be highly stabile and hydrolytically robust
      in H2O over a wide range of pH, as confirmed by cyclic voltammetry (CV). The
      Cu(II) complex 1a was found to bind to CT-DNA, with a binding constant Kb of
      2.4x10(3) M(-1), as derived by UV/VIS titration, and confirmed by CV, circular
      dichroism (CD), and viscosity measurements. DNA binding seems to occur mostly via
      H-bonding. In an in vitro antitumor MTT assay, 1a exhibited significant
      anticancer activity against the SY5Y and PC-12 cell lines, with an estimated IC50
      value in the micromolar range for SYSY, similar to the standard drug 5
      fluorouracil.

PMID- 17193269
TI  - Synthesis of fluoro analogues of 3,4-(methylenedioxy)amphetamine (MDA) and its
      derivatives.
AB  - The role of the metabolism of the entactogen 3,4-(methylenedioxy)methamphetamine
      (MDMA; 1b) in neurotoxic or psychopharmacologic action is widely discussed, but
      not yet fully understood. To prompt further investigation into the role of MDMA
      metabolism, six new 3,4-(difluoromethylenedioxy) analogues of MDMA (1b) were
      prepared and characterized. Although electronically very different, the fluoro
      analogues 3-5 should be sterically very similar to the non-fluorinated parent
      compounds. The F-atoms may prevent the formation of toxic metabolites produced
      via a radical pathway (Scheme 1). Different theories regarding MDMA-induced
      neurotoxicity are briefly reviewed and discussed. The novel compounds 3-5 may
      help to verify the hypothesis that MDMA-induced neurotoxicity is the result of
      the formation of metabolites lacking the methylenedioxy bridge.

PMID- 17193270
TI  - New chemical constituents from the endophyte Streptomyces species LR4612
      cultivated on Maytenus hookeri.
AB  - From solid cultures of the biologically important endophyte Streptomyces species
      LR4612, cultivated on Maytenus hookeri, four new and two known compounds were
      isolated. The new compounds were identified as (2S*,3S*)-5-amino-3-hydroxy-5
      oxopentan-2-yl 3-(formylamino)-2-hydroxybenzoate (1), N-[(3R*,4R*)-3-amino-3,4
      dihydro-4-methyl-2,6-dioxo-2H,6H-1,5-benzodioxocin-10-yl]formamide (2),
      (5beta,6alpha)-6,11-dihydroxyeudesmane (3), and 5-(6,7-dihydroxy-6
      methyloctyl)furan-2(5H)-one (4); the known compounds were elucidated as
      sorbicillin (5) and N-acetyltyramine (6). The structures were established by HR
      ESI-MS and in-depth NMR analyses.

PMID- 17193271
TI  - Antiviral flavonoid-type C-glycosides from the flowers of Trollius chinensis.
AB  - Two new flavonoid-type C-glycosides, trollisin I (= (1S)-1,5-anhydro-1-[2-(3,4
      dihydroxyphenyl)-5-hydroxy-7-methoxy-4-oxo-4H-[1]benzopyran-8-yl]-2-O-(2
      methylbutanoyl)-D-glucitol; 1) and its 2-O-benzoyl congener trollisin II (2),
      were isolated from Trollius chinensis Bunge, together with the two known
      compounds 2''-O-(2'''-methylbutanoyl)isoswertisin (3) and vitexin galactoside
      (4). All compounds were identified by HR-ESI-MS and in-depth NMR-spectroscopic
      analyses. In antiviral assays, compound 3 was found to be moderately active
      towards influenza virus A.

PMID- 17193272
TI  - 13C-NMR study of the ruthenium(II)-catalyzed degradation of labeled G-factor
      endoperoxides: proposal of a likely biogenetic pathway and evidence for CO2
      release.
AB  - G-factor endoperoxides are natural products acting as phytohormones and
      contribute to root inhibition and frost resistance in Eucalyptus grandis and
      other Myrtaceae. Several (Z)- and (E)-configured cyclopentane-1,3-dione
      metabolites of G-factors have been found in some Eucalyptus extracts.
      Interestingly, these probable metabolites are identical to the products obtained
      by Ru(II)-catalyzed reduction of G-factors. In the present work, we, thus,
      studied the mechanism involved in the formation of these compounds by means of in
      depth NMR distribution analysis of two differently 13C-labeled G3-factors. The
      observed CO2 release is underlined, and a comparison with the corresponding
      Fe(II)-induced degradation of G-factor endoperoxides is made. Also, the type of
      electron transfer proposed in the two processes is discussed and, tentatively,
      connected to the role of endoperoxides in plants.

PMID- 17193273
TI  - Phylogeny of the Schisandraceae based on cpDNA mat-K and rpL16 intron data.
AB  - The chloroplast mat-K region and rpL16 intron region were sequenced for 14
      species of Schisandraceae, representing both genera Kadsura Kaempf. ex Juss. and
      Schisandra Michx, to discuss the phylogeny of this family. Analyses were
      performed both in separate and combined sequence data sets (including the rbc-L
      sequence), with Illicium angustispealum A. C. Smith as the out-group. The results
      showed that the Schisandraceae are monophyletic. In all the analyses, Schisandra
      propinqua var. chinensis Oliva and Schisandra plena A. C. Smith were nested
      within Kadsura, which implies that the genera Kadsura and Schisandra are closely
      related. They might have originated from a common ancestor, but then evolved via
      different routes. The result inferred from the combined data showed a greater
      resolution within Schisandra than those from the two separate data sets. High
      bootstrap values supported the monophyly of most subgenera according to Law's
      system (1996). A combination of morphological, anatomical, and chemical analyses
      indicates that S. chinensis and S. rubriflora may be the primitive taxa in
      Schisandra.

PMID- 17193274
TI  - Chemical constituents of plants from the genus Inula.

PMID- 17193275
TI  - [4-(2H-1,2,3-benzotriazol-2-yl)phenoxy]alkanoic acids as agonists of peroxisome
      proliferator-activated receptors (PPARs).
AB  - A series of [4-(2H-1,2,3-benzotriazol-2-yl)phenoxy]alkanoic acids has been
      synthesized and tested as agonists of Peroxisome Proliferator-Activated Receptor
      (PPAR) alpha, gamma, and delta. Three compounds displayed 56 to 96% of maximal
      activity of the reference drug Wy-14643 on PPARalpha, and two of these, i.e., 1
      and 5, exhibited also moderate activity on either PPARgamma or delta with
      efficacy equal to 50% and 46% of that of rosiglitazone and GW 501516,
      respectively. Thus, compounds 1 and 5 represent interesting starting point for
      preparing novel agents for the treatment of dyslipidemia or of dyslipidemic type
      2 diabetes.

PMID- 17193276
TI  - Synthesis and biological evaluation of N-(arylsulfanyl)carbonyl analogues of
      paclitaxel (taxol).
AB  - Four new N-(arylsufanyl)carbonyl paclitaxel analogues (2a-d) were prepared from 7
      (triethylsilyl)-protected baccatin III (5). Their cytotoxicities against human
      ovarian (A2780) and prostate cancer (PC3) cell lines, as well as their tubulin
      assembly activities, were determined. In these assays, the new compounds showed
      rather weak activities, one two orders of magnitude below those of paclitaxel
      (taxol; 1). The known 3'-N-[(thiophen-2-yl)carbonyl] paclitaxel analogue 3 was
      also prepared. As previously reported, 3 exhibited strongly improved
      cytotoxicities and tubulin-assembly activities as compared to paclitaxel (1).

PMID- 17193277
TI  - Structurally unique biflavonoids from Selaginella chrysocaulos and Selaginella
      bryopteris.
AB  - Chemical investigation of Selaginella chrysocaulos from Northeast India yielded
      three new (i.e., 1-3) and two known biflavonoids. From Selaginella bryopteris,
      collected in the southern part of India, one new (11) and eleven known
      biflavonoids of the amentoflavone- and hinokiflavone-type were isolated and
      identified. The structures of the compounds were elucidated by 1D- and 2D-NMR
      spectroscopy, and by mass spectrometry. The absolute configurations of chiral
      biflavonoids with flavanone subunits (from S. bryopteris) were determined with
      the aid of circular-dichroism (CD) spectroscopy. Several very rare or even
      unprecedented substructures in biflavonoids were found.

PMID- 17193278
TI  - Bioassay for the determination of the intra- and extracellular activity of
      aminopeptidases in immobilized tomato cells.
AB  - Permeabilized tomato cells were cross-linked with glutaraldehyde in the absence
      of a carrier. The immobilized cells demonstrated significantly lower
      aminopeptidase (AP) activities than untreated control cells. However, when
      immobilized with pectate and alginate gels, the tomato cells retained their AP
      activities. A new method for the determination of the activity of both extra- and
      intracellular AP was developed, based on enzyme-catalyzed hydrolysis of a series
      of synthetic beta-naphthylamides (betaNA) of the L-amino acids Ala, Arg, Leu,
      Pro, Tyr, or of the synthetic beta-methoxynaphthylamides (betaMNA) of Ala and
      Arg. Extracellular AP--produced by calli, cell-suspension culture, or seedlings
      of tomato cells grown on agar--hydrolyzed these peptidic substrates to the free
      naphthalene amines and amino acids. Staining with Fast Garnet GBC salt under
      formation of bright reddish azo dyes readily allowed the determination of AP
      activities. For the tomato-cell suspension, the intracellular activity accounted
      for 91.3-93.9% of the total activity, and the extracellular one for 6.1-8.7%,
      respectively. Our method permits the rapid, simple, and specific determination of
      plant aminopeptidases.

PMID- 17193279
TI  - Attenuation of petroleum hydrocarbons by weathering: a case study.
AB  - Possible alterations in the distribution and composition of total petroleum
      hydrocarbon (TPH), polycyclic aromatic hydrocarbons (PAHs), and benzene, toluene,
      ethyl benzene, and xylene isomers (BTEX) in the released oil at Idu-Ekpeye in
      Niger Delta (Nigeria) were studied within two seasonal variations of two months
      and six months, with a view to assessing the level of attenuation of these
      hydrocarbons in impacted soils. Although there were significant contaminations in
      the kerosene range (n-C10-n-C14) two months after, especially of the n-C12 and n
      C13 fractions, the complete disappearance of the n-C8 to n-C23 hydrocarbons,
      including the acyclic isoprenoids (pristane and phytane), and the reduced amounts
      of PAHs, and BTEX, six months after, provided substantial evidence of attenuation
      as indicated in the reduction in total hydrocarbon content (THC) from 61.17 to
      42.86%. Soil physicochemical properties such as pH, moisture content, heavy
      metal, TOC, and TOM, all provided corroborative evidence of hydrocarbon
      attenuation. The pristane/phytane ratio of the spill samples suggests that the
      spilled oil was genetically oxic.

PMID- 17193281
TI  - A new S4-ligated zinc-peptide 1:2 complex for the hydrolytic cleavage of DNA.
AB  - A new sulfur-ligated Zn-peptide 1:2 complex, [Zn(II)(Boc-NH-Cys-Gly-Cys-OMe)2]2-
      (2), was prepared, characterized, and tested for its DNA-binding and -cleavage
      properties. Complex 2 was found to cleave DNA hydrolytically. The negative charge
      in 2 reduces the affinity of the complex for DNA, and enhances its binding
      specificity.

PMID- 17193280
TI  - Membrane properties of branched polyprenyl phosphates, postulated as primitive
      membrane constituents.
AB  - We have postulated earlier that the highly branched isoprenoid alkanes, which are
      distributed widely in many sediments, may have been derived from the
      corresponding branched polyprenyl phosphates, potentially present in biomembranes
      in primitive organisms. These polyprenyl-branched polyprenyl phosphates might be
      derived by a simple alkylation from non-substituted polyprenyl phosphates, which
      we postulate to be the precursors of all membrane terpenoids. We have now
      synthesized a series of 6-(poly)prenyl-substituted polyprenyl phosphates and
      studied the formation of vesicles from these phosphates, as a function of the
      substituted-chain length, the position of the double bond, and pH. Nine of the
      branched polyprenyl phosphates containing 20-30 C-atoms do form vesicles at a
      'physiological' pH; the lipophilicity/hydrophilicity ratio is as expected an
      important factor. We have also studied the water permeability through membranes
      of these branched polyprenyl phosphate vesicles by our stopped-flow/light
      scattering method. These highly branched polyprenyl phosphates can more
      effectively reduce the water permeability than non-substituted polyprenyl
      phosphates: the vesicles formed by the former are more stable against mechanical
      stress. This reinforces our hypothesis about the origin of the sedimentary
      polyprenyl-substituted polyprene hydrocarbons.

PMID- 17193282
TI  - Synthesis and cytotoxic evaluation of a series of genistein derivatives.
AB  - Thirty genistein (= 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; GEN)
      derivatives were synthesized from genistein through a facile approach in high
      yields. Compounds 9, 11, 12, 23-30 were reported for the first time, while 13-22
      have already been reported in our recent paper. The cytotoxic activities of these
      compounds were evaluated against a human nasopharyngeal epidermoid tumor cell
      line KB. Compounds 7-9, 12, 14, 16-19, 21, 24, 27, 29 showed remarkable antitumor
      activities in vitro, which was comparable with 5-fluorouracil, an anticancer
      drug. On the basis of the obtained experimental data, structure-effect
      relationships were discussed.

PMID- 17193283
TI  - Isolation, DNA topoisomerase-II inhibition, and cytotoxicity of three new
      terpenoids from the bark of Macaranga tanarius.
AB  - One new pimarane-type diterpenoid (1) and two new taraxerane-based triterpenoids
      (2 and 3) were isolated from the bark of Macaranga tanarius, along with seven
      known compounds. Their structures were identified by spectroscopic methods
      including NMR and MS analyses. Compounds 1-5 were tested for their in vitro
      inhibition of DNA topoisomerase II, as well as for their cytotoxicities against
      human lung carcinoma A549 cells (Table 3). The triterpenoids 2-5 showed strong
      activities in both assays, but the diterpenoid 1 was only moderately active.

PMID- 17193284
TI  - Muscarinic receptors: A comparative analysis of structural features and binding
      modes through homology modelling and molecular docking.
AB  - Three-dimensional models of the five human muscarinic receptors were obtained
      from their known sequences. Homology modelling based on the crystallographic
      structure of bovine rhodopsin yielded models compatible with known results from
      site-directed mutagenesis studies. The only exceptions were the cytoplasmic loop
      3 (CL3) in the five receptors, and the large C-terminal domain in M(1). Here,
      homology modelling with other closely related proteins allowed to solve these
      gaps. A detailed comparative discussion of the five models is given. The second
      part of the work involved docking experiments with the physiological ligand
      acetylcholine, again yielding results entirely compatible with results from
      mutagenesis experiments. The study revealed analogies and differences between the
      five receptors in the residues, and interactions leading to the recognition and
      binding of acetylcholine.

PMID- 17193285
TI  - Inhibition of histidine ammonia lyase by heteroaryl-alanines and acrylates.
AB  - Histidine ammonia lyase (HAL) catalyzes the elimination of ammonia from the
      substrate to form (E)-urocanate. The interaction between HAL and acrylic acids or
      alanines substituted with heteroaryl groups in the beta-position was
      investigated. These proved to be strong competitive inhibitors when the
      heteroaryl groups were furanyl, thiophenyl, benzofuranyl, and benzothiophenyl,
      carrying the alanyl or acrylic side chains either in 2 or 3 positions, with K(i)
      values between 18 and 139 microM. The exception was (furan-3-yl)alanine which was
      found to be inert. Tryptophan and 1-methyltryptophan, as well as the
      corresponding acrylates (=prop-2-enoates), are strong mixed inhibitors of HAL.
      Theoretically, L-histidine can be dissected into 4-methyl-1H-imidazole and
      glycine. Whereas these two compounds separately are only very weak inhibitors of
      HAL, equimolar amounts of both show a K(i) value of 1.7+/-0.09 mM which is to be
      compared with the K(m) value of 15.6 mM for the normal reaction. We conclude that
      5-methyl-1H-imidazole and glycine mimic the substrate and occupy the active site
      of HAL in a similar orientation.

PMID- 17193286
TI  - DNA containing side chains with terminal triple bonds: Base-pair stability and
      functionalization of alkynylated pyrimidines and 7-deazapurines.
AB  - The synthesis of a series of oligonucleotides containing 5-substituted
      pyrimidines as well as 7-substituted 7-deazapurines bearing diyne groups with
      terminal triple bonds is reported. The modified nucleosides were prepared from
      the corresponding iodo nucleosides and diynes by the Sonogashira cross-coupling
      reaction. They were converted into phosphoramidites and employed in solid-phase
      synthesis of oligonucleotides. The effect of the diyne modifications on the
      duplex stability was investigated. The modified nucleosides were used for further
      functionalization using the protocol of Huisgen-Sharpless [2+3] cycloaddition
      ('click chemistry').

PMID- 17193287
TI  - Nitroimidazoles, part 2: Synthesis, antiviral and antitumor activity of new 4
      nitroimidazoles.
AB  - A series of 5-alkylamino and 5-alkylsulfanyl derivatives of 1-aryl-2-alkyl-4
      nitro-1H-imidazoles 12-21, 31, and 34 were synthesized by a simple method with
      the aim to develop novel HIV non-nucleoside reverse transcriptase inhibitors
      (NNRTIs). All the new compounds were tested against HIV-1 and HIV-2 in MT-4
      cells. Compound 21, with an arylsulfanyl group at C(5) of the 4-nitro-1H
      imidazole backbone showed an EC(50) value of 0.22 microg/ml against HIV-1 with a
      therapeutic index of 13. This means that compound 21 was cytotoxic to MT-4 cells
      at a CC(50) value of 2.57 microg/ml; also compounds 8, 22-25, 28, and 29 were
      cytotoxic to MT-4 cells within the 0.4-4 microg/ml concentration range. Compounds
      8, and 12-21 were evaluated, as a rule, but found inactive at non-toxic
      concentrations against hepatitis C virus, herpes simplex type 1 and 2,
      cytomegalovirus (CMV), varicella-zoster virus (VZV), vaccinia virus, and
      vesicular stomatitis virus, and a number of other viruses. Yet, the therapeutic
      index of compounds 17 and 21 for CMV and VZV approached the tenfold cut-off
      point. Compounds 8 and 21 exhibited some cytostatic activity against leukemia and
      melanoma cell lines.

PMID- 17193288
TI  - Use of phospholipid transfer protein as a probe to study the lipid dynamics and
      alkaline phosphatase activity in the brush border membrane of human term
      placenta.
AB  - Incubation of placental brush border membrane (BBM) along with sonicated vesicles
      of exogenous lipids (egg yolk PC) in the presence of phospholipid-transfer
      protein (PL-TP) showed a decrease in the alkaline phosphatase activity due to the
      change in the membrane micro-environment, such as fluidity. Effect of substrate
      concentration was tested by Lineweaver-Burk plot, which showed decreased V(max)
      and K(M). The effect of temperature was probed by the Arrhenius plot, which
      showed no change in transition temperature, but a decline in the energy of
      activation both below and above the transition temperature. The protein-catalyzed
      transfer of phospholipid from the donor unilamellar vesicles resulted in a
      substantial increase in the BBM phospholipid and a net decrease in
      cholesterol/phospholipid molar ratio. The change in membrane fluidity was
      assessed by translational as well as rotational diffusion of membrane extrinsic
      fluorescent probes, pyrene and diphenyl-hexatriene. An increased lateral mobility
      was recorded by the increased pyrene excimer formation. A decrease in fluorescent
      polarization of diphenyl-hexatriene was observed, which led to the decrease in
      fluorescence anisotropy and order parameter, and therefore, an increase in
      membrane fluidity (rotational diffusion). Mean anisotropy parameter was also
      decreased in the presence of PL-TP. Thus, the placental BBM alkaline phosphatase
      activity showed a distinct lipid dependence which may have important
      physiological consequences.

PMID- 17193289
TI  - A fatal effect of hornet venom on rat-brain cortical neurons.
AB  - In a previous study, it was shown that the hornet venom or, more specifically,
      its venom sac extract (VSE) possesses deoxyribonuclease activity that exerts an
      effect both on insects as well as on mammals. We have now examined the effect of
      hornet VSE on primary culture of rat cortical neurons. Judging on the basis of
      our results, VSE induces a rapid cell death by a) permeabilizing the cell
      membrane, b) inducing DNA breaks, and c) cleaving the nuclear protein poly-ADP
      ribose polymerase (PARP-1), thereby preventing DNA repair.

PMID- 17193290
TI  - Syntheses and odor descriptions of cyclopropanated compounds, part 6: Analogs of
      aliphatic monoterpene dienols and non-branched alcohols.
AB  - Analogs of aliphatic monoterpene dienols (geraniol, nerol, linalool, and
      lavandulol) and non-branched alcohols (norleaf alcohol, matsutake alcohol, etc.)
      bearing a cyclopropane ring were synthesized, and their odor characteristics were
      examined. Most of the analogs show odor properties different from their parent
      compounds.

PMID- 17193292
TI  - Preliminary investigation on Mgbede-20 oil-polluted site in Niger Delta, Nigeria.
AB  - Soil physicochemical properties (pH, electrical conductivity (EC), % moisture,
      total organic carbon (TOC), total organic matter (TOM)), total extractable
      hydrocarbon content (THC), and micronutrient (Mn, Fe, Cu, Zn) levels of the
      Mgbede-20 oil-impacted site in Niger Delta, Nigeria, were investigated. Both oil
      impacted and their background control soils were found to be acidic especially at
      surface depth. A slightly higher EC value of 107.4+/-15.0 microS cm(-1) was
      obtained for the subsurface-polluted soils. Of the micronutrients investigated,
      only Fe exceeded its acceptable limit (>100 mg/kg). The observed increase in
      moisture content resulting from the oil's aggregation of soil particles may lower
      soil porosity, and increase resistance to penetration and hydrophobicity. Soil pH
      can be adjusted by aeration to complete the microbially mediated oxidation of the
      organic acids, followed by the addition of agricultural lime to provide some
      buffering capacity to the soil.

PMID- 17193291
TI  - Synthesis of new phytogrowth-inhibitory substituted aryl-p-benzoquinones.
AB  - Reaction of [(2-alkyloxy)methyl]-1,4-dimethoxybenzene 10 (alkyl=butyl, hexyl,
      decyl, tridecyl, tetradecyl, hexadecyl, and octadecyl) with ceric ammonium
      nitrate in order to produce p-benzoquinones (=cyclohexa-2,5-diene-1,4-diones)
      afforded 5-[(alkyloxy)methyl]-2-(4-formyl-2,5-dimethoxyphenyl)benzo-1,4-quinones
      12a-12g in yields that varied from 46 to 97%, accompanied by 2
      [(alkyloxy)methyl]benzo-1,4-quinones 11a-11g in only small quantities (< or =5%).
      These quinones resemble the natural phytotoxic compound sorgoleone, found in
      Sorghum bicolor. This reaction exemplifies a general procedure for the synthesis
      of novel aryl-substituted p-benzoquinones. The selective effects of compounds 12a
      12g, at the concentration of 5.5 ppm, on the growth of Cucumis sativus, Sorghum
      bicolor, Euphorbia heterophylla, and Ipomoea grandifolia were evaluated. All
      compounds caused some inhibition upon the aerial parts and root growth of the
      tested plants. The most active compound, 2-(4-formyl-2,5-dimethoxyphenyl)-5
      [(tridecyloxy)methyl]-benzo-1,4-quinone (12d), caused between 3 and 18%, and 12
      and 29% inhibition on the roots and aerial parts development of Cucumis sativus
      and Sorghum bicolor, respectively, and between 77 and 85%, and 34 and 52%
      inhibition on the roots and aerial parts growth of Euphorbia heterophylla and
      Ipomoea grandifolia, respectively.

PMID- 17193293
TI  - The influence of sawmill wood wastes on the distribution and population of
      macroinvertebrates at Benin River, Niger Delta area, Nigeria.
AB  - The impact of sawmill wood wastes on the distribution of benthic
      macroinvertebrates at the Sapele section of Benin River, Niger Delta, Nigeria,
      was investigated from March 2005 to August 2005. A total of 434 individuals were
      collected by kick-sampling method, representing 21 taxa of benthic
      macroinvertebrates. Three stations, 1, 2, and 3, were selected from upstream of
      the site, receiving wood wastes discharge, the impacted site and its down stream,
      respectively. Among the water quality variables, conductivity, dissolved oxygen,
      biochemical oxigen demand (BOD(5)), nitrate-nitrogen, phosphate-phosphorus,
      transparency, and alkalinity were significantly different (P<0.05) among the
      stations. Orthogonal comparison by Duncan's multiple range test showed that
      station 2 (the impacted site) was the cause of the difference. More sensitive
      species such as Ephemeroptera or Plecoptera were completely absent from station
      2, the impacted site. Species abundance was similar in station 1 and 3,
      indicating that the wood wastes must have adversely affected the distribution of
      these macroinvertebrates, especially the intolerant species. The wood waste
      discharge not only altered the water chemistry, but also stimulated the abundance
      of less-sensitive macroinvertebrate species.

PMID- 17193294
TI  - Peptaibiomics: Screening for polypeptide antibiotics (peptaibiotics) from plant
      protective Trichoderma species.
AB  - Eight strains of Trichoderma species (T. strigosum, T. erinaceus, T. pubescens,
      T. stromaticum, and T. spirale as well as T. cf. strigosum, T. cf. pubescens)
      were selected because of their antagonistic potential against Eutypa dieback and
      Esca which are fungal diseases of grapevine trunks. These isolates were screened
      for the production of a group of polypeptide antibiotics named peptaibiotics,
      including its subgroups peptaibols and lipopeptaibols. Fully-grown fungal
      cultures on potato-dextrose agar were extracted with CH(2)Cl(2)/MeOH, and these
      extracts were subjected to SPE using C(18) cartridges. The methanolic eluates
      were analyzed by on-line LC/ESI-MS(n) coupling--a method which is referred to as
      'peptaibiomics'. New seven-, ten-, and eleven-residue lipopeptaibols, with N
      terminal alkanoyl, and C-terminal leucinol or isoleucinol residues were found and
      named lipostrigocins and lipopubescins. Furthermore, new 18-residue peptaibols
      named trichostromaticins and 19-residue peptaibols named trichostrigocins were
      discovered. One peptaibiotic carrying a free C-terminal valine (or isovaline)
      named trichocompactin XII was also sequenced. These results corroborate the
      hypothesis that peptaibiotics might contribute to the plant-protective action of
      their fungal producers. The data also point out that comparison of peptaibiotic
      sequences is of limited relevance in order to establish chemotaxonomic
      relationships among species of the genus Trichoderma.

PMID- 17193295
TI  - The possible influence of L-histidine on the origin of the first peptides on the
      primordial Earth.
AB  - One of the most unsettled problems of prebiotic evolution and the origin of life
      is the explanation why one enantiomeric form of biomolecules prevailed. In the
      experiments presented in this paper, the influence of L-histidine on the peptide
      formation in the Salt-Induced Peptide Formation (SIPF) reaction of the
      enantiomeric forms of valine, proline, serine, lysine, and tryptophan, and the
      catalytic effects in this first step toward the first building blocks of proteins
      on the primordial earth were investigated. In the majority of the produced
      dipeptides, a remarkable increase of yields was shown, and the preference of the
      L-amino acids in the peptide formation in most cases cannot be denied. In
      summary, our data provide further experimental evidence for the plausibility of
      the SIPF reaction and point at a possible important role of L-histidine in the
      chemical evolution on the primordial Earth.

PMID- 17193296
TI  - Cluster analysis as selection and dereplication tool for the identification of
      new natural compounds from large sample sets.
AB  - Cluster analysis of gas-chromatographic (GC) data of ca. 500 bacterial isolates
      was used as an aid in detection and identification of new natural compounds. This
      approach reduces the number of GC/MS analysis (dereplication) and concomitantly
      improves the selection of samples with high probability to contain unknown
      natural products. Lipophilic bacterial extracts were derivatized and analyzed by
      GC under standardized conditions. A program was developed to convert
      chromatographic data into a two-dimensional matrix. Based on the results of
      hierarchical cluster analysis samples were selected for further investigation by
      GC/MS and NMR. This approach avoided unnecessary analysis of similar samples. By
      this method, the unusual oligoprenylsesquiterpenes 1 and 2 as well as new
      aromatic amides 7 and 8 were identified.

PMID- 17193297
TI  - Structure and vasorelaxant activity of floranol, a flavonoid isolated from the
      roots of Dioclea grandiflora.
AB  - The structure of the prenylated flavanonol, floranol (1=(2R,3R)-3,5,7-trihydroxy
      2-(2-hydroxyphenyl)-6-methoxy-8-(3-methylbut-2-enyl)-4H-1-benzopyran-4-one),
      isolated from the roots of Dioclea grandiflora (Fabaceae), was unambiguously
      determined by X-ray analysis. The compound was tested for vasorelaxant activity.
      In endothelium-containing aortic rings, floranol (1) induced a concentration
      dependent vasodilator effect in vessels precontracted with 0.1 microM
      phenylephrine with an IC(50) value of 19.9+/-2.4 microM. The removal of
      endothelium or pretreatment of vessels with the NO-synthase inhibitor L-NAME did
      not change the IC(50) and E(max) values for floranol-induced vasorelaxation. We
      conclude that floranol (1) should be acting directly in the rat-aorta smooth
      muscle cells to produce its vasorelaxant effect. The structure-activity
      relationship was discussed in terms of the 3-D floranol structure determined by X
      ray crystallography.

PMID- 17193298
TI  - Cytotoxic and new tetralone derivatives from Berchemia floribunda (Wall.) Brongn.
AB  - Two new alpha-tetralone (=3,4-dihydronaphthalen-1(2H)-one) derivatives,
      berchemiaside A and B (1 and 2, resp.), and one new flavonoid, quercetin-3-O-(2
      acetyl-alpha-L-arabinofuranoside (3), together with ten known flavonoids
      compounds, eriodictyol (4), aromadendrin (5), trans-dihydroquercetin (6), cis
      dihydroquercetin (7), kaempferol (8), kaempferol-3-O-alpha-L-arabinofuranoside
      (9), quercetin (10), quercetin-3-O-alpha-L-arabinofuranoside or avicularin (11),
      quercetin 3'-methyl ether, 3-O-alpha-L-arabinofuranoside (12), and maesopsin
      (13), were isolated from the bark of Berchemia floribunda. Their structures were
      determined by various NMR techniques and chemical studies. Compounds 3-13 were
      tested for their cytotoxic activity against human leukemia cells. Among them,
      kaempferol (8) and maesopsin (13) showed significant inhibitory activities
      against human leukemia cells CCRF-CEM and its multidrug-resistant sub-line,
      CEM/ADR5000, with IC(50) values of 14.0, 5.3, 10.2, and 12.3 microM,
      respectively.

PMID- 17193299
TI  - Synthesis and odor description of both enantiomers of methyl 4,5
      didehydrojasmonate, a component of jasmin absolute.
AB  - Synthesis of both enantiomers of methyl 4,5-didehydrojasmonate (1, Delta(4,5)
      MJA; >99.8% ee), a constituent of jasmin absolute, established the absolute
      configuration of the natural product, and their odor quality was evaluated. The
      fragrance of the natural (3S,7R)-enantiomer (a fresh natural, sweet floral fruity
      odor, reminiscent of Jasmin and Ylang Ylang flower, more intensive and tenacious)
      was superior to that of the unnatural (3R,7S)-enantiomer (a floral green odor
      with slight metallic green aspect, less intensive than the natural form) and the
      racemate (green-floral note, having weak and less volume than methyl jasmonate).
      Odor difference between natural and unnatural enantiomers of methyl jasmonate (2)
      is also reported.

PMID- 17193300
TI  - Chiral and achiral macrocyclic copper(II) complexes: Synthesis, characterization,
      and comparative binding studies with calf-thymus DNA.
AB  - The new chiral macrocyclic complexes [1,2-bis(1H-benzimidazol-2-yl)-1-(1,8
      dihydro-1,3,5,8,10,12-hexaazacyclotetradecane)-2-hydroxyethanolate] copper(II)
      and -nickel(II) perchlorate, 3 and 4, respectively, were synthesized by the
      reaction of 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol (L) and (1,8-dihydro
      1,3,5,8,10,12-hexaazacyclotetradecane)copper(II) and -nickel(II) diperchlorate
      complexes, 1 and 2, respectively. All complexes were characterized by various
      spectroscopic techniques. Molar-conductance measurements showed that all of the
      complexes are ionic in nature. In complexes 3 and 4, the metal center is
      encapsulated by the ligand L in a pentacoordinated environment. The optical
      rotation values ([alpha](D)) of 3 and 4 at 25 degrees indicate that the complexes
      are chiral. Absorption- and fluorescence-spectral studies, cyclic voltammetry,
      and viscosity measurements have been carried out to assess the comparative
      binding of complexes 1 and 3 with calf thymus (CT)-DNA. Analysis of the results
      suggests that the new chiral complex 3 binds to CT-DNA through a partial
      intercalation mode that is different from the binding mode of parent achiral
      complex 1. The complexes 1 and 3 bind to CT-DNA with binding constants K(b) of
      2.7 x 10(4) and 6.6 x 10(4) M(-1), respectively. Circular-dichroism (CD) studies
      have been further employed to ascertain the binding mode of complex 3, which is
      consistent with the other spectral studies.

PMID- 17193302
TI  - Proliferative activity of Echinacea angustifolia root extracts on cancer cells:
      Interference with doxorubicin cytotoxicity.
AB  - Doxorubicin is an anticancer drug that causes apoptosis in cells, but
      cardiotoxicity limits the cumulative dose that can remain in the blood. Echinacea
      extracts have been prescribed to supplement cancer chemotherapy. In a recent
      study, it was reported that Echinacea purpurea extracts protected noncancerous
      cells from apoptosis. Our study aimed to determine interference with doxorubicin
      chemotherapy, and if fractions and compounds from Echinacea angustifolia roots
      protected the cells. Cervical and breast cancer cells were treated with the
      Echinacea samples and doxorubicin. At 0.05 and 0.5 microM doxorubicin
      concentration, cynarine increased HeLa cell growth by 48-125% and 29-101%,
      respectively (p<0.01). At 0.05 microM doxorubicin concentration, chicoric acid
      increased cell growth by 23-100% (p<0.01). When MCF-7 cells were treated with
      Echinacea and doxorubicin, the ethyl acetate fraction increased cell growth by 20
      25%, and chicoric acid increased cell growth by 10-15%. Cynarine showed
      proliferative activity on HeLa cells, but showed antiproliferative activity on
      MCF-7 cells. Results indicate that phenolic compounds are responsible for
      proliferative activity. Studies with individual compounds show that chicoric acid
      and cynarine interfered with cells treated with 0.5 microM doxorubicin. The
      results of this study show that Echinacea herbal medicines affect cell
      proliferation despite cancer treatment, and that herbal medicines require further
      study with respect to anticancer drugs.

PMID- 17193301
TI  - Enzyme-mediated preparation of the enantiomerically enriched isomers of the
      odorous tetrahydropyranyl acetates Jasmal and Jessemal, and their olfactory
      evaluation.
AB  - All four stereoisomers of the fragrance Jasmal of structure 3,4,5,6-tetrahydro-3
      pentyl-2H-pyran-4-yl acetate were prepared by enzymatic resolutions of the
      corresponding alcohols. The absolute configurations were unambiguously determined
      by comparison with the enantiomer (3R,4S)-1 prepared from L-tartaric acid. The
      four stereoisomers of the fragrance Jessemal of structure 3-butyl-5-methyl
      3,4,5,6-tetrahydro-2H-pyran-4-yl acetate were obtained starting from the epoxy
      alcohol 10, which was obtained in an optically pure state by enzymatic resolution
      of the racemic mixture. The olfactory evaluations of all stereoisomers are
      reported. (1)H-NMR Conformational analysis of diastereoisomers (3RS,4RS,5RS)-2
      and (3RS,4SR,5RS)-2 is also reported.

PMID- 17193303
TI  - Petroleum industry effluents and other oxygen-demanding wastes in Niger Delta,
      Nigeria.
AB  - In this article, we review the fundamental phenomenon of oxygenation within the
      overriding context of petroleum-industry effluents and the other oxygen demanding
      wastes in Niger Delta, Nigeria. Drill cuttings, drilling mud (fluids used to
      stimulate the production processes), and accidental discharges of crude petroleum
      constitute serious land and water pollution in the oil-bearing province.
      Effluents from other industrial establishments such as distilleries, pulp and
      paper mills, fertilizer plants, and breweries, as well as thermal effluents,
      plant nutrients (such as nitrates and phosphates), and eroded sediments have also
      contributed to the pollution of their surrounding environment. Since these wastes
      are oxygen-demanding in nature, their impact on the recipient environment can be
      reversed by the direct application of simple chemistry. The wastes can be
      reduced, particularly in natural bodies of water, by direct oxidation-reduction
      processes or simple chemical combinations, acid-base reactions, and solubility
      equilibria; these are pH- and temperature-dependent. A shift in pH and alkalinity
      affects the solubility equilibria of Na+, Cl-, SO(2-), NO3(-), HCO3(-), and PO4(3
      ), and other ions and compounds.

PMID- 17193304
TI  - Ginsenoside Re and notoginsenoside R1: Immunologic adjuvants with low haemolytic
      effect.
AB  - The further purification of the total saponins from the roots of Panax
      notoginseng (Burk.) F. H. Chen by ordinary and reversed-phase silica-gel, as well
      as Sephadex LH-20 chromatography afforded two adjuvant active dammarane-type
      saponins, ginsenoside Re (1) and notoginsenoside R1 (2). These two saponins were
      evaluated for haemolytic activities and adjuvant potentials on the cellular and
      humoral immune responses of ICR mice against ovalbumin (OVA). The concentrations
      inducing 50% of the maximum haemolysis (HD50), using 0.5% red blood cell
      suspensions, were 469.6+/-16.9 and 420.4+/-22.9 microg/ml for 1 and 2,
      respectively. Compounds 1 and 2 significantly increased the concanavalin A (Con
      A)-, lipopolysaccharide (LPS)-, and OVA-induced splenocyte proliferation in the
      OVA-immunized mice (P<0.05, P<0.01, or P<0.001). The OVA-specific IgG, IgG1, and
      IgG2b antibody titres in serum were also significantly enhanced by 1 and 2
      compared with OVA control group (P<0.05, P<0.01, or P<0.001). The results
      indicate that 1 and 2 showed a slight haemolytic activity and significant
      adjuvant effect on specific antibody and cellular immune response against OVA in
      mice, and that the type of the terminal sugar of the sugar chain at C(6) of
      protopanaxatriol could not only affect their haemolytic activities and adjuvant
      potentials, but have significant effects on the nature of the immune responses.
      The information about this structure-function relationship might be useful for
      developing semisynthetic dammarane-type saponin derivatives with immunological
      adjuvant activity.

PMID- 17193305
TI  - The venomous secrets of the web droplets from the viscid spiral of the orb-weaver
      spider Nephila clavipes (Araneae, Tetragnatidae).
AB  - The capture web of N. clavipes presents viscous droplets, which play important
      roles in web mechanics and prey capture. By using scanning and transmission
      electron microscopy, it was demonstrated that the web droplets are constituted of
      different chemical environments, provided by the existence both of an aqueous and
      a lipid layer, which, in turn, present a suspension of tenths of vesicles
      containing polypeptides and/or lipids. GC/EI-MS Analysis of the contents of these
      vesicles led to the identification of some saturated fatty acids, such as
      decanoic acid, undecanoic acid, dodecanoic acid, tetradecanoic acid, octadecanoic
      acid, and icosanoic acid, while other components were unsaturated fatty acids,
      such as (Z)-tetradec-9-enoic acid, (Z)-octadec-9-enoic acid, and (Z)-icosa-11
      enoic acid; and polyunsaturated fatty acids like (9Z,12Z)-octadeca-9,12-dienoic
      acid, (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid, and (11Z,14Z)-icosa-11,14
      dienoic acid. Toxic proteins such as calcium-activated proteinase and
      metalloproteinase jararhagin-like precursor were also identified by using a
      proteomic approach, indicating the possible involvement of these enzymes in the
      pre-digestion of spiders' preys web-captured. Apparently, the mixture of fatty
      acids are relatively toxic to insects by topical application (LD50 64.3+/-7.6 ng
      mg(-1) honeybee), while the proteins alone present no topical effect; however,
      when injected into the prey-insects, these proteins presented a moderate toxicity
      (LD50 40.3+/-4.8 ng mg(-1) honeybee); the mixture of fatty acids and proteins is
      very toxic to the preys captured by the web droplets of the viscid spiral of
      Nephila clavipes when topically applied on them (LD50 14.3+/-1.8 ng mg(-1)
      honeybee).

PMID- 17193306
TI  - Induction of apoptosis in HeLa cells by 3beta-hydroxyurs-12-en-27-oic acid.
AB  - 3Beta-hydroxyurs-12-en-27-oic acid (1), a pentacyclic triterpenoid isolated from
      the rhizomes of Astilbe chinensis, was structurally very similar to ursolic acid,
      with the only difference being the interchange of the COOH and Me group at C(14)
      and C(17). Ursane-type triterpene with a COOH group at C(14) is present in a
      limited number of natural resources. Compound 1 was found to exhibit more
      distinctive cytotoxicity toward human cervical squamous carcinoma (HeLa) cells
      than ursolic acid, suggesting that the position of the COOH group significantly
      affects the cytotoxicity of ursane-type pentacyclic triterpenes with a COOH
      group. To elucidate the underlying biological mechanism responsible for the
      cytotoxicity of 1, we investigated its growth-inhibitory and apoptosis-inducing
      effect on HeLa cells. Compound 1 induced a marked concentration- and time
      dependent inhibition of cell proliferation with an IC50 value of 6.80+/-0.88
      microg/ml following 48 h incubation. The drug-treated HeLa cells displayed
      typical morphological apoptotic characteristics and formation of DNA ladders in
      agarose-gel electrophoresis. Flow cytometric analysis showed that the cell cycle
      was arrested in G0/G1 phase by 1, and the apoptotic rate of HeLa cells treated
      for 48 h with 20 microg/ml of 1 was 21.08+/-2.14%. Also, 1 increased and
      decreased the expression of Bax and Bcl-2 proteins, respectively, and lowered the
      mitochondrial transmembrane potential (delta psi(m)). The peptidic caspase-3
      inhibitor DEVD-CHO (NH2-Asp-Glu-Val-Asp-CHO, at 2 microM) could increase the
      viability of HeLa cells previously treated with 1. These results indicate that 1
      induces efficient cell apoptosis through down-regulating Bcl-2 expression, up
      regulating Bax expression, lowering delta psi(m), and by activating the caspase-3
      pathway.

PMID- 17193307
TI  - Immunosuppressive activity of the ethanol extract of Siegesbeckia orientalis on
      the immune responses to ovalbumin in mice.
AB  - The in vitro and in vivo immunosuppressive activity of the ethanol extract of
      Siegesbeckia orientalis (EESO) was studied on the immune responses in mice. EESO
      significantly suppressed concanavalin A (Con A)- and lipopolysaccharide (LPS)
      stimulated splenocyte proliferation in vitro in a concentration-dependent manner.
      ICR Mice were immunized subcutaneously with ovalbumin (OVA) on days 0 and 14.
      Beginning on the day of immunization, the mice were administered
      intraperitoneally with EESO at a single dose of 0.25, 0.5, and 1.0 mg at
      intervals of 7 days. On day 28, OVA-specific antibodies in serum, and mitogen-
      and OVA-induced splenocyte proliferation were measured. EESO significantly
      suppressed Con A-, LPS- and OVA-induced splenocyte proliferation in the OVA
      immunized mice in a dose-dependent manner. The OVA-specific serum IgG, IgG1, and
      IgG2b levels in the OVA-immunized mice were also significantly reduced by EESO.
      Moreover, reducing effect on the IgG1 antibody of EESO at the dose of 1.0 mg was
      more significant than that of cyclosporin A (CsA; positive drug). The results
      suggest that EESO could suppress the cellular and humoral response to ovalbumin
      in mice, and deserve further investigations to be developed as immunosuppressant.

PMID- 17193308
TI  - Five new iridoids from Patrinia rupestris.
AB  - Five new iridoids, namely rupesin A-E (1-5, resp.), together with six known
      iridoids, 6-11, were isolated from the roots of Patrinia rupestris. Their
      structures were elucidated by spectroscopic methods including IR, UV, MS, and 1D-
      and 2D-NMR experiments, and comparison with data of known analogues. Compounds 4
      and 11, compounds 1, 2, 5, 6, 8, 9, and 10, and compounds 3, 4, and 8 showed
      significant antibacterial activities against Bacillus subtilis, Escherichia coli,
      and Staphylococcus aureus, respectively.

PMID- 17193309
TI  - Nine new dammarane saponins from Gynostemma pentaphyllum.
AB  - Nine new dammarane saponins, 1-9, were isolated from the MeOH extract of the
      aerial part of Gynostemma pentaphyllum, an edible plant of the Cucurbitaceae
      family, that grows wildly in China. Their structures were elucidated by 1D- and
      2D-NMR analysis, as well as by chemical degradation. Aglycons 21,24
      cyclopentyldammar-25-ene of 6 and 7, and 21,24-cyclopentyldammarane of 8 and 9,
      were novel. Compounds 1, 4, and 8 showed moderate antitumor activities against
      stomach cancer cells SGC-7901 and liver cancer cells BEL-7402.

PMID- 17193310
TI  - New bisabolane sesquiterpenes and coumarin from Leontopodium longifolium.
AB  - From the roots of Leontopotium longifolium, three new bisabolane sesquiterpenes,
      rel-(1S,4R,5S,6R)-4,5-diacetoxy-6-[(R)-1,5-dimethylhexa-3,5-dienyl]-3
      methylcyclohex-2-enyl (Z)-2-methylbut-2-enoate (1), rel-(1S,4R,5S,6R)-4,5
      diacetoxy-6-[(R)-5-hydroxy-1,5-dimethylhex-3-enyl]-3-methylcyclohex-2-enyl (Z)-2
      methylbut-2-enoate (2), rel-(1R,2S,4R,5S)-4-acetoxy-2-[(R)-5-hydroxy-1,5
      dimethylhex-3-enyl]-5-methylcyclohexyl (Z)-2-methylbut-2-enoate (3), and a new
      coumarin, 2,3-dihydro-5-hydroxy-2-(1-methylethenyl)-7H-pyrano[2,3
      g][1,4]benzodioxin-7-one (4) together with nine known compounds have been
      isolated. The structures of these compounds were established by spectroscopic
      methods. Compounds 1 and 2 exhibited moderate cytotoxic activities against human
      promyelocytic leukemia (HL-60) cells.

PMID- 17193311
TI  - Four new compounds from the leaves of Acer truncatum.
AB  - Four new compounds, 3-(4-hydroxy-3,5-dimethoxyphenyl)propyl formate (1), 2,6
      dimethoxy-4-[(1S)-3-methoxypropyl]phenol (2), (1R,2R)-4-[(3R)-3-hydroxybutyl]
      3,3,5-trimethylcyclohex-4-ene-1,2-diol (3), and (1S,3R,3aR,6S,7S,9aR)-decahydro-1
      (hydroxymethyl)-1,7-dimethyl-3a,7-methano-3aH-cyclopentacyclooctene (4) were
      isolated from the leaves of Acer truncatum, together with twelve known compounds.
      Their structures were elucidated on the basis of extensive spectroscopic
      techniques. The absolute configuration of compound 3 was established by the
      modified Mosher's method. All compounds were evaluated for antibacterial
      activities.

PMID- 17193312
TI  - Iridoid glucosides and flavones from the aerial parts of Avicennia marina.
AB  - Two new iridoid glucosides, namely, 2'-O-[(2E,4E)-5-phenylpenta-2,4
      dienoyl]mussaenosidic acid (1; mussaenosidic acid = [1S
      (1alpha,4aalpha,7alpha,7aalpha)]-1-(beta-D-glucopyranosyloxy)-1,4a,5,6,7,7a
      hexahydro-7-hydroxy-7-methylcyclopenta[c]pyran-4-carboxylic acid) and 2'-O-(4
      methoxycinnamoyl)mussaenosidic acid (2), were isolated from the aerial parts of
      the mangrove plant Avicennia marina. Beside that, one known iridoid glucoside, 2'
      O-coumaroylmussaenosidic acid (3) and four known flavones (flavone = 2-phenyl-4H
      1-benzopyran-4-one) including 4',5-dihydroxy-3',7-dimethoxyflavone (4), 4',5
      dihydroxy-3',5',7-trimethoxyflavone (5), 4',5,7-trihydroxyflavone (6), and
      3',4',5-trihydroxy-7-methoxyflavone (7) were also isolated and identified. The
      structures of these compounds were elucidated by NMR spectroscopy and by low- and
      high-resolution mass spectrometry. The chemotaxonomic significance of these
      findings was discussed. In addition, each isolated compound was evaluated for the
      ability of alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical-scavenging
      activity.

PMID- 17193313
TI  - Cytotoxic sulfated triterpene glycosides from the sea cucumber Pseudocolochirus
      violaceus.
AB  - Bioassay-guided fractionation of the active BuOH extract of the sea cucumber
      Pseudocolochirus violaceus resulted in the isolation of three new sulfated
      triterpene glycosides, i.e., violaceusides I, II, and III (1-3, resp.), as active
      compounds causing morphological abnormality of Pyricularia oryzae mycelia. Their
      structures were elucidated by spectroscopic methods including 2D-NMR and MS
      experiments, as well as chemical evidence. Compounds 1-3 exhibit the same
      structural features, i.e., the presence of a 16-oxo group in the holostane-type
      triterpene aglycone with the C(7)=C(8) bond, but differ in the side chains and
      the tetrasaccharide moieties. Compound 1 possesses one sulfate group, while 2 and
      3 are disulfated glycosides. All the glycosides showed significant in vitro
      cytotoxicities against human gastric cancer MKN-45 and human colon cancer HCT-116
      cells.

PMID- 17193314
TI  - Anti-initiating activity of 3beta-methoxy-13alpha,14alpha-epoxyserratan-21beta-ol
      (PJJ-34) from the stem bark of Picea jezoensis Carr. var. jezoensis.
AB  - Ultraviolet light is the major cause of skin cancers in human, and several
      effects of ultraviolet light B (UVB) are thought to contribute to skin
      photocarcinogenesis. 3Beta-methoxy-13alpha,14alpha-epoxyserratan-21beta-ol (PJJ
      34; 1) isolated from Picea jezoensis Carr. var. jezoensis showed the strongest
      antitumor-promoting activity among naturally occurring triterpenoids in the in
      vivo two-stage mouse skin-carcinogenesis test. To investigate the anti-initiating
      activity, we further studied mouse models initiated with ultraviolet-B (UVB) and
      promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). Oral administration of
      the PJJ-34 (1) during a period before and after the three times of UVB
      irradiation led to a remarkable effect: oral administration of a 0.0025% solution
      of 1 only to the test group, which started one week before and ended one week
      after the irradiation, showed less than half papillomas, and inhibition of tumor
      incidence and tumor multiplicity in comparison to the control group. Therefore,
      it was recognized that PJJ-34 (1) showed strong anti-initiating activity as well
      as anti-promoting activity. After all, 1 seems to be useful as cancer
      chemopreventive agent.

PMID- 17193316
TI  - Investigation of de novo totally random biosequences, Part I: A general method
      for in vitro selection of folded domains from a random polypeptide library
      displayed on phage.
AB  - This paper reports the initial phase of a research aimed at investigating the
      folding frequency within a large library of polypeptides generated with a totally
      random sequence by phage-display technique. Resistance to proteolytic digestion
      has been used as a first, rudimentary folding criterion. The present paper
      describes, in particular, the development of a phage-display vector which has a
      selectable N-terminal affinity tag so that, after controlled proteolysis, the tag
      is cleaved from the phage. This enables the positive selection of phages that
      carry proteolytically resistant proteins. To test this system, avian pancreatic
      polypeptide (APP), one of the smallest proteins with a known structure, was
      chosen as a model, and its gene was inserted in a plasmid that was then used for
      phage display. A sequence of three amino acids, corresponding to a substrate for
      thrombin, was introduced at different locations within the APP sequence without
      significantly modifying the tertiary structure, as determined by circular
      dichroism (CD) analysis. These sequences were then used to show that the target
      tripeptide sequence was protected against proteolysis by the overall folding of
      the chain. Thus, these results show that the method permits the discrimination
      between folded and unfolded protein domains displayed on phage. The application
      of this protocol to a large library of totally random polypeptide chains is
      discussed as a preliminary to successive work, dealing with the production of
      totally random polypeptide sequences.

PMID- 17193317
TI  - Investigation of de novo totally random biosequences, Part II: On the folding
      frequency in a totally random library of de novo proteins obtained by phage
      display.
AB  - We present an investigation on theoretically possible protein structures which
      have not been selected by evolution and are, therefore, not present on our Earth
      ('Never Born Proteins' (NBP)). In particular, we attempt to assess whether and to
      what extent such polypeptides might be folded, thus acquiring a globular protein
      status. A library (ca. 10(9) clones) of totally random polypeptides, with a
      length of 50 amino acids, has been produced by phage display. The only structural
      bias in these sequences is a tripeptide substrate for thrombin: PRG, chosen
      according to the criteria described in the preceding Part I of this series. The
      presence of this substrate in an otherwise totally random sequence forms the
      basis for a qualitative experimental criterion which distinguishes unfolded from
      folded proteins, as folded proteins are more protected from protease digestion
      than unfolded ones. The investigation of 79 sequences, randomly selected from the
      initially large library, shows that over 20% of this population is thrombin
      resistant, likely due to folding. Analysis of the amino acid sequences of these
      clones shows no significant homology to extant proteins, which indicates that
      they are indeed totally de novo. A few of these sequences have been expressed,
      and here we describe the structural properties of two thrombin-resistant randomly
      selected ones. These two de novo proteins have been characterized by
      spectroscopic methods and, in particular, by circular dichroism. The data show a
      stable three-dimensional folding, which is temperature-resistant and can be
      reversibly denatured by urea. The consequences of this finding within a library
      of 'Never Born Proteins' are discussed in terms of molecular evolution.

PMID- 17193318
TI  - Investigation of de novo totally random biosequences, Part III: RNA Foster: A
      novel assay to investigate RNA folding structural properties.
AB  - Fold is essential to RNA properties, and, in particular, its thermodynamic
      stability can be used to monitor RNA-protein or RNA-ligand interactions, and to
      engineer RNA with novel or improved properties. While clearly valuable,
      experimental determination of RNA folding stability by traditional biophysical
      techniques requires substantial amounts of pure sample and rather expensive
      equipment. In this paper, we report a new, simple approach to the determination
      of RNA folding stability by coupling enzymatic digestion and temperature
      denaturation. The assay, named RNA folding stability Test (RNA Foster), is
      designed to probe the fraction of folded RNA (f(fold)) in an equilibrium mixture
      of folded and unfolded ones as a function of temperature. The simplicity of RNA
      Foster suggests that it can easily be scaled up for high-throughput studies of
      RNA folding stability both in basic and applied research.

PMID- 17193319
TI  - Investigation of de novo totally random biosequences, Part IV: Folding Properties
      of de novo, totally random RNAs.
AB  - This work lies within the framework of a broader project aimed at exploring the
      realm of all possible folded polypeptides; the main question addressed here is
      whether the corresponding RNAs also assume a folded conformation. We present an
      investigation on the structural properties of de novo, totally random RNAs by
      means of the 'RNA Foster' assay. Experimental results show that all RNAs studied
      are folded at 37 degrees , so that fold seems to be a common feature of RNAs.
      Random RNAs' fold shows a surprising thermal stability with an average T(m) value
      at ca. 50 degrees which prompts the idea that thermo-stable structures might not
      be as rare as they are commonly thought to be. The results are discussed within
      the general framework of random RNA properties such as those that might have been
      produced in a prebiotic scenario.

PMID- 17193320
TI  - Comparison of the biotransformation of the 14C-labelled insecticide carbaryl by
      non-transformed and human CYP1A1-, CYP1A2-, and CYP3A4-transgenic cell cultures
      of Nicotiana tabacum.
AB  - Transgenic tobacco-cell-suspension cultures expressing separately the human
      cytochrome P450 monooxygenases CYP1A1, CYP1A2, and CYP3A4 were utilized to study
      the biotransformation of the 14C-labelled insecticide carbaryl (=naphthalen-1-yl
      methylcarbamate). The resulting data were compared to similar data from the
      corresponding non-transformed (NT) tobacco-cell culture and commercially
      available membrane preparations (Bactosomes) of genetically modified bacteria
      separately containing the same human P450s. A rapid conversion rate of carbaryl
      was observed with the CYP1A1 and CYP1A2 cells, where only 49.7 and 0.2% of
      applied carbaryl (1 mg/l), respectively, remained after 24 h, as compared to
      77.7% in the non-transformed culture. Unexpectedly, the corresponding results
      obtained from the CYP3A4 cultures were not definite. With 25 mg/l of carbaryl and
      96 h of incubation, it was proven that the insecticide is also substrate of
      CYP3A4. This finding was supported by GC/EI-MS analysis of the primary metabolite
      pattern produced by the isozyme. This consisted of naphthalene-1-ol, N
      (hydroxymethyl)carbaryl, 4-hydroxycarbaryl, and 5-hydroxycarbaryl, whereas the
      main product in non-transformed cells was N-(hydroxymethyl)carbaryl. Data
      obtained from the CYP1A1, CYP1A2, or CYP3A4 Bactosomes agreed with those of the
      P450-transgenic tobacco cells. Problems with GC/EI-MS analysis of carbaryl and
      its metabolites are discussed.

PMID- 17193321
TI  - Relationships between inhibitory activity against a cancer cell line panel,
      profiles of plants collected, and compound classes isolated in an anticancer drug
      discovery project.
AB  - In an attempt to determine the relationships between the plant profiles (country
      of collection, taxonomy, plant part) and the compound classes isolated with
      cytotoxic activity against a panel of human tumor cell lines, the data compiled
      from a 15-year anticancer drug-discovery project were subjected to an analysis of
      variance (ANOVA). The results indicate significant trends in cytotoxic activity
      relative to collection location, taxonomy, plant part, and compound classes
      isolated. Plant collections were made in tropical forests in six countries, with
      collections from Ecuador resulting in higher activity than those from Indonesia
      and Peru. Interestingly, collections from Florida were not statistically
      different than those from the countries with higher biodiversity. One hundred and
      forty-five families were represented in the collections, with the Clusiaceae,
      Elaeocarpaceae, Meliaceae, and Rubiaceae having low ED50 (half maximal effective
      dose) values. Especially active genera included Aglaia, Casearia, Exostema,
      Mallotus, and Trichosanthes. Roots and below-ground plant materials were
      significantly more active than above-ground materials. Cucurbitacins,
      flavaglines, anthraquinones, fatty acids, tropane alkaloids, lignans, and
      sesquiterpenoids were significantly more active than xanthones and
      oligorhamnosides. The results from this study should serve as a guide for future
      plant collection endeavors for anticancer drug discovery.

PMID- 17193322
TI  - Novel rearranged abietane diterpenoids from the roots of Salvia sahendica.
AB  - Two naphthoquinone diterpenoids, 1 and 2, one tricyclic, and one tetracyclic
      rearranged abietane ('4,5-seco-10,5-friedo-abietane') diterpenoids, 3 and 4,
      respectively, together with horminone (5) have been isolated from the roots of
      Salvia sahendica. Compounds 2 and 3 are new, and the 13C-NMR assignment for
      compound 4 was modified using ' Heteronuclear Multiple-Bond Correlation' (HMBC)
      spectroscopic data. The structures of the compounds have been established by
      using different spectral data including 1D- and 2D-NMR, IR, UV, and MS. The
      elemental composition for the major peaks of 3 and 4 were determined by ' High
      Resolution Electron Impact Mass Spectrometry' (HR-EI-MS). The relative
      configurations of the new compounds were determined by 1H-NMR and 'Rotating-Frame
      NOES' (ROESY) spectroscopy. Compounds 1, 2, and 5 showed antifungal activities
      when tested on Blakeslea trispora. Lapachol, a prelynated naphthoquinone, was
      used as a positive control. The biological activities of the related
      naphthoquinones and abietane diterpenoids were discussed.

PMID- 17193323
TI  - Antitrypanosomal cycloartane glycosides from Astragalus baibutensis.
AB  - Baibutoside (5), a new cycloartane-type triterpene glycoside, has been isolated
      from the roots of Astragalus baibutensis along with four known glycosides,
      acetylastragaloside I (1), and astragalosides I, II, and IV (2-4, resp.). The
      structure elucidation of the compounds were achieved by a combination of one- and
      two-dimensional NMR techniques (DQF-COSY, HSQC, HMBC, and ROESY), and mass
      spectrometry (ESI-MS), where all the compounds were shown to have cycloastragenol
      (=(20R,24S)-3beta,6alpha,16beta,25-tetrahydroxy-20,24-epoxy-9,19-cyclolanostane)
      as aglycone. All compounds were tested for in vitro antiprotozoal activity.
      Compounds 1-4 displayed notable activity vs. Trypanosoma brucei rhodesiense, with
      acetylastragaloside I (1) being the most potent (IC50 9.5 microg/ml).
      Acetylastragaloside I (1) was also lethal to T. cruzi (IC50 5.0 microg/ml), and
      it is the first cycloartane-type triterpene with remarkable trypanocidal activity
      against both T. brucei rhodesiense and T. cruzi. However, it exhibits some
      cytotoxicity on mammalian cells.

PMID- 17193325
TI  - Total synthesis and biological evaluation of (-)-pectinatone employing a methyl
      branched wax ester as key building block.
AB  - Unnatural (-)-pectinatone ((-)-3) was prepared in five steps starting from the
      highly methyl-branched wax ester 4, employing bromination of the ester enolate
      and subsequent base-induced elimination to the enoate 6 as the key step. Both (-)
      3 and the amides 8b and 8c, which were isolated as by-products in the reaction
      sequence, displayed antimicrobial activity and cytotoxicity.

PMID- 17193324
TI  - Two new tetracyclic triterpenes from the heartwood of Ailanthus excelsa Roxb.
AB  - Two new dammarane-type triterpenes, ailexcelone and ailexcelol, together with
      ocotillone, malabaricol, epoxymalabaricol, lupeol, and sitosterol-3-O-beta-D
      glucoside were isolated from the heartwood of Ailanthus excelsa. The structures
      of the new compounds were established on the basis of 1D- and 2D-NMR data.
      Ocotillone, malabaricol and epoxymalabaricol were isolated for the first time
      from A. excelsa. All of the isolates were tested for their antifungal activity.

PMID- 17193326
TI  - Combinatorial synthesis by nature: volatile organic sulfur-containing
      constituents of Ruta chalepensis L.
AB  - Ongoing interest in discovering new natural fragrance and flavor ingredients
      prompted us to examine a solvent extract of sulfurous-sweaty smelling Ruta
      chalepensis L. (Rutaceae) plant material more closely. Twenty-one sulfur
      containing constituents of similar structures were identified by GC/MS
      techniques. Amongst them, 14 have never been described to occur in nature. The
      compounds 1-18 belong to a family of natural flavor and fragrance molecules
      having a 1,3-positioned O,S moiety in common. The identities of the natural
      constituents were confirmed by comparison with synthetic reference samples, and
      the organoleptic properties of the latter were studied. The relative and absolute
      configurations of the four stereoisomers of 4-methyl-3-sulfanylhexan-1-ol (5)
      were established by stereoselective synthesis. The natural isomers consisted of a
      65 : 35 mixture of (3R,4S)-5 and (3S,4S)-5.

PMID- 17193328
TI  - Immunosuppressive activity of Semen Persicae ethanol extract on specific antibody
      and cellular response to ovalbumin in mice.
AB  - The immunosuppressive activity of the ethanol extract of Semen Persicae (EESP)
      was studied with respect to specific antibody and cellular response to ovalbumin
      (OVA) in mice. The effects of EESP on mice splenocyte proliferation in vitro were
      measured. EESP significantly suppressed concanavalin A (ConA)- and
      lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro in a
      concentration-dependent manner. Furthermore, the effects of EESP at three dose
      levels on the humoral and cellular immune responses in the OVA-immunized mice
      were examined. ICR Mice were immunized subcutaneously with OVA on day 0 and 14.
      Starting on the day of immunization, the mice were administered intraperitoneally
      with EESP at a single dose of 0.25, 0.5, and 1.0 mg, and cyclosporin A (CsA,
      positive drug) at a single dose of 0.1 mg at intervals of 7 days. On day 28,
      mitogen- and OVA-induced splenocyte proliferation and OVA-specific antibody level
      in serum were measured. EESP significantly decreased ConA-, LPS-, and OVA-induced
      splenocyte proliferation in the OVA-immunized mice at the dose of 1.0 mg.
      Meanwhile, the OVA-specific serum IgG, IgG1, and IgG2b antibody levels in the OVA
      immunized mice were markedly reduced by EESP in a dose-dependent manner. The
      results suggest that EESP could suppress the cellular and humoral immune response
      in mice, and deserve further research to be developed as immunosuppressant.

PMID- 17193327
TI  - The oxidative damage of plasmid DNA by ascorbic acid derivatives in vitro: the
      first research on the relationship between the structure of ascorbic acid and the
      oxidative damage of plasmid DNA.
AB  - To study the structure-function relationship of the oxidative-damage effect of
      ascorbic acid, we have focused on the interaction between plasmid DNA pUC19 and a
      series of ascorbic acid derivatives modified on different OH groups in the
      presence of transition metal ions. Some ascorbic acid derivatives can selectively
      cleave plasmid DNA from Form I to Form II in the presence of low concentration of
      Cu2+ just like ascorbic acid itself, while other derivatives oxidatively damage
      plasmid DNA slightly. We found that those derivatives with unattached 2-OH and 3
      OH groups retain the ability to cleave the plasmid DNA. The derivatives that have
      been methylated on 2-OH or 3-OH can only cleave plasmid DNA softly, and those
      derivatives that have been protected on both 2-OH and 3-OH can hardly exert an
      oxidative damage on plasmid DNA under the same condition. Form these results, we
      can draw the conclusion that 2-OH and 3-OH groups of the ascorbic acid molecule
      contribute most to this biological activity.

PMID- 17193329
TI  - Synthesis and cytotoxic evaluation of a series of resveratrol derivatives.
AB  - A total of 17 resveratrol (=(E)-5-[2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol)
      derivatives were synthesized from resveratrol (RES) through a facile approach.
      Among them, 13 compounds, 2 and 6-17, were reported for the first time, while 1
      and 3-5 had already been reported several years ago. The cytotoxic activities of
      these compounds were evaluated against human nasopharyngeal epidermoid tumor cell
      line KB, and compounds 1 and 8-11 showed strong anticancer activities in vitro,
      comparable with that of 5-fluorouracil, an anticancer drug. On the basis of the
      experimental data obtained, structure-activity relationships are discussed.

PMID- 17193330
TI  - N1,N5,N10-Tris(4-hydroxycinnamoyl)spermidines from Microdesmis keayana roots.
AB  - Three new N1,N5,N10-tris(4-hydroxycinnamoyl)spermidines were isolated from a
      methanolic root extract of Microdesmis keayana. They were identified as N5,N10
      di(p-coumaroyl)-N1-feruloylspermidine,N5-(p-coumaroyl)-N1,N10
      diferuloylspermidine, and N1,N5,N10-triferuloylspermidine, and were named
      keayanidines A, B, and C (1-3), respectively. Their structures were established
      by spectral techniques(electrospray mass spectrometry, one- and two-dimensional
      NMR). A 4',4'',4'''-trimethylated derivative was prepared by methylation of
      keayanidine C, and the same compound was synthesized fromspermidine and 3,4
      dimethoxycinnamic acid to confirm the spectral attributions of the NMR data of
      the natural compounds. Radical-scavenging properties of all compounds were
      evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical spectrophotometric
      assay.

PMID- 17193331
TI  - Benzophenanthridine alkaloids from Zanthoxylum nitidum (Roxb.) DC, and their
      analgesic and anti-inflammatory activities.
AB  - Seven benzophenanthridine alkaloids, 1-7, were isolated from the roots of
      Zanthoxylum nitidum. Among them, two novel alkaloids, named (R)-8-[(R)-1
      hydroxyethyl]dihydrochelerythrine (1) and 8-methoxynorchelerythrine (2), were
      structurally identified as new compounds on the basis of the spectroscopic
      analysis. Bioactivity evaluation showed that nitidine (3), dihydrochelerythrine
      (4), oxyavicine (5), 8-methoxychelerythrine (6), and 8
      hydroxydihydrochelerythrine (7) exhibit comparable analgesic and anti
      inflammatory effects as hydrocortisone.

PMID- 17193332
TI  - Isolation of four new pterocarpans from Zygophyllum eurypterum (Syn. Z.
      atriplicoides) with enzyme-inhibition properties.
AB  - Four new pterocarpans, atricarpan A (=(-)-1,2-dihydroxy-4-(hydroxymethyl)-3,9
      dimethoxypterocarpan; 1), atricarpan B (=(-)-2,3-ethylenedioxy)-1,4-dihydroxy-9
      methoxypterocarpan; 2), atricarpan C (=(-)-1,9-dimethoxypterocarpan-3-carboxylic
      acid; 3), and atricarpan D (=(-)-2,9-dimethoxy-4-(5-oxohexyl)pterocarpan; 4) were
      isolated from the BuOH extract of the whole plant of Zygophyllum eurypterum. The
      structure elucidations of those compounds were based primarily on 1D- and 2D-NMR
      analysis, including COSY, HMBC, and HMQC correlations. Compounds 1-4 also
      inhibited butyrylcholinesterase (BChE; EC 3.1.1.8) enzyme in a concentration
      dependent manner with IC(50) values between 12.5-65.0 microM. Similarly,
      compounds 1 and 4 inhibited lipoxygenase (LOX; EC 1.13.11.12) and
      acetylcholinesterase (AChE; EC 3.1.1.7) enzymes with IC50 values of 13.5 and 20.5
      muM, respectively.

PMID- 17193333
TI  - Cyclodextrins found in enzyme- and heat-processed starch-containing foods.
AB  - Native and branched-type (glucosylated and maltosylated) cyclodextrins have been
      isolated and identified in different enzyme- and heat-processed starch-containing
      food products. Amylolytic enzyme-processed foods such as different beer samples,
      corn syrup of different dextrose equivalents, and thermally-processed food such
      as bread, contained minute amounts of different types of cyclodextrins. HPLC/MS
      Analyses of appropriately preconcentrated and purified food samples indicated the
      presence of parent beta- and gamma-cyclodextrins and all the three, alpha-, beta
      , and gamma-branched cyclodextrins with different degrees of glycosylation. The
      data presented in this account are thought to be of practical importance in terms
      of both the analysis methods used for the cyclodextrins and the approval status
      of different cyclodextrin-containing food, cosmetic, and pharmaceutical products.

PMID- 17193334
TI  - Male cephalic labial gland secretions of two bumblebee species of the subgenus
      Cullumanobombus (Hymenoptera: Apidae: Bombus latreille) and their distribution in
      central Europe.
AB  - The cephalic labial gland secretion of Bombus semenoviellus males was analyzed,
      and its chemical composition is reported for the first time. The secretion
      functions as sex or marking pheromone. Eighty compounds were identified in the
      secretion, the main one being all-trans-geranylgeranyl acetate (48%). The same
      compound was shown to form 87% of the labial gland secretion of B. cullumanus
      males. Both species are closely related and belong to the subgenus
      Cullumanobombus.

PMID- 17193335
TI  - New glycosides from Tetracentron sinense and their cytotoxic activity.
AB  - One novel neolignan (tetracentronsine; 1), one new indole alkaloid (=3-(2
      hydroxyethyl)-1H-indole-5-O-beta-D-glucopyranoside; 2), and two new phenol
      derivatives, 3-{2-[(beta-glucopyranosyl)oxy]-4,5-(methylenedioxy)phenyl}propanoic
      acid (3) and methyl 3-{2-[(beta-glucopyranosyl)oxy]-4,5
      (methylenedioxy)phenyl}propanoate (4), together with six known compounds were
      isolated from the stem bark of Tetracentron sinense. Their structures were
      determined by spectral analysis, including 1D- and 2D-NMR, and MS analyses. These
      compounds were tested for their cytotoxic activity against human leukaemia cells
      in vitro. Among them, compound 2, (E)-3-(4-hydroxyphenyl)-N-[2-(4
      hydroxyphenyl)ethyl]prop-2-enamide (5), and maslinic acid (6) showed significant
      inhibitory activities against human leukaemia cells CCRF-CEM and its multidrug
      resistant sub-line, CEM/ADR5000, with IC50 values in a range of 7.1 to 29.7
      microM.

PMID- 17193336
TI  - Cytotoxic ent-kauranoids from Isodon parvifolius.
AB  - Three new ent-kaurane diterpenoids, parvifoline Z (1), parvifoline AA (2), and
      parvifoline AB (3), together with 14 known compounds, were isolated from the
      leaves of Isodon parvifolius. The structures of the new compounds were elucidated
      by 1D- and 2D-NMR spectroscopy and mass spectrometry, and by comparison with
      known compounds. These three new diterpenoids included three types of ent
      kauranoids, namely, C(20)-non-oxygenated-ent-kauranoid, 7,20-cyclo-ent-kauranoid
      and 6,7-seco-ent-kauranoid-7,20-olide. Compounds 1 and 2 exhibited significant
      cytotoxicities against A549, HT-29, and K562 cell lines.

PMID- 17193337
TI  - New cholinesterase-inhibiting triterpenoid alkaloids from Buxus hyrcana.
AB  - The current phytochemical investigation on Buxus hyrcana Pojark. has resulted in
      the isolation of the triterpenoid alkaloids 1-10. The structures of five new
      alkaloids, hyrcanone (1), hyrcanol (2), hyrcatrienine (3), N(b)
      dimethylcycloxobuxoviricine (4), and hyrcamine (5), were elucidated by means of
      modern spectroscopic techniques, while the known alkaloids, buxidin (6),
      buxandrine (7), buxabenzacinine (8), buxippine-K (9) and E-buxenone (10), were
      identified by comparing their spectral data with those reported earlier.
      Compounds 1 and 3-9 were found to be acetyl- and butyrylcholinesterase
      inhibitors. The IC50 values were estimated to be in the range of 83.0-468.0
      microM against AChE and 1.12-350.0 microM against BChE. The structure-activity
      relationship studies suggested that the presence of dimethylamino moieties at
      C(3) and C(20) is the most important factor influencing the activity of these
      compounds against the cholinesterase enzymes. All compounds were also evaluated
      for cytotoxicity on a fibroblast cell line with incubation of 24 h. No cytotoxic
      effects were exerted by any compound.

PMID- 17193340
TI  - Utility of the Algase Wandering Scale in an outpatient Alzheimer's disease
      sample.
AB  - BACKGROUND: Wandering represents a major problem in the management of patients
      with Alzheimer's disease (AD). In this study we examined the utility of the
      Algase Wandering Scale (AWS), a newly developed psychometric instrument that asks
      caregivers to assess the likelihood of wandering behavior. METHODS: The AWS was
      administered to the caregivers of 40 AD patients and total and subscale scores
      were examined in relation to measures of mental and functional status, depressive
      symptoms and medication usage. RESULTS: AWS scores were comparable, though
      slightly lower, than those normative values previously published. Higher scores
      were associated with more severe dementia. The Negative Outcome subscale showed a
      significant increase in reported falls or injuries in association with anti
      depressant use. CONCLUSIONS: These data provide some construct validation for the
      AWS as a potentially useful scale to assess wandering behaviors in AD.

PMID- 17193341
TI  - The prevalence of psychiatric symptoms and behavioural disturbances and the use
      of psychotropic drugs in Norwegian nursing homes.
AB  - BACKGROUND: Psychiatric and behavioural symptoms in dementia are associated with
      a range of negative outcomes, including institutional placement and the
      widespread use of psychotropic drugs in spite of limited evidence for their
      efficacy. AIMS: To determine the prevalence of psychiatric and behavioural
      symptoms and the pattern of psychotropic drug prescription in patients with
      various degrees of dementia. METHODS: A sample of 1,163 non-selected nursing home
      patients were assessed by means of the Neuropsychiatric Inventory, the Clinical
      Dementia Rating scale and Lawton's activities of daily living scale. In addition,
      information was collected from the patients' records. RESULTS: Dementia was found
      in 81% of the patients and 72% of them had clinically significant psychiatric and
      behavioural symptoms. The frequencies of symptoms increased with the severity of
      the dementia. Psychotropic medication was being prescribed to 75% of patients
      with dementia. There was a significant relationship between the type of drug and
      the symptom for which it had been dispensed. CONCLUSION: Psychiatric and
      behavioural symptoms are frequent in nursing homes and the rate increases with
      the progression of the dementia. Systematic programmes are needed for
      disseminating skills and providing guidance regarding the evaluation and
      treatment of these symptoms in nursing homes.

PMID- 17193343
TI  - The beginning of a small revolution.

PMID- 17193345
TI  - "There is plenty of room at the bottom for innovation": a report on "Nano2004",
      the 7th International Conference on Nanostructured Materials.

PMID- 17193346
TI  - Optical switching of hierarchical self-assembly: towards "enlightened" materials.

PMID- 17193347
TI  - Tailor-made nanoparticles via gas-phase synthesis.
AB  - Gas-phase synthesis is a well-known chemical manufacturing technique for an
      extensive variety of nanoscale particles. Since the potential of ultrafine and,
      in particular, nanoscale particles in high-performance applications has been
      identified, scientific and commercial interest has increased immensely, thus
      identifying this field as a most important technology of the future. However,
      nanomaterials can perform their multifunctional tasks only if they are customized
      in terms of chemical composition, size, and morphology to suit the application at
      hand. Profound knowledge of the synthesis and precise process control is crucial
      in meeting the stringent specifications. Although the gas-phase synthesis of
      ultrafine materials has been known and commercially exploited for decades,
      existing knowledge is based almost exclusively on empirical know-how. Process
      simulation is a very suitable tool for expanding the understanding of the
      synthesis-relevant processes, particle formation mechanisms, and operating
      parameters. Based on the resulting expertise some special nanoscale gas-phase
      products of high innovative potential have been developed.

PMID- 17193348
TI  - On the development of colloidal nanoparticles towards multifunctional structures
      and their possible use for biological applications.
AB  - In this Review, we describe the synthesis of high-quality colloidal nanoparticles
      in organic solvents, the mechanisms by which they can be transferred into aqueous
      solution, and some of their applications in biology. In particular, we will place
      emphasis on the creation of multifunctional nanoparticles or nanoparticle
      assemblies.

PMID- 17193349
TI  - Top-down meets bottom-up: dip-pen nanolithography and DNA-directed assembly of
      nanoscale electrical circuits.

PMID- 17193350
TI  - Nanowell-array surfaces.

PMID- 17193351
TI  - The behavior of Au55 nanoclusters on and in thiol-terminated dendrimer
      monolayers.

PMID- 17193352
TI  - Beyond the herringbone reconstruction: magic gold fingers.

PMID- 17193353
TI  - Layered organosilicate nanoparticles with liquidlike behavior.

PMID- 17193354
TI  - Use of electrospinning to directly fabricate hollow nanofibers with
      functionalized inner and outer surfaces.

PMID- 17193355
TI  - Powering a supramolecular machine with a photoactive molecular triad.

PMID- 17193356
TI  - InN nanocrystals, nanowires, and nanotubes.

PMID- 17193357
TI  - Sn-catalyzed thermal evaporation synthesis of tetrapod-branched ZnSe nanorod
      architectures.

PMID- 17193358
TI  - Formation of dendrimer nanotubes by layer-by-layer deposition.

PMID- 17193360
TI  - Wet-chemical assembly of carbon tube-in-tube nanostructures.

PMID- 17193359
TI  - DNA-driven assembly of mesoporous silica/gold satellite nanostructures.

PMID- 17193361
TI  - Synthesis of yttria-based crystalline and lamellar nanostructures and their
      formation mechanism.
AB  - A nonaqueous synthetic route for the preparation of a regular crystalline yttria
      mesostructure is presented. The reaction between yttrium alkoxides and benzyl
      alcohol results in the formation of a highly ordered lamellar nanocomposite
      consisting of yttria layers with a confined thickness of about 0.6 nm, separated
      from each other by organic layers of intercalated benzoate molecules. Doping with
      europium leads to strong red luminescence. The nanostructure formation proceeds
      via two reactions. A C--C bond formation occurs between benzyl alcohol and the
      isopropanolate ligand. At the same time, yttrium oxide catalyzes two low
      temperature hydride-transfer reactions to form benzoic acid and toluene from
      benzyl alcohol via benzaldehyde, thus limiting the growth of the thickness of the
      lamellae.

PMID- 17193363
TI  - 2D self-assembly of oligo(p-phenylene vinylene) derivatives: from dimers to
      chiral rosettes.
AB  - Enantiomerically pure oligo(p-phenylene vinylene) diaminotriazine derivatives and
      a short structurally related achiral diaminotriazine derivative, all having a
      rigid backbone in common, are studied to self-assemble at the solution-graphite
      interface by scanning tunneling microscopy. As a function of the length of the
      backbone, different two-dimensional motifs are formed (dimers and rosettes) that
      are rationalized in terms of the balance between different intermolecular
      interactions, in this case, intermolecular hydrogen bonding and the packing
      requirements of the alkyl chains on a graphite surface. In addition, the effect
      of molecular chirality on monolayer chirality is investigated, revealing
      molecular size-dependent expressions of the monolayer chirality.

PMID- 17193362
TI  - Optical properties of nanoparticle-based metallodielectric inverse opals.
AB  - Metallodielectric inverse opals were prepared by co-crystallizing silica-coated
      gold nanoparticles and polymer spheres, followed by removal of the crystal
      template. The inverse opals exhibit a distinct reflectance peak, which results
      from Bragg diffraction due to the highly ordered 3D macroporous structure.
      Photonic band-structure calculations indicate that the characteristic reflectance
      peaks observed are signatures of the directional gap at the L point. It is
      demonstrated that the optical properties (the position and magnitude of the
      electromagnetic bandgaps) of the gold-silica nanocomposite inverse opals can be
      engineered by varying the nanoparticle morphology (core size and shell thickness)
      and/or the nanoparticle volume-filling ratio of the composite. The use of
      metallodielectric nanoparticles to form inverse opals offers a versatile approach
      to prepare photonic materials that may exhibit absolute bandgaps.

PMID- 17193364
TI  - Suspended carbon nanotube quantum wires with two gates.
AB  - Suspended single-walled carbon nanotube devices comprised of high-quality
      electrical contacts and two electrostatic gates per device have been prepared.
      Compared to nanotubes pinned on substrates, the suspended devices exhibit little
      hysteresis related to environmental factors and act as cleaner Fabry-Perot
      interferometers or single-electron transistors. The high-field saturation
      currents in the suspended nanotubes related to optical phonon or zone-boundary
      phonon scattering are significantly lower due to the lack of efficient heat
      sinking. The multiple-gate design may also facilitate future investigations into
      the electromechanical properties of nanotube quantum systems.

PMID- 17193365
TI  - Nanowires for integrated multicolor nanophotonics.
AB  - Nanoscale light-emitting diodes (nanoLEDs) with colors spanning from the
      ultraviolet to near-infrared region of the electromagnetic spectrum were prepared
      using a solution-based approach in which emissive electron-doped semiconductor
      nanowires were assembled with nonemissive hole-doped silicon nanowires in a
      crossed nanowire architecture. Single- and multicolor nanoLED devices and arrays
      were made with colors specified in a predictable way by the bandgaps of the III-V
      and II-VI nanowire building blocks. The approach was extended to combine
      nanoscale electronic and photonic devices into integrated structures, where a
      nanoscale transistor was used to switch the nanoLED on and off. In addition, this
      approach was generalized to hybrid devices consisting of nanowire emitters
      assembled on lithographically patterned planar silicon structures, which could
      provide a route for integrating photonic devices with conventional silicon
      microelectronics. Lastly, nanoLEDs were used to optically excite emissive
      molecules and nanoclusters, and hence could enable a range of integrated
      sensor/detection "chips" with multiplexed analysis capabilities.

PMID- 17193370
TI  - The problem of purifying single-walled carbon nanotubes.

PMID- 17193371
TI  - Recent developments in nanofabrication using focused ion beams.
AB  - Focused ion beam (FIB) technology has become increasingly popular in the
      fabrication of nanoscale structures. In this paper, the recent developments of
      the FIB technology are examined with emphasis on its ability to fabricate a wide
      variety of nanostructures. FIB-based nanofabrication involves four major
      approaches: milling, implantation, ion-induced deposition, and ion-assisted
      etching of materials; all these approaches are reviewed separately. Following an
      introduction of the uniqueness and strength of the technology, the ion source and
      systems used for FIB are presented. The principle and specific techniques
      underlying each of the four approaches are subsequently studied with emphasis on
      their abilities of writing structures with nanoscale accuracy. The differences
      and uniqueness among these techniques are also discussed. Finally, concluding
      remarks are provided where the strength and weakness of the techniques studied
      are summarized and the scopes for technological improvement and future research
      are recommended.

PMID- 17193373
TI  - High-yield synthesis of single-crystal nanosprings of ZnO.

PMID- 17193372
TI  - Sub-100 nm, centimeter-scale, parallel dip-pen nanolithography.

PMID- 17193374
TI  - Synthesis and characterization of thiol-capped FePt nanomagnetic porous
      particles.

PMID- 17193375
TI  - Cutting single-walled carbon nanotubes with an electron beam: evidence for atom
      migration inside nanotubes.

PMID- 17193376
TI  - Flexible ultraviolet random lasers based on nanoparticles.

PMID- 17193377
TI  - No platelet can adhere--largely improved blood compatibility on nanostructured
      superhydrophobic surfaces.

PMID- 17193378
TI  - From self-assembly of platinum nanoparticles to nanostructured materials.

PMID- 17193379
TI  - Highly improved green photoluminescence from CePO4:Tb/LaPO4 core/shell nanowires.

PMID- 17193380
TI  - Ionic-electronic conductor nanostructures: template-confined growth and nonlinear
      electrical transport.

PMID- 17193381
TI  - Spontaneous formation of transition-metal nanoparticles on single-walled carbon
      nanotubes anchored with conjugated molecules.

PMID- 17193382
TI  - Optical waveguide through CdS nanoribbons.

PMID- 17193383
TI  - Alignment and assembly of adsorbed collagen molecules induced by anisotropic
      chemical nanopatterns.
AB  - Collagen, a protein widely used to control cell-material interactions, is known
      to self-assemble in solution. Supramolecular structures also form on material
      surfaces following collagen adsorption. Herein, we report the use of anisotropic,
      flat, surface chemical nanopatterns, which consist of alkyl-terminated tracks
      drawn in an oligo(ethylene glycol)-terminated matrix, to direct collagen
      adsorption. As revealed by atomic force microscopy, the spontaneous collagen
      adsorption performed on such patterned substrates results in the accumulation of
      collagen on the hydrophobic tracks. Moreover, the width of the tracks (30-90 nm),
      which is much smaller than the length of the collagen molecule (approximately 300
      nm), is the origin of preferential alignment of the molecules and of their
      assembly into continuous bundles of adsorbed collagen. This chemical guidance
      effect due to self-confinement of proteins upon adsorption may bring novel and
      valuable applications, specifically in biomaterials science and cell growth
      control.

PMID- 17193384
TI  - Biomimetic micropatterning of silica by surface-initiated polymerization and
      microcontact printing.
AB  - Micropatterns of silica on a gold substrate were generated by a biomimetic
      approach, namely, the biosilicification of silicic acids. The procedure consists
      of three simple steps: pattern generation of a polymerization initiator,
      (BrC(CH(3))(2)COO(CH(2))(11)S)(2), by microcontact printing; surface-initiated,
      atom-transfer radical polymerization of 2-(dimethylamino)ethyl methacrylate
      (DMAEMA) from the patterned area; and polycondensation of silicic acids. The
      tertiary amine-containing polymer, pDMAEMA, aided in the spatially controlled
      polycondensation of silicic acids on surfaces in the presence of phosphate ions,
      and micropatterns of silica on a gold substrate were successfully generated in
      combination with the technique of microcontact printing. The procedure could be
      extended to the controlled fabrication of silica patterns with any size, shape,
      or thickness.

PMID- 17193385
TI  - Fluorescent nanocrystals as colloidal probes in complex fluids measured by
      fluorescence correlation spectroscopy.
AB  - The diffusion properties of fluorescent colloidal CdSe and CdSe/ZnS nanocrystals
      (QDs) with different hydrophilic coatings were characterized in complex fluids
      such as actin solutions using fluorescence correlation spectroscopy (FCS). The
      hydrodynamic radii of the QDs were determined both in organic solvents and water.
      Attention was given to the potential artifacts arising from the fluorescence
      properties of the QDs. With increasing excitation intensities, the apparent
      particle concentration and diffusion times are overestimated if using a simple
      diffusion model. This can be explained by a numerical simulation. The diffusion
      behavior of QDs in actin networks of different concentrations was determined to
      demonstrate the potential use of nanocrystals as probes in soft biological
      matter. The decreasing diffusion coefficient of the nanocrystals with increasing
      actin concentration results in an intrinsic polymer viscosity of 0.12+/-0.02 ml
      mg(-1), in accordance with literature values.

PMID- 17193386
TI  - Synthesis of long indium nitride nanowires with uniform diameters in large
      quantities.
AB  - Large quantities of indium nitride (InN) nanowires are synthesized by the in situ
      nitriding of indium oxide (In(2)O(3)) powders in an ammonia (NH(3)) flux. Tens of
      milligrams of nanowires are obtained in one batch. Every 100 mg of In(2)O(3)
      starting powder can produce up to 65 mg of InN nanowires under the optimized
      conditions. The synthesized nanowires grow along the [001] direction with
      excellent crystallinity. They are of high purity and are 30-50 microm in length
      with an almost uniform diameter of about 100 nm. Photoluminescence measurements
      of the nanowires exhibit a strong peak at 707 nm. An optical bandgap of about 1.7
      eV is estimated based on the absorption spectrum. The experimental results also
      demonstrate that the approach of nitriding In(2)O(3) powders in situ is feasible
      for the synthesis of high-purity InN nanowires in large quantities, with good
      reproducibility and without catalyst materials. The synthesis of InN nanowires in
      large quantities would be of benefit to the further study and understanding of
      their intrinsic properties, as well as being advantageous for their potential
      application in nanodevices.

PMID- 17193389
TI  - Controlling nanotube chirality and crystallinity by doping.

PMID- 17193390
TI  - Nanomaterial-based amplified transduction of biomolecular interactions.
AB  - This article reviews progress in the development of nanomaterials for amplified
      biosensing and discusses different nanomaterial-based bioamplification
      strategies. Signal amplification has attracted considerable attention for
      ultrasensitive detection of disease markers and biothreat agents. The emergence
      of nanotechnology is opening new horizons for highly sensitive bioaffinity and
      biocatalytic assays and for novel biosensor protocols that employ electronic,
      optical, or microgravimetric signal transduction. Nucleic acids and antibodies
      functionalized with metal or semiconductor nanoparticles have been employed as
      amplifying tags for the detection of DNA and proteins. The coupling of different
      nanomaterial-based amplification platforms and amplification processes
      dramatically enhances the intensity of the analytical signal and leads to
      ultrasensitive bioassays. The successful realization of the new nanoparticle
      based signal amplification strategies requires proper attention to nonspecific
      adsorption issues. The implications of such nanoscale materials on amplified
      biodetection protocols and on the development of modern biosensors are discussed.

PMID- 17193391
TI  - Directed growth of well-aligned zinc silicate nanowires along the channels of
      surfactant-assembled mesoporous silica.

PMID- 17193392
TI  - Synthesis of gold nanoparticles using multifunctional peptides.

PMID- 17193393
TI  - Top-down fabrication of semiconductor nanowires with alternating structures along
      their longitudinal and transverse axes.

PMID- 17193394
TI  - Thermal stability and lasing of CdS nanowires coated by amorphous silica.

PMID- 17193395
TI  - Aligned single-crystalline Si nanowire arrays for photovoltaic applications.

PMID- 17193396
TI  - Electrical conductance of atomic contacts in liquid environments.

PMID- 17193397
TI  - Solid-state dye-sensitized solar cells combining a porous TiO2 film and a layer
      by-layer composite electrolyte.

PMID- 17193398
TI  - Manipulation of chemically synthesized FePt nanoparticles in water: core-shell
      silica/FePt nanocomposites.

PMID- 17193399
TI  - Synthesis and patterning of gold nanostructures on InP and GaAs via galvanic
      displacement.

PMID- 17193400
TI  - Metal (Mn, Co, and Cu) oxide nanocrystals from simple formate precursors.

PMID- 17193401
TI  - A liquid-Ga-filled carbon nanotube: a miniaturized temperature sensor and
      electrical switch.
AB  - Temperature control on the nanometer scale is a challenging task in many
      physical, chemical, and material science applications where small experimental
      volumes with high temperature gradients are used. The crucial difficulty is
      reducing the size of temperature sensors while keeping their sensitivity, working
      temperature range, and, most importantly, their simplicity and accuracy of
      temperature reading. In this work, we demonstrate the ultimate miniaturization of
      the classic thermometer using an expanding column of liquid gallium inside a
      multi-walled C nanotube for precise temperature measurements. We report that
      electrical conductivity through unfilled nanotube regions is diffusive with a
      resistance per unit length of approximately 10 kOmega microm(-1), whereas Ga
      filled segments of the nanotube show metallic behavior with a low resistance of
      approximately 100 Omega microm(-1). No noticeable Schottky barrier exists between
      the nanotube carbon shell and the inner Ga filling. Based on these findings, an
      individual carbon nanotube partially filled with liquid Ga is used as a
      temperature sensor and/or switch. The nanotube's electrical resistance decreases
      linearly with increasing temperature as the metallic Ga column expands inside the
      tube channel. In addition, the tube resistance drops sharply when two
      encapsulated Ga columns approaching each other meet inside the nanotube,
      producing a switching action that can occur at any predetermined temperature, as
      the Ga column position inside the nanotube can be effectively pre-adjusted by
      nanoindentation using an atomic force microscope.

PMID- 17193402
TI  - Growth of semiconducting GaN hollow spheres and nanotubes with very thin shells
      via a controllable liquid gallium-gas interface chemical reaction.
AB  - An in situ liquid gallium-gas interface chemical reaction route has been
      developed to synthesize semiconducting hollow GaN nanospheres with very small
      shell size by carefully controlling the synthesis temperature and the ammonia
      reaction gas partial pressure. In this process the gallium droplet does not act
      as a catalyst but rather as a reactant and a template for the formation of hollow
      GaN structures. The diameter of the synthesized hollow GaN spheres is typically
      20-25 nm and the shell thickness is 3.5-4.5 nm. The GaN nanotubes obtained at
      higher synthesis temperatures have a length of several hundreds of nanometers and
      a wall thickness of 3.5-5.0 nm. Both the hollow GaN spheres and nanotubes are
      polycrystalline and are composed of very fine GaN nanocrystalline particles with
      a diameter of 3.0-3.5 nm. The room-temperature photoluminescence (PL) spectra for
      the synthesized hollow GaN spheres and nanotubes, which have a narrow size
      distribution, display a sharp, blue-shifted band-edge emission peak at 3.52 eV
      (352 nm) due to quantum size effects.

PMID- 17193404
TI  - Guided growth of large-scale, horizontally aligned arrays of single-walled carbon
      nanotubes and their use in thin-film transistors.
AB  - A convenient process for generating large-scale, horizontally aligned arrays of
      pristine, single-walled carbon nanotubes (SWNTs) is described. The approach uses
      guided growth, by chemical vapor deposition (CVD), of SWNTs on miscut single
      crystal quartz substrates. Studies of the growth reveal important relationships
      between the density and alignment of the tubes, the CVD conditions, and the
      morphology of the quartz. Electrodes and dielectrics patterned on top of these
      arrays yield thin-film transistors that use the SWNTs as effective thin-film
      semiconductors. The ability to build high-performance devices of this type
      suggests significant promise for large-scale aligned arrays of SWNTs in
      electronics, sensors, and other applications.

PMID- 17193403
TI  - Synthesis of fullerene-like tantalum disulfide nanoparticles by a gas-phase
      reaction and laser ablation.
AB  - Motivated by the discovery of the C(60) molecule (buckminsterfullerene), the
      search for inorganic counterparts of this closed-cage nanostructure started in
      1992 with the discovery of nested fullerene-like nanoparticles of WS(2).
      Inorganic fullerene-like (IF) materials have since been found in numerous two
      dimensional compounds and are available in a variety of shapes that offer major
      applications such as in lubricants and nanocomposites. Various synthetic
      methodologies have been employed to achieve the right conditions for the
      constricted or templated growth needed for the occurrence of this new phase. In
      this study, IF-TaS(2) is produced from a volatile chloride precursor in the gas
      phase and in small yield by room temperature laser ablation both in argon and in
      liquid CS(2). For the gas-phase reaction, a high yield of IF nanoparticles was
      obtained between 400 and 600 degrees C with a low concentration of the precursor
      gas. The average size and the yield of the IF-TaS(2) nanoparticles decrease with
      temperature. Above 600 degrees C, IF nanoparticles were found in low yields and
      at sizes below 20 nm. The stability of the IF nanoparticles produced by the gas
      phase reaction is discussed in the light of two existing theoretical models.
      Laser ablation in argon leads to IF nanoparticles filled with clusters of TaS(2).
      Agglomeration of the nanoparticles can be avoided by laser ablation in liquid
      CS(2).

PMID- 17193405
TI  - Individualization of single-walled carbon nanotubes: is the solvent important?
AB  - The influence of different solvents on the individualization of single-walled
      carbon nanotubes (SWNTs) was investigated by several methods. A stable solution
      of individual SWNTs in o-dichlorobenzene was obtained by a combination of
      ultrasonication and ultracentrifugation. Atomic force microscopy height analysis
      confirmed that the final supernatant solution contained 85 % of individual tubes
      with a diameter equal to or less than 1.5 nm, which is consistent with the
      average diameter of arc-discharge tubes. Both the solvent and the
      ultracentrifugation speed are important parameters in determining the final
      degree of individualized SWNTs. Notably, the SWNTs were stable in o
      dichlorobenzene for more than eight months. This technique for obtaining highly
      individualized SWNTs in an organic solvent is expected to have great potential in
      many applications, such as functional materials and nanoelectronics.

PMID- 17193408
TI  - Asymmetric end-functionalization of carbon nanotubes.

PMID- 17193409
TI  - Physicochemical evaluation of the hot-injection method, a synthesis route for
      monodisperse nanocrystals.
AB  - The quintessence of the hot-injection method, a synthesis route for monodisperse,
      highly luminescent semiconductor nanocrystals, is reviewed. The separate stages
      of nucleation and growth of the nanocrystals are discussed in the framework of
      classical nucleation theory and an equilibrium model proposed by Debye. We also
      review the numerous adaptations of the original synthesis that currently provide
      colloidal nanocrystals with well-defined, size-dependent optical, electrical, and
      magnetic properties. The availability of these remarkable materials is one of the
      most promising developments in nanoscience and nanotechnology.

PMID- 17193410
TI  - A printable form of single-crystalline gallium nitride for flexible
      optoelectronic systems.

PMID- 17193411
TI  - Conformation and local environment dependent conductance of DNA molecules.

PMID- 17193412
TI  - Template-free hydrothermal synthesis of single-crystalline barium titanate and
      strontium titanate nanowires.

PMID- 17193413
TI  - Direct preparation and loading of lipid and polymer vesicles using inkjets.

PMID- 17193414
TI  - Atomic-resolution imaging of the nucleation points of single-walled carbon
      nanotubes.

PMID- 17193415
TI  - Nanocrystals as precursors for flexible functional films.

PMID- 17193416
TI  - Surface-acoustic-wave-enhanced alignment of thiolated carbon nanotubes on gold
      electrodes.

PMID- 17193417
TI  - Fabrication of thin, metallic films along the sidewalls of a topographically
      patterned stamp and their application in charge printing.

PMID- 17193418
TI  - Multigram-scale fabrication of monodisperse conducting polymer and magnetic
      carbon nanoparticles.

PMID- 17193419
TI  - Boron nitride nanocages synthesized by a moderate thermochemical approach.

PMID- 17193420
TI  - A magnetically separable, highly stable enzyme system based on nanocomposites of
      enzymes and magnetic nanoparticles shipped in hierarchically ordered,
      mesocellular, mesoporous silica.

PMID- 17193421
TI  - Cell distribution profiles in three-dimensional scaffolds with inverted-colloidal
      crystal geometry: modeling and experimental investigations.
AB  - Limited ingrowth of stromal cells is observed when a three-dimensionally ordered
      scaffold possessing inverted-colloidal-crystal geometry is used to culture
      adherent cells. In this work, a computational model explaining, as well as
      predicting, experimental cell distributions is developed. It incorporates a
      modified Contois cell-growth model that includes the effects of nutrient
      saturation, competitive product inhibition, and cell-contact inhibition to
      describe the scaffold-cell system. Our results agree with the hypothesis that the
      rapid growth of cells on the surface of the scaffold depletes the nutrient supply
      to the core, resulting in the preferential growth on the exterior of the
      scaffold. When the cells are cultured in a scaffold subjected to a uniform
      velocity field, they penetrate to a greater extent into the scaffold core.
      Alternative seeding and culture strategies are suggested and evaluated.

PMID- 17193422
TI  - Type-II CdSe/CdTe/ZnTe (core-shell-shell) quantum dots with cascade band edges:
      the separation of electron (at CdSe) and hole (at ZnTe) by the CdTe layer.
AB  - The rational design and synthesis of CdSe/CdTe/ZnTe (core-shell-shell) type-II
      quantum dots are reported. Their photophysical properties are investigated via
      the interband CdSe-->ZnTe emission and its associated relaxation dynamics. In
      comparison to the strong CdSe (core only) emission (lambda(max) approximately 550
      nm, Phi(f) approximately 0.28), a moderate CdSe-->CdTe emission (lambda(max)
      approximately 1026 nm, Phi(f) approximately 1.2 x 10(-3)) and rather weak CdSe-
      >ZnTe interband emission (lambda(max) approximately 1415 nm, Phi(f) approximately
      1.1 x 10(-5)) are resolved for the CdSe/CdTe/ZnTe structure (3.4/1.8/1.3 nm).
      Capping CdSe/CdTe with ZnTe results in a distant electron-hole separation between
      CdSe (electron) and ZnTe (hole) via an intermediate CdTe layer. In the case of
      the CdSe/CdTe/ZnTe structure, a lifetime as long as 150 ns is observed for the
      CdSe-->ZnTe (1415 nm) emission. This result further indicates an enormously long
      radiative lifetime of approximately 10 ms. Upon excitation of the CdSe/CdTe/ZnTe
      structure, the long-lived charge separation may further serve as an excellent
      hole carrier for catalyzing the redox oxidation reaction.

PMID- 17193423
TI  - Nanometer-scale modification and welding of silicon and metallic nanowires with a
      high-intensity electron beam.
AB  - We demonstrate that a high-intensity electron beam can be applied to create
      holes, gaps, and other patterns of atomic and nanometer dimensions on a single
      nanowire, to weld individual nanowires to form metal-metal or metal-semiconductor
      junctions, and to remove the oxide shell from a crystalline nanowire. In single
      crystalline Si nanowires, the beam induces instant local vaporization and local
      amorphization. In metallic Au, Ag, Cu, and Sn nanowires, the beam induces rapid
      local surface melting and enhanced surface diffusion, in addition to local
      vaporization. These studies open up a novel approach for patterning and
      connecting nanomaterials in devices and circuits at the nanometer scale.

PMID- 17193426
TI  - Formation of hexagonal mesoporous silica in submicrometer channels.

PMID- 17193427
TI  - Nanoscience, nanotechnology, and chemistry.

PMID- 17193428
TI  - Chemically functionalized carbon nanotubes.
AB  - Since their discovery, carbon nanotubes have attracted the attention of many a
      scientist around the world. This extraordinary interest stems from their
      outstanding structural, mechanical, and electronic properties. In fact, apart
      from being the best and most easily available one-dimensional (1D) model system,
      carbon nanotubes show strong application potential in electronics, scanning probe
      microscopy, chemical and biological sensing, reinforced composite materials, and
      in many more areas. While some of the proposed applications remain still a far
      off dream, others are close to technical realization. Recent advances in the
      development of reliable methods for the chemical functionalization of the
      nanotubes provide an additional impetus towards extending the scope of their
      application spectrum. In particular, covalent modification schemes allow
      persistent alteration of the electronic properties of the tubes, as well as to
      chemically tailor their surface properties, whereby new functions can be
      implemented that cannot otherwise be acquired by pristine nanotubes.

PMID- 17193429
TI  - Nanoengineered polymer capsules: tools for detection, controlled delivery, and
      site-specific manipulation.
AB  - We present the concept of multifunctional nanoengineered polymer capsules and
      outline their applications as new drug delivery systems or supramolecular
      toolboxes containing, for example, enzymes capable of converting nontoxic
      prodrugs into toxic drugs at a designated location. Such functionalized
      nanocontainers offer a wide range of applications including enzymatic catalysis,
      controlled release, and directed drug delivery in medicine due to their
      multifunctionality. The unique advantage of capsules in comparison to other
      systems is that they can be functionalized or loaded simultaneously with the
      above-mentioned components, thus permitting multifunctional processes in single
      cells.

PMID- 17193430
TI  - Directed rotational motion of microscale objects using interfacial tension
      gradients continually generated via catalytic reactions.

PMID- 17193431
TI  - Signal transmission from individual mammalian nerve cell to field-effect
      transistor.

PMID- 17193432
TI  - Solid-state synthesis of "bamboo-like" and straight carbon nanotubes by
      thermolysis of hexa-peri-hexabenzocoronene-cobalt complexes.

PMID- 17193433
TI  - Optical and electrochemical detection of NADH and of NAD+-dependent biocatalyzed
      processes by the catalytic deposition of copper on gold nanoparticles.

PMID- 17193434
TI  - A general chemical conversion method to various semiconductor hollow structures.

PMID- 17193435
TI  - Spontaneous formation of ordered 2D and 3D superlattices of ZnO nanocrystals.

PMID- 17193436
TI  - Evolution of nanocrystallinity in periodic mesoporous anatase thin films.
AB  - Herein we report the first kinetic study of the intrachannel wall phase
      transition of amorphous titania to nanocrystalline anatase for periodic
      mesoporous titania thin films, monitored by time-resolved in situ high
      temperature X-ray diffraction. Structural transformations associated with the
      phase transition are further probed by high-resolution scanning electron
      microscopy and transmission electron microscopy. The model found to be most
      consistent with the kinetic data involves 1D diffusion-controlled growth of
      nanocrystalline anatase within the spatial confines of the channel walls of the
      mesostructure. The observation of anisotropic, rod-shaped anatase nanocrystals
      preferentially aligned along the channel axis implies that the framework of the
      liquid-crystal-templated mesostructure guides the crystal growth.

PMID- 17193437
TI  - Characterization of chiral mesoporous materials by transmission electron
      microscopy.
AB  - By using transmission electron microscopy (TEM), the chirality of novel
      mesoporous materials has been studied. In addition, a computer simulation that
      uses a simple structural model was employed. The existence of chiral channels
      inside a tubelike material was confirmed by the observation of fringes along the
      length of the tubes. The chiral pitch of the channels was measured from the
      intermittent period, the chirality (right- or left-handed) was determined from
      the tilt direction of a tube compared with the direction of incident electrons
      and the curvature direction of the curved intermitted fringes as viewed in the
      TEM images.

PMID- 17193438
TI  - Tunable whispering gallery mode emission from quantum-dot-doped microspheres.
AB  - We describe the synthesis of quantum-dot (QD) doped silica microspheres and a
      method by which it is possible to fine-tune the position of the whispering
      gallery modes (WGMs) produced by the fluorescence emission of CdSe@ZnS doped
      silica microspheres (5.06 mum in diameter). The method is based on small
      perturbations to the sphere's refractive index caused by adsorption of thin
      layers of polyelectrolytes and modification of the radial position of the
      nanocrystals within the microsphere by means of deposited silica shells.

PMID- 17193439
TI  - Molecular printboards on silicon oxide: lithographic patterning of cyclodextrin
      monolayers with multivalent, fluorescent guest molecules.
AB  - Three compounds bearing multiple adamantyl guest moieties and a fluorescent dye
      have been synthesized for the supramolecular patterning of beta-cyclodextrin (CD)
      host monolayers on silicon oxide using microcontact printing and dip-pen
      nanolithography. Patterns created on monolayers on glass were viewed by laser
      scanning confocal microscopy. Semi-quantitative analysis of the patterns showed
      that with microcontact printing approximately a single monolayer of guest
      molecules is transferred. Exposure to different rinsing procedures showed the
      stability of the patterns to be governed by specific supramolecular multivalent
      interactions. Patterns of the guest molecules created at CD monolayers were
      stable towards thorough rinsing with water, whereas similar patterns created on
      poly(ethylene glycol) (PEG) reference monolayers were instantly removed. The
      patterns on CD monolayers displayed long-term stability when stored under N(2),
      whereas patterns at PEG monolayers faded within a few weeks due to the diffusion
      of fluorescent molecules across the surface. Assemblies at CD monolayers could be
      mostly removed by rinsing with a concentrated CD solution, demonstrating the
      reversibility of the methodology. Patterns consisting of different guest
      molecules were produced by microcontact printing of one guest molecule and
      specific adsorption of a second guest molecule from solution to non-contacted
      areas, giving well-defined alternating assemblies. Fluorescent features of sub
      micrometer dimensions were written using supramolecular dip-pen nanolithography.

PMID- 17193444
TI  - Nanoscience and nanotechnology: a personal view of a chemist.

PMID- 17193443
TI  - Low-temperature, controlled synthesis of carbon nanotubes.

PMID- 17193445
TI  - DNA nanodevices.
AB  - The molecular recognition properties of DNA molecules combined with the distinct
      mechanical properties of single and double strands of DNA can be utilized for the
      construction of nanodevices, which can perform ever more tasks with possible
      applications ranging from nanoconstruction to intelligent drug delivery. With the
      help of DNA it is possible to construct machinelike devices that are capable of
      rotational motion, pulling and stretching, or even unidirectional motion. It is
      possible to devise autonomous nanodevices, to grab and release molecules, and
      also to perform simple information-processing tasks.

PMID- 17193446
TI  - Molding and replication of ceramic surfaces with nanoscale resolution.
AB  - The design of reproducible and more efficient nanofabrication routes has become a
      very active research field in recent years. In particular, the development of new
      methods for micro- and nanopatterning materials surfaces has attracted the
      attention of many researchers in industry and academia as a consequence of the
      growing relevance of patterned surfaces in many technological fields, ranging
      from optoelectronics to biotechnology. In this work we explore, discuss, and
      demonstrate the possibility of extending the well-known molding and replication
      strategy for patterning ceramic materials with nanoscale resolution. To achieve
      this goal we have combined physical deposition methods, molecule-thick anti
      sticking coatings, and nanostructured substrates as master surfaces. This new
      perspective on an "old technology", as molding is, provides an interesting
      alternative for high-resolution, direct surface-relief patterning of materials
      that currently requires expensive and time-consuming lithographic approaches.

PMID- 17193447
TI  - Tuning the field-emission properties of tungsten oxide nanorods.

PMID- 17193448
TI  - Controlled assembly of preformed ceria nanocrystals into highly ordered 3D
      nanostructures.

PMID- 17193449
TI  - Embedded carbon-nanotube-stiffened polymer surfaces.

PMID- 17193450
TI  - Flexible wurtzite-type ZnS nanobelts with quantum-size effects: a
      diethylenetriamine-assisted solvothermal approach.

PMID- 17193451
TI  - Gold nanoparticles are taken up by human cells but do not cause acute
      cytotoxicity.

PMID- 17193452
TI  - Modular self-assembly of DNA lattices with tunable periodicity.

PMID- 17193453
TI  - Sequential synthesis of type II colloidal CdTe/CdSe core-shell nanocrystals.
AB  - Colloidal type II CdTe/CdSe nanocrystals were synthesized by sequential addition
      of a tri-n-octylphosphine telluride (TOPTe)/TOP solution and several shell
      precursor solutions to a CdO/TOP solution; the shell-precursor solutions
      consisted of CdO and TOPSe in TOP. For the growth of the CdTe core, the TOPTe/TOP
      solution was swiftly added to the CdO/TOP solution at a higher temperature (300
      degrees C) than the growth temperature (250 degrees C). For the growth of the
      CdSe shell, in contrast, the CdO/TOPSe/TOP solution was slowly added to the
      CdTe/TOP solution at a lower temperature than the growth temperature (200-240
      degrees C). The temporal evolution of the optical properties of the growing core
      shell nanocrystals was monitored in detail. During the growth of the CdSe shell,
      the core-shell nanocrystals exhibited interesting changes in photoluminescence
      (PL) properties. The highest PL efficiency (approximately 38 %) was detected from
      core-shell nanocrystals with a CdSe shell thickness of 0.4-0.5 nm (indicated by
      TEM); the formation of the first monolayer is proposed. Our synthetic approach is
      well suited to a practical realization of engineering materials with bandgaps in
      the near-IR and IR spectral ranges.

PMID- 17193454
TI  - Recrystallization of bacterial S-layers on flat polyelectrolyte surfaces and
      hollow polyelectrolyte capsules.
AB  - Polyelectrolyte multilayer (PE) deposition and S-layer technology have been
      combined to make novel robust biomimetic surfaces and membranes. Isolated
      subunits of the bacterial cell surface layer from Bacillus sphaericus CCM2177
      SbpA was self-assembled on PE multilayer supports, with the composition of the
      multilayer playing a crucial role in determining the structure of the resulting
      supported protein layers. Flat substrates were studied using atomic force
      microscopy and neutron reflectometry; protein on suitable PE combinations showed
      a crystalline structure with lattice constants equal to those found in vivo on
      bacterial surfaces. The mechanical stability of the S-layer is higher when
      recrystallized on PEs than directly on silicon supports. The recrystallization
      process was subsequently used to coat colloidal particles, permitting the
      determination of zeta potentials before and after coating. Hollow capsules could
      also be coated in the same way, as proven by various techniques. Our results
      suggest that electrostatic interactions via divalent cations are important for
      the assembly process. The results also demonstrate that the versatility of the PE
      multilayer membranes can be successfully combined with the well-defined surface
      chemistry and structure of 2D protein crystals.

PMID- 17193455
TI  - A general in situ hydrothermal rolling-up formation of one-dimensional, single
      crystalline lead telluride nanostructures.
AB  - In this study we demonstrate that one-dimensional (1D) nanostructured lead
      telluride (PbTe) can be synthesized in a hydrothermal reaction between lead foil
      and tellurium powder. The resulting materials were characterized by X-ray
      diffraction, scanning electron microscopy, and transmission electron microscopy.
      The formation of the 1D structure can be explained by an in situ hydrothermal
      rolling-up mechanism whereby PbTe is formed hydrothermally and deposited on the
      lead substrate. The lead underneath the PbTe layer is then selectively etched by
      a cetyltrimethylammonium bromide solution, thus allowing the PbTe to roll up into
      1D structures. This method can be extended to prepare other 1D tellurides,
      including CdTe, Cu(2)Te, and Ag(2)Te.

PMID- 17193458
TI  - Small colorful ribbons for nanoscience.

PMID- 17193460
TI  - High-rate unidirectional energy transfer in directly assembled CdTe nanocrystal
      bilayers.

PMID- 17193459
TI  - Carbon nanotubes for microelectronics?
AB  - Despite all prophecies of its end, silicon-based microelectronics still follows
      Moore's Law and continues to develop rapidly. However, the inherent physical
      limits will eventually be reached. Carbon nanotubes offer the potential for
      further miniaturization as long as it is possible to selectively deposit them
      with defined properties.

PMID- 17193461
TI  - Noble metal nanoparticles deposited on self-assembled monolayers by pulsed laser
      deposition show coulomb blockade at room temperature.
AB  - Nanometer-sized noble-metal clusters are fabricated on top of alkylthiolate self
      assembled monolayers (SAMs) on annealed gold by pulsed laser deposition at
      elevated pressures. The size distribution of the clusters depends on the metal
      and on the pressure during the deposition. Scanning tunneling microscopy (STM)
      and conductive probe atomic force microscopy (CP-AFM) showed that the metal
      clusters are insulated from the substrate on top of the SAM. Coulomb blockades
      could be measured at room temperature by STM for palladium clusters on
      decanethiol SAMs.

PMID- 17193462
TI  - Molecular dynamics study of the mechanical and electronic properties of carbon
      nanotubes.

PMID- 17193463
TI  - Direct synthesis of a bimodal nanosponge based on FePt and ZnS.

PMID- 17193464
TI  - Application of carbon nanotube AFM probes to the characterization of mesoporous
      materials.

PMID- 17193465
TI  - Highly efficient guiding of microtubule transport with imprinted CYTOP
      nanotracks.

PMID- 17193466
TI  - Hollow thermoresponsive microgels.
AB  - Thermoresponsive poly(N-isopropyl acrylamide) (pNIPAm) microgels possessing a
      hollow structure have been synthesized from core-shell nanoparticles upon
      oxidation of the particle core, followed by removal of the produced polymer
      segments by centrifugation. N,N'-(1,2-dihydroxyethylene)bisacrylamide (DHEA) is
      used as a cross-linker for preparing the degradable core, whereas N,N'
      methylenebis(acrylamide) (BIS) is used as a cross-linker to add a nondegradable
      pNIPAm shell. Addition of NaIO(4) to a suspension of these particles in water
      leads to controlled degradation of the particle core by cleavage of the 1,2
      glycol bond in DHEA. Fluorescence spectroscopy, UV/Vis spectroscopy, and photon
      correlation spectroscopy are used to characterize the hollow particles produced.

PMID- 17193467
TI  - Direct observation of the growth process of MgO nanoflowers by a simple chemical
      route.
AB  - Novel flowerlike nanostructures consisting of MgO nanofibers were successfully
      synthesized by a simple chemical route with H(2)O at 950 degrees C in an Ar
      atmosphere. Various durations of heating gave different growth stages that led to
      varied product morphologies. The synthesized products were systematically studied
      by X-ray powder diffraction, scanning electron microscopy, high-resolution
      transmission electron microscopy, and energy-dispersive X-ray analysis. The
      results show that the nucleation and growth process of the nanoflowers seems to
      be a vapor-solid mechanism, and that the total heating time during the reaction
      process is a critical factor for the development of MgO nanoflowers. Initially,
      Mg particles formed on the Si substrate, followed by the formation of MgO
      clusters as nucleation centers on the magnesium melt surface and the nucleation
      of short MgO nanofibers, then growth of the MgO nanofibers occurred, and finally
      MgO nanoflowers were formed. Besides nanoflowers, novel hierarchical MgO
      nanostructures were also observed. These nanostructures may be used as three
      dimensional composite materials and as supports for other materials.

PMID- 17193468
TI  - Temperature-dependent growth of germanium oxide and silicon oxide based
      nanostructures, aligned silicon oxide nanowire assemblies, and silicon oxide
      microtubes.
AB  - We demonstrate the temperature-dependent growth of germanium oxide and silicon
      oxide based composite nanostructures (multiple nanojunctions of Ge nanowires and
      SiO(x) nanowires, Ge-filled SiO(2) nanotubes, Ge/SiO(2) coaxial nanocables, and a
      variety of interesting micrometer-sized structures), aligned SiO(x) nanowire
      assemblies, and SiO(x) microtubes. The structures were characterized by SEM, TEM,
      energy-dispersive X-ray spectroscopy, and electron diffraction. The combination
      of laser ablation of a germanium target and thermal evaoporation of silicon
      monoxide powders resulted in the formation of Ge and SiO(x) species in a carrier
      gas; the nano/micro-sized structures grow by either a Ge-catalyzed vapor-liquid
      solid or a Ge-nanowire-templated vapor-solid process.

PMID- 17193469
TI  - Fabrication of nanoscale rings, dots, and rods by combining shadow nanosphere
      lithography and annealed polystyrene nanosphere masks.
AB  - The application of shadow nanosphere lithography for the preparation of large
      area, two-dimensional, metallic nanostructures of different shape is described.
      Through changing the mask morphology by temperature processing and varying the
      evaporation conditions, particles with morphologies such as rings, rods, and dots
      have been produced. This process allows outstanding control of the size and
      morphology of the particles. The efficient technique is shown to scale down the
      size of metallic nanoparticles from 200 to 30 nm, while preserving the original
      nanosphere spacing and order. The 150-nm-diameter Fe rings produced by this
      method show ferromagnetic behavior, which was predicted by theoretical
      simulation. All the experimental results were confirmed by computer simulations,
      which also showed the possibility of creating periodic arrays of any other
      geometrical shape.

PMID- 17193470
TI  - Methods for fabricating microarrays of motile bacteria.
AB  - Motile bacterial cell microarrays were fabricated by attaching Escherichia coli K
      12 cells onto predesigned 16-mercaptohexadecanoic acid patterned microarrays,
      which were covalently functionalized with E. coli antibodies or poly-L-lysine. By
      utilizing 11-mercaptoundecyl-penta(ethylene glycol) or 11-mercapto-1-undecanol as
      passivating molecules, nonspecific binding of E. coli was significantly reduced.
      Microcontact printing and dip-pen nanolithography were used to prepare
      microarrays for bacterial adhesion, which was studied by optical fluorescence and
      atomic force microscopy. These data indicate that single motile E. coli can be
      attached to predesigned line or dot features and binding can occur via the cell
      body or the flagella of bacteria. Adherent bacteria are viable (remain alive and
      motile after adhesion to patterned surface features) for more than four hours.
      Individual motile bacterial cells can be placed onto predesigned surface features
      that are at least 1.3 microm in diameter or larger. The importance of controlling
      the adhesion of single bacterial cell to a surface is discussed with regard to
      biomotor design.

PMID- 17193471
TI  - Single-walled carbon nanotubes under the influence of dynamic coordination and
      supramolecular chemistry.
AB  - A dynamic coordinative-directed solubilization of single-walled carbon nanotubes
      (SWNTs) in aqueous solutions has been achieved through a combination of a Zn(II)
      metalloporphyrin complex and a cis-protected Pd(II) complex, which are believed
      to form charged acyclic and/or cyclic adducts on or around the side walls of
      SWNTs. The solubilization of SWNTs in aqueous solution only occurs when these
      acyclic and/or cyclic complexes are allowed to enter simultaneously into a self
      assembly process with SWNTs under mild conditions. The aqueous solubility
      properties that these dynamic complexes confer upon SWNTs are believed to involve
      noncovalent bonding interactions between the two entities. They have been probed
      in solution using ultraviolet and visible absorption spectroscopy and in thin
      films using high-resolution transmission electron microscopy. The supramolecular
      electronic effects that the individual components of their acyclic and/or cyclic
      complexes impart upon a single semiconducting SWNT have been probed within a
      nanotube field-effect transistor device.

PMID- 17193474
TI  - Synthesis, properties, and applications of iron nanoparticles.
AB  - Iron, the most ubiquitous of the transition metals and the fourth most plentiful
      element in the Earth's crust, is the structural backbone of our modern
      infrastructure. It is therefore ironic that as a nanoparticle, iron has been
      somewhat neglected in favor of its own oxides, as well as other metals such as
      cobalt, nickel, gold, and platinum. This is unfortunate, but understandable.
      Iron's reactivity is important in macroscopic applications (particularly
      rusting), but is a dominant concern at the nanoscale. Finely divided iron has
      long been known to be pyrophoric, which is a major reason that iron nanoparticles
      have not been more fully studied to date. This extreme reactivity has
      traditionally made iron nanoparticles difficult to study and inconvenient for
      practical applications. Iron however has a great deal to offer at the nanoscale,
      including very potent magnetic and catalytic properties. Recent work has begun to
      take advantage of iron's potential, and work in this field appears to be
      blossoming.

PMID- 17193475
TI  - Reaction kinetics in a tight spot.
AB  - The standard analysis of reaction networks based on deterministic rate equations
      fails in confined geometries, commonly encountered in fields such as
      astrochemistry, thin-film growth and cell biology. In these systems the small
      reactant population implies anomalous behavior of reaction rates, which can be
      accounted for only by following the full distribution of reactant numbers.

PMID- 17193476
TI  - Cell-targeting multifunctional nanospheres with both fluorescence and magnetism.

PMID- 17193477
TI  - Halloysite nanotubes as biomimetic nanoreactors.

PMID- 17193478
TI  - Large-scale assembly of single-crystal silver nanoprism monolayers.

PMID- 17193479
TI  - Extracellular biosynthesis of bimetallic Au-Ag alloy nanoparticles.

PMID- 17193480
TI  - Fabrication of polypyrrole wires between microelectrodes.

PMID- 17193481
TI  - Branched wires of CdTe nanocrystals using amphiphilic molecules as templates.

PMID- 17193482
TI  - Dispersable carbon nanotube/gold nanohybrids: evidence for strong electronic
      interactions.

PMID- 17193483
TI  - Dynamics of grain boundaries in two-dimensional hydrogen-bonded molecular
      networks.
AB  - The temporal evolution of domain boundaries of hydrogen-bonded molecular
      monolayers at the liquid-solid interface is evaluated by recording series of
      subsequent scanning tunneling microscopy (STM) images. Comparison of dissimilar
      benzene carboxylic acids reveals a clear distinction between one- and two
      dimensional H-bonded network structures. Trimesic acid forms a two-dimensionally
      H-bonded networked structure, whereas terephthalic acid organizes in a dense
      packing of H-bonded linear chains on a graphite surface. In addition, TMA forms a
      sixfold lattice on a threefold graphite substrate, whereas TPA exhibits only a
      twofold lattice, causing a high grain-boundary line energy for the latter. In the
      case of TMA the nanostructure was mostly stable during the observation time. For
      TPA, Ostwald ripening-that is, the growth of larger islands at the expense of
      smaller islands-was observed. To explain the various experimentally observed
      timescales of the dynamics occurring at grain boundaries, molecular mechanics
      simulations were applied to calculate the binding energy of edge molecules, that
      is, the line energy, of finite islands of both trimesic and terephthalic acid on
      a graphite substrate.

PMID- 17193484
TI  - Chemical vapor synthesis of size-selected zinc oxide nanoparticles.
AB  - ZnO can be regarded as one of the most important metal oxide semiconductors for
      future applications. Similar to silicon in microelectronics, it is not only
      important to obtain nanoscale building blocks of ZnO, but also extraordinary
      purity has to be ensured. A new gas-phase approach to obtain size-selected,
      nanocrystalline ZnO particles is presented. The tetrameric alkyl-alkoxy zinc
      compound [CH(3)ZnOCH(CH(3))(2)](4) is chemically transformed into ZnO, and the
      mechanism of gas-phase transformation is studied in detail. Furthermore, the
      morphological genesis of particles via gas-phase sintering is investigated, and
      for the first time a detailed model of the gas-phase sintering processes of ZnO
      is presented. Various analytical techniques (powder XRD, TEM/energy-dispersive X
      ray spectroscopy, magic-angle spinning NMR spectroscopy, FTIR spectroscopy, etc.)
      are used to investigate the structure and purity of the samples. In particular,
      the defect structure of the ZnO was studied by photoluminescence spectroscopy.

PMID- 17193486
TI  - Preparation and characterization of aligned carbon nanotube-ruthenium oxide
      nanocomposites for supercapacitors.
AB  - A novel type of ruthenium oxide (RuO(2))-modified multi-walled carbon nanotube
      (MWNT) nanocomposite electrode (RuO(2)/MWNT) for supercapacitors has been
      prepared. The nanocomposites were formed by depositing Ru by magnetic-sputtering
      in an Ar/O(2) atmosphere onto MWNTs, which were synthesized on Ta plates by
      chemical vapor deposition. Cyclic voltammetry, chronopotentiometry, and
      electrochemical impedance measurements were applied to investigate the
      performance of the RuO(2)/MWNT nanocomposite electrodes. The capacitance of the
      MWNT electrodes in 1.0 M H(2)SO(4) is significantly increased from 0.35 to 16.94
      mF cm(-2) by modification with RuO(2). The RuO(2) film on the surface of the
      nanotubes is composed of small crystal grains with tilted bundle-like
      microstructures, as observed by transmission electron microscopy (TEM) and
      scanning electron microscopy (SEM). The results demonstrate a promising route to
      prepare RuO(2)/MWNT-based double-layer supercapacitors.

PMID- 17193485
TI  - Vertically aligned carbon-nanotube arrays showing Schottky behavior at room
      temperature.
AB  - Vertically aligned carbon-nanotube (CNT) arrays were fabricated in the thin-film
      anodic aluminum oxide (AAO) templates on silicon wafers utilizing a niobium (Nb)
      thin film as the source electrode. The average diameter of the CNTs was 25 nm,
      and the number density was 3 x 10(10) cm(-2). The CNT arrays synthesized at 700
      degrees C and above exhibited Schottky behavior even at 300 K, with energy gaps
      between 0.2 eV and 0.3 eV. However, individual CNTs obtained by removal of the
      template behaved as resistors at 300 K. The CNT/Nb oxide/Nb junction is thought
      to be responsible for the Schottky behavior. This structure can be a useful
      cornerstone in the fabrication of nanotransistors operating at room temperature.

PMID- 17193487
TI  - Symmetric and asymmetric Ostwald ripening in the fabrication of homogeneous core
      shell semiconductors.
AB  - Two methodic concepts, symmetric and asymmetric Ostwald ripening, are elucidated
      by solution-route syntheses of oxide and sulfide semiconductors. While the
      original shape of a crystallite aggregate forms the exterior appearance, the
      preorganization of the crystallites determines the ultimate interior space
      structure of the aggregate upon Ostwald ripening. Further investigations on the
      design of crystallite preorganization and control of the solution process will
      allow the construction of complex architectures, including nonspherical
      configurations.

PMID- 17193491
TI  - The tube or the helix? This is the question: towards the fully controlled DNA
      directed assembly of carbon nanotubes.

PMID- 17193492
TI  - Recent developments in nanofabrication using ion projection lithography.
AB  - Ion projection lithography (IPL) is an emerging technology and a major candidate
      for the next-generation lithography (NGL) designed to complement and supplement
      current optical lithographic techniques for future chip manufacturing. In this
      Review, the recent developments of IPL technology are examined with an emphasis
      on its ability to fabricate a wide variety of nanostructures for the
      semiconductor industry. Following an introduction of the uniqueness and strength
      of the technology, the basics of ion-source development and ion-target
      interactions with and without chemical enhancement are presented. The
      developments in equipment systems, masks, and resists are subsequently studied.
      The resolution of printed nanostructures and the corresponding throughput of the
      current system are assessed for NGL. Finally, concluding remarks are presented to
      summarize the strengths and weaknesses of the current technology and to suggest
      the scope for future improvement.

PMID- 17193493
TI  - Tone reversal of an AFM lateral force image due to hybridization of
      oligonucleotides immobilized on polymers.

PMID- 17193494
TI  - Manipulating the charging energy of nanocrystal arrays.

PMID- 17193495
TI  - Parallel fabrication of DNA-aligned metal nanostructures in microelectrode gaps
      by a self-organization process.

PMID- 17193496
TI  - Polyaniline nanofiber composites with metal salts: chemical sensors for hydrogen
      sulfide.

PMID- 17193497
TI  - Fabrication via electrochemical oxidation of self-assembled monolayers and site
      selective derivatization of surface templates.

PMID- 17193498
TI  - A nanofountain probe with Sub-100 nm molecular writing resolution.

PMID- 17193499
TI  - A selective chemical sensor based on the plasmonic response of phosphinine
      stabilized gold nanoparticles hosted on periodically organized mesoporous silica
      thin layers.

PMID- 17193500
TI  - A method to evaluate the tensile strength and stress-strain relationship of
      carbon nanofibers, carbon nanotubes, and C-chains.
AB  - A method is introduced to assess the tensile strength of carbon nanofibers,
      carbon nanotubes (CNTs), and linear chains of carbon atoms (C-chains) obtained
      from thin amorphous carbon films by electron irradiation. Transmission electron
      microscopy images show that the nanofibers undergo a radiation-induced necking
      process, characterized by CNT formation and often followed by the formation of a
      C-chain. Simulations of the necking process are carried out to determine the
      tensile stress supported by the nanofiber and CNT neck.

PMID- 17193501
TI  - Phase separation micromolding: a new generic approach for microstructuring
      various materials.
AB  - Phase separation micromolding (PSmicroM) is a versatile microfabrication
      technique that can be used to structure a very broad range of polymers, including
      block copolymers and biodegradable and conductive polymers without the need for
      clean-room facilities. By incorporating a subsequent process step, carbon,
      ceramic, and metallic microstructures can also be fabricated from a polymeric or
      hybrid precursor. The replication process is straightforward and cost-effective.
      It relies on phase separation of a polymer solution while in contact with a
      structured mold. Intrinsic shrinkage during the phase separation facilitates the
      release of the replica from the mold, which increases the reliability of the
      process even at small feature sizes, thin polymer films, or high aspect ratios.
      Under suitable circumstances perforation of the polymer film can be obtained,
      resulting in completely open "through" microstructures. Furthermore, porosity can
      be introduced in a microstructure, which may result in unknown functionalities.

PMID- 17193502
TI  - Control of the molecular alignment inside liquid-crystal droplets by use of laser
      tweezers.
AB  - Here, we demonstrate how the light-induced birefringence due to the dipole
      molecular realignment and anisotropic polarizability of a nematic liquid crystal
      inside a droplet changes the droplet's radial (and thus optically isotropic)
      structure into a birefringent one. This intensity-dependent change of
      birefringence can be understood in terms of the anisotropic polarizability and
      orientational optical nonlinear effect. Birefringence induced by laser tweezers
      changes the momentum of the passing light. In turn, for the circularly polarized
      tweezers, this change generates an angular momentum change large enough to spin
      micrometer-sized droplets. For the linearly polarized tweezers, the molecular
      ordering generates momentum, which laterally displaces the droplet. It is shown
      that the optical nonlinearity can be "large" enough to have mechanical
      (ponderomotive) implications, that is, it allows control of the movement and
      position of micro-objects with submicrometer resolution. The optically induced
      molecular alignment controlled by the polarization and power of the laser
      tweezers allows one to actuate, rotate, and translate objects which are up to
      10(3)-10(4) times larger than the constituent molecules themselves.

PMID- 17193506
TI  - Flow Focusing: a versatile technology to produce size-controlled and specific
      morphology microparticles.
AB  - The Flow Focusing platform is especially advantageous for micro- and nanoparticle
      production. This versatile technique is amenable to designing the size, surface
      treatment and internal topology of the particles; mechanical stresses are minimal
      an optimal feature for the manipulation of delicate substances. Multiplexing and
      high-rate production are readily implemented. Adaptive operational design can
      lead, in one single step, to finely tuned microcapsules encasing different
      products within a targeted morphology. This achievement is of great significance
      for most microcapsule applications in the biosciences (for example, drug
      delivery, cell encapsulation, and the production of bead arrays).

PMID- 17193505
TI  - The organometallic synthesis of bifunctional core/shell nanoparticles.

PMID- 17193507
TI  - Supramolecular templating of single and double nanohelices of cadmium sulfide.

PMID- 17193508
TI  - Assembly of gold nanoparticles using genetically engineered polypeptides.

PMID- 17193509
TI  - An engineered virus as a scaffold for three-dimensional self-assembly on the
      nanoscale.

PMID- 17193510
TI  - On the generation of free radical species from quantum dots.

PMID- 17193511
TI  - Using gene regulation to program DNA-based molecular devices.

PMID- 17193512
TI  - Size-dependent photoconductance in SnO2 nanowires.

PMID- 17193514
TI  - Self-organized high-aspect-ratio nanoporous zirconium oxides prepared by
      electrochemical anodization.

PMID- 17193513
TI  - Crystallography and surface faceting of germanium nanowires.

PMID- 17193515
TI  - A tunnel current in self-assembled monolayers of 3
      mercaptopropyltrimethoxysilane.

PMID- 17193516
TI  - Water-soluble sacrificial layers for surface micromachining.
AB  - This manuscript describes the use of water-soluble polymers for use as
      sacrificial layers in surface micromachining. Water-soluble polymers have two
      attractive characteristics for this application: 1) They can be deposited
      conveniently by spin-coating, and the solvent removed at a low temperature (95
      150 degrees C), and 2) the resulting layer can be dissolved in water; no
      corrosive reagents or organic solvents are required. This technique is therefore
      compatible with a number of fragile materials, such as organic polymers, metal
      oxides and metals-materials that might be damaged during typical surface
      micromachining processes. The carboxylic acid groups of one polymer-poly(acrylic
      acid) (PAA)-can be transformed by reversible ion-exchange from water-soluble (Na+
      counterion) to water-insoluble (Ca2+ counterion) forms. The use of PAA and
      dextran polymers as sacrificial materials is a useful technique for the
      fabrication of microstructures: Examples include metallic structures formed by
      the electrodeposition of nickel, and freestanding, polymeric structures formed by
      photolithography.

PMID- 17193517
TI  - Organic-dye-coupled magnetic nanoparticles encaged inside thermoresponsive PNIPAM
      Microcapsules.
AB  - We present a new approach for the fabrication of thermoresponsive polymer
      microcapsules with mobile magnetic cores that undergo a volume phase-transition
      upon changing the temperature and are collected under an external magnetic field.
      We have prepared organic/inorganic composite microspheres with a well-defined
      core-shell structure that are composed of a crosslinked poly(N
      isopropylacrylamide) (PNIPAM) shell and silica cores dotted centrally by
      magnetite nanoparticles. Since the infiltration of template-decomposed products
      is dependent on the permeability of PNIPAM shells triggered by changes of
      exterior temperature, the silica layer sandwiched between the magnetic core and
      the PNIPAM shell was quantitatively removed to generate PNIPAM microcapsules with
      mobile magnetic cores by treatment with aqueous NaOH solution. For development of
      the desired multifunctional microcapsules, modification of the unetched silica
      surface interiors can be realized by treatment with a silane coupling agent
      containing functional groups that can easily bind to catalysts, enzymes, or
      labeling molecules. Herein, fluorescein isothiocyanate (FITC), which is a common
      organic dye, is attached to the insides of the mobile magnetic cores to give
      PNIPAM microcapsules with FITC-labeled magnetic cores. In this system, it can be
      expected that an extension of the functionalization of the cavity properties of
      smart polymer microcapsules is to immobilize other target molecules onto the
      mobile cores in order to introduce other desired functions in the hollow cage.

PMID- 17193518
TI  - Simple synthesis of hierarchically ordered mesocellular mesoporous silica
      materials hosting crosslinked enzyme aggregates.
AB  - Hierarchically ordered mesocellular mesoporous silica materials (HMMS) were
      synthesized using a single structure-directing agent. The mesocellular pores are
      synthesized without adding any pore expander; the pore walls are composed of SBA
      15 type mesopores. Small-angle X-ray scattering revealed the presence of uniform
      pore structures with two different sizes. Using HMMS as a nanoscopic template,
      hierarchically ordered mesocellular mesoporous carbon (HMMC) and polymer (HMMP)
      materials were synthesized. HMMS was used as a host for enzyme immobilization. To
      improve the retention of enzymes in HMMS, we adsorbed enzymes, and then employed
      crosslinking using glutaraldehyde (GA). The resulting crosslinked enzyme
      aggregates (CLEAs) show an impressive stability with extremely high enzyme
      loadings. For example, 0.5 g alpha-chymotrypsin (CT) could be loaded in 1 g of
      silica with no activity decrease observed with rigorous shaking over one month.
      In contrast, adsorbed CT without GA treatment resulted in a lower loading, which
      further decreased due to continuous leaching of adsorbed CT under shaking. The
      activity of crosslinked CT aggregates in HMMS was approximately 10 times higher
      than that of the adsorbed CT, which represents a 74-fold increase in activity per
      unit weight of HMMS due to higher CT loading.

PMID- 17193519
TI  - Ionogel-templated synthesis and organization of anisotropic gold nanoparticles.
AB  - Photochemical reduction of tetrachloroaurate (AuCl4-) ions in the highly
      constrained aqueous domains of a nanostructured ionogel template, formed via self
      assembly of the ionic liquid 1-decyl-3-methylimidazolium chloride (C10mim+Cl-) in
      water, results in the formation of anisotropic gold nanoparticles with a variety
      of sizes and morphologies, which include previously unattainable trigonal
      prismatic nanorods. Unexpectedly, small-angle X-ray scattering studies of the Au
      ionogel composite reveal that the in situ formation of the nanoparticles
      increases the mesoscopic order of the ionogel, which results in its conversion to
      a near-monodomain structure. The findings demonstrate that nanostructured, ionic
      liquid-based gels can be used to template the formation of new nanoparticle
      morphologies with technologically important optical, electronic, and catalytic
      properties. It may also be possible to design soft templates that permit the
      fabrication of highly ordered nanoparticle array-hydrogel composites, thereby
      enabling control and tuning of the collective properties of the encapsulated
      nanoparticles.

PMID- 17193523
TI  - Nanotech insight.

PMID- 17193524
TI  - Electromechanical transducers at the nanoscale: actuation and sensing of motion
      in nanoelectromechanical systems (NEMS).
AB  - Electromechanical devices are rapidly being miniaturized, following the trend in
      commercial transistor electronics. Miniature electromechanical devices--now with
      dimensions in the deep sub-micrometer range--are envisioned for a variety of
      applications as well as for accessing interesting regimes in fundamental physics.
      Among the most important technological challenges in the operation of these
      nanoelectromechanical systems (NEMS) are the actuation and detection of their sub
      nanometer displacements at high frequencies. In this Review, we shall focus on
      this most central concern in NEMS technology: realization of electromechanical
      transducers at the nanoscale. The currently available techniques to actuate and
      detect NEMS motion are introduced, and the accuracy, bandwidth, and robustness of
      these techniques are discussed.

PMID- 17193525
TI  - Solid-state pyrolyses of metal phthalocyanines: a simple approach towards
      nitrogen-doped CNTs and metal/carbon nanocables.

PMID- 17193527
TI  - Electrochemical growth of organic conducting microcrystals of tetrathiafulvalene
      bromide.

PMID- 17193526
TI  - Double-template synthesis of CdS nanotubes with strong electrogenerated
      chemiluminescence.

PMID- 17193528
TI  - Preparation of ultrathin free-standing porous metal films.

PMID- 17193530
TI  - The cytotoxicity of metal-encapsulating carbon nanocapsules.

PMID- 17193529
TI  - Low-temperature synthesis of highly crystalline TiO2 nanocrystals and their
      application to photocatalysis.

PMID- 17193532
TI  - Hybrid microstructures from aligned carbon nanotubes and silica particles.

PMID- 17193531
TI  - Nanotube network transistors from peptide-wrapped single-walled carbon nanotubes.

PMID- 17193533
TI  - Endowing a ferritin-like cage protein with high affinity and selectivity for
      certain inorganic materials.

PMID- 17193534
TI  - Nanoscale patterning of protein using electron beam lithography of organosilane
      self-assembled monolayers.

PMID- 17193535
TI  - Formation of ferroelectric perovskite nanostructure patterns using latex sphere
      monolayers as masks: an ambient gas pressure effect during pulsed laser
      deposition.

PMID- 17193536
TI  - Cellular uptake and toxicity of Au55 clusters.

PMID- 17193537
TI  - Sensitive detection of proteins using difunctional DNA-gold nanoparticles.

PMID- 17193538
TI  - Construction of dithiol-based nanostructures by a layer-exchange process.

PMID- 17193539
TI  - Molecular boxes on a molecular printboard: encapsulation of anionic dyes in
      immobilized dendrimers.
AB  - Fifth-generation poly(propylene imine) dendrimers, modified with 64 apolar
      adamantyl groups, have been immobilized on cyclodextrin host monolayers
      ("molecular printboards") on glass by supramolecular microcontact printing. The
      immobilized dendrimers retain their guest-binding properties and function as
      "molecular boxes" that can be filled with fluorescent dye molecules from
      solution. Alternatively, part of the immobilized dendrimers were filled with dye
      molecules by cross-microcontact printing while the remaining, empty dendrimers
      were filled with a different dye from solution, resulting in alternating patterns
      of dye molecules. In addition, we demonstrate that encapsulation of dyes in
      immobilized dendrimers is reversible: immobilized molecular boxes can be filled
      with a dye, emptied, and subsequently refilled with a different dye.

PMID- 17193540
TI  - Thermally driven interfacial dynamics of metal/oxide bilayer nanoribbons.
AB  - Solid-solid interfacial processes greatly affect the performance of electronic
      and composite materials, but probing the dynamics of buried interfaces is
      challenging and often involves lengthy or invasive sample preparation. We show
      that bilayer nanoribbons-made here of tin dioxide and copper-are convenient
      structures for observing as-made interfaces as they respond to changing
      temperature in a transmission electron microscope (TEM). At low temperatures
      (<200 degrees C), differential thermal expansion causes the bilayers to bend when
      heated or cooled, with the motion determined by the extent of Cu-SnO(2) epitaxy.
      At higher temperatures, we are able to watch-in real time and with nanometer
      resolution-a progression of grain growth, interdiffusion, island formation, solid
      state chemical reactions, and melting. This novel TEM geometry is readily
      applicable to other nanoribbon/coating combinations and is well suited to
      observing interfacial phenomena driven thermally or by the application of
      mechanical, electrical, or magnetic forces.

PMID- 17193541
TI  - Novel ultrananocrystalline diamond probes for high-resolution low-wear
      nanolithographic techniques.
AB  - A hard, low-wear probe for contact-mode writing techniques, such as dip-pen
      nanolithography (DPN), was fabricated using ultrananocrystalline diamond (UNCD).
      Molding within anisotropically etched and oxidized pyramidal pits in silicon was
      used to obtain diamond tips with radii down to 30 nm through growth of UNCD films
      followed by selective etching of the silicon template substrate. The probes were
      monolithically integrated with diamond cantilevers and subsequently integrated
      into a chip body obtained by metal electroforming. The probes were characterized
      in terms of their mechanical properties, wear, and atomic force microscopy
      imaging capabilities. The developed probes performed exceptionally well in DPN
      molecular writing/imaging mode. Furthermore, the integration of UNCD films with
      appropriate substrates and the use of directed microfabrication techniques are
      particularly suitable for fabrication of one- and two-dimensional arrays of
      probes that can be used for massive parallel fabrication of nanostructures by the
      DPN method.

PMID- 17193542
TI  - Gram-scale synthesis of soluble, near-monodisperse gold nanorods and other
      anisotropic nanoparticles.
AB  - An aqueous surfactant-based colloidal chemical method is reported for the
      synthesis of anisotropic noble-metal nanoparticles on the milligram to multigram
      scale. Fine control of the nucleation-growth kinetics and rodlike micelle-induced
      breaking of symmetry at the early stage of particle growth are responsible for
      high-quality anisotropic nanoparticles. Near-monodisperse gold and silver
      nanorods, spheroids, nanowires, platelets, or cubes of 4-50 nm dimension and
      controllable aspect ratio can be prepared. The method may also be extended to
      semiconductor systems.

PMID- 17193543
TI  - Unconventional gallium oxide nanowires.
AB  - Zigzag and helical beta-Ga(2)O(3) one-dimensional nanostructures were produced by
      thermal evaporation of gallium oxide in the presence of gallium nitride. High
      resolution TEM analysis indicates that each individual zigzag nanostructure has a
      periodic arrangement of three distinct blocks: two structurally perfect blocks
      mirrored with respect to each other on the (002) plane, and one stacking-fault
      rich block sandwiched between them. In a zigzag nanostructure, the growth
      orientation of a beta-Ga(2)O(3) crystal changes alternately in three blocks. The
      zigzag nanostructure as a whole has the [001] axial direction. In addition to
      zigzag nanostructures, single-crystalline helical nanowires were also obtained.

PMID- 17193544
TI  - Self-assembly and crystallization behavior of mesoporous, crystalline HfO2 thin
      films: a model system for the generation of mesostructured transition-metal
      oxides.
AB  - Mesoporous thin films of crystalline hafnium oxide were fabricated by evaporation
      induced self-assembly in combination with sol-gel processing, followed by a
      suitable post heat-treatment procedure to initiate the crystallization. A novel
      type of block-copolymer template was used as structure-directing agent, which
      generated a distorted cubic arrangement of spherical mesopores, the size of which
      could be quantified by suitable techniques, such as ellipsometry-porosimetry,
      small-angle X-ray scattering, and atomic force microscopy. Detailed insights into
      the nature of the crystallization process of mesostructured hafnium oxide were
      obtained by temperature-dependent, in situ X-ray scattering experiments. These
      investigations revealed that crystallization takes place, within the confinement
      of the mesostructure, as a solid-solid transition from a dehydrated, amorphous
      form of hafnium oxide. The study suggests that one main benefit of the novel
      template results from the ability of the polymer to stabilize the mesostructure
      of amorphous hafnium oxide up to 400-450 degrees C.

PMID- 17193549
TI  - Silicon nanotubes.

PMID- 17193550
TI  - Near-edge X-ray absorption fine structure spectroscopy as a tool for
      investigating nanomaterials.
AB  - We have demonstrated near-edge X-ray absorption fine structure (NEXAFS)
      spectroscopy as a particularly useful and effective technique for simultaneously
      probing the surface chemistry, surface molecular orientation, degree of order,
      and electronic structure of carbon nanotubes and related nanomaterials.
      Specifically, we employ NEXAFS in the study of single-walled carbon nanotube and
      multi-walled carbon nanotube powders, films, and arrays, as well as of boron
      nitride nanotubes. We have focused on the advantages of NEXAFS as an exciting,
      complementary tool to conventional microscopy and spectroscopy for providing
      chemical and structural information about nanoscale samples.

PMID- 17193551
TI  - Metal and metal oxide nanoparticles in chemiresistors: does the nanoscale matter?
AB  - Sensor technology is one of the most important key technologies of the future
      with a constantly increasing number of applications, both in the industrial and
      in the private sectors. More and more gas sensors are used for the control of
      technical processes, in environment monitoring, healthcare, and automobiles.
      Consequently, the development of fast and sensitive gas sensors with small cross
      sensitivity is the subject of intense research, propelled by strategies based on
      nanoscience and -technology. Established systems can be improved and novel sensor
      concepts based on bottom-up approaches show that the sensor properties can be
      controlled by molecular design. This Review highlights the recent developments
      and reflects the impact of nanoscience on sensor technology.

PMID- 17193552
TI  - TiO2 nanofibers and core-shell structures prepared using mesoporous molecular
      sieves as templates.

PMID- 17193553
TI  - UV/Vis spectroelectrochemical evidence of rectification of quantized charging in
      monolayer-protected gold cluster films.

PMID- 17193554
TI  - Nanoindentation-induced disappearance of a room-temperature coulomb blockade in
      single-walled carbon nanotubes.

PMID- 17193555
TI  - Fabrication of ZnO nanoplate-nanorod junctions.

PMID- 17193556
TI  - Nanoengineering in echinoderms: the emergence of morphology from nanobricks.

PMID- 17193557
TI  - C60-assisted growth of gold nanowires using a stepped graphite surface as
      template.

PMID- 17193558
TI  - Additive patterning of conductors and superconductors by solution stamping
      nanolithography.

PMID- 17193559
TI  - Substrate-friendly synthesis of metal oxide nanostructures using a hotplate.

PMID- 17193560
TI  - Realization of a silicon nanowire vertical surround-gate field-effect transistor.

PMID- 17193561
TI  - Vertically aligned carbon nanofiber arrays: an advance toward electrical-neural
      interfaces.

PMID- 17193562
TI  - Multiwalled carbon nanotubes with molybdenum dioxide nanoplugs--new chemical
      nanoarchitectures by electrochemical modification.

PMID- 17193563
TI  - Design of self-assembling peptide nanotubes with delocalized electronic states.

PMID- 17193564
TI  - A fluorophore-based bio-barcode amplification assay for proteins.

PMID- 17193565
TI  - Self-assembly of carbon-nanotube-based single-electron memories.
AB  - We demonstrate the wafer-scale integration of single-electron memories based on
      carbon nanotube field-effect transistors (CNFETs) using a process based entirely
      on self assembly. First, a "dry" self-assembly step based on chemical vapor
      deposition (CVD) allows the growth and connection of CNFETs. Next, a "wet" self
      assembly step is used to attach a single 30-nm-diameter gold bead in the nanotube
      vicinity via chemical functionalization. The bead is used as the memory storage
      node while the CNFET operating in the subthreshold regime acts as an electrometer
      exhibiting exponential gain. Below 60 K, the transfer characteristics of gold
      CNFETs show highly reproducible hysteretic steps. Evaluation of the capacitance
      confirms that these current steps originate from the controlled storage of single
      electrons with a retention time that exceeds 550 s at 4 K.

PMID- 17193566
TI  - Beaklike SnO2 nanorods with strong photoluminescent and field-emission
      properties.
AB  - Beaklike SnO2 nanorods were synthesized by a vapor-liquid-solid approach using Au
      as a catalyst. The nanorods grow along the [10 1] direction and the beak is
      formed by switching the growth direction to [1 12] through controlling the growth
      conditions at the end of the synthesis. The photoluminescence (PL) spectrum of
      the nanorods exhibits visible light emission with a peak at 602 nm. The field
      emission (FE) properties of the nanorods have been measured to exhibit a turn-on
      field of 5.8 V microm(-1). A comparative study of FE measurements between SnO2
      nanorods with uniform diameters and these beaklike nanorods suggests that the
      shape and curved tips are important factors in determining the FE properties.

PMID- 17193567
TI  - Segmented Pt/Ru, Pt/Ni, and Pt/RuNi nanorods as model bifunctional catalysts for
      methanol oxidation.
AB  - Five-segment (Pt-Ru-Pt-Ru-Pt, Pt-Ni-Pt-Ni-Pt, and Pt-RuNi-Pt-RuNi-Pt) nanorods
      with the same overall rod length and the same total Pt segment length were
      prepared by sequential electrodeposition of the metals into the pores of
      commercially available anodic aluminum oxide (AAO) membranes. Field-emission
      scanning electron microscopy (FESEM) showed that the nanorods were about 210 nm
      in diameter and about 1.5 microm in length. The alternating Pt and oxophilic
      metal(s) segments could be easily differentiated in backscattered-electron
      images. X-ray diffraction (XRD) analysis of the nanorods indicated that Pt and Ni
      were polycrystalline with fcc structures, Ru was hcp, and the co-deposited RuNi
      adopted the nickel fcc structure with some negative shifts in the Bragg angles.
      The chemical states of Pt, Ru, and Ni on the nanorod surface were assayed by X
      ray photoelectron spectroscopy (XPS), and the presence of Pt(0), Pt(II), Pt(IV),
      Ru(0), Ru(VI), Ni(0), and Ni(II) was observed. The nanorods were catalytically
      active for the room-temperature electrooxidation of methanol in acidic solutions.
      The relative rates of reaction showed the Pt-RuNi pair sites as having the lowest
      overpotential to dissociate water, the highest catalytic activity in methanol
      oxidation, and the strongest CO-tolerance in the potential window employed. The
      use of segmented nanorods with identifiable Pt-oxophilic metal(s) interfaces
      removes many of the ambiguities in the interpretation of experimental data from
      conventional alloy catalysts, thereby enabling a direct comparison of the
      activities of various types of pair sites in methanol oxidation.

PMID- 17193569
TI  - Extracellular biosynthesis of magnetite using fungi.
AB  - The development of synthetic processes for oxide nanomaterials is an issue of
      considerable topical interest. While a number of chemical methods are available
      and are extensively used, the collaborations are often energy intensive and
      employ toxic chemicals. On the other hand, the synthesis of inorganic materials
      by biological systems is characterized by processes that occur at close to
      ambient temperatures and pressures, and at neutral pH (examples include
      magnetotactic bacteria, diatoms, and S-layer bacteria). Here we show that
      nanoparticulate magnetite may be produced at room temperature extracellularly by
      challenging the fungi, Fusarium oxysporum and Verticillium sp., with mixtures of
      ferric and ferrous salts. Extracellular hydrolysis of the anionic iron complexes
      by cationic proteins secreted by the fungi results in the room-temperature
      synthesis of crystalline magnetite particles that exhibit a signature of a
      ferrimagnetic transition with a negligible amount of spontaneous magnetization at
      low temperature.

PMID- 17193568
TI  - Biocatalytically induced formation of cupric ferrocyanide nanoparticles and their
      application for electrochemical and optical biosensing of glucose.
AB  - The enzymatically controlled growth of cupric ferrocyanide nanoparticles in the
      presence of glucose oxidase, its ferricyanide electron acceptor, and copper ions
      is described. The biocatalytically stimulated growth of these nanoparticles on
      the surface of carbon-paste electrodes results in an amplified electrochemical
      detection of the glucose substrate. This concept can readily be expanded for
      monitoring a wide range of biocatalytic processes involving the ferricyanide
      electron acceptor.

PMID- 17193574
TI  - Monitoring and analyzing nonlinear dynamics in atomic force microscopy.

PMID- 17193570
TI  - Heterotetramers formed by an S-layer-streptavidin fusion protein and core
      streptavidin as a nanoarrayed template for biochip development.
AB  - Based on the S-layer protein SbpA of Bacillus sphaericus CCM 2177, an S-layer
      streptavidin fusion protein was constructed. After heterologous expression,
      isolation of the fusion protein, and refolding, functional heterotetramers were
      obtained that had retained the ability to recrystallize into the square-lattice
      structure on plain gold chips and on gold chips precoated with secondary cell
      wall polymer (SCWP), which is the natural anchoring molecule for the S-layer
      protein in the bacterial cell wall. Monolayers generated by recrystallization of
      heterotetramers on plain gold chips or on gold chips precoated with thiolated
      SCWP were exploited for the binding of biotinylated oligonucleotides (30-mers).
      Hybridization experiments with complementary fluorescently labeled
      oligonucleotides carrying one mismatch or no mismatch (both 15-mers) were
      performed and evaluated with surface-plasmon-field-enhanced fluorescence
      spectroscopy. For surfaces generated by the recrystallization of heterotetramers
      on SCWP-coated gold chips, a detection limit of 1.57 pM could be determined,
      whereas for surfaces obtained by direct recrystallization of heterotetramers on
      plain gold chips, a detection limit of 8.2 pM was found. Measuring the
      association and dissociation processes of oligonucleotides carrying no mismatch
      led to a dissociation constant of K(D)=6.3 x 10(-10) m, whereas for
      oligonucleotides carrying one mismatch a dissociation constant of K(D)=7.9 x 10(
      9) m was determined. This finding was confirmed by measuring the whole Langmuir
      isotherm, which resulted in a dissociation constant of K(D)=2.6 x 10(-8) m.

PMID- 17193575
TI  - Monofunctional gold nanoparticles prepared via a noncovalent-interaction-based
      solid-phase modification approach.

PMID- 17193576
TI  - Site-selective integration of monolayer-protected inorganic nanoparticles onto
      surface monolayer templates by a solvent-induced lift-off process.

PMID- 17193577
TI  - Electroactive silica nanoparticles for biological labeling.

PMID- 17193579
TI  - Continuous analyte sensing with magnetic nanoswitches.

PMID- 17193578
TI  - Apoferritin-templated synthesis of metal phosphate nanoparticle labels for
      electrochemical immunoassay.

PMID- 17193580
TI  - Selective nanoscale positioning of ferritin and nanoparticles by means of target
      specific peptides.

PMID- 17193581
TI  - Complementary symmetry silicon nanowire logic: power-efficient inverters with
      gain.

PMID- 17193583
TI  - Facile synthesis of poly(3,4-ethylenedioxythiophene) nanofibers from an aqueous
      surfactant solution.

PMID- 17193582
TI  - Metallothioneins initiate semiconducting nanoparticle cellular toxicity.

PMID- 17193584
TI  - Efficient proteolysis system: a nanozeolite-derived microreactor.

PMID- 17193585
TI  - Carbon nanotubes encapsulated in wormlike hollow silica shells.

PMID- 17193586
TI  - Layered hydrogen-bonded nucleotide-functionalized CdS nanoparticles for
      photoelectrochemical applications.

PMID- 17193587
TI  - Biomimetic synthesis of wurtzite ZnO nanowires possessing a mosaic structure.

PMID- 17193588
TI  - Functionalized carbon nanotubes: synthesis of meltable and amphiphilic
      derivatives.

PMID- 17193589
TI  - Attachment of streptavidin to beta-cyclodextrin molecular printboards via
      orthogonal host-guest and protein-ligand interactions.
AB  - Streptavidin (SAv) is attached to beta-cyclodextrin (beta-CD) self-assembled
      monolayers (SAMs) via orthogonal host-guest and SAv-biotin interactions. The
      orthogonal linkers consist of a biotin functionality for binding to SAv and
      adamantyl functionalities for host-guest interactions at beta-CD SAMs. SAv
      complexed to excess monovalent linker in solution and then attached to a beta-CD
      SAM could be removed by rinsing with a 10 mM beta-CD solution. When SAv was
      attached to the beta-CD SAM via the divalent linker, it was impossible to remove
      SAv from the surface by the same rinsing procedure. This is interpreted by
      assuming that two SAv binding pockets are oriented towards the beta-CD SAM
      resulting in (labile) divalent and (stable) tetravalent beta-CD-adamantyl
      interactions for the mono- and divalent linkers, respectively. This was confirmed
      by experiments at varying beta-CD concentrations. When the [linker]/[SAv] ratio
      is reduced, a clear trend in the divalent-linker case is seen: the less linker
      the more protein could be removed from the surface. It is proven that the
      orthogonality of the binding motifs and the stability of the divalent linker at
      the beta-CD SAM allows the stepwise assembly of the complex at the beta-CD SAM by
      first adsorbing the linker, followed by SAv. This stepwise assembly allows the
      controlled heterofunctionalization of surface-immobilized SAv.

PMID- 17193590
TI  - Highly crystalline WO3 thin films with ordered 3D mesoporosity and improved
      electrochromic performance.
AB  - WO3 thin layers with nanometer-scale periodicity were prepared by evaporation
      induced self-assembly (EISA) using a novel amphiphilic block-copolymer template
      (poly(ethylene-co-butylene)-block-poly(ethylene oxide)). The evolution of the
      mesoporous ordered network and the crystallinity of the framework were monitored
      by 2D-SAXS, WAXS, SEM, XPS, and porosimetry. By annealing the films, the pore
      wall crystallinity is adjusted between fully amorphous and highly crystalline
      without mesostructural degradation. Thus, the crystalline-film framework is
      composed of phase-pure monoclinic WO3 nanoparticles (12-14 nm in size).
      Furthermore, heat treatment transforms the originally spherical mesopores into
      ellipsoids, resulting in a unidirectionally shrunken, but still well-defined and
      fully accessible bcc mesopore architecture. The influence of mesoporosity and
      crystallinity on electrochemical/electrochromic characteristics was addressed by
      monitoring electrochemical features and the absorption changes during Li
      insertion/extraction (repetitive potentiostatic cycling). Both the amorphous and
      crystalline mesoporous films possess electrochromic response times on the order
      of only seconds, which are attributable to the facilitated insertion of guest
      ions due to shortening of the diffusion path lengths. Also, the
      insertion/extraction reversibility of crystalline WO3 layers with 3D mesoporosity
      is improved compared to amorphous ones and reaches values close to 100%.

PMID- 17193591
TI  - Fungi use efficient algorithms for the exploration of microfluidic networks.
AB  - Fungi, in particular, basidiomycetous fungi, are very successful in colonizing
      microconfined mazelike networks (for example, soil, wood, leaf litter, plant and
      animal tissues), a fact suggesting that they may be efficient solving agents of
      geometrical problems. We therefore evaluated the growth behavior and optimality
      of fungal space-searching algorithms in microfluidic mazes and networks. First,
      we found that fungal growth behavior was indeed strongly modulated by the
      geometry of microconfinement. Second, the fungus used a complex growth and space
      searching strategy comprising two algorithmic subsets: 1) long-range directional
      memory of individual hyphae and 2) inducement of branching by physical
      obstruction. Third, stochastic simulations using experimentally measured
      parameters showed that this strategy maximizes both survival and biomass
      homogeneity in microconfined networks and produces optimal results only when both
      algorithms are synergistically used. This study suggests that even simple
      microorganisms have developed adequate strategies to solve nontrivial geometrical
      problems.

PMID- 17193594
TI  - Adventures in multivalency, the Harry S. Fischer memorial lecture CMR 2005;
      Evian, France.
AB  - This review discusses multivalency in the context of drug discovery, specifically
      the discovery of new diagnostic imaging and related agents. The aim is to draw
      attention to the powerful role that multivalency plays throughout research
      involving molecular biology, in general, and much of biochemically targeted
      contrast agent research, in particular. Two examples from the author's laboratory
      are described. We created small (approximately 5 kDa) peptide 'dimers' composed
      of two different, chemically linked peptides. The monomer peptides both bound to
      the same target protein with K(d) approximately 100 s nM, while the heterodimers
      had sub-nM K(d) values. Biological activity was evident in the heterodimers where
      none or very little existed in homodimers, monomers or monomer mixtures. Two
      different tyrosine kinases (KDR and C-Met) and four peptide families produced
      consistent results: multivalent heterodimers were uniquely different. The second
      example begins with making two micron ultrasound bubbles coated with the peptide,
      TKPPR (a Tuftsin antagonist) as a negative control for bubbles targeted with
      angiogenesis target-binding peptides. Unexpected binding of a 'negative' control,
      (TKPPR)-targeted bubble to endothelial cells expressing angiogenesis targets, led
      to the surprising result that TKPPR, only when multimerized, binds avidly,
      specifically and actively to neuropilin-1, a VEGF co-receptor. VEGF is the
      primary stimulator of angiogenesis. Tuftsin is a small peptide (TKPR) derived
      from IgG that binds to macrophages during inflammation, and has been studied for
      over 30 years. The receptor has never been cloned. The results led to new
      conclusions about Tuftsin, neuropilin-1 and the purpose, up to now unknown, of
      exon 8 in VEGF. Multivalency can be used rationally to solve practical problems
      in drug discovery. When targeting larger structures, multivalency is frequently
      unavoidable, and can lead to unpredictable and useful biochemical information, as
      well as to new drug candidates.

PMID- 17193595
TI  - Catalytic effects of apoferritin interior surface residues on water proton
      exchange in lanthanide complexes.

PMID- 17193597
TI  - Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities
      prevent the cells acting as 'sponges' of Gd3+ ions.
AB  - MR-labeling of cells may be carried out by adding a Gd-based contrast agent to
      the incubation media. The amount of gadolinium internalized in HTC and C6 cells
      upon incubation with Gd-DTPA-BMA is circa one order of magnitude higher than
      those found with Gd-DTPA, Gd-DOTA and Gd-HPDO3A, respectively. The comparison of
      relaxometric and mass spectrometry determinations allows us to establish that
      only a minor fraction of intact Gd-DTPA-BMA is internalized into the cells.
      Moreover the binding/uptake behavior shown by Gd-DTPA-BMA resembles that found
      when GdCl(3) is added to the incubation medium. We suggest that the lower
      stability of Gd-DTPA-BMA is responsible for a shift in the dissociation
      equilibrium that results in the net transfer of Gd(3+) ions on the cell membrane
      followed by a slower internalization process. The transmetallation process is
      mediated by components of the incubation media, among which a dominant role is
      represented by phosphate anions. The uptake of Gd(3+) ions is clearly reflected
      in the drastic decrease of cell viability observed for cells labeled with Gd-DTPA
      BMA.

PMID- 17193596
TI  - Specific E-selectin targeting with a superparamagnetic MRI contrast agent.
AB  - Targeting of the endothelial inflammatory adhesion molecule E-selectin by
      magnetic resonance imaging (MRI) was performed with a superparamagnetic contrast
      agent in the context of in vitro and in vivo models of inflammation. The specific
      contrast agent was obtained by grafting a synthetic mimetic of sialyl Lewis(x)
      (sLe(x)), a natural ligand of E-selectin expressed on leukocytes, on the dextran
      coating of ultrasmall particles of iron oxide (USPIO). This new contrast agent,
      called USPIO-g-sLe(x), was tested, in vitro, on cultured human umbilical vein
      endothelial cells (HUVECs) stimulated to express inflammatory adhesion molecules,
      and in vivo, on a mouse model of hepatitis. In vitro, HUVECs were stimulated with
      the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and were
      then incubated with USPIO-g-sLe(x) or ungrafted USPIO. In vivo, hepatitis was
      induced on NMRI mice by injection of concanavalin A (Con A). USPIO-g-sLe(x) and
      ungrafted USPIO were injected intravenously. In vitro results showed an extensive
      retention of USPIO-g-sLe(x) on TNF-alpha stimulated HUVECs. Image intensity and
      R(2) measurements performed on T(2)-weighted MR images demonstrated a
      significantly higher binding of USPIO-g-sLe(x) on stimulated HUVECs. In vivo,
      USPIO are known to pass through the fenestrae of the liver and to be captured by
      Kupffer cells, inducing a loss of signal intensity on T(2)-weighted MR images.
      Unexpectedly, when injected to Con A-treated mice, USPIO-g-sLe(x) induced a
      significantly lower attenuation of liver signal intensity than USPIO or USPIO-g
      sLe(x) injected to healthy mice, or USPIO injected to Con A-treated mice,
      suggesting that the specific contrast media is retained extracellularly by an
      interaction with E-selectin overexpressed on the vascular endothelium. Both in
      vitro and in vivo results therefore indicate that USPIO-g-sLe(x) is recognizing
      endothelial E-selectin. USPIO-g-sLe(x) is thus well suited for the MRI diagnosis
      of inflammation and for the in vitro evaluation of endothelial cells activation.

PMID- 17193599
TI  - International Contrast Media Research Symposium, Evian, France, 11 - 16 October
      2005. Abstracts.

PMID- 17193598
TI  - First in vivo MRI assessment of a self-assembled metallostar compound endowed
      with a remarkable high field relaxivity.
AB  - {Fe[Gd(2)bpy(DTTA)(2)(H(2)O)(4)](3)}(4-) is a self-assembled, metallostar
      structured potential MRI contrast agent, with six efficiently relaxing Gd(3+)
      centres confined into a small molecular space. Its proton relaxivity is
      particularly remarkable at very high magnetic fields (r(1) = 15.8 mM(-1) s(-1) at
      200 MHz, 37 degrees C, in H(2)O). Here we report the first in vivo MRI
      feasibility study, complemented with dynamic gamma scintigraphic imaging and
      biodistribution experiments using the (153)Sm-enriched compound. Comparative MRI
      studies have been performed at 4.7 T in mice with the metallostar and the small
      molecular weight contrast agent gadolinium(III)-1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetate ([Gd(DOTA)(H(2)O)](-) = GdDOTA). The metallostar was well
      tolerated by the animals at the concentrations of 0.0500 (high dose) and 0.0125
      (low dose) mmol Gd kg(-1) body weight; (BW). The signal enhancement in the
      inversion recovery fast low angle shot (IR FLASH) images after the high-dose
      metallostar injection was considerably higher than after GdDOTA injection (0.1
      mmol Gd kg(-1) BW), despite the higher dose of the latter. The high-dose
      metallostar injection resulted in a greater drop in the spin-lattice relaxation
      time (T(1)), as calculated from the inversion recovery true fast imaging with
      steady-state precession (IR TrueFISP) data for various tissues, than the GdDOTA
      or the low dose metallostar injection. In summary, these studies have confirmed
      that the approximately four times higher relaxivity measured in vitro for the
      metallostar is retained under in vivo conditions. The pharmacokinetics of the
      metallostar was found to be similar to that of GdDOTA, involving fast renal
      clearance, a leakage to the extracellular space in the muscle tissue and no
      leakage to the brain. As expected on the basis of its moderate molecular weight,
      the metallostar does not function as a blood pool agent. The dynamic gamma
      scintigraphic studies performed in Wistar rats with the metallostar compound
      having (153)Sm enrichment also proved the renal elimination pathway. The
      biodistribution experiments are in full accordance with the MR and scintigraphic
      imaging. At 15 min post-injection the activity is primarily localized in the
      urine, while at 24 h post-injection almost all radioactivity is cleared from
      tissues and organs.

PMID- 17193685
TI  - Gd-enhanced MR images of substrates other than water.
AB  - This communication reports the dramatic relaxation enhancements that can be
      obtained upon the interaction of substrates like lactate, trifluorolactate and
      inorganic phosphate with the paramagnetic GdDO3A agent. This occurs thanks to the
      formation of kinetically labile ternary complexes in which the substrate nuclei
      are in close proximity to the paramagnetic center. It is demonstrated that
      heteronuclear (13)C, (19)F and (31)P-MR images can be obtained from phantoms
      containing the substrate in the millimolar concentration range.

PMID- 17193686
TI  - Kinetic analysis of hyaluronidase activity using a bioactive MRI contrast agent.
AB  - One of the attractions of molecular imaging using 'smart' bioactive contrast
      agents is the ability to provide non-invasive data on the spatial and temporal
      changes in the distribution and expression patterns of specific enzymes. The
      tools developed for that aim could potentially also be developed for functional
      imaging of enzyme activity itself, through quantitative analysis of the rapid
      dynamics of enzymatic conversion of these contrast agents. High molecular weight
      hyaluronan, the natural substrate of hyaluronidase, is a major antiangiogenic
      constituent of the extracellular matrix. Degradation by hyaluronidase yields low
      molecular weight fragments, which are proangiogenic. A novel contrast material,
      HA-GdDTPA-beads, was designed to provide a substrate analog of hyaluronidase in
      which relaxivity changes are induced by enzymatic degradation. We show here a
      first-order kinetic analysis of the time-dependent increase in R(2) as a result
      of hyaluronidase activity. The changes in R(2) and the measured relaxivity of
      intact HA-GdDTPA-beads (r(2B)) and HA-GdDTPA fragments (r(2D)) were utilized for
      derivation of the temporal drop in concentration of GdDTPA in HA-GdDTPA-beads as
      the consequence of the release of HA-GdDTPA fragments. The rate of dissociation
      of HA-GdDTPA from the beads showed typical bell-shaped temperature dependence
      between 7 and 36 degrees C with peak activity at 25 degrees C. The tools
      developed here for quantitative dynamic analysis of hyaluronidase activity by MRI
      would allow the use of activation of HA-GdDTPA-beads for the determination of the
      role of hyaluronidase in altering the angiogenic microenvironment of tumor micro
      metastases.

PMID- 17193687
TI  - MRI tumor characterization using Gd-GlyMe-DOTA-perfluorooctyl-mannose-conjugate
      (Gadofluorine M), a protein-avid contrast agent.
AB  - The rationale and objectives were to define the MRI tumor-characterizing
      potential of a new protein-avid contrast agent, Gd-GlyMe-DOTA-perfluorooctyl
      mannose-conjugate (Gadofluorine M; Schering AG, Berlin, Germany) in a chemically
      induced tumor model of varying malignancy. Because of the tendency for this agent
      to form large micelles in water and to bind strongly to hydrophobic sites on
      proteins, it was hypothesized that patterns of dynamic tumor enhancement could be
      used to differentiate benign from malignant lesions, to grade the severity of
      malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05 mmol Gd
      kg(-1), was administered intravenously to 28 anesthetized rats that had developed
      over 10 months mammary tumors of varying degrees of malignancy as a consequence
      of intraperitoneal administration of N-ethyl-N-nitrosourea (ENU), 45-250 mg kg(
      1). These tumors ranged histologically from benign fibroadenomas to highly
      undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed
      kinetically using a two-compartment tumor model to generate estimates of
      fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*)
      and an endothelial transfer coefficient (K(PS)) for this contrast agent. Tumors
      were examined microscopically for tumor type, degree of malignancy (Scarff-Bloom
      Richardson score) and location of necrosis. Eighteen tumor-bearing rats were
      successfully imaged. MRI data showed an immediate strong and gradually increasing
      tumor enhancement. K(PS) and fEV*, but not fPV obtained from tumors correlated
      significantly (p < 0.05) with the SBR tumor grade, r = 0.65 and 0.56,
      respectively. Estimates for K(PS) and fEV* but not fPV were significantly lower
      in a group consisting of benign and low-grade malignant tumors compared with the
      group of less-differentiated high-grade tumors (1.61 +/- 0.64 vs 3.37 +/- 1.49, p
      < 0.01; 0.45 +/- 0.17 vs 0.78 +/- 0.24, p < 0.01; and 0.076 +/- 0.048 vs 0.121 +/
      0.088, p = 0.24, respectively). It is concluded that the protein-avid MRI
      contrast agent Gadofluorine M enhances tumors of varying malignancy depending on
      the tumor grade, higher contrast agent accumulation for more malignant lesions.
      The results show potential utility for differentiating benign and low-grade
      malignant lesions from high-grade cancers.

PMID- 17193688
TI  - Impact of rigidification on relaxometric properties of a tricyclic
      tetraazatriacetic gadolinium chelate.
AB  - A constrained derivative of Gd-PCTA12, Gd-cyclo-PCTA12, in which one ethylene
      bridge connecting two nitrogen atoms of the triamine block is replaced by a
      cyclohexylene bridge, was synthesized and the impact of rigidification was
      studied by comparing the physicochemical and relaxometric properties of both
      gadolinium MRI contrast agents, Gd-PCTA12 and Gd-cyclo-PCTA12. The new complex
      has higher proton relaxivity than the parent compound (r(1) = 6.1 s(-1) mM(-1) at
      20 MHz and 310 K). The rigidification of the PCTA12 scaffold proved to have no
      impact on the inertness towards transmetallation by endogenous ions such as
      Zn(2+). Moreover, for both contrast agents, the relaxivity was not quenched by
      endogenous anions. The oxygen-17 NMR study and the NMRD profile demonstrated that
      the rigidification of the PCTA scaffold had no impact on the electronic
      relaxation of Gd-cyclo-PCTA12. However, the rigidity of this complex induced an
      acceleration of the exchange rate of the inner-sphere water molecules as a result
      of steric crowding around the gadolinium ion. The value of tau(M) (310) thus
      approached the optimal value required to attain high relaxivity once the chelate
      is immobilized by covalent or non-covalent binding to macromolecules.

PMID- 17193691
TI  - Use of intra-articular carbon dioxide and air for MR arthrography: a feasibility
      study.
AB  - During animal experiments, carbon dioxide (CO(2)) and air were used as a novel
      contrast agent for direct magnetic resonance arthrography (MRAr). MRAr was
      performed after injection of CO(2) and air in the knee joints of two pigs. MR
      images of phantoms containing air, CO(2) and nitrogen were compared. After intra
      articular injection, both present as a signal void on various sequences and
      permit sharp delineation of cartilage and other adjacent structures. Despite the
      potential for artefact generation, only a slight susceptibility artefact was seen
      after injection of CO(2) and air. In phantom experiments, air, CO(2) and nitrogen
      demonstrated identical slight regular susceptibility artefacts at the phantom
      margins. CO(2) MRAr can yield high contrast between cartilage, ligaments and
      synovium relative to the joint compartment. Therefore, this technique might be
      useful as an investigational method for the evaluation of cartilage surface
      lesions and possibly as an alternative contrast agent for clinical use.

PMID- 17193689
TI  - Comparative study of the physicochemical properties of six clinical low molecular
      weight gadolinium contrast agents.
AB  - This paper compares the physicochemical properties of six low molecular weight
      clinical complexes of gadolinium studied under identical experimental conditions.
      Magnevist, Dotarem, Omniscan, ProHance, MultiHance and Gadovist were investigated
      by oxygen-17 relaxometry at different temperatures and by proton relaxometry at
      various magnetic fields, temperatures and media [pure water, zinc(II)-containing
      aqueous solutions and HSA-containing solutions]. Osmolality, viscosity and
      stability versus transmetallation by zinc(II) ions were added for a more
      comprehensive description. The relaxivities of the clinical formulations as
      measured in water are similar in the imaging magnetic field region, with a
      slightly better performance for MultiHance. This can be explained by a shorter
      distance between the hydrogen nuclei of the water molecule bound to the Gd(3+)
      ion and this paramagnetic centre. In contrast to the open-chain complexes, all
      macrocyclic systems (Dotarem, ProHance and Gadovist) are insensitive to
      transmetallation by zinc ions. The stability of the open-chain complexes with
      respect to transmetallation depends on the chemical structure of the ligand, with
      a better stability for MultiHance. The presence of human serum albumin has no
      significant effect on the proton relaxivity of Magnevist, Dotarem, Omniscan,
      ProHance and Gadovist but markedly increases the relaxivity of MultiHance because
      of a non-covalent interaction with the protein. As a result, the relaxivity of
      MultiHance in HSA-containing media of fixed concentration decreases with
      increasing concentration of the contrast agent.

PMID- 17193693
TI  - Single-cell detection by gradient echo 9.4 T MRI: a parametric study.
AB  - Recent studies have shown that cell migration can be monitored in vivo by
      magnetic resonance imaging after intracellular contrast agent incorporation. This
      is due to the dephasing effect on proton magnetization of the local magnetic
      field created by a labelled cell. Anionic iron oxide nanoparticles (AMNP) are
      among the most efficient and non-toxic contrast agents to be spontaneously taken
      up by a wide variety of cells. Here we measured the iron load and magnetization
      of HeLa tumour cells labelled with AMNP, as a function of the external magnetic
      field. High-resolution gradient echo 9.4 T MRI detected individual labelled
      cells, whereas spin echo sequences were poorly sensitive. We then conducted a
      systematic study in order to determine the gradient echo sequence parameters
      (echo time, cell magnetization and resolution) most suitable for in vivo
      identification of single cells.

PMID- 17193692
TI  - Tumor imaging in small animals with a combined micro-CT/micro-DSA system using
      iodinated conventional and blood pool contrast agents.
AB  - X-ray based micro-computed tomography (CT) and micro-digital subtraction
      angiography (DSA) are important non-invasive imaging modalities for following
      tumorogenesis in small animals. To exploit these imaging capabilities further,
      the two modalities were combined into a single system to provide both
      morphological and functional data from the same tumor in a single imaging
      session. The system is described and examples are given of imaging implanted
      fibrosarcoma tumors in rats using two types of contrast media: (a) a new
      generation of blood pool contrast agent containing iodine with a concentration of
      130 mg/mL (Fenestratrade mark VC, Alerion Biomedical, San Diego, CA, USA) for
      micro-CT and (b) a conventional iodinated contrast agent (Isovue(R)-370 mg/mL
      iodine, trademark of Bracco Diagnostics, Princeton, NJ, USA) for micro-DSA. With
      the blood pool contrast agent, the 3D vascular architecture is revealed in
      exquisite detail at 100 microm resolution. Micro-DSA images, in perfect
      registration with the 3D micro-CT datasets, provide complementary functional
      information such as mean transit times and relative blood flow through the tumor.
      This imaging approach could be used to understand tumor angiogenesis better and
      be the basis for evaluating anti-angiogenic therapies.

PMID- 17193695
TI  - How to determine free Gd and free ligand in solution of Gd chelates. A technical
      note.
AB  - Gd(III) chelates are often used as reporting probes in magnetic resonance imaging
      applications. Their use relies on the assumption that their high stability
      ensures against the release of free ligand and free Gd(3+) ions, which are both
      highly toxic to living systems. The presence of free Gd(3+) ions may have a
      profound effect on the contrast in the MR image as they may form highly hydrated,
      macromolecular complexes endowed with very high relaxivity thus providing
      erroneous information on the extent of the contrast effect induced by the given
      reporting probe. Although the stability of a given complex may be high enough,
      the complexation step could not have been completed. Therefore any Gd complex
      preparation has to be carefully checked for the content of free ligand and free
      metal ions. Herein the currently used procedures that allow an assessment of the
      amounts of free metal ions and free ligand in a solution of a given Gd complex
      are described in detail.

PMID- 17193696
TI  - A new type of susceptibility-artefact-based magnetic resonance angiography: intra
      arterial injection of superparamagnetic iron oxide particles (SPIO) A Resovist in
      combination with TrueFisp imaging: a feasibility study.
AB  - The goal of this study was to evaluate the use of super paramagnetic particles of
      iron oxide (SPIO) as a dark blood contrast agent, in combination with a bright
      blood steady-state free precession sequence for magnetic resonance angiography
      (MRA), in an animal model. The original concentration of the SPIO of 500 mmol
      Fe/l and dilutions to 250, 125, 60, 30, 10 and 5 mmol Fe/l were intra-arterially
      injected into the aorta of a pig. Then the dilution of 10 mmol Fe/l was chosen
      for repeated intra-arterial injections into two pigs. During these intra-arterial
      SPIO injections MR images were acquired with a 1.5 T scanner. Signal intensity
      measurements were performed in the aorta. The signal-to-noise ratio during SPIO
      bolus passage was significantly less than during baseline conditions (Fisher's F
      ratio 159.8, p < 0.005) or the recovery signal-to-noise ratio (Fisher's F-ratio
      144.6, p < 0.005). Also, confirmation of flow distal to the catheter-tip position
      was possible. The use of SPIO as a dark blood agent in combination with a bright
      blood MR imaging sequence is feasible. Temporary loss of intraluminal signal
      occurs due to local decrease of the signal because of induction of local
      inhomogeneities after mixture the present blood and SPIO solution. It provides
      immediate information about blood flow distal to the catheter and is a
      potentially useful to guide intravascular MR-interventional procedures.

PMID- 17193698
TI  - L-amino acid load to enhance PET differentiation between tumor and inflammation:
      an in vitro study on (18)F-FET uptake.
AB  - Labeled amino acids (AA) are tumor tracers for use in nuclear medecine. O-(2
      [(18)F]fluoroethyl)-L-tyrosine (FET) is transported by the L-system, known to
      function as an exchanger. In vitro utilization of FET, after a preload or prior
      to an afterload of non radioactive L-amino acids, was evaluated in order to
      measure the potential effects of AA content on the distinction between tumor and
      inflammatory lesions. Cellular uptake of FET was studied on rat osteosarcoma
      cells (ROS 17/2.8) and human leukocytes, initially loaded with nonradioactive L
      tyrosine or L-methionine. FET efflux was evaluated from cells loaded with
      nonradioactive L-phenylalanine after tracer uptake. ROS 17/2.8 showed a higher
      sensitivity to preload and afterload effects on cellular FET content as compared
      with the leukocytes. We conclude that preload with L-tyrosine, prior to the
      administration of FET, may be a potential procedure to improve PET
      differentiation between tumor and inflammatory lesions.

PMID- 17193699
TI  - [Postoperative delirium].

PMID- 17193700
TI  - Positive end-expiratory pressure (PEEP) ventilation for liver transplant
      patients: the evolving story.

PMID- 17193697
TI  - An HPLC/mass spectrometry platform for the development of multimodality contrast
      agents and targeted therapeutics: prostate-specific membrane antigen small
      molecule derivatives.
AB  - The production of disease-targeted agents requires the covalent conjugation of a
      targeting molecule with a contrast agent or therapeutic, followed by purification
      of the product to homogeneity. Typical targeting molecules, such as small
      molecules and peptides, often have high charge-to-mass ratios and/or
      hydrophobicity. Contrast agents and therapeutics themselves are also diverse, and
      include lanthanide chelates for MRI, (99m)Tc chelates for SPECT, (90)Y chelates
      for radiotherapy, (18)F derivatives for PET, and heptamethine indocyanines for
      near-infrared fluorescent optical imaging. We have constructed a general-purpose
      HPLC/mass spectrometry platform capable of purifying virtually any targeted agent
      for any modality. The analytical sub-system is composed of a single dual-head
      pump that directs mobile phase to either a hot cell for the purification of
      radioactive agents or to an ES-TOF MS for the purification of nonradioactive
      agents. Nonradioactive agents are also monitored during purification by ELSD,
      absorbance and fluorescence. The preparative sub-system is composed of columns
      and procedures that permit rapid scaling from the analytical system. To
      demonstrate the platform's utility, we describe the preparation of five small
      molecule derivatives specific for prostate-specific membrane antigen (PSMA): a
      gadolinium derivative for MRI, indium, rhenium and technetium derivatives for
      SPECT, and an yttrium derivative for radiotherapy. All five compounds are derived
      from a highly anionic targeting ligand engineered to have a single nucleophile
      for N-hydroxysuccinimide-based conjugation. We also describe optimized
      column/mobile phase combinations and mass spectrometry settings for each class of
      agent, and discuss strategies for purifying molecules with extreme charge and/or
      hydrophobicity. Taken together, our study should expedite the development of
      disease-targeted, multimodality diagnostic and therapeutic agents.

PMID- 17193701
TI  - Bibliography. Current world literature. Diagnostics and techniques.

PMID- 17193702
TI  - Patient safety alert. Collaborative model works in Knoxville RRT initiative.

PMID- 17193703
TI  - Retraction statement.

PMID- 17193704
TI  - The ntrC gene of Agrobacterium tumefaciens C58 controls glutamine synthetase
      (GSII) activity, growth on nitrate and chromosomal but not Ti-encoded arginine
      catabolism pathways.
AB  - The ntrC locus of Agrobacterium tumefaciens C58 has been cloned using the
      Azorhizobium sesbaniae ORS571 ntrC gene as a DNA hybridization probe. Transposon
      Tn5 mutagenesis of the cloned ntrC locus was carried out and one Tn5 insertion
      within the region of highest DNA homology with A. sesbaniae ORS571 ntrC was used
      for gene replacement of the wild-type C58 ntrC gene. The A. tumefaciens ntrC::Tn5
      mutant was found to be unable to grow on nitrate as sole nitrogen (N) source, to
      lack glutamine synthetase (GSII) activity and to be unable to use arginine (or
      ornithine) as sole N source, unless the Ti-encoded arginine catabolism pathway
      was induced with small amounts of nopaline. Thus the A. tumefaciens ntrC
      regulatory gene is essential for (transcriptional) activation of the GSII and
      nitrate reductase genes, as well as for the chromosomal but not the Ti-borne
      arginine catabolism pathways.

PMID- 17193705
TI  - Rapid splicing and stepwise processing of a transcript from the psbB operon in
      tobacco chloroplasts: determination of the intron sites in petB and petD.
AB  - Expression of the psbB gene cluster in tobacco chloroplasts has been studied.
      This cluster contains the genes for the 51 kDa chlorophyll a apoprotein (psbB)
      and the 10 kDa phosphoprotein (psbH) of the photosystem II, and cytochrome b6
      (petB) and subunit IV (petD) of the cytochrome b/f complex in this order.
      Northern blot hybridization and reverse transcription analyses have revealed that
      petB and petD contain single introns and the psbB gene cluster is transcribed as
      a single polycistronic unit. The primary transcript seems to be spliced very
      rapidly and then processed into several small RNA species. The exact splice sites
      have been located by cDNA sequencing. The transcriptional initiation site of the
      psbB operon has been determined by S1 mapping with in vitro capped chloroplast
      RNA. The stepwise processing of chloroplast RNA precursors is discussed.

PMID- 17193706
TI  - Pleiotropic soybean mutants defective in both urease isozymes.
AB  - Two new soybean [Glycine max (L.) Merr. cv. Williams] loci, designated Eu2 and
      Eu3, were identified in which ethyl methanesulfonate (EMS)-induced mutation
      eliminated urease activity. These loci showed no linkage to each other or to the
      "Sun-Eul" locus described in the accompanying paper (Meyer-Bothling and Polacco
      1987). Unlike sun (seed urease-null) mutations those at Eu2 and Eu3 affected both
      urease isozymes: the embryo-specific (seed) and the ubiquitous (leaf) urease. The
      eu2/eu2 mutant had no leaf activity and 0.6% normal seed activity. Two mutant Eu3
      alleles were recovered, eu3-e1 and Eu3-e3. The eu3-e1/eu3-e1 genotype lacked both
      activities while Eu3-e3/Eu3-e3 had coordinately reduced leaf (0.1%) and seed
      (0.1%) activities. Only the Eu3-e3 mutation showed partial dominance, yielding
      about 5%-10% normal activity for each urease in the heterozygous state. Each
      homozygous mutant contained normal levels of embryo-specific urease mRNA and
      protein subunit, both of normal size. However, urease polymerization was aberrant
      in all three mutants. In all cases where urease could be measured, it was found
      to be temperature sensitive and, in addition, the embryo-specific urease of Eu3
      e3/Eu3-e3 had an altered pH dependence. These mutants may be defective in a
      urease maturation function common to both isozymes as suggested by the normal
      levels of urease gene product, coordinately (or nearly so) reduced urease isozyme
      activities, temperature sensitivity in both ureases (Eu3-e3) and the non-linkage
      of Eu2 and Eu3 to the locus encoding embryo-specific urease (Sun-Eul). Ubiquitous
      urease activity is reduced in mutant seed coat and callus culture as well as in
      leaf and cotyledon tissue. No mutant callus utilized urea (5 to 10 nM0 as sole
      nitrogen source. However, all mutant cell lines tolerated normally toxic levels
      of urea (25 to 250 mM) added to medium containing KNO3/NH4No3 as nitrogen source.
      Urea thus may be used in cell culture as a selection agent for phenotypes either
      lacking or regaining an active ubiquitous urease.

PMID- 17193707
TI  - Mutational analysis of the embryo-specific urease locus of soybean.
AB  - By a non-destructive urease screen of M2 soybean (Glycine max [L.] Merr. cv.
      Williams) seeds, four true-breeding mutants (n4, n6, n7 and n8) were recovered
      which lack most (n6, n8) or all (n4, n7) embryo-specific urease activity. This
      trait was due to a single, recessive lesion at the Sun (seed urease-null) locus
      identified earlier in an exotic germplasm (PI 229324, Itachi). All sun mutants
      produced normal ubiquitous urease, the low abundance isozyme found in all soybean
      tissues examined. Tight mutants n4 and n7 accumulated no detectable embryo
      specific urease protein or mRNA; n6 and n8 accumulated normal or near normal
      levels of urease mRNA but had seed urease protein levels approximately 5% and
      .05%, respectively, of the progenitor. Mutant n8 appeared to produce a low level
      of fully active urease (approximately 0.7% activity level, approximately 0.5%
      protein level) while n6 produced a higher level of an altered, nearly inactive
      urease (.0.09% activity level, approximately 5% protein level). Urease
      alterations in n6 were manifested by its increased temperature sensitivity and
      variation in aggregation state and pH preference. Thus, mutations in the Sun
      locus affected both the level and the nature of the embryo-specific urease gene
      products indicating that Sun encodes the embryo-specific urease. We reported
      earlier that the Eul locus, which controls the aggregation state of the embryo
      specific urease, is on mep unit from Sun and that the Eul allele is cis to sun is
      not expressed (Kloth et al. 1987). That the level of urease gene product, its
      aggregation state and other enzyme properties can be affected by induced sun
      mutations, suggests that the Eul and sun alleles are at the same locus.

PMID- 17193708
TI  - Selective and accurate initiation of transcription at the T-DNA promoter in a
      soluble chromatin extract from wheat germ.
AB  - An in vitro assay system was developed for accurate transcription of the octopine
      type T-DNA gene in a wheat germ extract. The system consists of the protein
      fraction extracted from the chromatin of wheat germ, substrates and exogenously
      added DNA. Specific initiation at the promoter was determined by a combination of
      primer extension analysis and size analysis of the transcripts synthesized from
      DNA templates of various molecular sizes. Synthesis of the transcripts was
      sensitive to alpha-amanitin. With truncated DNA templates containing the intact
      promoter and the proximal transcribing region of several hundred base pairs of
      the T-DNA, run-off transcripts of the expected size originating at the authentic
      promoter were synthesized together with relatively small amounts of prematurely
      terminated RNA molecules. On fractionation of the chromatin protein extract by
      DEAE-cellulose column chromatography, the fraction eluted with 0.3 M KCl showed
      no activity by itself for specific initiation of transcription at the promoter by
      RNA polymerase II. The activity was however restored by adding the fraction
      eluted with 0.15 M KCl, and the reconstituted RNA polymerase fraction correctly
      initiated transcription at the authentic promoter.

PMID- 17193709
TI  - Agrobacterium rhizogenes T-DNA genes capable of inducing hairy root phenotype.
AB  - Segments of the TL-DNA of the agropine type Ri plasmid pRi 1855 encompassing
      single and groups of open-reading frames were cloned in the Ti plasmid-derived
      binary vector system Bin 19. Leaf disc infections on Nicotiana tabacum led to
      transformed plants, some of which showed typical hairy root phenotypes, such as
      the wrinkled leaf morphology, excessive and partially non geotropic root systems
      and the ability of leaf explants to differentiate roots in a hormone-free culture
      medium. Particularly interestingly, most of these traits were shown by plants
      transformed with a TL-DNA segment encompassing the single ORF 11, corresponding
      to the rolB locus. Hairy root can be induced by this latter T-DNA segment on
      wounded stems of tobacco plants; hairy root induction on carrot discs requires,
      on the contrary, a more complex complement of TL-DNA genes.

PMID- 17193710
TI  - Molecular analysis of paramutant plants of Antirrhinum majus and the involvement
      of transposable elements.
AB  - Paramutation is observed when the Antirrhinum majus lines 44 and 53 are crossed.
      These two lines both have insertions at the nivea locus, which encodes chalcone
      synthase (chs). The allele niv-53 carries the transposable element Tam1 in the
      promoter region of the chs gene; niv-44 carries the element Tam2 within the gene.
      The Tam1 element has previously been extensively characterised. Here the Tam2
      element is further characterised, and the arrangement of the nivea locus in
      paramutant plants is analysed. The complete sequence of Tam2, and that of a
      partial cDNA complementary to it, have been determined. The cDNA is probably
      transcribed from a different copy of Tam2 from that present at the nivea locus,
      and does not encode a functional protein. Genomic Southerns of F1 plants from the
      53/44 cross show that no major rearrangements are consistently associated with
      paramutation at the nivea locus of A. majus. The isolation from a paramutant
      plant arising from a 53/44 cross of an allele (niv-4432) resulting from the
      excision of Tam2 is reported. The excision of Tam2 resulted in a 32 bp deletion
      of chs gene sequences. Plants homozygous for the new niv-4432 allele have white
      flowers and are still paramutagenic, demonstrating that Tam2 need not be present
      at the nivea locus for paramutation to occur. Different interactions between Tam1
      and Tam2 are discussed, and a possible model for paramutation is presented.

PMID- 17193711
TI  - Genetic control of cell proliferation in female germ line cells of Drosophila:
      mosaic analysis of five discless mutations.
AB  - The 'discless' mutations are zygotic lethals of Drosophila melanogaster with
      lethal phase at the larva/pupa boundary. They have been shown to identify genes
      whose functions are required for cell proliferation in the soma. We analysed
      mosaic females (generated by pole cell transplantation or by the dominant female
      sterile technique) with mutant germ line and normal soma and concluded that (1)
      the discless genes are required for the proliferation of the female germ line
      cells. (2) The discless genes are expressed during oogenesis and (3) as suggested
      by indirect evidence, the maternally provided gene products are necessary for
      cell proliferation in the embryo. It is suggested, that the same sets of genes
      control proliferation in the soma, germ line and-through the maternal effect
      embryos in Drosophila.

PMID- 17193712
TI  - Cloning of DNA fragments complementary to tobacco nitrate reductase mRNA and
      encoding epitopes common to the nitrate reductases from higher plants.
AB  - Messenger RNAs encoding the nitrate reductase apoenzyme from tobacco can be
      translated in a cell-free system. Poly(A)+ mRNA fractions from the 23-32 S area
      of a sucrose gradient were used to build a cDNA library in the expression vector
      gt11 with an efficiency of cloning of approximately 10(4) recombinants/ng mRNA.
      Recombinant clones were screened with a rabbit polyclonal antibody directed
      against the corn nitrate reductase, which cross reacts specifically with the
      nitrate reductases from dicotyledons. Among 240000 recombinant plaques, eight
      clones were isolated containing inserts of sizes ranging from 1.6 kb to 2.1 kb
      and sharing sequence homologies. Seven of these clones contained a common
      internal 1.6 kb EcoRI fragment. The identity of these clones was confirmed as
      follows. A fusion protein of 170 kDa inducible by IPTG and recognized by the
      rabbit nitrate reductase antibody was expressed by a lysogen derived from one of
      the recombinants. The antibodies binding the fused protein were eluted and shown
      to be inhibitory to the catalytic activity of tobacco nitrate reductase. Two
      monoclonal antibodies directed against nitrate reductase were also able to bind
      the hybrid protein. The 1.6 kb EcoRI fragment was sequenced by the method of
      Sanger. The open reading frame corresponding to a translational fusion with the 
      galactosidase coding sequence of the vector shared strong homology at the amino
      acid level with the heme-binding domain of proteins of the cytochrome b5
      superfamily and with human erythrocyte cytochrome b5 reductase. When the 1.6 kb
      EcoRI fragment was used as a probe for Northern blot experiments a signal
      corresponding to a 3.5 kb RNA was detected in tobacco and in Nicotiana
      plumbaginifolia mRNA preparations but no cross-hybridization with corn mRNAs was
      detected. The probe hybridized with low copy number sequences in genomic blots of
      tobacco DNA.

PMID- 17193713
TI  - A plasmid sequence from Rhizobium leguminosarum 300 contains homology to
      sequences near the octopine TL-DNA right border.
AB  - The DNA sequence from a Rhizobium leguminosarum 300 (RL300) plasmid that contains
      homology to the Tc-DNA of Agrobacterium tumefaciens is described. The RL300
      sequence has 78% homology to a 359 bp sequence in the Tc-DNA of pTi15955. The
      RL300 homology starts approximately 100 bp from the 24 bp border sequence of the
      TL-DNA and ends approximately 3 bp from an IS66 homolog in the Tc-DNA. An unusual
      feature of the RL300 homology is the presence of 81 bp direct repeats with Tc-DNA
      homology, separated by 201 bp. One end of each direct repeat has a 12 bp
      palindrome. Four cloned sequences of RL300 with homology to the T DNA region were
      hybridized to plasmid lysates of RL300 derivatives to determine the source of
      each plasmid. The sequenced homolog, originally on pRH228, was isolated from
      pRL7JI; the other 3 homologs were isolated from the transmissable plasmids pRL7JI
      (pRH235) and pRL8JI (pRH235 and pRH236).

PMID- 17193714
TI  - Isolation and characterization of Nicotiana plumbaginifolia nitrate reductase
      deficient mutants: genetic and biochemical analysis of the NIA complementation
      group.
AB  - Two hundred and eleven nitrate reductase-deficient mutants (NR-) were isolated
      from mutagenized Nicotiana plumbaginifolia protoplast cultures by chlorate
      selection and regenerated into plant. More than 40% of these clones were
      classified as cnx and presumed to be affected in the biosynthesis of the
      molybdenum cofactor, the remaining clones being classified as nia mutants. A
      genetic analysis of the regenerated plants confirmed this proportion of nia and
      cnx clones. All mutants regenerated were found to carry monogenic recessive
      mutations that impaired growth on nitrate as sole nitrogen source. Mutants
      propagated by grafting on N. tabacum systematically displayed a chlorotic leaf
      phenotype. This chlorosis was therefore related to the NR deficiency. The
      observation of leaves with NR- chlorotic sectors surrounded by NR+ wild-type
      tissues suggests that an NR deficiency is not corrected by diffusible factors.
      Periclinal chimeras between wild-type tobacco and the NR- graft were also
      observed. In this type of chimeric tissue chlorosis was no longer detectable when
      NR+ cells were in the secondmost (L2) layer, but was still detectable when NR-
      cells were in the secondmost layer. The genetic analysis of nia mutants revealed
      that they belong to a single complementation group. However three nia mutants
      were found to complement some of the other nia mutants. The apoenzyme of nitrate
      reductase was immunologically detected in several nia mutants but not in other
      members of this complementation group. Some of the nia mutants, although they
      were NR-, still displayed methylviologen-nitrate reductase activity at a high
      level. These data show that the nia complementation group corresponds to the
      structural gene of nitrate reductase. Some of the mutations affecting this
      structural gene result in the overproduction of an inactive nitrate reductase,
      suggesting a feedback regulation of the level of the apoenzyme in the wild type.

PMID- 17193715
TI  - Genetic analysis of the pelA-pelE cluster encoding the acidic and basic pectate
      lyases in Erwinia chrysanthemi EC16.
AB  - In Erwinia chrysanthemi (EC16) the clustered pelA and pelE genes encode an acidic
      (pI 4.2) and a basic (pI 10.0) pectate lyase (Pel), respectively. The pelA gene
      has been isolated on a 1.2 kb restriction fragment and the direction of
      transcription determined. DNA hybridization analysis showed that the pelE
      sequence shares DNA homology with pelA but not with pelB or pelC, two genes
      encoding other Pel species in EC16. Since Pel A and Pel E enzymes showed little
      similarity in terms of catalytic properties, it is proposed that pelA and pelE
      are duplicates which have highly diverged.

PMID- 17193718
TI  - On: sanity and madness.

PMID- 17193716
TI  - Direct response of Bradyrhizobium japonicum nifA-mediated nif gene regulation to
      cellular oxygen status.
AB  - The nifA genes of Klebsiella pneumoniae and Bradyrhizobium japonicum were
      constitutively expressed from the pBR329-derived chloramphenicol resistance
      promoter. The inserts of these nifA plasmid constructs were devoid of any other
      intact flanking genes. The nifA genes thus expressed led to a marked activation
      of a B. japonicum nifD-lacZ fusion under microaerobic conditions. Under aerobic
      growth conditions, however, activation was mediated only by the K. pneumoniae
      nifA gene but not by the B. japonicum nifA gene. This selective effect was
      observed in both the Escherichia coli as well as the B. japonicum backgrounds.
      Several lines of evidence suggest that in these experiments oxygen adversely
      affects B. japonicum nifA-dependent nif gene regulation at the post
      transcriptional level, probably even at the post-translational level, and that
      this effect does not require a nifL-like gene. Models are proposed in which
      oxygen inhibits the B. japonicum NifA protein either directly or indirectly via
      other cellular components involved in general protein oxidation pathways.

PMID- 17193717
TI  - Insertion of short poly d(A) d(T) sequences at recombination junctions in
      mitochondrial DNA of Podospora.
AB  - We have characterized the DNA sequences at recombination points in the
      mitochondrial DNA of two independent mitochondrial mutants of Podospora anserina.
      These sequences reveal the presence of foreign DNA at each recombination border,
      consisting of short stretches of A and T residues. We discuss the possible origin
      of this DNA and suggest the involvement of a reverse transcriptase activity.

PMID- 17193719
TI  - On: seeing and being seen.

PMID- 17193720
TI  - The gift that keeps on giving.

PMID- 17193721
TI  - Update on the management of pediatric acute promyelocytic leukemia.

PMID- 17193722
TI  - Eculizumab in paroxysmal nocturnal hemoglobinuria.

PMID- 17193723
TI  - Enoxaparin in elective percutaneous coronary intervention.

PMID- 17193724
TI  - Methaemoglobinaemia--out of the wash comes a blue baby.

PMID- 17193725
TI  - The hazards of watching football--are Australians at risk?
AB  - OBJECTIVE: To review whether watching football increases the population cardiac
      event risk in New South Wales. DESIGN: Analysis of hospital admissions for acute
      myocardial infarction, other cardiovascular disease, and other acute injuries at
      the time of two stressful sporting events in NSW in 2005: the Sydney Swans
      playing in the Australian Football League (AFL) Grand Final, and the Socceroos'
      penalty shoot-out in their World Cup qualifying match against Uruguay. RESULTS:
      There were no increases in any of the studied admission events at the time of, or
      in the days immediately following, these football matches. CONCLUSIONS:
      Australians appear to be resistant to acute stressors associated with watching
      sporting events, possibly due to higher rates of motivational deficiency disorder
      (MoDeD) than in European populations.

PMID- 17193727
TI  - Proliferating neural precursor cells as first step toward neuroregeneration in
      Huntington's disease?

PMID- 17193726
TI  - Xmas (brand substitution not permitted).
AB  - OBJECTIVE: To study drug prescribing by brand name versus generic name in an
      Australian teaching hospital. RESULTS: Overall, 53% of drugs were prescribed by
      brand name. Brand names were preferred when they were shorter and easier to
      remember and spell, when there was only one brand on the market, and when the
      brand name ended in an x. CONCLUSION: Doctors might be encouraged to prescribe
      generically if generic names were devised using the same principles marketers use
      for devising brand names.

PMID- 17193728
TI  - Webs, levers, and other metaphors for influence over policy change.

PMID- 17193729
TI  - Forcing pharmaceutical history into boxes.

PMID- 17193730
TI  - [Toward a history and anthropology of the iatrogenic effects of the "fight"
      against disease].

PMID- 17193731
TI  - [Malnutrition and low bone mineralisation in adults with cystic fibrosis].
AB  - With striking advances in its treatment, cystic fibrosis has turned into an adult
      condition. Respiratory complications and exocrine pancreatic insufficiency work
      together to cause malnutrition which reduces survival. The management of low bone
      mineralization (osteoporosis, osteomalacia) is necessary not only to limit growth
      failure in younger patients but still in adulthood. We received the literature on
      malnutrition and bone diseases in adults with cystic fibrosis.

PMID- 17193732
TI  - The converging forces of the global economy on welfare states worldwide are met
      with diverging forces at national and subnational levels.

PMID- 17193733
TI  - Health inequality remains a central concern in many developed nations.

PMID- 17193734
TI  - Chemistry and fate of simazine.
AB  - Simazine, first introduced in 1956, is a popular agricultural herbicide used to
      inhibit photosynthesis in broadleaf weeds and grasses. It is a member of the
      triazine family, and according to its physicochemical properties, it is slightly
      soluble in water, relatively nonvolatile, capable of partitioning into organic
      phases, and susceptible to photolysis. Sorption and desorption studies on its
      behavior in soils indicate that simazine does not appreciably sorb to minerals
      and has the potential to leach in clay and sandy soils. The presence of organic
      matter in soils contributes to simazine retention but delays its degradation. The
      primary sorptive mechanism of simazine to OM has been proposed to be via
      partitioning and/or by the interaction with functional groups of the sorbent.
      Farming practices directly influence the movement of simazine in soils as well.
      Tilled fields lower the runoff of simazine when compared to untilled fields, but
      tilling can also contribute to its movement into groundwater. Planting cover
      crops on untilled land can significantly reduce simazine runoff. Such practices
      are important because simazine and its byproducts have been detected in
      groundwater in The Netherlands, Denmark, and parts of the U.S. (California, North
      Carolina, Illinois, and Wisconsin) at significant concentrations. Concentrations
      have also been detected in surface waters around the U.S. and United Kingdom.
      Although the physicochemical properties of simazine do not support
      volatilization, residues have been found in the atmosphere and correlate with its
      application. Although at low concentrations, simazine has also been detected in
      precipitation in Pennsylvania (U.S.), Greece, and Paris (France). Abiotically,
      simazine can be oxidized to several degradation products. Although hydrolysis
      does not contribute to the dissipation of simazine, photolysis does. Microbial
      degradation is the primary means of simazine dissipation, but the process is
      relatively slow and kinetically controlled. Some bacteria and fungal species
      capable of utilizing simazine as a sole carbon and nitrogen source at a fast rate
      under laboratory conditions have been identified. Metabolism of simazine in
      higher organisms is via cytochrome P-450-mediated oxidation and glutathione
      conjugation.

PMID- 17193735
TI  - Ethanol production: energy, economic, and environmental losses.
AB  - The prime focus of ethanol production from corn is to replace the imported oil
      used in American vehicles, without expending more fossil energy in ethanol
      production than is produced as ethanol energy. In a thorough and up-to-date
      evaluation of all the fossil energy costs of ethanol production from corn, every
      step in the production and conversion process must be included. In this study, 14
      energy inputs in average U.S. corn production are included. Then, in the
      fermentation/distillation operation, 9 more identified fossil fuel inputs are
      included. Some energy and economic credits are given for the by-products,
      including dried distillers grains (DDG). Based on all the fossil energy inputs, a
      total of 1.43 kcal fossil energy is expended to produced 1 kcal ethanol. When the
      energy value of the DDG, based on the feed value of the DDG as compared to that
      of soybean meal, is considered, the energy cost of ethanol production is reduced
      slightly, to 1.28 kcal fossil energy input per 1 kcal ethanol produced. Several
      proethanol investigators have overlooked various energy inputs in U.S. corn
      production, including farm machinery, processing machinery, and the use of hybrid
      corn. In other studies, unrealistic, low energy costs were attributed to such
      inputs as nitrogen fertilizer, insecticides, and herbicides. Controversy
      continues concerning the energy and economic credits that should be assigned to
      the by-products. The U.S. Department of Energy reports that 17.0 billion L
      ethanol was produced in 2005. This represents only less than 1% of total oil use
      in the U.S. These yields are based on using about 18% of total U.S. corn
      production and 18% of cornland. Because the production of ethanol requires large
      inputs of both oil and natural gas in production, the U.S. is importing both oil
      and natural gas to produce ethanol. Furthermore, the U.S. Government is spending
      about dollar 3 billion annually to subsidize ethanol production, a subsidy of
      dollar 0.79/L ethanol produced. With the subsidy, plus the cost of production,
      the cost of ethanol is calculated to be dollar 1.21/L. The subsidy for a liter of
      ethanol is 45-times greater than the subsidy per liter of gasoline. The
      environmental costs associated with producing ethanol are significant but have
      been ignored by most investigators in terms of energy and economics. The negative
      environmental impacts on cropland, and freshwater, as well as air pollution and
      public health, have yet to be carefully assessed. These environmental costs in
      terms of energy and economics should be calculated and included in future ethanol
      analyses. General concern has been expressed about taking 18% of U.S. corn, and
      more in the future, to produce ethanol for burning in automobiles instead of
      using the corn as food for the many malnourished people in the world. The World
      Health Organization reports that more than 3.7 billion humans are currently
      malnourished in the world--the largest number ever in history.

PMID- 17193736
TI  - Arsenic behaviour from groundwater and soil to crops: impacts on agriculture and
      food safety.
AB  - High levels of As in groundwater commonly found in Bangladesh and other parts of
      Asia not only pose a risk via drinking water consumption but also a risk in
      agricultural sustainability and food safety. This review attempts to provide an
      overview of current knowledge and gaps related to the assessment and management
      of these risks, including the behaviour of As in the soil-plant system, uptake,
      phytotoxicity, As speciation in foods, dietary habits, and human health risks.
      Special emphasis has been given to the situation in Bangladesh, where groundwater
      via shallow tube wells is the most important source of irrigation water in the
      dry season. Within the soil-plant system, there is a distinct difference in
      behaviour of As under flooded conditions, where arsenite (AsIII) predominates,
      and under nonflooded conditions, where arsenate (AsV) predominates. The former is
      regarded as most toxic to humans and plants. Limited data indicate that As
      contaminated irrigation water can result in a slow buildup of As in the topsoil.
      In some cases the buildup is reflected by the As levels in crops, in others not.
      It is not yet possible to predict As uptake and toxicity in plants based on soil
      parameters. It is unknown under what conditions and in what time frame As is
      building up in the soil. Representative phytotoxicity data necessary to evaluate
      current and future soil concentrations are not yet available. Although there are
      no indications that crop production is currently inhibited by As, long-term risks
      are clearly present. Therefore, with concurrent assessments of the risks,
      management options to further prevent As accumulation in the topsoil should
      already have been explored. With regard to human health, data on As speciation in
      foods in combination with food consumption data are needed to assess dietary
      exposure, and these data should include spatial and seasonal variability. It is
      important to control confounding factors in assessing the risks. In a country
      where malnutrition is prevalent, levels of inorganic As in foods should be
      balanced against the nutritional value of the foods. Regarding agriculture, As is
      only one of the many factors that may pose a risk to the sustainability of crop
      production. Other risk factors such as nutrient depletion and loss of organic
      matter also must be taken into account to set priorities in terms of research,
      management, and overall strategy.

PMID- 17193738
TI  - Mercury content of hair in different populations relative to fish consumption.
AB  - Hair has been used in many studies as a bioindicator of mercury exposure for
      human populations. At the time of hair formation, mercury from the blood
      capillaries penetrates into the hair follicles. As hair grows approximately 1 cm
      each month, mercury exposure over time is recapitulated in hair strands. Mercury
      levels in hair closest to the scalp reflect the most recent exposure, while those
      farthest from the scalp are representative of previous blood concentrations.
      Sequential analyses of hair mercury have been useful for identifying seasonal
      variations over time in hair mercury content, which may be the result of seasonal
      differences in bioavailability of fish and differential consumption of
      piscivorous and herbivorous fish species. Knowledge of the relation between fish
      eating practices and hair mercury levels is particularly important for adequate
      mitigation strategies. Methyl mercury is well absorbed, and because the
      biological half-life is long, the body burden in humans may reach high levels.
      People who frequently eat contaminated seafood can acquire mercury concentrations
      that are potentially dangerous to the fetus in pregnant women. The dose-response
      relationships have been extensively studied, and the safe levels of exposure have
      tended to decline. Individual methyl mercury exposure is usually determined by
      analysis of mercury in blood and hair. The objective of the present review was to
      examine variations in hair mercury levels from different populations with respect
      to fish-eating practices.

PMID- 17193737
TI  - Health effects of arsenic, fluorine, and selenium from indoor burning of Chinese
      coal.
AB  - China's economy has developed rapidly in the last two decades, leading to an
      increase in energy consumption and consequently emissions from energy generation.
      Coal is a primary energy source in China because of its abundance and will
      continue to be used in the future. The dominance of coal in energy production is
      expected to result in increasing levels of exposure to environmental pollution in
      China. Toxic trace elements emitted during coal combustion are the main sources
      of indoor air pollution. They are released into the atmosphere mainly in the
      forms of fine ash and vapors and have the potential to adversely affect human
      health. Those trace elements, which volatilize during combustion, are hazardous
      air pollutants (HAPs) and are particularly rich in Chinese coals. Among the HAPs,
      arsenic (As), fluorine (F), and selenium (Se) have already been identified as
      pollutants that can induce severe health problems. In this review, the
      geochemical characteristics of As, F, and Se, including their concentration,
      distribution, and mode of occurrences in Chinese coal, are documented and
      discussed. Our investigations have confirmed the current As- and F-induced
      epidemics in Guizhou (Southwest China) and Se epidemic in Hubei (Northeast
      China). In this study, diagnostic symptoms of arseniasis, fluorosis, and
      selenosis are also illustrated.

PMID- 17193740
TI  - [Fluoride content of soft drinks produced in Poland].
AB  - Fluoride content of 81 commercial brands of soft drinks and bottled waters were
      determined using potentiometric method with ion selective electrode. In the
      beverages produced in the same factory fluoride level were similar. The
      connection between elevation of fluoride levels and ingredients of investigated
      products such as juice or cola extract was not found. However, in some samples of
      ice tea drinks containing the tea extract fluoride levels might have been raised
      up to 1.28 mg/l. Fluoride contents of beverages from 28 producers ranged from
      0.01 to 0.30 mg/l and only from 4 producers up to 0.60 mg/l. The highest level of
      fluoride (1.39 mg/l) has been determined in one sample of mineral water. In
      conclusion, ice tea beverages and certain mineral water, made and sold in Poland,
      may constitute an important source of fluoride in diet. Their consumption,
      particularly in case of children, must be controlled.

PMID- 17193739
TI  - Toxicology of 1,3-butadiene, chloroprene, and isoprene.
AB  - The diene monomers, 1,3-butadiene, chloroprene, and isoprene, respectively,
      differ only in substitution of a hydrogen, a chlorine, or a methyl group at the
      second of the four unsaturated carbon atoms in these linear molecules. Literature
      reviewed in the preceding sections indicates that these chemicals have important
      uses in synthesis of polymers, which offer significant benefits within modern
      society. Additionally, studies document that these monomers can increase the
      tumor formation rate in various organs of rats and mice during chronic cancer
      bioassays. The extent of tumor formation versus animal exposure to these monomers
      varies significantly across species, as well among strains within species. These
      studies approach, but do not resolve, important questions of human risk from
      inhalation exposure. Each of these diene monomers can be activated to
      electrophilic epoxide metabolites through microsomal oxidation reactions in
      mammals. These epoxide metabolites are genotoxic through reactions with nucleic
      acids. Some of these reactions cause mutations and subsequent cancers, as noted
      in animal experiments. Significant differences exist among the compounds,
      particularly in the extent of formation of highly mutagenic diepoxide
      metabolites, when animals are exposed. These metabolites are detoxified through
      hydrolysis by epoxide hydrolase enzymes and through conjugation with glutathione
      with the aid of glutathione S-transferase. Different strains and species perform
      these reactions with varying efficacy. Mice produce these electrophilic epoxides
      more rapidly and appear to have less adequate detoxification mechanisms than rats
      or humans. The weight of evidence from many studies suggests that the balance of
      activation versus detoxification offers explanation of differing sensitivities of
      animals to these carcinogenic actions. Other aspects, including molecular biology
      of the many processes that lead through specific mutations to cancer, are yet to
      be understood. Melnick and Sills (2001) compared the carcinogenic potentials of
      these three dienes, along with that of ethylene oxide, which also acts through an
      epoxide intermediate. From the number of tissue sites where experimental animal
      tumors were detected, butadiene offers greatest potential for carcinogenicity of
      these dienes. Chloroprene and then isoprene appear to follow in this order.
      Comparisons among these chemicals based on responses to external exposures are
      complicated by differences among studies and of species and tissue
      susceptibilities. Physiologically based pharmacokinetic models offer promise to
      overcome these impediments to interpretation. Mechanistic studies at the
      molecular level offer promise for understanding the relationships among
      electrophilic metabolites and vital genetic components. Significant improvements
      in minimization of industrial worker exposures to carcinogenic chemicals have
      been accomplished after realization that vinyl chloride caused hepatic
      angiosarcoma in polymer production workers (Creech and Johnson 1974; Falk et al.
      1974). Efforts continue to minimize disease, particularly cancer, from exposures
      to chemicals such as these dienes. Industry has responded to significant
      challenges that affect the health of workers through efforts that minimize plant
      exposures and by sponsorship of research, including animal and epidemiological
      studies. Governmental agencies provide oversight and have developed facilities
      that accomplish studies of continuing scientific excellence. These entities
      grapple with differences in perspective, objectives, and interpretation as
      synthesis of knowledge develops through mutual work. A major challenge remains,
      however, in assessment of significance of environmental human exposures to these
      dienes. Such exposure levels are orders of magnitude less than exposures studied
      in experimental or epidemiological settings, but exposures may persist much
      longer and may involve unknown but potentially significant sensitivities in the
      general population. New paradigms likely will be needed for toxicological
      evaluation of these human exposures, which are ongoing but as yet are not
      interpreted.

PMID- 17193741
TI  - [Occurrence of some pesticides residues in peppermint Mentha piperita L. in 2003
      2005].
AB  - The aim of this paper was to present occurrence of pesticides residues in
      peppermint Mentha Piperita in 2003-2005 and to estimate of their intakes by
      consumer. Gas chromatographic and spectroscopy methods were used. The most
      frequently found were chlorpyrifos residues (16% analysed samples) followed by
      terbacil (11%), dithiocarbamates (10%) and diazinon (5%). Residues in 14%
      analysed samples exceeded the European Union Maximum Residue Levels established
      for tea. Assuming consumption of peppermint on the level of 4.5 g (three bags)
      per day, short-term intake by adult and child consumer was a few times lower then
      Acceptable Daily Intake.

PMID- 17193743
TI  - [Contents of heavy metals, nitrate (V), and nitrate (III) in fruits of elderberry
      and black chokeberry depending on harvest site and vegetation period].
AB  - Lead, cadmium, nitrate V and nitrate III contents were determined in elderberry
      and black chokeberry fruits harvested in Lublin region. Samples were taken from
      areas that were potentially exposed and not exposed to pollution. Fruits analyzed
      in 2003 and 2004 harvested from area exposed to pollution were characterized by
      higher lead concentration (0.043-0.098 mg kg(-1) fresh mass and 0.048-0.081 mg
      kg(-1) fresh mass, respectively) than those collected from potentially not
      polluted area. Levels of tested metals in fruits harvested from both areas in
      2004 were fairly similar to those from 2003. However, cadmium content in all
      collected fruits from both areas (in both vegetation periods) appeared to be high
      and much exceeded its permissible value (0.03 mg kg(-1) fresh mass). Levels of
      nitrate V was low and similar in fruits harvested in both seasons from both areas
      not exceeding 3.4 mg kg(-1) fresh mass. Content of nitrate III was also low and
      oscillated within the range 0.68-0.89 mg kg(-1) fresh mass.

PMID- 17193742
TI  - [Selenium in mushrooms].
AB  - In the article are reviewed available data from the scientific literature on
      content as well as speciation of selenium in mainly edible mushrooms collected in
      Europe. Some species of the genus Albtrellus were found exceptionally rich in
      selenium, and relatively less are some representatives of the genus Boletus
      (especially Boletus eduilis), Macrolepiota, Agaricus or Ronmaria, while for many
      other is less than 1.0 mg/kg dry matters. Nevertheless, tha available database on
      selenium in higher edible mushrooms is not so great if considering the number of
      wild growing as well as cultivated species and their spread in space.

PMID- 17193744
TI  - [Acrylamide content in potato crisps in Poland].
AB  - The main source of acrylamide in the diet are thermally processed carbohydrate
      rich products, mainly those obtained from potatoes. Acrylamide is a substance
      with neurotoxic, genotoxic and carcinogenic properties. The International Agency
      for Research on Cancer classified it as a potential human carcinogen in 1994. The
      purpose of this study was to assess acrylamide content in 24 samples of crisps
      randomly collected in Poland in 2004. Acrylamide was determined in the form of
      brominated derivatives by gas chromatography coupled with mass spectrometry. The
      average acrylamide content in the crisp samples examined was 998 mg/kg of the
      product, ranging from 352 to 3647 microg/kg, depending on the type of the crisps.
      The factor determining the differences in acrylamide content in the product was
      also the manufacturer. The average content of acrylamide in the crisps produced
      by three different manufacturers (manufacturers 1-3) was ca. 600-900 microg/kg,
      and in the crisps produced by manufacturer 4 was ca. 3 times higher. Moreover,
      substantial differences were found between the same types of crisps produced by
      the same manufacturers but originating from different manufacturing batches. The
      results obtained suggest the effects of various technological processes and raw
      material types on the level of acrylamide in crisps.

PMID- 17193745
TI  - [Influence of the ozonation on the elimination of arsenic from natural mineral
      water intended for bottling].
AB  - Mineral water--hydrogen carbonat-calcium naturally sparkling water--containing
      arsenic in concentration above 0.01 mg/dm3 was ozonated. There was experimentally
      determined the optimal ozonation parameters: ozone dose, a duration of the
      process and of the contact between ozone and water, concentration of dissolved
      ozon in water. There was, moreover, determined an exceeding of ozone residual
      permissible in the obligatory regulations for bottled mineral waters.

PMID- 17193746
TI  - [Overall migartion testing with alternative fatty food simulants].
AB  - Overall migration from commercial samples of food plastics packaging into 95%
      ethanol and isooctane--the alternative fatty food simulants--was determined.
      Testing conditions--time and temperature of the contact of food packaging
      material with food simulants reflected real or predicted use of given packaging.
      The analytical methods according to European Standard EN 1186 were used. Test
      methods by filling the artiecles, total immersion, forming a pouch or using the
      cell were used for migration as appropriate to allow contact with liquid food
      simulant only this surface which will come into the contact with food during
      normal use of the product. The overall migration from the samples of the tested
      products into both food simulants (95% ethanol and iso-octane) was well below the
      limit (10 mg/dm2), except of the migration from plasticized PVC films which
      markedly exceeded above limit, showing that these films must not be used for
      packaging of food containing fat. Application of food simulants as a alternative
      to olive oil markedly shortens analytical procedure and reduces workload, both
      important in routine testing.

PMID- 17193747
TI  - A comparison of selected media and incubation temperatures for isolation of
      microscopic fungi from dried medicinal plants.
AB  - The study compared selected media and incubation temperatures for isolation of
      fungi from dried medicinal plants (chamomile, peppermint, lemon balm, St. John's
      wort and two herbal mixtures). The DG18 medium was found to be the most suitable
      for characterization of the mycoflora at 25 degrees C. The medium selection for
      37 degrees C was dependent on the species to be isolated. MEA + 40% sacharose and
      YpSs were found to be the best media for isolation of thermophilic and
      thermotolerant fungi from dried medicinal plants.

PMID- 17193748
TI  - [Microorganisms in operating room air--selected aspects].
AB  - Test results of total number of bacteria and fungi in air of operating rooms were
      presented. The investigation was performed during "warm season" of the year--from
      June to September. Concentration of bacteria and fungi in the air of operating
      rooms with and without air conditioning system are compared, as well between
      hospitals where continuous inspections and regulations of air conditioning
      systems are practiced and those where inspections and regulations were done
      periodically. Results from operating rooms with faulty air conditioning are
      presented separately.

PMID- 17193749
TI  - [The influence of diet and physical activity therapy on the body's composition of
      medium obesity women and men].
AB  - In 56 women and 15 men the efficiency of two weeks diet and physical activity
      therapy was evaluated. The following parameters before and after the therapy were
      measured: BM, BMI, LBM, WHR and the fat mass (FATkg and FAT%). The subjects were
      divided into four groups depending on sex: (group of men and group of women), and
      value of BMI (group of persons with BMI lower than 27 and group of persons with
      BMI higher than 27). Both, body mass, content of fat and BMI decreased in all
      groups after two weeks of therapy.

PMID- 17193750
TI  - Health workforce crisis--together, we can make a difference.

PMID- 17193751
TI  - Integration of disease surveillance in India: current scenario and future
      perspective.

PMID- 17193752
TI  - An assessment of rabies free status of the Island of Andaman, Nicobar and
      Lakshadweep: results of the WHO sponsored national multicentric rabies survey.
AB  - The Islands of Andaman and Nicobar and Lakshadweep have been reported to be
      rabies free from time immemorial. Recently, a survey of the islands of Andaman
      and Nicobar & Lakshadweep was done between July and August 2003 to assess their
      rabies free status. It was revealed that these islands continue to remain rabies
      free. However, in Andamans the increasing dog population, poor vigil on import of
      dogs and lack of laboratory surveillance for rabies posed a threat to this
      status. The Lakshadweep islands, which are free of dogs, however, faced a threat
      from the lack of vigil on the entry and presence of cats and poor surveillance
      for rabies in them.

PMID- 17193753
TI  - A study on intranatal care practices in a district of West Bengal.
AB  - A study was conducted at Birbhum district of West Bengal among mothers who
      delivered in last one year to generate area-specific community-based data on the
      proportion of home deliveries, assistance during conduction of delivery and the
      intranatal care practices followed in the district. A multistage 40 cluster
      sampling method was used to study 320 mothers in the district. 37.81% deliveries
      were conducted at home. About 25% deliveries were conducted by untrained birth
      attendants, unqualified practitioners or relatives and friends. In 85.13% of home
      deliveries, DDK was not used. 68.6% home deliveries were conducted on the floor
      without any clean covering sheet. Though a clean instrument was used to cut the
      cord in 86.78% of home deliveries, a clean cord tie was used in only 24.89%
      cases. In 36.36% home deliveries, something was applied on the cord stump. High
      proportion of deliveries assisted by untrained persons and high magnitude of
      faulty intranatal care practices observed in the study require urgent and
      appropriate intervention.

PMID- 17193754
TI  - Coronary risk factors in a rural community.
AB  - A cross-sectional health examination survey was carried out among a random sample
      of 406 people of 30 years and above from a rural community to investigate the
      prevalence of coronary heart disease risk factors. Prevalence of smoking and
      tobacco use was 16%, alcohol intake 9.4 %, daily Salt intake (> or = 5 gram)
      34.2%, daily saturated fat intake ( > or =10 % of daily energy intake) 47.0 % and
      physical inactivity 18.5 %. BMI was > or =25 Kg /m(2) in 18 percent and it was >
      or =30 Kg / m(2) in 3.2 percent population. Truncal obesity (WHR: men> 0.9; women
      > 0.8) was found 18.5 percent more in case of males (20.7). Abdominal obesity(men
      > or =102; women > or = 88)was found 15.7 percent more in case of males
      (20.6).18.5 percent population was found suffering from systolic hypertension> or
      =140 mm Hg )and 15 percent from diastolic hypertension(> or =90 mm Hg). Awareness
      of CHD risk factors was present in 30.0 percent population. Differences in
      prevalence of riskfactor in male and female were found statistically significant
      in case of smoking, alcohol consumption and abdominal obesity. The present study
      shows that prevalence of CHD risk factors increases significantly in men and
      women having BMI equal or more than 25 Kg /m(2) so this cutoff, should be used to
      determine obesity in Indian population.

PMID- 17193755
TI  - Geomatics and public health.
AB  - Geomatics technology has tremendous potential to address public health issues
      particularly under the present circumstances of global climate change and climate
      or technology induced human migration, which result in an increase in the
      geographical extent and re-emergence of vector-borne diseases. The authors
      present an overview of the science of geomatics, describe the potential impacts
      of climate change on vector-borne diseases and review the applications of remote
      sensing for disease vector surveillance.

PMID- 17193756
TI  - An overview of the recent trends in HIV/AIDS in the United States.
AB  - This paper reviews the recent trends in the HIV/AIDS disease in the United States
      focusing on how the disease has matured over time and has now started to affect
      population segments that were not typically considered at-risk. The data reveals
      that HIV/AIDS levels have increased among women while it has decreased among men.
      HIV/AIDS has disproportionately affected the African American population while
      the levels have declined among whites. The case fatality rates of AIDS have
      declined from about 93% to 6% between 1981 and 1995. Overall the epidemic has
      slowed in the United States and more people affected with this disease are living
      longer. This can be attributed to effective treatment available and the increase
      in the general awareness of the disease in the US.

PMID- 17193757
TI  - A microbiological study of bottled mineral water marketed in Ludhiana.
AB  - The microbiological quality of bottled mineral water marketed in Ludhiana was
      examined, Twenty three brands were analyzed for presumptive coliform count by
      multiple tube tests, and E. coli count was confirmed by Eijkman test. Bacterial
      and fungal loads were tested by membrane filtration test. Out of 23 only one
      sample (4.4%) showed the presumptive coliform count to be 460 most probable
      number (MPN)l 1 00ml,and 1 was found to be positive when tested by Eijkman test
      for Ecoli. In the membrane filtration test three samples (13%) showed more than
      two types of bacteria. Different types of bacteria isolated included Bacillus sp
      (19/23). Pseudomonas spp (13123), Ecoli, Klebsiella sp and S.albus one each Fungi
      was isolated from five of twenty three. (22%) samples. Only one brand of mineral
      water was unfit for human consumption. The rest of the samples were contaminated
      with non pathogenic flora.

PMID- 17193758
TI  - Assessment of nutritional status of pre-schoolers in slum areas of Udaipur City.
AB  - The present study was conducted in pre-schoolers (2-6 years) from ten different
      slums of Udaipur City in Rajasthan with the aim to their nutritional status. From
      the data collected and observations recorded was observed that majority of the
      subjects were from nuclear family with monthly family income of less than
      Rs.1500/-. Developmental pattern of these subjects indicated that the height with
      age of bothe male and female subjects increased, however, their body weight did
      not increase. More than 50% of these pre-schoolers showed symptoms of protein
      energy malnutrition and anaemia, while 22% had pigeon chest deformity due to
      vitamin D and calcium deficiency. Classification for degree of malnutrition as
      per IAP showed that majority of these subjects (66%) were under weight (Grade I
      and II). Waterlow's classification revealed that majority of these pre-schoolers
      were wasted (30%) or wasted and Stunted (42%). This malnutrition was either of
      PCM (past chronic) or CLM (current long duration) type as per Seoane and Latham's
      classification.

PMID- 17193759
TI  - Record based study of snake bite cases admitted at Shri Vasantrao Naik Government
      Medical College & Hospital, Yavatmal (Maharashtra).
AB  - The present hospital record based cross-sectional study was undertaken with the
      objectives of finding out the epidemiological profile of snake bite cases
      admitted in Shri V. N. Govt. Medical College and hospital during the period of
      1998-2002. The data was collected from the filled case papers of snake bite
      cases, through medical record section under the department of PSM and analyzed
      manually. The outcome of snake bite treatment was noted and defined. Proportional
      case rate of snake bite cases varied from 6.8 per 1000 admissions in 1998 to 6.0
      per 1000 in 2002. Snake bite cases were seen among Males (69.4%), 97.4% of cases
      were agricultural workers and labourers. The cases seen during the period of June
      to Aug (35.5%) followed by Septeber to November (33.5%). About 78.7% of the
      victims either got relived or cured with a experienced mortality 4.3%.

PMID- 17193760
TI  - Development and validation of risk scoring system for prediction of cancer
      cervix.
AB  - A Hospital based group matched case-control study was conducted to devise a risk
      scoring system for the prediction of cancer cervix at the Gynecology Clinic,
      Government Medical College Hospital, Nagpur, India. The study consisted of 230
      cases of cancer cervix (histopathologically confirmed) and equal number of
      controls, group matched for age. The risk factors considered were Illiteracy,
      long duration of married life (>25 years), Early Menarche (<13 years), marital
      status (widow, separated, divorcee), multiparity (> 3), h/o abortion, h/o tobacco
      use, h/o passive smoking, poor genital hygiene, (grade III & IV) and low
      socioeconomic status. Statistical Analysis included unconditional multiple
      logistic regression analysis Receiver Operating Characteristic (ROC) curve
      analysis. The overall predictive accuracy was calculated by Wilcoxon statistic as
      an equivalent of area under ROC curve. Five risk factors, illiteracy, poor
      genital hygiene, long duration of married life, multiparity and early menarche
      were identified to be significantly associated with cancer cervix. These factors
      were given statistical weights of 13, 10, 7, 5 and 5 respectively. A total score
      of 21 was found to be the best cut off for prediction and the overall predictive
      accuracy of the risk scoring system was calculated to be 0.74(0.67 - 0.81). In
      case of consistent further validation using other data sets this additive risk
      scoring system can be used for reducing the cost of universal screening by
      subjecting only high-risk subjects to laboratory screening procedure (Pap smear)
      in population setting.

PMID- 17193762
TI  - Study of unment need for family planning among married women of reproductive age
      in urban health central field practice area of Govt. Medical College, Aurangabad.
AB  - A community based cross sectional study was carried out in married reproductive
      age group women in Urban Health Centre field practice area of Govt. Medical
      College, Aurangabad. The study aimed to find out extent and socio-demographic
      correlates of unmet need for family planning. 20.54% of married women in
      reproductive age had unmet need for contraception, 3.61% for spacing births and
      16.93% for limiting births. The main reasons for unmet needwere, littie perceived
      risk of pregnancy due to perimenopausal age (32.471/o) lactation (31.16%),
      ignorance (12.32%) etc.

PMID- 17193761
TI  - Prevalence of anti HCV, HBsAg and HIV antibodies in high risk recipients of blood
      and blood products.
AB  - Along with hepatitis B virus (HBV) and human immunodeficiency virus (HIV),
      Hepatitis C virus (HCV) is emerging as a major transfusion hazard. 22 cases of
      haemophilia (A 19, B 3) and 20 cases of thalassaemia (2 16, E(2) 4) constituted
      the study group. Patients tested for anti HCV (using third generation ELISA),
      HBsAg and antibodies to HIV I and II. Prevalence of anti HCV was 54.5% in
      haemophilics and 5% in thalassaemics. HBsAg was detected in 9.09% haemophilics
      and 5% thalassaemics. No anti HIV was detected in this cohort. Anti HCV
      seropositivity in haemophilics has increased compare to previous studies.

PMID- 17193763
TI  - Peak expiratory flow rate of children working in lock factories.
AB  - Peak expiratory flow rate (PEFR) of 106 children working in different units of
      lock factory was measured and compared with age and sex matched control group of
      same socio-economic status children. All the children worked for about ten hours
      per day. It was observed that there was a significant decrease in PEFR of
      children working in the different units of lock factories i.e. Hand press,
      Polishing, Lock fitting, Lock packing units as compared to control group
      (P>0.001). The reduction percentage of PEFR was maximum in children working in
      polishing unit (25.48%).

PMID- 17193764
TI  - A study on utilization and quality of coverage of antenatal care services at the
      subcentre level.
AB  - A community based cross-sectional study was done by interviewing a sample of 360
      women of Anchuri Block in the district of Bankura, West Bengal to know the
      determinants of utilization and coverage quality of antenatal care services of
      subcentres using an appropriate scoring system for analysis. The study revealed
      underutilization of subcentres by the women and also sub-optimal performance of
      subcentres with regard to coverage quality of ANC services The main reason for
      under utilization of subcentres was found to be better service provision and easy
      accessibility of B.S. Medical College Hospital. Multiparous mothers were seen to
      be at a disadvantage both in terms of utilization of the source of choice as well
      as in terms of coverage of ANC services by subcentre ANMs.

PMID- 17193765
TI  - Awareness and training need of biomedical waste management among undergraduate
      students, Andhra Pradesh.
AB  - Total 463 undergraduate students (216 males & 247 females) of ASRAM medical
      college of Andlira Pradesh were surveyed regarding awareness about biomedical
      waste management. Most of the students have heard about biomedical waste. Some of
      them were aware that it causes health hazards. But knowledge about category of
      wastes, duration of waste storage, responsibility of waste, type of bags used for
      collection, identification of Biohazard symbol was poor. Awareness of Biomedical
      waste. management and Handling rule 1998 was also poor. There were gaps in
      various aspects of Biomedical waste management among medical students.
      Appropriate training or inclusion of a topic in undergraduate medical curriculum
      can fulfill this.

PMID- 17193766
TI  - A study on the effectiveness of DOTS on tuberculosis patients treated under
      RNTCP.
AB  - A total of 88 Tuberculosis patients who registered for treatment were followed up
      until their completion. These patients were given treatment under the Government
      of India implemented RNTCP in the year 1999-2000 in a Tuberculosis unit in
      Bangalore Mahanagara Palike. Majority of the patients were male and from lower
      middle class In the present study the cure rate was 72.00 %, treatment completion
      was 80.55%, default patients were 22.72% and chronic cases were 6.25%.

PMID- 17193767
TI  - Evaluation of arm and thigh circumference in screening low birth weight newborns.
AB  - The present cross-sectional study collected data regarding birth weight along
      with arm and thigh circumference of 174 consecutive newborns delivered at
      Maternity Hospital, Tasgaon during 2003. To compare & evaluate utility of arm &
      thigh circumferences for the detection of LBW newborns. Assessment of the best
      suitable measurement for identification of low birth weight newborns was made by
      comparison of Coefficient of Determinants (R(2)), Sensitivity and Specificity
      values and Kappa Statistics. The estimated cut off points of arm and thigh
      circumference for given value of birth weight 2.5 kg. were 9.1 cm and 14.2 cm.
      respectively. Although both measurements are highly sensitive, present study
      established supiriority of arm circumference over thigh circumference in
      predicting low birth weight newborns. Thigh circumference is more reliable.
      Advantages of these measurements are their simplicity & low cost.

PMID- 17193769
TI  - Struggle over controlled drug prescribing rights.

PMID- 17193768
TI  - Obstetric history and reproductive tract infections among married female (15-44
      yrs.) in rural area of district Meerut, U.P.
AB  - The prevalence of RTIs in 600 married females (15-44 yrs.) representing 12
      subcentre villages of Daurala block of Meerut was 35.3%. The reproductive tract
      infections were significantly associated with place of last delivery (P< 0.001),
      person conducted the last delivery (P< 0.001) and in women had history of
      abortions (P< .005).

PMID- 17193770
TI  - "It is hard to see how criminalisation helps to prevent new HIV infections".

PMID- 17193771
TI  - Meet your new nurse leaders.

PMID- 17193772
TI  - Why is bullying still rife?

PMID- 17193773
TI  - Urinary incontinence in women.
AB  - NICE guidance has been issued to help health professionals diagnose and manage
      urinary incontinence in women. The problem is common but under-reported as women
      are often too embarrassed to seek help. This report outlines assessment,
      diagnosis and treatment options for women with stress, urge or mixed urinary
      incontinence and overactive bladder syndrome.

PMID- 17193774
TI  - Muscle physiology. Part 2: Skeletal muscles and muscle fibres.

PMID- 17193775
TI  - A practical guide to carrying out skin-prick allergy testing.
AB  - Skin-prick testing is one of the cheapest and most widely available methods for
      diagnosing allergies. With ever-increasing numbers of nurses performing the tests
      in nurse-led clinics, it is essential that the procedure is fully understood and
      carried out correctly, particularly in terms of patient safety. This article
      discusses the indications, contraindications, advantages and disadvantages of
      skin-prick testing and details how to carry out the procedure.

PMID- 17193776
TI  - Using specialist nurse mentors to boost placement capacity.
AB  - Mentors play a pivotal role in assessing and supporting nursing students. This
      can be rewarding but stressful. With increasing numbers of students requiring
      clinical placements, ward mentors are becoming overloaded. This article examines
      a new method of supporting senior nursing students in placement while alleviating
      the pressures on overworked mentors. It recommends the use of specialist nurses
      to support pre-registration students through a structured learning pathway. The
      scheme also opens up new areas for clinical allocations. This is a summary: the
      full paper can be accessed at nursingtimes.net.

PMID- 17193777
TI  - A comparison of UK and US mortality outcomes.
AB  - In response to US colleagues' concerns about the NHS, we undertook a comparison
      of mortality rates in England and Wales and the US. Figures for 1974-2000 were
      obtained from World Health Organization data on all-cause and cancer mortality
      rates. Overall rates fell in all three countries but there was a more significant
      drop in England and Wales over the period. This is a summary: the full paper can
      be accessed at nursingtimes.net.

PMID- 17193778
TI  - The aftermath of a heat wave: a research challenge.

PMID- 17193779
TI  - Electromagnetic fields, science and public concern.

PMID- 17193780
TI  - Temperature related mortality and ambulance service interventions during the heat
      waves of 2003 in Ticino (Switzerland).
AB  - OBJECTIVES: This study investigates a potential increase in mortality and in the
      demand for ambulance emergency services among the elderly in particular, in
      Ticino in the summer of 2003. METHODS: Mortality rates and emergency ambulance
      interventions rates were compared with records from the previous years. We
      considered the whole population, aged 65 and over, as well as 75 and over.
      RESULTS: The 2003 mortality in the population was not significantly different
      from the previous years. The number of deaths among the elderly showed a small
      but significant deviation from the expected values during the first heat wave in
      June 2003, with no significant impact on the seasonal results. The number of
      ambulance service interventions was larger than during the previous years.
      CONCLUSION: These results are consistent with findings in other studies. The heat
      waves (especially in June), were correlated with a higher number of ambulance
      callouts. In addition to some geographic, climatic, and social factors that had a
      protective impact, the response of the emergency services is likely to have
      contributed to a certain reduction in mortality.

PMID- 17193781
TI  - Syndromic surveillance use to detect the early effects of heat-waves: an analysis
      of NHS direct data in England.
AB  - OBJECTIVES: To investigate the effects of high ambient temperatures, including
      the summer 2003 heat-episode, on NHS Direct usage and its suitability as a
      surveillance tool in heat health warning systems. METHODS: Analyses of data on
      calls to NHS Direct in English Regions in the period Dec 2001-May 2004. Outcomes
      were daily rates of all symptomatic calls, and daily proportion of calls for
      selected causes (fever, vomiting, difficulty breathing, heat/sun-stroke) RESULTS:
      Total calls were moderately increased as environmental temperature increased;
      this effect was greatest in calls for young children and for fever. Total calls
      were moderately elevated during two summer heat episodes in 2003: calls
      specifically for heat/sun stroke increased acutely in response to these episodes.
      No association was apparent between environmental temperature and proportion of
      calls for vomiting and difficulty breathing. CONCLUSIONS: Calls to NHS Direct are
      sensitive to daily temperatures and extreme weather. NHS Direct is timely and has
      great potential in health surveillance. Calls for heat- and sun-stroke are now
      routinely monitored as part of the UK Heat-wave plan

PMID- 17193782
TI  - The prevalence of symptoms attributed to electromagnetic field exposure: a cross
      sectional representative survey in Switzerland.
AB  - OBJECTIVES: To investigate health risk perception as well as to assess the
      prevalence of self-reported symptoms attributed to electromagnetic fields (EMF)
      and other environmental exposures in the general population of Switzerland.
      METHODS: Between May and June 2004, telephone interviews of a representative
      sample of the Swiss population (n=2048, >14 years old) about: (1) health symptoms
      attributed to five environmental factors (one of which was EMF), (2) health risk
      perception related to 12 environmental risk factors (five of which were different
      EMF sources). RESULTS: We found a prevalence of 5% (95% CI 4-6%) for
      electromagnetic hypersensitivity (EHS) in our study sample. The most common
      health complaints among EHS individuals were sleep disorders (43%) and headaches
      (34%), which were mostly attributed to power lines and mobile phone handsets. In
      addition, 53 percent (95% CI 51-55%) were worried about adverse health effects
      from EMF, without attributing their own health symptoms to them. CONCLUSIONS: The
      large proportion of the population who is concerned or attributes own symptoms to
      EMF may cause societal conflicts given the ubiquity of EMF in our everyday life.

PMID- 17193783
TI  - Magnetic field exposure and neurodegenerative diseases--recent epidemiological
      studies.
AB  - OBJECTIVES: To analyse the results of recent studies not yet included in a 2003
      report of the International Commission on Non-Ionizing Radiation Protection
      (ICNIRP) on occupational exposure to low-frequency electromagnetic fields as
      potential risk factor for neurodegenerative diseases. METHODS: A literature
      search was conducted in the online databases of PubMed, ISI Web of Knowledge,
      DIMDI and COCHRANE, as well as in specialised databases and journals. Eight
      studies published between January 2000 and July 2005 were included in the review.
      RESULTS: The findings of these studies contribute to the evidence of an
      association between occupational magnetic field exposure and the risk of
      dementia. Regarding amyotrophic lateral sclerosis, the recent results confirm
      earlier observations of an association with electric and electronic work and
      welding. Its relationship with magnetic field exposure remains unsolved. There
      are only few findings pointing towards an association between magnetic field
      exposure and Parkinson's disease. CONCLUSIONS: The epidemiological evidence for
      an association between occupational exposure to low-frequency electromagnetic
      fields and the risk of dementia has increased during the last five years. The
      impact of potential confounders should be evaluated in further studies.

PMID- 17193784
TI  - Social differences in the burden of long-standing illness in Denmark.
AB  - OBJECTIVES: To estimate the impact of diseases on social differences in life
      expectancy and expected lifetime with illness among Danes in 1995-99. METHODS:
      Expected lifetime with and without long-standing illness were calculated for
      groups with low, medium and high educational levels. Estimates based on observed
      rates of mortality and prevalence of illness were compared with those based on
      rates from which a specific disease had been eliminated. RESULTS: Partial life
      expectancy (age 30-75) would increase by almost 1.5 years if cancer were
      eliminated. Expected lifetime without long-standing illness would increase by
      approximately 1 year. Elimination of cardiovascular diseases would increase
      partial life expectancy, mainly among men with a low educational level. If
      diseases of the musculoskeletal system were eliminated the benefit would be
      greatest for persons with a low educational level. CONCLUSIONS: The gain in life
      expectancy to be expected by eliminating certain diseases decreased with
      educational level. Elimination of cancer would extend lifetime both with and
      without illness for all educational levels.

PMID- 17193785
TI  - Social dimensions of mortality from external causes in Lithuania: do education
      and place of residence matter?
AB  - OBJECTIVES: To assess inequalities in mortality from external causes by the level
      of education and the place of residence during the period of socio-economic
      transition in Lithuania. METHODS: Information on deaths, place of residence, and
      the level of education of persons aged 25 and older was derived from the National
      Database of Lithuania and censuses for 1989 (n=3537) and 2001 (n=4790). RESULTS:
      Mortality from external causes of Lithuanian urban and rural populations was
      strongly associated with the level of education. Educational inequalities
      increased throughout the period of socio-economic transition. In urban areas,
      mortality among the least educated population was 3.20 times higher in 1989 and
      3.37 times higher in 2001, compared to those with university-level education. In
      rural areas the educational mortality rate ratios reached 3.47 and 4.33,
      respectively. The greatest educational inequalities were observed in suicide
      mortality, especially among males. CONCLUSIONS: The results of this study
      disclosed increasing inequalities in mortality from external causes. Less
      educated populations, especially in rural areas, should receive particular
      attention in the development of strategies for the prevention of mortality from
      external causes.

PMID- 17193786
TI  - Regarding technique in October article.

PMID- 17193787
TI  - Recruit, reward, and retain: how to build hygiene loyalty to you and your
      practice.

PMID- 17193788
TI  - Articulators: should we accept the status quo? A doctor-technician liaison's
      perspective.

PMID- 17193789
TI  - Implant treatment planning for the medically compromised patient: a case report
      of full-mouth reconstruction with dental implants.

PMID- 17193790
TI  - Progressive taper technology: rationale and clinical technique for the new
      ProTaper universal system.
AB  - ProTaper Universal has produced a comprehensive yet simple solution for dentists
      in search of a single, versatile system that solves major endodontic problems
      from access to obturation. The key in high-performance endodontics is to produce
      the most and the best while doing the least. We know this as leverage.
      Breakthrough safety and simplicity features, combined with optimum efficiency,
      are at the heart of ProTaper Universal. The net intentional result of these
      newest endodontic technologies is that the practitioner can predictably and
      consistently produce exceptional patient outcomes (Figures 15 to 20).

PMID- 17193791
TI  - Closing the gap with minimal preparation veneers.

PMID- 17193793
TI  - Ten commonly asked computer questions ... and answers. Part 1.
AB  - I hope that you have learned something from this article that will help you get
      through your next computer crisis. Remember that most computer problems are not
      your fault and they are not the end of the world. It stinks when your car breaks
      down, and it stinks when your PC crashes, but you will get through it. If your PC
      does crash, write down what you were doing when it crashed, any changes that were
      made, any software that was installed, and take a deep breath. You will be able
      to help get the problem solved quicker if you stay relaxed. Part 2 of this
      article, to be published in a future issue of Dentistry Today, will answer the
      next 5 commonly asked computer questions.

PMID- 17193792
TI  - The direct Class IV restoration: case report.

PMID- 17193794
TI  - Presenting occlusion disease in 3-D for greater case acceptance.

PMID- 17193795
TI  - Erasing buffalo mentality: a new leadership paradigm for dentists.

PMID- 17193796
TI  - Dental office lighting.

PMID- 17193797
TI  - Restoring the partial edentulous patient in the aesthetic zone using implants and
      all-ceramic restorations: case report.

PMID- 17193798
TI  - Managing stress with composite resin, Part 1: The restorative-tooth interface.

PMID- 17193799
TI  - Climate change and health.

PMID- 17193800
TI  - Statutory disclosure in article 280 of the Turkish Penal Code.
AB  - A new Turkish Penal Code came into effect on 1 June 2005. Article 280 concerns
      health care workers' failure to report a crime. This article removes the
      responsibility from health care workers to maintain confidentiality, but also
      removes patients' right to confidentiality. It provides for up to one year of
      imprisonment for a health care worker who, while on duty, finds an indication
      that a crime might have been committed by a patient and who does not inform the
      responsible authorities about it. This forces the health care worker to divulge
      the patient's confidential information. A patient who thinks he or she may be
      accused of a crime may therefore not seek medical help, which is the universal
      right of every person. The article is therefore contrary to medical ethics, oaths
      taken by physicians and nurses, and the understanding of patient confidentiality.

PMID- 17193801
TI  - Ethical conflicts in prehospital emergency care.
AB  - This article analyses and presents a survey of ethical conflicts in prehospital
      emergency care. The results are based on six focus group interviews with 29
      registered nurses and paramedics working in prehospital emergency care at three
      different locations: a small town, a part of a major city and a sparsely
      populated area. Ethical conflict was found to arise in 10 different nodes of
      conflict: the patient/carer relationship, the patient's self-determination, the
      patient's best interest, the carer's professional ideals, the carer's
      professional role and self-identity, significant others and bystanders, other
      care professionals, organizational structure and resource management, societal
      ideals, and other professionals. It is often argued that prehospital care is
      unique in comparison with other forms of care. However, in this article we do not
      find support for the idea that ethical conflicts occurring in prehospital care
      are unique, even if some may be more common in this context.

PMID- 17193802
TI  - Competent patients' refusal of nursing care.
AB  - Competent patients' refusals of nursing care do not yet have the legal or ethical
      standing of refusals of life-sustaining medical therapies such as mechanical
      ventilation or blood products. The case of a woman who refused turning and
      incontinence management owing to pain prompted us to examine these situations. We
      noted several special features: lack of paradigm cases, social taboo around
      unmanaged incontinence, the distinction between ordinary versus extraordinary
      care, and the moral distress experienced by nurses. We examined this case on the
      merits and limitations of five well-known ethical positions: pure autonomy,
      conscientious objection, paternalism, communitarianism, and feminism. We found
      each lacking and argue for a 'negotiated reliance' response where nurses and
      others tread as lightly as possible on the patient's autonomy while negotiating a
      compromise, but are obligated to match the patient's sacrifice by extending
      themselves beyond their usual professional practice.

PMID- 17193803
TI  - The dialectic tension between 'being' and 'not being' a good nurse.
AB  - The aim of this hermeneutic study was to gain a broader understanding of nurses'
      workload and what characterizes a nurse's experience in terms of the various
      levels of intensity of nursing care. Twenty-nine nurses participated in seven
      focus groups. The interpretation process took place in six different phases and
      the three laws of dialectics were used as interpretation rules. An optimal
      nursing care intensity level can be understood as a situation characterized by
      the balance between the intensity of care needed by patients and the external and
      internal factors of the current nursing care situation. The nurses' work
      situation can be understood as a dialectic struggle between 'being' and 'not
      being' a good nurse; this can be said to be the underlying root metaphor. Nursing
      care can be understood as consisting of 'complex and meaningful caring
      situations'. Dialectics can be used as a fruitful method of revealing the
      complexity of clinical reality.

PMID- 17193804
TI  - Development and initial validation of the Stress of Conscience Questionnaire.
AB  - Stress in health care is affected by moral factors. When people are prevented
      from doing 'good' they may feel that they have not done what they ought to or
      that they have erred, thus giving rise to a troubled conscience. Empirical
      studies show that health care personnel sometimes refer to conscience when
      talking about being in ethically difficult everyday care situations. This study
      aimed to construct and validate the Stress of Conscience Questionnaire (SCQ), a
      nine-item instrument for assessing stressful situations and the degree to which
      they trouble the conscience. The items were based on situations previously
      documented as causing negative stress for health care workers. Content and face
      validity were established by expert panels and pilot studies that selected
      relevant items and modified or excluded ambiguous ones. A convenience sample of
      444 health care personnel indicated that the SCQ had acceptable validity and
      internal consistency (Cronbach's alpha exceeded 0.83 for the overall scale).
      Explorative factor analysis identified and labelled two factors: 'internal
      demands' and 'external demands and restrictions'. The findings suggest that the
      SCQ is a concise and practical instrument for use in various health care
      contexts.

PMID- 17193805
TI  - Inclusion practice in lung cancer trials.
AB  - This article presents the results of a qualitative study on the ethical aspects
      of inclusion practice for radiotherapy patients taking part in clinical research.
      The study focused on the standards and values of this process. Patients and
      physicians were interviewed about their views and experiences. Analysis of these
      interviews showed that candidate research participants need better protection
      from unwanted factors that could influence their choice about participation.
      Researchers need proper education about regulation, codes and directives in the
      field of research ethics, and they should be aware of the underlying ethical
      concepts of these regulations. A sound institutional ethics policy is necessary
      in order to guide medical staff in decisions about the inclusion of patients in
      trials.

PMID- 17193806
TI  - [The Revista Espanol de Salud Publica: an octogenarian with a very good health].

PMID- 17193807
TI  - [The Revista de Sanidad e Higiene Publica].

PMID- 17193808
TI  - [The beginnings of public health studies in Renaissance Spain].
AB  - A very brief synthesis is provided of the findings of the historical research the
      author first began more than forty years ago as to the initial beginnings of the
      studies on public health in Renaissance Spain. The role played by royal power
      from the standpoint of the beginnings of the modern State, the influence of
      Hippocratic environmentalism, keeping up cleanliness-related privileges at the
      personal level, the first beginnings of hygiene on a widespread basis in related
      to the plague epidemics and the contributions to medical care conditioned by the
      change in poverty-related values are discussed in turn.

PMID- 17193809
TI  - [Professional ethics and institutional ethics: convergence or conflict?].
AB  - During the last decades, an important debate about professions in general, and
      particularly about the medical profession, has taken place. The classic idea that
      professionals do have a "special mora lity", different from the common morality,
      which among other things give them legal impunity, came to a head. This causes a
      great deal of confusion among the professionals, incapable of reacting and
      redefining precisely their own identity. Some new concepts, like that of
      "internal morality" of professional activities, made the debate more difficult
      and confusing. On the other hand, the everyday more powerful influence of free
      market forces in the health care economy, has made that some decisions taken by
      health care managers would be considered by physicians as opposed to their
      professional duties and incompatible with them. This has been the origin of a
      debate about what is called in North America "New Professionalism". This debate
      deals with basic questions about the health care professional's identity at the
      beginning of this new Century.

PMID- 17193810
TI  - [The role of epidemiology in the future of public health].
AB  - The evolution of epidemiology from a risk factor centred approach to a population
      epidemiology, focused in etiologic theories and more connected with the social
      and environmental context could support but not guarantee the implementation of
      public policies oriented to improve population health. In this article, we
      comment on several factors that, from the research, professional and health
      services viewpoints, could determine a better linkage between epidemiology and
      public health policies. Creativity and innovation, hybridization, a compromise
      with the fundamental values of public health and a prominent role in health
      services are some of the main factors.

PMID- 17193811
TI  - [Public health and public health systems sustainability].
AB  - Public health and healthcare originally started out separately from one another
      in the past, having later further developed taking different paths in modern
      times. The major development the health systems underwent in the last half of the
      20th century entailed a heightening of the individual standpoint and a division
      of these two approaches despite the attempts made to bring them together as of
      the WHO Alma-Ata Conference in 1978. The waning of rationalism and other social
      phenomena had a hand the collective or population-oriented focus being focused on
      to a lesser degree in Public Health, but these trends also gave rise to a growing
      problem of rationality in individual healthcare and sustainability in the public
      health systems. The debate on the current scene stands to set out the
      sustainability-related problems mediated by internal and external agents and to
      revise Public Health's possible contribution to the improvement thereof by
      advocating yet a further attempt at bringing together and integrating these two
      diverging standpoints.

PMID- 17193812
TI  - [Contributions of systematic review and meta-analysis to public health].
AB  - Meta-analysis has several precedents; even in Confucius (VI BC) one can find a
      sentence about the synthesis of knowledge. Meta-analysis is a consequence of the
      paradigm of induction. Within this paradigm of research, meta-analysis gives an
      analysis of the principle of consistency of a causal association (2nd principle
      of Hill). It has promoted the development of evaluation questionnaires and
      protocols for different designs, mainly clinical trials. It favoured the movement
      of evidence-based medicine, which is behind the creation of agencies for the
      evaluation of health technologies, and the recognition of public health
      professionals dedicated to research methods (mainly epidemiologists). The
      contributions of meta-analysis to public health are not distinguishable from
      others made to other specialties, although in the field of research methods it
      has contributed to the study of publication bias and to the search of
      determinants of heterogeneity, the lack of consistency among the individual
      studies.

PMID- 17193813
TI  - [The impact of economics on health policy and management in Spain].
AB  - BACKGROUND: Despite the intrinsic value of scientific disciplines, such as
      Economics, it is appropriate to gauge the impact of its applications on social
      welfare, or at least--Health Economics' (HE) case--its influence on health policy
      and management. METHODS: The three relevant features of knowledge (production,
      diffusion and application) are analyzed, more from an 'emic' perspective--the one
      used in Anthropology relying on the experience of the members of a culture--than
      from an 'etic' approach seated on material descriptions and dubious statistics.
      RESULTS: The soundness of the principles and results of HE depends on its
      disciplinary foundations, whereas its relevance--than does not imply translation
      into practice--is more linked with the problems studied. Important contributions
      from Economics to the health sphere are recorded. HE in Spain ranks seventh in
      the world despite the relatively minor HE contents of its clinical and health
      services research journals. HE has in Spain more presence than influence, having
      failed to impregnate sufficiently the daily events. CONCLUSIONS: HE knowledge
      required by a politician, a health manager or a clinician is rather limited; the
      main impact of HE could be to develop their intuition and awareness.

PMID- 17193814
TI  - [More than thirty years of illicit drugs in Spain: a bitter story with some
      messages for the future].
AB  - The phenomenon of illicit drug use in Spain during the last thirty years has been
      marked by the extremely serious consequences of heroin use (mainly injecting).
      More than 300,000 persons were treated for heroin dependence, 20,000-25,000 died
      from overdose, 100,000 became infected with HIV through drug injection and quite
      more with hepatitis virus. Some of these consequences can be attributed to the
      delay in the implementation of effective interventions, such as methadone
      maintenance treatment (MMT). Currently, the decreasing number of injectors and
      the positive effects of interventions, mainly MMT, have led to an important
      decline of the mentioned health problems. However, overdose mortality remains
      very high (more than 700 deceased per year), prevalence of both HIV and HCV are
      still high among injectors, and consequences of chronic liver diseases are
      emerging. In the last years the use of cocaine and associated problems have
      increased a lot. Nowadays there are more than 100,000 weekly cocaine users,
      25.000 persons are annually treated from cocaine abuse or dependence, and cocaine
      has an important impact on medical emergency services, while its impact on
      mortality is unknown. Both cannabis use and related problems are increasing too
      (there are half a million of daily users). We propose to maintain and to
      strengthen harm reduction programs (MMT, syringe exchange, save-use and injection
      rooms, hepatitis A and B vaccination, etc.), to urgently develop specific
      strategies targeted to reduce overdose mortality and cocaine related problems,
      and to re-evaluate the effectiveness of preventive and supply control strategies.

PMID- 17193815
TI  - [Medline criteria for scientific journals selection. Methodology and indicators.
      Application to Spanish medical journals paying special attention to public
      health].
AB  - Due to the strict selection process applied to its indexed journals, Medline is
      the most prestigious database in the Health and medicine field. The aim of this
      paper is both to analyze its selection criteria and translate into indicators
      that can be applied to Spanish medical journals willing to enter the Index
      Medicus. Analysis samples and methodology to apply obtained from the five groups
      of criteria considered by Medline (namely, Scope and coverage, Quality of
      contents, Quality of editorial work, Production quality and Audience) are
      proposed. A list of qualitative and quantitative indicators related to the five
      groups of criteria used by Medline is presented; namely, journal scientific
      output in the national and international context of the discipline, citation,
      analysis of the editorial committees, the editorial process and the peer-review
      system, indicators on compliance with the Vancouver guidelines, journal layout
      and informational quality, attractiveness, audience, journal visibility and
      interest as regards Medline goals.

PMID- 17193816
TI  - [Occupational injury, a public health priority].
AB  - The aim of this review is to stimulate new ideas and actions for the prevention
      of this important public health problem. In 2002 and 2003, respectively, the
      number of non-fatal occupational injuries was 971,406 and 906,638. Thus, every
      day in Spain there are more than 2500 non-fatal and between 2 and 3 fatal
      occupational injuries. Although the profile of the at-risk worker population has
      changed greatly over the past decade, both quantitatively and qualitatively, the
      risk of occupational injury still centers on blue collar workers, whether
      qualified or nonqualified, in the primary and secondary sectors of economic
      activity. The most common mechanisms of occupational injuries are overexertion
      for non-fatal injuries and traffic-related for fatal events. The adverse health
      consequences of new types of employment, which emphasize flexibility and
      deregulation of the labour market, are exemplified by the association between
      temporary employment and increased risk of occupational injury. New injury
      prevention programs have emerged in the last decade, but they appear to have had
      limited impact. Preventive activities should focus both on working conditions at
      the company level (micro) as well as on employment and industrial public policies
      (macro). Greater evaluation is needed of these latter policies.

PMID- 17193818
TI  - [The "Instituto de Salud Carlos III" and the public health in Spain. Origin of
      laboratory medicine and of the central laboratories and research in public
      health].
AB  - The "Instituto de Salud Carlos III" is the Central Public Health Laboratory in
      Spain with an important component of scientific research in health related areas,
      such as cancer, cardiovascular diseases, infectious diseases and environmental
      health. The article describes the development of the Public Health Institutes.
      arising from the introduction and development of scientific and laboratory based
      medicine and the introduction of vaccination and sanitation with the control of
      water and food. At about the same time, the discoveries in microbiology and
      immunology were produced, being the research activities incardinated with the
      practical advances in the control of products. To cope with the practical needs,
      Institutions were created with the responsibility of providing smallpox vaccine
      but incorporating very soon production of sera and other vaccines and water and
      sanitation control and foods control. At the same time. colonization of countries
      specially in Africa, South East Asia and explorations in Central America confront
      the Europeans with new diseases and the need of laboratories where to study them.
      These circumstances gave rise to the birth of the Central Public Health
      Laboratories and the National institutes of Health at the beginning of the XX
      century in many countries. In Spain, the Spanish Civil War was a breaking point
      in the development of such an institution that finally was reinvented with the
      creation of the Instituto de Salud Carlos III, in 1986, incorporating research
      and epidemiological surveillance and control of diseases and also the
      responsibilities of the Food and Drug Control, lately separated from it.

PMID- 17193817
TI  - [Proposals for the reform of public health services in Catalonia].
AB  - In the year 2004 the government of Catalonia undertook a process to reform its
      public health services. In this context, it created a working groupinvolving
      experts from diverse backgrounds to analyse the reforms to be undertaken, the
      Scientific Committee for the Reform of Public Health in Catalonia. Its members
      produced eight documents on specific aspects of public health, from which a
      global report of the Committee was compiled by the end of 2005. This paper makes
      a synthesis of their production, and includes as an annex their recommendations
      and proposals. Public health policies should be structured around three main
      goal: the reduction of health inequalities, the control and removal of social and
      environmental risks, and effective improvements in quality of life. To reach
      them, common criteria are defined as main directions. These are based in
      favouring decentralization of public health services and their administration,
      linking public health activities with health care services, designing
      interventions with a population perspective, and reinforcing cross-sectional
      implications of public health. The work of this Committee is produced in the
      context of an international debate on the future of public health services and
      the disproportion between its contribution to health and well being and its
      resources and visibility. The Committee produced proposals and recommendations
      which can he grouped in five facets: consolidating a solid and coherent system,
      developing an organizational reform, defining a port-folio of services, adopting
      improvements in management, and taking into account cross sectional aspects
      relating to public health.

PMID- 17193819
TI  - Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal
      models.
AB  - Once a poorly understood pathologic entity, gastrointestinal stromal tumor (GIST)
      has emerged in recent years as a distinct oncologic-molecular paradigm that is
      now a leading model for kinase-targeted therapies in Oncology. Most GISTs are KIT
      expressing and KIT-signaling driven mesenchymal tumors, many of which have KIT
      activating mutations. A small subset of GIST show activating mutations in PDGFRA,
      encoding for a related member of the type III receptor tyrosine kinase family.
      The revelation of KIT expression as a diagnostic signature of GIST has not only
      revolutionized the pathologic criteria in classifying GIST, but also shed light
      onto the histogenesis of these tumors. The similarities in KIT immunoreactivity
      and ultrastructural appearance between GISTs and the intestinal pacemaker, the
      interstitial cells of Cajal (ICC), suggested that GISTs derive from or
      differentiate toward the ICC lineage. KIT plays a significant role in
      proliferation, survival, and differentiation of hematopoietic stem cells, mast
      cells, melanocytes, and interstitial cells of Cajal; and activating KIT mutations
      have been identified in tumors affecting most of these cell lineages. The
      observation that KIT mutations may be inherited, as seen in familial GIST
      syndrome, was used to develop murine models harboring a germline gain-of-function
      mutation, as a model for studying of KIT oncogenic mechanisms. These murine
      models of human GIST promise to become powerful preclinical tools in elucidating
      oncogenic signaling mechanisms by using genetic approaches and targeted
      pharmacological intervention. As true animal models of human cancer, they provide
      superior information compared with the more commonly used xenografts and
      transgenic mouse models. This review summarizes the recent knowledge on the
      central role of KIT oncogenic activation and subsequent signal transduction in
      the pathogenesis of GIST. In addition, we provide an updated discussion on
      familial GIST syndrome in relationship to genotype-phenotype characteristics. A
      succinct description of the available murine models of human GIST is presented
      and their applicability in further understanding of the KIT oncogenic signaling,
      drug screening, and mechanisms of drug resistance is discussed. This is a US
      government work. There are no restrictions on its use.

PMID- 17193820
TI  - Gastrointestinal stromal tumors: pathology and prognosis at different sites.
AB  - Gastrointestinal (GI) stromal tumors (GISTs) are the most common mesenchymal
      tumors specific to the GI tract, generally defined as KIT (CD117)-positive tumors
      with a characteristic set of histologic features. These tumors, derived from
      Cajal cells or their precursors, most commonly occur at the age >50 years in the
      stomach (60%), jejunum and ileum (30%), duodenum (4-5%), rectum (4%), colon and
      appendix (1-2%), and esophagus (<1%), and rarely as apparent primary
      extragastrointestinal tumors in the vicinity of stomach or intestines. Their
      overall incidence has been estimated as 10 to 20 per million, including
      incidental minimal tumors. GISTs are rare in children (<1%) and almost
      exclusively occur in stomach. They are common in patients with neurofibromatosis
      1, who have a predisposition to (multiple) small intestinal GISTs. GISTs contain
      a spectrum from minute indolent tumors to sarcomas at all sites of occurrence.
      Their gross patterns are diverse, including nodular, cystic, and diverticular
      tumors. External involvement of pancreas and liver can simulate primary tumor in
      these organs. In general, gastric tumors have a more favorable prognosis than the
      intestinal ones with similar parameters. Gastric GISTs < or =10 cm and < or =5
      mitoses per 50 HPFs have a low risk for metastasis, whereas those with >5 per 50
      HPFs and >5 cm in diameter have a high risk for metastasis. In contrast, all
      intestinal GISTs >5 cm independent of mitotic rate have at least moderate risk
      for metastases, and all >5 mitoses per 50 HPFs have a high risk for metastases.
      Intestinal GISTs < or =5 cm with < or =5 mitoses per 50 HPFs have a low risk for
      metastases. Gastric GISTs can be divided into histologic subgroups including 4
      spindle cell and 4 epithelioid variants. Intestinal GISTs are a histologically
      more homogeneous group and often contain distinctive extracellular collagen
      globules, skeinoid fibers. Immunohistochemical demonstration of KIT, CD34, or
      protein kinase theta positivity helps to properly identify these tumors.

PMID- 17193821
TI  - GIST under imatinib therapy.
AB  - The prognosis of patients with a GIST improved significantly since the
      introduction of imatinib mesylate treatment, leading to disease control in 70% to
      85% of patients. The response depends on the presence/ absence and type of
      mutations in the KIT or Platelet derived growth factor receptor. Unfortunately,
      we are increasingly faced with the problem of resistance to imatinib treatment,
      mainly secondary resistance, which by definition occurs after at least 6 months
      of initial response to the drug. The effects of imatinib on a GIST are still in
      full exploration and this review focuses upon the available data on the phenotype
      and genotype of a GIST treated with imatinib. Two settings are elaborated
      separately, a responding/stable GIST, and a resistant GIST. In addition, the
      attention will be drawn to remarkable (immuno)phenotypic changes that can occur
      in a GIST under imatinib treatment.

PMID- 17193822
TI  - KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs).
AB  - Mutually exclusive KIT and PDGFRA mutations are central events in GIST
      pathogenesis, and their understanding is becoming increasingly important, because
      specific treatment targeting oncogenic KIT and PDGFRA activation (especially
      imatinib mesylate) has become available. KIT mutations in GIST are clustered in
      four exons. Most common are exon 11 (juxtamembrane domain) mutations that include
      deletions, point mutations (affecting a few codons), and duplications (mostly in
      the 3' region). The latter mutations most often occur in gastric GISTs. Among
      gastric GISTs, tumors with deletions are more aggressive than those with point
      mutations; this does not seem to hold true in small intestinal GISTs. Exon 9
      mutations (5-10%) usually are 2-codon 502-503 duplications, and these occur
      predominantly in intestinal versus gastric GISTs. Lesser imatinib sensitivity of
      these tumors has been noted. Kinase domain mutations are very rare; GISTs with
      such mutations are variably sensitive to imatinib. PDGFRA mutations usually occur
      in gastric GISTs, especially in the epithelioid variants; their overall frequency
      is approximately 30% to 40% of KIT mutation negative GISTs. Most common is exon
      18 mutation leading Asp842Val at the protein level. This mutation causes imatinib
      resistance. Exon 12 and 14 mutations are rare. Most mutations are somatic (in
      tumor tissue only), but patients with familial GIST syndrome have consitutitonal
      KIT/PDGFRA mutations; >10 families have been reported worldwide with mutations
      generally similar to those in sporadic GISTs. GISTs in neurofibromatosis 1
      patients, children, and Carney triad seem to lack GIST-specific KIT and PDGFRA
      mutations and may have a different disease mechanism. Secondary mutations usually
      occur in KIT kinase domains in patients after imatinib treatment resulting in
      resistance to this drug. Mutation genotyping is a tool in GIST diagnosis and in
      assessment of sensitivity to kinase inhibitors. This is a US government work.
      There are no restrictions on its use.

PMID- 17193823
TI  - GIST: particular aspects related to cell cultures, xenografts, and cytogenetics.
AB  - In less than half a decade, gastrointestinal stromal tumors (GIST) have emerged
      from historical anonymity to become a model of kinase-targeted therapies.
      Approximately 80% to 85% of GISTs harbor activating mutations of the KIT or
      PDGFRA tyrosine kinase genes, and such mutations have predictive and prognostic
      value. In this regard, the in vitro and in vivo models have provided valuable
      tools for understanding the molecular pathology of this interesting neoplasm.
      This review charts particular aspects in the field of cell cultures and tumor
      xenografts in nude mice in GIST and their implication in the establishment of
      appropriate models for discovering and testing therapy. The cytogenetic features
      of these tumors are also discussed. Classic karyotyping, loss of heterozygosity,
      fluorescent in situ hybridization, comparative genomic hybridization (CGH), and
      CGH-array analyses have shown that chromosomal numerical abnormalities and loss
      of genetic material at chromosomes 1p, 9p, 14q, and 22q are significantly
      associated with GIST malignancy and response to treatment. Furthermore, these
      regions constitute "hot" areas for finding candidate genes involved in the
      pathogenesis of GISTs. A deeper knowledge of these genetic aspects of GIST will
      provide a better understanding of this neoplasm that could translate into
      clinical practice.

PMID- 17193824
TI  - Gastrointestinal stromal tumors: differential diagnosis.
AB  - Availability of KIT tyrosine kinase inhibitors for specific treatment of GISTs
      has magnified the importance of accurate differential diagnosis of GIST from
      other tumors occurring in the GI tract and abdomen. The general problems in this
      distinction include histological mimicry of other mesenchymal tumors with GIST,
      occasional KIT-negativity of GIST, and KIT-positivity of non-GISTs. Up to 5% to
      10% gastric GISTs and <2% of intestinal GISTs can be KIT-negative. The
      identification of these tumors as GISTs is based on knowledge of the spectrum of
      GIST morphology, and can be supported by molecular diagnosis of KIT and PDGFRA
      mutations (the latter pertain to gastric tumors). True smooth muscle tumors (rare
      in GI tract except in esophagus and colon) can be separated from GISTs by the
      eosinophilic tinctorial quality of tumor cells, positivity for smooth muscle
      markers, and negativity for KIT. Desmoids can form large GIST-like masses, but
      are composed of spindled or stellate-shaped cells in a densely collagenous
      stroma. Negativity for KIT and nuclear positivity for beta-catenin are
      differentiating features. GI schwannomas, melanoma, and rare primary clear cell
      sarcoma are S100-positive, usually with characteristic histology. The latter two
      can be KIT-positive. KIT-positive non-GISTs include some sarcomas, especially
      angiosarcoma and Ewing sarcoma, extramedullary myeloid tumor, seminoma, and a few
      carcinomas, notably small cell carcinoma of lung. Spurious KIT-positivity, seen
      with some polyclonal KIT antibodies, has been a source of confusion leading to
      probable false-positive results in fibroblastic tumors and occasional other
      sarcomas, such as leiomyosarcomas. Integration of histological features with
      carefully standardized immunohistochemistry, supported by KIT and PDGFRA mutation
      analysis, is the cornerstone of state-of-the art differential diagnosis of GIST.
      To comprehensively capture all GISTs, KIT immunostains should be performed on all
      unclassified epithelioid and mesenchymal tumors of the abdomen. This is a US
      government work. There are no restrictions on its use.

PMID- 17193826
TI  - Clifford Kuhn, MD: healing with humor.

PMID- 17193825
TI  - Occurrence of other malignancies in patients with gastrointestinal stromal
      tumors.
AB  - Almost one-third of gastrointestinal stromal tumors (GISTs) are discovered
      incidentally during investigative or therapeutic procedures for unrelated
      diseases. In this regard, GISTs may coexist with different types of cancer,
      either synchronously or metachronously. The frequency of this association and the
      spectrum of neoplasms involved have not been sufficiently analyzed. We conducted
      a review of the literature and our own records for cases with sporadic GISTs and
      other malignancies, with emphasis on solid tumors. Neurofibromatosis 1 and Carney
      triad-associated tumors were excluded. Based on these data, there were 518
      cancers in 486 GIST patients among 4813 cases with informative data. The overall
      frequency of second tumors in different series varied from 4.5% to 33% (mean,
      13%). A total of 29 patients had multiple malignancies. GISTs of gastric location
      were most commonly involved with other neoplasms, reflecting their overall high
      frequency (60%) of all GISTs. The major types of GIST-associated cancers were
      gastrointestinal carcinomas (n=228; 47%), lymphoma/leukemia, (n=36; 7%), and
      carcinomas of prostate (n=43; 9%), breast (n=34; 7%), kidney (n=27; 6%), lung
      (n=26; 5%), female genital tract (n=25; 5%), and carcinoid tumors (n=13; 3%).
      Other cancers included soft tissue and bone sarcomas (n=15; 3%), malignant
      melanoma (n=12; 2%), and seminoma (n=6; 1%). Occurrence of collision tumors and
      metastases of carcinoma or sarcoma into a GIST (the latter noted in 4 cases) can
      be challenging diagnostic problems. The potential nonrandom association and
      causal relationship between GIST and other neoplasms remain to be investigated.

PMID- 17193827
TI  - The challenge of Medicare physician spending.

PMID- 17193828
TI  - HFMA's healthcare finance outlook 2007.

PMID- 17193829
TI  - A "best practices culture".

PMID- 17193830
TI  - Looking to rev up your revenue cycle?

PMID- 17193831
TI  - EHR value: don't expect what you don't plan for.
AB  - A value planning approach to electronic health record implementation involves six
      strategies for success: Value framework development. Value modeling. Benefit
      requirement identification and risk mitigation. Integrated planning. Value
      measurement. Organizing for value.

PMID- 17193832
TI  - Effective payment delay resolution: it's all in the details.
AB  - Health information management processes that should be carefully monitored to
      reduce payment delays include: Chart retrieval, assembly, and analysis. Loose
      paper filing. Transcription turnaround times. Timeliness of coding and
      abstracting. Coder productivity. Management of discharged not final billed.

PMID- 17193833
TI  - Health savings accounts: are you prepared?

PMID- 17193834
TI  - Making the grade with pay for performance: 7 lessons from best-performing
      hospitals.
AB  - Top-performing hospitals in pay-for-performance initiatives: Engage clinicians in
      quality improvement initiatives from the start of the planning process. Make high
      quality care the priority of the executive team. Have a dedicated quality,
      safety, and performance improvement department. Manage data collection
      effectively. Regularly share performance data with their staffs. Commit to
      sharing best practices. Celebrate the achievements of their healthcare teams.

PMID- 17193835
TI  - The 8 dimensions of quality.
AB  - Healthcare providers can better develop strategies for achieving and maintaining
      high-quality care by reviewing quality of care laws and metrics in relation to
      eight dimensions of quality: Reporting. Documentation. Quantity or access to
      care. Patient satisfaction. Provider reputation. Clinical processes. Utilization
      review. Medical necessity determinations.

PMID- 17193836
TI  - Building the business case for clinical quality.
AB  - Following are key findings of VHA Inc.'s Transformation of the ICU collaborative:
      Instead of improving patient outcomes, focusing too much on reducing costs as a
      performance improvement strategy only lays the groundwork for increased quality
      problems and higher costs. Improving quality can improve the bottom line, as long
      as there is patient demand. As a type, hospitals are organizations that
      characteristically have high fixed costs. The more customers such organizations
      can serve with the same investment, the greater their profits.

PMID- 17193837
TI  - Performance improvement: a "left brain meets right brain" approach.
AB  - Clinical analytics--the use of data to tie clinical quality to financial
      performance--strengthens hospitals' ability to compete in five ways: Enables
      clinical performance to be measured using clinical data. Supports a metric-driven
      culture. Allows hospitals to better manage regulatory initiatives. Enables
      hospitals to document the value of their IT investment. Provides a basis for
      redefining business strategy.

PMID- 17193838
TI  - Computerize your infection surveillance for improved patient care--and savings.
AB  - Kadlec Medical Center, in Richland, Wash., was able to reduce its nosocomial
      infection rate by 13 percent and save nearly dollar 576,000 in 15 months by:
      Working with the infection control department. Developing the business case for
      infection control initiatives. Conducting a preliminary financial analysis.
      Sharing data throughout the hospital--not just with the infection control
      department. Making the adoption of a computerized infection-tracking system a
      priority.

PMID- 17193839
TI  - A search for the "Holy Grail" of health care: a correlation between quality and
      profitability.
AB  - In a study by CHRISTUS Health, data from 18 acute care facilities revealed that
      numerous indicators of clinical quality were significantly correlated with
      measures of business success. Results suggest that timely and appropriate
      interventions, coupled with timely and complete documentation, are correlated
      with improved business performance. The correlations between quality and
      financial performance make intuitive sense based on the observation that
      diligence in clinical processes can produce better information to support
      financial processes.

PMID- 17193840
TI  - Pay-for-performance options in health care.
AB  - Pay for performance is expected to become widely implemented. Two critical issues
      in P4P are how much money is involved and what measures of performance the
      programs will pay for.

PMID- 17193841
TI  - Pay-for-performance checklists.

PMID- 17193842
TI  - An effective documentation strategy.

PMID- 17193843
TI  - Pricing transparency or smoke screen?

PMID- 17193844
TI  - Health care in crisis: is HIT the Rx?

PMID- 17193845
TI  - Why children's business development?

PMID- 17193846
TI  - Study: hospital professional and physician liability claims stabilizing.

PMID- 17193847
TI  - [Postoperative recurrence in Crohn's disease. Risk factors and methods of
      prevention].
AB  - Postoperative recurrences art frequent in Crohn's disease. Early recurrent
      lesions in the neoterminal ileum after ileocoIonic anastomosis is the most
      important risk factor for symptomatic recurrence of Crohn's disease after
      curative surgical resection. Others risk factors are ileocolonic anastomosis,
      perforating indication of surgery and smoking status. Many drugs have been
      evaluated for the prevention of clinical postoperative recurrence: Antibiotics,
      particularly metronidazole ornidazole, and a little benefice of mesalamine.
      Azathioprine and 6 mercaptopurine have been recently evaluated; with a not clear
      clinical effect for prevention of clinical recurrence after resection in Crohn's
      disease. Several authors have proposed an empiric strategy for the prevention of
      recurrence after curative resection, based essentially on existence and severity
      of early endoscopic recurrence.

PMID- 17193848
TI  - [Gastrointestinal stromal tumours: clinical and therapeutic features. A report of
      25 cases].
AB  - AIM: To evaluate the epidemiological clinical features and herapeutic results of
      gastrointestinal stromal tumour (GIST). PATIENTS AND METHOD: This retrospective
      study concerned 25 cases of gastrointestinal stromal tumour from January 1993 to
      December 2002. All patients have been operated and the diagnosis of GIST has been
      confirmed by histological and immunohistochemical study of pieces of resection or
      biopsies. RESULTS: Population include II men and 13 women with a mean age of 64
      years. Symptomatology was dominated by abdominal pain (54% of cases) and the
      digestive haemorrhage (46% of cases). A palpable mass has been found in 29% of
      cases. The tumour was gastric in 17 cases, small intestinal in 6 cases, colic in
      1 case and rectal in 1 case. A double gastric localization and small intestinal
      was found in 1 case. The mean tumour size was 8 cm (1 to 30 cm). A tumour
      resection has been achieved in 23 cases (96%), extended to neighbourhood organs
      in 2 cases. The morbidity was 12.5% and there was no operative mortality.
      Histologically, tumour was of low grade in 10 cases, high grade in 10 cases and
      unclassified in 5 cases. With a median follow up of 27 months (2 to 108), we
      observed 4 cases of loco-regional recurrence. Overall survival at 2 years was 74%
      for the whole population and 35% for the high grade. Independent prognostic
      factors recovered were the degree of malignancy (p = 0.01) and the local
      recurrence (p = 0.01). CONCLUSION: The treatment of the GIST is surgical.
      lymphadenectomy is superfluous. The new oral chemotherapies that inhibits
      Tyrosine Kinase seems to be promising.

PMID- 17193849
TI  - [Validation of a school children addictive behaviors questionnaire].
AB  - The aim was to develop and validate an addictive behaviors screening tool in
      school children. METHODOLOGY: A cross sectional study including a self
      administrated 223 item questionnaire developed in Arabic language. The
      questionnaire included identification of the student and seven life domains:
      school, family, addiction, relationships with peers, leisure and well being,
      risky behaviors and personality traits. N=854 high school children. of Monastir
      City. RESULTS: the questionnaire Alpha Cronbach's Coefficient ranged between 0.3
      and 0.8. Only items with a coefficient higher than 0.6 were maintained in the
      final version. The time reliability by using the Bland and Altman method 15 days
      after the first measure showed a Pearson's coefficient of 0.81. Validity
      evaluated by principal components analysis led to 3 independent factors
      consisting respectively in 20, 4 and 3 well correlated items: family, school and
      risky behaviors. CONCLUSION: validated version of the questionnaire consisted in
      102 items, easy to read and understand. This version doesn't require much time to
      be filled in and takes into consideration cultural particularities of the school
      children of Monastir. It could be considered as an interesting tool for both the
      assessment and the prevention of addictive behaviors in school.

PMID- 17193851
TI  - [Histopathological study of gastric polyps. A report of 65 cases].
AB  - In a retrospective study of the specimens of gastric polypectomy, carried out
      between January 1992 and December 2002, we analysed the demographic and
      histological aspects of 65 polyps. This study revealed hyperplastic polyps in
      66%, adenomatous lesions in 9.2%, Peutz-Jeghers polyps in 7.7%, inflammatory
      fibroid polyps in 6.15%, two cases of focal foveolar hyperplasia (3%), two cases
      of Brunner's gland heterotopia (3%), 1 pancreatic heterotopia (1.5%), 1 fundic
      gland polyp (1.5%) and 1 carcinoid tumor (1.5%). All adenomas and two Peutz
      Jeghers polyps include intraepithelial neoplasia. Moreover, we identified a case
      of Brunner's gland heterotopia, which contain a focus of plane tubular adenoma
      with high-grade intraepithelial neoplasia. Other lesions were found within the
      polyps or into the surrounding gastric mucosa, such as intestinal metaplasia and
      Helicobacter Pylori gastritis. This work allowed us to recommend complete removal
      of gastric polyps and the realization of biopsies of the nonpolypoid gastric
      mucosa in the search of intraepithelial neoplasia or other lesions with malignant
      potential.

PMID- 17193850
TI  - [Upper gastrointestinal endoscopy in neonates--experience of pediatric
      gastroenterology unit].
AB  - The aim of our study was to assess the frequency of the different lesions
      occurring as well as to precise indications of upper gastrointestinal endoscopy
      in neonates. METHOD: We have achieved a retrospective study about 128 neonatal
      gastrointestinal endoscopies. Three groups were constituted according to
      macroscopic findings: Group I: normal aspect (n=11); Group II: isolated
      esophagitis (n=19); Group III: esogastritis or gastroduodenitis or
      esogastroduodenitis (n=92). RESULTS: The neonates undergoing endoscopy for
      malaise were more frequent in group I than in group II and III, respectively
      36.5% versus 15.8% and 9.8% (P = 0.04). Digestive hemorrhage (hematemesis and/or
      melena) was more frequent in group III than in group II and I, respectively 90.2%
      versus 78.9% and 63.6% (P = 0.03). Digestive hemorrhage was in our study the main
      indication of upper gastrointestinal endoscopy in neonates (85.9%) which showed a
      macroscopic lesion in 93.5% of cases. CONCLUSION: Hematemesis and suspicion of
      esophagitis are good indications for upper gastrointestinal endoscopy in
      neonates.

PMID- 17193852
TI  - [Ureteral injuries in gynaecologic surgery].
AB  - Surgical injury to the ureter is an important problem that confronts the
      urologist, the gynaecologist and the general surgeon. We report 38 cases of
      iatrogenic ureteral injuries observed after gynaecological surgery between
      January 1972 and December 2004. Hysterectomy accounted for 22 injuries. Injuries
      were intra-operatively recognized in 3 cases and were treated immediately. In the
      case of lesions identified secondarily, a ureter-vesical implantation was
      performed in 66% of cases with a good result in 84% of them. Four patients
      required nephrectomy. We discuss the cicumstances of development, diagnosis
      approach and treatment of this lesion and review the literature about this
      subject.

PMID- 17193853
TI  - [Capsular distension and physical therapy in treatment of adhesive capsulitis].
AB  - OBJECTIVE: to evaluate the efficacy of capsular distension combined with
      intraarticular glucocorticoid injections and immediate physical therapy in the
      treatment of adhesive capsulitis. METHOD: a prospective open study of patients
      with adhesive capsulitis. Clinical and radiological criteria was used for
      diagnosis. Clinical evaluation was realized before treatment, at the end of the
      treatment, after 1 month, 3 months and 6 months. It carried on: the measure of
      pain and handicap intensity by an Visual Analogue Scale, the algo-functional
      score of Constant, the measure of passive articular mobilities. We ended in a
      success of the treatment when the visual analogue scale of handicap < 30, the
      score of Constant >70, the passive abduction >90 and the external rotation (RE)
      >45 degrees. RESULTS: 19 patients were included, mean aged 56 years with capsular
      retraction evolving on average for 8.5 months. The parameters of evaluation of
      pain function and handicap improved significantly since the end of treatment.
      This improvement continued until 6 months after the treatment. Earning in
      articular amplitudes was significant since the end of treatment for forward
      extension and internal rotation. However, the improvement in abduction and
      internal rotation was significant only at 3 months. In spite of this early
      significant improvement in external rotation, 6 patients had an important
      limitation of the RE (<20 degrees). A subacromial bursography with steroid
      injection was proposed to them because subacromial bursa is almost consistently
      involved by retraction. Only, 4 patients among them accepted it. Out come was
      favorable in every case with a external rotation >45 degrees at I month of the
      treatment. The rate of success which was only 47.3% at the end of the treatment,
      is crossed in 73.6% at 1 month and reaches 89.4% at 6 months. CONCLUSION: The
      therapeutic association capsular distension, intraarticular steroid injections
      and physical therapy allows to shorten the course of adhesive capsulitis. Burso
      infiltration seems to be effective as therapeutic complement in case of
      persistence of an articular limitation.

PMID- 17193854
TI  - [Fibrocystic mastopathy and cancer of the breast. About 111 cases].
AB  - OBJECTIVE: Our aim was to identify the predictive factors of degeneration of the
      fibrocystic mastopathy. METHODS: This work is a retrospective survey of 111
      observations of isolated fibrocystic mastopathies or associated to a breast
      cancer among 542 women admitted for tumor of the breast during one period of 13
      active years from 1991 to 2003. The diagnosis has been gotten by anatomo
      pathologic exam in 95.5% (106 cas) on the operative piece and 4.5% (5 cas) on a
      material of biopsy. RESULTS: The fibrocystic mastopathy represented 30% of the
      set of the benign tumors of the breast. They were associated to a breast cancer
      in 45 cases (40.5%). The isolated benign fibrocystic mastopathy was observed in
      66 cases with a middle age of 37 years, whereas the shapes associated to a breast
      carcinoma were noted in 45 cases. The middle age was 53 years. The non
      proliferative fibrocystic mastopathy is the most frequent histological type and
      represent 54.6% of the cases. The proliferative form with atypies was observed at
      21 women (46.8%). The carcinoma the more frequently associated to the fibrocystic
      mastopathy was the infiltrating canalled carcinoma in 91% of cases, with a
      predominance of the II rank (SBR). CONCLUSION: The discovery of a mastopathy must
      search a luteal failure and risk factors of breast cancer notably a proliferative
      shape of mastopathy with atypies.

PMID- 17193855
TI  - [Psychiatric morbidity and quality of life in Vitiligo: a case controlled study].
AB  - The aims of this study were to value the psychiatric morbidity and its influence
      on the quality of life of patients with vitiligo. METHODS: It was a case
      controlled study bearing on 60 outpatients with vitiligo examined in the
      department of Dermatology of the University Hospital of Monastir, compared to 60
      controls matched according to age and sex, among outpatients with others
      dermatologic disorders as warts or superficial mycoses. The assessment consisted
      in the epidemiological and clinical evaluation, including these questionnaires:
      the Dermatology Life Quality Index (DLQI), the Montgomery and Asberg Depression
      Rating Scale (MADRS) and the Hamilton Anxiety Appreciation Scale (HAMA). RESULTS:
      Mean scores of depression in the MADRS and anxiety in the HAMA were significantly
      more elevated in patients with vitiligo (p = 0.0005). Quality of life was
      significantly more altered in patients with vitiligo: DLQI mean score = 9.4 +/-
      17.1 versus 2.5 +/- 1.0 among the controls (p < 0.0001). A positive correlation
      has been noted between the quality of life scores and the MADRS depression scores
      (p < 10(-10)) and the HAMA anxiety scores (p < 10(9)). CONCLUSION: The quality of
      life decrease in patients with vitiligo is especially related to the psychiatric
      comorbidity underlining the multidisciplinary therapeutic necessity including the
      psychotherapeutic approach.

PMID- 17193856
TI  - [Epidemiologic profile of the newborn of unmarried mother in Bizerta. About 187
      cases].
AB  - The aim of this study is to establish the epidemiologic profile of 187
      illegitimatepregnancies compared topregnancies from married mothers. PATIENTS AND
      METHODS: A transversal retrospective study was carried out in Bizerta from 1990
      to 2003. The witness group was constitued by women whose gonna delivery at the
      same period with p < 0.05. RESULTS: Throughout this study, we have found that
      single mothers with a mean age of 24 years, are younger than married mothers and
      has a rural origin and primiparous status. Pregnancy was not followed-up in 70.6%
      vs. 1.6% and maternal serology was done in 17% vs. 96.8%. 38.4% of new-borns of
      single mothers were hospitalised (vs. 13.2% in the group witness) for materno
      foetal infection (14.4%), respiratory distress syndrome (11.7%), prematurity
      (9.6%) and intra-uterine growth delay (2.1%). The mortality rate in newborns of
      single mothers was 5.3%. CONCLUSION: Illegitimate pregnancy is not well followed
      up, worst to live and comport a risk for the health and mental in mothers and
      newborns.

PMID- 17193858
TI  - [Detection of DNA human cytomegalovirus of a molecular methods: hybrid capture
      DNA CMV by immunocompromised].
AB  - Human cytomegalovirus (HCMV), a member of the beta-virus herpes family, is a
      ubiquitous human pathogen. After a primary infection, HCMV establishes life
      latency. HCMV rarely causes symptomatic disease in an immunocompetent host,
      however, it is a major cause of infectious morbidity and mortality in
      immunocompromised individuals and developing fetuses. The HCMV genome consists of
      240 kbp of double stranded DNA. Early diagnosis molecular of CMV infection is
      important. The objective of this study was to develop a molecular methods:
      Quantitative Hybrid capture for the detection of DNA CMV. We present results for
      200 immunocompromised collected from 1999 to 2003 (122 men and 78 women, whom
      mean age was 35 years). Our results showed that 25% of women and 36% of men were
      positif for hybrid capture DNA CMV. This simple test (cold probe) provide
      quantitative and fast results. Also the efficacity of anti-CMV therapy can be
      followed. More over, in contrary with pp65-antigenemia assay and CMV PCR, this
      test can be managed on biopsy sample.

PMID- 17193857
TI  - [Fluconazole and treatment of onychomycosis. About 86 cases].
AB  - Systemic treatment of onychomycosis is based these last years on the new drug
      utilization aiming to decrease the length of the treatment and secondary effects
      particularly with fluconazole. The aim of our study is to determine the
      efficiency and the tolerance of the fluconazole (Funzol) managed to the dose of
      150 mg per week in the treatment of onychomycosis. It is a multicentric and
      prospective study done to different department of dermatology in Tunisia. Are
      included adult patients with clinical and mycologic documented onychomycosis.
      They are treated during 12 to 24 weeks for the fingernail and 24 to 36 weeks for
      the toenail. The assessment of the efficiency and the tolerance of the drug was
      clinic and biologic. During this survey, 86 patients are included, 55 female and
      31 male with mean age of 43.5 years. Onychomycosis seat to hands in 30 cases
      (34.8%) with a predominance of Candida species (73%), to toes in 68 cases (79%)
      witch due in 85% of cases to dermatophytic agent (85%). At 6 months, clinical
      cure rate is observed in 51% of cases. After 9 months, at the end of therapy, 84%
      of patients were judged clinical successes and culture was negative in 82% of
      cases. Some minimal secondary effects are signalled in 11% of cases to 6 weeks
      and 10% to 12 weeks not justifying the stop of the treatment. So this study
      confirms the efficiency and the good tolerance of fluconazole in the treatment of
      onychomycosis.

PMID- 17193859
TI  - Food intake and high density lipoprotein cholesterol levels changes during
      ramadan fasting in healthy young subjects.
AB  - During the holy month of Ramadan, it is obligatory for all adult healthy Muslims
      to abstain from food, drink and smoking each day from dawn to sunset. The aims of
      our study were to evaluate the effects of Ramadan fasting on plasma lipids,
      lipoproteins and the change of food consumption in healthy subjects. Thirty young
      healthy and normal weighted adults (9 males and 21 females) were evaluated during
      three periods: 3 weeks before Ramadan (T0); the 4th week of Ramadan (T1) and 3
      weeks after the end of Ramadan (T2). Main Clinical and biological parameters
      investigated were: body weight, blood glucose, plasma triglycerides (TG), plasma
      total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and. low
      density lipoprotein cholesterol (LDL-c) Body weight, and blood glucose were
      unchanged. There was a significant increase of the mean daily caloric intake, the
      lipids intake particularly mono-unsaturated and poly-unsaturated fatty acids (p <
      0.001) and cholesterol intake (p < 0.001) during Ramadan with a decrease of the
      meal frequency. There was also a significant increase of plasma total cholesterol
      and HDL-cholesterol. The most striking finding was a significant increase in the
      HDL-Cholesterol during Ramadan +20% (p < 0.02). This increase was lost after
      Ramadan. Fasting Ramadan affects beneficially serum lipoprotein metabolism in
      young adult healthy subjects with an increase of HDL-cholesterol.

PMID- 17193860
TI  - [What is your diagnosis? Epiploic appendicitis also called torsion of an epiploic
      fringe of the right colon].

PMID- 17193861
TI  - [Norwegian scabies, a rare diagnosis in Tunisia].
AB  - Norwegian scabies is a particular form of scabies, rarely reported in Tunisia. It
      habitually occurs in immunocompromised hosts, with prolonged immunosuppressive
      therapy, congenital immune disease, HIV-1 infection or neoplasm. We report an
      observation of norwegian scabies, occuring in a woman with prolounged systemic
      corticosteroid therapy. OBSERVATION: A 65-year-old woman, with a long history of
      obstructive bronchoneumopathy and bronchiectasis, treated with systemic
      corticosteroids for 5 years, was referred with a mild pruriginous and scaly
      erythroderma. This dermatosis developed within 5 months, with fever and impairing
      of health. Skin parasitological exams showed a massive infestation by sarcoptes.
      Histologic findings revealed multiple sarcoptes scabiei and eggs in the stratum
      corneum. The patient was treated with benzyl benzoate during 48 hours. She died
      rapidly with acute respiratory distress. DISCUSSION: basing on this observation
      of norwegian scabies occuring in an old immunocompromised woman, we put the
      accent on this particular form of scabies, often misappreciated, and incite to
      practice skin and nail parasitological exams in case of mild pruriginous, chronic
      scaly erythroderma. developing in immunocompromised patients.

PMID- 17193862
TI  - [Hyperlipidaemia associated to inaugurated diabetic ketoacidosis].
AB  - Severe hyperlipidaemia in presenting diabetic ketoacidosis was rarely reported in
      child. We report the case of a three-year-old girl with presenting diabetic
      ketoacidosis. Family history was negative for hyperlipidaemia. Serum was creamy
      pink in gross appearance. The child has a hyperlipidaemia with serum
      triglycerides 18.5 mmol/l and serum cholesterol 13.8 mmol/l. The hyperlipidaemia
      disappeared with insulin therapy within seven days. We study the clinical,
      laboratory, pathogenic and evolution features of this uncommon trouble in
      diabetic children.

PMID- 17193863
TI  - [Q fever endocarditis: a case report].
AB  - Do we bring back the observation of a patient aged of 42 years having a mitro
      aortic valvulopathy who present since 3 months a level III dyspnea, a fever to 39
      degrees C, a change of the general state and a splenomegaly. To the chest x-ray
      we note a pulmonary parenchymatous focus. Echocardiography puts in evidence a
      mitral illness to stenosis predominance and an aortic illness complicated of a
      graft bacterial with an abscess of the mitro-aortic trigone. Haemocultures were
      negative and the serology of the Rickettsia was positive. The diagnosis of
      infective endocarditis to Coxiella Burnetii is kept and is the patient put under
      Doxycycline 200 mg/j, Hydroxychloroquine 2 cp/j and Ofloxacine 400 mg/j. Will the
      two first antibiotics be pursued to the 18th month. The patient benefited, after
      20 days of three antibiotics therapy, of a duplicate aortic and mitral
      replacement with simple following.

PMID- 17193864
TI  - [Idiopathic chylothorax: usefulness of aetiologic survey and the follow-up].
AB  - Chylothorax is an uncommon condition. It's characterized by the presence of chyle
      in the pleura. The most common causes are malignancy and trauma. When an
      underlying cause is excluded, the chylothorax is called idiopathic. We report a
      case of a 68 aged woman, admitted for abundant chylothorax. Thoraco-abdominal
      computed tomography, magnetic resonance imaging of the chest and thoracotomy
      showed no lesion of the lymphatic duct. Fibrothorax has developed after
      pleurodesis. Stable clinical and radiological condition was noticed during 3
      years. We discuss the difficulty in the exclusion of a malignancy and the
      necessity of the follow up for these patients.

PMID- 17193865
TI  - [Severe community acquired pneumonia due to Staphylococcus aureus in children.
      About two cases].
AB  - The staphylococcal pneumonia is the prerogative of the infant but rare cases were
      observed in the childhood. We report the observation of two children aged
      respectively of six years and three years and a half having presented a
      particular form of severe staphylococcal pneumonia apart from any context of
      immunodepression. The identification of the particular strains producing toxins
      Like the Panton and Valentine leukocidin constitutes the first stage of the
      comprehension of this atypical form of pneumonia. Through these observations and
      with a review of literature we underline the specific clinical and biological
      aspects of this form.

PMID- 17193866
TI  - [Screening and management of coronary artery disease in diabetic patients].
AB  - Diabetes represents as independent risk factor for coronary artery disease (CAD)
      and the prognosis in term of survival rates is worse for diabetic patients who
      have CAD with report to those with CAD but no diabetes. The coronary artery
      disease in diabetes has specificities and, in particular, more extensive
      atherosclerosis. Diabetic patients are also more frequently asymptomatic. Due to
      the extreme complexity of ischemic vascular disease in patients with diabetes, an
      optimal therapeutic strategy is based on the correction of elevated blood glucose
      and lipid levels, of blood pressure, of platelet and coagulation abnormalities.
      Diabetic patients benefit from secondary prevention by drug therapy(aspirin,
      lipid lowering with statines, beta blocker and ACE inhibitors) to the same extent
      as, or more than, non-diabetic patients. Both percutaneous and surgical
      myocardial revascularization have been proved equally effective for CAD treatment
      in diabetes. A recent randomized trial has shown a significantly improved outcome
      after surgical revascularization. But, the effects of drug-eluting stents, which
      dramatically decrease the incidence of re-stenosis, seem promising.

PMID- 17193867
TI  - A comparison of serratus anterior muscle activation during a wall slide exercise
      and other traditional exercises.
AB  - STUDY DESIGN: Single-group repeated-measures design. OBJECTIVES: To investigate
      the ability of the wall slide exercise to activate the serratus anterior muscle
      (SA) at and above 90 degrees of humeral elevation. BACKGROUND: Strengthening of
      the SA is a critical component of rehabilitation for patients with shoulder
      impingement syndromes. Traditional SA exercises have included scapular
      protraction exercises such as the push-up plus. These exercises promote
      activation of the SA near 90 degrees of humeral elevation, but not in positions
      above 90 degrees where patients typically experience pain. METHODS AND MEASURES:
      Twenty healthy subjects were studied performing 3 exercises: (1) wall slide, (2)
      plus phase of a wall push-up plus, and (3) scapular plane shoulder elevation.
      Three-dimensional position of the thorax, scapula, and humerus and muscle
      activity from the SA, upper and lower trapezius, and latissimus dorsi were
      recorded. The magnitudes of activation for each muscle at 90 degrees, 120
      degrees, and 140 degrees of humeral elevation were quantified from EMG records.
      Repeated-measures analyses of variance were used to determine the degree to which
      the different exercises activated the SA at the 3 humeral positions. RESULTS: The
      intensity of SA activity was not significantly different between the 3 exercises
      at 90 degrees of humeral elevation (P = .40). For the wall slide and scapular
      plane shoulder elevation exercises, SA activity increased with increasing humeral
      elevation angle (P = .001), with no significant differences between the 2
      exercises (P = .36). CONCLUSION: The wall slide is an effective exercise to
      activate the SA muscle at and above 90 degrees of shoulder elevation. During this
      exercise, SA activation is not significantly different from SA activation during
      the push-up plus and scapular plane shoulder elevation, 2 exercises previously
      validated in the literature.

PMID- 17193868
TI  - Star Excursion Balance Test as a predictor of lower extremity injury in high
      school basketball players.
AB  - STUDY DESIGN: Prospective cohort. OBJECTIVE: To determine if Star Excursion
      Balance Test (SEBT) reach distance was associated with risk of lower extremity
      injury among high school basketball players. BACKGROUND: Although balance has
      been proposed as a risk factor for sports-related injury, few researchers have
      used a dynamic balance test to examine this relationship. METHODS AND MEASURES:
      Prior to the 2004 basketball season, the anterior, posteromedial, and
      posterolateral SEBT reach distances and limb lengths of 235 high school
      basketball players were measured bilaterally. The Athletic Health Care System
      Daily Injury Report was used to document time loss injuries. After normalizing
      for lower limb length, each reach distance, right/left reach distance difference,
      and composite reach distance were examined using odds ratio and logistic
      regression analyses. RESULTS: The reliability of the SEBT components ranged from
      0.82 to 0.87 (ICC3,1) and was 0.99 for the measurement of limb length. Logistic
      regression models indicated that players with an anterior right/left reach
      distance difference greater than 4 cm were 2.5 times more likely to sustain a
      lower extremity injury (P<.05). Girls with a composite reach distance less than
      94.0% of their limb length were 6.5 times more likely to have a lower extremity
      injury (P<.05). CONCLUSIONS: We found components of the SEBT to be reliable and
      predictive measures of lower extremity injury in high school basketball players.
      Our results suggest that the SEBT can be incorporated into preparticipation
      physical examinations to identify basketball players who are at increased risk
      for injury.

PMID- 17193869
TI  - The use of real-time ultrasound imaging for biofeedback of lumbar multifidus
      muscle contraction in healthy subjects.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To determine if the
      provision of visual biofeedback using real-time ultrasound imaging enhances the
      ability to activate the multifidus muscle. BACKGROUND: Increasingly clinicians
      are using real-time ultrasound as a form of biofeedback when re-educating muscle
      activation. The effectiveness of this form of biofeedback for the multifidus
      muscle has not been reported. METHODS AND MEASURES: Healthy subjects were
      randomly divided into groups that received different forms of biofeedback. All
      subjects received clinical instruction on how to activate the multifidus muscle
      isometrically prior to testing and verbal feedback regarding the amount of
      multifidus contraction, which occurred during 10 repetitions (acquisition phase).
      In addition, 1 group received visual biofeedback (watched the multifidus muscle
      contract) using real-time ultrasound imaging. All subjects were reassessed a week
      later (retention phase). RESULTS: Subjects from both groups improved their
      voluntary contraction of the multifidus muscle in the acquisition phase (P<.001)
      and the ability to recruit the multifidus muscle differed between groups (P<.05),
      with subjects in the group that received visual ultrasound biofeedback achieving
      greater improvements. In addition, the group that received visual ultrasound
      biofeedback retained their improvement in performance from week 1 to week 2
      (P>.90), whereas the performance of the other group decreased (P<.05).
      CONCLUSION: Real-time ultrasound imaging can be used to provide visual
      biofeedback and improve performance and retention in the ability to activate the
      multifidus muscle in healthy subjects.

PMID- 17193870
TI  - Scapular angular positioning at end range internal rotation in cases of
      glenohumeral internal rotation deficit.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: Investigate the
      relationship between glenohumeral internal rotation range-of-motion deficit and 3
      dimensional scapular angular positioning during active arm movements in
      participants with recent participation in overhead sports activity. BACKGROUND:
      Subacromial impingement is one of the most common shoulder pathologies and is
      multifactorial in etiology. Posterior glenohumeral joint capsule tightness has
      been theorized to contribute to one potential causal factor: abnormal scapular
      positioning. METHODS AND MEASURES: Twenty-three subjects, who had participated in
      competitive sports involving overhead activity within the last 5 years, were
      categorized into 2 groups based on the degree of glenohumeral internal rotation
      deficit (20% deficit threshold). Scapular angular positioning of subjects
      performing shoulder internal rotation from 90 degrees flexion and abduction
      shoulder positions was evaluated using 3-dimensional electromagnetic surface
      tracking. Additional sensors monitored trunk and humeral motion. Scapular
      position data at end range glenohumeral internal rotation, along with
      glenohumeral internal rotation range of motion measurements, were used to analyze
      the relationship between glenohumeral internal rotation deficit and scapular
      position using 2-way ANOVA and regression analyses. RESULTS: The internal
      rotation deficit group had significantly greater scapular anterior tilt (9.2
      degrees difference, P = .04) across positions, as compared to the control group.
      Regression analysis demonstrated a significant association between glenohumeral
      internal rotation deficit and scapular position (tilting) during flexed internal
      rotation (r(2) = 0.37, P = .03) and for scapular position (anterior tilting and
      upward rotation) during abducted internal rotation (r = 0.35, P = .036).
      CONCLUSIONS: These findings demonstrate a significant relationship between
      glenohumeral internal rotation deficit and abnormal scapular positioning,
      particularly increased anterior tilt. This relationship identifies a possible
      mechanism for development of excessive scapular anterior tilt.

PMID- 17193871
TI  - Knee joint stiffness in individuals with and without knee osteoarthritis: a
      preliminary study.
AB  - STUDY DESIGN: Descriptive, case-matched comparison. OBJECTIVES: To compare the
      knee joint stiffness and damping coefficients of individuals with knee
      osteoarthritis (KOA) to those of age- and gender-matched individuals without KOA.
      A secondary purpose was to investigate relationships between these coefficients
      and complaints of stiffness in individuals with KOA. BACKGROUND: KOA is a leading
      cause of disability, and stiffness is a common complaint in individuals with KOA.
      Yet the most common method of assessing knee joint stiffness is through a self
      report questionnaire. METHODS AND MEASURES: Stiffness and damping coefficients at
      the knee were calculated in 10 volunteers (mean age +/- SD, 64.1+/-15.5 years)
      with KOA and compared to coefficients from age-and gender-matched individuals
      without KOA, collected in a previous study (mean age +/- SD, 62.1+/-13.9 years).
      Stiffness and damping coefficients were calculated from the angular motion of the
      knee during a relaxed oscillation. Spearman correlation coefficients were
      calculated between stiffness and damping coefficients and WOMAC (Western Ontario
      and McMaster Universities Osteoarthritis Index) scores for subjects with KOA.
      RESULTS: Independent 2-tailed t tests revealed significantly larger damping
      coefficients (P = .035) among those with KOA (95% CI, 0.10-2.32 Nm s/rad).
      Spearman rank correlations revealed a significant positive relationship (r = .85,
      P = .003) between the damping coefficient and the stiffness subscore of the
      WOMAC. CONCLUSION: This study offers preliminary data demonstrating the
      feasibility of measuring stiffness and damping coefficients in individuals with
      KOA. Additionally, the damping coefficient is increased in people with KOA when
      compared to age- and gender-matched individuals without KOA. The damping
      coefficient appears to be associated with the complaints of stiffness reported by
      the WOMAC.

PMID- 17193872
TI  - Comparison of different structural foot types for measures of standing postural
      control.
AB  - STUDY DESIGN: Matched group comparison of 3 subject groups with 3 different foot
      structures for force plate and clinical measures of postural control. OBJECTIVES:
      To determine if subjects with different weight-bearing foot structure would
      demonstrate differences in static standing postural control, and to determine the
      reliability of study procedures. BACKGROUND: Weight-bearing foot structure may
      influence postural control either because of a decreased base of support
      (supinated foot structure) or because of passive instability of the joints of the
      foot (pronated foot structure). METHODS AND MEASURES: Young adults were
      categorized based on weight-bearing foot structure into neutral, pronated, or
      supinated groups (15 subjects per group). Postural control in single-limb stance
      with eyes closed was assessed using force plate measures and by measuring
      duration of single-limb stance on a firm floor and on a balance pad. Force plate
      measures were normalized center-of-pressure average speed; and standard deviation
      and maximum displacement in the anterior-posterior and medial-lateral directions.
      RESULTS: Individuals in the supinated group had significantly greater center-of
      pressure average speed, greater maximum displacement in the anterior-posterior
      direction, and greater SD and maximum displacement in the medial-lateral
      direction than individuals in the neutral group. The individuals in the pronated
      group had significantly greater SD and maximum displacement in the anterior
      posterior direction, used more trials to complete force plate testing, and had
      shorter single-limb stance duration than those in the neutral group. CONCLUSION:
      Individuals with pronated feet or supinated feet have poorer postural control
      than individuals with neutral feet, but perhaps through different mechanisms.

PMID- 17193874
TI  - Researchers and clinicians: a growing divide or narrowing gap?

PMID- 17193873
TI  - Sagittal plane knee motion in the ACL-deficient knee during body weight shift
      exercises on different support surfaces.
AB  - STUDY DESIGN: Experimental design with group comparisons. OBJECTIVES: To compare
      anterior tibial translation and muscle activity among different exercises for
      early weight-bearing and neuromuscular training in individuals with a unilateral
      anterior cruciate ligament (ACL) injury and in uninjured controls. BACKGROUND:
      The effects of exercise and activity on tibial translation must be taken into
      consideration during rehabilitation after ACL injury. METHODS AND MEASURES:
      Twelve patients with an ACL-deficient knee and 12 age- and gender-matched
      controls participated in the study. Sagittal tibial translation and muscle
      activity were registered during the Lachman test (static translation) and 4 body
      weight shift exercises (dynamic translation). A Student t test with Bonferroni
      correction and analysis of variance were used for the statistical analysis.
      RESULTS: Forward-backward body weight shift exercise resulted in smaller anterior
      tibial translation compared to body weight shift from side to side. Analysis of
      EMG activity could not explain this difference in anterior tibial translation.
      The amount of anterior tibial translation or EMG activity did not change when the
      exercises were performed on a trampoline compared to a firm surface. CONCLUSIONS:
      Forward-backward weight shifting may be preferable in initial rehabilitation
      after ACL injury compared to body weight shift from side to side.

PMID- 17193875
TI  - Mutation and virulence assessment of chromosomal genes of Rhodococcus equi 103.
AB  - Rhodococcus equi can cause severe or fatal pneumonia in foals as well as in
      immunocompromised animals and humans. Its ability to persist in macrophages is
      fundamental to how it causes disease, but the basis of this is poorly understood.
      To examine further the general application of a recently developed system of
      targeted gene mutation and to assess the importance of different genes in
      resistance to innate immune defenses, we disrupted the genes encoding high
      temperature requirement A (htrA), nitrate reductase (narG), peptidase D (pepD),
      phosphoribosylaminoimidazole-succinocarboxamide synthase (purC), and superoxide
      dismutase (sodC) in strain 103 of R. equi using a double-crossover homologous
      recombination approach. Virulence testing by clearance after intravenous
      injection in mice showed that the htrA and narG mutants were fully attenuated,
      the purC and sodC mutants were unchanged, and the pepD mutant was slightly
      attenuated. Complementation with the pREM shuttle plasmid restored the virulence
      of the htrA and pepD mutants but not that of the narG mutant. A single-crossover
      mutation approach was simpler and faster than the double-crossover homologous
      recombination technique and was used to obtain mutations in 6 other genes
      potentially involved in virulence (clpB, fadD8, fbpB, glnA1, regX3, and sigF).
      These mutants were not attenuated in the mouse clearance assay. We were not able
      to obtain mutants for genesfurA, galE, and sigE using the single-crossover
      mutation approach. In summary, the targeted-mutation system had general
      applicability but was not always completely successful, perhaps because some
      genes are essential under the growth conditions used or because the success of
      mutation depends on the target genes.

PMID- 17193876
TI  - Immunohistochemical detection of 3 viral infections in paraffin-embedded tissue
      from mink (Mustela vison): a tissue-microarray-based study.
AB  - Immunohistochemical (IHC) assays were developed and tested for the detection of 3
      viral infections in archived paraffin-embedded mink tissue. Specimens had been
      obtained from mink with diagnoses of acute Aleutian disease (AD), mink parvoviral
      enteritis (MVE), or canine distemper (CD) made by means of routine diagnostic
      procedures. To improve the efficiency and reduce the costs of IHC analyses,
      tissue microarray (TMA) technology was used. Representative cores 2 mm in
      diameter from each tissue specimen and from positive- and negative-control
      specimens were collected in a TMA block. Immunohistochemical reactions to viral
      antigens were assessed and graded. Positive reactions were found in 91% of the 32
      specimens from mink with AD, 53% to 80% of the 60 specimens from mink with MVE,
      and all 66 of the specimens from mink with CD. To validate the use of TMAs, the
      IHC methods were applied to whole-mount paraffin-embedded sections of 10 of the
      positive specimens for each disease, together with whole-mount sections of small
      intestine and lung tissue from 2 healthy mink. The IHC grading of the TMA cores
      and the whole-mount sections from the same animal corresponded completely. These
      results suggest that IHC demonstration of viral antigen allows rapid and reliable
      diagnosis of the 3 viral infections in mink and is a potential supplement to
      histologic diagnostic procedures. The TMA technique proved useful for screening
      large numbers of samples for expression of specific viral antigens, while
      reducing overall costs.

PMID- 17193877
TI  - Detection and molecular typing of Streptococcus suis in tonsils from live pigs in
      France.
AB  - Streptococcus suis is an important pathogen of swine, causing meningitis,
      arthritis, polyserositis, septicemia, and sudden death in weaning piglets as well
      as fattening pigs. Recently, 3 molecular tests have been developed in our
      laboratory: a multiplex polymerase chain reaction (m-PCR) assay for the detection
      of S. suis species and serotypes 2 and 1/2, and 2 molecular typing methods,
      pulsed-field gel electrophoresis and an approach based on PCR amplification of a
      fragment of rRNA genes, including a part of the 16S and 23S genes and the 16S-23S
      rDNA intergenic spacer region (ISR), followed by restriction fragment length
      polymorphism (RFLP) analysis (ISR-RFLP). In the present study, we used these
      tests to analyze tonsil samples from clinically healthy pigs and to identify
      individual isolates of S. suis during epidemiologic investigations of 8 related
      herds with a history of septicemia caused by S. suis serotype 2. Capsular typing
      showed that 58% of the strains were nontypable. Of the 17 serotypes present,
      serotype 22 was the most prevalent. In the 7 farms without clinical signs on the
      day of sampling, we detected S. suis serotype 2 or 1/2, or both, in less than 5%
      of the pigs by m-PCR or by bacteriologic culture. In the 8th farm, on which 2
      pigs had clinical signs of septicemia on the day of sampling, we detected S. suis
      serotype 2 or 1/2, or both, by m-PCR in the tonsils of 40% of fattening pigs (21
      wk old) that lacked symptoms. Molecular typing of the serotype 2 strains showed a
      common origin of contamination in these herds, given that 1 pattern (C1) was
      detected in the isolates from 6 of the 8 herds. However, up to 4 patterns were
      associated with septicemia and sudden death. Several patterns of S. suis serotype
      2 can be responsible for disease in the same herd. These molecular tools may be
      useful for confident studies of the transmission of S. suis, thereby contributing
      to the control of S. suis infection.

PMID- 17193878
TI  - Influence of isolate pathogenicity on the aerosol transmission of Porcine
      reproductive and respiratory syndrome virus.
AB  - The objectives of this study were to evaluate the role of isolate pathogenicity
      in the aerosol transmission of Porcine reproductive and respiratory syndrome
      virus (PRRSV) and to determine whether PRRSV could be detected in air samples. To
      assess transmission, we exposed naive recipient pigs to aerosols from pigs
      inoculated with PRRSV MN-30100, an isolate of low pathogenicity, or MN-184, a
      highly pathogenic isolate. Blood samples and nasal-swab samples were collected
      from the inoculated pigs during the exposure period and tested for the presence
      of PRRSV RNA by quantitative (real-time) reverse-transcriptase polymerase chain
      reaction (RT-PCR); the amount of RNA was expressed as the median tissue culture
      dose per milliliter (TCID50/mL). The recipient pigs were clinically evaluated for
      14 d after exposure and tested on days 7 and 14 by qualitative RT-PCR and enzyme
      linked immunosorbent assay (ELISA). To prove the presence of PRRSV in aerosols,
      air samples were collected from each recipient-pig chamber by means of an air
      sampler. The PRRSV RNA concentrations were significantly higher (P = 0.01) in the
      blood samples from the pigs infected with PRRSV MN-184 than in the blood samples
      from those infected with PRRSV MN-30100; however, the concentrations in the nasal
      swab samples were not significantly different (P = 0.26). Recipient pigs exposed
      to aerosols from pigs infected with PRRSV MN-184 became infected, whereas those
      exposed to aerosols from pigs infected with PRRSV MN-30100 did not; the
      difference in transmission rate was significant at P = 0.04. We detected PRRSV MN
      184 RNA but not PRRSV MN-30100 RNA in air samples by PCR. Under the conditions of
      this study, PRRSV isolate pathogenicity may influence aerosol transmission of the
      virus.

PMID- 17193880
TI  - Evidence for degradation of abnormal prion protein in tissues from sheep with
      scrapie during composting.
AB  - This study investigated whether the abnormal prion protein (PrP(Sc)) in tissues
      from sheep with scrapie would be destroyed by composting. Tissues from sheep
      naturally infected with scrapie were placed within fiberglass mesh bags and
      buried in compost piles for 108 d in experiment 1 or 148 d in experiment 2. The
      temperature in the compost piles rose quickly; it was above 60 degrees C for
      about 2 wk and then slowly declined to the ambient temperature. Before
      composting, PrPSc was detected in all the tissues by Western blotting. In
      experiment 1, PrPsc was not detected after composting in the tissue remnants or
      the surrounding sawdust. In experiment 2, 1 of 5 specimens tested negative after
      composting, whereas PrP(Sc) was detected in the other 4 bags, though in reduced
      amounts compared with those before composting. Tissue weights were reduced during
      composting. Analysis of the tissue remnants for microbial 16S ribosomal DNA
      demonstrated that there were more diverse microbes involved in experiment 1 than
      in experiment 2 and that the guanine and cytosine content of the microbial 16S
      DNA was higher in the specimens of experiment 1 than in those of experiment 2,
      which suggests greater dominance of thermophilic microbes in experiment 1. These
      results indicate that composting may have value as a means for degrading PrP(Sc)
      in carcasses and other wastes.

PMID- 17193879
TI  - Evaluation of equine papillomas, aural plaques, and sarcoids for the presence of
      Equine papillomavirus DNA and Papillomavirus antigen.
AB  - Immunohistochemical (IHC) testing and electron microscopy have implicated
      Papillomavirus (PV) as the etiologic agent for equine papillomas and aural
      plaques, but Equine papillomavirus (EPV) DNA has yet to be demonstrated in these
      lesions by polymerase chain reaction (PCR). The purpose of this study was to
      evaluate formalin-fixed, paraffin-embedded tissues from naturally occurring cases
      of equine papillomas, aural plaques, and sarcoids for the presence of EPV DNA by
      means of PCR and for the presence of PV antigen by means of IHC testing. We used
      EPV-specific primers that amplified a region of 384 base pairs (bp) spanning the
      E4 and L2 genes of the EPV genome and consensus PV primers that amplified a 102
      bp region of the L1 gene. Group-specific PV structural antigens were detected
      with the use of a streptavidin-biotin-alkaline phosphatase IHC stain. With IHC
      testing, 23 of 38 papillomas, 4 of 9 aural plaques, and 0 of 10 sarcoids were
      positive for PV antigen; EPV DNA was found in 20 of the 38 papillomas and 1 of
      the 10 sarcoids but 0 of the 9 aural plaques. The consensus primers did not
      amplify novel PV DNA in any of the tissues. Nucleotide sequencing of viral DNA
      from 7 papillomas amplified with EPV-specific primers revealed DNA fragments that
      were 96% to 99% identical to known EPV sequences. Some samples had nucleotide
      substitutions in common, which suggests infection with related strains. Together,
      EPV DNA or PV antigen (or both) was demonstrated in 26 (68%) of the 38 equine
      papillomas. Although aural plaques contained PV antigen, they were negative for
      EPV DNA; therefore, we hypothesize that aural plaques contain a PV distinct from
      EPV.

PMID- 17193881
TI  - Effects of acepromazine on the stress response in Southern chamois (Rupicapra
      pyrenaica) captured by means of drive-nets.
AB  - This study was conducted to assess the stress response of Southern chamois
      (Rupicapra pyrenaica) to capture and physical restraint and the effects of
      acepromazine (a short-acting neuroleptic) on this response. Forty free-ranging
      Southern chamois were captured, injected intramuscularly with acepromazine (19
      animals, randomly selected) or saline (the other 21 animals), and physically
      restrained for 3 h. Heart rate and body temperature were monitored with
      telemetric devices, and blood samples were obtained at capture and every hour
      thereafter to determine hematologic and serum biochemical parameters. The lower
      heart-rate variability, temperature, erythrocyte count, hemoglobin concentration,
      packed cell volume (PCV), and serum creatine kinase activity in the animals
      treated with acepromazine indicated that this agent reduced the adverse effects
      of stress. According to the differences in heart rate, erythrocyte count,
      hemoglobin concentration, PCV, lymphocyte count, and serum concentrations of
      glucose, creatinine, chloride, and potassium, alpha-adrenergic stimulation by
      catecholamines seemed to be stronger in females, whereas the adrenal-cortex
      reaction seemed to be stronger in males. The differences in erythrocyte
      parameters, temperature, serum creatine kinase activity, and serum concentrations
      of potassium and chloride indicated that acepromazine's beneficial effects were
      greater in females.

PMID- 17193882
TI  - Effects of nitric oxide on bovine polymorphonuclear functions.
AB  - The effects of nitric oxide (NO) on the functionality of polymorphonuclear
      neutrophils (PMNs) in bovine milk or blood were investigated. In 2 experiments,
      mastitis was induced by infusing both hind quarters with saline containing
      Escherichia coli endotoxins. In addition, the left hind quarter was infused with
      aminoguanidine, an inhibitor of the inducible form of NO synthase (iNOS). At
      various times after infusion, somatic cells were isolated from milk samples, and
      superoxide (O2-) production induced by phorbol myristate acetate was evaluated.
      In both experiments, the addition of aminoguanidine had no inhibitory effect on
      the number of milk somatic cells or on their O2- production. The effect of NO and
      iNOS inhibitors on the functionality of bovine PMNs isolated from blood was
      investigated in vitro. The neutrophils did not produce NO. A neutrophil:monocyte
      co-culture system was used to study the effect of NO derived from monocytes on O2
      production by bovine neutrophils. Neither NO derived from activated monocytes
      nor the iNOS inhibitors aminoguanidine and L-N6-(1-iminoethyl)lysine had an
      effect on the ability of bovine neutrophils to release O2-. Moreover,
      aminoguanidine did not affect the ability of bovine neutrophils to phagocytose
      bacteria. These results suggest that inhibition of NO release during inflammation
      does not interfere with the migration of immune cells to the site of infection or
      the ability of these cells to destroy pathogens. Thus, NO does not appear to play
      a major role in the control of the functions of bovine neutrophils.

PMID- 17193883
TI  - Effects of feeding sunflower oil or seal blubber oil to horses with recurrent
      airway obstruction.
AB  - A crossover feeding trial was performed with 9 horses suffering from recurrent
      airway obstruction (RAO). The study aimed to determine whether ingestion of
      sunflower oil (SFO), rich in linoleic acid, or seal blubber oil (SBO), a source
      of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs), changes the
      fatty acid (FA) ratios in plasma and leukocyte membrane phospholipids (PLs) or
      the leukocyte numbers or proportions of cell types in the airways. We also
      investigated diet-related changes in respiratory rate, maximum change in pleural
      pressure (deltaPpl(max)), dynamic compliance (C(dyn)), and pulmonary resistance
      (RL). Each animal was fed hay and oats supplemented with 320 mg/kg body weight
      (BW) of either SFO or SBO for 10 wk. Before and after the feeding periods, we
      performed FA analyses, cytologic testing of the pulmonary epithelial lining fluid
      (PELF), clinical scoring, and pulmonary function testing. The results
      demonstrated that supplementary FAs were readily ingested and incorporated into
      leukocyte cell membranes. The n-6:n-3 FA ratios in plasma and leukocyte PLs were
      reduced after SBO supplementation, as were the PELF leukocyte counts (P < 0.05).
      On the other hand, pulmonary function and clinical signs were not markedly
      changed by the different dietary FAs. These results indicate a possible influence
      of dietary n-3 PUFAs on the pulmonary inflammation of horses with RAO. Further
      studies are warranted to address effects on inflammatory mediators and clinical
      outcome.

PMID- 17193884
TI  - Terbutaline pharmacokinetics in cows: preliminary data.
AB  - The objective of this study was to determine the serum pharmacokinetics of
      terbutaline in healthy cows. In the initial experiment, terbutaline was
      administered once as an intravenous (i.v.) bolus to 6 near-term pregnant beef
      cows within 24 h after parturition at a low but therapeutically relevant dose, 5
      microg/kg. A 2nd experiment was conducted in the same cows with a higher dose,
      0.5 mg/kg, but an otherwise similar experimental design. The serum concentration
      of terbutaline was determined by means of high-performance liquid chromatography
      with fluorescence detection in both experiments. After i.v. administration of 0.5
      mg/kg, the mean peak serum concentration, residence time, and half-life were
      708.22 (standard deviation 509.6) ng/mL, 6.75 (3.6) min, and 6.93 (2.4) min,
      respectively. The results indicate that terbutaline is rapidly eliminated from
      the bloodstream after i.v. administration in cattle, falling below the assay's
      limit of detection 30 min after administration.

PMID- 17193885
TI  - Pharmacokinetics and milk penetration of ibafloxacin after intravenous
      administration to lactating goats.
AB  - The pharmacokinetic behavior of ibafloxacin was studied after intravenous
      administration of a single dose of 15 mg/kg to 6 healthy lactating goats. Plasma
      concentrations of ibafloxacin were determined by high-performance liquid
      chromatography with fluorescence detection. The data for concentration versus
      time could best be described by a 2-compartment model. The mean plasma
      ibafloxacin clearance (and standard error) was 1.05 (0.10) L/h x kg. The mean
      steady-state volume of distribution was 1.65 (0.42) L/kg. The mean elimination
      half-life was 3.76 (0.30) h. Ibafloxacin penetration from the blood to the milk
      was poor. The ratio between the areas under the concentration-time curve of milk
      and plasma was 0.20 (0.01), indicating scant penetration of ibafloxacin into the
      milk.

PMID- 17193886
TI  - Anticipated 2007 nursing legislation in Colorado.

PMID- 17193887
TI  - New program aims to "LIFT" numbers of nursing teachers, ease nursing shortage.

PMID- 17193888
TI  - Color-coded wristband standardization in Colorado.

PMID- 17193889
TI  - Nursing formation in Kyrgyzstan.

PMID- 17193890
TI  - Evolution of medical application of syringe.

PMID- 17193891
TI  - Meditation and mental well being.

PMID- 17193893
TI  - Evaluation of memory in abacus learners.
AB  - Abacus is a method used by Chinese, Japanese and Koreans to improve mathematical
      skills. This system has now invaded our country. The improvement in mathematical
      skills is said to be due to a coordinated functioning of both right and left
      hemisphere. As learning and memory in any field is achieved by coordinating and
      analyzing the different sensory inputs, whether an abacus trainee would also
      improve the short-term memory as a whole was evaluated in our study. 50 children
      of average IQ between 5 and 12 years from 2 regular schools and 50 from an abacus
      institute were evaluated for short-term memory before and after a period of one
      and two years. The memory tests were taken from Wechsler memory scale, Mini
      mental state examination, Mann - Buitar visual memory screen for objects. The
      results showed that the abacus learners at the end of one and two years had a
      better visual and auditory memory when compared to non-abacus learners.

PMID- 17193892
TI  - Effect of exogenous selenium on the testicular toxicity induced by ethanol in
      rats.
AB  - The effects of supplementation of selenium at a dose of 10 microg/ kg body weight
      were investigated on ethanol induced testicular toxicity in rats. In the present
      study, four groups of male albino rats were maintained for 60 days, as follows:
      (1) Control group (normal diet) (2) Ethanol group (4g/kg body weight) (3)
      Selenium (10 microg/kg body weight) (4) Ethanol + Selenium (4g/kg body weight +
      10 microg/kg body weight). Results revealed that ethanol intake caused drastic
      changes in the sperm count, sperm motility and sperm morphology. It also reduced
      the levels of testosterone and fructose. The activities of 3betaHSD, 17betaHSD in
      the testis and SDH in the seminal plasma were also reduced. Lipid peroxidation
      was also enhanced as the lipid peroxidation products were increased and the
      activities of the scavenging enzymes were reduced. But on coadministration of
      selenium along with alcohol all the biochemical parameters were altered to near
      normal levels indicating a protective effect of selenium. These results were
      reinforced by the histopathological studies.

PMID- 17193894
TI  - New method of electrode placement for determination of cardiac output using
      impedance cardiography.
AB  - In thirty eight young healthy adult subjects, cardiac output was determined non
      invasively by using two methods of electrode placement viz. vertical (uses silver
      braided wires in a band shape) and horizontal (conventional stick-on type surface
      ECG electrodes), using the technique of Impedance Cardiography. The recordings
      were taken in supine position on the same day in two separate sets with 30.0 min
      interval between two sets. In each set of recording, five successive recordings,
      each at an interval of five minutes were taken. The mean values of cardiac out
      put by two methods were compared. For the set I, the respective values (Mean +/-
      SD) of cardiac output by horizontal and vertical methods for the each of the five
      recordings were 4.87 +/- 0.77 and 5.03 +/- 0.64 for the first, 4.87 +/- 0.71 and
      4.91 +/- 0.66 for the second, 4.99 +/- 0.67 and 5.00 +/- 0.70 for the third, 4.78
      +/- 0.69 and 4.98 +/- 0.61 for the fourth, 4.84 +/- 0.69 and 4.98 +/- 0.62 for
      the fifth recording in supine position. The respective P values for these pairs
      for between the group comparisons were 0.33, 0.50, 0.96, 0.17, and 0.36. In
      addition, to see the repeatability for each method, within the group comparison
      was done, the P values were 0.71 and 0.91 for the horizontal and vertical
      methods, respectively. The mean value of cardiac output did not differ
      significantly between two methods for recordings of set II in supine position.
      The cardiac output measurement by placing four spot electrodes horizontally, gave
      consistent result on repeated measurements and their values showed concordance
      with the cardiac output values obtained by conventional four band electrodes tied
      around the chest.

PMID- 17193895
TI  - Effect of aqueous extract of neem (Azadirachta indica) leaves on offensive and
      diffensive gastric mucosal factors in rats.
AB  - Standardized aqueous extract of Neem (Azadirachta indica) leaves (AIE) has been
      reported to show both ulcer protective and ulcer healing effects in normal as
      well as in diabetic rats. To study the mechanism of its ulcer protective/healing
      actions, effects of AIE (500 mg/ kg) was studied on various parameters of
      offensive acid-pepsin secretion in 4 hr pylorus ligation, pentagastrin (PENTA, 5
      microg/kg/hr)-stimulated acid secretion and gastric mucosal proton pump activity
      and defensive mucin secretion including life span of gastric mucosal cells in
      rats. AIE was found to inhibit acid-pepsin secretion in 4 hr pylorus ligated
      rats. Continuous infusion of PENTA significantly increased the acid secretion
      after 30 to 180 min or in the total 3 hr acid secretion in rat stomach perfusate
      while, AIE pretreatment significantly decreased them. AIE inhibited the rat
      gastric mucosal proton pump activity and the effect was comparable with that of
      omeprazole (OMZ). Further, AIE did not show any effect on mucin secretion though
      it enhanced life span of mucosal cells as evidenced by a decrease in cell
      shedding in the gastric juice. Thus, our present data suggest that the ulcer
      protective activity of AIE may be due to its anti-secretary and proton pump
      inhibitory activity rather than on defensive mucin secretion. Further, acute as
      well as sub acute toxicity studies have indicated no mortality with 2.5 g/kg dose
      of AIE in mice and no significant alterations in body or tissues weight, food and
      water intake, haematological profile and various liver and kidney function tests
      in rats when treated for 28 days with 1 g/kg dose of AIE.

PMID- 17193896
TI  - Effect of simulated ascent to 3500 meter on neuro-endocrine functions.
AB  - Ascent to extreme High Altitude (HA) is in steps and it entails acclimatization
      at moderately HA locations. In terms of acclimatization, it is pertinent to
      understand the physiological changes, which occur on immediate ascent to moderate
      HA. The study aimed to evaluate the effect of ascent to 3500 m on neuro-endocrine
      responses in the first hour of induction. The plasma levels of catecholamines and
      cortisol were measured before and after one hour of ascent to high altitude. The
      peripheral oxygen saturation (SpO2), Galvanic Skin Resistance (GSR), Heart Rate
      (HR) and Blood Pressure (BP) were simultaneously monitored. The plasma
      epinephrine, norepinephrine, dopamine and cortisol were increased after one-hour
      exposure to 3500 m altitude as compared to before exposure. The SpO2 showed a
      significant decrease during and after high altitude induction. The heart rate and
      diastolic BP increased at 3500 m whereas the GSR did not show significant
      changes. There are changes in neuroendocrine responses, which reflect a
      sympathetic over activity in the first hour of exposure to 3500 m.

PMID- 17193897
TI  - A study of stress and autonomic nervous function in first year undergraduate
      medical students.
AB  - Psychological stress is a risk factor for hypertension and coronary artery
      disease. The purpose of this study was to assess the impact of real life
      stressor, that of stress among first year medical students on cardiac autonomic
      regulation. Stress levels in 36 non-smoking, healthy first year medical students
      of either gender were assessed on a self-rating scale. Cardiac autonomic
      regulation was tested using both conventional tests and spectral analysis of
      heart rate variability (HRV). Nine subjects who obtained scores on the stress
      scale in the upper quartile were classified as the "stress" group and the rest
      constituted the "no stress" group (n = 27). There were no significant differences
      between the two groups on any of the conventional tests of autonomic nervous
      activity. The low frequency power in normalized units and low frequency high
      frequency ratio of heart rate variability in supine posture was significantly
      higher in the "stress" group compared to the "no stress" group. The low frequency
      power in normalized units was significantly positively correlated with total
      stress score. The changes were suggestive of a tilt in the resting cardiac
      autonomic balance towards increased sympathetic activity.

PMID- 17193898
TI  - Anti-seizure efficacy of nimodipine in pentylenetetrazole and kainic acid
      combined seizure models in mice.
AB  - The present study aimed at establishing two models of experimental seizures by
      combination treatment with subconvulsive doses of PTZ and kainic acid in adult
      male mice and evaluating the modulatory role of cerebroselective dihydropyridine
      calcium channel blocker, nimodipine. The CD50 +/- SEM value for PTZ was found to
      be 20.00 +/- 0.92 mg/kg, ip in kainic acid (administered at per se subconvulsive
      dose of 1.00 mg/kg, ip) pretreated mice while CD50 +/- SEM value for kainic acid
      was found to be 0.30 +/- 0.08 mg/kg, ip in PTZ (administered at per se
      subconvulsive dose of 30.00 mg/kg, ip) pretreated mice. Nimodipine (5.00 mg/kg,
      ip) significantly protected the mice from seizure in both of the combination in
      vivo seizure models. The results suggested synergistic interaction between PTZ
      and kainic acid at subconvulsive dose combination while the protective efficacy
      of nimodipine suggested the role of calcium ion as an important mediator for the
      genesis of seizures.

PMID- 17193899
TI  - Effect of smoking on lipid profile and lipid peroxidation in normal subjects.
AB  - The aim of the present study was to assess the association between smoking and
      the alteration in plasma concentration of lipid profile and lipid peroxides.
      Fourteen smokers and 11 age matched control were enrolled. Plasma levels of
      fasting cholesterol, triglycerides, lipoprotein cholesterol and malondialdehyde
      were estimated. In smokers the levels of total cholesterol, LDL cholesterol, Non
      HDL cholesterol and MDA were significantly elevated when compared with the
      controls. The atherogenic index as indicated by various risk ratios were also
      found to be increased in smokers as compared to controls. These findings indicate
      that current smokers are at a pro- atherogenic state and as in other countries,
      in India smokers require particular attention in terms of public health
      interventions.

PMID- 17193900
TI  - An evaluation of thyroid hormone status and oxidative stress in undialyzed
      chronic renal failure patients.
AB  - Chronic renal failure (CRF) patients on prolonged dialysis have been found to
      have significant alteration in their thyroid status, but little is known about
      the same in undialyzed CRF patients. Oxidative stress has been implicated as the
      key player in altering the levels of thyroid hormone in euthyroid sick syndrome.
      This study was performed to evaluate the levels of oxidative stress and thyroid
      status in undialyzed CRF patients. A case control study was performed on 20
      undialyzed CRF patients and 20 control subjects. There was a significant decrease
      in the levels of T3, T4, total protein and albumin levels in CRF patients when
      compared to control. There was a significant increase in the level of
      malondialdehyde and total antioxidant status in CRF patients when compared with
      control subjects. The present study confirms oxidative stress along with altered
      thyroid status in CRF patients.

PMID- 17193901
TI  - "Effect of short-term cigarette smoking on insulin resistance and lipid profile
      in asymptomatic adults".
AB  - Present study examined the effect of short-term cigarette smoking on insulin
      resistance and lipid profile in asymptomatic healthy adults. This case control
      study comprised of 44 healthy male subjects in the age group of 18-40 yrs having
      BMI 25+3 and WHR < 1.0. Of these 22 smokers were included in the study group and
      22 non-smokers in the control group. Subject selection was done such that one
      smoker and one non-smoker sibling or first degree male relative were selected
      from the same family. We compared fasting plasma glucose, insulin, lipid profile,
      and homeostatic model assessment index (HOMA Index) as a measure of insulin
      resistance between both the groups. Our observation showed that significantly
      higher values of serum glucose (133.36 +/- 23.45 mg/dl; P < 0.001), serum insulin
      (32.04 +/- 6.0 2 microU/ml; P < 0.001) and HOMA index (3.62 +/- 0.21; P < 0.001)
      were found in smokers as compared to non-smokers (serum glucose 86.95 +/- 19.32
      mg/dl, insulin 20.09 +/- 4.8 microU/ml, HOMA index 3.29 +/- 0.30). No significant
      difference was observed for number of subjects having insulin resistance (HI >
      3.8) and lipid profile in both the groups. Thus it appears that smokers are prone
      to develop hyperinsulenemia, hyperglycemia and the metabolic syndrome.

PMID- 17193902
TI  - Alcohol abuse-duration dependent decrease in plasma testosterone and antioxidants
      in males.
AB  - Ethanol is a testicular toxin and it causes fertility abnormalities with low
      sperm count and impaired sperm motility in men. The present study was designed to
      investigate plasma testosterone level and hypothalamic pituitary gonadal (HPG)
      axis function in alcoholic men and also effect of ethanol on systemic oxidative
      stress. Forty six male alcohol abusers in the age group 20-40 years were
      selected. Fifty five, males in the same age group served as control. Alcohol
      abusers had significantly low plasma testosterone with low luteinizing hormone
      and follicle stimulating hormone. In addition they had significantly high
      thiobarbituric acid reactive substances (TBARS), superoxide dismutase and
      glutathione S-transferase, and low glutathione, ascorbic acid, catalase,
      glutathione reductase and glutathione peroxidase. Moreover, serum testosterone
      level in alcoholics negatively correlated with duration of alcohol abuse, and
      TBARS. Duration dependent decreased serum testosterone level in alcohol abusers
      might be due to 1) increased oxidative stress which can damage Leydig and
      supporting Sertoli cells and 2) impaired HPG axis.

PMID- 17193903
TI  - Antioxidant activity of Albizzia lebbeck (Linn.) Benth. in alloxan diabetic rats.
AB  - There is an increasing demand for natural anti-diabetic drugs, as continuous oral
      administration of insulin can culminate in many side effects and toxicity. In our
      endeavour to formulate some cost-effective herbal medicines for diabetes, we
      undertook this study to evaluate the antioxidant potential of aqueous extract of
      Albizzia lebbeck (ALL) in diabetic rats. The oxidative stress in alloxan-induced
      diabetic rats was determined by estimating the levels of thiobarbituric acid
      reactive substances (TBARS), conjugated dienes (CD) and reduced glutathione (GSH)
      in liver and kidneys. Activities of antioxidant enzymes, such as superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione S
      transferase (GST) were assessed in diabetic as well as rats co-administered with
      ALL. Oxidative damage in the liver and kidneys of diabetic rats as evidenced by a
      marked increment in the levels of TBARS and CD, and also a distinct diminution in
      GSH content was nullified by ALL, as these parameters showed a tendency to
      retrieve towards normalcy on co-administration of the herbal drug. The
      antioxidant enzymes registered a decline in activity in diabetic rats thus
      revealing the damaging effects of free radicals generated due to alloxan
      exposure. The activities of these enzymes returned to normalcy in ALL
      administered rats indicating the antioxidant efficacy of the drug in resisting
      oxidative insult. The findings provide a rationale for further studies on
      isolation of active principles and pharmacological evaluation.

PMID- 17193904
TI  - Base excess significantly corrected for the variations in apparent dissociation
      constant for human blood gas testing.
AB  - We introduce a pragmatic approach towards the corrected Base Excess (BE) by
      including the large variability of the apparent dissociation constant pK' in non
      logarithmic form in Henderson-Hasselbach bicarbonate ion equilibria thereby
      resulting in a significant correction both in calculated bicarbonate ion
      concentration and BE at 37 degrees C.

PMID- 17193905
TI  - Intrastrain variations in anxiolytic effect of nitrazepam in mice.
AB  - This study investigated the individual differences in the baseline anxiety and
      anxiolytic effect of nitrazepam in Balb/c mice. Initially mice were sorted
      according into low, intermediate and high anxiety groups (LA, IA and HA) based on
      the number of entries to and time spent in open arms in elevated plus maze.
      Later, anxiolytic effect of nitrazepam (2 mg/kg, p.o) in LA, IA and HA mice was
      evaluated using hole board and light/dark tests. In Hole board test, LA mice made
      more number of head dippings and spent more time during head dippings, while HA
      mice made less number of head dippings and spent less time during head dipping
      when compared to that of IA mice. In light/dark test LA mice made more reentries
      to and spent more time in bright compartment, while HA mice made few reentries to
      and spent less time in bright compartment. Results suggest that mice of a single
      strain differ in their baseline anxiety and anxiolytic effect of nitrazepam.

PMID- 17193906
TI  - Pulmonary function tests in saw mill factory workers.

PMID- 17193907
TI  - Gender differences in vasoconstrictor reserve.

PMID- 17193909
TI  - Emergency practice.

PMID- 17193908
TI  - A study of fatiguing isometric contractions of the human first dorsal
      interosseous muscle.

PMID- 17193910
TI  - Now and then. Paediatric nursing seen through the season of Christmas.

PMID- 17193911
TI  - Supplementary prescribing case study.
AB  - A principle aim of supplementary prescribing is to enable faster access to
      medicines for people who have a chronic condition. The example of a young person
      with diabetes is used to demonstrate the benefits of nurse specialists being able
      to prescribe. The way in which prescribing requirements, such as clinical
      management plans, relate to existing multi-disciplinary team management of
      children with chronic illness is also illustrated. Having the young person and
      family as partners within the team is essential; use of management plans
      reinforces this partnership and allows care to be delivered in a structured way.

PMID- 17193912
TI  - Blood transfusion practice.

PMID- 17193913
TI  - Evaluating a self infusion device for children with haemophilia.
AB  - Although prophylactic treatment of boys with severe haemophilia has progressed
      significantly, there has been very little change in the way that coagulation
      factors are reconstituted and administered. Most boys with severe haemophilia can
      self infuse by the age of eight and most are totally self sufficient by the age
      of 14. This small study evaluated a product developed to improve the
      reconstitution and administration process by seeking the views of ten boys who
      self infuse recombinant coagulation factor. The boys completed a simple
      questionnaire related to the current method and after the introduction of new
      method of reconstitution using the ReFacto Rapid Reconstitution (R2) device. The
      R2 device was reported by most boys to be advantageous in terms of time and
      safety in reconstitution as well as being acceptable to all but one. Even
      relatively young children can be successfully included in research and their
      opinions about their health care should be sought before introduction of changes,
      especially when proposed changes could affect their ability to perform their own
      treatment.

PMID- 17193914
TI  - Ophthalmology: spreading the word on compliance.

PMID- 17193915
TI  - Spiritual care for sick children of five world faiths.
AB  - The holistic care of those with a specific religious faith and those with a
      spiritual belief is important for good family-centred care. Within a busy
      clinical setting an important aspect of spiritual care is enabling participation
      in religious observance, where desired. Children's nurses, midwives and hospital
      chaplains are instrumental in striving to ensure that both a suitable environment
      and appropriate spiritual support are offered. According to data from the 2001
      census for England, Wales and Scotland, the most common religious affiliations
      after Christianity are Muslim, Hindu, Sikh, Jewish and Buddhist. This article
      considers the rites, rituals or ceremonies for each of these religions which are
      deemed both necessary and helpful after birth or when a child is sick or dying.

PMID- 17193916
TI  - Cervical cancer prevention: vaccine for girls.

PMID- 17193917
TI  - Preparation of children for spinal surgery: an exploratory study.
AB  - AIM: The United Kingdom (UK) Scoliosis Association (2001) estimate that three in
      every 1,000 adolescents with scoliosis require hospital treatment amounting to at
      least 1,000 patients per year undergoing surgery. This exploratory study
      identified qualified nurses' feelings towards preparing children and young people
      and their families for spinal surgery. METHOD: In-depth interviews, observation
      of practice and a questionnaire survey were carried out with nine qualified
      nurses. Themes were then developed to inform the development of a questionnaire
      constructed of statements requiring Likert style responses. The questionnaire was
      distributed to 30 qualified nurses from hospital and community settings who cared
      for children and young people requiring spinal surgery. Responses were received
      from 23 nurses and these were analysed using descriptive statistics. The findings
      reported here relate to this survey questionnaire. RESULTS: The findings
      highlighted the importance and influence of communication skills but opinions
      differed regarding the effect that poor communication could have on the surgical
      care of these children. There was no consensus about which tools were deemed most
      suitable for use in preparing children for spinal surgery. Conflicting
      information was seen as detrimental. Training and education for professionals
      were viewed as important and positive measures that may need improvement.
      CONCLUSIONS: Nurses working with children, young people and their families are
      aware that they have a vital role to play in the preparation of children and
      young people for spinal surgery in both hospital and community settings. This
      small study suggested the need for: improved multi-disciplinary education on the
      subject of spinal surgery; development of a national care pathway to underpin
      consistent care and audit; and more specific information resources for children,
      young people and families.

PMID- 17193918
TI  - Chronic pain in children and adolescents.
AB  - Chronic pain is a widespread and significant clinical problem. It can result in
      major negative short- and long-term physical and emotional effects in multiple
      domains of children's and their families' lives as Pain Associated Disability
      Syndrome. Assessment of chronic pain is challenging but it is an essential
      clinical task. Management requires a multidimensional response focussing on the
      whole patient. Specialist pain management units and programmes use cognitive
      behavioural methods and promote adaptive coping and focus on the child re
      engaging with normal activities. While chronic pain is not well understood, there
      is emerging evidence that young people and their parents can recover from chronic
      disability, dependency and distress, and return to a normal life.

PMID- 17193919
TI  - Pre-registration children's and young people's nurse preparation. A SWOT
      analysis.
AB  - An investigation was undertaken into the views of nurse educators on current
      approaches to preparing children's and young people's nurses in the UK. A
      convenience sample of lead academics in 17 child health nursing departments of
      British universities was contacted by email and invited to liaise with colleagues
      to generate lists of the strengths, weaknesses, opportunities and threats (SWOT)
      of the educational system. Thirteen departments provided data that were analysed
      and themed. Major themes included the common foundation programme, clinical
      skills learning, clinical placements and employment. More detailed evaluative
      work should be undertaken before wholesale changes are made to a relatively new
      curriculum.

PMID- 17193920
TI  - An introduction to Turner syndrome.
AB  - Turner syndrome is a chromosomal condition affecting around 1 in 2,000 girls born
      in the UK. The severity of the problems experienced can be partly predicted by
      the child's karyotype but some are mediated by the social and other life
      experiences of the developing child. Management focuses on minimising the effects
      of the condition on the girls' lives and promoting their long term health and
      wellbeing. Nurses specialising in paediatric endocrinology have a valuable role
      in supporting the child and family and in educating families and colleagues with
      regard to the medical, psychosocial and educational needs of these children.

PMID- 17193921
TI  - Identification and characterization of DEDDL, a human-specific isoform of DEDD.
AB  - Death effector domain (DED) containing molecules are usually involved in the
      intracellular apoptosis cascade as executioners or regulators. One of these
      molecules, DEDD, was identified as a final target of the CD95 signaling pathway
      by which it would be transferred into the nucleolus to inhibit RNA polymerase I
      dependent transcription. Here we describe a longer isoform of DEDD, DEDDL,
      produced by alternatively splicing, as an immune cell-specific DED-containing
      molecule. It is only expressed in human T lymphocytes and dendritic cells (DCs),
      and the mRNA expression in DCs was elevated upon inductive maturation. In cell
      lines MCF-7 and Jurkat, the overexpression of DEDDL could induce apoptosis more
      potently than that of DEDD. That DEDDL could bind FADD and cFLIP more potently
      than DEDD in vivo was revealed by cotransfection and immunoprecipitation. This
      may explain why DEDDL is a more potent apoptosis inducer, because DED-containing
      proteins usually induce apoptosis through DED binding. Finally, why DEDD and
      DEDDL are unstable in the overexpression and other studies may be explained by
      the finding that they are potential substrates of active caspases.

PMID- 17193922
TI  - Growth arrest-inducing genes are activated in Dbl-transformed mouse fibroblasts.
AB  - The Dbl oncogene is a guanine nucleotide exchange factor for Rho GTPases and its
      activity has been linked to the regulation of gene transcription. Dbl oncogene
      expression in NIH3T3 cells leads to changes in morphological and proliferative
      properties of these cells, inducing a highly transformed phenotype. To gain
      insights into Dbl oncogene-induced transformation we compared gene expression
      profiles between Dbl oncogene-transformed and parental NIH3T3 cells by cDNA
      microarray. We found that Dbl oncogene expression is associated with gene
      expression modulation involving upregulation of 51 genes and downregulation of 49
      genes. Five of the overexpressed genes identified are known to exert
      antiproliferative functions. Our observations suggest that the expression of Dbl
      oncogene in NIH3T3 may lead to the induction of genes associated with cell cycle
      arrest, possibly through the activation of stress-induced kinases.

PMID- 17193923
TI  - Posttranscriptional control is a strong factor enabling exclusive expression of
      surface antigens in Paramecium tetraurelia.
AB  - Variable antigens are large proteins located on the outer membrane of parasitic
      but also of free-living protists. Multigene families encoding surface antigens
      demonstrate an exclusive expression of proteins. The resulting presence of just
      one protein species on the cell surface is required for surface antigen function;
      therefore, the molecular mechanism of exclusive expression is of main interest.
      Regulation of gene expression and mechanisms establishing switching of antigens
      are hardly understood in any organism. Here we report on the reaction of
      Paramecium to the artificial knock down of surface antigen 51A expression by
      bacteria-mediated RNAi. This technique involves the feeding of dsRNA-producing
      bacteria. We analyzed different fragments of the target gene for dsRNA template
      regarding their specific knock down efficiency and found great differences.
      Treatment of Paramecia with RNAi against the 51A antigen demonstrated that
      although a massive amount of mRNA was present, the protein was not detected on
      the cell surface. Moreover, a minor abundance of 51D transcripts resulted in an
      exclusive presence of 51D proteins on the cell surface. This posttranscriptional
      regulation was confirmed by the transcript ratio (51A/51D) determined by real
      time (RT) PCR of single cells. Because we were able to document unexclusive
      transcription also in wild-type cells our results indicate that this
      posttranscriptional regulation is a main factor of enabling exclusive gene
      expression. The comparison of serotype shifts, caused by efficient and
      inefficient knock down, indicates an involvement of full-length transcripts in
      regulation of gene expression. Thus, our study gives new insights into the
      mechanism of exclusive expression on the molecular level: (i) exclusive
      transcription does not occur, (ii) posttranscriptional regulation is a powerful
      factor enabling exclusive antigen expression, and (iii) surface antigen mRNA is
      shown to be involved in this mechanism in a regulating way.

PMID- 17193924
TI  - An efficient strategy to identify early TPA-responsive genes during
      differentiation of HL-60 cells.
AB  - We have adopted a special experimental strategy to identify early responsive
      genes during 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced macrophage-like
      differentiation of human myeloid leukemia cells (HL-60). This was performed in
      cells that were synchronized by nocodazole and treated with TPA in the presence
      of a protein synthesis inhibitor, cycloheximide, to prevent activation of
      secondary targets and therefore increase the probability of early transcripts in
      total RNA pool. The expression alteration was analyzed by microarray and the
      selection criteria of candidate genes were adjusted by real-time PCR validation
      to increase its reliability. Finally, 56 genes were identified as early TPA
      responsive genes in this multiscreening step approach. Furthermore, upregulation
      of three candidate genes (NFIL3, SKIL, and JMJD3) was shown to be dosage and time
      dependent with TPA treatment and was found to be directly regulated by TPA
      through PKC-dependent signaling. These results revealed that our screenings
      provide a useful and efficient approach to identify early TPA-responsive genes
      and these genes might involve the regulation of TPA-induced differentiation
      program of HL-60 cells as primary

PMID- 17193925
TI  - Gene expression profile of B 16(F10) murine melanoma cells exposed to hypoxic
      conditions in vitro.
AB  - Hypoxia is an important feature of tumor microenvironment, exerting far-reaching
      effects on cells and contributing to cancer progression. Previous studies have
      established substantial differences in hypoxia response between various cell
      lines. Investigating this phenomenon in melanoma cells contributes to a better
      understanding of cell lineage-specific hypoxia response and could point out novel
      hypoxia-regulated genes. We investigated transcriptional activity of B 16(F10)
      murine melanoma cells cultured for 24 h under hypoxic (nominal 1% O2, 15 samples
      including controls) and hypoxia-mimicking conditions (cobalt chloride, 100 or 200
      microM, 6 samples including controls). Gene expression profiles were analyzed
      using MG-U74Av2 oligonucleotide microarrays. Data analysis revealed 2541
      probesets (FDR <5%) for 1% oxygen experiment and 364 probesets (FDR <5%) for
      cobalt chloride, which showed differences in expression levels. Analysis of
      hypoxia-regulated genes (true hypoxia, 1% O2) by stringent Family-Wise Error Rate
      estimation indicated 454 significantly changed transcripts (p < 0.05). The most
      upregulated genes were Lgals3, Selenbpl, Nppb (more than ten-fold increase). We
      observed significant differences in expression levels of genes regulating
      glycolysis (Pfkp, Hk2, Aldo3, Eno2), apoptosis (Bnip3, Bnip31, Cdknla),
      transcription (Bhlhb2, Sap30, Atf3, Mxil), angiogenesis (Vegfa, Adm, Anxa2,
      Ctgf), adhesion (Pkp2, Itga4, Mcam), migration (Cnn2, Tmsb4x), and other
      processes. Both true hypoxia and hypoxia mimicry induced HIF-1-regulated genes.
      However, unsupervised analysis (Singular Value Decomposition) revealed distinct
      differences in gene expression between these two experimental conditions.
      Contrary to hypoxia, cobalt chloride caused suppression of gene expression rather
      than stimulation, especially concerning transcripts related to proliferation,
      immune response, DNA repair, and melanin biosynthesis.

PMID- 17193927
TI  - Icons and heros: Philip J. Boyne, DMD, MS, DSc (H.C).

PMID- 17193928
TI  - Dimensional accuracy of a binder jet model produced from computerized tomography
      data for dental implants.
AB  - A full-scale model produced by multislice helical computerized tomography (CT)
      was made by using the binder jet method and applied for presurgical diagnosis,
      surgical simulation, and the production of surgical templates for dental implant
      treatment. In this study, accuracy of the full-scale model with plaster powder
      was assessed by shifting the binary threshold values. A step phantom was made
      from bone-equivalent material. When it was placed in water, the CT imaging was
      performed with a multislice helical CT unit. Three-dimensional (3-D) images were
      reconstructed by 3-D visualization software. Using 4 different threshold values,
      full-scale models were produced by a binder jet method with plaster powder. All
      sides of the full-scale models were directly measured, and their values were
      compared with that of the step phantom. The mean difference was approximately 0.1
      mm in the axial plane when the setting was 0.75 for the threshold. In total, the
      mean difference was approximately 0.2 mm when the setting was 0.50 for the
      threshold. It is suggested this full-scale model could be applied for presurgical
      diagnosis, surgical simulation, and the production of surgical templates in
      dental implant treatment.

PMID- 17193926
TI  - Multiregional gene expression profiling identifies MRPS6 as a possible candidate
      gene for Parkinson's disease.
AB  - Combining large-scale gene expression approaches and bioinformatics may provide
      insights into the molecular variability of biological processes underlying
      neurodegeneration. To identify novel candidate genes and mechanisms, we conducted
      a multiregional gene expression analysis in postmortem brain. Gene arrays were
      performed utilizing Affymetrix HG U133 Plus 2.0 gene chips. Brain specimens from
      21 different brain regions were taken from Parkinson's disease (PD) (n = 22) and
      normal aged (n = 23) brain donors. The rationale for conducting a multiregional
      survey of gene expression changes was based on the assumption that if a gene is
      changed in more than one brain region, it may be a higher probability candidate
      gene compared to genes that are changed in a single region. Although no gene was
      significantly changed in all of the 21 brain regions surveyed, we identified 11
      candidate genes whose pattern of expression was regulated in at least 18 out of
      21 regions. The expression of a gene encoding the mitochondria ribosomal protein
      S6 (MRPS6) had the highest combined mean fold change and topped the list of
      regulated genes. The analysis revealed other genes related to apoptosis, cell
      signaling, and cell cycle that may be of importance to disease pathophysiology.
      High throughput gene expression is an emerging technology for molecular target
      discovery in neurological and psychiatric disorders. The top gene reported here
      is the nuclear encoded MRPS6, a building block of the human mitoribosome of the
      oxidative phosphorylation system (OXPHOS). Impairments in mitochondrial OXPHOS
      have been linked to the pathogenesis of PD.

PMID- 17193929
TI  - Five-year outcome of 111 immediate nonfunctional single restorations.
AB  - Immediate loading is a surgical-prosthetic procedure extensively used in implant
      dentistry. Despite its frequent use, minimal data are available on the long-term
      clinical success rate of immediate functional loading (IFL) and immediate
      nonfunctional loading (INFL) of implants. The aim of this study was to evaluate
      the long-term survival and bone loss of immediate nonfunctional single implant
      restorations in a group of patients that were monitored for 5 years. One hundred
      and eleven patients (41.4% men) with a median age of 40 years were included in
      this study. A total of 111 implants were placed. All implants were placed with a
      minimum insertion torque of 25 Ncm. A temporary restoration was relined with
      acrylic resin, trimmed, polished, and cemented or screw-retained 1 to 2 hours
      later. Occlusal contact was avoided in centric and lateral excursions. After
      provisional crown delivery, a periapical radiograph was performed by means of a
      customized Rinn holder device. Data were analyzed by means of Kaplan-Meier and
      life-table algorithms. Stratification of implant survival was performed for the
      available variables of interest, and comparisons were analyzed using a log-rank
      test. Investigated parameters were time of implant placement, bone quality,
      implant site, implant diameter and length, and type of implant surface
      enhancement. The parameters for overall success rate were defined by bone
      resorption <1.5 mm after the first year of loading and <0.2 mm thereafter. During
      the 5-year follow-up period, a survival rate of 95.5% was observed. All failures
      occurred within 4 months of implant loading. There were statistically significant
      differences regarding healed vs post-extraction implant sites (100% and 92.5%,
      respectively, P = .05) and type of bone (D1 vs D4 yielded 100% and 95.5%,
      respectively, P <.05). No differences were detected for: (1) site (100% for
      mandible and 94.63% for maxilla, P =-.319); (2) implant diameter (survival rates
      of 97.26% for <4.5-mm diameter and 92.11% for >4.5mm diameter, P = .206); (3)
      implant lengths (survival rates of 96.97% for implants >13 mm and 94.87% for
      implants <13 mm, P =.624); and (4) type of implant surface enhancement (survival
      rates of 94.03% for 67 cases of grit-blasted and acid-etched surfaces and a
      failure rate of 4 out of 5, and 94.12% for 17 cases of hydroxyapatite (HA)-coated
      surfaces with only 1 failure). The success rate (defined as bone resorption >1.5
      mm after the first year of loading and >0.2 mm thereafter) was 97.2%. Immediate
      nonocclusal loading of single implants is a reliable surgical-prosthetic
      procedure with a low rate of implant loss and a low quantity of peri-implant bone
      loss over time.

PMID- 17193930
TI  - Restoration of the soft-tissue margin in single-tooth implant in the anterior
      maxilla.
AB  - Esthetic requirements for dental implant restoration have arisen in recent years.
      Despite several surgical techniques that have been developed, the treatment of
      the peri-implant soft-tissue defect is still difficult. The purpose of this
      clinical article is to describe a grafting technique using subepithelial
      connective tissue grafts to recontour soft-tissue margin discrepancy for single
      tooth implant restorations in the anterior maxilla. After 2-year follow-up, this
      procedure shows that the use of connective tissue grafts can be a predictable
      approach to establish new and stable peri-implant soft-tissue margin.

PMID- 17193931
TI  - Telescopic crowns as attachments for implant supported restorations: a case
      series.
AB  - The use of dental implants to support mandibular or maxillary overdentures is a
      widely used treatment modality. Advantages are an increase in retention, an
      increase in chewing ability, and easy access for oral hygiene procedures. While
      telescopic and conical crowns have been used for decades to connect natural teeth
      to overdentures, not many cases have been reported in the literature of
      telescopic crowns placed on implants to support overdentures. This article
      describes 7 patients with overdentures supported by telescopic crowns who
      received 65 implants (ITI Straumann). The cases presented in this report have
      been in function for up to 4.5 years. During that time no adverse events were
      reported. The use of telescopic crowns as attachments for implant-supported
      overdentures may be a viable treatment option.

PMID- 17193932
TI  - Long-term clinical evaluation of tapered multi-threaded implants: results and
      influences of potential risk factors.
AB  - This prospective study evaluated the long-term performance of tapered screw
      implants placed in patients with a variety of potentially compromising clinical
      variables. Sixty patients were treated with 218 implants; each case included one
      or more potential risk factors associated with increased rates of implant
      failure, peri-implant bone loss or clinical complications in the dental
      literature: short implants (23%), comorbid conditions (25%), maxillary implants
      (61%), immediate loading (88.5%), placement into extraction sockets (91%), and
      partial edentulism (97%). The implants were restored with a variety of
      prostheses. Marginal bone changes were calculated utilizing periapical
      radiographs taken at placement and at all subsequent appointments utilizing a
      standardized paralleling device and a 1-mm measurement grid. Mean clinical follow
      up was 67.5 (range: 1-94) months for implants and 60 (range: 15-74) months for
      prostheses. Four implants failed to integrate and were immediately replaced by
      wide-diameter implants. Eight prostheses sustained porcelain fracture (n = 7) or
      cement failure (n = 1) and were replaced. No peri-implant marginal bone loss was
      observed for 98% of the implants; the remaining 2% exhibited 1 mm of bone loss.
      Cumulative survival rates were 98.2% for implants and 96.3% for prostheses after
      5 years of clinical loading. Concerns that tapered implant designs may be more
      prone to crestal bone loss than cylinder designs are unsupported by the results
      of this study. Tapered implants maintained integration and marginal bone levels
      despite the presence of one or more potentially compromising variables.

PMID- 17193933
TI  - Management of retrograde peri-implantitis: a clinical case report.
AB  - The term retrograde peri-implantitis has been commonly used to describe lesions
      in the periapical region of dental implants. There are very few reports on this
      condition, and the exact etiology and pathogenesis are subject to speculation.
      Management of retrograde peri-implantitis is even more scarcely discussed in the
      literature. The current article briefly reviews the literature on this subject
      and presents a case report of retrograde peri-implantitis. Special emphasis is
      placed on the management of the condition, and different strategies are
      critically evaluated. If the fixture is stable despite bone loss in the
      periapical region, it is suggested that surgical debridement be carried out with
      the use of a surface antiseptic like chlorhexidine. Also all possible efforts
      should be made to prevent damage to the implant surface. Bone loss due to this
      condition may be regenerated on the basis of the principle of guided bone
      regeneration.

PMID- 17193934
TI  - Implant placement after marsupialization of a dentigerous cyst.
AB  - This paper presents a case of a dentigerous cyst accompanied by a history of
      inflammation, resorption of the roots of the first molar and the lingual aspect
      of the distal root of the second molar, and devitalization of the 2 premolars.
      The treatment option chosen was marsupialization of the cyst, extraction of the
      involved teeth, endodontic treatment of both premolars, and implant insertion in
      the area of the first mandibular molar at a later stage. Twelve months
      postsurgery the area of interest was almost flattened and the radiographic
      examination revealed total disappearance of the radiolucency. An implant of 15 x
      4 mm was inserted in the area of the first mandibular molar. Despite the
      excellent implant stability achieved, a thin central zone of the defect remained
      void of bone. After complete excision of soft tissue the defect was filled with
      an alloplastic bone substitute. Eight months later (20 months postsurgery), the
      implant was uncovered and the restorative procedure completed. The implant and
      the crown have been functioning sign and symptom free for 48 months.
      Marsupialization was preferred instead of enucleation due to (1) proximity of the
      cyst to the mandibular canal; (2) need for apicectomy of both premolars to gain
      good access for enucleation; (3) refusal of the patient to undergo a second
      surgery for bone harvesting; (4) lower probability for postoperative
      contamination; (5) need of small quantity of bone substitute; (6) easier
      extraction of the impacted second molar due to its coronal movement. The
      disadvantages of the treatment were the long healing period and the discomfort of
      the patient at the early stages of marsupialization. It was judged that the
      advantages outweighed the disadvantages in this case. We discuss the findings of
      other authors who support the conservative approach to jaw cysts in a young
      population, and the concerns that exist in the literature about the ability of
      osseoconductive graft materials to generate vital bone and achieve implant-to
      bone contact.

PMID- 17193935
TI  - Is your ONS chapter on the road to success or experiencing some bumps along the
      way?

PMID- 17193936
TI  - Unexpected "donut hole" raises concerns that patients will fail to fill needed
      prescriptions.

PMID- 17193937
TI  - World Cancer Declaration.

PMID- 17193938
TI  - Using evidence-based practice to reduce central line infections.

PMID- 17193939
TI  - Hypertension: just the facts.

PMID- 17193940
TI  - Management of acute decompensated heart failure in patients with cancer.

PMID- 17193942
TI  - Putting evidence into practice: evidence-based interventions for sleep-wake
      disturbances.
AB  - Symptom management is a vital aspect of the practice of oncology nursing. The
      Oncology Nursing Society has identified outcomes sensitive to nursing
      intervention, known as nursing-sensitive patient outcomes. This article presents
      information about sleep-wake disturbances that occur in patients with cancer and
      makes recommendations for evidence-based interventions to improve sleep for
      patients. Sleep-wake disturbances occur in 30%-75% of people with cancer and have
      a negative impact on other symptoms and quality of life. Despite the frequency
      and severity of sleep-wake disturbances, limited research has tested
      interventions to improve sleep-wake outcomes. Although no interventions currently
      receive the highest recommendations for implementation into practice, several
      nonpharmacologic interventions show initial positive findings in promoting high
      quality sleep and daytime functioning. Oncology nurses can screen for sleep-wake
      disturbances and suggest tailored interventions. Four categories of promising
      interventions are cognitive-behavioral therapy, complementary therapies,
      psychoeducation and information, and exercise. Clinicians can use the Putting
      Evidence Into Practice (PEP) card and PEP resources at www.ons.org/outcomes to
      improve sleep-wake outcomes.

PMID- 17193941
TI  - Putting evidence into practice: prevention of infection.
AB  - The prevention of infection is an important outcome to measure in patients with
      cancer because infectious complications are a significant cause of morbidity and
      mortality. Nurses play a vital role in the prevention of infection in patients
      with cancer through nursing practice, research, and patient education. However,
      many common nursing interventions to prevent infection are based on tradition or
      expert opinion and have not been subjected to scientific examination. The 2005
      Oncology Nursing Society Prevention of Infection Outcomes Intervention Project
      Team reviewed, critiqued, and summarized the research evidence for nursing
      interventions to prevent infections in patients with cancer. Pharmacologic and
      nonpharmacologic interventions were included because many advanced practice
      nurses prescribe medications. This article is an evidence-based review of nursing
      interventions to prevent infection in patients with cancer.

PMID- 17193943
TI  - Ethical dilemmas and moral distress in oncology nursing practice.
AB  - Although ethical values and principles guide oncology nursing practice, nurses
      often are challenged to fulfill every professional core duty and responsibility
      in their everyday practice. Nurses commonly encounter clinical situations that
      have ethical conflicts, and they often have difficulty recognizing and
      articulating them. Unresolved conflicts can cause feelings of frustration and
      powerlessness, which can lead to compromises in patient care, job
      dissatisfaction, disagreements among those in the healthcare team, and burnout.
      This article reviews the ethical principles and values individual nurses bring to
      their practice as well as those basic to the profession of nursing. This article
      also discusses ethical conflicts in oncology practice and describes how nurses,
      especially students and novice nurses, may react to such situations with moral
      uncertainty or distress. In addition, a process for analyzing and resolving
      ethical problems in clinical situations is outlined. Increasing awareness and
      dialogue about ethical issues is an important first step in the process.
      Additional resources in the clinical setting may encourage nurses to actively
      participate in ethical decision making and take deliberate action as moral
      agents.

PMID- 17193944
TI  - Immune reconstitution: the foundation for safe living after an allogeneic
      hematopoietic stem cell transplantation.
AB  - With increasing frequency, oncology nurses are providing long-term care to
      hematopoietic stem cell transplantation (HSCT) recipients in nontransplantation
      settings. This may be a result of more patients receiving HSCTs, recipients
      living longer, and recipients' desire to return to their hometowns as soon as
      possible. Although critical to patients' initial recovery after HSCT, immune
      reconstitution also must remain a priority of oncology nursing care long beyond
      the date of discharge from a transplantation center. As patients resume their
      normal lives, oncology nurses need to be diligent in assessment and education to
      facilitate the ultimate goal, a safe life after HSCT. This article provides
      concise details about the short- and long-term immunologic effects of HSCT and
      focuses on the long-standing threat of opportunistic infections that can persist
      months and years after HSCT.

PMID- 17193946
TI  - Self-determination and information seeking in end-stage cancer.
AB  - When patients learn that their cancer has recurred after primary treatments or is
      no longer responding to therapy and no alternative treatment options exist, their
      motivation to carry on living may be impacted greatly. Using the Self
      Determination Theory, this article's reflective analysis explores the unique
      situation of a woman with end-stage cancer and her continuous motivation to seek
      information about her illness. Information was gathered during clinical
      observations and informal conversations. The analysis showed how the patient
      sought information about her illness, how she manifested motivation, and how the
      hospital's social environment influenced her behavior. To understand the
      experience of being confronted with a terminal illness, the following issues are
      identified: expansion of awareness, life-facing knowledge contradictions, being
      open-minded and an active explorer of information sources, medical truth, and
      professional attitudes toward patients' informational needs. Nurses must
      understand patients' reasons for self-determination when facing illness
      uncertainty. Reflecting on such situations will strengthen nursing practice.

PMID- 17193945
TI  - Care for patients undergoing extracorporeal photopheresis to treat chronic graft
      versus-host disease: review of the evidence.
AB  - Late immune dysregulation following allogeneic hematopoietic cell transplantation
      (HCT) is known as chronic graft-versus-host disease (GVHD), which is a major
      cause of mortality and morbidity after HCT, and a rise in its incidence is
      predicted. Better therapies are being sought to manage chronic GVHD and limit
      patients' exposure to corticosteroids. Extracorporeal photopheresis (ECP), an
      immune-modulating therapy, has shown preliminary safety and efficacy in treating
      chronic GVHD. However, access to ECP is limited, care is costly, and the optimal
      frequency, duration, and durability of response are unknown. Although nurses who
      care for patients with chronic GVHD recognize its adverse impact on patients'
      quality of life, limited evidence exists about the selection of patients most
      likely to benefit from ECP therapy and from the supportive care provided to them.
      A multidisciplinary approach is needed to define the desired outcomes of ECP
      therapy and to determine the evidence base for nursing management approaches.

PMID- 17193948
TI  - Does every breast lump need to be worked up despite previous diagnoses?

PMID- 17193947
TI  - Nursing considerations for clofarabine in the treatment of acute lymphoblastic
      leukemia in children.
AB  - Each year, almost 3500 children are diagnosed with leukemia, representing
      approximately 30% of pediatric cancer cases. Acute lymphoblastic leukemia is the
      most common form of pediatric leukemia, accounting for approximately 80% of
      cases. A significant number of children fail to respond to existing
      chemotherapies or are unable to maintain remission. Their prognosis is poor, with
      little hope for long-term survival.

PMID- 17193950
TI  - Conversations with a nurse in cancer complementary and alternative medicine.

PMID- 17193949
TI  - Vacuum-assisted closure therapy.

PMID- 17193951
TI  - Cancer-related weight loss.

PMID- 17193952
TI  - [5-ALA fluorescence guided tumor resection].

PMID- 17193953
TI  - [Recent advances in the medical treatment of glioma-temozolomide].

PMID- 17193954
TI  - [Intraoperative monitoring].

PMID- 17193955
TI  - [Boron neutron capture therapy for malignant glioma].

PMID- 17193956
TI  - [Problems and plans in a new diagnosis procedure combination in neurological
      deseases. 1. Medical neurological diseases].

PMID- 17193957
TI  - [Problems and plans in a new diagnosis procedure combination in neurological
      deseases. 2. Neurosurgical diseases].

PMID- 17193958
TI  - [Brain bank].

PMID- 17193959
TI  - [Slowly progressive pure motor monoparesis at the right lower limb due to post
      traumatic cerebral hemorrhage].

PMID- 17193960
TI  - [An autopsied case of a 73 year-old man of familial parkinsonism with the onset
      of 24 years old, who was complicated with stroke, and died with ileus
      perforation].

PMID- 17193961
TI  - [Main results of the Biorisk experiment on the International Space Station].
AB  - To get better appreciation of the margins of phenotypic adaptation and genotypic
      changes in bacteria-fungi associations within the typical microbiota residing on
      structural materials of space-flown equipment, developed were a program and
      hardware for a series of experiments under the general name BIORISK. Protocol of
      each experimental cycle is based on the well-proven method of exposure of
      "passive" samples of materials (Biorisk-KM), microorganisms-materials systems
      inside the ISS service module (Biorisk-MSV), and microorganisms-materials systems
      on the outside of the ISS SM (Biorisk-MSN). Each six months the samples are
      returned to the laboratory in conjunction with crew rotation. Already the first
      in-hand data from the experiment point to the dramatic effect of space flight on
      growth, reproduction, and biological properties of test microbes and fungi. Thus,
      the activity of enzymes that characterize the pathogenic potential (RNA-ase and
      DNA-ase), and resistance of microorganisms to aseptic agents were found
      increased.

PMID- 17193963
TI  - [Communication within the mission control-space crew loop: the socio
      psychological aspects].
AB  - The object of the article is a pilot study of audio communication between space
      crew and ground operators. The experiment was to validate a new method of content
      analysis of radio contacts in order to evaluate the socio-psychological aspects
      of communication as within the crew, so between the crew and the Mission control
      center. The study supported the supposition of V.I. Myasnikov that the most
      frequent and active spokesman is a formal or informal crew lead. Also, each
      national MCC evidently prefers to contact its own crew member.

PMID- 17193962
TI  - [Morphobiochemical assay of the red blood system in members of the prime crews of
      the International Space Station].
AB  - According to the experiment Hematology protocol, blood samples from the Russian
      members of ISS prime crews 1 to 5 were gathered on L-30 and R+0, 7, 15 to study
      metabolic parameters (ATP, reduced glutathione, LHG and glucose-6-phosphate
      dehydrogenase activities). Lipid spectrum of membrane erythrocytes was determined
      in frozen erythrocyte mass; iron turnover and erythropoietin were investigated in
      frozen serum. Ratios of different erythrocyte forms were established in 32 microl
      of fixated whole blood using scanning electron microscopy. On R+0, the morpho
      biochemical parameters of red blood appear to still carry the imprints of space
      effects and, to an extent, certain difference in the setting of blood sampling
      from the Mir crew on landing in the space "shuttle" vehicle. Low level of iron
      and significantly increased erythropoietin on R+0 are the testimony of intensive
      hemoglobin production and an adequate bone morrow response to the increased
      oxygen demand. Shifts in erythron are of no clinical implications but indicative
      of the red blood adaptation to the factors of space fight.

PMID- 17193965
TI  - [Body fluids ratio and postural stability of head-down tilted apes in the periods
      of transition into the active vertical position].
AB  - It is known that the hypokinetic syndrome and alteration of the hydrostatic
      component by microgravity distort functioning of various body systems. Prevention
      of the adverse effects is achieved through implementation of a variety of
      physical exercises during tilting, and periodic transition into the upright
      position. The investigation was performed with 11 Macaques (Macaca mulatta) 3 to
      5 yrs. of age and 3.2-7.2 kg of weight. Brief (for 30 to 120 min 4 or 5 times a
      wk.) transition into the active upright position had a positive effect on the
      body liquids ratio modification in the course of 27-d HDT (-5 degrees). This was
      concluded from a less pronounced loss in the amount of extracellular liquid and
      its interstitial component. In addition, another positive result of this
      manipulation was less, in terms of volume and speed, significant gravity
      dependent blood flow toward the lower limbs during 10 minutes of standing test at
      the end of the experiment as compared with their controls w/o the preventive
      manipulation.

PMID- 17193964
TI  - [Action of estradiol, calcitonin and weight-loading on the development of
      osteopenia in tail-suspended female rats].
AB  - Experiments with tail-suspended female rats demonstrated that injection of
      sinestrol (synthesized estradiol) and myocalcic (sermon calcitonin) on a
      background of graded weight bearing (suspension interruption for 2 hrs. a day)
      prevented osteopenia in the spongy metaphyses of the shin-bone deprived of
      loading.

PMID- 17193966
TI  - [Role of the endocrine glands in divergence of plastic processes and energy
      metabolism in rats after extended exposure to hypergravity: cytologic
      investigation].
AB  - Cytologic and morphometric investigations of the hypothesis, thyroid, thyroid and
      pancreas of rats after 19-d centrifugation at 2G revealed suppression of
      somatotropic hormone production by hypophyseal somatotrophs and insulin by
      pancreatic beta-cells, and intensification of thyrotrophic hormone production by
      hypophyseal thyreotrophs, thyroxin by thyreoid parenchyma and glucagon by
      pancreatic alpha-cells. These change in hormone production are viewed as an
      endocrine mechanism of the divergence of plastic processes and energy metabolism
      in animals subjected to chronic exposure to hypergravity.

PMID- 17193967
TI  - [Characteristics of blood aggregation in human subjects of different age
      categories during normobaric interval hypo-oxytraining].
AB  - Blood aggregation was studied in human subjects of different age groups given
      normobaric hypooxytraining. The experiment was performed with participation of
      two groups of volunteers: experienced human subjects well-adapted to hypoxia and
      young non-adapted subjects. NOT protocol included 7 min of breathing hypoxic
      mixture (90% N2 and 10% O2) and 3 min of breathing atmospheric air at room
      temperature, 6 cycles every other day during one month. Blood aggregation was
      assessed by 26 parameters with the use of a multifunctional diagnostic system
      that permitted biophysical (rheologic), biochemical (coagulative) and mathematic
      (systemic) diagnostics. Two groups of the human subjects displayed significantly
      different reactions to of blood aggregation to the extreme factor (NOT). There
      was a marked dependence of the blood aggregation reaction to the hypoxic factor
      on the body protective-adaptive potential. Our data substantiate the need to
      develop NOT protocols for pilots of specific ages.

PMID- 17193968
TI  - [Effects of hyperoxic gas mixtures on the proliferative and migrative activities
      of cultivated endothelial cells of humans].
AB  - Proliferation and migration of endothelial cells of humans were studied in
      hyperoxic gas mixtures varying in percentage of oxygen and argon. Exposure to one
      or the other hyperoxic mixture was repeated, short (3 hrs) or long (18 hrs). The
      most significant inhibition of proliferation was observed after three long
      exposures in 100% O2 and the least signficant inhibition was caused by the gas
      mixture containing 89% of O2, 4.5% of Ar and 6.5% of N2 as an end-product of air
      separation with the short-cycle natural adsorption. Single 3-hr exposure to the
      hyperoxic mixture (5% Ar + 95% O2) activated EC migration, whereas repeated short
      exposure and single long exposure inhibited EC migration in vitro.

PMID- 17193969
TI  - [Relative biological effectiveness of accelerated heavy ions and fast neutrons
      estimated from frequency of aberration mytoses in the retinal epithelium].
AB  - Analyzed was the literature and authors' experimental data concerning lesion and
      recovery of epithelium cells of mice retina immediately and long after
      irradiation at different sources including single and partly fractionated
      irradiation by gamma- and X-rays, accelerated protons, helium, carbon and boron
      ions, and fast neutrons of the reactor range in a large spectrum of doses and
      LET. Reviewed are some new techniques of determining the RBE coefficient for
      these types of radiation; large values of the RBE coefficients for accelerated
      ions and neutrons (5-10 times higher than RBE coefficients calculated for the
      next day following irradiation) are a result of integration into calculation of
      the available data about the delayed disorders in retinal epithelium cell
      regeneration.

PMID- 17193970
TI  - [Cytogenetic and biochemical assay of an unidirectional effect of chronic
      combined exposure of laboratory animals to isoeffective concentrations of
      chemical substances].
AB  - Chronic combined exposure to low concentrations of chemical substances (equal to
      the maximal admissible limits for space vehicles) is fraught with an increase in
      chromosomal aberrations in bone marrow cells as compared with the spontaneous
      chromosome aberration rate. In addition to the cytogenetic evidence, there were
      also statistical phase shifts in metabolic parameters of erythrocytes (enzymes
      involved in the basal metabolism and a number of metabolites), leukocyte count in
      peripheral blood, and the total quantity of karyocytes in the bone marrow. No
      significant changes were found in organs of the immune and reproductive systems.

PMID- 17193971
TI  - [Experimental studies of the relative biological effectiveness of accelerated
      charged particles varying in energy].
AB  - Experimental results and literary data were analyzed for the relative biological
      effectiveness of heavy charged particles in a broad range of energy and LET to
      cells of humans and other mammals in culture, whole body of laboratory animals,
      microorganisms, bacteriophages, and plants. Analyzed were data obtained with the
      use of a diversity of tests of acute and delayed lesions induced by ionizing
      radiation, cancers and cataracts, specifically. Non-parametric methods are
      applied in parallel to the classic method of calculating the coefficients of
      relative biological effectiveness by correlating the equal-effective doses of the
      standard and a given radiation. Consideration is given to factors that may modify
      RBE values estimated for different types of radiation.

PMID- 17193972
TI  - [On-drift spectrometer with double successive separation with ionization in the
      corona discharge].
AB  - An experimental high-resolution ion-drift spectrometer is described. Operating
      characteristics were improved by installation of a second grid gate in the center
      of the drift space. The ion-drift analyzer setups and the ranges of amplitude,
      length and temporary delay of control impulses were identified in the course of
      testing. The article gives illustration of mobility spectrum in case of a single
      or paired gate analysis.

PMID- 17193973
TI  - [Effects of noise generated by life support systems on the human hearing
      function].
AB  - The review is devoted to the effects on the human hearing function of noise
      generated by the life support systems (LSS). Based on the analysis of literature
      on testing the experimental and operational LSS of the Russian and NASA space
      vehicles and stations the authors conclude that the negative effects of LSS
      generated noise have been kept in the focal point of the medical community of the
      International Space Station program consolidating efforts of IPs toward the
      development of advanced methods of protection and control of the crewmembers'
      acoustic organs.

PMID- 17193974
TI  - [Characteristics and patterns of the human bone reactions to microgravity].
AB  - Hypothesized processes of changes found in spacecrew bones following 5 to 7 mo.
      orbital missions are reviewed. Selective osteopenia of trabecular bones in the
      lower skeleton is attributed to a greater weight loading at 1 g. Increased
      mineral content in the upper skeleton (dual energy X-ray adsoptiometry--DXA) and
      hypermineralization of the limbic spongious bone (computer tomography) appear to
      be secondary and reflect the body liquids redistribution headword including to
      the abdomen. The additional negative gradient of the lower skeleton mass during
      early readaptation (about 1.5 mo, after landing) can be explained by remodeling
      (resorption and bone formation) as a reaction to the "load return". Personal
      variability is probably a fingerprint of genetic determinism of bone mass and
      metabolic phenotype that may sometimes lead to an increased risk of fracture. The
      authors raise the discussion about practicality of the genetic osteopenia
      prediction for space flyers.

PMID- 17193975
TI  - [Assessment and prediction of health status of the Mars mission crew members].
AB  - The scientific concept of health assessment and prediction in a piloted mission
      to Mars has been built on the principles of pre-nosologic diagnostics, i.e.,
      identification of the norm-pathology borderline states. The article deals with
      the medical care policy for the mission, and specific techniques and
      technologies. A three-level system of health assessment and prediction is
      proposed. Innovative approaches to evaluation of the body control systems during
      long exposure in microgravity have a footing of ground-based and space
      experimental investigations. Namely, these include evaluation of the
      cardiorespiration autonomous regulation and body functional reserve assessment by
      noninvasive recording of physiological signals in sleeping crewmembers before and
      after mission.

PMID- 17193976
TI  - [Stress effects of 72-hour sleep deprivation].
AB  - Stress effects of 3-d (72-hr) continuous vigilance were studied for renal
      excretion of 17-oxycorticoids (17-KS), electrolytes (potassium and sodium), and
      liquid. The investigation involved 12 male subjects aged 23 to 36. Baseline
      parameters displayed diurnal variations with comparatively high day and
      comparatively low night values. During the 72-hr vigilance, significant and
      consistent (statistically fiducial) intensification of 17-KS and potassium
      excretion occurred in the night-time, i.e., in the period of naturally low
      values, but only in the first two sleepless nights. As for sodium and liquid
      excretion, stress-related reduction in these parameters was more consistent and
      distinct in the day-time, i.e., in the period of naturally high values, rather
      than in the nighttime. Therefore, the two factors that should be accounted for by
      investigators of continuous vigilance (and, maybe, other stresses) are the
      anticipated direction of a stress-reaction and baseline diurnal variation of
      parameters under study. If stress is expected to increase a parameter,
      measurements should be done when the parameter is naturally low and, vice versa,
      if stress is known to reduce a parameter, then measurement should be planned in
      the period when it is naturally high. If direction of stress-related changes is
      predictable, investigations can be performed on a twenty-four hour basis.

PMID- 17193977
TI  - [Development of salt concentrates for mineralization of recycled water aboard the
      space station].
AB  - Recycled water can be brought up to the potable grade by adding minimal
      quantities of three soluble concentrates with the maximal content of inorganic
      salts. The authors present results of 3-year storage of potable water mineralized
      with makeup concentrates and analysis of potable water prepared with the use of
      the salt concentrates stored over this period of time. A water mineralization
      unit has been designed based on the principle of cyclic duty to produce
      physiologically healthy potable water with a preset salt content.

PMID- 17193978
TI  - [Studies of the eating behavior of Japanese quail chicks in the early postnatal
      period].
AB  - Time of the eating reaction (response to video signals) and eating behavior
      shortly after hatching were studied in Japanese quail chicks whose embryonic
      development took place under normal or changed gravity. Chicks partially
      incubated in a changed gravity showed a much slower eating reaction when compared
      with the chicks the prenatal development of which occurred under the normal
      gravity. In the chicks incubated at 1 g and placed in individual cages
      immediately after dominating afferentation for the eating behavior was visual
      Observations in the study will be used as a basis for designing a technology for
      handling and maintenance of hatchlings of the Japanese quail as a potential
      heterotrophic component of space life support systems.

PMID- 17193979
TI  - [Medical flight certification of civil pilots with cardiovascular pathologies].
AB  - Comprehensive examination of civil pilots including the clinical-physiological
      and mental tests was performed with the purpose to improve the system of expert
      evaluation of health and fight fitness of pilots with cardiovascular pathologies.
      Mental tests consisted of an MMPI modification, the standard multifactor
      personality test, portrait choice (adapted Szondi's eight inclinations test), and
      predictive drawing tests of the unconscious. Type of personality of the persons
      with cardiovascular pathologies were characterized in terms of individual traits,
      social behavior, thinking type, stress reaction, protective tactics, and form of
      deadaptation. Persons with a variety of premorbid cardiovascular pathologies
      (essential hypertension, atherosclerosis, and neurocirculatory dystonia) reveal
      specific traits that should be taken into consideration in the process of medical
      flight certification.

PMID- 17193980
TI  - [Russian treadmill BD-1 as a backup of the NASA TVIS].
AB  - Already during the early ISS increments malfunctioning of NASA TVIS (treadmill
      with vibration isolation system) posed major problems for regular crew training
      and particularly scamper, one of the key exercises on the Russian physical
      training program. During ISS increment-3, TVIS unscheduled repairs took virtually
      all the training time. In search for TVIS backup, Russian and NASA engineers
      considered jointly Russian treadmill BD-1, originally designed for Russian
      "shuttle" Buran and accepted it as a suitable backup in case of complete TVIS
      failure. To enter into the "dialogue" with BD-1, i.e., to record and downlink
      training data, the treadmill speed indicator, a part of the treadmill stand, was
      replaced by PC.

PMID- 17193981
TI  - [Radiation protective quality of spacesuit "Orlan-M" during extravehicular
      activities on the International Space Station].
AB  - Sampling irradiation of spacesuit "Orlan-M" allowed construction of a simulation
      model of the spacesuit shielding function for critical body organs. The critical
      organs self-shielding model is a Russian standard anthropomorphic phantom.
      Radiation protective quality of the spacesuit was assessed by calculating the
      dose attenuation rates for several critical body organs of an ISS crewmember
      implementing EVA. These calculations are intended for more accurate assessment of
      radiation risk to the ISS crews donning "Orlan-M" in near-Earth orbits.

PMID- 17193982
TI  - [Ultrastructure of spindles in m. soleus of rats after repeated simulation of the
      weightlessness effects].
AB  - Postponed for a long time repeated simulation of the weightlessness effects in
      rats by tail-suspension increases in the amount of intrafusal muscle fibers in m.
      soleus spindles, reflecting presumably elevation of the sensitivity of
      mechanoreceptors.

PMID- 17193983
TI  - [Person-oriented approaches to the psychologic assistance to pilots' teaching and
      training].
AB  - The author dwells upon the concept and practice of psychologic assistance to
      pilots' training and drilling, associated contradictions and issues that can be
      resolved by dint of ingenious training methods. One of these approaches is a
      person-oriented process of teaching, training and character building. The method
      was tested with a group of pilot students and some test results are described in
      the paper. To assimilate this approach, a special course for teachers, simulation
      and flight instructors needs to be developed.

PMID- 17193984
TI  - [Orthodontics for mentally handicapped patients].
AB  - The mentally handicapped exhibit a 3 times higher incidence of malocclusions and
      related functional problems than the general population. In contrast there is
      little available literature relating to the orthodontic treatment of handicapped
      patients. Based on published articles on orthodontic treatment of disabled
      patients the following recommendations can be given. First of all for each
      patient a 'problem list' should be drawn up, based on the diagnosis. In this list
      the orthodontic problems are formulated. Additionally, the list makes clear who
      is responsible for providing services related to orthodontic care, such as oral
      hygiene and transportation of the patient to the orthodontist. When deciding
      whether or not orthodontic treatment should be administered to a patient with a
      mental handicap the same functional and aesthetic considerations as with any
      other orthodontic case must be taken into account. Furthermore, the severity of
      the handicap and possible associated psychosocial and medical limitations as well
      as the extent to which it will be possible to treat the patient have to be
      considered. Contraindications are a severe mental handicap, inability to remain
      still in the dental chair, insufficient co-operation of parents/carers, open bite
      resulting from abnormal oral function, and a mild malocclusion. The orthodontic
      treatment should aim for an acceptable result, and not for orthodontic
      perfection.

PMID- 17193985
TI  - [Specialties in dentistry. 4. Post-academic specialization in geriatric
      dentistry].
AB  - In recent years, a specialization in geriatric dentistry has been established and
      along with it an educational programme. A specialist in geriatric dentistry is a
      dentist general practitioner with special knowledge and skills for delivering
      oral care to frail elderly people. The educational programme aims at an increase
      in dentists serving in geriatric care who are well prepared for delivering care.
      In the programme attention is paid to the special aspects of care delivery and
      the special somatic, mental, and social characteristics of frail elderly people.
      The goal is to formulate an individual oral care programme for every frail
      elderly person. An individual oral care programme may contain 5 different oral
      care activities: continuing care, prevention, support, treatments, and
      evaluation. These activities define the scope of specialists in geriatric
      dentistry. This scope in turn defines the profile of required knowledge and
      skills, and the profile is the foundation of the educational objectives of the
      educational programme. The educational programme contains 7 modules: affinity;
      somatic and mental disabilities; communicative skills and coping with behavioural
      disturbances; emergency medical care; history taking, assessment, prevention,
      treatments and evaluation; organization and legislation; scientific training.

PMID- 17193986
TI  - [Specialties in dentistry. Salivary flow and swallowing in Parkinson's disease].
AB  - Parkinson's disease is a slowly progressive and irreversible disorder of the
      nervous system. Drooling is listed as a secondary symptom of Parkinson's disease.
      Its cause is insufficiently clear. In the literature 2 possible causes are
      described: hypersalivation and swallowing abnormalities. These parameters have
      not been measured in a single study before. This article presents a review of the
      literature on the subject and describes the design for a future clinical study.
      The aim of this clinical study is to gain an insight into the cause and the
      prevalence of drooling in Parkinson's patients. A group of 50 Parkinson's
      patients will be compared to a group of 50 controls. The objectives of this
      comparative study comprise the assessment of salivary flow volumes, swallowing
      capacity, subjective experiences with drooling and an objective observation of
      drooling, the drooling quotient. Finally, the possibilities for treatment will be
      described.

PMID- 17193987
TI  - [Smoking and orthodontics].
AB  - In view of the severe adverse effects that smoking has on health, much energy is
      being invested especially to prevent adolescents from starting to smoke or to get
      them to stop. Since orthodontists have regular contact with a rather large group
      of young people during the period when they begin to smoke, a study was conducted
      to determine whether these specialists could be engaged in an organized anti
      smoking programme. One of the relevant considerations was that orthodontists are
      succesful in motivating adolescents to wear braces. Research has shown that
      dentists in an organized programme in the United States were able to achieve a
      significant reduction in the percentage of adult smokers. The research findings
      revealed, however, that the orthodontists nevertheless lacked sufficient training
      and motivation to be effectively employed in an anti-smoking programme. The
      results of some clinical trials with adolescent patients were disappointing, but
      they did make clear what needs to be done to achieve improvements. Well organized
      involvement in a sound anti-smoking programme in The Netherlands will require
      very careful preparation and will only be able to start after well designed and
      successful clinical trials.

PMID- 17193988
TI  - [Dissertations 25 years after date 12. Classification and virulence of black
      pigmented bacteria in relation to periodontitis].
AB  - Bacteria in dental plaque play an essential role in the origin and development of
      periodontitis. In the seventies of the last century it became clear that black
      pigmented bacteria of the genus Bacteroides play a vital role in this process.
      These bacteria are currently known as Porphyromonas gingivalis and Prevotella
      intermedia. In a PhD dissertation 25 years ago it was shown by DNA analysis that
      this group of bacteria is very heterogeneous, and that different species exist,
      which are associated with different oral infections. Because Porphyromonas
      gingivalis plays an important role in periodontitis, this bacterium has been
      investigated extensively during the last decades. The entire genome is now known
      at the DNA level. In addition, transmission between spouses has been shown to be
      possible, although it does not always cause periodontal disease. It is not yet
      possible to conclude if for patients with Porphyromonas gingivalis a different
      antibiotic policy should be used compared to patients without this bacterium.

PMID- 17193989
TI  - [Kabuki syndrome, a congenital syndrome with multiple anomalies].
AB  - The characteristics of a 5-years old girl, referred to a multidisciplinary team
      for cleft lip and palate because of speaking problems, were diagnosed as Kabuki
      syndrome. The Kabuki syndrome is a congenital syndrome of unknown aetiology,
      diagnosed based on a combination of clinical findings. It is characterised by
      distinctive facial features, skeletal anomalies, dermatoglyphic abnormalities,
      developmental delay and mild to moderate mental retardation. Children with the
      syndrome often have oral manifestations such as cleft palate, missing permanent
      teeth and conic crowns of upper incisors. The Kabuki syndrome was first described
      regarding the Japanese population but it is now known to occur in many other
      races as well. In a recent publication, 20 Dutch patients with Kabuki syndrome
      were described.

PMID- 17193990
TI  - [Needle breakage during mandibular block anaesthesia: prevention and retrieval].
AB  - Disposable needles for dental local anaesthesia do not break easily. Still,
      needle breakage does occur, and is mainly caused by unexpected movements of the
      patient or pre-use bending of the needle by the dentist. If a dental needle
      breaks while administering local anaesthesia, the dentist should prevent panic.
      If the patient opens his mouth wide the needle might still be visible. If so, the
      needle is removed. If the needle is no longer visible, the site where the needle
      has penetrated the mucosa should be marked with a permanent marker. The dentist
      will contact a maxillofacial surgeon for immediate consultation. The
      maxillofacial surgeon will try to retrieve the broken dental needle under general
      anaesthesia.

PMID- 17193991
TI  - Cleansing supercentres.

PMID- 17193992
TI  - Revised NMC standards provide clarity on assessment.

PMID- 17193993
TI  - How to open a tin of Kocher sardines.

PMID- 17193994
TI  - Double gloving to reduce surgical cross-infection.

PMID- 17193995
TI  - She fought the law. . . but the law won.

PMID- 17193996
TI  - Reflection on action: communication is the key.
AB  - This article will explore, by reflection, a critical incident by considering the
      positive and negative aspects. This will encourage me as a trainee surgical care
      practitioner to look at how and why the incident occurred and it will support me
      in exploring my emotions. Having experienced this incident, on reflection I can
      look back at my mixture of emotions--ranging from fear and annoyance to
      accomplishment--because no matter how able we are as practitioners there will
      always be new and challenging experiences. When we value our work we value
      ourselves as practitioners who can make important contributions to the care of
      patients.

PMID- 17193998
TI  - Reducing the risk of surgical fires: are you assessing the risk?
AB  - In this article the authors reflect on a critical incident involving a fire in
      the operating theatre and review best practice for ensuring organisations assess
      potential fire hazards and manage the risks.

PMID- 17193997
TI  - Checking the anaesthetic machine.
AB  - Making sure that anaesthetic equipment is working correctly is an essential part
      of the anaesthetic practitioner's role. During induction of anaesthesia the
      patient is at one of the most vulnerable points in his or her perioperative care.
      This is the point at which equipment error may put the patient at high risk of
      harm, for example, through compromising the airway, causing circulatory problems,
      preventing satisfactory oxygenation or even causing death. Many writers have
      drawn comparisons between anaesthesia and aviation, with the suggestion that
      practitioners should check the anaesthetic machines using a 'cockpit drill'
      (Ranasinghe 2000). The purpose of this detailed check is to ensure the machine is
      safe to use. The careful attention to the check is a reflection of good practice
      which the practitioner's codes of professional practice demand (HPC 2004, NMC
      2004). This article discusses the importance of following the anaesthetic
      checklist to the recommended standards for both the practitioner and the patient.

PMID- 17193999
TI  - Practice education: delivering the vision.
AB  - While acknowledging the inherent challenges of the practice education rhetoric
      being translated into reality, the aim of this paper is to examine the
      challenges, issues and innovations surrounding the delivery of education in
      practice within a departmental context. Organisational context, national
      initiatives, political directives and departmental challenges were added to the
      intrinsic educational issues which were required to be addressed in order for the
      authors' shared educational vision to be delivered within their own sphere of
      responsibility.

PMID- 17194000
TI  - Charnley's hip prosthesis.
AB  - When he sat the FRCS examination in 1951 Harold Ellis was advised that, if asked
      by the examiner, 'What is the best treatment for osteoarthritis of the hip?' to
      reply, 'Provide the patient with a walking stick and prescribe aspirin.' The
      results of surgery for this condition at that time were pretty discouraging.
      Here, Professor Ellis outlines the development of this surgical technique.

PMID- 17194001
TI  - [A neonate with the heart in the right hemithorax].
AB  - Three neonates presented with the heart in the right hemithorax: a newborn girl
      with a chest deformity and secondary dextrocardia (Poland sequence), a
      prematurely born girl with uncomplicated Kartagener's syndrome, and a newborn boy
      with cyanosis and the heart in the right hemithorax, in whom a surgical
      correction was indicated. A diagnosis ofdextrocardia should include the
      differentiation between primary and secondary dextrocardia. Secondary
      dextrocardia, or dextroposition, is the result of chest deformities,
      diaphragmatic defects, severe lung disease, or the presence of a mass displacing
      the heart from its normal position, usually without any cardiac abnormalities. In
      primary dextrocardia, the position of the organs in the abdomen is important for
      the differential diagnosis and the prognosis. The incidence of congenital cardiac
      malformations in primary dextrocardia varies from 10%, in situs inversus totalis,
      up to 90% in solitary dextrocardia.

PMID- 17194002
TI  - [Leishmaniasis: progress in diagnosis, treatment and prevention].
AB  - Visceral leishmaniasis ranks second after malaria in the top 10 fatal parasitic
      diseases worldwide. Treatment is effective, but most patients live in developing
      countries where even basic health care is unavailable. Economic factors hamper a
      targeted approach, which should include the following: preventing transmission by
      distributing bednets; developing diagnostic tools that can be used in the field
      without a laboratory; developing new and affordable drugs; and evaluating
      different drug combinations and treatment schedules that may prevent the
      development of resistance, as has been done in tuberculosis, HIV and malaria.

PMID- 17194003
TI  - [Poliomyelitis in 2006: all or nothing].
AB  - Since it was launched in 1988, the Global Polio Eradication Initiative has made
      great progress: millions of children have been saved from a serious disease and
      type 2 poliovirus has been eradicated. The original target of polio eradication
      by the year 2000 was, however, too optimistic: as of 2006, polio remains endemic
      in 4 countries (Nigeria, India, Pakistan and Afghanistan). In northern Nigeria,
      it is particularly difficult to reach enough children during National
      Immunisation Days to stop the circulation of wild poliovirus and prevent spread
      to neighbouring countries that are at risk for epidemics due to low routine
      vaccination coverage. However, critics of the initiative provide no real
      alternative. The WHO will continue the initiative using new strategies to realise
      -for the second time in history after smallpox--the eradication ofa serious
      infectious disease.

PMID- 17194004
TI  - [Some new aspects of the Klinefelter syndrome].
AB  - Klinefelter syndrome (KS) is the most frequent form of male hypogonadism. Still,
      at least 50% ofcases are not diagnosed, partly because of the great variation in
      the clinical symptoms, partly because physicians are unfamiliar with KS. Timely
      treatment with testosterone can contribute to a more positive body image and,
      consequently, to a healthier psychosexual development in men with KS. Men with KS
      experience significantly more health problems and an increased risk ofa
      malignancy. New reproductive techniques no longer automatically mean that men
      with KS will remain infertile. Treatment with testosterone is in principle life
      long to prevent osteoporosis and loss of muscle mass and strength.

PMID- 17194005
TI  - [Miltefosine: a new remedy for leishmaniasis].
AB  - There is a need for a safe and effective oral treatment for cutaneous and
      visceral leishmaniasis. Miltefosine is the first oral drug that is efficacious
      against different forms ofleishmaniasis, however it is not equally effective
      against all Leishmania species. Miltefosine is an alkylphosphocholine, originally
      developed for the treatment of cancer. The mechanism of action is probably based
      on interference with the synthesis and degradation of parasitic membrane lipids.
      Little is known about the pharmacokinetics ofmiltefosine; an important
      characteristic is its long elimination half-life of seven days or longer. The
      most frequent adverse effects are of gastrointestinal origin. Miltefosine should
      not be used during pregnancy. Over thirty leishmaniasis patients have already
      been treated with miltefosine in the Netherlands.

PMID- 17194006
TI  - [Diagnostic image (303). A deeply tanned woman].
AB  - A 50-year-old woman complained of nausea, diarrhoea, tiredness and dizziness five
      weeks after a visit to Egypt. She was deeply tanned with hyperpigmentation on the
      metacarpophalangeal joints, palm of hand creases and buccal mucosa, due to
      Addison's disease.

PMID- 17194007
TI  - [New medications; erlotinib].
AB  - Erlotinib inhibits the phosphorylation of the epidermal growth-factor receptor
      (EGFR/HERI), a tyrosinekinase protein. This results in an inhibition of signal
      transduction and therefore decreased cell division and increased cell death. The
      agent is indicated for the treatment of patients with advanced local or
      metastasised non-small-cell pulmonary carcinoma after other cytostatic therapy
      has failed.

PMID- 17194008
TI  - [No advantage to referring patients with acute myocardial infarction from a
      general hospital to an intervention clinic for percutaneous coronary
      intervention; comparison of mortality rates in 2000 and 2003 in the Meander
      Medical Centre, Amersfoort].
AB  - OBJECTIVE: To evaluate whether implementation of the 2000 Netherlands Society of
      Cardiology guideline 'ST-elevation acute coronary syndromes', which recommends
      the use ofpercutaneous coronary intervention (PCI), has reduced mortality and
      complication rates in a general hospital, and whether patient characteristics and
      outcomes are comparable to those reported in the Assessment of the Safety and
      Efficacy of a New Thrombolytic (ASSENT) 2 and 3 trials. DESIGN: Retrospective
      outcomes study. METHOD: Data from 2003 were compared with data from 2000
      regarding patients with acute myocardial infarction who received thrombolysis at
      the Meander Medical Centre in Amersfoort, the Netherlands, or percutaneous
      transluminal coronary angioplasty (PTCA) after referral to an intervention
      clinic. Data included baseline characteristics, type of treatment, outcomes and
      complications. Age, sex and mortality ofall patients were compared to data from
      the ASSENT 2 and 3 trials. RESULTS: Data were included from 130/132 patients
      treated in 2003 and 145/145 patients treated in 2000. Baseline characteristics
      were comparable, except age: there were significant more elderly patients in 2003
      (p = 0.006). After implementation of the guideline, significantly more patients
      underwent PTCA (odds ratio (OR) 4.41 (95% CI: 2.51-7.75)). After adjusting for
      confounding factors there was no significant difference in in-hospital mortality
      (adjusted OR 1.11 (95% CI: 0.48-2.60)), 30-day mortality and 1-year mortality.
      Significantly more minor complications were reported (OR 2.58 (95% CI: 1.07
      6.19)). Significantly more women and patients older than 75 years were treated
      compared with the ASSENT 2 and 3 trials. The 30-day mortality rate was
      significantly higher compared with ASSENT 2 (OR 1.60 (95% CI: 1.07-2.41)) and
      ASSENT 3 (OR1.74 (95% CI: 1.14-2.66)). CONCLUSION: The implementation of new
      guidelines 'ST-elevation acute coronary syndromes' did not result in lower
      mortality or fewer complications.

PMID- 17194009
TI  - [A Dutch family with the hereditary periodic fever or tumour necrosis factor
      receptor-associated periodic syndrome (TRAPS)].
AB  - A 9-month-old girl was referred to the paediatrician because of fever of unknown
      origin. Since the age of 4 years she had recurrent attacks of muscle, joint and
      abdominal pain, in addition to periodic fever. Her sister and her mother had
      similar symptoms. The tumour necrosis factor (TNF) receptor-associated periodic
      syndrome (TRAPS) was suspected and confirmed by DNA analysis. Several members of
      the extended family were carriers of the same mutation. In patients with
      recurrent unexplained periods offever in combination with myalgia, arthralgia and
      abdominal pain, and in whom these symptoms also occur in members of the family,
      TRAPS should be considered as the cause. Glucocorticosteroids and etanercept, a
      TNF-receptor antagonist, may be effective in the treatment of attacks. Early
      recognition of this syndrome is important because of the risk of developing
      amyloidosis.

PMID- 17194010
TI  - [A patient with long-term, unrecognized leishmaniasis].
AB  - A man from Surinam presented at the Department of Internal Medicine with a
      perforated septum and progressive collapse of the nose. This condition had
      existed for 22 years, though earlier analysis had not revealed the cause.
      Microscopic analysis showed a granulomatous inflammatory reaction, with cultures
      revealing of Leishmania. The diagnosis was mucocutaneous leishmaniasis and PCR
      indicated Leishmania braziliensis complex. The patient was treated for
      mucocutaneous leishmaniasis by a 28-day course of intravenous sodium
      stibogluconate therapy. Initially, treatment was stopped briefly due to
      neurotoxicity, but was recommenced and successfully completed. After treatment
      the infection parameters returned to normal and the patient was referred for
      reconstructive nasal surgery. Due to a low parasitic load mucocutaneous
      leishmaniasis can be difficult to detect, especially in chronic cases. However,
      the use of molecular techniques has improved both the sensitivity and specificity
      of detection. The ability to distinguish between different species and sub
      species is of prognostic and therapeutic relevance.

PMID- 17194011
TI  - [A good medical curriculum takes the religious beliefs and cultural background of
      the students into consideration].
AB  - The ethnic composition of the student population is highly diverse, just like
      that of the Dutch population, and the medical curriculum should take this into
      consideration. The curriculum assumes that doctors will be able to recognise
      problems that are related to a particular cultural background. The flexibility
      that medical curricula are expected to display in the way they deal with cultural
      diversity may also be expected of both Dutch and originally non-Dutch students.
      Opening up dilemmas for discussion and searching for solutions in a constructive
      manner during the medical curriculum can contribute to a professional approach to
      patients later in life.

PMID- 17194012
TI  - [The medical curriculum need not take the religious beliefs and cultural
      background of the students into consideration].
AB  - Newly graduated doctors must be able to solve a limited number of patient
      specific problems in an adequate manner. The patient is at the centre of
      attention here, not the doctor. Accepting religious beliefs and cultural
      differences as an excuse for not learning something would mean that other excuses
      would also be accepted more readily, thus changing the primary goals of the
      medical curriculum.

PMID- 17194014
TI  - [Coma in a child after treatment with the 'magic salve' lidocaine-prilocaine
      cream].

PMID- 17194013
TI  - [Coma in a child after treatment with the 'magic salve' lidocaine-prilocaine
      cream].

PMID- 17194015
TI  - [Diagnostic image (290). A woman with painful finger joints and swelling].

PMID- 17194016
TI  - [Favourable results with surgical treatment in 43 children with hypoplastic left
      heart syndrome or similar disorders, 1999-2005].

PMID- 17194017
TI  - A kinetic, modeling and mechanistic re-analysis of thymidine phosphorylase and
      some related enzymes.
AB  - Thymidine phosphorylase (TP) is an important target enzyme for cancer
      chemotherapy but currently available inhibitors lack in vivo potency. Related
      enzymes also are therapeutic targets. A greater understanding of enzyme structure
      and mechanism may help in the design of improved drugs and this work assists in
      that regard. Also important is the correct identification of the ionization
      states and tautomeric forms of substrates and products when bound to the enzyme
      and during the course of the reaction. Approximate methods for estimating some
      deltapK(a)s between aqueous and protein-bound substrates are exemplified for
      nucleobases and nucleosides. The estimates demonstrate that carbonyl-protonated
      thymidine and hydroxy tautomers of thymine are not involved in TP's actions.
      Other estimates indicate that purine nucleoside phosphorylase binds inosine and
      guanosine as zwitterionic tautomers and that phosphorolysis proceeds through
      these forms. Extensive molecular modeling based on an X-ray structure of human TP
      indicates that TP is likely to be mechanistically similar to all other natural
      members of the class in proceeding through a alpha-oxacarbenium-like transition
      state or states.

PMID- 17194018
TI  - Synthesis and anticancer activity of certain mononuclear Ru (II) complexes.
AB  - Bis(1,10-phenanthroline/2,2'-bipyridine) ruthenium(II)complexes containing TCP,
      TTZ OPBI, and BTSC ligands (where, TCP = 1-thiocarbamoyl-3,5-diphenyl-2
      pyrazoline, TTZ = 2-(3,5-diphenyl-4,5-dihydropyrazol-1-yl)-4-phenylthiazole, OPBI
      = 2-hydroxyphenyl benzimidazole and BTSC = benzoin thiosemicarbazone) have been
      prepared and characterized. The spectral data suggested that the ligands were
      coordinated with the metal through nitrogen, sulfur and oxygen atoms. The target
      complexes were tested in vivo for anticancer activity against transplantable
      murine tumor cell line, Ehrlich's Ascitic Carcinoma (EAC). All these complexes
      increased the life span of the EAC-bearing mice, decreased their tumor volume and
      viable ascitic cell count as well as improved Hb, RBC and WBC counts. These
      results suggest that the Ru(II) complexes exhibit significant antitumor activity
      in EAC-bearing mice. It was also observed that the ruthenium complexes protected
      red blood cells from 2,2'-azo-bis(2-methylpropionamidine) dihydrochloride (AAPH)-
      induced hemolysis. The inhibitory effect was dose-dependent at a concentration of
      20-120 microg/ml.

PMID- 17194019
TI  - Detection of sarin in plasma of rats after inhalation intoxication.
AB  - Presently used methods for detection and diagnosis of the severity of
      intoxication with organophosphorus (OP) compounds are mostly those that quantify
      inhibition of blood cholinesterases. It was found that when plasma inhibited with
      OP compounds is incubated in the presence of a high concentration of fluoride
      ions, the organophosphate is released from the enzyme thus yielding a
      phosphofluoridate, which can be analyzed by gas chromatography and NP detection.
      In our study, the concentration of sarin released after fluoride ions were added
      to the plasma of sarin-poisoned rats was determined. Sarin amounts in plasma
      measured after refluoridation and plasma butyrylcholinesterase activity in ten
      rats, that were exposed to sarin vapors at concentration of 1.25 microg/L (E1
      group) and 2.5 microg/L (E2 group) respectively, for 60 min. In the E2 group the
      concentration of sarin in plasma was nearly 2-fold higher than in the E1 group.
      These results correspond well with the concentrations of sarin vapors to which
      the animals were exposed. Both experimental groups of animals showed significant
      decreases in butyrylcholinesterase activity by more than 30%-36.4% (E1 group) and
      47.0% (E2 group). The method of fluoride-induced reactivation provides a very
      good marker for monitoring sarin intoxication in laboratory animals determined
      previously mostly by ChE determination which does not allow any information on
      sarin amounts in plasma.

PMID- 17194021
TI  - Synthesis, characterization and inhibitory potency of two oxono and thiono
      analogues of phosphoramidate compounds on acetylcholinesterase.
AB  - Two novel structurally related phosphoramidate compounds, 1 and 2, with likely
      beta-diketone system were synthesized and characterized by 1H, 13C, 31P NMR, IR
      spectroscopy and elemental analysis. Compound 2 exhibited a 31P NMR signal which
      was significantly shielded (8 ppm) relative to compound 1. Determination of human
      erythrocyte acetylcholinesterase (hAChE) inhibitory activity was carried out
      according to Ellman's modified kinetic method and the IC50 values of compounds 1
      and 2 were 1.567 and 2.986 mM, respectively. The k(i) values of 1 and 2 were 1.39
      to 2.65 min(-1) respectively. A comparison of the bimolecular rate constant
      (k(i)) and IC50 values for the irreversible inhibitors 1 and 2 revealed that the
      oxono analogue has greater affinity for hAChE than the thiono compound.
      Furthermore effects of two conventional oximes paralidoxime (A) and obidoxime (B)
      on reactivation of the inhibited hAChE were studied but low reactivity was shown
      by both the oximes.

PMID- 17194020
TI  - New group of xylene linker-containing acetylcholinesterase reactivators as
      antidotes against the nerve agent cyclosarin.
AB  - Nerve agents such as sarin, cyclosarin and tabun are organophosphorus substances
      able to inhibit the enzyme acetylcholinesterase (AChE; EC 3.1.1.7). AChE
      reactivators and anticholinergics are generally used as antidotes in the case of
      intoxication with these agents. None of the known AChE reactivators is able to
      reactivate AChE inhibited by all nerve agents used. In this work, reactivation
      potency of nine newly developed AChE reactivators with an incorporated xylene
      ring in their structure was measured in vitro. Cyclosarin was chosen as an
      appropriate member of the nerve agent family. Reactivation potency of the tested
      AChE reactivators was compared with the gold standard of AChE reactivators-
      pralidoxime. Two oximes (K107 and K108) surpassed the reactivation potency of
      pralidoxime. Moreover, from the obtained results it could be deduced that AChE
      reactivators with a functional oxime group in position-2 are the most potent AChE
      reactivators in the case of cyclosarin intoxications.

PMID- 17194022
TI  - Novel urease inhibitors from Daphne oleoids.
AB  - Phytochemical investigations on the chloroform and ethyl acetate soluble
      fractions of the roots of the Daphne oleoids led to the isolation of the coumarin
      glycosides 1-6. Compound 5 with IC50 values 22.05 and 26.30 microM repectively,
      was found to be the most active of these compounds when screened against Bacillus
      pasteurii and jack bean urease enzymes in a concentration-dependent fashion.

PMID- 17194023
TI  - A new Bacillus pasteurii urease inhibitor from Euphorbia decipiens.
AB  - Inhibition of Bacillus pasteurii urease enzyme by 3,7,15-tri-O-acetyl-5-O
      nicotinoyl-13,14-dihydroxymyrsinol (1), a diterpene ester with a myrsinol-type
      skeleton, isolated from Euphorbia decipiens Boiss. and Buhse, was un-competitive
      consistent with the molecular docking results. The Ki value was 117.40 +/- 0.7
      microM.

PMID- 17194024
TI  - Inhibition of jack bean urease by tetrachloro-o-benzoquinone and tetrachloro-p
      benzoquinone.
AB  - Tetrachloro-o-benzoquinone (TCoBQ) and tetrachloro-p-benzoquinone (TCpBQ) were
      studied as inhibitors of jack bean urease in 20 mM phosphate buffer, pH 7.0, 1 mM
      EDTA, 25 degrees C. The mechanisms of inhibition were evaluated by analysis of
      the progress curves obtained with two procedures: the reaction initiated by
      addition of the enzyme and the reaction initiated by addition of the substrate
      after preincubation of the enzyme with the inhibitor. The obtained results were
      characteristic of slow-binding inhibition. The effects of different inhibitor
      concentrations on the initial and steady-state velocities obeyed the
      relationships of two-step enzyme-inhibitor interaction, qualified as mechanism B.
      It was found that TCoBQ and TCpBQ are strong urease inhibitors. TCpBQ is more
      effective than TCoBQ with the overall inhibition constant of K(i)* = 4.5 x 10(-7)
      mM. The respective inhibition constant of TCoBQ was equal to: K(i)* = 2.4 x 10(
      6) mM. The protective experiment proved that the urease active site is involved
      in the tetrachlorobenzoquinone inhibition process. High effectiveness of thiol
      protectors against inhibition by TCoBQ and TCpBQ indicates the strategic role of
      the active site sulfhydryl group in the blocking process. The stability of the
      complexes: urease-TCoBQ and urease-TCpBQ was tested in two ways: by dilution or
      addition of dithiothreitol. No recovery of urease activity bound in the urease
      inhibitor complexes proves that the complexes are stable and strong.

PMID- 17194025
TI  - Adenosine deaminase in ischemia reperfusion injury in patients with myocardial
      infarction.
AB  - A comparative study on the levels of erythrocyte adenosine deaminase and lipid
      peroxidation has been undertaken in patients with myocardial infarction before
      and after thrombolysis along with matched healthy individuals. Our findings show
      that adenosine deaminase activity is highly elevated in post-reperfused patients
      when compared to pre- thrombolysed and healthy persons. Malondialdehyde(MDA)
      levels are also significantly increased in post-thrombolysed patients. The study
      reveals an important role of adenosine deaminase in reperfusion injury in
      patients with myocardial infarction.

PMID- 17194026
TI  - A fission yeast-based test system for the determination of IC50 values of anti
      prostate tumor drugs acting on CYP21.
AB  - Human steroid 21-hydroxylase (CYP21) and steroid 17alpha-hydroxylase/17,20-lyase
      (CYP17) are two closely related cytochrome P450 enzymes involved in the
      steroidogenesis of glucocorticoids, mineralocorticoids, and sex hormones,
      respectively. Compounds that inhibit CYP17 activity are of pharmacological
      interest as they could be used for the treatment of prostate cancer. However, in
      many cases little is known about a possible co-inhibition of CYP21 activity by
      CYP17 inhibitors, which would greatly reduce their pharmacological value. We have
      previously shown that fission yeast strains expressing mammalian cytochrome P450
      steroid hydroxylases are suitable systems for whole-cell conversion of steroids
      and may be used for biotechnological applications or for screening of inhibitors.
      In this study, we developed a very simple and fast method for the determination
      of enzyme inhibition using Schizosaccharomyces pombe strains that functionally
      express either human CYP17 or CYP21. Using this system we tested several
      compounds of different structural classes with known CYP17 inhibitory potency
      (i.e. Sa 40, YZ5ay, BW33, and ketoconazole) and determined IC50 values that were
      about one order of magnitude higher in comparison to data previously reported
      using human testes microsomes. One compound, YZ5ay, was found to be a moderate
      CYP21 inhibitor with an IC50 value of 15 microM, which is about eight-fold higher
      than the value determined for CYP17 inhibition (1.8 microM) in fission yeast. We
      conclude that, in principle, co-inhibition of CYP21 by CYP17 inhibitors cannot be
      ruled out.

PMID- 17194028
TI  - Carbonic anhydrase inhibitors. Selective inhibition of human tumor-associated
      isozymes IX and XII and cytosolic isozymes I and II with some substituted-2
      mercapto-benzenesulfonamides.
AB  - A series of 2-mercapto-substituted-benzenesulfonamides has been prepared by a
      unique two-step procedure starting from the corresponding 2-chloro-substituted
      benzenesulfonamides. Compounds bearing an unsubstituted mercapto group and the
      corresponding S-benzoyl derivatives were investigated as inhibitors of four
      isoforms of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), i.e., the
      cytosolic, ubiquitous isozymes CA I and II, as well as the transmembrane, tumor
      associated isozymes CA IX and XII. These derivatives were medium potency hCA I
      inhibitors (K(I)s in the range of 1.5-5.7 microM), two derivatives were strong
      hCA II inhibitors (K(I)s in the range of 15-16 nM), whereas the others showed
      weak activity. These compounds inhibited hCA IX with inhibition constants in the
      range 160-1950 nM and hCA XII with inhibition constants in the range 1.2-413 nM.
      Some of these derivatives showed a certain degree of selectivity for inhibition
      of the tumor-associated over the cytosolic isoforms, being thus interesting leads
      for the development of potentially novel applications in the management of
      hypoxic tumors which overexpress CA IX and XII.

PMID- 17194027
TI  - Antibacterial Co(II), Ni(II), Cu(II) and Zn(II) complexes of Schiff bases derived
      from fluorobenzaldehyde and triazoles.
AB  - Antibacterial Schiff bases derived from 1,2,4-triazoles as well as their metal
      complexes incorporating cobalt(II), nickel(II), copper(II) and zinc(II) have been
      synthesized and characterized. Physico-chemical studies suggest that an
      octahedral geometry for the cobalt(II), nickel(II) and zinc(II)and square-planer
      geometry for the copper(II) complexes. These complexes have been screened for
      antibacterial activity against three Gram-positive (Staphylococcus aureus,
      Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative
      (Salmonella typhi and Pseudomonas aeruginosa) bacterial strains, and results
      compared with the activity of the free ligands. The metal complexes were found to
      be more potent against one or more bacterial strains than the free ligands.

PMID- 17194029
TI  - WY 14,643 inhibits human aldose reductase activity.
AB  - Aldose reductase (AR) is implicated to play a critical role in diabetes and
      cardiovascular complications because of the reaction it catalyzes. Our data
      reveal that peroxisome proliferator WY 14,643, follows a pure non-competitive
      inhibition pattern in the aldehyde reduction activity as well as in the alcohol
      oxidation activity of AR. This finding communicates for the first time a novel
      feature of WY 14,643 in regulating AR activity. In addition, this observation
      indicates that AR, AR-like proteins and aldo-keto reductase (AKR) members may be
      involved in the WY 14,643 mechanism of action when it is administered as PPAR
      agonist.

PMID- 17194030
TI  - Sevoflurane modulates the activity of glyceraldehyde 3-phosphate dehydrogenase.
AB  - The mechanism of inhalation anesthesia remains to be fully elucidated. While
      certain neuronal membrane proteins are considered sites of action, cytosolic
      proteins may also be targets. We hypothesize that inhaled anesthetics may act via
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH), which has recently been shown
      to participate in neuronal inhibition. We examined the effects of sevoflurane, a
      halogenated ether anesthetic, on the catalytic and fluorescence properties of
      GAPDH. Initial rates of oxidoreductase activity decreased approximately 30% at
      saturating levels of sevoflurane. NADH-stimulated oxidoreductase activity (25
      microM NADH; 0.8mM NAD+) increased with sevoflurane. Sevoflurane quenched
      tryptophan fluorescence emission and increased polarization. Additionally,
      sevoflurane increased the susceptibility of GAPDH to thermal denaturation
      suggesting an effect on conformation. Our findings warrant further research on
      sevoflurane's effect on GAPDH and indicate that this approach may lead to
      delineation of a novel contribution to the mechanism of anesthesia.

PMID- 17194031
TI  - Inhibition of human glutathione transferases by multidrug resistance
      chemomodulators in vitro.
AB  - Reversal of the drug-resistance phenotype in cancer cells usually involves the
      use of a chemomodulator that inhibits the function of a resistance-related
      protein. The aim of this study was to investigate the effects of MDR
      chemomodulators on human recombinant glutathione S-transferase (GSTs) activity.
      IC50 values for 15 MDR chemomodulators were determined using 1-chloro
      dinitrobenzene (CDNB), cumene hydroproxide (CuOOH) and anticancer drugs as
      substrates. GSTs A1, P1 and M1 were inhibited by O6-benzylguanine (IC50s around
      30 microM), GST P1-1 by sulphinpyrazone (IC50 = 66 microM), GST Al-1 by
      sulphasalazine, and camptothecin (34 and 74 microM respectively), and GST M1-1 by
      sulphasalazine, camptothecin and indomethacin (0.3, 29 and 30 microM
      respectively) using CDNB as a substrate. When ethacrynic acid (for GST P1-1),
      CuOOH (for A1-1) and 1,3-bis (2-chloroethyl)-1-nitrosourea (for GST M1-1) were
      used as substrates, these compounds did not significantly inhibit the GST
      isoforms. However, progesterone was a potent inhibitor of GST P1-1 (IC50 = 1.4
      microM) with ethacrynic acid as substrate. These results suggest that the target
      of chemomodulators in vivo could be a specific resistance-related protein.

PMID- 17194032
TI  - The extract of leaves of Acer truncatum Bunge: A natural inhibitor of fatty acid
      synthase with antitumor activity.
AB  - Fatty acid synthase (FAS) has been identified as a potential antitumor target.
      The extract from the leaves of Acer truncatum Bunge (Extr) was prepared to assay
      its inhibitory activity against FAS, which was isolated from duck liver, and the
      correlated antitumor bioactivity. Its inhibition of FAS is composed of reversible
      fast-binding inhibition, IC50 = 0.7 microg/ml, and irreversible slow-binding
      inhibition following saturation kinetics with a dissociation constant of 0.68
      microg/ml and a limiting rate constant of 0.0288 min(-1). The Extr exhibited
      different type of inhibitions against the three substrates in the FAS overall
      reaction. Compared with EGCG in inhibition constant and IC50 value, the Extr
      appeared to be a more efficient inhibitor, and exhibited a considerable
      inhibition against the growth of four kinds of cancer cells (patent application
      number 200510068054.2). It was infered that the inhibitory activity is likely
      attributable to the co-operative effect of the components.

PMID- 17194033
TI  - A new fermentation process allows large-scale production of tetra-N-acetyl
      chitotetraosyl allosamizoline.
AB  - A new compound 2, possessing a tetra-N-acetyl-chitotetraosyl moiety as a
      constituent, was synthesized by bacterial fermentation, which used allosamizoline
      1 as the initial acceptor. A 2-binding chitinase assay, indicated that the
      chitinase was inactivated by 2 with IC50 = 0.03 microg/mL.

PMID- 17194034
TI  - Quantitative structure-activity relationship study of new potent and selective
      antagonists at the 5-HT(1A) and adrenergic alpha(1d) receptors: Derivatives of
      spiroethyl phenyl(substituted)piperazine.
AB  - The antagonistic activities of derivatives of spiroethyl
      phenyl(substituted)piperazine at the 5-HT(1A) and adrenergic alpha(1d) receptors
      is quantitatively analyzed employing physicochemical and structural parameters.
      The derived correlation equation revealed that a substituent, other than 2-CH3 in
      the phenyl ring, having higher molar refraction, MR, and a substituent producing
      higher positive field effect at the 3-position are beneficial in increasing the
      binding affinity at the 5-HT(1A) receptor. In addition, a less hydrophobic
      substituent at the 4-position is also helpful in augmenting the binding affinity.
      The 5-R substituents which have higher MR values, however, elicit a detrimental
      effect. Two disubstituted compounds which are not present in the original data
      set and have higher theoretical binding affinities are designed from the
      correlation equation. These compounds consisting of 2-OCH(CH3)2, 3-Cl and 2-C3H7,
      3-Cl in the phenyl ring, have theoretical pK(i) values 10.57 and 10.12
      respectively. For the adrenergic alpha(1d) receptor, a less bulky group at the 3
      position with 5-Cl (or simply a 3-Cl) is advantageous in increasing the binding
      affinity. Likewise, a substituent exhibiting a less negative resonance effect at
      the 4-position and the substituent with low polarizability and showing more a
      negative resonance effect at the 5-position are suitable for enhancement of the
      binding affinity. The analysis provides the grounds for rationalizing substituent
      selection in designing better potency antagonists in the series.

PMID- 17194035
TI  - A quantitative structure-activity relationship study for structurally diverse HIV
      1 protease inhibitors: Contribution of conformational flexibility to inhibitory
      activity.
AB  - In this study, we investigated by linear regression model the SAR data of the 15
      HIV-1 protease inhibitors possessing structurally diverse scaffolds. First, a
      regression model was developed only using the enzyme-inhibitor interaction energy
      as a term of the model, but did not provide a good correlation with the
      inhibitory activity (R2 = 0.580 and Q2 = 0.500). Then, we focused on the
      conformational flexibility of the inhibitors which may represent the diversity of
      the inhibitors, and added two conformational parameters into the model,
      respectively: the number of rotatable bonds of ligands (deltaSrot) and the
      distortion energy of ligands (deltaElig). The regression model by adding
      deltaElig successfully improved the quality of the model (R2 = 0.771 and Q2 =
      0.713) while the model with deltaSrot was unsuccessful. The prediction for a
      training inhibitor by the deltaElig model also showed good agreement with
      experimental activity. These results suggest that the conformational flexibility
      of HIV-1 protease inhibitors directly contributes to the enzyme inhibition.

PMID- 17194036
TI  - The patient, the drug and the kidney.
AB  - Recent policy changes have focused attention on the prevalence of chronic kidney
      disease (CKD) in the UK. In particular, automatic reporting of estimated
      glomerular filtration rate (e-GFR) is a requirement of the National Service
      Framework (NSF) for Renal Services in England. Also, the Quality and Outcomes
      Framework (QOF) of the UK General Medical Services (GMS) Contract (revised in
      April 2006) requires GPs to keep a renal register of patients with CKD with e
      GFRs below 60 mL/min/1.73 m2. Prescribers managing such patients are faced with
      difficult decisions about starting or continuing treatment with drugs that are
      handled by, or potentially toxic to, the kidney. Here we review methods of
      identifying and classifying CKD in adults and the implications of CKD for
      patients' health. We also offer advice on prescribing for these patients while
      minimising the risks of drug-related renal toxicity. We do not aim to give
      detailed guidance on every drug, but rather to highlight general principles of
      drug therapy and key sources of information and advice.

PMID- 17194037
TI  - Diagnosis and management of knee injuries.

PMID- 17194038
TI  - Putting the spotlight on ankylosing spondylitis.

PMID- 17194039
TI  - Growing pains: making an accurate diagnosis.

PMID- 17194041
TI  - Advances in the treatment of salivary gland disease.

PMID- 17194040
TI  - Recognising polymyalgia rheumatica.

PMID- 17194042
TI  - Tips for tackling the MCQ paper.

PMID- 17194043
TI  - Penile problems.

PMID- 17194045
TI  - Digital documentation.

PMID- 17194046
TI  - Quality assurance and quality enhancement by use of digital clinical
      documentation.
AB  - Clinical documentation, including medical/dental history, oral status findings,
      treatment planning, and progress notes, are prerequisites for the use of
      retrospective evaluation procedures as well as for quality assessment and
      enhancement. A substantial condition for making full profit of these advantages
      of digital clinical records is that their design is based on established
      physiologic- and cognitive-ergonomic concepts.

PMID- 17194048
TI  - Ubiquitous computing in shared-care environments.
AB  - In light of future challenges, such as growing numbers of elderly, increase in
      chronic diseases, insufficient health care budgets and problems with staff
      recruitment for the health-care sector, information and communication technology
      (ICT) becomes a possible means to meet these challenges. Organizational changes
      such as the decentralization of the health-care system lead to a shift from in
      hospital to both advanced and basic home health care. Advanced medical
      technologies provide solutions for distant home care in form of specialist
      consultations and home monitoring. Furthermore, the shift towards home health
      care will increase mobile work and the establishment of shared care teams which
      require ICT-based solutions that support ubiquitous information access and
      cooperative work. Clinical documentation and decision support systems are the
      main ICT-based solutions of interest in the context of ubiquitous computing for
      shared care environments. This paper therefore describes the prerequisites for
      clinical documentation and decision support at the point of care, the impact of
      mobility on the documentation process, and how the introduction of ICT-based
      solutions will influence organizations and people. Furthermore, the role of
      dentistry in shared-care environments is discussed and illustrated in the form of
      a future scenario.

PMID- 17194047
TI  - Podcasts--an emerging form of digital publishing.
AB  - Podcasting has recently emerged as an important information technology tool for
      health professionals and consumers around the world. Prestigious journals,
      international conferences, universities and government agencies among other
      entities are starting to publish digital informotion via audio and video
      podcasts. Podcosting is distinguished from other forms of digital audio-video
      content because it can be subscribed to (using Real Simple Syndication or RSS)
      and easily accessed from a personal computer. Further, it can be downloaded to a
      mobile device, such as an iPod where the user is able to listen to or watch it
      anywhere, anytime. Podcosting is used in new and evolving ways to publish
      information for healthcare education, patient care, professional continuing
      education, and in support of healthcare research. In addition to a description of
      what podcasting is, how podcasts are created, and how they are used, this paper
      addresses four critical issues that are emerging concerning podcasts. These
      issues are intellectual property and copyright, podcast preservation, podcast
      location, and podcast standards. As podcasting matures and new uses are
      discovered, we will see podcasting incorporated into our education, research and
      patient care publication paradigm.

PMID- 17194049
TI  - Theoretical models in dentistry.
AB  - For the exchange between science and practice, a language that is as precise as
      possible is also required in dentisty. This language is necessarily based on our
      ideas about the relationships in reality. Since standardization is unavoidable,
      various methods have been developed in informatics as to how these models can be
      represented and made more precise. On this basis, it is possible to neutrally
      discuss the situations in which a given form of treatment is expedient or not. A
      step-by-step approach to standardization of dental language with the aid of meta
      models is shown by reference to examples. The medrapid.info service is presented
      as on approach to making medical and dental language more precise.

PMID- 17194050
TI  - An object-relational model for structured representation of medical knowledge.
AB  - Domain specific knowledge is often not static but continuously evolving. This is
      especially true for the medical domain. Furthermore, the lack of standardized
      structures for presenting knowledge makes it difficult or often impossible to
      assess new knowledge in the context of existing knowledge. Possibilities to
      compare knowledge easily and directly are often not given. It is therefore of
      utmost importance to create a model that allows for comparability, consistency
      and quality assurance of medical knowledge in specific work situations. For this
      purpose, we have designed on object-relational model based on structured
      knowledge elements that are dynamically reusable by different multi-media-based
      tools for case-based documentation, disease course simulation, and decision
      support. With this model, high-level components, such as patient case reports or
      simulations of the course of a disease, and low-level components (e.g.,
      diagnoses, symptoms or treatments) as well as the relationships between these
      components are modeled. The resulting schema has been implemented in AMOS II, on
      object-relational multi-database system supporting different views with regard to
      search and analysis depending on different work situations.

PMID- 17194051
TI  - Computer-assisted learning and simulation systems in dentistry--a challenge to
      society.
AB  - INTRODUCTION: Computer technology is increasingly used in practical training at
      universities. However, in spite of their potential, computer-assisted learning
      (CAL) and computer-assisted simulation (CAS) systems still appear to be
      underutilized in dental education. MATERIALS AND METHODS: Advantages, challenges,
      problems, and solutions of computer-assisted learning and simulation in dentistry
      are discussed by means of MEDLINE, open Internet platform searches, and key
      results of a study among German dental schools. RESULTS: The advantages of
      computer-assisted learning are seen for example in self-paced and self-directed
      learning and increased motivation. It is useful for both objective theoretical
      and practical tests and for training students to handle complex cases. CAL can
      lead to more structured learning and can support training in evidence-based
      decision-making. The reasons for the still relatively rare implementation of
      CAL/CAS systems in dental education include an inability to finance, lack of
      studies of CAL/CAS, and too much effort required to integrate CAL/CAS systems
      into the curriculum. CONCLUSION: To overcome the reasons for the relative low
      degree of computer technology use, we should strive for multicenter research and
      development projects monitored by the appropriate national and international
      scientific societies, so that the potential of computer technology can be fully
      realized in graduate, postgraduate, and continuing dental education.

PMID- 17194052
TI  - Linking case management and community development.
AB  - Case management, in various forms, is now institutionalized as a core part of
      policy and programs designed to deliver home- and community-based services to
      older adults. The case management role, in theory, requires attention to both
      client and system goals, although in practice the system goals that have received
      most attention have been gatekeeping and resource allocation. While case managers
      have been admonished to find and develop resources in the community, this has
      primarily taken the form of including informal services in individual client care
      plans. What has been missing is focused attention to the potential of the
      community as a nurturing environment with the capacity to support older adults
      and their caregivers. Sustainable care for older adults cannot be achieved by
      formal service and family support alone. This article proposes the creation of
      linkages between case managers, who build the service arrangements for older
      people, and community developers, who are responsible for building community
      capacity and social capital. It is argued that this linkage is essential for
      establishing the foundations of a caring community with the capacity to support
      older people.

PMID- 17194053
TI  - Care managers' time use: differences between community mental health and older
      people's services in the United Kingdom.
AB  - Since the community care reforms of the early 1990s, care management in the
      United Kingdom has become the usual means of arranging services for even the most
      straightforward of social care needs. This paper presents data from a diary study
      of care managers' time use, from a sample of social services commissioning
      organizations representing the most common forms of care management practiced in
      England at the end of the 20th century. It compares the working practices of care
      managers in community mental health service settings to the practices of those
      situated in older people's services. Evidence is provided to suggest that while
      the former follow a more clinical model of care management, those working with
      older people take an almost exclusively administrative approach to their work. In
      addition, the multidisciplinary nature of mental health service teams appears to
      facilitate a more integrated health and social care approach to care management
      compared to the approach to older people's services. Further enquiry is needed as
      to the comparative effectiveness of these different modes of working in each
      service setting.

PMID- 17194054
TI  - Client satisfaction with rural substance abuse case management services.
AB  - Although many substance abuse organizations offer case management services,
      little is known about clients' satisfaction as consumers of case management
      services. The purpose of this study was to evaluate consumer preferences
      regarding the delivery of case management services in a rural substance abuse
      treatment program. For this study, 120 clients (30 in each of four research
      conditions) were interviewed about their experiences in the Iowa Case Management
      Project (ICMP), a field-based clinical trial evaluating a strengths-based model
      of case management for rural clients in drug abuse treatment. A mixed-method
      approach evaluated clients' responses from a semistructured interview. Most
      clients preferred meeting with their case manager in their own home. Clients also
      stated that they preferred specific characteristics of case management services
      namely, convenience, privacy, comfort, and accessibility. Finally, clients wanted
      more time with their case managers over time. Although clients in drug treatment
      are not often considered as consumers, we found that client satisfaction with
      case management services could be studied and that clients appreciated being
      asked about their experiences. By targeting perceived and actual barriers to
      meeting with case managers (e.g., availability of transportation), service
      utilization by clients may be increased along with overall satisfaction.

PMID- 17194055
TI  - Caring for an adult child with cognitive disabilities: meeting the dual needs of
      an adult and child.
AB  - A significant proportion of families in the United States provide care for an
      adult child who has a cognitive impairment. Significant issues may arise in the
      context of providing this care, including medical concerns, the nature of the
      relationship between the adult cognitively impaired child and his or her parents,
      safety concerns in the home, difficulties that the adult child may face in the
      community, and employment-related issues. We focus, as well on the need to plan
      for the future through the execution of powers of attorney, living wills, and
      accessing government benefits for the individual Caregiver stress is also a
      concern. We provide various alternatives for the management of these issues.

PMID- 17194056
TI  - Cash and counseling: a promising option for consumer direction of home- and
      community-based services and supports.
AB  - The Cash and Counseling Demonstration began as a 3-state social experiment to
      test the claims of members of the disability community that, if they had more
      control over their services, their lives would improve and costs would be no
      higher. The 2004 expansion to 12 states brings us closer to the tipping point
      when this option will be broadly available. The original demonstration was a
      controlled experiment with randomized assignment, supplemented by an ethnographic
      study and a process evaluation. Consumers managing flexible, individualized
      budgets were much more satisfied, had fewer unmet needs, and had comparable
      health outcomes. Access to service and supports was greatly improved. Consumer
      direction is increasingly accepted as a desirable option in home and community
      services.

PMID- 17194058
TI  - Urinary incontinence evaluation and the utility of pessaries in older women.
AB  - Urinary incontinence and pelvic organ prolapse are common conditions affecting
      the elderly. A careful evaluation of urinary incontinence, including history and
      physical examination, will often determine the etiology of this condition.
      Vaginal pessaries are a safe and efective treatment for both urinary incontinence
      and pelvic organ prolapse. They should be considered a viable alternative to
      surgery especially in the elderly with complicated medical histories. This
      article reviews the etiology of urinary incontinence, offers a guide in the
      evaluation of the incontinent woman, and reviews the use of pessaries for the
      treatment of incontinence and pelvic organ prolapse.

PMID- 17194057
TI  - Power, family, and filial responsibility related to elder care in rural Japan.
AB  - This article explores the discourse on filial responsibility as it intersects
      with familial roles and power relationships as represented by women living in
      rural Japan. Using case studies, I consider some of the intergenerational and
      intragenerational issues that arise as Japanese women contemplate or attempt to
      cope with care of elder parents and consider the manner in which the concept of
      filial piety, or filial responsibility, is expressed and conceptualized in
      relation to these issues. I argue that many continue to think about elder care in
      ways that emphasize the responsibility of children to care for their parents, but
      that the discourse on filial piety is continually constructed and reconstructed
      as people provide and contest roles associated with elder care, both from the
      perspective of the child and from that of the parents. To explore these issues, I
      consider the cases of two women who were facing issues related to provision of
      care to elder parents and who structured these in terms of notions about filial
      responsibility. The cases were obtained during extended fieldwork in an
      agricultural community in northern Japan.

PMID- 17194059
TI  - Overweight and at-risk for overweight among Hawai'i public school students
      entering kindergarten, 2002-2003.
AB  - Recent studies have pointed to an increasing problem of overweight and obesity in
      children in Hawai'i, but all of these studies have been conducted in specific
      communities or special population groups. No broad population-based studies have
      been conducted to document the extent of overweight in the general population of
      children in Hawai'i. To provide a population based estimate of overweight in
      Hawai'i's children, this study examined Student Health Records for 10, 199
      children entering kindergarten in public schools during 2002-2003. Data on age,
      gender, height, and weight were used to calculate BMI (body mass index) scores.
      Because records for all students entering public school kindergarten were
      available for analysis, the data presented here represents the broadest estimates
      of overweight and at risk for overweight in Hawai'i's children published to date.
      The results illustrate that almost one-third of the children aged 4-6 years old
      entering Hawai'i public schools are either overweight or at risk for overweight.
      Rates are higher in rural school complexes than urban ones. Compared to a 1984
      study that found 'no significant under or over nutrition' in Hawai'i's school
      children, our results suggest that almost one-third of children aged 4-6 entering
      Hawai'i public schools are either overweight or at risk for overweight.
      Physicians should be aware of this growing problem, and seek to implement
      practices to combat overweight among their pediatric patients and families.

PMID- 17194060
TI  - Conjugate heptavalent pneumococcal vaccine outcome improvements.
AB  - Heptavalent conjugate pneumococcal vaccine (PCV7) is now routinely administered
      to infants. Medical records from a pediatric outpatient clinic were used to
      identify two study groups: 1) those born between January 1995-May 1997(controls),
      2) those born between April 2000--May 2001 (PCV7 group). The PCV7 group showed a
      lower incidence of otitis media episodes, clinic visits for fever and respiratory
      symptoms, antibiotic prescriptions, ceftriaxone use, and hospitalizations
      (singled sided probabilities).

PMID- 17194062
TI  - Do Japanese have an increased susceptibility to colorectal cancer?

PMID- 17194061
TI  - Oral antibiotic treatment for methicillin-resistant Staphylococcus aureus skin
      and soft tissue infections: review of the literature.
AB  - BACKGROUND: The emergence of methicillin-resistant Staphylococcus aureus (MRSA)
      as a cause of hospital- and community-associated infection has been reported
      worldwide and has become an increasing health care problem. Treatment options for
      MRSA infection are limited, complicated and expensive. Oral antibiotics have been
      used in the outpatient setting for less severe MRSA infections such as skin and
      soft tissue infections (SSTIs), but their efficacy has not been well studied.
      METHODS: We reviewed the literature and Internet information sources as well as
      recent abstracts for factors relevant to the in-vitro and in-vivo activity and
      adverse effects of oral antibiotics of possible value in treating MRSA SSTI.
      RESULTS: Most of MRSA isolates are still susceptible to linezolid, TMP-SMX, and
      the tetracyclines but less susceptible to the quinolones, clindamycin, and
      erythromycin. Only the quinolones have bactericidal activity, which may be a
      relevant factor if there is bacteremia. In-vivo studies indicate a high clinical
      cure rate with linezolid, TMP-SMX, doxycycline and minocycline. Adverse effects
      are different among the drugs and are a significant factor. Antibiotics with once
      daily dosing such as the quinolones have advantage in regard to compliance.
      Linezolid has the highest daily cost of treatment whereas the cost of the
      tetracyclines, erythromycin, and TMP-SMX is much lower. CONCLUSION: The
      antibiotics available for MRSA SSTI vary widely in chances of resistance,
      activity, adverse effects, and cost. More clinical studies of clinical efficacy
      are needed, especially with comparative trials. Selection of the most appropriate
      antibiotic will depend upon local antibiotic resistance, type of infection,
      potential adverse effects, and cost for the individual.

PMID- 17194063
TI  - Issues in medical malpractice IV.

PMID- 17194064
TI  - Presentations and conferences: can we measure their value?

PMID- 17194065
TI  - Caries prevalence in 12-year-old children from Germany. Results of the 2004
      national survey.
AB  - OBJECTIVE: To determine the prevalence of dental caries in 12-year-old children
      in all 16 German Federal States in 2004 as part of a longitudinal observation
      project. DESIGN: A cross-sectional oral health survey of children 12 years of age
      was performed in 2004. SUBJECTS: After random selection 43,950 children were
      examined in schools. METHOD: DMFT and fissure sealants were recorded following
      WHO criteria. Caries was diagnosed at the caries into dentine threshold (D3)
      using the visual method without radiography or fibre-optic transillumination.
      RESULTS: The proportion of children with caries experience was 39.3% throughout
      Germany. The mean DMFT score was 0.98 and the average Significant Caries Index
      (SiC) was 2.72. Compared to the results obtained in 2000, caries prevalence and
      caries experience decreased in this age group. As in 2000, all these specific
      results showed a wide variation among the different federal states, i.e., mean
      regional DMFT values between 0.71 and 1.42 were found and the mean number of
      fissure sealed teeth ranged between 1.9 and 3.4. CONCLUSION: The decrease in
      caries prevalence observed between 1994 and 2000 continued between 2000 and 2004,
      although once again considerable inequalities in oral health between the various
      federal states were observed.

PMID- 17194066
TI  - The relationship between prevalence and incidence of dental caries. Some
      observational consequences.
AB  - To investigate the relationship between incidence and prevalence of caries. The
      principles are illustrated by means of Lexis diagrams, which show the
      relationship between cases of caries belonging to a population with a certain
      incidence and natural course of the disease in time. The analysis shows how
      studies on prevalence yield associations that reflect the determinants of the
      disease progression just as much as the causes of disease. Also the diagnostic
      criteria of the disease affect the prevalence estimate. The presence of fluoride
      changes the course of the disease and the prevalence estimate even with an
      unchanged incidence rate. This knowledge about incidence and prevalence should be
      taken into consideration when data from cross-sectional and time-series studies
      are interpreted. In an example from Norway the prevalence of caries was reduced.
      During the same period fluoride was made universally available, invasive
      treatment criteria were changed to less invasive and the time between the regular
      examinations were extended. These factors affect the estimates of caries made by
      cross-sectional recordings.

PMID- 17194067
TI  - Characteristics attributed to individuals with dental fluorosis.
AB  - BACKGROUND: Previous investigations of the public perception of dental fluorosis
      have focused mainly on aesthetics. Other characteristics which could potentially
      be ascribed to fluorosis, such as perceived personality traits, have not been
      examined. OBJECTIVES: This study aimed to identify personal characteristics
      (descriptors) attributed to people with fluorosis of varying degrees of severity,
      as depicted in standardised photographs viewed from different perspectives.
      METHOD: Extra-oral (full face) and intra-oral images of male and female subjects
      were digitally manipulated to represent normal dental enamel, mild, moderate, and
      severe fluorosis. The images were then scored by 90 members of the public (45M,
      45F), under different experimental conditions, which varied the level of cueing
      to the teeth. Participants were asked (i) to record their spontaneous
      descriptors, (ii) select relevant descriptors from a predefined list of 50
      descriptors and traits. RESULTS: 170 different word or phrase descriptors were
      spontaneously attributed to the images. Characteristics used to describe
      fluorosis varied with the degree of severity. However, endorsements were
      significantly influenced by whether participants viewed extra or intraoral images
      and the degree of cueing. Conditions which most accurately mirrored everyday
      social interactions, that is viewing extraoral images without cueing to pay
      particular attention to the mouth, were least likely to result in the attribution
      of characteristics that varied with levels of fluorosis. CONCLUSIONS: While
      characteristics varying with severity of dental fluorosis were ascribed, more
      sophisticated attitudinal measures are required to ascertain the wider social
      impact of fluorosis beyond the aesthetic.

PMID- 17194068
TI  - DIAGNOdent--an adjunctive diagnostic method for caries diagnosis in epidemiology.
AB  - The DIAGNOdent system is intended as an aid to caries detection and has undergone
      extensive investigation in experimental and clinical studies. Its applicability
      for epidemiological purposes has yet to be evaluated. The Objective of the
      present study was to evaluate the DIAGNOdent system under field conditions. BASIC
      RESEARCH DESIGN: The subjects comprised a sub-sample from an on-going
      epidemiological study. PARTICIPANTS AND CLINICAL SETTING: In 39 individuals, 97
      sites were visually identified as possibly carious: 42 occlusal, 13 lingual, 19
      buccal and 23 approximal sites. MAIN OUTCOME MEASURES: Three DIAGNOdent
      measurements were taken at each site under varying conditions: (1) naturally wet,
      (2) dried, and (3) polished and dried surfaces. Three sets of measurements were
      obtained and compared by intra-class correlation and paired sample t-tests.
      RESULTS: All correlation coefficients were > 0.9. There was a systematic
      difference between mean scores from naturally wet sites (without cleaning) and
      from either dried, or polished and dried sites. The difference was marginal and
      did not impact on the threshold for recording sites as carious. In two subjects,
      high unexpected values were recorded on sound sites prior to actual measurements,
      i.e. during establishment of a standard value for a sound site. The overall
      findings were not affected by these values, as they were consistently high in all
      three measurements. CONCLUSIONS: The DIAGNOdent system performed satisfactorily
      under different measurement conditions. The present study indicates that the
      DIAGNOdent system would be applicable in field studies, provided consistent study
      conditions are maintained and unexpected values are interpreted with caution.

PMID- 17194070
TI  - Performance indicators used to assess the quality of primary dental care.
AB  - An appropriate quality of medical care including dental care should be an
      objective of every government that aims to improve the oral health of its
      population. OBJECTIVES: To determine performance indicators that could be used to
      assess the quality of primary dental care at different levels of a health care
      system, the sources for data collection and finally, the dimensions of quality
      measured by these indicators. METHOD: An explorative study of the international
      literature was conducted using medical databases, journals and books, and
      official websites of organisations and associations. RESULTS: This resulted in a
      set of 57 indicators, which were classified into the following dimensions for
      each intended user group: For patients: health outcomes and subjective
      indicators; for professionals: their performance and the rates of success,
      failure and complications; for health care system managers and policymakers:
      their resources, finances and health care utilisation. CONCLUSION: A set of 57
      performance indicators were identified to assess the quality of primary dental
      care at the levels of patients, professionals and the health care system. These
      indicators could be used by managers and decision-makers at any level of the
      health care system according to the characteristics of the services.

PMID- 17194069
TI  - Prevalence and factors associated with traumatic dental injuries (TDI) to
      anterior teeth of 11-13 year old Thai children.
AB  - OBJECTIVE: The objective was to assess the prevalence and factors associated with
      Traumatic Dental Injuries (TDI) to anterior teeth of 11-13 year old Thai
      children. METHODS: A cross sectional survey was carried out in a sample of 2,725
      children from 52 primary school classes in the Chiang Mai urban area of Thailand.
      The children were clinically examined for TDI and interviewed. RESULTS: 35.0% of
      children experienced TDI. Males (45.3%) had TDI levels approximately twice as
      high as females (25.2%), and the prevalence of TDI increased with age. TDI were
      more common amongst children living in more disadvantaged households and whose
      parents were less educated. Children with an overjet greater than 5mm were also
      more likely to have TDI. Most of the affected children (20.6%) had trauma to I
      tooth, 10.3% to 2, 2.6% had 3 teeth affected. The proportion of damaged teeth was
      4.6 per 100 anterior teeth. Central incisors were the most common teeth with TDI,
      both in the upper and lower jaws. Enamel fracture was the major type of TDI. Most
      of the TDI occurred at home and school. Running was the major activity leading to
      TDI. 'Falls' was the most common manner causing TDI (24.8%). Ground surfaces
      (22.4% of all cases), particularly concrete surfaces (14.6% of all cases), were
      the most common vectors which directly contacted or injured children. Biting hard
      material was the most common activity leading to TDI. CONCLUSION: Traumatic
      dental injuries are common and are an important dental public health problem in
      Thailand.

PMID- 17194071
TI  - A survey of school dental screening practise in community dental services of
      England and Wales in 2003.
AB  - OBJECTIVE: To describe the school dental screening process in Community Dental
      Services across England and Wales. BASIC RESEARCH DESIGN: Cross-sectional study
      using a postal questionnaire. CLINICAL SETTING: Community Dental Services.
      PARTICIPANTS: Clinical Directors of Community Dental Services in England and
      Wales. MAIN OUTCOME MEASURES: Respondents answers about the objectives of school
      dental screening, criteria used for referring a child, methods of informing
      parents of screening results, and methods used to confirm subsequent dental
      attendance. RESULTS: The response rate for this study was 92.1%. Respondents
      identified dental registration (75.2%) and attendance at a dentist (82.9%) as
      objectives of school dental screening. Less than one third (29.5%) saw the
      activity as having a preventive role. Caries in the primary and secondary
      dentitions and soft tissue lesions were reported as key criteria for referral.
      Methods of follow-up of screened positive children differed and were often
      inadequate; approximately one third of respondents used a letter carried home by
      the child that did not allow parents to inform the CDS of action taken. Half of
      the respondents routinely collected data on the number of screened positive
      children who subsequently visit a dentist. CONCLUSIONS: School dental screening
      is delivered in a similar fashion throughout England and Wales but methods of
      informing parents of a positive screen and follow-up mechanisms for children with
      positive screens vary. Most school dental screening programmes do not collect
      sufficient data to evaluate the impact of their programmes on children's oral
      health.

PMID- 17194072
TI  - The prevalence and pattern of hypodontia of the permanent teeth and crown size
      and shape deformity affecting upper lateral incisors in a sample of Jordanian
      dental patients.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence and pattern of
      hypodontia and the extent of congenital malformation in the permanent teeth of a
      sample of Jordanian adults. MATERIAL AND METHODS: Clinical examinations were
      carried out on 1045 dental patients aged 16 to 45 years to record any congenital
      absence of teeth except 3rd molars and to note any crown shape or size
      deformities affecting the upper lateral incisor. The congenital absence of
      permanent teeth was confirmed by taking complete dental history and
      orthopantomograms. Impacted teeth and teeth lost as a consequence of extraction
      or trauma were recorded as present. RESULTS: The prevalence of hypodontia was
      found to be 5.5% of the sample and the lower second premolar was the most
      frequently missing tooth. The number of missing upper lateral incisors was
      significantly higher than that of lower lateral incisors, (p < 0.05). Peg-shaped
      and reduced size upper lateral incisors were observed in 2.3% and 2.9% of the
      sample respectively. There were no significant differences according to gender,
      location of tooth according to arch or side of the jaw and hypodontic pattern.
      CONCLUSION: The prevalence of hypodontia was 5.5%, that of peg-shaped lateral
      incisor was 2.3% and that of reduced crown size was 2.9%.

PMID- 17194073
TI  - Relationship between dental caries experience (DMFS) and dental fluorosis in 12
      year-old Puerto Ricans.
AB  - OBJECTIVES: Examine the relationship between (1) DMFS and community fluorosis
      index (CFI) scores, and (2) between individual DMFS and NIDR/Dean Index fluorosis
      scores. DESIGN: Population-based, cross-sectional study. SETTING: Public and
      private schools of Puerto Rico. SUBJECTS: 1435, 12-year old students. METHOD: A
      probabilistic stratified sample was selected from 11 regions of Puerto Rico,
      according to type of school (public and private), and setting (urban and rural).
      Children were examined using NIDR criteria for DMFS and fluorosis. Regressions
      examined the relationship between DMFS means and CFI scores. Individual level
      DMFS was regressed on NIDR/Dean Index scores to test for linear and deviation
      from linear trends. RESULTS: (1) There was no statistically significant
      relationship between regional DMFS and CFI scores, and (2) individual level
      fluorosis scores when dichotomized as 0-2 as the referent level to level 3-4
      demonstrated a statistical significant higher DMFS with the higher fluorosis
      level. Gender and school setting were statistically significant in all models:
      females and public school attendance were associated with increased DMFS.
      CONCLUSION: No ecological relationship between CFI and DMFS scores was found in
      12-year-old children in Puerto Rico. Moderate and severe fluorosis were
      associated with higher DMFS levels relative to lower fluorosis scores, though
      this finding may be associated with restorations placed for cosmetic reasons.
      While controlling severe fluorosis is desirable, this will have little impact on
      overall high caries in Puerto Rican children. These findings suggest caution when
      interpreting caries experience using the DMFS index in populations with differing
      fluorosis levels.

PMID- 17194074
TI  - Prevalence of dental caries in obese and normal-weight Brazilian adolescents
      attending state and private schools.
AB  - OBJECTIVE: To measure the association between dental caries and obesity in
      adolescents aged 12 to 15 years attending state and private schools. BASIC
      RESEARCH DESIGN: Cross-sectional study. RESEARCH SETTING: State and private
      schools in the state of Paraiba, Brazil. PARTICIPANTS: 1665 obese and 1665 normal
      weight adolescents. MAIN OUTCOME MEASURES: These were chosen by means of an
      anthropometric study using height/age and weight/height indices, adopting as
      baseline the National Center for Health Statistics indices. The diagnostic
      criteria for caries were those of the World Health Organization (1997). RESULTS:
      The average DMFT for obese adolescents from state schools was 4.27 and for those
      of normal weight it was 4.25 (p = 0.7802). In private schools, the corresponding
      figures were 1.90 and 1.91, respectively (p = 0.1151). In state schools, the
      caries prevalence amongst the obese group was 50.9% and amongst those of normal
      weight, 52.4% (p = 0.5393). In private schools, it was 9.0% amongst the obese
      group and 9.6% amongst those of normal weight (p 0.6790). CONCLUSIONS: There was
      no statistically significant association between dental caries and obesity.
      Caries levels were higher amongst adolescents attending state schools.

PMID- 17194077
TI  - Interconversion of carbon sites in boat-chair-boat cyclodecane; conformations of
      chlorocyclodecane and cyclodecyl acetate.
AB  - Interconversion of carbon sites in boat-chair-boat (BCB) cyclodecane occurs by
      way of the twist-boat-chair (TBC) conformation, which predicts that C-1 exchanges
      with C-4, etc. The previously obtained low-temperature 13C spectra could be
      matched by assuming (1,4) or (1,3) exchange, but not (1,2) exchange. A free
      energy barrier of 5.54 kcal/mol was obtained for conversion of BCB to TBC at 
      137.4 degrees C. The major conformation of chlorocyclodecane and cyclodecyl
      acetate is assigned to the IIIe BCB.

PMID- 17194076
TI  - [4 + 2]-annulations of chiral organosilanes: Application to the total synthesis
      of leucascandrolide A.
AB  - Complete details of an asymmetric synthesis of leucascandrolide A (1) are
      described. The synthesis highlights the use of two diastereoselective [4 + 2]
      annulations for the assembly of the functionalized bispyranyl macrolide 3. An
      efficient assembly and union of the oxazole-containing side chain 4 with
      macrolide 3 was carried out using a Mitsunobu reaction. A convergent route to the
      oxazole side chain was developed using a Sonogashira cross-coupling between 2
      trifloyloxazole 16 and alkyne 17, which allowed for the installation of the C9'
      C10' (Z)-olefin.

PMID- 17194079
TI  - Mechanism for the regioselective asymmetric addition of grignard reagents to
      malimides: A computational exploration.
AB  - We present a systematic theoretical investigation on the addition reaction of
      Grignard reagents to malimides to understand its mechanism as well as the origin
      of its regio- and diastereo-selectivity. The computations carried out at a hybrid
      density functional B3LYP/6-31G* level of theory reveal that (i) the addition of
      Grignard reagents with N,O-dimethylmalimide (1-methyl-3-methoxypyrrolidine-2,5
      dione) occurs regioselectively at the alpha-carbonyl (C1) by passing through a
      cis-alpha-chelated precursor and affords stereoselectively cis-addition product,
      in qualitative agreement with the previous experimental observations; (ii) such
      regioselectivity is ascribed to the preferential chelation of Grignard reagent to
      the alpha-carbonyl (C1) over the coordination to the alpha-carbonyl (C4); (iii)
      its unusual trans-addition, in sharp contrast to the Cram chelation-type
      stereoselectivity for the reaction of aliphatic alpha- or beta-alkoxy carbonyl
      compounds, is due primarily to the rigidity of the five-membered ring skeleton of
      the malimide that favors the formation of the cis-alpha-chelated precursor; and
      (iv) poor regioselectivity is predicted for the reaction of O-TBDMS-protected
      malimide (1-benzyl-3-(tert-butyldimethylsilyloxy)pyrrolidine-2,5-dione) with
      Grignard reagent and can be ascribed to the large steric repulsion of the bulky
      TBDMS group and the electronic effects of the silyl group that remarkably
      destabilizes the alpha-chelated precursors and the corresponding transition
      states.

PMID- 17194078
TI  - Asymmetric reduction and oxidation of aromatic ketones and alcohols using W110A
      secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus.
AB  - An enantioselective asymmetric reduction of phenyl ring-containing prochiral
      ketones to yield the corresponding optically active secondary alcohols was
      achieved with W110A secondary alcohol dehydrogenase from Thermoanaerobacter
      ethanolicus (W110A TESADH) in Tris buffer using 2-propanol (30%, v/v) as
      cosolvent and cosubstrate. This concentration of 2-propanol was crucial not only
      to enhance the solubility of hydrophobic phenyl ring-containing substrates in the
      aqueous reaction medium, but also to shift the equilibrium in the reduction
      direction. The resulting alcohols have S-configuration, in agreement with
      Prelog's rule, in which the nicotinamide-adenine dinucleotide phosphate (NADPH)
      cofactor transfers its pro-R hydride to the re face of the ketone. A series of
      phenyl ring-containing ketones, such as 4-phenyl-2-butanone (1a) and 1-phenyl-1,3
      butadione (2a), were reduced with good to excellent yields and high
      enantioselectivities. On the other hand, 1-phenyl-2-propanone (7a) was reduced
      with lower ee than 2-butanone derivatives. (R)-Alcohols, the anti-Prelog
      products, were obtained by enantiospecific oxidation of (S)-alcohols through
      oxidative kinetic resolution of the rac-alcohols using W110A TESADH in Tris
      buffer/acetone (90:10, v/v).

PMID- 17194080
TI  - Crystal structure and photochemical behavior in solution of the 3'-N-sulfamate
      analogue of thymidylyl(3'-5')thymidine.
AB  - The 3'-N-sulfamate analogue of thymidylyl(3'-5')thymidine (TnsoT, 1) exhibits a
      preference for a C3'-endo conformation in the solution and solid states. Its
      photochemical behavior in solution is compared to that of its natural
      counterpart, thymidylyl(3'-5')thymidine (TpT, 2), to get further insight into the
      significance of the C3'-endo conformation on the photoproduct formation at the
      single-stranded dinucleotide level. Irradiation at 254 nm of 1 led to the same
      type of photoproducts as observed with 2. However, 1 was significantly more
      photoreactive than 2, and accordingly, the initial rate of photoproduct formation
      was enhanced in accordance with its propensity to base stack compared to 2. The
      corresponding quantum yields were determined and showed that the enhancement
      factor (1 compared to 2) is moderate for the cyclobutane pyrimidine dimer (CPD)
      (1.26) and much higher for the (6-4) photoproduct (1.8). These data strongly
      suggest that the CPD and (6-4) photoproduct arise from distinct minor stacked
      conformations.

PMID- 17194081
TI  - Kinetic and thermodynamic stability of acenes: Theoretical study of nucleophilic
      and electrophilic addition.
AB  - To understand the reactivity of acenes, particularly pentacene, the addition of
      HCl and water to acenes was studied for the benzene-nonacene series at the
      B3LYP/6-31G(d) level of theory. Surprisingly, the reactivity of the acenes
      increases along the series up to hexacene and remains constant from hexacene and
      above due to the biradical character of the ground state of higher acenes. While
      the exothermicity of HCl and water additions are very similar, the activation
      barriers for HCl and water additions differ by a constant factor of ca. 27
      kcal/mol. The barrier for the addition of HCl varies from 44 kcal/mol for benzene
      to 16-18 kcal/mol for pentacene-nonacene, whereas the barrier for the addition of
      water varies from 71 kcal/mol for benzene to 43-46 kcal/mol for pentacene
      nonacene. The transition states (TSs) for the addition of water to acenes are
      relatively "late" on the reaction coordinate, compared to the "earlier" TSs for
      the addition of HCl. There is a substantial substituent effect on the energy
      barriers for these reactions. HCl behaves as an electrophile, with rhoHCl (vs rho
      p) = -4.48 and -3.39 for anthracenes and pentacenes, respectively, while water
      behaves as a nucleophile, with rhoHCl (vs rho p) = 2.35 and 1.39 for anthracenes
      and pentacenes, respectively.

PMID- 17194082
TI  - Fluorescence sensing of anions based on inhibition of excited-state
      intramolecular proton transfer.
AB  - Condensation of 2-(2'-aminophenyl)benzoxazole with p-toluenesulfonyl chloride and
      phenyl isocyanate yields two new anion sensors (TABO and PUBO), which can undergo
      excited-state intramolecular proton transfer (ESIPT) upon excitation. For the
      acid receptor TABO, the ESIPT process can be readily disturbed by basic anions
      such as F-, CH3COO-, and H2PO4- by deprotonating the sulfonamide unit, whereas in
      the case of PUBO, a good hydrogen-bonding donor, the ESIPT process is inhibited
      either by the fluoride-induced deprotonation of the urea unit or by the formation
      of a strong CH3COO--urea intermolecular hydrogen bond complex, and these two
      types of inhibition mechanisms consequently result in different ratiometric
      responses. But other anions with less hydrogen-bonding acceptor abilities cannot
      inhibit the ESIPT. Interestingly, the different inhibition abilities of F-,
      CH3COO-, and H2PO4- produce different spectral behaviors in PUBO, so this new
      sensor successfully distinguishes the subtle difference in these three anionic
      substrates of similar basicity and surface charge density.

PMID- 17194083
TI  - Benzimidazole nitrogen-directed, regiocontrolled, lithiation of ferrocenyl- and
      phenyl-N-n-butylbenzimidazoles.
AB  - 2-Ferrocenyl- and 2-phenyl-N-n-butylbenzimidazoles were synthesized to evaluate
      the influence of the benzimidazole functional group upon their directed
      lithiation. The regiochemistry of lithiation was studied, as well as the effect
      of stabilization of the lithiated species by diamine coordination using
      tetramethyl- ethylenediamine and (-)-sparteine. The lithiations were followed by
      reaction with a variety of electrophiles to give the disubstituted 2-ferrocenyl-
      and 2-phenyl-N-n-butylbenzimidazoles compounds. This study showed that despite a
      simple n-butyl function on the benzimidazole, directed lithiation was readily
      achieved with high regiocontrol on the ferrocenyl and phenyl groups. (-)
      Sparteine failed to provide asymmetric induction in the ferrocene system, and its
      inefficiency is explained by intramolecular coordination of the lithiated species
      by the benzimidazole nitrogen, which is preferred over sparteine coordination.

PMID- 17194084
TI  - Aromaticity and Homoaromaticity in Methano[10]annulenes.
AB  - Aromaticity and neutral homoaromaticity have been evaluated in
      methano[10]annulenes systems, 1,4-methano[10]annulene (1), 1,5
      methano[10]annulene (2), and 1,6-methano[10]annulene (3). C-C bond lengths
      indicate that 1 presents higher bond alternation than 2 and 3. The relative
      energies were determined at the B3LYP/6-311+G(d,p) level, and they pointed out
      that 3 is the most stable isomer. Strain energies, evaluated employing
      homodesmotic reactions, show the same order as the relative energies. Through a
      decomposition of strain energies, it could be concluded that the rings absorb
      more tension than the bridges. The changes in aromaticity were evaluated by
      magnetic susceptibilities, chiM, HOMA, NICS, and resonance energies, RE. HOMA,
      RE, and chiM indicate that 2 and 3 are strongly, and 1 is fairly, aromatic. NICS
      does not provide reliable results, due to interference of ring and bridge atoms.
      NBO analysis presents some interactions that suggest the existence of neutral
      homoaromaticity. GPA indices (evaluated at the B3LYP/6-31G* level) point out that
      homoaromaticity plays a relevant role only in 3. Moreover, this work is the first
      in the current literature that studies 1,4-methano[10]annulene (1).

PMID- 17194085
TI  - Systematic structure-property investigations and ion-sensing studies of pyridine
      derivatized donor/acceptor tetrakis(arylethynyl)benzenes.
AB  - Nine structural isomers of a tetrakis(arylethynyl)benzene chromophore
      functionalized with dibutylaniline and pyridine units as respective donors and
      acceptors have been synthesized and their steady-state spectroscopic parameters
      investigated. The effects of small structural variations on the electronic
      absorption and emission spectra have been explored in evaluation of their
      potential as optical materials components. These structural variations have
      predictable consequences and thus allow fine-tuning of the optoelectronic
      properties for specialized applications. Strong solvatochromism is also
      displayed. Their response to protonation and metal ion complexation caused
      dynamic shifts in the emission spectra, providing evidence for a stepwise
      intramolecular charge-transfer switching phenomenon manifested by either
      hypsochromic or bathochromic shifts in the fluorescence lambda max. These shifts
      are believed to correlate strongly to the relative energies of the fluorophore's
      HOMO and LUMO levels. The complete array of compounds represents an interesting
      set of candidates for fluorescent sensing device components.

PMID- 17194087
TI  - Synthesis and fluorescent properties of bi- and tricyclic 4-N
      carbamoyldeoxycytidine derivatives.
AB  - New bi- and tricyclic deoxycytidine derivatives (dChpd, dCmpp, dCtpp, dCppp) were
      synthesized as analogues of a fluorescent nucleoside, dChpp, previously reported.
      The carbamoyl group of dChpd and the 5-position of the cytosine ring are bridged
      via an ethylene linker so that the modified group forms a nonplanar structure
      with the cytosine ring. The fluorescent study of dChpd indicated that the
      coplanar structure between the carbamoyl group and the cytosine ring is of
      importance. N-Methylation of the carbamoyl group (dCmpp) weakened the intensity
      of the fluorescence of dChpp, and the derivative (dCtpp), which had a
      thiocarbamoyl group, lost its fluorescent property. Moreover, addition of a
      pyrrolo-ring (dCppp) to dChpp enhanced the intensity of fluorescence, and an
      emission light was observed with a marked Stokes shift of 120 nm.

PMID- 17194086
TI  - Enantioselective fluorescent recognition of amino alcohols by a chiral
      tetrahydroxyl 1,1'-binaphthyl compound.
AB  - The tetrahydroxyl derivative of BINOL, (S)- or (R)-1, and its analogues are
      synthesized. (S)- or (R)-1 can be used to conduct the enantioselective
      recognition of chiral amino alcohols. In comparison with BINOL, the two
      additional hydroxyl groups of (S)- or (R)-1 have increased the binding of this
      compound with the amino alcohols and significantly improved the fluorescence
      quenching efficiency. The fluorescence responses of (S)- or (R)-1 toward amino
      alcohols are compared with those of its analogues (R)-4 and (R)-6. It shows that
      the interaction of the central naphthyl hydroxyl groups of (S)- or (R)-1 with the
      substrates is responsible for the observed fluorescence quenching, and the two
      additional alkyl hydroxyl groups increase the quenching efficiency.

PMID- 17194088
TI  - Direct cyanation of heteroaromatic compounds mediated by hypervalent iodine(III)
      reagents: In situ generation of PhI(III)-CN species and their cyano transfer.
AB  - Hypervalent iodine(III) reagents mediate the direct cyanating reaction of a wide
      range of electron-rich heteroaromatic compounds such as pyrroles 1, thiophenes 3,
      and indoles 5 under mild conditions (ambient temperature), without the need for
      any prefunctionalization. Commercially available trimethylsilylcyanide is usable
      as a stable and effective cyanide source, and the reaction proceeds in a
      homogeneous system. The N-substituent of pyrroles is crucial to avoid the
      undesired oxidative bipyrrole coupling process, and thus a cyano group was
      introduced selectively at the 2-position of N-tosylpyrroles 1 in good yields
      using the combination of phenyliodine bis(trifluoroacetate) (PIFA), TMSCN, and
      BF3.Et2O at room temperature. In the reaction mechanism, cation radical
      intermediates of heteroaromatic compounds are involved as a result of single
      electron oxidation, and the key to successful transformations seems to depend on
      the oxidation potential of the substrates used. Thus, the reaction was also
      successfully extended to other heteroaromatic compounds having oxidation
      potentials similar to that of N-tosylpyrroles such as thiophenes 3 and indoles 5.
      However, regioisomeric mixtures of the products derived from the reaction at the
      2- and 3-positions were obtained in the case of N-tosylindole 5a. Further
      investigation performed in our laboratory provided insights into the real active
      iodine(III) species during the reaction; the reaction is induced by an active
      hypervalent iodine(III) species having a cyano ligand in situ generated by ligand
      exchange reaction at the iodine(III) center between trifluoroacetoxy group in
      PIFA and TMSCN, and effective cyanide introduction into heteroaromatic compounds
      is achieved by means of the high cyano transfer ability of the hypervalent
      iodine(III)-cyano intermediates. In fact, the reaction of N-tosylpyrrole 1a with
      a hypervalent iodine(III)-cyano compound (e.g., (dicyano)iodobenzene 8), in the
      absence of TMSCN, took place to afford the 2-cyanated product 2a in good yield,
      and an effective preparation of the intermediates is of importance for successful
      transformation. 1,3,5,7-Tetrakis[4-{bis(trifluoroacetoxy)-iodo}phenyl]adamantane
      12, a recyclable hypervalent iodine(III) reagent, was also comparable in the
      cyanating reactions as a valuable alternative to PIFA, affording a high yield of
      the heteroaromatic cyanide by facilitating isolation of the cyanated products
      with a simple workup. Accordingly, after preparing the active hypervalent
      iodine(III)-CN species by premixing of a recyclable reagent 12, TMSCN, and
      BF3.Et2O for 30 min in dichloromethane, reaction of a variety of pyrroles 1 and
      thiophenes 3 provided the desired cyanated products 2 and 4 in high yields. The
      iodine compound 13, recovered by filtration after replacement of the reaction
      solvent to MeOH, could be reused without any loss of activity (the oxidant 12 can
      be obtained nearly quantitatively by reoxidation of 13 using m-CPBA).

PMID- 17194089
TI  - Ethynyl-linked (pyreno)pyrrole-naphthyridine and aniline-naphthyridine molecules
      as fluorescent sensors of guanine via multiple hydrogen bondings.
AB  - New fluorescent molecular sensors for 9-alkylguanines were constructed by
      conjugation of 2-acetamido-1,8-naphthyridine with N-Boc-pyrrole, N-Boc-pyreno[2,1
      b]pyrrole, or acetanilide moieties via an ethynyl bridge. In combination with the
      triple hydrogen-bonding motif of 2-acetamidonaphthyridine toward alkylguanine, an
      additional binding site was provided by the substituent properly located on the
      pyrrole or aniline ring to enhance the affinity of these receptor molecules.
      Besides the ESI-MS analyses, the binding events were readily monitored by the
      absorption and fluorescence changes in the visible region.

PMID- 17194090
TI  - Amino acid mediated intramolecular asymmetric aldol reaction to construct a new
      chiral bicyclic enedione containing a seven-membered ring: remarkable inversion
      of enantioselectivity compared to the six-membered ring example.
AB  - A detailed study to assess the enantioselectivity of the amino acid mediated
      intramolecular asymmetric aldol reaction of 1,3-cycloheptanedione bearing a C-2
      methyl substituent has been undertaken. The cyclizations were mediated by a
      series of l-amino acids in the presence of an acid cocatalyst. Strikingly, the
      process is characterized by an inversion of enantioselectivity when compared to a
      similar reaction involving the 1,3-cyclohexanedione counterpart.

PMID- 17194091
TI  - Stereocomplexity and stereoselective synthesis of triamine molecules bearing four
      chiral carbon centers: Stereodifferentiated preparation of all 10 stereoisomers
      of 2,6-bis[1-(1-phenylethylamino)ethyl]pyridines.
AB  - Compounds (S,S)-2,6-bis(1-hydroxyethyl)pyridine, (R,R)-2,6-bis(1
      acetoxyethyl)pyridine, and (1R,1'S)-2-(1-acetoxyethyl)-6-(1'
      hydroxyethyl)pyridine were obtained by lipase-catalyzed kinetic acetylation of
      2,6-bis(1-hydroxyethyl)pyridine as enantiomerically pure forms. The
      stereospecific replacement of hydroxy groups with (R)-phenylethylamine or (S)
      phenylethylamine via its methanesulfonate or toluenesulfonate simultaneously or
      stepwise afforded all the stereoisomers of 1. Stereospecific preparation of all
      the 10 possible stereoisomers of 2,6-bis[1-(1-phenylethylamino)ethyl]pyridines 1a
      f was achieved. Triamine 1b reacted with ZnCl2 to form Zn-triamine complex 16,
      the structure of which was determined by X-ray crystallographic analysis.

PMID- 17194092
TI  - BF3.Et2O-catalyzed direct carbon-carbon bond formation of alpha-EWG Ketene-(S,S)
      acetals and alcohols and synthesis of unsymmetrical biaryls.
AB  - A highly efficient BF3.OEt2-catalyzed formal dehydration C-C coupling reaction
      between readily available alpha-EWG ketene-(S,S)-acetals and various alcohols via
      direct substitution of the hydroxy group in alcohols has been developed. On the
      basis of this C-C coupling reaction, a series of alkylated alpha-EWG ketene-(S,S)
      acetals and functionalized 1,4-pentanedienes were prepared in high to excellent
      yields and the unsymmetrical biaryls were synthesized in good yields from the
      generated 1,4-pentanedienes and nitroalkanes through a one-pot annulation
      aromatization process.

PMID- 17194093
TI  - Copper-carbene complexes as catalysts in the synthesis of functionalized styrenes
      and aliphatic alkenes.
AB  - (NHC)-Cu (NHC = N-heterocyclic carbene) complexes efficiently catalyzed the
      methylenation of a variety of aliphatic and aromatic aldehydes and ketones in the
      presence of trimethylsilyldiazomethane, triphenylphosphine, and 2-propanol. The
      copper catalysts are not only inexpensive compared to rhodium complexes, but they
      also exhibit better functional group compatibility with aromatic aldehydes and
      ketones. Indeed very high yields were obtained for the formation of styrenes
      containing nitro, trifluoromethyl, amino, and ester groups, as well as for
      pyridine-, pyrrole-, and indole-substituted alkenes.

PMID- 17194094
TI  - Evaluation of the kinetic data for intramolecular 1,x-hydrogen shifts in alkyl
      radicals and structure/reactivity predictions from the carbocyclic model for the
      transition state.
AB  - Experimental and computational kinetic data for the intramolecular 1,x-hydrogen
      shift in alkyl radicals are compiled in Arrhenius format for x = 2-5. Significant
      experimental disparity remains, especially for x = 2 and 3. Experimental data for
      radicals with tert centers or bearing spectator substituents are lacking for all
      x, and none exist for x = 6. The common use of the strain energy of the
      unsubstituted (x+1)-carbocycle to coarsely model the activation energy for the
      1,x-shift is extended to explore more subtle differences in progressively methyl
      substituted systems by use of molecular mechanics estimates of differences in
      strain between radicals and carbocycles. For x = 5 and 6, a sterically driven
      increase in E is predicted for shifts in the tert --> tert class that apparently
      runs counter to the behavior of bimolecular hydrogen transfers. In contrast, a
      sterically driven decrease in E is predicted to result from spectator methyl
      groups for the prim --> prim reaction class for all x. There is no experimental
      basis to test these predictions; fragmentary computational evidence lends some
      support to the second but is ambiguous concerning the first. Possible
      deficiencies in the use of carbocycles as transition state models are discussed.

PMID- 17194095
TI  - Synthesis, stabilities, and redox behavior of mono-, di-, and tetracations
      composed of di(1-azulenyl)methylium units connected to a benzene ring by phenyl-
      and 2-thienylacetylene spacers. A concept of a cyanine-cyanine hybrid as a
      stabilized electrochromic system.
AB  - This paper describes the preparation of two tetracations 4a(4+) and 4b(4+)
      composed of di(1-azulenyl)methylium units based on a new structural principle of
      a cyanine-cyanine hybrid for the design of electrochromic materials with two
      color changes. Di- and monocations 5a(2+), 5b(2+) and 6a+, 6b+ composed of di(1
      azulenyl)methylium units were also prepared for the purpose of comparison. The
      pKR+ values of the tetracations are rather high despite their tetracationic
      structure, although the stability of these cations decreases with the increase of
      the number of the existing cation units. The cyclic voltammetry (CV) of these
      cations revealed the presumed multielectron redox properties. However, the
      tetracations did not exhibit the idealized electrochemical behavior, in which
      subsequent two-electron reduction was presumed as the cyanine-cyanine hybrid,
      probably due to the less effective electrochemical interaction among the positive
      charges. The scope of the creation of the novel polyelectrochromic materials
      taking the new structural principle is demonstrated by these examples.

PMID- 17194096
TI  - High-throughput five minute microwave accelerated glycosylation approach to the
      synthesis of nucleoside libraries.
AB  - The Vorbruggen glycosylation reaction was adapted into a one-step 5 min/130
      degrees C microwave assisted reaction. Triethanolamine in acetontrile containing
      2% water was determined to be optimal for the neutralization of trimethylsilyl
      triflate allowing for direct MPLC purification of the reaction mixture. When
      coupled with a NH3/methanol deprotection reaction, a high-throughput method of
      nucleoside library synthesis was enabled. The method was demonstrated by
      examining the ribosylation of 48 nitrogen containing heteroaromatic bases that
      included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine,
      two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4
      triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one
      alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in
      separable mixtures. Seven examples provided inseparable regioisomer mixtures of 
      two to three compounds (16 nucleosides), and three examples failed to yield
      isolable products. For the 45 single isomers isolated, the average two-step
      overall yield +/- SD was 26 +/- 16%, and the average purity +/- SD was 95 +/- 6%.
      A total of 58 different nucleosides were prepared of which 15 had not previously
      been accessed directly from glycosylation/deprotection of a readily available
      base.

PMID- 17194097
TI  - New chain-extended analogues of salacinol and blintol and their glycosidase
      inhibitory activities. Mapping the active-site requirements of human maltase
      glucoamylase.
AB  - The synthesis of new chain-extended sulfonium and selenonium salts of 1,4-anhydro
      4-thio-(or 4-seleno)-d-arabinitol, analogues of the naturally occurring
      glycosidase inhibitor salacinol, is described. Nucleophilic attack at the least
      hindered carbon atom of 4,6-O-benzylidene-2,5-di-O-p-methoxybenzyl-d-mannitol-1,3
      cyclic sulfate by 2,3,5-tri-O-p-methoxybenzyl-1,4-anhydro-4-thio-(or 4-seleno)-d
      arabinitol gave the sulfonium and selenonium sulfates, respectively. Subsequent
      deprotection with trifluoroacetic acid yielded the target compounds. In these
      analogues, an extended polyhydroxylated aliphatic side chain has been
      incorporated while maintaining the stereochemistry of C-2' and C-3' of salacinol
      or blintol. These compounds were designed to probe the premise that they would
      bind with higher affinity to glucosidases than salacinol because the extra
      hydroxyl groups in the acyclic chain would make favorable polar contacts within
      the active site. Both target compounds inhibited recombinant human maltase
      glucoamylase, one of the key intestinal enzymes involved in the breakdown of
      glucose oligosaccharides in the small intestine, with Ki values in the low
      micromolar range. Comparison of these values to those of related compounds
      synthesized in previous studies has provided a better understanding of structure
      activity relationships and the optimal stereochemistry at the different
      stereogenic centers required of an inhibitor of this enzyme. With respect to
      chain extension, the configurations at C-2' and C-4' are critical for activity,
      the configuration at C-3', bearing the sulfate moiety, being unimportant. The
      desired configuration at C-5' is also specified. However, comparison of the
      activities of the chain-extended analogues with those of salacinol and blintol
      indicates that there is no particular advantage of the chain-extension relative
      to salacinol or blintol. These results are similar to those reported earlier for
      kotalanol, a 7-carbon-extended derivative, versus salacinol against rat
      intestinal maltase, sucrase, and isomaltase.

PMID- 17194098
TI  - Thermal chemistry of bicyclo[4.2.0]oct-2-enes.
AB  - At 300 degrees C, bicyclo[4.2.0]oct-2-ene (1) isomerizes to bicyclo[2.2.2]oct-2
      ene (2) via a formal [1,3] sigmatropic carbon migration. Deuterium labels at C7
      and C8 were employed to probe for two-centered stereomutation resulting from C1
      C6 cleavage and for one-centered stereomutation resulting from C1-C8 cleavage,
      respectively. In addition, deuterium labeling allowed for the elucidation of the
      stereochemical preference of the [1,3] migration of 1 to 2. The two possible
      [1,3] carbon shift outcomes reflect a slight preference for migration with
      inversion rather than retention of stereochemistry; the si/sr product ratio is
      approximately 1.4. One-centered stereomutation is the dominant process in the
      thermal manifold of 1, with lesser amounts of fragmentation and [1,3] carbon
      migration processes being observed. All of these observations are consistent with
      a long-lived, conformationally promiscuous diradical intermediate.

PMID- 17194099
TI  - Synthesis of functionalized, unsymmetrical 1,3,4,6-tetrasubstituted 2,5
      diketopiperazines.
AB  - A general and efficient method for the synthesis of unsymmetrical 1,3,4,6
      tetrasubstituted 2,5-diketo- piperazines (DKPs) is described. Cyclization of N
      amide alkylated dipeptide methyl esters, followed by alkylation, furnished the
      corresponding tetrasubstituted DKPs in good overall yields. The influence of
      steric hindrance in the alkylation reactions appeared to be of lesser importance
      as long as reactive alkylating agents were used. Furthermore, we have
      demonstrated the use of tetrasubstituted DKPs as a scaffold for further chemical
      manipulations to produce novel DKPs with desired properties.

PMID- 17194100
TI  - Electrochemically promoted C-N bond formation from amines and CO2 in ionic liquid
      BMIm-BF4: Synthesis of carbamates.
AB  - A new electrochemical procedure for the synthesis of organic carbamates from
      amines and carbon dioxide has been developed using selective cathodic reduction
      of carbon dioxide in CO2-saturated room-temperature ionic liquid BMIm-BF4
      solutions containing amines 1a-j, followed by addition of EtI as an alkylating
      agent. The synthesis was carried out under mild (PCO2 = 1.0 atm, t = 55 degrees
      C) and safe conditions, and the use of volatile and toxic solvents and catalysts
      (according to the growing demand for ecofriendly synthetic methodologies), as
      well as of any supporting electrolyte (for a very easy workup of the reaction
      mixture), was avoided. Carbamates 2a-j were isolated in good to high yields.

PMID- 17194101
TI  - Enantioselective strecker reaction of phosphinoyl ketoimines catalyzed by in situ
      prepared chiral N,N'-dioxides.
AB  - The enantioselective Strecker reaction of N-diphenylphosphinoyl ketoimines has
      been achieved by use of in situ prepared chiral N,N'-dioxide catalyst from l
      piperidinamide 3f and m-chloroperoxybenzoic acid (m-CPBA). Excellent yields (up
      to 99%) and high enantioselectivities (up to 92% ee) were obtained. In
      particular, in situ prepared catalyst with readily available chiral material made
      the procedure more convenient. Moreover, the l-piperidinamide 3f-derived N,N'
      dioxide 9 could be recycled and reused at least five times without any loss of
      either catalytic activity or enantioselectivity.

PMID- 17194102
TI  - Studies toward the total synthesis of dumsin. 2. A second generation approach
      resulting in enantioselective construction of a functionalized ABC subunit of the
      tetranortriterpenoid insect antifeedant.
AB  - A synthesis of the ABC framework of dumsin is described. The optically active
      intermediate 9b, which is expeditiously assembled from 5-oxobornyl pivalate by
      the sequential implementation of an oxy-Cope rearrangement and an intramolecular
      ene reaction, proved to be suitably functionalized for ultimate conversion to 5.
      The synthesis plan relies on two approaches to this targeted intermediate. In the
      first, the exocyclic double bond introduced during EtAlCl2-promoted closure of
      aldehyde 10b is cleaved to leave a carbonyl group that is amenable to hydride
      reduction and elimination of water. Cleavage of the resulting double bond with
      ruthenium tetroxide provided the seco ketoacid. The same advanced intermediate
      was obtained by initially positioning the double bond internal to the five
      membered ring in advance of transient ring expansion via diketone formation and
      intramolecular aldolization. Both of these approaches bypass the complications
      arising from the substantial steric congestion prevailing in these structural
      networks. The task of covalently positioning an oxygen atom adjacent to the gem
      dimethyl-substituted carbon in 5 was properly realized by oxidative
      decarboxylation. The stereochemical assignments to many of the intermediates were
      confirmed by an X-ray crystallographic analysis of 43.

PMID- 17194103
TI  - Highly efficient route to fused polycyclic aromatics via palladium-catalyzed
      aryne annulation by aryl halides.
AB  - Polycyclic aromatic and heteroaromatic hydrocarbons have been synthesized in high
      yield by two different processes involving the Pd-catalyzed annulation of arynes.
      The first process involves a Pd-catalyzed annulation of arynes by 2-halobiaryls
      and related vinylic halides. The second process utilizes a Pd-catalyzed double
      annulation of arynes by simple aryl halides. Both processes appear to involve the
      catalytic, stepwise coupling of two very reactive substrates, an aryne and an
      organopalladium species, to generate excellent yields of cross-coupled products.

PMID- 17194104
TI  - Electronic effects of peripheral substituents at porphyrin meso positions.
AB  - Porphyrins are stable molecules with a macrocyclic conjugated system and often
      peripheral substituents. This unique structure makes the electronic properties of
      the four meso-carbons (the methine bridges) nearly identical. Replacement of the
      weakly electron-polarizing 2,4-vinyl groups of protoporphyrin IX with strongly
      electron-polarizing acetyl groups not only leads to much lower meso-carbon
      reactivities toward electrophilic aromatic substitution but also results in a
      significant meso-selectivity (the beta- and gamma-meso-positions become much more
      nucleophilic (basic) than the alpha- and delta-meso-positions). To further
      investigate the relationship between the porphyrin meso-carbon reactivities and
      the peripheral substituents, two monoacetylporphyrin analogues also were
      synthesized. This investigation not only leads to empirical rules for predicting
      porphyrin meso-carbon selectivities but also provides important models for
      theoretical calculations of porphyrin aromaticity.

PMID- 17194105
TI  - Bisoxazoline-Lewis acid-catalyzed direct-electron demand oxo-hetero-Diels-Alder
      reactions of N-oxy-pyridine aldehyde and ketone derivatives.
AB  - A general catalytic oxo-hetero-Diels-Alder reaction for pro-chiral aldehyde and
      ketone N-oxy-pyridines is presented. The catalytic and asymmetric oxo-hetero
      Diels-Alder reaction of electron-rich dienes with N-oxy-pyridine-2-carbaldehyde
      and ketone derivatives, catalyzed by chiral copper(II)-bisoxazoline complexes,
      gives optically active six-membered oxygen heterocycles in moderate to good
      yields and with excellent enantioselectivities.

PMID- 17194106
TI  - Enantioselective fluorination of tert-butoxycarbonyl lactones and lactams
      catalyzed by chiral Pd(II)-bisphosphine complexes.
AB  - An efficient catalytic enantioselective fluorination of tert-butoxycarbonyl
      lactones and lactams is reported. Reactions of the lactone substrates proceeded
      smoothly in an alcoholic solvent with a catalytic amount of chiral Pd(II)
      complex. In the case of the less acidic lactam substrates, concurrent use of the
      Pd complex and 2,6-lutidine as a cocatalyst was effective. Under the reaction
      conditions, the fluorinated lactones and lactams were obtained in good yield with
      excellent enantioselectivity (94-99% ee).

PMID- 17194108
TI  - Foiled carbenes revisited: When sigma-stabilization surpasses pi-stabilization.
AB  - The bicyclic alkenylidenes 9 (bicyclo[3.2.1]oct-2-en-8-ylidene) and 17
      (bicyclo[3.3.1]non-2-en-9-ylidene) were claimed to be stabilized foiled carbenes.
      Our B3LYP and MP2 computations confirm previous experimental data. Moreover, they
      show that these carbenes are very reactive and rearrange rapidly, mainly through
      a 1,2-vinyl shift by overcoming a low barrier (1.2 to 5.4 kcal/mol). This is in
      contrast to the high barriers (up to 30 kcal/mol) predicted for the same type of
      rearrangements in norborn-2-en-7-ylidene derivatives. In 17 and bicyclo[4.1.1]oct
      2-en-7-ylidene (23), the divalent carbon atom is even bent away from the double
      bond!

PMID- 17194107
TI  - Synthesis of indenes by the transition metal-mediated carboannulation of alkynes.
AB  - The synthesis of highly substituted indenes has been achieved by three different
      transition metal-mediated methods. The first method involves the palladium
      catalyzed carboannulation of internal alkynes. The second method utilizes a two
      step approach, which involves first the palladium/copper-catalyzed cross-coupling
      of terminal alkynes with appropriately functionalized aryl halides, followed by
      copper-catalyzed intramolecular cyclization. The third method involves
      intermolecular palladium-catalyzed arylation of the arylalkynes formed in the
      first step of the second method.

PMID- 17194109
TI  - Convenient method to access new 4,4-dialkoxy- and 4,4-diaryloxy-diaza-s-indacene
      dyes: Synthesis and spectroscopic evaluation.
AB  - A straightforward method for the synthesis of original 4,4-dialkoxy- or 4,4
      diaryloxy-diaza-s-indacenes (BODIPY) derivatives obtained by treatment of BODIPY
      1 with various alcohols in the presence of AlCl3 is described. The novel
      compounds are characterized by spectroscopic properties similar to those of the
      parent BODIPY 1, absorption and emission spectra with similar band shapes, high
      molar absorption coefficients (epsilon lambda max approximately 80,000 M(-1) cm(
      1)), and for most of them high fluorescence quantum yields (Phi exp from 0.52 to
      0.71). Among all of the new compounds synthesized, the dye 2 h exhibits higher
      fluorescence quantum yield (0.71) and lifetime (4.09 ns) than compound 1 and a
      good chemical stability toward conditions compatible with biological cell-based
      assays.

PMID- 17194110
TI  - N-carbonylation of lithium azaenolates of amides, formamides, ureas, and
      carbamates with carbon monoxide mediated by selenium.
AB  - N-Carbonylation of less nucleophilic nitrogen compounds was achieved by the
      reaction of the lithium azaenolates with carbon monoxide and selenium. This
      reaction proceeds in the cases of amides, formamides, ureas, and carbamates,
      leading to the formation of the corresponding carbamoselenoates in good to high
      yields after trapping with BuI.

PMID- 17194111
TI  - Fliplike motion in the thalidomide dimer: Conformational analysis of (R)
      thalidomide using vibrational circular dichroism spectroscopy.
AB  - The dynamic fliplike motion in the (R)-thalidomide dimer has been reported for
      the first time. The vibrational circular dichroism (VCD) spectrum of (R)
      thalidomide in DMSO-d6 indicates the characteristic nu(CO) bands with opposite
      signs and reflects the structural property of the equatorial configuration of the
      phthalimide ring. On the other hand, the VCD spectrum of (R)-thalidomide in CDCl3
      exhibits a different pattern of nu(CO) bands and suggests the fliplike motion in
      dimer forms. This novel insight for the dimer forms would be helpful for the
      understanding of the structure-activity relationship for thalidomide.

PMID- 17194112
TI  - Reversible 2D pseudopolyrotaxanes based on cyclodextrins and cucurbit[6]uril.
AB  - In this paper, a pseudorotaxane (2) was synthesized by reaction of cucurbit
      [6]uril with 6-[(6-aminohexyl)amino]-6-deoxy-beta-cyclodextrin chloride.
      Subsequently, pseudorotaxanes 2 were further assembled to form a 2D
      pseudopolyrotaxane (3) through an alpha,omega-PPG2000 diamino polymer threading
      the cavities of cyclodextrins in 2, and the resulting pseudopolyrotaxane was
      comprehensively characterized by FT-IR, NMR, TG-DTA, elemental analysis, and
      transmission electron microscopy. Significantly, the 2D pseudopolyrotaxane can
      turn into a main-chain pseudopolyrotaxane in the presence of base, and then the
      addition of alpha-cyclodextrins may result in a reversible switch between two
      different 2D pseudopolyrotaxanes.

PMID- 17194113
TI  - Microwave-mediated heterocyclization to benzimidazo[2,1-b]quinazolin-12(5H)-ones.
AB  - An effective route to benzimidazo[2,1-b]quinazolin-12(5H)-ones from commercially
      available o-aryl isothiocyanate esters and o-phenylenediamines is reported. This
      method accommodates a variety of substituents on either starting material and
      proceeds under microwave irradiation in the presence of barium hydroxide,
      conditions that do not hydrolyze methyl ester substituents. The pharmacologically
      pertinent benzimidazoquinazolinone heterocycle is delivered in excellent yield
      and purity via both solution- and solid-phase protocols, the latter involving
      traceless release from the resin.

PMID- 17194114
TI  - 4-Substituted-alpha,alpha-diaryl-prolinols improve the enantioselective catalytic
      epoxidation of alpha,beta-enones.
AB  - To seek novel metal-free organic catalysts for epoxidation with high
      stereoselectivity, a series of 4-substituted-alpha,alpha-diaryl-prolinols were
      synthesized in four steps from trans-4-hydroxyl-L-proline. These prolinol
      derivatives catalyzed the asymmetric epoxidation of alpha,beta-enones to give the
      corresponding chiral epoxides in good yields and high enantioselectivities under
      mild reaction conditions. Studies of substituent effects on enantioselectivity
      revealed that steric bulk and electronic effect promoted higher
      enantioselectivity, and prolinol 8a was found to be the best catalyst until now.

PMID- 17194116
TI  - How well can new-generation density functionals describe protonated epoxides
      where older functionals fail?
AB  - In a recent article, Carlier et al. (J. Org. Chem. 2006, 71, 1592) examined the
      prediction of several DFT functionals and showed that the most popular density
      functional, B3LYP, and 15 others fail badly for the prediction of the structure
      of protonated 2-methyl-1,2-epoxypropane. In this note, we compare the performance
      of several recently developed density functionals for the calculation of
      structures and energetics of protonated cyclic ethers, including epoxides. We
      found that several of the newly developed DFT methods perform better than B3LYP
      or any of the other 17 functionals examined by Carlier. We conclude that a
      recently published functional, M05-2X, has greatly improved performance for an
      unsymmetrical protonated epoxide, and we recommend this functional for studies
      that involve protonated epoxides and protonated ethers.

PMID- 17194115
TI  - Practical stereoselective synthesis of an alpha-trifluoromethyl-alpha-alkyl
      epoxide via a diastereoselective trifluoromethylation reaction.
AB  - A practical stereoselective synthesis is reported for an alpha-trifluoromethyl
      alpha-alkyl epoxide (1), which is an important pharmaceutical intermediate. The
      key step involves a chiral auxiliary-controlled asymmetric trifluoromethylation
      reaction for the introduction of the unique trifluoromethyl-substituted tertiary
      alcohol stereogenic center in the target molecule. The fluoride-initiated CF3
      addition to chiral keto ester 6a proceeded with a diastereoselectivity up to
      86:14. The major diastereomer was readily obtained with a >99.5:0.5 dr through a
      simple crystallization of the crude product mixture.

PMID- 17194118
TI  - Number 83.
AB  - Reviews are listed in order of appearance in the sources indicated. In
      multidisciplinary review journals, only those reviews which fall within the scope
      of this Journal are included. Sources are listed alphabetically in three
      categories: regularly issued review journals and series volumes, contributed
      volumes, and other monographs. Titles are numbered serially, and these numbers
      are used for reference in the index. Major English-language sources of critical
      reviews are covered. Encyclopedic treatises, annual surveys such as Specialist
      Periodical Reports, and compilations of symposia proceedings are omitted. This
      installment of Recent Reviews covers principally the middle part of the 2006
      literature. Previous installment: J. Org. Chem. 2006, 71(20), 7923-30.

PMID- 17194117
TI  - Removal of acid-labile protecting groups on carbohydrates using water-tolerant
      and recoverable vanadyl triflate catalyst.
AB  - Acetal, trityl, and TBDMS protecting groups on saccharides were subjected to
      alcoholysis using a catalytic amount of vanadyl triflate in an MeOH-CH2Cl2
      solvent system. The configuration at the anomeric positions of saccharides was
      retained, and no glycosidic bond cleavage and oxidation of sulfides were
      observed. The presented method was easily implemented, compatible with diverse
      functional groups, and regioselective in some cases.

PMID- 17194119
TI  - Multiplexed proteomic reactor for the processing of proteomic samples.
AB  - We report the development of a 96-well plate proteomic reactor for gel-free
      processing of minute amounts of complex proteomic samples. The device performs
      multiplexed trapping, enrichment, and biochemical processing of proteins,
      resulting in concentrated peptide solutions ready for mass spectrometric
      analysis. Individual wells on the reactor can process up to 2 microg of protein.
      We also report the coupling of the plate proteomic reactor with protein
      fractionation using size-exclusion chromatography for large-scale identification
      of proteins. To illustrate the potential of this approach, we separated 400
      microg of MCF7 cell lysate using size-exclusion chromatography and processed 35
      protein fractions on the reactor plate. Using stringent criteria when searching
      the data, a total of 875 unique proteins were identified. More relaxed searching
      conditions associated with a 1% false positive rate led to the identification of
      2683 unique proteins, meaning that one protein was identified per 3-10 ng of
      total protein lysate loaded on the reactor plate.

PMID- 17194120
TI  - Multianalyte chemical identification and quantitation using a single radio
      frequency identification sensor.
AB  - We demonstrate an approach for multianalyte chemical identification and
      quantitation using a single conventional radio frequency identification (RFID)
      tag that has been adapted for chemical sensing. Unlike other approaches of using
      RFID sensors, where a special tag should be designed at a much higher cost, we
      utilize a conventional RFID tag and coat it with a chemically sensitive film. As
      an example, we demonstrate detection of several vapors of industrial, health, law
      enforcement, and security interest (ethanol, methanol, acetonitrile, water
      vapors) with a single 13.56-MHz RFID tag coated with a solid polymer electrolyte
      sensing film. By measuring simultaneously several parameters of the complex
      impedance from such an RFID sensor and applying multivariate statistical analysis
      methods, we were able to identify and quantify several vapors of interest. With a
      careful selection of the sensing film and measurement conditions, we achieved
      parts-per-billion vapor detection limits in air. These RFID sensors are very
      attractive as ubiquitous multianalyte distributed sensor networks.

PMID- 17194121
TI  - Peptide-nucleic acid-modified ion-sensitive field-effect transistor-based
      biosensor for direct detection of DNA hybridization.
AB  - Here, we report the development of a peptide-nucleic acid (PNA)-modified ion
      sensitive field-effect transistor (IS-FET)-based biosensor that takes advantage
      of the change in the surface potential upon hybridization of a negatively charged
      DNA. PNA was immobilized on a silicon nitride gate insulator by an addition
      reaction between a maleimide group introduced on the gate surface, the
      succinimide group of N-(6-maleimidocaproyloxy) succinimide, and the thiol group
      of the terminal cysteine in PNA. The surface was characterized after each step of
      the reaction by X-ray photoelectron spectroscopy analysis, and the kinetic
      analysis of the hybridization events was assessed by surface plasmon resonance.
      In addition, we measured the -potential before and after PNA-DNA hybridization in
      the presence of counterions to investigate the change in surface charge density
      at the surface-solution interface within the order of the Debye length. On the
      basis of the zeta-potential, the surface charge density, DeltaQ, calculated using
      the Grahame equation was approximately 4.0 x 10(-3) C/m2 and the estimated number
      of hybridized molecules was at least 1.7 x 10(11)/cm2. The I-V characteristics
      revealed that the PNA-DNA duplexes induce a positive shift in the threshold
      voltage, VT, and a decrease in the saturated drain current, ID. These results
      demonstrate that direct detection of DNA hybridization should be possible using a
      PNA-modified IS-FET-based biosensor. PNA is particularly advantageous for this
      system because it enables highly specific and selective binding at low ionic
      strength.

PMID- 17194122
TI  - Time-resolved pH/pO2 mapping with luminescent hybrid sensors.
AB  - A method for simultaneous and referenced 2D mapping of pH and pO2 is described.
      The experimental setup combines a fast gateable CCD camera as detector, a LED as
      excitation light source and a single-layer sensor membrane as optical transducer.
      The planar optode comprises a lipophilic fluorescein derivative (lifetime
      approximately 5 ns) and platinum(II) mesotetrakis(pentafluorophenyl)porphyrin
      (approximately 70 micros in the absence of a quencher) immobilized in a hydrogel
      matrix. Depending on the fluorescent pH indicator, a pH transition in the
      physiological range (pH 6-pH 8) or in the near-basic region (pH 7-pH 9) can be
      achieved. The measuring scheme involves the time-resolved acquisition of images
      in three windows during a series of square-shaped excitation pulses. A method
      allowing the calculation of both parameters from these three images is presented.
      The pH/pO2 hybrid sensor incorporating the pH indicator 2',7'-dihexyl-5(6)-N
      octadecyl-carboxamidofluorescein was characterized in detail. The pH and pO2 were
      determined with a maximum deviation of 0.03 pH unit and 6.5 hPa pO2,
      respectively, within the range of pH 7.6-pH 8.7 and 0-200 hPa pO2 in test
      measurements. The ionic strength (IS) cross-sensitivity was found to be
      relatively small (pH/IS < 3.5 x 10(-4) mM(-1) and pO2/IS <-0.053 hPa mM(-1) at a
      transition from 0.5 to 0.1 M IS). Whereas a strong temperature effect on the
      sensor signal was observed (DeltapH/DeltaT = 0.011-0.034 K-1 and DeltapO2/DeltaT
      = 1.85-7.17 hPa K-1 in the range from 277 to 308 K). Examples of pH/pO2 images
      obtained in natural marine sediment are presented.

PMID- 17194123
TI  - Solvent-free MALDI-MS for the analysis of a membrane protein via the mini ball
      mill approach: case study of bacteriorhodopsin.
AB  - A mini ball mill (MBM) solvent-free matrix-assisted laser desorption/ionization
      (MALDI) mass spectrometry (MS) method allows for the analysis of
      bacteriorhodopsin (BR), an integral membrane protein that previously presented
      special analytical problems. For well-defined signals in the molecular ion region
      of the analytes, a desalting procedure of the MBM sample directly on the MALDI
      target plate was used to reduce adduction by sodium and other cations that are
      normally attendant with hydrophobic peptides and proteins as a result of the
      sample preparation procedure. Mass analysis of the intact hydrophobic protein and
      the few hydrophobic and hydrophilic tryptic peptides available in the digest is
      demonstrated with this robust new approach. MS and MS/MS spectra of BR tryptic
      peptides and intact protein were generally superior to the traditional solvent
      based method using the desalted "dry" MALDI preparation procedure. The solvent
      free method expands the range of peptides that can be effectively analyzed by
      MALDI-MS to those that are hydrophobic and solubility-limited.

PMID- 17194124
TI  - Hydration and energy dissipation measurements of biomolecules on a piezoelectric
      quartz oscillator by admittance analyses.
AB  - By using a 27-MHz piezoelectric quartz oscillator connected with a vector network
      analyzer, we obtained resonance frequency decreases (-DeltaFwater) and energy
      dissipation increases (DeltaDwater) during binding of biotinylated bovine serum
      albumin, biotinylated ssDNA, biotinylated dsDNA, and biotinylated pullulan to a
      NeutrAvidin-immobilized 27-MHz quartz crystal microbalance (QCM) plate in aqueous
      solution, as well as in the wet air phase (98% humidity, -DeltaFwet and
      DeltaDwet) and in the dry air phase (-DeltaFair and DeltaDair). -DeltaFwater
      indicates the total mass of the molecule, bound water, and vibrated water in
      aqueous solutions. -DeltaFwet indicates the total mass of the molecule and bound
      water. -DeltaFair simply shows the real mass of the molecule on the QCM. In terms
      of results, (-DeltaFwet)/(-DeltaFair) values indicated the bound water ratios per
      unit biomolecular mass were on the order of pullulan (2.1-2.2) > DNAs = proteins
      (1.4-1.6) > polystyrene (1.0). The (-DeltaFwater)/(-DeltaFair) values indicated
      the hydrodynamic water (bound and vibrated water) ratios per unit biomolecular
      mass were on the order of dsDNA (6.5) > ssDNA = pullulan (3.5-4.4) > proteins
      (2.4-2.5) > polystyrene (1.0). Energy dissipation parameters per unit mass in
      water (DeltaDwater/(-DeltaFair)) were on the order of pullulan > dsDNA > ssDNA >
      proteins > polystyrene. Energy dissipation in the wet and dry air phases
      (DeltaDwet and DeltaDair) were negligibly small, which indicates even these
      biomolecules act as elastic membranes in the air phase (without aqueous
      solution). We obtained a good linear relationship between [(-DeltaFwater)/(
      DeltaFair) - 1], which is indicative of hydration and DeltaDwater/(-DeltaFair) of
      proteins. The aforementioned values suggest that the energy dissipation of
      proteins was mainly caused by hydration and that proteins themselves are elastic
      molecules without energy dissipation in aqueous solutions. On the contrary, plots
      in cases of denatured proteins, DNAs, and pullulans were relatively deviant
      toward the large hydration and energy dissipation from the theoretical line as
      perfect elastic materials, meaning that the large energy dissipation occurs
      because of viscoelastic properties of denatured proteins, linear DNAs, and
      pullulans in the water phase, in addition to energy dissipation due to the
      hydration of molecules. These two parameters could characterize various
      biomolecules with structural properties in aqueous solutions.

PMID- 17194125
TI  - Monitoring diet effects via biofluids and their implications for metabolomics
      studies.
AB  - The effect of diet on metabolites found in rat urine samples has been
      investigated using nuclear magnetic resonance (NMR) and a new ambient ionization
      mass spectrometry experiment, extractive electrospray ionization mass
      spectrometry (EESI-MS). Urine samples from rats with three different dietary
      regimens were readily distinguished using multivariate statistical analysis on
      metabolites detected by NMR and MS. To observe the effect of diet on metabolic
      pathways, metabolites related to specific pathways were also investigated using
      multivariate statistical analysis. Discrimination is increased by making
      observations on restricted compound sets. Changes in diet at 24-h intervals led
      to predictable changes in the spectral data. Principal component analysis was
      used to separate the rats into groups according to their different dietary
      regimens using the full NMR, EESI-MS data or restricted sets of peaks in the mass
      spectra corresponding only to metabolites found in the urea cycle and metabolism
      of amino groups pathway. By contrast, multivariate analysis of variance from the
      score plots showed that metabolites of purine metabolism obscure the
      classification relative to the full metabolite set. These results suggest that it
      may be possible to reduce the number of statistical variables used by monitoring
      the biochemical variability of particular pathways. It should also be possible by
      this procedure to reduce the effect of diet in the biofluid samples for such
      purposes as disease detection.

PMID- 17194126
TI  - Structure and electrochemical properties of carbon films prepared by a electron
      cyclotron resonance sputtering method.
AB  - This paper describes the characterization, electrochemical properties, and
      applications of carbon films prepared by the electron cyclotron resonance (ECR)
      sputtering method. The ECR-sputtered carbon film was deposited within several
      minutes at room temperature. The optimized sputtering conditions significantly
      change the film structure, which includes many more sp3 bonds (sp3/sp2 = 0.702)
      than previously reported film (sp3/sp2 = 0.274)1 with an extremely flat surface
      (0.7 A). The ECR-sputtered carbon films exhibit excellent electrochemical
      properties. For example, they have nearly the same potential window in the
      positive direction as that of high-quality, boron-doped diamond (moderately
      doped, 10(19)-10(20) boron atoms/cm3)2 and an even wider potential window in the
      negative direction with a low background current, high stability, and suppression
      of fouling by electroactive species without pretreatment. The electron-transfer
      rates at ECR-sputtered carbon films are similar to those of glassy carbon (GC)
      for Ru(NH3)(6)(2+)/(3+) and Fe(CN)(6)(3-)/(4-), whereas they are much slower than
      those of GC for Fe2+/3+, dopamine oxidation, and O2 reduction due to weak
      interactions between electroactive species and the ECR-sputtered carbon film
      surface. Such a response can be attributed to the ultraflat surface and low
      surface O/C ratios of ECR-sputtered carbon films. ECR-sputtered carbon film is
      advantageous for measuring biochemicals with high oxidation potentials because of
      its wide potential window and high stability. Highly reproducible and well
      defined cyclic voltammograms were obtained for histamine and azide ions with a
      peak potential at 1.25 and 1.12 V vs Ag/AgCl, respectively. The film is very
      stable for continuous voltammetry measurements in 10 microM bisphenol A, which
      usually fouls the electrode surface with oxidation products.

PMID- 17194127
TI  - Separation of C2-naphthalenes by gas chromatography x fourier transform infrared
      spectroscopy (GC x FT-IR): two-dimensional separation approach.
AB  - A two-dimensional separation approach involving gas chromatography (GC) and
      Fourier transform infrared spectroscopy (FT-IR) is used to separate C2
      naphthalene isomers at or near baseline resolution. In addition to GC separation,
      the FT-IR also plays an important role in the separation, as well as its
      traditional role of detection and identification. This two-dimensional separation
      approach for the analysis of a C2-naphthalene isomeric mixture is a good example
      of separation design based on molecular difference and the characteristics of an
      analytical instrument. The details of this two-dimensional separation are
      discussed, along with the advantages and limitations of this approach. While two
      (or multiple-)dimensional separations have demonstrated superior capabilities in
      the characterization of complex, largely unknown mixtures, the development of
      GCxFT-IR illustrates the applicability of this analytical approach in the
      separation of simpler but still challenging, mixtures. The GCxFT-IR results have
      extended this approach toward its application to the analysis of samples of more
      complicated composition.

PMID- 17194128
TI  - Pore-scale dispersion in electrokinetic flow through a random sphere packing.
AB  - The three-dimensional velocity field and corresponding hydrodynamic dispersion in
      electrokinetic flow through a random bulk packing of impermeable, nonconducting
      spheres are studied by quantitative numerical analysis. First, a fixed bed with
      interparticle porosity of 0.38 is generated using a parallel collective
      rearrangement algorithm. Then, the interparticle velocity field is calculated
      using the lattice-Boltzmann (LB) method, and a random-walk particle-tracking
      method is finally employed to model advection-diffusion of an inert tracer in the
      LB velocity field. We demonstrate that the pore-scale velocity profile for
      electroosmotic flow (EOF) is nonuniform even under most ideal conditions,
      including a negligible thickness of the electrical double layer compared to the
      mean pore size, a uniform distribution of the electrokinetic potential at the
      solid-liquid interface, and the absence of applied pressure gradients. This EOF
      dynamics is caused by a nonuniform distribution of the local electrical field
      strength in the sphere packing and engenders significant hydrodynamic dispersion
      compared to pluglike EOF through a single straight channel. Both transient and
      asymptotic dispersion behaviors are analyzed for EOF in the context of packing
      microstructure and are compared to pressure-driven flow in dependence of the
      average velocity through the bed. A better hydrodynamic performance of EOF
      originates in a still much smaller amplitude of velocity fluctuations on a
      mesoscopic scale (covering several particle diameters), as well as on the
      microscopic scale of an individual pore.

PMID- 17194130
TI  - Two- and three-dimensional imaging of multicomponent systems using scanning
      thermal microscopy and localized thermomechanical analysis.
AB  - The aim of this study was to develop a novel approach to the spatial
      characterization of multicomponent samples, based on the emergent technique of
      microthermal analysis. More specifically, we present an assessment of the use of
      scanning thermal microscopy as a means of component mapping via thermal
      conductivity; we include a new statistical approach to data handling, which
      allows reduction of topographic effects. We also introduce a novel three
      dimensional mapping technique based on localized thermomechanical analysis.
      Tablets of paracetamol and hyproxypropyl methylcellulose (HPMC) and 50:50 mixes
      of the two were prepared and the materials characterized in scanning and
      localized modes using a TA Instruments 2990 microthermal analyzer with a
      Thermomicroscopes Explorer AFM head and Wollaston wire thermal probe. L-TMA
      studies of the pure components indicated markedly differing thermal responses,
      with the paracetamol showing a sharp melting accompanied by a probe pull-in
      effect, while HPMC showed only thermal expansion over the temperature range
      studied. Thermal conductivity and topographic images indicated that two
      dimensional differentiation between the components was possible in scanning mode.
      A means of delineating the relative contribution of the topographic and
      conductivity effects was developed based on a regression analysis of the thermal
      conductivity measurements on a set of terms representing the local surface
      curvature. The results of three-dimensional imaging using a grid of L-TMA
      measurements is presented. This technique utilized the distinct thermal responses
      of the two components to allow the probe to melt through the paracetamol down to
      the underlying HPMC. The advantages and limitations of this novel imaging method
      are discussed in the context of pharmaceutical and broader uses of the approach.

PMID- 17194129
TI  - Microfluidic flow-flash: method for investigating protein dynamics.
AB  - We report a new method, microfluidic flow-flash, for measuring protein reaction
      kinetics. The method couples a microscope imaging detection system with a
      microfluidic flow cell to reduce data acquisition times and sample consumption.
      This combination allows for the simultaneous collection of spectral and temporal
      information. The microfluidic flow cell design utilizes three-dimensional sheath
      flow to reduce sample dispersion and minimize sample consumption. The ability to
      alter the flow rates in the microfluidic flow cells allows a variety of time
      scales to be studied with submillisecond time resolution. The imaging detection
      system can be coupled with several spectroscopic probes including fluorescence
      and UV/visible absorbance spectroscopy. Here, we utilize the microfluidic flow
      flash method to probe the kinetics of CO recombination or O2 binding to myoglobin
      after the laser-induced photolysis of CO from myoglobin by UV/visible absorbance
      spectral imaging.

PMID- 17194131
TI  - Combination of immunosensor detection with viability testing and confirmation
      using the polymerase chain reaction and culture.
AB  - Rapid and accurate differential determination of viable versus nonviable microbes
      is critical for formulation of an appropriate response after pathogen detection.
      Sensors for rapid bacterial identification can be used for applications ranging
      from environmental monitoring and homeland defense to food process monitoring,
      but few provide viability information. This study combines the rapid screening
      capability of the array biosensor using an immunoassay format with methods for
      determination of viability. Additionally, cells captured by the immobilized
      antibodies can be cultured following fluorescence imaging to further confirm
      viability and for cell population expansion for further characterization, e.g.,
      strain identification or antibiotic susceptibility testing. Finally, we
      demonstrate analysis of captured bacteria using the polymerase chain reaction
      (PCR). PCR results for waveguide-captured cells were 3 orders of magnitude more
      sensitive than the fluorescence immunoassay and can also provide additional
      genetic information on the captured microbes. These approaches can be used to
      rapidly detect and distinguish viable versus nonviable and pathogenic versus
      nonpathogenic captured organisms, provide culture materials for further analysis
      on a shorter time scale, and assess the efficacy of decontamination or
      sterilization procedures.

PMID- 17194132
TI  - High-speed camera imaging for laser ablation process: for further reliable
      elemental analysis using inductively coupled plasma-mass spectrometry.
AB  - Production of laser ablation-induced sample aerosols has been visualized using a
      high-speed camera device coupled with shadowgraphy technique. The time resolution
      of the method is 1 micros, and production of the sample grains was successfully
      defined by the imaging system. An argon-fluoride excimer laser operated at 193-nm
      wavelength was used to ablate the solid samples. When the laser was shot onto the
      sample (Si wafer), a dome-shaped dark area appeared at the ablation pit. This
      dark area reflects changes in refractive index of ambient He probably due to
      emission of electrons or ions from the ablation pit. The dark area expanded
      hemispherically from the ablation pit with a velocity close to the speed of sound
      (approximately 1000 m/s for He at 300 K). This was followed by the excitation or
      ionization of the vaporized sample, known as the plasma plume. Immediately after
      the formation of the plasma plume, sample aerosols were produced and released
      from the ablation pit along the propagation of the laser-induced shockwave.
      Production of the sample aerosols was significantly delayed (approximately 4
      micros) from the onset of the laser shot. The typical speed of particles released
      from the ablation pit was 100-200 m/s, which was significantly slower than the
      reported velocity of the plasma plume expansion (104 m/s). Since the initial
      measured speed of the sample particles was rather close to the speed of sound,
      the sample aerosols could be rapidly decelerated to the terminal velocity by a
      gas drag force with ambient He. The release angle of the sample aerosols from the
      ablation pit was very shallow (<10 degrees ), which may be due to the downforce
      produced by the thermal expansion of the ambient gas above the ablation pit. The
      shallower release angle and the contribution of the downforce probably results in
      the redeposition of sample aerosols or vapor around the ablation pit. In fact,
      the degree of sample redeposition around the ablation pit can be effectively
      minimized by evacuation the sample cell down to 20 kPa. In the case of glass
      samples, almost no visible laser-induced sample particles could be found using
      the spatial resolution of our device. This was mainly due to the smaller size
      distribution of the sample aerosols from the glass materials. Differences in size
      distribution of the sample aerosols between Si wafers and glass materials can
      affect analytical sensitivity and precision of elemental analyses using the laser
      ablation-ICP-mass spectrometry (LA-ICPMS). Although details of the mechanism of
      production and release of the sample aerosols from the ablation pit are not fully
      understood, the present imaging device for laser ablation has various
      implications for further precise elemental and isotopic analyses using LA-ICPMS.

PMID- 17194133
TI  - Hydrogen/deuterium scrambling during quadrupole time-of-flight MS/MS analysis of
      a zinc-binding protein domain.
AB  - It remains an open question as to whether experiments involving collision-induced
      dissociation (CID) can provide a viable approach for monitoring spatially
      resolved deuteration levels in electrosprayed polypeptide ions. A number of
      laboratories reported the successful application of CID following solution-phase
      H/D exchange (HDX), whereas others found that H/D scrambling precluded site
      specific measurements. The aim of the current work is to help clarify the general
      feasibility of HDX-CID methods, using a 22-residue zinc-bound protein domain (Zn
      ZBD) as model system. Metal binding in Zn-ZBD should confer structural rigidity,
      and the presence of several basic residues should sequester mobile charge
      carriers in the gas phase. Both of these factors were expected to suppress the
      extent of scrambling. HDX was carried out by employing rapid on-line mixing,
      thereby mimicking conditions typically encountered in kinetic pulse-labeling
      studies. Quadrupole time-of-flight MS/MS of pulse-labeled Zn-ZBD provides high
      sequence coverage. However, the measured fragment deuteration levels do not
      correlate with the known H-bonding pattern of Zn-ZBD, suggesting the occurrence
      of extensive scrambling. Instead of showing a uniform distribution, the fragment
      ions reveal a distinct nonrandom pattern of deuteration levels. In the absence of
      prior information, these data could erroneously be ascribed to the presence of
      protected sites. However, the observed patterns clearly originate from other
      factors; possibly they are caused by modulations of the amide CID efficiency by
      kinetic isotope effects. It is concluded that scrambling does not represent the
      only conceptual problem in HDX-CID studies and that control experiments on
      uniformly labeled samples are essential for ruling out interpretation artifacts.

PMID- 17194135
TI  - Metabolic profiling of liver from hypercholesterolemic pigs fed rye or wheat
      fiber and from normal pigs. High-resolution magic angle spinning 1H NMR
      spectroscopic study.
AB  - This study presents the first application of a high-resolution magic angle
      spinning 1H NMR approach to elucidate the metabolic effects of a
      hypercholesterolemic condition and two high-fiber diets based on rye and wheat
      bread, respectively, in intact pig liver biopsy samples. Standard 1D and spin
      echo 1H spectra were acquired on a total of 20 biopsy samples, and 2D total
      correlation spectroscopy experiments were carried out on selected samples for
      assignment of the observed resonances. Principal component analyses and partial
      least-squares regression discriminant analysis revealed differences in the
      hepatic lipid content and choline-containing compounds between normal and
      hypercholesterolemic pigs. In addition, the results demonstrated that the liver
      metabolite profile of hypercholesterolemic pigs fed a high-fiber rye bread
      differed from that of pigs fed high-fiber wheat bread with respect to both the
      lipoprotein fractions and the choline-containing compounds. These findings
      suggest that earlier reports on high-fiber rye diet-induced effects on plasma
      HDL/LDL content partially can be ascribed to effects on liver cholesterol
      metabolism and that the hepatic phospholipase pathways of phosphatidylcholine
      breakdown are affected by the high-fiber rye diet.

PMID- 17194134
TI  - Simultaneous maximization of cell permeabilization and viability in single-cell
      electroporation using an electrolyte-filled capillary.
AB  - A549 cells were briefly exposed to Thioglo-1, which converts thiols to
      fluorescent adducts. The fluorescent cells were exposed to short (50-300 ms)
      electric field pulses (500 V across a 15 cm capillary) created at the tip of an
      electrolyte-filled capillary. Fluorescence microscopy revealed varying degrees of
      cell permeabilization depending on the conditions. Longer pulses and a shorter
      cell-capillary tip distance led to a greater decrease in the cell's fluorescence.
      Live/dead (calcein AM and propidium iodide) testing revealed that a certain
      fraction of cells died. Longer pulses and shorter cell-capillary tip distances
      were more deadly. An optimum condition exists at a cell-capillary tip distance of
      3.5-4.5 microm and a pulse duration of 120-150 ms. At these conditions, >90% of
      the cells are permeabilized and 80-90% survive.

PMID- 17194136
TI  - Probing the responsive behavior of polyelectrolyte brushes using electrochemical
      impedance spectroscopy.
AB  - Cyclic voltammetry and impedance spectroscopy were employed to probe the
      responsive properties of polyelectrolyte brushes. Poly[(dimethylamino)ethyl
      methacrylate] (PDMAEMA) brushes over 100 nm thick on gold substrates were
      synthesized via surface-initiated atom-transfer radical polymerization and
      quaternized with methane iodide to obtain cationic brushes (Q-PDMAEMA). Q-PDMAEMA
      brushes respond to electrolytes by exhibiting swollen and collapsed states.
      Swollen brushes allow good permeability of electroactive probes, while collapsed
      states block electron transport. Electrolytes have different impacts on the
      electrochemical properties of Q-PDMAEMA. Some salts (NaNO3) cause brush collapse
      due to charge screening, while others such as those with more hydrophobic anions
      (ClO4-, PF6-, and Tf2N-) induce brush collapse because of solubility changes. The
      collapsed brushes exhibit intrinsically different resistance as probed with
      impedance. Charged screened brushes retain good permeability to electroactive
      probes. Strongly coordinating hydrophobic anions lead to insoluble brushes,
      resulting in a high resistance. These results show that electrochemical impedance
      spectroscopy is a powerful technique to probe the properties and structure of
      polyelectrolyte brushes.

PMID- 17194137
TI  - Differentiation of domains in composite surface structures by charge-contrast X
      ray photoelectron spectroscopy.
AB  - An external bias is applied to two samples containing composite surface
      structures, while recording an XPS spectrum. Altering the polarity of the bias
      affects the extent of differential charging in domains that are chemically or
      electronically different to create a charge contrast. By utilizing this charge
      contrast, we show that two distinct silicon nitride and silicon oxynitride
      domains are present in one of the composite samples. Similarly, we use this
      technique to show that titanium oxide and silicon oxide domains exist as separate
      chemical entities in another composite sample.

PMID- 17194138
TI  - Electrode surface confinement of self-assembled enzyme aggregates using magnetic
      nanoparticles and its application in bioelectrocatalysis.
AB  - Self-assembled enzyme aggregates, prepared from magnetic iron oxide
      nanoparticles, avidin, and a biotinylated redox enzyme, were shown particularly
      useful for the simple, fast, and efficient construction of highly enzyme-loaded
      electrodes with the help of a magnet. The approach was illustrated in the case of
      the bioelectrocatalytic oxidation of NADH by a diaphorase oxidoreductase in the
      presence of a ferrocene mediator. Two different self-assembling procedures were
      tested, taking advantage of the spontaneous aggregation of the nanoparticles in
      the presence of avidin and also of the multivalency binding of biotinylated
      diaphorase toward avidin. Activities of the bound and unbound diaphorase were
      systematically controlled allowing determination of the number of active
      biotinylated diaphorase per nanoparticle incorporated within each magnetic enzyme
      aggregate. An active enzyme loading capacity of up to 2.35 nmol mg-1 was found
      for the best nanostructured enzyme assembly, which is 200 times better than for
      commercialized magnetic micrometer-sized beads coated with streptavidin and
      saturated with diaphorase. With the help of a permanent magnet, the magnetic
      enzyme aggregates were finally magnetically collected as a film on the surface of
      a small screen-printed carbon electrode and the catalytic currents recorded by
      cyclic voltammetry. From the analysis of the steady-state catalytic current
      responses and the kinetic rate constants of biotinylated diaphorase, it was
      possible to determine the enzyme concentration within the magnetic films. Owing
      to the high enzyme loading in the aggregates of nanoparticles (i.e., 130 microM),
      the catalytic current responses were definitely higher than the ones measured at
      an electrode coated with a closed-packed monolayer of diaphorase or at an
      electrode covered with a film of magnetic micrometer-sized streptavidin beads
      saturated with diaphorase.

PMID- 17194139
TI  - Semihydrodynamic injection for high salt stacking and sweeping on microchip
      electrophoresis and its application for the analysis of estrogen and estrogen
      binding.
AB  - In this work, a semihydrodynamic (SHD) injection method was introduced and
      coupled with high salt stacking and electrokinetic chromatography for the
      analysis of estrogen and estrogen binding using a simple cross microchannel. The
      SHD method allows all samples to be hydrodynamically injected and focused into
      the separation channel at a relatively high flow rate and without splitting and
      diffusion, leading to reproducible bias-free injections of larger sample volumes
      (up to 50 nL) within 3 s. Moreover, the injection method is initiated without
      voltage switching, leading to a reduced mixing effect. Such advantages are well
      suited for performing stacking and sweeping on a microchip. We investigated the
      stacking effect under continuous and discontinuous co-ion conditions as well as
      under sweeping conditions. Micellar sweeping effect alone was relatively weak (7
      8 times), partly due to a lower sodium cholate concentration (30 mM) used for the
      running buffer. By combining the sweeping effect with high salt stacking,
      however, up to a 200-300-fold enhancement factor could be achieved, and the high
      salt and low-surfactant contents for the running buffer were favorable for
      binding study under nonequilibrium conditions. To the best of our knowledge, this
      is the first demonstration of the hydrodynamic injection used for high salt
      sample stacking on a microchip, also for further combining micellar
      electrochromatography and affinity separation for the analysis of hydrophobic
      ligand binding using microchip electrophoresis.

PMID- 17194140
TI  - Simultaneous in situ reflectance and probe beam deflection measurements at solid
      electrode-aqueous electrolyte interfaces.
AB  - A method is herein described for performing simultaneous in situ normal incidence
      reflectance spectroscopy (DeltaR/R, lambda = 633 nm) and probe beam deflection
      (PBD) measurements at solid electrodes in aqueous electrolytes, while scanning
      the potential linearly between two prescribed limits. Results obtained for Au in
      0.1 M HClO4 and for Pt in both 0.1 M HClO4 and 0.1 M NaOH were found to be in
      excellent agreement with those reported in the literature for each individual
      spectroelectrochemical technique under otherwise similar conditions. Data
      collected for Pt electrodes in CO-saturated 0.1 M HClO4 revealed rather sudden
      changes in both DeltaR/R and PBD signals in the voltammetric region where the
      characteristic sharp peak associated with the oxidation of adsorbed CO occurs.
      This behavior was ascribed, respectively, to oxide formation (DeltaR/R) and to
      changes in the electrolyte composition in region neighboring the electrode,
      involving predominantly the acid concentration (PBD). In contrast, CO oxidation
      on Pt in 0.1 M NaOH yielded a PBD response consistent with formation of solution
      phase carbonate via the reaction of the product, CO2, with hydroxyl ion. The
      exquisite sensitivity of DeltaR/R and PBD to interfacial phenomena was further
      illustrated using a monolayer of hemin irreversibly adsorbed on glassy carbon
      surfaces in 0.1 M Na2B4O7 (pH approximately 9.2). For this system, DeltaR/R was
      found to be proportional to the relative fractions of hemin and its reduced
      counterpart, while the PBD signal could be correlated with corresponding
      variations in the electrolyte concentration induced by the surface-bound redox
      process.

PMID- 17194141
TI  - Luminescent quantum dots fluorescence resonance energy transfer-based probes for
      enzymatic activity and enzyme inhibitors.
AB  - The paper describes the development and characterization of analytical properties
      of quantum dot-based probes for enzymatic activity and for screening enzyme
      inhibitors. The luminescent probes are based on fluorescence resonance energy
      transfer (FRET) between luminescent quantum dots that serve as donors and
      rhodamine acceptors that are immobilized to the surface of the quantum dots
      through peptide linkers. Peptide-coated CdSe/ZnS quantum dots were prepared using
      a one-step ligand exchange process in which RGDC peptide molecules replace
      trioctylphosphine oxide (TOPO) molecules as the capping ligands of the quantum
      dots. The peptide molecules were bound to the surface of the CdSe/ZnS quantum
      dots through the thiol group of the peptide cysteine residue. The peptide-coated
      quantum dots were labeled with rhodamine to form the FRET probes. The emission
      quantum yield of the quantum dot FRET probes was 4-fold lower than the emission
      quantum yield of TOPO-capped quantum dots. However, the quantum dot FRET probes
      were sufficiently bright to enable quantitative enzyme and enzyme inhibition
      assays. The probes were used first to test the enzymatic activity of trypsin in
      solution based on FRET signal changes of the quantum dot-based enzymatic probes
      in the presence of proteolytic enzymes. For example, exposure of the quantum dot
      FRET probes to 500 microg/mL trypsin for 15 min resulted in 60% increase in the
      photoluminescence of the quantum dots and a corresponding decrease in the
      emission of the rhodamine molecules. These changes resulted from the release of
      rhodamine molecules from the surface of the quantum dots due to enzymatic
      cleavage of the peptide molecules. The quantum dot FRET-based probes were used to
      monitor the enzymatic activity of trypsin and to screen trypsin inhibitors for
      their inhibition efficiency.

PMID- 17194142
TI  - Monitoring the electroosmotic flow in capillary electrophoresis using contactless
      conductivity detection and thermal marks.
AB  - The fundamental aspects and the capillary electrophoresis usage of thermal marks
      are presented. The so-called thermal mark is a perturbation of the electrolyte
      concentration generated by a punctual heating of the capillary while the
      separation electric field is maintained. The heating pulse is obtained by
      powering tungsten filaments or surface mount device resistors with 5 V during a
      few tens to hundreds of milliseconds. In the proposed model, the variation of the
      transport numbers with the rising temperature leads to the formation of low- and
      high-concentration regions during the heating. After cooling down, the initial
      mobilities of the species are restored and these regions (the thermal mark)
      migrate chiefly due to the electroosmotic flow (EOF). The mark may be recorded
      with a conductivity detector as part of a usual electropherogram and be used to
      index the analyte peaks and thus compensate for variations of the EOF. In a
      favorable case, 10 mmol/L KCl solution, the theory suggests that the error in the
      measurement of EOF mobility by this mean is only -6.5 x 10(-7) cm2 V-1 s-1. The
      method was applied to the analysis of alkaline ions in egg white, and the
      relative standard deviations of the corrected mobilities of these ions were
      smaller than 1%. This is a challenging matrix, because albumin reduces the EOF to
      20% of its initial value after 11 runs. The combination of thermal mark,
      electrolysis separated, and contactless conductivity detection allowed the
      measurement of the EOF of a silica capillary with unbuffered KCl solution with
      constant ionic strength. The overall approach is advantageous, because one can
      easily control the chemical composition of the solution in contact with the inner
      surface of the capillary.

PMID- 17194144
TI  - Aptamer-based electrochemical detection of picomolar platelet-derived growth
      factor directly in blood serum.
AB  - We report an electrochemical, aptamer-based (E-AB) sensor for the detection of
      platelet-derived growth factor (PDGF) directly in blood serum. The E-AB approach
      employs alternating current voltammetry to monitor target-induced folding in a
      methylene blue-modified, PDGF-binding aptamer. The sensor is sensitive, highly
      selective, and essentially reagentless: we readily detect the BB variant of PDGF
      at 1 nM directly in undiluted, unmodified blood serum and at 50 pM (1.25 ng/mL)
      in serum-diluted 2-fold with aqueous buffer. The sensitivity and selectivity
      achieved by this sensor match or significantly exceed those of the best analogous
      optical approaches. For example, the detection limit attained in 50% serum is
      achieved against a >25 million-fold excess of contaminating blood proteins and
      represents a 4 order of magnitude improvement over the most sensitive optical
      PDGF aptasensor reported to date. Moreover, the E-AB sensor combines these
      promising attributes in a platform that is reusable, label-free, and electronic.
      Given these advantages, E-AB sensors appear well suited for implementation in
      portable microdevices directed at the direct detection of proteins and small
      molecules in complex, largely unprocessed clinical samples.

PMID- 17194145
TI  - Constrained regularization: hybrid method for multivariate calibration.
AB  - We present a hybrid multivariate calibration method, constrained regularization
      (CR), and demonstrate its utility via numerical simulations and experimental
      Raman spectra. In this new method, multivariate calibration is treated as an
      inverse problem in which an optimal balance between model complexity and noise
      rejection is achieved with the inclusion of prior information in the form of a
      spectral constraint. A key feature is that the constraint is incorporated in a
      flexible manner, allowing the minimization algorithm to arrive at the optimal
      solution. We demonstrate that CR, when used with an appropriate constraint, is
      superior to methods without prior information, such as partial least-squares, and
      is less susceptible to spurious correlations. In addition, we show that CR is
      more robust than methods in which the constraint is rigidly incorporated, such as
      hybrid linear analysis, when the exact spectrum of the analyte of interest as it
      appears in the sample is not available. This situation can occur as a result of
      experimental or sample variations and often arises in complex or turbid samples
      such as biological tissues.

PMID- 17194143
TI  - Vortex-trap-induced fusion of femtoliter-volume aqueous droplets.
AB  - This paper describes the use of an optical vortex trap for the transport and
      fusion of single femtoliter-volume aqueous droplets. Individual droplets were
      generated by emulsifying water in acetophenone with SPAN 80 surfactant. We
      demonstrate the ability of optical vortex traps to position trapped droplets
      precisely while excluding surrounding aqueous droplets from entering the trap,
      thereby preventing unwanted cross contamination by other nearby droplets.
      Additionally, the limitation of optical vortex traps for inducing droplet fusion
      is illustrated, and a remedy is provided through modulation of the spatial
      intensity profile of the optical vortex beam. Spatial modulation was achieved by
      translating the computer-generated hologram (CGH) with respect to the input
      Gaussian beam, thereby shifting the location of the embedded phase singularity
      (dark core) within the optical vortex beam. We present both simulated and
      experimentally measured intensity profiles of the vortex beam caused by
      translation of the CGH. We further describe the use of this technique to achieve
      controlled and facile fusion of two aqueous droplets.

PMID- 17194147
TI  - Application of ganglioside-sensitized liposomes in a flow injection
      immunoanalytical system for the determination of cholera toxin.
AB  - Cholera, an acute infectious disease associated with water and seafood
      contamination, is caused by the bacterium Vibrio cholerae, which lives and
      colonizes in the small intestine and secretes cholera toxin (CT), a causative
      agent for diarrhea in humans. Based on earlier lateral flow assays, a flow
      injection liposome immunoanalysis (FILIA) system with excellent sensitivity was
      developed in this study for the determination of CT at zeptomole levels.
      Ganglioside (GM1), found to have specific affinity toward CT, was inserted into
      the phospholipid bilayer during the liposome synthesis. These GM1-sensitized,
      sulforhodamine B (SRB) dye-entrapping liposomes were used as probes in the FILIA
      system. Anti-CT antibodies were immobilized in its microcapillary. CT was
      detected by the formation of a sandwich complex between the immobilized antibody
      and GM1 liposomes. During the assay, the sample was introduced first into the
      column, and then liposomes were injected to bind to all CT captured by the
      antibody in the microcapillary. Subsequently, the SRB dye molecules were released
      from the bound liposomes via the addition of the detergent octyl glucopyranoside.
      The released dye molecules were transported to a flow-through fluorescence
      detector for quantification. The FILIA system was optimized with respect to flow
      rate, antibody concentration, liposome concentration, and injected sample volume.
      The calibration curve for CT had a linear range of 10-16 to 10-14 g mL-1. The
      detection limit of this immunosensor was 6.6 x 10(-17) g mL-1 in 200-microL
      samples (equivalent to 13 ag or 1.1 zmol).

PMID- 17194146
TI  - Polypyrrole-based optical probe for a hydrogen peroxide assay.
AB  - An optical sensing probe has been developed by taking advantage of the
      polypyrrole (PPy) chromophore. The absorbance of the oxidation product of
      pyrrole, i.e., solubilized PPy colloids, is shown to be directly proportional to
      the concentration of hydrogen peroxide, when H2O2 is used as an oxidant for
      pyrrole in the presence of a surfactant, sodium dodecyl sulfate, and Fe(II) in a
      slightly acidic aqueous solution. Based on this result, a new optical sensing
      method has been developed for the determination of H2O2. The probe has also been
      applied to optical sensing of ethanol by biocatalyzed generation of H2O2 in the
      presence of O2, ethanol, and alcohol oxidase. The novel methodology is expected
      to provide a general protocol for the determination of H2O2 as well as for
      numerous other oxidase-based reactions producing H2O2 as a product.

PMID- 17194148
TI  - Piezoelectric quartz crystal microbalance sensor for trace aqueous cyanide ion
      determination.
AB  - Using selective reaction chemistry, our present research has developed an online,
      real-time sensor capable of monitoring toxic cyanide at both drinking water
      standard and environmental regulatory concentrations. Through the use of a flow
      cell, aqueous samples containing cyanide are reacted with a gold electrode of a
      piezoelectric crystal to indirectly sense cyanide concentration by the
      dissolution of metallic gold. The quartz crystal is an AT-cut wafer sandwiched
      between two neoprene O-rings within the liquid flow cell. The presence of cyanide
      in solution results in the selective formation of a soluble dicyano-gold complex
      according to the Elsner reaction: 4Au + 8CN- + 2H2O + O2 <=> 4Au(CN)2- + 4OH-.
      The resulting loss of gold from the electrode is detected by the piezoelectric
      crystal as a resonant frequency change. Since free cyanide is a weak acid (pKa =
      9.3), available protons compete for cyanide ligands. Therefore, increased sample
      pH provides higher sensitivity. The detection limits at pH 12 are 16.1 and 2.7
      ppb for analysis times of 10 min and 1 h, respectively. The incorporation of the
      flow cell improves both analyte sensitivity and instrument precision, with an
      average signal intensity drift of only 5% over a 2-h analysis. The calibrations
      show excellent linearity over a variety of cyanide concentrations ranging from
      low ppb to hundreds of ppm. This detection method offers the advantage of
      selectively detecting cyanides posing a biohazard while avoiding detection of
      stable metal cyanides. This aspect of the system is based on competitive exchange
      of available metals and gold with cyanide ligands. Stable metal cyanide complexes
      possess a higher formation constant than cyanoaurate. This detection system has
      been configured into a flow injection analysis array for simple adaptation to
      automation. Anions commonly found in natural waters have been examined for
      interference effects. Additionally, the sensor is free from interference by
      aqueous cyanide analogues including thiocyanate. The developed detection system
      provides rapid cyanide determinations with little sample preparation or
      instrument supervision.

PMID- 17194149
TI  - Molecularly imprinted solid-phase extraction of diazepam and its metabolites from
      hair samples.
AB  - An anti-diazepam, molecularly imprinted polymer (MIP) has been synthesized and
      used to extract diazepam and other benzodiazepines from hair samples via a
      molecularly imprinted solid-phase extraction (MISPE) protocol. Optimum retention
      of diazepam on the MIP columns was achieved using an apolar solvent, and the
      binding capacity of the polymer toward diazepam was found to be 110 ng of
      diazepam/mg of polymer. The recovery of a 50 ng diazepam standard spiked into
      blank hair was 93%, with good precision (RSD = 1.5%). The LOD and LOQ of diazepam
      in spiked hair samples were 0.09 and 0.14 ng/mg, respectively. The MISPE method
      was demonstrated to be applicable to the analysis of diazepam metabolites and
      other benzodiazepine drugs, in addition to diazepam itself. The application of
      the extraction method to postmortem hair samples yielded results that were in
      good agreement with the corresponding ELISA data (from blood samples) and data
      arising from the analysis of the same blood samples using a validated in-house
      SPE-LC-MS-MS method.

PMID- 17194150
TI  - Quantification of diacylglycerol species from cellular extracts by electrospray
      ionization mass spectrometry using a linear regression algorithm.
AB  - Diacylglycerols (DAGs) play significant roles in both intermediate metabolism and
      signal transduction. These lipid species are second messengers involved in
      modulating a plethora of cellular processes. Evaluation of DAG species
      concentrations has been hampered by the lack of a reliable method for molecular
      species analysis within a complex mixture of cellular lipids. We describe a new
      method for quantitative analysis of DAG species from complex biological extracts
      based on positive mode electrospray ionization mass spectrometry without prior
      derivatization. Quantification is achieved using internal standards and
      calibration curves constructed by spiking cell extracts with different
      concentrations of DAG species containing various acyl chain lengths and degrees
      of unsaturation. The new mass spectral data processing algorithm incorporates a
      multiple linear regression model including a factor accountable for possible
      interactions between experimental preparations and the slope of the curve for the
      standards, allowing the examinations of the effects of sample origin conditions
      (such as cell types, phenotypes, etc.) and instrument variability on this slope.
      Internal standards provide a basis for quantification of 28 DAG molecular species
      detected in RAW 264.7 cells after stimulation of a G-protein coupled receptor
      with platelet activating factor. This method displays excellent reproducibility
      over the established range of concentrations with variations of < or =10% and is
      highly sensitive with a detection limit of 0.1-0.4 pmol/microL depending upon
      acyl chain composition. We have shown differential effects on various DAGs in
      response to a ligand which illustrates the importance of examining lipids at the
      molecular species level rather than as a single homogeneous entity.

PMID- 17194152
TI  - Laser microprobe with fourier transform ion cyclotron resonance mass spectrometer
      for surface analysis.
AB  - Fourier transform ion cyclotron resonance laser microprobe mass spectrometry
      (FTICR LMMS) uses focused laser irradiation of solids with a spot of 5 microm and
      a FTICR mass analyzer for local analysis with high mass resolution. A new ion
      source design has been developed to improve the extraction and transfer of ions
      generated in an external laser microprobe source. Calculations predicted trapping
      of ions initially emitted with angles up to 40 degrees and 60 degrees from the
      surface and from a distance of 1 mm above the sample, respectively. The
      analytical performances of the method have been verified on two sets of test
      samples. First, detection of chemisorbed benzotriazole on copper, average of two
      monolayers, has been shown with less sample consumption than typically required
      in static secondary ion mass spectrometry with a time-of-flight analyzer. Second,
      experiments on a thermal plate for offset printing have shown the feasibility of
      analysis and quantification of dyes embedded in a polymer matrix.

PMID- 17194151
TI  - Affinity capture and detection of immunoglobulin E in human serum using an
      aptamer-modified surface in matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Capture and detection of immunoglobulin E (IgE) in simple solution and in human
      serum using an aptamer-modified probe surface for affinity matrix-assisted laser
      desorption/ionization mass spectroscopy detection is reported. Detectable signals
      were obtained for 1 amol of IgE applied either in a single, 1microL application
      of 1 pM IgE or after 10 successive, 1-microL applications of 100 fM IgE. In both
      cases, the surface was rinsed after each application of IgE to remove sample
      concomitants including salts and free or nonspecifically associated proteins.
      Detection of native IgE, which is the least abundant of the serum immunoglobulins
      and occurs at subnanomolar levels, in human serum was demonstrated and
      interference from the high-abundance immunoglobulins and albumin was
      investigated. The aptamer-modified surface showed high selectivity toward
      immunoglobulins in serum, with no significant interference from serum albumin.
      Addition of IgE to the serum suppressed the signals from the other
      immunoglobulins, confirming the expected selectivity of the aptamer surface
      toward IgE. Dilution of the serum increased the selectivity toward IgE; the
      protein was detected without interference in a 10,000-fold dilution of the serum,
      which is consistent with detection of IgE at amol (pM) levels in standard
      solutions.

PMID- 17194153
TI  - Thermal modulation voltammetry with laser heating at an aqueous|nitrobenzene
      solution microinterface: determination of the standard entropy changes of
      transfer for tetraalkylammonium ions.
AB  - Thermal modulation voltammetry (TMV) with laser heating was successfully
      performed at an aqueous|nitrobenzene (NB) solution microinterface, by taking
      advantage of the fact that laser light with a wavelength of 325.0 nm is optically
      transparent to the aqueous solution but opaque to the NB solution. When the laser
      beam impinges upon the interface from the aqueous solution side, a temperature is
      raised around the interface through the thermal diffusion subsequent to the light
      to-heat conversion following the optical absorption by the NB solution near the
      interface. Based on such a principle, we achieved a fluctuating temperature
      perturbation around the interface for TMV by periodically irradiating the
      interface with the laser beam. On the other hand, the fluctuating temperature
      perturbation has influence on currents for transfer of an ion across the
      interface to produce fluctuating currents synchronized with the perturbation
      through temperature coefficients of several variables concerning the transfer,
      such as the standard transfer potential and the diffusion coefficient of the ion.
      Consequently, TMV has the possibility of providing information about the standard
      entropy change of transfer corresponding to a temperature coefficient of the
      standard transfer potential and a temperature coefficient of the diffusion
      coefficient. In this work, the aqueous|NB solution interface of 30 microm in
      diameter was irradiated with the laser beam at 10 Hz, and the currents
      synchronized with the periodical irradiation were recorded as a function of the
      potential difference across the interface in order to construct a TM
      voltammogram. TM voltammograms were measured for transfer of tetramethylammonium,
      tetraethylammonium, tetrapropylammonium, and tetra-n-butylammonium ions from the
      aqueous solution to the NB solution, and the standard entropy change of transfer
      was determined for each ion, according to an analytical procedure based on a
      mathematical expression of the TM voltammogram. Comparison of the values obtained
      in this work with the literature values has proved that TMV with laser heating is
      available for the determination of the standard entropy change of transfer for an
      ion.

PMID- 17194154
TI  - Preparation of superparamagnetic ribonuclease A surface-imprinted submicrometer
      particles for protein recognition in aqueous media.
AB  - Superparamagnetic ribonuclease A surface-imprinted polymeric particles that can
      preferentially bind the template protein in an aqueous environment were prepared
      in this study. Methyl methacrylate and ethylene glycol dimethacrylate were
      employed as the functional and cross-linker monomers, respectively. Regularly
      shaped submicrometer (700-800 nm) particles imprinted with ribonuclease A were
      successfully prepared using redox-initiated miniemulsion polymerization.
      Nanosized Fe3O4 magnetite was encapsulated in the imprinted particles with good
      encapsulation efficiency (17.5 wt %) for the incorporation of the
      superparamagnetic property. Good selectivity toward the template over the control
      protein in an aqueous environment was demonstrated by the imprinted particles in
      the batchwise and competitive rebinding tests with the highest template loading,
      Qmax, of 127.7 mg/g observed in the batch rebinding test. Given the small sizes
      of the imprinted particles and the presence of the binding sites on the surface,
      the rebinding process was kinetically favorable despite the sheer bulk of the
      macromolecules. In the desorption study, it was found that the more hydrophobic
      solvent was more effective for ribonuclease A desorption from the imprinted
      particles. This indicated that the hydrophobic effect was probably the main form
      of interaction responsible for the template rebinding to the imprinted sites in
      an aqueous media.

PMID- 17194155
TI  - Identification of pesticide transformation products in food by liquid
      chromatography/time-of-flight mass spectrometry via "fragmentation-degradation"
      relationships.
AB  - The identification of transformation products of pesticides in foodstuffs is a
      crucial task difficult to tackle, due to the lack of standards and scarce
      information available. In this work, we describe a methodology for the
      identification and structural elucidation of pesticide transformation products in
      food. The proposed strategy is based on the use of liquid chromatography
      electrospray time-of-flight mass spectrometry (LC/TOFMS): accurate mass
      measurements of (molecule and fragment) ions of interest are used in order to
      establish relationships between fragmentation of the parent pesticides in the
      instrument (in-source CID fragmentation) and possible degradation products of
      these pesticides in food. Examples of this strategy showing the potential of
      LC/TOFMS to determine unknown pesticides in food are described in two different
      real samples, suggesting that pesticides often are transformed into degradation
      products in the same fashion that they are fragmented in the instrument. Using
      the proposed approach and without using standards a priori, based solely on
      accurate mass measurements of ions and "fragmentation-degradation" relationships,
      we have identified two parent pesticides (amitraz and malathion) along with six
      degradation products, m/z 253 (N,N'-bisdimethylphenylformamidine), 163 (N-2,4
      dimethylphenyl-N-methyl formamidine), 150 (2,4-dimethylformamidine), and 122 (2,4
      dimethylaniline) from amitraz, and m/z 317 and 303, due to ether hydrolysis of
      methyl and ethyl groups from malathion. Structures for these species were
      proposed, and the potential of the proposed approach was critically discussed.

PMID- 17194156
TI  - Derivatization with Girard reagent T combined with LC-MS/MS for the sensitive
      detection of 5-formyl-2'-deoxyuridine in cellular DNA.
AB  - Nucleoside 5-formyl-2'-deoxyuridine (FodU) is a major thymidine lesion generated
      by reactive oxygen species. In vitro and in vivo replication studies revealed
      that FodU can be mutagenic. A reliable and sensitive quantification method is,
      therefore, important for assessing the biological implications of this lesion.
      However, the detection limit of FodU by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) was relatively poor compared with those of other
      oxidative DNA base damages. In this paper we described a new approach for the
      highly sensitive detection of FodU. We derivatized FodU with Girard reagent T to
      form a hydrazone conjugate harboring a precharged quaternary ammonium moiety,
      which enabled the facile detection of the resulting conjugate by positive-ion
      electrospray ionization MS. We also showed that the combination of derivatization
      with LC-MS/MS on a linear-ion-trap mass spectrometer could allow for the
      quantification of FodU at a detection limit of 3-4 fmol, which is approximately
      20-fold better than that for the direct analysis of the underivatized compound.
      By using isotope-labeled FodU as the internal standard and this derivatization
      method, we further quantified, by using LC-MS/MS, the yield of FodU formed in
      cellular DNA.

PMID- 17194158
TI  - Assessing the macroporous structure of monolithic columns by transmission
      electron microscopy.
AB  - A set of monolithic stationary phases representing a broad span of monomers and
      porogens have been characterized directly in their capillary chromatographic
      format by computational assessment of their pore structure from transmission
      electron micrographs obtained after in situ embedment of the monoliths in
      contrast resin, followed by dissolution of the fused-silica tubing, further
      encasement of the resin-embedded monolith, and microtomy. This technique has been
      compared to mercury intrusion, a more conventional technique for macroporosity
      estimation. Supplementing the embedding resin by lead methacrylate gave a
      negative staining, and the resulting micrographs showed a good contrast between
      the polymeric monoliths and the embedding resin that allowed studies on the pore
      formation and polymer development. The technique was also applied to a commercial
      monolithic silica column.

PMID- 17194159
TI  - Detection of 100 aM fluorophores using a high-sensitivity on-chip CE system and
      transient isotachophoresis.
AB  - We present a highly sensitive capillary electrophoresis (CE) assay that combines
      transient, single-interface on-chip isotachophoresis (ITP) and a laser-induced
      confocal fluorescence detection setup. We performed experimental parametric
      studies to show the effects of microscope objective specifications and intensity
      of excitation laser on optimization of a high-sensitivity on-chip CE detection
      system. Using the optimized detection system, single-molecule detection of Alexa
      Fluor 488 was demonstrated, and signal data were validated with autocorrelation
      analysis. We also demonstrated a separation and detection of 100 aM fluorophores
      (Alexa Fluor 488 and bodipy) in a fast assay using a high-sensitivity on-chip CE
      detection system and an ITP/CE protocol with no manual buffer exchange steps.
      This is, to the knowledge of the authors, the highest electrophoretic separation
      sensitivity ever reported.

PMID- 17194157
TI  - Porous SiO2 interferometric biosensor for quantitative determination of protein
      interactions: binding of protein A to immunoglobulins derived from different
      species.
AB  - Determination of kinetic and thermodynamic protein binding constants using
      interferometry from a porous Si Fabry-Perot layer is presented. A protein A
      capture probe is adsorbed within the pores of an oxidized porous Si matrix, and
      binding of immunoglobulin G (IgG) antibodies derived from different species is
      investigated. The relative protein A/IgG binding affinity is human > rabbit >
      goat, in agreement with literature values. The equilibrium binding constant (Ka)
      for human IgG binding to surface-immobilized protein A is determined to be (3.0
      +/- 0.5) x 107 M-1 using an equilibrium Langmuir model. Kinetic rate constants
      are calculated to be kd = (2.1 +/- 0.2) x 10-4 s-1 and ka = (1.2 +/- 0.4) x 104 M
      1 s-1 using nonlinear least-squares analysis, yielding an equilibrium binding
      constant of Ka = (5.5 +/- 1.5) x 107 M-1. Both steady-state and time-dependent
      measurements yield equilibrium binding constants that are consistent with
      literature values. Kinetic rate constants determined through nonlinear least
      squares analysis are also in agreement with protein A/IgG binding on a surface.
      Dosing with a high concentration of analyte leads to deviations from ideal
      binding behavior, interpreted in terms of restricted analyte diffusion within the
      porous SiO2 matrix. It is shown that the diffusion limitations can be minimized
      if the kinetic measurements are performed at low analyte concentrations or under
      conditions in which the protein A capture probe is not saturated with analyte.
      Potential limitations of the use of porous SiO2 interferometers for quantitative
      determination of protein binding constants are discussed.

PMID- 17194160
TI  - Self-assembled layer of thiolated protein G as an immunosensor scaffold.
AB  - In this study, our goal was to produce a self-assembled layer on a gold electrode
      that would enable the capture of antibodies orientated for maximum binding to
      their specific antigen in an immunosensor. To achieve this, the amine groups from
      lysine residues in protein G were initially converted to thiol groups with 2
      iminothiolane. The high affinity of thiols for a gold surface facilitates the
      direct formation of a self-assembled protein G layer. Following this, the coated
      gold electrode was exposed to a solution of capture antibody (mAb1) so that these
      antibodies could attach to the protein G layer through their nonantigenic
      regions, leaving antigen binding sites available with minimal steric hindrance
      for binding of target analyte. A comparative study between this method and the
      more conventional strategy of covalently attaching a layer of nonthiolated
      protein G on an alkanethiol self-assembled monolayer-coated gold electrode has
      been performed. Based on a reduced preparation time, and an enhanced capacity for
      immobilized capture antibody to bind its target analyte due to a more favorable
      orientation, the layer of thiolated protein G was found to be a more suitable
      backbone for an electrochemical immunosensor.

PMID- 17194161
TI  - Pronase-immobilized enzyme reactor: an approach for automation in glycoprotein
      analysis by LC/LC-ESI/MSn.
AB  - An automated analytical approach is proposed for simultaneous characterization of
      glycan and peptide moieties in pronase-generated glycopeptides. The proposed
      method is based on the use of a new pronase-immobilized enzyme reactor for the on
      line rapid digestion of the target glycoprotein. By coupling the bioreactor to a
      Hypercarb chromatographic trap column, on-line selective glycopeptide enrichment
      prior to normal-phase liquid chromatography-mass spectrometry was obtained. A
      detailed study was carried out for integration and automation of each phase of
      the proposed analytical procedure. On-line digestion allowed extensive cleavage
      of the model protein (ribonuclease B), yielding to glycopeptides with peptide
      moieties up to eight amino acids, carrying the Man5-Man9 N-glycans each,
      selectively resolved on an Amide-80 column. The use of a linear ion trap
      instrument resulted in efficient ion capture and led to MS3 acquisition times and
      spectra quality similar to those for MS2, allowing the unambiguous identification
      of glycan (MS2) and peptide (MS3) sequences. The proposed procedure reduces the
      glycoprotein analysis time from approximately 3 days, as in most of the
      traditional off-line methods, to approximately 1 h.

PMID- 17194162
TI  - Facile hyphenation of gas chromatography and a microcantilever array sensor for
      enhanced selectivity.
AB  - The very simple coupling of a standard, packed-column gas chromatograph with a
      microcantilever array (MCA) is demonstrated for enhanced selectivity and
      potential analyte identification in the analysis of volatile organic compounds
      (VOCs). The cantilevers in MCAs are differentially coated on one side with
      responsive phases (RPs) and produce bending responses of the cantilevers due to
      analyte-induced surface stresses. Generally, individual components are difficult
      to elucidate when introduced to MCA systems as mixtures, although pattern
      recognition techniques are helpful in identifying single components, binary
      mixtures, or composite responses of distinct mixtures (e.g., fragrances). In the
      present work, simple test VOC mixtures composed of acetone, ethanol, and
      trichloroethylene (TCE) in pentane and methanol and acetonitrile in pentane are
      first separated using a standard gas chromatograph and then introduced into a MCA
      flow cell. Significant amounts of response diversity to the analytes in the
      mixtures are demonstrated across the RP-coated cantilevers of the array.
      Principal component analysis is used to demonstrate that only three components of
      a four-component VOC mixture could be identified without mixture separation.
      Calibration studies are performed, demonstrating a good linear response over 2
      orders of magnitude for each component in the primary study mixture. Studies of
      operational parameters including column temperature, column flow rate, and array
      cell temperature are conducted. Reproducibility studies of VOC peak areas and
      peak heights are also carried out showing RSDs of less than 4 and 3%,
      respectively, for intra-assay studies. Of practical significance is the facile
      manner by which the hyphenation of a mature separation technique and the
      burgeoning sensing approach is accomplished, and the potential to use pattern
      recognition techniques with MCAs as a new type of detector for chromatography
      with analyte-identifying capabilities.

PMID- 17194163
TI  - Measurements of surface tension of organic solvents using a simple
      microfabricated chip.
AB  - Measurement of the surface tension of organic solvents using a simple
      microfabricated chip was developed based on the principle of differential
      capillary rise. The theory, design, fabrication, and characterization of the chip
      were described. A two-step etching technique was used to fabricate a number of
      microchannels with different dimensions on the glass substrate. Capillarity was
      used to introduce liquid samples, which requires no power supply or actuator to
      be applied in the experiment. Liquid in different microchannels generated
      capillary rise with different heights, by which surface tension maybe calculated.
      Seven common organic solvents, ethanol, acetone, acetonitrile, dichloromethane,
      hexane, methanol, and toluene, were tested at room temperature. The surface
      tension of ethanol at different temperatures was measured over the range of 5-45
      degrees C. Relative standard deviation for seven replicate measurements at each
      temperature is 0.20-0.74%. The results showed good reproducibility and acceptable
      precision compared with traditional methods. Very low reagent consumptions and
      short analysis time were achieved using this simple method.

PMID- 17194164
TI  - Identification of A/H5N1 influenza viruses using a single gene diagnostic
      microarray.
AB  - In previous work, a simple diagnostic DNA microarray that targeted only the
      matrix gene segment of influenza A (MChip) was developed and evaluated with
      patient samples. In this work, the analytical utility of the MChip for detection
      and subtyping of an emerging virus was evaluated with a diverse set of A/H5N1
      influenza viruses. A total of 43 different highly pathogenic A/H5N1 viral
      isolates that were collected from diverse geographic locations, including
      Vietnam, Nigeria, Indonesia, and Kazakhstan, representing human, feline, and a
      variety of avian infections spanning the time period 2003-2006 were used in this
      study. A probabilistic artificial neural network was developed for automated
      microarray image interpretation through pattern recognition. The microarray assay
      and subsequent subtype assignment by the artificial neural network resulted in
      correct identification of 24 "unknown" A/H5N1 positive samples with no false
      positives. Analysis of a data set composed of A/H5N1, A/H3N2, and A/H1N1 positive
      samples and negative controls resulted in a clinical sensitivity of 97% and a
      clinical specificity of 100%.

PMID- 17194166
TI  - Statins and monitoring of liver function tests.

PMID- 17194167
TI  - Can we ensure the safe use of known human teratogens?: The iPLEDGE test case.
AB  - Minimising the public health burden of isotretinoin-induced teratogenicity has
      been a challenge for 24 years, the duration of availability of isotretinoin in
      the US for the treatment of severe, recalcitrant nodular acne. Although the
      teratogenicity of this drug is well known and risk-management programmes had been
      implemented, preventable fetal exposures continued to occur, largely as a result
      of the lack of sufficient controls within the programmes themselves. The
      manufacturers of isotretinoin implemented a new risk-management programme,
      iPLEDGE, in March 2006. iPLEDGE is a comprehensive distribution system that
      includes mandatory registration of patients, healthcare providers, pharmacies,
      and wholesalers. It allows real-time linkage of pregnancy-test results for
      verification prior to the dispensing of isotretinoin. Although the challenges of
      implementing a closed distribution system for a very widely used medication have
      been extensive, the potential public health benefits from preventing fetal
      exposure to isotretinoin are substantial.

PMID- 17194168
TI  - Treatment of attention deficit hyperactivity disorder in children and
      adolescents: safety considerations.
AB  - Despite a large body of evidence for both the validity of the diagnosis of
      attention deficit hyperactivity disorder (ADHD) and the efficacy of its treatment
      with medication, there is an equally long history of controversy. This article
      focuses on presenting safety information for medications approved by the US FDA
      for the treatment of individuals with ADHD. Stimulant medications are generally
      safe and effective. The common adverse effects of stimulant medications,
      including appetite suppression and insomnia, are usually of mild severity and
      manageable without stopping the medication. The more severe adverse effects such
      as tics or bizarre behaviours occur with low frequency and usually resolve when
      the medication is stopped. The possible impact on growth requires careful
      monitoring. Several rare but potentially severe adverse effects including sudden
      cardiac death and cancer following long-term treatment have been reported;
      however, these effects have not been adequately demonstrated to be of significant
      concern at this time. Atomoxetine also has a mild adverse effect profile in terms
      of severity and frequency although the numbers of studies and years of clinical
      experience is considerably less with this drug than for the stimulant
      medications. When the risks are juxtaposed to the clear efficacy in significantly
      reducing dysfunctional symptoms of ADHD, benefit-risk analyses support the
      continued use of these pharmacological treatments for patients with ADHD.

PMID- 17194170
TI  - Clozapine-associated myocarditis: a review of 116 cases of suspected myocarditis
      associated with the use of clozapine in Australia during 1993-2003.
AB  - BACKGROUND: Clozapine is an antipsychotic medication associated with a lower
      suicide rate compared with other antipsychotic agents. Clozapine is used
      specifically in patients for whom previous therapy was inadequate or not
      tolerated, and is the only antipsychotic agent associated with the development of
      myocarditis. OBJECTIVE: To retrospectively review all adverse drug reaction
      reports voluntarily submitted to the Australian Adverse Drug Reactions Unit
      mentioning suspected myocarditis in clozapine-treated patients. PATIENTS AND
      METHODS: We accessed all electronic database entries and case reports citing
      suspected myocarditis associated with clozapine therapy from January 1993 through
      to December 2003, inclusive. RESULTS: 116 case reports of suspected myocarditis
      amongst clozapine-treated patients were identified during the specified time
      frame (incidence between 0.7% and 1.2% of treated patients). Median patient age
      for these cases was 30 years (SD 11.1 years) compared with 37 years from the
      Clopine registry. The condition developed within a median 16 days (mean 19.8
      days; SD 17.3 days) of commencing clozapine for the bulk of patients developing
      myocarditis within 6 months (n=93, 80.2%). For all cases with known treatment
      commencement and cessation dates (n=106), the condition developed within a median
      17 days (mean 171.7 days, SD 530.9 days). Over nine-tenths of cases were
      prescribed clozapine within the dose range of 100 mg/day to 450 mg/day. Sixty
      patients (51.8%) recovered from their episode when reported or during follow-up
      reports, whereas 17 patients (14.7%) had not yet recovered: 27 patients (23.3%)
      had unknown outcome when reported and the remaining 12 patients (10.3%) died.
      CONCLUSION: Clozapine is uncommonly but importantly related to myocarditis, often
      fatal or near fatal and sometimes in relatively young patients with early onset
      after treatment initiation. The most striking feature about this condition is the
      wide diversity of nonspecific symptoms that occur in afflicted patients.
      Additional pharmacovigilance, improved reporting systems and further
      investigation of mechanisms of drug-induced myocarditis and related
      cardiovascular conditions (such as heart failure) are clearly warranted. A case
      control study would be suitable for investigation of baseline predictors.

PMID- 17194169
TI  - Drug-induced musculoskeletal disorders.
AB  - Drug-induced musculoskeletal disorders represent a broad clinical spectrum, from
      asymptomatic biological abnormalities to severe and even life-threatening
      diseases. Since an increasing number of drugs have been implicated in inducing
      rheumatic symptoms and/or syndromes, this review is not meant to be exhaustive,
      bearing in mind that the development of any musculoskeletal disorder should be
      considered as possibly related to a medication. The purpose of this article is to
      provide an overview of the more frequent drug-induced musculoskeletal disorders.
      These include: (i) arthralgias and arthropathies, including chondropathies and
      inflammatory arthritis; (ii) connective tissue diseases, especially lupus-like
      syndromes; (iii) periarticular disorders, including tendinopathies,
      enthesopathies and frozen shoulder; (iii) bone diseases, such as osteoporosis,
      osteomalacia and osteonecrosis; and (iv) myopathies. Although virtually all drug
      classes may induce musculoskeletal disorders, a significant part of them are
      related to corticosteroids, vaccines, antibacterials and lipid-lowering agents.
      Knowledge of drug-induced musculoskeletal disorders avoids carrying out
      unnecessary investigations, and allows optimal management of the patients, i.e.
      early discontinuation of the offending agent, adequate treatment monitoring
      and/or intervention with appropriate preventive actions.

PMID- 17194171
TI  - A population-based case-control teratologic study of oral dipyrone treatment
      during pregnancy.
AB  - OBJECTIVE: To study the possible human teratogenic effect of oral dipyrone, an
      antipyretic and analgesic drug treatment during pregnancy. DESIGN AND SETTING:
      The analysis of cases with different congenital abnormalities and their matched
      population controls without congenital abnormalities, in addition to a comparison
      between cases and malformation controls (Down's syndrome) in the population
      based, large data set of the Hungarian Case-Control Surveillance of Congenital
      Abnormalities, 1980-1996. STUDY PARTICIPANTS: 22 843 neonates or fetuses with
      congenital abnormalities (cases), 38 151 matched newborns without congenital
      abnormalities (population controls) and 834 neonates or fetuses with Down's
      syndrome (malformation controls). MAIN OUTCOME MEASURES: 25 congenital
      abnormality groups. RESULTS: 1382 (6%) cases, 1911 (5%) population controls and
      74 (8.9%) malformation controls were born to mothers treated with dipyrone during
      pregnancy. The case-matched population control analysis showed a higher rate of
      diaphragmatic defect (adjusted prevalence odds ratio [POR] 2.7; 95% CI 1.0, 6.8),
      cardiovascular malformations (POR 1.3; 95% CI 1.0, 1.7) and other isolated
      congenital abnormalities (POR 1.8; 95% CI 1.1, 2.9) after oral dipyrone treatment
      during the second and third months of gestation, i.e. in the critical period for
      most major congenital abnormalities. However, the evaluation of only medically
      recorded dipyrone use did not confirm these possible associations. The comparison
      of dipyrone treatment between 25 congenital abnormalities groups and malformation
      controls as the referent group also did not show any difference in the dipyrone
      use during the second and third months of gestation. CONCLUSIONS: The higher
      occurrence of dipyrone treatment in the case mothers compared with population
      control mothers can be explained by recall bias and/or chance. However, the
      higher rate of diaphragmatic congenital abnormalities can be considered as a
      signal and merits further investigation.

PMID- 17194172
TI  - Risk factors associated with a high velocity of the development of hyperkalaemia
      in hospitalised patients.
AB  - BACKGROUND/OBJECTIVE: Drugs have been recognised as a primary or contributing
      cause of hyperkalaemia, especially when administered to patients with underlying
      risk factors. The objective of this study was to analyse the influence of the
      known risk factors for hyperkalaemia on the velocity of the development of
      hyperkalaemia. STUDY DESIGN/METHODS: Clinical characteristics, laboratory data
      and medication profiles of patients developing hyperkalaemia (serum
      potassium>or=5.0 mmol/L) hospitalised between 2000 and 2004 in the University
      Hospital Basel, Switzerland, were recorded. Factors associated with a high
      velocity of the development of hyperkalaemia were detected using a multiple
      logistic regression model. Subsequently, the velocity during a defined
      observation period was compared between patients with one risk factor and
      patients with two or more risk factors. Finally, the dose effects of drugs
      identified as risk factors for a high velocity of the development of
      hyperkalaemia were analysed using two sample comparisons. RESULTS: A random
      sample of 551 hospitalised patients was analysed. Compared with the drug
      treatment at entry, significantly more patients during the hospitalisation were
      treated with drugs associated with hyperkalaemia, such as heparins (p<0.001), ACE
      inhibitors or angiotensin receptor blockers (ARBs) [p=0.002], potassium
      supplements (p<0.001), potassium-sparing diuretics (p<0.001) and/or NSAIDs or
      selective cyclo-oxygenase (COX)-2 inhibitors (p<0.001). Risk factors associated
      with a high velocity of the development of hyperkalaemia were use of potassium
      supplements (adjusted odds ratio [OR] 3.386; 95% CI 2.251, 5.091), severe renal
      impairment (OR 3.119; 95% CI 2.007, 4.850), use of ACE inhibitors or ARBs (OR
      2.642; 95% CI 1.742, 4.006), use of potassium-sparing diuretics (OR 2.065; 95% CI
      1.310, 3.254), and diabetes mellitus (OR 1.525; 95% CI 1.005, 2.313). The
      velocity of the development of hyperkalaemia significantly increased in patients
      with two or more risk factors. Dose effects could be found for potassium
      supplements (p=0.006) and potassium-sparing diuretics (p=0.007), but not for ACE
      inhibitors or ARBs (p=0.289). In contrast, the use of kaliuretics (loop diuretics
      or thiazides) was associated with a decreased velocity of the development of
      hyperkalaemia in patients with serious renal impairment (p=0.016) and in patients
      treated with two or more drug classes associated with a high velocity of the
      development of hyperkalaemia (p=0.001). CONCLUSIONS: Risk factors associated with
      a high velocity of the development of hyperkalaemia are use of potassium
      supplements>severe renal impairment>use of ACE inhibitors or ARBs>use of
      potassium-sparing diuretics>diabetes mellitus. The presence of two or more of
      these risk factors is associated with an even faster development of
      hyperkalaemia. Clinicians should be aware of these risk factors in order to avoid
      a rapid development of potentially life-threatening hyperkalaemia.

PMID- 17194174
TI  - Increase in nonfatal digestive perforations and haemorrhages following
      introduction of selective NSAIDs: a public health concern.

PMID- 17194180
TI  - Ophthalmoplegia and slurred speech in an intravenous drug user.

PMID- 17194173
TI  - Emergency department visits caused by adverse drug events: results of a French
      survey.
AB  - BACKGROUND: Adverse drug events (ADEs) are a substantial cause of hospital
      admissions. However, little is known about the incidence, preventability and
      severity of ADEs resulting in emergency department visits. To address this issue,
      we conducted a prospective survey in emergency departments of French public
      hospitals. METHODS: This study was performed over two periods of 1 week each, one
      in June 1999 and one in December 1999, in emergency departments of five
      university hospitals and five general hospitals throughout France. All patients
      aged>or=15 years presenting with medical complaints were included in the study.
      Trauma patients, those with gynaecological conditions and those with alcohol
      intoxication or intentional drug poisoning were excluded from the study. Each
      patient was assessed by two local emergency physicians to determine whether the
      visit was the result of an ADE. All medical records were subsequently validated
      by an independent group of medical lecturers in iatrogenic disorders. RESULTS:
      Out of a total of 1937 patients consulting, 1562 were taking at least one drug
      during the previous week and were included for analysis; 328 (21%; 95% CI 19, 23)
      of these patients consulted an emergency physician because of an ADE. Patients
      with ADEs were older than those without (mean age 63.5 vs 54.8 years; p<0.0001).
      Furthermore, ADE patients were more likely to have a higher severity presentation
      than the non-ADE group (p=0.019). The number of drug exposures was significantly
      higher in patients with an ADE than in those without (mean number of medications
      5.17 vs 3.82; p<0.0001). On multivariate analysis, only age and the number of
      medications taken were significantly associated with adverse events. In total,
      410 drugs were incriminated in the occurrence of 328 ADEs. The most frequently
      incriminated drug classes were: (i) psychotropic agents (n=84; 20.5%); (ii)
      diuretics (n=48; 11.7%), anticoagulants (n=38; 9.3%) and other cardiovascular
      drugs (n=63; 15.4%); and (iii) analgesics, including NSAIDs (n=57; 13.9%).
      Preventability could be assessed in 280 of the 328 cases. In 106 cases (37.9%),
      the ADE was judged to be preventable. CONCLUSION: ADEs leading to emergency
      department visits are frequent, and many are preventable, confirming that there
      is a need to develop prevention strategies.

PMID- 17194182
TI  - Healthy Penis: San Francisco's social marketing campaign to increase syphilis
      testing among gay and bisexual men.

PMID- 17194181
TI  - A gene expression signature predicts survival of patients with stage I non-small
      cell lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related death in the
      United States. Nearly 50% of patients with stages I and II non-small cell lung
      cancer (NSCLC) will die from recurrent disease despite surgical resection. No
      reliable clinical or molecular predictors are currently available for identifying
      those at high risk for developing recurrent disease. As a consequence, it is not
      possible to select those high-risk patients for more aggressive therapies and
      assign less aggressive treatments to patients at low risk for recurrence. METHODS
      AND FINDINGS: In this study, we applied a meta-analysis of datasets from seven
      different microarray studies on NSCLC for differentially expressed genes related
      to survival time (under 2 y and over 5 y). A consensus set of 4,905 genes from
      these studies was selected, and systematic bias adjustment in the datasets was
      performed by distance-weighted discrimination (DWD). We identified a gene
      expression signature consisting of 64 genes that is highly predictive of which
      stage I lung cancer patients may benefit from more aggressive therapy. Kaplan
      Meier analysis of the overall survival of stage I NSCLC patients with the 64-gene
      expression signature demonstrated that the high- and low-risk groups are
      significantly different in their overall survival. Of the 64 genes, 11 are
      related to cancer metastasis (APC, CDH8, IL8RB, LY6D, PCDHGA12, DSP, NID, ENPP2,
      CCR2, CASP8, and CASP10) and eight are involved in apoptosis (CASP8, CASP10,
      PIK3R1, BCL2, SON, INHA, PSEN1, and BIK). CONCLUSIONS: Our results indicate that
      gene expression signatures from several datasets can be reconciled. The resulting
      signature is useful in predicting survival of stage I NSCLC and might be useful
      in informing treatment decisions.

PMID- 17194183
TI  - Hypogammaglobulinemia with facial edema.

PMID- 17194184
TI  - Mining methylation for early detection of common cancers.

PMID- 17194185
TI  - TV and inactivity are separate contributors to metabolic risk factors in
      children.

PMID- 17194186
TI  - Stem cells and metastatic cancer: fatal attraction?

PMID- 17194187
TI  - A genome-wide screen for promoter methylation in lung cancer identifies novel
      methylation markers for multiple malignancies.
AB  - BACKGROUND: Promoter hypermethylation coupled with loss of heterozygosity at the
      same locus results in loss of gene function in many tumor cells. The "rules"
      governing which genes are methylated during the pathogenesis of individual
      cancers, how specific methylation profiles are initially established, or what
      determines tumor type-specific methylation are unknown. However, DNA methylation
      markers that are highly specific and sensitive for common tumors would be useful
      for the early detection of cancer, and those required for the malignant phenotype
      would identify pathways important as therapeutic targets. METHODS AND FINDINGS:
      In an effort to identify new cancer-specific methylation markers, we employed a
      high-throughput global expression profiling approach in lung cancer cells. We
      identified 132 genes that have 5' CpG islands, are induced from undetectable
      levels by 5-aza-2'-deoxycytidine in multiple non-small cell lung cancer cell
      lines, and are expressed in immortalized human bronchial epithelial cells. As
      expected, these genes were also expressed in normal lung, but often not in
      companion primary lung cancers. Methylation analysis of a subset (45/132) of
      these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant
      tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but
      did not show methylation in normal lung or peripheral blood cells. We studied the
      eight most frequently and specifically methylated genes from our lung cancer
      dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n
      = 24) along with counterpart nonmalignant tissues. We found that seven loci were
      frequently methylated in both breast and lung cancers, with four showing
      extensive methylation in all four epithelial tumors. CONCLUSIONS: By using a
      systematic biological screen we identified multiple genes that are methylated
      with high penetrance in primary lung, breast, colon, and prostate cancers. The
      cross-tumor methylation pattern we observed for these novel markers suggests that
      we have identified a partial promoter hypermethylation signature for these common
      malignancies. These data suggest that while tumors in different tissues vary
      substantially with respect to gene expression, there may be commonalities in
      their promoter methylation profiles that represent targets for early detection
      screening or therapeutic intervention.

PMID- 17194189
TI  - TV viewing and physical activity are independently associated with metabolic risk
      in children: the European Youth Heart Study.
AB  - BACKGROUND: TV viewing has been linked to metabolic-risk factors in youth.
      However, it is unclear whether this association is independent of physical
      activity (PA) and obesity. METHODS AND FINDINGS: We did a population-based, cross
      sectional study in 9- to 10-y-old and 15- to 16-y-old boys and girls from three
      regions in Europe (n = 1,921). We examined the independent associations between
      TV viewing, PA measured by accelerometry, and metabolic-risk factors (body
      fatness, blood pressure, fasting triglycerides, inverted high-density lipoprotein
      (HDL) cholesterol, glucose, and insulin levels). Clustered metabolic risk was
      expressed as a continuously distributed score calculated as the average of the
      standardized values of the six subcomponents. There was a positive association
      between TV viewing and adiposity (p = 0.021). However, after adjustment for PA,
      gender, age group, study location, sexual maturity, smoking status, birth weight,
      and parental socio-economic status, the association of TV viewing with clustered
      metabolic risk was no longer significant (p = 0.053). PA was independently and
      inversely associated with systolic and diastolic blood pressure, fasting glucose,
      insulin (all p < 0.01), and triglycerides (p = 0.02). PA was also significantly
      and inversely associated with the clustered risk score (p < 0.0001),
      independently of obesity and other confounding factors. CONCLUSIONS: TV viewing
      and PA may be separate entities and differently associated with adiposity and
      metabolic risk. The association between TV viewing and clustered metabolic risk
      is mediated by adiposity, whereas PA is associated with individual and clustered
      metabolic-risk indicators independently of obesity. Thus, preventive action
      against metabolic risk in children may need to target TV viewing and PA
      separately.

PMID- 17194188
TI  - Impact of extended-duration shifts on medical errors, adverse events, and
      attentional failures.
AB  - BACKGROUND: A recent randomized controlled trial in critical-care units revealed
      that the elimination of extended-duration work shifts (> or =24 h) reduces the
      rates of significant medical errors and polysomnographically recorded attentional
      failures. This raised the concern that the extended-duration shifts commonly
      worked by interns may contribute to the risk of medical errors being made, and
      perhaps to the risk of adverse events more generally. Our current study assessed
      whether extended-duration shifts worked by interns are associated with
      significant medical errors, adverse events, and attentional failures in a diverse
      population of interns across the United States. METHODS AND FINDINGS: We
      conducted a Web-based survey, across the United States, in which 2,737 residents
      in their first postgraduate year (interns) completed 17,003 monthly reports. The
      association between the number of extended-duration shifts worked in the month
      and the reporting of significant medical errors, preventable adverse events, and
      attentional failures was assessed using a case-crossover analysis in which each
      intern acted as his/her own control. Compared to months in which no extended
      duration shifts were worked, during months in which between one and four extended
      duration shifts and five or more extended-duration shifts were worked, the odds
      ratios of reporting at least one fatigue-related significant medical error were
      3.5 (95% confidence interval [CI], 3.3-3.7) and 7.5 (95% CI, 7.2-7.8),
      respectively. The respective odds ratios for fatigue-related preventable adverse
      events, 8.7 (95% CI, 3.4-22) and 7.0 (95% CI, 4.3-11), were also increased.
      Interns working five or more extended-duration shifts per month reported more
      attentional failures during lectures, rounds, and clinical activities, including
      surgery and reported 300% more fatigue-related preventable adverse events
      resulting in a fatality. CONCLUSIONS: In our survey, extended-duration work
      shifts were associated with an increased risk of significant medical errors,
      adverse events, and attentional failures in interns across the United States.
      These results have important public policy implications for postgraduate medical
      education.

PMID- 17194190
TI  - Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C
      virus in HIV coinfection.
AB  - BACKGROUND: Hepatitis C virus (HCV)-specific T cell responses are critical for
      spontaneous resolution of HCV viremia. Here we examined the effect of a
      lymphotropic virus, HIV-1, on the ability of coinfected patients to maintain
      spontaneous control of HCV infection. METHODS AND FINDINGS: We measured T cell
      responsiveness by lymphoproliferation and interferon-gamma ELISPOT in a large
      cohort of HCV-infected individuals with and without HIV infection. Among 47
      HCV/HIV-1-coinfected individuals, spontaneous control of HCV was associated with
      more frequent HCV-specific lymphoproliferative (LP) responses (35%) compared to
      coinfected persons who exhibited chronic HCV viremia (7%, p = 0.016), but less
      frequent compared to HCV controllers who were not HIV infected (86%, p = 0.003).
      Preservation of HCV-specific LP responses in coinfected individuals was
      associated with a higher nadir CD4 count (r(2) = 0.45, p < 0.001) and the
      presence and magnitude of the HCV-specific CD8(+) T cell interferon-gamma
      response (p = 0.0014). During long-term follow-up, recurrence of HCV viremia
      occurred in six of 25 coinfected individuals with prior control of HCV, but in 0
      of 16 HIV-1-negative HCV controllers (p = 0.03, log rank test). In these six
      individuals with recurrent HCV viremia, the magnitude of HCV viremia following
      recurrence inversely correlated with the CD4 count at time of breakthrough (r = 
      0.94, p = 0.017). CONCLUSIONS: These results indicate that HIV infection impairs
      the immune response to HCV-including in persons who have cleared HCV infection
      and that HIV-1-infected individuals with spontaneous control of HCV remain at
      significant risk for a second episode of HCV viremia. These findings highlight
      the need for repeat viral RNA testing of apparent controllers of HCV infection in
      the setting of HIV-1 coinfection and provide a possible explanation for the
      higher rate of HCV persistence observed in this population.

PMID- 17194192
TI  - Lipoprotein particle profiles mark familial and sporadic human longevity.
AB  - BACKGROUND: Genetic and biochemical studies have indicated an important role for
      lipid metabolism in human longevity. Ashkenazi Jewish centenarians and their
      offspring have large low-density lipoprotein (LDL) and high-density lipoprotein
      (HDL) particles as compared with control individuals. This profile also coincided
      with a lower prevalence of disease. Here, we investigate whether this observation
      can be confirmed for familial longevity in an outbred European population and
      whether it can be extended to sporadic longevity in the general population.
      METHODS AND FINDINGS: NMR-measured lipoprotein profiles were analyzed in 165
      families from the Leiden Longevity Study, consisting of 340 long-lived siblings
      (females >91 y, males >89 y), 511 of their offspring, and 243 partners of the
      offspring. Offspring had larger (21.3 versus 21.1 nm; p = 0.020) and fewer (1,470
      versus 1,561 nmol/l; p = 0.011) LDL particles than their same-aged partners. This
      effect was even more prominent in the long-lived siblings (p < 10(-3)) and could
      be pinpointed to a reduction specifically in the concentration of small LDL
      particles. No differences were observed for HDL particle phenotypes. The mean LDL
      particle sizes in 259 90-y-old singletons from a population-based study were
      similar to those in the long-lived siblings and thus significantly larger than in
      partners of the offspring, suggesting that the relevance of this phenotype
      extends beyond familial longevity. A low concentration of small LDL particles was
      associated with better overall health among both long-lived siblings (p = 0.003)
      and 90-y-old singletons (p = 0.007). CONCLUSIONS: Our study indicates that LDL
      particle profiles mark both familial and sporadic human longevity already in
      middle age.

PMID- 17194191
TI  - Tuberculosis among health-care workers in low- and middle-income countries: a
      systematic review.
AB  - BACKGROUND: The risk of transmission of Mycobacterium tuberculosis from patients
      to health-care workers (HCWs) is a neglected problem in many low- and middle
      income countries (LMICs). Most health-care facilities in these countries lack
      resources to prevent nosocomial transmission of tuberculosis (TB). METHODS AND
      FINDINGS: We conducted a systematic review to summarize the evidence on the
      incidence and prevalence of latent TB infection (LTBI) and disease among HCWs in
      LMICs, and to evaluate the impact of various preventive strategies that have been
      attempted. To identify relevant studies, we searched electronic databases and
      journals, and contacted experts in the field. We identified 42 articles,
      consisting of 51 studies, and extracted data on incidence, prevalence, and risk
      factors for LTBI and disease among HCWs. The prevalence of LTBI among HCWs was,
      on average, 54% (range 33% to 79%). Estimates of the annual risk of LTBI ranged
      from 0.5% to 14.3%, and the annual incidence of TB disease in HCWs ranged from 69
      to 5,780 per 100,000. The attributable risk for TB disease in HCWs, compared to
      the risk in the general population, ranged from 25 to 5,361 per 100,000 per year.
      A higher risk of acquiring TB disease was associated with certain work locations
      (inpatient TB facility, laboratory, internal medicine, and emergency facilities)
      and occupational categories (radiology technicians, patient attendants, nurses,
      ward attendants, paramedics, and clinical officers). CONCLUSIONS: In summary, our
      review demonstrates that TB is a significant occupational problem among HCWs in
      LMICs. Available evidence reinforces the need to design and implement simple,
      effective, and affordable TB infection-control programs in health-care facilities
      in these countries.

PMID- 17194193
TI  - Are residents' extended shifts associated with adverse events?

PMID- 17194194
TI  - Children with severe malnutrition: can those at highest risk of death be
      identified with the WHO protocol?
AB  - BACKGROUND: With strict adherence to international recommended treatment
      guidelines, the case fatality for severe malnutrition ought to be less than 5%.
      In African hospitals, fatality rates of 20% are common and are often attributed
      to poor training and faulty case management. Improving outcome will depend upon
      the identification of those at greatest risk and targeting limited health
      resources. We retrospectively examined the major risk factors associated with
      early (<48 h) and late in-hospital death in children with severe malnutrition
      with the aim of identifying admission features that could distinguish a high-risk
      group in relation to the World Health Organization (WHO) guidelines. METHODS AND
      FINDINGS: Of 920 children in the study, 176 (19%) died, with 59 (33%) deaths
      occurring within 48 h of admission. Bacteraemia complicated 27% of all deaths:
      52% died before 48 h despite 85% in vitro antibiotic susceptibility of cultured
      organisms. The sensitivity, specificity, and likelihood ratio of the WHO
      recommended "danger signs" (lethargy, hypothermia, or hypoglycaemia) to predict
      early mortality was 52%, 84%, and 3.4% (95% confidence interval [CI] = 2.2 to
      5.1), respectively. In addition, four bedside features were associated with early
      case fatality: bradycardia, capillary refill time greater than 2 s, weak pulse
      volume, and impaired consciousness level; the presence of two or more features
      was associated with an odds ratio of 9.6 (95% CI = 4.8 to 19) for early fatality
      (p < 0.0001). Conversely, the group of children without any of these seven
      features, or signs of dehydration, severe acidosis, or electrolyte derangements,
      had a low fatality (7%). CONCLUSIONS: Formal assessment of these features as
      emergency signs to improve triage and to rationalize manpower resources toward
      the high-risk groups is required. In addition, basic clinical research is
      necessary to identify and test appropriate supportive treatments.

PMID- 17194195
TI  - A plant-derived morphinan as a novel lead compound active against malaria liver
      stages.
AB  - BACKGROUND: The global spread of multidrug-resistant malaria parasites has led to
      an urgent need for new chemotherapeutic agents. Drug discovery is primarily
      directed to the asexual blood stages, and few drugs that are effective against
      the obligatory liver stages, from which the pathogenic blood infection is
      initiated, have become available since primaquine was deployed in the 1950s.
      METHODS AND FINDINGS: Using bioassay-guided fractionation based on the parasite's
      hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a
      plant traditionally used against malaria in Madagascar. This compound and readily
      obtained semisynthetic derivatives were tested for inhibitory activity against
      liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P.
      yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory
      concentration [IC50] 3.1 muM, therapeutic index [TI] 14) and P. falciparum (IC50
      4.2 muM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition
      being most pronounced during the early developmental stages. One derivative, N
      cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was
      selected for its lower toxicity (IC50 3.3 muM, TI 46, and IC50 42.4 muM, TI 60,
      on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral
      administration of NCP-tazopsine completely protected mice from a sporozoite
      challenge. Unlike the parent molecule, the derivative was uniquely active against
      Plasmodium hepatic stages. CONCLUSIONS: A readily obtained semisynthetic
      derivative of a plant-derived compound, tazopsine, has been shown to be
      specifically active against the liver stage, but inactive against the blood forms
      of the malaria parasite. This unique specificity in an antimalarial drug severely
      restricts the pressure for the selection of drug resistance to a parasite stage
      limited both in numbers and duration, thus allowing researchers to envisage the
      incorporation of a true causal prophylactic in malaria control programs.

PMID- 17194197
TI  - Cost-effectiveness of male circumcision for HIV prevention in a South African
      setting.
AB  - BACKGROUND: Consistent with observational studies, a randomized controlled
      intervention trial of adult male circumcision (MC) conducted in the general
      population in Orange Farm (OF) (Gauteng Province, South Africa) demonstrated a
      protective effect against HIV acquisition of 60%. The objective of this study is
      to present the first cost-effectiveness analysis of the use of MC as an
      intervention to reduce the spread of HIV in sub-Saharan Africa. METHODS AND
      FINDINGS: Cost-effectiveness was modeled for 1,000 MCs done within a general
      adult male population. Intervention costs included performing MC and treatment of
      adverse events. HIV prevalence was estimated from published estimates and
      incidence among susceptible subjects calculated assuming a steady-state epidemic.
      Effectiveness was defined as the number of HIV infections averted (HIA), which
      was estimated by dynamically projecting over 20 years the reduction in HIV
      incidence observed in the OF trial, including secondary transmission to women.
      Net savings were calculated with adjustment for the averted lifetime duration
      cost of HIV treatment. Sensitivity analyses examined the effects of input
      uncertainty and program coverage. All results were discounted to the present at
      3% per year. For Gauteng Province, assuming full coverage of the MC intervention,
      with a 2005 adult male prevalence of 25.6%, 1,000 circumcisions would avert an
      estimated 308 (80% CI 189-428) infections over 20 years. The cost is 181 dollars
      (80% CI 117-306 dollars) per HIA, and net savings are 2.4 million dollars (80% CI
      1.3 million to 3.6 million dollars). Cost-effectiveness is sensitive to the costs
      of MC and of averted HIV treatment, the protective effect of MC, and HIV
      prevalence. With an HIV prevalence of 8.4%, the cost per HIA is 551 dollars (80%
      CI 344-1,071 dollars) and net savings are 753,000 (80% CI 0.3 million to 1.2
      million dollars). Cost-effectiveness improves by less than 10% when MC
      intervention coverage is 50% of full coverage. CONCLUSIONS: In settings in sub
      Saharan Africa with high or moderate HIV prevalence among the general population,
      adult MC is likely to be a cost-effective HIV prevention strategy, even when it
      has a low coverage. MC generates large net savings after adjustment for averted
      HIV medical costs.

PMID- 17194196
TI  - Palladin mutation causes familial pancreatic cancer and suggests a new cancer
      mechanism.
AB  - BACKGROUND: Pancreatic cancer is a deadly disease. Discovery of the mutated genes
      that cause the inherited form(s) of the disease may shed light on the
      mechanism(s) of oncogenesis. Previously we isolated a susceptibility locus for
      familial pancreatic cancer to chromosome location 4q32-34. In this study, our
      goal was to discover the identity of the familial pancreatic cancer gene on 4q32
      and determine the function of that gene. METHODS AND FINDINGS: A customized
      microarray of the candidate chromosomal region affecting pancreatic cancer
      susceptibility revealed the greatest expression change in palladin (PALLD), a
      gene that encodes a component of the cytoskeleton that controls cell shape and
      motility. A mutation causing a proline (hydrophobic) to serine (hydrophilic)
      amino acid change (P239S) in a highly conserved region tracked with all affected
      family members and was absent in the non-affected members. The mutational change
      is not a known single nucleotide polymorphism. Palladin RNA, measured by
      quantitative RT-PCR, was overexpressed in the tissues from precancerous dysplasia
      and pancreatic adenocarcinoma in both familial and sporadic disease. Transfection
      of wild-type and P239S mutant palladin gene constructs into HeLa cells revealed a
      clear phenotypic effect: cells expressing P239S palladin exhibited cytoskeletal
      changes, abnormal actin bundle assembly, and an increased ability to migrate.
      CONCLUSIONS: These observations suggest that the presence of an abnormal palladin
      gene in familial pancreatic cancer and the overexpression of palladin protein in
      sporadic pancreatic cancer cause cytoskeletal changes in pancreatic cancer and
      may be responsible for or contribute to the tumor's strong invasive and migratory
      abilities.

PMID- 17194198
TI  - Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of
      small-study bias.
AB  - BACKGROUND: Inappropriate activation of the renin-angiotensin system may play a
      part in the development of preeclampsia. An insertion/deletion polymorphism
      within the angiotensin-I converting enzyme gene (ACE-I/D) has shown to be
      reliably associated with differences in angiotensin-converting enzyme (ACE)
      activity. However, previous studies of the ACE-I/D variant and preeclampsia have
      been individually underpowered to detect plausible genotypic risks. METHODS AND
      FINDINGS: A prospective case-control study was conducted in 1,711 unrelated young
      pregnant women (665 preeclamptic and 1,046 healthy pregnant controls) recruited
      from five Colombian cities. Maternal blood was obtained to genotype for the ACE
      I/D polymorphism. Crude and adjusted odds ratio (OR) and 95% confidence interval
      (CI) using logistic regression models were obtained to evaluate the strength of
      the association between ACE-I/D variant and preeclampsia risk. A meta-analysis
      was then undertaken of all published studies to February 2006 evaluating the ACE
      I/D variant in preeclampsia. An additive model (per-D-allele) revealed a null
      association between the ACE-I/D variant and preeclampsia risk (crude OR = 0.95
      [95% CI, 0.81-1.10]) in the new case-control study. Similar results were obtained
      after adjusting for confounders (adjusted per-allele OR = 0.90 [95% CI, 0.77
      1.06]) and using other genetic models of inheritance. A meta-analysis (2,596
      cases and 3,828 controls from 22 studies) showed a per-allele OR of 1.26 (95% CI,
      1.07-1.49). An analysis stratified by study size showed an attenuated OR toward
      the null as study size increased. CONCLUSIONS: It is highly likely that the
      observed small nominal increase in risk of preeclampsia associated with the ACE D
      allele is due to small-study bias, similar to that observed in cardiovascular
      disease. Reliable assessment of the origins of preeclampsia using a genetic
      approach may require the establishment of a collaborating consortium to generate
      a dataset of adequate size.

PMID- 17194201
TI  - Do we need a world health insurance to realise the right to health?

PMID- 17194199
TI  - Vaccine efficacy in senescent mice challenged with recombinant SARS-CoV bearing
      epidemic and zoonotic spike variants.
AB  - BACKGROUND: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was
      identified as the etiological agent of severe acute respiratory syndrome, a
      disease characterized by severe pneumonia that sometimes results in death. SARS
      CoV is a zoonotic virus that crossed the species barrier, most likely originating
      from bats or from other species including civets, raccoon dogs, domestic cats,
      swine, and rodents. A SARS-CoV vaccine should confer long-term protection,
      especially in vulnerable senescent populations, against both the 2003 epidemic
      strains and zoonotic strains that may yet emerge from animal reservoirs. We
      report the comprehensive investigation of SARS vaccine efficacy in young and
      senescent mice following homologous and heterologous challenge. METHODS AND
      FINDINGS: Using Venezuelan equine encephalitis virus replicon particles (VRP)
      expressing the 2003 epidemic Urbani SARS-CoV strain spike (S) glycoprotein (VRP
      S) or the nucleocapsid (N) protein from the same strain (VRP-N), we demonstrate
      that VRP-S, but not VRP-N vaccines provide complete short- and long-term
      protection against homologous strain challenge in young and senescent mice. To
      test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic
      analyses, synthetic biology, and reverse genetics to construct a chimeric virus
      (icGDO3-S) encoding a synthetic S glycoprotein gene of the most genetically
      divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03
      S replicated efficiently in human airway epithelial cells and in the lungs of
      young and senescent mice, and was highly resistant to neutralization with
      antisera directed against the Urbani strain. Although VRP-S vaccines provided
      complete short-term protection against heterologous icGD03-S challenge in young
      mice, only limited protection was seen in vaccinated senescent animals. VRP-N
      vaccines not only failed to protect from homologous or heterologous challenge,
      but resulted in enhanced immunopathology with eosinophilic infiltrates within the
      lungs of SARS-CoV-challenged mice. VRP-N-induced pathology presented at day 4,
      peaked around day 7, and persisted through day 14, and was likely mediated by
      cellular immune responses. CONCLUSIONS: This study identifies gaps and challenges
      in vaccine design for controlling future SARS-CoV zoonosis, especially in
      vulnerable elderly populations. The availability of a SARS-CoV virus bearing
      heterologous S glycoproteins provides a robust challenge inoculum for evaluating
      vaccine efficacy against zoonotic strains, the most likely source of future
      outbreaks.

PMID- 17194200
TI  - Erythrocyte G protein as a novel target for malarial chemotherapy.
AB  - BACKGROUND: Malaria remains a serious health problem because resistance develops
      to all currently used drugs when their parasite targets mutate. Novel
      antimalarial drug targets are urgently needed to reduce global morbidity and
      mortality. Our prior results suggested that inhibiting erythrocyte Gs signaling
      blocked invasion by the human malaria parasite Plasmodium falciparum. METHODS AND
      FINDINGS: We investigated the erythrocyte guanine nucleotide regulatory protein
      Gs as a novel antimalarial target. Erythrocyte "ghosts" loaded with a Gs peptide
      designed to block Gs interaction with its receptors, were blocked in beta
      adrenergic agonist-induced signaling. This finding directly demonstrates that
      erythrocyte Gs is functional and that propranolol, an antagonist of G protein
      coupled beta-adrenergic receptors, dampens Gs activity in erythrocytes. We
      subsequently used the ghost system to directly link inhibition of host Gs to
      parasite entry. In addition, we discovered that ghosts loaded with the peptide
      were inhibited in intracellular parasite maturation. Propranolol also inhibited
      blood-stage parasite growth, as did other beta2-antagonists. beta-blocker growth
      inhibition appeared to be due to delay in the terminal schizont stage. When used
      in combination with existing antimalarials in cell culture, propranolol reduced
      the 50% and 90% inhibitory concentrations for existing drugs against P.
      falciparum by 5- to 10-fold and was also effective in reducing drug dose in
      animal models of infection. CONCLUSIONS: Together these data establish that, in
      addition to invasion, erythrocyte G protein signaling is needed for intracellular
      parasite proliferation and thus may present a novel antimalarial target. The
      results provide proof of the concept that erythrocyte Gs antagonism offers a
      novel strategy to fight infection and that it has potential to be used to develop
      combination therapies with existing antimalarials.

PMID- 17194202
TI  - Enrolling adolescents in research on HIV: young women must be included.

PMID- 17194203
TI  - HIV-1 viral load assays for resource-limited settings: clades matter.

PMID- 17194204
TI  - Multidrug-resistant TB in the Philippines: totem and taboo.

PMID- 17194205
TI  - HIV-1 subtype and reverse transcriptase genotype: role for geographical location
      and founder effects.

PMID- 17194206
TI  - Reassurance: medically unexplained physical symptoms.

PMID- 17194207
TI  - Cost-effective control of drug-resistant TB: listening to other voices.

PMID- 17194211
TI  - Biosynthesis of selenocysteine on its tRNA in eukaryotes.
AB  - Selenocysteine (Sec) is cotranslationally inserted into protein in response to
      UGA codons and is the 21st amino acid in the genetic code. However, the means by
      which Sec is synthesized in eukaryotes is not known. Herein, comparative genomics
      and experimental analyses revealed that the mammalian Sec synthase (SecS) is the
      previously identified pyridoxal phosphate-containing protein known as the soluble
      liver antigen. SecS required selenophosphate and O-phosphoseryl-tRNA([Ser]Sec) as
      substrates to generate selenocysteyl-tRNA([Ser]Sec). Moreover, it was found that
      Sec was synthesized on the tRNA scaffold from selenide, ATP, and serine using
      tRNA([Ser]Sec), seryl-tRNA synthetase, O-phosphoseryl-tRNA([Ser]Sec) kinase,
      selenophosphate synthetase, and SecS. By identifying the pathway of Sec
      biosynthesis in mammals, this study not only functionally characterized SecS but
      also assigned the function of the O-phosphoseryl-tRNA([Ser]Sec) kinase. In
      addition, we found that selenophosphate synthetase 2 could synthesize
      monoselenophosphate in vitro but selenophosphate synthetase 1 could not.
      Conservation of the overall pathway of Sec biosynthesis suggests that this
      pathway is also active in other eukaryotes and archaea that synthesize
      selenoproteins.

PMID- 17194212
TI  - Alternative 3' pre-mRNA processing in Saccharomyces cerevisiae is modulated by
      Nab4/Hrp1 in vivo.
AB  - The Saccharomyces cerevisiae RNA-binding protein Nab4/Hrp1 is a component of the
      cleavage factor complex required for 3' pre-mRNA processing. Although the precise
      role of Nab4/Hrp1 remains unclear, it has been implicated in correct positioning
      of the cleavage site in vitro. Here, we show that mutation or overexpression of
      NAB4/HRP1 alters polyA cleavage site selection in vivo. Using bioinformatic
      analysis, we identified four related motifs that are statistically enriched in
      Nab4-associated transcripts; each motif is similar to the known binding site for
      Nab4/Hrp1. Site-directed mutations in predicted Nab4/Hrp1 binding elements result
      in decreased use of adjacent cleavage sites. Additionally, we show that the nab4
      7 mutant displays a striking resistance to toxicity from excess copper. We
      identify a novel target of alternative 3' pre-mRNA processing, CTR2, and
      demonstrate that CTR2 is required for the copper resistance phenotype in the nab4
      7 strain. We propose that alternative 3' pre-mRNA processing is mediated by a
      Nab4-based mechanism and that these alternative processing events could help
      control gene expression as part of a physiological response in S. cerevisiae.

PMID- 17194213
TI  - Drug export pathway of multidrug exporter AcrB revealed by DARPin inhibitors.
AB  - The multidrug exporter AcrB is the inner membrane component of the AcrAB-TolC
      drug efflux system in Escherichia coli and is responsible for the resistance of
      this organism to a wide range of drugs. Here we describe the crystal structure of
      the trimeric AcrB in complex with a designed ankyrin-repeat protein (DARPin)
      inhibitor at 2.5-A resolution. The three subunits of AcrB are locked in different
      conformations revealing distinct channels in each subunit. There seems to be
      remote conformational coupling between the channel access, exit, and the putative
      proton-translocation site, explaining how the proton motive force is used for
      drug export. Thus our structure suggests a transport pathway not through the
      central pore but through the identified channels in the individual subunits,
      which greatly advances our understanding of the multidrug export mechanism.

PMID- 17194214
TI  - An HIV feedback resistor: auto-regulatory circuit deactivator and noise buffer.
AB  - Animal viruses (e.g., lentiviruses and herpesviruses) use transcriptional
      positive feedback (i.e., transactivation) to regulate their gene expression. But
      positive-feedback circuits are inherently unstable when turned off, which
      presents a particular dilemma for latent viruses that lack transcriptional
      repressor motifs. Here we show that a dissipative feedback resistor, composed of
      enzymatic interconversion of the transactivator, converts transactivation
      circuits into excitable systems that generate transient pulses of expression,
      which decay to zero. We use HIV-1 as a model system and analyze single-cell
      expression kinetics to explore whether the HIV-1 transactivator of transcription
      (Tat) uses a resistor to shut off transactivation. The Tat feedback circuit was
      found to lack bi-stability and Tat self-cooperativity but exhibited a pulse of
      activity upon transactivation, all in agreement with the feedback resistor model.
      Guided by a mathematical model, biochemical and genetic perturbation of the
      suspected Tat feedback resistor altered the circuit's stability and reduced
      susceptibility to molecular noise, in agreement with model predictions. We
      propose that the feedback resistor is a necessary, but possibly not sufficient,
      condition for turning off noisy transactivation circuits lacking a repressor
      motif (e.g., HIV-1 Tat). Feedback resistors may be a paradigm for examining other
      auto-regulatory circuits and may inform upon how viral latency is established,
      maintained, and broken.

PMID- 17194215
TI  - Rate of evolution in brain-expressed genes in humans and other primates.
AB  - Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since
      brains of higher primates have evolved rapidly, one might expect acceleration in
      DNA sequence evolution in their brain-expressed genes. In this study, we carried
      out full-length cDNA sequencing on the brain transcriptome of an Old World monkey
      (OWM) and then conducted three-way comparisons among (i) mouse, OWM, and human,
      and (ii) OWM, chimpanzee, and human. Although brain-expressed genes indeed appear
      to evolve more rapidly in species with more advanced brains (apes > OWM > mouse),
      a similar lineage effect is observable for most other genes. The broad inclusion
      of genes in the reference set to represent the genomic average is therefore
      critical to this type of analysis. Calibrated against the genomic average, the
      rate of evolution among brain-expressed genes is probably lower (or at most
      equal) in humans than in chimpanzee and OWM. Interestingly, the trend of slow
      evolution in coding sequence is no less pronounced among brain-specific genes,
      vis-a-vis brain-expressed genes in general. The human brain may thus differ from
      those of our close relatives in two opposite directions: (i) faster evolution in
      gene expression, and (ii) a likely slowdown in the evolution of protein
      sequences. Possible explanations and hypotheses are discussed.

PMID- 17194216
TI  - Connectivity in the yeast cell cycle transcription network: inferences from
      neural networks.
AB  - A current challenge is to develop computational approaches to infer gene network
      regulatory relationships based on multiple types of large-scale functional
      genomic data. We find that single-layer feed-forward artificial neural network
      (ANN) models can effectively discover gene network structure by integrating
      global in vivo protein:DNA interaction data (ChIP/Array) with genome-wide
      microarray RNA data. We test this on the yeast cell cycle transcription network,
      which is composed of several hundred genes with phase-specific RNA outputs. These
      ANNs were robust to noise in data and to a variety of perturbations. They
      reliably identified and ranked 10 of 12 known major cell cycle factors at the top
      of a set of 204, based on a sum-of-squared weights metric. Comparative analysis
      of motif occurrences among multiple yeast species independently confirmed
      relationships inferred from ANN weights analysis. ANN models can capitalize on
      properties of biological gene networks that other kinds of models do not. ANNs
      naturally take advantage of patterns of absence, as well as presence, of factor
      binding associated with specific expression output; they are easily subjected to
      in silico "mutation" to uncover biological redundancies; and they can use the
      full range of factor binding values. A prominent feature of cell cycle ANNs
      suggested an analogous property might exist in the biological network. This
      postulated that "network-local discrimination" occurs when regulatory connections
      (here between MBF and target genes) are explicitly disfavored in one network
      module (G2), relative to others and to the class of genes outside the mitotic
      network. If correct, this predicts that MBF motifs will be significantly depleted
      from the discriminated class and that the discrimination will persist through
      evolution. Analysis of distantly related Schizosaccharomyces pombe confirmed
      this, suggesting that network-local discrimination is real and complements well
      known enrichment of MBF sites in G1 class genes.

PMID- 17194217
TI  - DARPP-32 is a robust integrator of dopamine and glutamate signals.
AB  - Integration of neurotransmitter and neuromodulator signals in the striatum plays
      a central role in the functions and dysfunctions of the basal ganglia. DARPP-32
      is a key actor of this integration in the GABAergic medium-size spiny neurons, in
      particular in response to dopamine and glutamate. When phosphorylated by cAMP
      dependent protein kinase (PKA), DARPP-32 inhibits protein phosphatase-1 (PP1),
      whereas when phosphorylated by cyclin-dependent kinase 5 (CDK5) it inhibits PKA.
      DARPP-32 is also regulated by casein kinases and by several protein phosphatases.
      These complex and intricate regulations make simple predictions of DARPP-32
      dynamic behaviour virtually impossible. We used detailed quantitative modelling
      of the regulation of DARPP-32 phosphorylation to improve our understanding of its
      function. The models included all the combinations of the three best
      characterized phosphorylation sites of DARPP-32, their regulation by kinases and
      phosphatases, and the regulation of those enzymes by cAMP and Ca(2+) signals.
      Dynamic simulations allowed us to observe the temporal relationships between cAMP
      and Ca(2+) signals. We confirmed that the proposed regulation of protein
      phosphatase-2A (PP2A) by calcium can account for the observed decrease of
      Threonine 75 phosphorylation upon glutamate receptor activation. DARPP-32 is not
      simply a switch between PP1-inhibiting and PKA-inhibiting states. Sensitivity
      analysis showed that CDK5 activity is a major regulator of the response, as
      previously suggested. Conversely, the strength of the regulation of PP2A by PKA
      or by calcium had little effect on the PP1-inhibiting function of DARPP-32 in
      these conditions. The simulations showed that DARPP-32 is not only a robust
      signal integrator, but that its response also depends on the delay between cAMP
      and calcium signals affecting the response to the latter. This integration did
      not depend on the concentration of DARPP-32, while the absolute effect on PP1
      varied linearly. In silico mutants showed that Ser137 phosphorylation affects the
      influence of the delay between dopamine and glutamate, and that constitutive
      phosphorylation in Ser137 transforms DARPP-32 in a quasi-irreversible switch.
      This work is a first attempt to better understand the complex interactions
      between cAMP and Ca(2+) regulation of DARPP-32. Progressive inclusion of
      additional components should lead to a realistic model of signalling networks
      underlying the function of striatal neurons.

PMID- 17194218
TI  - Population structure and eigenanalysis.
AB  - Current methods for inferring population structure from genetic data do not
      provide formal significance tests for population differentiation. We discuss an
      approach to studying population structure (principal components analysis) that
      was first applied to genetic data by Cavalli-Sforza and colleagues. We place the
      method on a solid statistical footing, using results from modern statistics to
      develop formal significance tests. We also uncover a general "phase change"
      phenomenon about the ability to detect structure in genetic data, which emerges
      from the statistical theory we use, and has an important implication for the
      ability to discover structure in genetic data: for a fixed but large dataset
      size, divergence between two populations (as measured, for example, by a
      statistic like FST) below a threshold is essentially undetectable, but a little
      above threshold, detection will be easy. This means that we can predict the
      dataset size needed to detect structure.

PMID- 17194219
TI  - Type III effector diversification via both pathoadaptation and horizontal
      transfer in response to a coevolutionary arms race.
AB  - The concept of the coevolutionary arms race holds a central position in our
      understanding of pathogen-host interactions. Here we identify the molecular
      mechanisms and follow the stepwise progression of an arms race in a natural
      system. We show how the evolution and function of the HopZ family of type III
      secreted effector proteins carried by the plant pathogen Pseudomonas syringae are
      influenced by a coevolutionary arms race between pathogen and host. We surveyed
      96 isolates of P. syringae and identified three homologs (HopZ1, HopZ2, and
      HopZ3) distributed among approximately 45% of the strains. All alleles were
      sequenced and their expression was confirmed. Evolutionary analyses determined
      that the diverse HopZ1 homologs are ancestral to P. syringae, and have diverged
      via pathoadaptive mutational changes into three functional and two degenerate
      forms, while HopZ2 and HopZ3 have been brought into P. syringae via horizontal
      transfer from other ecologically similar bacteria. A PAML selection analysis
      revealed that the C terminus of HopZ1 is under strong positive selection. Despite
      the extensive genetic variation observed in this family, all three homologs have
      cysteine-protease activity, although their substrate specificity may vary. The
      introduction of the ancestral hopZ1 allele into strains harboring alternate
      alleles results in a resistance protein-mediated defense response in their
      respective hosts, which is not observed with the endogenous allele. These data
      indicate that the P. syringae HopZ family has undergone allelic diversification
      via both pathoadaptive mutational changes and horizontal transfer in response to
      selection imposed by the host defense system. This genetic diversity permits the
      pathogen to avoid host defenses while still maintaining a virulence-associated
      protease, thereby allowing it to thrive on its current host, while simultaneously
      impacting its host range.

PMID- 17194220
TI  - Secrets of soil survival revealed by the genome sequence of Arthrobacter
      aurescens TC1.
AB  - Arthrobacter sp. strains are among the most frequently isolated, indigenous,
      aerobic bacterial genera found in soils. Member of the genus are metabolically
      and ecologically diverse and have the ability to survive in environmentally harsh
      conditions for extended periods of time. The genome of Arthrobacter aurescens
      strain TC1, which was originally isolated from soil at an atrazine spill site, is
      composed of a single 4,597,686 basepair (bp) circular chromosome and two circular
      plasmids, pTC1 and pTC2, which are 408,237 bp and 300,725 bp, respectively. Over
      66% of the 4,702 open reading frames (ORFs) present in the TC1 genome could be
      assigned a putative function, and 13.2% (623 genes) appear to be unique to this
      bacterium, suggesting niche specialization. The genome of TC1 is most similar to
      that of Tropheryma, Leifsonia, Streptomyces, and Corynebacterium glutamicum, and
      analyses suggest that A. aurescens TC1 has expanded its metabolic abilities by
      relying on the duplication of catabolic genes and by funneling metabolic
      intermediates generated by plasmid-borne genes to chromosomally encoded pathways.
      The data presented here suggest that Arthrobacter's environmental prevalence may
      be due to its ability to survive under stressful conditions induced by
      starvation, ionizing radiation, oxygen radicals, and toxic chemicals.

PMID- 17194221
TI  - Low levels of genetic divergence across geographically and linguistically diverse
      populations from India.
AB  - Ongoing modernization in India has elevated the prevalence of many complex
      genetic diseases associated with a western lifestyle and diet to near-epidemic
      proportions. However, although India comprises more than one sixth of the world's
      human population, it has largely been omitted from genomic surveys that provide
      the backdrop for association studies of genetic disease. Here, by genotyping
      India-born individuals sampled in the United States, we carry out an extensive
      study of Indian genetic variation. We analyze 1,200 genome-wide polymorphisms in
      432 individuals from 15 Indian populations. We find that populations from India,
      and populations from South Asia more generally, constitute one of the major human
      subgroups with increased similarity of genetic ancestry. However, only a
      relatively small amount of genetic differentiation exists among the Indian
      populations. Although caution is warranted due to the fact that United States
      sampled Indian populations do not represent a random sample from India, these
      results suggest that the frequencies of many genetic variants are distinctive in
      India compared to other parts of the world and that the effects of population
      heterogeneity on the production of false positives in association studies may be
      smaller in Indians (and particularly in Indian-Americans) than might be expected
      for such a geographically and linguistically diverse subset of the human
      population.

PMID- 17194222
TI  - Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and
      skeletogenesis.
AB  - Bone morphogenetic protein (BMP) family members, including BMP2, BMP4, and BMP7,
      are expressed throughout limb development. BMPs have been implicated in early
      limb patterning as well as in the process of skeletogenesis. However, due to
      complications associated with early embryonic lethality, particularly for Bmp2
      and Bmp4, and with functional redundancy among BMP molecules, it has been
      difficult to decipher the specific roles of these BMP molecules during different
      stages of limb development. To circumvent these issues, we have constructed a
      series of mouse strains lacking one or more of these BMPs, using conditional
      alleles in the case of Bmp2 and Bmp4 to remove them specifically from the limb
      bud mesenchyme. Contrary to earlier suggestions, our results indicate that BMPs
      neither act as secondary signals downstream of Sonic Hedghog (SHH) in patterning
      the anteroposterior axis nor as signals from the interdigital mesenchyme in
      specifying digit identity. We do find that a threshold level of BMP signaling is
      required for the onset of chondrogenesis, and hence some chondrogenic
      condensations fail to form in limbs deficient in both BMP2 and BMP4. However, in
      the condensations that do form, subsequent chondrogenic differentiation proceeds
      normally even in the absence of BMP2 and BMP7 or BMP2 and BMP4. In contrast, we
      find that the loss of both BMP2 and BMP4 results in a severe impairment of
      osteogenesis.

PMID- 17194226
TI  - Stability of a practical measure of recovery from resistance training.
AB  - McLester et al. (2003) proposed a practical protocol to determine optimal
      recovery times between resistance training workouts. For this protocol to be
      useful, it must be stable. The purpose of this study was to investigate the
      stability of that protocol. College-aged resistance trained men (n = 10)
      performed 3 sets to volitional failure using a 10-repetition maximum load for 6
      exercises. Recovery was evaluated on 4 occasions by the number of repetitions
      performed for each individual exercise after recovery periods of 48, 72, 96, and
      120 hours in counterbalanced order. To evaluate stability, this procedure was
      performed twice. The number of repetitions after each recovery interval were
      compared with initial baseline performances. A priori, adequate stability was
      defined as 70% of the participants achieving similar recovery duration on both
      trials. Pooled repetitions over all 6 exercises indicated that 80% of
      participants returned to baseline strength levels after the same recovery
      duration for both trials. However, when individual muscle group repetition
      performance was evaluated, stability varied from 20 to 70%. Variability in rest,
      nutrition, prior activity, and other factors probably induced instability in
      individual strength measures, but not sufficiently to influence the aggregate
      results. Some muscle groups may have greater sensitivity to variations in
      ecological factors such as these. We believe that the tested protocol may be
      useful in establishing recovery times for multimuscle group workouts, but not
      stable enough to be useful in establishing recovery times for individual muscle
      groups.

PMID- 17194224
TI  - Tissue-specific differences in human transfer RNA expression.
AB  - Over 450 transfer RNA (tRNA) genes have been annotated in the human genome.
      Reliable quantitation of tRNA levels in human samples using microarray methods
      presents a technical challenge. We have developed a microarray method to quantify
      tRNAs based on a fluorescent dye-labeling technique. The first-generation tRNA
      microarray consists of 42 probes for nuclear encoded tRNAs and 21 probes for
      mitochondrial encoded tRNAs. These probes cover tRNAs for all 20 amino acids and
      11 isoacceptor families. Using this array, we report that the amounts of tRNA
      within the total cellular RNA vary widely among eight different human tissues.
      The brain expresses higher overall levels of nuclear encoded tRNAs than every
      tissue examined but one and higher levels of mitochondrial encoded tRNAs than
      every tissue examined. We found tissue-specific differences in the expression of
      individual tRNA species, and tRNAs decoding amino acids with similar chemical
      properties exhibited coordinated expression in distinct tissue types. Relative
      tRNA abundance exhibits a statistically significant correlation to the codon
      usage of a collection of highly expressed, tissue-specific genes in a subset of
      tissues or tRNA isoacceptors. Our findings demonstrate the existence of tissue
      specific expression of tRNA species that strongly implicates a role for tRNA
      heterogeneity in regulating translation and possibly additional processes in
      vertebrate organisms.

PMID- 17194223
TI  - Evaluating support for the current classification of eukaryotic diversity.
AB  - Perspectives on the classification of eukaryotic diversity have changed rapidly
      in recent years, as the four eukaryotic groups within the five-kingdom
      classification--plants, animals, fungi, and protists--have been transformed
      through numerous permutations into the current system of six "supergroups." The
      intent of the supergroup classification system is to unite microbial and
      macroscopic eukaryotes based on phylogenetic inference. This supergroup approach
      is increasing in popularity in the literature and is appearing in introductory
      biology textbooks. We evaluate the stability and support for the current six
      supergroup classification of eukaryotes based on molecular genealogies. We assess
      three aspects of each supergroup: (1) the stability of its taxonomy, (2) the
      support for monophyly (single evolutionary origin) in molecular analyses
      targeting a supergroup, and (3) the support for monophyly when a supergroup is
      included as an out-group in phylogenetic studies targeting other taxa. Our
      analysis demonstrates that supergroup taxonomies are unstable and that support
      for groups varies tremendously, indicating that the current classification scheme
      of eukaryotes is likely premature. We highlight several trends contributing to
      the instability and discuss the requirements for establishing robust clades
      within the eukaryotic tree of life.

PMID- 17194228
TI  - Variations in heart rate at blood lactate threshold due to exercise mode in elite
      cross-country skiers.
AB  - This study attempted to quantify the difference in heart rate and exercise stage
      at which blood lactate threshold (T(bla)) occurs using 3 different modes of
      exercise: running, double poling (DP) on roller skis, and skating (SK) on roller
      skis. Nine elite collegiate cross-country ski racers (4 men, 5 women) served as
      test subjects. Testing was conducted on a motorized FitNex treadmill, specially
      designed for roller skiing. Heart rate was monitored via telemetry with values
      averaged over the last 30 seconds of each stage. A 40-micro l blood sample was
      obtained at the fingertip at the end of each 4-minute stage, and 25 micro l was
      analyzed for whole blood lactate concentration. The T(bla) was determined by the
      first exercise stage that elicited a concentration over 4.0 mmol.L(-1). The same
      test protocol was used for all 3 exercise modes. Mean heart rate, in beats per
      minute (b.min(-1)), at T(bla) was not significantly different (P < or = 0.05) for
      SK (mean 187 +/- 14 b.min(-1) SD) vs. running (mean 187 +/- 12 b.min(-1) SD);
      however, heart rate was significantly lower at T(bla) for DP (mean 161 +/- 17
      b.min(-1) SD) vs. running and DP vs. SK. The mean exercise protocol stage that
      induced a blood lactate value which exceeded T(bla) was significantly different
      (P < or = 0.05) for running (5.22 +/- 1.20 mmol.L(-1) SD) vs. DP (1.89 +/- 0.78
      mmol.L(-1) SD), running vs. SK (3.67 +/- 0.71 mmol.L(-1) SD), and SK vs. DP. It
      was concluded that T(bla) occurs at a lower heart rate and exercise stage during
      DP as compared with SK or running. Therefore, it stands to reason that the heart
      rate at T(bla) may vary based on mode of exercise, and when using heart rate to
      estimate blood lactate concentration, coaches and athletes should be aware that
      different modes of exercise elicit a different blood lactate concentration at a
      given heart rate depending on exercise mode used.

PMID- 17194227
TI  - The impact of velocity of movement on performance factors in resistance exercise.
AB  - The purpose of this study was to determine the impact of a very slow (VS)
      velocity and a self-selected volitional (VOL) velocity at varying intensities on
      repetition number, peak force, peak power, and total volume in the squat and
      shoulder press exercises. On separate testing days, 9 resistance trained men
      (age: 23.9 +/- 2.5 years; height: 174.8 +/- 6.5 cm; body mass: 80.1 +/- 12.4 kg)
      performed a squat (SQ) and shoulder press (SP) exercise at 60 or 80% of 1
      repetition maximum (1RM) at either VOL or VS (10-second eccentric and 10-second
      concentric actions) velocity for as many repetitions as possible. Force, power,
      and volume (repetitions x kg) were also determined. Subjects performed
      significantly fewer repetitions (p < or = 0.05) in the VS exercises (60% VS SQ 5
      +/- 1 vs. VOL SQ 24 +/- 2; 80% VS SQ 2 +/- 0 vs. VOL SQ 12 +/- 1; 60% VS SP 4 +/-
      1 vs. VOL SP 14 +/- 2; 80% VS SP 1 +/- 0 vs. VOL SP 6 +/- 1). Peak force and
      power were significantly higher at the VOL speed (peak force [in newtons]: 60% VS
      SQ 564.4 +/- 77.3 vs. VOL SQ 1229.0 +/- 134.9 N; 80% VS SQ 457.3 +/- 27.9 vs. VOL
      SQ 1059.3 +/- 104.7 N; 60% VS SP 321.6 +/- 37.8 vs. VOL SP 940.7 +/- 144.8 N; 80%
      VS SP 296.5 +/- 24.7 vs. VOL SP 702.5 +/- 57.7 N; and peak power [in watts]: 60%
      VS SQ 271.2 +/- 40.1 vs. VOL SQ 783.2 +/- 129.1 W; 80% VS SQ 229.3 +/- 49.5 vs.
      VOL SQ 520.2 +/- 85.8 W; 60% VS SP 91.3 +/- 21.9 vs. VOL SP 706.6 +/- 151.4 W;
      80% VS SP 78.1 +/- 19.8 vs. VOL SP 277.6 +/- 46.4 W). VOL speed elicited higher
      total volume than the VS velocity. The results of this study indicate that a VS
      velocity may not elicit appropriate levels of force, power, or volume to optimize
      strength and athletic performance.

PMID- 17194229
TI  - The effects of sprint running training on sloping surfaces.
AB  - The aim of this study was to examine the effects of sprint running training on
      sloping surfaces (3 degrees ) on selected kinematic and physiological variables.
      Thirty-five sport and physical education students were randomized into 4 training
      groups (uphill-downhill, downhill, uphill, and horizontal) and a control group,
      with 7 participants in each group. Pre- and posttraining tests were performed to
      examine the effects of 6 weeks of training on the maximum running speed at 35 m,
      step rate, step length, step time, contact time, eccentric and concentric phase
      of contact time, flight time, selected posture characteristics of the step cycle,
      and peak anaerobic power performance. Maximum running speed and step rate were
      increased significantly (p < 0.05) in a 35-m running test after training by 0.29
      m.s(-1) (3.5%) and 0.14 Hz (3.4%) for the combined uphill-downhill group and by
      0.09 m.s(-1) (1.1%) and 0.03 Hz (2.4%) for the downhill group, whereas flight
      time shortened only for the combined uphill-downhill training group by 6
      milliseconds (4.3%). There were no significant changes in the horizontal and
      control groups. Overall, the posture characteristics and the peak anaerobic power
      performance did not change with training. It can be suggested that the novel
      combined uphill-downhill training method is significantly more effective in
      improving the maximum running velocity at 35 m and the associated horizontal
      kinematic characteristics of sprint running than the other training methods are.

PMID- 17194230
TI  - A preliminary investigation of the biomechanical and perceptual influence of
      chain resistance on the performance of the snatch.
AB  - The purpose of this study was to determine whether the addition of chains to a
      barbell during the performance of the snatch would invoke differences in
      execution compared with lifting a conventional barbell without chains.
      Additionally, subjects were asked whether they perceived that the addition of
      chains had effects on their performance, and, if so, what those effects were.
      Four male and 3 female competitive weightlifters who regularly used chains as
      part of their training programs participated in the study. They were compared
      lifting 80% of 1 repetition maximum (1RM) using conventional barbells with 80% of
      1RM, 5% of which was accounted for by chains. The same procedure was used with
      85% of 1RM. Variables examined included maximum vertical displacement of the bar,
      maximum bar velocity, rate of force production of the bar, and vertical ground
      reaction forces for the first pull, unweighting, and second pull phases of the
      lift. Results indicated that there were no statistically significant differences
      between the chain vs. no-chain conditions at either 80% or 85% of 1RM. In
      contrast, 100% of the subjects stated that they perceived that the addition of
      chains made them work harder during the snatch. They suggested that the chains
      forced them to pull harder throughout the lift and that oscillation of the chains
      required their shoulders, abdominals, and back to work harder to stabilize the
      bar in the catch phase. Although statistical results indicate that chains have no
      influence on the snatch technique, chains may have a psychological impact and
      possibly invoke a physiological training response by increasing strength of
      muscles required to stabilize the bar during the catch phase if used over time.

PMID- 17194231
TI  - Effects of resistance training on the physical capacities of adolescent soccer
      players.
AB  - This study examined the effects of a progressive resistance training program in
      addition to soccer training on the physical capacities of male adolescents.
      Eighteen soccer players (age: 12-15 years) were separated in a soccer (SOC; n =
      9) and a strength-soccer (STR; n = 9) training group and 8 subjects of similar
      age constituted a control group. All players followed a soccer training program 5
      times a week for the development of technical and tactical skills. In addition,
      the STR group followed a strength training program twice a week for 16 weeks. The
      program included 10 exercises, and at each exercise, 2-3 sets of 8-15 repetitions
      with a load 55-80% of 1 repetition maximum (1RM). Maximum strength ([1RM] leg
      press, bench-press), jumping ability (squat jump [SJ], countermovement jump
      [CMJ], repeated jumps for 30 seconds) running speed (30 m, 10 x 5-m shuttle run),
      flexibility (seat and reach), and soccer technique were measured at the
      beginning, after 8 weeks, and at the end of the training period. After 16 weeks
      of training, 1RM leg press, 10 x 5-m shuttle run speed, and performance in soccer
      technique were higher (p < 0.05) for the STR and the SOC groups than for the
      control group. One repetition maximum bench press and leg press, SJ and CMJ
      height, and 30-m speed were higher (p < 0.05) for the STR group compared with SOC
      and control groups. The above data show that soccer training alone improves more
      than normal growth maximum strength of the lower limps and agility. The addition
      of resistance training, however, improves more maximal strength of the upper and
      the lower body, vertical jump height, and 30-m speed. Thus, the combination of
      soccer and resistance training could be used for an overall development of the
      physical capacities of young boys.

PMID- 17194232
TI  - Influence of a twelve-month conditioning program on physical growth, serum
      hormones, and neuromuscular performance of peripubertal male fencers.
AB  - This study examined the effects of a typical fencing training program on selected
      hormones, neuromuscular performance, and anthropometric parameters in
      peripubertal boys. Two sets of measurements, before training and after 12 months
      of training, were performed on 2 groups of 11- to 13-year-old boys. One group
      consisted of fencers (n = 8), who trained regularly for the 12-month period, and
      the other group (n = 8) consisted of inactive children of the same age. There was
      no difference in Tanner's maturation stage of the 2 groups before (controls, 2.5
      +/- 0.3; fencers, 2.1 +/- 0.3) and after the 12 months (controls, 3.0 +/- 0.3;
      fencers, 3.0 +/- 0.3). Serum testosterone, growth hormone, sex hormone binding
      globulin, free androgen index, and leptin changed significantly over time,
      reaching similar values in the 2 groups at the end of the study. Significantly
      greater increases in body mass (16 +/- 3%) and leg cross-sectional area (CSA) (32
      +/- 7%) were observed only in the fencers' group, and these differences
      disappeared when height was set as a changing covariate. Although there was a
      greater increase in height for the fencers compared to the control group (8.6 +/-
      1.2 vs. 3.6 +/- 0.9 cm, p < 0.01), the height reached at the end of the study was
      almost identical in the 2 groups (controls, 163.6 +/- 5.1; fencers, 165.4 +/-
      2.8). Arm CSA, handgrip strength, and vertical jump performance changed
      significantly over time for both groups, with no differences between groups. It
      was concluded that a typical fencing training program for peripubertal boys did
      not have any effect on selected growth and anabolic hormones and did not
      influence the normal growth process, as this was reflected by changes in selected
      anthropometric and neuromuscular performance parameters. This may be because of
      the characteristics of the present fencing training program, which may not be
      adequate to alter children's hormonal functions in such a way as to override the
      rapid changes occurring during puberty.

PMID- 17194233
TI  - The effects of caffeine on athletic agility.
AB  - Caffeine has been shown to improve sprint time, anaerobic power, and reaction
      time, all integral aspects of agility. The purpose of this study was to determine
      whether an acute caffeine dose would enhance agility and anaerobic power. Sixteen
      subjects participated in a randomized, double-blind experiment and performed the
      proagility run and the 30-second Wingate test 60 minutes after ingestion of
      caffeine (6 mg.kg(-1)) or placebo. No significant change was observed in the
      proagility run after caffeine ingestion compared with placebo. Also, no
      significant change was observed in peak power, mean power, or percent power
      decrease. Agility is an integral component of athletic skill and any reasonable
      method for enhancing agility would benefit active individuals. However, results
      from this study indicate that a 6 mg.kg(-1) dose of caffeine does not impact
      agility as measured by the proagility run test or power output as measured by the
      30-second Wingate test in recreationally active young adult males who are not
      habituated to caffeine.

PMID- 17194234
TI  - Velocity specificity in early-phase sprint training.
AB  - A comparison of resistance running, normal sprint running, and supramaximal
      running was performed. Nineteen young, generally well-trained subjects were
      divided into 3 training groups: resistance, normal, and supramaximal groups.
      Resistance and supramaximal training was done using a towing device, providing
      extra resistance or propulsion forces, resulting in running speed differences of
      about 3.3% (supramaximal) and 8.5% (resistance), compared to normal sprinting.
      The training period was 6 weeks, with 3 training sessions per week (5 sprint-runs
      over 22 m). Running times were measured using photocells, and average step length
      and cadence were recorded by digital video. A small (0.5%) but significant (p <
      0.05) overall pre-post difference was found in running velocity, but the 3 groups
      changed differently over the running conditions. All individual subjects improved
      sprinting velocity most on the trained form, at 1-2% (p < 0.001), and thus, the
      principle of velocity specificity in sprint training was supported. This
      indicates that to obtain short-distance sprinting improvement in a short period
      of time, one may prefer normal sprinting over other training forms.

PMID- 17194235
TI  - Prediction of one-hour running performance using constant duration tests.
AB  - Critical velocity (CV) represents, theoretically, the highest velocity that can
      be sustained without fatigue. The aim of this study was to compare CV computed
      from 5 mathematical models in order to determine which CV estimate is better
      correlated with 1-hour performance and which model provides the most accurate
      prediction of performance. Twelve trained middle- and long-distance male runners
      (29 +/- 5 years) performed 3 randomly ordered constant duration tests (6, 9, and
      12 minutes), a maximal running velocity test for the estimation of CV, and a 1
      hour track test (actual performance). Two linear, 2 nonlinear, and 1 exponential
      mathematical models were used to estimate CV and to predict the highest velocity
      that could be sustained during 1 hour (predicted performance). Although all CV
      estimates were correlated with performance (0.80 < r < 0.93, p < 0.01), it
      appeared that CV estimated from the exponential model was more closely associated
      with performance than all other models (r = 0.93; p < 0.01). Analysis of the bias
      +/- 95% interval of confidence between actual and predicted performance revealed
      that none of the models provided an accurate prediction of the 1-hour performance
      velocity. In conclusion, the estimation of CV allows us to rank middle- and long
      distance runners with regard to their ability to perform well in long-distance
      running. However, no models provide an accurate prediction of performance that
      could be used as a reference for coaches or athletes.

PMID- 17194236
TI  - A brief review: factors affecting the length of the rest interval between
      resistance exercise sets.
AB  - Research has indicated that multiple sets are superior to single sets for maximal
      strength development. However, whether maximal strength gains are achieved may
      depend on the ability to sustain a consistent number of repetitions over
      consecutive sets. A key factor that determines the ability to sustain repetitions
      is the length of rest interval between sets. The length of the rest interval is
      commonly prescribed based on the training goal, but may vary based on several
      other factors. The purpose of this review was to discuss these factors in the
      context of different training goals. When training for muscular strength, the
      magnitude of the load lifted is a key determinant of the rest interval prescribed
      between sets. For loads less than 90% of 1 repetition maximum, 3-5 minutes rest
      between sets allows for greater strength increases through the maintenance of
      training intensity. However, when testing for maximal strength, 1-2 minutes rest
      between sets might be sufficient between repeated attempts. When training for
      muscular power, a minimum of 3 minutes rest should be prescribed between sets of
      repeated maximal effort movements (e.g., plyometric jumps). When training for
      muscular hypertrophy, consecutive sets should be performed prior to when full
      recovery has taken place. Shorter rest intervals of 30-60 seconds between sets
      have been associated with higher acute increases in growth hormone, which may
      contribute to the hypertrophic effect. When training for muscular endurance, an
      ideal strategy might be to perform resistance exercises in a circuit, with
      shorter rest intervals (e.g., 30 seconds) between exercises that involve
      dissimilar muscle groups, and longer rest intervals (e.g., 3 minutes) between
      exercises that involve similar muscle groups. In summary, the length of the rest
      interval between sets is only 1 component of a resistance exercise program
      directed toward different training goals. Prescribing the appropriate rest
      interval does not ensure a desired outcome if other components such as intensity
      and volume are not prescribed appropriately.

PMID- 17194237
TI  - Isokinetic strength of collegiate baseball pitchers during a season.
AB  - Pitching is suggested to expose the arm to physical stress that may lead to a
      decrease in strength. The purpose of this study was to examine the isokinetic
      internal and external rotational shoulder strength of Division II pitchers
      preseason, midseason, and postseason. The 9 pitchers were 23 +/- 0.67 years of
      age and weighed 91.2 +/- 3.14 kg. Each subject was evaluated utilizing a Biodex
      Isokinetic Dynamometer. Isokinetic internal and external concentric strength was
      assessed at 90 degrees of shoulder abduction and 90 degrees of elbow flexion at
      300 and 450 degrees .s(-1) at each time point. A repeated-measures analysis of
      variance statistical analysis was performed using SPSS software. All data are
      reported as mean +/- SEM. Mean internal peak torques at 300 and 450 degrees .s(
      1) preseason, midseason, and postseason were 50.66 +/- 2.27, 49.70 +/- 2.54, and
      51.70 +/- 2.94 N.m and 37.14 +/- 2.54, 37.36 +/- 2.74, and 38.26 +/- 2.50 N.m,
      respectively. Mean external peak torques at 300 and 450 degrees .s(-1) preseason,
      midseason, and postseason were 30.16 +/- 1.69, 29.50 +/- 2.22, and 29.79 +/- 2.08
      N.m and 17.68 +/- 2.15, 16.89 +/- 2.46, and 18.20 +/- 2.35 N.m, respectively.
      There were no differences in isokinetic internal or external concentric shoulder
      rotational mean peak torque of Division II pitchers at any speed tested or time
      point examined.

PMID- 17194238
TI  - Increased deltoid and abdominal muscle activity during Swiss ball bench press.
AB  - The swiss is widely used in the recreational training environment as a supplement
      to conventional resistance training. One such application is to use the swiss
      ball as a bench support for bench press exercise. There is no evidence to
      indicate that the use of a swiss ball is beneficial for resistance training
      exercise. This study investigated muscle activity using surface electromyography
      of upper-body and abdominal muscles during the concentric and eccentric phases of
      the bench press on and off a swiss ball. Volunteers for this study were 14
      resistance-trained subjects who performed isolated concentric and eccentric bench
      press repetitions using the 2 test surfaces with a 2-second cadence at a load
      equivalent to 60% maximum force output. The average root mean square of the
      muscle activity was calculated for each movement, and perceived exertion during
      the tasks was collected using a Borg Scale. The results of the study showed that
      deltoid and abdominal muscle activity was increased for repetitions performed
      using the swiss ball. Increased deltoid muscle activity supports previous
      findings for increased activity when greater instability is introduced to the
      bench press movement. Abdominal muscle activity increases were not hypothesized,
      but this finding provides scientific evidence for anecdotal reasoning behind
      swiss ball use as a potential core stability training device.

PMID- 17194239
TI  - Relationship between the number of repetitions and selected percentages of one
      repetition maximum in free weight exercises in trained and untrained men.
AB  - Resistance exercise intensity is commonly prescribed as a percent of 1 repetition
      maximum (1RM). However, the relationship between percent 1RM and the number of
      repetitions allowed remains poorly studied, especially using free weight
      exercises. The purpose of this study was to determine the maximal number of
      repetitions that trained (T) and untrained (UT) men can perform during free
      weight exercises at various percentages of 1RM. Eight T and 8 UT men were tested
      for 1RM strength. Then, subjects performed 1 set to failure at 60, 80, and 90% of
      1RM in the back squat, bench press, and arm curl in a randomized, balanced
      design. There was a significant (p < 0.05) intensity x exercise interaction. More
      repetitions were performed during the back squat than the bench press or arm curl
      at 60% 1RM for T and UT. At 80 and 90% 1RM, there were significant differences
      between the back squat and other exercises; however, differences were much less
      pronounced. No differences in number of repetitions performed at a given exercise
      intensity were noted between T and UT (except during bench press at 90% 1RM). In
      conclusion, the number of repetitions performed at a given percent of 1RM is
      influenced by the amount of muscle mass used during the exercise, as more
      repetitions can be performed during the back squat than either the bench press or
      arm curl. Training status of the individual has a minimal impact on the number of
      repetitions performed at relative exercise intensity.

PMID- 17194240
TI  - The validation of a portable force plate for measuring force-time data during
      jumping and landing tasks.
AB  - The purpose of this study was to determine the reliability and validity of a
      portable force plate when analyzing jumping and landing tasks. Subjects performed
      3 drop vertical jumps and 3 drop landings on both a standard strain gauge
      laboratory force plate and a portable force plate. In contrast to typical
      laboratory installed force plates, the portable 6-component force plate can be
      easily transported and used onsite at various training or data collection sites
      and incorporates Hall effect technology. The measured parameters included maximum
      force and time to maximum force for initial stance of the both tests, maximum
      takeoff force, and time to maximum takeoff force for the drop vertical jump. The
      Pearson correlation coefficients for the drop landing and the drop vertical jump
      for maximum force (r = 0.942, r = 0.940), time to maximum force (r = 0.891, r =
      0.920) and for drop jump maximum jumping force (r = 0.971), and time to maximum
      takeoff force (r = 0.917) were all high and indicate that the force data
      collected by a resistor-type portable force plate provide similar measures to a
      standard strain-gauge laboratory force plate. Additionally, the within session
      reliability of the drop landing and the drop vertical jump measured by the
      portable force plate showed high interclass correlation coefficients for examined
      variables of 0.979 and 9.67 for maximum landing force and 0.917 and 0.920 for
      time to maximum landing force, respectively. The interclass correlation
      coefficients for the maximum takeoff force and time to maximum takeoff force
      during the drop vertical jump were 0.991 and 0.86. The results indicate the force
      and timing measurements from the portable force plate were both valid and
      reliable. Use of the portable force plate may facilitate methods of force
      measurement that can be applied out into the field and therefore a valuable tool
      for on site landing and jump force measurements in a variety of settings for
      large numbers of subjects.

PMID- 17194241
TI  - Anthropometric and performance variables discriminating elite American junior men
      weightlifters.
AB  - The purpose of this study is to identify physical and performance variables that
      discriminate elite American junior-aged men weightlifters from nonelite
      performers. Using a cross-sectional design, multiple discriminant analysis was
      used to determine field tests identifying elite male junior weightlifters. Young
      men who were participants (n = 115) at the Junior National and Junior Olympics
      Weightlifting Championships volunteered as subjects (mean +/- SD age = 14.8 +/-
      2.3 years). Elite weightlifters (n = 20) were identified as the top 17.5% of
      national-level competitors when weightlifting performances were adjusted for body
      mass using the Sinclair equation. All other weightlifters were classified as
      nonelite (n = 95). Test batteries were performed immediately upon completion of a
      national-level weightlifting competition. Variables measured included easily
      administered field tests of physical dimensions and body composition, muscular
      strength and power, flexibility, and gross motor control. The resulting
      regression equations correctly classified 84.35% of the weightlifters as elite or
      nonelite. Five variables significantly contributed to the discriminant analysis
      (Wilks Lambda = 0.6637392, chi(2) = 44.880, df = 5, p < 0.0001, adjusted R(2) =
      0.67). Body mass index accounted for 23.13% of the total variance, followed by
      vertical jump (22.78%), relative fat (18.09%), grip strength (14.43%), and torso
      angle during an overhead squat (0.92%). The use of these 5 easily administered
      field tests is potentially useful as a screening tool for elite American junior
      men weightlifters.

PMID- 17194242
TI  - The effects of a twenty-four-week aquatic training program on muscular strength
      performance in healthy elderly women.
AB  - The purpose of the present study was to determine the effectiveness of a 24-week
      aquatic training (AT) program, which included both aerobic and resistance
      components, on muscle strength (isometric and dynamic), flexibility, and
      functional mobility in healthy women over 60 years of age. Twenty-two subjects
      were assigned randomly to either an AT (n = 12) or a control (C, n = 10) group.
      Volunteers participated in a supervised shallow-water exercise program for 60
      minutes a day, 3 days a week; the exercise program consisted of a 10-minute warm
      up and stretching, 25 minutes of endurance-type exercise (dancing) at 80% of
      heart rate (HR)(max), 20 minutes of upper- and lower-body resistance exercises
      with specialized water-resistance equipment, and a 5-minute cool down. Maximal
      isometric torque of knee extensors (KEXT) and knee flexors (KFLEX) were evaluated
      by a Cybex Norm dynamometer, grip strength (HGR) was evaluated using a Jamar
      hydraulic dynamometer, and dynamic strength was evaluated via the 3 repetition
      maximum (3RM) test for chest press, knee extension, lat pull down, and leg press.
      Jumping performance was evaluated using the squat jump (SJ), functional mobility
      with the timed up-and-go (TUG) test, and trunk flexion with the sit-and-reach
      test. Body composition was measured using the bioelectrical impedance method. The
      AT induced significant improvements in KEXT (10.5%) and KFLEX (13.4%) peak
      torque, HGR strength (13%), 3RM (25.7-29.4%), SJ (24.6%), sit-and-reach (11.6%),
      and TUG (19.8%) performance. The AT group demonstrated a significant increase in
      lean body mass (3.4%). No significant changes in these variables were observed in
      the C group. The results indicate that AT, with both aerobic and resistance
      components, is an alternative training method for improving neuromuscular and
      functional fitness performance in healthy elderly women.

PMID- 17194243
TI  - Effects of creatine monohydrate supplementation on body composition and strength
      indices in experienced resistance trained women.
AB  - The purpose of this study was to examine 10 weeks of creatine monohydrate (Cr)
      supplementation coupled with resistance training on body composition and strength
      in women trainees. Twenty-six subjects ingested Cr (n = 13) or a placebo (Pl) (n
      = 13) at a dose of 0.3 g.kg(-1) and 0.03 g.kg(-1) body mass for the initial 7
      days and subsequent 9 weeks, respectively, while performing a resistance training
      program 4 days per week. Significant increases (p < 0.05) occurred in both groups
      for lean body mass and 1 repetition maximum (1RM) bench press and incline leg
      press. There was a significant main effect for training, but there was no
      significant difference in the total number of repetitions completed after 5 sets
      of multiple repetitions to exhaustion at 70% of 1RM for bench press and incline
      leg press for both groups or in the ability to perform a greater training volume
      (sets x repetitions x load) in the Cr vs. Pl groups over the 10 weeks. The
      results indicate that Cr supplementation combined with 10 weeks of concurrent
      resistance training may not improve strength or lean body mass greater than
      training only. These findings may be a result of nonresponders due to gender
      differences or a varying biological potential to uptake Cr within the muscle.

PMID- 17194245
TI  - The contribution of maximal force production to explosive movement among young
      collegiate athletes.
AB  - Critical to multidimensional sport conditioning is a systematic knowledge of the
      interactions between fitness components, as well as the transference
      relationships to performance. The purpose of this investigation was to examine
      the relationships between lower body muscular strength and several fundamental
      explosive performance measures. Fifty-four men and women collegiate athletes were
      tested to determine (a) lower-body muscular strength (1 repetition maximum
      barbell back squat), (b) countermovement vertical jump height and peak power
      output, (c) standing broad jump distance, (d) agility (cone T-test time), (e)
      sprint acceleration (m.s(-2)), and (f) sprint velocity (m.s(-1)). Analyses were
      performed using Pearson r correlations to examine these relationships. Partial
      correlations tested for relationships between performance measures while
      controlling for muscular strength. T-tests were performed to assess the
      difference between men and women. Correlation data demonstrated that significant
      (p < 0.01) strong linear relationships were indicated between muscular strength
      and power, as well as every sport-performance field tests. However, when
      controlling for strength with partial correlation, each of these relationships
      appreciably diminished. Significant differences (p < 0.05) were found between men
      and women for each of the performance tests. Muscular strength, peak power
      output, vertical jumping ability, standing broad jump, agility, sprint
      acceleration, and sprint velocity were all shown to be very highly related.
      Further examination demonstrated that body mass-adjusted muscular strength is
      more highly related to performance measures than is absolute muscular strength.
      Current correlation data provide a quantified look at the interaction between
      muscular fitness components, as well as the transfer relationship to several
      athletic-specific performance measures.

PMID- 17194244
TI  - Acute effects of static stretching on peak torque and mean power output in
      National Collegiate Athletic Association Division I women's basketball players.
AB  - The purpose of this study was to examine the acute effects of static stretching
      on peak torque (PT) and mean power output (MP) during maximal, voluntary
      concentric isokinetic leg extensions at 60 and 300 degrees .s(-1) in National
      Collegiate Athletic Association Division I Women's Basketball players. Eleven
      members of a women's basketball team volunteered to perform maximal concentric
      isokinetic leg extensions at 60 and 300 degrees .s(-1) on a calibrated Biodex
      System 3 dynamometer. After the initial isokinetic testing, the dominant leg
      extensors were stretched using 1 unassisted and 3 assisted static stretching
      exercises. The poststretching isokinetic assessments were repeated at 5, 15, 30,
      and 45 minutes after the static stretching (post-5, post-15, post-30, and post
      45). PT (N.m) and MP (W) were recorded by dynamometer software. The results
      indicated no stretching-related changes in PT (p = 0.161) or MP (p = 0.088) from
      pre- to poststretching for any of the testing intervals (post-5, post-15, post
      30, and post-45). These findings indicated that the static stretching had no
      impact on PT or MP during maximal, voluntary concentric isokinetic muscle actions
      in collegiate women's basketball players. In conjunction with previous studies,
      these findings suggested that trained athletes may be less susceptible to the
      stretching-induced force deficit than untrained, nonathletes.

PMID- 17194246
TI  - Acute effect of static stretching on power output during concentric dynamic
      constant external resistance leg extension.
AB  - The purpose of the present study was to clarify the effect of static stretching
      on muscular performance during concentric isotonic (dynamic constant external
      resistance [DCER]) muscle actions under various loads. Concentric DCER leg
      extension power outputs were assessed in 12 healthy male subjects after 2 types
      of pretreatment. The pretreatments included (a) static stretching treatment
      performing 6 types of static stretching on leg extensors (4 sets of 30 seconds
      each with 20-second rest periods; total duration 20 minutes) and (b)
      nonstretching treatment by resting for 20 minutes in a sitting position. Loads
      during assessment of the power output were set to 5, 30, and 60% of the maximum
      voluntary contractile (MVC) torque with isometric leg extension in each subject.
      The peak power output following the static stretching treatment was significantly
      (p < 0.05) lower than that following the nonstretching treatment under each load
      (5% MVC, 418.0 +/- 82.2 W vs. 466.2 +/- 89.5 W; 30% MVC, 506.4 +/- 82.8 W vs.
      536.4 +/- 97.0 W; 60% MVC, 478.6 +/- 77.5 W vs. 523.8 +/- 97.8 W). The present
      study demonstrated that relatively extensive static stretching significantly
      reduces power output with concentric DCER muscle actions under various loads.
      Common power activities are carried out by DCER muscle actions under various
      loads. Therefore, the result of the present study suggests that relatively
      extensive static stretching decreases power performance.

PMID- 17194247
TI  - Neuromuscular responses to three days of velocity-specific isokinetic training.
AB  - The purpose of this investigation was to examine the effects of 3 days of
      velocity-specific isokinetic training on peak torque (PT) and the
      electromyographic (EMG) signal. Thirty adult women were randomly assigned to a
      slow-velocity training (SVT), fast-velocity training (FVT), or control (CON)
      group. All subjects performed maximal, concentric, isokinetic leg extension
      muscle actions at 30 and 270 degrees .s(-1) for the determination of PT on visits
      1 (pretest) and 5 (posttest). Electromyographic signals were recorded from the
      vastus lateralis, rectus femoris, and vastus medialis muscles during each test.
      The training groups performed 4 sets of 10 maximal repetitions at 30 degrees .s(
      1) (SVT group) or 270 degrees .s(-1) (FVT group) on visits 2, 3, and 4. For the
      SVT group, PT increased from pretest to posttest at 30 and 270 degrees .s(-1).
      The increase in PT at 30 degrees .s(-1) was greater than at 270 degrees .s(-1).
      For the FVT group, PT increased at 270 degrees .s(-1) only. For the CON group,
      there were no changes in PT at either velocity. There were no pretest to posttest
      changes in EMG amplitude or mean power frequency (MPF) for any group at any
      velocity, with the exception of an increase in EMG MPF from the vastus medialis
      muscle at 270 degrees .s(-1) for the FVT group. The results indicated that 3
      sessions of slow velocity (30 degrees .s(-1)) isokinetic training resulted in an
      increase in PT at slow and fast velocities (30 and 270 degrees .s(-1)), whereas
      training at the fast velocity (270 degrees .s(-1)) increased PT only at 270
      degrees .s(-1). The lack of consistent increases in EMG amplitude or MPF
      suggested that the training-induced increases in leg extension PT were not caused
      by increased activation of the superficial muscles of the quadriceps femoris. The
      important implication for coaches, trainers, and physical therapists is that
      significant muscular performance gains may be achieved even after very short
      training periods, but determination of the specific physiological adaptation(s)
      underlying these performance gains requires further investigation.

PMID- 17194248
TI  - Ballistic stretching increases flexibility and acute vertical jump height when
      combined with basketball activity.
AB  - Stretching is often included as part of a warm-up procedure for basketball
      activity. However, the efficacy of stretching with respect to sport performance
      has come into question. We determined the effects of 4 different warm-up
      protocols followed by 20 minutes of basketball activity on flexibility and
      vertical jump height. Subjects participated in 6 weeks (2 times per week) of warm
      up and basketball activity. The warm-up groups participated in ballistic
      stretching, static stretching, sprinting, or basketball shooting (control group).
      We asked 3 questions. First, what effect does 6 weeks of warm-up exercise and
      basketball play have on both flexibility and vertical jump height? We measured
      sit and reach and vertical jump height before (week -1) and after (week 7) the 6
      weeks. Flexibility increased for the ballistic, static, and sprint groups
      compared to the control group (p < 0.0001), while vertical jump height did not
      change for any of the groups. Our second question was what is the acute effect of
      each warm-up on vertical jump height? We measured vertical jump immediately after
      the warm-up on 4 separate occasions during the 6 weeks (at weeks 0, 2, 4, and 6).
      Vertical jump height was not different for any group. Finally, our third question
      was what is the acute effect of each warm-up on vertical jump height following 20
      minutes of basketball play? We measured vertical jump height immediately
      following 20 minutes of basketball play at weeks 0, 2, 4, and 6. Only the
      ballistic stretching group demonstrated an acute increase in vertical jump 20
      minutes after basketball play (p < 0.05). Coaches should consider using ballistic
      stretching as a warm-up for basketball play, as it is beneficial to vertical jump
      performance.

PMID- 17194249
TI  - The decline of swimming performance with advancing age: a cross-sectional study.
AB  - The aim of this cross-sectional study was to measure the swimming parameters
      speed (V), stroke frequency (SF), and stroke length (SL)- in 162 male athletes
      aged 50-90 (divided into 7 age groups, from A to G) participating in the World
      Master Championships in the 200-m freestyle event, and to analyze the rates and
      magnitudes of their age-associated declines. The swimmers were video-recorded by
      2 digital cameras during the competitions and the swimming parameters related to
      every 50-m section (lap) and to the entire race (average) subsequently measured
      or calculated. Lap V and SF decreased in the second and third quarter (11 and 4%
      on average) and increased (3% on average) in the fourth quarter of the race,
      whereas lap SL decreased from the first to the last 50-m section. Average V (m.s(
      1)) decreased from 1.39 +/- 0.09 (group A) to 0.84 +/- 0.11 (group G); average SL
      (m) decreased from 2.10 +/- 0.20 (group A) to 1.78 +/- 0.19 (group G); and
      average SF (cycles.s(-1)) decreased from 0.67 +/- 0.06 (group A) to 0.47 +/- 0.04
      (group G). One-way analysis of variance showed significant declines in average V,
      SL, and SF (p < 0.01) across the 7 groups. The swimming parameters were
      normalized to the highest values (set equal to 100); thereafter, a linear
      regression curve was fitted and the regression equations calculated. Decline of
      SF was about 2.5 times steeper than that of SL. It was highlighted that (a) among
      the swimming parameters, SL is less affected by the ageing process; (b) SL
      decreased from group A through group C and thereafter tended to keep steady,
      whereas the trend for SF was opposite. The results have the potential to give
      master swimmers and their coaches useful information for training program design.

PMID- 17194250
TI  - Effects of age on testosterone responses to resistance exercise and
      musculoskeletal variables in men.
AB  - This study compared serum total testosterone (TT) and free testosterone (FT)
      responses of young (20-26 years, n = 8), middle-aged (38-53 years, n = 7), and
      older (59-72 years, n = 9) men to resistance exercise. We also examined the
      relationships between testosterone (T) levels and strength, bone mineral density
      (BMD), and body composition variables for each age group. Subjects were tested
      for isotonic muscular strength (1 repetition maximum [1RM]), BMD (dual-energy x
      ray absorptiometry [DXA]) and body composition (DXA). Each group performed an
      acute exercise protocol (3 sets, 10 repetitions, 80% of 1RM, 6 exercises). Blood
      samples were obtained at baseline, immediately postexercise, and 15 minutes
      postexercise for the TT and FT assays. The older age group had significantly (p <
      0.05) lower T levels than the young group, but each group exhibited an increase
      (p < 0.05) in TT and FT immediately postexercise. Total T and FT were
      significantly correlated (p < 0.05) with strength in middle-aged and older men
      and with bone-free lean tissue mass in older men. In conclusion, middle-aged and
      older men showed similar relative T responses to those of younger men to a single
      bout of high-intensity resistance exercise. However, T levels were related to
      strength and muscle mass only in middle-aged or older men. On a practical
      application level, older men can complete a high-intensity resistance exercise
      program resulting in spikes in T that may attenuate age-related muscle and BMD
      loss.

PMID- 17194251
TI  - Predicting maximal strength in trained postmenopausal woman.
AB  - The purpose of this study was to present an equation that accurately predicts 1
      repetition maximum (RM) over a wide range of repetitions to fatigue (RTF) for 4
      different machine resistance exercises in postmenopausal women. Seventy trained
      women (age = 57.4 +/- 3.1 years) performed maximal and submaximal repetitions on
      leg press, bench press, rowing, and leg adduction machines at the conclusion of a
      2-year training program. Maximal repetitions were performed on each exercise in
      the following ranges: 3-5RM, 6-10RM, 11-15RM, and 16-20RM. Special regard was
      taken to maintain the identical execution of each test (i.e., range of motion,
      starting angle, speed of movement). One cubic polynomial (w(i) [0.988-0.0000584
      r(i)(3) + 0.00190 r(i)(2) + 0.0104 r(i),] where w(i) is the load of measurement
      I, and r(i) is the number of repetitions) accurately predicted 1RM from RTF with
      mean absolute differences between actual 1RM and predicted 1RM for the 4
      exercises of 1.5-3.1% and with coefficients of variation of <3.3%. Equation
      accuracy was independent of the exercise type or the number of RTF. Thus, this
      study supported the validity of RTF to adequately estimate 1RM over a wide range
      of repetitions and within different exercises in trained, older female subjects.

PMID- 17194252
TI  - Eccentric utilization ratio: effect of sport and phase of training.
AB  - The eccentric utilization ratio (EUR), which is the ratio of countermovement jump
      (CMJ) to static jump (SJ) performance, has been suggested as a useful indicator
      of power performance in athletes. The purpose of the study was to compare the EUR
      of athletes from a variety of different sports and during different phases of
      training. A total of 142 athletes from rugby union, Australian Rules Football,
      soccer, softball, and field hockey were tested. Subjects performed both CMJ and
      SJ on a force plate integrated with a position transducer. The EUR was measured
      as the ratio of CMJ to SJ for jump height and peak power. The rugby union,
      Australian Rules Football, and hockey athletes were tested during off-season and
      preseason to provide EUR data during different phases of training. For men, EUR
      for soccer, Australian Rules Football, and rugby was greater than softball
      (effect size range, 0.83-0.92). For women, EUR for soccer was greater than field
      hockey and softball (0.86- 1.0). There was a significant difference between the
      jump height and peak power method for the Australian Rules Football, rugby, and
      field hockey tests conducted preseason (p < 0.05). For field hockey, there was a
      significant increase in EUR from off-season to preseason. Athletes in sports such
      as soccer, rugby union, and Australian Rules Football appear to have higher EUR
      values, which reflects the greater reliance on stretch shortening activities in
      these sports. It does appear that EUR can be used to track changes in training
      with the values significantly increasing from off-season to preseason. The EUR
      provides the practitioner with information about the performance of athletes and
      appears to be sensitive to changes in the type of training being undertaken.

PMID- 17194253
TI  - Isometric squat force output and muscle activity in stable and unstable
      conditions.
AB  - The purpose of this study was to assess the effect of stable vs. unstable
      conditions on force output and muscle activity during an isometric squat. Nine
      men involved in recreational resistance training participated in the
      investigation by completing a single testing session. Within this session
      subjects performed isometric squats either while standing directly on the force
      plate (stable condition, S) or while standing on inflatable balls placed on top
      of the force plate (unstable condition, U). Electromyography (EMG) was recorded
      during both conditions from the vastus lateralis (VL), vastus medialis (VM),
      biceps femoris (BF), and medial gastrocnemius (G) muscles. Results indicated peak
      force (PF) and rate of force development (RFD) were significantly lower, 45.6%
      and 40.5% respectively, in the U vs. S condition (p < or = 0.05). Average
      integrated EMG values for the VL and VM were significantly higher in the S vs. U
      condition. VL and VM muscle activity was 37.3% and 34.4% less in U in comparison
      to S. No significant differences were observed in muscle activity of the BF or G
      between U and S. The primary finding in this investigation is that isometric
      squatting in an unstable condition significantly reduces peak force, rate of
      force development, and agonist muscle activity with no change in antagonist or
      synergist muscle activity. In terms of providing a stimulus for strength gain no
      discernable benefit of performing a resistance exercise in an unstable condition
      was observed in the current study.

PMID- 17194254
TI  - A brief review of concurrent activation potentiation: theoretical and practical
      constructs.
AB  - Enhancing the acute quality of the resistance training stimulus is the goal of
      many research and applied professionals. To that end, many methods have been
      proposed and a variety of training strategies and ergogenic supplements have been
      investigated. Postactivation potentiation is one phenomenon that has been
      frequently examined, offering some promise in this regard. Though never
      previously applied in the strength and conditioning profession, dental research
      on jaw clenching, studies examining the Jendrassik maneuver and remote voluntary
      contractions and research on motor overflow together make a compelling case for
      the existence of a concurrent activation potentiation phenomenon and the acute
      ergogenic advantage associated with the simultaneous activation of muscles other
      than the prime mover or synergists. Evidence demonstrates that this advantage is
      accrued via activation of the H reflex and through cortical overflow. Ultimately,
      through research and practical application, athletes may be taught to optimize
      the type, timing, and magnitude of remote muscle actions in order to gain an
      ergogenic advantage and increase the acute response of the prime movers. This
      strategy may be especially useful during the most difficult portion of a
      resistance training repetition and during the most difficult repetitions of a
      resistance training set.

PMID- 17194255
TI  - Effects of twenty-eight days of beta-alanine and creatine monohydrate
      supplementation on the physical working capacity at neuromuscular fatigue
      threshold.
AB  - The purpose of this study was to examine the effects of 28 days of beta-alanine
      (b-Ala) and creatine monohydrate (CrM) supplementation on the onset of
      neuromuscular fatigue by using the physical working capacity at neuromuscular
      fatigue threshold (PWC(FT)) test in untrained men. Fifty-one men (mean age +/- SD
      = 24.5 +/- 5.3 years) volunteered to participate in this 28-day, double-blind,
      placebo-controlled study and were randomly assigned to 1 of 4 groups: placebo
      (PLA; 34 g dextrose; n = 13), CrM (5.25 g CrM plus 34 g dextrose; n = 12), b-Ala
      (1.6 g b-Ala plus 34 g of dextrose; n = 12), or b-Ala plus CrM (CrBA; 5.25 g CrM
      plus 1.6 g b-Ala plus 34 g dextrose; n = 14). The supplement was ingested 4 times
      per day for 6 consecutive days, then twice per day for 22 days before
      posttesting. Before and after the supplementation, subjects performed a
      continuous incremental cycle ergometry test while a surface electromyographic
      signal was recorded from the vastus lateralis muscle to determine PWC(FT). The
      adjusted mean posttest PWC(FT) values (covaried for pretest PWC(FT) values) for
      the b-Ala and CrBA groups were greater than those for the PLA group (p < or =
      0.05). However, there were no differences between the CrM vs. PLA, CrBA vs. b
      Ala, CrM vs. b-Ala, or CrM vs. CrBA groups (p > 0.05). These findings suggested
      that b-Ala supplementation may delay the onset of neuromuscular fatigue.
      Furthermore, there appeared to be no additive or unique effects of CrM vs. b-Ala
      alone on PWC(FT).

PMID- 17194257
TI  - Four weeks of optimal load ballistic resistance training at the end of season
      attenuates declining jump performance of women volleyball players.
AB  - Anecdotal and research evidence is that vertical jump performance declines over
      the competitive volleyball season. The purpose of this study was to evaluate
      whether a short period of ballistic resistance training would attenuate this
      loss. Fourteen collegiate women volleyball players were trained for 11 weeks with
      periodized traditional and ballistic resistance training. There was a 5.4%
      decrease (p < 0.05) in approach jump and reach height during the traditional
      training period (start of season to midseason), and a 5.3% increase (p < 0.05)
      during the ballistic training period (midseason to end of season), but values
      were not different from start to end of season. These changes in overall jump
      performance were reflective of changes in underlying neuromuscular performance
      variables: in particular, power output and peak velocity during loaded jump
      squats, countermovement jumps, and drop jumps. During the first 7 weeks of
      traditional heavy resistance training, it appears that the neuromuscular system
      is depressed, perhaps by the combination of training, game play, and skills
      practice precluding adequate recovery. Introduction of a novel training stimulus
      in the form of ballistic jump squats and reduction of heavy resistance training
      of the leg extensors stimulated a rebound in performance, in some cases to exceed
      the athlete's ability at the start of the season. Periodization of in-season
      training programs similar to that used in this study may provide volleyball
      players with good vertical jump performance for the crucial end-of-season games.

PMID- 17194256
TI  - Determination of functional strength imbalance of the lower extremities.
AB  - The purposes of this study were (a) to determine whether a significant strength
      imbalance existed between the left and right or dominant (D) and nondominant (ND)
      legs and (b) to investigate possible correlations among various unilateral and
      bilateral closed kinetic chain tests, including a field test, and traditional
      isokinetic dynamometry used to determine strength imbalance. Fourteen Division I
      collegiate women softball players (20.2 +/- 1.4 years) volunteered to undergo
      measures of average peak torque for isokinetic flexion and extension at 60
      degrees .s(-1) and 240 degrees .s(-1); in addition, measures of peak and average
      force of each leg during parallel back squat, 2-legged vertical jump, and single
      leg vertical jump and performance in a 5-hop test were examined. Significant
      differences of between 4.2% and 16.0% were evident for all measures except for
      average force during single-leg vertical jump between the D and ND limbs, thus
      revealing a significant strength imbalance. The 5-hop test revealed a significant
      difference between D and ND limbs and showed a moderate correlation with more
      sophisticated laboratory tests, suggesting a potential use as a field test for
      the identification of strength imbalance. The results of this study indicate that
      a significant strength imbalance can exist even in collegiate level athletes, and
      future research should be conducted to determine how detrimental these imbalances
      could be in terms of peak performance for athletes, as well as the implications
      for injury risk.

PMID- 17194258
TI  - Kinematical analysis of the snatch in elite male junior weightlifters of
      different weight categories.
AB  - The purpose of this study was to analyze the differences in the technical pattern
      of the snatch in elite junior weightlifters of different weight categories. The
      sample was a group of 33 men weightlifters from different weight categories. The
      comparative study included 2 groups, taking into account weight categories. Group
      A included 17 weightlifters from the lightest categories, 56 and 62 kg; group B
      included 16 weightlifters from the heaviest categories, 85 and 105 kg. Three
      dimensional photogrammetry technique was utilized. Regarding group differences,
      we can conclude that lifters belonging to heavier categories are more efficient,
      as they manage to have longer barbell propulsion trajectories, which allows them
      to exert actions on the barbell for a longer period, especially in the initial
      lifting phase. They attain greater barbell vertical velocity (p = 0.029), a
      longer vertical bar trajectory normalized on first pull (p = 0.011), and a
      greater, although limited, bar height loss on the catch (p = 0.008). Besides,
      intergroup differences evidence that heavier category lifters observe a different
      temporal organization of the movement based on a longer first pull (p = 0.000), a
      shorter transition (p = 0.030), and a longer turnover (p = 0.049). No significant
      differences were found in the analyzed angular parameters during the first and
      second pull. We believe the intergroup differences found not to be determining
      enough to consider a technical model adapted to the characteristics of each body
      weight category. This confirms that a successful lift is multifactor based and
      individual dependent. Given its transcendence, this evidence should be taken into
      account in the technical training of young lifters.

PMID- 17194260
TI  - The failure of evidence-based medicine to guide treatment of antidepressant
      nonresponders.

PMID- 17194261
TI  - Switching antidepressants after a first selective serotonin reuptake inhibitor in
      major depressive disorder: a systematic review.
AB  - OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are frequently used as
      a first antidepressant for major depressive disorder but have response rates of
      50% to 60% in daily practice. For patients with insufficient response to SSRIs,
      switching is often applied. This article aims to systematically review the
      evidence for switching pharmacotherapy after a first SSRI. DATA SOURCES: A
      systematic literature search (updated until Feb. 10, 2005) in MEDLINE, EMBASE,
      CINAHL, and PsychINFO (all indexed years) identified randomized, controlled
      trials (RCTs) and open studies investigating switching strategies. In the absence
      of specific keywords for switching, we performed "sensitive" searches using free
      text words with wildcards ($): "switch$" or ("alternat$" adj5 "treat$") or
      ("alternat$" adj5 "therap$") in combination with the Cochrane Collaboration
      search filter for RCTs, the Cochrane Collaboration Depression Anxiety and
      Neurosis Group search filter for major depressive disorder, and MeSH terms for
      antidepressants (in combination with additional text words for all antidepressive
      agents). Additionally, we included 4 recent Sequenced Treatment Alternatives to
      Relieve Depression publications. We limited searches to adults and humans but did
      not apply language restrictions. STUDY SELECTION: Relevant articles were
      retrieved and critically appraised. The methodology of the studies, the results
      on efficacy and dropouts due to side effects, and remarks were summarized in an
      evidence table. Three studies comparing a switch to venlafaxine or SSRIs were
      pooled. DATA SYNTHESIS: Eight RCTs and 23 open studies were identified, studying
      populations with different levels of treatment resistance. Definitions of
      response and remission rates varied between studies. Observed response rates
      after switching to any of the classes of antidepressants varied between 12% and
      86%. Remission rates varied between 7% and 82%. The number of previous treatments
      with antidepressants was negatively correlated with treatment outcome. Rates of
      dropout due to side effects varied considerably across agents (5%-39%). Switching
      to venlafaxine showed a modest and clinically equivocal benefit over SSRIs
      (number needed to treat = 13 [95% CI = 9.1 to 25.0]). CONCLUSIONS: After a first
      SSRI, any switch within or between classes of antidepressants appears legitimate
      (second SSRI, novel dual-acting antidepressants, selective norepinephrine or nor
      adrenergic/dopaminergic agents, or tricyclic anti-depressant or mianserin). No
      unequivocal evidence is available to prove an advantage of a between-class
      switch. More guidance by randomized empirical studies is needed. Clinical
      implications and methodological considerations for future studies are discussed.

PMID- 17194262
TI  - Improved insulin sensitivity in 80 nondiabetic patients with MDD after clinical
      remission in a double-blind, randomized trial of amitriptyline and paroxetine.
AB  - OBJECTIVE: There is substantial evidence that depression constitutes a risk
      factor for type 2 diabetes mellitus. A recent study has shown that high salivary
      cortisol levels are associated with decreased insulin sensitivity in unmedicated,
      depressed patients. Further, antidepressive treatment might have differential
      effects on hypothalamus-pituitary-adrenal (HPA) system activity. Therefore, the
      aim of the present study was to examine whether insulin sensitivity improves
      during anti-depressive treatment in depressed patients with declining HPA system
      activity. METHOD: Eighty inpatients with an episode of major depressive disorder
      (DSM-IV criteria) were treated in a double-blind, randomized protocol with either
      amitriptyline or paroxetine over a period of 5 weeks. After 6 drug-free days, an
      oral glucose tolerance test was performed on day 1 and again 35 days after
      antidepressive treatment. For quantification of free cortisol levels, saliva was
      obtained daily at 8:00 a.m. during weeks -1 (washout) and 5. The study was
      conducted from May 2005 to December 2005. RESULTS: The insulin sensitivity
      index(Matsuda) increased in only those patients who remitted from major
      depressive disorder as a result of treatment with either antidepressant (F = 7.0,
      df = 1,74; p < .01), while correcting for body mass index. Further, cortisol
      concentrations declined in remitters and responders to amitriptyline (F = 2.1, df
      = 1,70; p < .05), but not in any other subgroup. CONCLUSION: Successful
      antidepressive treatment with either a selective serotonin reuptake inhibitor or
      a tricyclic substance increases the sensitivity to insulin in nondiabetic
      depressed patients. The herein presented longitudinal data do not exclude the HPA
      system as a major contributor to insulin resistance in depressed patients, but
      underscore the assumption of additional factors.

PMID- 17194263
TI  - Psychiatry and psychology in medieval Persia.
AB  - OBJECTIVE: The history of psychological sciences and especially the ways in which
      related disorders were treated in medieval Persia are not well known in the West.
      The main objective of this article is to review the clinical approaches to
      psychological disorders used by practitioners in medieval Persia. DATA SOURCES:
      Several documents still exist from which the clinical data on different
      psychological syndromes in medieval Persia can be ascertained. Data for this
      review were identified by searches of MEDLINE, Current Contents, the Internet,
      references from relevant articles and books, the Astan-e-Ghods Razavi Library,
      the Tehran University Library, the Mashhad University Library, and the files of
      the authors. Search terms included psychiatry, psychology, Persian, medieval,
      Avicenna, and pharmacotherapy. DISCUSSION: The medieval practitioners defined
      various signs and symptoms, apparent causes, and hygienic and dietary rules for
      prevention of these disorders. Medieval Persian medical writings encouraged the
      treatment of psychological disorders by tackling the conditions that cause or
      contribute to the disorder and through the use of electrical-shock therapy,
      phlebotomy, psychotherapy, music and color therapy, and especially prescription
      of long lists of medicaments. CONCLUSION: Some of the approaches of doctors in
      medieval Persia are accepted today, although most remain largely unexamined. With
      further research, more of these treatments may be shown to be of use to modern
      medicine.

PMID- 17194264
TI  - Factors modifying the efficacy of transcranial magnetic stimulation in the
      treatment of depression: a review.
AB  - OBJECTIVE: So far no convincing answer has emerged to the question of whether
      transcranial magnetic stimulation (TMS) can make a clinically useful contribution
      to the treatment of depression. Here we examine whether multiple sensitivity
      analyses can highlight parameters that predict a favorable treatment response.
      DATA SOURCES: Medline, Embase, and the Cochrane database for controlled trials
      were searched for relevant randomized controlled trials using the expression
      (transcranial magnetic stimulation or TMS) and depression. STUDY SELECTION:
      Thirty-three studies were identified and included in the random-effects meta
      analysis, and between 17 and 31 studies were included in the secondary analyses
      comparing outcome of studies with different parameters. DATA EXTRACTION: Study
      data were extracted with a standardized data sheet. A meta-analysis based on
      Cohen d effect size measure was done for all studies and various subsets.
      Regression analysis of effect sizes with study parameters was done in 24 studies.
      DATA SYNTHESIS: Active TMS treatment was more effective than sham, but
      variability was too great to take any single study design as paradigmatic. No
      significant predictors of study effect size were found. Mean effect sizes were
      reduced, although still significant, in studies with stimulation intensity below
      90% of motor threshold and new medication starting within 7 days before to 7 days
      after start of TMS. CONCLUSIONS: The absence of significant outcome predictors in
      the presence of significant variability of outcome measures can be interpreted in
      2 ways: either study sizes and numbers and designs are insufficient to afford the
      power necessary to detect such predictors or TMS has a nonspecific effect on
      depression that is not influenced by study parameters. Large-scale comparative
      trials are necessary to decide between these interpretations.

PMID- 17194265
TI  - The Trichotillomania Impact Project (TIP): exploring phenomenology, functional
      impairment, and treatment utilization.
AB  - BACKGROUND: Trichotillomania (TTM) occurs in 0.6% to 3.4% of adults. Questions
      remain about phenomenological features of the disorder, its impact on
      functioning, and treatment utilization. The current study (i.e., The
      Trichotillomania Impact Project) was designed to provide initial information
      regarding these issues. METHOD: An Internet-based survey was completed by 1697
      individuals who self-reported symptoms consistent with a diagnosis of TTM (DSM-IV
      TR). The survey assessed phenomenological experiences; social, occupational,
      academic, and psychological impact; as well as treatment-seeking experiences. The
      survey link operated from April 2005 through May 2005. RESULTS: Survey results
      suggest considerable variability in TTM phenomenology. Individuals with more
      severe TTM symptoms endorsed more frequent phenomenological experiences of
      physical or mental anxiety prior to pulling and relief, pleasure, or
      gratification after pulling. Mild to moderate life impairment in social,
      occupational, academic, and psychological functioning was reported for the entire
      study sample. These impairments were more pronounced as TTM symptoms became more
      severe. A summary of treatment seeking in the sample suggests that
      pharmacotherapy was the most commonly received treatment, followed by behavior
      therapy. Unfortunately, treatment in general was perceived as relatively
      ineffective. CONCLUSION: This study underscores the clinical significance of
      severe hair pulling and highlights the need for research on its pathogenesis and
      treatment.

PMID- 17194266
TI  - Treatment with rosuvastatin for severe dyslipidemia in patients with
      schizophrenia and schizoaffective disorder.
AB  - BACKGROUND: Mortality rates in patients with schizophrenia are double compared to
      those in the general population, with cardiovascular disease causing 50% of the
      excess. Lowering low-density lipoprotein (LDL) cholesterol is recognized as a
      primary target for the prevention of cardiovascular mortality according to the
      National Cholesterol Education Program-Adult Treatment Panel III. Use of lipid
      lowering drugs such as statins is recommended when lifestyle changes are not
      sufficient to reach the LDL goal. The efficacy and safety of rosuvastatin
      treatment were evaluated in schizophrenic patients. METHOD: 100 schizophrenic
      patients with severe dyslipidemia were identified. All were treated with
      antipsychotics. Fifty-two patients were treated with rosuvastatin and compared
      with 48 who did not receive statin treatment. All patients were screened for
      cardiovascular risk factors and examined at baseline. The effects of lipid
      lowering medication on lipid profile, glucose homeostasis, and components of
      metabolic syndrome were evaluated at 3-month follow-up. The study began in 2003,
      and all data available until December 2005 are reported. RESULTS: After 3 months
      of statin therapy, a significant decrease in triglycerides, total cholesterol,
      LDL cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol and in
      associated ratios (LDL/HDL, total cholesterol/HDL) was observed. The difference
      was highly significant compared to patients not receiving statin treatment. No
      significant changes occurred in HDL cholesterol, body mass index and waist
      circumference, or glucose homeostasis. The only component of metabolic syndrome
      affected by statin therapy was the serum triglyceride level. CONCLUSION:
      Rosuvastatin proved effective in the management of dyslipidemia in patients with
      schizophrenia treated with antipsychotics. More complex treatment may be required
      for associated metabolic disturbances.

PMID- 17194267
TI  - Zonisamide in the treatment of binge eating disorder with obesity: a randomized
      controlled trial.
AB  - OBJECTIVE: Binge eating disorder (BED) is associated with obesity. Zonisamide is
      a novel antiepileptic drug associated with weight loss. The purpose of this study
      was to evaluate zonisa-mide in the treatment of BED associated with obesity.
      METHOD: In this 16-week, single-center, randomized, double-blind, placebo
      controlled, flexible-dose (100-600 mg/day) trial, 60 outpatients with DSM-IV-TR
      BED received zonisamide (N = 30) or placebo (N = 30). The primary outcome measure
      was weekly frequency of binge eating episodes. The primary analysis of efficacy
      was a longitudinal analysis of the intent-to-treat sample, with treatment-by-time
      interaction as the effect measure. Patients were enrolled from September 5, 2003,
      through October 1, 2004. RESULTS: Compared with placebo, zonisamide was
      associated with a significantly greater rate of reduction in binge eating episode
      frequency (p = .021), body weight (p < .001), BMI (p = .001), and scores on the
      Clinical Global Impressions-Severity scale (p < .001), Yale-Brown Obsessive
      Compulsive Scale Modified for Binge Eating (p < .001), and Three Factor Eating
      Questionnaire disinhibition scales (p < .001). Plasma ghrelin concentrations
      increased with zonisamide but decreased with placebo (p = .001). The mean (SD)
      zonisamide daily dose at endpoint evaluation was 436 (159) mg/day. Twelve
      patients (N = 8 receiving zonisamide, N = 4 receiving placebo) discontinued
      because of adverse events. The most common reasons for discontinuing zonisamide
      were accidental injury with bone fracture (N = 2), psychological complaints (N =
      2), and cognitive complaints (N = 2). CONCLUSION: Zonisamide was efficacious, but
      not well tolerated, in the short-term treatment of BED associated with obesity.
      CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00221442.

PMID- 17194268
TI  - The relationship between smoking and suicidal behavior, comorbidity, and course
      of illness in bipolar disorder.
AB  - OBJECTIVES: The rate of smoking in people with bipolar disorder is much greater
      than in the general population, but the implications of smoking for the course of
      bipolar disorder have not been well studied. The purpose of this retrospective
      study was to examine the relationship between smoking, severity of bipolar
      disorder, suicidal behavior, and psychiatric and substance use disorder
      comorbidity. METHOD: We evaluated 399 outpatients with bipolar disorder who were
      treated in a bipolar specialty clinic from December 1999 to October 2004.
      Diagnosis, mood state, course of illness, functioning, and psychiatric
      comorbidities were assessed using the Affective Disorders Evaluation and the Mini
      International Neuropsychiatric Interview. RESULTS: Of the 399 patients evaluated,
      155 (38.8%) had a history of daily smoking. Having ever smoked was associated
      with earlier age at onset of first depressive or manic episode, lower Global
      Assessment of Functioning scores, higher Clinical Global Impressions-Bipolar
      Disorder scale scores, lifetime history of a suicide attempt (47% for smokers vs.
      25% for those who had never smoked), and lifetime comorbid disorders: anxiety
      disorders, alcohol abuse and dependence, and substance abuse and dependence. In a
      logistic regression model including these factors, suicide attempts and substance
      dependence were significantly associated with smoking in patients with bipolar
      disorder. CONCLUSIONS: Bipolar patients with lifetime smoking were more likely to
      have earlier age at onset of mood disorder, greater severity of symptoms, poorer
      functioning, history of a suicide attempt, and a lifetime history of comorbid
      anxiety and substance use disorders. Smoking may be independently associated with
      suicidal behavior in bipolar disorder.

PMID- 17194269
TI  - A double-blind study of combination of clozapine with risperidone in patients
      with schizophrenia: effects on cognition.
AB  - BACKGROUND: Atypical antipsychotic drugs produce improvement in some domains of
      cognition as well as psychopathology in patients with schizophrenia. However, the
      effect of combinations of atypical antipsychotic drugs on cognitive function is
      unknown. The aim of this study was to compare the effect of risperidone or
      placebo on cognitive function in patients with schizophrenia who were previously
      treated with clozapine monotherapy. METHOD: This prospective, randomized, double
      blind, placebo-controlled, 6-week study included 30 patients with DSM-IV
      schizophrenia. Patients whose psychopathology was no more than partially
      responsive to clozapine treatment were randomly assigned to receive adjunctive
      treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive
      test scores for verbal learning and memory, verbal fluency, attention, executive
      function, verbal working memory, and motor function were the primary outcome
      measures. Secondary outcome measures included assessment of psychopathology,
      extrapyramidal side effects, and global functioning. Data were collected between
      November 2001 and July 2003. RESULTS: Significant improvement was found in both
      treatment groups in a variety of cognitive measures, but there was significantly
      greater improvement in the placebo-augmented group on measures of initial
      learning acquisition and attention. The improvement in cognition was not
      correlated with improvement in psychopathology. There were significant
      correlations between improvement in verbal working memory, verbal learning and
      memory, and attention and quality of life and global functioning in the placebo
      augmented but not the risperidone-augmented group. CONCLUSION: Adjunctive
      treatment with risperidone for 6 weeks in patients with schizophrenia who had
      received chronic treatment with clozapine does not significantly improve
      cognitive function.

PMID- 17194270
TI  - Incidence of tardive dyskinesia and tardive dystonia in African Caribbean
      patients on long-term antipsychotic treatment: the Curacao extrapyramidal
      syndromes study V.
AB  - OBJECTIVE: Tardive dyskinesia (TD) and tardive dystonia (TDt) syndromes represent
      severe side effects of first-generation antipsychotics (FGAs). Although second
      generation antipsychotics (SGAs) confer a lower risk for tardive syndromes, many
      patients continue to use FGAs alone or in combination with SGAs. Some patients
      remain free of TD or TDt even after many years of antipsychotic treatment with
      predominantly FGAs. Do these patients remain at risk for TD or TDt and,
      consequently, should a switch to SGAs be considered? A longitudinal cohort study
      in patients on long-term antipsychotic treatment may answer this question.
      METHOD: A 9-year cohort study (1992-2001) was conducted of the whole, mostly
      chronic, psychiatric inpatient population on the Caribbean island of Curacao (N =
      194). Almost all patients (95%) were of African Carribean origin. TD and TDt were
      assessed (1 baseline, 6 follow-ups) with the Abnormal Involuntary Movement Scale
      and the Fahn-Marsden rating scale, respectively. New cases of TD or TDt were
      diagnosed if they fulfilled the criteria at 2 successive follow-up visits.
      RESULTS: In patients with a mean antipsychotic use of approximately 18 years, the
      yearly incidence rates of TD and TDt were 10.2% (95% CI = 7.7 to 13.5) and 0.7%
      (95% CI = 0.4 to 1.5), respectively. The severity of TD was strongly associated
      with the severity of TDt (beta = 0.08, 95% CI = 0.03 to 0.14) and vice versa
      (beta = 0.10, 95% CI = 0.03 to 0.16). TD severity was positively associated with
      age and akathisia but negatively associated with parkinsonism. CONCLUSIONS:
      Patients who are free of TD after many years of antipsychotic treatment still
      have a considerable risk for TD. Switching to an SGA may be warranted. The risk
      for incident TDt in this group was very low.

PMID- 17194271
TI  - The prognostic significance of regular binge eating in extremely obese gastric
      bypass patients: 12-month postoperative outcomes.
AB  - OBJECTIVE: The prognostic significance of binge eating for extremely obese
      patients who undergo bariatric surgery is uncertain. We examined the relation of
      preoperative binge eating to preoperative presentation and 12-month postoperative
      outcomes. METHODS: 139 extremely obese gastric bypass surgery patients completed
      assessments of binge eating and eating disorders (Eating Disorder Examination
      Questionnaire version), body dissatisfaction (Body Shape Questionnaire),
      depression (Beck Depression Inventory), and self-esteem (Rosenberg Self-Esteem
      Scale) before surgery and again 12 months postsurgery. RESULTS: At baseline, 60%
      of patients denied binge eating, 16% reported binge eating infrequently (less
      than once weekly), and 24% reported binge eating at least weekly. At 12 months
      postsurgery, 8.8% reported infrequent binge eating and only 0.7% reported binge
      eating weekly. At baseline, infrequent binge eaters and regular binge eaters
      differed little from each other but had significantly elevated eating and
      psychosocial problems relative to non-binge eaters. Statistically significant and
      clinically robust improvements in weight and in all measures of functioning were
      observed at 12 months postsurgery across all groups. At 12-month follow-up,
      patients who reported regular binge eating at baseline had significantly higher
      levels of eating-specific concerns (but not psychosocial concerns) than the
      infrequent binge eaters and non-binge eaters; the infrequent and non-binge eaters
      did not differ from each other. Significant time-by-binge eating interactions
      indicated that the regular versus infrequent binge-eating groups improved
      differently over time; infrequent binge eaters had sharper improvements than
      regular binge eaters and non-binge eaters. CONCLUSION: Binge eating is common in
      extremely obese bariatric surgery candidates and is associated with heightened
      eating and psychological problems. Regular binge eating preoperatively, however,
      does not appear to be a potent negative prognostic indicator for gastric bypass
      surgery. Our findings, which are limited to 12 months postsurgery, highlight
      substantial improvements in weight and psychosocial functioning, and these robust
      improvements differ little by binge-eating status.

PMID- 17194272
TI  - Trends in suicide risk associated with hospitalized psychiatric illness: a case
      control study based on Danish longitudinal registers.
AB  - OBJECTIVE: In light of the consistent reduction in suicide rate during the past
      20 years in Denmark, this study aims to investigate trends in suicide risk
      associated with hospitalized psychiatric illness and to explore differences in
      the changes with regard to clinical phases of illness, sex, age, and diagnosis.
      METHOD: This population-based study includes all of 21,169 suicides in Denmark
      during the years 1981 through 1997 and 423,128 controls matched for sex, age, and
      time (using a nested case-control design). Personal data on psychiatric history
      and socioeconomic status were retrieved from Danish longitudinal registers. Data
      were analyzed using conditional logistic regression. RESULTS: This study shows
      that the reduction in suicide rate is generally faster among individuals with a
      history of psychiatric admission than among individuals without such a history.
      However, this substantial reduction is mainly accounted for by the reduction
      among patients who had been discharged from psychiatric hospitals for more than 1
      year. For patients who had been discharged from hospitals within 1 year, the
      reduction is similar to that of the general population; while for patients
      hospitalized for treatment at the time of suicide or the index date, the
      reduction in suicide rate is relatively slower. Such trends hold for all
      diagnostic groups. Further analyses stratified by age indicate that the faster
      reduction in suicide rate associated with history of hospitalized psychiatric
      illness is more pronounced among patients aged 36 years and older. CONCLUSION:
      The reduction in suicide rate is substantial for patients who have been
      discharged from psychiatric hospitals for more than 1 year and for middle-aged
      and older patients. Recent improvement in psychiatric care and treatment and
      promotion of new generation antidepressants may contribute to these changes.

PMID- 17194273
TI  - Relapse rates in patients with schizophrenia receiving aripiprazole in comparison
      with other atypical antipsychotics.
AB  - OBJECTIVE: Aripiprazole is the first of a new generation of antipsychotics that
      possesses a unique mechanism of action as a partial dopamine agonist. After the
      release of aripiprazole, case reports appeared conveying an acute
      psychosis/agitation reaction occurring after the initiation of treatment, most
      specifically after patients were switched from a previous antipsychotic to
      aripiprazole. The primary objective of this study was to compare relapse rates
      among patients with schizophrenia who were switched to aripiprazole with those
      who switched to a second-generation antipsychotic (SGA) from another
      antipsychotic. METHOD: The design was a retrospective cohort study based on
      Kansas Medicaid enrollees with an ICD-9-CM diagnosis code for schizophrenia
      during calendar year 2002 who switched antipsychotic agents. Six-month
      psychiatric relapse rates, defined as hospitalization for a psychiatric event,
      were compared between those subjects who switched to aripiprazole and those who
      switched to another SGA. Time to relapse was modeled using Cox proportional
      hazards, adjusting for demographic characteristics, major comorbid conditions,
      and prior psychiatric-related health care use. RESULTS: Four hundred forty-four
      aripiprazole and 521 SGA switchers were comparable with respect to gender, race,
      comorbidities, and health care utilization, though the aripiprazole group was 4.5
      years younger. Twenty percent of aripiprazole patients and 19.4% of patients
      receiving SGAs were hospitalized 6 months after being switched (relative risk =
      0.92; 95% CI = 0.67 to 1.26). Mean times to psychiatric hospitalization for the
      aripiprazole and SGA groups were 65.7 and 73.8 days, respectively (p > .05).
      Factors associated with hospitalization were prior psychiatric hospitalizations
      and comorbid depression, substance abuse, and neurotic, personality, and
      nonpsychotic mental disorders. CONCLUSION: Our study found that rates of relapse
      and time to relapse with aripiprazole were comparable to other SGAs during a 6
      month period. Thus, aripiprazole appears to be an appropriate first-line agent
      along with the other SGAs.

PMID- 17194274
TI  - Attitudes of psychiatrists toward antipsychotic depot medication.
AB  - BACKGROUND: Since 2002, a second-generation depot antipsychotic has been
      available that potentially combines the advantages of depot administration and
      the favorable aspects of the so-called "atypical" antipsychotics. Nevertheless,
      long-acting injectable formulations are seldom prescribed in the treatment of
      schizophrenia. METHOD: We surveyed 350 psychiatrists at an international
      conference as to their reasons for not prescribing a first- or second-generation
      depot antipsychotic for their patients diagnosed with schizophrenia or
      schizoaffective disorder. RESULTS: The most important factor opposing depot
      prescription pertaining to both classes is a presumed sufficient compliance with
      oral antipsychotic treatment. First-generation depots are avoided due to the
      threat of extrapyramidal side effects, whereas second-generation long-acting
      injectable drugs are considered to be associated with high treatment costs. Less
      than 36% of participants' patients have ever been offered antipsychotic depot
      treatment. CONCLUSION: Aversions to prescribing depot treatment are frequent
      among psychiatrists and appear to be unrelated to the antipsychotic class. The
      stated reasons for not prescribing depots are generally not supported by the
      current evidence, and further studies are urgently needed to clarify the
      advantages of depot treatment.

PMID- 17194275
TI  - Omega-3 fatty acids: evidence basis for treatment and future research in
      psychiatry.
AB  - OBJECTIVE: To determine if the available data support the use of omega-3
      essential fatty acids (EFA) for clinical use in the prevention and/or treatment
      of psychiatric disorders. PARTICIPANTS: The authors of this article were invited
      participants in the Omega-3 Fatty Acids Subcommittee, assembled by the Committee
      on Research on Psychiatric Treatments of the American Psychiatric Association
      (APA). EVIDENCE: Published literature and data presented at scientific meetings
      were reviewed. Specific disorders reviewed included major depressive disorder,
      bipolar disorder, schizophrenia, dementia, borderline personality disorder and
      impulsivity, and attention-deficit/hyperactivity disorder. Meta-analyses were
      conducted in major depressive and bipolar disorders and schizophrenia, as
      sufficient data were available to conduct such analyses in these areas of
      interest. CONSENSUS PROCESS: The subcommittee prepared the manuscript, which was
      reviewed and approved by the following APA committees: the Committee on Research
      on Psychiatric Treatments, the Council on Research, and the Joint Reference
      Committee. CONCLUSIONS: The preponderance of epidemiologic and tissue
      compositional studies supports a protective effect of omega-3 EFA intake,
      particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mood
      disorders. Meta-analyses of randomized controlled trials demonstrate a
      statistically significant benefit in unipolar and bipolar depression (p = .02).
      The results were highly heterogeneous, indicating that it is important to examine
      the characteristics of each individual study to note the differences in design
      and execution. There is less evidence of benefit in schizophrenia. EPA and DHA
      appear to have negligible risks and some potential benefit in major depressive
      disorder and bipolar disorder, but results remain inconclusive in most areas of
      interest in psychiatry. Treatment recommendations and directions for future
      research are described. Health benefits of omega-3 EFA may be especially
      important in patients with psychiatric disorders, due to high prevalence rates of
      smoking and obesity and the metabolic side effects of some psychotropic
      medications.

PMID- 17194276
TI  - A double-blind study of citalopram versus placebo in the treatment of compulsive
      sexual behaviors in gay and bisexual men.
AB  - OBJECTIVE: Compulsive sexual behavior (CSB) is a condition characterized by loss
      of control over sexual behavior and repeated negative consequences, including
      unsafe sex. Selective serotonin reuptake inhibitors have been found to reduce CSB
      symptomatology in open-label trials. The objective of this study was to conduct a
      preliminary double-blind, placebo-controlled evaluation of the efficacy,
      acceptability, and tolerability of citalopram in the treatment of CSB. METHOD:
      Twenty-eight men who have sex with men who met the threshold for CSB on the basis
      of existing validated measures participated in a 12-week, double-blind trial of
      citalopram 20 to 60 mg/day to evaluate its effects on CSB symptoms. The primary
      efficacy measure was the Yale-Brown Obsessive Compulsive Scale-Compulsive Sexual
      Behavior. The study was conducted from June 2002 to April 2004. RESULTS:
      Significant treatment effects were obtained for sexual desire/drive (p < .05) and
      frequency of masturbation (p < .01) and pornography use (p < .05). Both groups
      reduced sexual risk, but did not differ significantly. CONCLUSIONS: This study
      provides partial support for the effectiveness of citalopram for reducing
      symptoms of CSB in this population. Larger-scale trials are recommended to
      determine the public health benefits of this treatment.

PMID- 17194277
TI  - Obesity, dyslipidemia, and diabetes with selective serotonin reuptake inhibitors:
      the Hordaland Health Study.
AB  - OBJECTIVE: This study aimed to examine whether subjects taking selective
      serotonin reuptake inhibitors (SSRIs) are more likely to have elements of the
      metabolic syndrome compared with those taking no psychotropic drugs. For
      comparison, we also studied subjects taking antipsychotic drugs. METHOD: We used
      data from The Hordaland Health Study '97-'99, a general community cross-sectional
      health survey including 25,315 subjects aged 40 to 49 and 70 to 74 years. For the
      groups studied, we estimated prevalence and odds ratios (ORs) for obesity,
      hypercholesterolemia, low high-density lipoprotein cholesterol, hyper
      triglyceridemia, and diabetes. RESULTS: We observed an association between use of
      SSRIs as a group (N = 461) and abdominal obesity (OR = 1.40, 95% CI = 1.08 to
      1.81) and hypercholesterolemia (OR = 1.36, 95% CI = 1.07 to 1.73) after adjusting
      for multiple possible confounders. There was also a trend toward an association
      between SSRI use and diabetes. In a subgroup analysis of subjects taking SSRIs,
      the use of paroxetine (N = 187) was markedly associated with both general and
      abdominal obesity but not with hypercholesterolemia. In contrast, the use of
      citalopram (N = 142) was not associated with any of the metabolic outcome
      variables, while the use of any other SSRI (sertraline, fluoxetine, or
      fluvoxamine) (N = 131) as a mixed subgroup was associated with both abdominal
      obesity and hypercholesterolemia. We also replicated the previously reported
      associations between use of antipsychotics and obesity and metabolic
      disturbances. CONCLUSION: We have shown that use of at least some SSRIs is
      associated with clinical and biochemical elements of the metabolic syndrome. Our
      data indicate differences in the metabolic side effect profile among various SSRI
      drugs, although treatment bias might have influenced these results. We suggest
      that patients taking SSRIs be carefully monitored for obesity and dyslipidemia.

PMID- 17194279
TI  - A review of the non-Alzheimer dementias.
AB  - OBJECTIVE: To review the clinical features, neuropathologic features, clinical
      course, differential diagnosis, evaluation, and management strategies of the
      primary non-Alzheimer degenerative and prion disorders that cause dementia. DATA
      SOURCES: The PubMed MEDLINE search engine was used to query for all published
      articles written in English from January 1990 to August 2005 using the keywords
      non-Alzheimer, tau, tauopathy, synuclein, synucleinopathy, prion, cognitive
      impairment, and dementia syndrome. These and related terms were queried on the
      following additional search engines: On-Line Mendelian Inheritance in Man and
      GeneTests. Reputable organizations whose aims include promoting education and
      research in specific syndromes and disorders were queried using the search engine
      Google. STUDY SELECTION: The original articles on the disorders and syndromes,
      and subsequent articles and consensus papers that discussed in detail the
      clinical features, pathologic features, differential diagnosis, evaluation,
      management strategies, or some combination thereof, were selected for this
      review. DATA EXTRACTION: Data were extracted from articles that include generally
      accepted concepts and guidelines on the non-Alzheimer degenerative and prion
      disorders as viewed by the author. DATA SYNTHESIS: The following data were
      synthesized and emphasized: the cardinal clinical features, differential
      diagnosis, findings on ancillary studies most helpful in establishing accurate
      diagnoses, diagnostic criteria, and key principles of management. CONCLUSIONS:
      This article provides an up-to-date overview of the primary non-Alzheimer
      disorders that cause cognitive impairment/dementia to aid the clinician in
      establishing diagnoses and deciding on appropriate management.

PMID- 17194280
TI  - New paradigms in the treatment of Alzheimer's disease.

PMID- 17194281
TI  - ADHD: applying practice guidelines to improve patient outcome and executive
      function.

PMID- 17194282
TI  - Primary care pitfalls for the psychiatrist psychopharmacologist.

PMID- 17194283
TI  - A psychiatrist's diary: contagion.

PMID- 17194285
TI  - Response to the management of autism and its related disorders.

PMID- 17194288
TI  - Methadone hydrochloride to prevent impulsive behavior in mental retardation: a
      case report.

PMID- 17194289
TI  - Onset of unipolar depression or bipolar disorder prior or close to menarche.

PMID- 17194290
TI  - Intimate partner violence, suicidal intent, and alcoholism.

PMID- 17194291
TI  - Agitated depression, panic anxiety, and clonazepam.

PMID- 17194300
TI  - Preschool children's health and its association with parental education and
      individual living conditions in East and West Germany.
AB  - BACKGROUND: Social inequalities in health exist globally and are a major public
      health concern. This study focus on a systematic investigation into the
      associations between health indicators, living conditions and parental
      educational level as indicator of the social status of 6-year-old children living
      in West and East Germany in the decade after re-unification. Explanations of
      observed associations between parental education and health indicators were
      examined. METHODS: All boys and girls entering elementary school and living in
      predefined areas of East and West Germany were invited to participate in a series
      of cross-sectional surveys conducted between 1991 and 2000. Data of 28,888 German
      children with information on parental education were included in the analysis.
      Information about educational level of the parents, individual living conditions,
      symptoms and diagnoses of infectious diseases and allergies were taken from
      questionnaire. At the day of investigation, atopic eczema was diagnosed by
      dermatologists, blood was taken for the determination of allergen-specific immuno
      globulin E, height and weight was measured and lung function tests were done in
      subgroups. Regression analysis was applied to investigate the associations
      between the health indicators and parental educational level as well as the
      child's living conditions. Gender, urban/rural residency and year of survey were
      used to control for confounding. RESULTS: Average response was 83% in East
      Germany and 71% in West Germany. Strong associations between health indicators
      and parental education were observed. Higher educated parents reported more
      diagnoses and symptoms than less educated. Children of higher educated parents
      were also more often sensitized against grass pollen or house dust mites, but had
      higher birth weights, lower airway resistance and were less overweight at the age
      of six. Furthermore, most of the health indicators were significantly associated
      with one or more living conditions such as living as a single child, unfavourable
      indoor air, damp housing condition, maternal smoking during pregnancy or living
      near a busy road. The total lung capacity and the prevalence of an atopic eczema
      at the day of investigation were the only health indicators those did not show
      associations with any of the predictor variables. CONCLUSION: Despite large
      differences in living conditions and evidence that some poor health outcomes were
      directly associated with poor living conditions, only few indicators demonstrated
      poorer health in social disadvantaged children. These were in both parts of
      Germany increased levels of overweight, higher airway resistance and, in East
      Germany only, reduced height in children with lower educated parents compared to
      those of higher education. In both East and West Germany, higher prevalence of
      airway symptoms was associated with a damp housing condition, and lower birth
      weight, reduced height and increased airway resistance at the age of six were
      associated with maternal smoking during pregnancy. The latter explained to a
      large extent the difference in birth weight and airway resistance between the
      educational groups.

PMID- 17194301
TI  - Acute scrotum as a complication of Thiersch operation for rectal prolapse in a
      child.
AB  - BACKGROUND: We report a case of acute scrotal condition that presented in a four
      year old male child one year after being treated for an idiopathic rectal
      prolapse utilizing Thiersch wire. CASE PRESENTATION: The acute scrotum had
      resulted from spreading perianal infection due to erosion of the circlage wire.
      The condition was treated with antibiotics and removal of the wire. The child
      made an uneventful recovery. CONCLUSION: This case highlights that patients with
      Thiersch wire should be followed until the wire is removed. Awareness of anal
      lesions as a cause of acute scrotal conditions, and history and physical
      examination are emphasized.

PMID- 17194302
TI  - The molecular epidemiology of Stenotrophomonas maltophilia bacteraemia in a
      tertiary referral hospital in the United Arab Emirates 2000-2004.
AB  - BACKGROUND: Stenotrophomonas maltophilia is recognised as an important cause of
      nosocomial infection, especially in immunocompromised patients, resulting in
      significant morbidity and mortality. The treatment of S. maltophilia infection
      presents a therapeutic challenge. The precise modes of transmission of S.
      maltophilia in the hospital environment are not known and such knowledge is
      essential to target interventions to prevent spread. There are few published data
      on the patterns of nosocomial infection in the United Arab Emirates (UAE). A
      recent study showed that S. maltophilia is an established cause of bloodstream
      infection in Tawam Hospital in the UAE. Little is known about its epidemiology in
      the hospital. METHODS: We describe the clinical characteristics of 25 episodes of
      S. maltophilia bacteraemia which occurred from 2000-2004. The strains were
      characterised using pulsed field gel electrophoresis (PFGE). RESULTS: All
      episodes were hospital-acquired and malignancy and central venous catheters were
      predisposing factors. Catheter-associated infection comprised 88% infection.
      Catheter removal was important for the successful management of catheter
      associated infection. The results of PFGE suggested that there were as many
      strains as patients. S. maltophilia strains isolated from the same patient had
      indistinguishable PFGE profiles. CONCLUSION: PFGE is a valid and reproducible
      typing method for S. maltophilia. The precise sources and modes of spread of S.
      maltophilia in the hospital are still not known. Knowledge that person to person
      transmission was not a major mode of transmission enabled infection control
      interventions for S. maltophilia to be targeted more effectively.

PMID- 17194303
TI  - Libya, HIV, and open communication.
AB  - This year-end editorial discusses several points including the recent Libyan
      verdict sentencing five Bulgarian nurses and a Palestinian doctor to death for
      allegedly infecting 426 children with HIV. It also comments on the role played by
      open communication for bridging cultural misunderstandings and summarizes briefly
      Retrovirology's progress in 2006.

PMID- 17194305
TI  - Public health preparedness in Alberta: a systems-level study.
AB  - BACKGROUND: Recent international and national events have brought critical
      attention to the Canadian public health system and how prepared the system is to
      respond to various types of contemporary public health threats. This article
      describes the study design and methods being used to conduct a systems-level
      analysis of public health preparedness in the province of Alberta, Canada. The
      project is being funded under the Health Research Fund, Alberta Heritage
      Foundation for Medical Research. METHODS/DESIGN: We use an embedded, multiple
      case study design, integrating qualitative and quantitative methods to measure
      empirically the degree of inter-organizational coordination existing among public
      health agencies in Alberta, Canada. We situate our measures of inter
      organizational network ties within a systems-level framework to assess the
      relative influence of inter-organizational ties, individual organizational
      attributes, and institutional environmental features on public health
      preparedness. The relative contribution of each component is examined for two
      potential public health threats: pandemic influenza and West Nile virus.
      DISCUSSION: The organizational dimensions of public health preparedness depend on
      a complex mix of individual organizational characteristics, inter-agency
      relationships, and institutional environmental factors. Our study is designed to
      discriminate among these different system components and assess the independent
      influence of each on the other, as well as the overall level of public health
      preparedness in Alberta. While all agree that competent organizations and
      functioning networks are important components of public health preparedness, this
      study is one of the first to use formal network analysis to study the role of
      inter-agency networks in the development of prepared public health systems.

PMID- 17194304
TI  - Comprehensive analysis of alternative splicing in rice and comparative analyses
      with Arabidopsis.
AB  - BACKGROUND: Recently, genomic sequencing efforts were finished for Oryza sativa
      (cultivated rice) and Arabidopsis thaliana (Arabidopsis). Additionally, these two
      plant species have extensive cDNA and expressed sequence tag (EST) libraries. We
      employed the Program to Assemble Spliced Alignments (PASA) to identify and
      analyze alternatively spliced isoforms in both species. RESULTS: A comprehensive
      analysis of alternative splicing was performed in rice that started with >1.1
      million publicly available spliced ESTs and over 30,000 full length cDNAs in
      conjunction with the newly enhanced PASA software. A parallel analysis was
      performed with Arabidopsis to compare and ascertain potential differences between
      monocots and dicots. Alternative splicing is a widespread phenomenon (observed in
      greater than 30% of the loci with transcript support) and we have described nine
      alternative splicing variations. While alternative splicing has the potential to
      create many RNA isoforms from a single locus, the majority of loci generate only
      two or three isoforms and transcript support indicates that these isoforms are
      generally not rare events. For the alternate donor (AD) and acceptor (AA)
      classes, the distance between the splice sites for the majority of events was
      found to be less than 50 basepairs (bp). In both species, the most frequent
      distance between AA is 3 bp, consistent with reports in mammalian systems.
      Conversely, the most frequent distance between AD is 4 bp in both plant species,
      as previously observed in mouse. Most alternative splicing variations are
      localized to the protein coding sequence and are predicted to significantly alter
      the coding sequence. CONCLUSION: Alternative splicing is widespread in both rice
      and Arabidopsis and these species share many common features. Interestingly,
      alternative splicing may play a role beyond creating novel combinations of
      transcripts that expand the proteome. Many isoforms will presumably have negative
      consequences for protein structure and function, suggesting that their biological
      role involves post-transcriptional regulation of gene expression.

PMID- 17194307
TI  - Developing global climate anomalies suggest potential disease risks for 2006
      2007.
AB  - BACKGROUND: El Nino/Southern Oscillation (ENSO) related climate anomalies have
      been shown to have an impact on infectious disease outbreaks. The Climate
      Prediction Center of the National Oceanic and Atmospheric Administration
      (NOAA/CPC) has recently issued an unscheduled El Nino advisory, indicating that
      warmer than normal sea surface temperatures across the equatorial eastern Pacific
      may have pronounced impacts on global tropical precipitation patterns extending
      into the northern hemisphere particularly over North America. Building evidence
      of the links between ENSO driven climate anomalies and infectious diseases,
      particularly those transmitted by insects, can allow us to provide improved long
      range forecasts of an epidemic or epizootic. We describe developing climate
      anomalies that suggest potential disease risks using satellite generated data.
      RESULTS: Sea surface temperatures (SSTs) in the equatorial east Pacific ocean
      have anomalously increased significantly during July - October 2006 indicating
      the typical development of El Nino conditions. The persistence of these
      conditions will lead to extremes in global-scale climate anomalies as has been
      observed during similar conditions in the past. Positive Outgoing Longwave
      Radiation (OLR) anomalies, indicative of severe drought conditions, have been
      observed across all of Indonesia, Malaysia and most of the Philippines, which are
      usually the first areas to experience ENSO-related impacts. This dryness can be
      expected to continue, on average, for the remainder of 2006 continuing into the
      early part of 2007. During the period November 2006 - January 2007 climate
      forecasts indicate that there is a high probability for above normal rainfall in
      the central and eastern equatorial Pacific Islands, the Korean Peninsula, the
      U.S. Gulf Coast and Florida, northern South America and equatorial east Africa.
      Taking into consideration current observations and climate forecast information,
      indications are that the following regions are at increased risk for disease
      outbreaks: Indonesia, Malaysia, Thailand and most of the southeast Asia Islands
      for increased dengue fever transmission and increased respiratory illness;
      Coastal Peru, Ecuador, Venezuela, and Colombia for increased risk of malaria;
      Bangladesh and coastal India for elevated risk of cholera; East Africa for
      increased risk of a Rift Valley fever outbreak and elevated malaria; southwest
      USA for increased risk for hantavirus pulmonary syndrome and plague; southern
      California for increased West Nile virus transmission; and northeast Brazil for
      increased dengue fever and respiratory illness. CONCLUSION: The current
      development of El Nino conditions has significant implications for global public
      health. Extremes in climate events with above normal rainfall and flooding in
      some regions and extended drought periods in other regions will occur.
      Forecasting disease is critical for timely and efficient planning of operational
      control programs. In this paper we describe developing global climate anomalies
      that suggest potential disease risks that will give decision makers additional
      tools to make rational judgments concerning implementation of disease prevention
      and mitigation strategies.

PMID- 17194306
TI  - Human coronavirus 229E encodes a single ORF4 protein between the spike and the
      envelope genes.
AB  - BACKGROUND: The genome of coronaviruses contains structural and non-structural
      genes, including several so-called accessory genes. All group 1b coronaviruses
      encode a single accessory protein between the spike and envelope genes, except
      for human coronavirus (HCoV) 229E. The prototype virus has a split gene, encoding
      the putative ORF4a and ORF4b proteins. To determine whether primary HCoV-229E
      isolates exhibit this unusual genome organization, we analyzed the ORF4a/b region
      of five current clinical isolates from The Netherlands and three early isolates
      collected at the Common Cold Unit (CCU) in Salisbury, UK. RESULTS: All Dutch
      isolates were identical in the ORF4a/b region at amino acid level. All CCU
      isolates are only 98% identical to the Dutch isolates at the nucleotide level,
      but more closely related to the prototype HCoV-229E (>98%). Remarkably, our
      analyses revealed that the laboratory adapted, prototype HCoV-229E has a 2
      nucleotide deletion in the ORF4a/b region, whereas all clinical isolates carry a
      single ORF, 660 nt in size, encoding a single protein of 219 amino acids, which
      is a homologue of the ORF3 proteins encoded by HCoV-NL63 and PEDV. CONCLUSION:
      Thus, the genome organization of the group 1b coronaviruses HCoV-NL63, PEDV and
      HCoV-229E is identical. It is possible that extensive culturing of the HCoV-229E
      laboratory strain resulted in truncation of ORF4. This may indicate that the
      protein is not essential in cell culture, but the highly conserved amino acid
      sequence of the ORF4 protein among clinical isolates suggests that the protein
      plays an important role in vivo.

PMID- 17194308
TI  - Detection of transcriptional difference of porcine imprinted genes using
      different microarray platforms.
AB  - BACKGROUND: Presently, multiple options exist for conducting gene expression
      profiling studies in swine. In order to determine the performance of some of the
      existing microarrays, Affymetrix Porcine, Affymetrix Human U133+2.0, and the U.S.
      Pig Genome Coordination Program spotted glass oligonucleotide microarrays were
      compared for their reproducibility, coverage, platform independent and dependent
      sensitivity using fibroblast cell lines derived from control and parthenogenic
      porcine embryos. RESULTS: Array group correlations between technical replicates
      demonstrated comparable reproducibility in both Affymetrix arrays. Glass
      oligonucleotide arrays showed greater variability and, in addition, approximately
      10% of probes had to be discarded due to slide printing defects. Probe level
      analysis of Affymetrix Human arrays revealed significant variability within probe
      sets due to the effects of cross-species hybridization. Affymetrix Porcine arrays
      identified the greatest number of differentially expressed genes amongst probes
      common to all arrays, a measure of platform sensitivity. Affymetrix Porcine
      arrays also identified the greatest number of differentially expressed known
      imprinted genes using all probes on each array, an ad hoc measure of realistic
      performance for this particular experiment. CONCLUSION: We conclude that of the
      platforms currently available and tested, the Affymetrix Porcine array is the
      most sensitive and reproducible microarray for swine genomic studies.

PMID- 17194309
TI  - Health indicators and human development in the Arab region.
AB  - BACKGROUND: The present paper deals with the relationship between health
      indicators and human development in the Arab region. Beyond descriptive analysis
      showing geographic similarities and disparities inter countries, the main purpose
      is to point out health deficiencies and to propose pragmatic strategies
      susceptible to improve health conditions and consequently enhance human
      development in the Arab world. METHODS: Data analysis using Principal Components
      Analysis is used to compare the achievements of the Arab countries in terms of
      direct and indirect health indicators. The variables (indicators) are seen to be
      well represented on the circle of correlation, allowing for interesting
      interpretation and analysis. The 19 countries are projected on the first and
      second plane respectively. RESULTS: The results given by the present analysis
      give a good panorama of the Arab countries with their geographic similarities and
      disparities. The high correlation between health indicators and human development
      is well illustrated and consequently, countries are classified by groups having
      similar human development. The analysis shows clearly how health deficits are
      impeding human development in the majority of Arab countries and allows us to
      formulate suggestions to improve health conditions and enhance human development
      in the Arab World. DISCUSSION: The discussion is based on the link between
      different direct and indirect health indicators and the relationship between
      these indicators and human development index. Without including the GDP
      indicator, our analysis has shown that the 19 Arab countries may be classified,
      independently of their geographic proximity, in three different groups according
      to their global human development level (Low, Medium and High). Consequently,
      while identifying health deficiencies in each group, the focus was made on the
      countries presenting a high potential of improvement in health indicators. In
      particular, maternal mortality and infant mortality which are really challenging
      health authorities of the first and third group were critically discussed.
      CONCLUSION: The Arab countries have made substantial economic and social progress
      during the last decades by improving life expectancy and reducing maternal and
      infant mortality. However, considering its natural wealth and human resources,
      the Arab region has accomplished less than expected in terms of human
      development. Huge social inequalities and health inequities exist inter and intra
      Arab countries. In most Arab countries, a large percentage of populations,
      especially in rural areas, are deprived of access to health facilities.
      Consequently, many women still die during pregnancy and labour, yielding
      unacceptable levels of maternal and infant mortality. However, the problem is
      seen to be more complex, going beyond geography and technical accessibility to
      health care, it compasses, among others, levels of literacy, low social and
      economic status of women, qualification of health staff, general behaviour and
      interactions between patients and medical personnel (including corruption).

PMID- 17194310
TI  - Case report: infective endocarditis caused by Brevundimonas vesicularis.
AB  - BACKGROUND: There are few reports in the literature of invasive infection caused
      by Brevundimonas vesicularis in patients without immunosuppression or other
      predisposing factors. The choice of antimicrobial therapy for bacteremia caused
      by the pathogen requires more case experience to be determined. CASE
      PRESENTATION: The case of a 40-year-old previously healthy man with subacute
      endocarditis proposed to be contributed from an occult dental abscess is
      described. The infection was found to be caused by B. vesicularis on blood
      culture results. The patient recovered without sequelae after treatment with
      ceftriaxone followed by subsequent ciprofloxacin therapy owing to an allergic
      reaction to ceftriaxone and treatment failure with ampicillin/sulbactam.
      CONCLUSION: To our knowledge, this is the first report of B. vesicularis as a
      cause of infective endocarditis. According to an overview of the literature and
      our experience, we suggest that third-generation cephalosporins,
      piperacillin/tazobactam, and ciprofloxacin are effective in treating invasive B.
      vesicularis infections, while the efficacy of ampicillin-sulbactam needs further
      evaluation.

PMID- 17194311
TI  - Use of taste-masking product, FLAVORx, to assist Thai children to ingest generic
      antiretrovirals.
AB  - We evaluated whether FLAVORx helped thirty Thai children take opened capsule,
      crushed tablets and liquid generic ARVs with more ease. All children had
      excellent adherence, evaluated by PACTG Standard International Questionnaire and
      interviewing, before and after one month of FLAVORx. Eighty percent took ARV with
      more ease and wish to continue FLAVORx. Strawberry was the most popular flavor.

PMID- 17194312
TI  - The mystique of direct laryngoscopy.

PMID- 17194313
TI  - Humidification and noninvasive ventilation.

PMID- 17194314
TI  - Management of tracheal intubation in the respiratory intensive care unit by
      pulmonary physicians.
AB  - BACKGROUND: Expert management of tracheal intubation has become fundamental to
      the routine practice of pulmonary physicians who work in respiratory intensive
      care units (ICUs). In Italy, tracheal intubation is not included as part of the
      training in respiratory medicine, and pulmonary physicians are usually dissuaded
      from managing intubations. METHODS: We prospectively studied the intubation
      success rate in 46 consecutive respiratory ICU patients who required either
      emergency or urgent intubation, conducted by 3 intubation-trained pulmonary
      physicians in our respiratory ICU. Intubation success was defined as successful
      tracheal intubation without any of 7 pre-defined complications. RESULTS: There
      were 17 emergency intubations and 29 urgent intubations. Intubation was
      successful in 43 of the 46 intubation attempts. Complications occurred in 3
      cases: 2 patients needed to be intubated by an anesthesiologist, and 1 patient
      received fiberoptic intubation. CONCLUSIONS: Pulmonary physicians trained in
      tracheal intubation can have a high success rate in performing intubation in the
      respiratory ICU. Collaborative efforts between anesthesiologists and pulmonary
      physicians are necessary to optimize the training, skill-retention, and back-up
      for advanced airway management in the respiratory ICU.

PMID- 17194315
TI  - Time course of physiologic variables in response to ventilator-induced lung
      injury.
AB  - BACKGROUND: The time course of the physiological derangements that result from
      ventilator-induced lung injury has not been adequately described. Similarly, the
      regional topographies of pleural pressure and tissue edema have not been
      carefully mapped for this injury process. METHODS: Lung injury was induced in 9
      normal pigs by ventilating for 6 hours at a transpulmonary pressure of 35 cm
      H(2)O, with the animals in the supine position. Eight additional normal pigs
      received right thoracotomy to place pleural-surface-pressure sensors prior to an
      identical period and intensity of injurious ventilation. Gas exchange and lung
      mechanics were tracked in all the animals. Cytokines (tumor necrosis factor
      alpha, interleukin 6, and interleukin 8) in peripheral blood were assayed at 2
      hour intervals, beginning at the onset of mechanical ventilation, from all the
      animals. RESULTS: After a brief "induction" period, P(aO(2)) and tidal volume
      declined steadily in the animals that were ventilated to induce lung injury. The
      rate of decline was greater in the animals that received thoracotomy. The pleural
      pressure gradient steadily increased from ventral to dorsal. The serum cytokine
      levels did not evolve with developing injury, but cytokines were elevated at the
      onset of ventilation. Tissue edema, as assessed by the ratio of wet weight to dry
      weight, was greater in the thoracotomized animals than in the nonthoracotomized
      animals, and tissue edema tended to be greater in the caudal lung regions than in
      the cephalad lung regions. CONCLUSIONS: Following the induction period, the
      development of ventilator-induced lung injury progressed steadily and then
      plateaued, as assessed by quantitative physiology variables during 6 hours of
      ventilation at a transpulmonary pressure of 35 cm H(2)O. Greater injury developed
      in animals that had a coexisting potential insult (thoracotomy). Injury
      development was not paralleled by bloodborne inflammatory cytokines.

PMID- 17194316
TI  - Efficacy of a heated passover humidifier during noninvasive ventilation: a bench
      study.
AB  - BACKGROUND: Noninvasive positive-pressure ventilation (NPPV) delivers air at a
      high flow, which is associated with airway mucosal drying and impaired airway
      functioning. OBJECTIVES: To examine the effects of mechanical ventilation
      parameters on relative humidity and absolute humidity during NPPV, and to
      evaluate the effect of a heated passover humidifier on relative humidity,
      absolute humidity, and ventilator performance during NPPV. METHODS: We performed
      a bench study to assess the effects of inspiratory positive airway pressure
      (IPAP) of 10 cm H(2)O, 15 cm H(2)O, and 20 cm H(2)O, respiratory rates of 12
      breaths/min and 24 breaths/min, and inspiratory-expiratory ratios of 1:2 and 1:3
      on relative and absolute humidity. The measurements were obtained on room air and
      with a heated humidifier at medium and maximum heater settings. RESULTS: Without
      humidification, the relative humidity in the NPPV circuit (range 16.3-26.5%) was
      substantially lower than the ambient relative humidity (27.6-31.5%) at all
      ventilatory settings. Increasing the IPAP decreased the relative humidity
      (Spearman's rho = 0.67, p < 0.001). Changing the respiratory rate or inspiratory
      expiratory ratio had no significant effect. Both relative and absolute humidity
      increased with humidification, and the air was fully saturated at the maximum
      heater setting. Delivered IPAP was reduced by 0.5-1 cm H(2)O during
      humidification. CONCLUSIONS: NPPV delivers air with a low relative humidity,
      especially with high inspiratory pressure. Addition of a heated humidifier
      increases the relative and absolute humidity to levels acceptable for
      nonintubated patients, with minimal effect on delivered pressure. Consideration
      should be given to heated humidification during NPPV, especially when airway
      drying and secretion retention are of concern.

PMID- 17194317
TI  - Measurement of pulsatile tidal volume, pressure amplitude, and gas flow during
      high-frequency percussive ventilation, with and without partial cuff deflation.
AB  - OBJECTIVE: With a high-frequency percussive ventilator and a mechanical lung
      model, to measure tidal volume (V(T)), pulsatile pressure amplitude (difference
      between peak and nadir pulsatile pressure [DeltaP];), and mean airway pressure (P
      (aw)) at various pulsatile frequencies, pulsatile inspiratory-expiratory ratios
      (I:E(p)), and pressures (measured at the interface between the pulse-generator
      and the endotracheal tube [P(vent)]). METHODS: With the endotracheal tube inside
      an artificial trachea, we manipulated the high-frequency percussive ventilation
      settings and adjuncts, including pulsatile frequency, I:E(p), and P(vent) by
      manipulating pulsatile flow. We also studied the effects of partially deflating
      the endotracheal tube cuff. We measured P (aw), pulsatile pressure amplitude at
      the carina (DeltaP(c)), and pulsatile V(T) at the carina. With the cuff partly
      deflated, we measured the fraction of inspired oxygen (F(IO(2))) in the gas
      efflux above and below the cuff. RESULTS: Increasing the pulsatile frequency from
      300 cycles/min to 600 cycles/min and changing the I:E(p) from 1:3 to 1:1
      significantly reduced V(T) (p < 0.001). P (aw) and DeltaP(c) were unaffected by
      the change in pulsatile frequency or I:E(p), except when we did not preserve the
      pulsatile flow. The measured V(T) range was from 19.1 mL (at 600 cycles/min) to
      47.3 mL (at 300 cycles/min). Partial cuff deflation did not significantly reduce
      P (aw) or DeltaP(c), but it did significantly reduce V(T) and F(IO(2)).
      CONCLUSION: During high-frequency percussive ventilation, the pulsatile frequency
      is inversely related to V(T). Partial cuff deflation reduces the delivered
      F(IO(2)).

PMID- 17194318
TI  - Setting positive end-expiratory pressure during jet ventilation to replicate the
      mean airway pressure of oscillatory ventilation.
AB  - BACKGROUND: High-frequency ventilation can be delivered with either oscillatory
      ventilation (HFOV) or jet ventilation (HFJV). Traditional clinician biases may
      limit the range of function of these important ventilation modes. We hypothesized
      that (1) the jet ventilator can be an accurate monitor of mean airway pressure (P
      (aw)) during HFOV, and (2) a mathematical relationship can be used to determine
      the positive end-expiratory pressure (PEEP) setting required for HFJV to
      reproduce the P (aw) of HFOV. METHODS: In phase 1 of our experiment, we used a
      differential pressure pneumotachometer and a jet adapter in-line between an
      oscillator circuit and a pediatric lung model to measure P (aw), PEEP, and peak
      inspiratory pressure (PIP). Thirty-six HFOV setting combinations were studied, in
      random order. We analyzed the correlation between the pneumotachometer and HFJV
      measurements. In phase 2 we used the jet as the monitoring device during each of
      the same 36 combinations of HFOV settings, and recorded P (aw), PIP, and DeltaP.
      Then, for each combination of settings, the jet ventilator was placed in-line
      with a conventional ventilator and was set at the same rate and PIP as was
      monitored during HFOV. To determine the appropriate PEEP setting, we calculated
      the P (aw) contributed by the PIP, respiratory rate, and inspiratory time set for
      HFJV, and subtracted this from the goal P (aw). This value was the PEEP predicted
      for HFJV to match the HFOV P (aw). RESULTS: The correlation coefficient between
      the pneumotachometer and HFJV measurements was r = 0.99 (mean difference 0.62 +/-
      0.30 cm H(2)O, p < 0.001). The predicted and actual PEEP required were highly
      correlated (r = 0.99, p < 0.001). The mean difference in these values is not
      statistically significantly different from zero (mean difference 0.25 +/- 1.02 cm
      H(2)O, p > 0.15). CONCLUSIONS: HFJV is an accurate monitor during HFOV. These
      measurements can be used to calculate the predicted PEEP necessary to match P
      (aw) on the 2 ventilators. Replicating the P (aw) with adequate PEEP on HFJV may
      help simplify transitioning between ventilators when clinically indicated.

PMID- 17194319
TI  - The mixed venous oxygen saturation response to weaning from mechanical
      ventilation.

PMID- 17194320
TI  - [Definitions of neonatal sepsis: a long way to go].

PMID- 17194321
TI  - [Neonatal neoplasms: a single-centre experience].
AB  - INTRODUCTION: Malignant tumors are uncommon in the neonatal period and benign
      tumors may have malignant potential. OBJECTIVES: To describe the neoplasms
      diagnosed and treated in newborns (</= 28 days of life) in the Hospital
      Universitario de Canarias and their association with congenital abnormalities and
      to evaluate prenatal diagnosis of these tumors. PATIENTS AND METHODS: The medical
      records of patients with neoplasms diagnosed during the neonatal period in the
      previous 25 years in our hospital were retrospectively reviewed. The variables
      analyzed were the percentage of neonatal neoplasms among the total number of
      cancer cases in children aged less than 14 years, their incidence among all the
      newborns in our hospital, sex, year of diagnosis, age at clinical diagnosis, the
      presence or absence of prenatal diagnosis, type of tumor (histologic diagnosis),
      association with syndromes or other congenital anomalies, treatment, and long
      term outcome. RESULTS: Of 260 neoplasms diagnosed in our unit from 1980, 16 (6.1
      %) were diagnosed in the neonatal period. The incidence of neonatal neoplasms was
      estimated to be 276.5 per million live births. Males accounted for 43.8 % and
      females for 56.2 %, with a mean age at diagnosis of 5.5 days (range 1-28 days).
      Five neonates (31.2 %) had a prenatal diagnosis, 60 % of which were made in the
      last 7 years of the study period. A further five newborns were diagnosed at the
      initial neonatal examination. Histologic diagnoses were neuroblastoma (n = 5;
      31.2 %), teratoma/ germ cell tumor (n = 4; 25 %), soft tissue sarcoma (one
      fibrosarcoma of the thigh and two hemangiopericytoma of the back and heart; 18.8
      %), and one case each of mesoblastic nephroma, cerebral tumor (ependymoblastoma),
      melanoma (associated with giant congenital melanocytic nevi), and acute leukemia
      (associated with Down syndrome). Treatment consisted of surgery alone (n = 10;
      62.5 %) and surgery plus chemotherapy (n = 5; 31.2 %); one patient received no
      treatment. The overall actuarial survival rate was 87.5 %. Sequelae were observed
      in 33.3 % of survivors. CONCLUSIONS: The neoplasms most frequently diagnosed in
      the neonatal period were solid tumors, mainly neuroblastoma and teratomas/germ
      cell tumors; 12.5 % were associated with syndromes or congenital anomalies. In
      the last 7 years, the prenatal diagnosis of these entities has improved. Most of
      the neoplasms responded to therapy, mainly surgery, and long-term outcome was
      favorable.

PMID- 17194322
TI  - [Disparity in the criteria for including patients with neonatal sepsis in
      scientific medical studies. Are we swimming in a sea without limits?].
AB  - OBJECTIVE: To characterize disparity in the criteria used for patient enrollment
      in clinical research on neonatal sepsis. MATERIAL AND METHODS: We used MEDLINE to
      identify clinical research in neonatal sepsis published in English from 1993 to
      2005. We used the criteria of the International Consensus Conference Panel:
      International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and
      Organ Dysfunction in Pediatrics (IPSCC) published in 2005 as an arbitrary
      standard in each of the articles. Articles were considered to define neonatal
      sepsis clearly if they mentioned the criteria and described the values used.
      Articles were considered not to define neonatal sepsis clearly if they used the
      phrase "septic patients were included" without describing the variables or values
      used for inclusion. RESULTS: We identified 150 articles, of which 26.6 %
      specified the criteria and values of the IPSCC. The remaining 110 articles did
      not mention the values or the variables used to define neonatal sepsis.
      CONCLUSION: There is a disparity in the criteria used to operatively define
      neonatal sepsis in clinical studies performed in distinct parts of the world.

PMID- 17194323
TI  - [Characteristics of neonates with and without a single umbilical artery. Analysis
      of two consecutive series of neonates with and without congenital defects].
AB  - BACKGROUND AND OBJECTIVE: The implications of the presence of a single umbilical
      artery (SUA) are unknown. Although most articles are based on selected samples,
      they suggest a relationship between SUA and malformations. Consequently, prenatal
      detection of SUA causes concern, since there are no definitive guidelines that
      can be followed after identification of this abnormality. The objective of this
      study was to comparatively analyze SUA in two series of consecutive births, with
      and without congenital defects. PATIENTS AND METHODS: A total of 19,909 cases and
      19,148 controls from the Registry of the Spanish Collaborative Study on
      Congenital Malformations were studied. The variables analyzed were sex, birth
      weight, length, occipito-frontal circumference, gestational age, prematurity,
      delivery by caesarean section, umbilical cord length, placental weight, survival
      at 72 hours, primiparity, oligohydramnios, and polyhydramnios. Calculations
      included relative frequency, odds ratios (OR) and 95 % confidence intervals, the
      chi-square test, Fisher's p-value, and Student's t-test. RESULTS: SUA was found
      in 2.29 % of cases and in 1.03 % of controls (p = 0.0000001). These figures
      showed secular variation due to improvements in prenatal diagnosis and
      interruption of some pregnancies. When cases with and without SUA were compared,
      those with SUA had lower values of somatometry at birth, umbilical cord length
      and gestational age and had a higher risk for oligohydramnios, polyhydramnios,
      caesarean section, and death in the first 72 hours. Among controls, the only
      differences were a shorter umbilical cord and a higher frequency of
      oligohydramnios among infants with SUA. CONCLUSIONS: The results suggest that
      certain malformations associated with SUA could cause some of the differences
      among cases. Shortening of the umbilical cord and oligohydramnios could be
      related to SUA, as these abnormalities were found in both cases and controls.
      Comparison of cases and controls suggests that the etiopathogenesis of SUA could
      differ in the two groups.

PMID- 17194324
TI  - [Acute toxoplasmosis: clinical and laboratory data in eleven patients].
AB  - INTRODUCTION: The clinical and laboratory data of immunocompetent patients with
      acute toxoplasmosis (AT) are described. PATIENTS AND METHODS: We performed a
      retrospective study of patients with AT attended between 1996 and 2004.
      Diagnostic criteria consisted of compatible clinical findings (generalized and
      cervical lymphadenopathies) and specific serology against Toxoplasma gondii (high
      IgG and IgM and/or reactive IgA). IgG and IgM determinations were performed by
      ELFA and IgA determinations by ELISA. IgM-CMV, heterophil antibodies, hemogram,
      hepatic chemistry were also determined and funduscopic examination was performed.
      RESULTS: Eleven immunocompetent patients with AT were evaluated. The mean age was
      8.8 years (95 % CI: 3.6-12.9). The patients were evaluated between the first and
      the third month after symptom onset. Of the 11 patients, hard elastic
      lymphadenopathies were found in 10, single cervical lymphadenectomy in three and
      generalized lymphadenectomy in seven. One patient showed no symptoms. In one
      patient, nodal histology showed the Piringer-Kuchinka triad. None of the patients
      showed alterations in the hemogram, hepatic chemistry or funduscopic examination.
      The mean IgG value was 4.143 UI/ml (95 % CI: 2.570 and 5.717). IgM was reactive
      in nine of the 11 patients (81.8 %) and IgA in seven out of 10 patients (70 %).
      In all patients, at least one of these two immunoglobulins was reactive. In all
      patients, clinical outcome was favorable without parasiticide treatment.
      CONCLUSION: Except for one asymptomatic patient, all the patients had generalized
      lymphadenopathies and only 27.2 % showed cervical lymphadenopathies. A negative
      IgM or IgA result does not rule out a diagnosis of AT. Parasiticide treatment is
      unnecessary in this entity. Acute toxoplasmosis should be considered early in
      children with lymphadenopathies to avoid invasive procedures.

PMID- 17194325
TI  - [What would happen if day care centers closed?].
AB  - OBJECTIVE: To determine the possible association between the decrease in
      emergency episodes and the strike in day care centers in Vitoria (Spain) in the
      autumn of 2004, which affected 86 % of children attending these centers. PATIENTS
      AND METHOD: We performed a retrospective observational study. In Vitoria, there
      were 27404 children under the age of 14 in 2004; of these, 5890 were under the
      age of 3 years. The day care centers on strike affected 25.4 % of the latter. We
      compared emergency episodes and hospital admissions during the strike (September
      to November, 2004) with those occurring in the previous 5 years. To contrast the
      hypothesis, a comparison of proportions was used with statistical significance
      set at p < 0.005. RESULTS: A significant decrease (rate x 1000 inhabitants) was
      observed in the number of emergency episodes in children under 3 years old in two
      of the three months of the strike (October and November, p < 0.01). No
      significant differences were observed in emergency rates in children aged more
      than 3 years old, or in hospital admissions in all ages. CONCLUSIONS: These data
      suggest that children attending day care centers have a higher risk of catching
      banal diseases (which do not require hospital admission and are probably
      infectocontagious illnesses) than children not attending these centers, thus
      increasing demand for pediatric emergency services. Since the solution does not
      lie in closing day care centers, hygienic and sanitary measures should be
      maximized in these centers.

PMID- 17194326
TI  - [Evaluation of therapeutic strategies in congenital nephrotic syndrome of the
      Finnish type].
AB  - INTRODUCTION: Congenital nephrotic syndrome of the Finnish type (CNFS) is caused
      by mutations in the nephrin gene. This disease manifests as massive proteinuria,
      gross peripheral edema, and ascites during the first weeks of life. In the last
      few years the prognosis has improved due to new treatment strategies:
      antiproteinuria drugs, intensive nutrition, nephrectomy, dialysis, and renal
      transplantation. The aim of this study was to determine the impact of these
      therapeutic measures. PATIENTS AND METHOD: We performed a descriptive
      retrospective epidemiological study of 12 patients diagnosed with CNSF between
      January 1985 and August 2005. We included patients aged less than 14 years old
      with massive proteinuria and generalized edema during the neonatal period, a
      large placenta (> 25 % of birth weight), and normal glomerular filtration rate
      during the first 6 months of life, in whom other causes of congenital nephrotic
      syndrome were ruled out. RESULTS: The diagnosis was established after a median
      period of 17 days (range 6-30). The most commonly used treatments were albumin
      infusions (91.7 %), angiotensin-converting enzyme inhibitors (66.7 %), and
      indomethacin (58.3 %). Dialysis was started in 58.3 %, at a median age of 3.76
      years (2.81-7.6). The main complication was acute peritonitis (85.7 %). Renal
      transplantation was performed in 58.3 % of the patients; of these, 71.4 % have
      normal renal function after a median follow-up of 3.73 years (0.8-6.3). The
      median plasma albumin level during the pretransplant period was 0.17 g/dL (0.12
      0.28). Plasma cholesterol and triglyceride levels decreased significantly after
      renal transplantation (p = 0.043). Fifty percent of the patients achieved
      adequate height and weight for their age and gender. Mortality was 33.3 %.
      CONCLUSION: Antiproteinuria drugs and intensive nutritional therapy improve
      clinical control and delay the start of dialysis and renal transplantation,
      increasing the probability of success.

PMID- 17194327
TI  - [Early postoperative complications of thoracoscopy versus thoracotomy in
      pediatric idiopathic scoliosis].
AB  - INTRODUCTION: Thoracoscopic surgery has been used for anterior release,
      discectomy, and fusion in severe scoliosis or kyphosis. The indications of
      thoracoscopy for the treatment of pediatric spinal deformity are similar to those
      of thoracotomy-based spinal surgery. OBJECTIVE: We designed a comparative study
      to observe the immediate complications in the postoperative period after
      thoracoscopy or thoracotomy for scoliosis in the pediatric population. MATERIAL
      AND METHODS: The postsurgical complications of 63 interventions for idiopathic
      scoliosis over a 10-year period were analyzed. Conventional thoracotomy was used
      in 37 interventions (59 %) and thoracoscopy was used in 26 (41 %). RESULTS: In
      patients treated with the thoracolumbar endoscopic procedure, oral nutrition was
      resumed earlier, the mean length of hospital stay was lower, and debit drainage
      or requirement of surgical drainage were lower. CONCLUSIONS: Fewer immediate
      postsurgical complications were observed in scoliosis surgery when thoracoscopy
      was used.

PMID- 17194328
TI  - [Safety of hexavalent combined vaccines and the principle of precaution].

PMID- 17194329
TI  - [Childhood obesity. Recommendations of the Nutrition Committee of the Spanish
      Association of Pediatrics. Part I. Prevention. Early detection. Role of the
      pediatrician].
AB  - Obesity is a pathologic entity characterized by an increase in fat body mass and
      is a global public health problem. In Spain, between 1984 (the Paidos study) and
      2000 (the enKid study), the prevalence of childhood overweight and obesity
      increased and significant differences were found among the autonomous
      communities. Consequently prophylactic measures were implemented throughout the
      country and in 2005 the Ministry of Health developed the NAOS strategy (strategy
      for nutrition, physical activity and obesity prevention). Within the medical area
      of this intervention, primary care pediatricians acquire a key role. Aware of
      this, the Spanish Association of Pediatrics, through the Nutrition Committee,
      aims to provide information on the current situation concerning the
      etiopathogenesis and early identification of at-risk populations. The
      epidemiology and risk periods in the pediatric age group are reviewed and
      recommendations on healthy lifestyle are provided, bearing in mind diet and
      physical activity throughout childhood, with the aim of preventing overweight and
      obesity.

PMID- 17194330
TI  - [Association between WAGR syndrome and diaphragmatic hernia].
AB  - Anomalies in WT-1 (Wilms' tumor gene), mapped to 11p13, cause Denys-Drash,
      Frasier and WAGR syndromes. WAGR syndrome is characterized by Wilms' tumor (W),
      aniridia (A), genitourinary anomalies (G) and mental retardation (R). In the
      early human fetus, WT-1 is expressed in the pleural and abdominal mesothelium,
      and consequently this gene may play a role in diaphragm development. The first
      report of an association between WAGR syndrome and congenital diaphragmatic
      hernia has recently been published. We present another infant with aniridia, left
      cryptorchidism with testicular dysgenesis, right-sided posterolateral
      diaphragmatic hernia and moderate psychomotor retardation, in whom genetic study
      showed a deletion of 11p13 and PAX-6, confirming the diagnosis of WAGR syndrome.

PMID- 17194331
TI  - [An unusual cause of failure of weaning from mechanical ventilation in an
      infant].
AB  - The weaning process is a critical phase in patients undergoing mechanical
      ventilation. This process can be hampered by numerous causes, such as
      neuromuscular diseases and spinal muscular atrophy (SMA). We present a 6-month
      old boy with respiratory distress, fever, marked hypotonia without motor
      developmental milestones, and areflexia. The patient showed progressive
      respiratory distress requiring mechanical ventilation. Definitive weaning was not
      achieved and the boy died from respiratory failure. Partial autopsy was performed
      with a diagnosis of SMA and genetic study of the parents. Neuromuscular diseases
      are an infrequent cause of respiratory insufficiency in suckling infants. The
      differential diagnosis is made between axonal and motor neuron diseases. The
      diagnosis was confirmed by muscular biopsy and genetic study.

PMID- 17194332
TI  - [Idiopathic soft palate hemiparalysis].
AB  - Idiopathic soft palate paralysis is an infrequent clinical entity, both in
      children and adults. We describe the clinical manifestations in two new cases,
      manifested by fluid dysphagia, rhinolalia, absent gag reflex, and nasal escape of
      fluids. The remission period is the shortest observed in published cases. Thirty
      three reports have been published in the literature to data, 32 in children and
      adolescents and one in an adult. This paralysis suggests a viral etiology,
      affects mainly children, and resolves spontaneously.

PMID- 17194333
TI  - [Ebstein's anomaly and lithium exposure during pregnancy].

PMID- 17194334
TI  - [De novo partial monosomy 10p].

PMID- 17194335
TI  - [Brain injury after fetal traumatism due to maternal traffic accident].

PMID- 17194337
TI  - [Hair casts].

PMID- 17194336
TI  - [Life-threatening hemorrhage in the neonate of a rifampicin-treated mother].

PMID- 17194338
TI  - [Neonatal hyperparathyroidism secondary to maternal bariatric surgery].

PMID- 17194340
TI  - [Congenital presentation of nonself-healing Langerhans' cell histiocytosis].

PMID- 17194339
TI  - [Perinatal death in a multiple pregnancy associated with placental chorangiosis].

PMID- 17194342
TI  - [Subcutaneous tumoral mass on the back].

PMID- 17194341
TI  - [Noonan's syndrome caused by a mutation in the PTPN11 gene].

PMID- 17194343
TI  - [Progressive fibrosis of the quadriceps muscle].

PMID- 17194344
TI  - [Pseudomembranous colitis due to Salmonella infection].

PMID- 17194345
TI  - [Henoch-Schonlein purpura due to parvovirus B19].

PMID- 17194346
TI  - [Cupuliform lesions in the oral mucosa].

PMID- 17194347
TI  - [Environmental health: why do others always decide?].

PMID- 17194348
TI  - [New indications and therapeutic objectives for dyslipidemia].

PMID- 17194349
TI  - [Inappropriate multiple medication and prescribing of drugs immobile elderly
      patients living in the community].
AB  - OBJECTIVES: To ascertain and analyse the drug consumption of the immobile
      elderly, as well as the number of potentially inappropriate medications (PIM).
      DESIGN: Cross-sectional study. SETTING: Fourteen rural primary care centres.
      PARTICIPANTS: Non-institutionalised immobile patients, older than 64 years were
      selected by systematic sampling. PRINCIPAL MEASUREMENTS: Review of patients'
      medicine cabinets and noting the daily doses and current number of drugs, as well
      as the origin of the prescription. Identification of PIM (Beers criteria).
      RESULTS: One-hundred forty-three homes visits were made. The mean age was 81.3+/
      7.9 years, of whom 74.8% were women. The most common drugs were: analgesics
      (9.2%), antacids (7.1%), nitrites-calcium antagonists (6.5%), non-steroidal anti
      inflammatories (5.0%), and angiotensin converting enzyme inhibitors (4.7%). The
      percentage of patients who took more than 4 drugs was 76.1%. A PIM was taken by
      35% of the elderly. The most common were: long-acting tranquilisers (41.5%),
      hypnotics (13.8%), digoxin (13.8%), indomethacin (7.7%), and antispasmodics
      (6.1%). In the majority of cases, the prescribing of the PIM was made by the
      family doctor (77.7%). Women took significantly more inappropriate drugs than men
      (0.50+/-0.72 vs to 0.25+/-0.50; P=.001) and those on multiple medication more
      than those not on multiple medication (0.50+/-0.73 vs 0.31+/-0.52; P=.008).
      CONCLUSIONS: The prevalence of inappropriate therapy in the immobile elderly is
      high, therefore an effort must be made to reduce it. Procedures directed towards
      increasing the quality of prescribing could improve the state of health and
      quality of life of these patients.

PMID- 17194350
TI  - [Multi-medication and unsuitable prescription of drugs for elderly patients: are
      we doing what we can?].

PMID- 17194351
TI  - [Problems and solutions in health care for chronic diseases. A qualitative study
      with patients and doctors].
AB  - BACKGROUND: Chronic diseases represent a challenge for health systems and the
      professionals most involved in chronic care. Despite biomedical advances, the
      results of care for chronic problems are not as good as they should be.
      OBJECTIVE: To find out what doctors and patients think of care for some of the
      main chronic illnesses; to detect concrete areas of deficit and lack of
      satisfaction felt by both sides and possible lines of improvement; to raise
      mutual understanding between patients and doctors. PARTICIPANTS: Forty-one
      patients with fibromyalgia or diabetes mellitus, carers for people with
      Alzheimer's and breast cancer patients. Forty-three family doctors involved in
      health care delivery to this kind of patient. METHODS: Four discussion groups.
      Transcription and syntactical, semantic and pragmatic contents analysis, with
      both pre-established and emerging categories of consensus. RESULTS: Patients
      thought, with different nuances as a function of the problem put forward, that
      questions of respectful, human and integrated care, clear and suitable
      information, and consistent follow-up were important and insufficiently covered
      by doctors and health services. Doctors thought that many of their efforts in
      caring for these patients were useless, and thought it important to reconsider
      their clinical responsibilities and the patient-doctor relationship. Doctors
      highlighted the limitations in the health care resources available for working
      with these patients. CONCLUSIONS: To tackle prevalent chronic problems requires,
      in the view of doctors and patients, important modifications that are related
      mainly to the kind of relationship between the two, with new clinical
      responsibilities and certain organisational care delivery features.

PMID- 17194352
TI  - [The use of the Framingham-REGICOR equation in a primary care centre. Impact on
      primary prevention of cardiovascular diseases].
AB  - OBJECTIVES: To evaluate the adequacy of cardiovascular primary prevention by
      calculating cardiovascular risk (CVR) with 2 different equations and to evaluate
      the economic impact of the resulting drug expenditure. DESIGN. By means of a
      transversal study of all the new cases of lipaemia diagnosed, patients were
      classified in 2 CVR categories (> or =20% and <20%). The Framingham-Wilson (FW)
      and Framingham-REGICOR (FR) equations were used to analyse the difference between
      observed treatments (really prescribed) and expected treatments. Costs were
      compared. SETTING: Barceloneta PCC, Barcelona, Spain. PATIENTS: Ninety-two cases
      of lipaemia (2002 and 2003) that met the following inclusion criteria: no
      coronary history, no taking of lipid-lowering drugs, and age between 35 and 74.
      There were 10 losses in the 92 individuals through lack of a variable for
      calculating CVR. RESULTS: According to the clinical criterion, 22 of the 82
      patients were treated with medication (26.82%). The expected proportion of
      patients treated when the FW equation was used was 24.39% (20/82); and was 0%
      (0/82) with the FR equation. On applying the FW equation, it was seen that 12 of
      22 patients treated and 10 of 60 patients not treated did not receive the correct
      drug treatment. If the mean cost per patient treated and per year at the PCC is
      applied to the new cases, there is a 9.09% reduction (euro 479.2) for the FW
      equation and 100% (euro 5271.2) for the FR equation. CONCLUSIONS: The use of one
      or other algorithm for calculating CVR entails pertinent differences in clinical
      practice and expenditure. All patients in primary prevention must receive non
      pharmacological treatment.

PMID- 17194353
TI  - [Public school programme for fissure sealants and its effect on the private
      demand for restorative dentistry for temporary teeth].
AB  - OBJECTIVE: To analyse the effect of a public school odontological programme of
      fissure sealants on the private demand for restorative dentistry for temporary
      teeth. DESIGN: A longitudinal, comparative study was conducted. It had 2 groups,
      control and sealant, with 3 years monitoring. SETTING: Santa Fe Health Area,
      concretely in the local districts (LD) of Santa Fe and Pinos Puente, Granada,
      Spain, starting in the school year 1996/1997. PARTICIPANTS: The sealant group was
      selected from the Santa Fe LD (which had a public programme of fissure sealants)
      (n=129); and the control group (n=120), from Pinos Puente LD. INTERVENTIONS: All
      the school students were examined (+ report issued) in the schools every 6 months
      for 3 years. The sealant group children received at the health centre fissure
      sealants in their first permanent molars. MAIN MEASUREMENTS: The restorations
      performed in temporary teeth for both groups were analysed (x+/-EE) during the
      study at 12, 24, and 36 month follow-up. RESULTS. The sealant group had a
      significantly greater increase in restorative treatment for temporary teeth (P<
      .05) than the Control group at all monitoring points. CONCLUSIONS: A public
      programme of fissure sealants raised private restorative treatment for temporary
      teeth.

PMID- 17194354
TI  - [Experience of the quality improvement plan for the La Mina Health Centre (1989
      2004)].
AB  - OBJECTIVES: To describe how well the problems detected by a quality improvement
      plan (QIP) for a health care team (HCT) were solved; and to analyse the
      identification methods, the quality causes and dimensions affected by the
      problems detected, and the participation of professionals. DESIGN: Descriptive
      study. Evaluation of the situation in December 2004 of the problems identified
      since 1989. SETTING: Urban HCT, with 58 professionals caring for a population of
      18,897 inhabitants in the La Mina District, Barcelona, Spain. PARTICIPANTS: Five
      hundred and thirty problems identified. MAIN MEASUREMENTS: Number and kind of
      detections and problems; identification methods; quality dimensions; causes;
      degree of solution, by method and cause; degree of solution of the QIP (of
      "internal" problems, excluding the problems caused externally or by patients);
      professional participation. RESULTS: In 312 meetings, there were 963 detections
      (annual average, 60.1; SD, 18.8), corresponding to 530 problems (annual average,
      33.1; SD, 12.4). Of these 530 problems, 411 improved (77.5%). Of the 258
      "internal" problems, 225 improved. The degree of solution of the QIP was 87.2%.
      The identification method that detected most problems (53.02% of the total) was
      the active listening of the quality improvement group. The quality dimensions
      most affected by the problems were effectiveness (31.7%) and accessibility
      (20.4%). The most frequent cause of problems and, at the same time, the category
      with the highest improvement rate (81.6%) was internal organization; 83.9% of
      professionals took part in the QIP. CONCLUSIONS: Having a QIP at our centre
      facilitated the management of the quality of care delivery.

PMID- 17194355
TI  - [The response capacity of primary care and the service networks. The case of
      Catalonia's Hospital Consortium].

PMID- 17194356
TI  - [Family medicine in Latin America. Introduction].

PMID- 17194357
TI  - [Family medicine in Ecuador].

PMID- 17194358
TI  - [Family medicine in El Salvador].

PMID- 17194359
TI  - [Family medicine in Mexico, 1954-2006. Background, current situation, and
      perspectives].

PMID- 17194360
TI  - [Bioethics and home care].

PMID- 17194361
TI  - [Patients referred for the first time from family medicine to rheumatology out
      patient clinics].

PMID- 17194362
TI  - [Rain figures and attendance at emergency departments].

PMID- 17194363
TI  - [Pharmaceutical care for immigrants in "Gibraltar field" (area of Spain bordering
      on Gibraltar)].

PMID- 17194364
TI  - [Reflections on our health service].

PMID- 17194365
TI  - [The anti-tobacco law after one year].

PMID- 17194367
TI  - [Let's base primary care guidelines on pragmatic studies].

PMID- 17194366
TI  - [Pharmacological interactions in patients treated with oral anticoagulants in a
      rural health area].
AB  - OBJECTIVES: To estimate the prevalence of drugs that interact with oral
      anticoagulants and establish relationships between variables and haemorrhagic
      complications. DESIGN: Longitudinal, retrospective study of patient
      anticoagulant. SETTING: Colmenar basic health area, Malaga, Spain. PARTICIPANTS:
      Patients on anticoagulants followed up in primary care. MAIN MEASUREMENTS:
      Indications, time of follow-up, value of last prothrombin time (INR),
      complications and therapeutic groups of major use. RESULTS: The 74.2% of the
      patients had a prothrombin time (INR) in the therapeutic range; 16.14% had minor
      complications; 60.2% of the patients complied with the criteria of multiple
      medication and 88.2% complied with the criteria of multiple medication in the
      last 6 months. The drugs used with a higher capacity to interact are: anti-ulcer
      (26.9%), locomotor system (10.7%), cardiovascular drugs (2.2%), lipid lowering
      drugs (8.6%), and antidiabetics (17.2%). The number of drugs used in the last 6
      months is associated with the presence of haemorrhagic complications (odds ratio
      [OR], 1.10). Allopurinol and pantoprazole had a significant relationship with the
      presence of minor haemorrhages (OR, 19.25 and 7.37, respectively). The variables
      associated with the presence of a haemorrhage were: allopurinol (OR, 25.84),
      number of controls with an INR outside the therapeutic range in the last 6 months
      (OR, 1.31) and time on treatment (OR, 1.07). CONCLUSIONS: The percentage of
      patients within the therapeutic range in the last determination of INR indicates
      good quality. The number of minor complications exceeded the consensus standard
      for the control of patients on anticoagulants. The use of drugs with a higher
      capacity for interacting with oral anticoagulants was very high in the anti-ulcer
      and antidiabetic groups. Pharmacological control of patients on anticoagulants is
      necessary and multiple medications should be avoided.

PMID- 17194368
TI  - [Proportion of individuals with indication criteria for bone densitometry and
      frequency of factors of risk of low osseous mass in primary care consultations].
AB  - OBJECTIVE: To find the number of individuals with indication for Bone
      Densitometry in Primary Care, according to the criteria of the WHO, the Agency
      for Evaluating Medical Technology of Catalonia (AETM) and the International
      Committee on Clinical Guides to Osteoporosis (CIGCO), and the frequency of
      factors of risk of low osseous mass. DESIGN: Multi-centre, prospective,
      transversal study. SETTING: Primary care consultations. PARTICIPANTS: Patients
      over 18 (307 women and 139 men) with mean age of 54.3+/-16.8, who attended for
      consultation with an appointment. MAIN MEASUREMENTS: Presence or absence of
      factors relating to each of the indication criteria for bone densitometry.
      RESULTS: A 36.3% of individuals had indication of densitometry under the AETM
      criteria, 76.7% with the WHO criteria, and 50.5% with the CIGCO criteria
      (applicable only to women). Percentages increased with age and were higher for
      women. Concordance between the various criteria was under 37%. CONCLUSIONS: The
      percentage of individuals with indication for bone densitometry was highly
      variable under different criteria. It was greater in women and increased with
      age. Concordance between different criteria was low.

PMID- 17194369
TI  - [Differences in mortality in the over-65s in a health area of the community of
      Madrid].
AB  - OBJECTIVE: To detect the possible differences in risk of mortality of the
      population aged 65 and over in Health Area 11 of the Community of Madrid and to
      explore their relationship with economic factors. DESIGN: Observational,
      retrospective, and ecological-style study. SETTING: Districts and boroughs in
      Health Area 11 of the Community of Madrid, Spain. PARTICIPANTS: People aged 65
      and over. MAIN MEASUREMENTS: The analysed variable was the total deaths occurring
      in the study population during the period 1996-2001. The standardized mortality
      rate (SMR) was calculated. As a social/economic indicator, mean available income,
      stratified in 3 groups, was used. The statistical method used was Poisson
      regression. RESULTS: The mortality rates oscillated between 37.33 and 91.54
      deaths for every thousand inhabitants (SMR ratio, 2.47). In urban areas, in men
      with level 2 income, mortality was 16% less (P=.0406) than the reference group,
      whereas in high-income men it was 20% less (P=.0042). In women the rate was about
      8% less, though this did not attain statistical significance (P=.3039). The
      relationship in semi-rural areas was not demonstrated. CONCLUSIONS: The existence
      of inequalities in the mortality of the population aged 65 or over was
      demonstrated. There was an inverse relationship between mean available income and
      mortality in urban areas.

PMID- 17194370
TI  - [Falls in the elderly in the community: prevalence, consequences, and associated
      factors].
AB  - OBJECTIVE: To find the prevalence, characteristics, and consequences of falls in
      the elderly and related factors. DESIGN. Cross-sectional, descriptive study using
      personal interviews. SETTING: Three health districts in Cordoba city, Spain.
      PARTICIPANTS: A stratified sample of 362 people over 70. MAIN MEASUREMENTS: The
      assessment tools were the WHO questionnaire for the study of falls and the
      EuroQol-5D for the measurement of health-related quality of life. Uni-bivariate
      and multivariate analyses (P< .05) were run. RESULTS: The prevalence of falls was
      31.78% (95% CI, 26.99%-36.6%); 12.98% of subjects had more than one fall in the
      previous year; 55.3% of falls happened at home; 71.8% of the falls had physical
      consequences, with 7.8% fractures; 44.7% of the elderly studied were scared of
      having a new fall, and 22% limited their mobility after the fall. In 30% of cases
      there was contact with the health system, and 3.3% needed hospital admission. The
      factors related to a greater risk of falls were: being older, being a woman,
      widowed, uneducated, with difficulties in moving both arms, suffering space
      disorientation, high drug consumption, and having worse perceived health status.
      CONCLUSIONS: Falls in the elderly living in the community are a frequent problem,
      with important physical, psychological and social consequences.

PMID- 17194371
TI  - [Evolution in consumption of anti-depressants during the years 2002 to 2004].
AB  - OBJECTIVE: To analyse the use of antidepressants from 2002 to 2004 and the length
      of treatment. DESIGN: Cross-sectional, descriptive study of antidepressant drugs
      prescribed through the National Health System during 2002-2004. SETTING: Lleida
      Health Region, Spain. PARTICIPANTS: A total of 54,890 patients received an
      antidepressant drug between 2002 and 2004. MEASUREMENTS: Age, sex, medicine,
      prescription period, centre. RESULTS: The prevalence of antidepressant treatment
      was: 8.4% in 2002 (368,976 inhabitants); 8.6% in 2003 (376,638 inhabitants); and
      8.7% in 2004 (388,148 inhabitants). The increase in antidepressant treatment in
      2004 over 2002 was 9.4%. Prevalence among men was 5.4% and women, 12.7%. The
      distribution according to antidepressant classes was: selective serotonin
      reuptake inhibitors, 73.7%; tricyclic antidepressants, 26.2%; heterocyclic
      antidepressants, 10%, and monoamine oxidase inhibitors, 0.1%. The duration of
      treatment was 1 to 3 months (43%), 4 to 12 months (22.7%), 13 to 24 months
      (14.4%), and over 24 months (19.9%). CONCLUSIONS: A steady increase in the use of
      antidepressants is being observed, predominantly new drugs. Regarding the length
      of treatment, a high proportion of patients are treated for under 4 months, which
      does not follow recent recommendations in the scientific literature for treatment
      of depression. This is a major element of inefficiency in the health system.

PMID- 17194372
TI  - [Patient participation as a strategy to improve quality].

PMID- 17194373
TI  - [Factorial analysis confirming the Spanish version of the Effort-Reward Imbalance
      questionnaire for measuring stress at work].

PMID- 17194374
TI  - [Prevalence and patterns of alcohol consumption in an adolescent population].

PMID- 17194375
TI  - [Critical reading of scientific articles that pharmaceutical industry offers to
      family doctors].

PMID- 17194376
TI  - [Burnout syndrome in family doctors and physician assistants].

PMID- 17194383
TI  - [Mutant-prevention concentration: a new, clinically relevant parameter of
      antimicrobial activity?].

PMID- 17194384
TI  - [Study investigating the activity of several fluoroquinolones against Pseudomonas
      aeruginosa using the mutant prevention concentration].
AB  - INTRODUCTION: The objective of this study was to compare the activity of
      ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin and ofloxacin against
      Pseudomonas aeruginosa by determining the mutant prevention concentration (MPC).
      METHODS: Thirty-four clinical isolates of Pseudomonas aeruginosa causing
      nosocomial infection were studied. MPC values were determined using an inoculum
      of 10(10) cfu/mL on Mueller-Hinton plates with serial dilutions of the
      antibiotics. The microorganisms were classified according to whether the patients
      had been previously treated with fluoroquinolones or not. RESULTS: The
      fluoroquinolone with the lowest MPC values was ciprofloxacin, followed by
      levofloxacin. Analysis of strains from patients previously treated with
      fluoroquinolones showed persistent susceptibility according to the CLSI criteria,
      but with lower activity of all the drugs. CONCLUSIONS: Although the microorganism
      remained susceptible to fluoroquinolones according to classical methods, the
      suitability of using these drugs in patients with severe infection and a history
      of fluoroquinolone use should be evaluated.

PMID- 17194385
TI  - [Evolution of Neisseria meningitidis sensitivity to various antimicrobial drugs
      over the course of chemoprophylaxis during an epidemic outbreak].
AB  - INTRODUCTION: The aim of this study was to assess the evolution of the population
      MICs for various antimicrobial drugs against Neisseria meningitidis isolates
      obtained from asymptomatic carriers during a chemoprophylaxis campaign carried
      out for an epidemic outbreak of meningococcal disease in Nerva, a small town in
      Huelva province (Spain). MATERIAL AND METHODS: A nasopharyngeal carrier study
      including 427 people was carried out to determine the incidence rate of the
      epidemic strain among the general population. On the basis of the results,
      chemoprophylaxis with rifampicin was administered to the population aged 15 to 29
      years (age group showing the highest incidence of the epidemic strain among
      carriers) living in Nerva. Three months later a new carrier study was performed
      (507 people) to evaluate the effects of chemoprophylaxis. Given the evolution of
      the outbreak, seven months later a new intervention was required with
      ciprofloxacin chemoprophylaxis; a second carrier study (399 people) was performed
      two months later to evaluate its effect. RESULTS: The number of strains isolated
      during the three carrier studies was 59 (13.8%), 33 (6.5%), and 22 (5.5%),
      respectively. Analysis of the changes in the MIC50 and MIC90 for the various
      antibiotics from the first to the second carrier study (rifampicin
      chemoprophylaxis) showed statistical differences only in the distribution of
      rifampicin MICs. Similarly, when changes from the second to the third study were
      analyzed (ciprofloxacin chemoprophylaxis), significant variations were detected
      for the cefotaxime MICs. Nevertheless, although there were changes in the MICs,
      the percentages of susceptibility from the beginning to the end of the study did
      not vary. CONCLUSIONS: Massive chemoprophylaxis in the age group with the highest
      incidence of the epidemic strain among carriers did not clearly modify the
      antibiotic susceptibility of the isolates. However, a slight increase in the
      MIC50 and MIC90 was observed for rifampicin after the first chemoprophylactic
      intervention and for cefotaxime at the end of the study. Consecutive
      chemoprophylactic interventions with rifampicin and ciprofloxacin had an impact
      on the percentage of meningococcal carriers in the overall population, with a
      clearly decreasing trend.

PMID- 17194386
TI  - [Activity of fosfomycin against extended-spectrum beta-lactamase producing
      Escherichia coli and Klebsiella pneumoniae].
AB  - INTRODUCTION: Infection due to extended-spectrum beta-lactamase (ESBL)-producing
      microorganisms is an emerging problem in the community; a high proportion of
      these microorganisms have been isolated from urine samples of women with
      uncomplicated urinary tract infections (UTI). The options for oral treatment of
      uncomplicated UTI are limited because of the multiple drug resistance typical of
      ESBL-producing strains. METHODS: The in vitro activity of fosfomycin (FOS) was
      determined against 428 ESBL-producing strains, including 290 (68%) E. coli and
      138 (32%) K. pneumoniae. Activity of fosfomycin was compared with that of
      amoxicillin-clavulanate (AMC), ciprofloxacin (CIP) and cotrimoxazole (SxT). MICs
      of AMC, CIP, and SxT, and detection of ESBL production were tested by the broth
      microdilution method, whereas FOS MICs were determined by the agar dilution
      method. ESBLs were characterized by isoelectric focusing, polymerase chain
      reaction (PCR) and direct sequencing of encoding genes. The genetic relationship
      among the isolates was determined by REP-PCR. RESULTS: Among the 428 ESBL
      producing isolates studied, 417 (97.4%) were susceptible to FOS (MIC < or = 64
      microg/mL). The resistance rate of E. coli to FOS was 0.3%, and was lower than
      resistance to AMC (11.7%), whereas the resistance rate of K. pneumoniae was 7.2%
      and was equal to resistance to AMC. SxT and CIP were the least active antibiotic
      agents against ESBL-producing isolates (sensitivity < 50%). There were no
      differences in fosfomycin activity against strains expressing different types of
      ESBLs. CONCLUSION: Fosfomycin showed maintained activity against ESBL-producing
      strains and did not present co-resistance with other antimicrobial groups.

PMID- 17194387
TI  - [Antimicrobial resistance surveillance: VIRA STUDY 2006].
AB  - INTRODUCTION: The objective of this study was to determine the current
      antimicrobial susceptibility patterns of the most frequent multi-resistant
      bacteria and to analyze any possible changes with respect to the two VIRA studies
      carried out in 2001 and 2004. METHODS: In February 2006, the 40 participating
      hospitals sent the following microorganisms: non-penicillin-susceptible
      Streptococcus pneumoniae (92), methicillin-resistant Staphylococcus aureus (MRSA)
      (290), clinically significant coagulase-negative staphylococci (136), ampicillin
      resistant Enterococcus faecium (89), ampicillin-resistant Haemophilus influenzae
      (67), ciprofloxacin-resistant Escherichia coli (365), Pseudomonas aeruginosa
      (181), and Acinetobacter baumannii (92). The hospitals provided epidemiological
      data on these microorganisms. Susceptibility was determined with a broth
      microdilution method. RESULTS: Among the non-penicillin-susceptible S. pneumoniae
      isolates, the proportion of those ones resistant to this antibiotic showed a
      significant (p < 0.001) decrease (59.8% in 2001, 30.2% in 2004 and 14.3% in
      2006). Among MRSA, we detected one isolate nonsusceptible to linezolid, four
      resistant to quinupristin-dalfopristin and one strain with a vancomycin MIC of 4
      microg/mL. The prevalence of extended-spectrum beta-lactamase-producing E. coli
      was 12.1%. Resistance of A. baumannii to imipenem varied from 27% in the 2001
      2004 period to 47.8% in 2006 (p < 0.005). CONCLUSION: These results again
      emphasize that resistance surveillance systems are an important tool for
      preventing the emergence and spread of multi-resistant pathogens.

PMID- 17194389
TI  - [Identification of Candida species causing vaginitis in Mexican patients].
AB  - INTRODUCTION: The increasing frequency of candidiasis due Candida spp. other than
      C. albicans suggests that these organisms may also have emerged as a cause of
      vaginitis. OBJECTIVE: The aim of this study was to investigate the species of
      Candida most frequently isolated from Mexican patients with vaginal candidiasis.
      MATERIAL AND METHODS: A total of 631 isolates of Candida were identified by the
      API 20C system and standard bacteriological tests. RESULTS: The most frequently
      identified species were C. albicans (39.0%), C. glabrata (35.9%), and C.
      tropicalis (16.2%). CONCLUSIONS: The results of this study show that in addition
      to C. albicans, C. glabrata and C. tropicalis can also be considered important
      vaginal pathogens in Mexican patients.

PMID- 17194388
TI  - [Acute pyelonephritis treated under "home hospitalization." Ten years'
      experience].
AB  - INTRODUCTION: We present the experience of the Vitoria-Gasteiz Hospital at Home
      Unit in the treatment of acute pyelonephritis, including an analysis of potential
      predictors of failure. PATIENTS AND METHODS: A total of 369 episodes of acute
      pyelonephritis without septic shock or renoureteral obstruction are described.
      After initiating intravenous antibiotic therapy in the hospital emergency
      department, all patients were referred to the HH. We analyzed the characteristics
      of the cases and the relationship between several clinical factors and failure of
      HH care, defined as the need to readmit the patient to conventional
      hospitalization. RESULTS: During the study period, 280 women and 89 men (age 16
      88 years) met the inclusion criteria. Mean length of HH stay was 5 days and
      duration of intravenous therapy was 3 days. Sixteen of the 369 cases (4%) had to
      be readmitted to the hospital because of hypotension, vomiting, pain, fever, or
      signs of obstruction on ultrasound or because they requested it (four patients).
      Patients who were readmitted had a higher maximum temperature (mean 39.4 vs. 38.7
      degrees C; p = 0.006) than those who remained at the HH. There were no
      differences between the groups with respect to the other clinical variables
      studied. The evolution of all 16 hospitalized patients was favorable; only one
      required a urological intervention. CONCLUSIONS: Hospital at home care was an
      effective alternative for managing acute pyelonephritis without shock in 96% of
      cases referred by the emergency department, and obviated conventional hospital
      admission, which is usually indicated for this disease.

PMID- 17194390
TI  - [Lipid alterations and cardiovascular risk associated with antiretroviral
      therapy].
AB  - Dyslipidemia is common in HIV-infected patients receiving antiretroviral therapy
      (ART) and it is often associated with the use of specific antiretroviral drugs.
      The phenotypic profile can include elevated triglycerides or cholesterol alone,
      or mixed patterns with varying changes in LDL and HDL lipoproteins, which imply
      different levels of cardiovascular risk. Growing evidence indicates that ART
      associated hyperlipidemia accelerates the development of atherosclerosis and
      coronary heart disease in HIV-infected patients. In recent years, a number of
      retrospective database reviews and prospective cohort studies have reported a
      higher incidence of coronary events in patients receiving ART, which seems to be
      closely related with the presence of dyslipidemia and the duration of exposure to
      ART. Although the clinical benefit of treating ART-related dyslipidemia remains
      unproven, most experts recommend a policy of cardiovascular disease prevention
      and management similar to that used in non-HIV-infected individuals. In addition,
      the use of antiretrovirals associated with a more favorable lipid profile is
      considered. Clinical experience with lipid-lowering therapy in HIV-infected
      patients is still limited, but there is increasing data confirming its efficacy
      and safety in this setting. Drug interactions should be taken into account when
      statins are used in patients receiving protease inhibitors.

PMID- 17194391
TI  - [Prevention of viral hepatitis].
AB  - Prevention of viral hepatitis infection involves health measures designed to
      avert transmission of viral agents and promote the use of gammaglobulin and
      vaccines. The availability of safe drinking water and improvements in quality of
      life result in better individual hygiene; these factors have had the greatest
      impact on hepatitis A prevention. Serum gammaglobulin administration has been
      replaced by vaccinations for pre-exposure, and to a great extent for post
      exposure prophylaxis because of the progressively lower anti-HAV content of
      gammaglobulin and the short duration of the protective effect. Universal
      vaccination in childhood is the recommended measure for controlling hepatitis A.
      Adults belonging to high-risk groups should also undergo vaccination. The
      incidence of hepatitis B has decreased worldwide because of universal vaccination
      programs, initiated in preadolescence and childhood. Prevention of hepatitis C
      requires control of situations in which there is a likelihood of parenteral
      infection with the virus. Post-transfusion hepatitis has been virtually
      eradicated, but considerable effort is still needed to prevent nosocomial
      hepatitis.

PMID- 17194392
TI  - [Chronic lesion in the pinna of the ear for 30 years].

PMID- 17194393
TI  - [Cutaneous nodules. A holiday souvenir].

PMID- 17194395
TI  - [Mycobacterium avium subcutaneous abscess and HIV infection].

PMID- 17194394
TI  - [Osteoarticular infections due to mycobacteria in a university hospital].

PMID- 17194396
TI  - [Neonatal screening for congenital toxoplasmosis by IgM anti-Toxoplasma
      determination in dried blood from the heel].

PMID- 17194397
TI  - [Staphylococcus aureus cholecystitis].

PMID- 17194398
TI  - [New direction in Intensive Medicine: is it realistic to aim that our journal
      reflects the activity of the Spanish-speaking intensive medicine doctors?].

PMID- 17194399
TI  - [Factors associated with the prognosis of mechanically ventilated infants and
      children. An international study].
AB  - OBJECTIVE: Identify factors associated with the survival of pediatric patients
      who are submitted to mechanical ventilation (MV) for more than 12 hours. DESIGN:
      International prospective cohort study. It was performed between April 1 and May
      31 1999. All patients were followed-up during 28 days or discharge to pediatric
      intensive care unit (PICU). SETTING: 36 PICUs from 7 countries. PATIENTS: A total
      of 659 ventilated patients were enrolled but 15 patients were excluded because
      their vital status was unknown on discharge. RESULTS: Overall in-UCIP mortality
      rate was 15,6%. Recursive partitioning and logistic regression were used and an
      outcome model was constructed. The variables significantly associated with
      mortality were: peak inspiratory pressure (PIP), acute renal failure (ARF), PRISM
      score and severe hypoxemia (PaO2/FiO2 < 100). The subgroup with best outcome
      (mortality 7%) included patients who were ventilated with a PIP < 35 cmH2O,
      without ARF, or PaO2/FiO2 > 100 and PRISM < 27. In patients with a mean PaO2/FiO2
      < 100 during MV mortality increased to 26% (OR: 4.4; 95% CI 2.0 to 9.4). Patients
      with a PRISM score > 27 on admission to PICU had a mortality of 43% (OR: 9.6; 95%
      CI 4,2 to 25,8). Development of acute renal failure was associated with a
      mortality of 50% (OR: 12.7; 95% CI 6.3 to 25.7). Finally, the worst outcome
      (mortality 58%) was for patients with a mean PIP >/= 35 cmH2O (OR 17.3; 95% CI
      8.5 to 36.3). CONCLUSION: In a large cohort of mechanically ventilated pediatric
      patients we found that severity of illness at admission, high mean PIP,
      development of acute renal failure and severe hypoxemia over the course of MV
      were the factors associated with lower survival rate.

PMID- 17194400
TI  - [Atrioventricular block in unstable angina. Results of the ARIAM registry].
AB  - OBJECTIVE: Describe the frequency of high degree atrioventricular block (HDAVB)
      in patients with unstable angina (UA), analyze the variables associated with
      their appearance and evaluate whether HDAVB is independently associated with
      increased mortality or increased length of ICU stay. DESIGN: Retrospective
      descriptive study of patients with UA included in the ARIAM registry. SETTING:
      ICUs from 129 hospitals in Spain. PATIENTS: From June 1996 to December 2003 a
      total of 14,096 patients were included in the ARIAM registry with a diagnosis of
      UA. MAIN VARIABLES OF INTEREST: Variables associated with the development of
      HDAVB, variables associated with the mortality of patients with UA, variables
      associated with the length of ICU stay of patients with UA. RESULTS: HDAVB
      frequency was 1%. Development of HDAVB was independently associated with the
      Killip classification and the presence of sustained ventricular tachycardia or
      ventricular fibrillation. Crude mortality of patients was significantly increased
      when HDAVB was present (9% versus 1%, p < 0,001). When adjusted for other
      variables, HDAVB was not associated with increased mortality. Development of
      HDAVB in patients with UA was independently associated with an increase in the
      length of ICU stay (adjusted odds ratio 1.89: 95% confidence interval: 1.33
      5.69). CONCLUSIONS: Patients with UA complicated with HDAVB represent a high-risk
      population with an increased ICU stay.

PMID- 17194401
TI  - [Monitoring ventilatory mechanics].
AB  - Monitoring the mechanical properties (both static and dynamic) of the respiratory
      tract is essential for the diagnosis and prognosis of the disease causing any
      condition and to take the pertinent therapeutic decisions. These measurements can
      maintain a lung function in optimum conditions during mechanical ventilation and
      choose the best time to disconnect the patient. Until recently, monitoring the
      respiration of patients undergoing mechanical ventilation required sophisticated
      and complicated apparatuses or difficult techniques. Instrumentalization of the
      respiratory as a monitor has evolved in such a way that many respirators can
      graphically reproduce in real time the changes that occur in some variables of
      the respiratory cycle. Using these monitoring techniques improves knowledge of
      lung behavior of each patient with ARDS, thus facilitating its management. It may
      also improve decision-making in each individual patient, improving their
      prognosis.

PMID- 17194402
TI  - [What do the patients need from their physicians].

PMID- 17194403
TI  - [Breaking bad news in medicine: strategies that turn necessity into a virtue].
AB  - Breaking bad news is one of physician's most difficult duties. In spite of this,
      communication skills are considered a minor professional ability. Bad news is
      defined as any news that drastically and negatively alters the patient's view of
      his/her future. Patients never forget where, when and what bad news they were
      told. The factors that make communicating bad new difficult may come from the
      sociocultural setting of the patient or the doctor. Randomized studies have shown
      that communication learning skills may cause a positive impact on the person
      giving and receiving the bad news. In order to facilitate this task, a practical
      and dynamic 6-step protocol, described by Baile and Buckman, that may be useful
      for this task, is described.

PMID- 17194404
TI  - [Severe acute asthma: its management in emergency visits and intensive care].
AB  - All patients with asthma are at risk of suffering an acute asthma attack over
      their lifetime, and these may finally be fatal. Hospitalizations and emergency
      department visits and intensive care account for a large proportion of the health
      care cost burden of asthma. Thus, it is especially important to establish plans
      for prevention, education and therapeutic rationalization of primary care that
      establishes the disease and decreases its worsening. The severity of the
      exacerbations may vary from a mild to life threatening. The mortality is
      basically linked to inadequate assessment of the patient's severity. This leads
      to inadequate treatment in the emergency and delay in the patient's
      hospitalization. This review describes the epidemiology, costs, pathophysiology,
      mortality and management of adult acute asthma patients in the emergency
      department and intensive care, especially that related to non-invasive mechanical
      ventilation and conventional forms of mechanical respiratory care, with the
      current changes in its operational strategy.

PMID- 17194405
TI  - [Cardiac resynchronization through a persistent left superior vena cava].
AB  - Cardiac resynchronization therapy is effective in the treatment of patients with
      severe heart failure and intraventricular dysynchrony. However, we are sometimes
      faced with the unexpected presence of a persistent left superior vena cava. We
      report the case of a patient with dilated cardiomyopathy and left ventricular
      dysynchrony in which we implanted a resynchronization pacemaker exclusively
      through a persistent left superior vena cava that did not communicate with the
      right vena cava.

PMID- 17194406
TI  - [Spontaneous splenic rupture as a complication of acute pancreatitis].

PMID- 17194407
TI  - [Congenital bronchobiliary fistula diagnosed in adult age].

PMID- 17194408
TI  - [Ventilate or not ventilate the COPD patient].

PMID- 17194409
TI  - [Images in intensive medicine].

PMID- 17194410
TI  - [Should the obligations of having minimum nurse/patient ratios be regulated by
      law?].

PMID- 17194412
TI  - [Interdisciplinary relationships and humanization in intensive care units].
AB  - OBJECTIVE: To analyze those aspects of the relationship between the health care
      team of an ICU that may be decisive in the construction of humanized care.
      METHOD:  DESIGN: phenomenology: descriptive and exploratory. ANALYSIS and
      observation unit: Polyvalent 23-bed adult ICU. DATA COLLECTION: nine extensive
      interviews. POPULATION: healthcare professionals in interaction in the ICU that
      is being studied. ANALYSIS: assigning of data to emergent categories. Contrasting
      with existing theories. RESULTS: Identification of guideline values circumspect
      to the humanistic paradigm. The value of professional role is accepted as
      emergency factor of certain attitudes. All the professional groups detect lack of
      independence situations, which are not always attributable to hierarchical
      reasons. Systematic interdisciplinary communication is evaluated positively.
      Humanization requires time, resources, and intergroup relationships and explicit
      commitment by the institution. CONCLUSIONS: Relief of great suffering situations
      is the main reason for interdisciplinary disagreement. Construction of a tolerant
      setting and institutional recognition as factors favoring humanized care. Lack of
      time and resources as obstacles to the humanization of care.

PMID- 17194413
TI  - [Measurement of residual gastric volume: in search of better evidence].
AB  - INTRODUCTION: Measurement of residual gastric volume is a frequent practice in
      chronic patients, but there is lack of consensus on the convenience of
      reintroducing or discarding aspirated gastric content (AGC). OBJECTIVE: Determine
      the grade of scientific evidence on the efficacy of two interventions 
      reintroduction/rejection- of AGC in chronic patients. MATERIAL AND METHODS:
      Systematic review of the evidence available on the convenience of reintroducing
      or discarding ACG. PROCEDURE: a) establishment of inclusion/exclusion criteria;
      b) determination of the search strategy (keywords and itineraries); c) dumping of
      databases: MEDLINE, CINAHL, CUIDEN, IME, SCIELO and COCHRANE. Search for indirect
      method and manual dumping of indexes; d) independent and contrasted critical
      reading, using the CASPe template; and e) contrast of critical analysis results.
      RESULTS: Search itineraries generate more than 800 references that once purged
      make it possible to select 54. After reading them, only 4 really focused on the
      questions related with the reintroduction/rejection of AGC: 2 revisions, 1
      observational study and a random clinical trial with a small sample. Meta
      analysis techniques could not be used due to the heterogeneity of these studies.
      Thus, the results of the study were analyzed separately. Using this procedure, a
      final result was obtained that showed a low grade of scientific evidence.
      CONCLUSIONS: There is limited scientific evidence on the convenience, safety and
      benefits of both interventions. It is difficult to establish a care protocol, so
      that we suggest performing an experimental study to establish the indications and
      contraindications of both interventions.

PMID- 17194414
TI  - [Incidents of cutaneous alteration secondary to external electrical
      cardioversion].
AB  - External electrical cardioversion is a technique basically used as treatment of
      choice in supraventricular arrhythmias, atrial fibrillation standing out for its
      frequency. This procedure consists in the application of one or several
      synchronized electrical discharges through the patient's chest to revert cardiac
      rhythm to sinus rhythm. One of the complications is generally the appearance of
      the skin alterations, pain or intense local heat. The objectives of this study
      were to describe the skin lesions that appeared after an external electrical
      cardioversion procedure and to evaluate the information received by the patients
      on discharge. A descriptive study was conducted, using a sample of 68 patients
      who underwent cardioversion between January 1 and December 30 1, 2004. Mean age
      was 62.71 years, of which 76.5% were males diagnosed of atrial fibrillation in
      82.4% of the cases. Erythema appeared in more than 80% of the cases, with the
      mean duration of 4.76 days. A total of 13.2% developed second-degree burn.
      Although 92.5% considered written information on the care after the procedure
      necessary, less than 11% had received it. It is concluded that the prevalence of
      the skin alterations after cardioversion is elevated, one of the causal factors
      being lack of information. There is a significant deficiency of knowledge on skin
      care after the procedure.

PMID- 17194415
TI  - [Equity and variability in the use of medical technologies].

PMID- 17194416
TI  - [Improving literature searches. Geographic filters, methodology filters. Two
      different algorithms, two different applications].

PMID- 17194417
TI  - [Percutaneous treatment of heart valves].

PMID- 17194418
TI  - [Variations among Spanish regions in the use of three cardiovascular
      technologies].
AB  - INTRODUCTION AND OBJECTIVES: There is evidence that some geographic variations in
      the use of medical technologies are not explained by differences in disease
      burden. The objectives of this study were to quantify variability in the use of
      percutaneous coronary intervention (PCI), implantable cardioverter-defibrillators
      (ICDs), and cardiac resynchronization therapy (CRT) in Spanish autonomous regions
      and to try to explain the variability found for the first two technologies.
      METHODS: Linear regression models were developed in which the number of
      procedures performed per million population (pmp) in 2003 in each autonomous
      region was the dependent variable. Independent variables used included indices of
      technology provision, regional wealth, and disease burden. RESULTS: For PCI, the
      mean utilization rate for the whole of Spain was 1038 procedures pmp, with a high
      low ratio of 1.95. Differences in gross domestic product explained 21% of the
      variability, but there was no relationship between the number of procedures
      performed and disease burden. For ICDs, the mean number of procedures performed
      in the whole of Spain was 46 pmp, with a high-low ratio of 3.04. As for PCI,
      differences in regional wealth explained 40% of the variability, with disease
      burden making no contribution. For CRT, the mean number of procedures performed
      in Spain in 2003 was 15 pmp, with a high-low ratio of 15.7. CONCLUSIONS: The
      considerable regional variation that exists in the use of these three medical
      technologies is principally explained by differences in regional wealth and not
      in disease burden.

PMID- 17194419
TI  - [Development of a geographic filter for PubMed to identify studies performed in
      Spain].
AB  - INTRODUCTION AND OBJECTIVES: The increasing size of the PubMed (Medline) database
      has made it necessary to develop specific tools for information retrieval (i.e.,
      filters). The current configuration of the Limits option in PubMed does not
      enable searches to be limited according to geographic criteria. Our objectives,
      therefore, were a) to develop a geographic filter for the retrieval from PubMed
      of studies performed in the Spanish population, and b) to assess its performance.
      METHODS: A second-generation filter was constructed by reviewing previous
      strategies. It involved the selection of three types of record that included: a)
      the term Spain in different languages; b) Spanish place names (i.e., mainly those
      of autonomous regions and provinces), and c) acronyms for health services in
      autonomous regions. The performance of the filter (i.e., its sensitivity and
      specificity) was assessed in a representative sample (i.e., clinical trials
      indexed in PubMed under the MeSH term Myocardial Infarction) by comparison with
      the results of a manual search (the gold standard). In addition, the filter's
      performance was also evaluated by comparing it with a simple search for the term
      Spain[ad]. RESULTS: Use of the filter retrieved 74 (98.7%) of the relevant
      references. The sensitivity (88.1%) was higher than that of the simple search
      strategy (45.8%), and excellent specificity (100%) was achieved in both cases.
      CONCLUSIONS: A geographic filter has been developed for identifying studies in
      PubMed that involve the Spanish population.

PMID- 17194420
TI  - [Gender differences in adiponectin and leptin expression in epicardial and
      subcutaneous adipose tissue. Findings in patients undergoing cardiac surgery].
AB  - INTRODUCTION AND OBJECTIVES: The high level of metabolic activity present in
      visceral adipose tissue is associated with the development of atherothrombosis.
      Subcutaneous adipose tissue secretes larger quantities of the adipocytokines
      leptin and adiponectin than visceral adipose tissue. Epicardial adipose tissue
      secretes inflammatory mediators, and the resulting proinflammatory activity is
      greater than that associated with subcutaneous adipose tissue. The aim of this
      study was to compare adiponectin and leptin expression in human epicardial and
      subcutaneous adipose tissue. METHODS: Samples of both epicardial and subcutaneous
      adipose tissue were taken from 46 patients who were undergoing heart surgery,
      coronary artery bypass surgery, or aortic or mitral valve replacement. Levels of
      protein and gene expression of leptin and adiponectin were assessed
      immunohistochemically and by RT-PCR, respectively. Levels of mRNA expression in
      the 2 adipose tissue types were compared by real-time quantitative PCR. RESULTS:
      Significant differences were found between adiponectin and leptin mRNA expression
      in epicardial and subcutaneous adipose tissue, with epicardial adipose tissue
      exhibiting lower levels of adiponectin and leptin expression. Moreover,
      adiponectin and leptin mRNA expression in epicardial adipose tissue was higher in
      women than men. CONCLUSIONS: Adiponectin and leptin expression is lower in
      epicardial than in subcutaneous adipose tissue. Moreover, there are differences
      in adiponectin and leptin expression in epicardial adipose tissue between women
      and men.

PMID- 17194421
TI  - [Safety of early cardiac magnetic resonance imaging in acute myocardial
      infarction patients with stents].
AB  - INTRODUCTION AND OBJECTIVES: In general, magnetic resonance imaging is
      contraindicated when the patient has a ferromagnetic prosthesis or implant. With
      coronary stents, there is a theoretical concern that use of magnetic resonance
      imaging shortly after implantation will dislodge the stent, thereby increasing
      the risk of thrombosis. However, the risk may be overestimated because modern
      coronary stents are not ferromagnetic or are only weakly so. The objective of
      this study was to determine whether carrying out cardiac magnetic resonance
      imaging shortly after stent implantation is a safe procedure in acute myocardial
      infarction patients. METHODS: We carried out a retrospective study of 407
      patients with ST-elevation acute myocardial infarction who were treated by stent
      implantation. Cardiac magnetic resonance imaging was performed in the first 14
      (11) days after stent implantation in 86 of these 407 patients (group 1); it was
      not performed in the 321 patients in group 2. The occurrence of an adverse event,
      such as death, reinfarction, or revascularization, either in hospital or after 6
      or 12 months was recorded. RESULTS: Three patients experienced subacute stent
      thrombosis, all in group 2. No statistically significant difference in any other
      variable was found. The combined rate of death, reinfarction, revascularization,
      or rehospitalization at 12 months was 14% in group 1 and 16% in group 2 (P=.7).
      CONCLUSIONS: Carrying out cardiac magnetic resonance imaging shortly after stent
      implantation in acute myocardial infarction patients appears to be a safe
      procedure.

PMID- 17194422
TI  - [Influence of admission glucose level on long-term prognosis in patients with
      acute coronary syndrome].
AB  - INTRODUCTION AND OBJECTIVES: Hyperglycemia can increase the risk of death or a
      poor outcome following myocardial infarction. Our objective was to investigate
      the value of the admission glucose level in predicting long-term outcome in
      patients with acute coronary syndrome. METHODS: The study population comprised
      565 patients admitted with acute coronary syndrome within 24 hours of the start
      of symptoms. The final diagnosis was myocardial infarction in 56% and unstable
      angina in 44%. RESULTS: The patients' mean glucose level was 143 (77) mg/dL.
      During follow-up (42 [6] months), 55 (9.7%) patients died. The area under the
      receiver operating characteristic curve for the optimum cut point for predicting
      death from the glucose level was 0.67; the cut point was 128 mg/dL, with a
      sensitivity of 85% and a specificity of 62%. Patients were divided into 2 groups
      according to blood glucose level: in group 1 (36.8%), it was > or = 128 mg/dL; in
      group 2, <128 mg/dL. There were differences between the groups in the incidence
      of diabetes (47.2% vs 12.6%; P< .001), systolic blood pressure (138 [33] mm Hg vs
      133 [33] mm Hg; P< .001), and ejection fraction (48.3 [0.9]% vs 55.2 [12.4]%;
      P=.004). At 4 years, the survival rates were 40% and 77% in groups 1 and 2,
      respectively (log rank test P< .001). The following were independent predictors
      of mortality: admission glucose level > or =128 mg/dL (hazard ratio [HR= 2.41;
      P=.021), admission systolic blood pressure (HR= 0.97; P< .001), admission
      troponin-T level (HR=4.88; P< .001), and the development of heart failure
      (HR=1.04; P=.001). A rise of 10 mg/dL in glucose level was associated with a 2.56
      fold increase in the risk of death (P=.012). CONCLUSIONS: In patients with acute
      coronary syndrome, hyperglycemia at admission (cut point > or =128 mg/dL) was
      associated with increased long-term risk and, in addition, was a strong
      independent predictor of mortality.

PMID- 17194424
TI  - [Spanish Heart Transplantation Registry. 17th official report of the Spanish
      Society of Cardiology Working Group on Heart Failure, Heart Transplantation, and
      Associated Therapies (1984-2005)].
AB  - INTRODUCTION AND METHODS: This article summarizes the general characteristics of
      heart transplantation in Spain and the results achieved, once data for 2005 have
      been included. RESULTS: In the course of the last year, 287 heart
      transplantations were performed, which brings the total to 4967 since 1984.
      Clinically, the typical Spanish heart transplant patient is male, aged about 50
      years, has blood group A or O, has non-revascularizable coronary disease or
      idiopathic dilated cardiomyopathy, and is in New York Heart Association
      functional class IV/IV. The percentage of emergency heart transplants carried out
      was 22%, which is considerably lower than in the previous year (i.e., 35%) and
      slightly lower than the average for the last 5 years (i.e., 23%). The early
      mortality rate was 10%, which is similar to that in the previous year and lower
      than the average for the last 5 years (i.e., 12%). After adding the 2005 results
      to those of previous years, the survival probabilities at 1, 5, and 10 years were
      75%, 65%, and 50%, respectively. On calculating survival curves for separate
      historical periods, a significant improvement could be seen for the last 5 years,
      in which the 1- and 5-year survival probabilities were 80% and 70%, respectively.
      The most frequent cause of death in the first month was acute graft failure; in
      the first year, infection and rejection were most common; and, in the long term,
      tumors and the combination of graft vascular disease with sudden death.
      CONCLUSIONS: Comparative analysis of survival rates showed that short-, medium
      and long-term outcomes in Spain are consistent with those reported in the world
      literature, including a continuing trend towards better survival over the years.

PMID- 17194423
TI  - [Prognostic value of discharge hemoglobin level in patients hospitalized for
      acute heart failure].
AB  - INTRODUCTION AND OBJECTIVES: Recent studies show that the prevalence of anemia in
      patients with heart failure is high and indicate that its presence leads to
      increased mortality and morbidity. Our aims were to determine the prevalence of
      anemia in patients hospitalized for heart failure and to study the long-term
      prognostic significance of anemia by evaluating its relationship with mortality
      (total and due to heart failure) and readmission for heart failure. METHODS: The
      study included 242 consecutive patients admitted to our cardiology department and
      discharged with a diagnosis of congestive heart failure. The Kaplan-Meier
      technique and Cox regression modeling were used to determine whether anemia is an
      independent predictor of death or readmission for heart failure. Anemia was
      defined as a hemoglobin level <12 g/dL. The mean follow-up period was 23.5 (10.9)
      months. RESULTS: Overall, 79 patients (32.6%) were anemic. During follow-up, 77
      died (53 due to heart disease) and 117 were readmitted for heart failure.
      Multivariate analysis showed that anemia was an independent predictor of death
      (hazard ratio [HR]=1.85, 95% confidence interval [CI], 1.12-3.06), death due to
      heart disease (HR=1.88, 95% CI, 1.03-3.45), and readmission for heart failure
      (HR=1.87, 95% CI, 1.28-2.74). CONCLUSIONS: The prevalence of anemia was high in
      patients hospitalized for heart failure. Moreover, a discharge hemoglobin level
      less than 12 g/dL was a predictor of all-cause death, cardiac death, and
      readmission for heart failure.

PMID- 17194425
TI  - [Spanish registry of implantable cardioverter defibrillator. Second official
      report of the Spanish Society of Cardiology Working Group on Implantable
      Cardioverter Defibrillators (2005)].
AB  - INTRODUCTION AND OBJECTIVE: We report the results for the Spanish Registry on
      Implantable Cardioverter Defibrillators (ICD) (year 2005), developed by the
      Working Group on ICD of the Spanish Society of Cardiology. METHODS: Data were
      collected (prospectively in 77% of implants) by single page form questionnaires
      transmitted after the procedure to the Spanish Society of Cardiology.
      Participation was voluntary. RESULTS: The number of implants sent to the Registry
      was 2050 and this represents 74.4% of the total ICDs implanted. The implantation
      rate per million was 46.5 and the estimated total implantation rate per million
      was 62.5. The proportion of first implants was 70.3%. The majority of patients
      were males, with a median age of 65 years, severe or moderate to severe left
      ventricular dysfunction and in functional class II or I. Ischemic heart disease
      was the more frequent underlying heart disease followed by dilated
      cardiomyopathy. The main reason for ICD indication was secondary prevention
      related to sustained monomorphic ventricular tachycardia or aborted sudden
      cardiac death. A significant number of prophylactic indications were done,
      specially in non ischemic heart disease. The proportion of ICD implanted at the
      electrophysiology laboratory by cardiac electrophysiologist continues increasing.
      There was an increase in the number of ICD plus cardiac resynchronization
      therapy, that represent a 23.6% of the implants. The incidence of complications
      during the implant was very low. CONCLUSIONS: The National Registry on ICD, with
      a participation rate greater than in previous years, provides a representative
      sample of the ICD implants performed at our country.

PMID- 17194426
TI  - [Spanish pacemaker registry. Third official report of the Spanish Society of
      Cardiology Working Group on Cardiac Stimulation (2005)].
AB  - INTRODUCTION: The aims of this article were to summarize data on pacemaker
      implantation reported to the Spanish Pacemaker Registry for 2005 and to provide
      an analysis of the various electrocardiographic phenomena that lead to pacemaker
      implantation. METHODS: Data were collected using the European Pacemaker
      Identification Card, with each center individually deciding whether to send the
      card itself or to submit data in an electronic format. RESULTS: In total, 82
      participating centers submitted a total of 9156 cards, which corresponds to 31.9%
      of pacemakers estimated to have been implanted that year. The average age of
      patients who received their first implant remained approximately 75 years and, as
      in previous years, they were more frequently male. In the majority of cases, the
      indication was atrioventricular block, followed by sick sinus syndrome and then
      by atrial fibrillation or flutter with atrioventricular block or bradycardia. In
      1.35% of the sample analyzed, biventricular stimulation was used for
      resynchronization. Some 79% of pacemakers were rate-responsive. In practice, all
      pacemakers used bipolar leads. CONCLUSIONS: It was observed that the pacing modes
      selected were better suited to the various electrocardiographic abnormalities
      that resulted in pacemaker implantation, in accordance with cardiac stimulation
      guidelines. In the absence of persistent atrial arrhythmia, age had the greatest
      influence on pacing mode selection. The more frequent use of pacemakers in males
      was almost exclusively due to the higher incidence of conduction disorders.

PMID- 17194427
TI  - [Spanish Society of Cardiology ethical framework (executive summary)].
AB  - The Spanish Society of Cardiology (SEC) has produced an Ethical Framework
      Document. This document is divided into two distinct parts that deal,
      respectively, with the responsibilities of the SEC as an organization and the
      responsibilities of its professional members. The SEC makes recommendations on
      how its members should carry out their daily clinical practice, provides a
      professional perspective on public commitments as a scientific association, and
      aims to ensure that any views, recommendations, and advice expressed provide the
      basis for an informed debate on ethical problems in our field of work.

PMID- 17194428
TI  - [Guidelines for management of patients with ventricular arrhythmias and the
      prevention of sudden cardiac death. Executive summary].

PMID- 17194430
TI  - [Scimitar syndrome: application of magnetic resonance angiography].

PMID- 17194429
TI  - [Guidelines for the management of patients with atrial fibrillation. Executive
      summary].

PMID- 17194431
TI  - [Incidence of hypertension in a cohort of Spanish university graduates: the SUN
      study].
AB  - Hypertension is a major public health problem. However, no estimates of age- and
      sex-specific incidences are available for the Spanish population. Our objective
      was to estimate the incidence of hypertension in a cohort of university graduates
      in Spain. We followed up 5648 individuals aged 25-65 years who were initially
      free of hypertension, diabetes, and cardiovascular disease for a median of 30
      months. New diagnoses of hypertension were identified using mailed
      questionnaires. We verified all self-reported diagnoses of hypertension. In 18
      250 person-years of follow-up, we identified 248 new cases of hypertension. The
      unadjusted incidences of hypertension in women and men were 8.2 per 1000 person
      years (95% CI, 6.7-10.1) and 21.8 per 1000 person-years (95% CI, 18.6-25.4),
      respectively. The cumulative probability of receiving a medical diagnosis of
      hypertension by the age of 65 years was 50% among women and 72% among men. In
      conclusion, we have provided new evidence confirming that hypertension is one of
      the most important public health problems in Spain.

PMID- 17194432
TI  - [Influence of gender on the etiology of mitral regurgitation].
AB  - Our aim was to investigate the prevalence of the different causes of severe
      mitral regurgitation and the influence of gender on that prevalence. We performed
      a prospective study of 272 consecutive patients with severe mitral regurgitation
      that had been detected echocardiographically. Their mean age was 70.2 (13.8)
      years, and 143 were women (52.6%). Atrial fibrillation was present in 52.9%,
      72.7% presented with heart failure, and 21.0% with previous myocardial
      infarction. The most common etiological factor was rheumatic disease (in 26.5%),
      with the etiology being unclear in 32 patients (11.8%). Rheumatic disease was
      more frequent in women, at 35.7%, than in men, at 16.3%, whereas other etiologies
      were less frequent in women (P< .001). In all age groups, a rheumatic etiology
      was more frequent in women. Rheumatic heart disease remains the main cause of
      severe mitral regurgitation observed in women referred to hospitals similar to
      ours.

PMID- 17194433
TI  - [Safety of aspirin, clopidogrel, and acenocumarol combination in patients
      requiring anticoagulation].

PMID- 17194434
TI  - [Aborted sudden death secondary to recurrent transient apical dyskinesia].

PMID- 17194435
TI  - [Sildenafil treatment of unilateral pulmonary edema and pulmonary hypertension in
      pulmonary artery agenesis].

PMID- 17194436
TI  - [Fasting glucose versus oral glucose tolerance testing in the diagnosis of
      diabetes mellitus].

PMID- 17194437
TI  - Repeated infections with Schistosoma mansoni and liver fibrosis in undernourished
      mice.
AB  - The mouse model of schistosomal periportal fibrosis (Symmers' "pipestem"
      fibrosis), that develops in 30-50% of the infected animals, is not reproduced in
      undernourished mice. Host nutritional status is likely to be a variable that may
      influence the outcome and progression of infection, since it interferes with the
      dynamics of connective tissue changes occurring in chronic hepatic
      schistosomiasis. Re-infections increase the occurrence of periportal liver
      fibrosis in well-nourished animals, but it is not known how undernourished mice
      would behave being repeatedly re-infected. So, 21-day-old male albino Swiss mice
      were individually exposed to 30 cercariae (percutaneous route) of the BH strain
      of Schistosoma mansoni, 4 weeks after being on a low-protein diet. Control
      animals were fed on a commercial balanced chow for mice. The nutritional status
      was evaluated by body weight gain and measurement of food intake. Mice were
      divided into four groups: A1 (undernourished, single infected), A2 (well
      nourished, single infected), B1 (undernourished, re-infected), B2 (well
      nourished, re-infected). The primary infection was performed 4 weeks after
      ingesting the respective diet. Re-infections started 45 days later, with exposure
      to 15 cercariae, at 15 day intervals. Mice were sacrificed 18 weeks after the
      primary exposure. The livers were submitted to morphological (gross and
      microscopic pathology), morphometric (percentage of fibrosis; granuloma size;
      volume and numerical densities) by using semi-automatic morphometry, and
      biochemical (quantification of collagen as hydroxyproline) studies. Worm burdens
      and hepatic egg counting were also recorded. Values for body weight gains were
      always lower in undernourished mice, the effects of re-infection being minimal on
      this regard. Liver and spleen weights were higher in well-nourished mice (either
      single infected or re-infected) and mainly related to the type of ingested diet.
      A greater number of re-infected well-nourished mice developed periportal
      fibrosis, but undernourished re-infected animals did not reproduce this lesion.
      The percentage of fibrosis and hepatic collagen content were higher in well
      nourished mice, but differences between single infected and re-infected groups
      were not statistically significant.

PMID- 17194438
TI  - A comparative analysis of strategies for isolation of matrix vesicles.
AB  - Matrix vesicles (MVs) are extracellular organelles involved in the initial steps
      of mineralization. MVs are isolated by two methods. The first isolation method of
      MVs starts with collagenase digestion of osseous tissues, followed by two
      differential centrifugations. The second isolation method does not use proteases
      but rather starts with differential centrifugation, followed by a fractionation
      on a sucrose gradient. The first method results in a homogeneous population of
      MVs with higher cholesterol/lipid content, alkaline phosphatase activity, and
      mineral formation rate as compared with MVs isolated by the second method. The
      second method leads to higher protein diversity as compared with MVs isolated
      according to the first method. Due to their distinct protein composition, lipid
      to-protein and cholesterol-to-phospholipid ratios, and differences in rates of
      mineral formation, both types of isolated MVs are crucial for proteomic analysis
      and for understanding the regulation of mineralization process at the molecular
      level.

PMID- 17194439
TI  - Learning curve analysis of a patient lift-assist device.
AB  - One of the challenges facing ergonomists in the implementation of an ergonomic
      solution is addressing the concerns related to their impact on productivity. The
      focus of the current study was to (1) apply standard learning curve analysis to
      the learning that takes place as an individual works with a patient handling
      device and (2) compare the effects of two different training protocols on
      measures of learning. Eighteen subjects completed 11 replications of a patient
      transfer task after participating in either an "interactive" training protocol or
      "see-one-do-one" training protocol. The results show that the learning rate for
      this task was 83% with no difference as a function of training protocol. The
      results do indicate that the effect of Training Method was significant (p<0.05)
      for time to complete the first patient lift task (370s for the interactive
      training vs. 475s for see-one-do-one training). The results of the analysis of
      the survey data supported the objective results in that the only measure that was
      responsive to training type (p<0.05) was related to comfort level in performing
      the patient lift task for the first time. The results emphasize the importance in
      considering learning when introducing an intervention in the workplace, and
      showed that in this instance, training type had an immediate impact on
      productivity, but that this effect diminished over time.

PMID- 17194440
TI  - Molecular and functional characterization of a cyclophilin with antifungal
      activity from Chinese cabbage.
AB  - An antifungal protein that inhibits the growth of filamentous fungal pathogens
      was isolated from Chinese cabbage (Brassica campestris L. ssp. pekinensis) by
      affinity chromatography on Affi-gel blue gel and ion exchange chromatography on
      CM-Sepharose. The N-terminal amino acid sequence of the protein was highly
      homologous to that of plant cyclophilins and consequently the protein was denoted
      as C-CyP. To understand the antifungal activity of C-CyP, we isolated a cDNA
      encoding its gene from a Chinese cabbage leaf cDNA library. The Chinese cabbage
      genome bears more than one C-CyP gene copy and C-CyP mRNA is highly expressed in
      all tissues except the seeds. Recombinant C-CyP catalyzed the cis-trans inter
      conversion of the Ala-Pro bond of the substrate, which indicates this protein has
      peptidyl-prolyl cis-trans isomerase activity. It also inhibited the growth of
      several fungal pathogens.

PMID- 17194441
TI  - Anti-enterovirus activity and structure-activity relationship of a series of 2,6
      dihalophenyl-substituted 1H,3H-thiazolo[3,4-a]benzimidazoles.
AB  - Despite the fact that enteroviruses are implicated in a variety of human
      diseases, there is no approved therapy for the treatment of enteroviral
      infections. Here, a series of 2,6-dihalophenyl-substituted 1H,3H-thiazolo[3,4
      a]benzimidazoles with anti-enterovirus activity is reported. The compounds elicit
      potent activity against coxsackievirus A9, echovirus 9 and 11 and all six strains
      of coxsackievirus B. A structure-activity relationship analysis revealed that the
      presence of substituents at position 6 of the tricyclic system positively
      influences the antiviral activity, whereas substitutions at position 7 are less
      favorable. In particular a 6-trifluoromethyl substitution leads to a substantial
      improvement of the antiviral activity as compared to the unsubstituted structure.
      Furthermore, an additional introduction of a 2-Cl, 6-F substitution on the phenyl
      at C-1 results in a further increase of the antiviral activity. Hence, 1-(2
      chloro-6-fluorophenyl)-6-trifluoromethyl-1H,3H-thiazolo[3,4-a]benzimidazole
      results in a dose-dependent inhibition of viral replication with a 50% effective
      concentration (EC50) of 0.41 microg/ml without any detectable cytotoxicity at the
      highest concentration (100 microg/ml) tested.

PMID- 17194442
TI  - Neuronal proteins involved in synaptic targeting of AMPA receptors in rat
      hippocampus by antidepressant drugs.
AB  - Recent data suggest that the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) glutamate receptor subtype plays a pivotal role in the pathogenesis
      of effective disorders and in the action of antidepressant drugs. After chronic
      treatment with the antidepressants desipramine or paroxetine, we measured by
      immunoprecipitation and Western blotting, the changes in the interaction of AMPA
      receptor subunits with proteins involved in trafficking and/or stabilization of
      the subunits into synaptic membranes of the hippocampus. Both antidepressants
      increased the interaction of GluR1 subunit with stargazin and of GluR2/3 with
      NSF. Paroxetine increased the interaction of GluR1 with Rab4A, and desipramine
      markedly increased the interaction of GluR1 with SAP97. Paroxetine, but not
      desipramine, also increased membrane levels of CaMKII, autophosphorylated CaMKII
      and GluR1 phosphorylated at the CaMKII site. Interactions of GluR1 and GluR2/3
      with proteins implicated in AMPA receptor trafficking and with scaffolding
      proteins appear to account for the enhanced membrane expression of AMPA receptors
      in the hippocampus after antidepressant treatment.

PMID- 17194443
TI  - Obesity-induced upregulation of myocardial endothelin-1 expression is mediated by
      leptin.
AB  - Several studies have shown that leptin, the product of the obese gene, may link
      obesity with cardiovascular diseases, and in particular with cardiac hypertrophy.
      In vitro studies suggest that the mechanism by which leptin causes cardiac
      hypertrophy involves the upregulation of endogenous endothelin-1 (ET-1), a potent
      vasoconstrictor and mitogen. Whether obesity-associated hyperleptinemia causes an
      increase in myocardial ET-1 expression in vivo remains unclear. To address this
      issue, we fed mice with a high-fat diet and analyzed serum levels of ET-1 and ET
      1 mRNA in the heart. We found that in mice fed a high-fat diet, serum ET-1,
      myocardial ET-1, leptin and leptin receptor mRNA were all elevated. In contrast,
      in leptin-deficient obese (ob/ob) mice, both serum and myocardial ET-1 levels
      were not higher than in wild type mice. These findings suggest that upregulation
      of myocardial ET-1 by obesity is mediated by leptin.

PMID- 17194445
TI  - IL-12 p35 silenced dendritic cells modulate immune responses by blocking IL-12
      signaling through JAK-STAT pathway in T lymphocytes.
AB  - Dendritic cells (DC) constitute a complex system of uniquely specialized antigen
      presenting cells (APC) that play crucial roles in the initiation and regulation
      of immune responses. Recent studies have demonstrated that DC silenced by siRNA
      IL-12 p35 showed tolerogenic capacity in vitro. However, their mechanism of
      action is not fully understood. In this study, IL-12p35 siRNA was chemically
      synthesized and transfected into DCs. A coculture of T cells and DCs was
      performed. After 30 min coculture, T cells were harvested and analyzed. We showed
      that the IL-12 p35 silenced DCs decreased IL-12-induced T cell responses through
      blocking tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 proteins in T
      cells. These results demonstrate IL-12 p35 silenced DCs modulate immune responses
      by blocking IL-12 signaling through JAK-STAT pathway in T cells.

PMID- 17194444
TI  - Human SLUG does not directly bind to CtBP1.
AB  - SLUG is a transcriptional repressor protein implicated to have major role in the
      oncogenesis and metastasis of human breast cells. We previously have shown by
      chromatin immunoprecipitation assay that human SLUG (hSLUG) is co-localized with
      the co-repressor protein CtBP1 as bound to the BRCA2 gene silencer [M.K.
      Tripathi, S. Misra, S.V. Khedkar, N. Hamilton, C. Irvin-Wilson,, C. Sharan, L.
      Sealy, G. Chaudhuri, J. Biol. Chem. 280 (2005) 17163-17171]. hSLUG was predicted
      to be binding directly to CtBP1 because of an apparent presence of CtBP1 binding
      site in its amino acid sequences. Here, we provide evidence through yeast two
      hybrid and in vitro co-immunoprecipitation analyses that hSLUG does not directly
      interacts with hCtBP1. This observation will help in the study of the mode of
      action of hSLUG in human cells.

PMID- 17194446
TI  - Epitope mapping of human aromatic L-amino acid decarboxylase.
AB  - Autoimmune polyendocrine syndrome type I (APS I) is a rare hereditary condition
      considered a model disease for organ specific autoimmunity. A wide range of
      autoantibodies targeting antigens present in the affected organs have been
      identified. Autoantibodies against aromatic L-amino acid decarboxylase (AADC) are
      present in about 50% of APS I patients. In order to increase our understanding of
      autoantibody specificity in APS I, the aim of the present study was to localize
      target regions on AADC recognized by sera from APS I patients. Using several
      complementing strategies, we have shown that autoantibodies against AADC mainly
      recognize conformational epitopes. The major antigenic determinants were detected
      N-terminally to amino acid residue 237. Replacement of amino acids 227-230 (ERDK)
      with alanine residues reduced the reactivity towards AADC by >80% in all patient
      sera tested, suggesting that amino acids 227-230 are an important part of an
      immunodominant epitope.

PMID- 17194447
TI  - WNK1 and WNK4 modulate CFTR activity.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-gated
      chloride channel. WNK kinases are widely expressed modulators of ion transport.
      WNK1 and WNK4, two WNK kinases that are mutated in familial hyperkalemic
      hypertension (FHHt), are co-expressed with CFTR in several organs, raising the
      possibility that WNK kinases might alter CFTR activity in vivo or that CFTR could
      be involved in the pathogenesis of FHHt. Here, we report that WNK1 co-localizes
      with CFTR protein in pulmonary epithelial cells. Co-expression of WNK1 or WNK4
      with CFTR in Xenopus laevis oocytes suppresses chloride channel activity. The
      effect of WNK4 is dose dependent and occurs, at least in part, by reducing CFTR
      protein abundance at the plasma membrane. This effect is independent of WNK4
      kinase activity. In contrast, the effect of WNK1 on CFTR activity requires intact
      WNK1 kinase activity. Moreover WNK1 and WNK4 exhibit additive CFTR inhibition.
      Previous reports suggest that patients with FHHt exhibit mild changes in nasal
      potential difference that resemble the more severe changes that occur in cystic
      fibrosis. We report that the FHHt-causing mutant WNK4 Q562E is a more potent
      inhibitor of CFTR activity than is the wild-type WNK4. Taken together, these
      results suggest that WNK1 and WNK4 may modulate CFTR activity; they further
      suggest that WNK kinases may be potential therapeutic targets for cystic
      fibrosis.

PMID- 17194448
TI  - Detection of pre-neoplastic and neoplastic prostate disease by MALDI profiling of
      urine.
AB  - The heterogeneous progression to the development of prostate cancer (PCa) has
      precluded effective early detection screens. Existing prostate cancer screening
      paradigms have relatively poor specificity for cancer relative to other prostate
      diseases, commonly benign prostatic hyperplasia (BPH). A method for
      discrimination of BPH, HGPIN, and PCa urine proteome was developed through
      testing 407 patient samples using matrix assisted laser desorption-mass
      spectrometry time of flight (MALDI-TOF). Urine samples were adsorbed to reverse
      phase resin, washed, and the eluant spotted directly for MALDI-TOF analysis of
      peptides. The processing resolved over 130 verifiable signals of a mass range of
      1000-5000 m/z to suggest 71.2% specificity and 67.4% sensitivity in
      discriminating PCa vs. BPH. Comparing BPH and HGPIN resulted in 73.6% specificity
      and 69.2% sensitivity. Comparing PCa and HGPIN resulted in 80.8% specificity and
      81.0% sensitivity. The high throughput, low-cost assay method developed is
      amenable for large patient numbers required for supporting biomarker
      identification.

PMID- 17194449
TI  - GABPalpha regulates Oct-3/4 expression in mouse embryonic stem cells.
AB  - Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass
      of blastocysts, and transcription factors Oct-3/4, Nanog, Sox2, and STAT3, are
      essential for their self-renewal. In this study, we searched for molecules
      downstream of STAT3 in ES cells. Using DNA chip analysis, we obtained GA-repeat
      binding protein (GABP) alpha. Expression of GABPalpha was restricted to
      undifferentiated ES cells and controlled by STAT3. We found that the expression
      level of Oct-3/4 is reduced by knockdown of GABPalpha. On the other hand,
      GABPalpha-overexpressing ES cells maintained the expression level of Oct-3/4 even
      in the absence of LIF. Moreover, the induction of Oct-3/4 repressors Cdx-2, Coup
      tf1, and GCNF was stimulated by GABPalpha knockdown. These data suggest that
      GABPalpha upregulates the expression of Oct-3/4 via downregulation of Oct-3/4
      repressors.

PMID- 17194450
TI  - Xenopus Suppressor of Hairless 2 is involved in the cell fate decision during
      gastrulation through the transcriptional regulation of Xoct25/91.
AB  - We have previously indicated that Xenopus Suppressor of Hairless 2, XSu(H)2, is
      involved in the morphogenesis of gastrula embryos in a different manner from the
      XESR-1-mediated Notch signaling pathway. To address the downstream factors of
      XSu(H)2, we investigated the effect of XSu(H)2 on XenopusPOU-V genes, Xoct25 and
      Xoct91. Knockdown of XSu(H)2 caused the downregulation of Xoct25, Xoct91 and
      Xbrachyury. Dominant-negative Xoct25 caused the delay of blastopore closure with
      a decrease of Xbrachyury expression. Overexpression of Xoct25 or Xoct91 could
      rescue the decrease of Xbrachyury expression caused by XSu(H)2 depletion.
      XSu(H)2EnR inhibited Xoct25 and Xoct91 expressions in CHX-treated animal caps.
      Promoter analysis of the Xoct25 showed that the upstream region of Xoct25
      contains the prospective Su(H) binding motif, which is essential for the
      transcription of Xoct25. These results suggest that XSu(H)2 is engaged in the
      cell fate decision during gastrulation through the gene expression of the
      Xoct25/91-mediated pathway.

PMID- 17194451
TI  - Role of a cysteine residue in the active site of ERK and the MAPKK family.
AB  - Kinases of mitogen-activated protein kinase (MAPK) cascades, including
      extracellular signal-regulated protein kinase (ERK), represent likely targets for
      pharmacological intervention in proliferative diseases. Here, we report that
      FR148083 inhibits ERK2 enzyme activity and TGFbeta-induced AP-1-dependent
      luciferase expression with respective IC50 values of 0.08 and 0.05 microM.
      FR265083 (1'-2' dihydro form) and FR263574 (1'-2' and 7'-8' tetrahydro form)
      exhibited 5.5-fold less and no activity, respectively, indicating that both the
      alpha,beta-unsaturated ketone and the conformation of the lactone ring contribute
      to this inhibitory activity. The X-ray crystal structure of the ERK2/FR148083
      complex revealed that the compound binds to the ATP binding site of ERK2,
      involving a covalent bond to Sgamma of ERK2 Cys166, hydrogen bonds with the
      backbone NH of Met108, Nzeta of Lys114, backbone C=O of Ser153, Ndelta2 of
      Asn154, and hydrophobic interactions with the side chains of Ile31, Val39, Ala52,
      and Leu156. The covalent bond motif in the ERK2/FR148083 complex assures that the
      inhibitor has high activity for ERK2 and no activity for other MAPKs such as JNK1
      and p38MAPKalpha/beta/gamma/delta which have leucine residues at the site
      corresponding to Cys166 in ERK2. On the other hand, MEK1 and MKK7, kinases of the
      MAPKK family which also can be inhibited by FR148083, contain a cysteine residue
      corresponding to Cys166 of ERK2. The covalent binding to the common cysteine
      residue in the ATP-binding site is therefore likely to play a crucial role in the
      inhibitory activity for these MAP kinases. These findings on the molecular
      recognition mechanisms of FR148083 for kinases with Cys166 should provide a novel
      strategy for the pharmacological intervention of MAPK cascades.

PMID- 17194452
TI  - HNF-1alpha participates in glucose regulation of sucrase-isomaltase gene
      expression in epithelial intestinal cells.
AB  - Sucrase-isomaltase (SI) gene expression is negatively regulated by glucose, but
      its molecular mechanism is not completely clear. The purpose of this study is to
      investigate whether HNF-1alpha and HNF-1beta contribute to glucose regulation of
      SI gene expression. To explore this question, we examined the association of gene
      expressions between SI and HNF-1alpha and HNF-1beta in Caco-2 cells cultured in
      medium containing 2.0 and 16.7 mM glucose. We found that gene expression of HNF
      1alpha but not HNF-1beta exhibits a positive correlation with that of SI
      regulated by glucose. Moreover, to elucidate whether glucose regulation of SI
      gene expression is changed when HNF-1alpha and HNF-1beta are inhibited, we
      produced three stable cell lines, in which dominant-negative mutant HNF
      1alphaT539fsdelC, mutant HNF-1betaR177X, and empty vector (as a control),
      respectively, were stably expressed. We found that the glucose regulation of SI
      gene expression was significantly attenuated in HNF-1alphaT539fsdelC cells, but
      it was well maintained in empty vector and HNF-1betaR177X cells. These results
      suggest that HNF-1alpha participates in glucose regulation of SI gene expression.

PMID- 17194453
TI  - Tissue type-specific modulation of ER transcriptional activity by NFAT3.
AB  - NFAT3 belongs to the NFAT family of transcription factors playing important roles
      in the development of several organ systems and was found to act as a
      transcriptional coactivator of estrogen receptors (ERalpha and ERbeta) in breast
      cancer cells. Since some cofactors of transcription factors show cell or tissue
      type-specific effects on transcriptional regulation, we investigated the effect
      of NFAT3 on the transcriptional activity of ERs in different cell lines
      originated from kidney. Surprisingly, overexpression of NFAT3 in these cell types
      decreased dose-dependently both ERalpha and ERbeta transcriptional activities in
      a ligand-independent manner. Knockdown of endogenous NFAT3 using NFAT3 small
      interfering RNA (siRNA) increased ER transcriptional activities. NFAT3 deletion
      mutants lacking the ER-binding sites completely abolished the NFAT3 repression of
      ERalpha and ERbeta transcriptional activities. Replacement of Ser168 and Ser170,
      the amino acid residues on which NFAT3 can be phosphorylated, with Ala did not
      change the ability of NFAT3 to inhibit the transcriptional activity of ERalpha
      and ERbeta. Taken together, these results demonstrate that NFAT3 is a new kind of
      cofactor that displays dual transcription modulation mode dependent on tissue
      types.

PMID- 17194454
TI  - Integrin-linked kinase is involved in matrix-induced hepatocyte differentiation.
AB  - Hepatocytes have restricted proliferative capacity in culture and when cultured
      without matrix, lose the hepatocyte-specific gene expression and characteristic
      cellular micro-architecture. Overlay of matrix-preparations on de-differentiated
      hepatocytes restores differentiation. Integrin-linked kinase (ILK) is a cell
      matrix-adhesion protein crucial in fundamental processes such as differentiation
      and survival. In this study, we investigated the role of ILK, and its binding
      partners PINCH, alpha-parvin, and Mig-2 in matrix-induced hepatocyte
      differentiation. We report here that ILK is present in the liver and localizes at
      cell-matrix adhesions of cultured hepatocytes. We also show that ILK, PINCH,
      alpha-parvin, and Mig-2 expression level is dramatically reduced in the re
      differentiated hepatocytes. Interestingly, hepatocytes lacking ILK undergo matrix
      induced differentiation but their differentiation is incomplete, as judged by
      monitoring cell morphology and production of albumin. Our results show that ILK
      and cell-matrix adhesion proteins play an important role in the process of matrix
      induced hepatocyte differentiation.

PMID- 17194455
TI  - Adoptive transfer of dying cells causes bystander-induced apoptosis.
AB  - The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death
      from several noxious stimuli. Intriguingly, Bcl-2 overexpression in one cell type
      has been reported to protect against cell death in neighboring non-Bcl-2
      overexpressing cell types. The mechanism of this "trans" protection has been
      speculated to be secondary to the release of a cytoprotective factor by Bcl-2
      overexpressing cells. We employed a series of adoptive transfer experiments in
      which lymphocytes that overexpress Bcl-2 were administered to either wild type
      mice or mice lacking mature T and B cells (Rag-1-/-) to detect the presence or
      absence of the putative protective factor. We were unable to demonstrate "trans"
      protection. However, adoptive transfer of apoptotic or necrotic cells exacerbated
      the degree of apoptotic death in neighboring non-Bcl-2 overexpressing cells (p <
      or= 0.05). Therefore, this data suggests that dying cells emit signals triggering
      cell death in neighboring non-Bcl-2 overexpressing cells, i.e., a "trans"
      destructive effect.

PMID- 17194456
TI  - Sodium nitroprusside decreased leukotriene C4 generation by inhibiting
      leukotriene C4 synthase expression and activity in hepatic ischemia-reperfusion
      injured rats.
AB  - The effects of NO on LTC4 generation during hepatic ischemia-reperfusion (I/R)
      are largely unclear. Sprague-Dawley rats were divided into control, I/R and
      sodium nitroprusside (SNP, 2.5, 5 and 10 microg/kg/min)+I/R groups. Liver was
      subjected to I/R injury, saline or SNP administered intravenously. The protein
      expressions of LTC4 synthesis enzymes including LTC4 synthase (LTC4S), microsomal
      glutathione-S-transferase (mGST)2 and mGST3 were detected with immunoblotting,
      the LTC4 synthesis enzymes' activities and LTC4 content were measured by RP-HPLC,
      the mRNA expressions of inducible nitric oxide synthase (iNOS) and endogenous
      nitric oxide synthase (eNOS) in liver were measured by RT-PCR. Tissue injuries
      were assessed by serum ALT and AST and histological changes. Serum NO(2)(-) and
      liver tissue GSH were also examined. Compared with I/R group, SNP markedly
      decreased LTC4 content, LTC4S protein and iNOS mRNA levels, and the LTC4
      synthesis enzymes' activities (P<0.05), but significantly enhanced eNOS mRNA
      expression in liver (P<0.05). The decline in serum ALT, AST and NO(2)(-) levels
      (P<0.05) together with hepatic GSH elevation (P<0.05) in SNP+I/R groups were also
      observed. LTC4S expression in hepatocytes and sinusoidal endothelial cells in
      SNP+I/R groups was lower than that in I/R group. But no significant differences
      in the protein expressions of mGST3 and mGST2 existed between control, I/R and
      SNP+I/R groups (P>0.05). These results demonstrated that the decline in LTC4
      production by SNP treatment during hepatic I/R could be partially resulted from
      SNP down-regulating the protein expression of LTC4S rather than mGST2 or mGST3
      and its inhibiting the LTC4 synthesis enzymes' activities.

PMID- 17194457
TI  - Behavioral effects of pubertal anabolic androgenic steroid exposure in male rats
      with low serotonin.
AB  - The goal of this study was to assess the interactive effects of chronic anabolic
      androgenic steroid (AAS) exposure and brain serotonin (5-hydroxytryptamine, 5-HT)
      depletion on behavior of pubertal male rats. Serotonin was depleted beginning on
      postnatal day 26 with parachlorophenylalanine (PCPA 100 mg/kg, every other day);
      controls received saline. At puberty (P40), half the PCPA-treated rats and half
      the saline-treated rats began treatment with testosterone (T, 5 mg/kg, 5
      days/week). Behavioral measures included locomotion, irritability, copulation,
      partner preference, and aggression. Animals were tested for aggression in their
      home cage, both with and without physical provocation (mild tail pinch). Brain
      levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were
      determined using HPLC. PCPA significantly and substantially depleted 5-HT and 5
      HIAA in all brain regions examined. Chronic T treatment significantly decreased 5
      HT and 5-HIAA in certain brain areas, but to a much lesser extent than PCPA.
      Chronic exposure to PCPA alone significantly decreased locomotor activity and
      increased irritability but had no effect on sexual behavior, partner preference,
      or aggression. T alone had no effect on locomotion, irritability, or sexual
      behavior but increased partner preference and aggression. The most striking
      effect of combining T+PCPA was a significant increase in attack frequency as well
      as a significant decrease in the latency to attack, particularly following
      physical provocation. Based on these data, it can be speculated that pubertal AAS
      users with low central 5-HT may be especially prone to exhibit aggressive
      behavior.

PMID- 17194458
TI  - Evaluation of the antioxidant and cytotoxic activity of arzanol, a prenylated
      alpha-pyrone-phloroglucinol etherodimer from Helichrysum italicum
      subsp.microphyllum.
AB  - Various phenolics and (mero)terpenoids from Helichrysum italicum subsp.
      microphyllum, a plant endemic to Sardinia, were investigated for their capacity
      to inhibit non-enzymatic lipid peroxidation. These compounds were studied in
      simple in vitro systems, under conditions of autoxidation and of iron (EDTA)
      mediated oxidation of linoleic acid at 37 degrees C. Arzanol, a pyrone
      phloroglucinol etherodimer, and helipyrone, a dimeric pyrone, showed antioxidant
      activity, and could protect linoleic acid against free radical attack in assays
      of autoxidation and EDTA-mediated oxidation. Methylarzanol, as well as the
      sesquiterpene alcohol rosifoliol, showed a decreased, but still significant,
      protective effect against linoleic acid oxidation. Arzanol and helipyrone were
      also tested in an assay of thermal (140 degrees C) autoxidation of cholesterol,
      where arzanol showed significant antioxidant activity. The cytotoxicity of
      arzanol was further evaluated in VERO cells, a line of fibroblasts derived from
      monkey kidney. Arzanol, at non-cytotoxic concentrations, showed a strong
      inhibition of TBH-induced oxidative stress in VERO cells. The results of the
      present work suggest that the natural compound arzanol exerts useful antioxidant
      properties in different in vitro systems of lipid peroxidation.

PMID- 17194459
TI  - Oxidized LDL specifically promotes the initiation of monocyte invasion during
      transendothelial migration with upregulated PECAM-1 and downregulated VE-cadherin
      on endothelial junctions.
AB  - It is poorly understood how oxidized LDL (oxLDL) promotes monocyte dynamics in
      transendothelial migration (TEM) in atherogenesis. We developed an in vitro 3D
      live-single cell TEM assay system with subendothelial oxLDL embedded in ultra
      thin collagen gels, mimicking subendothelial oxLDL accumulation in vivo. With
      dividing monocyte dynamics into three stages (1: adhesion on endothelium, 2:
      invasion and 3: complete transmigration below endothelium), we analyzed the stage
      transition dynamics of individual living human monocytes. OxLDL did not enhance
      initial monocyte adhesion to endothelium (stage 1), but it specifically primed
      adherent monocytes to start invasion (stage 1-->2). Once invasion started, it had
      no effect thereafter on monocyte stage transition (stage 2-->3). OxLDL
      upregulated PECAM-1 and downregulated VE-cadherin on endothelial junctions
      without monocyte addition, both of which could promote monocyte entry by enhanced
      homophilic binding to monocyte PECAM-1, and by disrupted junctional barrier,
      respectively. Meanwhile, monocyte speed at neither locomotion on endothelium
      (stage 1) nor subendothelial migration (stage 3) was altered by oxLDL. These data
      indicate that before monocyte adhesion, endothelial junctions changed their
      conformation to more monocyte-acceptable state in response to oxLDL, resulting
      the stage-specific promotion of monocyte TEM (stage 1-->2; initiation of
      invasion) with no enhancement of its initial adhesion or migration speed.

PMID- 17194460
TI  - Familial defective apolipoprotein B-100 in Slovakia: are differences in
      prevalence of familial defective apolipoprotein B-100 explained by ethnicity?
AB  - The objective of this study was to examine frequency of familial defective apo-B
      100 (FDB, R3500Q mutation) in probands with the phenotype of familial
      hypercholesterolemia (FH) and in the general population of 40-year-old subjects
      in Slovakia and to characterize their lipid and clinical criteria and to compare
      the frequency of FDB with other populations. We identified 35 patients with FDB
      among 362 probands with clinical diagnosis of FH and two cases of FDB in the 40
      year-old cohort of 2323 subjects from general Slovak population. Probands with
      FDB differed from those with FH only in plasma triglyceride concentrations
      (1.84+/-1.4 mmol/l versus 1.45+/-0.98 mmol/l, respectively, p<0.01). Evaluation
      of personal history of premature atherosclerosis did not show any differences
      (11.4% in FDB versus 20% in FH, p<0.16). The FDB patients had similar
      manifestation of xanthomatosis as the FH patients (17.1% versus 8.25%, p<0.25).
      The frequency of FDB of 9.7% found in the FH patients is among the highest of
      those reported to date. The frequency of R3500Q mutation of 0.09% found in Slovak
      40-year-old subjects did not differ significantly from published population
      molecular data. Our comparison of estimated FDB frequencies with those which were
      found by DNA analysis demonstrated that estimated frequencies were not only wider
      in range, but also significantly higher than those which were assessed by the
      analysis. The definitive answer to the prevalence of FDB and its biochemical and
      clinical characteristics requires screening of unbiased samples of the general
      population from different ethnic groups based on molecular genetic methods.

PMID- 17194461
TI  - The role of c-jun in PDTC-sensitive flow-dependent restenosis after angioplasty
      and stenting.
AB  - Restenosis after balloon angioplasty and stenting is exacerbated by low flow.
      Flow-dependent restenosis after angioplasty but not stenting is prevented by the
      antioxidant pyrrolidine dithiocarbamate (PDTC). c-jun may play a role in these
      events as AP-1 activity is both flow and redox sensitive. Carotid arteries of
      cholesterol fed rabbits underwent stenting or balloon injury in the presence of
      low or normal flow. c-jun mRNA expression was enhanced by low flow and injury
      (stent>balloon) and inhibited by the antioxidant PDTC irrespective of the injury
      type. The effect of locally delivered DZ13 (a DNAzyme specific for c-jun) or
      scrambled DZ13 (inactive DNAzyme) was assessed by histomorphometry at 28 days.
      Low flow significantly increased intimal hyperplasia in B and S relative to
      normal flow (P<0.05). The active DNAzyme DZ13 markedly reduced intimal
      hyperplasia (P<0.001) and increased lumen size (P<0.05) in balloon-injured but
      not in stented segments, and abrogated the effect of low flow on restenosis after
      angioplasty, similar to the morphological effects of PDTC. We conclude that c-jun
      expression is enhanced by low flow and by injury (stent>balloon) and markedly
      attenuated by PDTC, and that c-jun is an important mediator of flow-dependent
      restenosis in balloon-injured but not stented vessels.

PMID- 17194462
TI  - Resin characterization by electro-acoustic measurements.
AB  - The electro-acoustic effects, namely the ion vibration potential (IVP) and the
      colloidal vibration current (CVI), colloidal vibration potential (CVP) first
      described by P. Debye [P. Debye, J. Chem. Phys. 1 (1933) 13], are a result of
      charge separation of bound or free ions at different degrees by ultrasonic waves.
      Today commercial instruments are available to investigate liquid homogeneous and
      heterogeneous systems. In the present paper the application of this technique for
      the characterization of salts, protein solutions and resins for biochromatography
      is shown and valuable information about resins can be derived in a short time.
      Various resins were investigated with the following results: (1) the CVI
      magnitude is dependent of several parameters (such as particle size distribution,
      volume fraction, density difference); (2) the CVI is influenced by the surface
      modification of the resins. Polymeric modifications decrease the value of CVI.
      The CVI is generally lower for high capacity resins; (3) the measurement of the
      electro-acoustic effects can be used to detect small changes in resins. The CVI
      is dependent of the amount of adsorbed protein in "native" and denatured state.

PMID- 17194463
TI  - Dynamic evolution of the CYP2ABFGST gene cluster in primates.
AB  - We have annotated and analyzed sequences from the CYP2ABFGST gene cluster for the
      chimpanzee and the Rhesus macaque, and compared them in detail to the complete
      map of the syntenic human cluster. While the macaque cluster has accumulated
      substantial differences in gene number and organization relative to the other two
      species, the chimpanzee cluster has remained surprisingly similar to the human
      cluster, given the evolutionary volatility of this gene family. The comparison
      will allow us to further refine our model of the evolution of this gene family in
      mammals.

PMID- 17194464
TI  - Isolation and characterization of rufoxin, a novel protein exhibiting
      neurotoxicity from venom of the psammophiine, Rhamphiophis oxyrhynchus (Rufous
      beaked snake).
AB  - Colubrid snake venoms potentially represent a vast source of novel biological
      actives and structural motifs owing to their diverse phylogeny. The present study
      describes the identification of rufoxin, a neurotoxin from the venom of
      Rhamphiophis oxyrhynchus (Rufous beaked snake) which is a member of the African
      colubrid lineage, the psammophiines. Rufoxin (1 microM) displayed reversible post
      synaptic neurotoxic activity as evidenced by significant inhibition of indirect
      twitches and responses to exogenous nicotinic agonists in the chick biventer
      cervicis nerve-muscle preparation. Rufoxin (0.1-1.0 microM) also caused a
      rightward parallel shift of cumulative concentration-response curves to carbachol
      (CCh; 0.6-80 microM) without a significant depression of the maximum response,
      suggestive of classical competitive antagonism at the skeletal muscle nicotinic
      receptor. Rufoxin lacks NH(2)-terminal sequence homology to previously identified
      snake venom toxins. This work indicates a wider distribution of neurotoxins
      across the advanced snake superfamily than previously described.

PMID- 17194465
TI  - Effects of age and mild cognitive impairment on direct and indirect access to
      arithmetic knowledge.
AB  - The present study aimed at investigating age-related changes and mild cognitive
      impairment (MCI) related effects in simple arithmetic. To pursue this goal, MCI
      patients, healthy old adults and young adults performed three computerised tasks.
      The production (e.g., 3 x 4=?) and the verification task (3 x 4 12?) evaluated
      direct access to multiplication knowledge, the number-matching task (3 x 4 34?,
      'do 3 x 4 and 34 have the same digits?') tested indirect access. In verification
      and number-matching, interference from related distractors (e.g., 3 x 4 followed
      by 16) relative to unrelated distractors (17) reflects access to stored fact
      representations as well as efficiency of inhibition processes. Results indicated
      that, compared to young adults, MCI and healthy old adults were slower in
      responding across tasks. In production and verification, analyses of individual
      latency regression slopes and intercepts suggested that these age effects were
      related to differences at peripheral processing stages (e.g., encoding) rather
      than at the central (arithmetic retrieval) stage. Differences between MCI and
      healthy elderly emerged only in the number-matching task. While in verification
      effects were comparable between groups, in number-matching MCI patients were more
      susceptible to interference from irrelevant information than healthy old
      participants. Overall, the present findings indicate that aging has a general
      effect on peripheral processing speed, but not on arithmetic memory retrieval.
      Parietal cortico-subcortical circuits mediating arithmetic fact retrieval
      (Dehaene, S., & Cohen, L. (1995). Towards an anatomical and functional model of
      number processing. Mathematical Cognition, 1, 83-120; Dehaene, S., & Cohen, L.
      (1997). Cerebral pathways for calculation: Double dissociation between rote
      verbal and quantitative knowledge of arithmetic. Cortex, 33, 219-250) thus seem
      to be preserved in normal aging and MCI. In contrast, MCI patients show enhanced
      interference in number-matching. This task-specific lack of inhibition may point
      to dysfunctional frontal cortico-subcortical networks in MCI.

PMID- 17194466
TI  - The neural basis of conditional reasoning: an event-related potential study.
AB  - The spatiotemporal analysis of brain activation during the execution of
      conditional reasoning tasks (the four inference forms: Modus Ponens (MP), Modus
      Tollens (MT), affirming the consequent (AC), and denying the antecedent (DA)) and
      one baseline task (BS) was performed in 12 normal young adult participants using
      high-density event-related brain potentials (ERPs). Results showed that the early
      components elicited by the five task types were not significantly different.
      Reasoning tasks elicited a more negative EPR deflection (N600) than did the BS
      task in the time window of 500-700 ms after onset of the minor premise. Dipole
      source analysis of the difference wave (MP-BS) suggested that a generator
      localized in the left anterior cingulate cortex (BA 24) was involved in the
      activation and the application of the inference rules. ERP components of the five
      tasks were similar in the subsequent time period between 700 and 1700 ms.
      Following that period, a greater negativity in the reasoning tasks, in comparison
      to the BS task, developed between 1700 and 2000 ms poststimulus over the left
      fronto-central scalp regions. A generator of this effect was located in the right
      anterior cingulate cortex (BA 24) and was possibly related to cognitive control.
      The results indicate that the cingulate cortex was activated by conditional
      reasoning tasks with purely abstract materials and support the view that human
      reasoning is not a unified phenomenon but is content-sensitive.

PMID- 17194467
TI  - Mild and selective deprotection method of acetylated steroids and diterpenes by
      dibutyltin oxide.
AB  - Dibutyltin oxide (DBTO) was first utilized for the deacetylation of steroid and
      diterpene esters. The results showed the deprotection of acetylated steroids and
      diterpenes separately with moderate catalysis dibutyltin oxide in methanol
      selectively removed part acetyl groups of these substrates, whereas several
      functional groups of the steroids and diterpenes were retained and neither
      isomerization nor degradation of these substrates was observed. It seems that the
      acetyl groups with lower steric hindrance or near carbonyl, alkoxy, or hydroxyl
      groups can be cleaved by the reaction, whereas the acetyl groups with higher
      steric hindrance or without carbonyl, alkoxy, or hydroxyl groups neighboring were
      retained under the same conditions. One of the interesting results obtained was
      the selective hydrolysis of the 3beta-O-acetyl group in the presence of the 6beta
      group in 3beta,6beta-Di-O-acetyl-5alpha-hydroxypregn-16-en-20-one. This allows
      for subsequent introduction of one unit at C-3 and the other unit at C-6. This
      procedure is useful for the synthesis of a series of closely related isomers of
      3beta,5alpha,6beta-trihydroxypregn-16-en-20-one and other widespread
      polyhydroxysteroids in marine organisms and some terrestrial species.

PMID- 17194468
TI  - Chimpanzee tool technology in the Goualougo Triangle, Republic of Congo.
AB  - With the exception of humans, chimpanzees show the most diverse and complex tool
      using repertoires of all extant species. Specific tool repertoires differ between
      wild chimpanzee populations, but no apparent genetic or environmental factors
      have emerged as definitive forces shaping variation between populations. However,
      identification of such patterns has likely been hindered by a lack of information
      from chimpanzee taxa residing in central Africa. We report our observations of
      the technological system of chimpanzees in the Goualougo Triangle, located in the
      Republic of Congo, which is the first study to compile a complete tool repertoire
      from the Lower Guinean subspecies of chimpanzee (Pan troglodytes troglodytes).
      Between 1999 and 2006, we documented the tool use of chimpanzees by direct
      observations, remote video monitoring, and collections of tool assemblages. We
      observed 22 different types of tool behavior, almost half of which were habitual
      (shown repeatedly by several individuals) or customary (shown by most members of
      at least one age-sex class). Several behaviors considered universals among
      chimpanzees were confirmed in this population, but we also report the first
      observations of known individuals using tools to perforate termite nests,
      puncture termite nests, pound for honey, and use leafy twigs for rain cover. Tool
      behavior in this chimpanzee population ranged from simple tasks to hierarchical
      sequences. We report three different tool sets and a high degree of tool-material
      selectivity for particular tasks, which are otherwise rare in wild chimpanzees.
      Chimpanzees in the Goualougo Triangle are shown to have one of the largest and
      most complex tool repertoires reported in wild chimpanzee populations. We
      highlight new insights from this chimpanzee population to our understanding of
      ape technological systems and evolutionary models of tool-using behavior.

PMID- 17194469
TI  - Reliability and predictive validity of the Asthma Control Test administered by
      telephone calls using speech recognition technology.
AB  - BACKGROUND: The Asthma Control Test (ACT) has been validated in a paper and
      pencil version but has not been validated for use by telephone. OBJECTIVE: The
      purpose of this study was to provide validation data for the ACT administered by
      interactive telephone calls using speech recognition technology. METHODS: The ACT
      was administered to patients who confirmed a diagnosis of physician-diagnosed
      asthma, and information regarding race/ethnicity, smoking, and asthma course was
      also obtained during the call. Asthma emergency department visits,
      hospitalizations, and oral corticosteroid and beta-agonist canister dispensings
      were assessed for the 12 months after the date of each patient's call. Internal
      consistency reliability and predictive validity were assessed. RESULTS: Asthma
      Control Test scores (higher indicates better control) were completed by 2244
      patients and were inversely related to black or Hispanic race/ethnicity and
      smoking. Reliability was 0.83. ACT scores were significantly related to emergency
      hospital care and oral corticosteroid and beta-agonist dispensings over the
      period of the subsequent 6 and 12 months. After adjusting for demographic
      characteristics, a score < or = 15 was associated significantly with an increased
      12-month risk of emergency hospital care (odds ratio [OR], 2.5), oral
      corticosteroid dispensings (OR, 2.6) and dispensing of more than 6 beta-agonist
      canisters (OR, 6.8) compared with a score > or = 20. CONCLUSION: These data
      support the reliability and predictive validity of the ACT administered by
      interactive telephone calls using speech recognition technology. CLINICAL
      IMPLICATIONS: The ACT can be used for outreach or follow-up by means of
      interactive telephone calls using speech recognition technology.

PMID- 17194471
TI  - Severe refractory atopic dermatitis in adults is highly atopic.

PMID- 17194472
TI  - The impact of modifying alumina air abrasion parameters on the fracture strength
      of a porcelain laminate restorative material.
AB  - OBJECTIVES: The modification of the "fit" surface of porcelain laminate veneer
      restorations in order to improve adhesion prior to cementation is often
      indiscriminate. As a consequence, the surface flaw distribution which is
      implicated in the probability of failure of the restoration is likely to be
      dramatically modified. The purpose of the current study was to examine the impact
      of different air abrasion surface treatments on the bi-axial flexure strength and
      surface roughness of a porcelain restorative material. METHODS: Sets of 30
      Vitadur-Alpha dentin porcelain discs (15 mm diameter, 0.9 mm thickness) were
      alumina abraded with three different grades of alumina particle (25, 50 and 110
      microm), utilizing two different air stream pressures (35 and 70 psi) and two
      distinct angles of incidence of particle delivery (45 degrees and 90 degrees ).
      Mean bi-axial flexure strengths, standard deviations, the associated Weibull
      moduli (m) and characteristic stress were determined using bi-axial flexure (ball
      on ring). RESULTS: A univariate general linear analysis of means revealed a
      significant difference between the mean bi-axial flexure strength values of the
      control group and those of groups subjected to alumina particle air abrasion.
      Further significance (P<0.05) was discovered with the impact of alumina particle
      size and the interaction between particle size and angle of incidence of particle
      delivery. The reliability of the fracture strength data generally improved when
      50 microm alumina particles were used whereas discontinuities existed at lower
      strength values when 25 and 110 microm alumina particles were employed.
      CONCLUSIONS: Alumina particle air abrasion has a significant degradative effect
      on the bi-axial flexure strength of the porcelain disc-shaped specimens.
      Variation of alumina size, delivery pressure and angle of particle delivery all
      impacted on the degree of strength reduction and the shape of the survival
      probability distributions. It is suggested that alumina particle air abrasion
      acts to remove/modify the initial flaw distribution replacing it with flaws of
      differing geometry and stability. The premature failure of porcelain laminate
      restorations may be markedly influenced by alumina particle air abrasion
      depending upon the size and distribution of the crystalline phase present in
      different dentine porcelains materials used in construction of the restoration.

PMID- 17194473
TI  - Two-dimensional gradient platforms for rapid assessment of dental polymers: a
      chemical, mechanical and biological evaluation.
AB  - OBJECTIVES: The increased usage of composite dental restorations underscores the
      need for continued improvements in material properties. Well-controlled sample
      fabrication and reproducible methods to quantify and compare material properties
      will accelerate material design and optimization. Our objectives were to
      fabricate samples encompassing a range of processing parameters and develop
      techniques that systematically quantify multiple properties of these samples,
      thus reducing sample-to-sample variation while concurrently testing numerous
      processing conditions. METHODS: Gradient samples were prepared to evaluate the
      effects of composition and irradiation time. Comonomer ratio of 2,2-bis[p-2'
      hydroxy-3'-methacryloxypropoxy]-phenyl]propane (BisGMA) and triethylene glycol
      dimethacrylate (TEGDMA) was varied discretely, and irradiation time was varied
      continuously across each composition. Degree of conversion was measured using
      infrared spectroscopy, mechanical properties were evaluated using
      nanoindentation, and cell viability and density were quantified using
      fluorescence microscopy. RESULTS: Higher BisGMA contents increased elastic moduli
      while higher TEGDMA contents increased conversions. Cell response depended only
      on irradiation time and not composition, with conversions of at least 52% and 60%
      required for unaffected viability and cell density, respectively. A single
      composition-irradiation combination to achieve all of the 'best' properties
      (highest conversion, highest elastic modulus, lack of cytotoxicity) was not
      identified, illustrating the necessity of testing all combinations for multiple
      relevant properties. SIGNIFICANCE: Simultaneously screening composition and
      conversion increased the experimental throughput and allowed for the
      quantification of chemical, mechanical, and biological properties in a
      controlled, reproducible fashion. This 2D gradient approach is useful for
      optimizing compositions and processing parameters to achieve the desired
      combination of properties.

PMID- 17194474
TI  - Effects of growth factors on dental pulp cell sensitivity to amalgam toxicity.
AB  - OBJECTIVES: The objective was to determine the effects of growth factor treatment
      on dental pulp cell sensitivity to toxicity. METHODS: The toxicity of zinc
      containing and zinc-free dental amalgam was tested on four types of cells; glia,
      neurons, embryonic stem cells, and dental pulp cells. The effects of six
      different growth factors were tested on dental pulp cell sensitivity to amalgam
      toxicity. RESULTS: Zinc-containing amalgam was highly toxic to all cell types
      tested. Zinc-free amalgam was less toxic, but it was most toxic to dental pulp
      cells. Exposure of dental pulp cells to the growth factors IGF-I or BMP-7 had no
      effect on their morphology or rate of cell division, and did not alter their
      sensitivity to zinc-free amalgam toxicity. Exposure to EGF, bFGF, or TGF-beta
      altered the morphology and decreased the rate of cell division, and the cells
      were no longer sensitive to zinc-free amalgam toxicity. Exposure to BMP-2 also
      altered the morphology and decreased the rate of cell division, but the cells
      remained sensitive to zinc-free amalgam toxicity. SIGNIFICANCE: The results
      indicate that untreated dental pulp cells are highly sensitive to amalgam
      toxicity, but that sensitivity can be decreased by exposure to certain growth
      factors. Therefore, for treatment of conditions in which pulp cells may come in
      contact with substances released from dental materials, such as pulp capping, the
      use of amalgam should be avoided unless the pulp cells are first treated with the
      proper growth factors.

PMID- 17194476
TI  - Gene polymorphisms associated with reduced hepatic expression of porcine mannan
      binding lectin C.
AB  - Previous studies showed that low expression of mannan-binding lectin C (MBL-C) in
      pigs was not due to single-nucleotide polymorphisms (SNPs) in the coding region
      of pig MBL2. In these studies, we compared the 5' flanking regions of porcine
      MBL1 (1907 bp) and MBL2 (1880 bp) in normal and diseased pigs with low or high
      hepatic expression of MBL2. Hepatic expression of MBL-C was very low in all pigs
      submitted for postmortem diagnosis. In various European pig breeds, a G(-1081)A
      substitution was linked to very low hepatic MBL-C expression, and was more
      frequent in diseased pigs. A C(-251)T substitution with less influence on MBL-C
      expression was more common in various breeds but was not associated with disease.
      MBL2 polymorphisms were associated with some disease groups and with the presence
      of some etiologic agents. These findings indicate that some promoter
      polymorphisms impair MBL-C expression in pigs and may increase their
      susceptibility to disease.

PMID- 17194475
TI  - Biofilm formation on surface characterized micro-implants for skeletal anchorage
      in orthodontics.
AB  - Micro-implants are increasingly popular in clinical orthodontics to effect
      skeletal anchorage. However, biofilm formation on their surfaces and subsequent
      infection of peri-implant tissues can result in either exfoliation or surgical
      removal of these devices. The present study aimed to assess biofilm formation on
      five commercially available, surface characterized micro-implant systems in
      vitro. The elemental surface compositions of as-received and autoclave-sterilized
      micro-implants were characterized by X-ray photoelectron spectroscopy. High
      carbon contamination was detected on the oxide surfaces, along with traces of
      inorganic elements (Ca, Cu, Cr, Pb, Zn, and P) which disappeared after Ar(+) ion
      sputtering. The mean surface roughnesses (R(a)) were around 182nm for titanium
      micro-implants, and 69nm for stainless steel micro-implants, as measured by
      atomic force microscopy. Scanning electron microscopy revealed different surface
      topographies between manufacturers, varying from typical machined grooves to
      structural defects like pores and pits. Overnight biofilms were grown on micro
      implant surfaces by immersion in pooled human whole saliva. Biofilms on micro
      implants treated with chlorhexidine and fluoride mouthrinses contained comparable
      numbers of viable organisms, but significantly less than did untreated micro
      implants. Comparison of different implant systems using multiple linear
      regression analysis indicated that biofilm formation was governed by roughness of
      the implant surface and the prevalence of carbon- and oxygen-rich components.

PMID- 17194477
TI  - Expression analysis of two Eomesodermin homologues in zebrafish lymphoid tissues
      and cells.
AB  - Eomesodermin (Eomes) is a T-box transcription factor that is involved in mesoderm
      formation in most vertebrates. Eomes is also expressed in CD8+ T cells and NK
      cells. No information is available on the role of Eomes in the immune system of
      lower vertebrates to date, although developmental studies on Eomes (Eomes1) have
      been performed in zebrafish. Here we report the identification of a second Eomes
      (Eomes2) in zebrafish and compare expression of the two Eomes genes in the immune
      system. Zebrafish Eomes1 and Eomes2, composed of 661 and 534 amino acids,
      respectively, share 49.3% amino acid identity in their coding regions and 88.7%
      amino acid identity in their T-box regions. Conserved synteny between regions of
      the human and zebrafish genomes, gene organization and phylogenetic analysis all
      indicate that the zebrafish Eomes2 gene is a homologue of mammalian Eomes, as
      previously found for zebrafish Eomes1. Eomes1 mRNA was found to be expressed in
      the gonad, body kidney, spleen and gill, while Eomes2 mRNA was not detected in
      any of these tissues. However, strong expression of both Eomes mRNAs was detected
      in the leukocytes from the spleen, followed by those from body kidney and
      peripheral blood, with expression of Eomes1 always stronger than that of Eomes2.
      RT-PCR analysis of body kidney cells sorted by FACS revealed that Eomes1 was
      expressed strongly in lymphocytes, weakly in blast cells, and was not expressed
      in granulocytes, while Eomes2 was expressed weakly in lymphocytes. These results
      suggest that both Eomes genes are involved in the zebrafish immune response,
      particularly in lymphocyte function as has been found in mammals.

PMID- 17194478
TI  - Effect of indocyanine green staining in peeling of internal limiting membrane for
      retinal detachment resulting from macular hole in myopic eyes.
AB  - PURPOSE: To investigate the effect of using indocyanine green (ICG) to stain the
      internal limiting membrane (ILM) during vitrectomy in eyes with retinal
      detachment resulting from macular hole (MHRD). DESIGN: Nonrandomized comparative
      trial. PARTICIPANTS: Thirty-two cases of MHRD. INTERVENTION: The medical records
      of the cases were reviewed retrospectively. During the initial vitrectomy, the
      ILM was peeled in 22 eyes with ICG (group A) and in 10 eyes without ICG (group
      B). MAIN OUTCOME MEASURES: Anatomic reattachment, visual acuity, and optical
      coherence tomography-determined macular hole closure were measured. RESULTS: The
      initial reattachment rate in group A (86%) was significantly higher than in group
      B (40%; P = 0.013, Fisher exact test). The postoperative visual acuity at 6
      months and the visual improvements at 6 and 12 months in eyes with an initial
      reattachment were not significantly different between the 2 groups (P = 0.123,
      Mann-Whitney rank-sum test; P = 0.17, t test; P = 0.237, t test). The
      postoperative visual acuity at 12 months with an initial reattachment in group A
      was significantly better than in group B (P = 0.039, t test). The macular hole
      closure rate with an initial reattachment was 6 of 17 eyes (35%) in group A and 0
      of 4 eyes (0%) in group B, and this difference was not significant (P = 0.281,
      Fisher exact test). CONCLUSIONS: These results show that ICG staining improves
      the initial reattachment rate and is associated with better postoperative visual
      acuity at 12 months. Therefore, ICG staining should be used during vitrectomy for
      MHRD because the complete removal of the ILM with ICG ensures the removal of the
      tangential traction by an epiretinal membrane and the inverse traction by the
      retina that cannot follow the posterior enlargement of a staphyloma.

PMID- 17194479
TI  - Scleral buckling surgery after macula-off retinal detachment: worse visual
      outcome after more than 6 days.
AB  - PURPOSE: To determine the effect of duration of macular detachment (DMD) on
      visual acuity (VA) in patients with macula-off rhegmatogenous retinal detachment
      (RD). DESIGN: Retrospective observational case series. PARTICIPANTS: Two hundred
      two consecutive patients (202 eyes) with primary uncomplicated macula-off RD,
      preoperative VA of 10/100 or worse, a precise history of when macular function
      was lost, successful reattachment surgery, and a minimal follow-up of 3 months.
      INTERVENTION: All RDs were repaired with a primary scleral buckling procedure
      performed by 3 vitreoretinal surgeons. MAIN OUTCOME MEASURE: Visual acuity (best
      corrected and 3, 6, and 12 months postoperatively). RESULTS: Considering all
      eyes, the cumulative mean of the best-corrected postoperative VA (logarithm of
      the minimum angle of resolution [logMAR]) as a function of DMD shows a rapid
      worsening when DMD exceeds 6 days. Eyes were divided into 3 groups, corresponding
      to the DMD intervals immediate (within 10 days), delayed (11 days-6 weeks), and
      late (>6 weeks). Mean postoperative VAs (in logMAR) were 0.35+/-0.31 (between
      20/40 and 20/50 Snellen equivalent) in eyes with DMD up to 10 days, 0.48+/-0.26
      (20/60 Snellen equivalent) in the delayed group, and 0.86+/-0.30 (8/60 Snellen
      equivalent) in eyes with DMD longer than 6 weeks. CONCLUSIONS: The cumulative
      mean of the best-corrected postoperative VA (logMAR) as a function of DMD shows a
      rapid worsening when DMD exceeds 6 days. Our results indicate that the scleral
      buckling procedure should be done preferably within a 7-day DMD.

PMID- 17194480
TI  - Impact of peginterferon alpha-2b and ribavirin treatment on liver tissue in
      patients with HCV or HCV-HIV co-infection.
AB  - OBJECTIVE: To evaluate the effect of treatment with peginterferon alpha-2b and
      ribavirin on liver histology in patients with chronic hepatitis C (CHC) with or
      without HIV infection. METHODS: Patients received peginterferon alpha-2b (1.5
      micro/kg/week during the first 4 weeks; 1.0 micro/kg/week thereafter) plus
      ribavirin (800-1200 mg/day, adjusted for weight) for 24 (genotypes 2/3) or 48
      weeks (genotypes 1/4). Paired liver biopsy specimens were obtained at baseline
      and at the end of follow-up. RESULTS: 108 paired biopsy specimens were available:
      67 from HCV-monoinfected and 41 from co-infected patients. At the end of follow
      up, necroinflammatory activity (NIA) was significantly reduced (P<0.001), and
      fibrosis scores improved by > or = 1 point (Ishak et al criteria) in 65.7% of HCV
      monoinfected patients. In co-infected patients, NIA was significantly reduced
      (P<0.001), and fibrosis scores improved by > or = 1 point in 42.5% of cases. In
      both groups, results were better for patients who attained sustained virological
      response (SVR). HCV RNA was undetectable in the second biopsy specimens of all
      patients who attained SVR. CONCLUSION: Liver fibrosis is reduced significantly
      after a course of therapy in patients with chronic hepatitis C. Reduction of
      fibrosis is more significant in patients who are monoinfected with HCV and in
      those who attained SVR.

PMID- 17194481
TI  - IL-12 producing monocytes and IFN-gamma and TNF-alpha producing T-lymphocytes are
      increased in placentas infected by Plasmodium falciparum.
AB  - Placental Plasmodium falciparum sequestration is associated with dysregulated
      immune function. Placental inflammatory responses via IFN-gamma and TNF-alpha are
      implicated in functional damage. However, they are needed during placental
      infection to control asexual stage parasites. To test the hypothesis that
      placental immunomodulation associated with malaria disturbs cytokine secretion
      differently in monocytes and lymphocytes, we have determined the proportion of
      monocytes and/or lymphocytes secreting IFN-gamma, TNF-alpha, IL-10 and IL-12.
      Intervillous and peripheral blood monocyte (CD14+) and lymphocyte (CD3/CD4+;
      CD3/CD8+) cytokine production was compared between 17 P. falciparum-infected and
      12 non-infected Senegalese women. After culture with phorbolmyristate
      acetate/ionomycin (PMA/iono), lipopolysaccharide (LPS) or P. falciparum-infected
      erythrocytes (IE), the intracellular expression of cytokines in lymphocytes (IFN
      gamma, TNF-alpha) and monocytes (IL-10, IL-12, TNF-alpha), was detected. In
      response to IE, CD4+ and CD8+ T-cells produced IFN-gamma and TNF-alpha at similar
      rates in both compartments. In response to PMA/iono, the frequencies of CD4+ and
      CD8+ T-cells producing IFN-gamma and TNF-alpha were similar in both compartments,
      but increased in P. falciparum-infected placentas. In response to LPS or IE, IL
      12 secreting monocytes were increased in infected women, while the frequency of
      TNF-alpha secreting monocytes was decreased compared to that in non-infected
      placenta. The monocyte IL-12 response is not impaired in infected women. IL-12 is
      an important factor for inducing IFN-gamma in T-cells. Thus, IL-12 and IFN-alpha
      responses may synergistically allow a protective immune response in placental
      malaria. TNF-alpha production by CD4+ and CD8+ T-cells is up-regulated in P.
      falciparum-infected placentas, suggesting that T-cells actively participate to
      inflammatory responses.

PMID- 17194482
TI  - Perfusion with lipopolysaccharide differently affects the secretion of tumor
      necrosis factor-alpha and interleukin-6 by term and preterm human placenta.
AB  - This study has compared the functional capacity of term and preterm placentas in
      terms of production of pro-inflammatory cytokines in a perfusion system
      reflecting their ability to react to inflammatory agents, such as
      lipopolysaccharide (LPS), mimicking the situation of chorioamnionitis. We have
      demonstrated that term placentas secrete higher levels of tumor necrosis factor
      (TNF)-alpha compared with preterm placentas. Moreover, TNF-alpha secretion was
      significantly higher after exposure to LPS in the maternal and fetal sides of
      term placentas. In contrast, in preterm placentas, only the fetal side responded
      with a significant increase in secretion of TNF-alpha after exposure to LPS. The
      maternal side of term placentas secreted significantly higher amounts of
      interleukin (IL)-6 compared with preterm placentas. Exposure to LPS significantly
      decreased IL-6 secretion from the maternal side in both term and preterm
      placentas. Moreover, the fetal side of term placentas secreted significantly
      lower amounts of IL-6 compared with preterm placentas. In summary, this study has
      indicated that term and preterm placental tissues have a differing responsiveness
      to LPS stimulation, with term placentas disposed to a higher TNF-alpha:IL-6
      ratio. Release of cytokines into fetal circulation is less than into the maternal
      side. However, TNF-alpha is released into fetal circulation after LPS stimulation
      and this may be relevant to the etiology of chorioamnionitis.

PMID- 17194483
TI  - Systemic innate immune responses following intrapulmonary delivery of CpG
      oligodeoxynucleotides in sheep.
AB  - Mucosal delivery of CpG oligodeoxynucleotide (ODN) in mice has been shown to
      induce potent innate immunostimulatory responses and protection against
      infection. We evaluated the efficacy of CpG ODN in stimulating systemic innate
      immune responses in sheep following delivery to the pulmonary mucosa.
      Intrapulmonary (IPM) administration of B-Class CpG ODN in saline induced
      transient systemic responses which included increased rectal temperatures,
      elevated serum 2'5'-A synthetase and haptoglobin concentrations. The ODN dose
      required to induce detectable systemic responses following IPM delivery could be
      reduced by approximately 80% if the CpG ODN was administered in 30% emulsigen
      instead of saline. Intrapulmonary B-Class CpG ODN formulated in 30% emulsigen
      produced similar effects when compared to those seen following SC injection.
      These responses were CpG ODN-specific since control GpC ODN did not induce any
      detectable response. Intrapulmonary administration of both B-Class and the newly
      described C-Class CpG ODN produced similar effects indicating that both classes
      of CpG ODN were comparably effective in stimulating innate immune system
      following mucosal delivery. Administration of CpG ODN directly into the lungs or
      delivery of CpG ODN via an intratracheal (IT) infusion also produced similar
      systemic responses. These observations support the conclusion that mucosal
      delivery of CpG ODN is an effective route for induction of systemic acute phase
      responses and antiviral effector molecules in large animals, and may be helpful
      in controlling systemic infections.

PMID- 17194484
TI  - Common gamma chain cytokines: dissidence in the details.
AB  - Cytokines of the common cytokine-receptor gamma-chain (gamma(c)) family are
      essential for the development and maintenance of lymphocytes. Herein, we will
      focus on the roles of interleukin-2 (IL-2), IL-7, IL-15 and IL-21, in the
      orchestration of CD8 T cell responses. Among these cytokines, IL-7 has emerged as
      a master regulator of survival of immature and mature T lymphocytes, while IL-2,
      IL-15 and IL-21 appear to have specific functions in T cell homeostasis and
      differentiation. Hence, the gamma(c) has evolved as an elegant anchor through
      which related cytokines regulate distinct biological responses in T cells.

PMID- 17194485
TI  - Rapid and simple detection of Ebola virus by reverse transcription-loop-mediated
      isothermal amplification.
AB  - Ebola virus (EBOV) causes severe hemorrhagic fever in humans and nonhuman
      primates with high mortality rates. Rapid identification of the virus is required
      to prevent spread of the infection. In this study, we developed and evaluated a
      one-step simple reverse transcription-loop mediated isothermal amplification (RT
      LAMP) assay for the rapid detection of Zaire ebolavirus (ZEBOV), the most
      virulent species of EBOV, targeting the trailer region of the viral genome. The
      assay could detect 20 copies of the artificial ZEBOV RNA in 26 min with a real
      time-monitoring detection, and also detect 10(-3) FFU of the cell-culture
      propagated viruses. The reaction time needed to detect 10(4) FFU of ZEBOV was
      only 20 min. In addition, the assay was highly specific for ZEBOV. The RT-LAMP
      assay developed in this study is rapid, simple, highly specific, and sensitive
      for the detection of ZEBOV, and so may be an effective diagnostic tool.
      Furthermore, as this technique does not require sophisticated instrumentation, it
      seems very suitable for diagnosis in the field or laboratories in Ebola outbreak
      areas such as Central Africa.

PMID- 17194486
TI  - Drug-resistant HIV-1 prevalence in patients newly diagnosed with HIV/AIDS in
      Japan.
AB  - The increasing prevalence of drug-resistant HIV transmission has become a
      critical epidemic in the world today. Studies in developed countries reported 8
      27% of newly diagnosed HIV/AIDS patients are infected by drug-resistant strains.
      To determine the prevalence of drug-resistant HIV-1 among newly diagnosed cases
      in Japan, eight HIV/AIDS clinical centers, three public health laboratories and
      the National Institute of Infectious Diseases conducted a nationwide survey.
      Between January 2003 and December 2004, 575 newly diagnosed HIV/AIDS patients
      with both acute and chronic infections were enrolled in the study. Twenty-three
      cases, including three recently infected patients, were infected with HIV-1
      having major drug-resistance mutations, including M41L, D67N, L100I, K103N,
      V106A, M184I, M184V, L210W, and revertant mutations at the 215 codon in reverse
      transcriptase and M46I in protease encoding regions. In this newly diagnosed
      population, we also clarified the prevalence of hepatitis virus coinfection,
      which was 8.8% for HBV and 4.3% for HCV. In conclusion, the drug-resistant
      transmission rate was 4.0% in Japan. Although this rate is significantly lower
      than that of other developed countries, this rate almost reaches the threshold at
      which baseline genotypic resistance testing would be cost-effective for all
      infected persons before initiating therapy.

PMID- 17194487
TI  - CD81 down-regulation on B cells is associated with the response to interferon
      alpha-based treatment for chronic hepatitis C virus infection.
AB  - The lymphocytic CD81 molecule, capable of modulating type-1/-2 T-helper responses
      and serving as a putative receptor for hepatitis C virus (HCV), might influence
      the outcome of anti-HCV treatment. This study characterized the interferon-alpha
      induced alteration of lymphocytic CD81. The CD81 levels in healthy subjects and
      naive chronic HCV patients were compared, with the results showing that the two
      groups had comparable surface CD81 levels for total peripheral blood lymphocytes,
      subpopulation-B, -T, and -NK cells. In vitro interferon-alpha treatment could
      suppress the CD81 expression from both groups. Subsequently, we compared the in
      vitro interferon-alpha modulatory effects on lymphocytic CD81 from patients
      having received anti-HCV therapy with either sustained virological response (SVR)
      or without SVR. There was a significant down-regulation of the B-cell's CD81 only
      in the SVR group. The CD81 modulation was further investigated using Daudi
      lymphoid cell line, showing declined surface CD81 levels following treatment with
      interferon-alpha, interferon-beta or polyI:C. Thus, interferons could directly
      decrease CD81 expression. The interferon-alpha effect could be restored by 2
      aminopurine, suggesting that double-stranded RNA activated kinase might be
      involved in the suppression of CD81. In conclusion, CD81 down-regulation is a
      primary host response to interferon-alpha-based therapy and an immunophenotype
      associated with anti-HCV SVR.

PMID- 17194488
TI  - Inhibition of lesion-induced neurogenesis impaired behavioral recovery in adult
      ring doves.
AB  - We have previously shown that electrolytic lesion-induced neurogenesis in the
      ventromedial nucleus of the hypothalamus (VMN) is significantly correlated with
      the recovery of courtship behavior in adult male ring doves. Here we revealed
      that reduction of lesion-induced neurogenesis in VMN impaired the behavioral
      recovery suggesting therefore a causal link between neurogenesis and behavioral
      recovery. Our results lend support that adult neurogenesis is latent in repair of
      injured brain.

PMID- 17194489
TI  - Differential susceptibility following beta-amyloid peptide-(1-40) administration
      in C57BL/6 and Swiss albino mice: Evidence for a dissociation between cognitive
      deficits and the glutathione system response.
AB  - Considerable evidence supports the role of oxidative stress in the pathogenesis
      of Alzheimer's disease (AD). Previous studies suggest that the central nervous
      system (CNS) administration of beta-amyloid peptide, the major constituent of
      senile plaque in AD, induces oxidative stress in rodents which may contribute to
      the learning and memory deficits verified in the beta-amyloid model of AD. In the
      present study, we compared the effects of a single intracerebroventricular
      (i.c.v.) injection of aggregated beta-amyloid peptide-(1-40) (Abeta(1-40))
      (400pmol/mouse) on spatial learning and memory performance, synaptic density and
      the glutathione (GSH)-dependent antioxidant status in adult male C57BL/6 and
      Swiss albino mice. Seven days after Abeta(1-40) administration, C57BL/6 and Swiss
      mice presented similar spatial learning and memory impairments, as evaluated in
      the water maze task, although these impairments were not found in Abeta(40-1)
      treated mice. Moreover, a similar decline of synaptophysin levels was observed in
      the hippocampus (HC) and prefrontal cortex (PFC) of both Swiss and C57BL/6 mice
      treated with Abeta(1-40), which suggests synaptic loss. C57BL/6 mice presented
      lower levels of glutathione-related antioxidant defences (total glutathione (GSH
      t) levels, glutathione peroxidase (GPx) and glutathione reductase (GR) activity)
      in the HC and PFC in comparison to Swiss mice. Despite the reduced basal GSH
      dependent antioxidant defences observed in C57BL/6 mice, Abeta(1-40)
      administration induced significant alterations in the brain antioxidant
      parameters only in Swiss mice, decreasing GSH-t levels and increasing GPx and GR
      activity in the HC and PFC 24h after treatment. These results indicate strain
      differences in the susceptibility to Abeta(1-40)-induced changes in the GSH
      dependent antioxidant defences in mice, which should be taken into account in
      further studies using the Abeta model of AD in mice. In addition, the present
      findings suggest that the spatial learning and memory deficits induced by beta
      amyloid peptides in rodents may not be entirely related to glutathione-dependent
      antioxidant response.

PMID- 17194490
TI  - Influence of food quality and salinity on dietary cadmium availability in Mytilus
      trossulus.
AB  - Surficial sediments (a combination of re-suspended and suspended sediments
      denoted as RSS) were collected from two distinct marine intertidal habitats. The
      two habitats differed with respect to salinity (25ppt versus 15ppt) and RSS %
      organic carbon content (24% versus 15%). Feeding experiments were conducted
      simulating the conditions in the two habitats to determine if salinity and RSS %
      organic carbon content affected cadmium accumulation in the pacific blue mussel
      Mytilus trossulus. Eleven different treatments including pure phytoplankton,
      collected RSS and control clay were radiolabeled with (109)Cd and pulse-fed to M.
      trossulus under both high (25ppt) and low salinities (15ppt). Metal uptake and
      accumulation was determined using the DYMBAM biodynamic metal bioaccumulation
      model. Although M. trossulus ingestion rates (IR) were significantly higher at
      25ppt as compared to 15ppt, assimilation efficiencies (AEs) and [(109)Cd] tissue
      levels were significantly lower at high as compared to low salinity exposures. Of
      the abiotic and biotic parameters examined and in contrast to other studies,
      differences in salinity rather than ingestion rate or food quality (as defined by
      % organic carbon content) seemed to best define the observed differences in
      (109)Cd AE by M. trossulus.

PMID- 17194491
TI  - Combined effects of herbicides on biomarkers reflecting immune-endocrine
      interactions in goldfish. Immune and antioxidant effects.
AB  - Goldfish (Carassius auratus) were exposed to a mixture of herbicides, namely
      atrazine, simazine, diuron, and isoproturon (ASDI) at a cumulative concentration
      of 50microg/l for 12 weeks. Control fish and exposed fish were sampled at 4, 8
      and 12 weeks of exposure to observe the combined impact of herbicides on non
      specific and specific mechanisms of immunity and antioxidant defenses. The
      antioxidant defenses were evaluated in haemopoietic organs and liver. ASDI
      induced stress was reflected as a significant induction of superoxide (O(2)(-))
      production in phagocytic cells of head kidney and spleen. In addition, plasma
      lysozyme activity was consistently high in the treatment group. Specific immunity
      was assessed by antibody titre responses following immunization of the fish with
      sheep red blood cells (SRBCs). Antibody titre was reduced throughout the period
      of observation in ASDI-treated fish. This reduction was found to be significant
      at week 4 (p<0.05). Herbicide-exposed fish showed reduced resistance against
      pathogen invasion but remarkable enhancement in lysozyme activity. The ASDI
      induced oxidative stress in spleen, kidney and liver was reflected as a change in
      the antioxidant enzyme activities in these vital organs of fish. Our data
      indicate that herbicides at concentrations present in water bodies in Europe
      cause immune suppression in goldfish.

PMID- 17194492
TI  - Characterisation of macrophage migration inhibitory factor from Eimeria species
      infectious to chickens.
AB  - Macrophage migration inhibitory factor (MIF) was the first cytokine to be
      identified almost 40 years ago. Homologues of MIF have been isolated recently
      from invertebrates, making it an interesting molecule from an evolutionary as
      well as functional perspective. The present study represents the first report of
      MIF homologues in apicomplexan parasites, belonging to the genus Eimeria. A
      single full-length clone was isolated from Eimeria acervulina that shared between
      35 and 38% amino acid identity with MIFs of vertebrates. A MIF cDNA from Eimeria
      tenella shared 64% amino acid identity with E. acervulina MIF. The mRNA
      expression was highest in merozoites, whereas developing oocysts and sporozoites
      expressed low to undetectable levels. Protein expression patterns were nearly
      identical to that observed by reverse transcriptase polymerase chain reaction (RT
      PCR), suggesting strong developmental regulation. Immunofluorescence staining and
      co-localisation studies of E. acervulina merozoites indicated that MIF is
      distributed throughout the cytosol, and appears to be concentrated in the apical
      end of the parasite. The presence of MIF was detected in excretory/secretory (ES)
      products collected from E. acervulina merozoites, and isoelectric focusing
      indicated that three MIF isoforms are present in this stage. Phylogenetic
      analysis revealed that apicomplexan MIF sequences form a sister relationship to
      MIF-like molecules from Arabidopsis thaliana.

PMID- 17194494
TI  - A treatment planning study comparing whole breast radiation therapy against
      conformal, IMRT and tomotherapy for accelerated partial breast irradiation.
AB  - PURPOSE AND BACKGROUND: Conventional early breast cancer treatment consists of a
      lumpectomy followed by whole breast radiation therapy. Accelerated partial breast
      irradiation (APBI) is an investigational approach to post-lumpectomy radiation
      for early breast cancer. The purpose of this study is to compare four external
      beam APBI techniques, including tomotherapy, with conventional whole breast
      irradiation for their radiation conformity index, dose homogeneity index, and
      dose to organs at risk. METHODS AND MATERIALS: Small-field tangents, three
      dimensional conformal radiation therapy, intensity-modulated radiation therapy
      and helical tomotherapy were compared for each of 15 patients (7 right, 8 left).
      One radiation conformity and two dose homogeneity indices were used to evaluate
      the dose to the target. The mean dose to organs at risk was also evaluated.
      RESULTS: All proposed APBI techniques improved the conformity index significantly
      over whole breast tangents while maintaining dose homogeneity and without a
      significant increase in dose to organs at risk. CONCLUSION: The four-field IMRT
      plan produced the best dosimetric results; however this technique would require
      appropriate respiratory motion management. An alternative would be to use a four
      field conformal technique that is less sensitive to the effects of respiratory
      motion.

PMID- 17194493
TI  - Clinical experience of MEK inhibitors in cancer therapy.
AB  - Finding new therapies to assist in the treatment of cancer is a major challenge
      of clinical research. Small molecules that inhibit different molecular targets at
      the different levels of the MAPK pathway have been developed. Several MEK
      inhibitors have been examined in early-phase clinical trials and the current
      state of clinical results using these therapies is presented here.

PMID- 17194496
TI  - PCR-suppression effect: kinetic analysis and application to representative or
      long-molecule biased PCR-based amplification of complex samples.
AB  - In the present study, we analyzed the kinetics of the PCR-suppression effect (PS
      effect) and firstly demonstrate that lower annealing temperature enhances PS
      effect. Furthermore, we controlled the average size of complex PCR products over
      a wide range, and simultaneously amplified targets from 0.25 to 10kb by
      regulating the degree of suppression in a single-primer PCR. In addition, we
      describe an improved template-switching full-length cDNA synthesis method that
      greatly reduces truncated cDNA. This study provides a general guide for the
      design of PS-effect related PCR and is useful for representative or long
      transcript enriched cDNA library construction, especially when only a small
      amount of total RNA is available.

PMID- 17194495
TI  - Cloning, functional expression and characterization of Aspergillus sulphureus
      beta-mannanase in Pichia pastoris.
AB  - Using RT-PCR and rapid amplication of cDNA ends (RACE) techniques, a 1345bp full
      length cDNA fragment was obtained from Aspergillus sulphureus. The gene,
      designated MANN, codes for a 383-residue with a calculated mass of 41,389Da. MANN
      displayed amino acid sequence similarity to the beta-mannanase of Aspergillus
      aculeatus and Trichoderma reesei, members of the glycoside hydrolase family 5.
      The recombinant beta-mannanase gene was successfully expressed in a fully active
      form in Pichia pastoris. Southern blot analysis showed that the recombinant beta
      mannanase gene had successfully integrated into the P. pastoris X-33 genome. SDS
      PAGE and Western blot assays demonstrated that the recombinant beta-mannanase, a
      48kDa glycosylated protein, was secreted into the culture medium. The enzyme had
      high specific activity toward locust bean gum and an extremely broad pH range of
      2.2-8.0. It showed highest activity at pH 2.4 and 50 degrees C and was stable at
      temperature below 40 degrees C. The K(m) and V(max) values for locust bean gum at
      50 degrees C and pH 2.4 are 0.93mgmL(-1) and 344.83Umg(-1), respectively. The
      isoelectric point of the recombinant protein is 4.89. The enzymatic activity of
      recombinant A. sulphureus beta-mannanase was not significantly affected by a
      range of ions or EDTA.

PMID- 17194497
TI  - Acidification improves cryotolerance of Lactobacillus delbrueckii subsp.
      bulgaricus CFL1.
AB  - The effect of acidification of the fermented broth at the end of the culture was
      examined on the growth and the cryotolerance of Lactobacillus bulgaricus CFL1, as
      a new means to better preserve lactic acid bacteria. Cryotolerance was
      investigated by evaluating the loss of specific acidification activity during
      freezing and frozen storage. An experimental design made it possible to determine
      optimal acidification conditions that improved cryotolerance, such as pH 5.15 for
      30min. These conditions were also conducive to high biomass productivity. By
      considering the type of acid used, H(2)SO(4) enabled us to obtain cells with
      better cryotolerance, as compared to HCl. It was also observed that increasing
      the pH after acidification slightly minimised the acid shock, thus improving
      cryotolerance. Moreover, it was concluded that this improvement was related to a
      physiological adaptation of L. bulgaricus CFL1 during the 30-min acidification at
      pH 5.15.

PMID- 17194499
TI  - NPY/AgRP neurons are not essential for feeding responses to glucoprivation.
AB  - Animals respond to hypoglycemia by eating and by stimulating gluconeogenesis.
      These responses to glucose deprivation are initiated by glucose-sensing neurons
      in the brain, but the neural circuits that control feeding behavior are not well
      established. Neurons in the arcuate region of the hypothalamus that express
      neuropeptide Y (NPY) and agouti-related protein (AgRP) have been implicated in
      mediating the feeding response to glucoprivation. We devised a method to
      selectively ablate these neurons in neonatal mice and then tested adult mice for
      their feeding responses to fasting, mild hypoglycemia, 2-deoxy-d-glucose and a
      ghrelin receptor agonist. Whereas the feeding response to the ghrelin receptor
      agonist was completely abrogated, the feeding response to glucoprivation was
      normal. The feeding response after a fast was attenuated when standard chow was
      available but normal with more palatable solid or liquid diet. We conclude that
      NPY/AgRP neurons are not necessary for generating or mediating the orexigenic
      response to glucose deficiency, but they are essential for the feeding response
      to ghrelin and refeeding on standard chow after a fast.

PMID- 17194498
TI  - Common polymorphisms in D12S1034 flanking genes RASSF8 and BHLHB3 are not
      associated with lung adenocarcinoma risk.
AB  - The reported association between D12S1034 and lung adenocarcinoma (ADCA) risk
      [Yanagitani N, Kohno T, Sunaga N, et al. Localization of a human lung
      adenocarcinoma susceptibility locus, possibly syntenic to the mouse Pas1 locus,
      in the vicinity of the D12S1034 locus on chromosome 12p11.2-p12.1.
      Carcinogenesis. 2002;23:1177-83] prompted us to carry out a case-control study in
      lung ADCA and healthy control subjects to test possible involvement of single
      nucleotide polymorphisms (SNPs) in D12S1034 flanking genes RASSF8 and BHLHB3,
      whose minimal distances from D12S1034 are approximately 16-24 kb. RASSF8 contains
      a RAS-associated domain and is a candidate tumor suppressor, whereas BHLHB3 is a
      basic helix-loop-helix domain-containing protein that functions as a
      transcriptional repressor. We observed no significant association between common
      SNPs in RASSF8 (rs1546550 in the 3'-UTR and 3 intronic SNPs) and BHLHB3
      (Ala298Val and rs1048155 in the 3'-UTR) with lung ADCA risk. However, patient
      groups carrying one or two copies of the BHLHB3 Val298 variation (i.e., Ala/Val
      or Val/Val genotypes) had a higher proportion of short-term survivors (hazard
      ratio, 1.8; 95% confidence interval, 1.2-2.7) compared with those carrying the
      Ala/Ala genotype. A replication study in an independent Norwegian lung cancer
      population of multiple cancer histotypes failed to replicate the significant
      association of BHLHB3 Ala298Val with survival; such association, however, was
      confirmed by analysis of ADCA only from both populations. Our results suggest
      that BHLHB3 variants may affect lung ADCA prognosis.

PMID- 17194500
TI  - Purification and characterization of eight peptides from Galleria mellonella
      immune hemolymph.
AB  - Defense peptides play a crucial role in insect innate immunity against invading
      pathogens. From the hemolymph of immune-challenged greater wax moth, Galleria
      mellonella (Gm) larvae, eight peptides were isolated and characterized. Purified
      Gm peptides differ considerably in amino acid sequences, isoelectric point values
      and antimicrobial activity spectrum. Five of them, Gm proline-rich peptide 2, Gm
      defensin-like peptide, Gm anionic peptides 1 and 2 and Gm apolipophoricin, were
      not described earlier in G. mellonella. Three others, Gm proline-rich peptide 1,
      Gm cecropin D-like peptide and Galleria defensin, were identical with known G.
      mellonella peptides. Gm proline-rich peptides 1 and 2 and Gm anionic peptide 2,
      had unique amino acid sequences and no homologs have been found for these
      peptides. Antimicrobial activity of purified peptides was tested against gram
      negative and gram-positive bacteria, yeast and filamentous fungi. The most
      effective was Gm defensin-like peptide which inhibited fungal and sensitive
      bacteria growth in a concentration of 2.9 and 1.9 microM, respectively. This is
      the first report describing at least a part of defense peptide repertoire of G.
      mellonella immune hemolymph.

PMID- 17194501
TI  - PYY and the pancreas: inhibition of tumor growth and inflammation.
AB  - Peptide YY (PYY) orchestrates function of the gut and pancreas by regulating
      growth, digestion and absorption. In addition to its physiological role, PYY
      exhibits immune and antitrophic properties in the pancreas by decreasing cytokine
      and amylase release. Although the exact mechanism(s) of action are still not
      fully understood, PYY interacts at the acinar level with numerous intracellular
      transcription factors. In addition to ameliorating pancreatic inflammation, novel
      synthetic analogs of PYY have been developed that are potent inhibitors in the
      proliferation of pancreatic cancer. The present paper reviews our current
      findings with PYY and examines the therapeutic implications of its utility in
      treating inflammation and cancer.

PMID- 17194502
TI  - Periaqueductal gray cholecystokinin infusions block morphine-induced disruption
      of maternal behavior.
AB  - Cholecystokinin (CCK) and opiates interaction is critical for maintaining
      maternal behavior during lactation. Morphine inhibits while CCK restores maternal
      behavior. Recently we have shown that periaqueductal gray (PAG) is a region
      critically involved in the opioidergic blockade of maternal behavior. A critical
      level of morphine-induced activation of the rostral lateral PAG is required to
      inhibit maternal behavior in lactating rats. Since central CCK injections
      reverted morphine-induced inhibition of maternal behavior, we tested whether this
      peptide would act similarly in the PAG. This hypothesis was confirmed in
      experiments showing that morphine's inhibitory effect on maternal responsiveness
      was blocked by 1.0 and 0.2 nmol CCK injections into the rostral PAG, but not in
      nearby regions of the mesencephalic reticular nucleus. To test for possible
      compensatory changes the CCK2 receptor due to morphine treatments the expression
      of CCK2 receptor mRNA was evaluated in the PAG. PAG CCK2 receptor cDNA
      amplification revealed no difference in morphine treated animals. These results
      broaden understanding of the role played by CCK in the PAG. This CCK action might
      not depend on changes in its receptor.

PMID- 17194503
TI  - Peptide YY: a neuroendocrine neighbor of note.
AB  - Endocrine cells, enteric neurons and enterocytes provide an integrated functional
      defense against luminal factors, including nutrients, microbes and toxins.
      Prominent among intrinsic mediators is peptide YY (PYY) which is present in
      approximately 50% of colorectal endocrine cells and neuropeptide Y (NPY), a
      neurotransmitter expressed in submucous and myenteric nerves. Both peptides and
      their long fragments (PYY(3-36) and NPY(3-36)) are potent, long-lasting anti
      secretory agents in vitro and in vivo and, they provide significant Y receptor
      mediated absorptive tone in human and mouse colon mucosa. The main function of
      the colon is to absorb 90% of approximately 2l of daily ileal effluent (in adult
      humans) and Y-absorptive tone can contribute significantly to this electrolyte
      absorption. Blockade or loss of this mucosal Y-absorptive tone (i.e. with Y(1) or
      Y(2) antagonists) leads to hypersecretion and potentially to diarrhea, so Y
      agonists are predicted to rescue absorption by mimicking endogenous
      neuroendocrine PYY or neuronal NPY.

PMID- 17194504
TI  - Role of NPY for vasoregulation in the splanchnic circulation during portal
      hypertension.
AB  - Vascular dysfunction in the splanchnic circulation during portal hypertension is
      characterized by enhanced NO-mediated vasorelaxation and vascular hyporeactivity
      to norepinephrine that lead to arterial vasodilation. NPY most likely counteracts
      both of these key features. Firstly, NPY appears to inhibit Ach- and PNS-induced
      vasorelaxation in mesenteric arteries. This effect is more pronounced in portal
      hypertensive rats as compared to control, and most likely reflects the inhibition
      of increased e- and nNOS-derived NO-synthesis during portal hypertensive
      conditions. Secondly, NPY sensitizes the mesenteric vasculature to alpha(1)
      adrenergic vasoconstriction. Most importantly, in portal hypertensive rats but
      not in sham rats NPY markedly augments vascular contractility and thereby
      corrects vascular hyporeactivity. Both actions of NPY increase vascular tone and
      may well act synergistically in the splanchnic circulation during portal
      hypertension. Moreover, the vasoconstrictive effects of NPY are most pronounced
      at particularly high levels of alpha(1)-adrenergic activity. Therefore, it
      appears that NPY becomes increasingly important for optimizing adrenergic
      vasoconstriction at particularly high adrenergic drive and also for playing a
      predominant role for vascular homeostasis. Cirrhotic patients present with
      elevated circulating plasma levels of NPY, which appears to be independent from
      the severity of liver dysfunction and to correlate with portal pressure. This
      finding indicates enhanced NPY release during portal hypertension that may
      represent a compensatory mechanism aimed at counterbalancing arterial
      vasodilation by restoring the efficacy of endogenous catecholamines and
      inhibiting vasodilative drive in the splanchnic circulation.

PMID- 17194505
TI  - The Y2 receptor mediates increases in collateral-dependent blood flow in a model
      of peripheral arterial insufficiency.
AB  - We have utilized a rat model of peripheral artery disease (PAD) to examine
      whether the known angiogenic activity of the Y(2) receptor would translate into a
      meaningful increase in collateral blood flow. The maximal increase in collateral
      blood flow capacity of approximately 60% (p<0.001) was obtained with a
      10microg/kgday (IA infusion, 14 days) of either PYY or PYY(3-36) and did not
      differ from that obtained with a maximally angiogenic dose of VEGF(165).
      Pharmacodynamic modeling based upon single dose pharmacokinetic plasma profiles
      of both agonists suggests that E(max) is reached when the Y(2) receptor is
      occupied by >or=50%. Furthermore, for PYY(3-36), occupancy of the Y(2) receptor
      is sufficient to promote a significant benefit in collateral blood flow.

PMID- 17194506
TI  - Spinal mechanisms of NPY analgesia.
AB  - We review previously published data, and present some new data, indicating that
      spinal application of neuropeptide Y (NPY) reduces behavioral and
      neurophysiological signs of acute and chronic pain. In models of acute pain,
      early behavioral studies showed that spinal (intrathecal) administration of NPY
      and Y2 receptor agonists decrease thermal nociception. Subsequent
      neurophysiological studies indicated that Y2-mediated inhibition of excitatory
      neurotransmitter release from primary afferent terminals in the substantia
      gelatinosa may contribute to the antinociceptive actions of NPY. As with acute
      pain, NPY reduced behavioral signs of inflammatory pain such as mechanical
      allodynia and thermal hyperalgesia; however, receptor antagonist studies indicate
      an important contribution of spinal Y1 rather than Y2 receptors. Interestingly,
      Y1 agonists suppress inhibitory synaptic events in dorsal horn neurons (indeed,
      well known mu-opioid analgesic drugs produce similar cellular actions). To
      resolve the behavioral and neurophysiological data, we propose that NPY/Y1
      inhibits the spinal release of inhibitory neurotransmitters (GABA and glycine)
      onto inhibitory neurons, e.g. disinhibition of pain inhibition, resulting in
      hyporeflexia. The above mechanisms of Y1- and Y2-mediated analgesia may also
      operate in the setting of peripheral nerve injury, and new data indicate that NPY
      dose-dependently inhibits behavioral signs of neuropathic pain. Indeed,
      neurophysiological studies indicate that Y2-mediated inhibition of Ca(2+) channel
      currents in dorsal root ganglion neurons is actually increased after axotomy. We
      conclude that spinal delivery of Y1 agonists may be of use in the treatment of
      chronic inflammatory pain, and that the use of Y1 and Y2 agonists in neuropathic
      pain warrants further consideration.

PMID- 17194507
TI  - Self-regulation of agonist activity at the Y receptors.
AB  - Neuropeptide Y (NPY) is one of the most abundant neuropeptides, and is likely to
      be present at nanomolar levels over extended periods in the synaptic space of
      many forebrain areas. This might be linked to an evolved generalized toning
      activity through a number of other peptide receptors that use C-terminally
      amidated agonists (with LHRH and orexin receptors and GIR as examples). However,
      the Y1 and Y2 receptors (which constitute the bulk of Y receptors active in the
      neural matrix) possess subnanomolar affinities that, at saturating NPY levels,
      could produce excessive signaling, as well as receptor losses via repeated
      endocytosis. The related Y4 receptor shows an even higher agonist affinity, and
      faces the same problem in visceral and neural locations accessible to pancreatic
      polypeptide (PP). An examination of agonist peptide interaction with Y receptors
      shows that Y1 and Y4 receptors in particular (as located on either the intact
      cells, or on particulates derived from various cell types) develop a blockade
      dependent on ligand concentration, with the blocking ranks of [NPY]>>[peptide YY]
      (PYY) for the Y1, and [human PP]>>>[PYY-related Y4 agonist] for the Y4 receptor.
      This blockade is also echoed in a concentration-related reduction in biological
      activity of primary agonists (NPY and PP), resembling a partial agonism, and is
      influenced especially by the allosteric interactivity of agonists. With the Y2
      receptor, the blocking by agonists is less pronounced, but the signaling by NPY
      related peptides is apparently less than with PYY-related agonists. The extended
      occupancy and self-attenuation of primary agonist activity at Y receptors could
      represent an evolutionary solution contributing to a balancing of metabolic
      signaling, agonist clearance and receptor conservation.

PMID- 17194508
TI  - Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro
      salicylaldehyde.
AB  - A series of Schiff bases (compounds 1-26) were synthesized by reacting 5-chloro
      salicylaldehyde and primary amines, 15 (compounds 2-4, 6, 7, 10, 12-17, 23, 25
      and 26) of which were first reported. The chemical structures of these compounds
      were confirmed by means of (1)H NMR, (13)C NMR, ESI-MS and elemental analyses.
      The compounds were assayed for antibacterial (Bacillus subtilis, Escherichia
      coli, Pseudomonas fluorescence and Staphylococcus aureus) and antifungal
      (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT
      (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trtrazolium bromide) method. Among the
      compounds tested, (E)-4-chloro-2-((4-fluorobenzylimino)methyl)phenol (2) showed
      the most favorable antimicrobial activity with MICs of 45.2, 1.6, 2.8, 3.4, and
      47.5 microg/mL against B. subtilis, E. coli, P. fluorescence, S. aureus and A.
      niger, respectively.

PMID- 17194510
TI  - 222Rn and 220Rn concentrations in soil gas of Karkonosze-Izera Block (Sudetes,
      Poland).
AB  - Soil gas 222Rn and 220Rn concentrations were measured at 18 locations in the
      Karkonosze-Izera Block area in southwestern Poland. Measurements were carried out
      in surface air and at sampling depths of 10, 40 and 80 cm. Surface air 222Rn
      concentrations ranged from 4 to 2160 Bq m(-3) and 220Rn ranged from 4 to 228 Bq
      m(-3). The concentrations for 10 and 40 cm varied from 142 Bq m(-3) to 801 kBq m(
      3) and 102 Bq m(-3) to 64 kBq m(-3) for 222Rn and 220Rn, respectively. At 80 cm
      222Rn concentrations ranged from 94 Bq m(-3) to >1 MBq m(-3). The 220Rn
      concentrations at 80 cm varied from 45 Bq m(-3) to 48 kBq m(-3). The
      concentration versus depth profiles for 222Rn differed for soils developed on
      fault zones, uranium deposits or both. Atmospheric air temperature and soil gas
      222Rn and 220Rn were negatively correlated. At sampling sites with steep slopes,
      220Rn concentrations decreased with depth.

PMID- 17194509
TI  - Oral inoculation with Type III secretion mutants of Yersinia pseudotuberculosis
      provides protection from oral, intraperitoneal, or intranasal challenge with
      virulent Yersinia.
AB  - The enteric pathogen Yersinia pseudotuberculosis (Yptb) causes gastroenteritis,
      mesenteric lymphadenitis, and systemic infections in humans, livestock, and wild
      animals. Yptb Type III secretion system (pTTSS) mutants efficiently colonize
      lymphoid tissues, but not the gastrointestinal tract, spleen, or liver. Here, we
      show that a single oral inoculation of pTTSS mutants prevents morbidity in almost
      100% of mice challenged intragastrically with virulent Yptb. In addition, a
      single oral inoculation of a pTTSS mutant protected 50% of mice challenged
      intraperitoneally or intranasally with virulent Yptb. In addition, the
      intranasally challenged mice that succumbed to infection lived significantly
      longer than non-immunized mice. Thus, pTTSS mutants can function as live
      attenuated vaccine when delivered orally. Potential uses for these attenuated
      strains include use as a livestock vaccine, a rodent plague control reagent in
      endemic areas around the world, and a vector for delivery of other antigens to
      the mesenteric lymph nodes.

PMID- 17194511
TI  - Survey of fellows regarding a national study into treatment with hyperbaric
      oxygen.

PMID- 17194512
TI  - Perils of football goalkeepers.

PMID- 17194513
TI  - Health effects classification and its role in the derivation of minimal risk
      levels: immunological effects.
AB  - The Agency for Toxic Substances and Disease Registry (ATSDR) derives health-based
      guidance values known as minimal risk levels (MRLs). By definition, an MRL is a
      substance-specific estimate of the daily human exposure to a substance that is
      likely to be without an appreciable risk of adverse, noncancer effects over a
      specified duration of exposure. MRLs are preferentially derived from human
      studies, if available, or from the most sensitive animal species and the endpoint
      that is most relevant for humans. To date, the agency has derived 346 MRLs.
      Fifteen MRLs were derived for 11 different chemicals where the database has
      identified the immune system as the most sensitive target of toxicity. The
      chemicals include benzene, chlorfenvinphos, endosulfan, heptachlor, gamma
      hexachlorocyclohexane, dibutyl tin, tributyl tin, PCBs, 2,3,4,7,8
      pentachlorodibenzofuran, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and 2,4
      dichlorophenol. The agency's rationale for classification of immunological
      endpoints is discussed and a brief description given of the critical studies
      selected for MRL development using immune system endpoints.

PMID- 17194514
TI  - Gender and health care utilization: the role of mental distress and help-seeking
      propensity.
AB  - Many studies report higher levels of health care utilization among women.
      Understanding how gender influences health care utilization is still unresolved.
      We developed a model that could explain these gender-related differences. The
      possible pathways assumed by this model that relate gender to utilization, can be
      summarized as follows: (1) utilization may be influenced by somatic morbidity,
      mental distress, perceived symptoms, poor subjective health and propensity to use
      services; (2) women have higher levels of these variables than men (mediating
      effect); and (3) the direct effects of some of these variables on utililization
      are moderated by gender, i.e. they are stronger for women than for men
      (moderating effect). Data were drawn from a community-based sample of adult
      enrollees of a sickness fund in the Netherlands, who had responded to a mailed
      health survey (N = 8698). This survey contained questions on somatic morbidity,
      mental distress and other mediating variables. Health care utilization was
      measured prospectively, using data extracted from a claims database held by the
      sickness fund that covers all types of general health services except general
      practitioner consultations. The model was tested using structural equation
      modelling. Women reported more somatic morbidity and mental distress than men
      did, as well as elevated levels of other mediating variables, which might explain
      at least partly-gender related differences in utilization. Differences in
      propensity to use services were not found. The expected moderating effect of
      gender could not be demonstrated. That is, we did not find gender related
      differences in the strength of the relations between mental distress, other
      mediating variables and utilization. Mental distress is related to utilization in
      a way that is not gender specific, however, because women report higher levels of
      mental distress (as well as somatic morbidity), this results in a greater
      utilization of somatic health care services.

PMID- 17194515
TI  - The impact of disability transitions on social inclusion.
AB  - As the extent of disability increases in society, there is an increasing need to
      understand its consequences for many aspects of social inclusion. Using the
      Living in Ireland Survey 1995-2001 (n=2727 adults), we provide a rigorous
      analysis of the transitions into and out of disability and the related
      consequences for various characteristics of social inclusion. We compare the
      effect of onset, exit and persistent disability on household income and the
      probability of being in poverty. We also look at the impact on daily societal
      participation for individuals with varying durations of disability. Results show
      that people with disabilities have much lower levels of social inclusion and
      imply that related policy should focus on the heterogeneity of disabled people,
      depending on their respective transitions into disability and the duration of
      their disability.

PMID- 17194516
TI  - Differential response related to genotoxicity between eggplant (Solanum
      melanogena) skin aqueous extract and its main purified anthocyanin (delphinidin)
      in vivo.
AB  - Anthocyanins are the largest group of water-soluble pigments in the plant
      kingdom. A number of studies have demonstrated that anthocyanins present
      antioxidant capacity and show inhibitory effects on the growth of some cancer
      cells. Thus, the goal of this study was to evaluate both the
      antimutagenicity/antigenotoxicity and mutagenicity/genotoxicity of aqueous
      extract obtained from the Solanum melanogena, a possible novel source of
      anthocyanin, and its main purified anthocyanin extract (delphinidin), using the
      single cell (comet) assay and micronucleus test. Pretreatment with higher doses
      of the purified anthocyanin (10 and 20mg/kg b.w.) led to a statistically
      significant reduction (p<0.05) in the frequency of micronuclei in polychromatic
      erythrocytes induced by cyclophosphamide. The pattern of reduction ranged from
      48% to 57% independent of concentration. No apparent genotoxicity and
      mutagenicity was found for either the anthocyanin or delphinidin extracts. Taken
      together, these results suggest that mice pre-treated with specific compounds
      present in anthocyanins (delphinidin) displayed a lower incidence of mutations
      induced by cyclophosphamide. This finding emphasizes the potential of natural
      colorants to prevent mutations and also the applicability of genotoxic evaluation
      for improving health. Furthermore, the results presented here could be an
      additional argument to support the use of anthocyanins in the diet.

PMID- 17194519
TI  - Emergency medicine training for Croatia: a Croatia-Australia partnership.
AB  - As part of a health system improvement project, the Republic of Croatia has been
      conducting a pilot project aimed at rationalizing care delivery across the
      primary care, hospital and secondary care systems. One component was the
      development of an emergency department at Dr T Bardek Hospital in Koprivnica and
      training of its staff. This paper describes how a training programme was
      conducted, using an established emergency department in Australia as the training
      host, and the outcome of the project. This type of training programme could form
      a model for specialist Emergency Medicine training in the future.

PMID- 17194518
TI  - Expression changes of apoptotic-related proteins in nerve tissues of rats treated
      with allyl chloride.
AB  - Allyl chloride (AC) is widely used in industries as raw material and has been
      reported to produce occupational peripheral neuropathies in man chronically
      exposure to it. Although many studies have been done addressing to it, the
      mechanisms still remain unclear. To elucidate the molecular mechanism of
      neuropathy induced by AC, we measured the contents of glutathione (GSH), Bcl-2,
      Bax, cytochrome c (CytC) and Caspase-3 in a time-dependent manner by biochemical
      and quantitative immunoblotting techniques in rats' cerebrum and spinal cord
      after 3, 6, 9 and 12 weeks of AC intoxication. The results showed that the levels
      of Bcl-2 of cerebrum and spinal cord significantly (P<0.05) decreased after 9 and
      6 weeks of AC intoxication, respectively, while GSH levels decreased after 12
      week. However, the levels of Bax, CytC and Caspase-3 significantly (P<0.05)
      increased both in cerebrum and spinal cord. Bax levels of cerebrum and spinal
      cord increased after 12 and 9 weeks of AC administration, respectively. The
      levels of CytC and Caspase-3 also went up after 9 weeks of AC treatment in
      cerebrum and 9, 6 weeks in spinal cord, respectively. Thus, subchronic exposure
      to AC affected the expressions of apoptotic-related proteins in the central
      nervous system (CNS) and peripheral nervous system (PNS) tissues and the time
      dependent changes of these indexes occurred. The regulatory mechanism of
      apoptosis might be involved and served as one of mechanisms of toxic neuropathy
      induced by AC.

PMID- 17194517
TI  - Sensitivity of butyrylcholinesterase knockout mice to (--)-huperzine A and
      donepezil suggests humans with butyrylcholinesterase deficiency may not tolerate
      these Alzheimer's disease drugs and indicates butyrylcholinesterase function in
      neurotransmission.
AB  - Butyrylcholinesterase (EC 3.1.1.8 BChE) is present in all human and mouse
      tissues, and is more abundant than acetylcholinesterase (EC 3.1.1.7 AChE) in all
      tissues except brain. People who have no BChE activity due to a genetic variation
      are healthy. This has led to the hypothesis that BChE has no physiological
      function. We tested this hypothesis by challenging BChE and AChE knockout mice,
      as well as wild-type mice, with the AChE specific inhibitors, (--)-huperzine A
      and donepezil, and with serine hydrolase inhibitors, echothiophate and
      chlorpyrifos oxon. (--)-Huperzine A and donepezil caused mortality and
      significant toxicity in the BChE-/- animals. The BChE heterozygote (BCHE+/-) mice
      with approximately one-half the BChE activity of the BChE wild type (BChE+/+)
      exhibited intermediate toxic symptoms, and survived a longer period. The BChE+/+
      animals displayed comparatively minor toxic symptoms and recovered by 24h post
      dosing. Plasma AChE activity was inhibited to the same extent in BChE-/-, +/-,
      and +/+ mice, whereas BChE activity was not inhibited. This indicated that the
      protective effect of BChE was not due to scavenging (--)-huperzine A. AChE-/-
      mice were unaffected by (--)-huperzine A and donepezil, demonstrating the
      specificity of these inhibitors for AChE. AChE-/- mice treated with chlorpyrifos
      oxon lost all BChE activity, had severe cholinergic symptoms and died of
      convulsions. This showed that BChE activity was essential for survival of AChE-/-
      mice. In conclusion, we propose that the protective effect of BChE is explained
      by hydrolysis of excess acetylcholine in physiologically relevant regions such as
      diaphragm, cardiac muscle, and brain. Thus, BChE has a function in
      neurotransmission. People with BChE deficiency are expected to be intolerant of
      standard doses of the anti-Alzheimer's drugs, (--)-huperzine A and donepezil.

PMID- 17194520
TI  - Acute stress reactions in the first 3 weeks postpartum: a study of 219
      parturients.
AB  - OBJECTIVES: There is increasing research on posttraumatic stress (PS) 4-6 weeks
      and 3 months postpartum, but, there are no data on acute stress reactions (ASR)
      in the first 3 weeks postpartum, i.e. the potential precursors of PS. However,
      ASR may have long-term effects, e.g., on a subsequent pregnancy without having
      manifested as PS in the meantime. We propose: (i) to describe the patterns of ASR
      after childbirth, (ii) to explore differences between women with normal and
      traumatogenic ASR, and (iii) to provide data on the early detection of
      traumatogenic ASR 2 and 3 weeks postpartum. STUDY DESIGN: Intra-event variables
      (relationship with caregivers, overall birth experience, and dissociative
      experiences, as well as obstetric variables) were assessed 48-96 h. postpartum,
      as were ASR (by means of the Impact-of-Event Scale IES) in weeks 1, 2, and 3
      postpartum. According to research on PS the upper 33%-range of ASR in weeks 2 and
      3 was defined as 'traumatogenic'. RESULTS: Normal ASR in week 1 are at a level
      which in non-obstetric trauma-situations is considered as the upper range of low
      stress or lower range of medium distress. ASR decline constantly from week 1 to
      week 3. However, high ASR in week 1 do not drop faster than do low ones, thus
      indicating a prolonged stress reaction in women with high ASR in week 1. Low ASR
      (IES-scores <10) and high ASR (IES-scores >20) in week 1 are highly predictive
      for normal ASR, and traumatogenic ASR in weeks 2 and 3, respectively. Medium ASR
      (IES-scores 10-20) in week 1 are of uncertain predictive value for stress
      reactions in weeks 2 and 3 and have to be re-assessed at that time. CONCLUSIONS:
      Clinical screening for ASR appears to be helpful in detecting women with a
      compromised ability to process childbirth-related stress. The association between
      ASR and long-term development should be further explored.

PMID- 17194521
TI  - Hemodynamic changes in the fetal arteries during the second half of pregnancy
      assessed by Doppler velocimetry.
AB  - The applicability of Doppler velocimetry has been well established regarding
      intrauterine growth restriction and fetal hypoxia. This method can also be used
      to determine fetal anemia and cardiac malformations. The main fetal arteries
      evaluated by Doppler velocimetry are the middle cerebral artery and the umbilical
      artery. However, the fetal aorta is responsible for the distribution of blood
      flow to the upper and lower extremities of the human body and should also be
      properly valued. In order to characterize abnormalities in the arteries of high
      risk fetuses, it is necessary to know the hemodynamic modifications of normal
      fetuses. On this basis, the authors performed a review of fetal hemodynamics
      evaluated by Doppler velocimetry in the fetal aorta and middle cerebral and
      umbilical arteries during the second half of pregnancy. The study of fetal
      vessels by Doppler velocimetry indirectly evaluates the hemodynamic changes
      occurring in fetuses at risk. In this respect, we emphasize the changes in
      Doppler velocimetry occurring in fetal anemia, in restricted intrauterine growth,
      and in normal fetuses.

PMID- 17194522
TI  - Application of surface molecular imprinting adsorbent in expanded bed for the
      adsorption of Ni(2+) and adsorption model.
AB  - A new surface molecular imprinting adsorbent (SMIA) was used in an expanded bed.
      The expansion ratio and adsorption performance were studied at different
      volumetric rates, inlet concentrations, and pH values. A model based on the Adams
      Bohart adsorption model of breakthrough curves was established. The predicted
      curves had good agreement with the experimental curves. The breakthrough time
      (T(1/2)) decreased with increasing inlet concentration when the outlet
      concentration was half the initial concentration (C/C(0)=0.5). The inlet
      concentration had little effect on the adsorption rate constant (k(1)) value when
      the initial concentration (C(0)) was above 150 mg/L. However, T(1/2) values
      increased with increasing initial pH of the inlet solution, and the k(1) value
      decreased due to the competition between H(+) and Ni(2+).

PMID- 17194524
TI  - The genotypic complexity of evolved fault-tolerant and noise-robust circuits.
AB  - Noise and component failure is an increasingly difficult problem in modern
      electronic design. Bio-inspired techniques is one approach that is applied in an
      effort to solve such issues, motivated by the strong robustness and adaptivity
      often observed in nature. Circuits investigated herein are designed to be
      tolerant to faults or robust to noise, using an evolutionary algorithm. A major
      challenge is to improve the scalability of the approach. Earlier results have
      indicated that the evolved circuits may be suited for the application of
      artificial development, an approach to indirect mapping from genotype to
      phenotype that may improve scalability. Those observations were based on the
      genotypic complexity of evolved circuits. Herein, we measure the genotypic
      complexity of circuits evolved for tolerance to faults or noise, in order to
      uncover how that tolerance affects the complexity of the circuits. The complexity
      is analysed and discussed with regards to how it relates to the potential
      benefits to the evolutionary process of introducing an indirect genotype
      phenotype mapping such as artificial development.

PMID- 17194523
TI  - Role of toxin and nutrient for the occurrence and termination of plankton bloom-
      results drawn from field observations and a mathematical model.
AB  - The termination of harmful algal blooms (HABs) and coexistence of phytoplankton
      zooplankton populations are of great importance to human health, ecosystem,
      environment, tourism and fisheries. In this paper we propose a three-component
      model consisting of dissolved limiting nutrients (N) supplied at constant rate
      and partially recycled after the death of plankton by bacterial decomposition,
      phytoplankton (P) and zooplankton (Z), where the growth of zooplankton species
      reduce due to toxic chemicals released by phytoplankton species. Our analysis
      leads to different thresholds which are expressible in terms of model parameters
      and determine the existence and stability of various states of the system. We
      observe that phytoplankton-zooplankton persist if the maximal zooplankton
      ingestion rate exceeds a lower threshold value. It is shown that the coexistence
      equilibrium loses its stability when the dilution rate of the nutrient
      concentration passes through a critical value and Hopf bifurcation occurs that
      induces oscillations of the population. Our results indicate that the occurrence
      of bloom increases when the nutrient concentration is very high, and in that case
      toxin produced by the phytoplankton plays a very crucial role towards the
      termination of the planktonic bloom.

PMID- 17194525
TI  - Evidence for transmitter operated electrical synapses (TOES) in ampullary
      electroreceptor organs.
AB  - Afferent fibres of ampullary electroreceptor organs in electrosensitive fish fire
      spontaneously, that is, they fire without external stimulus. In the past it has
      been postulated that the spontaneous activity originates from a sustained level
      of neurotransmitter release delivered by the electroreceptor cells. The
      spontaneous activity can be modulated by electrical stimuli. Blocking of the
      chemical synapse, however, reduces the susceptibility to electrical stimuli to 2%
      or less, but the spontaneous activity to 60% only. By evaluating existing
      experimental evidence it is concluded that spontaneous firing of afferents is
      based on two processes. (1) A membrane bound oscillator, which does not depend on
      transmitter release, is almost free of frequency fluctuations, and is described
      by Hodgkin/Huxley-equations (HH-equations). (2) Release of neurotransmitter,
      which increases the firing level, adds frequency noise, and raises the
      susceptibility of the afferent to electrical stimuli. There is evidence that
      neurotransmitter release acts as a gating process, which makes the generator area
      of the afferents directly accessible to electrical stimuli from the outside.
      Apparently, the activated synapse behaves as a transmitter operated electrical
      synapse (TOES).

PMID- 17194527
TI  - The promoter of the rat 5alpha-reductase type 1 gene is bidirectional and Sp1
      dependent.
AB  - In many androgen target tissues, testosterone is reduced to the more potent
      androgen, dihydrotestosterone, by steroid 5alpha-reductase. Two isoforms of
      5alpha-reductase, type 1 and type 2, have been cloned. They are differentially
      expressed and regulated. To determine the mechanisms of regulation of 5alpha
      reductase type 1 expression, we have cloned its 5'upstream region and defined its
      promoter. The proximal 5'upstream region of 5alpha-reductase type 1 displays all
      the features of a CpG island and has numerous Sp1 binding sites. By transient
      transfection assays, we have identified a bidirectional promoter activity in this
      region; this activity was highest in the negative orientation, in the direction
      of the methyltransferase Nsun2 (predicted) gene. Promoter activity, in either
      orientation, was lost in Sp1 deficient cells but was rescued following co
      transfection with a Sp1 expression vector. Thus, the 5'upstream region of rat
      5alpha-reductase type 1 contains a bidirectional promoter with an activity that
      is Sp1-dependent.

PMID- 17194528
TI  - Ginkgo biloba and ovarian cancer prevention: epidemiological and biological
      evidence.
AB  - There is considerable interest in herbal therapies for cancer prevention but
      often with little scientific evidence to support their use. In this study, we
      examined epidemiological data regarding effects of commonly used herbal
      supplements on risk for ovarian cancer and sought supporting biological evidence.
      4.2% of 721 controls compared to 1.6% of 668 cases regularly used Ginkgo biloba
      for an estimated relative risk (and 95% confidence interval) of 0.41 (0.20,0.84)
      (p=0.01); and the effect was most apparent in women with non-mucinous types of
      ovarian cancer, RR=0.33 (0.15,0.74) (p=0.007). In vitro experiments with normal
      and ovarian cancer cells showed that Ginkgo extract and its components, quercetin
      and ginkgolide A and B, have significant anti-proliferative effects (
      approximately 40%) in serous ovarian cancer cells, but little effect in mucinous
      (RMUG-L) cells. For the ginkgolides, the inhibitory effect appeared to be cell
      cycle blockage at G0/G1 to S phase. This combined epidemiological and biological
      data provide supportive evidence for further studies of the chemopreventive or
      therapeutic effects of Ginkgo and ginkgolides on ovarian cancer.

PMID- 17194529
TI  - Expression of GAGE family proteins in malignant melanoma.
AB  - Cancer/testis antigens are considered as promising targets for immunotherapy
      against tumors including malignant melanoma. One group of these antigens is the
      GAGE antigen family. In this study, we obtained recombinant GAGE-7b protein
      against which a rabbit antiserum was generated. The polyclonal, monospecific
      antibodies were used to analyze the expression of GAGE family proteins in human
      melanoma tissues and cell lines. GAGE expression in melanoma cell lines ranged
      from 41% to 58% and in melanoma tissues from 22% to 53%. Immunohistochemical
      analysis of melanoma tumors revealed a rather heterogeneous expression of GAGE
      resulting in individual positive cells or foci of stained cells. Furthermore, we
      could show that autoantibodies against GAGE family proteins are detectable in 6%
      of melanoma patients. Besides, we first demonstrated that the expression of GAGE
      family proteins can be stimulated with 5'-aza-2'-deoxycytidine and trichostatin
      A. Through upregulation of protein expression GAGE family proteins might develop
      into promising targets for immunotherapy of melanoma and other tumors.

PMID- 17194530
TI  - Use of active consortia of constructed ternary bacterial cultures via mixture
      design for azo-dye decolorization enhancement.
AB  - This first-attempt study used constructed bacterial consortia containing
      Escherichia coli DH5alpha (a weak decolorizer) and its UV-irradiated mutants (E.
      coli UVT1 and UV68; strong decolorizers) via equilateral triangle diagram and
      mixture experimental design to assess color removal during species evolution. The
      results showed that although strain DH5alpha was not an effective decolorizer,
      its presence might still played a significant role in affecting optimal color
      removal capabilities of mixed consortia (e.g., E. coli DH5alpha, UVT1 and UV68)
      for two model azo dyes; namely, reactive red 22 (RR22) and reactive black 5
      (RB5). Contour analysis of ternary systems also clearly showed that
      decolorization of RR22 and RB5 by DH5alpha-containing active mixed consortia was
      more effective than mono-cultures of the stronger decolorizer alone (e.g., UVT1).
      The optimal composition of the mixed consortium (UV68, UVT1, DH5alpha) achieving
      the highest specific decolorization rate was (13%:58%:29%) and (0%:74%:26%) for
      decolorization of RR22 and RB5, respectively, with initial total cell density
      fixed at OD(600)=3.5+/-0.28.

PMID- 17194531
TI  - Dust explosions-cases, causes, consequences, and control.
AB  - Dust explosions pose the most serious and widespread of explosion hazards in the
      process industry alongside vapour cloud explosions (VCE) and boiling liquid
      expanding vapour explosions (BLEVE). Dust explosions almost always lead to
      serious financial losses in terms of damage to facilities and down time. They
      also often cause serious injuries to personnel, and fatalities. We present the
      gist of the dust explosion state-of-the-art. Illustrative case studies and past
      accident analyses reflect the high frequency, geographic spread, and damage
      potential of dust explosions across the world. The sources and triggers of dust
      explosions, and the measures with which different factors associated with dust
      explosions can be quantified are reviewed alongside dust explosion mechanism. The
      rest of the review is focused on the ways available to prevent dust explosion,
      and on cushioning the impact of a dust explosion by venting when the accident
      does take place.

PMID- 17194532
TI  - Investigation kinetics mechanisms of adsorption malachite green onto activated
      carbon.
AB  - Lignite was used to prepare activated carbon (T3K618) by chemical activation with
      KOH. Pore properties of the activated carbon such as BET surface area, pore
      volume, pore size distribution, and pore diameter were characterized by t-plot
      based on N2 adsorption isotherm. BET surface area of activated carbon is
      determined as 1000 m2/g. Adsorption capacity of malachite green (MG) onto T3K618
      activated carbon was investigated in a batch system by considering the effects of
      various parameters like initial concentration (100, 150 and 200 mg/L) and
      temperature (25, 40 and 50 degrees C). The adsorption process was relatively fast
      and equilibrium was reached after about 20 min for 100, 150 mg/L at all
      adsorption temperature. Equilibrium time for 200 mg/L was determined as 20 min
      and 40 min at 298, 313 and 323 K, respectively. Simple mass and kinetic models
      were applied to the experimental data to examine the mechanisms of adsorption and
      potential rate controlling steps such as external mass transfer, intraparticle
      diffusion. Pseudo second-order model was found to explain the kinetics of MG
      adsorption most effectively. It was found that both mass transfer and pore
      diffusion are important in determining the adsorption rates. The intraparticle
      diffusion rate constant, external mass transfer coefficient, film and pore
      diffusion coefficient at various temperatures were evaluated. The activation
      energy (Ea) was determined as 48.56, 63.16, 67.93 kJ/mol for 100, 150, 200 mg/L,
      respectively. The Langmiur and Freundlich isotherm were used to describe the
      adsorption equilibrium studies at different temperatures. Langmiur isotherm shows
      better fit than Freundlich isotherm in the temperature range studied. The
      thermodynamic parameters, such as DeltaG degrees, DeltaS and DeltaH degrees were
      calculated. The thermodynamics of dyes-T3K618 system indicates endothermic
      process.

PMID- 17194533
TI  - Treatment of waste printed wire boards in electronic waste for safe disposal.
AB  - The printed wire boards (PWBs) in electronic waste (E-waste) have been found to
      contain large amounts of toxic substances. Studies have concluded that the waste
      PWBs are hazardous wastes because they fails the toxicity characteristic leaching
      procedure (TCLP) test with high level of lead (Pb) leaching out. In this study,
      two treatment methods - high-pressure compaction and cement solidification - were
      explored for rendering the PWBs into non-hazardous forms so that they may be
      safely disposed or used. The high-pressure compaction method could turn the PWBs
      into high-density compacts with significant volume reduction, but the impact
      resistance of the compacts was too low to keep them intact in the environment for
      a long run. In contrast, the cement solidification could turn the PWBs into
      strong monoliths with high impact resistance and relatively high compressive
      strength. The leaching of the toxic heavy metal Pb from the solidified samples
      was evaluated by both a dynamic leaching test and the TCLP test. The dynamic
      leaching results revealed that Pb could be effectively confined in the solidified
      products under very harsh environmental conditions. The TCLP test results showed
      that the leaching level of Pb was far below the regulatory level of 5mg/L,
      suggesting that the solidified PWBs are no longer hazardous. It was concluded
      that the cement solidification is an effective way to render the waste PWBs into
      environmentally benign forms so that they can be disposed of as ordinary solid
      wastes or beneficially used in the place of concrete in some applications.

PMID- 17194534
TI  - Investigations of sequential leaching behaviour of Cu and Zn from coal fly ash
      and their mobility in environmental conditions.
AB  - The quantitative evaluation of chemical fraction of Cu and Zn in the coal fly ash
      by methods of five-step sequential extraction was carried out in order to
      characterize metal mobility in environmental conditions. The research involved
      (i) water-soluble (pH 7), (ii) acid-soluble (pH 5), (iii) oxide, (iv) difficult
      reducible and (v) residual metal fractions. It was discovered, that the total
      extraction of the studied metals from coal fly ash to solutions take place in the
      following quantities Cu-39.0mgkg(-1) and Zn-89.0mgkg(-1). The investigations of
      chemical fractions proved that the subject metals occur mainly in coal fly ash
      as: oxide (Cu-12.0mgkg(-1), Zn-37.0mgkg(-1)) and residual (Cu-9.5mgkg(-1), Zn
      27.0mgkg(-1)) as well as difficult reducible (Cu-16.5mgkg(-1), Zn-22.0mgkg(-1)).
      Low concentrations of metals for water-soluble fraction (Cu<d.l., Zn-0.5mgkg(-1))
      and acid-soluble fraction (Cu-1.0mgkg(-1), Zn-2.5mgkg(-1)) were observed. The
      fractions of Cu and Zn leachable from the ash in environmental conditions
      contain: 2.6% (Cu) and 3.4% (Zn) of metal total amount in the coal fly ash. The
      obtained mobility parameter of Cu and Zn can be applied to estimate the
      concentration increase of mobile and hardly mobile forms of these metals in soil
      polluted with the ash.

PMID- 17194535
TI  - Integrated treatment scheme for rubber thread wastewater: sulfide precipitation
      and biological processes.
AB  - In this study, acidic latex wastewater containing high average zinc and acetic
      contents of 816mgL(-1) and 20,862mgCODL(-1), respectively, was treated
      successfully by a series of chemical and biological processes without any
      addition of acid or base for pH adjustment. Total dissolved solids of the treated
      effluent increased by only 1.1-fold on average for sulfide precipitation as
      compared to 2.8-fold for the hydroxide strategy. The oxidation-reduction
      potential (ORP) value of 0mV was used successfully as an indicator for optimum
      sulfide addition which consistently provided an appreciable reduction in effluent
      concentrations to less than 1 and 2mgL(-1) for zinc and residual sulfide,
      respectively. The anaerobic filter was very stable in handling the chemically
      treated wastewater up to the organic loading rate of 11.8gCODL(-1)day(-1) with an
      average efficiency of 92%. Methane production and biomass yield were
      0.32L(gCOD(removed))(-1) and 0.014gVSS (gCOD(removed))(-1), respectively. For the
      activated sludge process, the optimum sludge age and hydraulic retention time
      were 30 and 0.8 days, respectively, which are equivalent to the organic loading
      rates of 2.50gCODL(-1)day(-1) or 2.13gBODL(-1)day(-1). Under these optimum
      conditions, average removal efficiencies for COD and BOD were 96.6 and 99.4%.
      Average soluble COD, BOD and suspended solids in the effluent were 71, 11 and
      38mgL(-1), respectively. This integrated treatment scheme was proven to be an
      effective approach for highly polluted and toxic rubber thread wastewater.

PMID- 17194536
TI  - Prazosin increases immobility episodes in taiep rats without changes in the
      properties of alpha1 receptors.
AB  - The taiep rat is a myelin mutant in which immobility episodes (IEs) can be
      induced in adult males by gripping. EEG recordings during gripping-induced IEs
      show a rapid eye movement (REM) sleep-like pattern, similar to that reported for
      narcolepsy-cataplexy suggesting that IEs represent a disorder of REM-sleep. An
      alpha(2) adrenoceptor agonist increases gripping-induced IEs, whereas alpha(2)
      antagonists decrease these. We have studied the effect of prazosin on IEs and the
      levels of alpha(1) adrenoceptors were evaluated in cerebro-cortical homogenates
      of taiep and control rats. Systemic administration of prazosin results in a
      significant increase in both the frequency and duration of gripping-induced IEs.
      Our results show that cerebro-cortical tissue is not an adequate candidate for
      the expression of cataplexy-like symptoms, but prazosin, an alpha(1) antagonist,
      is a potent inducer of gripping-induced immobility episodes in taiep rats.

PMID- 17194537
TI  - Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of
      patients with idiopathic normal pressure hydrocephalus.
AB  - We investigated cerebrospinal fluid (CSF) samples from 21 patients with
      idiopathic normal pressure hydrocephalus (INPH) and 14 controls without
      neurological disease. The concentrations of leucine-rich alpha-2-glycoprotein
      (LRG), transforming growth factor (TGF)-beta1, 2, 3 and TGF-beta type II receptor
      (TbetaR-II) in CSF were measured using ELISA. TGF-beta1, TbetaR-II and LRG CSF
      levels of patients with INPH were significantly higher than controls, whereas no
      significant differences in TGF-beta2 levels were found between INPH patients and
      controls. The present study suggests that TGF-betas expressions may be modulated
      differently in patients with INPH. These results also indicate that the CSF level
      assay of TGF-beta1, TbetaR-II and LRG is useful for the diagnosis of patients
      with INPH, and TGF-beta1, TbetaR-II and LRG may be involved in the pathogenesis
      of the disease.

PMID- 17194539
TI  - Anticipation of elbow joint perturbation shortens the onset time of the reflex
      EMG response in biceps brachii and triceps brachii.
AB  - This study aimed to investigate the influence of the anticipation of a
      perturbation torque applied to extend the elbow joint on the onset time of reflex
      electromyogram (EMG) responses. A perturbation torque generated by an
      electromagnetic torque motor system was applied to the forearm of eleven subjects
      during trials. The trials were divided into an anticipated (AN) condition -
      perturbation torque applied after the auditory signal - and an unanticipated
      (UAN) condition - suddenly applied perturbation. To detect the reflex EMG
      response in the biceps brachii (Bb) and triceps brachii (Tb) muscles, a new
      method involving the discrete wavelet transform and outlier tests was used. We
      found that the onset time of the reflex response in both the muscles in the AN
      condition was significantly shorter than that in the UAN condition. The angle of
      transition from flexion to extension, which was induced by the reflex response of
      Bb, was also significantly smaller in the AN condition than in the UAN condition.
      The results indicate that the anticipation of an applied perturbation torque
      decreases the onset time of the reflex response in the Bb and Tb.

PMID- 17194538
TI  - RNA interference-mediated inhibition of brain-derived neurotrophic factor
      expression increases cocaine's cytotoxicity in cultured cells.
AB  - Previous studies showed that cocaine exposure decreased brain-derived
      neurotrophic factor (BDNF) function and resulted in neuronal cell death. To
      investigate a role of BDNF in cocaine's cytotoxicity, an RNA interference (RNAi)
      approach was used. Transfection of neuroblastoma SK-N-AS cells or primary rat
      hippocampal neurons with the small double-stranded interfering RNA (siRNA)
      targeting BDNF mRNA, but not the scrambled siRNA, resulted in reductions in
      levels of BDNF mRNA and proteins by more than 70% in the transfected cells as
      compared with the control group, suggesting an RNAi-mediated, sequence-specific
      gene silencing. The results also showed that cocaine-induced cytotoxicity,
      assessed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazodium
      bromide) assay, was more pronounced in the cells transfected with the siRNA than
      in the cells transfected with the scrambled siRNA or in the cells treated with
      Lipofectamine 2000 alone (the control group), suggesting that inhibition of BDNF
      expression enhances cocaine's cytotoxicity. Together with previous studies
      showing that cocaine suppresses BDNF expression, the present data suggest that
      the drug-induced reduction of BDNF productions may make neurons more vulnerable
      to cocaine's toxic effects and precipitate cocaine-induced central nervous system
      damages.

PMID- 17194540
TI  - Microglial cells and peritoneal macrophages release activin A upon stimulation
      with Toll-like receptor agonists.
AB  - Activin A levels are elevated in the cerebrospinal fluid (CSF) of patients with
      meningitis and in the sera of patients with sepsis. The source(s) of the elevated
      concentrations of activin A in CSF and serum have not yet been discovered. Here
      we demonstrate that primary mouse microglial cells and peritoneal macrophages
      release activin A after treatment with agonists of Toll-like receptor (TLR) 2, 4,
      and 9. These findings provide further evidence for a role of activin in the
      innate immune response and suggest that microglial cells and macrophages are a
      source of elevated activin A concentrations observed in the CSF during bacterial
      meningitis and in the systemic circulation during sepsis.

PMID- 17194541
TI  - A polymorphism of LOC387715 gene is associated with age-related macular
      degeneration in the Japanese population.
AB  - Age-related macular degeneration (AMD) is one of the leading causes of blindness
      among older adults in developed countries and also in Japan. Previous research
      suggests that AMD is etiologically a complex disease, caused by multiple genes
      and environmental factors. Association studies have identified that a complement
      factor H gene (CFH) variant is a major risk factor for AMD in Caucasians.
      However, we and two other groups have reported no association between CFH and AMD
      in the Japanese population. Recent studies have suggested that LOC387715 on
      chromosome 10q26 may be the second major risk loci for AMD in Caucasians. In this
      study, we examined the association between LOC387715 and AMD in Japanese, and our
      results show that polymorphism of the LOC387715 gene is associated with AMD in
      Japanese as well as in Caucasians. Our data show a disease odds ratio of 6.20
      (95% CI: 2.87-13.40) conferred by homozygosity for risk alleles at LOC387715
      compared with the non-risk genotype. A polymorphism of LOC387715 gene is
      associated with AMD in the Japanese population.

PMID- 17194542
TI  - Effect of CP55,940 on mechanosensory spinal neurons following chronic
      inflammation.
AB  - Cannabinoid receptor agonists have previously been shown to produce
      antinociceptive effects in rodent models of inflammatory pain. In the present
      study, we characterized responses of spinal dorsal horn neurons receiving sensory
      input from the hind paw in rats that had received intraplantar injection of
      complete Freund's adjuvant (CFA), and examined effects of the nonselective CB1/2
      receptor agonist CP55,940 on spinal neuron responses. Systemic (i.v.)
      administration of CP55,940 failed to attenuate responses of dorsal horn neurons
      to noxious mechanical stimulation in naive rats, but significantly reduced
      responses in CFA-inflamed rats to 25.78+/-13.7% of vehicle control at a
      cumulative dose of 0.8 mg/kg (ID50=0.28+/-0.02 mg/kg). Additionally, local
      administration of CP55,940 (10 microM) to the spinal cord reduced responses of
      mechanosensory dorsal horn neurons in CFA-inflamed rats to 67.15+/-7.1% of
      vehicle control. The inhibitory action of CP55,940 on spinal dorsal horn neurons
      in CFA-inflamed rats was mediated by CB1 receptors since local pretreatment with
      the CB1 receptor antagonist AM251 (10 microM) blocked this effect, while the CB2
      receptor antagonist AM630 (10 microM) was ineffective. Our results suggest that
      following inflammation, the inhibition of spinal nociceptive transmission by
      CP55,940 is mediated in part by spinal CB1 receptors, and not spinal CB2
      receptors.

PMID- 17194543
TI  - Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in
      Parkinson's disease.
AB  - GSTs are a family of inducible phase II enzymes that may play a neuroprotective
      role in Parkinson's disease (PD). GSTs may also modify PD risk by metabolizing
      compounds in cigarettes, as cigarette smoking is generally found to be associated
      with a decrease in PD risk. Using a population-based case-control study design,
      we examined polymorphisms of the mu, omega, pi, and theta classes of GST to
      elucidate the main effects and smoking-GST interactions on PD risk. From three
      rural California counties, we recruited 289 incident idiopathic PD cases,
      clinically confirmed by our study neurologist, and 270 population controls,
      marginally matched by age, gender, and race. We assessed main gene polymorphism
      associations and evaluated interactions between smoking and GST polymorphisms as
      departures from a multiplicative scale adjusting for age, gender, and race. We
      also restricted analyses to Caucasian subjects to address the potential for
      population stratification (n=235 cases, 220 controls). Among Caucasians, we
      observed a risk reduction in subjects carrying at least one variant allele for
      GSTO1 (OR=0.68, 95% CI: 0.47-0.98) and also GSTO2 (OR=0.64, 95% CI: 0.44-0.93);
      both genes were in strong linkage disequilibrium. No main gene effects were
      observed for the remaining polymorphisms. We noted a multiplicative interaction
      between ever having smoked regularly and GSTO1 (OR(interaction)=0.55, 95% CI:
      0.33-0.92) and GSTO2 (OR(interaction)=0.54, 95% CI: 0.32-0.90). Results were
      similar when combining all races. These findings and the paucity of similar
      studies suggest a need for further inquiry into the association between GSTs,
      smoking, and PD risk.

PMID- 17194544
TI  - Eye dominance predicts fMRI signals in human retinotopic cortex.
AB  - There have been many attempts to define eye dominance in normal subjects, but
      limited consensus exists, and relevant physiological data is scarce. In this
      study, we consider two different behavioral methods for assignment of eye
      dominance, and how well they predict fMRI signals evoked by monocular
      stimulation. Sighting eye dominance was assessed with two standard tests, the
      Porta Test, and a 'hole in hand' variation of the Miles Test. Acuity dominance
      was tested with a standard eye chart and with a computerized test of grating
      acuity. We found limited agreement between the sighting and acuity methods for
      assigning dominance in our individual subjects. We then compared the fMRI
      response generated by dominant eye stimulation to that generated by non-dominant
      eye, according to both methods, in 7 normal subjects. The stimulus consisted of a
      high contrast hemifield stimulus alternating with no stimulus in a blocked
      paradigm. In separate scans, we used standard techniques to label the borders of
      visual areas V1, V2, V3, VP, V4v, V3A, and MT. These regions of interest (ROIs)
      were used to analyze each visual area separately. We found that percent change in
      fMRI BOLD signal was stronger for the dominant eye as defined by the acuity
      method, and this effect was significant for areas located in the ventral
      occipital territory (V1v, V2v, VP, V4v). In contrast, assigning dominance based
      on sighting produced no significant interocular BOLD differences. We conclude
      that interocular BOLD differences in normal subjects exist, and may be predicted
      by acuity measures.

PMID- 17194547
TI  - Neospora caninum antibodies detected in Midwestern white-tailed deer (Odocoileus
      virginianus) by Western blot and ELISA.
AB  - White-tailed deer (Odocoileus virginianus) serve to maintain the Neospora caninum
      life cycle in the wild. Sera from white-tailed deer from south central Wisconsin
      and southeastern Missouri, USA were tested for antibodies to N. caninum by
      Western blot analyses and two indirect ELISAs. Seroreactivity against N. caninum
      surface antigens was observed in 30 of 147 (20%) of WI deer and 11 of 23 (48%) of
      MO deer using Western blot analysis. Compared to Western blot, the two indirect
      ELISAs were found to be uninformative due to degradation of the field-collected
      samples. The results indicate the existence of N. caninum antibodies in MO and WI
      deer, and that Western blot is superior to ELISA for serologic testing when using
      degraded blood samples collected from deer carcasses.

PMID- 17194546
TI  - Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic
      vasodilatation in human skin.
AB  - The effect of Botulinum Toxin type A (BoNT/A) on pain and neurogenic
      vasodilatation induced by application to the human skin of thermal stimuli and
      capsaicin was evaluated in a double blind study. A capsaicin cream (0.5 ml of a
      0.075%) was applied to the skin of both forearms of eighteen subjects randomly
      pretreated with either BoNT/A (Botox) or 0.9% saline (NS). Capsaicin was applied
      to a skin area either inside (protocol A) or adjacent to the BoNT/A treated area
      (protocol B). Pre-treatment with BoNT/A did not affect thermal-specific and
      thermal-pain thresholds (by quantitative sensory testing). However, capsaicin
      induced pain sensation (by a visual analogue scale), flare area (by acetate
      sheet) and changes in cutaneous blood flow (CBF, by laser Doppler flowmetry) were
      reduced when capsaicin was administered inside (protocol A) the BoNT/A treated
      area. In Protocol B, capsaicin-induced pain was unchanged, and capsaicin-induced
      flare/increase in CBF were reduced only in the area treated with BoNT/A, but not
      in the BoNT/A untreated area. Results indicate that (i) BoNT/A reduces capsaicin
      induced pain and neurogenic vasodilatation without affecting the transmission of
      thermal and thermal-pain modalities; (ii) reduction in capsaicin-induced pain
      occurs only if capsaicin is administered into the BoNT/A pretreated area; (iii)
      reduction in neurogenic vasodilatation by BoNT/A does not contribute to its
      analgesic action. BoNT/A could be tested for the treatment of conditions
      characterised by neurogenic inflammation and inflammatory pain.

PMID- 17194545
TI  - Ultrastructural evidence for co-localization of corticotropin-releasing factor
      receptor and mu-opioid receptor in the rat nucleus locus coeruleus.
AB  - Previous studies have shown that corticotropin-releasing factor (CRF), an
      integral mediator of the stress response, and opioids regulate the activity of
      the locus-coeruleus-norepinephrine (LC-NE) system during stress in a reciprocal
      manner. Furthermore, repeated opiate exposure sensitizes noradrenergic neurons to
      CRF. Previous studies have shown that mu-opioid receptors (muORs) are prominently
      distributed within somatodendritic processes of catecholaminergic neurons in the
      LC and axon terminals containing opioid peptides and CRF converge within the LC.
      To further examine cellular sites for interactions between CRF receptor type 1
      (CRFr) and muOR, immunofluorescence and electron microscopic analysis of the rat
      LC was conducted. Triple immunofluorescence showed prominent co-localization of
      the CRFr and muOR in noradrenergic somata in the LC. Ultrastructural analysis
      confirmed dual localization of CRFr and muOR in common dendritic processes in the
      LC. Semi-quantitative analysis showed that of the dendrites exhibiting CRFr
      immunolabeling, 57% expressed muOR immunoreactivity. These data provide
      ultrastructural evidence that CRFr and muOR are co-localized in LC neurons, a
      cellular substrate that may underlie opiate-induced sensitization of brain
      noradrenergic neurons to CRF.

PMID- 17194548
TI  - Response acquisition with delayed reinforcement in Lewis and Fischer 344 rats.
AB  - Previous work has shown neurochemical and behavioral differences between Lewis
      rats and Fischer 344 rats. Some of this work suggests that there might be
      differential sensitivity to delayed reinforcement between the two strains. To
      further explore this possibility, Lewis (n=8) and Fischer 344 (n=8) rats were
      exposed to a response-acquisition task with a non-resetting 20s delay to
      reinforcement. A tandem fixed-ratio 1, fixed-time 20s schedule of reinforcement
      was programmed for one of two levers; presses on the alternate lever had no
      programmed consequences. A greater number of Lewis rats (5/8) acquired lever
      pressing compared to the Fischer 344 rats (2/8). Future work with these strains
      may lead to a better understanding of the genetic and/or neurochemical factors
      involved in temporal control of behavior.

PMID- 17194549
TI  - Timing of omitted events: an analysis of temporal control of inhibitory behavior.
AB  - This paper reviews research designed to investigate the temporal control of
      inhibitory responding using rats as subjects. One area of investigation has
      focused on the role of temporal variables in conditioned inhibition produced
      using Pavlov's [Pavlov, I.P., 1927. Conditioned Reflexes. Oxford University
      Press, London, 430 pp.] procedure. These studies have found that evidence of
      conditioned inhibition obtained by negative summation testing is strongest when
      the conditioned inhibitor signals the omission of the unconditioned stimulus (US)
      at the same temporal location as a transfer excitor signals presentation of the
      US [e.g., Barnet, R.C., Miller, R.R., 1996. Temporal encoding as a determinant of
      inhibitory control. Learn. Motiv. 27, 73-91]. Similarly, retardation of
      acquisition of behavioral control by a previously inhibitory conditioned stimulus
      (CS) is maximal when the inhibitory CS is paired with the US at the same temporal
      location as the inhibitor had previously signaled US omission [Burger, D.,
      Denniston, J.C., Miller, R.R., 2001. Temporal coding in condition inhibition:
      retardation tests. Anim. Learn. Behav. 29, 281-290]. Other lines of research
      designed to assess the associative structure of temporal control of inhibition
      [e.g., Denniston, J.C., Blaisdell, A.P., Miller, R.R., 2004. Temporal control in
      conditioned inhibition: analysis of associative structure of inhibition. J. Exp.
      Psychol. Anim. Behav. Process. 30, 190-202] are reviewed, as is the assessment of
      temporal control of inhibition produced through extinction [Denniston, J.C.,
      Miller, R.R., 2003. The role of temporal variables in inhibition produced through
      extinction. Learn. Behav. 31, 35-48]. These collective observations are discussed
      in terms of the temporal coding hypothesis [Matzel, L.D., Held, F.P., Miller,
      R.R., 1988. Reexamination of simultaneous and backward conditioning: Implications
      for contiguity theory. Learn. Motiv. 19, 317-344].

PMID- 17194550
TI  - Susceptibility of bacteria isolated from pigs to tiamulin and enrofloxacin
      metabolites.
AB  - Susceptibilities to metabolites of tiamulin (TIA) and enrofloxacin (ENR) were
      tested using selected bacteria with previously defined minimal inhibitory
      concentrations (MIC). The TIA metabolites tested were: N-deethyl-tiamulin (DTIA),
      2beta-hydroxy-tiamulin (2beta-HTIA) and 8alpha-hydroxy-tiamulin (8alpha-HTIA),
      and the ENR metabolites were: ciprofloxacin (CIP) and enrofloxacin N-oxide (ENR
      N). Bacteria, all of porcine origin, were selected as representatives of
      bacterial infections (Staphylococcus hyicus and Actinobacillus pleuropneumoniae),
      zoonotic bacteria (Campylobacter coli) and indicator bacteria (Escherichia coli
      and enterococci). Furthermore the effects of these compounds were tested on the
      microbial community of active sludge to test any negative effect on colony
      forming units (CFU). DTIA had a potency of 12.5-50% of the potency of TIA. 2beta
      HTIA and 8alpha-HTIA had potencies less than 1% of the potency of TIA. ENR-N had
      a potency of 0.75-1.5% of the potency of ENR, while CIP and ENR had similar
      potencies. Results obtained here indicate that CIP and DTIA could contribute to
      the selective pressure for upholding antimicrobial resistant bacteria in animals
      under ENR or TIA treatment. The most potent metabolites CIP and DTIA showed
      considerable potencies against activated sludge bacteria compared to the parent
      compounds. EC(50) (microg/ml) for ENR, CIP, TIA and DTIA were 0.018 [95% CI:
      0.028-0.149], 0.064 [95% CI: 0.007-0.046], 6.0 [95% CI: 3.6-9.8], and 9.7 [95%
      CI: 5.8-16.3], respectively. This indicates that the compounds can change the
      bacterial population in the sludge, and hereby alter the properties of the
      sludge.

PMID- 17194551
TI  - Protein variability among Mycoplasma hyopneumoniae isolates.
AB  - Sodium-dodecyl-sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was used to
      study the protein variability of Mycoplasma hyopneumoniae isolates. Fifty-six M.
      hyopneumoniae isolates from 6 different countries and 37 different herds were
      used. From eight herds, more than one isolate was available. All SDS-PAGE
      patterns of isolates originating from different herds were clearly divergent.
      Intra-species protein variability was quantified using the reference strain J and
      seven field strains all obtained from different herds and classified according to
      virulence. Between the field strains, a variability of 25% was found, while the
      culture-adapted strain J was clearly divergent and showed 30% variability with
      the field strains. No clustering according to virulence was obtained, but a
      protein band of about 181kDa was present in the two highly virulent isolates
      whereas this protein band was absent in the moderately and low virulent isolates.
      Protein patterns of isolates derived from different animals from the same herd,
      were identical or differed in only a few protein bands. This study clearly
      indicates that, in agreement with previous studies on genomic diversity of M.
      hyopneumoniae isolates, proteomic variability within the species is high. Our
      study did not find clear evidence that more than one M. hyopneumoniae isolate
      circulates within a herd at a specific time point. The minor differences found
      between M. hyopneumoniae isolates from the same herd might reflect the organism's
      ability to alter its proteomic expression profile under field conditions.

PMID- 17194552
TI  - Characterisation of a SAT-1 outbreak of foot-and-mouth disease in captive African
      buffalo (Syncerus caffer): clinical symptoms, genetic characterisation and
      phylogenetic comparison of outbreak isolates.
AB  - African buffalo (Syncerus caffer) play an important role in the maintenance of
      the SAT types of foot-and-mouth disease (FMD) in southern Africa. These long-term
      carriers mostly become sub-clinically infected, maintaining the disease and
      posing a threat to other susceptible wildlife and domestic species. During an
      unrelated bovine tuberculosis experiment using captive buffalo in the Kruger
      National Park (KNP), an outbreak of SAT-1 occurred and was further investigated.
      The clinical signs were recorded and all animals demonstrated significant weight
      loss and lymphopenia that lasted 100 days. In addition, the mean cell volume and
      mean cell haemoglobin values were significantly higher than before the outbreak
      started. Virus was isolated from several buffalo over a period of 167 days post
      infection and the molecular clock estimated to be 3 x 10(-5) nucleotide
      substitutions per site per day. Seven amino acid changes occurred of which four
      occurred in hypervariable regions previously described for SAT-1. The genetic
      relationship of the outbreak virus was compared to buffalo viruses previously
      obtained from the KNP but the phylogeny was largely unresolved, therefore the
      relationship of this outbreak strain to others isolated from the KNP remains
      unclear.

PMID- 17194553
TI  - Zinc mediates normalization of hepatic drug metabolizing enzymes in chlorpyrifos
      induced toxicity.
AB  - The present study investigated the protective effects of zinc in attenuating the
      altered activities of drug metabolizing enzymes in the livers of rats intoxicated
      with chlorpyrifos. Male Sprague-Dawley rats received oral chlorpyrifos treatment
      (at a dose level of 13.5 mg/kg body weight in corn oil every alternate day), zinc
      supplementation alone (at a dose level of 227 mg/l in drinking water), or
      combined chlorpyrifos plus zinc treatments for a total duration of 8 weeks. The
      effects of different treatments were studied on the specific activities of
      various drug metabolizing enzymes including cytochrome P(450), cytochrome b(5),
      NADPH cytochrome-c-reductase, NADH cytochrome-c-reductase, aminopyrene-N
      demethylase (APD) and aromatic hydrocarbon hydroxylase (AHH). Additionally, serum
      zinc levels were also determined in each of the treatment groups at the end of
      the study. Chlorpyrifos treatment resulted in a significant decrease in the serum
      zinc concentrations. Analogous to these changes, we observed significant
      depression in the activities of majority of the drug metabolizing enzymes
      investigated in the present study, except for AHH, where the decrease in enzyme
      activity was not statistically significant. However, zinc treatment to
      chlorpyrifos treated animals effectively restored the depressed serum zinc levels
      to within normal limits. Similarly, co-administration of zinc to chlorpyrifos
      intoxicated animals normalized the enzymatic activities of cytochrome P(450),
      NADPH cytochrome-c-reductase and NADH cytochrome-c-reductase within normal range.
      Collectively, these findings suggest that zinc plays an important role in
      regulating the hepatic activities of drug metabolizing enzymes in chlorpyrifos
      intoxicated animals, although it remains to be determined whether such protective
      effects of zinc are regulated directly, or through some indirect mechanism.

PMID- 17194554
TI  - Use of hormone replacement therapy (HRT) among women aged 45-64 years in the
      German EPIC-cohorts.
AB  - OBJECTIVE: To describe the prevalence and to assess type and indicators of
      hormone replacement therapy (HRT) use in the two German EPIC-cohorts. METHODS:
      Approximately 30,000 women predominantly aged 35-65 years were recruited in EPIC
      Heidelberg and EPIC-Potsdam between 1994 and 1998. Information on diet and
      lifestyle, medical history and use of hormone therapy was collected at
      recruitment. Prevalence and type of HRT-regime was described and logistic
      regression models used to examine correlates of HRT-use. RESULTS: Among women
      aged 45-64 years, 37.9% in Heidelberg and 35.8% in Potsdam were current HRT
      users. Among current users without bilateral oophorectomy, 40.5% in Heidelberg
      and 23.7% in Potsdam used HRT for at least 5 years. Most women in Heidelberg were
      taking cyclic combined or estrogen monotherapy, whereas in Potsdam both
      continuous combined and cyclic combined therapies were most frequently used. In
      both centres, older age, ever use of oral contraceptives, and alcohol consumption
      were indicators for both current and ever HRT-use. HRT-use was less frequent in
      obese women as compared to women with lower BMI. In Potsdam, but not in
      Heidelberg, higher education and current smoking were associated with HRT-use.
      CONCLUSION: In both German EPIC-cohorts, the prevalence of medication with HRT is
      high compared to other European countries. Types of exogenous hormones used
      differed by centre. Various reproductive and lifestyle characteristics were
      identified as correlates of HRT-use.

PMID- 17194555
TI  - Sustained release of hydrophobic and hydrophilic drugs from a floating dosage
      form.
AB  - Floating dosage forms enable the sustained delivery of drugs in the gastro
      intestinal tract. In this study, a type of multi-unit floating gel bead was
      synthesized with calcium alginate, sunflower oil, and a drug of interest through
      an emulsification/gelation process. The alginate beads with oil addition were
      able to continuously float over the medium for 24h under constant agitation while
      the non-oily beads could not. Three kinds of drugs with different
      hydrophilicities, ibuprofen, niacinamide and metoclopramide HCl, were tested in
      the study. The hydrophobic drug ibuprofen was released in a sustained manner for
      24h, due to the oil partitioning. With suitable modification, the beads were able
      to also release the hydrophilic drugs, niacinamide and metoclopramide HCl, for a
      similar duration. Therefore a floating dosage form that is able to sustain
      release both hydrophobic and hydrophilic drugs within its extended gastric
      retention time has been developed.

PMID- 17194556
TI  - Effects of KIOM-79 on hyperglycemia and diabetic nephropathy in type 2 diabetic
      Goto-Kakizaki rats.
AB  - We investigated the effect of KIOM-79, 80% ethanolic extract of a new herbal
      prescription, on non-obese type 2 diabetic Goto-Kakizaki (GK) rats. The rats were
      treated orally with KIOM-79 (500 mg/kg body weight) once a day for 13 weeks to
      examine the long-term effects on hyperglycemia and glomerular histology as well
      as biochemical and functional abnormalities in kidney. As the results, we found
      that KIOM-79 reduced hyperglycemia (p<0.01), ameliorated insulin resistance
      (p<0.001), urinary protein excretion (p<0.01) and creatinine clearance (Ccr)
      (p<0.001), and inhibited glomerular AGE formation (p<0.001) in diabetic GK rats.
      We also found that KIOM-79 prevented the glomeruli enlargement, overexpression of
      type IV collagen (p<0.001), PKC protein (p<0.01), TGF-beta mRNA (p<0.05) and VEGF
      mRNA (p<0.05). Thus, based on our finding, KIOM-79 could reduce the
      hyperglycemia, and prevent or retard the development of diabetic nephropathy.

PMID- 17194557
TI  - Primary malignant melanoma of the larynx: a case report and literature review.
AB  - A 56-year-old Japanese man presented with hoarseness and left sided neck swelling
      in June 2003. Endoscopy showed an irregular tumor extending from the anterior
      commissure to the left ventricle with dark pigmentation. A biopsy showed
      malignant melanoma. A total laryngectomy with left radical neck dissection was
      performed in July 2003, followed by chemohormonal therapy and radiotherapy to the
      neck. Multiple bone metastases were diagnosed in May 2004, and the patient died
      with disseminated disease in April 2005, 21 months after initial treatment. The
      medical literature on laryngeal malignant melanoma was reviewed, and suggested a
      very poor prognosis despite therapy with surgery, radiotherapy, and chemotherapy.

PMID- 17194558
TI  - A patient with simplified gyral pattern followed by progressive brain atrophy.
AB  - We present the case of a three-year-old boy who suffered from intractable
      epilepsy from birth, and who displayed microcephaly and severe developmental
      delay. Neuroradiological examination revealed the presence of simplified gyri of
      the cerebral cortex, and increased signal intensity changes in the cerebral white
      matter on T2-weighted magnetic resonance imaging. A tentative diagnosis of
      congenital cortical malformation was made, but unexpectedly, the cerebrum,
      cerebellum, and pons showed a progressive atrophy during the follow-up period.
      The basal ganglia and thalamus were relatively spared. Investigations could find
      no evidence of leukodystrophies, metabolic disorders, hereditary brain anomalies,
      or congenital central nervous infections. This case may represent a novel type of
      neurodegenerative disease with malformation of cortical development.

PMID- 17194559
TI  - Hyperkalemia and hyperdopaminemia induced by an obsessive eating of banana in an
      anorexia nervosa adolescent.
AB  - Banana is known as a dopamine-rich and potassium-rich food, however no previous
      data regarding biochemical or psychological alteration induced by excess intake
      of banana has been reported. We have experienced an adolescent female case of
      Anorexia nervosa (AN) who denied eating anything but maximum 20 bananas and less
      than 500 ml mineral water per day for more than two years. During the period of
      massive banana eating habit, she showed increase of serum potassium (from 4.7
      mEq/l to 6.1 mEq/l) and whole blood dopamine (from 11 ng/ml to 210 ng/ml; normal
      range 0.5-6.2 ng/ml), and obvious dysthymia that is inexplicable only by the
      pathology of AN. When the patient resumed other food ingestion after 26 months of
      obsessive and restricted eating of banana, the abnormalities in her blood data
      and her psychological state were all corrected toward normal. We conclude that in
      this case, the obsessive and restricted habit of banana ingestion resulted in
      hyperkalemia, hyperdopaminemia, and psychological change.

PMID- 17194560
TI  - Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in
      rats: CT-pathologic correlation.
AB  - OBJECTIVES: To investigate the acute and repeated pulmonary damage in Sprague
      Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF)
      using computed tomography (CT), and to correlate these results with those
      obtained from a pathological study. METHODS: Sixty, 7-week-old rats were exposed
      to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N=20), 3 days (N=20), and 28
      days (5 days/week) (N=20) using whole body exposure chambers at a concentration
      of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and
      histopathologic studies were carried out. For the follow-up study, the rats
      exposed for 3 days were scanned using CT and their pathology was examined at 7,
      14, and 28 days. RESULTS: There was a significant decrease in the parenchymal
      density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p=0.022)
      or 6 ppm (p=0.010), compared with the control. The parenchymal density of the
      rats exposed to 12 ppm was significantly higher. The pathological findings in
      this period, the grades of vascular congestion, tracheobronchial exfoliation, and
      alveolar rupture were significant. In the groups exposed for 3 days, there was a
      large decrease in the parenchymal density with increasing dose (control: 
      675.48+/-32.82 HU, 3 ppm: -720.65+/-34.21 HU, 6 ppm: -756.41+/-41.68 HU, 12 ppm: 
      812.56+/-53.48 HU) (p=0.000). There were significant density differences between
      each dose in the groups exposed for 28 days (p=0.000). The CT findings include an
      irregular lung surface, areas of multifocal, wedge-shaped increased density, a
      heterogeneous lung density, bronchial dilatation, and axial peribronchovascular
      bundle thickening. The histopathology examination revealed the development of
      alveolar interstitial thickening and vasculitis, and an aggravation of the
      mainstem bronchial exudates and bronchial inflammation. The alveolar wall
      ruptures and bronchial dilatation became severe during this period. On the follow
      up study, the groups exposed for 3 days showed diffusely increased parenchymal
      density on the 7 days study, but the lung densities were lower at 14 and 28 days
      than at 3 days. In the rats exposed to lowest concentration, the pulmonary
      parenchymal density and pathologic findings rapidly returned to normal within 1
      week. CONCLUSIONS: Decreased parenchymal density of the lung was a common CT
      finding in acute and repeated inhalation injury. The air accumulation is believed
      to be the results of tracheolaryngeal inflammatory edema, bronchial dilatation,
      and alveolar rupture from the early period.

PMID- 17194561
TI  - The value of contrast enhanced ultrasonography in detection of liver metastases
      from colorectal cancer: a prospective double-blinded study.
AB  - OBJECTIVE: To compare sensitivity and specificity of contrast enhanced
      ultrasonography (CEUS) with conventional ultrasonography (US) in detection of
      liver metastases in patients with colorectal adenocarcinoma (CRC) in a patient-by
      patient analysis. MATERIALS AND METHODS: A prospective study of 461 consecutive
      patients referred to the Department of Colorectal Surgery, Aarhus University
      Hospital with primary or local recurrence of CRC. In order to detect possible
      liver metastases all patients underwent liver US, followed by CEUS by another
      investigator. Multislice CT scanning (MDCT), and intraoperative ultrasonography
      (IOUS) were then performed. Fine-needle biopsy was performed on all suspicious
      lesions. Each examination was interpreted blindly and the combination of biphasic
      MDCT, IOUS, follow up and biopsy was the gold standard. RESULTS: Standard of
      reference found liver metastases in 54 patients (14.8%). Contrast enhanced
      ultrasonography improved the sensitivity significantly in detection of liver
      metastases from 0.69 by US to 0.80 (p=0.031). In 24 patients, CEUS found a higher
      number of metastases than US (p<0.001). The specificity (0.98) and the positive
      predictive value (0.86) was the same. CONCLUSION: Contrast enhanced
      ultrasonography improves sensitivity in detection of liver metastases in patients
      with CRC and in nearly half of the cases CEUS found a higher number of metastases
      than US.

PMID- 17194562
TI  - Insulin-like growth factor-1 receptor immunoreactive cells are selectively
      maintained in the paraventricular hypothalamus of calorically restricted mice.
AB  - The mammalian lifespan is dramatically extended by both caloric restriction (CR)
      and insulin-like growth factor-1 (IGF-1) suppression. Both interventions involve
      neuroendocrine alterations directed by the hypothalamus. Yet, it remains unclear
      whether CR exerts its affects by altering central IGF-1 sensitivity. With this
      question in mind, we investigated the influence of CR and normal aging on
      hypothalamic IGF-1 sensitivity, by measuring the changes in IGF-1 receptor (IGF
      1R) populations. Taking IGF-1 receptor (IGF-1R) immunoreactivity as an index of
      sensitivity to IGF-1, we counted IGF-1R immunoreactive and non-immunoreactive
      cells in the paraventricular nucleus (PVN) of Young-ad libitum fed (Young-Al, 6
      weeks old), Old-ad libitum fed (Old-Al, 22 months old), and old calorically
      restricted (Old-CR, 22 months old) female B6D2F1 mice. An automated imaging
      microscopy system (AIMS) was used to generate cell counts for each cross-section
      of PVN hypothalamus. Ad libitum fed mice show a 37% reduction in IGF-1R
      immunoreactive cells and a 12% reduction in the total cell population of the PVN
      with aging. In comparison, caloric-restricted mice show a 33% reduction in IGF-1R
      immunoreactive cells and a notable 24% decrease in the total cell population with
      aging. This selective maintenance of IGF-1R expressing cells coupled with the
      simultaneous loss of non-immunoreactive cells, results in a higher percentage of
      IGF-1R immunoreactive cells in the PVNs of CR mice. Thus, the decline in the
      percentage of IGF-1 sensitive cells in the PVN with age is attenuated by CR.

PMID- 17194563
TI  - A motion to exclude and the 'fixed' versus 'flexible' battery in 'forensic'
      neuropsychology: challenges to the practice of clinical neuropsychology.
AB  - Two recent publications in Archives of Clinical Neuropsychology (ACN) have been
      used by defense attorneys as the centerpiece for an argument that only a 'fixed'
      battery approach, exemplified by the Halstead-Reitan battery (HRB), satisfies the
      Daubert criteria for admissibility; and therefore, the HRB represents the only
      method of forensic neuropsychological assessment that should be admitted into
      evidence. Since this case has important implications for the practice of clinical
      neuropsychology in the United States, this 'Motion to Exclude' and its rationale
      are presented, which demonstrates how the legal profession uses
      neuropsychological literature. The critical issues of this argument for clinical
      neuropsychological practice are reviewed.

PMID- 17194564
TI  - Lymphocyte expression of CD95 at rest and in response to acute exercise in
      healthy children and adolescents.
AB  - CD95 is essential in regulating the immune system, and its reduced expression has
      been associated with anthracycline resistance in some childhood leukemias. We
      determined whether an acute bout of exercise would influence the mixed lymphocyte
      expression of CD95 in healthy children and adolescents. Fifty healthy pediatric
      subjects (female n=25) cycled for 60 min @ 70% V O(2max). Blood was collected
      before, during, and after exercise to determine CD95 expression on T (CD3(+)CD19(
      )) and B (CD3(-)CD19(+)) cells using flow cytometry. At rest, the percentage of
      CD95(hi) T cells was 29% higher in girls versus boys (p<0.001). The percentage of
      CD95(hi) T cells and the median fluorescence intensity (MFI) of CD95(hi) were
      higher during recovery versus rest (p<0.0001). The percentage of CD95(lo) T cells
      was lower during recovery versus rest, whereas the MFI of CD95(lo) was higher
      during exercise versus rest. The CD95(hi) T cell count increased during exercise,
      but only in 14-yr-old girls, whereas CD95(lo) T cell counts increased similarly
      in all groups. CD95(+) B cells were relatively unresponsive to exercise. We
      conclude that lymphocyte expression of CD95 is influenced by acute exercise in
      healthy children and adolescents. Exercise-induced alterations in CD95 expression
      may have clinical implications for some pediatric conditions.

PMID- 17194567
TI  - Developmental toxicity evaluation of triclopyr butoxyethyl ester and triclopyr
      triethylamine salt in the CD rat.
AB  - Triclopyr (3,5,6-trichloro-2-pyridyloxyacetic acid) is an herbicide used
      extensively in the control of woody plants and broadleaf weeds, and is often
      formulated as a triethylamine salt (T-TEA) or butoxyethyl ester (T-BEE). This
      study evaluated the developmental toxicity of T-TEA or T-BEE in time-mated CD
      rats gavaged on gestation days 6-15 with 0, 30, 100 or 300 mg/kg body
      weight(bw)/day. The doses of each compound were equimolar and equivalent to 22,
      76, 216 mg/kg bw/day of triclopyr, based on prior studies indicating rapid
      cleavage of the salt or ester and equivalent pharmacokinetics for the active
      ingredient. T-TEA caused maternal toxicity, evidenced by the death of one high
      dose dam, reduced body weight gain, increased relative liver and kidney weights
      (300 mg/kg bw/day), reduced feed consumption, and increased water consumption
      (100 and 300 mg/kg bw/day). Developmental effects were limited to slightly
      decreased fetal body weight and reduced skeletal ossification at the high dose
      level. T-BEE caused similar, albeit slightly more severe, maternal toxicity, with
      three maternal deaths at 300 mg/kg bw/day, and slight maternal effects at 30
      mg/kg bw/day. Due to an equivocal increase in malformations, which were mainly
      clustered in litters from three high dose dams with marked maternal toxicity, the
      T-BEE study was repeated using 30 dams/group, investigator-blind fetal
      evaluations, and an additional dose group (5 mg/kg bw/day). In the repeat study,
      the only reproducible fetal effect was an increased incidence of 14th
      thoracolumbar rib at 300 mg/kg bw/day. Overall analysis of the two T-BEE studies
      suggested that the fetal malformations unique to the initial study likely
      reflected a combination of spontaneous events, exacerbated by marked maternal
      toxicity. The combined weight of evidence from these developmental toxicity
      studies, coupled with their known pharmacokinetic equivalence, indicates that T
      BEE and T-TEA are not selectively toxic to the fetus. The respective maternal
      toxicity no-observed effect levels (NOEL) for T-BEE and T-TEA were 5 and 30 mg/kg
      bw/day, while the NOEL for developmental toxicity was 100 mg/kg bw/day for both
      compounds.

PMID- 17194566
TI  - Antigen-induced inflammatory mechanical hypernociception in mice is mediated by
      IL-18.
AB  - There is pre-clinical evidence that therapies targeting IL-18 might be beneficial
      in controlling arthropathies, which are accompanied by hypernociception
      (nociceptor sensitization). In the present study, we addressed the
      hypernociceptive role of IL-18 in a model of antigen-induced inflammation in mice
      and its mechanisms. In naive mice, the intraplantar injection of IL-18 induced
      dose- and time-dependent mechanical hypernociception, which was inhibited in IFN
      gamma deficient (-/-) mice, and by the pre-treatment with bosentan (dual
      endothelin [ET] receptor antagonist), BQ123 (ET(A) receptor antagonist) or
      indomethacin (cyclooxygenase inhibitor). IL-18 hypernociception was unaffected in
      TNFR1(-/-) mice or by the pre-treatment with sIL-15Ralpha (soluble form of IL-15
      receptor), BQ788 (ET(B) receptor antagonist) or guanethidine (sympathetic
      blocker). The ovalbumin (OVA) challenge-induced mechanical hypernociception in
      immunized mice was inhibited by the pre-treatment with anti-IL-18 antibody or in
      IL-18(-/-) mice. Furthermore, IL-18 induced significant IFN-gamma production in
      the paw skin of naive mice. The OVA challenge-induced IFN-gamma and ET-1
      productions were inhibited in IL-18(-/-) immunized mice, as well as ET-1
      production in IFN-gamma(-/-) immunized mice. In addition, significant PGE2
      production was detected after IL-18 or ET-1 (via ET(A) receptors) injection in
      naive mice. Taken together with previous data, these results suggest that IL-18
      plays a significant role in antigen-induced inflammatory hypernociception via the
      production of IFN-gamma, ET-1 and PGE2. Thus, IL-18 and IL-18-downstream
      mediators demonstrated herein might constitute targets to inhibit antigen-induced
      inflammatory pain.

PMID- 17194565
TI  - An inflammatory review of glucocorticoid actions in the CNS.
AB  - In recent years, the classic view that glucocorticoids, the adrenal steroids
      secreted during stress, are universally anti-inflammatory has been challenged at
      a variety of levels. It was first observed that under some circumstances, acute
      GC exposure could have pro-inflammatory effects on the peripheral immune
      response. More recently, chronic exposure to GCs has been found to have pro
      inflammatory effects on the specialized immune response to injury in the central
      nervous system. Here we review the evidence that in some cases, glucocorticoids
      can increase pro-inflammatory cell migration, cytokine production, and even
      transcription factor activity in the brain. We consider how these unexpected
      effects of glucocorticoids can co-exist with their well-established anti
      inflammatory properties, as well as the considerable clinical implications of
      these findings.

PMID- 17194568
TI  - Preferential neuron loss in the rat piriform cortex following pilocarpine-induced
      status epilepticus.
AB  - Structures within the piriform cortex (PC) including the endopiriform nucleus
      (DEN) and pre-endopiriform nucleus (pEn) have been implicated to be involved in
      seizure genesis in models of temporal lobe epilepsy. We used stereological
      methods to examine the specificity and extent of neuron loss in the PC of
      pilocarpine-treated rats. Both 7 days and 2 months post-status epilepticus rats
      showed significant neuron loss in the pEn and DEN, layer III of the intermediate
      PC, and layers II and III of the caudal PC. Total losses in the PC were 40 and
      46% in 7 days and 2 months post-status epilepticus rats, respectively (p<0.01).
      The numbers of parvalbumin (PV)- and cholecystokinin (CCK)-immunopositive neuron
      profiles significantly decreased, and somatostatin (SS)-immunopositive neuron
      profiles tended to decrease. A large decrease in the number of PV-immunopositive
      neuron profiles occurred in the pEn, adjoining parts of the DEN and deep layer
      III of the PC, portions of the DEN bordering the claustrum and agranular insular
      cortex, and layer III of the caudal PC. The regions with decreased numbers of PV
      , CCK-, and SS-immunopositive neuron profiles overlapped with those where many
      Nissl-stained neurons were lost and many degenerating cell bodies were detected.
      These results suggest that the decreases in the numbers of PV/SS/CCK
      immunopositive neurons are related to neuron loss rather than to a low rate of
      synthesis of their peptides or proteins.

PMID- 17194569
TI  - Striate palmoplantar keratoderma resulting from a frameshift mutation in the
      desmoglein 1 gene.
AB  - BACKGROUND: Striate keratodermas (PPKS) are a group of rare autosomal dominant
      palmoplantar keratodermas, characterized by a thickening of the skin on the palms
      and soles. PPKS is characterized by hyperkeratosis extending along the length of
      each finger and on the palm of the hand, as well as by patches of hyperkeratosis
      on the soles. OBJECTIVE: We report a four-generation Pakistani kindred in which
      11 members were affected with PPKS. METHODS: Based on previous reports of DSG1
      mutations in PPKS, we performed direct DNA sequencing analysis. RESULTS:
      Clinically, these patients presented with hyperkeratotic palms and with linear
      hyperkeratosis on the fingers. Additionally, focal hyperkeratosis was seen on the
      sole of the toes as well as the ball and heel of the foot. DNA sequencing
      analysis revealed a heterozygous G-to-T transversion in the 3' splice acceptor
      site of intron 11 of the DSG1 gene designated 1688 -1 G>T. We predict that this
      mutation will lead to the skipping of exon 12 which is out of frame (134nt),
      subsequent degradation of the mutant mRNA by non-sense mediated RNA decay, and
      haploinsufficiency for DSG1. CONCLUSION: We report a novel splice site mutation
      in the DSG1 gene in PPKS, which further underscores the significance of the
      desmoglein gene family in diseases of epidermal integrity.

PMID- 17194570
TI  - Pharmacokinetic/pharmacodynamic modeling of in vitro activity of azithromycin
      against four different bacterial strains.
AB  - The bacterial time-kill curves of azithromycin against four bacterial strains
      (Streptococcus pneumoniae/penicillin-intermediate, S. pneumoniae/penicillin
      sensitive, Haemophilus influenzae and Moraxella catarrhalis) were determined by
      in vitro infection models. Eighteen different pharmacokinetic/pharmacodynamic
      models were fitted to the time-kill data using non-linear regression and compared
      for best fit. A simple, widely used E(max) model was not sufficient to describe
      the pharmacodynamic effects for the four bacterial strains. Appropriate models
      that gave good curve fits included additional terms for saturation of the number
      of bacteria (N(max)), delay in the initial bacterial growth phase and/or the
      onset of anti-infective activity (1-exp(-zt)) as well as a Hill factor (h) that
      captures the steepness of the concentration-response profile. Azithromycin was
      highly effective against S. pneumoniae strains and M. catarrhalis while the
      efficacy against H. influenzae was poor. Applications of these
      pharmacokinetic/pharmacodynamic models will eventually provide a tool for
      rational antibiotic dosing regimen decisions.

PMID- 17194571
TI  - Relative efficacy of psychotherapy and combined therapy in the treatment of
      depression: a meta-analysis.
AB  - BACKGROUND: Reviews of the relative efficacy of psychotherapy and combined
      therapy (psychotherapy with pharmacotherapy) for depression have yielded
      contradicting conclusions. This may be explained by the clinical heterogeneity of
      the studies reviewed. AIMS: To conduct a meta-analysis with an acceptable level
      of homogeneity in order to investigate the relative efficacy of psychotherapy and
      combined therapy in the acute treatment of depression. METHOD: A systematic
      search was performed for RCTs published between 1980 and 2005 comparing
      psychotherapy and combined therapy in adult psychiatric outpatients with non
      psychotic unipolar major depressive disorder. The studies were classified
      according to the chronicity and severity of the depression. Data were pooled by
      means of meta-analysis and statistical tests were conducted to measure
      heterogeneity. RESULTS: The meta-analysis included seven studies looking at a
      total of 903 patients. None of the heterogeneity tests established significance.
      This indicates a lack of evidence for the heterogeneity of the results. The
      dropout rates did not differ significantly between the two treatment modalities
      (25% in combined therapy and 24% in psychotherapy, p=0.77). At treatment
      termination, the intention-to-treat remission rate for combined therapy (46%) was
      better than for psychotherapy (34%) (p=0.0007); Relative Risk 1.32 (95% CI: 1.12
      1.56), Odds Ratio 1.59 (95% CI: 1.22-2.09). In moderate depression, the
      difference between the remission rate for combined therapy and psychotherapy was
      statistically significant (47% compared to 34% respectively, p=0.001). This was
      not the case in mild major depression (42% compared to 37% respectively, p=0.29).
      The difference was also statistically significant in chronic major depression
      (48% compared to 32%, p<0.001), but not in non-chronic major depression (43%
      compared to 37%, p=0.22). On a more specific level, no differences were found in
      the remission rates for the treatment modalities in mild or moderate non-chronic
      depression. Combined therapy led to significantly better results than
      psychotherapy in moderate chronic depression only (48% compared to 32%, p<0.001).
      CONCLUSIONS: In the acute treatment of adult psychiatric outpatients with major
      depressive disorder, patient compliance with combined therapy matches compliance
      with psychotherapy alone. Combined therapy is more efficacious than psychotherapy
      alone. However, these results depend on severity and chronicity. Combined therapy
      outperformed psychotherapy in moderate chronic depression only. No differences
      were found in mild and moderate non-chronic depression. No data were found for
      mild chronic depression and for severe depression.

PMID- 17194572
TI  - Problem solving therapies for depression: a meta-analysis.
AB  - PURPOSE: In the past decades, the effects of problem-solving therapy (PST) for
      depression have been examined in several randomized controlled studies. However,
      until now no meta-analysis has tried to integrate the results of these studies.
      METHODS: We conducted a systematic literature search and identified 13 randomized
      studies examining the effects of PST, with a total of 1133 subjects. The quality
      of studies varied. RESULTS: The mean standardized effect size was 0.34 in the
      fixed effects model and 0.83 in the random effects model, with very high
      heterogeneity. Subgroup analyses indicated significantly lower effects for
      individual interventions in studies with subjects who met criteria for major
      depression, studies in which intention-to-treat analyses were conducted instead
      of completers-only analyses, and studies with pill placebo and care-as-usual
      control groups. Heterogeneity was high, and the subgroup analyses did not result
      in clear indications of what caused this high heterogeneity. This indicates that
      PST has varying effects on depression, and that it is not known to date what
      determines whether PST has larger of smaller effects. CONCLUSION: Although there
      is no doubt that PST can be an effective treatment for depression, more research
      is needed to ascertain the conditions and subjects in which these positive
      effects are realized.

PMID- 17194574
TI  - Zeolite inorganic supports for BSA immobilization: comparative study of several
      zeolite crystals and composite membranes.
AB  - Zeolites due to their low toxicity and high compatibility are considered new
      biomaterials for medical applications. The surface adsorption behaviour of
      zeolite crystals and composite membranes was discussed in this research. The
      zeolite materials were synthesized by hydrothermal syntheses using different
      reaction gels to modulate the Bronsted acidity of the microporous structures.
      Spectrophotometric analyses were used to evaluate protein adsorption on these
      surfaces. This study revealed that zeolite chemical composition and structure
      influenced the kinetics of protein adsorption. Zeolite Y surface adsorbed greater
      amount of BSA than the other structures. The percentage of adsorption increases
      with temperature and depends on the pH of the solution, being highest at the pI
      of the protein. The influence of the membrane configuration on the protein
      adsorption was studied using different zeolite structures and crystallization
      types. It seems that the observed differences could depend on the type of
      hydrothermal crystallization inside the inorganic support.

PMID- 17194573
TI  - The economic burden of depression in Sweden from 1997 to 2005.
AB  - BACKGROUND: Depression is one of the most common causes of disability and is
      associated with substantial reductions in the individual's quality of life. The
      aim of this study was to estimate the economic burden of depression to Swedish
      society from 1997 to 2005. MATERIALS AND METHODS: The study was conducted in a
      cost-of-illness framework, measuring both the direct cost of providing health
      care to depressive patients, and the indirect costs as the value of production
      that is lost due to morbidity or mortality. The costs were estimated by a
      prevalence and top-down approach. RESULTS: The cost of depression increased from
      a total of 1.7 billion euros in 1997 to 3.5 billion euros in 2005, representing a
      doubling of the burden of depression to society. The main reason for the cost
      increase is found in the significant increase in indirect costs due to sick leave
      and early retirement during the past decade, whereas direct costs were relatively
      stable over time. In 2005, indirect costs were estimated at 3 billion euros (86%
      of total costs) and direct costs at 500 million euros (16%). Cost of drugs was
      estimated at 100 million euros (3% of total cost). CONCLUSION: The cost of
      depression is substantial to society and the main cost driver is indirect costs
      due to sick leave and early retirement. The cost of depression has doubled during
      the past eight years making it a major public health concern for the individuals
      afflicted, carers and decision makers.

PMID- 17194575
TI  - An optimized assay for transcription factor NF-kappaB with dsDNA-coupled
      microplate.
AB  - To develop an EMSA-free assay approach for analyzing the sequence-specific DNA
      binding proteins (DBPs), an easy cost-effective dsDNA-coupled plate (dcPlate) was
      developed in our lab for this purpose. In this paper, the assay conditions of
      such dcPlate were fully optimized for detecting an important transcription
      factor, NF-kappaB. The optimized parameters of dcPlate for assay of NF-kappaB
      were as follows: immobilized DNA probe at the concentration of 25 pmol/100 microL
      well, incubation time of 90 min for NF-kappaB binding to dcPlate, primary and
      secondary antibody concentration of 0.1 microL/100 microL dilution, incubation
      time of 90 min for primary antibody binding to NF-kappaB, temperature of 25
      degrees C for the above process, colorimetric developing time for 30 min. After
      optimization, the signal was improved three times higher than that from not
      optimized conditions. The linear colorimetric detection ranges of the purified
      recombinant NF-kappaB p50 and the cell nuclear extract were from 0.59 to 75
      ng/well and 0.313 to 10 microg/well, respectively.

PMID- 17194576
TI  - Effect of roughness on particle adhesion in aqueous solutions: a study of
      Saccharomyces cerevisiae and a silica particle.
AB  - An atomic force microscope (AFM) has been used to quantify the adhesion of living
      cells Saccharomyces cerevisiae on three different silica surfaces with defined
      roughness. The effects of support roughness on the adhesion forces of a smooth
      silica particle were studied in addition. A living single cell was immobilized at
      the apex of a tipless AFM cantilever using a key-lock mechanism. Adhesion was
      quantified from the force-distance data measured on a smooth silica substrate and
      two substrates coated with hydrophilic monodisperse silica particles with 110 and
      240 nm in diameter to study the effect of roughness on particle adhesion. The AFM
      technique gives unique insight into the primary colonization event of biofilm
      formation. The new knowledge helps substantially to design surface coatings
      relevant for biotechnology, medicine and dentistry.

PMID- 17194577
TI  - Effect of core-shell micelle formation on the redox properties of phenothiazine
      labeled poly(ethyl glycidy ether)-block-poly(ethylene oxide).
AB  - Redox properties of phenothiazine-labeled poly(ethyl glycidy ether)-block
      poly(ethylene oxide) (PT-EGE(n)-b-EO(m)) are reversibly changed by core-shell
      micelle formation. In the temperature range higher than the critical
      micellization temperature (cmt), the anodic potential of PT group positively
      shifts and concomitantly its anodic current decrease, or levels off compared to
      those of the reference polymer PT-EO(m) without the thermo-responsive EGE(n)
      segment. The former alteration is caused by incorporation of hydrophobic PT
      groups into a core of the micelle and the latter by the decrease in the diffusion
      coefficient of PT groups due to formation of the core-shell micelles. The cmt
      value and the temperature-dependent alteration in the redox properties strongly
      depend on the polymer structure, especially the length of thermo-responsive
      EGE(n) segment. The electrochemically determined hydrodynamic radii of the
      polymer aggregates seem to be overestimated, compared to the values reported for
      the aggregates of other thermo-responsive polymers with similar molecular
      weights, implying the presence of electrochemically inactive PT groups in the
      copolymers having longer thermo-responsive segments.

PMID- 17194579
TI  - Mechanistic modeling of digoxin distribution kinetics incorporating slow tissue
      binding.
AB  - This study aims to develop a mechanistic pharmacokinetic model that accounts for
      the kinetics of tissue binding in order to evaluate the effect of slow binding of
      digoxin to skeletal muscular Na(+)/K(+)-ATPase in humans. The approach is based
      on a minimal circulatory model with a systemic transit time density function that
      accounts for vascular mixing, transcapillary permeation and extravascular binding
      of the drug. The model parameters were estimated using previously published
      disposition data of digoxin in healthy volunteers and physiological distribution
      volumes taken from the literature. A time constant of the binding process of
      34min was estimated indicating that receptor binding and not permeation clearance
      is the rate-limiting step of the distribution process. Model simulations suggest
      that up- or downregulation of sodium pumps, typically observed under
      physiological or pathophysiological conditions, could be detected with this
      method. The model allows a quantitative prediction of the effect of changes in
      skeletal muscular sodium pump activity on plasma levels of digoxin.

PMID- 17194580
TI  - Tensile stresses generated in pharmaceutical tablets by opposing compressive line
      loads.
AB  - The distribution of tensile stress, across the splitting plane, has been
      investigated for the case when circular and square tablets are subjected to
      opposing compressive line loads acting in the through thickness direction. This
      type of loading is referred to in the paper as axial compression. Analytical
      solutions for the two-dimensional problem of a rectangular strip have been used
      to investigate the variation of stress in the through thickness direction and to
      consider the effects of load spreading. Three-dimensional finite element analysis
      has been used to investigate the variation in stress across the diameter, or
      breadth, of the tablets. It is shown that the magnitude of the tensile stress
      varies significantly throughout and that load spreading has an important
      influence on the stress distribution in the through thickness direction.
      Experiments have been carried out with microcrystalline cellulose (Avicel PH102)
      material for circular and square tablets to determine their breaking loads when
      subjected to axial compression and diametral compression. The experimental
      results show higher breaking loads for the case of axial compression. It is
      concluded that the platen contact width must be known in order to evaluate the
      exact value of the tensile strength of the tablet material when applying this
      test procedure.

PMID- 17194581
TI  - Shaping the actin cytoskeleton using microtubule tips.
AB  - The microtubule cytoskeleton serves as a primary spatial regulator of cell shape.
      As part of their function, microtubules appear to activate or inhibit the actin
      cytoskeleton at specific locations at the cell cortex for cell polarization, cell
      migration and cytokinesis. Recent studies reveal molecular insights into these
      processes. Regulators of the actin cytoskeleton, such as activators of formin and
      Rho GTPases, are transported to specific sites on the cortex by riding on the
      plus ends of microtubules.

PMID- 17194582
TI  - Ribonuclease revisited: structural insights into ribonuclease III family enzymes.
AB  - Ribonuclease III (RNase III) enzymes occur ubiquitously in biology and are
      responsible for processing RNA precursors into functional RNAs that participate
      in protein synthesis, RNA interference and a range of other cellular activities.
      Members of the RNase III enzyme family, including Escherichia coli RNase III,
      Rnt1, Dicer and Drosha, share the ability to recognize and cleave double-stranded
      RNA (dsRNA), typically at specific positions or sequences. Recent biochemical and
      structural data have shed new light on how RNase III enzymes catalyze dsRNA
      hydrolysis and how substrate specificity is achieved. A major theme emerging from
      these studies is that accessory domains present in different RNase III enzymes
      are the key determinants of substrate selectivity, which in turn dictates the
      specialized biological function of each type of RNase III protein.

PMID- 17194583
TI  - Regulation of human estrogen receptor alpha-mediated gene transactivation in
      Saccharomyces cerevisiae by human coactivator and corepressor proteins.
AB  - Human estrogen receptor alpha (ERalpha)-mediated transcription activation was
      evaluated in the yeast Saccharomyces cerevisiae using both the native ERalpha and
      a G400V variant. A previous study demonstrated that coexpression of human SRC-1,
      a potent stimulator of ERalpha function in mammalian cells, potentiated ERalpha
      mediated gene expression in yeast over five-fold in an E(2)-dependent manner. In
      the present study, two additional human coactivator proteins were shown to
      potentiate ERalpha-mediated gene expression in yeast. SRC2 potentiated
      transactivation two- to three-fold while SRC3 potentiated transactivation five-
      to eight-fold. Both human coactivators potentiated both the native ERalpha and
      the G400V variant in an E(2)-dependent manner. The effect of a human corepressor
      protein was also evaluated in yeast. Repressor of estrogen receptor activity
      (REA) did not affect E(2)-induced transactivation by ERalpha (either isoform).
      However, in a strain that coexpressed human SRC1, REA reduced E(2)-induced
      transactivation to that observed with ERalpha alone. Furthermore, repression of
      SRC1 potentiation was specific for the native ERalpha since REA had no effect on
      SRC1 potentiation of the G400V variant. Additionally, REA repression was specific
      for SRC1 since potentiation of ERalpha (either isoform) transactivation by SRC2
      and SRC3 was unaffected by coexpression of REA. These results support previous
      observations in mammalian cells that REA does not prevent ERalpha from binding to
      DNA but does inhibit potentiation of ERalpha-mediated transactivation by SRC1.
      The results in the present study further characterize REA-mediated repression,
      and demonstrate the utility of this yeast system for dissecting molecular
      mechanisms involved in regulating gene transactivation by human ERalpha.

PMID- 17194584
TI  - A potent and orally active HIV-1 integrase inhibitor.
AB  - A 1,6-naphthyridine inhibitor of HIV-1 integrase has been discovered with
      excellent inhibitory activity in cells, good pharmacokinetics, and an excellent
      ability to inhibit virus with mutant enzyme.

PMID- 17194586
TI  - Synthesis of new xanthone analogues and their biological activity test-
      cytotoxicity, topoisomerase II inhibition, and DNA cross-linking study.
AB  - In this report, we prepared some 3-(2',3'-epoxypropoxy)xanthones and their
      epoxide ring opened halohydrin analogues, and evaluated their cytotoxicity and
      topoisomerase II inhibition activity using doxorubicin and etoposide as
      references, respectively. Another xanthone compound 9, 1,3-di(2',3'
      epoxypropoxy)xanthone, was also synthesized and its DNA cross-linking property
      including other two biological activities investigated. The biological test
      results showed compound 9 possessed excellent cytotoxic and topoisomerase II
      inhibitory activity than other compounds tested. It also exhibited significant
      DNA cross-linking activities.

PMID- 17194585
TI  - Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase
      inhibitor by high-throughput screening.
AB  - A high-throughput screening campaign of a library of 100,000 lead-like compounds
      identified 2-iminobenzimidazoles as a novel class of trypanothione reductase
      inhibitors. These 2-iminobenzimidazoles display potent trypanocidal activity
      against Trypanosoma brucei rhodesiense, do not inhibit closely related human
      glutathione reductase and have low cytotoxicity against mammalian cells.

PMID- 17194588
TI  - N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective,
      inhibitors of JNK2 and JNK3.
AB  - The identification and exploration of a novel, potent and selective series of N
      (3-cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amide inhibitors of JNK2 and JNK3
      kinases is described. Compounds 5a and 11a were identified as potent inhibitors
      of JNK3 (pIC50 6.7 and 6.6, respectively), with essentially equal potency against
      JNK2 (pIC50 6.5). Selectivity within the mitogen-activated protein kinase (MAPK)
      family, against JNK1, p38alpha and ERK2, was observed for the series. X-ray
      crystallography of 5e and 8a in JNK3 revealed a unique binding mode, with the 3
      cyano substituent forming an H-bond acceptor interaction with the hinge region of
      the ATP-binding site.

PMID- 17194587
TI  - 3-[2-((2S)-2-cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramide
      analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes.
AB  - Based on the structures of NVP-DPP728 (1) and NVP-LAF237 (Vildagliptin, 2), three
      series of DPP-IV inhibitors were synthesized by linking substituted anilines,
      benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine through a linker.
      More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and
      selectivity profile over DPP-II, DPP8, and FAP enzymes. Selected compounds 5f and
      7i showed in vivo plasma DPP-IV inhibition and inhibited glucose excursion in
      OGTT after oral administration in Wistar rats. Compound 5f (DPP-IV IC50 = 116 nM)
      has the potential for development as antidiabetic agent.

PMID- 17194589
TI  - 'Open minded' cells: how cells can change fate.
AB  - It has long intrigued researchers why some but not all organisms can regenerate
      missing body parts. Plants are remarkable in that they can regenerate the entire
      organism from a small piece of tissue, or even a single cell. Epigenetic
      mechanisms that control chromatin organization are now known to regulate the
      cellular plasticity and reprogramming necessary for regeneration. Interestingly,
      although animals and plants have evolved different strategies and mechanisms to
      control developmental processes, they have maintained many similarities in the
      way they regulate chromatin organization. Given that plants can rapidly switch
      fate, we propose that an understanding of the mechanisms regulating this process
      in plant cells could provide a new perspective on cellular dedifferentiation in
      animals.

PMID- 17194590
TI  - Iron uptake and metabolism in the new millennium.
AB  - Iron is an essential element for metabolic processes intrinsic to life, and yet
      the properties that make iron a necessity also make it potentially deleterious.
      To avoid harm, iron homeostasis is achieved through iron transport, storage and
      regulatory proteins. The functions of some of these molecules are well described,
      for example transferrin and transferrin receptor-1, whereas the roles of others,
      such as the transferrin homolog melanotransferrin, remain unclear. The past
      decade has seen the identification of new molecules involved in iron metabolism,
      such as divalent metal transporter-1, ferroportin-1, hepcidin, hemojuvelin and
      heme carrier protein-1. Here, we focus on these intriguing new molecules and the
      insights gained from them into cellular iron uptake and the regulation of iron
      metabolism.

PMID- 17194591
TI  - Effects of changing the initial horizontal location of the center of mass on the
      anticipatory postural adjustments and task performance associated with step
      initiation.
AB  - The aim of this study was to elucidate whether and how the duration and/or
      amplitude parameters of anticipatory postural adjustments (APAs) affected the
      task performance in a single step forward from differences in the initial
      horizontal location of CoM. Ten male subjects performed initiation of a single
      step forward with the right swing leg with strict regulation of the step length
      at three initial body positions (Sw, step initiation from a 50% position of the
      center of pressure (CoP) shift in the maximum lateral right side; N, step
      initiation from the upright position at rest; St, step initiation from a 50%
      position of the CoP shift in the maximum lateral left side). The duration
      required for stepping from the heel-off to foot-contact of the swing leg (step
      time) in the Sw condition was significantly shorter than of the other two
      conditions. The APAs durations in the Sw condition was significantly longer than
      in the other two conditions. In the Sw condition, the durations of the
      anticipatory electromyographic (EMG) activities of the tibialis anteriors (TA) of
      the swing leg correlated significantly with mechanical parameters (the
      displacement of the CoM, velocity of the CoM, and propulsive force) in the
      anticipatory phase, while the mean amplitudes of the anticipatory EMG activities
      of the TA of the swing leg did not correlate significantly with mechanical
      parameters in the anticipatory phase. The present results suggest that the
      duration parameters of the APAs associated with single step forward motion are
      dependent on the displacement of the CoM estimated by the initial cutaneous
      messages from the swing leg prior to initiation of the single step, and that the
      APAs may be directly involved not only in the increase in propulsive force
      towards the supporting leg, but also increasing the forward propulsive force at
      heel-off.

PMID- 17194592
TI  - Secreted bacterial phospholipase A2 enzymes: better living through
      phospholipolysis.
AB  - Phospholipases are ubiquitous and diverse enzymes that induce changes in membrane
      composition, activate the inflammatory cascade and alter cell signaling pathways.
      Recent evidence suggests that certain bacterial pathogens have acquired genes
      encoding secreted phospholipase A2 enzymes through lateral gene transfer events.
      The two best-studied members of this class of enzyme are ExoU and SlaA, which are
      produced by Pseudomonas aeruginosa and group A Streptococcus, respectively. These
      enzymes modulate the host inflammatory response, increase the severity of disease
      and otherwise alter host-pathogen interactions. We propose that a key function of
      ExoU and SlaA is to increase the fitness of the subclones expressing these
      enzymes, thereby increasing the population size of the PLA2-positive strains and
      enhancing the likelihood of encountering an at-risk host.

PMID- 17194593
TI  - The A218C polymorphism of tryptophan hydroxylase gene and migraine.
AB  - OBJECTIVE: To determine the significance of the A218C polymorphism of the
      tryptophan hydroxylase (TPH) gene in migraine. METHODS: Fifty-nine migraineurs
      and 62 healthy controls were included in the study, and polymerase chain reaction
      - restriction fragment length polymorphism assays were used to determine TPH
      A218C polymorphism. RESULTS: There was no association between TPH gene
      polymorphism and gender, family history of migraine and epilepsy, or aura. There
      was no significant difference between the allele frequencies of both groups
      (p>0.05). A significant difference was found between the genotypes of the
      migraineurs and controls regarding the AA genotype. Homozygosity for the C allele
      or heterozygosity for the A or C was not associated with the occurrence of
      migraine (p>0.05), but homozygosity for the A allele was less frequent in the
      migraineurs (p=0.02). CONCLUSION: Since it is unlikely that TPH polymorphism
      alters serotonin biosynthesis, its association with migraine may be attributed to
      linkage disequilibrium with a functional variant within the TPH gene or a nearby
      gene.

PMID- 17194594
TI  - Tremor/ataxia syndrome and fragile X premutation: diagnostic caveats.
AB  - The fragile X-associated tremor/ataxia syndrome (FXTAS) is a newly discovered
      late-onset neurodegenerative disorder caused by a premutation in the FMR1 X
      linked gene. We present examples of a discrepancy between obvious brain changes
      observed on MRI, and minimal clinical neurological manifestations in three older
      carriers of this premutation. This discrepancy occurred in three of nine carriers
      ascertained in an unbiased manner. If the systematic follow-up studies of adult
      carriers confirm this trend, this will have an impact on early diagnosis of
      neurological involvement and possible prevention. If MRI changes precede clinical
      manifestation of FXTAS this may explain the low detection rate of fragile X
      carriers among patients with neurological syndromes associated with
      tremor/ataxia.

PMID- 17194595
TI  - Synthesis and biological evaluation of benzoic acid derivatives as potent, orally
      active VLA-4 antagonists.
AB  - A series of benzoic acid derivatives was synthesized as VLA-4 antagonists.
      Introduction of chlorine or bromine into the 3-position on the central benzene of
      the diphenylurea portion as in lead compound 2 led to improvement in the
      pharmacokinetic properties. In particular, 12l demonstrated an acceptable plasma
      clearance and bioavailability in mice and rats as well as dogs (mice, CL=18.5
      ml/min/kg,F=28%; rats, CL=5.2 ml/min/kg,F=36%; dogs, CL=3.6 ml/min/kg,F=55%).
      Additionally, 12l exhibited potent activity with an IC50 value of 0.51 nM and
      efficacy by oral administration at a dosage of 10 mg/kg in a rat pleurisy model.

PMID- 17194596
TI  - Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of
      benzofuroquinolinediones.
AB  - Benzofuroquinolinediones (7c and 7d) were synthesized by base-catalyzed
      condensation of dichloroquinolinediones with phenolic derivatives. Their
      dialkylaminoalkoxy derivatives (8i-8p) were prepared by reaction with various
      dialkylaminoalkyl chlorides. The cytotoxicity of the synthesized compounds was
      evaluated against eight types of human cancer cell lines, and their topoisomerase
      II inhibition was assessed. In general, the cytotoxicity of
      benzofuroquinolinediones (8i-8p) was similar or superior to that of doxorubicin
      and showed more potent inhibitory activity than naphthofurandiones (8a-8h). Also,
      most of the compounds exhibited excellent topoisomerase II inhibitory activity at
      a concentration of 5 microM and two compounds, 8d and 8i, showed IC50 values of
      1.19 and 0.68 microM, respectively, and were much more potent than etoposide
      (IC50=78.4 microM), but similar to doxorubicin (IC50=2.67 microM). However their
      inhibitory activity on topoisomerase I was lower, and 8d and 8i showed IC50
      values of 42.0 and 64.3 microM, respectively.

PMID- 17194597
TI  - Methylcytosine-selective fluorescence quenching by osmium complexation.
AB  - We report on the control of the emission from a fluorophore fixed on DNA using
      the methylcytosine-selective addition of an osmium-bipyridine complex. We have
      synthesized DNA modified by a microenvironment-sensitive fluorophore, 2
      dimethylamino-6-acyl-naphthalene. The emission from the fluorophore tethered to a
      probe DNA was effectively quenched by a methylcytosine glycol-osmium-bipyridine
      triad, which was located in the immediate neighborhood of the fluorophore. The
      discrimination of the cytosine methylation status at a methylation hot spot in
      the p53 gene was also executed using a well-designed fluorescent DNA probe.

PMID- 17194598
TI  - 99mTc(CO)3-VIP analogues: preparation and evaluation as tumor imaging agent.
AB  - Vasoactive intestinal peptide (VIP) receptors are expressed abundantly on many
      types of tumors and, hence, radiolabeled VIP analogues are being explored for
      tumor imaging and therapy. Here, we report synthesis of three VIP analogues and
      their radiolabeling with (99m)Tc via a novel tricarbonyl synthon. The
      radiolabeled product could be prepared in high yields (>95%) and stability. In
      vitro studies showed significant uptake of (99m)Tc(CO)((3))-VP05 in human colon
      carcinoma cells. Biodistribution studies in animal tumor model showed 0.4-1%ID/g
      tumor uptake.

PMID- 17194599
TI  - Supradiaphragmatic thoracic duct clipping for chylothorax through left-sided
      video-assisted thoracoscopic surgery.
AB  - Chylothorax is a life-threatening clinical entity. Traditional surgical
      management for cases refractory to conservative treatment is thoracic duct
      ligation through a right open thoracotomy or closure of the site of duct
      laceration through an open thoracotomy. We report herein two patients with left
      chylothorax successfully treated by supradiaphragmatic thoracic duct (STD)
      ligation through left-sided video-assisted thoracoscopic surgery (VATS). This
      approach offers optimal exposure for the thoracic duct ligation and is useful for
      treatment of left chylothorax after left-sided thoracic surgery and idiopathic
      left chylothorax.

PMID- 17194600
TI  - Initial experience with the world's first digital drainage system. The benefits
      of recording air leaks with graphic representation.
AB  - OBJECTIVE: To evaluate the clinical efficacy of a new digital drainage system,
      the DigiVent Chest Drainage System that gives accurate measurements of air
      leakage and pleural pressures and can display those measurements over time.
      METHODS: The DigiVent Chest Drainage System was tested in three steps: Step 1;
      first clinical use in five patients, Step 2; management and acceptance in further
      15 patients and Step 3; reliability in routine use in 50 patients. RESULT: The
      results from Steps 1 and 2 showed that the system was good enough for extended
      use. The results from Step 3 showed excellent clinical performance, however, we
      experienced device malfunctions in four cases without any consequences for the
      patients. The cause of the malfunctions was identified and steps taken to prevent
      their further occurrence. CONCLUSION: The ability of the DigiVent to measure
      airflow and present mean values for 1, 3 and 6h proved to be very practical. The
      ability to save data and present curves for the entire course of treatment will
      be an advantage for research in the field of lung surgery.

PMID- 17194601
TI  - An analysis of the spatial arrangement of the myocardial aggregates making up the
      wall of the left ventricle.
AB  - OBJECTIVE: We used the technique of peeling of myocardial aggregates, usually
      described as 'fibres', to determine the spatial arrangement of the myocytes in
      the left ventricular wall of a healthy autopsied human heart. METHODS: We
      digitised the left ventricular outer and inner boundaries, as well as the
      pathways in space, of almost 3000 aggregates harvested from the left ventricular
      myocardium. During the process of gradual peeling, we sought to identify the
      myocardial aggregates as uniformly as possible. Despite this, interpolation was
      necessary to complete the pattern so as to construct a unit vector field that
      represented the preferred direction of the myocardial aggregates throughout the
      entirety of the walls of the left ventricle of this individual human heart.
      RESULTS: Apart from the overall systematic arrangement of the aggregates
      necessary to achieve physiologic ventricular contraction, we documented
      substantial local heterogeneities in the orientation of the myocardial
      aggregates. In particular, a significant proportion of aggregates was found to
      intrude obliquely with respect to the ventricular boundaries, with markedly
      heterogeneous distribution. Moreover, the distribution of the helical angle of
      the aggregates relative to the ventricular base varied notably throughout the
      left ventricular free walls and the septum. Within the generally quite uniform
      and continuous structure of the ventricular mass, we were, however, unable to
      identify any organised tracts or functional subunits such as a 'helical
      ventricular band', nor did we find radial fibrous lamellas coursing across the
      ventricular wall. CONCLUSION: We suggest that the impact of local anatomical
      inhomogeneities, associated with gradients in regional contractile function on
      global ventricular dynamics, has been systematically underestimated in the past.
      Our analysis confirms furthermore the continuous nature of the myocardium
      associated with an overall gross organisation of the fibre direction field;
      however, there is no evidence of substructures compartmentalising the ventricles.

PMID- 17194602
TI  - On-column refolding purification and characterization of recombinant human
      interferon-lambda1 produced in Escherichia coli.
AB  - Interferon-lambda1 (IFN-lambda1) is a member of the recently discovered type III
      IFNs (IFN-lambda), which possesses antiviral, antitumor, and immunomodulatory
      activities. In this study, the recombinant human IFN-lambda1 containing a
      hexahistidine tag was expressed in Escherichia coli. IFN-lambda1 was
      overexpressed under the control of T7 promoter and most of the protein existed in
      the form of inclusion bodies. The expressed insoluble protein was solubilized
      with urea, purified and refolded by one-step immobilized metal-ion affinity
      chromatography using Ni(2+)-nitrilotriacetic acid agarose. The purified IFN
      lambda1 appeared as a single band on SDS-PAGE and the purity was more than 95%.
      The yield was 86 mg IFN-lambda1 from 1L of bacterial culture. Western blotting
      and N-terminal sequencing confirmed the identity of the purified protein. The
      purified IFN-lambda1 exhibited specific antiviral activity as demonstrated by a
      cytopathic effect reduction assay. Thus, this on-column refolding method provides
      an efficient way to obtain an active IFN-lambda1 with high yield and high purity.

PMID- 17194603
TI  - A study of collective atomic fluctuations and cooperativity in the U1A-RNA
      complex based on molecular dynamics simulations.
AB  - Cooperative interactions play an important role in recognition and binding in
      macromolecular systems. In this study, we find that cross-correlated atomic
      fluctuations can be used to identify cooperative networks in a protein-RNA
      system. The dynamics of the RRM-containing protein U1A-stem loop 2 RNA complex
      have been calculated theoretically from a 10 ns molecular dynamics (MD)
      simulation. The simulation was analyzed by calculating the covariance matrix of
      all atomic fluctuations. These matrix elements are then presented in the form of
      a two-dimensional grid, which displays fluctuations on a per residue basis. The
      results indicate the presence of strong, selective cross-correlated fluctuations
      throughout the RRM in U1A-RNA. The atomic fluctuations correspond well with
      previous biophysical studies in which a multiplicity of cooperative networks have
      been reported and indicate that the various networks identified in separate
      individual experiments are fluctuationally correlated into a hyper-network
      encompassing most of the RRM. The calculated results also correspond well with
      independent results from a statistical covariance analysis of 330 aligned RRM
      sequences. This method has significant implications as a predictive tool
      regarding cooperativity in the protein-nucleic acid recognition process.

PMID- 17194605
TI  - Genetic variation and phylogeography of the swordtail fish Xiphophorus cortezi
      (Cyprinodontiformes, Poeciliidae).
AB  - Swordtail fish have been studied extensively in relation to diverse aspects of
      biology; however, little attention has been paid to the patterns of genetic
      variation within and among populations of swordtails. In this study, we sequenced
      the mtDNA control region from 65 individuals and 10 populations of Xiphophorus
      cortezi to investigate the genetic variation within and among populations,
      including tests for correlations between genetic and geographic distances and
      tests for species monophyly. We found low gene and nucleotide diversity within
      populations and high degrees of genetic differentiation among populations.
      Significant and positive correlations between genetic distance and both river and
      straight-line geographic distance indicate that genetic differentiation among X.
      cortezi populations can be explained, to some extent, by an isolation-by-distance
      model and provide evidence of stream capture. Phylogenetic analyses suggest that
      X. cortezi is paraphyletic relative to X. malinche, raising questions concerning
      the status of these taxa as separate species.

PMID- 17194604
TI  - The immunostimulatory effects of hot-water extract of Gelidium amansii via
      immersion, injection and dietary administrations on white shrimp Litopenaeus
      vannamei and its resistance against Vibrio alginolyticus.
AB  - The total haemocyte count (THC), phenoloxidase activity, and respiratory burst
      were examined when white shrimp Litopenaeus vannamei were immersed in seawater
      (34 per thousand) containing hot-water extract of red alga Gelidium amansii at
      200, 400 and 600 mg l(-1), injected with hot-water extract at 4 and 6 microg g(
      1) shrimp, and fed diets containing hot-water extract at 0, 0.5, 1.0 and 2.0 g
      kg(-1). These parameters increased significantly when shrimp were immersed in
      seawater containing hot-water extract at 400 and 600 mg l(-1) after 1h, when
      shrimp were injected with hot-water extract at 6 microg g(-1) shrimp after one
      day, and when shrimp were fed diets containing hot-water extract at 1.0 and 2.0 g
      kg(-1) after 14 days. Phagocytic activity and clearance efficiency were
      significantly higher for the shrimp that were fed diets containing hot-water
      extract at 1.0 and 2.0 g kg(-1) than those of shrimp that were fed diets
      containing hot-water extract at 0 and 0.5 g kg(-1) after 14 and 28 days. In a
      separate experiment, L. vannamei which had received hot-water extract via
      injection, or fed diets containing hot-water extract, were challenged after 3h or
      28 days with V. alginolyticus at 2 x 10(6) cfu shrimp(-1) and 1 x 10(6) cfu
      shrimp(-1), respectively, and then placed in seawater. The survival of shrimp
      that were injected with hot-water extract at 6 microg g(-1) was significantly
      higher than that of control shrimp after 1 day, and the survival of shrimp fed
      diets containing hot-water extract at 0.5, 1.0 and 2.0 g kg(-1) increased
      significantly after 3 days as well as at the end of the experiment (6 days after
      the challenge), respectively. It was concluded that L. vannamei that were
      immersed in hot-water extract at 400 mg l(-1), injected with hot-water extract at
      6 microg g(-1) shrimp, and fed hot-water extract of G. amansii at 2.0 g kg(-1) or
      less showed increased immune ability as well as resistance to V. alginolyticus
      infection.

PMID- 17194606
TI  - Xenopus as a model system for vertebrate heart development.
AB  - The African clawed frog, Xenopus laevis, is a valuable model system for studies
      of vertebrate heart development. In the following review, we describe a range of
      embryological and molecular methodologies that are used in Xenopus research and
      discuss key discoveries relating to heart development that have been made using
      this model system. We also discuss how the sequence of the Xenopus tropicalis
      genome provides a valuable tool for identification of orthologous genes and for
      identification of evolutionarily conserved promoter elements. Finally, both
      forward and reverse genetic approaches are currently being applied to Xenopus for
      the study of vertebrate heart development.

PMID- 17194607
TI  - The 'Functional Muscle-Bone Unit': probing the relevance of mechanical signals
      for bone development in children and adolescents.
AB  - The present text deals with the relationship of muscle force and mass to bone
      mass and geometry in the developing skeleton of children and adolescents. Recent
      results of the last ten years are discussed with reflection on Harold Frost's
      'mechanostat hypothesis'. Bone mass and geometry follow the development of body
      size and muscle force in children and adolescents. Thereby, bone is adapted to
      the tissue strain due to biomechanical forces. This process is modified by
      hormonal signals (i.e., estrogens and androgens). Therefore, the quantified
      relationship of muscle force to bone stability is a reasonable approach to
      distinguish between primary and secondary bone diseases. Primary bone diseases
      are characterized by a disturbed adaptation of bone to biomechanical forces. In
      contrast, secondary bone diseases show a correct adaptation of bone to loaded
      forces in combination with a decline of muscle force. Therefore, the 'Functional
      Muscle-Bone Unit' was introduced into the diagnostics of pediatric bone diseases.
      The ratio of two parameters--referred to bone strength on the one and to
      biomechanical forces on the other side--is a reasonable diagnostic approach to
      distinguish between primary and secondary bone diseases.

PMID- 17194608
TI  - The effect of the Salmonella genomic island 1 on in vitro global gene expression
      in Salmonella enterica serovar Typhimurium LT2.
AB  - A Salmonella genomic island 1 (SGI1) isogenic strain pair was constructed using
      Salmonella enterica serovar Typhimurium LT2 (ST LT2). Real-time quantitative
      reverse transcriptase PCR revealed detectable mRNA transcripts for all 44
      putative ORFs encoded within the SGI1. The highest levels of transcripts observed
      in SGI1 encoded ORFs were found in genes conferring antibiotic resistance to
      ampicillin, streptomycin/spectinomycin, and sulphonamides. Abundant mRNA
      transcripts, relative to gapA, were also noted for one putative regulatory ORF
      and seven ORFs of unknown function encoded within SGI1, whose products could
      represent factors contributing to increases in virulence and/or fitness of the
      organism. DNA microarray analysis revealed the differential expression of known
      factors that contribute to virulence in many pathogens. Twenty-two chromosomal
      genes were significantly upregulated in ST LT2 harboring SGI1, which included
      increased expression of iron and sialic acid utilization genes. Decreased
      expression was noted for 15 genes in ST LT2 harboring SGI1, including genes
      involved in chemotaxis and motility. This is the first report examining gene
      expression within the SGI1, as well as its potential effect on global gene
      expression, and sets the foundation for future studies involving the effect of
      SGI1 in other Salmonella spp.

PMID- 17194609
TI  - The binding of CCL2 to the surface of Trypanosoma cruzi induces chemo-attraction
      and morphogenesis.
AB  - Adhesion of Trypanosoma cruzi to host cells employs mechanisms which are complex
      and not completely understood. Upon infection, host cells release pro
      inflammatory cytokines and chemokines in the environment. These had been found to
      be involved with increasing parasite uptake as well as killing by macrophages and
      cardiomyocytes. In the present study, we focused on the interaction of murine
      beta-chemokine CCL2 with trypomastigote forms of T. cruzi. We found that this
      chemokine directly triggers the chemotaxis and morphogenesis of trypomastigote
      forms of parasites. Binding assays showed that the interaction of CCL2 with
      molecules present in trypomastigote forms is abolished by the addition of
      condroitin 6-sulphate, a glycosaminoglycan. Moreover, we also observed that the
      parasite glycoproteins are the major players in this interaction. In summary, our
      study demonstrates a host ligand/parasite receptor interaction that may have
      relevant implications in the tissue tropism of this important parasitic disease.

PMID- 17194610
TI  - In vitro and in vivo replication of seal gammaherpesviruses in cells of multiple
      species.
AB  - Phocid herpesvirus virus type 2 (PhHV-2), a putative gammaherpesvirus of seals,
      has been isolated from harbor seals (Phoca vitulina) and grey seals (Halichoerus
      grypus). In the present study, different PhHV-2 isolates were shown to have a
      broad in vitro tropism for various cell types from several mammalian species.
      Inbred mice and two species of non-human primates proved to be susceptible to
      experimental infection with PhHV-2. The development of myoepitheliomas and spleen
      hyperplasia upon cyclosporin A treatment in some of the PhHV-2-infected animals
      warrants further investigation of the oncogenic and zoonotic potential of this
      virus.

PMID- 17194611
TI  - Lipid rafts play an important role in the early stage of severe acute respiratory
      syndrome-coronavirus life cycle.
AB  - Lipid rafts are involved in the life cycle of many viruses. In this study, we
      showed that lipid rafts also play an important role in the life cycle of severe
      acute respiratory syndrome (SARS)-coronavirus (CoV). Cholesterol depletion by
      pretreatment of Vero E6 cells with methyl-beta-cyclodextrin (MbetaCD) inhibited
      the production of SARS-CoV particles released from the infected cells. This
      inhibition was prevented by addition of cholesterol to the culture medium,
      indicating that the reduction of virus particle release was caused by the loss of
      cholesterol in the cell membrane. In contrast, cholesterol depletion at the post
      entry stage (3h post-infection) caused only a limited effect on virus particle
      release. Northern blot analysis revealed that the levels of viral mRNAs were
      significantly affected by pretreatment with MbetaCD, but not by treatment at 3h
      post-infection. Interestingly, no apparent evidence for colocalization of
      angiotensin converting enzyme 2 with lipid rafts in the membrane of Vero E6 cells
      was obtained. These results suggest that lipid rafts could contribute to SARS-CoV
      infection in the early replication process in Vero E6 cells.

PMID- 17194612
TI  - Effect of phthiocerol dimycocerosate deficiency on the transcriptional response
      of human macrophages to Mycobacterium tuberculosis.
AB  - The control of mycobacterial infections is dependent on the finely tuned
      synergism between the innate and adaptive immune responses. The macrophage is the
      major host cell for Mycobacterium tuberculosis and the degree of virulence of
      mycobacteria may influence the initial macrophage response to infection. The cell
      wall molecule, phthiocerol dimycocerosate (DIM), is an important virulence factor
      that influences the early growth of M. tuberculosis in the lungs. To explore the
      basis for this effect we have compared the early gene response of human THP-1
      macrophages to infection with virulent M. tuberculosis and the DIM-deficient
      DeltafadD26 M. tuberculosis strain using microarrays. Detailed analysis revealed
      a common core of macrophage genes, which were rapidly induced following infection
      with both strains, and deficiency of DIM had no significant effect on this
      initial macrophage transcriptional responses. In addition to chemokines and pro
      inflammatory cytokines, the early response genes included components of the Toll
      like receptor signalling, antigen presentation and apoptotic pathways, interferon
      response genes, cell surface receptors and their ligands, including TNF-related
      apoptosis inducing ligand (TRAIL) and CD40, and other novel genes. Therefore,
      although fadD26 deficiency is responsible for the early attenuation of the growth
      of M. tuberculosis in vivo, this effect is not associated with differences in the
      initial macrophage transcriptional response.

PMID- 17194613
TI  - Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk
      of malaria disease in a Tanzanian population.
AB  - Protective immunity to malaria is acquired after repeated exposure to the
      polymorphic Plasmodium falciparum parasite. Whether the number of concurrent
      antigenically diverse clones in asymptomatic infections predicts the risk of
      subsequent clinical malaria needs further understanding. We assessed the
      diversity of P. falciparum infections by merozoite surface protein 2 genotyping
      in a longitudinal population based study in Tanzania. The number of clones was
      highest in children 6-10 years and in individuals with long time to previous anti
      malarial treatment. Individual exposure, analysed by circumsporozoite protein
      antibody levels, was associated with parasite prevalence but not with the number
      of clones. The risk of subsequent clinical malaria in children free of acute
      disease or recent treatment was, compared to one clone, reduced in individuals
      with multiclonal infections or without detectable parasites, with the lowest
      hazard ratio 0.28 (95% confidence interval 0.10-0.78 Cox regression) for 2-3
      clones. The number of clones was not associated with haemoglobin levels. A
      reduced risk of malaria in asymptomatic individuals with multiclonal persistent
      P. falciparum infections suggests that controlled maintenance of diverse
      infections is important for clinical protection in continuously exposed
      individuals, and needs to be considered in the design and evaluation of new
      malaria control strategies.

PMID- 17194614
TI  - Clinical practice format for choosing a second-line disease modifying anti
      rheumatic drug in early rheumatoid arthritis after failure of 6 months' first
      line DMARD therapy.
AB  - BACKGROUND: The objective was to develop a clinical practice format for choosing
      a second-line disease-modifying anti-rheumatic drug (DMARD) after a 6-month
      course of a first-line DMARD in patients with early RA. METHODS: A panel of 34
      experts selected treatment option from various scenarios using the Thurstone
      pairwise method. The experts had to choose between two proposed DMARDs without
      proposing other options. The scenarios were obtained using the three items:
      DAS28, rheumatoid factor status and radiographic structural damage. A sample of
      240 among 480 scenarios for each expert was taken at random. Responses given by
      at least 20% of the experts were considered pertinent. RESULTS: Recommendations
      for choosing a second DMARD for early RA after failure of a 6-month course of a
      first-line DMARD were established according to 4 parameters: type of first-line
      DMARD, activity, RF status and radiographic joint damage. The results of this
      study suggest that in patients with early RA who fail a 6-month course of first
      line DMARD therapy, the best options may be addition of corticosteroid when
      disease activity is moderate to high and switching to a biologic agent when
      further radiographic joint damage occurs, particularly in patients with positive
      tests for RF. CONCLUSION: Although our scenarios did not include step-up (add
      instead of substitute) strategies, except for corticosteroids, we feel that the
      format presented here can optimise the management of patients with early RA seen
      in clinical practice.

PMID- 17194615
TI  - [Psychogenic amenorrhea].
AB  - Any amenorrhoea noticed outside pregnancy, lactation and menopause periods might
      be of organic or functional origin. Today, non organic amenorrhoea are either
      called hypothalamic amenorrhoea, more exactly supra hypothalamic amenorrhoea;
      functional amenorrhoea--this definition being characterized by its lack of any
      anatomic substratum; or, psychogenic amenorrhoea--an etiologic definition. Like
      any amenorrhoea, functional or psychogenic amenorrhoea is the consequence of
      either anovulation or endometrial hypotrophy. Neuroendocrine sciences do open new
      exciting research perspectives but other ways all the more promising since
      hormonal mechanics would not be the explanation. Work on the unconscious is
      indeed the other road leading to these psychogenic amenorrhoea. The term
      "psychogenic"--of psychological origin--does not mean of unknown origin, provided
      we recognize the strong link between psyche and soma. Treatment for this kind of
      amenorrhoea is twofold: medical and psychotherapeutic. Even though psychological
      etiology is obvious, clinical examination must be rigorous and completed by
      complementary exams which will guide the therapeutics. This is reassuring to the
      patient for the gynaecologist she chose to consult is implied, and not the
      psychotherapist. This reassures us too, because what we care for, as doctors, is
      first of all the body. Psychotherapeutic support can be provided by the general
      practitioner or the gynaecologist, both with psychosomatics training, but a
      multidisciplinary approach must often be worked out.

PMID- 17194616
TI  - The number of screws, bone quality, and friction coefficient affect acetabular
      cup stability.
AB  - One of the major causes of loosening of cementless acetabular cup implants is
      insufficient initial stability. This study used three-dimensional finite element
      models of the pelvis and acetabular components to investigate the effects of the
      number of screws, bone quality, and friction coefficient of the acetabular cup on
      the initial stability under normal walking. A commercially available
      hemispherical acetabular cup with five screw holes was used as the default model.
      The stiffness of the pelvis and the friction coefficient of the cup were
      systematically varied, within a realistic range, to assess the initial stability
      of the acetabular cup. The simulations showed that the inserted screws provide
      only a localized reduction in the relative micromotion between the cup and pelvis
      therefore inserting several screw closed together might not be useful. Changes in
      the pelvic stiffness have a non-linear effect on the initial stability of
      acetabular cup and the subchondral bone provides good support for fixation of the
      cementless cup. The friction coefficient of the acetabular cup plays a limited
      role, comparing with the factor of bone quality, in resisting relative
      micromotion in the cup-pelvis interface.

PMID- 17194617
TI  - Control of integrin genes expression in the eye.
AB  - The ending race for sequencing the human genome has left the scientists faced
      with new challenges. Indeed, now that almost every human gene has been sequenced
      and precisely positioned on the human chromosomes, one of the next, most burning
      task consist in understanding how transcription of these genes is ensured in any
      given cell. The integrins encoding genes are no exception. Integrins bridge the
      cell to the many components from the extracellular matrix (ECM), such as laminins
      (LM) and collagens, and thereby transduce intracellular signals that will alter
      many of the cell's properties such as adhesion, migration, proliferation and
      survival. As a much clearer picture of the many proteins that belong to this
      family has emerged over the last few years, tremendous efforts have been
      dedicated to the identification of the regulatory sequences that modulate their
      expression. This review provides an overview of the current state of knowledge
      about the organization of the regulatory elements and the transcription factors
      (TF) they bind that are used by the cell in order to ensure transcription of each
      of the integrins gene. A particular attention has been given to those reported to
      be expressed in the eye. It also explores how components from the ECM might
      participate in the control of integrins gene expression and establishes links to
      wound healing of the corneal epithelium, a process that transiently alter the
      composition of the basement membrane on which the epithelial cells lie.

PMID- 17194618
TI  - Pain signalling pathways: from cytokines to ion channels.
AB  - Pain is the major reason patients seek medical care. The treatment of pain,
      particularly chronic pain associated with cancer and damage to the nervous
      system, is at present inadequate. Lack of effective analgesics is partly due to
      the fact that pain signalling mechanisms are still not fully understood. Over the
      recent years, many channels, receptors, and regulatory proteins involved in pain
      pathways have bee identified, and novel pain signalling mechanisms and pathways
      at peripheral and spinal levels have been discovered. It is anticipated that
      increased understanding of the molecular mechanisms of pain would provide a hope
      for the future development of effective pain killers. This review examines the
      currently available information on the molecular aspects of pain signalling
      pathways, and discusses novel and promising therapeutic targets for the treatment
      of pain in humans.

PMID- 17194620
TI  - Allele and genotype frequencies of metabolic genes in Native Americans from
      Argentina and Paraguay.
AB  - Interethnic differences in the allele frequencies of CYP2D6, NAT2, GSTM1 and
      GSTT1 deletions have been documented for Caucasians, Asians, and Africans
      population. On the other hand, data on Amerindians are scanty and limited to a
      few populations from southern areas of South America. In this report we analyze
      the frequencies of 11 allele variants of CYP2D6 and 4 allele variants of NAT2
      genes, and the frequency of GSTM1 and GSTT1 homozygous deleted genotypes in a
      sample of 90 donors representing 8 Native American populations from Argentina and
      Paraguay, identified as Amerindians on the basis of their geographic location,
      genealogical data, mitochondrial- and Y-chromosome DNA markers. For CYP2D6, 88.6%
      of the total allele frequency corresponded to *1, *2, *4 and *10 variants.
      Average frequencies for NAT2 *4, *5, *6 and *7 alleles were 51.2%, 25%, 6.1%, and
      20.1%, respectively. GSTM1 deletion ranged from 20% to 66%, while GSTT1 deletion
      was present in four populations in less than 50%. We assume that CYP2D6 *2, *4,
      *10, *14; NAT2 *5, *7 alleles and GSTM1 and GSTT1 *0/*0 genotypes are founder
      variants brought to America by the first Asian settlers.

PMID- 17194621
TI  - Impact of noise and other factors on speech recognition in anaesthesia.
AB  - INTRODUCTION: Speech recognition is currently being deployed in medical and
      anaesthesia applications. This article is part of a project to investigate and
      further develop a prototype of a speech-input interface in Danish for an
      electronic anaesthesia patient record, to be used in real time during operations.
      OBJECTIVE: The aim of the experiment is to evaluate the relative impact of
      several factors affecting speech recognition when used in operating rooms, such
      as the type or loudness of background noises, type of microphone, type of
      recognition mode (free speech versus command mode), and type of training.
      METHODS: Eight volunteers read aloud a total of about 3600 typical short
      anaesthesia comments to be transcribed by a continuous speech recognition system.
      Background noises were collected in an operating room and reproduced. A
      regression analysis and descriptive statistics were done to evaluate the relative
      effect of various factors. RESULTS: Some factors have a major impact, such as the
      words to be recognised, the type of recognition and participants. The type of
      microphone is especially significant when combined with the type of noise. While
      loud noises in the operating room can have a predominant effect, recognition
      rates for common noises (e.g. ventilation, alarms) are only slightly below rates
      obtained in a quiet environment. Finally, a redundant architecture succeeds in
      improving the reliability of the recognitions. CONCLUSION: This study removes
      some uncertainties regarding the feasibility of introducing speech recognition
      for anaesthesia records during operations, and provides an overview of the
      interaction of several parameters that are traditionally studied separately.

PMID- 17194619
TI  - Proteomic discovery of protease substrates.
AB  - Elucidation of in vivo substrate degradomes of a protease is a daunting endeavor
      because of the large number of proteins in a proteome and often minute and
      transient amounts of key substrates. Proteomic substrate screens for proteases
      are currently experiencing impressive progress. Mass spectrometry-based global
      proteome analysis, interfaced with liquid-chromatography and together with stable
      isotope labeling strategies, has provided increased coverage and sensitivity for
      quantitative proteomics. ICAT and iTRAQ labeling have been used to identify a
      plethora of new matrix metalloproteinase substrates. Emerging techniques focus on
      the quantitative analysis of proteolytically generated neo amino-termini, which
      we call terminopes, on a system-wide basis. In vivo SILAC pulse-chase experiments
      have also enabled the study of individual protein turnover and global proteome
      dynamics in cells and whole organisms. Together with activity-based probes for
      the profiling of functional proteases, there is now in place an array of
      complementary technologies to dissect the 'protease web' and its distortion in
      pathology.

PMID- 17194623
TI  - Determining the intra- and inter-observer reliability of screening tools used in
      sports injury research.
AB  - Sports injury etiological studies explore the relationships between potential
      injury risk factors and injury outcomes. The ability of such studies to clearly
      identify intrinsic risk factors for sports injury depends on the accuracy of
      their measurement. Measurements need to be reproducible over time and repeatable
      by different observers, as well as within a given individual. The importance of
      the reliability of pre-participation screening protocols and other clinical
      assessment tools has been identified in a number of published studies. However, a
      review of these studies indicates that a variety of statistical techniques have
      been used to calculate intra- and inter-observer reliability. While the intra
      class correlation coefficient (ICC) is the most often cited measure, a range of
      statistical approaches to estimating ICCs have been used. It is therefore
      difficult to determine which statistical method is most appropriate in the
      context of measuring intrinsic risk factors in sports injury research. This paper
      summarises a statistical method for the concurrent assessment of intra- and inter
      observer reliability and presents an argument for why this approach should be
      adopted by sports injury researchers using screening protocols that collect
      continuous data.

PMID- 17194622
TI  - Comparative analytical sensitivities of six rapid influenza A antigen detection
      test kits for detection of influenza A subtypes H1N1, H3N2 and H5N1.
AB  - BACKGROUND: Rapid and simple methods for diagnosing human influenza A (H5N1)
      disease urgently needed. The limited data so far suggest that the currently
      available rapid antigen detection kits have poor clinical sensitivity for
      diagnosis of human H5N1 disease. OBJECTIVES: To compare the analytical
      sensitivity of six commercially available rapid antigen detection kits for the
      detection of "human" (subtypes H1N1, H3N2) and "avian" (subtype H5N1) influenza A
      viruses. STUDY DESIGN: Six commercially available test kits for the detection of
      influenza A were investigated. Analytic sensitivity for the detection of two
      contemporary H1N1, two H3N2 and three H5N1 viruses was determined using virus
      culture as a reference method. RESULTS AND CONCLUSIONS: Each test kit detected
      the H5N1 virus subtypes as efficiently as they detected conventional human
      viruses of subtypes H1N1 or H3N2. However, limits of detection of influenza
      viruses of all subtypes by antigen detection kits were >1000-fold lower than
      virus isolation. Thus, the reportedly poor clinical sensitivity of these antigen
      detection kits for diagnosis of patients with H5N1 disease is not due to a
      difference of sensitivity for detecting avian influenza H5N1 compared to human
      influenza viruses.

PMID- 17194624
TI  - Guidelines for the diagnosis and management of familial long QT syndrome.

PMID- 17194625
TI  - Role of the JAK-STAT pathway in myocardial injury.
AB  - Cardiovascular pathologies are an enormous burden in human health and despite the
      vast amount of research; the molecular mechanisms and pathways that control the
      underlying pathologies are still not fully appreciated. The Janus kinase (JAK)
      signal transducers and activators of transcription (STAT) pathway has recently
      been shown to be an integral part of the response of the myocardium to various
      cardiac insults, including myocardial infarction, oxidative damage, myocarditis,
      hypertrophy and remodeling, in addition to having a prominent role in
      cardioprotective therapies such as ischaemic preconditioning. Here, recent
      advances in the understanding of how the JAK-STAT pathway orchestrates the
      response to cellular damage in the myocardium are discussed, along with the
      potential benefits and challenges in manipulating this pathway in cardiovascular
      therapy.

PMID- 17194626
TI  - In silico analysis and characterization of GntR family of regulators from
      Mycobacterium tuberculosis.
AB  - The genome of Mycobacterium tuberculosis contains a large number of hypothetical
      and poorly characterized proteins including the proteins belonging to the GntR
      family. The regulators of this family show a conserved N-terminal DNA-binding
      domain but have a highly diverse C-terminal domain involved in the effector
      binding and/or oligomerization. This heterogeneity has led to a further
      classification of this family into various subfamilies. The sequence analysis of
      the M. tuberculosis genome revealed that five genes encode for FadR-like
      regulators, one gene for HutC-like regulator and one for YtrA-like regulator.
      This classification was also consistent with specific secondary structural
      features known to be associated with FadR, HutC and YtrA subfamilies. Out of the
      five FadR-like regulators three of the regulators were further subclassified into
      FadR group and two of them into the VanR group. Interestingly Rv3060c, a FadR
      like regulator, was shown to have an unusual size which led us to demonstrate it
      as a product of a gene duplication and fusion event. Thus this study extends the
      genome annotation of M. tuberculosis and provides important leads for initiating
      experimental characterization of these proteins, which in turn will enrich our
      knowledge of their role in cellular physiology.

PMID- 17194627
TI  - A rare case of biventricular non-compaction associated with ventricular septal
      defect and descendent aortic stenosis in a young man.
AB  - Non-compaction of the ventricular myocardium is a cardiomyopathy caused by the
      arrest of normal embryogenesis of the ventricles. It is classified in isolated
      non-compaction of the ventricles (most frequently of the left one) and in
      ventricular non-compaction associated with other congenital anomalies of the
      endocardium and myocardium, such as obstruction of the right or left ventricular
      outflow tracts, complex cyanotic congenital heart disease, and coronary artery
      anomalies. There are controversies regarding the right ventricle non-compaction
      due to the normally trabeculated shape of its walls. We present a case of severe
      heart failure with a complex anomaly: biventricular non-compaction, ventricular
      septal defect and aortic thoracic stenosis.

PMID- 17194629
TI  - New insights for understanding the transcription-coupled repair pathway.
AB  - Transcription-coupled repair (TCR) is a sub-pathway of nucleotide excision repair
      (NER) able to remove bulky DNA lesions located on the transcribed strands of
      active genes more rapidly than those located on the non-transcribed genomic DNA.
      Two recently published reports try to dissect the molecular mechanisms of TCR
      using simplified in vitro assays. A third report shows in vivo data that
      confirmed the in vitro ones and extends them to the role of other TCR factors
      such as those involved in chromatin remodeling. These approaches shed light on
      the interplay between stalled RNA polymerase II and NER factors necessary for
      efficient repair. Because severe diseases, such as Cockayne syndrome, are
      associated with defects or mutations in proteins required for transcription
      coupled nucleotide excision repair, complete understanding of this pathway should
      allow us to understand this disease better and eventually to propose adequate
      therapies.

PMID- 17194630
TI  - High-throughput liquid chromatographic-tandem mass spectrometric determination of
      arginine and dimethylated arginine derivatives in human and mouse plasma.
AB  - The balance between nitric oxide (NO) and vasoconstrictors like endothelin is
      essential for vascular tone and endothelial function. L-Arginine is converted to
      NO and L-citrulline by NO synthase (NOS). Asymmetric dimethylarginine (ADMA) and
      symmetric dimethylarginine (SDMA) are endogenous inhibitors of NO formation. ADMA
      is degraded by dimethylamino dimethylhydrolases (DDAHs), while SDMA is
      exclusively eliminated by the kidney. In the present article we report a LC
      tandem MS method for the simultaneous determination of arginine, ADMA, and SDMA
      in plasma. This method is designed for high sample throughput of only 20-mul
      aliquots of human or mouse plasma. The analysis time is reduced to 1.6 min by LC
      tandem MS electrospray ionisation (ESI) in the positive mode. The mean plasma
      levels of l-arginine, ADMA, and SDMA were 74+/-19 (SD), 0.46+/-0.09, and 0.37+/
      0.07 microM in healthy humans (n=85), respectively, and 44+/-14, 0.72+/-0.23, and
      0.19+/-0.06 microM in C57BL/6 mice. Also, the molar ratios of arginine to ADMA
      were different in man and mice, i.e. 166+/-50 and 85+/-22, respectively.

PMID- 17194628
TI  - Transcriptional regulation of the Drosophila melanogaster muscle myosin heavy
      chain gene.
AB  - We show that a 2.6kb fragment of the muscle myosin heavy-chain gene (Mhc) of
      Drosophila melanogaster (containing 458 base pairs of upstream sequence, the
      first exon, the first intron and the beginning of the second exon) drives
      expression in all muscles. Comparison of the minimal promoter to Mhc genes of 10
      Drosophila species identified putative regulatory elements in the upstream region
      and in the first intron. The first intron is required for expression in four
      small cells of the tergal depressor of the trochanter (jump) muscle and in the
      indirect flight muscle. The 3'-end of this intron is important for Mhc
      transcription in embryonic body wall muscle and contains AT-rich elements that
      are protected from DNase I digestion by nuclear proteins of Drosophila embryos.
      Sequences responsible for expression in embryonic, adult body wall and adult head
      muscles are present both within and outside the intron. Elements important for
      expression in leg muscles and in the large cells of the jump muscle flank the
      intron. We conclude that multiple transcriptional regulatory elements are
      responsible for Mhc expression in specific sets of Drosophila muscles.

PMID- 17194632
TI  - A rare cause of obscure gastrointestinal bleeding: an anastomotic enteric varix
      not associated with portal hypertension.

PMID- 17194631
TI  - Determination of meperidine, tramadol and oxycodone in human oral fluid using
      solid phase extraction and gas chromatography-mass spectrometry.
AB  - Analytical procedures for the determination of meperidine, tramadol and oxycodone
      in oral fluid have been developed and validated using gas chromatography-mass
      spectrometry (GC/MS) following initial screening with enzyme linked immunosorbent
      assay (ELISA). The oral fluid samples were collected using the Quantisal device,
      and any drugs present were quantified using mixed mode solid-phase extraction and
      electron impact GC/MS. For confirmation, three ions were monitored and two ion
      ratios determined, which were within 20% of those of the known calibration
      standards. The limits of quantitation were 10 ng/mL; the intra-day precision of
      the assays (n=5) was 2.33%, 1.00% and 7.61%; inter-day precision 2.48%, 2.44% and
      5.8% (n=10) for meperidine, tramadol and oxycodone, respectively. The percentage
      recovery of the drugs from the collection pads was 86.7%, 87.7% and 96.6%,
      respectively (n=6). The methods were applied to specimens obtained during
      research studies in the USA.

PMID- 17194633
TI  - Array-CGH analysis and clinical description of 2q37.3 de novo subtelomeric
      deletion.
AB  - We report on a 13-year-old girl with normal karyotype and a de novo cryptic
      terminal deletion of chromosome 2q, detected by subtelomeric FISH analysis.
      Further investigation with array-CGH analysis using the 1Mb resolution Spectral
      Chip 2600 (Spectral Genomics) confirmed the deletion and also showed a deletion
      of four additional clones. No other abnormalities were detected by array-CGH.
      FISH studies using 8 BAC-probes were performed for fine mapping of the deletion
      and confirmed the array results. FISH analysis showed that the deletion
      breakpoint lies between clones RP11-84G18 and RP11-83N2 (physical distance
      between clones 0.36Mb) and extends to the telomere. The size of the deletion was
      estimated to be about 6.4-6.7Mb. Clinical findings include: developmental delay,
      severe behavioural disturbances, growth-pubertal retardation, congenital
      conductive mild hearing loss, growth hormone deficiency, compensate
      hypothyroidism, dysmorphic facial features, excessive joint hypermobility,
      brachymetaphalangy, abnormal dermatoglyphics and a history of neonatal
      laryngomalacia, hypotonia and umbilical hernia. The phenotype of our patient is
      in keeping with those of the literature, with the exception of cardiovascular,
      urogenital, neurological anomalies and eczema, which were not observed. The
      report of the clinical and molecular presentation of similar cases will allow
      accurate phenotype-genotype correlation and proper genetic counseling of the
      family.

PMID- 17194634
TI  - Genetic impact of TNF-beta on risk factors for coronary atherosclerosis.
AB  - BACKGROUND: Inflammatory processes are considered to play an important role in
      the development of coronary atherosclerosis. The proinflammatory cytokine, tumor
      necrosis factor beta (TNF-beta), is thought to contribute to the pathogenesis of
      atherosclerosis. STUDY DESIGN: In this clinical study, the influence of genetic
      variants of TNF-beta (c.7G>A, IVS1+90G>A, C13R, T60N) on major coronary risk
      factors, including gender, smoking, history of cardiovascular diseases,
      biochemical data (inflammatory markers, factors of lipid metabolism,
      coagulation/fibrinolysis balance), and angiographically-proven coronary state,
      was investigated in 176 European Caucasian probands (130 males, mean age: 51.9 +/
      8.9 y). RESULTS: The most frequent combinations of the polymorphisms
      investigated were significantly associated with four of the coronary risk factors
      evaluated: hypertension, body mass index, the common inflammatory marker TNF
      alpha (mRNA expression), and fibrinogen (p < 0.05). However, on testing the
      impact of the genetic background on the incidence of coronary stenosis in this
      sample of European Caucasians, no significant influence of these polymorphisms
      (stepwise binary logistic regression analysis) could be proven. These findings
      emphasise a distinct influence of TNF-beta polymorphisms on important modulators
      of the development of coronary atherosclerosis, but exclude its genetic
      background, investigated in this study as an independent coronary risk factor.

PMID- 17194635
TI  - Chemokines in proliferative diabetic retinopathy and proliferative
      vitreoretinopathy.
AB  - PURPOSE: To determine levels of the chemokines CCL1/I-309, CCL2/MCP-1, CCL3/MIP
      1alpha, CCL4/MIP-1beta, CCL7/MCP-3, CCL8/MCP-2, CXCL5/ENA-78, CXCL6/GCP-2,
      CXCL10/IP-10, and CXCL11/I-TAC in the vitreous humor and serum, from patients
      with proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy
      (PVR), and rhegmatogenous retinal detachment with no PVR (RD), and to investigate
      the expression of MCP-1, CXCL12/SDF-1, and the chemokine receptor CXCR3 in
      epiretinal membranes. METHODS: Paired vitreous humor and serum samples were
      obtained from patients undergoing vitrectomy for the treatment of RD (57
      specimens), PVR (32 specimens), and PDR (88 specimens). The levels of chemokines
      were measured by enzyme-linked immunosorbent assays. Eighteen PDR and 5 PVR
      membranes were studied by immunohistochemical techniques. RESULTS: Of all the
      chemokines studied, only MCP-1 and IP-10 were detected in vitreous humor samples.
      MCP-1 levels in vitreous humor samples were significantly higher than in serum
      samples (p < 0.001). MCP-1 levels were significantly higher in vitreous humor
      samples from patients with PVR and PDR compared with RD (p = 0.0002). MCP-1
      levels in vitreous humor samples from patients with active PDR were significantly
      higher than in inactive PDR cases (p = 0.0224). IP-10 levels in vitreous humor
      samples were significantly higher than in serum samples (p = 0.0035). IP-10
      levels were significantly higher in vitreous humor samples from patients with PVR
      and PDR compared with RD (p = 0.0083). The incidence of IP-10 detection in
      vitreous humor samples was significantly higher in active PDR cases compared with
      inactive cases (p = 0.0214). There was a significant association between the
      incidence of IP-10 detection and increased levels of MCP-1 in vitreous humor
      samples from all patients, and patients with RD and PDR (p < 0.001 for all
      comparisons). MCP-1, and SDF-1 were localized in myofibroblasts in PVR and PDR
      membranes and in vascular endothelial cells in PDR membranes. CXCR3 was expressed
      by vascular endothelial cells in PDR membranes. CONCLUSION: MCP-1, IP-10 and SDF
      1 may participate in pathogenesis of PVR and PDR. Myofibroblasts and vascular
      endothelial cells are the major cell types expressing MCP-1, SDF-1, and CXCR3 in
      epiretinal membranes.

PMID- 17194636
TI  - Association between serum free IGF-I and IGFBP-3 levels in type-I diabetes
      patients affected with associated autoimmune diseases or diabetic complications.
AB  - BACKGROUND: Patients with type 1 diabetes (T1DM) present lower serum free IGF and
      IGFBP-3 values than healthy people. T1DM patients often present with associated
      autoimmune diseases such as thyroiditis or coeliac disease, and over time they
      frequently develop proliferative retinopathy, neuropathy or nephropathy in
      different combinations. OBJECTIVE: The aim of this study was to evaluate the
      effect of two associated autoimmune diseases or three diabetic complications on
      the serum free IGF-I or IGFBP-3 levels in T1DM patients, who also have a family
      history of T1DM. Design. 246 T1DM patients were enrolled, and then subdivided
      into groups according to diabetic complications or associated autoimmune
      diseases. Demographic and clinical data were recorded. Serum free IGF-I and IGFBP
      3 levels were determined by IRMA. RESULTS: IGF-I and IGFBP-3 generally present
      correlated serum values as confirmed in this study. Those patients with
      autoimmune thyroiditis and coeliac disease presented with significantly lower
      serum values of IGFBP-3, whereas free IGF-I was significantly lower in patients
      with the different diabetic complications. Retinopathy presented a slightly
      significant reduction in serum free IGF-I, while neuropathy and nephropathy
      showed a more pronounced fall. The number of complications was related to
      progressively decreasing free IGF-I levels. T1DM family history was associated
      with lower serum free IGF-I concentrations. These findings were confirmed after
      correction for age, glycosylated haemoglobin levels, insulin treatment protocol,
      body mass index, serum creatinine and sex. CONCLUSION: Despite a direct
      correlation between serum free IGF-I and IGFBP-3, the correlation between the two
      molecules in patients with associated autoimmune diseases was lost, possibly due
      to different mechanisms of metabolic regulation.

PMID- 17194637
TI  - Increase in annexin V-positive B cells expressing LILRB1/ILT2/CD85j in malaria.
AB  - The outcome of a Plasmodium falciparum infection differs greatly between
      patients, ranging from an asymptomatic carrier status to the most severe
      characteristics influenced by activating and inhibiting immune factors. The
      inhibitory leukocyte immunoglobulin-like receptor (LILRB1/CD85j) plays an
      important role in the immune response as regulator of cytotoxic T cells and of
      premature activation and clonal expansion of B cells. To investigate its role in
      malaria, we analyzed blood samples from malaria patients by cytometric analysis.
      We found a similar expression pattern of CD85j on PBMC in both patients and
      healthy children. However, malaria patients presented significantly more CD85j+
      CD19+ B cells, which also bound annexin V an indicator of early cell death. We
      compared the plasma levels of several cytokines, since it was speculated that
      CD85j expression influences cytokine release. Production of inflammatory
      cytokines was significantly increased in severe malaria cases. We suggest that in
      malaria, dying B cells contribute to the overwhelming cytokine release and the
      impairment of the immune memory.

PMID- 17194638
TI  - Interleukin 6 polymorphism corresponds to the number of severely stenosed
      coronary arteries.
AB  - IL6 gene promoter polymorphisms may influence the outcome of cardiovascular
      diseases. The aim of our study was to find out whether the -174G>C polymorphism,
      as well as the IL6 secretory profile, may be linked to the number of severely (>
      or = 75%) occluded coronary arteries in patients with advanced coronary heart
      disease (CHD). Three hundred and twenty patients awaiting elective coronary
      artery bypass grafting were enrolled into the study. Blood was taken the day
      before surgery. The PCR-RFLP method was used for IL6 gene polymorphism analysis.
      Spontaneous IL6 release was measured by bioassay in supernatants of whole blood
      cell cultures (WBCC) incubated for 24 h and 48 h. We found that significantly
      more patients with triple vessel disease were found within the -174GG group as
      compared to the -174GC and CC genotype carriers. The highest IL6 serum levels
      were found in the -174GG and the lowest in the -174CC genotype patients.
      Spontaneous in vitro IL6 secretion appeared to be significantly higher at all
      time points in the -174GG as compared to the CC and GC genotype carriers. The
      serum concentration of IL6 and the spontaneous IL6 secretion were directly
      related to the number of obstructed coronary vessels. Our results emphasize the
      role of IL6 as an important, non-classical risk factor predicting the number of
      severely affected coronary vessels.

PMID- 17194639
TI  - Resistin overexpression impaired glucose tolerance in hepatocytes.
AB  - Resistin is a 12.5-kDa cysteine-rich protein secreted from adipose tissue and is
      an important factor linking obesity with insulin resistance. Here, we
      investigated the effect of resistin on glucose tolerance in adult human
      hepatocytes (L-02 cells). In this study, resistin cDNA was transfected into L-02
      cells, and glucose concentration and glucokinase activity were determined
      subsequently. The data indicated resistin impaired, insulin-stimulated glucose
      utilization, which implied liver was a target tissue of resistin. To understand
      its molecular mechanism, mRNA levels of key genes in glucose metabolism and
      insulin signaling pathway were analyzed. The results demonstrated resistin
      stimulated expression of glucose-6-phosphatase (G6Pase), sterol regulatory
      element-binding protein 1c (SREBP1c) and suppressor of cytokine signaling 3 (SOCS
      3), repressed expression of peroxisome proliferator-activated receptor gamma
      (PPARgamma) as well as insulin receptor substrate 2 (IRS-2). Given that
      glucokinase (GK) activity and glucose transporter 2 (GLUT2) expression were not
      altered, we presumed that resistin did not effect them. Moreover, resistin
      lowered mRNA levels of IRS-2 while stimulating SOCS-3 expression, which suggests
      it impairs glucose tolerance by blocking the insulin signal transduction pathway.

PMID- 17194640
TI  - TNF-alpha, soluble TNF receptor and interleukin-6 plasma levels in the general
      population.
AB  - The cytokines tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors p55
      and p75, and interleukin 6 (IL-6) are involved in host defense against several
      microbiological agents, in the process of inflammation and also in body weight
      regulation. In the present study, we sought to assess the influence of age,
      gender, smoking, and body mass index on plasma levels of TNF-alpha, TNF
      receptors, and IL-6 in more than 550 adult subjects randomly selected from the
      Bavarian population. None of the cytokine parameters had a normal distribution
      and all distributions were significantly skewed. The cytokine plasma levels
      investigated increased significantly with age, while gender had a relatively
      weaker influence on the plasma levels. Plasma levels of TNF-alpha, TNF receptors,
      and IL-6 correlated significantly with the BMI. The study provides insights into
      factors influencing the cytokine levels investigated in a randomly chosen study
      sample.

PMID- 17194641
TI  - Relationship between angiogenesis and inflammation in experimental arthritis.
AB  - Background. Angiogenesis is involved in rheumatoid arthritis (RA) leading to
      leucocyte recruitment and inflammation in the synovium. Furthermore, synovial
      inflammation itself further potentiates endothelial proliferation and
      angiogenesis. In this study, we aimed at evaluating the reciprocical relationship
      between synovial inflammation and angiogenesis in a RA model, namely collagen
      induced arthritis (CIA). Methods. CIA was induced by immunization of DBA/1 mice
      with collagen type II in adjuvant. Endothelial cells were detected using a GSL-1
      lectin-specific immunohistochemical staining on knee joint sections.
      Angiogenesis, clinical scores and histological signs of arthritis were evaluated
      from the induction of CIA until the end of the experiment. Angiogenesis was
      quantified by counting both the isolated endothelial cells and vessels stained on
      each section. To evaluate the effect of increased angiogenesis on CIA, VEGF gene
      transfer was performed using an adeno-associated virus encoding VEGF (AAV-VEGF),
      by intra-muscular or intra-articular injection in mice with CIA. Results. We
      showed an increase in synovial angiogenesis from day 6 to day 55 after CIA
      induction, and, moreover, joint vascularization and clinical scores of arthritis
      were correlated (p < 0.0001, r = 0.61). Vascularization and histological scores
      were also correlated (p = 0.0006, r = 0.51). Systemic VEGF overexpression in mice
      with CIA was followed by an aggravation of arthritis as compared to AAV-lacZ
      control group (p < 0.0001). In contrast, there was no difference in clinical
      scores between control mice and mice injected within the knee with AAV-VEGF, even
      if joint vascularization was higher in this group than in all other groups (p =
      0,05 versus non-injected group). Intra-articular AAV-VEGF injections induced more
      severe signs of histological inflammation and bone destruction than AAV-Lac Z or
      no injection. Conclusion. Angiogenesis and joint inflammation evolve in parallel
      during collagen-induced arthritis. Furthermore, this work shows that exogenous
      VEGF can aggravate CIA. It is direct evidence that the increase in joint
      vascularization leads to an exacerbation of arthritis. Taken together, these
      results emphasize the role of angiogenesis in inflammatory arthritis. It also
      suggests an early involvement of angiogenesis in joint inflammation.

PMID- 17194642
TI  - Review: Negative regulation of leptin receptor signalling.
AB  - Leptin was discovered as an adipostat, regulating body weight by balancing food
      intake and energy expenditure. Recently, leptin emerged as a pleiotropic
      cytokine. It plays a substantial role in a wide spectrum of other functions
      including immune regulation, bone formation and fertility. Leptin signalling is
      under tight control. Aberrations of this stringent control system may be
      implicated in a variety of pathologies. Here, we review the various mechanisms
      that control cellular leptin receptor signalling.

PMID- 17194644
TI  - [Pain and dementia].
AB  - Dementia and pain are both common in the elderly and then frequently associated.
      The literature review shows that pain in dementia is underdiagnosed and
      consequently undertreated. This can be linked to: 1) the difficulty of pain
      assessment in patients with cognitive disorders and altered communication skills;
      2) changes of pain processing and especially in the motivational-affective
      domain; 3) modified efficacy of analgesic drugs. This has been documented in
      Alzheimer's disease but remains to be investigated in the other types of dementia
      in order that all patients can be treated whatever their diagnosis, illness
      duration and type of pain (acute versus chronic).

PMID- 17194645
TI  - [Pain and palliative care. Comments by a witness].
AB  - Physical pain is well analysed by medical science, but still often neglected by
      the practicians. It is entangled with moral suffering at the end of life. The
      distinction between these two fundamental experiences is difficult but necessary
      for the care of patients. The concept of palliative care is far from being
      integrated by health professionals as well as by everybody, because it questions
      our finitude, the signification of life and human solidarity.

PMID- 17194647
TI  - [On evaluation of psychotherapy in Alzheimer's disease].
AB  - After the recent issue of a randomised controlled trial on brief psychotherapy in
      Alzheimer's disease, we discuss the ANAES's recent report on non pharmacological
      intervention in this disease. We suggest that any evaluation must take into
      account the complex reality of the patient's and carer's needs, especially
      according to the progress of the disease. We give examples of proofs of another
      kind than those applied with cognitive therapy.

PMID- 17194646
TI  - [Tauopathy and Alzheimer disease: a full degenerating process].
AB  - Neurofibrillary degeneration is well correlated to the clinical signs of
      Alzheimer disease. However, the amyloid cascade is so well established in the
      scientific and medical community that the role of neurofibrillary degeneration in
      Alzheimer's disease etiopathogenesis is often underestimated. However, neuronal
      vulnerability is clearly a key factor for facilitating the amyloid pathology
      which allows the propagation of the degenerating process. In the present work,
      the role of tau pathology as both diagnostic marker and therapeutic target is
      highlighted in Alzheimer disease and related disorders.

PMID- 17194648
TI  - [Relationships between weight loss and circulating cytokines in patients with
      Alzheimer's disease].
AB  - 106 consecutive patients with Alzheimer's disease living in the community were
      examined in a memory clinic from a neurological department. They were screened
      for weight loss over the last 2 years. Age, duration of the disease, behavioral
      disorders, mini mental status examination, body mass index were recorded. Tumor
      necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), interleukin 6 (IL
      6) and interleukin 2 (IL-2) blood levels were measured. Weight loss was reported
      in 42.5% of the patients. TNFalpha levels were significantly higher in these
      patients (18.8 versus 15.8 pg/mL; p=0.04) than in patients without weight loss.
      Weight loss was also associated with a lower MMSE score (16.9 versus 19.3;
      p=0.03), current pacing (20% versus 1.6%; p=0.002), and hallucinations (20.0%
      versus 3.3%; p=0.008). The levels of the other cytokines did not differ between
      the patients with and without weight loss. Our findings suggest an association
      between high levels of circulating TNFalpha and unexplained weight loss in
      Alzheimer's disease.

PMID- 17194649
TI  - [Stress and aging. A counter-cultural development of locus of control and coping
      behavior in the elderly].
AB  - Large international comparative surveys showed that study of intra-cultural
      differences and of their modifications with aging could be a fertile way to
      understand the influence of culture on psychological processes. People who
      attribute what happens to them to internal and controllable causes use more
      coping strategies focused on the problem than people who put forward external
      causes. Results obtained on child and adult in occidental societies showed
      dominant tendencies towards the norm of internality and coping focused on problem
      solving. We assumed the converse hypothesis of a decreasing belief in the
      internal control and a recentering coping behavior on emotional regulation in the
      elderly, which results in an increasing maladjustment to dominant intracultural
      tendencies. We studied 215 French elderly subjects with a French scale assessing
      the type l locus of control (internal versus external) through 7 sources of
      reinforcement and with the French validation of the Vitaliano et al. coping scale
      assessing the strategies of adaptation (focused on problem solving versus on
      emotional control). The results showed that advancing age, contrary to the main
      intracultural injunctions, was linked to an increasing belief in external factors
      regulating life events and with an emotion focused coping of avoidance type when
      facing a recent stress. Unlike to the continuous emphasis, in our individualistic
      cultures, on the adaptation of the world to the self involving problem solving,
      it is the adaptation of the self to the world by managing the feelings,
      characteristic of collectivist cultures, which seems gradually to prevail during
      aging and could contribute to difficulties in adjustment of the elderly.

PMID- 17194650
TI  - [Using the SHiPA with the elderly: a person-centered approach].
AB  - Qualitative differences in control, distance and relationship with other people
      were examined using multidimensional and configurational analyses with data from
      the SHiPA. The SHiPA, developed by Bouisson (2005), contributes to inform on
      psychological functioning the elderly, using open responses, no limited into
      choices, and assesses some aspects of distress and adaptative resources in common
      daily life events that are frequently causes of difficulties. Based on scores in
      differential weighting of SHiPA dimensions, multivariate analyses revealed five
      psychological functioning profiles, characterized by anxiety, depression,
      cognition, internality, satisfaction with life, and routinization levels. Analyse
      of the differences between SHiPA profiles suggested a first discrimination
      depending on the individuals, psychological resources level, and the situation of
      subjects in third and fourth age.

PMID- 17194652
TI  - Sudden sensorineural hearing loss and antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is the association between the presence of
      antiphospholipid antibodies, thrombosis and/or pregnancy morbidity and mortality.
      This report presents two cases of antiphospholipid antibodies and sensorineural
      hearing loss and discusses the probable causative link. We recommend that
      patients presenting with sudden sensorineural hearing loss are investigated for
      evidence of antiphospholipid antibodies. Life long anticoagulation is necessary
      to prevent life threatening thrombotic or thromboembolic events.

PMID- 17194651
TI  - Parathyroid-hormone-related-protein-associated hypercalcemia in a patient with
      CLL-type low-grade leukemic B-cell lymphoma.
AB  - Humoral hypercalcemia of malignancy is a common metabolic disturbance associated
      with solid tumors, but it also occurs in lymphoma patients. Among these, low
      grade B-cell lymphoma accounts for only few cases, in which secretion of
      parathyroid hormone-related protein (PTHrP) remains even exceptional. We report
      the very rare case of a patient with a CLL type low grade leukemic B-cell
      lymphoma showing PTHrP-related hypercalcemia without evidence of bone lesions.
      Using immunohistochemistry, we demonstrate the cytoplasmic expression of PTHrP by
      the lymphoma cells in the bone marrow obtained at the onset of hypercalcemia. We
      postulate a pathogenetic role of leukemic cell production and secretion of PTHrP
      in hypercalcemia in low grade leukemic B-cell lymphoma.

PMID- 17194653
TI  - Oligoclonal T cell expansion in blood but not in the thymus from a patient with
      thymoma-associated pure red cell aplasia.
AB  - Despite the well-known association between thymoma and PRCA, the role of thymoma
      remains uncertain. There is accumulating evidence that clonal T cells are
      involved in acquired PRCA. We examined T cell receptor repertoires in blood and
      thymus from a patient with PRCA associated with thymoma and myasthenia gravis.
      Oligoclonal expansions of Vdelta1- and Vbeta1-expressing T cells were found in
      peripheral blood, whereas the repertoires of Vdelta1+ and Vbeta1+ T cells in
      thymoma were not skewed. Oligoclonal expansion of Vdelta1-expressing T cells
      remained unchanged after thymectomy. Thymus may not be the site of clonal T cell
      expansion in thymoma-associated PRCA.

PMID- 17194654
TI  - Childhood CD4+/CD56+ hematodermic neoplasm: case report and review of the
      literature.
AB  - Recently, rare CD4+/CD56+ hematodermic neoplasm has been described as a distinct
      clinico-pathologic entity, with aggressive course and poor outcome. Skin is
      typically involved at presentation, but widespread dissemination to bone marrow
      is rapid. To date, no standardized therapeutic approach to this disease has been
      established. As its diffusion mainly concerns elderly patients, only a few
      paediatric cases have been documented. We report an additional case of CD4+/CD56+
      hematodermic tumour that showed a good response to chemotherapy based on a
      lymphoma protocol. Moreover, we try to analyse features and outcome of a few
      other paediatric CD4+/CD56+ hematodermic tumours as they are reported in the
      literature.

PMID- 17194655
TI  - Progressive bicytopenia due to persistent parvovirus B19 infection after
      immunochemotherapy with fludarabine/cyclophosphamide and rituximab for relapsed B
      cell lymphoma.
AB  - Human parvovirus B 19 is known as a virus causing erythema infectiosum,
      arthropathy, transient aplastic crisis and intrauterine fetal death. Healthy
      hosts are able to clear the virus within weeks after infection. There are a few
      reports available in the literature regarding immunocompromised renal transplant
      recipients with persistent infection without seroconversion. Herein, we describe
      a 56-year old woman with a relapse of grade II follicular lymphoma who received a
      combined immunochemotherapy of rituximab, fludarabine and cyclophosphamide and
      subsequently developed a persistent parvovirus B19 infection. In the absence of
      serum immunoglobulin antibodies, PCR analysis of peripheral blood and bone marrow
      aspirate were positive for parvovirus B19. Treatment with IVIG treatment resulted
      in normalization of peripheral blood counts within 7 weeks.

PMID- 17194656
TI  - Recurrent hypoglycemia and hypothermia in a patient with Hodgkin's disease.
AB  - A 60-year-old woman presented to her primary care physician with fatigue and
      anemia. Laboratory evaluation revealed a hemoglobin level of 9.8 g/dL and an
      erythrocyte sedimentation rate (ESR) of 64 mm/hour. She subsequently developed
      nocturnal episodes of diaphoresis, confusion, and hypothermia. Capillary glucose
      measurements during the spells revealed hypoglycemia. During two supervised
      fasts, the patient's plasma glucose levels fell to 35 mg/dL and 32 mg/dL,
      respectively. Plasma insulin and C-peptide levels were appropriately suppressed,
      but a low concentration of beta-hydroxy-butyrate and normal increase of plasma
      glucose concentration after a glucagon injection suggested the presence of an
      insulin-like substance. Computed tomographic (CT) scan of the abdomen and
      subsequent positron emission tomographic (PET) scan revealed extensive
      lymphadenopathy. Biopsy of periaortic lymph nodes revealed Hodgkin's disease of
      the mixed cellularity type. Following chemotherapy, a complete remission ensued,
      the spells abated, and hypoglycemia was not induced by a 23-hour fast. We believe
      that the patient's Hodgkin's disease was producing an insulin-like substance. The
      observations of others suggest that this substance may be an autoantibody to the
      insulin receptor.

PMID- 17194657
TI  - Mucormycosis in a patient with low risk myelodysplasia treated with anti-TNF
      alpha.
AB  - Accelerated programmed cell death or apoptosis appears to play an important role
      in the pathogenesis of myelodysplasia. As overexpression of TNF-alpha has been
      described to induce cell death in myelodysplasia, treatment with anti-TNF-alpha
      is currently being explored. Caution is needed because of an increased risk of
      opportunistic infection during anti-TNF-alpha treatment. We here describe a
      patient who was treated with anti-TNF-alpha for low risk myelodysplasia and died
      of invasive mucormycosis.

PMID- 17194658
TI  - Dramatic clinical efficacy of cladribine in Rosai-Dorfman disease and evolution
      of the cytokine profile: towards a new therapeutic approach.
AB  - Rosai-Dorfman disease (RDD) is a rare disorder, often benign but with possible
      life-threatening prognosis. In most cases, specific treatment is not necessary;
      when required, the management of RDD is not codified to date, and various
      chemotherapies have been shown to be ineffective. Here, we report a patient with
      RDD who presented a dramatic and sustained response with cladribine. Analysis of
      the cytokine profile evolution shows a clear correlation between serum levels of
      TNF-alpha and IL-6 and disease activity. Our findings show the promising efficacy
      of cladribine and suggest that therapies targeting specifically cytokines might
      be useful in some cases of active RDD.

PMID- 17194659
TI  - Long-term follow-up of autologous peripheral blood stem cell transplantation in
      the treatment of a patient with acute panmyelosis with myelofibrosis.

PMID- 17194660
TI  - PET-imaging as a useful tool for early detection of the relapse site in the
      management of primary myeloid sarcoma.

PMID- 17194661
TI  - Anaplastic large cell lymphoma with involvement of the pancreas presenting as
      panniculitis in a patient with a history of acute myeloid leukemia--case report
      and review of the literature.
AB  - A 66-year-old man with history of acute myeloid leukemia (AML) presented with B
      symptoms and abdominal pain. A CT scan of the abdomen demonstrated an enlargement
      of the head and uncinate of pancreas and diffuse lymphadenopathy. The patient
      developed respiratory distress and expired. An autopsy of the pancreas revealed
      clusters of large, atypical cells, which morphologically and immunophenotypically
      were consistent with CD30 positive, ALK-negative anaplastic large cell lymphoma
      (ALCL) of T-cell lineage and multifocal fat necrosis (panniculitis) in the
      peripancreatic adipose tissue. This is the first case of ALCL of the pancreas and
      panniculitis in a patient with history of AML.

PMID- 17194662
TI  - Beta thalassemia IVS-I-5(G-->C) heterozygosity masked by the presence of HbJ
      Meerut in a Dutch-Indian patient.
AB  - We describe the genotype/phenotype correlation in a 35 year old anemic female
      referred to our laboratory because a fast eluting minor fraction on HPLC, mild
      hemolysis and hematological parameters suggesting a Thalassemia trait, eventually
      in combination with iron depletion. Direct sequencing of the alpha globin genes
      revealed heterozygosity for HbJ-Meerut, a Glu-->Ala substitution at residue 120
      not justifying the hematological parameters. No other point mutations were found
      on the alpha genes and Gap-PCR excluded the 6 common deletion defects. Direct
      sequencing of the beta-globin genes revealed the IVS-I-5 (G-->C) transversion in
      absence of the elevated HbA2 levels usually measured in carriers of this beta
      Thalassemia mutation. The HbA2 tetramer in the presence of HbJ-Meerut divides in
      two parts. One alphaN2/delta2 migrating on the right spot on HPLC. The other
      alphaJ2/delta2 migrating under the HbA fraction. Classic alkaline electrophoresis
      and the modern capillary electrophoresis CE showed these two tetramers and the
      reduction of the elevated HbA2 level of the beta-Thalassemia trait by at least
      20% due to HbA2 Meerut.

PMID- 17194663
TI  - MPL W515 and JAK2 V617 mutation analysis in patients with refractory anemia with
      ringed sideroblasts and an elevated platelet count.
AB  - Discovery of a constitutively activating point mutation of the Janus kinase 2
      (JAK2) receptor-associated tyrosine kinase in patients with polycythemia vera
      (PV) and other BCR/ABL-negative myeloproliferative disorders prompted many groups
      around the world to examine diverse subsets of patients with myeloid diseases for
      the prevalence of the JAK2 V617F mutation and its clinical and pathological
      associations.

PMID- 17194664
TI  - Favourable outcome in an APL patient with PLZF/RARalpha fusion gene: quantitative
      real-time RT-PCR confirms molecular response.
AB  - Rare cases of acute promyelocytic leukemia (APL) are associated with a t(11;17)
      translocation and a PLZF-RARalpha fusion transcript. Because of molecular
      specificities of the fusion protein, ATRA efficiency is often reduced in these
      cases. We present herein the case of an 83-year old patient which has been
      successfully treated by ATRA and Daunorubicin. The described quantitative RT-PCR
      method allowed successful monitoring and confirmation of the molecular response.

PMID- 17194665
TI  - Paraneoplastic stiff-person syndrome, heterotopic soft tissue ossification and
      gonarthritis in a HLA B27-positive woman preceding the diagnosis of Hodgkin's
      lymphoma.
AB  - Paraneoplastic neurologic syndromes associated with Hodgkin's lymphoma include
      the stiff-person syndrome. A case of stiff-person syndrome is reported who first
      presented with muscular hyperactivity and acute respiratory failure followed by
      heterotopic soft tissue ossification and acute seronegative gonarthitis. Initial
      improvement of a tetanus-like clinical picture was achieved with benzodiazepam
      given by continuous infusion for analgo-sedation to mechanically ventilate the
      patient followed by baclofen after successful weaning. The patient was HLA B27
      positive and on conventional testing no autoantibodies were detected including
      anti-glutamic acid decarboxylase antibodies (anti-GAD). Months later in the
      absence of signs of stiff-person syndrome, mediastinal lymphadenopathy and
      pleural effusions developed which were diagnosed as classical Hodgkin's lymphoma
      that was successfully treated with polychemotherapy. No relapse of paraneoplastic
      neurologic syndromes was seen after two years of lymphoma remission. The case
      illustrates that stiff-person syndrome may precede the clinical appearance of
      symptomatic Hodgkin's lymphoma.

PMID- 17194666
TI  - Intracranial hemorrhage in a term newborn with severe von Willebrand disease type
      3 associated with sinus venous thrombosis.
AB  - Intracranial hemorrhage of term neonates with severe von Willebrand disease type
      3 and near normal delivery have not been published to date. We report on a term
      newborn with severe type 3 VWD who suffered a large intracranial bleeding
      presumably subsequent to sinus venous thrombosis. This case is remarkable in two
      aspects: i) with respect to the low risk of perinatal intracranial hemorrhage
      even in neonates with VWD type 3 and ii) since VWD type 3 with factor VIII:C
      levels < 5 IU/dl does not seem to protect from thromboembolism. Guidelines for
      the management of hemophilia advise atraumatic delivery of neonates with known or
      suspected bleeding disorders, however primary caesarean section in the absence of
      complications is not obligatory. To answer the question whether the presented
      case could have an impact on the recommended management we carried out a
      worldwide survey including 24 participating specialized centers. Except a single
      case from Sweden of a female neonate with VWD type 3 who also had an inhibitor
      against VWF no further cases were reported to us. We conclude that CNS bleeding
      in term neonates with severe VWD type 3 is a rare event that requires additional
      risk factors for manifestation. Therefore, the amendment of current guidelines
      does not seem to be mandatory.

PMID- 17194667
TI  - Common variable immunodeficiency patient with large granular lymphocytosis
      developing extranodal diffuse large B-cell lymphoma: a case report.
AB  - Here we describe a Common Variable Immunodeficiency (CVI) patient with large
      granular (LG) lymphocytosis and systemic non-malignant lymphadenopathy who
      developed diffuse large B-cell lymphoma of the stomach. This is the first report
      of gastric high-grade lymphoma with widespread lymphadenopathy in a patient with
      LG lymphocytosis associated with CVI.

PMID- 17194668
TI  - Intractable myoclonus associated with anti-GluR3 antibodies after allogeneic bone
      marrow transplantation.

PMID- 17194669
TI  - Malaria and sickle cell disease.

PMID- 17194670
TI  - Helicobacter pylori and vitamin B12 deficiency.

PMID- 17194671
TI  - Cardiac determinants of survival in beta-thalassemia.

PMID- 17194672
TI  - Insulin resistance in children and adolescents after bone marrow transplantation
      for malignancies.

PMID- 17194674
TI  - Optimal post-remission therapy for flow-cytometry minimal residual disease
      positive adult patients with acute myeloid leukemia.

PMID- 17194675
TI  - Are women at higher risk than men? Gender differences among teenagers and adults
      in their response to threat of war and terror.
AB  - The present study examined whether women are at higher risk of developing stress
      reactions in situations of war and terror. The study looked at gender differences
      within two samples-teenagers (n = 353) and adults (n = 890)-regarding the impact
      of stress that developed in response to a situation of threat of war and terror
      as a result of Israel's withdrawal from Lebanon. The study tested: (1) gender
      differences regarding cognitive appraisal of the stressor, coping styles,
      psychological symptoms, and life satisfaction; (2) whether cognitive appraisal
      and coping styles mediated gender differences in psychological symptoms and life
      satisfaction; and (3) whether the two age groups differed regarding the
      contribution of gender to the studied variables. The results revealed that among
      the teenagers, gender differences were found only in cognitive appraisal and
      psychological symptoms, while among adults, gender differences were found in all
      the studied variables. The results support the mediating hypothesis with regard
      to psychological symptoms, but not with regard to life satisfaction. The results
      also show a different contribution of gender in each of the age groups regarding
      psychological symptoms, but not regarding life satisfaction, which leaves some
      doubt regarding the assumptions that women tend to be more affected by stress
      than men.

PMID- 17194676
TI  - Intimate partner violence and health provider training and screening in the news.
AB  - Intimate partner violence is a significant women's health issue. Since the news
      media can play a role in policy development, it is important to understand how
      newspapers have portrayed training and screening. The purpose of this study was
      to describe the frequency and nature of print news coverage of health issues
      related to partner violence, specifically, provider training and screening by
      health providers. We conducted a content analysis on articles obtained from major
      city and state capital daily newspapers from 20 states. News articles and
      editorials mentioning intimate partner violence and provider training and
      screening were examined for the years 1994 through 2001 (N = 188). Results showed
      that print news coverage was limited and received low levels of attention,
      indicating little potential to influence either policy or individual behavior.
      However, when the issue was covered, little debate or controversy was present,
      and a broad discussion of the issue was generally provided. News coverage of
      training and screening could be improved by increasing dissemination of research
      results, illustrating the policy implications of these issues, and offering
      resource information to women experiencing violence.

PMID- 17194677
TI  - Female veterans seeking medical care at Veterans Affairs primary care clinics:
      psychiatric and medical illness burden and service use.
AB  - OBJECTIVE: To examine rates of medical and psychiatric disorders among 187 female
      veterans recruited at four Veterans Affairs Medical Centers (VAMCs), the
      recognition of such disorders by VAMC care providers, and the use of relevant
      medical and mental health services by women both within and outside of the VA
      setting. METHODS: We used a cross-sectional, epidemiological design incorporating
      self-report measures, structured interviews, and chart reviews to obtain relevant
      information for analyses. RESULTS: Forty-four percent (43.9%) of women met
      criteria for at least one psychiatric disorder; 34.0% of these women met criteria
      for two or more additional psychiatric diagnoses, and concordance rates between
      interview and chart diagnoses were low. Ninety-five percent (95.2%) of women had
      a medical condition noted in their charts; 86.6% had two or more additional
      medical conditions, and a significant number of women had both medical and
      psychiatric diagnoses. Forty-four percent (43.9%) of women with an identified
      mental health condition received specialized mental health care by the VA in the
      past year. CONCLUSIONS: Findings from this study suggest that female veterans
      treated in VAMCs had significant medical and psychiatric problems, and these
      women might not be getting their health care needs adequately met through the VA
      health care system. In light of our findings, we discuss relevant implications
      and future directions for research.

PMID- 17194678
TI  - The meanings and experiences of cesarean birth among Cambodian, Lao and
      Vietnamese immigrant women in Australia.
AB  - We examined the experience of cesarean birth among 67 Cambodian, Lao and
      Vietnamese women who are now living in Melbourne, Australia, based on a larger
      ethnographic research project on childbearing, childrearing and motherhood among
      Southeast Asian women in Australia. We found a range of responses in the
      discourses of the women: some women preferred cesarean birth, but others resisted
      it. Women's social construction of their feelings stemmed from three interpretive
      frameworks: trust in medical knowledge, expectations (personal ideology of
      reproduction and motherhood) and communication with an understanding of their
      caregivers' preferences (as opposed to choice). Our findings have ramifications
      for health care providers working in multicultural settings. An effective
      dialogue between women and their health caregivers is required to keep the
      cesarean section rates down. In the case of immigrant women in a multicultural
      society like Australia, it is not the passive receipt of information but a two
      way communication with adequate interpreter support that will lead to informed
      choice, fewer cesarean births, more satisfaction and less regret.

PMID- 17194679
TI  - Comparing prenatal providers' approaches to four different risks: alcohol,
      tobacco, drugs, and domestic violence.
AB  - OBJECTIVE: We explored prenatal care providers' methods for addressing four
      behavioral risks in their pregnant patients: alcohol use, smoking, drug use, and
      domestic violence. DESIGN: We used qualitative, purposively sampled, focus group
      data. SETTING: Groups met in professional focus group settings. PARTICIPANTS: We
      conducted six focus groups (five with OB/Gyn physicians, one with nurse
      practitioners and certified nurse midwives), with a total of N = 49.
      MEASUREMENTS: The moderator used a focus group guide with open-ended questions,
      with probes where appropriate. FINDINGS: Providers' discussions reflected
      differences in how they approach each risk, including: (1) ambivalence about
      abstinence messages for alcohol; (2) relative comfort and confidence about
      assessing smoking and counseling to reduce smoking; (3) disparities across
      practice settings for toxicology screening for drugs; and (4) discomfort and
      pessimism with domestic violence. Investigators also analyzed providers'
      statements for each risk within the framework of the "Five A's" construct
      (Assess, Advise, Agree, Assist, and Arrange) for evaluating risk behavior
      interventions. CONCLUSIONS: A comparison of each risk across the Five A's
      illuminates the gaps between recommended and actual prevention methods and
      suggests directions for development of interventions and educational efforts.

PMID- 17194680
TI  - Women's perspectives on cervical screening and treatment in developing countries:
      experiences with new technologies and service delivery strategies.
AB  - This review of studies conducted by partners in the Alliance for Cervical Cancer
      Prevention (ACCP) examines women's perspectives on, and acceptability of, new
      cervical cancer screening and treatment approaches, management by mid-level
      staff, single-visit strategies, treatment side effects, and post-treatment
      abstinence requirements in low-resource settings. All screening, managed by
      female nurses and irrespective of method or constellation of methods, appeared to
      be highly acceptable. Similarly, cryotherapy treatment, including cryotherapy
      managed by nurses immediately after screening, was well-received by women in the
      studies. Minor side effects, although rather prevalent, and difficulties with
      post-treatment abstinence, did not appear to significantly deter women from
      recommending the procedure to friends. Rather, a sense of relief was evident, a
      feeling that it was better to be treated than not treated, and better to be
      treated sooner rather than later. While full replication may not be possible,
      this does not lessen the fact that screening and treatment in developing
      countries, even with new technologies, immediate treatment and even using mid
      level providers, can be very acceptable to women if provided in a safe, caring
      and preferably all-female environment.

PMID- 17194681
TI  - The interrelations between sexual orientation, sense of belonging and dysphoria
      among Australian women.
AB  - This research examined whether sense of belonging in the community and sexual
      orientation were associated with dysphoria among women. Australian female
      heterosexuals (n = 202) and lesbians (n = 184) completed the Sense of Belonging
      Instrument and the Depression, Anxiety, Stress Scales. Results indicated that
      lesbians experienced a decreased sense of belonging and more dysphoria compared
      with heterosexual women. Subsequent analyses indicated that sense of belonging to
      the community mediated the relation between sexual orientation and dysphoria. In
      addition, sexual orientation moderated the relation between sense of belonging
      and dysphoria. It appears that the enhancement of lesbians' sense of belonging in
      the community would be associated with a reduction in dysphoria.

PMID- 17194683
TI  - Hospital service recovery.
AB  - An organization's ability to correct service errors is an important factor in
      achieving success in today's service economy. This paper examines service
      recovery in hospitals in the U.S. First is a general review of service recovery
      theories. Next is a discussion of specific service issues related to the hospital
      environment. The literature on service recovery is used to make specific
      recommendations to hospitals for ways to improve their ability to remedy service
      errors when they occur. Suggestions for future research in the field of service
      recovery are also made.

PMID- 17194684
TI  - Global marketing of cholesterol-lowering drugs as therapy.
AB  - Pharmaceutical marketing services (PMS) are a key component of pharmaceutical
      companies' marketing strategies in that they create links between the
      pharmaceutical company and the physician. They are is also a link between
      physician and patients locally and globally. PMS discussed in this paper provide
      various services from tangible to intangible products in order to increase the
      physicians and pharmacists prescribing activities of their treatment modalities.
      Given the high cost of recruiting, training, and supporting PMS global marketing
      efforts, it is important for PMS channels to understand the significance of
      pharmaceutical multinational companies to ascribe to prescription drug services
      provided in Thailand. This created the unique marketing environment for the
      pharmaceutical companies. This study examines whether there is a gap in the
      existing cholesterol-lowering medication prescribed by physicians in Thailand and
      the newly introduced brand to the U.S. market. The degree of the new product
      adoption is analyzed through physician prescription frequency and records.
      Results of the study indicate there is significant improvement in the health
      conditions of the users of the new cholesterol medication among Thailand
      patients. Physicians in Thailand were, however, faced with competing brands in
      the market due to aggressiveness of advertising and promotion by multinational
      pharmaceutical marketing and manufacturers Associations. Perceived value and
      benefit to users were significant outcome of the study. More diagnostic and
      prescriptive research is recommended to cover Southeast Asia and other parts of
      the developing countries.

PMID- 17194685
TI  - Let's reach all of the market for health administration education: design,
      development, and delivery issues in distance delivery.
AB  - Web-based distance learning is an up and coming form of education. Web-based
      education delivered via a Web browser through the Internet has been found to be
      less expensive, more efficient, and sometimes more effective than classroom
      training. In the distance learning environment, the traditional "lecture and
      chalkboard" classroom pedagogy is completely absent. The virtual classroom
      becomes an "active learning" environment in which students, while utilizing
      technology, are able to discuss health administration concepts, analyze cases,
      work exercises, and discuss and share these interactively with both the
      instructor and fellow classmates. This method of Health Administration Education
      encourages students to learn from each other and promotes the open exchange of
      ideas and experiences. It does not require working students to put their careers
      on hold while they continue their studies. In this paper, we explore the
      opportunities and challenges of delivering web-based Health Administration
      courses via the Internet. Included is a discussion of the design, development,
      and delivery of a distance learning, web-based Health Administration Education
      system.

PMID- 17194686
TI  - A discussion of refractive medical behavior from an experiential marketing
      viewpoint.
AB  - Since the launch of National Health Insurance System, the financial source of
      funding for hospital financing has been reduced. Meanwhile, more and more
      customers attach importance to the experience of the medical process. Our study
      adopts "strategic modules of experiential marketing" by Schmitt to be the
      theoretical basis and proceed with in-depth interviews to discuss the influence
      of "medical behavior" on customers' experiences. We interviewed 32 patients who
      had a refractive surgery experience. The results show there are 10 propositions,
      which could be developed from 5 experiential modules - SENSE, FEEL, THINK, ACT,
      and RELATE - of customers' medical experiences. This study clarifies the
      experiences of customers during the process of a refractive surgery experience in
      order to provide medical institutions with the direction of experiential
      marketing to consider how to use experiential providers to reinforce customers'
      experiences.

PMID- 17194688
TI  - Exploring quality perceptions of health care operations: a study of public
      hospitals of Mauritius.
AB  - Patient care has become increasingly important in the health care environment of
      Mauritius. Patients' satisfaction and their expectations of health care are valid
      indicators of quality health care. The present paper reports the results of a
      survey of patient satisfaction with heath care, administered by face-to-face
      interview to 300 in-patient adults discharged from five main regional hospitals
      based in Mauritius. It examines the predictors and level of patients'
      satisfaction across the five regional hospitals of Mauritius. In this study, a
      modified version of HEALTHQUAL scale was used for determining patient
      satisfaction with health care in the regional public hospitals. Multiple
      regression analysis was conducted to understand the relationships among patients'
      perceptions of in-patient services and their overall perceptions of health care
      quality, and also satisfaction with their care and willingness to return or
      recommend the same hospital's services to others. The dimensions labelled as
      "Patients' perceptions of ward/hospital environment" and "Patients' perceptions
      of medical and nursing staff" served a significant impact on nearly all measures
      of patient satisfaction in the regional public hospitals of Mauritius.

PMID- 17194687
TI  - Medical informed consent: clarity or confusion?
AB  - Until the mid-twentieth century, rarely would a patient question a doctor's
      diagnosis or proposed treatment. The "good bedside manner" was used to describe a
      doctor who made the effort to explain medical procedures to his patients.
      Recently, however, the legal profession has begun questioning medical
      practitioners about treatments that have gone wrong. In this paper, the writers
      trace the concept of medical informed consent and explore whether the laws serve
      to protect and inform the public or whether they merely confuse the issues.

PMID- 17194689
TI  - Sales management coaching: a model for improved insurance company performance.
AB  - Of all the things sales managers do to develop salespeople, many people believe
      the most important one is coaching. Coaching is defined as using skills,
      experience, and direction to help someone improve their performance. Coaching
      consists primarily of giving people feedback to reinforce what they do well while
      suggesting ways and means to improve. Coaching implies that everybody can improve
      and hopefully everybody wants to get better at what they do. Many sales managers
      erroneously believe that they have to be better than the person they are coaching
      at the skill set they are discussing in order to be a useful coaching resource to
      that person. To be a good coach requires an understanding of the skills being
      discussed and a desire to help someone improve in the performance of their job.
      The sales manager who knows how to provide that feedback will have more
      productive, effective, satisfied, and motivated salespeople. This paper provides
      an overview of the coaching sequence and the skills required to make it work with
      some comment on how this was successfully applied to a major national insurance
      company. Sales Management styles vary, and what works for one person may not work
      for another. Effective Sales Management Coaching can provide sales managers with
      the skills to help salespeople grow and develop professionally.

PMID- 17194691
TI  - Mutations in fast skeletal troponin I, troponin T, and beta-tropomyosin that
      cause distal arthrogryposis all increase contractile function.
AB  - Distal arthrogryposes (DAs) are a group of disorders characterized by congenital
      contractures of distal limbs without overt neurological or muscle disease.
      Unexpectedly, mutations in genes encoding the fast skeletal muscle regulatory
      proteins troponin T (TnT), troponin I (TnI), and beta-tropomyosin (beta-TM) have
      been shown to cause autosomal dominant DA. We tested how these mutations affect
      contractile function by comparing wild-type (WT) and mutant proteins in
      actomyosin ATPase assays and in troponin-replaced rabbit psoas fibers. We have
      analyzed all four reported mutants: Arg63His TnT, Arg91Gly beta-TM, Arg174Gln
      TnI, and a TnI truncation mutant (Arg156ter). Thin filaments, reconstituted using
      actin and WT troponin and beta-TM, activated myosin subfragment-1 ATPase in a
      calcium-dependent, cooperative manner. Thin filaments containing either a
      troponin or beta-TM DA mutant produced significantly enhanced ATPase rates at all
      calcium concentrations without alternating calcium-sensitivity or cooperativity.
      In troponin-exchanged skinned fibers, each mutant caused a significant increase
      in Ca2+ sensitivity, and Arg156ter TnI generated significantly higher maximum
      force. Arg91Gly beta-TM was found to have a lower actin affinity than WT and form
      a less stable coiled coil. We propose the mutations cause increased contractility
      of developing fast-twitch skeletal muscles, thus causing muscle contractures and
      the development of the observed limb deformities.

PMID- 17194692
TI  - Diverse pathways for nuclear signaling by G protein-coupled receptors and their
      ligands.
AB  - Recent realization that plasma membrane G protein-coupled receptors (GPCRs) may
      translocate and establish ligand-responsive signaling complexes in other cellular
      structures has motivated studies of site-specific differences in transductional
      pathways. GPCRs and their ligands may signal transcription and other nuclear
      events by two basic mechanisms. The first consists of GPCR-complex activation of
      messengers that enter the nucleus and there initiate cell-modifying processes
      without the GPCR leaving the plasma membrane. The second encompasses entry into
      the nuclear membranes or matrix of either GPCR ligands, which bind to non-GPCR
      nuclear signaling proteins, proteolytic fragments of GPCRs capable of ligand
      independent signaling, or intact GPCRs with transduction-competent factors that
      directly initiate or regulate transcriptional events. With the second mechanism,
      often concurrent down-regulation of plasma membrane GPCRs terminates signaling
      from the cell-surface and moves it into the nuclear domain. Site-dependent
      differences in signals from the same GPCR provide potentials for unique cellular
      abnormalities attributable to defective intracellular movement and distribution
      of a GPCR, site-specific alterations in ligand concentration, and limited
      intracellular bioavailability of pharmacological agents that can interact
      specifically with both nuclear and plasma membrane forms of a GPCR.

PMID- 17194693
TI  - Consequences of expressing mutants of the hemochromatosis gene (HFE) into a human
      neuronal cell line lacking endogenous HFE.
AB  - HFE mutations have traditionally been associated with the iron overload disorder
      known as hemochromatosis. Recently, it has become clear that the two most common
      mutations in the HFE gene, H63D and C282Y, may be genetic modifiers for risk of
      neurodegenerative disorders and cancer, respectively. We developed human
      neuroblastoma stable cell lines that express either wild-type (WT) or mutant HFE
      to determine the cellular consequences of the mutant forms of HFE. The presence
      of the C282Y mutation was associated with relatively higher labile iron pool and
      iron regulatory protein activity than WT or H63D HFE. Targeted gene arrays
      revealed that the signal transduction pathway was up-regulated in the C282Y
      cells. H63D cells had higher levels of lipid peroxidation, protein oxidation, and
      lower mitochondrial membrane potential, suggesting higher baseline stress. This
      cell line was also more vulnerable to exposure to oxidative stress agents and
      more responsive to iron chelation than the C282Y cells. These data demonstrate
      that the different mutations in the HFE gene have unique effects on the cells and
      provide insights into how the different mutations may have different clinical
      consequences. The results also raise multiple novel questions for future study
      about the function of the HFE protein.

PMID- 17194694
TI  - Role of transport performance for neuron cell morphology.
AB  - The compartmental model is a basic tool for studying signal propagation in
      neurons; if the model parameters are adequately redefined, it can also be helpful
      in the study of electrical or fluid transport in other biological systems. Here
      we show that the input resistance in different networks that simulate the
      morphology of neurons is the result of the interplay between the relevant
      conductances, neuron morphology, and neuron size. The results suggest that
      neurons may grow in such a way that facilitates the current flow to the synapses,
      concurrently minimizing power consumption.

PMID- 17194695
TI  - LDL are oxidatively modified by platelets via GP91(phox) and accumulate in human
      monocytes.
AB  - Oxidative stress-mediated LDL modification has a key role in initiation of the
      atherosclerotic process. Platelets produce reactive oxidant species (ROS) upon
      stimulation with agonist, but it is uncertain whether they are able to
      oxidatively modify LDL. Human platelets taken from healthy subjects were
      incubated with LDL, then stimulated with collagen. Compared with unstimulated
      platelets, collagen-stimulated platelets induced LDL modification as shown by
      enhanced conjugated dienes and lysophosphatidylcholine formation, electrophoretic
      mobility, Apo B-100 degradation, and monocyte LDL uptake. Activated platelets
      also induced a marked reduction of vitamin E contained in LDL. A significant
      inhibition of LDL oxidation was observed in platelets treated with arachidonyl
      trifluomethyl ketone (AACOCF3), an inhibitor of phospholipase A2. The experiments
      reported above were also conducted in patients with hereditary deficiency of
      gp91phox, the central core of NADPH oxidase, and in patients with
      hypercholesterolemia. Platelets from gp91 phox-deficient patients produced a
      small amount of ROS and weakly modified LDL. Conversely, platelets from
      hypercholesterolemic patients showed enhanced ROS formation and oxidized LDL more
      than platelets from healthy subjects. This study provides evidence that platelets
      modify LDL via NADPH oxidase-mediated oxidative stress, a phenomenon that could
      be dependent on arachidonic acid activation. This finding suggests a role for
      platelets in favoring LDL accumulation within atherosclerotic plaque.

PMID- 17194696
TI  - Americans sweep Nobel Prizes: thinking inside and outside the box.

PMID- 17194697
TI  - DEA in consumer products is safe.

PMID- 17194700
TI  - Conditional activation of MET in differentiated skeletal muscle induces atrophy.
AB  - Skeletal muscle atrophy is a common debilitating feature of many systemic
      diseases, including cancer. Here we examined the effects of inducing expression
      of an oncogenic version of the Met receptor (Tpr-Met) in terminally
      differentiated skeletal muscle. A responder mouse containing the Tpr-Met oncogene
      and GFP (green fluorescent protein) as a reporter was crossed with a
      transactivator mouse expressing tTA under the control of the muscle creatine
      kinase promoter. Tpr-Met induction during fetal development and in young adult
      mice caused severe muscle wasting, with decreased fiber size and loss of myosin
      heavy chain protein. Concomitantly, in the Tpr-Met-expressing muscle the mRNA of
      the E3 ubiquitin ligases atrogin-1/MAFbx, MuRF1, and of the lysosomal protease
      cathepsin L, which are markers of skeletal muscle atrophy, was significantly
      increased. In the same muscles phosphorylation of the Met downstream effectors
      Akt, p38 MAPK, and IkappaBalpha was higher than in normal controls. Induction of
      Tpr-Met in differentiating satellite cells derived from the double transgenics
      caused aberrant cell fusion, protein loss, and myotube collapse. Increased
      phosphorylation of Met downstream effectors was also observed in the Tpr-Met
      expressing myotubes cultures. Treatment of these cultures with either a
      proteasomal or a p38 inhibitor prevented Tpr-Met-mediated myotube breakdown,
      establishing accelerated protein degradation consequent to inappropriate
      activation of p38 as the major route for the Tpr-Met-induced muscle phenotype.

PMID- 17194699
TI  - Angiotensin II inhibits the ROMK-like small conductance K channel in renal
      cortical collecting duct during dietary potassium restriction.
AB  - Base-line urinary potassium secretion in the distal nephron is mediated by small
      conductance rat outer medullary K (ROMK)-like channels. We used the patch clamp
      technique applied to split-open cortical collecting ducts (CCDs) isolated from
      rats fed a normal potassium (NK) or low potassium (LK) diet to test the
      hypothesis that AngII directly inhibits ROMK channel activity. We found that
      AngII inhibited ROMK channel activity in LK but not NK rats in a dose-dependent
      manner. The AngII-induced reduction in channel activity was mediated by AT1
      receptor (AT1R) binding, because pretreatment of CCDs with losartan but not
      PD123319 AT1 and AT2 receptor antagonists, respectively, blocked the response.
      Pretreatment of CCDs with U73122 and calphostin C, inhibitors of phospholipase C
      (PLC) and protein kinase C (PKC), respectively, abolished the AngII-induced
      decrease in ROMK channel activity, confirming a role of the PLC-PKC pathway in
      this response. Studies by others suggest that AngII stimulates an Src family
      protein-tyrosine kinase (PTK) via PKC-NADPH oxidase. PTK has been shown to
      regulate the ROMK channel. Inhibition of NADPH oxidase with diphenyliodonium
      abolished the inhibitory effect of AngII or the PKC activator phorbol 12
      myristate 13-acetate on ROMK channels. Suppression of PTK by herbimycin A
      significantly attenuated the inhibitory effect of AngII on ROMK channel activity.
      We conclude that AngII inhibits ROMK channel activity through PKC-, NADPH oxidase
      , and PTK-dependent pathways under conditions of dietary potassium restriction.

PMID- 17194701
TI  - Expression of constitutively active STAT3 can replicate the cytokine-suppressive
      activity of interleukin-10 in human primary macrophages.
AB  - There is general agreement that signal transducer and activation of transcription
      3 (STAT3) is required to mediate the anti-inflammatory activities of interleukin
      (IL)-10. However, STAT3 is activated by multiple factors that do not share the
      anti-inflammatory activity of IL-10. The question remains whether STAT3 is
      sufficient for the anti-inflammatory effects or whether there are other signals
      required, as had been suggested previously. We set out to map the human IL-10
      receptor and to identify the key elements involved in transducing the cytokine
      suppressive effects of IL-10. We were able to show an absolute requirement for
      both of the tyrosine residues found within the YXXQ-STAT3-docking site within the
      IL-10 receptor 1 and that no other signals appeared to be required. We used a
      constitutively active STAT3 to determine whether expression of this factor could
      suppress lipopolysaccharide-induced tumor necrosis factor and IL-6 production.
      Our data show that STAT3 activity can suppress both IL-6 and tumor necrosis
      factor production in lipopolysaccharide-stimulated macrophages. However, in
      synovial fibroblasts, STAT3 did not suppress IL-6 production, suggesting that the
      cellular environment plays an important role in dictating whether STAT3 drives a
      pro- or anti-inflammatory response.

PMID- 17194702
TI  - Myogenin and the SWI/SNF ATPase Brg1 maintain myogenic gene expression at
      different stages of skeletal myogenesis.
AB  - Many studies have examined transcriptional regulation during the initiation of
      skeletal muscle differentiation; however, there is less information regarding
      transcriptional control during adult myogenesis and during the maintenance of the
      differentiated state. MyoD and the mammalian SWI/SNF chromatin-remodeling enzymes
      containing the Brg1 ATPase are necessary to induce myogenesis in cell culture
      models and in developing embryonic tissue, whereas myogenin and Brg1 are critical
      for the expression of the late genes that induce terminal muscle differentiation.
      Here, we demonstrate that myogenin also binds to its own promoter during the late
      stages of embryonic muscle development. As is the case during embryonic
      myogenesis, MyoD and Brg1 co-localize to the myogenin promoter in primary adult
      muscle satellite cells. However, in mature myofibers, myogenin and Brg1 are
      preferentially co-localized to the myogenin promoter. Thus, the myogenin promoter
      is occupied by different myogenic factors at different times of myogenesis. The
      relevance of myogenin in the continued expression from its own promoter is
      demonstrated in culture, where we show that myogenin, in the absence of MyoD, is
      capable of maintaining its own expression by recruiting the Brg1 ATPase to modify
      promoter chromatin structure and facilitate myogenin expression. Finally, we
      utilized in vivo electroporation to demonstrate that Brg1 is required for the
      continued production of the myogenin protein in newborn skeletal muscle tissue.
      These findings strongly suggest that the skeletal muscle phenotype is maintained
      by myogenin and the continuous activity of Brg1-based SWI/SNF chromatin
      remodeling enzymes.

PMID- 17194704
TI  - Reversible hexacoordination of alpha-hemoglobin-stabilizing protein (AHSP)/alpha
      hemoglobin Versus pressure. Evidence for protection of the alpha-chains by their
      chaperone.
AB  - Using high hydrostatic pressure or hydrogen peroxide as perturbing agents, we
      demonstrate a protective effect of the chaperone AHSP for the alpha-chains of Hb.
      High pressure induces an irreversible aggregation of the ferrous deoxy alpha
      chains, whereas the AHSP/alpha-Hb complex shows reversible hexacoordination of
      the alpha-Hb without protein aggregation. Upon pressure release, the relaxation
      kinetics of the transition from the hexacoordinated to pentacoordinated form of
      alpha-Hb in the presence of AHSP exhibit a biphasic shape. High pressure did not
      induce dissociation of alpha-Hb from its chaperone, as evidenced by the ligand
      binding kinetics that show a unique rate for the AHSP/alpha-Hb complex. For both
      free alpha-Hb and the AHSP/alpha-Hb complex, the bimolecular rate constant of CO
      binding (k(CO)(on)) versus pressure exhibits a bell shape, attributed to the
      transition of the rate-determining step from the chemical barrier to the
      migration of CO within the protein matrix. These results reveal a plasticity of
      the alpha-Hb active site in the presence of the chaperone and indicate that the
      AHSP was still active at 300 MPa. The ferric state of the AHSP/alpha-Hb complex
      shows hexacoordination even at atmospheric pressures, indicating a His-Fe-His
      binding scheme as previously observed in neuroglobin and cytoglobin. The reaction
      with hydrogen peroxide of ferric alpha-Hb within the complex also demonstrates a
      protection against aggregation.

PMID- 17194705
TI  - 15-deoxyspergualin primarily targets the trafficking of apicoplast proteins in
      Plasmodium falciparum.
AB  - 15-Deoxyspergualin, an immunosuppressant with tumoricidal and antimalarial
      properties, has been implicated in the inhibition of a diverse array of cellular
      processes including polyamine synthesis and protein synthesis. Endeavoring to
      identify the mechanism of antimalarial action of this molecule, we examined its
      effect on Plasmodium falciparum protein synthesis, polyamine biosynthesis, and
      transport. 15-Deoxyspergualin stalled protein synthesis in P. falciparum through
      Hsp70 sequestration and subsequent phosphorylation of the eukaryotic initiation
      factor eIF2alpha. However, protein synthesis inhibition as well as polyamine
      depletion were invoked only by high micromolar concentrations of 15
      deoxyspergualin, in contrast to the submicromolar concentrations sufficient to
      inhibit parasite growth. Further investigations demonstrated that 15
      deoxyspergualin in the malaria parasite primarily targets the hitherto
      underexplored process of trafficking of nucleus-encoded proteins to the
      apicoplast. Our finding that 15-deoxyspergualin kills the malaria parasite by
      interfering with targeting of nucleus-encoded proteins to the apicoplast not only
      exposes a chink in the armor of the malaria parasite, but also reveals new realms
      in our endeavors to study this intriguing biological process.

PMID- 17194703
TI  - Chlamydomonas flagellar outer row dynein assembly protein ODA7 interacts with
      both outer row and I1 inner row dyneins.
AB  - We previously found that a mutation at the ODA7 locus in Chlamydomonas prevents
      axonemal outer row dynein assembly by blocking association of heavy chains and
      intermediate chains in the cytoplasm. We have now cloned the ODA7 locus by
      walking in the Chlamydomonas genome from nearby molecular markers, confirmed the
      identity of the gene by rescuing the mutant phenotype with genomic clones, and
      identified the ODA7 gene product as a 58-kDa leucine-rich repeat protein
      unrelated to outer row dynein LC1. Oda7p is missing from oda7 mutant flagella but
      is present in flagella of other outer row or inner row dynein assembly mutants.
      However, Oda7 levels are greatly reduced in flagella that lack both outer row
      dynein and inner row I1 dynein. Biochemical fractionation and rebinding studies
      support a model in which Oda7 participates in a previously uncharacterized
      structural link between inner and outer row dyneins.

PMID- 17194706
TI  - Molecular properties of rhodopsin and rod function.
AB  - Signal transduction in rod cells begins with photon absorption by rhodopsin and
      leads to the generation of an electrical response. The response profile is
      determined by the molecular properties of the phototransduction components. To
      examine how the molecular properties of rhodopsin correlate with the rod-response
      profile, we have generated a knock-in mouse with rhodopsin replaced by its E122Q
      mutant, which exhibits properties different from those of wild-type (WT)
      rhodopsin. Knock-in mouse rods with E122Q rhodopsin exhibited a photosensitivity
      about 70% of WT. Correspondingly, their single-photon response had an amplitude
      about 80% of WT, and a rate of decline from peak about 1.3 times of WT. The
      overall 30% lower photosensitivity of mutant rods can be explained by a lower
      pigment photosensitivity (0.9) and the smaller single-photon response (0.8). The
      slower decline of the response, however, did not correlate with the 10-fold
      shorter lifetime of the meta-II state of E122Q rhodopsin. This shorter lifetime
      became evident in the recovery phase of rod cells only when arrestin was absent.
      Simulation analysis of the photoresponse profile indicated that the slower
      decline and the smaller amplitude of the single-photon response can both be
      explained by the shift in the meta-I/meta-II equilibrium of E122Q rhodopsin
      toward meta-I. The difference in meta-III lifetime between WT and E122Q mutant
      became obvious in the recovery phase of the dark current after moderate
      photobleaching of rod cells. Thus, the present study clearly reveals how the
      molecular properties of rhodopsin affect the amplitude, shape, and kinetics of
      the rod response.

PMID- 17194708
TI  - Organismal differences in post-translational modifications in histones H3 and H4.
AB  - Post-translational modifications (PTMs) of histones play an important role in
      many cellular processes, notably gene regulation. Using a combination of mass
      spectrometric and immunobiochemical approaches, we show that the PTM profile of
      histone H3 differs significantly among the various model organisms examined.
      Unicellular eukaryotes, such as Saccharomyces cerevisiae (yeast) and Tetrahymena
      thermophila (Tet), for example, contain more activation than silencing marks as
      compared with mammalian cells (mouse and human), which are generally enriched in
      PTMs more often associated with gene silencing. Close examination reveals that
      many of the better-known modified lysines (Lys) can be either methylated or
      acetylated and that the overall modification patterns become more complex from
      unicellular eukaryotes to mammals. Additionally, novel species-specific H3 PTMs
      from wild-type asynchronously grown cells are also detected by mass spectrometry.
      Our results suggest that some PTMs are more conserved than previously thought,
      including H3K9me1 and H4K20me2 in yeast and H3K27me1, -me2, and -me3 in Tet. On
      histone H4, methylation at Lys-20 showed a similar pattern as H3 methylation at
      Lys-9, with mammals containing more methylation than the unicellular organisms.
      Additionally, modification profiles of H4 acetylation were very similar among the
      organisms examined.

PMID- 17194707
TI  - XT-II, the second isoform of human peptide-O-xylosyltransferase, displays
      enzymatic activity.
AB  - Peptide O-xylosyltransferase (EC 2.4.2.26) is the first enzyme required for the
      generation of chondroitin and heparan sulfate glycosaminoglycan chains of
      proteoglycans. Cloning of cDNAs has previously shown that, whereas invertebrates
      generally have a single xylosyltransferase gene, vertebrate genomes encode two
      similar proteins, xylosyltransferase I and II (XT-I and XT-II). To date,
      enzymatic activity has only been demonstrated for the human XT-I, Caenorhabditis
      SQV-6, and Drosophila OXT isoforms. In the present study, we demonstrate that a
      soluble form of human XT-II expressed in the xylosyltransferase-deficient pgsA
      745 (S745) Chinese hamster ovary cell line is indeed capable of catalyzing the
      transfer of xylose to a variety of peptide substrates; its enzyme activity was
      also proven using a Pichia-expressed form of XT-II. Its pH, temperature, and
      cation dependences are similar to those of XT-I expressed in either mammalian
      cells or yeast. Our data suggest that XT-I and XT-II are, at least in vitro,
      functionally identical.

PMID- 17194709
TI  - Two novel members of the ABLIM protein family, ABLIM-2 and -3, associate with
      STARS and directly bind F-actin.
AB  - In addition to regulating cell motility, contractility, and cytokinesis, the
      actin cytoskeleton plays a critical role in the regulation of transcription and
      gene expression. We have previously identified a novel muscle-specific actin
      binding protein, STARS (striated muscle activator of Rho signaling), which
      directly binds actin and stimulates serum-response factor (SRF)-dependent
      transcription. To further dissect the STARS/SRF pathway, we performed a yeast two
      hybrid screen of a skeletal muscle cDNA library using STARS as bait, and we
      identified two novel members of the ABLIM protein family, ABLIM-2 and -3, as
      STARS-interacting proteins. ABLIM-1, which is expressed in retina, brain, and
      muscle tissue, has been postulated to function as a tumor suppressor. ABLIM-2 and
      -3 display distinct tissue-specific expression patterns with the highest
      expression levels in muscle and neuronal tissue. Moreover, these novel ABLIM
      proteins strongly bind F-actin, are localized to actin stress fibers, and
      synergistically enhance STARS-dependent activation of SRF. Conversely, knockdown
      of endogenous ABLIM expression utilizing small interfering RNA significantly
      blunted SRF-dependent transcription in C2C12 skeletal muscle cells. These
      findings suggest that the members of the novel ABLIM protein family may serve as
      a scaffold for signaling modules of the actin cytoskeleton and thereby modulate
      transcription.

PMID- 17194710
TI  - Gender differences in the consumption of meat, fruit and vegetables are similar
      in Finland and the Baltic countries.
AB  - BACKGROUND: Women's diets are healthier than men's. Finnish women eat more fruits
      and vegetables but less meat than men. Gender differences may be larger in the
      Baltic countries, which represent Eastern European transition societies than in
      Finland, a society characterized by the Scandinavian welfare ideology and a high
      degree of gender equality. METHODS: The data are based on questionnaires to
      random samples of adults in Finland, Estonia, Latvia and Lithuania. The data
      provide a way of addressing gender differences at the turn of the century in the
      economically and culturally different countries. The purpose is to explore
      whether the consumption of foods classified as masculine or feminine-meat, fruits
      and vegetables-follow a similar gender pattern in Finland and the Baltic
      countries. RESULTS: Men ate meat more often while women ate fruits and
      vegetables. A high educational level was associated with frequent consumption of
      fruits and vegetables. Educational differences in the consumption of meat were
      few and inconsistent. The consumption of fruits and vegetables was more common in
      urban areas except in Finland. Gender differences were similar in all countries
      throughout age and educational groups and in rural and urban areas. CONCLUSION:
      The consistent association of gender and food and the similarity of gender
      patterning in population subgroups point to the stability of masculine versus
      feminine food habits. The similarity suggests that food habits contribute equally
      to the gender gap in health in the Baltic countries as they do in Finland.

PMID- 17194711
TI  - Target lesion revascularisation in patients treated with a sirolimus-eluting or
      paclitaxel-eluting stent.
AB  - OBJECTIVE: To identify risk factors for clinical-driven target lesion
      revascularisation (TLR) in patients treated with sirolimus-eluting (Cypher) or
      paclitaxel-eluting (Taxus) stents in a real-world scenario. DESIGN: From 1
      January 2003 to 18 May 2005, all patients treated with a Cypher or Taxus stent
      were consecutively registered and followed for 9 months. Re-intervention was
      driven by clinical symptoms. SETTING: Western Denmark Heart Registry. PATIENTS:
      4432 patients with 6102 lesions treated with a Cypher (n = 3791 lesions) or Taxus
      (n = 2311 lesions) stent. INTERVENTIONS: Percutaneous coronary intervention. MAIN
      OUTCOME MEASURES: TLR, defined as either new percutaneous coronary intervention
      or coronary artery bypass graft operation of the target lesion, within 9 months
      from the index procedure. RESULTS: TLR within 9 months was performed in 2.5% of
      lesions treated with the Cypher stent and in 3.3% of lesions treated with the
      Taxus stent (OR 1.36, 95% CI 1.00 to 1.84). After adjustment by multivariate
      logistic regression, Taxus stent implantation was an independent predictor of TLR
      (OR 1.43, 95% CI 1.05 to 1.95). Implantation of >1 stent per lesion (OR 1.62, 95%
      CI 1.13 to 2.33) and reference diameter <2.8 mm (OR 1.42, 95% CI 1.00 to 2.02)
      were also identified as independent predictors of TLR. CONCLUSIONS: These data
      from the registry reflect a real-world clinical scenario with operator-driven use
      of drug-eluting stents and symptom-driven re-intervention. In this setting, use
      of the Taxus stent, implantation of multiple stents per lesion and stent
      implantation in small vessels were independent predictors of TLR.

PMID- 17194712
TI  - Myeloperoxidase aids prognostication together with N-terminal pro-B-type
      natriuretic peptide in high-risk patients with acute ST elevation myocardial
      infarction.
AB  - BACKGROUND: Inflammation plays a critical role in acute myocardial infarction
      (MI). One such inflammatory marker is myeloperoxidase (MPO). Its role as a
      predictor of death or MI in patients with ST segment elevation myocardial
      infarction (STEMI) is unclear. AIM: To investigate the role of MPO as a predictor
      of death or MI in patients with STEMI and to compare it with N-terminal pro-B
      type natriuretic peptide (NT-BNP). METHOD: 384 post STEMI patients were studied.
      Patients were followed up for the combined end point of death or readmission with
      non-fatal MI. RESULTS: There were 40 deaths and 37 readmissions with MI. Median
      MPO was raised in patients experiencing death or MI than in survivors (median
      (range), 50.6 (15.3-124.1) ng/ml vs 33.5 (6.6-400.2) ng/ml, p = 0.001). Using a
      Cox proportional hazards model, log median MPO (HR 6.91, 95% CI 1.79 to 26.73, p
      = 0.005) and log median NT-BNP (HR 4.21, 95% CI 1.53 to 11.58, p = 0.005)
      independently predicted death or non-fatal MI. MPO had predictive power in both
      below and above median NT-BNP levels (log rank 5.60, p = 0.020 and log rank 5.12,
      p = 0.024, respectively). The receiver-operating curve for median NT-BNP yielded
      an area under the curve (AUC) of 0.72 (95% CI 0.65 to 0.79, p<0.001); for median
      MPO, the AUC was 0.62 (95% CI 0.55 to 0.69, p = 0.001). The logistic model
      combining the two markers yielded an AUC of 0.76 (95% CI 0.69 to 0.82, p<0.001).
      CONCLUSION: MPO and NT-BNP may be useful tools for risk stratification of all
      acute coronary syndromes, including patients with STEMI at higher risk.

PMID- 17194714
TI  - On hobgoblins and consistency.

PMID- 17194713
TI  - Circulating endothelial progenitor cells in patients with cardiac syndrome X.
AB  - BACKGROUND: Cardiac syndrome X (CSX) encompasses the constellation of anginal
      chest pain in the presence of a pathological functional test and a normal
      coronary angiogram. Endothelial progenitor cells (EPCs) in the peripheral
      circulation contribute to tissue vascularisation. OBJECTIVE: To investigate the
      number and functional properties of circulating EPCs in patients with CSX.
      METHODS: 17 patients with CSX and a referent population (n = 20) were matched for
      age, atherosclerotic risk factors and use of drugs. Numbers of EPCs were studied
      by FACS, and their functional properties, including their proliferative capacity,
      adherence to matrix and mature endothelial cells as well as their ability to
      support in vitro tube formation, were investigated. Levels of soluble markers
      that associate with peripheral mobilisation and homing were studied in the serum
      samples of all subjects. RESULTS: Patients with CSX had significantly increased
      numbers of circulating EPCs as compared with the referent population (both
      CD34+/KDR and CD34+/CD133+). The proliferative capacity of EPCs and their ability
      to support in vitro tube formation were significantly impaired in patients with
      CSX as compared with the referent population. However, adhesiveness of EPCs from
      patients with CSX to fibronectin and cultured mature endothelial cells was
      enhanced as compared with the referent population. Serum vascular endothelial
      growth factor correlated with peripheral CD34+/KDR cell numbers, whereas serum
      concentration of erythropoietin correlated with the number of circulating
      CD34+/CD133+ cells CONCLUSION: Patients with CSX have a significantly altered
      circulating EPC phenotype that could potentially aid in understanding the complex
      pathogenesis of the syndrome.

PMID- 17194716
TI  - Three-dimensional quantitative structure-activity relationship analysis of human
      CYP51 inhibitors.
AB  - CYP51 fulfills an essential requirement for all cells, by catalyzing three
      sequential mono-oxidations within the cholesterol biosynthesis cascade.
      Inhibition of fungal CYP51 is used as a therapy for treating fungal infections,
      whereas inhibition of human CYP51 has been considered as a pharmacological
      approach to treat dyslipidemia and some forms of cancer. To predict the
      interaction of inhibitors with the active site of human CYP51, a three
      dimensional quantitative structure-activity relationship model was constructed.
      This pharmacophore model of the common structural features of CYP51 inhibitors
      was built using the program Catalyst from multiple inhibitors (n = 26) of
      recombinant human CYP51-mediated lanosterol 14alpha-demethylation. The
      pharmacophore, which consisted of one hydrophobe, one hydrogen bond acceptor, and
      two ring aromatic features, demonstrated a high correlation between observed and
      predicted IC(50) values (r = 0.92). Validation of this pharmacophore was
      performed by predicting the IC(50) of a test set of commercially available (n =
      19) and CP-320626-related (n = 48) CYP51 inhibitors. Using predictions below 10
      microM as a cutoff indicative of active inhibitors, 16 of 19 commercially
      available inhibitors (84%) and 38 of 48 CP-320626-related inhibitors (79.2%) were
      predicted correctly. To better understand how inhibitors fit into the enzyme,
      potent CYP51 inhibitors were used to build a Cerius(2) receptor surface model
      representing the volume of the active site. This study has demonstrated the
      potential for ligand-based computational pharmacophore modeling of human CYP51
      and enables a high-throughput screening system for drug discovery and data base
      mining.

PMID- 17194715
TI  - CAR2 displays unique ligand binding and RXRalpha heterodimerization
      characteristics.
AB  - The constitutive androstane receptor (CAR; NR1I3) regulates the expression of
      genes involved in xenobiotic metabolism. Alternative splicing of the human CAR
      gene yields an array of mRNAs that encode structurally diverse proteins. One form
      of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are
      predicted to reshape the ligand-binding pocket. The current studies show a
      marked, ligand-independent, CAR2-mediated transactivation of reporters containing
      optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the
      natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand
      binding domain was critical for achieving these effects. CAR2 interaction with
      SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of
      Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher
      constitutive activity. Alternatively, mutating Ser233 to an aspartate residue
      drastically reduced the transactivation capacity of CAR2. The respective
      abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter
      element correlated with their ability to interact with RxRalpha and to recruit
      SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust
      RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In
      addition, CAR2 displays novel dose responses to clotrimazole and androstanol
      compared with the reference form of the receptor while at the same time retaining
      the ability to bind CITCO. This result supports a hypothesis whereby the four
      amino-acid insertion in CAR2 structurally modifies its ligand binding pocket,
      suggesting that CAR2 is regulated by a set of ligands distinct from those
      governing the activity of reference CAR.

PMID- 17194717
TI  - In vitro and in vivo determination of piperacillin metabolism in humans.
AB  - Piperacillin metabolism and biliary excretion are different between humans and
      preclinical species. In the present study, piperacillin metabolites were
      characterized in bile and urine of healthy humans and compared with metabolites
      formed in vitro. Volunteers were administered 2 g of piperacillin IV; blood,
      urine, and duodenal aspirates (obtained via a custom-made oroenteric catheter)
      were collected. The metabolism of piperacillin in humans also was investigated in
      vitro using pooled human liver microsomes and sandwich-cultured human
      hepatocytes. Piperacillin and metabolites were estimated by high-performance
      liquid chromatography with tandem mass spectrometry detection. Piperacillin,
      desethylpiperacillin, and desethylpiperacillin glucuronide were detected in bile,
      urine, and human liver microsomal incubates. Similar to the in vivo results,
      desethylpiperacillin was formed and excreted into bile canaliculi of sandwich
      cultured human hepatocytes. This is the first report of glucuronidation of
      desethylpiperacillin in vitro or in vivo. The clinical method employed in this
      study to determine biliary clearance of drugs also facilitates bile collection as
      soon as bile is excreted from the gallbladder, thereby minimizing the exposure of
      labile metabolites to the intestinal environment. This study exemplifies how a
      combination of in vitro and in vivo tools can aid in the identification of
      metabolites unique to the human species.

PMID- 17194718
TI  - A deficient TLR2 signaling promotes airway mucin production in Mycoplasma
      pneumoniae-infected allergic mice.
AB  - The original hygiene hypothesis suggests that early childhood respiratory
      infections preceding allergen exposure may decrease the prevalence of allergic
      diseases. We have recently demonstrated that Mycoplasma pneumoniae infection
      preceding allergen exposure reduced allergic responses in mice. However, the
      molecular mechanisms underlying the protective role of M. pneumoniae in allergic
      responses, particularly airway mucin production, remain unclear. Wild-type and
      Toll-like receptor 2 (TLR2)-deficient mice with a respiratory M. pneumoniae
      infection preceding allergen (ovalbumin) challenge were utilized to determine the
      regulatory role of TLR2-IFN-gamma signaling pathway in airway mucin expression.
      Furthermore, air-liquid interface cultures of mouse primary tracheal epithelial
      cells were performed to examine the effects of IFN-gamma on mucin expression. In
      wild-type mice, M. pneumoniae infection preceding allergen challenge
      significantly reduced airway mucins but increased IFN-gamma. In sharp contrast,
      in TLR2-deficient mice, M. pneumoniae preceding allergen challenge resulted in
      increased mucin protein without a noticeable change of IFN-gamma. In cultured
      mouse primary tracheal epithelial cells, IFN-gamma was shown to directly inhibit
      mucin expression in a dose-dependent manner. Our study demonstrates for the first
      time that a respiratory M. pneumoniae infection preceding allergen challenge
      reduces airway epithelial mucin expression in part through TLR2-IFN-gamma
      signaling pathway. A bacterial infection in asthmatic subjects with weakened TLR2
      IFN-gamma signaling may result in an exaggerated airway mucin production.

PMID- 17194719
TI  - NMR structure of stem-loop D from human rhinovirus-14.
AB  - The 5'-cloverleaf of the picornavirus RNA genome is essential for the assembly of
      a ribonucleoprotein replication complex. Stem-loop D (SLD) of the cloverleaf is
      the recognition site for the multifunctional viral protein 3Cpro. This protein is
      the principal viral protease, and its interaction with SLD also helps to position
      the viral RNA-dependent RNA polymerase (3Dpol) for replication. Human rhinovirus
      14 (HRV-14) is distinct from the majority of picornaviruses in that its SLD forms
      a cUAUg triloop instead of the more common uYACGg tetraloop. This difference
      appears to be functionally significant, as 3Cpro from tetraloop-containing
      viruses cannot bind the HRV-14 SLD. We have determined the solution structure of
      the HRV-14 SLD using NMR spectroscopy. The structure is predominantly an A-form
      helix, but with a central pyrimidine-pyrimidine base-paired region and a
      significantly widened major groove. The stabilizing hydrogen bonding present in
      the uYACGg tetraloop was not found in the cUAUg triloop. However, the triloop
      uses different structural elements to present a largely similar surface: sequence
      and underlying architecture are not conserved, but key aspects of the surface
      structure are. Important structural differences do exist, though, and may account
      for the observed cross-isotype binding specificities between 3Cpro and SLD.

PMID- 17194720
TI  - Mass spectrometry-based detection of transfer RNAs by their signature
      endonuclease digestion products.
AB  - The separation of biologically active, pure, and specific tRNAs is difficult due
      to the overall similarity in secondary and tertiary structures of different
      tRNAs. Because prior methods do not facilitate high-resolution separations of the
      extremely complex mixture represented by a cellular tRNA population, global
      studies of tRNA identity and/or abundance are difficult. We have discovered that
      the enzymatic digestion of an individual tRNA by a ribonuclease (e.g., RNase T1)
      will generate digestion products unique to that particular tRNA, and we show that
      a comparison of an organism's complete complement of tRNA RNase digestion
      products yields a set of unique or "signature" digestion product(s) that
      ultimately enable the detection of individual tRNAs from a total tRNA pool.
      Detection is facilitated by matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) and proof-of-principle is demonstrated on the whole tRNA
      pool from Escherichia coli. This method will enable the individual identification
      of tRNA isoacceptors without requiring specific affinity purification or
      extensive chromatographic and/or electrophoretic purification. Further,
      experimental identifications of tRNAs or other RNAs will now be possible using
      this signature digestion product approach in a manner similar to peptide mass
      fingerprinting used in proteomics, allowing RNomic studies of RNA at the post
      transcriptional level.

PMID- 17194723
TI  - Physiologically high concentrations of 17beta-estradiol enhance NF-kappaB
      activity in human T cells.
AB  - Estrogen has diverse effects on inflammation and immune responses. That pregnancy
      is associated with remission of some autoimmune diseases and exacerbation of
      others suggests that physiological fluctuation in estrogen levels could affect
      the immune responses in humans. However, the molecular basis for these phenomena
      is poorly understood. We hypothesized that fluctuations of estrogen levels
      modulate intracellular signaling for immune responses via estrogen receptors
      (ERs). In reporter assays, 17beta-estradiol (E2) at a physiologically high
      concentration increased the activity of NF-kappaB in Jurkat cells stimulated by
      PMA/ionomycin or TNF-alpha. Overexpression and RNA interference experiments
      suggested that the effects were mediated through ERbeta. Immunoprecipitation
      assay showed that both ERalpha and ERbeta are directly associated with NF-kappaB
      in the cell nucleus. Using chromatin immunoprecipitation assay, we confirmed that
      ERalpha and ERbeta associated with NF-kappaB and steroid hormone coactivators at
      the promoter region of NF-kappaB regulated gene. Considering that NF-kappaB
      regulates the expression of various genes essential for cell growth and death,
      estrogen could regulate the fate of T cells by affecting the activity of NF
      kappaB. To determine whether E2 alters the fate of T cells, we investigated E2
      actions on T cell apoptosis, a well-known NF-kappaB-mediated phenomenon. E2
      increased apoptosis of Jurkat cells and decreased that of human peripheral blood
      T cells. Our results indicate that E2 at a physiologically high concentration
      modulates NF-kappaB signaling in human T cells via ERbeta and affects T cell
      survival, suggesting that these actions may underlie the gender differences in
      autoimmune diseases.

PMID- 17194721
TI  - Structural plasticity and Mg2+ binding properties of RNase P P4 from combined
      analysis of NMR residual dipolar couplings and motionally decoupled spin
      relaxation.
AB  - The P4 helix is an essential element of ribonuclease P (RNase P) that is believed
      to bind catalytically important metals. Here, we applied a combination of NMR
      residual dipolar couplings (RDCs) and a recently introduced domain-elongation
      strategy for measuring "motionally decoupled" relaxation data to characterize the
      structural dynamics of the P4 helix from Bacillus subtilis RNase P. In the
      absence of divalent ions, the two P4 helical domains undergo small amplitude
      (approximately 13 degrees) collective motions about an average interhelical angle
      of 10 degrees. The highly conserved U7 bulge and helical residue C8, which are
      proposed to be important for substrate recognition and metal binding, are locally
      mobile at pico- to nanosecond timescales and together form the pivot point for
      the collective domain motions. Chemical shift mapping reveals significant
      association of Mg2+ ions at the P4 major groove near the flexible pivot point at
      residues (A5, G22, G23) previously identified to bind catalytically important
      metals. The Mg2+ ions do not, however, significantly alter the structure or
      dynamics of P4. Analysis of results in the context of available X-ray structures
      of the RNA component of RNase P and structural models that include the pre-tRNA
      substrate suggest that the internal motions observed in P4 likely facilitate
      adaptive changes in conformation that take place during folding and substrate
      recognition, possibly aided by interactions with Mg2+ ions. Our results add to a
      growing view supporting the existence of functionally important internal motions
      in RNA occurring at nanosecond timescales.

PMID- 17194722
TI  - Unique folding of precursor microRNAs: quantitative evidence and implications for
      de novo identification.
AB  - MicroRNAs (miRNAs) participate in diverse cellular and physiological processes
      through the post-transcriptional gene regulatory pathway. Hairpin is a crucial
      structural feature for the computational identification of precursor miRNAs (pre
      miRs), as its formation is critically associated with the early stages of the
      mature miRNA biogenesis. Our incomplete knowledge about the number of miRNAs
      present in the genomes of vertebrates, worms, plants, and even viruses
      necessitates thorough understanding of their sequence motifs, hairpin structural
      characteristics, and topological descriptors. In this in-depth study, we
      investigate a comprehensive and heterogeneous collection of 2241 published
      (nonredundant) pre-miRs across 41 species (miRBase 8.2), 8494 pseudohairpins
      extracted from the human RefSeq genes, 12,387 (nonredundant) ncRNAs spanning 457
      types (Rfam 7.0), 31 full-length mRNAs randomly selected from GenBank, and four
      sets of synthetically generated genomic background corresponding to each of the
      native RNA sequence. Our large-scale characterization analysis reveals that pre
      miRs are significantly different from other types of ncRNAs, pseudohairpins,
      mRNAs, and genomic background according to the nonparametric Kruskal-Wallis ANOVA
      (p<0.001). We examine the intrinsic and global features at the sequence,
      structural, and topological levels including %G+C content, normalized base
      pairing propensity P(S), normalized minimum free energy of folding MFE(s),
      normalized Shannon entropy Q(s), normalized base-pair distance D(s), and degree
      of compactness F(S), as well as their corresponding Z scores of P(S), MFE(s),
      Q(s), D(s), and F(S). The findings will promote more accurate guidelines and
      distinctive criteria for the prediction of novel pre-miRs with improved
      performance.

PMID- 17194724
TI  - Enhanced pelvic responses to stressors in female CRF-overexpressing mice.
AB  - Acute stress affects gut functions through the activation of corticotropin
      releasing factor (CRF) receptors. The impact of acute stress on pelvic viscera in
      the context of chronic stress is not well characterized. We investigated the
      colonic, urinary, and locomotor responses monitored as fecal pellet output (FPO),
      urine voiding, and ambulatory activity, respectively, in female and male CRF
      overexpressing (CRF-OE) mice, a chronic stress model, and their wild-type
      littermates (WTL). Female CRF-OE mice, compared with WTL, had enhanced FPO to 2
      min handling (150%) and 60-min novel environment (155%) but displayed a similar
      response to a 60-min partial restraint stress. Female CRF-OE mice, compared with
      WTL, also had a significantly increased number of urine spots (7.3 +/- 1.4 vs.
      1.3 +/- 0.8 spots/h) and lower locomotor activity (246.8 +/- 47.8 vs. 388.2 +/-
      31.9 entries/h) to a novel environment. Male CRF-OE mice and WTL both responded
      to a novel environment but failed to show differences between them in colonic and
      locomotor responses. Male WTL, compared with female WTL, had higher FPO (113%).
      In female CRF-OE mice, the CRF(1)/CRF(2) receptor antagonist astressin B and the
      selective CRF(2) receptor agonist mouse urocortin 2 (injected peripherally)
      prevented the enhanced defecation without affecting urine or locomotor responses
      to novel environment. RT-PCR showed that CRF(1) and CRF(2) receptors are
      expressed in the mouse colonic tissues. The data show that chronic stress, due to
      continuous central CRF overdrive, renders female CRF-OE mice to have enhanced
      pelvic and altered behavioral responses to superimposed mild stressors and that
      CRF(1)-initiated colonic response is counteracted by selective activation of
      CRF(2) receptor.

PMID- 17194725
TI  - HO-1 induction lowers blood pressure and superoxide production in the renal
      medulla of angiotensin II hypertensive mice.
AB  - Heme oxygenase-1 (HO-1) induction can attenuate the development of angiotensin II
      (ANG II)-dependent hypertension. However, the mechanism by which HO-1 lowers
      blood pressure in this model is not clear. The goal of this study was to test the
      hypothesis that induction of HO-1 in the kidney can attenuate the increase in
      reactive oxygen species (ROS) generation in the kidney that occurs during ANG II
      dependent hypertension. Mice were divided into four groups, control (Con), cobalt
      protoporphyrin (CoPP), ANG II, and ANG II + CoPP. CoPP treatment (50 mg/kg) was
      administered in a single subcutaneous injection 2 days prior to implantation of
      an osmotic minipump that infused ANG II at a rate of 1 microg x kg(-1) x min(-1).
      At the end of this period, mean arterial blood pressure (MAP) averaged 93 +/- 5,
      90 +/- 5, 146 +/- 8, and 105 +/- 6 mmHg in Con, CoPP-, ANG II-, and ANG II + CoPP
      treated mice. To determine whether HO-1 induction resulted in a decrease in ANG
      II-stimulated ROS generation in the renal medulla, superoxide production was
      measured. Medullary superoxide production was increased by ANG II infusion and
      normalized in mice pretreated with CoPP. The reduction in ANG II-mediated
      superoxide production in the medulla with CoPP was associated with a decrease in
      extracellular superoxide dismutase protein but an increase in catalase protein
      and activity. These results suggest that reduction in superoxide and possibly
      hydrogen peroxide production in the renal medulla may be a potential mechanism by
      which induction of HO-1 with CoPP lowers blood pressure in ANG-II dependent
      hypertension.

PMID- 17194726
TI  - Differential effects of intravenous hyperosmotic solutes on drinking latency and
      c-Fos expression in the circumventricular organs and hypothalamus of the rat.
AB  - Hyperosmotic intravenous infusions of NaCl are more potent for inducing drinking
      and vasopressin (AVP) secretion than equally osmotic solutions of glucose or
      urea. The fact that all three solutes increased cerebrospinal fluid osmolality
      and sodium concentration led the investigators to conclude that critical sodium
      receptors or osmoreceptors for stimulating drinking and AVP secretion were
      outside the blood-brain barrier (BBB) in the circumventricular organs (CVOs). We
      tested an obvious prediction of this hypothesis: that all three solutes should
      increase c-Fos-like immunoreactivity (Fos-ir) inside the BBB, but that only NaCl
      should increase Fos-ir in the CVOs. We gave intravenous infusions of 3.0 Osm/l
      NaCl, glucose, or urea to rats for 11 or 22 min at 0.14 ml/min and perfused the
      rats for assay of Fos-ir at 90 min. Controls received isotonic NaCl at the same
      volume. Drinking latency was measured, but water was then removed. Drinking
      consistently occurred with short latency during hyperosmotic NaCl infusions only.
      Fos-ir in the forebrain CVOs, the subfornical organ, and organum vasculosum
      laminae terminalis was consistently elevated only by hyperosmotic NaCl. However,
      all three hyperosmotic solutes potently stimulated Fos-ir in the supraoptic and
      paraventricular nuclei of the hypothalamus inside the BBB. Hyperosmotic NaCl
      greatly elevated Fos-ir in the area postrema, but even glucose and urea caused
      moderate elevations that may be related to volume expansion rather than
      osmolality. The data provide strong support for the conclusion that the
      osmoreceptors controlling drinking are located in the CVOs.

PMID- 17194727
TI  - Effect of two different intense training regimens on skeletal muscle ion
      transport proteins and fatigue development.
AB  - This study examined the effect of two different intense exercise training
      regimens on skeletal muscle ion transport systems, performance, and metabolic
      response to exercise. Thirteen subjects performed either sprint training [ST; 6-s
      sprints (n = 6)], or speed endurance training [SET; 30-s runs approximately 130%
      Vo(2 max), n = 7]. Training in the SET group provoked higher (P < 0.05) plasma
      K(+) levels and muscle lactate/H(+) accumulation. Only in the SET group was the
      amount of the Na(+)/H(+) exchanger isoform 1 (31%) and Na(+)-K(+)-ATPase isoform
      alpha(2) (68%) elevated (P < 0.05) after training. Both groups had higher (P <
      0.05) levels of Na(+)-K(+)-ATPase beta(1)-isoform and monocarboxylate transporter
      1 (MCT1), but no change in MCT4 and Na(+)-K(+)-ATPase alpha(1)-isoform. Both
      groups had greater (P < 0.05) accumulation of lactate during exhaustive exercise
      and higher (P < 0.05) rates of muscle lactate decrease after exercise. The ST
      group improved (P < 0.05) sprint performance, whereas the SET group elevated (P <
      0.05) performance during exhaustive continuous treadmill running. Improvement in
      the Yo-Yo intermittent recovery test was larger (P < 0.05) in the SET than ST
      group (29% vs. 10%). Only the SET group had a decrease (P < 0.05) in fatigue
      index during a repeated sprint test. In conclusion, turnover of lactate/H(+) and
      K(+) in muscle during exercise does affect the adaptations of some but not all
      related muscle ion transport proteins with training. Adaptations with training do
      have an effect on the metabolic response to exercise and specific improvement in
      work capacity.

PMID- 17194728
TI  - Comments on point: counterpoint: "cardiovascular variability is/is not an index
      of autonomic control of circulation".

PMID- 17194729
TI  - Prevention of acute mountain sickness by acetazolamide: as yet an unfinished
      story.

PMID- 17194730
TI  - Decompression sickness in the rat following a dive on trimix: recompression
      therapy with oxygen vs. heliox and oxygen.
AB  - Trimix (a mixture of helium, nitrogen, and oxygen) has been used in deep diving
      to reduce the risk of high-pressure nervous syndrome during compression and the
      time required for decompression at the end of the dive. There is no specific
      recompression treatment for decompression sickness (DCS) resulting from trimix
      diving. Our purpose was to validate a rat model of DCS on decompression from a
      trimix dive and to compare recompression treatment with oxygen and heliox (helium
      oxygen). Rats were exposed to trimix in a hyperbaric chamber and tested for DCS
      while walking in a rotating wheel. We first established the experimental model,
      and then studied the effect of hyperbaric treatment on DCS: either hyperbaric
      oxygen (HBO) (1 h, 280 kPa oxygen) or heliox-HBO (0.5 h, 405 kPa heliox 50%-50%
      followed by 0.5 h, 280 kPa oxygen). Exposure to trimix was conducted at 1,110 kPa
      for 30 min, with a decompression rate of 100 kPa/min. Death and most DCS symptoms
      occurred during the 30-min period of walking. In contrast to humans, no permanent
      disability was found in the rats. Rats with a body mass of 100-150 g suffered no
      DCS. The risk of DCS in rats weighing 200-350 g increased linearly with body
      mass. Twenty-four hours after decompression, death rate was 40% in the control
      animals and zero in those treated immediately with HBO. When treatment was
      delayed by 5 min, death rate was 25 and 20% with HBO and heliox, respectively.

PMID- 17194731
TI  - The melting of pulmonary surfactant monolayers.
AB  - Monomolecular films of phospholipids in the liquid-expanded (LE) phase after
      supercompression to high surface pressures (pi), well above the equilibrium
      surface pressure (pi(e)) at which fluid films collapse from the interface to form
      a three-dimensional bulk phase, and in the tilted-condensed (TC) phase both
      replicate the resistance to collapse that is characteristic of alveolar films in
      the lungs. To provide the basis for determining which film is present in the
      alveolus, we measured the melting characteristics of monolayers containing TC
      dipalmitoyl phosphatidylcholine (DPPC), as well as supercompressed 1-palmitoyl-2
      oleoyl phosphatidylcholine and calf lung surfactant extract (CLSE). Films
      generated by appropriate manipulations on a captive bubble were heated from < or
      =27 degrees C to > or =60 degrees C at different constant pi above pi(e). DPPC
      showed the abrupt expansion expected for the TC-LE phase transition, followed by
      the contraction produced by collapse. Supercompressed CLSE showed no evidence of
      the TC-LE expansion, arguing that supercompression did not simply convert the
      mixed lipid film to TC DPPC. For both DPPC and CLSE, the melting point, taken as
      the temperature at which collapse began, increased at higher pi, in contrast to 1
      palmitoyl-2-oleoyl phosphatidylcholine, for which higher pi produced collapse at
      lower temperatures. For pi between 50 and 65 mN/m, DPPC melted at 48-55 degrees
      C, well above the main transition for bilayers at 41 degrees C. At each pi, CLSE
      melted at temperatures >10 degrees C lower. The distinct melting points for TC
      DPPC and supercompressed CLSE provide the basis by which the nature of the
      alveolar film might be determined from the temperature-dependence of pulmonary
      mechanics.

PMID- 17194732
TI  - Resveratrol attenuates oxLDL-stimulated NADPH oxidase activity and protects
      endothelial cells from oxidative functional damages.
AB  - trans-Resveratrol (RSV) has been shown to have cardioprotective effect during
      ischemia-reperfusion through reactive oxygen species (ROS)-scavenging activity.
      Elevated ROS has been implicated in the initiation and progression of
      atherosclerosis. The nicotinamide adenine dinucleotide phosphate oxidase (NOX) is
      a major source of vascular ROS formation. In the present study, we show that
      exposure of vascular endothelial cells (EC) to oxidized low-density lipoproteins
      (oxLDL) results in elevations of NOX activity and cellular ROS levels. The oxLDL
      effects are effectively suppressed by RSV or astringinin (AST), either before or
      after oxLDL exposure. In this study, we show that RSV or AST treatment appears to
      suppress NOX activity by reducing the membrane association of gp91(phox) and
      Rac1, two protein species required for the assembly of active NOX complex.
      Exposure to RSV or AST protects EC from oxidative functional damages, including
      antiplatelet activity and mononucleocyte adhesion. In addition, ANG II-induced
      NOX activation is also attenuated. These results suggest that RSV or AST protects
      EC from oxLDL-induced oxidative stress by both direct ROS scavenging and
      inhibition of NOX activity.

PMID- 17194733
TI  - Influence of static magnetic fields on pain perception and sympathetic nerve
      activity in humans.
AB  - Static and pulsed magnetic fields have been reported to have a variety of
      physiological effects. However, the effect of static magnetic fields on pain
      perception and sympathetic function is equivocal. To address this question, we
      measured pain perception during reproducible noxious stimuli during acute
      exposure to static magnets. Pain perception, muscle sympathetic nerve activity,
      mean arterial pressure, heart rate, and forearm blood velocity were measured
      during rest, isometric handgrip, postexercise muscle ischemia, and cold pressor
      test during magnet and placebo exposure in 15 subjects (25 +/- 1 yr; 8 men and 7
      women) following 1 h of exposure. During magnet exposure, subjects were placed on
      a mattress with 95 evenly spaced 0.06-T magnets imbedded in it. During placebo
      exposure, subjects were placed on an identical mattress without magnets. The
      order of the two exposure conditions was randomized. At rest, no significant
      differences were noted in muscle sympathetic nerve activity (8 +/- 1 and 7 +/- 1
      bursts/min for magnet and placebo, respectively), mean arterial pressure (91 +/-
      3 and 93 +/- 3 mmHg), heart rate (63 +/- 2 and 62 +/- 2 beats/min), and forearm
      blood velocity (3.0 +/- 0.3 and 2.6 +/- 0.3 cm/s). Magnets did not alter pain
      perception during the three stimuli. During all interventions, no significant
      differences between exposure conditions were found in muscle sympathetic nerve
      activity and hemodynamic measurements. These results indicate that acute exposure
      to static magnetic fields does not alter pain perception, sympathetic function,
      and hemodynamics at rest or during noxious stimuli.

PMID- 17194734
TI  - Critical role for adaptive T cell immunity in experimental eosinophilic
      esophagitis in mice.
AB  - We have previously developed a murine model of allergen-induced eosinophilic
      esophagitis (EE), characterized by intraepithelial eosinophils, extracellular
      granule deposition, and epithelial cell hyperplasia, features that mimic the
      pathophysiological changes observed in individuals with various forms of EE. We
      now test the hypothesis that adaptive T cell immunity is critical in initiating
      experimental EE. We first demonstrate that EE induction is associated with an
      increase in lymphocyte subpopulations (B+, CD4+, and CD8+ cells) in the
      esophagus. We induced experimental EE in wild-type and various lymphocyte
      subpopulation-deficient mice by intranasal allergen sensitization. Eosinophil
      levels and epithelial cell proliferation were determined by performing antimajor
      basic protein and antiproliferation cell nuclear antigen immunohistochemical
      analysis. Eosinophil accumulation in the esophagus was ablated completely in RAG1
      gene-deficient mice, but no role for B cells or antigen-specific antibodies was
      found, as B cell-deficient (IgH6) mice developed unabated, experimental EE. In
      addition, T cell-deficient (forkhead box N1-/-) mice were protected from the
      induction of experimental EE. CD8alpha-deficient mice developed unaltered,
      experimental EE, and CD4-deficient mice were only protected moderately from
      disease induction. Taken together, these studies indicate a role for CD4+ and CD4
      cell populations in EE pathogenesis and demonstrate that experimental allergen
      induced EE is dependent on adaptive T cell immunity.

PMID- 17194735
TI  - An eye's view of T regulatory cells.
AB  - T regulatory (Treg) cells have been studied for more than 30 years. Recently,
      changing technology and attitudes have led to new interest in T cell regulation
      of the immune responses. The eye is an immune-privileged site with unique
      mechanisms for the prevention of damaging immune inflammation. The eye fashions
      its Treg cells in novel ways to prevent immune inflammation locally and
      systemically. The purpose of this mini-review is to condense and summarize
      reports of Treg cells dependent on the eye in the context of the Treg literature
      in general.

PMID- 17194736
TI  - Role of the central melanocortin circuitry in adaptive thermogenesis of brown
      adipose tissue.
AB  - The central melanocortin 4 receptor (MC4R) plays a critical role in energy
      homeostasis, although little is known regarding its role in the regulation of
      adaptive thermogenesis of brown adipose tissue (BAT). Here we show using
      retrograde transsynaptic tracing with attenuated pseudorabies virus coupled with
      dual-label immunohistochemistry that specific subsets of MC4R-expressing neurons
      in multiple nuclei of the central nervous system known to regulate sympathetic
      outflow polysynaptically connect with interscapular BAT (IBAT). Furthermore, we
      show that MC4R-/- and agouti-related peptide-treated mice are defective in HF
      diet-induced up-regulation of uncoupling protein 1 in IBAT. Additionally, MC4R-/-
      mice exposed to 4 C for 4 h exhibit a defect in up-regulation of uncoupling
      protein 1 levels in IBAT. Our results provide a neuroanatomic substrate for MC4R
      regulating sympathetically mediated IBAT thermogenesis and demonstrate that the
      MC4R is critically required for acute high-fat- and cold-induced IBAT
      thermogenesis.

PMID- 17194737
TI  - N-procalcitonin: central effects on feeding and energy homeostasis in rats.
AB  - Procalcitonin (PCT), the precursor of calcitonin (CT), is a 116-amino-acid
      peptide, but PCT itself has no known activity. However, although the C cells of
      the thyroid gland are the dominant source of circulating CT, PCT and its free
      bioactive amino-terminal fragment (N-PCT) have been localized in adipocytes and
      neuroendocrine cells as well as in some hypothalamic regions of primary
      importance in the regulation of feeding and energy balance. These findings
      together with the coelaboration of N-PCT and CT, and N-PCT's sequence
      conservation during evolution, suggest that N-PCT has a critical, and as yet
      undefined, physiological function. We demonstrate here that
      intracerebroventricular administration of N-PCT significantly decreased food
      intake and body weight gain for at least 48 h in conscious, freely moving, and
      unstressed rats fed ad libitum. These effects were accompanied by a transitory
      increase in body temperature and a decrease in locomotor activity. Moreover,
      after intracerebroventricular N-PCT administration, Fos protein, a marker of
      neuronal activation, was found in regions of primary importance in the
      integration of hormonal signals for energy homeostasis and feeding. In contrast,
      ip administration of N-PCT did not elicit any anorectic or catabolic effects.
      Furthermore, PCT was found in key feeding areas such as the arcuate nucleus of
      free-feeding rats, and its level was significantly reduced after fasting. These
      results suggest that N-PCT can function as an endogenous ligand for the CT
      receptor and may act as a catabolic signaling molecule in the central regulation
      of feeding behavior and energy homeostasis.

PMID- 17194738
TI  - Corticotropin-releasing factor (CRF) and the urocortins differentially regulate
      catecholamine secretion in human and rat adrenals, in a CRF receptor type
      specific manner.
AB  - Corticotropin-releasing factor (CRF) affects catecholamine production both
      centrally and peripherally. The aim of the present work was to examine the
      presence of CRF, its related peptides, and their receptors in the medulla of
      human and rat adrenals and their direct effect on catecholamine synthesis and
      secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1
      (CRF1) and 2 (CRF2) were present in human and rat adrenal medulla as well as the
      PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT
      PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF1
      receptor agonists induced catecholamine secretion in a dose-dependent manner, an
      effect peaking at 30 min, whereas CRF2 receptor agonists suppressed catecholamine
      secretion. The respective effects were blocked by CRF1 and CRF2 antagonists. CRF
      peptides affected catecholamine secretion via changes of subplasmaliminal actin
      filament polymerization. CRF peptides also affected catecholamine synthesis. In
      rat chromaffin and PC12 cells, CRF1 and CRF2 agonists induced catecholamine
      synthesis via tyrosine hydroxylase. However, in human chromaffin cells,
      activation of CRF1 receptors induced tyrosine hydroxylase, whereas activation of
      CRF2 suppressed it. In conclusion, it appears that a complex intraadrenal CRF
      UCN/CRF-receptor system exists in both human and rat adrenals controlling
      catecholamine secretion and synthesis.

PMID- 17194739
TI  - Inhibin A is an endocrine stimulator of bone mass and strength.
AB  - Gonadal function plays a major role in bone homeostasis. It is widely held that
      the skeletal consequences of hypogonadism are solely due to a loss of sex
      steroids; however, increases in bone turnover begin during perimenopause before
      decreases in serum estradiol levels. These data and our demonstration that
      inhibins acutely regulate bone cell differentiation in vitro led us to test
      whether inhibin A (InhA) regulates bone mass in vivo. Using a transgenic model of
      inducible human InhA expression, InhA increased total body bone mineral density,
      increased bone volume, and improved biomechanical properties at the proximal
      tibia in intact mice and also prevented the loss of BMD and bone volume and
      strength associated with gonadectomy at both the spine and proximal tibia. In
      addition, InhA increased mineral apposition rate, double-labeled surface, and
      serum osteocalcin levels in vivo and osteoblastogenesis ex vivo without affecting
      osteoclast number or activity. Together these results demonstrate novel
      stimulatory effects of InhA on the skeleton in vivo. These studies provide in
      vivo evidence demonstrating that gonadal factors other than sex steroids play an
      important role in regulating bone mass and strength and, combined with our
      previous clinical data, suggest that gonadal InhA may be a component of the
      normal endocrine repertoire that regulates bone quality in both the axial and
      appendicular skeleton.

PMID- 17194740
TI  - Impact of periconceptional undernutrition on adrenal growth and adrenal insulin
      like growth factor and steroidogenic enzyme expression in the sheep fetus during
      early pregnancy.
AB  - Periconceptional undernutrition (PCUN) results in an earlier prepartum activation
      of the pituitary-adrenal axis in twin compared with singleton fetuses. We have
      tested the hypotheses that the functional development of the fetal sheep adrenal
      is delayed in twins compared with singletons in early gestation and that PCUN
      accelerates adrenal growth and increases the expression of intraadrenal IGF-I and
      -II and cytochrome P450 17-hydroxylase (CYP17) as early as 55 d gestation. We
      have investigated the effect of PCUN in the ewe (restricted at 70% of control
      allowance, n=21; control, n=24) from at least 45 d before mating until d 7 after
      mating on maternal cortisol and progesterone concentrations, fetal adrenal
      weight, adrenal IGF-I, IGF-I receptor (IGF-IR), IGF-II, IGF-IIR, and CYP17 mRNA
      expression and placental 11beta-hydroxysteroid dehydrogenase-1 and -2 mRNA and
      protein expression at d 53-56 pregnancy. The relative weight of the fetal adrenal
      and adrenal IGF-I, IGF-IR, IGF-II, IGF-IIR, and CYP17 mRNA expression were lower
      in twin compared with singleton fetuses. In singleton fetuses of PCUN ewes, there
      was a loss of the relationship between adrenal IGF-II/IGF-IIR expression and
      either adrenal weight or CYP17 mRNA, which was present in controls. Similarly in
      twin fetuses, PCUN resulted in the loss of the relationships between adrenal
      weight and IGF-I expression and between adrenal CYP17 and IGF-II expression,
      which were present in controls. Our findings suggest that differences in the
      timing of the prepartum activation of the fetal adrenal in twins and singletons
      have their origins in early gestation and highlight the importance of the
      interaction between the periconceptional environment and embryo number in setting
      the growth trajectory of the fetal adrenal.

PMID- 17194741
TI  - Proteomic profiling of cold thyroid nodules.
AB  - Cold thyroid nodules (CTNs) represent a frequent endocrine disorder accounting
      for up to 85% of thyroid nodules in a population living in an iodine-deficient
      area. Benign CTNs need to be distinguished from thyroid cancer, which is
      relatively rare. The molecular etiology of benign CTNs is unresolved. To obtain
      novel insights into their pathogenesis, protein expression profiling was
      performed in a series of 27 solitary CTNs (10 follicular adenoma and 20
      adenomatous nodules) and surrounding normal thyroid tissues using two-dimensional
      gel electrophoresis combined with mass spectrometry analysis, Western blotting,
      and immunohistochemistry. The proteome analysis revealed a specific fingerprint
      of CTNs with up-regulation of three functional systems: 1) thyroid cell
      proliferation, 2) turnover of thyroglobulin, and 3) H2O2 detoxification. Western
      blot analysis and immunohistochemistry confirmed the proteome data and showed
      that CTNs exhibit significant up-regulation of proteins involved in thyroid
      hormone synthesis yet are deficient in T4-containing thyroglobulin. This is
      consequential to intranodular iodide deficiency, mainly due to cytoplasmic sodium
      iodide symporter localization, and portrays the CTN as an activated proliferating
      lesion with an intranodular hypothyroid milieu. Furthermore, we provide
      preliminary evidence that up-regulation of H2O2 generation in CTNs could override
      the antioxidative system resulting in oxidative stress, which is suggested by the
      finding of raised 8-oxo-guanidine DNA adduct formation in CTNs.

PMID- 17194742
TI  - Endothelin-1 regulates adiponectin gene expression and secretion in 3T3-L1
      adipocytes via distinct signaling pathways.
AB  - Adiponectin, which is specifically and highly expressed in adipose tissue, has
      pleiotropic insulin-sensitizing effects. Endothelin-1 (ET-1) is a potent
      vasoconstrictive peptide mainly produced by endothelial cells. We previously
      showed that ET-1 can induce insulin resistance in vitro and in vivo and proposed
      that it might regulate adiponectin expression and secretion, thus affecting the
      homeostasis of whole-body energy metabolism. In the present study, we explored
      the regulatory effects of ET-1 on adiponectin expression and secretion and the
      underlying mechanisms in 3T3-L1 adipocytes using Northern blotting and ELISA. ET
      1 was found to cause a significant time- and dose-dependent decrease in
      adiponectin expression, and this effect was inhibited by the ET type A receptor
      (ETAR) antagonist BQ-610 but not by the ETBR antagonist BQ-788. To explore the
      underlying mechanism, we examined the involvement of the cAMP-dependent protein
      kinase A-, phospholipase A2-, protein kinase C-, and MAPK-mediated pathways using
      inhibitors and found that only PD98059 and U0126, inhibitors that blocked
      MAPK/ERK kinase's ability to activate the ERKs, prevented ET-1-induced down
      regulation of adiponectin. Furthermore, acute ET-1 treatment significantly
      stimulated adiponectin secretion by 3T3-L1 adipocytes, and this effect was
      inhibited by the ETAR antagonist BQ-610, the inositol-1,4,5-triphosphate receptor
      blocker 2-APB, and phospholipase C inhibitor U73122, showing that the release of
      adiponectin stimulated by ET-1 was mediated through the ETAR and the inositol
      1,4,5-triphosphate pathway. In conclusion, ET-1 regulates adiponectin expression
      and secretion by two different signaling pathways in 3T3-L1 adipocytes. These
      findings suggested that the cardiovascular system affects adipocyte physiology by
      regulating the expression of adipocytokines and, consequently, energy homeostasis
      via vasoactive factors, such as ET-1.

PMID- 17194743
TI  - Requirement of cannabinoid receptor type 1 for the basal modulation of
      hypothalamic-pituitary-adrenal axis function.
AB  - The endocannabinoid system affects the neuroendocrine regulation of hormone
      secretion, including the activity of the hypothalamus-pituitary-adrenal (HPA)
      axis. However, the mechanisms by which endocannabinoids regulate HPA axis
      function have remained unclear. Here we demonstrate that mice lacking cannabinoid
      receptor type 1 (CB1-/-) display a significant dysregulation of the HPA axis.
      Although circadian HPA axis responsiveness is preserved, CB1-/- mice are
      characterized by an enhanced circadian drive on the HPA axis, resulting in
      elevated plasma corticosterone concentrations at the onset of the dark as
      compared with wild-type (CB1+/+) littermates. Moreover, CB1-/--derived pituitary
      cells respond with a significantly higher ACTH secretion to CRH and forskolin
      challenges as compared with pituitary cells derived from CB1+/+ mice. Both CBL-/-
      and CB1+/+ mice properly respond to a high-dose dexamethasone test, but response
      to low-dose dexamethasone is influenced by genotype. In addition, CB1-/- mice
      show increased CRH mRNA levels in the paraventricular nucleus of the hypothalamus
      but not in other extrahypothalamic areas, such as the amygdala and piriform
      cortex, in which CB1 and CRH mRNA have been colocalized. Finally, CB1-/- mice
      have selective glucocorticoid receptor mRNA down-regulation in the CA1 region of
      the hippocampus but not in the dentate gyrus or paraventricular nucleus.
      Conversely, mineralocorticoid receptor mRNA expression levels were found
      unchanged in these brain areas. In conclusion, our findings indicate that CB1
      deficiency enhances the circadian HPA axis activity peak and leads to central
      impairment of glucocorticoid feedback, thus further outlining the essential role
      of the endocannabinoid system in the modulation of neuroendocrine functions.

PMID- 17194744
TI  - Activation of liver X receptors and retinoid X receptors induces growth arrest
      and apoptosis in insulin-secreting cells.
AB  - Liver X receptors (LXRs) form functional heterodimers with the retinoid X
      receptors (RXRs) and regulate cholesterol, lipid, and glucose metabolism. We
      demonstrated previously that activation of LXR modulates insulin secretion in
      MIN6 cells and pancreatic islets. In this study we investigated the effects of
      the LXR agonist T0901317 and the RXR agonist 9-cis-retinoic acid (9cRA) on cell
      proliferation and apoptosis in MIN6 cells. Whereas T0901317 showed no effect on
      proliferation of MIN6 cells, combination of T0901317 with 9cRA inhibited cell
      proliferation. Flow cytometry analysis of cell cycle demonstrated that activation
      of LXR/RXR prevented MIN6 cells from G1 to G2 phase progression. Combination of
      T0901317 and 9cRA increased apoptosis rate and caspase-3/7 activity in MIN6
      cells. Moreover, T0901317 or its combination with 9cRA significantly increased
      the cell susceptibility to free fatty acid- and cytokine-induced apoptosis.
      Treatment of MIN6 cells with LXR and RXR agonists produced a strong increase in
      expression of mothers against decapentaplegic homolog 3, a protein known to
      inhibit cell cycle G1/S phase progression and induce apoptosis. In isolated rat
      islets, the effect of palmitic acid on caspase-3/7 activity was increased with
      T0901317 alone and even more with the combination of T0901317 and 9cRA. Thus,
      activation of LXR/RXR signaling inhibits cell proliferation and induces apoptosis
      in pancreatic beta-cells.

PMID- 17194745
TI  - Ablation of the cholesterol transporter adenosine triphosphate-binding cassette
      transporter G1 reduces adipose cell size and protects against diet-induced
      obesity.
AB  - The ATP-binding cassette transporter G1 (ABCG1) catalyzes export of cellular
      cholesterol from macrophages and hepatocytes. Here we identify an additional
      function of ABCG1 in the regulation of adiposity in screens of the Drosophila
      melanogaster and the New Zealand obese (NZO) mouse genomes. Insertion of modified
      transposable elements of the P-family upstream of CG17646, the Drosophila
      ortholog of Abcg1, generated lines of flies with increased triglyceride stores.
      In NZO mice, an Abcg1 variant was identified in a suggestive adiposity
      quantitative trait locus and was associated with higher expression of the gene in
      white adipose tissue. Targeted disruption of Abcg1 in mice resulted in reduced
      body weight gain (8.42+/-0.6 g in Abcg1-/- vs. 13.07+/-1.1 g in Abcg1+/+ mice)
      and adipose tissue mass gain (3.78+/-1.3 g in Abcg1-/- vs. 9.39+/-1.6 g in
      Abcg1+/+ mice) detected over a period of 12 wk. The reduction of adipose tissue
      mass in Abcg1-/- mice was associated with markedly decreased size of the
      adipocytes. In contrast to their wild-type littermates, male Abcg1-/- mice
      exhibited no high-fat diet-induced impairment of glucose tolerance and fatty
      liver. Furthermore, Abcg1-/- mice possess decreased food intake and elevated
      total energy expenditure (Abcg1-/- mice, 748.1+/-5.4 kJ/kg metabolic body mass;
      Abcg1+/+ mice, 684.3+/-5.0 kJ/kg metabolic body mass; P=0.011), body temperature
      (Abcg1-/- mice, 37.82+/-0.29 C; Abcg1+/+ mice, 36.83+/-0.24 C; P<0.05), and
      locomotor activity (Abcg1-/- mice, 3655+/-189 counts/12 h during dark phase;
      Abcg1+/+ mice, 2445+/-235 counts/12 h during dark phase; P<0.01). Our data
      indicate a previously unrecognized role of ABCG1 in the regulation of energy
      balance and triglyceride storage.

PMID- 17194746
TI  - Development of primordial follicles in the hamster: role of estradiol-17beta.
AB  - The role of E2 on primordial follicle formation was examined by treating neonatal
      hamsters with 1 or 2 microg estradiol cypionate (ECP) at age postnatal d 1 (P1)
      and P4 or by in vitro culture of embryonic d 15 (E15) ovaries with 1, 5, or 10
      ng/ml estradiol-17beta (E2). The specificity of E2 action was examined by ICI
      182,780. One microgram of ECP maintained serum levels of E2 within the
      physiological range, significantly reduced apoptosis, and stimulated the
      formation and development of primordial follicles. In contrast, 2 microg ECP
      increased serum E2 levels to 400 pg/ml and had significantly less influence on
      primordial follicle formation. In vivo, ICI 182,780 significantly increased
      apoptosis and caused a modest reduction in primordial follicle formation. The
      formation and development of primordial follicles in vitro increased markedly
      with 1 ng/ml E2, and the effect was blocked by ICI 182,780. Higher doses of E2
      had no effect on primordial follicle formation but significantly up-regulated
      apoptosis, which was blocked by ICI 182,780. CYP19A1 mRNA expression occurred by
      E13 and increased with the formation of primordial follicles. P4 ovaries
      synthesized E2 from testosterone, which increased further by FSH. Both
      testosterone and FSH maintained ovarian CYP19A1 mRNA, but FSH up-regulated the
      expression. These results suggest that neonatal hamster ovaries produce E2 under
      FSH control and that E2 action is essential for the survival and differentiation
      of somatic cells and the oocytes leading to the formation and development of
      primordial follicles. This supportive action of E2 is lost when hormone levels
      increase above a threshold.

PMID- 17194748
TI  - Ambient air pollution and cardiovascular emergency department visits in
      potentially sensitive groups.
AB  - Limited evidence suggests that persons with conditions such as diabetes,
      hypertension, congestive heart failure, and respiratory conditions may be at
      increased risk of adverse cardiovascular morbidity and mortality associated with
      ambient air pollution. The authors collected data on over 4 million emergency
      department visits from 31 hospitals in Atlanta, Georgia, between January 1993 and
      August 2000. Visits for cardiovascular disease were examined in relation to
      levels of ambient pollutants by use of a case-crossover framework. Heterogeneity
      of risk was examined for several comorbid conditions. The results included
      evidence of stronger associations of dysrhythmia and congestive heart failure
      visits with comorbid hypertension in relation to increased air pollution levels
      compared with visits without comorbid hypertension; similar evidence of effect
      modification by diabetes and chronic obstructive pulmonary disease (COPD) was
      observed for dysrhythmia and peripheral and cerebrovascular disease visits,
      respectively. Evidence of effect modification by comorbid hypertension and
      diabetes was observed in relation to particulate matter less than 10 microm in
      aerodynamic diameter, nitrogen dioxide, and carbon monoxide, while evidence of
      effect modification by comorbid COPD was also observed in response to ozone
      levels. These findings provide further evidence of increased susceptibility to
      adverse cardiovascular events associated with ambient air pollution among persons
      with hypertension, diabetes, and COPD.

PMID- 17194747
TI  - Rapid inhibition of neurons in the dorsal motor nucleus of the vagus by leptin.
AB  - The peptide leptin conveys the availability of adipose energy stores to the
      brain. Increasing evidence implicates a significant role for extrahypothalamic
      sites of leptin action, including the dorsal vagal complex, a region critical for
      regulating visceral parasympathetic function. The hypothesis that leptin
      suppresses cellular activity in the dorsal motor nucleus of the vagus nerve (DMV)
      was tested using whole-cell patch-clamp recordings in brainstem slices. Leptin
      caused a rapid membrane hyperpolarization in 50% of rat DMV neurons. Leptin also
      hyperpolarized a subset of gastric-related neurons (62%), identified after
      gastric inoculation with a transneuronal retrograde viral tracer. The
      hyperpolarization was associated with a decrease in input resistance and cellular
      responsiveness and displayed characteristics consistent with an increased K+
      conductance. Perfusion of tolbutamide (200 microM) reversed the leptin-induced
      hyperpolarization, and tolbutamide or wortmannin (10-100 nM) prevented the
      hyperpolarization, indicating that leptin activated an ATP-sensitive K+ channel
      via a phosphoinositide-3-kinase-dependent mechanism. Leptin reduced the frequency
      of spontaneous and miniature excitatory postsynaptic currents (EPSCs), whereas
      inhibitory postsynaptic currents (IPSCs) were largely unaffected. Electrical
      stimulation of the nucleus tractus solitarii (NTS) resulted in constant-latency
      EPSCs, which were decreased in amplitude by leptin. The paired-pulse ratio was
      increased, suggesting leptin effects involved activation of receptors presynaptic
      to the recorded neuron. A leptin-induced suppression of EPSCs, but not IPSCs,
      evoked by focal photolytic uncaging of glutamate within the NTS was also
      observed, supportive of leptin effects on the glutamatergic NTS projection to the
      DMV. Therefore, leptin directly hyperpolarized and indirectly suppressed
      excitatory synaptic activity to DMV neurons involved in visceral regulation,
      including gastric-related neurons.

PMID- 17194749
TI  - Incident fall risk and physical activity and physical performance among older
      men: the Osteoporotic Fractures in Men Study.
AB  - Physical activity and physical performance have been linked to fall risk in the
      elderly. The authors examined the relation between physical activity and physical
      performance with incident falls in the Osteoporotic Fractures in Men Study, a
      large prospective cohort study of 5,995 community-dwelling men in the United
      States at least 65 years of age. The authors also examined what types of
      activities are associated with falling. Incident falls between 2000 and 2005 were
      captured from up to 17 triannual follow-up questionnaires per participant and
      analyzed with generalized estimating equations. Follow-up averaged 4.5 years. The
      average risk of falling in the first 4 months of follow-up was 6.6%. The most
      active quartile had a significantly greater fall risk than did the least active
      quartile (relative risk = 1.18, 95% confidence interval (CI): 1.07, 1.29). Men
      with greater leg power and grip strength had significantly reduced fall risk (for
      highest leg power quartile vs. lowest: relative risk = 0.82, 95% CI: 0.73, 0.92;
      for highest grip strength quartile vs. lowest: relative risk = 0.76, 95% CI:
      0.69, 0.85). Partitioning components of activity showed no association between
      fall risk and leisure activities but a positive association with household
      activities (for highest quartile vs.lowest: relative risk = 1.17, 95% CI: 1.07,
      1.28).

PMID- 17194750
TI  - A microRNA signature of hypoxia.
AB  - Recent research has identified critical roles for microRNAs in a large number of
      cellular processes, including tumorigenic transformation. While significant
      progress has been made towards understanding the mechanisms of gene regulation by
      microRNAs, much less is known about factors affecting the expression of these
      noncoding transcripts. Here, we demonstrate for the first time a functional link
      between hypoxia, a well-documented tumor microenvironment factor, and microRNA
      expression. Microarray-based expression profiles revealed that a specific
      spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210,
      and -213) is induced in response to low oxygen, at least some via a hypoxia
      inducible-factor-dependent mechanism. Select members of this group (miR-26, -107,
      and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an
      impact of these transcripts on tumor formation. Interestingly, the vast majority
      of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.

PMID- 17194751
TI  - Luteinizing hormone-dependent activation of the epidermal growth factor network
      is essential for ovulation.
AB  - In the preovulatory ovarian follicle, mammalian oocytes are maintained in
      prophase meiotic arrest until the luteinizing hormone (LH) surge induces reentry
      into the first meiotic division. Dramatic changes in the somatic cells
      surrounding the oocytes and in the follicular wall are also induced by LH and are
      necessary for ovulation. Here, we provide genetic evidence that LH-dependent
      transactivation of the epidermal growth factor receptor (EGFR) is indispensable
      for oocyte reentry into the meiotic cell cycle, for the synthesis of the
      extracellular matrix surrounding the oocyte that causes cumulus expansion, and
      for follicle rupture in vivo. Mice deficient in either amphiregulin or
      epiregulin, two EGFR ligands, display delayed or reduced oocyte maturation and
      cumulus expansion. In compound-mutant mice in which loss of one EGFR ligand is
      associated with decreased signaling from a hypomorphic allele of the EGFR, LH no
      longer signals oocyte meiotic resumption. Moreover, induction of genes involved
      in cumulus expansion and follicle rupture is compromised in these mice, resulting
      in impaired ovulation. Thus, these studies demonstrate that LH induction of
      epidermal growth factor-like growth factors and EGFR transactivation are
      essential for the regulation of a critical physiological process such as
      ovulation and provide new strategies for manipulation of fertility.

PMID- 17194752
TI  - Phosphorylation of MNAR promotes estrogen activation of phosphatidylinositol 3
      kinase.
AB  - Estrogen actions are mediated by a complex interface of direct control of gene
      expression (the so-called "genomic action") and by regulation of cell
      signaling/phosphorylation cascades, referred to as the "nongenomic," or
      extranuclear, action. We have previously described the identification of MNAR
      (modulator of nongenomic action of estrogen receptor) as a novel scaffold protein
      that regulates estrogen receptor alpha (ERalpha) activation of cSrc. In this
      study, we have investigated the role of MNAR in 17beta-estradiol (E2)-induced
      activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Consistent
      with our previous results, a direct correlation was established between MNAR
      expression levels and E2-induced activation of PI3 and Akt kinases. Endogenous
      MNAR, ERalpha, cSrc, and p85, the regulatory subunit of PI3 kinase, interacted in
      MCF7 cells treated with E2. The interaction between p85 and MNAR required
      activation of cSrc and MNAR phosphorylation on Tyr 920. Consequently, the
      mutation of this tyrosine to alanine (Y920A) abrogated the interaction between
      MNAR and p85 and the E2-induced activation of the PI3K/Akt pathway, which was
      required for the E2-induced protection of MCF7 cells from apoptosis. Nonetheless,
      the Y920A mutant potentiated the E2-induced activation of the Src/MAPK pathway
      and MCF7 cell proliferation, as observed with the wild-type MNAR. These results
      provide new and important insights into the molecular mechanisms of E2-induced
      regulation of cell proliferation and apoptosis.

PMID- 17194753
TI  - Specific phosphorylation of p120-catenin regulatory domain differently modulates
      its binding to RhoA.
AB  - p120-catenin is an adherens junction-associated protein that controls E-cadherin
      function and stability. p120-catenin also binds intracellular proteins, such as
      the small GTPase RhoA. In this paper, we identify the p120-catenin N-terminal
      regulatory domain as the docking site for RhoA. Moreover, we demonstrate that the
      binding of RhoA to p120-catenin is tightly controlled by the Src family-dependent
      phosphorylation of p120-catenin on tyrosine residues. The phosphorylation induced
      by Src and Fyn tyrosine kinases on p120-catenin induces opposite effects on RhoA
      binding. Fyn, by phosphorylating a residue located in the regulatory domain of
      p120-catenin (Tyr112), inhibits the interaction of this protein with RhoA. By
      contrast, the phosphorylation of Tyr217 and Tyr228 by Src promotes a better
      affinity of p120-catenin towards RhoA. In agreement with these biochemical data,
      results obtained in cell lines support the important role of these
      phosphorylation sites in the regulation of RhoA activity by p120-catenin. Taken
      together, these observations uncover a new regulatory mechanism acting on p120
      catenin that contributes to the fine-tuned regulation of the RhoA pathways during
      specific signaling events.

PMID- 17194754
TI  - Unphosphorylated H1 is enriched in a specific region of the promoter when CDC2 is
      down-regulated during starvation.
AB  - Tetrahymena thermophila macronuclear histone H1 is phosphorylated by a cdc2
      kinase, and H1 phosphorylation regulates CDC2 expression by a positive feedback
      mechanism. In starved wild-type cells, decreased expression of the CDC2 gene is
      correlated with a global reduction in the phosphorylation of H1 and reduced
      phosphorylation of H1 in the region upstream of the CDC2 gene. To determine
      whether the reduced H1 phosphorylation upstream of the CDC2 gene is merely a
      reflection of global dephosphorylation or is due to specific targeting of
      dephosphorylation of H1 to the CDC2 promoter during starvation, the CDC2 promoter
      was mapped, and the distributions of phosphorylated and unphosphorylated H1
      across the CDC2 gene were determined using chromatin immunoprecipitation.
      Unphosphorylated H1 is specifically enriched in a region of the CDC2 promoter
      when the gene's expression is reduced during starvation but not when CDC2 is
      highly active in growing cells. The region of unphosphorylated H1 coincides with
      a region that is essential for CDC2 expression. These studies are the first in
      vivo demonstration that the phosphorylation of H1 is being regulated at a fine
      level and that unphosphorylated H1 can be specifically targeted to a promoter,
      where it likely regulates transcription in a gene-specific manner.

PMID- 17194755
TI  - Lung development and repair: contribution of the ciliated lineage.
AB  - The identity of the endogenous epithelial cells in the adult lung that are
      responsible for normal turnover and repair after injury is still controversial.
      In part, this is due to a paucity of highly specific genetic lineage tools to
      follow efficiently the fate of the major epithelial cell populations: the basal,
      secretory, ciliated, neuroendocrine, and alveolar cells. As part of a program to
      address this problem we have used a 1-kb FOXJ1 promoter to drive CreER in the
      ciliated cells of the embryonic and adult lung. Analysis of FOXJ1-GFP transgenic
      lungs shows that labeled cells appear in a proximal-distal pattern during
      embryogenesis and that the promoter drives expression in all ciliated cells.
      Using FOXJ1CreER adult mice, we have followed the fate of ciliated cells after
      epithelial injury by naphthalene or sulfur dioxide. From quantitative analysis
      and confocal microscopy we conclude that ciliated cells transiently change their
      morphology in response to lung injury but do not proliferate or
      transdifferentiate as part of the repair process.

PMID- 17194756
TI  - Insights into finding a mismatch through the structure of a mispaired DNA bound
      by a rhodium intercalator.
AB  - We report the 1.1-A resolution crystal structure of a bulky rhodium complex bound
      to two different DNA sites, mismatched and matched in the oligonucleotide 5'
      (dCGGAAATTCCCG)2-3'. At the AC mismatch site, the structure reveals ligand
      insertion from the minor groove with ejection of both mismatched bases and
      elucidates how destabilized mispairs in DNA may be recognized. This unique
      binding mode contrasts with major groove intercalation, observed at a matched
      site, where doubling of the base pair rise accommodates stacking of the
      intercalator. Mass spectral analysis reveals different photocleavage products
      associated with the two binding modes in the crystal, with only products
      characteristic of mismatch binding in solution. This structure, illustrating two
      clearly distinct binding modes for a molecule with DNA, provides a rationale for
      the interrogation and detection of mismatches.

PMID- 17194757
TI  - Functionally important glycosyltransferase gain and loss during catarrhine
      primate emergence.
AB  - A glycosyltransferase, alpha1,3galactosyltransferase, catalyzes the terminal step
      in biosynthesis of Galalpha1,3Galbeta1-4GlcNAc-R (alphaGal), an oligosaccharide
      cell surface epitope. This epitope or antigenically similar epitopes are widely
      distributed among the different forms of life. Although abundant in most mammals,
      alphaGal is not normally found in catarrhine primates (Old World monkeys and
      apes, including humans), all of which produce anti-alphaGal antibodies from
      infancy onward. Natural selection favoring enhanced resistance to alphaGal
      positive pathogens has been the primary reason offered to account for the loss of
      alphaGal in catarrhines. Here, we question the primacy of this immune defense
      hypothesis with results that elucidate the evolutionary history of GGTA1 gene and
      pseudogene loci. One such locus, GGTA1P, a processed (intronless) pseudogene
      (PPG), is present in platyrrhines, i.e., New World monkeys, and catarrhines but
      not in prosimians. PPG arose in an early ancestor of anthropoids (catarrhines and
      platyrrhines), and GGTA1 itself became an unprocessed pseudogene in the late
      catarrhine stem lineage. Strong purifying selection, denoted by low nonsynonymous
      substitutions per nonsynonymous site/synonymous substitutions per synonymous site
      values, preserved GGTA1 in noncatarrhine mammals, indicating that the functional
      gene product is subjected to considerable physiological constraint. Thus, we
      propose that a pattern of alternative and/or more beneficial glycosyltransferase
      activity had to first evolve in the stem catarrhines before GGTA1 inactivation
      could occur. Enhanced defense against alphaGal-positive pathogens could then have
      accelerated the replacement of alphaGal-positive catarrhines by alphaGal-negative
      catarrhines. However, we emphasize that positively selected regulatory changes in
      sugar chain metabolism might well have contributed in a major way to catarrhine
      origins.

PMID- 17194758
TI  - Cyclin-dependent kinase 5 modulates nociceptive signaling through direct
      phosphorylation of transient receptor potential vanilloid 1.
AB  - Transient receptor potential vanilloid 1 (TRPV1), a ligand-gated cation channel
      highly expressed in small-diameter sensory neurons, is activated by heat,
      protons, and capsaicin. The phosphorylation of TRPV1 provides a versatile
      regulation of intracellular calcium levels and is critical for TRPV1 function in
      responding to a pain stimulus. We have previously reported that cyclin-dependent
      kinase 5 (Cdk5) activity regulates nociceptive signaling. In this article we
      report that the Cdk5-mediated phosphorylation of TRPV1 at threonine-407 can
      modulate agonist-induced calcium influx. Inhibition of Cdk5 activity in cultured
      dorsal root ganglia neurons resulted in a significant reduction of TRPV1-mediated
      calcium influx, and this effect could be reversed by restoring Cdk5 activity.
      Primary nociceptor-specific Cdk5 conditional-knockout mice showed reduced TRPV1
      phosphorylation, resulting in significant hypoalgesia. Thus, the present study
      indicates that Cdk5-mediated TRPV1 phosphorylation is important in the regulation
      of pain signaling.

PMID- 17194760
TI  - H2A.Z contributes to the unique 3D structure of the centromere.
AB  - Mammalian centromere function depends upon a specialized chromatin organization
      where distinct domains of CENP-A and dimethyl K4 histone H3, forming centric
      chromatin, are uniquely positioned on or near the surface of the chromosome.
      These distinct domains are embedded in pericentric heterochromatin (characterized
      by H3 methylated at K9). The mechanisms that underpin this complex spatial
      organization are unknown. Here, we identify the essential histone variant H2A.Z
      as a new structural component of the centromere. Along linear chromatin fibers
      H2A.Z is distributed nonuniformly throughout heterochromatin, and centric
      chromatin where regions of nucleosomes containing H2A.Z and dimethylated K4 H3
      are interspersed between subdomains of CENP-A. At metaphase, using the inactive X
      chromosome centromere as a model, complex folding of this fiber produces
      spatially positioned domains where H2A.Z/dimethylated K4 H3 chromatin juxtaposes
      one side of CENP-A chromatin, whereas a region of H2A/trimethyl K9 H3 borders the
      other side. A second region of H2A.Z is found, with trimethyl K9 H3 at the inner
      centromere. We therefore propose that H2A.Z plays an integral role in organizing
      centromere structure.

PMID- 17194759
TI  - Premature myogenic differentiation and depletion of progenitor cells cause severe
      muscle hypotrophy in Delta1 mutants.
AB  - In vertebrates, skeletal myogenesis is initiated by the generation of myoblasts
      followed by their differentiation to myocytes and the formation of myofibers. The
      determination of myoblasts and their differentiation are controlled by muscle
      regulatory factors that are activated at specific stages during myogenesis.
      During late embryonic and fetal stages a distinct population of resident
      proliferating progenitor cells is the major source of myogenic cells. How the
      differentiation of myoblasts and progenitor cells is regulated is not clear. We
      show that in mouse embryos the Notch ligand Delta1 (Dll1) controls both
      differentiation of early myoblasts and maintenance of myogenic progenitor cells.
      Early dermomyotome-derived myoblasts are determined normally in Dll1 mutant
      embryos, but their differentiation is accelerated, leading to a transient excess
      of myotomal muscle fibers. Similarly, migratory hypaxial myogenic cells colonize
      the limb buds and activate muscle regulatory factor expression normally, but
      muscle differentiation progresses more rapidly. Resident progenitor cells defined
      by Pax3/Pax7 expression are formed initially, but they are progressively lost and
      virtually absent at embryonic day 14.5. Muscle growth declines beginning around
      embryonic day 12, leading to subsequent severe muscle hypotrophy in hypomorphic
      Dll1 fetuses. We suggest that premature and excessive differentiation leads to
      depletion of progenitor cells and cessation of muscle growth, and we conclude
      that Dll1 provides essential signals that are required to prevent uncontrolled
      differentiation early and ensure sustained muscle differentiation during
      development.

PMID- 17194761
TI  - Structure of aspartoacylase, the brain enzyme impaired in Canavan disease.
AB  - Aspartoacylase catalyzes hydrolysis of N-acetyl-l-aspartate to aspartate and
      acetate in the vertebrate brain. Deficiency in this activity leads to spongiform
      degeneration of the white matter of the brain and is the established cause of
      Canavan disease, a fatal progressive leukodystrophy affecting young children. We
      present crystal structures of recombinant human and rat aspartoacylase refined to
      2.8- and 1.8-A resolution, respectively. The structures revealed that the N
      terminal domain of aspartoacylase adopts a protein fold similar to that of zinc
      dependent hydrolases related to carboxypeptidases A. The catalytic site of
      aspartoacylase shows close structural similarity to those of carboxypeptidases
      despite only 10-13% sequence identity between these proteins. About 100 C
      terminal residues of aspartoacylase form a globular domain with a two-stranded
      beta-sheet linker that wraps around the N-terminal domain. The long channel
      leading to the active site is formed by the interface of the N- and C-terminal
      domains. The C-terminal domain is positioned in a way that prevents productive
      binding of polypeptides in the active site. The structures revealed that residues
      158-164 may undergo a conformational change that results in opening and partial
      closing of the channel entrance. We hypothesize that the catalytic mechanism of
      aspartoacylase is closely analogous to that of carboxypeptidases. We identify
      residues involved in zinc coordination, and propose which residues may be
      involved in substrate binding and catalysis. The structures also provide a
      structural framework necessary for understanding the deleterious effects of many
      missense mutations of human aspartoacylase.

PMID- 17194762
TI  - D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to
      rapid activation of Gq/11 in the striatum.
AB  - We demonstrate a heteromeric D1-D2 dopamine receptor signaling complex in brain
      that is coupled to Gq/11 and requires agonist binding to both receptors for G
      protein activation and intracellular calcium release. The D1 agonist SKF83959 was
      identified as a specific agonist for the heteromer that activated Gq/11 by
      functioning as a full agonist for the D1 receptor and a high-affinity partial
      agonist for a pertussis toxin-resistant D2 receptor within the complex. We
      provide evidence that the D1-D2 signaling complex can be more readily detected in
      mice that are 8 months in age compared with animals that are 3 months old,
      suggesting that calcium signaling through the D1-D2 dopamine receptor complex is
      relevant for function in the postadolescent brain. Activation of Gq/11 through
      the heteromer increases levels of calcium/calmodulin-dependent protein kinase
      IIalpha in the nucleus accumbens, unlike activation of Gs/olf-coupled D1
      receptors, indicating a mechanism by which D1-D2 dopamine receptor complexes may
      contribute to synaptic plasticity.

PMID- 17194763
TI  - Genetic characterization and functional analysis of the GID1 gibberellin
      receptors in Arabidopsis.
AB  - We investigated the physiological function of three Arabidopsis thaliana homologs
      of the gibberellin (GA) receptor GIBBERELLIN-INSENSITIVE DWARF1 (GID1) by
      determining the developmental consequences of GID1 inactivation in insertion
      mutants. Although single mutants developed normally, gid1a gid1c and gid1a gid1b
      displayed reduced stem height and lower male fertility, respectively, indicating
      some functional specificity. The triple mutant displayed a dwarf phenotype more
      severe than that of the extreme GA-deficient mutant ga1-3. Flower formation
      occurred in long days but was delayed, with severe defects in floral organ
      development. The triple mutant did not respond to applied GA. All three GID1
      homologs were expressed in most tissues throughout development but differed in
      expression level. GA treatment reduced transcript abundance for all three GID1
      genes, suggesting feedback regulation. The DELLA protein REPRESSOR OF ga1-3 (RGA)
      accumulated in the triple mutant, whose phenotype could be partially rescued by
      loss of RGA function. Yeast two-hybrid and in vitro pull-down assays confirmed
      that GA enhances the interaction between GID1 and DELLA proteins. In addition,
      the N-terminal sequence containing the DELLA domain is necessary for GID1
      binding. Furthermore, yeast three-hybrid assays showed that the GA-GID1 complex
      promotes the interaction between RGA and the F-box protein SLY1, a component of
      the SCF(SLY1) E3 ubiquitin ligase that targets the DELLA protein for degradation.

PMID- 17194764
TI  - Structural basis for interaction of O-acetylserine sulfhydrylase and serine
      acetyltransferase in the Arabidopsis cysteine synthase complex.
AB  - In plants, association of O-acetylserine sulfhydrylase (OASS) and Ser
      acetyltransferase (SAT) into the Cys synthase complex plays a regulatory role in
      sulfur assimilation and Cys biosynthesis. We determined the crystal structure of
      Arabidopsis thaliana OASS (At-OASS) bound with a peptide corresponding to the C
      terminal 10 residues of Arabidopsis SAT (C10 peptide) at 2.9-A resolution.
      Hydrogen bonding interactions with key active site residues (Thr-74, Ser-75, and
      Gln-147) lock the C10 peptide in the binding site. C10 peptide binding blocks
      access to OASS catalytic residues, explaining how complex formation downregulates
      OASS activity. Comparison with bacterial OASS suggests that structural plasticity
      in the active site allows binding of SAT C termini with dissimilar sequences at
      structurally similar OASS active sites. Calorimetric analysis of the effect of
      active site mutations (T74S, S75A, S75T, and Q147A) demonstrates that these
      residues are important for C10 peptide binding and that changes at these
      positions disrupt communication between active sites in the homodimeric enzyme.
      We also demonstrate that the C-terminal Ile of the C10 peptide is required for
      molecular recognition by At-OASS. These results provide new insights into the
      molecular mechanism underlying formation of the Cys synthase complex and provide
      a structural basis for the biochemical regulation of Cys biosynthesis in plants.

PMID- 17194765
TI  - KEEP ON GOING, a RING E3 ligase essential for Arabidopsis growth and development,
      is involved in abscisic acid signaling.
AB  - Analysis of the Arabidopsis thaliana RING-ANK (for Really Interesting New Gene
      Ankyrin) family, a subgroup of RING-type E3 ligases, identified KEEP ON GOING
      (KEG) as essential for growth and development. In addition to the RING-HCa and
      ankyrin repeats, KEG contains a kinase domain and 12 HERC2-like repeats. The RING
      HCa and kinase domains were functional in in vitro ubiquitylation and
      phosphorylation assays, respectively. Seedlings homozygous for T-DNA insertions
      in KEG undergo growth arrest immediately after germination, suggestive of
      increased abscisic acid (ABA) signaling, a major phytohormone that plays a key
      role in plant development and survival under unfavorable conditions. Here, we
      show that KEG is a negative regulator of ABA signaling. keg roots are extremely
      sensitive to the inhibitory effects of ABA and exhibit hypersensitivity to
      exogenous glucose, consistent with the known interaction between glucose and ABA
      signaling. The observations that KEG accumulates high levels of ABSCISIC ACID
      INSENSITIVE5 (ABI5) without exogenous ABA, interacts with ABI5 in vitro, and that
      loss of ABI5 rescues the growth-arrest phenotype of keg mutant seedlings indicate
      that KEG is required for ABI5 degradation. In this capacity, KEG is central to
      ABA signaling by maintaining low levels of ABI5 in the absence of stress.

PMID- 17194766
TI  - Reduction of benzenoid synthesis in petunia flowers reveals multiple pathways to
      benzoic acid and enhancement in auxin transport.
AB  - In plants, benzoic acid (BA) is believed to be synthesized from Phe through
      shortening of the propyl side chain by two carbons. It is hypothesized that this
      chain shortening occurs via either a beta-oxidative or non-beta-oxidative
      pathway. Previous in vivo isotope labeling and metabolic flux analysis of the
      benzenoid network in petunia (Petunia hybrida) flowers revealed that both
      pathways yield benzenoid compounds and that benzylbenzoate is an intermediate
      between L-Phe and BA. To test this hypothesis, we generated transgenic petunia
      plants in which the expression of BPBT, the gene encoding the enzyme that uses
      benzoyl-CoA and benzyl alcohol to make benzylbenzoate, was reduced or eliminated.
      Elimination of benzylbenzoate formation decreased the endogenous pool of BA and
      methylbenzoate emission but increased emission of benzyl alcohol and
      benzylaldehyde, confirming the contribution of benzylbenzoate to BA formation.
      Labeling experiments with 2H5-Phe revealed a dilution of isotopic abundance in
      most measured compounds in the dark, suggesting an alternative pathway from a
      precursor other than Phe, possibly phenylpyruvate. Suppression of BPBT activity
      also affected the overall morphology of petunia plants, resulting in larger
      flowers and leaves, thicker stems, and longer internodes, which was consistent
      with the increased auxin transport in transgenic plants. This suggests that BPBT
      is involved in metabolic processes in vegetative tissues as well.

PMID- 17194767
TI  - MAIGO2 is involved in exit of seed storage proteins from the endoplasmic
      reticulum in Arabidopsis thaliana.
AB  - Seed storage proteins are synthesized on the endoplasmic reticulum (ER) as
      precursors and then transported to protein storage vacuoles, where they are
      processed into mature forms. Here, we isolated an Arabidopsis thaliana mutant,
      maigo2 (mag2), that accumulated the precursors of two major storage proteins, 2S
      albumin and 12S globulin, in dry seeds. mag2 seed cells contained many novel
      structures, with an electron-dense core that was composed of the precursor forms
      of 2S albumin. 12S globulins were segregated from 2S albumin and were localized
      in the matrix region of the structures together with the ER chaperones lumenal
      binding protein and protein disulfide isomerase, which were more abundant in mag2
      seeds. The MAG2 gene was identified as At3g47700, and the MAG2 protein had a RINT
      1/TIP20 domain in the C-terminal region. We found that some MAG2 molecules were
      peripherally associated with the ER membrane. MAG2 had an ability to bind to two
      ER-localized t-SNAREs (for target-soluble NSF [N-ethylmaleimide-sensitive fusion
      protein] attachment protein receptor; At Sec20 and At Ufe1). Our findings suggest
      that MAG2 functions in the transport of storage protein precursors between the ER
      and Golgi complex in plants.

PMID- 17194768
TI  - Phytotoxicity and innate immune responses induced by Nep1-like proteins.
AB  - We show that oomycete-derived Nep1 (for necrosis and ethylene-inducing peptide1)
      like proteins (NLPs) trigger a comprehensive immune response in Arabidopsis
      thaliana, comprising posttranslational activation of mitogen-activated protein
      kinase activity, deposition of callose, production of nitric oxide, reactive
      oxygen intermediates, ethylene, and the phytoalexin camalexin, as well as cell
      death. Transcript profiling experiments revealed that NLPs trigger extensive
      reprogramming of the Arabidopsis transcriptome closely resembling that evoked by
      bacteria-derived flagellin. NLP-induced cell death is an active, light-dependent
      process requiring HSP90 but not caspase activity, salicylic acid, jasmonic acid,
      ethylene, or functional SGT1a/SGT1b. Studies on animal, yeast, moss, and plant
      cells revealed that sensitivity to NLPs is not a general characteristic of
      phospholipid bilayer systems but appears to be restricted to dicot plants. NLP
      induced cell death does not require an intact plant cell wall, and ectopic
      expression of NLP in dicot plants resulted in cell death only when the protein
      was delivered to the apoplast. Our findings strongly suggest that NLP-induced
      necrosis requires interaction with a target site that is unique to the
      extracytoplasmic side of dicot plant plasma membranes. We propose that NLPs play
      dual roles in plant pathogen interactions as toxin-like virulence factors and as
      triggers of plant innate immune responses.

PMID- 17194771
TI  - An unusual pattern of spontaneous mutations recovered in the halophilic archaeon
      Haloferax volcanii.
AB  - Spontaneous mutations in the orotate:phosphoribosyl transferase (pyrE2) gene of
      the halophilic archaeon Haloferax volcanii were selected by 5-fluoroorotic acid
      plus uracil at a rate of approximately 2 x 10(-8)/cell division in fluctuation
      and null-fraction tests but approximately 6 x 10(-8)/cell division in mutation
      accumulation tests. The corresponding genomic mutation rates were substantially
      lower than those observed for other mesophilic microbial DNA genomes on the basis
      of similar target genes. The mutational spectrum was dominated by indels adding
      or deleting multiples of 3 bp. Properties of the organism contributing to this
      unusual mutational pattern may include phenotypic lag caused by a high
      chromosomal copy number and efficient promotion of strand misalignments by short
      direct repeats.

PMID- 17194769
TI  - Nonenzymatic lipid peroxidation reprograms gene expression and activates defense
      markers in Arabidopsis tocopherol-deficient mutants.
AB  - Tocopherols (vitamin E) are lipophilic antioxidants that are synthesized by all
      plants and are particularly abundant in seeds. Two tocopherol-deficient mutant
      loci in Arabidopsis thaliana were used to examine the functions of tocopherols in
      seedlings: vitamin e1 (vte1), which accumulates the pathway intermediate 2,3
      dimethyl-5-phytyl-1,4-benzoquinone (DMPBQ); and vte2, which lacks all tocopherols
      and pathway intermediates. Only vte2 displayed severe seedling growth defects,
      which corresponded with massively increased levels of the major classes of
      nonenzymatic lipid peroxidation products: hydroxy fatty acids, malondialdehyde,
      and phytoprostanes. In the absence of pathogens, the phytoalexin camalexin
      accumulated in vte2 seedlings to levels 100-fold higher than in wild-type or vte1
      seedlings. Similarly, gene expression profiling in wild-type, vte1, and vte2
      seedlings indicated that increased levels of nonenzymatic lipid peroxidation in
      vte2 corresponded to increased expression of many defense-related genes, which
      were not induced in vte1. Both biochemical and transcriptional analyses of vte2
      seedlings indicate that nonenzymatic lipid peroxidation plays a significant role
      in modulating plant defense responses. Together, these results establish that
      tocopherols in wild-type plants or DMPBQ in vte1 plants limit nonenzymatic lipid
      peroxidation during germination and early seedling development, thereby
      preventing the inappropriate activation of transcriptional and biochemical
      defense responses.

PMID- 17194770
TI  - The essential nature of sphingolipids in plants as revealed by the functional
      identification and characterization of the Arabidopsis LCB1 subunit of serine
      palmitoyltransferase.
AB  - Serine palmitoyltransferase (SPT) catalyzes the first step of sphingolipid
      biosynthesis. In yeast and mammalian cells, SPT is a heterodimer that consists of
      LCB1 and LCB2 subunits, which together form the active site of this enzyme. We
      show that the predicted gene for Arabidopsis thaliana LCB1 encodes a genuine
      subunit of SPT that rescues the sphingolipid long-chain base auxotrophy of
      Saccharomyces cerevisiae SPT mutants when coexpressed with Arabidopsis LCB2. In
      addition, homozygous T-DNA insertion mutants for At LCB1 were not recoverable,
      but viability was restored by complementation with the wild-type At LCB1 gene.
      Furthermore, partial RNA interference (RNAi) suppression of At LCB1 expression
      was accompanied by a marked reduction in plant size that resulted primarily from
      reduced cell expansion. Sphingolipid content on a weight basis was not changed
      significantly in the RNAi suppression plants, suggesting that plants compensate
      for the downregulation of sphingolipid synthesis by reduced growth. At LCB1 RNAi
      suppression plants also displayed altered leaf morphology and increases in
      relative amounts of saturated sphingolipid long-chain bases. These results
      demonstrate that plant SPT is a heteromeric enzyme and that sphingolipids are
      essential components of plant cells and contribute to growth and development.

PMID- 17194772
TI  - Substitution of critical isoleucines in the KH domains of Drosophila fragile X
      protein results in partial loss-of-function phenotypes.
AB  - Fragile X mental retardation proteins (FMRP) are RNA-binding proteins that
      interact with a subset of cellular RNAs. Several RNA-binding domains have been
      identified in FMRP, but the contribution of these individual domains to FMRP
      function in an animal model is not well understood. In this study, we have
      generated flies with point mutations in the KH domains of the Drosophila
      melanogaster fragile X gene (dfmr1) in the context of a genomic rescue fragment.
      The substitutions of conserved isoleucine residues within the KH domains with
      asparagine are thought to impair binding of RNA substrates and perhaps the
      ability of FMRP to assemble into mRNP complexes. The mutants were analyzed for
      defects in development and behavior that are associated with deletion null
      alleles of dfmr1. We find that these KH domain mutations result in partial loss
      of function or no significant loss of function for the phenotypes assayed. The
      phenotypes resulting from these KH domain mutants imply that the capacities of
      the mutant proteins to bind RNA and form functional mRNP complexes are not wholly
      disrupted and are consistent with biochemical models suggesting that RNA-binding
      domains of FMRP can function independently.

PMID- 17194774
TI  - Evolution of different Y chromosomes in two medaka species, Oryzias dancena and
      O. latipes.
AB  - Although the sex-determining gene DMY has been identified on the Y chromosome in
      the medaka (Oryzias latipes), this gene is absent in most Oryzias species,
      suggesting that closely related species have different sex-determining genes.
      Here, we investigated the sex-determination mechanism in O. dancena, which does
      not possess the DMY gene. Since heteromorphic sex chromosomes have not been
      reported in this species, a progeny test of sex-reversed individuals produced by
      hormone treatment was performed. Sex-reversed males yielded all-female progeny,
      indicating that O. dancena has an XX/XY sex-determination system. To uncover the
      cryptic sex chromosomes, sex-linked DNA markers were screened using expressed
      sequence tags (ESTs) established in O. latipes. Linkage analysis of isolated sex
      linked ESTs showed a conserved synteny between the sex chromosomes in O. dancena
      and an autosome in O. latipes. Fluorescence in situ hybridization (FISH) analysis
      of these markers confirmed that sex chromosomes of these species are not
      homologous. These findings strongly suggest an independent origin of sex
      chromosomes in O. dancena and O. latipes. Further analysis of the sex-determining
      region in O. dancena should provide crucial insights into the evolution of sex
      determination mechanisms in vertebrates.

PMID- 17194775
TI  - Cyclin and cyclin-dependent kinase substrate requirements for preventing
      rereplication reveal the need for concomitant activation and inhibition.
AB  - DNA replication initiation in S. cerevisiae is promoted by B-type cyclin
      dependent kinase (Cdk) activity. In addition, once-per-cell-cycle replication is
      enforced by cyclin-Cdk-dependent phosphorylation of the prereplicative complex
      (pre-RC) components Mcm2-7, Cdc6, and Orc1-6. Several of these controls must be
      simultaneously blocked by mutation to obtain rereplication. We looked for but did
      not obtain strong evidence for cyclin specificity in the use of different
      mechanisms to control rereplication: both the S-phase cyclin Clb5 and the mitotic
      cyclins Clb1-4 were inferred to be capable of imposing ORC-based and MCM-based
      controls. We found evidence that the S-phase cyclin Clb6 could promote initiation
      of replication without blocking reinitiation, and this activity was highly toxic
      when the ability of other cyclins to block reinitiation was prevented by
      mutation. The failure of Clb6 to regulate reinitiation was due to rapid Clb6
      proteolysis, since this toxic activity of Clb6 was lost when Clb6 was stabilized
      by mutation. Clb6-dependent toxicity is also relieved when early accumulation of
      mitotic cyclins is allowed to impose rereplication controls. Cell-cycle timing of
      rereplication control is crucial: sufficient rereplication block activity must be
      available as soon as firing begins. DNA rereplication induces DNA damage, and
      when rereplication controls are compromised, the DNA damage checkpoint factors
      Mre11 and Rad17 provide additional mechanisms that maintain viability and also
      prevent further rereplication, and this probably contributes to genome stability.

PMID- 17194777
TI  - Power to detect higher-order epistatic interactions in a metabolic pathway using
      a new mapping strategy.
AB  - Epistatic interactions among quantitative trait loci (QTL) contribute
      substantially to the variation in complex traits. The main objectives of this
      study were to (i) compare three- vs. four-step genome scans to identify three-way
      epistatic interactions among QTL belonging to a metabolic pathway, (ii)
      investigate by computer simulations the power and proportion of false positives
      (PFP) for detecting three-way interactions among QTL in recombinant inbred line
      (RIL) populations derived from a nested mating design, and (iii) compare these
      estimates to those obtained for detecting three-way interactions among QTL in RIL
      populations derived from diallel and different partial diallel mating designs.
      The single-nucleotide polymorphism haplotype data of B73 and 25 diverse maize
      inbreds were used to simulate the production of various RIL populations. Compared
      to the three-step genome scan, the power to detect three-way interactions was
      higher with the four-step genome scan. Higher power to detect three-way
      interactions was observed for RILs derived from optimally allocated distance
      based designs than from nested designs or diallel designs. The power and PFP to
      detect three-way interactions using a nested design with 5000 RILs were for both
      the 4-QTL and the 12-QTL scenario of a magnitude that seems promising for their
      identification.

PMID- 17194776
TI  - Drosophila ATR in double-strand break repair.
AB  - The ability of a cell to sense and respond to DNA damage is essential for genome
      stability. An important aspect of the response is arrest of the cell cycle,
      presumably to allow time for repair. Ataxia telangiectasia mutated (ATM) and ATR
      are essential for such cell-cycle control, but some observations suggest that
      they also play a direct role in DNA repair. The Drosophila ortholog of ATR, MEI
      41, mediates the DNA damage-dependent G2-M checkpoint. We examined the role of
      MEI-41 in repair of double-strand breaks (DSBs) induced by P-element excision. We
      found that mei-41 mutants are defective in completing the later steps of
      homologous recombination repair, but have no defects in end-joining repair. We
      hypothesized that these repair defects are the result of loss of checkpoint
      control. To test this, we genetically reduced mitotic cyclin levels and also
      examined repair in grp (DmChk1) and lok (DmChk2) mutants. Our results suggest
      that a significant component of the repair defects is due to loss of MEI-41
      dependent cell cycle regulation. However, this does not account for all of the
      defects we observed. We propose a novel role for MEI-41 in DSB repair,
      independent of the Chk1/Chk2-mediated checkpoint response.

PMID- 17194778
TI  - Consistent patterns of rate asymmetry and gene loss indicate widespread
      neofunctionalization of yeast genes after whole-genome duplication.
AB  - We investigated patterns of rate asymmetry in sequence evolution among the gene
      pairs (ohnologs) formed by whole-genome duplication (WGD) in yeast species. By
      comparing three species (Saccharomyces cerevisiae, Candida glabrata, and S.
      castellii) that underwent WGD to a nonduplicated outgroup (Kluyveromyces lactis),
      and by using a synteny framework to establish orthology and paralogy
      relationships at each duplicated locus, we show that 56% of ohnolog pairs show
      significantly asymmetric protein sequence evolution. For ohnolog pairs that
      remain duplicated in two species there is a strong tendency for the faster
      evolving copy in one species to be orthologous to the faster copy in the other
      species, which indicates that the evolutionary rate differences were established
      before speciation and hence soon after the WGD. We also present evidence that in
      cases where one ohnolog has been lost from the genome of a post-WGD species, the
      lost copy was likely to have been the faster-evolving member of the pair prior to
      its loss. These results suggest that a significant fraction of the retained
      ohnologs in yeast species underwent neofunctionalization soon after duplication.

PMID- 17194779
TI  - Comparative genomics and adaptive selection of the ATP-binding-cassette gene
      family in caenorhabditis species.
AB  - ABC transporters constitute one of the largest gene families in all species. They
      are mostly involved in transport of substrates across membranes. We have
      previously demonstrated that the Caenorhabditis elegans ABC family shows poor one
      to-one gene orthology with other distant model organisms. To address the
      evolution dynamics of this gene family among closely related species, we carried
      out a comparative analysis of the ABC family among the three nematode species C.
      elegans, C. briggsae, and C. remanei. In contrast to the previous observations,
      the majority of ABC genes in the three species were found in orthologous trios,
      including many tandemly duplicated ABC genes, indicating that the gene
      duplication took place before speciation. Species-specific expansions of ABC
      members are rare and mostly observed in subfamilies A and B. C. briggsae and C.
      remanei orthologous ABC genes tend to cluster on trees, with those of C. elegans
      as an outgroup, consistent with their proposed species phylogeny. Comparison of
      intron/exon structures of the highly conserved ABCE subfamily members also
      indicates a closer relationship between C. briggsae and C. remanei than between
      either of these species and C. elegans. A comparison between insect and mammalian
      species indicates lineage-specific duplications or deletions of ABC genes, while
      the family size remains relatively constant. Sites undergoing positive selection
      within subfamily D, which are implicated in very-long-chain fatty acid transport,
      were identified. The evolution of these sites might be driven by the changes in
      food source with time.

PMID- 17194780
TI  - A Distinct type of heterochromatin within Drosophila melanogaster chromosome 4.
AB  - Studies of transcriptional gene silencing in Drosophila melanogaster suggest that
      most of chromosome 4 resembles pericentric heterochromatin. However, some
      modifiers of position-effect variegation, including chromosome 4 dosage and loss
      of SU(VAR)3-9, have different effects on silencing in pericentric vs. distal arm
      chromosome 4 heterochromatin, distinguishing these two heterochromatin types.

PMID- 17194773
TI  - Five ovine mitochondrial lineages identified from sheep breeds of the near East.
AB  - Archaeozoological evidence indicates that sheep were first domesticated in the
      Fertile Crescent. To search for DNA sequence diversity arising from previously
      undetected domestication events, this survey examined nine breeds of sheep from
      modern-day Turkey and Israel. A total of 2027 bp of mitochondrial DNA (mtDNA)
      sequence from 197 sheep revealed a total of 85 haplotypes and a high level of
      genetic diversity. Six individuals carried three haplotypes, which clustered
      separately from the known ovine mtDNA lineages A, B, and C. Analysis of genetic
      distance, mismatch distribution, and comparisons with wild sheep confirmed that
      these represent two additional mtDNA lineages denoted D and E. The two haplogroup
      E sequences were found to link the previously identified groups A and C. The
      single haplogroup D sequence branched with the eastern mouflon (Ovis orientalis),
      urial (O. vignei), and argali (O. ammon) sheep. High sequence diversity (K =
      1.86%, haplogroup D and O. orientalis) indicates that the wild progenitor of this
      domestic lineage remains unresolved. The identification in this study of evidence
      for additional domestication events adds to the emerging view that sheep were
      recruited from wild populations multiple times in the same way as for other
      livestock species such as goat, cattle, and pig.

PMID- 17194781
TI  - Phylogenetic mapping of recombination hotspots in human immunodeficiency virus
      via spatially smoothed change-point processes.
AB  - We present a Bayesian framework for inferring spatial preferences of
      recombination from multiple putative recombinant nucleotide sequences.
      Phylogenetic recombination detection has been an active area of research for the
      last 15 years. However, only recently attempts to summarize information from
      several instances of recombination have been made. We propose a hierarchical
      model that allows for simultaneous inference of recombination breakpoint
      locations and spatial variation in recombination frequency. The dual multiple
      change-point model for phylogenetic recombination detection resides at the lowest
      level of our hierarchy under the umbrella of a common prior on breakpoint
      locations. The hierarchical prior allows for information about spatial
      preferences of recombination to be shared among individual data sets. To overcome
      the sparseness of breakpoint data, dictated by the modest number of available
      recombinant sequences, we a priori impose a biologically relevant correlation
      structure on recombination location log odds via a Gaussian Markov random field
      hyperprior. To examine the capabilities of our model to recover spatial variation
      in recombination frequency, we simulate recombination from a predefined
      distribution of breakpoint locations. We then proceed with the analysis of 42
      human immunodeficiency virus (HIV) intersubtype gag recombinants and identify a
      putative recombination hotspot.

PMID- 17194782
TI  - The carnegie protein trap library: a versatile tool for Drosophila developmental
      studies.
AB  - Metazoan physiology depends on intricate patterns of gene expression that remain
      poorly known. Using transposon mutagenesis in Drosophila, we constructed a
      library of 7404 protein trap and enhancer trap lines, the Carnegie collection, to
      facilitate gene expression mapping at single-cell resolution. By sequencing the
      genomic insertion sites, determining splicing patterns downstream of the enhanced
      green fluorescent protein (EGFP) exon, and analyzing expression patterns in the
      ovary and salivary gland, we found that 600-900 different genes are trapped in
      our collection. A core set of 244 lines trapped different identifiable protein
      isoforms, while insertions likely to act as GFP-enhancer traps were found in 256
      additional genes. At least 8 novel genes were also identified. Our results
      demonstrate that the Carnegie collection will be useful as a discovery tool in
      diverse areas of cell and developmental biology and suggest new strategies for
      greatly increasing the coverage of the Drosophila proteome with protein trap
      insertions.

PMID- 17194783
TI  - Natural genetic variation in cuticular hydrocarbon expression in male and female
      Drosophila melanogaster.
AB  - Cuticular hydrocarbons (CHCs) act as contact pheromones in Drosophila
      melanogaster and are an important component of several ecological traits.
      Segregating genetic variation in the expression of CHCs at the population level
      in D. melanogaster is likely to be important for mate choice and climatic
      adaptation; however, this variation has never been characterized. Using a panel
      of recombinant inbred lines (RILs) derived from a natural population, we found
      significant between-line variation for nearly all CHCs in both sexes. We
      identified 25 QTL in females and 15 QTL in males that pleiotropically influence
      CHC expression. There was no evidence of colocalization of QTL for homologous
      traits across the sexes, indicating that sexual dimorphism and low intersex
      genetic correlations between homologous CHCs are a consequence of largely
      independent genetic control. This is consistent with a pattern of divergent
      sexual and natural selection between the sexes.

PMID- 17194784
TI  - Background selection in single genes may explain patterns of codon bias.
AB  - Background selection involves the reduction in effective population size caused
      by the removal of recurrent deleterious mutations from a population. Previous
      work has examined this process for large genomic regions. Here we focus on the
      level of a single gene or small group of genes and investigate how the effects of
      background selection caused by nonsynonymous mutations are influenced by the
      lengths of coding sequences, the number and length of introns, intergenic
      distances, neighboring genes, mutation rate, and recombination rate. We generate
      our predictions from estimates of the distribution of the fitness effects of
      nonsynonymous mutations, obtained from DNA sequence diversity data in Drosophila.
      Results for genes in regions with typical frequencies of crossing over in
      Drosophila melanogaster suggest that background selection may influence the
      effective population sizes of different regions of the same gene, consistent with
      observed differences in codon usage bias along genes. It may also help to cause
      the observed effects of gene length and introns on codon usage. Gene conversion
      plays a crucial role in determining the sizes of these effects. The model
      overpredicts the effects of background selection with large groups of
      nonrecombining genes, because it ignores Hill-Robertson interference among the
      mutations involved.

PMID- 17194785
TI  - Genetic dissection of ethanol tolerance in the budding yeast Saccharomyces
      cerevisiae.
AB  - Uncovering genetic control of variation in ethanol tolerance in natural
      populations of yeast Saccharomyces cerevisiae is essential for understanding the
      evolution of fermentation, the dominant lifestyle of the species, and for
      improving efficiency of selection for strains with high ethanol tolerance, a
      character of great economic value for the brewing and biofuel industries. To
      date, as many as 251 genes have been predicted to be involved in influencing this
      character. Candidacy of these genes was determined from a tested phenotypic
      effect following gene knockout, from an induced change in gene function under an
      ethanol stress condition, or by mutagenesis. This article represents the first
      genomics approach for dissecting genetic variation in ethanol tolerance between
      two yeast strains with a highly divergent trait phenotype. We developed a simple
      but reliable experimental protocol for scoring the phenotype and a set of STR/SNP
      markers evenly covering the whole genome. We created a mapping population
      comprising 319 segregants from crossing the parental strains. On the basis of the
      data sets, we find that the tolerance trait has a high heritability and that
      additive genetic variance dominates genetic variation of the trait. Segregation
      at five QTL detected has explained approximately 50% of phenotypic variation; in
      particular, the major QTL mapped on yeast chromosome 9 has accounted for a
      quarter of the phenotypic variation. We integrated the QTL analysis with the
      predicted candidacy of ethanol resistance genes and found that only a few of
      these candidates fall in the QTL regions.

PMID- 17194786
TI  - Translation initiation in Saccharomyces cerevisiae mitochondria: functional
      interactions among mitochondrial ribosomal protein Rsm28p, initiation factor 2,
      methionyl-tRNA-formyltransferase and novel protein Rmd9p.
AB  - Rsm28p is a dispensable component of the mitochondrial ribosomal small subunit in
      Saccharomyces cerevisiae that is not related to known proteins found in bacteria.
      It was identified as a dominant suppressor of certain mitochondrial mutations
      that reduced translation of the COX2 mRNA. To explore further the function of
      Rsm28p, we isolated mutations in other genes that caused a synthetic respiratory
      defective phenotype together with rsm28Delta. These mutations identified three
      nuclear genes: IFM1, which encodes the mitochondrial translation initiation
      factor 2 (IF2); FMT1, which encodes the methionyl-tRNA-formyltransferase; and
      RMD9, a gene of unknown function. The observed genetic interactions strongly
      suggest that the ribosomal protein Rsm28p and Ifm1p (IF2) have similar and
      partially overlapping functions in yeast mitochondrial translation initiation.
      Rmd9p, bearing a TAP-tag, was localized to mitochondria and exhibited roughly
      equal distribution in soluble and membrane-bound fractions. A small fraction of
      the Rmd9-TAP sedimented together with presumed monosomes, but not with either
      individual ribosomal subunit. Thus, Rmd9 is not a ribosomal protein, but may be a
      novel factor associated with initiating monosomes. The poorly respiring
      rsm28Delta, rmd9-V363I double mutant did not have a strong translation-defective
      phenotype, suggesting that Rmd9p may function upstream of translation initiation,
      perhaps at the level of localization of mitochondrially coded mRNAs.

PMID- 17194787
TI  - Rmd9p controls the processing/stability of mitochondrial mRNAs and its
      overexpression compensates for a partial deficiency of oxa1p in Saccharomyces
      cerevisiae.
AB  - Oxa1p is a key component of the general membrane insertion machinery of
      eukaryotic respiratory complex subunits encoded by the mitochondrial genome. In
      this study, we have generated a respiratory-deficient mutant, oxa1-E65G-F229S,
      that contains two substitutions in the predicted intermembrane space domain of
      Oxa1p. The respiratory deficiency due to this mutation is compensated for by
      overexpressing RMD9. We show that Rmd9p is an extrinsic membrane protein facing
      the matrix side of the mitochondrial inner membrane. Its deletion leads to a
      pleiotropic effect on respiratory complex biogenesis. The steady-state level of
      all the mitochondrial mRNAs encoding respiratory complex subunits is strongly
      reduced in the Deltarmd9 mutant, and there is a slight decrease in the
      accumulation of two RNAs encoding components of the small subunit of the
      mitochondrial ribosome. Overexpressing RMD9 leads to an increase in the steady
      state level of mitochondrial RNAs, and we discuss how this increase could
      suppress the oxa1 mutations and compensate for the membrane insertion defect of
      the subunits encoded by these mRNAs.

PMID- 17194789
TI  - An extension of the transmission disequilibrium test incorporating imprinting.
AB  - The recombination rates in meioses of females and males are often different. Some
      genes that affect development and behavior in mammals are known to be imprinted,
      and >1% of all mammalian genes are believed to be imprinted. When the gene is
      imprinted and the recombination fractions are sex specific, the conventional
      transmission disequilibrium test (TDT) is shown to be still valid for testing for
      linkage. The power function of the TDT is derived, and the effect of the degree
      of imprinting on the power of the TDT is investigated. It is learned that
      imprinting has little effect on the power when the female and male recombination
      rates are equal. On the basis of case-parents trios, the transmissions from the
      heterozygous fathers/mothers to their affected children are separated as paternal
      and maternal, and two TDT-like statistics, TDT(p) and TDT(m), are consequently
      constructed. It is found that the TDT(p) possesses a higher power than the TDT
      for maternal imprinting genes, and the TDT(m) is more powerful than the TDT for
      paternal imprinting genes. On the basis of the parent-of-origin effects test
      statistic (POET), a novel statistic, TDT incorporating imprinting (TDTI) is
      proposed to test for linkage in the presence of linkage disequilibrium, which is
      shown to be more powerful than the TDT when parent-of-origin effects are
      significant but slightly less powerful than the TDT when parent-of-origin effects
      are negligible. The validity of the TDT and TDTI is assessed by simulation. The
      power approximation formulas for the TDT and TDTI are derived and the simulation
      results show that they are accurate. The simulation study on power comparison
      shows that the TDTI outperforms the TDT for imprinted genes. The improvement can
      be substantial in the case of complete paternal/maternal imprinting.

PMID- 17194790
TI  - Localization and characterization of X chromosome inversion breakpoints
      separating Drosophila mojavensis and Drosophila arizonae.
AB  - Ectopic exchange between transposable elements or other repetitive sequences
      along a chromosome can produce chromosomal inversions. As a result, genome
      sequence studies typically find sequence similarity between corresponding
      inversion breakpoint regions. Here, we identify and investigate the breakpoint
      regions of the X chromosome inversion distinguishing Drosophila mojavensis and
      Drosophila arizonae. We localize one inversion breakpoint to 13.7 kb and localize
      the other to a 1-Mb interval. Using this localization and assuming microsynteny
      between Drosophila melanogaster and D. arizonae, we pinpoint likely positions of
      the inversion breakpoints to windows of less than 3000 bp. These breakpoints
      define the size of the inversion to approximately 11 Mb. However, in contrast to
      many other studies, we fail to find significant sequence similarity between the 2
      breakpoint regions. The localization of these inversion breakpoints will
      facilitate future genetic and molecular evolutionary studies in this species
      group, an emerging model system for ecological genetics.

PMID- 17194788
TI  - The structure of linkage disequilibrium around a selective sweep.
AB  - The fixation of advantageous mutations by natural selection has a profound impact
      on patterns of linked neutral variation. While it has long been appreciated that
      such selective sweeps influence the frequency spectrum of nearby polymorphism, it
      has only recently become clear that they also have dramatic effects on local
      linkage disequilibrium. By extending previous results on the relationship between
      genealogical structure and linkage disequilibrium, I obtain simple expressions
      for the influence of a selective sweep on patterns of allelic association. I show
      that sweeps can increase, decrease, or even eliminate linkage disequilibrium (LD)
      entirely depending on the relative position of the selected and neutral loci. I
      also show the importance of the age of the neutral mutations in predicting their
      degree of association and describe the consequences of such results for the
      interpretation of empirical data. In particular, I demonstrate that while
      selective sweeps can eliminate LD, they generate patterns of genetic variation
      very different from those expected from recombination hotspots.

PMID- 17194791
TI  - Speciation in Drosophila: from phenotypes to molecules.
AB  - Study of the genetics of speciation--and especially of the genetics of intrinsic
      postzygotic isolation-has enjoyed remarkable progress over the last 2 decades.
      Indeed progress has been so rapid that one might be tempted to ask if the
      genetics of postzygotic isolation is now wrapped up. Here we argue that the
      genetics of speciation is far from complete. In particular, we review 2 topics
      where recent work has revealed major surprises: 1) the role of meiotic drive in
      hybrid sterility and 2) the role of gene transposition in speciation. These
      surprises, and others like them, suggest that evolutionary biologists may
      understand less about the genetic basis of speciation than seemed likely a few
      years ago.

PMID- 17194792
TI  - Colony spreading in Staphylococcus aureus.
AB  - Wild-type Staphylococcus aureus rapidly expands on the surface of soft agar
      plates. The rates of expansion and the shapes of the resultant giant colonies
      were distinct for different strains of laboratory stocks and clinical isolates.
      The colony spreading abilities did not correlate with the biofilm-forming
      abilities in these strains. Insertional disruption of the dltABCD operon, which
      functions at the step of D-alanine addition to teichoic acids, and of the tagO
      gene, which is responsible for the synthesis of wall teichoic acids, decreased
      the colony spreading ability. The results indicate that wall teichoic acids and D
      alanylation of teichoic acids are required for colony spreading.

PMID- 17194793
TI  - New functional identity for the DNA uptake sequence in transformation and its
      presence in transcriptional terminators.
AB  - The frequently occurring DNA uptake sequence (DUS), recognized as a 10-bp repeat,
      is required for efficient genetic transformation in the human pathogens Neisseria
      meningitidis and Neisseria gonorrhoeae. Genome scanning for DUS occurrences in
      three different species of Neisseria demonstrated that 76% of the nearly 2,000
      neisserial DUS were found to have two semiconserved base pairs extending from the
      5' end of DUS to constitute a 12-mer repeat. Plasmids containing sequential
      variants of the neisserial DUS were tested for their ability to transform N.
      meningitidis and N. gonorrhoeae, and the 12-mer was found to outperform the 10
      mer DUS in transformation efficiency. Assessment of meningococcal uptake of DNA
      confirmed the enhanced performance of the 12-mer compared to the 10-mer DUS. An
      inverted repeat DUS was not more efficient in transformation than DNA species
      containing a single or direct repeat DUS. Genome-wide analysis revealed that half
      of the nearly 1,500 12-mer DUS are arranged as inverted repeats predicted to be
      involved in rho-independent transcriptional termination or attenuation. The
      distribution of the uptake signal sequence required for transformation in the
      Pasteurellaceae was also biased towards transcriptional terminators, although to
      a lesser extent. In addition to assessing the intergenic location of DUS, we
      propose that the 10-mer identity of DUS should be extended and recognized as a 12
      mer DUS. The dual role of DUS in transformation and as a structural component on
      RNA affecting transcription makes this a relevant model system for assessing
      significant roles of repeat sequences in biology.

PMID- 17194794
TI  - Extensive and genome-wide changes in the transcription profile of Staphylococcus
      aureus induced by modulating the transcription of the cell wall synthesis gene
      murF.
AB  - A murF conditional mutant was used to evaluate the effect of suboptimal
      transcription of this gene on the transcriptome of the methicillin-resistant
      Staphylococcus aureus strain COL. The mutant was grown in the presence of optimal
      and suboptimal concentrations of the inducer, and the relative levels of
      transcription of genes were evaluated genome wide with an Affymetrix DNA
      microarray that included all open reading frames (ORFs) as well as intergenic
      sequences derived from four sequenced S. aureus strains. Using a sensitivity
      threshold value of 1.5, suboptimal expression of murF altered the transcription
      of a surprisingly large number of genes, i.e., 668 out of the 2,740 ORFs (close
      to one-fourth of all ORFs), of the genome of S. aureus strain COL. The genes with
      altered transcription were distributed evenly around the S. aureus chromosome,
      and groups of genes involved with distinct metabolic functions responded in
      unique and operon-specific manners to modulation in murF transcription. For
      instance, all genes belonging to the isd operon and all but 2 of the 35 genes of
      prophage L54a were down-regulated, whereas all but one of the 21 members of the
      vraSR regulon and most of the 79 virulence-related genes (those for fibronectin
      binding proteins A and B, clumping factor A, gamma hemolysin, enterotoxin B,
      etc.) were up-regulated in cells with suboptimal expression of murF. Most
      importantly, the majority of these altered gene expression profiles were
      reversible by resupplying the optimal concentration of IPTG (isopropyl-beta-D
      thiogalactopyranoside) to the culture. The observations suggest the coordinate
      regulation of a large sector of the S. aureus transcriptome in response to a
      disturbance in cell wall synthesis.

PMID- 17194796
TI  - Transposon Tn7 is widespread in diverse bacteria and forms genomic islands.
AB  - We find that relatives of the bacterial transposon Tn7 are widespread in
      disparate environments and phylogenetically diverse species. These elements form
      functionally diverse genomic islands at the specific site of Tn7 insertion
      adjacent to glmS. This work presents the first example of genomic island
      formation by a DDE type transposon.

PMID- 17194795
TI  - Diversity of the abundant pKLC102/PAGI-2 family of genomic islands in Pseudomonas
      aeruginosa.
AB  - The known genomic islands of Pseudomonas aeruginosa clone C strains are
      integrated into tRNA(Lys) (pKLC102) or tRNA(Gly) (PAGI-2 and PAGI-3) genes and
      differ from their core genomes by distinctive tetranucleotide usage patterns.
      pKLC102 and the related island PAPI-1 from P. aeruginosa PA14 were spontaneously
      mobilized from their host chromosomes at frequencies of 10% and 0.3%, making
      pKLC102 the most mobile genomic island known with a copy number of 30 episomal
      circular pKLC102 molecules per cell. The incidence of islands of the pKLC102/PAGI
      2 type was investigated in 71 unrelated P. aeruginosa strains from diverse
      habitats and geographic origins. pKLC102- and PAGI-2-like islands were identified
      in 50 and 31 strains, respectively, and 15 and 10 subtypes were differentiated by
      hybridization on pKLC102 and PAGI-2 macroarrays. The diversity of PAGI-2-type
      islands was mainly caused by one large block of strain-specific genes, whereas
      the diversity of pKLC102-type islands was primarily generated by subtype-specific
      combination of gene cassettes. Chromosomal loss of PAGI-2 could be documented in
      sequential P. aeruginosa isolates from individuals with cystic fibrosis. PAGI-2
      was present in most tested Cupriavidus metallidurans and Cupriavidus campinensis
      isolates from polluted environments, demonstrating the spread of PAGI-2 across
      habitats and species barriers. The pKLC102/PAGI-2 family is prevalent in numerous
      beta- and gammaproteobacteria and is characterized by high asymmetry of the cDNA
      strands. This evolutionarily ancient family of genomic islands retained its
      oligonucleotide signature during horizontal spread within and among taxa.

PMID- 17194797
TI  - Characterization of changes to the cell surface during the life cycle of
      Streptomyces coelicolor: atomic force microscopy of living cells.
AB  - Cell surface changes that accompany the complex life cycle of Streptomyces
      coelicolor were monitored by atomic force microscopy (AFM) of living cells.
      Images were obtained using tapping mode to reveal that young, branching
      vegetative hyphae have a relatively smooth surface and are attached to an inert
      silica surface by means of a secreted extracellular matrix. Older hyphae,
      representing a transition between substrate and aerial growth, are sparsely
      decorated with fibers. Previously, a well-organized stable mosaic of fibers,
      called the rodlet layer, coating the surface of spores has been observed using
      electron microscopy. AFM revealed that aerial hyphae, prior to sporulation,
      possess a relatively unstable dense heterogeneous fibrous layer. Material from
      this layer is shed as the hyphae mature, revealing a more tightly organized
      fibrous mosaic layer typical of spores. The aerial hyphae are also characterized
      by the absence of the secreted extracellular matrix. The formation of sporulation
      septa is accompanied by modification to the surface layer, which undergoes
      localized temporary disruption at the sites of cell division. The characteristics
      of the hyphal surfaces of mutants show how various chaplin and rodlin proteins
      contribute to the formation of fibrous layers of differing stabilities. Finally,
      older spores with a compact rodlet layer develop surface concavities that are
      attributed to a reduction of intracellular turgor pressure as metabolic activity
      slows.

PMID- 17194798
TI  - Anti-inflammatory mechanisms of isoflavone metabolites in lipopolysaccharide
      stimulated microglial cells.
AB  - The microglial activation plays an important role in neurodegenerative diseases
      by producing several proinflammatory cytokines and nitric oxide (NO). We found
      that three types of isoflavones and their metabolites that are transformed by the
      human intestinal microflora suppress lipopolysaccharide (LPS)-induced release of
      NO and tumor necrosis factor (TNF)-alpha in primary cultured microglia and BV2
      microglial cell lines. The inhibitory effect of the isoflavone metabolites
      (aglycon form) was more potent than that of isoflavones (glycoside form). The
      RNase protection assay showed that the isoflavone metabolites regulated inducible
      nitric oxide synthase (iNOS) and the cytokines at either the transcriptional or
      post-transcriptional level. A further molecular mechanism study was performed for
      irisolidone, a metabolite of kakkalide, which had the most potent anti
      inflammatory effect among the six isoflavones tested. Irisolidone significantly
      inhibited the DNA binding and transcriptional activity of nuclear factor (NF)
      kappaB and activator protein-1. Moreover, it repressed the LPS-induced
      extracellular signal-regulated kinase (ERK) phosphorylation without affecting the
      activity of c-Jun N-terminal kinase or p38 mitogen-activated protein kinase. The
      level of NF-kappaB inhibition by irisolidone correlated with the level of iNOS,
      TNF-alpha, and interleukin (IL)-1beta suppression in LPS-stimulated microglia,
      whereas the level of ERK inhibition correlated with the level of TNF-alpha and IL
      1beta repression. Overall, the repression of proinflammatory cytokines and iNOS
      gene expression in activated microglia by isoflavones such as irisolidone might
      have therapeutic potential for various neurodegenerative diseases including
      ischemic cerebral disease.

PMID- 17194799
TI  - Differential effects of antipsychotic drugs on serotonin-1A receptor-mediated
      disruption of prepulse inhibition.
AB  - Serotonin-1A (5-HT(1A)) receptors have been implicated in the symptoms of
      schizophrenia. However, there is limited in vivo evidence for an interaction of
      antipsychotic drugs with 5-HT(1A) receptor-mediated behavioral effects. We
      therefore investigated in rats the action of several antipsychotic drugs on
      prepulse inhibition (PPI), a measure of sensorimotor gating that is deficient in
      schizophrenia. Disruption of PPI at the 100-ms interstimulus interval (ISI), but
      not the 30-ms ISI, was induced by treatment with 0.5 mg/kg 8-hydroxy-di
      propylaminotetralin (8-OH-DPAT), the 5-HT(1A) receptor agonist. In rats
      pretreated with 0.25 mg/kg haloperidol (4-[-4-(p-chlorophenyl)-4
      hydroxypiperidino]-4'-fluoro butyrophenone) or raclopride [3,5-dichloro-N-(1
      ethylpyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxybenzamide tartrate], the
      disruption of PPI was no longer significant. Of the atypical antipsychotic drugs
      clozapine (8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]-diazepine),
      olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3
      b][1,5]benzodiazepine), risperidone [3-[2-[-4-(6-fluoro-1,2-benzisoxazol-3-yl)
      piperidino] ethyl-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one)],
      amisulpride (4-amino-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-o
      anisamide), and aripiprazole (7-[4-[-4[-(2,3-dichlorophenyl)-1
      piperazinyl]butoxy]-3,4-dihydrocarbostyrilor 7-[4-[4-(2,3-dichlorophenyl)
      piperazin-1-yl]butoxy]-1,2,3,4,-tetrahydroquinolin-2-one), only aripiprazole
      significantly reduced the effect of 8-OH-DPAT on PPI. This effect was mimicked by
      pretreatment with the 5-HT(1A) receptor partial agonist, buspirone [N-[4-[4-(2
      pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione hydrochloride].
      On the other hand, some of the antipsychotic drugs and other pretreatments showed
      complex, prepulse-dependent effects on their own. These data show little in vivo
      interaction of several atypical antipsychotic drugs with the disruption of PPI
      mediated by 5-HT(1A) receptor stimulation. The action of haloperidol and
      raclopride suggests a major involvement of dopamine D(2) receptors in this
      effect, possibly downstream from the initial serotonergic stimulation. The action
      of aripiprazole could be mediated by its partial agonist properties at 5-HT(1A)
      receptors or its dopamine D(2)-blocking properties.

PMID- 17194800
TI  - A novel role of cannabinoids: implication in the fever induced by bacterial
      lipopolysaccharide.
AB  - There is continuing interest in elucidating the actions of drugs of abuse on the
      immune system and on infection. The present study investigated the effects of the
      cannabinoid (CB) receptor agonist aminoalkylindole, (+)-WIN 55,212-2 [(4,5
      dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H
      pyrrolo[3,2,1ij]quinolin-6-one], on fever produced after injection of
      lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative
      bacteria, the best known and most frequently used experimental model.
      Intraperitoneal injection of LPS (50 mug/kg) induced a biphasic fever, with the
      first peak at 180 min and the second at 300 min postinjection. Pretreatment with
      a nonhypothermic dose of the cannabinoid receptor agonist WIN 55,212-2 (0.5-1.5
      mg/kg i.p.) antagonized the LPS-induced fever. However, pretreatment with the
      inactive enantiomer WIN 55,212-3 [1.5 mg/kg i.p.; S-(-)-[2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1
      naphthanlenyl)methanone mesylate] did not. The inhibitory effect of WIN 55,212-2
      on LPS-induced fever was reversed by SR141716 [N-(piperdin-1-yl)-5-(4
      chloropheny)-1-(2,4-dichloropheny)-4-methyl-1H-pyrazole-3-carboxamide
      hydrochloride], a selective CB1 receptor antagonist, but not by SR144528 (N-[(1S)
      endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]5-(4-choro-3-methylphenyl)-1-(4
      methylbenzyl)pyrazole-3-carboxamide), a selective antagonist at the CB2 receptor.
      The present results show that cannabinoids interact with systemic bacterial LPS
      injection and indicate a role of the CB1 receptor subtype in the pathogenesis of
      LPS fever.

PMID- 17194802
TI  - Whole-mtDNA genome sequence analysis of ancient African lineages.
AB  - Studies of human mitochondrial (mt) DNA genomes demonstrate that the root of the
      human phylogenetic tree occurs in Africa. Although 2 mtDNA lineages with an
      African origin (haplogroups M and N) were the progenitors of all non-African
      haplogroups, macrohaplogroup L (including haplogroups L0-L6) is limited to sub
      Saharan Africa. Several L haplogroup lineages occur most frequently in eastern
      Africa (e.g., L0a, L0f, L5, and L3g), but some are specific to certain ethnic
      groups, such as haplogroup lineages L0d and L0k that previously have been found
      nearly exclusively among southern African "click" speakers. Few studies have
      included multiple mtDNA genome samples belonging to haplogroups that occur in
      eastern and southern Africa but are rare or absent elsewhere. This lack of
      sampling in eastern Africa makes it difficult to infer relationships among mtDNA
      haplogroups or to examine events that occurred early in human history. We
      sequenced 62 complete mtDNA genomes of ethnically diverse Tanzanians, southern
      African Khoisan speakers, and Bakola Pygmies and compared them with a global pool
      of 226 mtDNA genomes. From these, we infer phylogenetic relationships amongst
      mtDNA haplogroups and estimate the time to most recent common ancestor (TMRCA)
      for haplogroup lineages. These data suggest that Tanzanians have high genetic
      diversity and possess ancient mtDNA haplogroups, some of which are either rare
      (L0d and L5) or absent (L0f) in other regions of Africa. We propose that a large
      and diverse human population has persisted in eastern Africa and that eastern
      Africa may have been an ancient source of dispersion of modern humans both within
      and outside of Africa.

PMID- 17194801
TI  - One billion years of bZIP transcription factor evolution: conservation and change
      in dimerization and DNA-binding site specificity.
AB  - The genomic era has revealed that the large repertoire of observed animal
      phenotypes is dependent on changes in the expression patterns of a finite number
      of genes, which are mediated by a plethora of transcription factors (TFs) with
      distinct specificities. The dimerization of TFs can also increase the complexity
      of a genetic regulatory network manifold, by combining a small number of monomers
      into dimers with distinct functions. Therefore, studying the evolution of these
      dimerizing TFs is vital for understanding how complexity increased during animal
      evolution. We focus on the second largest family of dimerizing TFs, the basic
      region leucine zipper (bZIP), and infer when it expanded and how bZIP DNA-binding
      and dimerization functions evolved during the major phases of animal evolution.
      Specifically, we classify the metazoan bZIPs into 19 families and confirm the
      ancient nature of at least 13 of these families, predating the split of the
      cnidaria. We observe fixation of a core dimerization network in the last common
      ancestor of protostomes-deuterostomes. This was followed by an expansion of the
      number of proteins in the network, but no major dimerization changes in
      interaction partners, during the emergence of vertebrates. In conclusion, the
      bZIPs are an excellent model with which to understand how DNA binding and protein
      interactions of TFs evolved during animal evolution.

PMID- 17194803
TI  - Genetic toxicity assessment: employing the best science for human safety
      evaluation. Part I: Early screening for potential human mutagens.
AB  - Results of genetic toxicology tests are used by FDA's Center for Drug Evaluation
      and Research as a surrogate for carcinogenicity data during the drug development
      process. Mammalian in vitro assays have a high frequency of positive results
      which can impede or derail the drug development process. To reduce the risk of
      such delays, most pharmaceutical companies conduct early non-GLP (good laboratory
      practices) studies to eliminate drug candidate with mutagenic or clastogenic
      activity. Early screens include in silico structure activity assessments and
      various iterations of the ultimate regulatory mandated GLP studies.

PMID- 17194804
TI  - Simultaneous induction of apoptotic and survival signaling pathways in macrophage
      like THP-1 cells by Shiga toxin 1.
AB  - Shiga toxins have been shown to induce apoptosis in many cell types. However,
      Shiga toxin 1 (Stx1) induced only limited apoptosis of macrophage-like THP-1
      cells in vitro. The mechanisms regulating macrophage death or survival following
      toxin challenge are unknown. Differentiated THP-1 cells expressed tumor necrosis
      factor receptors and membrane-associated tumor necrosis factor alpha (TNF-alpha)
      and produced soluble TNF-alpha after exposure to Stx1. However, the cells were
      refractory to apoptosis induced by TNF-alpha, although the cytokine modestly
      increased apoptosis in the presence of Stx1. Despite the partial resistance of
      macrophage-like THP-1 cells to Stx1-mediated killing, treatment of these cells
      with Stx1 activated a broad array of caspases, disrupted the mitochondrial
      membrane potential (DeltaPsi(m)), and released cytochrome c into the cytoplasm.
      The DeltaPsi(m) values were greatest in cells that had detached from plastic
      surfaces. Specific caspase inhibitors revealed that caspase-3, caspase-6, caspase
      8, and caspase-9 were primarily involved in apoptosis induction. The
      antiapoptotic factors involved in macrophage survival following toxin challenge
      include inhibitors of apoptosis proteins and X-linked inhibitor of apoptosis
      protein. NF-kappaB and JNK mitogen-activated protein kinases (MAPKs) appeared to
      activate survival pathways, while p38 MAPK was involved in proapoptotic
      signaling. The JNK and p38 MAPKs were shown to be upstream signaling pathways
      which may regulate caspase activation. Finally, the protein synthesis inhibitors
      Stx1 and anisomycin triggered limited apoptosis and prolonged JNK and p38 MAPK
      activation, while macrophage-like cells treated with cycloheximide remained
      viable and showed transient activation of MAPKs. Collectively, these data suggest
      that Stx1 activates both apoptotic and cell survival signaling pathways in
      macrophage-like THP-1 cells.

PMID- 17194805
TI  - Helicobacter pylori CagA induces AGS cell elongation through a cell retraction
      defect that is independent of Cdc42, Rac1, and Arp2/3.
AB  - Helicobacter pylori, which infects over one-half the world's population, is a
      significant risk factor in a spectrum of gastric diseases, including peptic
      ulcers and gastric cancer. Strains of H. pylori that deliver the effector
      molecule CagA into host cells via a type IV secretion system are associated with
      more severe disease outcomes. In a tissue culture model of infection, CagA
      delivery results in a dramatic cellular elongation referred to as the
      "hummingbird" phenotype, which is characterized by long, thin cellular
      extensions. These actin-based cytoskeletal rearrangements are reminiscent of
      structures that are regulated by Rho GTPases and the Arp2/3 complex. We tested
      whether these signaling pathways were important in the H. pylori-induced cell
      elongation phenotype. Contrary to our expectations, we found that these molecules
      are dispensable for cell elongation. Instead, time-lapse video microscopy
      revealed that cells infected by cagA(+) H. pylori become elongated because they
      fail to release their back ends during cell locomotion. Consistent with a model
      in which CagA causes cell elongation by inhibiting the disassembly of adhesive
      cell contacts at migrating cells' lagging ends, immunohistochemical analysis
      revealed that focal adhesion complexes persist at the distal tips of elongated
      cell projections. Thus, our data implicate a set of signaling molecules in the
      hummingbird phenotype that are different than the molecules previously suspected.

PMID- 17194806
TI  - Identification of the mycobacterial subcomponents involved in the release of
      tumor necrosis factor-related apoptosis-inducing ligand from human neutrophils.
AB  - Intravesical administration of Mycobacterium bovis bacillus Calmette-Guerin (BCG)
      continues to be a successful immunotherapy for superficial bladder cancer.
      Recently, workers in our laboratory observed expression of tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) on neutrophils in voided urine
      following BCG therapy. Neutrophils released a soluble and functional form of
      TRAIL when they were stimulated in vitro with BCG, and the activity was localized
      predominantly to the cell wall fraction. In this study, we examined the ability
      of individual mycobacterial components to stimulate TRAIL release from
      neutrophils. Our results demonstrated that cell wall-derived lipoarabinomannan
      (LAM), mycolyl arabinogalactan-peptidoglycan complex, and a Triton X-114 (Tx114)
      solubilized protein pool were effective agonists of TRAIL release from
      neutrophils. Mycobacterial DNA was also an agonist of TRAIL release from
      neutrophils. Furthermore, purified antigen 85 ABC complex and alpha-crystallin
      (HspX), two major cell wall antigens present in the Tx114 pool, induced TRAIL
      release from neutrophils. The Tx114 pool stimulated HEK-293 cells expressing
      either Toll-like receptor 2/1 (TLR2/1) or TLR2/6, but only HspX was able to
      stimulate TLR2/6-expressing cells. TLR4/MD2/CD14-expressing cells responded only
      to LAM. Collectively, these results suggested that TRAIL release from neutrophils
      was induced through the recognition of multiple mycobacterial components by TLR2
      and TLR4.

PMID- 17194807
TI  - "Candidatus Helicobacter heilmannii" from a cynomolgus monkey induces gastric
      mucosa-associated lymphoid tissue lymphomas in C57BL/6 mice.
AB  - Both Helicobacter pylori and "Candidatus Helicobacter heilmannii" infections are
      associated with peptic ulcers, gastric adenocarcinoma, and gastric mucosa
      associated lymphoid tissue (MALT) lymphomas. However, good animal models of H.
      pylori clinical diseases are rare. In this study, we aimed to establish an animal
      model of "Candidatus Helicobacter heilmannii" gastric MALT lymphoma. We used a
      urease-positive gastric mucosal and mucus homogenate from a cynomolgus monkey
      maintained in C57BL/6 mouse stomachs. The bacterium in the homogenate was
      identified as "Candidatus Helicobacter heilmannii" based on a DNA sequence
      analysis of the 16S rRNA and urease genes. Mucosal and mucus homogenates were
      used to inoculate C57BL/6 mice, which were then examined for 24 months. We
      observed a gradual increase in the surface area of protrusive lesions in almost
      all infected C57BL/6 mouse fundic stomachs 6 months after infection. Light
      microscopic observations revealed an accumulation of B lymphocytes along with
      destruction of glandular elements and the presence of lymphoepithelial lesions
      consistent with low-grade MALT lymphomas. Electron microscopic observation
      revealed numerous "Candidatus Helicobacter heilmannii" bacilli in the fundic
      glandular lumen, the intracellular canaliculi, and the cytoplasm of intact cells,
      as well as damaged parietal cells. In conclusion, "Candidatus Helicobacter
      heilmannii" induced gastric MALT lymphomas in almost 100% of infected C57BL/6
      mice after a 6-month period associated with the destruction of parietal cells.

PMID- 17194808
TI  - A MyD88-deficient mouse model reveals a role for Nramp1 in Campylobacter jejuni
      infection.
AB  - Campylobacter jejuni is a major worldwide cause of enteric illnesses. Adult
      immunocompetent mice are not susceptible to C. jejuni infection. However, we show
      here that mice deficient in the adaptor protein myeloid differentiation factor 88
      (MyD88), which is required for signaling through most Toll-like receptors, can be
      stably colonized by C. jejuni but not by isogenic derivatives carrying mutations
      in known virulence genes. We also found that Nramp1 deficiency increases the
      mouse susceptibility to C. jejuni infection when administered systemically. These
      results indicate that MyD88-deficient mice could be a useful model to study C.
      jejuni colonization and reveal a potential role for Nramp1 in the control of this
      bacterial pathogen.

PMID- 17194809
TI  - Analysis of the polysaccharide capsule of the systemic pathogen Streptococcus
      iniae and its implications in virulence.
AB  - Systemic pathogens have developed numerous strategies for evading the defenses of
      the host, permitting dissemination and multiplication in various tissues. One
      means of survival in the host, particularly in the bloodstream, has been
      attributed to the ability to avoid phagocytosis via capsular polysaccharide. To
      further define the virulence capacity of Streptococcus iniae, a zoonotic pathogen
      with the ability to cause severe systemic disease in both fish and humans, we
      performed an analysis of the capsule locus. The initial analysis included cloning
      and sequencing of the capsule synthesis operon, which revealed an approximately
      21-kb region that is highly homologous to capsule operons of other streptococci.
      A genetic comparison of S. iniae virulent strain 9117 and commensal strain 9066
      revealed that the commensal strain does not have the central region of the
      capsule operon composed of several important capsule synthesis genes. Four 9117
      insertion or deletion mutants with mutations in the beginning, middle, or end of
      the capsule locus were analyzed to determine their capsule production and
      virulence. Virulence profiles were analyzed for each mutant using three separate
      criteria, which demonstrated the attenuation of each mutant in several tissue
      environments. These analyses also provided insight into the different responses
      of the host to each mutant strain compared to a wild-type infection. Our results
      demonstrate that capsule is not required for all host environments, while excess
      capsule is also not optimal, suggesting that for an "ideal" systemic infection,
      capsule production is most likely regulated while the bacterium is in different
      environments of the host.

PMID- 17194811
TI  - Etiologies, environments, and genes--challenges for psychiatric diagnosis during
      an era of scientific transition.

PMID- 17194810
TI  - Experimental Fasciola hepatica infection alters responses to tests used for
      diagnosis of bovine tuberculosis.
AB  - Fasciola hepatica is a prevalent helminth parasite of livestock. Infection
      results in polarization of the host's immune response and generation of type 2
      helper (Th2) immune responses, which are known to be inhibitory to Th1 responses.
      Bovine tuberculosis (BTB) is a bacterial disease of economic and zoonotic
      importance. Control polices for this disease rely on extensive annual testing and
      a test-and-slaughter policy. The correct diagnosis of BTB relies on cell-mediated
      immune responses. We established a model of coinfection of F. hepatica and
      Mycobacterium bovis BCG to examine the impact of helminth infection on correct
      diagnosis. We found the predictive capacity of tests to be compromised in
      coinfected animals and that F. hepatica infection altered macrophage function.
      Interleukin-4 and gamma interferon expression in whole-blood lymphocytes
      restimulated in vitro with M. bovis antigen was also altered in coinfected
      animals. These results raise the question of whether F. hepatica infection can
      affect the predictive capacity of tests for the diagnosis of BTB and possibly
      also influence susceptibility to BTB and other bacterial diseases. Further
      studies on the interplay between helminth infection and BTB are warranted.

PMID- 17194812
TI  - Prevalence of International Classification of Diseases, 10th Revision common
      mental disorders in the elderly in a Brazilian community: The Bambui Health
      Ageing Study.
AB  - BACKGROUND: Most community surveys of the mental health of older people have used
      fully structured interviews administered by lay interviewers. In this study of an
      older Brazilian population, the authors investigated the prevalence and
      correlates of common mental disorders with semistructured interviews administered
      by a psychiatrist. METHOD: A two-phase population survey of 392 persons aged > or
      = 75 years were screened for depression and mental disorders using the General
      Health Questionnaire (GHQ-12) and Geriatric Depression Scale (GDS). Half of those
      scoring > or = 11 on GDS and > or = 4 on GHQ, and 20% of others, were evaluated
      in the second phase using the Schedules for Clinical Assessment in
      Neuropsychiatry (SCAN) to generate International Classification of Diseases, 10th
      Revision diagnoses. RESULTS: The prevalence of depressive episode was high
      (19.2%) with no effect of gender or age. Dysthymia is also prevalent (9.0%), but
      half of the cases were comorbid with depression. Anxiety and somatoform disorders
      were comparatively infrequent. CONCLUSIONS: Structured lay-administered
      interviews may underestimate the prevalence of mental disorders in older people.
      One month, rather than one year or lifetime, prevalence may be more appropriate
      for the oldest-old given patchy recall of distant experiences. The very strong
      association between mental disorders and poor self-reported global health
      underlines their impact on quality of life.

PMID- 17194813
TI  - Correlates of late-life major depression: a comparison of urban and rural primary
      care patients.
AB  - OBJECTIVE: The objective of this study was to determine whether factors
      associated with depression differ between elderly residents of rural and urban
      areas. METHODS: The research design was cross-sectional and observational. The
      study subjects consisted of 926 Medicare primary care patients (650 urban and 276
      rural) who were age 65+ and cognitively intact and had enrolled in a randomized,
      controlled Medicare demonstration. Major depression was identified by the Mini
      International Neuropsychiatric Interview. A logistic regression model was
      estimated that included a rural-urban indicator variable, additional independent
      variables, and interaction terms between the rural-urban indicator and
      independent variables that were significant at p <0.10. RESULTS: A total of 8.3%
      of the rural and 14.8% of the urban patients were identified as having major
      depression. Reporting 0-1 close friends (odds ratio [OR]: 6.86; 95% confidence
      interval [CI]: 2.18-21.58), 2+ emergency room visits during the past 6 months
      (OR: 4.00; 95% CI: 1.19-13.43), and more financial strain (OR: 1.50; 95% CI: 1.01
      2.23) were associated with significantly higher likelihood of major depression
      among rural as compared with urban patients. The SF-36 Physical Component Summary
      score had a curvilinear relationship with major depression and was higher for
      urban patients. The predicted probability for major depression is lower for the
      rural patients when financial strain is low, about the same for rural and urban
      patients when strain is intermediate, and higher for rural patients when strain
      is high. CONCLUSIONS: Clinicians in rural areas should be vigilant for major
      depression among patients with very few close friends, several recent emergency
      department visits, and financial strain.

PMID- 17194814
TI  - The construct of generalized anxiety disorder in Alzheimer disease.
AB  - OBJECTIVES: The objectives of this study were to examine the criterion validity
      in Alzheimer disease (AD) of Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV) and the International Classification of
      Diseases, 10th Revision (ICD-10) criteria for generalized anxiety disorder (GAD),
      to clarify the symptoms associated with excessive anxiety and worry in AD, to
      examine the co-occurrence of GAD and depression in these patients, and to
      determine the neuropsychologic and functional impact of GAD in AD. RESULTS: One
      hundred forty-four of a consecutive series of 552 patients with probable AD (26%)
      reported excessive anxiety and worry difficult to control for most of the 6
      months before the psychiatric evaluation. Excessive anxiety and worry were
      significantly associated with restlessness, irritability, muscle tension, fears,
      and respiratory symptoms of anxiety. Using these symptoms as diagnostic criteria,
      56 of the 552 patients (10%) met revised diagnostic criteria for GAD as compared
      with 15% when using DSM-IV criteria and 9% when using the ICD-10 criteria. GAD
      was present in 38 of the 144 patients (26%) with major depression and in 12 of
      the 261 patients (5%) without depression. Patients with both GAD and depression
      showed more severe cognitive deficits than patients with either GAD or depression
      only. CONCLUSION: The authors validated a set of diagnostic criteria for anxiety
      in dementia. These criteria include restlessness, irritability, muscle tension,
      fears, and respiratory symptoms in the context of excessive anxiety and worry.
      Anxiety in AD is a frequent comorbid condition of major depression.

PMID- 17194815
TI  - The effects of postoperative pain and its management on postoperative cognitive
      dysfunction.
AB  - To determine risks for postoperative cognitive dysfunction (POCD), the authors
      conducted a prospective cohort study of 225 patients > or = 65 years of age
      undergoing noncardiac surgery. Cognitive testing using the Word List, Verbal
      Fluency, and Digit Symbol tests was conducted for each patient preoperatively and
      1 and 2 days postoperatively in patients without postoperative delirium. POCD was
      defined as meeting statistical criteria for decline from the patient's
      preoperative performance levels on at least two of the three cognitive tests.
      Multivariate logistic regression analysis determined the association between pain
      and postoperative analgesia with POCD after controlling for demographics,
      comorbidities, preoperative level of cognitive and daily functioning,
      preoperative medications, duration and type of anesthesia, and adverse events.
      Patients were on average 72 years old and 13% of patients experienced POCD on day
      1, 7% on day 2, and 15% had POCD on either day 1 or day 2 after the surgery.
      Multivariate regression analyses revealed that only postoperative analgesia was
      associated with the development of POCD. Compared with those receiving
      postoperative analgesia through a patient-controlled analgesia device that
      administered opioids intravenously, those who received postoperative analgesia
      orally were at significantly lower risk for the development of POCD (odds ratio:
      0.22; 95% confidence interval: 0.06-0.80; Wald chi-square = 5.36, df = 1, p =
      0.02). Older patients undergoing noncardiac surgery who are not delirious can
      experience significant declines in cognitive functioning postoperatively. Those
      at least risk of experiencing POCD were those who received postoperative
      analgesia orally.

PMID- 17194816
TI  - Heterogeneity in risk factors for cognitive impairment, no dementia: population
      based longitudinal study from the Kungsholmen Project.
AB  - OBJECTIVES: The objectives of this study were to investigate the relation of
      vascular, neuropsychiatric, social, and frailty-related factors with "Cognitive
      impairment, no dementia" (CIND) and to verify their effect independently of
      future progression to Alzheimer disease (AD). METHODS: Seven hundred eighteen
      subjects aged 75+ years who attended baseline, 3- and 6-year follow-up
      examinations of the Kungsholmen Project, a Swedish prospective cohort study, were
      studied. CIND was defined according to the performance on the Mini-Mental State
      Examination. Potential risk factors were collected at baseline and clustered
      according to four research hypotheses (frailty, vascular, neuropsychiatric, and
      social hypothesis), each representing a possible pathophysiological mechanism of
      CIND independently of subsequent development of AD. RESULTS: Over a mean 3.4
      years of follow up, 82 participants (11.4%) developed CIND. When the population
      was subsequently followed for a mean of 2.7 years, subjects with CIND had a
      threefold increased risk to progress to AD. After multiple adjustments, including
      adjustment for the development of AD at the 6-year follow up, risk factors for
      CIND were hip fracture, polypharmacy, and psychoses. CONCLUSIONS: The results
      suggest that not only the AD-type neurodegenerative process, but also
      neuropsychiatric- and frailty-related factors may induce cognitive impairment in
      nondemented elderly. These findings may have relevant preventive and therapeutic
      implications.

PMID- 17194817
TI  - Cross-sectional association between behavioral symptoms and potential elder abuse
      among subjects in home care in Italy: results from the Silvernet Study.
AB  - OBJECTIVES: The objectives of this study were to evaluate the prevalence of
      potential elder abuse among older adults receiving home care and to assess the
      association between behavioral symptoms and potential abuse. METHODS: Data on
      4,630 subjects aged 65 or older receiving home care in Italy were collected using
      the Minimum Data Set for Home Care assessment. Potential abuse included signs of
      physical or emotional abuse and neglect. Behavioral symptoms were present if the
      participant exhibited one or more of the following symptoms in the 3 days before
      the assessment: wandering, verbally abusive, physically abusive, socially
      inappropriate behavior, and active resistance to care. RESULTS: Mean age of
      participants was 80.5 years (standard deviation: 7.7) and 2,761 (60%) were
      female. Signs of potential abuse were identified in 336 of 3,869 (9%)
      participants without behavioral symptoms and 126 of 761 (17%) with behavioral
      symptoms. After adjustment for potential confounders, presence of behavioral
      symptoms was significantly associated with potential abuse (odds ratio [OR]:
      1.56; 95% confidence interval [CI]: 1.21-2.00). Examining behavioral symptoms
      separately, wandering was negatively associated with potential abuse (OR: 0.58;
      95% CI: 0.36-0.97), whereas other symptoms were positively associated with this
      outcome (verbally abusive behavior OR: 1.69, 95% CI: 1.24-2.31; physically
      abusive behavior OR: 1.42, 95% CI: 1.00-2.03; socially inappropriate behavior OR:
      1.78, 95% CI: 1.26-2.53; active resistance of care OR: 1.69, 95% CI: 1.20-2.38).
      CONCLUSION: Signs of potential abuse are common among older adults in home care
      in Italy and they are associated with the presence of behavioral symptoms.

PMID- 17194818
TI  - Preliminary findings: behavioral worsening on donepezil in patients with
      frontotemporal dementia.
AB  - OBJECTIVE: The objective of this study was to evaluate donepezil, an
      acetylcholinesterase inhibitor, in the treatment of frontotemporal dementia
      (FTD). METHODS: Twelve patients with FTD who received donepezil for six months
      were compared with 12 FTD controls on behavioral measures. RESULTS: The groups
      did not differ on most variables at baseline or at six months; however, the
      donepezil group had greater worsening on the FTD Inventory. Four treated patients
      had increased disinhibited or compulsive acts, which abated with discontinuation
      of the medication. CONCLUSION: There were no changes in global cognitive
      performance or dementia severity; however, a subgroup of patients with FTD can
      experience worsening of symptoms with donepezil.

PMID- 17194820
TI  - Can alcohol-based hand-rub solutions cause you to lose your driver's license?
      Comparative cutaneous absorption of various alcohols.
AB  - We assessed cutaneous ethanol (ETOH) and isopropanol (ISOP) absorption after
      intensive (30 times per h) use of alcohol-based hand-rub solutions by healthcare
      workers (HCWs). ETOH was detectable in the breath of 6/20 HCWs (0.001 to 0.0025%)
      at 1 to 2 min postexposure and in the serum of 2/20 HCWs at 5 to 7 min
      postexposure. Serum ISOP levels were unrecordable at all time points.

PMID- 17194821
TI  - In vitro activities of amphotericin B, caspofungin, itraconazole, posaconazole,
      and voriconazole against 45 clinical isolates of zygomycetes: comparison of CLSI
      M38-A, Sensititre YeastOne, and the Etest.
AB  - We evaluated the activities of amphotericin B, itraconazole, voriconazole,
      caspofungin, and posaconazole against zygomycetes by CLSI M38-A, Etest and
      Sensititre. The most active drug was posaconazole, followed by amphotericin B and
      itraconazole. The correlation of the Etest and Sensititre with CLSI M38-A was
      moderate for posaconazole but poor for the others.

PMID- 17194822
TI  - Evaluation of the in vivo activity of tribendimidine against Schistosoma mansoni,
      Fasciola hepatica, Clonorchis sinensis, and Opisthorchis viverrini.
AB  - We examined the in vivo activity of tribendimidine against selected trematodes. A
      single 150-mg/kg dose of tribendimidine achieved a 99.1% reduction of Clonorchis
      sinensis in rats. A 400-mg/kg dose of tribendimidine reduced Opisthorchis
      viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity
      against Schistosoma mansoni and Fasciola hepatica.

PMID- 17194823
TI  - Orally administered erythromycin in rainbow trout (Oncorhynchus mykiss): residues
      in edible tissues and withdrawal time.
AB  - Aquaculture production has notably increased in the last decades, mainly thanks
      to intensive farming. Together with market globalization, this gives rise to the
      spreading of several fish diseases, thus increasing the demand for veterinary
      drugs for aquatic species. Nonetheless, very few chemicals are registered for use
      in aquaculture, and fish farmers are often forced to resort to off-label use of
      drugs authorized for other food-producing animal species. Rainbow trout is the
      major farmed fish species in Italy and the second one in Europe. Erythromycin is
      the antibiotic of choice against gram-positive cocci, the major concern for trout
      farming, but it is not yet registered for aquaculture use in most European
      countries. The aim of this study was to follow the depletion of erythromycin in
      rainbow trout (Oncorhynchus mykiss), after its administration at 100 mg kg(-1)
      trout body weight day(-1) for 21 days through medicated feed (water temperature,
      11.5 degrees C). Erythromycin residues in fish muscle plus skin in natural
      proportion were determined by a validated liquid chromatography-electrospray
      ionization-tandem mass spectrometry method. Interpolation of our data, following
      European Agency for the Evaluation of Medicinal Products guidelines, gives a
      withdrawal time of 255 degrees C-days ( degrees C-day = water temperature x
      days), thus showing that the general value (500 degrees C-day) recommended by the
      Council Directive (EEC) no. 82/2001 for off-label drug use in aquaculture would
      be too conservative in this case, with excessive costs for the farmers. Our study
      provides preliminary data for a more prudent use of erythromycin in rainbow
      trout, suggesting a possible withdrawal time after treatment.

PMID- 17194824
TI  - Oral versus intravenous flucytosine in patients with human immunodeficiency virus
      associated cryptococcal meningitis.
AB  - In a randomized controlled trial of amphotericin B-based therapy for human
      immunodeficiency virus (HIV)-associated cryptococcal meningitis in Thailand, we
      also compared the mycological efficacy, toxicity, and pharmacokinetics of oral
      versus intravenous flucytosine at 100 mg/kg of body weight/day for the initial 2
      weeks. Half of 32 patients assigned to the two arms containing flucytosine were
      randomized to oral and half to intravenous flucytosine. Early fungicidal activity
      was determined from serial quantitative cultures of cerebrospinal fluid (CSF),
      and toxicity was assessed by clinical and laboratory monitoring. Flucytosine and
      fluorouracil concentrations in plasma and CSF were measured by high-performance
      liquid chromatography. No significant bone marrow or hepatotoxicity was seen,
      there was no detectable difference in bone marrow toxicity between patients on
      intravenous and those on oral formulation, and no patients discontinued
      treatment. In patients receiving intravenous flucytosine, the median 24-h area
      under the concentration-time curve was significantly higher than in the oral
      group. Despite this difference, there was no difference in early fungicidal
      activity between patients on intravenous compared with patients on oral
      flucytosine. The results suggest that either formulation can be used safely at
      this dosage in a developing country setting, without drug concentration
      monitoring. The bioavailability of the oral formulation may be reduced in late
      stage HIV-infected patients in Thailand. Concentrations of flucytosine with
      intravenous formulation at 100 mg/kg/day may be in excess of those required for
      maximal fungicidal activity.

PMID- 17194825
TI  - Pretreatment with empty liposomes attenuates the immunopathology of invasive
      pulmonary aspergillosis in corticosteroid-immunosuppressed mice.
AB  - In a nonneutropenic murine model of invasive pulmonary aspergillosis,
      pretreatment with empty liposomes (E-lipo) was nearly as effective as 10 mg/kg of
      body weight liposomal amphotericin B and superior to 1 mg/kg amphotericin B
      deoxycholate. The beneficial immunomodulatory properties of E-lipo appear to
      compensate for their lack of direct antifungal activity.

PMID- 17194827
TI  - In vitro activities of tigecycline and eight other antimicrobials against
      different Nocardia species identified by molecular methods.
AB  - The in vitro activities of tigecycline and other antimicrobials against 51
      isolates of Nocardia spp. were evaluated. MIC(90)s and MIC ranges were as
      follows: tigecycline, 4 and < or =0.06 to 8 mg/liter, respectively; minocycline,
      2 and < or =0.06 to 2 mg/liter, respectively; linezolid, 1 and < or =0.06 to 2
      mg/liter, respectively; moxifloxacin, 2 and < or =0.06 to >64 mg/liter,
      respectively; ertapenem, 32 and < or =0.06->64 mg/liter, respectively; imipenem,
      2 and < or =0.06 to >64 mg/liter, respectively; meropenem, 8 and < or =0.06 to
      >64 mg/liter, respectively; amikacin, 1 and < or =0.06 to 32 mg/liter,
      respectively; and trimethoprim-sulfamethoxazole, 1/19 and < or =0.5/9.5 to >2/38
      mg/liter, respectively.

PMID- 17194826
TI  - Reversible inhibition of mitochondrial protein synthesis during linezolid-related
      hyperlactatemia.
AB  - The objective of the present study was to determine the mitochondrial toxicity
      mechanisms of linezolid-related hyperlactatemia. Five patients on a long-term
      schedule of linezolid treatment were studied during the acute phase of
      hyperlactatemia and after clinical recovery and lactate normalization following
      linezolid withdrawal. Mitochondrial studies were performed with peripheral blood
      mononuclear cells and consisted of measurement of mitochondrial mass,
      mitochondrial protein synthesis homeostasis (cytochrome c oxidase [COX] activity,
      COX-II subunit expression, COX-II mRNA abundance, and mitochondrial DNA [mtDNA]
      content), and overall mitochondrial function (mitochondrial membrane potential
      and intact-cell oxidative capacity). During linezolid-induced hyperlactatemia, we
      found extremely reduced protein expression (16% of the remaining content compared
      to control values [100%], P < 0.001) for the mitochondrially coded, transcribed,
      and translated COX-II subunit. Accordingly, COX activity was also found to be
      decreased (51% of the remaining activity, P < 0.05). These reductions were
      observed despite the numbers of COX-II mitochondrial RNA transcripts being
      abnormally increased (297%, P = 0.10 [not significant]) and the mitochondrial DNA
      content remaining stable. These abnormalities persisted even after the correction
      for mitochondrial mass, which was mildly decreased during the hyperlactatemic
      phase. Most of the mitochondrial abnormalities returned to control ranges after
      linezolid withdrawal, lactate normalization, and clinical recovery. Linezolid
      inhibits mitochondrial protein synthesis, leading to decreased mitochondrial
      enzymatic activity, which causes linezolid-related hyperlactatemia, which
      resolves upon discontinuation of linezolid treatment.

PMID- 17194828
TI  - The beta-defensin gallinacin-6 is expressed in the chicken digestive tract and
      has antimicrobial activity against food-borne pathogens.
AB  - Food-borne pathogens are responsible for most cases of food poisoning in
      developed countries and are often associated with poultry products, including
      chicken. Little is known about the role of beta-defensins in the chicken
      digestive tract and their efficacy. In this study, the expression of chicken beta
      defensin gallinacin-6 (Gal-6) and its antimicrobial activity against food-borne
      pathogens were investigated. Reverse transcription-PCR analysis showed high
      expression of Gal-6 mRNA in the esophagus and crop, moderate expression in the
      glandular stomach, and low expression throughout the intestinal tract. Putative
      transcription factor binding sites for nuclear factor kappa beta, activator
      protein 1, and nuclear factor interleukin-6 were found in the Gal-6 gene upstream
      region, which suggests a possible inducible nature of the Gal-6 gene. In colony
      counting assays, strong bactericidal and fungicidal activity was observed,
      including bactericidal activity against food-borne pathogens Campylobacter
      jejuni, Salmonella enterica serovar Typhimurium, Clostridium perfringens, and
      Escherichia coli. Treatment with 16 mug/ml synthetic Gal-6 resulted in a 3 log
      unit reduction in Clostridium perfringens survival within 60 min, indicating fast
      killing kinetics. Transmission electron microscopy examination of synthetic-Gal-6
      treated Clostridium perfringens cells showed dose-dependent changes in morphology
      after 30 min, including intracellular granulation, cytoplasm retraction,
      irregular septum formation in dividing cells, and cell lysis. The high expression
      in the proximal digestive tract and broad antimicrobial activity suggest that
      chicken beta-defensin gallinacin-6 plays an important role in chicken innate host
      defense.

PMID- 17194829
TI  - Impact of empiric antibiotic therapy on outcomes in patients with Pseudomonas
      aeruginosa bacteremia.
AB  - The impact of appropriate empirical antimicrobial therapy for Pseudomonas
      aeruginosa bacteremia on patient outcomes has not been clearly established. We
      assessed the effect of appropriate empirical therapy on in-hospital mortality and
      length of stay (LOS) among patients with P. aeruginosa bacteremia. This was a
      retrospective cohort study of inpatients with a positive blood culture for P.
      aeruginosa between January 2001 and June 2005. Empirical therapy was defined as
      appropriate if the patient received an antibiotic the organism was susceptible to
      between 8 h before culture collection and the time the susceptibility results
      were available. The severity of the illness was measured 24 h before culture
      collection. The data were analyzed using logistic regression (in-hospital
      mortality) and linear regression (LOS). Overall, there were 167 episodes of P.
      aeruginosa bacteremia, 123 (86%) of which received appropriate empirical
      antibiotics. Sixty-one patients died (36.5%). The median time from culture
      collection to susceptibility results was 3.4 days. After we adjusted for age,
      severity of illness, and time at risk, we found that the appropriate empirical
      therapy was not significantly associated with mortality (odds ratio = 0.96; 95%
      confidence interval = 0.31 to 2.93). There was a 7% reduction in the mean LOS for
      patients who had received appropriate therapy at the time susceptibility results
      were available compared to those who did not (P = 0.74). These data suggest that
      the use of appropriate empirical therapy, i.e., before susceptibility results are
      known may not be as critical to patient outcomes as other studies have suggested.

PMID- 17194830
TI  - Once-weekly micafungin therapy is as effective as daily therapy for disseminated
      candidiasis in mice with persistent neutropenia.
AB  - The effect of micafungin dose scheduling on the treatment of candidemia is
      unknown. Neutropenic mice with disseminated Candida glabrata infection were
      treated with single intraperitoneal micafungin doses of 0 to 100 mg/kg of body
      weight and sacrificed 7 days later. The maximal decline in kidney fungal burden
      was 5.8 log(10) CFU/g. A 1-week pharmacokinetic-pharmacodynamic study revealed a
      micafungin serum half-life of 6.13 h. In mice treated with > or =50 mg/kg, there
      was maximal fungal decline without regrowth during the 1-week dosing interval.
      Next, doses associated with 34% (34% effective dose [ED(34)]) and 50% (ED(50)) of
      maximal kill were administered at one of three dose schedules: a single dose at t
      = 0, two equal doses at t = 0 and t = 3.5 days, and 7 equal doses daily. Some
      mice received a single dose of 100 mg/kg. Fungal burden was examined on days 1,
      5, and 7. In mice treated with the ED(34), microbial kill with the daily therapy
      initially lagged behind the intermittent doses but exceeded it by day 7. In mice
      treated with the ED(50), daily and intermittent doses had equivalent day 7
      effects. In mice treated with 100 mg/kg, there was no regrowth. The relative
      likelihoods that the area under the concentration-time curve/MIC ratio was linked
      to microbial kill versus peak concentration/MIC ratio or time above the MIC was
      10.3 and 10,161.2, respectively. In all the experiments, no paradoxical increase
      in fungal burden was observed with high micafungin doses. However, only a single
      Candida isolate was tested. Regimens that simulated micafungin concentration-time
      profiles in patients treated with a single micafungin dose of 1,400 mg once a
      week demonstrated maximal fungal decline. Once-weekly micafungin therapy is as
      efficacious as daily therapy in a murine model of disseminated candidiasis.

PMID- 17194831
TI  - Flavonoid dimers as bivalent modulators for pentamidine and sodium stiboglucanate
      resistance in leishmania.
AB  - Drug resistance by overexpression of ATP-binding cassette (ABC) transporters is
      an impediment in the treatment of leishmaniasis. Flavonoids are known to reverse
      multidrug resistance (MDR) in Leishmania and mammalian cancers by inhibiting ABC
      transporters. Here, we found that synthetic flavonoid dimers with three (compound
      9c) or four (compound 9d) ethylene glycol units exhibited a significantly higher
      reversing activity than other shorter or longer ethylene glycol-ligated dimers,
      with approximately 3-fold sensitization of pentamidine and sodium stibogluconate
      (SSG) resistance in Leishmania, respectively. This modulatory effect was dosage
      dependent and not observed in apigenin monomers with the linker, suggesting that
      the modulatory effect is due to its bivalent nature. The mechanism of reversal
      activity was due to increased intracellular accumulation of pentamidine and total
      antimony in Leishmania. Compared to other MDR modulators such as verapamil,
      reserpine, quinine, quinacrine, and quinidine, compounds 9c and 9d were the only
      agents that can reverse SSG resistance. In terms of reversing pentamidine
      resistance, 9c and 9d have activities comparable to those of reserpine and
      quinacrine. Modulators 9c and 9d exhibited reversal activity on pentamidine
      resistance among LeMDR1(-/-), LeMDR1(+/+), and LeMDR1-overexpressed mutants,
      suggesting that these modulators are specific to a non-LeMDR1 pentamidine
      transporter. The LeMDR1 copy number is inversely related to pentamidine
      resistance, suggesting that it might be involved in importing pentamidine into
      the mitochondria. In summary, bivalency could be a useful strategy for the
      development of more potent ABC transporter modulators and flavonoid dimers
      represent a promising reversal agent for overcoming pentamidine and SSG
      resistance in parasite Leishmania.

PMID- 17194832
TI  - Efficacy of orally administered T-705 on lethal avian influenza A (H5N1) virus
      infections in mice.
AB  - T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) was inhibitory to four strains
      of avian H5N1 influenza virus in MDCK cells, with the 90% effective
      concentrations ranging from 1.3 to 7.7 microM, as determined by a virus yield
      reduction assay. The efficacy was less than that exerted by oseltamivir
      carboxylate or zanamivir but was greater than that exerted by ribavirin.
      Experiments with mice lethally infected with influenza A/Duck/MN/1525/81 (H5N1)
      virus showed that T-705 administered per os once, twice, or four times daily for
      5 days beginning 1 h after virus exposure was highly inhibitory to the infection.
      Dosages from 30 to 300 mg/kg of body weight/day were well tolerated; each
      prevented death, lessened the decline of arterial oxygen saturation (SaO(2)), and
      inhibited lung consolidation and lung virus titers. Dosages from 30 to 300
      mg/kg/day administered once or twice daily also significantly prevented the death
      of the mice. Oseltamivir (20 mg/kg/day), administered per os twice daily for 5
      days, was tested in parallel in two experiments; it was only weakly effective
      against the infection. The four-times-daily T-705 treatments at 300 mg/kg/day
      could be delayed until 96 h after virus exposure and still significantly inhibit
      the infection. Single T-705 treatments administered up to 60 h after virus
      exposure also prevented death and the decline of SaO(2). Characterization of the
      pathogenesis of the duck influenza H5N1 virus used in these studies was
      undertaken; although the virus was highly pathogenic to mice, it was less
      neurotropic than has been described for clinical isolates of the H5N1 virus.
      These data indicate that T-705 may be useful for the treatment of avian influenza
      virus infections.

PMID- 17194833
TI  - Similar trends of pyrimethamine resistance-associated mutations in Plasmodium
      vivax and P. falciparum.
AB  - The antifolate drugs sulfadoxine and pyrimethamine are commonly used to treat
      Plasmodium falciparum malaria. However, they can also affect the Plasmodium vivax
      parasite if it coexists with P. falciparum, as both species have common drug
      targets. Resistance to the antifolate drugs arises due to point mutations in the
      target enzymes of the respective parasite. To assess the cross-species impact of
      antifolate drug treatment, we describe here the dihydrofolate reductase (DHFR)
      mutations among field isolates of P. vivax and P. falciparum. The overall DHFR
      mutation rate for P. vivax was lower than that for P. falciparum. However, both
      species of Plasmodium followed similar trends of DHFR mutations. Similar to P.
      falciparum, the DHFR mutation rate of P. vivax also varied from region to region.
      It was lower in P. vivax-dominant regions but higher in the P. falciparum
      dominated areas and highest where antifolates are used as the first line of
      antimalarial treatment. In conclusion, the antifolate treatment of falciparum
      malaria is proportionately affecting the DHFR mutations of P. vivax, suggesting
      that the drug should be used with caution to minimize the development of cross
      species resistance in the field.

PMID- 17194834
TI  - Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium
      falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria.
AB  - The artemisinin-based combination therapies artemether-lumefantrine (AL) and
      amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium
      falciparum malaria in many African countries. Molecular markers of parasite
      resistance suitable for surveillance have not been established for any of the
      component drugs in either of these combinations. We assessed P. falciparum mdr1
      (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated
      falciparum malaria, who were enrolled in a clinical trial of antimalarial
      therapy. Pfmdr1 genotype analysis was also performed with isolates from 182
      children who failed AQ monotherapy and 54 children who failed AL treatment.
      Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in
      the AQ group than among pretreatment infections. The converse was found in the AL
      treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and
      treated with AQ were significantly more likely to retain this haplotype if they
      were parasite positive during posttreatment follow-up than were children treated
      with AL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, <0.001). We
      conclude that AL and AQ exert opposite within-host selective effects on the
      Pfmdr1 gene of P. falciparum.

PMID- 17194835
TI  - Cumulative effects of several nonenzymatic mechanisms on the resistance of
      Pseudomonas aeruginosa to aminoglycosides.
AB  - Screening of a Tn5-Hg insertional library (12,000 clones) constructed in wild
      type Pseudomonas aeruginosa strain PAO1 identified four genes (namely, galU,
      nuoG, mexZ, and rplY) whose disruption individually led to increased resistance
      to aminoglycosides (means of twofold). Inactivation of these genes was associated
      with (i) impaired outer membrane uptake, (ii) reduced active transport, (iii)
      increased MexXY-OprM-mediated active efflux, and (iv) alteration of target of
      aminoglycosides, respectively. In addition, suppression of the gene rplY, which
      codes for ribosomal protein L25, was found to result in both moderate
      upregulation of the efflux system MexXY-OprM and hypersusceptibility to beta
      lactam antibiotics. Construction of double, triple, and quadruple mutants
      demonstrated cumulative effects of the different mechanisms on aminoglycoside
      resistance, with MICs increasing from 16- to 64-fold in the quadruple mutant
      compared to the wild-type strain PAO1. Altogether, these results illustrate how
      P. aeruginosa may gradually develop high resistance to these antibiotics via
      intrinsic (i.e., nonenzymatic) mechanisms, as in cystic fibrosis patients.

PMID- 17194836
TI  - PCR-based detection of Angiostrongylus cantonensis in tissue and mucus secretions
      from molluscan hosts.
AB  - Angiostrongylus cantonensis is a common cause of human eosinophilic meningitis.
      Recent outbreaks of this infection have shown that there is a need to determine
      the distribution of this nematode in the environment in order to control
      transmission. A. cantonensis is generally identified morphologically in the
      molluscan intermediate host by microscopic examination, which can be labor
      intensive. The aim of this study was to develop a PCR-based method to detect A.
      cantonensis directly from molluscan tissue. A total of 34 Parmarion cf. martensi
      (Simroth) semislugs, 25 of which were naturally infected with A. cantonensis,
      were used to develop this assay. Tissue pieces (approximately 25 mg) were
      digested with pepsin-HCl to recover third-stage larvae for morphological
      identification or were used for DNA extraction. PCR primers were designed to
      amplify 1,134 bp from the Angiostrongylus 18S rRNA gene, and the amplicons
      produced were sequenced for identification at the species level. Both microscopy
      and the PCR-DNA sequencing analysis indicated that the same 25 semislugs were
      positive for A. cantonensis, showing that the two methods were equally sensitive
      and specific for this application. However, morphological detection requires
      access to living mollusks, whereas molecular analysis can also be performed with
      frozen tissue. The PCR-DNA sequencing method was further evaluated using tissue
      from Veronicella cubensis (Pfeiffer) slugs and mucus secretions from infected P.
      martensi. To our knowledge, this is the first use of a PCR-based method to
      confirm the presence of A. cantonensis in mollusks collected in the environment.

PMID- 17194838
TI  - Salivaricin A2 and the novel lantibiotic salivaricin B are encoded at adjacent
      loci on a 190-kilobase transmissible megaplasmid in the oral probiotic strain
      Streptococcus salivarius K12.
AB  - The commercial probiotic Streptococcus salivarius strain K12 is the prototype of
      those S. salivarius strains that are the most strongly inhibitory in a
      standardized test of streptococcal bacteriocin production and has been shown to
      produce the 2,368-Da salivaricin A2 (SalA2) and the 2,740-Da salivaricin B (SboB)
      lantibiotics. The previously uncharacterized SboB belongs to the type AII class
      of lantibiotic bacteriocins and is encoded by an eight-gene cluster. The genetic
      loci encoding SalA2 and SboB in strain K12 have been fully characterized and are
      localized to nearly adjacent sites on pSsal-K12, a 190-kb megaplasmid. Of 61
      strongly inhibitory strains of S. salivarius, 19 (31%) were positive for the sboB
      structural gene. All but one (strain NR) of these 19 strains were also positive
      for salA2, and in each of these cases of double positivity, the two loci were
      separated by fewer than 10 kb. This is the first report of a single streptococcus
      strain producing two distinct lantibiotics.

PMID- 17194837
TI  - Characterization of environmental sources of the human and animal pathogen
      Cryptococcus gattii in British Columbia, Canada, and the Pacific Northwest of the
      United States.
AB  - Cryptococcus gattii has recently emerged as a primary pathogen of humans and wild
      and domesticated animals in British Columbia, particularly on Vancouver Island.
      C. gattii infections are typically infections of the pulmonary and/or the central
      nervous system, and the incidence of infection in British Columbia is currently
      the highest reported globally. Prior to this emergence, the environmental
      distribution of and the extent of colonization by C. gattii in British Columbia
      were unknown. We characterized the environmental sources and potential
      determinants of colonization in British Columbia. C. gattii was isolated from
      tree surfaces, soil, air, freshwater, and seawater, and no seasonal prevalence
      was observed. The C. gattii concentrations in air samples were significantly
      higher during the warm, dry summer months, although potentially infectious
      propagules (<3.3 microm in diameter) were present throughout the year. Positive
      samples were obtained from many different areas of British Columbia, and some
      locations were colonization "hot spots." C. gattii was generally isolated from
      acidic soil, and geographic differences in soil pH may influence the extent of
      colonization. C. gattii soil colonization also was associated with low moisture
      and low organic carbon contents. Most of the C. gattii isolates recovered
      belonged to the VGIIa genetic subtype; however, sympatric colonization by the
      VGIIb strain was observed at most locations. At one sampling site, VGIIa, VGIIb,
      VGI, and the Cryptococcus neoformans serotype AD hybrid all were coisolated. Our
      findings indicate extensive colonization by C. gattii within British Columbia and
      highlight an expansion of the ecological niche of this pathogen.

PMID- 17194839
TI  - Persistence, transmission, and virulence characteristics of Aeromonas strains in
      a duckweed aquaculture-based hospital sewage water recycling plant in Bangladesh.
AB  - The persistence and transmission of Aeromonas in a duckweed aquaculture-based
      hospital sewage water treatment plant in Bangladesh was studied. A total of 670
      samples from different sites of the hospital sewage water treatment plant, from
      feces of hospitalized children suffering from diarrhea, from environmental
      control ponds, and from feces of healthy humans were collected over a period of
      three years. In total, 1,315 presumptive Aeromonas isolates were biochemically
      typed by the PhenePlate rapid screening system (PhP-AE). A selection of 90
      representative isolates was further analyzed with PhenePlate (PhP) extended
      typing (PhP-48), fatty acid methyl ester analysis, and amplified fragment length
      polymorphism (AFLP) fingerprinting. In addition, the prevalence of the putative
      virulence factors hemolysin and cytotoxin and the presence of the cytolytic
      enterotoxin gene (AHCYTOEN) were analyzed. Aeromonas was found at all sites of
      the treatment plant, in 40% of the samples from environmental control ponds, in
      8.5% of the samples from hospitalized children suffering from diarrhea, and in
      3.5% of samples from healthy humans. A significantly high number of Aeromonas
      bacteria was found in duckweed, which indicates that duckweed may serve as a
      reservoir for these bacteria. PhP-AE typing allowed identification of more than
      192 distinct PhP types, of which 18 major PhP types (MTs) were found in multiple
      sites and during several occasions. AFLP fingerprinting revealed the prevalence
      of genotypically indistinguishable Aeromonas isolates among certain PhP MTs
      recovered from different sampling occasions and/or at multiple sites. Hemolytic
      and cytotoxic activities were observed in 43% of the tested strains, whereas 29%
      possessed the cytolytic enterotoxin gene AHCYTOEN. Collectively, two specific MTs
      associated with diarrhea were shown to exhibit high cytotoxicity. Furthermore,
      all tested isolates of these major types were positive for the cytolytic
      enterotoxin gene. In conclusion, our data indicate that certain phenotypically
      and genotypically stable clonal lineages of Aeromonas have persisted in the
      treatment system for a prolonged period and might spread from the hospitalized
      children suffering from diarrhea to fish produced for human consumption through
      the sewage water treatment system.

PMID- 17194840
TI  - Integrated real-time PCR for detection and monitoring of Legionella pneumophila
      in water systems.
AB  - We evaluated a ready-to-use real-time quantitative Legionella pneumophila PCR
      assay system by testing 136 hot-water-system samples collected from 55 sites as
      well as 49 cooling tower samples collected from 20 different sites, in parallel
      with the standard culture method. The PCR assay was reproducible and suitable for
      routine quantification of L. pneumophila. An acceptable correlation between PCR
      and culture results was obtained for sanitary hot-water samples but not for
      cooling tower samples. We also monitored the same L. pneumophila-contaminated
      cooling tower for 13 months by analyzing 104 serial samples. The culture and PCR
      results were extremely variable over time, but the curves were similar. The
      differences between the PCR and culture results did not change over time and were
      not affected by regular biocide treatment. This ready-to-use PCR assay for L.
      pneumophila quantification could permit more timely disinfection of cooling
      towers.

PMID- 17194841
TI  - Circumventing the effect of product toxicity: development of a novel two-stage
      production process for the lantibiotic gallidermin.
AB  - Lantibiotics such as gallidermin are lanthionine-containing polypeptide
      antibiotics produced by gram-positive bacteria that might become relevant for the
      treatment of various infectious diseases. So far, self-toxicity has prevented the
      isolation of efficient overproducing strains, thus hampering their thorough
      investigation and preventing their exploitation in fields other than the food
      area. We wanted to investigate the effect of lantibiotic precursor peptides on
      the producing strains in order to evaluate novel strategies for the
      overproduction of these promising peptides. In this study, gallidermin was chosen
      as a representative example of the type A lantibiotics. A Staphylococcus
      gallinarum Tu3928 mutant, whose gene for the extracellular pregallidermin
      protease GdmP was replaced by a kanamycin-resistance gene, was constructed. Mass
      spectrometry (MS) analysis indicated that this mutant produced fully
      posttranslationally modified gallidermin precursors with truncated versions of
      the leader peptide, but not the entire leader as predicted from the gdmA
      sequence. In filter-on-plate assays, these truncated pregallidermins showed no
      toxicity against Staphylococcus gallinarum Tu3928 up to a concentration of 8
      g/liter (corresponding to approximately 2.35 mM), while gallidermin produced
      clear inhibitory zones at concentrations as low as 0.25 g/liter (0.12 mM). We
      showed that the lack of toxicity is due entirely to the presence of the truncated
      leader, since MS as well as bioassay analysis showed that the peptides resulting
      from tryptic cleavage of pregallidermins and gallidermin produced by S.
      gallinarum Tu3928 had identical masses and approximately the same specific
      activity. This demonstrates that even a shortened leader sequence is sufficient
      to prevent the toxicity of mature gallidermin. In nonoptimized fermentations, the
      gdmP mutant produced pregallidermin to a 50%-higher molar titer, suggesting that
      the absence of self-toxicity has a beneficial effect on gallidermin production
      and giving a first confirmation of the suitability of the overproduction
      strategy.

PMID- 17194842
TI  - Metabolic engineering of carotenoid biosynthesis in Escherichia coli by ordered
      gene assembly in Bacillus subtilis.
AB  - We attempted to optimize the production of zeaxanthin in Escherichia coli by
      reordering five biosynthetic genes in the natural carotenoid cluster of Pantoea
      ananatis. Newly designed operons for zeaxanthin production were constructed by
      the ordered gene assembly in Bacillus subtilis (OGAB) method, which can assemble
      multiple genes in one step using an intrinsic B. subtilis plasmid transformation
      system. The highest level of production of zeaxanthin in E. coli (820 microg/g
      [dry weight]) was observed in the transformant with a plasmid in which the gene
      order corresponds to the order of the zeaxanthin metabolic pathway (crtE-crtB
      crtI-crtY-crtZ), among a series of plasmids with circularly permuted gene orders.
      Although two of five operons using intrinsic zeaxanthin promoters failed to
      assemble in B. subtilis, the full set of operons was obtained by repressing
      operon expression during OGAB assembly with a p(R) promoter-cI repressor system.
      This result suggests that repressing the expression of foreign genes in B.
      subtilis is important for their assembly by the OGAB method. For all tested
      operons, the abundance of mRNA decreased monotonically with the increasing
      distance of the gene from the promoter in E. coli, and this may influence the
      yield of zeaxanthin. Our results suggest that rearrangement of biosynthetic genes
      in the order of the metabolic pathway by the OGAB method could be a useful
      approach for metabolic engineering.

PMID- 17194843
TI  - Impact of antimicrobial usage on antimicrobial resistance in commensal
      Escherichia coli strains colonizing broiler chickens.
AB  - Escherichia coli strains isolated from commercial broilers and an experimental
      flock of chickens were screened to determine phenotypic expression of
      antimicrobial resistance and carriage of drug resistance determinants. The goal
      of this study was to investigate the influence of oxytetracycline, sarafloxacin,
      and enrofloxacin administration on the distribution of resistance determinants
      and strain types among intestinal commensal E. coli strains isolated from broiler
      chickens. We detected a high prevalence of resistance to drugs such as
      tetracycline (36 to 97%), sulfonamides (50 to 100%), and streptomycin (53 to
      100%) in E. coli isolates from treated and untreated flocks. These isolates also
      had a high prevalence of class 1 integron carriage, and most of them possessed
      the streptomycin resistance cassette, aadA1. In order to investigate the
      contribution of E. coli strain distribution to the prevalence of antimicrobial
      resistance and the resistance determinants, isolates from each flock were DNA
      fingerprinted by enterobacterial repetitive intergenic consensus sequence (ERIC)
      PCR. Although very diverse E. coli strain types were detected, four ERIC strain
      types were present on all of the commercial broiler farms, and two of the strains
      were also found in the experimental flocks. Each E. coli strain consisted of both
      susceptible and antimicrobial agent-resistant isolates. In some instances,
      isolates of the same E. coli strain expressed the same drug resistance patterns
      although they harbored different tet determinants or streptomycin resistance
      genes. Therefore, drug resistance patterns could not be explained solely by
      strain prevalence, indicating that mobile elements contributed significantly to
      the prevalence of resistance.

PMID- 17194846
TI  - Visual constructive and visual-motor skills in deaf native signers.
AB  - Visual constructive and visual-motor skills in the deaf population were
      investigated by comparing performance of deaf native signers (n=20) to that of
      hearing nonsigners (n=20) on the Beery-Buktenica Developmental Test of Visual
      Motor Integration, Rey-Osterrieth Complex Figure Test, Wechsler Memory Scale
      Visual Reproduction subtest, and Stanford-Binet Intelligence Scale Paper Folding
      and Cutting subtest. Deaf signers were found to perform similarly to hearing
      controls, suggesting that these tests are valid assessment instruments to use
      with deaf individuals.

PMID- 17194844
TI  - Amino acid substitutions in GyrA of Burkholderia glumae are implicated in not
      only oxolinic acid resistance but also fitness on rice plants.
AB  - Oxolinic acid (OA) resistance in field isolates of Burkholderia glumae, a causal
      agent of bacterial grain rot, is dependent on an amino acid substitution at
      position 83 in GyrA (GyrA83). In the present study, among spontaneous in vitro
      mutants from the OA-sensitive B. glumae strain Pg-10, we selected OA-resistant
      mutants that emerged at a rate of 5.7 x 10(-10). Nucleotide sequence analysis of
      the quinolone resistance-determining region in GyrA showed that Gly81Cys,
      Gly81Asp, Asp82Gly, Ser83Arg, Asp87Gly, and Asp87Asn are observed in these OA
      resistant mutants. The introduction of each amino acid substitution into Pg-10
      resulted in OA resistance, similar to what was observed for mutants with the
      responsible amino acid substitution. In vitro growth of recombinants with
      Asp82Gly was delayed significantly compared to that of Pg-10; however, that of
      the other recombinants did not differ significantly. The inoculation of each
      recombinant into rice spikelets did not result in disease. In inoculated rice
      spikelets, recombinants with Ser83Arg grew less than Pg-10 during flowering, and
      growth of the other recombinants was reduced significantly. On the other hand,
      the reduced growth of recombinants with Ser83Arg in spikelets was compensated for
      under OA treatment, resulting in disease. These results suggest that amino acid
      substitutions in GyrA of B. glumae are implicated in not only OA resistance but
      also fitness on rice plants. Therefore, GyrA83 substitution is thought to be
      responsible for OA resistance in B. glumae field isolates.

PMID- 17194848
TI  - The polio epidemic in Israel in the 1950s.

PMID- 17194847
TI  - Alliance for cervical cancer prevention: setting the record straight.

PMID- 17194849
TI  - Allan Rosenfield: public health's noble soul with a big heart.

PMID- 17194850
TI  - Reconsidering the feasibility of papanicolaou and alternative screening tests for
      low-resource countries.

PMID- 17194851
TI  - Reducing the ethnic disparities in food access.

PMID- 17194852
TI  - Tobacco and alcohol advertising in televised sports: time to focus on policy
      change.

PMID- 17194853
TI  - Long-term reductions in mortality among children under age 5 in rural Haiti:
      effects of a comprehensive health system in an impoverished setting.
AB  - OBJECTIVES: Evidence regarding the long-term impact of health and other community
      development programs on under-5 mortality (the risk of death from birth until the
      fifth birthday) is limited. We compared mortality in a population served by
      health and other community development programs at the Hopital Albert Schweitzer
      (HAS) with national mortality rates among children younger than 5 years for Haiti
      between 1958 and 1999. METHODS: We collected information on births and deaths in
      the HAS service area between 1995 and 1999 and assembled previously published
      under-5 mortality rates at HAS. Published national rates for Haiti served as a
      comparison. RESULTS: In the early 1970s, the under-5 mortality rate at HAS
      declined to a level three fourths lower than that in Haiti nationwide. More
      recently, HAS rates have remained at one half those for Haiti nationwide. Child
      survival interventions in the HAS service area were substantially higher than in
      Haiti nationwide although socioeconomic characteristics and levels of childhood
      malnutrition were similar in both areas. CONCLUSIONS: HAS's programs have been
      responsible for long-term sustained reduction in mortality among children aged
      less than 5 years. Integrated systems for health and other community development
      programs could be an effective strategy for achieving the United Nations
      Millennium Goal to reduce under-5 mortality two thirds by 2015.

PMID- 17194854
TI  - Association between adult and childhood socioeconomic status and prevalence of
      the metabolic syndrome in African Americans: the Pitt County Study.
AB  - We evaluated the association between socioeconomic status (SES) during childhood
      and adulthood and prevalence of the metabolic syndrome in African Americans.
      Higher adult educational status and adult skilled occupation were protective
      against the metabolic syndrome, but no associations were found between the
      metabolic syndrome and other SES variables. Differences by gender were observed.
      Improving access to education among African Americans could reduce risk for the
      metabolic syndrome, but more research is needed in minority populations.

PMID- 17194855
TI  - Current priorities in health research funding and lack of impact on the number of
      child deaths per year.
AB  - We determined the proportion of research on childhood mortality directed toward
      better medical technology (i.e., by improving old technology or creating new
      technology) compared with research on technology delivery and utilization. We
      also estimated mortality reductions from a research-funding strategy focusing
      primarily on developing technology compared with one that also focused on
      delivery and utilization. Ninety-seven percent of grants were for developing new
      technologies, which could reduce child mortality by 22%. This reduction is one
      third of what could be achieved if existing technologies were fully utilized.
      There is a serious discrepancy between current research and the research needed
      to save children's lives. In addition to increased research on the efficacy of
      treatment, there is an even greater need for increased research on delivery and
      use of technology.

PMID- 17194856
TI  - Paternalism and its discontents: motorcycle helmet laws, libertarian values, and
      public health.
AB  - The history of motorcycle helmet legislation in the United States reflects the
      extent to which concerns about individual liberties have shaped the public health
      debate. Despite overwhelming epidemiological evidence that motorcycle helmet laws
      reduce fatalities and serious injuries, only 20 states currently require all
      riders to wear helmets. During the past 3 decades, federal government efforts to
      push states toward enactment of universal helmet laws have faltered, and
      motorcyclists' advocacy groups have been successful at repealing state helmet
      laws. This history raises questions about the possibilities for articulating an
      ethics of public health that would call upon government to protect citizens from
      their own choices that result in needless morbidity and suffering.

PMID- 17194857
TI  - Racial and ethnic differentials in overweight and obesity among 3-year-old
      children.
AB  - OBJECTIVES: We estimated racial/ethnic differences in overweight and obesity in a
      national sample of 3-year-olds from urban, low-income families and assessed
      possible determinants of differences. METHODS: Survey, in-home observation, and
      interview data were collected at birth, 1 year, and 3 years. We used logistic
      regression analyses and adjusted for a range of covariates in examining
      overweight and obesity differentials according to race/ethnicity. RESULTS: Thirty
      five percent of the study children were overweight or obese. Hispanic children
      were twice as likely as either Black or White children to be overweight or obese.
      Although we controlled for a wide variety of characteristics, we were unable to
      explain either White-Hispanic or Black-Hispanic differences in overweight and
      obesity. However, birthweight, taking a bottle to bed, and mother's weight status
      were important predictors of children's overweight or obesity at age 3 years.
      CONCLUSIONS: Children's problems with overweight and obesity begin as early as
      age 3, and Hispanic children and those with obese mothers are especially at risk.

PMID- 17194858
TI  - Time spent outdoors at midday and children's body mass index.
AB  - OBJECTIVES: We investigated whether the Kidskin sun protection intervention
      increased children's body mass index by reducing the time spent outdoors at
      midday. METHODS: The Kidskin sun protection intervention involved 1614 Australian
      school children assigned to 1 of 3 groups: a control group, a moderate
      intervention group, or a high-intervention group. Schools in the control group
      received the standard health curriculum and schools in the intervention groups
      received a multicomponent intervention. Outcomes included time spent outdoors and
      nevus development (a marker of melanoma risk). Height and weight were measured at
      3 time points. Body mass index was transformed into age- and gender-specific z
      scores; z scores at each age were modeled simultaneously. Time spent outdoors at
      ages 10 and 12 years was analyzed using a linear mixed effects modeling. RESULTS:
      The proportion of children who were overweight or obese increased with age. The
      moderate-intervention and control groups had a minimal increase in z score over
      time, and the z score for the high-intervention group decreased over time. There
      were no differences among groups with respect to total time outdoors at any age.
      CONCLUSIONS: It is possible to reduce the time children spend outdoors when
      ultraviolet radiation is high without producing an unfavorable effect on the
      children's body mass index.

PMID- 17194859
TI  - Associations between childhood intelligence and hospital admissions for
      unintentional injuries in adulthood: the Aberdeen Children of the 1950s cohort
      study.
AB  - OBJECTIVES: We examined associations between childhood intelligence and hospital
      admissions for injuries in adulthood. METHODS: Data were derived from a cohort
      study (=11103) involving individuals born in Aberdeen, Scotland, between 1950 and
      1956. RESULTS: Overall, 1043 cohort members had at least 1 hospital admission
      resulting from an unintentional injury over 231152 person-years of risk. There
      were inverse linear associations between childhood intelligence assessed at the
      ages of 7, 9, and 11 years and having had a hospital admission stemming from an
      unintentional injury (gender-adjusted hazard ratio [HR] for a 1-standard
      deviation increase in intelligence test score at age 7 years = 0.75; 95%
      confidence interval [CI]=0.70, 0.80). These associations were not markedly
      affected by adjustment for childhood socioeconomic status, maternal age or
      height, birthweight, or childhood growth. However, they were attenuated after
      adjustment for educational attainment (HR=0.85; 95% CI=0.78, 0.91). CONCLUSIONS:
      Childhood intelligence is related to hospital admissions for injuries in
      adulthood, and this relationship is partly explained by educational attainment.
      The association between childhood intelligence and injury may contribute to the
      association between childhood intelligence and premature mortality demonstrated
      in several studies.

PMID- 17194860
TI  - Changing the child labor laws for agriculture: impact on injury.
AB  - OBJECTIVE: The child labor laws are intended to protect young workers from the
      most dangerous jobs. However, children who work on their parents' farms are
      exempt from these laws. We evaluated the potential for preventing the occurrence
      of farm injuries among children by changing the US Federal Child Labor Laws,
      Hazardous Occupations Orders for Agriculture. METHODS: A retrospective case
      series of 1193 farm injuries among children from the United States and Canada was
      assembled. The Hazardous Occupations Orders were systematically applied to each
      case. Injury preventability was estimated. RESULTS: A total of 286 (24%) cases of
      injury involved immediate family members engaged in farm work. Among these
      children, 33% of those aged younger than 16 years and 36% of those aged 16 or 17
      years were performing work prohibited under the Hazardous Occupations Orders.
      CONCLUSIONS: Removing the family farm exemption from the Hazardous Occupations
      Orders and raising the age restriction for performing hazardous agricultural work
      from 16 to 18 years would be efficacious in preventing the most serious injuries
      experienced by young family farm workers. Potential reductions in injury would
      meet Healthy People 2010 goals for reducing traumatic injury in the agricultural
      sector.

PMID- 17194861
TI  - Anemia and iron deficiency in school children, adolescents, and adults: a
      community-based study in rural Amazonia.
AB  - We investigated the prevalence and risk factors of anemia and iron deficiency in
      389 [corrected] rural Amazonians aged 5-90 years in Acre, Brazil. Anemia and iron
      deficiency were diagnosed in 16% and 19% of the population, respectively. Anemia
      was likely to have multiple causes; although nearly half of anemic school
      children and women had altered iron status indicators, only 19.7% of overall
      anemia was attributable to iron deficiency. Geo-helminth infection and a recent
      malaria episode were additional factors affecting iron status indicators in this
      population.

PMID- 17194862
TI  - Experiences of intimate partner violence and related injuries among women in
      Yokohama, Japan.
AB  - We estimated rates of intimate partner violence and related injuries in a sample
      of 1371 women aged 18 to 49 years in Yokohama, Japan. By the age of 30 years,
      14.3% of women who had ever had a partner had experienced violence from that
      partner, and 3.3% had suffered injuries related to such violence. By the time
      women had reached the age of 49 years, these percentages were 19% and 4%,
      respectively. In addition to the need for increased prevention efforts, our
      findings indicate the need for an expanded legal definition of intimate partner
      violence in Japan given that the current definition excludes premarital violence.

PMID- 17194863
TI  - Brief intervention for alcohol use by pregnant women.
AB  - OBJECTIVES: We examined the efficacy of brief intervention as a technique to help
      pregnant women achieve abstinence from alcohol. A second aim was to assess
      newborn outcomes as a function of brief intervention. METHODS: Two hundred fifty
      five pregnant women who were participants in the Public Health Foundation
      Enterprises Management Solutions Special Supplemental Nutrition Program for
      Women, Infants, and Children and who reported drinking alcohol were assigned to
      an assessment-only or a brief intervention condition and followed to their third
      trimester of pregnancy. Brief intervention consisted of 10- to 15-minute sessions
      of counseling by a nutritionist, who used a scripted manual to guide the
      intervention. Newborn outcomes of gestation, birth-weight, birth length, and
      viability were assessed. RESULTS: Women in the brief intervention condition were
      5 times more likely to report abstinence after intervention compared with women
      in the assessment-only condition. Newborns whose mothers received brief
      intervention had higher birthweights and birth lengths, and fetal mortality rates
      were 3 times lower (0.9%) compared with newborns in the assessment-only (2.9%)
      condition. CONCLUSIONS: The success of brief intervention conducted in a
      community setting by nonmedical professionals has significant implications for
      national public health policies.

PMID- 17194865
TI  - Effects of maternal and provider characteristics on up-to-date immunization
      status of children aged 19 to 35 months.
AB  - OBJECTIVES: We examined the effects of maternal and provider characteristics on
      the up-to-date immunization status of children. METHODS: We used data from the
      2003 National Immunization Survey to determine variations in children's up-to
      date status in the 4:3:1:3 immunization series. RESULTS: Low maternal educational
      levels and low socioeconomic status were associated with high 4:3:1:3 series
      completion rates. Also, completion rates were high in Hispanic and non-Hispanic
      Black families with low income-to-poverty ratios. CONCLUSIONS: We found that
      children of less educated mothers and children in Hispanic and non-Hispanic Black
      families with low income-to-poverty ratios were more likely to have completed the
      4:3:1:3 series. Although the reasons for these results need further exploration
      in other data sets, possible factors are Hispanics' positive cultural attitudes
      regarding the needs and importance of young children and provision of information
      on immunizations to low-income minority mothers who access government-subsidized
      health care programs.

PMID- 17194864
TI  - Using participant event monitoring in a cohort study of unintentional injuries
      among children and adolescents.
AB  - OBJECTIVES: We conducted a 3-year cohort study of 407 youths aged 9 to 18 years
      to develop multivariable risk prediction models of agriculture-related injuries.
      METHODS: Data were obtained via participant event monitoring, with youths self
      reporting injuries and exposures in daily diaries over a 13-week period. We
      evaluated data quality by comparing injury self-reports with other injury data.
      RESULTS: Semilogarithmic plots of rates of all unintentional injuries combined
      (US data from 2000) as well as of agriculture-related injuries (US and Canadian
      data from 19 previous studies) graphed as a function of injury severity exhibited
      linearity, as did plots based on the present results. Severity-specific
      unintentional injury rates were 1.4- to 4.3-times higher than national rates,
      suggesting that our methodology can significantly reduce injury underreporting.
      In addition, at each severity level, estimated agriculture-related injury rates
      were 5.8- to 9.3-times higher than rates from previous national, regional, and
      state-based studies. CONCLUSIONS: Our approach to participant event monitoring
      can be implemented with youths aged 9 to 18 years and will yield reliable daily
      data on unintentional injuries.

PMID- 17194866
TI  - Prevalence estimates of overweight and obesity in Cree preschool children in
      northern Quebec according to international and US reference criteria.
AB  - OBJECTIVES: We estimated the prevalence of overweight and obesity in Cree
      Canadian children aged 5 years (n=1044) using international and US growth
      references and examined the longitudinal tracking of weight categories between
      ages 2 and 5 years (n=562). METHODS: Weight categories based on body mass index
      (calculated from measured heights and weights) were derived from the
      International Obesity Task Force (IOTF) and the Centers for Disease Control and
      Prevention (CDC) references. RESULTS: According to the IOTF reference, 52.9% of
      children were overweight (31.6%) or obese (21.3%) whereas with the CDC reference,
      64.9% were overweight (27.5%) or obese (37.4%). The IOTF and CDC references
      provided dissimilar tracking of weight categories. Based on the IOTF reference,
      4.9% of the children who were normal weight at age 2 years were obese at age 5
      years. Based on the CDC reference, 14.9% of children categorized as normal weight
      at age 2 years were obese at age 5 years. CONCLUSIONS: The IOTF reference
      provided more conservative estimates of obesity than the CDC reference, and
      longitudinal analyses showed dissimilar tracking of weight categories with the 2
      references. Public health responses to obesity prevalence estimates should be
      made with awareness of methodological limitations.

PMID- 17194867
TI  - The Black-White disparity in pregnancy-related mortality from 5 conditions:
      differences in prevalence and case-fatality rates.
AB  - OBJECTIVES: We sought to determine whether differences in the prevalences of 5
      specific pregnancy complications or differences in case fatality rates for those
      complications explained the disproportionate risk of pregnancy-related mortality
      for Black women compared with White women in the United States. METHODS: We used
      national data sets to calculate prevalence and case-fatality rates among Black
      and White women for preeclampsia, eclampsia, abruptio placentae, placenta previa,
      and postpartum hemorrhage for the years 1988 to 1999. RESULTS: Black women did
      not have significantly greater prevalence rates than White women. However, Black
      women with these conditions were 2 to 3 times more likely to die from them than
      were White women. CONCLUSIONS: Higher pregnancy-related mortality among Black
      women from preeclampsia, eclampsia, abruptio placentae, placenta previa, and
      postpartum hemorrhage is largely attributable to higher case-fatality rates.
      Reductions in case-fatality rates may be made by defining more precisely the
      mechanisms that affect complication severity and risk of death, including complex
      interactions of biology and health services, and then applying this knowledge in
      designing interventions that improve pregnancy-related outcomes.

PMID- 17194868
TI  - Malnutrition among children younger than 5 years-old in conflict zones of
      Chiapas, Mexico.
AB  - We performed a cross-sectional, community-based survey, supplemented by
      interviews with community leaders in Chiapas, Mexico, to examine the prevalence
      and predictors of child malnutrition in regions affected by the Zapatista
      conflict. The prevalence rates of stunting, wasting, and underweight were 54.1%,
      2.9%, and 20.3%, respectively, in 2666 children aged younger than 5 years.
      Stunting was associated with indigenous ethnicity, poverty, region of residence,
      and intracommunity division. The results indicate that malnutrition is a serious
      public health problem in the studied regions.

PMID- 17194869
TI  - Exposure to lead and length of time needed to make homes lead-safe for young
      children.
AB  - OBJECTIVES: We determined the length of time needed to make homes lead-safe in a
      population of children aged 0 to 6 years with blood lead levels (BLLs) of 20
      micrograms per deciliter (mug/dL) or greater. Reducing this time would reduce
      children's exposure to lead. METHODS: Data came from the Wisconsin Childhood Lead
      Poisoning Prevention Program's comprehensive blood lead surveillance system.
      Analysis was restricted to children whose first BLL test value during 1996-1999
      was between 20 and 40 mug/dL and for whom housing intervention data were
      available (n=382). RESULTS: The median length of time required to make a home
      lead-safe was 465 days. Only 18% of children lived in homes that were made lead
      safe within 6 months; 45% lived in homes requiring more than 18 months to be lead
      safe. CONCLUSIONS: Efforts are needed to reduce the time it takes to make a home
      lead-safe. Although abatement orders always include time limits, improved
      compliance with the orders must be enforced. Greater emphasis should be placed on
      securing lead-safe or lead-free housing for families, thus reducing lead
      exposure.

PMID- 17194870
TI  - The health impact of child labor in developing countries: evidence from cross
      country data.
AB  - OBJECTIVES: Research on child labor and its effect on health has been limited. We
      sought to determine the impact of child labor on children's health by correlating
      existing health indicators with the prevalence of child labor in selected
      developing countries. METHODS: We analyzed the relationship between child labor
      (defined as the percentage of children aged 10 to 14 years who were workers) and
      selected health indicators in 83 countries using multiple regression to determine
      the nature and strength of the relation. The regression included control
      variables such as the percentage of the population below the poverty line and the
      adult mortality rate. RESULTS: Child labor was significantly and positively
      related to adolescent mortality, to a population's nutrition level, and to the
      presence of infectious disease. CONCLUSIONS: Longitudinal studies are required to
      understand the short- and long-term health effects of child labor on the
      individual child.

PMID- 17194872
TI  - The effect of poverty and caregiver education on perceived need and access to
      health services among children with special health care needs.
AB  - OBJECTIVES: We examined the association between several variables and the use of
      specialist physician services, developmental therapies, and prescription
      medications among children with special health care needs (N=38866). METHODS: We
      used a bivariate probit model to estimate whether a given child needed
      specialized services and whether that child accessed those services; we
      controlled for activity limitations and severity of special needs. Variables
      included family income, mother's (or other caregiver's) educational level, health
      insurance coverage, and perceived need for specialized services. We used data
      from the 2001 National Survey of Children with Special Health Care Needs.
      RESULTS: Lower-income and less-educated parents were less likely than higher
      income and more-educated parents to say their special needs children needed
      specialized health services. The probability of accessing specialized health
      services-when needed-increased with both higher family income and insurance
      coverage. CONCLUSIONS: Children with special health care needs have less access
      to health services because their parents do not recognize the need for those
      services. An intervention in the form of information at the family level may be
      an appropriate policy response.

PMID- 17194871
TI  - Framing the public health of caregiving.
AB  - Caregiving has only recently been acknowledged by the nation as an important
      topic for millions of Americans. A psychological or sociological approach to care
      giving services has been most often applied, with little attention to the
      population-based public health outcomes of caregivers. We conceptualize
      caregiving as an emerging public health issue involving complex and fluctuating
      roles. We contend that caregiving must be considered in the context of life span
      needs that vary according to the ages, developmental levels, mental health needs,
      and physical health demands of both caregivers and care recipients.

PMID- 17194873
TI  - Early otitis media among Minnesota American Indians: the Little Ears Study.
AB  - OBJECTIVES: We examined relationships between otitis media risk factors,
      sociodemographic characteristics, and maternal knowledge and attitudes and early
      onset of otitis media. METHODS: Pregnant women from Minnesota American Indian
      reservations and an urban clinic were enrolled in our study between 1998 and
      2001. Follow-up was performed on enrollees' infants until the children were 2
      years old. Research nurses collected data by ear examination, from interviews and
      questionnaires given to enrolled mothers, and otitis media episodes that were
      abstracted from medical records. RESULTS: Sixty-three percent of infants had
      experienced an otitis media episode by 6 months of age. Logistic regression
      analyses showed that maternal otitis media history, infant history of upper
      respiratory infection, and compliance with study visits were significantly
      related to early otitis media onset. Although high percentages of infants were
      exposed to cigarette smoke and other children and were formula fed, these factors
      were not related to otitis media. Mothers' prenatal awareness of otitis media
      risks associated with environmental tobacco smoke exposure and formula feeding
      did not predict their postpartum behaviors. CONCLUSIONS: We found that infant
      history of upper respiratory infection and maternal otitis media history are risk
      factors for early otitis media in American Indian infants. Mothers' prepartum
      knowledge and attitudes regarding otitis media did not predict their postpartum
      avoidance of risk behaviors.

PMID- 17194874
TI  - Assistive technology use among adolescents and young adults with spina bifida.
AB  - OBJECTIVES: We sought to determine the use of assistive technology among a
      population of individuals with spina bifida. METHODS: We performed a descriptive
      analysis of individuals aged 13 to 27 years diagnosed with myelomeningocele
      (n=348) using data obtained from an existing database at Children's Hospital and
      Regional Medical Center, Seattle, Washington. We summarized disease
      characteristics, utilization of assistive technology, community and self-care
      independence, and other variables. RESULTS: Eighty-four percent of the
      respondents lived with at least 1 of their natural parents. Fifty-seven percent
      used wheelchairs, 35% used braces, and 23% used walking aids. Independent self
      care was a common skill, but 72% reported limited participation in structured
      activities. Half were aged 18 years or older; of those, only 50% had completed
      high school and 71% were unemployed. Those aged younger than 18 years were all
      still in school (100%). CONCLUSIONS: Adolescents and young adults with spina
      bifida rely on assistive technology and specialized care routines to maintain
      their health. Assistive technology use for mobility is common; little is known
      about secondary complications associated with use of these technologies or the
      use of assistive technology to address learning disabilities and other societal
      barriers. Underutilization of assistive technology could delay successful
      transitions to independent living and community participation.

PMID- 17194875
TI  - Heart disease and stroke statistics--2007 update: a report from the American
      Heart Association Statistics Committee and Stroke Statistics Subcommittee.

PMID- 17194876
TI  - Reduced poststroke mortality in patients with stroke and atrial fibrillation
      treated with anticoagulants: results from a Danish quality-control registry of
      22,179 patients with ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The preventive effect of anticoagulation in patients with
      stroke and atrial fibrillation (AF) is documented only in trials of minor stroke.
      Although anticoagulation reduced stroke recurrence, those trials did not
      demonstrate an influence of anticoagulation on survival. METHODS: A nationwide
      registry that was started in 2001 with the aim of registering all hospitalized
      stroke patients in Denmark now includes 24 791 patients. We studied the survival
      of patients with ischemic stroke and AF with respect to anticoagulation
      treatment. All underwent an evaluation for stroke severity (according to the
      Scandinavian Stroke Scale), computed tomography scan, and an evaluation for
      cardiovascular risk factors. Follow-up duration was 4 years (mean, 1.2 years).
      RESULTS: Of all patients, 22 179 (89.4%) experienced an ischemic stroke. In
      total, 3670 (16.5%) had AF, and 1909 had no contraindication to anticoagulation
      treatment. Anticoagulation treatment was initiated in 1149 of these patients
      (60.2%) but omitted in 760 (39.8%) despite no contraindication to such treatment.
      Of the patients so treated, 18.9% died during follow-up versus 45.2% without
      treatment. Patients who received treatment were younger (76.7+/-9.5 versus 80.7+/
      9.0 years, P<0.0001) and had less severe strokes (Scandinavian Stroke Scale
      score, 42.0+/-15.0 versus 33.6+/-18.2, P<0.0001). A Cox proportional-hazards
      model was built to study the effect of anticoagulation on survival in patients
      without contraindications to treatment while controlling for stroke severity,
      sex, and cardiovascular risk factors. Patients without anticoagulation treatment
      were at greater risk of dying (hazard ratio=1.91, 95% CI=1.44 to 2.52) compared
      with patients who received anticoagulation treatment. CONCLUSIONS: Our data
      suggest that anticoagulation treatment reduces poststroke mortality in patients
      with ischemic stroke and AF.

PMID- 17194877
TI  - Is it time for a cardiovascular primary prevention trial in the elderly?
AB  - BACKGROUND AND PURPOSE: Statins have been shown conclusively to reduce the risk
      of cardiovascular events in subjects with clinical cardiovascular disease or
      diabetes aged 65 to 80 years of age. However, few data are available for primary
      prevention of cardiovascular disease in those aged > or =70 years. SUMMARY OF
      REVIEW: A moderate-dose statin was of little benefit in a population aged 70 to
      82 years when given for 3 years in the setting of suboptimally treated blood
      pressure. More evidence supports the use of blood pressure-lowering medications,
      but few data are available regarding the appropriate blood pressure target and
      most effective agents in the elderly. Some evidence also suggests that the
      elderly could experience higher mortality with antihypertensive treatment. These
      findings, along with greater safety concerns and an increasing number of
      competing risks and medical conditions with advancing age, make it imperative to
      carefully evaluate the risk/benefit balance from treating hypercholesterolemia
      and hypertension in persons aged > or =70 years. CONCLUSIONS: We propose a 5-year
      2x2 factorial trial of primary prevention in the elderly that will (1) evaluate
      whether statin therapy will reduce the risk of cardiovascular events when added
      to the treatment of hypertension to achieve a blood pressure <140/90 mm Hg in
      most patients and (2) determine the most appropriate blood pressure regimen for
      the prevention of cardiovascular and renal events.

PMID- 17194878
TI  - Neurological symptoms in type A aortic dissections.
AB  - BACKGROUND AND PURPOSE: Aortic dissection typically presents with severe chest or
      back pain. Neurological symptoms may occur because of occlusion of supplying
      vessels or general hypotension. Especially in pain-free dissections diagnosis can
      be difficult and delayed. The purpose of this study is to analyze the association
      between type A aortic dissection and neurological symptoms. METHODS: Clinical
      records of 102 consecutive patients with aortic dissection (63% male, median age
      58 years) over 7.5 years were analyzed for medical history, preoperative clinical
      characteristics, treatment and outcome with main emphasis on neurological
      symptoms. RESULTS: Thirty patients showed initial neurological symptoms (29%).
      Only two-thirds of them reported chest pain, and most patients without initial
      neurological symptoms experienced pain (94%). Neurological symptoms were
      attributable to ischemic stroke (16%), spinal cord ischemia (1%), ischemic
      neuropathy (11%), and hypoxic encephalopathy (2%). Other frequent symptoms were
      syncopes (6%) and seizures (3%). In half of the patients, neurological symptoms
      were transient. Postoperatively, neurological symptoms were found in 48% of all
      patients encompassing ischemic stroke (14%), spinal cord ischemia (4%), ischemic
      neuropathy (3%), hypoxic encephalopathy (8%), nerve compression (7%), and
      postoperative delirium (15%). Overall mortality was 23% and did not significantly
      differ between patients with and without initial neurological symptoms or
      complications. CONCLUSIONS: Aortic dissections might be missed in patients with
      neurological symptoms but without pain. Neurological findings in elderly
      hypertensive patients with asymmetrical pulses or cardiac murmur suggest
      dissection. Especially in patients considered for thrombolytic therapy in acute
      stroke further diagnostics is essential. Neurological symptoms are not
      necessarily associated with increased mortality.

PMID- 17194879
TI  - Uncertainty of management of blood pressure and lipids in the elderly: time for a
      primary prevention trial.

PMID- 17194880
TI  - Is diabetic retinopathy an independent risk factor for ischemic stroke?
AB  - BACKGROUND AND PURPOSE: The relationship between diabetic retinopathy and
      ischemic stroke is uncertain and examined in this study. METHODS: A population
      based, prospective cohort study of 1617 middle-aged persons with diabetes.
      Diabetic retinopathy signs were ascertained from retinal photographs, and
      incident ischemic stroke events were prospectively identified and validated.
      RESULTS: Over an average follow-up of 7.8 years, there were 75 ischemic stroke
      events. After adjustment for age, gender, race, center, 6-year mean arterial
      blood pressure, anti-hypertensive treatment use, fasting glucose, insulin
      treatment, duration of diabetes, high-density lipoprotein and low-density
      lipoprotein cholesterol levels and cigarette smoking status, diabetic retinopathy
      was associated with an increased risk of ischemic stroke (hazard rate ratio,
      2.34; 95% CI, 1.13 to 4.86). CONCLUSIONS: Diabetic retinopathy predicts incident
      ischemic stroke in people with diabetes, independent of other risk factors.

PMID- 17194882
TI  - Spontaneous and endothelial-independent vasodilation are impaired in patients
      with spontaneous carotid dissection: a case-control study.
AB  - BACKGROUND AND PURPOSE: We undertook this case-control study in patients with
      unilateral spontaneous dissection of the cervical internal carotid artery to
      investigate spontaneous and endothelium-independent dilation of the nondissected,
      contralateral carotid arteries and the ipsilateral brachial artery using high
      resolution ultrasound. METHODS: Spontaneous and endothelial-independent
      (nitroglycerin-mediated) absolute and relative dilation were assessed in the
      internal and common carotid and brachial arteries of 27 patients with unilateral
      spontaneous dissection of the cervical internal carotid artery and 27 age- and
      sex-matched healthy controls. RESULTS: Absolute and relative spontaneous and
      endothelial-independent dilation of the carotid, but not brachial arteries, were
      significantly lower in patients as compared with controls. CONCLUSIONS:
      Vasodilation abnormalities may be a predisposing factor for spontaneous
      dissection of the cervical internal carotid artery.

PMID- 17194883
TI  - Quantitative perihematomal blood flow in spontaneous intracerebral hemorrhage
      predicts in-hospital functional outcome.
AB  - BACKGROUND AND PURPOSE: Few data on xenon computed tomography-based quantitative
      cerebral blood flow (CBF) in spontaneous intracerebral hemorrhage have been
      reported. We correlated perihematomal CBF in a retrospective series of 42
      subacute spontaneous intracerebral hemorrhage patients undergoing xenon computed
      tomography with in-hospital discharge status and mortality. METHODS: We
      calculated 3 area-weighted mean CBF values: (1) within the computed tomography
      visible rim of perihematomal edema, (2) within a 1-cm marginal radius around the
      hematoma, and (3) all cortical regions of interest immediately adjacent to the
      hematoma. Primary outcomes were in-hospital mortality and discharge status
      (ordinally as 0=home, 1=acute rehabilitation, 2=nursing home, 3=death). Discharge
      status was used as a surrogate for in-hospital functional outcome. RESULTS:
      Median hematoma volume was 14.4 cm(3) (range, 2 to 70). Median perihematomal (low
      attenuation rim) CBF was 21.9 cm(3).100 g(-1).min(-1) (range, 6.1 to 81.1), and
      the median 1-cm marginal radius CBF was 26.8 cm(3).100 g(-1).min(-1) (range, 10.8
      to 72.8). The median regional cortical CBF was 26.7 cm(3).100 g(-1).min(-1)
      (range, 6.9 to 72.6). Eight patients had 1-cm marginal radius or regional
      cortical CBF values <20 cm(3).100 g(-1).min(-1). Hematoma volume (odds ratio
      [OR], 1.68 per 10-cm(3) volume; P=0.036) and intraventricular hemorrhage (OR,
      1.88 per grade of intraventricular hemorrhage; P=0.036) predicted mortality. Two
      CBF measures, hydrocephalus, and IVH predicted poor in-hospital functional
      outcome in bivariate analysis. Each CBF measure (OR, 0.34 to 0.43; P<0.001 to
      0.003) and intraventricular hemorrhage (OR, 3.42; P<0.001) predicted in-hospital
      functional outcome in multivariable analyses. CONCLUSIONS: Most spontaneous
      intracerebral hemorrhage patients lack perihematomal penumbra. Perihematomal CBF
      independently predicts in-hospital discharge status but not in-hospital
      mortality. Further studies are warranted to determine whether perihematomal CBF
      predicts long-term functional outcomes.

PMID- 17194881
TI  - Hemorrhage rate in patients with Spetzler-Martin grades IV and V arteriovenous
      malformations: is treatment justified?
AB  - BACKGROUND AND PURPOSE: We sought to examine the prospective annual risk of
      hemorrhage in patients harboring Spetzler-Martin grades IV and V arteriovenous
      malformations (AVMs) before and after initiation of treatment. METHODS: Medical
      records of 61 consecutive patients presenting with Spetzler-Martin grades IV and
      V AVMs were retrospectively reviewed for demographics, angiographic features,
      presenting symptom(s), and time of all hemorrhage events, before or after
      treatment initiation. Pretreatment hemorrhage rates (excluding hemorrhages at
      presentation) and posttreatment rates were subsequently calculated. Modified
      Rankin Scale (mRS) scores before and after treatment were recorded. RESULTS: The
      annual pretreatment hemorrhage rate for all patients was 10.4% per year (95% CI,
      2.2 to 15.4%), 13.9% (95% CI, 3.5 to 22.1%) in patients with hemorrhagic
      presentation and 7.3% (2.6 to 14.3%) in patients with nonhemorrhagic
      presentation. Posttreatment hemorrhage rates were 6.1% per year (95% CI, 2.5 to
      13.2%) for all patients, 5.6% (95% CI, 2.1 to 11.8%) for patients presenting with
      hemorrhage and 6.4% (95% CI, 1.6 to 10.1%) in patients with nonhemorrhagic
      presentation. A noninferiority test showed that the posttreatment hemorrhage rate
      was less than or equal to the pretreatment hemorrhage rate (P<0.0001), with some
      indication that the reduction was greatest in patients with hemorrhagic
      presentation. Of the 62 patients, 51 (82%) had an mRS score of 0 to 2 before
      treatment, and 47 (76%) had an mRS score of 0 to 2 at the last follow-up after
      treatment. CONCLUSIONS: The annual rate of hemorrhage in grades IV and V AVMs is
      higher in this series than reported for all AVMs, which may reflect some referral
      bias in this single-center study. Nevertheless, initiation of treatment does not
      appear to increase the rate of subsequent hemorrhage. Treatment for these lesions
      may be warranted, given their poor natural history.

PMID- 17194884
TI  - Insular cortex hypoperfusion and acute phase blood glucose after stroke: a CT
      perfusion study.
AB  - BACKGROUND AND PURPOSE: Insular cortex ischemia is proposed to mediate a
      sympathetic stimulus that leads to acute hyperglycemia after stroke. METHODS: We
      retrospectively analyzed insular perfusion on perfusion CT (median 180 minutes
      after onset) in 35 patients. RESULTS: We found no association of hypoperfusion
      (relative cerebral blood flow <0.51) with early (<6 hours) or delayed (<72 hours)
      hyperglycemia, or hemispheric lateralization. CONCLUSIONS: Insular cortex
      hypoperfusion <6 hours after stroke onset was not associated with hyperglycemia.

PMID- 17194885
TI  - Mode of onset predicts etiological diagnosis of arterial ischemic stroke in
      children.
AB  - BACKGROUND AND PURPOSE: In children, early differentiation among various
      etiologies of arterial ischemic stroke (AIS) is important. Cerebral arteriopathy
      is a frequently identified cause of childhood stroke. Children with
      arteriopathies require a different therapeutic approach from children with AIS of
      nonarteriopathic origin. We aimed to investigate the association between temporal
      features of the onset of neurological symptoms and stroke etiology in children
      with AIS. METHODS: From a consecutive cohort of children (6 months to 18 years)
      with a confirmed diagnosis of AIS at one center, we selected all patients with
      transient cerebral arteriopathy (n=10), postvaricella angiopathy (n=20),
      dissection (n=8), cardio-embolic (n=8), and cryptogenic stroke (n=10). We
      retrospectively reviewed medical charts for mode of onset and classified the
      onset as either abrupt, reaching maximum severity of symptoms within 30 minutes,
      or nonabrupt, including a progressing, stuttering, or recurring course. We
      compared the mode of onset in patients with known cerebral arteriopathy to those
      with nonarteriopathic stroke using multivariate logistic regression modeling.
      RESULTS: There were no significant differences for age, gender, location of
      infarction, seizures, and headache between the arteriopathic and nonarteriopathic
      group. Most children with nonarteriopathic AIS had an abrupt onset (72%),
      compared with 32% in children with arteriopathic stroke. With nonabrupt onset,
      the odds of having an arteriopathic etiology was 6.1 (95% CI, 1.6 to 22.8;
      P=0.007) after correction for possible confounders. CONCLUSIONS: Mode of onset
      predicts etiological diagnosis of childhood AIS and may guide prioritization of
      ancillary investigations and choice of treatment. A nonabrupt onset of symptoms
      is associated with arteriopathic stroke, particularly with presumed inflammatory
      arteriopathies.

PMID- 17194887
TI  - Efficient tracking of non-iron-labeled mesenchymal stem cells with serial MRI in
      chronic stroke rats.
AB  - BACKGROUND AND PURPOSE: Although stem cell-based treatments for neurodegenerative
      diseases have advanced rapidly, there is currently no clinically available method
      to monitor the fate of transplanted cells in the brain. METHODS: To use magnetic
      resonance imaging for tracking transplanted stem cells in the ischemic rat brain,
      we used the cellular labeling substance Effectene to transfect a standard
      contrast agent (Gd-DTPA) into immortalized human bone marrow stromal cells.
      RESULTS: The transfection efficiency of this method was up to 90%, which is
      substantially better than pure spontaneous endocytosis or other transfection
      agents. In addition, cellular uptake of Gd-DTPA in vitro was maintained for >28
      days. Therefore, we could follow transplanted stem cell migration and homing into
      the penumbric area. Using double immunofluorescence, the transplanted cells were
      seen to differentiate into glial cells, neurons and vascular endothelial cells.
      Cortical neurochemical activity as evaluated by proton magnetic resonance
      spectroscopy ((1)H-MRS) also increased considerably after immortalized human bone
      marrow stromal cell transplantation. CONCLUSIONS: This method of tracking
      immortalized human bone marrow stromal cells is highly efficient and allows for
      nontoxic labeling of cells.

PMID- 17194886
TI  - Effects of triflusal and aspirin in a rat model of cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Neuroinflammation plays a critical role in the
      pathogenesis of cerebral ischemia. Triflusal, a selective cyclooxygenase-2, and
      its active metabolite 3-hydroxy-4-trifluoromethylbenzoic acid may inhibit
      apoptosis and inflammation after cerebral ischemia. An in vivo model of cerebral
      ischemia was used to investigate the effects of triflusal and aspirin treatment
      on infarct volume, and inflammation after cerebral ischemia in the rat. METHODS:
      Male Wistar rats were subjected to a permanent right-sided middle cerebral artery
      occlusion. Rats received oral administration of either triflusal or aspirin.
      After 3 days after surgery, immunostaining was used to detect neuroinflammatory
      cells and molecules, and infarct volumes were measured. RESULTS: Both triflusal
      and aspirin at a dose of 30 mg/kg but not 10 mg/kg significantly reduced infarct
      volume compared with vehicle treatment. Middle cerebral artery occlusion resulted
      in increased astrocyte and heat shock protein-27 (Hsp27) immunostaining in the
      ipsilateral cortex. Triflusal (30 mg/kg) or aspirin treatment (30 mg/kg) did not
      reduce the levels of GFAP or Hsp27 immunostaining. Triflusal (30 mg/kg) also
      significantly decreased the protein levels of IL-Ibeta but not nuclear factor
      kappa B or tumor necrosis factor-alpha in the cortex ipsilateral to the middle
      cerebral artery occlusion. CONCLUSIONS: The results suggest that triflusal and
      aspirin appear to be equally neuroprotective against middle cerebral artery
      occlusion-induced cerebral ischemia. Therefore, strong rationale exists to
      continue the neuroprotective examination of triflusal in brain injury.

PMID- 17194888
TI  - Multiple system utilization and mortality for veterans with stroke.
AB  - BACKGROUND AND PURPOSE: Many Veteran Health Administration (VHA) enrollees
      receive health services outside the VHA system. However, limited information is
      available about poststroke utilization and mortality by veterans who used
      multiple sources of health care. This study assessed the likelihood of 12-month
      poststroke rehospitalization and mortality of veterans who used VHA only versus
      those who used multiple sources of care. METHODS: Our retrospective observational
      study examined veterans living in Florida and diagnosed with acute stroke. We
      categorized users into 4 groups: VHA-only, VHA-Medicare, VHA-Medicaid, and VHA
      Medicare-Medicaid based on their use of each health care program. Logistic
      regression models were fitted for 12-month poststroke general rehospitalization,
      recurrent stroke readmission, and mortality, adjusting for sociodemographic and
      clinical factors. RESULTS: The sample consisted of 29% VHA-only users, 61% VHA
      Medicare users, 3% VHA-Medicaid users, and 7% VHA-Medicare-Medicaid triple users.
      Compared with the VHA-only users, multiple system users were significantly more
      likely to be rehospitalized for any cause and for recurrent stroke 12-months
      postindex. Mortality outcomes depended on when the outcome was measured; at the
      index admission date, we found no significant difference in mortality across the
      user groups; at the index discharge date, the VHA-only users was less likely to
      die within the first 12 months than the users of the 2 dual groups (VHA-Medicare
      and VHA-Medicaid). CONCLUSIONS: Multiple health care source use was common among
      VHA enrollees with acute stroke in Florida. Multiple system users were more
      likely to be rehospitalized and the mortality outcomes were dependent on when the
      outcome was measured.

PMID- 17194889
TI  - Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and
      fenofibrate, on adiponectin level.
AB  - OBJECTIVE: Adiponectin is adipose-specific secretory protein and acts as anti
      diabetic and anti-atherosclerotic molecule. We previously found peroxisome
      proliferators response element in adiponectin promoter region, suggesting that
      peroxisome proliferator-activated receptor (PPAR) ligands elevate adiponectin.
      Fibrates are known to be PPARalpha ligands and were shown to reduce risks of
      diabetes and cardiovascular disease. Effect of fibrates on adiponectin has not
      been clarified, whereas thiazolidinediones enhance adiponectin. Thus, we explored
      the possibility and mechanism that fibrates enhance adiponectin in humans, mice,
      and cells. METHODS AND RESULTS: Significant increase of serum adiponectin was
      observed in bezafibrate-treated subjects compared with placebo group in patients
      enrolled in The Bezafibrate Infarction Prevention study. Higher baseline
      adiponectin levels were strongly associated with reduced risk of new diabetes.
      Fibrates, bezafibrate and fenofibrate, significantly elevated adiponectin levels
      in wild-type mice and 3T3-L1 adipocytes. Such an effect was not observed in
      PPARalpha-deficient mice and adipocytes. Fibrates activated adiponectin promoter
      but failed to enhance its activity when the point mutation occurred in peroxisome
      proliferators response element site and the endogenous PPARalpha was knocked down
      by PPARalpha-RNAi. CONCLUSIONS: Our results suggest that fibrates enhance
      adiponectin partly through adipose PPARalpha and measurement of adiponectin might
      be a useful tool for searching subjects at high risk for diabetes.

PMID- 17194890
TI  - Increasing peripheral artery intima thickness from childhood to seniority.
AB  - BACKGROUND: Using new, very high-resolution ultrasound biomicroscopy, we examined
      the thickness of artificial layers of silicone and intima thickness (IT) of
      radial and anterior tibial arteries in healthy subjects and in patients with
      vascular disease. METHODS AND RESULTS: Silicone layers of varying thicknesses and
      mesenteric artery specimens obtained from 18 patients undergoing colectomy were
      measured by both ultrasound biomicroscopy (55 MHz) and morphometry. There was
      high correlation (r>0.9; P<0.0001) between IT and intima area versus ultrasound
      biomicroscopy. In 90 healthy subjects (aged between 10 and 90 years), radial and
      anterior tibial arterial IT and intima-media thickness were measured, as was
      carotid intima-media thickness in 56 of these subjects. Age was strongly related
      with both media thickness and IT of both peripheral arteries. Correlations were
      found between carotid intima-media thickness and both radial and anterior tibial
      IT/intima-media thickness (r=0.44 to 0.53; P<0.0001). The IT-to-lumen diameter
      ratio increased with age and was larger at all ages in the anterior tibial artery
      (0.067+/-0.034) versus the radial artery (0.036+/-0.012; P<0.0001). A thicker
      radial intimal layer was found in patients with peripheral artery disease.
      CONCLUSION: This study is the first to our knowledge in humans to show the
      feasibility of measuring IT of the radial and anterior tibial arteries using very
      high-resolution ultrasound. IT progresses with age, and the IT-to-lumen diameter
      ratio is largest in the arteries of the foot. Assessment of IT by ultrasound
      biomicroscopy may aid in detecting early peripheral vascular abnormalities.

PMID- 17194891
TI  - Phagocytic NADPH oxidase-dependent superoxide production stimulates matrix
      metalloproteinase-9: implications for human atherosclerosis.
AB  - OBJECTIVE: Data suggest that matrix metalloproteinase-9 (MMP-9) has a role in
      atherosclerosis. The phagocytic NADPH oxidase has been also associated with
      atherosclerosis. This study aimed to investigate the association between
      phagocytic NADPH oxidase and MMP-9 in human atherosclerosis. METHODS AND RESULTS:
      In vitro experiments performed in human monocytes showed that NADPH oxidase
      activation enhanced MMP-9 secretion and activity, determined by enzyme-linked
      immunosorbent assay and zymography, respectively. Immunohistochemical study
      showed that phagocytic NADPH oxidase localized with MMP-9 in endarterectomies
      from patients with carotid stenosis. In addition, a positive relationship
      (P<0.001) was found between phagocytic NADPH oxidase-dependent superoxide
      production determined with lucigenin and plasma MMP-9 levels in 188 asymptomatic
      subjects free of overt clinical atherosclerosis. In multivariate analysis, this
      association remained significant after adjustment for cardiovascular risk
      factors. Interestingly, subjects in the upper quartile of superoxide production
      exhibited the highest values of MMP-9, oxidized low-density lipoprotein,
      nitrotyrosine, carotid intima media thickness, and an increased presence of
      carotid plaques. CONCLUSIONS: Enhanced NADPH oxidase-dependent *O2(-) production
      stimulates MMP-9 in monocytes and this relationship may be relevant in the
      atherosclerotic process. Moreover, MMP-9 emerges as an important mediator of the
      phagocytic NADPH oxidase-dependent oxidative stress in atherosclerosis.

PMID- 17194892
TI  - KLF2 suppresses TGF-beta signaling in endothelium through induction of Smad7 and
      inhibition of AP-1.
AB  - OBJECTIVE: The flow-responsive Kruppel-like factor 2 (KLF2) is crucial for
      maintaining endothelial cell quiescence. Here, we describe its detailed effects
      on transforming growth factor-beta (TGF-beta) signaling, which normally has
      proatherogenic effects on endothelium. METHODS AND RESULTS: In-depth analysis of
      genome-wide expression data shows that prolonged lentiviral-mediated
      overexpression of KLF2 in human umbilical vein endothelial cells (HUVECs)
      diminishes the expression of a large panel of established TGF-beta-inducible
      genes. Both baseline and TGF-beta-induced expression levels of plasminogen
      activator inhibitor 1 (PAI-1) and thrombospondin-1 are greatly diminished by
      KLF2. Using a combination of ectopic expression, small interfering RNA-mediated
      knockdown, and promoter activity assays, we show that KLF2 partly inhibits the
      phosphorylation and subsequent nuclear accumulation of Smad2, thereby suppressing
      the TGF-beta-induced Smad4-mediated transcriptional activity. This is achieved
      through TGF-beta-independent induction of inhibitory Smad7. Additionally, a full
      inhibition of TGF-beta signaling is functionally achieved through a simultaneous
      suppression of activator protein 1 (AP-1), which is an essential cofactor for TGF
      beta-dependent transcription of many genes. CONCLUSIONS: The concerted mechanism
      by which KLF2 inhibits TGF-beta signaling through induction of inhibitory Smad7
      and attenuation of AP-1 activity provides a novel mechanism by which KLF2
      contributes to sustaining a quiescent, atheroprotective status of vascular
      endothelium.

PMID- 17194893
TI  - Chimeric VEGF-ENZ7/PlGF specifically binding to VEGFR-2 accelerates skin wound
      healing via enhancement of neovascularization.
AB  - OBJECTIVE: VEGF-E(NZ7)/PlGF molecules composed of Orf virus-derived VEGF-E(NZ7)
      and human PlGF1 were previously proven to be potent angiogenic factors
      stimulating angiogenesis without significant enhancement of vascular leakage and
      inflammation in vivo. For its future clinical application, there is a pressing
      need to better understand the beneficial effects of VEGF-E(NZ7)/PlGF during wound
      healing in adulthood. METHODS AND RESULTS: In this study, several angiogenic
      factors were administrated to skin punched wounds of both wild-type and diabetic
      mice. The treatment with VEGF-E(NZ7)/PlGF accelerated wound closure accompanied
      with enhanced angiogenesis, the process was occurring slightly faster than that
      in VEGF-A164 group. Moreover, the macrophage infiltration and lymphangiogenesis
      level in healed wounds were strikingly lower in VEGF-E(NZ7)/PlGF group than VEGF
      A164 group, suggesting that the increased inflammation was the key issue
      preventing speedy wound healing of VEGF-A164-treated skin. Considering clinical
      safety, we further examined the antigenicity of chimeric VEGF-E(NZ7)/PlGF.
      Compared with the original VEGF-E(NZ7), the immunogenicity of VEGF-E(NZ7)/PlGF
      molecules was markedly decreased in mice and squirrel monkeys with the increase
      of PlGF1 humanized ratio. CONCLUSION: These results indicate that VEGF
      E(NZ7)/PlGF molecules are superior to VEGF-A for the acceleration of either
      normal or delayed skin wound healing and might be regarded as potential drugs in
      therapeutic angiogenesis.

PMID- 17194894
TI  - In vivo actions of angiopoietins on quiescent and remodeling blood and lymphatic
      vessels in mouse airways and skin.
AB  - OBJECTIVE: We investigated and compared the in vivo effects of all four
      angiopoietins (COMP-Ang1, Ang2, Ang3, and Ang4) on blood and lymphatic vascular
      remodeling in adult mice. We analyzed the microvasculature of trachea and ear
      skin, and compared quiescent skin microvasculature with that during wound
      healing. METHODS AND RESULTS: We were able to achieve similar levels of
      relatively long-term and sustained circulating expression of each angiopoietin
      using an adenoviral delivery system. Two weeks after treatment, we observed
      tracheal blood and lymphatic vascular enlargement, and lymphatic filopodia
      formation, with the following order of potency: COMP-Ang1>Ang3=Ang4>Ang2. Co
      treatment with Ang2 attenuated Ang1-induced tracheal blood and lymphatic
      remodeling. In the normal ear skin, all angiopoietins induced blood vessel
      enlargement, whereas none induced lymphatic vascular remodeling. However, in the
      healing margin of ear skin wounds, all angiopoietins strongly induced lymphatic
      vascular enlargement and formation of lymphatic sprouts and filopodia, while they
      potentiated blood vascular enlargement. Co-treatment of Ang2 with Ang1 produced
      an additive effect on these changes. CONCLUSION: This study, one of the first to
      our knowledge to characterize the in vivo actions of all 4 angiopoietins, may
      expand the current concepts for use of angiopoietins for therapeutic angiogenesis
      and lymphangiogenesis.

PMID- 17194895
TI  - Heparin cofactor II modulates the response to vascular injury.
AB  - Heparin cofactor II (HCII) has several biochemical properties that distinguish it
      from other serpins: (1) it specifically inhibits thrombin; (2) the mechanism of
      inhibition involves binding of an acidic domain in HCII to thrombin exosite I;
      and (3) the rate of inhibition increases dramatically in the presence of dermatan
      sulfate molecules having specific structures. Human studies suggest that high
      plasma HCII levels are protective against in-stent restenosis and
      atherosclerosis. Studies with HCII knockout mice directly support the hypothesis
      that HCII interacts with dermatan sulfate in the arterial wall after endothelial
      injury and thereby exerts an antithrombotic effect. In addition, HCII deficiency
      appears to promote neointima formation and atherogenesis in mice. These results
      suggest that HCII plays a unique and important role in vascular homeostasis.

PMID- 17194896
TI  - Genomics of foam cells and nonfoamy macrophages from rabbits identifies arginase
      I as a differential regulator of nitric oxide production.
AB  - OBJECTIVE: Conversion of macrophages to foam cells is a critical step in the
      initiation and progression of atherosclerosis. We sought to identify genes
      differentially regulated in foam cells, since these are likely to include new
      targets for intervention. METHODS AND RESULTS: We used suppression subtraction
      hybridization to compare foam cells and nonfoamy macrophages isolated from
      subcutaneous granulomas of rabbits fed a cholesterol-rich or normal chow diet and
      confirmed upregulation of 3 genes, including matrix metalloproteinase-12 (mRNA
      2.0-fold, P<0.005; protein 3.9-fold, P<0.03). Arginase-I mRNA showed the biggest
      decrease among 11 downregulated genes in foam cells (2.7-fold, P<0.001) and was
      accompanied by significantly reduced arginase enzymatic activity (60-fold,
      P<0.01). Arginase-I competes for substrate L-arginine with nitric oxide synthase
      and consequently nitric oxide production was significantly increased (3-fold,
      P<0.02) in foam cells compared with nonfoamy macrophages despite no difference in
      nitric oxide synthase isoenzyme expression. We validated upregulation of matrix
      metalloproteinase-12 and downregulation of arginase-1 in foam cells of rabbit and
      human atherosclerotic plaques. CONCLUSIONS: Our study identified several
      differentially expressed genes in foam cells and nonfoamy macrophages derived
      from live rabbits. The altered pattern of gene expression in foam cells is likely
      to influence atherosclerosis formation and stability.

PMID- 17194897
TI  - Regulation of Triglyceride Metabolism. III. Emerging role of lipid droplet
      protein ADFP in health and disease.
AB  - ADFP is the major lipid droplet protein present in all cells that accumulate
      lipids either normally or abnormally. Although discovered about 15 years ago, it
      was only in the last few years that we began to have a working knowledge of its
      possible role in lipid droplet homeostasis at the whole organism level. In this
      perspective, we concentrate on the potential function of ADFP in various tissues.
      Space limitation has precluded a complete cataloging of all publications on the
      topic. We instead highlight some of the salient developments in the last few
      years.

PMID- 17194898
TI  - Long-term feeding of various fat diets modulates azoxymethane-induced colon
      carcinogenesis through Wnt/beta-catenin signaling in rats.
AB  - The Wnt signaling pathway plays an essential role in carcinogenesis, and the
      amount of fat intake and composition of dietary fatty acids are crucial factors
      for colon carcinogenesis. We investigated whether various dietary fats affected
      the Wnt signaling pathway of colon tumorigenesis in azoxymethane (AOM)-treated
      rats. Male Sprague-Dawley rats were given intraperitoneal injections of AOM and
      supplemented with 10% corn, olive, beef, and fish oil for 44 wk. Aberrant crypt
      foci (ACF) and tumors were examined at 12 and 44 wk. Normal appearing colon
      mucosal proliferation and apoptosis were evaluated by 5-bromo-2'-deoxyuridine
      (BrdU) incorporation and percentages of fragmented DNA, respectively. Expressions
      of beta-catenin, cyclin D(1), Wnt2, Wnt3, and Wnt5a of normal appearing colon
      mucosa were analyzed by Western blot analysis. Long-term dietary corn oil and
      beef tallow increased ACF, tumor incidence, and tumor numbers in AOM-treated
      rats. In contrast, both olive and fish oil inhibited them. Dietary corn oil and
      beef tallow increased BrdU incorporation and the expression of cytosolic beta
      catenin and cyclin D(1) and decreased apoptosis in the colon mucosa. Expressions
      of Wnt2 and Wnt3 in rats fed with beef tallow and Wnt5a in rats fed with corn oil
      increased with or without AOM-treatment. BrdU-incorporated cells were often
      observed at the tops of crypts in rats fed with beef tallow, whereas this was not
      observed in rats fed with the other diet. Long-term high intake of corn oil and
      beef tallow enhanced cell proliferation through Wnt signaling and modulated the
      distribution of proliferating cells, which might contribute to promoting effects
      in colon tumorigenesis.

PMID- 17194899
TI  - Crucial role of antioxidant proteins and hydrolytic enzymes in pathogenicity of
      Penicillium expansum: analysis based on proteomics approach.
AB  - Penicillium expansum, a widespread filamentous fungus, is a major causative agent
      of fruit decay and may lead to the production of mycotoxin that causes harmful
      effects on human health. In this study, we compared the cellular and
      extracellular proteomes of P. expansum in the absence and presence of borate,
      which affects the virulence of the fungal pathogen. The differentially expressed
      proteins were identified using ESI-Q-TOF-MS/MS. Several proteins related to
      stress response (glutathione S-transferase, catalase, and heat shock protein 60)
      and basic metabolism (glyceraldehyde-3-phosphate dehydrogenase, dihydroxy-acid
      dehydratase, and arginase) were identified in the cellular proteome. Catalase and
      glutathione S-transferase, the two antioxidant enzymes, exhibited reduced levels
      of expression upon exposure to borate. Because catalase and glutathione S
      transferase are related to oxidative stress response, we further investigated the
      reactive oxygen species (ROS) levels and oxidative protein carbonylation (damaged
      proteins) in P. expansum. Higher amounts of ROS and carbonylated proteins were
      observed after borate treatment, indicating that catalase and glutathione S
      transferase are important in scavenging ROS and protecting cellular proteins from
      oxidative damage. Additionally to find secretory proteins that contribute to the
      virulence, we studied the extracellular proteome of P. expansum under stress
      condition with reduced virulence. The expression of three protein spots were
      repressed in the presence of borate and identified as the same hydrolytic enzyme,
      polygalacturonase.

PMID- 17194900
TI  - Radiation therapy can still be used safely in combined modality approaches in
      patients with Hodgkin's lymphoma.

PMID- 17194901
TI  - Toward the optimal use of androgen suppression therapy in the radiotherapeutic
      management of prostate cancer.

PMID- 17194902
TI  - Comparison of intensive chemotherapy, allogeneic, or autologous stem-cell
      transplantation as postremission treatment for children with very high risk acute
      lymphoblastic leukemia: PETHEMA ALL-93 Trial.
AB  - PURPOSE: The optimal postremission therapy for children with very high-risk (VHR)
      acute lymphoblastic leukemia (ALL) is not well established. This randomized trial
      compared three options of postremission therapy: chemotherapy and allogeneic or
      autologous stem-cell transplantation (SCT). PATIENTS AND METHODS: All 106 VHR-ALL
      patients received induction with five drugs followed by intensification with
      three cycles of chemotherapy. Patients in complete remission (CR) with an HLA
      identical family donor were assigned to allogeneic SCT (n = 24) and the remaining
      were randomly assigned to autologous SCT (n = 38) or to delayed intensification
      followed by maintenance chemotherapy up to 2 years in CR (n = 38). RESULTS:
      Overall, 100 patients achieved CR (94%). With a median follow-up of 6.5 years, 5
      year disease-free survival (DFS) and overall survival (OS) probabilities were 45%
      (95% CI, 37% to 54%) and 48% (95% CI, 40% to 57%), respectively. The three groups
      were comparable in the main pretreatment ALL characteristics. Intention-to-treat
      analysis showed no differences for donor versus no donor in DFS (45%; 95% CI, 27%
      to 65% v 45%; 95% CI, 37% to 55%) and OS (48%; 95% CI, 30% to 67% v 51%; 95% CI,
      43% to 61%), as well as for autologous SCT versus chemotherapy comparisons (DFS:
      44%; 95% CI, 29% to 60% v 46%; 95% CI, 32% to 62%; OS: 45%; 95% CI, 31% to 62% v
      57%; 95% CI, 43% to 73%). No differences were found within the different
      subgroups of ALL and neither were differences observed when the analysis was made
      by treatment actually performed. CONCLUSION: This study failed to prove that,
      when a family donor is available, allogeneic SCT produces a better outcome than
      autologous SCT or chemotherapy in children with VHR-ALL.

PMID- 17194903
TI  - Pharmacokinetics of gemcitabine in Japanese cancer patients: the impact of a
      cytidine deaminase polymorphism.
AB  - PURPOSE: Gemcitabine is rapidly metabolized to its inactive metabolite, 2',2'
      difluorodeoxyuridine (dFdU), by cytidine deaminase (CDA). We previously reported
      that a patient with homozygous 208A alleles of CDA showed severe adverse
      reactions with an increase in gemcitabine plasma level. This study extended the
      investigation of the effects of CDA genetic polymorphisms on gemcitabine
      pharmacokinetics and toxicities. PATIENTS AND METHODS: Genotyping of CDA was
      performed by a direct sequencing of DNA obtained from the peripheral blood of
      Japanese gemcitabine-naive cancer patients (n = 256). The patients recruited to
      the association study received a 30-minute intravenous infusion of gemcitabine at
      a dose of either 800 or 1,000 mg/m2, and eight blood samples were periodically
      collected (n = 250). Plasma levels of gemcitabine and dFdU were measured by high
      performance liquid chromatography. Plasma CDA activities toward cytidine and
      gemcitabine were also measured (n = 121). RESULTS: Twenty-six genetic variations,
      including 14 novel ones and two known nonsynonymous single nucleotide
      polymorphisms (SNPs), were detected. Haplotypes harboring the nonsynonymous SNPs
      79A>C (Lys27Gln) and 208G>A (Ala70Thr) were designated *2 and *3, respectively.
      The allelic frequencies of the two SNPs were 0.207 and 0.037, respectively.
      Pharmacokinetic parameters of gemcitabine and plasma CDA activities significantly
      depended on the number of haplotype *3. Haplotype *3 was also associated with
      increased incidences of grade 3 or higher neutropenia in the patients who were
      coadministered fluorouracil, cisplatin, or carboplatin. Haplotype *2 showed no
      significant effect on gemcitabine pharmacokinetics. CONCLUSION: Haplotype *3
      harboring a nonsynonymous SNP, 208G>A (Ala70Thr), decreased clearance of
      gemcitabine, and increased incidences of neutropenia when patients were
      coadministered platinum-containing drugs or fluorouracil.

PMID- 17194904
TI  - Screening for coronary artery disease after mediastinal irradiation for Hodgkin's
      disease.
AB  - PURPOSE: Incidental cardiac irradiation during treatment of thoracic neoplasms
      has increased risks for subsequent acute myocardial infarction or sudden cardiac
      death. Identifying patients who have a high risk for a coronary event may
      decrease morbidity and mortality. The objective of this study was to evaluate
      whether stress imaging can identify severe, unsuspected coronary stenoses in
      patients who had prior mediastinal irradiation for Hodgkin's disease. PATIENTS
      AND METHODS: We enrolled 294 outpatients observed at a tertiary care cancer
      treatment center after mediastinal irradiation doses 35 Gy for Hodgkin's disease
      who had no known ischemic cardiac disease. Patients underwent stress
      echocardiography and radionuclide perfusion imaging at one stress session.
      Coronary angiography was performed at the discretion of the physician. RESULTS:
      Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest,
      suggesting prior myocardial injury. During stress testing, 42 patients (14%)
      developed perfusion defects (n = 26), impaired wall motion (n = 8), or both
      abnormalities (n = 8). Coronary angiography showed stenosis 50% in 22 patients
      (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients
      (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three
      patients developed coronary events during a median of 6.5 years of follow-up,
      with 10 acute myocardial infarctions (two fatal). CONCLUSION: Stress-induced
      signs of ischemia and significant coronary artery disease are highly prevalent
      after mediastinal irradiation in young patients. Stress testing identifies
      asymptomatic individuals at high risk for acute myocardial infarction or sudden
      cardiac death.

PMID- 17194905
TI  - Outcome after radiotherapy alone for metastatic spinal cord compression in
      patients with oligometastases.
AB  - PURPOSE: To investigate outcome and prognosis of metastatic spinal cord
      compression (MSCC) patients with oligometastatic disease treated with
      radiotherapy alone. PATIENTS AND METHODS: Oligometastatic disease was defined as
      involvement of three or fewer vertebrae and lack of other bone or visceral
      metastases. Five hundred twenty-one patients with oligometastatic disease and
      MSCC were evaluated for functional outcome, ambulatory status, local control of
      MSCC, and survival. Furthermore, seven potential prognostic factors were
      investigated. RESULTS: Motor function improved in 40% (n = 207), remained stable
      in 54% (n = 279), and deteriorated in 7% (n = 35) of patients. Fifty-eight (54%)
      of 107 nonambulatory patients became ambulatory, and 388 (94%) of 414 ambulatory
      patients remained ambulatory. Improved functional outcome was significantly
      associated with tumor type and slower development of motor deficits (> 14 days).
      Local control at 1, 2, and 3 years was 92%, 88%, and 78%, respectively. Improved
      local control was significantly associated with long-course radiotherapy.
      Survival at 1, 2, and 3 years was 71%, 58%, and 50%, respectively. Better
      survival was significantly associated with tumor type, ambulatory status, slower
      development of motor deficits, and long-course radiotherapy. Patients who
      developed motor deficits slowly (onset > 14 days before initiating treatment)
      were further analyzed. In this subgroup, the best results were observed for
      myeloma/lymphoma and breast cancer patients. No patient had progression of motor
      deficits. One hundred percent (myeloma/lymphoma) and 99% (breast cancer) of
      patients were ambulatory after radiotherapy. One-year local control was 100% and
      98%, 1-year survival was 94% and 89%. CONCLUSION: Given the limitations of a
      retrospective review, improved outcome of patients with oligometastatic MSCC was
      associated with myeloma/lymphoma and breast cancer, slower development of motor
      deficits, and a more prolonged course of radiation.

PMID- 17194906
TI  - Incidence of venous thromboembolism and the impact on survival in breast cancer
      patients.
AB  - PURPOSE: The incidence of venous thromboembolism (VTE) and the risk factors
      associated with development of VTE have not been reported in a large population
      based study of breast cancer patients. PATIENTS AND METHODS: The California
      Cancer Registry was merged with the Patient Discharge Data Set, and the number of
      VTE events determined among patients diagnosed between 1993 and 1999. RESULTS:
      Among 108,255 patients with breast cancer, the 2-year cumulative VTE incidence
      was 1.2%, with a rate of 1.2 and 0.6 events/100 patient-years during the first
      and second half-year, respectively. The 1-year incidence of VTE was significantly
      increased compared with the general population (standardized incidence ratio of
      VTE, 4.2; 95% CI, 3.9 to 4.4). In a multivariate model, significant predictors of
      developing VTE within 2 years were: age (hazard ratio [HR], 2.0 if > 75 years v <
      45; 95% CI, 1.6 to 2.6), the number of chronic medical comorbidities (HR, 2.9 if
      3 v 0; 95% CI, 2.4 to 3.5), and advancing cancer stage (HR, 6.3; 95% CI, 5.3 to
      7.5 for metastatic v local disease). In multivariate models, VTE was a
      significant predictor of decreased 2-year survival (HR, 2.3; 95% CI, 2.1 to 2.6)
      and when stratified by initial cancer stage, the effect was highest in patients
      with localized (HR, 5.1; 95% CI, 3.6 to 7.1) or regional stage (HR, 3.5; 95% CI,
      2.5 to 4.8) cancer compared with patients with metastatic disease (HR, 1.9; 95%
      CI, 1.5 to 2.4). CONCLUSION: Approximately 1% of breast cancer patients developed
      VTE within 2 years, with the highest incidence in the first 6 months after
      diagnosis. Metastatic disease and comorbidities were the strongest predictors.
      The diagnosis of VTE was associated with a higher risk of death within 2 years.

PMID- 17194907
TI  - Phase II study of neoadjuvant androgen deprivation followed by external-beam
      radiotherapy with 9 months of androgen deprivation for intermediate- to high-risk
      localized prostate cancer.
AB  - PURPOSE: To evaluate the toxicity and efficacy of individualized neoadjuvant
      androgen deprivation (AD) to maximal response followed by external beam
      radiotherapy (RT) with continued AD for a total of 9 months in a prospective
      phase II trial. PATIENTS AND METHODS: One hundred twenty-three patients received
      a total of 9 months of flutamide and luprolide combined with RT. RT initiation
      was individualized to begin after maximum response to AD as assessed by monthly
      digital rectal examination and prostate-specific antigen (PSA). The neoadjuvant
      phase was restricted to no more than 6 months. RESULTS: Median time to initiation
      of RT was 4.7 months. Indications to begin RT (and their rates) were undetectable
      PSA (28%), PSA unchanged from one month to the next (46%), PSA rising from one
      month to the next (10%), 6 months of AD (14%), and other (2%). Five-year outcomes
      were biochemical disease-free survival, (DFS) 63% +/- 7%; clinical DFS, 75% +/-
      5%; cancer-specific survival, 99% +/- 1%; and overall survival, 89% +/- 3%.
      Patients initiating RT after 6 months of AD had significantly lower biochemical
      and clinical DFS. Those patients whose testosterone recovered to normal after
      completion of AD had a significantly superior survival rate. Of those patients
      potent before treatment, 65% remained so at last follow-up. CONCLUSION: The
      combination of 9 months of AD and RT, with initiation of RT individualized on the
      basis of maximum response to AD, achieves disease control rates comparable with
      past studies, while preserving potency in many patients. Further studies are
      warranted to determine the optimal combination of AD and RT in this patient
      population.

PMID- 17194908
TI  - Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in
      previously treated germ cell tumors.
AB  - PURPOSE: To evaluate the optimal dose of carboplatin as well as the efficacy and
      tolerability of sequential, dose-intense chemotherapy with paclitaxel and
      ifosfamide followed by carboplatin and etoposide (TICE) plus peripheral-blood
      stem-cell (PBSC) support in patients with germ cell tumors (GCT) who are likely
      to experience treatment failure with conventional-dose salvage treatment. This
      prospective trial followed a similarly designed report of TICE, which used a
      different means of carboplatin dosing. PATIENTS AND METHODS: The 48 patients
      entered onto this trial had progressive GCT and unfavorable prognostic features
      after chemotherapy. Two cycles of paclitaxel plus ifosfamide were administered
      with leukapheresis, followed by three cycles of carboplatin plus etoposide with
      reinfusion of PBSC. RESULTS: Twenty-three (49%) of 47 assessable patients
      achieved a complete response (CR) to chemotherapy. An additional three patients
      (6%) achieved a CR to chemotherapy and surgery. The CR rate was 55%. Six patients
      experienced relapse, but 24 patients (51%) are alive and free of disease at a
      median follow-up time of 40 months. Four patients who experienced relapse or
      achieved an incomplete response were rendered disease free by salvage surgical
      resection. When combined with results of the prior trial of similar design, TICE
      chemotherapy yielded an overall CR of 56% (n = 84), with 50% of patients alive
      with no evidence of disease. CONCLUSION: TICE is an effective and tolerable dose
      intense treatment for patients with previously treated metastatic GCT who have a
      poor predicted outcome to conventional-dose salvage chemotherapy.

PMID- 17194909
TI  - Volume-based referral for cancer surgery: informing the debate.
AB  - PURPOSE: Mounting evidence suggests a relationship between hospital volume and
      outcomes after major cancer surgery; however, the absolute benefits of volume
      based referral on a national basis are unclear. PATIENTS AND METHODS: Data from
      the Nationwide Inpatient Sample were used to measure the likelihood of operative
      mortality and a prolonged length of stay (LOS) after six cancer surgeries
      (prostatectomy, cystectomy, esophagectomy, pancreatectomy, pneumonectomy, and
      liver resection) between 1993 and 2003. Using sampling weights, the adjusted
      likelihood of the outcomes was used to calculate the number of lives saved (or
      prolonged LOS avoided) in the United States. RESULTS: The magnitude of the volume
      operative mortality effect varied from an adjusted odds ratio (OR) of 1.3 (95%
      CI, 0.8 to 2.3) for cystectomy to 4.9 (95% CI, 2.4 to 10.1) for pancreatectomy.
      After accounting for varying rates of procedure utilization, the lives saved per
      100 surgeries regionalized ranged from 0.2 (95% CI, 0.12 to 0.24 lives saved) for
      prostatectomy to 9.2 (95% CI, 6.7 to 10.4 lives saved) for pancreatectomy. The
      volume-prolonged LOS effect varied from an adjusted OR of 0.9 (95% CI, 0.5 to
      1.6) for liver resection to 4.8 (95% CI, 3.5 to 6.7) for prostatectomy. After
      accounting for procedure use, the number of prolonged hospitalizations avoided
      ranged from -1.7 (95% CI, -11.3 to 3.6 hospitalizations) to 14.3 (95% CI, 12.9 to
      15.4 hospitalizations) per 100 surgeries regionalized for liver resection and
      prostatectomy, respectively. CONCLUSION: For patients undergoing major cancer
      surgery, the benefits of volume-based referral depend on the interplay between
      procedure utilization, the magnitude of effect, and the outcome chosen.

PMID- 17194910
TI  - Cancer rates after year 2000 significantly decrease in children with perinatal
      HIV infection: a study by the Italian Register for HIV Infection in Children.
AB  - PURPOSE: To evaluate the impact of highly active antiretroviral therapy (HAART)
      on cancer incidence in HIV-infected children throughout a 20-year period.
      PATIENTS AND METHODS: An observational population study was conducted on 1,190
      perinatally HIV-infected children enrolled onto the Italian Register for HIV
      Infection in Children from 1985 to 2004 and never lost to follow-up (total
      observation time, 10,037.66 years). Cancer rates were calculated in the pre-HAART
      (1985 to 1995), early HAART (1996 to 1999), and late HAART (2000 to 2004) periods
      and compared using Poisson regression adjusted for age. The proportion of HAART
      treated children increased from 4.1% in 1996 to 60.4% in 1999 and to 81.5% in
      2004. In the same time frame, the proportion of children receiving HAART for at
      least 2 years increased from 3.1% to 77.0%. RESULTS: Overall, 35 cancers
      occurred. Cancer rates were 4.49 (95% CI, 2.37 to 6.64), 4.09 (95% CI, 1.68 to
      6.50), and 0.76 (95% CI, 0.00 to 1.80) per 1,000 children per year in 1985 to
      1995, 1996 to 1999, and 2000 to 2004, respectively. Notably, there was no
      significant difference comparing the periods from 1985 to 1995 and 1996 to 1999
      (P = .081). By contrast, cancer rates were significantly lower in the period from
      2000 to 2004 than in 1996 to 1999 (P < .0001). Results were confirmed by
      separately analyzing data from children observed from birth (P = .418 for 1985 to
      1995 v 1996 to 1999; P = .001 for 1996 to 1999 v 2000 to 2004). CONCLUSION:
      Dramatically reduced cancer rates were observed only in the late HAART period in
      parallel to the increasing proportion of children receiving HAART therapy.

PMID- 17194911
TI  - Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage
      III colon cancer: a planned safety analysis in 1,864 patients.
AB  - PURPOSE: To report the results of a planned safety analysis from a phase III
      trial comparing capecitabine plus oxaliplatin (XELOX) with bolus
      fluorouracil/leucovorin (FU/LV) as adjuvant therapy for stage III colon cancer.
      PATIENTS AND METHODS: Patients with stage III colon carcinoma were randomly
      assigned to receive either XELOX (intravenous oxaliplatin plus oral capecitabine;
      3-week cycle for eight cycles) or standard intravenous bolus FU/LV administered
      as the Mayo Clinic (Mayo; Rochester, MN) or Roswell Park (RP; Buffalo, NY)
      regimen for a similar length of time. A total of 1,886 patients were randomly
      assigned. RESULTS: The safety population comprised 1,864 patients, of whom 938
      received XELOX and 926 received FU/LV. Most treatment-related adverse events
      (AEs) occurred at similar rates in both treatment arms. However, patients
      receiving XELOX experienced less all-grade diarrhea, alopecia, and more
      neurosensory toxicity, vomiting, and hand-foot syndrome than those patients
      receiving FU/LV. Compared with Mayo, XELOX showed fewer grade 3/4 hematologic AE
      and more grade 3/4 gastrointestinal AE. Compared with RP, XELOX showed less grade
      3/4 gastrointestinal AE and more grade 3/4 hematologic AE. As expected grade 3/4
      neurosensory toxicity and grade 3 hand-foot syndrome were higher with XELOX.
      Treatment-related mortality within 28 days from the last study dose was 0.6% in
      the XELOX group and 0.6% in the FU/LV group. CONCLUSION: XELOX has a manageable
      tolerability profile in the adjuvant setting. Efficacy data will be available
      within the next 24 months.

PMID- 17194912
TI  - Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer.
AB  - PURPOSE: To evaluate the activity and safety of preoperative radiotherapy (RT)
      and concurrent capecitabine and oxaliplatin (XELOX-RT) plus four cycles of
      adjuvant XELOX in patients with rectal cancer. PATIENTS AND METHODS: One hundred
      ten patients with T3/T4 or N+ rectal cancer were entered onto the trial in 11
      investigator sites and received preoperative RT (50.4 Gy in 28 fractions).
      Capecitabine was administered concurrently at 1,650 mg/m2 on days 1 to 14 and 22
      to 35, and oxaliplatin was administered at 50 mg/m2 on days 1, 8, 22, and 29.
      Surgery was scheduled 4 to 6 weeks after completion of XELOX-RT. Four cycles of
      adjuvant XELOX (capecitabine 1,000 mg/m2 bid on days 1 to 14; oxaliplatin 130
      mg/m2 on day 1) were administered. The main end points were activity as assessed
      by the pathologic complete response (pCR) rate and the feasibility of
      postoperative XELOX chemotherapy. RESULTS: After XELOX-RT, 103 of 104 eligible
      patients underwent surgery; pCR was achieved in 17 patients (16%), one patient
      had ypT0N1 disease, and 53 patients showed tumor regression of more than 50% of
      the tumor mass. R0 resections were achieved in 95% of patients, and sphincter
      preservation was accomplished in 77%. Full-dose preoperative XELOX-RT was
      administered in 96%. Grade 3 or 4 diarrhea occurred in 12% of patients.
      Postoperative complication occurred in 43% of patients. Sixty percent of patients
      received all four cycles of adjuvant XELOX, with sensory neuropathy (18%) and
      diarrhea (12%) being the main grade 3 or 4 toxicities. CONCLUSION: Preoperative
      XELOX-RT plus four cycles of adjuvant XELOX is an active and feasible treatment.
      This regimen is proposed for phase III evaluation comparing standard fluorouracil
      based treatment with XELOX- based multimodality treatment.

PMID- 17194913
TI  - Peer mentoring and survivors' stories for cancer patients: positive effects and
      some cautionary notes.

PMID- 17194914
TI  - Maternal-fetal status of copper, iron, molybdenum, selenium, and zinc in obese
      pregnant women in late gestation.
AB  - Obesity is well known to be a contributory risk factor for several disease
      states, including diabetes mellitus. Further, obese women are more prone to have
      babies born with congenital abnormalities. Paucity of data on maternal-fetal
      disposition of essential trace elements in obese pregnancies prompted us to
      undertake this study. Maternal venous and umbilical arterial and venous samples
      were collected from obese patients (body mass index >30) and control pregnant
      women (body mass index <25) at time of spontaneous delivery or cesarean sections
      and concentrations of essential trace elements such as Cu, Fe, Mo, Se, and Zn
      determined in various samples by atomic absorption spectrophotometry. Activities
      of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and total
      antioxidant activity in maternal and umbilical blood were assessed using
      appropriate reagent kits. Maternal-fetal disposition and exchange parameters of
      elements studied were assessed using established criteria. Concentrations of Cu,
      Fe, Mo, Se, and Zn in the serum of control pregnant women at time of delivery
      averaged 2232.6, 2398.1, 10.9, 108.9, and 661.9 microg/L respectively, whereas in
      the obese group, the values of the above elements averaged 2150.3, 2446.8, 12.6,
      96.8, and 838.9 microg/L respectively. Umbilical vein/maternal vein ratios of Cu,
      Fe, Mo, Se, and Zn in the control group averaged 0.29, 1.93, 1.06, 0.76, and
      1.12, respectively, whereas in the obese group, their fetal-maternal ratios
      averaged 0.32, 2.23, 1.06, 0.78, and 1.53, respectively. The Cu : Zn ratio in the
      maternal vein of the obese group (3.60 +/- 0.20) was significantly lower
      (Student's t-test; p < 0.05) than that of the controls (2.50 +/- 0.19); however,
      Cu : Fe ratio (1.04 +/- 0.08 vs 1.02 +/- 0.09) was not significantly different
      (Student's t-test; p > 0.05) in the two groups. Varying differences were noted in
      the case of antioxidant enzyme activities between the control and study groups.
      We conclude that obesity is associated with alterations in maternal-fetal
      disposition of some essential trace elements and antioxidant enzyme status and
      that these alterations could pose a potential health risk for the mother as well
      as the fetus.

PMID- 17194915
TI  - Serum copper concentration in adults with acute, uncomplicated falciparum malaria
      infection.
AB  - Serum copper concentration was measured in 80 adult patients (40 males and
      females each; age range: 18-40 yr) presenting with acute, uncomplicated
      falciparum malaria infection and a control group of 20 age-matched, healthy
      individuals. The mean serum copper concentration was 109.0 +/- 40.0 microg/dL in
      healthy individuals. Both male and female patients were found to have a
      significantly decreased serum copper concentration (p < 0.05). In the male
      patients, the mean serum copper concentration decreased by 33.95%, whereas it
      dropped by 38.53% in their female counterparts. A compromised enzymatic
      antioxidant defense capability, particularly superoxide dismutase (SOD) activity,
      has been reported in patients with falciparum malaria infection. Because SOD
      activity is dependent on copper, the ineffective SOD activity can be related to
      the decrease in the concentration of copper during the infection. Low serum
      copper can also contribute to the ineffective immune response of the host to the
      antigenic challenge of the falciparum parasite because copper is also important
      for normal immune function.

PMID- 17194916
TI  - Selenium and zinc in patients with acute and chronic uveitis.
AB  - Patients with chronic inflammation often show decreased serum levels of trace
      elements. This study aimed to investigate serum levels of selenium and zinc in
      patients with uveitis. Twenty-four patients (13 female, 11 male) with a mean age
      of 40.6 +/- 15.5 yr were included in this study. According to their underlying
      disease, they were divided into acute (n = 13) or chronic (n = 11) uveitis.
      Selenium and zinc determination was performed by atomic absorption spectroscopy
      in EDTA blood samples. Patients with acute or first-time uveitis showed selenium
      and zinc concentrations within the normal range. In contrast to this, patients
      with chronic recurrent uveitis tend to result in decreased selenium and zinc
      levels. Especially selenium showed a remarkable reduction in serum concentration
      below the normal range. Furthermore, there was a tendency to decreased trace
      element concentrations with increasing age. A sex dependency could not been
      found. Especially patients with chronic, recurring uveitis show remarkable
      decreased selenium concentration in the EDTA-blood. Further studies should
      investigate possible positive effects of therapeutic selenium and zinc
      supplementation in patients with chronic, recurrent uveitis.

PMID- 17194917
TI  - Exogenous zinc improves blood fluidity but has no effect on the mechanisms of
      vascular response to acetylcholine iontophoresis in humans.
AB  - Recent findings in cellular signaling function of zinc through the mobilization
      intracellular calcium or by inducing ATP release suggest that extracellular zinc
      plays an important role in many physiological functions. However, such an
      extracellular signaling action of zinc for most cells is not known. Therefore, we
      investigated whether zinc plays any role in endothelium- dependent acetylcholine
      (ACh)-induced vasodilatation in microvascular beds. Transdermal iontophoresis was
      used to transport ACh through the forearm skin and cutaneous perfusion was
      measured using a laser Doppler flowmeter (LDF). Experiments were repeated using
      (1) zinc instead of ACh to test the effect of zinc ions alone and (2) concomitant
      iontophoresis of ACh and zinc to explore the effect of zinc on ACh-induced
      vasodilatation. Although zinc augments blood flow, curve-fitting to LDF signals
      indicate that zinc has no effect on the neural and endothelial component of ACh
      induced vasodilatation. Additionally, no effect of Zn2+ on blood flow was found
      during its iontophoresis alone. Therefore, it is suggested from the Fourier
      analysis of LDF signals that the Zn+ might influence blood fluidity by its action
      on red blood cells deformability/ aggregability during a high-blood-flow
      condition, which might, in turn, decrease blood viscosity and improve blood flow
      in vivo.

PMID- 17194918
TI  - Effects of dietary arsenic levels on serum parameters and trace mineral
      retentions in growing and finishing pigs.
AB  - This experiment was conducted to investigate the effect of dietary arsenic (As)
      levels on growth performance, serum biochemistry, and the retention of iron,
      copper, and zinc in tissues of growing and finishing pigs. Ninety-six crossbred
      pigs were randomly allotted to four dietary treatments. The corn-soybean basal
      diets were supplemented with 0, 10, 20, and 30 mg As/kg. Arsenic trioxide was
      used as the arsenic source. The feeding experiment lasted for 78 d. The results
      showed that the high arsenic diet decreased average daily gain (ADG) (p<0.05) and
      increased feed gain ratio (F/G) (p<0.05). Arsenic intake significantly increased
      (p<0.05) serum gamma-gultamyltransferase (GGT), glutamic-pyruvic transaminase
      (GPT), and alkaline phosphatase (ALP) activities, and decreased (p<0.05) total
      protein, urea nitrogen, creatinine, and triglycerides. Glutamic-oxalacetic
      transaminase (GOT) activity, albumin, and cholesterol were not affected (p>0.05).
      Arsenic feeding elevated (p<0.05) liver and kidney copper concentration, but
      reduced (p<0.05) copper concentration in heart, bile, and lymphaden of intestine
      mesentery. There were increases in iron levels in liver, bile, spleen, thymus,
      and pancreas in pigs fed the high As diets (p<0.05), but iron contents in kidney,
      heart, and serum were decreased by the arsenic treatment (p<0.05). Zinc
      concentrations were increased (p<0.05) in liver, kidney, and thymus of pigs with
      arsenic treatment, but decreased (p<0.05) in bile and lymphaden of intestine
      mesentery. This study suggested that high dietary As levels could alter serum
      biochemical parameters and the retention of copper, iron, and zinc in the viscera
      of growing and finishing pigs.

PMID- 17194919
TI  - Effects of different proteins on the metabolism of Zn, Cu, Fe, and Mn in rats.
AB  - Many factors are known to influence trace element metabolism and one of them is
      dietary protein. The present study examines the effects of casein, soybean
      protein, and peanut protein on the metabolism of the Zn, Cu, Fe, and Mn in
      growing rats. The results showed that Zn, Fe, and Mn excretions in the feces of
      peanut protein-fed rats (PPFRs) were similar to that of casein-fed rats (CPFRs)
      (p > 0.05), whereas all of the Zn, Cu, Fe, and Mn excretions in the urine of
      PPFRs were significantly higher than that of CPFRs (p < 0.05), but its apparent
      absorption rate (AAR) of Cu, Fe and its apparent retention rate (ARR) of Cu were
      all higher than that of CPFRs (p < 0.05). Hepatic Zn content of soybean protein
      fed rats (SPFRs) was higher than that of CPFRs and PPFRs (p < 0.05 respectively)
      and serum, renal, and femoral Cu contents of SPFRs were significantly lower;
      however, hepatic Cu, and renal Mn contents were significantly higher than that of
      CPFRs (p < 0.05, respectively); The hepatic Fe content of SPFRs was significantly
      higher than that of CPFRs and PPFRs (p < 0.01, respectively). To sum up, compared
      to casein, soybean protein might be a good dietary source to make up for Zn and
      Fe deficiency, and also peanut protein to make up for Cu and Fe deficiency.

PMID- 17194920
TI  - Oxidative stress in mice: effects of dietary corn oil and iron.
AB  - The aim of this study was to analyze the effect of high dietary Fe on liver
      antioxidant status in mice fed a corn-oil-enriched diet. Male Balb/c mice were
      fed for 3 wk with a standard diet enriched with 5% by weight of corn oil with
      adequate Fe (FCO diet) or supplemented with 1% carbonyl Fe (FCOFe diet). The
      control group was fed a standard diet. The high-Fe diet induced a twofold
      increase of hepatic Fe level. However, an increase of thymic Fe level has been
      induced solely by dietary fat. The hepatic copper (Cu) level slightly decreased
      in the FCO diet. In the spleen, the high-Fe diet-induced increase of Fe level was
      negatively correlated with the Cu level. The antioxidant status was influenced by
      both dietary fat and Fe. Mice fed corn-oil-enriched diets had a higher
      concentration of thiobarbituric acid-reactive substances (TBARS), with a greater
      increase in the FCOFe diet. Fatty acid analysis showed decreased n-3 and n-6/n-3
      ratio, particularly in the FCOFe diet. Hepatic Cu/Zn superoxide dismutase (CuZn
      SOD) activity was decreased in FCO diet, and Fe supplementation caused a further
      decrease in the enzyme activity. These results suggest that feeding with corn oil
      enriched diet increases oxidative damage by decreasing antioxidant enzyme
      defense. The high-Fe diet additionally affects the antioxidant defense system,
      further increasing the tissue's susceptibility to lipid peroxidation.
      Additionally, both corn-oil- and Fe-enriched diets have increased the Cu
      requirement in mice.

PMID- 17194921
TI  - Effect of lanthanum ions (La3+) on ferritin-regulated antioxidant process under
      PEG stress.
AB  - The physiological effects of lanthanum(III) ions on the ferritin-regulated
      antioxidant process were studied in wheat (Triticum aestivum L.) seedlings under
      polyethylene glycol (PEG) stress. Treatment with 0.1 mM La3+ resulted in
      increased levels of chlorophyll, carotenoid, proline, ascorbate, and reduced
      glutathione. The activities of superoxide dismutase, catalase, ascorbate
      peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase,
      glutathione reductase, and peroxidase were also increased after La3+ treatment.
      Treatment with La3+ seems to enhance the capacity of the reactive oxygen species
      scavenging system, affect the Fe2+ and Fe3+ electron-transfer process in
      ferritin, and restrain the formation of hydroxyl radical (OH.), alleviating the
      oxidative damage induced by PEG stress.

PMID- 17194922
TI  - Longitudinal study of serum zinc and copper levels in hemodialysis patients and
      their relation to biochemical markers.
AB  - A 6-mo longitudinal study of 48 hemodialysis patients (HPs) with chronic renal
      failure was performed. Three blood samplings were done. Samples of whole blood
      from each patient were collected during hemodialysis sessions after passing
      through the artificial kidney. Zinc and copper levels were measured by atomic
      absorption spectrometry. Additionally, 36 biochemical indexes were evaluated
      during the study. Fifty-two healthy matched controls were also considered. Mean
      serum zinc and copper concentrations in HPs were significantly decreased (Zn) and
      increased (Cu), when compared with healthy controls (p < 0.01). Zinc
      concentrations found in the first and second blood samplings from patients were
      significantly lower than those measured for the third sampling (p < 0.01). The
      etiology of chronic renal failure influenced the statistically serum Zn levels of
      patients (p < 0.05). Serum copper levels of HPs were significantly diminished by
      the existence of secondary associated diseases (p < 0.01). Uric acid and
      parathyroid hormone, and total-cholesterol and glutamic-pyruvic-transaminase
      levels were significantly (p < 0.05) and linearly related with serum zinc and
      copper concentrations, respectively. From all of indexes, creatinine, direct
      bilirubin, magnesium, calcium, parathyroid hormone, transferrin, and albumin were
      statistically modified along the longitudinal study (p < 0.05). Transferrin serum
      levels were significantly diminished in the third blood sampling, indicating the
      tendency toward anemia in the patients. This result is reinforced by low levels
      of biochemical and hematological indexes related with iron body staus.

PMID- 17194923
TI  - Gender-specific determinants of goiter.
AB  - Despite the strong implications of differences between females and males in the
      risk of goiter, gender-specific issues have not been extensively addressed in
      investigations of goiter prevalence. The objective of our analysis was to
      investigate the gender-specific determinants of goiter. Between April 2001 and
      April 2002. A total of 853 healthy employees from 4 institutions in the western
      part of Germany between 18 and 68 yr of age were examined by ultrasound of the
      neck to determine the thyroid volume. Information on sex, age, daily use of
      iodized salt, the history of goiter in the first-degree relatives, type and
      amount of smoking, oral contraceptives, and number of pregnancies were assessed
      by standardized questionnaires. Gender-specific predictors of goiter prevalence
      were assessed by multivariate logistic regression. The overall prevalence of
      goiter among study subjects was 204/853 (23.9%). Goiter was present in 80 out of
      370 females (21.6%) vs 124/483 (25.7%) in males. In general, smoking (p <
      0.0001), increasing age (p < 0.0001), and lack of daily intake of iodized salt (p
      = 0.004) were associated with goiter prevalence, but not sex (p = 0.39) and
      family history of goiter (p = 0.16). In 370 females, parity (p = 0.004) and lack
      of daily intake of iodized salt (p = 0.01) were the major determinants for
      goiter, whereas age (p = 0.18), oral contraceptives (p = 0.82), family history of
      goiter (p = 0.33), and smoking (p = 0.09) did not affect goiter prevalence. In
      483 males, smoking (p < 0.0001) and age (p < 0.001) affected goiter prevalence,
      but not family history of goiter (p = 0.39), and the iodine status failed just to
      reach the significant level (p = 0.08) in this analysis. Gender-specific
      determinants of goiter are parity and iodine status in females and smoking and
      increasing age in males.

PMID- 17194924
TI  - Regulative mechanism of Ce3+ relieves DNA damage caused by Cd2+ in the kidney of
      silver crucian carp.
AB  - The mechanism of Cd2+ on the DNA cleavage and Ce3+ on the DNA repair in the
      kidney of silver crucian carp (Carassius auratus gibelio) is investigated by
      agarose gel electrophoresis methods and assaying biochemical indexes. It proves
      that Cd2+ induces the classical laddering degradation of DNA in vivo, but DNA
      cleavage is repaired after injecting with a low Ce3+ concentration under various
      Cd2+ concentrations. The DNA cleavage caused by Cd2+ is the result of the
      activation of deoxyribonuclease (DNase) and accumulation of reactive oxygen
      species (ROS), and Cd2+ destroys the antioxidant system, which diminishes the
      activities of superoxide dismutase, catalase, and peroxidase, and the increase of
      the lipid peroxidation (LPO) level. However, Ce3+ could inhibit activation of
      Cd2+ on DNase activity, relieve inhibition of Cd2+ on activities of the
      antioxidant enzyme, and diminish ROS accumulation. The results show that Ce3+
      could relieve the toxicity of Cd2+ to silver crucian carp.

PMID- 17194926
TI  - Blood and urine iodine levels in patients with gastric cancer.
AB  - In this study, we aimed to investigate whether there is any relationship between
      gastric cancer and iodine concentrations in blood and urine in the northeast
      Anatolia region, where iodine deficiency is common. A total of 56 patients,
      diagnosed as gastric cancer and 25 healthy volunteers were included in the study.
      The methods used were based on the Sandell-Kolthoff reaction. The urine iodine
      concentration (UIC) and serum protein-bound iodine (PBI) levels were higher in
      patients with gastric cancer compared with healthy control subjects. The UIC in
      stage IV was higher than all other stages and the control group. The UIC was
      higher in stages III and IV compared with stages I and II. However, serum PBI
      levels in stage III were higher compared with stages I and II and also control
      group. The serum PBI level in stage IV was higher than stage II and the control
      group. In the patient and control groups, there were no significant differences
      in serum PBI and UIC with regard to age or sex. Our results suggested that
      urinary and blood iodine concentration might be a useful marker for following the
      disease.

PMID- 17194927
TI  - Effects of trichophytosis on serum zinc levels in calves.
AB  - The purpose of this study was to determine the zinc levels in calves with
      trichophytosis and to research the importance of zinc for fungi. The sera of 20
      calves with trichophytosis and 10 healthy calves were used in this study. Zinc
      levels of the sera were measured by the atomic absorption spectrophotometer
      method. Serum zinc levels of diseased and healthy animals were found to be 42.0+/
      16.6 microg/dL and 75.8+/-5.9 microg/dL, respectively. Serum zinc levels of
      diseased calves were lower than healthy ones and this difference were found to be
      important statistically (p<0.001), whereas there is no statistical difference on
      the levels of lymphocyte, monocyte, granulocyte, erythrocyte, hemoglobin,
      hematocrit, and mean corpuscular volume between groups. These parameters were not
      influenced by low zinc levels.

PMID- 17194925
TI  - Decrease of trace elements in erythrocytes and plasma after removal of dental
      amalgam and other metal alloys.
AB  - The objective of this study was to determine the concentration changes of 13
      elements in erythrocytes and plasma after the removal of dental amalgam and other
      metal alloys. Blood samples from 250 patients were collected, separated into
      erythrocytes and plasma, and analyzed by inductively coupled plasma-mass
      spectrometry. The 250 patients were divided into 3 groups (Negative, Zero, and
      Positive) depending on their estimation of quality of life in an earlier study.
      Magnesium in plasma, selenium and mercury in plasma, and erythrocytes showed
      decreased concentrations after amalgam removal in all groups (p < 0.05). Titanium
      in plasma, copper in plasma, and erythrocytes and zinc in plasma exhibited
      decreased concentrations after amalgam removal in the Negative and Positive
      groups (p < 0.05). Silver in plasma and gold in erythrocytes decreased in the
      Zero and Positive groups after amalgam removal (p < 0.05). Copper in erythrocytes
      and silver and gold in plasma showed higher concentrations after amalgam removal
      in the Negative compared to the Positive group (p < 0.05), suggesting that
      patients in the Negative group excrete metals slowly. Moreover, the cobalt levels
      in plasma were lowest in the Negative group and only this group showed a
      significant increase in vitamin B12 levels in blood after amalgam removal.

PMID- 17194928
TI  - Effect of selenium on thyroid hormone metabolism in filial cerebrum of mice with
      excessive iodine exposure.
AB  - The effects of supplementing selenium on thyroid hormone metabolism were studied
      on mice with excessive iodine exposure. The serum concentrations of thyroxine
      (T4) and triiodothyronine (T3) and the activities of iodothyronine 5?' and 5
      deiodinase (D2, D3) were measured in the brain of filial mice to study the
      influence of selenium on thyroid hormone metabolism. Measurements were carried
      out on postnatal day 0, 14, and 28. It was found that selenium supplementation
      alleviated the adverse effects of excessive iodine on progeny. The serum TT4
      level as well as TT4 and TT3 concentrations and D3 activity in cerebrum of
      progeny decreased, whereas D2 activity increased in the cerebrum of progeny on
      postnatal day 0 and 14. Selenium supplementation exerted some favorable effects
      on thyroid hormone metabolism in cerebrum of progeny of dam with excessive iodine
      intake.

PMID- 17194929
TI  - Silicon intake to vertebral columns of mice after dietary supply.
AB  - Vertebral columns were dissected and analyzed after birth with oral
      administration of silicon for 4 wk and for 8 wk. The silicon level was lower (20
      microg/g) at the beginning. It remains unchanged after 4 wk and then increases
      twice as much as that for those mice bred for 8 wk than those bred for 4 wk. This
      increase depends remarkably on the mass ratio of Si/Ca (M/M). The ratio increases
      to three times higher than that of the control at the beginning of the
      experiments (5 wk after birth). Although the S and P contents appeared to be
      lower, these increased when Si was administered in combination with
      phosphopeptide. Other elements, such as Ca, Mg, Fe, and Zn, appeared to be
      unchanged as the weeks proceeded. These findings seem to support a proposal that
      silicon is necessary for the growth of backbones in mice.

PMID- 17194930
TI  - Nonsense mediated decay induced by tethered human UPF3B is restricted to the
      cytoplasm.
AB  - The subcellular localization of the nonsense mediated decay (NMD) of mRNA
      transcripts bearing premature termination codons has been controversial.
      Recently, it has been demonstrated that RNA tethering of key mediators of NMD,
      including human UPF3B, accurately recreates NMD. Here, we have used tethered
      UPF3B, combined with regulation of nuclear mRNA export using the retroviral
      Rev/RRE system, to examine where UPF3B-mediated mRNA degradation occurs. Our data
      clearly demonstrate that nuclear mRNA export is required for UPF3B-mediated
      degradation and moreover show that this degradation is exclusively cytoplasmic,
      despite the fact that the UPF3B fusion protein used is a nucleocytoplasmic
      shuttle protein localized predominantly to the nucleus. Moreover, exclusively
      cytoplasmic NMD occurred whether the target mRNA was exported via the retroviral
      Rev/RRE pathway or via the Tap: Nxt pathway used by most cellular mRNAs. These
      data may suggest that truly nuclear NMD, if it occurs, is at least in part
      mechanistically distinct from cytoplasmic NMD.

PMID- 17194931
TI  - Molecular mimicry in translational regulation: the case of ribosomal protein S15.
AB  - Ribosomal protein S15 is highly conserved among prokaryotes. It plays a pivotal
      role in the assembly of the central domain of the small ribosomal subunit and
      regulates its own expression by a feedback mechanism at the translational level.
      The protein recognizes two RNA targets (rRNA and mRNA) that share only partial
      similarity. Its interaction with 16S rRNA has been fully characterized, while
      mRNA interactions and regulatory mechanisms have been extensively studied in E.
      coli and in T. thermophilus. Recently, we have characterized which aminoacids are
      involved in E. coli mRNA recognition, using an in vivo assay allowing to identify
      S15 mutations affecting the S15-mRNA interactions without altering 30S subunit
      assembly. Here, we address the following questions: Are common determinants used
      by S15 to recognize its rRNA and mRNA targets? What is the extent of molecular
      mimicry? Is the regulatory mechanism conserved? Our results indicate that
      specific recognition of mRNA and rRNA relies on both mimicry and site
      differentiation. They also highlight the high plasticity of RNA to adapt to
      evolutionary constraints.

PMID- 17194932
TI  - A surfeit of factors: why is ribosome assembly so much more complicated in
      eukaryotes than bacteria?
AB  - Recent years have seen a dramatic increase in the number of ribosome synthesis
      factors identified in the yeast Saccharomyces cerevisiae. Most of these are not
      predicted to directly catalyze either RNA processing or modification, and they
      are therefore predicted to function in some sense as assembly factors, promoting
      the assembly and/or disassembly of the processing and modification machinery,
      binding of the ribosomal proteins and correct folding of the pre-rRNAs and rRNAs.
      In contrast, ribosome synthesis in E. coli, which has also been extensively
      analyzed, appears to involve a very small number of potential assembly factors.
      Here we will consider the differences between eukaryotic and bacterial ribosome
      synthesis that may underlie this distinction.

PMID- 17194933
TI  - Aminoacyl-tRNA synthesis by pre-translational amino acid modification.
AB  - Aminoacyl-tRNAs (aa-tRNAs) are essential substrates for ribosomal translation,
      and are generally synthesized by aminoacyl-tRNA synthetases (aaRSs). It was
      expected earlier that every organism would contain a complete set of twenty
      aaRSs, one for each canonical amino acid. However, analysis of the many known
      genome sequences and biochemical studies revealed that most organisms lack
      asparaginyl- and glutaminyl-tRNA synthetases, and thus are unable to attach
      asparagine and glutamine directly onto their corresponding tRNA. Instead, a
      pretranslational amino acid modification is required to convert Asp-tRNA(Asn) and
      Glu-tRNA(Gln) to the correctly charged Asn-tRNA(Asn) and Gln-tRNA(Gln),
      respectively. This transamidation pathway of amide aa-tRNA synthesis is common in
      most bacteria and archaea. Unexpected results from biochemical, genetic and
      genomic studies showed that a large variety of different bacteria rely on tRNA
      dependent transamidation for the formation of the amino acid asparagine.
      Pretranslational modifications are not restricted to asparagine and glutamine but
      are also found in the biosynthesis of some other aa-tRNAs, such as the initiator
      tRNA fmet-tRNA(Met)(i) and Sec-tRNA(Sec) specifying selenocysteine, the 21(st)
      cotranslationally inserted amino acid. tRNA-dependent amino acid modification is
      also involved in the generation of aminolevulinic acid, the first precursor for
      porphyrin biosynthesis in many organisms.

PMID- 17194934
TI  - Antisense molecular beacon strategy for in situ visualization of snRNA and
      fibrillarin protein interaction in Giardia lamblia.
AB  - Use of confocal microscopy has provided many recent developments in the study of
      functional aspects, especially localization and distribution of proteins, DNA and
      RNA within the cells. In the present investigation, we have applied for the first
      time, antisense molecular beacon based Fluorescence Resonance Energy Transfer
      (FRET) and Flow Cytometric Energy Transfer (FCET) techniques to demonstrate
      binding and co-localization of fibrillarin protein with small nuclear RNA (snRNA)
      to form ribonucleoprotein particle (RNPP) complex in Giardia lamblia. It has been
      observed by FRET and FCET that energy transfer occurs from fluorescence tagged
      fibrillarin to snRNA antisense molecular beacon confirming the clear physical
      interaction between them during RNPP complex formation. This is the first
      demonstration of in situ detection of RNA-protein complex formation by antisense
      molecular beacon based FRET and FCET in Giardia lamblia.

PMID- 17194936
TI  - Downregulation enhanced green fluorescence protein gene expression by RNA
      interference in mammalian cells.
AB  - RNA interference (RNAi) is a recently observed process by which double-stranded
      RNA (dsRNA) directs sequence-specific degradation of messenger RNA (mRNA) in
      animal and plant cells. In several model systems, RNAi had been developed into a
      useful tool for the investigation of gene function. In order to study the
      effectiveness of RNAi in mammalian cells, we introduced chemically synthetic 21
      nucleotide small interference RNA (siRNA) duplexes into 293T/GFP cells, which
      were transduced by enhanced green fluorescence protein (EGFP) gene, by means of
      TransIT-TKO, Oligofectamine reagent, Lipofectamine 2000 respectively. The results
      demonstrated that EGFP expression was significantly and specifically inhibited by
      the corresponding dsRNA, but not by unrelated dsRNA. In three different vectors,
      Lipofectamine 2000 demonstrated the highest transfection efficiency with a 48 h
      exposure. The decrease in EGFP fluorescence intensity was approximately 80%.
      Although TransIT-TKO and Oligofectamine displayed similar trends, the
      transfections were inefficient, and often toxic. The results also exhibited that
      siRNA inhibited the EGFP gene expression in a dose and time-dependent manner.
      Therefore, we concluded that the Lipofectamine 2000 was a better transfection
      reagent for RNAi. RNAi pathway seems operative in mammalian embryo cells. RNAi
      may be developed into a potential tool for gene therapy.

PMID- 17194935
TI  - Evidence for U-tail stabilization of gRNA/mRNA interactions in kinetoplastid RNA
      editing.
AB  - The most dramatic example of RNA editing is found in the mitochondria of
      trypanosomes. In these organisms, U-insertions/deletions can create mRNAs that
      are twice as large as the gene that encodes them. Guide RNAs (gRNAs) that are
      complementary to short stretches of the mature message direct the precise
      placements of the U residues. The binding of gRNA to mRNA is a fundamental step
      in RNA editing and understanding the relative importance of the elements that
      confer affinity and specificity on this interaction is critical to our
      understanding of the editing process. In this study, we have analyzed the
      relative binding affinities of two different gRNA/mRNA pairs. The affinity of gA6
      14 for its message (ATPase 6) is high, with an apparent K(D) in the 5-10 nM
      range. In contrast, gCYb-558 has a low affinity for its cognate mRNA. Deletion of
      the gRNA U-tail caused a significant reduction in the binding affinity for only
      the gCYb-558 pair, and was observed only under physiological magnesium
      conditions. These results indicate that the U-tail contribution can differ
      substantially between the different gRNA/mRNA pairs. In addition, our results
      suggest that the efficiency of gRNA/mRNA interaction is highly dependent on
      thermodynamic parameters determined by the local sequences and their adopted
      structures surrounding the anchor-binding site.

PMID- 17194938
TI  - The ribosome as an RNA-based molecular machine.
AB  - The ribosome is a protein-synthesizing ribonucleoprotein particle where RNA forms
      its structural and functional core. Compact self-folding of ribosomal RNA
      resulting in its specific tertiary structure and its conformational mobility
      underlie the functional behavior of the ribosome. In addition to the functions of
      ligand recognition (binding of mRNA, tRNA and translation factors) and catalysis
      (peptidyltransferase activity), the ribosomal RNA with its movable blocks
      principally contributes to the construction of the ribosome as a molecular
      machine. The oscillations between open (unlocked) and closed (locked)
      conformations are proposed to be necessary events in the processes of aminoacyl
      tRNA binding, transpeptidation and translocation. Elongation factors EF-Tu and EF
      G with GTP are considered as catalysts of conformational transitions during
      aminoacyl-tRNA binding and translocation, and the theory of NTP-dependent
      conformational catalysis via conformational intermediates is discussed. Thermal
      fluctuations are assumed to serve as the main "motive force" to move RNA parts
      and ligands in the translating ribosome. The binding of functional ligands, such
      as aminoacyl-tRNA and an elongation factor with GTP, and the chemical reactions
      of transpeptidation and GTP hydrolysis play the role of a Maxwell's Demon: they
      rectify the random fluctuations to produce the unidirectional conveyance process
      and translation ("thermal ratchet" model).

PMID- 17194937
TI  - Ribosomal protein L3: influence on ribosome structure and function.
AB  - Early studies demonstrated roles for ribosomal protein L3 in peptidyltransferase
      center formation and the ability of cells to propagate viruses. More recent
      studies have linked these two processes via the effects of mutants and drugs on
      programmed -1 ribosomal frameshifting. Here, we show that mutant forms of L3
      result in ribosomes having increased affinities for both aminoacyl- and peptidyl
      tRNAs. These defects potentiate the effects of sparsomycin, which promotes
      increased aminoalcyl-tRNA binding at the P-site, while antagonizing the effects
      anisomycin, a drug that promotes decreased peptidyl-tRNA binding at the A-site.
      The changes in ribosome affinities for tRNAs also correlate with decreased
      peptidyltransferase activities of mutant ribosomes, and with decreased rates of
      cell growth and protein synthesis. In vivo dimethylsulfate (DMS) protection
      studies reveal that small changes in L3 primary sequence also have significant
      effects on rRNA structure as far away as 100 A, supporting an allosteric model of
      ribosome function.

PMID- 17194939
TI  - The RNA interference proteins and vasa locus are involved in the silencing of
      retrotransposons in the female germline of Drosophila melanogaster.
AB  - RNA interference (RNAi) is considered as a defense against expansion of
      transposable elements. The proteins related to RNA helicase and Argonaute
      families are involved in RNAi process in different organisms. It was shown that
      Argonaute AUBERGINE and putative RNA helicase SPINDLE-E proteins were essential
      for RNAi in Drosophila. Here, we describe the role of aubergine (aub) and spindle
      E (spn-E) genes in the control of LTR retrotransposon copia and nonLTR telomeric
      Het-A and I retrotransposons in ovaries. spn-E mutation causes a drastically
      increased lacZ expression driven by copia LTR. For the first time we show the
      involvement of AUBERGINE protein and VASA RNA helicase, essential for oocyte
      patterning, in the retrotransposon silencing. spn-E, vasa and aub mutations cause
      similar accumulation of both I element and Het-A transcripts in the developing
      oocyte. VASA and AUBERGINE proteins are known as components of perinuclear
      ribonucleoprotein particles in germ cells, and spn-E mutation disturbs protein
      content of the particles. We suggest participation of these proteins in the same
      silencing pathway.

PMID- 17194940
TI  - Synthesis of cysteinyl-tRNACys by a prolyl-tRNA synthetase.
AB  - The question of how cysteinyl-tRNA(Cys) is synthesized in organisms that lack a
      canonical cysteinyl-tRNA synthetase (CysRS) is an important open question in
      understanding protein synthesis. The prolyl-tRNA synthetase (ProRS) of wide
      ranging organisms has the ability to mis-activate cysteine without editing. This
      raises the question of whether the mis-activated cysteine can be charged to
      tRNA(Cys) to synthesize the correctly matched cys-tRNA(Cys), which may serve as
      an option in organisms that lack the conventional CysRS. Despite intense
      searches, such an activity has not been found. Here we show that the ProRS of the
      radiation-resistant bacterium Deinococcus radiodurans has the ability to charge
      cysteine to tRNA(Cys) and to retain the cognate pair cys-tRNA(Cys) stably without
      editing. The cysteinylation by D. radiodurans ProRS is not the major route for
      synthesis of cys-tRNA(Cys), however, because the organism encodes the
      conventional CysRS. Nonetheless, the synthesis of cys-tRNA(Cys) in vitro is
      important and it is unlike previously documented mis-charging of
      Methanocaldococcus jannaschii ProRS, which synthesizes cys-tRNA(Pro) but not cys
      tRNA(Cys). We suggest that the cysteinylation activity of D. radiodruans ProRS
      may, in the presence of additional factors, offer one option to organisms that
      lack the conventional CysRS to synthesize cysteinyl-tRNA(Cys) in vivo.

PMID- 17194941
TI  - 2006 International Society for the Study of Vulvovaginal Disease classification
      of vulvar dermatoses: a synopsis.

PMID- 17194943
TI  - Human papillomavirus detection in urine samples: an alternative screening method.
AB  - OBJECTIVES: To investigate the usefulness of human papillomavirus detection in
      the urine of women with poor gynecologic attention. MATERIALS AND METHODS: Fifty
      urine and 50 cervical samples from 50 women were analyzed. Polymerase chain
      reaction was performed on these 100 samples using consensus primers and a low
      density microarray-based method for human papillomavirus typing. RESULTS: The
      concordance of the results between both sample groups was 80%. In the urine
      samples, the sensitivity of polymerase chain reaction for high-grade squamous
      intraepithelial lesion was 100%, the specificity was 80%, the positive predictive
      value was 91%, and the negative predictive value was 100%. CONCLUSIONS: Human
      papillomavirus detection in urine samples may be used as an alternative screening
      method for women with poor gynecologic attention.

PMID- 17194944
TI  - Cytological evaluation correlates poorly with histological diagnosis of vulvar
      neoplasias.
AB  - OBJECTIVE: To determine whether cytological smears of the vulva correlate with
      vulvar biopsies of vulvar intraepithelial neoplasias (VINs). MATERIALS AND
      METHODS: A retrospective chart review (1995-2000) was performed to identify cases
      of VIN and vulvar carcinoma and to correlate vulvar Pap smears with biopsy
      results. RESULTS: Four hundred vulvar Pap smears were identified. Fifty of these
      patients had concomitant vulvar biopsies, and these cases constitute our study
      group. Twenty-two of these 50 women had biopsy-proven VIN or vulvar carcinoma.
      Only 7 (32%) of 22 patients with biopsy-proven disease had a vulvar Pap smear
      significant for VIN or vulvar carcinoma. The kappa statistic was 0.30 (95%
      CI=0.08-0.52), indicating poor agreement between vulvar cytology and biopsy
      results. CONCLUSIONS: Vulvar cytological evaluation did not correlate well with
      tissue diagnosis of VIN; and thus, our findings do not support the use of vulvar
      cytology in the clinical management of VIN.

PMID- 17194945
TI  - Autoclave sterilization of instruments used on women with cervical neoplasia is
      an effective method of eradicating residual human papillomavirus DNA: a
      polymerase chain reaction-based evaluation.
AB  - OBJECTIVE: To determine whether autoclave sterilization eradicates human
      papillomavirus (HPV) DNA on specula and instruments used to treat women with
      cervical neoplasia. METHODS: Specula and instruments used in two referral
      colposcopy clinics were evaluated to determine the PGMY9/11 primer system's
      ability to amplify residual HPV DNA. Each speculum and instrument was sampled
      with a Dacron swab and stored in PreservCyt solution (Cytyc Corporation,
      Marlborough, MA) at 4 degrees C. DNA amplification was performed under standard
      conditions with appropriate controls followed by HPV typing using the reverse
      line blot test (Roche Molecular Systems, Alameda, CA). Once validated, the same
      polymerase chain reaction method was used on autoclave-sterilized specula and
      biopsy instruments and heated glass bead- and Cidex bath (Johnson & Johnson, New
      Brunswick, NJ)-sterilized instruments. All results, with appropriate positive and
      negative controls, were confirmed in triplicate. RESULTS: A total of 140
      instruments (70 used and 70 autoclaved) were sampled for residual HPV DNA. Five
      samples in the contaminated specula arm were excluded from analysis secondary to
      insufficient sampling. Of the remaining samples, 52.3% (34/65) of contaminated
      instruments-both specula and biopsy instruments-had detectable HPV DNA. Fifty
      five percent of contaminated biopsy instruments (11/20) were positive and 51.1%
      of contaminated specula (23/45) were positive. All 70 autoclaved samples (50
      specula and 20 biopsy instruments) were negative for residual HPV DNA or beta
      globin. One instrument in the glass bead and Cidex group that was presumed
      sterile was positive for HPV 16 DNA. CONCLUSIONS: The PGMY9/11 primer system is
      an effective method to detect residual HPV DNA. Autoclave sterilization appears
      to eradicate HPV DNA to levels undetectable with this sensitive assay, whereas
      heated glass beads followed by Cidex bath appears to be inadequate methods. These
      results suggest that autoclave sterilization is effective when using
      nondisposable instruments and should be the method of choice in studies using
      polymerase chain reaction-based amplification of HPV DNA.

PMID- 17194947
TI  - Gene expression profiling of women with varying degrees of cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: A pilot study to determine genomic microarray differences in patients
      with normal cervical tissue and cervical intraepithelial neoplasia (CIN) 3.
      MATERIALS AND METHODS: After institutional review board approval, patients
      referred to the University of Alabama at Birmingham Colposcopy Clinic for a loop
      electrosurgical excisional procedure were identified. Tissue biopsies of both
      normal tissue and CIN 3 from fresh loop electrosurgical excisional procedure
      specimens were obtained and sent to pathology for histological confirmation.
      Procurement of these 2 types of tissue from the same patient controls for
      different types of human papillomavirus infection, smoking and nutritional
      status, age, immunocompetency, and other microenvironment factors (i.e., the
      patient serves as their own control). Standard RNA extraction techniques (Qiagen,
      Inc., Valencia, CA) were used to prepare the tissue specimens for microarray
      analysis with the Affymetrix GeneChip U133A expression array (Affymetrix, Inc.,
      Santa Clara, CA). Paired samples were eligible for microarray analysis only when
      both normal tissue and CIN 3 were confirmed by pathology. The data were then
      subsequently subjected to a log-like transformation and analyzed with a t test.
      For this study, p<.001 was determined to be statistically significant. RESULTS:
      Twenty-one pairs of both normal and CIN tissues were obtained and underwent
      histological evaluation followed by RNA extraction. Within the normal group, 86%
      were confirmed as true normals and 14% as CIN. Within the CIN group, 28.5% were
      found to have CIN 2, 62% were found to have CIN 3, and 9.5% had no evidence of
      CIN. Mean RNA content of normal samples was 2.0 microg, whereas the mean RNA
      content of CIN samples was significantly higher at 7.4 microg (p=006).
      Ultimately, 5 pairs of normal and neoplastic tissues were subjected to microarray
      analysis. Using a cutoff of p<.001, 24 candidate genes were identified from more
      than 18,000 genes. In the CIN 3 group, 14 genes were overexpressed and 10 genes
      were underexpressed. Of the 14 overexpressed genes, 9 were noted to have
      identities listed in the National Center for Biotechnology Information public
      domain. Five (56%) of these 9 genes were directly related to immunity-related
      pathways, and 3 (33%) of the 9 genes were found to be involved in cell cycle
      function/control. One overexpressed gene was identified as p53. CONCLUSIONS: The
      presence of CIN is marked by increased transcriptional activity, evident by an
      almost 4-fold increase in mean RNA content obtained from our CIN samples versus
      normal cervical tissue. Furthermore, a number of statistically significant
      overexpressed genes of interest related to immune function/response and cell
      cycle control were identified in our pilot microarray study. This data have the
      ability to direct future research endeavors in cervical neoplasia. Future
      endeavors include the use of laser capture microdissection to evaluate genomic
      changes strictly at the epithelial level and, as such, exclude stromal response
      contributions.

PMID- 17194946
TI  - Spectroscopic imaging as a triage test for cervical disease: a prospective
      multicenter clinical trial.
AB  - OBJECTIVE: The objective of the study was to evaluate the potential safety and
      effectiveness of tissue spectroscopy for the diagnosis of cervical cancer in a
      prospective multicenter study of women scheduled for colposcopy on the basis of
      an abnormal Pap test or other risk factor. MATERIALS AND METHODS: Five hundred
      seventy-two women underwent spectroscopy of the cervix during their colposcopy
      visit. Spectroscopy measurements taken over a scan period of 4 minutes and 30
      seconds were integrated by a cross-validated pattern recognition model and
      compared with biopsy results to yield sensitivity and specificity of cervical
      spectroscopy. RESULTS: The median age of subjects enrolled in the study was 27.7
      years. The sensitivity of cervical spectroscopy was 95.1% with a corresponding
      55.2% specificity for benign lesions. Several potential confounding factors (eg,
      mucous, blood, patient motion, ambient light) were examined to determine their
      potential impact on the accuracy of the test. Ambient light seemed to have the
      greatest effect, but no single factor contributed significantly to the results.
      The subjects did not experience any adverse events from undergoing the test.
      CONCLUSIONS: Spectroscopy of the cervix has the potential to accurately detect
      cervical moderate and high-grade dysplasia while also reducing the false-positive
      rate for benign cervices. The test is relatively simple to implement and was well
      accepted by subjects enrolled in the study.

PMID- 17194948
TI  - Patient knowledge about human papillomavirus and relationship to history of
      abnormal Papanicolaou test results.
AB  - OBJECTIVE: To assess patient knowledge about human papillomavirus (HPV) and
      determine if self-report of a previous abnormal Papanicolaou test result improves
      knowledge. MATERIALS AND METHODS: A survey was designed and administered to
      patients at three obstetrics and gynecology clinics in Milwaukee, WI. The
      anonymous surveys assessed demographics, history of sexually transmitted
      infections or abnormal Papanicolaou test results, and knowledge about HPV and
      cervical cancer. The chi and Wilcoxon tests were used for statistical
      comparisons. RESULTS: Three hundred sixty-three surveys were collected,
      representing a diverse patient population. Forty-two percent of patients had
      heard of HPV. Women who reported a history of abnormal Papanicolaou test results
      were not more likely to have heard of HPV or to know that it causes cervical
      cancer than those who did not report abnormal Papanicolaou test results.
      CONCLUSIONS: There is no significant difference in knowledge about HPV between
      patients who reported a history of abnormal Papanicolaou tests and those who did
      not.

PMID- 17194949
TI  - Preclinic appointment telephone contact: an effective intervention for colposcopy
      clinic nonattendance.
AB  - OBJECTIVE: To assess the impact of preclinic appointment telephone contact with
      prospective patients on colposcopic clinic default rates. MATERIALS AND METHODS:
      All women attending the Cornwall Colposcopy Service in Truro, UK, between July
      and October 2003, were recruited and randomly assigned into two groups. The
      patients in one group (group A) were contacted by telephone 12 to 24 hours before
      their clinic appointments to be reminded of their appointments. Confirmation of
      their attendance was obtained. For patients who indicated their inability to
      attend, a new date and time was offered. The patients in the other group (group
      B) were not contacted by telephone. RESULTS: Ninety-one percent of patients
      randomized to group A attended their clinic appointment compared with 69% of
      patients in group B (who had no preclinic appointment telephone contact)
      (chi1=15.74; p=00073). The odds ratio was 4.68 (95% CI=2.8-10.45), thus implying
      that patients who were contacted by telephone before their clinic appointment are
      about five times more likely to attend compared with their counterparts who were
      not contacted by telephone. CONCLUSIONS: Our study shows that preclinic
      appointment telephone contact of prospective patients attending colposcopy clinic
      was an effective intervention to reduce clinic nonattendance.

PMID- 17194950
TI  - Music or guided imagery for women undergoing colposcopy: a randomized controlled
      study of effects on anxiety, perceived pain, and patient satisfaction.
AB  - OBJECTIVE: It was hypothesized that music or guided imagery versus usual care
      would result in less anxiety and perceived pain for colposcopy patients.
      MATERIALS AND METHODS: Patients were randomized to music, guided imagery, or
      usual care after completing a baseline questionnaire. All patients completed a
      postprocedure questionnaire. RESULTS: Study participants (N=170) had a mean age
      of 28.4 years (SD=9.6; range 18-60) and formed a racially diverse group.
      Education/income levels were low. No between-group differences were found for
      postprocedure anxiety or pain rating. CONCLUSIONS: Mind-body interventions had no
      statistically significant impact on reported anxiety, perceived pain, or
      satisfaction with care, even for those who anticipated the most pain or started
      with high anxiety.

PMID- 17194951
TI  - Report of a new ISSVD classification of VIN.

PMID- 17194952
TI  - Report of the International Society for the Study of Vulvovaginal Disease
      terminology and classification of vulvodynia.

PMID- 17194953
TI  - Vaginal solitary fibrous tumor: a case report with recurrence after incomplete
      excision.
AB  - OBJECTIVE: Primary solitary fibrous tumors (SFTs) of the female genital tract are
      exceedingly rare. We report a spindle cell tumor of the vagina with features
      consistent with a SFT in a 52-year-old woman. MATERIALS AND METHODS: The original
      tumor was studied with the appropriate panel of immunohistochemical stains. The
      first recurrence of the tumor was 10 months after its original incomplete
      excision, and a second recurrence occurred 29 months later. Both recurrences were
      analyzed using the same immunohistochemical panel. RESULTS: After considering
      several related differential diagnoses, the diagnosis of SFT was made based on
      the morphological and immunophenotypic features. CONCLUSION: To the best of our
      knowledge, this is the third case of vaginal SFT in the English literature, with
      2 recurrences after incomplete excision.

PMID- 17194954
TI  - Home Study Course: winter 2007.

PMID- 17194956
TI  - Increased expression of chitinase 3-like protein 1 secondary to joint immobility.
AB  - Previous studies have established mechanical stimulation of joints is necessary
      to maintain the structure and function of the articular cartilage. Immobilization
      of the rat knee joint induces cartilage degeneration and reduces the joint range
      of motion, two of the clinical parameters used to define a joint contracture. We
      hypothesized chondrocytes from articular cartilage increase their expression of
      the chitinase 3-like protein 1 (CHI3L1) gene in response to joint immobility. We
      selected the CHI3L1 gene on the basis of its identification as a differentially
      expressed gene in the articular cartilage obtained from immobilized rat knee
      joints. Expression of CHI3L1 mRNA was increased after 2 and 4 weeks of
      immobility. A time-course study revealed that CHI3L1 immuno-reactivity was
      increased at 2 and 4 weeks and return to basal levels at all later time points.
      CHI3L1 gene adds to the list of differentially expressed genes defining the
      response of cartilage to joint immobility. Our data confirm a protective role for
      CHI3L1 in the initial phase of degeneration induced by immobility.

PMID- 17194957
TI  - Lateral hip pain: does imaging predict response to localized injection?
AB  - Lateral hip pain is a common complaint in patients with a history of lower back
      pain from spinal disease. These patients often are diagnosed and treated for
      trochanteric bursitis because of localized pain and tenderness in the lateral
      hip. We presumed numerous scintigraphic features could provide diagnostic
      criteria for diagnosing gluteus medius tendinitis and trochanteric bursitis. A
      study was designed to assess the scintigraphic criteria for diagnosis of
      trochanteric bursitis and to evaluate the relationship of trochanteric bursitis
      to gluteus medius tendinitis and lumbar degenerative disease in predicting
      relapse after injection. We evaluated 97 patients with greater trochanteric pain
      syndrome to find a correlation between trochanteric bursitis, gluteus medius
      tendinitis, and spinal degenerative disease using scintigraphy and magnetic
      resonance imaging. We also evaluated predictors for responding to trochanteric
      injection of local anesthetic/glucocorticoid injection. We found a correlation
      between lumbar degenerative disease, gluteus medius tendinopathy, and
      trochanteric bursitis. Of these, 30 of 48 patients (63%) responded to injection
      of local anesthetic and glucocorticoids. The major predictor of relapse of pain
      after injection in 18 patients was the presence of moderate to severe lumbar
      degenerative disease seen on scintigraphic imaging. We propose a mechanistic
      model of the greater trochanteric pain syndrome to explain the interrelationship
      and response to therapy. Scintigraphy can provide sensitive and specific
      diagnoses of gluteus medius tendinitis and trochanteric bursitis.

PMID- 17194958
TI  - Partial scapulectomy for congenital elevation of the scapula.
AB  - We treated 26 patients with congenital elevation of the scapula by excising the
      superomedial part of the scapula. We also simultaneously resected the
      omovertebral bone when present. A modified inverted L-shape incision was used to
      release the contracted tissue around the medial edge of the scapula. We evaluated
      28 shoulders (26 patients) at a minimum of 10 months followup (mean, 3.9 years;
      range, 10 months-7 years). The improvement rate for range of shoulder abduction
      was 59.11%. Eighteen shoulders with preoperative abduction less than 120 degrees
      achieved an average improvement of 52 degrees, whereas 10 shoulders with a
      preoperative abduction range greater than 120 degrees achieved an average
      improvement of 19 degrees. However, there was no difference in the improvement
      rate of the range of shoulder abduction between the two groups (60.94% versus
      56%). Twenty-three shoulders (82.24%) attained various degrees of cosmetic
      improvement after the operation. There were no neurologic complications during or
      after surgery. No patients complained of scar problems. Excising the superomedial
      part of the scapula is a safe, simple operation for treating congenital elevation
      of the scapula.

PMID- 17194959
TI  - Looking for answers in all the wrong places.

PMID- 17194960
TI  - Should testosterone be added to estrogen-progestin therapy for breast protection?

PMID- 17194961
TI  - Botanical and dietary supplements for mood and anxiety in menopausal women.
AB  - OBJECTIVE: This paper reviews the commonly used botanicals for treatment of mood
      and anxiety disorders in perimenopausal and postmenopausal women and presents
      information on their safety and efficacy. DESIGN: The MEDLINE and EMBASE
      databases were searched for clinical trials related to the use of botanicals for
      depression, anxiety, and mood disturbances. Papers were excluded if they were in
      a language other than English, did not include midlife women as study
      participants, or did not report on changes in mood, depression, or anxiety.
      RESULTS: Five of seven trials of St. John's wort for mild to moderate depression
      showed a significant improvement. The one randomized, controlled trial of ginseng
      in postmenopausal women reported improvements in mood and anxiety. All three
      randomized, controlled trials of ginkgo found no effect on depression. In four of
      eight controlled trials, kava significantly reduced anxiety. Black cohosh
      significantly reduced depression and anxiety in all studies reviewed.
      CONCLUSIONS: St. John's wort and black cohosh appear to be the most useful in
      alleviating mood and anxiety changes during menopause. Ginseng may be effective,
      but more research needs to be done. Kava holds promise for decreasing anxiety in
      peri- and postmenopausal women; however, women should be careful in the amount
      and duration of use. Finally, ginkgo and valerian do not appear to be useful in
      reducing depression or anxiety in this population.

PMID- 17194962
TI  - Aged rats lose vasoprotective and anti-inflammatory actions of estrogen in
      injured arteries.
AB  - OBJECTIVE: 17beta-estradiol (E2) negatively modulates neointima formation,
      leukocyte infiltration, and proinflammatory mediator expression after vascular
      injury in young (10-wk-old) ovariectomized (OVX) rats. Trials of E2 in elderly
      postmenopausal women have not confirmed a vasoprotective effect. This study
      tested the hypothesis that responsiveness to E2 is lost in injured arteries of
      aged (12-mo-old) OVX rats. DESIGN: E2- or vehicle-treated OVX rats underwent
      balloon injury of the carotid artery and were killed after 2 weeks for
      morphometric examination of arteries, after 24 hours for assessment of leukocyte
      infiltration, and after 2 hours for quantification of proinflammatory mediator
      mRNA expression. RESULTS: Neointima formation was significantly reduced in aged
      compared with young vehicle-treated rats. E2 treatment had directionally opposite
      effects on intima/media ratios in aged (+75%) and young (-40%) rats. Injury
      induced increases in infiltrating total leukocytes, neutrophils,
      monocytes/macrophages, and expression of proinflammatory mediators in arteries of
      aged rats; E2 had no effect on these inflammatory responses to injury. Estrogen
      receptor alpha and beta protein expression were similar in carotid arteries of
      young and aged rats on immunofluorescence testing. CONCLUSIONS: Aged OVX rats
      lose the vasoprotective and anti-inflammatory responses to exogenous E2 seen in
      younger animals. These results may be relevant to the lack of vasoprotection
      observed in outcome trials of estrogen therapy in postmenopausal women.

PMID- 17194963
TI  - Hot flashes and estrogen therapy do not influence cognition in early menopausal
      women.
AB  - OBJECTIVE: To examine how menopausal symptoms and estrogen therapy (ET)-induced
      symptom relief affect cognition in early menopause. DESIGN: There were two
      components. Part 1 was a cross-sectional study of 37 healthy, recently
      postmenopausal women with diverse menopausal symptoms. Women were categorized as
      having low (n=20) or high symptoms (n=17) based on a validated symptom
      questionnaire. Women completed mood and sleep questionnaires and underwent
      cognitive testing, which included verbal memory, visual memory, emotional memory,
      and verbal fluency. Thirty-two of these women went on to part 2 of the study.
      Fourteen were randomly assigned to receive ET and 18 to receive placebo for 8
      weeks. Before treatment and at 4 and 8 weeks, women completed the same measures
      as in part 1 of the study. RESULTS: High symptom women had more negative mood
      (P=0.01) and lower quality sleep (P<0.001) than low symptom women. Despite
      suffering from more menopausal symptoms, worse mood, and poorer sleep, women in
      the high symptom group performed the same on cognitive testing as women in the
      low symptom group. Women receiving ET had greater improvements in menopausal
      symptoms and sleep compared with those receiving the placebo (P<or=0.05). ET did
      not improve mood compared with placebo. Women receiving ET did not have any
      improvement in cognitive performance compared with those receiving the placebo.
      CONCLUSIONS: Menopausal symptoms do not impair cognition. ET does not improve
      cognition despite alleviating symptoms and improving sleep in recently naturally
      menopausal women with diverse menopausal symptoms.

PMID- 17194965
TI  - [Premature ovarian failure].
AB  - Premature ovarian failure (POF) is defined by at least four months of amenorrhea
      with elevated gonadotropins (usually above 40 UI/L) detected on two occasions a
      few weeks apart, in a woman before the age of 40. It occurs in 1 out of 10,000 in
      women below the age of 20, 1/1,000 below 30 and 1% in women before the age of 40.
      In 80% of POF cases, the etiology is unknown, except for Turner syndrome. The
      different etiologies identified are 1) iatrogenic following chemotherapy and/or
      radiotherapy, 2) autoimmune, 3) viral, 4) genetic (RFSH, FOXL2, FRAXA, BMP15,
      GDF9, GALT, 17 hydroxylase...). Management of these patients includes hormone
      replacement therapy in order to avoid an increase in cardiovascular risk and
      osteoporosis related to hypoestrogenism. Infertility is common, as only 3 to 10%
      of the patients will have natural conception. When fertility is desired, women
      with POF should be oriented towards oocyte donation centers. Research is
      currently performed in order to identify new genes involved in POF.

PMID- 17194966
TI  - Anti-mullerian hormone: clinical relevance in assisted reproductive therapy.
AB  - Anti-Mullerian Hormone (AMH) is a member of the transforming Growth Factor-B (TGF
      B) family synthesized exclusively by the gonads of both sexes. Over the last four
      years, numerous studies have examined the clinical usefulness of serum AMH levels
      as a predictor of ovarian response and pregnancy in assisted reproductive
      technology cycles. Assessment of ovarian reserve in women undergoing assisted
      reproduction is useful in optimising the treatment protocol. Availability of a
      reliable measure of ovarian reserve is essential. Currently, serum AMH level
      seems to be more strongly related to the ovarian reserve and to be a more
      discriminatory marker of assisted reproductive technology outcome than follicle
      stimulating hormone, inhibin B or estradiol, which are more commonly used
      markers. Our study involving 69 women undergoing a cycle of in vitro
      fertilisation (IVF) or intracytoplamic sperm injection (ICSI) treatment,
      confirmed these results. We have shown in this study that AMH is significantly
      correlated with the number of eggs collected and is of great interest as a
      negative predictive value for the success of assisted reproductive technology
      (ART). Further studies are needed to determine AMH cut-off values.

PMID- 17194967
TI  - [Skin and menopause].
AB  - Important changes related to declining level of several hormones occur during
      menopause: vasomotor instability, bone loss, anxiety, sexual dysfunction, skin
      aging... Our objective was a review of the literature concerning the histological
      and clinical changes seen in post menopausal skin, and also an analysis of the
      effect of hormonal replacement therapy in slowing down the aging process. Decline
      in progesterone increases the impact of androgen on the sebaceous glands and
      hair. Decreased estrogen slows down mitotic activity in the epidermal basal
      layer, reduces the synthesis of collagen and contributes to thickening of the
      dermo-epidermal junction. This hypoestrogenemia may be spontaneously attenuated
      by local synthesis of oestradiol in peripheral target tissues according to the
      intracrine process. This new hormonal pattern is associated with skin atrophy,
      hyperseborrhea, increased pilosity on the cheeks and upper lip, loss of scalp
      hair, increase in degeneration of elastic tissue, atrophy and dryness of the
      vaginal mucosa. Estrogen treatment in post menopausal women has been shown to
      increase collagen content, dermal thickness and elasticity. Biophysical
      properties are also significantly improved for the parameters reflecting
      hydration and sebum secretion. However, numerous side effects such as increased
      incidence of cancer and cardiovascular morbidity limit the use of this treatment.
      So non hormonal alternatives are proposed. Laser and lifting remain the most
      important options.

PMID- 17194968
TI  - Contribution of genetic analysis in screening for MEN1 among patients with
      sporadic disease and one or more typical manifestation.
AB  - Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant hereditary
      syndrome (OMIM 131100) due to MEN1 gene mutations, predisposing to the
      development of hyperplasic and tumoral lesions of neuroendocrine tissues. Since
      the identification of the gene in 1997, more than 400 different mutations of MEN1
      have been registered. Genotypic analysis of MEN1 remains fastidious and must be
      reserved to targeted situations. If the lesions appear in a familial assessed
      context, there is a strong argument to search for MEN1 mutation. This is not the
      case in a sporadic context. With experience acquired in our laboratory, we
      evaluated the frequency of MEN1 mutations in patients with sporadic
      presentations. Our aim was to better define criteria for MEN1 genotypic analysis.
      One hundred and twenty four blood samples from unrelated patients, who gave their
      written informed consent, were analyzed. These patients exhibited 1 to 4
      manifestations of MEN1 without any familial context. After DNA extraction, the
      analysis was undertaken by PCR-sequencing of all the MEN1 coding exons and
      exon/intron boundaries or by PCR of the pre-screened fragments alone, a technique
      made possible by indirect screening mutation methods. Mutations were identified
      by comparing the sequences to the reference MEN1 sequence available from GENBANK
      (U93237.1). Mutations were identified in 19 patients, with variable prevalence
      according to clinical manifestations: 100% for patients with 4 manifestations,
      45.5% for patients with 3 manifestations, 19% for patients with 2 manifestations
      and 2% for patients with only one manifestation. Mutations were: 11 point
      variations (58%), including 2 splicing sites and 8 frameshift mutations (42%)
      including 5 deletions, 2 insertions and 1 insertion/deletion; one mutation was
      identified twice. We showed a relationship between clinical presentation and MEN1
      mutation identification, especially with the number of clinical manifestations
      but also with the type of manifestation. Pancreatic manifestations were
      significantly linked with probability of mutation. In a sporadic context with at
      least two established manifestations of MEN1, the overall probability of
      identifying a mutation was 26%, warranting MEN1 genotypic analysis.

PMID- 17194969
TI  - [Prevalence of diabetes-related autoantibodies in celiac disease].
AB  - THE AIM: of this study is to investigate the prevalence of diabetes-related
      autoantibodies in a group of children with celiac disease and to compare it with
      a control group. MATERIAL AND METHODS: We recruited 31 celiac children at
      diagnosis (on gluten containing diet) and 31 age and sex matched healthy
      children. Anti-islet cell antibodies (ICA) were detected by indirect
      immunofluorescence on monkey pancreas. Anti-glutamate decarboxylase (anti-GAD)
      and anti-tyrosine phosphatase (anti-IA2) antibodies were assessed by a radio
      immuno- precipitation method. RESULTS: Three out of 31 celiac patients (9.7%) had
      one or more diabetes-related autoantibodies. ICA, anti-GAD and anti-IA2 were
      found in respectively 3.2%; 3.2% and 9.7% of patients. Only one control (3.2%)
      had anti-GAD. There was no statistically significant difference between the 2
      groups. CONCLUSION: The risk to develop diabetes seems to be the same in celiac
      patients and in healthy subjects thus screening of diabetes-related
      autoantibodies is not justified in celiac patients.

PMID- 17194970
TI  - [Epidemiologic study of autoimmune thyroid disease in south Tunisia].
AB  - In order to study incidence and prevalence of autoimmune thyroid diseases
      (AITDs), we studied a retrospective cohort of 1,079 patients explored in the
      department of Endocrinology of Sfax (south of Tunisia). The overall incidence of
      AITDs was 9.9%. Mean age was 39.6+15 years; sex ratio 5 F/1M. Graves' disease was
      the most frequent (45%). Atrophic thyroiditis was present in 32.2% of patients
      and Hashimoto's thyroiditis in 22.8%. The incidence of AITDs increased from 1990
      to 2000 and by 2003 it had fallen to 67 cases per year. TPO antibody was present
      in two-thirds of patients with Hashimoto thyroiditis, and half of those with
      atrophic thyroiditis. TG antibodies were less frequent (one-third of patients).
      Association with other autoimmune diseases was noted in 6.3% of patients: type I
      diabetes mellitus, adrenal insufficiency and vitiligo. Statistic analysis did not
      disclose any association between autoantibody levels and thyroid dysfunction.
      There was an association between TG antibody and TSH levels among patients with
      Graves' disease and between TG antibody level and age in atrophic thyroiditis
      patients (p<0.05); a correlation was also noted between these antibodies and
      other autoimmune diseases (p=0.05). It is difficult to assess the frequency of
      ATD in the clinical setting. Characteristic features of AITDs in patients seen in
      south Tunisia were found to be similar to those described in the literature.
      Other more large-scale representative studies would be useful to establish the
      epidemiology of AITDs in Tunisia.

PMID- 17194971
TI  - HLA class II distribution in Congolese with hyperthyroidism: preliminary results.
AB  - OBJECTIVE: Incidence of the hyperthyroidism is continuously increasing, whereas
      our knowledge concerning the facilitating or etiologic factors of this increase
      are still partial. To evaluate some of these unknown factors, we started this
      preliminary study, in order to identify HLA genes in hyperthyroid Congolese, and
      to determine their susceptibilty in the appearance and development of
      hyperthyroidism at the Hospital Clinic of Kinshasa. MATERIALS AND METHODS: Nine
      Congolese women with hyperthyroidism, and thirteen healthy controls (3 women and
      10 men) were examined and compared for HLA-DR and HLA-DQ genes analyses, from
      August 2000 to August 2002. DRB1 and DQB1 alleles were identified, using the
      Polymerase Chain Reaction (PCR) and immobilized sequence-specific oligonucleotide
      (SSO HLA-DRB1 and DQB1 test) probes assays. RESULTS: In the group with
      hyperthyroidism, three alleles (HLA-DR1, HLA-DR2, HLA-DR3) and an allele group
      (HLA-DR11,13,14) were found for DRB1 locus, while only one allele (HLA-DQB1*0602)
      was identified for DQB1 locus; allele group HLA-DR11,13,14 was the most frequent
      (allele frequency=0.50), followed by HLA-DR3 allele (allele frequency=0.222); 6
      haplotypes were observed, with predominance of haplotype DR3/DR11,13,14 (genotype
      frequency=0.333), followed by haplotype DR11,13,14/DR11,13,14-DQB1*0602 (genotype
      frequency=0.222). In the group of healthy controls, three alleles (HLA-DR2, HLA
      DR3, HLA-DR4) and an allele group (HLA-DR11,13,14) were identified for DRB1; HLA
      DR2 allele was predominant (allele frequency=0.615), followed by allele group HLA
      DR11,13,14 (allele frequency=0.231); a statistic significant difference was
      observed between the frequencies of DR2 allele and allele group DR11,13,14 in the
      healthy controls compared to those of hyperthyroid patients (p=0.02); 6
      haplotypes were also detected in this group, the most frequent haplotype being
      HLA-DR2/DR2-DQB1*0602 (genotype frequency=0.540 versus 0.333 in the hyperthyroid
      group) (p=0.048). HLA-DQB1*0602 was dominant in the healthy controls group
      (allele frequency=0.890), versus HLA-DQB1*0302 (allele frequency=0.110).
      CONCLUSIONS: HLA-DR2, HLA-DQB1*0602 and DR2/DR2-DQB1*0.602 would play a
      protective role against the hyperthyroidism, while DR3 allele, allele group
      DR11,13,14 and haplotype HLA-DR3/DR11,13,14 would predispose to this disease or
      to Graves' exophtalmopathy. A large and profound study is needed to confirm our
      preliminary results.

PMID- 17194972
TI  - [MRI pituitary stalk abnormalities: etiology aspects in 11 patients].
AB  - Newer techniques of magnetic resonance imaging (MRI) describe more accurately
      pituitary stalk abnormalities such as infections, infiltrative lesions and
      tumors. In absence of all the above mentioned etiological factors, genetics
      defects are suspected, mainly when other malformations are equally present. We
      attempt to show through 11 observations the variability of pathologies involving
      the pituitary stalk with their respective clinical and radiological features and
      associated endocrine abnormalities. This is a retrospective study of 7 men (67%)
      and 4 women (33%), mean age of 28 year (range: 15 to 53) in whom pituitary MRI
      was performed for hypopituitarism, diabetes insipidus or hyperprolactinemia.
      Three patients had brain MRI for an extra-pituitary condition. The pituitary MRI
      showed a stalk section in 3 cases (27%), atrophy in 1 case and thickening in 7
      cases (67%). The pituitary stalk anomaly was associated with hyperprolactinemia
      in 3 cases (27%), central diabetes insipidus in 4 cases (36%), growth hormone
      deficiency in 4 cases (36%), adrenal insufficiency in 5 cases (45%), hypogonadism
      in 5 cases (45%) and hypothyroidism in one case (9%). Established diagnoses were:
      sellar metastasis in 2 cases (18%), Langerhans' histocytosis, tuberculosis and
      autoimmune hypophysitis respectively in 3 cases (9%). In 6 cases (54%), no clear
      etiology was found. Given the multitude of pituitary stalk pathologies, a
      detailed etiologic inquiry must be performed in order to detect elements able to
      reclassify an initially idiopathic disorder.

PMID- 17194973
TI  - [Contribution of ultrasonography to the diagnosis of non-hormonal acquired
      clitoromegalia: a case report].
AB  - We report the case of a 30-year-old woman, consulting for a painful clitoromegaly
      which developed progressively and rapidly. The gyneco-endocrinological assessment
      ruled out hyperandrogenism. Ultrasound examination of the clitoris revealed the
      presence of a clitoral cyst. Acquired clitoromegaly is a symptom which occurs in
      severe hyperandrogenism. Other organic etiologies include clitoral cysts of
      various nature and solid tumors. An ultrasonographic examination should be
      included in the diagnostic work-up for acquired clitoromegaly.

PMID- 17194974
TI  - [Hypoparathyroidism associated with systemic lupus erythematosus: a case].
AB  - Hypoparathyroidism is very rarely diagnosed in patients with lupus. CASE: A 39
      year-old women had systemic lupus erythematosus known for 3 years. She was
      admitted for a paresthesia of the lower limb, depression, insomnia and 5 kg
      weight loss. The laboratory tests revealed hypoparathyroidism and no sign of
      disease activity. Treatment with oral calcium and vitamin D resulted in
      correction of the hypocalcemia and QT prolongation. DISCUSSION: The combined
      diagnosis lupus-hypoparathyroidism has very rarely been reported. We suggest
      there may be a common underlying pathological process linking the two diseases.
      The occurrence of these diseases in the same individual may be related to an
      underlying genetic predisposition or secondary to the generalized autoimmune
      disease process.

PMID- 17194975
TI  - [Langerhans cell histiocytosis of the thyroid].
AB  - Langerhans histiocytosis is a disease with a very diverse clinical spectrum and a
      very varied prognosis. The thyroid localization is relatively rare, and raises
      diagnostic and therapeutic difficulties. Diagnosis often requires recourse to
      clinical, radiological and pathological confrontation. Combined medical and
      surgical treatment is indicated and requires close multidisciplinary cooperation.
      On the basis of a new observation and data in the literature, we present a
      progress report on the clinical and therapeutic options preferred by various
      authors.

PMID- 17194976
TI  - [Adrenal gland hemangioma: a case report].
AB  - Hemangioma is a benign vascular tumor composed of angioblastic cells. The adrenal
      gland localization is very rare, with only fifty cases reported in literature. We
      report a case of adrenal gland hemangioma diagnosed in a 55-year-old woman who
      presented a cervical neoplasm. The non-specific imaging features, the tumor size
      and the clinical context led to mandatory surgical resection. The pathological
      examination established the diagnosis of adrenal gland hemangioma.

PMID- 17194978
TI  - [The "Health watch mission" in France: expertise and evaluation].

PMID- 17194979
TI  - [Comparison of the French DRG based information system (PMSI) with the National
      Mesothelioma Surveillance Program database].
AB  - BACKGROUND: One of the main purposes of the French National Mesothelioma
      Surveillance Program is to estimate and follow the national incidence of pleural
      mesothelioma. We wanted to study the contribution of the French hospital national
      database as a valid source of mesothelioma incident cases. METHODS: From the 1998
      and 1999 hospital national database, medical records with a diagnosis code of
      mesothelioma or pleural cancer where selected among patients who resided in one
      of the 17 administrative divisions covered by the National Mesothelioma
      Surveillance Program in 1998. From these records, 506 patients in 1998 and 474
      patients in 1999 where identified and matched with the National Mesothelioma
      Surveillance Program cases over the same period using indirect criteria of
      identification (sex, age, place of residence). Medical records of cases unknown
      by the National Mesothelioma Surveillance Program where consulted in one of the
      administrative divisions. RESULTS: Only two-thirds of the registered cases of the
      National Mesothelioma Surveillance Program could be matched with a patient
      identified in the hospital national database with a diagnosis of mesothelioma
      registered during the same year. Consultation of the medical records showed that
      1) certified cases registered in the National Mesothelioma Surveillance Program
      where often (83%) found in the hospital national database with a code of
      mesothelioma but 10 to 15% of the patients with a code of mesothelioma in the
      national hospital databases had a different diagnosis according to their medical
      records; 2) 65% of the patients with a code of mesothelioma in the national
      hospital databases that where unknown from the National Mesothelioma Surveillance
      Program in 1998 and 55% in 1999 where prevalent cases; 3) 3 suspected cases had
      not been reported to the National Mesothelioma Surveillance Program. CONCLUSION:
      Because of lack of diagnosis certification, mistakes in encoding diagnosis and
      the fact that incident and prevalent cases cannot be distinguished in the
      hospital national database make it impossible to estimate the mesothelioma
      incidence solely from this source of data. However, the hospital claim databases
      constitute a complementary source of information for the active search of
      incident cases performed by the National Mesothelioma Surveillance Program.

PMID- 17194980
TI  - [Poverty and sociocultural factors in the use of maternal health services in
      Ivory Coast].
AB  - BACKGROUND: Better health for populations is linked to the adequate access to
      health services. This is particularly important in developing countries, where a
      number of economic, social, and geographic barriers exist. Pregnant women are
      particularly at risk, as they have many health needs and problems. In addition,
      the use of maternal health services is particularly influenced by economic and
      socio-cultural factors. Therefore, we intended to appreciate the association
      between poverty, socio-cultural factors and use of maternal health services in
      Ivory Coast. METHODS: For this study, our data were from the demographic and
      health survey in Ivory Coast in 1998. We used the logistic regression models to
      analyze the relation between poverty, socio-cultural factors and use of services
      (antenatal care, type of delivery). RESULTS: 62.4% of women used antenatal care
      adequately and 48.9% delivered in good conditions. Poverty is strongly linked to
      the use of services whatever the socio-cultural and demographic aspects are, with
      the poor using less services than the richer. Concerning the impact of socio
      cultural characteristics, women living alone or with one adult (OR=1.60; 95%
      IC=1.06-2.42), those who are Christian (OR=1.83; 95% IC=1.25-2.67) or Akan are
      more likely to have adequate antenatal care than women living with 5 adults or
      more, having traditional or no religion, and those who are Senoufo or non
      Ivorian. Besides, when the number of children increases, they are less likely to
      consult. Primiparous, Christians (OR=2.45; 95% IC=1.68-3.59) or Muslims (OR=1.73;
      95% IC=1.10-2.72) are more likely to deliver in a health center with a qualified
      assistance. CONCLUSION: Poverty has a negative effect on the use of maternal
      services but one should also take into account certain socio-cultural
      characteristics, namely number of adults in the household, parity, ethnicity and
      religion. While reducing poverty, it appears important to involve family members
      and religious or ethnic leaders in order to improve this use.

PMID- 17194981
TI  - [Evaluation of rational prescribing and dispensing of medicines in Mali].
AB  - Pharmaceutical policy in Mali is based on the concept of essential medicines and
      procurement of generic medicines. Unfortunately, increasing availability of
      generic medicines via different promotional programs can often be accompanied by
      their irrational use. This survey was thus designed to evaluate rational
      prescribing and dispensing of medicines in Mali. A cross-sectional survey was
      conducted from 1998 to 2005 in 30 primary health centers and 30 private
      dispensaries; in Bamako and in 6 of the 8 other regions of the country. In each
      of the visited facilities, 20 prescriptions dispensed at the time of the survey
      were collected. The average number of medicines per prescription was 3.2+/-1.3
      and 2.8+/-1.2 respectively in the public and private sectors. Medicines were
      prescribed under generic name in 88.2% of the public sector prescriptions and in
      30.9% of the private sector ones. Antibiotics were prescribed in 70.4% of the
      public sector prescriptions and in 50.0% of the private sector prescriptions. In
      the public sector 33.2% of the prescriptions had injections compared with 14.3%
      in the private sector (p<0.001). The median price per prescription was lower in
      the public sector (1575.0 CFA F, or 2.4 Euros, of which 91.3% were actually
      purchased by the patient) than in the private sector (5317.5 CFA F, or 8.1 Euros,
      of which 84.6% were purchased). Generic medicines are being used in the public
      sector but less frequently than in private practice. As therapeutic guidelines
      are already available, it would be useful to institute interactive information
      for practitioners through intensive visits by more experienced supervisors. The
      quality of the prescriptions could thus be optimized.

PMID- 17194982
TI  - Introduction of an obstetric health information system: results of a pilot study
      in North Cameroon.
AB  - BACKGROUND: International safe motherhood programs have placed increasing
      emphasis on assessing progress in reducing maternal mortality in developing
      countries. We assess the feasibility and relevance of an obstetric health
      information system introduced in Maroua urban district in North Cameroon.
      METHODS: During the study period, an obstetric observation register was
      introduced for obstetric data collection, complemented by anthropological case
      studies on maternal deaths. RESULTS: At the end of the study period,
      implementation and data collection processes were correctly done, and the overall
      rate of completion of obstetric registers was 95% (ranging from 82.5% to 98.5%
      between maternity units). Eight hundred and twenty-six deliveries (n=826) were
      recorded and evenly distributed over the nine weeks of the study period. Eight
      women (1%) were transferred from non-surgical to surgical health facilities.
      Thirteen C-sections (n=13; 1.6%; CI: 0.8-2.7%) mainly in the provincial hospital
      of Maroua (11/13), and four maternal deaths were recorded, giving a maternal
      mortality rate of 4/826 (484 for 100,000; CI: 132-1240 for 100,000 deliveries).
      Nevertheless, anthropological enquiry recorded five maternal deaths during the
      same study period. Analysis of the geographical origin of these women showed that
      four of the five came from very remote areas. Rapid analysis and dissemination of
      results have initiated changes in obstetric practices (introduction of the
      partograph, modifications in the attitudes of health personnel), and also to the
      creation of a network between maternity units (those with and without surgical
      facilities) and provincial health headquarters. CONCLUSION: The introduction and
      use of a basic obstetric health information system combined with anthropological
      survey can provide a relatively accurate assessment of the maternal health
      situation. Such knowledge would be an excellent basis for implementing obstetric
      networking and relevant tools for active management of the obstetric pyramid at a
      regional level in developing countries.

PMID- 17194983
TI  - [Prevalence of pressure sores in a university hospital in 2003].
AB  - BACKGROUND: To determine the prevalence of pressure sores in a university
      hospital and to assess the risk of developing a pressure sore. METHODS: A one-day
      survey was performed in all hospitalized patients, day hospital excepted. The
      Garches scale was used to assess the severity of pressure sores and the Braden
      scale was used to measure the patient's risk for the development of pressure
      ulcers. RESULTS: One thousand six hundred and eleven patients were included, mean
      age was 62+/-23 years and 53.3% were over 65 years old. In hospitalized patients,
      64% were in acute care, 29% in intermediate medicine and long-term care and 7% in
      intensive care units. We have found 675 pressure sores in 268 patients, mean age
      of 76 years; 263 decubitus ulcers were acquired during hospitalization. The most
      frequent sites were heels (46%) and sacrum (26%). Stage 1 pressure ulcers showed
      33% of the total. The total prevalence was 16.6%, 95% CI (14.9-18.6), the
      hospital acquired pressure sores prevalence was 7.5%, all stages included. A
      Braden score less than or equal to 15 was found in 29.1% of hospitalized
      patients. Standard mattresses were used in 37% of patients with pressure sores.
      Multivariate analysis showed that age and a Braden score less than or equal to 15
      were significantly associated with pressure sores. CONCLUSION: Pressure sores are
      still an important problem in hospital; occurrence must be considered as an
      iatrogenic event and management requires a multidisciplinary approach.

PMID- 17194985
TI  - [Pregnancy-related deaths. Genesis of the concept and methodological aspects].
AB  - Within the past 10 years, the outlook on the causes underlying maternal deaths
      has evolved, with the advent in the last "International classification of
      diseases" of the concepts of late maternal mortality and pregnancy-related
      mortality. Those concepts have led to an enlargement of the field, in terms of
      the range of causes as well as of the length of the time period at risk. Causes
      of death traditionally considered as "fortuitous" are now included in the count,
      given that the notion of pregnancy-related mortality covers all deaths occurring
      during pregnancy or at the latest one year after pregnancy termination, whatever
      the cause. Given this background, we critically review the definitions and
      classification systems of deaths of pregnant or post-partum women, and discuss
      the philosophy underlying these conceptual changes, and their consequences in
      terms of data collection and measurement issues.

PMID- 17194984
TI  - [Influence of a priori parameters on bayesian relative risks estimations. Spatial
      distribution of bladder cancer in the urban area of Grenoble].
AB  - Bayesian estimates of disease relative risks is currently the gold standard in
      disease mapping when the disease is rare and/or when the geographical area is
      small. Its use has become quite easy with adhoc software. However, the implicit
      mechanisms of the choices made by the user must be clearly identified. We were
      interested here in the consequences of the choice of the hyper a priori
      parameters. We have compared results obtained using various hyper a priori
      parameters. The consequences of these choices are illustrated through the example
      of the incidence of bladder cancer among men in the urban area of Grenoble. We
      show that the risks can appear weak from a statistical point of view but
      important from an epidemiologic point of view in the presentation of the results.

PMID- 17194986
TI  - [Bio-banks: changes arising from the new bioethics law].

PMID- 17194987
TI  - [Factors related to early abandon of the health care profession: confirmation of
      impact at one year. The Press/Next longitudinal survey].

PMID- 17194989
TI  - [Where are we going with bisphosphonates?].

PMID- 17194992
TI  - [Osteonecrosis of the jaws associated with bisphosphonates: five cases].
AB  - INTRODUCTION: Bisphosphonates have been recently associated with bone necrosis of
      jaws. PATIENTS AND METHOD: Five patients were treated, two males and three
      females. All patients received bisphophonates and chemotherapeutic agents, two
      for multiple myeloma and three for breast cancer with bone metastasis.
      Bisphophonates were discontinued. None of the patients had received radiotherapy
      to the head and neck. The localization was mandibular in four patients and the
      maxillary area in one with oro-antral fistula. Histological and microbiological
      studies were performed. RESULTS: Histopathology demonstrated osteonecrosis and
      ruled out detectable neoplastic disease of the jaws. Four biopsies showed
      Actinomycosis. Four patients underwent sequestrectomy, but the mucosa did not
      heal. DISCUSSION: Two mechanisms are involved: the antiangiogenic effect of
      bisphophonates has recently been described in vivo; as bone mineralization
      increases, accumulation of microdamage is observed in animals studies. Only the
      jaws are affected by bone necrosis, suggesting a possible trophism for
      bisphosphonate uptake? Other risks factors have been found: cancer, use of
      chemotherapeutic agents or corticosteroids, renal failure, Actinomycosis
      infection. The only effective treatment is dental prevention before starting
      treatment.

PMID- 17194994
TI  - [Wound healing effect of Eludril in a model of human gingival mucosa].
AB  - INTRODUCTION: The aim of this study was to evaluate and to compare the potential
      for wound healing of the buccal mucosa with the use of two mouth rinses; one
      containing 0.10% chlorhexidine with alcohol, the second containing 0.12%
      chlorhexidine without alcohol. MATERIAL AND METHOD: Using a model of human buccal
      mucosa kept alive ex vivo, an immunohistochemical assessment of the mitotic
      potential of epithelial cells and a biochemical evaluation of the capacity of the
      fibroblasts of the gingival mucosa to synthesize collagen was performed. RESULTS:
      A mouth rinse containing 0.10% chlorhexidine with alcohol (Eludril) did not alter
      the potential for epithelial proliferation and for collagen synthesis within the
      gingival chorion grown in survival conditions. The results revealed a significant
      difference between the two mouth rinses for each of the parameters studied. The
      most favourable results were obtained with the mouth rinse containing alcohol.
      DISCUSSION: The presence of alcohol in a mouth rinse containing 0.10%
      chlorhexidine has no deleterious effects on healing capacity. On the contrary, it
      helps stimulate wound healing. The combination of chlorhexidine plus alcohol is
      superior for healing, chlorhexidine alone does not show any significant
      difference compared with the control.

PMID- 17194993
TI  - [Bisphosphonates and maxillo-mandibular osteo(chemo)necrosis].
AB  - INTRODUCTION: Maxillo-mandibular osteonecrosis is exceptional outside a context
      of cervico-facial radiotherapy. Bisphosphonates are non-metabolized pyrophosphate
      analogues which inhibit osteoclastic activity. Bisphosphonates are prescribed for
      the treatment of malignant hypercalcemia, osteolysis associated with metastatic
      bone disease, Paget's disease and osteoporosis. Maxillomandibular osteonecrosis
      with bisphosphonates can be observed in 1/10000 patients, but is probably
      underestimated due to lack of dental examination. MATERIAL AND METHODS: We
      describe six cases of mandibular necrosis associated with bisphosphonates: five
      of them as part of their treatment regimen for a neoplastic condition and one for
      osteoporosis. RESULTS: Two patients developed spontaneous bone necrosis. In two
      others, tooth extraction preceded the onset of osteonecrosis. In the last two
      patients, we noted a preexisting dental infection. All the histopathological
      examinations showed necrotic bone colonized by Actinomyces. DISCUSSION:
      Bisphosphonate-induced osteonecrosis is only found in the maxillomandibular area
      because the jaws are the only bone in the skeleton exposed to the external
      environment. The mandible is rendered particularly prone to necrosis even after
      minor trauma because of its terminal vascularization. Careful oral examination is
      recommended before prescribing bisphosphonate therapy.

PMID- 17194996
TI  - [A proposed algorithm for medicodental care of patients treated with
      bisphosphonates].
AB  - Bisphophonates (BP) were first named diphosphonates. They are potent inhibitors
      of osteoclastic activity and so reduce bone remodeling. Additionally they have
      anti-angiogenic properties and contribute to progressive disappearance of bony
      micro-vascular blood supply. Administrated orally, BP are generally used to
      prevent and treat osteoporosis. Injectable BP are used in patients with multiple
      myeloma and metastatic solid tumors. Scientific evidence dealing with a
      potentially devastating side effect of BP, osteochemonecrosis of the jaws, is
      growing rapidly. Clinical signs and symptoms include absent or delayed soft
      tissue healing with bony exposure following dental extraction or spontaneous gum
      dehiscence. Patients are usually asymptomatic but may develop pain if the bone
      becomes secondarily infected. At the beginning, no radiographic manifestations
      are seen, but in some cases a vast zone of necrotic bone can be seen on MRI,
      larger than what could be expected. Surgical debridements, bone curettage, local
      irrigation and or hyperbaric oxygen therapy have proven to be unsuccessful. Up to
      now, no definitive treatment strategy has been published to manage those patients
      leaving the dentist or the stomatologist resourceless. This article proposes
      recommendations for general practitioners, dentists, oral surgeons and designed
      for three types of patients: 1. patients to be treated with BP; 2. patients
      treated with BP without bisphosphonate-associated osteonecrosis; 3. patients with
      bisphosphonate-associated osteonecrosis. The proposed guidelines are not
      definitive and practitioners remain free to choose their treatment. Of upmost
      importance is to recognize the risks of oral complications before, during and
      after surgery in patients treated with BP and to inform them of such risks.

PMID- 17194995
TI  - [Surgical treatment of temporomandibular joint: apropos of 94 cases].
AB  - INTRODUCTION: The temporomandibular joint (TMJ) is a complex entity subjected to
      repeated stress with several symptoms. About one-third of people have at least
      one of those symptoms but only few (3 to 7%) need treatment. The aim of this
      retrospective study was to evaluate the results of temporomandibular joint
      surgery in 94 patients. PATIENTS AND METHODS: Several data were used for decision
      making and the surgical technique was adapted to the etiology. The type of
      postoperative physiotherapy performed depended on the type of pathology. RESULTS:
      Most patients who underwent surgery between 1989 and 2004 were women (83%). The
      mean age was 30 years. We performed 179 surgical procedures and among them 151
      Dautrey procedures. In 28 cases miniplates were used to avoid recurrences. In 57
      cases postoperative physiotherapy was performed. The mean postoperative mouth
      opening increase was 4.7 mm (+ 23%). There was no infection or lost of plate. The
      mean of follow-up was about 14 months. DISCUSSION: With a long follow-up and an
      acceptable number of patients and operations, this retrospective study
      demonstrated the effectiveness of the Dautrey procedure in TMJ subluxations.

PMID- 17194997
TI  - [Treatment of drooling: review of the literature].
AB  - An exhaustive review of the literature shows the very relative efficiency of
      diverse treatments for chronic drooling. Morbidity is too high with medical
      treatments and behavioral treatments require active collaboration from the
      patient. The different surgical techniques, either based on derivation or
      ligature of the principal salivary ducts combined with glandular tissue
      extirpation, are not free of complications. There is much controversy over their
      efficiency due to the lack of sound evidence. Caution is therefore primordial
      before proposing surgery for chronic drooling: the available surgical procedures
      all have technical limitations and clinical trials have demonstrated many
      failures. At the most, the patient can expect a 50 to a maximum 80% reduction of
      drooling.

PMID- 17194998
TI  - [Modified Risdon approach for the treatment of subcondylar fractures of the
      mandible].

PMID- 17194999
TI  - [The transitional bridge in early implant loading: history, design, installation,
      perspectives].
AB  - The progress made in implantology since the work of Pr. Branemark has led to the
      development of early functional implant loading. This satisfies one of our
      patients' primary goals: restoration of fixed dentition as quickly as possible.
      This article describes the history, design, installation technique, and
      perspectives for the transitional prosthesis, the most important component of
      this early loading concept.

PMID- 17195000
TI  - [Monitoring free flaps with cutaneous microdialysis: preliminary study in oral
      cavity reconstruction].
AB  - INTRODUCTION: Postoperative monitoring of free flaps with microdialysis allows
      early diagnosis of anastomotic complications. Feasibi-lity studies are required
      to examine flap accessibility for oral cavity reconstruction. CASES: We present
      our preliminary findings in two patients who underwent radial free flap
      reconstruction of the floor of the mouth. For the first patient, a microprobe was
      used to monitor the flap for 45 hours. In the second case, an abdominal
      microprobe served as a control in healthy skin with another probe located in the
      cutaneous flap for 4 days. Flap monitoring, starting from the recovery room, was
      successful with easy manipulations for the nurse. Correlation between the
      monitoring curves and the clinical aspect of the flap was excellent. DISCUSSION:
      The microprobe should be short (1 cm), and carefully anchored. Naso-gastric
      feeding is required during monitoring. A close correlation has been found between
      glucose level and systolic pressure. The use of a comparative microprobe in
      healthy abdominal skin is helpful in learning to use the dialysis curves.

PMID- 17195001
TI  - [Mandibular Langerhans cell histiocytosis].
AB  - INTRODUCTION: Langerhan's cell histiocytosis is defined as an abnormal
      proliferation of Langerhans cells in various organs and tissues (bone, skin,
      lymph nodes...). Among facial locations, mandibular involvement is the most
      frequent and occurs in young people less than 20 years. The aim of this report is
      to review the characteristic features of this disease, the current means of
      diagnosis and treatment through two case reports. CASES: Two male patients aged
      10 and 55 years respectively presented with single mandibular location of
      Langerhans cell histiocytosis. The diagnosis was confirmed by histological
      examination of the biopsy specimen. The first patient underwent surgical
      resection of the tumor. No recurrence was observed. In the second patient, the
      postoperative course was marked by the appearance of an inflammatory phenomenon
      in the adjacent skin and mucosa, successfully treated by intralesional
      corticosteroid therapy. DISCUSSION: Langerhan's cell histiocytosis is a rare
      disease. The mandibular location has variable clinical expressions which can vary
      from dental mobility to tumor development in the gingiva. The radiological
      appearance is also variable; histological proof is required for diagnosis.
      Treatment depends on the number and locations of the lesions. In case of a single
      location, the treatment options may vary from a "wait and see" attitude to a non
      aggressive surgery, with a possible local corticosteroid therapy or radiothe
      rapy. For multiples locations, chemotherapy is indicated.

PMID- 17195002
TI  - [Desmoid tumor of the parotid gland].
AB  - INTRODUCTION: Desmoid tumor is a benign microscopic tumor that belongs to the
      group of the deep fibromatosis. It usually arises from facial or
      musculoaponeurotic structures in the abdomen but rarely is located in the head or
      neck. Locally, it is characterized by a massive invasion with strong potential
      for recurrence. CASE REPORT: A 37-year-old woman was hospitalized for a swelling
      of the left parotid gland region which had progressed for eight years. Physical
      examination revealed a tumor in the parotid gland, which was hard and adherent
      deeply, measuring 4 cm/3 cm and sensitive to palpation; without satellite nodes
      nor facial paralysis. The treatment consisted in a superficial parotidectomy.
      Pathology was in favor of a desmoid tumor. After an 18-month follow-up, the
      patient is healthy without any sign of recurrence. DISCUSSION: Desmoid tumors are
      deep fibromatosis characterized by their slow growth and especially by
      considerable infiltration of the adjacent structures but without potential for
      metastasis. Although very rare, the cervical localizations are especially
      aggressive. This clinical case illustrates the clinical features of this rare
      affection and offers matter for discussion of therapeutic difficulties.

PMID- 17195003
TI  - [Primary malignant melanoma of the nasal cavity presenting as a large tumor of
      the cheek].
AB  - INTRODUCTION: Malignant melanoma of the nasal cavity is a rare tumor usually
      causing unilateral nasal obstruction and nasal bleeding. Diagnosis is achieved
      with immunohistochemistry analysis. Surgery is proposed for curative treatment.
      CASE REPORT: We report the case of a 60-year-old man with a malignant melanoma of
      the nasal cavity revealed by an important tumor of the cheek. Epistaxis and nasal
      obstructive syndrome occurred later. Because of the tumor stage, palliative
      chemotherapy was performed but the patient died 4 months after the diagnosis.
      DISCUSSION: This clinical presentation of malignant melanoma of the nasal cavity,
      related to local spreading, is exceptional. CT scan and MRI are essential for
      tumor staging and therapeutic decision-making. Prognosis remains poor.

PMID- 17195004
TI  - [Syndromic gingival fibromatosis].
AB  - INTRODUCTION: Gingival fibromatosis is an inherited disease of the gingival
      tissue causing proliferative fibrous lesions occurring alone or as one feature of
      a more widespread syndrome. OBSERVATION: A 26-year-old girl consulted the oral
      surgery department for a functional problem due to the presence of two tumor
      masses located in the palate. The histological diagnosis was gingival
      fibromatosis. The presence of skeletal disorders in this patient with gingival
      fibromatosis suggested the diagnosis of Zimmermann Laband syndrome. DISCUSSION:
      Gingival fibromatosis is a rare condition characterized by a gingival
      hypertrophy. It is transmitted by autosomal dominant or recessive inheritance.
      The oral examination and histology provides the diagnosis. The treatment
      consistes of surgical removal of the hyperplasic fibrous tissue. Prognosis is
      dominated by the risk of recurrence which is frequent. Generally, gingival
      fibromatosis is isolated. In rare cases, it can be associated with symptoms
      sugges-ting a syndromic diagnosis such as Zimmermann Laband syndrome. In addition
      to gingival hypertrophy, skeletal anomalies can involve the fingers, the
      toenails, the thorax or the vertebrae. Splenomegaly and joint hyperextensibility
      can also be found.

PMID- 17195005
TI  - [Brown tumor of the jaws].

PMID- 17195006
TI  - [Synovial osteochondromatosis of the temporomandibular joint].

PMID- 17195007
TI  - [Cervico-facial rejuvenation: treatment plan and key points for surgery].

PMID- 17195011
TI  - Inhibition of histone deacetylation promotes abnormal epidermal differentiation
      and specifically suppresses the expression of the late differentiation marker
      profilaggrin.
AB  - Reversible protein acetylation modulates higher-order chromatin structure and
      transcription activity of the genome. The reversible acetylation is executed by
      the intrinsic acetylase and deacetylase activities of co-regulators associated
      with the regulatory regions. Compounds capable of inhibiting deacetylase activity
      are a powerful tool for dissecting the role of protein acetylation in gene
      function. The ability of the deacetylase inhibitors to preferentially affect the
      homeostasis of transformed cells has also prompted studies for their clinical
      application. We present evidence that deacetylase inhibition with trichostatin A
      (TSA) affects the normal epidermal tissue architecture and pattern of expression
      by a mechanism(s) that does not correlate directly with the hyperacetylated
      histone status. While promoting abnormal differentiation, TSA specifically
      represses transcription initiation of the differentiation marker profilaggrin.
      Multiple factors, among which we have identified decreased Sp1 binding, a local
      decrease in acetylation activity, and enhanced synthesis and recruitment of a
      repressor histone demethylase, alter the chromatin configuration over the
      promoter, ultimately blocking its activation by c-jun. As compromised
      profilaggrin production leads to epidermal and consequently allergic disorders,
      our findings emphasize the need for a detailed investigation of the role
      deacetylase inhibitors may play in the maintenance of epidermal homeostasis in
      order to optimize their clinical applicability.

PMID- 17195012
TI  - The alpha and beta subunits of the metalloprotease meprin are expressed in
      separate layers of human epidermis, revealing different functions in keratinocyte
      proliferation and differentiation.
AB  - The zinc endopeptidase meprin (EC 3.4.24.18) is expressed in brush border
      membranes of intestine and kidney tubules, intestinal leukocytes, and certain
      cancer cells, suggesting a role in epithelial differentiation and cell migration.
      Here we show by RT-PCR and immunoblotting that meprin is also expressed in human
      skin. As visualized by immunohistochemistry, the two meprin subunits are
      localized in separate cell layers of the human epidermis. Meprin alpha is
      expressed in the stratum basale, whereas meprin beta is found in cells of the
      stratum granulosum just beneath the stratum corneum. In hyperproliferative
      epidermis such as in psoriasis vulgaris, meprin alpha showed a marked shift of
      expression from the basal to the uppermost layers of the epidermis. The
      expression patterns suggest distinct functions for the two subunits in skin. This
      assumption is supported by diverse effects of recombinant meprin alpha and beta
      on human adult low-calcium high-temperature keratinocytes. Here, beta induced a
      dramatic change in cell morphology and reduced the cell number, indicating a
      function in terminal differentiation, whereas meprin alpha did not affect cell
      viability, and may play a role in basal keratinocyte proliferation.

PMID- 17195013
TI  - Matrix metalloproteinase-19 expression in keratinocytes is repressed by
      transcription factors Tst-1 and Skn-1a: implications for keratinocyte
      differentiation.
AB  - Matrix metalloproteinase-19 (MMP-19), unlike other members of the MMP family, is
      expressed in basal keratinocytes of intact epidermis whereas keratinocytes in
      suprabasal and higher epidermal layers express this enzyme only during cutaneous
      disorders. As the activity of MMP-19 effects proliferation, migration, and
      adhesion of keratinocytes we examined whether transcription factors involved in
      keratinocyte differentiation repress the expression of MMP-19. Using luciferase
      reporter assays, POU transcription factors Tst-1 (Oct-6) and Skn-1a (Oct-11)
      markedly downregulated the activity of MMP-19 promoter in COS-7 cells and HaCaT
      keratinocytes. Tst-1 alone was able to inhibit 85% of the promoter activity. Skn
      1a exhibited a weak inhibitory effect although it synergistically increased
      effects of Tst-1. HaCaT cells stably transfected with Tst-1 showed a strong
      decrease of activity of MMP-19 promoter that correlated with suppression of MMP
      19, cytokeratin 14 and 5, decreased cell proliferation, and altered expression of
      involucrin and loricrin. The expression of MMP-9 was also significantly reduced
      in Tst-1 expressing keratinocytes. MMP-2 was substantially affected during its
      activation whereas the expression of MMP-28 was unchanged. Our results suggest
      that Tst-1 and Skn-1a regulate expression of MMPs in keratinocytes and effect
      both the expression and activation of these proteolytic enzymes.

PMID- 17195014
TI  - Increased ICAM-1 expression causes endothelial cell leakiness, cytoskeletal
      reorganization and junctional alterations.
AB  - Tumor necrosis factor (TNF)-induced ICAM-1 in endothelial cells (EC) promotes
      leukocyte adhesion. Here we report that ICAM-1 also effects EC barrier function.
      Control- or E-selectin-transduced human dermal microvascular EC (HDMEC) form a
      barrier to flux of proteins and to passage of current (measured as
      transendothelial electrical resistance or TEER). HDMEC transduced with ICAM-1 at
      levels comparable to that induced by TNF show reduced TEER, but do so without
      overtly changing their cell junctions, cell shape, or cytoskeleton organization.
      Higher levels of ICAM-1 further reduce TEER, increase F/G-actin ratios, rearrange
      the actin cytoskeleton to cause cell elongation, and alter junctional zona
      occludens 1 and vascular endothelial-cadherin staining. Transducing with ICAM-1
      lacking an intracellular region also reduces TEER. TNF-induced changes in TEER
      and shape follow a similar time course as ICAM-1 induction; however, the fall in
      TEER occurs at lower TNF concentrations. Inhibiting NF-kappaB activation blocks
      ICAM-1 induction; TEER reduction, and shape change. Specific small-interfering
      RNA knockdown of ICAM-1 partially inhibits TNF-induced shape change. We conclude
      that moderately elevated ICAM-1 expression reduces EC barrier function and that
      expressing higher levels of ICAM-1 affects cell junctions and the cytoskeleton.
      Induction of ICAM-1 may contribute to but does not fully account for TNF-induced
      vascular leak and EC shape change.

PMID- 17195015
TI  - Suppression of spontaneous dermatitis in NC/Nga murine model by PG102 isolated
      from Actinidia arguta.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease, which requires
      safe and effective pharmacological therapy. We previously found that two
      preparations from Actinidia arguta, PG102T, and PG102E, could modulate Th1/Th2
      pathways and suppress IgE biosynthesis. This study was performed to assess the
      therapeutic effects of PG102T and PG102E on the development of dermatitis in
      NC/Nga mice, characterized by the spontaneous onset of AD along with an elevated
      level of IgE under conventional conditions. PG102T or PG102E administration
      significantly reduced dermatitis severity as well as scratching tendency in
      conventional mice. The suppression of dermatitis by PG102 was accompanied by a
      decrease in the plasma level of IgE, IgG1, and IL-4 and also by an increase in
      that of IgG2a and IL-12. The splenic level of IL-4, IL-5, and IL-10 was
      downregulated, whereas that of IFN-gamma and IL-12 was increased. The number of
      eosinophils and the expression of eotaxin and thymus and activation-regulated
      chemokine were decreased by PG102T or PG102E. Histological findings also
      indicated that the thickening of epidermis/dermis and the dermal infiltration of
      inflammatory cells including mast cells were greatly inhibited. These data
      suggest that PG102 may be effective therapeutic agents for the treatment of AD.

PMID- 17195016
TI  - Calcium-independent desmosomes of keratinocytes are hyper-adhesive.
AB  - Desmosomes in tissues are resistant to disruption by chelation of extracellular
      calcium. It has been suggested that this represents a hyper-adhesive state of
      these intercellular junctions that is crucial for the maintenance of epidermal
      integrity. Desmosomes change to a lower affinity, calcium-dependent adhesive
      state when cells are cultured at low density or when an intact epithelial cell
      sheet is wounded. Here we demonstrate that cells of the immortalized human
      keratinocyte line HaCaT acquire calcium-independent desmosomes in confluent
      culture. An adhesion assay shows that HaCaT cells with calcium-independent
      desmosomes are more cohesive than cells with calcium-dependent desmosomes. This
      assay relates directly to desmosomal adhesion because it involves splitting of
      the desmosomal adhesive material. Moreover, the difference in adhesiveness
      between calcium-dependent and calcium-independent desmosomes involves no
      quantitative change in the known protein composition of desmosomes. Instead,
      switching between the two adhesive states can be achieved by activation or
      inhibition of protein kinase C (PKC), suggesting a direct effect of PKC
      signalling on desmosomal adhesion. These results provide direct support for the
      concept of hyper-adhesiveness in desmosomes.

PMID- 17195017
TI  - BRET analysis of GPCR oligomerization: newer does not mean better.

PMID- 17195019
TI  - ProteomeBinders: planning a European resource of affinity reagents for analysis
      of the human proteome.
AB  - ProteomeBinders is a new European consortium aiming to establish a comprehensive
      resource of well-characterized affinity reagents, including but not limited to
      antibodies, for analysis of the human proteome. Given the huge diversity of the
      proteome, the scale of the project is potentially immense but nevertheless
      feasible in the context of a pan-European or even worldwide coordination.

PMID- 17195020
TI  - 4D brain signaling.

PMID- 17195021
TI  - From cryo-EM, multiple protein structures in one shot.

PMID- 17195023
TI  - Abstracts of the 5th Asian-Pacific Organization for Cell Biology (APOCB)
      Congress, October 28-31, 2006, Beijing, China.

PMID- 17195033
TI  - Inhaling medicines: delivering drugs to the body through the lungs.
AB  - Remarkably, with the exception of anaesthetic gases, the ancient human practice
      of inhaling substances into the lungs for systemic effect has only just begun to
      be adopted by modern medicine. Treatment of asthma by inhaled drugs began in
      earnest in the 1950s, and now such 'topical' or targeted treatment with inhaled
      drugs is considered for treating many other lung diseases. More recently, major
      advances have led to increasing interest in systemic delivery of drugs by
      inhalation. Small molecules can be delivered with very rapid action, low
      metabolism and high bioavailability; and macromolecules can be delivered without
      injections, as highlighted by the recent approval of the first inhaled insulin
      product. Here, we review these advances, and discuss aspects of lung physiology
      and formulation composition that influence the systemic delivery of inhaled
      therapeutics.

PMID- 17195035
TI  - Lipid raft microdomains and neurotransmitter signalling.
AB  - Lipid rafts are specialized structures on the plasma membrane that have an
      altered lipid composition as well as links to the cytoskeleton. It has been
      proposed that these structures are membrane domains in which neurotransmitter
      signalling might occur through a clustering of receptors and components of
      receptor-activated signalling cascades. The localization of these proteins in
      lipid rafts, which is affected by the cytoskeleton, also influences the potency
      and efficacy of neurotransmitter receptors and transporters. The effect of lipid
      rafts on neurotransmitter signalling has also been implicated in neurological and
      psychiatric diseases.

PMID- 17195034
TI  - Biologic therapies in rheumatology: lessons learned, future directions.
AB  - During the past decade biologic therapies such as monoclonal antibodies and
      fusion proteins have revolutionized the management of rheumatic disease. By
      targeting key cytokines and immune cells biologics have provided more specific
      therapeutic interventions with less immunosuppression. Clinical use, however, has
      revealed that their theoretical simplicity hides a more complex reality.
      Efficacy, toxicity and even pharmacodynamic effects can deviate from those
      predicted, as poignantly illustrated by the catastrophic effects witnessed during
      the first-into-human administration of TGN1412. This review summarizes lessons
      gleaned from practical experience and discusses how these can inform future
      discovery and development of new biologic therapies for rheumatology.

PMID- 17195037
TI  - The systematic position of some nippostrongyline nematodes (Trichostrongylina:
      Heligmosomoidea) parasitic in Argentinean sigmodontine rodents.
AB  - The systematic position of two nippostrongyline nematodes described from
      Argentinean sigmodontine rodents is clarified. The first species,
      Hassalstrongylus multiovatus Suriano & Navone, 1992, parasitic in Akodon
      simulator Thomas from the province of Tucuman, was studied on the basis of type
      and voucher material. H. multiovatus is proposed as a junior synonym of
      Trichofreitasia lenti Sutton & Durette-Desset, 1991, a parasite described from
      Oligoryzomys flavescens (Waterhouse) in the province of Buenos Aires. The
      holotype and three of seven paratypes deposited as H. multiovatus were identified
      as T. lenti. One male paratype was identified as Guerrerostrongylus uruguayensis
      Sutton & Durette-Desset, 1991, a parasite described from O. flavescens in
      Uruguay. Three female paratypes were identified as Guerrerostrongylus sp. The
      second species, Stilestrongylus scapteromys Suriano & Navone, 1996, parasitic in
      Scapteromys aquaticus Thomas from the province of Buenos Aires, was studied on
      voucher material. Stilestrongylus scapteromys and Malvinema frederici Digiani,
      Sutton & Durette-Desset, 2003, the type-species of Malvinema Digiani, Sutton &
      Durette-Desset, 2003, were described from the same host and geographical region.
      As they are considered to refer to one and the same taxon, the new combination
      Malvinema scapteromys n. comb. is proposed for this species.

PMID- 17195036
TI  - Overexpression of TMAC2, a novel negative regulator of abscisic acid and salinity
      responses, has pleiotropic effects in Arabidopsis thaliana.
AB  - Phytohormone abscisic acid (ABA) regulates many aspects of plant development and
      growth. To explore the molecular mechanism of ABA, we identified the novel ABA
      regulated genes in Arabidopsis thaliana by searching for genes possessing two or
      more ABREs (ABA-responsive elements). One of these genes, two or more ABREs
      containing gene 2 (TMAC2) is highly induced by ABA and NaC1. Database searches
      revealed that TMAC2 encodes a protein with no domains of known function.
      Expression of TMAC2-GFP fusion protein in Arabidopsis mesophyll protoplasts
      indicated that TMAC2 is targeted to the nucleus. Although the gene has a basal
      level of expression in various Arabidopsis organs/tissues except for adult
      leaves, a high expression level was detected in roots. Constitutive
      overexpression of TMAC2 in plants resulted in the insensitivity to ABA and NaCl,
      suggesting that TMAC2 plays a negative role in ABA and salt stress responses.
      Furthermore, TMAC2-overexpressing plants exhibited the short roots, late
      flowering and starch-excess phenotypes. RT-PCR analysis showed that decreased
      expression of two floral- and one starch degradation-related genes, SOC1/AGL20
      and SEP3/AGL9, and SEX1, respectively, may lead to altered phenotypes of TMAC2
      overexpressing plants. Taken together, our data reveal that TMAC2 acts in the
      nucleus and is an important negative regulator of ABA and salt stress responses,
      and could play a critical role in controlling root elongation, floral initiation
      and starch degradation.

PMID- 17195038
TI  - [Cutaneous B-cell lymphoma. Classification and diagnostics].
AB  - Primary cutaneous B-cell lymphomas include cutaneous follicle centre lymphoma
      (PCFCL), cutaneous marginal zone B-cell lymphoma (PCMZL) and cutaneous diffuse
      large B-cell lymphoma (PCLBCL) "leg type" which are the three main types in the
      new WHO-EORTC classification for cutaneous lymphomas. PCFCL and PCMZL are
      indolent lymphomas with an excellent prognosis while PCLBCL shows an aggressive
      clinical course. All three types must be distinguished from a secondary skin
      involvement by systemic lymphomas. Since histological and immunohistochemical
      findings are not decisive, making this distinction requires appropriate staging
      procedures. In contrast, the pathologist can make an important contribution to
      the differential diagnosis between neoplastic and reactive cutaneous
      lymphoproliferations.

PMID- 17195039
TI  - [Mediastinal large B-cell lymphoma].
AB  - Mediastinal B-cell lymphoma is a locally highly aggressive tumour which was first
      described in the early 1980s. The incidence is about 2-3% of all non-Hodgkin's
      lymphomas. The conceptional evolution of this lymphoma entity was hampered by its
      low incidence and the broad spectrum of morphological variants present. However,
      since mediastinal B-cell lymphoma has distinct morphological, immunological,
      genetic, and clinical features, it has been listed in the revised European
      American Classification of Lymphoid Neoplasms (REAL-Classification) since 1994 as
      a variant of diffuse large B-cell lymphoma. In the World Health Organization
      classification of malignant lymphomas, mediastinal B-cell lymphoma is now listed
      with an own disease code (ICD-9679/3).

PMID- 17195040
TI  - [Peripheral NK/T-cell lymphoma].
AB  - Peripheral T-cell lymphomas comprise 8% of the malignant lymphomas in Germany.
      About 25% of these cases present primarily in extranodal localizations. Such
      localizations are typical for the respective disease and form the basis for the
      classification of extranodal peripheral T-cell lymphoma. The morphology,
      immunophenotype and lineage specificity of the tumor cells (originating from T-
      or NK-cells) is only secondary for the classification. Extranodal NK/T-cell
      lymphomas of the nasal type are characterized by an angiocentric growth pattern
      and large confluent areas of necrosis. In addition, there is a clonal infection
      by Epstein-Barr virus in the T-lymphocytes. In the differential diagnosis, B-cell
      lymphomas are more frequent at all localizations than T- or NK-cell lymphomas.

PMID- 17195041
TI  - [Follicular and mantle cell lymphoma. Extranodal involvement of primarily nodal
      indolent B-cell lymphomas].
AB  - Indolent (low-grade) B-cell non-Hodgkin's lymphomas, such as follicular and
      mantle cell lymphomas, are primarily nodal lymphomas in which lymph node
      involvement is the dominant clinical feature. The frequency of extranodal
      manifestations of these primarily nodal lymphomas is often underestimated. The
      typical growth pattern of nodal lymphomas can be absent or not evaluable because
      the biopsy specimens are often small in cases with extranodal involvement.
      Therefore, the immunophenotype of the lymphoma cells is of great importance for
      the diagnosis of indolent lymphomas with extranodal localizations.

PMID- 17195042
TI  - A laparoscopic duodenojejunostomy for a duodenal obstruction from lymphoma.
AB  - A patient with lymphoma in one-third of the duodenum causing a duodenal
      obstruction is described. The patient had a partial response with chemotherapy,
      but still was obstructed and unable to eat. He was losing weight, and
      chemotherapy had to be stopped. A gastrostomy tube was inserted for drainage
      because the stomach was quite distended. A jejunostomy tube was passed through
      the gastrostomy tube for feeding, but the patient did not tolerate the feeding. A
      laparoscopic bypass of the duodenumduodenal obstruction (from duodenum to
      jejunum) for this patient is shown on a video. The patient did very well after
      this bypass was provided. He was able to tolerate an oral diet on postoperative
      day 2, and on postoperative day 4, he was discharged home. He has since resumed
      chemotherapy, and is doing well, at this writing, 2 months after surgery.
      Electronic supplementary material is available for this article at
      http://dx.doi.org/10.1007/s00464-005-0874-2.

PMID- 17195043
TI  - Missouri casino self-excluders: distributions across time and space.
AB  - According to public health research, exposure to casinos is a risk factor for
      disordered gambling. Consequently, casino self-exclusion programs, which provide
      gamblers with the opportunity to voluntarily seek limits on their access to
      gambling venues, can serve as a barometer of the concentration of disordered
      gambling in an area. This study reports on the distribution, both temporally and
      geographically, of 6,599 people who applied to exclude themselves from Missouri
      casinos between November, 1996 and February, 2004. Analyses used Microsoft
      MapPoint to plot the location of casinos and self-excluders (SEs) across Missouri
      and its constituent counties. These regional exposure analyses showed that the
      Western region around Kansas City is an epicenter of disordered gambling as, to a
      lesser extent, is the Eastern region around St. Louis. The annual number of SE
      enrollments increased during the first few years of the Missouri self-exclusion
      program and then leveled off during the later years. These findings have
      important implications for public health and the development of public health
      interventions for disordered gamblers.

PMID- 17195044
TI  - Rosmarinic acid induces apoptosis of activated T cells from rheumatoid arthritis
      patients via mitochondrial pathway.
AB  - T cells play an important role in the initiation and the progression of
      rheumatoid arthritis (RA) and depletion of potentially pathogenic T cells was
      suggested as an important therapeutic protocol. We determined if rosmarinic acid
      (RosA), known as a secondary metabolite from herbal plants, had apoptotic
      activity toward T cells from RA patients and further verified target T-cell
      subsets. CD3(+)CD25(+) activated T-cell subsets from most of the RA patients
      displayed significantly higher apoptosis rates than did the PBMCs and total
      CD3(+) T cells. Furthermore, activated and effector CD4(+) T cells, including
      CD4(+)CD25(+) and CD4(+)CD45RO(+) T cells, had a tendency of being more
      susceptible to RosA-induced apoptosis than that of resting and naive T-cell
      subsets. RosA induced the release of cytochrome c from mitochondria and the
      blockage of mitochondrial depolarization inhibited apoptosis. Taken together,
      these results suggest that RosA induces apoptosis of activated T-cell subsets
      from RA patients via a mitochondrial pathway.

PMID- 17195046
TI  - Intrasellar malignant peripheral nerve sheath tumor (MPNST).
AB  - Intracranial malignant peripheral nerve sheath tumors (MPNST) and intrasellar
      schwannomas are rare tumors. We describe a case of an intrasellar schwannoma with
      progression to a MPNST, a finding that, although very rare, extends the
      differential diagnosis of intrasellar lesions.

PMID- 17195045
TI  - Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases
      suggests a shared mechanism of B-cell tolerance loss.
AB  - : We report here that dysregulation of CD19, a coreceptor that augments B-cell
      receptor (BCR) signaling, occurs at two B-cell differentiative stages in patients
      with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic
      autoantibody (ANCA) associated small vessel vasculitis (SVV). The naive B cells
      of nearly all SLE and ANCA-SVV patients express approximately 20% less CD19 than
      healthy control (HC) B cells. In contrast, a subset of memory B cells of some SLE
      and ANCA-SVV Pts (25-35%) express two to fourfold more CD19 than HC B cells.
      These CD19(hi) memory B cells are activated and exhibit evidence of antigen
      selection. Proteome array analysis of 67 autoantigens indicates that CD19(hi) SLE
      Pts exhibit a distinct autoantibody profile characterized by high levels of
      antibodies to small nuclear ribonucleoproteins and low levels of antiglomerular
      autoantibodies. These findings have implications for autoreactive B-cell
      activation and suggest a shared mechanism of B-cell tolerance loss in these two
      diseases.

PMID- 17195047
TI  - Francesco Rizzoli (1809-1880) and the elusive case of Giulia: the description of
      an "arteriovenous aneurysm passing through the wall of the skull".
AB  - The improved knowledge of the clinical and haemodynamical aspects of extracranial
      arteriovenous malformations in the 18th century provided a foundation for the
      understanding and treatment of cerebrovascular pathology. It was not until the
      late 19th century that detailed clinicopathological reports of intracranial
      arteriovenous malformations were published. A seminal report by the Italian
      surgeon Francesco Rizzoli described Giulia, a 9-year-old girl who presented with
      seizures and an occipital pulsanting swelling in 1873. Rizzoli used Giulia's
      signs and symptoms to predict the complex angioarchitecture of her "arteriovenous
      aneurysm passing through the wall of skull". Postmortem examination confirmed the
      supposed diagnosis, and showed a direct communication between the hypertrophic
      branches of the ocipital artery and the transverse sinus. The clinical course of
      that case is briefly reviewed in this article and the diagnosis of this unusual
      arteriovenous shunt is discussed in light of current neurosurgical knowledge.

PMID- 17195048
TI  - Indomethacin and cerebral autoregulation in severe head injured patients: a
      transcranial Doppler study.
AB  - OBJECTIVE: To assess the effect of indomethacin on cerebral autoregulation,
      systemic and cerebral haemodynamics, in severe head trauma patients. DESIGN:
      Prospective, controlled clinical trial, with repeated measurements. SETTINGS: A
      12-bed adult general intensive care unit in a third level referral university
      hospital. PATIENTS: 16 severely head injured patients, 14 males, age range 17-60.
      INTERVENTIONS: Indomethacin was administrated as a load plus continuous infusion.
      Indomethacin reactivity was assessed as the estimated cerebral blood flow change
      elicited by the load. Dynamic and static cerebral autoregulation tests were
      performed before indomethacin administration, and during its infusion.
      MEASUREMENTS AND MAIN RESULTS: Systemic and cerebral haemodynamic changes were
      assessed through continuous monitoring of mean arterial pressure, transcranial
      Doppler cerebral blood flow velocity, intracranial pressure, cerebral perfusion
      pressure, and jugular venous oxygen saturation. Indomethacin loading dose was
      immediately followed by a cerebral blood flow median decrease of 36 or 29% (p =
      ns) evaluated by two different methods, by an ICP decrease and by an AVDO(2)
      increase from 3.52 to 6.15 mL/dL (p = 0.002). Dynamic autoregulation increased
      from a median of 28 to 57% (p<0.05) during indomethacin infusion; static
      autoregulation also increased, from a median of 72 to 89% (p = ns). CONCLUSIONS:
      Indomethacin decreased intracranial pressure and cerebral blood flow, and
      increased cerebral perfusion pressure, while maintaining tissue properties of
      further extracting O(2). The increase in both autoregulatory values reveals an
      enhancement of cerebral microvasculature reactivity under indomethacin, during
      hypertensive and--especially--during hypotensive situations.

PMID- 17195049
TI  - Body indices and basic vital signs in Helicobacter pylori positive and negative
      persons.
AB  - It has been hypothesized that Helicobacter pylori (Hp) infection may contribute
      to reduced stature, risk of hypertension or obesity. The aim was to evaluate body
      indices in Hp positive and negative persons. A total of 2436 subjects (4-100
      years old) were tested for Hp status by (13)C-urea breath test. Data on height
      and weight were collected for 84%, and blood pressure for 80% of the study
      subjects. The prevalence of Hp infection was 41.6%. The odds ratio for a 10-year
      increase in age was 1.21 (95% CI 1.17-1.25, p-value <0.001). Statistically
      significant negative association of Hp positivity with body height was most
      pronounced in the younger age groups, while a positive association of Hp
      positivity with body mass index was only seen in those aged 15+ years. There was
      a negative effect of Hp positivity on systolic and diastolic blood pressure in
      subjects below 25 and a relatively strong positive effect on blood pressure in
      subjects over 65 years. Residual confounding by social characteristics as a
      possible explanation for the associations of Hp positivity with height and blood
      pressure cannot be excluded. Unmeasured factors related to social and family
      environment may cause the apparent association between Hp positivity and
      children's growth and blood pressure.

PMID- 17195050
TI  - Exercise participation and self-rated health: do common genes explain the
      association?
AB  - The purpose of this study is to investigate whether there is an association
      between exercise participation and self-rated health and whether this association
      can be explained by common genes and/or common environmental influences. In a
      sample of 5,140 Dutch adult twins and their non-twin siblings from 2,831
      families, exercise participation (sedentaries, light or moderate, vigorous
      exercisers) and self-rated health were assessed by survey. To investigate the
      etiology of the association, bivariate genetic models using structural equation
      modeling were applied to the data. The correlation between exercise participation
      and self-rated health is significant but modest (r = 0.20). Exercise
      participation and self-rated health are both heritable (around 50% of the
      variance of both phenotypes is explained by genetic factors). The genetic factors
      influencing exercise participation and self-rated health partially overlap (r =
      0.36) and this overlap fully explains their phenotypic correlation. We conclude
      that the association between exercise and self-rated health can be explained by
      genes predisposing to both exercise participation and self-rated health. These
      genes may directly influence both phenotypes (pleiotropy). Alternatively, genes
      that affect exercise or self-rated health may indirectly influence the other
      phenotype through a causal relationship. We propose that identification of the
      genes that cause differences in exercise behavior will help resolve the issue of
      causality.

PMID- 17195051
TI  - Temporal trends of esophageal cancer during 1995-2004 in Nanao Island, an
      extremely high-risk area in China.
AB  - The purpose of our study was to investigate the temporal malignant tumor
      incidence rates among the 70,000 residents at the relatively isolated Nanao
      Island in South China Sea. The data on all malignant tumor cases from Nanao
      Cancer Registry during 1995-2004 were coded, computerized, and analyzed using the
      software SPSS10.0. The tumor incident cases, crude incident rate, age
      standardized incidence rate, their sex distribution and temporal trend were
      assessed. A total of 1450 new cancer cases (990 males and 460 females) were
      identified. The annual average age-standardized incidence rate (ASR) of malignant
      tumors was 208.18/100,000. The age-standardized incidence rate of the ten leading
      cancers in both sexes combined per 100,000 population were 74.47 for esophageal
      cancer (EC), 34.81 for cardiac cancer (CC), 25.66 for liver cancer, 26.01 for
      lung cancer, 18.52 for stomach cancer, 4.45 for nasopharyngeal cancer, 3.91 for
      breast cancer, 2.53 for colon/rectum cancer, 2.45 for bladder cancer and 1.92 for
      pancreatic cancer. These ten types of cancers make up to 93% of all cancer cases,
      with EC and CC being the most prevalent and making up 52% of the total cases. The
      incidence rates of esophagus, liver, lung, breast, nasopharyngeal, and
      colon/rectum cancers showed increasing trends during the period from 1995 to 2004
      in Nanao Island. Astounding the EC ASR were 72-150/100,000 among male and 26
      64/100,000 among female in Nanao Island during 1995-2004. The EC incidence rate
      in Nanao population is among the highest across the world, which suggests that
      there are potential genetic and/or environmental factors affecting this
      particular population.

PMID- 17195052
TI  - Meiotic behaviour of a new complex X-Y-autosome translocation and amplified
      heterochromatin in Jumnos ruckeri (Saunders) (Coleoptera, Scarabaeidae,
      Cetoniinae).
AB  - Species belonging to the Cetoniinae subfamily studied so far possess 20
      chromosomes, including a small X and a punctiform Y: 20,Xyp in the males. In a
      series of species from the Goliathini tribe under study we found a very unusual
      karyotype, with 12 autosomes and large sex chromosomes (14,neoXY) in Jumnos
      ruckieri from Thailand. Applying various techniques including pachytene bivalent
      spreading, we showed that 40% (mitotic and meiotic prophases) to 60% (metaphases)
      of the karyotype length was composed of heterochromatin. Both sex chromosomes
      were NOR carriers. At pachynema they underwent a complete synapsis of their
      distal regions, indicating their autosomal origin. At contrast, their very uneven
      central regions remained separated, but associated with nucleolus material. This
      association persisted until diakinesis, forming a pseudo-chiasma between the neoX
      and the neoY, which were always in end-to-end association. Compared to free
      autosomes the autosomal parts of the neo-sex chromosomes had a significant lack
      of interstitial chiasmata, indicating a possible lack of recombination at their
      proximal regions. As in the cases of X-autosome translocations in mammals,
      autosomal and gonosomal parts of the neo-sex chromosomes were insulated by
      heterochromatin, which may be a necessary condition to avoid deleterious position
      effects, whatever the mechanisms of gene dosage compensation.

PMID- 17195053
TI  - Evolution of the karyotype and sex chromosome systems in basal clades of
      araneomorph spiders (Araneae: Araneomorphae).
AB  - Concepts of spider karyotype evolution are based mostly on advanced and most
      diversified clade, the entelegyne lineage of araneomorph spiders. Hence the
      typical spider karyotype is supposed to consist exclusively of acrocentric
      chromosomes including the multiple X chromosomes. However, our data show
      considerable diversity of chromosome morphology and sex chromosome systems in
      basal clades of araneomorphs. Karyotypes of basal araneomorphs consist of
      holocentric (superfamily Dysderoidea) or normal chromosomes with localized
      centromere. In males of basal araneomorphs the prophase of first meiotic division
      includes a long diffuse stage. Multiple X chromosomes are less common in basal
      clades. The sex chromosome system of many families includes a Y chromosome or
      nucleolus organizer region that occurs rarely in the entelegyne spiders. A
      derived X(1)X(2)Y system with an achiasmatic sex-chromosome pairing during
      meiosis was found in the families Drymusidae, Hypochilidae, Filistatidae,
      Sicariidae, and Pholcidae. This suggests a monophyletic origin of the families.
      In some lineages the X(1)X(2)Y system converted into an X0 system, as found in
      some pholcids, or into an XY system, which is typical for the family Diguetidae.
      The remarkable karyotype and sex chromosome system diversity allows us to
      distinguish four evolutionary lineages of basal araneomorphs and hypothesize
      about the ancestral karyotype of araneomorphs.

PMID- 17195054
TI  - Ribosomal DNA locus evolution in Nemesia: transposition rather than structural
      rearrangement as the key mechanism?
AB  - We investigated chromosome evolution in Nemesia using fluorescent in-situ
      hybridization (FISH) to identify the locations of 5S and 45S (18-26S) ribosomal
      genes. Although there was conservation between Nemesia species in chromosome
      number, size and centromere position, there was large variation in both number
      and position of ribosomal genes in different Nemesia species (21 different
      arrangements of 45S and 5S rRNA genes were observed in the 29 Nemesia taxa
      studied). Nemesia species contained between one and three pairs of 5S arrays and
      between two and four pairs of 45S arrays. These were either sub-terminally or
      interstitially located and 45S and 5S arrays were often located on the same
      chromosome pair. Comparison of the positions of rDNA arrays with meiotic
      chromosome behaviour in interspecific hybrids of Nemesia suggests that some of
      the changes in the positions of rDNA have not affected the surrounding chromosome
      regions, indicating that rDNA has changed position by transposition. Chromosome
      evolution is frequently thought to occur via structural rearrangements such as
      inversions and translocations. We suggest that, in Nemesia, transposition of rDNA
      genes may be equally if not more important in chromosome evolution.

PMID- 17195055
TI  - Effects of brimonidine ingestion on cardiovascular responses and renal function
      in conscious dogs.
AB  - The effects of brimonidine, an alpha(2)-adrenoceptor agonist, on blood pressure,
      heart rate, respiratory rate, renal function and some blood parameters were
      investigated in 10 dogs. Dogs were divided into two groups, low dose (LD; 0.2
      mg/kg) and high dose (HD; 0.5 mg/kg) of brimonidine given orally. The alpha(2)
      adrenergic antagonist yohimbine hydrochloride was injected to dogs at a dose of
      0.1 mg/kg in both groups at the fifth hour after brimonidine administration. The
      results demonstrated that after administration of brimonidine, mean arterial
      blood pressure decreased dramatically at 2 h by 23% and 20% in LD and HD groups,
      respectively. Heart rate was decreased in a similar manner and both remained low
      at 5 h after brimonidine administration. Respiratory rate was decreased by 50%,
      while the electrocardiogram showed prolongation of the PR interval. Glomerular
      filtration rate (GFR) and effective renal blood flow were reduced when measured
      at 4 h after brimonidine ingestion in both groups, but the effect was more
      pronounced in the LD group. Brimonidine caused natriuresis and kaliuresis in both
      LD and HD groups. The packed cell volume was decreased and hyperglycaemia was
      detected. Most of the effects can be reversed completely after administration of
      yohimbine. However, yohimbine can restore GFR only partially. These data suggest
      that brimonidine caused cardiovascular and respiratory depression. The adverse
      effects of this drug can be antagonized by yohimbine, suggesting that these
      effects were mediated via the alpha(2)-adrenoceptor.

PMID- 17195056
TI  - Comparative histomorphological study of heart in healthy and ascites broiler
      chickens in Shahrekord district, Iran.

PMID- 17195057
TI  - Quantitative genetics of speciation: additive and non-additive genetic
      differentiation between Drosophila madeirensis and Drosophila subobscura.
AB  - The role of dominance and epistasis in population divergence has been an issue of
      much debate ever since the neoDarwinian synthesis. One of the best ways to
      dissect the several genetic components affecting the genetic architecture of
      populations is line cross analysis. Here we present a study comparing generation
      means of several life history-traits in two closely related Drosophila species:
      Drosophila subobscura, D. madeirensis as well as their F1 and F2 hybrids. This
      study aims to determine the relative contributions of additive and non-additive
      genetic parameters to the differentiation of life-history traits between these
      two species. The results indicate that both negative dominance and epistatic
      effects are very important in the differentiation of most traits. We end with
      considerations about the relevance of these findings for the understanding of the
      role of non-additive effects in speciation.

PMID- 17195058
TI  - Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect
      on mushroom tyrosinase.
AB  - A novel tyrosinase inhibitor, an arbutin derivative having undecylenic acid at
      the 6-position of its glucose moiety, was enzymatically synthesized. Its
      inhibitory activity was studied in vitro by using catechol and phenol as
      substrates. The IC(50) value of the arbutin ester on tyrosinase using catechol (4
      x 10(-4) M) was 1% of that when arbutin (4 x 10(-2) M) was used. Using phenol,
      IC(50) of the arbutin ester (3 x 10(-4) M) as substrate was 10% of that of
      arbutin (3 x 10(-3) M). These results suggest that the arbutin ester inhibits the
      latter part of the tyrosinase reaction, which consists of hydroxylation and
      oxidation.

PMID- 17195059
TI  - Application of gene-shuffling for the rapid generation of novel [FeFe]
      hydrogenase libraries.
AB  - A gene-shuffling technique was identified, optimized and used to generate diverse
      libraries of recombinant [FeFe]-hydrogenases. Six native [FeFe]-hydrogenase genes
      from species of Clostridia were first cloned and separately expressed in
      Escherichia coli concomitantly with the assembly proteins required for [FeFe]
      hydrogenase maturation. All enzymes, with the exception of C. thermocellum HydA,
      exhibited significant activity when expressed. Single-stranded DNA fragments from
      genes encoding the two most active [FeFe]-hydrogenases were used to optimize a
      gene-shuffling protocol and generate recombinant enzyme libraries. Random
      sampling demonstrates that several shuffled products are active. This represents
      the first successful application of gene-shuffling using hydrogenases. Moreover,
      we demonstrate that a single set of [FeFe]-hydrogenase maturation proteins is
      sufficient for the heterologous assembly of the bioinorganic active site of
      several native and shuffled [FeFe]-hydrogenases.

PMID- 17195060
TI  - [Liver resection and transplantation for hepatic tumors].
AB  - Hepatic surgery has made substantial advances in the last two decades due to
      technical developments and improvements in perioperative management. This has
      reduced surgery dependent mortality to less than 5%, and provides the possibility
      of carrying out more substantial hepatic resections and to interpret the
      indications more liberally, also for tumours localized unfavorably. A widely
      standardized surgical technique as well as new possibilities for organ
      conservation and, in particular, immunosuppression mean that given suitable
      indications, liver transplantation is today regarded as a routine procedure for
      the treatment of hepatocellular carcinoma. This work provides an overview of the
      current status of surgical therapy for the most frequent, benign liver tumours,
      as well as for hepatocellular and cholangiocellular carcinoma.

PMID- 17195061
TI  - [Nuclear medical diagnostics for liver tumors].
AB  - Standard nuclear medical procedures, such as functional, blood-pool and colloid
      scintigraphy, play a minor role in the routine workup of liver tumors. However,
      these techniques are capable of assessing specific organ functions and frequently
      allow the diagnosis of unclear liver lesions. The sensitivity of scintigraphic
      procedures can be increased using tomographic imaging (SPECT), the specificity
      with the introduction of hybrid scanners such as SPECT/CT. Whole body positron
      emission tomography with 18F-fluoro-deoxy-glucose (FDG) in combination with CT
      scanning (PET/CT) represents one of the most sensitive imaging modalities for the
      detection of hepatic metastases and extrahepatic tumor manifestations. For the
      staging and follow-up of colorectal cancer, FDG-PET/CT represents a standard
      imaging modality. Metastases from neuroendocrine tumors can be detected using PET
      and specific tracers such as [68Ga]DOTATOC and [18F]DOPA. Molecular imaging with
      PET allows the quantification of metabolic processes which can be used for the
      assessment of an early response to treatment.

PMID- 17195062
TI  - Soluble thrombomodulin as a predictor of type 2 diabetes: results from the
      MONICA/KORA Augsburg case-cohort study, 1984-1998.
AB  - AIMS/HYPOTHESIS: Previous studies have shown an inverse association between
      soluble thrombomodulin (sTM) and incident CHD, but there is a lack of data on the
      association between sTM and type 2 diabetes. Since CHD and type 2 diabetes share
      many risk factors, the aim of this study was to assess whether elevated sTM
      levels are associated with a lower incidence of type 2 diabetes. MATERIALS AND
      METHODS: A case-cohort study was performed in initially healthy middle-aged men
      and women based on data from the Monitoring of Trends and Determinants in
      Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg
      (MONICA/KORA) studies conducted between 1984 and 1998. Levels of sTM were
      measured with an ELISA in serum samples from 138 men and 86 women who developed
      type 2 diabetes during follow-up (cases) and 534 men and 446 women who did not
      develop type 2 diabetes (non-cases). RESULTS: An inverse association was found
      between sTM and type 2 diabetes risk after multivariable adjustment for diabetes
      risk factors, including several other markers of inflammation and endothelial
      dysfunction. Markers of inflammation and endothelial dysfunction were
      particularly strong confounders of the observed association. In the fully
      adjusted model, a 1 SD increase in sTM was associated with a 27% decrease in the
      risk of type 2 diabetes (hazard ratio=0.73, 95% CI 0.58-0.91) in the total study
      population. We did not observe significant risk differences between men and
      women. CONCLUSIONS/INTERPRETATION: These data suggest that, in initially healthy
      middle-aged men and women, levels of sTM are inversely associated with the risk
      of type 2 diabetes.

PMID- 17195064
TI  - Hysterical paralysis.
AB  - Hysterical paralysis is an uncommon type of conversion disorder. It can be
      difficult to diagnose. In cases in which symptoms are difficult to explain
      neuroanatomically or are functionally inconsistent, hysteria should enter into
      the differential diagnosis. We report a case of hysterical paralysis that had
      rapid improvement using physical therapy and antidepressant therapy.

PMID- 17195065
TI  - Adaptation of the RAQoL for use in Australia.
AB  - Quality of life is an important patient-reported outcome of rheumatoid arthritis
      (RA) in addition to structural and functional outcomes. The RAQoL (Rheumatoid
      Arthritis Quality of Life questionnaire) was developed in the UK and the
      Netherlands as a disease-specific tool. It was adapted for use in the Australian
      social context and the reliability and validity was tested. A lay panel assessed
      the UK version and adapted the wording for use within Australia. Reliability and
      validity were assessed by a postal survey of the RAQoL and comparator
      questionnaires to 100 patients with RA. The RAQoL was easily adapted into
      Australian-English. Test-retest reliability was high with a Spearman rank
      correlation coefficient of 0.93. RAQoL scores correlated well with patient
      perceived disease activity and severity--indicating good validity. The Australian
      version of the RAQoL is a valid and reliable tool for the assessment of quality
      of life. It is practical, easy to administer and has good potential for use in
      clinical settings and trials in Australia.

PMID- 17195063
TI  - Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin
      hypersensitivity.
AB  - AIMS/HYPOTHESIS: Insulin controls glucose metabolism via multiple signalling
      pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway in muscle
      and adipose tissue. The protein/lipid phosphatase Pten (phosphatase and tensin
      homologue deleted on chromosome 10) attenuates PI3K signalling by
      dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate generated by PI3K.
      The current study was aimed at investigating the effect of haploinsufficiency for
      Pten on insulin-stimulated glucose uptake. MATERIALS AND METHODS: Insulin
      sensitivity in Pten heterozygous (Pten(+/-)) mice was investigated in i.p.
      insulin challenge and glucose tolerance tests. Glucose uptake was monitored in
      vitro in primary cultures of myocytes from Pten(+/-) mice, and in vivo by
      positron emission tomography. The phosphorylation status of protein kinase B
      (PKB/Akt), a downstream signalling protein in the PI3K pathway, and glycogen
      synthase kinase 3beta (GSK3beta), a substrate of PKB/Akt, was determined by
      western immunoblotting. RESULTS: Following i.p. insulin challenge, blood glucose
      levels in Pten(+/-) mice remained depressed for up to 120 min, whereas glucose
      levels in wild-type mice began to recover after approximately 30 min. After
      glucose challenge, blood glucose returned to normal about twice as rapidly in
      Pten(+/-) mice. Enhanced glucose uptake was observed both in Pten(+/-) myocytes
      and in skeletal muscle of Pten(+/-) mice by PET. PKB and GSK3beta phosphorylation
      was enhanced and prolonged in Pten(+/-) myocytes. CONCLUSIONS/INTERPRETATION:
      Pten is a key negative regulator of insulin-stimulated glucose uptake in vitro
      and in vivo. The partial reduction of Pten due to Pten haploinsufficiency is
      enough to elicit enhanced insulin sensitivity and glucose tolerance in Pten(+/-)
      mice.

PMID- 17195066
TI  - Late onset systemic lupus erythematosus: no substantial differences using
      different cut-off ages.
AB  - To compare the clinical, laboratory and immunological features of a group of
      Caucasian systemic lupus erythematosus (SLE) patients in relation to age at
      disease onset. Three groups of patients with different ages at disease onset were
      analysed and compared: group A (30 patients, >or=65 years); group B (62 patients,
      50-64 years) and group C (163 patients, <50 years). All patients were regularly
      followed-up for a mean period of 6.5 years. Female predominance was reduced in
      groups A and B. Time-lapse between disease onset and diagnosis was longer in
      group A and B. There were no statistically significant differences in clinical
      features. The only relevant difference was observed in peripheral nervous system
      (PNS) involvement, more frequent in group A. Anti-dsDNA and RF were more frequent
      in group A. Complement levels were reduced more frequently in group C. No
      differences were observed in disease activity scores, while SLICC/ACR score was
      higher in group A. In Caucasian SLE patients, age at disease onset is not
      associated with differences in clinical features apart from a more frequent PNS
      involvement in elderly patients. In the same group, the organ damage seems to
      develop more rapidly mostly due to higher susceptibility to jatrogenic side
      effects.

PMID- 17195067
TI  - WP760, a melanoma selective drug.
AB  - PURPOSE: Our goal was to perform studies on the specificity and antimelanoma
      mechanism of a novel bis-anthracycline, WP760. WP760 initially identified in the
      NCI 160 screen as anti-melanoma. METHODS: The methyl thiazolyl tetrazolium
      reduction (MTT) assay was used to test tumor cell growth inhibition; confocal
      microscopy to view WP760 intracellular distribution; flow cytometry for cell
      cycle arrest and apoptosis; and Western blotting was employed to identify and
      compare quantities and kinetics of cell growth related molecule levels. RESULTS:
      WP760 induced G(2)/M-phase cell-cycle arrest and apoptosis in melanoma cell lines
      and short-term melanoma explants established from clinical specimens in a time
      and concentration dependent manner at nM concentrations. In contrast, effects on
      fibroblasts and A549 lung cancer cells required higher concentrations, suggesting
      that WP760 possesses selectivity for melanoma. Molecular studies indicated that
      WP760 induced p53 stabilization, checkpoint kinase 2 and p27(Kip1) protein
      upregulation, and activation of caspase-3. Endogenous nitric oxide (NO)
      production has been implicated in the chemoresistance of melanoma; WP760 caused
      inhibition of the inducible nitric oxide synthase (iNOS) protein as well as
      inhibition of phosphorylation of ERK, known to drive the iNOS pathway. Based on
      WP760 localization into mitochondria, and caspase-3 inhibitor block the killing
      of WP760, the intrinsic pathway of apoptosis appears to have been activated.
      CONCLUSIONS: Our results indicate that WP760 affects a critical and unique set of
      growth regulatory effects in melanoma, and is a promising candidate for further
      preclinical studies.

PMID- 17195068
TI  - A limited sampling strategy to estimate individual pharmacokinetic parameters of
      methotrexate in children with acute lymphoblastic leukemia.
AB  - PURPOSE: The objectives of this study were to characterize the population
      pharmacokinetics of MTX in patients with acute lymphoblastic leukemia (ALL) with
      ages ranging from 2 to 16 years and to propose a limited sampling strategy to
      estimate individual pharmacokinetic parameters. METHODS: Seventy-nine children
      were enrolled in this study; they received 1-4 courses of chemotherapy. MTX was
      administered at a dose of 5 g/m2. MTX population parameters were estimated from
      61 patients (231 courses; age range: 2-16 years). The data were analyzed by
      nonlinear mixed-effect modeling with use of a two-compartment structural model.
      The interoccasion variability was taken into account in the model. Eighteen
      additional patients (70 courses) were used to evaluate the predictive
      performances of the Bayesian approach and to devise a limited sampling strategy.
      RESULTS: The following population parameters were obtained: total clearance (CL)
      = 8.8 l/h (inter-individual variability: 43%), initial volume of distribution
      (V1) = 17.3 l (48%), k12 = 0.0225 h(-1) (41%), and k21 = 0.0629 h(-1) (24%). The
      inter-individual variability in the initial volume of distribution was partially
      explained by the fact that this parameter was weight-dependent. Intercourse
      variability was limited, with a mean variation of 13.2%. The protocol involving
      two sampling times, 24 and 48 h after the beginning of infusion, allows precise
      and accurate determination of individual pharmacokinetic parameters and
      consequently, it was possible to predict the time at which the MTX concentration
      reached the predicted threshold (0.2 microM) below which the administration of
      folinic acid could be stopped. CONCLUSION: The results of this study combine the
      relationships between the pharmacokinetic parameters of MTX and patient
      covariates that may be useful for dose adjustment, with a convenient sampling
      procedure that may aid in optimizing pediatric patient care.

PMID- 17195069
TI  - Drug related problems and off-label drug treatment in children as seen at a drug
      information centre.
AB  - The aim of this work was to analyse the characteristics of Questions and Answers
      (Q&As) at a drug information centre (DIC) regarding drug related problems and off
      label drug treatment in children. All questions concerning children 15 years or
      younger at a DIC in Stockholm, Sweden during the years 1995-2004 were analysed
      with respect to the main drug related problem, drug/s and drug group/s, whether
      the drugs were licensed or not, pediatric labelling of the drug/s and age and sex
      of the patient. Q&As were classified as whether or not they included evaluated
      literature information, adding to the labelling of the drugs. We identified 249
      Q&As concerning pediatric drug treatment. Each question addressed an average of
      1.5 drugs. More than two-thirds of the Q&As concerned adverse drug reactions and
      pediatric drug choice or dosing. Every second question was classified as off
      label, psychotropic drugs being the most common. In half of all off-label Q&As,
      pediatric documentation on drug efficacy and safety outside the Swedish catalogue
      of medical products was found. Most Q&As concerned newborns and infants. However,
      the off-label proportion among questions was highest in adolescence as well as
      the evaluated literature information, adding to the labelling of the drugs. It
      was thus found that off-label drug treatment is common among pediatric questions
      at a DIC. This service can provide additional literature based information
      contributing to a safer use of drugs in children. There is still, however, a
      substantial need for clinical documentation of drug use in children.

PMID- 17195070
TI  - Pulmonary embolism--a rare complication of Schimke immunoosseous dysplasia.

PMID- 17195071
TI  - [Intraosseous puncture in preclinical emergency medicine. Ten years experience in
      air rescue service].
AB  - INTRODUCTION: The intraosseous puncture (IO) is a fast and safe alternative to
      the puncture of peripheral veins in emergency situations in children < or =6
      years of age. The purpose of this paper is to summarize 10 years of experience on
      the prehospital use of the IO method by the Helicopter Emergency Medical Service
      (HEMS) "Christoph 22", Ulm. MATERIALS AND METHODS: This was a retrospective study
      from 1 January 1996 to 31 December 2005. RESULTS: Out of a total of 9,549
      missions, the proportion of children was 11.1%. In 27 children (4.2% of the
      children < or =6 years of age) an IO puncture was performed. Patients of the IO
      group were younger (1.0 vs. 3.7 years of age; p<0.001) and showed a higher degree
      of injury severity (NACA 6 vs. 4; p<0.001) compared to the total children group.
      In all children of the IO group (100%), the intraosseous puncture was the method
      of first choice to obtain access to the vascular system by the HEMS team. In
      96.4% of these cases (26/27), the first IO puncture attempt was successful - in
      one child, a second puncture attempt was necessary. A standardized puncture
      technique was performed using the proximal tibia. The time required for
      successful placement of the IO infusion line was 60 s or less in all cases. In
      37% of the cases (10/27) the IO infusion line was used for induction of general
      anaesthesia; dosage and onset of administered drugs were described as being
      equivalent to a peripheral infusion line. In all cases, the IO needle was
      replaced in-hospital within 2 h by a central or peripheral iv line. No
      complications were observed. CONCLUSIONS: The IO infusion technique is a simple,
      fast and safe alternative method for emergency access to the vascular system in
      children < or =6 years of age in the prehospital setting.

PMID- 17195072
TI  - FDG-PET in the clinical management of carcinoma of unknown primary with
      metastatic cervical lymphadenopathy: shifting gears from detecting the primary to
      planning therapeutic strategies.

PMID- 17195073
TI  - Reproducibility of 5-HT2A receptor measurements and sample size estimations with
      [18F]altanserin PET using a bolus/infusion approach.
AB  - PURPOSE: To determine the reproducibility of measurements of brain 5-HT2A
      receptors with an [18F]altanserin PET bolus/infusion approach. Further, to
      estimate the sample size needed to detect regional differences between two groups
      and, finally, to evaluate how partial volume correction affects reproducibility
      and the required sample size. METHODS: For assessment of the variability, six
      subjects were investigated with [18F]altanserin PET twice, at an interval of less
      than 2 weeks. The sample size required to detect a 20% difference was estimated
      from [18F]altanserin PET studies in 84 healthy subjects. Regions of interest were
      automatically delineated on co-registered MR and PET images. RESULTS: In cortical
      brain regions with a high density of 5-HT2A receptors, the outcome parameter
      (binding potential, BP1) showed high reproducibility, with a median difference
      between the two group measurements of 6% (range 5-12%), whereas in regions with a
      low receptor density, BP1 reproducibility was lower, with a median difference of
      17% (range 11-39%). Partial volume correction reduced the variability in the
      sample considerably. The sample size required to detect a 20% difference in brain
      regions with high receptor density is approximately 27, whereas for low receptor
      binding regions the required sample size is substantially higher. CONCLUSION:
      This study demonstrates that [18F]altanserin PET with a bolus/infusion design has
      very low variability, particularly in larger brain regions with high 5-HT2A
      receptor density. Moreover, partial volume correction considerably reduces the
      sample size required to detect regional changes between groups.

PMID- 17195074
TI  - PET imaging with [18F]3'-deoxy-3'-fluorothymidine for prediction of response to
      neoadjuvant treatment in patients with rectal cancer.
AB  - PURPOSE: Positron emission tomography (PET) using 18F-labelled 3'-deoxy-3'
      fluorothymidine (FLT) was assessed for therapy monitoring in patients with rectal
      cancer undergoing neoadjuvant chemoradiotherapy. METHODS: Ten patients with
      locally advanced rectal cancer were included and underwent long-course
      preoperative chemoradiotherapy (total dose 45 Gy, 1.8 Gy/day, concomitant 250
      mg/m2 5-fluorouracil) followed by surgery. FLT-PET was performed prior to
      chemoradiotherapy, 2 weeks after initiation of chemoradiotherapy and
      preoperatively (3-4 weeks post chemoradiotherapy). FLT uptake was correlated with
      histopathological tumour regression and changes in T stage. RESULTS: Mean tumour
      FLT uptake was 4.2+/-1.0 SUV before therapy and decreased significantly to 2.9+/
      0.6 SUV 14 days after initiation of chemoradiotherapy (-28.6%+/-10.7%, p=0.005).
      The preoperative scan showed a further decrease to 1.9+/-0.4 SUV (-54.7%+/-7.6%,
      p=0.005). However, the degree of change in FLT uptake 2 weeks after initiation
      and after completion of neoadjuvant therapy did not correlate with
      histopathological tumour regression. CONCLUSION: FLT-PET did not seem to be a
      promising method for assessment of tumour response in the studied
      chemoradiotherapy regimen in patients with rectal cancer.

PMID- 17195075
TI  - Fluorine-18 fluorodeoxyglucose PET in the preoperative staging of colorectal
      cancer.
AB  - INTRODUCTION: In patients with colorectal cancer (CC), preoperative evaluation
      and staging should focus on techniques that might alter the preoperative or
      intraoperative surgical plan. Conventional imaging methods (CT, MRI) have low
      accuracy for identifying the depth of tumour infiltration and have limited
      ability to detect regional lymph node involvement. The aim of this study was to
      evaluate the utility of FDG-PET in the initial staging of patients with CC in
      comparison with conventional staging methods and to determine its impact on
      therapeutic management. METHODS: One hundred and four patients with a diagnosis
      of CC (53 males and 51 females; mean age 66.76+/-12.36 years), selected
      prospectively, were studied for staging using a standard procedure (CT) and FDG
      PET. When possible, the reference method was histology. RESULTS: In 14 patients,
      surgery was contraindicated by FDG-PET owing to the extent of disease (only 6/14
      suspected by CT). FDG-PET revealed four synchronous tumours. For N staging, both
      procedures showed a relatively high specificity but a low diagnostic accuracy
      (PET 56%, CT 60%) and sensitivity (PET 21%, CT 25%). For M assessment, diagnostic
      accuracy was 92% for FDG-PET and 87% for CT. FDG-PET results led to modification
      of the therapy approach in 50% of patients with unresectable disease. FDG-PET
      findings were important, revealing unknown disease in 19.2%, changing the staging
      in 13.46% and modifying the scope of surgery in 11.54% (with a change in the
      therapeutic approach in 17.85% of those patients with rectal cancer). CONCLUSION:
      Compared with conventional techniques, FDG-PET appears to be useful in pre
      surgical staging of CC, revealing unsuspected disease and impacting on the
      treatment approach.

PMID- 17195077
TI  - Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on
      implications for chronic infections and tumor evasion.
AB  - Recent clinical data support ideas of Programmed death receptor-ligand 1 (PD-L1;
      also called B7-H1, CD274) playing an important role in immune evasion of tumor
      cells. Expression of PD-L1 on tumors strongly correlates with the survival of
      cancer patients. PD-L1 on tumors interacts with the co-inhibitory molecule
      Programmed death receptor-1 (PD-1, CD279) on T cells mediating decreased TCR
      mediated proliferation and cytokine production. In animal tumor models, blockade
      of PD-L1/PD-1 interactions resulted in an improved tumor control. In addition,
      exhausted T cells during chronic viral infections could be revived by PD-L1
      blockade. Thus, targeting PD-L1/PD-1 interactions might improve the efficacy of
      adoptive cell therapies (ACT) of chronic infections as well as cancers. Obstacles
      for a general blockade of PD-L1 might be its role in mediating peripheral
      tolerance. This review discusses the currently available data concerning the role
      of PD-L1 in tumor immune evasion and envisions possibilities for implementation
      into ACT for cancer patients.

PMID- 17195076
TI  - The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1
      in colon carcinoma.
AB  - The epithelial mucin MUC1 is a high molecular weight membrane glycoprotein
      frequently overexpressed and aberrantly glycosylated in adenocarcinoma. Mucins
      normally contain high amounts of O-linked carbohydrate structures that may
      influence immune reactions to this antigen. During malignant transformation,
      certain glyco-epitopes of MUC1, such as Tn-antigen, TF-antigen and their
      sialylated forms become exposed. The role of these glycan structures in tumor
      biology is unknown, but their presence is known to correlate with poor prognosis
      in several adenocarcinomas. We analyzed the potency of MUC1 containing Tn
      antigens (MUC1-Tn) to target C-type lectins that function as carbohydrate
      recognition and uptake molecules on dendritic cells (DC). We identified the
      macrophage galactose type C-type lectin (MGL), expressed by both DC and
      macrophages, as the receptor for recognition and binding of MUC1-Tn. To validate
      the occurrence of MGL-MUC1 interactions in situ, we studied the binding of MGL to
      MUC1 in primary colon carcinoma tissue. Isolation of MUC1 out of colon carcinoma
      tissue showed strong binding activity to MGL. Interestingly, MGL binding to MUC1
      was highly correlated to binding by the lectin Helix pomatia agglutinin (HPA),
      which is associated with poor prognosis in colorectal cancer. The detection of
      MGL positive cells in situ at the tumor site together with the modified
      glycosylation status of MUC1 to target MGL on DC suggests that MGL positive
      antigen presenting cells may play a role in tumor progression.

PMID- 17195078
TI  - CD8(+) T lymphocytes isolated from renal cancer patients recognize tumour cells
      through an HLA- and TCR/CD3-independent pathway.
AB  - PURPOSE: The aim of this study was to characterize the immune response of
      patients affected by renal cell carcinoma (RCC). METHODS: Long-term RCC lines
      were established by retroviral-mediated transfer of the large T-antigen of SV40
      into fresh carcinoma cells. Reactive T cell effectors were generated by iterative
      stimulations of patients' PBMC with autologous tumour cells. RESULTS: This
      protocol led to the induction of CD8(+) T cell clones reactive against the
      autologous tumour, but not against NK-sensitive cell lines. However, some of
      these effectors recognize normal renal cells, allogeneic renal carcinoma cell
      lines and colon and non-small cell lung carcinomas but not melanomas and
      lymphoblastoid lines, without evidence of shared classical HLA class I (HLA-I)
      molecules. Further characterization performed on the CD8(+) TCR alpha/beta(+)
      clone, CTL30, demonstrated that neither expression of CD1, HLA-Ia nor HLA-Ib,
      correlated with the T cells' recognition. Moreover, beta2m expression by target
      cells was not required to achieve interaction of tumour-effector cells. In
      agreement with this observation, the lytic activity of CTL30 was not inhibited by
      anti-HLA-I Ab, and antigen expression was not affected by inhibitors of antigen
      processing. Lytic activity of CTL30, while partially inhibited by anti-NKG2D,
      could not be abolished by anti-CD3 Abs. Moreover, growth and expansion of CTL30
      was sustained only by T cell interaction with antigen-expressing tumour cells;
      unspecific mitogenic stimuli, such as anti-CD3 and PHA, did not allow T cell
      expansion. These results demonstrated the existence of an alpha/beta T cell
      population, recognizing epithelial tumour cells through an HLA-unrestricted, CD3
      independent mechanism.

PMID- 17195081
TI  - Effect of tobacco smoking on advancement flap repair of complex anal fistulas.
AB  - PURPOSE: Options for the management of complex anal fistulas include fistulotomy,
      setons, fibrin sealant, and advancement flaps. This study was performed to
      evaluate our results with advancement flap repair of anal fistulas and to
      identify factors associated with failure. METHODS: A retrospective analysis was
      performed for all patients treated with an anal fistula between June 2000 and May
      2003. Data collected included age, gender, fistula anatomy and etiology, previous
      repairs, comorbidities, smoking history, procedure performed, and fistula
      recurrence. RESULTS: There were 95 patients (43 males and 52 females) with a mean
      age of 42 years. Transsphincteric fistulas were present in 51 patients and 44
      females had rectovaginal fistulas. A mucosal flap repair was performed for 68
      patients and 27 patients had an anodermal flap repair. The median length of
      follow-up was ten months. The fistula recurred in 31 patients (32.6 percent).
      Subset analysis showed an association between a history of previous attempts at
      repair or tobacco smoking and an increased rate of fistula recurrence, but did
      not reveal any increased risk of recurrence for patients over age 40 years, for
      those with rectovaginal fistula, or for males. CONCLUSION: A history of previous
      attempts at repair of an anal fistula or tobacco smoking is associated with an
      increased risk of fistula recurrence; while age over 40 years, male gender, or a
      rectovaginal fistula are not.

PMID- 17195079
TI  - Dendritic cell based antitumor vaccination: impact of functional indoleamine 2,3
      dioxygenase expression.
AB  - BACKGROUND: Recent reports have demonstrated that the enzyme indoleamine 2,3
      dioxygenase (IDO) is upregulated in human dendritic cells (DCs) upon in vitro
      maturation. IDO is supposed to convey immunosuppressive effects by degrading the
      essential amino acid tryptophan, thereby downregulating T-cell functions. Hence,
      we evaluated IDO expression in DC preparations used for therapeutic DC
      vaccination and its in vivo effects. PATIENTS, METHODS AND RESULTS: IDO
      expression was detected by real-time-PCR in a series of human clinical grade DCs
      (n = 28) prior to vaccination of advanced melanoma patients (n = 11). These
      analyses revealed an intra- and interpersonal variation in IDO mRNA levels. IDO
      was strongly upregulated in human DCs on RNA and on protein level upon in vitro
      maturation by Interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF
      alpha), Interleukin-6 (IL-6) and Prostaglandin E2 (PGE2) over a time course of 24
      h. The enzymatic activity of induced IDO was demonstrated by measuring tryptophan
      degradation. Moreover, in biopsies obtained 24 h after application of the DC
      vaccine a prominent infiltrate of IDO-positive cells was observed by
      immunohistochemistry. The inflammatory infiltrate of these sites stained positive
      for the transcription factor Forkhead box P3 (FoxP3), suggesting an IDO-mediated
      induction of regulatory T-cells. All analysed melanoma patients (n = 11)
      receiving DC based immunotherapy exhibited rapid disease progression with a short
      overall survival due to advanced tumour stage. CONCLUSION: The presented
      observations suggest a potential clinical relevance of IDO expression in DC-based
      therapeutic vaccines via the attraction or induction of FoxP3(+) T-cells.

PMID- 17195082
TI  - Practice parameters for sigmoid diverticulitis.

PMID- 17195085
TI  - Laparoscopic resection in rectal cancer patients: outcome and cost-benefit
      analysis.
AB  - PURPOSE: This study was designed to evaluate the impact of laparoscopic rectal
      resection on short-term postoperative morbidity and costs. METHODS: A total of
      168 patients with rectal cancer were randomly assigned to laparoscopic (n = 83)
      or open (n = 85) resection. Outcome parameters were: postoperative morbidity,
      length of hospital stay, quality of life, long-term survival, and local
      recurrences. The mean follow-up period was 53.6 months. Cost-benefit analysis was
      based on hospital costs. RESULTS: Operative time was 53 minutes longer in the
      laparoscopic group (P < 0.0001). Postoperative morbidity rate was 28.9 percent in
      the laparoscopic vs. 40 percent in the open group (P = 0.18). The mean length of
      hospital stay was 10 (4.9) days in the laparoscopic group and 13.6 (10) days in
      the open group (P = 0.004). Local recurrence rate and five-year survival were
      similar in both groups; however, the limited number of patients does not allow
      firm conclusions. Quality of life was better in the laparoscopic group only in
      the first year after surgery (P < 0.0001). The additional charge in the
      laparoscopic group was $1,748 per patient randomized ($1,194 the result of
      surgical instruments and $554 the result of longer operative time). The saving in
      the laparoscopic group was $1,396 per patient randomized ($647 the result of
      shorter length of hospital stay and $749 the result of the lower cost of
      postoperative complications). The net balance resulted in $351 extra cost per
      patient randomly allocated to the laparoscopic group. CONCLUSIONS: Short-term
      postoperative morbidity was similar in the two groups. Laparoscopic resection
      reduced length of hospital stay, improved first-year quality of life, and
      slightly increased hospital costs.

PMID- 17195086
TI  - Goblet cell carcinoid tumors (adenocarcinoid) of the appendix.
AB  - PURPOSE: Goblet cell appendiceal carcinoids represent rare tumors that exhibit
      histologic features of both adenocarcinomas and neuroendocrine tumors. We present
      the long-term results of a series of 15 patients, focusing on clinical
      manifestations, diagnosis, and management. METHODS: Eight male and seven female
      patients (median age, 52.8 years) were included. Final diagnosis was confirmed by
      histology. Patients were evaluated clinically, biochemically, and radiologically
      every four months. Median follow-up was 30 months. RESULTS: The majority of
      patients (7/15) presented with symptoms compatible with acute appendicitis. Right
      hemicolectomy was performed in all except one, who subsequently developed
      metastases. Three patients had metastases at previous diagnosis. Plasma
      chromogranin-A was slightly elevated in two of them, while urinary 5-hydroxy
      indol-acetic acid was normal. (111)Indium-labeled octreotide scintigraphy was
      positive only in two of the four patients with metastases. Ki67 index was greater
      than 20 percent in all of them, while in only one with local tumor. Combination
      chemotherapy with either cisplatin plus etoposide or with 5-fluorouracil,
      cisplatin, and streptozotocin was administered to all patients with metastases
      resulting in temporary stabilization of disease. Twelve patients are alive, while
      three died of their disease 9, 13, and 14 months after diagnosis. CONCLUSIONS:
      The diagnostic value of chromogranin-A, urinary 5-hydroxy-indol-acetic acid, and
      (111)Indium-labeled octreotide scintigraphy seems to be limited in these tumors.
      Ki67 index appears to predict tumor behavior. Right hemicolectomy may reduce the
      risk of developing metastases. Chemotherapy may have efficacy in metastatic
      disease, however, more data are required to determine this and the optimal
      regimen.

PMID- 17195087
TI  - Cold-adapted enzymes from marine Antarctic microorganisms.
AB  - The Antarctic marine environment is characterized by challenging conditions for
      the survival of native microorganisms. Indeed, next to the temperature effect
      represented by the Arrhenius law, the viscosity of the medium, which is also
      significantly enhanced by low temperatures, contributes to slow down reaction
      rates. This review analyses the different challenges and focuses on a key element
      of life at low temperatures: cold-adapted enzymes. The molecular characteristics
      of these enzymes are discussed as well as the adaptation strategies which can be
      inferred from the comparison of their properties and three-dimensional structures
      with those of their mesophilic counterparts. As these enzymes display a high
      specific activity at low and moderate temperatures associated with a relatively
      high thermosensitivity, the interest in these properties is discussed with regard
      to their current and possible applications in biotechnology.

PMID- 17195088
TI  - Methylation and gene silencing of the Ras-related GTPase gene in lung and breast
      cancers.
AB  - BACKGROUND: RRAD, a small Ras-related GTPase, is highly expressed in human
      skeletal muscle, lung, and heart. Although loss of expression of RRAD in breast
      cancer cells has been reported and it may act as an oncogene, the mechanism of
      silencing is unknown. METHODS: We examined (1) mRNA expression of RRAD in lung
      and breast cancer cell lines using RT-PCR and (2) methylation status of lung and
      breast cancers. RESULTS: Loss of RRAD expression was found in 14 of 20 (70%)
      NSCLC cell lines, 11 of 11 (100%) SCLC cell lines, and 8 of 10 (80%) breast
      cancer cell lines; expression was not affected in normal bronchial and mammary
      epithelial cells. Treatment of 23 expression-negative cell lines with a
      demethylating agent restored expression in all cases. We developed a methylation
      specific assay from the analysis of bisulfite sequencing of the 5' region of RRAD
      in expression-negative and positive cell lines, which resulted in good
      concordance between methylation and expression. Primary lung and breast cancers
      showed hypermethylation in 89 of 214 (42%) and 39 of 63 (62%) cases,
      respectively. RRAD hypermethylation correlated with smoking history and poorer
      prognosis in lung adenocarcinomas. CONCLUSIONS: We conclude that epigenetic
      silencing of RRAD is a frequent event in lung and breast cancers, and analysis of
      it may provide novel opportunities for prognosis and therapy of these cancers.

PMID- 17195089
TI  - Histone deacetylase inhibitors enhance Ad5-TRAIL killing of TRAIL-resistant
      prostate tumor cells through increased caspase-2 activity.
AB  - Interest in TNF-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic
      has been high since its first description. Recently, the use of histone
      deacetylase inhibitors (HDACi) to treat cancer has progressed from the laboratory
      to the clinic, and the combination of HDACi and TRAIL is very powerful in killing
      human tumors. Using a panel of prostate tumor cell lines (ALVA-31, DU-145, and
      LNCaP) with varying TRAIL sensitivity, we examined their sensitization to a
      recombinant adenovirus encoding TRAIL (Ad5-TRAIL) by sodium butyrate and
      trichostatin A. HDACi treatment increased coxsackie-adenovirus receptor (CAR)
      expression, resulting in increased adenoviral infection, and increased TRAIL
      mediated killing. In TRAIL-resistant DU-145 cells, HDAC inhibition also decreased
      protein kinase casein kinase (PKCK) 2 activity, leading to caspase-2 activation.
      The importance of PKCK2 and caspase-2 in DU-145 sensitization was demonstrated
      with the PKCK-2-specific inhibitor, which enhanced Ad5-TRAIL-induced death, or
      the caspase-2-specific inhibitor, zVDVAD, which blocked Ad5-TRAIL-induced death.
      Thus, our data highlight the connection between HDAC inhibition of PKCK2 activity
      and tumor cell sensitivity to TRAIL-induced apoptosis. Specifically, HDAC
      inhibition leads to decreased PCKC2 activity, which is followed by caspase-2
      activation and partial cleavage of caspase-8 that sensitizes the tumor cell to
      TRAIL.

PMID- 17195090
TI  - Taxol induced apoptosis regulates amino acid transport in breast cancer cells.
AB  - A major outcome from Taxol treatment is induction of tumor cell apoptosis.
      However, metabolic responses to Taxol-induced apoptosis are poorly understood. In
      this study, we hypothesize that alterations in specific amino acid transporters
      may affect the Taxol-induced apoptosis in breast cancer cells. In this case, the
      activity of the given transporter may serve as a biomarker that could provide a
      biological assessment of response to drug treatment. We have examined the
      mechanisms responsible for Taxol-induced neutral amino acid uptake by breast
      cancer cells, such as MCF-7, BT474, MDAMB231 and T47D. The biochemical and
      molecular studies include: (1) growth-inhibition (MTT); (2) transport kinetics:
      (3) substrate-specific inhibition; (4) effect of thiol-modifying agents NEM and
      NPM; (5) gene expression of amino acid transporters; and (6) apoptotic assays.
      Our data show that Taxol treatment of MCF-7 cells induced a transient increase in
      Na(+)-dependent transport of the neutral amino acid transporter B0 at both gene
      and protein level. This increase was attenuated by blocking the transporter in
      the presence of high concentrations of the substrate amino acid. Other neutral
      amino acid transporters such as ATA2 (System A) and ASC were not altered. Amino
      acid starvation resulted in the expected up-regulation of System A (ATA2) gene,
      but not for B0 and ASC. B0 was significantly down regulated. Taxol treatment had
      no significant effect on the uptake of arginine and glutamate as measured by
      System y(+) and X(-) (GC) respectively. Tunel assays and FACS cell cycle analysis
      demonstrated that both Taxol- and doxorubicin-induced upregulation of B0
      transporter gene with accompanying increase in cell apoptosis, could be reversed
      partially by blocking the B0 transporter with high concentration of alanine,
      and/or by inhibiting the caspase pathway. Both Taxol and doxorubicin treatment
      caused a significant decrease in S-phase of the cell cycle. However, Taxol
      induced an increase primarily in the G2 fraction while doxorubicin caused
      increase in G1/G0 together with a small increase in G2. In summary, our study
      showed that Taxol induced apoptosis in several breast cancer cells results in
      activation of amino acid transporter System B0 at both gene and protein level.
      Similar response was observed with another chemotherapeutic agent Doxorubicin,
      suggesting that this increase is in response to apoptosis, and not only due to
      changes in cell cycle related events.

PMID- 17195091
TI  - Mitochondria are not required for death receptor-mediated cytosolic acidification
      during apoptosis.
AB  - In addition to cell shrinkage, membrane blebbing, DNA fragmentation and
      phosphatidylserine exposure, intracellular acidification represents a hallmark of
      apoptosis. Although the mechanisms underlying cytosolic acidification during
      apoptosis remained largely elusive, a pivotal role of mitochondria has been
      proposed. In order to investigate the involvement of mitochondria in cytosolic
      acidification during apoptosis, we blocked the mitochondrial death pathway by
      overexpression of Bcl-2 and subsequently activated the death receptor pathway by
      anti-CD95 or TRAIL or the mitochondrial pathway by staurosporine. We show that
      Bcl-2 but not caspase inhibition prevented staurosporine-induced intracellular
      acidification. Thus, intracellular acidification in mitochondrial apoptosis is a
      Bcl-2-inhibitable, but caspase-independent process. In contrast, Bcl-2 only
      slightly delayed, but did not prevent intracellular acidification upon triggering
      of death receptors. The Na(+)/H(+) exchanger NHE1 was partially degraded during
      apoptosis but only to a small extent and and at a delayed time point when
      cytosolic acidification was almost completed. We therefore conclude that
      cytosolic acidification is mitochondrially controlled in response to mitochondria
      dependent death stimuli, but requires additional caspase-dependent mechanisms
      during death receptor-mediated apoptosis.

PMID- 17195092
TI  - CD95 tyrosine phosphorylation is required for CD95 oligomerization.
AB  - Proapoptotic stimuli, such as CD95 ligand and hydrophobic bile acids induce an
      epidermal growth factor receptor (EGFR)-catalyzed tyrosine phosphorylation of
      CD95-death receptor in hepatocytes, as a prerequisite for CD95-translocation to
      the plasma membrane, formation of the death-inducing signalling complex and
      execution of apoptotic cell death. However, the molecular role played by CD95
      tyrosine phosphorylation remained unclear. The present study shows that CD95
      tyrosine phosphorylation is required for CD95-oligomerization. Fluorescence
      resonance energy transfer (FRET)-analysis in Huh7 hepatoma cells, which were
      cotransfected with CD95-YFP/CD95-CFP revealed that stimulation of these cells
      with CD95 ligand, proapoptotic bile acids or hyperosmolarity resulted within 30
      min in an intracellular FRET-signal, suggestive for CD95/CD95-oligomerization.
      After 120 min the FRET-signal was detected in the plasma membrane, indicating
      translocation of the CD95/CD95-oligomer to the plasma membrane. CD95/CD95
      oligomerization was abolished in presence of AG1478 or a JNK-inhibitory peptide,
      i.e. maneuvers known to prevent EGFR-catalyzed CD95-tyrosine phosphorylation.
      Transfection studies with YFP/CFP-coupled CD95-mutants, which contain
      tyrosine/phenylalanine-exchanges in positions 232 and 291 (CD95(Y232,291F)),
      revealed that at least one tyrosine (Y(232,291))-phosphorylated CD95 is required
      for CD95/CD95-oligomerization. FRET-studies in mouse embryonic fibroblasts, which
      in contrast to Huh7 express endogenous CD95, revealed that EGF, but not CD95L
      induced EGFR-homomerization, whereas CD95 ligand, but not EGF resulted in
      EGFR/CD95-heteromerization. These findings suggest that EGFR-catalyzed CD95
      tyrosine phosphorylation is involved in the CD95/CD95-oligomerization process,
      which is induced by proapoptotic stimuli and is required for apoptosis induction.

PMID- 17195093
TI  - Hypoxia-induced cell death of HepG2 cells involves a necrotic cell death mediated
      by calpain.
AB  - To elucidate mechanism of cell death in response to hypoxia, we attempted to
      compare hypoxia-induced cell death of HepG2 cells with cisplatin-induced cell
      death, which has been well characterized as a typical apoptosis. Cell death
      induced by hypoxia turned out to be different from cisplatin-mediated apoptosis
      in cell viability and cleavage patterns of caspases. Hypoxia-induced cell death
      was not associated with the activation of p53 while cisplatin-induced apoptosis
      is p53 dependent. In order to explain these differences, we tested involvement of
      micro-calpain and m-calpain in hypoxia-induced cell death. Calpains, especially
      micro-calpain, were initially cleaved by hypoxia, but not by cisplatin.
      Interestingly, the treatment of a calpain inhibitor restored PARP cleavage that
      was absent during hypoxia, indicating the recovery of activated caspase-3. The
      inhibition of calpains prevented proteolysis induced by hypoxia. In addition,
      hypoxia resulted in a necrosis-like morphology while cisplatin induced an
      apoptotic morphology. The calpain inhibitor prevented necrotic morphology induced
      by hypoxia and converted partially to apoptotic morphology with nuclear
      segmentation. Our result suggests that calpains are involved in hypoxia-induced
      cell death that is likely to be necrotic in nature and the inhibition of calpain
      switches hypoxia-induced cell death to apoptotic cell death without affecting
      cell viability.

PMID- 17195094
TI  - Cinnamtannin B-1 from bay wood exhibits antiapoptotic effects in human platelets.
AB  - Proanthocyanidins, such as cinnamtannin B-1, are polyphenolic compounds with
      antioxidant activity that induce apoptosis in a number of tumoral cells. We have
      now investigated the pro- or anti-apoptotic effects of cinnamtannin B-1 in human
      platelets. Platelet stimulation with thrombin induced cellular apoptosis, as
      detected by phosphatidylserine exposure and the activation of caspases-3 and -9.
      Pretreatment for 30 min with cinnamtannin B-1 impaired thrombin-induced apoptosis
      in platelets. Thrombin has been shown to induce H(2)O(2) generation in platelets,
      which induced similar apoptotic events than thrombin in these cells. Pretreatment
      with cinnamtannin B-1 reduced H(2)O(2)-induced phosphatidylserine exposure and
      caspase activation. Finally, platelet stimulation with thrombin induced
      translocation of caspases-3 and -9 to the cytoskeletal (Triton-insoluble)
      fraction, which is important for their activation and the development of
      apoptotic events. Pretreatment with cinnamtannin B-1 impaired translocation of
      caspases-3 and -9 to the cytoskeleton and, as a result, procaspases are
      accumulated in the Triton-soluble fraction. Our results provide evidence for the
      antiapoptotic actions of cinnamtannin B-1 in human platelets.

PMID- 17195095
TI  - Coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through
      mitochondrial injury and cleavage of eIF4GI but not DAP5/p97/NAT1.
AB  - By transfection of Coxsackievirus B3 (CVB3) individual protease gene into HeLa
      cells, we demonstrated that 2A(pro) and 3C(pro) induced apoptosis through
      multiple converging pathways. Firstly, both 2A(pro) and 3C(pro) induced caspase-8
      mediated activation of caspase-3 and dramatically reduced cell viability.
      Secondly, they both activated the intrinsic mitochondria-mediated apoptosis
      pathway leading to cytochrome c release from mitochondria and activation of
      caspase-9. However, 3C(pro) induced these events via both up-regulation of Bax
      and cleavage of Bid, and 2A(pro) induced these events via cleavage of Bid only.
      Nevertheless, neither altered Bcl-2 expression. Thirdly, both proteases induced
      cell death through cleavage or down regulation of cellular factors for
      translation and transcription: both 2A(pro) and 3C(pro) cleaved eukaryotic
      translation initiation factor 4GI but their cleavage products are different,
      indicating different cleavage sites; further, both 2A(pro) and 3C(pro) down
      regulated cyclic AMP responsive element binding protein, a transcription factor,
      with 2A(pro) exhibiting a stronger effect than 3C(pro). Surprisingly, neither
      could cleave DAP5/p97/NAT1, a translation regulator, although this cleavage was
      observed during CVB3 infection and could not be blocked by caspase inhibitor z
      VAD-fmk. Taken together, these data suggest that 2A(pro) and 3C(pro) induce
      apoptosis through both activation of proapoptotic mediators and suppression of
      translation and transcription.

PMID- 17195096
TI  - Acidic extracellular pH shifts colorectal cancer cell death from apoptosis to
      necrosis upon exposure to propionate and acetate, major end-products of the human
      probiotic propionibacteria.
AB  - The human probiotic Propionibacterium freudenreichii kills colorectal
      adenocarcinoma cells through apoptosis in vitro via its metabolites, the short
      chain fatty acids (SCFA), acetate and propionate. However, the precise
      mechanisms, the kinetics of cellular events and the impact of environmental
      factors such as pH remained to be specified. For the first time, this study
      demonstrates a major impact of a shift in extracellular pH on the mode of
      propionibacterial SCFA-induced cell death of HT-29 cells, in the pH range 5.5 to
      7.5 prevailing within the colon. Propionibacterial SCFA triggered apoptosis in
      the pH range 6.0 to 7.5, a lethal process lasting more than 96 h. Indeed at pH
      7.5, SCFA induced cell cycle arrest in the G2/M phase, followed by a sequence of
      cellular events characteristic of apoptosis. By contrast, at pH 5.5, the same
      SCFA triggered a more rapid and drastic lethal process in less than 24 h. This
      was characterised by sudden mitochondrial depolarisation, inner membrane
      permeabilisation, drastic depletion in ATP levels and ROS accumulation,
      suggesting death by necrosis. Thus, in digestive cancer prophylaxis, the observed
      pH-mediated switch between apoptosis and necrosis has to be taken into account in
      strategies involving SCFA production by propionibacteria to kill colon cancer
      cells.

PMID- 17195097
TI  - Health perception and depressive symptoms among older Korean Americans.
AB  - Given the increasing recognition of racial/ethnic health disparities, the present
      study focused on older Korean Americans. Using data from 230 older Korean
      Americans in Florida (M age = 69.8, SD = 7.05), we assessed (a) how background
      variables (demographic information and acculturation), health constraints
      (chronic conditions and functional disability), and psychosocial factors (sense
      of mastery and filial satisfaction) were associated with health perception and
      depressive symptoms; and (b) whether health perception mediated the connections
      between health constraints and depressive symptoms. We observed positive
      perceptions of health and emotional states among individuals with higher levels
      of acculturation, fewer chronic conditions, less disability, and a greater sense
      of mastery. We also found that persons who were more satisfied with their
      relationships with adult children and who had more positive health perception
      were less depressed. Additionally, the findings supported a mediation model of
      health perception in the linkages between physical and mental health. Findings
      and implications are discussed here in a cultural context.

PMID- 17195098
TI  - Recombinant luteinizing hormone supplementation to recombinant follicle
      stimulation hormone during induced ovarian stimulation in the GnRH-agonist
      protocol: a meta-analysis.
AB  - PURPOSE: to compare the efficacy of recombinant LH supplementation for controlled
      ovarian stimulation in recombinant FSH and GnRH-agonist protocol. METHODS: Search
      strategies included on-line surveys of databases. The fixed effects model was
      used for odds ratio and effect size (weighted mean difference). Four trials
      fulfilled the inclusion criteria. RESULTS: a fewer days of stimulation
      (p<0.0001), a fewer total amount of r-FSH administered (p<0.0001) and a higher
      serum estradiol levels on the day of hCG administration (p<0.0001) were observed
      for the r-LH supplementation protocol. However, differences were not observed in
      number of oocyte retrieved, number of mature oocytes, clinical pregnancy per
      oocyte retrieval, implantation and miscarriage rates. CONCLUSIONS: more
      randomized controlled trials are necessary before evidence-based recommendations
      regarding exogenous LH supplementation in ovarian stimulation protocols with FSH
      and GnRH-agonist for assisted reproduction treatment can be provided.

PMID- 17195099
TI  - In vitro tagging of embryos with nanoparticles.
AB  - PURPOSE: To develop an in vitro method for tagging embryos and to compare the
      development of the embryos after nanoparticles injection versus externally
      applied nanoparticles derived from either polystyrene or polyacrylonitrile.
      METHODS: Each mouse 1-cell embryo (the selected test-model) was either: (a)
      injected by intracytoplasmic injection or (b) co-incubated with different
      nanoparticles at 37 degrees C, 5% CO2 in air. The embryos were assessed after 2
      and 6 days of culture. RESULTS: Embryo development was similar for externally
      applied polystyrene nanoparticles and control (97.6 +/- 2.7 versus 100.0 +/- 0%)
      but different for polyacrylonitrile nanoparticles (90.0 +/- 2.8 %) on day 2.
      However, the results were similar on Day 6. Injected embryos were linked to lower
      percent development on Day 2. Few injected embryos reached blastocyst stage on
      Day 6 after a brief UV-fluorescence exposure. CONCLUSIONS: Tagging embryos by
      external polystyrene-based nanoparticles was the better method when compared with
      injected nanoparticles. Larger nanoparticles in microsphere range were easier to
      qualitate. Inhibited hatching limited their use beyond the blastocyst stage.

PMID- 17195100
TI  - Maternal-infant bedsharing: risk factors for bedsharing in a population-based
      survey of new mothers and implications for SIDS risk reduction.
AB  - OBJECTIVES: Maternal-infant bedsharing is a common but controversial practice.
      Little has been published about who bedshares in the United States. This
      information would be useful to inform public policy, to guide clinical practice
      and to help focus research. The objective was to explore the prevalence and
      determinants of bedsharing in Oregon. METHODS: Oregon Pregnancy Risk Assessment
      Monitoring System (PRAMS) surveys a population-based random sample of women after
      a live birth. Women were asked if they shared a bed with their infant "always,"
      "almost always," "sometimes" or "never." RESULTS: 1867 women completed the survey
      in 1998-99 (73.5% weighted response rate). Of the respondents, 20.5% reported
      bedsharing always, 14.7% almost always, 41.4% sometimes, and 23.4% never. In
      multivariable logistic regression, Hispanics (adjusted odds ratio [ORa] 1.69, 95%
      Confidence Interval [CI] 1.17-2.43), blacks (ORa 3.11, 95% CI 2.03-4.76) and
      Asians/Pacific Islanders (ORa 2.14, 95% CI 1.51-3.03), women who breastfed more
      than 4 weeks (ORa 2.65, 95% CI 1.72-4.08), had annual family incomes less than
      $30,000 (ORa 2.44, 95% CI 1.44-4.15), or were single (ORa 1.55, 95% CI 1.03-2.35)
      were more likely to bedshare frequently (always or almost always). Among Hispanic
      and black women, bedsharing did not vary significantly by income level.
      Bedsharing black, American Indian/Alaska Native and white infants were much more
      likely to be exposed to smoking mothers than Hispanic or Asian/Pacific Islander
      infants (p < .0001). CONCLUSIONS: Bedsharing is common in Oregon. The women most
      likely to bedshare are non-white, single, breastfeeding and low-income. Non
      economic factors are also important, particularly among blacks and Hispanics.
      Campaigns to decrease bedsharing by providing cribs may have limited
      effectiveness if mothers are bedsharing because of cultural norms.

PMID- 17195101
TI  - Jane Jacobs and urban health.

PMID- 17195103
TI  - Prevalence and stability of sexual orientation components during adolescence and
      young adulthood.
AB  - Analyses of three waves (6 years) of the National Longitudinal Survey of
      Adolescent Health data explored the prevalence and stability of sexual
      orientation and whether these two parameters varied by biologic sex, sexual
      orientation component (romantic attraction, sexual behavior, sexual identity),
      and degree of component. Prevalence rates for nonheterosexuality varied between 1
      and 15% and depended on biologic sex (higher among females), sexual orientation
      component (highest for romantic attraction), degree of component (highest if
      "mostly heterosexual" was included with identity), and the interaction of these
      (highest for nonheterosexual identity among females). Although kappa statistics
      testing for temporal stability across waves were significant, they failed to
      reach acceptable levels of agreement and could be largely attributable to the
      stability of opposite-sex rather than same-sex attraction and behavior. Migration
      over time among sexual orientation components was in both directions, from
      opposite-sex attraction and behavior to same-sex attraction and behavior and vice
      versa. To assess sexual orientation, investigators should measure multiple
      components over time or abandon the general notion of sexual orientation and
      measure only those components relevant for the research question.

PMID- 17195104
TI  - Social skills development in children with autism spectrum disorders: a review of
      the intervention research.
AB  - Social reciprocity deficits are a core feature of the autism spectrum disorders
      (ASD). This review summarizes the state of research in group-based social skills
      training programs for school-age children and adolescents with ASD. All published
      studies of group social skills interventions between 1985 and 2006 were reviewed,
      as well as dissertations examining group-based social skills intervention
      programs. To assess the state of the science, a template developed by an NIMH
      work group was applied to 14 identified studies. Based on this review, the
      empirical support for this approach is incomplete, but promising intervention
      strategies were identified. Recommendations for the design of future treatment
      trials to guide clinical practice are offered.

PMID- 17195102
TI  - The role of sexual scripts in sexual aggression and victimization.
AB  - Two longitudinal studies examined German adolescents' sexual scripts in relation
      to the normative acceptance of sexual aggression, the behavioral enactment of
      risk factors, and the experience of sexual aggression/victimization. Study 1
      comprised a sample of 283 10th and 11th grade high school students who completed
      measures of sexual scripts, normative acceptance of risk elements associated with
      sexual aggression, behavioral risk-taking, and normative acceptance of sexual
      aggression in relationships twice with a nine-month interval. General and
      individual scripts differed significantly in terms of the prevalence of risk
      elements, with individual scripts containing fewer risk elements. Normative
      acceptance of risk elements was linked to the enactment of risky behavior in
      sexual interactions and also to the normative acceptance of sexual aggression,
      both concurrently and over time. In Study 2, 232 12th and 13th grade students
      completed measures of sexual scripts and of sexual aggression or sexual
      victimization. Higher risk scores in the individual scripts were predictive of
      sexual aggression among boys and sexual victimization among girls. The findings
      were discussed in terms of the significance of sexual scripts as guidelines for
      sexual behavior.

PMID- 17195105
TI  - Nonparametric estimation of the mean function of a stochastic process with
      missing observations.
AB  - In an attempt to identify similarities between methods for estimating a mean
      function with different types of response or observation processes, we explore a
      general theoretical framework for nonparametric estimation of the mean function
      of a response process subject to incomplete observations. Special cases of the
      response process include quantitative responses and discrete state processes such
      as survival processes, counting processes and alternating binary processes. The
      incomplete data are assumed to arise from a general response-independent
      observation process, which includes right-censoring, interval censoring, periodic
      observation, and mixtures of these as special cases. We explore two criteria for
      defining nonparametric estimators, one based on the sample mean of available data
      and the other inspired by the construction of Kaplan-Meier (or product-limit)
      estimator [J. Am. Statist. Assoc. 53 (1958) 457] for right-censored survival
      data. We show that under regularity conditions the estimated mean functions
      resulting from both criteria are consistent and converge weakly to Gaussian
      processes, and provide consistent estimators of their covariance functions. We
      then evaluate these general criteria for specific responses and observation
      processes, and show how they lead to familiar estimators for some response and
      observation processes and new estimators for others. We illustrate the latter
      with data from an recently completed AIDS clinical trial.

PMID- 17195106
TI  - Simultaneous detection of five indices of hepatitis B based on an integrated
      automatic microfluidic device.
AB  - Immunophenotyping evaluation is of particular importance for the clinical
      diagnosis, therapy, and prognosis of viral hepatitis. In this study, an
      integrated micro flow device has been developed to detect the differentiated
      antigens/antibodies for immunophenotyping of viral hepatitis. The sensors were
      fabricated with plasma-polymerized ethylenediamine film (PPF) and nanometer-sized
      gold particles (nanogold) on which the different hepatitis B antigens/antibodies
      (markers) were subsequently immobilized. Monitoring the changes in the potential
      signals before and after the antigen-antibody interaction provides the basis for
      an immunoassay that is simple, rapid, and cost-effective. It permits the
      detection of hepatitis B in the dynamic concentration range of 2 orders of
      magnitude (10(-6) g x L(-1) - 10(-4) g x L(-1)). Up to 7 successive assay cycles
      with retentive sensitivity were achieved for the sensors regenerated by 8 M urea.
      Moreover, the microfluidic device was applied to evaluate a number of practical
      specimens with analytical results in acceptable agreement with those clinically
      classified. The newly proposed multiparameter analysis technique provides a
      feasible alternative tool for the diagnosis and monitoring of hepatitis B.

PMID- 17195107
TI  - A rapid DNA digestion system.
AB  - This paper presents a novel microfluidic DNA digestion system incorporating a
      high performance micro-mixer. Through the appropriate control of fixed and
      periodic switching DC electric fields, electrokinetic forces are established to
      mix the DNA and restriction enzyme samples and to drive them through the reaction
      column of the device. The experimental and numerical results show that a mixing
      performance of 98% can be achieved within a mixing channel of length 1.6 mm when
      a 150 V/cm driving voltage and a 5 Hz switching frequency are applied. The
      relationship between the mixing performance, switching frequency, and main
      applied electric field is derived. It is found that the optimal switching
      frequency depends upon the magnitude of the main applied electric field. The
      successful digestion of lambda-DNA using Eco RI restriction enzyme is
      demonstrated. The DNA-enzyme reaction is completed within 15 min in the proposed
      microfluidic system, compared to 50 min in a conventional large-scale system.
      Hence, the current device provides a valuable tool for rapid lambda-DNA
      digestion, while its mixer system delivers a simple yet effective solution for
      mixing problems in the micro-total-analysis-systems field.

PMID- 17195108
TI  - A microfluidic platform for sequential ligand labeling and cell binding analysis.
AB  - Developing biochemical and cell biological assay for screening biomolecules,
      evaluating their characteristics in biological processes, and determining their
      pharmacological effects represents a key technology in biomedical research. A
      PDMS-based integrated microfluidic platform was fabricated and tested for
      facilitating the labeling of ligand on the nanogram scale and sequential cell
      binding analysis in a manner that saves both time and reagents. Within this
      microfluidic platform, ligand labeling, cell immobolization, and optical analysis
      are performed in a miniaturized, continuous and semi-automated manner. This
      microfluidic device for ligand labeling and cell analysis is composed of two
      functional modules: (i) a circular reaction loop for fluorophore-labeling of the
      ligand and (ii) four parallel-oriented incubation chambers for immobilization of
      cells, binding of ligand to different cell populations, and optical evaluation of
      interactions between the labeled ligand and its cell targets. Epidermal growth
      factor (EGF) as the ligand and different cell lines with various levels of EGF
      receptor expression have been utilized to test the feasiblity of this
      microfluidic platform. When compared to studies with traditional Petri dish
      handling of cells and tissues, or even microwell analyses, experiments with the
      microfluidic platform described here are much less time consuming, conserve
      reagents, and are programmable, which makes these platforms a very promising new
      tool for biological studies.

PMID- 17195109
TI  - Micro-spot, UV and wetting patterning pathways for applications of biofunctional
      aminosilane-titanate coatings.
AB  - The micropatterning of functional films for biomedical applications is a key part
      of the process leading to a precise application. In the present work we present
      three different methodologies to micro-design biofunctional aminosilane-titanate
      coatings. The chemical functionality of the surface immobilized amino groups was
      initially tested by surface characterization techniques. X-ray photoelectron
      spectroscopy was used to analyze the films before and after derivatization with
      Trifluoromethylbenzaldehyde while atomic force microscopy was used to study the
      adsorption kinetics onto these hybrid films. The three micropatterning pathways
      were selected for three different kinds of applications: (1) 300 microm spots
      were satisfactorily used for oligonucleotide immobilization, (2) Masked regions
      protected from UV irradiation were intensively coated by colloidal gold
      nanoparticles creating a drastic contrast with respect to the UV exposed areas,
      and (3) radial micro stripes, used afterwards for culturing cells, were created
      onto Si substrates by wetting from modified precursor solutions. The results are
      a clear indication of the versatility of hybrid aminosilane-titanate coatings for
      biomedical applications requiring micropatterned biofunctional surfaces.

PMID- 17195110
TI  - Polymer particle-based micromolding to fabricate novel microstructures.
AB  - Conventional micromolding provides rapid and low-cost methods to fabricate
      polymer microstructures, but has limitations when producing sophisticated
      designs. To provide more versatile micromolding techniques, we developed methods
      based on filling micromolds with polymer microparticles, as opposed to polymer
      melts, to produce microstructures composed of multiple materials, having complex
      geometries, and made using mild processing conditions. Polymer microparticles of
      1 to 30 microm in size were made from PLA, PGA and PLGA using established spray
      drying and emulsion techniques either with or without encapsulating model drug
      compounds. These polymer microparticles were filled into PDMS micromolds at room
      temperature and melted or bonded together to form microstructures according to
      different protocols. Porous microstructures were fabricated by ultrasonically
      welding microparticles together in the mold while maintaining the voids inherent
      in their packing structure. Multi-layered microstructures were fabricated to have
      different compositions of polymers and encapsulated compounds located in
      different regions of the microstructures. More complex arrowhead microstructures
      were fabricated in a two-step process using a single mold. To assess possible
      applications, microstructures were designed as microneedles for minimally
      invasive drug delivery. Multi-layer microneedles were shown to insert into
      cadaver tissue and, according to design, detach from their base substrate and
      remain embedded in the tissue for controlled release drug delivery over time. We
      conclude that polymer particle-based micromolding can encapsulate compounds
      within microstructures composed of multiple materials, having complex geometries,
      and made using mild processing conditions.

PMID- 17195111
TI  - Microtubule transport, concentration and alignment in enclosed microfluidic
      channels.
AB  - The kinesin-microtubule system has emerged as a versatile model system for
      biologically-derived microscale transport. While kinesin motors in cells
      transport cargo along static microtubule tracks, for in vitro transport
      applications it is preferable to invert the system and transport cargo
      functionalized microtubules along immobilized kinesin motors. However, for
      efficient cargo transport and to enable this novel transport system to be
      interfaced with traditional microfluidics, it is important to fabricate enclosed
      microchannels that are compatible with kinesin motors and microtubules, that
      enable fluorescence imaging of microtubule movement, and that provide fluidic
      connections for sample introduction. Here we construct a three-tier hierarchical
      system of microfluidic channels that links microscale transport channels to
      macroscopic fluid connections. Shallow microchannels (5 microm wide and 1 microm
      deep) are etched in a glass substrate and bonded to a cover glass using PMMA as
      an adhesive, while intermediate channels (approximately 100 microm wide) serve as
      reservoirs and connect to 250 microm deep microchannels that hold fine gauge
      tubing for fluid injection. To demonstrate the utility of this device, we first
      show the performance of a directional rectifier that redirects 96% of moving
      microtubules and, because any microtubules that detach rapidly rebind to the
      motor-coated surface, suffers no microtubule loss over time. Second, we develop
      an approach, using a headless kinesin construct, to eliminate gradients in motor
      adsorption and microtubule binding in the enclosed channels, which enables
      precise control of kinesin density in the microchannels. Finally, we show that a
      60 microm diameter circular ring functionalized with motors concentrates and
      aligns bundles of approximately 3000 uniformly oriented microtubules, while
      suffering negligible ATP depletion. These aligned isopolar microtubules are an
      important tool for microscale transport applications and can be employed as a
      model in vitro system for studying kinesin-driven microtubule organization in
      cells.

PMID- 17195112
TI  - From grids to places.
AB  - Hafting et al. (2005) described grid cells in the dorsocaudal region of the
      medial entorhinal cortex (dMEC). These cells show a strikingly regular grid-like
      firing-pattern as a function of the position of a rat in an enclosure. Since the
      dMEC projects to the hippocampal areas containing the well-known place cells, the
      question arises whether and how the localized responses of the latter can emerge
      based on the output of grid cells. Here, we show that, starting with simulated
      grid-cells, a simple linear transformation maximizing sparseness leads to a
      localized representation similar to place fields.

PMID- 17195114
TI  - Tolerance of Drosophila flies to ibotenic acid poisons in mushrooms.
AB  - The mushroom genus Amanita has a spectrum of chemical compounds affecting
      survival and performance of animals. Ibotenic acid is one of such compounds found
      in some Amanita mushrooms. We studied the effects of ibotenic acid and its
      derivative, muscimol, on egg-to-pupa survival, pupation time, and pupal size in
      five Drosophila species (Diptera: Drosophilidae), Drosophila bizonata, Drosophila
      angularis, Drosophila brachynephros, Drosophila immigrans, and Drosophila
      melanogaster. The first three species are mycophagous and use a wide range of
      mushrooms for breeding, whereas D. immigrans and D. melanogaster are frugivorous.
      We reared fly larvae on artificial medium with 500, 250, 125, and 62.5 microg/ml
      of ibotenic acid and/or musimol. The three mycophagous species were not
      susceptible to ibotenic acid, whereas the two frugivorous species were affected.
      In experiments with D. melanogaster, muscimol was less toxic than ibotenic acid.

PMID- 17195113
TI  - The changing spectrum of diabetes in Mexican American youth.
AB  - Type 2 diabetes (T2DM) is now a pediatric disease. As in adults, it
      disproportionately affects ethnic and racial minorities, including Hispanics. The
      preponderance of Hispanics in south Texas are of Mexican American (MA) heritage.
      Over the past 16 years, we have accumulated a large cohort of children with
      diabetes. We have noted distinct differences in numerous parameters between MA
      children with T2DM and those with type 1 diabetes (T1DM). In order to explore
      these observations, we have reviewed the records of all children diagnosed with
      diabetes (n = 669) during the 9 years between January, 1990 and December, 1998
      and seen by our pediatric diabetes group. In this cohort were 329 MA, 287 non
      Hispanic whites (EA) and 53 African Americans. Compared to EA children with T1DM,
      MA children were more likely to have a parent with diabetes, to be hospitalized
      at the time of diagnosis and to lack health insurance. The differences between MA
      children with T1DM and T2DM were significant: specifically, children with T2DM
      were more likely to be female and pubertal with a body mass index >25 kg/m(2) and
      have acanthosis nigricans. Slightly more than 2/3 of the MA children with T2DM
      had at least one parent already diagnosed with T2DM. Less than 1/3 of the
      children with T2DM required hospitalization at the time of diagnosis and only a
      1/4 have private health insurance. Over this 9-year interval, the apparent
      incidence of diabetes almost tripled in south Texas with the great majority of
      that increase due to the increasing numbers of children with T2DM.

PMID- 17195115
TI  - L-DOPA increases lignification associated with Glycine max root growth
      inhibition.
AB  - L-3,4-dihydroxyphenylalanine (L: -DOPA), an allelochemical exuded from the roots
      of velvet bean [Mucuna pruriens (L.) DC. var. utilis], presents a highly
      inhibitory action to plant growth. The effects of L-DOPA on phenylalanine ammonia
      lyase (PAL, EC 4.3.1.5) and peroxidase (POD, EC 1.11.1.7) activities, and
      phenolic compound and lignin content in soybean [Glycine max (L.) Merr.] roots
      were investigated to determine the possible phytotoxic mechanism. Three-day-old
      seedlings were cultivated in half-strength Hoagland nutrient solution (pH 6.0),
      without or with 0.1 to 1.0 mM L-DOPA in a growth chamber (25 degrees C, 12-hr
      light to 12-hr darkness photoperiod, irradiance of 280 micromol m-2 s-1) for 24
      hr. In general, the length, fresh weight, and dry weight of the roots decreased,
      whereas PAL and POD activities and phenolic compound and lignin content increased
      after L-DOPA treatments. Results showed the susceptibility of soybean to L-DOPA
      and reinforce the role of this nonprotein amino acid as a strong allelochemical.
      The present findings also suggest that L-DOPA-induced inhibition in soybean roots
      may be because of a cell wall stiffening process related to the formation of
      cross-linking between cell wall polymers linked to lignin production.

PMID- 17195116
TI  - Effect of intraspecific competition and substrate type on terpene emissions from
      some Mediterranean plant species.
AB  - Competition is an important factor that has been extensively reported in the
      Mediterranean area. There is evidence that leaf terpene accumulation may vary
      between plants growing on calcareous and siliceous soils. In the present study,
      leaf terpene emissions from potted seedlings of Pinus halepensis, Cistus albidus,
      and Quercus coccifera, growing under natural environmental conditions on
      calcareous and siliceous substrates, were studied by using a bag enclosure
      method. In both substrates, seedlings were potted alone and in intraspecific
      competition, to examine the effect of substrate type and that of intraspecific
      competition on terpene emissions. The results showed that competition favored:
      (i) overall monoterpene and sesquiterpene emissions from Q. coccifera; (ii)
      overall monoterpene emissions from P. halepensis; (iii) overall sesquiterpene
      emissions from C. albidus. Substrate type affected terpene emissions to a limited
      extent and in a species-specific way. Whereas for Q. coccifera, the overall
      monoterpene emissions and that of Allo-aromadendrene were favored on siliceous
      substrate, no significant changes were found in emissions from P. halepensis.
      Only the release of AR-curcumene from C. albidus was higher on siliceous
      substrate. We also found high variability in terpene emission composition from
      the study species, particularly for P. halepensis and Q. coccifera. These two
      species released both monoterpenes and sesquiterpenes, instead of monoterpenes
      only, as shown in previous studies.

PMID- 17195117
TI  - Role of catechol structure in the adsorption and transformation reactions of L
      DOPA in soils.
AB  - 3-(3',4'-Dihydroxyphenyl)-L-alanine (L-DOPA), which is synthesized in velvet bean
      (Mucuna pruriens), inhibits plant growth. The concentration of L-DOPA in soil is
      reduced by adsorption and transformation reactions, which can result in the
      reduction of its plant-growth-inhibitory activity. To determine which part of the
      L-DOPA structure is involved in the adsorption and soil transformation reactions,
      we compared the kinetics of L-DOPA disappearance in a volcanic ash soil with that
      of L-phenylalanine (3-phenyl-L-alanine) and L-tyrosine (3-(4'-hydroxyphenyl)-L
      alanine), compounds that are similar in structure to L-DOPA but do not have a
      catechol (o-dihydroxybenzene) moiety. L-Phenylalanine and L-tyrosine were not
      adsorbed and transformed in the soil at equilibrium pH values between 4 and 7.
      These results suggest that the adsorption and transformation reactions of L-DOPA
      in the soil involve the catechol moiety and not the amino and carboxylic acid
      groups, which are common to all three compounds. Like L-DOPA, (+)-catechin,
      another allelochemical that contains a catechol moiety, underwent adsorption and
      soil transformation reactions. Thus, we concluded that the concentrations of
      allelochemicals bearing a catechol moiety in soils will decrease rapidly owing to
      adsorption and transformation reactions, and this decrease will be faster in
      soils with a high pH value or high adsorption ability. Owing to this decrease in
      concentration, allelopathic phenomena may not occur.

PMID- 17195118
TI  - Scopolamine in Brugmansia suaveolens (Solanaceae): defense, allocation, costs,
      and induced response.
AB  - Brugmansia suaveolens (Solanaceae) contains tropane alkaloids (TAs), which can
      act as chemical defenses. Selective pressures might modulate the allocation of
      alkaloids within the plant, as postulated by optimal-defense theory. By tracing
      scopolamine, the most abundant TA in this species, we found that scopolamine in
      an artificial diet, in concentrations similar to those in leaves of B.
      suaveolens, increased mortality and prolonged developmental time of the larvae of
      the generalist noctuid moth Spodoptera frugiperda. A diet of undamaged leaves of
      B. suaveolens also showed a large negative effect on the growth of larvae of S.
      frugiperda compared to a diet of leaves of Ricinus communis, a species that did
      not have negative effects on this moth; more valuable plant parts, such as young
      leaves, flowers, and unripe fruits with seeds, have higher scopolamine
      concentrations than other tissues; leaves of B. suaveolens increase their content
      of scopolamine after artificial damage. The highest induction was found 24 hr
      after the damage, and after that, scopolamine content decreased to constitutive
      levels. This increase represented a cost, because in another experiment, a
      treatment with methyl jasmonate, an elicitor hormone, increased scopolamine
      production 9.5-fold and decreased leaf growth 2.3-fold; a diet of artificially
      damaged leaves of B. suaveolens showed a negative effect on the growth of larvae
      of S. furgiperda compared to undamaged leaves, suggesting that damage by
      herbivores induces resistance. Our data are in line with the optimal-defense
      theory, but experiments in the field with herbivores that share an evolutionary
      history with B. suaveolens must be undertaken to understand the dynamics of TA
      allocation in response to herbivory.

PMID- 17195119
TI  - Placement of gastrostomy tubes in patients with ventriculoperitoneal shunts does
      not result in increased incidence of shunt infection or decreased survival.
AB  - The objective of this study was to examine if G-tube (G-tube) placement in
      patients with ventriculoperitoneal (VP) shunts results in shunt infection or
      impacts patient survival. We performed a retrospective cohort study. Patients
      underwent VP shunt and G-tube placement. Incidence of shunt infection and patient
      survival were calculated. Fifty-five patients qualified for the study. Shunt
      infection occurred in seven patients (12.5%). The incidence of shunt infection
      did not differ between surgically placed G-tubes (2/7=29%) and PEG tubes
      (5/7=71%; P=0.69). There was no difference in the risk of VP infection based on
      the order of placement (OR=0.61 [0.12-3.02]; P=0.69). No predictors for shunt
      infection were identified. Kaplan-Meier mortality estimates demonstrated a 21% 1
      year mortality rate. There were no predictors of patient survival. We conclude
      that placement of G-tubes in patients with shunts is safe. The order of placement
      of G-tube and VP shunt does not affect the incidence of shunt infection or
      survival.

PMID- 17195120
TI  - Participation of capsaicin-sensitive afferent nerves in the gastric mucosa of
      patients with Helicobacter pylori-positive or-negative chronic gastritis.
AB  - Capsaicin-sensitive afferent nerves (CSANs) are involved in the protection of
      gastric mucosa. To clarify the role of CSANs in human Helicobacter pylori
      negative or -positive chronic gastritis, after bacterium detection by rapid
      urease test, (14)C urea breath test, and specific histological staining, the
      immunodistribution of capsaicin receptor, calcitonin gene-related peptide (CGRP),
      and substance P (SP) was studied in 21 H. pylori-positive and 30 H. pylori
      negative patients with chronic gastritis and 20 patients with functional
      dyspepsia (as histologically healthy controls). The expression of capsaicin
      receptor, CGRP, and SP was significantly higher in the mucosa of patients with
      chronic gastritis than in controls, however, no significant difference was
      obtained in the immunodistribution in patients with H. pylori-negative versus H.
      pylori-positive gastritis. In conclusion, CSANs participate in the development of
      human gastritis, however, their participation does not depend on the presence of
      Helicobacter pylori as a causative factor.

PMID- 17195126
TI  - MRI findings in the subchondral bone marrow: a discussion of conditions including
      transient osteoporosis, transient bone marrow edema syndrome, SONK, and shifting
      bone marrow edema of the knee.
AB  - Bone marrow edema signal can be seen in many settings ranging from trauma and
      arthritis to less common conditions including transient osteoporosis, transient
      bone marrow edema syndrome, true osteonecrosis, spontaneous osteonecrosis, and
      shifting bone marrow edema. Terms such as spontaneous osteonecrosis of the knee
      (SONK) appear frequently in the radiology and orthopedics literature but are
      rarely described on true, histologic basis. This article reviews the less
      frequently encountered and less well understood entities and explores their
      potential pathophysiologies and significance.

PMID- 17195127
TI  - Magnetic resonance imaging of the rotator cuff interval.
AB  - The rotator cuff interval (RCI) is an important and anatomically complex region
      of the rotator cuff that is critically important to normal glenohumeral function.
      Recognition of common pathologies in this region on imaging examinations is
      especially important as injuries may be difficult to detect on clinical
      examination and even at arthroscopy. Familiarity with the magnetic resonance
      imaging appearance of the normal and abnormal RCI and the ability to convey
      findings to orthopedic and sports medicine referrers are essential to facilitate
      prompt creation of effective treatment plans.

PMID- 17195121
TI  - Enhanced oxidative stress and leucocyte activation in neoplastic tissues of the
      colon.
AB  - Excess of intracellular reactive oxygen species results in an environment that
      may modulate gene expression, or damage cellular molecules. These events are
      assumed to contribute to the process of carcinogenesis. In the present study, we
      measured the extent of lipid peroxidation and antioxidative status in colonic
      tumors and normal colonic mucosa obtained from 25 patients with colorectal
      carcinoma. Levels of lipid peroxides (PD) and of thiobarbituric acid reactive
      substances (TBARS) were significantly increased, by 54 and 59%, respectively, in
      tissue specimens obtained from the colonic tumor as compared with normal colonic
      mucosa (PD, 2.78+/-0.31 versus 1.81+/-0.29 nmol/mg tissue, TBARS, 0.86+/-0.1
      versus 0.54+/-0.08 nmol/mg tissue). Activities of the antioxidant enzymes
      catalase and glutathione peroxidase (GPx) were also higher (by 67 and 29%,
      respectively) than in normal mucosa, probably in response to the increased free
      radical stress occurring in cancerous tissues. Myeloperoxidase (MPO) and
      adenosine deaminase (ADA) are markers of activated leukocytes and are related to
      the production of oxygen free radicals by these cells. Their activities were
      significantly elevated in the neoplastic tissue as compared to the normal tissue
      (MPO, 7.4+/-1.5 versus 4.1+/-0.95 U/mg tissue, ADA, 4.17+/-0.65 versus 2.99+/
      0.80 U/g tissue), suggesting a possible involvement of activated leukocytes in
      the enhanced oxidative stress in the cancerous tissue. Our results demonstrate an
      enhanced oxidative stress in the neoplastic tissue. Leukocyte activation was also
      higher in the carcinogenic tissue, indicating a possible contribution of these
      cells to a further oxidative stress-derived tissue injury. These observations add
      to previous studies and may encourage therapeutic trials with antioxidants as a
      means of preventing colorectal cancer and preventing further tissue injury in the
      neoplastic tissue and its surroundings.

PMID- 17195128
TI  - MR imaging of groin pain in the athlete.
AB  - Groin pain is a frequently encountered symptom in the athlete. The differential
      diagnosis for an athlete presenting with groin pain is broad and diagnostic
      imaging plays a crucial role in reaching the correct diagnosis, allowing
      appropriate therapy to be instituted. In this article we present the radiological
      differential diagnosis of athletes presenting with groin pain. The common
      mechanisms of injury, presenting symptoms, and imaging findings for each of these
      entities are addressed.

PMID- 17195129
TI  - Hip MR arthrography and femoroacetabular impingement.
AB  - Hip pain is a common complaint among athletes of all ages. Advances in imaging
      and treatment are changing the paradigm of evaluation and management of hip pain.
      The role of abnormal femoral and acetabular morphology and lesions of the
      acetabular labrum and cartilage is increasingly recognized as being crucial in
      the development of degenerative change. In addition, femoroacetabular impingement
      is increasingly recognized as an etiologic factor in hip pain. This article
      discusses techniques of hip magnetic resonance (MR) arthrography, normal anatomy
      seen at hip MR arthrography, common intra-articular pathologies in patients with
      hip pain, and imaging findings of femoroacetabular impingement.

PMID- 17195130
TI  - MRI of the posterolateral corner of the knee: normal appearance and patterns of
      injury.
AB  - The posterolateral corner (PLC) of the knee is a complex area, previously poorly
      understood by radiologists. Numerous structures make up the PLC, whose evaluation
      is difficult because of the variable presence of the individual components, their
      intimate and commonly overlapping insertions, and their oblique course on
      traditional imaging planes. The clinical relevance of PLC injuries, especially
      the infrequently repaired "minor" components, adds to the confusion. Our purpose
      is to review the anatomy, imaging, clinical evaluation, and treatment options for
      PLC injuries.

PMID- 17195131
TI  - MR imaging of the postoperative meniscus: repair, resection, and replacement.
AB  - Meniscal surgery is one of the most common orthopedic procedures performed in
      clinical practice today. Increasing awareness of the importance of the meniscus
      in knee function and stability has resulted in abandonment of the once common
      complete meniscectomy in favor of meniscus-preserving surgeries and, in some
      circumstances, meniscal replacement. Although the accuracy of magnetic resonance
      imaging in the diagnosis of meniscal tears is well established, imaging of the
      postoperative meniscus has proved more challenging, with debate about the optimal
      imaging technique. This article discusses normal meniscal anatomy and
      biomechanics to serve as the background for understanding meniscal pathology and
      treatment. This is followed by a review of meniscal surgery, with emphasis placed
      on meniscal repair, partial meniscectomy, and meniscal transplantation. Finally,
      imaging modalities utilized in the assessment of the postoperative meniscus are
      reviewed, including their advantages and disadvantages.

PMID- 17195133
TI  - Idiopathic interstitial pneumonia: a clinicopathological perspective.
AB  - Idiopathic interstitial pneumonia (IIP) represents a diverse group of lung
      disorders with variable prognoses and responses to therapy. As the name implies,
      the etiology is unknown. In the more severe forms of IIP, such as idiopathic
      pulmonary fibrosis and acute interstitial pneumonia, no effective therapies have
      been identified. In this perspective, the spatiotemporal variability in the
      histopathology of these disorders is discussed. It is proposed that common
      etiologies or injurious agents may produce variable histopathological "reactions"
      in the lung due to complex interactions between the host (genetic/epigenetic
      factors, age) and environmental factors. Accurate clinical and biological
      phenotyping may be necessary to stratify or group patients who are most likely to
      respond to specific modes of therapy.

PMID- 17195134
TI  - Host-environment interactions in pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the
      pulmonary parenchyma, leading to respiratory failure and death. Several
      epidemiological and theoretical observations link the pathogenesis of this
      disease to environmental injury to the lungs. We discuss the theoretical
      framework of this hypothesis and we present data in support of the concept that
      genetic and nongenetic host susceptibility may interact with repetitive
      environmental injury to lead to IPF.

PMID- 17195135
TI  - Genetic factors in pulmonary fibrotic disorders.
AB  - Identifying genetic determinants of pulmonary fibrotic disorders remains at an
      early stage of evolution. It is now well-recognized that "pulmonary fibrosis"
      covers a broad range of lung diseases, including most topically the idiopathic
      interstitial pneumonias that have been classified recently. Additionally, it is
      recognized that the fibrosing lung disorders that are seen in the rheumatological
      diseases, notably systemic sclerosis, are quite different from those of the
      idiopathic variety. Defining clinical phenotype is an important prerequisite to
      the identification of genetic determinants associated with individual diseases,
      but it is important to acknowledge that there may be determinants of global lung
      fibrosis and that other factors drive diseases down specific, more individual
      disease pathways. Current association studies are encouraging but far from
      conclusive for a variety of reasons, including small numbers, poor controls, and
      curious candidate selection. The results of the ongoing multicenter familial
      linkage study in the United States should provide several candidate genes that
      will spur further studies of sporadic disease in, it is hoped, a more
      internationally coordinated effort.

PMID- 17195136
TI  - Inflammation and angiogenesis in fibrotic lung disease.
AB  - The pathogenesis of pulmonary fibrosis is poorly understood. Although
      inflammation has been presumed to have an important role in the development of
      fibrosis this has been questioned recently, particularly with regard to
      idiopathic pulmonary fibrosis (IPF). It is, however, increasingly recognized that
      the polarization of the inflammatory response toward a type 2 phenotype supports
      fibroproliferation. Increased attention has been on the role of noninflammatory
      structural cells such as the fibroblast, myofibroblast, epithelial cell, and
      endothelial cells. Furthermore, the origin of these cells appears to be
      multifactorial and includes resident cells, bone marrow-derived cells, and
      epithelial to mesenchymal transition. Increasing evidence supports the presence
      of vascular remodeling in fibrotic lung disease, although the precise role in the
      pathogenesis of fibrosis remains to be determined. Therefore, the pathogenesis of
      pulmonary fibrosis is complex and involves the interaction of multiple cell types
      and compartments within the lung.

PMID- 17195138
TI  - Histopathology of pulmonary fibrotic disorders.
AB  - Interstitial lung diseases encompass a broad spectrum of disorders that vary
      greatly in their clinical presentation, natural history, pathology, pathogenesis,
      prognosis, and treatment. Their correct classification requires integration of
      clinical, radiological, and pathological findings. Although these disorders may
      be well defined, interpretation of lung biopsy findings is often difficult, with
      surprisingly significant interobserver variability. This article reviews the
      histopathology of the major interstitial lung diseases, including the idiopathic
      interstitial pneumonias and pulmonary fibrotic disorders associated with collagen
      vascular diseases and smoking. In addition, the differential diagnosis of each of
      these disorders is discussed.

PMID- 17195139
TI  - High-resolution computed tomography of interstitial pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF), also referred to as cryptogenic fibrosing
      alveolitis (CFA), is the clinical-radiological-pathological syndrome associated
      with the most common form of fibrosing interstitial pneumonia, usual interstitial
      pneumonia (UIP). Unfortunately, the diagnosis of IPF carries with it a relatively
      poor prognosis. The characteristic features on high-resolution computed
      tomography (HRCT), consisting of reticular abnormality and honeycombing with
      basal and peripheral predominance, are virtually diagnostic within the correct
      clinical context. The extent of fibrosis on HRCT is an important prognostic
      indicator. When ground-glass attenuation is seen in patients with IPF, it
      commonly progresses to fibrosis and honeycombing. Complications of IPF include
      accelerated progression and deterioration, lung cancer, spontaneous air leak, and
      secondary infection. This article discusses the key imaging features as
      correlated with histopathology, differential diagnosis, complications, and follow
      up evaluation of idiopathic pulmonary fibrosis.

PMID- 17195140
TI  - Usual interstitial pneumonia.
AB  - Usual interstitial pneumonia (UIP) is a distinct histological lesion observed in
      idiopathic pulmonary fibrosis (IPF) but can be found in other etiologies. The
      diagnosis of UIP can be established by surgical lung biopsy or by high-resolution
      thin-section computed tomographic (CT) scans (provided the radiographic features
      are classical). Historically, patients labeled as "IPF" encompassed a group of
      disorders, including UIP as well as other idiopathic interstitial pneumonias that
      differ from UIP in prognosis and responsiveness to therapy. Current
      recommendations from international consensus statements restrict the term IPF to
      patients with idiopathic UIP. The inciting cause(s) and pathogenesis of UIP have
      not been elucidated, but alveolar epithelial cell injury and dysregulation or
      altered phenotypic expression of fibroblasts are key elements. Inflammatory cells
      may play minor roles in initiating or propagating the fibrotic process. The
      prognosis of UIP is poor. Mean survival following diagnosis approximates 3 years.
      Current therapies are of unproven value. Corticosteroids or immunosuppressive
      agents have been most often used, but data affirming benefit are lacking. Lung
      transplantation is a viable option for patients failing medical therapy. This
      review discusses diagnostic criteria for UIP (both histopathological and
      radiographic), natural history and clinical course, and therapeutic approaches
      (both current and future).

PMID- 17195141
TI  - Nonspecific interstitial pneumonia.
AB  - Nonspecific interstitial pneumonia (NSIP) describes a histopathologic pattern
      that can be seen in patients with immunodeficiency, drug or environmental
      exposures, and connective tissue diseases. The clinical diagnosis of NSIP,
      however, should be reserved for idiopathic cases in which no causative factor is
      identified. Patients typically present with cough, dyspnea, restrictive pulmonary
      physiology with decreased gas transfer, and ground-glass infiltrates on high
      resolution computed tomography (HRCT). Response to immunosuppressive therapy is
      often successful; however, patients with progressive disease are at increased
      risk of subsequent mortality and should be considered for alternative treatment
      strategies such as lung transplantation.

PMID- 17195142
TI  - Acute interstitial pneumonia and acute exacerbations of idiopathic pulmonary
      fibrosis.
AB  - Acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic
      pulmonary fibrosis (AEIPF) are similar respiratory disorders characterized by the
      rapid development of progressive dyspnea and cough. Both frequently lead to
      respiratory failure and death. Pathologically, each is characterized by the
      presence of a diffuse alveolar damage (DAD) pattern; in AIP, DAD is the sole
      pattern, whereas in AEIPF DAD is superimposed upon a background usual
      interstitial pneumonia. They differ in that patients with AEIPF have preexisting
      idiopathic pulmonary fibrosis, whereas patients with AIP have no predisposing
      disorders to account for their disease. Because both presentations overlap with
      multiple other causes of acute lung injury, a comprehensive evaluation is
      necessary to rule out disorders such as overwhelming infection or congestive
      heart failure. Although a confident diagnosis can be achieved without it, a
      surgical lung biopsy is necessary to provide a definitive diagnosis. Despite
      minimal evidence, glucocorticoids are frequently begun once microbiological
      evaluation confirms the absence of infection. Despite therapy, the case fatality
      rate ranges up to 70% for both, with most patients dying in the first 2 weeks.
      Survivors of the acute event can recover to their previous baseline; however,
      most AIP survivors will stabilize with some functional impairment, whereas in
      those with AEIPF, progressive fibrosis with functional deterioration is the rule.

PMID- 17195137
TI  - Epithelial-mesenchymal interactions in pulmonary fibrosis.
AB  - Pulmonary fibrosis represents the sequelae of a variety of acute and chronic lung
      injuries of known and unknown etiologies. Tissue specimens obtained from patients
      with pulmonary fibrosis, regardless of the etiology, consistently show evidence
      of an ongoing wound-repair response. Epithelial-mesenchymal interactions have
      critical roles in normal lung development, tissue repair processes, and fibrosis.
      Current hypotheses propose that dysregulated function of, and impaired
      communication between, epithelial and mesenchymal cells prevent resolution of the
      wound-repair response and contribute to the pathobiology of pulmonary fibrosis.
      This hypothesis is supported by abundant evidence from patients, animal models,
      and cell-culture studies demonstrating abnormalities in epithelial cell and
      mesenchymal cell activities including proliferation, differentiation, and
      survival. This article reviews the aberrant epithelial and mesenchymal cellular
      phenotypes found in the context of pulmonary fibrosis and discusses the
      mechanisms that perpetuate these cellular phenotypes.

PMID- 17195143
TI  - Treatment of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive lung disease in
      most cases, and effective treatment is still lacking. This review examines the
      current status of treatment options and complexities in the management of
      patients with IPF. Although optimal therapy for IPF has not been identified,
      ongoing research efforts warrant reason for optimism. Current management of IPF
      includes not only judicious use of available pharmacological agents tailored to
      individual circumstances but also patient education through realistic assessment
      of prognosis, discussion of pros and cons of pharmacotherapy, early consideration
      of lung transplantation when applicable, treatment of complications, supportive
      care, and encouragement to participate in clinical trials.

PMID- 17195144
TI  - Cord around the neck: should it be severed at delivery? A randomized controlled
      study.
AB  - Umbilical cords often become encircled around portions of the fetus, usually the
      neck. The incidence ranges from 21% in one loop to 0.2% in three loops. In the
      present study, we assessed the practice of severing the cord, which was encircled
      once around the neck of the fetus, after delivery of the anterior shoulder and
      prior to extraction of the body. This was a prospective, randomized, controlled
      study. The study and the control groups included 30 women each. Cord around the
      neck was diagnosed during labor by ultrasound. It was cut intentionally in the
      study group and left intact in the control group. Demographic data were obtained.
      The course of labor was assessed. Neonatal outcomes measured were cord pH, Apgar
      scores at 5 minutes, and need for resuscitation. Length of maternal and neonatal
      hospitalization was determined. No differences were found between the study and
      the control group before, during, and after labor regarding perinatal variables
      such as meconium-stained amniotic fluid, fetal heart rate patterns, Apgar scores
      at 5 minutes, and umbilical cord pH after delivery (7.29 +/- 0.07 [SD] in the
      study group and 7.32 +/- 0.06 [SD] in the controls; p=0.1). Single nuchal
      encirclement by the umbilical cord during labor, after delivery of the anterior
      shoulder, can be severed or left intact. We could not detect any adverse
      perinatal outcome in such deliveries.

PMID- 17195145
TI  - Intestinal stenosis caused by perinatal intussusception in a full-term neonate.
AB  - Perinatal intussusception is rare, but can be seen in both premature and full
      term neonates. The symptoms and signs are similar to those seen in necrotizing
      enterocolitis (NEC), causing the diagnosis of intussusception to be delayed. We
      report a case of intussusception that presented with features suggestive of NEC
      in a 3.4-kg, full-term female neonate. Diagnosis of intussusception was made with
      a plain abdominal x-ray and abdominal ultrasound. During surgery, an ileocolic
      intussusception with intestinal stenosis was found. Although intestinal stenosis
      and atresia are commonly found in premature infants, these entities can also
      occur in a full-term infant. Early diagnosis is needed to reduce the high
      morbidity and mortality in these infants.

PMID- 17195146
TI  - Shirodkar versus McDonald cerclage for the prevention of preterm birth in women
      with short cervical length.
AB  - The efficacy of Shirodkar cerclage was compared with that of the McDonald
      procedure for the prevention of preterm birth (PTB) in women with a short cervix.
      Secondary analysis using data from all published randomized trials including
      women with a short cervical length (CL) was performed comparing the use of
      Shirodkar versus McDonald sutures. Analysis was limited to singletons with short
      CL on transvaginal ultrasound. The primary outcome measure was PTB < 33 weeks.
      Statistical analysis was performed using bivariate and multivariable techniques.
      From 607 women randomly assigned in the study, 277 met our inclusion criteria;
      127 received Shirodkar and 150 women received McDonald sutures. The mean ( +/-
      standard deviation) gestational age at delivery was 35.0 +/- 5.3 versus 36.3 +/-
      4.7 for the Shirodkar versus McDonald groups, respectively ( p< 0.02). PTB < 33
      weeks was seen in 61 (22%) of 277 women; 26 (20%) of 127 in the Shirodkar and 35
      (23%) of 150 in the McDonald groups, respectively (odds ratio [OR], 0.85; 95%
      confidence interval [CI], 0.5 to 1.6). On adjusting for confounders using
      logistic regression modeling, no significant difference in PTB < 33 weeks was
      found between the two groups (OR, 0.55; 95% CI, 0.2 to 1.3). In women with short
      cervical length randomly assigned to receiving cerclage, no significant
      difference in prevention of PTB was observed using Shirodkar or McDonald's
      procedures.

PMID- 17195147
TI  - Hypothermia for the treatment of neonatal ischemic encephalopathy: is the genie
      out of the bottle?
AB  - Evidence suggests that hypothermia for hypoxic ischemic encephalopathy in the
      term neonate may decrease the risk of death or neurodevelopmental impairment. The
      objective of this study was to determine how hypothermia has been incorporated
      into practice. An anonymous survey was sent to medical directors of United States
      neonatal intensive care units (NICUs) in October 2005. We received completed
      surveys from 441 (54.5%) of 809 of NICUs. Only 6.4% of respondents used
      hypothermia. The most common method was total body cooling (64.3%) compared with
      head cooling (25%) or both (10.7%). At centers that did not offer hypothermia,
      29% transferred infants to an institution that did. Centers that offered
      hypothermia were more likely at academic institutions (76.9%) compared with
      private practices (11.5%; p < 0.001). Hypothermia was more likely offered at
      institutions that offered extracorporeal membrane oxygenation (ECMO; 57%) than
      centers where ECMO was not offered (43%; p < 0.001). There has not been
      widespread use of hypothermia. There are a variety of protocols used. As results
      of further outcome studies become available, educational efforts and national
      practice guidelines will be essential.

PMID- 17195148
TI  - Prognostic factors and clinical features in liveborn neonates with hydrops
      fetalis.
AB  - The purpose of this study was to delineate the etiology and the clinical features
      of liveborn neonates with hydrops fetalis, and to explore the prognostic factors
      for survival. Medical records of 28 liveborn neonates with hydrops fetalis
      between April 1995 and March 2005 were reviewed retrospectively. Demographic
      data, clinical manifestations, laboratory findings, and outcomes were analyzed.
      Most patients presented with pleural effusions (21 of 28) and ascites (22 of 28).
      The majority of patients had hydrops due to cardiovascular diseases (seven of
      28), hematologic disorders (six of 28), lymphatic malformations (six of 28), and
      idiopathic origins (six of 28). The overall survival rate was 50% and was highest
      (83%) in infants with lymphatic malformations. By univariate analysis, risk
      factors for mortality are earlier ages at diagnosis and at birth, low Apgar
      scores, need for resuscitation in the delivery room, low serum albumin level, and
      severe acidemia. After using stepwise multiple logistic regression analysis, the
      most significant factors associated with fatality were younger gestational age at
      birth and lower serum albumin level. Hydrops fetalis remains a complex condition
      with a high mortality rate. Hydrops resulting from lymphatic malformations has a
      favorable outcome. Preterm birth at less than 34 weeks and serum albumin
      concentration lower than 2 g/dL are two poor prognostic factors for survival.

PMID- 17195149
TI  - Routine cervical length in twins and perinatal outcomes.
AB  - A retrospective review of twin gestations was undertaken to evaluate whether
      routine cervical lengths (CLs) in such instances change pregnancy outcome. Data
      were collected from the ultrasound database and chart review. Exclusion criteria
      included twins reduced to singletons, twins not delivering at our institution,
      and incomplete information. Twin gestations with a CL were compared with those
      without a CL. Outcomes of interest included gestational age (GA) at delivery,
      preterm delivery (PTD), antepartum admissions, antepartum length of stay (LOS),
      cerclage placement, birthweight, neonatal intensive care unit admissions, and
      neonatal LOS. Two hundred sixty-two patients met inclusion criteria. Of those,
      184 had CLs and 78 did not. Comparing the CL to the no-CL group, there were no
      differences with respect to GA at delivery (34.8 versus 35.3 weeks; p=0.35),
      antepartum admissions (32.1 versus 23.1%; p=0.16), cerclage placement (7.1 versus
      1.3%; p=0.06), or tocolysis use (28.6 versus 21.8%; p=0.26). There was no
      difference between the two groups with respect to preterm labor (26 versus 19%;
      p=0.25), PTD < 28 weeks (8.2 versus 3.9%; p=0.21), PTD < 34 weeks (26.1 versus
      25.6%; p=0.94), or PTD < 37 weeks (76.1 versus 70.5%; p=0.34). The only
      significant difference was antepartum LOS (34.5 versus 31.3 days; p< 0.001).
      There were no differences in neonatal outcomes. Routine CL did not improve
      perinatal outcome but increased maternal antepartum LOS.

PMID- 17195150
TI  - Does hospitalization prevent preterm delivery in the patient with a short cervix?
AB  - This study considers whether admission to the hospital of a patient diagnosed
      with a short cervix delayed delivery, prevented preterm delivery, and/or
      decreased the rate of change in the cervical length (CL) on follow-up
      measurements. The design was a retrospective cohort study of women carrying
      singleton pregnancies with cervical lengths <or= 25 mm at gestational ages 16 to
      28 weeks managed expectantly from July 2002 through July 2005. Eighty-two
      patients met criteria for inclusion, 26 (32%) of whom were hospitalized. On
      univariate analysis, hospitalization correlated with delivery < 34 weeks (
      p=0.027), an earlier gestational age (GA) at delivery ( p=0.046), and a shorter
      time from diagnosis to delivery ( p< .001). Multivariate regression analysis of
      significant factors (age, prior preterm births, initial CL, GA at diagnosis, and
      hospitalization) showed a correlation between hospitalization and increased rate
      of cervical shortening ( p=0.005), and a trend toward hospitalization as an
      independent risk factor for delivery less than 34 weeks ( p=0.066), an earlier GA
      at delivery ( p=0.058), and a shorter time from diagnosis to delivery ( p=0.078).
      There also was no benefit seen from hospitalization when the initial CL was < 15
      mm, although we were underpowered for this analysis. Admission to the hospital
      was not associated with a decreased rate of preterm delivery and there was a
      trend toward hospitalization as an independent risk factor for delivery at < 34
      weeks, an earlier GA at delivery, and a shorter time from diagnosis to delivery.
      Hospitalization was independently associated with an increased rate of cervical
      shortening.

PMID- 17195151
TI  - Serum caffeine concentrations in preterm neonates.
AB  - Caffeine therapy reduces apnea of prematurity, promotes successful extubation
      from invasive positive-pressure ventilation, and decreases the incidence of
      bronchopulmonary dysplasia. The recommended dosing for caffeine is a loading dose
      of 20 mg/kg followed by a 5 mg/kg/d maintenance dose. However, controversy exists
      about the optimal dosing regimen and data on serum caffeine concentrations in
      extremely immature infants are scant. We determined serum caffeine concentrations
      approximately 7 days after starting therapy with a 20 or 25 mg/kg loading dose
      and a 6 mg/kg/d maintenance dose in 154 infants with a mean gestational age of 29
      weeks. The 25th to 75th percentile range for the serum caffeine concentrations
      with the two dosing regimens was equivalent, approximately 18 to 23 mg/L. Within
      the first 14 postnatal days, the serum caffeine concentrations were not dependent
      on postmenstrual age, weight, or postnatal age, and were in a range that is safe
      and therapeutic. This latter observation remained valid over the ranges of
      clinical and laboratory assessments of renal and hepatic functions that are
      usually found in practice. Routine measurement of steady-state serum caffeine
      concentrations in infants 24 to 35 weeks gestational age is not required in the
      absence of ongoing apnea/hypopnea or signs compatible with toxicity.

PMID- 17195152
TI  - Prediction of shoulder dystocia using multivariate analysis.
AB  - We evaluated the use of multivariate analysis in the prediction of shoulder
      dystocia (SD). One hundred consecutive cases with SD were matched with 100
      controls without dystocia. All patients had term, vaginal delivery. Multivariate
      analysis was used to identify independent variables significantly related to
      shoulder dystocia. The regression coefficients for the identified factors were
      used to calculate a composite score from which receiver operating characteristics
      (ROC) curves were derived. Birthweight (BW), 1-hour Glucola (GLU), operative
      vaginal delivery (OVD), and height of fundus (HOF) were related independently to
      SD. The sensitivity and specificity reached 84 and 80%, respectively, with BW +
      GLU + OVD. Significant associations persisted when HOF and carbohydrate
      intolerance were substituted for BW and GLU, respectively. SD is independently
      associated with BW, GLU, and OVD, and may be predicted with clinically acceptable
      accuracy using multiple variables. This model may be useful in the design of
      prospective studies for managing suspected macrosomia.

PMID- 17195154
TI  - Nearest-neighbor nonparametric method for estimating the configurational entropy
      of complex molecules.
AB  - A method for estimating the configurational (i.e., non-kinetic) part of the
      entropy of internal motion in complex molecules is introduced that does not
      assume any particular parametric form for the underlying probability density
      function. It is based on the nearest-neighbor (NN) distances of the points of a
      sample of internal molecular coordinates obtained by a computer simulation of a
      given molecule. As the method does not make any assumptions about the underlying
      potential energy function, it accounts fully for any anharmonicity of internal
      molecular motion. It provides an asymptotically unbiased and consistent estimate
      of the configurational part of the entropy of the internal degrees of freedom of
      the molecule. The NN method is illustrated by estimating the configurational
      entropy of internal rotation of capsaicin and two stereoisomers of tartaric acid,
      and by providing a much closer upper bound on the configurational entropy of
      internal rotation of a pentapeptide molecule than that obtained by the standard
      quasi-harmonic method. As a measure of dependence between any two internal
      molecular coordinates, a general coefficient of association based on the
      information-theoretic quantity of mutual information is proposed. Using NN
      estimates of this measure, statistical clustering procedures can be employed to
      group the coordinates into clusters of manageable dimensions and characterized by
      minimal dependence between coordinates belonging to different clusters.

PMID- 17195153
TI  - Transcription and epigenetic profile of the promoter, first exon and first intron
      of the human tyrosine hydroxylase gene.
AB  - The transcriptional and chromatin profile of the promoter, first exon and first
      intron of the human TH gene were analyzed in human neuroblastoma BE(2)-C-16 and
      human renal carcinoma 293FT cell lines. The latter is a cell culture system that
      is not permissive for TH gene expression, whereas the former has a 50% cell
      fraction that tests positive for TH. The engineering of a 6.3 kb recombinant
      human TH promoter revealed the presence of repressors of transcription between
      positions (-6,244/-194). The addition of a 1.2 kb fragment of the first intron of
      the human TH gene (+730/+1,653) enhanced transcriptional activity of the
      recombinant promoter. However, both constructs were not specific for TH-positive
      BE(2)-C-16 cells. Chromatin immunoprecipitation (Chip) analysis was carried out
      on BE(2)-C-16 and 293FT cells to probe sequences of promoter, first exon and
      first intron of the human TH gene from position (-448/+1,204). The presence of
      nucleosomes was observed approximately from position (-20/+473) in both cell
      lines. Chip analysis was then conducted to determine the acetylation of various
      lysine residues of H3 and H4 in both cell lines. All analyzed lysine residues of
      H3 and H4 were acetylated in BE(2)-C-16 cells, whereas 293FT cells tested
      positive for acetylation only in the external lysine residues of the histone
      tail. Our data are compatible with an active TH gene expression in a 50% cell
      fraction of BE(2)-C-16 cells. Further analysis of epigenetic programming might
      lead to the identification of the factors that determine TH gene expression
      specifically in dopaminergic neurons.

PMID- 17195155
TI  - Selected excitation for CAS-SDCI calculations.
AB  - A new selected-configuration interaction method is proposed, based on the use of
      local orbitals. A corresponding code has been written, which is devoted to CI
      calculations of rather large systems (about 50-100 carbon-like atoms). Taking
      advantage of the locality, and then of the fact that interactions vanish when the
      distance is large, the dimension of the CI space is largely reduced. The
      determinants that would be created by long range excitations are expected to have
      a small weight in the wave function and are therefore eliminated. This selected
      excitation CI space is particularly suited for large molecules. It is tested on
      large polyene chains and on a transition metal complex. For large enough systems,
      the CPU time saving is important and, what is more noticeable, calculations that
      were impossible to perform without selection are feasible in this approach.

PMID- 17195156
TI  - Computational alanine scanning mutagenesis--an improved methodological approach.
AB  - Alanine scanning mutagenesis of protein-protein interfacial residues can be
      applied to a wide variety of protein complexes to understand the structural and
      energetic characteristics of the hot-spots. Binding free energies have been
      estimated with reasonable accuracy with empirical methods, such as Molecular
      Mechanics/Poisson-Boltzmann surface area (MM-PBSA), and with more rigorous
      computational approaches like Free Energy Perturbation (FEP) and Thermodynamic
      Integration (TI). The main objective of this work is the development of an
      improved methodological approach, with less computational cost, that predicts
      accurately differences in binding free energies between the wild-type and alanine
      mutated complexes (DeltaDeltaG(binding)). The method was applied to three
      complexes, and a mean unsigned error of 0.80 kcal/mol was obtained in a set of 46
      mutations. The computational method presented here achieved an overall success
      rate of 80% and an 82% success rate in residues for which alanine mutation causes
      an increase in the binding free energy > 2.0 kcal/mol (warm- and hot-spots). This
      fully atomistic computational methodological approach consists in a computational
      Molecular Dynamics simulation protocol performed in a continuum medium using the
      Generalized Born model. A set of three different internal dielectric constants,
      to mimic the different degree of relaxation of the interface when different types
      of amino acids are mutated for alanine, have to be used for the proteins,
      depending on the type of amino acid that is mutated. This method permits a
      systematic scanning mutagenesis of protein-protein interfaces and it is capable
      of anticipating the experimental results of mutagenesis, thus guiding new
      experimental investigations.

PMID- 17195157
TI  - Implementation and application of helix-helix distance and crossing angle
      restraint potentials.
AB  - Based on the definition of helix-helix distance and crossing angle introduced by
      Chothia et al. (J Mol Biol 1981, 145, 215), we have developed the restraint
      potentials by which the distance and crossing angle of two selected helices can
      be maintained around target values during molecular dynamics simulations. A
      series of assessments show that calculated restraint forces are numerically
      accurate. Since the restraint forces are only exerted on atoms which define the
      helical principal axes, each helix can rotate along its helical axis, depending
      on the helix-helix intermolecular interactions. Such a restraint potential
      enables us to characterize the helix-helix interactions at atomic details by
      sampling their conformational space around specific distance and crossing angle
      with (restraint) force-dependent fluctuations. Its efficacy is illustrated by
      calculating the potential of mean force as a function of helix-helix distance
      between two transmembrane helical peptides in an implicit membrane model.

PMID- 17195158
TI  - Collisions of ideal gas molecules with a rough/fractal surface. A computational
      study.
AB  - The frequency of collisions of ideal gas molecules (argon) with a rough surface
      has been studied. The rough/fractal surface was created using random deposition
      technique. By applying various depositions, the roughness of the surface was
      controlled and, as a measure of the irregularity, the fractal dimensions of the
      surfaces were determined. The surfaces were next immersed in argon (under
      pressures 2 x 10(3) to 2 x 10(5) Pa) and the numbers of collisions with these
      surfaces were counted. The calculations were carried out using a simplified
      molecular dynamics simulation technique (only hard core repulsions were assumed).
      As a result, it was stated that the frequency of collisions is a linear function
      of pressure for all fractal dimensions studied (D = 2, ..., 2.5). The frequency
      per unit pressure is quite complex function of the fractal dimension; however,
      the changes of that frequency with the fractal dimension are not strong. It was
      found that the frequency of collisions is controlled by the number of weakly
      folded sites on the surfaces and there is some mapping between the shape of
      adsorption energy distribution functions and this number of weakly folded sites.
      The results for the rough/fractal surfaces were compared with the prediction
      given by the Langmuir-Hertz equation (valid for smooth surface), generally the
      departure from the Langmuir-Hertz equation is not higher than 48% for the studied
      systems (i.e. for the surfaces created using the random deposition technique).

PMID- 17195159
TI  - Efficient combination of Wang-Landau and transition matrix Monte Carlo methods
      for protein simulations.
AB  - An efficient combination of the Wang-Landau and transition matrix Monte Carlo
      methods for protein and peptide simulations is described. At the initial stage of
      simulation the algorithm behaves like the Wang-Landau algorithm, allowing to
      sample the entire interval of energies, and at the later stages, it behaves like
      transition matrix Monte Carlo method and has significantly lower statistical
      errors. This combination allows to achieve fast convergence to the correct values
      of density of states. We propose that the violation of TTT identities may serve
      as a qualitative criterion to check the convergence of density of states. The
      simulation process can be parallelized by cutting the entire interval of
      simulation into subintervals. The violation of ergodicity in this case is
      discussed. We test the algorithm on a set of peptides of different lengths and
      observe good statistical convergent properties for the density of states. We
      believe that the method is of general nature and can be used for simulations of
      other systems with either discrete or continuous energy spectrum.

PMID- 17195160
TI  - Modifying the OPLS-AA force field to improve hydration free energies for several
      amino acid side chains using new atomic charges and an off-plane charge model for
      aromatic residues.
AB  - The hydration free energies of amino acid side chains are an important
      determinant of processes that involve partitioning between different
      environments, including protein folding, protein complex formation, and protein
      membrane interactions. Several recent papers have shown that calculated hydration
      free energies for polar and aromatic residues (Trp, His, Tyr, Asn, Gln, Asp, Glu)
      in several common molecular dynamics force fields differ significantly from
      experimentally measured values. We have attempted to improve the hydration
      energies for these residues by modifying the partial charges of the OPLS-AA force
      field based on natural population analysis of density functional theory
      calculations. The resulting differences between calculated hydration free
      energies and experimental results for the seven side chain analogs are less than
      0.1 kcal/mol. Simulations of the synthetic Trp-rich peptide Trpzip2 show that the
      new charges lead to significantly improved geometries for interacting Trp-side
      chains. We also investigated an off-plane charge model for aromatic rings that
      more closely mimics their electronic configuration. This model results in an
      improved free energy of hydration for Trp and a somewhat altered benzene-sodium
      potential of mean force with a more favorable energy for direct benzene-sodium
      contact.

PMID- 17195161
TI  - Effects of entropy on the gas-phase pyrolysis of ethyl N,N-dimethylcarbamate.
AB  - In this study, we examined the gas-phase pyrolysis of ethyl N,N-dimethylcarbamate
      theoretically at various theoretical levels. The reaction consists of a two-step
      mechanism, with N,N-dimethylcarbamic acid and ethylene as reaction intermediates.
      In the first step, the reaction proceeds via a six-membered cyclic transition
      state (TS), which is more favorable than that via a four-membered cyclic TS.
      Here, the contribution of entropy to the overall potential energy surface was
      found to play an important role in determining the rate-limiting step, which was
      found to be the second step when viewed in terms of the enthalpy of activation
      (DeltaH(not equal)), but the first step when entropy changes (-TDeltaS(not
      equal)) were considered. These results are consistent with experimental findings.
      Moreover, the experimental activation entropy can be reproduced by using the
      hindered rotor approximation, which converts some low vibration frequencies that
      correspond to internal rotational modes into hindered rotors.

PMID- 17195162
TI  - Electronic structures and chemical bonding in diatomic ScX to ZnX (X = S, Se,
      Te).
AB  - Bond distances, vibrational frequencies, electron affinities, ionization
      potentials, dissociation energies, and dipole moments of the title molecules in
      neutral, positively, and negatively charged ions were studied using density
      functional method. Ground electronic state was assigned for each molecule. The
      bonding patterns were analyzed and compared with both the available data and
      across the series. It was found that, besides ionic component, covalent bonds are
      formed between the metal s, d orbitals, and the p orbital of S, Se, and Te. For
      neutral and cationic molecules, the covalent character increases from ScX to CrX
      and from FeX to CuX with an exception of decrease at MnX and ZnX, while for
      anionic molecules, the trend is not obvious. For both neutral and charged
      molecules, the sulfides have the shortest bond distance and largest vibrational
      frequency, while tellurides have the largest bond distance and smallest
      vibrational frequency. For neutral and anionic molecules, the dissociation energy
      of sulfides is the largest, that of tellurides is the smallest, while this only
      remains true for cationic molecules from ScX(+) to FeX(+).

PMID- 17195163
TI  - Neglect of four- and approximation of one-, two-, and three-center two-electron
      integrals in a symmetrically orthogonalized basis.
AB  - A new integral approximation for use in molecular electronic structure
      calculations is proposed as an alternative to the traditional neglect of diatomic
      differential overlap models. The similarity between the symmetrically
      orthogonalized and the original basis functions (assumed orthonormal within each
      atomic set but nonorthogonal between different centers) is used to construct a
      robust approximation for the two-electron integrals, with the error being
      quadratic in the deviation between the products of the functions. Invariance
      properties of this procedure are rigorously proved. Numerical studies on a
      representative set of molecules at valence-only minimal basis Hartree-Fock level
      show that the approximation introduces relatively small errors, encouraging its
      future application in the semiempirical field.

PMID- 17195164
TI  - RPGR mutation analysis and disease: an update.
AB  - Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene are the most
      common single cause of retinitis pigmentosa, accounting for up to 15 to 20% of
      cases in Caucasians. A total of 240 different RPGR mutations have been reported,
      including 24 novel ones in this work, which are associated with X-linked
      retinitis pigmentosa (XLRP) (95%), cone, cone-rod dystrophy, or atrophic macular
      atrophy (3%), and syndromal retinal dystrophies with ciliary dyskinesia and
      hearing loss (2%). All disease-causing mutations occur in one or more RPGR
      isoforms containing the carboxyl-terminal exon open reading frame 15 (ORF15),
      which are widely expressed but show their highest expression in the connecting
      cilia of rod and cone photoreceptors. Of reported RPGR mutations, 55% occur in a
      glutamic acid-rich domain within exon ORF15, which accounts for only 31% of the
      protein. RPGR forms complexes with a variety of other proteins and appears to
      have a role in microtubular organization and transport between photoreceptor
      inner and outer segments.

PMID- 17195165
TI  - Bayesian parallel imaging with edge-preserving priors.
AB  - Existing parallel MRI methods are limited by a fundamental trade-off in that
      suppressing noise introduces aliasing artifacts. Bayesian methods with an
      appropriately chosen image prior offer a promising alternative; however, previous
      methods with spatial priors assume that intensities vary smoothly over the entire
      image, resulting in blurred edges. Here we introduce an edge-preserving prior
      (EPP) that instead assumes that intensities are piecewise smooth, and propose a
      new approach to efficiently compute its Bayesian estimate. The estimation task is
      formulated as an optimization problem that requires a nonconvex objective
      function to be minimized in a space with thousands of dimensions. As a result,
      traditional continuous minimization methods cannot be applied. This optimization
      task is closely related to some problems in the field of computer vision for
      which discrete optimization methods have been developed in the last few years. We
      adapt these algorithms, which are based on graph cuts, to address our
      optimization problem. The results of several parallel imaging experiments on
      brain and torso regions performed under challenging conditions with high
      acceleration factors are shown and compared with the results of conventional
      sensitivity encoding (SENSE) methods. An empirical analysis indicates that the
      proposed method visually improves overall quality compared to conventional
      methods.

PMID- 17195167
TI  - Molecular mechanisms involved in self-renewal and pluripotency of embryonic stem
      cells.
AB  - Embryonic stem cells (ES cells) are derived from inner cell mass (ICM). The self
      renewal and pluripotency are the main specificities of ES cells, which are likely
      to reveal a deeper understanding of human cellular biology and which are
      considered to be promising sources for cell therapy to treat patients with
      degenerative diseases in clinical. Growth of ES cells as a pluripotent population
      requires a balance between survival, proliferation, and self-renewal signals. In
      fact, the precise mechanism that regulates stem cell self-renewal and
      pluripotency remains largely unknown. Recently, in vitro and in vivo studies have
      identified several genetic regulators that may play important roles in the self
      renewal and pluripotency process of human and mouse ES cells, including
      extracellular signaling factors, transcription factors, cell-cycle regulators,
      microRNA, genes implicated in chromosomal stability, and DNA methylation. In this
      review, we will summarize the currently known molecular regulators for ES cells
      self-renewal, and we will propose some possibilities to explain the ways in which
      these distinct pathways might interact.

PMID- 17195166
TI  - Time-resolved 3D quantitative flow MRI of the major intracranial vessels: initial
      experience and comparative evaluation at 1.5T and 3.0T in combination with
      parallel imaging.
AB  - Exact knowledge of blood flow characteristics in the major cerebral vessels is of
      great relevance for diagnosing cerebrovascular abnormalities. This involves the
      assessment of hemodynamically critical areas as well as the derivation of
      biomechanical parameters such as wall shear stress and pressure gradients. A time
      resolved, 3D phase-contrast (PC) MRI method using parallel imaging was
      implemented to measure blood flow in three dimensions at multiple instances over
      the cardiac cycle. The 4D velocity data obtained from 14 healthy volunteers were
      used to investigate dynamic blood flow with the use of multiplanar reformatting,
      3D streamlines, and 4D particle tracing. In addition, the effects of magnetic
      field strength, parallel imaging, and temporal resolution on the data were
      investigated in a comparative evaluation at 1.5T and 3T using three different
      parallel imaging reduction factors and three different temporal resolutions in
      eight of the 14 subjects. Studies were consistently performed faster at 3T than
      at 1.5T because of better parallel imaging performance. A high temporal
      resolution (65 ms) was required to follow dynamic processes in the intracranial
      vessels. The 4D flow measurements provided a high degree of vascular conspicuity.
      Time-resolved streamline analysis provided features that have not been reported
      previously for the intracranial vasculature.

PMID- 17195168
TI  - Quantitative sensory testing of cold and vibration perception during compression
      of median nerve at the wrist.
AB  - We conducted a sequential study of quantitative sensory testing (QST) during
      compression-induced conduction block of the median nerve to determine relative
      vulnerability of the small and large myelinated nerve fibers. We tested cold
      (CPT) and vibratory perception thresholds (VPT) of the third digit in 15 healthy
      subjects during constant, localized compression for 30 min of the median nerve at
      the wrist. The orthodromic sensory nerve action potentials (SNAPs) recorded at
      wrist and elbow served to monitor the degree of associated conduction block.
      After the onset of nerve compression, it took 16 min for CPT to show the first
      change; VPT remained normal for 26 min. CPT recovered 2 min later than VPT after
      release of compression. The SNAP amplitude at the wrist diminished immediately at
      the start of compression and declined progressively, whereas the response at the
      elbow remained the same initially, showing no latency change for 20 min. A nearly
      identical time course of SNAP changes in the two experiments justified the
      comparison of separately tested CPT and VPT as a measure of modality-specific
      vulnerability. Contrary to the common belief, a focal compression sufficient to
      produce rapidly reversible conduction abnormalities affects the slow-conducting
      small myelinated fibers mediating cold perception before the fast-conducting
      large myelinated fibers transmitting vibration perception. The data document the
      order of modality-specific vulnerability of sensory nerve fibers to mild
      compression. The finding suggests that testing CPT, rather than VPT, provides a
      better QST to delineate rapidly reversible symptoms induced by compression.

PMID- 17195169
TI  - Does motoneuron adaptation contribute to muscle fatigue?
AB  - To help reduce the gap between the cellular physiology of motoneurons (MNs) as
      studied "bottom-up" in animal preparations and the "top-down" study of the firing
      patterns of human motor units (MUs), this article addresses the question of
      whether motoneuron adaptation contributes to muscle fatigue. Findings are
      reviewed on the intracellularly recorded electrophysiology of spinal MNs as
      studied in vivo and in vitro using animal preparations, and the extracellularly
      recorded discharge of MUs as studied in conscious humans. The latter "top-down"
      approach, combined with kinetic measurements, has provided most of what is
      currently known about the neurobiology of muscle fatigue, including its task and
      context dependencies. It is argued that although the question addressed is still
      open, it should now be possible to design new "bottom-up" research paradigms
      using animal preparations that take advantage of what has been learned with the
      use of relatively noninvasive quantitative procedures in conscious humans.

PMID- 17195170
TI  - Effect of tumor necrosis factor alpha on electrically induced calcium transients
      elicited in C2C12 skeletal myotubes.
AB  - Diseases involving chronic inflammation can lead to prolonged exposure of
      skeletal muscle to inflammatory cytokines such as tumor necrosis factor alpha
      (TNFalpha), which may contribute to the skeletal muscle weakness seen in these
      conditions. In this study we examined the effect of a prolonged exposure to
      TNFalpha on intracellular Ca(2+) transients elicited in skeletal C(2)C(12)
      myotubes. A 48-h exposure to TNFalpha (10 ng/mL) significantly reduced the peaks,
      time to peak, and rate of Ca(2+) decay of electrically induced Ca(2+) transients
      elicited in C(2)C(12) skeletal myotubes. TNFalpha exposure had no significant
      effect on the resting Ca(2+) levels. The results of this study indicate that
      prolonged exposure to TNFalpha decreases sarcoplasmic reticulum Ca(2+) release in
      cultured skeletal muscle cells. This altered Ca(2+) release could contribute to
      the muscle weakness found in conditions involving chronic inflammation.

PMID- 17195171
TI  - Uremic neuropathy: clinical features and new pathophysiological insights.
AB  - Neuropathy is a common complication of end-stage kidney disease (ESKD), typically
      presenting as a distal symmetrical process with greater lower-limb than upper
      limb involvement. The condition is of insidious onset, progressing over months.
      and has been estimated to be present in 60%-100% of patients on dialysis.
      Neuropathy generally only develops at glomerular filtration rates of less than 12
      ml/min. The most frequent clinical features reflect large-fiber involvement, with
      paresthesias, reduction in deep tendon reflexes, impaired vibration sense, muscle
      wasting, and weakness. Nerve conduction studies demonstrate findings consistent
      with a generalized neuropathy of the axonal type. Patients may also develop
      autonomic features, with postural hypotension, impaired sweating, diarrhea,
      constipation, or impotence. The development of uremic neuropathy has been related
      previously to the retention of neurotoxic molecules in the middle molecular
      range, although this hypothesis lacked formal proof. Studies utilizing novel
      axonal excitability techniques have recently shed further light on the
      pathophysiology of this condition. Nerves of uremic patients have been shown to
      exist in a chronically depolarized state prior to dialysis, with subsequent
      improvement and normalization of resting membrane potential after dialysis. The
      degree of depolarization correlates with serum K(+), suggesting that chronic
      hyperkalemic depolarization plays an important role in the development of nerve
      dysfunction in ESKD. These recent findings suggest that maintenance of serum K(+)
      within normal limits between periods of dialysis, rather than simple avoidance of
      hyperkalemia, is likely to reduce the incidence and severity of uremic
      neuropathy.

PMID- 17195172
TI  - Decisions for extent of gastric surgery in gastric cancer patients: younger
      patients require more attention than the elderly.
AB  - BACKGROUND AND OBJECTIVES: There is a prevailing belief that young patients with
      gastric adenocarcinomas have a more aggressive disease. METHODS: We reviewed the
      prospectively collected database of 753 gastric adenocarcinomas patients who had
      undergone curative gastrectomy. Clinicopathological factors and the survival
      rates for each pathological TNM stage were compared between patients younger than
      40 years of age and the others. RESULTS: Fifty-four (9.8%) patients were younger
      than 40 years of age. The overall accuracy of the intra-operative stage was
      62.5%; 54.0% in the young patients and 63.5% in older patients (P = 0.006).
      Intraoperative under-staging was more commonly seen in the younger patients when
      compared to the older patients. These trends were more prominent in patients with
      surgical stage I disease. Age proved to be an independent risk factor influencing
      the accuracy of intraoperative staging using a logistic regression analysis.
      There was no difference in overall 3-year survival rate between the two age
      groups for each pathological TNM stage. CONCLUSIONS: The present study showed
      that intra-operative under-staging was more common in young patients with gastric
      cancer, especially with stage I disease. This finding raises the concern for
      inaccurate diagnosis and surgical under treatment in younger patients with stage
      I gastric cancer.

PMID- 17195176
TI  - Levator ani trigger point injections: An underutilized treatment for chronic
      pelvic pain.
AB  - AIMS: We conducted this study to examine the role of trigger point injections in
      females with chronic pelvic pain (CPP) of at least 6 months duration and specific
      levator ani trigger points. METHODS: This prospective study included 18
      consecutive female patients with CPP and specific palpable levator ani trigger
      points. Pain was evaluated before and after trigger point injection on a Visual
      Analog Scale (VAS). Patient global satisfaction (PGS) and cure rates (PGC) were
      also measured by a VAS on a scale of 0-100%. The trigger points were identified
      manually by intravaginal palpation of the levator ani bilaterally. A mixture of
      10 cc of 0.25% bupivacaine, 10 cc of 2% lidocaine and 1 cc (40 mg) of
      triamcinolone was used for injection of 5 cc per trigger point. A 5.5'' Iowa
      trumpet pudendal needle guide was used for injection. All but one injection were
      performed in the office setting without sedation. Pelvic floor muscle exercises
      were taught for use after injection. Success was defined as a decrease in pain as
      measured by a VAS of 50% or more, as well as PGS and PGC scores of 60% or
      greater. There was a mean follow up of 3 months after trigger point injection.
      RESULTS: Thirteen of 18 women improved with the first trigger point injection
      resulting in a comprehensive success rate of 72%. Six (33%) of 18 women were
      completely pain free. CONCLUSION: In the management of CPP, a non-surgical office
      based therapy such as trigger point injections can be effective in selected
      patients.

PMID- 17195180
TI  - SOST expression is restricted to the great arteries during embryonic and neonatal
      cardiovascular development.
AB  - Spatial-temporal regulation of bone morphogenetic protein (BMP) and Wnt activity
      is essential for normal cardiovascular development, and altered activity of these
      growth factors causes maldevelopment of the cardiac outflow tract and great
      arteries. In the present study, we show that SOST, a Dan family member reported
      to antagonize BMP and Wnt activity, is expressed within the medial vessel wall of
      the great arteries containing smooth muscle cells. The ascending aorta, aortic
      arch, brachiocephalic artery, common carotids, and pulmonary trunk were all
      associated with SOST expressing smooth muscle cells, while the heart itself,
      including the valves, and more distal arteries, that is, pulmonary arteries,
      subclavian arteries, and descending aorta, were negative. SOST was expressed from
      embryonic day 15.5 up to the neonatal period. SOST expression, however, did not
      correspond with inhibition of Smad-dependent BMP activity or beta-catenin
      dependent Wnt activity in the great arteries. Activity of both signaling pathways
      was already down-regulated before induction of SOST expression.

PMID- 17195179
TI  - Rho kinase inhibitor Y27632 affects initial heart myofibrillogenesis in cultured
      chick blastoderm.
AB  - During early vertebrate development, Rho-associated kinases (ROCKs) are involved
      in various developmental processes. Here, we investigated spatiotemporal
      expression patterns of ROCK1 protein and examined the role of ROCK during initial
      heart myofibrillogenesis in cultured chick blastoderm. Immunohistochemistry
      showed that ROCK1 protein was distributed in migrating mesendoderm cells,
      visceral mesoderm of the pericardial coelom (from which cardiomyocytes will later
      develop), and cardiomyocytes of the primitive heart tube. Pharmacological
      inhibition of ROCK by Y27632 did not alter the myocardial specification process
      in cultured posterior blastoderm. However, Y27632 disturbed the formation of
      striated heart myofibrils in cultured posterior blastoderm. Furthermore, Y27632
      affected the formation of costamere, a vinculin/integrin-based rib-like cell
      adhesion site. In such cardiomyocytes, cell-cell adhesion was disrupted and N
      cadherin was distributed in the perinuclear region. Pharmacological inactivation
      of myosin light chain kinase, a downstream of ROCK, by ML-9 perturbed the
      formation of striated myofibrils as well as costameres, but not cell-cell
      adhesion. These results suggest that ROCK plays a role in the formation of
      initial heart myofibrillogenesis by means of actin-myosin assembly, and focal
      adhesion/costamere and cell-cell adhesion.

PMID- 17195181
TI  - Expression of TM4SF10, a Claudin/EMP/PMP22 family cell junction protein, during
      mouse kidney development and podocyte differentiation.
AB  - Cell junctions in the nephron are highly specialized to perform specific and
      distinct filtration and reabsorption functions. The mature kidney forms complex
      cell junctions including slit diaphragms that prevent the passage of serum
      proteins into the filtrate, and tubule cell junctions that regulate specific
      paracellular ion reuptake. We have investigated the expression of TM4SF10 (Trans
      Membrane tetra(4)-Span Family 10) in mouse kidneys. TM4SF10 is the vertebrate
      orthologue of Caenorhabditis elegans VAB-9, a tetraspan adherens junction protein
      in the PMP22/EMP/Claudin family of proteins. We found that TM4SF10 localizes at
      the basal-most region of podocyte precursors before the capillary loop stage, at
      some tubule precursors, and at the ureteric bud junction with S-shaped bodies.
      Overall expression of TM4SF10 peaked at postnatal day 4 and was virtually absent
      in adult kidneys. The very limited expression of TM4SF10 protein that persisted
      into adulthood was restricted to a few tubule segments but remained localized to
      the basal region of lateral membranes. In undifferentiated cultured podocytes,
      TM4SF10 localized to the perinuclear region and translocated to the cell membrane
      after Cadherin appearance at cell-cell contacts. TM4SF10 colocalized with ZO1 and
      p120ctn in undifferentiated confluent podocytes and also colocalized with the
      tips of actin filaments at cell contacts. Upon differentiation of cultured
      podocytes, TM4SF10 protein disappeared from cell contacts and expression ceased.
      These results suggest that TM4SF10 functions during differentiation of podocytes
      and may participate in the maturation of cell junctions from simple adherens
      junctions to elaborate slit diaphragms. TM4SF10 may define a new class of Claudin
      like proteins that function during junctional development.

PMID- 17195182
TI  - Combinatorial expression patterns of heparan sulfate sulfotransferases in
      zebrafish: III. 2-O-sulfotransferase and C5-epimerases.
AB  - Heparan sulfate (HS) is an unbranched chain of repetitive disaccharides, which
      specifically binds ligands when attached to the cell surface or secreted
      extracellularly. HS chains contain sulfated domains, termed the HS fine
      structure, which give HS specific binding affinities for extracellular ligands.
      HS 2-O-sulfotransferase (2-OST) catalyzes the transfer of sulfate groups to the 2
      O position of uronic acid residues of HS. We report here the characterization and
      developmental expression patterns of 2-OST in several tissues/organs throughout
      early zebrafish development, including early cleavage stages, eyes, somites,
      brain, internal organ primordial, and pectoral fin. The 2-OST gene has spatially
      and temporally distinct expression, which is a surprise given the essential role
      of 2-OST in HS fine structure formation. Furthermore, although 2-OST and C5
      epimerase are predicted to be interdependent for protein translocation from the
      endoplasmic reticulum to the Golgi, their expression is not coordinately
      regulated during zebrafish development.

PMID- 17195184
TI  - Initial specification of the epibranchial placode in zebrafish embryos depends on
      the fibroblast growth factor signal.
AB  - In vertebrates, cranial sensory ganglia are mainly derived from ectodermal
      placodes, which are focal thickenings at characteristic positions in the
      embryonic head. Here, we provide the first description of the early development
      of the epibranchial placode in zebrafish embryos using sox3 as a molecular
      marker. By the one-somite stage, we saw a pair of single sox3-expressing domains
      appear lateral to the future hindbrain. The sox3 domain, which is referred to
      here as the early lateral placode, is segregated during the early phase of
      segmentation to form a pax2a-positive medial area and a pax2a-negative lateral
      area. The medial area subsequently developed to form the otic placode, while the
      lateral area was further segregated along the anteroposterior axis, giving rise
      to four sox3-positive subdomains by 26 hr postfertilization. Given their spatial
      relationship with the expression of the markers for the epibranchial ganglion, as
      well as their positions and temporal changes, we propose that these four domains
      correspond to the facial, glossopharyngeal, vagal, and posterior lateral line
      placodes in an anterior-to-posterior order. The expression of sox3 in the early
      lateral placode was absent in mutants lacking functional fgf8, while implantation
      of fibroblast growth factor (FGF) beads restored the sox3 expression. Using
      SU5402, which inhibits the FGF signal, we were able to demonstrate that formation
      of both the early lateral domains and later epibranchial placodes depends on the
      FGF signal operating at the beginning of somitogenesis. Together, these data
      provide evidence for the essential role of FGF signals in the development of the
      epibranchial placodes.

PMID- 17195185
TI  - Treatment of pulmonary fibrosis in systemic sclerosis: light at the end of the
      tunnel?

PMID- 17195186
TI  - Outcomes after switching from one anti-tumor necrosis factor alpha agent to a
      second anti-tumor necrosis factor alpha agent in patients with rheumatoid
      arthritis: results from a large UK national cohort study.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) who experience treatment
      failure with one anti-tumor necrosis factor (anti-TNF) agent, due to either
      inefficacy or toxicity, are frequently switched to a second anti-TNF agent,
      although the benefits of switching are unknown. The present study was undertaken
      to compare drug continuation rates between the first course and second course of
      anti-TNF therapy. METHODS: The study involved a prospective cohort of RA patients
      from a UK national register of new anti-TNF treatment starts (n = 6,739; 876
      starting adalimumab, 2,826 starting etanercept, and starting 3,037 infliximab).
      Over a mean 15 months of followup, 841 patients stopped taking the first drug due
      to inefficacy and 1,023 stopped the first drug due to toxicity, of whom 503 and
      353, respectively, were switched to a second anti-TNF agent. Kaplan-Meier
      survival curves were plotted to determine continuation rates for each course, and
      Cox regression was used to compare each course for the risk of stopping and the
      reason for stopping (inefficacy or toxicity). RESULTS: Overall, 73% of patients
      who switched to a second anti-TNF agent remained on the new therapy by the end of
      followup. First drug discontinuation due to inefficacy was associated with an
      increased rate of second drug discontinuation due to inefficacy (hazard ratio
      [HR] 2.7, 95% confidence interval [95% CI] 2.1-3.4) but not toxicity (HR 1.1, 95%
      CI 0.9-1.5). Similarly, first drug discontinuation due to toxicity was associated
      with an increased rate of second drug discontinuation due to toxicity (HR 2.3,
      95% CI 1.9-2.9) but not inefficacy (HR 1.2, 95% CI 0.8-1.6). CONCLUSION: RA
      patients who are switched to a second anti-TNF drug have high rates of
      continuation, although among those who must discontinue treatment, the reasons
      for stopping a second drug are related to the reasons for stopping the first
      drug. This large data set from the UK provides the first estimates of the
      magnitude of these effects in patients with long-standing severe RA.

PMID- 17195187
TI  - Genetically determined high serum levels of mannose-binding lectin and
      agalactosyl IgG are associated with ischemic heart disease in rheumatoid
      arthritis.
AB  - OBJECTIVE: Patients with rheumatoid arthritis (RA) have excess morbidity and
      mortality due to ischemic heart disease. It has been suggested that high serum
      levels of mannose-binding lectin (MBL) and agalactosyl IgG (IgG-G0) are
      associated with increased inflammation in RA. MBL also enhances inflammation
      mediated tissue injury during postischemic reperfusion. This study was undertaken
      to examine whether these factors are associated with increased risk of ischemic
      heart disease in RA. METHODS: MBL alleles were genotyped in 229 Danish patients
      with RA. In addition, serum levels of MBL and IgG-G0 were measured. Incidences of
      ischemic heart disease, myocardial infarction, and death due to ischemic heart
      disease after the diagnosis of RA were assessed in a prospective study. RESULTS:
      During a median followup of 9.5 years, ischemic heart disease was diagnosed in 8
      of 27 patients with genetically determined high serum levels of MBL, as compared
      with 24 of the remaining 192 patients (data not available on 10 patients). After
      correction for other known risk factors, the hazard ratio (HR) was 3.6 (95%
      confidence interval [95% CI] 1.4-9.2). The corrected HR for myocardial infarction
      was 9.0 (95% CI 2.2-36.4). High serum levels of MBL also conferred an increased
      risk of death due to ischemic heart disease (age- and sex-adjusted HR 10.5, 95%
      CI 2.7-41.3). However, further analyses showed that these associations were
      present only in patients with high serum levels of IgG-G0. CONCLUSION:
      Genetically determined high serum levels of MBL and high serum levels of IgG-G0
      are associated with increased risk of ischemic heart disease, myocardial
      infarction, and premature death in patients with RA.

PMID- 17195188
TI  - Comparison of the expression patterns of newly identified zebrafish retinoic acid
      and retinoid X receptors.
AB  - Retinoic acid (RA) signaling is important for multiple aspects of embryonic
      development and tissue homeostasis. Heterodimers of retinoic acid receptors
      (RARs) and retinoid X receptors (RXRs) transduce RA signaling. It is not yet
      clear how the diversity of receptor combinations relates to the diversity of
      functions for RA. The expression patterns of three zebrafish RARs and four RXRs
      were reported recently. Here, we identify an additional RAR, a zebrafish RARgamma
      paralog, and two additional RXRs, duplicates of the previously identified
      RXRalpha and RXRgamma. Thus, the zebrafish genome contains duplicates of each RAR
      and RXR gene. All zebrafish RAR and RXR paralogs have overlapping and distinct
      areas of expression, as might be expected for duplicate genes in the process of
      diverging in function. By representing what is potentially the complete set of
      zebrafish RARs and RXRs, this study provides a valuable reference for future
      functional studies of the individual zebrafish RARs and RXRs.

PMID- 17195189
TI  - Global growth deficiencies in mice lacking the ribosomal protein HIP/RPL29.
AB  - Because of their deleterious effects on developing organisms, ribosomal protein
      (RP) mutations have been poorly described in mammals, and only a few heterozygous
      mutations have been shown to be viable. This observation is believed to be due to
      the fact that each RP is an essential component in the assembly of a functional
      stable ribosome. Here, we created gene targeted mutant mice lacking HIP/RPL29, an
      RP associated with translationally active ribosomes in eukaryotes. In contrast to
      other RP mutants, HIP/RPL29 null mice are viable but are up to 50% smaller than
      their control littermates at weaning age. In null embryos, delayed global growth
      is first observed around mid-gestation, and postnatal lethality due to low birth
      weight results in distortion of the Mendelian ratio. Prenatal growth defects are
      not fully compensated for during adulthood, and null animals display
      proportionately smaller organs and stature, and reach sexual maturity
      considerably later when compared with their control siblings. Additionally,
      HIP/RPL29 null embryonic fibroblasts have decreased rates of proliferation and
      protein synthesis and exhibit reduced steady state levels of core RPs.
      Altogether, our findings provide conclusive genetic evidence that HIP/RPL29
      functions as an important regulator of global growth by modulating the rate of
      protein synthesis.

PMID- 17195190
TI  - Sex and rheumatoid arthritis: mouse model versus human disease.

PMID- 17195191
TI  - Spondylarthritides and related entities: entheses and hypotheses.

PMID- 17195192
TI  - CO2-enhanced sonographically guided radiofrequency ablation and transcatheter
      arterial chemoembolization for small hepatocellular carcinoma poorly defined on
      conventional sonography.
AB  - We report a case of hepatocellular carcinoma located just below the right
      hemidiaphragm that was diagnosed as having hepatitis C virus-related cirrhosis 12
      years ago. Although the lesion was not clear on conventional sonography, it was
      clearly defined on CO(2)-enhanced sonography, allowing safe and accurate
      radiofrequency ablation. By combining radiofrequency ablation with transcatheter
      arterial chemoembolization, extensive cauterization and complete tumor necrosis
      were obtained with only 1 session of treatment. The patient had no serious
      adverse effects and has shown no recurrence during 35 months of follow-up.

PMID- 17195193
TI  - Postcircumcision necrosis of the glans penis: gray-scale and color Doppler
      sonographic findings.
AB  - We report the case of a 2-week-old male infant who developed necrosis of the
      glans penis as a result of circumcision. Based on the clinical absence of
      impairment of micturition on gray-scale and color Doppler sonographic findings,
      which showed the relatively superficial necrosis of the skin layers without
      underlying damage to the corpora cavernosa or urethra, a conservative approach
      was chosen with a good prognosis. A 4-month follow-up sonograpic examination
      revealed evidence of glans healing with superficial skin epithelization. These
      findings may lead to mild cosmetic damage, but no future functional complications
      are expected. To our knowledge, this is the first report of gray-scale and color
      Doppler sonographic evaluation of the ischemic process of the glans in a neonate
      with this rare complication of circumcision.

PMID- 17195194
TI  - One-year results of unprotected left main disease treatment with paclitaxel
      eluting stents: results of a multicenter registry.
AB  - BACKGROUND: Preliminary data suggest that drug-eluting stents might have a role
      in selected cases of unprotected left main stenosis (ULMS). The purpose of this
      study was to determine the rates of death, myocardial infarction, and repeated
      revascularization in a multicenter, prospective series of patients with ULMS
      treated with paclitaxel-eluting stents. METHODS: A prospective registry was
      initiated in March 2003 through December 2004 in five tertiary centers including
      all patients with a significant (>50%) stenosis in ULMS treated with at least one
      paclitaxel-eluting stent. There were no clinical or angiographic exclusion
      criteria. Clinical follow-up was obtained at 6 and 12 months. RESULTS: A total of
      100 patients were included. Mean age was 67.6 +/- 11.4 years and 36% were
      diabetics. Distal left main was affected in 53% of patients. Implantation of two
      stents was required in only 15%. Angiographic success was achieved in all cases.
      Significant periprocedural CK-MB elevation occurred in 5 patients and there was 1
      intraprocedural death. At a median 9 months follow-up, cardiac death occurred in
      7%, the majority of which (4%) in patients with ST-elevation myocardial
      infarction and cardiogenic shock before stent implantation. Only 3 patients (3%)
      required repeated target-vessel revascularization, all repeated angioplasty
      procedures. CONCLUSION: Percutaneous treatment of unprotected left main lesions
      with paclitaxel-eluting stents is associated with acceptable mid-term results in
      selected patients, with very low rates of repeated revascularization.

PMID- 17195195
TI  - Percutaneous septal ablation with absorbable gelatin sponge in hypertrophic
      obstructive cardiomyopathy.
AB  - The treatment of the hypertrophic obstructive cardiomyopathy (HOCM) by
      percutaneous transluminal septal myocardial ablation (PTSMA) with ethanol
      injection has greatly improved in the last years. This report describes the case
      of a patient with symptomatic drug-refractory HOCM who underwent an unsuccessful
      attempt to thrombose the septal artery by PTSMA with alcohol. It has therefore
      been decided to use small absorbant gelatin sponge (AGS) particles, obtaining
      immediate thrombotic occlusion of the artery and excellent hemodynamic results
      with immediate and permanent disappearance of the gradient. The patient
      progressed satisfactorily and displayed lower than average creatine kinase levels
      in comparison to the rest of our PTMSA patients. After 2 years of follow-up he
      still remains asymptomatic and without any gradient. These results suggest that
      PTSMA with AGS could be a valuable alternative treatment of HOCM.

PMID- 17195196
TI  - Clinical images: three-dimensional computed tomography imaging of tophaceous
      gout.

PMID- 17195197
TI  - Hemodynamic improvement is faster after percutaneous ASD closure than after
      surgery.
AB  - OBJECTIVES: Hemodynamic effects of surgical and percutaneous closure of atrial
      septal defect (ASD) were evaluated. BACKGROUND: ASD causes volume overload of
      right ventricle (RV) and is associated with distortion and dysfunction of left
      ventricle (LV). The amount and timing of hemodynamic changes after ASD closure
      are not well known. METHODS: The study group consisted of 7 children treated
      surgically and 17 treated in the catheterization laboratory. In the control
      group, there were 51 healthy children. RV size and LV end-diastolic and systolic
      dimensions, volumes, and function were examined by two- and three- dimensional
      echocardiography and serum concentrations of natriuretic peptides measured prior
      to ASD closure, and 1, 6, and 12 months thereafter. RESULTS: In all children with
      ASD, during the 1-year follow-up, the z score of RV end-diastolic diameter
      decreased from a median 5.00 SD to 2.25 SD (P < 0.001). Dilatation of RV did not
      resolve entirely during 1-year follow-up in either treatment group. End-diastolic
      LV diameter increased from -1.50 to -0.50 SD (P < 0.001). LV size increased
      slower in the surgical subgroup but reached control levels in both groups.
      Concentrations of natriuretic peptides increased during the first month after ASD
      closure and normalized thereafter in patients treated percutaneously but remained
      higher than in controls in patients treated surgically. CONCLUSIONS: During 1
      year follow-up after ASD closure, RV size decreases but does not normalize in all
      patients. The size of the LV normalizes after ASD closure but the increase in LV
      size is slower in patients treated surgically. Serum levels of ANPN and proBNP
      are elevated prior to ASD closure but decrease thereafter to control levels in
      patients treated with the percutaneous technique but not in those treated
      surgically.

PMID- 17195198
TI  - Successful nonsurgical treatment of left main stem perforation by sacrifice of
      the LAD.
AB  - We report two cases of coronary artery disease treated percutaneously and
      including rotational atherectomy, in which the interventional procedure was
      complicated by left main coronary artery perforation. The management and outcome
      of this potentially fatal complication are discussed.

PMID- 17195199
TI  - Incidence and clinical impact of coronary stent fracture after sirolimus-eluting
      stent implantation.
AB  - BACKGROUND: Stent fracture is one of the possible causes of restenosis after
      sirolimus-eluting stents (SES) implantation. The aim of our study was to evaluate
      the prevalence and clinical impact of coronary stent fracture after SES
      implantation. METHODS: From our prospective institutional database, 280 patients
      were treated solely with SES from August 2004 to June 2005. Among the 280
      patients, 256 patients with a total of 307 lesions underwent follow-up
      angiography on an average of 240 days after the procedure. RESULTS: Stent
      fractures were observed in eight (2.6%) lesions. Of the eight lesions with stent
      fracture, five were located in the right coronary artery (RCA), two in the
      saphenous vein (SV) graft, and one in the left anterior descending coronary
      artery. The stent fractures were all in the locations that served as hinges
      during vessel movement in the cardiac contraction cycle. Seven of the eight stent
      fractures were adjacent to the edge of previously implanted or overlapped stent.
      Significant multivariate predictors of stent fracture were SV graft location
      (Odds ratio 35.88; 95% confidence interval 2.73-471.6, P = 0.006), implanted
      stent length (Odds ratio 1.04; 95% confidence interval 1.01-1.07, P = 0.02), and
      RCA location (Odds ratio 10.00; 95% confidence interval 1.11-89.67, P = 0.04). In
      stent binary restenosis rate was 37.5% and target lesion repeat revascularization
      rate was 50.0% in patients with stent fracture. CONCLUSIONS: Stent fracture was
      likely to be affected by mechanical stress provoked by rigid structures and hinge
      points. Stent fracture might be associated with the high incidence of target
      lesion revascularization.

PMID- 17195200
TI  - Transcatheter closure of ischemic and post-traumatic ventricular septal ruptures.
AB  - Post-traumatic ventricular septal defects (VSD) can occur after acute MI or
      iatrogenically after invasive surgical procedures. Emergency surgery is
      associated with high perioperative mortality and postsurgical shunt in up to 20%
      of patients. Transcatheter closure (TCC) of post MI VSD may be an alternative
      that avoids the high risk of surgery. We report a lower mortality and morbidity
      than surgical closure in the post infarction VSD's even with a short interval
      between defect occurrence and percutaneous device placement. Furthermore, in
      patients with a failed or suboptimal surgical result adjunctive percutaneous
      closure may be beneficial and offers an alternative to redo VSD repair. Finally,
      in patients who suffer an unexpected traumatic VSD post surgical procedure,
      percutaneous closure offers an alternative with excellent results.

PMID- 17195202
TI  - Simultaneous kissing stent technique to treat left main stem bifurcation disease.
AB  - BACKGROUND: While several endovascular techniques have been developed for
      treating arterial bifurcation lesions, there is, as yet, no single, widely
      accepted technique for treating left main stem (LMS) bifurcation lesions with
      stents. The simultaneous kissing stent (SCS) technique seems particularly suited
      for such lesions. The authors describe a consecutive cohort of patients with LMS
      bifurcation stenosis treated with this technique and present mechanistic insights
      from a porcine model. METHODS: Thirty consecutive patients with LMS bifurcation
      stenosis +/- multivessel disease were treated with SCS technique using paclitaxel
      eluting stents. The technique involves simultaneous implantation of two stents
      (LMS-LAD and LMS-Cx) so that the proximal end of both stents lie at the same
      level in the body of LMS. Symptom status was recorded and follow-up angiography
      was performed. In addition, four pigs underwent SCS implantation of the LMS and
      were studied by direct examination, histology, and scanning electron microscopy.
      RESULTS: The patients' mean age was 63, 26 were elective and 19 were male.
      Paclitaxel-eluting stents (Taxus, Boston Scientific) were used. There was one in
      hospital death in a highly unstable patient. At 6-month follow-up angiography,
      two patients required target lesion revascularization. At 13 +/- 3 month follow
      up, the remaining patients remain well, with no other major adverse cardiac
      events. The animals all survived with patent stents. SEM demonstrated full re
      endothelialization and histology showed a thin but complete neointima covering
      the stent struts. CONCLUSION: The SCS technique for treating LMS bifurcation
      disease with paclitaxel-eluting stents is safe and feasible. Medium term clinical
      and angiographic results are good. An endothelium and a thin neointima cover the
      metal struts.

PMID- 17195203
TI  - Stent fracture associated with drug-eluting stents: clinical characteristics and
      implications.
AB  - OBJECTIVE: To evaluate the clinical characteristics and implications of stent
      fracture in drug-eluting stents. BACKGROUND: Approximately 2.5 million drug
      eluting stents are implanted every year worldwide. In 10 randomized controlled
      trials involving 2,602 patients, no incidence of stent fracture was recognized or
      reported. METHODS: From April 2003 to December 2005, 2,728 patients underwent
      drug-eluting stenting. The angiograms of all 530 patients who underwent repeat
      angiography were analyzed to identify the presence of stent fracture. We then
      documented the incidence of adverse events associated with drug-eluting stent
      fracture and systematically analyzed the clinical, procedural, and structural
      factors, which might predispose to stent fracture. RESULTS: Stent fracture was
      identified in 10 patients. None of these fractures were detectable at the time of
      stent placement. The median time interval from stent implantation to detection of
      fracture at repeat angiography was 226 days (range, 7-620 days). Adverse clinical
      outcomes associated with stent fracture occurred in 7 patients (6 patients had
      binary restenosis and 1 patient had stent thrombosis), all necessitating repeat
      intervention. Analysis of potential predisposing clinical, procedural, and
      structural factors revealed that 4 patients had excessive tortuosity in the
      proximal segment, and overlapping stents were used in 5 cases. All fractures
      occurred in sirolimus-eluting stents. CONCLUSIONS: Stent fracture may represent a
      new potential mechanism of restenosis and stent thrombosis in drug-eluting
      stents. Predisposing clinical and procedural factors may be vessel tortuosity and
      use of overlapping stents. The most important predisposing factor, however, may
      be stent structure, since all fractures occurred in sirolimus-eluting stents.

PMID- 17195204
TI  - Inferior infarction following alcohol septal ablation: a consequence of
      "collateral damage"?
AB  - Alcohol septal ablation is fast becoming the most common method to reduce left
      ventricular outflow tract gradient in patients with symptomatic hypertrophic
      obstructive cardiomyopathy. Myocardial contrast echocardiography (MCE) is
      routinely used as an adjunct to avoid the spread of alcohol to non-target areas
      of myocardium. We report two cases where despite the careful use of MCE, remote
      inferior wall myocardial infarctions occurred. The likely mechanism and possible
      preventive measures are discussed.

PMID- 17195205
TI  - Effectiveness and safety of the sirolimus-eluting stents coated with
      bioabsorbable polymer coating in human coronary arteries.
AB  - BACKGROUND: Although the sirolimus-eluting stent (CYPHER, Cordis, USA) has shown
      a dramatic reduction of restenosis, there are still some concerns about its
      efficacy and safety. Its durable polymer coating may enhance neointimal
      proliferation and residual sirolimus, which cannot be released from polymer, may
      result in incomplete reendothelization. As a drug reservoir, bioabsorbable
      polymer (polylactic acid, PLA) is more rational. OBJECTIVE: We aimed to determine
      the safety and efficacy of sirolimus-eluting stent coated with PLA (EXCEL, JW
      Medical Systems, China) in the treatment of human coronary arterial diseases.
      METHODS: The study included 31 patients with de novo coronary lesions, with
      vessels 2.5-3.5 mm in diameter. The primary end points included the percentage of
      in-stent restenosis of the luminal diameter and in-stent late luminal loss at 6
      months, as determined by quantitative angiography. The secondary end point was
      the major adverse cardiac events (MACE) 30 days and 6 months after the index
      procedure. RESULTS: Forty-eight EXCEL stents were successfully delivered in the
      34 lesions, and multiple stents were implanted in 35.3% of lesions. All patients
      were discharged without clinical complications and completed clinical follow-up
      at 1 and 6 months. No MACE had occurred. Twenty patients (30 stents) completed 6
      months of angiographic follow-up. No in-stent or in-lesion restenosis (diameter
      stenosis > or =50%) was observed. In-stent late loss was (0.07 +/- 0.17) mm.
      CONCLUSIONS: The implantation of EXCEL stent is feasible and safe and elicits
      minimal neointimal proliferation. This new stent has potential advantages
      regarding the long-long-term result over the commercially stent as the new stent
      has no sustained stimulation to the local tissue.

PMID- 17195206
TI  - Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme
      and rheumatoid arthritis in the Japanese population.
AB  - OBJECTIVE: Analyses of families with rheumatoid arthritis (RA) have suggested the
      presence of a putative susceptibility locus on chromosome 14q21-23. This large
      population-based genetic association study was undertaken to examine this region.
      METHODS: A 2-stage case-control association study of 950 unrelated Japanese
      patients with RA and 950 healthy controls was performed using >400 gene-based
      common single-nucleotide polymorphisms (SNPs). RESULTS: Multiple SNPs in the
      PRKCH gene encoding the eta isozyme of protein kinase C (PKCeta) showed
      significant single-locus disease associations, the most significant being SNP
      c.427+8134C>T (odds ratio 0.72, 95% confidence interval 0.62-0.83, P = 5.9 x 10(
      5)). Each RA-associated SNP was consistently mapped to 3 distinct regions of
      strong linkage disequilibrium (i.e., linkage disequilibrium or haplotype blocks)
      in the PRKCH gene locus, suggesting that multiple causal variants influence
      disease susceptibility. Significant SNPs included a novel common missense
      polymorphism of the PRKCH gene, V374I (rs2230500), which lies within the ATP
      binding site that is highly conserved among PKC superfamily members. In
      circulating lymphocytes, PRKCH messenger RNA was expressed at higher levels in
      resting T cells (CD4(+) or CD8(+)) than in B cells (CD19(+)) or monocytes
      (CD14(+)) and was significantly down-regulated through immune responses.
      CONCLUSION: Our results provide evidence of the involvement of PRKCH as a
      susceptibility gene for RA in the Japanese population. Dysregulation of PKCeta
      signal transduction pathway(s) may confer increased risk of RA through aberrant T
      cell-mediated autoimmune responses.

PMID- 17195207
TI  - CD56-expressing T cells that have features of senescence are expanded in
      rheumatoid arthritis.
AB  - OBJECTIVE: T cells deficient in CD28 expression have been implicated in the
      pathogenesis of rheumatoid arthritis (RA). Given that CD28-null T cells are
      functionally heterogeneous, we undertook this study to screen for novel receptors
      on these cells. METHODS: Seventy-two patients with RA (ages 35-84 years) and 53
      healthy persons (32 young controls ages 19-34 years, 21 older controls ages 39-86
      years) were recruited. Phenotypes and proliferative capacity of T cells from
      fresh leukocytes and of long-term cultures were monitored by flow cytometry. Lung
      biopsy specimens from patients with RA-associated interstitial pneumonitis (IP)
      were examined by immunohistochemistry. Receptor functionality was assessed by
      crosslinking bioassays. RESULTS: Chronic stimulation of CD28(+) T cells in vitro
      yielded progenies that lacked CD28 but that gained CD56. Ex vivo analysis of
      leukocytes from patients with extraarticular RA showed a higher frequency of
      CD56(+),CD28-null T cells than in patients with disease confined to the joints or
      in healthy controls. CD56(+),CD28-null T cells had nil capacity for
      proliferation, consistent with cellular senescence. CD56(+) T cells had skewed T
      cell receptor (TCR) alpha/beta-chain usage and restricted TCR third
      complementarity-determining region spectra. Histologic studies showed that
      CD56(+) T cells were components of cellular infiltrates in RA-associated IP. CD56
      crosslinking on T cells sufficiently induced cytokine production, although
      CD56/TCR coligation induced higher production levels. CONCLUSION: Chronic
      activation of T cells induces counterregulation of CD28 and CD56 expression. The
      loss of CD28 is accompanied by the gain of CD56 that confers TCR-independent and
      TCR-dependent activation pathways. We propose that accumulation of CD56(+) T
      cells in RA contributes to maladaptive immune responses and that CD56(+) T cells
      are potential targets for therapy.

PMID- 17195208
TI  - Dissecting the heterogeneity of rheumatoid arthritis through linkage analysis of
      quantitative traits.
AB  - OBJECTIVE: To dissect the heterogeneity of rheumatoid arthritis (RA) through
      linkage analysis of quantitative traits, specifically, IgM rheumatoid factor (IgM
      RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibody titers.
      METHODS: Subjects, 1,002 RA patients from 491 multiplex families recruited by the
      North American RA Consortium, were typed for 379 microsatellite markers. Anti-CCP
      titers were determined based on a second-generation enzyme-linked immunosorbent
      assay, and IgM-RF levels were quantified by immunonephelometry. We used the
      Merlin statistical package to perform nonparametric quantitative trait linkage
      analysis. RESULTS: For each of the quantitative traits, evidence of linkage, with
      logarithm of odds (LOD) scores of >1.0, was found in 9 regions. For both traits,
      the strongest evidence of linkage was for marker D6S1629 on chromosome 6p (LOD
      14.02 for anti-CCP and LOD 12.09 for RF). Six other regions with LOD scores of
      >1.0 overlapped between the 2 traits, on chromosomes 1p21.1, 5q15, 8p23.1,
      16p12.1, 16q23.1, and 18q21.31. Evidence of linkage to anti-CCP titer but not to
      RF titer was found in 2 regions (chromosomes 9p21.3 and 10q21.1), and evidence of
      linkage to RF titer but not to anti-CCP titer was found in 2 regions (chromosomes
      5p15.2 and 1q42.3). Several covariates were significantly associated with 1 or
      both traits, and linkage analysis exploring the covariate effects revealed
      striking effects of sex in modulating linkage signals for several chromosomal
      regions. For example, sex had a striking impact on the linkage results for both
      quantitative traits on chromosome 6p (P = 0.0007 for anti-CCP titer and P =
      0.0012 for RF titer), suggesting a sex-HLA region interaction. CONCLUSION:
      Analysis of quantitative components of RA is a promising approach for dissecting
      the genetic heterogeneity of this complex disorder. These results highlight the
      potential importance of sex or other covariates that may modulate some of the
      genetic effects that influence the risk of specific disease manifestations.

PMID- 17195210
TI  - Tenosynovitis and osteoclast formation as the initial preclinical changes in a
      murine model of inflammatory arthritis.
AB  - OBJECTIVE: To determine the nature of the initial changes of joint inflammation
      occurring before, at the time of, and shortly after onset of clinically apparent
      arthritis. METHODS: Human tumor necrosis factor (TNF)-transgenic mice were
      assessed for clinical, histologic, immunophenotypic, serologic, and molecular
      changes at the preclinical phase of arthritis, at the onset of disease, and at
      the stage of early clinical disease. In addition, the effects of a genetic
      osteoclast deficiency and pharmacologic inhibition of TNF were studied in these
      initial phases of disease. RESULTS: Initial articular changes were observed even
      before the start of clinical symptoms. Infiltration of the tendon sheaths by
      granulocytes and macrophages as well as formation of osteoclasts next to the
      inflamed tendon sheaths were the first pathologic events. Tenosynovitis rapidly
      led to remodeling of the sheaths into pannus-like tissue, which formed
      osteoclasts that invaded the adjacent mineralized cartilage. Early lesions were
      associated with up-regulation of interleukin-1 (IL-1) and IL-6 as well as
      activation of p38 MAPK and ERK. In contrast, absence of osteoclasts led to
      uncoupling of tenosynovitis from invasion into cartilage and bone. TNF blockade
      also attenuated the pathologic changes associated with tenosynovitis. CONCLUSION:
      Structural damage begins even before the onset of clinical symptoms of arthritis
      and involves the tendon sheaths as well as adjacent cartilage and bone. These
      results suggest that tenosynovitis is an initiating feature of arthritis and that
      joint destruction starts right from the onset of disease. Our findings thus
      underscore the importance of immediate initiation of an effective therapy in
      patients with rheumatoid arthritis.

PMID- 17195212
TI  - Evaluation of protease-activated receptor 2 in murine models of arthritis.
AB  - OBJECTIVE: Protease-activated receptor 2 (PAR-2) activation has been linked to
      pro- and antiinflammatory cellular responses. We undertook this study to explore
      the importance of PAR-2 activation in 4 murine models of arthritis and to analyze
      the expression of PAR-2 in human arthritic synovium. METHODS: Zymosan-induced
      arthritis (ZIA), K/BxN serum-induced arthritis, and Freund's complete adjuvant
      (CFA)-induced arthritis were generated in naive PAR-2(-/-) mice and PAR-2(+/+)
      littermates. Antigen-induced arthritis (AIA) was generated in immunized mice
      using methylated bovine serum albumin (mBSA). The severity of arthritis was
      assessed by clinical scoring, technetium uptake measurement, and histologic
      analysis. Immune responses to mBSA were also evaluated from AIA. The expression
      of PAR-2 in synovial tissues from rheumatoid arthritis (RA) and osteoarthritis
      (OA) patients was compared. RESULTS: In AIA, arthritis was significantly
      decreased in PAR-2-deficient mice and was associated with decreased levels of
      anti-mBSA IgG antibodies and lymph node cell proliferation. No difference in
      arthritis severity was seen in mice with ZIA, K/BxN serum-induced arthritis, and
      CFA-induced arthritis. Synovial biopsy specimens from RA patients demonstrated
      significantly increased expression of PAR-2 compared with those from OA patients.
      CONCLUSION: PAR-2 deficiency was found to modulate articular inflammation in
      murine models of arthritis that require prior immunization and was associated
      with reduced levels of anti-mBSA IgG and lymph node cell proliferation in AIA.
      Expression of PAR-2 in RA synovium was significantly higher than that in OA
      synovium, and this suggests that PAR-2 is implicated in the pathogenesis of
      immune-mediated forms of arthritis.

PMID- 17195209
TI  - New humanized HLA-DR4-transgenic mice that mimic the sex bias of rheumatoid
      arthritis.
AB  - OBJECTIVE: To generate a mouse model that can mimic human rheumatoid arthritis
      (RA). A major difference between RA in humans and collagen-induced arthritis
      (CIA) in mice is the lack of sex bias and autoantibodies in the animal model. We
      used DRB1*0401-transgenic mice to understand the role of DR4 in susceptibility
      and sex bias in RA. METHODS: A transgenic mouse was generated that lacked all
      endogenous mouse class II genes (AE(o)) and expressed the RA susceptibility
      allele HLA-DRB1*0401. These transgenic mice were tested for incidence, severity,
      and sex distribution of CIA. RESULTS: DRB1*0401.AE(o) mice developed CIA
      predominantly in females and produced rheumatoid factors, similar to the features
      of human RA. Another feature similar to human RA is the expression of class II
      molecules on antigen-presenting cells as well as T cells. Activated and sorted
      CD4(+) T cells can present DR4-restricted type II collagen (CII)-derived peptide
      in vitro, but cannot process the antigen. This suggests a role for these cells in
      epitope presentation locally in joints, which affects disease severity. After
      challenge with CII, female mice had higher cellularity and increased T cell
      proliferation and produced higher levels of proinflammatory cytokines than did
      the male mice. CONCLUSION: DR4.AE(o) mice expressed HLA similar to humans and
      displayed increased arthritis susceptibility in females, thus mimicking RA in
      humans. This model may be valuable for studying sex differences observed in
      humans and for understanding why autoimmunity is increased in women. These mice
      may also be useful for developing future therapeutic strategies.

PMID- 17195211
TI  - Interleukin-17 as a molecular target in immune-mediated arthritis:
      immunoregulatory properties of genetically modified murine dendritic cells that
      secrete interleukin-4.
AB  - OBJECTIVE: Our previous studies have shown that murine dendritic cells (DCs)
      genetically modified to express interleukin-4 (IL-4) reduce the incidence and
      severity of murine collagen-induced arthritis. The present studies were performed
      to assess the immunoregulatory mechanisms underlying this response, by assessing
      the effects of IL-4 DCs on cytokine production by subsets of T helper cells.
      METHODS: Male DBA mice ages 6-8 weeks old were immunized with type II collagen.
      Splenic T cells obtained during the initiation phase and the end stage of
      arthritis were cultured with IL-4 DCs or untransduced DCs in the presence of
      collagen rechallenge. Interferon-gamma (IFNgamma) and IL-17 responses were
      measured. Antibodies to IL-4, IL-12, and IL-23, and recombinant IL-4, IL-12, and
      IL-23 were used to further study the regulation of T cell cytokine production by
      IL-4 DCs. RESULTS: Splenic T cells obtained during the initiation phase of
      arthritis produced less IL-17 when cultured in the presence of IL-4 DCs, despite
      their production of increased quantities of other proinflammatory cytokines
      (IFNgamma and tumor necrosis factor). T cell IL-17 production after collagen
      rechallenge was not inhibited by a lack of IL-23, since IL-4-mediated suppression
      of IL-17 was not reconstituted by IL-23, an otherwise potent inducer of IL-17
      production by T cells. Although IL-4 DCs can produce increased quantities of IL
      12 and IFNgamma, suppression of IL-17 production by IL-4 DCs was independent of
      both. While IL-17 production by T cells obtained during the initiation phase of
      arthritis was regulated by IL-4 DCs, IL-17 production by T cells obtained during
      end-stage arthritis was not altered. CONCLUSION: Our data suggest that IL-4 DCs
      exert a therapeutic effect on collagen-induced arthritis by targeting IL-17. IL
      17 suppression by IL-4 DCs is robust and is not reversed by IL-23. Timing might
      be important in IL-17-targeted therapy, since IL-17 production by T cells
      obtained during end-stage arthritis did not respond to suppression by IL-4 DCs.

PMID- 17195213
TI  - Reduced expression and proteolytic susceptibility of lubricin/superficial zone
      protein may explain early elevation in the coefficient of friction in the joints
      of rats with antigen-induced arthritis.
AB  - OBJECTIVE: To investigate the effect of arthritis development and progression on
      the integrity and function of lubricin and the relationship of lubricin to
      cartilage damage in a rat antigen-induced arthritis model. METHODS: Arthritis was
      induced in the right knee joints, using methylated bovine serum albumin and
      Freund's complete adjuvant. Whole joint friction measurements were performed ex
      vivo with a modified Stanton pendulum configuration, and coefficients of friction
      (mu) were determined. Levels of messenger RNA (mRNA) for lubricin, cathepsin B,
      and interleukin-1beta (IL-1beta) in synovial tissue from control and affected
      joints were determined by quantitative polymerase chain reaction. Lubricin
      staining in cartilage was performed using a lubricin-specific monoclonal
      antibody. RESULTS: The mu values in excised right joints following arthritis
      induction were significantly (P < 0.001) higher than those in excised left
      joints. Lubricin mRNA expression levels in synovial tissue on days 4 and 7 after
      arthritis induction were significantly (P < 0.001) lower in the right joints
      compared with the left joints, whereas levels of cathepsin B and IL-1beta mRNA
      expression on days 4, 7, and 14 were significantly (P < 0.001) higher in the
      right joints than the left joints. Lubricin staining was diminished in cartilage
      from the right joints compared with the left joints. CONCLUSION: Elevated
      coefficients of friction in arthritic joints occur concurrently with enhanced
      proteolytic degradation by up-regulated cathepsin B and other proteases, as well
      as decreased lubricin synthesis by synovial fibroblasts and superficial zone
      chondrocytes. Loss of joint lubrication is an early event in inflammatory
      arthropathy. Restoring chondroprotection and preventing potential wear-induced
      cartilage degradation may require lubricin supplementation in synovial fluid.

PMID- 17195214
TI  - Use of molecular imaging to quantify response to IKK-2 inhibitor treatment in
      murine arthritis.
AB  - OBJECTIVE: The NF-kappaB signaling pathway promotes the immune response in
      rheumatoid arthritis (RA) and in rodent models of RA. NF-kappaB activity is
      regulated by the IKK-2 kinase during inflammatory responses. To elucidate how IKK
      2 inhibition suppresses disease development, we used a combination of in vivo
      imaging, transcription profiling, and histopathology technologies to study mice
      with antibody-induced arthritis. METHODS: ML120B, a potent, small molecule
      inhibitor of IKK-2, was administered to arthritic animals, and disease activity
      was monitored. NF-kappaB activity in diseased joints was quantified by in vivo
      imaging. Quantitative reverse transcriptase-polymerase chain reaction was used to
      evaluate gene expression in joints. Protease-activated near-infrared fluorescence
      (NIRF) in vivo imaging was applied to assess the amounts of active proteases in
      the joints. RESULTS: Oral administration of ML120B suppressed both clinical and
      histopathologic manifestations of disease. In vivo imaging demonstrated that NF
      kappaB activity in inflamed arthritic paws was inhibited by ML120B, resulting in
      significant suppression of multiple genes in the NF-kappaB pathway, i.e., KC,
      epithelial neutrophil-activating peptide 78, JE, intercellular adhesion molecule
      1, CD3, CD68, tumor necrosis factor alpha, interleukin-1beta, interleukin-6,
      inducible nitric oxide synthase, cyclooxygenase 2, matrix metalloproteinase 3,
      cathepsin B, and cathepsin K. NIRF in vivo imaging demonstrated that ML120B
      treatment dramatically reduced the amount of active proteases in the joints.
      CONCLUSION: Our data demonstrate that IKK-2 inhibition in the murine model of
      antibody-induced arthritis suppresses both inflammation and joint destruction. In
      addition, this study highlights how gene expression profiling can facilitate the
      identification of surrogate biomarkers of disease activity and treatment response
      in an experimental model of arthritis.

PMID- 17195215
TI  - Low levels of vitamin D and worsening of knee osteoarthritis: results of two
      longitudinal studies.
AB  - OBJECTIVE: To confirm reports that 25-hydroxyvitamin D (25[OH]D) deficiency is
      associated with an increased risk of joint space narrowing or cartilage loss in
      osteoarthritis (OA). METHODS: We measured 25(OH)D levels in subjects from 2
      longitudinal cohort studies, the Framingham Osteoarthritis Study and the Boston
      Osteoarthritis of the Knee Study (BOKS). In the first, weight-bearing
      anteroposterior (AP) and lateral knee radiographs were obtained on subjects in
      1993-1994 and again in 2002-2005 (mean interval 9 years); blood was drawn for
      measurement of vitamin D status in 1996-2000. In the second, subjects with
      symptomatic knee OA participating in a natural history study had fluoroscopically
      positioned semiflexed posteroanterior (PA) and lateral radiography of both knees
      and magnetic resonance imaging (MRI) of the more symptomatic knee performed at
      baseline and at 15 and 30 months. Blood was drawn at all visits, and the baseline
      specimen was used when available. In both studies, we defined radiographic
      worsening based on joint space loss in the tibiofemoral joint on either AP/PA or
      lateral weight-bearing views, using a semiquantitative scale (worsening defined
      as increase by > or =1 on a 0-3 scale). In the BOKS, we evaluated cartilage loss
      semiquantitatively, using the Whole-Organ Magnetic Resonance Imaging Score. In
      both studies, 25(OH)D levels were measured by radioimmunoassay. Analyses focused
      on whether vitamin D levels, defined in tertiles or as deficient (25[OH]D <20
      ng/ml) versus nondeficient, predicted worsening of OA. Logistic regression
      analysis adjusted for age, body mass index, sex, and baseline OA level was used.
      RESULTS: The 715 subjects in the Framingham Study had a mean 25(OH)D level of 20
      ng/ml at baseline, and 20.3% of the knees showed worsening, during the course of
      the study, with most knees having had no evidence of OA at baseline. The 277
      subjects with OA in the BOKS had a mean 25(OH)D level of 20 ng/ml at baseline
      with 23.6% of knees showing radiographic worsening. We found no association of
      baseline 25(OH)D levels with radiographic worsening in either cohort, and
      confidence limits in the analyses of vitamin D deficiency were narrow, suggesting
      that results were not based on insufficient power. In fact, the risk of worsening
      was slightly, but not significantly, lower in persons with low levels of vitamin
      D than in persons with higher levels. In the BOKS, vitamin D levels were
      unrelated to cartilage loss seen on MRI. CONCLUSION: The findings indicate that
      vitamin D status is unrelated to the risk of joint space or cartilage loss in
      knee OA.

PMID- 17195216
TI  - Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and
      FRZB with genetic susceptibility to osteoarthritis of the knee.
AB  - OBJECTIVE: To assess whether the association of genetic polymorphisms with
      osteoarthritis (OA) in other populations could be replicated in a large,
      multicenter, mixed-sex, case-control study of clinical knee OA. METHODS: Genetic
      polymorphisms in OA candidate genes were genotyped in 298 men and 305 women, ages
      50-86 years, all of whom had a diagnosis of knee OA as assessed clinically and
      radiographically, and in 300 male and 299 female control subjects matched for age
      and ethnicity. Allele and haplotype frequencies for 5 genes (ASPN, CALM1, COL2A1,
      COMP, and FRZB) previously tested for association with hip and/or knee OA in
      other populations were compared between patients and control subjects, analyzing
      men and women separately. RESULTS: The same FRZB 2-marker single-nucleotide
      polymorphism (SNP) haplotype associated with hip OA in other populations of
      Caucasian women was shown to increase the risk of knee OA among the women (but
      not the men) in the current study (odds ratio [OR] 2.87, P < 0.04). The CALM1
      SNP, which affects the risk of hip OA in Japanese individuals, was not shown to
      be associated with susceptibility to OA in men or women. COL2A1 haplotypes were
      demonstrated to be associated with a decreased risk of knee OA in men (OR 0.68, P
      < 0.005) but not in women. COMP haplotypes that were associated with
      susceptibility to knee OA were different in men and women (P < 0.014 and P <
      0.032, respectively). A meta-analysis of these data and those from previously
      published reports indicated a strong association between the FRZB G324 allele (P
      < 0.0003) and suggested that an ASPN allele is protective against the risk of
      knee OA in Caucasians (P < 0.02). CONCLUSION: Our results indicate that genetic
      polymorphisms affecting knee OA vary between populations (Japanese versus
      Caucasian) and sexes and indicate a role for ASPN, COMP, FRZB, and COL2A1 in
      Caucasians.

PMID- 17195217
TI  - Crucial role of macrophages in matrix metalloproteinase-mediated cartilage
      destruction during experimental osteoarthritis: involvement of matrix
      metalloproteinase 3.
AB  - OBJECTIVE: To explore the involvement of synovial macrophages in early cartilage
      damage in osteoarthritis (OA), and to identify the role of matrix
      metalloproteinase 3 (MMP-3) in the pathology of early and late OA. METHODS: The
      role of synovial macrophages in MMP-mediated damage in OA was studied by
      depleting synovial macrophages prior to elicitation of a collagenase-induced
      instability model of OA. The expression of MMP in synovium and cartilage was
      monitored using TaqMan analysis. In spontaneous and induced OA, cartilage
      pathology was scored in MMP-3-knockout mice and control mice, by histologic
      assessment and VDIPEN staining. RESULTS: On day 14 following induction of OA, MMP
      mediated neoepitopes were detected in cartilage from mice with mild experimental
      OA (mean +/- SD positively stained surface area 20 +/- 3.2%). Remarkably, by
      depleting synovial macrophages prior to induction of OA, the generation of MMP
      induced neoepitopes was largely prevented (mean +/- SD positively stained surface
      area 5 +/- 1%; P< 0.001), indicating an important role for synovial macrophages
      in the occurrence of MMP-mediated cartilage damage. We observed a strong decrease
      in MMP-3 and MMP-9 expression in synovial but not cartilage tissue in macrophage
      depleted joints. Among 2-year-old mice, spontaneous OA-like changes in the lining
      layer were significantly decreased in MMP-3-knockout mice compared with control
      mice. Even more striking was the 67% reduction in the occurrence of severe
      cartilage damage in MMP-3-knockout mice. In addition, MMP-mediated VDIPEN
      expression was significantly decreased, indicating reduced MMP-mediated cartilage
      breakdown. CONCLUSION: The results of this study prove that MMP-3 is involved in
      the generation of severe cartilage damage in murine OA. Synovial macrophages are
      crucial in early MMP activity and appear to mediate MMP production in synovium
      rather than cartilage.

PMID- 17195219
TI  - Isolation and chondroinduction of a dermis-isolated, aggrecan-sensitive
      subpopulation with high chondrogenic potential.
AB  - OBJECTIVE: To develop a process that yields tissue-engineered articular cartilage
      constructs from skin-derived cells. METHODS: Dermis-isolated, aggrecan-sensitive
      (DIAS) cells were isolated using a modified rapid adherence process. The
      chondrogenic potential was measured by quantitative reverse transcriptase
      polymerase chain reaction, enzyme-linked immunosorbent assay, and
      immunohistochemistry. Filamentous actin (F-actin) and vinculin organization was
      detected using fluorescence microscopy. RESULTS: The rapid adherence process led
      to a selection of DIAS cells, <10% of the entire population. DIAS cells displayed
      greater chondroinduction potential, as evidenced by the formation of large
      numbers of chondrocytic nodules on aggrecan-coated surfaces. In addition, these
      cells showed higher gene expression and protein production in terms of
      chondrocytic markers when compared with unpurified dermis cells. Similar patterns
      of F-actin and vinculin organization were observed between DIAS cells and
      chondrocytes. Three-dimensional constructs from chondroinduced DIAS cells
      produced greater amounts of cartilage matrix than constructs from the rest of the
      dermis populations. CONCLUSION: These findings show a series of steps that work
      together to form tissue-engineered articular cartilage constructs using DIAS
      cells. Since skin presents a minimally invasive, relatively abundant cell source
      for tissue engineering, this study offers evidence of an efficient and stable
      technique to form cartilage constructs for future cartilage regeneration with
      autologous cells from skin.

PMID- 17195218
TI  - Restoration of the extracellular matrix in human osteoarthritic articular
      cartilage by overexpression of the transcription factor SOX9.
AB  - OBJECTIVE: Human osteoarthritis (OA) is characterized by a pathologic shift in
      articular cartilage homeostasis toward the progressive loss of extracellular
      matrix (ECM). The purpose of this study was to investigate the ability of rAAV
      mediated SOX9 overexpression to restore major ECM components in human OA
      articular cartilage. METHODS: We monitored the synthesis and content of
      proteoglycans and type II collagen in 3-dimensional cultures of human normal and
      OA articular chondrocytes and in explant cultures of human normal and OA
      articular cartilage following direct application of a recombinant adeno
      associated virus (rAAV) SOX9 vector in vitro and in situ. We also analyzed the
      effects of this treatment on cell proliferation in these systems. RESULTS:
      Following SOX9 gene transfer, expression levels of proteoglycans and type II
      collagen increased over time in normal and OA articular chondrocytes in vitro. In
      situ, overexpression of SOX9 in normal and OA articular cartilage stimulated
      proteoglycan and type II collagen synthesis in a dose-dependent manner. These
      effects were not associated with changes in chondrocyte proliferation. Notably,
      expression of the 2 principal matrix components could be restored in OA articular
      cartilage to levels similar to those in normal cartilage. CONCLUSION: These data
      support the concept of using direct, rAAV-mediated transfer of chondrogenic genes
      to articular cartilage for the treatment of OA in humans.

PMID- 17195220
TI  - Three-dimensional cartilage tissue engineering using adult stem cells from
      osteoarthritis patients.
AB  - OBJECTIVE: To determine whether it is possible to engineer 3-dimensional hyaline
      cartilage using mesenchymal stem cells derived from the bone marrow (BMSCs) of
      patients with osteoarthritis (OA). METHODS: Expanded BMSCs derived from patients
      with hip OA were seeded onto polyglycolic acid scaffolds and differentiated using
      transforming growth factor beta3 in the presence or absence of parathyroid
      hormone-related protein (PTHrP) to regulate hypertrophy. Micromass pellet
      cultures were established using the same cells for comparison. At the end of
      culture, the constructs or pellets were processed for messenger RNA (mRNA)
      analysis by quantitative real-time reverse transcription-polymerase chain
      reaction. Matrix proteins were analyzed using specific assays. RESULTS: Cartilage
      constructs engineered from BMSCs were at least 5 times the weight of equivalent
      pellet cultures. Histologic, mRNA, and biochemical analyses of the constructs
      showed extensive synthesis of proteoglycan and type II collagen but only low
      levels of type I collagen. The protein content was almost identical to that of
      cartilage engineered from bovine nasal chondrocytes. Analysis of type X collagen
      mRNA revealed a high level of mRNA in chondrogenic constructs compared with that
      in undifferentiated BMSCs, indicating an increased risk of hypertrophy in the
      tissue-engineered cells. However, the inclusion of PTHrP at a dose of 1 microM or
      10 microM during the culture period resulted in significant suppression of type X
      collagen mRNA expression and a significant decrease in alkaline phosphatase
      activity, without any loss of the cartilage-specific matrix proteins. CONCLUSION:
      Three-dimensional hyaline cartilage can be engineered using BMSCs from patients
      with OA. This method could thus be used for the repair of cartilage lesions.

PMID- 17195222
TI  - Exposure of human cartilage tissue to low concentrations of blood for a short
      period of time leads to prolonged cartilage damage: an in vitro study.
AB  - OBJECTIVE: Joint bleeding, or hemarthrosis, leads in time to severe joint damage.
      This study was carried out to test the in vitro thresholds of exposure time and
      concentration that lead to irreversible joint damage, to add to the discussion on
      the usefulness of aspiration of the joint after a hemorrhage. METHODS: Explants
      of healthy human articular cartilage tissue were cultured in the presence or
      absence of 50% (volume/volume) blood for 1, 2, 3, or 4 days or in the presence of
      0%, 5%, 10%, 20%, 30%, or 50% (v/v) blood for 4 days, followed by a 12-day period
      of recovery after withdrawal of blood. The effect of blood exposure on cartilage
      was determined by measuring the rate of proteoglycan synthesis as well as the
      release and content of cartilage matrix proteoglycans and the activity of matrix
      metalloproteinases. RESULTS: Exposure of cartilage to 50% (v/v) blood led to
      adverse changes that were largely independent of the exposure time. The adverse
      effects persisted after an initial exposure of up to or exceeding 2 days.
      Exposure of cartilage to increasing concentrations of blood for 4 days led to
      concentration-dependent adverse changes. These effects persisted when the
      concentration equaled or exceeded 10% (v/v) blood. Moreover, after 2 days of
      exposure to a blood load of 10% (v/v), the adverse effects on cartilage were not
      reversible. CONCLUSION: A 2-day exposure of cartilage in vitro to 10% (v/v) blood
      leads to prolonged impairment of joint cartilage. This suggests that aspiration
      of blood from the joint within 2 days after hemarthrosis should be considered to
      prevent blood-induced joint damage in the long term.

PMID- 17195221
TI  - Mechanisms of cartilage growth: modulation of balance between proteoglycan and
      collagen in vitro using chondroitinase ABC.
AB  - OBJECTIVE: To examine the cartilage growth-associated effects of a disruption in
      the balance between the swelling pressure of glycosaminoglycans (GAGs) and the
      restraining function of the collagen network, by diminishing GAG content prior to
      culture using enzymatic treatment with chondroitinase ABC. METHODS: Immature
      bovine articular cartilage explants from the superficial and middle layers were
      analyzed immediately or after incubation in serum-supplemented medium for 13
      days. Other explants were treated with chondroitinase ABC to deplete tissue GAG
      and also either analyzed immediately or after incubation in serum-supplemented
      medium for 13 days. Treatment- and incubation-associated variations in tissue
      volume, contents of proteoglycan and collagen network components, and tensile
      mechanical properties were assessed. RESULTS: Incubation in serum-supplemented
      medium resulted in expansive growth with a marked increase in tissue volume that
      was associated with a diminution of tensile integrity. In contrast,
      chondroitinase ABC treatment on day 0 led to a marked reduction of GAG content
      and enhancement of tensile integrity, and subsequent incubation led to
      maturational growth with minimal changes in tissue volume and maintenance of
      tensile integrity at the enhanced levels. CONCLUSION: The data demonstrate that a
      manipulation of GAG content in articular cartilage explants can distinctly alter
      the growth phenotype of cartilage. This may have practical utility for tissue
      engineering and cartilage repair. For example, the expansive growth phenotype may
      be useful to fill cartilage defects, while the maturational growth phenotype may
      be useful to induce matrix stabilization after filling defect spaces.

PMID- 17195223
TI  - Fracture risk with intermittent high-dose oral glucocorticoid therapy.
AB  - OBJECTIVE: To evaluate the risk of fracture in patients receiving intermittent
      therapy with high-dose oral glucocorticoids (GCs). METHODS: The study group
      comprised 191,752 patients from the UK General Practice Database who were 40
      years of age and older and received therapy with GCs. The followup time period
      was divided into the categories of "current" and "no exposure." The daily dose
      and cumulative dose for each time period were determined. Relative risks were
      estimated using Cox proportional hazards models, adjusted for age, sex, body mass
      index, smoking, disease history, and drug history. Fractures of the radius/ulna,
      humerus, rib, femur/hip, pelvis, or vertebrae were included in the evaluation.
      RESULTS: Patients who intermittently received high-dose GCs (daily dose > or =15
      mg) and had no or little previous exposure to GCs (cumulative exposure < or =1
      gm) had a small increased risk of osteoporotic (but not hip/femur) fracture; this
      risk increased substantially with increasing cumulative exposure. Among patients
      who received a daily dose > or =30 mg and whose cumulative exposure was >5 gm,
      the relative risk (RR) of osteoporotic fracture was 3.63 (95% confidence interval
      [95% CI] 2.54-5.20), the RR of fracture of the hip/femur was 3.13 (95% CI 1.49
      6.59), and the RR of vertebral fracture was 14.42 (95% CI 8.29-25.08).
      CONCLUSION: Intermittent use of high-dose oral GCs (daily dose > or =15 mg and
      cumulative exposure < or =1 gm) may result in a small increased risk of
      osteoporotic fracture. Conversely, patients who receive several courses of high
      dose GCs (daily dose > or =15 mg and cumulative exposure >1 gm) have a
      substantially increased risk of fracture.

PMID- 17195224
TI  - Clinical images: visualization of the inner synovial surface with three
      dimensional ultrasonography.

PMID- 17195225
TI  - HLA-B27 up-regulation causes accumulation of misfolded heavy chains and
      correlates with the magnitude of the unfolded protein response in transgenic
      rats: Implications for the pathogenesis of spondylarthritis-like disease.
AB  - OBJECTIVE: HLA-B27 is implicated in the pathogenesis of spondylarthritis (SpA),
      yet the molecular mechanisms are incompletely defined. HLA-B27 misfolding has
      been associated with endoplasmic reticulum stress and activation of the unfolded
      protein response (UPR) in macrophages from HLA-B27/human beta(2)-microglobulin
      transgenic (B27-transgenic) rats. This study was performed to assess the
      mechanisms that drive activation of the HLA-B27-induced UPR and to determine
      whether splenocytes respond in a similar manner. METHODS: Splenocytes were
      isolated and bone marrow macrophages were derived from B27-transgenic and wild
      type rats. Cells were treated for up to 24 hours with cytokines that induce class
      I major histocompatibility complex expression. HLA-B27 expression and misfolding
      were assessed by real-time reverse transcription-polymerase chain reaction, flow
      cytometry, and immunoblotting. Activation of the UPR was measured by quantifying
      UPR target gene expression and X-box binding protein 1 messenger RNA (mRNA)
      splicing. RESULTS: HLA-B27 mRNA up-regulation was accompanied by a dramatic
      increase in the accumulation of misfolded heavy chains and preceded robust
      activation of the UPR in macrophages. When macrophages were treated with various
      cytokines, the magnitude of the UPR correlated strongly with the degree of HLA
      B27 up-regulation. In contrast, B27-transgenic splenocytes exhibited only low
      level differences in the expression of UPR target genes after exposure to
      interferon-gamma or concanavalin A, which resulted in minimal HLA-B27 up
      regulation. CONCLUSION: These results suggest that HLA-B27-associated activation
      of the UPR in macrophages is attributable to the accumulation of misfolded heavy
      chains, and that certain cell types may be more susceptible to the effects of HLA
      B27 misfolding. Strategies that eliminate HLA-B27 up-regulation and/or the
      accumulation of misfolded heavy chains may be useful in evaluating the role of
      these events in the pathogenesis of SpA.

PMID- 17195226
TI  - Microdamage and altered vascularity at the enthesis-bone interface provides an
      anatomic explanation for bone involvement in the HLA-B27-associated
      spondylarthritides and allied disorders.
AB  - OBJECTIVE: To describe the basis for entheseal-associated bone disease in the
      spondylarthritides, by analyzing microanatomic and histopathologic relationships
      between soft tissue, bone cortex, and adjacent trabeculae. METHODS: Serial
      sections from 52 entheses were examined; these entheses encompassed small and
      large insertions in the upper limb (n = 21), lower limb (n = 27), and spine (n =
      4) from 60 cadavers. Enthesis microdamage (fissuring) as well as vascular and
      reparative changes were evaluated. Contact radiographs were used to ascertain the
      relationship between entheses and the trabecular network. RESULTS: At virtually
      all fibrocartilaginous entheses, the deep cortical boundary was extremely thin
      (typically 50-600 microm) or indistinguishable, and 96% of entheses had small
      holes in the cortical shell (typically 100-400 microm wide). Such regions were
      frequent sites of bone formation and renewal (96%) and microdamage (31%); these
      changes were more common in the lower limb. The presence of blood vessels near
      holes in the cortical shell was common; in 85% of attachments, blood vessels were
      present on the soft tissue side of the enthesis. Highly orientated trabeculae
      were more obvious in the lower limb than the upper limb (59% versus 29%).
      CONCLUSION: The trabecular network supporting the cortical shell is an integral
      part of the enthesis, transferring load to an extensive skeletal region. In many
      cases, tendons/ligaments are anchored directly to such networks. This functional
      integration is associated with microdamage and repair at the hard tissue-soft
      tissue interface. These findings have implications for understanding bone
      involvement in SpA and for the SpA concept in general, especially the hypothesis
      that enthesis-bone architecture may be important in disease initiation.

PMID- 17195227
TI  - Association of a TNAP haplotype with ankylosing spondylitis.
AB  - OBJECTIVE: To use a candidate gene approach to the identification of genetic
      markers that are significantly associated with ankylosing spondylitis (AS).
      METHODS: We genotyped 201 multiplex AS families with 1 exonic and 5 intronic
      single-nucleotide polymorphisms (SNPs) in TNAP, the gene that encodes tissue
      nonspecific alkaline phosphatase, and performed family-based association
      analyses. RESULTS: In our cohort of 201 multiplex AS families, the TNAP haplotype
      rs3767155 (G)/rs3738099 (G)/rs1780329 (T) was significantly associated with AS (P
      = 0.032 by additive model). Haplotype-Based Association Testing (HBAT) analyses
      of AS families in which both men and women were affected showed that the same
      TNAP haplotype was significantly associated with AS (P = 0.002 by additive
      model). Using setafftrait code 1 0 0 in the HBAT program, testing specifically
      for affected men in AS families containing affected individuals of both sexes,
      this TNAP haplotype was also significantly associated with AS (P = 0.001 by
      additive model). The HBAT -p option (haplotype permutation test) was used to
      compute the "exact" P value via a Monte Carlo method for each haplotype
      (haplotype permutation test) and for the minimum observed P value among the
      haplotypes (whole marker permutation using the minimal P test), and both P values
      were statistically significant (2-sided P value for haplotype rs3767155
      [G]/rs3738099 [G]/rs1780329 [T] = 0.00059, the smallest observed P value among
      all the individual haplotype scores = 0.003). Interestingly, this haplotype was
      not associated with AS in affected women from the same families. CONCLUSION: Our
      results indicate that the TNAP haplotype rs3767155 (G)/rs3738099 (G)/rs1780329
      (T) is a novel genetic marker in men that is significantly associated with AS in
      multiplex families containing affected individuals of both sexes.

PMID- 17195229
TI  - A serology-based approach combined with clinical examination of 125 Ro/SSA
      positive patients to define incidence and prevalence of subacute cutaneous lupus
      erythematosus.
AB  - OBJECTIVE: To estimate the incidence and prevalence of Ro/SSA-positive subacute
      cutaneous lupus erythematosus (SCLE) in Stockholm County, Sweden (1.8 million
      inhabitants) and to investigate the frequency of photosensitivity and other
      clinical manifestations associated with Ro/SSA autoantibodies. METHODS: Ro/SSA
      positive patients in Stockholm were identified via registry-based searches. All
      patients who tested positive for the presence of Ro/SSA autoantibodies during
      1996-2002 (n = 1,323; 85% women) were identified. A questionnaire was sent to all
      patients still living in Stockholm in 2003 (n = 1,048). Patients who reported
      having skin symptoms and photosensitivity (n = 125) underwent a clinical
      examination. RESULTS: Of the 741 (71%) of 1,048 Ro/SSA-positive patients who
      responded to the questionnaire, 400 (54%) reported having photosensitivity, and
      of these patients, 125 agreed to be clinically examined. A diagnosis of LE was
      confirmed in 59 of the 125 patients (SCLE in 20, systemic LE [SLE] in 33, and
      chronic CLE in 6). Eighty-six patients reported experiencing symptoms consistent
      with polymorphous light eruption (PLE). Comorbidities such as cardiovascular
      disease, autoimmune disease, and other skin diseases were common. The incidence
      of Ro/SSA-positive SCLE during the study period was estimated to be 0.7 cases per
      100,000 persons per year and the prevalence was approximately 6.2-14 in 100,000
      persons. CONCLUSION: The incidence of Ro/SSA-positive SCLE in Stockholm County,
      Sweden is estimated to be 0.7 per 100,000 persons per year as compared with an
      incidence of SLE in Sweden of 4.8 per 100,000 persons per year. The prevalence is
      estimated to be 6.2-14 in 100,000 persons. Self-reported photosensitivity
      commonly corresponds to a history of PLE in Ro/SSA-positive patients, even when
      the clinical profile of SCLE is absent. Photoprotection should therefore be
      included in the treatment recommendations for these patients.

PMID- 17195228
TI  - Effect of glutathione S-transferase polymorphisms and proximity to hazardous
      waste sites on time to systemic lupus erythematosus diagnosis: results from the
      Roxbury lupus project.
AB  - OBJECTIVE: The high prevalence of systemic lupus erythematosus (SLE) among
      African American women may be due to environmental exposures, genetic factors, or
      a combination of factors. Our goal was to assess association of residential
      proximity to hazardous waste sites and genetic variation in 3 glutathione
      Stransferase (GST) genes (GSTM1, GSTT1, and GSTP1) with age at diagnosis of SLE.
      METHODS: Residential histories were obtained by interviewing 93 SLE patients from
      3 predominantly African American neighborhoods in Boston. Residential addresses
      and locations of 416 hazardous waste sites in the study area were geocoded using
      ArcView software. Time-varying Cox models were used to study the effect of
      residential proximity to hazardous sites, GST genotype, and interaction between
      genotype and exposure in determining age at diagnosis. RESULTS: The prevalence of
      SLE among African American women in these neighborhoods was 3.56 SLE cases per
      1,000. Homozygosity for GSTM1-null and GSTP1 Ile105Val in combination was
      associated with earlier SLE diagnosis (P = 0.03), but there was no association
      with proximity to 416 hazardous sites. Available data on specific site
      contaminants suggested that, at a subset of 67 sites, there was higher potential
      risk for exposure to volatile organic compounds (P < 0.05 with Bonferroni
      correction). GST genotypes had a significant interaction with proximity (P =
      0.03) in analyses limited to these sites. CONCLUSION: There was no independent
      association between residential proximity to hazardous waste sites and the risk
      of earlier SLE diagnosis in this urban population. However, analysis of a limited
      number of sites indicated that the risk of earlier SLE associated with proximity
      to hazardous sites might be modulated by GST polymorphisms.

PMID- 17195230
TI  - Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus:
      an international inception cohort study.
AB  - OBJECTIVE: To describe the prevalence, characteristics, attribution, and clinical
      significance of neuropsychiatric (NP) events in an international inception cohort
      of systemic lupus erythematosus (SLE) patients. METHODS: The study was conducted
      by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were
      enrolled within 15 months of fulfilling the American College of Rheumatology
      (ACR) SLE classification criteria. All NP events within a predefined enrollment
      window were identified using the ACR case definitions of 19 NP syndromes.
      Decision rules were derived to determine the proportion of NP disease
      attributable to SLE. Clinical significance was determined using the Short Form 36
      (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). RESULTS: A total of
      572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14
      years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the
      enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total,
      there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion
      of NP events attributed to SLE varied from 19% to 38% using alternate attribution
      models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of
      attribution, had lower scores on the SF-36 and higher SDI scores compared with
      patients with no NP events. CONCLUSION: Twenty-eight percent of SLE patients
      experienced at least 1 NP event around the time of diagnosis of SLE, of which
      only a minority were attributed to SLE. Regardless of attribution, the occurrence
      of NP events was associated with reduced quality of life and increased organ
      damage.

PMID- 17195231
TI  - Effects of short-term infliximab therapy on autoantibodies in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To analyze changes in autoantibodies occurring in patients with
      systemic lupus erythematosus (SLE) treated with 4 infusions of the chimeric anti
      tumor necrosis factor alpha (TNFalpha) antibody infliximab. METHODS: In an open
      label safety study, 7 patients with SLE were treated with infliximab at weeks 0,
      2, 6, and 10 in combination with azathioprine or methotrexate. Antibodies to
      double-stranded DNA (dsDNA) were determined by radioimmunoassay and the Crithidia
      luciliae indirect immunofluorescence assay; anticardiolipin antibodies (aCL) and
      antibodies to histone and chromatin were measured by enzyme-linked immunosorbent
      assay. Antihistone antibodies were also analyzed by immunoblotting. Peripheral
      blood mononuclear cells from healthy individuals and SLE patients were incubated
      for 2 weeks with or without TNFalpha. TNFalpha was removed by washing and by the
      addition of infliximab. Apoptotic cells were stained with annexin V and analyzed
      by flow cytometry. RESULTS: Autoantibodies to dsDNA increased in 5 of 7 patients.
      Histone, chromatin, and IgM aCL levels were increased in 4 of 7, 6 of 7, and 4 of
      7 patients, respectively, peaking 4-10 weeks after the last infliximab infusion,
      but falling to baseline levels or lower thereafter. In the in vitro experiments,
      TNF withdrawal after long-term incubation with recombinant human TNF led to
      increased percentages of apoptotic cells. CONCLUSION: While TNF blockade was
      clinically effective, the majority of SLE patients treated with infliximab showed
      an increase in autoantibodies to nuclear antigens and phospholipids. These
      increases were transient and were not associated with disease flares. Increased
      availability of apoptotic antigens after TNF blockade may play a role in the
      autoantibody formation induced by TNF blockade.

PMID- 17195233
TI  - Altered lipid raft-associated proximal signaling and translocation of CD45
      tyrosine phosphatase in B lymphocytes from patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: B lymphocytes from patients with systemic lupus erythematosus (SLE)
      exhibit defective intracellular signaling, hyperactivity, and autoantibody
      production. Recent evidence indicates a reduced expression of Lyn kinase, a
      negative regulator of B cell signaling, and reduced translocation of Lyn into
      membrane signaling domains in SLE. The present study was undertaken to
      investigate the causes of this altered regulation of Lyn by assessing the
      expression levels of regulatory molecules and their translocation into the
      signaling domains of SLE B lymphocytes. METHODS: Blood was obtained from 48
      patients with SLE and 28 healthy controls for the assessment of B lymphocytes.
      Levels and intracellular distribution of Lyn, CD45, COOH-terminal Src kinase
      (Csk), and c-Cbl were studied by Western blotting, confocal microscopy, and flow
      cytometry. The kinetics of signaling molecule translocation to the B cell
      receptor (BCR)-antigen synapse were investigated by confocal microscopy. RESULTS:
      A profound alteration in the expression and translocation of regulatory signaling
      molecules in membrane domains of B cells from patients with SLE was observed. B
      lymphocytes from SLE patients, but not those from healthy controls, expressed a
      low molecular weight isoform of CD45 in lipid raft signaling microdomains.
      Kinetic studies revealed that translocation of Lyn, CD45, Csk, and c-Cbl led to
      increased recruitment and retention of Lyn and CD45 in the BCR-antigen synapse in
      SLE B cells. CONCLUSION: The results provide evidence of altered expression and
      translocation/interaction of kinases and phosphatases in membrane signaling
      microdomains of B cells from patients with SLE. Altered translocation of CD45
      correlated with reduced expression of Lyn, indicating that Lyn is a key molecule
      in the regulation of BCR-mediated signaling.

PMID- 17195232
TI  - Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of
      human beta(2)-glycoprotein I: mutation studies including residues R39 to R43.
AB  - OBJECTIVE: Pathogenic antiphospholipid antibodies (aPL) bind the self antigen N
      terminal domain (domain I) of beta(2)-glycoprotein I (beta(2)GPI), with residues
      G40-R43 being important. However, peptides homologous to other regions of domain
      I have also been shown to bind aPL. Furthermore, there are no published reports
      of the effects of altering R39, which has greater surface exposure than the G40
      R43 residues. METHODS: We used a novel, efficient method of production and
      purification of human domain I by Escherichia coli to create multiple mutants of
      domain I. These domain I mutants were then screened for binding to a range of
      polyclonal IgG purified from patients with antiphospholipid syndrome, using both
      solid-phase and fluid-phase assays. RESULTS: E coli-expressed purified domain I
      selectively bound IgG derived from patients with antiphospholipid syndrome. In
      region R39-R43, the R39S mutation had the greatest effect in terms of reducing
      binding to a panel of aPL in the fluid phase (mean +/- SD inhibition 14 +/- 18.5%
      versus 44.1 +/- 31.7% for G40E and 62.9 +/- 25.7% for wild-type domain I).
      Conversely, altering both D8 and D9 to S8 and G9, respectively, had the effect of
      enhancing binding to aPL in the fluid phase. Adding the remainder of the domain I
      II interlinker resulted in enhanced binding over wild-type in the solid phase but
      not the fluid phase. CONCLUSION: The binding of aPL to beta(2)GPI domain I is
      complex and likely to involve discontinuous epitopes that include R39 in addition
      to G40-R43, the domain I-II interlinker, and possibly D8 and D9. Domain I
      variants with enhanced binding to aPL compared with wild-type domain I may aid in
      the development of novel therapies.

PMID- 17195234
TI  - Natural killer T cells in families of patients with systemic lupus erythematosus:
      their possible role in regulation of IGG production.
AB  - OBJECTIVE: To determine whether there is a link between the frequency of natural
      killer T (NKT) cells and high levels of IgG in patients with systemic lupus
      erythematosus (SLE) and their relatives. METHODS: Blood samples were obtained
      from patients with SLE, their first-degree relatives, patients with rheumatoid
      arthritis (RA), and healthy control subjects. The frequency of NKT cells (defined
      as CD56+ T cells) was expressed as a percentage of total blood lymphocytes.
      Plasma levels of total IgG and IgM, and IgG antibodies to double-stranded DNA
      (dsDNA) were determined. RESULTS: The frequency of NKT cells was lower in
      patients with SLE than in control subjects. No such decrease was observed in the
      relatives of patients with SLE or in patients with RA. High levels of IgG were
      observed in both patients with SLE and their relatives, while low levels of IgM
      were observed in these same groups. In relatives of patients with SLE, an inverse
      correlation between the frequency of NKT cells and IgG levels was observed.
      Moreover, raised levels of IgG in patients with SLE and their relatives and high
      levels of IgG anti-dsDNA in patients were associated with low frequencies of NKT
      cells. CONCLUSION: These results suggest that NKT cells have an important role in
      the regulation of IgG production, although NKT cells with invariant T cell
      receptors may not necessarily be involved. NKT cells in the setting of SLE could
      lack the cytokine stimulus from NK or other cells that is needed to exert control
      on IgG production. Enhancement of NKT cell activity may provide a novel basis for
      therapy in SLE.

PMID- 17195235
TI  - Imatinib mesylate reduces production of extracellular matrix and prevents
      development of experimental dermal fibrosis.
AB  - OBJECTIVE: Imatinib mesylate is a clinically well-tolerated small molecule
      inhibitor that exerts selective, dual inhibition of the transforming growth
      factor beta (TGFbeta) and platelet-derived growth factor (PDGF) pathways. This
      study was undertaken to test the potential use of imatinib mesylate as an
      antifibrotic drug for the treatment of dermal fibrosis in systemic sclerosis
      (SSc). METHODS: The expression of extracellular matrix (ECM) proteins in SSc and
      normal dermal fibroblasts was analyzed by real-time polymerase chain reaction,
      Western blot, and Sircol collagen assay. Proliferation capacity was assessed with
      the MTT assay. Cell viability was analyzed by mitochondrial membrane potential
      and by annexin V/propidium iodide staining. Bleomycin-induced experimental dermal
      fibrosis was used to assess the antifibrotic effects of imatinib mesylate in
      vivo. RESULTS: Imatinib mesylate efficiently reduced basal synthesis of COL1A1,
      COL1A2, and fibronectin 1 messenger RNA in SSc and normal dermal fibroblasts, in
      a dose-dependent manner. The induction of ECM proteins after stimulation with
      TGFbeta and PDGF was also strongly and dose-dependently inhibited by imatinib
      mesylate. These results were confirmed at the protein level. Imatinib mesylate
      did not alter proliferation or induce apoptosis and necrosis in dermal
      fibroblasts. Consistent with the in vitro findings, imatinib mesylate reduced
      dermal thickness, the number of myofibroblasts, and synthesis of ECM proteins in
      experimental dermal fibrosis, without evidence of toxic side effects. CONCLUSION:
      These data show that imatinib mesylate at biologically relevant concentrations
      has potent antifibrotic effects in vitro and in vivo, without toxic side effects.
      Considering its favorable pharmacokinetics and clinical experience with its use
      in other diseases, imatinib mesylate is a promising candidate for the treatment
      of fibrotic diseases such as SSc.

PMID- 17195236
TI  - Recombinant human anti-transforming growth factor beta1 antibody therapy in
      systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II
      trial of CAT-192.
AB  - OBJECTIVE: To evaluate CAT-192, a recombinant human antibody that neutralizes
      transforming growth factor beta1 (TGFbeta1), in the treatment of early-stage
      diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Patients with SSc duration
      of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192
      treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and
      weeks 6, 12, and 18. The primary objective of this study was to evaluate the
      safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes
      included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health
      Assessment Questionnaire, assessment of organ-based disease, serum levels of
      soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I
      [PINP] and type III collagen), and tissue levels of messenger RNA for
      procollagens I and III and for TGFbeta1 and TGFbeta2. RESULTS: Forty-five
      patients were enrolled. There was significant morbidity and mortality, including
      1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group
      receiving 5 mg/kg of CAT-192. There were more adverse events and more serious
      adverse events in patients receiving CAT-192 than in those receiving placebo,
      although these events were not more frequent in the high-dose treatment group.
      The MRSS improved in all groups during the study, but there was no evidence of a
      treatment effect for CAT-192. Improvement in the MRSS correlated with the disease
      duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline
      correlated with changes in the MRSS (r = 0.37, P = 0.027). CONCLUSION: We report
      the first evaluation of a systemically administered and repeatedly dosed anti
      TGFbeta1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no
      evidence of efficacy. The utility of clinical and biochemical outcome measures
      and the feasibility of multicenter trials of early dcSSc were confirmed.

PMID- 17195237
TI  - Postnatal induction of transforming growth factor beta signaling in fibroblasts
      of mice recapitulates clinical, histologic, and biochemical features of
      scleroderma.
AB  - OBJECTIVE: Increased signaling by transforming growth factor beta (TGFbeta) has
      been implicated in systemic sclerosis (SSc; scleroderma), a complex disorder of
      connective tissues characterized by excessive accumulation of collagen and other
      extracellular matrix components in systemic organs. To directly assess the effect
      of sustained TGFbeta signaling in SSc, we established a novel mouse model in
      which the TGFbeta signaling pathway is activated in fibroblasts postnatally.
      METHODS: The mice we used (termed TBR1(CA); Cre-ER mice) harbor both the DNA for
      an inducible constitutively active TGFbeta receptor I (TGFbetaRI) mutation, which
      has been targeted to the ROSA locus, and a Cre-ER transgene that is driven by a
      fibroblast-specific promoter. Administration of 4-hydroxytamoxifen 2 weeks after
      birth activates the expression of constitutively active TGFbetaRI. RESULTS: These
      mice recapitulated clinical, histologic, and biochemical features of human SSc,
      showing pronounced and generalized fibrosis of the dermis, thinner epidermis,
      loss of hair follicles, and fibrotic thickening of small blood vessel walls in
      the lung and kidney. Primary skin fibroblasts from these mice showed elevated
      expression of downstream TGFbeta targets, reproducing the hallmark biochemical
      phenotype of explanted SSc dermal fibroblasts. The mouse fibroblasts also showed
      elevated basal expression of the TGFbeta-regulated promoters plasminogen
      activator inhibitor 1 and 3TP, increased Smad2/3 phosphorylation, and enhanced
      myofibroblast differentiation. CONCLUSION: Constitutive activation of TGFbeta
      signaling in fibroblastic cells of mice after birth caused a marked fibrotic
      phenotype characteristic of SSc. These mice should be excellent models with which
      to test therapies aimed at correcting excessive TGFbeta signaling in human
      scleroderma.

PMID- 17195238
TI  - Association between reduced levels of MEFV messenger RNA in peripheral blood
      leukocytes and acute inflammation.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is associated with more than 70
      missense mutations in the MEFV gene. The purpose of this study was to investigate
      the relative expression of messenger RNA (mRNA) for the MEFV gene in peripheral
      blood leukocytes (PBLs) obtained from patients with FMF during attacks of acute
      abdominal inflammation as well as during asymptomatic periods. METHODS: We
      studied 16 patients with FMF during an attack of acute peritonitis and 17
      otherwise healthy individuals who were undergoing surgery because of acute
      appendicitis. Blood samples were collected from both groups of patients during
      both acute inflammatory and asymptomatic periods. Relative levels of MEFV mRNA in
      PBLs were detected with real-time reverse transcriptase-polymerase chain reaction
      using LightCycler, with 2 sets of primers for the MEFV gene (exons 7-10 and exons
      2-3) and with primers for CIAS1 and PSTPIP1 genes. Expression levels were
      compared with beta(2)-microglobulin as an internal control. RESULTS: MEFV
      expression was reduced in FMF patients during asymptomatic periods as compared
      with the non-FMF controls (P < 0.001). We observed a further decrease in MEFV
      expression in FMF patients during periods of inflammation (P = 0.01). Reduced
      levels of MEFV mRNA were also noted during the preoperative period as compared
      with asymptomatic periods in control patients with acute appendicitis (P = 0.01).
      CIAS1 expression in PBLs from patients with FMF was also found to be lower than
      that in the control patients. However, CIAS1 expression did not change with acute
      inflammation. CONCLUSION: This study confirmed that reduced expression of the
      MEFV gene is associated with inflammation and that it may be one of the
      pathogenic mechanisms of the attacks of inflammation in FMF patients, along with
      disease-associated variations in pyrin.

PMID- 17195239
TI  - Sensitization of unmyelinated sensory fibers of the joint nerve to mechanical
      stimuli by interleukin-6 in the rat: an inflammatory mechanism of joint pain.
AB  - OBJECTIVE: Pain during mechanical stimulation of the joint and spontaneous pain
      are major symptoms of arthritis. An important neuronal process of mechanical
      hypersensitivity of the joint is the sensitization of thin myelinated Adelta
      fibers and unmyelinated C fibers innervating the joint. Because interleukin-6 (IL
      6) is a major inflammatory mediator, we investigated whether this cytokine has
      the potential to sensitize joint afferents to mechanical stimuli. METHODS: In
      electrophysiologic experiments conducted on anesthetized rats, action potentials
      were recorded from afferent fibers supplying the knee joint. Responses to
      innocuous and noxious rotation of the tibia against the femur in the knee joint
      were monitored before and 1-2 hours after injection of test compounds into the
      joint cavity. RESULTS: Injection of IL-6 and coinjection of IL-6 plus soluble IL
      6 receptor (sIL-6R) caused a gradual increase in the responses of C fibers to
      innocuous and noxious rotation within 1 hour. The increase in responses to IL-6
      and IL-6 plus sIL-6R was prevented by coadministration of soluble glycoprotein
      130 (sgp130), but sgp130 did not reverse established mechanical
      hyperexcitability. Responses of Adelta fibers were not altered by the compounds.
      While injection of sIL-6R alone into the normal knee joint did not influence
      responses to mechanical stimulation, injection of sIL-6R into the acutely
      inflamed knee joint caused an increase in responses. CONCLUSION: IL-6 has the
      potential to sensitize C fibers in the joint to mechanical stimulation. Thus, IL
      6 contributes to mechanical hypersensitivity, most likely due to an action of IL
      6 on nerve fibers themselves.

PMID- 17195240
TI  - Moderation of psychosocial risk factors through dysfunction of the hypothalamic
      pituitary-adrenal stress axis in the onset of chronic widespread musculoskeletal
      pain: findings of a population-based prospective cohort study.
AB  - OBJECTIVE: To test the hypothesis that abnormalities in the hypothalamic
      pituitary-adrenal (HPA) stress-response system would act as an effect moderator
      between HPA function and the onset of chronic widespread pain (CWP). METHODS: We
      conducted a population-based prospective cohort study. Current pain and
      psychosocial status were ascertained in 11,000 subjects. Of the 768 eligible
      subjects free of CWP but at future risk based on their psychosocial profile, 463
      were randomly selected, and 267 (57.7%) consented to assessment of their HPA axis
      function. Diurnal function was measured by assessing levels of salivary cortisol
      in the morning (9:00 AM) and evening (10:00 PM). Serum cortisol levels were
      measured after an overnight low-dose (0.25 mg) dexamethasone suppression test and
      a potentially stressful clinical examination. All subjects were followed up 15
      months later to identify cases of new-onset CWP. RESULTS: A total of 241 subjects
      (94.9%) completed the followup study, and 28 (11.6%) reported the new onset of
      CWP. High levels of cortisol post-dexamethasone (odds ratio [OR] 3.53, 95%
      confidence interval [95% CI] 1.17-10.65), low levels in morning saliva (OR 1.43,
      95% CI 0.52-3.94), and high levels in evening saliva (OR 2.32, 95% CI 0.64-8.42)
      were all associated with CWP. These 3 factors were found to be independent and
      additive predictors of CWP (OR for all 3 factors 8.5, 95% CI 1.5-47.9) in
      analyses controlling for age, sex, depression, sleep disturbance, recent
      traumatic life events, and pain status. One or more of these 3 HPA factors
      identified 26 (92.9%) cases of new-onset CWP. CONCLUSION: Among a group of
      psychologically at-risk subjects, dysfunction of the HPA axis helps to
      distinguish those who will and will not develop new-onset CWP.

PMID- 17195241
TI  - Restricted T cell receptor BV gene usage in the lungs and muscles of patients
      with idiopathic inflammatory myopathies.
AB  - OBJECTIVE: To investigate T cell receptor (TCR) expression in 3 different
      compartments that could be involved in patients with myositis: muscle, lung, and
      peripheral blood. METHODS: Nine patients with polymyositis (PM), dermatomyositis,
      or inclusion body myositis underwent bronchoscopy and bronchoalveolar lavage
      (BAL) as well as muscle biopsy and blood sampling. A panel of 19 monoclonal
      antibodies specific for TCR V(beta) (BV) and V(alpha) (AV) were used to
      characterize the TCR profile in CD4(+) and CD8(+) T cell populations in BAL fluid
      and peripheral blood by flow cytometry. Muscle biopsy tissues were analyzed by
      immunohistochemistry. Patients were also typed for HLA-DRB1 and DRB3 alleles.
      RESULTS: A total of 17 T cell expansions were detected in BAL fluid, 6 in the
      CD4(+) T cell population and 11 in the CD8(+) T cell population. Four T cell
      expansions were detected in peripheral blood. A selective TCR V usage was found
      in muscle. Two PM patients, both of whom had BAL fluid BV3(+) T cell expansions
      in the CD4 population and in whom BV3 was also a prominent TCR V segment in
      muscle tissue, shared the HLA-DRB1*03 allele. These 2 patients were the only ones
      who were positive for anti-Jo-1 antibody. CONCLUSION: We found a restricted
      accumulation of T lymphocytes expressing selected TCR V-gene segments in the
      target organ compartments (i.e., lung and muscle). The occurrence of shared TCR
      gene segment usage in muscle and lungs could suggest common target antigens in
      these organs.

PMID- 17195242
TI  - Effect of dosage on coxib- or nonsteroidal antiinflammatory drug-associated
      cardiovascular risk? Comment on the article by Solomon et al.

PMID- 17195244
TI  - Methodologic issues in the assessment of the efficacy of radiation synovectomy
      for arthritis of the knee: comment on the article by Janangier et al.

PMID- 17195245
TI  - Evidence of the efficacy of radiation synovectomy with yttrium-90: comment on the
      article by Jahangier et al.

PMID- 17195246
TI  - Specificity of enzyme-linked immunosorbent assay for IgG anti-NR2 glutamate
      receptor antibodies: comment on the concise communication by Yoshio et al.

PMID- 17195247
TI  - Cortisol metabolism by 11 beta-hydroxysteroid dehydrogenase as a novel target in
      the treatment of inflammation- or immune-mediated bone loss: comment on the
      article by Makrygiannakis et al.

PMID- 17195249
TI  - Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea
      flavonoids and teas.
AB  - Tea leaves produce organic compounds that may be involved in the defense of the
      plants against invading pathogens including insects, bacteria, fungi, and
      viruses. These metabolites include polyphenolic compounds, the six so-called
      catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and
      theophylline. Postharvest inactivation of phenol oxidases in green tea leaves
      prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed
      oxidation (fermentation) of catechins in tea leaves results in the formation of
      four theaflavins as well as polymeric thearubigins. These substances impart the
      black color to black teas. Black and partly fermented oolong teas contain both
      classes of phenolic compounds. A need exists to develop a better understanding of
      the roles of polyphenolic tea compounds in food and medical microbiology. This
      overview surveys and interprets our present knowledge of activities of tea
      flavonoids and teas against foodborne and other pathogenic bacteria, virulent
      protein toxins produced by some of the bacteria, virulent bacteriophages,
      pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and
      bioavailability aspects of the antimicrobial effects. Further research is
      suggested for each of these categories. The herein described findings are not
      only of fundamental interest, but also have practical implications for nutrition,
      food safety, and animal and human health.

PMID- 17195250
TI  - Amyloid-beta peptide forms monomeric complexes with Cu(II) and Zn(II) prior to
      aggregation.

PMID- 17195251
TI  - Reversible inactivation of the CG specific SssI DNA (cytosine-C5)
      methyltransferase with a photocleavable protecting group.
AB  - Caging of proteins by conjugation with a photocleavable group is a powerful
      approach for reversibly blocking enzymatic activity. Here we describe the
      covalent modification of the bacterial SssI DNA methyltransferase (M.SssI) with
      the cysteine-specific reagent 4,5-dimethoxy-2-nitrobenzylbromide (DMNBB). M.SssI
      contains two cysteine residues; replacement of the active-site Cys141 with Ser
      resulted in an approximately 100-fold loss of enzymatic activity; this indicates
      an important role for this residue in catalysis. However, replacement of Cys368
      with Ala did not affect methyltransferase activity. Treatment of the Cys368Ala
      mutant enzyme with DMNBB led to an almost complete loss of activity. Irradiation
      of the inactivated enzyme with near-ultraviolet light (320-400 nm) restored 60 %
      of the catalytic activity. This indicates that caging by DMNBB can be used for
      the reversible inactivation of M.SssI.

PMID- 17195252
TI  - Site-specific functionalization of proteins by organopalladium reactions.
AB  - A new carbon-carbon bond has been regioselectively introduced into a target
      position (position 32 or 174) of the Ras protein by two types of organopalladium
      reactions (Mizoroki-Heck and Sonogashira reactions). Reaction conditions were
      screened by using a model peptide, and the stability of the Ras protein under the
      reaction conditions was examined by using the wild-type Ras protein. Finally, the
      iF-Ras proteins containing a 4-iodo-L-phenylalanine residue were subjected to
      organopalladium reactions with vinylated or propargylated biotin. Site-specific
      biotinylations of the Ras protein were confirmed by Western blot and LC-MS/MS.

PMID- 17195253
TI  - Rapid enzymatic isomerization of 12-oxophytodienoic acid in the gut of
      lepidopteran larvae.
AB  - In response to feeding larvae of the Mediterranean climbing cutworm (Spodoptera
      littoralis), leaves of the lima bean (Phaseolus lunatus) produce fatty acid
      derived signaling compounds (oxylipins). The major products are the phytohormones
      jasmonic acid and its biosynthetic precursor 12-oxophytodienoic acid (OPDA),
      along with 13-hydroxy-12-oxooctadeca-9,15-dienoic acid, 9-hydroxy-12-oxooctadeca
      10,15-dienoic acid (alpha- and gamma-ketol), as well as unsaturated aldehydes.
      Oxylipin production is highest at the feeding zone of the insect and decreases
      with distance from the damaged area. Accordingly, the feeding insect experiences
      high local concentrations of oxylipins, which are taken up into the alimentary
      canal and are finally excreted with the feces. In contrast to most other
      oxylipins, OPDA was not detectable in the insect's gut; instead the structurally
      related tetrahydrodicranenone B (iso-OPDA) was identified. Feeding experiments
      with deuterium-labeled OPDA proved that the isomerization is catalyzed by an
      enzyme from the insect's gut tissue. The phenomenon appears to be widespread
      among Lepidopteran larvae.

PMID- 17195256
TI  - Detection of L-DNA-tagged PCR products by surface plasmon resonance imaging.

PMID- 17195257
TI  - High activity of amine-doped H-ZSM-5 zeolite in ethene protonation: revealed by
      embedding calculations.

PMID- 17195254
TI  - High-throughput substrate specificity studies of sialidases by using
      chemoenzymatically synthesized sialoside libraries.
AB  - Sialidases, or neuraminidases, are enzymes that cleave terminal sialic acid (Sia)
      residues from complex sialic acid-containing structures. They have been found in
      many animals and microorganisms and are important in various physiological and
      pathological processes. In order to understand the biological significance of
      diverse sialidases, it is important to study in detail the structural
      determinants of their natural substrates. Here, we report the synthesis of
      sialoside libraries containing para-nitrophenol-tagged sialosides with different
      naturally occurring sialic acid forms, different sialyl linkages, and different
      penultimate monosaccharides using a highly efficient one-pot three-enzyme
      chemoenzymatic approach. By using these compounds in a 96-well plate-based
      colorimetric high-throughput screening platform, the diversity of substrate
      preference is shown for seven bacterial sialidases. The sialoside libraries and
      the screening method are convenient tools for unravelling the substrate
      specificity and the biological function of sialidases.

PMID- 17195255
TI  - A comparative analysis of the sugar phosphate cyclase superfamily involved in
      primary and secondary metabolism.
AB  - Sugar phosphate cyclases (SPCs) catalyze the cyclization of sugar phosphates to
      produce a variety of cyclitol intermediates that serve as the building blocks of
      many primary metabolites, for example, aromatic amino acids, and clinically
      relevant secondary metabolites, for example, aminocyclitol/aminoglycoside and
      ansamycin antibiotics. Feeding experiments with isotopically labeled cyclitols
      revealed that cetoniacytone A, a unique C(7)N-aminocyclitol antibiotic isolated
      from an insect endophytic Actinomyces sp., is derived from 2-epi-5-epi-valiolone,
      a product of SPC. By using heterologous probes from the 2-epi-5-epi-valiolone
      synthase class of SPCs, an SPC homologue gene, cetA, was isolated from the
      cetoniacytone producer. cetA is closely related to BE-orf9 found in the BE-40644
      biosynthetic gene cluster from Actinoplanes sp. strain A40644. Recombinant
      expression of cetA and BE-orf9 and biochemical characterization of the gene
      products confirmed their function as 2-epi-5-epi-valiolone synthases. Further
      phylogenetic analysis of SPC sequences revealed a new clade of SPCs that might
      regulate the biosynthesis of a novel set of secondary metabolites.

PMID- 17195258
TI  - Application of CE for determination of DNA base composition.
AB  - DNA base composition expressed as mol% of guanine plus cytosine (% GC) or GC
      content is a key parameter of bacterial taxonomy and genomic analyses. Direct
      chemical determination methods such as HPLC as well as indirect methods based on
      physical properties of deoxyribonucleic acid (DNA), melting point (T(m)), and
      buoyant density (B(d)) have been conventionally applied to determine the GC
      content. However, these methods require relatively large amounts of sample DNA,
      time, and labor. We have developed a protocol to determine the GC content by fine
      separation of nucleosides with CZE. Genomic DNAs with known GC content from 23
      bacterial strains were determined by CE at the optimized conditions of 27 degrees
      C, 20 kV in 50 mM of NaHCO(3) (pH 9.0) and 70 mM SDS added. Nucleosides from <1
      microg of DNA hydrolyzed with nuclease-P1 and bacterial alkaline phosphatase were
      separated in a 75 microm wide and 80 cm long silica capillary. The nucleoside
      peak areas were determined at 254 nm in less than 12 min. The CE-based
      determination of GC content requires only small amounts of DNA, and thus should
      be applicable to environmental genomics (metagenomics), as >90% of environmental
      micro-organisms are nonculturable and produce only small amounts of genomic DNA.

PMID- 17195259
TI  - Analysis of serine proteases from marine sponges by 2-D zymography.
AB  - Proteolytic activities isolated from the marine demosponges Geodia cydonium and
      Suberites domuncula were analyzed by 2-D zymography, a technique that combines
      IEF and zymography. After purification, a 200 kDa proteolytically active protein
      band was obtained from G. cydonium when analyzed in gelatin copolymerized 1-D
      zymograms. The enzymatic activity was quantified using alpha-N-benzoyl-D-arginine
      p-nitroanilide (BAPNA) as a substrate and corresponded to a serine protease. The
      protease activity was resistant to urea and SDS. DTT and 2-mercaptoethanol (2-ME)
      did not significantly change the protease activity, but induced a shift in
      molecular mass of the proteolytic band to lower M(r) values as detected by
      zymography. Under mild denaturing conditions, lower M(r) bands (<200 kDa) were
      identified in 1-D zymograms, suggesting that the protease is composed of subunits
      which retain the catalytic activity. After 2-D zymography, the protease from G.
      cydonium revealed a pI of 8.0 and an M(r) shift from 200 to 66 kDa. To contrast
      these results, a cytosolic sample from S. domuncula was analyzed. The proteolytic
      activity of this sponge after 2-D zymography corresponded to an M(r) of 40 kDa
      and a pI of 4.0. The biological function of both sponge proteases is not yet
      known. This study demonstrates that mild denaturing conditions required for IEF
      may alter the interpretation of the 2-D zymography, and care must be taken during
      sample preparation.

PMID- 17195260
TI  - Mapping of Malus domestica allergens by 2-D electrophoresis and IgE-reactivity.
AB  - The importance of apple allergens has been repeatedly emphasized, and their
      presence has been confirmed both in pollen and in fruits. In the present study, a
      combination of proteomic tools have been used to build a complete allergen map of
      apple. The water-soluble fraction of an apple extract was precipitated using a
      phenol-based procedure and separated by 2-DE. Initially four previously
      classified allergens, Mal d 1, Mal d 2, Mal d 3 and Mal d 4, could be identified
      in Western blots with polyclonal rabbit antibodies directed to the four
      respective allergens, and subsequently matched to the bands recognized by several
      patient sera. Further, all four known apple allergens were localized on a 2-DE
      map and they were matched with spots recognized by sera of patients with
      different allergic patterns. Moreover, a new, putative allergen could be
      identified using MS. We evaluated the influence of post-translational
      modifications and the immunoreactivity under different analytical conditions. The
      comparison of different visualization methods for 2-DE gels and blots revealed
      that even very low concentrations of the intact epitopes are detectable by IgEs
      of patients, and therefore might be sufficient to trigger allergic symptoms in
      sensitized individuals.

PMID- 17195261
TI  - Development of a CZE method for the determination of mizolastine and its
      impurities in pharmaceutical preparations using response surface methodology.
AB  - A fast and selective CZE method for the determination of mizolastine and related
      impurities is described. Response surface methodology was applied to study the
      influence of phosphate/triethanolamine (TEA) buffer concentration, heptakis(2,3,6
      tri-O-methyl)-beta-CD (TMbetaCD) concentration, voltage and temperature. The
      optimum conditions were: 105 mM phosphate/TEA buffer (pH 3.0) containing 10 mM
      TMbetaCD, temperature 19 degrees C and voltage 30 kV. Validation of the method
      was performed in drug substance and drug product. Robustness was evaluated using
      a Plackett-Burman design, including pH among the considered factors. Applying the
      optimal conditions, the nine peaks were baseline separated in about 10 min. The
      method was applied to the quality control of mizolastine in controlled-release
      tablets.

PMID- 17195262
TI  - Context is everything: Mining the normal and preneoplastic microenvironment for
      insights into the diet and cancer risk conundrum.
AB  - This review highlights the context-dependence of epithelial carcinogenesis in
      order to illuminate the potential for progress in the field of diet and cancer
      prevention. Estimates drawn from observational epidemiology imply that diet and
      lifestyle changes have the potential to prevent 30-40% of cancer cases. However,
      the application of knowledge gleaned from observational epidemiology applied to
      randomized clinical trials (RCT) has yielded equivocal or negative results.
      Resolving this conundrum requires: (i) advances in diet assessment methodologies
      and the design of clinical trials; (ii) greater knowledge of the active
      components within foods which may impact cancer risk; and (iii) knowledge about
      the effects of dietary components on susceptible tissues throughout the disease
      process (Meyskens, F. L., Jr., Szabo, E., Diet and cancer: The disconnect between
      epidemiology and RCT. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 1366-1369).
      Explicit consideration of the causal criteria will pay tangible benefits in the
      design of basic, clinical, and epidemiologic studies in cancer prevention. The
      rational identification of diet-dependent physiologic targets for cancer
      prevention is best pursued by appreciating context-dependence of epithelial
      carcinogenesis. Five contexts, or paradigms useful in understanding the
      multifactorial nature of carcinogenesis, are offered which describe the potential
      diet-associated physiologic influences on normal and preneoplastic cells and
      tumor microenvironments. Taken together with the interactions of systemic,
      endocrine, and autocrine/paracrine signals that may modulate the process of
      carcinogenesis, we can appreciate how dietary factors may act collectively in
      normal tissues or at early stages of carcinogenesis to prevent cancer. Only by
      understanding the effect of dietary components on the cellular and stromal
      components of the tissue microenvironment early in the process of epithelial
      carcinogenesis will yield clues useful for the development of improved strategies
      for cancer prevention.

PMID- 17195264
TI  - Cleavable dendrimers.

PMID- 17195263
TI  - Intestinal absorption of dietary carotenoids.
AB  - The assessment of carotenoid bioavailability has long been hampered by the
      limited knowledge of their absorption mechanisms. However, recent reports have
      elucidated important aspects of carotenoid digestion and absorption. Disruption
      of food matrix and increasing amounts of fat seem to enhance the absorption of
      carotenes to a larger extent than that of xanthophylls. Comparing different
      carotenoid species, xanthophylls seem to be more easily released from the food
      matrix and more efficiently micellized than the carotenes. On the other hand,
      carotenes are more efficiently taken up by the enterocytes. However, carotenoid
      emulsification and micellization steps are largely affected by the food matrix
      and dietary components, being the main determinant of carotenoid bioavailability
      from foodstuffs. Although the intestinal uptake of carotenoids has been thought
      to occur by simple diffusion, recent studies reported the existence of receptor
      mediated transport of carotenoids in enterocytes. Comparisons between the
      intestinal absorption of a wide array of carotenoids would be useful to elucidate
      the absorption mechanism of each carotenoid species, in view of the recent
      indications that intestinal carotenoid uptake may involve the scavenger receptor
      class B type I and possibly other epithelial transporters. The unraveling of the
      whole mechanism underlying the absorption of carotenoids will be the challenge
      for future studies.

PMID- 17195265
TI  - Evidence for a pi dimer in the electrochemical reduction of 1,3,5
      trinitrobenzene: a reversible N2-fixation system.

PMID- 17195266
TI  - Linking chemistry and biology for the study of protein function.

PMID- 17195267
TI  - Site-specific recognition of nanophase-separated surfaces of amphiphilic block
      copolymers by hydrophilic and hydrophobic gold nanoparticles.

PMID- 17195269
TI  - A new approach for an organocatalytic multicomponent domino asymmetric reaction.

PMID- 17195268
TI  - Superstructure formation and rearrangement in the adlayer of a rare-Earth-metal
      triple-decker sandwich complex at the electrochemical interface.

PMID- 17195270
TI  - Alkali-metal-mediated manganation: a method for directly attaching manganese(II)
      centers to aromatic frameworks.

PMID- 17195271
TI  - IgE-mediated food allergy diagnosis: Current status and new perspectives.
AB  - In June 2005, the work of the EU Integrated Project EuroPrevall was started.
      EuroPrevall is the largest research project on food allergy ever performed in
      Europe. Major aims of the project are to generate for the first time reliable
      data on the prevalence of food allergies across Europe and on the natural course
      of food allergy development in infants. Improvement of in vitro diagnosis of food
      allergies is another important aim of the project. The present review summarizes
      current knowledge about the clinical presentation of food allergy and critically
      reviews available diagnostic tools at the beginning of the project period. A
      major problem in diagnosis is a relatively poor 'clinical specificity', i. e.
      both positive skin tests and in vitro tests for specific IgE are frequent in
      sensitized subjects without food allergy symptoms. So far, no in vitro test
      reliably predicts clinical food allergy. EuroPrevall aims at improving the
      predictive value of such tests by proceeding from diagnosis based on allergen
      extracts to purified allergen molecules, taking into account the affinity of the
      IgE-allergen interaction, and evaluating the potential of biological in vitro
      tests such as histamine release tests or basophil activation tests including
      assays performed with permanently growing cell lines.

PMID- 17195272
TI  - Improved quality of life to food allergic consumers.

PMID- 17195275
TI  - Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans.
AB  - Ochratoxin A (OTA) is a ubiquitous mycotoxin produced by fungi of improperly
      stored food products. OTA is nephrotoxic and is suspected of being the main
      etiological agent responsible for human Balkan endemic nephropathy (BEN) and
      associated urinary tract tumours. Striking similarities between OTA-induced
      porcine nephropathy in pigs and BEN in humans are observed. International Agency
      for Research on Cancer (IARC) has classified OTA as a possible human carcinogen
      (group 2B). Currently, the mode of carcinogenic action by OTA is unknown. OTA is
      genotoxic following oxidative metabolism. This activity is thought to play a
      central role in OTA-mediated carcinogenesis and may be divided into direct
      (covalent DNA adduction) and indirect (oxidative DNA damage) mechanisms of
      action. Evidence for a direct mode of genotoxicity has been derived from the
      sensitive 32P-postlabelling assay. OTA facilitates guanine-specific DNA adducts
      in vitro and in rat and pig kidney orally dosed, one adduct comigrates with a
      synthetic carbon (C)-bonded C8-dG OTA adduct standard. In this paper, our current
      understanding of OTA toxicity and carcinogenicity are reviewed. The available
      evidence suggests that OTA is a genotoxic carcinogen by induction of oxidative
      DNA lesions coupled with direct DNA adducts via quinone formation. This mechanism
      of action should be used to establish acceptable intake levels of OTA from human
      food sources.

PMID- 17195276
TI  - Toxins of cyanobacteria.
AB  - Blue-green algae are found in lakes, ponds, rivers and brackish waters throughout
      the world. In case of excessive growth such as bloom formation, these bacteria
      can produce inherent toxins in quantities causing toxicity in mammals, including
      humans. These cyanotoxins include cyclic peptides and alkaloids. Among the cyclic
      peptides are the microcystins and the nodularins. The alkaloids include anatoxin
      a, anatoxin-a(S), cylindrospermopsin, saxitoxins (STXs), aplysiatoxins and
      lyngbyatoxin. Both biological and chemical methods are used to determine
      cyanotoxins. Bioassays and biochemical assays are nonspecific, so they can only
      be used as screening methods. HPLC has some good prospects. For the subsequent
      detection of these toxins different detectors may be used, ranging from simple UV
      spectrometry via fluorescence detection to various types of MS. The main problem
      in the determination of cyanobacterial toxins is the lack of reference materials
      of all relevant toxins. In general, toxicity data on cyanotoxins are rather
      scarce. A majority of toxicity data are known to be of microcystin-LR. For
      nodularins, data from a few animal studies are available. For the alkaloids,
      limited toxicity data exist for anatoxin-a, cylindrospermopsin and STX. Risk
      assessment for acute exposure could be relevant for some types of exposure.
      Nevertheless, no acute reference doses have formally been derived thus far. For
      STX(s), many countries have established tolerance levels in bivalves, but these
      limits were set in view of STX(s) as biotoxins, accumulating in marine shellfish.
      Official regulations for other cyanotoxins have not been established, although
      some (provisional) guideline values have been derived for microcystins in
      drinking water by WHO and several countries.

PMID- 17195277
TI  - Customized PEG-derived copolymers for tissue-engineering applications.
AB  - PEG-containing copolymers play a prominent role as biomaterials for different
      applications ranging from drug delivery to tissue engineering. These custom
      designed materials offer enormous possibilities to change the overall
      characteristics of biomaterials by improving their biocompatibility and
      solubility, as well as their ability to crystallize in polymer blends and to
      resist protein adsorption. This article demonstrates various principles of PEG
      based material design that are applied to fine tune the properties of
      biomaterials for different tissue engineering applications. More specifically,
      strategies are described to develop PEG copolymers with various block
      compositions and specific bulk properties, including low melting points and
      improved surface hydrophilicity. Highly hydrated polymer gel networks for
      promoting cellular growth or suppressing protein adsorption and cell adhesion are
      introduced. By incorporating selectively cleavable cross-links, these hydrophilic
      polymers can also serve as smart hydrogel scaffolds, mimicking the natural
      extracellular matrix for cell cultivation and tissue growth. Ultimately, these
      developments lead to the creation of biomimetic materials to immobilize bioactive
      compounds, allowing precise control of cellular adhesion and tissue growth.
      [image: see text]

PMID- 17195278
TI  - Patients with Lewy body dementia use more resources than those with Alzheimer's
      disease.
AB  - OBJECTIVES: The purpose of this study was to compare resource use and costs in
      patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) and to
      assess determinants of costs of care in DLB. METHOD: Thirty-four patients with
      DLB were included in a cross-sectional study. The patients were matched with
      respect to age, gender and Mini Mental State Examination (MMSE) score to 34
      patients with AD. Both groups were examined using Resource Utilisation in
      Dementia (RUD Lite), MMSE and the Neuropsychiatric inventory (NPI). The DLB
      patients were additionally examined using the Disability Assessment for Dementia
      Scale (DAD). RESULTS: Costs of care in patients suffering from DLB was on average
      348,000 SEK (37,500 euro) per year compared to 169,000 SEK (18,200 euro) in the
      AD group (p < 0.001). Within the DLB group, care costs correlated significantly
      (r(c) = 2.77, p < 0.001) with dependency in instrumental activities of daily
      living measured with DAD, whereas MMSE and NPI were not significantly correlated
      to resource use in the DLB group. CONCLUSIONS: DLB patients use more resources,
      and are more costly than AD patients. Dependency in instrumental activities of
      daily living is strongly correlated to resource use in DLB patients.

PMID- 17195279
TI  - Modelling seasonal and weather dependency of cardiac arrests using the covariate
      order method.
AB  - A data set concerning cardiac arrests treated by the Emergency Medical Service in
      Trondheim during a nine year period is analysed. The relationship between the
      occurrence of cardiac arrest and covariates related to weather and season is
      examined. The covariate order method is used in the analysis of the data. It is
      explained how this method can be extended to recurrent event data, and the
      practical usefulness and flexibility of the method is demonstrated in these
      analyses. In the analyses a significant relationship between outdoor air
      temperature, or factors closely related to outdoor air temperature, and the
      occurrence of cardiac arrest is found. The incidence of cardiac arrest decreases
      with increasing temperature. Further a significant effect of snowfall is also
      found, with increased intensity of cardiac arrest on days with snowfall. A more
      borderline significant effect of precipitation is also identified.

PMID- 17195280
TI  - Open-tubular capillary electrochromatography-mass spectrometry with sheathless
      nanoflow electrospray ionization for analysis of amino acids and peptides.
AB  - A novel, rugged sheathless capillary electrochromatography-electrospray
      ionization (CEC-ESI) device, in which an open-tubular separation capillary and an
      electrospray tip are integrated with a Nafion tubing junction, is coupled to mass
      spectrometry (MS) for the analysis of amino acids and peptides. A stable
      electrospray was generated at nanoflow rates by applying a positive electrical
      potential at the Nafion membrane junction. To sustain the stable spray, an
      electroosmotic flow (EOF) to the spray was supported by coating the fused silica
      capillary with Lupamin, a high-molecular-weight linear positively charged
      polyvinylamine (PVAm) polymer, which also minimizes analyte adsorption.
      Electrochromatographic separation of amino acids and peptides was further
      enhanced by the chromatographic selectivity of Lupamin stationary phase for these
      molecules. The device was very reliable and reproducible for CEC-ESI-MS analyses
      of amino acids and peptides for over a hundred injections. The separation and
      detection behaviors of amino acids and peptides under different conditions
      including pH, concentration, and composition of mobile phases on Lupamin-coated
      and uncoated capillaries have been investigated. The relationship between nano
      electrospray stability and EOF is discussed.

PMID- 17195293
TI  - Current awareness in prenatal diagnosis.

PMID- 17195295
TI  - [Balloon kyphoplasty in the therapy of vertebral fractures].
AB  - Approximately 500,000 vertebral fractures occur as a result of osteoporosis every
      year in Europe. One third of the patients thus affected complain of severe back
      pain and seek treatment. In the past, the treatment of such fractures was limited
      to conservative methods, such as the use of braces and analgesics and long-term
      immobilisation followed by physiotherapy. Since 1998 balloon kyphoplasty, a
      minimally invasive procedure, has also been available for their treatment. During
      balloon kyphoplasty a balloon system is introduced into a fractured vertebral
      body to achieve bitranspedicular augmentation, after which low-viscosity bone
      cement is injected into the vertebral body, where it sets very quickly. In
      general the patient can be fully mobilized 24-48 h after the procedure and in
      most cases the symptoms are then considerably attenuated; many patients are
      actually free of pain. Published studies and our own experience indicate that
      balloon kyphoplasty is a safe method of treating painful vertebral compression
      fractures sustained in various ways and that complications are rare with this
      procedure.

PMID- 17195297
TI  - [Cervical disc prostheses].

PMID- 17195298
TI  - Richard Joseph Mulvaney.

PMID- 17195299
TI  - The sentinel node concept: a critique of the critique.

PMID- 17195300
TI  - A festschrift in honour of Professor John C. Marshall.

PMID- 17195301
TI  - Proceedings of the International Society on Oxygen Transport to Tissue (ISOTT)
      32nd annual meeting, Bari, Italy, August 21-26, 2004.

PMID- 17195302
TI  - Memorial issue for Professor Kenneth L. Rinehart (1929-2005).

PMID- 17195303
TI  - Glucose utilization is suppressed in the gut of insulin-resistant high fat-fed
      rats and is restored by metformin.
AB  - It has been recently suggested that the small intestine (SI) has the capacity to
      contribute to endogenous glucose production (EGP), in addition to the liver and
      kidney. The aim of this work was: (1) to estimate the role of SI glucose fluxes
      in glucose homeostasis in insulin resistance states (induced by high-fat (HF)
      feeding); (2) to assess the effect of metformin, an anti-diabetic molecule, on
      these fluxes. Rats were fed for 6 weeks on a HF-diet, supplemented or not with
      metformin (HF-Met) at a daily dosage of 50 mg/kg during the last week. We
      combined arterio-venous glucose balance measurements and isotopic dilution
      techniques to separate basal intestinal glucose uptake (IGU) and release (IGR).
      Contrary to what was observed in control starch-fed rats, IGU was negligible in
      HF-fed rats: 0.6 +/- 2.4 micromol/kg min (mean +/- S.E.M., n = 9). It was
      restored to a level close to that of control rats in the HF-Met group: 13.0 +/-
      6.7 micromol/kg min (mean +/- S.E.M., n = 9, p < 0.05 compared to the non-treated
      group). Similarly, IGR was close to zero in HF-fed rats (-3.8 +/- 2.6 micromol/kg
      min), but was significant in HF-Met rats (7.4 +/- 4.4 micromol/kg min, p < 0.05
      compared to non-treated rats). These data strongly suggest that the impairment of
      glucose uptake in the SI might be a crucial feature of insulin resistance states
      and that a key beneficial effect of metformin in these situations might be to
      restore a normal glucose metabolism in this tissue.

PMID- 17195304
TI  - Separation-survivability--the elusive moral cut-off point?

PMID- 17195305
TI  - Eculizumab in paroxysmal nocturnal hemoglobinuria.

PMID- 17195306
TI  - Enoxaparin in elective percutaneous coronary intervention.

PMID- 17195307
TI  - Eculizumab in paroxysmal nocturnal hemoglobinuria.

PMID- 17195308
TI  - Mircea Steriade (1924-2006).
AB  - Dr. Mircea Steriade passed away at age 82. In this obituary I briefly describe
      some of the most important achievements of his remarkable life and I express
      deepest sympathies to his family members, collaborators and trainees.

PMID- 17195309
TI  - Enoxaparin in elective percutaneous coronary intervention.

PMID- 17195310
TI  - Enoxaparin in elective percutaneous coronary intervention.

PMID- 17195311
TI  - [Sentinel node mapping in head and neck squamous cell carcinoma].
AB  - BACKGROUND: Commonly used staging procedures often cannot predict the absence of
      lymphatic micro- metastases in squamous cell carcinoma (SCC) of the head and
      neck. Therefore in many cases an elective neck dissection (ND) is necessary. In
      the surgical therapy of melanoma or breast cancer the presence of metastases can
      be evaluated securely by identification and examination of the sentinel lymph
      node (SLN). The type of surgical procedure is usually chosen in regard to the
      histopathological result. The present study evaluates the applicability of this
      concept for SCC of the head and neck. METHODS: Radioactive labeled micro-albumin
      particles were injected preoperatively around the tumor in 38 patients without
      proven metastases. Following the excision of the primary tumor the sentinel lymph
      node/s were detected and dissected and ND was completed. Histological examination
      of the tissue was performed to evaluate whether the SLN reflected the lymphatic
      status. RESULTS: In two cases (5.1 %) no SLN were detected. ND was completed in
      32 cases. In nine cases (28.1 %) the SLN were infiltrated by the primary tumor.
      In 22 cases (68.8 %) SLN and ND revealed a N(0) stage. In one case (3.1 %) we
      could not identify a metastasis because of the anatomical closeness of the SLN to
      the primary. The negative predictive value was 96 %. CONCLUSION: Predictive value
      regarding metastases to the neck was higher with the detection of SLN than with
      conventional staging procedures. Whether the detection of a tumor-free SLN is an
      indication not to perform an elective neck dissection is a matter of discussion,
      especially under the aspect of the effective reduction of postoperative
      morbidity.

PMID- 17195312
TI  - Costing climate change.

PMID- 17195313
TI  - Iceland shunned over whale hunting.

PMID- 17195314
TI  - Gines Morata.

PMID- 17195315
TI  - The use, education, training and supervision of neuropsychological test
      technicians (psychometrists) in clinical practice. Official statement of the
      National Academy of Neuropsychology.

PMID- 17195316
TI  - Brewing controversies: Darwinian perspective on the adaptive and maladaptive
      effects of caffeine and ethanol as dietary autonomic modulators.
AB  - Ethanol and caffeine are two of the oldest human drugs. Their pervasive
      integration into the modern human diet may reflect behavioral attempts to correct
      maladaptations induced by evolutionary displacement of the autonomic system. The
      dietary adoption of caffeine may parallel the emergence of cognition as an
      independent basis of competition. Enhancement of the cognitive ability to gather
      and process information likely evolved as a valuable adjunct to physical behavior
      in prehistoric fight-or-flight encounters. Caffeine effectively exploits this pre
      existing association between adrenergic activity and cognitive readiness, leading
      to its use in the modern environment where success in competition increasingly
      depends on cognitive, rather than physical, prowess. Ethanol may have emerged as
      a dietary means to buffer the maladaptive chronic sympathetic activation and fear
      response associated with stressful lifestyles and the social phobias associated
      with the dissolution of kin networks. We explore the health implications of
      ethanol and caffeine use, with particular attention to their acute and chronic
      effects on the autonomic axis. The putative protective effects of ethanol in
      surviving major trauma or reducing inflammation and heart disease may relate to
      tempering the behavioral and cardiovascular consequences of catastrophic or
      chronic sympathetic activation. Acute or chronic abuse of ethanol manifests
      paradoxical pro-adrenergic effects such as tremors and insomnia that may partly
      represent compensatory responses. Compensatory remodeling may also explain why
      confirmation of detrimental effects related to caffeine-induced sympathetic
      activation has proven elusive; indeed, paradoxical pro-vagal benefits may
      eventually be recognized. Ethanol and caffeine are potential agents that may
      beneficially expand the dynamic range of the autonomic system. In an environment
      where the Darwinian value of knowledge has increasingly supplanted that of
      physical traits, the consumption of caffeine and alcohol may represent both a
      cause and an effect of modern human evolution.

PMID- 17195317
TI  - The dentist down the street.

PMID- 17195318
TI  - Patient outcomes and clinical performance: parallel paths or inextricable links?

PMID- 17195319
TI  - A word of praise.

PMID- 17195320
TI  - [Coma in a child after treatment with the 'magic salve' lidocaine-prilocaine
      cream].

PMID- 17195321
TI  - [Favourable results with surgical treatment in 43 children with hypoplastic left
      heart syndrome or similar disorders, 1999-2005].

PMID- 17195322
TI  - Two areas in urgent need of HIV-related prevention: injection drug use and
      extensively drug-resistant TB.

PMID- 17195323
TI  - HIV-associated Burkitt lymphoma: case presentations and review.

PMID- 17195324
TI  - Images in HIV/AIDS. Pruritic cryptococcal skin lesions in an HIV-positive person.

PMID- 17195325
TI  - Solid organ transplantation: referral, management, and outcomes in HIV-infected
      patients.
AB  - Advances in HIV management make it difficult to deny solid organ transplantation
      to HIV-infected patients based on futility arguments. Preliminary studies suggest
      that both patient and graft survival are similar in HIV-negative and HIV-positive
      transplant recipients. While there has been no significant HIV disease
      progression, substantial interactions between immunosuppressants and
      antiretroviral drugs necessitate careful monitoring. The evaluation and
      management of HIV-infected transplant candidates and recipients require excellent
      communication among a multidisciplinary team, the primary HIV care provider, and
      the patient. Timely referral for transplant evaluation will prevent unnecessary
      mortality during the pre-transplant evaluation process.

PMID- 17195326
TI  - Meningitis with papillitis, choroiditis, and hearing loss: an unusual
      presentation of cryptococcosis in HIV infection.
AB  - Cryptococcosis is a common opportunistic infection in immunosuppressed patients.
      We present a case of cryptococcal meningitis with bilateral papillitis,
      multifocal choroiditis, and sensorineural hearing loss. The ocular manifestations
      present in this patient were unusual. The management of such cases poses a
      challenge because blindness and deafness can be the morbid sequelae.

PMID- 17195327
TI  - HIV-associate mortality in the HAART era.

PMID- 17195328
TI  - An alternative credentialing system for HIV.

PMID- 17195330
TI  - Go ahead, pick your pump. Which pump is right for you?

PMID- 17195329
TI  - Maintaining your health during the holidays.

PMID- 17195331
TI  - Diabetes quiz. How much do you know about storing insulin?

PMID- 17195332
TI  - Eating across America. The Midwest.

PMID- 17195333
TI  - National Diabetes Month. Reviewing the types of diabetes.

PMID- 17195334
TI  - What really determines what we eat. The hidden truth.

PMID- 17195335
TI  - Biking 101.

PMID- 17195337
TI  - Supermarket smarts. Canned and frozen food.

PMID- 17195336
TI  - Choosing and using an insulin pump infusion set.

PMID- 17195338
TI  - Diabetes resources. Food portioning tools.

PMID- 17195339
TI  - Histopathologic study of long-bone growth plates confirms the basset hound as an
      osteochondrodysplastic breed.
AB  - Osteochondrodysplasias are caused by abnormal development and growth of cartilage
      and bone. These abnormalities have been reported in both humans and animals with
      dwarfism. The basset hound is considered a breed with a disproportionate
      prevalence of dwarfism, the cause of which is unknown. To determine the type of
      osteochondrodysplasia in this breed, we analyzed histologically the growth plates
      from the long bones of a basset hound and a Doberman pinscher, both 2 mo old.
      Tissue was fixed in 4% paraformaldehyde, embedded in paraffin, sectioned at 5
      microm, stained with hematoxylin and eosin, and analyzed by light microscopy. Our
      results suggest that by this method the basset hound can be defined only as a
      breed having osteochondrodysplasia due to a primary cartilage problem in the
      growth plate.

PMID- 17195343
TI  - A right to be safe.

PMID- 17195344
TI  - Undergraduate medical education.

PMID- 17195345
TI  - BMI of Australian general practice patients.

PMID- 17195346
TI  - Institutionalizing inequities: black children and child welfare in Cleveland,
      1859-1998.

PMID- 17195347
TI  - [Neonatal resuscitation].
AB  - At birth approximately 10 % of term or near-term neonates require initial
      stabilization maneuvers to establish a cry or regular breathing, maintain a heart
      rate greater than 100 beats per minute (bpm), and good color and muscular tone.
      About 1 % requires ventilation and very few infants receive chest compressions or
      medication. However, birth asphyxia is a worldwide problem and can lead to death
      or serious sequelae. Recently, the European Resuscitation Council (ERC) and the
      International Liaison Committee on Resuscitation (ILCOR) published new guidelines
      on resuscitation at birth. These guidelines review specific questions such as the
      use of air or 100 % oxygen in the delivery room, dose and routes of adrenaline
      delivery, the peripartum management of meconium-stained amniotic fluid, and
      temperature control. Assisted ventilation in preterm infants is briefly
      described. New devices to improve the care of newborn infants, such as the
      laryngeal mask airway or CO2 detectors to confirm tracheal tube placement, are
      also discussed. Significant changes have occurred in some practices and are
      included in this document.

PMID- 17195348
TI  - [Automated external defibrillation in children].
AB  - Ventricular fibrillation is an infrequent arrhythmia in cardiac arrest occurring
      in the out-of-hospital setting in infants and small children. However, outcome is
      good provided early defibrillation is performed; consequently, this procedure is
      one of the main links in the chain of survival in children with a shockable
      rhythm. Automated external defibrillators are small devices that can analyze
      heart rhythm and deliver a dose of electric energy when considered timely by the
      operator. Automated external defibrillators are easy to use and can be operated,
      if necessary, by anyone. Therefore, all pediatricians should be aware of how
      these devices work and be able to use them safely and effectively, following the
      current defibrillation protocol.

PMID- 17195349
TI  - US institute seeks to bridge bench-to-bedside gap.

PMID- 17195350
TI  - [Classification criteria for the antiphospholipid syndrome--the next
      modification].

PMID- 17195351
TI  - [Antiphospholipid syndrome (APS) primary (PAPS) and secondary (SAPS)].
AB  - BACKGROUND: During the last decade, a wide variety of clinical manifestations and
      serological disturbances have been described associated to APS. However the real
      prevalence of most clinical manifestations with several autoantibody-cofactor
      systems still needs precise epidemiological and clinical long-term study.
      OBJECTIVE: Evaluation of frequency clinical and serological symptoms of SLE and
      APS in PAPS and SAPS pts. METHODS: Two groups of pts were analyzed: 78 SAPS
      (76F+2M) and 43 PAPS (32F+11M). All pts met Sapporo criteria for APS and SAPS pts
      met ARA criteria for SLE. Epidemiological, clinical and serological data were
      collected during 1995-2005 in the Connective Tissue Disease, Institute of
      Rheumatology, Warsaw, Poland and modified in 2005 according to actual directive
      line. RESULTS: PAPS pts were younger at the onset of the disease compare to SAPS
      pts. Duration time of the disease to set up the diagnosis as well as observation
      time was shorter in PAPS pts. Separated PAPS pts showed no more than two ARA
      criteria for SLE. All clinical ARA criteria for SLE occurred more often in SAPS
      pts. Also recurrent miscarriages, livedo reticularis and anti AnnexinV abs
      occurred more often in these pts. Pulmonary embolism, deep venous thrombosis and
      IgM aCL, LAC, anti beta2GP1, oxyLDL abs occurred more often in PAPS pts. Arterial
      thrombosis, migraine, crural ulceration, thrombocytopenia, false positive VDRL
      and IgG aCL abs were detected in almost the same percentage in both groups of
      pts. CONCLUSION: Men are less affected with SAPS. Wide variety of clinical SLE
      symptoms and immunological disturbances are more frequent in SAPS pts. Also in
      these pts recurrent miscarriages, livedo reticularis and anti AnnexinV abs occur
      more often. However pulmonary embolism, deep venous thrombosis with LAC, anti
      beta2GP1, IgM aCl, anti oxyLDL occur in less frequency in SAPS pts. The presence
      of arterial thrombosis, migraine, crural ulceration, thrombocytopenia, false
      positive VDRL and aCL IgG were almost in the same percentage in both groups of
      pts. Precise determination of the link between clinical symptoms of the APS and
      antibody-cofactor system needs future study on a bigger sample of pts.

PMID- 17195352
TI  - [Antiphospholipid syndrome and antiphospholipid antibodies as a risk factors of
      ischaemic heart disease and myocardial infarction in patients with systemic lupus
      erythematosus].
AB  - Ischemic heart disease and myocardial infarction in patients with SLE--are
      usually secondary to early coronary atherosclerosis. Estimation if
      antiphospholipid syndrome and antiphospholipid antibodies are the risk factor for
      myocardial infarction and ischemic heart disease in patients with TRU. We
      examined 129 patients with SLE (114 women and 15 men). All the patients underwent
      comprehensive physical examination. ECG, ultrasound heart examinations were
      performed. They were followed by heart scintygraphic examination if indicated.
      Routine biochemical and hematological laboratory tests were performed including
      fasting glucose level, concentration of homocysteine, uric acid and lipids. Wide
      range of immunological essays were performed, testing for antinuclear antibodies
      (ANA), extractable nuclear antigen antibodies (ENA), antiphospholipid antibodies
      (anticardiolipin antibodies--aCL, lupus anticoagulant--LA, antiprothrombine
      antibodies aPT, anti-beta2glicoprotein-I antibodies), anti-dsDNA antibodies, anti
      nucleosome antibodies, antihistone antibodies, antineutrophil cytoplasmic
      antibodies (ANCA) and antiendothelial antibodies (AECA). Statistical analysis was
      performed with chi2 Yates, chi2 Pearson and R rang Spearman tests. Multivariate
      regression analysis was also done. Ischemic heart disease was found in 20 (15.5%)
      SLE patients, myocardial infarctions were diagnosed in 9 (6.97%). Ischemic heart
      disease and myocardial infarction were significantly related to presence of
      secondary antiphospholipid syndrome (SAPS), OR: 4.21, p = 0.008 and OR: 12.8; p =
      0.02 respectively). They were also related to high activity of SLE, OR: 7.18; p =
      0.012 and OR: 27.3; p = 0.006 respectively. Ischemic heart disease was
      significantly more common in older patients (52.75 years versus 42.15 years; p =
      0.0008) and in patients with hypertension (p < 0.05). Impaired glucose tolerance
      (OR: 8.44; p = 0.03), presence of aCL IgG (OR; 2.93; p = 0.05) and p-ANCA anti
      MPO (OR: 6.08; p = 0.036) were found to be risk factors of ischemic heart
      disease. Myocardial infarction was significantly associated with high uric acid
      level (OR: 5.01; p = 0.052) and impaired glucose tolerance (OR: 7.42; p = 0.047)
      and with presence of the following antibodies: aCL IgG and/or aCL IgM (OR: 5.61;
      p = 0.039), ANCA in the indirect immunofluorescence essay (OR: 5.78; p = 0.035),
      anti-MPO antibodies (OR: 6.58; p = 0.051) and AECA (OR: 11.10; p = 0.026).
      Presence of antiphospholipid antibodies and SAPS are significant risk factors of
      ischemic heart disease and myocardial infarction in SLE patients. The risk
      factors of ischemic heart disease and myocardial infarction in SLE patients
      significantly differ from the ones in general population.

PMID- 17195353
TI  - [Prevalence of antiphospholipid antibodies in patients with primary Sjogren's
      syndrome].
AB  - The aim of this study was to determine prevalence of antiphospholipid antibodies
      (aPL) including anticardiolipin antibodies (aCL), and anti-beta2GP1 in a cohort
      of 32 patients with primary Sjogren's syndrome (pSS) diagnosed according to
      revised European criteria. aPL were found in 9/32 (28%) patients (IgG in 8 and
      IgM in one case). Anti-beta2GPI antibodies were detected only in two patients.
      Titres were usually low.

PMID- 17195354
TI  - [Frequency of antiphospholipid antibodies and factor V (G1691A), prothrombin
      (G20210A) gene polimorphism among women with pregnancy complications].
AB  - Thrombophilia these days is a subject of many medical research including
      obstetric and gynecology where causing feto-maternal complications. In women
      predispose to venous thromboembolism in high risk situation like pregnancy,
      puerperium, operation, prolonged bed rest or hormonal treatment. For fetal
      complication account miscarriages, intrauterine deaths, IUGR, and for maternal
      account premature placental separation and severe preeclampsia. Diagnostic panel
      include inherited factors like factor V Leiden and prothrombin mutation,
      activated protein C resistance and acquired like anticardiolipin antibodies,
      antibodies against beta2-glicoprotein 1 and lupus anticoagulant. The aim of this
      paper is estimation ofthrombophilia as a causative factor of pregnancy
      complications and attempt to establish screening criteria for thrombophilia.
      Material involved 36 women with pregnancy complications divided into three groups
      correlating with trimester when pregnancy loss occured. All patients had genetic,
      hormonal and anatomic tests done on purpose to exclude other possible causes of
      miscarriages. All women had done both types of tests for inherited and acquired
      thrombophilia. For factor V and II gene polimorphism we used PCR and RLFP method.
      Acquired protein C resistance and lupus anticoagulant was tested using
      chronometric method with the use of time measurement of optical density
      accompanying coagulation. Anticardiolipin antibodies and antibodies against beta2
      glicoprotien 1 were measured in ELISA tests. Our current results present the
      frequency of at least one thrombophilic factor in 16.6% patients. The highest
      frequency rate was observed among women with pregnancy loss between 7th and 12th
      gestational week--19.04%. In this group we also noticed the highest number of
      miscarriages. In remaining two groups, with pregnancy loss between 12th and 22nd
      and after 22nd gestational week, one case of thrombophilia occurred in each
      group.

PMID- 17195355
TI  - [Relations beetwen severity of anemia and certain antiphospholipid antibodies
      presence in systemic lupus erythematosus patients].
AB  - Anaemia is a common hematological abnormality in systemic lupus erythematosus
      (SLE). Autoimmune hemolytic anaemia (AHA) is one of the types of anaemia in SLE.
      Other reasons of anaemia in SLE are: chronic inflammatory diseases, insufficient
      level of elements necessary for erythropoiesis and chronic renal disease. The aim
      of the study was to examine the relations between severity of anemia and presence
      of certain antiphospholipid antibodies (aPL) in SLE. The study group consisted of
      24 patients (one man and 23 women) with active lupus. Anticardiolipin antibodies
      (aCL), anti-02 glycoprotein I antibodies (anti-beta2 GPI IgM and IgG) and red
      cell parameters: haemoglobin level (Hb), erythrocytes (RBC), mean corpuscular
      volume (MCV), mean corpuscular haemoglobin mass (MCH), mean corpuscular
      haemoglobin concentration (MCHC) and ferritin level were measured before
      beginning or intensification of treatment. The activity of SLE was measured by
      SLEDAI and C3 complements. The patients were divided into two subgroups: subgroup
      with aCL-IgG above 20 u/ml and below 20 u/ml. In patients with aCL-IgG above 20
      u/ml the mean Hb level was lower, and the mean ferritin level was significantly
      higher than in patients with aCL-IgG level below 20 u/ml. We observed a negative,
      significant correlations between Hb and aCL-IgG (p = 0.01; R = -0.47) and between
      Hb and anti-32 GPI IgG (p = 0,0003; R = -0,67) and a negative correlation between
      Hb and activity of SLE estimated by SLEDAI (p = 0.02; R = -0.45) and positive
      between Hb and C3 complement (p = 0.02; R = +0.5). IN CONCLUSION:
      antiphospholipid antibodies presence in patients with SLE can influence the
      severity of anaemia.

PMID- 17195356
TI  - [Antiphospholipid syndrome in autoimmune diseases].
AB  - Classification criteria for antiphospholipid syndrome were first proposed in
      1987, revised in 1999 (Sapporo criteria) and up-dated in 2006. The aim of the
      study was to analyze associations between clinical and laboratory symptoms of
      antiphospholipid syndrome in the group of patients with autoimmune diseases,
      based on recently up-dated classification criteria. 336 patients were enrolled
      into the study, with the majority (n=235) suffering from SLE. Laboratory
      determinations included: lupus anticoagulant (LA), anticardiolipin (aCL) and anti
      beta2-glycoprotein I (abeta2GPI) (both of IgG and IgM class). Clinical and
      laboratory symptoms of antiphospholipid syndrome were quite common among patients
      studied. There was a significant association between laboratory and clinical
      features of antiphospholipid syndrome, according to recently modified
      classification criteria.

PMID- 17195358
TI  - [Antiphospholipid syndrome--interdisciplinary problem].
AB  - Antiphospholipid syndrome (APS) is a systemic autoimmune disorder, where the
      essence of the matter is the existence of antiphospholipid antibodies. The
      typical symptoms of APS are: venous thrombo-embolic disease and artery thrombosis
      in a brain. The authors present 5 patients (2 females and 3 males) at the age of
      36-54 with ischemic stroke and one 26-year-old women with thrombosis of central
      retinal vein caused by APS. In 4 cases in secondary prevention anticoagulant
      (acenocumarol) was used and in 2--antiplatelet drug (aspirin). In 2 cases
      congenital disturbances of coagulation were also discovered. We suggest that in
      ischemic stroke and visual disturbances of not-well-known origin it is useful to
      make examinations concerning APS, as well as congenital thrombophilias.

PMID- 17195357
TI  - [Follow-up studies of rheumatoid arthritis patients with the presence of
      antiphospholipid antibodies].
AB  - The aim of the study was 2 years follow-up observation of clinical course in RA
      patients with the presence of anticardiolipin antibodies (aCL). METHODS: Among
      395 patients with RA hospitalized in the Clinic of Rheumatology from January 2003
      to December 2004 (2 years), in 39 patients with suspicion of antiphopspholipid
      syndrome the aCL antibodies were determined. In 7 cases we confirm the presence
      of aCL antibodies. Patients positive for antiphospholipid antibodies were invited
      to the Clinic on the beginning of 2006 (after 2 years from previous
      hospitalization) to analyze clinical course of disease and to perform laboratory
      examination. RESULTS: In the group of patients with RA positive for
      antiphospholipid antibodies, 3 had active RA with vascular changes. Aggressive
      therapy with disease modifying antirheumatic drugs (DMARDs) and corticosteroids
      caused conversion of anticardiolipin antibodies. Analogically antibiotic therapy
      in 2 patients with concomitant infections (urinary tract, respiratory system)
      caused conversion of aCL antibodies. 1 patient developed blastic coat cell
      lymphoma. 1 patient died because of cardiovascular complications. CONCLUSION:
      Presence of anticardiolipin antibodies can be the indicator of serious prognosis,
      it can predict vasculitis, persistent infections, cardiovascular complications or
      neoplasmatic disease. We suggest that antiphospholipid antibodies should be
      measure in patient with aggressive course of rheumatoid arthritis.

PMID- 17195359
TI  - [Inhibition of cardiolipin binding antibodies from synovial fluids of patients
      with arthritis by endotoxin].
AB  - In the presented study was prooven that aCl antibodies cross-reacting with LPS
      (endotoxin) from arthritic synovial fluids are part of the aPL antibodies pool
      and correlated with presence in joints bacterial cell wall components like LPS
      showing endotoxin presence in synovial fluids and they may be usefull in
      differential diagnosis of the different kind of arthritis and also in explanation
      of their aetiology at all--especially in cases of early, undifferentiated
      arthritis.

PMID- 17195360
TI  - [Preliminary data concerning cross-reacting anticardiolipin antibodies as
      potential inhibiting endotoxin activity factors].
AB  - In analyzed synovial fluids, suspected for endotoxin presence, the presence of
      endotoxin done was proved by LAL-test in 21 synovial fluids /42%/ and in 12 of 20
      /60%/ the presence of endotoxin inhibiting substances /IS/ was proved. Because
      many parameters /like presence CIC, anti-LPS, KDO/ indicates that in the group of
      LAL-negative /IS/ - positive synovial fluids the presence of endotoxin is very
      possible, IS have been removed /by heating to 100 degrees C/ and after that the
      endotoxin activity was shown in about 27% of synovial fluids. Additional analysis
      of the Cohn fraction /prepared by ammonium sulfate precipitation/ confirmed the
      presence in the gamma and alpha and beta fractions a weak IS activity /in a dose
      dependent manner. No IS activity, have been shown yet in the fraction of affinity
      purified aCl antibodies.

PMID- 17195362
TI  - [When to start the long-term anticoagulation if antiphospholipid antibodies are
      present in high concentration--case report of the twin brothers].
AB  - The authors describe the observation of twin brothers with high concentrations of
      antiphospholipid anibodies in both of them, and the clinical manifestation of
      antiphospholipid syndrome (APS) and later systemic lupus erythematosus in first,
      without any clinical signs and symptoms in the other. The literature reports of
      twins with APS were analyzed and the discussion about long-term anticoagulation
      beginning proposed.

PMID- 17195361
TI  - [Severe neurological and obstetrical complications in a patient with
      antiphospholipid syndrome].
AB  - Antiphospholipd syndrome (APS) is a disease characterised by venous and arterial
      thrombosis or recurrent foetal loss, which are associated with antiphospholipid
      antibodies or/and lupus anticoagulant. Clinical symptoms ofAPS are assocciated
      with presence of noninflammatory thrombosis ocluding arteries or venes. Symptoms
      of APS are often very dramatic what can be illustrated by the presented case of
      40 year patient. At the age of 25 after a miscarriage the patient developed
      tetraparesis and motor aphasia in the course of thrombosis in central nervous
      system vessels. In physical examination besides neurological symptoms reticular
      livedo was found on the trunk and limbs. Serological tests have revealed presence
      of high titre of IgG and IgM anticardiolipin antibodies and lupus anticoagulant
      (LA). CT examination revealed hypodensic foci in left parietal lobe, and abnormal
      EEG findings were observed in fronto-temporal leads of left hemisphera of brain.
      At that point the patient did not meet the criteria of connective tissue
      diseases, including lupus. The diagnosis of primary APS was suggested. The
      patient received anti-aggregation treatment and also immunosuppressive drugs
      (azathioprine and prednison) due to progression of neurological manifestations. 3
      years later, the second pregnancy ended in the 27th week with intrauterine fetal
      death. During the 3rd pregnancy, 2 years afterwards, the patient was treated with
      heparin, aspirin and intravenous immunoglobulin. The pregnancy finished with a
      successful delivery at term, the newborn was in good condition. During the
      following pregnancy the symptoms of preeclampsia occurred at 36/37th week but the
      newborn was delivered in a good condition after a caesarean section. At the age
      of 36 patient developed ischemic brain stroke with left-side hemiparesis inspite
      of anti-aggregation and immunosupressive (prednison and azathioprine) treatment.
      At that time homogenic type antinuclear antibodies (ANA) 1:2560, anti-beta2
      glycoprotein antibodies (beta2-GPI), aCL antibodies in medium titer and
      thrombocytopenia were found. The patient was treated with heparin,
      cyclophosphamide and methyloprednisolon intravenously. During rehabilitation
      process gradual improvement of cognitive functions, speech and motorical
      functions was observed. Recently high titre of ANA and recurent thrombocytopenia
      < 100,000/mm3 were present. Maybe during the further follow-up, 14 years after
      the first symptoms of APS, the patient will develop full blown symptoms of SLE.

PMID- 17195363
TI  - [Newborn from mother with antiphospholipid syndrome].

PMID- 17195364
TI  - [The management of central nervous system involvement in the antiphospholipid
      syndrome].

PMID- 17195365
TI  - [Antiphospholipid antibodies and antiphospholipid syndrome in juvenile lupus
      erythematosus].

PMID- 17195366
TI  - [Fetus monitoring of a mother suffering from the antiphospholipid syndrome].

PMID- 17195367
TI  - [Diagnostics of deep vein thrombosis].

PMID- 17195368
TI  - [New insights on disorders of haemostasis in the antiphospholipid syndrome].

PMID- 17195369
TI  - [Results of surgical treatment in patients with neurocytomas of the brain].
AB  - Central neurocytoma (CN) is a rare brain neoplasm which is characterized by
      certain clinical, radiological, and morphological characteristics. This tumor was
      first described in 1982 by J. Hassoun et al. who found neurosecretory granules
      and microtubules while microscopically studying 2 patients with
      oligodendrogliomas of lateral ventricles and concluded that these neoplasms were
      of neuronal origin. Materials and methods. In 1992 to 2004, a total of 84
      patients diagnosed as having CN were treated at the Academician N. N. Burdenko
      Research Institute of Neurosurgery, Russian Academy of Medical Sciences. In most
      cases, the tumor showed a clinical picture as elevated intracranial pressure that
      was detected in 80 (more than 90%) cases. In this series, all neurocytomas were
      located in the ventricles, mainly in the pellucid septal region; tumor
      infiltration of the lateral ventricular ependyma and medullary substance invasion
      into the region of the thalamus and corpus callosum. Computed tomographic scans
      displayed central neurocytomas as space-occupying lesions of mixed
      (heterogeneous) density, which frequently contained single and multiple
      petrificates and cysts. TI-weighted magnetic resonance imaging (MRI) indicated
      that in most cases (n=56, 66%), the intensity of a signal from the tumor was
      mixed and similar to that of the white matter of the brain. These masses were
      characterized by the presence of tumor structural cysts that were better
      visualized on T2-weighted tomograms. The tumor was removed in 83 cases; 2 out of
      them had previously undergone stereotactic biopsy (STB). STB was performed alone
      in one case. Transcallous, transcortical-through-premotor-area, combined, and
      transcallous-transcortical approaches were applied when the neurocytomas were
      removed. Results. Total removal of a tumor (when its remains were not visualized
      by postoperative MRI) was achieved in 11 (13%) patients. Its subtotal removal was
      accomplished in 48 (58%) patients. Partial removal was done in 24 (29%) patients.
      In the early postoperative period after tumor removal, there was a worse health
      status along with a transient progression of cerebral and focal symptoms in most
      patients with CN. The magnitude, pattern, and duration of these changes differed.
      Conclusion. The long (from several months to several years) history of the
      disease and young age (14 to 59 years) are typical of patients with CN. The
      tumors are located intraventricularly, more commonly along the midline, and they
      have well-defined X-ray signs: these are well-circumscribed tumors of
      heterogeneous density, which frequently contain single and/or multiple cysts and
      petrificates; there is a moderate contrast enhancement. The basic way of
      improving the results of treatment in patients with CN is the latter's early
      diagnosis and surgery when the tumor is locally advanced within the ventricular
      system.

PMID- 17195370
TI  - [Results of radical removal of malignant cerebral gliomas, by using computer
      assisted navigation, followed by adjuvant therapy].
AB  - A retrospective cohort analysis of the results of treatment of patients with
      malignant gliomas was made in 2 groups, each comprising 43 patients. In Group 1,
      the tumors were radically removed under neuronavigation guidance ("Voyager SX").
      In Group 2 where the patients were operated on by the same team of surgeons who
      did not employ computer-assisted navigation technologies. The results of
      different adjuvant therapy regimens were analyzed in patients after radical tumor
      removal under navigation guidance (Group 1). In its first subgroup, 24 patients
      with anaplastic astrocytes were postoperatively irradiated (60 Gy), followed by
      treatment with temodal (200 mg/m2 (mean 6 courses). In the second subgroup, 12
      patients received chemoradiotherapy (temodal, 75 mg/m2 daily + irradiation),
      followed by courses (n=6) of temodal, 200 mg/m2). In the third subgroup, 7
      patients were treated with fotemustin (200 mg/m2 (induction) + 5 cycles). The
      computer-assisted technologies substantially improve a postoperative outcome in
      patients with malignant glionas. Current chemoradiotherapy is relatively safe and
      prolongs a relapse-free interval with a high quality of life. Further studies
      call for the efficiency of different adjuvant therapy regimens after radical
      surgery.

PMID- 17195371
TI  - [Radical surgical tactics in the treatment of patients with intramedullary
      neoplasms inducing severe neurological deficit. What can we find in this?].
AB  - BACKGROUND: Radical surgery for intramedullary spinal cord tumors (IMSCT) is
      currently accepted as a first-line treatment. At the same time most papers
      concerning this problem show that surgical results depend on the preoperative
      neurological status of a patient. Many authors consider that the functional
      status of a patient with severe neurological deficit does not change for the
      better. MATERIALS AND METHODS: In 2002-2006, at the Academician N. N. Burdenko
      Research Institute of Neurosurgery, the author operated on 63 patients diagnosed
      as having IMSCT as evidenced by magnetic resonance imaging (MRI). Among them,
      there were 29 patients with severe preoperative neurological deficit (3-4 scores
      by the McCormick scale (MCS)). Thirteen (45%) tumors were totally removed; in the
      remaining patients with diffuse tumors, tumor removal was subtotal (more than 80%
      of a tumor being removed, as confirmed by MRI scans). There were neither
      neurological status deteriorations, nor fatal outcomes. Nineteen patients were
      found to have functional improvement by 1-3 MCS scores. Out of them, 15 (52%)
      patients became completely independent in their everyday activities due to
      surgery. CONCLUSIONS: In this series of patients with IMSCT and severe
      preoperative neurological deficit, tumor removal led to functional improvement in
      the patient and his independence in everyday life in 52% of cases. Radical
      surgery for localized IMSCT does not deteriorate the patients' functional status.

PMID- 17195372
TI  - [Rupture of the dissecting vertebral arterial aneurysm].
AB  - The paper describes a rare case of a patient with dissecting vertebral arterial
      aneurysmal rupture. The patient was operated on--the aneurysmal wall was
      reinforced with surgical gauze. The intraoperative signs of the dissecting
      aneurysm are described in detail. The angiographic signs of dissecting aneurysms
      are given.

PMID- 17195373
TI  - [Tactics of surgical treatment for an inflammatory process of C0-C(I)-C(II)
      segments in the craniovertebral joint instability].
AB  - Pathological processes of C0-C(I)-C(II) segments, such as the clivus, atlas arch,
      dens, and body of the C, vertebra pose major problems for diagnosis and
      treatment. On removal of a sizable pathological focus, there may be instability
      of the craniovertebral segment, secondary displacement, and spinal compression
      syndrome. Therefore these patients frequently need stabilization of the
      craniovertebral transition. Patients with initial instability of the
      craniovertebral junction and subluxation of C(I)-C(II) segments are an intricate
      problem. The authors describe a rare case of an inflammatory process of C0-C(I)
      C(II) segments with craniovertebtal junction instability. A differential
      diagnosis was made between chordoma, osteoblastoma, and an inflammatory focus at
      the above site. The following tactics was undertaken: the first stage was
      occipitospondylosynthesis with "Vertex" system with osteoplasty under Halo
      traction; the second stage included transoral removal of a pathological removal
      of the dens and body of the C(II) vertebra, left lateral mass of the CI vertebra,
      and lower clivus. After removal of the pathological focus, there were portions of
      the abnormally changed bone with rarefaction without tumor tissue. Histologic
      studies revealed the signs of a chronic inflammatory process. A five-month follow
      up showed that neurological symptoms and craniovertebral junction instability
      regressed. The control computed tomography made 5 months after surgery
      demonstrated the radical elimination of the pathology and the absence of C,
      vertebral subluxation. Thus, there is evidence for the tactics of successive
      operations (a stabilizing operation--posterior occipitospondylosynthesis
      (desirably under Halo-traction), followed by removal of a pathological focus via
      transoral access) in pathological processes of the craniovertebral C0-C(I)-C(II)
      in cases of initial craniovertebral junction instability.

PMID- 17195374
TI  - [A rating scale and therapeutic strategy in dysphagia in patients with brain stem
      damage].
AB  - Dysphagia appears in 15-17% of cases after removal of tumors of the posterior
      cranial fossa (PCF), which is one of the most life-threatening postoperative
      complications due to a risk of acute airway patency impairment, possible
      aspiration, bronchopulmonary infectious complications. This makes prognosis
      workse and complicates a patient's rehabilitation. Based on the results of
      fibrolaryngotracheoscopic study and treatment of 1653 patients operated on for
      PCF tumors, the authors have developed a scale for rating the severity of bulbar
      disorders. The proposed scale promotes decision making on the expediency of
      performing tracheostomy and on the necessity of evaluating the efficiency of
      performed therapy (trends in bulbar disorders) and predicting the course of a
      postoperative period.

PMID- 17195376
TI  - [Some problems in the organization of neurosurgical care in the Russian
      Federation under division of powers between the levels of authority].

PMID- 17195375
TI  - [The problem of deep vein thrombosis and pulmonary thromboembolism in
      neurosurgical patients].

PMID- 17195377
TI  - Tackling the stigma of HIV.

PMID- 17195378
TI  - Think your way out.
AB  - Nurses in Glasgow are offering 'life skills' courses in further education
      colleges to teach cognitive behavioural therapy (CBT) to the public and other
      teachers. The approach addresses the perceived stigma of seeking help for mental
      health problems as well as the shortage of people trained in CBT.

PMID- 17195379
TI  - Because we're worth it.
AB  - Charities have been putting together evidence about the value and cost
      effectiveness of nurse specialists in an attempt to protect these important posts
      from being cut.

PMID- 17195380
TI  - Disability equality is now compulsory.

PMID- 17195381
TI  - All the health planning was worth it.

PMID- 17195382
TI  - Reflections on nurse independent prescribing in the hospital setting.
AB  - This article focuses on the experiences of nurses undertaking nurse independent
      prescribing in the hospital setting. The challenges and benefits are examined
      using the reflections of those involved in this initiative.

PMID- 17195383
TI  - Clinical decision-making in cardiac nursing: a review of the literature.
AB  - Clinical decision-making is an integral part of the professional nurse's role.
      This literature review aims to determine the present evidence available on
      clinical decision-making in cardiac nursing and to determine implications for
      practice and future research in this field.

PMID- 17195385
TI  - Acute abdominal pain assessment.

PMID- 17195384
TI  - Primary angioplasty for acute ST-elevation myocardial infarction.
AB  - This article examines primary percutaneous coronary intervention as a reperfusion
      treatment for acute ST-segment elevation myocardial infarction. It discusses the
      nursing care of patients undergoing this procedure.

PMID- 17195386
TI  - Don't take it personally.

PMID- 17195387
TI  - How IT is shaping up.

PMID- 17195388
TI  - Pioneering spirit.

PMID- 17195389
TI  - The Amish way. Coping with tragedy.

PMID- 17195390
TI  - Self-harm a Western problem?

PMID- 17195391
TI  - Financial independence linked to recovery.

PMID- 17195392
TI  - Pharmacotherapy for psychotic depression.

PMID- 17195393
TI  - Update on conduct disorder.

PMID- 17195394
TI  - Consumer-operated self-help services.
AB  - To create a mental health system focused on recovery, consumer-operated services,
      for which an evidence base is emerging, should be promoted. Consumer-operated
      services have become a viable, cost-effective model designed to provide social
      support and recovery opportunities for people diagnosed with a psychiatric
      disability who are living in the community. This article describes the consumer
      operated services model and uses a self-help center as an example. The core
      components of consumer-operated self-help centers are outlined. Qualitative data
      gathered through a larger study of self-help centers is presented. The article
      highlights the benefits of and areas for improving this innovative resource,
      which offers many advantages and opportunities for people living with a
      psychiatric disability in the community.

PMID- 17195395
TI  - Nurse-patient advocacy and the right to die.
AB  - This article examines the implications of the U.S. Supreme Court's decision to
      uphold Oregon's Death with Dignity Act, as well as three crucial cases, on
      nursing practice: Terri Schiavo, Karen Quinlan, and Nancy Cruzan. In addition, an
      individual example is provided to demonstrate how nurses can advocate for
      patients at the end of life, and specific suggestions are offered.

PMID- 17195396
TI  - Staying alive! A suicide prevention overview.

PMID- 17195397
TI  - [Evaluation of therapeutics in psychiatry: clinical trials and evaluation of
      psychotherapies].
AB  - Clinical trial methodology is well established in the field of somatic disorders,
      but what about psychiatric treatments? The situation is relatively clear in the
      case of psychotropics but opinions diverge when it comes to psychotherapeutic
      approaches. The author considers four key methodological issues in this setting.
      What are the treatments to be compared? Which patients should be enrolled? How to
      evaluate treatment effectiveness? and how to ensure the treatment groups are
      comparable? The evaluation of treatments used in psychiatry, whether drug-based
      or psychotherapeutic, should follow a methodology very similar to that used for
      somatic diseases. Particularly strong similarities exist with the approaches used
      to evaluate surgical treatments.

PMID- 17195398
TI  - [Psychotropic drug use in France: changes over time and comparison with other
      European countries].
AB  - Over the past 20 years, hypnotic drug use has diminished in France, while
      consumption of anxiolytics and neuroleptics has remained stable and
      antidepressant use has risen. Data from the ESEMeD survey (European Study of
      Epidemiology of Mental Disorders) conducted in 2002 in Germany, Belgium, Spain,
      France, Netherlands and Italy showed that use of anxiolytics during the previous
      year (including recurrent use) was less frequent in Germany than elsewhere.
      Belgium and France had a higher prevalence of antidepressant consumption. Among
      depressed patients, fewer than one-third reported antidepressant use (no
      difference among the countries), while one-third said they used anxiolytics
      (higher rate in France). One-quarter of patients with anxiety stated they used a
      benzodiazepine (lower rate in Germany). Age, psychiatric disorders and
      neurological disorders were strongly associated with benzodiazepine use. Factors
      strongly associated with antidepressant use were age (bell-shaped curve), female
      sex, and psychiatric disorders.

PMID- 17195400
TI  - [Obligatory treatment: ethical, medical and legal issues].
AB  - Legislation passed on 30 June 1838 created a medico-administrative and legal
      framework for forced hospitalization. Updated in 1990, this law has been
      evaluated twice. The last evaluation, in 2005, recommended a 72-hour observation
      period before deciding whether hospitalization was necessary. The situation of
      violent patients remains unclear. On the one hand, the psychiatrist has no means
      of impinging on these patients if they decide to stop their treatment once
      outside the hospital. On the other hand, for patients who are declared to be
      irresponsible, it would be wise to consider the possibility of being able to
      judge them, and adapt their sentences accordingly.

PMID- 17195399
TI  - [Obligation of care: legal, ethical and medical aspects].
AB  - Enforced treatment is a notion that clearly conflicts with the rights of the
      individual, and a balance must be struck with the interests of society. Enforced
      treatment has a very broad legal definition, and may be ordered for a variety of
      crimes and at all stages of the legal procedure. There is also a delicate balance
      between incitation and coercion in this setting. The execution of such orders
      comes up against issues of professional confidentiality (judicial and medical)
      and the delicate question of "certificates of convenience". More cooperation is
      needed between the medical and legal professions, and the roles of each must be
      better defined, as any loopholes may be exploited.

PMID- 17195401
TI  - [Attention deficit with hyperactivity].
AB  - The author presents current conceptions of attention-deficit/hyperactivity
      disorder and discusses available treatments

PMID- 17195402
TI  - [Psychiatric disorders in non demented elderly people].
AB  - Psychogeriatrics is a rapidly growing field. In France, the focus is currently on
      targeted education and specific management. Psychiatric disorders may be atypical
      in the elderly, and may also be difficult to distinguish from the effects of
      aging or somatic disorders. The principal disorders observed in old age are
      depression, late delusion, anxiety disorder, hysteria, delirium and mania.
      Depression has specific features, depressive equivalents, particular risk
      factors, and a categorical and dimensional therapeutic approach. Diagnosis and
      screening must be improved Late delusion is organized around a notion of injury,
      and is an active attempt to deal with isolation, depression and anxiety. The term
      "very late-onset schizophrenia-like psychosis" has been proposed. Anxiety also
      has specific features in the elderly and is intimately related to depression. If
      left untreated, the consequences can be severe. Hysteria is pathoplastic with
      time, age and educational status. Pseudocognitive conversions are starting to be
      seen in old age. Delirium is very frequent in the elderly; it is often
      multifactorial, but psychosocial factors must not be underestimated. Mania can
      also be provoked by somatic disease, and mixed syndromes are far from rare.
      Dementia can be approached from its psychopathological dimension, particularly in
      terms of psychosocial risk factors and protective factors relating to the
      individual's biography and personality. Thus, psychogeriatrics is an integrated
      medical discipline in which psychiatric disorders are approached through specific
      clinical management, oriented research and structured training.

PMID- 17195403
TI  - [Air cleanliness in operating rooms: on-site controls and biological testing].
AB  - Air cleanliness control in operating rooms is based on air filtration, and
      targets the lowest density of particules and bacteria. Legally, the equipment
      must be periodically verified during periods of inactivity. Most airborne
      bacteria are of human origin. There is no fixed ratio between the particle count
      and the level of bacterial contamination. A study of different types of operating
      room at Besancon Medical Center reached the following conclusions:--Controls are
      also required during periods of activity.--Bacteriological testing is crucial.-
      Unidirectional airflow, especially of the horizontal type, is superior to other
      forms of isolation. The authors propose a "Functionality index", calculated as
      follows: bacterial count during use of the room minus bacterial count during non
      use/the number of people in the room. Efficient equipment would have a low index,
      which would be unmodified by the number of persons present.

PMID- 17195404
TI  - [Iatrogenic vascular injuries].
AB  - Seventy-eight iatrogenic vascular injuries were studied from 1970 to 2003. The
      sex ratio was close to 1, and the mean age was 45.7 +/- 24.9 years. The injuries
      mainly involved the femoral vessels in the inguinal region, and occurred during
      radiological investigations, endovascular surgery, or emergency resuscitation.
      The symptoms were acute (hemorrhagic or ischaemic) in half the cases and subacute
      or chronic in the other cases. Arterial repair was possible in 76% of cases.
      There were four deaths (5%). The combined morbidity and mortality rate was 20%,
      reflecting the severity of the lesions. The frequency of iatrogenic vascular
      injuries varied according to the type of medical or surgical procedure:
      laparoscopic surgery and arthroscopic surgery of the knee were especially at
      risk. Late diagnosis was a gravity factor. Repair of the injured vessel is always
      preferable.

PMID- 17195405
TI  - [Arrhythmia-induced dilated cardiomyopathies].
AB  - Arrhythmic cardiomyopathies are due to ventricular dysfunction following
      prolonged or chronic tachycardia; the clinical pictures one of congestive heart
      failure, which is totally reversible after the treatment of tachycardia and the
      restoration of sinus rhythm. Since Whipple's first description of this model of
      heart failure, several teams have shown that ventricular or atrial pacing at
      rates exceeding 220 beats per minute produces a profound and largely reversible
      depression of ventricular function, and a constellation of neuroendocrine
      abnormalities and metabolic, electrophysiological and anatomic alterations of the
      myocardium. The associated heart failure generally starts to improve within days
      of achieving ventricular rhythm control, but clinical recovery may take several
      weeks or months. All forms of chronic tachycardia may induce heart failure, but
      the onset of cardiomyopathy depends more on the heart rate and the duration of
      the arrhythmia than on its type. The pathophysiological mechanisms are multiple
      and complex, and include abnormalities in the structure and function of
      cardiomyocytes and disturbances in excitation-contraction coupling. Treatment
      consists of restoring and maintaining sinus rhythm, or at least of controlling
      the ventricular rate. Because of its curative effect, selective radiofrequency
      ablation is the treatment of choice when the arrhythmogenic substrate is
      localized. Control of the ventricular rate by radiofrequency modification of
      atrioventricular conduction is the treatment of choice for chronic atrial
      fibrillation.

PMID- 17195406
TI  - Can anticyclic citrullinated peptide antibodies be used to successfully monitor
      treatment in rheumatoid arthritis patients?

PMID- 17195407
TI  - Vitamin K and hemorrhagic disease of newborns.

PMID- 17195408
TI  - Hypertensive men living in a southern city: is it a recipe for disaster?

PMID- 17195409
TI  - Role of total thyroidectomy in the treatment of thyroid diseases.

PMID- 17195410
TI  - Occupational and nonoccupational causes of bladder cancer.

PMID- 17195411
TI  - "Silent" giant cell arteritis.

PMID- 17195412
TI  - The macroprolactinemia problem and its solution.

PMID- 17195413
TI  - Solving the mystery of blood pressure in acute stroke.

PMID- 17195414
TI  - Impact of treatment with infliximab on anticyclic citrullinated peptide antibody
      and rheumatoid factor in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the impact of infliximab treatment on anticyclic
      citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) levels in
      patients with rheumatoid arthritis (RA). METHODS: Sera from 33 RA patients
      receiving infliximab and disease modifying antirheumatic drugs were tested for
      anti-CCP antibody, IgA-, IgG- and IgM-RF using a commercially available
      semiquantitative ELISA at baseline, 30 and 54 weeks after treatment. RESULTS: The
      serum levels of anti-CCP antibody and IgA-RF decreased significantly after 30
      weeks (P = 0.002 and 0.024); however, the decrease was not significant at week 54
      (P = 0.147 and 0.207). The decrease in IgG-RF level was not significant at 30 and
      54 weeks (P = 0.059 and 0.097). IgM-RF levels, however decreased significantly at
      30 and 54 weeks (P = 0.002 and 0.004). A strong correlation between anti-CCP and
      IgA-, IgG- and IgM-RF was observed at baseline (r(s) = 0.48, 0.43, 0.65, P = <
      0.05) and after infliximab treatment at 30 (r(s) = 0.45, 0.46, 0.62, P = < 0.05)
      and 54 (r(s) = 0.49, 0.45, 0.60, P = < 0.05) weeks. CONCLUSION: Treatment with
      infliximab results in decreased anti-CCP antibody and IgA-RF early in the course
      of therapy that is not sustained. IgM-RF declines and remains decreased for at
      least 54 weeks. Investigations in larger cohorts of RA patients (especially early
      RA) with longer follow-up are needed to assess the impact of specific therapeutic
      interventions on anti-CCP antibody and RF levels and the relationship of their
      levels to disease activity.

PMID- 17195415
TI  - Intracerebral hemorrhage due to hemorrhagic disease of the newborn and failure to
      administer vitamin K at birth.
AB  - In infants, intracerebral hemorrhage (ICH) is most likely the result of trauma or
      disturbances of coagulation function. Routine and standard care of the newborn
      includes the administration of vitamin K to prevent hemorrhagic disease of the
      newborn. We present two infants, the products of home deliveries, who did not
      receive vitamin K at birth. Both infants developed ICH at 5 weeks of age and
      presented with signs and symptoms of increased IC pressure. In both cases,
      recombinant factor VIIa was administered to correct coagulation function and
      allow immediate surgical intervention which included craniotomy and hematoma
      evacuation in one patient and placement of a ventriculostomy in the other to
      treat increased IC pressure. Despite this therapy, both infants were left with
      severe neurologic sequelae. These two cases illustrate that hemorrhagic disease
      of the newborn can occur when prophylactic vitamin K is not administered and that
      it can have devastating consequences. Given these issues, the routine
      administration of vitamin K to all infants is mandatory and should not be
      considered optional.

PMID- 17195416
TI  - Rural-urban differences in factors associated with poor blood pressure control
      among outpatients.
AB  - BACKGROUND: The purpose of this study was to determine which patient-related
      factors are most strongly associated with having uncontrolled hypertension among
      outpatients. METHODS: A sample of 300 outpatients with diagnosed hypertension
      from three different settings was reviewed, focusing on demographics,
      comorbidity, adherence, and treatment factors. Regression analyses were conducted
      to determine which factors were associated with poor BP control (> 140 mmHg
      systolic or > 90 mmHg diastolic). RESULTS: Those most strongly associated with
      blood pressure control were men (OR 2.04, 95% CI 1.17-3.55) living in a rural
      setting (OR 0.30, 95% CI 0.16-0.55). Age, race, total number of medicines, number
      of visits, and the number of comorbidities were not significantly associated with
      poor blood pressure control in this population. CONCLUSIONS: Being urban and male
      are strongly associated with uncontrolled hypertension. Public health blood
      pressure control efforts in the Southeast region should be directed toward this
      population.

PMID- 17195417
TI  - Total thyroidectomy for the treatment of thyroid diseases in an endemic area.
AB  - INTRODUCTION: Thyroidectomy is a common operation with very low mortality and an
      acceptable morbidity rate. Total thyroidectomy has become the predominant type of
      surgery used today for the treatment of thyroid diseases. In this retrospective
      study, we analyzed the complications of thyroid surgery according to the
      operative technique used in our department. MATERIAL AND METHODS: A retrospective
      analysis was performed for all patients who underwent thyroid surgery during the
      previous 11 years. The period under study was divided into two sections: phase A
      (1995-1999) and phase B (2000-2005). Patient characteristics, type of operation,
      histologic diagnoses and postoperative complications were compared in the two
      study periods according to the type of surgery. RESULTS: A total of 264 patients
      between the ages of 18 and 89 underwent thyroid surgery during the study period
      (133 in phase A and 131 in phase B). Overall histopathological diagnoses were
      nodular goiter (54.9%), hyperplastic nodules (14.7%), adenoma (8.3%), thyroid
      cancer (18.2%), and Hashimoto thyroiditis (3.8%). Total thyroidectomy was
      performed in 91 patients in phase A versus 115 patients in phase B (P < 0.001),
      whereas the use of subtotal thyroidectomy and lobectomy decreased over time. A
      trend toward increased morbidity was noted in phase B. Seven patients had
      hypocalcemia in phase A, whereas 11 patients had hypocalcemia in phase B.
      Similarly, 5 patients had some degree of vocal cord paralysis in phase A,
      compared with 7 in phase B (P > 0.05). Morbidity was significantly increased in
      the case of cancer or reoperation. CONCLUSION: Despite the slightly higher risk
      of complication associated with total thyroidectomy, this has gradually replaced
      more conservative approaches for the treatment of both benign and malignant
      thyroid diseases. Reoperations and surgery for thyroid cancer carried a higher
      risk of complications.

PMID- 17195418
TI  - Overuse of antihypertensives in patients with acute ischemic stroke.
AB  - BACKGROUND: The Stroke Council of the American Heart Association/American Stroke
      Association (AHA/ASA) recommends conservative management of hypertension (HTN)
      during acute ischemic stroke (AIS), although clinicians often manage blood
      pressure more aggressively. Our hypothesis was that aggressive management of HTN
      in patients with AIS is associated with hypotensive events and worsened
      neurologic outcomes. METHODS: The study was a retrospective, observational cohort
      of patients who were admitted to the hospital with AIS. Classification of
      neurologic outcomes was based on nurses' neurologic assessments and were
      categorized as "worsened," "stayed the same," or "improved." The accuracy of
      these assessments was verified by review of physician's progress notes.
      Management of arterial HTN was recorded in all patients. RESULTS: Fifty medical
      records of patients with AIS who met inclusion criteria were reviewed. While only
      22% of patients met the AHA/ASA criteria for hypertension treatment, 98% of the
      cohort were given antihypertensive therapy. Relative hypotension occurred in 64%
      of treated patients. Absolute hypotension associated with antihypertensive
      medications was uncommon but did occur in 2 of 15 patients who experienced
      neurologic worsening (13%), in 1 of 28 (3%) of patients who stayed the same, and
      in none of those who improved. Blood pressure was reduced excessively in all 11
      of the patients who met AHA/ASA guidelines for treatment. CONCLUSIONS: Adherence
      to AHA/ASA guidelines for HTN management during AIS was poor. Initiation or
      intensification of antihypertensive drugs was not associated with worsened
      neurologic outcomes. Furthermore, relative hypotension, absolute hypotension and
      excessive reductions in blood pressure were not associated with worsened
      neurologic outcomes.

PMID- 17195419
TI  - Irritable bowel syndrome: a practical review.
AB  - The epidemiology and current understanding of the pathophysiology of irritable
      bowel syndrome is reviewed, beginning with a historical perspective. The roles of
      genetics, environment, allergy, infection and inflammation, bacterial overgrowth,
      hormones and motility abnormalities are discussed. Using the current evidence
      based literature, the practical approach of diagnosis and treatment is outlined,
      including traditional modalities and newer therapeutic agents such as serotonin
      modulators.

PMID- 17195420
TI  - Opioids for chronic nonterminal pain.
AB  - This article first reviews the evidence for and against chronic opioid therapy.
      Evidence supporting the opioid responsiveness of chronic pain, including
      neuropathic pain, includes multiple randomized trials conducted over months (up
      to 8 months). Observational studies are conducted for longer, and many also
      support opioid analgesic efficacy. Concerns have arisen about loss of efficacy
      with prolonged use, possibly related to tolerance or opioid-induced hyperalgesia.
      Mechanisms of tolerance and opioid-induced hyperalgesia are explored. Evidence on
      other important outcomes such as improvement in function and quality of life is
      mixed, and is less convincing than evidence supporting analgesic efficacy. It is
      clear from current evidence that many patients abandon chronic opioid therapy
      because of the unacceptability of side effects. There are also concerns about
      toxicity, especially when opioids are used in high doses for prolonged periods,
      related to hormonal and immune function. The issue of addiction during opioid
      treatment of chronic pain is also explored. Addiction issues present many complex
      questions that have not been satisfactorily answered. Opioid treatment of pain
      has been, and remains, severely hampered because of actual and legal constraints
      related to addiction risk. Pain advocacy has focused on placing addiction risk
      into context so that addiction fears do not compromise effective treatment of
      pain. On the other hand, denying addiction risk during opioid treatment of
      chronic pain has not been helpful in terms of providing physicians with the tools
      needed for safe chronic opioid therapy. Here, a structured goal-directed approach
      to chronic opioid treatment is suggested; this aims to select and monitor
      patients carefully, and wean therapy if treatment goals are not reached. Chronic
      opioid therapy for pain has not been a universal success since it was re
      established during the last two decades of the twentieth century. It is now
      realized that the therapy is not as effective or as free from addiction risk as
      was once thought. Knowing this, many ethical dilemmas arise, especially in
      relation to patients' right to treatment competing with physicians' need to offer
      the treatment selectively. In the future, we must learn how to select patients
      for this therapy who are likely to achieve improvement in pain, function and
      quality of life without interference from addiction. Efforts will also be made in
      the laboratory to identify opioids with lower abuse potential.

PMID- 17195421
TI  - An updated review of the literature: risk factors for bladder cancer with focus
      on occupational exposures.
AB  - Workplace exposures account for 5 to 25% of all bladder cancer cases. A critical
      review of the literature between 1938 and 2004 was performed, with a focus on
      occupational exposures. Occupational exposure to bladder carcinogens,
      particularly to beta-naphthylamine occur in a number of industries, including
      aromatic amine manufacture, rubber and cable manufacture, and dyestuff
      manufacture and use. Risks to workers in a number of new occupations and
      industries are reviewed. Nonoccupational risk factors that are known or at one
      time have been thought to increase the risk of bladder cancer are also discussed.

PMID- 17195422
TI  - Minimal change disease: a review.
AB  - Minimal change disease (MCD) is a histopathological lesion in the kidney that is
      most commonly associated with nephrotic syndrome. The majority of the cases are
      idiopathic. Pathogenesis is not well understood, although T-cell-related
      mechanisms are implicated. Massive proteinuria leads to hypoalbuminemia, salt
      retention, disorder of hemostasis, hyperlipidemia and increased susceptibility to
      infections. Renal biopsy remains the gold standard for diagnosis. MCD is highly
      responsive to corticosteroids. Other immunosuppressive agents such as
      cyclophosphamide, cyclosporin, azathioprine and mycophenolate mofetil have been
      used to treat cases which are resistant to steroids.

PMID- 17195423
TI  - Exenatide: a novel approach for treatment of type 2 diabetes.
AB  - Exenatide (synthetic exendin-4) is the analog of glucagon-like peptide 1 (GLP-1),
      the major physiologic incretin. The latter is an intestinal hormone that enhances
      glucose-induced insulin secretion after meals. In addition, GLP-1 stimulates
      insulin synthesis, inhibits glucagon secretion, delays gastric emptying, and may
      promote satiety. These glucoregulatory actions help control plasma glucose in the
      postprandial period. However, in diabetes, the GLP-1 response to nutrient intake
      is impaired, leading to exacerbation of postprandial hyperglycemia. Exenatide was
      recently approved as adjunctive therapy in diabetic patients failing
      sulfonylureas and/or metformin. In clinical trials lasting 30 weeks, exenatide
      therapy was associated with moderate reduction in mean hemoglobin A1c (HbA1c)
      levels of approximately 0.8%, and an average weight loss of approximately 2 kg
      compared with baseline. Hypoglycemia was generally mild and occurred more
      commonly when exenatide was used in conjunction with sulfonylureas. The
      requirement of subcutaneous injections twice a day, and the frequent occurrence
      of nausea and vomiting, represent the main limitations of exenatide.
      Nevertheless, this agent may be a useful add-on therapy in obese diabetic
      patients with suboptimal control as a result of continuing weight gain and/or
      severe postprandial hyperglycemia. The introduction of GLP-1-based antidiabetic
      drugs is a novel and promising strategy to treat diabetes.

PMID- 17195424
TI  - Giant cell arteritis mimicking multiple myeloma; diagnosed by PET scan.
AB  - This case report describes a patient who presented with severe anemia, monoclonal
      gammopathy, a high erythrocyte sedimentation rate and significant weight loss.
      These features were highly suggestive of multiple myeloma. Bone marrow aspiration
      was negative for myeloma on two occasions. A positron emission tomography (PET)
      scan showed extensive 2-flourodeoxy-glucose uptake in the vascular tree
      consistent with arteritis. A temporal artery biopsy established the diagnosis of
      giant cell arteritis (GCA). There were no typical symptoms of GCA, such as
      headache, visual disturbance, or polymyalgia rheumatica. The patient was treated
      with steroids, which resulted in the resolution of anemia, monoclonal gammapathy,
      and other symptoms.

PMID- 17195425
TI  - Macroprolactinemia in a patient with infertility and hyperprolactinemia.
AB  - A significant number of patients with hyperprolactinemia have macroprolactinemia,
      a condition characterized by the preponderance of big-big prolactin with normal
      levels of free prolactin. As macroprolactin does not have biologic activity, such
      patients do not require further investigations or treatment for
      hyperprolactinemia. The case of a patient with hyperprolactinemia diagnosed
      during investigation of secondary infertility is presented. She was treated for
      over 2 years with dopamine agonists, with which her prolactin level normalized,
      but she remained infertile. Subsequent investigations demonstrated that she
      suffered from macroprolactinemia, not true hyperprolactinemia. The patient is
      currently not on dopamine agonist therapy, and although her total prolactin
      levels remain significantly elevated, her free prolactin levels have been in the
      normal range. Physicians should familiarize themselves with this entity and
      consider testing for it in patients with hyperprolactinemia to avoid an
      inappropriate diagnosis and unnecessary treatment.

PMID- 17195426
TI  - Extraprostatic papillary cystadenocarcinoma of the prostate.
AB  - A 62-year-old man was evaluated for lower urinary tract symptoms. Imaging studies
      showed a normal prostate and multiple cysts between the rectum and bladder with
      no evident communication to the prostate. On pathology, papillary
      cystadenocarcinoma with positive immunohistochemical staining for PSA was
      confirmed.

PMID- 17195427
TI  - Topical ocular drug delivery to inner ear disease and sinusitis.
AB  - Oral steroids are the main therapy for sensorineural deafness. We present the
      rare case of a patient whose hearing loss associated with inflammation of the
      inner ear and chronic sinusitis were improved with topical steroid therapy. A 68
      year-old male presented with scleritis in the left eye, inflammation of the inner
      ear and chronic sinusitis. He received oral prednisolone 10 mg/d. However, the
      oral prednisolone was discontinued due to severe side effects. Topical
      administration of 0.1% betamethasone sodium phosphate improved the scleritis and
      incidentally also relieved his symptoms of recurrent otitis and sinusitis after
      several days. Audiometry revealed recovered acoustic sensation in the right ear,
      from 50 dB to 20 dB, and in the left ear from 70 to 35 dB with 1,000 Hz. Topical
      ocular drug delivery of steroids may be effective for inner ear disease and
      sinusitis in patients with systemic side effects to oral steroids.

PMID- 17195428
TI  - A case of metoclopramide-induced oculogyric crisis in a 16-year-old girl with
      cystic fibrosis.
AB  - Oculogyric crisis is a neurologic reaction characterized by bilateral dystonic
      elevation of visual gaze as well as hyperextension of the neck. This reaction is
      most commonly explained as an adverse effect of numerous medications, such as
      dopamine receptor blocking agents or neuroleptic medications and traditional
      antipsychotic or antiemetic drugs, such as prochlorperazine or metoclopramide. A
      case of oculogyric crisis induced by metoclopramide is described in this paper.

PMID- 17195429
TI  - Thalidomide-induced organizing pneumonia.
AB  - Twenty medications are associated with drug-induced organizing pneumonia;
      however, thalidomide is not listed as a potential causative agent. Thalidomide
      (Thalomid, Celgene Corp., Summit, NJ), an angiogenesis inhibitor and
      immunomodulator that reduces tumor necrosis factor-alpha, is used for the
      treatment of multiple myeloma. We report a case of organizing pneumonia in a 58
      year-old male with multiple myeloma treated with dexamethasone and thalidomide.

PMID- 17195431
TI  - Pneumothorax secondary to acupuncture therapy.
AB  - A 27-year-old medical student seeking acupuncture therapy for a right levator
      scapular muscle spasm developed acute dyspnea, chest pain, and nonproductive
      cough within minutes following the treatment. The patient was later diagnosed
      with a 30% pneumothorax of the right lung. Pneumothorax is a well-known adverse
      effect of medical procedures such as central line placement, thoracocentesis and
      transbronchial lung biopsy. This case illustrates another iatrogenic cause of
      pneumothorax--acupuncture-induced pneumothorax. A review of the literature since
      1985 reveals nine case reports of acupuncture-induced pneumothorax.

PMID- 17195430
TI  - Drotrecogin alfa (activated) for nonmenstrual toxic shock syndrome associated
      with methicillin resistant Staphylococcus aureus infection.
AB  - Nonmenstrual toxic shock syndrome (TSS) due to Staphylococcus aureus can lead to
      significant morbidity and mortality. While drotrecogin alfa (DA) has been
      employed in patients with Methicillin-resistant Staphylococcus aureus (MRSA)
      severe sepsis and septic shock, its utility in TSS remains unclear. The authors
      report a case of severe sepsis in the setting of MRSA-associated TSS that
      responded to treatment with DA. This case illustrates a potential role for DA in
      the treatment of toxic shock syndromes and emphasizes the importance of
      aggressive diagnostic and therapeutic modalities in approaching these conditions.

PMID- 17195432
TI  - Postpartum hemoperitoneum due to avulsion of pelvic uterine adhesion band.
AB  - A 31-year-old nulliparous woman presented in labor with preterm rupture of
      membranes at 35 weeks of gestation. The ensuing intrapartum course was
      uneventful, and she delivered a healthy infant (birth weight, 2,850 g) vaginally.
      Four hours after delivery, the patient had a syncopal episode due to hypovolemic
      shock. At laparotomy, a fibrous band between the right fallopian tube and uterus
      was found to be avulsed and actively bleeding, confirming preoperative findings
      obtained with multidetector row computed tomographic angiography.

PMID- 17195433
TI  - Osborn waves in sepsis.
AB  - A patient with severe sepsis, who presented with moderate hypothermia and the
      classical electrocardiographic findings that have been described in patients with
      accidental hypothermia is presented. Rewarming was associated with proportional
      improvement of the initial electrocardiographic abnormalities. A brief discussion
      is included about the electrophysiologic mechanisms of Osborn waves, the
      differential diagnosis of this electrocardiographic finding as well as other
      findings described in patients with hypothermia.

PMID- 17195434
TI  - Postpartum syncope and noncompaction in suspected encephalomyopathy.

PMID- 17195435
TI  - Hearing loss in patient with neurobrucellosis.

PMID- 17195436
TI  - Real-time PCR for quantification of Helicobacter felis in mouse stomach.

PMID- 17195437
TI  - An incidental finding of occult HIV infection.

PMID- 17195438
TI  - Baclofen-induced neurotoxicity in chronic renal failure patients with intractable
      hiccups.

PMID- 17195439
TI  - Coxiella burnetii and lobar pneumonia.

PMID- 17195440
TI  - Atypical presentation of Crohn disease in an Asian-Indian patient.

PMID- 17195441
TI  - Subacute combined degeneration of the spinal cord in a young African-American
      man.

PMID- 17195442
TI  - Redesigning payment of internal medicine: a financial challenge.

PMID- 17195443
TI  - A case of squamous cell lung carcinoma with gastric metastasis.

PMID- 17195444
TI  - Erosive temporomandibular joint involvement: a rare manifestation of
      arthropathies associated with ulcerative colitis.

PMID- 17195445
TI  - Patient's page. Irritable bowel syndrome.

PMID- 17195446
TI  - American plastic surgery in the south since 1906.

PMID- 17195447
TI  - The therapeutic potential of immuno-cell therapy of cancer in combination with
      aminobisphosphonates.
AB  - Many university hospitals and cancer centers in Japan have actively investigated
      the use of autologous activated lymphocyte therapy (ALT). However its therapeutic
      efficacy was found to be quite limited. The efficacy of aminobisphosphonates
      (aBPs) has been shown for osteolytic bone disease. aBPs could activate and induce
      the proliferation of gamma/delta (gamma/delta) T-cells. The application of aBPs
      to ALT in vivo or ex vivo may be beneficial. A brief overview of aBPs and
      gamma/delta T-cells is provided, together with some preliminary results and
      discussion of the therapeutic potential of ALT in combination with aBPs.

PMID- 17195448
TI  - Identification and characterization of lipopolysaccharide in acetic acid
      bacteria.
AB  - BACKGROUND: Lipopolysaccharide (LPS), a major component of the cell walls of Gram
      negative bacteria, was one of the main components of Coley's vaccine and is known
      to have strong adjuvanticity. Though it is known that LPS exists in the digestive
      tract of organisms, the biological significance for the organism has not been
      clarified. In this study, the correlation between the structure and function of
      LPS was determined using acetic acid bacteria. These are Gram-negative bacteria
      consumed in human diets. MATERIALS AND METHODS: Extracts were obtained from a
      strain of acetic acid bacteria which is used for producing vinegar. Determination
      of the LPS neutralizing activity was carried out by the Limulus test. Tumor
      necrosis factor (TNF) and nitric oxide (NO) production were then observed after
      the addition of the extracts to murine monocyte macrophages (RAW264. 7), with or
      without Polymyxin B. TNF production in peritoneal macrophages derived from LPS
      low responsive mice (C3H/HeJ) was studied after the addition of extracts.
      RESULTS: The extracts were shown to be positive only in LPS-specific Limulus test
      and were negative in the (1,3)-beta-D-glucan-specific Limulus test. Both extracts
      induced NO and TNF production in RAW264. 7 cells, but this was inhibited by the
      presence of Polymyxin B. TNF production was inhibited in peritoneal macrophages
      from LPS low-responsive mice (C3H/HeJ). CONCLUSION: LPS with macrophage
      activating activity is present in acetic acid bacteria, routinely consumed by
      humans.

PMID- 17195449
TI  - A soluble 17 kDa tumour necrosis factor (TNF) mutein, TNF-SAM2, with membrane
      bound TNF-like biological characteristics.
AB  - BACKGROUND: Membrane-bound tumour necrosis factor (TNF) has a different binding
      affinity to two TNF receptors (TNFR1 and TNFR2) and shows different biological
      activities compared with TNF-alpha. We have developed a mutein, TNF-SAM2, which
      has modified TNF-alpha. It has higher tumour killing activity than TNF-alpha and
      fewer side effects. MATERIALS AND METHODS: The difference between TNF-SAM2 and
      TNF-alpha was examined in view of the binding affinity to each TNF receptor,
      cytotoxicity and expression of genes using Colo205 cells. RESULTS: The KD value
      of TNF-alpha (2. 9x1-7 M) for TNFR1 was lower than TNF-SAM2 (6.9x10(-7) M).
      Cytotoxicity of TNF-SAM2 was significantly higher than for TNF-a. RNA of Colo205
      cells stimulated with TNF-SAM2 indicated that 80 genes increased by a factor of 2
      or more, and 69 genes decreased. CONCLUSION: TNF-SAM2 can induce different
      intracellular signal transduction in Colo205 cells compared with TNF-alpha. TNF
      SAM2 may have characteristics of the membrane-bound form despite the fact that is
      in a soluble form.

PMID- 17195451
TI  - A case of recurrent ovarian cancer successfully treated with adoptive
      immunotherapy and lentinan.
AB  - BACKGROUND: Immunotherapy is useful for the prevention of the post-operative
      recurrence of some types of cancer and, in combination with certain anticancer
      drugs, is expected to prolong survival time. However, the clinical efficacy of
      immunotherapy alone against advanced cancer has not yet been demonstrated. CASE
      REPORT: A 67-year-old woman with ovarian cancer who had undergone post-operative
      adjuvant chemotherapy suffered from recurrent cancer in the lymph nodes. A
      partial response to adoptive immunotherapy and the administration of the
      biological response modifier, lentinan containing beta-glucan as the principal
      component, was maintained for five months without the use of chemotherapy.
      CONCLUSION: Adoptive immunotherapy with lentinan alone was potentially useful for
      the treatment of lymph node metastases from ovarian cancer.

PMID- 17195450
TI  - Unique molecular characteristics of the environmental responses of mucosal
      macrophages.
AB  - Macrophages are thought to be the cells that initially respond to environmental
      information and transmit this information to other immune cells. We hypothesize
      that there is a "network system" consisting of various tissue macrophages; the
      macrophages respond to stimulation and transmit secondary information to
      neighboring cells, which is important for the maintenance of homeostasis.
      Macrophages exist in all animal organs as tissue macrophages, and their cellular
      characteristics may change as an adaption to tissue-specific environments. It is
      believed that mucosal macrophages are particularly important in the macrophage
      network system because mucosa exist where there is regular exposure to foreign
      substances. However, the molecular mechanism by which intestinal mucosal
      macrophages respond to the external environment is not yet clear. In this review
      the biological characteristics of mucosal macrophages are introduced and how they
      recognize and eradicate various foreign substances is discussed.

PMID- 17195452
TI  - Possible applications of antibodies or their genes in cancer therapy.
AB  - In this review article the possible applications of anti-tumor-associated antigen
      (TAA) antibodies in the therapy of cancer have been summarized. First,
      recombinant monoclonal antibodies (MAbs) are increasingly being used as
      therapeutic agents, especially in combination with anti-cancer drugs. Second,
      conjugation of antibody therapy with toxins or radioisotopes offers more
      therapeutic approaches. Third, development of cytotoxic T-lymphocyte (CTL) or
      natural killer (NK)-cell populations with anti-TAA antibody activity may be
      important for the success of cancer immunotherapy because the downregulated HLA
      class I molecules and the non-ubiquitous expression of NK receptor ligands in
      tumor tissues constitute the major tumor escape mechanism facing tumor-specific
      CTL- and/or NK-cell-mediated responses. Finally, in cancer gene therapy, the
      strategies to target viral vectors carrying therapeutic genes to tumor tissues by
      modifying the tropisms with MAbs or their genes against TAAs are also very
      promising.

PMID- 17195453
TI  - Evaluation of intratumoral administration of tumor necrosis factor-alpha in
      patients with malignant glioma.
AB  - BACKGROUND: This study assessed safety and efficacy for intratumoral
      administration of tumor necrosis factor-a (TNF-SAM2) into the post-operative
      tumor cavity through an Ommaya reservoir for patients with malignant glioma.
      MATERIALS AND METHODS: Seven patients with malignant glioma, comprising 3 cases
      with glioblastoma multiforme (GBM), 3 cases with anaplastic astrocytoma (AA) and
      1 case with malignant ependymoma (ME) were included in the study. All patients
      were pathologically diagnosed and initially treated with adjuvant therapy
      (radiation and/or ranimustine and/or systemic TNF-SAM2 infusion) following
      surgical resection. TNF-SAM2 was administrated into the post-operative tumor
      cavity through a reservoir at a concentration of 1x10(4) U/body when recurrence
      was detected, or as initial induction therapy concomitant with radiotherapy.
      RESULTS: Partial response to this regional immunotherapy was seen in 4 out of 7
      patients, and 1 patient with GBM has remained clinically stable for >184 weeks
      without tumor progression. With AA, 2 cases appeared to display slowed advance
      and longer times to tumor recurrence or regrowth. No serious adverse effects,
      such as brain edema, hemorrhage or seizure were observed, nor systemic
      toxicities. CONCLUSION: Local immunotherapy with TNF-SAM2 may safely contribute
      to therapeutic efficacy in some patients with malignant glioma.

PMID- 17195455
TI  - Anti-tumor activity of de novo designed small globular protein (SGP) in vivo.
AB  - BACKGROUND: The design and synthesis of a small globular protein (SGP) based on
      the colicin family of bacteriocins has previously been reported. It has
      subsequently been shown that this artificial protein possessed cell membrane
      disrupting properties. Here, the anti-tumor effects of SGP in subcutaneous nude
      mice tumor models of human glioma were examined. MATERIALS AND METHODS: Human
      glioblastoma cells (U-87MG) were transplanted subcutaneously into the backs of
      nude mice. When tumor volume was between 100 mm(3) and 350 mm(3), tumors were
      locally injected with SGP three times a week. The four SGP injection groups were
      0.5 mM/50 microl, 0.5 mM/100 microl, 1.0 mM/50 microl and 1.0 mM/100 microl
      (concentration/injection volume). The control group was injected with
      physiological saline; 100 microl three times a week. RESULTS: Tumor volume
      exhibited a statistically significant decrease (p=0.001) and survival was
      significantly longer in the SGP-injected groups (p=0.0001). No clear difference
      in survival time was observed between the 0.5 mM SGP and 1.0 mM SGP groups
      (p=0.0654). However, the reduction in tumor volume was significantly affected by
      SGP concentration (p=0.021). CONCLUSION: SGP has an anti-tumor effect in human
      glioma animal models. The present results also suggest that applied treatment
      based on local injection of SGP will be effective against deep brain-seated
      malignant glioma.

PMID- 17195454
TI  - Mechanisms of small globular protein-induced plasma membrane permeability and
      cytotoxicity in U87-MG human malignant glioblastoma cells.
AB  - BACKGROUND: Small globular protein (SGP) is an artificially designed protein that
      forms small pores on lipid bilayer membranes. The anti-tumor effect of SGP has
      been reported in several papers. However, the exact mechanism underlying SGP
      induced cell death remains to be determined. MATERIALS AND METHODS: The
      mechanisms of SGP-mediated cytotoxicity were examined using cultured malignant
      glioblastoma cells (U87-MG). Morphological changes were observed under a light
      microscope. Ultrastructural changes were examined by electron microscopy. Changes
      in membrane permeability were evaluated by measuring the extracellular release of
      lactate dehydrogenase (LDH) and intracellular calcium concentration ([Ca2+]i). A
      new cell viability assay was also conducted using DAPI/calcein fluorescent-double
      staining methods. RESULTS: SGP cytotoxic effects were strongly influenced by
      fetal bovine serum (FBS) concentration in culture media. After 30 min of
      incubation, cytotoxic effects were noted at SGP concentrations greater than 1.5
      microM. [Ca2+]i increased immediately after SGP addition. Extracellular efflux of
      LDH increased linearly with SGP doses (r(2) =0.936), and occurred even at
      concentrations less than 1.5 microM. Non-viable and viable cells were
      simultaneously detected by fluorescent staining with DAPI and calcein-AM,
      respectively. After 30 min of incubation with SGP, DAPI-positive nuclei were
      evident at concentrations higher than 1.5 microM. Cultures were then maintained
      in 10% FBS-containing media for 24 h before addition of calcein-AM. Calcein
      positive cells were found at SGP concentrations lower than 1.5 5M. Cells positive
      for both DAPI and calcein appeared at a concentration of 1.5 microM. CONCLUSION:
      Our results indicate that SGP induces rapid but transient cytotoxicity, which may
      be beneficial in local therapy of malignant brain tumors.

PMID- 17195456
TI  - Expression of Tn and sialyl-Tn antigens in endometrial cancer: its relationship
      with tumor-produced cyclooxygenase-2, tumor-infiltrated lymphocytes and patient
      prognosis.
AB  - BACKGROUND: Although many tumors arising from epithelial tissues produce mucins,
      little is known regarding the biological significance of mucins in cancer. Recent
      researches have revealed that mucins produced by cancer cells play a critical
      role in the initial induction of cyclooxygenase (COX)-2 in the tumor
      microenvironment. Moreover, the consequence of abnormal glycosylation and
      overexpression of mucins includes suppression of the host-immune function.
      MATERIALS AND METHODS: The expression of Tn/sialyl-Tn (s-Tn) antigen and its
      impact on COX-2 expression by tumor cells and infiltration of CD8+ T-cell into
      the cancer cell nest (nest CD8) in endometrial cancer was evaluated. Tissue
      specimens from 70 endometrial cancer patients who had undergone a curative
      resection were evaluated for Tn/s-Tn antigen, COX-2 and CD8 by
      immunohistochemistry. RESULTS: The overexpression of Tn and s-Tn antigen was
      significantly correlated with COX-2 overexpression (p <0.005 and p <0.001,
      respectively). There was a significant association between s-Tn overexpression
      and low infiltration of nest CD8 (p<0.05). Strong expression of s-Tn antigen was
      significantly associated with poor prognosis (p < 0. 005). Among several
      prognostic factors, s- Tn expression remained the strong independent predictor of
      survival by multivariate analysis (p<0.05). CONCLUSION: These results suggested
      that tumor-produced mucins, which were associated with COX-2 induction and
      immunosuppression, provided additional prognostic information in endometrial
      cancer patients.

PMID- 17195457
TI  - Molecular dynamics of human-specific cytolysin: analysis of membrane binding
      motif for therapeutic application.
AB  - BACKGROUND: Intermedilysin (ILY) is a human-specific cytolysin secreted from
      Streptococcus intermedius. In this study, the dynamic structure of ILY,
      StreptolysinO (SLO) and their 12mer substituted mutants for 500 ps was analyzed.
      Several parameters, such as dipole moment and electrostatic potential, were
      determined to elucidate the molecular mechanism of membrane binding. MATERIALS
      AND METHODS: Molecular models of lLY, SLO and their mutants were constructed
      using Insightll-Discover with the Homology module. Their molecular dynamics were
      simulated with the Discover3 (Insight module), and z-matrix data of the membrane
      binding 12mer region were extracted to calculate the molecular orbital (MO)
      parameters (i.e., dipole moment, solvation free energy (dGW)). RESULTS:
      Cytolysins vibrated like a bow, and the dipole moment direction of ILY 12mer
      region was different from that of SLO. Certain ILY mutants indicated the SLO-like
      dipole properties, which had an SLO-type limer cysteine motif amino acid
      sequence. The ILY 11mer region was more hydrophobic than that of SLO, and seemed
      to interact easily with the cell membrane without cholesterol. The electrostatic
      potential field distribution of ILY differed from that of SLO, especially in the
      11mer region. CONCLUSION: In the 11mer region, the dipole moment directions of
      these cytolysins were constant during molecular movement, and ready to interact
      with membrane components (i.e., cholesterol, phospholipid).

PMID- 17195458
TI  - A bio-defensive function induced by low-dose lipopolysaccharide pre-treatment
      against CCl4-induced fulminant hepatic failure in rats.
AB  - We have investigated the bio-defensive function of low-dose LPS pretreatment on
      CCl4-induced fulminant hepatic failure (FHF) in rats. In male Donryu rats treated
      with CCl4 at 1.0 ml/kg i.p., the serum alanine aminotransferase (ALT) increased
      up to a peak at 24 h. The increase in intracellular Ca2+ concentration was
      biphasic, i.e., a first peak at 1 h and a second at 3 days. However, when rats
      were treated daily with CCl4 at 1.0 ml/kg, serum ALT successively increased over
      several h after the second administration, but the rats died of FHF. The first
      Ca2+ peak occurred 1 h after CCl4 administration, but the concentration did not
      increase continually, until it reached the second peak. However, rats did not die
      when they were treated with lipopolysaccharide at 0.5 mg/kg 24 h prior to the
      initial dose of CCl4 at 1.0 ml/kg. The serum ALT value did not increase after
      administration of CCl4 at 1.0 ml/kg, but the second Ca2+ peak was sustained at >
      1, 000 nM. We concluded that the second Ca2+ peak acts to protect the liver from
      injury.

PMID- 17195459
TI  - A fully human chimeric immune receptor for retargeting T-cells to CEA-expressing
      tumor cells.
AB  - BACKGROUND: Recombinant chimeric immune receptors (CIRs) with anti-CEA
      specificity can retarget grafted T-cells to CEA-expressing tumors in an HLA
      independent manner. To reduce the immunogenicity of conventional CIR in humans,
      an attempt was made to generate a CIR encoded by all human genes. MATERIALS AND
      METHODS: A single-chain variable fragmented (scFv) antibody gene was prepared
      from variable region genes of the C2-45 human mAb clone specific for CEA. The
      scFv gene was connected to a gene construct comprised of the cDNAs for the human
      CD8a hinge region, the human CD28 transmembrane and cytoplasmic domains, and the
      human CD3zeta intracellular domain. The resulting human CIR gene, designated
      L45scFv-CIR, was inserted into the pcDNA3.1 expression vector and transfected
      into human primary T-cells. RESULTS: Flow cytometric analysis using
      allophycocyanin-labeled CEA demonstrated the expression of the L45scFv-CIR
      protein on the T-cells and its specific antigen binding activity. CONCLUSION:
      This L45scFv-CIR gene, consisting of four human genes, may be a useful tool for
      eradication of CEA-expressing but HLA-downregulated tumor cells.

PMID- 17195462
TI  - Perfusion effects and hydrodynamics.
AB  - Biological processes within living systems are significantly influenced by the
      motion of the liquids and gases to which those tissues are exposed. Accordingly,
      tissue engineers must not only understand hydrodynamic phenomena, but also
      appreciate the vital role of those phenomena in cellular and physiologic
      processes both in vitro and in vivo. In particular, understanding the fundamental
      principles of fluid flow underlying perfusion effects in the organ-level internal
      environment and their relation to the cellular microenvironment is essential to
      successfully mimicking tissue behavior. In this work, the major principles of
      hemodynamic flow and transport are summarized, to provide readers with a physical
      understanding of these important issues. In particular, since quantifying
      hemodynamic events through experiments can require expensive and invasive
      techniques, the benefits that can be derived from the use of computational fluid
      dynamics (CFD) packages and neural networking (NN) models are stressed. A
      capstone illustration based on analysis of the hemodynamics of aortic aneurysms
      is presented as a representative example of this approach, to stress the
      importance of tissue responses to flow-induced events.

PMID- 17195461
TI  - Controlling tissue microenvironments: biomimetics, transport phenomena, and
      reacting systems.
AB  - The reconstruction of tissues ex vivo and production of cells capable of
      maintaining a stable performance for extended time periods in sufficient quantity
      for synthetic or therapeutic purposes are primary objectives of tissue
      engineering. The ability to characterize and manipulate the cellular
      microenvironment is critical for successful implementation of such cell-based
      bioengineered systems. As a result, knowledge of fundamental biomimetics,
      transport phenomena, and reaction engineering concepts is essential to system
      design and development. Once the requirements of a specific tissue
      microenvironment are understood, the biomimetic system specifications can be
      identified and a design implemented. Utilization of novel membrane systems that
      are engineered to possess unique transport and reactive features is one
      successful approach presented here. The limited availability of tissue or cells
      for these systems dictates the need for microscale reactors. A capstone
      illustration based on cellular therapy for type 1 diabetes mellitus via
      encapsulation techniques is presented as a representative example of this
      approach, to stress the importance of integrated systems.

PMID- 17195463
TI  - Biopreservation of cells and engineered tissues.
AB  - The development of effective preservation and long-term storage techniques is a
      critical requirement for the successful clinical and commercial application of
      emerging cell-based technologies. Biopreservation is the process of preserving
      the integrity and functionality of cells, tissues and organs held outside the
      native environment for extended storage times. Biopreservation can be categorized
      into four different areas on the basis of the techniques used to achieve
      biological stability and to ensure a viable state following long-term storage.
      These include in vitro culture, hypothermic storage, cryopreservation and
      desiccation. In this chapter, an overview of these four techniques is presented
      with an emphasis on the recent developments that have been made using these
      technologies for the biopreservation of cells and engineered tissues.

PMID- 17195460
TI  - The role of Gc protein oligosaccharide structure as a risk factor for COPD.
AB  - BACKGROUND: The risk of chronic obstructive pulmonary disease (COPD) is related
      to Gc protein allele type, such as Gc*1F, Gc*IS, Gc*2. It has been reported that
      Gc*1F increased COPD risk, while Gc*2 suppressed the risk. Thus, the allele type
      of Gc protein is an important factor in COPD. These Gc proteins differ in sugar
      composition at Thr418 or Thr420. In this study, features of the sugar structure
      of modeled Gc proteins were investigated. MATERIALS AND METHODS: Gc protein
      (GclF, Gc1S, Gc2) models were constructed based on X-ray data of vitamin D
      binding protein (ID=1J7E) using InsightII-Discover with the Homology module, and
      the molecular orbital (MO) parameters [e.g., dipole moment, solvation free energy
      (dGW)] of the oligosaccharide were analyzed. RESULTS: The MO parameter of the
      sugar moiety was different for each Gc protein model. In beta-1,4 bond models,
      the dipole moment of Gc2 protein was larger (56.6 debye) than Gcl type (GclF:
      21.9, Gc1S: 29.8 debye) protein, and it was directed towards the intermolecular
      space. The Gc2 oligosaccharide region was the most hydrophobic (dGW=-999.4 KI)
      among the Gc proteins analyzed in this study. The electrostatic potential (ESP)
      field of beta-1,4 type Gc2 protein was similarly distributed to beta-1,4 linked
      Gcl-type proteins (GclF, GclS). In the beta-1,3 type Gc protein models, the
      results of these parameters (i.e., dipole moment, dGW and ESP) were similar to
      those of beta-1,4 type models. CONCLUSION: The relationship between COPD risk and
      the features of the sugar structure in Gc proteins was examined, and it appeared
      that the active factors (i.e., dipole moment, dGW) might be risk factors for
      COPD, but passive factors (i.e., ESP) did not affect COPD risk. The bond type
      (beta-1,4 or beta-1,3) between galactose and N-acetylgalactosamine did not affect
      the molecular features.

PMID- 17195465
TI  - Engineering skin to study human disease--tissue models for cancer biology and
      wound repair.
AB  - Recent advances in the engineering of three-dimensional tissues known as skin
      equivalents, that have morphologic and phenotypic properties of human skin, have
      provided new ways to study human disease processes. This chapter will supply an
      overview of two such applications--investigations of the incipient development of
      squamous cell cancer, and studies that have characterized the response of human
      epithelium during wound repair. Using these novel tools to study cancer biology,
      it has been shown that cell-cell interactions inherent in three-dimensional
      tissue architecture can suppress early cancer progression by inducing a state of
      intraepithelial dormancy. This dormant state can be overcome and cancer
      progression enabled by altering tissue organization in response to tumor
      promoters or UV irradiation or by modifying the interaction of tumor cells with
      extracellular matrix proteins or their adjacent epithelia. By adapting skin
      equivalent models of human skin to study wound reepithelialization, it has been
      shown that several key responses, including cell proliferation, migration,
      differentiation, growth-factor responsiveness and protease expression, will mimic
      the response seen in human skin. In this light, these engineered models of human
      skin provide powerful new tools for studying disease processes in these tissues
      as they occur in humans.

PMID- 17195464
TI  - Fabrication of three-dimensional tissues.
AB  - The goal of tissue engineering is to restore or replace the lost functions of
      diseased or damaged organs. Ideally, engineered tissues should provide nutrient
      transport, mechanical stability, coordination of multicellular processes, and a
      cellular microenvironment that promotes phenotypic stability. To achieve this
      goal, many engineered tissues require both macro- (approximately cm) and micro-
      (approximately 100 microm) scale architectural features. In recent years,
      techniques from the manufacturing world have been adapted to create scaffolds for
      tissue engineering with defined three-dimensional architectures at
      physiologically relevant length scales. This chapter reviews three-dimensional
      fabrication techniques for tissue engineering, including: acellular scaffolds,
      cellular assembly, and hybrid scaffold/cell constructs.

PMID- 17195466
TI  - Gene-modified tissue-engineered skin: the next generation of skin substitutes.
AB  - Tissue engineering combines the principles of cell biology, engineering and
      materials science to develop three-dimensional tissues to replace or restore
      tissue function. Tissue engineered skin is one of most advanced tissue
      constructs, yet it lacks several important functions including those provided by
      hair follicles, sebaceous glands, sweat glands and dendritic cells. Although the
      complexity of skin may be difficult to recapitulate entirely, new or improved
      functions can be provided by genetic modification of the cells that make up the
      tissues. Gene therapy can also be used in wound healing to promote tissue
      regeneration or prevent healing abnormalities such as formation of scars and
      keloids. Finally, gene-enhanced skin substitutes have great potential as cell
      based devices to deliver therapeutics locally or systemically. Although
      significant progress has been made in the development of gene transfer
      technologies, several challenges have to be met before clinical application of
      genetically modified skin tissue. Engineering challenges include methods for
      improved efficiency and targeted gene delivery; efficient gene transfer to the
      stem cells that constantly regenerate the dynamic epidermal tissue; and
      development of novel biomaterials for controlled gene delivery. In addition,
      advances in regulatable vectors to achieve spatially and temporally controlled
      gene expression by physiological or exogenous signals may facilitate
      pharmacological administration of therapeutics through genetically engineered
      skin. Gene modified skin substitutes are also employed as biological models to
      understand tissue development or disease progression in a realistic three
      dimensional context. In summary, gene therapy has the potential to generate the
      next generation of skin substitutes with enhanced capacity for treatment of
      burns, chronic wounds and even systemic diseases.

PMID- 17195467
TI  - Nanostructured biomaterials for tissue engineering bone.
AB  - Advances in several critical research fields (processing, catalytic, optical,
      actuation, electrical, mechanical, etc.) have started to benefit from
      nanotechnology. Nano-technology can be broadly defined as the use of materials
      and systems whose structures and components exhibit novel and significantly
      changed properties when control is gained at the atomic, molecular, and
      supramolecular levels. Specifically, such advances have been found for materials
      when particulate size is decreased to below 100 nm. However, to date, relatively
      few advantages have been described for biological applications (specifically,
      those involving bone tissue engineering). This chapter elucidates several
      promising examples of how nanophase materials can be used to improve orthopedic
      implant applications. These include mechanical advantages as well as altered cell
      functions, leading to increased bone tissue regeneration on a wide range of
      nanophase materials including ceramics, polymers, metals, and composites thereof.
      Such advances were previously unimaginable with conventional materials possessing
      large micron-sized particulates.

PMID- 17195468
TI  - Integration of technologies for hepatic tissue engineering.
AB  - The liver is the largest internal organ in the body, responsible for over 500
      metabolic, regulatory, and immune functions. Loss of liver function leads to
      liver failure which causes over 25,000 deaths/year in the United States. Efforts
      in the field of hepatic tissue engineering include the design of bioartificial
      liver systems to prolong patient's lives during liver failure, for drug toxicity
      screening and for the study of liver regeneration, ischemia/reperfusion injury,
      fibrosis, viral infection, and inflammation. This chapter will overview the
      current state-of-the-art in hepatology including isolated perfused liver, culture
      of liver slices and tissue explants, hepatocyte culture on collagen "sandwich"
      and spheroids, coculture of hepatocytes with non-parenchymal cells, and the
      integration of these culture techniques with microfluidics and reactor design.
      This work will discuss the role of oxygen and medium composition in hepatocyte
      culture and present promising new technologies for hepatocyte proliferation and
      function. We will also discuss liver development, architecture, and function as
      they relate to these culture techniques. Finally, we will review current
      opportunities and major challenges in integrating cell culture, bioreactor
      design, and microtechnology to develop new systems for novel applications.

PMID- 17195470
TI  - Applications of transcriptional profiling in antibiotics discovery and
      development.
AB  - This chapter will review specific applications of microarray technology and
      related data analysis strategies in antibacterial research and development. We
      present examples of microarray applications spanning the entire antibiotics
      research and development pipeline, from target discovery, assay development,
      pharmacological evaluation, to compound safety studies. This review emphasizes
      the utility of microarrays for a systematic evaluation of novel chemistry as
      antibiotic agents. Transcriptional profiling has revolutionized the process of
      target elucidation and has the potential to offer substantial guidance in the
      identification of new targets. Microarrays will continue to be a workhorse of
      anti-infectives discovery programs ranging from efficacy assessments of
      antibiotics ('forward pharmacology') to drug safety evaluations
      ('toxicogenomics').

PMID- 17195469
TI  - Systems biology and its impact on anti-infective drug development.
AB  - Systems biology offers the potential for more effective selection of novel
      targets for anti-infective drugs. In contrast to conventional reductionist
      biology, a systems approach allows targets to be viewed in a wider context of the
      entire physiology of the cell, with the potential to identify key susceptible
      nodes and to predict synergistic effects of blocking multiple pathways. In
      addition to the holistic perspective provided by systems biology, the emphasis on
      quantitative analysis is likely to add further rigour to the process of target
      selection. Systems biology also offers the potential to incorporate different
      levels of information into the selection process. Consideration of data from
      microbial population biology may be important in the context of predicting future
      drug-resistance profiles associated with targeting a particular pathway, for
      example. This chapter provides an overview of major themes in the developing
      field of systems biology, summarising the core technologies and the strategies
      used to translate datasets into useful quantitative models capable of predicting
      complex biological behaviour.

PMID- 17195471
TI  - Chemical genetics: an evolving toolbox for target identification and lead
      optimization.
AB  - Chemical genetics combines chemistry with biology as a means of exploring the
      function of unknown proteins or identifying the proteins responsible for a
      particular phenotype. Chemical genetics is thus a valuable tool in the
      identification of novel drug targets. This chapter describes the application of
      chemical genetics in traditional and systems-based approaches to drug target
      discovery and the tools/approaches that appear most promising for guiding future
      pharmaceutical development.

PMID- 17195472
TI  - Proteomic profiling of cellular stresses in Bacillus subtilis reveals cellular
      networks and assists in elucidating antibiotic mechanisms of action.
AB  - Proteomic profiling provides a global view of the protein composition of the
      cell. In contrast to the static nature of the genome sequence, which provides the
      blueprint for all protein-based cellular building blocks, the proteome is highly
      dynamic. The protein composition is constantly adjusting to facilitate survival,
      growth, and reproduction in an ever-changing environment. In a quest to
      understand the regulation of cellular networks in bacteria and the role of
      individual proteins in the adaptation process, the proteomic response to stress
      and starvation was analyzed in wild-type and mutant strains. The knowledge
      derived from these proteomic studies was applied to investigating the bacterial
      response to antibiotics. It was found that proteomics presents a powerful tool
      for hypothesis generation regarding antibiotic mechanism of action.

PMID- 17195473
TI  - Elucidating the mode-of-action of compounds from metabolite profiling studies.
AB  - Metabolite profiling has been carried out for decades and is as such not a new
      research area. However, the field has attracted increasing attention in the last
      couple of years, and the term metabolome is now often used to describe the
      complete pool of metabolites associated with an organism at any given time. Mass
      spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the best
      candidates for comprehensive analysis of the metabolome and the application of
      these technologies is presented in this chapter. In this relation, the importance
      of efficient metabolite screening for discovery of novel drugs is discussed.
      Related to metabolite profiling, the principals underlying the application of
      labeled substrates to quantify in vivo metabolic fluxes are introduced, and the
      chapter is concluded by discussing the perspectives of metabolite measurements in
      systems biology.

PMID- 17195474
TI  - A subsystems-based approach to the identification of drug targets in bacterial
      pathogens.
AB  - This chapter describes a three-stage approach to target identification based upon
      subsystem analysis. Subsystems analysis focuses on related metabolic pathways as
      a unit and is a biochemically-informed approach to target selection. The process
      involves three stages of analysis; the first stage, selection of the target
      subsystem, is guided by information about its essentiality and on the predicted
      vulnerability of the targeted pathway or enzyme to inhibition. The second stage
      involves analysis of the target subsystem by means of comparative genomics,
      including genome context analysis and metabolic reconstruction. The third stage
      evaluates the selection of the specific target genes within the subsystem by
      target prioritization and validation. The whole process allows for a careful
      consideration of spectrum, drugability, biological rationale and the metabolic
      role of the specific target within the context of an integrated circuit within a
      specific metabolic pathway.

PMID- 17195476
TI  - The protein network as a tool for finding novel drug targets.
AB  - Proteins are often referred to as the molecular workhorses of the cell since they
      are responsible for the majority of functions within a living cell. From the
      generation of energy, to the replication of DNA, proteins play a central role in
      most cellular functions. Because of their importance to cellular viability,
      proteins are commonly the target of therapeutic drugs, ranging from antimicrobial
      to anticancer drugs. With the rise of drug resistant and multi-drug resistant
      forms of many diseases, it has become increasingly important to develop new
      strategies to identify alternative drug targets. One such strategy arises from
      the analysis of protein networks. Protein networks help define individual
      proteins within the context of all other cellular proteins. In this chapter we
      discuss methods for the identification and analysis of genome-wide protein
      networks, and discuss how protein networks can be used to aid the identification
      of novel drug targets.

PMID- 17195475
TI  - Metabolic control analysis to identify optimal drug targets.
AB  - This chapter describes the basic principles of Metabolic Control Analysis (MCA)
      which is a quantitative methodology to evaluate the importance and relative
      contribution of individual metabolic steps in the overall functioning of a
      particular system. The control on the flux through a metabolic pathway or
      subsystem can be quantified by the control coefficients of the individual enzymes
      or components which reflects the extent to which the component is rate-limiting.
      The perturbation of an individual step is measured by its elasticity coefficient.
      The effect of perturbation of a single step on the entire pathway or subsystem
      is, in turn, measured by the response coefficient. Differential control analysis
      can be used to compare flux through a single metabolic pathway in a pathogen with
      the same pathway in its host to identify uniquely vulnerable steps with the
      greatest potential for specifically inhibiting flux through the pathogen
      metabolic pathway. The utility of this methodology is illustrated with the
      glycolysis in Trypanosomes and with oncogenic signaling.

PMID- 17195477
TI  - Toxicogenomics applied to predictive and exploratory toxicology for the safety
      assessment of new chemical entities: a long road with deep potholes.
AB  - Toxicology is the perturbation of metabolism by external factors such as
      xenobiotics, environmental factors or drugs. As such, toxicology covers a broad
      range of fields from studies of the whole organism responses to minute
      biochemical events. Mechanistic toxicogenomics is an attempt to harness genomic
      tools to understand the physiological basis for a toxic event based on an
      analysis of transcriptional, translational or metabolomic profiles. These studies
      are complicated by non-toxic adaptive responses in transcript, protein or
      metabolite expression levels that have to be distinguished from those that are
      proximally related to the toxic event. Substantial progress has been made on the
      identification of biomarkers and the establishment of screens derived from such
      toxicogenomics studies. The ultimate goal, of course, is predictive
      toxicogenomics, which is an attempt to infer the likelihood of occurrence of a
      toxic event with exposure to a new agent based upon comparative responses with
      large databases of gene, protein or metabolite expression data. Gene expression
      databases are currently limited by the fact that measurable toxic phenotypes
      generally precede or at best coincide with the earliest observable changes in
      transcriptional profiles. Unfortunately, predictive protein databases have been
      limited by technical difficulties. Metabonomics-based databases, which would
      probably have the highest predictive value, are limited in turn by the inability
      to perform high dose studies in humans. This chapter will conclude by reviewing
      those elements of toxicogenomics that apply specifically to the development of
      anti-infectives and the potential for accurately modelling the toxicity of future
      drugs.

PMID- 17195478
TI  - Biological robustness in complex host-pathogen systems.
AB  - Infectious diseases are still the number one killer of human beings. Even in
      developed countries, infectious diseases continue to be a major health threat.
      This article explores a conceptual framework for understanding infectious
      diseases in the context of the complex dynamics between microbe and host, and
      explores theoretical strategies for anti-infectives. The central pillar of this
      conceptual framework is that biological robustness is a fundamental property of
      systems that is closely interlinked with the evolution of symbiotic host-pathogen
      systems. There are specific architectural features of such robust yet evolvable
      systems and interpretable trade-offs between robustness, fragility, resource
      demands, and performance. This concept applies equally to both microbes and host.
      Pathogens have evolved to exploit the host using various strategies as well as
      effective escape mechanisms. Modular pathogenicity islands (PAI) derived from
      horizontal gene transfer, highly variable surface molecules, and a range of other
      countermeasures enhance the robustness of a pathogen against attacks from the
      host immune system. The host has likewise evolved complex defensive mechanisms to
      protect itself against pathogenic threats, but the host immune system includes
      several trade-offs that can be exploited by pathogens and induces undesirable
      inflammatory reactions. Due to the complexity of the dynamics emerging from the
      interactions of multiple microbes and a host, effective counter-measures require
      an in-depth understanding of system dynamics as well as detailed molecular
      mechanisms of the processes that are involved.

PMID- 17195479
TI  - Toward whole cell modeling and simulation: comprehensive functional genomics
      through the constraint-based approach.
AB  - The increasing availability of various system-level, or so-called 'omics',
      datasets, in concert with existing data from the primary research literature, is
      facilitating the development of genome-scale metabolic models for many organisms.
      By incorporating the metabolic reaction stoichiometry as well as other
      physicochemical properties into systemic network reconstructions, these models
      account for the constraints that restrict an organism's phenotypic behavior.
      Accordingly, unlike many contemporary modeling strategies, this constraint-based
      modeling approach does not attempt to predict network behavior exactly; rather,
      it seeks to clearly distinguish those network states that a system can achieve
      from those that it cannot. A variety of analytical tools have been designed and
      developed to probe these models, thus enabling studies that investigate the
      metabolic capabilities of a number of organisms, that generate and test
      experimental hypotheses, and that predict accurately metabolic phenotypes and
      evolutionary outcomes. This chapter introduces the concepts that underlie the
      constraint-based modeling approach, and describes several of its applications
      with an emphasis on those potentially relevant to the drug development field. In
      addition, while this chapter focuses on the primary application of the constraint
      based approach to date, namely in modeling metabolic networks, the latter
      sections of the chapter discuss its relatively recent application to modeling
      other cellular systems. Finally, the chapter concludes with an assessment of
      future directions focusing on the efforts that will be required to utilize the
      constraint-based approach in generating a holistic model of a viable organism.

PMID- 17195480
TI  - Genomics of host-pathogen interactions.
AB  - The complete sequences of hundreds of microbial genomes have provided drug
      discovery pipelines with thousands of new potential drug targets. Their
      availability has also stimulated the development of a variety of innovative
      approaches that allow functional studies to be performed on the entire genome of
      an organism. This chapter describes how these approaches have been applied to the
      analysis of host-pathogen interactions and discusses how such studies might
      facilitate the development of new antibiotics.

PMID- 17195481
TI  - [Hazardous chemical discharge behavior of chemical waste sites exemplified by the
      old "Antonie Pit" dump in Bitterfeld. Studies and evaluation of results including
      determination of a method for ascertaining and evaluating hazardous chemical
      discharge behavior].

PMID- 17195482
TI  - Feasibility study of using brine for carbon dioxide capture and storage from
      fixed sources.
AB  - A laboratory-scale reactor was developed to evaluate the capture of carbon
      dioxide (CO2) from a gas into a liquid as an approach to control greenhouse gases
      emitted from fixed sources. CO2 at 5-50% concentrations was passed through a gas
      exchange membrane and transferred into liquid media--tap water or simulated
      brine. When using water, capture efficiencies exceeded 50% and could be enhanced
      by adding base (e.g., sodium hydroxide) or the combination of base and carbonic
      anhydrase, a catalyst that speeds the conversion of CO2 to carbonic acid. The
      transferred CO2 formed ions, such as bicarbonate or carbonate, depending on the
      amount of base present. Adding precipitating cations, like Ca++, produced
      insoluble carbonate salts. Simulated brine proved nearly as efficient as water in
      absorbing CO2, with less than a 6% reduction in CO2 transferred. The CO2 either
      dissolved into the brine or formed a mixture of gas and ions. If the chemistry
      was favorable, carbonate precipitate spontaneously formed. Energy expenditure of
      pumping brine up and down from subterranean depths was modeled. We conclude that
      using brine in a gas-exchange membrane system for capturing CO2 from a gas stream
      to liquid is technically feasible and can be accomplished at a reasonable
      expenditure of energy.

PMID- 17195483
TI  - Quality-assured measurements of animal building emissions: particulate matter
      concentrations.
AB  - Federally funded, multistate field studies were initiated in 2002 to measure
      emissions of particulate matter (PM) < 10 microm (PM10) and total suspended
      particulate (TSP), ammonia, hydrogen sulfide, carbon dioxide, methane, nonmethane
      hydrocarbons, and odor from swine and poultry production buildings in the United
      States. This paper describes the use of a continuous PM analyzer based on the
      tapered element oscillating microbalance (TEOM). In these studies, the TEOM was
      used to measure PM emissions at identical locations in paired barns. Measuring PM
      concentrations in swine and poultry barns, compared with measuring PM in ambient
      air, required more frequent maintenance of the TEOM. External screens were used
      to prevent rapid plugging of the insect screen in the PM10 preseparator inlet.
      Minute means of mass concentrations exhibited a sinusoidal pattern that followed
      the variation of relative humidity, indicating that mass concentration
      measurements were affected by water vapor condensation onto and evaporation of
      moisture from the TEOM filter. Filter loading increased the humidity effect, most
      likely because of increased water vapor adsorption capacity of added PM. In a
      single layer barn study, collocated TEOMs, equipped with TSP and PM10 inlets,
      corresponded well when placed near the inlets of exhaust fans in a layer barn.
      Initial data showed that average daily mean concentrations of TSP, PM10, and
      PM2.5 concentrations at a layer barn were 1440 +/- 182 microg/m3 (n = 2), 553 +/-
      79 microg/m3 (n = 4), and 33 +/- 75 microg/m3 (n = 1), respectively. The daily
      mean TSP concentration (n = 1) of a swine barn sprinkled with soybean oil was 67%
      lower than an untreated swine barn, which had a daily mean TSP concentration of
      1143 +/- 619 microg/m3. The daily mean ambient TSP concentration (n = 1) near the
      swine barns was 25 +/- 8 microg/m3. Concentrations of PM inside the swine barns
      were correlated to pig activity.

PMID- 17195484
TI  - Uncertainty analysis of integrated gasification combined cycle systems based on
      Frame 7H versus 7F gas turbines.
AB  - Integrated gasification combined cycle (IGCC) technology is a promising
      alternative for clean generation of power and coproduction of chemicals from coal
      and other feedstocks. Advanced concepts for IGCC systems that incorporate state
      of-the-art gas turbine systems, however, are not commercially demonstrated.
      Therefore, there is uncertainty regarding the future commercial-scale
      performance, emissions, and cost of such technologies. The Frame 7F gas turbine
      represents current state-of-practice, whereas the Frame 7H is the most recently
      introduced advanced commercial gas turbine. The objective of this study was to
      evaluate the risks and potential payoffs of IGCC technology based on different
      gas turbine combined cycle designs. Models of entrained-flow gasifier-based IGCC
      systems with Frame 7F (IGCC-7F) and 7H gas turbine combined cycles (IGCC-7H) were
      developed in ASPEN Plus. An uncertainty analysis was conducted. Gasifier carbon
      conversion and project cost uncertainty are identified as the most important
      uncertain inputs with respect to system performance and cost. The uncertainties
      in the difference of the efficiencies and costs for the two systems are
      characterized. Despite uncertainty, the IGCC-7H system is robustly preferred to
      the IGCC-7F system. Advances in gas turbine design will improve the performance,
      emissions, and cost of IGCC systems. The implications of this study for decision
      making regarding technology selection, research planning, and plant operation are
      discussed.

PMID- 17195485
TI  - Continuous monitoring of particle emissions during showering.
AB  - Particle formation from showering may be attributed to dissolved mineral aerosols
      remaining after evaporation of micron-sized satellite droplets produced by the
      showerhead or from splashing of larger shower water droplets on surfaces.
      Duplicate continuous particle monitors measured particle size distributions in a
      ventilated residential bathroom under various showering conditions, using a full
      size mannequin in the shower to simulate splashing effects during showering.
      Particle mass concentrations were estimated from measured shower particle number
      densities and used to develop emission factors for inhalable particles. Emission
      source strengths of 2.7-41.3 microg/ m3/min were estimated under the various test
      conditions using residential tap water in Columbus, OH. Calculated fine
      particulate matter (PM2.5) concentrations in the bathroom reached several hundred
      micrograms per cubic meter; calculated coarse particulate matter (PM10) levels
      approached 1000 microg/m3. Rates of particle formation tended to be highest for
      coarse shower spray settings with direct impact on the mannequin. No consistent
      effects of water temperature, water pressure, or spray setting on overall
      emission rates were apparent, although water temperature and spray setting did
      have an effect when varied within a single shower sampling run. Salt solutions
      were injected into the source water during some tests to assess the effects of
      total dissolved solids on particle emission rates. Injection of salts was shown
      to increase the PM2.5 particle formation rate by approximately one third, on
      average, for a doubling in tap water-dissolved solids content; PM10 source
      strengths approximately doubled under these conditions, because very few
      particles >10 microm were formed.

PMID- 17195486
TI  - Is levoglucosan a suitable quantitative tracer for wood burning? Comparison with
      receptor modeling on trace elements in Lycksele, Sweden.
AB  - Particle emissions from residential wood combustion in small communities in
      Northern Sweden can sometimes increase the ambient particle concentrations to
      levels comparable to densely trafficked streets in the center of large cities.
      The reason for this is the combination of increased need for domestic heating
      during periods of low temperatures, leading to higher emission rates, and stable
      meteorological conditions. In this work, the authors compare two different
      approaches to quantify the wood combustion contribution to fine particles in
      Northern Sweden: a multivariate source-receptor analysis on inorganic compounds
      followed by multiple linear regression (MLR) of fine particle concentrations and
      levoglucosan used as a tracer. From the receptor model, it can be seen that
      residential wood combustion corresponds with 70% of modeled particle mass.
      Smaller contributions are also seen from local nonexhaust traffic particles, road
      dust, and brake wear (each contributing 14%). Of the mass, 1.5% is explained by
      long-distance transported particles, and 2% derives from a regional source
      deriving from either oil combustion or smelter activities. In samples collected
      in ambient air, a significant linear correlation was found between wood burning
      particles and levoglucosan. The levoglucosan fraction in the ambient fine
      particulate matter attributed to wood burning according to the multivariate
      analysis ranged from < 2% to 50%. This is much higher than the fraction found in
      the emission from the boilers expected to be responsible for most emissions at
      this site (between 3% and 6%). A laboratory emission study of wood and pellet
      boilers gave 0.3% wt to 22% wt levoglucosan to particle mass, indicating that the
      levoglucosan fraction may be highly dependent on combustion conditions, making it
      uncertain to use it as a quantitative tracer under real-world burning conditions.
      Thus, quantitative estimates of wood burning contributions will be very uncertain
      using solely levoglucosan as a tracer.

PMID- 17195487
TI  - Processes influencing secondary aerosol formation in the San Joaquin Valley
      during winter.
AB  - Air quality data collected in the California Regional PM10/ PM(2.5) Air Quality
      Study (CRPAQS) are analyzed to qualitatively assess the processes affecting
      secondary aerosol formation in the San Joaquin Valley (SJV). This region
      experiences some of the highest fine particulate matter (PM(2.5)) mass
      concentrations in California (< or = 188 microg/m3 24-hr average), and secondary
      aerosol components (as a group) frequently constitute over half of the fine
      aerosol mass in winter. The analyses are based on 15 days of high-frequency
      filter and canister measurements and several months of wintertime continuous gas
      and aerosol measurements. The phase-partitioning of nitrogen oxide (NO(x))
      related nitrogen species and carbonaceous species shows that concentrations of
      gaseous precursor species are far more abundant than measured secondary aerosol
      nitrate or estimated secondary organic aerosols. Comparisons of ammonia and
      nitric acid concentrations indicate that ammonium nitrate formation is limited by
      the availability of nitric acid rather than ammonia. Time-resolved aerosol
      nitrate data collected at the surface and on a 90-m tower suggest that both the
      daytime and nighttime nitric acid formation pathways are active, and entrainment
      of aerosol nitrate formed aloft at night may explain the spatial homogeneity of
      nitrate in the SJV. NO(x) and volatile organic compound (VOC) emissions plus
      background O3 levels are expected to determine NO(x) oxidation and nitric acid
      production rates, which currently control the ammonium nitrate levels in the SJV.
      Secondary organic aerosol formation is significant in winter, especially in the
      Fresno urban area. Formation of secondary organic aerosol is more likely limited
      by the rate of VOC oxidation than the availability of VOC precursors in winter.

PMID- 17195488
TI  - Fine particulate chemical composition and light extinction at Meadview, AZ.
AB  - The concentration of fine particulate nitrate, sulfate, and carbonaceous material
      was measured for 12-hr day-night samples using diffusion denuder samplers during
      the Project Measurement of Haze and Visibility Effects (MOHAVE) July to August
      1992 Summer Intensive study at Meadview, AZ, just west of Grand Canyon National
      Park. Organic material was measured by several techniques. Only the diffusion
      denuder method measured the semivolatile organic material. Fine particulate
      sulfate and nitrate (using denuder technology) determined by various groups
      agreed. Based on the various collocated measurements obtained during the Project
      MOHAVE study, the precision of the major fine particulate species was +/- 0.6
      microg/m3 organic material, +/- 0.3 microg/m3 ammonium sulfate, and +/- 0.07
      microg/m3 ammonium nitrate. Data were also available on fine particulate crustal
      material, fine and coarse particulate mass from the Interagency Monitoring of
      Protected Visual Environments sampling system, and relative humidity (RH), light
      absorption, particle scattering, and light extinction measurements from Project
      MOHAVE. An extinction budget was obtained using mass scattering coefficients
      estimated from particle size distribution data. Literature data were used to
      estimate the change in the mass scattering coefficients for the measured species
      as a function of RH and for the absorption of light by elemental carbon. Fine
      particulate organic material was the principal particulate contributor to light
      extinction during the study period, with fine particulate sulfate as the second
      most important contributor. During periods of highest light extinction,
      contributions from fine particulate organic material, sulfate, and light
      absorbing carbon dominated the extinction of light by particles. Particle light
      extinction was dominated by sulfate and organic material during periods of lowest
      light extinction. Combination of the extinction data and chemical mass balance
      analysis of sulfur oxides sources in the region indicate that the major
      anthropogenic contributors to light extinction were from the Los Angeles, CA, and
      Las Vegas, NV, urban areas. Mohave Power Project associated secondary sulfate was
      a negligible contributor to light extinction.

PMID- 17195489
TI  - Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans from various
      industrial sources.
AB  - This study characterized the emissions of polychlorinated dibenzo-p-dioxins
      (PCDDs) and polychlorinated dibenzofurans (PCDFs) from the stack flue gases of 17
      industrial sources, which were classified into 10 categories. The results show
      that the mean PCDD/PCDF concentration of secondary zinc smelter (Zn-S) and
      secondary copper smelter (Cu-S) is 2.44 ng international toxic equivalent (I
      TEQ)/Nm3 (N represents normal conditions at 0 degrees C, 760 mmHg), which was
      found to be significantly greater than that of industrial waste incinerators
      (mean concentration = 0.15 ng I-TEQ/Nm3). These results imply that the
      controlling of secondary metallurgical melting processes is more important than
      industrial waste incineration for the reduction of PCDD/PCDF emissions. The mean
      emission factors of cement production, Zn-S and Cu-S, are 0.052, 1.99, and 1.73
      microg I-TEQ/t product, respectively. For industrial waste incineration, the mean
      emission factors of waste rubber, waste liquor, waste sludge, industrial waste
      solid (IWI)-1, IWI-2, IWI-3, and IWI-4 are 0.752, 0.435, 0.760, 6.64, 1.67, 2.38,
      and 0.094 microg I-TEQ/t feed, respectively. Most of the PCDD/PCDF emission
      factors established in this study are less than those reported in previous
      studies, which could be because of the more stringent regulations for PCDD/PCDF
      emissions in recent years.

PMID- 17195490
TI  - Spatial and temporal variability of ambient air toxics data.
AB  - This paper summarizes information on the spatial and temporal variability of
      selected air toxics pollutants collected on a national basis primarily for a
      period encompassing 1990-2003. Spatial information on pollutant concentrations is
      characterized in terms of within-city and between-city variability. Temporal
      information is summarized as diurnal and seasonal variability and in multiyear
      trends. The information on variability is presented in the framework of a larger
      need for systematic documentation of information on air toxics pollutants to
      assess progress in air pollution control programs.

PMID- 17195491
TI  - Correlation between calcium carbonate content and emission characteristics of
      incense.
AB  - In Taiwan and China, calcium carbonate is commonly added as a filler during
      incense production to lower the cost. This study has found an unexpected benefit
      for this practice: it reduces particulate emission. Nine types of the popular
      incense on the local market were chosen for this study. The calcium content in
      raw material incense was analyzed by inductively coupled plasma atomic emission
      spectrometry, followed by X-ray diffraction (XRD) spectroscopy. The correlation
      between the calcium content and emission characteristics of incense was
      investigated. The calcium content varied from 1.8 to 60 mg/g (incense burned)
      among those nine different types of incense. Very little calcium (< 1%) was found
      in natural wood or plants, which is mainly the raw material of incense. Instead,
      most calcium was artificially added in the form of CaCO3 during manufacturing.
      The combustion characteristics, including burning rate, emission factors of
      particulate, ash, and solid-phase polycyclic aromatic hydrocarbons (S-PAHs),
      varied significantly among the nine types of incense. Incense containing 2%
      calcium would emit 30% less S-PAHs, compared with those with little (< 0.2%)
      calcium. More importantly, increasing the calcium content from 0.5 to 5% by
      adding CaCO3 reduced the particulate emission from incense by approximately 50%.

PMID- 17195492
TI  - Validation of three new methods for determination of metal emissions using a
      modified Environmental Protection Agency Method 301.
AB  - Three new methods applicable to the determination of hazardous metal
      concentrations in stationary source emissions were developed and evaluated for
      use in U.S. Environmental Protection Agency (EPA) compliance applications. Two of
      the three independent methods, a continuous emissions monitor-based method (Xact)
      and an X-ray-based filter method (XFM), are used to measure metal emissions. The
      third method involves a quantitative aerosol generator (QAG), which produces a
      reference aerosol used to evaluate the measurement methods. A modification of EPA
      Method 301 was used to validate the three methods for As, Cd, Cr, Pb, and Hg,
      representing three hazardous waste combustor Maximum Achievable Control
      Technology (MACT) metal categories (low volatile, semivolatile, and volatile).
      The modified procedure tested the methods using more stringent criteria than EPA
      Method 301; these criteria included accuracy, precision, and linearity. The
      aerosol generation method was evaluated in the laboratory by comparing actual
      with theoretical aerosol concentrations. The measurement methods were evaluated
      at a hazardous waste combustor (HWC) by comparing measured with reference aerosol
      concentrations. The QAG, Xact, and XFM met the modified Method 301 validation
      criteria. All three of the methods demonstrated precisions and accuracies on the
      order of 5%. In addition, correlation coefficients for each method were on the
      order of 0.99, confirming the methods' linear response and high precision over a
      wide range of concentrations. The measurement methods should be applicable to
      emissions from a wide range of sources, and the reference aerosol generator
      should be applicable to additional analytes. EPA recently approved an alternative
      monitoring petition for an HWC at Eli Lilly's Tippecanoe site in Lafayette, IN,
      in which the Xact is used for demonstrating compliance with the HWC MACT metal
      emissions (low volatile, semivolatile, and volatile). The QAG reference aerosol
      generator was approved as a method for providing a quantitative reference
      aerosol, which is required for certification and continuing quality assurance of
      the Xact.

PMID- 17195493
TI  - Effects of the basicity on the comelting conditions of municipal solid waste
      incinerator fly ash and sewage sludge ash.
AB  - In this study, the effects of the basicity on the pouring point of the municipal
      solid waste incinerator fly ash-sewage sludge ash mixture is investigated. Four
      kinds of sewage sludge ash, which were collected from several primary and
      secondary sewage treatment plants and were produced by different processes and
      sludge conditioning alternatives, were used as modifiers. The results indicate
      that the pouring point of the mixture increased with increasing basicity, within
      the range of 0.65-1.90. The pouring point is affected by the contents of the
      mixtures (CaO, SiO2, Al2O3, and the flux). It is suggested that an increase in
      the CaO content tends to raise the pouring point, whereas an increase in the SiO2
      and/or the Al2O3 contents cause as adverse reaction. The prediction equation,
      obtained by multilinear regression (significant level is 0.05), is as follows:
      pouring temperature = 1189.6 + 4.19 CaO - 0.96 SiO2 - 4.33 Al2O3 (R2 = 0.91). In
      general, the pouring point decreased when the basicity was < 1. The pouring point
      apparently increased when the basicity was > 1.2. The regression squares for the
      different basicities were between 0.84 and 0.91. From these relationships, we
      note that a basicity index of 5 gave the best R2 (0.91). From the results of this
      study, it can be concluded that the modification of the basicity of the fly ash
      by the addition of sewage sludge ash to lower the pouring point is feasible and
      leads to a more energy-efficient melting process. In addition, these synthetic
      slags have a good pozzolanic reactive activity.

PMID- 17195495
TI  - Suicide: ending motherhood.

PMID- 17195494
TI  - The Steubenville Comprehensive Air Monitoring Program (SCAMP): concentrations and
      solubilities of PM(2.5) trace elements and their implications for source
      apportionment and health research.
AB  - The elemental compositions of the water-soluble and acid-digestible fractions of
      24-hr integrated fine particulate matter (PM(2.5)) samples collected in
      Steubenville, OH, from 2000 to 2002 were determined using dynamic reaction cell
      inductively coupled plasma-mass spectrometry. The water-soluble elemental
      compositions of PM(2.5) samples collected at four satellite monitoring sites in
      the surrounding region were also determined. Fe was the most abundant but least
      water soluble of the elements determined at the Steubenville site, having a mean
      ambient concentration of 272 ng/m3 and a median fractional solubility of 6%. Fe
      solubility and its correlations with SO4(2-) and temperature varied significantly
      by season, consistent with the hypothesis that secondary sulfates may help to
      mobilize soluble Fe under suitable summertime photochemical conditions.
      Significantly higher ambient concentrations were observed at Steubenville than at
      each of the four satellite sites for 10 of the 18 elements (Al, As, Ca, Cd, Fe,
      Mg, Mn, Na, Pb, and Zn) determined in the water-soluble PM(2.5) fraction.
      Concentrations of Fe, Mn, and Zn at Steubenville were substantially higher than
      concentrations reported recently for larger U.S. cities. Receptor modeling
      identified seven sources affecting the Steubenville site. An (NH4)2SO4-dominated
      source, likely representing secondary PM(2.5) from coal-fired plants to the west
      and southwest of Steubenville, accounted for 42% of the PM(2.5) mass, and two
      sources likely dominated by emissions from motor vehicles and from iron and steel
      facilities in the immediate Steubenville vicinity accounted for 20% and 10%,
      respectively. Other sources included an NH4NO3 source (15%), a crustal source
      (6%), a mixed nonferrous metals and industrial source (3%), and a primary coal
      combustion source (3%). Results suggest the importance of very different regional
      and local source mechanisms in contributing to PM(2.5) mass at Steubenville and
      reinforce the need for further research to elucidate whether metals such as Fe,
      Mn, and Zn play a role in the PM(2.5) health effects observed previously there.

PMID- 17195496
TI  - Placards at the house.

PMID- 17195497
TI  - Time to rest.

PMID- 17195498
TI  - Campaign for Normal Birth. Jane's story.

PMID- 17195499
TI  - Representing the members.

PMID- 17195500
TI  - Examining skills and practice.

PMID- 17195501
TI  - Turning the breech using moxibustion.

PMID- 17195502
TI  - Confidentiality and standards of care.

PMID- 17195503
TI  - Returning to practice.

PMID- 17195504
TI  - The practical use of evidence.

PMID- 17195505
TI  - Newly-qualified, enthusiastic midwife? We'll knock it out of you!

PMID- 17195506
TI  - Do you think there should be an agreed ratio of maternity care support
      workers/assistants to midwives and between the allocation and type of tasks?

PMID- 17195507
TI  - [Cooperation between social-psychiatric services and psychiatric hospital-
      expectations and chances of improvement].
AB  - OBJECTIVE: Expectations of social-psychiatric services regarding their
      cooperation with psychiatric hospitals should be examined by qualitative
      research. METHODS: Based upon a content analysis of interviews with nine social
      psychiatric services working in the catchment area of a psychiatric hospital, the
      statements were analysed quantitatively to assess their relative importance.
      RESULTS: Expectations on patient related communication between SpDi and hospital
      staff were expressed most frequently. Further aspects of an "ideal" cooperation
      from the SpDi's point of view are sympathy for each other, information of
      patients, community based psychiatric care, and quality of inpatient care.
      CONCLUSIONS: Social-psychiatric services' expectations represent important clues
      to improve the cooperation at the interface between outpatient and inpatient care
      and should be taken into consideration with respect to continuity of treatment of
      the chronically mentally ill.

PMID- 17195508
TI  - [Outcome quality of gerontopsychiatric day-clinic treatment: changes in life
      satisfaction:].
AB  - OBJECTIVE: The variety of institutional treatments in psychiatry, as well as
      financial aspects make it necessary to evaluate these institutions for the
      quality of their medical care. At the Central Institute of Mental Health in
      Mannheim, the quality of treatment at the geronto-psychiatric day-clinic is
      assessed on the level of outcome quality. METHOD: The patients are examined at
      admission, at discharge, half a year and one year after discharge.
      Psychopathology, activities of daily living, social situation and quality of life
      are assessed by means of standardized instruments. RESULTS: Preliminary results
      show that at discharge, patients are less depressed, have achieved a higher level
      of social activities and contacts and that their quality of life improved in most
      domains. In some domains of quality of life improvement is highly correlated with
      the amelioration of depressive symptoms, in others not. CONCLUSION: Whether these
      effects of treatment will last, has to be studied in follow-up examinations.

PMID- 17195509
TI  - [Prevalence of psychiatric disorders in elderly inpatients of medical and
      surgical departments].
AB  - OBJECTIVE: The aim of the present survey was to study the psychiatric prevalence
      among elderly patients of medical and surgical wards in Austria. METHODS: 244
      inpatients, 60 years and above, were investigated by research psychiatrists using
      the Clinical Interview Schedule. RESULTS: The prevalence was found to be 38.7% in
      medical departments, and 33.0% in surgical departments. According to DSM-III-R
      criteria, dementia (20.9%) and minor depression (7.0%) were the most frequent
      psychiatric categories, followed by substance abuse disorders (4.5%). Among those
      suffering from psychiatric disorders, 68.5% received psychotropics. Only a
      quarter of these drugs were prescribed by consulting psychiatrists, while about
      three quarters were ordered by ward physicians. CONCLUSIONS: These facts
      underline the importance of an intensive cooperation between specialists for
      somatic medicine and psychiatrists.

PMID- 17195510
TI  - [Trial employment: a provisional work setting for psychiatric patients].
AB  - OBJECTIVE: This study investigates the effects of probationary work for
      psychiatric patients in community-based small businesses during their inpatient
      or day care. METHODS: Patients were evaluated for working capacity,
      psychopathology, motivation for work and patient satisfaction (n = 69). RESULTS:
      The results confirm a high degree of acceptance of this approach as well as
      significant improvements on various clinical scales such as the Brief Psychiatric
      Rating Scale (BPRS), the Beck Depression Inventory (BDI), the Global Assessment
      of Functioning Scale (GAF), choice reaction time (Wiener Determinationsgerat,
      WDG), attention (Revisionstest) and self-rating of work-relevant skills.
      CONCLUSIONS: This approach, with its complex demand characteristics, may be an
      effective alternative to occupational therapy, at least for small therapeutic
      units.

PMID- 17195511
TI  - [Quality of life in the course of deinstitutionalisation-- part IV of the Berlin
      Deinstitutionalisation Study].
AB  - As part of the Berlin Deinstitutionalisation Study, quality of life was assessed
      in 142 patients at two points of time. Discharged patients were reassessed one
      year after discharge. Patients who stayed in hospital were reinterviewed 1 1/2-2
      years after the initial assessment. Discharged patients had more leisure
      activities, more often a "good friend", and more frequent social contacts. They
      were less often victim of a crime within the last year. In a cross-sectional
      comparison, they were significantly more satisfied with their life than patients
      who were still in hospital. In the latter group, only satisfaction with mental
      health improved significantly between first and second interview. Discharged
      patients became significantly more satisfied with their life in general, with
      leisure activities, with accommodation, and with mental health between initial
      assessment and follow-up. The findings demonstrate an improvement of quality of
      life in long-term hospitalised patients after discharge.

PMID- 17195512
TI  - [Styles of interpersonal conflict in patients with panic disorder, alcoholism,
      rheumatoid arthritis and healthy controls: a cluster analysis study].
AB  - OBJECTIVE: Conflict and conflict resolution in intimate relationships are not
      only among the most important factors influencing relationship satisfaction but
      are also seen in association with clinical symptoms. Styles of conflict will be
      assessed in patients suffering from panic disorder with and without agoraphobia,
      in alcoholics and in patients suffering from rheumatoid arthritis. METHODS: 176
      patients and healthy controls filled out the Styles of Conflict Inventory and
      questionnaires concerning severity of clinical symptoms. RESULTS: A cluster
      analysis revealed 5 types of conflict management. Healthy controls showed
      predominantely assertive and constructive styles, patients with panic disorder
      showed high levels of cognitive and/or behavioral aggression. Alcoholics showed
      high levels of repressed aggression, and patients with rheumatoid arthritis often
      did not exhibit any aggression during conflict. CONCLUSIONS: 5 Clusters of
      conflict pattern have been identified by cluster analysis. Each patient group
      showed considerable different patterns of conflict management.

PMID- 17195513
TI  - [Assessment of custodial suicide risk--jail and prison suicides in Austria 1975
      1996].
AB  - OBJECTIVE: Although incarceration is a high-risk situation for suicide all over
      the world, hardly any results have been published concerning the situation of
      custodial suicide in German-speaking countries. METHODS: We investigated the case
      notes of all suicides occuring in Austrian prisons between 1975 and 1996 (n=
      207). Beside an evaluation of gender and preferred methods of suicide the suicide
      risk of different circumstances of custody was studied. Suicide rates of
      distinguishable, important subgroups of prisoners were calculated using the
      official statistical data of the Ministry of Justice. RESULTS: The suicide rate
      for people on remand and offenders classified as mentally ill was 231/100,000 vs.
      191/100,000, that was about eight times higher than the suicide rate in Austria's
      general population. The suicide rate for sentenced offenders was 80/100,000,
      about three times as high as the suicide rate in Austria's general population
      (1980-1990: 26.4/100,000). The suicide risk increased with the length of the
      announced sentence. CONCLUSIONS: The suicide rate in custody was highest for
      prisoners on remand and mentally ill offenders. Female offenders had a high
      suicide risk, too. The common assumption that the suicide risk in jails and
      prisons is highest shortly after admission should be confirmed based on better
      methodology or be reconsidered.

PMID- 17195514
TI  - [Contribution to the inheritance of schizophrenic psychosis].
AB  - This case presentation involves a family study looking at the inheritance of
      schizophrenic psychosis. It refers to the increasing risk of disease in
      correlation to the closeness of the relationship. The study includes both
      affected parents, their three children and one grandchild, all of whom had
      multiple hospital admissions and received psychiatric treatment. The clinical
      features were typical of schizophrenia. The severity of illness increased within
      the later generation. This study indicates a high risk correlation in this family
      and is in keeping with other current field studies.

PMID- 17195516
TI  - [Psychiatric symptoms of haemochromatosis in alcohol dependence].

PMID- 17195515
TI  - [Psychiatric illness associated with amphetamines and other stimulants].

PMID- 17195517
TI  - [Bird flu as a global biocatastrophe (editorial)].

PMID- 17195518
TI  - [Clinical significance of intracellular cytokines in patients with yersiniosis].
AB  - AIM: To evaluate clinical value of intracellular content of interferon-gamma (If
      g), IL-2 and IL-4 in different forms of yersiniosis. MATERIAL AND METHODS: The
      number of If-g, IL-2 and IL-4 producing cells was estimated in 35 patients with
      generalized (n = 21, group 1) and secondary-focal (n = 14, group 2) forms of
      yersiniosis. RESULTS: The control over the number of If-g, IL-2 and IL-4
      producing cells in the blood enables valid prognosis of the course and outcome of
      yersiniosis. CONCLUSION: Pathological processes developing in acute yersiniosis
      are based on interleukin-dependent immunopathology.

PMID- 17195519
TI  - [Optimization of hepatoprotective therapy of viral hepatitis with consideration
      of neuromediatory link of pathogenesis].
AB  - AIM: To study therapeutic efficacy of hepatoprotective modalities on the
      experimental hepatitis model and in patients with parenteral hepatitis B and C
      regarding neurogenic amines and their coefficients. MATERIAL AND METHODS: 38
      hepatoprotectors were screened for the highest activity in 1000 white rats with
      toxic hepatitis. Blood catecholamines (CA), histamine (H), serotonin (S), 11
      oxycorticosteroids (11-OCS) were studied in 100 patients with acute hepatitis B
      and C. RESULTS: The recommended hepatoprotectors optimized treatment of
      hepatitis, led to rapid correction of abdominal and dyspeptic syndromes,
      normalization of bilirubin, alkaline phosphatase, cytolysis enzymes levels,
      improvement of neuromediatory balance. Six-month follow-up demonstrated
      improvement of biochemical indices in patients given hepatoprotectors with a
      confirmed action. CONCLUSION: Hepatoprotectors are necessary in pathogenetic
      treatment of acute hepatitis B and C.

PMID- 17195521
TI  - [Time course changes in cytokines content and gas composition in blood of
      patients with salmonellosis and acute shigellosis].
AB  - AIM: To study changes in serum concentrations of interleukines (IL) and tumor
      necrosis factor alpha (TNFa) in the course of acute moderate and severe
      shigellosis and salmonellosis; to elicit their correlation with disorders of gas
      and electrolyte blood composition and acid-base balance (ABB). MATERIAL AND
      METHODS: A total of 39 patients with salmonellosis and 32 patients with acute
      shigellosis admitted to infectious hospital N 2 entered the study. The following
      parameters were assessed: serum concentrations of IL-1, IL-IO and TNFa; ABB, gas
      and electrolyte blood composition; leucocytic intoxication index (LII). The tests
      were made on the disease day 2-3 and 6-7 (in severe salmonellosis on day 10-11).
      RESULTS: In moderate salmonellesis and acute shigellosis the level of
      proinflammatory cytokines (IL-1 and TNFa) diminished while in severe acute
      intestinal infection their concentration was high reflecting imbalance of immune
      response. Content of IL-10 depends on etiology and severity of the course of
      infectious process - the highest IL-10 concentrations were found in patients with
      severe salmonellosis on the disease day 10-11. A direct correlation was confirmed
      between IL-1, TNFa and LII in the disease onset in all patients with acute
      intestinal infections. CONCLUSION: An important role of IL-1, IL-10 and TNFa in
      pathogenesis of bacterial intestinal infections is confirmed. A correlation
      exists between blood gas composition and concentration of cytokines.

PMID- 17195520
TI  - [Acute intestinal infections of virus etiology in adults].
AB  - AIM: To describe clinical symptoms of sporadic cases of noro- and astroviral
      infection in adults; to compare a clinical picture and a course of rotaviral
      infection (R VI), noroviral infection (NVI) and astroviral infection (A VI).
      MATERIAL AND METHODS: Reverse transcription and polymerase chain reaction (RT
      PCR) method was used to examine fecal samples from 1032 patients with acute
      intestinal infections (All) at the age of 15 to 90 years admitted to the
      infectious department of the clinic of Chelyabinsk State Medical Academy in 2004
      2005. Detectability and severity of some symptoms in R VI, NVI and A VI patients
      were analysed and clinical manifestations of viral intestinal monoinfections were
      compared. RESULTS: Monoinfection was diagnosed in 230 (22.3 %)fecal samples: RVI
      (n = 101), NVI (n = 100), A VI (n = 29). Sporadic morbidity was the highest from
      March to May, March to September, October to December for R VI, NVI and A VI,
      respectively. Gastroenteritis syndrome was prevalent in all the infections
      studied. Diarrhea with marked dehydration was more typical for RVI, dyspepsia and
      abdominal pain--for NVI. Intoxication occurred with the same frequency in all the
      infections. Severe RVI ran with normal body temperature in many patients over 60
      years of age. CONCLUSION: Viral diarrheal diseases are frequent in adults of all
      ages and run with similar clinical picture. The most serious course of the
      infection with most severe syndromes of gastroenteritis and dehydration was
      typical for RVI. Etiological nature of viral intestinal infections can be
      established only with laboratory diagnostic methods.

PMID- 17195522
TI  - [Pathogenetic implications of lipid spectrum in some infectious diseases].
AB  - AIM: To estimate concentrations of blood serum lipids and erythrocytic membranes
      in the conditions of intoxication syndrome. MATERIAL AND METHODS: Lipids were
      studied in the serum and erythrocytic membranes of 48 patients with oropharyngeal
      diphtheria and 67 patients suffering from hemorrhagic fever with renal syndrome
      (HFRS) in different forms and severity of the disease. RESULTS: Various
      correlations were found between structural and serum lipids. This is
      pathogenetically important for characterizing biomembranes and variants of
      activation of lipid metabolism in conditions of intoxication syndrome in
      diphtheria and HFRS. CONCLUSION: At the height of diphtheria and HFRS
      organization of biomembrane phospholipids conformation creates conditions for
      cell disorganization.

PMID- 17195523
TI  - [Epidemiology and prophylaxis of septic infectious complications in patients from
      critical and intensive therapy surgical units].
AB  - AIM: To investigate efficacy of the extended complex of preventive and
      antiepidemic measures for reduction of nosocomial infections incidence in
      patients treated in critical and intensive therapy (CIT) surgical units. MATERIAL
      AND METHODS: From 2003 to 2005 CIT units of N.N. Burdenko Central Military
      Hospital conducted a study with participation of 200 patients aged 50 to 77 years
      after extended abdominal operations. The patients were divided into 2 groups.
      Group 1 (n = 100) received standard prophylaxis of infectious complications,
      group 2 (n = 100) received an extended complex of prophylactic and antiepidemic
      measures. First-line antibacterial therapy in all the patients included
      cephalosporines of the third generation and metronidasol. The extended complex
      included air decontamination with application of the system "Clean room complex";
      prevention of nosocomial, particularly ventilator-associated pneumonia (VAP);
      prevention of catheter-associated sepsis; use of disposable sterile items.
      RESULTS: Group I patients developed sepsis in 30%, septic shock and polyorganic
      insufficiency (POI)--in 16% cases; lethality due to infectious complications was
      13%. Gram-negative microflora was dominating. In group 2 sepsis was diagnosed in
      22%, septic shock and POI--in 11%, lethality was 11%. CONCLUSION: The extended
      complex ofpreventive and antiepidemic measures significantly reduced the rate of
      severe infectious complications and related lethality. Among the agents of
      nosocomial infection the percentage of staphylococci and blue pus bacillus
      decreased while that of enterococci and E. coli increased. Contamination of the
      ambient air and CIT units reduced significantly.

PMID- 17195524
TI  - [Differential diagnosis of specific gastric lesions in early syphilis patients
      with helicobacter infection].
AB  - AIM: To evaluate differential-diagnostic significance of different clinical
      signs, endoscopic and serological studies in making diagnosis of early gastric
      syphilis (EGS) in patients with helicobacter infection. MATERIAL AND METHODS:
      Thirty patients were hospitalized with diagnosis of gastric and/or duodenal
      ulcer. Helicobacter pylori was identified morphologically or with a rapid urease
      test. Syphilis was rejected when microprecipitation reaction was negative and
      confirmed with Wassermann reaction. The patients received standard treatment
      including a course of eradication therapy. RESULTS: Endoscopic examination
      discovered single and multiple ulcers in 25 and 5 patients, respectively, located
      in the stomach and duodenum. A rapid test for syphilis produced negative and
      positive results in 28 and 2 patients, respectively. Twenty two patients
      tolerated eradication therapy well. Positive results were achieved in 19 (84.6%)
      patients. Six patients had side effects (pruritus, urticaria, dyspepsia) on
      eradication treatment day 2-3. Jarisch-Herxheimer reaction (elevated body
      temperature 38-38.6 degrees C) and roseola eruption were observed in 2 (6.7%)
      patients with positive serological reactions for syphilis on the first day of
      eradication therapy. CONCLUSION: Diagnostic criteria of EGS are the following:
      serologically confirmed manifest or latent syphilis, poor effect of standard
      antiulcer treatment, rapid elimination of the disease symptoms in antisyphilis
      therapy and positive changes in pathological alterations in gastric mucosa.

PMID- 17195525
TI  - [HCV infection in the elderly].
AB  - AIM: To investigate prevalence, clinical picture and course of hepatitis C virus
      (HCV) infection in elderly patients. MATERIAL AND METHODS: A total of 1045
      patients aged 60- 74 years with chronic diseases of the liver (CDL) were examined
      for hepatitis. RESULTS: HCV monoinfection was detected in 210 (20.1%) patients.
      Alcohol-viral etiology of HCV was revealed in 22% cases. HCV RNA was identified
      in 117 (76%) out of 154 elderly patients. All the HCV infected patients had 1b
      genotype, high viremia. Pain and asthenic syndromes were main clinical
      manifestations of HCV infection. Most often the activity of HCV infection in the
      elderly patients was low (88.6%), progression was slow (94.7%). The latter was
      registered in 22.8% patients. HCV infection in the elderly entails higher
      inflammation activity and incidence of HCV RNA. CONCLUSION: Complex examination
      of elderly patients for early detection of HCV, early diagnosis and treatment
      slows down progression of CDL, reduces the rate of development of severe
      complications and lethality.

PMID- 17195526
TI  - [Clinical features and current laboratory diagnosis of leptospirosis of
      grippotyphosa serogroup].
AB  - AIM: To characterize persistence of the causative agent in the blood of patients
      with leptospirosis, to evaluate significance of the results of polymerase chain
      reaction (PCR) with isolation of ribosomal RNA (rRNA) and microagglutination
      reaction (MAR) in diagnosis of leptospirosis at different stages of the disease.
      MATERIAL AND METHODS: The study included 94 patients with leptospirosis: 51
      (54.2%) males, 43 (45.8%) females, 74 (78. 7%) urban and 20 (21.3%) rural
      citizens in acute leptospirosis, early and late convalescence. Leptospirosis was
      diagnosed on the basis of clinico-epidemiological, laboratory-device data. All
      the patients were divided into 2 groups: with leptospiral jaundice (n = 33,
      35.1%) and without leptospiral jaundice (n = 61, 64.9%). The disease of moderate
      severity was in 64 (68%) patients. Verification of the diagnosis was based on
      determination of specific antibodies titer in MAR using standard set of
      diagnostic cultures. PCR determined rRNA of leptospira in the blood on the
      disease day 5, 10 and 15, 1, 2, 3, 6 and 12 months after the disease onset. The
      results were processed with methods of parametric and non-parametric statistics.
      CONCLUSION: PCR demonstrated diagnostic value in early leptospirosis (sensitivity
      of the method in the disease week 1 was 86%). Diagnostic significance of MAR
      reached 81.8% later - in 3 weeks. Detection of leptospiral rRNA by PCR in the
      autopsy material allows one to recommend this method for additional verification
      of the diagnosis including as an alternative to bacterioscopic test.

PMID- 17195528
TI  - [The role of intravascular autorossette-formation in the onset of anemia in
      patients with chronic cardiac failure].
AB  - AIM: To study intensity of intravascular autorossette-formation (ARF) and its
      role in development of anemia in patients with chronic heart failure (CHF).
      MATERIAL AND METHODS: Blood smears (Romanovsky-Gimze stain) were obtained from
      210 patients with CHF (functional class I-III) treated as indicated. Total number
      of autorossettes (AR) and AR with red cell lysis in them were calculated in the
      blood smears. RESULTS: The number of endogenic AR increases with higher
      functional class of CHF, duration of the disease, number of drugs. With
      increasing number of AR and AR with exocytic lysis, number of red cells and blood
      hemoglobin concentration lower. CONCLUSION: It is suggested that phenomenon of
      intravascular autorossette-formation is involved in pathogenesis of anemia in CHF
      patients and a cause of anemia may be much more complicated that it was thought
      initially.

PMID- 17195529
TI  - [Side effect of granulocytic colony-stimulating factor on the structure and
      function of mouse liver].
AB  - AIM: To study effects of granulocytic colony-stimulating factor (G-CSF) on
      morphology and function of mouse liver. MATERIAL AND METHODS: G-CSF was injected
      subcutaneously to mice in a daily dose 200 mcg/kg for 8 days. Peripheral blood
      formed elements percentage was estimated 24 hours, 7 and 28 days after the last
      injection of G-CSF. Bilirubin level, activity of aspartate- and
      alaninaminotransferase (AST, ALT) were studied in the blood serum. Structure of
      hepatic parenchyma was studied on histological sections stained with hematoxilin
      eosine. The sections were stained with picro-sirius red for detection of
      collagen. RESULTS: G-CSF raised the count of neutrophilic granulocytes in
      peripheral blood. Maximal number of neutrophils in blood was observed on day 7
      after discontinuation of G-CSF. At the same time, hepatocytes were dystrophic and
      partially necrotic. The lumina of many vessels of hepatic lobules were filled
      with erythrocytes. Going in parallel hemolysis of erythrocytes corresponded to
      biochemical indices of functional activity of the liver. Content of AST, but not
      ALT, increased 2-3-fold. Vascular walls were thick due to active synthesis of
      collagen. Four weeks after the last G-CSF injection vascular lumina were free of
      blood, but vascular epithelium layer was thick. CONCLUSION: Side effects of G-CSF
      were found. They affected physiological status of mouse liver causing necrosis of
      hepatosytes, venous plethora and red cell hemolysis. Maximal changes were
      registered on day 7 after discontinuation of G-CSF. The inflammatory process
      (collagen synthesis) continues after 4 weeks upon discontinuation of G-CSF.

PMID- 17195527
TI  - [Diagnosis and treatment of aquired aplastic anemia].
AB  - AIM: To analyse the results of diagnosis and treatment of patients with aquired
      aplastic anemia (AA) in one center. MATERIAL AND METHODS: All AA patients,
      diagnosed and treated in one clinic in 1998-2005, were included in the trial. In
      severe and very severe AA (SAA/VSAA) the patients (n = 19) received combined
      immunosuppressive therapy (IST) with antithymocytic globulin (ATG) and
      cyclosporin A (CsA), in non-severe AA (NSAA) the patients (n = 9) were given
      monotherapy with CsA. Allogenic transplantation of bone marrow (alloTBM) was made
      in 4 young patients with SAA/VSAA. RESULTS: The diagnosis of AA was established
      in 33 patients (19 males and 14 females): NSAA in 9, SAA in 19, VSAA in 5,
      idiopathic--in 26, posthepatic--in 5, associated with pregnancy--in 2 patients.
      Age median was 20 years (13-53). The clone of paroxysmal nocturnal hemoglobinuria
      (PNH) was identified in 7 of 33 patients (21%), antigen HLA-DRB1 *15 in 6 of 11
      patients (55%). In median of 26-month follow-up 31 patients (94%) were alive. In
      IST, complete or partial remissions were obtained in 88% patients. Median of the
      interval to achievement of transfusion independence made up 2.5 months. All the
      patients after alloTBM are in complete remission, chronic extensive transplant
      against host reaction was observed in one case. CONCLUSION: Introduction of
      updated protocols provides long-term survival of more than 80% AA patients. To
      optimize treatment outcomes, it is necessary to include newly diagnosed AA
      patients into ongoing multicenter studies.

PMID- 17195530
TI  - [Clinical and laboratory assessment of endogenic intoxication syndrome in
      patients with rheumatoid arthritis].
AB  - AIM: To detect endogenic intoxication syndrome (EIS) and to assess its severity
      depending on clinical manifestations of rheumatoid arthritis (RA) using
      laboratory tests. MATERIAL AND METHODS: Laboratory tests including analysis of
      synovial fluid, blood count with estimation of leucocytic intoxication index,
      urinalysis, total protein and protein fractions, seromucoid, syalic acids,
      peroxide-antioxidant balance, metabolism of proteoglycanes, immunological tests
      were made in 162 patients with documented RA and 86 healthy controls. Content of
      middle mass molecules served as an integral biochemical EIS marker. RESULTS:
      Inflammatory destructive processes in the affected tissues of RA patients lead to
      marked systemic metabolic and immune disorders accompanied with EIS. Severe EIS
      are associated with severe metabolic disorders. A significantl rise (p < 0.05) in
      content of middle mass molecules in the serum was found in all RA patients
      including in the disease onset and in minimal activity of inflammation and
      presence of only mono-olygoarthritis of the knee joints. CONCLUSION: RA patients
      develop EIS the severity of which depends on the activity and distribution of the
      inflammatory process but not on the disease stage. Metabolic disorders in RA
      patients can be assessed with an effective method--blood serum middle mass
      molecule assay.

PMID- 17195531
TI  - [The role of fat tissue in development of metabolic disorders in patients with
      diabetes mellitus type 2 and obesity].
AB  - AIM: To specify changes in clinicolaboratory parameters in reduction of obesity
      in patients with diabetes mellitus type 2 (DM-2). MATERIAL AND METHODS:
      Antropometry, densitometry of fat tissue (FT) were made and parameters of fat and
      carbohydrate metabolism (lipidogram, glycated hemoglobin, immunoreactive
      insulin), FT secretory activity (leptin, adiponectin, TNF-alpha) were studied in
      75 obese DM-2 patients. After the above primary examination all the patients were
      randomized into 2 groups: group 1 (n = 55) received xenical (120 mg 3 times a
      day) and kept moderate hypocaloric diet; group 2 (n = 20) received only the above
      diet therapy. Active treatment lasted 24 weeks. RESULTS: In addition to symptoms
      of metabolic syndrome (MS) the patients were found to have secretory disturbances
      of FT activity: elevation of leptin and TNF-alpha levels, subnormal adiponectin.
      These alterations directly correlated with body mass, FT mass gain, increase in
      waist circumference. Hyperleptinemia, hyperinsulinemia and hypoadiponectinemia
      were considered as markers of insulin resistance (IR) and related conditions.
      Xenical promoted a significant weight loss resulting in a positive trend in the
      parameters of adipokines, fat and carbohydrate metabolism, in reduction of IR.
      CONCLUSION: Xenical is beneficial for patients with DM-2 and obesity because it
      improves metabolic processes.

PMID- 17195533
TI  - [Combined antiviral treatment of a patient with chronic mixed hepatitis (HBV +
      HCV)].

PMID- 17195532
TI  - [Catalytic autoantibodies--a new molecular instrument in cardiology and
      ophthalmology].
AB  - AIM: To develop a conceptual model of using catalytic autoantibodies as
      diagnostic and monitoring tools in organ-specific autoimmune disorders. MATERIAL
      AND METHODS: A total of 99 patients (56 males and 43 females aged 21-52 years)
      with autoimmune myocarditis (AM) and 198 patients (77 males and 121 females aged
      8-79 years) with autoimmune uveitis (A U) participated in the study. AM patients
      were examined for anticardiomyosin and anti-DNA autoantibodies (ACM, ADNAab), AU
      patients - for autoantibodies to S-antigen, IRBP, redopsin, phosphocine, autoDNA.
      RESULTS: AM patients had double level of DNA-binding autoantibodies. In 1/3 of
      them there was hydrolysing DNA and cytotoxic activity. In AU patients maximal
      titers were in Behcet's disease, sympathic ophthalmia, generalized uveitis and
      viral uveitis. CONCLUSION: Autoantibodies with different specificity and function
      including DNA-abzymes can be additional diagnostic and prognostic markers.

PMID- 17195534
TI  - [Periodic disease in a patient with admittance diagnosis yersiniosis].

PMID- 17195535
TI  - [Opportunistic infections in HIV-infected subjects: no wonders].

PMID- 17195536
TI  - [Cases of trichinellesis in citizens of Moscow].

PMID- 17195538
TI  - [Effects of depressive disorders on development and outcome of cardiovascular
      diseases].

PMID- 17195537
TI  - [Fat hepatosis].

PMID- 17195539
TI  - [Bronchodilating long-acting drugs in the treatment of stable chronic obstructive
      pulmonary disease. Analysis of the latest data].

PMID- 17195541
TI  - [Systematic approach to family nursing: thoughtful considerations].
AB  - This study is part of the theoretical referential of doctorate in development
      thesis based on Bertalanffy, Vasconcellos and Capra's ideas. It searches from the
      systemic approach to comprehend the family as a inter-relations system among the
      members, an irreducible open unit to the continuous flow of entrance and exit of
      energy, a dynamic unit in which the whole and the parts are influenced mutually.
      It aims the development of a professional reflection for the Care of Nursing for
      the family not as context, but the familiar one. Its genesis is related to the
      many concerns that have surfaced from professional activities which have met
      answers in the new paradigmatic approach of the post-modern science of the
      complexity, instability, intersubjectiveness for the think/act of Nursing in the
      interdisciplinary development of their careful actions of joint way: the unit
      family.

PMID- 17195540
TI  - [Spirituality, source of hope, for a humanized future].

PMID- 17195542
TI  - [Thinking education: attempt to define values and models of behavior].

PMID- 17195543
TI  - [Feelings, emotions and passion in babies].

PMID- 17195544
TI  - [Experience with a terminal situation in oncologic disease].

PMID- 17195545
TI  - [The training "phantoms". Life history as a training method].

PMID- 17195546
TI  - [Proprioceptive reeducation].

PMID- 17195547
TI  - [The role of the nurse at the Service of Alcoholism Treatment: from assisting to
      rendering autonomous].

PMID- 17195548
TI  - [Stem cells-- an effective alternative].

PMID- 17195549
TI  - Proper concent for treatment.

PMID- 17195550
TI  - Merging views and collaboration are trends in health care.

PMID- 17195551
TI  - MSMS: inventing the future.

PMID- 17195552
TI  - How well does your insurer defend malpractice claims?

PMID- 17195553
TI  - Effective communication can reduce liability risk.

PMID- 17195554
TI  - International research on arsenic contamination and health.

PMID- 17195555
TI  - An eight-year study report on arsenic contamination in groundwater and health
      effects in Eruani village, Bangladesh and an approach for its mitigation.
AB  - Based on several surveys during 1997-2005 and visits of a medical team to Eruani
      village, Laksham upazila, Comilla district, Bangladesh, the arsenic contamination
      situation and consequent clinical manifestations of arsenicosis among the
      villagers, including dermatology, neuropathy, and obstetric outcome, are reported
      here. Analysis of biological samples from patients and non-patients showed high
      body burden of arsenic. Even after eight years of known exposure, village
      children were still drinking arsenic-contaminated water, and many of them had
      arsenical skin lesions. There were social problems due to the symptoms of
      arsenicosis. The last survey established that there is a lack of proper awareness
      among villagers about different aspects of arsenic toxicity. The viability of
      different options of safe water, such as dugwells, deep tubewells, rainwater
      harvesting, and surface water with watershed management in the village, was
      studied. Finally, based on 19 years of field experience, it was felt that, for
      any successful mitigation programme, emphasis should be given to creating
      awareness among villagers about the arsenic problem, role of arsenic-free water,
      better nutrition from local fruits and vegetables, and, above all, active
      participation of women along with others in the struggle against the arsenic
      menace.

PMID- 17195556
TI  - Arsenic contamination in groundwater: a global perspective with emphasis on the
      Asian scenario.
AB  - The incidence of high concentrations of arsenic in drinking-water has emerged as
      a major public-health problem. With newer-affected sites discovered during the
      last decade, a significant change has been observed in the global scenario of
      arsenic contamination, especially in Asian countries. This communication presents
      an overview of the current scenario of arsenic contamination in countries across
      the globe with an emphasis on Asia. Along with the present situation in severely
      affected countries in Asia, such as Bangladesh, India, and China, recent
      instances from Pakistan, Myanmar, Afghanistan, Cambodia, etc. are presented.

PMID- 17195557
TI  - Arsenic exposure and its impact on health in Chile.
AB  - The problem of arsenic in Chile was reviewed. In Chile, the population is exposed
      to arsenic naturally via drinking-water and by air pollution resulted from mining
      activities. The sources of arsenic were identified to estimate the exposure of
      population to arsenic through air, water, and food. Health effects, particularly
      early effects, observed in children and adults, such as vascular diseases
      (premature cardiac infarct), respiratory illnesses (bronchiectasis), and skin
      lesions have been described. Chronic effects, such as lung and bladder cancers,
      were reported 20 years after peak exposure and persisted 27 years after
      mitigation measures for removing arsenic from drinking surface water were
      initiated. Although the effects of arsenic are similar in different ethnic and
      cultural groups (e.g. Japanese, Chinese, Indian, Bangladeshi, American, and
      Taiwanese), variations could be explained by age at exposure, the dose received,
      smoking, and nutrition. Since health effects were observed at arsenic levels of
      50 microg/L in drinking-water, it is advised that Chile follows the World Health
      Organization's recommendation of 10 microg/L. The Chilean experience in removal
      of arsenic suggests that it is feasible to reach this level using the
      conventional coagulation process.

PMID- 17195558
TI  - Current research problems of chronic arsenicosis in China.
AB  - Chronic arsenicosis is a newly-emerged public-health issue in China and many
      other Asian countries. Over 200 million people are estimated to be at the risk of
      high arsenic exposure from drinking-water in the Asian region. To protect people
      from the hazards of chronic arsenic poisoning, the Chinese Government has been
      providing low-arsenic drinking-water to some seriously-affected rural areas, such
      as Inner Mongolia autonomous province. Results of follow-up studies showed that
      both the average values of arsenic, including inorganic arsenic (iAs),
      monomethylated arsenic, dimethylated arsenic and trimethylated arsenic, and 8
      hydroxydeoxyguanine in urine, decreased significantly after drinking low-arsenic
      water for one year, and arsenic-specific skin lesions also improved to some
      extent. However, a five-year follow-up study showed no more significant
      improvement of skin lesions, while the potential risk of arsenic-induced cancers
      after cutting off high-arsenic exposure was still uncertain and indefinite. The
      susceptibility of children compared to adults to chronic arsenic exposure and the
      need to re-evaluate the appropriate standard of arsenic in drinking-water were
      also discussed in this paper.

PMID- 17195559
TI  - Association between chronic exposure to arsenic and slow nerve conduction
      velocity among adolescents in Taiwan.
AB  - The association between chronic exposure to arsenic and peripheral neuropathy has
      been controversial in previous studies, which may be due to the influence of
      factors, such as age, gender, chronic diseases, occupational injuries, and
      arsenic exposure. To clarify the question of this association, a cross-sectional
      study was designed. In total, 130 junior high school students aged 12-14 years
      were included and examined for the motor and sensory nerve conduction velocity of
      peripheral nerves in their right-upper and lower limbs. Concentrations of arsenic
      in well-water and history of drinking well-water were retrieved from a baseline
      database created in 1991. After adjustment for gender and height, a significant
      odds ratio of 2.9 (95% confidence interval [CI] 1.1-7.5) was observed for the
      development of slow nerve conduction velocity of the sural sensory action
      potential (SAP) among the study subjects with a cumulative arsenic dosage
      of>100.0 mg. In addition, a borderline statistical significance with odds ratio
      of 7.8 (95% CI 1.001-69.5) for the development of slow nerve conduction velocity
      of sural SAP was also observed among the study subjects who drank well-water
      containing arsenic concentrations of >50.0 microg/L and with a cumulative arsenic
      dosage of >100.0 mg. The study found that chronic exposure to arsenic might
      induce peripheral neuropathy. It also found that the slowing of the nerve
      conduction velocity of sural SAP might be an early marker of chronic arsenic
      neuropathy.

PMID- 17195560
TI  - Arsenic in drinking-water and reproductive health outcomes: a study of
      participants in the Bangladesh Integrated Nutrition Programme.
AB  - This study examined 2,006 pregnant women chronically exposed to a range of
      naturally-occurring concentrations of arsenic in drinking-water in three upazilas
      in Bangladesh to find out relationships between arsenic exposure and selected
      reproductive health outcomes. While there was a small but statistically
      significant association between arsenic exposure and birth-defects (odds
      ratio=1.005, 95% confidence interval 1.001-1.010), other outcomes, such as
      stillbirth, low birth-weight, childhood stunting, and childhood under-weight,
      were not associated with arsenic exposure. It is possible that the association
      between arsenic exposure from drinking-water and birth-defects may be a
      statistical anomaly due to the small number of birth-defects observed. Future
      studies should look more closely at birth-defects, especially neural tube
      defects, to elucidate any potential health effects associated with arsenic
      exposure from drinking-water. Further, given the knowledge that serious health
      effects can result from chronic arsenic exposure, efforts to find alternatives of
      safe drinking-water for the population must continue.

PMID- 17195561
TI  - Association of arsenic-contaminated drinking-water with prevalence of skin cancer
      in Wisconsin's Fox River Valley.
AB  - During July 2000-January 2002, the Wisconsin Division of Public Health conducted
      a study in 19 rural townships. A high percentage of private drinking-water wells
      in these townships contained traces of arsenic. Residents were asked to collect
      well-water samples and complete a questionnaire regarding residential history,
      consumption of drinking-water, and family health. In total, 2,233 household wells
      were tested, and 6,669 residents, aged less than one year to 100 years, provided
      information on water consumption and health. The well-water arsenic levels ranged
      from less than 1.0 to 3,100 microg/L. The median arsenic level was 2.0 microg/L.
      The arsenic levels were below the federal drinking-water standard of 10 microg/L
      in 80% of the wells, while 11% had an arsenic level of above 20 microg/L. Of
      residents aged over 35 years, those who had consumed arsenic-contaminated water
      for at least 10 years were significantly more likely to report a history of skin
      cancer than others. Tobacco use was also associated with higher rates of skin
      cancer and appeared to synergize the effect of arsenic on the development of skin
      cancer.

PMID- 17195562
TI  - Levels of arsenic in drinking-water and cutaneous lesions in Inner Mongolia.
AB  - The most common health effects from drinking-water containing dissolved arsenic
      are skin abnormalities and lesions that are typically diagnosed as keratosis and
      pigment disorder. It was previously reported that the prevalence of cutaneous
      lesions was about 44% in arsenic-affected villages. However, there has been
      little research on the relationship between levels of arsenic in drinking-water
      and cutaneous lesions in Inner Mongolia. One study examined the association
      between the prevalence of keratosis and levels of arsenic exposure and the
      relationship between pigment disorder and levels of arsenic exposure among
      villagers aged 18 years or older in the arsenic-affected village of Hetao Plain
      in Inner Mongolia, PR China. The study included 227 participants who were
      affected by cutaneous lesions and 221 participants who were not affected by
      cutaneous lesions diagnosed in 1996 and 1998. Well-water drunk by the
      participants was collected to analyze arsenic content. Adjusting for age, sex,
      and smoking, logistic regression was applied to calculate the risks that arsenic
      in drinking-water will lead to cutaneous lesions. The results from the logistic
      regression showed that, with the increase of arsenic concentration in water, the
      risk of pigment disorder also increased (odds ratio [OR]=5.25, 95% confidence
      interval [CI] 1.32-83.24 for 50-199 microg/L; OR=10.97, 95% CI 1.50-79.95 for 200
      499 [microg/L; OR=10.00, 95% CI 1.39-71.77 for > or = 500 microg/L (p=0.000), but
      the association between risk of keratosis and levels of arsenic was not
      significant (p=0.346). The findings suggest that keratosis is an early feature of
      arsenic poisoning, and the development of pigment disorder depends on higher
      doses of arsenic intake rather than keratosis. Further studies are needed to
      confirm that cutaneous lesions and other adverse health effects occur at low
      levels of arsenic exposure.

PMID- 17195563
TI  - Electrocardiographic abnormalities among arsenic-exposed persons through
      groundwater in Bangladesh.
AB  - This study was carried out among arsenic-exposed and non-exposed people of
      Bangladesh to assess and compare their cardiac status based on
      electrocardiographic (ECG) findings. For the purpose of the study, participants
      were included in three groups: arsenic-exposed persons with arsenicosis
      (arsenicosis group), arsenic-exposed persons without arsenicosis (non-arsenicosis
      group), and persons not exposed to arsenic (non-exposed group). Each group
      included 50 respondents. In this study, no significant difference in heart rate,
      rhythm, axis, and pulse rate interval was detected among the arsenicosis, non
      arsenicosis and non-exposed groups. A significant difference in corrected QT
      interval between the arsenicosis and the non-exposed group (p<0.05) was observed.
      On the contrary, no statistically significant difference in corrected QT interval
      between the non-arsenicosis and the non-exposed group was found. Abnormal QRS
      complex was found among 14%, 8%, and 2% of the arsenicosis, non-arsenicosis, and
      non-exposed groups respectively. ECG findings, indicative of left ventricular
      hypertrophy, ischaemic heart disease, and right bundle branch block, were high
      among the arsenicosis group. Overall, abnormal ECG findings were high (58%) among
      the respondents of the arsenicosis group and were highly significant (p<0.001).
      The findings revealed that there was a significant association between ECG
      abnormalities and arsenic exposure.

PMID- 17195564
TI  - Prevalence of arsenic-related skin lesions in 53 widely-scattered villages of
      Bangladesh: an ecological survey.
AB  - A survey was carried out to provide a representative assessment of prevalence and
      risk of arsenic-related skin lesions in relation to geographical distribution of
      arsenic in wells of rural Bangladesh as a necessary background for research into
      effects in pregnancy and cancer risks. A systematic random sample of 53 villages
      in four divisions of Bangladesh served by Gonoshasthaya Kendra was selected, and
      all women aged 18 years or more (n=16,740) were listed. Trained paramedics
      recorded the presence of skin thickening and nodules on the palms and soles,
      together with information on tubewell use. The prevalence was related to the mean
      concentration of arsenic for the district as indicated by data from the British
      Geological Survey and to the date the first well in the village was installed.
      Overall, the observed prevalence was 176 cases (1.3%) in 13,705 women examined,
      varying from 0% in 26 villages to 23% in one; lesions were observed more
      frequently on hands than on feet. The estimate doubled with concentrations of
      arsenic from 11 to < or =50 microg/L and increased more than 20 times at >50
      microg/L. In the absence of further information, priority for control measures
      should be directed at areas where the average concentrations of arsenic are above
      50 microg/L, especially in villages where skin lesions have been identified.

PMID- 17195565
TI  - Arsenic exposure in pregnancy: a population-based study in Matlab, Bangladesh.
AB  - This study assessed the exposure of pregnant women to arsenic in Matlab,
      Bangladesh, an area with highly-elevated concentrations of arsenic in tubewells,
      by measuring concentrations of arsenic in urine. In a defined administrative
      area, all new pregnancies were identified by urine test in gestational week 6-8,
      and women were asked to participate in the assessment of arsenic exposure. Urine
      for analysis of arsenic was collected immediately and in gestational week 30. In
      total, 3,426 pregnant women provided urine samples during January 2002-March
      2003. There was a considerable variation in urinary concentrations of arsenic
      (total range 1-1,470 microg/L, adjusted to specific gravity 1.012 g/mL), with an
      overall median concentration of 80 microg/L (25th and 75th percentiles were 37
      and 208 microg/L respectively). Similar concentrations were found in gestational
      week 30, indicating no trend of decreasing exposure, despite the initiation of
      mitigation activities in the area. Arsenic exposure was negatively associated
      with socioeconomic classes and achieved educational level. There were marked
      geographical variations in exposure. The results emphasize the urgent need for
      efficient mitigation activities and investigations of arsenic-related
      reproductive effects.

PMID- 17195566
TI  - Prevalence of arsenicosis in terai, Nepal.
AB  - This paper summarizes the findings of surveys on arsenicosis cases conducted
      during 2001-2004 in terai, Nepal, by governmental and non-governmental
      organizations in their respective project areas and by some national and
      international institutes. Studies were conducted in six arsenic-contaminated
      districts of terai, namely Nawalparasi, Bara, Parsa, Rautahat, Rupandehi, and
      Kapilvastu. In these districts, arsenic contamination in tubewells varied from
      2.1% to 25.7%. The prevalence of arsenicosis was, on average, 2.2% and varied
      from 0.7% in Kapilavastu district to 3.6% in Nawalparasi district. In the
      community-based study, the highest prevalence (18.6%) of arsenicosis was found in
      Patkhouli village of Nawalparasi, where 95.8% of tubewells were contaminated with
      arsenic. The prevalence of arsenicosis was higher in older age-groups (>50 years)
      of both the sexes. Males suffered more from arsenicosis than females (odds ratio:
      2.50, 95% confidence interval 1.80-3.47). Skin manifestations, such as melanosis
      and keratosis, were the common symptoms of arsenicosis. Most patients were
      identified in the early or mild stage of the disease. They are expected to
      recover if further exposure to arsenic could be avoided by providing arsenic-safe
      drinking-water through intervention measures.

PMID- 17195567
TI  - Arsenic exposure from drinking-water and carotid artery intima-medial thickness
      in healthy young adults in Bangladesh.
AB  - Epidemiological studies have linked high levels (>200 microg/L) of chronic
      exposure to arsenic in drinking-water with elevated risks of several vascular
      diseases. In this pilot study, the association between low-level arsenic exposure
      and carotid artery intimal-medial thickness (IMT) was evaluated among 66 healthy,
      normotensive, relatively young individuals (mean age 35 years) participating in
      the ongoing Health Effects of Arsenic Longitudinal Study in Bangladesh.
      Participants with a higher carotid IMT (>0.75 mm) in general had higher levels of
      past chronic exposure of arsenic than those with a lower carotid IMT (< or = 0.75
      mm). Although the differences in average arsenic exposure between the two groups
      were not statistically significant, the findings suggest a possible association
      between low-level arsenic exposure from drinking-water and carotid
      atherosclerosis, warranting the need for larger studies.

PMID- 17195568
TI  - A matter of life.

PMID- 17195569
TI  - Alleviating the pain.

PMID- 17195570
TI  - An indiscriminating culprit. Improving prognosis in stroke survivors.

PMID- 17195571
TI  - Harnessing energy.

PMID- 17195572
TI  - In the swim.

PMID- 17195573
TI  - A position of strength.

PMID- 17195574
TI  - An ounce of prevention.

PMID- 17195575
TI  - Psychosocial and psychodynamic factors influencing health care utilisation.
AB  - This paper aims to elucidate some dysfunctional aspects of health care
      utilisation by combining concepts from modern systems theory and from
      psychoanalysis. Contemporary health care in industrialised countries can be
      conceived as a social system in terms of modern systems theory. According to this
      theory, social systems are operating on the basis of a 'guiding difference,'
      which in the case of health care is the distinction between 'healthy' and 'ill.'
      Its rigidity in adhering to the healthy-ill dichotomy exposes health care to
      being collusively entangled in the interpersonal defence arrangements of
      patients. In the psychoanalytic view, individual conflicts can be warded off from
      consciousness not only by intrapsychic defence, but also by interpersonal defence
      mechanisms. These mechanisms involve the patients' close social environment,
      often including doctors and hospitals. The functioning and the motivational
      structure of health care itself shows features of neurotic defence: not only its
      representatives, but health care as a whole act in a rigid, obsessive manner in
      order to separate the healthy from the ill and to battle against (presumed)
      diseases. This obsession sometimes results in excessive diagnostic activism and
      in inconsiderate application of aggressive medical treatments. Both are
      inappropriate with regard to the salient problem of modern medicine: the increase
      of chronic nonfatal diseases like depression and chronic pain. The described
      defence mechanisms are unconscious not only to patients but also to health care
      professionals (let alone health politicians), and are contributing to
      dysfunctional health care overuse.

PMID- 17195576
TI  - Reimbursement decision-making and prescription patterns of glitazones in
      treatment of type 2 diabetes mellitus patients in Denmark.
AB  - There are marked differences between countries with regard to reimbursement
      decision-making, yet few studies have tried to understand this process and its
      consequences by a detailed analysis of the local context and decision-making
      structure. This article describes reimbursement decision-making and subsequent
      prescribing patterns of new pharmaceuticals by means of a case study on
      glitazones in treatment of type 2 diabetes mellitus patients in Denmark. The
      study shows that institutional arrangements, providing the context in which
      evidence is used, are highly important for understanding the reimbursement
      decision-making process. In particular the Danish Medicines Agency (DMA) has
      shaped the decision to reimburse glitazones on the basis of physician-mediated
      requests of individual patients. Relatively few patients have been prescribed
      glitazones since their introduction in 2000, suggesting that individual
      reimbursement may be an effective instrument in controlling overall expenditure
      of selected pharmaceuticals, although in the case of glitazones this has likely
      been achieved at the expense of equality in access to the products. The
      discussion focuses on the generalizability of the findings to both other
      pharmaceuticals in the individual reimbursement scheme in Denmark, and to other
      countries that are trying to balance the need to control overall pharmaceutical
      care expenditure with the need to secure equality in access to new drugs with
      therapeutic added value.

PMID- 17195577
TI  - Analysing structural and cultural change in acute settings using a Giddens-Weick
      paradigmatic approach.
AB  - An examination of the salient literature on hospital clinical directorates (CDs)
      is presented. A critique of the largely managerialist, instrumental, hortatory
      and normative extant literature about CDs is offered. In analysing the literature
      this way the earlier promotional and critical literature is eschewed in favour of
      an evaluative approach. CDs are then reconceptualised by locating them within two
      overarching accounts of social structure--formalised, prescribed frameworks, and
      enacted, patterned interactions--following the kinds of distinctions made by
      Giddens, Weick, social action and institutional theorists. Social structure as it
      relates to culture is also considered, following Martin. Such an approach
      facilitates an understanding of the general weaknesses of health service
      perspectives and methods of analysis, and exposes the strengths of Giddens-Weick
      type paradigms.

PMID- 17195578
TI  - Why sports medicine is not medicine.
AB  - Sports Medicine as an apparent sub-class of medicine has developed apace over the
      past 30 years. Its recent trajectory has been evidenced by the emergence of
      specialist international research journals, standard texts, annual conferences,
      academic appointments and postgraduate courses. Although this field of enquiry
      and practice lays claim to the title 'sports medicine' this paper queries the
      legitimacy of that claim. Depending upon how 'sports medicine' and 'medicine' are
      defined, a plausible-sounding case can be made to show that sports medicine is
      not in fact a branch of medicine. Rather, it is sometimes closer to practices
      such as non-therapeutic cosmetic surgery. The argument of the paper is as
      follows. It begins with a brief statement concerning methodology. We then
      identify and subscribe to a plausible defining goal of medicine taken from a
      recognised authority in the field. Then two representative, authoritative,
      definitions of sports medicine are discussed. It is then shown that acceptance of
      these definitions of sports medicine generates a problem in that if they are
      accepted, no necessary commitment to the defining goal of medicine is present
      within sports medicine. It seems to follow that sports medicine is not medicine.
      In the final part of the paper a critical response to that conclusion is
      presented and rebutted. The response is one which rejects the identification of
      the defining goal of medicine upon which our argument rests.

PMID- 17195579
TI  - Principles help to analyse but often give no solution--secondary prevention after
      a cardiac event.
AB  - The aim of this paper is to investigate whether or not ethical conflicts can be
      identified, analysed and solved using ethical principles. The relation between
      the physician and the patient with ischemic heart disease (IHD) as life style
      changes are recommended in a secondary prevention program is used as an example.
      The principal persons affected (the patient and his or her spouse) and the
      ethical principles (respect for autonomy, non-maleficence, beneficence and
      justice) are combined in a two dimensional model. The most important person
      affected by the recommendations is the patient. His or her autonomy is challenged
      by the suggested life style changes, the purpose of which is to promote the
      future wellbeing and health of the patient. The spouse is indirectly involved in
      and affected by the process. He or she often feels neglected by caregivers.
      Ethical conflicts can both be identified and analysed using ethical principles,
      but often no solution is implied. Most (if not all) physicians would strongly
      encourage life style changes, but surprisingly there is no uncontroversial
      justification for this conclusion using principles.

PMID- 17195581
TI  - [Extrapulmonary tuberculosis in Russia: official statistics and reality].

PMID- 17195580
TI  - Is there any ideal of 'high quality care' opposing 'low quality care'? A
      deconstructionist reading.
AB  - The expressions 'high quality care' and 'low quality care' are cognitive and
      linguistic artefacts that help to structure people's lives and thinking; for
      example, moves are now afoot internationally to pay bonuses to health
      professionals for delivering high quality care. United States programmes, most
      conspicuously, are assuming that high quality care can be validly distinguished
      from low quality care, and incentivised through bonuses. This distinction is
      always at least implicit, for high quality care has no meaning without low
      quality care. Through a 'deconstructionist reading,' this article discusses
      limitations of categorising the quality of care as either high or low. The
      limitations of this 'binary opposition' can include a lack of defining
      attributes; vagueness and fuzziness at the 'boundaries' between high quality care
      and low quality care; concealment of quality as a continuum; and use of the
      binary opposition to effect social order and control. Health policy implications
      of our analysis are discussed. Drawing upon the general medical services contract
      in the United Kingdom, we suggest an approach to overcoming the
      oversimplification and imprecision that categorisation tends to produce.

PMID- 17195582
TI  - [Current radiotherapy for extrapulmonary tuberculosis].
AB  - Radiation studies are prominent in the diagnosis of extrapulmonary tuberculosis.
      X-ray study preserves its basic value. Its-based concepts of the pathology of
      osteoarticular, urogenital, lymphabdominal tuberculosis largely allow for
      analyzing the images obtained by new medical visualization techniques, such as X
      ray tomography, computed tomography, magnetic resonance imaging, ultrasonography,
      and radionuclide studies. Each method has its merits and demerits and is used by
      a certain algorithm at different sites of extrapulmonary tuberculosis.

PMID- 17195584
TI  - [Adenosine deaminase in the complex diagnosis of different forms of
      extrapulmonary tuberculosis].
AB  - The paper summarizes the results of studies of the activity of adenosine
      deaminase (ADA) in biological fluids (including that during tuberculin tests) as
      a tool for the differential diagnosis of different forms of extrapulmonary
      tuberculosis, such as pleuritis, synovitis, meningitis, tuberculosis of female
      genitals and peripheral lymph nodes, and uveitis. The threshold for the activity
      of ADA or the magnitude of its increase in antigenic stimulation, which provides
      the optimum ratio of the sensitivity to specificity of the tests and their
      maximum diagnostic efficiency, are given. The optimization of diagnosis of
      tuberculous synovitis is shown to facilitate the study of ADA activity
      concomitantly with the determination of the level of antituberculosis antibodies.
      The tests under discussion are economically sound and yield results in several
      hours and, in case of a provocative test, in 3 days.

PMID- 17195583
TI  - [Clinical, x-ray, and laboratory features of tuberculosis and osteomyelitis of
      the spine].
AB  - In 20% of cases, tuberculous spondylitis running with a prevalence of the
      exudative-necrotic type of a local tissue reaction has an acute onset with
      febrile fever, severe pains, and progressive neurological disorders and
      clinically resembles acute hematogenous osteomyelitis of the spine. With a
      predominance of the productive type of a tissue reaction, tuberculous spondylitis
      resembles subacute hematogenous osteomyelitis of the spine. History data,
      laboratory parameters, and an X-ray follow-up are of great importance in its
      differential diagnosis.

PMID- 17195585
TI  - [The specific features of bacterial isolation and drug resistance of Mycobacteria
      in extrapulmonary tuberculosis].
AB  - The reduced viability and enzymatic activity of the pathogen from the foci of
      extrapulmonary tuberculosis are twice more frequently than those in pulmonary
      tuberculosis. The isolation of mycobacterial L-forms and the use of polymerase
      chain reaction significantly enhance the efficiency of the etiological diagnosis
      of extrapulmonary tuberculosis. There are extremely poor trends for drug
      resistance to develop in mycobacteria, in 2005 the rate of which was 92.5% in
      pulmonary tuberculosis and 83.4% in extrapulmonary tuberculosis. However,
      multidrug resistance is much less common in extrapulmonary tuberculosis than in
      pulmonary tuberculosis; the rates were 33.9 and 73.9%, respectively. Levofloxacin
      resistance was also completely preserved so the reserves for the treatment of
      extrapulmonary tuberculosis are higher than those in pulmonary tuberculosis.

PMID- 17195586
TI  - [Study of rifampicin resistance in L-forms of Mycobacterium tuberculosis, by
      analyzing rpoB gene mutations].
AB  - Twenty-nine Mycobacterium tuberculosis (MBT) L-form strains isolated from biopsy
      and surgery samples taken in 27 patients with extrapulmonary tuberculosis were
      studied. Since a direct examination of the resistance of L-forms is impossible
      due to their in vitro culturing features, it is expedient to use molecular
      genetic methods, by studying rpoB gene mutations. The study showed a high
      mutation rate (89.7%) in MBT L-forms associated with rifampicin resistance. The
      findings correlate with the recent years' monitoring of drug resistance in MBT in
      extrapulmonary tuberculosis, which has indicated that the total resistance of MBT
      from the foci of this form of tuberculosis to antituberculous drugs is as high as
      90% and multidrug resistance is 30%. Moreover, the mycobacterial population was
      found to be heterogeneous. The ratio of rifampicin-resistant L-forms to sensitive
      ones in the established heterogeneity of the mycobacterial population calls for
      further studies.

PMID- 17195587
TI  - [Basic directions in enhancing the efficiency of the diagnosis and treatment of
      ocular tuberculosis].
AB  - The paper describes the basic methods for the diagnosis and treatment of ocular
      tuberculosis, which are based on the studied mechanisms of its pathogenesis. It
      updates the pathomorphism of the disease, the results of experimental studies
      dealing with new diagnostic techniques, including an objective estimation of a
      focal response to tuberculin. The results of studies of ocular tuberculosis in
      children, as well as the efficacy of the new Russian immunotropic drugs glutoxim
      and betaleukin are outlined.

PMID- 17195588
TI  - [Posteriorinstrumental spinal fixation in tuberculous spondylitis and
      osteomyelitis of the vertebral bodies].
AB  - The short- and long-term results of surgical treatment were studied in 74
      patients with tuberculous spondylitis and in 20 patients with chronic
      osteomyelitis of the vertebral column. All the patients underwent radical
      reconstructive operations on the anterior vertebral column if they had an active
      inflammatory process. The operations were supplemented by an interstitial
      posterior instrumental fixation with the Hurrington manipulation reduction frames
      or the plates, developed at the Central Institute of Traumatology and
      Orthopedics, in 11 cases and with the Cotrel-Dubosse tools in 28 cases. The
      Cotrel-Dubosse tools were shown to have significant advantages in correcting
      kyphosis and preventing graft resorption and chronic pain syndrome in tuberculous
      spondylitis.

PMID- 17195589
TI  - [Elastic materials in surgery for inflammatory diseases of the vertebral column].
AB  - When 17 patients were surgically treated for spinal tuberculosis and
      osteomyelitis, anterior spine fusion was performed by A. Ye. Garbuz's procedure
      that was based on the replacement of a spinal defect by a carbon-carbonic implant
      that had rifampicin containers in the frontal sections, as well as by autologous
      bone grafts. The carbon-carbonic implants reliably fix an operated spinal
      portion, prevent the progression of kyphotic deformity, and create good
      conditions for autologous bone grafts to knit. An osteocarbonic block forms in
      the late postoperative period.

PMID- 17195590
TI  - [Recovery of the support capacity of the vertebral column in patients with
      tuberculous spondylitis].
AB  - The paper presents the results of anterior spine fusion in 250 patients with
      tuberculous spondylitis involving 2 to 8 vertebrae, by using free and non-free
      autologous bone grafts, carbonaceous implants, and revascularized transplants.
      Anterior spine fusion added to posterior spinal fixation with a CD-type metal
      construction. A tuberculous process in the spine was cured in 96.1% of cases; the
      spinal support capability recovery rate was 95.2% in the early postoperative
      period and in 93.5% in the late one.

PMID- 17195591
TI  - [Changed life quality in patients with tuberculosis and other diseases of large
      joints after surgical treatment].
AB  - The quality of life was studied in 88 patients who had been operated on for
      tuberculosis and other diseases of the hip and knee joints. Reconstructive
      surgery was ascertained to considerably relieve painful sensations, to permit the
      better capacities of patients' movements. Multifactorial analysis of life quality
      in patients demonstrated the obvious advantages of reparative mobilizing
      operations on the joints over arthrodesing ones. A comprehensive evaluation of
      the efficiency of operations should take into account not only the traditional
      objective clinical and X-ray parameters, but also the subjective criteria for the
      quality of life in patients.

PMID- 17195592
TI  - [The specific features of surgical spinal stabilization in children with
      tuberculous spondylitis complicated by severe kyphosis].
AB  - Procedures for anterior spine fusion and posterior instrumental spinal fixation
      have been developed for the surgical treatment of childhood tuberculous
      spondylitis complicated by severe kyphotic deformity. The optimum method of the
      instrumental fixation is the use of multisupport constructions with the
      heterodirectional action of corrective efforts (in 15 children). Anterior
      osteoplastic stabilization of the vertebral column, by applying brace cortical
      grafts with saddle-shaped hollows on the tips of its ventral projection, was
      applied in 6 children. A significant and steady-state correction of kyphosis was
      achieved in all the cases; there were no complications of anterior spine fusion
      and posterior instrumental fixation.

PMID- 17195593
TI  - [Surgical treatment of patients with micro-cystitis of tuberculous and other
      etiology].
AB  - The urinary bladder was reconstructed by using different segments of the
      gastrointestinal tract in 45 patients aged 21 to 72 years. The indication for
      surgery was microcystis of tuberculous and other etiology in 28 (62.2%) and 17
      (37.8%) patients, respectively. The overall post-operative mortality was 2.2% (1
      patient). Early and late complications were observed in 17.8 and 30.4% patients,
      respectively. Analysis of the causes of complications has indicated that they are
      associated with the urine diversion method and with the scope of urinary bladder
      resection. Seven repeated operations were performed. Augmentation cystoplasty
      should follow subtotal microcystectomy. For correction of azotemia and for
      prevention of stricture in the early postoperative period, the neocystis should
      be continuously irrigated with antiseptic solutions in order to eliminate urine,
      mucus, and blood clots.

PMID- 17195594
TI  - [D. G. Kovalenko--the founder of Russian surgery for spondylitis].

PMID- 17195595
TI  - [A. A. Sukonshchikova--the founder of the Leningrad (St. Petersburg) school of
      phthisioophthalmologists].

PMID- 17195596
TI  - [A. E. Garbluz--a surgeon and a manager].

PMID- 17195597
TI  - [Hand involvement in Thevenard's disease: a new "phlegmonous" form. An
      exceptional case report].
AB  - Thevenard's disease is a rare familial ulcero-mutilating acropathology involving
      the peripheral nervous system. It typically begins on the feet and only rarely
      spreads to the hands late in the course of the disease. It first causes cutaneous
      ulcerations and then secondary osseous deformations and osteoarticular
      destruction, due to a distal loss of temperature sensation. We report the case of
      an 87 year old patient who suffered from a particular clinical form, undescribed
      as yet in the literature and characterized by local and general superinfections
      predominately on the hands. We term this the "cellulitic" presentation or form of
      Thevenard's disease.

PMID- 17195598
TI  - [Scapho-trapezio-trapezoidal arthrodesis for scapho-trapezio-trapezoidal
      osteoarthritis].
AB  - Scapho-trapezio-trapezoid arthrodesis was originally performed for the treatment
      of scapho-lunate instability. However, only a few publications have described
      this technique for treatment of osteoarthritis of the scapho-trapezio-trapezoid
      (STT) joint. The purpose of this paper is to analyze the results of triscaphoid
      arthrodesis for STT osteoarthritis with a long-term follow-up. Thirteen cases of
      osteoarthritis of the STT joint in twelve patients, all treated by STT
      arthrodesis, were reviewed with an average follow-up of 60 months. Pain was
      classified according to Alnot's classification: eight patients were classified as
      grade III, two as grade IV and two as grade II. The average preoperative range of
      motion of the wrist was 51 degrees for flexion, 39 degrees for extension, 9
      degrees for radial deviation and 28 degrees for ulnar deviation. Grip strength
      was compared to the contralateral side. Radiographic changes were classified
      according to Crosby's classification, including sublevels for carpal instability.
      Four wrists were classified 2a and nine wrists were classified 2b. The average
      radio-lunate and scapho-lunate angles were 14 and 45 degrees respectively. Pain
      was improved in all patients (P = 0.05) all of whom were subjectively satisfied.
      Strength and range-of-motion did not statistically decrease after STT arthrodesis
      except for wrist extension (P = 0.03). Radio-lunate and scapho-lunate angles were
      unchanged in five patients and improved in five patients. There were four non
      unions of whom two patients without pain were not re-operated. The other two were
      re-operated with the same technique leading to fusion. Scapho-trapezio-trapezoid
      arthrodesis is an efficient procedure for STT osteoarthritis with regard to pain
      reduction. Strength and global range-of-motion are not modified by this
      procedure. Moreover, as it limits carpal instability, this procedure is
      preferable in active patients.

PMID- 17195599
TI  - [The trapezio-metacarpal joint: the strain of the ligaments as a function of the
      thumb position. Study on an enlarged model].
AB  - INTRODUCTION: The aim of this paper was to develop an enlarged anatomical model
      of the trapezio-metacarpal joint in order to measure the strains on the ligaments
      when this joint was passively moved in several directions under constant loading.
      MATERIAL AND METHOD: A model of the two first rays of the hand was made in
      polystyrene, at a X3 enlargement, and the ligaments substituted by rubber bands
      with well characterized mechanical properties so as to reproduce the actual ratio
      of stiffness (approximately = 10) of the different tissues (bones and ligaments)
      found in real life. The first metacarpal was moved in 6 directions as described
      by Ebskov (1970) and Pieron (1973, 1980) using a small spring exerting a constant
      force (1.5 N) tilted at 30 degrees with respect to the transverse plane. The
      strain was measured between two white marks for each model ligament and each
      direction respectively, and the percentage of lengthening was calculated. A
      statistical study was performed using the non-parametrical Test of Wilcoxon in
      order to compare the ligament strains obtained in the different directions of
      loading. RESULTS: The largest strains were observed in the intermetacarpal
      ligament and in the anterior oblique ligament reaching 26 to 39% in direction J
      (posteromedial) and in direction L (posterolateral). Deformations of the two
      parts of the dorsoradial ligament and of the posterior oblique ligament were
      equal or inferior to 12% and were observed in the other 4 directions: D, F, K, I
      (Anterolateral, maximal anteposition, anteromedial, medial) and their
      combinations. CONCLUSION: . These data may be useful for helping the
      understanding of the biomechanics of the basal joint of the thumb. Nevertheless,
      we are dealing here with a simplified model, which must be considered with
      caution if the results are to be applied to the living joint.

PMID- 17195600
TI  - Psychotherapy research at the start of the 21st century: the persistence of the
      art versus science controversy.
AB  - This article offers an overview of prominent general trends in the field of
      psychotherapy research. We consider 3 areas of the literature: metaanalytic
      reviews addressing the effectiveness of psychotherapy, the movement to identify
      empirically supported treatments (EST), and research on the "common factor" or
      "contextual" models of psychotherapy. We present narrative reviews of selected
      literature associated with each area. The reviews highlight several issues
      currently confronting the field. Metaanalytic reviews underscore 2 conclusions:
      psychotherapy is superior to the absence of treatment, and different approaches
      to psychotherapy yield equivalent effects. In counterpoint to these findings, the
      EST movement emphasizes the empirical demonstration that specific psychotherapies
      have efficacy for specific disorders. Misinterpretation of EST findings has led
      to considerable controversy. Although EST research can identify causal effects of
      therapy, it has less capacity to explain how these effects come about. We suggest
      an appropriate perspective on EST findings. Considerable evidence supports the
      importance of common factors as mechanisms of change; at present, however, this
      evidence is predominantly correlational. We conclude that a blending of EST
      studies and research on the common factors represents the greatest potential for
      advancing the field. Studies to identify specific ESTs are key to validating the
      efficacy of psychotherapy approaches and need to be undertaken with the
      psychodynamic and experiential therapies. Greater emphasis on common factors in
      research, training, and practice can advance understanding about change processes
      in efficacious therapies, facilitate the development of sensitive clinicians, and
      increase the effectiveness of mental health services.

PMID- 17195601
TI  - The value of neuroscience strategies to accelerate progress in psychological
      treatment research.
AB  - Major findings from the past 55 years of psychological treatment research
      indicate that 3 questions are now pivotal to continued practice-relevant
      progress: What is the nature of the problem(s) to be treated? What are the causal
      change mechanisms of efficacious psychological treatments? Can more efficient and
      broadly effective psychological treatments be developed? Contemporary cognitive,
      affective, and behavioural neurosciences offer particularly promising resources
      for psychological treatment research that can help accelerate progress regarding
      these questions. This article explains why the questions are pivotal and presents
      neuroscience findings to illustrate how progress can be made on each one and for
      diverse problems and disorders such as major depression, posttraumatic stress
      disorder, obsessive-compulsive disorder, drug addiction, and regulation of
      negative affect.

PMID- 17195602
TI  - What clinical and symptom features and comorbid disorders characterize
      outpatients with anxious major depressive disorder: a replication and extension.
AB  - OBJECTIVE: We previously found that 46% of the first 1450 outpatients with
      depression participating in the multicentre Sequenced Treatment Alternatives to
      Relieve Depression (STAR*D) project qualified for the designation of anxious
      depression. This study was designed to replicate and extend our initial findings
      in a subsequent, larger cohort of outpatient STAR*D participants with
      nonpsychotic major depressive disorder (MDD). METHODS: Baseline clinical and
      sociodemographic data were collected on 2337 consecutive STAR*D participants. A
      baseline 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor
      score of 7 or higher was designated as anxious depression. We identified
      concurrent Axis I disorders with the Psychiatric Diagnostic Screening
      Questionnaire (PDSQ), using a 90% specificity threshold. Depressive symptoms were
      assessed by clinical telephone interview with the 30-item Inventory of Depressive
      Symptomatology-Clinician-Rated (IDS-C30). RESULTS: The prevalence of anxious
      depression in this population was 45.1%. Patients with anxious MDD were
      significantly more likely to be in primary care settings and to be women,
      nonsingle, unemployed, Hispanic, less educated, and suffering from severe
      depression, both before and after adjustment for overall depression severity.
      Patients with anxious depression were significantly more likely to meet PDSQ
      thresholds for generalized anxiety disorder, panic disorder, obsessive-compulsive
      disorder, posttraumatic stress disorder, agoraphobia, hypochondriasis, and
      somatoform disorder, both before and after adjusting for baseline depression
      severity. Individuals with anxious depression were also significantly less likely
      to endorse IDS-C30 items concerning atypical features and were significantly more
      likely to endorse items concerning melancholic-endogenous depression features,
      both before and after adjusting for baseline depression severity. CONCLUSIONS:
      This study clearly replicates our previous STAR*D findings and supports the
      notion that anxious depression may be a valid diagnostic subtype of MDD, with
      distinct psychiatric comorbidities and clinical and sociodemographic features.

PMID- 17195604
TI  - The incidence of methylphenidate use by Canadian children: what is the impact of
      socioeconomic status and urban or rural residence?
AB  - OBJECTIVE: To examine socioeconomic, demographic, and behavioural factors that
      influence the incidence of methylphenidate use among children aged 4 to 13 years.
      METHOD: A total of 11,316 children, aged 2 through 11 years, from Cycle 1 (1994
      95) of the National Longitudinal Survey of Children and Youth were followed up 2
      years later in Cycle 2 (1996-97). The outcome measure was methylphenidate use in
      Cycle 2. Individual-level explanatory variables included sex, age, socioeconomic
      status (SES), mother's age at birth of child, lone-parent family status, parental
      working status, and hyperactivity-impulsivity and inattention probabilities. Area
      level explanatory variables included income and rural or urban residence. We used
      hierarchical linear modelling to examine individual- and area-level factors that
      predicted methylphenidate use. RESULTS: The strongest predictors of
      methylphenidate use were behavioural: children with high hyperactive-impulsive
      and (or) inattention behaviours in 1994, compared with children low on these
      behaviours, were 4.5 to 6 times more likely to use methylphenidate 2 years later.
      SES remained a significant predictor of the incidence of methylphenidate use,
      even when other significant predictors were held constant, with lower SES being
      associated with higher use. Area-level income also predicted methylphenidate use.
      CONCLUSION: Even when children with similar behavioural symptoms and demographic
      characteristics were compared, socioeconomic factors had a significant impact on
      incidence of methylphenidate use.

PMID- 17195603
TI  - Canadian psychiatrists' current attitudes, practices, and knowledge regarding
      fitness to drive in individuals with mental illness: a cross-Canada survey.
AB  - OBJECTIVES: To assess current attitudes, practices, and knowledge of Canadian
      psychiatrists regarding fitness to drive in individuals with mental illness and
      to explore variations according to provincial legislation. METHOD: We carried out
      a national cross-sectional survey, using a random sample of psychiatrists. We
      used a mail survey to collect data. RESULTS: In total, 248 psychiatrists
      participated; the response rate was 54.2% on traced subjects. The majority
      (64.1%) reported that they strongly agreed or agreed that addressing patients'
      fitness to drive is an important issue. However, only 18.0% of respondents were
      always aware of whether their patients were active drivers. One-fourth strongly
      agreed or agreed that they were confident in their ability to evaluate fitness to
      drive. In discretionary provinces, 29.3% of psychiatrists reported not knowing
      their provincial legislation, as did 14.6% of psychiatrists in mandatory
      provinces; of those responding, 54.0% from discretionary provinces and 2.8% from
      mandatory provinces gave incorrect answers. DISCUSSION: Psychiatrists' responses
      demonstrate a broad range of attitudes, practices, and knowledge. There appears
      to be a large gap between what is expected of psychiatrists and their readiness
      and self-perceived ability to make informed clinical decisions related to driving
      safety. CONCLUSION: There is a clear need for education and guidelines to assist
      psychiatrists in decision making about driving fitness.

PMID- 17195605
TI  - [Birth order, behavioural problems, and the mother-child relationship in siblings
      aged 4 to 11 years from a 2-child family].
AB  - Birth Order, Behavioural Problems, and the Mother-Child Relationship in Siblings
      Aged 4 to 11 Years From a 2-Child Family OBJECTIVE: This study was designed to
      define the relation between some sibling characteristics (birth order, sex, and
      interval between successive births) and some behavioral problems in children, on
      the one hand, and certain dimensions of the mother-child relationship, on the
      other hand. METHOD: The sample, from National Longitudinal Survey of Children and
      Youth, included 1,196 families with 2 biological children aged 4 to 11 years.
      Behavioural problems and dimensions of the mother-child relationship were
      assessed by mothers. Repeated-measures multivariate analyses of variance were
      conducted. RESULTS: Analyses showed that first-born children have more
      internalized symptoms than second-born children. Second-born children also have
      more positive interactions with their mothers than first-born children. The
      interval between successive births does not affect these results. CONCLUSION:
      Several differences emerged between siblings. Health professionals should take
      these findings into account in their clinical assessments.

PMID- 17195606
TI  - [Biology of cardiac and vascular senescence].
AB  - None of the many theories of senescence can account for the aging process in its
      entirety. These theories include the evolutionary theory of aging and its EvoDevo
      corollary, the replicative senescence and free radicals theory, theories based on
      large-scale analyses (proteomics, etc.), and systemic theories. Cardiovascular
      senescence is first and foremost due to vascular senescence. Aging is associated
      with enhanced aortic characteristic impedance, which is mainly due to glycation
      of vessel wall proteins. This increased impedance overloads the left ventricle
      and causes compensatory left ventricular hypertrophy, usually associated with
      fibrosis. Extreme aging (> 80 years in humans, > 30 months in rats) is associated
      with age-related heart failure. Senescence favors heart failure, atrial
      fibrillation and cardiac hypertrophy. It is also associated with increased
      systolic pressure and decreased diastolic pressure. The most characteristic
      features are enhanced pulse pressure and arterial compliance.

PMID- 17195607
TI  - [Hypertension in the elderly].
AB  - Systolic blood pressure rises with age, and the prevalence of hypertension
      (systolic pressure of 140 mmHg or more and diastolic pressure below 90 mmHg)
      exceeds 70% after the age of 70. At any age, high systolic pressure is associated
      with an increased risk of cardiovascular death, stroke and myocardial infarction.
      Antihypertensive drugs reduce cardiovascular mortality and morbidity in patients
      with systolic pressure exceeding 160 mmHg. The ability of blood pressure
      reduction to prevent cardiovascular events in elderly hypertensive patients is
      often compromised by poor systolic pressure control. This is due to the
      relatively limited efficacy of antihypertensive medications to normalize systolic
      blood pressure, but also to the fact that many physicians fail to follow systolic
      hypertension treatment guidelines.

PMID- 17195608
TI  - [Coronary syndromes in the elderly].
AB  - Acute coronary syndromes (ACS) are frequent in the elderly and carry a poor
      prognosis. Severe coronary artery disease, frequent comorbidity, late diagnosis,
      and treatments themselves are responsible for high morbidity and mortality rates.
      Reluctance to treat elderly patients with new mechanical or chemical
      revascularization techniques is due to the higher risk profile. ACS may or may
      not be accompanied by ST elevation: STEMI corresponds to acute myocardial
      infarction before myocardial necrosis, while non STEMI corresponds to unstable
      angina and subendocardial necrosis. Despite the high incidence of STEMI in the
      elderly, older patients have been excluded from large randomized trials. Chemical
      and mechanical reperfusion are the two recommended treatments for patients
      hospitalized before the 6th hour. Intravenous thrombolysis is the most common
      strategy: it offers a 26% reduction in mortality compared to conventional
      treatment, but carries a higher risk of brain hemorrhage than in younger
      patients. In high-throughput centers with experienced cardiologists, primary
      angioplasty seems to be the optimal strategy, with fewer deaths and recurrent
      ischemia. Two approaches are possible for NST-ACS: conservative or
      interventional. The latter includes medical treatment, early coronarography and
      revascularization by angioplasty or surgery. This strategy, combined with
      aspirin, clopidogrel, and glycoprotein II B/IIIa receptor inhibitors, offers a
      larger absolute reduction in the 30-day major adverse clinical event rate than
      conservative management. Dedicated randomized trials are needed to provide a more
      thorough picture of ACS management in the elderly.

PMID- 17195609
TI  - [Management of heart failure in the elderly patient].
AB  - The prevalence of heart failure increases exponentially in the elderly
      population, particularly in western countries. Heart failure is associated with
      multiple and lengthy hospital stays and carries a high mortality rate. The
      authors analyzed management modalities of 2780 octogenarians enrolled in the 11
      000-patient cohort of the Euro Heart Failure Survey I study. The patients were
      admitted for suspected or confirmed heart failure to 115 hospitals in 24
      countries belonging to the European Society of Cardiology. The results show that
      diagnostic investigations and treatment modalities do not comply with
      international guidelines. The in-hospital and 12-week mortality rates were high.

PMID- 17195610
TI  - [Cardiac arrhythmias in the elderly].
AB  - In the elderly, cardiac arrhythmias and conduction disturbances are characterized
      by their high frequency, diagnostic difficulties, low tolerance, and delicate
      treatment. Atrial fibrillation, the prevalence of which exceeds 10% after 80
      years, is usually related to hypertensive or ischemic heart disease, and is the
      cause or the consequence of heart failure. It is first and foremost a cause of
      thromboembolic events, and especially cerebrovascular embolism. In elderly
      patients, sinus node dysfunction and AV block are often induced or aggravated by
      drugs. The iatrogenic risk associated with antiarrhythmic drugs (especially class
      I) and antithrombotic drugs is elevated in the elderly, and these agents must
      thus be used with great care. Ventricular rate control is often a safer option
      than sinus rhythm control for atrial fibrillation. Ablative methods and cardiac
      pacing techniques are other therapeutic options.

PMID- 17195611
TI  - [Pharmacokinetics of cardiovascular drugs in the elderly].
AB  - Adverse drug effects are more frequent in elderly patients, especially with drugs
      that have small safety margins. This is the case of many cardiovascular drugs.
      Patients who are frail, owing to their age and their psychomotor, nutritional and
      social stratus, are particularly at risk. Two pharmacokinetic factors appear to
      be of major concern, namely the age-related decrease renal function and changes
      in drug metabolism and distribution. Renal function is probably the single factor
      most responsible for altered drug levels in the elderly. The normal age-related
      decrease in creatinine clearance can lead to the accumulation of drugs that are
      normally excreted by the kidneys without being inactivated Dose adjustment of
      such drugs is usually based on the Cockcroft-Gault formula of creatinine
      clearance. Changes in hepatic metabolism and drug distribution are less commonly
      taken into account. The avoidance of drug toxicity requires familiarity with the
      medications prescribed and particular vigilance for signs of adverse effects.

PMID- 17195613
TI  - [Association of lung function decline with the microsatellite polymorphism in the
      heme oxygenase-1 gene promoter, in a general population sample. Results from the
      Longitudinal European Community Respiratory Health Survey (ECRHS-France)].
AB  - Heme oxygenase (HO1) acts against oxidants which are thought to play a major role
      in the pathogenesis of chronic obstructive pulmonary disease (COPD). A (GT)n
      repeat polymorphism in the HO1 gene promoter can modulate the transcription of
      this gene in response to oxidative stress. We postulated that this polymorphism
      might be associated with the degree and decline of lung function in subjects
      exposed to oxidative stress (smokers). We genotyped 749 French subjects (20-44
      years, 50% men, 40% never-smokers) who were examined in both 1992 and 2000 as
      part of the ECRHS. Lung function was assessed by measuring FEV1 (Forced
      Expiratory Volume in 1 second) and the FEV1/FVC (Forced Ventilatory Capacity)
      ratio. We compared long (L)-allele carriers ((GT)n > or = 33 repeats for one or
      two alleles) to non-carriers. During the 8-year study period, the mean annual
      FEV1 and FEV1/FVC declines were -30.9 +/- 31.1 ml/year and -1.8 +/- 6.1
      units/year, respectively. The FEV1/FVC decline was steeper in L-allele carriers
      than in non-carriers (-2.6 +/- 5.5 vs -1.5 +/- 6.4, p = 0.07). There was a strong
      interaction between allele L and smoking. In 2000, allele L was associated with
      lower FEV1 and FEV1/FVC values in heavy smokers (J20 cig/day) only (p for the
      interactions, 0.07 and 0.002 respectively). Baseline heavy smokers carrying
      allele L showed the steepest FEV1 decline (-62.0 +/- 29.5 ml/year) and the
      steepest FEV1/FVC decline (-8.8 +/- 5.4 units/year) (p for the interactions,
      0.009 and 0.0006). These results suggest that a long (L) HO1 gene promoter
      increases the risk of airway obstruction in heavy smokers.

PMID- 17195612
TI  - [Cardiac surgery in the elderly].
AB  - Cardiac disease in the elderly represents a major burden on public healthcare.
      Their frequences is linked to ageing process of general population and prevalence
      of cardiovascular diseases in older ages. Two diseases are of primary importance
      in elderly: Aortic valve stenosis is the most common. Valve replacement is the
      procedure of choice in the majority of patients. In coronary artery disease,
      although drug eluting stents have improved the results of percutaneous coronary
      intervention, coronary artery bypass grafts have still has an important place in
      the treatment of severe lesions: multivessel disease, left main and diabetes. Our
      report is a retrospective review of 8871 patients aged 70 years or more operated
      on between 1974 and 2004.

PMID- 17195614
TI  - [Quantification of pharmacological progress by the French National Health
      Authorities].
AB  - The French National Health Authority has delegated to the Transparency Commission
      (TC) responsibility for defining and quantifying therapeutic progress and for
      certifying the therapeutic added value of new drugs. It is essential to
      distinguish between pharmacologic innovation and therapeutic progress. The TC
      considers that a new product offers therapeutic progress if it: 1) improves
      patient management, 2) represents a significant clinical breakthrough, and/or 3)
      meets a previously uncovered need. Therapeutic progress must be supported by
      quantitative or qualitative clinical evidence of improved therapeutic tolerance,
      compliance or maintenance. The TC measures progress in terms of the enhancement
      of therapeutic value (ETV) relative to existing products. Ideally, ETV should be
      evaluated in head-to-head comparisons, but companies often prefer placebo
      controlled studies, meaning that indirect comparisons are unavoidable. ETV is
      graded in five levels, ranging from I (major progress) to V (no progress), and is
      attributed for a specific target population. The ETV only measures expected
      therapeutic progress, to be confirmed in post-registration studies. TC decisions
      are taken into account by the commission that determines drug prices. One pending
      economic issue involves "me-too" products. Indeed, scientific committees cannot
      be expected to regulate market competition--for example, to decide when to inform
      decision-makers that the number of statins or betablockers on the market is
      sufficient to cover requirements. Another delicate problem concerns efforts by
      brand-name drug companies to circumvent generic drugs, notably by introducing
      fixed-dose combinations. Although the assessment of therapeutic progress is based
      on objective, verifiable and reproducible criteria, it can only be carried out
      fairly within a collaborative framework independent of pharmaceutical companies,
      healthcare insurers and consumer associations.

PMID- 17195615
TI  - [The worrying rise in the frequency of cesarean section].
AB  - The rise in the incidence of Cesarean section over the last thirty years is due
      to several factors. In particular, maternal age is increasing, parity is
      declining, and situations potentially requiring Cesarean section are more
      frequently encountered than before (prematurity, medically assisted procreation,
      antenatal diagnosis, previous Cesarean section, etc.). Medicolegal pressure is
      also increasing, and the precautionary principle is leading more and more
      physicians to propose Cesarean section rather than trial labor. However, although
      the risks of this form of delivery have decreased, they are still higher than
      those of vaginal delivery, except in the emergency setting. Moreover, various
      pathophysiologic studies have demonstrated marked changes in the elevator
      muscles, nerves and pelvic support after vaginal delivery. The maternal morbidity
      and mortality of elective caesarean delivery at term, before the onset of labor,
      appear to be similar to those associated with vaginal birth. However, the
      maternal risks (particularly placenta praevia, placenta accreta, and uterine
      rupture) during subsequent pregnancies following Cesarean delivery require
      careful evaluation. After Cesarean section, the risk of placenta praevia during
      the next pregnancy is between 1% and 4%. There is subsequently a linear increase,
      with the risk of placenta praevia reaching nearly 10% after four Cesarean
      deliveries. The risks and benefits of each form of delivery are extremely
      difficult to weigh up, and predictors of safe vaginal delivery are lacking.

PMID- 17195616
TI  - [Surgical treatment of otosclerosis].
AB  - A significant step forward in otosclerosis surgery was made in 1956 with the
      advent of stapedectomy. This led to a significant reduction in surgical
      complications and to a high level of patient satisfaction. Hearing aids are the
      alternative to surgery, and have themselves undergone considerable technical
      improvements. In advanced otosclerosis, cochlear implants can improve hearing
      when stapes surgery and a conventional hearing aid are inadequate. These advances
      are modifying the surgical indications.

PMID- 17195617
TI  - [Angiotensin and EGF receptor cross-talk in chronic kidney diseases: towards a
      new therapeutic approach].
AB  - Angiotensin plays a major role in renal deterioration, and inhibition of the
      renin-angiotensin system slows the progression of renal lesions after nephron
      reduction both in animal models and in humans with chronic kidney diseases. The
      EGF receptor (EGFR) has recently been recognized as a key molecule in the
      progression of chronic renal failure, but the interaction between angiotensin and
      EGF is poorly understood. We show that transgenic mice harboring a dominant
      negative form of EGFR are resistant to the progression of renal lesions induced
      by nephron reduction or angiotensin infusion. TGF-alpha, an EGFR ligand, and its
      sheddase TACE, are overexpressed after angiotensin infusion, and angiotensin
      induced renal lesions are blunted in TGF-alpha knockout mice and by
      pharmacological TACE blockade. After nephron reduction, angiotensin-converting
      enzyme inhibitors and angiotensin receptor antagonists prevent TGF-alpha and TACE
      accumulation. These results indicate that EGFR transactivation by angiotensin
      plays a crucial role in renal deterioration and that pharmacological inhibitors
      of TACE might be useful for preventing the progression of chronic kidney
      diseases.

PMID- 17195618
TI  - [Drug binding to blood proteins: characteristics, roles and pathophysiological
      changes].
AB  - HSA and AGP are the only plasma proteins capable of binding drugs through
      specific sites with high affinity. As such, they can limit drug distribution and,
      sometimes, drug elimination. Such binding is called restrictive. Low binding
      capacities are said to be permissive, as they do not lead to drug retention.
      Modifications of restrictive binding can influence other pharmacokinetic
      parameters and also have clinical implications.

PMID- 17195619
TI  - [Epidemiological aspects of Helicobacter pylori infection].
AB  - Helicobacter pylori is thought to infect about half the world's population. The
      prevalence of H. pylori infection varies widely by geographic area, age,
      ethnicity and socioeconomic status. Rates appear to be higher in developing
      countries, where most infections occur during childhood. Inadequate sanitation,
      low socioeconomic status and overcrowding seem to be related to a higher
      prevalence of H. pylori infection. No predominant route of transmission has been
      identified, and possibilities include the fecal-oral, oro-oral and gastro-oral
      routes. Recent studies show that H. pylori strains expressing the biologically
      active CagA protein are more closely associated with stomach cancer.

PMID- 17195620
TI  - [H5N1: vaccine solutions for humans and other animals].
AB  - The hypervirulence of H5N1 influenza virus makes it impossible to produce a
      vaccine traditionally (with egg embryos), but there are alternative solutions. A
      live recombinant fowl-pox H5 virus is used for avian pathology. An inactivated
      H5N2 adjuvant vaccine is rendered immunogenic by using hemagglutinin H5 (DIVA
      technique). Disease prevention strategies differ between European and Asian
      countries. WHO has opted for a recombinant vaccine based on a non pathogenic
      virus (PR8) to which modified H5 and N1 from a pandemic virus are grafted The
      poor immunogenicity of this vaccine will require the use of large doses and
      immunostimulants. A live vaccine based on an adenovirus coupled to the H5 gene
      was recently developed. Finally, Chinese authors are examining the preventive and
      curative potential of hyperimmune serum raised in animals.

PMID- 17195621
TI  - [Autochthonous hepatitis E in France].
AB  - Hepatitis E must no longer be considered simply as an exotic disease occasionally
      imported from developing countries. Autochthonous hepatitis E exists in France.
      In spite of certain difficulties and limits, biological markers of hepatitis E
      have to be included in algorithms for etiological diagnosis of acute hepatitis,
      even if the patient has not recently traveled abroad. Based on a recombinant
      protein of the viral capsid, more sensitive serological assays should soon be
      available. The potential severity of hepatitis E, especially during pregnancy,
      calls for a national surveillance program, including evaluation of the animal
      reservoir and the risk associated with drinking water and food.

PMID- 17195622
TI  - [Treatment of ankylosing spondylitis with anti-TNFalpha agents].
AB  - Non steroidal antiinflammatory drugs (NSAID) used to be the only drugs active in
      ankylosing spondylarthritis (AS). However, they are inadequate or ill-tolerated
      in many patients, and have no proven impact on disease-related structural
      changes. Clinical trials have recently shown the impressive efficacy of two anti
      TNFalpha agents (infliximab and etanercept) in patients with NSAID-resistant SA.
      These drugs attenuate inflammatory pain, stiffness and functional disability, and
      improve mobility and quality of life. Tolerability is satisfactory, and efficacy
      persists during several years of treatment. Moreover, these agents induce
      regression of acute inflammatory lesions, as demonstrated by magnetic resonance
      imaging (MRI). A 2-year X-ray study indicates that they also slow the progression
      of structural lesions. More studies are needed to determine the precise place of
      anti-TNFalpha agents in this setting.

PMID- 17195624
TI  - [Surgical treatment of blepharospasm: results of a study of 138 patients using an
      improved disability scale].
AB  - We applied a new blepharospasm clinical disability scale to the evaluation of
      blepharospasm surgery in a group of 138 patients. This scale analyzes six
      parameters of daily life, namely reading, watching television, household tasks,
      walking, employment, and driving. The patients had either essential blepharospasm
      or pretarsal dystonia. Frontalis suspension of the eyelid gave slightly better
      functional results than orbicularis resection in some patient subgroups.

PMID- 17195623
TI  - [Contribution of sacroiliac magnetic resonance imaging (MRI) to the evaluation of
      infliximab efficacy in spondyloarthropathy (a prospective study of 34 patients)].
AB  - Thirty-four patients who met ESSG criteria for spondylarthropathy and were
      eligible for anti-TNFalpha treatment (infliximab) were enrolled in this open
      label study lasting 14 weeks. The aims were to evaluate the progression of
      sacroiliitis by means of MRI, and to determine the positive predictive value of
      this exam for the treatment response. Patients underwent MRI of the sacroiliac
      region at baseline (W0), and also at 14 weeks if the baseline MRI showed
      sacroiliitis. Two blinded readers reviewed all imaging studies. The patients also
      had a physical examination and ESR and CRP assays at W0 and W14. Sacroiliitis was
      found in 22 patients (65%) at W0, but only 18 of these patients had a second MRI
      at W14, for technical reasons. After 14 weeks of therapy, MRI signs of sacroiliac
      inflammation diminished by 77.7% on average. Clinical and biological parameters
      also improved. However, MRI was not predictive of the treatment response.
      Sacroiliac MRI seems to be interesting for objective therapeutic evaluation and
      monitoring of patients with spondyloarthropathy.

PMID- 17195625
TI  - [Evolution of the vaccination timetable in Morocco].
AB  - Morocco has always been aware of the importance of vaccination and has been
      implementing an ambitious vaccination policy for several decades. The first
      vaccination campaigns started in the sixties. The Extended Vaccination Program
      (EVP) was launched in 1981 and restructured six years later, being renamed the
      National Immunization Program (NIP). Regular follow-up of vaccine efficacy has
      led to several changes in the national vaccination timetable, including new
      antigens and boosters. Protection against tuberculosis, diphtheria, tetanus,
      whooping cough, poliomyelitis, etc. has considerably improved in Morocco.
      Neonatal tetanus and diphtheria have been eliminated, along with poliomyelitis
      (certified by WHO in 2001). Future efforts will focus on reducing urban-rural
      disparities, and on implementing the WHO program for eliminating measles and
      congenital rubella.

PMID- 17195626
TI  - [Evaluation of residual immune response against human pox virus before and after
      revaccination in healthy volunteers].
AB  - Although the risk of smallpox virus being used as a terrorist weapon is very low,
      it is mandatory to examine potential vaccination strategies, and also the
      residual immunization rate in the general population. During revaccination of a
      national intervention team, the residual immunity of 184 volunteers was
      determined by assaying T memory cells in the gamma interferon ELISpot test, and
      central T memory cell responses in a proliferation assay. Three-quarters of the
      subjects had a proliferative response. This response was lower after the age of
      55 years but could be reactivated by revaccination.

PMID- 17195627
TI  - [The Antonine plague].
AB  - During the reign of Marcus Aurelius, the Roman Empire was struck by a long and
      destructive epidemic. It began in Mesopotamia in late AD 165 or early AD 166
      during Verus' Parthian campaign, and quickly spread to Rome. It lasted at least
      until the death of Marcus Aurelius in AD 180 and likely into the early part of
      Commodus' reign. Its victims were "innumerable". Galen had first-hand knowledge
      of the disease. He was in Rome when the plague reached the city in AD 166. He was
      also present during an outbreak among troops stationed at Aquileia during the
      winter of AD 168-169. His references to the plague are scattered and brief but
      enough information is available to firmly identify the plague as smallpox. His
      description of the exanthema is fairly typical of the smallpox rash, particularly
      in the hemorrhagic phase of the disease.

PMID- 17195628
TI  - [Methodological features of magnetic resonance imaging mammography].
AB  - By studying 211 females by currently available radiation techniques, such as X
      ray study, ultrasonography, and magnetic resonance imaging mammography (MRIM),
      the authors consider that the specificity of contrast-enhanced MRIM (CE MRIM) is
      greater than that of MRIM without administering magnetic resonance contrast
      agents (MRCA). CE MRIM reveals clinically suspicious early-stage breast lesions
      and defines the stage of a tumorous process, the patients being unexposed to
      ionizing irradiation. CE MRIM as an auxiliary technique becomes one of the most
      informative ones, particularly in girls, early reproductive-age females with
      developed glandular tissue, and pregnant females. In the authors' opinion, the
      total algorithm of a breast study in this group of patients in specialized
      medical centers where trained physicians work should differ from the generally
      accepted algorithm: instead of applying X-ray mammography (XRM) as a basic method
      of primary diagnosis, ultrasound mammography using Doppler color mapping,
      followed by MRIM or XRM should be employed.

PMID- 17195629
TI  - [Human cerebellar dimensions as evidenced by magnetic resonance imaging].
AB  - Magnetic resonance imaging data were analyzed in 340 patients (224 males, 116
      females) aged 20 to 80 years. The dimensions of cerebellum were estimated on its
      standards sections. A relationship was found between the cross dimension of the
      cerebellum and the craniometric indices. The cerebellar dimensions in males were
      greater than those in females. Decreased cerebellar dimensions were observed in
      subjects over 60 years of age.

PMID- 17195630
TI  - [Pulmonary scintigraphy in evaluating the efficiency of surfactant therapy in the
      complex treatment of patients with destructive pulmonary tuberculosis].
AB  - Functional impairments of the mucociliary system (MCS) are known to develop in
      destructive tuberculous inflammation in the lung tissue. The effect of surfactant
      agents and their production stimulants is to recover the ventilation and gas
      exchange functions of the lung. The radioaerosol technique that adequately
      characterizes the deposition of an inhaled agent in the bronchial tree and
      records the state of mucociliary clearance (MCC) and MCS in different portions of
      the lung by the rate of tracer washout is of the greatest information value for
      the evaluation of MCC in vivo. Its normal values are in rather wide ranges so the
      absolute values are of low informative value. By taking into account the
      variability in the tracer washout range in health, the authors used only the time
      course of relative changes in this parameter--before and after surfactant
      therapy. The capacities of pulmonary scintigraphy were employed to monitor the
      efficiency of treatment for tuberculosis. The percentage of the activities in the
      areas of the right and left lung individually and in combination was estimated,
      by constructing the tracer washout curve. The percentage of 60-minute tracer
      washout was borne in mind to determine the rate of MCC.

PMID- 17195631
TI  - [Potentialities of new radiation technologies (ultrasonography, computed
      tomography, magnetic resonance imaging) in the diagnosis of endocrine diseases].
AB  - In the paper providing the data available in the literature and many years'
      experience gained by the Department of the Moscow Regional Clinical Research
      Institute, the authors describe the potentialities of the currently available
      radiation techniques in the diagnosis of surgical endocrine diseases. The
      incidence of various organ dysfunctions is presented. The authors also consider
      the introscopic symptoms of various endocrinopathies and outline the common
      specific features of the ultrasound, computed tomographic, and magnetic resonance
      imaging pattern of individual masses (including adipose tissue cysts and tumors).
      Emphasis is laid on the leading role of ultrasonography (USG) in the diagnosis of
      thyroid and parathyroid diseases and on the priorities of computed tomography
      (CT) and magnetic resonance imaging (MRI) in visualIzing the abnormal thymus,
      mediastinally ectopic glands, and pituitary tumors. The capacities of each
      technique in the diagnosis of endocrine space lesions of the pancreas and
      adrenals are defined. The increase in the frequency of endocrine abnormalities
      accidentally identified at USG, CT, and MRI, which is noted in the paper, fosters
      the development of new trends in endocrinology and points to the need for
      screening surveys (particularly patients who live in poor environmental areas).

PMID- 17195632
TI  - [Computed tomography in the diagnosis of soft tissue changes in patients with
      chronic osteomyelitis of the femur].
AB  - Computed tomography was used to study soft tissues of the femur in 78 patients
      with its chronic recurrent osteomyelitis and the studied parameters were
      estimated. The fibrous changes were found to be more pronounced in posttraumatic
      osteomyelitis; the thickening of the subcutaneous fat and its atrophy were
      equally marked; the density gradients between the intact muscle, infiltrated
      muscle tissue, and purulent leakage were calculated.

PMID- 17195633
TI  - [Renal angiography and tactics of urological surgical interventions].
AB  - Despite notable advances of the currently available medical imaging techniques:
      Doppler study, nuclear magnetic resonance, X-ray tomography with the construction
      of three-dimensional images, angiography occupies a prominent place in the
      diagnosis of abnormal kidneys, in the endovascular correction of their vascular
      bed, and in the determination of indications for a forthcoming surgical
      intervention, its tactics and scope. According to the authors' data, more than
      half the diagnostic angiogaphic studies have changed the general view of a
      pathological process and affected a further treatment policy. The present paper
      pools the experience accumulated by the Department of X-ray Study and
      Angiography, Research Institute of Urology, Russian Ministry of Health, and
      Moscow City Hospital No. 47 and is intended for wide audience of
      roentgenologists, urologists, and surgeons.

PMID- 17195634
TI  - [Ultrasonography and magnetic resonance imaging in diagnosing recurrent and
      metastatic ovarian cancer].
AB  - The paper deals with the capacities of ultrasonography (USG) and magnetic
      resonance imaging (MRI) in diagnosing recurrent and metastatic ovarian cancer
      along with routine clinical and laboratory studies (physical examination,
      measurement of the tumor-associated serum antigen CA-125) in 95 patients with
      ovarian cancer after primary special treatment. MRI is preferable to USG in
      evaluating the extent of a tumorous process and the invasion of a tumor into the
      adjacent tissues, which is of great value in defining a further treatment policy.

PMID- 17195635
TI  - [Nonionic dimer: safety and effectiveness].

PMID- 17195636
TI  - [Chronic inflammation increases risk of epithelial neoplasia by inducing
      precancerous microenvironment: an evaluation of pathways of disregulation].

PMID- 17195637
TI  - [Frequency of RET/PTC rearrangement and somatic BRAF mutation in papillary
      thyroid cancer].
AB  - Frequency of RET/PTC rearrangement and somatic BRAF mutation was investigated in
      patients with papillary thyroid cancer (PTC) vis-a-vis relevant demographic and
      clinico-pathological features. The study group included 76 patients with a
      female/male ratio of 4.8:1; mean age - 45.7 +/- 9.7 yrs. BRAF mutation was
      identified in 49 (65%) (V600E--47, KSRWS600--1 and E585K--1). RET rearrangement
      was detected in 9 (12%): RET/PTC1--5, RET/PTC3--2, unspecified RET/PTC--1 and
      delta RET/PTC--1. It was age at diagnosis alone that proved to be consistently
      associated with BRAF mutations (p = 0.017). Younger tumor patients were mostly
      prone to RET/PTC rearrangement (p = 0.08). No correlation between mutation and
      clinico-pathological features was established.

PMID- 17195639
TI  - [Impact of photochromotherapy on functional potential of neutrophil granules and
      adaptive status in children with complicated hemangioma].
AB  - Adaptive status was assessed in 50 children. Lysosomal-cationic test was carried
      out in healthy children and 20 patients with complicated hemangioma.
      Photochromotherapy was followed by enhanced functional potential of neutrophil
      granules. That was indicated by greater values of lysosomal-cationic test results
      as well as by higher counts of high-concentration cationic proteins. Elevated non
      specific resistance was accounted for by antistressor reactions.

PMID- 17195638
TI  - [Correlation of hormone-metabolic status in breast cancer and effectiveness of
      adjuvant hormone therapy].
AB  - Hormono-metabolic status was assayed before and after month 6, 12, 24, 36, 48, 54
      and 60 of therapy in 72 patients with receptor-positive tumors of the breast who
      completed 5 years of adjuvant tamoxifen (20 mg/24 hrs) or letrozole (2.5 mg/24
      hrs). Eleven patients were not followed up, 11 relapsed and had metastases while
      50 completed therapy. Significant fall in body mass (Ketle's index), in C-peptide
      concentration after an insignificant rise and C-peptide/insulin ratio 129 min
      after glucose loading, low basal blood level of estradiol as well as stable
      estradiolemia throughout treatment were characteristic of cases of pre-treatment
      recurrence and metastastic spread. Insulin resistance status, basal serum
      estradiol level and fasting its course of development during hormonotherapy
      should be the subject of further research in criteria for adjuvant hormonotherapy
      efficacy.

PMID- 17195640
TI  - [Comparison of blood-serum p53 concentrations in patients with advanced breast
      tumors before and after chemotherapy].
AB  - Investigations of the role of p53 in tumorigenesis and growth, implementation of
      antitumor effect of cytostatics as well as emergence of tumor resistance have
      generally received great emphasis. Since most research was mostly concerned with
      use of tumor tissues, its dynamic aspects were ignored. Our study was concerned
      with p53 assay of blood serum from 10 patients with advanced breast tumors who
      underwent tests before and after a second cycle of chemotherapy. Due to
      immunoblotting technique, p53 was identified in all patients. Its concentration
      varied significantly and was twice as high in some as compared with the others.
      Prior to treatment, distinct differences were recorded in content as well as and
      in the nature of its age-dependent variation after chemotherapy. The highest
      levels were recorded in the age group over 60 yrs. In most patients (5 out of 6)
      under 55, post-treatment concentrations rose, on the average, by 13% while in all
      4 cases of more than 60, they dropped by an average of 18%.

PMID- 17195642
TI  - [Anticarcinogenic action of dietary supplement pheocarpin and its active
      component].
AB  - Anticarcinogenic action of dietary supplement Pheocarpin and its active component
      Natural Coniferous Complex (NCC), in particular, has been studied. Pheocarpin and
      NCC efficiently inhibited tumorigenesis in the mammary gland, large bowel, skin,
      cervix uteri and lungs. Pheocarpin offers considerable advantage as a means of
      reducing the risk of malignant disease.

PMID- 17195641
TI  - [Melatonin inhibits urethane-induced carcinogenesis tumors in murine lung].
AB  - Non-inbred SHR/u 3-month old mice were injected a single dose of urethane 1 g/kg,
      intraperitoneally. Beginning from day I after injection, they received melatonin
      20 mg/l or 2 mg/l with drinking water at nighttime. After 28 days of the
      experiments, mice were sacrificed, lung adenomas counted and examined
      morphologically. Samples of blood and ling tissue were taken from each group and
      assayed for malonic dialdehyde (MDA) and catalase level. Tumor count of lung
      adenomas in the untreated group (control) was 23 +/- 2.63, melatonin 20 mg/l--14
      +/- 1.2 (p < 0.01) and melatonin 2 mg/l--11 +/- 0.72 (p < 0.01). Urethane-treated
      mice revealed increased levels of MDA (62%) and catalase (70.7%) in blood-serum
      and in lung tissue (36.5%) as compared with control. Melatonin treatment
      significantly lowered concentrations of MDA in blood-serum and catalase (blood
      serum and lung) rather than in the lung bearing urethane-induced tumor. Antitumor
      and antioxidant effect of relatively low dosage of melatonin appeared to be more
      effective than those of a larger one.

PMID- 17195644
TI  - [Analysis of failed management of endometrial carcinoma].
AB  - The research included 155 patients with relapsing tumors of the corpus uteri and
      metastases which developed after surgical, combination and multimodality
      treatment. Metastases were found to occur most within the first 12 months of
      follow-up due to faulty staging and inadequate choice of therapy 51%. Tumor
      frequency range was as follows: single--60.6%, multiple tumor--22.6% and
      lymphogenous metastases--16.8%. Vaginal stump involvement prevailed in cases of
      single tumors; para-aortal node involvement--lymph nodes. Recurrences were as
      frequent in the vaginal stump cupola (9.7%) as in the remaining parametrium
      (9.7%). It is important that endometrial carcinoma staging take into account the
      histological pattern and site of tumor in the uterine cavity in order to examine
      organs in which metastases are most likely to occur. Preoperative high-dosage
      brachytherapy should be conducted to minimize the likelihood of relapse.

PMID- 17195643
TI  - [Rationale for surgical treatment of octogenarians with lung cancer].
AB  - Lung cancer was treated by surgery in 17 patients (males--13, females--4) aged
      more than 80 years, i.e. 2% of surgical patients older than 70 (n-870). The chief
      death-causing factors were cardiovascular insufficiency and thromboembolism of
      the pulmonary artery.

PMID- 17195645
TI  - [Use of licopid and viferon in the course of radiotherapy for endometrial
      carcinoma].

PMID- 17195646
TI  - [Results of therapy in different groups of risk for superficial bladder cancer].
AB  - Approximately 10.0% of tumors occurs in the lower urinary tract and morbidity and
      lethality are constantly on the rise. Over 90% of such tumors registered in
      Europe and the USA is transitional cell carcinoma. Primary bladder cancer
      morbidity in Russian males rose by 4.0-4.6% in 1990-1997 while the share of
      patients with superficial bladder cancer (SBC) went up by 1.5% for the same
      period. According to the National Bladder Cancer Group, the rising incidence of
      relapsing SBC is associated with urothelial dysplasia, positive test for urinary
      sediment after therapy and occurrence of four or more tumors larger than 5 cm.
      Prevention of muscular invasion is vital in management of SBC. Sometimes, such
      aggressive modalities as early cystectomy or radiotherapy are recommended in
      cases of high risk for this pathology. Conversely, certain palliative measures,
      short of transurethral resection of the bladder and adjuvant intravesical
      therapy, are regarded as sufficient.

PMID- 17195647
TI  - [End-results of resection for distal gastric cancer].
AB  - End-results of surgery for stomach cancer conducted at the Institute Clinic have
      been evaluated. In 1982-2002, 260 patients with gastrointestinal tumors underwent
      subtotal distal resection of the stomach (Billroth-1) and another 220--Billroth
      2. Functional outcome was assessed in 122 (46.9%) (Billroth-1) and 78 (Billroth
      2). The end-results appeared to be identical: 5- and 10-year survival rate after
      Billroth-1 was 65.1 and 24.7%, and Billroth-2--63.4 and 27.1%, respectively.

PMID- 17195648
TI  - [Results of combined therapy for malignant tumors of the nasal cavity and
      accessory nasal sinus depending on the fractionation of preoperative
      radiotherapy].
AB  - Data on the treatment of 215 patients with locally advanced malignancies of the
      nasal cavity and accessory nasal sinus are presented. All patients received
      preoperative radiotherapy using different fractionation schemes under a total
      target dose (TTD) of 32-40 Gy. Surgery was carried out two weeks later. Whenever
      radicality of surgery was in doubt, postoperative gamma therapy included exposure
      to 2 Gy 5 times a week (TTD--30-40 Gy) (n=121). Group I (n-57) received radiation
      at standard fractionated dosage. In group II (n=66), fractionation, tentatively
      considered "dynamic" was used while, in group III, fractionation was dynamic in
      actual fact. In group IV (n=10), superfractionation (1+1 Gy) was employed in
      group V (n=6),--gamma-neutron therapy. Patients in group VI (n=51) were operated
      on as scheduled and received 5 Gy, twice a week (TTD--20 Gy). According to 5-year
      follow-up, the best results were obtained with the use of larger doses of
      preoperative radiation (groups II, III, VI). Postoperative radiotherapy proved
      ineffective and it would be useless unless ablative procedures were definitely
      faulty during surgery.

PMID- 17195649
TI  - [Chemoradiation therapy in conjunction with physical means of radiomodification
      for locally advanced laryngeal cancer].
AB  - The study deals with the results of examination and treatment of 1040 patients
      with cancer (T3-4N0-3M0) of larynx and laryngopharynx. Radiotherapy was given to
      358 patients concurrently with systemic polychemotherapy and different means of
      radiomodification. The remaining patients (682) receiving the same treatment
      minus systemic polychemotherapy were in control. Relapse-free (72.6%) and overall
      survival (82.7%) in the study group was significantly higher than in controls
      (54.7% and 63.4%, respectively) (p < 0.001). Moreover, an organ's function was
      preserved in 57.1% compared with 28.5% in control (p < 0.001).

PMID- 17195651
TI  - [Dysplasias and tumors of the thyroid gland].

PMID- 17195650
TI  - [Experience with gliatilin treatment of patients with intracranial neoplasia].

PMID- 17195652
TI  - [Cellular composition of the bone marrow and peripheral blood in patients with
      malignant non-Hodgkin's disease of the gastrointestinal tract].

PMID- 17195654
TI  - [Alternative (non-cytotoxic) strategies in antitumor therapy].

PMID- 17195653
TI  - [The birth centenary of Raisa Pavlovna Martynova].

PMID- 17195655
TI  - [Precancer-causing potential of chronic Helicobacter pylori-associated atrophic
      gastritis--measures of prevention].

PMID- 17195656
TI  - Cadherin-based resistance to Bacillus thuringiensis cotton in hybrid strains of
      pink bollworm: fitness costs and incomplete resistance.
AB  - Recessive resistance to Bacillus thuringiensis (Bt) cotton, Gossypium hirsutum
      L., in laboratory-selected strains of pink bollworm, Pectinophora gossypiella
      (Saunders), is associated with three resistance alleles (r1, r2, and r3) of a
      cadherin gene. Previous experiments based on measurement of fitness components in
      Bt-resistant and Bt-susceptible strains revealed that fitness costs and
      incomplete resistance are associated with resistance. Here, we used two hybrid
      strains of pink bollworm, each containing a mixture of susceptible and resistant
      individuals, and polymerase chain reaction (PCR) amplifications to test the
      association between cadherin genotype and fitness components for individuals
      sharing a common genetic background. All survivors on Bt cotton had two r
      alleles, confirming that recessive cadherin alleles are tightly linked with
      resistance to Bt cotton. On non-Bt cotton, significantly greater developmental
      time for rr than ss larvae indicated a recessive fitness cost, but costs did not
      affect survival or pupal weight. Incomplete resistance was manifested as longer
      developmental time, lower survival, and smaller pupal weight in rr individuals
      developing on Bt cotton compared with non-Bt cotton. As in previous experiments,
      no significant variation in performance on Bt cotton was detected among rr
      genotypes. However, a meta-analysis of data from seven experiments revealed that
      survival on Bt cotton relative to non-Bt cotton was lower in r2r3 and higher in
      r1r2 compared with the other rr genotypes. Assessment of fitness components
      associated with cadherin genotypes in hybrid strains of pink bollworm confirms
      that recessive resistance to Bt cotton is associated with recessive fitness costs
      and incomplete resistance.

PMID- 17195657
TI  - Spatial and temporal dynamics of overwintering Homalodisca coagulata (Hemiptera:
      Cicadellidae).
AB  - A 4-yr landscape-scale study was conducted to investigate spatial and temporal
      dynamics of overwintering Homalodisca coagulata (Say) (Hemiptera: Cicadellidae)
      in the lower San Joaquin Valley, California. Spatial structures of H. coagulata
      distributions were characterized with Moran's I index, and spatial associations
      between H. coagulata and the surrounding environment were investigated with a
      geographic information system. H. coagulata was caught consistently with sticky
      traps throughout the winter, and trap catches formed a distinctive peak in
      December or January, indicating active flight of H. coagulata during the winter.
      In 2000-2001, the mean +/-SE trap count was 4.8 +/- 1.21 per trap per wk, and H.
      coagulata trap catches were spatially autocorrelated within approximately 1.3 km.
      Approximately 49% of H. coagulata were caught in citrus, 23% in stone fruit, and
      11% in grape. After a control program began in spring 2001, the mean trap count
      was considerably lower (0.041 +/- 0.0004 per trap per wk), and no spatial
      autocorrelations were detected in 2001-2004. H. coagulata trap catch-crop
      associations also changed after initiation of the control program. Between 25 and
      38% of H. coagulata trap catches were from citrus, between 8 and 20% were from
      stone fruit, and between 11 and 25% were from grape. Potential for winter-season
      spread and management of Xylella fastidiosa Wells et al., a pathogen causing
      Pierce's disease, are discussed.

PMID- 17195658
TI  - Pathogenicity of three formulations of entomopathogenic fungi for control of
      adult Haematobia irritans (Diptera: Muscidae).
AB  - Powder formulations of three species of entomopathogenic fungi were evaluated for
      their pathogenic effect upon adult horn flies, Hematobia irritans (L.) (Diptera:
      Muscidae). Flies were treated with conidia and blastospores of the
      entomopathogenic fungi Beauveria bassiana (Bals.) Vuill. (strain GHA),
      Metarhizium anisopliae (Metschnikoff) Sorokin (strain ESCI), and Paecilomyces
      fimosoroseus (Wize) Brown & Smith (strain ARSEF 3581) in the laboratory. At 4 d
      postexposure, flies treated with B. bassiana had an average of 98.4% mortality
      versus 43.5% from treatment with M. anisopliae and 13.0% from treatment with P.
      fiimosoroseus. At 7 d postexposure, flies treated with B. bassiana had an average
      of 100.0% mortality compared with 73.0% from treatment with M. anisopliae and
      33.3% from treatment with P.fumosoroseus. Mean lethal time (LT50) was 2.70, 4.98,
      and 7.97 d for B. bassiana, M. anisopliae, and P. fiumosoroseus, respectively.
      Entomopathogenic fungi such as B. bassiana and M. anisopliae may have the
      potential for controlling populations of horn flies. These studies indicate that
      B. bassiana and M. anisopliae were not only pathogenic to adult horn flies, but
      they caused mortality in a short time.

PMID- 17195659
TI  - Effect of combining imidacloprid and diatomaceous earth with Beauveria bassiana
      on mole cricket (Orthoptera: Gryllotalpidae) mortality.
AB  - Sublethal doses of three orthopteran-derived strains of Beauveria bassiana
      (Balsamo) Vuillemin were topically applied to adult southern mole crickets,
      Scapteriscus borellii Giglio-Tos (Orthoptera: Gryllotalpidae), and tested in
      combination with substrate treatments of diatomaceous earth (DE) and
      imidacloprid. Crickets treated only with the high doses (10(8) conidia per
      cricket) of each of the three B. bassiana strains exhibited the shortest survival
      times as well as the highest percentage mortality at 28 d after treatment.
      However, these treatments did.not differ significantly from any of the
      diatomaceous earth combination treatments. Two of the strains tested, 5977 and
      3622, exhibited synergistic interactions with DE, whereas the third strain, GHA,
      was not significant for synergy. Mortality caused by the combination treatment
      was still greater than the expected additive effect. DE abrades the insect
      cuticle and absorbs cuticular lipids, aiding the entry of germinating conidia
      into the mole cricket hemocoel. None of the three strains exhibited synergy when
      combined with imidacloprid, and mortality of all combination treatments was less
      than additive. For strain 5977, there was an antagonistic interaction with
      imidacloprid. It was difficult to obtain <30% mortality for imidacloprid only
      treatments, which was considered the upper limit for sublethal doses. The mean
      percentage mortality caused by imidacloprid was 37.5%, and this high percentage
      made it difficult for any combination treatment to cause significantly more
      mortality than the expected additive effect. These results clarify the
      interactions of other control products with B. bassiana and provide a basis for a
      reduced pesticide approach to mole cricket control.

PMID- 17195660
TI  - Laboratory evaluation of entomopathogenic fungi Beauveria bassiana and
      Metarhizium anisopliae against puparia and adults of Ceratitis capitata (Diptera:
      Tephritidae).
AB  - Laboratory experiments were done to measure the pathogenicity of 10 autochthonous
      isolates of Beauveria bassiana (Balsamo) Vuill. and of five Metarhizium
      anisopliae (Metsch.) Sorok. toward puparia and adults of the Mediterranean fruit
      fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae). Although all isolates
      applied via inoculation of the fungal suspensions on the ventral surface of the
      abdomen were pathogenic to adults, with mortality rates ranging from 30 to 100%
      and average survival times (ASTs) from 6.5 to 8.6 d, when C. capitata puparia
      were immersed in the conidial suspensions, only B. bassiana Bb-1333 and EABb
      01/103-Su and M. anisopliae EAMa 01/58-Su isolates caused >50% mortality of
      puparia. In a second series of bioassays conducted on five selected isolates,
      adults were sprayed with four 10-fold concentrations ranging from 1.0 x 10(5) to
      1.0 x 10(8) colony-forming units (cfu)/ml. The median lethal concentrations
      (LC50) of the four most virulent isolates ranged from 4.9 x 10(5) to 2.0 x 10(6)
      cfu/ml with estimated time to kill 50% of the insects ranging from 4.6 to 5.3 d.
      The effect of a sublethal dose (ca. LD50) of either B. bassiana EABb 01/103-Su or
      M. anisopliae EAMa 01/58-Su isolate was studied by reciprocal crossing. Treatment
      with B. bassiana reduced fecundity and fertility at 6, 8, and 10 d after
      treatment, with fecundity and fertility reductions ranging from 20.0 to 71.2% and
      from 33.6 to 60.0%, respectively. These reductions occurred in pairing
      combinations of treated females with either treated or nontreated males. M.
      anisopliae was more effective in reducing fecundity and fertility at 6 d after
      treatment, with the reduction varying from 58.4 to 72.1% and from 28.6 to 45.9%,
      respectively. In addition, the first oviposition was significantly delayed for 1
      d in females treated by either fungal species. The above-mentioned five selected
      isolates were assayed against C. capitata puparia treated as late third instars
      in sterilized soil at 25'C under three moisture conditions (-0.1, -0.01, and 
      0.0055 MPa). At -0.01 MPa, all isolates were low pathogenic to C. capitata
      puparia, whereas significant differences in the puparia mortality occurred
      between isolates at -0.1 and -0.0055 MPa. The highest pupal mortalities ranged
      from 52.5 to 70.0%, as a function of soil moisture and were caused by EAMa 01/58
      Su and Bb-1333 isolates.

PMID- 17195661
TI  - Interactions over time between cereal leaf beetle (Coleoptera: Chrysomelidae) and
      larval parasitoid Tetrastichus julis (Hymenoptera: Eulophidae) in Utah.
AB  - The phenology of parasitism of the cereal leaf beetle, Oulema melanopus (L.)
      (Coleoptera: Chrysomelidae) by Tetrastichus julis (Walker) (Hymenoptera:
      Eulophidae) was studied in small grain fields from 2000 to 2005 in northern Utah,
      after release and redistribution of the partially bivoltine larval parasitoid
      during the 1990s. Host larvae first occurred in May, with peak infestation
      typically occurring in early to mid-June. Parasitism by overwintering females of
      T. julis was highest among earliest developing beetle larvae. Thereafter, rates
      of parasitism fell to low levels (5-10% or less) by the latter half of June, when
      heat accumulation had reached 280-350 degree-days (based on a minimum threshold
      of 8.9 degrees C). With the emergence of second generation parasitoids, rates of
      parasitism rose to levels approaching 100% among the relatively few late
      developing larvae of O. inelanopus. Clear and consistent differences over the
      years were not observed among different crops of small grains (barley, wheat, or
      oats) either in the phenology and intensity of beetle infestation, or in the rate
      of parasitism of beetle larvae. The rate of parasitism was especially high in
      2005, and an increase in the minimum level of parasitism (observed each year at
      mid-season) was apparent over the course of the study. These results indicate
      that the parasitoid has become well established and seems to be continuing to
      increase in its impact on O. melanopus in northern Utah, despite a relatively
      hostile environment of crop management, wherein most fields are plowed and disked
      annually.

PMID- 17195662
TI  - Irradiation as a phytosanitary treatment for white peach scale (Homoptera:
      Diaspididae).
AB  - Irradiation was examined as a potential phytosanitary treatment to control white
      peach scale, Pseudaulacaspis pentagona (Targioni-Tozzetti) (Homoptera:
      Diaspididae), a serious quarantine pest of papaya, Carica papaya L., in Hawaii.
      Dose-response tests were conducted with second-stage nymphs, adult females
      without eggs, and adult females with eggs at a series of irradiation doses
      between 60 and 150 Gy to determine the most tolerant stage. The adult female with
      eggs was the most tolerant stage. In large-scale validation tests 35,424 adult
      female scales with and without eggs irradiated at a dose of 150 Gy produced no F1
      generation adults with eggs. Irradiation treatment with a minimum absorbed dose
      of 150 Gy should provide quarantine security for white peach scale on exported
      papaya and other commodities.

PMID- 17195663
TI  - Comparison of sexual compatibility between laboratory and wild Mexican fruit
      flies under laboratory and field conditions.
AB  - The sexual compatibility between laboratory (LF) and wild (WF) strains of the
      Mexican fruit fly, Anastrepha ludens (Loew), was analyzed using analogous
      methodologies and experimental arenas under both laboratory and field conditions.
      Sexual compatibility was quantified with the following indices: the isolation
      index (ISI), male relative performance index (MRP), female relative performance
      index (FRPI), and the relative sterility index (RSI). ISI detected a certain
      level of incompatibility between strains under both laboratory and field
      conditions, because LF females tended to mate with LF males. LF mating
      performance was higher under laboratory than under field conditions. The relative
      performance indices for LF and the relative sterility index were higher in the
      laboratory than in the field. Differences between LF and WF in the times that
      males started calling and mating were observed in both environments. Importantly,
      WF males reduced their sexual activity under laboratory environments, whereas LF
      maintained similar activity levels in both conditions. The possible applications
      of the above-mentioned methods, not only to assess fly quality but also to
      determine the suitability of conditions in mass-rearing facilities, are
      discussed. Correlating laboratory quality to sexual behavior may contribute in
      the development of environmental parameters for mass-rearing facilities.

PMID- 17195664
TI  - Evaluation of Ostrinia nubilalis (Lepidoptera: Crambidae) neonate preferences for
      corn and weeds in corn.
AB  - Choice tests were conducted to determine feeding preferences of European corn
      borer, Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae), neonates for 15
      species of plants. Percentage of neonates accepting (found on) each leaf disc
      after 24 h was measured using choice tests. Initially, nine species of plants
      were evaluated. The following year, 10 plant species were evaluated during O.
      nubilalis first generation and 11 species during the second generation.
      Pennsylvania smartweed, Polygonum pennsylvanicum (L.), had the highest percentage
      of neonates accepting leaf discs in both years. Other plants with high acceptance
      rates included swamp smartweed, Polygonum amphibium L.; velvetleaf, Abutilon
      theophrasti Medicus; cocklebur, Xanthium strumarium L.; and yellow foxtail,
      Setaria glauca (L.). Corn, Zea mays L., consistently had low percentages of
      neonates accepting leaf discs along with common waterhemp, Amaranthus rudis
      Sauer. Implications these results may have on O. nubilalis host plant selection
      in central Iowa's corn dominated landscape are considered.

PMID- 17195665
TI  - A new blend of white sapote fruit volatiles as potential attractant to Anastrepha
      ludens (Diptera: Tephritidae).
AB  - The behavioral and electrophysiological responses of nonirradiated male and
      female Anastrepha ludens (Loew) (Diptera: Tephritidae), to white sapote,
      Casimiroa edulis Oerst. (Rutaceae), volatiles were investigated. Females flew
      upwind and landed more often on fruit than on artificial fruit in wind tunnel
      bioassays. Males flew upwind (but not landed) more frequently on fruit than on
      artificial fruit. Porapak Q volatile extracts of white sapote also elicited
      upwind flight and landing on artificial fruit for both sexes. Gas chromatography
      electroantennographic detection analysis of white sapote extracts revealed that
      antennae of both sexes responded to eight compounds. Two peaks were unidentified
      because they did not separate from the solvent. Subsequent peaks were identified
      by gas chromatography-mass spectrometry as styrene, myrcene, 1,2,4
      trimethylbenzene, 1,8-cineole, and linalool in a proportion of 50: 21: 0.5: 27:
      1.5, respectively. Eight peaks were tentatively identified as beta-trans-ocimene.
      The number of A. ludens captured in multilure traps baited with the synthetic
      white sapote blend was higher than the flies captured by the multilure unbaited
      traps (control) in field cages. However, the number of flies captured by traps
      baited with the white sapote blend was not different from that of flies captured
      by traps baited with hydrolyzed protein. Using standard chemical ecology
      techniques, we found potential attractants from wild sapote fruit for monitoring
      and management of A. ludens population.

PMID- 17195666
TI  - Impact of trap design, windbreaks, and weather on captures of European corn borer
      (Lepidoptera: Crambidae) in pheromone-baited traps.
AB  - Pheromone-baited traps are often used in ecological studies of the European corn
      borer, Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae). However, differences
      in trap captures may be confounded by trap design, trap location relative to a
      windbreak, and changes in local weather. The objectives of this experiment were,
      first, to examine differences in 0. nubilalis adult (moth) captures among the
      Intercept wing trap, the Intercept bucket/funnel UNI trap, and the Hartstack wire
      mesh, 75-cm-diameter cone trap (large metal cone trap) as well as among three
      cone trap designs. Second, we examined the influence of the location of the large
      metal cone trap relative to a windbreak on the number of moths captured. Third,
      we examined the relationship between nightly mean air temperature, relative
      humidity, wind speed, precipitation, and the number of moths captured in large
      metal cone traps. The number of moths captured was significantly influenced by
      trap design, with large metal cone traps capturing the most moths. Wing and
      bucket traps were ineffective. Differences among trap captures were significant
      among trap locations relative to a windbreak. Under strong (>14 kph) or moderate
      (7 <14 kph) wind speeds, traps located leeward of the windbreak captured the most
      moths, but when wind speeds were light (<7 kph), traps not associated with
      windbreaks captured the most moths. The multiple regression model fitted to the
      relationship between number of moths captured per Julian date and nightly weather
      patterns was significant. Nightly mean air temperature was the most influential
      parameter in the model, and its relationship with moth capture was positive.

PMID- 17195667
TI  - Bioactivity of neem, Azadirachta indica, against spittlebug Mahanarva fimbriolata
      (Hemiptera: Cercopidae) on sugarcane.
AB  - The effect of neem, Azadirachta indica A. Juss, on some biological parameters of
      Mahanarva fimbriolata (Stil) (Hemiptera: Cercopidae) was studied in the
      laboratory by using NeemAzal-T/S, Nimkol-LS, and an aqueous neem seed extract.
      Initially, the LC,, was estimated for nymphs. Later, nymphs fed on sugarcane,
      Saccharum officinarum L., roots were sprayed with the respective LC,, for each
      product. The adults were maintained in cages on sugarcane plants sprayed at the
      base with the maximum rate recommended commercially for the crop (3 liter/ha).
      Moistened cotton discs surrounding the base of the plant were used as oviposition
      substrates. The LCso values estimated for NeemAzal, Nimkol, and aqueous extract
      were 0.014, 0.225, and 0.611%, respectively. There was a reduction in spittlebug
      longevity, regardless of sex, in relation to the control. Males exposed to the
      neem products, and aqueous extract showed longevity reductions of approximately
      50%, whereas for females the reductions were 55-60%. The neem products and
      extract reduced fecundity by 75-85%. Morphological and physiological changes were
      observed in 9% of the eggs from individuals submitted to NeemAzal. Neem-based
      products, especially NeemAzal, have potential for the control of M. fimbriolata.

PMID- 17195668
TI  - Efficacy and persistence of rosemary oil as an acaricide against twospotted
      spider mite (Acari: Tetranychidae) on greenhouse tomato.
AB  - Efficacy of rosemary, Rosmarinus officinalis L., essential oil was assessed
      against twospotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae),
      as well as effects on the tomato, Lycopersicum esculatum Mill., host plant and
      biocontrol agents. Laboratory bioassay results indicated that pure rosemary oil
      and EcoTrol (a rosemary oil-based pesticide) caused complete mortality of spider
      mites at concentrations that are not phytotoxic to the host plant. The predatory
      mite Phytoseiulus persimilis Athias-Henriot is less susceptible to rosemary oil
      and EcoTrol than twospotted spider mite both in the laboratory and the
      greenhouse. Rosemary oil repels spider mites and can affect oviposition behavior.
      Moreover, rosemary oil and rosemary oil-based pesticides are nonpersistent in the
      environment, and their lethal and sublethal effects fade within 1 or 2 d. EcoTrol
      is safe to tomato foliage, flowers, and fruit even at double the recommended
      label rate. A greenhouse trial indicated that a single application of EcoTrol at
      its recommended label rate could reduce a twospotted spider mite population by
      52%. At that rate, EcoTrol did not cause any mortality in P. persimilis nor did
      it affect their eggs. In general, EcoTrol was found to be a suitable option for
      small-scale integrated pest management programs for controlling twospotted spider
      mites on greenhouse tomato plants.

PMID- 17195669
TI  - Comparative susceptibility of sweetpotato weevil (Coleoptera: Brentidae) to
      selected insecticides.
AB  - The response of sweetpotato weevil, Cylas formicarius (F.) (Coleoptera:
      Brentidae), to insecticides used for its control was tested in laboratory
      bioassays. A glass vial bioassay technique was used to determine the
      susceptibility of two cohorts of sweetpotato weevil to selected insecticides.
      Vials were treated with methyl parathion, bifenthrin, cyfluthrin, carbaryl, and
      phosmet. Sweetpotato weevils demonstrated a mortality response to increasing
      concentrations of all insecticides tested, and our results indicated decreases in
      susceptibility of the Louisiana cohort of sweetpotato weevil compared with the
      Texas cohort for all insecticides tested. Methyl parathion was the most toxic
      chemical tested for both cohorts, followed by the pyrethroids, cyfluthrin and
      bifenthrin. Phosmet exhibited moderate toxicity compared with other chemicals
      tested, whereas sweetpotato weevils were least susceptible to carbaryl.
      Significant differences in lethal concentration (LC)50 and LC90 values for
      cyfluthrin and bifenthrin, the LC50 values for methyl parathion and phosmet, and
      the LC90 values for carbaryl were observed between the two cohorts. This study
      documents baseline toxicological data for five insecticides in two populations of
      sweetpotato weevil and demonstrates that susceptibility to all insecticides
      tested is lower for the Louisiana population compared with the Texas population.

PMID- 17195670
TI  - Effects of nitrogen fertilizer applied before permanent flood on the interaction
      between rice and rice water weevil (Coleoptera: Curculionidae).
AB  - Nitrogen fertilizer was applied to rice, Oryza sativa L., before permanent flood
      to determine the interaction between rice and the rice water weevil,
      Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), through a series
      of experiments conducted over a 3-yr period in Texas and Louisiana. Both absolute
      and relative percentage of yield loss because of L. oryzophilus feeding was not
      affected by fertilizer rates in the Texas experiment. Absolute yield loss
      increased with nitrogen rates in 2001 and 2002 in the Louisiana experiment;
      however, percentage of yield loss was not affected. This finding suggests that
      nitrogen rate does not affect tolerance of rice to L. oryzophilus injury. In the
      Texas experiment, differences were detected for ratoon crop yield among nitrogen
      rates and insecticide that were applied at preflood on the main crop, indicating
      a carryover of fertilizer and insecticide effects from the main to the ratoon
      crop. L. oryzophilus populations tended to increase with nitrogen fertilizer in
      the Louisiana experiment. Our results show that farmers should not increase
      preflood nitrogen fertilizer to increase tolerance of rice to L. oryzophilus
      injury.

PMID- 17195671
TI  - Interactions among white spruce tannins, Bacillus thuringiensis subsp. kurstaki,
      and spruce budworm (Lepidoptera: Tortricidae), on larval survival, growth, and
      development.
AB  - The interactions among white spruce, Picea glauca (Moench) Voss, purified acetone
      tannin extracts (hydrolyzable and condensed tannin), Bacillus thuringiensis
      subsp. kurstaki Cry1A(c) delta-endotoxin strain HD-73 (Btk), and spruce budworm,
      Choristoneura fumiferana (Clemens) (Lepidoptera: Tortricidae) on larval survival,
      growth, and development were investigated over the whole larval feeding period by
      using artificial diet supplemented with three concentrations of Btk toxins per
      milliliter of diet (0, 0.021, and 1.72 microg/ml) and three concentrations of
      foliar tannin extract (0, 8, and 15% dry mass basis). At high Btk concentration,
      tannin antagonized Btk potency against spruce budworm by lowering Btk-related
      larval mortality from 83 to 43%. At moderate Btk concentration tannin did not
      affect Btk potency. Host tree tannins antagonized not only the lethal effects of
      Btk toxin but also sublethal Btk-related impacts in terms of larval development,
      pupal weight, relative consumption rate, and growth rate. When alone in the diet,
      tannin negatively affected larval survival, growth, and development. Maximum
      potency of tannins against spruce budworm larvae (60% mortality) was reached at
      dietary concentrations corresponding to what is found in the plant (8% dry mass).
      The addition of Btk toxin in food containing tannin reduced percentage of larval
      mortality by one-third, indicating that Btk toxin can antagonize tannin potency
      against the insect. Development of Btk transgenic spruce trees should consider
      the antagonistic effect the toxin may have on the resistance conferred by tannins
      that have evolved naturally in spruce trees.

PMID- 17195672
TI  - Sprayable microencapsulated sex pheromone formulation for mating disruption of
      oriental fruit moth (Lepidoptera: Tortricidae) in Australian peach and pear
      orchards.
AB  - Areawide mating disruption treatments have been effective in controlling
      infestation of oriental fruit moth, Grapholita molesta (Busck) (Lepidoptera:
      Tortricidae), in Australian pome and stone fruit orchards. Although successful,
      the areawide mating disruption program has been an expensive approach by using
      hand-applied Isomate dispensers. Sprayable microencapsulated (MEC) pheromone
      formulations that can be applied with standard spray equipment could
      substantially reduce the cost of application. Field trials conducted during two
      consecutive seasons (2002-2004) demonstrated that monthly applications of MEC-OFM
      phase V (3M Canada, London, Ontario, Canada) at a rate of 125 ml/ha (37.1 g
      [AI]/ha) in replicated 2-ha blocks of both peaches and pears reduced oriental
      fruit moth shoot tip and fruit damage as effectively as a single application of
      Isomate OFM Rosso hand-applied dispensers (500 dispensers per ha) and as or more
      effectively than standard broad-spectrum insecticide sprays. Fruit protection was
      achieved despite high oriental fruit moth population densities in both crops as
      measured by moth catches in terpinyl acetate food and pheromone traps. Similar
      numbers of oriental fruit moths were captured among all treatments in food traps
      but captures of males in pheromone traps were disrupted (96-99%) in pheromone
      treated blocks relative to controls. The results of this study suggest that
      microencapsulated formulations of pheromone could be effectively used in areawide
      mating disruption programs for oriental fruit moth in Australia as a cost-saving
      alternative to reservoir-style dispensers requiring labor-intensive hand
      application.

PMID- 17195673
TI  - Use of residue profile analysis to identify modes of insecticide activity
      contributing to control of plum curculio in apples.
AB  - Residue profile analysis techniques were developed, along with laboratory and
      field-based bioassays to describe the modes of insecticidal activity responsible
      for the control of the plum curculio, Conotrachelus nenuphar (Herbst), in apples
      (Malus spp.). Adult plum curculios were treated in laboratory topical bioassays
      to determine acute contact activity and lethal time for five insecticides.
      Azinphosmethyl had the highest levels of toxicity and shortest lethal time
      values, followed by the neonicotinoids thiacloprid, thiamethoxam, and
      imidacloprid, whereas indoxacarb had the highest LD50 and LT50 values for topical
      exposure. Field-based residual activity bioassays assessed adult mortality, and
      fruit and leaf injury from plum curculio exposed to 4 h, 7 d, and 14 d field-aged
      residues. All compounds caused significant levels of mortality to plum curculio
      when adults were exposed to fruit clusters 4 h post-application. Thiacloprid,
      thiamethoxam, and imidacloprid showed oviposition deterrence, antifeedant, and
      repellency effects in the 7- and/or 14 d residual bioassays and protected fruit
      in the absence of significant lethal activity. Indoxacarb maintained lethal
      activity throughout the study intervals, with the incidence of plum curculio
      feeding, suggesting that ingestion is an important mode of entry. For the
      neonicotinoids thiacloprid, thiamethoxam and imidacloprid plum curculio mortality
      was highly correlated with fruit and leaf surface residues. As surface residues
      declined, sublethal effects such as oviposition deterrence and antifeedant effect
      remained. The value of the plant-insect-chemistry triad model for describing the
      temporal dimensions of insecticidal modes of activity and understanding a
      compound's critical performance characteristics is discussed.

PMID- 17195674
TI  - Laboratory evaluation of flight performance of the plum curculio (Coleoptera:
      Curculionidae).
AB  - Flight performance of laboratory-reared adults of the plum curculio,
      Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), was investigated
      under controlled conditions by using a flight mill system. Across all insects
      tested (n=198), median values of total distance traveled, total flight time, and
      maximum uninterrupted flight time were 122.7 m day(-1), 23.5 min day(-1), and 2.0
      min, respectively. The latter result indicates that flight occurred primarily in
      short bursts. Although females had a significantly higher body mass than males,
      there were no significant differences in flight performance between the two
      sexes. Flight during the first 24-h test period (especially the first 6 h) was
      dominated by escape behavior, i.e., elevated levels of activity presumably
      associated with attempts by the insects to regain freedom of movement; during the
      second 24 h, flight activity was very limited throughout the late morning and
      afternoon, increased around sunset, and remained high during the night. All
      flight performance variables decreased linearly and significantly with insect age
      over the age range tested (2-16 d after emergence). Nutritional status also had a
      significant effect, whereby insects that had been provided with apples as a food
      source for 2 d after emergence showed considerably improved flight performance
      compared with those that had been given no food or only water during the same
      period. There was no significant effect of mating status on flight performance of
      male or female insects.

PMID- 17195675
TI  - Olive fruit fly (Diptera: Tephritidae) populations in relation to region, trap
      type, season, and availability of fruit.
AB  - Olive fruit fly, Bactrocera oleae (Gmelin), was monitored with adult captures by
      season and trap type, and was related to fruit volume and nonharvested fruit to
      elucidate the occurrence of the newly introduced pest in California. The highest
      numbers of adults captured in ChamP traps in olive trees, Olea europaea, were in
      October in an inland valley location, and in September in a coastal location.
      Comparisons of trap types showed that the number of olive fruit fly adults
      captured in Pherocon AM traps in a commercial orchard was significantly greater
      than in ChamP traps. A significantly greater number of females were captured in
      Pherocon AM traps with bait packets and pheromone lures than traps with pheromone
      lures alone, while a significantly greater number of adults and males were
      captured in traps with pheromone lures alone. Significantly more adults were
      captured in ChamP traps with bait packets and pheromone lures versus traps with
      bait packets alone. Fruit volume increased by four times from mid-June to mid
      November. Olive fruit fly was found to oviposit on small olive fruit <1 cm3
      shortly after fruit set, the maximum number of ovipositional sites per fruit
      occurred in October, and the greatest number of pupae and adults were reared from
      fruit collected in September and October. The highest numbers of pupae were
      collected from nonharvested fruit in March when high numbers of adults were
      captured in the same orchard.

PMID- 17195676
TI  - Laboratory evaluations of insecticide product efficacy for control of Cimex
      lectularius.
AB  - A susceptible, laboratory strain of bed bug, Cimex lectularius L., was used to
      determine the efficacy of insecticide products labeled or possessing a site label
      for bed bug control. Field strain bed bugs also were used to evaluate one
      insecticide product. The lethal time (LT),, values calculated for the laboratory
      strain bed bugs indicated that all of the pyrethroid products killed
      significantly faster than chlorfenapyr (0.5% [AIl; Phantom: BASF; LT50 = 10 d and
      9 h). lamda-Cyhalothrin (0.03%; Demand CS; Syngenta) was the fastest acting
      insecticide (LT50 = 20 min), followed by bifenthrin (0.02% [AI]; Talstar One,
      FMC; LT50 = 53 min), deltamethrin (0.06% [AI]; Suspend SC; Bayer; LT50 = 61 min),
      and permethrin (0.05%; Dragnet SFR; FMC; LT50 = 88 min). The field strain bed
      bugs exposed to deltamethrin had an LT50 value of 14 day 8 h, indicating that the
      field strain was significantly less susceptible to deltamethrin than the
      laboratory strain. Chlorfenapyr exposure did not prevent the laboratory strain
      bed bugs from mating and laying eggs, nor did it prevent the eggs from hatching
      during the 2-wk exposure period. Surprisingly, none of the insecticides tested,
      including the pyrethroids, were repellent to laboratory strain bed bugs. Bed bugs
      rested on pyrethroid-treated panels and remained in contact with the panels until
      they died (2 h). Chlorfenapyr was also not repellent to bed bugs, but it caused
      no mortality during the 2-h test period. This study suggests that although
      pyrethroids were effective for controlling laboratory strain bed bugs, there is
      the potential for significant resistance in field strains. This study also
      determined that pyrethroid products were not repellent to bed bugs and would not
      cause bed bug aggregations to scatter or avoid treated surfaces.

PMID- 17195677
TI  - Map position of phosphoglucomutase (Pgm) locus on autosome IV of house fly
      (Diptera: Muscidae).
AB  - We determined the map position of phosphoglucomutase (Pgm) locus on autosome IV
      of housefly, Musca domestica L. (Diptera: Muscidae), by using three and five
      point linkage test crosses. Test strains had visible mutant markers (car, bwb,
      cyw, and aabys). We analyzed 1738 offspring in total from two groups of single
      pair matings by electrophoresis. Here, we report the linkage of Pgm locus to
      autosome IV loci curly wing (cyw) and yellow eyes (ye) with recombination
      frequency of 16.9 and 1.1%, respectively. We combined the distances calculated
      from this study and the previously published data. An updated linkage map of the
      M. domestica L. Autosome IV was drawn based on combined data in terms of real map
      units obtained from the mapping function.

PMID- 17195678
TI  - Impact of small fitness costs on pest adaptation to crop varieties with multiple
      toxins: a heuristic model.
AB  - A deterministic two-locus model was used to examine how small fitness costs to
      individuals carrying resistance alleles could impact the risk of panmictic insect
      pest populations adapting to crop varieties that produced two distinct toxins.
      Parameters examined were (1) level of toxicity of each toxin, (2) initial
      frequencies of alleles for adaptation to the toxins, (3) percentage of population
      feeding on nontoxic plants, and (4) level of fitness cost associated with
      adaptation to each of the two toxins. Resistance to each toxin was assumed to be
      biochemically independent, controlled by a resistance coding allele at a single
      locus, and inherited as a partially recessive trait in the field. When plants are
      extremely toxic to the pest, effective refuge size is 10%, and there is a fitness
      cost to resistance alleles only when in homozygous form (5%), the pest population
      is never predicted to adapt to either toxin as long as the initial frequencies of
      the resistance alleles are below 0.05. Even if the initial frequency of the
      allele for adapting to one toxin is 0.95 when a two-toxin cultivar completely
      replaces a one-toxin cultivar, the model predicts that a low equilibrium allelic
      frequency will develop for both resistance alleles, as long as the frequency of
      the allele for adapting to the second toxin is initially 0.001 or less. If
      cultivars with one and two toxins are planted, the model predicts that resistance
      will develop. Nonrandom mating and stochastic variation within subpopulations
      also could lead to evolution of resistance.

PMID- 17195679
TI  - Evaluation of oviposition deterrence in management of resistance to transgenic
      corn by European corn borer (Lepidoptera: Crambidae).
AB  - We modified an existing model for European corn borer, Ostrinia nubilalis
      (Hubner) (Lepidoptera: Crambidae), population dynamics and genetics to evaluate
      the effectiveness of oviposition deterrence in transgenic fields for resistance
      management. We simulated two types of deterrence: one type has females reducing
      their oviposition because of lost opportunities to lay eggs (eggs lost), and the
      other type has the deterred females moving to the refuge to lay eggs. Oviposition
      deterrence was clearly effective in extending the time to resistance to
      transgenic corn (R allele) in the European corn borer, particularly when 80% or
      more of the eggs were deterred from being oviposited on the transgenic plants.
      With 90% of eggs deterred, the time required to reach 50% R-allele frequency
      increases 3.7- to 5.5-fold compared with the no-deterrence scenario. The time to
      50% R-allele frequency was similar for the two types of simulated deterrence, but
      the densities of the European corn borer were 100-fold higher when the deterred
      females oviposited in the refuge. The Y allele for insensitivity or resistance to
      deterrence never reached 50% within the 50-yr time line for these simulations
      except when the R allele was dominant and the Y allele was not recessive. The
      time to 50% Y-allele frequency was 33 and 26 yr when the Y allele was additive or
      dominant, respectively, when 50% of the eggs were deterred, but the time
      decreased to 18 and 16 yr when 90% of the eggs were deterred. The effectiveness
      of oviposition deterrence on time to resistance to transgenic insecticidal plants
      was not changed much when we altered our assumptions about behavior in a
      sensitivity analysis.

PMID- 17195680
TI  - Oil-soluble dyes for marking Spodoptera frugiperda (Lepidoptera: Noctuidae).
AB  - Although various biological aspects of Spodoptera frugiperda (J.E. Smith)
      (Lepidoptera: Noctuidae) have been examined, adult movement and dispersal of this
      insect pest is not well understood. Release-recapture techniques by using marked
      insects is a useful approach for dispersal studies; however, the marking
      technique should not significantly affect insect biology or behavior. Therefore,
      the effect of different concentrations of oil-soluble dyes (Solvent Blue 35 [C.I.
      61554], Sudan Red 7B [C.I. 26050], Sudan Black B [26150], Sudan Orange G [C.I.
      11920], and Sudan I 103624 [C.I. 12055]) on development, mortality, and fecundity
      of S. frugiperda was evaluated. Dyes were added to artificial diet used to feed
      larvae. Larval and pupal development and mortality, adult longevity, and female
      fecundity were evaluated. High concentrations (400 and 600 ppm) of all dyes led
      to longer larval and pupal stages. Adult life span and number of eggs were not
      affected by the dyes. Sudan Red 7B marked both adults and eggs very well. Solvent
      Blue 35 marked both adults and eggs, but the blue-marked eggs could not be
      distinguished from some bluish eggs laid by nonlabeled females. Adults and eggs
      were not adequately marked by the Sudan Black B, Sudan Orange G, and Sudan I
      103624 (a yellow dye).

PMID- 17195681
TI  - Modeling the impact of alternative hosts on Helicoverpa zea adaptation to
      bollgard cotton.
AB  - For highly polyphagous cotton, Gossypium hirsutum L., pests such as Helicoverpa
      zea (Boddie), a substantial portion of the larval population develops on
      noncotton alternative hosts. These noncotton hosts potentially provide a natural
      refuge for H. zea, thereby slowing the evolution of resistance to the Bacillus
      thuringiensis Berliner (Bt)-derived Cry1Ac protein present in Bollgard cotton.
      Here, we demonstrate how the measured contribution of such alternative hosts can
      be included in estimating the "effective refuge" present for H. zea and in
      modeling resistance evolution in this species. A single-gene, two-compartment
      model was used in which one compartment represented corn, Zea mays L., and cotton
      that express the Cry1Ac protein or similar proteins, and the other compartment
      was the effective refuge, made up of a weighted average of non-Bt cotton and
      noncotton hosts. The effective refuge was estimated for each of six generations
      of H. zea based upon available data on larval population densities on different
      hosts and cropping patterns. Model runs were performed for regions centered on
      three states: Georgia, Mississippi, and North Carolina. Three sets of fitness
      cost assumptions for the putative resistance gene were used: none, low, and
      moderate, with either recessive or additive inheritance for resistance and
      fitness costs. For Georgia and North Carolina, resistance was predicted to take
      >30 yr to evolve except in the absence of fitness costs. For Mississippi, results
      were sensitive to fitness costs: >30 yr with moderate costs, 7-14 yr with low
      costs, and 6-10 yr without such costs.

PMID- 17195682
TI  - High-level resistance to Bacillus thuringiensis toxin crylac and cadherin
      genotype in pink bollworm.
AB  - Resistance to transgenic cotton, Gossypium hirsutum L., producing Bacillus
      thuringiensis (Bt) toxin Cry1Ac is linked with three recessive alleles of a
      cadherin gene in laboratory-selected strains of pink bollworm, Pectinophora
      gossypiella (Saunders), a major cotton pest. Here, we analyzed a strain (MOV97-R)
      with a high frequency of cadherin resistance alleles, a high frequency of
      resistance to 10 microg of Cry1Ac per milliliter of diet, and an intermediate
      frequency of resistance to 1000 microg of Cry1Ac per ml of diet. We selected two
      strains for increased resistance by exposing larvae from MOV97-R to diet with
      1000 microg of Cry1Ac per ml of diet. In both selected strains, two to three
      rounds of selection increased survival at 1000 microg of CrylAc per ml of diet to
      at least 76%, indicating genetic variation in survival at this high concentration
      and yielding >4300-fold resistance relative to a susceptible strain. Variation in
      cadherin genotype did not explain variation in survival at 1000 microg of Cry1Ac
      per ml of diet, implying that one or more other loci affected survival at this
      concentration. This conclusion was confirmed with results showing that when
      exposure to Cry1Ac stopped, survival at 1000 microg of Cry1Ac per ml of diet
      dropped substantially, but survival at 10 microg Cry1Ac per ml of diet remained
      close to 100% and all survivors had two cadherin resistance alleles. Although
      survival at 1000 microg of Cry1Ac per ml of diet is not required for resistance
      to Bt cotton, understanding how genes other than cadherin confer increased
      survival at this high concentration may reveal novel mechanisms of resistance.

PMID- 17195683
TI  - Encasing mattresses in black plastic will not provide thermal control of bed
      bugs, Cimex spp. (Hemiptera: Cimicidae).
AB  - The suggestion that bed bug (Cimex spp.; Hemiptera: Cimicidae)-infested
      mattresses wrapped in black plastic and exposed to sunlight will be heated
      sufficiently to kill the bed bugs was tested. Two types of mattresses were
      tested: a thin mattress of solid foam rubber and a thick multilayered inner
      spring mattress. Temperature probes were placed on both upper and lower sides of
      the mattresses, which were wrapped in black plastic and placed outside on a
      summer day for >9 h wherein the ambient temperature peaked at 36.5 degrees C. The
      maximum recorded temperature on the upper (sun-exposed) sides was 85 degrees C
      for both mattresses, whereas lower side temperatures for the thick mattress never
      exceeded 35 degreesC, and some areas of the thin mattress failed to exceed
      36.50C. Therefore, with published thermal death points of 40-45 degrees C
      depending on exposure time, and opportunities for bed bugs to avoid lethal
      temperatures by retreating from hot zones, this technique seems to be not
      suitable for bed bug management.

PMID- 17195684
TI  - Rapid, high-throughput detection of azalea lace bug (Hemiptera: Tingidae)
      predation by Chrysoperla rufilabris (Neuroptera: Chrysopidae), using fluorescent
      polymerase chain reaction primers.
AB  - Azalea lace bugs, Stephanitis pyrioides (Scott) (Hemiptera: Tingidae), are the
      most common pest of azaleas (Rhododendron spp.) in nursery production and the
      landscape. Although pesticides are commonly used to control lace bugs, natural
      enemies can be a significant source of lace bug mortality. Lacewings (Neuroptera:
      Chrysopidae) are natural enemies of lace bugs and easily consume them in
      laboratory studies. Field studies on lacewing biocontrol of azalea lace bugs are
      underway; however, monitoring lacewing predation in a nursery environment by
      direct observation is impractical. Here, we describe a fluorescent-polymerase
      chain reaction method to estimate S. pyrioides consumption based on the gut
      contents of lacewing predators. Lace bug DNA was detected in fed lacewings up to
      32 h after ingestion. More than 80% of the ingested lace bugs were detected using
      our method with only one false positive result. The assay is both high-throughput
      and relatively inexpensive, making it a practical approach to documenting lace
      bug predation in the field.

PMID- 17195685
TI  - A rapid single-step multiplex method for discriminating between Trichogramma
      (Hymenoptera: Trichogrammatidae) species in Australia.
AB  - Inaccurate species identification confounds insect ecological studies. Examining
      aspects of Trichogramma ecology pertinent to the novel insect resistance
      management strategy for future transgenic cotton, Gossypium hirsutum L.,
      production in the Ord River Irrigation Area (ORIA) of Western Australia required
      accurate differentiation between morphologically similar Trichogramma species.
      Established molecular diagnostic methods for Trichogramma identification use
      species-specific sequence difference in the internal transcribed spacer (ITS)-2
      chromosomal region; yet, difficulties arise discerning polymerase chain reaction
      (PCR) fragments of similar base pair length by gel electrophoresis. This
      necessitates the restriction enzyme digestion of PCR-amplified ITS-2 fragments to
      readily differentiate Trichogramma australicum Girault and Trichogramma pretiosum
      Riley. To overcome the time and expense associated with a two-step diagnostic
      procedure, we developed a "one-step" multiplex PCR technique using species
      specific primers designed to the ITS-2 region. This approach allowed for a high
      throughput analysis of samples as part of ongoing ecological studies examining
      Trichogramma biological control potential in the ORIA where these two species
      occur in sympatry.

PMID- 17195686
TI  - Alpha-amylase activity of Rhyzopertha dominica (Coleoptera: Bostrichidae) reared
      on several wheat varieties and its inhibition with kernel extracts.
AB  - Total progeny of Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae) reared on
      10 wheat, Triticum aestivum L., varieties was evaluated. Higher amylase
      activities were detected in populations with few individuals, whereas the
      opposite was observed in higher populations. As protein ingested increased,
      reproductive success increased. However, consumption of wheat protein was
      inversely correlated with amylase activity levels (r = -0.66). Amylase activity
      in homogenates of R. dominica populations showed variable inhibition by wheat
      extracts prepared from wheat varieties on which they were reared. Insect
      populations with lowest amylase activities were inhibited more by wheat extracts
      than those with higher amylase activity (r = -0.77). An electrophoretic analysis
      revealed four phenotypes showing combinations of three isoamylases (Rm 0.70,
      0.79, and 0.90) in different populations of R. dominica. Some of the insect
      progeny that emerged from resistant wheat varieties contained the three
      isoamylases, whereas progeny that emerged from the most susceptible varieties
      showed reduced activity of isoamylases 0.70 or 0.90. These results suggest that
      the alpha-amylase activity levels and the composition of isoamylases in R.
      dominica populations are modulated by diet and that the alpha-amylase inhibitory
      activity of the wheat kernels influences these variations.

PMID- 17195687
TI  - Response of resistant and susceptible barley to infestations of five Diuraphis
      noxia (Homoptera: Aphididae) biotypes.
AB  - Since 2003, four new biotypes of the Russian wheat aphid, Diuraphis noxia
      (Kurdjumov) (Homoptera: Aphididae), RWA2-RWA5, have been discovered that have the
      ability to damage most of the wheat germplasm resistant to the original Russian
      wheat aphid population (RWA1). Barley germplasm lines with resistance to RWA1
      have not yet been evaluated against the newest biotypes. Our study compared how
      biotypes RWA1-RWA5 affected the growth and leaf damage of RWA1-resistant
      germplasm (STARS 9301B, STARS 9577B), moderately resistant germplasm (MR-015),
      and susceptible varieties (Schuyler, Harrington, and Morex) under greenhouse
      conditions. Russian wheat aphid population levels also were determined 14 d after
      plant infestation. STARS 9301B exhibited strong resistance by showing only small
      differences in leaf damage and growth parameters from the feeding by the
      biotypes. STARS 9577B showed greater differences in damage by the Russian wheat
      aphid biotypes than STARS 9301B, yet, the ratings were still within the resistant
      category (e.g., chlorosis rating 2.3-4.9). Leaf chlorosis ratings for MR-015
      ranged from 5.0 to 6.9 and fell within the moderately resistant to susceptible
      categories for all the biotypes. The greatest difference in leaf chlorosis
      occurred in Morex where RWA2 showed less virulence than the other biotypes.
      Feeding by the Russian wheat aphid biotypes produced only small differences in
      leaf rolling and plant growth within plant entries. Population levels of the
      Russian wheat aphid biotypes did not differ within barley entries (n = 610-971)
      at the termination of the study (14 d). From our research, we conclude that the
      new Russian wheat aphid biotypes pose no serious threat to the key sources of
      resistance in barley (STARS 9301B and 9577B).

PMID- 17195688
TI  - Host plant resistance in romaine lettuce affects feeding behavior and biology of
      Trichoplusia ni and Spodoptera exigua (Lepidoptera: Noctuidae).
AB  - Lettuce quality and yield can be reduced by feeding of several lepidopterous
      pests, particularly cabbage looper, Trichoplusia ni (Hubner), and beet armyworm,
      Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae). Host plant resistance to
      these insects is an environmentally sound adjunct to conventional chemical
      control. In this study we compared the survival, development, and feeding
      behavior of cabbage looper and beet armyworm on two romaine lettuce cultivars,
      resistant 'Valmaine' and susceptible 'Tall Guzmaine'. Larval mortality of both
      species was significantly higher on resistant Valmaine than on susceptible Tall
      Guzmaine. The average weight per larva after feeding for 1 wk on Tall Guzmaine
      plants was 6 times (beet armyworm) and 2 times (cabbage looper) greater than that
      of larvae feeding on Valmaine plants. Significant reduction in larval growth on
      Valmaine compared with that on Tall Guzmaine resulted in a 5.9- (beet armyworm)
      and 2.6-d (cabbage looper) increase in larval duration and almost a 1-d increase
      in pupal duration. Average pupal and adult weights and successful pupation of
      cabbage looper and beet armyworm were reduced on Valmaine compared with Tall
      Guzmaine. The sex ratio of progeny did not deviate from 1:1 when larvae were
      reared on either Valmaine or Tall Guzmaine. The fecundity of cabbage looper and
      beet armyworm adults that developed from larvae reared on Valmaine was about one
      third that of adults from Tall Guzmaine, but adult longevity did not
      significantly differ on the two lettuce cultivars. The two insect species showed
      different feeding preferences for leaves of different age groups on Valmaine and
      Tall Guzmaine. Cabbage loopers cut narrow trenches on the leaf before actual
      feeding to block the flow of latex to the intended site of feeding. In contrast,
      beet armyworms did not trench. The different feeding behavior of the two species
      on Valmaine may explain the superior performance of cabbage looper compared with
      beet armyworm.

PMID- 17195689
TI  - Decreased whorl and ear damage in nine mon810 Bacillus thuringiensis (Bt)
      transgenic corn hybrids compared with their non-Bt counterparts.
AB  - We examined nine pairs of near-isogenic hybrids of Bacillus thuringiensis (Bt)
      and non-Bt corn, Zea mays L., at two locations in 1999 and three locations in
      2000 to compare the effects of Bt toxins on damage caused by Helicoverpa zea
      (Boddie) to whorl stage field corn, and ear damage at harvest, as well as yield.
      We found that whorl damage was less in all Bt hybrids compared with their non-Bt
      counterparts each year and at each location. Differences in ear damage between Bt
      and non-Bt hybrids, however, differed in 1999 and 2000. In 1999, only one Bt
      hybrid, NC+5788Bt, had less ear damage than its non-Bt counterpart at the dryland
      site, whereas four Bt hybrids, C8120Bt, P31B13Bt, P33VO8Bt, and NC+5788Bt, had
      less damage at the irrigated site. In 2000, most Bt hybrids had less ear damage
      than their non-Bt counterparts at each location. Differences in whorl damage did
      not translate into yield differences. However, variations in ear damage were
      partially reflected in yield differences. In 1999, P31B13Bt and P33V08Bt had
      higher yields than their non-Bt counterparts at both sites, whereas in 2000 all
      Bt hybrids had higher yields. Also, although whorl damage was not correlated with
      yield, ear damage was negatively correlated with yield; increasing ear damage by
      H. zea decreased yield for Bt and non-Bt hybrids alike. Overall, depending on
      location and year, each centimeter of H. zea ear damage reduced yield by between
      2 and 13%.

PMID- 17195690
TI  - Evaluation of fixed sample-size plans for Plutella xylostella (Lepidoptera:
      Plutellidae) on broccoli crops in Australia.
AB  - Fixed sample-size plans for monitoring Plutella xylostella (L.) (Lepidoptera:
      Plutellidae) on broccoli and other Brassica vegetable crops are popular in
      Australia for their simplicity and ease of application. But the sample sizes used
      are often small, approximately 10-25 plants per crop, and it may be that they
      fail to provide sufficient information upon which to base pest control decisions.
      We tested the performance of seven fixed sample-size plans (10, 15, 20, 30, 35,
      40, and 45 plants) by resampling a large data set on P. xylostella in commercial
      broccoli crops. For each sample size, enumerative and presence-absence plans were
      assessed. The precision of the plans was assessed in terms of the ratio of the
      standard error to the mean; and at least 45 and 35 samples were necessary for the
      enumerative and presence-absence plans, respectively, to attain the generally
      accepted benchmark of < or = 0.3. Sample sizes of 10-20 were highly imprecise. We
      also assessed the consequences of classifications based on action thresholds
      (ATs) of 0.2 and 0.8 larvae per plant for the enumerative case, and 0.15 and 0.45
      proportion of plants of infested for the presence-absence case. Operating
      characteristic curves and investigations of the frequency of correct decisions
      suggest improvements in the performance of plans with increased sample size. In
      both the enumerative and presence-absence cases, the proportion of incorrect
      decisions was much higher for the lower of the two ATs assessed, and type II
      errors (i.e., failure to suggest pest control upon the AT is exceeded) generally
      accounted for the majority of this error. Type II errors are the most significant
      from a producer's standpoint. Further consideration is necessary to determine
      what is an acceptable type II error rate.

PMID- 17195691
TI  - Sampling plan for Diaphania spp. (Lepidoptera: Pyralidae) and for hymenopteran
      parasitoids on cucumber.
AB  - The objective of this work was to determine the best technique, sampling unit,
      and the number of samples to compose a conventional sampling plan for the
      cucurbit borers, Diaphania spp. (Lepidoptera: Pyralidae), and for hymenopteran
      parasitoids on cucumber. This research was carried out in 10 commercial cucumber
      crops fields from July to December 2000 in Tocantins, Minas Gerais State, Brazil
      (21 degrees 11' 15" S; 42 degrees 03' 45" W; altitude 363 m). The sampling
      methods studied were beating on a tray, direct counting of insects on the lower
      leaf surface, and whole leaf collection. Three sampling units also were studied:
      leaves from a branch located in the apical, median, or basal third of the canopy.
      The best sampling systems, which included the best technique and sampling unit,
      were determined based on the relative variance and the economic precision of the
      sampling. Once the best sampling systems were established, the numbers of samples
      to compose the conventional sampling plans were determined. The more suitable
      sampling system for the larvae of Diaphania spp. in cucumber plants was beating a
      leaf of the median third of the canopy on a plastic tray. One leaf must be
      sampled for every 50 plants in a crop. The more suitable sampling system for
      hymenopteran parasitoids in cucumber plants was to directly count the adults on
      one leaf of the median third of the canopy. One leaf must be sampled for every 74
      plants in a crop.

PMID- 17195693
TI  - Spatiotemporal clustering and association of Ephestia kuehniella (Lepidoptera:
      Pyralidae) and two of its parasitoids in bulk-stored wheat.
AB  - To assess the spatiotemporal distribution of insects in a flat storage containing
      wheat (Triticumn spp.), probe traps were suspended in the wheat bulk and
      inspected for captured insects at 15-d intervals, from June 2001 to August 2002.
      The grain bulk was 1 m in height, and traps were placed at the upper and the
      lower 0.5 m of the bulk. During the entire trapping period, 17 insect taxa were
      recorded. The most abundant species were Ephestia kuehniella Zeller (Lepidoptera:
      Pyralidae) and its larval parasitoids Harbobracon hebetor (Say) (Hymenoptera:
      Braconidae) and Venturia canescens (Gravenhorst) (Hymenoptera: Ichneumonidae).
      Most individuals were found in the upper bulk part. The highest E. kuehniella
      trap catches were found between August and November 2001 and during June and July
      2002. Of the two parasitoids, H. hebetor was more abundant than V. canescens,
      with the exception of winter and early spring, when both species occurred at low
      numbers, especially H. hebetor. Spatial analysis by distance indices (SADIE)
      spatiotemporal analysis showed significant clustering of species, especially
      during summer and autumn. Early in the season and during spring 2002, at low host
      numbers, V. canescens occupied the locations where E. kuehniella mainly
      aggregated, but with the increase of E. kuehniella population, H. hebetor
      occupied these host groups and replaced V canescens. Although the two parasitoids
      competed for the same host species, both species coexisted in the storage
      facility during the entire trapping period.

PMID- 17195692
TI  - Within-plant distribution and binomial sampling of Pentalonia nigronervosa
      (Hemiptera: Aphididae) on banana.
AB  - The banana aphid, Pentalonia nigronervosa Coquerel (Hemiptera: Aphididae),
      infests banana (Musa spp.) worldwide. Pentalonia nigronervosa is the vector of
      Banana bunchy top virus (family Nanoviridae, genus Babuvirus) the etiological
      agent of Banana bunchy top disease (BBTD). BBTD is currently the most serious
      problem affecting banana in Hawaii. Despite the importance of this vector
      species, little is known about its biology or ecology. There are also no sampling
      plans available for P. nigronervosa. We conducted field surveys to develop a
      sampling plan for this pest. Ten plots were surveyed on seven commercial banana
      farms on the island of Oahu, HI, for the presence of P. nigronervosa on banana
      plantlets. We found aphids more frequently near the base of plants, followed by
      the newest unfurled leaf at the top of the plant. Aphids were least likely to be
      located on leaves in between the top and bottom of the plant. Aphid infestation
      on surveyed plots ranged from 8 to 95%. We developed a sequential binomial
      sampling plan based on our surveys. We also discovered that the within-plant
      distribution of P. nigronervosa is an important factor to consider when sampling
      for this pest. Our sampling plan will assist in the development of sustainable
      management practices for banana production.

PMID- 17195695
TI  - Endocoprid activity of Aphodius fossor (Coleoptera: Scarabaeidae) related to
      bovine dung decomposition in a mixed grass prairie.
AB  - Aphodius fossor (L.) (Coleoptera: Scarabaeidae), a common endocoprid dung beetle
      in southeastern Wyoming, may have a survival strategy to maintain dung pad
      integrity and moisture crucial to larval survival in an arid climate (annual
      precipitation <30 cm). Typically, A. fossor seems to contribute little to dung
      pad decomposition, because inhabited dung pads seem to be intact and weigh
      approximately the same as uninhabited pads, even after 1 yr on pasture. To assess
      the role of A. fossor in dung pad decomposition and nutrient recycling,
      artificially formed bovine dung pads were inoculated with five pairs of adult A.
      fossor. After 40 d, A. fossor activity had no measurable effect on external
      surface area or moisture retention within the dung pad cores. Pads inhabited by
      A. fossor weighed significantly more than did control pads on most weigh dates of
      the experiment, possibly because of incorporation of soil particles at the
      dung/soil interface. Externally, A. fossor-inhabited dung pads seemed intact;
      however extensive tunneling was evident throughout the core of the pad leaving an
      intact, protective crust. A. fossor activity increased microbial biomass carbon
      in the soil beneath the dung pad. Levels of total nitrogen (N) and carbon (C)
      decreased in the pads but increased in soil beneath the pads. Dung in the core
      and in the crust of pads with A. fossor had significantly less total N than pads
      with no beetles and total C was significantly lower in the crust.

PMID- 17195694
TI  - Effects of shelf architecture and parasitoid release height on biological control
      of Plodia interpunctella (Lepidoptera: Pyralidae) eggs by Trichogramma deion
      (Hymenoptera: Trichogrammatidae).
AB  - The effects of shelving type, packaging, and release height on success of
      Trichogramma deion Pinto & Oatman (Hymenoptera: Trichogrammatidae) parasitizing
      Plodia interpunctella (Hubner) (Lepidoptera: Pyralidae) eggs was studied under
      laboratory conditions. In trials on multipletiered gondola-type or open shelving
      units, with or without packaging, foraging success was evaluated by comparing
      parasitism and total mortality rates of sentinel egg disks among shelves after a
      single point-release of T. deion. Results showed that T. deion parasitized more
      egg disks and killed more total eggs on open shelves than on gondola shelving.
      The presence of packaging had no effect on parasitoid foraging on open shelves;
      however, packaging did interfere with parasitism of P. interpunctella eggs on
      gondola shelving. Egg parasitism and mortality patterns among shelves were not as
      evenly distributed on gondola-type shelving compared with open shelving. On
      gondola shelves without packages, changing the release point of T. deion from the
      middle to the lowest shelf shifted the distribution of parasitism toward the
      floor. Gondola shelving, especially in the presence of packaging, reduced
      foraging efficiency of T. deion for P. interpunctella eggs. Thus, to attain
      adequate control of P. interpunctella, it may be necessary to use two release
      heights on gondola shelving.

PMID- 17195696
TI  - Identification of instars of Hypera postica using chaetotaxy.
AB  - A new method using chaetotaxy for identification of instars of Hypera postica
      (Gyllenhal) is presented and compared with earlier methods. I recommend a
      combined method using separation of small (first and second instars) and large
      (third and fourth instars) followed by identification of particular instars by
      using chaetotaxy.

PMID- 17195697
TI  - Immunogenicity and reactogenicity of primary immunization with a novel combined
      Haemophilus influenzae Type b and Neisseria meningitidis Serogroup C-tetanus
      toxoid conjugate vaccine coadministered with a Diphtheria-tetanus-acellular
      Pertussis-hepatitis B-inactivated poliovirus vaccine at 2, 4 and 6 months.
AB  - BACKGROUND: This phase II study evaluated the immunogenicity and reactogenicity
      of primary vaccination with a novel Hib-MenC conjugate vaccine (GlaxoSmithKline
      [GSK] Biologicals) coadministered with DTPa-HBV-IPV (GSK Biologicals) at 2, 4 and
      6 months. METHODS: Healthy infants were randomized to receive Hib-MenC
      coadministered with DTPa-HBV-IPV (N = 117) or MenC-CRM (Wyeth) coadministered
      with DTPa-HBV-IPV/Hib (GSK Biologicals; N = 120) at 2, 4 and 6 months. Antibody
      concentrations were measured before vaccination and after doses 2 and 3.
      Solicited local and general symptoms, unsolicited symptoms and serious adverse
      events (SAEs) were recorded. RESULTS: All subjects in the Hib-MenC group had
      seroprotective titers of anti-PRP antibodies (>or=0.15 microg/mL) and SBA-MenC
      titers (>or=1:8) 1 month after the third dose. These responses were noninferior
      to those seen in the control group, in which a 99.1% seroprotection rate was
      observed for both Hib and MenC. At that time, anti-PRP and SBA-MenC GMTs were
      significantly higher in the Hib-MenC group (12.8 microg/mL and 2467.1 microg/mL,
      respectively) than in the control group (3.8 microg/mL and 1833.7 microg/mL).
      High seroprotection rates were already observed after the second dose of Hib
      MenC; 96.4% and 100% of subjects were seroprotected to Hib and MenC,
      respectively. Immune responses to coadministered antigens were unimpaired;
      seroprotection/vaccine response rates >or=96.5% were recorded postdose 3 in the
      Hib-MenC group. No differences in reactogenicity were seen between the 2 study
      groups. CONCLUSIONS: Coadministration of a Hib-MenC conjugate vaccine with DTPa
      HBV-IPV is well tolerated and immunogenic, and does not impair the immune
      response to any of the coadministered antigens.

PMID- 17195698
TI  - Maintenance azithromycin treatment in pediatric patients with cystic fibrosis:
      long-term outcomes related to macrolide resistance and pulmonary function.
AB  - BACKGROUND: Maintenance azithromycin therapy may improve pulmonary function in
      patients with cystic fibrosis (CF) with Pseudomonas aeruginosa infection because
      of its antiinflammatory properties. However, azithromycin therapy might increase
      macrolide resistance in Staphylococcus aureus cultured from respiratory
      secretions. We studied the emergence of macrolide resistance in S. aureus and
      correlated this to pulmonary function decline in pediatric patients with CF on
      daily azithromycin therapy. METHODS: Respiratory cultures of 100 patients with CF
      were analyzed for S. aureus colonization and its resistance pattern before and
      during 3 years after initiation of azithromycin maintenance therapy. Mean annual
      change in forced expiratory volume as percent of predicted (FEV1 %) was
      calculated to compare pulmonary function before and after azithromycin therapy.
      RESULTS: Staphylococcal colonization did not significantly decrease after
      initiation of azithromycin (50% versus 48%). Before start of therapy, 10% of
      patients with staphylococcal colonization had macrolide-resistant strains.
      Staphylococcal resistance increased to 83% in the first year; 97% in the second
      and 100% in the third year after initiation of azithromycin therapy (P < 0.001).
      Half of macrolide-resistant S. aureus comprised the macrolide-lincosamide
      streptogramin phenotype. Percent forced expiratory volume in 1 second improved in
      the first year after initiation of azithromycin (mean annual change: -4.75%
      before versus +3.09% after initiation; P < 0.01) but decreased during the second
      and third years after initiation (-5.15% and -3.65%, respectively). Emergence of
      macrolide-resistant S. aureus was not related to pulmonary function decline.
      CONCLUSION: Maintenance azithromycin therapy in patients with CF leads to
      macrolide resistance in nearly all S. aureus carriers. Pulmonary function
      improvement after initiation of azithromycin therapy seems to be temporary and
      appears not to be related to macrolide resistance of S. aureus.

PMID- 17195699
TI  - Absence of an association between Mycobacterium tuberculosis genotype and
      clinical features in children with tuberculous meningitis.
AB  - OBJECTIVES: Animal studies point to increased virulence of certain mycobacterial
      strains, notably those of the Beijing genotype. There are limited data on
      mycobacterial genotypic diversity in children with tuberculous meningitis (TBM).
      We investigated mycobacterial genotypic diversity in children with TBM and
      analyzed the relationship among genotype, clinical presentation and outcome.
      PATIENTS AND METHODS: Data were extracted from an ongoing prospective study on
      children with confirmed TBM from 1992 through 2003 at a referral hospital in the
      Western Cape Province, South Africa. Mycobacterial isolates were genotyped by
      standardized restriction fragment length polymorphism methodology. Clinical data
      at diagnosis, inflammatory progression during the first month of antituberculosis
      therapy and neurologic outcomes after 6 months of therapy were analyzed according
      to the principal genetic group of the strain and the presence of the Beijing
      strain, respectively. RESULTS: Fifty-nine children were included (median age at
      diagnosis, 23 months); 37 presented with stage II and 22 with stage III presented
      with TBM. At completion of antituberculosis therapy, 6 children were
      neurologically normal, 22 were moderately neurologically impaired, 23 were
      severely neurologically impaired and 6 children died; detailed outcomes were not
      available in 2 children. All 3 principal genetic groups were represented (group
      1, 27.1%; group 2, 59.3%; group 3, 13.6%); the most prevalent strains were of the
      Beijing genotype (family 29; 25.4%), followed by family 28 (10.2%) and family 11
      (8.5%). Predictors of poor neurologic outcome included advanced disease at
      diagnosis and male gender. There was no association between the principal genetic
      group of the strain or the presence of the Beijing genotype, and clinical
      presentation or outcome. CONCLUSIONS: We found no association between
      Mycobacterium tuberculosis genotypes and clinical presentation or outcome.

PMID- 17195700
TI  - Sporadic campylobacter infection in infants: a population-based surveillance case
      control study.
AB  - BACKGROUND: Campylobacter is an important cause of foodborne illness in infants
      (younger than 1 year of age), but little is known about the sources of infection
      in this age group. METHODS: Eight sites in the Foodborne Diseases Active
      Surveillance Network (FoodNet) participated in a 24-month population-based case
      control study conducted in 2002-2004. Cases were infants with laboratory
      confirmed Campylobacter infection ascertained through active laboratory
      surveillance, and controls were infants in the community. RESULTS: We enrolled
      123 cases and 928 controls. Infants 0-6 months of age with Campylobacter
      infection were less likely to be breast-fed than controls [odds ratio (OR); 0.2;
      95% confidence interval (CI), 0.1-0.6]. Risk factors for infants 0-6 months of
      age included drinking well water (OR 4.4; CI, 1.4-14) and riding in a shopping
      cart next to meat or poultry (OR 4.0; CI, 1.2-13.0). Risk factors for infants 7
      11 months of age included visiting or living on a farm (OR 6.2; CI, 2.2-17),
      having a pet with diarrhea in the home (OR 7.6; CI, 2.1-28) and eating fruits and
      vegetables prepared in the home (OR 2.5, CI 1.2-4.9). Campylobacter infection was
      associated with travel outside the United States at all ages (OR 19.3; CI, 4.5
      82.1). CONCLUSIONS: Several unique protective and risk factors were identified
      among infants, and these risk factors vary by age, suggesting that prevention
      measures be targeted accordingly. Breast-feeding was protective for the youngest
      infants and should continue to be encouraged.

PMID- 17195701
TI  - Comparative effects of single-dose ceftriaxone versus three oral antibiotic
      regimens on stool colonization by resistant bacilli in children.
AB  - OBJECTIVE: The use of short-term intramuscular ceftriaxone for pediatric
      ambulatory conditions raises concerns regarding the promotion of resistance among
      colonizing enteric bacteria. This study was designed to assess the prevalence of
      stool colonization with resistant Gram-negative bacilli after single-dose
      ceftriaxone treatment compared with other regimens for acute otitis media.
      METHODS: Children age 3 months to 7 years and diagnosed with acute otitis media
      were randomized to receive treatment with single-dose ceftriaxone or with oral
      cefprozil, amoxicillin or azithromycin. Stool samples were obtained at enrollment
      and then 3-5 days, 10-14 days, and 28-30 days after therapy was initiated and
      screened for the presence of facultative Gram-negative bacilli resistant to
      ceftriaxone, cefprozil, amoxicillin, piperacillin, piperacillin-tazobactam and
      tobramycin. Mean prevalence of colonization by resistant organisms for each
      treatment group was compared at each time point. RESULTS: One thousand nine
      subjects were enrolled. The prevalence of colonization by a Gram-negative
      bacillus resistant to at least 1 of the screening antibiotics decreased after
      receipt of ceftriaxone but returned close to values measured at study entry by 30
      days. A qualitatively similar pattern was noted for the 3 other regimens, but a
      quantitatively greater decrease in the prevalence of colonization by a resistant
      bacterium was noted at the 3- to 5-day and 10- to 14-day visits among
      azithromycin recipients (P < 0.001). Colonization by a Gram-negative bacillus
      resistant specifically to ceftriaxone was unusual at each study visit, regardless
      of treatment assignment. CONCLUSIONS: A single intramuscular dose of ceftriaxone
      had a similar effect on the prevalence of antibiotic-resistant Gram-negative
      facultative bacilli in the stool of healthy children when compared with commonly
      used oral agents.

PMID- 17195702
TI  - The effect of changing from whole-cell to acellular pertussis vaccine on the
      epidemiology of hospitalized children with pertussis in Canada.
AB  - BACKGROUND: Between July 1997 and April 1998, universal childhood immunization
      programs in Canada changed from using a whole-cell pertussis to a 5-component
      acellular pertussis-containing vaccine. To assess effects on pertussis
      epidemiology of this nationwide change, we analyzed hospitalizations during 1991
      2004 using the Canadian Immunization Monitoring Program, Active (IMPACT)
      pertussis database. METHODS: IMPACT is an active surveillance network based in 12
      pediatric tertiary-care hospitals across Canada. Characteristics of hospitalized
      cases of pertussis were compared by type of vaccine received or by birth date (if
      immunization records were unavailable or the child was unvaccinated). Age
      stratified incidence rates were calculated by year and vaccine type. RESULTS: Two
      thousand ninety-six cases of pertussis were admitted to IMPACT centers, 1174
      during the whole-cell vaccine program (WCV-P) and 842 during the acellular
      vaccine program (ACV-P). Pertussis incidence among children <5 years old
      decreased significantly during the ACV-P, causing an increase in the residual
      proportion of cases either too young to be immunized (<2 months old: ACV-P 39%
      versus WCV-P 26.1%; P < 0.0001) or too young for a second dose (2-3 months old:
      42.9% versus 34.2%, respectively; P < 0.0001). A significantly smaller proportion
      of cases (ACV-P 15.1% versus WCV-P 27.3%) occurred in infants who were old enough
      (4-11 months of age) to have received 2 or 3 doses of vaccine. CONCLUSIONS: With
      ACV-P, pertussis hospitalizations in children 4-59 months old decreased in
      frequency, consistent with improved vaccine effectiveness, but remained prominent
      among very young infants. Improved control strategies are needed to reduce
      infections among infants too young for pertussis vaccination.

PMID- 17195703
TI  - Elimination of hepatitis a infection outbreaks in day care and school settings in
      southern Israel after introduction of the national universal toddler hepatitis a
      immunization program.
AB  - BACKGROUND: In 1999, Israel became the first country to begin universal toddler
      immunization against hepatitis A infection with a 2-dose schedule at 18 and 24
      months. The effect of the Israeli program on outbreaks of Hepatitis A in day care
      and school settings was studied. METHODS: The records of all hepatitis A illness
      outbreaks in day care and school settings reported to the Ministry of Health in
      Southern Israel during 1993 through 2005 were reviewed. The number of exposed
      contacts for whom postexposure prophylaxis was administered was retrieved from
      records of epidemiologic investigations. Rates of immunization coverage were
      extracted from records of Maternal and Child Health Clinics. RESULTS: Three
      hundred nineteen cases of hepatitis A illness during the years 1993 through 2005
      were associated with 113 outbreaks in day care and school settings of which 92%
      occurred before the institution of universal toddler immunization. Since 2000, no
      hepatitis A infection outbreaks have been reported in any day care and school
      settings in the region. An average of 732 children received immunoglobulin
      prophylaxis yearly because of exposure to an outbreak in an educational setting
      during the preimmunization period, 106 in 2000 and zero in the 5 years since
      2001. The data showed marked herd immunity since school-aged children born before
      1999 were not immunized, but elimination of outbreaks occurred equally in that
      age group. Immunization coverage was 86.4% for one dose of hepatitis A vaccine by
      age 3 years and 77.3% for 2 doses among the birth cohort of 2000. CONCLUSIONS:
      Universal hepatitis A immunization of toddlers was associated with disappearance
      of outbreaks in educational settings. This included cohorts of nonimmunized
      children representing marked herd immunity.

PMID- 17195704
TI  - Impact of rotavirus infections on outpatient clinic visits in chile.
AB  - BACKGROUND: Incorporation of new rotavirus vaccines into national programs of
      developing countries will rely on well-designed cost-effective analysis based on
      accurate assessment of disease burden. For Chile, rotavirus disease burden is
      determined mostly by outpatient clinic and emergency room visits and by
      hospitalizations. We previously estimated a yearly incidence of 8000 and 53,000
      hospitalizations and emergency room visits respectively for children <or=3 years
      of age. OBJECTIVE: The objective of this study was to quantify the impact of
      rotavirus as a cause of outpatient clinic visits. METHODS: A prospective
      surveillance protocol between the Health Ministry and the University of Chile in
      11 outpatient clinics from 6 regions included reporting of all acute diarrhea
      cases in children <5 years of age and collection of a stool sample for the first
      5 children per week. RESULTS: A total of 5217 acute diarrhea episodes requiring
      an outpatient medical visit for a total assigned population of 41,927 children <5
      years of age were reported from August 1, 2004, to October 30, 2005, in the 11
      clinics. A total of 179 rotavirus positive samples were detected from 1313 stools
      collected for an overall positivity of 13.6% (95% confidence limit: 11.8-15.6%).
      Rotavirus outpatient visits occurred during all 15 months without a clear
      seasonal predominance and peaked between 6 months and 2 years of age. G4 types
      predominated during the 15-month period. CONCLUSIONS: For Chilean children </=3
      years of age, a yearly estimate of 11,658 to 16,305 outpatient medical visits
      need to be added to previous disease burden estimates.

PMID- 17195705
TI  - Prolonged norovirus shedding in infants <or=6 months of age with gastroenteritis.
AB  - BACKGROUND: Noroviruses (NV) are one of the leading causes of gastroenteritis in
      young children; however, the duration of NV shedding in young children is not
      well known. METHODS: Fecal specimens were collected from children with acute
      gastroenteritis at a pediatric clinic during the period from November to December
      2002 and tested for NV by reverse transcription-polymerase chain reaction.
      RESULTS: Of 71 children infected with NV, 60 (84.5%) were less than 3 years old.
      Among children aged <2 years and those aged 2 to 5 years, the duration of illness
      was longer (7 days versus 3.5 days, P = 0.0069), the maximum number of stools in
      a 24-hour period was greater (7 versus 3, P = 0.0078) and a 20-point severity
      score was higher (11 versus 8, P = 0.0031) in patients aged <2 years than in
      patients aged 2 to 5 years. Among the 23 children whose follow-up specimens were
      obtained, the median duration of NV shedding was 16 days (range, 5-47 days).
      Virus shedding for more than 2 weeks after onset was observed in 75% (6 of 8),
      71.4% (5 of 7) and 25% (2 of 8) of children aged <1 year, 1 year and 2 to 3
      years, respectively. Three infants aged <or=6 months continued to excrete NV for
      an extremely long period (more than 42, 44 and 47 days from onset) after
      recovery. CONCLUSION: Long-term virus shedding after the disappearance of
      clinical symptoms was observed. Caution should be exercised when handling the
      excrement of infants and young children infected with NV.

PMID- 17195706
TI  - Mycetoma in children: experience with 15 cases.
AB  - BACKGROUND: Mycetoma is a chronic infection caused by aerobic actinomycetes and
      filamentous fungi. It is an occupational disease frequent in tropical countries
      and is uncommon in children. METHODS: A retrospective (25 years) report of
      mycetomas was conducted in children less than 15 years of age. Each of the cases
      was studied clinically and proven with microbiologic tests: direct examinations
      (to identify and classify the grains), cultures and identification based on
      morphology and biochemical tests. The therapeutic experience of the cases was
      also reviewed. RESULTS: In a 25-year period, a total of 334 mycetomas were seen
      at our institution, 15 of which (4.5%) were in patients 15 years of age and
      younger (mean age: 11.2 years, age range: 6-15 years). Twelve cases were males
      and 3 females. The main clinical location was the foot in 10 of 15 (66.6%).
      Etiologies included 13 actinomycetomas and 2 eumycetomas. Etiologic agents were
      Nocardia brasiliensis in 12 cases, Nocardia asteroides in one and Madurella
      mycetomatis in 2. Eleven of the13 cases of actinomycetomas treated with
      trimethoprim-sulfamethoxazole plus diaminodiphenylsulfone were cured. The 2
      failures were successfully treated with amoxicillin/clavulanate. One of the
      eumycetomas was cured with itraconazole therapy, whereas the other failed various
      treatments eventuating in surgical amputation. CONCLUSIONS: Mycetomas are
      exceptional in children; in our setting, actinomycetomas are more frequent than
      eumycetomas. The clinical and microbiologic diagnosis is simple. Overall,
      treatment response is better for actinomycetomas than for eumycetomas.

PMID- 17195707
TI  - Endocrine abnormalities and impaired growth in human immunodeficiency virus
      infected children.
AB  - OBJECTIVES: Identify endocrine differences between human immunodeficiency virus-
      (HIV) infected versus uninfected children and evaluate associations of growth and
      body composition with endocrine measures. STUDY DESIGN: Nested case-control study
      in 21 HIV-infected and 46 age- and sex-matched uninfected children in the Women
      and Infant Transmission Study. Plasma specimens from children between 2.5 to 7.0
      years of age, taken during 3-4 visits, were tested for insulin-like growth factor
      binding protein-3 (IGFBP-3), cortisol, dehydroepiandrosterone (DHEA), growth
      hormone and thyroid studies. Longitudinal mixed and generalized estimating
      equation models compared group means and examined effects of endocrine measures
      on growth and body composition, respectively. RESULTS: HIV-infected children had
      lower IGFBP-3 than uninfected children (1.96 +/- 0.09 mg/L versus 2.34 +/- 0.06
      mg/L, P < 0.001). In infected but not in uninfected children, IGFBP-3 values and
      DHEA:cortisol ratios were associated with weight- and body mass index-for-age z
      scores ([WAZ] P = 0.019, <.001 respectively, and [BMZ] P = 0.029, 0.038). DHEA
      concentration was associated with height-for-age z score (P = 0.049).
      CONCLUSIONS: In these HIV-infected children compared with their uninfected
      counterparts, IGFBP-3 concentration was different between groups. Infected
      children had multiple endocrine associations with growth and body composition not
      found in their uninfected peers. We hypothesize that in HIV-infected children,
      growth hormone resistance and shunting of precursors from adrenal androgen to
      cortisol production contributes to altered body composition and stunting.

PMID- 17195708
TI  - Patient, caregiver and regimen characteristics associated with adherence to
      highly active antiretroviral therapy among HIV-infected children and adolescents.
AB  - BACKGROUND: This study assesses the relationship between child and caregiver
      perceptions of medication responsibility, disease knowledge, regimen complexity
      and adherence to highly active antiretroviral therapy among HIV-positive
      children. We also examine the association of adherence to child and caregiver
      demographic characteristics and surrogate markers of HIV disease. METHODS: For
      this 6-month longitudinal study, 24 HIV-positive children (mean age = 14.0 years)
      being treated with highly active antiretroviral therapy and their caregivers
      completed measures of medication responsibility and disease knowledge. Medication
      Event Monitoring System caps calculated adherence across months 1 through 3 (time
      1) and 4 through 6 (time 2). RESULTS: Medication Event Monitoring System data
      revealed adherence rates of 81% at time 1 and 79% at time 2. Only 8% (n = 2) of
      child-caregiver pairs reported complete agreement regarding who held
      responsibility for medication-related tasks. Patients' responsibility for
      medication was correlated with age based on child (r = .51) and caregiver (r =
      .57; Ps < 0.05) perceptions, although their regimen knowledge was not. Greater
      regimen knowledge among caregivers and fewer child-caregiver discrepancies about
      medication responsibility predicted better adherence (adjusted R = .45). Finally,
      adherence was correlated with CD4 percentages at time 1 (r = .50) and viral load
      at time 1 (r = -.56) and time 2 (r= -.68; Ps < 0.05). CONCLUSIONS: Medication
      adherence among HIV-infected children is lower than required for optimal viral
      suppression. Adherence is related to surrogate markers of HIV disease but not to
      child or caregiver demographic variables. Responsibilities for medication-related
      tasks should be clarified among family members, regimen knowledge should be
      emphasized and caregivers should avoid assigning treatment responsibility to a
      child prematurely.

PMID- 17195709
TI  - Severe acute respiratory syndrome in children.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is a febrile, respiratory
      tract illness caused by infection with the newly identified SARS-associated
      coronavirus. A notable feature of the 2003 global SARS outbreak was the relative
      paucity of cases reported among children. We reviewed the epidemiologic and
      clinical features of SARS in children and discuss implications of these findings
      for diagnosis, treatment and prevention of SARS. METHODS: We performed a
      literature search to identify reports of pediatric (younger than 18 years of age)
      patients meeting the World Health Organization case definitions for SARS and
      abstracted relevant clinical and epidemiologic information. RESULTS: We
      identified 6 case series reporting 135 pediatric SARS patients (80 laboratory
      confirmed, 27 probable and 28 suspect) from Canada, Hong Kong, Taiwan and
      Singapore. Among laboratory-confirmed and probable SARS cases, the most common
      symptoms included fever (98%), cough (60%) and nausea or vomiting (41%); 97% had
      radiographic abnormalities. The clinical presentation of SARS in patients older
      than 12 years of age was similar to that in adults. However, patients 12 years of
      age or younger had milder disease and were less likely than older children to be
      admitted to an intensive care unit, receive supplemental oxygen or be treated
      with methylprednisolone. No deaths were reported among children or adolescents
      with SARS, and at 6 months after illness only mild residual changes were reported
      in exercise tolerance and pulmonary function. There is only 1 published report of
      transmission of SARS virus from a pediatric patient. CONCLUSIONS: Children and
      adolescents are susceptible to SARS-associated coronavirus infection, although
      the clinical course and outcome are more favorable in children younger than 12
      years of age compared with adolescents and adults. Transmission of SARS from
      pediatric patients appears to be uncommon but is possible.

PMID- 17195710
TI  - Anti-inflammatory properties of macrolides.

PMID- 17195711
TI  - Tigecycline: a single antibiotic for polymicrobial infections.

PMID- 17195713
TI  - Pneumocystis is not a direct cause of sudden infant death syndrome.
AB  - We compared the frequency of Pneumocystis in 126 sudden infant death syndrome
      (SIDS) cases with a control group of 24 infants from the San Diego SIDS/SUDC
      Research Project who died of accidental or inflicted injuries. Cysts were
      identified in 33% of SIDS cases and 29% of controls. We conclude that
      Pneumocystis is not a direct cause of SIDS.

PMID- 17195712
TI  - Is pertussis immune globulin efficacious for the treatment of hospitalized
      infants with pertussis? No answer yet.
AB  - In a multicenter, randomized, placebo-controlled clinical trial of pertussis
      immune globulin, intravenous (P-IGIV), 25 infants hospitalized with pertussis
      were enrolled in 24 months (15% of the target sample size) before the study was
      prematurely terminated because of expiration of the P-IGIV lots and
      unavailability of additional study product. Although well tolerated, there was no
      difference in the number or rate of improvement of symptoms (paroxysmal cough,
      whoop, apnea, bradycardia, oxygen desaturations) in P-IGIV recipients compared
      with placebo.

PMID- 17195714
TI  - Cerebral tuberculoma presenting as flexion spasms.
AB  - A 10-month-old girl was admitted with refractory infantile spasms. Video EEG
      demonstrated focal epileptic activity, and MRI revealed a conglomeration of
      annular lesions. Surgical excision was performed and pathology was consistent
      with tuberculoma. After antituberculous therapy, the outcome was favorable.
      Despite all investigations, Mycobacterium tuberculosis's mode of transmission was
      unclear, and both congenital and postnatal acquired forms were considered.

PMID- 17195715
TI  - Inguinal lymphadenitis caused by mycobacterium haemophilum in an immunocompetent
      child.
AB  - Infections caused by Mycobacterium haemophilum in immunocompetent patients are
      unusual. M. haemophilum have been associated with cervicofacial lymphadenitis in
      children, but inguinal infections have not yet been described. We present a case
      of an inguinal lymphadenitis caused by M. haemophilum in an immunocompetent girl.

PMID- 17195716
TI  - Efficacy and plasma concentrations of indinavir when boosted with ritonavir in
      human immunodeficiency virus-infected Thai children.
AB  - We evaluated 19 children using 220-300 mg/m of indinavir (IDV) boosted with 100
      mg ritonavir (RTV) (n = 12) or full-dose RTV (n = 7). Geometric mean (GM) (90%
      confidence interval, CI) of IDV Ctrough in children who took IDV with 100 mg RTV
      (n = 12) was 0.17 (0.06-0.50) mg/L. For children who took IDV with full-dosage
      RTV, GM (90% CI) was 0.40 (0.10-1.61) mg/L. C2hours were less than 10 mg/L in all
      subjects. Eighteen children had good virologic response. This report demonstrates
      that smaller IDV dosages given with RTV provide efficacious plasma concentrations
      and can be safely used.

PMID- 17195717
TI  - Treatment of Dientamoeba fragilis infection with paromomycin.
AB  - Treatment with paromomycin (25-35 mg/kg/d for 7 days) was evaluated prospectively
      in 15 children with Dientamoeba fragilis infection after 1-month follow-up. At
      the end of the study, parasitologic effectiveness and clinical improvement were
      observed in 12/15 (80%) and 13/15 (87%) patients, respectively. Paromomycin
      appears to be an effective drug for treatment of D. fragilis infection in
      children.

PMID- 17195718
TI  - Unsuspected central nervous system lesions in a small child.

PMID- 17195719
TI  - Visual evoked responses in children with tuberculosis treated with ethambutol.

PMID- 17195720
TI  - Brucellosis of the sternum and olecranon in an adolescent.

PMID- 17195721
TI  - Cmap ADHD and comorbid aggression algorithm.

PMID- 17195723
TI  - Improvement in speech dysfluency in Tourette's disorder after tongue piercing.

PMID- 17195724
TI  - Longitudinal development of antisocial behaviors in young and early adolescent
      Puerto Rican children at two sites.
AB  - OBJECTIVE: This report provides descriptive longitudinal findings over three
      waves of a study designed to assess the development of antisocial behaviors in
      young and early adolescent Puerto Rican children at two sites. METHOD: Through
      the use of standard assessment measures, representative samples of Puerto Rican
      children of both genders 5 to 13 years of age and their adult caretakers were
      interviewed at two sites: the South Bronx in New York City (n = 1,138) and the
      Standard Metropolitan Areas in Puerto Rico (n = 1,353; N = 2,491). RESULTS:
      Although no differences in prevalence between the two sites were apparent at
      baseline, analyses of the longitudinal data show that site differences emerge
      over time, with a decrease in risk of antisocial behavior over time in the
      Standard Metropolitan Areas relative to the Bronx. CONCLUSIONS: The decreased
      risk of these disorders in the Standard Metropolitan Areas corroborates the low
      rates in Puerto Rico reported in previous research. Future analyses of these data
      are needed to identify the risk and protective factors associated with this
      difference.

PMID- 17195725
TI  - Predicting school dropout and adolescent sexual behavior in offspring of
      depressed and nondepressed mothers.
AB  - OBJECTIVE: To examine predictors of school dropout and adolescent sexual behavior
      in offspring of depressed and nondepressed mothers. Possible moderators of the
      relation between maternal depression and these outcomes also were explored.
      METHOD: Participants were 240 mothers and adolescents assessed annually from 6th
      through 12th grade. Interviews and questionnaires measured the chronicity and
      severity of the mother's depressive episodes, the mother's educational
      attainment, socioeconomic status, the presence of a father, the adolescent's IQ,
      externalizing behaviors, and substance use disorders. RESULTS: Substance use
      disorders before ninth grade significantly predicted higher rates of both school
      dropout and adolescent sexual behavior. Lower levels of mother's educational
      attainment and higher rates of adolescent's externalizing behaviors in grades 6
      through 8 predicted higher school dropout. Higher IQ was associated with a lower
      likelihood of dropping out among offspring of never or moderately depressed
      mothers, but not for offspring of chronic/severely depressed mothers. Among
      offspring of never or moderately depressed mothers, the presence of a male head
      of household was associated with lower rates of adolescent sexual behavior, but
      not among offspring of chronically/severely depressed mothers. CONCLUSIONS: These
      findings have implications for the development of programs aimed at preventing
      behavior problems in high-risk adolescents.

PMID- 17195726
TI  - Reading problems, psychiatric disorders, and functional impairment from mid- to
      late adolescence.
AB  - OBJECTIVE: To examine psychiatric morbidity and functional impairment of
      adolescents with and without poor reading skills during mid- to late adolescence.
      METHOD: The sample consisted of 188 adolescents, 94 with poor reading skills and
      94 with typical reading skills, screened from a larger sample in the public
      schools at age 15. To assess psychiatric disorders, participants were assessed
      annually with the Schedule for Affective Disorders and Schizophrenia for School
      Age Children-Epidemiologic Version (up to 4.5 years; maximum age, 20 years).
      Functional impairment was assessed with the Child and Adolescent Functional
      Assessment Scale. RESULTS: Adolescents with poor reading skills evidenced higher
      rates of current attention-deficit/hyperactivity, affective, and anxiety
      disorders, particularly social phobia and generalized anxiety disorder. Anxiety
      disorders but not affective disorders were related to reading status after
      controlling for attention-deficit/hyperactivity disorder. Adolescents with poor
      reading evidenced more functional impairment across multiple areas than youths
      with typical reading skills, even after considering the presence of comorbid
      attention-deficit/hyperactivity disorder. CONCLUSIONS: The increased psychiatric
      morbidity and functional impairment of adolescents with reading problems
      highlight the importance of developing interventions that help these youths
      address reading deficits and associated vulnerabilities during the last years of
      secondary school.

PMID- 17195727
TI  - Preventive effects of treatment of disruptive behavior disorder in middle
      childhood on substance use and delinquent behavior.
AB  - OBJECTIVE: Disruptive behavior disorder (DBD) is a well-known risk factor for
      substance abuse and delinquent behavior in adolescence. Therefore, the long-term
      preventive effects of treatment of DBD in middle childhood on beginning substance
      use and delinquency in early adolescence were investigated. METHOD: Children with
      DBD (8-13 years old) had been randomly assigned to manualized behavior therapy
      (Utrecht Coping Power Program; UCPP) or to care as usual (CU) in the Netherlands.
      Five years (2003-2005) after the start of treatment (1996-1999), substance use
      and delinquency were monitored in 61 of the initial 77 adolescents and compared
      with a matched healthy control group by means of self-report questionnaires. One
      factor analyses of variance and Pearson's chi2 analyses were performed. RESULTS:
      Differences in substance use were revealed in favor of the UCPP, with more
      adolescents in the CU group smoking cigarettes in the last month (UCPP 17%, CU
      42%; chi2 = 4.7; p < .03) and more adolescents in the CU group having ever used
      marijuana (UCPP 13%, CU 35%; chi2 = 4.0; p < .045). Moreover, in this respect,
      the UCPP fit in the range of the matched healthy control group. Both treatment
      groups were comparable to the matched healthy control group in delinquent
      behavior. CONCLUSIONS: Manualized behavior therapy for DBD in middle childhood
      seems to be more powerful than CU in reducing substance use in early adolescence.
      Both treatment conditions show a beneficial long-term preventive effect on
      delinquency.

PMID- 17195729
TI  - Online health promotion, early identification of difficulties, and help seeking
      in young people.
AB  - OBJECTIVE: To examine the use and impact of a dedicated health information Web
      site for adolescents. METHOD: Five hundred fifty-eight (27.2%) of all students in
      grades 7 through 12 from 4 schools logged onto the Web site; 1775 (86.4%) of all
      students in these grades completed a year-end health survey, with 455 (81.5%) of
      the students who used the Web site completing the survey. Dependent variables
      were help seeking and satisfaction ratings plus visits to specific Web site
      sections. Predictor variables were demographic characteristics, mental health,
      and psychosocial difficulties assessed at years' end. RESULTS: Students logged on
      >11,000 times during the year. Female students, students wanting professional
      help, those scoring higher on depressive vulnerability measures, and students
      reporting more severe mood problems were related to logging on frequently over
      longer periods of time, as well as viewing information sheets, posting and
      viewing questions and answers, and completing the symptom screen. Students
      accessing the Web site from 1 to 7 A.M. reported higher levels of distress than
      did students who accessed the Web site at other times of the day. Visits to the
      Web site were positively associated with visits to school health centers and
      guidance counselors and referrals to a health professional. CONCLUSIONS: Results
      are consistent with a health-needs model of utilization of this Internet-based
      health resource. A school-based health information Web site holds significant
      promise for health promotion and early self-identification for emotional
      problems.

PMID- 17195728
TI  - Bullying, depression, and suicidality in adolescents.
AB  - OBJECTIVE: To assess the association between bullying behavior and depression,
      suicidal ideation, and suicide attempts among adolescents. METHOD: A self-report
      survey was completed by 9th- through 12th-grade students (n = 2342) in six New
      York State high schools from 2002 through 2004. Regression analyses were
      conducted to examine the association between being victimized and bullying others
      with depression, ideation, and attempts. RESULTS: Approximately 9% of the sample
      reported being victimized frequently, and 13% reported bullying others
      frequently. Frequent exposure to victimization or bullying others was related to
      high risks of depression, ideation, and suicide attempts compared with
      adolescents not involved in bullying behavior. Infrequent involvement in bullying
      behavior also was related to increased risk of depression and suicidality,
      particularly among girls. The findings indicate that both victims and bullies are
      at high risk and that the most troubled adolescents are those who are both
      victims and bullies. Psychopathology was associated with bullying behavior both
      in and away from school. CONCLUSIONS: Victimization and bullying are potential
      risk factors for adolescent depression and suicidality. In evaluations of
      students involved in bullying behavior, it is important to assess depression and
      suicidality.

PMID- 17195730
TI  - Child and adolescent psychiatrists' practices in assisting their adolescent
      patients who smoke to quit smoking.
AB  - OBJECTIVE: This national study examined the practices and perceptions of smoking
      cessation activities among child and adolescent psychiatrists. METHOD: A random
      sample of child and adolescent psychiatrists was identified from the membership
      list of the American Academy of Child and Adolescent Psychiatry and was mailed a
      valid and reliable 34-item questionnaire. RESULTS: A total of 184 responses (47%)
      were received. A plurality (48%) of psychiatrists reported being self-taught in
      smoking cessation techniques. A majority (67%) of psychiatrists were in the
      maintenance stage for asking about smoking status. However, only 19% consistently
      made attempts to assess willingness to quit, and 30% consistently gave messages
      urging the smoker to quit. The perceived number of barriers for addressing
      smoking was negatively correlated with psychiatrists' levels of confidence (r = 
      0.35, p <.001) and preparedness (r = -0.39, p <.001) in addressing smoking
      cessation. Estimations by the psychiatrists of youths who smoked were 61% of
      those with conduct disorders, 46% of those with schizophrenia, and 40% of those
      with attention-deficit/hyperactivity disorder. CONCLUSION: Considering the
      perceived high rate of patient smoking and the lack of formal training in smoking
      cessation, more postgraduate education is needed to adequately prepare child and
      adolescent psychiatrists for addressing tobacco cessation.

PMID- 17195731
TI  - Conversion disorder in Australian pediatric practice.
AB  - OBJECTIVES: To describe the incidence and clinical features of children
      presenting to Australian child health specialists with conversion disorder.
      METHOD: Active, national surveillance of conversion disorder in children younger
      than 16 years of age during 2002 and 2003. RESULTS: A total of 194 children were
      reported on. The average age was 11.8 years; 23% were younger than 10 years of
      age. Presentations were complex, with 55% presenting with multiple conversion
      symptoms. The most common presentations were disturbance of voluntary motor
      function (64%), sensory symptoms (24%), pseudoseizure (23%), and respiratory
      problems (14%). Hospital admission was required for 70%, with an average stay of
      10.2 days. Antecedent stressors were also reported in 62% and a history of mental
      health concerns in 42%, with 14% of children taking psychotropic medications for
      comorbid anxiety or depression. The incidence of conversion disorder in
      Australian specialist child health practice is estimated to be between 2.3 and
      4.2/100,000. CONCLUSIONS: Conversion disorder is associated with a significant
      burden for the child, family, and the health system. This study emphasizes the
      comorbidity with anxiety, depression, and symptoms of pain and fatigue. It also
      highlights the potential impact of "commonplace" stressors such as family
      conflict and children's loss of attachment figures.

PMID- 17195732
TI  - Psychiatric adjustment in the year after meningococcal disease in childhood.
AB  - OBJECTIVE: To assess psychiatric status after meningococcal disease. METHOD:
      Cohort study of 66 children (34 boys, 32 girls) ages 4 to 17 years admitted to
      pediatric hospitals with meningococcal disease. The main outcome measure was
      psychiatric disorder (1-year period and point prevalence on the Schedule for
      Affective Disorders and Schizophrenia for School-Age Children interview for
      children 6 years or older; point prevalence in younger children on the Behavior
      Screening Questionnaire). RESULTS: During the course of the year after discharge
      from hospital, psychiatric disorders were identified in 23 of 40 (57%) children
      ages 6 years or older. The most common primary disorders were depressive,
      oppositional defiant, and anxiety disorders. At the time of 12-month follow-up,
      psychiatric disorders were present in 13 of 40 (32%) of those ages 6 or older and
      in 7 of 26 (26%) under 6 years old. Two children had a diagnosis of posttraumatic
      stress disorder. Logistic regression analysis showed that global meningococcal
      illness severity score, clinical shock on admission, and impairing premorbid
      emotional and behavioral problems in the child were independent predictors of
      psychiatric disorder at 12-month follow-up. CONCLUSIONS: Psychiatric disorders
      are common in the year after meningococcal disease. Especially at risk are
      children who are severely medically ill and those with more impairing premorbid
      emotional and behavioral problems.

PMID- 17195733
TI  - Attention problems and attention-deficit/hyperactivity disorder in discordant and
      concordant monozygotic twins: evidence of environmental mediators.
AB  - OBJECTIVE: To study familial and nonfamilial environmental influences on
      attention problems and attention-deficit/hyperactivity disorder (ADHD) in
      monozygotic twins discordant and concordant-high and low for these traits.
      METHOD: Ninety-five twin pairs from The Netherlands Twin Register were selected.
      Longitudinal survey data were collected at 1, 2, 3, 5, 7, 10, and 12 years from
      parents, twins, and teachers. Mothers participated in a structured clinical
      interview when twins were between 10 and 17 years of age. RESULTS: Affected twins
      from discordant pairs scored higher than unaffected cotwins on multiple measures
      of attention problems, ADHD, and other behavior problems according to mother,
      teacher, and self. Behavioral discordance was evident at age 2 and all subsequent
      measurements. Compared with unaffected cotwins, affected twins had lower birth
      weight and delayed physical growth and motor development. Differences between
      discordant and concordant groups were reported for maternal smoking, sleeping in
      different rooms, and living with only one parent. CONCLUSIONS: Significant
      markers of ADHD are found in infancy and include low birth weight and delayed
      motor development. As the knowledge of specific genetic and environmental
      influences on ADHD increases, future studies may focus on their complex
      interplay.

PMID- 17195734
TI  - Source-specific oppositional defiant disorder: comorbidity and risk factors in
      referred elementary schoolboys.
AB  - OBJECTIVE: To examine differences in risk factors and comorbid conditions for
      oppositional defiant disorder (ODD) symptom groups in a sample of 248 elementary
      schoolboys (ages 6-10) recruited from 1994 to 1996. METHOD: The boys and their
      mothers received multiple assessments of cognitive, behavioral, academic, and
      family functioning, including a clinic-based evaluation in Stony Brook, NY. ODD
      was defined using four different strategies for aggregating data from mother and
      teacher reports of DSM-IV symptoms. RESULTS: Source-specific ODD symptom groups
      had better internal validity and were more differentiated than groups defined
      using the other strategies. The mother-defined ODD symptom group (ODD/M) had
      higher levels of maternal detachment than the teacher-defined symptom group
      (ODD/T), and the ODD/T group had more social problems than the ODD/M group. The
      classification agreement group (ODD/M + T) evidenced higher levels of sensation
      seeking, maternal control, and comorbid symptoms than the ODD/M and ODD/T groups.
      Controlling for co-occurring attention-deficit/hyperactivity disorder and conduct
      disorder symptoms altered some of the relationships among ODD, comorbid symptoms,
      and psychosocial correlates. CONCLUSIONS: Patterns of co-occurring psychiatric
      symptoms and psychosocial correlates of ODD symptom groups varied depending on
      the rater(s) used to determine group membership. Results support continued
      research into source specificity for conceptualizing ODD.

PMID- 17195735
TI  - Practice parameter for the assessment and treatment of children and adolescents
      with bipolar disorder.
AB  - This practice parameter reviews the literature on the assessment and treatment of
      children and adolescents with bipolar disorder. The parameter focuses primarily
      on bipolar 1 disorder because that is the type most often studied in juveniles.
      The presentation of bipolar disorder in youth, especially children, is often
      considered atypical compared with that of the classic adult disorder, which is
      characterized by distinct phases of mania and depression. Children who receive a
      diagnosis of bipolar disorder in community settings typically present with rapid
      fluctuations in mood and behavior, often associated with comorbid attention
      deficit/hyperactivity disorder and disruptive behavior disorders. Thus, at this
      time it is not clear whether the atypical forms of juvenile mania and the classic
      adult form of the disorder represent the same illness. The question of diagnostic
      continuity has important treatment and prognostic implications. Although more
      controlled trials are needed, mood stabilizers and atypical antipsychotic agents
      are generally considered the first line of treatment. Although patients may
      respond to monotherapy, combination pharmacotherapy is necessary for some youth.
      Behavioral and psychosocial therapies are also generally indicated for juvenile
      mania to address disruptive behavior problems and the impact of the illness on
      family and community functioning.

PMID- 17195736
TI  - Practice parameter for the assessment and treatment of children and adolescents
      with oppositional defiant disorder.
AB  - Oppositional defiant disorder (ODD) is a common clinical problem in children and
      adolescents. Oppositionality and associated types of aggressive behavior are
      among the most common referral problems in child psychiatry. Grouped among the
      disruptive behavior disorders, ODD is frequently comorbid with other psychiatric
      conditions and often precedes the development of conduct disorder (CD), substance
      abuse, and severely delinquent behavior. Youth with ODD may also have specific CD
      behaviors, such as aggression. Although compared with CD there exists a smaller
      and less sophisticated empirical database for ODD, this parameter draws upon the
      existing ODD and CD literature to make recommendations regarding diagnosis and
      treatment of ODD. The etiology of ODD is complex and its development is based on
      a cumulative risk/protective factor model that combines biological,
      psychological, and social factors. Recommended treatment is multimodal and
      extensive, involving individual and family psychotherapeutic approaches,
      medication, and sociotherapy. Methodologically sound controlled clinical trials
      are lacking.

PMID- 17195738
TI  - Discontinuation of antiretroviral therapy postpartum: no evidence for altered
      viral set point.

PMID- 17195739
TI  - Predictive factors of hyperhomocysteinemia in HIV-positive patients.

PMID- 17195741
TI  - Electrode independence in intraneural cochlear nerve stimulation.
AB  - OBJECTIVES/HYPOTHESIS: We have previously reported feline electrophysiological
      and anatomical studies focused on the development of an intraneural auditory
      neuroprosthesis. Because only the tips of the electrodes implanted in the
      cochlear nerve are the stimulating elements that abut the nerve axons, we
      hypothesize that intraneural stimulation will be highly focal in nature. In this
      article, we report the electrophysiological characterization of the selective
      activation of subpopulations of cochlear nerve fibers via electrodes implanted in
      feline cochlear nerve. STUDY DESIGN: We have used a forward-masking paradigm to
      estimate the extent of stimulation overlap produced by pairs of electrodes
      implanted into the cochlear nerve. METHODS: The technique uses sequential
      stimulation via masking and probe electrodes and monitoring of the electrically
      evoked auditory brain stem response as an index of cochlear nerve fiber
      recruitment. We investigated overlap in all possible electrode pair combinations.
      RESULTS AND CONCLUSION: Many electrode pairs manifest virtually no overlap in the
      subpopulations of fibers excited by perithreshold stimuli, whereas most had
      considerable overlap at higher stimulation levels. However, we also noted that
      our measured overlap was similar across electrodes possibly because of lack of
      specificity of the whole nerve electrically evoked auditory brain stem response
      as an assay for this parameter. These findings indicate that direct cochlear
      nerve stimulation via intraneural electrodes provides selective excitation of
      small subpopulations of cochlear nerve fibers, and suggest that cochlear nerve
      stimulation may selectively evoke narrow-band frequency percepts.

PMID- 17195742
TI  - Implication of central asymmetry in speech processing on selecting the ear for
      cochlear implantation.
AB  - OBJECTIVE: Emerging evidence in auditory neuroscience suggests that central
      auditory pathways process speech asymmetrically. In concert with left cortical
      specialization for speech, a "right-ear advantage" in speech perception has been
      identified. The purpose of this study is to determine if this central asymmetry
      in speech processing has implications for selecting the ear for cochlear
      implantation. STUDY DESIGN: Retrospective cohort study. SETTING: Academic
      university medical center PATIENTS: One hundred one adults with bilateral severe
      to-profound sensorineural hearing loss INTERVENTION: Cochlear implantation with
      the Nucleus 24 Contour device. MAIN OUTCOME MEASUREMENTS: Patients were divided
      into two groups according to the ear implanted. Results were compared between
      left-ear- and right-ear-implanted patients. Further subgroup analysis was
      undertaken, limited to right-handed patients. Postoperative improvement on
      audiograms and scores on speech perception tests (Hearing in Noise test, City
      University of New York in quiet and in noise test, Consonant-Vowel Nucleus-
      Consonant words, and phonemes) at 1 year was compared between groups. Analysis of
      covariance was used to control for any intergroup differences in preoperative
      characteristics. RESULTS: The groups were matched in age, duration of hearing
      loss, duration of hearing aid use, percentage implanted in the better hearing
      ear, and preoperative audiologic testing. Postoperatively, there were no
      differences between left-ear- and right-ear-implanted patients in improvement on
      speech recognition tests. CONCLUSION: Despite central asymmetry in speech
      processing, our data do not support a right-ear advantage in speech perception
      outcomes with cochlear implantation. Therefore, among the many factors in
      choosing the ear for cochlear implantation, central asymmetry in speech
      processing does not seem to be a contributor to postoperative speech recognition
      outcomes.

PMID- 17195743
TI  - Auditory midbrain implant: a combined approach for vestibular schwannoma surgery
      and device implantation.
AB  - HYPOTHESIS: The lateral suboccipital approach is a well-established route for
      safe removal of vestibular schwannomas in neurofibromatosis Type 2 (NF2)
      patients. The goal of this study was to assess if this approach can be extended
      to a lateral supracerebellar infratentorial approach to enable insertion of an
      auditory midbrain implant (AMI) penetrating array along the tonotopic gradient of
      the inferior colliculus central nucleus (ICC). BACKGROUND: The AMI is a new
      auditory prosthesis designed for penetrating stimulation of the ICC in patients
      with neural deafness. The initial candidates are NF2 patients who, because of the
      growth and/or surgical removal of bilateral acoustic neuromas, develop neural
      deafness and are unable to benefit from cochlear implants. The ideal surgical
      approach in NF2 patients must first enable safe removal of vestibular schwannomas
      and then provide sufficient exposure of the midbrain for AMI implantation.
      METHODS: This study was performed on formalin-fixed and fresh cadaver specimens.
      Computed tomography scan and magnetic resonance imaging were used to study the
      heads of the specimens and for surgical navigation. RESULTS: The lateral
      suboccipital craniotomy enabled sufficient exposure of the cerebellopontine angle
      and internal auditory canal for tumor removal. It could then be extended to a
      lateral supracerebellar infratentorial approach that provided good exposure of
      the dorsolateral aspect of the tentorial hiatus and mesencephalon for
      implantation of the AMI along the tonotopic gradient of the ICC. This approach
      did not endanger the trochlear nerve or any major midline venous structures in
      the quadrigeminal cistern. CONCLUSION: This modified lateral suboccipital
      approach ensures safe removal of large vestibular schwannomas and provides
      sufficient exposure of the inferior colliculus for ideal AMI implantation.

PMID- 17195744
TI  - The first successful case of hearing produced by electrical stimulation of the
      human midbrain.
AB  - HYPOTHESIS: Electrical stimulation of the inferior colliculus in the midbrain can
      provide a safe and efficacious alternative to auditory brainstem implants (ABIs).
      BACKGROUND: Patients with neurofibromatosis type 2 (NF2) receive limited speech
      recognition with ABIs. Some ABI patients without NF2 can achieve excellent speech
      understanding, suggesting that the limited NF2 performance is due to brainstem
      damage from the tumor and its removal. METHODS: An array of electrodes (Med-El
      ABI) was placed on the dorsal surface of the inferior colliculus in the midbrain
      of a human volunteer as an auditory prosthesis via an infratentorial
      supracerebellar median surgical approach. Electrophysiological responses,
      psychophysical responses, and speech recognition were measured. RESULTS:
      Electrical stimulation produced auditory sensations on all 12 electrodes with no
      nonauditory sensations. Auditory threshold levels indicated the stability of the
      electrode array over time. Electrophysiological measures showed activation in the
      contralateral auditory cortex but none in ipsilateral cortex. All electrodes
      demonstrated a full range of loudness sensation and electrode-specific pitch
      sensations. Speech recognition was significant, but limited in the first month
      after surgery. CONCLUSION: This approach may provide advantages for patients with
      brainstem damage.

PMID- 17195745
TI  - Influence of chronic middle ear diseases on gustatory function: an
      electrogustometric study.
AB  - OBJECTIVE: We aimed to quantitatively determine whether middle ear inflammation
      associated with unilateral chronic otitis media (COM), cholesteatoma, or
      otosclerosis affects gustatory function. STUDY DESIGN: Prospective study.
      SETTING: University Hospital, Department of Otolaryngology. PATIENTS: Forty-two
      patients had unilateral COM (22 men, 20 women; mean age, 54.2 yr), 57 had
      unilateral cholesteatoma (35 men, 22 women; mean age, 42.1 yr), and 19 had
      unilateral otosclerosis (10 men, 9 women; mean age, 49.3 yr). MAIN OUTCOME
      MEASURES: Patients underwent taste testing using electrogustometry (EGM) and
      sensation thresholds were compared in the affected and unaffected ears among
      groups and between affected and unaffected ears in each group. RESULTS: Patients
      with COM and cholesteatoma exhibited an increase in taste threshold in the
      affected ears compared to the unaffected ears (p < 0.05), whereas otosclerosis
      patients did not. The extent of the increase of the sensation thresholds in the
      affected ears was very similar between patients with COM and those with
      cholesteatoma (p = 0.548). CONCLUSION: Our EGM study showed that cholesteatoma
      and chronic middle ear inflammation affected gustatory function to a similar
      degree.

PMID- 17195746
TI  - Sigmoid sinus diverticulum: a new surgical approach to the correction of
      pulsatile tinnitus.
AB  - OBJECTIVE: Tinnitus represents a bothersome symptom not infrequently encountered
      in an otology practice. Tinnitus can be the harbinger of identifiable middle or
      inner ear abnormality; but more frequently, tinnitus stands alone as a subjective
      symptom with no easy treatment. When a patient complains of tinnitus that is
      pulsatile in nature, a thorough workup is indicated to rule out vascular
      abnormality. We report of a new diagnostic finding and method of surgical
      correction for select patients with pulsatile tinnitus. STUDY DESIGN:
      Retrospective case series. SETTING: Tertiary care, academic referral center.
      PATIENTS: Among patients seen for complaints of unilateral or bilateral pulsatile
      tinnitus, five were identified with diverticula of the sigmoid sinus. All
      patients had normal in-office otoscopic, tympanometric, and audiometric
      evaluations. Patients with paragangliomas or benign intracranial hypertension
      were excluded. Auscultation of the pinna or mastoid revealed an audible bruit in
      most patients. All patients underwent computed tomographic angiography of the
      temporal bone. In all cases, this finding was on the side coincident with the
      tinnitus. INTERVENTION: Three of five patients underwent transmastoid
      reconstruction of the sigmoid sinus. MAIN OUTCOME MEASURE: Patients were
      evaluated clinically for presence or absence of pulsatile tinnitus after
      reconstructive surgery. RESULTS: All patients electing surgical reconstruction
      had immediate and lasting resolution of the tinnitus. CONCLUSION: Surgical
      reconstruction can provide lasting symptom relief for patients with pulsatile
      tinnitus and computed tomographic evidence of a sigmoid sinus diverticulum.

PMID- 17195747
TI  - Congenital aural atresia: review of short- and long-term surgical results.
AB  - OBJECTIVES/HYPOTHESIS: To review the short- (<1 yr) and long-term (>1 yr)
      surgical and hearing outcomes for congenital aural atresia and to analyze the
      stability of surgical results over time. STUDY DESIGN: Retrospective chart review
      of 45 patients (54 ears) who underwent surgery for congenital aural atresia
      during a 5-year period at a tertiary care institution. METHODS: Preoperative and
      postoperative speech reception thresholds, air-bone gaps (ABGs), and pure-tone
      averages were compared and further analyzed for outcome stability over time. The
      complication rate was reviewed and compared with results from similar studies.
      RESULTS: Approximately 50% of patients achieved a speech reception threshold of
      30 dB or better both in the short and long term. The average improvement in ABG
      was 22 dB, resulting in a postoperative ABG of 30 dB or less in three of four
      patients. Short- and long-term outcomes were not significantly different.
      Patients with an intact ossicular chain did not seem to have a significant
      advantage in hearing when compared with patients with a prosthetic reconstruction
      prosthesis. We report a low incidence of meatal stenosis compared with other
      similar reviews and describe surgical modifications that may attribute to this
      outcome. CONCLUSION: Overall, the mean hearing outcome for this group
      collectively did not significantly degrade over time and compared favorably with
      other series. However, there was significant variability among individual
      patients. The safety of this procedure and the demonstrated hearing improvement
      makes it a reasonable option in patients with congenital aural atresia with
      favorable anatomy.

PMID- 17195748
TI  - Prognostic factors in ossiculoplasty.
AB  - OBJECTIVE: To analyze predictive factors of outcome after ossiculoplasty using a
      standard ossicular prosthesis system. STUDY DESIGN: Retrospective review of 140
      ossiculoplasties, performed by the same senior surgeon, with titanium prostheses.
      SETTINGS: Academic hospital and tertiary referral center. PATIENTS: All patients
      undergoing ossiculoplasty with Spiggle and Theis or Kurz titanium total and
      partial prostheses. Documented, postoperative follow-up had to be provided. A
      total of 129 patients (140 ears; 53 men and 76 women) were evaluated.
      INTERVENTIONS: These included ossiculoplasties using 75 Spiggle and Theis
      prostheses (30 partial and 45 total) and 65 Kurz prostheses (35 partial and 30
      total). MAIN OUTCOME MEASURES: Mean preoperative and postoperative air-bone gaps
      and the changes in mean hearing loss were analyzed using a four-frequency (500,
      1,000, 2,000, and 3,000 Hz) pure tone average. Success rate was defined as
      postoperative air-bone gap within 20 dB. A one-way analysis of variance was used
      to analyze group differences. A multivariate statistical analysis was then
      undertaken to define the significant factors. RESULTS: There were no statistical
      difference between the Spiggle and Theis and the Kurz prostheses. Multivariate
      statistical analysis has identified the predictive value of the presence or
      absence of the malleus handle and the mucosal status of the middle ear in the
      prognosis of ossiculoplasties. CONCLUSION: Anatomical and technical factors
      diversely affect the functional outcome of tympano-ossiculoplasties. A better
      knowledge of their predictive value will enable accurate, preoperative,
      individual assessment when counseling patients with regard to the success of any
      proposed intervention. The use of these factors will also permit precise matching
      of future series to allow accurate comparisons.

PMID- 17195749
TI  - The dizziness handicap inventory and its relationship with functional balance
      performance.
AB  - OBJECTIVE: The purpose of this study was to describe the relation between the
      Dizziness Handicap Inventory (DHI) and balance performance measures. STUDY
      DESIGN: Retrospective case series. SETTING: Outpatient balance clinic in a
      tertiary referral center. PATIENTS: Patients referred with dizziness or imbalance
      of vestibular and nonvestibular origin. OUTCOME MEASURES: DHI, Romberg with
      Jendrassik maneuver, standing on foam, tandem Romberg, single-leg stance, the
      timed up and go test, the Dynamic Gait Index (DGI), tandem gait, and the 10-m
      walking test. RESULTS: The mean age of participants (n = 214) was 53.9 years. The
      mean DHI total score was 35.1, ranging from 0 to 96. Spearman rank correlation
      coefficients (rS) between DHI and the static balance tests were fair and ranged
      between -0.42 (p < 0.01) for single-leg stance with eyes closed and -0.51 (p <
      0.01) for single-leg stance with eyes open. Only the Romberg test with Jendrassik
      maneuver correlated weakly (rS = -0.25; p < 0.01) with the DHI. Correlations with
      the walking tests were moderate, the connection with the DGI being the strongest
      one (rS = -0.69; p < 0.01). Forty-two percent of the variance in DHI scores in
      our patients was accounted for by the DGI score (r = 0.417). CONCLUSION:
      Functional balance tests involving locomotion correlate better with DHI scores
      when compared with static balance measures. The DGI explains a large component of
      handicap in dizzy and unsteady patients, which advocates its use in these
      patients.

PMID- 17195750
TI  - Surgical management of lesions of the internal carotid artery using a modified
      Fisch type A infratemporal approach.
AB  - OBJECTIVE: To report seven cases of vascular repair of the internal carotid
      artery (ICA) using a modified Fisch type A infratemporal approach and a venous
      grafting. STUDY DESIGN: Retrospective case review. SETTING: Tertiary care center.
      PATIENTS: We have analyzed the clinical presentation, paraclinical assessment,
      and postoperative results regarding the vascular repair and the facial and
      auditory function from seven consecutive patients. All patients have been
      operated on by a multidisciplinary team of ENT and vascular surgeons. RESULTS:
      The study includes four men and three women, aged from 21 to 62 years old. Six
      patients suffered from vascular traumatic injury after motor vehicle accident (n
      = 5) or cervical manipulation (n = 1) and one patient presented an atheromatous
      stenosis. All benefited from a vascular repair with a venous grafting through a
      modified Fisch Type A infratemporal approach. No death and no new stroke were
      noted (mean follow-up, 34 mo). The postoperative angiographies showed six
      functional grafts and one asymptomatic thrombosis. Six immediate postoperative
      facial palsy occurred but recovered to Grade I or II within 6 months. There was
      one traumatic injury of the facial nerve and one postoperative anacusis. For the
      six other patients, the reconstitution of the external auditory canal and
      ossicular chain allowed to limit the hearing loss to a mean air-bone gap of 22.5
      dB (range, 15-35 dB). CONCLUSION: The lesions of the intrapetrous aspects of the
      ICA remain the subject of debates regarding the indication for a vascular repair.
      For young or in good health patients, the infratemporal approach provides a safe
      and reliable access to the horizontal segment of the ICA, offering to the
      vascular surgeons optimal conditions for the vascular repair.

PMID- 17195751
TI  - Facial paralysis associated with glomus jugulare tumors.
AB  - OBJECTIVE: To review the intraoperative findings and facial nerve management in
      nine patients who presented with facial paralysis associated with glomus jugulare
      tumors. STUDY DESIGN: A retrospective analysis of patient medical records.
      SETTING: Tertiary care academic medical center. PATIENTS: All patients who
      presented with facial paralysis and a glomus jugulare tumor who underwent
      surgical resection of their tumors at our institution. INTERVENTION: A
      postauricular infratemporal fossa approach for tumor removal and greater
      auricular interposition neural repair. MAIN OUTCOME MEASURE: Intraoperative
      facial nerve findings and long-term facial recovery. RESULTS: One hundred two
      patients underwent a postauricular infratemporal approach for resection of glomus
      jugulare tumor from July 1988 through July 2005. Nine of these patients presented
      with ipsilateral facial paralysis. The medial surface of the vertical segment was
      invaded by tumor in all nine cases. Facial recovery at 2 years was House
      Brackmann Grade III in eight patients and Grade IV in one individual. Facial
      recovery did not significantly change after 2 years (mean follow-up of 7.4
      years). DISCUSSION: Facial nerve invasion of the vertical segment occurred in 9
      (9%) of 101 patients in our series. Facial nerve resection with interposition
      grafting resulted in House-Brackmann Grade III in eight (89%) of nine patients.
      Facial nerve dissection and preservation was not possible when preoperative
      facial paralysis was evident.

PMID- 17195752
TI  - Increase of accuracy in intraoperative navigation through high-resolution flat
      panel volume computed tomography: experimental comparison with multislice
      computed tomography-based navigation.
AB  - HYPOTHESIS: High-resolution imaging, as provided by flat-panel-based volume
      computed tomography (fpVCT), could increase navigation accuracy and could
      therefore improve image-guided procedures or make novel navigated surgery
      concepts possible. BACKGROUND: Intraoperative navigation is an accepted tool in
      head and neck surgery. However, its use is limited in the lateral cranial base
      because of its low surgical accuracy. Surgical accuracy is substantially
      influenced by the resolution of the underlying data set. The fpVCT offers a
      resolution of nearly two times higher than multislice computed tomography (MSCT).
      Target registration error (TRE), as a measurement for surgical navigation
      accuracy, should decrease when navigation is based on fpVCT data sets. METHODS:
      An acrylic glass phantom with 37 fiducial points was scanned in a current MSCT
      and in an experimental fpVCT. Both data sets were imported in an optical
      navigation system. Five fiducial points were used for registration, and seven
      points were used for measuring TRE. The distance between the indicated pointer
      tip and the corresponding fiducial point in data set was measured as TRE.
      Registration and TRE measurement were repeated five times for each computed
      tomographic data set. Average TREs were calculated, and results were compared
      using t-test. RESULTS: The average TRE using MSCT (0.82 mm [standard deviation,
      0.35 mm]) was significantly higher than that using fpVCT (0.46 mm [standard
      deviation, 0.22 mm]) (p < 0.01). CONCLUSION: Submillimeter surgical navigation
      accuracy is possible using high-resolution fpVCT. This could be highly beneficial
      in cranial base surgery navigation.

PMID- 17195753
TI  - Intracochlear schwannomas.

PMID- 17195754
TI  - Trends in herpes simplex virus type 1 and 2 infections among patients diagnosed
      with genital herpes in a Finnish sexually transmitted disease clinic, 1994-2002.
AB  - OBJECTIVE: The objective of this study was to analyze the proportion of herpes
      simplex virus types 1 and 2 (HSV-1 and -2) in genital infections during a 9-year
      period (1994-2002) in a Finnish sexually transmitted disease (STD) clinic
      population. STUDY DESIGN: We analyzed prospectively the proportion of HSV-1- or 
      2-positive culture samples from our STD clinic patients with genital herpes
      during years 1994-2002 and compared the proportions of HSV-1 and HSV-2 findings
      with the age and gender of the patients. RESULTS: The proportion of HSV-1
      infections increased from 18.7% (39 of 209) in 1994-1996 to 25.9% (52 of 201) in
      2000-2002 (P = 0.032). Female patients with genital herpes and laboratory
      isolation of HSV-1 were 35.9% of the cohort from 1994-1996 and 67.3% of the
      cohort from 2000-2002. The mean age of male patients with HSV-1 decreased from
      29.3 years in 1994-1996 to 24.1 years in 2000-2002 (P = 0.023). CONCLUSIONS: An
      increase in the proportion of genital infections caused by HSV-1 was found. The
      increase was mainly the result of the increase in the number of female patients
      with HSV-1. Male patients acquire genital HSV-1 infection at a younger age than
      10 years ago.

PMID- 17195755
TI  - Data-free modeling of HIV transmission in Sub-Saharan Africa.

PMID- 17195757
TI  - Chlamydia trachomatis infection and risk of ectopic pregnancy.

PMID- 17195759
TI  - Empirical observations underestimate the proportion of HIV infections
      attributable to sexually transmitted diseases in Mwanza and Rakai STD treatment
      trials: simulation results.

PMID- 17195762
TI  - Race and mental health diagnosis are risk factors for highly active
      antiretroviral therapy failure in a military cohort despite equal access to care.
AB  - BACKGROUND: Data suggest that African Americans have lower rates of virologic
      suppression using highly active antiretroviral therapy (HAART), possibly because
      of socioeconomic status and access to care. In a US Military clinic, where
      beneficiaries have ready access to no-cost health care, the impact of several
      variables (including race) on HIV virologic suppression were examined. METHODS:
      Retrospective analysis of antiretroviral-naive patients who began HAART between
      1997 and 2003. Demographics, viral loads, CD4 cell counts, and mental health
      diagnoses were analyzed. RESULTS: The charts of 129 individuals who initiated
      their first antiretroviral regimen during the period of observation were
      evaluated. The overall efficacy of reaching viral suppression was 71% at 12
      months and 56% at 24 months. HIV suppression was achieved at 12 months by 63% of
      African Americans and 92% of whites (P = 0.001). Mental health diagnosis was
      associated with failure at 24 months (38 vs. 61%; P = 0.034). Being white (odds
      ratio = 3.5, 95% confidence interval [CI]: 1.2 to 10.3; P = 0.022) and lacking a
      mental health diagnosis (odds ratio = 8.7, 95% CI: 2.4 to 32.1; P = 0.001) were
      both associated with increased efficacy at 24 months by multivariate analysis.
      CONCLUSIONS: African-American race and the presence of a mental health diagnoses
      were independently associated with antiretroviral failure. Equal access to care
      yields high efficacy rates with HAART but does not fully equilibrate racial
      differences in virologic failure.

PMID- 17195761
TI  - Effects of active treatment discontinuation in patients with a CD4+ T-cell nadir
      greater than 350 cells/mm3: 48-week Treatment Interruption in Early Starters
      Netherlands Study (TRIESTAN).
AB  - OBJECTIVE: To evaluate the safety and efficacy of discontinuing highly active
      antiretroviral therapy (HAART) in HIV-1-positive patients who initiated HAART at
      a CD4+ T-cell count >350 cells/mm. METHODS: Eligible patients were identified
      from the Dutch AIDS Therapy Evaluation, The Netherlands (ATHENA) national
      observational cohort. Interruption or continuation of HAART was offered to all.
      RESULTS: Of 71 patients enrolled, 46 (64%) interrupted HAART (STOP group) and 25
      (36%) continued HAART (control group). The median CD4+ T-cell nadirs at the start
      of HAART were 469 (interquartile range [IQR]: 430-720) cells/mm3 and 510 (IQR:
      440-637) cells/mm3, respectively. At week 48, the median plasma HIV RNA level in
      the STOP group had stabilized at approximately pre-HAART values (4.55 log10, IQR:
      4.2-4.9 copies/mL), but the CD4+ T-cell count still exceeded the pre-HAART count
      (563 cells/mm3, IQR: 450-710 cells/mm3). Only 5 patients (11%) had reinitiated
      HAART after 48 weeks, all for personal reasons. No Centers for Disease Control
      and Prevention category events or death occurred after interruption. In 6 (13%)
      of 46 patients, mild symptoms of acute retroviral rebound syndrome (ARVS) were
      identified. No improvement was observed in mental or physical health scores. In
      37% of patients, nonnucleoside reverse transcriptase inhibitor drug
      concentrations were still detectable 1 week after stopping. CONCLUSIONS: Although
      HAART can safely be interrupted in patients with a high CD4 T-cell nadir, no
      improvement in quality of life was established. Patients can experience ARVS, the
      risk for development of resistance after treatment interruption is realistic, and
      there is a potential hazard of HIV transmission to sexual partners. We would not
      actively advise stopping treatment in patients who started treatment too early
      according to current guidelines.

PMID- 17195763
TI  - Transmission of Kaposi sarcoma-associated herpesvirus between mothers and
      children in a South African population.
AB  - BACKGROUND: To assess whether Kaposi sarcoma-associated herpesvirus (KSHV) with
      or without HIV coinfection in South African mothers is associated with higher
      KSHV seropositivity in their children. METHODS: We tested sera from 1287 South
      African children and 1179 mothers using assays for KSHV lytic K8.1 and latent
      ORF73 antigens. We computed odds ratios (ORs) and 95% confidence intervals (CIs)
      to assess associations between KSHV serostatus and risk factors. RESULTS: KSHV
      seroprevalence was 15.9% (204 of 1287 subjects) in children and 29.7% (350 of
      1179 subjects) in mothers. The risk of KSHV seropositivity was significantly
      higher in children of KSHV-seropositive mothers compared with those of KSHV
      seronegative mothers. The HIV status of mothers was marginally associated with an
      increased risk of KSHV seropositivity in their children (OR = 1.6, 95% CI: 1.0 to
      2.6; P = 0.07). KSHV seroprevalence was significantly higher in HIV-infected
      subjects (P = 0.0005), and HIV-infected subjects had significantly higher lytic
      and latent KSHV antibody levels than HIV-negative subjects. CONCLUSIONS: The risk
      of acquisition of KSHV was higher among children of KSHV-seropositive mothers.
      Although KSHV seroprevalence was significantly higher in children and mothers who
      were infected with HIV, the HIV status of the mother was only marginally
      associated with an increased risk of KSHV seropositivity in the child.

PMID- 17195764
TI  - Intrapartum transmission after mucosal exposure to HIV was not observed with
      single-dose nevirapine for mother and child.
AB  - BACKGROUND: Intrapartum transmission of HIV has been reported to be associated
      with HIV in oropharyngeal secretions (OPSs) of the child. In this study, we
      analyze the frequency of intrapartum transmission after mucosal exposure to HIV
      after administration of single-dose nevirapine. METHODS: Eighty mothers and their
      children participating in a prevention of mother-to-child transmission of HIV
      program in Uganda who took a single dose of nevirapine according to the HIVNET012
      protocol participated in the study. HIV-1 was quantified by polymerase chain
      reaction (PCR) in the mothers' and children's plasma, in cervicovaginal
      secretions (CVSs), and in the children's OPSs. Intrapartum transmission was
      defined as a positive HIV-1 RNA PCR result at week 1 or 2 after birth and a
      previously negative PCR result. RESULTS: Ninety-seven percent of children had
      detectable nevirapine in their OPS (median = 592 ng/mL). Fifty-seven (81%)
      children had HIV-negative OPSs, and 13 (19%) had HIV-positive OPSs. All children
      of mothers with HIV-negative CVSs had HIV-negative OPSs. HIV-1 levels of OPSs and
      CVSs correlated (r = 0.33, P = 0.027). None of the babies with detectable HIV-1
      in the OPSs became infected by means of intrapartum transmission. CONCLUSION:
      Intrapartum HIV infection was not observed after mucosal exposure to HIV-1 after
      administration of a single dose of nevirapine to the mother and child.

PMID- 17195765
TI  - Safety, acceptability, and tolerability of 3 topical microbicides among
      heterosexual Kenyan men.
AB  - OBJECTIVES: To compare the acceptability, tolerability, and safety of 3 topical
      microbicide formulations (62% ethyl alcohol in emollient gel and 0.1% and 0.4%
      benzalkonium chloride on a sanitary wipe) for use on male genitalia. DESIGN: This
      triple-randomized crossover study among men attending a sexually transmitted
      disease (STD) clinic in Nairobi, Kenya assigned individuals without clinical
      evidence of an STD to apply products to the penis in a predetermined random
      order, each for a 2-week period with a 1-week washout period between each
      product. Men recorded side effects and were examined for adverse events. RESULTS:
      Of 39 participants, 33 (84%) completed 6 clinic visits plus 3 home visits by
      community health workers. Participants reported use of 62% ethanol gel and 0.1%
      and 0.4% benzalkonium on 99%, 99%, and 96% of daily scheduled applications; 99%,
      98%, and 97% of preintercourse applications, and 99%, 94%, and 98% of
      postintercourse applications. All participants said they would recommend all 3
      products to a friend; 72% preferred the 62% ethanol gel, 17% the 0.1%
      benzalkonium, and 11% the 0.4% benzalkonium. One person developed objective signs
      of a genital ulcer after 14 days of 0.4% benzalkonium wipe use. CONCLUSIONS: Two
      of the 3 topical microbicides had minimal reported adverse effects, and no
      adverse effects were observed during use of the ethanol gel, which was preferred
      by most men.

PMID- 17195766
TI  - Brief report: effectiveness of combination antiretroviral therapy on survival and
      opportunistic infections in a developing world setting: an observational cohort
      study.
AB  - BACKGROUND: The prolonged effectiveness of antiretroviral therapy (ART) in a
      developing country is not well established. METHODS: An observational database
      was established at the HIV clinic of the Almenara Hospital in Lima, Peru in 1996.
      All 564 initially antiretroviral-naive HIV-infected persons (mean CD4 count of 91
      cells/mm3) who received combination ART were followed over time. RESULTS: The
      overall survival rate was 96% at year 2, 94% at year 4, and 91% at year 5. Among
      persons who initiated therapy with CD4 counts <100 cells/mm3, the overall
      survival rate at 3 years was 95%. Opportunistic infections while on ART occurred
      in 20% of persons. Patients who received 2 reverse transcriptase (RT) inhibitors
      plus a protease inhibitor had slightly better survival rates and less
      opportunistic disease in the first year of therapy as compared with those
      receiving 2 RT inhibitors and a nonnucleoside reverse transcriptase inhibitor or
      3 RT inhibitors. CONCLUSIONS: This study demonstrates the long-term effectiveness
      of ART in a developing country urban setting. It provides evidence of the
      importance of continuing global financing initiatives to provide widespread HIV
      therapy for countries in the developing world.

PMID- 17195768
TI  - Pregnancy outcomes in HIV-infected and uninfected women in rural and urban South
      Africa.
AB  - OBJECTIVE: To describe pregnancy outcomes among clade C HIV-infected and
      uninfected women in South Africa. DESIGN: A longitudinal cohort study. METHODS:
      Pregnant women attending 9 rural/urban antenatal clinics were prospectively
      recruited and followed up. Women were seen at the clinic or at home after
      delivery on 4 occasions after enrollment: 2 times within the first 2 weeks of the
      newborn's life at home, and every 2 weeks thereafter until their first health
      clinic visit when the infant was 6 weeks old. RESULTS: A total of 3465 women were
      enrolled; 615 withdrew after delivery, moved away, or had a missing or
      indeterminate HIV status, leaving 2850 women (1449 HIV-infected women). Six women
      died after delivery and there were 17 spontaneous abortions and 104 stillbirths.
      An adverse pregnancy outcome was independently associated with HIV infection
      (adjusted odds ratio [AOR] = 1.63; P = 0.015), urban enrollment (AOR = 0.39; P =
      0.020), and nonhospital delivery (AOR = 13.63; P < 0.001) as well as with a CD4
      count <200 cells/mL among HIV-infected women (AOR = 1.86; P = 0.127). Among 2529
      singleton liveborn babies, birth weight was inversely associated with maternal
      HIV (AOR = 1.45; P = 0.02) and maternal middle upper arm circumference (AOR =
      0.93; P < 0.001). Early infant mortality was not significantly associated with
      maternal HIV (hazard ratio [HR] = 1.18; P = 0.52) but was with urban sites (HR =
      0.34; P = 0.045). Low birth weight substantially increased mortality (AOR = 8.3;
      P < 0.001). HIV status of infants by 8 weeks of age (14.6%, 95% confidence
      interval: 12.5% to 17.0%) was inversely associated with maternal CD4 cell count
      and birth weight. CONCLUSIONS: HIV-infected women are at a significantly
      increased risk of adverse pregnancy outcomes. Low-birth-weight infants of HIV
      infected and uninfected women are at substantially increased risk of dying.

PMID- 17195767
TI  - Chemokine responses are increased in HIV-infected Malawian children with invasive
      pneumococcal disease.
AB  - BACKGROUND: Chemokines play an important role in the recruitment and regulation
      of leukocyte traffic during bacterial infection. The aims of this study were to
      investigate the chemokine response to invasive pneumococcal disease (IPD) and to
      examine the influence of HIV infection on the chemokine response, pneumococcal
      bacterial loads, and outcome. METHODS: We prospectively studied 95 children with
      IPD, and blood and cerebrospinal fluid (CSF) samples were taken at admission for
      the determination of chemokines, interferon-gamma (IFNgamma), and pneumococcal
      bacterial loads. RESULTS: Plasma CXCL8 and CCL2, CSF CXCL8 and CCL4, and IFNgamma
      were significantly higher in HIV-infected children than in HIV-uninfected
      children. Blood and CSF pneumococcal bacterial loads correlated with plasma and
      CSF chemokines, respectively, and were higher in HIV-infected children compared
      with HIV-uninfected children. Among HIV-infected children, plasma concentrations
      of CXCL8 and CCL2 were significantly higher in nonsurvivors than in survivors,
      but CCL5 was significantly lower. HIV-infected and HIV-uninfected children with
      IPD had higher concentrations of chemokines (except CCL5) than acutely ill HIV
      infected and HIV-uninfected children with no detectable bacterial infection. Male
      gender and low plasma CCL2 concentrations were shown to be independently
      associated with survival. CONCLUSIONS: Chemokines, in particular CCL2, are
      associated with survival in IPD and correlate with pneumococcal bacterial loads,
      disease presentation, and outcome.

PMID- 17195769
TI  - Paget disease of the temporal bone.

PMID- 17195771
TI  - Chorda tympani nerve function after middle ear surgery.
AB  - OBJECTIVE: To assess chorda tympani nerve function before and after different
      types of middle ear surgery. The hypothesis was that in cases with cholesteatoma,
      iatrogenic injury to the nerve results in less postoperative taste disturbance
      than those undergoing myringoplasty or stapedectomy. STUDY DESIGN: Prospective
      questionnaire study. SETTING: ENT Department of a district general hospital in
      England. PATIENTS: Adult patients undergoing middle ear surgery in which there
      would be elevation of the anulus. MAIN OUTCOME MEASURE: Patients' change in taste
      sensation after surgery with follow-up to demonstrate subsequent recovery.
      RESULTS: A significantly higher incidence of taste disturbance follows
      myringoplasty and stapedectomy than for procedures in which the initial diagnosis
      was cholesteatoma, regardless of the extent of injury sustained by the nerve. The
      most common complaint after chorda tympani nerve injury is of a metallic taste
      sensation. CONCLUSION: Despite the small patient cohort, the results support the
      hypothesis that iatrogenic chorda tympani nerve injury in surgery for
      cholesteatoma results in less postoperative taste disturbance than that for
      otosclerosis. This may be because the disease process of cholesteatoma renders
      the nerve hypofunctional. The situation after myringoplasty is less clear. A
      larger study may help validate these findings.

PMID- 17195772
TI  - Concurrent partnerships among adolescents in a Latino community: the Mission
      District of San Francisco, California.
AB  - OBJECTIVES: Latino adolescents in the United States are disproportionately
      affected by sexually transmitted infections, yet knowledge of their sexual
      networks, particularly concurrent sex partners, is limited. GOAL: The goal of
      this study was to describe the prevalence, patterns, and correlates of sexual
      concurrency among adolescents in an urban neighborhood. STUDY DESIGN: The authors
      conducted cross-sectional analyses of 368 sexually active youth recruited from
      public venues within a predominantly Latino neighborhood in San Francisco,
      California. RESULTS: During the prior 6 months, 20% of sexually experienced youth
      had concurrent partnerships, but this was more likely among males (27%) as
      females (12%) (odds ratio = 2.6; 95% confidence interval = 1.5-4.5). Sexually
      transmitted infection prevalence was too low to examine its association with
      concurrency. Factors that increased the likelihood of concurrency among males
      included: immigrant generation and being below grade level; and among females:
      older age and use of illegal substances. CONCLUSIONS: Ample opportunities to
      transmit sexually transmitted infections through concurrency were present, yet
      very few adolescents were infected, perhaps owing to adequate condom use within a
      neighborhood with low sexually transmitted infection prevalence.

PMID- 17195773
TI  - No evidence for a sustained increase in sexually transmitted diseases among
      heterosexuals in Amsterdam, the Netherlands: a 12-year trend analysis at the
      sexually transmitted disease outpatient clinic, Amsterdam.
AB  - OBJECTIVES: Sexually transmitted diseases (STDs) are on the rise, mainly among
      men having sex with men (MSM). GOAL: The goal of this study was to evaluate
      whether STD increases as seen in MSM are also visible among heterosexuals. STUDY
      DESIGN: Attendees of the STD clinic in Amsterdam, The Netherlands, are routinely
      tested for chlamydia, gonorrhea, and syphilis. Additionally, all women are tested
      for trichomoniasis. STD time trends of heterosexual attendees between 1994 and
      2005 were analyzed by logistic regression and generalized linear models with a
      negative binomial distribution. RESULTS: The number of consultations doubled
      since 1994. However, no long-term increase was seen in the number of syphilis and
      gonorrhea infections. Additionally, the trichomonas prevalence declined. However,
      the number of chlamydia infections increased over time. CONCLUSIONS: Although the
      number of attendees increased, no evidence for increasing STD incidence was found
      among heterosexuals. The increase in chlamydia infections can probably be
      explained by increased screening resulting from increased numbers of attendees.

PMID- 17195781
TI  - Determining differential diagnosis by practical observation.

PMID- 17195782
TI  - Wound care challenges faced in iran.

PMID- 17195783
TI  - Update charge encounter sheets and charge description masters.

PMID- 17195784
TI  - The role of nutritional therapy in palliative care.

PMID- 17195785
TI  - Certification and education: do they affect pressure ulcer knowledge in nursing?
AB  - OBJECTIVE: To determine whether wound care certification and education affect
      nursing knowledge. This study examined pressure ulcer knowledge among registered
      nurses who were (1) certified in wound care, (2) certified in specialty areas
      other than wound care, or (3) not certified in any specialty area. DESIGN: A
      convenience sample of 460 nurses, located in both urban and rural areas, provided
      demographic information and completed a standardized pressure ulcer knowledge
      test using (Pieper Pressure Ulcer Knowledge Tool). RESULTS: The mean standardized
      test score for the total sample was 78%, with nurses certified in wound care
      scoring 89%, nurses certified in specialties other than wound care scoring 78%,
      and nurses receiving no certification scoring 76.5%. CONCLUSION: Wound care
      certification and education significantly affect nursing knowledge.

PMID- 17195786
TI  - The role of moisture balance in wound healing.
AB  - PURPOSE: To provide an overview of moisture balance and its importance in wound
      healing. TARGET AUDIENCE: This continuing education activity is intended for
      physicians and nurses with an interest in wound care. OBJECTIVES: After reading
      this article and taking the test, the reader should be able to: 1. Discuss the
      wound healing process and wound assessment. 2. Describe the types of dressings
      available and how they meet the needs of the individual patient.

PMID- 17195788
TI  - The pediatric outcomes data collection instrument detects improvements for
      children with ambulatory cerebral palsy after orthopaedic intervention.
AB  - The purpose of this study was to assess whether the Pediatric Outcomes Data
      Collection Instrument (PODCI) was able to detect changes in function, as
      perceived by the parents of children and adolescents with cerebral palsy who had
      undergone lower limb soft tissue and/or bony surgeries. This was a retrospective
      study of 80 ambulatory patients who were seen in the motion laboratory and
      classified with the Gross Motor Functional Classification System (GMFCS).
      Significant changes (P < 0.05) were detected in the PODCI scores for upper
      extremity function, transfers and mobility, physical function and sports, and
      global function after surgery, by approximately 4% to 5%, whereas comfort (pain
      free) did not significantly change. There was a significant difference in the
      PODCI scores preoperatively between GMFCS levels I, II, and III for upper
      extremity function, transfers and mobility, physical function and sports, and
      global function. Postoperative improvements were of equal magnitude for each
      GMFCS level. This suggests that the PODCI did not have a ceiling effect for high
      functioning children. Age (+/-10 years) and surgery (soft tissue/soft tissue plus
      bony) were not significant factors for any of the subcategories preoperative to
      postoperative. In conclusion, the PODCI detected improvement as perceived by the
      parents in ambulatory children with cerebral palsy after lower-limb soft tissue
      and/or bony surgeries in 4 areas by a magnitude of approximately 4% to 5%.

PMID- 17195789
TI  - Correlation of the Edinburgh Gait Score with the Gillette Gait Index, the
      Gillette Functional Assessment Questionnaire, and dimensionless speed.
AB  - This study examines the correlation of the Edinburgh Gait Score (EGS) with the
      Gillette Gait Index (GGI; formerly the Normalcy Index), the Gillette Functional
      Assessment Questionnaire, and speed, all of which are used as measures of gait
      quality or function. Scores were computed for 58 subjects, all with a diagnosis
      of cerebral palsy. The correlation of the EGS with all of the other scores was
      found to be significant, with r2 ranging from 0.26 to 0.79. The strongest
      correlation was found with the GGI, which may reflect common features in the
      derivation of both of these scores, although the EGS was derived from
      observational gait analysis and the GGI from principal component analysis of
      variables from computerized 3-dimensional gait data. We conclude that the EGS
      shows good concurrent validity with alternative gait assessment scores.

PMID- 17195790
TI  - Anterior knee pain in children with cerebral palsy.
AB  - Anterior knee pain arising from the patellofemoral joint may be a significant
      problem in the cerebral palsy (CP) population. The aim of this study was to
      classify patients with anterior knee pain based on etiology and organize
      orthopaedic management based on this classification. This study was a
      retrospective chart review of patients with CP and anterior knee pain admitted to
      the orthopaedic outpatient clinic between 1991 and 2003. Children with CP who had
      intractable anterior knee pain despite 6 months of conservative treatment with at
      least 2 years' follow-up were identified and included. The medical records,
      radiographs, and treatment protocols were screened. Patients were classified into
      3 groups according to pathology. Group I consisted of 7 children with patella
      alta only. Group II consisted of 7 children with patellar inferior pole
      fractures. Group III consisted of 13 children with subluxated or dislocated
      patellas. Conservative treatment methods such as anti-inflammatory drugs, local
      ice packs, stretching exercises, and braces should be the first step in
      treatment. For those patients in whom conservative treatment was not effective,
      surgical treatment alternatives were discussed. Knee pain resolved in all
      patients after surgical treatment of the underlying pathology. Gait analysis can
      be performed for patients with patellofemoral subluxations to evaluate the
      rotational malalignment of the tibia and femur. In conclusion, anterior knee pain
      arising from the patellofemoral joint in patients with CP should be evaluated and
      treated to prevent future functional deterioration.

PMID- 17195791
TI  - Percutaneous pinning of pediatric supracondylar humerus fractures with the
      semisterile technique: the Miami experience.
AB  - Pediatric supracondylar humerus fractures are common injuries. The standard of
      care for management of displaced supracondylar fractures has become closed
      reduction and percutaneous pinning of the fracture in the operating room. We have
      been using a "semisterile" surgical technique, similar to what is used when
      placing a traction pin at the bedside. The purpose of this study was to evaluate
      our cases from 2000-2004 requiring closed reduction and percutaneous pinning to
      determine if this method had an infection rate comparable to what is reported in
      the literature. A total of 304 cases were identified. There were no superficial
      pin track infections or deep infections requiring treatment in any patient. A
      review of the literature regarding percutaneous pinning of supracondylar humerus
      fractures reveals an overall infection rate of 2.34% (45/1922) with a deep
      infection rate of 0.47% (9/1922). Consequently, the use of the semisterile
      technique is safe and an efficient way to handle these cases in saving time,
      cost, and materials. We also found that the administration of perioperative
      antibiotics may not be necessary as 68% of our patients did not receive any
      antibiotics during the perioperative or postoperative period. Finally, we found
      that 37% of our patients were discharged home the same day the surgery was
      performed, and there were no cases of compartment syndrome or Volkmann ischemic
      contracture. This indicates that observation overnight in the hospital may not be
      necessary for every patient.

PMID- 17195792
TI  - Digital radiographic measurement of the atlantodental interval in children.
AB  - The atlantodental interval (ADI) is assessed after trauma to the head and neck
      region to determine whether the transverse ligament of the atlas is intact.
      Atlantodental interval measurement from conventional screen-film radiographs is
      characterized by the need for magnification correction and by low reliability.
      Assessment of normal ADI values using digital radiography with computer-assisted
      measurement has not been reported. We compared with published values the digital
      radiographic measurements of ADI in children, examined the reliability of
      measurements, and examined the interaction between age, sex and ADI. Computer
      assisted digital measurements of ADI in 101 children, aged 1 to 12 years, were
      obtained from lateral supine head-neutral radiographs. We found intraobserver
      reliability of 0.72 and 0.85, interobserver reliability of 0.50, a maximum ADI
      value of 3.5 mm, no effect of sex and age, and weak evidence for an interaction
      between sex and age. Computer-assisted digital ADI measurement provides higher
      intraobserver reliability than what has previously been reported, and
      interobserver reliability and a maximum ADI value similar to that found in the
      literature.

PMID- 17195793
TI  - A reappraisal of the Ortolani examination in children with developmental
      dysplasia of the hip.
AB  - The Ortolani maneuver is currently accepted as an accurate test to detect
      developmental dislocation of the hip. However, the clinical sign does not always
      correlate with the findings seen on ultrasound. The ultrasound-documented
      position of the femoral head was correlated with the result of the clinical
      Ortolani examination to better understand the value and validity of the Ortolani
      test. Two populations were compared: hips with a positive Ortolani sign and hips
      with a negative Ortolani sign but with an ultrasound-documented dislocated hip.
      In the Ortolani-positive group, there were 45 patients (53 affected hips), and in
      the Ortolani-negative group, there were 24 patients (25 dislocated hips).
      Position of the femoral head at rest, side of involvement, and sex showed no
      significant difference between the Ortolani-positive and -negative groups. Mean
      age of patients in the Ortolani-positive group was less (mean, 28 days) and was
      statistically different (P < 0.05) from those in the Ortolani-negative group
      (mean, 91 days). In conclusion, dislocated hips that show similar femoral head
      movement can produce an Ortolani-positive examination in a younger patient and an
      Ortolani-negative examination in an older patient. The classic clinical method
      described by Ortolani for detecting hip dislocation in which the thigh of the
      affected hip is abducted and the femoral head was thought to be reducing into the
      acetabulum can be erroneous. All Ortolani-positive hips were abnormal, as the
      sensation characteristic of a positive Ortolani examination may be felt without
      full reduction and, in some cases, with no reduction, as documented by
      ultrasound.

PMID- 17195794
TI  - Late developmental dislocation of the hip after initial normal evaluation: a
      report of five cases.
AB  - Developmental dysplasia of the hip (DDH) denotes a wide spectrum of pathologies
      ranging from hip instability to frank dislocation. The current understanding is
      that cases of late diagnosis were missed during the newborn period. However,
      there is some evidence that a number of hip subluxations or dislocations may have
      been clinically stable in the neonatal period, but dislocate late. We present 5
      cases of otherwise healthy children with normal physical examinations and hip
      radiographs in the first 3 months of life who later developed hip dislocations.
      Four of the 5 cases required surgical open reduction. In light of these cases and
      others in the literature, normal neonatal screening for DDH does not assure that
      continued normal development of the hip joint will happen. Our study confirms the
      existence of another entity in the wide spectrum of DDH: the late hip
      dislocation. Therefore, hip evaluations should be continued beyond the neonatal
      period until the child begins to walk. Parents should be informed that hip
      dislocation can occur in a late form, and they should be encouraged to take their
      children for repeated evaluations even if the neonatal screening is normal.

PMID- 17195795
TI  - Treatment of hip dislocation in Kabuki syndrome: a report of three hips in two
      patients.
AB  - The incidence of hip dislocation in Kabuki syndrome (KS) is thought to be between
      18% and 40%. Although hip dislocation is apparently well recognized in KS, to our
      knowledge, its management and outcome have not previously been addressed in the
      literature. We report 2 children (3 hips) with KS and hip dislocation who
      underwent surgical treatment with a minimum of 24-month follow-up. In addition,
      we review the current literature on the treatment of orthopaedic problems in KS.

PMID- 17195796
TI  - The deep fascia in response to leg lengthening with particular reference to the
      tension-stress principle.
AB  - OBJECTIVE: To investigate the morphological changes of deep fascia subjected to
      distraction in a rabbit model of leg lengthening. METHODS: The animal model of
      leg lengthening was established in 20 New Zealand white rabbits using a
      unilateral external fixator with 4 half pins medially fixed to the tibia, and
      osteotomy was performed between the second and the third pins. The distraction
      was initiated 7 days after the osteotomy procedure, with the rate of 1 and 2 mm/d
      in 2 steps, and proceeded until 10% and 20% increases in the initial length of
      the tibia had been achieved. The deep fascia samples were studied by the
      hematoxylin-eosin stain, the Masson-trichome staining, and the JEM2000EX electron
      microscopy. RESULTS: Under light, the cross section of normal deep fascia without
      distraction consisted of 3 layers. Whereas in the longitudinal sections, the deep
      fascia consisted of wavy collagen fibers. The normal deep fascia consisted of
      fibrocyte and collagenous fibrils under electron microscopy. After leg
      lengthening, the morphology of the fascia distracted at each rate changed. Under
      light, the fascia distracted at each rate kept the normal 3 layers in the cross
      sections. The fascia subjected to distraction at a rate of 2 mm/d showed injuries
      of collagen fibers. Under electron microscopy, the fascia distracted at a rate of
      2 mm/d showed active metabolism to repair the necrotic collagenous fibrils.
      Whereas the fascia subjected to distraction at a rate of 1 mm/d showed
      regenerative changes. The endotheliocyte of capillaries within the deep fascia
      subjected to distraction at a rate of 1mm/d with 20% lengthening of tibia was
      metabolically active. CONCLUSIONS: The tension stress, which is applied in leg
      lengthening and deformity correction as described by Ilizarov, has a great effect
      upon the fascia, which is always related to the function of the involved limb.
      The appropriate regimen of distraction at the rate of 1 mm/d with 20% lengthening
      of tibia leads to the regenerative changes in deep fascia, ultimately close to
      the morphological structure of normal under the condition of this investigation.

PMID- 17195797
TI  - Reliability analysis for radiographic measurement of limb length discrepancy:
      full-length standing anteroposterior radiograph versus scanogram.
AB  - Patients with limb length discrepancy (LLD) often have associated angular
      deformities requiring a standing full-length radiograph of the lower limb in
      addition to a scanogram. The purpose of our study was to determine the
      intraobserver and interobserver reliability of measuring LLD with both
      techniques, using computed radiography. The LLD was measured on 70 supine
      scanograms and standing anteroposterior radiographs of the lower extremity by 5
      blinded observers on 2 separate occasions. Intraclass correlation coefficient
      (ICC) and mean absolute difference (in millimeters) was calculated to assess
      intraobserver and interobserver reliability and found to be excellent for both
      radiographic techniques. Intraobserver ICC and mean absolute difference was 0.975
      to 0.995 and 1.5 to 2.6 mm for scanogram and 0.939 to 0.996 and 1.5 to 4.6 mm for
      the standing radiograph, respectively. Repeated measurements for both
      radiographic studies were within 5 mm of the first measurement greater than 90%
      and within 10 mm greater than 95% of times. Interobserver ICC and mean absolute
      difference was 0.979 and 2.6 mm for scanogram and 0.968 and 3.0 mm for the
      standing radiograph. The reliability was excellent irrespective of age, sex, and
      underlying diagnosis other than Blount disease, which had good reliability. A
      standing anteroposterior radiograph of the lower extremity should be the imaging
      modality of choice when evaluating patients with limb length inequality who may
      have angular deformities because it allows a comprehensive evaluation of the
      extremity and is as reliable as a scanogram for measuring LLD. This approach may
      decrease the radiation exposure and financial burden involved in assessing
      patients with unequal limb lengths.

PMID- 17195798
TI  - Function of children with myelodysplasia and lower extremity amputations.
AB  - This is a retrospective study of the functional status of children who underwent
      a lower extremity amputation for complications of myelodysplasia. With a
      computerized surgical database, 12 children with myelodysplasia who underwent an
      amputation at the Boyd level or above at a single children's referral hospital
      between 1983 and 2001 were identified. Four patients could not be contacted, but
      the remaining 8 patients were evaluated through chart review and interview to
      assess the impact of the amputation on their function. With a mean follow-up time
      of 9 years (range, 5-15 years), all 6 of the patients with a below-knee or Boyd
      amputation continued to ambulate using a prosthesis. Most patients occasionally
      reported having ulcers on their residual limb, but these cases were easily
      managed and did not result in amputation revisions.The only patient in this
      series with an above-knee amputation and the only patient with a knee
      disarticulation were exclusively wheelchair ambulators and no longer owned a
      prosthesis. This study supports the notion that children with myelodysplasia can
      have amputations and successfully wear a prosthesis to maintain their ambulation.

PMID- 17195799
TI  - The contralateral foot in children with unilateral clubfoot: a study of pressures
      and forces involved in gait.
AB  - The unaffected contralateral side of patients with unilateral clubfeet has
      sometimes been taken as control in foot pressure measurement studies. However, it
      has never been shown that the pressure pattern under the contralateral foot is
      similar to a normal foot. Sixteen patients with unilateral clubfoot and 110
      normal subjects took part in this study. All participants were aged from 4 to 8
      years. Studies comprised clinical examination and foot pressure measurements in
      barefoot walking. Evaluations of the measurements were completed by the
      calculation of forces acting under 10 anatomical foot areas normalized to ground
      reaction force at foot-flat and push-off. Significant differences in peak
      pressure were observed between the control group and the contralateral foot of
      patients under the heel and the metatarsals 1 to 4. Significant differences in
      the forces at foot-flat and push-off are seen especially in the midfoot. Both
      sides of the patients with unilateral clubfeet exert significantly less ground
      reaction force than normal subjects. Different pressure and force distributions
      of clubfoot children on their contralateral side compared with the normal feet of
      the control group may indicate differences in the general control pattern
      generated by the central nervous system. Differences can still be observed after
      normalization of the forces. We therefore conclude that when foot pressure
      measurements are made with clubfeet, it might be advisable to use a collective of
      normal feet, instead of the contralateral foot, for comparison.

PMID- 17195800
TI  - No association between residual forefoot adduction and the position of the
      navicular in clubfeet treated by posterior release.
AB  - Medial displacement of the navicular has been considered a major explanation for
      residual forefoot adduction (FFA) in congenital clubfoot and also a frequent
      reason for dissatisfaction after limited surgery. In this study, it was
      hypothesized that there would be an association between the degree of medial
      displacement of the navicular and residual FFA in clubfeet. The position of the
      navicular was retrospectively measured by ultrasonography in 49 clubfeet in 35
      children at ages 3 to 6 years and correlated to residual FFA measured on
      footprints and radiographs (talo-first metatarsal angle). In the 49 clubfeet, the
      navicular was significantly more medially displaced toward the medial malleolus
      than in the 21 contralateral normal feet (P < 0.001). However, there was no
      correlation between the degree of medial displacement of the navicular and the
      degree of FFA measured on footprints (P = 0.690) or on radiographs (P = 0.390).
      Thus, there were clubfeet with straight forefoot and a medially displaced
      navicular, that is, "spurious correction," and clubfeet with FFA and the
      navicular in correct position in relation to the head of the talus. Both patient
      satisfaction and foot score declined with larger FFA. The results support the
      view that ultrasonography is a helpful tool for assessing the position of the
      navicular. The critical issue for analysis is whether the FFA is due to
      malalignment in the talonavicular joint or more distally.

PMID- 17195801
TI  - Giant cell tumor of tendon sheath: largest single series in children.
AB  - Giant cell tumors of tendon sheath (GCTTS) are rare in children. We hypothesized
      that GCTTS in children probably behave in a similar manner to the adult lesions,
      with regard to clinical features, imaging characteristics, histology, and
      recurrence rates after surgical excision. We retrospectively reviewed 29 children
      diagnosed and treated for GCTTS during a 16-year period and evaluated the above
      characteristics to compare these results with published data for adult patients.
      A telephone questionnaire survey was also conducted to assess the current
      symptoms and function, satisfaction with procedure, and incidence of recurrence.
      In children, we noted similar predilection for lesions in both upper and lower
      extremities. Most cases, 28 (96%) of 29, presented with a gradual enlarging soft
      tissue mass. Plain radiography demonstrated soft tissue swelling in 50% of cases.
      Magnetic resonance imaging features were noted to be variable, although low
      signal intensity on T1- and T2-weighted images was noted in most lesions.
      Incisional biopsy with intraoperative frozen section and histological evaluation
      was the gold standard for accurate diagnosis. We noted no recurrence at final
      follow-up in any of our cases. Twenty-two (75%) of these 29 patients had follow
      up of more than 2 years, with no recurrence, and the remaining 7 had follow-up
      between 1 to 2 years, which may seemingly be adequate from perspective of
      expected time interval for early recurrences. Meticulous dissection and excision
      with appropriate use of magnifying surgical loupes are likely factors that may
      help to minimize the recurrence rate.

PMID- 17195802
TI  - Focal fibrocartilaginous dysplasia ("fibrous periosteal inclusion"): an
      additional series of eleven cases and literature review.
AB  - Focal fibrocartilaginous dysplasia (FFCD) is a benign condition first described
      in 1985 as a cause of tibia vara. We are reporting on 11 cases. The lesions
      involved proximal tibia (9 cases), distal femur (1 case), and distal ulna (1
      case). We believe that this entity represents a bony anchor preventing natural
      sliding of the periosteum during growth (an "epiphysiodesis-like" effect). For
      the tibia, we believe this is the pes anserinus. We are suggesting that this
      entity be called a "fibrous periostal inclusion." Treatment indications result
      from this concept: (1) for tibial lesions with a metaphyseal-diaphyseal angle
      less than 20 degrees observation for 6 to 12 months; (2) if the deformity
      improves, the tether likely broke spontaneously, and no treatment is required;
      and (3) curettage early if the deformity worsens. This will be followed by rapid
      correction into physiological valgus (tibia) and prevent the need for osteotomy.
      Early curettage for other less common locations is recommended.

PMID- 17195803
TI  - The musculoskeletal manifestations of the Coffin-Lowry syndrome.
AB  - Coffin-Lowry syndrome (CLS) is a rare genetic disorder characterized by
      craniofacial abnormalities, mental retardation, short stature, and hypotonia.
      Patients with CLS may present with multiple musculoskeletal abnormalities. The
      purpose of this study was to identify and characterize the musculoskeletal
      findings in 10 patients with CLS. Eight patients presented with thoracolumbar
      kyphosis or kyphoscoliosis, with a mean Cobb angle of 45 degrees in the coronal
      plane and 31 degrees of thoracolumbar kyphosis. These may be progressive and
      difficult to treat, needing early surgical treatment. Close follow-up of the
      spinal deformities is strongly recommended to document progression. Sixty percent
      of the patients presented with bilateral flexible and painless planovalgus
      deformities. Hypoplasia of the ilium and hand deformities are common but do not
      seem to cause any functional problems. Observation is recommended for these
      asymptomatic hand, foot, and pelvic findings.

PMID- 17195804
TI  - Back pain in adolescents: assessment with integrated 18F-fluoride positron
      emission tomography-computed tomography.
AB  - The aim of the present study was to assess the ability of a novel bone imaging
      technique to diagnose accurately the cause for back pain as an isolated and
      presenting complaint in adolescents. An integrated 18F-fluoride positron-emission
      tomography-computed tomography (PET-CT) study was performed at the same setting
      without changing the patients' position, followed by generation of fused images
      of functional and anatomical data. Fifteen subjects were included in the study.
      The interpretation of PET-CT fused images was based on increased 18F-fluoride
      uptake and the corresponding CT-located abnormality. Ten patients had positive
      findings that included 4 cases of spondylolysis (3 of them active), 3 frank
      fractures (2 of the transverse process and 1 of the facet), 2 osteoid osteomas, 1
      osteitis pubis, 1 sacroiliitis, and 2 herniated disks. Three patients presented 2
      coexisting pathologies. Treatment was tailored based on final diagnosis. In 5
      patients, in whom no abnormality was identified, the back pain resolved
      spontaneously. The 18F-fluoride PET-CT can detect spinal lesions with high
      diagnostic accuracy in adolescents with back pain. Considering the associated
      costs and radiation exposure, it should be used at present only in cases of long
      standing and disabling back pain in which other imaging modalities were
      inconclusive.

PMID- 17195805
TI  - Insurance status and delay in orthotic treatment in children.
AB  - OBJECTIVE: To determine if the type of health insurance is associated with a
      delay in children obtaining orthoses. METHODS: The medical records of 60 children
      who were prescribed an ankle-foot orthosis (AFO) or thoracolumbosacral orthosis
      (TLSO) were retrospectively reviewed. Ten children were randomly chosen with
      either of 3 types of insurance (government, health maintenance organizations
      [HMOs], and preferred provider organizations [PPOs]) with an orthosis provided by
      a single supplier. The time interval between prescription and insurance company
      authorization was recorded, as well as the interval between prescription and
      procurement of the orthosis. RESULTS: There were significant differences in the
      time from prescription to authorization of orthoses between insurance types (P =
      0.001) and time from authorization until brace procurement between insurance
      types (P = 0.01). Children with PPO insurance received authorization for an AFO
      faster than children with government insurance or an HMO (P < 0.05). Children
      with government insurance received authorization for a TLSO significantly later
      than children with PPO insurance (P = 0.004) or HMO insurance (P = 0.03). The
      difference in time between authorization and procurement of a TLSO in children
      with PPO insurance (36 days) was strikingly different from that of children with
      government insurance (123 days) (P = 0.003). DISCUSSION: This study documents
      that children with government insurance face delays in obtaining orthotic
      treatment compared with children with PPO insurance. The delay in the procurement
      of the more expensive brace (TLSO is approximately 4 times the cost of an AFO)
      correlated to more striking delays in the government-insured population.

PMID- 17195806
TI  - Orthopaedic complications of myotubular myopathy.
AB  - Myotubular myopathy is a rare genetic disease that was uniformly fatal until
      recent developments in long-term ventilation. Today, however, it is not unusual
      for a patient to live into the second decade. The orthopaedic manifestations of
      the disease have not been reported in the literature. We present our experience
      with complications related to the spine and extremities in a series of 4 patients
      with this disease who have survived beyond early childhood.

PMID- 17195808
TI  - Re: kinematic and kinetic evaluation of the ankle joint before and after tendo
      Achilles lengthening in patients with spastic diplegia -- J Pediatr Orthop
      2005;25:479-483.

PMID- 17195809
TI  - Congenital scoliosis: a review and update.
AB  - Vertebral anomalies causing congenital scoliosis are classified on the basis of
      failures of formation, segmentation, or both. The natural history depends on the
      type of anomaly and the location of anomaly. Patient evaluation focuses on the
      history and physical examination, followed by appropriate imaging modalities. The
      hallmark of surgical treatment is early intervention before the development of
      large curvatures. The surgical treatment of a congenital deformity mandates the
      use of neurological monitoring to minimize the risk of perioperative neurological
      deficit. Modern surgical techniques have evolved to include the routine use of
      spinal instrumentation. Patients with associated chest wall deformities or large
      compensatory curves may be candidates for vertical expansion prosthetic titanium
      rib placement or growing rods insertion to maximize growth.

PMID- 17195810
TI  - Alignments and clinical results in conventional and navigated total knee
      arthroplasty.
AB  - In this prospective, randomized, controlled study, we compared the performance of
      conventional and navigated total knee arthroplasties. Component alignment was
      measured in 60 patients operated on using navigation and in 60 patients operated
      on using the conventional technique. The groups then were divided into a
      subpopulation to measure alignments of the distal femoral cuts in the three
      anatomic planes, the proximal tibial cut in the frontal and sagittal planes, and
      the resulting lower limb mechanical axis in the frontal plane. Postoperative
      weightbearing long-view radiographs were evaluated as were clinical results using
      three standard questionnaires at 28 months followup. The intraoperative
      measurements (mean +/- standard deviation) at the resection planes showed
      navigated surgeries result in more accurate alignments than conventional
      surgeries for the femur: in the frontal plane, 0.1 degrees +/- 0.9 degrees and
      0.7 degrees +/- 1.6 degrees valgus, respectively; in the sagittal plane, 1.1
      degrees +/- 1.8 degrees and 2.8 degrees +/- 2.0 degrees flexion; and in the
      transversal plane, 0.1 degrees +/- 1.2 degrees and 0.9 degrees +/- 1.7 degrees
      internal rotation. The navigated technique also reduced the number of cases with
      final mechanical axes greater than 3 degrees from 20.0% to 1.7%. Postoperative
      radiographs showed better component alignment using navigation, particularly at
      the femur. However, clinical scoring systems showed this radiographic improvement
      did not necessarily result in a better clinical outcome at short-term followup.

PMID- 17195811
TI  - Case report: vertebral compression fracture in a fused and instrumented lumbar
      segment.
AB  - Although vertebral fractures in fused spinal segments have been reported, we are
      not aware of any descriptions of vertebral body compression fractures in solidly
      fused and instrumented segments. We report a patient who sustained a vertebral
      body compression fracture of the L1 vertebra in an instrumented and fused spinal
      segment from T10 to L5. The fracture occurred during self-insertion of a rectal
      suppository. No intervention was required to treat the fracture, and there was no
      long-term clinical effect.

PMID- 17195812
TI  - Persistence of the mini pivot shift after anatomically placed anterior cruciate
      ligament reconstruction.
AB  - We hypothesized that traces of pivot-shift instability (a minipivot) would
      persist after anterior cruciate ligament reconstruction in some knees despite
      objective restoration of anteroposterior laxity to normal. We tested intact
      cadaver knees after anterior cruciate ligament transection and then after
      anatomically placed single-bundle anterior cruciate ligament reconstructions. We
      measured the rotational laxities and pivot-shift kinematics over a range of graft
      tensions. Increasing graft tension decreased anteroposterior laxity;
      anteroposterior laxity was greater than normal at 0 and 10 N tensions but not
      different than normal at 20 to 60 N tensions. Anterior cruciate ligament
      deficiency had little effect on rotation laxity, and reconstruction had little
      effect on rotational laxity, which was not reduced by increasing graft tension.
      During the pivot-shift test, increasing graft tension reduced the anteroposterior
      subluxation-reduction events, but tibial rotational was not restored to normal.
      More sophisticated reconstruction methods may be required to control rotation.
      Objective restoration of anteroposterior laxity to normal does not necessarily
      return knee kinematics, especially rotational behavior, to normal.

PMID- 17195813
TI  - Clinical epidemiology of long-bone fractures in patients receiving hemodialysis.
AB  - Although prevention of metabolic bone disease is a principal component of
      management of end-stage renal disease, the clinical epidemiology of long-bone
      fractures is not completely understood. Hospital discharge claims from 1994
      through 1999 for 7159 subjects in the Dialysis Morbidity and Mortality Study were
      used to quantify incidence and risk factors of long-bone fractures and to test
      the hypothesis that long-bone fractures are associated with cardiovascular and
      infectious events and death in patients receiving hemodialysis. The incidence of
      long-bone fractures was 16.93 per 1000 patient-years, with the femoral neck being
      the most common site (59.8%); multivariate analysis revealed greater risk with
      older age, female gender, diabetes, more years receiving dialysis, and
      cardiovascular disease, and lower risk with African American race, increasing
      body mass index, parathyroid hormone values in the fourth quintile (227.1-538.0
      pg/mL), and renal transplantation during followup. Postfracture mortality rates
      were 522.57 per 1000 patient years (versus 215.35 in the overall population).
      Time-dependent analysis suggested the adverse prognosis of long-bone fractures
      was related to subsequent congestive heart failure, stroke, pulmonary embolism,
      pneumonia, and septicemia. Long-bone fractures are common in patients receiving
      dialysis; their adverse prognostic implications may be linked to major
      cardiovascular and infectious events.

PMID- 17195815
TI  - Genetics of arthrogryposis: linkage analysis approach.
AB  - Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of congenital
      contracture syndromes, some of which are hereditary. To date, four genetic loci
      associated with autosomal recessive arthrogryposis syndromes have been identified
      using the powerful tools of genome-wide linkage analysis and homozygosity
      mapping. In the consanguineous inbred Bedouin population in southern Israel there
      is an unusually high incidence of hereditary arthrogryposis. We hypothesized the
      high incidence of this phenotype in this specific cohort might be due to a
      founder effect: a mutation that occurred several generations ago, spread
      throughout various tribes in that population in recent generations and causes the
      phenotype in its homozygous form. Using linkage analysis studies, we showed the
      hereditary arthrogryposis in those tribes does not stem from a single genetic
      defect. Thus, there is genetic heterogeneity of congenital arthrogryposis in this
      population: the same phenotype is caused by mutations in different genes, yet to
      be unraveled.

PMID- 17195816
TI  - A method to evaluate contractures effects during the gait of children with
      Duchenne dystrophy.
AB  - Joint contractures are the second major impairment affecting the locomotor system
      of children with Duchenne muscular dystrophy (DMD). While the negative influence
      of joint contractures has been documented, the passive moments produced by joint
      contractures could benefit the gait of patients with muscle weakness. We describe
      a biomechanical model that quantifies the mechanical contribution of ankle and
      hip flexion contractures to the gait of DMD children. Kinematic and kinetic
      parameters were measured under the same experimental conditions during the gait
      and passive resistance assessment of two subjects: one healthy child as a
      control, and one child with DMD. The child with DMD had a plantar flexion
      contracture and a greater ankle stiffness coefficient than the control child.
      During gait, the contribution of the ankle passive moment to the net moment was
      more important for the child with DMD than for the control child. At the hip,
      passive joint moments and passive moment contribution were more important for the
      control child but this was not related to the presence of hip flexion
      contracture. These preliminary results suggest the model might be used to
      evaluate contractures effect on a larger cohort of subjects.

PMID- 17195814
TI  - Myofibroblast upregulators are elevated in joint capsules in posttraumatic
      contractures.
AB  - We hypothesized specific growth factors are increased in the elbow capsules of
      patients with post traumatic elbow contractures. A model of surgically induced
      joint contracture in rabbit knees was developed to study the growth factor
      expression in joint contractures. This study demonstrates this model mimics the
      human condition and analyzes how the growth factor levels decrease with time in
      rabbit knees with contractures. Reverse transcription polymerase chain reaction
      was used to measure mRNA levels of transforming growth factor-beta1, connective
      tissue growth factor, ED-A of fibronectin, and alpha-smooth muscle actin
      normalized to a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase. In
      the joint capsules of patients with elbow contractures, mRNA levels were
      increased for transforming growth factor- beta1, connective tissue growth factor,
      and alpha-smooth muscle actin. In the joint capsules of rabbit knees with
      contractures, mRNA levels were increased for transforming growth factor- beta1,
      connective tissue growth factor, ED-A of fibronectin, and alpha-smooth muscle
      actin. The mRNA levels for transforming growth factor-beta1, connective tissue
      growth factor, and alpha-smooth muscle actin decreased with time in rabbit knees.
      The elevated levels of these myofibroblast up-regulators and fibrogenic growth
      factors could explain the previously reported increase in myofibroblasts and
      collagen mRNA levels. The rabbit knee model correlated well with the human post
      traumatic elbow contractures.

PMID- 17195817
TI  - Genetic influences on joint contractures secondary to immobilization.
AB  - The primary research question of this study queries whether, beyond environmental
      conditions, genetic factors affect the development of joint contractures. We
      hypothesized that intrinsic genetic factors influence the severity of joint
      contractures developing secondary to joint immobilization. Forty rats from four
      inbred rat strains had one leg immobilized in knee flexion for 4 weeks. The
      contracture was measured mechanically as the lack of range of motion to a
      standardized torque. Using the contralateral leg as a control, the average
      severity of the contracture could be calculated and compared between strains. All
      immobilized legs presented knee contractures after 4 weeks of immobilization. Two
      strains (Dark Agouti and Fisher 344) showed a larger mean knee contracture than
      those of the two other rat strains (Augustus Copenhagen Irish and Brown Norway).
      Environmental factors, such as immobility, are usually identified as a cause of a
      joint contracture. These results demonstrate that, in addition to mechanical
      factors in the environment of a joint, intrinsic genetic factors participate in
      the process leading to joint contracture. This demonstration has important
      consequences for directing future research and may lead to interventions to help
      patients at risk of developing joint contractures.

PMID- 17195818
TI  - Industry-funded positive studies not associated with better design or larger
      size.
AB  - Previous studies have associated commercial funding with positive outcomes in
      orthopaedic research. Those reports, however, failed to account for potential
      confounding variables that can lead to a disproportion of positive outcomes,
      including sample size, study design, and study quality. We tested the hypothesis
      that nonscientific factors (funding source, orthopaedic subspecialty, and
      geographic region of origin) are associated with positive study outcomes, but not
      the result of differences in study design, study quality, or sample size. All 747
      abstracts presented at the 2004 American Academy of Orthopaedic Surgeons annual
      meeting underwent blinded analysis using previously published criteria. Studies
      that received commercial funding were more likely to conclude with positive
      outcomes. Subspecialty and country of origin were not associated with positive
      outcomes. Commercially funded studies were not more likely than non-funded
      studies to be well-designed. When control groups were used, those in commercially
      funded studies were not larger than those used in nonfunded studies. Our data
      suggest commercial funding was associated with positive outcomes, but we found no
      evidence to suggest commercially funded studies were better designed or larger
      than non-funded studies.

PMID- 17195820
TI  - Immunohistochemical profile of canalicular adenoma of the upper lip: a case
      report.
AB  - Canalicular adenoma is an uncommon benign salivary gland neoplasm that has a
      marked predilection for occurrence in the upper lip. It is composed of columnar
      cells arranged in branching and interconnecting cords of single or double cell
      thick rows. This tumor has an excellent prognosis after conservative surgical
      treatment in all locations. In the present report we describe, using
      immunohistochemistry, the expression of cytokeratins (CK), S-100 protein and EMA
      in a canalicular adenoma that arose in the upper lip of a 55-year-old female.
      Cells of the canalicular adenoma showed an immunohistochemical profile that
      indicates an excretory duct origin: most of these cells positively expressed
      AE1/AE3 cytokeratins and S100 protein. A comparison of the immunohistochemical
      features of canalicular adenoma with other salivary gland neoplasms that share
      similar histological features is discussed.

PMID- 17195819
TI  - Brief ultrasonication improves detection of biofilm-formative bacteria around a
      metal implant.
AB  - Biofilms are complex microenvironments produced by microorganisms on surfaces.
      Ultrasonication disrupts biofilms and may make the microorganism or its DNA
      available for detection. We determined whether ultrasonication could affect our
      ability to detect bacteria adherent to a metal substrate. A biofilm-formative
      Staphylococcus aureus strain was used for an in vitro implant infection model
      (biofilm-formative condition). We used quantitative culture and real time
      polymerase chain reaction to determine the influence of different durations of
      ultrasound on bacterial adherence and viability. Sonication for 1 minute
      increased the yield of bacteria. Sonication longer than 5 minutes led to fewer
      bacterial colonies by conventional culture but not by polymerase chain reaction.
      This suggests short periods of sonication help release bacteria from the metal
      substrate by disrupting the biofilm, but longer periods of sonication lyse
      bacteria prohibiting their detection in microbiologic cultures. A relatively
      short duration of sonication may be desirable for maximizing detection of biofilm
      formative bacteria around implants by culture or polymerase chain reaction.

PMID- 17195821
TI  - Use of nonsteroidal antiinflammatory drugs in dental practice. A review.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) are drugs commonly prescribed in
      dental practice for the management of pain and swelling. Of these substances,
      paracetamol and ibuprofen are the most widely used. Their mechanism of action is
      based on the inhibition of cyclooxygenase, and therefore of prostaglandin
      synthesis. All of these drugs present a similar mechanism of action, as a result
      of which their side effects are also similar. The most frequent range from mild
      (e.g., nausea or vomiting) to serious gastric problems (such as gastric bleeding
      or perforation). Other side effects include an increased risk of vascular
      accidents (particularly acute myocardial infarction), renal toxicity secondary to
      a decrease in perfusion, and the risk of abnormal bleeding tendency due to the
      antiplatelet effect of these drugs. Their use is contraindicated in the third
      trimester of pregnancy, due to the induction of premature ductus arteriosus
      closure. The present study reviews the information currently available on NSAIDs,
      with special emphasis on those aspects related to dental practice.

PMID- 17195823
TI  - Synovial chondromatosis of the temporomandibular joint.
AB  - Synovial Chondromatosis (SC) is a disease whose etiology is unknown, can be
      defined as a benign synovial process characterized by the formation of
      metaplastic cartilaginous nodes inside connective tissue of articular surfaces,
      is considered an active metaplastic phenomenon better than a neoplastic process;
      it presents a greater preference to affect women who constitute almost 70% of
      reported cases, the age range is wide and oscillates between 18-75 years (average
      44.6 years). Between the main clinical findings are: pain, crackle, volume
      augmentation and a limited buccal opening. SC is an unusual state and the reports
      in the English literature are no more than 75 cases, only 66 of those where
      histologically verified, most of those were affecting great joints like hip, knee
      and shoulder, but if SC is not frequent in this sites, is even more infrequent on
      temporomandibular joint. The aim of this paper is to report a clinical case and
      at the same time to realize a brief review of the literature.

PMID- 17195822
TI  - Update on gingival overgrowth by cyclosporine A in renal transplants.
AB  - Severe gingival overgrowth is one of the most frequent side effects in renal
      transplant patients associated with assumption of cyclosporine A. Several
      associations with age, sex, dosage, duration of therapy or interval since
      transplantation have been hypothesized. The introduction of alternative
      immunosuppressant drugs have been suggested to permit better long-term transplant
      outcomes and a decrease in incidence of gingival overgrowth. The aim of the
      present paper is to summarize current knowledge regarding aetiology, pathogenesis
      and management of gingival overgrowth induced by Cyclosporine A.

PMID- 17195824
TI  - Polymorphous low-grade adenocarcinoma of the parotid gland. Case report and
      review of the literature.
AB  - Polymorphous low-grade adenocarcinoma (PLGA) is difficult to diagnose both
      clinically and histologically due to its indolent presentation, and because of
      its morphological diversity that includes several microscopic patterns. The
      aggressive biologic behavior seen in minor salivary glands as compared to major
      glands is apparently associated histologically to a predominance of the papillary
      pattern in the former. Biologic behavior of PLGA in the major salivary glands is
      uncertain, as some cases have developed recurrences and metastases independently
      of the presence of a papillary pattern. A case of PLGA originated de novo in
      parotid gland is presented a 60 year-old male, treatment was surgically excised
      through superficial parotidectomy and to postoperative radiotherapy (46 Gy).
      Forty-eight months later the patient is alive with no signs of recurrence, as
      well as a review of the literature, with particular emphasis in its differential
      diagnosis and biological behavior.

PMID- 17195825
TI  - A large ameloblastic fibro-odontoma of the right mandible.
AB  - The ameloblastic fibro-odontoma is a rare mixed odontogenic tumor. It occurs
      predominantly in children and young adults with no sex predilection and locates
      most often in the posterior segment of the mandible. A painless swelling is the
      most common clinical sign. Radiologically, ameloblastic fibro-odontoma shows a
      circumscribed radiolucency, which contains radio-opaque foci of various sizes and
      shapes. Histological examination reveals a fibrous soft tissue, islands of
      odontogenic epithelium and a disordered mixture of dental tissues. The tumor
      produces enamel or enamel matrix, dentin and cementum. The treatment of
      ameloblastic fibro-odontomas usually consists of enucleation or surgical
      curettage, which is possible due to their benign biological behaviour.

PMID- 17195826
TI  - Effects of diabetes on the osseointegration of dental implants.
AB  - The increased prevalence of diabetes mellitus has become a public health problem.
      Hyperglycaemia entails a rise in the morbidity and mortality of these patients.
      Although a direct relationship with periodontal disease has already been shown,
      little is known about the results of dental implants in diabetics. The present
      paper reviews the bibliography linking the effect of diabetes on the
      osseointegration of implants and the healing of soft tissue. In experimental
      models of diabetes, a reduced level of bone-implant contact has been shown, and
      this can be reversed by means of treatment with insulin. Compared with the
      general population, a higher failure rate is seen in diabetic patients. Most of
      these occur during the first year of functional loading, seemingly pointing to
      the microvascular complications of this condition as a possible causal factor.
      These complications also compromise the healing of soft tissues. It is necessary
      to take certain special considerations into account for the placement of implants
      in diabetic patient. A good control of plasma glycaemia, together with other
      measures, has been shown to improve the percentages of implant survival in these
      patients.

PMID- 17195827
TI  - Papular purpuric gloves and socks syndrome. Presentation of a clinical case.
AB  - Papular-Purpuric Glove-and-Sock Syndrome is a rare, infectious disease, of viral
      etiology, characterized by the presence of pruritus, edema and symmetrical
      erythema, very well defined at the wrists and ankles with a gloves-and-socks
      distribution. Other areas can be affected, with a moderate erythema appearing in
      cheeks, elbows, knees, armpits, abdomen, groin, external genitalia, internal face
      of the thighs and the buttocks. Erosions, small ulcers, enanthema and blisters
      can be observed in the oral cavity and lips, and less frequently in other mucous
      membranes. Complications are rare, although they can be severe, 50% of the
      published cases are related with the Parvovirus B19. Due to its oral involvement
      stomatologists should be aware of this syndrome in order to carry out a correct
      diagnosis of the disease.

PMID- 17195828
TI  - Antimicrobial prophylaxis in oral surgery and dental procedures.
AB  - Transient bacteraemia is a known risk factor following oral surgery and invasive
      dental procedures in patients with altered immune system response and those with
      a susceptible site of infection (patients with heart valve prostheses or recent
      joint replacements, etc.) The most commonly isolated aerobic bacteria in
      postoperative bacteraemia are Streptococcus Viridans. However, other periodontal
      pathogenic anaerobic bacteria are found in up to 64% in blood cultures (mixed
      bacteria or anaerobic bacteria alone). Dental pathogenic bacteria do not appear
      to be covered by standard amoxicillin or clindamycin prophylactic regimens. This
      is partly due to the fact that these anaerobic bacteria often produce beta
      lactamase and also in view of results of antimicrobial sensitivity tests observed
      in recent studies. A personal history of exposure to dental pathogenic bacteria
      may have an impact on the patient s global health, not only because of classical
      local or systemic infectious complications, but also because dental pathogenic
      bacteria have been found in atheromatous plaques in coronary and carotid
      arteries. This finding, along with epidemiological data, suggests that such
      bacteria may contribute to the progression of vascular arteriosclerotic lesions
      and the occurrence of cardiovascular and/or cerebrovascular accidents, although
      the pathogenic mechanisms involved are not yet well known. Taking these facts
      into consideration, and in view of antimicrobial sensitivity data available at
      present, we believe that the use of amoxicillin/clavulanic acid is the most
      appropriate option for prophylaxis of all infectious risks associated with
      bacteraemia of oral origin, due to its broader cover of dental pathogenic
      bacteria and its pharmacokinetic profile.

PMID- 17195829
TI  - Oral leiomyoma in retromolar trigone. A case report.
AB  - Leiomyomas are bening tumours originated on smooth muscle. The most frequent site
      of appearance are uterine myometrium, gastrointestinal tract and skin. The
      highest incidence occurs between 40 and 49 years of age. Its presentation is
      unusual in children or in older patients. Leiomyomas are unfrequent in the oral
      cavity, but in this location are usually localized on tongue, lips and palate.
      Leiomyomas use to appear as well-defined masses, with slow growth and totally
      asymptomatic. Pain is present just in rare cases. The treatment is surgical
      escision. Recurrences are extremely unfrequent. The diagnosis is mainly
      determined by histological studies due to its unspecific clinical appearance.
      Histopathologically proliferation of smooth muscle cells is observad without
      necrotic areas. A low number of mitotic figures can be seen. We present the case
      report of a 25-year old male patient, with a leiomioma on his right retromolar
      trigone. The low incidence of this pathology, the age of the patient and the
      unusual location, make the report of the case worthy.

PMID- 17195830
TI  - Primary leiomyosarcoma of the mandible. A case report.
AB  - The aim of this article is to describe a case of leiomyosarcoma of the mandible
      with immunohistochemical analysis that was useful in making the final diagnosis.
      A 40-year-old woman was referred to the Stomatology Clinic of Sao Paulo Tatuape
      Hospital, for evaluation of a lesion on the left side of the mandible. This
      lesion presented a fast growth in the last 6 months. Intraoral examination showed
      a firm, fixed, red colored mass measuring, approximately 60-mm in diameter. No
      lymph nodes involvement was found. The radiographic examination showed a lytic
      lesion showed ill-demarcated radiolucent with facial and lingual cortical bone
      destruction. Microscopic examination of the mandibular lesion showed a neoplasm
      composed by interlacing fascicles of spindle-shaped cells. Most of the cells
      presented a blut-ended elongated shape. A marked cellular pleomorphism was
      observed, represented by cells with irregular shape and abundant eosinophilic
      cytoplasm. Nuclei were large, hyperchromatic, either vacuoled or cigar-shape. The
      cytoplasm of the cells stained red with Masson s trichrome stain. Neoplastic
      cells expressed vimentin, smooth-muscle actin, HHF-35 and desmin. These findings
      were consistent with the diagnosis of leiomyosarcoma.

PMID- 17195832
TI  - Clinical and radiological course in apicoectomies with the Erbium:YAG laser.
AB  - OBJECTIVE: A study is made of the efficacy of the Erbium:YAG laser in
      granulomatous periapical lesions, based on clinical and radiographic controls.
      MATERIAL AND METHODS: The study comprised a series of 45 patients amenable to
      periapical surgical treatment of incisors, canines and premolars. A conventional
      surgical technique was used, with silver amalgam retrograde filling and
      irradiation of the bone defect and remnant root cement with the Erbium:YAG laser.
      Clinical and radiographic controls were made during 24 months, assessing the
      absence of symptoms and the presence of pain, swelling or fistula and
      ossification of the lesions, respectively. RESULTS: The clinical course proved
      asymptomatic in 95.5% of the cases. As regards remodeling of the bone cavity,
      77.7% had completed ossification after 24 months, 13.3% were in an advanced stage
      of ossification and 4.5% in an intermediate stage, while 4.5% showed treatment
      failure. CONCLUSIONS: The combination of silver amalgam and irradiation with the
      Erbium:YAG laser in periapical surgery showed a very high clinical success rate,
      with a 77.7% bone cavity remodeling rate after 24 months.

PMID- 17195833
TI  - Mandibular involvement of solitary plasmocytoma: a case report.
AB  - Plasma cell neoplasms (multiple myeloma, solitary plasmocytoma of bone and extra
      medullar plasmocytoma) are characterized by a monoclonal neoplastic proliferation
      of plasma cells. Solitary plasmocytoma of bone (SPB) is a localized form of them.
      SPB is most frequently seen in vertebrae and secondarily in long bones. Its
      presence in jaws is extremely rare and when it is seen, angulus and ramus
      mandible are most common sites of occurrence. Prognosis of SPB is worse than
      extra medullar plasmacytoma (EMP) and approximately 50% of SPB will transform to
      multiple myelom. A 76-year old woman consulted to our clinic with a chief
      complaint of slowly developed swelling in her mandible. She had an operation from
      caput femur because of plasmocytoma two months before. Panoramic radiography
      revealed a radiolucent lesion in the mandibular anterior region, 60x35 mm in
      dimension. Aspiration biopsy was performed and histopathological examination was
      reported as plasmocytoma. She was referred to the oncology department for
      treatment but died before the treatment finished.

PMID- 17195831
TI  - Evaluation of lidocaine and mepivacaine for inferior third molar surgery.
AB  - OBJECTIVE: The aim of this study was to compare 2% lidocaine and 2% mepivacaine
      with 1:100,000 epinephrine for postoperative pain control. STUDY DESIGN: A group
      of 35 patients, both genders were recruited, whose had ages ranged from 13 to 27
      years-old and had two inferior third molars in similar positions to be extracted.
      The cartridges were distributed to the patients according to a randomised
      pattern, where lidocaine was in the control group and mepivacaine in the
      experimental group. RESULTS: Results showed no significant association between
      the anesthetics and postoperative pain, pulp sensibility after one hour, gender,
      tooth position and duration of the surgical procedure. CONCLUSIONS: It was shown
      that lidocaine and mepivacaine have similar time of anesthesia, they are adequate
      for surgical procedures that last one hour, and there was no difference between
      the two anesthetics in relation to the severety of post-operative pain.

PMID- 17195835
TI  - Mandibular ameloblastoma. Reconstruction with iliac crest graft and implants.
AB  - The ameloblastoma is a bening odontogenic tumor. The treatment planning in young
      persons is still not clear. We describe a case report of a young boy who was
      treated in our unit and we review the different approaches for this type of
      lesions, which nowadays still not clear in this patients.

PMID- 17195836
TI  - Subcutaneous emphysema secondary to dental treatment: case report.
AB  - Subcutaneous emphysema is a relatively rare complication of dental treatment,
      although increasingly due to the use of high pressure air instruments. Many cases
      go unrecognized or are misdiagnosed. Majority of patients with this complication
      resolve spontaneously after 5 to 10 days, however some can advance to potentially
      life-threatening complications. A case of subcutaneous emphysema during
      restorative procedure in a 52-year-old woman was treated in the Docent
      Odontological Clinic of the Frontera University is presented. The differential
      diagnosis and management of this condition is discussed. Our purpose is not to
      add one more case of emphysema to literature, but to show dentists that in simple
      restorative procedures using air pressure instruments, they could be exposed to
      this complication.

PMID- 17195834
TI  - Iatrogenic mandibular fracture associated with third molar removal. Can it be
      prevented?
AB  - Removal of third molars is the most common procedure in oral surgery. It may be
      associated with complications, such as sensory damage , dry socket, infection and
      iatrogenic damage. A case of mandibular angle fracture during third molar
      extraction in a 37-year-old female is reported. Literature review on the possible
      etiologies and ways of prevention were recorded. The reason is believed to be
      multifactorial and include: age, gender, degree of impaction, relative volume of
      the tooth in the jaw, preexisting infection or bone lesions, failure to maintain
      a soft diet in the early postoperative period and the surgical technique. It is
      possible to reduce the risk of this complication by adoption of preventive
      measures.

PMID- 17195837
TI  - Control of Frey's syndrome in patients treated with botulinum toxin type A.
AB  - AIM: To identify the severity of Frey s syndrome and its response to botulinum
      toxin type A. METHODS: Minor test was performed in all cases to assess the extent
      of the affected area, using the contralateral side as control. Severity was
      assessed according to the proposal of Luna-Ortiz et al. Response was evaluated
      after 3 and 6 months, and was compared with the basal data. RESULTS: Frey s
      syndrome was documented in 38 patients, but only 23 cases accepted the botulinum
      toxin type A treatment. Severity was moderate in 8 (35%) and severe in 15 (65%)
      cases. Mean applied dose was 1.41 MU/cm2 in 21 patients (91%), whereas one
      patient was treated with 10 MU for a 0.8 cm2 affected area (12.5 MU/cm2) and
      another patient with 10 MU for a 0.5 cm2 affected area (20 MU/cm2) due to
      severity of their symptomatology. Average affected area at the beginning was 14.2
      cm2, while after 3 and 6 months of treatment it was 4.1 cm2 and 4.4 cm2
      respectively (p<0.001). The two patients that received higher doses of botulinum
      toxin A had complete response. Complete response was observed in 13 patients
      (56.5%) at 3 months, but in only nine (39%) this lack of symptomatology persisted
      at 6 months. In three cases (13%) no response was obtained at 3 months, and the
      application of an additional dose of botulinum toxin type A produced no response
      in two of them after 6 months. Comparison of the severity score of the average
      basal value vs. that obtained at 3 and 6 months revealed a significant difference
      (p<0.05); however, no statistically significant difference was found when
      comparing outcome at 3 vs. 6 months. There were no statistically significant
      differences using the independent samples test when comparing outcome after
      treatment in relation to gender, type of surgery, or use of postoperative
      radiation therapy (p>0.05). In conclusion, botulinum toxin A remains as the
      treatment of choice for Frey s syndrome.

PMID- 17195838
TI  - A novel human primary immunodeficiency syndrome caused by deficiency of the
      endosomal adaptor protein p14.
AB  - Lysosome-related organelles have versatile functions, including protein and lipid
      degradation, signal transduction and protein secretion. The molecular elucidation
      of rare congenital diseases affecting endosomal-lysosomal biogenesis has given
      insights into physiological functions of the innate and adaptive immune system.
      Here, we describe a previously unknown human primary immunodeficiency disorder
      and provide evidence that the endosomal adaptor protein p14, previously
      characterized as confining mitogen-activated protein kinase (MAPK) signaling to
      late endosomes, is crucial for the function of neutrophils, B cells, cytotoxic T
      cells and melanocytes. Combining genetic linkage studies and transcriptional
      profiling analysis, we identified a homozygous point mutation in the 3'
      untranslated region (UTR) of p14 (also known as MAPBPIP), resulting in decreased
      protein expression. In p14-deficient cells, the distribution of late endosomes
      was severely perturbed, suggesting a previously unknown role for p14 in endosomal
      biogenesis. These findings have implications for understanding endosomal membrane
      dynamics, compartmentalization of cell signal cascades, and their role in
      immunity.

PMID- 17195839
TI  - Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells
      and Stat3 signaling in obese animals.
AB  - Metabolic hormones, such as leptin, alter the input organization of hypothalamic
      circuits, resulting in increased pro-opiomelanocortin (POMC) tone, followed by
      decreased food intake and adiposity. The gonadal steroid estradiol can also
      reduce appetite and adiposity, and it influences synaptic plasticity. Here we
      report that estradiol (E2) triggers a robust increase in the number of excitatory
      inputs to POMC neurons in the arcuate nucleus of wild-type rats and mice. This
      rearrangement of synapses in the arcuate nucleus is leptin independent because it
      also occurred in leptin-deficient (ob/ob) and leptin receptor-deficient (db/db)
      mice, and was paralleled by decreased food intake and body weight gain as well as
      increased energy expenditure. However, estrogen-induced decrease in body weight
      was dependent on Stat3 activation in the brain. These observations support the
      notion that synaptic plasticity of arcuate nucleus feeding circuits is an
      inherent element in body weight regulation and offer alternative approaches to
      reducing adiposity under conditions of failed leptin receptor signaling.

PMID- 17195840
TI  - Computational prediction of proteotypic peptides for quantitative proteomics.
AB  - Mass spectrometry-based quantitative proteomics has become an important component
      of biological and clinical research. Although such analyses typically assume that
      a protein's peptide fragments are observed with equal likelihood, only a few so
      called 'proteotypic' peptides are repeatedly and consistently identified for any
      given protein present in a mixture. Using >600,000 peptide identifications
      generated by four proteomic platforms, we empirically identified >16,000
      proteotypic peptides for 4,030 distinct yeast proteins. Characteristic
      physicochemical properties of these peptides were used to develop a computational
      tool that can predict proteotypic peptides for any protein from any organism, for
      a given platform, with >85% cumulative accuracy. Possible applications of
      proteotypic peptides include validation of protein identifications, absolute
      quantification of proteins, annotation of coding sequences in genomes, and
      characterization of the physical principles governing key elements of mass
      spectrometric workflows (e.g., digestion, chromatography, ionization and
      fragmentation).

PMID- 17195841
TI  - Production of cattle lacking prion protein.
AB  - Prion diseases are caused by propagation of misfolded forms of the normal
      cellular prion protein PrP(C), such as PrP(BSE) in bovine spongiform
      encephalopathy (BSE) in cattle and PrP(CJD) in Creutzfeldt-Jakob disease (CJD) in
      humans. Disruption of PrP(C) expression in mice, a species that does not
      naturally contract prion diseases, results in no apparent developmental
      abnormalities. However, the impact of ablating PrP(C) function in natural host
      species of prion diseases is unknown. Here we report the generation and
      characterization of PrP(C)-deficient cattle produced by a sequential gene
      targeting system. At over 20 months of age, the cattle are clinically,
      physiologically, histopathologically, immunologically and reproductively normal.
      Brain tissue homogenates are resistant to prion propagation in vitro as assessed
      by protein misfolding cyclic amplification. PrP(C)-deficient cattle may be a
      useful model for prion research and could provide industrial bovine products free
      of prion proteins.

PMID- 17195842
TI  - Spatiotopic selectivity of BOLD responses to visual motion in human area MT.
AB  - Many neurons in the monkey visual extrastriate cortex have receptive fields that
      are affected by gaze direction. In humans, psychophysical studies suggest that
      motion signals may be encoded in a spatiotopic fashion. Here we use functional
      magnetic resonance imaging to study spatial selectivity in the human middle
      temporal cortex (area MT or V5), an area that is clearly implicated in motion
      perception. The results show that the response of MT is modulated by gaze
      direction, generating a spatial selectivity based on screen rather than retinal
      coordinates. This area could be the neurophysiological substrate of the
      spatiotopic representation of motion signals.

PMID- 17195843
TI  - Spatial relational learning persists following neonatal hippocampal lesions in
      macaque monkeys.
AB  - The hippocampus is important for the acquisition of spatial representations of
      the environment and consequently in contextual memory. This suggests that the
      neural substrates underlying spatial cognition might be essential for remembering
      specific life episodes. Indeed, hippocampal lesions prevent spatial relational
      learning in adult rodents and monkeys, and result in profound amnesia in adult
      humans. In contrast, we show here that monkeys with neonatal hippocampal lesions
      learned new spatial relational information. Our experiments suggest that early
      hippocampal damage leads to functional brain reorganization that enables spatial
      information to be acquired through the use of brain regions that normally do not
      subserve this function.

PMID- 17195844
TI  - Peripheral antigen display by lymph node stroma promotes T cell tolerance to
      intestinal self.
AB  - The intestinal epithelium functions to absorb nutrients and to protect the
      organism against microbes. To prevent autoimmune attack on this vital tissue, T
      cell tolerance to intestinal self-antigens must be established. Central tolerance
      mechanisms involve medullary thymic epithelial cells (mTECs), which use
      endogenously expressed peripheral-tissue antigens (PTAs) to delete self-reactive
      thymocytes. The prevailing model for the induction of peripheral tolerance
      involves cross-presentation of tissue antigens by quiescent dendritic cells. Here
      we show that lymph node stromal cells present endogenously expressed PTAs to T
      cells. Moreover, antigen presentation by lymph node stroma is sufficient to
      induce primary activation and subsequent tolerance among CD8(+) T cells. Thus,
      lymph node stromal cells are functionally akin to mTECs and provide a direct
      strategy for purging the peripheral repertoire of self-reactive T cells.

PMID- 17195845
TI  - Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4
      in T helper type 1 cells.
AB  - Cell differentiation involves activation and silencing of lineage-specific genes.
      Here we show that the transcription factor Runx3 is induced in T helper type 1
      (T(H)1) cells in a T-bet-dependent manner, and that both transcription factors T
      bet and Runx3 are required for maximal production of interferon-gamma (IFN-gamma)
      and silencing of the gene encoding interleukin 4 (Il4) in T(H)1 cells. T-bet does
      not repress Il4 in Runx3-deficient T(H)2 cells, but coexpression of Runx3 and T
      bet induces potent repression in those cells. Both T-bet and Runx3 bind to the
      Ifng promoter and the Il4 silencer, and deletion of the silencer decreases the
      sensitivity of Il4 to repression by either factor. Our data indicate that
      cytokine gene expression in T(H)1 cells may be controlled by a feed-forward
      regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to
      direct lineage-specific gene activation and silencing.

PMID- 17195846
TI  - Optical induction of synaptic plasticity using a light-sensitive channel.
AB  - We have combined millisecond activation of channelrhodopsin-2 (ChR2), a light
      gated ion channel, with two-photon calcium imaging to investigate active synaptic
      contacts in rat hippocampal slice cultures. Calcium influx was larger during
      light-induced action potentials than during action potentials induced by somatic
      current injection, leading to highly reproducible synaptic transmission. Pairing
      of light stimulation with postsynaptic depolarization induced long-term
      potentiation, making this technique ideal for genetic and pharmacological
      dissection of synaptic plasticity.

PMID- 17195847
TI  - Nucleotide recognition by the cytoplasmic domain of the human chloride
      transporter ClC-5.
AB  - The ubiquitous CBS domains, which are found as part of cytoplasmic domains in the
      ClC family of chloride channels and transporters, have previously been identified
      as building blocks for regulatory nucleotide-binding sites. Here we report the
      structures of the cytoplasmic domain of the human transporter ClC-5 in complex
      with ATP and ADP. The nucleotides bind to a specific site in the protein. As
      determined by equilibrium dialysis, the affinities for ATP, ADP and AMP are in
      the high micromolar range. Point mutations that interfere with nucleotide binding
      change the transport behavior of a ClC-5 mutant expressed in Xenopus laevis
      oocytes. Our results establish the structural and energetic basis for the
      interaction of ClC-5 with nucleotides and provide a framework for future
      investigations.

PMID- 17195848
TI  - The Ndc80/HEC1 complex is a contact point for kinetochore-microtubule attachment.
AB  - Kinetochores are multicomponent assemblies that connect chromosomal centromeres
      to mitotic-spindle microtubules. The Ndc80 complex is an essential core element
      of kinetochores, conserved from yeast to humans. It is a rod-like assembly of
      four proteins- Ndc80p (HEC1 in humans), Nuf2p, Spc24p and Spc25p. We describe
      here the crystal structure of the most conserved region of HEC1, which lies at
      one end of the rod and near the N terminus of the polypeptide chain. It folds
      into a calponin-homology domain, resembling the microtubule-binding domain of the
      plus-end-associated protein EB1. We show that an Ndc80p-Nuf2p heterodimer binds
      microtubules in vitro. The less conserved, N-terminal segment of Ndc80p
      contributes to the interaction and may be a crucial regulatory element. We
      propose that the Ndc80 complex forms a direct link between kinetochore core
      components and spindle microtubules.

PMID- 17195849
TI  - Selective inhibitors of death in mutant huntingtin cells.
AB  - Huntington disease (HD) is an inherited neurodegenerative disorder with unclear
      pathophysiology. We developed a high-throughput assay in a neuronal cell culture
      model of HD, screened 43,685 compounds and identified 29 novel selective
      inhibitors of cell death in mutant huntingtin-expressing cells. Four compounds
      were active in diverse HD models, which suggests a role for cell death in HD;
      these compounds are mechanistic probes and potential drug leads for HD.

PMID- 17195850
TI  - Work-related bystander deaths in New Zealand: a significant hidden problem.
AB  - OBJECTIVES: To estimate the extent of bystander work-related traffic fatal injury
      for New Zealand as well as the contribution of all bystander events to the total
      burden of work-related fatal traffic injury and work-related fatal injury in
      general. METHODS: Potential cases were identified from national administrative
      databases. The circumstances of the deaths in each incident were reviewed
      directly from coronial files to determine work-relatedness. RESULTS: For 1985
      1998 we identified 1447 people whose death was associated with another person's
      work activity on a public road and who were not working at the time. This
      compares with 241 "working" and 192 "commuting" deaths on a public road for the
      same period. Bystanders thus represented approximately 75% of the work-related
      fatal traffic crash injury problem. We estimate that (on average) approximately
      115 bystanders were killed each year and this represents approximately 52% of the
      total work-related fatality problem. CONCLUSIONS: Work-related bystander deaths
      are a major contributor to work-related injury in New Zealand, the majority
      occurring in the context of road traffic crashes. These deaths deserve more
      attention than they have received to date.

PMID- 17195851
TI  - Characteristics of general practitioner consultations prior to suicide: a nested
      case-control study in New Zealand.
AB  - AIM: To examine characteristics of general practice consultations in a New
      Zealand primary care population of patients who died by suicide. METHODS: Case
      control study design, with data linkage between the RNZCGP Research Unit
      Database, the National Mortality Database and the Hospital Separation Diagnosis
      Database (hospital discharges) from 1996 to 2001. The cases were suicides who had
      attended a general practice contributing data to the Research Unit database. Each
      case was matched by gender and age to three randomly selected patients from the
      Research Unit database. RESULTS: There were 221 cases of suicide identified, of
      which 60% had a general practice consultation in the 6 months prior to death. The
      significant exposure variables, corrected OR (95% CI) in the multivariate
      analysis were: any previous hospital admission (between January 1996 and date of
      death) for a psychiatric condition, 23.75 (9.01 to 62.63); any notation in the
      general practice record of depression, suicidal ideation or self-harm, 14.97
      (4.61 to 48.65); previous hospital admission with self-harm, 8.39 (1.73 to
      40.65); and general practice prescription of sedatives, 4.34 (1.69 to 11.10).
      CONCLUSIONS: In general, general practice patients who commit suicide have higher
      rates of depression, suicidal ideation, previous self harm, and sedative
      prescription than average.

PMID- 17195852
TI  - Injuries to New Zealanders participating in adventure tourism and adventure
      sports: an analysis of Accident Compensation Corporation (ACC) claims.
AB  - AIMS: The aim of this study was to examine the involvement of adventure tourism
      and adventure sports activity in injury claims made to the Accident Compensation
      Corporation (ACC). METHODS: Epidemiological analysis of ACC claims for the
      period, July 2004 to June 2005, where adventure activities were involved in the
      injury. RESULTS: 18,697 adventure tourism and adventure sports injury claims were
      identified from the data, representing 28 activity sectors. Injuries were most
      common during the summer months, and were most frequently located in the major
      population centres. The majority of injuries were incurred by claimants in the 20
      50 years age groups, although claimants over 50 years of age had highest claims
      costs. Males incurred 60% of all claims. Four activities (horse riding, mountain
      biking, tramping/hiking, and surfing) were responsible for approximately 60% of
      all adventure tourism and adventure sports-related injuries. Slips, trips, and
      falls were the most common injury initiating events, and injuries were most often
      to the back/spine, shoulder, and knee. CONCLUSIONS: These findings suggest the
      need to investigate whether regulatory intervention in the form of codes of
      practice for high injury count activities such as horse riding and mountain
      biking may be necessary. Health promotion messages and education programs should
      focus on these and other high-injury risk areas. Improved risk management
      practices are required for commercial adventure tourism and adventure sports
      operators in New Zealand if safety is to be improved across this sector.

PMID- 17195853
TI  - The case for a New Zealand acute care strategy.
AB  - People are coming to harm due to deficiencies in the provision of both elective
      and acute care. New Zealand cannot provide care to all who might benefit, but it
      behoves us to use whatever resource we can afford to its maximum utility. Acute
      and elective patients share the same resource, and the overwhelming of the acute
      services is causing both acute and elective patients to suffer. To fix this
      requires that DHBs know how to, are able to, and want to fix the problem. To
      muster the knowledge and the ability, and to encourage the desire, we need a
      national acute care strategy. Consideration of three conceptual models gives us
      six principles guiding solutions to the problems in acute care provision.
      Combining these principles with meaningful performance measures and with strong
      incentives to perform, will form the basis of an acute care strategy.

PMID- 17195854
TI  - General practitioners' attitudes toward (and use of) complementary and
      alternative medicine: a New Zealand nationwide survey.
AB  - AIMS: This study aimed to update our understanding of how general practitioners
      view and use complementary and alternative medicine (CAM). METHOD: A nationwide
      cross-sectional postal questionnaire sent to 500 randomly selected general
      practitioners (GPs) of the 2358 who met the inclusion criteria of the study in
      December 2005. RESULTS: 300 completed questionnaires were returned thus giving a
      response rate of 60%. Twenty percent of the GP respondents practiced (and 95%
      referred patients to) one or more forms of complementary and alternative
      medicine. The most common CAM therapy practiced by GPs was acupuncture, and
      chiropractic manipulation was the most common GP-referred therapy for patients.
      Thirty-two percent of respondents had formal training and 29% had self education
      in one or more CAM therapies. Sixty-seven percent felt that an overview of CAM
      should be included in conventional medical education. CONCLUSIONS: The number of
      GPs practising CAM therapies has decreased over the past 15 years, although the
      number referring patients to CAM has increased. The finding 'that GPs feel
      information about CAM should be included in medical education' is consistent with
      earlier research and should be taken into account when developing the medical
      curriculum.

PMID- 17195855
TI  - Small bowel strangulation caused by delayed penetrating diaphragmatic hernia.

PMID- 17195856
TI  - Medical image. Metastatic Crohn's disease.

PMID- 17195857
TI  - Basic science confidence in senior medical students from the University of
      Auckland, New Zealand: results of the 2005 Senior Students Survey.
AB  - AIMS: To determine the proportion of senior medical students who feel their
      knowledge of the basic sciences is adequate for safe medical practice. DESIGN:
      Cross-sectional survey. Twenty-five point questionnaire. Likert scale response
      ranking. SETTING: University of Auckland School of Medicine, Auckland, New
      Zealand. PARTICIPANTS: 218 surveys were emailed to functioning addresses of
      fourth and fifth year students. 156 students emailed responses (71.60% response
      rate), comprising 55% of the total fourth and fifth year student population.
      RESULTS: Thirty-three percent of respondents (95% CI 0.26-0.41) felt their
      knowledge of anatomy was adequate. Seventeen percent (95% CI 0.12-0.24) of
      students felt their knowledge of pharmacology was adequate. Fifty-six percent
      (95% CI 0.48-0.64) of all respondents felt their knowledge of physiology was
      adequate. Forty-six percent (95% CI 0.38-0.54) of all respondents felt their
      knowledge of pathology was adequate Seventy-six percent (95% CI 0.69-0.83) felt
      their behavioural science knowledge was adequate. A greater proportion of
      respondents were confident in behavioural science than any other basic science
      (p<0.01). CONCLUSION: Respondents to the 2005 senior medical students survey from
      the University of Auckland School of Medicine are most confident in their
      behavioural sciences knowledge. Respondents are least confident in their
      knowledge of pharmacology.

PMID- 17195858
TI  - SIDS-protective infant care practices among Auckland, New Zealand mothers.
AB  - AIM: To survey the knowledge and implementation of sudden infant death syndrome
      (SIDS)-protective infant care practices in mothers of infants aged less than 4
      months. METHODS: A postal survey was carried out of knowledge of SIDS risk
      factors and infant care practices of 200 mothers with infants aged 6-8 weeks and
      3-4 months. RESULTS: Mothers who could cite supine sleeping as protective
      comprised 84%, while 73% knew that smoking was a risk factor. Fewer knew that
      room sharing, keeping the face clear of bedding, and avoiding bed sharing and
      overheating are also protective. Fifty-four percent of the infants usually room
      share with a parent, while 39% both room-share and sleep in their own bed.
      Sixteen percent usually co-slept for part or all of the night. Nearly one-third
      used pacifiers. Mothers who smoked during pregnancy comprised 8%, while 7% had
      smoked in the last 24 hours. Most infants (97%) had been breastfed at some time.
      CONCLUSIONS: Maternal education of the benefits of supine sleeping, not smoking,
      and breastfeeding appear well understood by these mothers. However, more
      education is needed about other SIDS-protective behaviours such as keeping the
      face clear and sleeping the infant in their own bed in the parents' room.

PMID- 17195859
TI  - Necrotizing fasciitis after the post partum diastasis of the symphysis pubis.

PMID- 17195860
TI  - Adventure sports in New Zealand: dangerous and costly recklessness or valuable
      health-promoting activity? Be careful to judge.

PMID- 17195861
TI  - Cigarette pack covers (of health warnings) and the public good.

PMID- 17195862
TI  - Redefinition of the metabolic syndrome--useful or creating illness?

PMID- 17195863
TI  - New Zealand workforce issues.

PMID- 17195865
TI  - Adiabatic quantum computing with phase modulated laser pulses.
AB  - Implementation of quantum logical gates for multilevel systems is demonstrated
      through decoherence control under the quantum adiabatic method using simple phase
      modulated laser pulses. We make use of selective population inversion and
      Hamiltonian evolution with time to achieve such goals robustly instead of the
      standard unitary transformation language.

PMID- 17195864
TI  - Rapid, depth-resolved light scattering measurements using Fourier domain, angle
      resolved low coherence interferometry.
AB  - We present a novel angle-resolved low coherence interferometry scheme for rapid
      measurement of depth-resolved angular scattering distributions to enable
      determination of scatterer size via elastic scattering properties. Depth
      resolution is achieved using a superluminescent diode in a modified Mach-Zehnder
      interferometer with the mixed signal and reference fields dispersed by an imaging
      spectrograph. The spectrograph slit is located in a Fourier transform plane of
      the scattering sample, enabling angle-resolved measurements over a 0.21 radian
      range. The capabilities of the new technique are demonstrated by recording the
      distribution of light scattered by a sub-surface layer of polystyrene
      microspheres in 40 milliseconds. The data are used to determine the microsphere
      size with good accuracy. Future clinical application to measuring the size of
      cell nuclei in living epithelial tissues using backscattered light is discussed.

PMID- 17195866
TI  - Smoking patterns among primary school students in Turkey.
AB  - Cigarette smoking continues to be a threat to global health. The number of
      cigarettes smoked per person tends to increase each year, and the age of starting
      seems to be dropping. The research related to cigarette smoking conducted among
      young people generally studied high school or university students. However,
      studies have shown that students usually start smoking during the primary school
      period out of curiosity or imitation. The purpose of the present study was to
      find the prevalence of cigarette smoking among primary school students and the
      reasons for starting smoking, and to determine the characteristics of cigarette
      smoking of their parents. This study was conducted among 17 primary schools
      chosen according to their socioeconomic situations in different municipality
      districts in Turkey, with 9,408 students participating. Data were obtained by
      questionnaire. The mean age to start smoking was 11.7 +/- 1.6; 82.9% of the
      students who took part in this study had never smoked before, 13.4% had tried
      smoking at least once, and 3.7% had been smoking regularly. The biggest reason
      for smoking was just curiosity or imitation. It was determined that a risk factor
      for students to start smoking was parents who smoke. The 17% smoking rate among
      primary school students was high in our opinion and prevention studies initiated.
      In addition, the effects of cigarette-smoking parents on students who start
      smoking should also be considered.

PMID- 17195867
TI  - The origin of individual differences in the course and severity of diseases.
AB  - Any disease manifests itself individually either by a bright or restricted
      spectrum of clinical signs and resultant clinical courses that range from
      asymptomatic to deadly, from acute to chronic, etc. Until recently, the origin of
      this kind of biodiversity was poorly investigated and understood, but advances in
      immunology--especially in identifying constitutional (genetic) mechanisms of
      immunity--have contributed to our understanding of the origin of individual
      diversity in diseases. Any disease destroys only focal areas in the affected
      organisms, and the amounts, sizes, and distribution of such focal lesions vary
      from patient to patient. In a population predilected to a relevant pathogenic
      agent, individuals can be conveniently divided into three categories: totally
      resistant organisms that contain no susceptible structures and are not affected;
      mildly susceptible organisms in which a few foci appear and in which the disease
      runs a benign course; organisms in which the number of constitutionally
      susceptible structures is high and the disease develops in a severe form. The
      diversity is formed by the mating of genetically different parents that
      determines the differences in susceptibility of genetically various parts of the
      descendant organism.

PMID- 17195869
TI  - Youth knowledge of physical activity health benefits: a Brazilian case study.
AB  - This study presents the findings of a questionnaire-based investigation of
      knowledge about the relationship of physical activity to health among adolescent
      participants of a community-based physical activity intervention program in Sao
      Paulo, Brazil. Qualitative (inductive content analysis) and quantitative methods
      were applied to examine the participants' responses to two open-ended questions
      concerning the health benefits of physical activity and the educational goals of
      the intervention. More than 75% of all participants stated that health benefits
      (of some type) are attained through participation in physical activity. More than
      50% of participants reported that the goal of the intervention was to educate
      people about the importance of a healthy, active lifestyle. Adolescents
      understand the relationship of physical activity to health as reflected in their
      knowledge assessments; their lifestyle choices support these beliefs. These
      findings offer encouragement for the development and implementation of
      educationally oriented interventions aimed at providing physical activity
      information and programming.

PMID- 17195870
TI  - Genetics of malignant hyperthermia.
AB  - Study of the genetics of the malignant hyperthermia syndrome began in families in
      which both malignant hyperthermia (MH) episodes had been experienced and
      individuals had strongly positive contracture tests diagnostic of susceptibility
      to MH. Linkage studies associated this MH phenotype to the ryanodine receptor
      gene (RYR1) at chromosome 19q13.1 in many families. Although the MH phenotype is
      not always linked to chromosome 19, the RYR1 has remained the focus of
      experimentation. Other candidate genes exist, but few MH-susceptible families
      have variants of these genes. Hundreds of MH-susceptible people have variants of
      RYR1.

PMID- 17195871
TI  - Pharmaceutical compounds in wastewater: wetland treatment as a potential
      solution.
AB  - Pharmaceutical compounds are being released into the aquatic environment through
      wastewater discharge around the globe. While there is limited removal of these
      compounds within wastewater treatment plants, wetland treatment might prove to be
      an effective means to reduce the discharge of the compounds into the environment.
      Wetlands can promote removal of these pharmaceutical compounds through a number
      of mechanisms including photolysis, plant uptake, microbial degradation, and
      sorption to the soil. We review relevant laboratory research on these various
      mechanisms and provide data on the few studies that have examined wetland
      removal. There is a need to document the degree to which various pharmaceutical
      compounds are removed in full-scale treatment wetlands, as there is a paucity of
      data on overall pharmaceutical removal rates.

PMID- 17195868
TI  - The antiapoptotic RBM5/LUCA-15/H37 gene and its role in apoptosis and human
      cancer: research update.
AB  - The candidate tumour-suppressor gene, LUCA-15/RBM5/H37, maps to the lung cancer
      tumour-suppressor locus 3p21.3. The LUCA-15 gene locus encodes at least four
      alternatively spliced transcripts that have been shown to function as regulators
      of apoptosis, a fact which may have major significance in tumour regulation. This
      review highlights recent evidence that further implicates the LUCA-15 locus in
      the control of apoptosis and cell proliferation, and focuses on the observations
      that confirm the tumour-suppressor activity of this gene.

PMID- 17195872
TI  - The digestive system and nutritional considerations for individuals with Rett
      syndrome.
AB  - Rett syndrome (RS) is a neurodevelopmental syndrome of genetic origin that mainly
      affects females. Individuals diagnosed with RS exhibit a variety of functional
      difficulties that impair their quality of life. One of the affected systems is
      the digestive system, where 74% of persons with RS have abnormal functioning. The
      affected digestive system causes this population to present an array of problems,
      such as gastroesophageal reflux (GER), constipation, and malnutrition, leading to
      failure to thrive (FTT), which resolves in reduced functional ability. Due to the
      severe effects of the dysfunctional digestive system of individuals with RS, this
      article will describe the problems common to this population, as well as propose
      some clinical suggestions for intervention.

PMID- 17195873
TI  - Mode of glucocorticoid actions in airway disease.
AB  - Synthetic glucocorticoids are the most potent anti-inflammatory agents used to
      treat chronic inflammatory disease, such as asthma. However, a small number (<5%)
      of asthmatic patients and almost all patients with chronic obstructive pulmonary
      disease (COPD) do not respond well, or at all, to glucocorticoid therapy. If the
      molecular mechanism of glucocorticoid insensitivity is uncovered, it may in turn
      provide insight into the key mechanism of glucocorticoid action and allow a
      rational way to implement treatment regimens that restore glucocorticoid
      sensitivity. Glucocorticoids exert their effects by binding to a cytoplasmic
      glucocorticoid receptor (GR), which is subjected to post-translational
      modifications. Receptor phosphorylation, acetylation, nitrosylation,
      ubiquitinylation, and other modifications influence hormone binding, nuclear
      translocation, and protein half-life. Analysis of GR interactions to other
      molecules, such as coactivators or corepressors, may explain the genetic
      specificity of GR action. Priming with inflammatory cytokine or
      oxidative/nitrative stress is a mechanism for the glucocorticoid resistance
      observed in chronic inflammatory airway disease via reduction of corepressors or
      GR modification. Therapies targeting these aspects of the GR activation pathway
      may reverse glucocorticoid resistance in patients with glucocorticoid-insensitive
      airway disease and some patients with other inflammatory diseases, such as
      rheumatoid arthritis and inflammatory bowel disease.

PMID- 17195874
TI  - Peroxisome proliferator-activated receptors and shock state.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors that are
      related to retinoid, steroid, and thyroid hormone receptors. Three isotypes of
      PPARs have been identified: alpha, beta/delta, and gamma, encoded by different
      genes and distributed in various tissues. PPARs are implicated in the control of
      inflammatory responses and in energy homeostasis and, thus, can be defined as
      metabolic and anti-inflammatory transcription factors. They exert anti
      inflammatory effects by inhibiting the induction of proinflammatory cytokines,
      adhesion molecules, and extracellular matrix proteins, or by stimulating the
      production of anti-inflammatory molecules. Moreover, PPARs modulate the
      proliferation, differentiation, and survival of immune cells. This review
      presents the current state of knowledge regarding the involvement of PPARs in the
      control of inflammatory response, and their potential therapeutic applications in
      several types of shock, as well as hemorrhagic, septic, and nonseptic shock.

PMID- 17195875
TI  - Early contact stage of apoptosis: its morphological features and function.
AB  - Apoptosis has been a biological phenomenon of intense interest for 20 years, but
      the earlier morphological features of apoptosis have not been determined
      hitherto. Using the methods of semi- and ultrathin sections, the livers of intact
      embryos and young rats have been studied under the effect of cycloheximide to
      determine morphological features of an early stage of apoptosis. It is discovered
      that both in hepatoblasts and hepatocytes, apoptosis, besides the well-known
      stages, also includes an early contact stage, distinguishing features of which
      are agglutination of bound ribosomes (breaking of translation), elimination of
      the nucleolus, reduction of free polysomes (and in hepatocytes, reduction of
      cisterns of rough endoplasmic reticulum), formation of cytoplasmic excrescences,
      and cell shape changes. The early stage of apoptosis is characterized by close
      contact with neighboring cells. At a certain phase of the contact stage of
      apoptosis, the nucleolus reappears in the nucleus and the number of free
      polysomes in the cytoplasm increases, which suggests the renewal of synthesis of
      new RNA and proteins. Close contact of differentiating and mitotic hepatoblasts
      with apoptotic cells indicates a certain functional relationship between these
      cells that is realized not only by micropinocytosis, but through gap junctions as
      well. We assume that the apoptotic cell, besides proteolytic products, can
      contain newly synthesized, low-molecular substances, the relocation of which from
      apoptotic to neighboring cells may contribute to both functional activity and
      proliferation of adjacent hepatoblasts and, therefore, the function of apoptosis
      may not be limited only to the elimination of harmful, damaged, and unwanted
      cells.

PMID- 17195876
TI  - Interlimb transfer of grasp orientation is asymmetrical.
AB  - One the most fundamental aspects of the human motor system is the hemispheric
      asymmetry seen in behavioral specialization. Hemispheric dominance can be
      inferred by a contralateral hand preference in grasping. Few studies have
      considered grasp orientation in the context of manual lateralization and none has
      looked at grasp orientation with natural prehension. Thirty right-handed adults
      performed precision grasps of a cylinder using the thumb and index fingers, and
      the opposition axis (OA) was defined as the line connecting these two contact
      points on the cylinder. Subjects made ten consecutive grasps with one hand
      (primary hand movements) followed by ten grasps with the other hand (trailing
      movements). Differences between primary and trailing grasps revealed that each
      hemisphere is capable of programming the orientation of the OA and that primary
      movements with the right hand significantly influenced OA orientation of the
      trailing left hand. These results extend the hemispheric dominance of the left
      hemisphere to the final positions of fingers during prehension.

PMID- 17195877
TI  - Perceived parental monitoring and health risk behavior among public secondary
      school students in El Salvador.
AB  - Although parental monitoring has received considerable attention in studies of
      U.S. adolescents, few published studies have examined how parents' knowledge of
      their children's whereabouts may influence health risk behaviors in adolescents
      living in Latin America. We investigated the association between perceived
      parental monitoring and substance use, fighting, and sexual behaviors in rural
      and urban Salvadoran adolescents (n = 982). After adjusting for several
      sociodemographic covariates, multilevel regression analyses indicated that
      students reporting low parental monitoring were between 2 to 3.5 times more
      likely to report risk behaviors examined. The promotion of specific parenting
      practices such as parental monitoring may hold promise for reducing adolescent
      risk behaviors in El Salvador.

PMID- 17195878
TI  - Research update: neurogenesis in adult brain and neuropsychiatric disorders.
AB  - Until recently neurogenesis in mammals was considered to occur only during the
      embryonic and early post-natal periods and to have no significant role in the
      adult nervous system. However, it is now accepted that neurogenesis occurs in two
      brain regions in adult mammals, namely, the hippocampus and olfactory bulb. In
      both regions new neurons arise from a resident population of neural progenitor
      cells that are maintained throughout adult life. Hippocampal neurogenesis is
      required for some types of hippocampal-dependent learning. Many factors enhance
      hippocampal neurogenesis including hormones, growth factors, drugs,
      neurotransmitters, and physical exercise as well as learning a hippocampal
      dependent task. Other factors suppress hippocampal neurogenesis; these include
      aging, stress, glucocorticoids and stimuli that activate the pituitary/adrenal
      axis. Recently much attention has become focused on the relevance of hippocampal
      neurogenesis to the pathophysiology and treatment of mood disorders. Indeed all
      major pharmacological and non-pharmacological treatments for depression enhance
      hippocampal neurogenesis and suppressing hippocampal neurogenesis in mice blocks
      behavioral responses in some antidepressant-sensitive tests. Altered hippocampal
      neurogenesis may also play a pathophysiological role in neurodegenerative
      disorders such as Alzheimer's disease. How much neurogenesis occurs normally in
      other brain regions is unclear. Neural progenitors are found throughout the
      neuraxis including both neurogenic and non-neurogenic regions. When cultured in
      vitro or isolated and transplanted back into neurogenic brain regions, these
      cells can differentiate into neurons although in their in situ location they seem
      to behave as lineage-restricted glial progenitors. The environmental cues that
      limit the potential of progenitor cells in non-neurogenic brain regions are
      unknown. However, an emerging view is that astrocytes, a subset of which also
      functions as neural progenitor cells, are critical in regulating the local
      environment. After transplantation into adult brain, neural stem cells are
      capable of surviving and differentiating into both neurons and glial cells,
      offering hope that stem cell therapy may be utilized to treat a variety of
      neurological and perhaps psychiatric disorders. The widespread existence of
      endogenous neural progenitors even in non-neurogenic brain regions also offers
      hope that the potential of these cells may be harnessed to repair cellular
      injuries caused by injuries such as stroke, trauma or neurodegenerative diseases.
      While obstacles remain to both approaches, stem-cell-based therapies remain an
      area of intense research interest.

PMID- 17195879
TI  - Neurobiology of anxiety disorders and implications for treatment.
AB  - The neurobiology of the anxiety disorders, which include panic disorder, post
      traumatic stress disorder (PTSD), and specific phobias, among others, has been
      clarified by advances in the field of classical or Pavlovian conditioning, and in
      our understanding of basic mechanisms of memory and learning. Fear conditioning
      occurs when a neutral conditioned stimulus (such as a tone) is paired with an
      aversive, or unconditioned stimulus (such as a footshock), and then in the
      absence of the unconditioned stimulus, causes a conditioned fear response.
      Preclinical studies have shown that the amygdala plays a key role in fear
      circuitry, and that abnormalities in amygdala pathways can affect the acquisition
      and expression of fear conditioning. Drugs such as glutamate N-methyl-D-aspartate
      (NMDA) antagonists, and blockers of voltage-gated calcium channels, in the
      amygdala, may block these effects. There is also preliminary evidence for the use
      of centrally acting beta-adrenergic antagonists, like propranolol, to inhibit
      consolidation of traumatic memories in PTSD. Finally, fear extinction, which
      entails new learning of fear inhibition, is central to the mechanism of effective
      anti-anxiety treatments. Several pharmacological manipulations, such as D
      cycloserine, a partial NMDA agonist, have been found to facilitate extinction.
      Combining these medication approaches with psychotherapies that promote
      extinction, such as cognitive behavioral therapy (CBT), may offer patients with
      anxiety disorders a rapid and robust treatment with good durability of effect.

PMID- 17195881
TI  - Psychiatric manifestations of nonconvulsive status epilepticus.
AB  - Nonconvulsive status epilepticus (NCSE) is clinically characterized by altered
      mental status and the diagnosis is confirmed by electroencephalography. Absence
      status (AS) and complex partial status (CPS) are the two primary types of NCSE.
      Patients in NCSE may exhibit a wide range of clinical presentations including
      subtle memory deficits, bizarre behavior, psychosis, or coma. While prognosis is
      dependent on the underlying etiology and possibly related to duration of the
      event, there is limited research in this area. Treatment focuses on correcting
      underlying pathologic abnormalities such as hyponatremia or drug toxicity, and
      initiating pharmacologic therapy. The benzodiazepines are considered the first
      line treatment for both AS and CPS.

PMID- 17195880
TI  - Developmental endocrine influences on gender identity: implications for
      management of disorders of sex development.
AB  - When a baby is born, the first medical pronouncement is usually, "It's a boy," or
      "It's a girl." In most cases, this pronouncement is based simply upon the
      appearance of the child's external genitalia. Due to variations in the process of
      sexual differentiation, sometimes the gender that should be assigned is not
      apparent from inspection of the external genitalia, either because they are
      "ambiguous" or because their appearance is not congruent with the internal
      anatomy. Decisions must be made not only about the most appropriate gender to
      assign the infant but also about the medical and rearing practices that will
      facilitate optimal psychological development and quality of life for the affected
      individual. This article will review the approach to managing gender disorders
      that has evolved since the 1950s. Three issues are identified as central to
      current shifts that are occurring in the management of these disorders: (a)
      increased understanding of the biological substrates of gender identity; (b)
      questions regarding the indications for irreversible cosmetic genital surgeries
      as a means of reinforcing gender assignments in infancy, and (c) ethical issues
      pertaining to informed consent and who is entitled to give it, particularly with
      regard to surgical gender reassignments in infancy. In keeping with the
      neuropsychiatry theme of this issue, the focus of this article is on prenatal
      sexual differentiation of the brain as it pertains to the question of
      psychosexual neutrality at birth.

PMID- 17195882
TI  - Women's cognitive and affective health and neuropsychiatry.
AB  - Recent interest in women's health has focused on the cognitive consequences of
      aging and hormonal changes. Based on hypotheses about estrogenic effects in the
      central nervous system (CNS), large-scale clinical trials were designed to
      address the efficacy of hormone replacement on protection against dementia and
      cognitive decline. Surprisingly, an absence of risk reduction for dementia and
      cognitive loss was found and much reanalysis of these findings has focused on
      timing of hormone replacement. Here we take a broad perspective to address a
      fuller range of psychological health. Gender differences in other psychiatric
      conditions including depression and anxiety have been attributed to hormones, and
      the neurotransmitter systems that are implicated in affective disorders may have
      an impact on cognitive impairment as well. Hormonal influences on neurotrophic
      mechanisms, as well as neurotransmitter effects, may be responsible for a breadth
      of neuropsychiatric conditions, particularly in aging. This review will focus on
      cognition, mood and anxiety issues among women with an emphasis on changes
      associated with aging. We will review data on the epidemiology of these entities
      and examine the biological mechanisms, which may be involved, with an emphasis on
      those mechanisms that may contribute to the multiple aspects of neuropsychiatry
      and women's health.

PMID- 17195883
TI  - The evaluation and management of the acutely agitated elderly patient.
AB  - Delirium is an organic mental syndrome defined by a global disturbance in
      consciousness and cognition, which develops abruptly and often fluctuates over
      the course of the day. It is precipitated by medical illness, substance
      intoxication/withdrawal or medication effect. Delirium is associated with
      significant morbidity and mortality, and is a leading presenting symptom of
      illness in the elderly. Elderly patients with altered mental status, including
      agitation, should be presumed to have delirium until proven otherwise. The
      clinical manifestations of delirium are highly variable. A mental status
      evaluation is crucial in the diagnosis of delirium. Medical evaluation and
      stabilization should occur in parallel. Life-threatening etiologies including
      hypoxia, hypoglycemia and hypotension require immediate intervention. The
      differential diagnosis of etiologies of delirium is extensive. Patients with
      delirium need thorough evaluations to determine the underlying causes of the
      delirium. Pharmacological agents should be considered when agitated patient has
      the potential to harm themselves or others, or is impeding medical evaluation and
      management. Unfortunately, the evidence to guide pharmacologic management of
      acute agitation in the elderly is limited. Current pharmacologic options include
      the typical and atypical antipsychotic agents and the benzodiazepines. These
      therapeutic options are reviewed in detail.

PMID- 17195884
TI  - Dementia: a brief review.
AB  - Dementia is an increasingly common diagnosis in our aging population, and the
      numbers are expected to rise exponentially in coming years. Alzheimer's disease
      alone now affects 4.5 million people in the US, while millions more are currently
      affected by vascular dementia, Lewy Body disease and frontotemporal dementia.
      Each of these is a distinct entity, though overlapping symptoms and comorbidities
      occur frequently. Within the past two decades research has progressed rapidly on
      multiple fronts, including epidemiology, etiology, pathology, diagnosis and
      treatment. It is important for clinicians to recognize early signs and symptoms
      of dementia, and to note critical differences among them. Dementia research has
      moved beyond description of symptoms and clinicopathological correlation to the
      elucidation of risk factors, the pathobiology of the disease process, and most
      important, to the first generation of dementia treatments. Our purpose here is to
      review the current state of knowledge and directions of research for the four
      major dementias noted above. We are entering an era of dementia care that will be
      based upon the identification of potentially modifiable risk factors and early
      disease markers, and the application of new disease-specific diagnostic tools and
      treatment modalities.

PMID- 17195885
TI  - Schizophrenia from a neuropsychiatric perspective.
AB  - Our understanding of schizophrenia has increased substantially in recent years.
      This is due to technological advances that have improved our ability to assess
      neuropsychiatric function and the genetic underpinnings of the disease. While
      diagnostic classification still relies on the presentation of the more overt
      symptoms of the disease, the neuropsychiatric perspective provides a more
      accurate and comprehensive understanding of the illness. This perspective
      provides insight into the etiology and treatment of schizophrenia. This article
      provides an overview of schizophrenia from the broad viewpoint of
      neuropsychiatry.

PMID- 17195886
TI  - Neurobehavioral consequences of traumatic brain injury.
AB  - At least 1.4 million people die, or receive hospital or emergency care every year
      in the United States as a result of traumatic brain injury (TBI). Many more are
      treated in other settings or receive no treatment at all. Thus TBI is often
      unidentified, with subsequent cognitive, behavioral, emotional and physical
      sequelae that are not linked to the injury. Yet, over 5.3 million Americans live
      with TBI-related disabilities that interfere with their overall performance and
      social roles within the community. The pathophysiology and consequences of TBI
      are discussed, as are functional changes and psychiatric manifestations after
      TBI. Finally, implications and recommendations for clinical practice are
      reviewed, including the importance of screening for TBI.

PMID- 17195888
TI  - Hyoid bone fractures.
AB  - Surgeons who manage patients with craniofacial trauma should be comfortable with
      evaluating and treating fractures throughout the head and neck. This includes the
      hyoid bone, which may cause significant airway concerns if fractured. The authors
      report the case of a patient who sustained a fracture of the hyoid bone. The
      hospital records from a busy, level I trauma center were reviewed to document
      similar injuries over a seven-year period. To supplement the scant literature
      concerning hyoid fractures, a review of the anatomy, diagnosis, and management of
      such injuries is provided.

PMID- 17195887
TI  - Neuropsychiatric disorders following vascular brain injury.
AB  - Several neuropsychiatric disorders such as mood, anxiety and psychotic disorders
      occur following cerebrovascular lesions. Post-stroke depression is the most
      common of these disorders and, along with post-stroke anxiety, has been shown to
      inhibit physical and cognitive recovery. Antidepressants have been shown to
      effectively treat post-stroke depression and to have a positive impact on
      rehabilitation efforts in patients suffering from this disorder. Much less is
      known about the potential impact of psychiatric conditions on recovery after
      stroke. Controlled trials will be able to adequately determine the effectiveness
      of treatment for these disorders.

PMID- 17195889
TI  - Laparoscopic enucleation of mesenteric cyst: a case report.
AB  - Intra-abdominal lesions, such as mesenteric cysts, are uncommon disorders. Most
      are discovered incidentally during routine abdominal examinations. They generally
      do not show typical clinical findings. Laparoscopic surgery has been used to
      remove a wide variety of mesenteric cysts. We report a patient with a mesenteric
      cyst, who was treated by laparoscopic enucleation.

PMID- 17195890
TI  - Propylthiouracil-related hemorrhagic diathesis: a case report and review of the
      literature.
AB  - We present an unusual case of a drug-related hemorrhagic diathesis. One month
      prior to admission, the patient was diagnosed at another medical center as having
      Graves' disease and propylthiouracil therapy (PTU) was initiated. Since clinical
      recovery was not achieved, the PTU was quickly increased to an unconventional
      daily dose of 1,000 mg. The patient was referred to our hospital because of
      spontaneous epistaxis, multiple ecchymoses and prolonged prothrombin time (PT)
      and activated partial thromboplastin time (aPTT), which developed soon after the
      increase in PTU dose. Drug-related hemorrhagic diathesis was considered, after
      other possible causes had been eliminated. To the best of our knowledge, this is
      the first reported case of spontaneous hemorrhage due to PTU use.

PMID- 17195891
TI  - Increased circulatory MMP-2 and MMP-9 levels and activities in patients with type
      1 diabetes mellitus.
AB  - BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder of unknown
      etiology. It has been suggested that metalloproteinases (MMPs) play important
      roles in the development and complications of autoimmune disorders. This article
      presents our research on the expression or activities of MMPs in Taiwanese T1DM
      patients. METHODS: Levels and activities of plasma MMP-2 and MMP-9 in patients
      with T1DM were investigated and compared to those of control individuals by
      enzyme-linked immunosorbent assay and zymography. RESULTS: Circulatory levels and
      activities of MMP-2 and MMP-9 in patients with T1DM were significantly higher
      than those in control subjects. CONCLUSIONS: MMP expression and activities are
      significantly increased in patients with T1DM. Our results not only document
      plasma MMPs levels and activities in the Taiwanese population (with a very low
      type 1 diabetic incidence), but also suggest that MMP expression and activity are
      elevated before the onset of complications in diabetic patients.

PMID- 17195892
TI  - Tuberculous meningitis presenting with unusually severe hyponatremia.
AB  - We report a patient with tuberculous meningitis who presented with unusually
      severe hyponatremia, an electrolyte disorder that may cause symptoms similar to
      those of tuberculous meningitis. The hyponatremia was probably due to the
      syndrome of inappropriate antidiuretic hormone secretion, and resolved after
      instituting water restriction and antituberculous medication.

PMID- 17195893
TI  - Orbital dystopia managed with unilateral brow suspension.
AB  - Patients with orbital dystopia present with symptoms of diplopia and/or facial
      asymmetry. Repositioning of the orbit requires multiple osteotomies around the
      orbit, which presents significant complications. The authors present an
      alternative method to restore facial symmetry in the case of a 14-year-old
      patient with congenital orbital dystopia due to fibrosis of the
      sternocleidomastoid muscle. The patient had no ocular symptoms but did have
      asymmetric descent of the ipsilateral brow. He refused box osteotomy and
      repositioning of the orbit. Unilateral brow suspension was performed using an
      endoscopic technique and suspension sutures fixed to resorbable screws. Adequate
      brow elevation was noted in the immediate postoperative period and at 6 months;
      it successfully restored facial symmetry.

PMID- 17195894
TI  - Pregnancy in the patient with Eisenmenger's syndrome.
AB  - Eisenmenger's syndrome occurs when a large congenital or surgically created shunt
      between the left and right sides of the heart causes an increase in pulmonary
      vascular resistance that equals or surpasses systemic resistance, resulting in a
      reversal of the shunt from a left-to-right shunt to a right-to-left or bi
      directional shunt. The maternal mortality rate of pregnancy in the presence of
      Eisenmenger's syndrome is reported to be as high as 50-65% with cesarean section.
      We present the case of a 32-year-old woman with Eisenmenger's syndrome who gave
      birth at 29 weeks of gestation via C-section to a healthy baby boy, and we review
      the literature regarding the management of such patients.

PMID- 17195895
TI  - HIV-related pulmonary hypertension.
AB  - With the availability of better treatment and prophylactic regimens for the
      infectious complications of human immunodeficiency virus (HIV), the non
      infectious complications are gaining greater attention. HIV-related pulmonary
      arterial hypertension (HIV-PAH) is one of these. The incidence of HIV-PAH is
      estimated at 0.5% of HIV-infected individuals. The pathogenesis remains unclear.
      Patients present with symptoms as diverse as progressive shortness of breath,
      pedal edema, dry cough, fatigue, syncope, as well as chest pain. Chest X-ray
      always shows cardiomegaly and prominent pulmonary artery, and evidence of right
      ventricular hypertrophy can be seen from the electrocardiogram. The pulmonary
      arterial systolic pressure, diastolic pressure and pulmonary vascular resistance
      from right heart catheterization are increased. There are a few small studies
      showing the benefit of prostacyclin analog (epoprostenol and iloprost) and
      bosentan. The role of antiretrovirals remains controversial, as do those of other
      agents such as calcium channel blockers and anticoagulants. The prognosis of HIV
      PAH is grave. Two thirds of HIV-PAH related mortality is usually secondary to
      consequences of pulmonary hypertension, with the worst survival noted in New York
      Heart Association (NYHA) functional class III-IV. The probability of survival in
      one series was 73%, 60% and 47% at one, two and three years, respectively.

PMID- 17195896
TI  - Splenic abscess in a patient with Wegener's granulomatosis treated with
      laparoscopic splenectomy.
AB  - Splenic abscess complicating Wegener's granulomatosis (WG) has not been
      previously described. We report the occurrence of a splenic abscess in a 45-year
      old white male suffering from WG. The patient presented with persistent fever and
      abdominal pain. Magnetic resonance imaging showed two splenic cystic lesions.
      Differential diagnosis was splenic hematoma or abscess. The patient underwent
      diagnostic laparoscopy and laparoscopic splenectomy. Pathology revealed a
      centrally located cavity full of pus and necrotic material. Although there were
      no signs of active vasculitis, all other histological features were compatible
      with WG. The patient had an uneventful postoperative course and his disease is in
      remission. Laparoscopic splenectomy appears to be a safe procedure, but its
      impact on the management of splenic abscess needs to be determined further.

PMID- 17195897
TI  - A case report of fatal oral ingestion of resorcinol.
AB  - Resorcinol is a pharmaceutical agent used topically in dermatological treatments
      for acne, eczema, psoriasis and related skin conditions. Although there are a few
      studies that indicate chronic toxic effects of resorcinol on humans after topical
      application, information on the effects of resorcinol in acute poisoning after
      oral ingestion is limited. Thus, we wish to report the clinical and laboratory
      findings of a patient who was admitted to our emergency department (ED) after
      inadvertent oral ingestion of resorcinol and later died, as well as the patient's
      autopsy findings. The major clinical and laboratory findings were
      unconsciousness, respiratory failure that required mechanical ventilation,
      generalized tonic-clonic seizures, leukocytosis and severe metabolic acidosis. In
      the blood sample taken at the autopsy, a high level of methemoglobin was found.
      In the serum, resorcinol was revealed by gas chromatography-mass spectrometry. It
      can be concluded that the basic approach to patients with resorcinol poisoning
      should include initial stabilization of the patient by supporting the airway,
      respiration and circulation, and treating complications such as seizures or
      metabolic acidosis in the ED, as soon as possible after oral ingestion.

PMID- 17195898
TI  - Managing the blue man: multiple traumas involving a paint-carrying truck.
AB  - INTRODUCTION: This report describes the difficulty in evaluating a patient with
      multiple traumas because he was covered with paint poured from a truck in a car
      accident. Cleansing with paint thinner and isotonic saline solution was
      necessary. CASE REPORT: A 29-year-old male patient was admitted to the emergency
      department following the collision of his car with a paint-carrying truck. His
      head, face, neck and hands were covered with a cyan-blue oil paint, and bloody
      "paint mud" covered all frontal and occipital areas of the scalp. Abdominal
      guarding was identified. A rapid cleansing with normal saline solution (0.9%
      NaCl) was attempted in order to expose the lesions of the patient, but it had no
      effect on the drying paint. The patient's scalp, face and neck were cleaned with
      paint thinner (60% toluene). The patient was then diagnosed as having a
      maxillofacial fracture and underwent surgery for open reduction and rigid
      fixation by plastic and reconstructive surgeons. Thinner was not used for the
      eyes for fear of further chemical injury. Normal saline removed corneal and
      conjunctival paint remnants but proved ineffective for cleansing of the eyelids
      and eyelashes. CONCLUSION: Removal of the paint from the skin and the eyes was a
      prerequisite for the evaluation of the underlying structures. It is difficult to
      find a cleansing material that can be used effectively and safely in different
      parts of the body.

PMID- 17195899
TI  - Parental lack of care and overprotection. Longitudinal associations with DSM-III
      R disorders.
AB  - BACKGROUND: This study served to replicate and extend the findings from the
      National Comorbidity Survey [Enns MW, Cox BJ, Clara I (2002) Psychol Med 32:997
      1008], in examining associations between recalled parental bonding and the
      prevalence and incidence of mental disorders in adulthood. METHODS: Data were
      used from 4,796 adults aged 18-64, who had participated in three waves (i.e.,
      1996, 1997, and 1999) of a large-scale Dutch epidemiological study. RESULTS:
      Parental lack of care and overprotection were significantly associated with both
      prevalence and incidence of DSM-III-R disorders. However, the impact of parental
      bonding was modest, explaining only 1-5% of the variance in the occurrence and
      onset of psychopathology. Chi-square tests demonstrated there were no differences
      between the impact of paternal and maternal rearing behaviors on mental
      disorders, or between lack of care and overprotection in the prediction of mental
      disorders. CONCLUSIONS: Overall, individuals' recollections of parental lack of
      care and overprotection appear to be non-specifically, modestly related to the
      prevalence and incidence of DSM-III-R disorders in adults from the general
      population. Future research may examine indirect or mediated links between
      parental bonding and (clinical diagnoses of) mental health problems.

PMID- 17195900
TI  - Increasing the number of gray shades in medical display systems--how much is
      enough?
AB  - Medical images produced by x-ray detectors, computed tomography (CT) scanners,
      and other modalities typically contain between 12-16 bits/pixel, which
      corresponds to 4,096-65,536 shades of gray. On the other hand, we see that these
      images are visualized by means of medical displays that have much lower available
      number of gray shades. For a long time medical LCDs only supported 8 bits or 256
      shades of gray per pixel. With the introduction of medical displays optimized for
      mammography, the available number of gray scales increased to 1,024. Recently,
      several manufacturers announced new display systems with higher bit depth.
      Because higher bit depth often directly results in higher display cost, it is a
      logical question to ask if this is required or even useful at all. This paper
      will give an answer by investigating several aspects such as limitations of the
      human visual system, digital imaging and communication in medicine grayscale
      standard display function calibration, and characteristics of medical LCDs.

PMID- 17195902
TI  - Serotonin and its role in colonic function and in gastrointestinal disorders.
AB  - Serotonin (5-HT) is most commonly thought of as a neurotransmitter in the central
      nervous system. However, the predominant site of serotonin synthesis, storage,
      and release is the enterochromaffin cells of the intestinal mucosa. Within the
      intestinal mucosa, serotonin released from EC cells activates neural reflexes
      associated with intestinal secretion, motility, and sensation. Two important
      receptors for serotonin that are located in the neural circuitry of the
      intestines are the 5-HT(3) and 5-HT(4) receptors; these are the targets of drugs
      designed to treat gastrointestinal disorders. 5-HT(3) receptor antagonists are
      used to treat nausea and emesis associated with chemotherapy and for functional
      disorders associated with diarrhea. 5-HT(4) receptor agonists are used as
      promotility agents to promote gastric emptying and to alleviate constipation.
      Because of the importance of serotonin in normal gut function and sensation, a
      number of studies have investigated potential changes in mucosal serotonin
      signaling in pathologic conditions. Despite the inconsistencies in the current
      literature, changes in serotonin signaling have now been demonstrated in
      inflammatory bowel disease, irritable bowel syndrome, postinfectious irritable
      bowel syndrome, and idiopathic constipation. Emerging evidence has led to many
      contradictory theories regarding serotonin signaling and its roles in the
      pathology of gut disorders. This review summarizes the current medications
      affecting serotonin signaling and provides an overview of our current knowledge
      of the changes in serotonin that occur in pathologic conditions.

PMID- 17195901
TI  - Vascular endothelial growth factor and cyclooxygenase-2 are overexpressed in
      ileal pouch-anal anastomosis.
AB  - PURPOSE: Pathophysiology of pouchitis after ileal pouch-anal anastomosis is
      controversial because of the potential for development of carcinoma.
      Cyclooxygenase-2-derived prostaglandins may be involved in the inflammatory
      process and play a role in the pathogenesis of colon cancer. Vascular endothelial
      growth factor plays a major role in neoangiogenesis and is overexpressed in a
      number of gastrointestinal malignancies. The goal of this study was to evaluate
      the expression of cyclooxygenase-2 and vascular endothelial growth factor and to
      assess neoangiogenesis and epithelial cell proliferation in patients with ileal
      pouch-anal anastomosis. METHODS: Endoscopic biopsies were obtained from 15
      patients with ileal pouch-anal anastomosis without pouchitis (10 biopsies from
      the ileal pouch and 10 from ileal nonpouch mucosa) and from 15 subjects with
      irritable bowel syndrome (10 biopsies from normal-appearing ileum and rectum).
      Cyclooxygenase-1, cyclooxygenase-2, and vascular endothelial growth factor
      messenger ribonucleic acid expression was determined by reverse transcriptase
      polymerase chain reaction. Cyclooxygenase-2 and vascular endothelial growth
      factor protein expression was evaluated by Western blot. Cyclooxygenase-2,
      vascular endothelial growth factor, CD34 (neoangiogenesis marker), and Ki67
      (proliferation marker) mucosal localizations were evaluated by
      immunohistochemistry. RESULTS: Expression of cyclooxygenase-2 and vascular
      endothelial growth factor was increased in ileal pouch mucosa compared with ileal
      nonpouch mucosa, normal ileum, and rectum. Cyclooxygenase-2 and vascular
      endothelial growth factor immunostaining in ileal pouch mucosa was more intense
      in the crypt area than in the surface epithelium compared with ileal nonpouch
      mucosa. CD34 (neoangiogenesis marker) and Ki67 (proliferation marker) expression
      was increased in ileal pouch mucosa. CONCLUSIONS: Cyclooxygenase-2 and vascular
      endothelial growth factor are overexpressed in the ileal pouch mucosa. This is
      associated with increased proliferative activity and neoangiogenesis.
      Cyclooxygenase-2 and vascular endothelial growth factor overexpression might play
      a role in the pathogenesis of pouchitis.

PMID- 17195903
TI  - Comparison between local ablative therapy and chemotherapy for non-resectable
      colorectal liver metastases: a prospective study.
AB  - BACKGROUND: There is a growing interest for the use of local ablative techniques
      in patients with non-resectable colorectal liver metastases. Evidence on the
      efficacy over systemic chemotherapy is, however, extremely weak. In this
      prospective study we aim to assess the additional benefits of local tumour
      ablation. METHODS: A consecutive series of 201 colorectal cancer patients,
      without extrahepatic disease, that underwent laparotomy for surgical treatment of
      liver metastases, were prospectively followed for survival and HRQoL. At
      laparotomy three groups were identified: patients in whom radical resection of
      metastases proved feasible, patients in whom resection was not feasible and
      received local ablative therapy, and patients in whom resection or local ablation
      was not feasible for technical reasons and who received systemic chemotherapy.
      FINDINGS: Patients in the chemotherapy and in local ablation group were
      comparable for all prognostic variables tested. For the local ablation group
      overall survival at 2 and 5 years was 56 and 27%, respectively (median 31 months,
      n = 45), for the chemotherapy group 51 and 15%, respectively (median 26 months, n
      = 39) (P = 0.252). After resection these figures were 83 and 51%, respectively
      (median 61 months, n = 117) (P < 0.001). The median DFS after local ablation was
      9 months, HRQoL was restored within 3 months. Patients after local ablation
      gained far more QALY's (317) than in the chemotherapy group (165) (P < 0.001).
      INTERPRETATION: Although overall survival did not reached statistical
      significance, the median DFS of 9 months suggests a beneficial effect of local
      tumour ablation for non-resectable colorectal liver metastases. Moreover,
      compared with systemic chemotherapy more QALY's were gained after local ablative
      therapy.

PMID- 17195904
TI  - Clinical characteristics and surgical outcome in hepatocellular carcinoma without
      hepatitis B virus surface antigen or hepatitis C virus antibody.
AB  - OBJECTIVE: We investigated clinical characteristics and surgical outcome of
      hepatocellular carcinoma in association with hepatitis viral status. No consensus
      exists concerning differences in surgical outcome in patients with hepatocellular
      carcinoma according to viral hepatitis status, especially those negative for
      hepatitis B virus surface antigen and antibody to hepatitis C virus. METHODS:
      Clinicopathologic data were available for 39 hepatectomy patients with
      hepatocellular carcinoma who were negative for hepatitis B virus surface antigen
      and hepatitis C virus antibody. Clinical characteristics and surgical outcome
      were analyzed retrospectively and compared to those patients with positive
      hepatitis viral markers. RESULTS: Patients negative for viral hepatitis markers
      were more likely to have large, advanced-stages tumors with relatively well
      preserved liver function and had a lower incidence of intrahepatic recurrences (P
      = 0.009). The intrahepatic recurrence rate reached a plateau at approximately 3
      years after resection in patients with negative viral markers, while it continued
      to increase steadily in patients positive for viral hepatitis markers. By
      multivariable analysis, the absence of viral hepatitis markers predicted a
      decreased rate of intrahepatic recurrence (relative risk, 0.222; P = 0.001).
      CONCLUSIONS: Adequate surgical resection in hepatocellular carcinoma patients
      negative for viral markers offers a good survival benefit, regardless of the
      etiology of the hepatocellular carcinoma.

PMID- 17195905
TI  - Kinase mutations and imatinib mesylate response for 64 Taiwanese with advanced
      GIST: preliminary experience from Chang Gung Memorial Hospital.
AB  - PURPOSE: Most gastrointestinal stromal tumors (GISTs) express constitutively
      activated mutation of kit or platelet-derived growth factor receptor alpha
      (PDGFRA), which are therapeutic targets for imatinib. Results of 64 Taiwanese
      with advanced GIST treated with imatinib were reported. METHOD AND MATERIALS:
      Between 2001 and May 2006, a prospective, non-randomized, and a single center
      trial containing 64 Taiwanese patients with advanced GIST treated with imatinib
      was conducted. Each tumor was investigated for mutations of kit or PDGFRA.
      RESULTS: The median follow-up time after imatinib administration was 16.1 months.
      12 patients (18.8%) had complete response (CR), 24 (37.5%) had a partial response
      (PR), 12 stationary disease (18.8%), 16 progressive disease (25.0%). The 64
      Taiwanese with advanced GIST had an estimated median survival of 48.0 months and
      4-year survival rate for 76.1%. Kit mutation was found in 49 of 54 (90.7%) test
      patients and five of them had no mutation (9.3%). No PDGFRA mutant was
      identified. In 40 patients harboring kit exon 11 mutations, the CR and PR rates
      (ORR) were 57.5% , nine patients with tumors containing kit exon 9 mutation had
      ORR rates of 22.2%, and five patients with no mutation had ORR rates of 60.0%
      (not significant; P = 0.149). CONCLUSIONS: Activated mutation of kit constituted
      90.7% genetic alteration of Taiwanese with advanced GIST and no PDGFRA mutation
      was detected. Imatinib induced a sustained objective response in more than half
      of Taiwan advanced GIST patients. ORR did not differ between patients whose GISTs
      had no mutation, kit exon 9, and 11 mutations.

PMID- 17195906
TI  - Effect of combined therapy with low-dose 5-aza-2'-deoxycytidine and irinotecan on
      colon cancer cell line HCT-15.
AB  - BACKGROUND: Aberrant promoter hypermethylation is an epigenetic change that
      silences the expression of crucial genes, resulting in inactivation of the
      apoptotic pathway in various cancers. This hypermethylation can be restored by
      the demethylating agent 5-aza-2'-deoxycytidine (DAC). DAC might increase the
      tumor sensitivity to chemotherapy through demethylation and restoration of gene
      expression. We investigated the effect of combined therapy with DAC and
      irinotecan (CPT-11) on the human colon cancer cell line HCT-15. METHODS: Human
      colon cancer cell line HCT-15 was treated with DAC and/or CPT-11 both in vitro
      and in vivo. The changes in mRNA expression of several apoptosis-related genes
      were investigated by reverse transcriptase-polymerase chain reaction (PCR).
      Promoter methylation was detected by methylation-specific PCR and combined
      bisulfite restriction analysis. Suppression of tumor growth was observed during
      the treatment with DAC and/or CPT-11 and apoptosis in the tumors was investigated
      by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assay.
      RESULTS: Promoter methylation of p14ARF, p16 INK4a, BNIP3, and XAF1 was
      confirmed, and DAC restored mRNA expression of these genes. Demethylation and
      restoration of gene expression was observed with low-dose DAC, and demethylation
      status was sustained for several weeks. Combined therapy with DAC and CPT-11
      produced marked suppression in tumor growth compared with DAC or CPT-11 alone,
      both in vitro and in vivo. CONCLUSIONS: Pretreatment with low-dose DAC may have
      the potential to be used as a "biosensitizer" of DNA-damaging agents such as CPT
      11 when the apoptotic pathway is inactivated as a result of aberrant promoter
      methylation in the cancer.

PMID- 17195907
TI  - Receptor activator of nuclear factor-kappaB ligand (RANKL) expression in
      hepatocellular carcinoma with bone metastasis.
AB  - BACKGROUND: Although receptor activator of nuclear factor-kappaB ligand (RANKL)
      seems to be involved in the development of bone metastases in several malignant
      tumors, its role in hepatocellular carcinoma (HCC) has not been investigated.
      METHODS: We retrospectively examined the immunohistochemical expression of RANKL
      in formalin-fixed, paraffin-embedded resected specimens obtained from 96 patients
      with HCC with (n = 16) and without (n = 80) bone metastases. In addition, tumor
      RANKL mRNA expression was evaluated by reverse transcriptase-polymerase chain
      reaction (RT-PCR) in five selected patients. We analyzed the relationship between
      RANKL expression level, bone metastasis development, and survival rate of
      patients with HCC after hepatic resection. RESULTS: Of the 96 patients with HCC,
      serum hepatitis C virus antibody was detected in 43.5% of patients and hepatitis
      B surface antigen in 29.5% of patients. Thirty-three patients (36.5%) also had
      liver cirrhosis. Immunohistochemical analysis showed that RANKL protein was
      present in 10 (62.5%) of 16 patients with HCC with bone metastasis compared with
      21 (26.3%) of 80 patients with HCC without bone metastasis; we found that RANKL
      expression was statistically significantly correlated to bone metastasis
      development (P < .01). RANKL mRNA expression was confirmed by RT-PCR in patients
      positive for RANKL protein expression by immunohistochemistry. The 5-year cancer
      related (P < .01) and disease-free survival (P < .01) rates after hepatic
      resection were statistically significantly worse in patients positive for RANKL
      expression compared with RANKL-negative patients. CONCLUSIONS: Some HCC cells
      produced the crucial bone resorption regulator RANKL. Because RANKL modulates
      bone turnover, its presence would have profound implications for the
      establishment and development of bone metastases.

PMID- 17195908
TI  - STAT1 activation-induced apoptosis of esophageal squamous cell carcinoma cells in
      vivo.
AB  - BACKGROUND: The induction of apoptosis might be a promising treatment for cancers
      refractory to conventional therapies, such as esophageal cancer. In this study,
      we examined whether epidermal growth factor-induced growth inhibition results
      from apoptosis of esophageal squamous cell carcinoma (SCC) cells as a result of
      STAT1 activation and evaluated whether interferon gamma (IFN-gamma) can induce
      apoptosis of cancer cells in vivo. METHODS: To assess the function of STAT1, we
      established stable transfectants expressing dominant-negative STAT1. Apoptosis
      was assessed by several experimental techniques, including flow cytometry.
      Differentiation was evaluated by Western blot test with involucrin used as a
      marker. In vivo, cancer cells were injected into male BALB/c nu/nu mice. Two
      weeks later, the mice started to receive injections of IFN-gamma or saline into a
      tail vein four times per week. Concentrations of IFN-gamma in the tumors were
      analyzed by enzyme-linked immunosorbent assay. Apoptosis was evaluated by TUNEL
      (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining. RESULTS:
      Epidermal growth factor inhibited the growth of esophageal SCC cells by causing
      apoptosis through several pathways involving STAT1 activation. IFN-gamma induced
      the apoptosis of cancer cells, but it also promoted the differentiation (not
      apoptosis) of primary cultured cells derived from normal esophageal epithelium.
      IFN-gamma also inhibited the growth of xenograft tumors of esophageal SCC cells
      in vivo. CONCLUSIONS: Our results suggest that IFN-gamma is one candidate for
      cytokine-based therapy of cancer. IFN-gamma-induced STAT1 activation might be
      involved in the apoptosis of esophageal SCC cells and in the terminal
      differentiation of normal squamous cells. Further studies of STAT1 signaling
      pathways may provide the basis for new targeted therapeutic strategies for
      esophageal SCC.

PMID- 17195909
TI  - Secondary cytoreductive surgery in patients with platinum-sensitive recurrent
      ovarian cancer.
AB  - BACKGROUND: Secondary surgical cytoreduction (SCR) represents a promising
      therapeutic strategy for patients affected by ovarian cancer disease recurrence.
      The aim of this prospective observational trial was to analyze the role of SCR in
      patients with platinum-sensitive ovarian cancer. METHODS: Patients with platinum
      sensitive ovarian cancer underwent SCR by a single surgical team. Clinical and
      oncologic data were prospectively recorded. A total of 47 patients underwent SCR
      from 1999 to 2003. RESULTS: The mean operating time was 210 minutes, and mean
      blood loss was 500 mL. The most frequent surgical procedures carried out were
      splenectomy, lymphadenectomy, bowel resection, and extensive peritonectomy.
      Optimal cytoreduction was achieved in 41 patients. Thirty-seven patients had no
      visible tumor at the end of SCR. Overall median survival was 49 months. Patients
      who achieved optimal residual disease had a median survival of 61 months, whereas
      patients who had residual disease >1 cm had a median survival of 19 months.
      CONCLUSIONS: Positive CA-125 (cancer antigen 125) was identified as a negative
      prognostic factor at multivariate analysis. After careful selection, optimal
      cytoreduction can be achieved in most patients who are subjected to SCR with
      acceptable morbidity. Residual tumor and CA-125 represent the most important
      prognostic factors.

PMID- 17195910
TI  - The utility of intraoperative evaluation of sentinel lymph nodes in breast
      cancer.
AB  - BACKGROUND: In breast cancer treatment, intraoperative sentinel lymph node (SLN)
      evaluation is used to identify patients who may potentially benefit from
      immediate completion of axillary lymph node dissection. METHODS: Prospectively
      collected breast cancer registry data identified 516 SLN biopsies between January
      2003 and December 2005. Intraoperative evaluation (IE) of the SLNs was performed
      in 479 axillae. Final pathology by hematoxylin and eosin and, for negative nodes,
      by immunohistochemical stains was compared with the IE result. The effect of IE
      and final pathology on surgical treatment was examined. RESULTS: The
      sensitivities for IE of N0(i+) (n = 39), N1mi (n = 41), and N1a-3a (n = 89)
      metastases were 0%, 5%, and 63%, respectively. The specificity was 99.7%. IE
      identified 57 (44%) of SLN-positive (N1mi and N1a-3a) axillae, thus resulting in
      synchronous axillary lymph node dissection for those patients. Reoperation for
      false-negative IEs (N1mi or N1a-3a with negative IE) occurred in only 27 axillae
      (39%). CONCLUSIONS: IE of SLNs has adequate sensitivity and excellent
      specificity. In addition to allowing patients to benefit from synchronous
      surgery, IE helped patients to receive care in concordance with recommended
      practice guidelines. The false-negative IE of SLNs highlights uncertainty with
      the clinical significance of axillary nodal staging when only small amounts of
      metastatic disease are identified in the axilla.

PMID- 17195911
TI  - Down-regulation of pro-apoptotic genes is an early event in the progression of
      malignant melanoma.
AB  - INTRODUCTION: Down-regulation of apoptosis genes has been implicated in the
      development and progression of malignant melanoma. We used cDNA microarray to
      evaluate pro-apoptotic gene expression comparing normal skin to melanoma (thin
      and thick), nodal disease and distant metastases. METHODS: Twenty-eight specimens
      including skin (n = 1), thin melanoma (n = 6), thick melanoma (n = 7), nodal
      disease (n = 6), and distant metastases (n = 8), were harvested at the time of
      resection from 16 individuals. RNA was isolated and microarray analysis utilizing
      the Affymetrix GeneChip (54,000 genetic elements, U133A+B... levels) was
      performed. Mean level of expression was calculated for each gene within a sample
      group. Expression profiles were then compared between tissue groups. Student's t
      test was used to determine variance in expression between groups. RESULTS: We
      reviewed the expression of 54,000 genetic elements, of which 2,015 were found to
      have significantly altered expression. This represents 1,602 genes. Twenty-two
      pro-apoptotic genes were found to be down-regulated when compared to normal skin.
      Overall reduction was evaluated comparing normal skin to metastases with a range
      of 3.31-64.04-fold-decrease. When comparing the tissue types sequentially, the
      greatest fold-decrease in gene expression occurred when comparing skin to all
      melanomas (thin and thick) (p = 0.011). Subset analysis comparing normal skin to
      thin melanoma or thick melanoma, revealed the greatest component of overall
      reduction at the transition from thin to thick lesions (p = 0.003). CONCLUSION:
      Sequential down-regulation of pro-apoptotic genes is associated with the
      progression of malignant melanoma. The greatest fold-decrease occurs in the
      transformation from thin to thick lesions.

PMID- 17195912
TI  - Role of the BRAF mutations in the microsatellite instability genetic pathway in
      sporadic colorectal cancer.
AB  - BACKGROUND AND AIMS: Between 10 and 15% of all cases of colorectal cancer are the
      result of microsatellite instability (MSI) in the genetic pathway due to an
      alteration in the DNA repair genes. Tumors with high MSI are characterized by a
      better prognosis. The BRAF oncogene has been linked to the MSI pathway in
      tumorogenesis. The objective of this study was to determine whether alterations
      in BRAF are related to MSI and whether they can result in differences in survival
      rates. METHODS: The study cohort comprised 351 patients diagnosed with sporadic
      colorectal cancer. MSI was determined in accordance with the National Cancer
      Institute's (NCI) recommendations by means of PCR and sequence analyses.
      Mutational analysis of the BRAF gene was performed by real-time PCR and
      subsequent sequencing of the altered samples. The methylation pattern of the
      hMLH1 gene was determined using methylation-specific PCR analyses of bisulfite
      treated DNA and the results confirmed by sequencing. RESULTS: Of the patients
      tested, 6.9% showed high MSI and 3.7% showed a BRAF gene mutation. hMLH1
      methylation was observed in 67.2% of the patients with MSI and/or the BRAF
      alteration. The BRAF mutation was related to the MSI genetic pathway (P < 0.0001)
      and with hMLH1 methylation. In the analysis of overall survival only MSI had an
      independent prognostic value for the risk of death. Patients with the BRAF
      mutation showed a higher risk of death, although this association was found not
      to be statistically significant. CONCLUSIONS: There is a subgroup of carcinomas
      which develop via the MSI pathway that carry an alteration of the BRAF gene. This
      alteration confers a poorer outcome on these patients within the total group of
      patients with MSI who have a better prognosis. This hypothesis should be further
      investigated in a larger study population due to the low incidence of BRAF
      mutations in colorectal cancer.

PMID- 17195913
TI  - Outcome after hepatectomy for multiple (four or more) colorectal metastases in
      the era of effective chemotherapy.
AB  - BACKGROUND: Hepatic resection is generally accepted as the only potential for
      long-term survival in patients with colorectal metastases confined to the liver.
      Despite an unknown benefit, hepatic resection is playing an increasing role in
      patients with extensive disease. METHODS: A retrospective review of a
      prospectively maintained hepatobiliary surgical database was carried out. Outcome
      after hepatectomy for four or more colorectal hepatic metastases was reviewed.
      RESULTS: Between 1998 and 2002, out of a total of 584 patients, 98 (17%) with
      four or more colorectal hepatic metastases were resected. Actuarial 5-year
      survival was 33% for the entire group, with seven actual 5-year survivors. There
      were no perioperative deaths, and the perioperative morbidity was 28%. Positive
      margins and extrahepatic disease resection were independently associated with
      poor outcome. The median disease-free survival was 12 months, with no actuarial
      disease-free survivors at 5 years. Recurrence pattern, response to neoadjuvant
      chemotherapy, time to recurrence, and resection of recurrent disease were also
      associated with outcome. CONCLUSIONS: Long-term survival can be achieved after
      resection of multiple colorectal metastases; however, because most patients will
      experience recurrence of disease, effective adjuvant therapy and close follow-up
      is necessary.

PMID- 17195914
TI  - The role of sentinel lymph node biopsy in Paget's disease of the breast.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy has become a standard of care for
      axillary lymph node staging in breast cancer and appears suitable for virtually
      all patients with clinically node-negative (cN0) invasive disease. However, its
      role in Paget's disease of the breast, a condition in which invasion may or may
      not be present, remains undefined. METHODS: Among 7,083 consecutive SLN biopsy
      procedures, we retrospectively identified 39 patients with Paget's disease of the
      breast. Nineteen patients had no associated clinical/radiographic features
      ("Paget's only"), and 20 patients had associated clinical/radiographic findings
      ("Paget's with findings"). RESULTS: The mean ages for the Paget's alone and with
      findings groups were 63.6 and 49.6 years, respectively. The use of breast
      conservation therapy was 32% in the Paget's alone group and 10% in the Paget's
      with findings group. Invasive carcinoma was found in 27% of patients in the
      Paget's alone group and 55% of patients in the Paget's with findings group. The
      success rate of SLN biopsy was 98%, and the mean number of SLNs removed was 3 in
      both groups. In the entire cohort of Paget's disease, 28% (11/39) of the patients
      had positive SLNs (11%, Paget's alone; 45%, Paget's with findings). CONCLUSION:
      In our "Paget's only" cohort, invasive cancer was found in 27% of cases and
      positive SLNs in 11%. SLN biopsy should be considered in all patients with
      Paget's disease of the breast, whether associated clinical/radiographic findings
      are present.

PMID- 17195916
TI  - How to bridge the gap between available information and clinical concepts and
      practice?

PMID- 17195915
TI  - Predictive power of biomarkers of oxidative stress and inflammation in patients
      with hepatitis C virus-associated hepatocellular carcinoma.
AB  - BACKGROUND: This study evaluated the relationship between inflammation, intra
      hepatic oxidative stress, oxidative DNA damage and the progression of liver
      carcinogenesis in hepatitis C virus (HCV)-infected humans. METHODS: Non-cancerous
      liver tissues were collected from 30 patients with an HCV-associated solitary
      hepatocellular carcinoma (HCC) who received curative tumor removal. After
      surgery, the patients were followed at monthly intervals at the outpatient
      clinic. Distribution of the inflammatory cells (CD68+), the number of 8
      hydroxydeoxyguanosine (8-OHdG) DNA adducts and 4-hydroxynonenal (HNE) protein
      adducts and the expression of apurinic/apyrimidinic endonuclease (APE) were
      determined by immunohistochemical analysis in serial liver sections from tumor
      free parenchyma at the surgical margin around the tumor. RESULTS: Significant
      positive correlations were observed between the number of CD68+ cells, the amount
      of HNE protein adducts, and the number of 8-OHdG adducts in liver tissue of
      patients with HCC and HCV. The cumulative disease-free survival was significantly
      shorter in patients with the highest percentage of 8-OHdG-positive hepatocytes.
      Using a Cox proportional hazard model, 8-OHdG, HNE and CD68 were determined to be
      good biomarkers for predicting disease-free survival in patients with HCC and
      HCV. CONCLUSIONS: These results support the hypothesis that HCV-induced
      inflammation causes oxidative DNA damage and promotes hepatocarcinogenesis which
      directly affects the clinical outcome. Since patients with greater intra-hepatic
      oxidative stress had a higher incidence of HCC recurrence, we suggest that
      oxidative stress biomarkers could potentially be used as a useful clinical
      diagnostic tool to predict the duration of disease-free survival in patients with
      HCV-associated HCC.

PMID- 17195917
TI  - Orthostatic hypotension and attention in Parkinson's disease with and without
      dementia.
AB  - To compare frequency and degree of orthostatic hypotension (OH) in Parkinson's
      disease (PD) and Parkinson's disease with dementia (PDD) and its effect on
      attention and word fluency, blood pressure (BP) and heart rate changes during
      tilt were determined in 10 PD and 8 PDD patients. Attention and word fluency were
      evaluated in supine and tilted position using standard neuropsychological tests.
      OH defined as systolic BP (SBP) drop of >/=20 mmHg and/or diastolic BP (DBP) drop
      of >/=10 mmHg was present in 5 PDD patients and in 2 PD patients. SBP drop was
      significantly greater in PDD than in PD patients (P < 0.05). Whereas word fluency
      was unaffected by tilt in both patient groups, attention as assessed with the
      Test of Everyday Attention (TEA) deteriorated significantly in the PDD group,
      correlating with blood pressure response (DeltaSBP and TEA-2, r = 0.828, P <
      0.05; DeltaDBP and TEA-2, r = 0.828, P < 0.05). We conclude that OH is frequent
      in PDD and should be addressed therapeutically since it may exacerbate
      attentional dysfunction.

PMID- 17195918
TI  - Alteration in the GABAergic network of the prefrontal cortex in a potential
      animal model of psychosis.
AB  - The GABAergic input on cortical pyramidal cells has an important influence on the
      firing activity of the cortex and thus in regulating the behavioural outcome. The
      aim of the current study was to investigate the long-term neuroplastic adaptation
      of the GABAergic innervation pattern after an early severe systemic impact.
      Therefore 40 Mongolian gerbils (Meriones unguiculatus) were either reared under
      impoverished (IR) or enriched rearing conditions (ER) and received a single early
      (+)-methamphetamine (MA) challenge (50 mg/kg i.p.) or saline on postnatal day 14.
      The density of perisomatic immunoreactive GABAergic terminals surrounding layers
      III and V pyramidal neurons was quantified as well as the overall GABAergic fibre
      density in layers I/II and V of the medial prefrontal cortex (mPFC) of young
      adult animals (90 days). We found that IR in combination with an early MA
      administration led to a significant decrease in GABAergic bouton densities while
      the overall GABAergic fibre density increased in all investigated layers. The
      results indicate a shift in inhibition from somatic to dendritic innervation of
      pyramidal neurons in this potential animal model of psychosis. We conclude that
      IR combined with early MA trigger changes in the postnatal maturation of the
      prefrontal cortical GABAergic triggers innervation, which may interfere with
      proper signal processing within the prefrontal neural network.

PMID- 17195919
TI  - Quantification of total mitochondrial DNA and mitochondrial common deletion in
      the frontal cortex of patients with schizophrenia and bipolar disorder.
AB  - Data published during the last decade are suggestive of a role for mitochondrial
      dysfunction in the pathogenesis of schizophrenia, bipolar disorder and other
      psychiatric diseases. In order to determine if the mitochondrial deficits
      reported in the literature are caused by abnormalities in the mitochondrial DNA
      of psychiatric patients, we quantified mitochondrial DNA (mtDNA) levels and the 5
      kb common mitochondrial deletion (CD) in postmortem frontal cortex tissue. The
      mitochondrial CD and mtDNA levels were measured in tissue obtained from the
      frontal cortex (Brodmann Area 46) of 144 individuals (45 patients with
      schizophrenia, 40 patients with bipolar disorder, 44 controls, and 15 patients
      with major depression). These variables were measured using newly developed SYBR
      green and TaqMan real time PCR assays. Both the TaqMan and the SYBR green assays
      gave similar results. There was no statistically significant difference for the
      quantity of the common mitochondrial deletion between controls and patients. We
      also did not detect a difference in the mtDNA levels amongst the diagnosis
      groups. There were statistically significant differences for the evaluated
      parameters for smokers, schizophrenic patients on antipsychotic drugs at time of
      death, and bipolar patients with antidepressant use and alcohol abuse. Based on
      this study and other reports, we conclude that neither the common mitochondrial
      deletion nor changes in mitochondrial DNA levels are likely to account for the
      mitochondrial changes associated with bipolar disorder or schizophrenia. The
      effect of premortem agonal factors and medication on mitochondrial dysfunction
      still needs further elucidation.

PMID- 17195920
TI  - Restricted and repetitive behaviors in young children with autism spectrum
      disorders.
AB  - Restricted and repetitive behaviors (RRBs) on the Autism Diagnostic Interview-
      Revised (ADI-R: Lord, Rutter, & Le Couteur (1994) were examined in 165 children
      with Autism Spectrum Disorders (ASD), 49 children with non-spectrum developmental
      disorders (DD), and 65 children with typical development (TD) at approximately 2
      years of age. A factor analysis found evidence for a repetitive sensorimotor
      (RSM) factor and an insistence on sameness (IS) factor. Behaviors that loaded on
      the RSM factor were prevalent in children with ASD and significantly more common
      and severe than in children with DD or TD. On average, children with ASD had more
      RSM behaviors. Behaviors that loaded on the IS factor were relatively uncommon
      and did not differ in prevalence or severity across groups.

PMID- 17195921
TI  - Parental recognition of developmental problems in toddlers with autism spectrum
      disorders.
AB  - Symptoms of Autism Spectrum Disorders (ASD) begin to manifest during the first 2
      years; there is limited evidence regarding type and timing of symptom onset. We
      examined factors related to parental age of recognition (AOR) of early
      abnormalities and the association between AOR and diagnosis and levels of
      functioning at 2 and 4 years in 75 toddlers with ASD. Results suggest significant
      differences between autism and PDD-NOS in the AOR and type of first concerns.
      Early social and motor delays as well as maternal age was associated with AOR.
      Later AOR was associated with poorer social-communicative and nonverbal cognitive
      functioning at 2 and 4. The findings are discussed in a context of identifying
      distinct developmental trajectories within the autism spectrum.

PMID- 17195922
TI  - Acute variceal bleed in a patient with idiopathic myelofibrosis successfully
      treated with endoscopic variceal band ligation.

PMID- 17195923
TI  - Tricyclic antidepressants for chronic vomiting in diabetic patients.
AB  - Chronic vomiting in diabetic patients often is unresponsive to prokinetic agents
      and poorly explained by delayed gastric emptying or neuropathy. This
      retrospective study examines clinical response to tricyclic antidepressants, a
      treatment of reported benefit in nondiabetic patients with unexplained vomiting
      syndromes. Outcomes were studied in 24 diabetic outpatients who had been treated
      with tricyclic antidepressants specifically for nausea and vomiting after an
      unsatisfactory response to prokinetic therapy. Symptom patterns and treatment
      response were determined from chart review and telephone interview. Ten patients
      (42%) had recurrent, stereotypical vomiting episodes with symptom-free intervals
      suggesting cyclic vomiting syndrome; 14 (58%) had persistent symptoms. By chart
      review, at least moderate symptom response to tricyclic antidepressant treatment
      (median dosage, 50 mg/day) occurred in 88% of subjects, with complete or nearly
      complete resolution of symptoms in one-third. At follow-up interview, 77% self
      reported at least moderate symptom improvement during therapy and 68% rated
      tricyclic antidepressants the most effective treatment received. Duration of
      diabetes, presence of neuropathy, and psychiatric status were not predictive of
      treatment outcome in multivariate analysis, but a cyclical symptom pattern
      attenuated antidepressant response (P< 0.05). In this retrospective review, the
      majority of diabetic patients with chronic vomiting and incomplete response to
      prokinetic therapy benefited from tricyclic antidepressants in low-dose, open
      label regimens and rated them the most effective treatment received. This
      therapeutic option should be further studied in diabetic patients considering the
      morbidity of chronic vomiting in this population.

PMID- 17195924
TI  - Reconstruction of the ancestral ferungulate karyotype by electronic chromosome
      painting (E-painting).
AB  - By comparing high-coverage and high-quality whole genome sequence assemblies it
      is now possible to reconstruct putative ancestral progenitor karyotypes, here
      called protokaryotypes. For this study we used the recently described electronic
      chromosome painting technique (E-painting) to reconstruct the karyotype of the 85
      million-year-old (MYA) ferungulate ancestor. This model is primarily based on dog
      (Canis familiaris) and cattle (Bos taurus) genome data and is highly consistent
      with comparative gene mapping and chromosome painting data. The protokaryotype
      bears 23 autosomal chromosome pairs and the sex chromosomes and preserves most of
      the chromosomal associations described previously for the boreo-eutherian
      protokaryotype. The model indicates that five interchromosomal rearrangements
      occurred during the transition from the boreo-eutherian to the ferungulate
      ancestor. From there on 66 further interchromosomal rearrangements took place in
      the lineage leading to cattle and 61 further interchromosomal rearrangements in
      the lineage to dog.

PMID- 17195926
TI  - Survey of feline giardiasis by ELISA test in Italy.

PMID- 17195925
TI  - Molecular organization of terminal repetitive DNA in Beta species.
AB  - We have isolated families of subtelomeric satellite DNA sequences from species of
      four sections of the genus Beta and from spinach, a related Chenopodiaceae.
      Twenty-five clones were sequenced and representative repeats of each family were
      characterized by Southern blotting and FISH. The families of ApaI restriction
      satellite repeats were designated pAv34, pAc34, the families of RsaI repeats
      pRp34, pRn34 and pRs34. The repeating units are 344-362 bp long and 45.7-98.8%
      homologous with a clear species-specific divergence. Each satellite monomer
      consists of two subrepeats SR1 and SR2 of 165-184 bp, respectively. The repeats
      of each subrepeat group are highly identical across species, but share only a
      homology of 40.8-54.8% with members of the other subrepeat group. Two
      evolutionary steps could be supposed in the phylogeny of the subtelomeric
      satellite family: the diversification of an ancestor satellite into groups
      representing SR1 and SR2 in the progenitor of Beta and Spinacea species, followed
      by the dimerization and diversification of the resulting 360 bp repeats into
      section-specific satellite DNA families during species radiation. The chromosomal
      localization of telomeric, subtelomeric and rDNA tandem repeats was investigated
      by multi-colour FISH. High-resolution analysis by fibre FISH revealed a unique
      physical organization of B. vulgaris chromosome ends with telomeric DNA and
      subtelomeric satellites extending over a maximum of 63 kb and 125 kb,
      respectively.

PMID- 17195927
TI  - Multivariate survival analysis of histological parameters and clinical
      presentation in canine cutaneous mast cell tumours.
AB  - The Patnaik histological grade is a good method for the prediction of long-term
      mast cell tumour behaviour but it is influenced by subjective inter-observer
      variations and intratumoral heterogeneity. The present study evaluated each of
      the histopathological parameters used to formulate Patnaik's grade in terms of
      prognosis and tested whether they have a different prognostic sensitivity,
      thereby disclosing which could be considered more useful in the prediction of
      tumour recurrence and patient survival. Clinical presentation (single or multiple
      tumours) was also considered as possible prognostic factor. The results
      demonstrated that individual histological criteria together with multiple
      presentation may be of value in predicting the outcome of mast cell tumours.
      Among these, invasiveness (beta1.85; standard error 1.15) and the number of
      mitotic figures (beta3.01; standard error 1.18) showed high prognostic
      significance (Cox proportional hazard regression for censored data; chi-squared =
      15.52, degree of freedom = 6, p = 0.016) and could serve as reliable prognostic
      indicators avoiding more subjective parameters such as cellular differentiation,
      nuclear morphology and tumoural pattern.

PMID- 17195928
TI  - Deduced amino acid sequences surrounding the fusion glycoprotein cleavage site
      and of the carboxyl-terminus of haemagglutinin-neuraminidase protein of the
      avirulent thermostable vaccine strain I-2 of Newcastle disease virus.
AB  - A single-tube RT-PCR technique generated a 387 bp or 300 bp cDNA amplicon
      covering the F(0) cleavage site or the carboxyl (C)-terminus of the HN gene,
      respectively, of Newcastle disease virus (NDV) strain I-2. Sequence analysis was
      used to deduce the amino acid sequences of the cleavage site of F protein and the
      C-terminus of HN protein, which were then compared with sequences for other NDV
      strains. The cleavage site of NDV strain I-2 had a sequence motif of (112)
      RKQGRLIG(119), consistent with an avirulent phenotype. Nucleotide sequencing and
      deduction of amino acids at the C-terminus of HN revealed that strain I-2 had a 7
      amino-acid extension (VEILKDGVREARSSR. This differs from the virulent viruses
      that caused outbreaks of Newcastle disease in Australia in the 1930s and 1990s,
      which have HN extensions of 0 and 9 amino acids, respectively. Amino acid
      sequence analyses of the F and HN genes of strain I-2 confirmed its avirulent
      nature and its Australian origin.

PMID- 17195929
TI  - Optimization of wheat co-transformation procedure with gene cassettes resulted in
      an improvement in transformation frequency.
AB  - Genetic manipulation using gene cassettes was applied to the elite wheat variety
      EM12 via particle bombardment, which allows an improvement in transformation
      frequency. We simultaneously transferred to wheat immature embryos with two non
      linked genes, gus and bar, on either separate gene cassettes or one plasmid. The
      linear gene cassettes were excised and purified by restriction digestion of the
      plasmid, and consisted of promoters, open reading frames and terminators. No
      difference was observed in GUS transient expression of between gene cassettes and
      single whole plasmid. However, the stable transformation frequency was
      significantly increased to 1.1% using gene cassettes, compared with 0.4% when
      using single plasmid. Procedures of the efficient co-transformation with gene
      cassettes were developed. Factors influencing on the transformation frequency
      were also studied in order to optimize the procedure. These were acceleration
      pressure, target distance, gold particle size, the quantity ratio of gene
      cassettes and the age of target explants. Based on the transient and stable
      expression of the gus gene cassettes, optimization of transformation parameters
      improved the reproducibility of transformation in the elite wheat variety.

PMID- 17195930
TI  - A new species of Prohatschekia Nunes-Ruivo, 1954 (Copepoda: Hatschekiidae)
      parasitic on Scorpaena elongata (Cadenat) off Algeria.
AB  - A new species of parasitic copepod, Prohatschekia mediterranea n. sp.
      (Siphonostomatoida: Hatschekiidae), is described from a scorpaenid fish,
      Scorpaena elongata, collected off Algeria. This is the seventh species of
      Prohatschekia Nunes-Ruivo, 1954 to be described and the first record of the genus
      from the Mediterranean Sea. The new species is most closely related to P.
      cremouxi Nunes-Ruivo, 1954, known from a congeneric host collected in Senegal. A
      key is provided to distinguish the new species from other members of the genus.

PMID- 17195932
TI  - An evaluation of accuracy and repeatability of a novel gait analysis device.
AB  - INTRODUCTION: Restoration of gait is a particularly important patient-based
      functional outcome following lower extremity trauma. A new portable device which
      measures gait parameters, the IDEEA, may be particularly useful in evaluating
      post-traumatic gait parameters in the office setting, but the accuracy and
      repeatability of this device relative to standard gait laboratory footswitches
      are unknown. MATERIAL AND METHODS: Twelve healthy subjects were tested
      simultaneously using the IDEEA device and standard gait laboratory footswitches,
      at slow, medium, and fast speeds. Parameters evaluated were single-limb support
      time (SLS), double-limb support time (DLS), swing phase duration (SPD), cycle
      duration, and cadence. RESULTS: The repeatability between right and left
      measurements tended to be better for the IDEEA, and was at least as good as the
      foot switches. The absolute differences of the timed gait parameters between the
      two devices were all in the range of 0.03 s, which is within the data sampling
      resolution of the gait laboratory foot switches (0.04 s). Furthermore, assuming a
      1-s gait cycle, these differences account for only 3% of the gait cycle, which is
      also well within the clinical parameters for evaluating and differentiating
      between treatments. CONCLUSION: This device is accurate and repeatable, and may
      facilitate the evaluation of gait function in post-traumatic patients in settings
      outside of the traditional gait laboratory.

PMID- 17195931
TI  - Hippocampal sclerosis dementia differs from hippocampal sclerosis in frontal lobe
      degeneration.
AB  - Hippocampal sclerosis (HS) is characterized by selective neuronal loss and
      gliosis in CA1 and the subiculum and has been associated with several disorders,
      including Alzheimer's disease, frontotemporal lobar degeneration with ubiquitin
      immunoreactive inclusions (FTLD-U), vascular dementia and some tauopathies. In
      some cases, HS is not associated with other degenerative pathologies. Such cases
      are sometimes referred to as HS dementia (HSD). Differences between HSD and HS in
      the setting of FTLD-U have not been systematically investigated. To this end,
      eight cases of HSD and ten cases of HS associated with FTLD-U were studied with
      Nissl and periodic acid-Schiff stains to assess neuronal loss and corpora
      amylacea, respectively. Sections were immunostained with antibodies to glial
      fibrillary acidic protein, HLA-DR and synaptophysin and immunoreactivity was
      measured with image analysis in CA1 and the subiculum of each case. Additionally,
      sections were immunostained with antibodies to 4-R tau to determine the presence
      of argyrophilic grains. HSD was different from HS associated with FTLD-U.
      Specifically, it was more common in the elderly, and it was associated with more
      marked neuronal and synaptic loss and with greater reactive gliosis. Corpora
      amylacea tended to be more frequent in HSD than in FTLD-U, but there was no
      difference in frequency of argyrophilic grains.

PMID- 17195933
TI  - Surgical outcomes after treatment of fractures in femur and tibia in
      pycnodysostosis.
AB  - Pycnodysostosis is a rare hereditary disease, characterized by systemic bone
      sclerosis. The most important orthopedic problem in this condition is the
      recurrent pathological fracture of long bones. In this paper, the surgical
      results for fractures of six limbs (three femurs and three tibias) in five cases
      of pycnodysostosis are reported. Five limbs achieved fracture union and union is
      developing in one tibia after intramedullary nail (IM) nailing or Ilizarov
      external fixation (IEF), although fracture line tends to persist for longer
      periods of time. One femoral fracture was treated by IM nailing, and one femoral
      and one tibial fracture were treated by IEF leading to final bone union. One
      femoral and one tibial fracture were initially treated by IEF, and were treated
      by IM nailing after re-fracture. One tibial fracture was initially treated by IEF
      leading to a failure of union, and was converted to IM nailing. All cases are
      able to walk; one case requires a single crutch. Infection was noted in two limbs
      after IM nailing following IEF. Fixation with IM nail was effective in preventing
      re-fracture as well as in alignment correction. Although the surgical technique
      is more difficult, IM nailing in the initial surgery may be a better choice for
      achieving successful union while reducing the risk of re-fracture or infection.

PMID- 17195934
TI  - Aftertreatment of malleolar fractures following ORIF -- functional compared to
      protected functional in a vacuum-stabilized orthesis: a randomized controlled
      trial.
AB  - In a monocenter randomized controlled trial, 45 patients with isolated malleolar
      fracture type OTA/AO 44 A1-B2 undergoing ORIF were allocated randomly to a
      postoperative treatment either with a vacuum-stabilized orthesis with prescribed
      full weight bearing after the second week (23 patients) (orthesis group -- OG) or
      with functional aftertreatment with partial weight bearing of 15 kg for 6 weeks
      (22 patients) (control group -- CG). Outcomes were compared at 6- and 10-week
      follow-up examinations. The Olerud and Molander ankle (OMA) score, ankle
      swelling, usage of crutches, range of motion, Short Form 12, patient-reported
      visual analogue scales (VAS) (pain, comfort, walking confidence) and time to
      return to work were evaluated. All patients of OG showed reduced swelling at
      discharge. The median OMA scores after 6 weeks were 42 and 42.5 (p = 0.46) and
      after 10 weeks 69 and 72 (p = 0.55) in the OG and CG, respectively. The time to
      achieve secure walking capacity was reduced by 1 day (p = 0.03) in the OG. After
      ORIF of simple malleolar fractures, patients with a vacuum-stabilized orthesis
      can bear full weight 2 weeks postoperatively. This group experienced no adverse
      events. Postoperative swelling was significantly reduced and of the ability to
      walk on stairs confidently was shorter as compared to a functional aftertreatment
      without any external stabilization of the ankle.

PMID- 17195935
TI  - Mother-to-child transmission of hepatitis C virus infection in Barcelona, Spain:
      a prospective study.

PMID- 17195937
TI  - Rhabdomyolysis and acute renal failure in a child with Salmonella enteritidis
      gastroenteritis.
AB  - We report on an 11-year-old boy who developed rhabdomyolysis and acute renal
      failure following Salmonella enteritidis gastroenteritis. Rhabdomyolysis should
      be considered as a potentially fatal complication in patients with Salmonella
      gastroenteritis.

PMID- 17195936
TI  - Effect of pneumococcal vaccination on otitis media with effusion in children
      older than 1 year.
AB  - Pneumococcal vaccines may be effective in preventing or decreasing the burden of
      disease related to otitis media. In study reported here, we investigated the
      effectiveness of pneumococcal vaccination on otitis media with effusion (OME) in
      children (n = 383 children aged 1-7 years) with a history of recurrent otitis
      media within the framework of a randomized double blind placebo controlled trial.
      Children were randomized to be immunized with either a 7-valent pneumococcal
      conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine,
      or by hepatitis A or B vaccines. The proportion of children diagnosed with OME at
      the scheduled follow-up visits--7, 14, 20 and 26 months after randomization--was
      then calculated. OME was diagnosed according to an algorithm combining
      tympanometry and otoscopy. The percentage of children diagnosed with OME was
      similar in the pneumococcal vaccination group and control group at both baseline
      and the follow-up visits at 7, 14, 20 and 26 months--52.9 versus 52.7, 44.9
      versus 44.2, 34.9 versus 31.5, 40.8 versus 32.2 and 31.4 versus 26.1,
      respectively (corresponding to p-values of 0.96, 0.89, 0.51, 0.13 and 0.36,
      respectively). We conclude that the combined pneumococcal conjugate and the
      polysaccharide vaccination have no beneficial effect on OME in children aged 1
      year or older with a history of recurrent otitis media. Therefore, these
      vaccinations are not indicated in the prevention of OME in these children.

PMID- 17195938
TI  - Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause
      of parainfectious rhabdomyolysis.
AB  - Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168),
      is a recently delineated neurogenetic disease causing recurrent episodes of
      rhabdomyolysis; prevention and early diagnosis of rhabdomyolysis should be part
      of the clinical management of the disease.

PMID- 17195939
TI  - Prevention of unnecessary contralateral exploration using the silk glove sign
      (SGS) in pediatric patients with unilateral inguinal hernia.
AB  - INTRODUCTION: The issue of how to best detect an occult contralateral patent
      processus vaginalis (PPV) in a child who presents with a unilateral inguinal
      hernia has been debated for over 50 years. The ideal diagnostic tool would
      eliminate unnecessary contralateral exploration. The "silk glove sign" (SGS) or
      palpating the processus vaginalis over the pubic tubercle is the simplest
      preoperative diagnostic test for diagnosing contralateral PPV. MATERIALS AND
      METHODS: In an attempt to determine whether it is possible with the SGS to
      evaluate the contralateral inguinal region to ascertain if a contralateral PPV is
      present, we prospectively reviewed our own experience at a single institution
      within a 5-year period. Between January 2001 and December 2005, 1,040 pediatric
      patients with inguinal hernias were treated by one surgeon at Chang Gung
      Children's Hospital. Of these, with the exception of 120 patients with clinical
      bilateral inguinal hernia, 920 patients (746 boys and 174 girls) with unilateral
      inguinal hernia underwent examination. A total of 180 (19.8%), of whom 154 were
      boys and 26 were girls, were SGS positive and underwent bilateral surgery.
      RESULTS: A PPV or true hernia sac was found in 164 (91.1%). The sensitivity of
      diagnosis by SGS was 93.1%. In the remaining 740 SGS-negative patients, a
      metachronous hernia developed in 20. The specificity of diagnosis by SGS was
      97.3%. The SGS could detect a contralateral hernia in patients regardless of age,
      but the accuracy of detection in girls was lower than in boys. CONCLUSION: SGS is
      a simple, noninvasive method of preoperative evaluation of the groins. Accuracy
      through repeated and careful examination is about 91%. Our policy of
      contralateral exploration based on the SGS has been reliable in minimizing
      unnecessary surgical exploration.

PMID- 17195941
TI  - Idiopathic spontaneous hemoperitoneum during pregnancy.
AB  - We present a case of a 24-year old, otherwise healthy, primigravida that was
      admitted at term with severe abdominal pain, hemoperitoneum, hypovolemic shock
      and severe fetal bradycardia. There was no history of abdominal trauma. Due to
      suspected fetal distress and placental abruption an emergency cesarean section
      was performed. Careful exploration of the abdominal cavity, uterus and placenta
      did not reveal the origin of hemorrhage, placental abruption was ruled out.
      Idiopathic spontaneous hemoperitoneum is a rare and life threatening condition.
      The origin of the hemorrhage often remains obscure, even after a thorough workup.
      To the best of our knowledge, this is the first case of idiopathic spontaneous
      hemoperitoneum reported in a pregnant patient at term. A review of the literature
      was undertaken.

PMID- 17195940
TI  - Glutathione synthesis is regulated by nitric oxide in Medicago truncatula roots.
AB  - Glutathione (GSH) is one of the main antioxidants in plants. Legumes have the
      specificity to produce a GSH homolog, homoglutathione (hGSH). We have
      investigated the regulation of GSH and hGSH synthesis by nitric oxide (NO) in
      Medicago truncatula roots. Analysis of the expression level of gamma
      glutamylcysteine synthetase (gamma-ECS), glutathione synthetase (GSHS) and
      homoglutathione synthetase (hGSHS) after treatment with sodium nitroprusside
      (SNP) and nitrosoglutathione (GSNO), two NO-donors, showed that gamma-ecs and
      gshs genes are up regulated by NO treatment whereas hgshs expression is not.
      Differential accumulation of GSH was correlated to gene expression in SNP-treated
      roots. Our results provide the first evidence that GSH synthesis pathway is
      regulated by NO in plants and that there is a differential regulation between
      gshs and hgshs in M. truncatula.

PMID- 17195942
TI  - Relevance of phenylalanine 216 in the affinity of Saccharomyces cerevisiae
      phosphoenolpyruvate carboxykinase for Mn(II).
AB  - Saccharomyces cerevisiae phosphoenolpyruvate (PEP) carboxykinase catalyzes the
      reversible formation of oxaloacetate and adenosine triphosphate from PEP,
      adenosine diphosphate and carbon dioxide, and uses Mn(2+) as the activating metal
      ion. Comparison with the crystalline structure of homologous Escherichia coli PEP
      carboxykinase [Tari et al. (1997) Nature Struct. Biol. 4, 990-994] shows that
      Lys(213) is one of the ligands to Mn(2+) at the enzyme active site. Coordination
      of Mn(2+) to a lysyl residue is not common and suggests a low pK (a) value for
      the epsilon-NH(2) group of Lys(213). In this work, we evaluate the role of
      neighboring Phe(216) in contributing to provide a low polarity microenvironment
      suitable to keep the epsilon-NH(2) of Lys(213) in the unprotonated form. Mutation
      Phe216Tyr shows that the introduction of a hydroxyl group in the lateral chain of
      the residue produces a substantial loss in the enzyme affinity for Mn(2+),
      suggesting an increase of the pK (a) of Lys(213). In agreement with this
      interpretation, theoretical calculations indicate an alkaline shift of 2.8 pH
      units in the pK (a) of the epsilon-amino group of Lys(213) upon Phe216Tyr
      mutation.

PMID- 17195943
TI  - Role of endogenous ghrelin in growth hormone secretion, appetite regulation and
      metabolism.
AB  - Ghrelin, a 28-amino acid hormone that is acylated post-translation, is the
      endogenous ligand for the growth hormone (GH) secretagogue (GHS) receptor (GHS
      R). The highest concentrations of ghrelin are found in the stomach; however
      ghrelin peptide is also present in hypothalamic nuclei known to be important in
      the control of GH and feeding behavior. Exogenous ghrelin potently stimulates
      pituitary GH release through a mechanism that is dependent, in part, on
      endogenous GH-releasing hormone. Whether endogenous ghrelin plays a role in the
      control of GH secretion and growth is not clear and ghrelin deficient animals
      appear to grow normally. In contrast, experimental animal and clinical data
      suggest that abnormalities in GHS-R signaling could impact growth. Ghrelin or
      other GHS are clinically useful for GH-testing and limited data suggest that they
      might be useful in the treatment of some patients with GH deficiency. Substantial
      data have implicated ghrelin as an important regulator of feeding behavior and
      energy equilibrium. Ghrelin has a potent orexigenic effect in both animals and
      humans and this effect is mediated through hypothalamic neuropeptide Y (NPY) and
      Agouti-related peptide (AgRP). Appetite simulation coupled with other metabolic
      effects promotes weight gain during chronic treatment with ghrelin. These
      metabolic effects are in part mediated through an increase in respiratory
      quotient (VQ). Presence of ghrelin appears to be necessary for the development of
      obesity in some animal models. Whether abnormalities in ghrelin signaling are
      involved in human obesity is not yet known.

PMID- 17195944
TI  - Up-regulation of CD95 (Apo-1/Fas) is associated with spermatocyte apoptosis
      during the first round of spermatogenesis in the rat.
AB  - Apoptosis plays a major role in controlling both the rate of sperm production and
      chromosomal abnormalities in adult male testes. However, little is known on the
      mechanisms controlling induction and execution of apoptosis under physiological
      conditions. In this work we have uncovered a major role for the cell death
      receptor Fas in both the extrinsic and intrinsic pathways in normal germ cell
      apoptosis. We show here that Fas levels increased significantly in a group of
      germ cell in 25 d old rats, which were identified as spermatocytes and only a few
      spermatogonia. In addition, we show that isolated spermatocytes expressing high
      levels of Fas display activation of caspase-8, -9, -3, -6 and -2, as well as
      increased levels of intracellular calcium and decreased pH, which coincides with
      stabilization of p53, and transcriptional activation of PUMA and Fas. Therefore,
      our data strongly suggests that transcriptional up regulation of Fas could
      predispose a group of spermatocytes to Fas ligand triggering apoptosis by the
      extrinsic and intrinsic pathway.

PMID- 17195946
TI  - Electrokinetic measurements of dielectric properties of membrane for apoptotic HL
      60 cells on chip-based device.
AB  - The specific membrane capacitance and conductance of mammalian cells reflect the
      surface morphological complexities and barrier functions of cell membrane,
      respectively, and could potentially respond to cell physiological and
      pathological changes in a measurable manner. In this study, an electrokinetic
      system was developed by using negative dielectrophoretic force (nDEP force)
      assisted positioning and electroroation (ROT) measurement. Numerical simulations
      regarding the geometric model of the electrode were performed primarily for the
      electric field analysis. The dielectric responses of membrane for apoptotic HL-60
      cells induced by bufalin were detected. The membrane capacitance of the cells was
      found to fall from an initial value of 15.6 +/- 0.9 mF/cm(2) to 6.4 +/- 0.6
      mF/cm(2) after a 48 h treatment with 10 nM bufalin. However, the membrane
      conductance remained almost constant at (2.25 +/- 1.1) x 10(3) S/m(2) during the
      first 12 h of bufalin treatment and then increased distinctly to (4.2 +/- 1.3) x
      10(3) S/m(2) thereafter. Scan electron microscopy (SEM) studies of the cells
      revealed a decreased complexity in cell membrane morphology following bufalin
      treatments, suggesting that the observed changes in the membrane capacitance was
      dominated by the alterations of cell surface structures. The results demonstrate
      that the ROT technique gives a quantitative analysis of the toxic damage by
      chemicals to cells and can be exploited in the testing and development of new
      pharmaceuticals and active cell agents.

PMID- 17195948
TI  - Extradyadic sexual relationships in Norway.
AB  - The purpose of this research was to study the occurrence of extradyadic sexual
      relationships among Norwegians. We examined what background factors were
      associated with this type of relationship, and to what extent condoms were used.
      In 2002, a random sample of 9,852 Norwegians between the ages of 18 and 49 were
      asked to participate in an anonymous self-administered questionnaire survey on
      sexual behavior. A total of 3387 persons responded (1386 men, 1993 women, and 8
      who did not indicate their gender), yielding a response rate of 34%. Of the 2807
      participants who had ever been married or cohabited, 29% of the men and 23% of
      the women reported experience with extradyadic sexual relationships at some point
      during their lives. Sixteen percent of the men and 11% of the women reported
      extradyadic sex during their current marriage/cohabiting relationship. Women were
      more emotionally attached to the extradyadic partner than men. Factors that
      predicted occurrence of extradyadic sexual relationships were age, number of
      years married/cohabiting, number of sex partners, and sexual orientation. In
      addition, there was a correlation between low self-esteem and extradyadic sexual
      experience. About 50% of the participants reported no use of contraception during
      the most recent intercourse with an extradyadic partner. In conclusion, men's
      extradyadic partner seems most often to be a casual partner, whereas women prefer
      someone they already know. The choice of extradyadic partner is most likely
      associated with use of STI protection.

PMID- 17195945
TI  - Pharmacokinetic and safety study of weekly irinotecan and oral capecitabine in
      patients with advanced solid cancers.
AB  - BACKGROUND: Capecitabine and irinotecan have demonstrated in vitro synergistic
      anti-cancer activity, and both are substrates for carboxyl esterases (CES). We
      conducted a study to identify a safe dose and potential drug-drug interactions of
      this combination. METHODS: This was an open-label phase I dose escalation trial.
      Irinotecan was given as a 30 min infusion on days 1 and 8, and capecitabine on
      days 1-14 of a 21-day cycle. Plasma for pharmacokinetic analyses was drawn on
      days 1 and 8. RESULTS: Forty-seven patients with advanced solid tumors received
      202 cycles of chemotherapy in 6 dose cohorts. At the highest dose tested, 1 of 3
      patients developed fatal neutropenia and gram-negative sepsis. At dose level 5
      (100/2000), 2 of 28 patients developed cycle 1 DLT-grade 3 diarrhea/vomiting, and
      grade 3 diarrhea. Responses were observed in 9 of 35 (5 of 9 ovarian cancer)
      evaluable patients. The AUC((0-last)) of irinotecan, SN-38G, and APC were similar
      on days 1 and 8. However, SN-38 T(max) was longer on Day 8 (0.88 h vs. 1.23 h, p
      = 0.012). While SN-38 AUC((0-last)) was lower on day 8 by 35%, this was not
      statistically significant (p = 0.123). CONCLUSIONS: Capecitabine results in a
      significantly delayed conversion of irinotecan to SN-38, suggesting drug-drug
      interaction at the level of CES. This suggests caution should be used when
      irinotecan is combined with substrates of CES, and warrants further study. The
      combination of irinotecan and capecitabine is safe and well tolerated at
      100/2000, and warrants further evaluation in ovarian and breast cancer.

PMID- 17195949
TI  - Stress sensitization and adolescent depressive severity as a function of
      childhood adversity: a link to anxiety disorders.
AB  - The goal of the present study was to determine whether exposure to adversity in
      childhood contributes to a differential threshold at which stressful life events
      provoke depressive reactions in adolescence. In addition, to address empirical
      and conceptual questions about stress effects, the moderating effect of anxiety
      disorder history was also explored. This examination was conducted in a sample of
      816 children of depressed and nondepressed mothers, who were followed from birth
      to age 15. Information on adversities experienced in childhood was collected both
      from mothers during the first five years of their youth's life and from the
      youths themselves at age 15, and included information on the mother's
      relationship with her partner, maternal psychopathology, as well as youth
      reported abuse. Results indicated that youths with both greater exposure to
      adversity in childhood and a history of an anxiety disorder displayed increased
      depressive severity following low levels of episodic stress compared to youths
      with only one or neither of these risk factors. The results are speculated to
      reflect the possibility that early anxiety disorders associated with exposure to
      adversity in childhood may be a marker of dysregulated stress responses, and may
      help to account for the comorbidity of depression and anxiety in some
      individuals.

PMID- 17195951
TI  - What is the social impact of ADHD in girls? A multi-method assessment.
AB  - This study explores the social impact of ADHD, with and without opposition
      defiant behaviour (ADHD+ODD (n= 22) and ADHD-only (n= 18)), in 9- to 12- year old
      girls compared to girls without ADHD (n= 40). Girls played a computer game
      involving simulated players, and mothers and teachers completed rating scales. In
      general, mothers and teachers saw girls with ADHD+ODD as more overtly and
      relationally aggressive and less prosocial than girls with ADHD-only, who were
      seen as more overtly and relationally aggressive and less prosocial than control
      girls. On the computer game, girls with ADHD+ODD were more overtly aggressive,
      more directly relationally aggressive, and showed less skilled behaviour than the
      other groups. Girls with ADHD-only showed less covert, indirect relational
      aggression and more socially awkward interactions than girls in the control group
      on the computer game. In all, the results indicate that girls with ADHD, with and
      without ODD behaviour, engage in socially detrimental behaviours.

PMID- 17195950
TI  - Self-handicapping prior to academic-oriented tasks in children with attention
      deficit/hyperactivity disorder (ADHD): medication effects and comparisons with
      controls.
AB  - Examined self-handicapping prior to academic-oriented tasks in children with and
      without ADHD and examined whether stimulant medication influenced self
      handicapping. Participants were 61 children ages 6 to 13, including 22 children
      with ADHD tested after taking a placebo, 21 children with ADHD tested after
      taking stimulant medication, and 18 non-ADHD controls. Participants completed
      three measures of self handicapping and also completed self-evaluations of their
      performance. Results showed greater self handicapping and more positive self
      evaluations in children with ADHD than in controls regardless of medication
      condition. Findings suggest children with ADHD may use self handicapping to
      ameliorate the effects of experiencing high rates of academic failure.

PMID- 17195952
TI  - A cognitive neuroscience approach to studying the role of overconfidence in
      problem gambling.
AB  - Research on the neural correlates of decision making in gambling tasks may be
      informative for understanding problem gambling. The present study explored
      confidence and overconfidence using magnetoencephalography (MEG) to measure brain
      activity during a judgment task. Nineteen undergraduates who self-identified as
      frequent gamblers (average age 19.7 years; 5 females, 14 males) participated in
      this study. Participants first completed the DIGS (Winters, Specker &
      Stinchfield, 2002), a measure of gambling pathology. They then engaged in a
      behavioral task of confidence assessment, wherein they answered two-alternative
      trivia questions and estimated the probability that each answer was correct. In a
      subsequent MEG task, they viewed the questions and a target answer, and indicated
      with a button press whether the target matched the correct answer. Confidence was
      directly related to activity in the right prefrontal cortex. Matching and
      mismatching targets were associated with activity in the medial occipital cortex
      and left supramarginal gyrus, respectively. An interaction of pathology and
      match/mismatch was observed in the right inferior occipital-temporal junction
      region, showing more activity following a mismatch in non-problem gamblers, but
      not in problem gamblers. Implications of the results for understanding of top
      down modulation and attentional systems are discussed in relation to gambling
      behavior.

PMID- 17195953
TI  - Molecular epidemiologic analysis of group A rotaviruses in adults and children
      with diarrhea in Wuhan city, China, 2000-2006.
AB  - To compare epidemiologic features and genetic characteristics of group A
      rotaviruses causing diarrhea in children and adults, a survey was conducted in
      Wuhan, China, during the period of Dec. 2000-May 2006. A total of 3839 stool
      specimens from diarrheal patients from eight hospitals were analyzed. Winter
      seasonality was observed for rotavirus diarrhea in both adults and children,
      showing overall rotavirus-positive rates of 9.0 and 23.9%, respectively.
      Throughout the study period, G3 was the most frequent G serotype in both adults
      and children (detection rates 86.2 and 87.8%, respectively), and was mostly
      associated with VP4 genotype P[8], VP 6 genotype II (subgroup II), and NSP4
      genotype B. G3 rotaviruses were differentiated into eight electropherotypes,
      among which seven types were found in specimens from both adults and children.
      VP7 gene sequences of G3 rotaviruses from adults and children (6 and 4 strains,
      respectively), detected in different years and different hospitals, showed
      extremely high sequence identities (99-100%) to each other and to a few G3
      rotavirus strains reported in Asia. However, lower sequence identities (82-96%)
      were observed to most of the human and animal G3 rotaviruses reported so far,
      including some Chinese strains. These findings indicate that in Wuhan, China,
      epidemic and genetic features of rotaviruses are similar in adults and children,
      and it has been suggested that G3 rotaviruses that might have originated from the
      same rotavirus were circulating among children and adults as prevailing viruses.
      In this study, two rotavirus strains, G9P[8] strain L169, derived from an adult,
      and G4P[6] strain R479, derived from a child, were isolated and genetically
      analyzed. The VP7 gene of L169 belongs to a major lineage of G9 rotaviruses that
      are globally widespread, but is distinct from G9 rotaviruses reported previously
      in China. The strain R479 had a VP7 gene which was divergent from most G4 human
      rotaviruses and showed an unusual dual subgroup specificity, I + II. The R479 VP6
      gene does not belong to the main clusters of subgroup I and II rotaviruses
      phylogenetically, but is related to those of the porcine rotaviruses and some
      unusual human rotaviruses represented by the RMC321 strain isolated in eastern
      India.

PMID- 17195954
TI  - Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika
      viruses.
AB  - Many members of the genus Flavivirus are the agents of important diseases of
      humans, livestock, and wildlife. Currently, no complete genome sequence is
      available for the three African viruses, Bagaza, Zika, and Kedougou viruses, each
      representing a distinct virus subgroup according to the latest virus
      classification. In this study, we obtained a complete genome sequence of each of
      those three viruses and characterized the open reading frames (ORFs) with respect
      to gene sizes, cleavage sites, potential glycosylation sites, distribution of
      cysteine residues, and unique motifs. The sequences of the three viruses were
      then scanned across the entire length of the ORF against available sequences of
      other African flaviviruses and selected reference viruses for genetic
      relatedness. The data collectively indicated that Kedougou virus was close to
      dengue viruses but nonetheless distinct, while Bagaza virus shared genetic
      relatedness with West Nile virus in several genomic regions. In the non-coding
      regions, it was found that a particular organizational pattern of conserved
      sequences in the 3' terminal region generally correlated with the current virus
      grouping.

PMID- 17195956
TI  - Molecular analysis of a full-length sequence of a new yam badnavirus from
      Dioscorea sansibarensis.
AB  - Badnavirus-like particles were observed by ISEM in viral preparations from yam
      (Dioscorea sansibarensis) leaves from Benin. Use of the viral preparation as
      template for PCR amplification with badnavirus-specific primers gave rise to a
      579-bp product with most nucleotide identity (70.8%) to Dioscorea alata
      bacilliform virus (DaBV, Accession numbers X94575-X94582), the only other yam
      badnavirus sequenced to date. A full-length badnavirus sequence was generated,
      which consisted of 7261 nucleotides with a typical Badnavirus genome
      organisation. The full-length sequence shared most identity (61.9%) to DaBV
      (Accession numbers X94575-X94582) and hence represents a member of a new
      badnavirus species termed Dioscorea sansibarensis bacilliform virus (DsBV).

PMID- 17195957
TI  - Circulation of a type 1 recombinant vaccine-derived poliovirus strain in a
      limited area in Romania.
AB  - After intensive immunisation campaigns with the oral polio vaccine (OPV) as part
      of the Global Polio Eradication Initiative, poliomyelitis due to wild viruses has
      disappeared from most parts of the world, including Europe. Here, we report the
      characterization of a serotype 1 vaccine-derived poliovirus (VDPV) isolated from
      one acute flaccid paralysis (AFP) case with tetraplegia and eight healthy
      contacts belonging to the same small socio-cultural group having a low vaccine
      coverage living in a small town in Romania. The genomes of the isolated strains
      appeared to be tripartite type 1/type 2/type 1 vaccine intertypic recombinant
      genomes derived from a common ancestor strain. The presence of 1.2% nucleotide
      substitutions in the VP1 capsid protein coding region of most of the strains
      indicated a circulation time of about 14 months. These VDPVs were thermoresistant
      and, in transgenic mice expressing the human poliovirus receptor, appeared to
      have lost the attenuated phenotype. These results suggest that small populations
      with low vaccine coverage living in globally well-vaccinated countries can be the
      origin of VDPV emergence and circulation. These results reaffirm the importance
      of active surveillance for acute flaccid paralysis and poliovirus in both polio
      free and polio-endemic countries.

PMID- 17195955
TI  - Variability of the PreS1/PreS2/S regions of hepatitis B virus in Hungary.
AB  - Infection with the hepatitis B virus can occur perinatally, parenterally, or
      sexually, and it can cause acute or chronic liver diseases. Phylogenetic analysis
      of the virus has led to its classification into eight genotypes (A-H), which show
      a characteristic worldwide distribution. The aim of this study was to reveal the
      HBV genotypes present in Hungary and to investigate a nosocomial and an
      intrafamilial outbreak. The collected samples were tested by nested PCR, and a
      650-nucleotide-long segment of the preS1/preS2/S region was sequenced. As no
      previous genotype data were available from Hungary, sera of 24 HBsAg-positive
      patients were collected from different regions of the country. They also served
      as control samples for the molecular epidemiologic study. Nineteen of them
      carried genotype D of hepatitis B virus, and five of them carried genotype A.
      Twenty-nine patients from a haemato-oncology unit were affected in a nosocomial
      outbreak. The patients had haematological and/or oncological diseases, most of
      them were immunosuppressed. In twenty-eight cases, based on phylogenetic analysis
      of the viruses, there was presumably a common source of infection, and an
      epidemiological investigation showed that the infections seemed to be hospital
      acquired. In the intrafamilial outbreak, two asymptomatic carrier children
      infected their foster mother. The three sequences were totally identical.

PMID- 17195958
TI  - Role of HPV E6 proteins in preventing UVB-induced release of pro-apoptotic
      factors from the mitochondria.
AB  - Apoptotic elimination of UV-damaged cells from the epidermis is an important step
      in preventing both the emergence and expansion of cells with carcinogenic
      potential. A pivotal event in apoptosis is the release of apoptogenic factors
      from the mitochondria, although the mechanisms by which the different proteins
      are released are not fully understood. Here we demonstrate that UV radiation
      induced the mitochondrial to nuclear translocation of apoptosis inducing factor
      (AIF) in normal skin. The human papillomavirus (HPV) E6 protein prevented release
      of AIF and other apoptotic factors such as cytochrome c and Omi from mitochondria
      of UV-damaged primary epidermal keratinocytes and preserved mitochondrial
      integrity. shRNA silencing of Bak, a target for E6-mediated proteolysis,
      demonstrated the requirement of Bak for UV-induced AIF release and mitochondrial
      fragmentation. Furthermore, screening non-melanoma skin cancer biopsies revealed
      an inverse correlation between HPV status and AIF nuclear translocation. Our
      results indicate that the E6 activity towards Bak is a key factor that promotes
      survival of HPV-infected cells that facilitates tumor development.

PMID- 17195959
TI  - Clinicopathological roles of alterations of tumor suppressor gene p16 in
      papillary thyroid carcinoma.
AB  - BACKGROUND: Alterations of the p16 gene are common in human cancers, but their
      roles in thyroid cancers have not been clearly defined. The aim of the present
      study was to investigate the clinicopathological roles of the p16 gene in
      papillary thyroid carcinoma (PTC). METHODS: p16 gene alterations were
      investigated in 44 patients with PTC (9 men, 35 women) by immunohistochemistry,
      reverse transcriptase-polymerase chain reaction and methylation-specific
      polymerase chain reaction. The findings were correlated with their
      clinicopathological features. RESULTS: p16 protein expression, mRNA alterations,
      and promoter methylation were detected in 89% (n = 39), 77% (n = 33), and 41% (n
      = 18) of patients with PTC, respectively. There was no marked relationship
      between p16 protein expression, mRNA alteration, and promoter methylation. In
      follicular variant of PTC (FVPTC), there was a frequent lack of p16 protein
      expression and promoter methylation. PTCs showing p16 promoter methylation were
      often associated with a high AMES (age, metastasis to distant sites,
      extrathyroidal invasion, size) risk group and advanced pTNM (tumor-lymph node
      metastasis) stages. CONCLUSIONS: p16 gene alterations are common and correlate
      with histological features and biological aggressiveness in PTC, suggesting that
      they might play an important role in its pathogenesis.

PMID- 17195960
TI  - Covariate heterogeneity in meta-analysis: criteria for deciding between meta
      regression and individual patient data.
AB  - Meta-analyses of clinical trials are increasingly seeking to go beyond estimating
      the effect of a treatment and may also aim to investigate the effect of other
      covariates and how they alter treatment effectiveness. This requires the
      estimation of treatment-covariate interactions. Meta-regression can be used to
      estimate such interactions using published data, but it is known to lack
      statistical power, and is prone to bias.The use of individual patient data can
      improve estimation of such interactions, among other benefits, but it can be
      difficult and time-consuming to collect and analyse. This paper derives, under
      certain conditions, the power of meta-regression and IPD methods to detect
      treatment-covariate interactions. These power formulae are shown to depend on
      heterogeneity in the covariate distributions across studies. This allows the
      derivation of simple tests, based on heterogeneity statistics, for comparing the
      statistical power of the analysis methods.

PMID- 17195961
TI  - Regulation of human lymphocyte proliferation by fatty acids.
AB  - In the present study, the effect of increasing concentrations of palmitic (PA,
      C16:0), stearic (SA, C18:0), oleic (OA, C18:1, n-9), linoleic (LA, C18:2n-6),
      docosahexaenoic (DHA, C22:6 n-3) and eicosapentaenoic (EPA, C20:5 n-3) acids on
      lymphocyte proliferation was investigated. The maximal non-toxic concentrations
      of these fatty acids for human lymphocytes in vitro were determined. It was also
      evaluated whether these fatty acids at non-toxic concentrations affect IL-2
      induced lymphocyte proliferation and cell cycle progression. OA and LA at 25
      microM increased lymphocyte proliferation and at higher concentrations (75 microM
      and 100 microM) inhibited it. Both fatty acids promoted cell death at 200 microM
      concentration. PA and SA decreased lymphocyte proliferation at 50 microM and
      promoted cell death at concentrations of 100 microM and above. EPA and DHA
      decreased lymphocyte proliferation at 25 and 50 microM being toxic at 50 and 100
      microM, respectively. PA, SA, DHA and EPA decreased the stimulatory effect of IL
      2 on lymphocyte proliferation, increasing the percentage of cells in G1 phase and
      decreasing the proportion of cells in S and G2/M phases. OA and LA caused an even
      greater pronounced effect. The treatment with all fatty acids increased neutral
      lipid accumulation in the cells but the effect was more pronounced with PA and
      DHA. In conclusion, PA, SA, DHA and EPA decreased lymphocyte proliferation,
      whereas OA and LA stimulated it at non-toxic concentrations.

PMID- 17195962
TI  - The FXIIIVal34Leu, common and risk factors of venous thrombosis in early middle
      age Costa Rican patients.
AB  - In this study, eight common polymorphisms associated with venous thrombosis (VT)
      and thrombophilia factors were analyzed in a Costa Rican case-control study. With
      the use of polymerase chain reaction (PCR) methods the polymorphisms were
      detected in 120 patients and 133 controls (mean age <40 years old). It was
      concluded that a high level of fibrinogen, antiphospholipid antibodies, family
      history, and the genotype 34LeuLeu of FXIII OR 0.42 (0.20-0.89) showed a
      significant effect on the risk of VT. Associations between the risk of VT and
      genetic polymorphisms have been established. Some of these polymorphisms are
      highly prevalent in Caucasians, but there is a significant geographic variation
      in their prevalence among different populations. The results of this study
      support the protective effect of FXIII Val34Leu polymorphism in VT. These
      findings are consistent with previous reports that included other populations.

PMID- 17195963
TI  - T-Cell epitope discovery for variola and vaccinia viruses.
AB  - Variola major, the causative agent of smallpox, afflicted mankind throughout
      history until the worldwide World Health Organisation WHO vaccination campaign
      successfully eradicated the disease. Unfortunately, recent concerns about
      bioterrorism have renewed scientific interest in this virus. One essential
      component of our biodefense and preparedness efforts is an understanding of
      poxvirus immunity. To this end a number of laboratories have sought to discover T
      and B-Cell epitopes from select agents such as variola virus. This review
      focuses on the efforts to identify CD8(+) T-Cell epitopes from poxviruses as a
      means to develop new vaccines and therapeutics. A wide variety of techniques have
      been employed by several research groups to provide complementary information
      regarding cellular immune responses to poxviruses. In the last several years well
      over 100 T-Cell epitopes have been identified and the work rapidly continues. The
      information gleaned from these studies will not only give us a greater
      understanding of immunity to variola virus and other viruses, but also provide a
      foundation for next generation vaccines and additional tools with which to study
      host-pathogen interactions.

PMID- 17195965
TI  - Initial experience with the Cardiva Boomerang vascular closure device in
      diagnostic catheterization.
AB  - OBJECTIVES: The authors studied the safety and efficacy of the Cardiva Boomerang
      vascular closure device in patients undergoing diagnostic cardiac
      catheterization. BACKGROUND: Conventional vascular closure devices (sutures,
      collagen plugs, or metal clips) have been associated with catastrophic
      complications including arterial occlusion and foreign body infections;
      furthermore, they cannot be utilized in patients with peripheral vascular disease
      or vascular access site in a vessel other than the common femoral artery. The
      Cardiva Boomerang device facilitates vascular hemostasis without leaving any
      foreign body behind at the access site, can be used in peripheral vascular
      disease, and can be used in vessels other than the common femoral artery METHODS:
      A total of 96 patients undergoing transfemoral diagnostic cardiac catheterization
      were included in this study, including 25 (26%) patients with contraindications
      to conventional closure devices. Femoral angiography was performed prior to
      deployment of the Cardiva Boomerang closure device. Patients were ambulated at 1
      hr after hemostasis was achieved. RESULTS: The device was successfully deployed
      and hemostasis achieved with the device alone in 95 (99%) patients. The device
      failed to deploy in 1 (1%) patient and required conversion to standard manual
      compression. Minor complications were observed in 5 (5%) patients. No patients
      experienced major complications including femoral hematoma > 4 cm, red blood cell
      transfusion, retroperitoneal bleed, arteriovenous fistula, pseudoaneurysm,
      infection, arterial occlusion, or vascular surgery. CONCLUSIONS: The Cardiva
      Boomerang device is safe and effective in patients undergoing diagnostic cardiac
      catheterization using the transfemoral approach, facilitating early ambulation
      with low rates of vascular complications.

PMID- 17195964
TI  - The impact of renal insufficiency on patients' outcomes in emergent angioplasty
      for acute myocardial infarction.
AB  - BACKGROUND: Renal insufficiency (RF) was shown to be associated with a worsened
      prognosis following acute myocardial infarction (AMI). OBJECTIVES: The authors
      analyzed the outcomes of AMI patients with impaired renal function tests treated
      using primary percutaneous coronary intervention (PCI), to determine factors
      associated with increased mortality risk. METHODS: This study included 558
      consecutive AMI patients treated using primary PCI between January 2001 and June
      2005. The authors compared outcome results according to glomerular filtration
      rate (GFR). An abbreviated equation was used to calculate GFR. Patients were
      grouped as follow: normal (> or =90 mL/min/1.73 m(2)), mildly impaired (60-89
      mL/min/1.73 m(2)), moderately impaired (30-59 mL/min/1.73 m(2)), and severely
      impaired GFR (< 30 mL/min/1.73 m(2)). RESULTS: There was a stepwise increase in
      30-day mortality among patients with normal, mildly, moderately, and severely
      impaired RF: 2.1%, 3.7%, 8.2%, and 22.2%, respectively (P = 0.004). Seventeen out
      of the 324 with any degree of RF died within 1 month [5.3%] of these nine
      patients [53%] died because of cardiac cause. Univariate correlation analysis,
      factors associated with an increased risk of 1 month mortality included: age > 75
      years, left ventricular ejection fraction < 35%, lower GFR, killip class > 1,
      multivessel coronary artery disease, failure to achieve TIMI flow grade = 3, the
      occurrence of no-reflow, IABP use, lack of administration of anti GP 2b/3a. The
      amount of contrast media used during the procedure [mL/Kg] as well as renal
      function deterioration were also associated with increased mortality.
      CONCLUSIONS: Clinical and angiographic parameters collected before and during PCI
      can be used to predict 30-day mortality among AMI patients with RF. Findings
      indicate that in the setting of contemporary catheter-based reperfusion strategy
      for AMI, the extent of coronary artery disease, measures of PCI complexity, and
      degree of renal impairment prior/following the procedure are altogether related
      to mortality.

PMID- 17195966
TI  - Allelopathy in crop/weed interactions--an update.
AB  - Since varietal differences in allelopathy of crops against weeds were discovered
      in the 1970s, much research has documented the potential that allelopathic crops
      offer for integrated weed management with substantially reduced herbicide rates.
      Research groups worldwide have identified several crop species possessing potent
      allelopathic interference mediated by root exudation of allelochemicals. Rice,
      wheat, barley and sorghum have attracted most attention. Past research focused on
      germplasm screening for elite allelopathic cultivars and the identification of
      the allelochemicals involved. Based on this, traditional breeding efforts were
      initiated in rice and wheat to breed agronomically acceptable, weed-suppressive
      cultivars with improved allelopathic interference. Promising suppressive crosses
      are under investigation. Molecular approaches have elucidated the genetics of
      allelopathy by QTL mapping which associated the trait in rice and wheat with
      several chromosomes and suggested the involvement of several allelochemicals.
      Potentially important compounds that are constitutively secreted from roots have
      been identified in all crop species under investigation. Biosynthesis and
      exudation of these metabolites follow a distinct temporal pattern and can be
      induced by biotic and abiotic factors. The current state of knowledge suggests
      that allelopathy involves fluctuating mixtures of allelochemicals and their
      metabolites as regulated by genotype and developmental stage of the producing
      plant, environment, cultivation and signalling effects, as well as the chemical
      or microbial turnover of compounds in the rhizosphere. Functional genomics is
      being applied to identify genes involved in biosynthesis of several identified
      allelochemicals, providing the potential to improve allelopathy by molecular
      breeding. The dynamics of crop allelopathy, inducible processes and plant
      signalling is gaining growing attention; however, future research should also
      consider allelochemical release mechanisms, persistence, selectivity and modes of
      action, as well as consequences of improved crop allelopathy on plant physiology,
      the environment and management strategies. Creation of weed-suppressive cultivars
      with improved allelopathic interference is still a challenge, but traditional
      breeding or biotechnology should pave the way.

PMID- 17195967
TI  - University of Rhode Island Change Assessment-Trauma: preliminary psychometric
      properties in an alcohol-dependent PTSD sample.
AB  - The co-occurrence of posttraumatic stress disorder with substance use disorders
      (PTSD-SUD) is common and is associated with poorer treatment outcomes. Attrition
      represents an ongoing, but poorly understood challenge in PTSD-SUD treatment
      research. The current study examined the initial psychometric properties of the
      University of Rhode Island Change Assessment-Trauma (URICA-T), a scale designed
      to assess attitudes and behaviors related to addressing trauma issues, in a
      sample of 42 individuals meeting diagnostic criteria for PTSD and alcohol
      dependence. Results suggest that the URICA-T may have acceptable psychometric
      properties as a continuous measure of motivational readiness in a PTSD-SUD
      sample. Preliminary data also suggests higher URICA-T scores are associated with
      retention of alcohol dependent-PTSD participants in a study utilizing trauma
      focused exposure.

PMID- 17195968
TI  - Posttraumatic stress after a motor vehicle accident: a six-month follow-up study
      utilizing latent growth modeling.
AB  - Features of posttraumatic stress disorder (PTSD) for 596 survivors of motor
      vehicle accidents were examined by self-report measures at 1 week, 1 month, 3
      months, and 6 months after the motor vehicle accident (MVA). Latent growth
      modeling was utilized to study the trend and predictors of the level of distress.
      Results indicated that 5-20% of the participants reported to have a significant
      level of posttraumatic stress in one, two, or three of the PTSD symptom clusters
      within the period studied. Survivors with significant acute stress 1 week after
      the MVA had a higher risk for developing chronic posttraumatic stress. Although
      the severity of intrusive and hyperarousal symptoms decreased over time, the
      severity of avoidance symptoms remained unchanged. Factors predicting the course
      of PTSD after an MVA are identified.

PMID- 17195969
TI  - Traumatic events and alcohol use disorders among American Indian adolescents and
      young adults.
AB  - This study examined the relationship between severe traumatic events and alcohol
      use disorders in American Indian adolescents and young adults. Interviews of 432
      adolescents and young adults who were enrolled tribal members living on or near
      two closely related American Indian reservations were used. Results indicated
      that severe trauma increased the odds of alcohol use disorders (p <.001), with
      the number of traumas having a dose-dependent effect. The authors conclude that
      trauma is associated with alcohol use disorders in this population. This study's
      findings yield important insights into the risks in American Indian adolescents
      and young adults that may result from early trauma, as well as implications for
      the timing and possible settings for intervention.

PMID- 17195970
TI  - Verbal and physical aggression in World War II former prisoners of war: role of
      posttraumatic stress disorder and depression.
AB  - This study examined the relationship among posttraumatic stress disorder (PTSD),
      depression, and intimate partner relationship aggression in a community sample of
      World War II (WWII) male military former prisoners of war (POWs). Sixty percent
      of these POWs reported verbal aggression in their marriages, and 12% endorsed
      physical aggression. Both verbal and physical aggression were significantly
      correlated to the severity of captivity trauma and to PTSD symptoms.
      Posttraumatic stress disorder symptoms significantly mediated the relationship
      between severity of trauma and both verbal and physical aggression. Depression
      was a significant moderator of the relationship between PTSD and both physical
      and verbal aggression. Theoretical and clinical implications are suggested.

PMID- 17195971
TI  - The impact of resource loss and traumatic growth on probable PTSD and depression
      following terrorist attacks.
AB  - The authors interviewed by phone 2,752 randomly selected individuals in New York
      City within 6 to 9 months after the attacks of September 11, 2001 on the World
      Trade Center, and 1,939 of these were reinterviewed at a 12- to 16-month follow
      up. It was hypothesized that resource loss would significantly predict probable
      posttraumatic stress disorder (PTSD) and probable depression since September 11,
      and that resource loss's impact would be independent of previously identified
      predictors relating to individuals' demographic characteristics, history of
      stressful event exposure, prior trauma history, peritraumatic experience, and
      social support. Second, it was predicted that reported traumatic growth would be
      related to greater, not lesser, psychological distress. The authors' findings
      supported their hypotheses for resource loss, but traumatic growth was unrelated
      to psychological outcomes when other predictors were controlled.

PMID- 17195972
TI  - Influence of cultivation conditions on mechanical and morphological properties of
      bacterial cellulose tubes.
AB  - Bacterial cellulose (BC) was deposited in tubular form by fermenting Acetobacter
      xylinum on top of silicone tubes as an oxygenated support and by blowing
      different concentrations of oxygen, that is, 21% (air), 35%, 50%, and 100%.
      Mechanical properties such as burst pressure and tensile properties were
      evaluated for all tubes. The burst pressure of the tubes increased with an
      increase in oxygen ratio and reached a top value of 880 mmHg at 100% oxygen. The
      Young's modulus was approximately 5 MPa for all tubes, irrespective of the oxygen
      ratio. The elongation to break decreased from 30% to 10-20% when the oxygen ratio
      was increased. The morphology of the tubes was characterized by Scanning Electron
      Microscopy (SEM). All tubes had an even inner side and a more porous outer side.
      The cross section indicated that the tubes are composed of layers and that the
      amount of layers and the yield of cellulose increased with an increase in oxygen
      ratio. We propose that an internal vessel wall with high density is required for
      the tube to sustain a certain pressure. An increase in wall thickness by an
      increase in oxygen ratio might explain the increasing burst pressure with
      increasing oxygen ratio. The fermentation method used renders it possible to
      produce branched tubes, tubes with unlimited length and inner diameters.
      Endothelial cells (ECs) were grown onto the lumen of the tubes. The cells formed
      a confluent layer after 7 days. The tubes potential as a vascular graft is
      currently under investigation in a large animal model at the Centre of Vascular
      Engineering, Sahlgrenska University

PMID- 17195973
TI  - Correlates of posttraumatic growth in survivors of intimate partner violence.
AB  - The negative consequences of intimate partner violence are well documented. This
      study investigated the possibility that some survivors of intimate partner
      violence may also experience posttraumatic growth because of their struggle with
      this highly stressful circumstance. In addition, the relationships between
      posttraumatic growth and relationship status, type of abuse, depression, and
      availability of models of posttraumatic growth were examined. Most women reported
      posttraumatic growth. Overall abuse experienced and depression were unrelated to
      posttraumatic growth, but abuse was related to one domain of growth. Contact with
      a model of posttraumatic growth and having left an abusive relationship were both
      positively related to posttraumatic growth.

PMID- 17195974
TI  - Special section: innovations in trauma research methods, 2005.

PMID- 17195976
TI  - Latent difference score approach to longitudinal trauma research.
AB  - In this article, the authors introduce a latent difference score (LDS) approach
      to analyzing longitudinal data in trauma research. The LDS approach accounts for
      internal sources of change in an outcome variable, including the influence of
      prior status on subsequent levels of that variable and the tendency for
      individuals to experience natural change (e.g., a natural decrease in
      posttraumatic stress disorder [PTSD] symptoms over time). Under traditional model
      assumptions, the LDSs are maximally reliable and therefore less likely to
      introduce biases into model testing. The authors illustrate the method using a
      sample of children who experienced significant burns or other injuries to examine
      potential influences (i.e., age of child-adolescent at time of trauma and ongoing
      family strains) on PTSD symptom severity over time.

PMID- 17195975
TI  - Maximizing follow-up in longitudinal studies of traumatized populations.
AB  - Although longitudinal research is essential in understanding the nature and
      course of posttraumatic mental health problems, high rates of attrition often
      threaten the internal validity of such studies and make results hard to
      interpret. C. K. Scott (2004) developed an approach to minimizing attrition in
      longitudinal studies that consistently yielded retention rates in excess of 90%
      through to 2-year follow-up. In this article, the authors discuss the interface
      between trauma exposure and participation in longitudinal research, before
      describing in detail a model to address those effects. The effectiveness of the
      model is examined with reference to traumatic stress in a large community sample
      (N = 887) with eight waves of data over 2 years.

PMID- 17195977
TI  - A guide to economic evaluation: methods for cost-effectiveness analysis of person
      level data.
AB  - The authors introduce economic evaluation with particular attention to cost
      effectiveness analysis. They begin by establishing why health care decisions
      should be guided by economics. They then explore different types of economic
      evaluations. To illustrate how to conduct and evaluate a cost-effectiveness
      analysis, a hypothetical study about the treatment of posttraumatic stress
      disorder with psychotherapy versus pharmacotherapy is considered. The authors
      conclude with recommendations for increasing the strength and relevance of
      economic evaluations.

PMID- 17195978
TI  - Changes in coping strategies, relationship to the perpetrator, and posttraumatic
      distress in female crime victims.
AB  - This study examined the relationship between changes in coping and posttraumatic
      stress disorder (PTSD) symptomatology among recent female rape and physical
      assault victims as a function of assault type and perpetrator status.
      Participants were assessed within 1 month after trauma and again at 3 months
      after trauma. Results indicate that changes in coping strategies over time are
      associated with the severity of the PTSD symptoms. Assault type was not a
      significant factor in the association between changes in coping and PTSD, but
      perpetrator status was. Victims with known perpetrators, who coped more by social
      withdrawal, had more severe PTSD symptoms over time. The importance of examining
      the dynamic nature of coping in the development of PTSD is discussed.

PMID- 17195979
TI  - Coping, symptoms, and functioning outcomes of patients with posttraumatic stress
      disorder.
AB  - This study examines the association between approach coping and better
      functioning outcomes and the reciprocal relationships between coping and
      posttraumatic stress disorder (PTSD) symptoms in patients diagnosed with PTSD.
      Posttraumatic stress disorder patients receiving services in five VA health care
      systems were randomly selected and surveyed at baseline and followed 10 months
      later. Analyses of longitudinal data using structural equation modeling
      techniques showed that more approach coping predicted better family and social
      functioning. Cognitive avoidance coping predicted more PTSD symptoms, and more
      PTSD symptoms predicted more approach coping and more behavioral avoidance
      coping. Approach coping may enable patients with chronic PTSD to establish and
      maintain better relationships with family and friends, despite continuing PTSD.

PMID- 17195980
TI  - Posttraumatic stress disorder in female veterans with military and civilian
      sexual trauma.
AB  - This study examines relationships among military sexual trauma (MST), nonmilitary
      sexual trauma, and posttraumatic stress disorder (PTSD). A sample of 196 female
      veterans was assessed for trauma occurring before, during, and after military
      service, and for current PTSD. The prevalence of MST was higher than that of
      premilitary and postmilitary sexual trauma. Premilitary trauma did not
      significantly increase the odds of experiencing MST, but did increase the odds of
      experiencing postmilitary sexual trauma. Logistic regression analyses revealed
      MST was more strongly associated with PTSD than was premilitary or postmilitary
      trauma. Women with MST had the greatest increased odds of developing PTSD.
      Understanding risk factors for and taking steps to prevent MST may reduce cases
      of PTSD in female veterans.

PMID- 17195981
TI  - Cumulative interpersonal traumas and social support as risk and resiliency
      factors in predicting PTSD and depression among inner-city women.
AB  - This study represents one of the largest examinations of how child abuse, adult
      rape, and social support impact inner-city women (N = 777). Using retrospective
      self-report, the effects of interpersonal trauma were shown to be cumulative such
      that women who experienced either child abuse or adult rape were 6 times more
      likely to have probable posttraumatic stress disorder (PTSD), whereas women who
      experienced both child abuse and rape were 17 times more likely to have probable
      PTSD. High social support predicted lower PTSD severity for women who experienced
      both child abuse and adult rape, but not for women who reported one or none of
      these traumas. Results suggest that social support, when left intact, might
      buffer the cumulative impact of child and adult interpersonal traumas.

PMID- 17195982
TI  - Posttraumatic stress disorder and treatment seeking in a nationally
      representative Canadian military sample.
AB  - This study aimed to identify predictors of treatment seeking in military members
      with posttraumatic stress disorder (PTSD) using data from the 2002 Canadian
      Community Health Survey-Canadian Forces Supplement (Statistics Canada, 2003). To
      identify predictors, two complementary analyses (binary logistic regression and
      recursive partitioning of independent variables) were conducted in military
      members with PTSD (N = 509). Results indicate that trauma-related (index
      traumatic event type, cumulative trauma exposure), demographic (marital status),
      enabling (income), and need (PTSD interference) factors predict treatment seeking
      in military members with PTSD, and that treatment seekers and nontreatment
      seekers are both comprised of distinct subgroups. Interventions aimed at
      increasing treatment-seeking behaviors should be tailored to the specific needs
      of various subgroups of nontreatment seekers.

PMID- 17195983
TI  - Childhood abuse and intake severity in alcohol disorder patients.
AB  - In a sample of 336 patients with an alcohol use disorder, this study examined,
      whether patients with histories of childhood sexual abuse (CSA) and childhood
      physical abuse (CPA) compared to those without such histories have a greater
      severity of alcohol and other clinical difficulties. Whether lifetime
      posttraumatic stress disorder (PTSD) mediates the relationship between childhood
      abuse and clinical outcomes was explored. Results were that CSA was associated
      with earlier age of onset for alcohol disorder, greater Axis I comorbidity as
      defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (DSM-IV; American Psychiatric Association, 1994), more social and
      psychiatric problems, but lower drinking frequency. Childhood physical abuse was
      related to greater drinking consequences, social and psychiatric dysfunction, and
      Axis I comorbidity, but also lower drinking frequency. Posttraumatic stress
      disorder partially mediated the effect of both CSA and CPA on severity of
      psychiatric problems.

PMID- 17195985
TI  - The association between childhood abuse, PTSD, and the occurrence of adult health
      problems: moderation via current life stress.
AB  - The association between childhood abuse, current life stressors, and the
      occurrence of adult medical problems was investigated in the National Comorbidity
      Survey. It was found that after controlling for a number of covariates, current
      life stressors moderated the relationship between abuse history and medical
      problems such that health problems were greater for individuals who had been
      abused in the presence of current stressors. The findings suggest that a history
      of childhood abuse, even without the presence of posttraumatic stress disorder
      (PTSD), can influence the occurrence of poor health if current life stressors are
      present. Future directions and implications are discussed.

PMID- 17195984
TI  - Is mixed-handedness a marker of treatment response in posttraumatic stress
      disorder?: a pilot study.
AB  - Recent studies suggest that mixed-handedness is a risk factor for posttraumatic
      stress disorder (PTSD). This study examined whether mixed-handed veterans with
      combat-related PTSD respond more poorly to psychosocial treatment. Consistency of
      hand preference was assessed in 150 Vietnam combat veterans with PTSD using the
      Edinburgh Handedness Inventory (R. C. Oldfield, 1971). Growth modeling analyses
      using Mplus (L. K. Muthen & B. Muthen, 2002) identified that PTSD veterans with
      mixed-handedness reported significantly less treatment improvement on the PTSD
      Checklist (F. W. Weathers, B. T. Litz, D. S. Herman, J. A. Huska, & T. M. Keane,
      1993) than did veterans with consistent handedness. These data suggest that mixed
      handedness is associated with poorer PTSD treatment response. Several possible
      explanations for this finding are discussed.

PMID- 17195986
TI  - Positive and negative adjustment and social support of sexual assault survivors.
AB  - The roles of positive (i.e., growth) and negative (i.e., posttraumatic stress
      symptoms and general symptomatology) adjustment following adult sexual assault
      experience(s) were examined using a standardized definition of abuse. These
      reactions were explored in association with positive and negative support from
      formal and informal providers. Finally, using standardized measures, the
      collective impact of positive and negative support, formal and informal support
      were investigated in predicting positive and negative psychological adjustment.
      Both forms of informal support were found to be associated with positive
      outcomes. Only negative informal support was associated with posttraumatic stress
      symptoms. First responders should consider whether support resources are
      appropriate to victims' needs.

PMID- 17195987
TI  - El Salvador earthquakes: relationships among acute stress disorder symptoms,
      depression, traumatic event exposure, and resource loss.
AB  - Four and seven weeks after powerful earthquakes in El Salvador, the authors
      examined the relationships among demographics, traumatic event exposure, social
      support, resource loss, acute stress disorder (ASD) symptoms, depression, and
      posttraumatic growth. Participants were 253 college students (Study 1) and 83
      people in the community (Study 2). In Study 1, female gender, traumatic event
      exposure, low social support, and loss of personal characteristic, condition, and
      energy resources contributed to ASD symptoms and depression. In Study 2, damage
      to home and loss of personal characteristic and object resources contributed to
      ASD symptoms and depression. Posttraumatic growth was not associated with ASD
      symptoms or depression. Findings support the conservation of resources stress
      theory (Hobfoll, 1998). Resource loss spirals, excessive demands on coping, and
      exposure to multiple disasters are discussed.

PMID- 17195988
TI  - Analysis of oxygen transport in a diffusion-limited model of engineered heart
      tissue.
AB  - Cardiac tissue engineering has made notable progress in recent years with the
      advent of an experimental model based on neonatal cardiomyocytes entrapped in
      collage gels and purified basement membrane extract, known as "engineered heart
      tissues" (EHTs). EHTs are a formidable display of tissue-level contractile
      function and cellular-level differentiation, although they suffer greatly from
      mass transport limitations due to the high density of metabolically active cells
      and the diffusion-limited nature of the hydrogel. In this report, a mathematical
      model was developed to predict oxygen levels inside a one-dimensional, diffusion
      limited model of EHT. These predictions were then compared to values measured in
      corresponding experiments with a hypoxia-sensitive stain (pimonidazole). EHTs
      were cast between two plastic discs, which allowed for mass transfer with the
      culture medium to occur in only the radial direction. EHTs were cultured for up
      to 36 h in the presence of pimonidazole, after which time they were snap-frozen,
      histologically sectioned, and stained for bound pimonidazole. Quantitative image
      analysis was performed to measure the distance from the culture medium at which
      hypoxia first occurs under various conditions. As tested by variation of simple
      design parameters, the trends in oxygen profiles predicted by the model are in
      reasonable agreement with those obtained experimentally, although a number of
      ambiguities related to the specific model parameters led to a general
      overprediction of oxygen concentrations. Based on the sensitivity analysis in the
      present study, it is concluded that diffusion-reaction models may offer
      relatively precise predictions of oxygen concentrations in diffusion-limited
      tissue constructs.

PMID- 17195989
TI  - Sonographic diagnosis of acute injuries of the ulnar collateral ligament of the
      metacarpophalangeal joint of the thumb.
AB  - PURPOSE: To evaluate the significance of the ultrasonographic appearance of the
      aponeurosis for deciding the best treatment for ulnar collateral ligament (UCL)
      injuries of the thumb metacarpophalangeal joint. METHODS: Fourteen patients (11
      men, 3 women; mean age, 41 years; range, 15-66 years) who had an acute UCL tear
      were included. All patients were examined by ultrasonography (US) with a 7.5-MHz
      transducer and subsequently underwent surgery. The ultrasonographic findings were
      compared to the intraoperative findings. RESULTS: UCL injuries were classified
      into two types by US according to the appearance of aponeurosis and its spatial
      relationship with the UCL: the intra-aponeurosis type (5 patients) and the extra
      aponeurosis type (9 patients). In the 5 patients with intra-aponeurosis,
      ultrasonographic findings were well consistent with intraoperative findings. In
      contrast, extra-aponeurosis cases contained two different pathologies: of the 9
      patients, 7 had so-called 'Stener lesions', one showed folding of a ruptured
      capsule, and one showed a ruptured aponeurosis. CONCLUSIONS: Because US is highly
      reliable in differentiating intra-aponeurosis from extra-aponeurosis types of
      injuries, the aponeurosis is a more reliable reference than Stener lesion for
      treatment decision by US.

PMID- 17195990
TI  - The effects of environmental factors on the prevalence of Helicobacter pylori
      infection in inhabitants of Lublin Province.
AB  - The aim of the study was to analyse the prevalence of H. pylori infection in
      adult inhabitants of Lublin Province. The effects of living conditions and
      lifestyle on the infection frequency were evaluated. The study included 585
      adults randomly chosen for the epidemiological analysis of H. pylori infection in
      the Lublin region within the project commissioned by the Ministry of Health (PCZ
      08-09) and State Committee for Scientific Research (C007/P05/2000). The study was
      based on a personal questionnaire and determinations of anti/Hp antibodies in IgG
      class using the ELISA method. High titres of anti/Hp antibodies (> 24 IU/ml) were
      demonstrated in 78.5 % of the subjects. In Lublin Province the infected
      individuals constitute 72 % of inhabitants, in the big towns--74 % and in small
      towns--95 %. According to the place of birth: among those born in the country 87
      % are infected, compared to 78.4 % in the small towns and 64 % in the big towns,
      respectively. Positive test results were observed in 79 % of farmers, 78 % of
      manual workers and 75 % of mental workers. The percentage of the affected
      neglecting basic hygienic rules exceeded 90 %. With increased frequency of
      hygienic measures the number of the H. pylori infected individuals decreased to
      65 %. The prevalence of H. pylori infection among the inhabitants of the Lublin
      region is lower than that found in town inhabitants. Lublin Province shows the
      lowest level of H. pylori infection in Poland. The H. pylori infection is
      strongly affected by the lack of basic rules of personal hygiene and improper
      diet.

PMID- 17195991
TI  - Fungi recovered from Slovakian poultry feed mixtures and their toxinogenity.
AB  - To contribute towards the knowledge of microbiology of feeds, more than 100
      samples of poultry feed mixtures from Slovakia were mycologically investigated in
      terms of the overall fungal diversity and toxicological potential of isolated
      fungi. The study revealed that out of 22 genera recovered, Penicillium was the
      most frequent and diverse genus, followed by Aspergillus and Mucor being found in
      89 % (34 spp.), 69 % (11 spp.) and 50 % (4 spp.), respectively. The most
      frequently encountered taxa were Fusarium proliferatum, followed by Penicillium
      aurantiogriseum, Mucor racemosus, Penicillium crustosum and Aspergillus flavus .
      In addition, the following genera were recorded (in descending order) Rhizopus
      (44 %, 3 spp.), Eurotium (42 %, 5 spp.), Fusarium (42 %, 3 spp.), Cladosporium
      (31 %, 1 sp.), Alternaria (22 %, 3 spp.), Absidia (16 %, 3 spp.), Acremonium (12
      %, 2 spp.), Scopulariopsis (10 %, 2 spp.), Paecilomyces (4 %, 1 sp.), Ulocladium
      (3 %, 1 sp.), Trichoderma (2 %, 1 sp.), Zygorrhynchus (2 %, 1 sp.), and finally
      Emericella, Epicoccum, Geosmithia, Monascus, Stachybotrys, Syncephalastrum and
      Wardomyces , all were encountered in 1 % of the samples being represented by a
      single species. The mean value counts of total fungi ranged from 1 x 10 (3) to
      200 x 10(5) cfu/g. Outcomes from mycotoxin screening within the appropriate
      potentially toxinogenic species showed a number of mycotoxin producers, namely
      those forming aflatoxin B (1) (n=3), citrinin (17), cyclopiazonic acid (76),
      fumonisin B(1) (86), griseofulvin (42), moniliformin (18), ochratoxin A (5),
      patulin (56), penitrem A (30) and sterigmatocystin (10).

PMID- 17195992
TI  - A three-year aeropalynological study in Estepona (southern Spain).
AB  - An aeropalynological study was carried out in the atmosphere of Estepona, a very
      popular tourist resort situated in the "Costa del Sol", (southern Spain) based on
      the data obtained during a three year air-monitoring programme (March 1995 to
      March 1998) using a volumetric pollen trap. The 34 taxa that reached a 10-day
      mean air pollen concentration equal to or greater than 1 grain of pollen/m(3) of
      air are reflected in the calendar. The first 10 taxa, in order of abundance,
      were: Cupressaceae, Olea europaea, Quercus, Poaceae, Urticaceae, Plantago, Pinus,
      Chenopodiaceae-Amaranthaceae, Ericaceae and Castanea, the first 3 of which
      accounted for approximately 56 % of the annual total pollen count. The greatest
      diversity of pollen type occurred during spring, while the highest pollen
      concentrations were reached from February-June, when approximately more than 80 %
      of the annual total pollen was registered. The lowest concentrations were
      obtaining during January, August and September. The annual quantity of pollen
      collected, the intensity and the dates on which the maximum peaks were recorded
      differed for the 3 years studied, which can be explained by reference to various
      meteorological parameters, especially rainfall and temperature. The pollen
      calendar spectrum is typically Mediterranean and similar to those of nearby
      localities, in which many pollen types are represented and the long tails
      indicating long flowering periods.

PMID- 17195994
TI  - Measurement of personal exposure to outdoor aeromycota in northern New South
      Wales, Australia.
AB  - Aerobiological sampling traditionally uses a volumetric spore trap located in a
      fixed position to estimate personal exposure to airborne fungi. In this study,
      the number and identity of fungi inhaled by human subjects (n=34), wearing Intra
      nasal air samplers (INASs), was measured over 2-hour periods in an outdoor
      community setting, and compared to fungal counts made with a Burkard spore trap
      and Institute of Occupational Medicine personal filter air samplers (IOMs). All
      sampling devices were in close proximity and located in an outdoor environment in
      Casino, northern New South Wales, Australia. Using INASs, the most prevalent
      fungi inhaled belonged to soil or vegetation borne spores of Alternaria,
      Arthrinium, Bipolaris, Cladosporium, Curvularia, Epicoccum, Exserohilum,
      Fusarium, Pithomyces, Spegazzinia and Tetraploa species, Xylariaceae ascospores,
      in addition to hyphal fragments. These results showed that inhaled fungal
      exposure in most people varied in a 2-fold range with 10-fold outliers. In
      addition, the INASs and personal air filters agreed more with each other than
      with Burkard spore trap counts (r=0.74, p < 0.0001). These findings further
      support a new paradigm of personal fungal exposure, which implicates the
      inhalation of a spectrum of fungi more closely associated with soil or vegetation
      borne mycoflora and hyphal fragments than what is collected by stationary spore
      traps in the same geographic region.

PMID- 17195993
TI  - Quercus pollen season dynamics in the Iberian peninsula: response to
      meteorological parameters and possible consequences of climate change.
AB  - The main characteristics of the Quercus pollination season were studied in 14
      different localities of the Iberian Peninsula from 1992-2004. Results show that
      Quercus flowering season has tended to start earlier in recent years, probably
      due to the increased temperatures in the pre-flowering period, detected at study
      sites over the second half of the 20th century. A Growing Degree Days forecasting
      model was used, together with future meteorological data forecast using the
      Regional Climate Model developed by the Hadley Meteorological Centre, in order to
      determine the expected advance in the start of Quercus pollination in future
      years. At each study site, airborne pollen curves presented a similar pattern in
      all study years, with different peaks over the season attributable in many cases
      to the presence of several species. High pollen concentrations were recorded,
      particularly at Mediterranean sites. This study also proposes forecasting models
      to predict both daily pollen values and annual pollen emission. All models were
      externally validated using data for 2001 and 2004, with acceptable results.
      Finally, the impact of the highly-likely climate change on Iberian Quercus pollen
      concentration values was studied by applying RCM meteorological data for
      different future years, 2025, 2050, 2075 and 2099. Results indicate that under a
      doubled CO(2) scenario at the end of the 21st century Quercus pollination season
      could start on average one month earlier and airborne pollen concentrations will
      increase by 50 % with respect to current levels, with higher values in
      Mediterranean inland areas.

PMID- 17195995
TI  - Climate and environmental factors influencing Echinococcus multilocularis
      occurrence in the Slovak Republic.
AB  - During the period of 2000-2004, 3,096 red foxes from the whole territory of the
      Slovak Republic were sampled and examined parasitologically for infections with
      Echinococcus multilocularis, causative agent of serious alveolar echinococcosis
      in humans. Relations between prevalence of the parasite in individual regions of
      Slovakia and some environmental factors were weighted. During the study period,
      great differences of prevalence and infection intensity were found on a regional
      level and significant between-year fluctuation of both parameters was observed.
      High-endemic foci with an estimated prevalence of more than 30 % were detected in
      the northern and central part of the country. Climatic conditions, including low
      mean annual air temperature, high mean annual rainfall and the high humidity of
      the soil, showed to be important for E. multilocularis distribution. Significant
      correlation was calculated between prevalence of the tapeworm, mean annual
      precipitation values, and population density of small mammals.

PMID- 17195996
TI  - Effect of meteorological factors on Betula, Fraxinus and Quercus pollen
      concentrations in the atmosphere of Lublin and Szczecin, Poland.
AB  - The aim of the study was to compare the concentration of 3 allergenic taxa pollen
      (ash, birch and oak) in the cities of Lublin (eastern Poland) and Szczecin
      (western Poland) during the years 2004 and 2005 and examine correlations between
      weather factors and pollen concentration. The meteorological parameters analysed
      were maximum and mean air temperature, relative humidity, amount of precipitation
      and wind speed. Measurements were performed by the volumetric method (Lanzoni
      2000 pollen sampler). Pollen seasons were defined as the period in which 95 % of
      the total catch occurred. The pollen seasons of the studied taxa started earlier
      in Szczecin than in Lublin. In both cities much higher Betula pollen
      concentration and slightly higher Fraxinus pollen concentration were recorded in
      2004 compared to 2005. But for Quercus, higher concentrations were recorded in
      Lublin and in Szczecin in 2005. Annual totals and maximum daily pollen grain
      concentrations of the tree taxa in question were higher in Lublin than in
      Szczecin. In 2005, maximum Betula and Fraxinus pollen concentrations occurred in
      each of the cities at the same time: in Lublin on 18 April, in Szczecin on 16
      April. Among the meteorological parameters analysed, maximum temperature and
      relative humidity belong to the most important factors which affect ash, birch
      and oak pollen concentrations in the air.

PMID- 17195997
TI  - Dust emission rates from food processing.
AB  - A field study was performed to develop emission rates for dust exposure at a food
      processing facility. Eight 2-hour periods were monitored over 2 days. Area total
      suspended particulate samples were collected on 37 mm polyvinyl chloride filters
      with 5 mum pore size according to NIOSH Method 0500. Filters were analyzed
      gravimetrically. Ventilation and production activity data were collected during
      air sampling. Two mass balance models were used to calculate emission rates. The
      first was an experimental mass balance model, with the mass of contaminant
      generated determined by air flow and concentration measurements at room exit and
      entry points. The second treated the work environment as a completely mixed
      space, utilizing ventilation and area concentration measurements. Emission rates
      generated from mass balance models ranged from 2.09-542 mg/min for the various
      processing operations and food products. Process emission rates with production
      activity data allow estimation of dust exposure in similar facilities, and help
      direct development of exposure control strategies.

PMID- 17195998
TI  - Pulmonary cytotoxicity of secondary metabolites of Stachybotrys chartarum
      (Ehrenb.) Hughes.
AB  - Damp dwellings represent suitable conditions for extended indoor moulds. A
      cellulolytic micromycete Stachybotrys chartarum (Ehrenb.) Hughes is considered to
      be a tertiary colonizer of surfaces in affected buildings. Known adverse health
      effects of S. chartarum result from its toxins--trichothecenes or atranones, as
      well as spirolactams. Mechanism of their potential pathological effects on the
      respiratory tract has not yet been sufficiently clarified. The cytotoxic effects
      of complex chloroform-extractable endo- (in biomass) and exometabolites (in
      cultivation medium) of an indoor S. chartarum isolate of an atranone chemotype,
      grown on a liquid medium with yeast extract and sucrose at 25 degrees C for 14 d,
      on lung tissue were evaluated in the 3-day experiment. For the purpose, 4 mg of
      toxicants were intratracheally instilled in 200 g Wistar male rats. A
      trichothecene mycotoxin diacetoxyscirpenol was used as the positive control.
      Bronchoalveolar lavage (BAL) parameters--viability and phagocytic activity of
      alveolar macrophages (AM), activity of lactate dehydrogenase, acid phosphatase
      and cathepsin D in cell-free BAL fluid (BALF), as well as in BAL cells, were
      measured. Acute exposure to the metabolites caused statistically significant
      changes, indicating lung tissue injury in the experimental animals. Decreased AM
      viability and increased activity of lysosomal enzyme cathepsin D in BAL cells
      after fungal exometabolite exposure were the most impressive. As toxic principles
      were found predominantly in the growth medium, toxins were more likely
      responsible for lung cell damage than e.g. fungal cell wall components. S.
      chartarum toxic metabolites can contribute to the ill health of occupants of
      mouldy building after inhalation of contaminated aerosol.

PMID- 17195999
TI  - Airborne grass and ragweed pollen in the southern Panonnian Valley--consideration
      of rural and urban environment.
AB  - The aims of this study were to describe and compare the characteristics of grass
      and ragweed airborne pollen in rural and urban areas in the southern Panonnian
      Valley. Airborne pollen data were collected by using Hirst type volumetric
      samplers simultaneously in rural and urban localities. If rural and urban
      environment are considered, both grass and ragweed daily pollen concentrations
      showed a significant degree of association. Observed parameters (pollen index,
      maximum daily concentration, number of days during which the pollen is recorded
      in the air and start day of main pollen season), showed year-to-year variations
      for both grass and ragweed aeropollen. Average values of these parameters were
      higher in the rural environment, but the difference was statistically significant
      only for grass pollen index. Such a low difference indicates the possibility for
      conducting dose response clinical trials based on data obtained from one sampling
      station. The least year-to-year variations as well as the least difference
      between rural and urban environment, have been observed in the case of start date
      of the MPS. Such a situation suggests the possibility for using data obtained in
      one type of environment for the development of long-term forecast models for an
      entire region.

PMID- 17196000
TI  - Impact of agricultural practices on microbiology of hay, silage and flour on
      Finnish and French farms.
AB  - Exposure to microorganisms in farm environments may cause respiratory disorders,
      e.g. asthma, organic dust toxic syndrome and allergic alveolitis. By reducing
      microbiological deterioration of organic materials, some agricultural practices
      have a protective effect. Microbiological analyses were carried out on hay,
      silage and flour samples (n=107) from farms in Finland and France (n=23) that use
      different methods of haymaking. High concentrations of Absidia corymbifera were
      found in approximately 35 % of French hay samples and only 10 % of Finnish hay
      samples. Concentrations of Eurotium spp. were found in 20 % of hay samples from
      both regions. High concentrations of Wallemia sebi typified Finnish hay (38 %)
      more than French hay (8 %). Rhodotorula yeast was frequently and abundantly found
      in Finland, but never in France. The method used to make hay appeared to be the
      main factor affecting the microbiology of the hay. A. corymbifera and Eurotium
      spp. concentrations were smaller in low-density square bales than in others. In
      conclusion, our results emphasize the importance of good agricultural practice in
      the microbiological quality of fodder.

PMID- 17196001
TI  - Microbial contamination in dental unit waterlines: comparison between Er:YAG
      laser and turbine lines.
AB  - The investigation was carried out by evaluating the microbiological
      characteristics of the water before and after treatment with Er:YAG laser and
      turbine. The study was carried out in 2 dental surgeries. In both cases the laser
      and dental units were served by two independent circuits, fed by the same potable
      tap water. Samples were taken from the water supplying and the water leaving the
      turbine and laser before and after treatment on the same patient. Total
      heterotrophic plate count was measured at 36 degrees C and at 22 degrees C, and
      the presence of Staphylococcus species and non-fermenting Gram negative bacteria
      was investigated. Bacterial contamination was found within the circuit,
      especially in the laser device. Pseudomonas aeruginosa was detected in only 1
      sample of supply water, in 11.1 % and in 19.4 % of the samples from the turbine
      and the laser respectively. No evidence of Staphylococcus aureus was found. The
      contamination of supply water was low, whereas that of the water leaving the
      handpieces of the 2 devices was high, especially in the laser. Attention should
      be paid to the control of the water leaving laser devices, given the increasingly
      wide use of such instruments in dental treatment exposed to risk of infection.

PMID- 17196002
TI  - Change in the quality of diet during pregnancy in comparison with WHO and EU
      recommendations--environmental and sociodemographic conditions.
AB  - The organism of a pregnant woman constitutes the environment for the developing
      embryo. The outside world influencing the mother's organism affects not only her
      health but also her unborn baby's health. The aim of the work is to analyze the
      qualitative changes in pregnant women's diet and to specify the sociodemographic
      and environmental conditions determining the quality of the diet. The research
      was carried out among 150 pregnant women who came to randomly chosen antenatal
      clinics in Lublin. The tool used for research was a personally designed
      questionnaire. The average consumption of particular groups of products was
      counted. Pregnant women not only increased the amount of food they consumed but
      they also changed the proportions. Despite the fact that the consumption of diary
      products was still too much, their role significantly decreased (2.40). Women
      also cut down on fruit in comparison with other products (2.76). However, the
      amounts of meat (1.30), vegetables (4.26) and crop products (4.29) rose.
      Moreover, place of living impacted on the frequency of the consumption of
      vegetables and education--of diary products.

PMID- 17196003
TI  - Application of ozone for reduction of mycological infection in wheat grain.
AB  - In 2004-2005 means were sought to clean grain from microbiological contamination
      during transportation and storage. For this purpose, grains with a moisture
      content of 23.2 % of the "Tauras" variety were selected and ventilated daily for
      8 hours until grain wetness was reduced to 14.0 %. The effect of ventilation
      duration and ozone impact was evaluated according to the changes in grain
      contamination with micromycetes propagules (cfu x g (-1)), and alternation of
      micromycetes species on the grain surface. At drying grains by active ventilation
      with an ozone--air mixture, at O (3) concentration of 700 ppb, the drying period
      was reduced by about 20 %, and mycological contamination depends on initial grain
      moisture content (w): when w=15.2 %, contamination was reduced by up to 2.2
      times, and when w=22.0 %--up to 3 times. At the same time, the composition of
      micromycetes species on the grain surface changed significantly: in non
      ventilated grain there were detected micromycetes of 26 species, and in
      ventilated grain--of 11 species. Efficient ozone impact was established only when
      the mound of wet (w>18.0 %) grains was exposed to ozone.

PMID- 17196004
TI  - Abundance of wild rodents, ticks and environmental risk of Lyme borreliosis: a
      longitudinal study in an area of Mazury Lakes district of Poland.
AB  - The results of a longitudinal epidemiological survey in two contrasting habitats
      in an area of the Mazury Lakes district of Poland indicate that both host and
      vector (Ixodes ricinus) densities, may be the most important risk factors for the
      tick-transmitted spirochetes of Borrelia burgdirferi s.l. However, the results
      also highlight that even related host species, such as the wild rodents Apodemus
      flavicollis and Clethrionomys glareolus that share the same habitat, can show
      quite different dynamics of tick infestation. We provide evidence that the
      woodland populations of A. flavicollis and C. glareolus are more frequently
      infested with larvae than nymphs, and more frequently with both stages than M.
      arvalis in the neighbouring open fallow lands. The prevalence of infestation with
      larvae varied from 92 % for A. flavicollis, and 76 % for C. glareolus to 37 % for
      M. arvalis. Other factors, such as population age structure and sex, were also
      shown to impact on tick densities on hosts at particular times of the year and
      hence on the zoonotic risk. Moreover, particular species of rodents from
      different habitats, A. flavicollis (woodlands) and Microtus arvalis (fallow
      lands) carry infected immature I. ricinus ticks more frequently than C. glareolus
      voles (woodlands). Thus, the relative contribution of each species to the
      cumulative reservoir competence differs among species living in the woodland
      habitats and in relation to voles living in the fallow lands. It follows,
      therefore, that any factor which reduces the relative density of A. flavicollis
      in comparison to other hosts in the wild rodent community, will reduce also the
      risk of human exposure to Lyme borreliosis spirochetes.

PMID- 17196005
TI  - Prevalence of Borrelia burgdorferi genospecies in Ixodes ricinus ticks from
      Lublin region (eastern Poland).
AB  - The objective of the study was to determine the prevalence rate of 3 Borrelia
      burgdorferi genospecies in Ixodes ricinus ticks collected from wooded areas of
      the Lublin region (eastern Poland). A group of 1,813 I. ricinus ticks from 6
      districts were examined for the presence of Borrelia burgdorferi sensu lato
      (B.b.s.l.) by polymerase chain reaction (PCR). Another group of 438 I. ricinus
      ticks collected from 4 districts were examined for the presence of B.b.s.l. by
      culture on BSKH liquid medium confirmed by PCR, and for the presence of Borrelia
      spp. by dark field microscopy (DFM). Borrelia burgdorferi genospecies (Borrelia
      burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii) were determined
      by nested-PCR in 113 ticks lysates showing presence of B.b.s.l. (in PCR or in
      culture and PCR). 5.4 % of I. ricinus ticks examined by PCR showed the presence
      of B.b.s.l. DNA. The infection rate was highest in females (12.1 %), lower in
      males (6.0 %) and the lowest in nymphs (1.7 %) (p < 0.001). The minimum infection
      rate of I. ricinus ticks with B.b.s.l. determined by culture was 3.4 %, whereas
      the minimum infection rate of ticks with motile spirochetes morphologically
      resembling Borrelia spp., determined by DFM, amounted to 11.2 %. The presence of
      all 3 Borrelia burgdorferi genospecies under investigation was found in ticks
      collected from 5 out of 6 examined districts. In 81.4 % of infected ticks only
      single infection with 1 genospecies was observed, while coinfections with 2 or 3
      genospecies were detected respectively in 16.8 % and 1.8 % of infected ticks.
      Borrelia burgdorferi sensu stricto was the dominant genospecies in all examined
      tick stages and districts, both in single infections and in coinfections, and
      found in a total of 62.8 % of I. ricinus ticks infected with B.b.s.l. Borrelia
      afzelii and Borrelia garinii were less frequent and observed in respectively 39.8
      % and 17.8 % of infected ticks.

PMID- 17196006
TI  - Correlation of tests for detection of Borrelia burgdorferi sensu lato infection
      in patients with diagnosed borreliosis.
AB  - A group of 180 patients with diagnosed Lyme borreliosis were examined for the
      presence of infection with Borrelia burgdorferi sensu lato (B. burgdorferi s.l.)
      by serologic tests with B. burgdorferi s.l. antigens (IgM-ELISA, IgG-ELISA, IgM
      immunoblot, IgG-immunoblot) and by polymerase chain reaction (PCR, nested-PCR)
      for detection of B. burgdorferi s.l. DNA in peripheral blood. A total of 61.7 %,
      53.9 %, 62.2 %, and 59.4 % of the examined patients' sera showed positive or
      borderline results in the serologic tests IgM-ELISA, IgG-ELISA, IgM-immunoblot,
      and IgG immunoblot, respectively. The results of the tests IgM-ELISA and IgM
      immunoblot were significantly correlated (p < 0.001). A higher degree of the
      correlation (p < 0.000001) was found at the comparison of results obtained with
      IgG-ELISA and IgG-immunoblot. The correlation between the positive findings in
      the IgM-ELISA and detection with IgM-immunoblot the diagnostically important B.
      burgdorferi s.l. OspC surface protein was relatively low but statistically
      significant (0.01 < p < 0.05). Much higher correlation was found between the
      positive findings in the IgG-ELISA and detection with IgG-immunoblot other
      diagnostically important B. burgdorferi s.l. antigen, the VlsE protein (p <
      0.000001). The presence of B. burgdorferi s.l. DNA was found by PCR in 20 out 180
      examined blood samples (11.1 %). No correlation was found to exist between the
      PCR results and the results of any of the serologic tests for detection of anti
      B. burgdorferi s.l. antibodies of IgM class. PCR results correlated significantly
      at a relatively low level (0.01 < p < 0.05) with the results of IgG-ELISA, but
      not with the results of IgG-immunoblot with regard to total reactions (0.2 < p <
      0.1). By contrast, a distinctly significant correlation was found between the PCR
      results and detection of the VlsE protein with IgG-immunoblot (0.001 < p < 0.01).
      In conclusion, the results of the present study suggest that antibodies of IgG
      class are the most reliable marker in laboratory diagnostics of Lyme borreliosis,
      in particular those directed against VlsE surface protein of Borrelia burgdorferi
      sensu lato.

PMID- 17196007
TI  - Antifungal efficacy of hydrogen peroxide in dental unit waterline disinfection.
AB  - The concentration and composition of fungal flora in dental unit waterlines
      (DUWL) were evaluated. For this purpose, water samples from unit reservoirs and
      high-speed handpieces, and biofilm samples from the waterline walls from units
      were collected. Subsequently, analogous samples from DUWL were taken before and
      after disinfection using agent containing hydrogen peroxide. In the examined
      samples, the yeast-like fungi Candida albicans and Candida curvata were found.
      The following species of mould were also identified: Aspergillus amstelodami,
      Aspergillus fumigatus, Aspergillus glaucus group, Aspergillus (=Eurotium
      herbariorum) repens, Citromyces spp., Geotrichum candidum, Penicillium (glabrum)
      frequentans, Penicillium pusillum, Penicillium turolense and Sclerotium
      sclerotiorum (Sclerotinia sclerotiorum). Before disinfection, Candida curvata and
      Candida albicans constituted the greatest proportion of the total fungi in the
      reservoirs water; in the water of handpieces--Candida albicans and Aspergillus
      glaucus group; and in the biofilm samples--Aspergillus glaucus group and Candida
      albicans. After disinfection, in all 3 kinds of samples, Candida albicans
      prevailed, constituting from 31.2-85.7 % of the total fungi. The application of
      agent containing hydrogen peroxide caused a significant decrease both in the
      number of total fungi and individual fungal species, which confirms the product
      effectiveness in fungal decontamination of DUWL.

PMID- 17196008
TI  - Prevalence of Babesia microti in Ixodes ricinus ticks from Lublin region (eastern
      Poland).
AB  - A total of 1,367 Ixodes ricinus ticks collected from 5 districts of the Lublin
      region (eastern Poland) were examined for the presence of Babesia microti DNA by
      PCR and nested-PCR. As many as 74 ticks (5.4 %) were found to be infected with
      Babesia microti. The infection rate varied significantly with stage/sex of ticks
      (chi (2) =16.48543, df=2, p < 0.000264). The infection rates in females and males
      amounted to 6.4 % and 8.8 % respectively and were significantly higher (p=0.006
      and p=0.0001 respectively) compared to minimum infection rate in nymphs that was
      equal to 2.8 %. The prevalence of infection showed also a significant variability
      depending on geographic location within the Lublin region (chi(2) =18.62812,
      df=4, p < 0.000932). The highest rates of infection with Babesia microti were
      noted in ticks collected from the areas of Pulawy district situated in the
      northern part of region and the suburban Lublin district situated in the central
      part of the region (8.0 % and 7.3 % respectively). Mediocre infection rates
      (respectively 3.4 % and 3.3 %) were found in ticks from the Parczew and Wlodawa
      districts situated in eastern part of the region and covered with humid lakeland
      forests. The lowest infection rate (0.5 %) was noted in ticks from the Zamosc
      district situated in southern part of the region. In conclusion, the infection
      rate of Ixodes ricinus ticks with Babesia microti found in this study is higher
      compared to the majority of data reported by Polish and other European authors,
      and indicates a potential risk of human infection during occupational or
      recreational exposure to tick bite.

PMID- 17196010
TI  - Post-exposure anti-rabies prophylaxis in Lublin province (Eastern Poland) in 2004
      2005.
AB  - Rabies is considered a disease of the highest mortality rate and all humans are
      vulnerable to infection. Specific anti-rabies immunoprophylaxis is the only
      efficient method of protection. The analysis of indications for active alone and
      active and passive immunization among patients reported to the dispensary of
      rabies prophylaxis in the Department of Infectious Diseases of Medical University
      of Lublin (eastern Poland) in 2004-2005 is presented. Prophylactic procedures
      were applied in 120 persons (14.98 % of overall number consulted). Passive
      immunization, i.e. rabies immune globulin, was administered in 1 person (0.12 %).
      In 2004, 64 persons (7.99 %) received active vaccination, and 56 patients (6.99
      %) were vaccinated in 2005. Most of vaccinated patients lived in an urban area
      where the risk of rabies should be lower; however, in cities like Lublin there is
      a higher risk of being bitten by homeless animals. The most common species with
      rabies suspicion were dogs and cats. The decrease in the number of patients
      bitten by animals with confirmed rabies in Lublin province, and of the number of
      cases of animal rabies may indicate that oral vaccination of red foxes,
      representing a main reservoir of rabies virus in Poland, has been shown to be
      effective.

PMID- 17196009
TI  - Legionella and other gram-negative bacteria in potable water from various rural
      and urban sources.
AB  - A total of 107 potable water samples were collected from various rural and urban
      sources located in the Lublin region (eastern Poland). 54 samples from rural
      sources comprised 32 samples of untreated well water and 22 samples of treated
      (chlorinated) tap water from rural dwellings distributed by the municipal water
      supply system (MWSS). 53 samples of treated water from urban sources were
      supplied by the city of Lublin MWSS. They comprised: 11 samples of tap water from
      offices and shops, 8 samples of tap water from dwellings, 19 samples from
      showerheads in health care units, and 15 samples from the outlets of medical
      appliances used for hydrotherapy in a rehabilitation centre. Water samples were
      examined for the presence and species composition of Legionella, Yersinia, Gram
      negative bacteria belonging to family Enterobacteriaceae (GNB-E) and Gram
      negative bacteria not belonging to family Enterobacteriaceae (GNB-NE), by
      filtering through cellulose filters and culture on respectively GVPC, CIN, EMB
      and tryptic soya agar media. Legionella was recovered from samples of well water,
      tap water from rural dwellings, tap water from urban dwellings, and water from
      medical appliances - with the isolation frequency of 27.8-50.0 %, and the low
      concentrations ranging from 0.7-13.3 x 10 (1) cfu/l. No Legionella strains were
      detected in tap water from offices and shops, and in water from showerheads in
      health care units. Strains of the Legionella pneumophila types 2-14 predominated,
      forming 89.9 % of total Legionella isolates, while other species of Legionella
      formed 10.1 %. Neither Legionella pneumophila type 1 strains nor Yersinia strains
      were isolated from the examined water samples. The isolation frequency and mean
      concentration of GNB-E in water samples from rural sources was significantly
      greater than in water samples from urban sources (respectively 61.1 % vs. 20.8 %,
      17.1 vs. 3.4 x 10(1) cfu/l, p < 0.001). Isolation frequency of GNB-NE in water
      samples from rural sources was significantly greater compared to that from urban
      sources (77.8 % vs. 47.2 %, p < 0.01), but there was no significant difference in
      the concentration of GNB-NE in both sample sets. A significant correlation was
      found between concentrations of Legionella and GNB-NE for total MWSS water
      samples (p < 0.001), but not for the total well water samples. Altogether 34 GNB
      E and GNB-NE species and/or genera were identified in the examined samples, out
      of which 21 were potentially pathogenic. Enterobacter spp., Klebsiella spp.,
      Serratia spp., and Pantoea agglomerans were most common among GNB-E, while
      Acinetobacter spp. and species of Pseudomonadaceae family predominated among GNB
      NE.

PMID- 17196012
TI  - Exposure of workers to mites in Finnish groceries.
AB  - We assessed the mite exposure of workers in Finnish groceries by collecting
      samples of settled dust in 5 different grocerys. Mites were counted and
      identified microscopically. Mite allergen (Der p 1 and Der f 1) content of dust
      was analyzed with 2-site ELISA. Mites were found in 20-100 % of the samples, both
      from storage and salesrooms. Seven samples (8 %) contained more than 100 mites
      per gram dust and 3 additional samples (6 %) more than 500 mites per gram dust,
      the suggested limits for mite sensitization and acute allergic symptoms,
      respectively. Most of the mites were storage mites belonging to Astigmata
      (Acaridae, Glycyphagidae) or Prostigmata (tarsonemids). House dust mites were
      found only occasionally. One dust sample out of 15 contained Der p 1, and none
      contained Der f 1.

PMID- 17196013
TI  - Effect of microclimate on bacterial count and airborne emission from dairy barns
      on the environment.
AB  - The main microclimate parameters, i.e. bacterial count and airborne emission to
      the immediate environment, were analyzed in a dairy barn. Air temperature,
      relative humidity and air flow velocity were measured on an attested Testo 400
      device (Testo Inc., Germany). Air samples were collected by use of a Merck MAS
      100 device (Merck KgaA, Darmstadt, Germany) onto a commercially available
      nutrient Columbia agar (Biolife, Milan, Italy) and incubated for 24 h in an
      incubator at 37 degrees C work temperature. Measurements were carried out once a
      week in the morning, at noon, and in the evening during October and November
      2002. In the barn, measurements were performed in the animal housing area along
      the feedlot, and outside the barn at a distance of 5 m, 25 m and 50 m eastward
      and westward from the barn. The measured dairy barn temperature ranged from 11.2
      degrees C to 13.1 degrees C, relative humidity from 71.3-78.6 %, and air flow
      velocity from 0.09-0.11 m/s. The mean value of total bacterial count in the barn
      air ranged from 2.82 x 10 (4) cfu/m(3) at noon to 7.76 x 10(4) cfu/m(3) in the
      evening. Bacterial count decreased at particular measuring sites outside the
      barn, with Wilcoxon matched pair test showing statistical significance (p < 0.05)
      at a distance of 5 m eastward and 5 m westward of the barn.

PMID- 17196014
TI  - Occurrence of hard ticks in dogs from Warsaw area.
AB  - Ticks are known as a vector of many viral, bacterial, rickettsial and protozoan
      infections of dogs. The threat with particular tick-transmitted disease depends
      very much on the tick species which feeds on the dog. In this paper we present
      results of research designed to identify tick species which attack dogs in the
      Warsaw area. Ticks were collected from dogs presented for medical examination in
      veterinary clinics in different parts of Warsaw. All of 590 tick specimens found
      on dogs belonged to the family Ixodidae (hard ticks). The majority (64.6 %) of
      the collected ticks were identified as Dermacentor reticulatus--vector of Babesia
      canis. The other tick species found on examined dogs was Ixodes ricinus. The male
      to female ratio was more than 3 times higher in D. reticulatus than in I.
      ricinus.

PMID- 17196016
TI  - Trends in Mycology. Proceedings of the one day meeting, Braga, Portugal, 23
      September 2005.

PMID- 17196015
TI  - Endotoxin, (1 --> 3)-beta-D-glucans and fungal extra-cellular polysaccharides in
      New Zealand homes: a pilot study.
AB  - Bacterial endotoxin, fungal (1 --> 3)-beta-D-glucans, and extracellular
      polysaccharides from Aspergillus and Penicillium (EPS-Asp/Pen) have been
      suggested to be stable markers of microbial exposure. This paper describes a
      pilot study in which we measured endotoxin, (1 --> 3)-beta-D-glucans, EPS-Asp/Pen
      and mite allergen in house dust collected in 32 homes in Wellington, New Zealand.
      Endotoxin (GM 60,295 EU/g; GSD 2.4) and glucan (GM 2,687 microg/g; GSD 1.5)
      levels were higher in comparison to previous international studies, whereas EPS
      Asp/Pen levels (37,347 Units/g; GSD 1.9) appeared comparable. Concentrations
      expressed per square meter were highly correlated among the measured components
      (p < 0.05). When expressed per gram of dust only (1 --> 3)- beta -D-glucans and
      EPS-Asp/Pen were correlated (r=0.55, p < 0.01; n=32). Endotoxin and glucan levels
      were higher (borderline statistically significant; p < 0.10) in homes with self
      reported water damage. A positive association (p < 0.10) was also found for dust
      mite and a combination of self-reported mould, dampness and water damage. EPS
      levels were higher in homes where residents indicated the presence of mould spots
      on the wall, but this did not reach statistical significance. In conclusion,
      levels of microbial contaminants in a small random sample of New Zealand homes
      were high and weakly associated with water damage.

PMID- 17196017
TI  - Pandora's mycological box: molecular sequences vs. morphology in understanding
      fungal relationships and biodiversity.
AB  - Fundamental reappraisals of diverse traditional ideas in mycology have become
      necessary as a result of molecular insights. These different insights are
      discussed in relation to: the positions of microsporidia, slime moulds and
      oomycetes; the basal position of lichen fungi in the evolution of ascomycetes
      forming fruit bodies; remodelling of orders and families; changed generic
      concepts; the issue of whether permitting a dual nomenclature for the different
      states of pleomorphic fungi should be continued; and the recognition of
      additional cryptic species within a "species". The molecular data has
      necessitated a reassessment of the systematic importance of many types of
      characters. Also, the techniques open exciting horizons and undreamed of
      abilities through being able to identify non-sporing fungi in ecological samples
      and plant material, and revealing unexpected levels of diversity in hitherto
      little-explored habitats. Major advances in understanding how fungi operate
      through total genomic approaches can be anticipated as more are completely
      sequenced. The Pandora's box of molecular surprises is to be seen as one of
      blessings and not one of miseries and evils.

PMID- 17196018
TI  - Multilocus sequence analysis of Penicillium and Eupenicillium species.
AB  - Taxonomy of Hyphomycetes has always been a challenging problem, with experts
      viewing species in different ways and modifying the taxonomy of groups to reflect
      their best evaluation of species limits and concepts. The advent of phylogenetic
      analysis, relatively easy DNA sequencing techniques and PCR has provided an
      opportunity for mycology to move from a strictly morphological analysis of
      species to phylogenetic analysis of DNA sequences. Phylogenetic theory dictates
      that data from different loci will produce congruent or at least non
      contradictory evolutionary histories of a clonal lineage. Tests of tree
      congruence such as the index of association can show whether lineages are clonal,
      and has revealed that some species long thought to be clonal are cryptically
      recombining. Genealogical concordance phylogenetic species recognition allows
      unambiguous identification of species boundaries.

PMID- 17196019
TI  - Fungi in bottled water: a case study of a production plant.
AB  - A one-year fungal survey of a water bottling plant was conducted in order to
      evaluate the incidence and fluctuations of the mycobiota. The dominant fungal
      genera in order of highest numbers isolated were Penicillium, Cladosporium and
      Trichoderma followed by Aspergillus, Paecilomyces, and others. As expected, the
      highest number of isolates were collected during the warmer months, particularly
      May and June. Indeed during these two months there were more fungi present in the
      water, indicating that during those times of the year when fungal contamination
      is high, 0.4 mm filters should be changed on a more regular basis. In order to
      assess whether contamination was single or multi-loci, molecular methods based on
      the PCR were used for Penicillium brevicompactum. Overall, fungal contamination
      arose from multiple sources. Some P. brevicompactum strains were very "alike" and
      were detected during different sampling times, indicating that they were endemic
      to the plant. There was no evidence to suggest that fungi detected in the source
      water passed through to other parts of the plant. However, there was evidence
      that fungal strains isolated from the water filter were detected elsewhere in the
      factory, confirming the need to change filters more regularly during periods of
      high fungal contamination. In order to improve quality control a HACCP programme
      was implemented and Best Practice Guidelines introduced.

PMID- 17196020
TI  - PCR-RFLP of ITS rDNA for the rapid identification of Penicillium subgenus
      Biverticillium species.
AB  - RFLP of ITS rDNA is proposed as a useful tool for molecular identification of the
      most common species of biverticillate penicillia. 60 isolates were analysed
      representing 13 species and 21 unique sequences were produced. The combination of
      five restriction enzymes was successful in separating 12 species. However, the
      variety Penicillium purpurogenum var. rubrisclerotium remained indistinguishable
      from Penicillium funiculosum. P. funiculosum appeared as the most confused
      species, being mis-identified with Penicillium miniolutum and Penicillium
      pinophilum, which were originally part of the species, and with P. purpurogenum
      perhaps because of the common production of red pigment. Penicillium variabile
      was difficult to investigate as introns were found on half of the isolates.
      Penicillium piceum, Penicillium rugulosum, Penicillium loliense, Penicillium
      erythromellis and P. purpurogenum were homogeneous from molecular and
      morphological positions and corresponded to a well circumscribed taxon.
      Furthermore, intraspecific variability was evidenced within P. pinophilum and P.
      funiculosum. The ex-type isolate of P. funiculosum produced a unique pattern. The
      method is sensitive, rapid and inexpensive and can be used for isolate
      identification of the biverticillate species. It is recommended particularly when
      many isolates have to be authentificated prior to analysis for phylogenetic
      assessment or population genetics.

PMID- 17196021
TI  - Penicillium glabrum cork-colonising isolates - preliminary analysis of their
      genomic similarity.
AB  - The cork stopper manufacturing process includes an operation, known as
      stabilisation, by which humid cork slabs are extensively colonised by fungi. The
      effects of fungal growth on cork are not completely understood although they are
      considered to be involved in the so-called "cork taint" of wine. It is essential
      to (a) identify environmental constraints which define the appearance of the
      colonising fungal species and (b) trace their origin to the forest and/or the
      manufacturing space. The present article correlates two sets of data, from
      consecutive years and the same season, of systematic sampling of two
      manufacturing units, located in the North and South of Portugal. Chrysonilia
      sitophila dominance was confirmed, followed by a high diversity of Penicillium
      species. Penicillium glabrum, which was found in all samples, was the most
      frequently isolated species. P. glabrum intra-species variability was
      investigated using DNA fingerprinting techniques revealing highly discriminative
      polymorphic markers in the genome. Cluster analysis of P. glabrum data was
      discussed in relation to the geographical location of strains, and results
      suggest that P. glabrum arise from predominantly the manufacturing space,
      although cork specific fungi can contribute.

PMID- 17196022
TI  - A practical approach for identifications based on mycotoxin characters of
      Penicillium.
AB  - The taxonomy of the penicillia is unstable particularly in the important
      antibiotic and mycotoxin-producing subgenus Penicillium. There are difficulties
      relating identifications to mycotoxin production. Also, the validity of dual
      nomenclature for pleomorphic fungi is under discussion increasingly. Patulin is
      an important mycotoxin produced by various fungi and has strict limits in the
      European Union. The mycotoxin and/or the isoepoxydon dehydrogenase (IDH) gene of
      the metabolic pathway have been assessed in 318 strains predominately of subgenus
      Penicillium. These data were used to classify the isolates. Subgenus Penicillium
      contained most of the IDH and patulin positives. The species and varieties in
      subgenus Penicillium which were associated with patulin detection can be reduced
      to one name, viz. Penicillium Pen p+ (p = patulin). This has been extended to
      other mycotoxin producing penicillia to indicate the scope of the scheme. The
      classification will lead to the number of taxa being reduced, while avoiding
      species names and hence dual nomenclature. Culture independent analysis of
      environmental samples is mentioned. The scheme could be used with advantage for
      other fungi.

PMID- 17196023
TI  - Pigment chemistry, taxonomy and phylogeny of the Hypoxyloideae (Xylariaceae).
AB  - The Hypoxyloideae (Xylariaceae with Nodulisporium-like anamorphs) were evaluated
      by a morphological and HPLC-based chemotaxonomic survey of more than 2000
      specimens and cultures. Conspecificity of recent records with ancient type
      specimens were established in many cases by HPLC, since their characteristic
      metabolites may remain stable for over 200 years. Most constitute novel natural
      products that were identified in the course of concurrent "mycochemical" studies.
      A comparison of HPLC profiles considering relationships within the Hypoxyloideae
      as inferred from the biogenesis of these pigments agreed fairly with concurrent
      molecular phylogenetic studies, based on sequences of actin, beta-tubulin, and
      5.8S/ITS nrDNA genes. Anamorphic morphology and secondary metabolism of cultures
      agreed well at generic level and above. A combination of chemical and
      morphological traits is favored over PCR-based approaches for species
      discrimination, if only relatively few taxa of these diverse genera have been
      sequenced. An overview on the chemical structures and biological activities of
      the characteristic metabolites is provided, their ecological importance is
      discussed, and the utility of chemotaxonomy to support and predict phylogenetic
      relationships in the Hypoxyloidae is demonstrated. A polythetic approach is most
      useful to elucidate the phylogeny of the Xylariaceae. Chemotaxonomy to assess
      fungal biodiversity has considerable utility.

PMID- 17196024
TI  - Application of classification-tree models to characterize the mycobiota of grapes
      on the basis of origin.
AB  - Classification-tree (CT) models are a simple and robust exploratory data analysis
      technique that can be used in classification, regressions and summaries of data.
      They distill complex ecological relationships into simplified rules and identify
      the species necessary for sample classification on the basis of detailed
      ecological inventories. The usefulness of this technique to characterize and
      represent differences in the grape mycobiota of distinct origins was evaluated.
      Grapes from four Portuguese winemaking regions were selected for a 3-year study:
      Alentejo, Douro, Ribatejo and Vinhos Verdes. The mycobiota of grapes was assessed
      with plating methods and the frequencies of isolations of the fungal taxa
      identified in 32 samples were used as a training dataset. The CT algorithm
      selected the fungal taxa and respective frequencies to classify grapes according
      to its region of origin. The ten-fold cross-validation technique was used for
      model evaluation. The success rate of the model was quantified and expressed in
      the number of correctly classified samples overall and into region. Furthermore,
      model refinement was performed using attribute selection algorithms and class
      redefinition. A simple tree model was generated that classified grapes into three
      regional origins: Douro, South (Alentejo and Ribatejo classes together) and
      Vinhos Verdes, on the basis of the incidence of Aspergillus niger aggregate and
      Penicillium thomii in samples with an accuracy of 82%. The merits and demerits of
      these models are discussed.

PMID- 17196025
TI  - Efficacy of plant extracts against stored-products fungi.
AB  - The fungistatic activity of six aqueous extracts of plants were tested against
      Aspergillus candidus, Aspergillus niger, Penicillium sp. and Fusarium culmorum.
      The plants were, chamomile (Anthemis nobilis L.), cinnamon (Cinnamomum verum J.
      Presl.), French lavender (Lavandula stoechas L.), garlic (Allium sativum L.),
      malva (Malva sylvestris L.) and peppermint (Mentha piperita L.). The more
      concentrated extracts of chamomile and malva inhibited totally the growth of the
      tested fungi with malva the most effective one.

PMID- 17196026
TI  - Marine fungi from Mira river salt marsh in Portugal.
AB  - The occurrence of fungi in the Mira salt marsh, Portugal was investigated for 12
      months. Baits of Spartina maritima stems were exposed to permanent or temporary
      submersion at the upper and lower limits of the intertidal zone. The baits were
      observed for fruit bodies and spores directly and after incubation in moist
      chambers. Twenty six marine species were identified (17 Ascomycota, two
      Basidiomycota and seven mitosporic fungi). Twenty four are new records for
      Portugal. Nia globospora Barata and Basilio was published as a new species.
      Species were characterized with respect to frequency of occurrence, colonization
      capability and substrate succession. The diversity and similarity indexes of the
      fungi under different conditions were determined.

PMID- 17196027
TI  - Ambrosia fungi in the insect-fungi symbiosis in relation to cork oak decline.
AB  - Ambrosia fungi live associated with beetles (Scolytidae and Platypodidae) in host
      trees and act as a food source for the insects. The symbiotic relation is
      important to the colonizing strategies of host trees by beetles. Ambrosia fungi
      are dimorphic: they grow as ambrosial form and as mycelium. The fungi are highly
      specialized, adapted to a specific beetle and to the biotope where they both
      live. In addition other fungi have been found such as tree pathogenic fungi that
      may play a role in insects host colonization success. Saprophytic fungi are also
      present in insects galleries. These may decompose cellulose and/or be
      antagonistic to other less beneficial fungi. This paper summarizes the importance
      of ambrosia fungi and the interaction with insects and hosts. The possibility of
      the transport of pathogenic fungi by Platypus cylindrus to cork oak thus
      contributing for its decline is discussed.

PMID- 17196029
TI  - Notes on a plant parasite fungus in Portugal: Gymnosporangium cornutum.
AB  - A rust fungus identified as Gymnosporangium cornutum was found on Sorbus
      aucuparia in Serra da Estrela (Manteigas), and the disease was severe at that
      location. Despite the abundance and worldwide occurrence of the genus
      Gymnosporangium, studies in Portugal are still limited.

PMID- 17196028
TI  - New and simple plate test for screening relative transfructosylation activity of
      fungi.
AB  - Several microorganisms are reported to have transfructosylation activity due to
      fructosyltransferase and/or fructofuranosidase activities. However, the search
      for other fungi with higher transfructosylation activity remains a challenge. So,
      a presumptive and indirect colorimetric plate assay for the evaluation of
      transfructosylation activity in fungi was developed which involved the
      simultaneous determination in the same plate of glucose and fructose released
      from sucrose. The method entailed the (a) glucose oxidase-peroxidase coupled
      reaction using phenol and 4-aminoantipyrine for determination of glucose; and (b)
      fructose dehydrogenase oxidation in the presence of a tetrazolium salt for
      determination of fructose. The presence of enzymes with transfructosylation
      activity was identified by the formation of pink (presence of glucose) and blue
      (presence of fructose) halos around the fungal colony. In conclusion, the results
      showed that the method is suitable for screening a large number of fungi due to
      its simplicity, reproducibility and rapidity and also gives a relative
      quantitative idea of the transfructosylation activity of different fungi species.

PMID- 17196031
TI  - The genome: An outsider's view.

PMID- 17196030
TI  - FISH and Calcofluor staining techniques to detect in situ filamentous fungal
      biofilms in water.
AB  - Filamentous fungi are a ubiquitous and diverse group of eukaryotic organisms and
      may contribute, along with bacteria, yeasts, protozoa and viruses, to the
      formation of biofilms in water distribution systems. However, fungal involvement
      in biofilms has not been demonstrated unambiguously. Furthermore, these fungi may
      be responsible for the production of tastes, odours and mycotoxins in drinking
      water making their early detection important. The detection of fme these problems
      a combination of two fluorescent techniques for direct detection was tested: (a)
      Fluorescence In Situ Hybridization (FISH) employing the universal rRNA probe
      EUK516, labelled with the red Cy3, followed by (b) staining with Calcofluor White
      MR2 fluorescent dye which stains fungal cell walls blue. Pure cultures of
      Penicillium brevicompactum were used to establish the methods followed by
      separate experiments with real water biofilm samples in PVC-C and cast iron
      coupons. FISH demonstrated eukaryotic microrganisms after approximately 5 h while
      the calcofluor method revealed chitinous filamentous structures in less than one
      hour. When the two methods were combined, additional resolution was obtained from
      the images of filamentous walls (blue) with intact protoplasm (red). In
      conclusion, FISH and Calcofluor staining provide rapid, direct and unambiguous
      information on the involvement of ff in biofilms which form in water.

PMID- 17196032
TI  - Modularity and dynamics of cellular networks.

PMID- 17196033
TI  - Prediction of amyloidogenic and disordered regions in protein chains.
AB  - The determination of factors that influence protein conformational changes is
      very important for the identification of potentially amyloidogenic and disordered
      regions in polypeptide chains. In our work we introduce a new parameter, mean
      packing density, to detect both amyloidogenic and disordered regions in a protein
      sequence. It has been shown that regions with strong expected packing density are
      responsible for amyloid formation. Our predictions are consistent with known
      disease-related amyloidogenic regions for eight of 12 amyloid-forming proteins
      and peptides in which the positions of amyloidogenic regions have been revealed
      experimentally. Our findings support the concept that the mechanism of amyloid
      fibril formation is similar for different peptides and proteins. Moreover, we
      have demonstrated that regions with weak expected packing density are responsible
      for the appearance of disordered regions. Our method has been tested on datasets
      of globular proteins and long disordered protein segments, and it shows improved
      performance over other widely used methods. Thus, we demonstrate that the
      expected packing density is a useful value with which one can predict both
      intrinsically disordered and amyloidogenic regions of a protein based on sequence
      alone. Our results are important for understanding the structural characteristics
      of protein folding and misfolding.

PMID- 17196034
TI  - Stern-judging: A simple, successful norm which promotes cooperation under
      indirect reciprocity.
AB  - We study the evolution of cooperation under indirect reciprocity, believed to
      constitute the biological basis of morality. We employ an evolutionary game
      theoretical model of multilevel selection, and show that natural selection and
      mutation lead to the emergence of a robust and simple social norm, which we call
      stern-judging. Under stern-judging, helping a good individual or refusing help to
      a bad individual leads to a good reputation, whereas refusing help to a good
      individual or helping a bad one leads to a bad reputation. Similarly for tit-for
      tat and win-stay-lose-shift, the simplest ubiquitous strategies in direct
      reciprocity, the lack of ambiguity of stern-judging, where implacable punishment
      is compensated by prompt forgiving, supports the idea that simplicity is often
      associated with evolutionary success.

PMID- 17196035
TI  - Targeting neuropilin-1 to inhibit VEGF signaling in cancer: Comparison of
      therapeutic approaches.
AB  - Angiogenesis (neovascularization) plays a crucial role in a variety of
      physiological and pathological conditions including cancer, cardiovascular
      disease, and wound healing. Vascular endothelial growth factor (VEGF) is a
      critical regulator of angiogenesis. Multiple VEGF receptors are expressed on
      endothelial cells, including signaling receptor tyrosine kinases (VEGFR1 and
      VEGFR2) and the nonsignaling co-receptor Neuropilin-1. Neuropilin-1 binds only
      the isoform of VEGF responsible for pathological angiogenesis (VEGF165), and is
      thus a potential target for inhibiting VEGF signaling. Using the first
      molecularly detailed computational model of VEGF and its receptors, we have shown
      previously that the VEGFR-Neuropilin interactions explain the observed
      differential effects of VEGF isoforms on VEGF signaling in vitro, and
      demonstrated potent VEGF inhibition by an antibody to Neuropilin-1 that does not
      block ligand binding but blocks subsequent receptor coupling. In the present
      study, we extend that computational model to simulation of in vivo VEGF transport
      and binding, and predict the in vivo efficacy of several Neuropilin-targeted
      therapies in inhibiting VEGF signaling: (a) blocking Neuropilin-1 expression; (b)
      blocking VEGF binding to Neuropilin-1; (c) blocking Neuropilin-VEGFR coupling.
      The model predicts that blockade of Neuropilin-VEGFR coupling is significantly
      more effective than other approaches in decreasing VEGF-VEGFR2 signaling. In
      addition, tumor types with different receptor expression levels respond
      differently to each of these treatments. In designing human therapeutics, the
      mechanism of attacking the target plays a significant role in the outcome: of the
      strategies tested here, drugs with similar properties to the Neuropilin-1
      antibody are predicted to be most effective. The tumor type and the
      microenvironment of the target tissue are also significant in determining
      therapeutic efficacy of each of the treatments studied.

PMID- 17196036
TI  - Fungal invasion of normally non-phagocytic host cells.
AB  - Many fungi that cause invasive disease invade host epithelial cells during
      mucosal and respiratory infection, and subsequently invade endothelial cells
      during hematogenous infection. Most fungi invade these normally non-phagocytic
      host cells by inducing their own uptake. Candida albicans hyphae interact with
      endothelial cells in vitro by binding to N-cadherin on the endothelial cell
      surface. This binding induces rearrangement of endothelial cell microfilaments,
      which results in the endocytosis of the organism. The capsule of Cryptococcus
      neoformans is composed of glucuronoxylomannan, which binds specifically to brain
      endothelial cells, and appears to mediate both adherence and induction of
      endocytosis. The mechanisms by which other fungal pathogens induce their own
      uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species
      and the Zygomycetes, invade endothelial cells from the abluminal surface during
      the initiation of invasive disease, and subsequently invade the luminal surface
      of endothelial cells during hematogenous dissemination. Invasion of normally non
      phagocytic host cells has different consequences, depending on the type of
      invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial
      cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial
      cells. This review summarizes the mechanisms by which diverse fungal pathogens
      invade normally non-phagocytic host cells and discusses gaps in our knowledge
      that provide opportunities for future research.

PMID- 17196038
TI  - The fittest versus the flattest: experimental confirmation of the quasispecies
      effect with subviral pathogens.
AB  - The "survival of the fittest" is the paradigm of Darwinian evolution in which the
      best-adapted replicators are favored by natural selection. However, at high
      mutation rates, the fittest organisms are not necessarily the fastest replicators
      but rather are those that show the greatest robustness against deleterious
      mutational effects, even at the cost of a low replication rate. This scenario,
      dubbed the "survival of the flattest", has so far only been shown to operate in
      digital organisms. We show that "survival of the flattest" can also occur in
      biological entities by analyzing the outcome of competition between two viroid
      species coinfecting the same plant. Under optimal growth conditions, a viroid
      species characterized by fast population growth and genetic homogeneity
      outcompeted a viroid species with slow population growth and a high degree of
      variation. In contrast, the slow-growth species was able to outcompete the fast
      species when the mutation rate was increased. These experimental results were
      supported by an in silico model of competing viroid quasispecies.

PMID- 17196037
TI  - Fz2 and cdc42 mediate melanization and actin polymerization but are dispensable
      for Plasmodium killing in the mosquito midgut.
AB  - The midgut epithelium of the mosquito malaria vector Anopheles is a hostile
      environment for Plasmodium, with most parasites succumbing to host defenses. This
      study addresses morphological and ultrastructural features associated with
      Plasmodium berghei ookinete invasion in Anopheles gambiae midguts to define the
      sites and possible mechanisms of parasite killing. We show by transmission
      electron microscopy and immunofluorescence that the majority of ookinetes are
      killed in the extracellular space. Dead or dying ookinetes are surrounded by a
      polymerized actin zone formed within the basal cytoplasm of adjacent host
      epithelial cells. In refractory strain mosquitoes, we found that formation of
      this zone is strongly linked to prophenoloxidase activation leading to
      melanization. Furthermore, we identify two factors controlling both phenomena:
      the transmembrane receptor frizzled-2 and the guanosine triphosphate-binding
      protein cell division cycle 42. However, the disruption of actin polymerization
      and melanization by double-stranded RNA inhibition did not affect ookinete
      survival. Our results separate the mechanisms of parasite killing from subsequent
      reactions manifested by actin polymerization and prophenoloxidase activation in
      the A. gambiae-P. berghei model. These latter processes are reminiscent of wound
      healing in other organisms, and we propose that they represent a form of wound
      healing response directed towards a moribund ookinete, which is perceived as
      damaged tissue.

PMID- 17196039
TI  - Functions of the nonsense-mediated mRNA decay pathway in Drosophila development.
AB  - Nonsense-mediated mRNA decay (NMD) is a cellular surveillance mechanism that
      degrades transcripts containing premature translation termination codons, and it
      also influences expression of certain wild-type transcripts. Although the
      biochemical mechanisms of NMD have been studied intensively, its developmental
      functions and importance are less clear. Here, we describe the isolation and
      characterization of Drosophila "photoshop" mutations, which increase expression
      of green fluorescent protein and other transgenes. Mapping and molecular analyses
      show that photoshop mutations are loss-of-function mutations in the Drosophila
      homologs of NMD genes Upf1, Upf2, and Smg1. We find that Upf1 and Upf2 are
      broadly active during development, and they are required for NMD as well as for
      proper expression of dozens of wild-type genes during development and for larval
      viability. Genetic mosaic analysis shows that Upf1 and Upf2 are required for
      growth and/or survival of imaginal cell clones, but this defect can be overcome
      if surrounding wild-type cells are eliminated. By contrast, we find that the PI3K
      related kinase Smg1 potentiates but is not required for NMD or for viability,
      implying that the Upf1 phosphorylation cycle that is required for mammalian and
      Caenorhabditis elegans NMD has a more limited role during Drosophila development.
      Finally, we show that the SV40 3' UTR, present in many Drosophila transgenes,
      targets the transgenes for regulation by the NMD pathway. The results establish
      that the Drosophila NMD pathway is broadly active and essential for development,
      and one critical function of the pathway is to endow proliferating imaginal cells
      with a competitive growth advantage that prevents them from being overtaken by
      other proliferating cells.

PMID- 17196041
TI  - Mapping determinants of gene expression plasticity by genetical genomics in C.
      elegans.
AB  - Recent genetical genomics studies have provided intimate views on gene regulatory
      networks. Gene expression variations between genetically different individuals
      have been mapped to the causal regulatory regions, termed expression quantitative
      trait loci. Whether the environment-induced plastic response of gene expression
      also shows heritable difference has not yet been studied. Here we show that
      differential expression induced by temperatures of 16 degrees C and 24 degrees C
      has a strong genetic component in Caenorhabditis elegans recombinant inbred
      strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No
      less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment
      interaction, here termed plasticity quantitative trait loci. In contrast, only 8%
      of an estimated 188 cis-acting genes showed such interaction. This indicates that
      heritable differences in plastic responses of gene expression are largely
      regulated in trans. This regulation is spread over many different regulators.
      However, for one group of trans-genes we found prominent evidence for a common
      master regulator: a transband of 66 coregulated genes appeared at 24 degrees C.
      Our results suggest widespread genetic variation of differential expression
      responses to environmental impacts and demonstrate the potential of genetical
      genomics for mapping the molecular determinants of phenotypic plasticity.

PMID- 17196040
TI  - Unraveling the genetics of human obesity.
AB  - The use of modern molecular biology tools in deciphering the perturbed
      biochemistry and physiology underlying the obese state has proven invaluable.
      Identifying the hypothalamic leptin/melanocortin pathway as critical in many
      cases of monogenic obesity has permitted targeted, hypothesis-driven experiments
      to be performed, and has implicated new candidates as causative for previously
      uncharacterized clinical cases of obesity. Meanwhile, the effects of mutations in
      the melanocortin-4 receptor gene, for which the obese phenotype varies in the
      degree of severity among individuals, are now thought to be influenced by one's
      environmental surroundings. Molecular approaches have revealed that syndromes
      (Prader-Willi and Bardet-Biedl) previously assumed to be controlled by a single
      gene are, conversely, regulated by multiple elements. Finally, the application of
      comprehensive profiling technologies coupled with creative statistical analyses
      has revealed that interactions between genetic and environmental factors are
      responsible for the common obesity currently challenging many Westernized
      societies. As such, an improved understanding of the different "types" of obesity
      not only permits the development of potential therapies, but also proposes novel
      and often unexpected directions in deciphering the dysfunctional state of
      obesity.

PMID- 17196043
TI  - Knight in common armor: an interview with Sir John Sulston by Jane Gitschier.

PMID- 17196042
TI  - A high-resolution map of synteny disruptions in gibbon and human genomes.
AB  - Gibbons are part of the same superfamily (Hominoidea) as humans and great apes,
      but their karyotype has diverged faster from the common hominoid ancestor. At
      least 24 major chromosome rearrangements are required to convert the presumed
      ancestral karyotype of gibbons into that of the hominoid ancestor. Up to 28
      additional rearrangements distinguish the various living species from the common
      gibbon ancestor. Using the northern white-cheeked gibbon (2n = 52) (Nomascus
      leucogenys leucogenys) as a model, we created a high-resolution map of the
      homologous regions between the gibbon and human. The positions of 100 synteny
      breakpoints relative to the assembled human genome were determined at a
      resolution of about 200 kb. Interestingly, 46% of the gibbon-human synteny
      breakpoints occur in regions that correspond to segmental duplications in the
      human lineage, indicating a common source of plasticity leading to a different
      outcome in the two species. Additionally, the full sequences of 11 gibbon BACs
      spanning evolutionary breakpoints reveal either segmental duplications or
      interspersed repeats at the exact breakpoint locations. No specific sequence
      element appears to be common among independent rearrangements. We speculate that
      the extraordinarily high level of rearrangements seen in gibbons may be due to
      factors that increase the incidence of chromosome breakage or fixation of the
      derivative chromosomes in a homozygous state.

PMID- 17196044
TI  - Acupuncture for depression: a randomized controlled trial.
AB  - OBJECTIVE: To assess the efficacy of acupuncture as an intervention for major
      depressive disorder (MDD). METHOD: Acupuncture was examined in 151 patients with
      MDD (DSM-IV) who were randomly assigned to 1 of 3 groups in a double-blind
      randomized controlled trial. The specific intervention involved Traditional
      Chinese Medicine (TCM)-style acupuncture with manual stimulation for depression;
      the control conditions consisted of (1) a nonspecific intervention using a
      comparable number of legitimate acupuncture points not specifically targeted to
      depressive symptoms and (2) a waitlist condition, which involved waiting without
      intervention for 8 weeks. After 8 weeks, all patients received the depression
      specific acupuncture. Each 8-week intervention regimen consisted of 12
      acupuncture sessions delivered in an acupuncturist's office in the community. The
      primary outcome measure was the 17-item Hamilton Rating Scale for Depression. The
      study was conducted from February 1998 to April 2002. RESULTS: Twenty patients
      terminated treatment before the completion of the 8-week intervention (13%) but
      not differentially by study group. Random regression models of the intent-to
      treat sample revealed that although patients receiving acupuncture improved more
      than those awaiting intervention, no evidence of differential efficacy of the
      depression-specific over nonspecific intervention was found. Response rates in
      acupuncture-treated patients were relatively low after 8 weeks (22% and 39% for
      specific and nonspecific intervention groups, respectively), with the response
      rate after the entire 16-week trial reaching 50%. CONCLUSION: Although TCM manual
      acupuncture is a well-tolerated intervention, results fail to support its
      efficacy as a monotherapy for MDD. It can't be ruled out that factors unique to
      the implementation of acupuncture in this research study may have limited the
      efficacy of interventions compared to those provided in naturalistic settings.
      CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00010517.

PMID- 17196045
TI  - A randomized, double-blind, active-control study of sertraline versus venlafaxine
      XR in major depressive disorder.
AB  - OBJECTIVE: Sertraline may produce dual neurotransmitter effects similar to the
      serotonin-norepinephrine reuptake inhibitors (SNRIs); however, it has been tested
      against an SNRI in only 1 previous study, and never at an optimal dose. The
      objective of the current multisite study was to compare relatively higher doses
      of sertraline (i.e., 150 mg/day) and venlafaxine extended release (XR) (225
      mg/day) in outpatients with major depressive disorder. METHOD: Subjects with DSM
      IV major depressive disorder were randomly assigned to 8 weeks of double-blind
      treatment with sertraline (N = 82) or venlafaxine XR (N = 78). The study ran from
      January 2002 through January 2003. The primary outcome measure was the Quality of
      Life Enjoyment and Satisfaction Questionnaire; secondary outcome variables
      included the 17-item Hamilton Rating Scale for Depression. RESULTS: Both
      treatments led to significant improvement in depressive symptoms and quality-of
      life measures. No significant differences were noted between treatment groups for
      final scores on the primary or secondary measures. The treatment groups did not
      differ significantly in the percentage of responders (sertraline = 55%,
      venlafaxine XR = 65%; intent-to-treat [ITT] sample) or remitters (sertra-line =
      38%, venlafaxine XR = 49%; ITT sample), although the proportions are similar to
      those found in earlier selective serotonin reuptake inhibitor (SSRI) vs.
      venlafaxine meta-analyses. In patients who achieved the maximum dose of drug and
      maintained it for 3 weeks, response rates were similar to those found at lower
      doses (sertraline = 59%, venlafaxine XR = 70%); however, remission rates for this
      sample were comparable for both drug groups (sertraline = 48%, venlafaxine XR =
      50%). CONCLUSIONS: The efficacies of sertraline and venlafaxine XR were
      comparable. Although response and remission rates did not differ statistically,
      the rates were analogous to those reported in previous meta-analyses. However, at
      clinically relevant higher doses, the remission rates were very similar. CLINICAL
      TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00179283.

PMID- 17196046
TI  - The boundary between hypochondriasis and obsessive-compulsive disorder: a cross
      sectional study from the Netherlands.
AB  - OBJECTIVE: To investigate similarities and differences between the symptom
      profiles of patients with hypochondriasis and those of patients with obsessive
      compulsive disorder (OCD) and to compare the contamination/cleaning OCD subtype
      to other OCD subtypes. METHOD: Between January 1998 and July 2002, 76 patients
      diagnosed with hypochondriasis (N = 31) or OCD (N = 45) (DSM-IV criteria) and 25
      subjects with no formal DSM-IV diagnosis were compared with regard to the extent
      of diagnosis-specific symptoms, the number and nature of physical symptoms, and
      whether these symptoms evoked fear. The analyses were repeated after subdividing
      the OCD patients into the contamination/cleaning and other OCD subgroups.
      RESULTS: Patients with hypochondriasis and OCD differed significantly from each
      other on the extent of diagnosis-specific symptoms (all p < .001). Patients with
      hypochondriasis reported significantly more obsessive-compulsive symptoms and
      patients with OCD reported significantly more hypochondriacal symptoms than did
      the healthy control-group members (all p < .05). Neither group differed
      significantly from the other on the number and nature of feared physical
      symptoms. The contamination/cleaning OCD subtype did not differ significantly
      from other OCD subtypes in either the severity of hypochondriacal symptoms or the
      number of feared physical symptoms. CONCLUSION: Hypochondriasis and OCD can be
      distinguished on the basis of diagnosis-specific symptoms, although they share a
      number of similarities. In addition, although patients with the
      contamination/cleaning OCD subtype tend to be afraid of contracting diseases, the
      differences between the symptom profiles of these patients and those of patients
      with hypochondriasis exceed the similarities. Our results confirm that the 2
      conditions are separable and valid diagnoses.

PMID- 17196047
TI  - Prediction of remission as a combination of symptomatic and functional remission
      and adequate subjective well-being in 2960 patients with schizophrenia.
AB  - OBJECTIVE: Recently, the Remission in Schizophrenia Working Group proposed
      symptomatic remission criteria and pointed to the lack of data regarding
      functional remission and quality of life in schizophrenia. This post hoc analysis
      of data from German patients in the Schizophrenia Outpatient Health Outcomes
      study assessed rates and predictors of symptomatic and functional remission as
      well as adequate subjective well-being/quality of life in a large cohort of
      patients with schizophrenia. METHOD: Data were collected in an observational 24
      month follow-up study of 2960 patients with DSM-IV-defined schizophrenia
      recruited between January and December 2001. Complete remission required that
      patients achieved symptomatic remission mirroring the Remission in Schizophrenia
      Working Group criteria, functional remission, and a level of adequate subjective
      well-being over at least 6 months. RESULTS: At endpoint, 47.2% of the patients
      achieved symptomatic remission, 26.6% achieved functional remission, and 42.2%
      achieved adequate subjective well-being. At endpoint, 12.8% were in complete
      remission. In 35.1% of patients, none of the 3 remission criteria were achieved.
      Only 8.7% of early nonremitted cases achieved remission at endpoint. Each single
      remission component as well as complete remission was mainly predicted by early
      remission within the first 3 months. First-line treatment with atypical
      antipsychotics increased the likelihood of complete remission compared to
      conventional antipsychotics. CONCLUSIONS: Despite advances in pharmacologic and
      psychosocial treatments in schizophrenia, close to 90% of the patients in this
      study did not fulfill the combined remission criteria. This was in part
      attributable to the low functional remission rate, particularly the low
      employment rate. The finding that the course of the disorder depends on early
      outcome not only in previously untreated but also in more chronically ill
      patients points toward a critical "window of opportunity" in the course of
      treatment.

PMID- 17196048
TI  - Adjunctive topiramate therapy in patients receiving a mood stabilizer for bipolar
      I disorder: a randomized, placebo-controlled trial.
AB  - OBJECTIVE: To investigate the efficacy and safety of topiramate versus placebo as
      adjunctive therapy for the outpatient management of bipolar I disorder. METHOD:
      In this 12-week, randomized, double-blind, placebo-controlled trial, adults with
      bipolar I disorder (DSM-IV criteria) experiencing a manic or mixed episode with a
      Young Mania Rating Scale (YMRS) score of >or= 18 while taking therapeutic levels
      of valproate or lithium received adjunctive topiramate or placebo. Topiramate was
      titrated from 25 to 400 mg/day over 8 weeks and was continued for 4 additional
      weeks. The study was conducted from October 2001 through October 2003. The
      primary outcome measure was the change in YMRS score from baseline to last study
      visit during the double-blind phase. RESULTS: The mean +/- SD change in YMRS
      score from baseline was -10.1 +/- 8.7 (-40.1%) in the topiramate group (N = 143)
      and -9.6 +/- 8.2 (-40.2%) in the placebo group (N = 144, p = .797). Greater than
      50% reduction in YMRS was achieved by 39% of the topiramate group and 38% of the
      placebo group (p = .914). No significant treatment differences were observed for
      secondary efficacy measures. Compared with adjunctive placebo, adjunctive
      topiramate did not worsen mania or induce depression. Paresthesia, diarrhea, and
      anorexia were more common in the topiramate group. The topiramate group achieved
      greater reductions than the placebo group in body weight (-2.5 vs. 0.2 kg, p <
      .001) and body mass index (-0.84 vs. 0.07 kg/m(2), p < .001). CONCLUSION: In
      patients treated with lithium or valproate, there was no difference in the
      reduction of YMRS score in the topiramate and placebo groups. Both groups showed
      declines of 40%. Topiramate reduced body weight significantly relative to placebo
      without worsening depressive or manic symptoms.

PMID- 17196049
TI  - Remission in first-episode psychosis: predictor variables and symptom improvement
      patterns.
AB  - BACKGROUND: Previous attempts to identify clinically useful predictors of
      treatment outcome in schizophrenia have been hampered by methodological
      inconsistencies, including a lack of standardized outcome measures. Recently
      proposed operationally defined criteria for remission provide an opportunity to
      readdress this topic. METHOD: We applied the remission criteria to a sample of 57
      subjects with first-episode psychosis (DSM-IV schizophrenia, schizoaffective
      disorder, or schizophreniform disorder), treated according to a fixed protocol in
      a prospective study. Subjects were recruited between April 1999 and January 2000
      and were followed for 2 years. Various demographic, baseline clinical, and early
      response variables were subjected to discriminant analysis for their ability to
      predict remission or nonremission. We also assessed the symptom improvement
      patterns over time and compared endpoint psychopathology in the remitters and
      nonremitters. RESULTS: A model incorporating neurologic soft signs, 6-week
      treatment response, duration of untreated psychosis, marital status, and Positive
      and Negative Syndrome Scale excited factor baseline score was able to correctly
      predict 89% of the remitters and 86% of the nonremitters. Symptom reduction at 6
      weeks, including core psychotic symptoms, was significant in both groups
      (remitters, p < .0001; nonremitters, p < .0001), although reduction was
      substantially greater in the remission group (p = .004). Thereafter, the
      remission group continued to improve (p < .01), while the nonremitting group
      failed to do so (p = .55). Considerable overlap of endpoint symptoms was
      observed, and depressive symptom scores were similar in remitters and
      nonremitters. CONCLUSION: A combination of demographic, baseline clinical, and
      acute treatment response variables may accurately predict treatment outcome.
      Persistent noncore psychotic symptoms in subjects meeting proposed remission
      criteria require further investigation.

PMID- 17196050
TI  - The brown longitudinal obsessive compulsive study: treatments received and
      patient impressions of improvement.
AB  - OBJECTIVE: The primary aim of this study was to assess the extent to which
      individuals with obsessive-compulsive disorder (OCD) received recommended doses
      of treatment and perceived a response to these treatments. METHOD: Participants
      were 293 adults with primary OCD (DSM-IV) who were enrolled in the Brown
      Longitudinal Obsessive Compulsive Study, a naturalistic, prospective study of
      course in OCD. Data were collected at intake interviews between June 2001 and
      October 2004. Patient impressions of response to treatments received were
      assessed using the Clinical Global Impressions-Improvement Scale-patient version.
      RESULTS: Of the 182 participants taking recommended doses of serotonin reuptake
      inhibitors (SRIs) at intake, 112 (62%) rated themselves as being very much or
      much improved. The remaining participants rated themselves as minimally improved,
      unchanged, or worse while taking recommended doses of SRIs. These participants (N
      = 70) reported receiving their current SRI for a mean (SD) of 2.7 (3.2) years.
      Twelve (29%) of the 42 participants receiving neuroleptic augmentation of SRIs
      reported a response. Thirty-eight percent of the sample received the recommended
      number of 13 sessions of cognitive-behavioral therapy (CBT) lifetime. Only 24%
      reported completing a continuous course of 13 weekly sessions. Eighteen (67%) of
      the 27 participants who received a course of CBT in the past year rated
      themselves as very much or much improved. CONCLUSIONS: In this large,
      naturalistic study of OCD, over one third of participants receiving recommended
      doses of SRIs did not perceive substantial long-term benefit from pharmaco
      therapy. Relatively few participants received recommended doses of CBT. Clinical
      implications and future directions are discussed.

PMID- 17196051
TI  - Incidence and time course of subsyndromal symptoms in patients with bipolar I
      disorder: an evaluation of 2 placebo-controlled maintenance trials.
AB  - BACKGROUND: Subsyndromal symptoms in bipolar disorder can cause significant
      functional impairment and are associated with relapse. METHOD: In this post hoc
      analysis from 2 randomized, double-blind, 18-month, placebo-controlled
      maintenance trials for bipolar I disorder (both trials were conducted between
      August 1997 and August 2001 and used DSM-IV criteria), the incidence, time
      course, and impact of pharmacotherapy on subsyndromal symptoms were examined.
      RESULTS: Subsyndromal symptoms occurred in approximately 25% of all visits.
      Compared with placebo (54.8%), a significantly higher mean percentage of visits
      in remission were observed with lamotrigine treatment (63.0%, p = .020) but not
      with lithium treatment (60.0%, p = .165). The median time to onset of
      subsyndromal symptoms for lamotrigine (N = 223), lithium (N = 164), and placebo
      (N = 188) was 15, 15, and 9 days, respectively. Compared with placebo, both
      lamotrigine and lithium significantly delayed the time from randomization to
      onset of subsyndromal symptoms (p = .046, lamotrigine vs. placebo; p = .033,
      lithium vs. placebo; p = .763, lamotrigine vs. lithium) and the time from onset
      of subsyndromal symptoms to subsequent mood episode (p = .037, lamotrigine vs.
      placebo; p = .023, lithium vs. placebo; p = .845, lamotrigine vs. lithium).
      Agreement between the polarities of the first-observed subsyndromal symptom and
      subsequent intervention for mood episode was statistically significant (p <
      .001). CONCLUSION: Subsyndromal symptoms are common during maintenance treatment
      and appear to be associated with relapse into an episode of the same polarity.
      Both lithium and lamotrigine delayed the onset of subsyndromal symptoms and the
      time from onset of subsyndromal symptoms to subsequent relapse. Further study to
      assess whether treatment intervention can minimize subsyndromal symptoms or
      prevent relapse is encouraged.

PMID- 17196052
TI  - Efficacy and tolerability of open-label topiramate in the treatment of sleep
      related eating disorder: a retrospective case series.
AB  - OBJECTIVE: Determine the efficacy and tolerability of topiramate in the treatment
      of sleep-related eating disorder (SRED). METHOD: This is a retrospective chart
      review of consecutive patients treated in an open-label trial of topiramate for
      SRED in a sleep disorders clinic. Patients were diagnosed according to the second
      edition of the International Classification of Sleep Disorders. Patients with a
      Clinical Global Impressions of Improvement (CGI-I) rating of "very much" or
      "much" improved were considered treatment responders. RESULTS: 30 subjects were
      prescribed topiramate, of whom 25 had at least 1 postbaseline follow-up
      appointment. The mean age of these 25 patients was 44 +/- 12 years, 76% were
      female, and the mean age at onset of SRED was 25.2 +/- 12.8 years. The mean dose
      of topiramate was 135 +/- 61.6 mg (range, 25-300 mg) over a mean period of 11.6
      +/- 11.4 months (range, 1-42 months). Over two thirds of the patients (17/25 or
      68%) were considered topiramate responders. Twenty-eight percent (7/25) of the
      patients lost more than 10% of body weight. Adverse events were reported by 84%
      (21/25) of patients. Nearly half (7/17 or 41%) of the responders discontinued
      topiramate after a mean of 12.4 months. CONCLUSION: In this open-label
      retrospective trial, topiramate was found to be very effective in reducing
      nocturnal eating in patients with chronic SRED. The tolerability of topiramate
      was an issue in some patients. Given the promise of this approach, but the
      limitations of this study, prospective, double-blind study of topiramate in a
      larger sample of patients with SRED is warranted.

PMID- 17196053
TI  - Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive
      compulsive disorder.
AB  - BACKGROUND: Anecdotal reports suggest that psychedelic agents may relieve
      symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study
      investigated the safety, tolerability, and clinical effects of psilocybin, a
      potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. METHOD: Nine
      subjects with DSM-IV-defined OCD and no other current major psychiatric disorder
      participated in up to 4 single-dose exposures to psilocybin in doses ranging from
      sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200
      microg/kg), and high (300 microg/kg) doses were assigned in that order, and a
      very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at
      any time after the first dose. Testing days were separated by at least 1 week.
      Each session was conducted over an 8-hour period in a controlled environment in
      an outpatient clinic; subjects were then transferred to a psychiatric inpatient
      unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS)
      and a visual analog scale measuring overall obsessive-compulsive symptom severity
      were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen
      Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1,
      4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to
      November 2004. RESULTS: Nine subjects were administered a total of 29 psilocybin
      doses. One subject experienced transient hypertension without relation to anxiety
      or somatic symptoms, but no other significant adverse effects were observed.
      Marked decreases in OCD symptoms of variable degrees were observed in all
      subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS
      score). Repeated-measures analysis of variance for all YBOCS values revealed a
      significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046),
      but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction
      of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted
      past the 24-hour timepoint. CONCLUSIONS: In a controlled clinical environment,
      psilocybin was safely used in subjects with OCD and was associated with acute
      reductions in core OCD symptoms in several subjects.

PMID- 17196054
TI  - Which factors predict placebo response in anxiety disorders and major depression?
      An analysis of placebo-controlled studies of escitalopram.
AB  - BACKGROUND: The placebo response rate has increased in several psychiatric
      disorders and is a major issue in the design and interpretation of clinical
      trials. The current investigation attempted to identify potential predictors of
      placebo response through examination of the placebo-controlled clinical trial
      database for escitalopram in 3 anxiety disorders and in major depressive disorder
      (MDD). METHOD: Raw data from placebo-controlled studies (conducted from 2002
      through the end of 2004) of escitalopram in patients meeting DSM-IV criteria for
      MDD and anxiety disorders (generalized anxiety disorder [GAD], social anxiety
      disorder [SAD], panic disorder) were used. Potential predictors examined were
      type of disorder, location of study, dosing regimen, number of treatment arms,
      gender of patients, and duration and severity of disorder. RESULTS: Placebo
      response (defined as the percent decrease from baseline in the reference scale)
      was higher in GAD and MDD studies conducted in Europe (p < .0001 and p = .0006,
      respectively) and was not associated with gender or duration of episode. In GAD,
      the placebo response rate was higher in a European fixed-dose study, which also
      had more treatment arms. In SAD and in U.S. specialist-treated MDD, a higher
      placebo response rate was predicted by decreased baseline disorder severity.
      CONCLUSION: Additional work is needed before definitive recommendations can be
      made about whether standard exclusion criteria in clinical trials of
      antidepressants, such as mild severity of illness, maximize medication-to-placebo
      differences. This analysis in a range of anxiety disorders and MDD suggests that
      there may be instances in which the predictors of placebo response rate
      themselves vary across different conditions.

PMID- 17196056
TI  - A cross-sectional study of the prevalence of cognitive and physical symptoms
      during long-term antidepressant treatment.
AB  - BACKGROUND: Antidepressant therapies have been associated with a variety of side
      effects of both physical and psychological nature. Until recently, however, the
      majority of the studies focusing on side effects of antidepressants have not
      routinely included assessment of cognitive side effects. The purpose of the
      present work is to examine cross-sectionally the prevalence of cognitive and
      physical side effects of antidepressants during long-term treatment of
      depression. METHOD: Patients at least 18 years of age who were deemed responders
      to antidepressant therapy following at least 3 months of treatment for major
      depressive disorder (MDD) (diagnosed according to DSM-IV criteria) and whose MDD
      was considered to be in partial or full remission were eligible for inclusion in
      this study. Eligible patients were enrolled between January 2003 and December
      2004. Study participants were administered the Harvard Department of
      Psychiatry/National Depression Screening Day (HANDS) scale, the Epworth
      Sleepiness Scale, the Brief Fatigue Inventory, the Massachusetts General Hospital
      Cognitive and Physical Functioning Questionnaire (CPFQ), and a study-specific
      questionnaire inquiring about the emergence of specific side effects such as
      apathy, fatigue, and inattentiveness. RESULTS: 117 MDD patients (mean +/- SD age:
      43.4 +/- 12.6 years; women: N = 78 [66.7%]) met criteria for response according
      to the HANDS (score < 9). Cognitive symptoms (apathy, inattentiveness,
      forgetfulness, word-finding difficulty, and mental slowing) were each reported on
      both the CPFQ and the study-specific questionnaire by more than 30% of the
      responders on antidepressants. The physical symptoms of fatigue and
      sleepiness/sedation were reported by over 40% of the responders on both the CPFQ
      and the study-specific questionnaire. A significant, positive relationship was
      found between the CPFQ and the severity of residual depressive symptoms as
      measured by the HANDS total score (F = 15.3, p = .0002). CONCLUSION: Physical and
      cognitive symptoms are frequently reported by MDD patients who have responded to
      antidepressants and are treated in the long term with these agents. It is likely
      that these symptoms are both side effects of the antidepressants as well as
      residual symptoms of MDD.

PMID- 17196057
TI  - Association between enhanced soluble CD40 ligand and proinflammatory and
      prothrombotic states in major depressive disorder: pilot observations on the
      effects of selective serotonin reuptake inhibitor therapy.
AB  - OBJECTIVE: Major depressive disorder (MDD) is associated with low-grade
      inflammation, and it is considered a risk factor for coronary artery disease
      (CAD). CD40 ligand (CD40L) plays an important role in inflammation, platelet
      activation, and clotting system activation. We investigated soluble CD40L
      (sCD40L) expression in MDD and assessed whether it may represent a molecular
      mechanism that links inflammation and a prothrombotic state and whether this
      condition may be modified by selective serotonin reuptake inhibitor (SSRI)
      therapy. METHOD: Levels of sCD40L, interleukin-1beta (IL-1beta), interleukin-6
      (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble P-selectin (sP
      selectin), activated factor VII (FVIIa), and prothrombin fragment 1+2 (F1+2) were
      measured in 46 drug-naive, first-episode MDD patients without conventional CAD
      risk factors and in 46 matched healthy controls. Participants were screened
      between March 2002 and November 2005. Twenty of the 46 MDD patients were then
      randomly assigned to either sertraline 100 mg/day (N = 10) or citalopram 20
      mg/day (N = 10); the aforementioned variables were measured at baseline and after
      6 weeks of treatment. RESULTS: Compared with control subjects, MDD patients had
      higher baseline levels of sCD40L, IL-1beta, IL-6, TNF-alpha, sP-selectin, FVIIa,
      and F1+2. In the clinical group, sCD40L levels, HAM-D total scores, and
      proinflammatory markers were strongly intercorrelated. In contrast, there were no
      significant correlations in the control group. Mood improvement achieved with
      SSRI therapy was associated with significant reduction in sCD40L, proinflammatory
      markers, and prothrombotic markers expression. (All p values < .0001.)
      CONCLUSIONS: This pilot study shows that CD40/ CD40L pathway up-regulation in MDD
      patients relates increased levels of sCD40L to a prothrombotic state and,
      preliminarily, indicates that SSRI therapy may significantly reduce sCD40L and
      CD40L levels associated with proinflammatory and prothrombotic states.

PMID- 17196055
TI  - Olanzapine versus risperidone in the treatment of manic or mixed States in
      bipolar I disorder: a randomized, double-blind trial.
AB  - OBJECTIVE: To compare olanzapine and risperidone in the treatment of nonpsychotic
      acute manic or mixed episodes. METHOD: This 3-week, randomized, controlled,
      double-blind, parallel multicenter study compared olanzapine (5-20 mg/day; N =
      165) and risperidone (1-6 mg/day; N = 164) among hospital inpatients who met DSM
      IV criteria for bipolar I disorder, manic or mixed episode, without psychotic
      features. The study was conducted at 30 sites in the United States between July
      2001 and June 2002. The primary outcome measure was the mean change in the Young
      Mania Rating Scale (YMRS) total score. Secondary measures included the 21-item
      Hamilton Rating Scale for Depression (HAM-D-21), the Montgomery-Asberg Depression
      Rating Scale (MADRS), the Clinical Global Impressions-Bipolar Version (CGI-BP)
      severity of illness scale, and the Cognitive Test for Delirium (CTD). Quality of
      life (Short Form Health Survey [SF-12]), psychological well-being (Psychological
      General Well-Being [PGWB] inventory), and sexual functioning were also compared.
      RESULTS: Mean modal doses for olanzapine and risperidone were 14.7 mg/day and 3.9
      mg/day, respectively. Between treatments, there was no difference in mean change
      in the YMRS, MADRS, CTD, PGWB, or SF-12 measures or in remission or response
      rates. Significantly more olanzapine-treated patients completed the study
      compared with risperidone patients (78.7% vs. 67.0%; p = .019). Olanzapine
      treated patients had greater HAM-D-21 (p = .040) and CGI-BP (p = .026) score
      improvement across the study. Olanzapine-treated patients experienced greater
      elevations in liver function enzymes (p < .05) and increase in weight (2.5 kg vs.
      1.6 kg; p = .004), while risperidone-treated patients were more likely to
      experience prolactin elevation (51.73 ng/mL vs. 8.23 ng/mL; p < .001) and sexual
      dysfunction (total score increase of 1.75 vs. 0.64; p = .049). CONCLUSION: Both
      olanzapine and risperidone treatment yielded similar improvements in mania. The
      olanzapine group had significantly greater improvements in secondary measures of
      severity and depressive symptoms and better study completion rates but
      experienced more weight gain.

PMID- 17196058
TI  - Escitalopram maintenance treatment for prevention of recurrent depression: a
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Major depressive disorder is a recurrent illness that often requires
      maintenance antidepressant treatment. Escitalopram is a selective serotonin
      reuptake inhibitor (SSRI) that has shown efficacy in both acute and continuation
      treatment of major depressive disorder. The current trial examined the efficacy
      of maintenance escitalopram treatment in preventing depression recurrence in
      patients who responded to acute SSRI therapy. METHOD: Patients with recurrent DSM
      IV-defined major depressive disorder (>or= 2 previous episodes; baseline
      Montgomery-Asberg Depression Rating Scale [MADRS] score >or= 22) who had
      responded (MADRS score <or= 12) to acute open-label treatment (8 weeks) with 1 of
      4 SSRIs (fluoxetine, sertraline, paroxetine, or citalopram) received open-label,
      flexible-dose continuation treatment (16 weeks) with escitalopram (10-20 mg/day).
      At the end of continuation treatment, patients maintaining response criteria were
      randomly assigned to 52 weeks of double-blind, fixed-dose maintenance treatment
      with escitalopram (10 or 20 mg/day) or placebo. Recurrence was defined as a MADRS
      score >or= 22 or insufficient therapeutic response during the double-blind phase.
      The study was conducted between October 16, 2000, and February 4, 2003. RESULTS:
      A total of 234 patients who responded to acute open-label treatment with 1 of 4
      SSRIs received at least 1 dose of open-label escitalopram continuation treatment.
      Of 164 patients who completed escitalopram continuation treatment, 139 were
      randomly assigned to double-blind maintenance treatment with escitalopram (N =
      73) or placebo (N = 66). Mean baseline MADRS scores at the start of the
      maintenance phase were < 5 for both the placebo- and escitalopram-treatment
      groups. Time to recurrence was significantly longer in patients who received
      maintenance treatment with escitalopram compared with patients switched to
      placebo (hazard ratio = 0.26, 95% CI = 0.13 to 0.52, p < .001). Long-term
      escitalopram treatment was well tolerated. CONCLUSION: Maintenance treatment with
      escitalopram was well tolerated and significantly reduced the risk for recurrence
      of depression. Patients with few residual symptoms following continuation
      treatment with escitalopram experienced a high rate of depression recurrence when
      switched to placebo, demonstrating the need for maintenance therapy of recurrent
      major depressive disorder beyond 4 to 6 months of initial symptom resolution even
      if few residual symptoms are present.

PMID- 17196059
TI  - Antidepressants and driving ability: results from a clinical study.
AB  - OBJECTIVE: Psychomotor disturbances can frequently be found in depressed patients
      and may have an important influence on the ability to drive. Additionally,
      effects of sedation, as seen with some antidepressants, probably impair driving
      performance. The present study was designed to evaluate the effects of
      antidepressant monotherapy on psychomotor functions related to car-driving skills
      in depressive patients in a routine clinical setting. METHOD: Inpatients (N =
      100) who met the ICD-10 and DSM-IV criteria for major depressive disorder were
      tested under steady-state plasma level conditions prior to being discharged to
      out-patient treatment. The study ran from January 2004 through March 2005. All
      patients participated voluntarily and gave informed consent. According to the
      German guidelines for road and traffic safety, data were collected with the
      computerized Act & React Testsystem ART-90 and the Wiener Testsystem, measuring
      visual perception, reaction time, selective attention, vigilance, and stress
      tolerance. Psychopathologic symptoms were rated with the Hamilton Rating Scale
      for Depression. RESULTS: Before discharge to outpatient treatment, 24% of the
      patients tested were without clinically relevant psychomotor disturbances. In 60%
      of the cases, mild to moderate impairments could be seen, and about 16% of the
      patients were considered as severely impaired in psychomotor functions related to
      car-driving abilities. Data show that patients treated with selective serotonin
      reuptake inhibitors (SSRIs) or the noradrenergic and specific serotonergic
      antidepressant (NaSSA) mirtazapine had an altogether better test performance in
      comparison with patients receiving tricyclic antidepressants (TCAs). Differences
      were most pronounced in measures of reactivity, stress tolerance, and selective
      attention. Statistically significant differences between patients treated with
      TCAs or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine could
      not be found. Among the newer antidepressants there is an advantage for patients
      treated with mirtazapine, especially in tasks with high multi-channel perception
      and output demands. CONCLUSION: About 16% of depressive patients discharged from
      hospital to outpatient treatment must be considered unfit to drive. In 60% of the
      cases, patients performed at a questionable level of fitness for driving, and it
      seems justified to counsel patients individually, taking into account
      compensational factors. Data point to an advantage for patients treated with
      SSRIs or mirtazapine when compared with TCAs or venlafaxine. However, causal
      relationships cannot be drawn from our data.

PMID- 17196060
TI  - A 100-year update on Alzheimer's disease and related disorders.

PMID- 17196061
TI  - Alzheimer's disease a century later.
AB  - OBJECTIVE: To provide a current survey of the clinical and pathologic features,
      known genetic and suggested pathogenic contributions, diagnosis, and treatment of
      Alzheimer's disease (AD) and related forms of dementia. DATA SOURCES: PubMed was
      searched for specific indexing terms identified by the authors as relevant to the
      topic. Also included were diagnostic and consensus criteria and classic
      references long standing in the Alzheimer's disease literature. DATA SYNTHESIS:
      AD is the most common form of disabling cognitive impairment in older persons,
      and its prevalence is rapidly growing as people live to older ages. Clinically,
      the disorder is characterized by a gradual but progressive decline in memory and
      other cognitive domains and the frequent occurrence of noncognitive behavioral
      symptoms. Neuropathologically, the cardinal features of AD include neuritic
      plaques, neuro-fibrillary tangles, and the loss of synapses and neurons. The
      clinical evaluation of AD includes a history and physical examination, laboratory
      tests, and structural brain imaging to exclude less common forms of dementia. The
      clinical management of AD includes medication and nonmedication strategies for
      addressing cognitive, behavioral, and other commonly associated symptoms of
      patients as well as lifestyle changes such as driving cessation and residential
      care. Genetic causes of familial Alzheimer's disease as well as genes that
      predispose to late-onset and sporadic Alzheimer's disease have led to greater
      understanding of the pathophysiology of the neurodegenerative process.
      CONCLUSIONS: While there has been great promise in the scientific understanding,
      early detection, and tracking of AD and in the discovery of promising disease
      slowing treatments, there remains an unmet urgent need to identify effective
      primary and secondary prevention therapies in order to avert a financially
      overwhelming public health problem.

PMID- 17196062
TI  - New developments in addiction treatment.

PMID- 17196063
TI  - Measurement-based psychiatry: definitions of response, remission, stability, and
      relapse in schizophrenia.

PMID- 17196064
TI  - Until death do us part.

PMID- 17196065
TI  - Diagnostic and therapeutic challenges in narcolepsy-related psychosis.

PMID- 17196066
TI  - Manic switch in a patient with treatment-resistant bipolar depression treated
      with modafinil.

PMID- 17196067
TI  - Beneficial effects of prazosin for visual hallucinations associated with chronic
      cocaine abuse.

PMID- 17196068
TI  - Tactile hallucinations associated with therapeutic doses of bupropion in 2
      patients.

PMID- 17196069
TI  - Fluoxetine-mirtazapine interaction may induce restless legs syndrome: report of 3
      cases from a clinical trial.

PMID- 17196070
TI  - Immediate switching from moclobemide to duloxetine may induce serotonin syndrome.

PMID- 17196072
TI  - Laser diffractometry as a technique for the rapid assessment of aerosol particle
      size from inhalers.
AB  - The rapid assessment of aerosols produced by medicinal inhalers is highly
      desirable from several standpoints, including the assurance of product quality,
      the development of new delivery systems, and the need to meet an increasing
      requirement by regulatory bodies for reliable in vitro performance data. Particle
      size analysis has traditionally been undertaken by cascade impactor on account of
      the direct assessment of active pharmaceutical ingredient(s) (APIs) that is
      possible by this method. However, laser diffractometry is less labor-intensive,
      more rapid, and can be a less invasive procedure. The technique provides
      meaningful results; as long as precautions are taken to validate that the
      measurements are an accurate reflection of the distribution of API mass as a
      function of particle or droplet size. We begin the review by examining the
      underlying theory of the laser diffraction method. After a brief description of
      current laser diffractometers used in inhaler measurements, we continue by
      examining the range of applications by inhaler class. We then examine the basis
      upon which inhaler measurements made by laser-diffractometry can be compared with
      equivalent particle size distribution data from compendial techniques. We
      conclude the assessment of the technique by developing guidelines for its valid
      application as a component of the range of in vitro methods that are available
      for inhaler performance assessment.

PMID- 17196073
TI  - Aerosol sampling methods in workplace and ambient environments.
AB  - Aerosols are emitted into the workplace atmosphere and the ambient environment
      through a variety of processes. Aerosol particles are known to have significant
      effects on both human health and the ambient environment. For this reason,
      monitoring aerosol concentrations in the atmosphere by aerosol sampling is
      undertaken in workplace and ambient environments. A wide range of aerosol
      sampling methods using different collection mechanisms has been used for
      collecting representative aerosol samples using either a collecting or sensing
      medium. This paper shows the existing and commonly used aerosol sampling methods
      based on aerosol collection and real-time measurements. The method of choice for
      aerosol sampling will ultimately depend on a variety of factors, such as purpose
      of sampling, type of aerosol, analysis requirements, and available budget.

PMID- 17196074
TI  - Effect of dry powder inhaler resistance on the inspiratory flow rates and volumes
      of cystic fibrosis patients of six years and older.
AB  - Several inhaled drugs for use by cystic fibrosis (CF) patients are formulated for
      nebulizer use only. This therapy is time consuming and includes the risk of
      contamination of the nebulizers. Dry powder inhalers (DPI) can be an attractive
      alternative for CF drugs. Inhaled flow rate and volume, and the device resistance
      are important determinants for optimal dispersion of drug from a DPI. It is
      important to understand how these variables interact in the CF population in
      order to properly design a new DPI formulation targeted for these patients. The
      objective of this study was to assess the inspiratory variables of a
      representative population of CF subjects 6 years and older with varying degrees
      of lung disease while inhaling through resistances that simulate DPI devices.
      Ninety-six stable CF patients were enrolled, ages 6-54 years, FEV(1) 19-126%
      predicted. Subjects inhaled forcefully through four different resistances (0.019,
      0.024, 0.038, and 0.048 kP(0.5)/LPM, respectively), while inspiratory time
      (IT(DPI)), peak inspiratory flow (PIF(DPI)), and volumes (V(DPI)) were measured.
      For any resistance, inspired V(DPI) increased with the older age groups; PIF(DPI)
      was similar between adults and adolescents but lower in the children. Subjects
      with lower FEV(1) had lower V(DPI) and PIF(DPI). As resistance increased,
      PIF(DPI) decreased, IT(DPI) increased, with no significant change in V(DPI). At
      the lowest resistance mean PIF(DPI) was 105 LPM (range 45-163) for all patients;
      112 LPM (range 75-163) in adults; and 89 LPM (45-126) in children. Mean inspired
      V(DPI) was 1.75 L for all patients; 2.2 L (0.8-3.7) in adults; and 1.2 L (0.5
      1.8) in children. At the lowest resistance a minimal flow rate of 30, 45, and 60
      LPM was attained in 100%, 99%, and 96% of all patients. Volumes of 1.0, 1.5, and
      2.0 L were attained by 85%, 57%, and 30% of the patients. At the highest
      resistance mean PIF(DPI) was 52 LPM (range 26-70) for all patients; 55 LPM (40
      70) in adults; and 47 LPM (26-62) in children. Mean inspired V(DPI) was 1.5 L in
      all patients; 1.9 L (0.9-3.5) in adults and 1.1 L (0.5-2.3) in children. At the
      highest resistance, a minimal flow rate of 30, 45, and 60 LPM was attained in
      99%, 80%, and 22% of all patients. Volumes of 1, 1.5, and 2 L were attained in
      84%, 45%, and 23% of the patients. We defined ranges for inspiratory variables in
      a diverse CF population for a range of device resistances that bracket those of
      current DPIs. The recorded inspiratory patterns can be used on the bench to
      design and test new dry powder formulations and devices to target the largest
      proportion of the CF population.

PMID- 17196075
TI  - In vitro comparison of two delivery devices for administering formoterol: Foradil
      P and formoterol ratiopharm single-dose capsule inhaler.
AB  - Formoterol, a long-acting beta (2)-agonist with a rapid onset of bronchodilation,
      is available in various delivery devices. However, differences in the size and
      uniformity of drug particles generated by different devices may result in
      variable clinical effects. The present study compared in vitro the aerodynamic
      particle size distribution, emitted dose and device resistance of formoterol
      delivered via Foradil Aerolizer (Foradil P) with those a non-proprietary single
      dose capsule inhaler (ratiopharm), using an 8-stage Andersen Cascade Impactor set
      at a flow of 60 L/min. Relative to the formoterol ratiopharm capsule inhaler,
      Foradil Aerolizer produced particles with a smaller mass median aerodynamic
      diameter (3.5 vs. 4.1 microm, p = 0.018) and a smaller measured particle diameter
      distribution (geometric standard deviation 2.2 vs. 2.5, p = 0.048). The Foradil
      Aerolizer produced a 44% higher fine particle dose than the single-dose capsule
      inhaler (2.6 vs. 1.8 microg, p = 0.0001). Although the single-dose capsule
      inhaler produced a higher total emitted dose than that from Foradil Aerolizer
      (11.2 vs. 10.0 microg, p = 0.155, not significant), the respirable fraction from
      Foradil Aerolizer was 58% higher (25.7 vs. 16.3%, p = 2 x 10(8)). Both devices
      had a similarly low airflow resistance. These relative particle size profiles
      suggest that the Aerolizer may provide a more clinically effective delivery of
      formoterol to the lungs at the high inspiratory flows such as are typically
      achieved using this device.

PMID- 17196076
TI  - Degree of throat deposition can explain the variability in lung deposition of
      inhaled drugs.
AB  - Inhalation is a mainstay for treatment of asthma, and lung deposition can be seen
      as a surrogate marker for the ensuing clinical effects. Not only absolute lung
      deposition, but also its variability is of interest, as it indicates the range of
      expected lung deposition in an individual patient when prescribing the drug and
      the expected day-to-day variability when using it. A literature survey found 71
      studies with relevant information on lung deposition and its variability. Further
      characteristics of the studies, such as if the subjects were healthy or
      asthmatics, adults or children, and what device that was used, were noted. In
      all, 187 data points were included. Variability in lung deposition was depicted
      as a function of mean lung deposition; for the entire data set and for subsets
      thereof. Independent of device type or subject category high lung deposition was
      associated with low relative variability and vice versa. Using a published throat
      deposition model, the observed correlation of lung deposition variability to mean
      lung deposition could be explained as being determined largely by the extent of
      and variability in throat deposition. We hypothesize that throat deposition is
      the major determinant for lung deposition of an inhaled aerosol, and its absolute
      variability will largely be determined by the absolute variability in throat
      deposition. The relative variability in lung deposition will therefore tend to be
      high for low lung deposition and low for high lung deposition. Consequently, low
      relative variability in lung deposition can only be attained if high lung
      deposition is achieved.

PMID- 17196077
TI  - Nebulized drug admixtures: effect on aerosol characteristics and albuterol
      output.
AB  - Although not recommended, co-administration of drugs separately prescribed for
      nebulization is done in real life. The impact of this practice on drug output and
      aerosol characteristics is poorly understood. We studied the effect of drug
      admixtures (DA) on aerosol characteristics and drug output of nebulized albuterol
      delivered by a continuous output (CONT) and a breath enhanced nebulizer (BEN).
      Albuterol was nebulized alone (ALB) and combined with cromolyn sodium (A+CRO),
      ipratropium bromide (A+IB), tobramycin (A+TOB), flunisolide (A+FLU), and n
      acetylcysteine (A+NAC). A BEN (PARI LC Plus) and a CONT (Hudson T UP-DRAFT II)
      were tested at 8 liters per minute (Lpm) for 2 and 5 min, respectively. Albuterol
      output and aerosol characteristics were determined by impaction and chemical
      analysis. Mass median aerodynamic diameter (MMAD; microm) A+CRO reduced MMAD from
      2.57 (ALB) to 1.29 with CONT. A+FLU increased MMAD from 2.71 (ALB) to 3.40 with
      BEN. Geometric standard deviation (GSD) A+CRO increased GSD from 2.66 (ALB) to
      3.36 with CONT. GSD was 2.33 for ALB and was not changed by DA with BEN. BEN
      generated a smaller and less heterodisperse aerosol than CONT. Respirable
      fraction (RF%) was 74% for ALB and was not changed by DA with CON. A+TOB and
      A+FLU decreased RF% from 75%, to 70% and 67% (respectively) with BEN. Respirable
      mass (RM; microg) for ALB was 935 and was not changed by DA with CONT. A+IB and
      A+FLU increased RM from 917 (ALB) to 1172 and 1240, respectively, with BEN. Co
      nebulization of albuterol with other drugs can affect its output and aerosol
      characteristics. In vivo data is needed to asses the clinical implications of our
      findings.

PMID- 17196078
TI  - Factors affecting magnetic retention of particles in the upper airways: an in
      vitro and ex vivo study.
AB  - This paper presents the results of experiments using an in vitro model and an ex
      vivo animal model (Rana catesbeiana) to study magnetic particle retention in the
      conducting airways, specifically the trachea and bronchi. The purpose of these
      experiments was to determine the significant factors for retention of magnetic
      particles deposited from an aerosol at the airway surface using a magnetic field.
      The results indicate that the apparent viscosity of the mucus layer at low shear
      rates is the most significant obstacle to particle retention. The results also
      show that particle size and aggregation play major roles in particle retention.
      The mucus transport rate, unlike the effect of fluid velocity in intravenous
      applications, did not appear to be a determining factor for particle retention.
      It was also found that a suitably designed magnetic system, aside from having a
      high intensity, needs to exert a strong radial field to promote particle
      aggregation. The findings suggest that one possible approach to magnetic particle
      retention could be delivery of a mucolytic agent along with the drug particles.
      This study provides the fundamentals needed for development of a targeted
      magnetic drug delivery system for inhaled therapeutic aerosol particles.

PMID- 17196079
TI  - Validity of in vitro tests on aqueous spray pumps as surrogates for nasal
      deposition, absorption, and biologic response.
AB  - This research investigated the impact of the full range of in vitro spray
      characterization tests described in the FDA Draft Bioequivalence Guidance on
      nasal deposition pattern, pharmacokinetics, and biological response to nicotine
      administered by two aqueous nasal spray pumps in human volunteers. Nicotine was
      selected as a model drug (even though it is not locally acting) based on its
      ability to alter cardiac function and available plasma assay. Significant
      differences in pump performance-including mean volume diameters, spray angle,
      spray width, and ovality ratios-were observed between the two pumps. There were
      no significant differences in deposition pattern, or pharmacokinetic or
      pharmacodynamic response to the nasally administered nicotine. Although there
      were statistical differences in the in vitro tests between the two pumps, these
      differences did not result in significant alterations in the site of droplet
      deposition within the nose, the rate and extent of nicotine absorption, or the
      physiologic response it induced. These results suggest that current measures of
      in vitro performance, particularly spray angle and spray pattern (ovality), may
      not be clinically relevant. Additional research is needed to define what spray
      pump characteristics are likely to produce differences in deposition pattern and
      drug response.

PMID- 17196080
TI  - Lung deposition of mannitol powder aerosol in healthy subjects.
AB  - Mannitol as a dry powder aerosol is used for bronchoprovocation testing and to
      enhance mucus clearance in people with excessive airway secretions. The dose and
      distribution of the deposited aerosol in the lung was investigated using fast
      single photon emission tomography (SPECT) imaging. Mannitol powder (3 microm
      particle size) was produced by spray drying and radiolabeled with (99m)Tc-DTPA.
      Approximately 60 mg of radiolabeled mannitol (containing 52-68 MBq of (99m)Tc
      DTPA) was administered to 10 healthy subjects using the Inhalator dry powder
      inhaler (DPI), and SPECT images (1 min each) were collected. Thirteen percent to
      31% of the dose of mannitol loaded in the inhaler deposited in the lungs and the
      deposited dose correlated positively with the peak inhalation air flow. The
      regional aerosol lung distribution, as expressed by the penetration index (i.e.,
      ratio of peripheral to central deposition in the lung) varied from 0.31 to 0.88,
      which however showed no dependency on any flow parameters. The variation in
      response to the same dose of mannitol within the asthmatic population may in part
      be explained by these findings.

PMID- 17196081
TI  - Administration of aerosolized drugs to infants by a hood: a three-dimensional
      numerical study.
AB  - Using a hood for aerosol delivery to infants was found to be effective and user
      friendly compared to the commonly used face mask. The currently available hood
      design has an even greater potential in terms of efficiency, and a numerical
      simulation can serve as a tool for its optimization. The present study describes
      the development and utilization of a numerical simulation for studying the
      transport and fate of the aerosol particles and the carrier gas within a three
      dimensional realistic representation of the hood and the infant's head. The study
      further incorporates realistic breathing patterns, with a longer expiration phase
      than an inspiration phase. Both nose and mouth breathing are simulated. While the
      base case assumes that the funnel that delivers the aerosol within the hood is
      perpendicular to the infant's face, more realistic scenarios include a funnel
      that is slanted with respect to the infant face, the infant's head taking a
      general position with respect to the funnel, and the funnel and the head being
      both tilted. A good agreement is found between computation and experimental
      results. As expected, the most efficient drug delivery, 18%, is achieved when the
      funnel is normal to the infant's face. The quantitative evaluation of different
      scenarios presented in this work increases the knowledge of physicians, nurses,
      and parents regarding the efficacy of the treatment, in terms of the actual
      amount of drug inhaled under various modes of function of the device.

PMID- 17196082
TI  - Application of heated inlet extensions to the TSI 3306/3321 system: comparison
      with the Andersen cascade impactor and next generation impactor.
AB  - Pharmaceutical aerosol size distribution analysis based on multi-stage inertial
      impaction is well accepted, though laborious. The TSI 3306 Impactor Inlet/3321
      time-of-flight (TOF) Aerodynamic Particle Size Analyzer (APS) has been evaluated
      for its ease of use and potential for time savings during product development.
      However, instrument inlet modifications may be necessary for increased
      correlation with equivalent measurements obtained by inertial impaction following
      pharmacopeial methods. A heated inlet extension tube was located between the
      USP/Ph.Eur. throat and the Single-Stage Impactor (SSI) to promote evaporation of
      residual ethanol from aerosol droplets, generated from two formulations
      containing ethanol as semi-volatile solubilizer (8 and 20% w/w) for the active
      pharmaceutical ingredient. As temperature and extension length increased, the SSI
      measured fine particle fraction (aerosol < 4.7 microm aerodynamic diameter) also
      increased, for the aerosols used in this study. These values correlated quite
      closely with equivalent measures made by multi-stage cascade impactor equipped
      with the same throat. Particle size distribution profiles measured with the APS
      for either formulation did not significantly change utilizing the heated
      extensions, suggesting that ethanol evaporation was largely complete at any
      condition by the time the aerosol entered the measurement zone of the TOF
      analyzer. The addition of a heated inlet extension may be useful to facilitate
      evaporation of residual semi-volatile species, especially when an agreement of
      APS-derived particle size mass distribution data from the SSI with multi-stage
      cascade impactors is desired. However, complete evaporation of the semi-volatile
      species may not be necessary for SSI-generated mass distribution to match
      conventionally used cascade impactors.

PMID- 17196083
TI  - Dosimetry counts: molecular hypersensitivity may not drive pulmonary
      hyperresponsiveness.
AB  - Airway hyperresponsiveness is one measure of allergic asthma. One such test, the
      methacholine challenge, uses an inhaled aerosol to induce changes in resistance
      to breathing. The test is also used to test hyperresponsiveness in rodent models
      of asthma. For two varieties of mice, the B6C3F1 and the Balb/c, exposure to
      aerosolized methacholine demonstrates that the Balb/c is 12x more responsive
      based on the concentration of methacholine in the solution used to produce the
      inhaled aerosol (the normally accepted dose-metric). Here we show that the 12x
      difference in exposure disappears when measurements of airway dimensions of
      generations 1-6 are used first to calculate deposited mass of methacholine; and
      second to account for the physiology of airway constriction and pressure drop.
      These observations in mice provide one explanation of how some hyperresponsive
      subjects can have no underlying molecular sensitivity; and how constriction in
      the upper airways can have greater impact on breathing than constriction of
      airway generations 6-16.

PMID- 17196084
TI  - Analytical technique to recover the third dimension in planar imaging of inhaled
      aerosols: (1) impact on spatial quantification.
AB  - An analytical algorithm is described for converting planar scintigraphic images
      of aerosol distributions in the lungs to an equivalent three-dimensional (3D)
      representation. The recovery of volumetric information should benefit regional
      quantification. The technique has been validated using simulated planar images of
      eleven known aerosol distributions in ten realistic lungs. Global and regional 3D
      parameters, such as the total activity deposition (A), the penetration index (PI)
      and the relative penetration index (rPI), were quantified on the planar images
      and on their 3D representation. Random and systematic errors of the estimation
      were measured. Finally, the performance of planar imaging was compared with that
      of single-photon emission computed tomography (SPECT). SPECT images were
      simulated for the same aerosol distributions in the same subjects and quantified
      for A, PI, and rPI. The systematic errors in A, PI and rPI obtained from planar
      imaging were 8.9%, 64.8%, and 54.1%, respectively, using the two-dimensional (2D)
      analysis; they improved significantly to 4.4%, 19.0%, and 25.5% with the 3D
      analysis (p < 0.01). The corresponding values for SPECT were 5.2%, 9.8%, and
      15.7%, significantly better for PI and rPI (p < 0.01). The random errors of A
      were similar for all techniques being about 5%; those of PI and rPI measurements
      were significantly higher for planar imaging (<or=14%) than SPECT (<or=8%). In
      conclusion, 3D spatial parameters can be derived from planar imaging that are
      significantly more accurate in characterizing different aerosol depositions than
      their 2D counterpart. However, the errors remain significantly higher than with
      SPECT.

PMID- 17196085
TI  - Aerosol drug delivery with helium oxygen gas mixtures to the human lungs.

PMID- 17196087
TI  - An astonishing experiment.

PMID- 17196088
TI  - Mutation and cloning efficiency.

PMID- 17196089
TI  - Chemically assisted handmade enucleation of porcine oocytes.
AB  - The purpose of our work was to find an efficient and reliable chemically assisted
      procedure for enucleation of porcine oocytes connected to the handmade cloning
      (HMC) technique without the potentially harmful chromatin staining and
      ultraviolet (UV) irradiation for cytoplast selection. After 41-42 h in vitro
      maturation, porcine oocytes were incubated with 0.4 microg/mL demecolcine for 45
      min. Subsequently, the cumulus cells were removed and zonae pellucidae were
      partially digested. Oocytes with extrusion cones or oocytes only with polar body
      (PB) were subjected to oriented bisection. Less than half of the cytoplasm with
      the extrusion cone or adjacent to the PB was removed with a microblade. The
      remaining putative cytoplasts, containing the major part of the cytoplasm, were
      used as recipients for reconstruction with porcine fetal fibroblasts as nuclear
      donors. The overall efficiency achieved with chemically assisted enucleation was
      higher compared to oriented bisection without demecolcine incubation (90 +/- 3%
      vs. 81 +/- 4%, respectively; mean +/- absolute deviation [AD]). Reconstructed and
      activated embryos were cultured in vitro for 7 days. Fusion, cleavage and
      blastocyst rates were 87 +/- 7%, 97 +/- 6%, and 28 +/- 9%, respectively. These
      rates are at least as good as those achieved with normal HMC (81 +/- 4%, 87 +/-
      8%, and 21 +/- 9%, respectively). For traditional, micromanipulator-based
      cloning, fusion and blastocyst rates were similar (81 +/- 10% and 21 +/- 6%,
      respectively), but the cleavage rate was lower (69 +/- 9%). In conclusion,
      chemically assisted handmade enucleation seems to be a simpler and potentially
      superior alternative to more conventional methods used for somatic cell nuclear
      transfer in pigs.

PMID- 17196090
TI  - Dynamic changes in microtubules and early development of reconstructed embryos
      after somatic cell nuclear transfer in a non-human primate.
AB  - In order to improve somatic cell nuclear transfer (SCNT) efficiency and to
      understand cellular changes in SCNT, the dynamic changes in microtubules/DNA and
      early development of SCNT embryos with single or multiple pronuclei were
      investigated, along with activation timing on efficiency of SCNT, were studied in
      the Cynomolgus monkey. The confocal images showed that microtubules assembled
      around condensed DNA at 1h after cell injection; normal or abnormal reconstructed
      spindle formed at 2 h after cell injection; and reconstructed spindle separated
      at 2 h after activation. The results of nuclear formation showed that 61.3% of
      the reconstructed embryos did not form pronuclei; 19.3% formed a single nucleus,
      and 11.9% and 7.5% formed two and more than two reconstructed pronuclei,
      respectively. The cleavage and 8-cell development rates of SCNT embryos with
      pronuclei were significantly higher than those without pronuclei, but there was
      no difference in development rates among NT embryos with single, two and more
      then two pronuclei. Activation at 2 h after cell injection yielded more embryos
      with pronuclei and yielded 8-cell NT embryos more reliably than did activation at
      3-4 h. In conclusion, microtubules assembled around condensed DNA at 1-2 h after
      cell injection, and formed a spindle at 2 h after SCNT, which separated at 2 h
      after activation; early development was affected by activation time, but no
      different between single and multiple pronuclei.

PMID- 17196091
TI  - Molecular analysis of maturation processes by protein and phosphoprotein
      profiling during in vitro maturation of bovine oocytes: a proteomic approach.
AB  - Cellular maturation and differentiation processes are accompanied by the
      expression of specific proteins. Especially in oocytes, there is no reliable
      strict linear correlation between mRNA levels and the abundance of proteins.
      Furthermore, the activity of proteins is modulated by specific kinases and
      phosphatases which control cellular processes like cellular growth,
      differentiation, cell cycle and meiosis. During the meiotic maturation of
      oocytes, the activation of protein kinases, namely of the MPF and MAPK play a
      predominant role. Therefore, the present study was performed to analyze meiotic
      maturation at a molecular level, concerning alterations of the proteom and
      phosphoproteom during IVM. Using a proteomic approach by combining two
      dimensional gel electrophoresis followed by selective protein and phosphoprotein
      staining and mass spectrometry, we identified proteins which were differentially
      expressed and/or phosphorylated during IVM. Furthermore, we used the MPF
      inhibitor butyrolactone I, to reveal new molecular effects which are potentially
      essential for successful maturation. The results show that approximately 550
      protein spots could be visualized by the fluorescent dye Sypro ruby at any
      maturation stage (GV, M I, M II) investigated. From GV stage to M II, ProQ
      diamond staining indicate in GV 30%, in M I 50%, and in M II 45% of the spots
      were phosphorylated. The Identity of 40 spots could be established. These
      proteins belong to different families, for example, cytoskeleton, molecular
      chaperons, redox, energy and metabolism related proteins, nucleic acid binding
      proteins, cell cycle regulators, and protein kinases. Four of them were
      differentially expressed (alteration higher than factor 2) during IVM, namely
      tubulin beta-chain, cyclin E(2), protein disulfide isomerase and one of two
      different forms of peroxiredoxin 2. Seven proteins were differentially stained by
      ProQ diamond, indicating a differential phosphorylation. These are tubulin beta
      chain, beta-actin, cyclin E(2), aldose reductase and UMP-synthase, protein
      disulfide isomerase 2, and peroxiredoxin 2. Furthermore, the results indicate
      that the phosphorylation of at least peroxiredoxin 2 respond to BL I treatment.
      This indicates that its phosphorylation is under the control of MPF or MAPK. In
      summary these results indicates that the reduction of cyclin Eexpression and the
      (partially) inactivation of peroxiredoxin 2 by phosphorylation, hence alterations
      in the peroxide levels which can mediate signal transduction are essential
      components for successful maturation.

PMID- 17196092
TI  - Oocyte spontaneous activation in different rat strains.
AB  - Oocyte spontaneous activation (OSA) has been reported to occur during in vitro
      culture of ovulated rat oocytes. The objective of this study was to compare the
      rate of oocyte spontaneous activation and the level of maturation promoting
      factor (MPF) activity in oocytes from different strains. Twelve strains were
      selected from two commercial sources. Females were superovulated and oocytes
      collected 17 h after hCG injection. Denuded oocytes were cultured in M16 medium
      under oil at 37 degrees C and 5% CO(2) in air. The proportion of activated
      oocytes was determined after 6 h of in vitro culture. Data were compared by
      analysis of variance (ANOVA), considering each animal as an experimental unit.
      MPF activity was determined in oocytes from the different strains at 0, 1.5, and
      3 h after oocyte collection. The log ratio of the MPF activity at 1.5 and 3 h
      relative to 0 hours for each animal was analyzed by ANOVA. While significant (p <
      0.01) differences were observed between strains in the rate of OSA, there were no
      differences between strains in the level of MPF during the time points measured
      (p > 0.3).

PMID- 17196093
TI  - Birth of cloned pigs from zona-free nuclear transfer blastocysts developed in
      vitro before transfer.
AB  - The objective of this work was to obtain cloned pig offspring by uterine transfer
      of blastocysts produced by zona-free manipulation. We started by defining the
      most suitable culture media for growing pig nuclear transfer embryos produced by
      zona-free micromanipulation comparing NCSU-23aa with Synthetic Oviduct Fluid
      (SOFaa) and with in vivo culture in the sheep oviduct. We found that
      parthenogenetic development to day 7 blastocyst in NCSU-23aa and sheep oviduct
      was significantly superior as compared to SOFaa (61.8%, 64% and 42.4
      respectively) although blastocyst cell number was higher in the latter.
      Interestingly, when we compared the two media for the culture of nuclear transfer
      (NT) embryos derived from 3 different donor cell lines, we observed lower rates
      of development with NCSU-23aa (from 24.5% to 32.4%) while with SOFaa the
      development was significantly higher for two donor cell lines as compared to the
      third (44.4%, 48.9% and 20.6% respectively). A total of 244 blastocysts grown in
      SOFaa were transferred in four synchronized sows on day 5 or 6 of development.
      Two recipients farrowed 6 and 8 piglets corresponding to an efficiency of
      development to term of 8% and 16% of the transferred embryos respectively. Eleven
      pigs are now 10 month of age and those that have reached puberty have been proven
      to be fertile. Finally, this is the first report on the production of cloned pigs
      derived from the transfer of NT embryos at the blastocyst stage.

PMID- 17196094
TI  - Zygotically activated genes are suppressed in mouse nuclear transferred embryos.
AB  - Mammalian oocytes have the ability to confer totipotency to terminally
      differentiated somatic cell nuclei. Viable cloned animals have been produced by
      somatic cell nuclear transfer (NT) into oocytes in many mammalian species
      including mouse. However, the success rates of the production were quite low in
      all species. Many studies have measured differences in gene expression between NT
      and fertilized embryos in relatively advanced stages of development such as pre-
      and post-natal stages or the blastocyst stage. In the present study, we compared
      gene expression patterns using differential display RT-PCR (DDRT-PCR) between the
      NT and IVF embryos at the 2-cell stage to detect some abnormalities affecting
      later development of NT embryos. Aberrant gene expression was detected in NT
      embryos compared with IVF embryos, and MuERV-L and Dnaja2 genes were down
      regulated and Inpp5b and Chst12 genes were up-regulated in the NT embryos.
      Further analysis showed that the expression of zygotically activated genes such
      as Interferon-gamma, Dub-1, Spz1, DD2106 (unknown gene), and DD2111 (unknown
      gene) were suppressed in NT embryos, suggesting that the cellular process
      involved in the nuclear reprogramming of somatic nucleus is not appropriately
      regulated.

PMID- 17196095
TI  - Telophase-stage host ooplasts support complete reprogramming of roscovitine
      treated somatic cell nuclei in cattle.
AB  - Nuclear-cytoplasmic incompatibilities are known to play a significant role in the
      developmental outcome of embryos produced by nuclear transfer, particularly when
      metaphase arrested oocytes are used as hosts for interphase donor nuclei. To
      further our understanding of how cell cycle coordination affects somatic cell
      cloning, somatic cells at different stages of the cell cycle were fused to host
      oocytes either before (metaphase II, M-II) or after (telophase II, T-II)
      activation. To obtain cells at different stages of the cell cycle, fetal
      fibroblast (FF) and granulosa cells (GC) were treated with roscovitine, an
      inhibitor of cyclin-dependent kinases (CDKs) resulting in a large percentage of
      cells in S/G(2)-phase. In contrast to the M-II group, which did better with
      confluent cells, embryos reconstructed with T-II cytoplasts resulted in higher
      rates of blastocyst formation when fused to cells recovered at 16-24 h after
      passage. Embryos reconstructed with FF treated with roscovitine and T-II
      cytoplasts (Rosc/T-II) resulted in similar blastocyst rate compared to those
      produced with confluent cells and M-II cytoplasts (Conf/M-II). Transfer of
      blastocysts to surrogate heifers resulted pregnancies and birth of healthy calves
      from Rosc/T-II and Conf/M-II reconstructed embryos. These results indicate that,
      when combined with nuclear donor cells at specific cell cycle stages, M-II and T
      II bovine oocytes are similarly effective in supporting the reprogramming of
      somatic cell nuclei.

PMID- 17196096
TI  - Variations in humanized and defined culture conditions supporting derivation of
      new human embryonic stem cell lines.
AB  - The evolution of "humanized" (i.e., free of animal sourced reagents) and
      ultimately chemically defined culture systems for human embryo stem cell (hESC)
      isolation and culture is of importance to improving their efficacy and safety in
      research and therapeutic applications. This can be achieved by integration of a
      multitude of individual approaches to replace or eliminate specific animal
      sourced reagents into a single comprehensive protocol. In the present study our
      objective was to integrate strategies obviating reliance on some of the most
      poorly defined and path-critical factors associated with hESC derivation, namely
      the use of animal immune compliment to isolate embryo inner cell mass, and animal
      sourced serum products and feeder cells to sustain hESC growth and attachment. As
      a result we report the derivation of six new hESC lines isolated by outgrowth
      from whole blastocysts on an extracellular matrix substrate of purified human
      laminin (Ln) with transitional reliance on mitotically inactivated human
      fibroblast (HDF) feeder cells. With this integrated system hESC lines were
      isolated using either HDF conditioned medium supplemented with a bovine-sourced
      serum replacement (bSRM), or a defined serum-free medium (SFM) containing only
      human sourced and recombinant protein. Further, outgrowth of embryonic cells from
      whole blastocysts in both media could be achieved for up to 1 week without
      reliance on feeder cells. All variant conditions sustained undifferentiated cell
      status, a stable karyotype and the potential to form cells representative of all
      three germinal lineages in vitro and in vivo, when transitioned off of feeders
      onto Laminin or Matrigel. Our study thus demonstrates the capacity to integrate
      derivation strategies eliminating a requirement for animal immune compliment and
      serum products, with a transitional requirement for human feeder cells. This
      represents another sequential step in the generation of therapeutic grade stem
      cells with reduced risk of zoonotic pathogen transmission.

PMID- 17196097
TI  - A novel statistical method to estimate the effective SNP size in vertebrate
      genomes and categorized genomic regions.
AB  - BACKGROUND: The local environment of single nucleotide polymorphisms (SNPs)
      contains abundant genetic information for the study of mechanisms of mutation,
      genome evolution, and causes of diseases. Recent studies revealed that
      neighboring-nucleotide biases on SNPs were strong and the genome-wide bias
      patterns could be represented by a small subset of the total SNPs. It remains
      unsolved for the estimation of the effective SNP size, the number of SNPs that
      are sufficient to represent the bias patterns observed from the whole SNP data.
      RESULTS: To estimate the effective SNP size, we developed a novel statistical
      method, SNPKS, which considers both the statistical and biological significances.
      SNPKS consists of two major steps: to obtain an initial effective size by the
      Kolmogorov-Smirnov test (KS test) and to find an intermediate effective size by
      interval evaluation. The SNPKS algorithm was implemented in computer programs and
      applied to the real SNP data. The effective SNP size was estimated to be 38,200,
      39,300, 38,000, and 38,700 in the human, chimpanzee, dog, and mouse genomes,
      respectively, and 39,100, 39,600, 39,200, and 42,200 in human intergenic, genic,
      intronic, and CpG island regions, respectively. CONCLUSION: SNPKS is the first
      statistical method to estimate the effective SNP size. It runs efficiently and
      greatly outperforms the algorithm implemented in SNPNB. The application of SNPKS
      to the real SNP data revealed the similar small effective SNP size (38,000 -
      42,200) in the human, chimpanzee, dog, and mouse genomes as well as in human
      genomic regions. The findings suggest strong influence of genetic factors across
      vertebrate genomes.

PMID- 17196099
TI  - Risk factors for pressure sores in adult patients with myelomeningocele--a
      questionnaire-based study.
AB  - BACKGROUND: Myelomeningocele (MMC) is a part of a complex neural tube defect and
      a disorder of the cerebrospinal fluid system. Pressure sores are a frequent
      complication for patients with MMC. Little is known about the risk factors for
      pressure sores in adults with MMC. The aim of this study was to investigate an
      association between the presence of pressure sores and other patient
      characteristics, in order to develop an improved strategy for the management of
      sores. METHODS: A structured questionnaire regarding sores, medical condition,
      function and living factors was designed and sent to the 193 patients with MMC
      registered in the year 2003 at TRS, a National Centre for Rare Disorders in
      Norway. RESULTS: Out of 193 total, 87 patients participated and 71 patients (82%)
      reported sores; 26 (30%) at the time of the interview and 45 (52%) during the
      last 5 years. Sores were mostly localized on toes and feet and occurred
      exclusively in regions with reduced or missing sensibility. A significant
      association was found between sores and memory deficit (p = 0.02), Arnold Chiari
      malformation (p = 0.02) and a record of previous sores (p = 0.004). Sores were
      not significantly associated with hydrocephalus, syringomyelia, nutrition, body
      mass index, smoking, physical activity, employment or living together with other
      persons. Some patients (18, 21%) reported skin inspection by others and the
      remainder relied on self-inspection. CONCLUSION: Patients with sensory deficit,
      memory problems, and Arnold Chiari malformation had a higher risk of having
      pressure sores. This patient group needs improved skin inspection routines and
      sore treatment.

PMID- 17196098
TI  - Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle
      arrest.
AB  - BACKGROUND: Many chemotherapeutic agents have been used to treat pancreatic
      cancer without success. Apigenin, a naturally occurring flavonoid, has been shown
      to inhibit growth in some cancer cell lines but has not been studied in
      pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer
      cell growth in vitro. RESULTS: Apigenin caused both time- and concentration
      dependent inhibition of DNA synthesis and cell proliferation in four pancreatic
      cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin
      reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25,
      which are all proteins required for G2/M transition. CONCLUSION: Apigenin
      inhibits growth of pancreatic cancer cells through suppression of cyclin B
      associated cdc2 activity and G2/M arrest, and may be a valuable drug for the
      treatment or prevention of pancreatic cancer.

PMID- 17196100
TI  - Improvement in cognitive and psychosocial functioning and self image among
      adolescent inpatient suicide attempters.
AB  - BACKGROUND: Psychiatric treatment of suicidal youths is often difficult and non
      compliance in treatment is a significant problem. This prospective study compared
      characteristics and changes in cognitive functioning, self image and psychosocial
      functioning among 13 to 18 year-old adolescent psychiatric inpatients with
      suicide attempts (n = 16) and with no suicidality (n = 39) METHODS: The two-group
      pre-post test prospective study design included assessments by a psychiatrist, a
      psychologist and medical staff members as well as self-rated measures. DSM-III-R
      diagnoses were assigned using the SCID and thereafter transformed to DSM-IV
      diagnoses. Staff members assessed psychosocial functioning using the Global
      Assessment Scale (GAS). Cognitive performance was assessed using the Wechsler
      Adult Intelligence Scale, while the Offer Self-Image Questionnaire (OSIQ) was
      used to assess the subjects' self-image. ANCOVA with repeated measures was used
      to test changes from entry to discharge among the suicide attempters and non
      suicidal patients. Logistic regression modeling was used to assess variables
      associated with an improvement of 10 points or more in the GAS score. RESULTS:
      Among suicide attempter patients, psychosocial functioning, cognitive performance
      and both the psychological self and body-image improved during treatment and
      their treatment compliance and outcome were as good as that of the non-suicidal
      patients. Suicidal ideation and hopelessness declined, and psychosocial
      functioning improved. Changes in verbal cognitive performance were more
      pronounced among the suicide attempters. Having an improved body-image associated
      with a higher probability of improvement in psychosocial functioning while higher
      GAS score at entry was associated with lower probability of functional
      improvement in both patient groups. CONCLUSION: These findings illustrate that a
      multimodal treatment program seems to improve psychosocial functioning and self
      image among severely disordered suicidal adolescent inpatients. There were no
      changes in familial relationships, possibly indicating a need for more intensive
      family interventions when treating suicidal youths. Multimodal inpatient
      treatment including an individual therapeutic relationship seems recommendable
      for severely impaired psychiatric inpatients tailored to the suicidal
      adolescent's needs.

PMID- 17196101
TI  - Analysis of rice glycosyl hydrolase family 1 and expression of Os4bglu12 beta
      glucosidase.
AB  - BACKGROUND: Glycosyl hydrolase family 1 (GH1) beta-glucosidases have been
      implicated in physiologically important processes in plants, such as response to
      biotic and abiotic stresses, defense against herbivores, activation of
      phytohormones, lignification, and cell wall remodeling. Plant GH1 beta
      glucosidases are encoded by a multigene family, so we predicted the structures of
      the genes and the properties of their protein products, and characterized their
      phylogenetic relationship to other plant GH1 members, their expression and the
      activity of one of them, to begin to decipher their roles in rice. RESULTS: Forty
      GH1 genes could be identified in rice databases, including 2 possible endophyte
      genes, 2 likely pseudogenes, 2 gene fragments, and 34 apparently competent rice
      glycosidase genes. Phylogenetic analysis revealed that GH1 members with closely
      related sequences have similar gene structures and are often clustered together
      on the same chromosome. Most of the genes appear to have been derived from
      duplications that occurred after the divergence of rice and Arabidopsis thaliana
      lineages from their common ancestor, and the two plants share only 8 common gene
      lineages. At least 31 GH1 genes are expressed in a range of organs and stages of
      rice, based on the cDNA and EST sequences in public databases. The cDNA of the
      Os4bglu12 gene, which encodes a protein identical at 40 of 44 amino acid residues
      with the N-terminal sequence of a cell wall-bound enzyme previously purified from
      germinating rice, was isolated by RT-PCR from rice seedlings. A thioredoxin
      Os4bglu12 fusion protein expressed in Escherichia coli efficiently hydrolyzed
      beta-(1,4)-linked oligosaccharides of 3-6 glucose residues and laminaribiose.
      CONCLUSION: Careful analysis of the database sequences produced more reliable
      rice GH1 gene structure and protein product predictions. Since most of these
      genes diverged after the divergence of the ancestors of rice and Arabidopsis
      thaliana, only a few of their functions could be implied from those of GH1
      enzymes from Arabidopsis and other dicots. This implies that analysis of GH1
      enzymes in monocots is necessary to understand their function in the major grain
      crops. To begin this analysis, Os4bglu12 beta-glucosidase was characterized and
      found to have high exoglucanase activity, consistent with a role in cell wall
      metabolism.

PMID- 17196102
TI  - The Virtual Insect Brain protocol: creating and comparing standardized
      neuroanatomy.
AB  - BACKGROUND: In the fly Drosophila melanogaster, new genetic, physiological,
      molecular and behavioral techniques for the functional analysis of the brain are
      rapidly accumulating. These diverse investigations on the function of the insect
      brain use gene expression patterns that can be visualized and provide the means
      for manipulating groups of neurons as a common ground. To take advantage of these
      patterns one needs to know their typical anatomy. RESULTS: This paper describes
      the Virtual Insect Brain (VIB) protocol, a script suite for the quantitative
      assessment, comparison, and presentation of neuroanatomical data. It is based on
      the 3D-reconstruction and visualization software Amira, version 3.x (Mercury
      Inc.) 1. Besides its backbone, a standardization procedure which aligns
      individual 3D images (series of virtual sections obtained by confocal microscopy)
      to a common coordinate system and computes average intensities for each voxel
      (volume pixel) the VIB protocol provides an elaborate data management system for
      data administration. The VIB protocol facilitates direct comparison of gene
      expression patterns and describes their interindividual variability. It provides
      volumetry of brain regions and helps to characterize the phenotypes of brain
      structure mutants. Using the VIB protocol does not require any programming skills
      since all operations are carried out at an intuitively usable graphical user
      interface. Although the VIB protocol has been developed for the standardization
      of Drosophila neuroanatomy, the program structure can be used for the
      standardization of other 3D structures as well. CONCLUSION: Standardizing brains
      and gene expression patterns is a new approach to biological shape and its
      variability. The VIB protocol provides a first set of tools supporting this
      endeavor in Drosophila. The script suite is freely available at
      http://www.neurofly.de2.

PMID- 17196103
TI  - Array-CGH and multipoint FISH to decode complex chromosomal rearrangements.
AB  - BACKGROUND: Recently, several high-resolution methods of chromosome analysis have
      been developed. It is important to compare these methods and to select reliable
      combinations of techniques to analyze complex chromosomal rearrangements in
      tumours. In this study we have compared array-CGH (comparative genomic
      hybridization) and multipoint FISH (mpFISH) for their ability to characterize
      complex rearrangements on human chromosome 3 (chr3) in tumour cell lines. We have
      used 179 BAC/PAC clones covering chr3 with an approximately 1 Mb resolution to
      analyze nine carcinoma lines. Chr3 was chosen for analysis, because of its
      frequent rearrangements in human solid tumours. RESULTS: The ploidy of the tumour
      cell lines ranged from near-diploid to near-pentaploid. Chr3 locus copy number
      was assessed by interphase and metaphase mpFISH. Totally 53 chr3 fragments were
      identified having copy numbers from 0 to 14. MpFISH results from the BAC/PAC
      clones and array-CGH gave mainly corresponding results. Each copy number change
      on the array profile could be related to a specific chromosome aberration
      detected by metaphase mpFISH. The analysis of the correlation between real copy
      number from mpFISH and the average normalized inter-locus fluorescence ratio
      (ANILFR) value detected by array-CGH demonstrated that copy number is a linear
      function of parameters that include the variable, ANILFR, and two constants,
      ploidy and background normalized fluorescence ratio. CONCLUSION: In most cases,
      the changes in copy number seen on array-CGH profiles reflected cumulative
      chromosome rearrangements. Most of them stemmed from unbalanced translocations.
      Although our chr3 BAC/PAC array could identify single copy number changes even in
      pentaploid cells, mpFISH provided a more accurate analysis in the dissection of
      complex karyotypes at high ploidy levels.

PMID- 17196104
TI  - Uptake of 3H-cAMP by retinal pigment epithelium isolated from bluegill sunfish
      (Lepomis macrochirus).
AB  - BACKGROUND: In bluegill sunfish, the melanin-containing pigment granules of the
      retinal pigment epithelium undergo cyclic movements in response both to ambient
      lighting and circadian cues. Pigment granules aggregate into the cell body at
      night (in the dark), and disperse into apical processes during the day (in the
      light). Regulation of pigment granule aggregation in a number of fishes depends
      on modulating the intracellular levels of cyclic adenosine monophosphate.
      RESULTS: Here we show isolated RPE takes up cyclic adenosine monophosphate (cAMP)
      in a saturable manner, exogenously applied cAMP induces pigment granule
      aggregation in retinal pigment epithelium isolated from bluegill, and aggregation
      induced in this manner is inhibited by treatment with probenecid, an organic
      anion transport inhibitor. CONCLUSION: Our results raise the possibility that
      cAMP functions as a messenger secreted from the neural retina to signal darkness
      to the RPE, which takes it up. It further suggests that organic anion transport
      systems are the route by which cAMP crosses RPE cell membranes since probenecid
      inhibits extracellular cAMP from causing pigment granule aggregation.

PMID- 17196105
TI  - The cost of uncomplicated childhood fevers to Kenyan households: implications for
      reaching international access targets.
AB  - BACKGROUND: Fever is the clinical hallmark of malaria disease. The Roll Back
      Malaria (RBM) movement promotes prompt, effective treatment of childhood fevers
      as a key component to achieving its optimistic mortality reduction goals by 2010.
      A neglected concern is how communities will access these new medicines promptly
      and the costs to poor households when they are located in rural areas distant to
      health services. METHODS: We assemble data developed between 2001 and 2002 in
      Kenya to describe treatment choices made by rural households to treat a child's
      fever and the related costs to households. Using a cost-of-illness approach, we
      estimate the expected cost of a childhood fever to Kenyan households in 2002. We
      develop two scenarios to explore how expected costs to households would change if
      more children were treated at a health care facility with an effective
      antimalarial within 48 hours of fever onset. RESULTS: 30% of uncomplicated fevers
      were managed at home with modern medicines, 38% were taken to a health care
      facility (HCF), and 32% were managed at home without the use of modern medicines.
      Direct household cash expenditures were estimated at $0.44 per fever, while the
      total expected cost to households (cash and time) of an uncomplicated childhood
      fever is estimated to be $1.91. An estimated mean of 1.42 days of caretaker time
      devoted to each fever accounts for the majority of household costs of managing
      fevers. The aggregate cost to Kenyan households of managing uncomplicated
      childhood fevers was at least $96 million in 2002, equivalent to 1.00% of the
      Kenyan GDP. Fewer than 8% of all fevers were treated with an antimalarial drug
      within 24 hours of fever onset, while 17.5% were treated within 48 hours at a
      HCF. To achieve an increase from 17.5% to 33% of fevers treated with an
      antimalarial drug within 48 hours at a HCF (Scenario 1), children already being
      taken to a HCF would need to be taken earlier. Under this scenario, direct cash
      expenditures would not change, and total household costs would fall slightly to
      $1.86 because caretakers also save time with prompt treatment if the child has
      malaria. CONCLUSION: The management of uncomplicated childhood fevers imposes
      substantial costs on Kenyan households. Achieving substantial improvements in the
      numbers of fevers treated within 48 hours at a HCF with an effective antimalarial
      drug (Scenario 1) will not impose additional costs on households. Achieving
      additional improvements in fevers treated promptly at a HCF (Scenario 2) will
      impose additional costs on some households roughly equal to average cash expenses
      for transportation to a HCF. Additional financing mechanisms that further reduce
      the costs of accessing care at a HCF and/or that make artemisinin-based
      combination therapies (ACTs) accessible for home management need to be developed
      and evaluated as a top priority.

PMID- 17196106
TI  - Improved outcomes in patients with chronic obstructive pulmonary disease treated
      with salmeterol compared with placebo/usual therapy: results of a meta-analysis.
AB  - BACKGROUND: Several studies have demonstrated that long-acting beta2-agonists
      such as salmeterol are beneficial in chronic obstructive pulmonary disease
      (COPD). A meta-analysis was therefore conducted to review studies in COPD to
      provide pooled estimates of the effect of salmeterol 50 mcg taken twice daily in
      addition to usual therapy on several clinically relevant endpoints, when compared
      with placebo/usual therapy. METHODS: An extensive search of literature and
      clinical trial databases was conducted using the terms salmeterol, COPD, chronic,
      obstructive, bronchitis and emphysema. Nine randomized, double-blind, parallel
      group, placebo-controlled trials of > or =12 week duration with salmeterol 50 mcg
      bid treatment in COPD were included (>3500 patients), with a further 14 trials
      excluded due to study design or reporting timelines. All patients were included,
      and a sub-group of subjects (84%) with poorly reversible COPD were considered
      separately. Statistical testing was carried out at the 5% level, except for
      interaction testing which was carried out at the 10% level. RESULTS: Patients
      treated with salmeterol over 12 months were less likely to withdraw early from
      the studies (19% patients compared with 25% on their current usual therapy, p <
      0.001), less likely to suffer a moderate/severe exacerbation (34% compared with
      39%, p < 0.0001) and had a greater increase in average FEV1 (73 mL difference vs
      placebo/usual therapy, p < 0.0001). Similar differences were found at 3 and 6
      months. At all time points, more patients experienced an improvement in health
      status and also a greater change with salmeterol than with placebo/usual therapy
      (p < 0.002). There was no evidence of tachyphylaxis to salmeterol over 12 months.
      CONCLUSION: The meta-analysis confirmed clinically and statistically significant,
      sustained and consistent superiority of salmeterol 50 mcg bid over placebo/usual
      therapy on a broad range of outcome measures.

PMID- 17196108
TI  - Hindcasting of nutrient loadings from its catchment on a highly valuable coastal
      lagoon: the example of the Fleet, Dorset, UK, 1866-2004.
AB  - BACKGROUND: Nutrient loadings from its catchment upon The Fleet, a highly
      valuable coastal lagoon in Southern England, were hindcast for the period AD 1866
      2004, using a catchment model, export coefficients, and historical data on land
      use changes, livestock numbers, and human population. Agriculture was the main
      nutrient source throughout, other inputs representing minor contributions.
      Permanent pasture was historically the main land use, with temporary grassland
      and cereals increasing during the mid-20th century. Sheep, the main 19th century
      livestock, were replaced by cattle during the 1930s. RESULTS: Total nitrogen
      loadings rose from ca 41 t yr-1 during the late 19th century to 49-54 t yr-1 for
      the mid-20th, increasing to 98 t yr-1 by 1986. Current values are ca 77 t yr-1.
      Total phosphorus loads increased from ca 0.75 t yr-1 for the late 19th century to
      ca 1.6 t yr-1 for the mid-20th, reached ca 2.2 t yr-1 in 1986, and are now ca 1.5
      t yr-1. Loadings rose most rapidly between 1946 and 1988, owing to increased use
      of inorganic fertilisers, and rising sheep and cattle numbers. Livestock were the
      main nutrient source throughout, but inputs from inorganic fertilisers increased
      after 1946, peaking in 1986. Sewage treatment works and other sources contribute
      little nitrogen, but ca 35% of total phosphorus. Abbotsbury Swannery, an ancient
      Mute Swan community, provides ca 0.5% of total nitrogen, and ca 5% of total
      phosphorus inputs. CONCLUSION: The Fleet has been grossly overloaded with
      nitrogen since 1866, climaxing during the 1980s. Total phosphorus inputs lay
      below 'permissible' limits until the 1980s, exceeding them in inner, less tidal
      parts of the lagoon, during the 1940s. Loadings on Abbotsbury Bay exceeded
      'permissible' limits by the 1860s, becoming 'dangerous' during the mid-20th
      century. Phosphorus stripping at point sources will not significantly reduce
      loadings to all parts of the lagoon. Installation of 5 m buffer strips throughout
      the catchment and shoreline will marginally affect nitrogen loadings, but will
      reduce phosphorus inputs to the West Fleet below 'permissible' limits. Only a
      combination of measures will significantly affect Abbotsbury Bay, where, without
      effluent diversion, loadings will remain beyond 'permissible'.

PMID- 17196107
TI  - p66 Shc and tyrosine-phosphorylated Shc in primary breast tumors identify
      patients likely to relapse despite tamoxifen therapy.
AB  - INTRODUCTION: Shc adapter proteins are secondary messenger proteins involved in
      various cellular pathways, including those mediating receptor tyrosine kinase
      signaling and apoptosis in response to stress. We have previously reported that
      high levels of tyrosine-phosphorylated Shc (PY-Shc) and low levels of its
      inhibitory p66 Shc isoform are strongly prognostic for identifying both early
      node-negative and more advanced, node-positive, primary breast cancers with high
      risk for recurrence. Because aberrant activation of tyrosine kinases upstream of
      Shc signaling proteins has been implicated in resistance to tamoxifen--the most
      widely prescribed drug for treatment of estrogen receptor-positive breast cancer-
      we hypothesized that Shc isoforms may identify patients at increased risk of
      relapsing despite tamoxifen treatment. METHODS: Immunohistochemical analyses of
      PY-Shc and p66 Shc were performed on archival primary breast cancer tumors from a
      population-based cohort (60 patients, 9 relapses) and, for validation, an
      independent external cohort (31 patients, 13 relapses) in which all patients
      received tamoxifen as a sole systemic adjuvant prior to relapse. RESULTS: By
      univariate and multivariate analyses, the Shc proteins were very strong and
      independent predictors of treatment failure in both the population-based cohort
      (interquartile hazard ratio = 8.3, 95% confidence interval [CI] 1.8 to 38, P =
      0.007) and the validating cohort (interquartile relative risk = 12.1, 95% CI 1.7
      to 86, P = 0.013). CONCLUSION: These results suggest that the levels of PY-Shc
      and p66 Shc proteins in primary tumors identify patients at high risk for
      relapsing despite treatment with tamoxifen and therefore with further validation
      may be useful in guiding clinicians to select alternative adjuvant treatment
      strategies.

PMID- 17196110
TI  - Using cost-effectiveness analyses to inform policy: the case of antiretroviral
      therapy in Thailand.
AB  - BACKGROUND: Much emphasis is put on providing evidence to assist policymakers in
      priority setting and investment decisions. Assessing the cost-effectiveness of
      interventions is one technique used by policymakers in their decisions around the
      allocation of scarce resources. However, even where such evidence is available,
      other considerations may also be taken into account, and even over-ride technical
      evidence. Antiretroviral therapy (ART) is the most effective intervention to
      reduce HIV-related morbidity and prolong mortality. However, treatment provision
      in the developing world has been hindered by the high costs of services and
      drugs, casting doubts on its cost-effectiveness. This paper looks at Thailand's
      publicly-funded antiretroviral initiative which was first introduced in 1992, and
      explores the extent to which cost-effectiveness evidence influenced policy.
      METHODS: This article reviews the development of the national ART programme in
      Thailand between 1992 and 2004. It examines the roles of cost-effectiveness
      information in treatment policy decisions. Qualitative approaches including
      document analysis and interview of key informants were employed. RESULTS: Two
      significant policy shifts have been observed in government-organised ART
      provision. In 1996, service-based therapy for a few was replaced by a research
      network to support clinical assessments of antiretroviral medication in public
      hospitals. This decision was taken after a domestic study illustrated the
      unaffordable fiscal burden and inefficient use of resources in provision of ART.
      The numbers of treatment recipients was maintained at 2,000 per year throughout
      the 1990s. It was not until 2001 that a new government pledged to extend the
      numbers receiving the service, as part of its commitment to universal coverage.
      Several elements played a role in this decision: new groups of dominant actors,
      drug price reductions, a pro-active civil society movement, lessons from
      experience on treatment benefits, and global treatment advocacy. Unlike previous
      policy discourse, human rights, ethics and equity notions were explicitly raised
      to support therapy extension. CONCLUSION: In the early decision, moving from a
      relatively limited ART service to a research network was clearly influenced by
      cost-effectiveness data. But in the 2001 decision to include ART in the universal
      coverage package, cost-effectiveness arguments were over-ruled by other
      considerations. Thai ART policy was shaped by many factors, and was not a simple
      rational process which relied on evidence.

PMID- 17196109
TI  - Role of histamine as a putative inhibitory transmitter in the honeybee antennal
      lobe.
AB  - BACKGROUND: Odors are represented by specific spatio-temporal activity patterns
      in the olfactory bulb of vertebrates and its insect analogue, the antennal lobe.
      In honeybees inhibitory circuits in the AL are involved in the processing of
      odors to shape afferent odor responses. GABA is known as an inhibitory
      transmitter in the antennal lobe, but not all interneurons are GABAergic.
      Therefore we sought to analyze the functional role of the inhibitory transmitter
      histamine for the processing of odors in the honeybee AL. RESULTS: We optically
      recorded the representation of odors before, during and after histamine
      application at the input level (estimated from a compound signal), and at the
      output level (by selectively measuring the projection neurons). For both,
      histamine led to a strong and reversible reduction of odor-evoked responses.
      CONCLUSION: We propose that histamine, in addition to GABA, acts as an inhibitory
      transmitter in the honeybee AL and is therefore likely to play a role in odor
      processing.

PMID- 17196111
TI  - Recent advances in basic neurosciences and brain disease: from synapses to
      behavior.
AB  - Understanding basic neuronal mechanisms hold the hope for future treatment of
      brain disease. The 1st international conference on synapse, memory, drug
      addiction and pain was held in beautiful downtown Toronto, Canada on August 21
      23, 2006. Unlike other traditional conferences, this new meeting focused on three
      major aims: (1) to promote new and cutting edge research in neuroscience; (2) to
      encourage international information exchange and scientific collaborations; and
      (3) to provide a platform for active scientists to discuss new findings. Up to 64
      investigators presented their recent discoveries, from basic synaptic mechanisms
      to genes related to human brain disease. This meeting was in part sponsored by
      Molecular Pain, together with University of Toronto (Faculty of Medicine,
      Department of Physiology as well as Center for the Study of Pain). Our goal for
      this meeting is to promote future active scientific collaborations and improve
      human health through fundamental basic neuroscience researches. The second
      international meeting on Neurons and Brain Disease will be held in Toronto
      (August 29-31, 2007).

PMID- 17196112
TI  - Liver metastases of pancreatic acinar cell carcinoma with marked nuclear atypia
      and pleomorphism diagnosed by EUS FNA cytology: a case report with emphasis on
      FNA cytological findings.
AB  - BACKGROUND: Acinar cell carcinoma of the pancreas is a rare neoplasm. Although
      this tumor has been well characterized histologically, the morphological patterns
      in Fine Needle Aspiration Cytology have not been well defined. Unlike ductal
      adenocarcinomas, endocrine tumors, and solid pseudopapillary tumors of the
      pancreas with their characteristic FNA cytological features, acinar cell
      carcinomas pose a particular diagnostic challenge by sharing many cytomorphologic
      features with endocrine tumors of the pancreas. CASE PRESENTATION: A 37-year-old
      man presented with lower chest and left upper quadrant abdominal pain. Computed
      tomography revealed a 7.8 x 7.3 cm irregular, partially cystic mass in the body
      and tail of the pancreas, and two lesions in the liver compatible with
      metastases. Subsequently, the patient underwent endoscopic ultrasound-guided fine
      needle aspiration on one of the two metastatic liver masses. FNA cytology
      revealed abundant, loosely cohesive clusters of malignant epithelial cells with
      vaguely acinar and trabecular formations. The pleomorphic nuclei had fine
      granular chromatin and occasionally small nucleoli. There were scant to moderate
      amounts of cytoplasm. Scattered, strikingly large tumor cells with giant nuclei,
      prominent mitoses and associated necrosis were evident. A pancreatic endocrine
      tumor was suspected initially, but acinar cell carcinoma of the pancreas was
      confirmed by immunohistochemistry, cytochemical and ultrastructural studies.
      CONCLUSION: We describe a case of pancreatic acinar cell carcinoma with unusual
      cytomorphologic features mimicking an endocrine tumor of pancreas, encountered in
      endoscopic ultrasound-guided fine needle aspiration of a metastatic liver mass
      and discuss the diagnostic approach for this unusual pancreatic tumor in fine
      needle aspiration cytology.

PMID- 17196113
TI  - Qualitative analysis of the impact of a lymphatic filariasis elimination
      programme using mass drug administration on Misima Island, Papua New Guinea.
AB  - BACKGROUND: Papua New Guinea is the only endemic country in the Western Pacific
      Region that has not yet introduced a countrywide programme to eliminate lymphatic
      filariasis. However, on Misima Island in Milne Bay Province, government and
      private sectors have collaborated to implement a pilot elimination programme.
      Although interim evaluation indicated that the programme has been
      parasitologically successful, an appreciation that sustainable health gains
      depend on understanding and accommodating local beliefs prompted this qualitative
      study. METHODS: We investigated Misima community members knowledge and attitudes
      about lymphatic filariasis and the elimination programme. A combination of focus
      groups and key informant interviews were used to explore participants perceptions
      of health; knowledge of the aetiology and symptoms of filariasis, elephantiasis
      and hydrocele; attitudes towards the disease and mass drug distribution; and the
      social structure and decision-making protocols within the villages. RESULTS:
      Focus group discussions proved inferior to key informant interviews for gathering
      rich data. Study participants did not consider lymphatic filariasis ("pom") a
      major health problem but were generally positive about mass drug administration
      campaigns. A variety of conditions were frequently and incorrectly attributed to
      filariasis. Participants expressed the belief that individuals infected with
      filariasis always had visible manifestations of disease. A common misconception
      was that taking drugs during campaigns provided long-term immunity against
      disease. The role of mosquito vectors in transmission was not generally
      appreciated and certain clinical presentations, particularly hydrocele, were
      associated with supernatural forces. Multiple adverse events were associated with
      mass drug administration campaigns and most study participants mentioned
      community members who did not participate in campaigns. CONCLUSION: Important
      issues requiring educational intervention and elimination activity modification
      in the Misima region were identified during this study. Research outcomes should
      assist Papua New Guinea in developing and implementing a national elimination
      strategy and inform discussions regarding the appropriateness of current
      elimination strategies.

PMID- 17196114
TI  - Natural infection by Paramphistomoidea Stiles and Goldberger, 1910 trematodes in
      wild Marsh Deer (Blastocerus dichotomus Illiger, 1815) from Sergio Mottas's
      hydroelectric power station flooding area.
AB  - Studies on helminthfauna of marsh deer Blastocerus dichotomus Illiger, 1815 are
      rare, although helminthic diseases are an important cause of mortality in these
      animals. Fifteen male and female adult marsh deer from Sergio Motta's
      hydroelectric power station flooding area at Parana River which died during the
      capture and quarantine procedures, between 1998 and 1999, were necropsied. Three
      trematodes species, Paramphistomum cervi, Balanorchis anastrofus and Zygocotyle
      lunatum, all belonging to superfamily Paramphistomoidea, were identified. The
      obtained trematodes were identified, counted and their respectives descriptors of
      infection were determined. All necropsied animals were infected by helminths.
      Paramphistomum cervi was the most prevalent species, while Zygocotyle lunatum was
      found in only one animal.

PMID- 17196115
TI  - [The effect of different strains Babesia bovis (Babes, 1888) on tick of Boophilus
      microplus (Canestrini, 1887)].
AB  - Two samples (modified and no-modified) of Babesia bovis, were used to evaluate
      the effect on engorged females of Boophilus microplus Babesia spp - free. For so
      much, were used three holstein breed bovine, males with 6 months of age, (BH1,
      BH2 and BH3), coming of the Plateau of Itatiaia, Rio de Janeiro, Brazil. Each
      calf was infested with 0.2g of B. microplus larvae Babesia spp- free, for 10
      consecutive days. They were inoculated in the calves BH1 and BH2, modified and no
      modified sample, respectively. After natural fall of adults ticks from the
      vertebrate host, 100 engorged females of each host (BH1, BH2 and BH3) were
      incubated in BOD, with superior Relative Humidity up 80%, Temperature of 28
      degrees C, were appraised daily until the 12th day post incubation (dpi.). In the
      group of the engorged females obtained of calf BH1, infection of ticks was not
      observed, to the haemolymph exam and oviposture. The sporokinets absence in these
      samples was related with the successive passages in splenectomized calves and the
      criopreservation of the sample. In engorged females from BH2 it was observed
      rates of infection of 100% and 82% of mortality in 7th dpi. and 100% until 12nd
      dpi., as the oviposture, 70% did not make oviposition and 30% made it until 7th
      dpi.

PMID- 17196116
TI  - [Miticidal efficacy of thiabendazole against Otodectes cynotis (Hering, 1838) in
      dogs].
AB  - The aim of the present study was to evaluate the efficacy of thiabendazole on the
      treatment of Otodectes cynotis infestations in dogs. Ten naturally infested
      beagle dogs were used. The mites were diagnosed through otoscopy. Dogs were
      examined three days before treatment (day -3) and on the treatment day (day 0).
      They were randomly divided into two groups, five animals for the control group
      and five for the treated. During seven days, was applied in both ears of the
      treated dogs 1ml of the thiabendazole 5% solution, which correspond to 50mg of
      the product. All animals were reexamined through otoscopy on days +1, +3, +7,
      +10, +17, +24 and +31. The dogs on the control group showed mites in both ears
      during the whole period of observation. On the treated group the efficacy varied
      from 20% on the left ear to 80% on the right ear, on the first day after
      treatment. On days +3, +7, +10, +17, +24 and +31 the medium efficacy was 100% on
      both ears. The thiabendazole was efficient on the elimination of O. cynotis in
      dogs when used on the dose of 50mg per ear during seven following days.

PMID- 17196117
TI  - [Prevalence and control of gastrintestinal parasitosis in calves from dairy farms
      in the municipality of Alegre, Espirito Santo].
AB  - The objectives of the present study were to evaluate the prevalence of
      gastrintestinal helminthosis of calves and to identify control aspects related to
      these infections in dairy farms of the municipality of Alegre, Espirito Santo. A
      total of 222 calves varying of one to 18 months of age were examined and
      proportionally divided between 12 dairy farms. After techniques in the laboratory
      of parasitic diseases of the veterinary hospital of Centro de Ciencias Agrarias
      of the Universidade Federal do Espirito Santo, the prevalence of eggs of
      Strongyloidea, Trichuris sp., Moniezia sp, Strongyloides papillosus and coccidial
      oocysts were, in properties and calves: 100 and 66; 100 and 57.8; 50 and 8.2; 25
      and 1.8, and 33.3 and 7.8%, respectivelly. Of the 66 for eggs of the
      Strongyloidea, 64 were attributed to Haemonchus spp. and 53.75% to Cooperia spp.
      Despite the existence of parasite control programs in the farms, were identify
      some wrong practices, as lack of weighting animals for the calculation of the
      dose rate of the drugs and lack of use of the compost of excrements. Thus, the
      drugs uses of incorrect form may be able to cause future damages with development
      of parasites resistance to these products.

PMID- 17196118
TI  - [Evaluation of cellular response in engorged females of Boophilus microplus
      (Canestrini, 1887) inoculated with Metarhizium anisopliae, Beauveria bassiana,
      Penicillium corylophilum or Fusarium oxysporum].
AB  - The effect of Beauveria bassiana, Metarhizium anisopliae, Penicillium
      corylophilum or Fusarium oxysporum on the dynamic of hemocytes presented in the
      haemolymph of engorged females of Boophilus microplus was studied. The
      inoculation was carried out with conidia suspension of different fungi in the
      concentration of 10(8) conidia/ml. A negative control group was inoculated with
      0.1% Tween 80 water solution and a testimony group was comprised of non
      inoculated ticks. The haemolymph samples were collected in 24, 48 and 72 hours
      post-challenge. In all the studied periods, prohemocytes, plasmatocytes,
      granulocytes, spherulocytes and oenocytoids were observed in the specimens
      inoculated with fungus and also in the controls groups (negative and testimony).
      Prohemocytes, plasmatocytes and spherulocytes were the most cells in the
      haemolymph. The absence of hemocytes 72h post-challenging was observed prior to
      the death of the specimens inoculated with B. bassiana suggesting a failure in
      the cellular response. Hyphae and conidia growth was observed in the samples
      treated with entomopathogenic fungi (B. bassiana or M. anisopliae). The groups
      treated with non entomopathogenic fungi (P. corylophilum or F. oxysporum) did not
      shown significant differences in relation to the negative control and testimony
      groups.

PMID- 17196119
TI  - [In vitro patogenicity of the fungi Metarhizium anisopliae (Metschnikoff, 1879)
      Sorokin, 1883, on the tick Boophilus microplus (Canestrini,1887)].
AB  - The cattle tick Boophilus microplus is a serious concern to the Brazilian cattle
      industry. It causes decreased meat and milk production, low alimentary
      conversion, damage to leather and transmission of pathogens. The use of
      entomopathogenic fungi as biological control agents for ticks has shown promising
      results. This study tests the in vitro effects of two Metarhizium anisopliae
      isolates (E9 and 319) towards three stages of B. microplus: eggs, larvae and
      engorged females. The bioassays were composed of five treatment groups
      (concentrations: 10(5), 10(6), 10(7), 10(8) conidia/ml and the control) each one
      with ten repetitions. The stages were treated by immersion for three minutes.
      After the treatments, the females, eggs and larvae were incubated at 27 degrees C
      +/- 1 and RH >or= 80%. The main studied parameters were: percentage of larvae
      eclosion, percentage of larvae mortality and the indexes of nutritional and
      reproductive efficiency. In vitro tests of the fungal isolates showed effective
      control of the three stages of B. microplus, suggesting high potential for their
      use as a microbial control agent of the B. microplus tick.

PMID- 17196120
TI  - [Species from genus Eimeria observed in domestic rabbit (Oryctolagus cuniculus)
      feces raised at the Municipality of Campos dos Goytacazes in the State of Rio de
      Janeiro, Brazil].
AB  - This study was designed to identify species of the genus Eimeria from eleven
      rabbit meat breeders from Campos dos Goytacazes. Fecal samples were collected
      from rabbits with different health conditions and consintence of feces. The
      following species of Eimeria were identified: E. perforans; E. magna; E.
      coecicola; E. irresidua; E. media; E. flavescens; E. nagpurensis; E.
      intestinalis, E. exigua and E. stiedae. Parasites from this genus were detected
      in 81.82% (9) of the rabbit meat production sites, regardless of the management
      and hygiene conditions. In all cases the infection was always caused from more
      than one species of Eimeria.

PMID- 17196121
TI  - [Community ecology of the metazoan parasites of five Scombrid species
      (Perciformes: Scombridae), from the coastal zone of the State of Rio de Janeiro,
      Brazil].
AB  - From June 2001 to March 2004, 171 marine scombrid fishes (Perciformes:
      Scombridae) from the coastal zone of the State of Rio de Janeiro, Brazil (21-23
      degrees S, 41-45 degrees W) were necropsied to study their community metazoan
      parasites: 46 Euthynnus alleteratus (Rafinesque, 1810); 15 Katsuwonus pelamis
      (Linnaeus, 1758); 30 Sarda sarda (Bloch, 1793) ; 43 Scomber scombrus Linnaeus,
      1758 and 37 Scomberomorus brasiliensis Collette, Russo & Zavala-Camim, 1978. All
      specimens of E. alleteratus, K. pelamis and S. brasiliensis were parasitized by
      one or more metazoan species. In S. sarda and S. scombrus 96.7% and 60.4% of
      specimens were parasitized, respectively. Forty-four different metazoan parasites
      species were collected: 22 in E. alleteratus, 13 in K. pelamis, 14 in S. sarda,
      three in S. scombrus and 12 in S. brasiliensis. Euthynnus alleteratus is a new
      host record for 12 metazoan parasite species, K. pelamis and S. scombrus for one
      species each, S. sarda for eighth species and S. brasiliensis for five species.
      Nine parasites species were new geographical record. Fifteen species were common
      in at least two communities. The digeneans were the majority of the parasite
      specimens collected in E. alleteratus and S. brasiliensis with 85.7% and 72.5%,
      respectively. In K. pelamis and S. sarda the majority of the parasite specimens
      collected were cestodes and copepods, 64.5% and 62.9%, respectively. Only larval
      stages of nematodes were collected in S. scombrus. The parasite of 5 host species
      showed the typical aggregate pattern of distribution. Four cases of positive
      correlation and three cases of negative correlation between host's length and
      prevalence and parasite abundance were found. The parasite community of K.
      pelamis showed the higher values of the mean parasite species richness and
      diversity. Only in S. scombrus the abundance and parasite species richness were
      correlates with the host's length. Euthynnus alleteratus was the species with the
      higher number of ectoparasites (11), adult endoparasites (5) and larval stage of
      endoparasites (6). The infracommunities of larval stage of endoparasites showed
      correlation with the host's length and abundance, parasite species richness,
      diversity and numerical dominance.

PMID- 17196122
TI  - [Viability of nematophagous fungi Arthrobotrys robusta, Duddingtonia flagrans and
      Monacrosporium thaumasium after sporulation in different culture media].
AB  - Due to the shortage of studies that indicate the culture mediums that optimize
      the sporulation of namatophagous fungi for use in researche, the sporulation of
      the fungal isolates A. robusta (I31), D. flagrans (CG768) and M. thaumasium
      (NF34A) was evaluated in laboratorial conditions for 10 days in the means water
      agar 2% (WA 2%), potato-dextrose-agar 2% (PDA 2%), corn-meal-agar 2% (CMA 2%) and
      yeast-phosphate-sulphate-sucrose-agar (YPSSA). The largest conidia production (P
      < 0.05) for the isolate CG768 happened in BDA 2% while in the isolates I31 and
      NF34A produced larger conidia number in YPSSA (P < 0.05). The viability of the
      conidia to prey infective Ancylostoma spp. larvae did not lose its effectiveness
      (P < 0.05) independent of the culture medium. The middle of culture did not
      influence in the viability of the conidia (P > 0.05).

PMID- 17196123
TI  - Distribution of antibodies against Neospora caninum, BVDV and BHV-1 among cows in
      brazilian dairy herds with reproductive disorders.
AB  - Neospora caninum, bovine viral diarrhea virus (BVDV) and bovine herpes virus 1
      (BHV-1) are worldwide spread pathogens associated with reproductive problems in
      cattle. The present work aimed to observe the infection pattern of these three
      pathogens in two dairy herds with distinct reproductive managements from
      Triangulo Mineiro, Minas Gerais State, Brazil. The herds were not vaccinated
      against either N. caninum, BVDV or BHV-1. Blood samples were collected and
      analyzed for presence of specific antibodies, and N. caninum IgG avidity was
      measured in N. caninum positive samples. In herd 1, 34 out of 174 sampled cows
      (20%) had antibodies to N. caninum and the seropositivity of BVDV and BHV-1 were
      62% and 86%, respectively. Of 69 sampled cows in herd 2. 7 (10%) had antibodies
      to N. caninum, and 49% and 39% were seropositive to BVDV and BHV-1, respectively.
      The IgG avidity profiles indicated that N. caninum had been present in both herds
      for some years and that herd 1 had an ongoing horizontal spread of the parasite.
      The results indicate that the studied reproductive pathogens were present in the
      herds and partly may have contributed to their reproductive problems.

PMID- 17196124
TI  - [The effect of betain on biology and morphology of developmental stages of
      Eimeria acervulina in broiler chicks experimentally infected].
AB  - Purposing to investigate the betaine effect on biology and morphology of
      developmental stages of Eimeria acervulina, 420 broiler chicks Cobb were
      experimentally inoculated with 2 x 10(5) sporulated oocysts and housed in battery
      cages in a block design with five treatments and six replicates each, including a
      positive control, a group treated with salinomycin and growth promoter plus three
      levels of betaine as additive in the feed at 0.05, 0.10 and 0.15%. Measurements
      of oocysts, sporocysts and endogenous stages were performed as morphological
      parameters, while pre patent and patent periods and sporulation time were taken
      as biological parameters. Morphology was also associated with the mathematical
      constant Phi (1.618) to evaluate possible relationship. Betaine was able to cause
      modifications in both biology and morphology of oocysts and sporocysts, whereas
      it was weakly able to affect developmental stages based on trophozoites and
      macrogamonts measurements. According to the measures of sporocysts E. acervulina
      development was closely related to Phi.

PMID- 17196125
TI  - [Larvae culture of ovine gastrintestinal nematodes in sawdust substrates of Pinus
      taeda, P. elliottii and Araucaria angustifolia].
AB  - The aim of this study was to verify the influence of sawdust substrates obtained
      from wood treated with sodium tribromophenate and not treated of Pinus elliotti,
      P. taeda, and Araucaria angustifolia in larval cultures of ovine gastrintestinal
      helminths. Feces samples were collected between 8 to 12am, from a lamb naturally
      infected with gastrintestinal nematodes and analysed by the modified Mc Master
      technique for worm egg counting (epg). Six groups of 20g of feces were prepared.
      Each group received 5g of one of the sawdust substrates and 5ml of distilled
      water. The material has been processed, identified and taken to a climatized
      chamber with a temperature of 27 +/- 1 degrees C, relative humidity above 70%,
      and in escotophase for seven days. The third stage larvae were recovered by the
      Baermann technique after four hours of sedimentation for the counting and
      identification of one hundred larvae per treatment. For each treatment were
      realized 10 repetitions. The average of EPG of Strongylida Order was 630. The
      average of the larvae number obtained in 20 grams of feces and the percentage of
      recovery in the different substrates based on the EPG was: P. taeda treated, 2719
      (22.66%) and not treated, 2353 (20.08%); P. elliotti treated, 3069 (22.48%) and
      not treated, 3181 (24.54%); A. angustifolia treated, 2370 (18.73%) and not
      treated, 3361 (26.75%). There was no statistic difference in 5% level of
      significance between the averages and the number of larvae in the different
      substrates.

PMID- 17196126
TI  - First record of Amblyomma aureolatum (Pallas, 1772) (Acari: Ixodidae)
      parasitizing Alouatta guariba (Humboldt) (Primata: Atelidae) in southern Brazil.
AB  - A female of Amblyomma aureolatum was found on the howler monkey Alouatta guariba,
      in Cachoeira do Sul, Rio Grande do Sul, Southern Brazil. This is the first record
      of this tick species parasitizing this primate species in Brazil.

PMID- 17196127
TI  - [Record of Dasypus novemcinctus (Mammalia: Xenarthra) parasited by Tunga terasma
      (Siphonaptera: Tungidae) in Alegre, State of Espirito Santo, Brazil].
AB  - During a survey of Mycobacterium leprae in wild armadillos in the State of
      Espirito Santo, thirty-four armadillos were captured in the municipality of
      Alegre (20 degrees 45'S, 41 degrees 29'W, 150m). The armadillos, Dasypus
      novemcinctus were examined by clinical and macroscopic examination. In four
      armadillos (11.7%), were found nodes in the abdomen. The nodules were identified
      as Tunga terasma. This is the first report of T. terasma in D. novemcinctus
      armadillos in the State of Espirito Santo, Brazil.

PMID- 17196128
TI  - [Changes of immunocytes in livers of chronic hepatitis C patients treated with
      IFN alpha-2b and ribavirin].
AB  - OBJECTIVE: To investigate the immunocytodynamic changes in the livers of chronic
      hepatitis C patients treated with IFN alpha-2b and ribavirin and to find new
      bases for an effective immune regulation therapy. METHODS: Forty-two chronic
      hepatitis C patients were treated with combined IFN alpha-2b and ribavirin and
      their peripheral blood and liver tissues were collected before the treatment for
      analyses. After the treatment, peripheral blood and liver tissue specimens were
      obtained from only 11 patients. All the specimens were exposed to three
      monoclonal antibody fluorescence dyes, and the CD45+ cells with triple colors
      were analyzed using flow cytometry. RESULTS: Compared to the control groups, the
      positive rates of CD56+, CD57+, CD161+ cells in the livers of those with chronic
      hepatitis C sharply decreased (Probability value less than 0.01), and CD56+T
      cells had decreased mildly; CD28 from the CD56+T cells decreased mildly, but the
      expression of CD152 increased (P<0.05); the positive rates of CD83+CD1a+ cells
      had decreased mildly, and the positive rates of CD80+CD11c+ and the CD86+CD11c+
      cells significantly decreased (P<0.01). After the treatment, the CD56+, CD161+,
      CD56+T, CD161+T, CD80+CD11c+, CD86+CD11c+ cells in the responding group
      increased. CONCLUSION: Combined interferon alpha-2b and ribavirin treatment can
      improve the suppressed cell immunity function.

PMID- 17196129
TI  - [A virological response study of serum leptin level and insulin resistance on the
      antivirus effect in patients with chronic hepatitis C].
AB  - OBJECTIVE: To study the serum leptin level and insulin resistance on sustained
      virological response (SVR) in patients with chronic hepatitis C and to evaluate
      whether serum leptin level and insulin resistance are independent risk factors.
      METHODS: Forty chronic hepatitis C patients were treated with interferon (alpha
      2a) 5 MU and ribavirin 1.0 g for 24 weeks. The fasting serum leptin, insulin,
      glucose, HCV RNA load, alanine aminotransferase (ALT), and aspartate
      aminotransferase (AST) were measured and the insulin resistance index (HOMA-IR:
      homeostasis model of assessment) and body mass index (BMI) were calculated.
      Statistical methods used were univariate analyses and multivariable regression
      analyses. RESULTS: Of the 40 patients, 23 patients (57.5%) had a sustained
      virological response and 17 patients (42.5%) had a non-sustained virological
      response. Patients with a sustained virological response had lower serum leptin,
      HOMA-IR and BMI. Their SVR was associated with age, HCV RNA loads, serum leptin
      level, and insulin resistance, when analyzed with univariate analyses. SVR was
      not associated with sex, ALT, or AST. With multivariable regression analyses,
      serum leptin level and insulin resistance were found to be independent prediction
      factors for SVR in chronic hepatitis C patients with antivirus treatment.
      CONCLUSION: Serum leptin level and insulin resistance were associated with SVR in
      chronic hepatitis C patients; they were independent prediction factors for SVR.

PMID- 17196130
TI  - [Antigenicity of hepatitis C virus F protein and serum prevalence of anti-F in
      HCV-infected patients].
AB  - OBJECTIVE: To examine the antigenicity of hepatitis C virus (HCV) F protein and
      investigate serum prevalence of anti-F in HCV-infected patients. METHODS: Eleven
      pairs of overlapping primers were used to synthesize the full-length HCV f gene,
      from which the truncated HCV f65 gene fragment was amplified by PCR. HCV f65 gene
      was then cloned into pET32a(+), and transformed into E. coli strain Plyss (DE3).
      This recombinant E.coli was induced by IPTG for the production of HCV F65
      protein. The expressed HCV F65 protein, purified by Ni-NTA agarose, was further
      used in ELISA to detect serum anti-F, and to immunize rabbits for making
      polyclonal anti-F. The rabbit polyclonal anti-F was purified by Staphylococcus
      aureus protein A agarose. RESULTS: After recombinant pET32a(+)-f65 was
      constructed successfully, HCV F65 protein was expressed and purified. The
      purified HCV F65 protein was used as a capture antigen in ELISA to detect serum
      anti-F in HCV infected patients (n = 30). The result showed that the mean A450
      value and the positive rate of serum anti-F were 0.125+/-0.061 and 63.3%,
      respectively. The rabbit-derived polyclonal anti-F reacted specifically with HCV
      F65 protein, of which the titer was 1:30,000. CONCLUSION: Our expressed HCV F65
      protein is of antigenicity, and can be used to determine serum anti-F. Anti-F IgG
      does exist in the sera of the HCV-infected patients. Moreover, the rabbit-derived
      polyclonal anti-F can be used to detect HCV F protein.

PMID- 17196131
TI  - [Effect of HCV NS5A on STAT1 phosphorylation and nuclear translocation induced by
      IFN alpha-2b].
AB  - OBJECTIVE: To study the effect of HCV NS5A on the Janus kinase (JAK)/signal
      transducer and activation of transcription (STAT1) phosphorylation and
      translocation induced by IFN alpha-2b and to understand the possible molecular
      mechanism of HCV interferon resistance. METHODS: Hepatocellular carcinoma cell
      line Huh7 was transiently transfected with HCV NS5A protein expression plasmid
      pCNS5A and blank plasmid pRC/CMV respectively; the cells of the same cell line,
      without transfection, served as controls. Immunocytochemistry was used to prove
      the successful transfection. Immunofluorescence and Western blot were performed
      to observe the difference in STAT1 phosphorylation and nuclear translocation
      between HCV NS5A-expressed and non-HCV NS5A-expressed cells after 30 minutes of
      IFN alpha-2b induction. RESULTS: HCV NS5A protein was detected in the cytoplasm
      of Huh7 cells transfected with pCNS5A, indicating the successful transfection. In
      comparison to the blank plasmid-transfected and non-transfected group, STAT1
      phosphorylation and sequential nuclear import were reduced in the presence of HCV
      NS5A protein. CONCLUSION: HCV NS5A can, to some extent, inhibit phosphorylation
      and nuclear translocation of STAT1 in IFN alpha-2b-induced JAK/STAT pathway,
      which may be a possible mechanism of HCV interferon resistance.

PMID- 17196132
TI  - [A clinical study of adefovir dipivoxil, made in China, for treatment of
      hepatitis B e antigen-positive patients with chronic hepatitis B].
AB  - OBJECTIVE: To evaluate the efficacy and safety of a China made adefovir dipivoxil
      (ADV) treatment for hepatitis B e antigen-positive patients with chronic
      hepatitis B. METHODS: Two hundred and thirty patients with chronic hepatitis B
      who were positive for hepatitis B e antigen (HBeAg) were randomly put into groups
      A or B, and 58 patients with lamivudine-resistant chronic hepatitis B were
      randomly put into groups C or D. During the first 12 weeks of the trial, 112
      patients in group A and 115 patients in group B received 10 mg of ADV and a
      placebo once a day; 28 patients in group C received 100 mg of lamivudine (LMV)
      and 10 mg of ADV; 29 patients in group D received 100 mg of LMV and a placebo
      once a day. In the second trial period, all patients received ADV for 36 weeks.
      The primary checking criterion was the serum HBV DNA change during the treatment.
      The secondary ones were alanine aminotransferase (ALT) normalization, HBeAg loss,
      and HBeAg seroconversion. RESULTS: At week 12, the median serum hepatitis B virus
      (HBV) DNA level of group A (ADV-ADV) was reduced 2.8 log10 copies/ml,
      significantly greater than that of group B (placebo-ADV) of 0.3 log10 copies/ml
      reduction (P = 0.000). At week 48, the median serum HBV DNA level of group A and
      group B were reduced 3.6 and 3.4 log10 copies/ml respectively. At week 12, the
      median serum HBV DNA level of group C (LMV+ADV) was reduced 3.0 log10 copies/ml,
      significantly greater than that of the group D (LMV+placebo) of 0.16 log10
      copies/ml reduction (P = 0.000). At week 48, the median serum HBV DNA level of
      group C and group D were reduced 3.6 and 3.8 log10 copies/ml respectively. Only
      5.56% (16/288) patients had adverse events that were mild to moderate. There was
      no significant difference in the change of serum creatinine compared with their
      baseline levels. CONCLUSION: In our HBeAg positive lamivudine-resistant chronic
      hepatitis B patients, 48 weeks of ADV treatment was safe and resulted in
      significant virological and biochemical improvements.

PMID- 17196134
TI  - [A study of chronic hepatitis B infection superinfected with hepatitis E
      infection].
AB  - OBJECTIVES: To compare the influence of hepatitis E virus (HEV) infection on the
      replication of hepatitis B virus (HBV) by observing clinical features, the
      relationship between the number of HBV DNA copies in serum, the degree of hepatic
      function impairments and prognosis of chronic hepatitis B patients with hepatitis
      E superinfection. METHODS: One hundred and fifteen chronic hepatitis B (CHB)
      patients and 115 CHB patients with hepatitis E (HE) superinfection were studied
      and compared. 74 liver tissue biopsy samples of the CHB and 51 of the CHB-HE
      sufferers were obtained. HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HBc
      IgG, anti-HBc-IgM, HBV DNA and anti-HEVIgM were detected respectively by enzyme
      linked immunosorbent assay and polymerase chain reaction. RESULTS: The number of
      HBV DNA copies in sera in the CHB-HE group and the severity of the clinical
      features were significantly higher than those in the CHB group. The former group
      had a poorer prognosis with a 49.6% occurrence rate of severe hepatitis and a
      25.2% death rate while in the latter group the corresponding rates were just 4.4%
      and 1.7%. CONCLUSION: Re-infection with HEV, in those CHB patients, severely
      damaged their hepatic functions and increased their mortality; the older the
      patient and the higher the level of HBV DNA, the poorer the prognosis.

PMID- 17196133
TI  - [Optimal lamivudine treatment duration and the relationship between its early
      response and long term effect].
AB  - OBJECTIVE: To investigate the relationship between the method of administration
      of lamivudine and the therapeutic effect of the treatment in patients with
      chronic hepatitis B virus (HBV) infection. METHODS: One hundred and seventy-nine
      patients were given lamivudine 100 mg daily for 1 to 3 years. The relationships
      of the therapeutic effect and the early response, YMDD mutants and duration of
      treatment were analyzed. RESULTS: Alanine aminotransferase normalization rate,
      the negativity rate of HBV DNA and HBeAg, and HBeAg sero-conversion all were
      increased gradually with prolonged treatment. At the end of 1 year, HBV DNA
      negativity rate (57.0%) reached its peak, HBeAg negativity rate (39.7%) and HBeAg
      sero-conversion rate (16.8%) were higher than those at the end of 3 months (chi2
      = 28.489, 33.238, 12.690, P<0.01). The lower the HBV DNA level was at the end of
      3 months, the higher the HBV DNA negativity and HBeAg sero-conversion rates were
      at the end of 52 weeks and at the end of the 6 months follow-up. When the
      duration of treatment reached 1 year and 1.5 years, HBV DNA rebound rate in the
      patients (40.0% and 40.0% respectively) with HBeAg sero-conversion was obviously
      less (chi2 = 12.424, 10.237, P<0.01) than in those without sero-conversion (88.2%
      and 85.0% respectively). CONCLUSION: Lamivudine therapy for HBV infection is safe
      and effective. The optimal duration of treatment was 1.5 years. The early
      responders had better therapeutic effects. HBV DNA positivity persisting at the
      end of 3 months medication or no HBeAg sero-conversion in 1 year predicts poor
      therapeutic effects.

PMID- 17196136
TI  - [The effects of angiotensin II on gene expression of hepatic stellate cells].
AB  - OBJECTIVE: Our previous investigation demonstrated that angiotensin II could
      induce proliferation and differentiation of hepatic stellate cells, and also
      could up-regulate its extracellular matrix synthesis. The objective of this study
      was to determine the effects of 10(-5) mol/L angiotensin II on gene expression of
      hepatic stellate cells. METHODS: After incubation with 10(-5) mol/L angiotensin
      II for 48 hours, the cultured hepatic stellate cells were collected. The mRNA and
      total protein were obtained from cell lysate and then suppression subtractive
      hybridization (SSH), 2D-gel electrophoresis and MALDI-TOF mass spectrometry were
      used to identify these cDNAs and proteins. RESULTS: A total of 36 clones from the
      subtracted cDNA library were sequenced and compared to sequences in the GenBank
      using BLAST. Of the 36 differentially expressed gene fragments from the
      subtracted library, 13 differentially expressed gene fragments showed significant
      homology to other known proteins, such as ribosomal protein, beta-actin FE-3,
      leucyl-tRNA synthetase, CD147, pyruvate kinase, peroxiredoxin 1, and BAT3, while
      2 other gene fragments encoding protein BC097361 and BC057380 and their functions
      were not disclosed. About 1110 and 1008 protein spots were detected by employing
      the ImageMaster 2D Platinum 4.9 proteome image analysis system in angiotensin
      treated hepatic stellate cells and control cells separately. Among these spots
      108 proteins were up-regulated while the other 153 proteins were down-regulated.
      Several up-regulated proteins were chosen to be excised and in-gel digest MALDI
      TOF-MS and Database analysis showed that among the high expression proteins,
      there were prohibitin, RBL-NDP kinase 1.8x10(4) subunit, electron transfer
      flavoprotein alpha-subunit, guanine nucleotide binding protein, alpha 15, and
      heat shock 7.0x10(4) protein 5. CONCLUSION: Our results suggest that the up
      regulation of hepatic stellate cell mRNA influences proliferation,
      differentiation and apoptosis of those cells. The proteins of signal
      transduction, metabolizing regulation, apoptosis suppression, and fibrogenesis
      regulation of hepatic stellate cells were up-regulated.

PMID- 17196137
TI  - [Direct sequencing and analysis of exons of Wilson' disease gene with the most
      mutations: a study in Hunan Han patients].
AB  - OBJECTIVE: To detect hot point mutations of ATP7B gene in Hunan Han patients with
      Wilson' disease (WD). METHODS: The genomic DNA of 22 WD patients was extracted
      and exons 5, 8, 12, 13 were amplified by PCR. Screening for the mutations was
      done by direct sequencing and analysed by BLAST. RESULTS: Fifteen of the 22
      patients were found with mutations. Ten heterozygous Arg778Leu (2273G --> T)
      mutations were found in exon 8, all of them were accompanied with 2250C --> G
      polymorphism (Leu770Leu). Seven patients were found with 2855G --> A (Arg952Lys)
      polymorphism (4 heterozygous and 3 homozygous), 3 of them had Arg778Leu mutation
      in exon 8 and one with heterozygous mutation Gly943Asp (2828G --> A) in exon 12
      simultaneously. Only one patient was found with heterozygous Pro992Leu (2975C -->
      T) mutation in exon 13. No mutations were found in exon 5. CONCLUSION: Arg778Leu
      is the hot point mutation of ATP7B gene in Hunan Han patients with Wilson'
      disease while exon 5 is not.

PMID- 17196135
TI  - [Dynamic characteristics of SARA during liver fibrogenesis in rats].
AB  - OBJECTIVES: To investigate the dynamic characteristics of Smad anchor for
      receptor activation (SARA) expression during liver fibrogenesis in rats and the
      relationship between SARA and liver fibrosis. METHODS: Liver fibrosis was induced
      in 74 rats by intraperitoneal injection of dimethylnitrosamine (DMN) with a
      dosage of 10 microl/kg body weight, once a day, 3 days per week for 4 weeks. The
      model rats were randomly divided into 9 groups for studying the changes: 1 d, 3
      ds, 1 week, 2 weeks, 3 weeks and 4 weeks after starting the ip injections
      (intoxicating phase), and 1 week, 2 weeks and 4 weeks after stopping the
      injections (5th w, 7th w and 8th w, recovery phase). Each group included 5 to 8
      rats. In addition, 10 non-treated rats served as normal controls. The rat liver
      tissues were examined. Collagen deposition was stained with Sirius red, and
      hydroxyproline (Hyp) was measured with Jamall' method. SARA spatial expression in
      the livers was detected by immunohistochemistry, and the expressions of TGFbeta1,
      alpha-SMA and SARA protein were detected by Western blot. The relationships of
      SARA with Hyp, TGFbeta1 and alpha-SMA were analyzed. RESULTS: During the
      intoxicating phase, the rat hepatic collagen production (Hyp content) and
      deposition increased as DMN intoxication continued, and there was marked fibrous
      septum and pseudo-lobule formation at the end of the 4th w. During the recovery
      phase, the rat hepatic collagen deposition and fibrous septum formation were
      lessened, but the Hyp content in the livers of the model rats at the end of 4th
      w, 5th w, 6th w and 8th w was still higher than that of the controls (193.04+/
      39.15, 188.49+/-39.92, 174.39+/-21.22, 163.59+/-31.47 vs 125.64+/-19.51; t from
      3.43 to 4.9, P<0.01). SARA was mainly stained positively in interstitial cells
      surrounding the hepatic sinusoids in both normal and fibrotic livers, and the
      number of the positive stained cells decreased as liver fibrosis developed, and
      gradually returned to normal after stopping the intoxication. The expressions of
      TGFbeta1 and alpha-SMA were gradually increased, as shown with Western blot, but
      SARA decreased as liver fibrosis developed. The expressions of TGFbeta1 and alpha
      SMA were slightly decreased, SARA expression recovered to the normal level after
      stopping the DMN intoxication. During liver fibrosis developing and recovery
      phases, SARA was significantly negatively correlated with TGFbeta1 and alpha-SMA
      expressions and Hyp contents. CONCLUSIONS: SARA was mainly expressed in the liver
      interstitial cells, and it was negatively correlated with liver fibrosis
      formation.

PMID- 17196138
TI  - [The effectiveness of endoscopic variceal ligation in patients with different
      grades of liver function].
AB  - OBJECTIVE: To evaluate the effectiveness of endoscopic variceal ligation (EVL) in
      patients with different grades of liver function. METHODS: MELD scores were
      determined for 156 patients before their EVL operations. After the EVL these
      patients were followed-up and their survival rates were analyzed. RESULTS: Fifty
      percent of the patients whose MELDs were less than or equal to 7 survived longer
      than 45 months after the EVL; in those with MELDs between 7 and 9, 50% of the
      patients survived 47.34 months; however, the figure for those whose MELD were
      more than 9 survived only 24.89 months. In the first two groups, 50% of the
      patient' survival duration was significantly longer than that of the third group.
      The difference was statistically significant. CONCLUSION: EVL becomes an
      effective clinical way to treat hemorrhage of esophagus varicose veins. The
      survival rate for this procedure is directly correlated with the liver function
      of the patient before the EVL.

PMID- 17196140
TI  - [The importance of using ribavirin in treating chronic hepatitis C].

PMID- 17196139
TI  - [Using vein grafts in living donor liver transplantation].
AB  - OBJECTIVE: To study the use of vein grafts in adult-to-adult (AA) living donor
      liver transplantation (LDLT), we transplanted recipient vena saphena magna grafts
      for drainage of the paramedian portion of the right lobe liver grafts without a
      middle hepatic vein in LDLT. METHODS: From January 2002 to March 2006, 26
      patients underwent A-A LDLT, and recipient saphenous vein grafts were used for
      revascularization of veins and arteries such as: tributaries of the middle
      hepatic vein from V5, V8; right inferior hepatic vein; injured portal vein; and
      hepatic artery. RESULTS: Total outflow reconstruction ratio of V5, V8 and right
      inferior hepatic vein was 76.9% (20/26), the ratio of one-vein reconstruction was
      57.7%, and the ratio of two-vein reconstruction was 19.2%. Reconstruction
      patterns and cases were demonstrated as follows: V5 (n=3), V8 (n=2), V5 and V8
      (n=3), V5 and right inferior hepatic vein (n=1), V8 and right inferior hepatic
      vein (n=1), right inferior hepatic vein (n=10), injured portal vein of the donor
      (n=1). Total ratio of hepatic artery bypass grafting was 11.5% (3/26),
      anastomosis between hepatic artery and abdominal aorta (n=2), and anastomosis
      between hepatic artery and hepatic artery (n=1). Doppler ultrasound showed no
      thrombosis and the blood flowed smoothly and without venous outflow obstruction
      during the 2 to 48 months follow-up period. CONCLUSION: Reconstruction of V5 or
      V8 outflow and hepatic artery bypass grafting using vena saphena magna of the
      recipients can provide sufficient venous outflow and prevent the small-for-size
      syndrome and solve hepatic artery complications. This approach can be
      recommended.

PMID- 17196141
TI  - [Individualizing HCV hepatitis therapy and improving patient's prognosis].

PMID- 17196142
TI  - [Advances in research of antiviral agents for hepatitis C].

PMID- 17196143
TI  - [A liver pathology checked ultrasonographic semi-quantitative scoring system for
      diagnosing compensated liver cirrhosis in patients with CHB].

PMID- 17196144
TI  - [The effects of dendritic cells, transfected with full length wild type p53 and
      modified by liver cancer peptide, on immune responses].

PMID- 17196145
TI  - [Detection of the granulysin expression in patients with primary biliary
      cirrhosis and its clinical significance].

PMID- 17196146
TI  - [Effect of carnosine on prevention of reperfusion liver injury during hemorrhagic
      shock and reperfusion in rats].

PMID- 17196147
TI  - [The effect of HBx gene on the apoptosis of hepatic cells and its possible
      mechanism].

PMID- 17196148
TI  - [Study on autoimmune hepatitis associated genes by human genome oligonucleotide
      microarray].

PMID- 17196149
TI  - [A brief report from "The 57th Annual Meeting of the American Association for the
      liver diseases"].

PMID- 17196150
TI  - [Effect of adiponectin on nonalcoholic fatty liver disease].

PMID- 17196151
TI  - [The use of antigenic epitope in screening for HCV infection].

PMID- 17196152
TI  - [Progress in the treatment of chronic hepatitis B with Telbivudine].

PMID- 17196154
TI  - Exogenous spatial cueing modulates subliminal masked priming.
AB  - An experiment combined exogenous spatial cueing with masked repetition priming.
      The task consisted of an alphabetic decision task (letter/pseudo-letter
      classification) with central targets and peripheral primes that were preceded by
      a valid or invalid spatial cue in the form of an exogenous abrupt onset. In an
      analysis including only participants who were not aware of prime stimuli,
      exogenous location cueing was found to reliably modulate the size of unconscious
      priming effects. These findings suggest that in early vision the exogenous cue
      boosts the signal at the location of the cue resulting in a higher gain for the
      subliminal prime. Our findings therefore suggest that exogenous cueing can affect
      the first feedforward sweep of information through the brain, a processing stream
      which is considered to be automatic and unconscious.

PMID- 17196153
TI  - Spatially mediated capacity limits in attentive visual perception.
AB  - Modern theories conceptualize visual selective attention as a competition between
      objects for the control of cortical receptive fields (RFs). Implicit in this
      framework is the suggestion that spatially proximal objects, which draw from
      overlapping pools of RFs, should be more difficult to represent in parallel and
      with excess capacity than spatially separated objects. The present experiments
      tested this prediction using analysis of response time distributions in a
      redundant-targets letter identification task. Data revealed that excess-capacity
      parallel processing is possible when redundant targets are widely separated
      within the visual field, but that capacity is near fixed when targets are
      adjacent. Even at the largest separations tested, however, processing capacity
      remained strongly limited.

PMID- 17196155
TI  - Quantification of particle-bubble interactions using atomic force microscopy: A
      review.
AB  - The attachment of particles to bubbles in solution is of fundamental importance
      to several industrial processes, most notably in the process of froth flotation.
      During this process hydrophobic particles attach to air bubbles in solution,
      which allows them to be separated as froth at the surface. The addition of
      chemicals can help to modulate these interactions to increase the yield of the
      minerals of interest. Over the past decade the atomic force microscope (AFM) has
      been adapted for use in studying the forces involved in the attachment of single
      particles to bubbles in the laboratory. This allows the measurement of actual
      DLVO (Derjaguin, Landau, Vervey and Overbeek) forces and adhesive contacts to be
      measured under different conditions. In addition contact angles may be calculated
      from features of force versus distance curves. It is the purpose of this article
      to illustrate how the colloid probe technique can be used to make single particle
      bubble interactions and to summarise the current literature describing such
      experiments.

PMID- 17196156
TI  - Optimized dyeing conditions of immunoprotein with reactive dye Procion Blue MX
      7RX.
AB  - For investigating the feasibility of using reactive dyes as an immunoassay
      marker, a dichlorine triazine dye, Procion Blue MX-7RX, was employed to stain the
      antibody against human serum albumin (anti-HSA). With the color intensity
      revealed in the immunochromatographic test strip as the objective variables, the
      optimal dyeing conditions were found as follows: pH 11.4, temperature 35.7
      degrees C, molar ratio 188 (mol dye/mol antibody), and reaction time 45.6 min.
      The dyed-anti-HSA revealed a maximal color intensity of 8738 without apparent
      loss of antigen binding affinity.

PMID- 17196158
TI  - Escherichia coli glyoxalase II is a binuclear zinc-dependent metalloenzyme.
AB  - Cytotoxic methylglyoxal is detoxified by the two-enzyme glyoxalase system.
      Glyoxalase I (GlxI) catalyzes conversion of non-enzymatically produced
      methylglyoxal-glutathione hemithioacetal into its corresponding thioester.
      Glyoxalase II (Glx II) hydrolyzes the thioester into d-lactate and free
      glutathione. Glyoxalase I and II are metalloenzymes, which possess mononuclear
      and binuclear active sites, respectively. There are two distinct classes of GlxI;
      the first class is Zn2+-dependent and is composed of GlxI from mainly eukaryotic
      organisms and the second class is composed of non-Zn2+-dependent (but Ni2+ or
      Co2+-dependent) GlxI enzymes (mainly prokaryotic and leishmanial species). GlxII
      is typically Zn2+-activated, containing Zn2+ and either Fe3+/Fe2+ or Mn2+ at the
      active site depending upon the biological source. To address whether two classes
      of GlxII might exist, glyoxalase II from Escherichia coli was cloned and
      overexpressed and characterized. Unlike E. coli GlxI, which is non-Zn2+
      dependent, Zn2+ activates the E. coli GlxII enzyme, with no evidence for Ni2+
      metal utilization.

PMID- 17196157
TI  - Removal of C-ring from the CD-ring skeleton of 1alpha,25-dihydroxyvitamin D3 does
      not alter its target tissue metabolism significantly.
AB  - It is now well established that 1alpha,25(OH)2D3 is metabolized in its target
      tissues through the modifications of both side chain and A-ring. The C-24
      oxidation pathway is the side chain modification pathway through which
      1alpha,25(OH)2D3 is metabolized into calcitroic acid. The C-3 epimerization
      pathway is the A-ring modification pathway through which 1alpha,25(OH)2D3 is
      metabolized into 1alpha,25(OH)2-3-epi-D3. During the past two decades, a great
      number of vitamin D analogs were synthesized by altering the structure of both
      side chain and A-ring of 1alpha,25(OH)2D3 with the aim to generate novel vitamin
      D compounds that inhibit proliferation and induce differentiation of various
      types of normal and cancer cells without causing significant hypercalcemia.
      Previously, we used some of these analogs as molecular probes to examine how
      changes in 1alpha,25(OH)2D3 structure would affect its target tissue metabolism.
      Recently, several nonsteroidal analogs of 1alpha,25(OH)2D3 with unique biological
      activity profiles were synthesized. Two of the analogs, SL 117 and WU 515 lack
      the C-ring of the CD-ring skeleton of 1alpha,25(OH)2D3. SL 117 contains the same
      side chain as that of 1alpha,25(OH)2D3, while WU 515 contains an altered side
      chain with a 23-yne modification combined with hexafluorination at C-26 and C-27.
      Presently, it is unknown how the removal of C-ring from the CD-ring skeleton of
      1alpha,25(OH)2D3 would affect its target tissue metabolism. In the present study,
      we compared the metabolic fate of SL 117 and WU 515 with that of 1alpha,25(OH)2D3
      in both the isolated perfused rat kidney, which expresses only the C-24 oxidation
      pathway and rat osteosarcoma cells (UMR 106), which express both the C-24
      oxidation and C-3 epimerization pathways. The results of our present study
      indicate that SL 117 is metabolized like 1alpha,25(OH)2D3, into polar metabolites
      via the C-24 oxidation pathway in both rat kidney and UMR 106 cells. As expected,
      WU 515 with altered side chain structure is not metabolized via the C-24
      oxidation pathway. Unlike in rat kidney, both SL 117 and WU 515 are also
      metabolized into less polar metabolites in UMR 106 cells. These metabolites
      displayed GC and MS characteristics consistent with A-ring epimerization and were
      putatively assigned as C-3 epimers of SL 117 and WU 515. In summary, we report
      that removal of the C-ring from the CD-ring skeleton of 1alpha,25(OH)2D3 does not
      alter its target tissue metabolism significantly.

PMID- 17196159
TI  - A comparison of individual and group cognitive-behavioural treatment for female
      pathological gambling.
AB  - The current study aimed to determine the differential efficacy of a cognitive
      behavioural treatment program for female pathological gamblers delivered in
      individual and group format. Fifty-six female pathological gamblers with
      electronic gaming machine gambling problems were randomly assigned to the control
      (waiting list) group or one of the treatment groups (individual or group
      treatment). Treatment comprised a 12-session program including financial limit
      setting, alternative activity planning, cognitive correction, problem solving,
      communication training, relapse prevention, and imaginal desensitisation.
      Treatment outcome was evaluated with conceptually related measures within the
      areas of gambling behaviour and psychological functioning. While individual and
      group treatment formats generally produced comparable outcomes in terms of
      gambling behaviour and psychological functioning, group treatment failed to
      produce superior outcomes to the control group in relation to several measures of
      psychological functioning. Moreover, by the completion of the six-month follow
      up, 92% of the gamblers allocated to individual treatment compared with 60%
      allocated to group treatment no longer satisfied the diagnostic criteria for
      pathological gambling. These findings suggest that some caution should be
      employed when delivering cognitive-behavioural treatment in a group format until
      further research is conducted to establish its efficacy.

PMID- 17196160
TI  - The role of nitric oxide in delta-aminolevulinic acid (ALA)-induced
      photosensitivity of cancerous cells.
AB  - Application of delta-aminolevulinic acid (ALA) results in the endogenous
      accumulation of protoporphyrin IX and is a useful approach in the photodynamic
      therapy (PDT) of cancers. To investigate the role of nitric oxide (NO) in the
      specific accumulation of protoporphyrin and ALA-induced PDT of cancerous cells,
      we transfected inducible-nitric oxide synthase (NOS2) cDNA into human embryonic
      kidney (HEK) 293T cells and examined the ALA-induced photo-damage as well as the
      accumulation of porphyrin in the cells. When the NOS2-expressing HEK293T cells
      were treated with ALA and then exposed to visible light, they became more
      sensitive to the light with accumulating porphyrins, as compared with the ALA
      treated control cells. An increase in the generation of NO in transfected cells
      led to the accumulation of protoporphyrin with a concomitant decrease of
      ferrochelatase, the final step enzyme of heme biosynthesis. When mouse macrophage
      like RAW264.7 cells were cultured with lipopolysaccharide and interferon-gamma,
      the expression of NOS2 was induced. The addition of ALA to these cells led to the
      accumulation of protoporphyrin and cell death upon exposure to light. The
      treatment of cells with an NOS inhibitor, NG-monomethyl-L-arginine acetate,
      resulted in the inhibition of protoporphyrin accumulation and cell death. The
      levels of mitochondrial ferrochelatase and rotenone-sensitive NADH dehydrogenase
      in the NOS2-induced cells decreased. These results indicated that the generation
      of NO augments the ALA-induced accumulation of protoporphyrin IX and subsequent
      photo-damage in cancerous cells by decreasing the levels of mitochondrial iron
      containing enzymes. Based on the fact that the production of NO in cancerous
      cells is elevated, NO in the cells is responsible for susceptibility with ALA
      induced PDT.

PMID- 17196161
TI  - KLF6 and HSF4 transcriptionally regulate multidrug resistance transporters during
      inflammation.
AB  - Endotoxin-induced inflammation alters the hepatic expression of the drug efflux
      transporter genes mdr1b (Abcb1b) and mrp3 (Abcc3) in rats. In this study, we
      identified a novel kruppel-like zinc finger protein 6 (KLF6) cis-element on the
      rat mdr1b promoter which is important for basal activity and IL-1beta and
      endotoxin-mediated induction in gene transcription. Interestingly, KLF6 also
      functioned as a negative transcriptional regulator, inhibiting TNF-alpha-mediated
      induction of mdr1b. Furthermore, novel CCAAT/enhancer binding protein beta
      (C/EBPbeta) and heat shock factor 4 (HSF4) transcription binding sites were
      identified on the rat mrp3 promoter. Deletion of the HSF4 element significantly
      increased transcriptional activity of the mrp3 gene when exposed to TNF-alpha.
      Endotoxin treatment significantly affected transcriptional activity only in
      C/EBPbeta and HSF4 double deletion mrp3 promoter constructs. In summary, KLF6 and
      HSF4 are stimuli-specific regulatory elements which may be important in the
      control of the rat mdr1b and mrp3 genes during health and disease.

PMID- 17196162
TI  - Mist1-null mice are resistant to streptozotocin-induced beta cell damage.
AB  - Streptozotocin (STZ), a pancreatic beta cell toxin, is used to induce diabetic
      conditions by targeting the Glut-2 transporter. We have recently identified
      decreased Glut-2 expression in beta cells of mice lacking the transcription
      factor Mist1 (Mist1(KO)). Given the loss in Glut-2 expression, we examined
      whether Mist1(KO) beta cells have an increased resistance to STZ. Mist1(KO) and
      wild-type (WT) female mice received a single 100 or 200 mg/kg injection of STZ,
      and resting glucose levels and islet morphology were assayed 3-7 days after
      injection. Ten-month-old Mist1(KO) mice have less beta cell damage when exposed
      to high levels of STZ while 2-month-old Mist1(KO) mice exhibit a dose-dependent
      resistance. Surprisingly, Mist1(KO) mice still have elevated fasting glucose
      levels when compared to WT mice. These results suggest that while Mist1(KO)
      islets have increased resistance to STZ, additional effects outside of beta cell
      loss alter blood glucose homeostasis.

PMID- 17196163
TI  - Angiotensin II increases the cholesterol content of foam cells via down
      regulating the expression of ATP-binding cassette transporter A1.
AB  - ATP-binding cassette transporter A1 (ABCA1) as one kind of membrane protein was
      found recently to play a major role in cholesterol homeostasis. Angiotensin II
      (AngII) has been shown to possess several atherogenic properties. The aim of the
      study is to investigate the influence of AngII on the expression of ABCA1 and the
      content of cholesterol in THP-1 derived foam cells. Our study showed that: (1)
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting
      demonstrated that AngII down-regulated the expression of ABCA1 in a dose
      dependent manner. (2) The content of cholesterol was negatively correlated with
      ABCA1. The results suggest the promoting effects of AngII on the forming of foam
      cells are in a dose-dependent manner via down-regulating the expression of ABCA1.

PMID- 17196164
TI  - Synthesis of ATP by the simple addition of ADP to the p-nitrophenyl phosphate
      prepared phosphoenzyme of the sarcoplasmic reticulum Ca2+-ATPase.
AB  - The sarcoplasmic reticulum Ca2+-ATPase was phosphorylated with either p
      nitrophenyl phosphate (pNPP) or with ATP in the presence of Ca2+, under the
      condition that the free energy change of pNPP hydrolysis is less than that of
      ATP, DeltaG'(pNPP)<DeltaG'(ATP), or the condition that DeltaG'(pNPP)
      approximately DeltaG'(ATP), without any additional energy input. In both cases,
      the pNPP-prepared phosphoenzyme synthesized ATP upon the simple addition of ADP,
      as did the phosphoenzyme prepared with ATP. The sensitivity of these
      phosphoenzymes to ADP for the synthesis of ATP was the same. In other words,
      there is no hysteresis of the phosphate donor to its DeltaG' value in these
      phosphoenzymes. This result means that both phosphoenzymes by themselves must
      have sufficient conformational energy, independent of the DeltaG' value of the
      phosphate donor, for the reversed synthesis of ATP, because a high-energy
      phosphate donor (ATP) cannot be formed from a lower-energy phosphate donor
      (pNPP).

PMID- 17196165
TI  - Genetically selected stem cells from human adipose tissue express cardiac
      markers.
AB  - In the present study, the potential of human adipose-derived stem cells to
      differentiate into cells with characteristics of cardiomyocytes was investigated.
      Adipose tissue-derived stem cells (ADSCs) were transduced with two different
      lentiviral vectors simultaneously: (1) a lentiviral vector expressing eGFP
      controlled by the Nkx2.5 promoter and (2) a lentiviral vector expressing DsRed2
      controlled by the myosin light chain-2v promoter (MLC-2v). Nkx2.5-eGFP and MLC-2v
      DsRed2 dual positive cells were isolated by FACS. Immunostaining and RT-PCR
      analysis of the dual positive cells revealed that these cells are positive for
      Nkx2.5, cardiac troponin I, and L-type calcium channel alpha-1c subunit.
      Electrophysiology studies demonstrated the presence of functional voltage
      dependent calcium and potassium channels. These observations confirm that cardiac
      progenitor cells can be isolated and enriched from human adipose-derived stem
      cells using lentiviral selection, and they might represent a new source for cell
      therapy for myocardial infarction and heart failure.

PMID- 17196166
TI  - Ischemia promotes calpain-mediated degradation of p120-catenin in SH-SY5Y cells.
AB  - p120-catenin contributes to the cadherin-mediated adhesion and aggregation of
      cells. mu-Calpain was activated and p120-catenin was degraded after 36 h of
      ischemia in differentiated SH-SY5Y cells. Calpain inhibitors Cbz-Val-Phe-H
      (MDL28170, 20 microM) and N-acetyl-leucyl-leucyl-norleucinal (ALLN, 20 microM)
      increased the levels of dephosphorylated p120-catenin, aggregation, and cell
      survival as detected by reduced LDH release in ischemic cells. However, a
      proteasome inhibitor lactacystin had no such effects. This is the first report of
      the calpain-mediated degradation of p120-catenin and an association between the
      level of dephosphorylated p120-catenin and cell aggregation in ischemic neuronal
      cells.

PMID- 17196167
TI  - Intracellular signaling via ERK/MAPK completes the pathway for tubulogenic
      fibronectin in MDCK cells.
AB  - A classic in vitro model of branching morphogenesis utilizes the Madin-Darby
      canine kidney (MDCK) cell line. MDCK Strain II cells form hollow monoclonal cysts
      in a three-dimensional collagen matrix over the course of 10 days and tubulate in
      response to hepatocyte growth factor (HGF). We and our colleagues previously
      showed that activation of the extracellular-signal regulated kinase (ERK, aka
      MAPK) pathway is necessary and sufficient to induce tubulogenesis in MDCK cells.
      We also showed in a microarray study that one of the genes upregulated by HGF was
      the known tubulogene fibronectin. Given that HGF activates a multitude of
      signaling pathways, including ERK/MAPK, to test the intracellular regulatory
      pathway, we used two distinct inhibitors of ERK activation (U0126 and PD098059).
      Following induction of MDCK Type II cells with HGF, tubulogenic fibronectin mRNA
      was upregulated fourfold by real-time PCR, and minimal or no change in
      fibronectin expression was seen when HGF was added with either U0126 or PD098059.
      We confirmed these results using an MDCK cell line inducible for Raf, which is
      upstream of ERK. Following activation of Raf, fibronectin mRNA and protein
      expression were increased to a similar degree as was seen following HGF
      induction. Furthermore, MDCK Strain I cells, which originate from collecting
      ducts and have constitutively active ERK, spontaneously initiate tubulogenesis.
      We show here that MDCK Strain I cells have high levels of fibronectin mRNA and
      protein compared to MDCK Strain II cells. When U0126 and PD098059 were added to
      MDCK Strain I cells, fibronectin mRNA, and protein levels were decreased to
      levels seen in MDCK Strain II cells. These data allow us to complete what we
      believe is the first description of a tubulogenic pathway from receptor/ligand
      (HGF/CMET), through an intracellular signaling pathway (ERK/MAPK), to
      transcription and, finally, secretion of a critical tubuloprotein (fibronectin).

PMID- 17196168
TI  - Oligo(dT) is not a correct native PAGE marker for single-stranded DNA.
AB  - Polyacrylamide gel electrophoresis is a widely used method to study short DNA
      fragments in solution. It is, however, a relative method requiring length markers
      to assess mobility, shape, flexibility, and molecularity of the DNA structures of
      interest. In recent literature we have encountered the use of oligo(dT) fragments
      as the native PAGE length markers. We show here that this practice is inadequate
      because oligo(dT) migration is strongly retarded in native polyacrylamide gels.
      This conclusion is qualitatively true irrespective of the conditions of
      electrophoresis, oligo(dT) length, and gel concentration. Depending on their
      length, oligo(dT) fragments migrate 2--4 times slower than that would correspond
      to their nucleotide number. This leads to erroneous conclusions, e.g.,
      determination of the number of associated molecules in guanine quadruplexes or
      other DNA complexes.

PMID- 17196169
TI  - ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in
      a Ca2+-dependent manner.
AB  - Intracellular localization of the penta-EF-hand Ca2+-binding protein ALG-2 in
      HeLa cells was investigated by immunofluorescent confocal microscopy using a
      polyclonal antibody. In addition to its presence in the nucleus, ALG-2 was found
      to be distributed in a punctate pattern in the cytoplasm, where it was partly co
      stained with an endoplasmic reticulum (ER) exit site marker p125. In vitro GST
      pull down analysis demonstrated that ALG-2 and its alternatively spliced isoform
      interact with the COPII component Sec31A in a Ca2+-dependent manner, and a biotin
      labeled ALG-2 overlay assay revealed direct binding of ALG-2 to Sec31A.
      Biochemical and immunofluorescent microscopic analyses showed that ALG-2 was
      enriched at the Sec31A-localizing membrane compartments upon stimulation with the
      Ca2+ ionophore A23187. In contrast, treatment of cells with the membrane-permeant
      Ca2+ chelator BAPTA-AM led to a dispersion of ALG-2 throughout the cells and to a
      significant loss of Sec31A in the perinuclear region. These findings establish
      Sec31A as a novel target for ALG-2 and provide a framework for studies on the
      roles of ALG-2 in ER-Golgi transport.

PMID- 17196170
TI  - On the use of in vivo cargo velocity as a biophysical marker.
AB  - Molecular motors move many intracellular cargos along microtubules. Recently, it
      has been hypothesized that in vivo cargo velocity can be used to determine the
      number of engaged motors. We use theoretical and experimental approaches to
      investigate these assertions, and find that this hypothesis is inconsistent with
      previously described motor behavior, surveyed and re-analyzed in this paper.
      Studying lipid droplet motion in Drosophila embryos, we compare transport in a
      mutant, Delta(halo), with that in wild-type embryos. The minus-end moving cargos
      in the mutant appear to be driven by more motors (based on in vivo stall force
      observations). Periods of minus-end motion are indeed longer than in wild-type
      embryos but the corresponding velocities are not higher. We conclude that
      velocity is not a definitive read-out of the number of motors propelling a cargo.

PMID- 17196171
TI  - p38MAPK activation is involved in androgen-independent proliferation of human
      prostate cancer cells by regulating IL-6 secretion.
AB  - Increased levels of serum interleukin-6 (IL-6) are frequently observed in
      patients with advanced, hormone-refractory prostate cancer. However, the precise
      mechanism of IL-6 regulation is still largely unknown. Since prostate cancer
      gradually progresses to an androgen-independent state despite the stress caused
      by various therapeutic agents, we hypothesized the stress-activated protein
      kinases (SAPKs) involvement in androgen-independent growth or IL-6 secretion of
      prostate cancer cells. Using PC-3 and DU145 human prostate cancer cells, we
      analyzed the role of SAPKs in IL-6 mediated cell growth and found that the
      p38MAPK and JNK are involved in androgen-independent cancer cell growth.
      Furthermore, IL-6 secretion by PC-3 and DU145 cells was significantly suppressed
      by SAPKs inhibitor, especially by p38MAPK inhibitor SB203580, but not by JNK
      inhibitor SP600125 nor by MEK inhibitor, PD98059. These results raised the
      possibility that the IL-6 mediated androgen-independent proliferation of PC-3 and
      DU145 cells is regulated at least partly via SAPKs signaling pathway especially
      through p38MAPK activation.

PMID- 17196172
TI  - 5-Bromodeoxyuridine induced differentiation of a human small cell lung cancer
      cell line is associated with alteration of gene expression.
AB  - Small cell lung cancer (SCLC) appears to arise from neuroendocrine cells with the
      potential to differentiate into a variety of lung epithelial cell lineages. In
      order to investigate molecular events underlying the cell type transition in
      SCLC, we treated a SCLC cell line H526 with a differentiation inducing agent 5
      bromodeoxyuridine (BrdU). The treatment led to a dramatic conversion from
      suspension cells to adherent cells exhibiting an epithelioid phenotype, which
      remarkably reduced the ability of colony formation in soft agar and suppressed
      the tumor growth rate in nude mice. The phenotypic transition was consistent with
      upregulation of surfactant protein C (SFTPC), thyroid transcription factor 1 (TTF
      1), Connexin 26 (Cx26), insulin-like growth factor binding protein-related
      protein 1 (IGFBP-rP1), as well as homeobox genes LAGY, PITX1, and HOXB2. Our data
      suggest that BrdU induced cell differentiation could be linked to the development
      of a less aggressively phenotype in small cell lung cancer.

PMID- 17196173
TI  - Differential dependence on DNA ligase of type II restriction enzymes: a practical
      way toward ligase-free DNA automaton.
AB  - DNA computing study is a new paradigm in computer science and biological
      computing fields. As one of DNA computing approaches, DNA automaton is composed
      of the hardware, input DNA molecule and state transition molecules. By now
      restriction enzymes are key hardware for DNA computing automaton. It has been
      found that DNA computing efficiency may be independent on DNA ligases when type
      IIS restriction enzymes like FokI are used as hardware. In this study, we
      compared FokI with four other distinct enzymes HgaI, BsmFI, BbsI, and BseMII, and
      found their differential independence on T4 DNA ligase when performing automaton
      reactions. Since DNA automaton is a potential powerful tool to tackle gene
      relationship in genomic network scale, the feasible ligase-free DNA automaton may
      set an initial base to develop functional DNA automata for various DNA technology
      development and implications in genetics study in the near future.

PMID- 17196174
TI  - Inhibition of PI3K and calcineurin suppresses chemoattractant receptor-homologous
      molecule expressed on Th2 cells (CRTH2)-dependent responses of Th2 lymphocytes to
      prostaglandin D(2).
AB  - Interaction of prostaglandin D2 (PGD2) with chemoattractant receptor-homologous
      molecule expressed on Th2 cells (CRTH2) triggers chemotaxis and pro-inflammatory
      cytokine production by Th2 lymphocytes. We have investigated the role of
      inhibitors of various cell-signalling pathways on the responses of human CRTH2+
      CD4+ Th2 cells to PGD2. Phosphatidylinositol 3-kinase (PI3K) and
      Ca2+/calcineurin/nuclear factor of activated T cells (NFAT) pathways were
      activated by PGD2 in Th2 cells in a CRTH2-dependent manner. Inhibition of the
      PI3K pathway with LY294002 significantly reduced both PGD2-induced cell migration
      and cytokine (interleukin-4, interleukin-5 and interleukin-13) production. The
      inhibitory effect of LY294002 on cell migration is likely to be related to
      cytoskeleton reorganization as it showed a similar potency on PGD2-induced actin
      polymerization. The calcineurin inhibitors, tacrolimus (FK506) and cyclosporin A,
      had no effect on cell migration but completely blocked both cytokine production
      and the nuclear translocation of NFATc1 suggesting that Ca2+/calcineurin/NFAT is
      involved in CRTH2-dependent cytokine production but not chemotaxis. The promotion
      of NFAT nuclear location by PI3K activation may be mediated by negative
      regulation of glycogen synthase kinase-3beta (GSK3beta), since the PGD2
      stimulated increase in phospho-GSK3beta was down-regulated by LY294002, and
      inhibition of GSK3beta by SB216763 enhanced PGD2-induced Th2 cytokine production
      and reversed the inhibitory effect of LY294002. These data suggest that PI3K and
      Ca2+/calcineurin/NFAT signalling pathways are critically involved in pro
      inflammatory responses of Th2 cells to PGD2.

PMID- 17196175
TI  - Biochemical and pharmacological characterization of P-site inhibitors on
      homodimeric guanylyl cyclase domain from natriuretic peptide receptor-A.
AB  - Guanylyl cyclases catalyze the formation of cGMP from GTP. This family of enzymes
      includes soluble (sGC) and particulate guanylyl cyclases (pGC). The sGC are
      heterodimers containing one active catalytic site and one inactive pseudo-site.
      They are activated by nitric oxide. The pGC are homodimers whose activity is
      notably regulated by peptide binding to the extracellular domain and by ATP
      binding to the intracellular kinase homology domain (KHD). The catalytic
      mechanism of the pGC is still not well understood. Homology modeling of the
      structure of the homodimeric guanylyl cyclase domain, based on the crystal
      structure of adenylyl cyclase, suggests the existence of two functional sites for
      the substrate GTP. We used a purified and fully active recombinant catalytic
      domain from mammalian pGC, to document its enzyme kinetics properties in the
      absence of the KHD. The enzyme presents positive cooperativity with the substrate
      Mg-GTP. However, a heterodimeric catalytic domain mutant (GC-HET) containing only
      one active catalytic site is non-cooperative and is more similar to sGC.
      Structure-activity studies of purine nucleoside analogs indicate that 2'd3'GMP is
      the most potent inhibitor of pGC tested. It displays mixed non-competitive
      inhibition properties that are potentiated by the second catalytic product
      inorganic pyrophosphate (PPi). It appears to be equivalent to purinergic site (P
      site) inhibitors characterized on particulate adenylyl cyclase. Inhibition of pGC
      by 2'd3'GMP in the presence of PPi is accompanied by a loss of cooperative enzyme
      kinetics. These results are best explained by an allosteric dimer model with
      positive cooperativity for both the substrate and inhibitors.

PMID- 17196176
TI  - Differentiating hemodynamic responses in rat primary somatosensory cortex during
      non-noxious and noxious electrical stimulation by optical imaging.
AB  - Nociception in the primary somatosensory (S1) cortex remains in need of further
      elucidation. The spatiotemporal comparison on changes of the cerebral blood
      volume evoked by graded peripheral electrical stimulation was performed in rat
      contralateral somatosensory cortex with optical intrinsic signal imaging (OISI,
      optical reflectance at 550 nm). Non-noxious electrical stimulus was applied with
      5 Hz pulses (0.5 ms peak duration) for 2 s at the threshold current for muscle
      twitch, while noxious stimulus was delivered at currents of 10x and 20x amplitude
      of the predetermined threshold. Although the dimensions of peak response defined
      in the spatial domain (cerebral blood volume increase) in the S1 cortex presented
      no significant difference under non-/noxious stimuli, its early response
      component (about 1 s after stimulation onset) revealed by OISI technique was
      suggested to differentiate the loci of activated cortical region due to different
      stimulation in this study. The magnitude and duration of the optical intrinsic
      signal (OIS) response was found increasing with the varying stimulus intensity.
      Regions activated by the delivery of a noxious stimulus were surrounded by a ring
      of inverted optical intrinsic signal, the amplitude of that was inversely
      proportional to the strength of the optical signal attributable to activation.
      Intense stimuli significantly augmented the inverted optical signal in magnitude
      and spatial extent. These results indicated that noxious stimulation evoked
      different response patterns in the contralateral S1 cortex. The magnitude
      dependent inverted optical signal might contribute to the differentiation of
      nociceptive input in the S1 cortex.

PMID- 17196178
TI  - Effects of peripheral inflammation on activation of p38 mitogen-activated protein
      kinase in the rostral ventromedial medulla.
AB  - In the present study, the activation of p38 mitogen-activated protein kinase (p38
      MAPK) in the rostral ventromedial medulla (RVM) following the injection of
      complete Freund's adjuvant (CFA) into the rat hindpaw was examined in order to
      clarify the mechanisms underlying the dynamic changes in the descending pain
      modulatory system after peripheral inflammation. Phospho-p38 MAPK-immunoreactive
      (p-p38 MAPK-IR) neurons were observed in the nucleus raphe magnus (NRM) and
      nucleus reticularis gigantocellularis pars alpha (GiA). Inflammation induced the
      activation of p38 MAPK in the RVM, with a peak at 30 min after the injection of
      CFA into the hindpaw, which lasted for 1 h. In the RVM, the number of p-p38 MAPK
      IR neurons per section in rats killed at 30 min after CFA injection (19.4+/-2.0)
      was significantly higher than that in the naive group (8.4+/-2.4) [p<0.05]. At 30
      min after CFA injection, about 40% of p-p38 MAPK-IR neurons in the RVM were
      serotonergic neurons (tryptophan hydroxylase, TPH, positive) and about 70% of TPH
      IR neurons in the RVM were p-p38 MAPK positive. The number of p-p38 MAPK- and TPH
      double-positive RVM neurons in the rats with inflammation was significantly
      higher than that in naive rats [p<0.05]. These findings suggest that inflammation
      induced activation of p38 MAPK in the RVM may be involved in the plasticity in
      the descending pain modulatory system following inflammation.

PMID- 17196177
TI  - Delayed increase of tyrosine hydroxylase expression in rat nigrostriatal system
      after traumatic brain injury.
AB  - Tyrosine hydroxylase (TH) is the key enzyme for synthesizing dopamine (DA) in
      dopaminergic neurons and its terminals. Emerging experimental and clinical
      evidence support the hypothesis of a disturbance in dopamine neurotransmission
      following traumatic brain injury (TBI). However, the effect of controlled
      cortical impact (CCI) injury on TH in the nigrostriatal system is currently
      unknown. To determine if there is an alteration in TH after CCI injury, we
      examined TH levels at 1 day, 7 days, and 28 days post-injury by utilizing a
      commercially available antibody specific to TH. Rats were anesthetized and
      surgically prepared for CCI injury (4 m/s, 3.2 mm) or sham surgery. Injured (N=6)
      and sham animals (N=6) were sacrificed and coronally sectioned (35 microm thick)
      through the striatum and substantia nigra (SN) for immunohistochemistry.
      Additionally, semiquantitative measurements of TH protein in striatal and SN
      homogenates from injured (N=6) and sham (N=6) rats sacrificed at the appropriate
      time post-surgery were assessed using Western blot analysis. TH protein is
      bilaterally increased at 28 days post-injury in nigrostriatal system revealed by
      immunohistochemistry in injured rats compared to sham controls. Western blot
      analysis confirms the findings of immunohistochemistry in both striatum and SN.
      We speculate that the increase in TH in the nigrostriatal system may reflect a
      compensatory response of dopaminergic neurons to upregulate their synthesizing
      capacity and a delayed increase in the efficiency of DA neurotransmission after
      TBI.

PMID- 17196180
TI  - Vasopressin-induced translocation and proteolysis of protein kinase Calpha in an
      amphibian brain: modulation by corticosterone.
AB  - In urodele amphibians, the hypothalamic neuropeptide arginine vasotocin and the
      adrenal steroid corticosterone interact to regulate reproductive behavior by
      actions in the brain. The present study investigated signal transduction pathways
      underlying acute effects of vasotocin and corticosterone, presumably mediated via
      "non-genomic" steroid action, in an amphibian brain. We used Western blot to
      examine the effects of corticosterone and the vasotocin receptor agonist arginine
      vasopressin, alone and in combination, on the subcellular localization and
      proteolytic processing of protein kinase C-alpha (PKCalpha) in tiger salamander
      brain tissue. Treatment of whole brain minces with vasopressin or vasotocin led
      to increases in PKCalpha in membrane fractions and concurrent decreases in
      PKCalpha in cytosolic fractions. Vasopressin or vasotocin treatment also induced
      the appearance in membrane and cytosolic fractions of a PKCalpha-immunoreactive
      band that corresponds to PKMalpha, the proteolytically generated, free catalytic
      subunit of PKCalpha. Treatment with corticosterone alone had no consistent effect
      on either PKCalpha or PKMalpha in either fraction. However, pretreatment with
      corticosterone reliably blocked vasopressin-induced increases in cytosolic
      PKMalpha. These data provide new information about the cellular mechanisms of
      action of vasopressin and corticosterone in the vertebrate brain and suggest a
      cellular mechanism by which the two hormones interact to regulate neuronal
      physiology and behavior.

PMID- 17196179
TI  - Regional expression of NO synthase, NAD(P)H oxidase and superoxide dismutase in
      the rat brain.
AB  - Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) contributes to
      regulation of cerebral circulation, whereas that produced by neuronal NOS (nNOS)
      participates in the regulation of brain function. In particular, NO plays an
      important role in modulation of sympathetic activity and hence central regulation
      of arterial pressure. Superoxide derived from NAD(P)H oxidase avidly reacts with
      and inactivates NO and, thereby, modulates its bioavailability. Calmodulin (CM)
      is required for activation of NOS and soluble guanylate cyclase (sGC) serves as a
      NO receptor. Superoxide is dismutated to H2O2 by superoxide dismutase (SOD) and
      H2O2 is converted to H2O by catalase or glutathione peroxidase (GPX). Given the
      importance of NO in the regulation of brain perfusion and function, we undertook
      the present study to determine the relative expressions of immunodetectable nNOS,
      eNOS, CM, sGC, NAD(P)H oxidase and SOD by Western analysis in different regions
      of the normal rat brain. nNOS was abundantly expressed in the pons cerebellum and
      hypothalamus and less so in the cortex and medulla. sGC abundance was highest in
      the hypothalamus and pons, and lowest in the cerebellum and medulla. eNOS and
      calmodulin were equally abundant in all regions. NAD(P)H oxide was most abundant
      in the pons compared to other regions. Cytoplasmic SOD was equally distributed
      among different regions but catalase and GPX were more abundant in pons,
      hypothalamus and medulla and less so in the cortex and cerebellum. Thus, the
      study documented regional distributions of NOS, NAD(P)H oxidase, antioxidant
      enzymes, sGC and calmodulin which collectively regulate production and biological
      activities of NO and superoxide, the two important small molecular size signaling
      molecules.

PMID- 17196181
TI  - Evaluation of the neuroprotective effect of cannabinoids in a rat model of
      Parkinson's disease: importance of antioxidant and cannabinoid receptor
      independent properties.
AB  - We have recently demonstrated that two plant-derived cannabinoids, Delta9
      tetrahydrocannabinol and cannabidiol (CBD), are neuroprotective in an animal
      model of Parkinson's disease (PD), presumably because of their antioxidant
      properties. To further explore this issue, we examined the neuroprotective
      effects of a series of cannabinoid-based compounds, with more selectivity for
      different elements of the cannabinoid signalling system, in rats with unilateral
      lesions of nigrostriatal dopaminergic neurons caused by local application of 6
      hydroxydopamine. We used the CB1 receptor agonist arachidonyl-2-chloroethylamide
      (ACEA), the CB2 receptor agonist HU-308, the non-selective agonist WIN55,212-2,
      and the inhibitors of the endocannabinoid inactivation AM404 and UCM707, all of
      them administered i.p. Daily administration of ACEA or WIN55,212-2 did not
      reverse 6-hydroxydopamine-induced dopamine (DA) depletion in the lesioned side,
      whereas HU-308 produced a small recovery that supports a possible involvement of
      CB2 but not CB1 receptors. AM404 produced a marked recovery of 6-hydroxydopamine
      induced DA depletion and tyrosine hydroxylase deficit in the lesioned side.
      Possibly, this is caused by the antioxidant properties of AM404, which are
      derived from the presence of a phenolic group in its structure, rather than by
      the capability of AM404 to block the endocannabinoid transporter, because UCM707,
      another transporter inhibitor devoid of antioxidant properties, did not produce
      the same effect. None of these effects were observed in non-lesioned
      contralateral structures. We also examined the timing for the effect of CBD to
      provide neuroprotection in this rat model of PD. We found that CBD, as expected,
      was able to recover 6-hydroxydopamine-induced DA depletion when it was
      administered immediately after the lesion, but it failed to do that when the
      treatment started 1 week later. In addition, the effect of CBD implied an
      upregulation of mRNA levels for Cu,Zn-superoxide dismutase, a key enzyme in
      endogenous defenses against oxidative stress. In summary, our results indicate
      that those cannabinoids having antioxidant cannabinoid receptor-independent
      properties provide neuroprotection against the progressive degeneration of
      nigrostriatal dopaminergic neurons occurring in PD. In addition, the activation
      of CB2 (but not CB1) receptors, or other additional mechanisms, might also
      contribute to some extent to the potential of cannabinoids in this disease.

PMID- 17196182
TI  - The immunolocalization of the synaptic glycoprotein neuroplastin differs
      substantially between the human and the rodent brain.
AB  - Neuroplastin is a cell adhesion molecule of the immunoglobulin superfamily that
      exists in two splice isoforms, np65/np55, and that was reported to play a
      prominent role in synaptic plasticity processes. The splice isoform np65
      associates with synapses in an activity-dependent manner and has been shown to
      play a role for the induction of hippocampal long-term potentiation in rodents.
      We have therefore analyzed the distribution of neuroplastins in human brain.
      Neuroplastin is present in many neuronal cell types of the forebrain and
      cerebellum and immunoreactive label covers the cell soma, neurites and also
      puncta in the neuropil were visible. Interestingly, we found some remarkable
      species differences in the expression patterns of neuroplastins between the human
      and the rodent brain. In human brain np65 is prominently present in cerebellum
      while np55 is the predominant isoform in mouse and rat cerebellum. Moreover, the
      parasagittal stripe-type of staining seen with np55 in mouse cerebellum is not
      found in human brain. In addition we found no segregation of np65 immunolabel in
      hippocampal subregions like it was reported previously for the rat. These results
      might indicate different cellular functions of the molecule in different species.

PMID- 17196183
TI  - Gastric preloads of corn oil and mineral oil produce different patterns of
      increases of c-Fos-like immunoreacitve cells in the brain of 9-12 day-old rats.
AB  - Equivolumetric gastric preloads of corn oil and mineral oil administered to rats
      on postnatal day 12 (P12) inhibited intake equally during a 30-min test of
      independent ingestion (II), but preloads of corn oil inhibited intake
      significantly more than preloads of mineral oil on P15 and P18 [Weller, A.,
      Gispan, I.H., Armony-Sivan, R., Ritter, R.C., Smith, G.P., 1997. Preloads of corn
      oil inhibit independent ingestion on postnatal day 15 in rats. Physiol. Behav.
      62, 871-874]. It is possible that the equivalent inhibition of intake by the oil
      preloads on P12 resulted from the failure of the preabsorptive sensory properties
      of the preloads to be discriminated by peripheral or central sensory mechanisms.
      To investigate this possibility, we administered equivolumetric gastric preloads
      of 25% corn oil and 25% mineral oil to pups on P9-12 and counted the number of c
      Fos-like immunoreactive (CFLI) cells in central sites that are activated by food
      intake and postingestive preabsortive mechanisms in adult rats and in pups on P10
      11. The major result was that preloads of 25% corn oil and 25% mineral oil that
      produced equivalent inhibition of II intake produced differential increases of
      CFLI cells in the forebrain and hindbrain. Specifically, preloads of corn oil
      increased the number of CFLI cells in the caudal Nucleus Tractus Solitarius
      significantly more than preloads of mineral oil. Furthermore, preloads of corn
      oil increased the number of CFLI cells in the Paraventricular and Supraoptic
      nuclei, but preloads of mineral oil did not. This differential pattern of
      increases of CFLI cells is evidence that the brain discriminates the
      preabsorptive sensory properties of preloads of corn oil and mineral oil on P9
      12.

PMID- 17196185
TI  - Lack of the PAC1 receptor alters the circadian expression of VIP mRNA in the
      suprachiasmatic nucleus of mice.
AB  - PACAP in the retinohypothalamic tract mediates photic information to the
      suprachiasmatic nucleus via the PAC1 receptor. The diurnal and circadian VIP mRNA
      expressions in the suprachiasmatic nucleus of PAC1-/- and wild type mice were
      quantified. During light/dark cycles identical VIP mRNA rhythms were found while
      the oscillation pattern differed between the two types of animals during constant
      darkness. The results show that the circadian VIP mRNA expression is influenced
      by the absence of PAC1 signalling.

PMID- 17196184
TI  - Expression of drug transporters at the blood-brain barrier using an optimized
      isolated rat brain microvessel strategy.
AB  - Quantitative RT-PCR (qRT-PCR) and Western blotting studies on transporters at the
      blood-brain barrier (BBB) of isolated brain microvessels have produced
      conflicting data on their cellular distribution. A major problem is identifying
      cells expressing the genes of interest, since isolated brain microvessels are
      composed of several cell types and may be contaminated with mRNA or proteins from
      astrocytes and neurons. We isolated rat brain microvessels and examined
      microscopically samples at each step of isolation to evaluate microvessel purity.
      The expression of specific markers of endothelial cells (Glut-1, Flk-1),
      pericytes (Ng2), neurons (synaptophysin, Syn) and astrocytes (Gfap) was measured
      by qRT-PCR in order to select the protocol giving the least astrocyte and neuron
      mRNAs and the most endothelial mRNAs. We also evaluated the gene expression of
      drug transporters (Mdr1a, Mdr1b, Mrp1-5, Bcrp and Oatp-2) at each step to
      optimize their location in cells at the BBB. The Mdr1a, Mrp4, Bcrp and Oatp-2
      gene profiles were similar to those of endothelium markers. The profiles of Mrp2
      and Mrp3 closely resembled that of Ng2. Mrp5 and Mrp1 expression was not
      increased in the microvessel-enriched fraction, suggesting that they are
      ubiquitously expressed throughout the cortex parenchyma. We also evaluated by
      Western blotting the expression of P-gp, Mrp2, Gfap and Syn in the cortex and in
      the purest obtained microvessel fraction. Our results showed that P-gp expression
      strongly increased in microvessels whereas Mrp2 was not detected in any of the
      fraction. Surprisingly, Gfap expression increased in isolated microvessels
      whereas Syn was not detected. Our results showed that the strategy consisting of
      identifying gene expression at different steps of the protocol is useful to
      identify cells containing mRNA at the BBB and give overall similar results with
      protein expression.

PMID- 17196187
TI  - Rnd family genes are differentially regulated by 3,4
      methylenedioxymethamphetamine and cocaine acute treatment in mice brain.
AB  - Drugs of abuse induce alterations in cytoskeletal and cytoskeleton associated
      genes in several brain areas. We have previously shown that acute MDMA regulates
      the mRNA level of Rnd3, a Rho GTPase involved in actin cytoskeleton regulation,
      in mice striatum. In this study we investigated the effects of single
      administration of cocaine, another psychostimulant with a slightly different
      mechanism of action, on the mRNA levels of the three members of the Rnd genes
      family (Rnd1, Rnd2 and Rnd3). Mice were treated with either MDMA (9 mg/kg) or
      cocaine (20 mg/jg) and brain samples (i.e. hippocampus, striatum and prefrontal
      cortex) were processed for quantitative real-time PCR assay 1, 2, 4 and 6 h after
      the injections. The expression level of Rnd2 was differentially affected
      depending on the drug, brain area and time point after injection. Interestingly
      the two drugs up-regulate Rnd3 gene expression in the three structures tested
      with some differences in the timing. The effects of MDMA on Rnd3 appear earlier
      in the hippocampus as compared to cocaine, while it is the opposite in the
      prefrontal cortex. However, in the dorsal striatum, the two drugs induce an early
      and significant up-regulation of Rnd3 expression that is longer-lasting in the
      case of MDMA. In the case of cocaine contrarily to what was observed with MDMA,
      this modulation could not be blocked with the ERK activation inhibitor SL327
      suggesting that the two drugs lead to the same effect on Rnd3 by two distinct
      pathways.

PMID- 17196188
TI  - Premorbid exercising in specific cognitive tasks prevents impairment of
      performance in parkinsonian monkeys.
AB  - Adult Cebus apella monkeys were exposed to either one, two or four series of
      cognitive tasks that place a demand on working memory and inhibitory control
      (Spatial Delayed Response and Object Retrieval Detour), before administration of
      the neurotoxin 1-methyl-1-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Following
      MPTP treatment, monkeys receiving more than one series successfully reached
      criteria at delays similar to those attained during the pre-MPTP stage for the
      Spatial Delayed Response task and avoided increased perseveration in the Object
      Retrieval Detour task. Results provide evidence that protection towards a
      neurotoxin in specific cognitive performances can be increased by repeated
      exposure to task-specific cognitive demands and that motor and cognitive
      impairment following MPTP treatment can be effectively dissociated in primates.

PMID- 17196189
TI  - Ontogenesis of morphine-induced behavior in the cat.
AB  - We analyzed the behavioral responses to a single dose of morphine in kittens at
      postnatal (P) ages 7, 15, 30, 60, 90, and 120 days. Each kitten received 0.5 or
      3.0 mg/kg i.p. of morphine sulphate or saline vehicle. An average of 6.5 kittens
      were studied at each dose and age. An ethogram was constructed, based on morphine
      effects in adult cats, to score appropriate behaviors from direct observation and
      video sampling. After injection behaviors were sampled for periods of 2 min every
      15-30 min for a total of 4 h. The frequency of each selected behavior was scored
      at 2 s intervals during each of the 2 min periods and it was expressed as a
      percent of all time samples scored for the 4 h period. Statistical comparisons
      were made with control (saline) littermates. At P7-15 the drug's main effect was
      behavioral depression; i.e., kittens, away from the litter, laid sprawled as if
      with no muscle tonus; Nursing was suppressed and Vocalization was distressed.
      Mainly with the higher dose, at P30, morphine-specific behaviors appeared for the
      first time. With the kitten in a Sitting position, these included stereotypical
      Head and Paw Movements and body Torsion. At P60 other drug-elicited behaviors
      emerged, including Spinning, Retching, and Vomiting. By P90-120 the frequency of
      Head (16.0%) and Paw (16.9%) Movements doubled relative to P30-60. Morphine
      significantly changed frequencies of newly matured behaviors (in control kittens)
      including Sniffing and Licking (increased), and Grooming (decreased/blocked).
      Retching and Vomiting increased to adult levels. Morphine-induced hyperthermia
      was first detected at P60 and peaked by P90-P120. The early behavioral depression
      shifted to a pattern of increasing activity starting at P30 and peaking at P90
      120, at which time Sleep was absent and Laying was reduced, while Walking and
      Sitting were increased. We concluded that the maturation of the stereotypical
      behavioral responses to morphine in cats begins at about P30 and is completed
      between P90 and 120. Results are discussed in terms of developmental parameters
      and putative brain sites of morphine's actions.

PMID- 17196186
TI  - Effects of ex vivo transduction of mesencephalic reaggregates with bcl-2 on
      grafted dopamine neuron survival.
AB  - Survival rates of dopamine (DA) neurons grafted to the denervated striatum are
      extremely poor (5-20%). Gene transfer of survival promoting factors, such as the
      anti-apoptotic protein bcl-2, to mesencephalic DA neurons prior to
      transplantation (ex vivo transduction) offers a novel approach to increase graft
      survival. However, specific criteria to assess the efficacy of various vectors
      must be adhered to in order to reasonably predict successful gene transfer with
      appropriate timing and levels of protein expression. Cell culture results
      utilizing three different herpes simplex virus (HSV) vectors to deliver the
      reporter beta-galactosidase gene (lacZ) indicate that transduction of
      mesencephalic cells with a helper virus-free HSV amplicon (HF HSV-TH9lac) that
      harbors the 9-kb tyrosine hydroxylase (TH) promoter to drive lacZ gene expression
      elicits the transduction of the highest percentage (approximately 50%) of TH
      immunoreactive (THir) neurons without significant cytotoxic effects. This
      transduction efficiency and limited cytotoxicity was superior to that observed
      following transduction with helper virus-containing HSV (HC HSVlac) and helper
      virus-free HSV amplicons (HF HSVlac) expressing lacZ under the transcriptional
      control of the HSV immediate-early 4/5 gene promoter. Subsequently, we assessed
      the ability of HSV-TH9lac and the bcl-2 expressing HSV-TH9bcl-2 amplicon to
      transduce mesencephalic reaggregates. Although an increase in bcl-2 and beta
      galactosidase protein was induced by transduction, amplicon-mediated
      overexpression of bcl-2 did not lead to an increase in grafted THir neuron
      number. Even with highly efficient viral vector-mediated transduction, our
      results demonstrate that ex vivo gene transfer of bcl-2 to mesencephalic
      reaggregates is ineffective in increasing grafted DA neuron survival.

PMID- 17196190
TI  - The sound of motion in spoken language: visual information conveyed by acoustic
      properties of speech.
AB  - Language is generally viewed as conveying information through symbols whose form
      is arbitrarily related to their meaning. This arbitrary relation is often assumed
      to also characterize the mental representations underlying language
      comprehension. We explore the idea that visuo-spatial information can be
      analogically conveyed through acoustic properties of speech and that such
      information is integrated into an analog perceptual representation as a natural
      part of comprehension. Listeners heard sentences describing objects, spoken at
      varying speaking rates. After each sentence, participants saw a picture of an
      object and judged whether it had been mentioned in the sentence. Participants
      were faster to recognize the object when motion implied by speaking rate matched
      the motion implied by the picture. Results suggest that visuo-spatial referential
      information can be analogically conveyed and represented.

PMID- 17196191
TI  - Modulating biochemical perturbations during 72-hour machine perfusion of kidneys:
      role of preservation solution.
AB  - This study documents renal biochemistry during hypothermic machine perfusion of
      kidneys. It is intended to demonstrate that a comprehensive evaluation of organ
      viability during ex-vivo preservation is needed to increase the number of organs
      available for transplantation and to reduce the current renal discard rate.
      Porcine kidneys were hypothermically machine perfused for 72 h with either Unisol
      UHK or Belzer-Machine Perfusion Solution, (Belzer-MPS). Renal perfusate samples
      were periodically collected and biochemically analyzed. Significant differences
      were measured in the renal metabolic activity between the two experimental groups
      while similar values for traditional parameters such as renal flow rate and
      vascular resistance values were recorded. The effluent of UHK perfused kidneys
      showed strong metabolites and NH(4)(+) dynamics (P<0.05 vs. baseline), while the
      Belzer-MPS kidneys metabolic activity led to little or no change of the effluent
      biochemistry relative to baseline.

PMID- 17196192
TI  - Rescue of odontogenesis in Dmp1-deficient mice by targeted re-expression of DMP1
      reveals roles for DMP1 in early odontogenesis and dentin apposition in vivo.
AB  - Dentin matrix protein 1 (DMP1) is expressed in both pulp and odontoblast cells
      and deletion of the Dmp1 gene leads to defects in odontogenesis and
      mineralization. The goals of this study were to examine how DMP1 controls dentin
      mineralization and odontogenesis in vivo. Fluorochrome labeling of dentin in Dmp1
      null mice showed a diffuse labeling pattern with a 3-fold reduction in dentin
      appositional rate compared to controls. Deletion of DMP1 was also associated with
      abnormalities in the dentinal tubule system and delayed formation of the third
      molar. Unlike the mineralization defect in Vitamin D receptor-null mice, the
      mineralization defect in Dmp1-null mice was not rescued by a high calcium and
      phosphate diet, suggesting a different effect of DMP1 on mineralization. Re
      expression of Dmp1 in early and late odontoblasts under control of the Col1a1
      promoter rescued the defects in mineralization as well as the defects in the
      dentinal tubules and third molar development. In contrast, re-expression of Dmp1
      in mature odontoblasts, using the Dspp promoter, produced only a partial rescue
      of the mineralization defects. These data suggest that DMP1 is a key regulator of
      odontoblast differentiation, formation of the dentin tubular system and
      mineralization and its expression is required in both early and late odontoblasts
      for normal odontogenesis to proceed.

PMID- 17196194
TI  - Self-administration of cocaine-antihistamine combinations: super-additive
      reinforcing effects.
AB  - Histamine H1 receptor antagonists have some behavioral effects that predict abuse
      liability. In the present study, diphenhydramine and cocaine each maintained i.v.
      self-administration under a progressive-ratio schedule in rhesus monkeys. When
      cocaine and DPH were combined in a 1:1 ratio of the ED50s, the combination was
      super-additive in all monkeys. The data predict that the combination of cocaine
      and histamine H1 receptor antagonists would have enhanced potential for abuse
      relative to either drug alone.

PMID- 17196193
TI  - FGF10 signaling controls stomach morphogenesis.
AB  - Maintenance of progenitor cell properties in development is required for proper
      organogenesis of most organs, including those derived from the endoderm. FGF10
      has been shown to play a role in both lung and pancreatic development. Here we
      find that FGF10 signaling controls stomach progenitor maintenance, morphogenesis
      and cellular differentiation. Through a characterization of the initiation of
      terminal differentiation of the three major gastric regions in the mouse,
      forestomach, corpus and antrum, we first describe the existence of a "secondary
      transition" event occurring in mouse stomach between E15.5 and E16.5. This
      includes the formation of terminally differentiated squamous cells, parietal,
      chief and gastric endocrine cells from a pre-patterned gastric progenitor
      epithelium. Expression analysis of both FGF and Notch signaling components
      suggested a role of these networks in such progenitors, which was tested through
      ectopically expressing FGF10 in the developing posterior stomach. These data
      provide evidence that gastric gland specification and progenitor cell maintenance
      is controlled by FGF10. The glandular proliferative niche was disrupted in pPDX
      FGF10(FLAG) mice leading to aberrant gland formation, and endocrine and parietal
      cell differentiation was attenuated. These effects were paralleled by changes in
      Hes1, Shh and Wnt6 expression, suggesting that FGF10 acts in concert with
      multiple morphogenetic signaling systems during gastric development.

PMID- 17196196
TI  - Dynamic distribution of Spatial during mouse spermatogenesis and its interaction
      with the kinesin KIF17b.
AB  - The Spatial gene is expressed in highly polarized cell types, such as epithelial
      cells in the thymus, neurons in the brain and germ cells in the testis. In this
      study, we report the characterization and distribution of Spatial proteins during
      mouse spermatogenesis. Besides Spatial-epsilon and -delta, we show that the newly
      described short isoform Spatial-beta is expressed specifically in round
      spermatids. Using indirect immunofluorescence, we detected Spatial in the cytosol
      of the early round spermatid. By the end stages of round spermatids, Spatial is
      concentrated at the opposite face of the acrosome near the nascent flagellum and
      in the manchette during the elongation process. Finally in mature sperm, Spatial
      persists in the principal piece of the tail. Moreover, we found that Spatial
      colocalizes with KIF17b, a testis-specific isoform of the brain kinesin-2 motor
      KIF17. This colocalization is restricted to the manchette and the principal piece
      of the sperm tail. Further, coimmunoprecipitation experiments of native proteins
      from testis lysates confirmed Spatial-KIF17b association through the long Spatial
      epsilon isoform. Together, these findings imply a function of Spatial in
      spermatid differentiation as a new cargo of kinesin KIF17b, in a microtubule
      dependent mechanism specific to the manchette and the principal piece of the
      sperm tail.

PMID- 17196197
TI  - Hormonal regulation of the steroidogenic acute regulatory protein (StAR) in
      gonadal tissues of the Atlantic croaker (Micropogonias undulatus).
AB  - The steroidogenic acute regulatory protein (StAR), a member of the StAR-related
      lipid transfer domain (START) family, is critical to regulated steroidogenesis in
      vertebrates. We have isolated a cDNA encoding StAR from a well-studied model of
      teleost physiology, the Atlantic croaker Micropogonias undulatus. This cDNA (1204
      nucleotides total length) contains an open reading frame of 858 nucleotides
      encoding a protein of 286 amino acids. Molecular phylogenetic analysis indicates
      the putative Atlantic croaker StAR protein is more closely related to StAR
      proteins (62-85% identity) than to the related START protein MLN-64 (28-31%
      identity). Green monkey kidney cells (COS-1) cotransfected with Atlantic croaker
      StAR and human cholesterol side chain cleavage (SCC) expression constructs are
      able to produce significantly more pregnenolone than cells transfected with SCC
      alone. StAR mRNA is detected in the Atlantic croaker head kidney by reverse
      transcriptase-polymerase chain reaction (RT-PCR) and in the kidney and
      hypothalamus in some individuals. Gonadal StAR gene expression is below the level
      of detection by RT-PCR in most individuals, but can be detected using fluorescent
      probes in quantitative RT-PCR. StAR mRNA is not detected in the Atlantic croaker
      brain. Six hour in vitro treatment of Atlantic croaker ovarian follicles with
      human chorionic gonadotropin (hCG) is insufficient to significantly alter StAR
      mRNA levels; however, 24 h hCG treatment induces StAR mRNA levels 17-fold over
      untreated controls. Neither 6 nor 24 h treatment with hCG significantly alters
      StAR mRNA levels in Atlantic croaker testicular minces. Likewise, 6h in vitro
      treatment with estradiol, testosterone or the maturation-inducing steroid
      17,20beta,21-trihydroxy-4-pregnen-3-one is without effect on gonadal StAR mRNA
      levels.

PMID- 17196195
TI  - Mapping of an origin of DNA replication in the promoter of fragile X gene FMR1.
AB  - An origin of bidirectional DNA replication was mapped to the promoter of the FMR1
      gene in human chromosome Xq27.3, which has been linked to the fragile X syndrome.
      This origin is adjacent to a CpG island and overlaps the site of expansion of the
      triplet repeat (CGG) at the fragile X instability site, FRAXA. The promoter
      region of FMR2 in the FRAXE site (approximately 600 kb away, in chromosome band
      Xq28) also includes an origin of replication, as previously described [Chastain
      II, P.D., Cohen, S.M., Brylawski, B.P., Cordeiro-Stone, M., Kaufman, D.G., 2006.
      A late origin of DNA replication in the trinucleotide repeat region of the human
      FMR2 gene. Cell Cycle 5, 869-872]. FMR1 transcripts were detected in foreskin and
      male fetal lung fibroblasts, while FMR2 transcripts were not. However, both FMR1
      and FMR2 were found to replicate late in S phase (approximately 6 h into the S
      phase of normal human fibroblasts). The position of the origin of replication
      relative to the CGG repeat, and perhaps the late replication of these genes,
      might be important factors in the susceptibility to triplet repeat amplification
      at the FRAXA and FRAXE sites.

PMID- 17196198
TI  - Role of insulin, insulin-like growth factors, and muscle regulatory factors in
      the compensatory growth of the trout (Oncorhynchus mykiss).
AB  - To examine the various mechanisms involved in compensatory growth in Oncorhynchus
      mykiss, an experimental protocol involving 1, 2 or 4 weeks of fasting followed by
      a single ad libitum re-feeding period of 4 weeks was designed for alevins.
      Morphological parameters including body weight, specific growth rates (SGR), and
      coefficient factor decreased significantly during fasting. Re-feeding accelerated
      growth and restored final body weight in groups previously fasted. Plasma insulin
      and glucose decreased in fasting, while normal levels were restored in all re-fed
      groups. The expression profile of insulin-like growth factors (IGFs) in liver and
      of the main muscle growth regulators in white muscle was examined using real-time
      quantitative RT-PCR. Fasting decreased the expression of IGF-I mRNA in both
      tissues, while re-feeding restored expression to control values. In contrast, IGF
      II expression was not affected by any treatment in either tissue. Insulin- and
      IGF-I-binding assays in partial semi-purifications (of soluble proteins) in white
      skeletal muscle showed that insulin binding was not affected by either fasting or
      re-feeding, whereas fasting up-regulated IGF-I binding. The expression of IGFRIb
      mRNA in white skeletal muscle also increased with fasting, while IGFRIa increased
      with re-feeding, indicating that the two receptor isoforms are differentially
      regulated. The mRNA expression of myogenic regulator factors and fibroblast
      growth factors (FGFs) was not affected throughout the experiment, except for
      myogenin, which first decreased and then showed a rebound effect after 4 weeks of
      fasting. Myostatin mRNA expression did not change during fasting, although re
      feeding caused a significant decrease. In conclusion, re-feeding of previously
      fasted trout induced compensatory growth. The differential regulation in muscle
      expression of IGF-I, IGF-I receptors, and myostatin indicates their contribution
      to this compensatory mechanism.

PMID- 17196199
TI  - Effects of larval-juvenile treatment with perchlorate and co-treatment with
      thyroxine on zebrafish sex ratios.
AB  - The objective of this study was to determine the effect of larval-juvenile
      exposure to perchlorate, a thyroid hormone synthesis inhibitor, on the
      establishment of gonadal sex ratios in zebrafish. Zebrafish were exposed to
      untreated water or water containing perchlorate at 100 or 250 ppm for a period of
      30 days starting at 3 days postfertilization (dpf). Recovery treatments consisted
      of a combination of perchlorate and exogenous thyroxine (T4; 10 nM). Thyroid
      histology was assessed at the end of the treatment period (33 dpf), and gonadal
      histology and sex ratios were determined in fish that were allowed an additional
      10-day period of growth in untreated water. As expected, exposure to perchlorate
      caused changes in thyroid histology consistent with hypothyroidism and these
      effects were reversed by co-treatment with exogenous T4. Perchlorate did not
      affect fish survival but co-treatment with T4 induced higher mortality. However,
      relative to the corresponding perchlorate concentration, co-treatment with T4
      caused increased mortality only at a perchlorate concentration of 100 ppm.
      Perchlorate alone or in the presence of T4 suppressed body length at 43 dpf
      relative to control values. Perchlorate exposure skewed the sex ratio toward
      female in a concentration-dependent manner, and co-treatment with T4 not only
      blocked the feminizing effect of perchlorate but also overcompensated by skewing
      the sex ratio towards male. Moreover, co-treatment with T4 advanced the onset of
      spermatogenesis in males. There was no clear association between sex ratios and
      larval survival or growth. We conclude that endogenous thyroid hormone plays a
      role in the establishment of gonadal sex phenotype during early development in
      zebrafish.

PMID- 17196201
TI  - Delayed behavioral effects of postnatal exposure to corticosterone in the zebra
      finch (Taeniopygia guttata).
AB  - Early developmental conditions can significantly influence the growth and
      survival of many animal species. We studied the consequences of exposure to
      corticosterone (CORT), a stress hormone, during the nestling stage on two
      behavioral traits (neophobia, social dominance) measured when the birds had
      reached independence. Nestling zebra finches (Taeniopygia guttata) were exposed
      twice daily to exogenous CORT via oral administration for a 12-day period up
      until fledging. Experimental CORT administration depressed nestling growth rates,
      confirming results previously obtained in this species. Our data on neophobic
      behavior revealed a significant interaction between sex and treatment, with CORT
      dosed males showing reduced latencies to approach a novel object, while there was
      little effect of corticosterone treatment on female neophobia. There was no
      significant effect of age (30 or 50 days), however, there was a non-significant
      trend towards an interaction between treatment and age, with neophobia increasing
      with age in the CORT-dosed birds, but decreasing in controls. At 50 days of age
      previous exposure to corticosterone resulted in reduced success in competitions
      for a non-food-based resource (a perch) in both sexes. There were no effects of
      brood size on any behavioral traits measured here, but this may be due to the
      small range in brood size used. Our results show that elevated levels of stress
      hormones during postnatal development can have significant effects on important
      behavioral traits, i.e., neophobia and dominance. Moreover, they confirm the
      importance of rearing conditions in shaping adult phenotypes.

PMID- 17196200
TI  - Individualities in a flock of free-roaming greylag geese: behavioral and
      physiological consistency over time and across situations.
AB  - The concept of personality implies individual differences in behavior and
      physiology that show some degree of repeatability/consistency over time and
      across contexts. Most studies of animal personality, particularly studies of
      individuals' variation in physiological mechanisms, have been conducted on
      selected individuals in controlled conditions. We attempted to detect consistent
      behaviors as well as physiological patterns in greylag ganders (Anser anser) from
      a free-roaming flock living in semi-natural conditions. We tested 10 individuals
      repeatedly, in a handling trial, resembling tests for characterization of
      "temperaments" in captive animals. We recorded the behavior of the same 10
      individuals during four situations in the socially intact flock: (1) a "low
      density feeding condition", (2) a "high density feeding condition", (3) a "low
      density post-feeding situation" and (4) while the geese rested. We collected
      fecal samples for determination of excreted immuno-reactive corticosterone (BM)
      and testosterone metabolites (TM) after handling trials, as well as the "low
      density feeding" and the "high density feeding" conditions. BM levels were very
      highly consistent over the repeats of handling trials, and the "low density
      feeding condition" and tended to be consistent over the first two repeats of the
      "high density feeding condition". Also, BM responses tended to be consistent
      across contexts. Despite seasonal variation, there tended to be inter-test
      consistency of TM, which pointed to some individual differences in TM as well.
      Aggressiveness turned out to be a highly repeatable trait, which was consistent
      across social situations, and tended to correlate with an individual's resistance
      during handling trials. Also, "proximity to the female partner" and "sociability"
      - the average number of neighboring geese in a close distance while resting -
      were consistent. We conclude that aggressiveness, "affiliative tendencies" and
      levels of excreted corticosterone and testosterone metabolites may be crucial
      factors of personality in geese.

PMID- 17196202
TI  - Pregnancy outcome for HIV-1-infected women with Streptococcus agalactiae.

PMID- 17196203
TI  - Recurrent pregnancy loss and obstetric outcome.

PMID- 17196204
TI  - Concomitant pelvic reconstructive surgery and transobturator tape for stress
      urinary incontinence.

PMID- 17196205
TI  - Mid-trimester dilation and evacuation with laminaria does not increase the risk
      for severe subsequent pregnancy complications.
AB  - OBJECTIVE: To evaluate subsequent pregnancy outcomes in women with a previous mid
      trimester (12-24 weeks) pregnancy termination by dilation and evacuation (D&E) as
      compared to women without a previous D&E. METHOD: Medical records for women who
      underwent a D&E between 1995 and 2003 were identified and reviewed. Women with
      subsequent pregnancies were compared on a 1:2 basis with women in a control group
      who had viable pregnancies and no previous mid-trimester DE. Outcomes of interest
      included preterm labor, placental abnormalities, and a composite complication
      outcome. RESULTS: Of the 317 women who underwent a D&E, 85 had viable subsequent
      pregnancies. These women delivered slightly earlier than the 170 controls (38.9
      versus 39.5 weeks, p=0.001), although there was no statistically significant
      difference between the two groups with regard to birth weights, spontaneous
      preterm delivery, abnormal placentation, and overall complication rate.
      CONCLUSIONS: Mid-trimester termination by D&E does not increase the rate of
      clinically significant subsequent pregnancy complications.

PMID- 17196206
TI  - Dyslipidemia shifts the tissue factor/tissue factor pathway inhibitor balance
      toward increased thrombogenicity in atherosclerotic plaques: evidence for a
      corrective effect of statins.
AB  - BACKGROUND: Tissue factor (TF) is a key mediator of atherosclerotic plaque
      thrombogenicity and may be regulated by plaque TF pathway inhibitor (TFPI). High
      atherogenic lipoproteins are a well-known arterial risk factor, but their effects
      on the TF/TFPI balance in atherosclerotic plaques, as well as those of widely
      used lipid-lowering agents such as statins, are incompletely understood.
      OBJECTIVES: We analyzed the TF/TFPI balance in carotid plaques from 86 patients,
      according to the presence of dyslipidemia and statin therapy. RESULTS: In
      patients with untreated dyslipidemia (ApoB/ApoA1 ratio >0.7) (D+) (n=44), TF
      antigen (TF) tended to be higher than in those without dyslipidemia (D-) (n=16).
      In patients with statins (S+) (n=26), TF was lower than in D+ (p=0.02) and
      similar to that of D- patients. TFPI antigen was higher in D- than in D+ and S+
      patients (p<or=0.02). As a result, the TF/TFPI (mol/mol) ratio was higher in D+
      than in D- or S+ patients (p<or=0.005). TF activity correlated to TF/TFPI ratio
      (p<0.0001), and was higher in the D+ than in the D- and in the S+ patients
      (p=0.02). Among analyzed clinical risk factors and biological parameters,
      including CRP, dyslipidemia was the only independent predictor for low plaque
      TFPI and high TF/TFPI ratio. Histochemistry showed that TF and TFPI were mainly
      expressed in macrophage-rich regions surrounding the lipid-rich core in the three
      groups. CONCLUSIONS: These results indicate that dyslipidemia is associated with
      a shift of the TF/TFPI balance and of TF activity toward higher plaque thrombotic
      potential. Statins correct this equilibrium mainly by decreasing plaque TF
      together with blood atherogenic lipoproteins.

PMID- 17196207
TI  - Effects of cholesterol ester transfer protein (CETP) gene on adiposity in
      response to long-term overfeeding.
AB  - Cholesterol ester transfer protein (CETP) plays a key role in remodeling
      triglyceride-rich particles and high-density lipoproteins (HDL). We investigated
      CETP sequence variants in response to long-term overfeeding (100 days) in 12
      pairs of male monozygotic twins (mean age+/-S.D.: 21+/-2 years). Body fat mass
      (FM), abdominal subcutaneous (ASF) and visceral fat (AVF), and plasma
      lipoproteins were determined. The CETP variants C>T/In9 (rs289714) and G>A/Ex14
      (rs5882, or I405V) were investigated by RFLP-PCR methodologies. Before
      overfeeding, the CETP CC/In9 (n=18) genotype was associated with lower FM
      compared to the C>T/In9 heterozygotes. Overfeeding induced more FM and ASF
      accretion in C>T/In9 carriers (P<or=0.05). CETP V405V homozygotes (n=8) had lower
      BMI, FM, and ASF before overfeeding than those with the I405I (n=6) or I405V
      (n=10) genotypes. However, V405V subjects had the largest gain in AVF with
      overfeeding (P=0.02). Decreases from baseline were significantly different across
      the I405V genotypes for HDL-C, HDL-Apo AI, HDL(2), and HDL(3) (P<or=0.05). Our
      data suggests that CETP sequence variation contributes to the undesirable changes
      in adiposity and HDL-C levels when exposed to excessive calorie consumption and
      may be potentially helpful to identify individuals with the metabolic syndrome
      who are at higher risk of cardiovascular disease.

PMID- 17196208
TI  - Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory activity
      in patients with coronary artery disease--a randomized placebo-controlled study.
AB  - The balance between different immunological stimuli is essential in the
      progression and stabilization of atherosclerotic plaques. Immune regulation has
      been suggested as potential target for the treatment of atherosclerotic disease.
      We sought to determine whether treatment with pentoxifylline, a phosphodiesterase
      inhibitor with immunomodulating properties, could reduce the pro-inflammatory
      response observed in patients with acute coronary syndromes (ACS) and increase
      anti-inflammatory activity. In a double-blind, prospective, placebo-controlled
      study, 64 patients with ACS were randomized to receive pentoxifylline 400mg TID
      or placebo for 6 months. Analysis of the pro-inflammatory markers, C-reactive
      protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis
      factor (TNF)-alpha and the anti-inflammatory cytokines, transforming growth
      factor (TGF)-beta1 and IL-10 were done at baseline, 1 and 6 months.
      Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF
      alpha compared to placebo after 6 months (P=0.04 and P<0.01, respectively). IL-12
      increase was significantly less pronounced with pentoxifylline (P=0.04). The
      levels of the anti-inflammatory cytokine, IL-10, also declined significantly less
      in the pentoxifylline group compared to placebo (P<0.01) with a trend towards a
      higher increase of TGF-beta1 in the former group (P=0.16). Pentoxifylline reduces
      pro-inflammatory and increases anti-inflammatory response in patients with ACS
      and may have beneficial clinical effects on cardiovascular events.

PMID- 17196209
TI  - Detection of familial hypercholesterolemia in a cohort of children with
      hypercholesterolemia: results of a family and DNA-based screening.
AB  - The diagnosis of familial hypercholesterolemia (FH) in unselected children is
      difficult due to the frequent overlap of cholesterol values in affected and non
      affected and the paucity of physical signs. Nevertheless, detection and treatment
      of FH in childhood has been advocated to prevent atherosclerosis in these
      patients. Here, we report the results of a screening program in a cohort of 157
      unrelated, hypercholesterolemic (HC) children (age range 2-15 years; mean 8.3+/
      3.4 years) carried out by a combination of family study and molecular analysis of
      the LDLR gene. On the basis of the familial phenotype, 27 (17.2%) were classified
      as probable FH and 49 (31.2%) as affected by FCHL. Among probable FH children, 14
      (51.8%) carried mutant LDLR alleles, giving an overall 8.9% prevalence of FH.
      Most of LDLR variants were already reported, but three new mutations G266C,
      T368M, and D451Y were identified. Beside increased TC and LDL-C (p<0.001), FH
      children showed decreased HDL-C (p<0.05) and higher prevalence of family history
      of CAD when compared to non-FH children. None presented tendon xanthomas. We
      estimated that LDL-C >3.9 mmol/L was the best cut off value for diagnosing FH in
      these children, showing 79% sensitivity and 71.0% specificity. We propose the use
      of a LDL-C cut off level associated with a family study to identify FH among HC
      children.

PMID- 17196210
TI  - Relative contribution of the pressure variations under the feet and body weight
      distribution over both legs in the control of upright stance.
AB  - The resultant centre of pressure (CP(Res)) trajectories are aimed at controlling
      body movements in upright stance. When standing on two legs, these trajectories
      are generated by exerting reaction forces under each foot and by loading
      unloading mechanisms intervening at the hip level. To assess the respective
      contribution of each of these factors in stance maintenance, a group of healthy
      individuals were tested in several conditions including standing quietly and
      voluntarily producing under each foot larger CP displacements in phase and in
      opposite phase along medio-lateral (ML) and antero-posterior (AP) axes. The
      results, based on the computation of coefficients of correlation between CP(Res)
      trajectories and various time series including the relative body weight applied
      to one leg and plantar CP trajectories, highlight some differences according to
      the axes along which the displacements take place and the amplitudes of the
      movements. Furthermore, the comparison of the CP(Res) trajectories resulting from
      each one of these two factors reveals the predominant role played by the loading
      unloading mechanisms intervening at the hip level for the movements along the ML
      axis and those of the plantar CP displacements along the AP axis. Increasing the
      plantar CP displacements in phase or in opposite phase substantially modifies
      these contributions although without inferring a shift to the benefit of the
      other mechanism. The specific morphology of the ankle and hip joints implicated
      in this postural task plainly explains this postural control organisation. In
      particular, the link between the segmental configuration of the lower limbs and
      these mechanisms are discussed.

PMID- 17196211
TI  - Parametric geometry exploration of the human carotid artery bifurcation.
AB  - A parametric computational model of the human carotid artery bifurcation is
      employed to demonstrate that it is only necessary to simulate approximately one
      half of a single heart pulse when performing a global exploration of the
      relationships between shear stress and changes in geometry. Using design of
      experiments and surface fitting techniques, a landscape is generated that
      graphically depicts these multi-dimensional relationships. Consequently, whilst
      finely resolved, grid and pulse independent results are traditionally demanded by
      the computational fluid dynamics (CFD) community, this strategy demonstrates that
      it is possible to efficiently detect the relative impact of different geometry
      parameters, and to identify good and bad regions of the landscape by only
      simulating a fraction of a single pulse. Also, whereas in the past comparisons
      have been made between the distributions of appropriate shear stress metrics,
      such as average wall shear stress and oscillatory shear index, this strategy
      requires a figure of merit to compare different geometries. Here, an area
      weighted integral of negative time-averaged shear stress, tau , is used as the
      principal objective function, although the discussion reveals that the extent as
      well as the intensity of reverse flow may be important. Five geometry parameters
      are considered: the sinus bulb width, the angles and the outflow diameters of the
      internal carotid artery (ICA) and external carotid artery (ECA). A survey of the
      landscape confirms that bulb shape has the dominant effect on tau with maximum
      tau occurring for large bulb widths. Also, it is shown that different sets of
      geometric parameters can produce low values of tau by either relatively small
      intense areas, or by larger areas of less intense reverse flow.

PMID- 17196212
TI  - Maximum running speed limitations on terrestrial mammals: a theoretical approach.
AB  - Here we study maximum running speed (MRS) limitations on a previously proposed
      model of energetic and muscle-tendon unit functions on running mammals. In the
      present work the MRS and some anatomical or physiological limitations are
      estimated for mammals with body mass between 1.5 and 300 kg. The MRS variations
      with body mass are discussed and compared with results of previous experimental
      and observational studies. The tendon strength seems to be the most relevant
      limitation, but leg extensor muscle mass and metabolic costs could be relevant
      also. The physiological maximum muscle speed seems to be less important in the
      body mass range studied here.

PMID- 17196213
TI  - Analysis of class 1 residual solvents in pharmaceuticals using headspace
      programmed temperature vaporization-fast gas chromatography-mass spectrometry.
AB  - A sensitive method is presented for the fast screening and determination of
      residual class 1 solvents (1,1-dichloroethene, 1,2-dichloroethane, 1,1,1
      trichloroethane, carbon tetrachloride and benzene) in pharmaceutical products.
      The applicability of a headspace (HS) autosampler in combination with GC equipped
      with a programmed temperature vaporizer (PTV) and a MS detector is explored.
      Different injection techniques were compared. The benefits of using solvent vent
      injection instead of split or splitless-hot injection for the measurement of
      volatile compounds are shown: better peak shapes, better signal-to-noise ratios,
      and hence better detection limits. The proposed method is extremely sensitive.
      The limits of detection ranged from 4.9 ppt (benzene) to 7.9 ppt (1,2
      dichloroethane) and precision (measured as the relative standard deviation) was
      equal to or lower than 12% in all cases. The method was applied to the
      determination of residual solvents in nine different pharmaceutical products. The
      analytical performance of the method shows that it is appropriate for the
      determination of residual class 1 solvents and has much lower detection limits
      than the concentration limits proposed by the International Conference on
      Harmonization (ICH) of Technical Requirements for the Registration of
      Pharmaceuticals for Human Use. The proposed method achieves a clear improvement
      in sensitivity with respect to conventional headspace methods due to the use of
      the PTV.

PMID- 17196214
TI  - Application of central composite design to the optimisation of aqueous two-phase
      extraction of human antibodies.
AB  - The partition of human antibodies in aqueous two-phase systems (ATPSs) of
      polyethylene glycol (PEG) and phosphate was systematically studied using first
      pure proteins systems and then an artificial mixture of proteins containing
      1mg/ml human immunoglobulin G (IgG), 10mg/ml serum albumin and 2mg/ml myoglobin.
      Preliminary results obtained using pure proteins systems indicated that the PEG
      molecular weight and concentration, the pH value and the salts concentration had
      a pronounced effect on the partitioning behaviour of all proteins. For high ionic
      strengths and pH values higher than the isoelectric point (pI) of the contaminant
      proteins, IgG could be selectively recovered on the top phase. According to these
      results, a face centred composite design was performed in order to optimise the
      purification of IgG from the mixture of proteins. The optimal conditions for the
      isolation of IgG were observed for high concentrations of NaCl and low
      concentrations of both phase forming components. The best purification was
      achieved using an ATPS containing 8% (w/w) PEG 3350, 10% (w/w) phosphate pH 6 and
      15% (w/w) NaCl. A recovery yield of 101+/-7%, a purity of 99+/-0% and a yield of
      native IgG of 97+/-4% were obtained. Back extraction studies of IgG to a new
      phosphate phase were performed and higher yields were obtained using 10%
      phosphate buffer at pH 6. The total extraction yield was 76% and the purity 100%.

PMID- 17196215
TI  - Use of experimental design in the optimization of stir bar sorptive extraction
      for the determination of polybrominated diphenyl ethers in environmental
      matrices.
AB  - Stir bar sorptive extraction and liquid desorption (LD) followed by large volume
      injection and capillary gas chromatography coupled to mass spectrometry (SBSE-LD
      LVI-GC-MS), had been applied for the determination of ultra-traces of eleven
      polybrominated diphenylethers (PBDEs), from tetra to nona congeners (BDE-47, BDE
      100, BDE-99, BDE-85, BDE-154, BDE-153, BDE-183, BDE-197, BDE-196, BDE-207 and BDE
      206), in environmental matrices. Instrumental calibration under the selected-ion
      monitoring (SIM) mode acquisition and parameters that could affect the SBSE-LD
      efficiency are fully discussed. A complete randomized factorial design was
      established for the first time to optimize the main experimental parameters that
      affecting the SBSE-LD efficiency, including decisive interactions, which provides
      a more realistic picture of the sampling process. The analysis of variance
      (ANOVA) was the statistical method used to analyze data. From the data obtained,
      it can be emphasized that experimental parameters such as extraction time (240
      min), agitation speed (1250 rpm), methanol content (40%) and desorption
      conditions (acetonitrile, 15 min), were the best analytical compromise for the
      simultaneous determination between tetra and nona congeners in aqueous media. A
      remarkable recovery (65.6-116.9%) and repeatability (<12.1%) were attained,
      whilst the experimental data allowed very good agreement with predict theoretical
      equilibrium described by the octanol-water partition coefficients (K(PDMS/W)
      approximately = K(O/W)), with the exception of nona congeners since slightly
      lower yields were measured. Furthermore, excellent linear dynamic ranges from
      0.01 to 14.0 microg/L (r2>0.9917) and low detection limits (0.3-203.4 ng/L) were
      also achieved for the eleven congeners studied. The proposed methodology was
      applied for the determination of ultra-trace levels of PBDEs in waste water,
      sediments and printed board circuit matrices by the standard addition approach,
      showing to be reliable, sensitive and having a low sample amount requirement in
      compliance with the international regulatory bodies.

PMID- 17196216
TI  - A regenerable ruthenium tetraammine nitrosyl complex immobilized on a modified
      silica gel surface: preparation and studies of nitric oxide release and nitrite
      to-NO conversion.
AB  - Silica gel bearing isonicotinamide groups was prepared by further modification of
      3-aminopropyl-functionalized silica by a reaction with isonicotinic acid and 1,3
      dicyclohexylcarbodiimide to yield 3-isonicotinamidepropyl-functionalized silica
      gel (ISNPS). This support was characterized by means of infrared spectroscopy,
      elemental analysis, and specific surface area. The ISNPS was used to immobilize
      the [Ru(NH(3))(4)SO(3)] moiety by reaction with trans-[Ru(NH(3))(4)(SO(2))Cl]Cl,
      yielding [Si(CH(2))(3)(isn)Ru(NH(3))(4)(SO(3))]. The related immobilized
      [Si(CH(2))(3)(isn)Ru(NH(3))(4)(L)](3+/2+) (L=SO(2), SO(2-)(4), OH(2), and NO)
      complexes were prepared and characterized by means of UV-vis and IR spectroscopy,
      as well as by cyclic voltammetry. Syntheses of the nitrosyl complex were
      performed by reaction of the immobilized ruthenium ammine
      [Si(CH(2))(3)(isn)Ru(NH(3))(4)(OH(2))](2+) with nitrite in acid or neutral (pH
      7.4) solution. The similar results obtained in both ways indicate that the aqua
      complex was able to convert nitrite into coordinated nitrosyl. The reactivity of
      [Si(CH(2))(3)(isn)Ru(NH(3))(4)(NO)](3+) was investigated in order to evaluate the
      nitric oxide (NO) release. It was found that, upon light irradiation or chemical
      reduction, the immobilized nitrosyl complex was able to release NO, generating
      the corresponding Ru(III) or Ru(II) aqua complexes, respectively. The NO material
      could be regenerated from these NO-depleted materials obtained photochemically or
      by reduction. Regeneration was done by reaction with nitrite in aqueous solution
      (pH 7.4). Reduction-regeneration cycles were performed up to three times with no
      significant leaching of the ruthenium complex.

PMID- 17196217
TI  - Site-specifically conjugated anti-HER2 Affibody molecules as one-step reagents
      for target expression analyses on cells and xenograft samples.
AB  - Affibody molecules are a class of small and robust affinity proteins that can be
      generated to interact with a variety of antigens, thus having the potential to
      provide useful tools for biotechnological research and diagnostic applications.
      In this study, we have investigated Affibody-based reagents interacting
      specifically with the tyrosine kinase receptor HER2. A head-to-tail dimeric
      construct was site-specifically conjugated with different fluorescent and
      enzymatic groups resulting in reagents that were used for detection and
      quantification. The amount of cell surface expressed HER2 on eleven (11) well
      characterized cell lines was quantified relative to each other by flow cytometry
      and shown to correlate well with results from parallel analyses of HER2 mRNA
      levels measured by real-time PCR. Further, immunofluorescence microscopy studies
      of the cell lines and immunohistochemical analyses of cryosections of HER2
      expressing SKOV-3 xenografts showed strong staining of the plasma membrane of
      tumor cells with little background staining. Full-length HER2 protein could also
      be efficiently recovered from a cell extract by an immunoprecipitation procedure,
      using an Affibody ligand-based resin. These novel non-IgG derived reagents could
      be used to detect and quantify HER2 expression. By adapting the methods for use
      with Affibody molecules binding to other cell surface receptors, it is
      anticipated that also these receptors can be detected and quantified in a similar
      manner.

PMID- 17196218
TI  - Mapping the ADF/cofilin binding site on monomeric actin by competitive cross
      linking and peptide array: evidence for a second binding site on monomeric actin.
AB  - The binding sites for actin depolymerising factor (ADF) and cofilin on G-actin
      have been mapped by competitive chemical cross-linking using deoxyribonuclease I
      (DNase I), gelsolin segment 1 (G1), thymosin beta4 (Tbeta4), and vitamin D
      binding protein (DbP). To reduce ADF/cofilin induced actin oligomerisation we
      used ADP-ribosylated actin. Both vitamin D-binding protein and thymosin beta4
      inhibit binding by ADF or cofilin, while cofilin or ADF and DNase I bind
      simultaneously. Competition was observed between ADF or cofilin and G1,
      supporting the hypothesis that cofilin preferentially binds in the cleft between
      sub-domains 1 and 3, similar to or overlapping the binding site of G1. Because
      the affinity of G1 is much higher than that of ADF or cofilin, even at a 20-fold
      excess of the latter, the complexes contained predominantly G1. Nevertheless,
      cross-linking studies using actin:G1 complexes and ADF or cofilin showed the
      presence of low concentrations of ternary complexes containing both ADF or
      cofilin and G1. Thus, even with monomeric actin, it is shown for the first time
      that binding sites for both G1 and ADF or cofilin can be occupied simultaneously,
      confirming the existence of two separate binding sites. Employing a peptide array
      with overlapping sequences of actin overlaid by cofilin, we have identified five
      sequence stretches of actin able to bind cofilin. These sequences are located
      within the regions of F-actin predicted to bind cofilin in the model derived from
      image reconstructions of electron microscopical images of cofilin-decorated
      filaments. Three of the peptides map to the cleft region between sub-domains 1
      and 3 of the upper actin along the two-start long-pitch helix, while the other
      two are in the DNase I loop corresponding to the site of the lower actin in the
      helix. In the absence of any crystal structures of ADF or cofilin in complex with
      actin, these studies provide further information about the binding sites on F
      actin for these important actin regulatory proteins.

PMID- 17196219
TI  - Acidic pH-induced conformational changes in amyloidogenic mutant transthyretin.
AB  - Several proteins, including transthyretin (TTR), can generate in tissues
      extracellular insoluble aggregates, in the form of fibrils, that are associated
      with pathological states known as amyloidoses. To date, more than 80 different
      TTR point mutations have been associated with hereditary amyloidosis in humans.
      In vitro, the formation of amyloid fibrils by human TTR is known to be triggered
      by acidic pH. We show here that, in vitro, the natural amyloidogenic I84S and the
      non-natural I84A TTR mutant forms exhibit a propensity to produce fibrils in an
      acidic medium significantly higher than that of wild-type TTR. The two mutant
      forms have been crystallized at both neutral and acidic pH. Their neutral pH
      crystal structures are very similar to that of wild-type TTR, consistent with
      previous evidence indicating that only minor structural changes are induced by
      amyloidogenic mutations. On the contrary, their crystal structures at moderately
      low pH (4.6) show significant conformational differences as compared to their
      neutral pH structures. Remarkably, such changes are not induced in wild-type TTR
      crystallized at low pH. The most relevant consist of the unwinding of the TTR
      short alpha-helix and of the change in conformation of the loop connecting the
      alpha-helix to beta-strand F. Only one monomer of the crystallographic dimer is
      affected, causing a disruption of the tetrameric symmetry. This asymmetry and a
      possible destabilization of the tetrameric quaternary structure of TTR may be
      responsible for the amyloidogenic potential of the two TTR mutant forms at low
      pH.

PMID- 17196220
TI  - Local encoding of computationally designed enzyme activity.
AB  - One aim of computational protein design is to introduce novel enzyme activity
      into proteins of known structure by predicting mutations that stabilize
      transition states. Previously, we showed that it is possible to introduce triose
      phosphate isomerase activity into the ribose-binding protein of Escherichia coli
      by constructing 17 mutations in the first two layers of residues that surround
      the wild-type ligand-binding site. Here, we report that these mutations can be
      "transplanted" into a homologous ribose-binding protein, isolated from the
      hyperthermophilic bacterium Thermoanaerobacter tengcongensis, with retention of
      catalytic activity, substrate affinity, and reaction pH dependence. The observed
      10(5)-10(6)-fold rate enhancement corresponds to 70% of the maximally known
      transition-state binding energy. The wild-type sequences in these two homologues
      are almost perfectly conserved in the vicinity of their ribose-binding sites, but
      diverge significantly at increasing distance from these sites. The results
      demonstrate that the computationally designed mutations are sufficient to encode
      the observed enzyme activity, that all the observed activity is encoded locally
      within the layer of residues directly in contact with the substrate and that, in
      this case, at least 70% of transition state stabilization energy can be achieved
      using straightforward considerations of stereochemical complementarity between
      enzyme and reactants.

PMID- 17196222
TI  - Alanine racemase from Helicobacter pylori NCTC 11637: purification,
      characterization and gene cloning.
AB  - The Helicobacter pylori NCTC 11637 alanine racemase gene, alr1, was cloned based
      on a putative alanine racemase gene, alr, of H. pylori 26695. The protein, Alr1,
      was purified to homogeneity from Escherichia coli MB2795 cells harboring the alr1
      gene. The protein exclusively catalyzes the conversion of l-alanine to the d
      isomer with K(m) and V(max) values of 100 mM and 909 mumol min(-1) mg(-1),
      respectively. The values are 16-fold higher than those for the reaction in the
      reverse direction. The molecular weight of Alr1 is 42,000 by SDS-PAGE, and 68,000
      by gel-filtration analysis. The optimal pH and temperature are pH 8.3 and 37
      degrees C, respectively, in good accordance with the characteristics shown by the
      alanine racemase purified from H. pylori NCTC 11637 cells. Pyridoxal 5'-phosphate
      was suggested to be the cofactor. The physiological function of Alr1 is discussed
      regarding energy production in the microbial cells.

PMID- 17196221
TI  - Mechanism of translation based on intersubunit complementarities of ribosomal
      RNAs and tRNAs.
AB  - A universal rule is found about nucleotide sequence complementarities between the
      regions 2653-2666 in the GTPase-binding site of 23S rRNA and 1064-1077 of 16S
      rRNA as well as between the region 1103-1107 of 16S rRNA and GUUCG (or GUUCA) of
      tRNAs. This rule holds for all species in the living kingdoms except for two
      protista mitochondrial rRNAs of Trypanosoma brucei and Plasmodium falciparum. We
      found that quite similar relationships for the two species hold under the
      assumption presented in the present paper. The complementarity between T-loop of
      tRNA and the region 1103-1107 of 16S rRNA suggests that the first interaction of
      a ribosome with aminoacyl-tRNAEF-TuGTP ternary complex or EF-GGDP complex could
      occur at the region 1103-1107 of 16S rRNA with the T-loop-D-loop contact region
      of the ternary complex or the domain IV-V bridge region of the EF-GGDP complex.
      The second interaction should occur between the A-site codon and the anticodon
      loop or between the anticodon stem/loop of A-site tRNA and the tip of domain IV
      of EF-G. The above stepwise interactions would facilitate the collision of the
      region 1064-1077 of 16S rRNA with the region around A2660 at the alpha
      sarcin/ricin loop of 23S rRNA. In this way, the universal rule is capable of
      explaining how spectinomycin-binding region of 16S rRNA takes part in
      translocation, how GTPases such as EF-Tu and EF-G can be introduced into their
      binding site on the large subunit ribosome in proper orientation efficiently and
      also how driving forces for tRNA movement are produced in translocation and codon
      recognition. The analysis of T-loops of all tRNAs also presents an evolutionary
      trend from a random and seemingly primitive sequence, as defined to be Y type, to
      the most developed structure, such as either 5G7 or 5A7 types in the present
      definition.

PMID- 17196223
TI  - Evaluation of the mussel Perna perna as a biomonitor of polycyclic aromatic
      hydrocarbon (PAH) exposure and effects.
AB  - The mussel Perna perna was used to monitor and assess areas suspected of oil
      contamination by transplanting animals from unimpacted to impacted sites and vice
      versa. The deployment lasted for three months during which total PAH were
      measured in seawater samples collected every 15 days. PAH concentrations were
      determined in mussel tissue monthly. The lysosomal neutral red assay and the
      condition index were used as biomarkers of the adverse biological effects. The
      PAH concentration in mussels at unimpacted sites, prior to deployment was ca. 100
      microg kg(-1) but increased to 300 microg kg(-1) after three months at the
      contaminated site. Mussels transplanted to the uncontaminated site showed a
      decrease from 380 to 80 microg kg(-1). Significant changes in lysosomal stability
      occurred within one month of the beginning of the transposition; in contrast
      condition indexes were not correlated with the observed changes in PAH
      concentration.

PMID- 17196224
TI  - Longchain n-3 polyunsaturated fatty acids and microvascular reactivity:
      observation in the hamster cheek pouch.
AB  - Previous experiments in our laboratory, using the hamster cheek pouch
      microcirculation, have shown that precapillary vessels exhibit spontaneous
      rhythmic luminal variations, termed vasomotion, a myogenic activity sustained by
      a balance between membrane currents among which polarizing K(+) currents play an
      important role. In these microvessels, endothelium-derived relaxing factors
      (EDRFs) seem to regulate arteriolar diameter [via nitric oxide (NO) and cyclic
      GMP] and vasomotion [probably via endothelium-derived hyperpolarizing factor
      (EDHF)]. Fish or fish oil diet can decrease the risk of cardiovascular diseases,
      probably by modifying the conductance of selective ion channels, such as K(+)
      and/or Ca(++), and/or increasing the production of vasodilators, such as NO. To
      investigate its effect on microvascular reactivity, using the same preparation
      and an intravital microscope coupled to a closed circuit TV system, male hamsters
      were treated for 14 days, twice a day, with 0.4 mL/100 g body weight with fish or
      olive oil. An attempt was also undertaken to record in arterioles, in vivo, the
      membrane potential of smooth muscle cells during their vasomotor activity
      combining conventional microelectrode and intravital microscopy techniques. The
      effects of topical application of two vasodilators, acetylcholine [endothelium
      dependent one, NO release and membrane hyperpolarization via Ca(++)-activated
      K(+) channels (K(Ca))] and sodium nitroprusside (endothelium-independent, NO
      donor and no change on membrane potential) and two vasoconstrictors which
      elicited membrane depolarization via Ca(++) channels, phenylephrine (alpha(1)
      adrenergic receptor agonist) and serotonin (5-hydroxi-tryptamine) on mean
      internal diameter of arterioles and venules, arteriolar blood flows, spontaneous
      arteriolar vasomotion frequency and amplitude and functional capillary density
      (FCD, number of capillaries with flowing red blood cells per unit area of tissue)
      were determined. Anesthesia was induced by sodium pentobarbital (i.p.) and
      maintained with alpha-chloralose through the femoral vein. In the presence of
      vasomotion, the membrane potentials are slowly oscillating by about 20 mV around
      values of approximately -50 mV in perfect synchrony with vasomotor movements and
      depolarizing phases coincide with vasoconstrictions while polarizing ones with
      vasodilatations. Comparing all parameters, in control conditions, only the
      spontaneous vasomotion frequency was significantly higher (2.37 times higher) on
      the group treated with fish oil and persisted as such throughout all experiments.
      With topical application of the drugs mentioned above, the group treated with
      fish oil showed, for each drug concentration, a balance towards vasodilatation
      with consequent increase on arteriolar blood flow and on FCD, compared with the
      olive oil treated one. No significant changes on mean arterial pressure,
      spontaneous arteriolar vasomotion amplitude or venular diameter could be detected
      in the two groups. Our results support the concept that, in the hamster cheek
      pouch microcirculation, fish oil supplementation activates K(+) channels which
      act as the EDHF and might also increase the production of vasodilators, probably
      NO.

PMID- 17196225
TI  - Modeling of oxygen transport across tumor multicellular layers.
AB  - PURPOSE: Tumor oxygen level plays a major role in the response of tumors to
      different treatments. The purpose of this study was to develop a method of
      determining oxygen transport properties in a recently developed 3D model of tumor
      parenchyma, the multicellular layer (MCL). METHODS: OCM-1 human choroidal
      melanoma cells were grown as 3D MCLs on collagen-coated culture plate inserts. A
      recessed-cathode oxygen microelectrode was used to measure oxygen tension (PO(2))
      profiles across 8 different MCL from the free surface to the insert membrane. The
      profiles were fitted to four different one-dimensional diffusion models: 1-, 2-,
      and 3-region models with uniform oxygen consumption (q) in each region and a
      modified 3-region model with a central region where q=0 and PO(2)=0. RESULTS:
      Depending upon the presence of a central region of anoxia, the PO(2) profiles
      were fitted best by either the two-region model or the modified 3-region model.
      Consumption of tumor cells near the insert membrane was higher than that of cells
      close to the free surface (33.1+/-13.6 x 10(-4) vs. 11.8+/-6.7 x 10(-4) mm
      Hg/mum(2), respectively). CONCLUSIONS: The model is useful for determining
      oxygenation and consumption in MCL, especially for cell lines that cannot be
      grown as spheroids. In the future, this model will permit the study of parameters
      important in tumor oxygenation in vitro.

PMID- 17196227
TI  - The opposite effect of a low and a high dose of serotonin-1A agonist on behavior
      induced by MK-801.
AB  - The purpose of the present study was to investigate the opposite effect of the
      pre- and postsynaptic serotonin-1A (5-HT(1A)) receptors on the psychotic-like
      behavior induced by a non-competitive antagonist of the NMDA receptor,
      dizocilpine (MK-801). Male Wistar rats received two doses (0.025mg/kg and 1mg/kg)
      of 5-HT(1A) receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin)
      and/or MK-801 in two different doses, 0.1mg/kg or 0.3mg/kg. We measured
      sensorimotor gating by testing prepulse inhibition of acoustic startle response
      (PPI) and locomotor activity of rats. We found an opposite effect of the low and
      high 5-HT(1A) receptor agonist doses on MK-801 induced deficit in PPI and
      hyperlocomotion in habituated rats. The low dose of 8-OH-DPAT, which
      preferentially acts on presynaptic 5-HT(1A) receptors, restored the deficit in
      PPI and hyperlocomotion in MK-801 (0.1mg/kg)-treated habituated rats. However,
      the high dose of 8-OH-DPAT, which activates both pre- and postsynaptic 5-HT(1A)
      receptors, decreased PPI and increased locomotor activity after administration of
      the low dose of MK-801. Administration of 8-OH-DPAT itself dose-dependently
      decreased PPI. However, only the high dose of 8-OH-DPAT increased spontaneous
      locomotor activity of rats. Our results indicate that there is an interaction
      between the NMDA and 5-HT(1A) receptors. In addition, these findings could
      indicate that activation of the 5-HT(1A) autoreceptor could be effective as a
      treatment in schizophrenia, but full potent agonism of the receptor could worsen
      the psychotic symptoms.

PMID- 17196226
TI  - ORL1 receptor-mediated down-regulation of mPER2 in the suprachiasmatic nucleus
      accelerates re-entrainment of the circadian clock following a shift in the
      environmental light/dark cycle.
AB  - The circadian pacemaker in the suprachiasmatic nucleus (SCN) generates the near
      24-h period of the circadian rhythm and is entrained to the 24-h daily cycle by
      periodic environmental signals, such as the light/dark cycle (photic signal), and
      can be modulated by various drugs (non-photic signals). The mechanisms by which
      non-photic signals modulate the circadian clock are not well understood in mice.
      In mice, many reportedly non-photic stimuli have little effect on the circadian
      rhythm in vivo. Herein, we investigated the molecular mechanism in W-212393
      induced phase advance using mice. W-212393 caused a significant phase advance of
      locomotor activity rhythm in mice at subjective day. Injection of W-212393 during
      subjective day elicited down-regulation of mPER2 protein in the SCN shell region,
      but not mPer2 mRNA. Administration of W-212393 during subjective day failed to
      produce phase advance in mPer2-mutant mice as well as in ORL1 receptor deficient
      mice. Furthermore, we show that such inhibition of mPER2 accelerates re
      entrainment of the circadian clock following an abrupt shift in the environmental
      light/dark cycle, such as occurs with transmeridian flight. The present results
      suggest that post-translational down-regulation of mPER2 protein in the shell
      region of mouse SCN may be involved in W-212393-induced non-photic phase advance.

PMID- 17196228
TI  - Physical training in developing rats does not influence the kindling development
      in the adult life.
AB  - The positive effect of physical exercise programs on seizure frequency and
      severity has been demonstrated both in adult human and animals. However, this
      investigation during animal brain development has not been examined. To this
      purpose, the present work was aimed to analyse the effect of physical exercise
      training in rats after weaning on the kindling process in the adulthood. Thirty
      rats were divided into 3 groups: the first group (EX=10) was submitted to daily
      bout of aerobic exercise (60 min running on the treadmill at 24/26 m/min) between
      P21 and 60 days of age. After this period of training, animals were submitted to
      60 min running at the same speed and kindling stimulated one min post-exercise.
      The second group (SHAM=10) was maintained in the treadmill for the same time as
      the trained group without being submitted to physical exercise. The third group
      served as control (CTL=10). The number of stimulations required to reach stage 5
      for the EX group was not statistically different from CTL and SHAM groups.
      However, the EX group spent a longer time and a shorter afterdischarge (AD) in
      stage 1 compared to the CTL and SHAM groups. The number of stimulations and AD
      duration in stage 2, 3 and 4 was not statistically different between all the
      groups. Taken together, our study showed that although forced physical exercise
      in developing rats does not exert significant influence to reach the stage 5 of
      amygdala kindling in the adult life its interference during the process of
      epileptogenesis indicate a positive effect of exercise in developing brain.

PMID- 17196229
TI  - Feeding entrainment of locomotor activity rhythms, digestive enzymes and
      neuroendocrine factors in goldfish.
AB  - The existence of food anticipatory activity (FAA) in animals subjected to daily
      feeding schedules seems to be mediated by a feeding-entrainable oscillator (FEO).
      Such an FEO may help in anticipating meal time and so optimizing food acquisition
      and nutrient utilization. In this study we investigated the existence of FAA and
      whether digestive enzymes, plasma cortisol, hypothalamic NPY and gastrointestinal
      tract (GIT) and plasma melatonin were entrained by periodic feeding in goldfish.
      We observed that periodically fed goldfish showed FAA in locomotor activity as
      well as in amylase and NPY. Alkaline protease and GIT melatonin were higher after
      feeding, whereas plasma cortisol levels were reduced. Plasma melatonin remained
      unmodified before and after meal time. These results suggested that scheduled
      feeding entrained both behavioral and certain physiological patterns in goldfish,
      FAA being of adaptive value to anticipate a meal and prepare the digestive
      physiology of fish.

PMID- 17196230
TI  - Prevalence of beta-thalassaemia in subcastes of Indian Sindhis: Results from a
      two-phase survey.
AB  - OBJECTIVE: To estimate the prevalence of beta-thalassaemia in different subcastes
      of the Indian Sindhi population who, in general, have a high prevalence of this
      disease. STUDY DESIGN: A two-phase, community-based survey. METHODS:
      Asymptomatic, Sindhi volunteers from Nagpur, central India, were recruited into
      the present study over a 7-year period. The first phase included the use of the
      Naked Eye Single Tube Red cell Osmotic Fragility Test (NESTROFT). Those positive
      for NESTROFT or those volunteering for haemoglobin A(2) (HbA(2)) quantification
      entered the second phase of the survey. Appropriate statistical methods for
      estimating prevalence from two-phase surveys were used. RESULTS: The prevalence
      of beta-thalassaemia carriers across the five major Sindhi subcastes varied
      substantially in the study population. Larkana Sindhis had the highest (17%)
      whereas Dadu Sindhis had the lowest (8%) frequency of the beta-thalassaemia
      allele. As a corollary, the projected incidence of beta-thalassaemia major in
      newborn babies greatly varied by the subcastes of the parents. CONCLUSION: Ethnic
      subgroups within populations known to commonly carry the beta-thalassaemia gene
      provide further information that is useful from epidemiological and public health
      perspectives.

PMID- 17196231
TI  - Correlation between the nature of immunity induced by different immunogens and
      the establishment of latent infection by wild-type pseudorabies virus.
AB  - To assess the correlation between the nature of immunity induced by different
      types of immunogens and the establishment of latent infection by wild-type
      pseudorabies virus (PrV), we used a murine model immunized with different
      immunogens, the PrV modified live vaccine (MLV), inactivated vaccine (IAV), and
      commercial oil-adjuvant subunit vaccine (OSV), via either intranasal (i.n.) or
      intramuscular (i.m.) route. Both MLV and IAV induced a different nature of
      immunity biased to Th1- and Th2-type, respectively, as judged by the ratio of PrV
      specific IgG isotypes (IgG2a/IgG1) and the profile of cytokine IL-2, IL-4, and
      IFN-gamma production. In contrast, the OSV induced a lower isotype IgG2a to IgG1
      ratio and higher level of IL-2 production. The MLV (inducing Th1-type) provided
      more effective protection against a virulent wild-type PrV challenge than IAV and
      OSV (inducing Th2- and mixed type, respectively). In addition, the MLV impeded
      the establishment of a latent infection with wild-type PrV, and the decrease in
      the PrV latency load by immunization with the MLV appeared to be mediated by the
      immune T-cells. These results demonstrate the substantial role of the immune
      responses driven by preceding vaccination in modulating the establishment of PrV
      latency caused by the post-infection of a field virus.

PMID- 17196232
TI  - EGCG-targeted p57/KIP2 reduces tumorigenicity of oral carcinoma cells: role of c
      Jun N-terminal kinase.
AB  - The green tea polyphenol epigallocatechin-3-gallate (EGCG) regulates gene
      expression differentially in tumor and normal cells. In normal human primary
      epidermal keratinocytes (NHEK), one of the key mediators of EGCG action is
      p57/KIP2, a cyclin-dependent kinase (CDK) inhibitor. EGCG potently induces p57 in
      NHEK, but not in epithelial cancer cells. In humans, reduced expression of p57
      often is associated with advanced tumors, and tumor cells with inactivated p57
      undergo apoptosis when exposed to EGCG. The mechanism of p57 induction by EGCG is
      not well understood. Here, we show that in NHEK, EGCG-induces p57 via the p38
      mitogen-activated protein kinase (MAPK) signaling pathway. In p57-negative tumor
      cells, JNK signaling mediates EGCG-induced apoptosis, and exogenous expression of
      p57 suppresses EGCG-induced apoptosis via inhibition of c-Jun N-terminal kinase
      (JNK). We also found that restoration of p57 expression in tumor cells
      significantly reduced tumorigenicity in athymic mice. These results suggest that
      p57 expression may be an useful indicator for the clinical course of cancers, and
      could be potentially useful as a target for cancer therapies.

PMID- 17196233
TI  - The effect of stress on the acute neurotoxicity of the organophosphate
      insecticide chlorpyrifos.
AB  - A study was conducted to determine if multiple exposures to several stress
      paradigms might affect the anticholinesterase effect of subsequently administered
      organophosphate insecticide chlorpyrifos. Male Sprague-Dawley rats were subject
      to daily periods of restraint, swimming, a combination of the two, or neither of
      the two (controls) (n=8/group) for 5 days per week over a six-week period. The
      most profound stress, as measured by reduced body weight gain and elevated levels
      of plasma corticosterone, was swimming. On day 39 of the study, shortly after the
      daily stress episode, one half of the rats in each group was dosed with 60 mg/kg
      chlorpyrifos subcutaneously. This had no effect on subsequent levels of plasma
      corticosterone. There were no stress-related differences in the degree of
      chlorpyrifos-induced inhibition of brain acetylcholinesterase in animals
      sacrificed on day 43.

PMID- 17196234
TI  - Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium
      in mice chronically exposed to lead correlates with a shift to Th2-type immune
      responses.
AB  - Persistent exposure to inorganic lead (Pb) is known to adversely affect the
      immune system. In the present study, we assessed the effect of chronic Pb
      exposure on susceptibility to infection by the facultative intracellular pathogen
      Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in
      drinking water for approximately 16 weeks, resulting in a significant level of Pb
      in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to
      Salmonella infection, manifested by increased bacterial burden in target organs
      and heightened mortality. Flow cytometric analysis of the splenic cellular
      composition in normal and Pb-exposed mice revealed no gross alteration in the
      ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and
      T cells to upregulate the expression of activation antigens in response to
      mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of
      the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a
      marked reduction in IFN-gamma and IL-12p40 production associated with Pb
      exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3-
      to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4
      correlated with a shift in the in vivo anti-Salmonella antibody response from the
      protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that
      chronic exposure to high levels of Pb results in a state of immunodeficiency
      which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather
      is largely caused by a shift in immune responsiveness to Th2-type reactions.

PMID- 17196235
TI  - Urinary arsenic profile affects the risk of urothelial carcinoma even at low
      arsenic exposure.
AB  - Arsenic exposure is associated with an increased risk of urothelial carcinoma
      (UC). To explore the association between individual risk and urinary arsenic
      profile in subjects without evident exposure, 177 UC cases and 313 age-matched
      controls were recruited between September 2002 and May 2004 for a case-control
      study. Urinary arsenic species including the following three categories,
      inorganic arsenic (As(III)+As(V)), monomethylarsonic acid (MMA(V)) and
      dimethylarsinic acid (DMA(V)), were determined with high-performance liquid
      chromatography-linked hydride generator and atomic absorption spectrometry.
      Arsenic methylation profile was assessed by percentages of various arsenic
      species in the sum of the three categories measured. The primary methylation
      index (PMI) was defined as the ratio between MMA(V) and inorganic arsenic.
      Secondary methylation index (SMI) was determined as the ratio between DMA(V) and
      MMA(V). Smoking is associated with a significant risk of UC in a dose-dependent
      manner. After multivariate adjustment, UC cases had a significantly higher sum of
      all the urinary species measured, higher percent MMA(V), lower percent DMA(V),
      higher PMI and lower SMI values compared with controls. Smoking interacts with
      the urinary arsenic profile in modifying the UC risk. Differential carcinogenic
      effects of the urinary arsenic profile, however, were seen more prominently in
      non-smokers than in smokers, suggesting that smoking is not the only major
      environmental source of arsenic contamination since the UC risk differs in non
      smokers. Subjects who have an unfavorable urinary arsenic profile have an
      increased UC risk even at low exposure levels.

PMID- 17196236
TI  - Contributions of reactive oxygen species and mitogen-activated protein kinase
      signaling in arsenite-stimulated hemeoxygenase-1 production.
AB  - Hemeoxygenase-1 (HO-1) is an oxidative stress responsive gene upregulated by
      various physiological and exogenous stimuli. HO-1 has cytoprotective activities
      and arsenite is a potent inducer of HO-1 in many cell types and tissues,
      including epidermal keratinocytes. We investigated the potential contributions of
      reactive oxygen species (ROS) generation and mitogen-activated protein kinase
      (MAPK) activation to arsenite-dependent regulation of HO-1 in HaCaT cells, an
      immortalized human keratinocyte line. Both epidermal growth factor (EGF) and
      arsenite stimulated ROS production was detected by dihydroethidium (DHE) staining
      and fluorescence microscopy. Arsenite induced HO-1 in a time- and concentration
      dependent manner, while HO-1 expression in response to EGF was modest and evident
      at extended time points (48-72 h). Inhibition of EGF receptor, MEK I/II or Src
      decreased arsenite-stimulated HO-1 expression by 20-30%. In contrast, addition of
      a superoxide scavenger or inhibition of p38 activity decreased the arsenite
      dependent response by 80-90% suggesting that ROS and p38 are required for HO-1
      induction. However, ROS generation alone was insufficient for the observed
      arsenite-dependent response as use of a xanthine/xanthine oxidase system to
      generate ROS did not produce an equivalent upregulation of HO-1. Cooperation
      between ERK signaling and ROS generation was demonstrated by synergistic
      induction of HO-1 in cells co-treated with EGF and xanthine/xanthine oxidase
      resulting in a response nearly equivalent to that observed with arsenite. These
      findings suggest that the ERK/MAPK activation is necessary but not sufficient for
      optimal arsenite-stimulated HO-1 induction. The robust and persistent
      upregulation of HO-1 may have a role in cellular adaptation to chronic arsenic
      exposure.

PMID- 17196237
TI  - Acute effects of an anatoxin-a producing cyanobacterium on juvenile fish-Cyprinus
      carpio L.
AB  - The worldwide increase of eutrophication in fresh water bodies has caused
      cyanobacterial blooms to be more frequent. Anatoxin-a is a potent neurotoxin
      known to be produced by several genera of cyanobacteria including Anabaena. In
      this work, we exposed juvenile carps to freeze-dried cells of a toxic strain of
      the cyanobacterium Anabaena sp. during a 4-day period. Two different cell density
      -10(5) and 10(7) cell ml(-1)--were assayed. Lethality and anatoxin-a
      concentration in the whole fish were determined. In the higher cell density, all
      fish died between 26 and 29 h after exposure to toxin, whereas in the 10(5) cell
      ml(-1) density no deaths were observed. Levels of anatoxin-a in the whole fish
      ranged between 0.031 microg g(-1)d.w. at the 10(5) cell ml(-1) concentration and
      0.768 microg g(-1)d.w. at 10(7) cell ml(-1). Minor uptake of anatoxin-a occurred.

PMID- 17196238
TI  - The universal algorithm of maturation for secretory and excretory protein
      precursors.
AB  - During maturation, most proteins undergo different posttranslational
      modifications. In most simple cases, signal peptidases remove the signal or
      leader peptide from the precursors of the secretory proteins during their
      translocation across the ER membrane. For biologically active proteins, such as
      enzymes, regulatory and defense proteins, toxins, etc., additional maturation
      regulating mechanisms were shown to proceed with limited proteolysis of inactive
      precursors by specific enzymes. A number of specific enzymes from different cell
      types selectively cleave proproteins at specific processing sites. In this work,
      we analyzed the sequences of protein precursors synthesized in the excretory
      glands of different animals and identified new, non-traditional processing sites.
      They differ from the motifs previously identified in secreted proteins'
      precursors and enabled us to reconstruct the sequence of events leading to the
      conversion of protein precursors into the final products (mature proteins). We
      also found that in animals, the maturation mechanism of secretory and excretory
      proteins and the set of enzymes involved are species specific. The processing
      sites identified in protein precursors in this study are useful for a more
      detailed genome analysis and more accurate mature protein sequence prediction.

PMID- 17196239
TI  - Bone breccias, bone dumps, and sedimentary sequences of the western Limeworks,
      Makapansgat, South Africa.
AB  - The sediments in the western side of the Makapansgat Limeworks were either
      precipitated as speleothems, represented in the earlier massive deposits, or were
      deposited as coarsening clastic sediments, mainly representing later deposits.
      Between the earlier deposits and the main sedimentary phase, the stratigraphic
      sequence was inverted twice to a considerable height by the unusual deposition of
      subaqueous speleothem. Bone-bearing deposits, including the Main Quarry Bone
      Breccia and the well-known Grey Breccia belong, in time, to the lower part of the
      clastic deposits called the Red Silts. Australopith fossils have been found in
      the Grey Breccia dumped material and, in situ, from the dolomite clast breccia on
      the Main Quarry entrance buttress. Whatever the problems may be in provenancing
      some of the material from the Limeworks dumps, there is no doubt that the three
      rows of blocks on the southern side of the dumps belong to the Grey Breccia, and
      other rows contain red sediment sufficient for them to be safely associated with
      the Red Silts. There is no reason why this material should not be prepared with
      confidence as to its stratigraphic provenance. In any case, stratigraphic
      evidence, presented here, shows that there is little difference in time between
      the deposition of the bone-bearing breccias.

PMID- 17196240
TI  - Candidate genes affecting Drosophila life span identified by integrating
      microarray gene expression analysis and QTL mapping.
AB  - The current increase in life expectancy observed in industrialized societies
      underscores the need to achieve a better understanding of the aging process that
      could help the development of effective strategies to achieve healthy aging. This
      will require not only identifying genes involved in the aging process, but also
      understanding how their effects are modulated by environmental factors, such as
      dietary intake and life style. Although the human genome has been sequenced, it
      may be impractical to study humans or other long-lived organisms to gain a
      mechanistic understanding about the aging process. Thus, short-lived animal
      models are essential to identifying the mechanisms and genes that affect the rate
      and quality of aging as a first step towards identifying genetic variants in
      humans. In this study, we investigated gene expression changes between two
      strains of Drosophila (Oregon and 2b) for which quantitative trait loci (QTLs)
      affecting life span were identified previously. We collected males and females
      from both strains at young and old ages, and assessed whole genome variation in
      transcript abundance using Affymetrix GeneChips. We observed 8217 probe sets with
      detectable transcripts. A total of 2371 probe sets, representing 2220 genes,
      exhibited significant changes in transcript abundance with age; and 839 probe
      sets were differentially expressed between Oregon and 2b. We focused on the 359
      probe sets (representing 354 genes) that exhibited significant changes in gene
      expression both with age and between strains. We used these genes to integrate
      the analysis of microarray gene expression data, bioinformatics, and the results
      of genetic mapping studies reported previously, to identify 49 candidate genes
      and four pathways that could potentially be responsible for regulating life span
      and involved in the process of aging in Drosophila and humans.

PMID- 17196241
TI  - A simplified method for estimation of jarosite and acid-forming sulfates in acid
      mine wastes.
AB  - In acid base accounting (ABA) estimates of acid mine wastes, the acid potential
      (AP) estimate can be improved by using the net carbonate value (NCV) reactive
      sulfide S method rather than total S assay methods but this does not give
      recovery of potentially acid producing ferrous and ferric sulfates present in
      many wastes. For more accurate estimation of AP, an effective, site-specific
      method to quantify acid sulfate salts, such as jarosite and melanterite, in waste
      rocks has been developed and tested on synthetic and real wastes. The SPOCAS
      (acid sulfate soils) methods have been modified to an effective, rapid method to
      speciate sulfate forms in different synthetic waste samples. A three-step
      sequential extraction procedure has been established. These steps are: (1) argon
      purged water extraction (3 min) to extract soluble Fe(II) salts (particularly
      melanterite), epsomite and gypsum (<10 wt.%), (2) roasting at 550 degrees C (1 h)
      to remove sulfur from pyrite and other reactive sulfides, (3) HCl extraction (4
      M, 30 min) for determination of jarosites. Products (solid and aqueous) have been
      characterized at each step including the jarosite decomposition process in Step 2
      where temperature control is critical to avoid S loss. The sequential extraction
      procedure was used to quantitatively determine melanterite, epsomite, gypsum,
      pyrite and jarosite concentrations in a synthetic waste sample containing these
      mineral phases at 5 wt.% in quartz, and also tested using a tailings waste sample
      to quantitatively determine epsomite, gypsum and jarosite contents. The method is
      applicable to most waste samples including those with non-pyrite sulfides but for
      samples containing significant amounts of sulfur (>1 wt.% S) as copper sulfides,
      the second step of roasting needs to be excluded from the procedure with an
      increased time of 4 M HCl extraction to 16 h for jarosite determination.

PMID- 17196242
TI  - Unexpectedly high rates of grade 3 and 4 acute toxicity in the treatment of
      cervical cancer in sub-Saharan Africa.

PMID- 17196243
TI  - Increased nicotine self-administration following prenatal exposure in female
      rats.
AB  - There is a significant association between maternal cigarette smoking during
      pregnancy and greater subsequent risk of smoking in female offspring. In animal
      models, prenatal nicotine exposure causes persistent alterations in cholinergic
      and monoaminergic systems, both of which are important for nicotine actions
      underlying tobacco addiction. Accordingly, the current study was conducted to
      determine if there is a cause-and-effect relationship between prenatal nicotine
      exposure and nicotine self-administration starting in adolescence. Pregnant rats
      were administered nicotine (6 mg/kg/day) by osmotic minipump infusion throughout
      gestation and then, beginning in adolescence and continuing into adulthood,
      female offspring were given access to nicotine via a standard operant IV self
      administration procedure (0.03 mg/kg/infusion). Gestational nicotine exposure did
      not alter the initial rate of nicotine self-administration. However, when animals
      underwent one week of forced abstinence and then had a second opportunity to self
      administer nicotine, the prenatally-exposed animals showed a significantly
      greater rate of self-administration than did the controls. Prenatal nicotine
      exposure causes increased nicotine self-administration, which is revealed only
      when the animals are allowed to experience a period of nicotine abstinence. This
      supports a cause-and-effect relationship between the higher rates of smoking in
      the daughters of women who smoke cigarettes during pregnancy and implicates a
      role for nicotine in this effect. Our results further characterize the long-term
      liabilities of maternal smoking but also point to the potential liabilities of
      nicotine-based treatments for smoking cessation during pregnancy.

PMID- 17196244
TI  - Prednisolone reduces recurrent wheezing after a first wheezing episode associated
      with rhinovirus infection or eczema.
AB  - BACKGROUND: Rhinovirus-induced early wheezing has been suggested as a new
      important risk factor for recurrent wheezing. OBJECTIVE: We sought to investigate
      the risk factors for recurrent wheezing and to determine post hoc the efficacy of
      prednisolone in risk groups. METHODS: We followed for 1 year 118 children (median
      age, 1.1 years) who had had their first episode of wheezing and had participated
      in a trial comparing prednisolone with placebo in hospitalized children.
      Demographics and laboratory data were obtained at study entry. The follow-up
      outcome was recurrent wheezing (3 physician-confirmed episodes). RESULTS:
      Recurrent wheezing was diagnosed in 44 (37%) children. Independent risk factors
      were age < 1 year, atopy, and maternal asthma. The probability of recurrent
      wheezing was higher in rhinovirus than respiratory syncytial virus (RSV)-affected
      children among placebo recipients (hazard ratio, 5.05; 95% CI, 1.00-25.41).
      Prednisolone decreased the probability of recurrent wheezing in children with
      eczema (0.15; 95% CI, 0.04-0.63) but not in those without eczema (1.89; 95% CI,
      0.83-4.29; P = .007 for interaction). Prednisolone was associated with less
      recurrent wheezing in the rhinovirus group (0.19; 95% CI, 0.05-0.71), but not in
      the RSV (2.12; 95% CI, 0.46-9.76) or in the RSV/rhinovirus-negative groups (2.03;
      95% CI, 0.83-5.00; P = .017 for interaction). CONCLUSION: Rhinovirus-induced
      early wheezing is a major viral risk factor for recurrent wheezing. Prednisolone
      may prevent recurrent wheezing in rhinovirus-affected first-time wheezers. The
      presence of eczema may also influence the response to prednisolone. CLINICAL
      IMPLICATIONS: A prospective trial is needed to test the hypothesis that
      prednisolone reduces recurrent wheezing in rhinovirus-affected wheezing children.

PMID- 17196245
TI  - CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy,
      X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes.
AB  - BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked
      (IPEX) results in systemic autoimmunity from birth and can be caused by mutations
      in the transcription factor forkhead box P3 (FOXP3). OBJECTIVE: To determine if
      Foxp3 is required for the generation of IL-10-expressing T regulatory cells.
      METHODS: CD4 lymphocytes were isolated from patients with IPEX-like syndromes and
      activated with antibodies to CD3 and CD46 to generate IL-10-expressing T
      regulatory cells. RESULTS: We describe a patient with clinical manifestations of
      IPEX that had a normal Foxp3 gene, but who had CD25 deficiency due to autosomal
      recessive mutations in this gene. This patient exhibited defective IL-10
      expression from CD4 lymphocytes, whereas a Foxp3-deficient patient expressed
      normal levels of IL-10. CONCLUSION: These data show that CD25 deficiency results
      in an IPEX-like syndrome and suggests that although Foxp3 is not required for
      normal IL-10 expression by human CD4 lymphocytes, CD25 expression is important.
      CLINICAL IMPLICATIONS: Any patient with features of IPEX but with a normal Foxp3
      gene should be screened for mutations in the IL-2 receptor subunit CD25.

PMID- 17196247
TI  - Determinants of colorectal cancer screening use, attempts, and non-use.
AB  - BACKGROUND: Relatively little is known about the experiences and preferences of
      users and those who attempt colorectal cancer (CRC) screening. This study
      describes factors influencing CRC screening decisions among users, attempters,
      attempter users (individuals who both attempted and completed at least one
      screening procedure), and non-users; identifies factors interfering with test
      completion; and describes correlates of screening preferences. METHODS: A
      primarily stratified random sample of patients from the University of Michigan
      Health System clinics, Ann Arbor, Michigan, with oversampling of FOBT attempters,
      completed a mailed questionnaire in fall, 2003. Descriptive and multivariate
      approaches evaluated factors influencing screening use and preferences. RESULTS:
      "Accuracy of results" was reported most often as important when deciding about
      CRC screening regardless of screening status. The importance of psychological
      decisional factors differed significantly by screening status (P<0.05). Among
      factors interfering with test completion, 38.5% attempting FOBT reported they
      "forgot" whereas 29.8% attempting colonoscopy were "afraid of pain."
      Approximately 56.3% indicated a preference for a CRC test: respondents who
      considered "discomfort" important preferred FOBT (OR: 0.39, 95% CI: 0.17, 0.87);
      those with a prior colonoscopy preferred an invasive test (OR: 6.50, 95% CI:
      2.90, 14.50). CONCLUSIONS: To improve adherence to CRC screening recommendations,
      physicians should tailor discussions to patients' prior experiences and test
      specific concerns and elicit preferences for screening.

PMID- 17196246
TI  - High-throughput fluorescent multiplex array for indoor allergen exposure
      assessment.
AB  - BACKGROUND: Current enzyme immunoassay methods for detection of common indoor
      allergens in environmental dust samples are labor-intensive and time consuming.
      OBJECTIVE: To develop and validate a fluorescent multiplex array to measure 6
      (Der p 1, Der f 1, Der p 2, Der f 2, Fel d 1, and Can f 1) indoor allergen levels
      simultaneously. METHODS: A multiplex array for 6 allergens, using mAbs covalently
      coupled to fluorescent microspheres, was developed using a single universal
      standard composed of purified natural allergens. The multiplex array was
      validated by comparing the measured dust mite, cat, and dog allergen levels in
      household dust samples to those obtained by standard ELISA methods. RESULTS:
      Linear regression analysis showed a highly significant quantitative correlation
      between the multiplex array and ELISA for dust mite, cat, and dog allergens: R(2)
      values ranging from 0.90 to 0.99 (P < .001). In addition, the sensitivity, limit
      of detection (<0.1 ng/mL), reproducibility, intra-assay coefficient of variance
      (<5%), and interassay coefficient of variance (<25%) of the fluorescent multiplex
      array were shown to be equal to or better than the ELISA method. CONCLUSION: A
      multiplex array has been developed to measure simultaneously 6 indoor allergens
      from a single sample. The array will facilitate epidemiologic studies and indoor
      air quality assessments and can, in principle, be expanded to include other
      allergens and biologics. CLINICAL IMPLICATIONS: The multiplex array lends itself
      to clinical studies, population-based environmental surveys, and allergen
      avoidance studies comparing allergen exposure in large populations over several
      time points.

PMID- 17196248
TI  - Serum concentrations of gonadotropins and steroid hormones of Neophocaena
      phocaenoides asiaeorientalis in middle and lower regions of the Yangtze River.
AB  - As a relatively isolated and unique freshwater population, the Yangtze finless
      porpoise (Neophocaena phocaenoides asiaeorientalis) is the most endangered
      subpopulation of this species. The objective of this study was to improve our
      understanding of their reproductive endocrinology by measuring (radioimmunoassay)
      serum concentrations of FSH, LH, estradiol (E(2)), progesterone (P(4)) and
      testosterone (T(2)) in free-ranging animals. Blood samples were collected from 66
      Yangtze finless porpoises (41 males and 25 females) captured in the middle and
      lower reaches of the Yangtze River. Based on significant variation of serum T(2)
      concentrations in males with body length (BL) >138 cm, we inferred that they were
      mature; in these animals, there were significant seasonal variations in serum
      T(2) concentrations, with the highest concentrations in March and April (502.0+/
      319.8 ng/dL, mean+/-S.D.) and the lowest in December (79.4+/-83.2 ng/dL). Serum
      T(2) concentrations positively correlated with serum concentrations of LH and
      weakly correlated with serum concentrations of E(2), whereas there was a
      significant negative correlation between serum LH and FSH concentrations in males
      >138 cm. The smallest apparently pregnant female porpoise had a BL of 130 cm.
      Serum P(4) concentrations ranged from 13.2 to 112.4 ng/mL (43.9+/-28.3 ng/mL) in
      pregnant females, and fluctuated under 1.0 ng/mL in non-pregnant females with
      BL>130 cm. Serum LH concentrations were significantly higher in non-pregnant
      females >130 cm versus those females <130 cm. To our knowledge, this is the first
      study of endocrine-related maturity and seasonal breeding characteristics of the
      Yangtze finless porpoise.

PMID- 17196249
TI  - In vitro and in vivo evaluation of donepezil-sustained release microparticles for
      the treatment of Alzheimer's disease.
AB  - The purpose of this work is to prepare donepezil microparticles (DM) and evaluate
      its advantage as a sustained release delivery system with subcutaneous injection
      once a month. DM was prepared using poly (d,l-lactide-co-glycolide) (PLGA) by an
      oil-water emulsion solvent evaporation technique. DM showed the loading ratio
      13.2+/-2.1% (w/w) and yield 54.8+/-0.8% with mean particle size about 75mum. In
      vitro release of DM showed that donepezil completely released within 28 days in
      water, but the cumulative release percentages up to day 30 were 98.4% and 49.1%
      for phosphate buffer saline (PBS, pH 5.8) and PBS (pH 7.4), respectively. The in
      vivo experiment demonstrated that DM (90mg/kg) produced a sustained release
      process in rats, and reached steady-state concentration at day 8 and maintained
      until day 27 with steady-state levels of donepezil between 130.3+/-7.8 and 121+/
      9.8ng/ml, which was accordance with that of free donepezil by oral application
      route (3mg/kgday). DM (90mg/kg) by subcutaneous infusion in rats produced the
      same pharmacological role as free donepezil (3mg/kgday) by oral application
      route. These results implicated that DM as a sustained release delivery strategy
      could substitute for its oral formulation for therapy of AD and come true its
      administration once a month.

PMID- 17196250
TI  - Branched polyesters based on poly[vinyl-3-(dialkylamino)alkylcarbamate-co-vinyl
      acetate-co-vinyl alcohol]-graft-poly(d,l-lactide-co-glycolide): effects of
      polymer structure on cytotoxicity.
AB  - Branched polyesters of the general structure poly[vinyl-3
      (dialkylamino)alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(d,l
      lactide-co-glycolide) have shown potential for nano- and micro-scale drug
      delivery systems. For further optimization of this polymer class their
      cytotoxicity needs to be characterized establishing structure-toxicity
      relationships. Effects of type and degree of amine substitution as well as
      molecular weight on cytotoxicity were evaluated in L929 mouse fibroblasts using a
      MTT assay whereas interactions with cell membranes were quantified by LDH release
      and caspase (3/7)-activation. Finally, direct cell-polymer contact assays were
      conducted. Ungrafted amine-modified polymer backbone yielded IC(50) values in the
      range of 0.05-10mg/ml. Generally higher toxicities were observed with an
      increasing degree of amine substitution. Amine substituents could be ranked as
      diethylaminopropylamine (DEAPA)<diethylaminoethylamine
      (DEAEA)<dimethylaminopropylamine (DMAPA) but the degree of amine substitution was
      more dominant than the type of amine function. Membrane interactions seem to
      cause necrotic cell reactions in a dose-dependent manner for highly charged amine
      poly(vinyl alcohol) (PVA) backbones. To attenuate cytotoxic effects DEAPA-PVA
      backbones were grafted with biodegradable PLGA side chains at molecular ratios of
      1:10 and 1:20. Cytotoxicity of extracts of these polymers was significantly lower
      compared to ungrafted polymers possibly caused by shielding of polycationic
      backbone with hydrophobic PLGA side chains. P(33)-20, a polymer containing a
      sufficiently high degree of amine substitution could serve as a lead candidate
      for further investigations. In conclusion, structure-toxicity relationships could
      be established and shielding the polycationic backbone using PLGA side chains
      seems to be a promising strategy meriting further investigations.

PMID- 17196252
TI  - Animal models of human placentation--a review.
AB  - This review examines the strengths and weaknesses of animal models of human
      placentation and pays particular attention to the mouse and non-human primates.
      Analogies can be drawn between mouse and human in placental cell types and genes
      controlling placental development. There are, however, substantive differences,
      including a different mode of implantation, a prominent yolk sac placenta, and
      fewer placental hormones in the mouse. Crucially, trophoblast invasion is very
      limited in the mouse and transformation of uterine arteries depends on maternal
      factors. The mouse also has a short gestation and delivers poorly developed
      young. Guinea pig is a good alternative rodent model and among the few species
      known to develop pregnancy toxaemia. The sheep is well established as a model in
      fetal physiology but is of limited value for placental research. The ovine
      placenta is epitheliochorial, there is no trophoblast invasion of uterine
      vessels, and the immunology of pregnancy may be quite different. We conclude that
      continued research on non-human primates is needed to clarify embryonic
      endometrial interactions. The interstitial implantation of human is unusual, but
      the initial interaction between trophoblast and endometrium is similar in
      macaques and baboons, as is the subsequent lacunar stage. The absence of
      interstitial trophoblast cells in the monkey is an important difference from
      human placentation. However, there is a strong resemblance in the way spiral
      arteries are invaded and transformed in the macaque, baboon and human. Non-human
      primates are therefore important models for understanding the dysfunction that
      has been linked to pre-eclampsia and fetal growth restriction. Models that are
      likely to be established in the wake of comparative genomics include the
      marmoset, tree shrew, hedgehog tenrec and nine-banded armadillo.

PMID- 17196251
TI  - Thyroid hormone (T3)-modification of polyethyleneglycol (PEG)-polyethyleneimine
      (PEI) graft copolymers for improved gene delivery to hepatocytes.
AB  - Targeting of gene vectors to liver hepatocytes could offer the opportunity to
      cure various acquired and inherited diseases. Efficient gene delivery to the
      liver parenchyma has been obscured from efficient targeting of hepatocytes. Here
      we show that the thyroid hormone, triiodothyronine (T3), can be used to improve
      the gene transfer efficiency of nonviral gene vectors to hepatocytes in vitro and
      to the liver of mice in vivo. T3 conjugated to the distal ends of fluorescent
      labeled PEG-g-dextran resulted in T3-specific cellular endosomal uptake into the
      hepatocellular cell line HepG2. PEG-g-PEI graft copolymers with increasing molar
      PEG-ratios were synthesized, complexed with plasmid DNA, and transfected into
      HepG2 or HeLa cells. Gene transfer efficiency decreased as the number of PEG
      blocks increased. T3 conjugation to PEI and the distal ends of PEG blocks
      resulted in T3 specific gene transfer in HepG2 cells as evidenced by reduction of
      gene transfer efficiency after pre-incubation of cells with excess of T3. In vivo
      application of T3-PEG-g-PEI based gene vectors in mice after tail vein injection
      resulted in a significantly 7-fold increase of gene expression in the liver
      compared with PEG-g-PEI based gene vectors.

PMID- 17196253
TI  - Acid mine drainage pollution in the Tinto and Odiel rivers (Iberian Pyrite Belt,
      SW Spain) and bioavailability of the transported metals to the Huelva Estuary.
AB  - The Tinto and Odiel rivers are seriously affected by acid mine drainage (AMD)
      from the long-term mining activities in Iberian Pyrite Belt (IPB). As a
      consequence, the Huelva estuary is heavily contaminated by metals and metalloids.
      This study presents an estimation of the seasonal variation, and the dissolved
      contaminant load transported by both rivers from February 2002 to September 2004.
      Besides, toxicity and bioaccumulation tests with the sediments of the estuary
      have been conducted in order to measure the mobility of the toxic metals. Results
      show that the Tinto and Odiel rivers transport enormous quantities of dissolved
      metals to the estuary: 7900 t yr(-1) of Iron (Fe), 5800 t yr(-1) Aluminium (Al),
      3500 t yr(-1) Zinc (Zn), 1700 t yr(-1) Copper (Cu), 1600 t yr(-1) Manganese (Mn)
      and minor quantities of other metals and metalloids. These values represent 37%
      of the global gross flux of dissolved Zn transported by rivers in to the ocean,
      and 15% of the global gross flux of dissolved Cu. These metals and metalloids
      usually sink in the estuarine sediments due to pH and salinity changes. The
      increase of salinity in the estuary favours the adsorption and trapping of
      metals. For this reason, the mobility and bioavailability of metals such as Zn,
      Cd and Cu is higher in sediments located in the area of fresh water influence
      that in sediments located in the marine influenced area of the estuary, showing a
      higher percentage of fractionation and bioaccumulation of these metals in the
      station influenced by the fresh water environment.

PMID- 17196254
TI  - Family saliva sharing behaviors and age of human herpesvirus-6B infection.
AB  - OBJECTIVE: Transmission of human herpesvirus (HHV-6) type B is hypothesized to
      occur via saliva. We sought to determine whether behaviors promoting saliva
      sharing were associated with HHV-6B infection. METHODS: Parents of young children
      participating in a natural history study of HHV-6B were asked to complete a
      questionnaire focused on family behaviors that result in saliva sharing. RESULTS:
      Of 111 surveys, 109 (98%) were completed. Of the 109 participants, 37 (34%) were
      infected with HHV-6 before 1 year of age. Having older siblings (adjusted OR 4.1,
      95% CI 1.5, 11.8) and receipt of parental saliva when kissed (adjusted OR 5.1,
      95% CI 1.8, 14.5) were independently associated with younger age of HHV-6
      infection. Dose-response relationships were demonstrated between HHV-6 infection
      before 1 year and both number of siblings and the frequency that the child
      received parental saliva when being kissed (p=0.006 and p=0.002, respectively).
      CONCLUSIONS: Having older siblings and parents who shared saliva increased risk
      of HHV-6B acquisition in children. These data support the hypothesis that HHV-6
      is transmitted primarily via saliva within families.

PMID- 17196256
TI  - Fetal growth restriction is associated with reduced FasL expression by decidual
      cells.
AB  - The Fas-Fas ligand (FasL) system contributes to immune tolerance at the feto
      maternal site and has been ascribed a role in implantation and placental
      development by regulating trophoblast invasion and spiral artery remodelling. In
      the present study, we have examined FasL expression in decidual tissue from
      pregnancies with impaired placental development. Women with pre-eclampsia (PE)
      and/or fetal growth restriction (FGR) were enrolled as cases (n=33), and women
      with normal pregnancies were used as controls (n=27). Decidua basalis tissue was
      obtained by vacuum suction of the placental bed after delivery. FasL expression
      by extravillous trophoblasts (EVTs) and decidual cells (DeCs), together with EVT
      apoptosis, were assessed by immunohistochemistry. Levels of soluble FasL in
      maternal serum and apoptosis-related gene expression in decidual tissue were
      determined. The proportion of FasL-expressing DeCs was high in controls (72.0+/
      10.2%), with a significant reduction among cases (58.1+/-19.7%; p=0.002),
      especially in those with FGR (54.3+/-19.9%; p<0.001). EVTs had a lower proportion
      of FasL expression than DeCs, with a less pronounced reduction in cases compared
      to controls (10.9+/-3.9 and 8.3+/-4.0%, respectively; p=0.02). Decidual FasL
      expression correlated with placental growth. The EVT apoptosis rate did not
      differ between cases and controls (1.1+/-1.9 and 1.1+/-1.3%, respectively). These
      findings indicate a reduction of immune privilege in decidua of PE/FGR
      pregnancies by reduced FasL expression and that DeCs may have a central role in
      the Fas-FasL-based feto-maternal immune balance.

PMID- 17196255
TI  - A method to capture six-degrees-of-freedom mechanical measurements of isometric
      shoulder and elbow torques during event-related fMRI.
AB  - Functional magnetic resonance imaging (fMRI) experiments investigating cortical
      activity while controlling task performance are difficult to conduct due to the
      high magnetic field environment and a lack of compatible measurement tools. We
      describe a method to measure the generation of isometric shoulder and elbow
      torques with a six-degrees-of-freedom (DOF) load cell during an event-related
      fMRI study. Feasibility of this method is demonstrated by finding cortical
      activity on the motor cortices in a participant during an event-related study of
      shoulder abduction and elbow flexion. The described methodology permits
      researchers to control and measure intersubject and intrasubject motor task
      performance during event-related brain imaging.

PMID- 17196257
TI  - Innate immune function of the human decidual cell at the maternal-fetal
      interface.
AB  - The aim of the study was to investigate the innate immune function of decidual
      cells from term unlabored pregnancies by determining Toll-like receptor presence
      and function. Using immunohistochemistry, reverse transcriptase polymerase chain
      reaction and NF-kappaB-luciferase plasmid transfection, Toll-like receptor
      presence and function was determined. Decidual cells express Toll-like receptors
      1, 2, 4 and 6 which respond to lipopolysaccharide and peptidoglycan stimulation
      producing Interleukin-8. Decidual cells from women at term have innate immune
      function and are capable of producing Interleukin responses to bacterial ligands.

PMID- 17196258
TI  - Detection of vascular endothelial growth factor (VEGF) and VEGF receptors Flt-1
      and KDR in canine mastocytoma cells.
AB  - Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis
      and a potential autocrine growth factor for neoplastic cells in various
      malignancies. In the present study, we have investigated expression of VEGF and
      VEGF receptors in canine mastocytomas and the canine mastocytoma cell line C2. As
      assessed by immunostaining of tissue sections and cytospin slides, primary
      neoplastic mast cells (MC) and C2 cells were found to express the VEGF protein.
      In Northern blot and RT-PCR experiments, C2 cells expressed VEGF mRNA in a
      constitutive manner. VEGF mRNA expression in C2 cells was counteracted by
      LY294002 and rapamycin, suggesting involvement of the PI3-kinase/mTOR pathway.
      Moreover, C2 cells were found to express VEGF receptor-1 (Flt-1) and VEGF
      receptor-2 (KDR). However, recombinant VEGF failed to promote (3)H-thymidine
      uptake in C2 cells, and a neutralizing anti-VEGF antibody (bevacizumab) failed to
      downregulate spontaneous proliferation in these cells. In addition, rapamycin
      decreased the expression of VEGF in C2 cells at the mRNA and protein level
      without suppressing their proliferation. Together, canine mastocytoma cells
      express VEGF as well as VEGF receptors. However, despite co-expression of VEGF
      and its receptors, VEGF is not utilized as an autocrine growth regulator by
      canine mastocytoma cells.

PMID- 17196259
TI  - Hyperthermia differentially regulates TLR4 and TLR2-mediated innate immune
      response.
AB  - Fever influences multiple parameters of the immune response. However, the
      mechanisms by which fever manipulates immune response remain undefined. Here we
      present the evidences that fever range hyperthermia differentially regulates
      immune response to lipopolysaccharide (LPS) and lipoteichoic acids (LTA) through
      modulating Toll-like receptor (TLR) signaling. Pretreatment with 39.5 degrees C
      temperature enhanced LPS, but not LTA, induced NF-kappaB activation and TNF
      alpha, IL-6 production in human macrophages. Consistently, expression of TLR4,
      but not TLR2, was up-regulated by 39.5 degrees C treatment. The increase in LPS
      induced cytokine production was inhibited by TLR4-blocking antibody, indicating
      the enhancement of LPS-induced cytokine production by 39.5 degrees C pretreatment
      was TLR4-dependent. Pretreatment of mice with 39.5 degrees C temperature also
      enhanced LPS, but not LTA, induced TNF-alpha and IL-6 production in vivo. These
      results support the concept that fever range hyperthermia might activate innate
      immune response by promoting TLR4 expression and signaling, providing a possible
      mechanistic explanation for the function of fever in regulating innate immune
      responses.

PMID- 17196260
TI  - Fetal calf serum-primed dendritic cells induce a strong anti-fetal calf serum
      immune response and diabetes protection in the non-obese diabetic mouse.
AB  - In recent years, several investigators have shown that transfer of dendritic
      cells (DC) prevents diabetes development in non-obese diabetic (NOD) mice.
      Accumulating evidences showing that DC cultured in medium containing fetal calf
      serum (FCS) can induce a dominant unspecific immune response in tumor models
      after i.v. injection prompted us to investigate if the protecting effect of DC on
      diabetes development in NOD mice might be supported by the induction of an anti
      FCS immune response in recipient mice. Five-week-old NOD mice were injected i.v.
      with FCS-cultured bone marrow-derived DC or PBS as control. Levels of anti-FCS
      and anti-bovine serum albumin (BSA) antibodies were measured in the serum of
      recipient mice. Anti-FCS cellular immune responses were also analysed after a
      single DC injection using in vitro proliferation of splenocytes either in RPMI
      supplemented with FCS, AIMV-BSA or RPMI containing autologous mouse serum or BSA
      as a read out. DC injection prevented diabetes development in NOD mice and high
      titers of anti-FCS and anti-BSA antibodies were detected in serum of all DC
      injected mice. Besides, splenocytes isolated from DC-injected mice proliferated
      vigorously in the presence of bovine proteins in contrast to splenocytes isolated
      from control mice but removing bovine proteins abrogated the high level of
      proliferation of those splenocytes suggesting that lymphocytes have been primed
      against bovine proteins in vivo after DC injection. All together, our data show
      that DC transfer induced cellular and humoral anti-FCS immune responses in
      recipient NOD mice suggesting that the protective effect of DC relies on their
      unspecific immunostimulatory effects.

PMID- 17196262
TI  - Immune control by endocannabinoids - new mechanisms of neuroprotection?
AB  - The endocannabinoid system consists of cannabinoid receptors, their endogenous
      ligands and enzymes for synthesis and degradation of endocannabinoids and
      represents a local messenger system within and between the nervous and immune
      system. Apparently, the endocannabinoid system is involved in immune control and
      neuoprotection. In this review, we discuss possible mechanisms of immune control
      by endocannabinoids, which include the modulation of innate immunity, effects on
      cytokin networks, downregulation of adaptive immune response and apoptosis in
      immune cells.

PMID- 17196264
TI  - Separation of adeno-associated virus type 2 empty particles from genome
      containing vectors by anion-exchange column chromatography.
AB  - Adeno-associated virus (AAV) empty capsids typically co-purify with genome
      containing AAV2 vectors purified by column chromatography. This study describes a
      method to remove empty capsids from genome containing vector particles by anion
      exchange chromatography. The separation is based on the slightly less anionic
      character of empty particles compared to vectors. Detailed methods to achieve
      AAV2 vector purification and particle separation using cation exchange resin
      POROS 50HS followed by anion exchange resin Q-Sepharose(xl) are described.
      Chromatographic separation of AAV2 particles was achieved using gradients based
      on sodium acetate and ammonium acetate, and was optimal at pH 8.5. Efficient
      removal of particle surface nucleic acid impurities was found to be important to
      achieve good particle separation. In a large scale experiment performed using
      partially purified vector containing a mixture of 1.56 x 10(14)vg and 2.52 x
      10(15) empty capsids as a starting material, the optimized anion exchange
      chromatography method resulted in a vector peak of 1.15 x 10(14)vg containing
      0.25 x 10(14) empty capsids, corresponding to 74% vector yield and 86-fold
      reduction in empty capsids in the vector product.

PMID- 17196261
TI  - Suppressor role of rat CD8+CD45RClow T cells in experimental autoimmune uveitis
      (EAU).
AB  - To determine whether decreased regulatory T cell activity contributes to the
      pathogenesis of recurrent experimental autoimmune uveitis (EAU), we compared the
      immunoregulatory activity of CD8+CD45RClow T cells isolated from rats that had
      recovered from acute EAU with those from rats with the progressive, recurrent
      disease. Our results showed that CD8+CD45RClow T cells isolated from the
      recovered rats showed suppressive activity in vitro, whereas those from rats with
      progressive, recurrent EAU do not. Depletion of CD8+CD45RClow T cells from T
      cells used for adoptive transfer of EAU increased the pathogenic activity of the
      T cells. Co-transfer of CD8+CD45RClow T cells with uveitogenic T cells prevented
      the relapse of disease in the recipient rats. The suppressive CD8+CD45RClow T
      cells expressed increased levels of Foxp3 after stimulation in vitro with the
      autoantigen, and inhibited the production of IFN-gamma by autoreactive T cells.
      Our data indicate that the decreased suppressive activity of CD8+CD45RClow T
      cells is correlated with disease development in this autoimmune disease. Further
      studies on the biology of this T cell population should provide much needed
      insights into disease pathogenesis.

PMID- 17196265
TI  - A new quantitative real-time reverse transcriptase PCR assay and melting curve
      analysis for detection and genotyping of Ljungan virus strains.
AB  - Ljungan virus (LV), a new member of the Picornaviridae, recently isolated from
      vole species in both Sweden and the USA, is suspected to be pathogenic for humans
      as an aetiological agent in myocarditis, diabetes, neurological disease and
      perinatal disease. This study describes for the first time an RT-PCR assay that
      can identify and quantify LV infection in various tissue sample types using
      primers and two different minor-groove-binder probes targeting the 5'
      untranslated region of the LV genome. The assay, evaluated using control samples
      derived from various virus cultures and rodent tissues, allows precise
      quantification of viral load over six orders of magnitude (10(1) to 10(6) viral
      copies per assay) for all known strains of LV with high sensitivity and
      specificity. Furthermore, a melting curve analysis (MCA) was developed using two
      amplicon-specific hybridisation probes that allows rapid genotyping of different
      LV strains. These new methods provide useful tools to investigate the putative
      role of LV as a pathogen in both rodents and humans.

PMID- 17196266
TI  - Bluetongue virus detection by two real-time RT-qPCRs targeting two different
      genomic segments.
AB  - The detection of the bluetongue virus (BTV) by conventional methods is especially
      difficult and labour-intensive. Molecular diagnosis is also complex because of
      the high genetic diversity between and within the 24 serotypes of BTV. In the
      present study, two laboratories joined forces to develop and validate two new RT
      qPCRs detecting and amplifying BTV segments 1 and 5. The 2 assays detect strains
      from all 24 serotypes. They both have a detection limit of 0.01 ECE50 and all 114
      samples from BTV-free goats, sheep and cattle were negative. The two assays
      resulted in similar C(t) values when testing biological samples collected in
      sheep infected experimentally with a field strain of BTV from the Mediterranean
      basin. On average, the C(t) values obtained with the 2 methods applied to the 24
      serotypes were not significantly different from each other, but some moderate to
      high differences were seen with a few strains. Therefore these two methods are
      complementary and could be used in parallel to confirm the diagnosis of a
      possible new introduction of BTV. An RT-qPCR amplifying a fragment of the beta
      actin mRNA was also developed and validated as internal control for the
      bluetongue specific assays. The three assays described allow a reliable and rapid
      detection of BTV.

PMID- 17196267
TI  - Superiority of infectivity-based over particle-based methods for quantitation of
      drug resistant HIV-1 as inocula for cell cultures.
AB  - Performance of phenotypic assays and replication capacity assays require
      normalization of virus input. Therefore, quantitation of HIV-1 in supernatants to
      inoculate cell cultures is an important step. Since the gold standard for the
      determination of infectivity, the tissue culture infectious dose 50% (TCID50) is
      time-consuming, several other methods are in use. This study evaluated methods
      for the quantitation of drug resistant viruses in cell culture supernatants. The
      compared methods were based on the detection of viral structural components like
      genomic RNA or p24 antigen (CA-p24) (particle-based), the determination of
      reverse transcriptase (RT) activity, and methods based on the detection of viral
      infectivity like LTR-induced beta-galactosidase (beta-gal) activity and the
      TCID50 (infectivity-based). Significant correlations were observed between beta
      gal activity and TCID50, and between CA-p24 and viral RNA. RT activity did not
      correlate with any other method. However, RT activity correlated significantly
      with infectivity when non-resistant subtype-B isolates were analyzed. In contrast
      to viral infectivity, CA-p24 exhibited a long half life and accumulated in cell
      culture, resulting in decreasing ratios of infectious virions to CA-p24 over
      time. As a consequence, relative replication capacities of drug resistant viruses
      were only determined reliably if the input virus was normalized according to
      infectivity. In conclusion, RT activity seems to be feasible for non-resistant
      subtype-B viruses but may be of limited use for non-B subtypes and for drug
      resistant viruses. Methods determining infectivity are most suitable for
      quantitation of cell culture inocula, whereas particle-based assays are more
      appropriate for quantitation of virus production during an experiment.

PMID- 17196268
TI  - Assay of HIV gp41 amino acid sequence to identify baseline variation and mutation
      development in patients with virologic failure on enfuvirtide.
AB  - In this study, we retrospectively assessed a gp41 genotypic assay in 404
      enfuvirtide-naive individuals (340 clade B, 64 non-B clade) to determine the
      prevalence of baseline polymorphisms and in 41 patients virologically failing
      enfuvirtide to determine correlates of resistance to this agent. Conserved and
      polymorphic regions of gp41 were identified in clade B isolates, with 127 of 328
      codons (38.7%) being highly conserved (<1.0% variation) and 74 of 328 codons
      (22.6%) being partially conserved (1.0-5.0% variation). Polymorphisms were
      observed throughout gp41 in non-B clade virus sequences compared to the clade B
      reference strain, ranging from 53 natural substitutions in clade D to 76 in clade
      A. Insertions were common at positions 3, 105, 215 and 276. In the patients
      failing enfuvirtide, mutations were detected in the 10 amino acid region at
      positions 36-45 in all plasma virus sequences. Six additional mutations were
      selected outside of the common region which may be clinically significant at
      positions 33, 73, 75, 126, and 138. Two or three mutations at positions 36-45
      were observed in the majority of plasma virus sequences from patients with
      virologic failure following the use of enfuvirtide. Further study is required to
      determine the clinical relevance of the clade related polymorphisms and the new
      mutations identified in the patients with virologic failure.

PMID- 17196269
TI  - Effects of right-hemisphere cortical infarction and muscarinic acetylcholine
      receptor blockade on spatial visual attention performance in rats.
AB  - The syndrome of hemispatial neglect is defined as an inability to report, respond
      or orient to stimuli contralateral to a cerebral lesion despite intact elementary
      sensory or motor function. This syndrome is typically observed after lesions of
      the right cerebral cortex, and has been associated with impairment of attention.
      We studied whether visual attention performance is impaired after right
      hemisphere infarction in rats. Using a behavioural paradigm measuring spatial
      visual attention, we tested the effects of photothrombotic infarction to either
      the frontal cortex or the parietal cortex on attention performance. Since the
      cholinergic system is known to modulate attention performance, we additionally
      evaluated the role of cholinergic receptor blockade with scopolamine in our task
      paradigm. Our results show a transient response bias immediately after cortical
      infarction, with a decrease in contralesional responses and an increase in
      contralesional omissions after frontal infarction. Parietal infarction and
      systemic administration of scopolamine also resulted in a decrease in correct
      responses and an increase in omissions, but without a difference in side
      responding. In conclusion, right frontal infarction induces a transient
      impairment in contralesional spatial visual attention that we explain as left
      sided neglect. Right parietal infarction and cholinergic blockade shows non
      lateralized deficits in spatial visual attention, suggestive of global
      attentional impairment. We postulate that both effects of cortical infarction on
      attention performance may be related to cholinergic dysfunction. Our study
      confirms the role of frontal and parietal cortices in attention performance in
      rats, and corroborates the theory that attention performance is impaired in
      hemispatial neglect in human stroke patients.

PMID- 17196270
TI  - Muscimol inactivation of the septo-preoptic complex affects medial forebrain
      bundle self-stimulation only when directed at the complex's ventrolateral
      components.
AB  - Elements of the septo-preoptic basal forebrain complex, particularly the lateral
      and medial septum, the diagonal band of Broca, and the magnocellular preoptic
      area, have been linked to medial forebrain bundle (MFB) self-stimulation. This
      study examines the roles of these areas in MFB self-stimulation by temporarily
      inactivating them with 25 and 50ng doses of the GABA(A) receptor agonist
      muscimol. Changes in performance capacity and stimulation reward effectiveness
      were evaluated with the rate-frequency curve shift paradigm. When infused into
      the lateral and medial septum and the vertical limb of the diagonal band of
      Broca, both doses of muscimol were as ineffective as saline in altering either
      the rats' maximum rate of response for stimulation or the frequency required to
      maintain half-maximal response rate (required frequency). However, when infused
      into the horizontal limb of the diagonal band of Broca or the magnocellular
      preoptic area, muscimol substantially decreased maximal response rate and
      modestly increased required frequency. Changes in maximum rate were dose
      dependent, but changes in required frequency were not. Muscimol infusions
      contralateral to the stimulated hemisphere were as effective as ipsilateral
      infusions; bilateral infusions tended to so suppress responding that resulting
      rate-frequency curves were often invalid. These results suggest a role in MFB
      self-stimulation for only the ventrolateral components of the septo-preoptic
      complex, and support past observations of considerable bilaterality in the neural
      systems that support self-stimulation.

PMID- 17196271
TI  - S-Adenosylmethionine in protozoan parasites: functions, synthesis and regulation.
AB  - S-adenosylmethionine is one of the most frequently used enzymatic substrates in
      all living organisms. It plays a role in all biological methyl transfer reactions
      in as much as it is a donor of propylamine groups in the synthesis of the
      polyamines spermidine and spermine, it participates in the trans-sulphuration
      pathway to cysteine one of the three amino acids involved in glutathione and
      trypanothione synthesis in trypanosomatids and finally it is a source of the 5
      deoxyadenosyl radicals, which are involved in many reductive metabolic processes,
      biodegradative pathways, tRNA modification and DNA repair. This mini-review is an
      update of the progress on the S-adenosylmethionine synthesis in different
      representative protozoan parasites responsible for many of the most devastating
      so-called tropical diseases that have an enormous impact on global health.

PMID- 17196273
TI  - Multiple papillary fibroelastomas of the aortic valve: case report.
AB  - Papillary fibroelastoma is the third most common primary tumor of the heart and
      most commonly involve the cardiac valves. Most papillary fibroelastomas do not
      cause symptoms and they are usually incidental findings by routine
      echocardiography or at autopsy. However, multiple papillary fibroelastomas are
      extremely rare. We report a case with papillary fibroelastoma which was
      incidentally found on echocardiography. Upon surgery, a tumor was found on each
      aortic cusp. Pathological findings of these tumors were consistent with those of
      papillary fibroelastoma.

PMID- 17196272
TI  - Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and
      ventricular remodeling after myocardial infarction.
AB  - We investigated the effect of tissue kallikrein infusion on cardiac protection at
      acute and sub-acute phases after myocardial infarction (MI). Immediately after
      MI, rats were infused with purified tissue kallikrein, with or without icatibant
      (a kinin B2 receptor antagonist). Intramyocardial injection of kallikrein reduced
      myocardial infarct size and inhibited cardiomyocyte apoptosis at 1 day after MI
      associated with increased nitric oxide levels, Akt and glycogen synthase kinase
      3beta phosphorylation and decreased caspase-3 activation. Kallikrein infusion for
      7 days improved cardiac function, normalized left ventricular wall thickness and
      decreased monocyte/macrophage infiltration in the infarct heart. Kallikrein
      treatment reduced NADH oxidase expression and activity, superoxide formation and
      malondialdehyde levels, and reduced MAPK and Ikappa-Balpha phosphorylation, NF
      kappaB activation and MCP-1 and VCAM-1 expression. Kallikrein's effects were all
      blocked by icatibant. These results indicate that kallikrein through kinin B2
      receptor activation prevents apoptosis, inflammation and ventricular remodeling
      by increased nitric oxide formation and suppression of oxidative stress-mediated
      signaling pathways.

PMID- 17196275
TI  - Xuezhikang, an extract of cholestin, decreases plasma inflammatory markers and
      endothelin-1, improve exercise-induced ischemia and subjective feelings in
      patients with cardiac syndrome X.
AB  - Previous studies have demonstrated that Xuezhikang, an extract of cholestin,
      available from Chinese red yeast rice, could effectively modify lipid profile.
      The present study was undertaken to investigate whether Xuezhikang could modify
      endothelin-1 (ET-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein
      (CRP) and exercise-induced ischemia in patients with cardiac syndrome X (CSX).
      Thirty-six patients with CSX were randomly assigned to 1200 mg/d of Xuezhikang or
      placebo group (n=18 respectively). Blood samples were drawn at day 0 and day 90
      for measuring above parameters. The treadmill exercise tests and subjective
      feelings were also assessed at day 0 and day 90. The data showed that Xuezhikang
      therapy resulted in significant reductions in total cholesterol (TC, 19%), low
      density lipoprotein cholesterol (LDL-C) (26%), and triglycerides (TG) compared
      with baseline (16%, p<0.01 respectively). The data also showed that Xuezhikang
      led significantly to reductions in median and log-CRP levels (38% and 44%, p<0.01
      respectively), IL-6 (20%, p<0.01), and ET-1 (47%, p<0.01) compared with baseline.
      The exercise duration, and time to 1 mm ST-segment depression was significantly
      prolonged after Xuezhikang therapy (9% and 6%, p<0.05 respectively) accompanied
      by improvement of subjective feelings. Data suggested that the benefit of
      Xuezhikang resulted in significant modification vascular function by reduction of
      ET-1, inflammatory markers and LDL cholesterol, which may be clinically important
      for patients with CSX.

PMID- 17196274
TI  - Home-based versus hospital-based rehabilitation after myocardial infarction: A
      randomized trial with preference arms--Cornwall Heart Attack Rehabilitation
      Management Study (CHARMS).
AB  - BACKGROUND: Participation in cardiac rehabilitation after acute myocardial
      infarction is sub-optimal. Offering home-based rehabilitation may improve uptake.
      We report the first randomized study of cardiac rehabilitation to include patient
      preference. AIM: To compare the clinical effectiveness of a home-based
      rehabilitation with hospital-based rehabilitation after myocardial infarction and
      to determine whether patient choice affects clinical outcomes. DESIGN: Pragmatic
      randomized controlled trial with patient preference arms. SETTING: Rural South
      West England. METHODS: Patients admitted with uncomplicated myocardial infarction
      were offered hospital-based rehabilitation classes over 8-10 weeks or a self-help
      package of six weeks' duration (the Heart Manual) supported by a nurse. Primary
      outcomes at 9 months were mean depression and anxiety scores on the Hospital
      Anxiety Depression scale, quality of life after myocardial infarction (MacNew)
      score and serum total cholesterol. RESULTS: Of the 230 patients who agreed to
      participate, 104 (45%) consented to randomization and 126 (55%) chose their
      rehabilitation programme. Nine month follow-up data were available for 84/104
      (81%) randomized and 100/126 (79%) preference patients. At follow-up no
      difference was seen in the change in mean depression scores between the
      randomized home and hospital-based groups (mean difference: 0; 95% confidence
      interval, -1.12 to 1.12) nor mean anxiety score (-0.07; -1.42 to 1.28), mean
      global MacNew score (0.14; -0.35 to 0.62) and mean total cholesterol levels (
      0.18; -0.62 to 0.27). Neither were there any significant differences in outcomes
      between the preference groups. CONCLUSIONS: Home-based cardiac rehabilitation
      with the Heart Manual was as effective as hospital-based rehabilitation for
      patients after myocardial infarction. Choosing a rehabilitation programme did not
      significantly affect clinical outcomes.

PMID- 17196276
TI  - Can takotsubo cardiomyopathy be familial?
AB  - Takotsubo cardiomyopathy is a form of reversible left ventricular dysfunction
      that is presumably precipitated by stress. Our observations of the recurrence of
      takotsubo cardiomyopathy in an individual and the occurrence of a reversible
      cardiomyopathy in her daughter lead us to speculate on the possibility of a
      familial predisposition to this entity or its variants.

PMID- 17196278
TI  - Fatness is related to blunted vascular stress responsivity, independent of
      cardiorespiratory fitness in normal and overweight men.
AB  - Obesity is associated with disturbed cardiovascular responsivity to mental
      stress, which may mediate psychosocial disease pathways. Whether being
      aerobically fit is protective against psychophysiological dysfunction in the
      presence of overweight or obesity is undetermined. Peripheral blood flow, blood
      pressure, and cardiac responses were measured during a 2-min mental stress task
      in 48 healthy men (aged 18-32 years). Mental stress-evoked increases in mean
      arterial pressure and heart rate, forearm vasodilatation, and cardiac
      parasympathetic withdrawal. Multiple linear regression analyses adjusted for age,
      peak oxygen uptake, and baseline forearm vascular resistance, revealed that
      greater fatness was related to a blunted vasodilatation response to mental stress
      (beta=-.31, p<.05). There were no interactive effects of fitness and fatness.
      Fitness does not appear to moderate the association between fatness and impaired
      vascular stress responsivity in normal and overweight men.

PMID- 17196279
TI  - A study of the Gamma hypothesis: predictive modelling of the growth and
      inhibition of Enterobacter sakazakii.
AB  - Although the temperature growth profile of the opportunistic pathogen
      Enterobacter sakazakii is known, few other environmental factors affecting growth
      have been analysed. Using a model based on the Gamma hypothesis--that
      antimicrobial factors in mixtures exert independent effects--a range of weak
      acids (lactic, acetic, propionic, citric, sorbic and benzoic), pH, salt and
      temperature and some of their combinations were examined. The weak acids examined
      inhibited principally with the acid-form of the weak acid, however, benzoic,
      sorbic and propionic acids also displayed an inhibitory contribution from their
      respective anionic forms. In all cases pH could be considered an independent
      inhibiting factor. The minimum pH and maximum salt concentration for growth were
      calculated to be 3.89 and 9.1% respectively. In combination, there was no
      suggestion of any interactive effect between them. Studies performed on
      combinations of Na acetate/pH between 25 and 41 degrees C showed that temperature
      did not affect the relative inhibitory effects of the weak acid/pH mixtures. The
      results of this study support the Gamma hypothesis suggesting that there are no
      synergistic interactions between inhibitory factors and that growth can be
      predicted from a library of known effects. More importantly to the food industry,
      the results can be used to design good quality shelf-life challenge tests by
      reducing the number of studies required.

PMID- 17196280
TI  - Enterobacter sakazakii bacteriophages can prevent bacterial growth in
      reconstituted infant formula.
AB  - Reconstituted infant formula has been implicated in outbreaks of Enterobacter
      sakazakii infections, causing high mortality and serious sequelae. Current
      prevention methods appear to be insufficient to ensure that such foods are free
      of E. sakazakii. In this study, the usefulness of bacteriophages for biocontrol
      of E. sakazakii was investigated. Of a total of six new E. sakazakii phages
      isolated from sewage and UV irradiated cultures, two were selected for further
      study by electron microscopy, DNA restriction analysis and SDS-PAGE of structural
      proteins. Purified phages were used to control bacterial growth in broth medium
      and reconstituted infant formula. Both phages effectively prevented development
      of E. sakazakii in formula at various temperatures (12, 24 and 37 degrees C), the
      efficiency of which was dependent upon intrinsic lysis properties and the applied
      phage concentration. We conclude that application of specific bacteriophages may
      provide a means for efficient prevention of E. sakazakii infection through
      reconstituted infant formula.

PMID- 17196281
TI  - Removal of foot-and-mouth disease virus infectivity in salted natural casings by
      minor adaptation of standardized industrial procedures.
AB  - Intestines are used for the production of natural casings as edible sausage
      containers. Derived from animals (pigs and sheep) experimentally infected with
      FMDV (initial dosage 10(7.3) PFU/ml, strain O(1Kaufbeuren)), these natural
      casings were treated with sodium chloride or a phosphate salts/sodium chloride
      mixture and the residual FMDV titres measured. After storage at about 20 degrees
      C, no remaining infectivity was found after either treatment, whereas casings
      stored at 4 degrees C still contained infectivity. Storage of salted casings at
      about 20 degrees C for 30 days is already part of the Standard Operating
      Procedures (included in HACCP) of the international casing industry and can
      therefore be considered as a protective measure for the international trade in
      natural casings.

PMID- 17196282
TI  - Occurrence of ochratoxigenic fungi and ochratoxin A in grapes from a Tunisian
      vineyard.
AB  - The occurrence of ochratoxin A (OTA) and the identification of the ochratoxigenic
      microbiota in Tunisian grapes were studied for the first time. Black aspergilli
      were the dominant genus among the filamentous fungi isolated from grapes and were
      the only potential OTA-producing fungi found. The most abundant species were
      member of Aspergillus niger aggregate (63%) and Aspergillus carbonarius (36%).
      Uniseriate aspergilli were rarely present (1%). Of the A. carbonarius isolates,
      97% were OTA positive but only 3% of the A. niger aggregate isolates were OTA
      positive. During grape maturation, the frequency of black aspergilli increased
      due to increase of the numbers of A. carbonarius. Musts (n=24) obtained from
      grapes collected at the different sampling times were analyzed for their OTA
      content. Up to 37% of the musts contained OTA at levels varying between 0.59 and
      2.57 microg/l. The amounts of OTA in musts increased as grapes matured. These
      results indicate that A. carbonarius is the main cause of OTA contamination of
      Tunisian grapes.

PMID- 17196283
TI  - Ochratoxin A and ochratoxigenic Aspergillus species in Argentinean wine grapes
      cultivated under organic and non-organic systems.
AB  - The evolution of contamination with Aspergillus section Nigri and ochratoxin A
      occurrence was evaluated in four vineyards located at Mendoza province, Argentina
      during 2003-2004. The survey included two grape varieties, one of late maturation
      (Bonarda) and the other of early maturation (Tempranillo). The vineyards were set
      under non-organic and organic cropping systems. Bunches of grapes at different
      growth stages were collected, and berries (50 by sample) were plated on Petri
      dishes containing Dichloran 18% Glycerol Agar (DG18) and Dichloran Rose Bengal
      Chloramphenicol Agar (DRBC) media. After an incubation period of 7 days at 25
      degrees C+/-1 degrees C, the mycoflora belonging to Aspergillus section Nigri was
      identified. The ability to produce ochratoxin A (OTA) by the potential
      ochratoxigenic species was evaluated on YES (2% yeast extract, 15% sucrose)
      medium. The cultures were incubated at 30 degrees C+/-1 degrees C for 10 days in
      darkness. The OTA content of the grapes was determined by HPLC. Through the
      different growth stages, from setting to harvest, grape contamination by the
      Aspergillus species, section Nigri increased. The main species isolated belonged
      to the A. niger aggregate. From 246 strains evaluated 24% was ochratoxigenic. OTA
      was not detected in grapes during the survey.

PMID- 17196284
TI  - Assessment of human enteric viruses in shellfish from the northern Adriatic sea.
AB  - Incidence and circulation of different strains of hepatitis A and Norovirus in
      shellfish were studied on 235 samples (Tapes philippinarum, Mytilus
      galloprovincialis, Ostrea spp. and Chlamys spp.) obtained from different sites,
      representing the shellfish production areas of the northern Adriatic sea.
      Shellfish were harvested in the period of one year and, after depuration, were
      examined for bacterial (Escherichia coli and Salmonella) and viral (HAV and NoV)
      contamination. Viral contamination was present on average in 22% of samples:
      specifically, 6% of samples tested positive for HAV, 14% for NoV and 2% for both
      viruses. None of the samples revealed the presence of Salmonella, and in most of
      them (93%) the number of E. coli was below the European legislation limit of 230
      MPN/100 g. T. philippinarum was the species most often contaminated, as well as
      being the only species in which the legal limit for E. coli was, in some cases,
      exceeded. Both HAV and NoV contamination were detected throughout the year; NoV
      detection was slightly more frequent during winter months, but positive samples
      were also present in summer. The sequencing of the PCR products showed the
      circulation of only one HAV genotype (IA) and four different NoV genotypes
      (Hawaii, Melksham, Lordsdale and GGIIb) with a prevalence of the GGIIb genotype
      in the second period of the monitoring.

PMID- 17196285
TI  - Rational design of novel mutants of fungal 17beta-hydroxysteroid dehydrogenase.
AB  - Reduction of 17-ketosteroids is a biocatalytic process of economic significance
      for the production of steroid drugs. This reaction can be catalyzed by different
      microbial 17beta-hydroxysteroid dehydrogenases (17beta-HSD), like the 17beta-HSD
      activity of Saccharomyces cerevisiae, Pichia faranosa and Mycobacterium sp., and
      by purified 3beta,17beta-HSD from Pseudomonas testosteroni. In addition to the
      bacterial 3beta,17beta-HSD the 17beta-HSD of the filamentous fungus Cochliobolus
      lunatus is the only microbial 17beta-HSD that has been expressed as a recombinant
      protein and fully characterized. On the basis of its modeled 3D structure, we
      selected several positions for the replacement of amino acids by site-directed
      mutagenesis to change substrate specificity, alter coenzyme requirements, and
      improve overall catalytic activity. Replacement of Val161 and Tyr212 in the
      substrate-binding region by Gly and Ala, respectively, increased the initial
      rates for the conversion of androstenedione to testosterone. Replacement of Tyr49
      within the coenzyme binding site by Asp changed the coenzyme specificity of the
      enzyme. This latter mutant can convert the steroids not only in the presence of
      NADP(+) and NADPH, but also in the presence of NADH and NAD(+). The replacement
      of His164, located in the non-flexible part of the 'lid' covering the active
      center resulted in a conformation of the enzyme that possessed a higher catalytic
      activity.

PMID- 17196287
TI  - Engineering primary metabolic pathways of industrial micro-organisms.
AB  - Metabolic engineering is a powerful tool for the optimisation and the
      introduction of new cellular processes. This is mostly done by genetic
      engineering. Since the introduction of this multidisciplinary approach, the
      success stories keep accumulating. The primary metabolism of industrial micro
      organisms has been studied for long time and most biochemical pathways and
      reaction networks have been elucidated. This large pool of biochemical
      information, together with data from proteomics, metabolomics and genomics
      underpins the strategies for design of experiments and choice of targets for
      manipulation by metabolic engineers. These targets are often located in the
      primary metabolic pathways, such as glycolysis, pentose phosphate pathway, the
      TCA cycle and amino acid biosynthesis and mostly at major branch points within
      these pathways. This paper describes approaches taken for metabolic engineering
      of these pathways in bacteria, yeast and filamentous fungi.

PMID- 17196286
TI  - A novel generic dipstick-based technology for rapid and precise detection of
      tetracycline, streptogramin and macrolide antibiotics in food samples.
AB  - Excessive use of antibiotics in veterinary medicine and as growth promoters in
      stock farming has been associated with the dramatically increasing prevalence of
      multidrug-resistant human pathogenic bacteria. European community legislators
      have therefore restricted the veterinary use of antibiotics and banned them as
      growth-promoting food additives in stock breeding (1831/2003/EC). The monitoring
      of such legislation requires technology for precise and straightforward on-site
      quantification of antibiotics in farm samples and food products without the need
      for extensive laboratory equipment and trained personnel. Capitalizing on
      bacterial transcriptional regulators (TetR, PIP, E), which are dose-dependently
      released from their cognate operators (tetO, PIR, ETR) upon binding of specific
      classes of antibiotics (tetracycline, streptogramins, macrolides) we have
      designed an easy-to-handle dipstick-based assay for detection of antibiotic
      levels in serum, meat and milk whose detection limits are up to 40-fold below
      licensed threshold values. The generic dipstick consists of either
      nitrocellulose, nylon or polyvinylidenfluorid (PVDF) membrane strips coated with
      streptavidin and immobilized biotinylated operator DNA, which acts as capture DNA
      to bind hexa-histidine (His(6))-tagged bacterial biosensors. Antibiotics present
      in specific samples triggered the dose-dependent release of the capture DNA
      biosensor interaction, which, after dipping into two different solutions, results
      in a correlated conversion of a chromogenic substrate by a standard His(6)
      targeted enzyme complex. This can be quantified by comparison of the dipstick to
      a standardized color scale or by assessing the terminal solution at 450nm. As
      demonstrated using serum, meat and milk samples spiked with 14 different
      antibiotics, the dipstick technology provided sensitive detection in a rapid
      assay format, and could be employed to monitor non-authorized use of antibiotics
      and to discover novel antibiotics.

PMID- 17196288
TI  - Characterization of the epidemic influenza B viruses isolated during 2004-2005
      season in Taiwan.
AB  - To characterize the antigenic and genetic relationships of influenza B viruses
      isolated during the 2004-2005 season, a total of 11,707 clinical respiratory
      samples were tested of which 1572 (13.5%) were positive for influenza (463 type A
      and 1109 type B influenza). Of the type B viruses, 348 isolates collected in
      different parts of Taiwan were further analyzed. Viruses belonging to both
      influenza B lineages, B/Yamagata/16/88 (B/Yam) and B/Victoris/2/87 (B/Vic) were
      detected, although an increasing number of B/Vic lineage isolates was obtained as
      the season progressed. Recent B/Vic-lineage isolates were found to have
      additional amino acid substitutions compared to isolates from previous seasons,
      indicating that viruses of this lineage continue to evolve significantly and may
      have the capacity to become the dominant influenza B viruses worldwide. Results
      presented in this report demonstrate that antigenically and genetically distinct
      viruses within both B/Vic and B/Yam lineages co-circulate and that reassortment
      among these two lineages occurs frequently contributing to the genetic diversity
      of the circulating strains.

PMID- 17196290
TI  - Delivery of photosensitisers and light through mucus: investigations into the
      potential use of photodynamic therapy for treatment of Pseudomonas aeruginosa
      cystic fibrosis pulmonary infection.
AB  - Respiratory disease is the main cause of morbidity and mortality in patients with
      cystic fibrosis (CF). In such patients chronic Pseudomonas aeruginosa infection
      is virtually impossible to eradicate using antibiotic therapy. Photodynamic
      antimicrobial chemotherapy (PACT) could be one potential alternative
      antimicrobial method. As photosensitisers could be delivered to the lungs of CF
      patients via inhalation, the current in vitro study investigated the potential
      use of PACT in the treatment of P. aeruginosa CF pulmonary infection. Delivery of
      red light (635 nm) and two photosensitisers (toluidine blue O (TBO) and meso
      tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP)) across artificial CF
      mucus was successfully achieved. Artificial CF mucus reduced the measured fluence
      of incident light in an almost exponential manner with increasing depth. The
      presence of dissolved photosensitisers also reduced light fluence. TMP diffused
      more efficiently across artificial CF mucus than TBO. However, receiver
      compartment concentrations of both drugs after 6 h were of the same order as
      those required to achieve high rates of kill (>99%) of P. aeruginosa isolates
      growing both planktonically and in biofilms. TMP required significantly higher
      concentrations (2.5 mg ml(-1)) than TBO to achieve high rates of kill (>99%) of
      P. aeruginosa isolates growing planktonically. Higher concentrations (5.0 mg ml(
      1)) of both photosensitisers were required to achieve high rates of kill (>99%)
      of P. aeruginosa isolates growing in biofilms. When photosensitisers were
      prepared in artificial mucus, higher concentrations were required to achieve
      reasonably high kill rates (>80%) of P. aeruginosa (PAO1) growing both
      planktonically and in biofilm.

PMID- 17196291
TI  - Mechanisms of co-modified liver-targeting liposomes as gene delivery carriers
      based on cellular uptake and antigens inhibition effect.
AB  - In order to deliver antisense oligonucleotides (asODN) into hepatocytes
      orientedly in the treatment of hepatitis B virus (HBV) infection, the liver
      targeting cationic liposomes was developed as a gene carrier, which was co
      modified with the ligand of the asialoglycoprotein receptor (ASGPR), beta
      sitosterol-beta-d-glucoside (sito-G) and the nonionic surfactant, Brij 35. Flow
      cytometry (FCM) analysis and enzyme-linked immunosorbent assay (ELISA) showed
      that the asODN-encapsulating cationic liposomes exhibited high transfection
      efficiency and strong antigens inhibition effect in primary rat hepatocytes and
      HepG2.2.15 cells, respectively. With the help of several inhibitors acting on
      different steps during the targeting lipofection, the cellular uptake mechanisms
      of the co-modified liver-targeting cationic liposomes were investigated through
      antigens inhibition effect assay and confocal laser scanning microscopy (CLSM)
      analysis. The cellular uptake with high transfection efficiency seemed to involve
      both endocytosis and membrane fusion. The ligand sito-G was confirmed to be able
      to enhance ASGPR-mediated endocytosis, the nonionic surfactant Brij 35 seemed to
      be able to facilitate membrane fusion, and the co-modification resulted in the
      most efficient transfection but no enhanced cytotoxicity. These results suggested
      that the co-modified liver-targeting cationic liposomes would be a specific and
      effective carrier to transfer asODN into hepatocytes infected with HBV
      orientedly.

PMID- 17196292
TI  - [Are SPA therapy and pulsed electromagnetic field therapy effective for chronic
      neck pain? Randomised clinical trial. Second part: medicoeconomic approach].
AB  - We report the results of a cost-effectiveness evaluation of pulsed
      electromagnetic field (PEMF) therapy and spa therapy (ST) versus usual care
      (control) for chronic neck pain. MATERIALS AND METHODS: Inclusion criteria were
      age 18 to 80 years with pain in the neck area of more than 3 months' duration and
      no contraindications for PEMF therapy and ST. Randomization to the ST (n=25) and
      PEMF groups (n=26) was blinded, as was collection of data. Non-included subjects
      (n=29) underwent usual care. The trial respected the Helsinki declaration, and
      informed consent was obtained from subjects. The analysis was intent to treat;
      the main outcome measure was increase in health dimension scores on the MOS SF-36
      in terms of increase in French health care costs from 6 months preceding to 6
      months after the start of the study. RESULTS: The increase in health care costs
      was less for the PEMF group (+68 euro+/-539 [95% confidence interval (CI)]: 
      145.0+281) than the ST and control groups. The increase tended to be less, but
      not significantly, for the ST group (+373+/-938 euro [95% CI, -14.0+76.0]) than
      for controls (+618+/-2715 euro [95% CI, -434.0+167.0]). The gain of one physical
      MOS SF-36 unit during one year cost 3400 euro [95% CI, -6759+13 100] for the PEMF
      group, 29,000 euro [95% CI, -1093+59 375] for the ST group and 95076 euro [95%
      CI, -66 769+256 923] for the control group, but the differences were not
      significant. COMMENTARY: These results suggest a potential cost-effectiveness for
      ST and particularly PEMF as compared to usual care in chronic cervical pain. Our
      results perhaps lack significance probably because of lack of statistical power
      and do not distinguish costs related or not to chronic cervical pain.

PMID- 17196289
TI  - The taming of the cell penetrating domain of the HIV Tat: myths and realities.
AB  - Protein transduction with cell penetrating peptides over the past several years
      has been shown to be an effective way of delivering proteins in vitro and now
      several reports have also shown valuable in vivo applications in correcting
      disease states. An impressive bioinspired phenomenon of crossing biological
      barriers came from HIV transactivator Tat protein. Specifically, the protein
      transduction domain of HIV Tat has been shown to be a potent pleiotropic peptide
      in protein delivery. Various approaches such as molecular modeling, arginine
      guanidinium head group structural strategy, multimerization of PTD sequence and
      phage display system have been applied for taming of the PTD. This has resulted
      in identification of PTD variants which are efficient in cell membrane
      penetration and cytoplasmic delivery. In spite of these state of the art
      technologies, the dilemma of low protein transduction efficiency and target
      specific delivery of PTD fusion proteins remains unsolved. Moreover, some
      misconceptions about PTD of Tat in the literature require considerations. We have
      assembled critical information on secretory, plasma membrane penetration and
      transcellular properties of Tat and PTD using molecular analysis and available
      experimental evidences.

PMID- 17196293
TI  - Health-related quality of life in patients with chronic hepatitis C and advanced
      fibrosis.
AB  - BACKGROUND/AIMS: Although the antiviral and histological benefits of
      peginterferon/ribavirin therapy are well established, the effects on health
      related quality of life (HRQOL) and sexual health are less certain. This study
      assessed HRQOL and sexual health in patients with advanced fibrosis or cirrhosis
      in the HALT-C Trial. METHODS: Subjects completed SF-36 and sexual health
      questionnaires prior to and after 24 weeks of peginterferon/ribavirin therapy
      (n=1144). Three hundred and seventy-three (33%) subjects were HCV RNA negative at
      week 20 and continued therapy through week 48; 258 were seen at week 72. One
      hundred and eighty achieved sustained virological responses (SVR) and 78
      relapsed. RESULTS: At baseline, patients had poorer scores for all eight SF-36
      domains compared to healthy controls. Patients with cirrhosis had lower HRQOL
      scores than those with bridging fibrosis, as did patients with higher depression
      scores. SVR patients had significant improvements in seven domains, whereas
      relapsers had significant worsening in one domain. Sexual scores improved in SVR
      patients and decreased in relapsers (p=0.03). In multivariate analyses,
      improvements in HRQOL and sexual scores were significantly associated with SVR
      but were less striking in patients with lower depression scores. CONCLUSIONS:
      Achievement of SVR after peginterferon/ribavirin therapy improves HRQOL and
      sexual health in chronic hepatitis C patients with advanced fibrosis or
      cirrhosis.

PMID- 17196294
TI  - Glycogen storage disease type III-hepatocellular carcinoma a long-term
      complication?
AB  - BACKGROUND/AIMS: Glycogen storage disease III (GSD III) is caused by a deficiency
      of glycogen-debranching enzyme which causes an incomplete glycogenolysis
      resulting in glycogen accumulation with abnormal structure (short outer chains
      resembling limit dextrin) in liver and muscle. Hepatic involvement is considered
      mild, self-limiting and improves with age. With increased survival, a few cases
      of liver cirrhosis and hepatocellular carcinoma (HCC) have been reported.
      METHODS: A systematic review of 45 cases of GSD III at our center (20 months to
      67 years of age) was reviewed for HCC, 2 patients were identified. A literature
      review of HCC in GSD III was performed and findings compared to our patients.
      CONCLUSIONS: GSD III patients are at risk for developing HCC. Cirrhosis was
      present in all cases and appears to be responsible for HCC transformation There
      are no reliable biomarkers to monitor for HCC in GSD III. Systematic evaluation
      of liver disease needs be continued in all patients, despite lack of symptoms.
      Development of guidelines to allow for systematic review and microarray studies
      are needed to better delineate the etiology of the hepatocellular carcinoma in
      patients with GSD III.

PMID- 17196296
TI  - DHLAS: A web-based information system for statistical genetic analysis of HLA
      population data.
AB  - DHLAS (database HLA system) is a user-friendly, web-based information system for
      the analysis of human leukocyte antigens (HLA) data from population studies.
      DHLAS has been developed using JAVA and the R system, it runs on a Java Virtual
      Machine and its user-interface is web-based powered by the servlet engine TOMCAT.
      It utilizes STRUTS, a Model-View-Controller framework and uses several GNU
      packages to perform several of its tasks. The database engine it relies upon for
      fast access is MySQL, but others can be used a well. The system estimates
      metrics, performs statistical testing and produces graphs required for HLA
      population studies: (i) Hardy-Weinberg equilibrium (calculated using both
      asymptotic and exact tests), (ii) genetics distances (Euclidian or Nei), (iii)
      phylogenetic trees using the unweighted pair group method with averages and
      neigbor-joining method, (iv) linkage disequilibrium (pairwise and overall,
      including variance estimations), (v) haplotype frequencies (estimate using the
      expectation-maximization algorithm) and (vi) discriminant analysis. The main
      merit of DHLAS is the incorporation of a database, thus, the data can be stored
      and manipulated along with integrated genetic data analysis procedures. In
      addition, it has an open architecture allowing the inclusion of other functions
      and procedures.

PMID- 17196297
TI  - Pharmaceutical impurities: analytical, toxicological and regulatory perspectives.

PMID- 17196295
TI  - Downregulation of KLF6 is an early event in hepatocarcinogenesis, and stimulates
      proliferation while reducing differentiation.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has the most rapidly rising
      cancer incidence in the US and Europe. The KLF6 tumor suppressor is frequently
      inactivated in HCC by loss-of-heterozygosity (LOH) and/or mutation. METHODS: Here
      we have analyzed 33 HBV- and 40 HCV-related HCCs for mRNA expression of wildtype
      KLF6 (wtKLF6) as well as the KLF6 variant 1 (SV1), a truncated, growth-promoting
      variant that antagonizes wtKLF6 function. The HCV-related tumors analyzed
      represented the full histologic spectrum from cirrhosis and dysplasia to
      metastatic cancer. RESULTS: Expression of KLF6 mRNA is decreased in 73% of HBV
      associated HCCs compared to matched surrounding tissue (ST), with reductions of
      approximately 80% in one-third of the patients. KLF6 mRNA expression is also
      reduced in dysplastic nodules from patients with HCV compared to cirrhotic livers
      (p<0.005), with an additional, marked decrease in the very advanced, metastatic
      stage (p<0.05). An increased ratio of KLF6SV1/wt KLF6 is present in a subset
      (6/33, 18%) of the HBV-related HCCs compared to matched ST. Reconstituting KLF6
      in HepG2 cells by retroviral infection decreased proliferation and related
      markers including cyclin D1 and beta-catenin, increased cellular differentiation
      based on induction of albumin, E-cadherin, and decreased alpha fetoprotein.
      CONCLUSIONS: We conclude that reduced KLF6 expression is common in both HBV- and
      HCV-related HCCs and occurs at critical stages during cancer progression. Effects
      of KLF6 are attributable to regulation of genes controlling hepatocyte growth and
      differentiation.

PMID- 17196298
TI  - Lung cancer screening as a teachable moment for smoking cessation.
AB  - BACKGROUND: Lung cancer screening may serve as a 'teachable moment' for smoking
      cessation, a brief period in which motivation to stop smoking is enhanced. Within
      the context of two NCI-funded randomized lung screening trials, we conducted an
      ancillary study to explore the impact of screening on smoking cessation and
      readiness to stop smoking. METHODS: We accrued a sample of current and former
      smokers participating at the Georgetown University site of the Lung Screening
      Study (LSS; N=144) and of the National Lung Screening Trial (NLST; N=169). In
      each sample, we assessed reasons for trial participation, interest in smoking
      cessation interventions, motivations for stopping smoking, and the impact of
      undergoing screening on tobacco use and readiness to stop smoking. Telephone
      interviews were conducted prior to screening, and 1-month following receipt of
      the screening result. The samples were analyzed separately due to differences in
      age and level of nicotine dependence. RESULTS: The majority of the findings were
      consistent across the two samples. Frequently endorsed reasons for trial
      participation among both current and former smokers included psychological
      reasons (e.g., wanting peace of mind about lung cancer) and altruism (e.g.,
      wanting to make a contribution to science). Nicotine replacement therapy and free
      counseling were the cessation methods that were of most interest, and fear of
      lung health problems was the most frequently endorsed motivation for quitting
      smoking. Regarding readiness to stop smoking, approximately 20% were ready to
      stop in the next 30 days, 45% were ready to stop in the next 6 months, while 35%
      were not thinking of stopping. At the follow-up, 7% of current smokers at
      baseline reported abstinence, and 4% of former smokers at baseline reported
      having relapsed. The findings differed across the two samples when considering
      the readiness to quit outcome. At the 1-month follow-up of the NLST sample,
      participants became more ready to stop smoking (p<.05). Screening result did not
      moderate this finding. In the LSS sample, among younger participants (<or=64), an
      abnormal screening result was significantly associated with becoming more ready
      to stop smoking, whereas a normal result was associated with becoming less ready
      to stop smoking (p=.02). CONCLUSIONS: The current findings demonstrated the
      feasibility of enrolling lung screening participants into a smoking-related
      research study, as well as the high level of interest in stopping smoking and in
      smoking cessation interventions. These data indicate that lung cancer screening
      may serve as a teachable moment for smoking cessation, and suggest that a smoking
      cessation trial within the context of lung cancer screening is feasible.

PMID- 17196299
TI  - Free breathing gated delivery (FBGD) of lung radiation therapy: analysis of
      factors affecting clinical patient throughput.
AB  - PURPOSE: Accurate radiation targeting and delivery within the chest and abdomen
      is greatly affected by the respiratory cycle. Prior methods to minimize
      respiratory effect include breath-hold and abdominal compression techniques;
      these are subject to error secondary to variable inspiration/expiration volumes,
      or by the nature of many cancer patients having inherently poor respiratory
      function. However, advanced technology called free breathing gated delivery
      (FBGD) allows patients to breath normally during treatment. The photon beam is on
      only during a particular prescribed percentage of the respiratory cycle where the
      target tumor volume is minimized. Consequently, by using an intermittent beam,
      the time required to treat a patient is increased. No previous study has
      described the patient throughput ramifications of FBGD. PATIENTS AND METHODS: At
      Emory clinic, a gated treatment delivery system was inaugurated into clinical use
      beginning in June 2004. As of 12/31/2004, 15 patients have completed treatment
      with FBGD. The majority of patients had lung cancer (n=12) with single cases of
      adrenal metastasis, thymoma, and atypical carcinoid. Over 900 gated treatment
      fields (approximately 375 treatment sessions) were reviewed on an IRB-approved
      retrospective protocol. Records from the record-and-verify (R&V) system were
      queried using automated database mining software to obtain the treatment room
      time, treatment field time, beam-on time (BOT), dose rate, and monitor units (MU)
      for each treatment. The presence or absence of a dynamic wedge was also noted, as
      was the prescribed percent of the respiratory cycle treated. For comparison
      purposes, 13 non-gated lung cancer patients (lesions were not moving with
      respiration) were selected from the R&V database. RESULTS: Patients receiving
      FBGD required significantly more time for treatment delivery. The time required
      for FBGD was, on average, 5.5 times greater (range 1.2-12.2) than calculated BOT
      without gating. Time was further increased with the use of a dynamic wedge, which
      occurred in 45% (28/62) of the planned fields. The use of MV imaging also
      increased the time for FBGD treatment sessions by more than 7.5 min on average.
      CONCLUSIONS: FBGD uniformly increases the time required for RT delivery, and MV
      imaging and dynamic wedging even more so. Even though this technology more
      accurately targets tumor volumes while sparing normal tissue, the patient
      throughput issue may deter this technology from being implemented into busy
      clinical practices.

PMID- 17196300
TI  - Influence of clear versus ambiguous normative information on food intake.
AB  - Two studies were conducted in order to examine the conditions under which social
      norms operate to control people's otherwise prepotent response to maximize
      eating. The social-normative model of eating assumes that people will follow one
      of two possible norms for "appropriate" eating behavior: the norm to eat
      minimally and the norm to avoid eating excessively. In Experiment 1, it was
      predicted that amounts eaten would be bimodally distributed (with the modes at or
      just below the two amounts chosen to represent minimal and excessive eating).
      Instead, most participants ate considerably more than either of the norms
      presented. Experiment 2 was intended to test the following explanation for these
      results: exposure to ambiguous norms liberated participants from normative
      constraints and led them to overeat. Experiment 2 demonstrated that exposure to
      clear norms in the same situation exerted a braking effect on overeating. We
      conclude that individuals are more likely to eat in accordance with their own
      desires when they cannot perceive that others are following a clear pattern of
      eating behavior and social norms are, therefore, not apparent.

PMID- 17196301
TI  - Gene therapy in epilepsy: the focus on NPY.
AB  - Gene therapy represents an innovative and promising alternative for the treatment
      of epileptic patients who are resistant to conventional antiepileptic drugs.
      Among the various approaches for the application of gene therapy in the treatment
      of CNS disorders, recombinant viral vectors have been most widely used so far.
      Several gene targets could be used to correct the compromized balance between
      inhibitory and excitatory transmission in epilepsy. Transduction of neuropeptide
      genes such as galanin and neuropeptide Y (NPY) in specific brain areas in
      experimental models of seizures resulted in significant anticonvulsant effects.
      In particular, the long-lasting NPY over-expression obtained in the rat
      hippocampus using intracerebral application of recombinant adeno-associated viral
      (AAV) vectors reduced the generalization of seizures from their site of onset,
      delayed acquisition of fully kindled seizures and afforded neuroprotection. These
      results establish a proof-of-principle for the applicability of AAV-NPY vectors
      for the inhibition of seizures in epilepsy. Additional investigations are
      required to demonstrate a therapeutic role of gene therapy in chronic models of
      seizures and to address in more detail safety concerns and possible side-effects.

PMID- 17196302
TI  - Behavioral profiling of NPY in aggression and neuropsychiatric diseases.
AB  - The abundantly expressed neuropeptide Y (NPY) has potent effects on feeding, body
      weight, and blood pressure, and exhibits important functions in various
      behavioral domains such as motor activity and anxiety. The potent
      neurotransmitter exerts its biological effects through at least five G-protein
      coupled receptors termed Y(1), Y(2), Y(4), Y(5), and y(6). The behavioral profile
      of NPY function has been extensively studied using traditional pharmacological
      and classic genetic animal models. Based on these studies, variations in the
      profile of NPY and its receptors have been found. To limit the variability and
      inconsistencies in the behavioral profile of NPY and to clarify its effects on
      certain domains in further detail, it is important to design a rational
      standardized strategy for behavioral testing, using a complement of different
      well-established and reproducible tests. This strategy can minimize the risk that
      false positive or false negative results lead to a contradictory and inconsistent
      behavioral characterization of NPY function. Ideally, such screening should be
      composed of an initial monitoring of general health, sensory functions, and motor
      abilities, before specific behavioral domains such as anxiety or aggression are
      investigated using a multi-tiered phenotyping approach. In this review, we will
      focus on a brief description of the latest insights into the behavioral profile
      of NPY in the selective lesser investigated domains such as aggression and
      depression-schizophrenia-related behaviors. We will combine this information with
      possible strategies to evaluate the different specific phenotypes in more detail.

PMID- 17196304
TI  - Role of dorsomedial hypothalamic neuropeptide Y in energy homeostasis.
AB  - Hypothalamic neuropeptide Y (NPY) is primarily expressed in the arcuate nucleus
      (Arc) and the dorsomedial hypothalamus (DMH). Although Arc NPY gene expression is
      responsive to circulating leptin, the regulation of DMH NPY expression is leptin
      independent. DMH NPY expression is increased in response to chronic food
      restriction, but not acute food deprivation. DMH NPY expression is elevated in
      pair-fed OLETF rats lacking cholecystokinin (CCK)-1 receptors. A role for CCK in
      controlling DMH NPY expression is demonstrated by the down-regulation of DMH NPY
      by parenchymal DMH CCK administration in intact rats. Moreover, access to running
      wheels normalizes body weight and prevents altered DMH NPY expression of OLETF
      rats. Together, these data suggest that DMH NPY plays an important role in
      feeding and body weight control.

PMID- 17196303
TI  - Possible involvement of endogenous nociceptin/orphanin FQ in the pain-related
      behavioral responses induced by its own metabolite, nociceptin/orphanin FQ(14
      17).
AB  - Nociceptin/orphanin FQ(14-17) (N/OFQ(14-17)) is one of the major fragments that
      are released from N/OFQ, an endogenous ligand for the opioid receptor like-1 (ORL
      1) receptor by endopeptidase 24.11. In the present study, we determined the
      pharmacological profiles of N/OFQ(14-17) on pain-related behavioral responses in
      the mouse. Intrathecal (i.t.) administration of N/OFQ(14-17) (5-160 pmol) evoked
      pain-related behaviors, and these behavioral responses were reduced by i.t. co
      administration of an ORL-1 receptor antagonist, [Nphe(1)]N/OFQ(1-13)NH2 (4 pmol).
      However, in the ligand-binding receptor assay, N/OFQ(14-17) had no affinity for
      the ORL-1 receptor. Furthermore, i.t. pretreatment with an antiserum against
      N/OFQ (1:50) diminished the N/OFQ(14-17)-induced pain-related behaviors,
      suggesting that endogenous N/OFQ is involved in their expression. Therefore,
      N/OFQ(14-17)-induced pain-related behaviors may be mediated through the release
      of endogenous N/OFQ in the mouse spinal cord.

PMID- 17196306
TI  - Amyloid-beta 1-42 induced endocytosis and clusterin/apoJ protein accumulation in
      cultured human astrocytes.
AB  - Recent studies indicate that astrocytes may be the primary target of secreted
      amyloid-beta 1-42 peptides, with the neurotoxicity representing a secondary
      response to astrocytic stress. Our purpose was to clarify the astrocytic stress
      response induced by amyloid-beta peptides in human and rat astrocytes. Human
      amyloid-beta 1-42 peptides and fibrils induced the appearance of cytoplasmic
      vacuoles in normal human astrocytes (NHA) and CCFsttg1 astrocytoma cells.
      Vacuoles appeared 9-12h after the amyloid-beta exposure and remained present for
      several days. Rat primary neonatal astrocytes showed similar but less prominent
      vacuolar response. Human amyloid-beta peptides 1-16, 1-28, 10-20, 17-21 and 25-35
      did not cause vacuole formation. Electron microscopic observations revealed large
      endocytic vacuoles containing fibrillar amyloid material. Stress marker analysis
      did not show any increase in protein levels of HSP70, HSP90, GRP78 and GRP94.
      However, the protein level of clusterin/apoJ, a secreted chaperone, was strongly
      increased both in NHA and CCFsttg1 astrocytes. Endocytic response associated with
      the accumulation of clusterin/apoJ protein suggests that clusterin/apoJ has a
      role in the clearance of amyloid-beta peptides.

PMID- 17196305
TI  - Intraventricular (i3vt) ghrelin increases food intake in fatty Zucker rats.
AB  - Ghrelin is an orexigenic peptide secreted from the stomach and also made in the
      brain. Ghrelin receptors are expressed on hypothalamic cells important in
      appetite and energy balance. We determined that intra-3rd-ventricular (i3vt)
      ghrelin dose-dependently increases acute (1 and 2 h) food intake in lean and
      fatty Zucker rats (0, 0.01, 0.1 and 1.0 nmol ghrelin). The percentage increase of
      food intake in fatty Zucker rats was significantly greater than that in lean
      rats. Fatty Zucker rats had 4.5 times more ghrelin receptor mRNA in the
      hypothalamus than lean Zucker rats, suggesting a possible mechanism for the
      increased sensitivity.

PMID- 17196308
TI  - [Intermittent fever: rare expression of an adenocarcinoma of the ampulla of
      Vater].
AB  - PURPOSE: Prolonged intermittent fevers are frequently seen in internal medicine
      and they constitute a real diagnosis challenge. Infection, auto-immune disease
      and neoplasy are the most common causes. EXEGESIS: We report here a 48 year-old
      man with a prolonged intermittent fever. At first, all his assessments were
      negative and it's only secondary, as clinical and biological disturbances occur
      that the diagnosis of adenocarcinoma of the ampulla has been done. CONCLUSION:
      Neoplasms represent a rare cause of intermittent prolonged fever, but we must
      always keep them in mind. In this case, any specific symptom was initially
      present to end up quickly to the solution.

PMID- 17196307
TI  - Impairment of spatial learning and memory in ELKL Motif Kinase1 (EMK1/MARK2)
      knockout mice.
AB  - The hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer's
      disease (AD) and of the associated cognitive decline. EMK1 (MARK2) is a
      serine/threonine kinase which phosphorylates tau and MAP2. An involvement of this
      kinase in memory functions is not established. We used a behavioral approach to
      study the phenotype of EMK1-null mice (EMK1-KO) as a possible model of MAP2/tau
      altered phophorylation. Compared to wild type mice, EMK1-KO mice did not differ
      in non-cognitive aspects of behavior, such as locomotion in activity cages, or
      anxiety in the elevated plus maze. However, they exhibited lower performance in
      the first stage of acquisition of a hippocampal-dependent spatial learning, as
      assessed in a radial water maze, although, they acquired the task with repeated
      training. They were again found to be impaired on re-learning a new platform
      position. In addition, they exhibited poor long-term retention performance. These
      data underline the importance on both early memory processes and long-term
      retrieval, of the dynamic instability of microtubules generated by the
      phosphorylation of MAPs.

PMID- 17196309
TI  - Radon survey in the high natural radiation region of Niska Banja, Serbia.
AB  - A radon survey has been carried out around the town of Niska Banja (Serbia) in a
      region partly located over travertine formations, showing an enhanced level of
      natural radioactivity. Outdoor and indoor radon concentrations were measured
      seasonally over the whole year, using CR-39 diffusion type radon detectors.
      Outdoor measurements were performed at 56 points distributed over both travertine
      and alluvium sediment formations. Indoor radon concentrations were measured in
      102 living rooms and bedrooms of 65 family houses. In about 50% of all
      measurement sites, radon concentration was measured over each season separately,
      making it possible to estimate seasonal variations, which were then used to
      correct values measured over different periods, and to estimate annual values.
      The average annual indoor radon concentration was estimated at over 1500 Bq/m3
      and at about 650 Bq/m3 in parts of Niska Banja located over travertine and
      alluvium sediment formations, respectively, with maximum values exceeding 6000
      Bq/m3. The average value of outdoor annual radon concentration was 57 Bq/m3, with
      a maximum value of 168 Bq/m3. The high values of indoor and outdoor radon
      concentrations found at Niska Banja make this region a high natural background
      radiation area. Statistical analysis of our data confirms that the level of
      indoor radon concentration depends primarily on the underlying soil and building
      characteristics.

PMID- 17196310
TI  - Persistent oronasal fistula after primary management of facial gunshot injuries.
AB  - We present our experience of treating 42 young men with facial gunshot injuries,
      9 of whom had associated palatal injuries. We attempted definitive treatment at
      the primary operation, but five patients with palatal injuries presented with
      oronasal fistula postoperatively and required secondary intervention. Three
      patients underwent surgical closure using palatal transposition flap, in all of
      whom it was successful.

PMID- 17196311
TI  - Treatment of scaphoid non-unions by a palmar approach with vascularised bone
      graft harvested from the thumb.
AB  - Ten patients with scaphoid non-unions which had been present for longer than 2
      years were treated using a vascularised bone graft harvested from the thumb and
      pedicled on the first dorsal metacarpal artery. Bone harvesting and grafting were
      performed by a single palmar approach. Concomitant cancellous bone graft was not
      used. Bone healing was confirmed by CT scans in nine of the ten patients.
      Persistence of the non-union was observed in one patient who was the oldest in
      this series, had the longest standing non-union and was a heavy smoker. Twelve
      months after surgery, nine of the ten patients had significant pain relief with
      an improved range of motion and grip strength.

PMID- 17196312
TI  - Deciding to resuscitate extremely premature babies: how do parents and
      neonatologists engage in the decision?
AB  - Parents at risk of delivering a baby at the threshold of viability are faced with
      a critical decision. When a child is born between 23 and 25 weeks of gestation,
      parents are asked to decide whether or not to resuscitate their child. In
      essence, they are faced with a choice between life and death. We conducted a
      qualitative study to explore how parents and neonatologists engage in decision
      making in a context of imminent and unplanned delivery at the threshold of
      viability. Twelve parents and attending neonatologists in a specialized tertiary
      care centre in Montreal, Canada were separately interviewed immediately following
      neonatal consultation. Results highlight how neonatologists and parents engage in
      decision making from different standpoints: while neonatologists focus on the
      management of the unborn baby, parents have yet to fully conceptualize their
      infant as a distinct entity since they are in a process of grieving their
      pregnancy and their parenthood project. Moreover, in their attempt to ensure an
      informed decision, neonatologists adopt either of two models through provision of
      the most up-to-date and objective information available: "remaining as neutral as
      possible to allow parents to make their own decision", or, "formulating a
      proposal to which parents can choose or not to assent". Overall, if the provided
      information fits parents' expectations, they tend to feel confident with their
      decision. However, if it does not take their experience into account, their
      decision is experienced as a solitary process. Parents express the need to
      receive more than just factual information from neonatologists. They also require
      support and engagement from caregivers to manage the uncertainty. This brings
      into question the traditional concept of neutral informed consent and suggests
      the necessity of a shared decision-making model to ensure that the decision to
      resuscitate extremely premature babies, at the limits of viability, becomes a
      truly ethical task.

PMID- 17196313
TI  - Is social participation associated with cardiovascular disease risk factors?
AB  - There is increasing interest in the idea that social participation
      (operationalised as taking part in formal groups and associations) is an
      important determinant of health and survival. However, although a large body of
      literature exists which supports the notion that social contact is associated
      with good health, few studies have examined whether participation in specific
      groups and associations is related to specific risk factors, which are in turn
      linked to a major cause of death. In this paper, we focus on risk markers (BMI,
      waist-hip ratio, blood pressure, resting heart rate, anxiety and depression) for
      cardiovascular disease (CVD), which contributes around a third to all cause
      mortality in the UK. Using survey data (n=2334 individuals) from the West of
      Scotland Twenty-07 Study, we examine, separately by sex, cross-sectional
      associations between participation in groups and associations and CVD risk
      markers. There is no consistent patterning in the results. For some types of
      groups, there is a relationship between participation and risk factors in one sex
      but not the other, or better functioning on one health measure but worse in
      another. The most consistent results are found for psychological distress where,
      with the exception of church-related activities, participation in groups and
      associations is related to less distress (although more strongly in men than in
      women). Our findings do not therefore lend unequivocal support to the notion of
      social participation having a strong relationship with CVD risk factors at a
      cross-sectional level.

PMID- 17196314
TI  - Evaluations of community mental health care in low- and middle-income countries:
      a 10-year review of the literature.
AB  - Community-based models of providing mental health services are widely considered
      effective ways of serving individuals diagnosed with mental illness, but more
      comprehensive literature on these models in low- and middle-income countries is
      needed. This study is a systematic review of the effects of community-based
      models on health outcomes of adults with depression, schizophrenia, panic
      disorder, or bipolar disorders in middle- and low-income countries. PubMed,
      PsycINFO, and Cochrane Reviews were searched, returning 500 articles. The
      seventeen interventions included in this review in 14 countries show us that
      community-based mental health services can provide improvements in mental health
      outcomes, and the limited cost analyses suggest cost savings associated with
      community models of care. These findings are in line with much of the research on
      higher income countries. In addition, the studies also point to the gaps in the
      literature on costs, rural areas, bipolar disorders, and panic disorders, and
      note the need for further reviews of interventions targeting additional diseases,
      children, and adolescents as well as studies published in languages other than
      English. This review of the literature serves as a stepping stone for further
      research in community-based mental health services in low- and middle-income
      countries. The works reviewed here provide a base of knowledge that will assist
      us in taking the important next steps in program implementation and evaluation.

PMID- 17196315
TI  - Business cycles, migration and health.
AB  - We investigate the proposition that illness poses as an obstacle to one's ability
      to use migration to hedge the business cycle. We employ data on migration,
      regional unemployment rates and health status from 10 years (1984-1993) of the US
      Panel Study of Income Dynamics. Our results provide considerable for support this
      proposition. The evidence is the strongest for men, but we also find weaker
      evidence for married women. These results suggest that--ceterus paribus-
      aggregate health outcomes in an area should improve when the regional economy
      expands.

PMID- 17196316
TI  - An attenuation of the 'normal' category effect in patients with Alzheimer's
      disease: a review and bootstrap analysis.
AB  - There is a consensus that Alzheimer's disease (AD) impairs semantic information,
      with one of the first markers being anomia i.e. an impaired ability to name
      items. Doubts remain, however, about whether this naming impairment
      differentially affects items from the living and nonliving knowledge domains.
      Most studies have reported an impairment for naming living things (e.g. animals
      or plants), a minority have found an impairment for nonliving things (e.g. tools
      or vehicles), and some have found no category-specific effect. A survey of the
      literature reveals that this lack of agreement may reflect a failure to control
      for intrinsic variables (such as familiarity) and the problems associated with
      ceiling effects in the control data. Investigating picture naming in 32 AD
      patients and 34 elderly controls, we used bootstrap techniques to deal with the
      abnormal distributions in both groups. Our analyses revealed the previously
      reported impairment for naming living things in AD patients and that this
      persisted even when intrinsic variables were covaried; however, covarying control
      performance eliminated the significant category effect. Indeed, the within-group
      comparison of living and nonliving naming revealed a larger effect size for
      controls than patients. We conclude that the category effect in Alzheimer's
      disease is no larger than is expected in the healthy brain and may even represent
      a small diminution of the normal profile.

PMID- 17196317
TI  - Diphenyl ditelluride effect on embryo/fetal development in mice: interspecies
      differences.
AB  - It is well established that diphenyl ditelluride, (PhTe)(2), is a potent
      teratogen in rats, however, little is known about its effects on embryo/fetal
      development in mice. The present study was undertaken to investigate whether any
      differences exist on embryo/fetal development of mice exposed to (PhTe)(2) during
      distinctive periods of gestation compared to rats. Dams were treated
      subcutaneously (s.c.) with 0.12 or 60.0 mg/kg (PhTe)(2) on gestational day (GD)
      4, 8 or 14. Cesarean section was performed on GD18 and external and skeletal
      alterations were examined. The lower dose did not affect any parameter evaluated
      in mouse fetuses. The maternal body weight for 60 mg/kg (PhTe)(2) groups, at all
      periods studied, was not affected. Maternal liver and spleen weights were
      increased at GD8. At GD14, maternal relative weight of kidney was also increased.
      A significant reduction in the number of implantation sites at GD4 was found. At
      GD4 and GD14, there was a reduction in the fetal weight and biometry. A few signs
      of reduced ossification in sternebrae and limbs were observed at GD14 in
      (PhTe)(2) group. In conclusion, (PhTe)(2) was not toxic to dams and affected some
      fetal endpoints only at the dose about 500-fold higher than the dose that was
      teratogenic in rats, suggesting a different developmental toxicity induced by
      (PhTe)(2) among species. Thus, the mice were less susceptible to toxic effects
      induced by (PhTe)(2) than were rats.

PMID- 17196319
TI  - Influence of enamel border and regional variability on durability of resin-dentin
      bonds.
AB  - OBJECTIVES: To evaluate the influence of enamel border on regional resin-dentin
      microtensile bond strength (muTBS) over time. METHODS: Thirty human third molars
      had a flat dentine surface exposed. Two adhesive systems (Single Bond [SB] and
      ScotchBond Multi Purpose Plus [SBMP]) were applied and composite resin crowns
      (Filtek Z250) were constructed. Teeth were divided into three groups (n=5). Group
      A, specimens were sectioned to obtain sticks to be tested in tension (0.5mm/min)
      immediately. Group B specimens were stored without outer enamel in water for 6
      months, before sectioning and testing. Group C, specimens were stored with outer
      enamel in water for 6 months, before sectioning and testing. In all groups, the
      origin of the sticks, periphery and inner regions was controlled. The data for
      each adhesive were subjected to a two-way repeated measure ANOVA (location versus
      storage conditions) and Tukey's test. RESULTS: No significant degradation in
      muTBS was observed for SBMU in all conditions. For SB, a significant reduction on
      muTBS was observed in the specimens without enamel border (group B). The
      degradation was more pronounced in the specimens from the periphery. CONCLUSIONS:
      The three-step etch-and-rinse system is less susceptible to water degradation
      effects; stable resin-dentin bonds can be achieved with two-step etch-and-rinse
      systems as long as there is a bonded enamel border.

PMID- 17196318
TI  - Acetylcholinesterase: converting a vulnerable target to a template for antidotes
      and detection of inhibitor exposure.
AB  - Applications of recombinant DNA technology, chemical synthesis on biological
      templates and fluorescence detection of organophosphorylation provide unexplored
      avenues for development of antidotes and approaches for remote detection of
      organophosphate nerve agents and pesticides. We discuss here how
      acetylcholinesterase (AChE), through appropriate mutations, becomes more
      susceptible to oxime reactivation. Since the reaction between organophosphate and
      the mutated enzyme remains rapid, regeneration of active enzyme by oxime becomes
      the rate-limiting step in the process to complete a catalytic cycle for
      generation of active enzyme. Accordingly, "Oxime-assisted Catalysis" by AChE
      provides a potential means for catalyzing the hydrolysis of organophosphates in
      plasma prior to their reaching the cellular target site. In turn, AChE, when
      conjugated with organophosphate, is employed as a template for 'click-chemistry,
      freeze-frame' synthesis of new nucleophilic reactivating agents that could
      potentially prove useful in AChE reactivation at the target site as well as in
      catalytic scavenging of organophosphates in plasma. Finally, substituted AChE
      molecules can be conjugated to fluorophores giving rise to shifts in emission
      spectra for detection of dispersed organophosphates. Since external reagents do
      not have to be added to detect the fluorescence change, the modified enzyme would
      serve as a remote sensor.

PMID- 17196321
TI  - Uptake of fluoride ions by the glass component of glass ionomer cement.
AB  - OBJECTIVES: The uptake of F(-) ions by glass ionomer cement (GIC) has been
      extensively studied but the precise location of the F(-) ion in the GIC structure
      has not been reported. The aim of this study is to use model materials to
      elucidate the possible locations. GIC consists of residual particles of
      aluminosilicate glass surrounded by depleted glass in an ionically crosslinked
      polymeric matrix. This study evaluates uptake by both unreacted glass particles
      (RAW) and particles acid-treated to produce a depleted glass surface (DEPLETED).
      METHOD: Three glasses, previously studied as cements, were tested at the particle
      size used in GICs. LG30 contained Al, Ca, O, P, and Si; LG26 also contained F and
      AH2 contained Na as well. To produce depleted surfaces they were immersed in
      acetic acid washed and dried at room temperature. Test samples (N=5) were
      immersed in KF solution (900ppm F). Control solutions without glass were used.
      Both were stored at 37C for 48h. F concentrations were measured using ISE with
      TISAB IV. RESULTS: Uptake was Control-test expressed in micromol/g glass. RAW
      LG30=56 (16); LG26=35(17); AH2=17(31). DEPLETED LG30=285(41); LG26=431(42);
      AH2=286(50). The levels of F uptake by DEPLETED were comparable to those found
      with GICs formed with these glasses. CONCLUSIONS: The glass particles of GIC, and
      particularly the depleted zones surrounding them, can account for an appreciable
      amount of the F uptake observed with cements but do not show the same relation
      between F content and F uptake previously observed with cements.

PMID- 17196320
TI  - Effect of compounds of Galla chinensis on remineralisation of initial enamel
      carious lesions in vitro.
AB  - OBJECTIVE: To evaluate the effect of compounds of Galla chinensis on the
      remineralisation of initial enamel carious lesions in vitro. METHODS: Sixty
      bovine enamel blocks with early lesions were prepared and randomly divided into
      six treatment groups. The lesions were subjected to a pH-cycling regime for 12
      days. Each daily cycle included 4x1min applications with one of six treatments;
      1000ppm F aq. (as NaF, positive control); deionized water (negative control); or
      4000ppm aqueous solutions of four G. chinensis extracts (GCEs); GCE, GCE-B, GCE
      B1, or GCE-B2. Surface enamel microhardness was measured on the enamel blocks
      before and after demineralisation, and after pH-cycling, and percentage surface
      microhardness recovery (%SMHR) was calculated. The enamel specimens were then
      sectioned (thickness ca. 80microm) and examined by polarized light microscopy.
      RESULTS: All samples rehardened significantly compared to baseline. Fluoride had
      a significantly greater effect than all other treatments. In the GCEs groups,
      %SMHR was significantly greater than DDW for the GCE, GCE-B and GCE-B1 groups.
      There was no significant difference between the GCE-B2 group and DDW. Polarized
      light microscopy showed that the thickness of the surface layer increased
      obviously in all specimens including NaF group, GCE group, GCE-B group and GCE-B1
      group. Negative birefringent band appeared in the lesions body and the depth of
      the lesions was obviously reduced. CONCLUSION: The present study has demonstrated
      the potential of three GCEs (GCE, GCE-B and GCE-B1) to effect net rehardening of
      artificial carious lesions under dynamic pH-cyclic conditions.

PMID- 17196322
TI  - Cervical diverticulum: an unusual cause of chronic menometrorrhagia.

PMID- 17196323
TI  - Interaction of isopropylthioxanthone with phospholipid liposomes.
AB  - Isopropylthioxanthone (ITX) is a highly lipophilic molecule which can be released
      in foods and beverages from the packages, where it is present as photoinitiator
      of inks in printing processes. Recently it was found in babies milk, and its
      toxicity cannot be excluded. The structure of the molecule suggests a possible
      strong interaction with the lipid moiety of biological membranes, and this is the
      first study of its effects on phospholipid organization, using differential
      scanning calorimetry (DSC) and spin labelling techniques. The data obtained with
      multilamellar liposomes of saturated phospholipids of different length, with and
      without cholesterol, point out that the molecule changes the lipid structure; in
      particular, in the gel state, behaving like a disordering agent it increases the
      mobility of the bilayer, while, in the fluid state, tends to rigidify the
      membrane, in a cholesterol like way. This behavior supports the hypothesis that
      ITX experiences a relocation process when the lipid matrix passes from the gel to
      the fluid state.

PMID- 17196324
TI  - Exploring co-management theory: prospects for sociobiology and reciprocal
      altruism.
AB  - Co-management has gained prominence due to the sustained interest in
      participatory forms of natural resource management. While theoretical development
      posed an initial challenge, it has become an integral part of the co-management
      literature. This paper comprehensively explores co-management theory. It begins
      with an investigation of theory itself. The major elements of theory (concepts,
      variables and relational propositions) are described and a typology of
      theoretical statements (formats) is conceptualized. Co-management theory is
      subsequently charted according to the four schemes (modelling, propositional,
      analytical and meta-theoretical) which make up the typology. Given the maturing
      nature of the co-management literature and the absence of any meta-theoretical
      schemes, we examine the central and underlying assumption of co-operation through
      the science of sociobiology. Reciprocal altruism is pursued to explain why non
      kin co-operate, and is adapted to elucidate the potentials and pitfalls of co
      management. This meta-theory enriches understanding of co-management, provides
      guidance to the other theoretical schemes, and offers a foundational basis upon
      which construction of subtle predications is possible.

PMID- 17196325
TI  - Calcium signalling in astrocytes and modulation of neural activity.
AB  - Starting from the experimental data on ATP evoked calcium responses in
      astrocytes, a biophysical model describing these phenomena was built. The
      simulations showed, in agreement with the experimental findings, that the
      intracellular calcium fluxes mediated by the P2X and P2Y purinoreceptors are
      responsible for the biphasic ATP evoked calcium response in astrocytes. Then, the
      modulation effects on the neural dynamics arising from the release of glutamate
      from astrocyte are also investigated. By using a minimal network model describing
      a neuron coupled to the astrocyte, we demonstrated that the calcium extrusion
      rate through the astrocyte membrane is critically involved in the generation of
      different firing patterns of the neuron.

PMID- 17196327
TI  - T-cell/NK-cell lymphomas: a review.
AB  - T-cell neoplasms are a group of heterogeneous neoplasms that present a challenge
      in management. Accurate diagnosis and classification are necessary for proper
      treatment. This dilemma is exemplified by continuous upgrading of classification
      systems in an effort to better understand these diseases. The spectrum of
      management varies from observation and monitoring to prompt aggressive
      multimodality treatment to achieve optimal outcomes. Allogeneic transplant has
      been successful in a minority of cases with the possibility of cure; however this
      approach is still largely experimental. Molecular studies such as gene expression
      profiling are expected to offer exciting insight into the biology of these
      diseases. Novel therapeutic approaches continue to be explored, however will
      probably require larger clinical trials to establish their utility over the
      current standard.

PMID- 17196326
TI  - Genetically engineered neural stem cells migrate and suppress glioma cell growth
      at distant intracranial sites.
AB  - Our previous study demonstrated successful treatment of an established rat brain
      tumor through the bystander effect by intra-tumoral injection of neural stem
      cells transduced with herpes simplex virus-thymidine kinase gene (NSCtk) followed
      by systemic ganciclovir (GCV) administration (NSCtk therapy). Since glioma has a
      strong tendency to infiltrate into surrounding brain tissue and that is one of
      the main causes of local treatment failure, we, in the present study, injected
      NSCtk cells at distant sites of rat brain tumors and evaluated migratory
      potential of NSCtk toward the tumor and anti-tumor effects of the NSCtk therapy
      of this experimental setting. NSCtk cells were intracranially implanted either at
      2mm medial in the ipsilateral hemisphere or at the mirror point in the
      contralateral hemisphere to the C6 rat glioma cell implantation. Active migration
      of NSCtk cells toward C6 cells was observed even when NSCtk cells were implanted
      in the contralateral hemisphere. When GCV was systemically administered, growth
      of intracranial tumor was markedly inhibited and the survival was significantly
      prolonged through the bystander effect by NSCtk cells migrated from distant
      injection sites of the tumor. The results of the present study suggest that NSCtk
      therapy is still effective in the area far from the NSCtk injection site and,
      therefore, suitable for treatment of malignant gliomas that deeply infiltrate and
      widely disseminate in the brain.

PMID- 17196328
TI  - Removal of nickel ions from water by multi-walled carbon nanotubes.
AB  - Multi-walled carbon nanotubes (MWCNTs) were produced by chemical vapor
      decomposition using acetylene gas in the presence of Ferrocene catalyst at 800
      degrees C, and then oxidized with concentrated nitric acid at 150 degrees C. Both
      (as-produced and oxidized) CNTs were characterized by TEM, Boehm titration, N2
      BET and cation exchange capacity techniques. The adsorption capacity for nickel
      ions from aqueous solutions increased significantly onto the surface of the
      oxidized CNTs compared to that on the as-produced CNTs. The effects of adsorption
      time, solution pH and initial nickel ions concentrations on the adsorption uptake
      of Ni2+ for both the as-produced and oxidized CNTs were investigated at room
      temperature. Both Langmuir and Freundlich isotherm models match the experimental
      data very well. According to the Langmuir model the maximum nickel ions
      adsorption uptake onto the as-produced and oxidized CNTs were determined as
      18.083 and 49.261 mg/g, respectively. Our results showed that CNTs can be used as
      an effective Ni2+ adsorbent due to the high adsorption capacity as well as the
      short adsorption time needed to achieve equilibrium.

PMID- 17196329
TI  - Transport behavior of n-alkane penetrants into castor oil based polyurethane
      polyester nonwoven fabric composites.
AB  - Castor oil based polyurethane (PU)-polyester nonwoven fabric composites were
      fabricated by impregnating the polyester nonwoven fabric in a composition
      containing castor oil and diisocyanate. Composites were fabricated with two
      different isocyanates such as toluene-2,4-diisocyanate (TDI) and hexamethylene
      diisocyanate (HMDI). Transport behavior of n-alkane penetrants (pentane, hexane
      and heptane) into both PUs and PU-polyester nonwoven fabric composites were
      studied. Sorption studies were carried out at different temperatures. From the
      sorption results, the diffusion (D) and permeation (P) coefficients of penetrants
      have been calculated. Significant increase in the diffusion and permeation
      coefficients was observed with increase in the temperature of sorption
      experiments. Drastical reduction in diffusion and permeation coefficients was
      noticed in the composites compared to neat PUs. Attempts were made to estimate
      the empirical parameters like n, which suggests the mode of transport and K is a
      constant depends on the structural characteristics of the composite in addition
      to its interaction with penetrants. The temperature dependence of the transport
      coefficients has been used to estimate the activation energy parameter for
      diffusion (E(D)) and permeation (E(P)) processes from Arrhenius plots.
      Furthermore, the sorption results have been interpreted in terms of the
      thermodynamic parameters such as enthalpy (DeltaH) and entropy (DeltaS).

PMID- 17196330
TI  - Break-up of oil-in-water emulsions by electrochemical techniques.
AB  - Electrochemically-assisted technologies can be successfully applied to the
      treatment of oil-in-water (O/W) emulsions. In this work, it is studied the
      influence of the main parameters (electrical charge passed, pH, electrolyte, oil
      content and operation mode) in the efficiency of these processes, when aluminium
      electrodes are used. The pH was found to be the most significant parameter, and
      good removal efficiencies were only obtained for pHs in the range 5-9. The
      electrical charge passed was observed to be directly related to the aluminium
      supplied to the waste. For a given oil concentration it is required that a
      minimum electrical charge is passed to break-up the emulsion. Further increases
      in the electrical charge lead to increase in the COD removal. The influence of
      the oil concentration is related to that of the electrical charge passed: for a
      given dose of aluminium, the higher the oil content the lower the COD-removal
      efficiency. Likewise, to produce the break-up of the emulsion it is required a
      minimum dose of aluminium (electrical charge passed), lower doses do not attain
      the rupture of the emulsion. The type of electrolyte and its concentration were
      also found to influence the process efficiency. Better efficiencies were obtained
      in the treatment of chloride-containing wastes and for low concentration of
      electrolyte. The destabilization of the O/W emulsion was found to be favoured in
      the discontinuous operation mode. Bridging flocculation is a primary
      destabilization mechanism that can explain the experimental results obtained in
      this work.

PMID- 17196331
TI  - Distribution and cellular localization of high mobility group box protein 1
      (HMGB1) in the spinal cord of a transgenic mouse model of ALS.
AB  - Although the aetiology of amyotrophic lateral sclerosis (ALS) is still elusive,
      increased attention has been put forward on events related to neuroinflammation
      and an active participation of glial cells in the ALS pathogenesis has been
      suggested. However, the specific role of many proinflammatory mediators that
      usually accompany the inflammatory changes is still largely unknown. High
      mobility group box protein 1 (HMGB1) is an ubiquitous nuclear protein that exerts
      numerous extranuclear and extracellular functions, including a proinflammatory
      activity, able to induce cytokines expression and activate inflammatory cells. To
      investigate whether this protein may play a role in the inflammatory events in
      ALS, we examined both expression and localization of HMGB1 in the lumbar spinal
      cord of SOD1G93A transgenic mice, a well established mouse model of familial ALS,
      at different stages of the disease. Intense HMGB1 reactivity was detected in
      ventral horn motor neurons of both non-transgenic and SOD1G93A mice and there was
      no difference in its expression between presymptomatic SOD1G93A mice and
      controls. With the progression of the disease, degenerating neurons showed a
      reduction of HMGB1 immunoreactivity which could reflect an extracellular release
      of this protein. By contrast, in the reactive glial cells HMGB1 was remarkably
      expressed in the nucleus, but not in the cytosol, likely contributing to the
      proliferation and/or hypertrophy of these cells. These results suggest that HMGB1
      may have a different involvement in the motor neurons and glial cells in response
      to the neurotoxic environment in the spinal cord of SOD1G93A mice, and it may
      contribute to the progression of inflammatory and neurodegenerative processes.

PMID- 17196332
TI  - Influence of extremely low frequency magnetic fields on Ca2+ signaling and NMDA
      receptor functions in rat hippocampus.
AB  - Extremely low frequency (ELF<300Hz) electromagnetic fields affect several
      neuronal activities including memory. Because ELF magnetic fields cause altered
      Ca(2+) homeostasis in neural tissues, we examined their influence on Ca(2+)
      signaling enzymes in hippocampus and related them with NMDA receptor functions.
      Hippocampal regions were obtained from brains of 21-day-old rats that were
      exposed for 90 days to 50Hz magnetic fields at 50 and 100 microT intensities. In
      comparison to controls, ELF exposure caused increased intracellular Ca(2+) levels
      concomitant with increased activities of Ca(2+)-dependent protein kinase C (PKC),
      cAMP-dependent protein kinase and calcineurin as well as decreased activity of
      Ca(2+)-calmodulin-dependent protein kinase in hippocampal regions. Simultaneous
      ligand-binding studies revealed decreased binding to N-methyl-D-aspartic acid
      (NMDA) receptors. The combined results suggest that perturbed neuronal functions
      caused by ELF exposure may involve altered Ca(2+) signaling events contributing
      to aberrant NMDA receptor activities.

PMID- 17196333
TI  - Evidence that olfactory sensitivities to calcium and sodium are mediated by
      different mechanisms in the goldfish Carassius auratus.
AB  - The current study investigated whether the olfactory sensitivity to Ca2+ and Na+
      is mediated by the same mechanism in the goldfish, a freshwater teleost. The
      olfactory responses, as assessed by recording the electro-encephalogram (EEG)
      from the olfactory bulb, to changes in external [Ca2+] and to [Na+] were recorded
      in the absence and presence of increasing concentrations of the other ion. Low
      concentrations of Na+ (0-1.0mM) had no significant effects on the olfactory
      response to changes in [Ca2+] in terms of EC50, Imax or Hill co-efficient (n=8).
      A relatively high concentration of Na+ (10mM) significantly reduced the Imax and
      increased the EC50. One hundred millimolars Na+ reduced the olfactory response to
      Ca2+ to undetectable levels. Conversely, low concentrations of Ca2+ (0.1 and
      1.0mM) significantly attenuated the olfactory response to changes in
      environmental [Na+], reducing the amplitude of response and increasing the
      threshold of detection (n=7). However, a high concentration of Ca2+ (10mM) failed
      to attenuate the olfactory response to Na+ completely. Taken together, these
      results suggest that, at normal environmental concentrations of these ions, Ca2+
      and Na+ are detected by distinct and separate cellular mechanisms. However, there
      seems to be a degree of overlap between the two mechanisms. The exact mechanisms
      involved, and their biological roles, remain to be established.

PMID- 17196334
TI  - Activation of leukocyte-endothelial interactions and reduction of selective
      neuronal death after global cerebral ischemia.
AB  - The role of leukocyte-endothelial interactions (LEI) as part of the inflammatory
      response after global cerebral ischemia (GCI) is hardly understood and may be
      detrimental as well as beneficial. Objective of the current study was to
      investigate the cause-effect relationship of activated leukocytes for the
      development of ischemic brain damage. Mongolian gerbils were subjected to 15 min
      of global cerebral ischemia. A cranial window was implanted for quantitative
      analysis of the pial microcirculation focusing on leukocyte-endothelium
      interactions by intravital fluorescence microscopy up to 3 h of reperfusion.
      Subsequently the animals were daily screened for neurological deficits and the
      evolving brain damage was assessed histologically after 4 days. After global
      cerebral ischemia the number of rolling and adherent leukocytes increased 20- and
      >23-fold, respectively upon 3 h of reperfusion as compared to controls (P<0.05).
      Ischemic animals developed neurological deficits and showed a significant loss of
      neurons in selective vulnerable areas of the brain. The extent of leukocyte
      activation, i.e. the maximum number of rollers and stickers directly correlated
      to the number of viable neurons on day 4 in hippocampus, cortex, and striatum. We
      conclude that there is a relationship between activation of leukocyte-endothelium
      interactions and the reduction of ischemic brain damage after global cerebral
      ischemia. Activation of leukocytes may have neuroprotective potential or indicate
      regenerative processes.

PMID- 17196335
TI  - Estradiol prevents the injury-induced decrease of 90 ribosomal S6 kinase (p90RSK)
      and Bad phosphorylation.
AB  - Estradiol prevents neuronal cell death through the activation of cell survival
      signals and the inhibition of apoptotic signals. This study investigated whether
      estradiol modulates the anti-apoptotic signal through the activation of Raf-MEK
      ERK and its downstream targets, including 90 ribosomal S6 kinase (p90RSK) and
      Bad. Adult female rats were ovariectomied and treated with estradiol prior to
      middle cerebral artery occlusion (MCAO). Brains were collected 24h after MCAO and
      infarct volumes were analyzed. We confirmed that estradiol significantly reduces
      infarct volume and decreases the positive cells of TUNEL staining in the cerebral
      cortex. Estradiol prevents the injury-induced decrease of Raf-1, MEK1/2, and
      ERK1/2 phosphorylation. Also, it inhibits the injury-induced decrease of p90RSK
      and Bad phosphorylation. Further, in the presence of estradiol, the interaction
      of phospho-Bad and 14-3-3 increased, compared with that of oil-treated animals.
      Our findings suggest that estradiol prevents cell death due to brain injury and
      that Raf-MEK-ERK cascade activation and its downstream targets, p90RSK, Bad
      phosphorylation by estradiol mediated these protective effects.

PMID- 17196337
TI  - Effects of vasectomy surgery and meloxicam treatment on faecal corticosterone
      levels and behaviour in two strains of laboratory mouse.
AB  - Behaviour was assessed in 32 C57BL/6JCrl and 32 C3H/HeN male mice 1 h following
      vasectomy; saline or meloxicam was administered 30 min prior to surgery at 5, 10,
      or 20 mg kg(-1). Faeces were collected 24 h prior to, and 3, 6, 9, 12, 24 h
      following, vasectomy for measurement of faecal corticosterone. Peak
      corticosterone levels were significantly higher in mice that underwent vasectomy
      and received saline (p<0.001) or meloxicam at 5 or 10 mg kg(-1) (p=0.021, and
      p<0.001, respectively) compared with normal un-operated controls. Mice that
      underwent vasectomy and received 20 mg kg(-1) meloxicam had peak corticosterone
      levels that were not different from normal un-operated mice (p=0.254).
      Discriminant analysis was used to identify behaviours responsible for group
      separation; these were summed to create two behaviour scores. Score 2 (the
      frequency of flinching, writhing, rear leg lift and press 2) was thought to be
      pain related; mice that underwent vasectomy and received saline exhibited
      significantly more of these behaviours than the normal controls (p=0.032), and
      the mice that received meloxicam (at any dose). Strain differences were observed
      in both the stress response to vasectomy and the behavioural changes; the C3H/HeN
      mice had higher pain scores (behaviour Score 2) and peak corticosterone responses
      than the C57BL/6JCrl mice. We have demonstrated that significant changes occur in
      the behaviour of mice following vasectomy, and these changes are reduced by use
      of meloxicam. Vasectomy elicits a rise in corticosterone levels that was only
      reduced by the highest dose of meloxicam.

PMID- 17196338
TI  - Bradykinin-induced nociceptor sensitisation to heat depends on cox-1 and cox-2 in
      isolated rat skin.
AB  - Bradykinin is an important inflammatory mediator that can either activate and/or
      sensitise nociceptors to heat stimuli applied to the skin. Several studies have
      suggested that prostaglandins and thus the cyclooxygenase (cox) enzymes are
      important in the sensitisation process but little is known about the relative
      involvement of the two cox isoforms, cox-1 and cox-2. Extracellular recordings
      were made from C-mechanoheat-sensitive fibres in isolated rat skin-saphenous
      nerve preparations. Bradykinin-mediated sensitisation of heat responses in these
      afferents was significantly attenuated by the selective cox-1 inhibitor, SC-560,
      and by the selective cox-2 inhibitor, NS-398. In the same experiments, bradykinin
      mediated induction of ongoing activity was reduced by SC-560 but not NS-398. In a
      second series of experiments, bradykinin-stimulated synthesis and release of
      prostaglandin E2 (PGE2) was measured in isolated skin-nerve preparations.
      Although the basal release of PGE2 appeared unaffected by either drug, bradykinin
      stimulated PGE2 release from the skin was inhibited by both SC-560 and NS-398.
      Immunocytochemical evaluation revealed cox-1 immunostaining was present in large
      cutaneous nerve branches, small intradermal nerve bundles as well as nerve
      endings within the skin. Cox-1 labelling was also present in non-neuronal cell
      types such as mast cells. Cox-2 immunoreactivity was weak but where present was
      located in small nerve bundles, smaller intradermal nerve bundles and nerve
      endings. This study shows that both cox isoforms are present in skin and that
      they have an important role in mediating bradykinin-evoked heat sensitisation of
      C-MH sensitive fibres through cox-1 and cox-2 dependent prostaglandin synthesis.

PMID- 17196340
TI  - Giant extracellular Glossoscolex paulistus Hemoglobin (HbGp) upon interaction
      with cethyltrimethylammonium chloride (CTAC) and sodium dodecyl sulphate (SDS)
      surfactants: Dissociation of oligomeric structure and autoxidation.
AB  - The effects of two ionic surfactants on the oligomeric structure of the giant
      extracellular hemoglobin of Glossoscolex paulistus (HbGp) in the oxy - form have
      been studied through the use of several spectroscopic techniques such as
      electronic optical absorption, fluorescence emission, light scattering, and
      circular dichroism. The use of anionic sodium dodecyl sulphate (SDS) and cationic
      cethyltrimethyl ammonium chloride (CTAC) has allowed to differentiate the effects
      of opposite headgroup charges on the oligomeric structure dissociation and
      hemoglobin autoxidation. At pH 7.0, both surfactants induce the protein
      dissociation and a significant oxidation. Spectral changes occur at very low CTAC
      concentrations suggesting a significant electrostatic contribution to the protein
      surfactant interaction. At low protein concentration, 0.08 mg/ml, some light
      scattering within a narrow CTAC concentration range occurs due to protein
      surfactant precipitation. Light scattering experiments showed the dissociation of
      the oligomeric structure by SDS and CTAC, and the effect of precipitation induced
      by CTAC. At higher protein concentrations, 3.0 mg/ml, a precipitation was
      observed due to the intense charge neutralization upon formation of ion pair in
      the protein-surfactant precipitate. The spectral changes are spread over a much
      wider SDS concentration range, implying a smaller electrostatic contribution to
      the protein-surfactant interactions. The observed effects are consistent with the
      acid isoelectric point (pI) of this class of hemoglobins, which favors the
      intense interaction of HbGp with the cationic surfactant due to the existence of
      excess acid anionic residues at the protein surface. Protein secondary structure
      changes are significant for CTAC at low concentrations while they occur at
      significantly higher concentrations for SDS. In summary, the cationic surfactant
      seems to interact more strongly with the protein producing more dramatic spectral
      changes as compared to the anionic one. This is opposite as observed for several
      other hemoproteins. The surfactants at low concentrations produce the oligomeric
      dissociation, which facilitates the iron oxidation, an important factor
      modulating further oligomeric protein dissociation.

PMID- 17196339
TI  - PCR identification of Leishmania in diagnosis and control of canine
      Leishmaniasis.
AB  - Leishmaniases are endemic in many countries, mainly in rural areas. In Brazil,
      Leishmania infection is responsible for many cases of Leishmaniases, including
      recent reports in urban regions. Despite their sensitivity, traditional
      serological and parasitological methods for detecting Leishmaniases have proven
      inadequate for species discrimination. This study aimed to identify Leishmania
      species in biological samples by a fast methodology, avoiding "in vitro"
      cultivation. Knowledge of the Leishmania species is an important tool in regions
      where both New World visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL)
      are prevalent. As these new foci appear in areas not traditionally endemic for
      VL, the main problem is to distinguish between true autochthonous infections and
      infections acquired in other well-known endemic areas. Since, domestic dogs are
      known to be the main VL and CL reservoir, they are regularly investigated in
      endemic areas to prevent, principally, severe and often fatal VL in humans.
      However, several infected dogs present no clinical signs or clinical signs
      similar to other canine diseases. Here, we evaluated the ability of PCR to
      diagnose VL and distinguish L. (L.) chagasi from other Leishmania species in
      domestic dogs. Samples from 114 dogs from 30 cities (Sao Paulo, Brazil) were
      divided into two groups: 44 symptomatic and 70 asymptomatic. They were assayed by
      parasitological methods (culture and microscopic examination) and PCR to
      determine L. (L.) chagasi, L. (V.) braziliensis; and in some cases, Leishmania
      spp. Parasitological tests and PCR-L. chagasi were concordant in 105 samples
      (92%). VL was confirmed in 49 dogs, while 56 had negative results. Of the 114
      samples, 9 had discordant results, but were further tested by PCR-Leishmania spp.
      with positive results. VL was also confirmed in 4 dogs having negative
      parasitological tests and positive PCR-L. chagasi. Consequently, this PCR was
      positive for 100% (53/49) of dogs with parasites detected in parasitological
      tests. Also, PCR demonstrated high specificity detecting 61 dogs negative for VL.
      Leishmania infection was negative in 56 dogs, and 5 with positive culture and PCR
      Leishmania spp. had CL since they were positive in PCR-L. braziliensis. This
      study shows the importance of including PCR in diagnosis of Leishmaniases by
      differential diagnosis contributing to the surveillance and control of VL
      programs.

PMID- 17196341
TI  - Echinoderm microtubule-associated protein like protein 4, a member of the
      echinoderm microtubule-associated protein family, stabilizes microtubules.
AB  - Echinoderm microtubule-associated protein (EMAP) is the major microtubule binding
      protein in dividing sea urchin (Strongylocentrotus purpuratus) eggs. Echinoderm
      microtubule-associated protein like protein 4 (Eml4, restrictedly overexpressed
      proliferation-associated protein 120 kDa (Ropp120)) is one of the five mammalian
      EMAP homologues, the cellular function of which remains to be elucidated. In our
      first set of experiments we determined the spatio-temporal expression pattern of
      Eml4 in mouse brain. Our results demonstrate that Eml4 is a highly
      developmentally regulated gene with high expression levels in the developing
      nervous system of E11 embryos declining to low levels in adult. Spatially, Eml4
      expression becomes restricted to the olfactory bulb, hippocampus and cerebellum.
      Transient transfection of a fusion construct of full-length mouse Eml4 with green
      fluorescent protein (GFP-Eml4) into Cos7 and HeLa cells resulted in
      colocalization of GFP-Eml4 with microtubules. This colocalization was observed
      both with microtubules of non-dividing cells and with the mitotic spindle of
      dividing cells. In addition, transient overexpression of GFP-Eml4 in Cos7 cells
      resulted in microtubules that were resistant to nocodazole treatment suggesting
      that Eml4 stabilizes microtubules. A consequence of microtubule stabilization is
      a net reduction in the amount of free tubulin. Microtubule stabilizing proteins
      therefore are expected to indirectly decrease the microtubule growth rate.
      Indeed, transient transfection of GFP-Eml4 resulted in a marked decrease in the
      microtubule growth rate, which is in line with our hypothesis that Eml4 functions
      as a microtubule stabilizing protein. In summary, our results suggest that Eml4
      is a developmentally regulated protein that colocalizes with and stabilizes
      microtubules.

PMID- 17196342
TI  - The prospective preventative HIV vaccine based on modified poliovirus.
AB  - In order to control HIV pandemic, many vaccines are invented. Although none first
      verified its efficacy in clinic, we hypothesize that HIV vaccine based on
      poliovirus is potential to develop the promising one, because it can elicit the
      broad immune response including the main mucosal, humoral and cellular reaction.
      However, the viral neural virulence is one major concern. The attenuated Sabin
      strain is a better candidate. While partial poliovirus genes are replaced by HIV
      antigen genes, the defective interfering particle will fail to produce progeny
      virions, which may further ensure its security. Although the vaccinal immune
      efficacy was verified in some similar animal experiments based on poliovirus to
      express the exogenous genes, more animal and clinical immune trials about HIV
      poliovirus chimeric minireplicons are to be carried out and the hypotheses are to
      be validated.

PMID- 17196343
TI  - Consistency between adolescent reports and adult retrospective reports of
      adolescent marijuana use: explanations of inconsistent reporting among an African
      American population.
AB  - Drug use trends are typically monitored by surveys of retrospective self-reports
      of drug use; yet we know little about the consistency of reports made across the
      life course. This study examines the consistency of marijuana self-reports from
      adolescence and adulthood and what characterizes inconsistent reporting among a
      cohort of African American first graders followed longitudinally from age 6 to 32
      (N=599, 51% female). Self-reported lifetime adolescent marijuana use (ages 16-17)
      and retrospective reports at age 32 were combined to categorize respondents as
      consistent reporters of nonuse (22%), consistent reporters of use (42%), adult
      recanters (19%), adolescent underreporters (8%), and inconsistent reporters of
      age of initiation (9%). Overall, about 64% of the population were consistent in
      their reports of adolescent marijuana use from adolescence to age 32.
      Multivariate logistic regression analyses found that recanters reported less
      marijuana use as adolescents, lower parental supervision during adolescence,
      lower deviant behavior as an adult, and stronger anti-drug values as adults than
      did consistent reporters. Adolescent underreporters reported less assault
      behaviors and less alcohol use as adolescents and had lower first grade math
      achievement than consistent reporters. Family background, depression, criminal
      arrests, and the field conditions of the interview were not related to
      inconsistent reporting.

PMID- 17196344
TI  - Assessment of reproductive parameters in female Dwarf goat (Capra hircus) on the
      basis of progesterone profiles.
AB  - A study was undertaken to look into the reproductive performance of female Dwarf
      goats reared under traditional conditions at NIAB Farm, Faisalabad, Pakistan. The
      serum progesterone profile was used to monitor various reproductive parameters
      (length of postpartum period, resumption of cyclicity, gestation period,
      prepartum period, parturition) in two lots of goats. Litter size, birth weight of
      kids and kidding interval were also observed. Most of the animals conceived
      within 15-59 days of postpartum period. All the does conceived at first or second
      estrus. During gestation period, higher levels of progesterone were maintained
      with wide variations falling in the range of 3-13 ng ml(-1). However, a few days
      before parturition a decline was noticed at 6+/-0.9 days and it reached to the
      basal level of 0.1 ng ml(-1) after the completion of parturition process. The
      length of gestation period was found to be 145.8+/-5 days in the first lot and
      145.2+/-4 days in the second lot. A very short kidding interval (203.7+/-46 days)
      and considerably bigger litter size (1.8+/-0.8) was observed. All the
      parturitions were normal and a considerable weight gain (8.2+/-0.3 kg) of mothers
      was recorded during pregnancy. The initial birth weight of kids was averaged as
      2.1+/-0.5 kg in the first and 1.6+/-0.2 kg in the second lot. It was concluded
      that Dwarf goat has short gestation length, postpartum period and kidding
      interval along with multiple births being common. Due to these factors, its
      reproductive efficiency can be exploited for efficient goat meat production.

PMID- 17196345
TI  - Evidence of increased endometrial vascular permeability at the time of
      implantation in the short-nosed fruit bat, Cyanopterus sphinx.
AB  - Early embryonic development and implantation were studied in tropical short-nosed
      fruit bat Cyanopterus sphinx. We report preimplantation development and embryo
      implantation. Different stages of cleavage were observed in embryo by direct
      microscopic examination of fresh embryos after retrieving them either from the
      oviduct or the uterus at different days, up to the day of implantation.
      Generally, the embryos enter the uterus at the 8-cell stage. Embryonic
      development continued without any delay and blastocyst were formed showing
      attachment to the uterine epithelium at the mesometrial side of the uterus. A
      distinct blue band was formed in the uterus. The site of blastocyst attachment
      was visualized as a blue band following intravenous injection of pontamine blue.
      Implantation occurred 9+/-0.7 days after mating. This study reports that bat
      embryonic development can be studied like other laboratory animals and that this
      bat shows blue dye reaction, indicating the site and exact time of implantation.
      This blue dye reaction can be used to accurately find post-implantational delay.
      We prove conclusively that this species of tropical bat does not have any type of
      embryonic diapause.

PMID- 17196346
TI  - N-Chlorotaurine and ammonium chloride: an antiseptic preparation with strong
      bactericidal activity.
AB  - The bactericidal activity of the endogenous antiseptic N-chlorotaurine (NCT) is
      significantly enhanced in the presence of ammonium chloride which induces the
      formation of monochloramine (NH(2)Cl) whose strong bactericidal activity is well
      known. In this study the properties of NCT plus ammonium chloride have been
      investigated. The reaction of active chlorine compounds like chloramine-T (N
      chlorotoluene-sulfonamide sodium), chloroisocyanuric acid derivatives,
      hypochlorites (NaOCl, CaOCl(2)) with ammonium chloride did not stop at the stage
      of monochloramine, and the pungent smelling by-products di- and trichloramine,
      NHCl(2) and NCl(3), were also formed. This was not the case with NCT where only
      monochloramine was generated. The equilibrium constant of the reaction of NCT
      with ammonium was found to be [Formula: see text] , which allows to estimate the
      equilibrium concentration of monochloramine in aqueous solutions of NCT and
      ammonium chloride. At concentrations each ranging between 0.01% and 1.0% it comes
      to [NH(2)Cl]=3.5-254 ppm. As an unexpected result the monochloramine containing
      formulation turned out to be most stable in plain water without buffer additives.
      Quantitative killing assays revealed complete inactivation of 10(6) to
      10(7)CFU/mL of seven bacterial strains by 0.1% NCT plus 0.1% ammonium chloride
      within 5 min, while with plain 0.1% NCT an incubation time of 2-4h was needed to
      achieve the same effect. The highly significant increase of bactericidal activity
      (200-300-fold) could be assigned to the presence of monochloramine which could be
      isolated by vacuum distillation. Aqueous solutions of NCT and ammonium chloride
      provide a highly effective and well tolerable antiseptic preparation appropriate
      to a treatment cycle of at least 1 month if stored in the refrigerator.

PMID- 17196347
TI  - Differential tumor cell targeting of anti-HER2 (Herceptin) and anti-CD20
      (Mabthera) coupled nanoparticles.
AB  - Two types of antibody-labeled nanoparticles (mAb-NPs) were prepared with the aim
      to achieve specific tumor targeting. Anti-HER2 and anti-CD20 monoclonal
      antibodies (mAb) were used as model ligands. Small poly(dl-lactic acid)
      nanoparticles (PLA NPs) with a mean size of about 170 nm were prepared by the
      salting out method. Thereafter, the coating of PLA NPs with mAbs was performed in
      two steps. First, thiol groups (-SH) were introduced on the surface of PLA-NPs by
      a two-step carbodiimide reaction. The number of -SH groups on the surface of NPs
      increased from 150 to 400 mmol-SH/mol PLA when cystamine concentrations of 25
      1518 mol cystamine/mol PLA were used during the thiolation reaction. In the
      second step, covalent coupling of antibodies to thiolated NPs (NPs-SH) was
      obtained via a bifunctional cross-linker, m-maleimidobenzoyl-N-hydroxy
      sulfosuccinimide ester (sulfo-MBS). For both mAbs anti-HER2 and anti-CD20,
      respectively, the number of -SH functions on the NPs had no influence on the
      amount of mAb coupled to the NPs. Approximately, 295 anti-HER2 and 557 anti-CD20
      molecules, respectively, were covalently coupled per nanoparticle. The NPs size
      after the coupling reactions was about 250 nm. The specific interaction between
      tumor cells and mAb-NPs was determined by confocal microscopy using two cell
      lines: SKOV-3 human ovarian cancer cells (overexpressing HER2) and Daudi lymphoma
      cells (overexpressing CD20). The results showed the selective targeting of mAb
      NPs to tumor cells overexpressing the specific antigen. While anti-CD20 labeled
      NPs (anti-CD20 NPs) bound to and remained at the cellular surface, anti-HER2
      labeled NPs (anti-HER2 NPs) were efficiently internalized. The mAb-NPs represent
      a promising approach to improve the efficacy of NPs in active targeting for
      cancer therapy while the choice of the antibody-target system defines the fate of
      the mAb-NPs after their binding to the cells.

PMID- 17196348
TI  - Effect of WOW process parameters on morphology and burst release of FITC-dextran
      loaded PLGA microspheres.
AB  - Using fluorescein isothiocyanate labeled dextran (FITC-dextran 40, FD40) as a
      hydrophilic model compound, microspheres were prepared by a WOW double emulsion
      technique. Influence of process parameters on microsphere morphology and burst
      release of FD40 from PLGA microspheres was studied. Internal morphology of
      microspheres was investigated by stereological method via cryo-cutting technique
      and scanning electron microscopy (SEM). Drug distribution in microspheres was
      observed with confocal laser scanning microscopy (CLSM). Polymer nature (RG503
      and RG503H) had significant influence on the micro-morphology of microspheres.
      Increase in continuous water phase volume (W2) led to increased surface porosity
      but decreased internal porosity. By increasing PVA concentration in the
      continuous phase from 0.1 to 1%, particle size changed marginally but burst
      release decreased from 12.2 to 5.9%. Internal porosity of microspheres decreased
      considerably with increasing polymer concentration. Increase in homogenization
      speed during the primary emulsion preparation led to decreased internal porosity.
      Burst release decreased with increasing drug loading but increased with drug
      molecular weight. Drug distribution in microspheres depended on preparation
      method. The porosity of microspheres decreased with time in the diffusion stage,
      but internal morphology had no influence on the release behavior in the
      bioerosion stage. In summary, surface porosity and internal morphology play a
      significant role in the release of hydrophilic macromolecules from biodegradable
      microspheres in the initial release phase characterized by pore diffusion.

PMID- 17196349
TI  - Modeling cytoplasmic release of encapsulated oligonucleotides from cationic
      liposomes.
AB  - Transfection activity of antisense oligodeoxynucleotides (ODN)-loaded cationic
      liposomes is mainly restricted by uptake and ODN release into cytoplasm, which is
      difficult to evaluate in cell culture studies. Well-designed models of cellular
      membranes, aim of the present study, might facilitate investigation of such
      processes. In this investigation, a phosphorothioate ODN was actively
      encapsulated in a DODAP-containing cationic liposome by ethanol injection with
      73% efficiency. ODN release was determined by fluorescence dequenching of FITC
      ODN upon incubation of liposomes with early endosomal (EE), late endosomal (LE)
      and plasma membranes (PM) models. LE provided the highest release (up to 76%) in
      a temperature-dependent manner. Release by EE (<16%), total PM (<11%) and PM
      external layer ( approximately 0) were not temperature sensitive. These
      differences are attributed to lipid charge, chain mobility, critical packing
      parameter and cholesterol content of the models. Intracellular distribution of
      FITC-ODN, determined by fluorescence microscopy and flowcytometry in the presence
      and absence of sodium azide, confirmed that liposomes were internalized mainly
      via endocytosis; hence inability of our PL models to simulate such active
      processes. Instead, release of ODN from endosomes into cytoplasm was pH-sensitive
      and in good agreement with model membrane studies in terms of amount and
      mechanism.

PMID- 17196350
TI  - Possible involvement of GABA A-benzodiazepine receptor in the anxiolytic-like
      effect induced by Passiflora actinia extracts in mice.
AB  - Hydroethanol (HE) and methanol (ME) extracts obtained from the leaves of
      Passiflora actinia Hooker were evaluated for behavioral effects in mice. Single
      dose oral administration of HE (300 and 600 mg/kg) or ME (100 and 300 mg/kg)
      resulted in anxiolytic-like effects in the elevated plus-maze. The anxiolytic
      like effects were also seen after the repeated administration of the HE (100 and
      300 mg/kg). Flumazenil (10mg/kg, i.p.), a GABA(A)-benzodiazepine receptor
      antagonist, blocked the effects of ME (300 mg/kg, p.o.) and HE (600 mg/kg). At
      higher doses, a sedative effect produced by acute administration of HE (600
      mg/kg) or ME (300 mg/kg) was indicated by the potentiation of pentobarbital
      induced sleep. With regard to memory-disrupting effects of anxiolytics, mice were
      evaluated by measuring the retest step-down latency 24h after foot-shock in a
      passive avoidance task. In contrast to diazepam (0.5mg/kg) or piracetam
      (200mg/kg), ME (30, 100 and 300 mg/kg) or HE (100, 300 and 600 mg/kg) did not
      influence the step-through latency in the acquisition or retention memory tasks.
      The present results show an anxiolytic profile for HE and ME of Passiflora
      actinia. There are also indications of an involvement of GABA(A) system in this
      effect.

PMID- 17196351
TI  - [A case of papillitis revealing primary syphilis].
AB  - OBJECTIVE: Syphilitic ocular manifestations are polymorphous and usually occur
      during the secondary or tertiary stage of syphilis. We report a case of primary
      syphilis revealed by papillitis. DESIGN: A 22 year old man presented with blurred
      vision in the left eye and decreased visual acuity. Fundus examination and
      fluorescein angiography revealed a papilledema in the left eye and
      chorioretinitis in the right one. Clinical examination revealed a painless
      ulceration of the chin. Blood tests were positive for syphilis (positive reaction
      to the VDRL test and TPHA titer at 1/640) but negative for HIV. After penicillin
      therapy, the ocular manifestations resolved. RESULTS: Papillitis is a relatively
      rare ocular manifestation of syphilis. Our case is original because papillitis
      was the presenting manifestation of the disease and that it was concomitant with
      the primary chancre. CONCLUSION: Systematic screening for syphilis should be
      performed in unexplained ocular inflammation.

PMID- 17196352
TI  - Effects of a progressive loading exercise program on the bone and skeletal muscle
      properties of female osteopenic rats.
AB  - The aim of this study was to determine the effects of a progressive loading
      exercise program on the bone and skeletal muscle properties of female osteopenic
      rats. Forty female Wistar rats (12 weeks old) were divided into four groups
      (n=10): sham-operated sedentary (SS); osteopenic-sedentary (OS); sham-operated
      training (ST) and osteopenic training (OT). Osteopenia was induced by ovariectomy
      (OVX). The exercise program was performed every 48 h for 8 weeks and consisted of
      four bouts of 10 jumps. After 8 weeks, the animals were sacrificed and submitted
      to bone and muscle excision. The tibias were submitted to an evaluation of the
      physical properties and a biomechanical test. The soleus and tibialis anterior
      muscles were weighed and frozen for a cross-sectional area evaluation. Osteopenic
      sedentary animals showed a decrease in bone strength, weight and density. The OT
      group showed higher values for ash weights, bone mineral density and strength, as
      compared to the OS group. The soleus and tibialis anterior muscles of the OT
      group weighed more than those of the osteopenic sedentary and ST groups. Moreover
      the muscle weight showed a significant positive correlation to bone strength. The
      results of this study suggest that the exercise program had a stimulatory effect
      on the bone and muscle tissue of osteopenic rats, leading to the suggestion that
      muscle tissue hypertrophy could have a stimulatory effect on bone mass.

PMID- 17196353
TI  - Preliminary study: color map of hepatocellular carcinoma using dynamic contrast
      enhanced 256-detector row CT.
AB  - To distinguish hepatocellular carcinoma (HCC) from normal liver tissue, a color
      map was made by dynamic contrast-enhanced 256-detector row CT developed at our
      institute. Dynamic enhanced CT of the liver of three patients with HCC was
      studied. The CT has 912 (transverse) x 256 (cranio-caudal) elements, each
      measuring approximately 0.5 mm x 0.5mm at the center of rotation. Scanning for 10
      s (1.0 s/rotation) was started 30 s after intravenous injection of contrast
      medium. The reconstruction increment was 0.62 mm with a time interval of 0.1s and
      a matrix size of 512 x 512 x 256. Color maps were generated to show the gradient
      of the regression line of the time-density change. Due to volume acquisition, the
      3D color map can be created using continuous 10-s scanning. The densities of the
      HCC and liver were decreased and increased during scanning, respectively. The HCC
      was detected clearly in the color map as a downward-sloping region. Dynamic
      enhanced 256-detector row CT could be useful for detecting malignant tumors in
      the liver with a short scan time.

PMID- 17196354
TI  - Ultrasound of the rotator cuff with MRI and anatomic correlation.
AB  - Magnetic resonance imaging and high-resolution ultrasound (US) are frequently
      used for the detection of rotator cuff tears. The diagnostic yield of US is
      influenced by several factors as technique, knowledge of the imaging
      characteristics of anatomic and pathologic findings and of pitfalls. The purpose
      of this article is to illustrates that the standardized high-resolution US
      examination of the shoulder covers the entire rotator cuff and correlates with MR
      imaging and anatomic sections.

PMID- 17196355
TI  - Development and validation of enantioselective high performance liquid
      chromatographic method for Valacyclovir, an antiviral drug in drug substance.
AB  - A chiral high performance liquid chromatographic method was developed and
      validated for the enantiomeric resolution of Valacyclovir, L-valine 2-[(2-amino
      1,6-dihydro-6-oxo-9h-purin-9-yl) methoxy] ethyl ester, an antiviral agent in bulk
      drug substance. The enantiomers of Valacyclovir were resolved on a Chiralpak AD
      (250 mm x 4.6 mm, 10 microm) column using a mobile phase system containing n
      hexane: ethanol: diethylamine (30:70:0.1, v/v/v). The resolution between the
      enantiomers was found not less than four. The presence of diethylamine in the
      mobile phase has played an important role in enhancing chromatographic efficiency
      and resolution between the enantiomers. The developed method was extensively
      validated and proved to be robust. The limit of detection and limit of
      quantification of (D)-enantiomer were found to be 300 and 900 ng/ml,
      respectively, for 20 microL injection volume. The calibration curve showed
      excellent linearity over the concentration range of 900 ng/ml (LOQ) to 6000 ng/ml
      for (D)-enantiomer. The percentage recovery of (D)-enantiomer was ranged from
      97.50 to 102.18 in bulk drug samples of Valacyclovir. Valacyclovir sample
      solution and mobile phase were found to be stable for at least 48 h. The proposed
      method was found to be suitable and accurate for the quantitative determination
      of (D)-enantiomer in bulk drugs substance. It can be also used to test the
      stability samples of Valacyclovir.

PMID- 17196356
TI  - Combined antioxidant effects of rutin and vitamin C in Triton X-100 micelles.
AB  - UV-vis spectra, fluorescence emission spectra and cyclic voltammetric
      measurements were used to study the influence of Vitamin C on the antioxidant of
      rutin in Triton X-100 micelles. Rutin can be located in Triton X-100 micelles
      spontaneously through hydrophobic force, and the binding constant K between rutin
      and Triton X-100 increases with the rutin concentration. The embedment of two
      hydroxyl groups on rutin into the more hydrophobic micellar microenvironment
      makes the oxidation of rutin harder and the radical scavenging activity decrease.
      With low concentration of Vitamin C, the antioxidant capacity of rutin against
      hydroxyl radical is enhanced, while that capacity is partly inhibited when the
      concentration of Vitamin C become higher.

PMID- 17196357
TI  - Micro-algae as a source of protein.
AB  - About five decades ago, the mass production of certain protein-rich micro-algae
      was considered as a possibility to close the predicted so called "protein gap".
      Comprehensive analyses and nutritional studies have demonstrated that these algal
      proteins are of high quality and comparable to conventional vegetable proteins.
      However, due to high production costs as well as technical difficulties to
      incorporate the algal material into palatable food preparations, the propagation
      of algal protein is still in its infancy. To date, the majority of micro-algal
      preparations are marketed as health food, as cosmetics or as animal feed.

PMID- 17196359
TI  - Prospective determinants of smoking cessation in COPD patients within a high
      intensity or a brief counseling intervention.
AB  - OBJECTIVES: The aims of this study were to identify prospective determinants of
      smoking cessation in COPD patients, and to assess whether prospective
      determinants vary between two different cessation interventions. METHODS: Two
      hundred and twenty-five moderate to severe COPD patients were randomly allocated
      to two smoking cessation interventions. One-year cotinine-validated continuous
      abstinence rates were 9% for the minimal intervention strategy for lung patients
      (LMIS) and 19% for the SmokeStopTherapy (SST). The baseline characteristics that
      showed a significant univariate relationship with 1-year continuous abstinence
      (p<.20) were included in the logistic regression model. This procedure was
      performed for each intervention separately. Variables that did not remain
      independent predictors were removed. RESULTS: For the SST separately, no
      independent significant predictor remained. For the LMIS, attitude towards
      smoking cessation (OR: 11.8; 95% CI: 1.7-81.5; p=.013) and cotinine level (OR:
      2.1; 95% CI: 1.08-3.93; p=.028) remained significant predictors. Within the LMIS,
      31% of the variance in continuous abstinence was explained by these variables
      (p=.003). CONCLUSION: This study suggests that a moderately intensive
      intervention (LMIS) is primarily suitable for COPD patients with a positive
      attitude regarding smoking cessation. The more intensive SST can be an
      alternative for patients without such baseline characteristic. PRACTICE
      IMPLICATIONS: This stepped-care approach in smoking cessation counseling may be
      useful in clinical practice and will enable health care providers to match
      interventions to individual needs and increase efficiency.

PMID- 17196358
TI  - The effect of telephone versus print tailoring for mammography adherence.
AB  - OBJECTIVE: The purpose of this intervention was to increase mammography adherence
      in women who had not had a mammogram in the last 15 months. METHODS: A
      prospective randomized intervention trial used four groups: (1) usual care, (2)
      tailored telephone counseling, (3) tailored print, (4) tailored telephone
      counseling and print. Participants included a total of 1244 women from two sites
      a general medicine clinic setting serving predominately low-income clientele and
      a Health Maintenance Organization (HMO). Computer-tailored interventions
      addressed each woman's perceived risk of breast cancer, benefits and/or barriers
      and self-efficacy related to mammography screening comparing delivery by
      telephone and mail. RESULTS: Compared to usual care all intervention groups
      increased mammography adherence significantly (odds ratio 1.60-1.91) when the
      entire sample was included. CONCLUSIONS: All interventions groups demonstrated
      efficacy in increasing mammography adherence as compared to a usual care group.
      When the intervention analysis considered baseline stage, pre contemplators
      (women who did not intend to get a mammogram) did not significantly increase in
      mammography adherence as compared to usual care. PRACTICE IMPLICATIONS: Women who
      are in pre contemplation stage may need a more intensive intervention.

PMID- 17196360
TI  - Gastrointestinal stromal tumours: clinical overview, surgery and recent advances
      in imatinib mesylate therapy.
AB  - AIMS: To review the clinical features of gastrointestinal stromal tumours
      (GISTs), the role of surgery and its principles and molecular targeted therapies.
      METHODS: A Medline-based literature search on relevant topics was performed in
      PubMed for key articles concerning the clinical features, biology and the novel
      strategies in the management, whether surgical and/or pharmaceutical, of
      gastrointestinal stromal tumours. Some information was obtained from Proceedings
      of the American Society for Clinical Oncology published recently. RESULTS:
      Surgical resection, the first-line intervention for operable GISTs, was
      historically the only effective treatment. For residual, metastatic and/or
      inoperable disease, treatment options remain under intense and continuous
      scrutiny. However, their molecular genetics, i.e. the mutations of the genes
      coding for KIT or platelet-derived growth factor receptor alpha, two receptor
      tyrosine kinases, have been targeted for therapeutic intervention by imatinib
      mesylate -- a tyrosine kinase inhibitor. CONCLUSION: Treatment of GISTs with
      imatinib has led to dramatic improvements in progression-free and overall
      survival, thereby rendering its use in the preoperative and postoperative
      treatment under intense investigation. New investigational agents are being
      developed and participation in promising clinical trials remains a standard of
      care.

PMID- 17196361
TI  - Temporary liver blood-outflow occlusion increases effectiveness of radiofrequency
      ablation: an experimental study on pigs.
AB  - AIM: To evaluate the feasibility of liver blood outflow (LBOF) occlusion and its
      impact on the effectiveness of radiofrequency ablation (RFA). METHODS: The
      experiment was performed on 10 pigs. The animals were divided into groups A and B
      according to RFA protocol. In group A (n=5) the RFA time was that taken to reach
      the target temperature of 105 degrees C, whereas group B (n=5) had a constant RFA
      temperature of 105 degrees C and constant time of 8min. The liver blood flow
      (LBF) was quantified using Doppler ultrasonography before LBOF occlusion and
      after that. RFA were performed using an expandable 3cm RF needle. Two liver
      ablations created in different liver lobes were compared; the first ablation was
      created before balloon inflation and the second one was created under LBOF
      occlusion. The time required for RFA procedure, liver ablation volumes, shape and
      microscopic changes of the thermoablated zones were recorded. RESULTS: The LBF
      dropped significantly in all liver vessels after balloon inflation. The volume of
      the ablated area was 8.2+/-2.2cm(3) and increased significantly after LBOF
      occlusion to 17.4+/-3.8cm(3) (p<0.001), in group A. A significant enlargement of
      the ablated area with occluded LBF was registered in group B, it was 6.7+/
      2.8cm(3) versus 19.4+/-1.8cm(3) respectively (p<0.01). CONCLUSIONS: Temporary
      LBOF occlusion led to a significant reduction in liver blood flow, enlargement of
      the thermoablated area volume and homogeneity of the coagulated zones.

PMID- 17196362
TI  - Hepatic arterial Fotemustine chemotherapy in patients with liver metastases from
      cutaneous melanoma is as effective as in ocular melanoma.
AB  - AIM: Hepatic metastases from melanoma are associated with poor prognosis.
      Systemic chemotherapy and biological treatments remain unsatisfactory. This study
      investigated the impact of hepatic arterial chemotherapy in patients with ocular
      and cutaneous melanoma. METHODS: In a retrospectively analysed observational
      study, 36 consecutive patients with hepatic metastases from ocular or cutaneous
      melanoma were assigned for surgical hepatic port-catheter implantation.
      Fotemustine was delivered weekly for a 4-week period, followed by a 5-week rest
      and a maintenance period every 3 weeks until progression. Overall survival,
      response and toxicity were analysed and compared. RESULTS: After port-catheter
      implantation 30/36 patients were finally treated (18 with ocular and 12 with
      cutaneous melanoma). A median of 8 infusions per patient were delivered (range 3
      24). 30% thrombocytopenia grade >or=3, 7% neutropenia grade >or=3 but no nausea
      or vomiting grade >or=3 were encountered. Nine out of 30 patients achieved
      partial remission, 10/30 stable disease; 11/30 patients were progressive. Median
      survival for all treated patients was 14 months. Partial remission and stable
      disease were associated with a survival advantage compared to progressive disease
      (19 vs. 5 months). No significant difference in survival was observed for ocular
      versus cutaneous melanoma. Serum LDH was a significant predictor of both response
      and survival. CONCLUSIONS: Hepatic arterial Fotemustine chemotherapy was well
      tolerated. Meaningful response and survival rates were achieved in ocular as well
      as cutaneous melanoma. Careful patient selection in consideration of extra
      hepatic involvement is crucial for the effectiveness of this treatment.
      Independent from the primary melanoma site, it is debatable if patients with
      highly elevated serum-LDH may benefit from this approach.

PMID- 17196363
TI  - Breast reconstruction following mastectomy for invasive breast cancer by free
      flaps from the abdomen is oncologically safe.
AB  - AIMS: To report the long-term results of oncological safety of breast
      reconstruction by autologous tissue following mastectomy for invasive breast
      cancer. METHODS: One-hundred-fifty-six consecutive patients with invasive breast
      cancer treated with mastectomy and reconstruction by autologous tissue were
      reviewed throughout (from 1987 to 2003 with median follow up time of 66 months).
      RESULTS: Median patient age was 45.9 years (range 26-68). The 157 observed tumors
      had mean diameter of 25+/-19 mm, 70 of them were poorly differentiated, and 137
      were invasive ductal carcinoma. Multifocal disease was present in 44 patients.
      Breast reconstruction was carried out only by autologous tissue (free flaps were
      used in 95% and free TRAM flap transfer was the most common reconstructive
      procedure). There was only one local recurrence as first site of recurrence, thus
      yielding a local recurrence rate of 0.6%. CONCLUSIONS: Breast reconstruction by
      autologous tissue following mastectomy for invasive breast cancer is an
      oncologically safe procedure.

PMID- 17196364
TI  - Reduced glutathione levels and expression of the enzymes of glutathione synthesis
      in cryopreserved hepatocyte monolayer cultures.
AB  - Cryopreservation of monolayers of hepatocytes in a freezing medium containing 10%
      (v/v) dimethylsulfoxide, 90% (v/v) foetal calf serum retains cell morphology and
      viability, but cells lose up to 50% of their intracellular reduced glutathione.
      This is accompanied by a small increase in glutamate cysteine ligase expression
      in cryopreserved cultures, but glutathione synthetase expression is undetectable
      post-cryopreservation. Inclusion of ascorbic acid and alpha-tocopherol in the
      freezing medium improves maintenance of reduced glutathione content post
      cryopreservation at 84% of the levels in non-cryopreserved monolayer cultures,
      but does not restore glutathione synthetase expression. The inability to
      synthesise reduced glutathione will mean that cryopreserved hepatocyte monolayers
      are more susceptible to toxic insults.

PMID- 17196365
TI  - Highly constrained proteins contain an unexpectedly large number of amino acid
      tandem repeats.
AB  - Single-amino-acid tandem repeats are very common in mammalian proteins but their
      function and evolution are still poorly understood. Here we investigate how the
      variability and prevalence of amino acid repeats are related to the evolutionary
      constraints operating on the proteins. We find a significant positive correlation
      between repeat size difference and protein nonsynonymous substitution rate in
      human and mouse orthologous genes. This association is observed for all the
      common amino acid repeat types and indicates that rapid diversification of repeat
      structures, involving both trinucleotide slippage and nucleotide substitutions,
      preferentially occurs in proteins subject to low selective constraints. However,
      strikingly, we also observe a significant negative correlation between the number
      of repeats in a protein and the gene nonsynonymous substitution rate,
      particularly for glutamine, glycine, and alanine repeats. This implies that
      proteins subject to strong selective constraints tend to contain an unexpectedly
      high number of repeats, which tend to be well conserved between the two species.
      This is consistent with a role for selection in the maintenance of a significant
      number of repeats. Analysis of the codon structure of the sequences encoding the
      repeats shows that codon purity is associated with high repeat size interspecific
      variability. Interestingly, polyalanine and polyglutamine repeats associated with
      disease show very distinctive features regarding the degree of repeat
      conservation and the protein sequence selective constraints.

PMID- 17196366
TI  - Chaotic hopping between attractors in neural networks.
AB  - We present a neurobiologically-inspired stochastic cellular automaton whose state
      jumps with time between the attractors corresponding to a series of stored
      patterns. The jumping varies from regular to chaotic as the model parameters are
      modified. The resulting irregular behavior, which mimics the state of attention
      in which a system shows a great adaptability to changing stimulus, is a
      consequence in the model of short-time presynaptic noise which induces synaptic
      depression. We discuss results from both a mean-field analysis and Monte Carlo
      simulations.

PMID- 17196367
TI  - Protein kinase D 3 is localized in vesicular structures and interacts with
      vesicle-associated membrane protein 2.
AB  - Protein kinase D localizes in the Golgi and regulates protein transport from the
      Golgi to the plasma membrane. In the present study, we found that PKD3, a novel
      member of the PKD family, and its fluorescent protein fusions localized in the
      Golgi and in the vesicular structures that are in part marked by endosome
      markers. Fluorescent recovery after photobleaching (FRAP) showed that the PKD3
      associated vesicular structures were constantly forming and dissolving,
      reflecting active subcellular structures. FRAP on plasma membrane-located PKD3
      indicated a slower recovery of PKD3 fluorescent signal compared to those of PKC
      isoforms, implying a different targeting mechanism at the plasma membrane. VAMP2,
      the vesicle-localized v-SNARE, was later identified as a novel binding partner of
      PKD3 through yeast two-hybrid screening. PKD3 directly interacted with VAMP2 in
      vitro and in vivo, and colocalized in part with VAMP2 vesicles in cells. PKD3 did
      not phosphorylate VAMP-GFP and the purified GST-VAMP2 protein in in vitro
      phosphorylation assays. Rather, PKD3 was found to promote the recruitment of
      VAMP2 vesicles to the plasma membrane in response to PMA, while the kinase dead
      PKD3 abolished this effect. Thus, the kinase activity of PKD3 was required for
      PMA-induced plasma membrane trafficking of VAMP2. In summary, our findings
      suggest that PKD3 localizes to vesicular structures that are part of the
      endocytic compartment. The vesicular distribution may be attributed in part to
      the direct interaction between PKD3 and vesicle-associated membrane protein
      VAMP2, through which PKD3 may regulate VAMP2 vesicle trafficking by facilitating
      its recruitment to the target membrane.

PMID- 17196368
TI  - Minimal incision in parotidectomy.
AB  - Conservative parotidectomy has been for years an effective and well-established
      technique. Recently, aesthetic considerations have been reviewed. A minimal pre-
      and retroauricular incision is proposed that does not extend to the hair-bearing
      skin. This reduces the length of the scar and the extent of the dissection
      improving aesthetic results. This is a retrospective study of 32 parotidectomies
      performed through this incision because of benign parotid diseases and diagnosed
      by fine needle aspiration cytology. The minimal incision is mainly indicated in
      small and medium-sized tumours located in the superficial lobe of the parotid
      gland. Neither operating time nor the morbidity associated with parotidectomy is
      increased with this safe and effective technique for the treatment of benign
      parotid masses.

PMID- 17196369
TI  - Effects on growth after switching protease inhibitors to efavirenz in HIV-1
      infected children.

PMID- 17196370
TI  - Characterisation of in vitro-selected mutants of Ureaplasma parvum resistant to
      macrolides and related antibiotics.
AB  - Resistant mutants of Ureaplasma parvum were selected by serial passages of a
      susceptible strain in subinhibitory concentrations of different macrolides and
      related antibiotics (erythromycin, azithromycin, josamycin, quinupristin,
      quinupristin/dalfopristin, pristinamycin and telithromycin). Mechanisms of
      resistance were characterised by sequencing portions of genes encoding 23S rRNA
      and ribosomal proteins L4 and L22. Mutants with significantly increased minimum
      inhibitory concentrations could be selected with all the selector antibiotics,
      except quinupristin and pristinamycin. Mutants harboured mutations in domain V of
      the 23S rRNA gene at nucleotides G2056, G2057 or A2058 (Escherichia coli
      numbering) and in conserved portions of ribosomal proteins L4 and L22. Most of
      the mutations were associated with complete loss of macrolide and ketolide
      activity, whereas streptogramin combinations were less affected.

PMID- 17196371
TI  - Characterisation of KLUA-9, a beta-lactamase from extended-spectrum cephalosporin
      susceptible Kluyvera ascorbata, and genetic organisation of bla(KLUA-9).
AB  - This study characterised the genetic environment of the chromosomally encoded
      bla(KLUA-9) gene from a clinical Kluyvera ascorbata isolate and performed a
      kinetic characterisation of KLUA-9. Purified KLUA-9 showed the highest catalytic
      efficacies towards benzylpenicillin, ampicillin, piperacillin, first-generation
      cephalosporins, cefuroxime and cefoperazone; like other 'cefotaximases', it
      showed a much higher rate of hydrolysis of cefotaxime than ceftazidime, whilst
      dicloxacillin, cefoxitin and imipenem behaved as poor substrates. A 9kb insert
      from K. ascorbata was cloned (Escherichia coli KK68C1) and sequenced. bla(KLUA-9)
      and its 266bp upstream flanking region (almost identical to the integron
      associated bla(CTX-M-2)) are preceded by an aspat variant, a ypdABC-like operon
      and two open reading frames with unknown functions. Unlike ISCR1-associated
      bla(CTX-M-2) genes, we failed to detect the putative orf513 recombination sites.
      Instead, we were able to localise the 5bp target sites for insertion of ISEcp1B,
      suggesting that this element could be responsible for future (or still
      undetected) mobilisation of bla(KLUA-9) to more efficiently transferred elements.

PMID- 17196372
TI  - Activities of four frog skin-derived antimicrobial peptides (temporin-1DRa,
      temporin-1Va and the melittin-related peptides AR-23 and RV-23) against anaerobic
      bacteria.
AB  - The activities of two antimicrobial peptides belonging to the temporin family
      (temporin-1DRa from Rana draytonii and temporin-1Va from Rana virgatipes) and two
      peptides with structural similarity to the bee venom peptide melittin (AR-23 from
      Rana tagoi and RV-23 from R. draytonii) were evaluated against a range of
      reference strains and clinical isolates of anaerobic bacteria. These peptides
      were selected because they show broad-spectrum growth inhibitory activity against
      reference strains of several medically important aerobic microorganisms and
      against clinical isolates of methicillin-resistant Staphylococcus aureus. All
      peptides showed relatively high potency (minimum inhibitory concentration (MIC)
      </=25 microM) against the Gram-positive bacilli Propionibacterium acnes and
      Clostridium tertium and the Gram-positive cocci Peptostreptococcus anaerobius.
      Activity was lower and more variable against Clostridium septicum, Clostridium
      perfringens and Peptostreptococcus asaccharolyticus. Growth of the Gram-negative
      bacilli Bacteroides fragilis and Fusobacterium spp. was poorly inhibited, but all
      the peptides were active (MIC</=25 microM) against Prevotella melaninogenica. The
      clinical utility of the melittin-related peptides is limited by their toxicities,
      but temporin-1DRa and temporin-1Va have relatively low haemolytic activity
      against human erythrocytes and so represent candidates for drug development,
      particularly for topical therapy of infected surface lesions.

PMID- 17196373
TI  - Long-lasting behavioral effects of juvenile trauma in an animal model of PTSD
      associated with a failure of the autonomic nervous system to recover.
AB  - BACKGROUND: Early life exposure to potentially traumatic experiences (PTEs)
      significantly increases the risk of responding more severely to stressful events
      experienced in adulthood. The aim of this study was to assess the autonomic
      nervous system (ANS) response to exposure to two PTEs in youth and again in
      adulthood, in terms of heart rate and heart rate variability in animals that
      responded to the PTE dramatically as compared to those that displayed virtually
      no behavioral response and to control animals. METHODS: The prevalence of
      individuals displaying extreme anxiety-like behavioral responses to the PTE
      (predator urine or elevated platform) was assessed in the elevated plus-maze and
      startle response paradigms. Behavioral paradigms were complemented by assessment
      of the involvement of the ANS in relation to changes in behavior. RESULTS:
      Juvenile trauma increases the vulnerability for developing long-term behavioral
      disruptions, taken to represent post-traumatic stress symptoms, after a second
      exposure to the same stressor in adulthood. PTSD-like behaviors and persisting
      physiological abnormalities resulted from disturbed recovery from the initial
      stress response. CONCLUSIONS: Exposure to a PTE during youth can have significant
      and long-lasting effects in adulthood and predispose the individual to PTSD upon
      subsequent re-exposure. Monitoring of ANS parameters confirms that development of
      extreme long-term (PTSD-like) behavioral changes is associated with a failure of
      recovery from the initial ANS responses to stress exposure.

PMID- 17196374
TI  - Effect of GABAergic ligands on the anxiolytic-like activity of DOI (a 5-HT(2A/2C)
      agonist) in the four-plate test in mice.
AB  - 5-HTergic and GABAergic systems are involved in neurobiology of anxiety.
      Precedent studies have demonstrated that SSRIs possessed an anxiolytic-like
      effect in the four-plate test (FPT) at doses that did not modify spontaneous
      locomotor activity. This effect seems to be mediated through the activation of 5
      HT(2A) postsynaptic receptors. The purpose of the present study was to examine
      the implication of GABA system in the anxiolytic-like activity of DOI in the FPT.
      To achieve this, the co-administration of DOI (5-HT(2A/2C) receptor agonists)
      with GABA(A) and GABA(B) receptor ligands was evaluated in the FPT. Alprazolam,
      diazepam and muscimol (for higher dose) potentiated the anxiolytic-like effect of
      DOI. Bicuculline, picrotoxin and baclofen inhibited the anxiolytic-like effect of
      DOI. Flumazenil and CGP 35348 had no effect on the anxiolytic-like activity of
      DOI. These results suggest that the GABA system seems to be strongly implicated
      in the anxiolytic-like activity of DOI in the FPT.

PMID- 17196375
TI  - The nature of the cell cycle in neurons: focus on a "non-canonical" pathway of
      DNA replication causally related to death.
AB  - The mechanism whereby a reactivation of cell cycle in neurons causes cell death
      is beginning to be identified. In cellular models of Alzheimer's disease,
      activation of a non-canonical pathway of DNA replication contributes to neuronal
      death. This pathway involves the repair enzyme DNA polymerase-beta, which is
      highly expressed in neurons of the Alzheimer's brain at early stages of the
      disease. Loading of DNA polymerase-beta into the replication forks generates a
      death signal, which involves the tumor suppressor p53. The increasing knowledge
      of the main actors of the unscheduled DNA replication in neurons will pave the
      way for novel therapeutic interventions in Alzheimer's disease and other
      neurodegenerative disorders.

PMID- 17196376
TI  - Effect of laser modified surface microtopochemistry on endothelial cell growth.
AB  - The introduction of microelectronics technology in the area of biological
      sciences has brought forth previously unforeseeable applications such as DNA or
      protein biochips, miniaturized, multiparametric biosensors for high performance
      multianalyte assays, DNA sequencing, biocomputers, and substrates for controlled
      cell growth (i.e. tissue engineering). We developed and investigated a new method
      using "cold" excimer laser beam technology combined with microlithographical
      techniques to create surfaces with well defined 3D microdomains in order to
      delineate critical microscopic surface features governing cell-material
      interactions. Microfabricated surfaces with microgrooves 30-3 microm deep, 10 - 1
      microm wide spaced 30 microm apart were obtained with micron resolution, by
      "microsculpturing" polymer model surfaces using a computer controlled laser KrF
      excimer beam coupled with a microlithographic projection technique. The laser
      beam after exiting a mask was focused onto the polymer target surface via an
      optical setup allowing for a 10-fold reduction of the mask pattern. Various 3D
      micropatterned features were obtained at the micron level. Reproducible submicron
      features could also be obtained using this method. Subsequently, model human
      umbilical endothelial cells (HUVEC) were cultured on the laser microfabricated
      surfaces in order to study the effects of specific microscopic surface features
      on cell deposition and orientation. Cell deposition patterns were found to be
      microstructure dependant, and showed cell orientation dependency for features in
      the cell range dimension, a behaviour significantly different from that of a
      previously studied cell model (osteoprogenitor cell). This model may be a
      promising in so far as it is very rapid (a time frame less than a second per
      square centimeter of micropatterned surface) and provides further insights into
      the effects of surface microtopography on cell response with possible
      applications in the field of biosensors, biomedical and/or pharmaceutical
      engineering sciences.

PMID- 17196378
TI  - Current issues relating to drug safety especially with regard to the use of
      biomarkers: a meeting report and progress update.
AB  - An expert group met in Leiden to review the state-of-the-art in detecting drug
      related safety problems and to review the role of biomarkers and modelling
      techniques. It was clear that new drugs are not necessarily safer than old drugs,
      despite much larger clinical trial programs. Larger or longer clinical trials may
      be unfeasible and postmarketing surveillance is not being undertaken
      systematically enough to ensure safety. Biomarkers could improve drug safety by
      detecting drug-related signals early but determining whether the biomarker is on
      the causal pathway to toxicity is difficult. The maturity and utility of safety
      related biomarkers varies among target organ systems. A consortium approach to
      assimilate a large amount of biomarker-related safety signals incorporating this
      information into mechanism-based models may provide a useful way forward. However
      no techniques will ensure that drugs are perfectly safe and communication with
      the public is required to achieve mutual understanding of benefit risk/balance
      assessments.

PMID- 17196377
TI  - Changes of some anti-oxidative physiological indices under soil water deficits
      among 10 wheat (Triticum aestivum L.) genotypes at tillering stage.
AB  - Drought is one of the major ecological factors limiting crop production and food
      quality globally, especially in the arid and semi-arid areas of the world. Wheat
      is the staple food for more than 35% of world population and wheat cultivation is
      mainly restricted to such zones with scarcity of water, so wheat anti-drought
      physiology study is of importance to wheat production, food safety and quality
      and biotechnological breeding for the sake of coping with abiotic and biotic
      conditions. The current study is to investigate changes of anti-oxidative
      physiological indices of 10 wheat genotypes at tillering stage. The main results
      and conclusion of tillering stage in terms of activities of POD, SOD, CAT and MDA
      content as followed: (1) 10 wheat genotypes can be generally grouped into three
      kinds (A-C, respectively) according to their changing trend of the measured
      indices; (2) A group performed better drought resistance under the condition of
      treatment level 1 (appropriate level), whose activities of anti-oxidative enzymes
      (POD, SOD, CAT) were higher and MDA lower; (3) B group exhibited stronger anti
      drought under treatment level 2 (light-stress level), whose activities of anti
      oxidative enzymes were higher and MDA lower; (4) C group expressed anti-drought
      to some extent under treatment level 3 (serious-stress), whose activities of anti
      oxidative enzymes were stronger, MDA lower; (5) these results demonstrated that
      different wheat genotypes have different physiological mechanisms to adapt
      themselves to changing drought stress, whose molecular basis is discrete gene
      expression profiling (transcriptom). The study in this respect is the key to
      wheat anti-drought and biological-saving water in worldwide arid and semi-arid
      areas; (6) POD, SOD, and CAT activities and MDA content of different wheat
      genotypes had quite different changing trend at different stages and under
      different soil water stress conditions, which was linked with their origin of
      cultivation and individual soil water threshold, which will provide better
      reference to selecting proper plant species for eco-environmental construction
      and crops for sustainable agriculture in arid and semi-arid areas.

PMID- 17196379
TI  - Application of NMR-based metabonomics in the investigation of myocardial ischemia
      reperfusion, ischemic preconditioning and antioxidant intervention in rabbits.
AB  - NMR based metabonomics was applied in rabbit plasma samples during myocardial
      ischemia-reperfusion injury, with the following interventions: (1) Control (no
      intervention); (2) ischemic preconditioning (IpC); (3) administration of
      melatonin; (4) IpC+administration of melatonin; (5) treatment of the indole
      derivative C6458. The (1)H NMR signal intensity ratio of lactate/glucose was
      found to increase in Control samples during reperfusion compared to baseline,
      while lactate+alanine/acetate was decreased suggesting impairment of aerobic
      glycolysis and concomitant lipid utilization. In contrast, after IpC or treatment
      with C6458, the lactate/glucose ratio was similar to baseline in accordance with
      the previously reported decrease in infarct size. Multivariate statistical
      methods such as Principal Component Analysis (PCA), and Discriminant Analysis
      (DA) were used for the discrimination of samples. The use of ANOVA variable
      preselection prior to PCA was advantageous in producing adequate models. PCA
      could classify the Control group in three clusters according to the condition of
      the heart (baseline-ischemia-reperfusion) while in the IpC groups no
      classification was evident. PCA discrimination upon treatment with melatonin and
      C6458 provided further evidence of their effect on the metabolic profile. The
      supervised DA resulted in fine discrimination between the different subgroups.
      Plasma NMR spectra in combination with pattern recognition techniques proved to
      be an efficient and simple method to depict the metabolic changes produced upon
      ischemia-reperfusion of the myocardium.

PMID- 17196380
TI  - [Canavan disease or N-acetyl aspartic aciduria: a case report].
AB  - Canavan disease or N-acetyl aspartic aciduria, is an autosomal recessive
      leukodystrophy characterized by spongy degeneration of brain. The disease is an
      inborn error of metabolism caused by aspartoacylase deficiency resulting from
      accumulation of N-acetyl aspartic acid in the brain. The authors report a case in
      a 10-month-old boy who presented with developmental delay and megalencephaly
      noticeable after 4 months of age. Magnetic resonance imaging of the brain showed
      diffuse white matter degeneration. The diagnosis of Canavan disease was confirmed
      by nuclear magnetic resonance spectroscopy and gas chromatography-mass
      spectrometry.

PMID- 17196383
TI  - Performance of anaerobic thermophilic fluidized bed in the treatment of cutting
      oil wastewater.
AB  - This paper examines the effect of organic loading rate on the removal efficiency
      of COD and TOC anaerobic thermophilic fluidized bed reactor (AFBR) in the
      treatment of cutting-oil wastewater at different hydraulic retention time (HRT)
      conditions. The essays are development at laboratory scale using a porous support
      medium. The AFBR reactor was subjected to a programme of steady-state operation
      over a range of hydraulic retention times, HRTs, in the range 12-2h and organic
      loading rates, OLRs, between 11.9 and 51.3kgCOD/m(3)d. The highest efficiency was
      95.9% for an OLR of 13kgCOD/m(3)d and HRT of 11h. Over an operating period of 92
      days, an OLR of 51.3kgCOD/m(3)d was achieved with 67.1% COD removal efficiency
      (71.3% TOC) in the experimental AFBR reactor. Although the level of biogas
      generation was not high, the anaerobic fluidized bed technology provided
      significant advantages over the conventional physico-chemical treatment applied
      in the factory. The effluent had a better quality (lower organic loading) and it
      was possible to reuse it in different applications in the factory (e.g.,
      irrigation of gardens). The biological treatment did not lead to the generation
      of oily sludge, which is considered as hazardous waste by legislation.
      Furthermore, a continuous stream is produced and this reduced the impact of large
      flows discharged 4-5 times per week to the urban collector and MWWTP (municipal
      wastewater treatment plant).

PMID- 17196382
TI  - Synergistic effects of cinnamaldehyde in combination with eugenol against wood
      decay fungi.
AB  - The combined effects of using cinnamaldehyde with catechin, quercetin or eugenol
      against wood decay fungi were examined by comparing their isoeffective
      concentrations to that of individual compound. Among all combinations,
      cinnamaldehyde with eugenol revealed the strongest synergy against Laetiporus
      sulphureus. The synergism was due to the interference of fungal cell wall
      synthesis and cell wall destruction plus radical scavenging effect. Results also
      suggested that antioxidant with fungicidal effect might be a better candidate
      than pure antioxidant for the system of fungicide/antioxidant.

PMID- 17196384
TI  - Synthesis, structural revision, and antioxidant activities of antimutagenic
      homoisoflavonoids from Hoffmanosseggia intricata.
AB  - Intricatinol and intricatin, the two homoisoflavonoids isolated from
      Hoffmanosseggia intricata, and two analogs have been synthesized from pyrogallol
      in three steps. The spectral data of synthetic intricatinol are in good agreement
      with those of natural metabolite, but the spectral data of intricatin are not
      corroborative with those of the natural product. The structure of intricatin has
      been thus revised to 8-methoxybonducellin, a compound isolated from Caesalpinia
      pulcherrima. The antioxidant activity of all the four homoisoflavonoids was
      determined by superoxide (NBT) and DPPH free radical scavenging methods. The
      synthetic analog 7,8-dihydroxy-3-[(3,4-dihydroxyphenyl)methylene]chroman-4-one
      displayed excellent activity in both methods.

PMID- 17196386
TI  - N-Alkyl-N-alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of carboxylic acid
      containing drugs.
AB  - Synthesis and hydrolysis in aqueous buffers of novel N-alkyl-N
      alkyloxycarbonylaminomethyl (NANAOCAM) and N-aryl-N-alkyloxycarbonylaminomethyl
      (NArNAOCAM) derivatives of carboxylic acid containing drugs were carried out. The
      hydrolysis follows a S(N)1 type mechanism and is dependent on the nucleofugacity
      of the leaving group. Topical delivery of the NANAOCAM derivative of naproxen
      from IPM across hairless mice skin was examined in in vitro diffusion cell
      experiments. The prodrug was 4.5-fold less lipid soluble, 2.4-fold less water
      soluble and 3.6-fold less permeable than the parent drug.

PMID- 17196385
TI  - Discovery of novel, non-acidic 1,5-biaryl pyrrole EP1 receptor antagonists.
AB  - Replacement of the carboxylic acid group in a series of previously described 1,5
      biaryl pyrrole EP1 receptor antagonists led to the discovery of various novel non
      acidic antagonists. Several analogues displayed high binding affinity and high
      binding efficiency indices.

PMID- 17196387
TI  - Synthesis and biological evaluation of fenobam analogs as mGlu5 receptor
      antagonists.
AB  - Optimization of affinity and microsomal stability led to identification of the
      potent, metabolically stable fenobam analog 4l. Robust in vivo efficacy of 4l was
      demonstrated in four different models of anxiety. Additionally, a ligand based
      pharmacophore alignment of fenobam and MPEP is proposed.

PMID- 17196388
TI  - Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired
      antifungal resistance and trailing growth in Candida albicans.
AB  - Among fungal pathogens such as Candida albicans, acquired drug resistance has not
      been associated with plasmids or other transferable elements, but it is thought
      to involve primarily mutations and genetic or epigenetic phenomena. This prompted
      us to test some histone deacetylase inhibitors (HDACi) from our library, in
      combination with fluconazole, against C. albicans strains in vitro. Among the
      tested compounds, the two chloro-containing uracil-hydroxamates 1c and 1d showed
      a strong reduction of the MIC values on Candida strains that show the trailing
      growth effect. In this assay, 1c,d were more potent than SAHA, a well-known HDAC
      inhibitor, in reducing the Candida growth. More interestingly, 1c,d as well as
      SAHA were able to inhibit the fluconazole-induced resistance induction in Candida
      cultures.

PMID- 17196389
TI  - Synthesis, characterization, antibacterial activity, and interaction with DNA of
      the vanadyl-enrofloxacin complex.
AB  - The neutral mononuclear vanadyl complex with the quinolone antibacterial drug
      enrofloxacin has been prepared and characterized with physicochemical and
      spectroscopic techniques and molecular mechanics calculations. The interaction of
      the complex with calf-thymus DNA has also been investigated and the antimicrobial
      activity has been evaluated against three different microorganisms.

PMID- 17196390
TI  - Structure-activity relationships of 3-aminoquinazolinediones, a new class of
      bacterial type-2 topoisomerase (DNA gyrase and topo IV) inhibitors.
AB  - A series of 3-aminoquinazolinediones was synthesized and evaluated for its
      antibacterial and DNA gyrase activity. The SAR around the quinazolinedione core
      was explored and the optimal substitutions were combined to give two compounds,
      2r and 2s, with exceptional enzyme potency (IC50 = 0.2 microM) and activity
      against gram-positive organisms (MIC's = 0.015-0.06 microg/mL).

PMID- 17196391
TI  - HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self
      renewal, and tumorigenicity.
AB  - Cancer stem cells are rare tumor cells characterized by their ability to self
      renew and to induce tumorigenesis. They are present in gliomas and may be
      responsible for the lethality of these incurable brain tumors. In the most
      aggressive and invasive type, glioblastoma multiforme (GBM), an average of about
      one year spans the period between detection and death [1]. The resistence of
      gliomas to current therapies may be related to the existence of cancer stem cells
      [2-6]. We find that human gliomas display a stemness signature and demonstrate
      that HEDGEHOG (HH)-GLI signaling regulates the expression of stemness genes in
      and the self-renewal of CD133(+) glioma cancer stem cells. HH-GLI signaling is
      also required for sustained glioma growth and survival. It displays additive and
      synergistic effects with temozolomide (TMZ), the current chemotherapeutic agent
      of choice. TMZ, however, does not block glioma stem cell self-renewal. Finally,
      interference of HH-GLI signaling with cyclopamine or through lentiviral-mediated
      silencing demonstrates that the tumorigenicity of human gliomas in mice requires
      an active pathway. Our results reveal the essential role of HH-GLI signaling in
      controlling the behavior of human glioma cancer stem cells and offer new
      therapeutic possibilities.

PMID- 17196392
TI  - Structural and mechanistic insights into the action of Plasmodium falciparum
      spermidine synthase.
AB  - Spermidine synthase is currently considered as a promising drug target in the
      malaria parasite, Plasmodium falciparum, due to the vital role of spermidine in
      the activation of the eukaryotic translation initiation factor (eIF5A) and cell
      proliferation. However, very limited information was available regarding the
      structure and mechanism of action of the protein at the start of this study.
      Structural and mechanistic insights of the P. falciparum spermidine synthase
      (PfSpdSyn) were obtained utilizing molecular dynamics simulations of a homology
      model based on the crystal structures of the Arabidopsis thaliana and Thermotoga
      maritima homologues. Our data are supported by in vitro site-directed mutagenesis
      of essential residues as well as by a crystal structure of the protein that
      became available recently. We provide, for the first time, dynamic evidence for
      the mechanism of the aminopropyltransferase action of PfSpdSyn. This
      characterization of the structural and mechanistic properties of the PfSpdSyn as
      well as the elucidation of the active site residues involved in substrate,
      product, and inhibitor interactions paves the way toward inhibitor selection or
      design of parasite-specific inhibitors.

PMID- 17196393
TI  - Aortic valve-sparing repair with autologous pericardial leaflet extension has a
      greater early re-operation rate in congenital versus acquired valve disease.
AB  - OBJECTIVE: We sought to establish whether there was a difference in outcome after
      aortic valve repair with autologous pericardial leaflet extension in acquired
      versus congenital valvular disease. METHODS: One hundred and twenty-eight
      patients underwent reparative aortic valve surgery at our institution from 1997
      through 2005 for acquired or congenital aortic valve disease. The acquired group
      (43/128) (34%) had a mean age of 56.4+/-20.3 years (range, 7.8-84.6 years) and
      the congenital group (85/128) (66%) had a mean age of 16.9+/-19.2 years (range,
      0.3-82 years). The endpoints of the study were mortality and reoperation rates.
      RESULTS: Thirty-day mortality was 0/43 (0%) in the congenital group and 1/85
      (1.1%) in the acquired group. Late mortality in the acquired group was 3/43 (7%)
      and 3/84 (3.5%) in the congenital group (neither early nor late proportion of
      mortality is significantly different between the two groups, according to the
      nonparametric Binomial test for proportions). There were 13 total reoperations
      among 11 patients: 1/43 (2.3%) in the acquired group and 10/85 (11.7%) in the
      congenital group (p=0.07). Two patients from the congenital group were reoperated
      on twice. The mean interval between original repair and reoperation was 3.6+/-5
      years (range, 0-7 years) for acquired and 3.5+/-2.5 years (range, 0-7 years) for
      the congenital group (Wilcoxon 2-sample test, p=0.7). Total early reoperation
      rate (<30 days after first surgery) was 11/128 (8.5%); for the congenital group
      9/85 (10.5%) and for the acquired group 2/43 (4.6%). Early reoperation rate was
      significantly higher among the congenital group (p=0.013). The remaining patients
      are well at mean follow-up of 2.8+/-2.4 years (range 0-7.9). In the acquired
      group, the mean postoperative aortic regurgitation and stenosis grade by
      echocardiography was 0.5+/-0.3 (scale, 0-4) and 0.3+/-0.1, respectively. In the
      congenital group, the follow-up, mean aortic regurgitation and stenosis were
      0.9+/-0.8 and 0.5+/-0.3, respectively. CONCLUSIONS: There was no significant
      difference in early or late mortality and late reoperation rate between the two
      groups. Early reoperation rate was higher in the congenital versus the acquired
      aortic valvular disease group. This study supports the fact that the valve
      sparing technique is safe and reproducible and repeatable in patients with
      acquired valve disease.

PMID- 17196394
TI  - Human oligodendrocytes derived from embryonic stem cells: Effect of noggin on
      phenotypic differentiation in vitro and on myelination in vivo.
AB  - In attempts to produce mature oligodendrocytes from human embryonic stem (huES)
      cells, we searched conditions inducing transcription factors Olig1/2, as well as
      Nkx2.2 and Sox10, which are needed for maturation. This was obtained by retinoic
      acid treatment followed by noggin, an antagonist of bone morphogenetic proteins
      (BMPs). We found that retinoic acid induces BMPs in huES cells. Addition of
      noggin at a specific step was essential to form numerous mature oligodendrocytes
      with ramified branches and producing myelin basic protein (MBP). We describe a
      procedure converting huES cells into enriched populations of oligodendrocyte
      precursors that can be expanded and passaged repeatedly and subsequently
      differentiated into mature cells. Transplantation of such precursors showed that
      pretreatment by noggin markedly stimulates their capacity to myelinate in the
      brain of MBP-deficient shiverer mice in organotypic cultures and in living
      animals. Arrays of numerous long MBP+ fibers were generated over extended areas
      in the brain, with evidence of cell migration after transplantation and with
      formation of compact myelin sheaths.

PMID- 17196396
TI  - The role of the biceps brachii in shoulder elevation.
AB  - The biceps brachii is a bi-articular muscle affecting motion at the shoulder and
      elbow. While its' action at the elbow is well documented, its role in shoulder
      elevation is less clear. Therefore, the purpose of this project was to
      investigate the influence of shoulder and elbow joint angles on the shoulder
      elevation function of the biceps brachii. Twelve males and 18 females were tested
      on a Biodex dynamometer with the biceps brachii muscle selectively stimulated at
      a standardized level of voltage. The results indicated that both shoulder and
      elbow joint angles influence the shoulder joint elevation moment produced by the
      biceps brachii. Further analysis revealed that the elevation moment was greatest
      with the shoulder joint at 0 degrees and the elbow flexed 30 degrees or less. The
      greatest reduction in the elevation moment occurred between shoulder angles of 0
      degrees and 30 degrees . The shoulder elevation moment was near zero when
      shoulder elevation reached or exceeded 60 degrees regardless of elbow angle.
      These results clarify the role of the biceps in shoulder elevation, as a dynamic
      stabilizer, and suggest that it is a decelerator of the arm during the throwing
      motion.

PMID- 17196395
TI  - Functional refolding of a recombinant C-type lectin-like domain containing
      intramolecular disulfide bonds.
AB  - The lectin-like oxidized low-density lipoprotein scavenger receptor (LOX-1) is a
      pro-inflammatory marker and Type II membrane protein expressed on vascular cells
      and tissues. The LOX-1 extracellular domain mediates recognition of oxidized low
      density lipoprotein (oxLDL) particles that are implicated in the development of
      atherosclerotic plaques. To study the molecular basis for LOX-1-mediated ligand
      recognition, we have expressed, purified and refolded a recombinant LOX-1 protein
      and assayed for its biological activity using a novel fluorescence-based assay to
      monitor binding to lipid particles. Overexpression of a hexahistidine-tagged
      cysteine-rich LOX-1 extracellular domain in bacteria leads to the formation of
      aggregates that accumulated in bacterial inclusion bodies. The hexahistidine
      tagged LOX-1 molecule was purified by affinity chromatography from solubilized
      inclusion bodies. A sequential dialysis procedure was used to refold the purified
      but inactive and denatured LOX-1 protein into a functionally active form that
      mediated recognition of oxLDL particles. This approach allowed slow LOX-1
      refolding and assembly of correct intrachain disulfide bonds. Circular dichroism
      analysis of the refolded LOX-1 molecule demonstrated a folded state with
      substantial alpha-helical content. Using immobilized recombinant, refolded LOX-1
      we demonstrated a 70-fold preferential recognition for oxLDL over native LDL
      particles. Thus, a protein domain containing intrachain disulfide bonds can be
      reconstituted into a functionally active state using a relatively simple dialysis
      based technique.

PMID- 17196397
TI  - No difference between conscious and nonconscious visuomotor control: evidence
      from perceptual learning in the masked prime task.
AB  - Negative compatibility effects (NCEs) in the masked-prime paradigm are usually
      obtained when primes are masked effectively. With ineffective masks-and primes
      above the perceptual threshold-positive compatibility effects (PCEs) occur. We
      investigated whether this pattern reflects a causal relationship between
      conscious awareness and low-level motor control, or whether it reflects the fact
      that both are affected in the same way by changes in physical stimulus
      attributes. In a 5-session perceptual learning task, participants learned to
      consciously identify masked primes. However, they showed unaltered NCEs that were
      not different from those produced by participants in a control group without
      equivalent perceptual learning. A control experiment demonstrated that no NCEs
      occur when prime identification is made possible by ineffective masking. The
      results suggest that perceptual awareness and low-level motor control are
      affected by the same factors, but are fundamentally independent of each other.

PMID- 17196398
TI  - Spatial dynamics of masked picture repetition effects.
AB  - The aim of this study was to further elucidate the mechanisms of early and
      automatic object processing using a masked picture priming paradigm with both
      identity and exemplar repetition in functional MRI (fMRI). Masked repetition
      priming has been commonly used with words to isolate automatic, rapidly occurring
      mechanisms involved in visual word recognition; however, studies using the
      technique of masked priming with rapid presentation of pictures have been
      limited. This study demonstrates how the masked priming technique can be used to
      study early, automatic processing of rapidly presented complex objects. Temporal
      occipital regions previously found to be sensitive to repetition priming in both
      masked word and unmasked picture studies were found to show repetition
      suppression for the identity primes only. Most notably, when divided into
      anterior and posterior divisions, the fusiform gyrus showed anatomically specific
      repetition suppression only in the posterior portion. This finding is comparable
      to that found in a previous study of masked word priming, and the similarity may
      suggest an overlap in the early identification processes for visual word form and
      visual object processing in this region. Finally, masked repetition of different
      exemplar objects did not result in reliable neural effects, suggesting that the
      underlying mechanisms of the more semantic-based, different exemplar priming may
      occur later or require the intervention of conscious processes.

PMID- 17196399
TI  - EEG dynamics of the frontoparietal network during reaching preparation in humans.
AB  - Visuomotor transformation processes are essential when accurate reaching
      movements towards a visual target have to be performed. In contrast, those
      transformations are not needed for similar, but non-visually guided, arm
      movements. According to previous studies, these transformations are carried out
      by neuronal populations located in the parietal and frontal cortical areas (the
      so-called "dorsal visual stream"). However, it is still debated whether these
      processes are mediated by the sequential and/or parallel activation of the
      frontoparietal areas. To investigate this issue, we designed a task where the
      same visual cue could represent either the target of a reaching/pointing movement
      or the go-signal for a similar but non-targeting arm movement. By subtracting the
      event-related potentials (ERPs) recorded from healthy subjects performing the two
      conditions, we identified the brain processes underlying the visuomotor
      transformations needed for accurate reaching/pointing movements. We then
      localized the generators by means of cortical current density (CCD)
      reconstruction and studied their dynamics from visual cue presentation to
      movement onset. The results showed simultaneous activation of the parietal and
      frontal areas from 140 to 260 ms. The results are interpreted as neural
      correlates of two critical phases of visuomotor integration, namely target
      selection and movement selection. Our findings suggest that the visuomotor
      transformation processes required for correct reaching/pointing movements do not
      rely on a purely sequential activation of the frontoparietal areas, but mainly on
      a parallel information processing system, where feedback circuits play an
      important role before movement onset.

PMID- 17196400
TI  - A semi-parametric approach to estimate the family-wise error rate in fMRI using
      resting-state data.
AB  - One of the most important considerations in any hypothesis based fMRI data
      analysis is to choose the appropriate threshold to construct the activation maps,
      which is usually based on p-values. However, in fMRI data, there are three
      factors which necessitate severe corrections in the process of estimating the p
      values. First, the fMRI time series at an individual voxel has strong temporal
      autocorrelation which needs to be estimated to obtain the corrected parametric p
      value. The second factor is the multiple comparisons problem arising from
      simultaneously testing tens of thousands of voxels for activation. A common way
      in the statistical literature to account for multiple testing is to consider the
      family-wise error rate (FWE) which is related to the distribution of the maximum
      observed value over all voxels. The third problem, which is not mentioned
      frequently in the context of adjusting the p-value, is the effect of inherent low
      frequency processes present even in resting-state data that may introduce a large
      number of false positives without proper adjustment. In this article, a novel and
      efficient semi-parametric method, using resampling of normalized spacings of
      order statistics, is introduced to address all the three problems mentioned
      above. The new method makes very few assumptions and demands minimal
      computational effort, unlike other existing resampling methods in fMRI.
      Furthermore, it will be demonstrated that the correction for temporal
      autocorrelation is not critical in implementing the proposed method. Results
      using the proposed method are compared with SPM2.

PMID- 17196401
TI  - Rosales sister to Fabales: towards resolving the rosid puzzle.

PMID- 17196402
TI  - Increased ghrelin levels in epileptic patients.

PMID- 17196403
TI  - A selective cyclooxygenase-2 inhibitor decreases transforming growth factor-beta1
      synthesis and matrix production in human peritoneal mesothelial cells.
AB  - High glucose concentration, which provides the chief driving force in peritoneal
      dialysis, has been considered to be an important initial factor that contributes
      to peritoneal thickening and fibrosis. Human peritoneal mesothelial cells (HPMCs)
      and the expansion of extracellular matrix (ECM) play important roles in the
      pathological process of peritoneal fibrosis. Peritoneal matrix accumulation is a
      characteristic of peritoneal fibrosis (PF). Continuous ambulatory peritoneal
      dialysis (CAPD) patients with upregulation of transforming growth factor-beta1
      (TGF-beta1) in their drained effluent show an increased risk of PF. Inhibition of
      TGF-beta1 expression in human peritoneal mesothelial cells (HPMCs) may provide a
      potential treatment for PF. sc58236, a highly selective cyclooxygenase-2 (COX-2)
      inhibitor, reduces proteinuria and mRNA expression of TGF-beta1 and collagen III
      and IV in the remnant kidney, but their effects on ECM turnover in HPMCs are
      unknown. The aims of this study were to investigate the effects of sc58236 on TGF
      beta1 expression and matrix production in HPMCs. HPMCs were cultured from human
      omentum by an enzyme digestion method. To examine the effect of sc58236 on TGF
      beta1 and ECM secretion, HPMC were incubated in medium F12 with high
      concentration of D-glucose (4.25%) in the presence and absence of 20 microM
      sc58236. The mRNA expression of COX-2, TGF-beta1 and collagen I (Col I) were
      determined by semi-quantification reverse transcription PCR (RT-PCR).
      Prostaglandin E2 (PGE2) concentration in the culture medium was measured by
      enzyme-linked immunosorbent assay (ELISA). The protein of TGF-beta1 was
      determined by ELISA and the activity of TGF-beta1 present in the conditioned
      media was measured using the mink lung epithelial cell (MLEC) growth inhibition
      assay. Proteins of COX-2 and Col were determined by Western blot. The results
      showed that primary cultures of HPMCs do express the mRNA for COX-2 and
      stimulation of these cells with 4.25% D-glucose induced a marked increase in COX
      2 mRNA expression and protein. PGE2 expression was obviously up-regulated with
      stimulation by 4.25% D-glucose. Addition of 20 microM sc58236 significantly
      inhibited PGE2 release into the culture medium. mRNA expression and bioactive and
      total protein of TGF-beta1 and Col I were significantly increased in HPMCs
      stimulated with 4.25% D-glucose compared to the control group with F12 media,
      which was reversed in the presence of sc58236 (20 microM). An obvious decrease in
      TGF-beta1 mRNA expression and bioactive and total protein were found in sc58236
      treated groups compared to the group stimulated with 4.25% D-glucose. Exposure of
      HPMCs to sc58236 reduced Col I secretion. Sc58236 reduces the expression of TGF
      beta1 in HPMCs stimulated by 4.25% D-glucose and reduces ECM production through
      PGE2 production. These studies suggest that sc58236, a highly selective
      cyclooxygenase-2 (COX-2) inhibitor, may have a specific role in ameliorating the
      course of progressive peritoneal fibrosis under long-term peritoneal dialysis
      states.

PMID- 17196404
TI  - Structural investigation of the GlmS ribozyme bound to Its catalytic cofactor.
AB  - The GlmS riboswitch is located in the 5'-untranslated region of the gene encoding
      glucosamine-6-phosphate (GlcN6P) synthetase. The GlmS riboswitch is a ribozyme
      with activity triggered by binding of the metabolite GlcN6P. Presented here is
      the structure of the GlmS ribozyme (2.5 A resolution) with GlcN6P bound in the
      active site. The GlmS ribozyme adopts a compact double pseudoknot tertiary
      structure, with two closely packed helical stacks. Recognition of GlcN6P is
      achieved through coordination of the phosphate moiety by two hydrated magnesium
      ions as well as specific nucleobase contacts to the GlcN6P sugar ring. Comparison
      of this activator bound and the previously published apoenzyme complex supports a
      model in which GlcN6P does not induce a conformational change in the RNA, as is
      typical of other riboswitches, but instead functions as a catalytic cofactor for
      the reaction. This demonstrates that RNA, like protein enzymes, can employ the
      chemical diversity of small molecules to promote catalytic activity.

PMID- 17196405
TI  - The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in
      mice.
AB  - Oroxylin A is a flavonoid and was originally isolated from the root of
      Scutellaria baicalensis Georgi., one of the most important medicinal herbs in
      traditional Chinese medicine. The aim of this study was to investigate the
      ameliorating effects of oroxylin A on memory impairment using the passive
      avoidance test, the Y-maze test, and the Morris water maze test in mice. Drug
      induced amnesia was induced by administering scopolamine (1 mg/kg, i.p.) or
      diazepam (1 mg/kg, i.p.). Oroxylin A (5 mg/kg) significantly reversed cognitive
      impairments in mice by passive avoidance and the Y-maze testing (P<.05). Oroxylin
      A also improved escape latencies in training trials and increased swimming times
      and distances within the target zone of the Morris water maze (P<.05). Moreover,
      the ameliorating effects of oroxylin A were antagonized by both muscimol and
      diazepam (0.25 mg/kg, i.p., respectively), which are GABA(A) receptor agonists.
      Furthermore, oroxylin A (100 microM) was found to inhibit GABA-induced inward Cl(
      ) current in a single cortical neuron. These results suggest that oroxylin A may
      be useful for the treatment of cognitive impairments induced by cholinergic
      dysfunction via the GABAergic nervous system.

PMID- 17196406
TI  - Intermittent pneumatic compression (IPC) in the treatment of peripheral arterial
      occlusive disease (PAOD)--A useful tool or just another device?

PMID- 17196408
TI  - Letter to the Editors: From innumeracy to insight: the uncertainty of help versus
      harm in treatment of asymptomatic aortic aneurysms.

PMID- 17196409
TI  - UGT1A1(TA)n promoter polymorphism--a new case of a (TA)8 allele in Caucasians.
AB  - Gilbert's syndrome is a mild hereditary unconjugated hyperbilirubinemia caused by
      mutations in the bilirubin UDP-glucuronosyltransferase gene (UGT1A1). The
      causative mutation in Caucasians is almost exclusively a TA dinucleotide
      insertion in the TATA box of the UGT1A1 promoter. Affected individuals are
      homozygous for the variant promoter and have 7 instead of 6 TA repeats. The aim
      of the present study was to determine the genotypes of UGT1A1(TA)n promoter
      polymorphism in the healthy Slovenian population and to investigate the
      association of genotypes with serum bilirubin levels. 236 healthy subjects were
      genotyped by single-strand conformation polymorphism analysis, which was
      validated by sequence analysis. The frequencies of genotypes were as follows:
      (TA)(6/6) (38.1%), (TA)(6/7) (47.9%), (TA)(7/7) (13.6%). There was a
      statistically significant association of genotypes with serum bilirubin levels
      (p<0.001). Subjects with genotype (TA)(7/7) had the highest and subjects with
      genotype (TA)(6/6) the lowest total serum bilirubin levels. One individual in the
      group had the rare genotype (TA)(7/8) (0.4%). Analysis of his family showed the
      following genotypes: (TA)(6/8) in his father and sister and (TA)(7/8) in his two
      brothers. In conclusion, the frequency of UGT1A1(TA)n promoter polymorphism
      genotypes was determined for the first time in the Slovenian population and is
      similar to frequencies observed in other Caucasian populations. The extremely
      rare (TA)8 allele in Caucasians was found also in Slovenians.

PMID- 17196410
TI  - Childhood dermatomyositis associated with intracranial tumor and liver cysts.
AB  - We present a girl with dermatomyositis, liver cysts and choroid plexus papilloma
      who was treated and followed for 7 years. Muscle histology revealed an
      inflammatory muscle disease and similar changes were detected in a brain tumor
      that was surgically removed at onset. Western blot analysis of the muscle
      revealed severely reduced calpain-3 protein. She was treated with pulse
      methylprednisolone treatment (800 mg i.v. for 4 days) followed by oral prednisone
      treatment (16 mg on alternate day) for 14 months, which improved muscle strength.
      Moreover, the cystic liver formations disappeared during steroid treatment. This
      is an unusual association of muscular disorder, steroid-responsive liver cysts,
      intracranial tumor and secondary calpain-3 deficiency. We speculate that this
      association is not coincidental, but mediated by an autoimmune attack against an
      antigen that is shared among the target tissues.

PMID- 17196411
TI  - fMRI bold signal analysis using a novel nonparametric statistical method.
AB  - We present in this article a novel analytical method that enables the application
      of nonparametric rank-order statistics to fMRI data analysis, since it takes the
      omnipresent serial correlations (temporal autocorrelations) properly into
      account. Comparative simulations, using the common General Linear Model and the
      permutation test, confirm the validity and usefulness of our approach. Our
      simulations, which are performed with both synthetic and real fMRI data, show
      that our method requires significantly less computation time than permutation
      based methods, while offering the same order of robustness and returning more
      information about the evoked response when combined with/compared to the results
      obtained with the common General Lineal Model approach.

PMID- 17196412
TI  - Imaged deconvolution: a method for extracting high-resolution NMR spectra from
      inhomogeneous fields.
AB  - We present a novel method for obtaining high resolution NMR spectra in the
      presence of grossly inhomogeneous magnetic fields, such as those encountered in
      one-sided access NMR. Our method combines the well-known principle of reference
      deconvolution with NMR imaging in order to resolve spectral features with
      frequency resolution orders of magnitude smaller than the prevailing line
      broadening due to field inhomogeneity. We demonstrate that, in cases of
      inhomogeneous field line-broadening more than an order of magnitude larger than
      the spectral features to be resolved, rather than performing reference
      deconvolution on the sample as a whole, it is more favourable in terms of SNR to
      divide the target region of a sample into smaller sub-regions, by means of
      chemical shift imaging, and then to perform reference deconvolution on the
      individual sub-region spectra, finally summing the results In this way,
      significant resolution enhancements can be obtained in the presence of severe
      magnetic field inhomogeneity without an unacceptable loss in SNR.

PMID- 17196413
TI  - Effect of theophylline on endogenous hydrogen sulfide production in patients with
      COPD.
AB  - BACKGROUND: Airway inflammation plays a role in the pathogenesis of chronic
      obstructive pulmonary disease (COPD). Endogenous hydrogen sulfide (H2S) is
      involved in the physiological and pathophysiological process in systemic
      inflammation and may be involved in the pathogenesis of airway inflammation and
      airflow obstruction in COPD. The non-selective phosphodiesterase inhibitor
      theophylline has bronchodilator/anti-inflammatory properties and is widely used
      in the treatment of airways diseases. It is not fully understood whether
      endogenous H2S mediates the mechanism of theophylline anti-inflammatory effect.
      METHODS: The effect of short-term theophylline treatment on airway inflammation
      and endogenous H2S production was prospectively studied in thirty-seven patients
      with stable COPD. Patients were randomly divided into theophylline-treatment
      group (nineteen patients, orally given sustained theophylline tablets for 1
      month, 0.2g, q 12h) and control group (eighteen patients, not given any
      theophylline). Symptom score, lung function, total and differential cell counts
      in sputum, serum H2S and nitric oxide (NOx) levels, sputum and serum IL-8 levels
      were measured at baseline and 1 month later. RESULTS: No significant difference
      was found in symptom scores, lung function and other investigated experimental
      parameters at baseline between treatment and control groups, and between baseline
      and a month follow-up in control patients. Symptom scores were significantly
      lowered only in the treated patients after treatment, compared with those before
      (P<0.01). The proportion of neutrophils in sputum was significantly decreased
      (P<0.05) while that of macrophages was markedly increased (P<0.01) in the treated
      patients after treatment, compared with that before. No significant change was
      found in serum H2S and NOx levels, serum and sputum IL-8 levels before and after
      experiment in treatment group. Serum H2S level correlated positively with
      percentage of predicted FEV1 (r=0.465, P=0.005), and with proportion of sputum
      macrophages (r=0.349, P=0.05), but negatively with proportion of sputum
      neutrophils (r=-0.351, P=0.049) in all patients at baseline. CONCLUSIONS: Short
      term theophylline treatment improved symptoms and decreased sputum neutrophils in
      COPD, while serum H2S levels were not affected in our study population. Large
      samples will be needed to illustrate the effect of long-term theophylline
      treatment on inflammatory mediators and H2S generation in COPD.

PMID- 17196414
TI  - Altitude-related cough.
AB  - Cough is a troublesome condition which affects many visitors to high altitude.
      Traditionally it has been attributed to the inspiration of the cold, dry air
      which characterizes the high altitude environment. This aetiology was brought
      into question by observations and experiments in long duration hypobaric chamber
      studies in which cough still occurred despite controlled temperature and
      humidity. Anecdotally however, exercise, possibly via the associated increase in
      ventilation, does appear to precipitate cough at altitude. It is likely that the
      term, altitude-related cough, covers a number of conditions and aetiologies.
      These aetiologies are discussed and include water loss from the respiratory
      tract; high altitude pulmonary oedema; acute mountain sickness;
      bronchoconstriction; respiratory tract infections; vasomotor rhinitis and post
      nasal drip; and alterations in the central control of respiration. We hypothesize
      that there are two forms of altitude-related cough: a cough which may occur at
      relatively low altitudes and which is related to exercise and persists despite
      descent and a cough which does not occur at altitudes below 5000-6000 m and which
      improves rapidly with descent to lower altitude. The treatment of altitude
      related cough is symptomatic and frequently ineffective. Further work is required
      to understand the nature and aetiology of the cough which occurs at high altitude
      before effective therapies can be developed.

PMID- 17196415
TI  - Temperature effect on contractile activity of the Ambystoma dumerilii heart
      previously treated with isoproterenol.
AB  - The spontaneous heart rate (HR) and ventricular (V) and atrium (A) tensions (T)
      were evaluated through isolated organ assays at different temperatures in hearts
      from Ambystoma dumerilii control and treated with isoproterenol (ISO) [(150 mg/kg
      i.p. each 24 h, for 3 days)] on days 1, 5, 30 and 90 after ISO. In control
      hearts, the HR increased and the T decreased when temperature was augmented. One
      day after ISO the HR (43-24%) and T (50-25%) decreased with respect to control,
      between 8 and 24 degrees C. Five, 30 and 90 days after ISO, HR showed a gradual
      recovery with similar effect when the temperature was changed; but the AT
      increased and VT decreased at temperatures between 8 and 12 degrees C and were
      only recovered at temperatures above 12 degrees C. Our results indicate that the
      HR recovers after ISO in A. dumerilii independently of temperature. The recovery
      of AT and VT is similar to HR at temperatures higher than 12 degrees C and the
      increases in VT could be compensating the decrease in VT caused by ISO, at
      temperatures lower than 12 degrees C. The changes in heart contractile activity
      of A. dumerilii after insult show the thermic plasticity that is observed in
      ectothermic vertebrates.

PMID- 17196416
TI  - Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae for
      high-level production of isoprenoids.
AB  - Amorphadiene, a sesquiterpene precursor to the anti-malarial drug artemisinin, is
      synthesized by the cyclization of farnesyl pyrophosphate (FPP). Saccharomyces
      cerevisiae produces FPP through the mevalonate pathway using acetyl-CoA as a
      starting compound. In order to enhance the supply of acetyl-CoA to the mevalonate
      pathway and achieve high-level production of amorphadiene, we engineered the
      pyruvate dehydrogenase bypass in S. cerevisiae. Overproduction of acetaldehyde
      dehydrogenase and introduction of a Salmonella enterica acetyl-CoA synthetase
      variant increased the carbon flux into the mevalonate pathway resulting in
      increased amorphadiene production. This work will be generally applicable to the
      production of a broad range of isoprenoids in yeast.

PMID- 17196417
TI  - Transfusion safety with regards to prions: ethical, legal and societal
      considerations.
AB  - The purpose of these vignettes is to illustrate that although the dominant
      ethical, legal and societal position is based on the precautionary principle of
      deontological non-maleficence, in reality a degree of utilitarian proportionality
      arises because there is little choice but to balance proposed variant CJD risk
      management strategies against other ethical imperatives including failure of
      beneficence, non-maleficence with regard to others, autonomy and justice. There
      are no easy answers in balancing these issues, but it is important that it is
      more widely recognised that such moral judgements have to be made and that a
      wider debate in society occurs over where the balance should lie.

PMID- 17196418
TI  - Enhanced resistance to Salmonella enterica serovar Typhimurium infection in mice
      after coumarin treatment.
AB  - Coumarin and its derivatives are naturally occurring substances with multiple
      biological activities. Here we demonstrate that prophylactic peroral
      administration of coumarin or 7-hydroxycoumarin (7-OHC) enhances resistance to
      subsequent lethal Salmonella enterica Serovar Typhimurium infection in mice. 7
      OHC decreased bacterial load in liver and spleen, and enhanced phagocytosis and
      bacterial killing by macrophages when applied in vitro and in vivo. 7-OHC
      treatment induced significant NO release in peritoneal macrophage cultures. The
      observed protective effect correlated with the induction of Th1-associated
      cytokines, such as IL-12, IFN-gamma, and TNF-alpha. These data demonstrate a
      clear immunomodulatory potential of coumarins which might have important
      therapeutic implications to enhance resistance to infection.

PMID- 17196419
TI  - The envelope glycoprotein domain III of dengue virus serotypes 1 and 2 inhibit
      virus entry.
AB  - Dengue virus (DV) is a flavivirus and its urban transmission is maintained
      largely by its mosquito vectors and vertebrate host, often human. In this study,
      investigation was carried out on the involvement of domain III of the envelope
      (E) glycosylated protein of dengue virus serotypes 1 and 2 (DV-1 and DV-2 DIII)
      in binding to host cell surfaces, thus mediating virus entry. Domain III protein
      of flavivirus can also serve as an attractive target in inhibiting virus entry.
      The respective DV DIII proteins were expressed as soluble recombinant fusion
      proteins before purification through enzymatic cleavage and affinity
      purification. The purified recombinant DV-1 and DV-2 DIII proteins both
      demonstrated the ability to inhibit the entry of DV-1 and DV-2 into HepG2 cells
      and C6/36 mosquito cells. As such, the DV DIII protein is indeed important for
      the interaction with cellular receptors in both human and mosquito cells. In
      addition, this protein induced antibodies that completely neutralized homologous
      dengue serotypes although not with the same efficiency among the heterologous
      serotypes. This observation may be of importance when formulating a generic
      vaccine that is effective against all dengue virus serotypes.

PMID- 17196421
TI  - Dengue-3 virus genomic differences that correlate with in vitro phenotype on a
      human cell line but not with disease severity.
AB  - We compared the full genome sequence of nine clinical isolates of dengue virus
      obtained during an epidemic of dengue-3 in French Polynesia in 1989, from
      patients with various presentations of disease. The isolates, all belonging to
      Genotype I, had 25 amino acid substitutions. There was no association with
      disease severity. When cultured in the K562 human erythroleukemia cell line, the
      isolates induced a range of cell growth inhibitions that was not associated with
      the degree of disease severity. By contrast, some substitutions--charge changes
      in NS1 and NS5, side-chain differences in NS1, loss of the E-153 potential
      glycosylation site, and 11 nucleotide insertions in the 3'UTR--that have been
      suggested to result in an increase or attenuation of dengue infection, appeared
      to be associated with the level of inhibition. These data represent the first
      documented study of an association between differences in the full dengue-3
      genome of clinical isolates and the in vitro phenotype of these isolates on a
      human cell line.

PMID- 17196420
TI  - Gliotoxin from Aspergillus fumigatus affects phagocytosis and the organization of
      the actin cytoskeleton by distinct signalling pathways in human neutrophils.
AB  - Gliotoxin is a mycotoxin having a considerable number of immuno-suppressive
      actions and is produced by several moulds such as Aspergillus fumigatus. In this
      study, we investigated its toxic effects on human neutrophils at concentrations
      corresponding to those found in the blood of patients with invasive
      aspergillosis. Incubation of the cells for 10min with 30-100ng/ml of gliotoxin
      inhibited phagocytosis of either zymosan or serum-opsonized zymosan without
      affecting superoxide production or the exocytosis of specific and azurophil
      granules. Gliotoxin also induced a significant re-organization of the actin
      cytoskeleton which collapsed around the nucleus leading to cell shrinkage and the
      disappearance of filopodia. This gliotoxin-induced actin phenotype was reversed
      by the cAMP antagonist Rp-cAMP and mimicked by pCPT-cAMP indicating that it
      probably resulted from the deregulation of intracellular cAMP homeostasis as
      previously described for gliotoxin-induced apoptosis. By contrast, gliotoxin
      induced inhibition of phagocytosis was not reversed by Rp-cAMP but by arachidonic
      acid, another member of a known signalling pathway affected by the toxin. This
      suggests that gliotoxin can affect circulating neutrophils and favour the
      dissemination of A. fumigatus by inhibiting phagocytosis and the consequent
      killing of conidia.

PMID- 17196422
TI  - Polyarticular arthritis secondary to Mycobacterium bovis infection: an unusual
      clinical presentation.
AB  - We describe a 37-year-old Mexican man with incapacitating polyarticular arthritis
      secondary to Mycobacterium bovis infection. A dermatologist diagnosed psoriasis
      two years before admission. One year later due to symmetric ankle and knee
      arthritis, he was treated with three doses of etanercept. The arthritis extended
      to the carpus and metacarpophalangeal joints. Multifocal dactylitis and a left
      ankle periarticular abscess were documented. Concomitantly he developed fever,
      cough, and adenopathies. Ankle MRI showed osteomyelitis of the calcaneous with a
      posterior abscess. A CT-body scan documented mild pleural effusion that
      corresponded to an exudate. An ankle aspiration yielded a caseous fluid with acid
      fast bacilli. Knee and ankle synovial biopsies documented a granulomatous
      synovitis. A lymph node biopsy showed granulomas with caseous necrosis. After 1
      month, Mycobacterium bovis was isolated from these tissues. Antituberculous
      regimen was started with satisfactory response. Although largely eradicated,
      bovine tuberculosis still occurs. Nevertheless, the clinical presentation as
      polyarthritis is very uncommon and represents a diagnostic challenge.

PMID- 17196423
TI  - Effects of osteoporosis medications on bone quality.
AB  - In clinical practice, the quantitative evaluation of bone tissue relies on dual
      energy X-ray absorptiometry (DXA) measurements of bone mineral density (BMD)
      values, which are closely associated with the risk of osteoporotic fracture.
      However, only a small fraction of the antifracture effect of bone resorption
      inhibitors is ascribable to BMD gains (4% with raloxifene and 16-28% with
      alendronate and risedronate). Bone quality encompasses a number of bone tissue
      properties that govern mechanical resistance, such as bone geometry, cortical
      properties, trabecular microarchitecture, bone tissue mineralization, quality of
      collagen and bone apatite crystal, and presence of microcracks. All these
      properties are dependent on bone turnover and its variations. In populations, the
      decreases in bone resorption markers achieved with resorption inhibitors may
      predict in part the decrease in fracture risk. At the spine, however, this
      correlation exists down to a 40% fall in bone resorption markers; larger drops
      did not provide further protection against fractures in patients taking
      risedronate in one evaluation of this relationship. Osteoporosis medications can
      exert favorable effects on bone size and cortical thickness. Such effects have
      been documented with teriparatide (PTH 1-34), which is the unique purely anabolic
      treatment for osteoporosis available to date. More surprising are the favorable
      effects on bone size seen with some of the bone resorption inhibitors such as
      neridronate in adults with osteogenesis imperfecta. Similarly, estrogens and
      alendronate can increase femoral neck size in postmenopausal women. Preservation
      of the trabecular microarchitecture was demonstrated first with risedronate and
      subsequently with alendronate. In placebo-controlled studies, a deterioration in
      trabecular microarchitecture occurred within 1 to 3 years in the placebo groups
      but not in the bisphosphonate groups. Teriparatide, in contrast, improves
      trabecular microarchitecture, in particular by increasing connectivity and
      improving the plate-rod distribution. The minerals within trabecular or cortical
      bone can be evaluated using microradiography or synchrotron micro-computed
      tomography. Marked or prolonged secondary mineralization may result in poor bone
      quality. Increased bone mineralization is among the key effects of bone
      resorption inhibitors, most notably bisphosphonates. Prolonged use of the most
      potent bisphosphonates may lead to unwanted effects related to excessive
      mineralization. Microcracks may play a physiological role; however, a large
      number of microcracks may be deleterious via an effect on osteocytes. Excessive
      mineralization may promote the development of multiple microcracks. Studies of
      bone crystal and collagen properties with several bone resorption inhibitors,
      including risedronate and raloxifene, showed no harmful effects. An increasing
      number (several hundreds) of mandibular osteonecrosis associated with
      bisphosphonate therapy has been reported. The typical patient was receiving
      injectable bisphosphonate therapy for bone cancer and had undergone dental work
      shortly before bisphosphonate administration. The mechanism of this adverse
      effect is poorly understood.

PMID- 17196424
TI  - [Tissue resistance: what about tension-free?].
AB  - OBJECTIVES: The purpose is to quantify objective tissue resistances before
      healing of prostheses used in pelvic floor surgery. PATIENTS AND METHODS: We
      measured tissue resistances offered to five types of meshes by four classical
      surgical routes. We also tested the incidence of the modification of the width of
      meshes on tissue resistance. This study was realized on frozen cadavers, by pull
      on prostheses just after implantation. Tests are realized with a dynamometer and
      results obtained in Newton. RESULTS: In the Retzius space, TVT offers a better
      resistance than IVS or LIFT meshes. We did not bring to the fore a significant
      difference between four routes for 1 cm wide prosthesis. The increase of width of
      Prolene meshes improves their resistance in tissues and thus quality of their
      fixation. We underscore a better resistance of the trans sacrospinous route with
      regard to the trans muscular one. DISCUSSION AND CONCLUSION: The increase of
      resistance is bound to the increase of the contact area between the prosthesis
      and the tissues. This increase of resistance should be taken into account in
      prolapse surgery: constraints are stronger than for stress incontinence. The
      posterior arms of meshes have to measure more than 1 cm wide and be set up
      through the sacrospinous ligament rather than through the elevator muscles. The
      type of knitting of prostheses is important and influences the resistance in
      tissues in the immediate postoperative time. Manufacturers should be interested
      in conceiving specific meshes for the tension-free fixation, with special and
      adapted mechanical properties.

PMID- 17196425
TI  - [Pregnancy in obese patients: which risks is it necessary to fear?].
AB  - OBJECTIVE: To evaluate the deleterious effects of maternal obesity on obstetrical
      complications and neonatal outcomes. PATIENTS AND METHODS: Historical cohort
      study including all patients delivered in our maternity between 1st January 2002
      and 31st December 2004. Intra uterine death and fetal loss before 22 weeks were
      excluded. Women were categorized by the Body Mass Index: less than 25, between 25
      and 30, and more than 30. Maternal data, obstetrical complications, labor and its
      complications, and neonatal outcomes were studied. RESULTS: During these 3 years,
      23.5% (1336/5686) of patients were overweight and 7.5% (425/5686) were obese.
      Obstetrical pathologies (gestational diabetes mellitus, hypertension,
      preeclampsia and fetal macrosomia) and labour induction were more significantly
      frequent in obese patients (P < 0.01). We noted twice more caesarean sections
      during labour in obese patients. The rate of artificial placental delivery was
      significantly higher in obese patients (P < 0.01). Obese patients with prior
      caesarean sections had a rate of vaginal delivery significantly lower than non
      obese patients with prior C-sections (23.6 vs 43.8%; P < 0.01). Mean children
      birth weight was significantly higher in obese patients (3305 vs 3181 g; P <
      0.01) with no impact on Apgar score. DISCUSSION AND CONCLUSION: Our study
      confirms that obesity is responsible for major obstetrical complications, for
      what should no doubt be considered as high risk pregnancies. Our practices must
      take these complications into account by ensuring an adapted and early management
      in order to improve maternal and neonatal issues.

PMID- 17196426
TI  - [Struma ovarii, a rare form of ovarian tumor].
AB  - Struma ovarii, a rare form of ovarian tumor, represents less than 3% of ovarian
      teratomas. The peak frequency occurs during the fifth decade of life. Diagnosis
      is usually a surprise of pelvic ultrasound or histological analysis. Surgery is
      the main mode of treatment and prognosis is excellent. Struma ovarii can be
      associated with thyroid biology abnormalities, or exceptionally become malignant,
      and thus managed as a thyroid cancer.

PMID- 17196427
TI  - Raman, IR and SERS spectra of methyl(2-methyl-4,6
      dinitrophenylsulfanyl)ethanoate.
AB  - Methyl(2-methyl-4,6-dinitrophenylsulfanyl)ethanoate was prepared by nucleophilic
      substitution. FT-IR and FT-Raman spectra of methyl(2-methyl-4,6
      dinitrophenylsulfanyl)ethanoate were recorded and analyzed. Surface-enhanced
      Raman scattering (SERS) spectrum was recorded on a silver colloid. The vibrationl
      wavenumbers were computed by density functional theoretical (DFT) computations at
      the B3LYP/6-31G* level and they were found to be in good agreement with the
      experimental values. The molecule is adsorbed on the silver surface with the
      benzene ring in a 'tilted orientation'.

PMID- 17196428
TI  - Vibrational spectra, NMR and theoretical studies of the enantiomers and rotamers
      of alpha-cypermethrin.
AB  - NMR, infrared and Raman vibrational spectra of alpha-cypermethrin have been
      measured at room temperature. Infrared spectra were also recorded to low
      temperature. The spectra were analyzed by means of ab initio calculations. The
      conformational space of both enantiomers and some rotamers A, B and C of alpha
      cypermethrin has been scanned using molecular dynamics and complemented with
      functional density calculations that optimize the geometry of the lowest-energy
      conformers of each species as obtained in the simulations. The vibrational
      frequencies and the 1H and 13C NMR chemical shifts were assigned using functional
      density calculations. The molecular electrostatic potential maps were obtained
      and analyzed.

PMID- 17196429
TI  - Revised reference value for pentachlorophenol in morning urine.
AB  - Reference values are continuously derived by the Human Biomonitoring Commission
      of the German Federal Environment Agency to give help in assessing the exposure
      of individuals or population groups in comparison to the background exposure. As
      environmental conditions may change reference values should be checked
      periodically and they have to be updated, if new data become available. The
      results of the German Environmental Survey 1998 (GerES III) showed the decreasing
      pentachlorophenol (PCP) exposure of the German adult population. Therefore, the
      reference value for PCP in morning urine was lowered: from 8 to 5 microg/l for
      adults (aged 18-69 years) living in homes where wood preservatives had not been
      used.

PMID- 17196431
TI  - Altered sexual health and quality of life in women prior to hematopoietic cell
      transplantation.
AB  - The purpose of this cross-sectional descriptive study is to define sexual
      dysfunction and menopausal symptoms in women following cytotoxic or
      immunosuppressive medication for the treatment of malignant or life-threatening
      hematolymphoid diseases. These women were preparing to undergo hematopoietic cell
      transplantation (HCT) as the next step in their treatment plan. It is assumed
      that sexual dysfunction and symptoms of premature menopause are more pronounced
      post-HCT due to the intensity of the preparative regimen on the hypothalamic
      pituitary-gonadal axis. This study included 48 pre-menopausal women and 28
      spouses/partners. Data were collected using five self-report instruments
      (demographic and medical, the Female Sexual Function Index, the Menopause
      specific Quality of Life, the Psychosocial Adaptation to Illness Scale, and a
      global quality of life score). The main research variables were female sexual
      functioning, symptoms of menopause, and quality of life. The findings indicate
      that 73% of women report decreased libido and 48% report dissatisfaction with
      their overall sex life. Hot flashes, the most common symptom of menopause are
      reported by 46% and 27% report the hot flashes moderate to severe in intensity.
      Vaginal dryness was reported by 35% with 23% reporting the vaginal dryness to be
      moderate to severe. The mean quality of life (QOL) score in women was 69+/-25
      with a range of 2-100 (on a scale of 0-100 with 100 being an excellent QOL). The
      findings indicate that women treated with standard dose chemotherapy and
      immunosuppressive therapy for malignant and life-threatening hematolymphoid
      diseases experience alterations in sexual health and symptoms of premature
      menopause. The results show that the desire, arousal, and orgasm phase of the
      sexual response cycle are altered. Additionally, nearly half of the women are
      experiencing hot flashes, the most common symptom of menopause and over a third
      report vaginal dryness. There are statistically significant correlations between
      altered sexual health, menopausal symptoms, and QOL scores.

PMID- 17196430
TI  - The mystery of coronary artery spasm.
AB  - Coronary artery spasm is an important cause of chest pain and myocardial
      ischaemia. It can be defined as an exaggerated contractile response of epicardial
      coronary artery smooth muscle to various stimuli but the underlying mechanism is
      not well understood. Recent studies have shown that the loss of endothelial
      vasodilatory function in conjunction with an increase in vascular smooth muscle
      constrictor sensitivity to calcium are the likely predisposing conditions for
      coronary spasm. This review highlights current understanding of the
      pathophysiology, predisposing factors, diagnostic and therapeutic approaches for
      coronary spasm.

PMID- 17196432
TI  - The lymphocyte guard-IANs: regulation of lymphocyte survival by IAN/GIMAP family
      proteins.
AB  - The life-or-death decision of immune cells makes an essential contribution to
      immune-system development and the regulation of immune responses. A new family of
      cell-survival regulators expressed in lymphocytes, termed immune-associated
      nucleotide-binding proteins (IANs) [also known as GTPase of immunity-associated
      proteins (GIMAPs)], has been described. The IAN/GIMAP family consists of GTP
      binding proteins that share a unique primary structure and whose expression is
      finely regulated by T-cell receptor signals. Recent studies have shown that
      IAN/GIMAP family proteins crucially regulate the survival of T cells during
      development, selection and homeostasis, and are possibly linked to the onset of T
      lymphopenia, leukemia and autoimmunity. IAN/GIMAP family proteins might also take
      part in mitochondrial regulation of lymphocyte apoptosis by interacting with Bcl
      2 family proteins.

PMID- 17196433
TI  - Psychosexual function and impact of gynaecological cancer.
AB  - A diagnosis of gynaecological cancer and its treatment are usually associated
      with many physical and psychological changes, both as a result of the diagnosis
      itself and of the usual treatments of surgery, radiotherapy and/or several months
      of chemotherapy. Patients often experience symptoms such as fatigue, abdominal
      swelling and pain, and suffer from emotional distress and disturbances of their
      life style. Sexual functioning can also be affected. Often there are
      physiological difficulties, such as vaginal dryness, together with psychological
      distress and relationship problems. This chapter discusses the ways in which
      gynaecological cancer can impact sexual functioning, and presents findings from a
      research project that was undertaken to begin to understand how sexual
      functioning can be affected by ovarian cancer. The article also makes
      recommendations for how health-care professionals can help women to cope better
      with psychosexual dysfunction following a diagnosis of a gynaecological cancer.

PMID- 17196434
TI  - Psychological aspects of perinatal loss.
AB  - After perinatal loss, parents experience painful grief. Fathers and mothers show
      the same pattern of symptoms, but generally mothers' distress is more intense.
      Grief should be sympathetically acknowledged by health professionals, and parents
      should be reassured that their feelings are normal and that recovery may take
      many months. Intense depression lasting more than 6 months may require
      psychological treatment. There is some evidence that delaying conception for a
      year may allow an easier pregnancy psychologically. The common practice of
      encouraging parents to have contact with a dead infant is not evidence-based and
      may have adverse effects, including inducing symptoms of post-traumatic stress
      disorder. A protocol of postnatal follow-up allows parents to get appropriate
      information about the loss, including possible problems and timing of another
      pregnancy. The subsequent pregnancy is stressful, and health professionals should
      recognize that parents may suffer significant anxiety.

PMID- 17196435
TI  - Impact of ribavirin dose reductions in hepatitis C virus genotype 1 patients
      completing peginterferon alfa-2a/ribavirin treatment.
AB  - BACKGROUND & AIMS: To maximize sustained virologic response (SVR) in patients
      with chronic hepatitis C virus (HCV) infection, treatment with pegylated
      interferon and ribavirin has been genotype-specific (1 vs non-1). We evaluated
      the effects of ribavirin and peginterferon alfa-2a dose reductions on SVR in
      patients infected with HCV genotype 1. METHODS: Data were pooled from 569
      patients enrolled in 2 phase III trials of 48 weeks of treatment with
      peginterferon alfa-2a and ribavirin. All patients were evaluated for the effect
      of cumulative drug exposure on 4- and 12-week responses, and the 427 patients who
      completed treatment were evaluated for effect of drug exposure on SVR. RESULTS:
      Of patients who completed treatment, more had reductions (< or =97% cumulative
      dose) of ribavirin than of peginterferon alfa-2a (43% vs 27%). Neither early
      virologic response nor SVR was affected adversely by ribavirin reductions when
      the cumulative ribavirin exposure was greater than 60%. The SVR was reduced
      significantly (P = .0006) in patients with less than the 60% cumulative ribavirin
      dose and was associated with prolonged periods of dose reduction, temporary
      interruptions, or premature cessation of ribavirin. Ribavirin dose reductions had
      minimal impact on SVR in patients who achieved rapid virologic response, defined
      as undetectable HCV RNA levels after 4 weeks, even when they received less than
      the 60% cumulative ribavirin dose. In contrast, SVR was reduced markedly in
      patients who had ribavirin dose reductions and did not achieve rapid virologic
      response. CONCLUSIONS: Minor ribavirin dose reductions to manage adverse events
      do not appear to affect SVR adversely, unless cumulative exposure is less than
      60%. Prospective studies, however, are required to establish the impact of
      ribavirin dose reduction on SVR.

PMID- 17196436
TI  - Development of bariatric surgery-specific risk assessment tool.
AB  - BACKGROUND: Administrative databases have increasingly been used to assess
      bariatric surgery outcomes, resulting in policy recommendations about bariatric
      practice. However, surgical outcomes must be risk adjusted to compare patients of
      varying potential risk fairly with those to whom the policies will apply. To
      date, the risk adjustment tools used for database analysis of bariatric surgical
      outcomes have been those designed for other purposes, and their sensitivity for
      bariatric outcomes has not been established. METHODS: Bariatric surgical
      procedures contained in the National Hospital Discharge Summary for 1993-2003
      were assembled into a database. The standard set of Elixhauser co-morbidity
      variables used by the Agency for Healthcare Research and Quality were entered
      into the database. Those variables that were significantly associated with
      adverse outcomes were entered into a stepwise-elimination logistic regression
      equation, yielding a set of variables related to adverse outcomes from bariatric
      surgery. These were then prospectively applied to another database (the National
      Inpatient Survey) to determine their sensitivity for predicting outcomes and were
      compared with the commonly used Charlson score. RESULTS: The variables
      significantly correlating with bariatric adverse events included chronic
      pulmonary disease, hypertension, diabetes with chronic complications, fluid and
      electrolyte disorders, deficiency anemias, and depression. Age and male gender
      were also signficantly related to adverse events. The c-index (a correlative
      index, with .5 showing no, and 1, a perfect, relationship) for bariatric surgery
      mortality with the Charlson index is .52. For the Elixhauser-based system we
      developed, it is .72. CONCLUSIONS: We have developed a new risk-adjustment tool
      for bariatric surgery outcomes studies that use administrative databases. Its
      performance was clearly better than that of the commonly used Charlson co
      morbidity score. Bariatric studies that have used the Charlson index should not
      be considered adequately risk adjusted.

PMID- 17196437
TI  - Venous thromboembolism in bariatric surgery patients: an update of risk and
      prevention.

PMID- 17196438
TI  - Medicolegal analysis of 100 malpractice claims against bariatric surgeons.
AB  - BACKGROUND: Very few studies have addressed malpractice litigation specific to
      bariatric surgery. This study was designed to analyze litigation trends in
      bariatric surgery to prevent further lawsuits and improve patient care. METHODS:
      A total of 100 consecutive bariatric lawsuits were reviewed by a consortium of
      experienced bariatric surgeons and an attorney specializing in medical
      malpractice. RESULTS: Of the 100 lawsuits, 45% were reviewed for defense
      attorneys. The mean patient age was 40 years (range 18-65), 75% were women, 81%
      had a body mass index of <60, 31% were diabetic, and 38% had sleep apnea. Of the
      surgeons, 42% had <1 year of experience, and 26% had done <100 cases. Although
      69% of the physicians were members of the American Society of Bariatric Surgery,
      only 22% had detailed consent forms. The surgical procedures were performed
      between 1997 and 2005 and included Roux-en-Y gastric bypass (78% total, 33% open,
      and 45% laparoscopic), vertical banded gastroplasty (3%), minigastric bypass
      (6%), biliopancreatic diversion/duodenal switch (4%), and revision (9%). Of the
      100 cases, 32% involved an intraoperative complication and 72% required
      additional surgery. The most common adverse events initiating litigation were
      leaks (53%), intra-abdominal abscess (33%), bowel obstruction (18%), major airway
      events (10%), organ injury (10%), and pulmonary embolism (8%). From these
      injuries, 53 patients died, 28% had a full recovery, 12% had a minor disability,
      and 7% had major disabilities. Evidence of potential negligence was found in 28%
      of cases. Of these cases, 82% resulted from a delay in diagnosis and 64% from
      misinterpreted vital signs. CONCLUSIONS: This study found that leaks and delayed
      diagnosis were the most common cause of litigation. Even experienced bariatric
      surgeons should understand the most common errors made by others to prevent
      complications and avoid litigation.

PMID- 17196439
TI  - Natural history of morbid obesity without surgical intervention.
AB  - BACKGROUND: To study the mortality among morbidly obese patients qualifying for
      bariatric surgery. Mortality from bariatric surgery for morbid obesity has been
      widely reported; however, little is known about the mortality in morbidly obese
      patients who defer surgery. METHODS: Consecutive patients evaluated for bariatric
      surgery with an initial encounter between 1997 and 2004 were identified. The
      Social Security Death Index and office records were used to identify mortality
      through 2006. We conducted telephone interviews to determine whether the 305
      patients who did not undergo bariatric surgery at our institution had undergone
      the surgery elsewhere. Using Cox proportional hazards models, we compared the
      mortality in patients undergoing surgery with that of those who did not. To
      evaluate bias resulting from missing data, we conducted analyses assuming that
      all patients with missing data had (1) undergone surgery and (2) not undergone
      surgery. RESULTS: A total of 908 patients underwent bariatric surgery (880
      patients at our institution and 28 patients elsewhere). A total of 112 patients
      did not undergo surgery. Data regarding surgery on 165 patients could not be
      obtained. The mortality in those patients who did not undergo surgery was 14.3%
      compared with 2.9% for those who did undergo surgery. Adjusting for age, gender,
      and body mass index, patients who had undergone surgery had an 82% reduction in
      mortality (hazard ratio 0.18, 95% confidence interval 0.09-0.35, P <.0001).
      Sensitivity analysis, assuming that all patients with missing data received
      surgery resulted in an 85% mortality reduction (P <.001) and assuming that
      patients did not receive surgery resulted in a 50% mortality reduction (P = .04).
      CONCLUSIONS: Mortality among morbidly obese patients without surgery was 14.3%
      during the study period. Surgical intervention offered a 50%-85% mortality
      reduction benefit.

PMID- 17196440
TI  - Use of Polyflex stents in treatment of acute esophageal and gastric leaks after
      bariatric surgery.
AB  - BACKGROUND: This study examined the feasibility of using Polyflex stents in the
      treatment of enteric leaks after various bariatric operations. Chronic and acute
      leaks were treated. METHODS: We performed a retrospective case series review.
      Four patients received 6 Polyflex stents to treat complications of bariatric
      surgery. Two presented with early sepsis before stenting. One presented with
      abdominal pain. One presented with a chronic persistent fistula with an
      associated abscess. Stenting was performed under endoscopy with fluoroscopic
      guidance. The stents were left in place for 6 weeks. RESULTS: All patients
      tolerated a clear liquid diet within 24 hours of stenting and were able to be
      advanced to a pureed diet. All patients improved clinically after stenting. Three
      patients with acute leaks sealed their leaks after stent placement. One patient
      with a chronic leak persisted and required operative closure after a second stent
      was placed and failed. All patients experienced short-term nausea, as well as
      early satiety that lasted the duration of the stenting. One patient experienced
      hypersialisis while the stent was in place. Two stents migrated, although this
      had no effect on leak closure. One patient had an anastomotic stenosis
      successfully treated with a second stent. CONCLUSIONS: Polyflex stents are useful
      in bypassing acute upper intestinal leaks after various bariatric operations.
      They provide a temporary bridge for wound healing with continued oral intake.
      Stenting provides a minimally invasive option in the management of acute leaks
      and, in our experience, had no serious associated morbidity.

PMID- 17196442
TI  - Gastric bypass reduces biochemical cardiac risk factors.
AB  - BACKGROUND: Coronary artery disease (CAD) is the leading cause of death in the
      United States, with obesity as a leading preventable risk factor for CAD. Certain
      biochemical markers have demonstrated strong prediction for cardiovascular
      events. We hypothesized that in addition to weight reduction, gastric bypass will
      also induce a salutary effect on the biochemical cardiac risk factors. METHODS:
      At a single academic institution, from 2003 to 2004, we measured the biochemical
      cardiac risk factors in gastric bypass patients preoperatively and at 3, 6, and
      12 months postoperatively. These risk factors included total cholesterol, high
      density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, total
      cholesterol/HDL cholesterol ratio, triglyceride/HDL cholesterol ratio,
      triglycerides, lipoprotein A, high-sensitivity C-reactive protein, and
      homocysteine. The data were analyzed using the Wilcoxon signed rank test.
      RESULTS: The mean age of the 356 patients was 43 years; 84% were women; the mean
      body mass index was 47 kg/m(2); 33% were diabetic; 50% were hypertensive; 23%
      were taking lipid-lowering medications; and 2% had known CAD. Significant
      improvement occurred in the biochemical cardiac factors from preoperatively to 12
      months. The beneficial changes were as follows: total cholesterol, 192 mg/dL
      preoperatively to 166 mg/dL at 12 months; HDL cholesterol, 46 mg/dL
      preoperatively to 54 mg/dL at 12 months; low-density lipoprotein, 125 mg/dL
      preoperatively to 88 mg/dL at 12 months; total cholesterol/HDL cholesterol ratio,
      4 preoperatively to 3 at 12 months; triglyceride/HDL cholesterol ratio, 3
      preoperatively to 2 at 12 months; triglycerides, 133 mg/dL preoperatively to 92
      mg/dL at 12 months; lipoprotein A, 14 mg/dL preoperatively to 13 mg/dL at 12
      months; high-sensitivity C-reactive protein, 8 mg/L preoperatively to 1 mg/L; and
      homocysteine, 10 mumol/L preoperatively to 8 mumol/L at 12 months. CONCLUSIONS:
      The results of our study have shown that gastric bypass significantly improves
      all biochemical markers of CAD risk, particularly C-reactive protein, which had
      an 80% reduction. As a result, gastric bypass decreases the cardiac risk by both
      weight loss and advantageous alterations of biochemical cardiac risk factors.

PMID- 17196443
TI  - Surgical revision of loop ("mini") gastric bypass procedure: multicenter review
      of complications and conversions to Roux-en-Y gastric bypass.
AB  - BACKGROUND: The claim that the "mini"-gastric bypass (MGB) procedure with its
      loop gastrojejunostomy is safer and equally effective to the Roux-en-Y gastric
      bypass (RYGB) procedure has been promoted before validation. Rumors of unreported
      complications and the accuracy of follow-up are additional concerns. This study
      was undertaken to identify MGB patients who require or required revisional
      surgery at 5 hospitals within the region of the United States where the MGB
      procedure originated to assess the claim that revision to RYGB is rarely needed.
      METHODS: The databases of 5 medical centers were retrospectively searched to
      identify patients undergoing surgical revision after a MGB procedure, all of
      which had been done elsewhere. RESULTS: A total of 32 patients were identified
      who presented with complications after undergoing an MGB procedure and required
      or require revisional surgery. The complications included gastrojejunostomy leak
      in 3, bile reflux in 20, intractable marginal ulcer in 5,
      malabsorption/malnutrition in 8, and weight gain in 2. Of the 32 patients, 21
      required conversion to RYGB and an additional 5 have planned revisions in the
      future. Also, 2 patients were treated with Braun enteroenterostomies and 4
      required 1 or more abdominal explorations. CONCLUSIONS: The results of this
      preliminary review have confirmed that MGB does require revision in some patients
      and that conversion to RYGB is a common form of revision. A national registry to
      record the complications and number of revisions is proposed to gain insight into
      the need for revision after MGB and other nontraditional bariatric procedures.

PMID- 17196444
TI  - Starting from scratch: program development and lessons learned from HIV vaccine
      trial counseling in Thailand.
AB  - Counseling for participants in preventive HIV vaccine trials has been an area of
      continuing concern because of the need to address possible behavioral side
      effects (e.g., increased risk behavior because trial participants believe they
      may have received an active, effective vaccine) and social harms (e.g.,
      discrimination in health care or employment because of vaccine-induced
      seropositivity on commercial HIV tests). Yet, the data on behavioral effects and
      social harms are limited and rather little detail has been provided regarding the
      counseling provided in current or past trials. This paper summarizes conceptual,
      cultural, and practical considerations in the development of a counseling program
      for HIV vaccine trials and provides examples from work done in the context of
      Phase I/II vaccine trials in Thailand.

PMID- 17196445
TI  - Increased expression of p53 enhances transcription-coupled repair and global
      genomic repair of a UVC-damaged reporter gene in human cells.
AB  - Ultraviolet (UV) light-induced DNA damage is repaired by nucleotide excision
      repair, which is divided into two sub-pathways: global genome repair (GGR) and
      transcription-coupled repair (TCR). While it is well established that the GGR
      pathway is dependent on the p53 tumour suppressor protein in human cells, both
      p53-dependent and p53-independent pathways have been reported for TCR. In the
      present work, we investigated the role of p53 in both GGR and TCR of a UVC
      damaged reporter gene in human fibroblasts. We employed a non-replicating
      recombinant human adenovirus, AdCA17lacZ, that can efficiently infect human
      fibroblasts and express the beta-galactosidase (beta-gal) reporter gene under the
      control of the human cytomegalovirus promoter. We examined host cell reactivation
      (HCR) of beta-gal expression for the UVC-treated reporter construct in normal
      fibroblasts and in xeroderma pigmentosum (XP) and Cockayne syndrome (CS)
      fibroblasts deficient in GGR, TCR, or both. HCR was examined in fibroblasts that
      had been pre-infected with Ad5p53wt, which expresses wild-type p53, or a control
      adenovirus, AdCA18luc, which expresses the luciferase gene. We show that
      increased expression of p53 results in enhanced HCR of the UVC-damaged reporter
      gene in both untreated and UVC-treated cells for normal, CS-B (TCR-deficient),
      and XP-C (GGR-deficient), but not XP-A (TCR- and GGR-deficient) fibroblasts.
      These results indicate an involvement of p53 in both TCR and GGR of the UV
      damaged reporter gene in human cells.

PMID- 17196446
TI  - Role of Claspin in regulation of nucleotide excision repair factor DDB2.
AB  - The replication checkpoint protein Claspin is important for maintenance of
      genomic stability and is required for cells to overcome genotoxic stress. Upon UV
      induced DNA damage, Claspin is required for activation of the ATR-mediated DNA
      damage checkpoint response, leading to arrest of DNA replication and inhibition
      of cell cycle progression. Located at the DNA replication fork, Claspin is also
      suggested to monitor replication and sense damage. Our present studies in HeLa
      cells demonstrate associations between the Claspin/ATR-related DNA damage
      checkpoint response and the global genomic nucleotide excision repair pathway.
      siRNA-mediated knockdown of Claspin abolishes the UV-induced degradation of DDB2
      and impairs the co-localization of DDB2 to DNA damage sites. Thus, the presence
      of Claspin is required for the total turnover of DNA damage binding protein DDB2,
      as well as for its functionality in DNA damage recognition. Claspin, however,
      seems not to be required for maintaining the cellular level of the NER factor XPC
      and its UV-induced post-translational modifications. Co-localization of XPC with
      DNA lesions is also intact in the absence of Claspin as is the repair of the UV
      induced lesions CPD and 6-4PP. Claspin itself may be directly responsible for
      physical interaction between the two pathways since Claspin is able to associate
      with DDB1, DDB2 and XPC. Taken together, these findings reveal physical and
      functional interplay between Claspin and NER-related proteins and demonstrate
      crosstalk between the DNA damage checkpoint control and DNA damage repair
      pathways.

PMID- 17196448
TI  - Determination of 19 antiretroviral agents in pharmaceuticals or suspected
      products with two methods using high-performance liquid chromatography.
AB  - Three classes of antiretroviral agents are usually available for the treatment of
      HIV infection: nucleoside reverse transcriptase inhibitors (IN), non-nucleoside
      reverse transcriptase inhibitors (INN) and protease inhibitors (IP). Two methods
      by reversed-phase liquid chromatography were developed for the analysis of 19
      antiretroviral molecules belonging to these three therapeutic classes and used in
      medicinal products. Both of these HPLC techniques use a C18 column and UV
      detection. The first method is for IN family analysis and allows eight molecules
      to be separated: zalcitabine, lamivudine, amdoxovir, emtricitabine, didanosine,
      stavudine, zidovudine and abacavir. The second method is for INN and IP family
      analysis and allows 11 molecules to be separated: fosamprenavir, nevirapine,
      indinavir, amprenavir, saquinavir, atazanavir, ritonavir, lopinavir, efavirenz,
      nelfinavir and tipranavir. The combination of these two methods makes possible
      the quality control of mono-, bi- or tri-therapy pharmaceutical products and the
      detection of illegal products sold particularly in developing countries.

PMID- 17196447
TI  - Ghrelin and leptin levels in young adults with cystic fibrosis: relationship with
      body fat.
AB  - BACKGROUND: Ghrelin and leptin are hormones implicated in energy balance
      coordination and body weight regulation. There are conflicting data regarding the
      levels and role of leptin while ghrelin has not been studied in CF. The aim of
      this study was to investigate fasting serum ghrelin and leptin levels in CF
      adolescents as compared to healthy controls and analyze their association with
      body fat. METHODS: Fourteen CF adolescents having pancreatic insufficiency and
      twenty healthy adolescents were enrolled in the study. Diabetic patients were
      excluded. In all participants' height, weight, body mass index (BMI) and body fat
      % (BF %) were estimated. Ghrelin and leptin levels were determined after an
      overnight fast. RESULTS: Weight, BMI and BF% were significantly lower in CF
      adolescents than those of controls. Fasting leptin levels in CF were
      significantly higher in CF patients (p=0.030), compared to controls and
      significantly lower in CF males as compared to CF females (p=0.01). Fasting
      ghrelin levels were significantly lower in CF males as compared to male controls
      (p<0.001) and comparable in females. CONCLUSIONS: As the overall clinical outcome
      of CF patients is related to the nutritional status and body weight, the role of
      ghrelin and leptin in these patients needs to be elucidated.

PMID- 17196449
TI  - Electrospray ionization LC-MS/MS validated method to quantify griseofulvin in
      human plasma and its application to bioequivalence study.
AB  - A simple, sensitive and rapid liquid chromatography/tandem mass spectrometry (LC
      MS/MS) method has been developed and validated to quantify griseofulvin in human
      plasma using propranolol hydrochloride as internal standard (IS). Samples were
      prepared using solid phase extraction and analysed without drying and
      reconstitution. The analytes were chromatographed on Hypersil, hypurity C18
      reverse phase column under isocratic conditions using 0.05% formic acid in
      water:acetonitrile (30:70, v/v) as the mobile phase. Total chromatographic run
      time was 3.0 min. Quantitation was done on a triple quadrupole mass analyzer API
      3000, equipped with turbo ion spray interface and operating in multiple reaction
      monitoring (MRM) mode to detect parent-->product ion transition for analyte and
      IS. The method was validated for sensitivity, matrix effect, accuracy and
      precision, linearity, recovery and stability studies. Linearity in plasma was
      observed over the concentration range 20-3000 ng/mL for griseofulvin. Lower limit
      of quantification (LLOQ) achieved was 20 ng/mL with precision (CV) less than 10%
      using 5 microL injection volume. The absolute recovery of analyte (87.36%) and IS
      (98.91%) from spiked plasma samples was consistent and reproducible. Inter-batch
      and intra-batch coefficients of variation across four validation runs (LLOQ, LQC,
      MQC and HQC) was less than 7.5%. The accuracy determined at these levels was
      within +/-4.2% in terms of relative error. The method was applied to a pilot
      bioequivalence study of 500 mg griseofulvin tablet in six healthy human subjects
      under fed condition.

PMID- 17196450
TI  - Carditis is related to Helicobacter pylori infection in dyspeptic children and
      adolescents.
AB  - BACKGROUND: Etiology of gastric cardia inflammation is still controversial. AIMS:
      To evaluate the association between carditis and Helicobacter pylori infection
      and the correlation among inflammatory changes observed in biopsies taken from
      cardia, corpus, and antrum in a well-defined group of patients. PATIENTS: The
      mean age of 45 dyspeptic patients was 10.4 years (range 5.1-17.0 years); gender
      F/M rate: 1.6/1. METHODS: A total of 450 specimens from esophagus (2), cardia
      (2), corpus (3), and antrum (4) were collected for biopsy. The presence of H.
      pylori was assessed by histology and a rapid urease test. The types of glandular
      epithelium of cardia found in specimens were identified and both inflammatory
      changes and H. pylori density were graded. RESULTS: Carditis was present in
      specimens of 30/45 (66.7%) of the patients. Presence of H. pylori in specimens
      was detected in the antrum (26/45; 57.8%), in the corpus (19/45; 42.2%), and in
      the cardia (14/45; 31.1%). There was a strong association between carditis and
      presence of H. pylori infection (OR=27.08) by multivariate analysis. The scores
      for inflammation and activity in the cardia, corpus and antrum have shown a
      relationship except for both cardia and antrum H. pylori density and corpus and
      cardia activity. The intensity of gastritis and degree of colonization with H.
      pylori were significantly higher in the antrum than in both the corpus and the
      cardia. Pangastritis was highly associated to H. pylori infection in 22/25 (88%)
      of the patients. CONCLUSIONS: 1. Carditis is associated to H. pylori infection in
      children with symptoms of dyspepsia; 2. The degrees of gastritis found at the
      cardia were correlated to those at the antrum and body except for both cardia and
      antrum H. pylori density and corpus and cardia activity.

PMID- 17196451
TI  - The impact of capsule endoscopy on Crohn's disease.

PMID- 17196452
TI  - Risk factors for coronary artery disease in patients with elevated high-density
      lipoprotein cholesterol.
AB  - High high-density lipoprotein (HDL) levels protect against coronary artery
      disease (CAD) development. We hypothesized that patients with CAD and high HDL
      levels would have higher prevalence of other CAD risk factors compared with
      patients with CAD and normal HDL. We identified 41,982 patients from a single
      center with normal levels (40 to 60 mg/dl in men, 50 to 70 mg/dl in women) or
      high HDL levels (> or =70 mg/dl in men, > or =80 mg/dl in women) when last
      measured between January 2000 and April 2004. From this overall population, we
      characterized a cohort of 1,610 patients with CAD, including 98 patients with
      high HDL levels. We measured prevalence of traditional CAD risk factors by
      comparing these 98 patients with patients with CAD and normal HDL levels (n =
      1,512). We performed manual chart review in patients (n = 196) matched 1:1 by
      age, gender, and HDL level to obtain further detail with regard to differences in
      family history and lifestyle factors. In patients with CAD, those with high HDL
      levels (98 of 1,610, 6.1%) were of similar age (71.1 vs 69.6 years, p = 0.23),
      had similar prevalence of hypertension (78.6% vs 88.7%, p = 0.30), lower levels
      of low-density lipoprotein (85.3 vs 90.9 mg/dl, p = 0.04) and triglycerides (87.1
      vs 141.2 mg/dl, p <0.01), and a lower prevalence of diabetes (28.6% vs 38.4%, p =
      0.05) compared with patients with normal HDL levels. In logistic regression
      models, patients with high HDL levels and CAD were less likely to have diabetes
      (adjusted odds ratio 0.60, 95% confidence interval 0.38 to 0.95, p = 0.03) or
      obesity (adjusted odds ratio 0.50, 95% confidence interval 0.25 to 0.99, p =
      0.046) than patients with normal HDL levels and CAD. In conclusion, patients with
      high HDL and CAD had a similar or lower prevalence of traditional CAD risk
      factors compared with patients with normal HDL levels and CAD.

PMID- 17196453
TI  - Meta-analysis of the studies assessing temporal changes in coronary plaque volume
      using intravascular ultrasound.
AB  - To assess the temporal effect of statin therapy on coronary atherosclerotic
      plaque volume measured by intravascular ultrasound (IVUS), we searched PubMed for
      eligible studies published between 1990 and January 2006. Inclusion criteria for
      retrieved studies were (1) IVUS volume analysis at baseline and follow-up and (2)
      statin therapy in > or =1 group of patients. All data of interest were abstracted
      in prespecified structured collection forms. Statistical analysis was performed
      with Review Manager 4.2. Random-effect weighted mean difference (WMD) was used as
      summary statistics for comparison of continuous variables. Nine studies of 985
      patients (with 11 statin treatment arms) were selected. After a mean follow-up of
      9.8 +/- 4.9 months, we found a significant decrease in coronary plaque volume
      (WMD -5.77 mm(3), 95% confidence interval -10.36 to -1.17, p = 0.01), with no
      significant heterogeneity across studies (p = 0.47). Prespecified subgroup
      analyses showed similar trends. Studies in which the achieved low-density
      lipoprotein (LDL) cholesterol level was <100 mg/dl showed a trend for plaque
      regression (WMD -7.88 mm(3), 95% confidence interval -16.31 to 0.55, p = 0.07),
      whereas studies in which the achieved level of LDL cholesterol was > or =100
      mg/dl, the trend was less evident (WMD -4.22 mm(3), 95% confidence interval 
      10.27 to 1.82, p = 0.17). Plaque volume remained essentially unchanged in
      patients not treated with statins (WMD 0.13 mm(3), 95% confidence interval -4.42
      to 4.68, p = 0.96). In conclusion, statin therapy, particularly when achieving
      the target LDL level, appears to promote a significant regression of coronary
      plaque volume as measured by IVUS.

PMID- 17196454
TI  - Gender comparison of efficacy and safety of ranolazine for chronic angina
      pectoris in four randomized clinical trials.
AB  - More women than men with myocardial infarction have previous stable angina
      pectoris. Women also have an increased incidence of angina after percutaneous
      coronary intervention and coronary artery bypass grafting. Data from 1,737
      patients with stable angina pectoris in 4 international trials (Monotherapy
      Assessment of Ranolazine In Stable Angina [MARISA], Combination Assessment of
      Ranolazine In Stable Angina [CARISA], Ranolazine Versus Atenolol Comparison in
      Chronic Angina [RAN080], and Efficacy of Ranolazine in Chronic Angina [ERICA])
      were used to compare efficacy and safety of ranolazine therapy for angina in
      women and men. MARISA, CARISA, and RAN080 included exercise testing; CARISA,
      RAN080, and ERICA assessed angina frequency and nitroglycerin consumption; and
      ERICA included quality-of-life assessment using the Seattle Angina Questionnaire.
      MARISA, CARISA, and ERICA used the extended-release formulation of ranolazine;
      RAN080 used ranolazine immediate release. All 4 studies showed overall efficacy
      and safety of ranolazine. In subgroup analyses, women showed less improvement
      than men in exercise testing. However, similar improvements for women and men
      were noted in angina frequency and nitroglycerin consumption, and in ERICA, in
      the angina frequency dimension of the Seattle Angina Questionnaire. In
      conclusion, explanations for the gender treatment differences for exercise
      parameters but comparable effects on decrease in angina frequency and
      nitroglycerin use are uncertain, but may include differences in patient
      demographics, reasons for stopping exercise, and type of exercise protocol used.

PMID- 17196455
TI  - Partial inhibition of platelet thromboxane A2 synthesis by aspirin is associated
      with myonecrosis in patients with ST-segment elevation myocardial infarction.
AB  - Heterogeneity in response to aspirin (ASA) treatment, or "aspirin resistance,"
      could be of importance in patients with ST-segment elevation myocardial
      infarction (STEMI). Decreased effects of ASA in platelets could be due to partial
      inhibition of cyclo-oxygenase-1 (COX-1) or to COX-1-independent mechanisms. We
      evaluated the effect of ASA treatment in patients with STEMI for (1) platelet
      thromboxane A(2) (TXA(2)) synthesis, (2) platelet recruitment elicited by TXA(2)
      dependent and -independent mechanisms, and (3) a possible association of these
      aspects of platelet reactivity with serum markers of myonecrosis. We studied 62
      ASA-treated patients within 48 hours of onset of the acute event and 69 ASA-free
      and 10 ASA-treated controls. TXA(2) synthesis and platelet recruitment (fluid
      phase proaggregate activity of cell-free releasate) were assessed after collagen
      stimulation (1 micro g/ml) of whole blood. Partial inhibition of TXA(2) by ASA
      was found in 21 patients (34%). This was associated with significant increases in
      troponin T, creatine kinase-MB mass, creatine kinase, and recruiting activity
      versus 41 patients with blocked TXA(2) production. This was independent of
      fibrinolysis, and platelet COX-2 expression was not augmented. TXA(2) blockade
      was achieved after subsequent daily treatments or platelet incubation with ASA in
      vitro, suggesting lower sensitivity of COX-1 to ASA. In addition, 28 patients
      (45%) had an abnormally increased recruiting activity despite TXA(2) blockade,
      which was also associated with increased myonecrosis. In conclusion, ASA
      resistance, elicited by TXA(2)-dependent and TXA(2)-independent mechanisms, was
      prevalent in patients with STEMI. This study describes, for the first time, the
      association of partial platelet TXA(2) inhibition with myonecrosis.

PMID- 17196456
TI  - Impact of obstructive sleep apnea on clinical and angiographic outcomes following
      percutaneous coronary intervention in patients with acute coronary syndrome.
AB  - There has been growing evidence associating obstructive sleep apnea (OSA) with
      cardiovascular pathogenesis. We hypothesized that OSA may affect outcomes after
      percutaneous coronary intervention (PCI) in patients with acute coronary syndrome
      (ACS). We performed a sleep study in 89 consecutive patients with ACS who were
      successfully treated with PCI. Patients with an apnea hypopnea index > or
      =10/hour were considered to have OSA. Co-morbidity of OSA with ACS was found in
      51 patients (57%). There were no differences in baseline demographics between
      patients with and without OSA, except for significantly higher high-sensitivity C
      reactive protein levels (0.59 +/- 0.75 vs 0.29 +/- 0.20 mg/dl, p = 0.019) in
      patients with OSA. Patients were followed for a mean period of 227 days. The
      incidence of major adverse cardiac events (cardiac death, reinfarction, and
      target vessel revascularization) was significantly higher in patients with OSA
      (23.5% vs 5.3%, p = 0.022). By multivariate analysis, the presence of OSA was an
      independent predictor for major adverse cardiac events (hazard ratio 11.61, 95%
      confidence interval 2.17 to 62.24, p = 0.004). In addition, quantitative coronary
      angiography at 6-month follow-up depicted significantly greater late loss (1.28
      +/- 0.84 vs 0.69 +/- 0.81 mm, p = 0.003) and a higher binary restenosis rate
      (36.5% vs 15.4%, p = 0.026) in patients with OSA compared with those without OSA.
      In conclusion, the present study showed a high prevalence of OSA among patients
      with ACS. Moreover, OSA appeared to be an independent predictor for clinical and
      angiographic outcomes after PCI.

PMID- 17196457
TI  - Long-term prognostic significance of high-sensitivity C-reactive protein before
      and after coronary angioplasty in patients with stable angina pectoris.
AB  - We examined whether an increase in high-sensitivity C-reactive protein (hs-CRP)
      after percutaneous coronary intervention (PCI) predicts long-term prognosis in
      patients with stable angina pectoris. hs-CRP is an inflammatory marker that
      predicts future cardiovascular events in healthy subjects and patients with
      unstable and stable coronary syndromes. Long-term evaluation of pre- and
      postprocedural inflammatory markers has not been widely reported. In particular,
      the effect of the magnitude of increase in hs-CRP after PCI in stable patients is
      unknown. We prospectively analyzed 89 stable patients treated by PCI for stable
      angina pectoris. Patients were recruited between August 1998 and May 1999, and
      the population was followed until August 2005 (mean follow-up 79.5 +/- 10.3
      months). A major adverse cardiac event (MACE) was defined as the occurrence of
      cardiac death, myocardial infarction, or recurrent angina requiring repeat PCI or
      coronary artery bypass grafting. During the follow-up period, 36 patients
      presented with > or =1 MACE. In multivariate analysis, independent predictors of
      the occurrence of MACEs were previous myocardial infarction and a significant
      increase in hs-CRP after PCI (p = 0.004 and 0.003, respectively). A significant
      increase in hs-CRP after PCI was found to be more predictive of MACEs than hs-CRP
      before and after PCI. In conclusion, in stable coronary artery disease,
      inflammation is associated with long-term adverse events, but the magnitude of
      the inflammatory reaction after PCI appears more predictive than the baseline
      value.

PMID- 17196459
TI  - Relation of uric acid levels to presence of coronary artery calcium detected by
      electron beam tomography in men free of symptomatic myocardial ischemia with
      versus without the metabolic syndrome.
AB  - The objective of this study was to evaluate whether uric acid (UA) levels were
      associated with coronary artery calcium (CAC) in white men asymptomatic for
      coronary heart disease. We also evaluated whether this relation was dependent or
      not on the presence of the metabolic syndrome (MS). The study population
      consisted of 371 asymptomatic Brazilian men (48 +/- 7 years of age) who underwent
      a routine evaluation. The average 10-year total risk of coronary heart disease
      calculated by Framingham risk score was 10.8 +/- 7.8%. The age-adjusted
      prevalence of CAC in patients with a high UA level (fourth quartile > or =7.1
      mg/dl, n = 91) was significantly higher than that in those with a normal UA level
      (58% vs 44%, p = 0.02). With respect to age, smoking, physical activity, and
      components of MS-adjusted analyses, a high UA level was independently associated
      with the presence of CAC (p = 0.043) and with increasing levels of CAC (p =
      0.028). Prevalence of MS showed a graded increase according to serum UA values.
      In patients with the MS, after adjusting for age, smoking, physical activity, and
      white blood cell count, high levels of UA were strongly associated with the
      presence of any CAC (odds ratio 3.47, 95% confidence interval 1.26 to 9.53, p =
      0.01) and with increasing levels of CAC (odds ratio 2.74, 95% confidence interval
      1.15 to 6.50, p = 0.02). Conversely, there was no significant association of high
      UA levels in patients without the MS. However, the interaction between high UA
      level and the MS did not achieve statistical significance for the presence of CAC
      (p = 0.11) or higher levels of CAC (p = 0.16). In conclusion, our study suggests
      that, among asymptomatic moderate-risk men, high UA levels were independently
      associated with CAC in subjects with the MS.

PMID- 17196458
TI  - Comparison of effectiveness of coronary artery bypass grafting versus
      percutaneous coronary intervention in patients with ischemic cardiomyopathy.
AB  - The REvascularization in Ischemic HEart Failure Trial (REHEAT) is a
      nonrandomized, case-controlled, prospective study assessing the hypothesis that
      surgical and percutaneous revascularizations in patients with ischemic
      cardiomyopathy are associated with comparable improvement in left ventricular
      ejection fraction (LVEF) and functional status 12 months after myocardial
      revascularization. The study population consisted of 141 patients with LVEFs of
      <40% and angiographically confirmed coronary artery disease. The primary end
      point was improvement in LVEF 12 months after intervention. Secondary end points
      were in-hospital major adverse events, length of hospitalization, exercise
      tolerance of treadmill stress testing after 12 months, 1-year survival, 1-year
      event-free survival, angina, and heart failure severity after 12 months. The case
      controlled study included 55 patients who underwent percutaneous coronary
      intervention (PCI) and 54 who underwent coronary artery bypass grafting (CABG).
      The incidence of 30-day major adverse events was higher in the CABG group (40.7%
      vs 9%, p = 0.0003), whereas duration of hospital stay was shorter in the PCI
      group (6.8 +/- 3.6 vs 9.2 +/- 2.1 days, p = 0.00001). Increase in LVEF was
      comparable after PCI and CABG (6.0 +/- 7.2% vs 4.4 +/- 9.0% p = 0.12). Long-term
      functional status based on treadmill stress testing was better after PCI
      (Student's t test, p = 0.0003) but, according to Canadian Cardiovascular Society
      and New York Heart Association classifications, was similar in the 2 treatment
      arms (Wilcoxon test, p <0.01). Long-term survival was significantly better for
      patients after PCI (Wilcoxon test, p <0.01); however, major adverse event-free
      survival was better after CABG (Cox-Mantel test, p = 0.0013). In conclusion, PCI
      and CABG are associated with comparable improvements in LVEF in patients with
      ischemic cardiomyopathy. PCI offers a better 1-year survival rate than CABG, but
      the incidence of repeat revascularization is lower with CABG.

PMID- 17196460
TI  - Gender differences in circulating endothelial progenitor cell colony-forming
      capacity and migratory activity in middle-aged adults.
AB  - Middle-aged women have a lower prevalence and incidence of cardiovascular events
      compared with men. The mechanisms responsible for this gender-specific difference
      are unclear. Numeric and functional impairments of bone marrow-derived
      circulating endothelial progenitor cells (EPCs) are associated with increased
      cardiovascular and cerebrovascular morbidity and mortality. It is currently
      unknown whether there are gender-related differences in EPC number and function
      in middle-aged adults. We tested the hypothesis that EPCs isolated from middle
      aged women demonstrate greater colony-forming capacity and migratory activity
      compared with men of similar age. Peripheral blood samples were collected from 50
      sedentary adults, 25 men (59 +/- 1 years of age) and 25 women (58 +/- 1 years of
      age). Mononuclear cells were isolated and preplated for 2 days, and nonadherent
      cells were further cultured for 7 days to determine EPC colony-forming units.
      Migratory activity of EPCs was determined using a modified Boyden chamber. The
      number of EPC colony-forming units was significantly higher (approximately 150%)
      in samples collected from women (16 +/- 3) compared with that collected from men
      (7 +/- 1). In addition, EPC migration (relative fluorescent units) was
      approximately 40% greater in women (729 +/- 74) than in men (530 +/- 67). In
      conclusion, these results demonstrate that EPC colony-forming capacity and
      migratory activity are higher in middle-aged women than in men.

PMID- 17196462
TI  - Diagnostic and prognostic value of a type 1 Brugada electrocardiogram at higher
      (third or second) V1 to V2 recording in men with Brugada syndrome.
AB  - To evaluate the diagnostic and prognostic value of an electrocardiogram (ECG)
      recorded at a higher (third or second) intercostal space, 98 men (17 to 76 years
      of age, mean +/- SD 47 +/- 13; with documented ventricular fibrillation [VF] in
      22 and syncope in 32) were categorized into 3 groups; 68 men had a spontaneous
      type 1 ECG in standard leads V(1) and V(2) (S group), 19 had a spontaneous type 1
      ECG only in the higher V(1) and V(2) leads (H group), and 11 had a type 1 ECG
      only after receiving class Ic sodium channel blockers (Ic group). There were no
      significant differences in baseline clinical characteristics, including VF
      episodes, syncope, atrial fibrillation, family history, late potentials, and
      inducibility of VF during electrophysiologic study across the 3 groups. During
      prospective follow-up periods (779 +/- 525, 442 +/- 282, and 573 +/- 382 days,
      respectively), subsequent cardiac events occurred in 11 men (16%) within the S
      group, in 2 men (11%) in the H group, and in 0 men (0%) in the Ic group (p = NS,
      S vs H group). In men with previous episodes of VF, subsequent cardiac events
      occurred in 7 (44%) within the S group and in 2 (50%) in the H group (p = NS). In
      conclusion, men with a spontaneous type 1 Brugada ECG recorded only at higher
      leads V(1) and V(2) showed a prognosis similar to that of men with a type 1 ECG
      in using standard leads V(1) and V(2).

PMID- 17196461
TI  - Frequency of interatrial block in patients with sinus rhythm hospitalized for
      stroke and comparison to those without interatrial block.
AB  - Interatrial block (IAB; P wave > or =110 ms) is a potent correlate of left atrial
      (LA) enlargement and electromechanical dysfunction and a strong predictor of
      atrial tachyarrhythmias, in particular, atrial fibrillation. Although these
      associations increase its risk for embolism, i.e., cardioembolic stroke, such a
      phenomenon has been inadequately investigated. We investigated 85 general
      hospital patients who had been admitted to the neurologic unit between January
      2003 and December 2004 for embolic stroke. Of those, 66 patients who had
      electrocardiograms that showed sinus rhythm were evaluated for IAB and
      categorized as those with IAB and those without (controls). Medical records were
      then reviewed for common co-morbidities and stroke risk factors, high-resolution
      carotid artery Doppler ultrasonographic study reports, and 2-dimensional
      echocardiograms obtained during the current admission for embolic stroke; 40
      patients (61%) had IAB. There was a 55% prevalence of LA enlargement (diameter in
      the parasternal long-axis view > or =40 mm, p <0.001). LA thrombi and/or
      spontaneous contrast ("smoke") were noted on echocardiograms in 6 patients with
      IAB (15%) but not in any of the controls (p = 0.038). Five of those 6 patients
      with such LA thrombi had dilated LA cavities. In conclusion, IAB could be a risk
      for embolic stroke due to its known sequelae of LA dilation and electromechanical
      dysfunction that predispose to thrombosis. If prospective studies prove this to
      be so, the need for anticoagulation use in such patients should be investigated.

PMID- 17196463
TI  - Angiographic localization of potential culprit coronary arteries in patients with
      interatrial block following a positive exercise tolerance test.
AB  - Interatrial block (IAB), denoted by P waves > or =110 ms, is believed to be
      associated with underlying ischemia, particularly with that of its principal
      interatrial conduction pathway, the Bachmann bundle. We investigated if there is
      an angiographic association of IAB on electrocardiograms at rest in patients who
      underwent cardiac angiography after a positive exercise tolerance test (ETT)
      result. Twenty-seven patients with IAB and 42 control patients without IAB on
      electrocardiograms at rest who had evidence of ischemia on cardiac angiography
      after ETT were identified. Coronary vessels that were angiographically most
      significantly stenosed (> or =70% occlusion indicating stenosis) were noted for
      statistical comparison (a p value <0.05 was considered statistically
      significant). Among patients with IAB, the right coronary artery was the
      predominant vessel to be affected, with > or =70% narrowing compared with the
      left, inclusive of the left main, left circumflex, obtuse marginal, and diagonal
      coronary arteries (58% vs 23%, p = 0.03). Right coronary artery lesions in
      patients with IAB were mostly in the proximal and mid portions (54% vs 25% for
      the entire left coronary artery, p = 0.02). No such difference was noted in
      control subjects. In conclusion, in patients with IAB at rest who have coronary
      heart disease, the right coronary artery is predominantly more significantly
      affected.

PMID- 17196465
TI  - Relative merits of M-mode echocardiography and tissue Doppler imaging for
      prediction of response to cardiac resynchronization therapy in patients with
      heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
AB  - M-mode echocardiography (using the septal-to-posterior wall motion delay [SPWMD])
      and color-coded tissue Doppler imaging (TDI; using the septal-to-lateral delay in
      peak systolic velocity) have been proposed for assessment of left ventricular
      (LV) dyssynchrony and prediction of response to cardiac resynchronization therapy
      (CRT). In this study, a head-to-head comparison between M-mode echocardiography
      and color-coded TDI was performed for assessment of LV dyssynchrony and
      prediction of response to CRT. Consecutive (n = 98) patients with severe heart
      failure (New York Heart Association class III/IV), LV ejection fraction < or
      =35%, and QRS duration >120 ms underwent CRT. Before pacemaker implantation, LV
      dyssynchrony was assessed by M-mode echocardiography (SPWMD) and color-coded TDI
      (septal-to-lateral delay). At baseline and 6 months after implantation, clinical
      and echocardiographic parameters were evaluated. SPWMD measurement was not
      feasible in 41% of patients due to akinesia of the septal and/or posterior walls
      or poor acoustic windows. Conversely, the septal-to-lateral delay could be
      assessed in 96% of patients. At 6-month follow-up, 75 patients (77%) were
      classified as responders to CRT (improvement > or =1 New York Heart Association
      class). The sensitivity and specificity of SPWMD were lower compared with those
      of septal-to-lateral delay (66% vs 90%, p <0.05; 50% vs 82%, p = NS,
      respectively). In conclusion, LV dyssynchrony assessment was feasible in 59% of
      patients with M-mode echocardiography compared with 96% (p <0.05) when color
      coded TDI was used. Color-coded TDI was superior to M-mode echocardiography for
      prediction of response to CRT.

PMID- 17196464
TI  - Contribution of right-sided heart enlargement to cardiomegaly on chest
      roentgenogram in diastolic and systolic heart failure.
AB  - We investigated the contribution of a dilated right-sided heart to
      roentgenographic cardiomegaly in patients with heart failure (HF) and a normal
      ejection fraction (EF; diastolic HF) and those with HF and a decreased EF
      (systolic HF). We compared the cardiothoracic ratio (CTR) on upright chest
      roentgenograms and major- and minor-axis dimensions of the 4 cardiac chambers on
      echocardiograms in patients with HF and a normal EF (> or =0.50, n = 35) and
      those with a decreased EF (<0.50, n = 37) and examined the correlation between
      the CTR and cardiac chamber dimensions. The CTR did not differ between patients
      with normal and decreased EF values (0.58 +/- 0.07 vs 0.60 +/- 0.06, p = 0.26).
      Left-side cardiac chamber dimensions were substantially smaller in patients with
      a normal EF than in those with a decreased EF (left ventricular minor-axis
      dimension, 4.4 +/- 0.7 vs 5.8 +/- 0.8 cm, p <0.001). In contrast, right-side
      cardiac chamber dimensions were generally similar between groups. The CTR
      correlated with major-axis dimensions of the right ventricle and right atrium (p
      <0.01 for the 2 comparisons), but not with the left-side cardiac chamber
      dimensions (all p values >0.05). In conclusion, the CTR predominantly reflects
      right- rather than left-sided heart size in patients with HF. Right-sided heart
      size is similar between patients with normal and decreased EF values. Thus,
      despite the substantial difference in left ventricular size and EF, there is
      substantial overlap in the CTR between patients with diastolic and systolic HFs
      and the CTR is unable to discriminate between groups.

PMID- 17196466
TI  - Relation of isovolumic times after cardiac resynchronization therapy to
      improvement in exercise capacity.
AB  - Isovolumic times (IVTs) comprise a determinant of exercise capacity in
      cardiomyopathy. We postulated that an increase in exercise capacity after cardiac
      resynchronization therapy (CRT) might be related to a more efficient cardiac
      cycle due to decreasing IVTs and increased filling times. According to standard
      selection criteria, a CRT device was implanted in 52 patients (37 men; 69 +/- 8
      years) with a QRS duration of 174 +/- 30 ms. The etiology was ischemic in 22 and
      idiopathic in 30 patients. A 6-minute walking test (MWT) and echocardiographic
      Doppler were performed before and 3 and 6 months after CRT. Timing cycles were
      obtained with echocardiographic Doppler. An improvement in MWT by >15%
      (responders) after 6 months of CRT was observed in 46% of patients. The MWT was
      moderately correlated with baseline time intervals (IVT r = -0.44, filling time r
      = 0.52), but not to baseline left ventricular ejection fraction (r = -0.06).
      However, change in the MWT after 3 and 6 months was best related to changes in
      IVT (r = -0.66 and -0.68, respectively). Receiver-operating characteristic curve
      analysis of baseline IVT showed that an IVT >29% predicted exercise response with
      a positive predictive value of 89% and a negative predictive value of 77%. In
      conclusion, improvement in exercise tolerance after CRT is associated with a
      decrease in prolonged IVT. Baseline IVT might be used as an adjunctive parameter
      for selecting symptomatic responders to CRT.

PMID- 17196467
TI  - Intra- and interatrial asynchrony in patients with heart failure.
AB  - Heart failure (HF) is associated with atrial conduction delay. Color tissue
      Doppler imaging was used to evaluate intra- and interatrial asynchrony in
      patients with HF, patients with structural heart disease without HF, and
      controls. Twenty-three controls (mean age 65 +/- 13 years), 29 patients with
      structural heart disease without HF (mean age 68 +/- 9 years), and 29 patients
      with HF (mean age 67 +/- 9 years) were studied. Patients had no histories of
      atrial fibrillation. Echocardiographic color tissue Doppler imaging of the atria
      was performed. Measurements below the atrioventricular plane were selected on the
      right atrial (RA) free wall, interatrial septum (IAS), and left atrial (LA) free
      wall. The time difference from the onset of the P wave to the onset of the A wave
      at the right atrium (P-RA), the IAS (P-IAS), and the left atrium (P-LA) was
      measured. Asynchrony was defined as the differences between P-IAS and P-RA (RA
      asynchrony), P-LA and P-IAS (LA asynchrony), and P-LA and P-RA (interatrial
      asynchrony). In patients with HF, a significant increase in RA asynchrony was
      observed compared with controls and patients without HF (30 +/- 21 vs 12 +/- 13
      and 14 +/- 15 ms, p <0.001). LA asynchrony was not different (19 +/- 26 vs 25 +/-
      13 vs 25 +/- 14 ms, p = NS). Interatrial asynchrony was significantly increased
      in patients with HF (49 +/- 24 vs 37 +/- 9 and 39 +/- 17 ms, p = 0.04). There
      were moderate but significant correlations of RA asynchrony with log N-terminal
      pro-B-type natriuretic peptide (r = 0.3, p = 0.01) and the ejection fraction (r =
      -0.4, p <0.001). In conclusion, in patients with HF, significant RA and
      interatrial asynchrony was documented, evaluated by noninvasive color tissue
      Doppler imaging. Asynchrony was related to N-terminal-pro-B-type natriuretic
      peptide and to the ejection fraction.

PMID- 17196468
TI  - Left ventricular function in normotensive young adults with well-controlled type
      1 diabetes mellitus.
AB  - The aim of this study was to determine whether early myocardial structural and
      functional systolic and diastolic alterations in asymptomatic and uncomplicated
      patients with type 1 diabetes mellitus (DM) could be detected using the new
      highly sensitive echocardiographic techniques of integrated backscatter and color
      Doppler myocardial imaging. Forty asymptomatic and uncomplicated patients with
      type 1 DM and 40 gender- and age-matched normal controls were studied. All
      patients were analyzed by conventional and new echocardiographic techniques
      (integrated backscatter and color Doppler myocardial imaging). Patients with DM
      showed reduced systolic function compared with controls, evidenced by
      significantly lower peak strain, strain rates, and cyclic variation indexes at
      the septum (p <0.0001, <0.01, and <0.001, respectively) and at the posterior wall
      level (p <0.0001, <0.0001, and <0.001, respectively). On receiver-operating
      characteristic curve analysis, systolic strain and the cyclic variation index
      showed the highest discriminating power for separating patients with DM and
      control subjects. Neither structural or ultrastructural nor diastolic functional
      abnormalities were detected. On univariate regression analysis, a significant
      inverse correlation was found for DM duration with conventional (E/A ratio) and
      unconventional (tissue Doppler imaging E/A ratio) indexes of diastolic function,
      in the absence of any correlation for systolic function. In conclusion, highly
      sensitive ultrasonic techniques demonstrate evidence of left ventricular systolic
      dysfunction in the early stage of type 1 DM, in the absence of ultrastructural
      and left ventricular diastolic functional abnormalities.

PMID- 17196469
TI  - Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of
      randomized clinical trials.
AB  - Some nonsteroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2
      selective inhibitors, have been associated with increased cardiovascular (CV)
      events in recent clinical trials or observational studies. To determine whether
      the cyclooxygenase-2 selective inhibitor celecoxib affects CV risk, the incidence
      of CV events was analyzed in patients treated with celecoxib, placebo, or
      nonselective NSAIDs in the clinical trial database for celecoxib using defined
      Antiplatelet Trialists' Collaboration end points of nonfatal myocardial
      infarction, nonfatal stroke, and CV death. Patient data were derived from studies
      in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, low back pain,
      and Alzheimer's disease. This meta-analysis included (1) 7,462 patients exposed
      to celecoxib 200 to 800 mg/day for 1,268 patient-years compared with 4,057
      patients treated with placebo for 585 patient-years, and (2) 19,773 patients
      treated with celecoxib 200 to 800 mg/day for 5,651 patient-years compared with
      13,990 patients treated with nonselective NSAIDs (diclofenac, ibuprofen,
      naproxen, ketoprofen, and loxoprofen) for 4,386 patient-years. CV events were
      adjudicated by a 3-member expert end point committee (WBW, JSB, PBG) blinded to
      treatment group and study. The incidence rates of the combined CV events were not
      significantly different between patients treated with celecoxib and placebo or
      between those treated with celecoxib and nonselective NSAIDs. Event rates were
      similar for adjudicated and nonadjudicated data. Dose of celecoxib, the use of
      aspirin, or the presence of CV risk factors did not alter these results. In
      conclusion, these analyses failed to demonstrate an increased CV risk with
      celecoxib relative to placebo and demonstrated a comparable rate of CV events
      with celecoxib treatment compared with nonselective NSAIDs.

PMID- 17196470
TI  - Association of interleukin-6 and C-reactive protein with subclinical carotid
      atherosclerosis (the Rancho Bernardo Study).
AB  - Studies of interleukin-6 (IL-6) and C-reactive protein (CRP) as predictors of
      atherosclerosis have had mixed results. The purpose of this study was to assess
      the associations of IL-6 and CRP with the severity of subclinical carotid
      atherosclerosis measured 12 years later. Participants were 392 adults (56.9%
      women, mean age 63.2 years) from the Rancho Bernardo Study who had biomarkers
      measured from 1984 to 1987 and carotid intima-media thickness (IMT) measured from
      1996 to 1998. Age-adjusted mean carotid IMT was significantly greater in men than
      women. After adjusting for traditional cardiovascular risk factors, carotid IMT
      increased significantly with increasing IL-6 quartiles (p <0.001). In similar
      analyses, the association between CRP quartiles and carotid IMT was weaker but
      remained statistically significant (p <0.05). In multiple regression analysis, IL
      6 was significantly associated with carotid IMT regardless of CRP. Conversely,
      CRP was significantly associated with carotid IMT when IL-6 was not included in
      the model, but this association became nonsignificant when IL-6 was included. In
      conclusion, baseline IL-6 and CRP were significantly associated with carotid
      atherosclerosis independent of traditional cardiovascular disease risk factors.
      The association of IL-6 was independent of CRP, but not vice versa, suggesting an
      effect of IL-6 on an earlier state of atherosclerosis.

PMID- 17196471
TI  - Possible gender-related differences in the risk-to-benefit ratio of thrombolysis
      for acute submassive pulmonary embolism.
AB  - The indications for thrombolytic treatment in normotensive patients with
      pulmonary embolism (PE) are still the subject of debate, and it also remains
      questionable whether the efficacy and safety of thrombolysis are similar in men
      and women. To address the latter issue, the present study analyzed a large
      population of 428 women and 291 men with acute submassive PE derived from a
      prospective multicenter registry. Initial treatment consisted either of
      thrombolysis (<24 hours after diagnosis) or heparin alone. Thirty-day overall
      mortality was almost identical (11%) in heparin-treated men and women. Early
      thrombolysis was associated with drastically reduced death rates (2.7% vs 11% in
      the heparin group, p = 0.033) in men, whereas the reduction was nonsignificant (p
      = 0.181) in women. Multivariate analysis revealed that early thrombolysis was
      independently associated with reduced mortality rates in men (odds ratio 0.21,
      95% confidence interval 0.05 to 0.96). In comparison, its favorable effect in
      women was marginal (odds ratio 0.77, 95% confidence interval 0.30 to 1.97).
      Gender-specific differences were also observed with regard to the reduction of
      symptomatic PE recurrence (in men, from 21.6% to 8.2%, p = 0.009; in women, from
      16.9% to 8.3%, p = 0.049). In contrast, thrombolysis resulted in a more than
      threefold increase in major bleeding in women (from 8.4% to 27.1%, p <0.001), a
      more pronounced effect than in men (from 6.9% to 15.1%, p = 0.055). In
      conclusion, the present study generated the hypothesis that women with submassive
      PE might benefit less from thrombolytic treatment in terms of survival and PE
      recurrence and that they could be exposed to a higher bleeding risk compared with
      men.

PMID- 17196472
TI  - Frequency and significance of troponin T elevation in acute ischemic stroke.
AB  - Elevated levels of troponin have been reported in patients with acute ischemic
      stroke. In this prospective study, the prevalence and characteristics of troponin
      elevation were examined in 244 patients with acute ischemic stroke but without
      overt ischemic heart disease. Troponin T (TnT) and creatine kinase-MB (CK-MB)
      concentrations were measured and 12-lead electrocardiograms obtained daily during
      the first 5 days of admission. Myocardial perfusion scintigraphy was performed in
      patients with TnT levels of 0.10 micro g/L and in comparable controls without
      elevation of TnT. Patients were followed for a mean of 19 +/- 7 months, with all
      cause mortality as the clinical end point. Elevated levels of TnT (>0.03 micro
      g/L) and creatine kinase-MB (> or =10 micro g/L) were observed in 10% and 9% of
      patients, respectively. Patients with elevated TnT had higher frequencies of
      heart and/or renal failure. Perfusion abnormalities on myocardial perfusion
      scintigraphy at rest were not more frequent or pronounced in patients with TnT
      levels of > or =0.10 micro g/L than in the control group. Only 7 patients (3%)
      had elevations of TnT or creatine kinase-MB and electrocardiographic changes
      suggesting acute myocardial infarctions. According to univariate and multivariate
      analyses, elevation of TnT was significantly associated with mortality. In
      conclusion, elevated levels of TnT are rare in patients presenting with ischemic
      stroke but without overt ischemic heart disease. Heart and renal failure rather
      than myocardial infarction are the most likely causes. When present, elevation of
      TnT seems to be useful in identifying patients who are at increased risk of dying
      within the following 2 years.

PMID- 17196473
TI  - Relation of electrocardiographic criteria for left atrial enlargement to two
      dimensional echocardiographic left atrial volume measurements.
AB  - Left atrial (LA) enlargement by 2-dimensional (2-D) echocardiography predicts
      adverse cardiovascular outcomes. Electrocardiographic (ECG) criteria for LA
      enlargement are based on M-mode echocardiographic LA diameter, which is inferior
      to 2-D-derived LA volumes. This study compared established ECG criteria for LA
      enlargement with atrial volume obtained by 2-D echocardiography to determine if
      traditional ECG criteria accurately represent LA chamber enlargement, therefore
      offering a low-cost screening tool. A total of 261 randomly selected patients who
      underwent electrocardiography and 2-D echocardiography were enrolled. ECG
      parameters and electronically derived P-wave medians were analyzed with
      electronic calipers for maximal accuracy. LA volumes by 2-D echocardiography were
      measured with Simpson's method of discs, with enlargement defined as 32 ml/m(2).
      Sensitivity and specificity tables and receiver-operating characteristic curves
      were constructed for each criterion. Univariate and multivariate analyses were
      performed for predictors of 2-D echocardiographic LA enlargement. LA enlargement
      was present in 43% of patients. ECG P-wave duration was the most sensitive for
      the detection of LA enlargement (69%) but had low specificity (49%). Conversely,
      a biphasic P wave was the most specific (92%) but had low sensitivity (12%). The
      maximum area under the receiver-operating characteristic curve for any criterion
      was 0.64, too low to be of clinical utility. In conclusion, established ECG
      criteria for LA enlargement do not reliably reflect LA enlargement and lack
      sufficient predictive value to be useful clinically. These results suggest that P
      wave abnormalities should be noted as nonspecific LA abnormalities, with the term
      "LA enlargement" no longer used.

PMID- 17196474
TI  - Usefulness of time interval between end of diastolic mitral annular velocity
      pattern and onset of QRS for predicting left ventricular end-diastolic pressure.
AB  - Diastolic mitral annular motion may terminate earlier in patients with higher
      left ventricular end-diastolic pressure (LVEDP). It was therefore hypothesized
      that the time interval measured from the end of the diastolic mitral annular
      velocity pattern to the onset of QRS (the AQ interval) would be a useful
      parameter in predicting LVEDP. The aim of this study was to evaluate the relation
      between the AQ interval and LVEDP. Forty-six patients with suspected coronary
      artery disease who underwent Doppler echocardiographic studies and cardiac
      catheterization were included. LVEDP was determined using a micromanometer-tipped
      catheter. On univariate analysis, the AQ interval had positive correlations with
      the PR interval (r = 0.405, p = 0.005), transmitral E-wave velocity (r = 0.502, p
      <0.001), isovolumic contraction time (r = 0.635, p <0.001), and LVEDP (r = 0.514,
      p <0.001) and a negative correlation with E-wave deceleration time (r = -0.430, p
      = 0.003). After stepwise multiple linear regression analysis, the PR interval,
      transmitral E-wave velocity, and LVEDP were the independent predictors of the AQ
      interval (beta = 0.234, p = 0.033; beta = 0.331, p = 0.004; and beta = 0.350, p =
      0.003, respectively). In conclusion, the AQ interval is a novel, simple, and
      easily obtained index in the prediction of LVEDP.

PMID- 17196475
TI  - Effect of ranitidine on the antiplatelet effects of aspirin in healthy human
      subjects.
AB  - Aspirin is often taken with H2-receptor antagonists. In vitro data suggest that
      certain antagonists, such as ranitidine, have inhibitory effects on platelet
      function. There are no reports on the combined effect of aspirin and H2-receptor
      antagonists on platelet function in humans. Therefore, this study's aim was to
      evaluate the effects of aspirin, ranitidine, and their combination on platelet
      function in humans. Ten healthy men aged 34.7 +/- 2 years received aspirin 325
      mg/day for 4 days followed by a 9-day washout period, 3 days of ranitidine
      treatment (150 mg twice daily), and 4 days of dual-drug treatment. Blood samples
      were drawn at baseline and on the last days of aspirin monotherapy, the washout
      period, ranitidine monotherapy, and dual-drug treatment. Platelet aggregation was
      measured in response to 0.5 mg/ml arachidonic acid, 5 and 10 mumol/L adenosine
      diphosphate, and 1 micro g/ml collagen. The Platelet Function Analyzer 100 test
      was performed, and blood salicylate levels were measured in 6 subjects. Aspirin
      caused a marked reduction in platelet aggregation and prolongation of Platelet
      Function Analyzer 100 closure time. Ranitidine caused a modest decrease in
      platelet aggregation. Unexpectedly, the combination of aspirin and ranitidine
      caused less inhibition of platelet aggregation and prolongation of Platelet
      Function Analyzer 100 time than aspirin alone (p = 0.02 to 0.07 compared with
      aspirin alone). Blood salicylate levels were lower when subjects took aspirin
      with ranitidine than when they took aspirin alone (1 +/- 0.8 vs 1.6 +/- 0.7
      mg/dl, p = 0.005). In conclusion, ranitidine appears to attenuate the
      antiplatelet effects of aspirin in healthy volunteers. The most likely mechanism
      for these findings is a change in the absorption conditions of aspirin in the
      presence of ranitidine.

PMID- 17196476
TI  - Mitral valve prolapse: now you see it; now you don't: recalling the discovery,
      rise and decline of a diagnosis.
AB  - Mitral valve prolapse has been recognized as a clinical entity for only the past
      50 years, although the auscultatory findings of this condition had been
      recognized since the mid-19th century. On the evidence of only a few autopsies,
      it was concluded that the basis for these were pleuropericardial adhesions. Left
      ventricular angiographic studies performed in the 1960s clearly documented the
      true nature of the condition, although it was not until the advent of
      echocardiography that large numbers of patients began to be referred for
      evaluation by this new technique. Because of the wide variety of symptoms in
      patients with suspected mitral valve prolapse, similar to those with other
      conditions, many patients with the latter were referred for evaluation and
      diagnosed with mitral valve prolapse because of misleading M-mode and then 2
      dimensional criteria. It is now recognized, with the use of improved, more
      restrictive echocardiographic criteria, that the prevalence of the disorder is
      much less than previously believed. No test has been devised that will prove 100%
      sensitive and 100% specific for any disorder. In conclusion, this sobering fact
      should encourage the use of all modalities available, including clinical skills,
      to make proper diagnoses when these may be in doubt.

PMID- 17196477
TI  - The editor's roundtable: concurrent hypertension and dyslipidemia.

PMID- 17196478
TI  - Omacor effects on serum lipids and clinical outcome.

PMID- 17196479
TI  - Superiority of contrast echocardiography over conventional echocardiography in
      diagnosing left ventricular hypertrabeculation/noncompaction.

PMID- 17196480
TI  - Levosimendan for the treatment of acute heart failure syndromes: time to identify
      subpopulations of responding patients.

PMID- 17196481
TI  - Omega-3 may indirectly reduce hepatocyte triglycerides through modulation of
      hyperinsulinemia, cytokines and adipocytokines.

PMID- 17196482
TI  - Left ventricular function and response to enalapril in patients with Duchenne
      muscular dystrophy during the second decade of life.

PMID- 17196483
TI  - Clostridium saccharogumia sp. nov. and Lactonifactor longoviformis gen. nov., sp.
      nov., two novel human faecal bacteria involved in the conversion of the dietary
      phytoestrogen secoisolariciresinol diglucoside.
AB  - Two anaerobic bacteria involved in the conversion of the plant lignan
      secoisolariciresinol diglucoside were isolated from faeces of a healthy male
      adult. The first isolate, strain SDG-Mt85-3Db, was a mesophilic strictly
      anaerobic Gram-positive helically coiled rod. Based on 16S r RNA gene sequence
      analysis, its nearest relatives were Clostridium cocleatum (96.7% similarity) and
      Clostridium ramosum (96.6%). In contrast to these species, the isolate was devoid
      of alpha-galactosidase and -glucosidase and did not grow on maltose, melibiose,
      raffinose, rhamnose and trehalose. The hypothesis that strain SDG-Mt85-3Db
      represents a new bacterial species of the Clostridium cluster XVIII was confirmed
      by DNA-DNA hybridisation experiments. The G+C content of DNA of strain SDG-Mt85
      3Db (30.7+/-0.8 mol%) was comparable with that of Clostridium butyricum, the type
      species of the genus Clostridium. The name Clostridium saccharogumia is proposed
      for strain SDG-Mt85-3Db (=DSM 17460T=CCUG 51486T). The second isolate, strain ED
      Mt61/PYG-s6, was a mesophilic strictly anaerobic Gram-positive regular rod. Based
      on 16S rRNA gene sequence analysis, its nearest relatives were Clostridium
      amygdalinum (93.3%), Clostridium saccharolyticum (93.1%) and Ruminococcus
      productus (93.0%). The isolate differed from these species in its ability to
      dehydrogenate enterodiol. It also possessed alpha-arabinosidase and 
      galactosidase and had a higher G+C content of DNA (48.0 mol%). According to these
      findings, it is proposed to create a novel genus, Lactonifactor, and a novel
      species, Lactonifactor longoviformis, to accommodate strain ED-Mt61/PYG-s6. The
      type strain is DSM 17459T (=CCUG 51487T).

PMID- 17196484
TI  - Informed consent for regional anesthesia: what is necessary?

PMID- 17196485
TI  - Epidemics, evolution, and sacroiliac joint pain.

PMID- 17196486
TI  - Disclosure of risks associated with regional anesthesia: a survey of academic
      regional anesthesiologists.
AB  - BACKGROUND AND OBJECTIVES: In view of the relatively few large studies available
      to estimate the rates of complications following regional anesthesia, we aimed to
      identify and quantify the risks that academic regional anesthesiologists and
      regional anesthesia fellows disclose to their patients before performing central
      and peripheral nerve blockade. METHODS: We asked 23 North American regional
      anesthesia fellowship program directors to distribute a questionnaire to the
      regional anesthesiologists and regional anesthesia fellows at their institutions.
      The questionnaire was designed to capture the risks and corresponding incidences
      that are routinely disclosed to patients before performing the most common
      central and peripheral nerve block techniques. RESULTS: The total number of
      respondents was 79 from 12 different institutions. Fifty-eight (74%) respondents
      disclose risks of regional anesthesia in order to allow their patients to make an
      informed choice, whereas 20 (26%) disclose risks for medicolegal reasons. For
      central neural blockade, the most commonly disclosed risks are headache, local
      pain/discomfort, and infection. For peripheral nerve blockade, the most commonly
      disclosed risks are transient neuropathy, local pain/discomfort, and infection.
      For both central and peripheral nerve blockade, the risks most commonly disclosed
      are also those with the highest-reported incidences. CONCLUSIONS: The risks of
      regional anesthesia most commonly disclosed to patients by academic regional
      anesthesiologists and regional anesthesia fellows are benign in nature and occur
      frequently. Severe complications of regional anesthesia are far less commonly
      disclosed. The incidences of severe complications disclosed by academic regional
      anesthesiologists and their fellows can be inconsistent with those cited in the
      contemporary literature.

PMID- 17196487
TI  - An alternate method of radiofrequency neurotomy of the sacroiliac joint: a pilot
      study of the effect on pain, function, and satisfaction.
AB  - BACKGROUND AND OBJECTIVES: The sacroiliac joint (SIJ) can be a source of chronic
      refractory mechanical spine pain. Few previous studies have described
      radiofrequency (RF) sensory denervation of the SIJ; results have been
      inconsistent and technically demanding. This uncontrolled, prospective, cohort
      study evaluates the effects of an innovative method of RF ablation of the
      posterior sensory nerves of the SIJ on pain, analgesic use, disability, and
      satisfaction of patients suffering with chronic mechanical SIJ pain. METHODS:
      Nine subjects with SIJ pain, confirmed by a local anesthetic joint block, were
      studied. Subjects were treated with a series of RF strip lesions performed
      adjacent to the lateral dorsal foraminal aperture plus conventional monopolar
      lesioning at the L5 dorsal ramus. Each subject completed a questionnaire twice
      before and at 1, 3, 6, 9, and 12 months after the procedure. The questionnaire
      evaluated pain intensity and frequency, analgesic intake, disability,
      satisfaction (with current pain level and the RF procedure), and procedure
      complications. Data were analyzed by using linear mixed model analysis. RESULTS:
      After the procedure, significant reductions of back and leg pain frequency and
      severity, analgesic intake, and dissatisfaction with their current level of pain
      occurred. Complications were minimal. Overall, 8 of 9 subjects were satisfied
      with the procedure. CONCLUSIONS: RF sensory ablation of the SIJ using bipolar
      strip lesions is a technically uncomplicated and low-risk procedure. The
      resulting effects on pain, disability, and satisfaction are promising. Further
      evaluation of this technique, including randomized controlled trials, is
      recommended.

PMID- 17196488
TI  - Effect of addition of various doses of fentanyl intrathecally to 0.5% hyperbaric
      bupivacaine on perioperative analgesia and subarachnoid-block characteristics in
      lower abdominal surgery: a dose-response study.
AB  - BACKGROUND: The purpose of this randomized, double-blind, placebo-controlled
      trial is to study the effect of adding various doses of fentanyl to 2.2 mL of
      bupivacaine (0.5% hyperbaric), for spinal anesthetic in non-obstetric population
      undergoing superficial lower abdominal surgery (hernia repair). METHODS: A
      population of 60 patients belonging to ASA classes I and II, scheduled for
      elective inguinal hernia repair, were randomized to receive a spinal anesthetic
      with 2.2 mL of bupivacaine (0.5% hyperbaric) and saline (control group), or
      fentanyl 10, 20, 30, or 40 microg. The volume of injected drug was kept constant
      at 3 mL by adding preservative-free saline for blinding purposes. Subarachnoid
      block characteristics, drug-related side effects, and postoperative analgesia
      requirements were assessed and recorded. RESULTS: Significant improvement in
      quality and duration of analgesia occurred in treatment groups (receiving
      fentanyl and bupivacaine) compared with the control group (saline and
      bupivacaine) (P < .05). However, no improvement in analgesia occurred when the
      dose of fentanyl added was increased from 10 to 20, 30, or 40 microg.
      CONCLUSIONS: The data suggest that in a non-obstetric population receiving spinal
      anesthetic for superficial lower abdominal surgery (hernia repair), addition of
      10 microg fentanyl to bupivacaine 0.5% (hyperbaric) significantly improves the
      quality and duration of analgesia. No further advantage occurs if the dose of
      fentanyl is increased up to 40 mug.

PMID- 17196490
TI  - Epidural catheter placement in neonates: sonoanatomy and feasibility of
      ultrasonographic guidance in term and preterm neonates.
AB  - BACKGROUND: We report the first prospective sonoanatomic study in neonates with
      the aim to perform ultrasonographic-guided epidural catheter placement in this
      age group. METHOD: One hundred forty-five neonates with a body weight < or =4 kg
      (0.53-4 kg) were included in this prospective study. The study was divided into 3
      consecutive parts. In the first part, the neuraxial sonoanatomy of 60 neonates
      was evaluated. In the second part, 50 neonates scheduled for major abdominal
      surgery were enrolled. In this part, the depth of the ligamentum flavum measured
      with ultrasound was matched up to the depth evaluated clinically with the loss-of
      resistance technique. In the third part, ultrasonographic epidural catheter
      placement was performed in 35 neonates weighing between 620 g and 4 kg. RESULTS:
      The ligamentum flavum, the dura mater, and the termination of the spinal cord
      could be identified in all patients. The first part showed a good correlation
      between body weight and depth of the ligamentum flavum. The median termination of
      the spinal cord corresponded to vertebral level L2. The second part confirmed a
      good correlation between depth of the ligamentum flavum evaluated clinically and
      the depth predicted with ultrasound. Finally, real-time ultrasound-guided
      epidural placement was possible in all 35 neonates. CONCLUSION: Ultrasound
      examination of the spinal cord anatomy provides valuable information for epidural
      catheter placement in neonates. Ultrasonography enables a real-time
      identification of the tip of the needle within the epidural space and a
      visualization of the spread of local anesthetic in these patients.

PMID- 17196489
TI  - Medial branch blocks versus pericapsular blocks in selecting patients for
      percutaneous cryodenervation of lumbar facet joints.
AB  - BACKGROUND AND OBJECTIVES: At many institutions, it is not practically feasible
      to perform a series of controlled or placebo-controlled medial branch blocks on
      several facet joints in order to select patients for facet joint rhizotomy. As
      for uncontrolled blocks, there is no proof that medial branch blocks are superior
      to other types of blocks. This study was performed to compare medial branch
      blocks to simple pericapsular blocks for the selection of patients for lumbar
      facet joint cryodenervation. METHODS: Patient selection was based on history,
      imaging, and physical examination. Diagnostic blocks were either medial branch
      blocks or pericapsular blocks. Percutaneous medial branch cryodenervation was
      performed by use of a Lloyd Neurostat 2000. Outcome parameters were low back pain
      (visual analog scale [VAS]), limitation of activity (Macnab), and overall
      satisfaction. A total of 26 patients were recruited, 13 for each group. Follow-up
      was 6 months. RESULTS: Patients who had been selected by medial branch blocks had
      better pain relief than did patients who had been diagnosed by use of
      pericapsular blocks. At 6 weeks and at 3 months after treatment, these results
      reached statistical significance (VAS 2.2 v 4.2, P < .05). CONCLUSIONS: Our
      results suggest that uncontrolled medial branch blocks are superior to
      pericapsular blocks in selecting patients for facet joint cryodenervation, but
      both blocks work. If serial controlled blocks cannot be used, lumbar facet joint
      pain remains a diagnostic dilemma.

PMID- 17196491
TI  - An assessment tool for brachial plexus regional anesthesia performance:
      establishing construct validity and reliability.
AB  - BACKGROUND AND OBJECTIVES: Technical proficiency in regional anesthesia is often
      determined subjectively through in-training evaluations. Objective assessment
      tools improve these evaluations by providing criteria for measurement. However,
      any evaluation instrument needs to be valid and reliable before it is adopted
      into a curriculum. The purpose of this study is to determine the validity and
      reliability of a devised assessment of residents performing an interscalene
      brachial plexus block (ISB). METHODS: In this prospective study, 10 junior
      trainees and 10 senior trainees were videotaped performing an ISB. Junior
      trainees were defined as in their first year of anesthetic training and had
      performed less than 10 ISBs independently. Senior trainees had completed at least
      1 year of anesthesia training and had performed greater than 10 ISBs
      independently. Two blinded expert raters independently evaluated the performance
      of the ISB using a checklist and global rating scale. Construct validity was
      established if the assessments were able to reliably discriminate between
      different levels of training. RESULTS: Senior trainees performed an ISB
      significantly better than junior trainees when assessed using the global rating
      scale (P < .05) and checklist (P < .001). The overall interrater reliability for
      the global rating scores was excellent (r = 0.85, P < .05) and was good for the
      checklist scores (r = 0.74, P < .05). CONCLUSIONS: Both assessment modalities
      were valid, in that they reliably discriminated between different levels of
      training. Objective measures of technical skills are feasible, timely, and
      improve the validity and reliability of competency assessments.

PMID- 17196492
TI  - Hospitalization costs of total knee arthroplasty with a continuous femoral nerve
      block provided only in the hospital versus on an ambulatory basis: a
      retrospective, case-control, cost-minimization analysis.
AB  - BACKGROUND AND OBJECTIVES: After total knee arthroplasty (TKA), hospitalization
      may be shortened by allowing patients to return home with a continuous femoral
      nerve block (CFNB). This study quantified the hospitalization costs for 10 TKA
      patients receiving ambulatory CFNB versus a matched cohort of 10 patients who
      received CFNB only during hospitalization. METHODS: We examined the medical
      records (n = 125) of patients who underwent a unilateral, primary, tricompartment
      TKA with a postoperative CFNB by 1 surgeon at one institution in an 18-month
      period beginning January 2004. Each of the 10 patients discharged home with an
      ambulatory CFNB (cases) was matched with a patient with a hospital-only CFNB
      (controls) for age, gender, body mass index, and health status. Financial data
      were extracted from the hospital microcosting database. RESULTS: Nine patients
      with ambulatory CFNB (cases) were discharged home on postoperative day (POD) 1
      and 1 on POD 4. Of the controls, 3 were discharged home on POD 3, 6 on POD 4, and
      1 on POD 5. The median (range) costs of hospitalization (excluding implant and
      professional fees) was US dollars 5,292 (US dollars 4,326-US dollars 7,929) for
      ambulatory cases compared with US dollars 7,974 (US dollars 6,931-US dollars
      9,979) for inpatient controls (difference = US dollars 2,682, 34% decrease, P <
      .001). The total charges for hospitalization, the implant, and professional fees
      was US dollars 33,646 (US dollars 31,816-US dollars 38,468) for cases compared
      with US dollars 39,100 (US dollars 36,096-US dollars 44,098) for controls
      (difference = US dollars 5,454, 14% decrease, P < .001). CONCLUSIONS: This study
      provides evidence that ambulatory CFNB for selected patients undergoing TKA has
      the potential to reduce hospital length of stay and associated costs and charges.
      However, the current study has significant inherent limitations based on the
      study design. Additional research is required to replicate these results in a
      prospective, randomized, controlled trial and to determine whether any savings
      exceed additional CFNB costs such as from complications, having caregivers
      provide care at home, and additional hospital/health care provider visits.

PMID- 17196494
TI  - Enhancement of proopiomelanocortin gene promoter activity by local anesthetics in
      a pituitary cell line.
AB  - BACKGROUND AND OBJECTIVES: Corticotropin-releasing hormone (CRH) induces gene
      expression of proopiomelanocortin, a precursor protein of adrenocorticotropic
      hormone and beta-endorphin, by elevating intracellular cyclic adenosine 3',5'
      monophosphate (cyclic AMP) level in anterior pituitary cells and immune cells.
      CRH-induced proopiomelanocortin gene expression plays an important role in stress
      responses and is affected by a variety of drugs, but it is not known whether
      local anesthetics can directly affect the gene expression. We hypothesized that
      local anesthetics may directly affect proopiomelanocortin gene expression and can
      modulate production of adrenocorticotropic hormone and beta-endorphin. METHODS:
      The authors used mouse pituitary tumor cells stably transfected with
      approximately 0.7 kilobases of the rat proopiomelanocortin 5' promoter linked
      with the luciferase gene. In the presence or absence of local anesthetics
      (lidocaine, mepivacaine, bupivacaine, and ropivacaine), cells were stimulated by
      CRH or forskolin. After stimulation, proopiomelanocortin gene promoter activity
      was assessed as luciferase activity, and cyclic AMP efflux was measured by enzyme
      immunoassay. RESULTS: CRH- or forskolin-stimulated proopiomelanocortin promoter
      activity was significantly enhanced by local anesthetics. Cyclic AMP efflux
      induced by CRH was not significantly increased by local anesthetics. CONCLUSIONS:
      It was concluded that local anesthetics potentiate the effect of CRH or forskolin
      on proopiomelanocortin promoter activity without changing the intracellular
      cyclic AMP level. It might be possible that transcriptional regulation mediated
      by cyclic AMP is also enhanced by local anesthetics in the other cells.

PMID- 17196493
TI  - Single-injection brachial plexus anesthesia for arteriovenous fistula surgery of
      the forearm: a comparison of infraclavicular coracoid and axillary approach.
AB  - BACKGROUND AND OBJECTIVES: The surgical site for the creation of an arteriovenous
      fistula at the lateral aspect of the distal forearm may be faster and more
      effectively blocked with the infraclavicular coracoid approach than with the
      axillary approach for brachial plexus block. METHODS: Sixty uremic patients
      scheduled for the creation of an arteriovenous fistula at the forearm were
      randomized to receive a single-injection brachial plexus block with 35 to 50 mL
      mepivacaine 0.95% with epinephrine using the infraclavicular coracoid approach
      (IC group) or the perivascular axillary approach (AX group). A distal muscular
      contraction elicited by a nerve stimulator at current <0.5 mA was used in all
      patients. RESULTS: At 30 and 45 minutes, complete loss of sensation was observed
      more often in group IC than AX in the cutaneous distribution of musculocutaneous
      nerve (62% v 30% [P < .05] and 69% v 40%, respectively [P < .05]), but at 60
      minutes the difference was not statistically significant. In other areas,
      analgesia and motor block were achieved at a similar rate. In 3 patients surgery
      could not be performed under the block due to changes in schedule or the use of a
      brachial tourniquet. Patient satisfaction was equally high in both groups.
      CONCLUSIONS: Blockade of the musculocutaneous nerve developed faster with the
      infraclavicular coracoid approach than with the axillary approach. The
      infraclavicular coracoid approach may be preferable in patients scheduled for the
      creation of an arteriovenous fistula at the forearm.

PMID- 17196495
TI  - Falls associated with lower-extremity-nerve blocks: a pilot investigation of
      mechanisms.
AB  - OBJECTIVE: Documented falls after lower-extremity-nerve blocks are rare. We
      believe this paucity of documented falls is the result of underreporting and the
      lack of serious complications resulting from these falls. In addition, the
      mechanism(s) for falls after lower-extremity-nerve blocks has not been
      elucidated. CASE REPORTS: These reports highlight the mechanism of fall in a
      patient with a femoral-nerve block (FNB) and in a patient with a femoral-nerve
      and sciatic-nerve block (FNB/SNB). In addition, we report our findings when
      volunteers underwent FNB, sciatic-nerve block (SNB) and FNB/SNB and were studied
      in a gait-analysis laboratory. CONCLUSIONS: Lower-extremity-nerve blocks result
      in decreased leg stiffness and lateral instability, which may lead to difficulty
      with pivoting maneuvers.

PMID- 17196496
TI  - Uniform distribution of skin-temperature increase after different regional
      anesthesia techniques of the lower extremity.
AB  - BACKGROUND AND OBJECTIVES: Skin-temperature increase is a reliable but late
      indicator of success during regional-anesthesia techniques. The goal of this
      study is to determine the distribution of skin-temperature changes during
      different regional techniques. Does skin temperature increase in the whole area
      innervated by the blocked neural structures or only in certain regions within
      this area with the capability to react preferentially to sympathetic block (i.e.,
      vessel-rich skin)? Although onset time may vary between different regional
      anesthetic techniques, we hypothesized that the distribution of skin warming is
      equal. METHODS: Skin temperature was assessed continuously by infrared
      thermography in 24 patients who received either combined femoral-nerve and
      sciatic-nerve block, epidural anesthesia, or spinal anesthesia. RESULTS: Apart
      from differences in time of onset, no differential spatial distribution of skin
      temperature changes could be detected. The earliest and greatest rise of skin
      temperature occurred at the great toe (10.6 degrees C +/- 0.4 degrees C), became
      smaller proximally, and was negligible above the ankles, irrespective of the type
      and extent of block. Video-thermography revealed that cold blood flows through
      subcutaneous veins immediately after onset of sympathetic block and initially
      decreases skin temperature (0.6 degrees C +/- 0.3 degrees C) during onset of
      spinal anesthesia. CONCLUSION: Irrespective of the applied regional-anesthetic
      technique, skin-temperature changes are more pronounced distally. Thermography
      prevents false measurements of skin temperature above subcutaneous veins and
      displays flow of cold blood as the mechanism of initial skin-temperature drop
      after regional anesthesia. Measurements of skin-temperature increase cannot be
      used to evaluate the extent of analgesia or sympathetic block.

PMID- 17196498
TI  - Facilitating needle alignment in-plane to an ultrasound beam using a portable
      laser unit.
AB  - OBJECTIVE: Ultrasound guidance can increase success with peripheral nerve blocks.
      Accurate anesthetic injection is optimized with both clear visualization and fine
      adjustment of the needle tip at the target area. Good needle alignment with the
      ultrasound beam and using a freehand technique are both desirable for these
      conditions. The purpose of this report is to describe how a unique, in-plane
      laser guide may be used to improve the alignment of injection needles with
      ultrasound beams in order to promote best needle tip visualization. ILLUSTRATION
      IMAGES: By using a small, battery-operated laser unit mounted onto an ultrasound
      transducer, a method to align the ultrasound scanning plane and laser-line
      projection plane was developed. Such alignment was further demonstrated and
      illustrated in a water bath model. Ultrasound was then used to show how clearly
      the needle shaft and tip can be visualized after needle alignment to the
      ultrasound beam using the laser line shining on the shaft of the needle.
      CONCLUSION: This in vitro demonstration describes the potential use of a readily
      available laser-line unit to assist with in-plane needle alignment with the
      ultrasound plane in order to ultimately improve needle visibility during
      ultrasound-guided peripheral nerve block. It requires minimum specialized
      training and may allow for maximum flexibility with freehand needle insertions in
      a sterile fashion.

PMID- 17196497
TI  - Review of brachial plexus anatomy as seen on diagnostic imaging: clinical
      correlation with computed tomography-guided brachial plexus block.

PMID- 17196500
TI  - Lateral popliteal sciatic-nerve block made easy.

PMID- 17196499
TI  - A typical low-back pain caused by an atypical etiology.
AB  - OBJECTIVE: Pain arising in the lumbar spine can have many etiologies, nearly 80%
      of which cannot be established with certainty. We present a very rare cause of
      back pain. CASE REPORT: A 54-year-old woman presented with a 2-month history of
      low-back pain and right-sided sciatica. Conventional analgesics, physiotherapy,
      and epidural steroid application had failed to provide relief. She had tenderness
      of the right sacroiliac joint. Diagnostic fluoroscopic-guided sacroiliac-joint
      injection with lidocaine did not produce symptomatic relief. Pelvic
      ultrasonography and magnetic resonance imaging showed septated multilocular
      hydatic cysts along the sciatic nerve. Surgical exploration noted multicystic
      lesions along the sciatic nerve woven to the nerve. Her low-back pain disappeared
      completely after the operation. She received oral albendazole for 6 months to
      prevent any recurrence of the disease and remains asymptomatic. CONCLUSION:
      Hydatid cyst can be included in the differential diagnosis of lumbar back pain,
      especially in the endemic areas.

PMID- 17196501
TI  - Ultrasound guidance for brachial plexus localization and catheter insertion after
      complete forearm amputation.

PMID- 17196503
TI  - Screening: seeking a balance.

PMID- 17196502
TI  - Eight ball, corner pocket: the optimal needle position for ultrasound-guided
      supraclavicular block.

PMID- 17196504
TI  - Combination of chemotherapy and immunotherapy for cancer: a paradigm revisited.

PMID- 17196505
TI  - Effect of finasteride on prostate-specific antigen.

PMID- 17196506
TI  - Hormones and genetics caught in the crossfire of preventive medicine.

PMID- 17196507
TI  - Effect of 1 mg/day finasteride on concentrations of serum prostate-specific
      antigen in men with androgenic alopecia: a randomised controlled trial.
AB  - BACKGROUND: Use of 5 mg/day finasteride (Proscar) for benign prostatic
      hyperplasia is known to affect serum concentrations of prostate-specific antigen
      (PSA). When men taking this treatment undergo screening for prostate cancer, a
      compensatory adjustment of the PSA concentration (to multiply the value by two)
      is recommended. Whether this recommendation should apply to men taking 1 mg/day
      finasteride (Propecia) for the treatment of androgenic alopecia is unknown. We
      aimed to assess the effect of 1 mg/day finasteride on serum PSA in men aged 40-60
      years with male-pattern hair loss. METHODS: Between March 13, 1998, and Jan 12,
      2000, 355 men aged 40-60 years with male-pattern hair loss were stratified by age
      decade (40-49 years and 50-60 years), and randomised in a ratio of four to one to
      1 mg/day finasteride or placebo. The primary endpoint was the effect of this
      treatment for 48 weeks on serum PSA concentration compared with placebo. This
      trial is in the process of being registered on the US National Institutes of
      Health website . Analyses were according to protocol. FINDINGS: Within 48 weeks
      of randomisation, men aged 40-49 years and 50-60 years who were assigned 1 mg/day
      finasteride had a median decrease in serum PSA concentration of 40% (95% CI 34
      46) and 50% (44-57), respectively. In men assigned placebo, the median changes
      were 0% [-14 to 14] and a median increase of 13% [2 to 24], respectively.
      INTERPRETATION: In men aged 40-60 years, 1 mg/day finasteride for 48 weeks lowers
      serum PSA concentration. Therefore, the existing recommendation for the
      adjustment of serum PSA concentration in prostate-cancer screening in men taking
      5 mg/day finasteride should also apply to men taking the 1 mg/day preparation for
      male-pattern hair loss. Research is needed to assess the effect of 1 mg/day
      finasteride preparation beyond 48 weeks of treatment.

PMID- 17196509
TI  - Part I: spinal-cord neoplasms-intradural neoplasms.
AB  - Intradural spinal-cord tumours are an uncommon but important consideration in the
      differential diagnosis of patients with back pain, radicular pain, sensorimotor
      deficits, or sphincter dysfunction. Intradural spinal tumours can be divided into
      intramedullary and extramedullary spinal-cord tumours on the basis of their
      anatomical relation to the spinal parenchyma. The heterogeneous cell composition
      of the intradural compartment allows the formation of neoplasms, arising from
      glial cells, neurons, and cells of spinal vasculature. Additionally,
      developmental tumours, metastases, and intradural extension of extradural tumours
      are represented. In this Review, we discuss the published work on intradural
      spinal-cord tumours in terms of epidemiological, radiographic, and histological
      characteristics. Surgical and adjuvant treatment strategies are also reviewed.

PMID- 17196508
TI  - Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2
      mutations: a case-control study.
AB  - BACKGROUND: Several of the known risk factors for ovarian cancer are thought to
      act through their effects on ovulation and the menstrual cycle, such as parity,
      breastfeeding, and use of oral contraceptives. We aimed to assess the effect of
      these three risk factors, and of tubal ligation, on the risk of ovarian cancer in
      women who carry a mutation in the BRCA1 or BRCA2 genes. METHODS: We did a matched
      case-control study in women who were found to carry a pathogenetic mutation in
      BRCA1 or BRCA2. Participants were derived from a population-based study of
      ovarian cancer in Ontario, Canada, and from an international registry of mutation
      carriers based in Toronto, ON, Canada. All participants completed a written
      questionnaire that detailed their reproductive history. Women with invasive
      ovarian cancer and controls were matched on year of birth, country of residence,
      mutation (BRCA1 or BRCA2), and history of breast cancer. The odds ratios and 95%
      CI for ovarian cancer were estimated with respect to use of oral contraceptives,
      parity, breastfeeding, and tubal ligation. FINDINGS: Questionnaires were
      completed by 799 women with a history of invasive ovarian cancer (670 with BRCA1
      mutations, 128 with BRCA2 mutations, and one with a mutation in both genes), and
      controls were 2424 women without ovarian cancer (2043 with BRCA1 mutations, 380
      with BRCA2 mutations, and one with a mutation in both genes). Use of oral
      contraceptives reduced the risk of ovarian cancer in carriers of BRCA1 mutations
      (odds ratio 0.56 [95% CI 0.45-0.71]; p<0.0001) and carriers of BRCA2 mutations
      (0.39 [0.23-0.66]; p=0.0004). Parity was associated with a reduced risk for
      carriers of BRCA1 mutations (0.67 [0.46-0.96]; p=0.03), but with an increased
      risk for those with BRCA2 mutations (2.74 [1.18-6.41]; p=0.02). Breastfeeding was
      associated with a reduced risk for carriers of BRCA1 mutations (0.74 [0.56-0.97];
      p=0.03). An effect of similar magnitude was seen for carriers of BRCA2 mutations
      (0.72 [0.41-1.29]; p=0.27), but this was not statistically significant. The
      association with tubal ligation was not significant for carriers of BRCA1
      mutations (0.80 [0.59-1.08]; p=0.15), or for carriers of BRCA2 mutations (0.63
      [0.34-1.15]; p=0.13). INTERPRETATION: Oral contraceptives could be used as a
      means to prevent ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The
      possible adverse effect of parity on ovarian-cancer risk in women with a BRCA2
      mutation needs further study.

PMID- 17196510
TI  - Management of familial melanoma.
AB  - Relatives of patients with melanoma are at increased risk of melanoma. We review
      the evidence that this risk may be attributed both to shared susceptibility genes
      (both high-penetrance and lower-penetrance genes) and shared environment. The
      most frequent high-penetrance susceptibility gene is CDKN2A, and environmental
      effects on the risk to gene carriers are evident in that CDKN2A penetrance is
      higher in CDKN2A-mutation-positive families living in Australia than those in
      Europe. We review the approaches to managing melanoma families, in which the
      likelihood of there being detectable CDKN2A mutations is positively correlated
      with the number of cases of melanoma in the family. Within families, risk that an
      individual carries a germline mutation can be estimated by pedigree analysis for
      autosomal dominant genes with incomplete penetrance. Prevention advice to
      families relates to moderation of sun exposure and self-examination of naevi,
      although there are few supportive data.

PMID- 17196511
TI  - Primary systemic chemotherapy of invasive lobular carcinoma of the breast.
AB  - Invasive lobular carcinoma is the second most frequent histological type of
      breast cancer and its incidence is increasing. It has unique clinical,
      biological, and molecular features. Invasive lobular carcinoma is almost
      invariably positive for the oestrogen receptor and, when compared with invasive
      ductal carcinoma, it is typically of a lower grade. Even though invasive lobular
      carcinoma represents a distinct clinical entity, the same criteria used for
      invasive ductal carcinoma are currently applied to establish the need for primary
      or adjuvant systemic chemotherapy. We reviewed randomised trials of neoadjuvant
      and adjuvant chemotherapy and noted that insufficient evidence is available to
      support or withhold use of chemotherapy in patients with invasive lobular
      carcinoma. Thus, the benefit from systemic chemotherapy for individuals with this
      form of breast disease is unclear. Invasive lobular carcinoma deserves to be
      investigated separately in prospective clinical trials to define the best
      treatment and prevention strategies.

PMID- 17196512
TI  - Dynamic contrast-enhanced MRI as a predictor of tumour response to radiotherapy.
AB  - A predictive technique in the management of patients with cancer could improve
      the therapeutic index by allowing better individualisation of treatment. The
      standard risk factors that are currently used do not adequately account for the
      unpredictable and substantial variation seen in the treatment response of
      patients with a similar risk profile. Dynamic contrast-enhanced (DCE) MRI is a
      non-invasive technique that can provide anatomical and physiological information
      on the tumour. The DCE-MRI data reflects the tumour microenvironment variables
      that are known to influence radiation response. The aim of this review is to
      describe the potential clinical application of DCE-MRI as a predictor of
      radiation response. We have reviewed the literature and identified 29 studies
      (total of 1194 patients) that correlate DCE-MRI with histopathological or
      clinical outcome data relevant to radiotherapy.

PMID- 17196513
TI  - Teeth: malignant neoplasms in the dental pulp?
AB  - Common pathologies of the dental pulp differentiate between acute and chronic
      inflammatory states caused by caries or dental trauma. Inflammations of the
      dental pulp as a result of neoplastic alterations are generally considered non
      existent. In fact, using the search phrase "dental pulp" combined with "sarcoma",
      "carcinoma", or "neoplasms" in PubMed when using the MeSH search mode yielded no
      reports on primary malignant neoplasms. However, a hand search yields clinical
      reports on pulpal tumours that were published over a century ago. In this Essay,
      the results of a hand search in historic published work are presented.
      Furthermore, deductive reflections are done on general tumour pathogenesis with
      respect to specific anatomical prerequisites of the dental pulp. Because of the
      restricted space in a tooth, tumour expansion will probably lead to the formation
      of irritation dentine by secondary odontoblasts and, subsequently, to a
      haemorrhage infarct of the pulp. One hypothesis states that a purported neoplasm
      of the dental pulp leads to a chronic appositive pulpitis and-sooner or later
      will be treated likewise by root-canal treatment or extraction. Further research,
      including stem-cell studies, is recommended.

PMID- 17196514
TI  - Anhydramnios associated with administration of trastuzumab and paclitaxel for
      metastatic breast cancer during pregnancy.

PMID- 17196515
TI  - Rare and aggressive metastatic, axial multifocal local epithelioid sarcoma
      associated with paraneoplastic granulocytosis and hypoglycaemia.

PMID- 17196516
TI  - Procedure to consistently obtain endothelial and smooth muscle cell cultures from
      umbilical cord vessels.
AB  - The prenatal history of an individual can be responsible to some extent for the
      occurrence of several diseases later in life. Thus, low birth weight has been
      related to an increased risk of developing hypertension or type 2 diabetes. The
      molecular and cellular basis of this increased risk could be found in body fluids
      and cell types that can be obtained just after birth. To get this unique
      information, a methodology was developed to consistently obtain cultures of 4
      cell types, endothelial and smooth muscle cells from both the vein and the
      arteries present in the umbilical cord of an individual. From 21 umbilical cords
      processed, 82 of the 84 possible cell cultures were obtained. The cell cultures
      exhibit the expected cell morphology and cellular characteristics. Thus,
      endothelial cells express the von Willebrand factor, CD31, as well as bind and
      internalize acetylated low-density lipoprotein. Vascular smooth muscle cells
      express the distinctive alpha-actin. Cell cultures can be cryopreserved and grow
      healthy for several passages. No influence of birth weight of the newborn has
      been found in the time required to obtain a primary cell culture for any of the 4
      cell types. In conclusion, the procedure developed allows one to routinely obtain
      actively growing vascular cell cultures that could be used to study the molecular
      and cellular basis of vascular diseases that emerge in adulthood.

PMID- 17196517
TI  - Ethnic differences in plasma levels of interleukin-8 (IL-8) and granulocyte
      colony stimulating factor (G-CSF).
AB  - Ethnic neutropenia is common in people of African descent. As interleukin-8 (IL
      8) and granulocyte colony stimulating factor (G-CSF) bind to receptors on
      neutrophils, ethnic differences in neutrophil counts are hypothesized to result
      in different plasma levels of these cytokines. A prospective study was conducted
      in 72 healthy young volunteers. Neutrophil counts were 60% higher in Caucasians
      (P<0.00001). Average IL-8 and G-CSF levels were about 50% and 70% higher in
      African volunteers compared with Caucasian volunteers (P=0.0008 and P=0.00005,
      respectively). Additionally, oxidative burst capacity in stimulated neutrophils
      was significantly lower in volunteers of African descent (P=0.03 between both
      groups). In sum, lower neutrophil counts are associated with higher levels of IL
      8 and G-CSF in Africans.

PMID- 17196518
TI  - Hypocholesterolemic and antioxidative effects of naringenin and its two
      metabolites in high-cholesterol fed rats.
AB  - This study was conducted to compare the hypocholesterolemic and antioxidant
      effects of naringenin (0.02%), and its metabolites, rho-hyproxyphenylpropionic
      acid (PHPP, 0.012%) and rho-hydroxybenzoic acid (PHB, 0.012%), in 1% cholesterol
      diet-fed rats. All supplements significantly lowered the plasma total-cholesterol
      (total-C), triglyceride (TG) and atherogenic index, and hepatic cholesterol
      levels compared with the control group. The plasma high-density lipoprotein
      cholesterol (HDL-C) concentration was significantly higher in these supplemented
      groups. However, PHB group only affected the reduction of hepatic TG content. The
      hydroxyl-3-methylglutaryl-coenzyme A reductase (HMGR) activity was significantly
      lower in all supplemented groups, whereas only the naringenin group reduced the
      acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity compared with the
      control group. The fecal acidic sterol excretion and hepatic superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) activities were significantly higher in
      all supplemented groups. All supplements also significantly decreased the
      contents of plasma and hepatic thiobarbituric acid reactive substances (TBARS).
      Accordingly, it was considered that naringenin and its metabolites were effective
      on improving the cholesterol and antioxidant metabolism.

PMID- 17196519
TI  - Effect of plant sterols and exercise training on cholesterol absorption and
      synthesis in previously sedentary hypercholesterolemic subjects.
AB  - Plant sterols combined with exercise beneficially alter lipid profiles in
      hypercholesterolemic adults. Although the mechanism by which plant sterols
      favorably modulate lipid levels is well established, no trial to date has
      examined the effect of exercise, alone or combined with plant sterols, on
      cholesterol kinetics. Thus, the current objective was to examine the effects of
      exercise, plant sterols, and the combination of exercise and plant sterols on
      cholesterol absorption and synthesis. In an 8-week, parallel-arm trial, 84
      subjects were randomized to 1 of 4 interventions: plant sterols combined with
      exercise, plant sterols, exercise, or control. Diets were not controlled. Total
      cholesterol and triglyceride levels decreased (P<0.01) by 7.7% and 11.8%,
      respectively, whereas high-density lipoprotein (HDL) cholesterol levels increased
      (P<0.01) by 7.5% in the combination group. Mean posttreatment low-density
      lipoprotein (LDL) cholesterol levels decreased (P<0.01) by 0.30 mmol/L in the
      combination group. Cholesterol absorption was 16% lower (P<0.01) in the
      combination group and 18% lower (P<0.01) in the plant sterol group, when compared
      with control. Exercise had no effect on cholesterol absorption. Nonsignificant
      increases in cholesterol synthesis rates of 63% (0.084+/-0.014 pools/day), 59%
      (0.075+/-0.013 pools/day), and 57% (0.072+/-0.011 pools/day) were observed in the
      combination, exercise, and plant sterol groups, respectively, relative to the
      control group (0.031+/-0.019 pools/day). LDL cholesterol levels correlated with
      cholesterol absorption, as represented by the area under the deuterium enrichment
      curve (r=0.23, P=0.05), and with percent absorption relative to control (r=0.25,
      P=0.03). These findings suggest that exercise does not modulate lipid levels by
      altering to cholesterol absorption or synthesis, whereas plant sterols favorably
      alter levels of LDL cholesterol by suppressing intestinal absorption.

PMID- 17196520
TI  - Prevalence of RHD 1227A and hybrid Rhesus box in the general Chinese population.
AB  - The Rhesus (Rh) blood group is the most polymorphic blood group system.
      Serological analyses revealed that only 0.1% to 0.4% of the Chinese population
      exhibited a D-negative phenotype. In contrast to D-negative Caucasian persons,
      who are mostly associated with a deletion of RHD between the upstream and
      downstream Rhesus boxes, approximately 30% of apparently D-negative Chinese were
      actually DEL, potentially harboring a grossly intact RHD gene. The authors'
      previous detection of the RHD 1227A allele in all DEL samples prompted the
      conclusion that the RHD 1227A gene is highly prevalent in DEL populations of
      Chinese ethnicity, which indicates that it may be a marker for the rapid
      detection of DEL. Currently, random surveys for RHD 1227 A allele and for hybrid
      Rhesus box were conducted among 399 Han Chinese in Taiwan. The estimated
      frequencies of RHD 1227G/G, RHD 1227A/G, RHD A/A, RHD 1227G/-, RHD 1227A/-, and
      RHD-/- were 0.89054, 0.0118, 0.00016, 0.0414, 0.00055, and 0.00192, respectively.
      These results were consistent with the prevalence of D-negative and DEL in
      persons of Chinese ethnicity. The authors conclude that detection of RHD 1227A
      and hybrid Rhesus box alleles is predictive of Rh phenotypes in the Chinese
      population.

PMID- 17196521
TI  - Solvent partition of 14C-unconjugated bilirubin to remove labeled polar
      contaminants.
AB  - Polar derivatives contaminating unconjugated bilirubin (UCB) are customarily
      extracted with weak alkali. As UCB degrades rapidly at alkaline pH, regeneration
      of polar derivatives may limit purification. This problem is especially important
      when trying to eliminate radiolabeled contaminants from 14C-UCB. As polar
      derivatives of UCB should have a much greater aqueous to CHCl3 partition ratio
      (PR) than UCB even at neutral pH, where degradation of UCB is minimal, 14C-UCB in
      CHCl3 was serially extracted with an aqueous buffer at pH 7.0 to determine
      whether labeled derivatives could be preferentially removed. A single extraction
      of customarily purified 14C-UCB removed 0.18+/-0.06% of the radioactivity as
      labeled derivatives. Subsequent serial extractions yielded a stable, 67% lower
      14C-PR with only 0.03% of radioactivity as labeled derivatives. Reverse-phase
      high-performance liquid chromatography (HPLC) of phases from later extractions
      revealed, however, that up to 1.1% of the disintegration per minute (dpm) in
      CHCl3 phases and up to 50% in aqueous phases were polar impurities. HPLC of
      partition phases spiked with purified 14C-UCB revealed that these impurities
      derived from incomplete extraction of the least polar impurities and their
      regeneration during HPLC. In the dark under argon, 14C-UCB in CHCl3or dimethyl
      sulfoxide (DMSO) solution degraded very slowly to polar derivatives. Extraction
      of impurities from a solution of 14C-UCB in CHCl3 is best done using pH 7.0
      buffer, with removal of over 80% of the labeled contaminants remaining after
      customary purification by alkaline extraction.

PMID- 17196522
TI  - Cell-cycle inhibition by TNP-470 in an in vivo model of hepatocarcinoma is
      mediated by a p53 and p21WAF1/CIP1 mechanism.
AB  - The objective of this study was to determine in a rat model of hepatocellular
      carcinoma (HCC) the effects of the antiangiogenic agent TNP-470 on cell
      proliferation and effectors of the apoptotic pathway, including p53,
      p21WAF1/CIP1, cyclin D, and cyclin E. Tumor was induced in male Wistar rats by
      diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene
      administration. Experiments were carried out at 28 weeks after initiating the
      treatment. TNP-470 was administered at 30 mg/kg, 3 times per week from 20 to 28
      weeks. Serum levels of vascular endothelial growth factor (VEGF) and hepatocyte
      growth factor beta (HGFbeta) liver expression were increased by
      hepatocarcinogenesis (+38% and +183%, respectively), and treatment with TNP-470
      was able to prevent the increase in these angiogenic factors induced by HCC. HCC
      coursed with reduced expression of p21WAF1/CIP1 and p53 (-63% and -60%,
      respectively). Hepatic expression of cyclin D and cyclin E were significantly
      increased in rats with HCC (+108% and +115%, respectively). In animals with
      experimental carcinogenesis, a significant increase in the expression of Cdk4 and
      CdK2 was also observed (+119% and +187%, respectively). These effects were
      prevented by TNP-470 administration. In conclusion, cell-cycle inhibition by TNP
      470 is mediated at least in part by an activation of p21WAF1/CIP1 because of a
      p53-dependent mechanism, with reduction of the cyclin D-Cdk4 and cyclin E-Cdk 2
      expression. These cytostatic effects should be considered when assessing the
      efficacy of TNP-470 for anti-angiogenic therapy. These findings may prove useful
      for the development of therapies for the treatment of human HCC.

PMID- 17196523
TI  - High affinity not in the vicinity?
AB  - Functional interactions between the p75 neurotrophin receptor (p75NTR) and the
      Trk receptors were demonstrated several years ago, but their mechanistic basis
      remains uncertain. In this issue of Neuron, Wehrman et al. provide a three
      dimensional structure of the full TrkA ectodomain complexed to NGF and examine
      the possibility of a ternary p75NTR-NGF-TrkA complex.

PMID- 17196524
TI  - The blu Blur: mutation of a vesicular glutamate transporter reduces the
      resolution of zebrafish vision.
AB  - Vesicular transporters mediate the packaging of neurotransmitters into synaptic
      vesicles and can therefore control the amount of neurotransmitter released into
      the synaptic cleft. In this issue of Neuron, Smear et al. demonstrate that
      mutation of a vesicular glutamate transporter (Vglut) found in the retinal
      ganglion cells (RGCs) of zebrafish alters both the synaptic transmission and
      connectivity between RGCs and their targets, limiting the transfer of visually
      evoked activity from RGCs and degrading behaviors that depend on high-acuity
      vision.

PMID- 17196525
TI  - Shopping centers in the brain.
AB  - Knutson et al. performed functional MRI on individuals while the subjects were
      deciding whether or not to purchase various items. Their results, reported in
      this issue of Neuron, support the theory that the decision to purchase involves
      the integration of emotional signals related to the anticipation of both
      obtaining the desired product and suffering the financial loss of paying for it.

PMID- 17196526
TI  - From thought to action: the parietal cortex as a bridge between perception,
      action, and cognition.
AB  - The lateral intraparietal area (LIP) is a subdivision of the inferior parietal
      lobe that has been implicated in the guidance of spatial attention. In a variety
      of tasks, LIP provides a "salience representation" of the external world-a
      topographic visual representation that encodes the locations of salient or
      behaviorally relevant objects. Recent neurophysiological experiments show that
      this salience representation incorporates information about multiple behavioral
      variables-such as a specific motor response, reward, or category membership
      associated with the task-relevant object. This integration occurs in a wide
      variety of tasks, including those requiring eye or limb movements or goal
      directed or nontargeting operant responses. Thus, LIP acts as a multifaceted
      behavioral integrator that binds visuospatial, motor, and cognitive information
      into a topographically organized signal of behavioral salience. By specifying
      attentional priority as a synthesis of multiple task demands, LIP operates at the
      interface of perception, action, and cognition.

PMID- 17196527
TI  - Activity-dependent plasticity of the NMDA-receptor fractional Ca2+ current.
AB  - Ca(2+) influx through NMDA receptors (NMDA-Rs) triggers synaptic plasticity, gene
      transcription, and cytotoxicity, but little is known about the regulation of NMDA
      Rs themselves. We used two-photon glutamate uncaging to activate NMDA-Rs on
      individual dendritic spines in rat CA1 neurons while we measured NMDA-R currents
      at the soma and [Ca(2+)] changes in spines. Low-frequency uncaging trains induced
      Ca(2+)-dependent long-term depression of NMDA-R-mediated synaptic currents.
      Additionally, uncaging trains caused a reduction in the Ca(2+) accumulation per
      unit of NMDA-R current in spines due to a reduction in the fraction of the NMDA-R
      current carried by Ca(2+). Induction of depression of NMDA-R-mediated Ca(2+)
      influx required activation of NR2B-containing receptors. Receptors in single
      spines depressed rapidly in an all-or-none manner. These adaptive changes in NMDA
      R function likely play a critical role in metaplasticity and in stabilizing
      activity levels in neuronal networks with Hebbian synapses.

PMID- 17196528
TI  - Structural and mechanistic insights into nerve growth factor interactions with
      the TrkA and p75 receptors.
AB  - Nerve growth factor engages two structurally distinct transmembrane receptors,
      TrkA and p75, which have been proposed to create a "high-affinity" NGF binding
      site through formation of a ternary TrkA/NGF/p75 complex. To define a structural
      basis for the high-affinity site, we have determined the three-dimensional
      structure of a complete extracellular domain of TrkA complexed with NGF. The
      complex reveals a crab-shaped homodimeric TrkA structure, but a mechanism for p75
      coordination is not obvious. We investigated the heterodimerization of membrane
      bound TrkA and p75, on intact mammalian cells, using a beta-gal protein-protein
      interaction system. We find that NGF dimerizes TrkA and that p75 exists on the
      cell surface as a preformed oligomer that is not dissociated by NGF. We find no
      evidence for a direct TrkA/p75 interaction. We propose that TrkA and p75 likely
      communicate through convergence of downstream signaling pathways and/or shared
      adaptor molecules, rather than through direct extracellular interactions.

PMID- 17196529
TI  - C. elegans G protein regulator RGS-3 controls sensitivity to sensory stimuli.
AB  - Signal transduction through heterotrimeric G proteins is critical for sensory
      response across species. Regulator of G protein signaling (RGS) proteins are
      negative regulators of signal transduction. Herein we describe a role for C.
      elegans RGS-3 in the regulation of sensory behaviors. rgs-3 mutant animals fail
      to respond to intense sensory stimuli but respond normally to low concentrations
      of specific odorants. We find that loss of RGS-3 leads to aberrantly increased G
      protein-coupled calcium signaling but decreased synaptic output, ultimately
      leading to behavioral defects. Thus, rgs-3 responses are restored by decreasing G
      protein-coupled signal transduction, either genetically or by exogenous dopamine,
      by expressing a calcium-binding protein to buffer calcium levels in sensory
      neurons or by enhancing glutamatergic synaptic transmission from sensory neurons.
      Therefore, while RGS proteins generally act to downregulate signaling, loss of a
      specific RGS protein in sensory neurons can lead to defective responses to
      external stimuli.

PMID- 17196530
TI  - Hypoxia enhances S-nitrosylation-mediated NMDA receptor inhibition via a thiol
      oxygen sensor motif.
AB  - Under ambient air conditions, NO inhibits NMDAR activity by reacting with the
      NR2A subunit C399 along with two additional cysteine pairs if their disulfide
      bonds are reduced to free thiol groups [NR1(C744,C798); NR2(C87,C320)]. Here we
      demonstrate that relative hypoxia enhances S-nitrosylation of NMDARs by a unique
      mechanism involving an "NO-reactive oxygen sensor motif" whose determinants
      include C744 and C798 of the NR1 subunit. Redox reactions involving these two
      thiol groups sensitize other NMDAR sites to S-nitrosylation and consequent
      receptor inhibition, while their own nitrosylation has little effect on NMDAR
      activity. The crystal structure of the ligand-binding domain of NR1 reveals a
      flexible disulfide bond (C744-C798), which may account for its susceptibility to
      reduction and subsequent reaction with NO that is observed with biochemical
      techniques. These thiols may be nitrosylated preferentially during increasing
      hypoxia or stroke conditions, thus preventing excessive activity associated with
      cytotoxicity while avoiding blockade of physiologically active NMDARs.

PMID- 17196531
TI  - Vesicular glutamate transport at a central synapse limits the acuity of visual
      perception in zebrafish.
AB  - The neural circuitry that constrains visual acuity in the CNS has not been
      experimentally identified. We show here that zebrafish blumenkohl (blu) mutants
      are impaired in resolving rapid movements and fine spatial detail. The blu gene
      encodes a vesicular glutamate transporter expressed by retinal ganglion cells.
      Mutant retinotectal synapses release less glutamate, per vesicle and per
      terminal, and fatigue more quickly than wild-type in response to high-frequency
      stimulation. In addition, mutant axons arborize more extensively, thus increasing
      the number of synaptic terminals and effectively normalizing the combined input
      to postsynaptic cells in the tectum. This presumably homeostatic response results
      in larger receptive fields of tectal cells and a degradation of the retinotopic
      map. As predicted, mutants have a selective deficit in the capture of small prey
      objects, a behavior dependent on the tectum. Our studies successfully link the
      disruption of a synaptic protein to complex changes in neural circuitry and
      behavior.

PMID- 17196532
TI  - Ca2+ -stimulated adenylyl cyclases regulate ERK-dependent activation of MSK1
      during fear conditioning.
AB  - The cAMP and ERK/MAP kinase (MAPK) signal transduction pathways are critical for
      hippocampus-dependent memory, a process that depends on CREB-mediated
      transcription. However, the extent of crosstalk between these pathways and the
      downstream CREB kinase activated during memory formation has not been elucidated.
      Here we report that PKA, MAPK, and MSK1, a CREB kinase, are coactivated in a
      subset of hippocampal CA1 pyramidal neurons following contextual fear
      conditioning. Activation of PKA, MAPK, MSK1, and CREB is absolutely dependent on
      Ca(2+)-stimulated adenylyl cyclase activity. We conclude that adenylyl cyclase
      activity supports the activation of MAPK, and that MSK1 is the major CREB kinase
      activated during training for contextual memory.

PMID- 17196533
TI  - Grading movement strength by changes in firing intensity versus recruitment of
      spinal interneurons.
AB  - Animals can produce movements of widely varying speed and strength by changing
      the recruitment of motoneurons according to the well-known size principle. Much
      less is known about patterns of recruitment in the spinal interneurons that
      control motoneurons because of the difficulties of monitoring activity
      simultaneously in multiple interneurons of an identified class. Here we use
      electrophysiology in combination with in vivo calcium imaging of groups of
      identified excitatory spinal interneurons in larval zebrafish to explore how they
      are recruited during different forms of the escape response that fish use to
      avoid predators. Our evidence indicates that escape movements are graded largely
      by differences in the level of activity within an active pool of interneurons
      rather than by the recruitment of an inactive subset.

PMID- 17196535
TI  - Responses of trigeminal ganglion neurons during natural whisking behaviors in the
      awake rat.
AB  - Rats use their whiskers to locate and discriminate tactile features of their
      environment. Mechanoreceptors surrounding each whisker encode and transmit
      sensory information from the environment to the brain via afferents whose cell
      bodies lie in the trigeminal ganglion (Vg). These afferents are classified as
      rapidly (RA) or slowly (SA) adapting by their response to stimulation. The
      activity of these cells in the awake behaving rat is yet unknown. Therefore, we
      developed a method to chronically record Vg neurons during natural whisking
      behaviors and found that all cells exhibited (1) no neuronal activity when the
      whiskers were not in motion, (2) increased activity when the rat whisked, with
      activity correlated to whisk frequency, and (3) robust increases in activity when
      the whiskers contacted an object. Moreover, we observed distinct differences in
      the firing rates between RA and SA cells, suggesting that they encode distinct
      aspects of stimuli in the awake rat.

PMID- 17196534
TI  - Sequential use of mushroom body neuron subsets during drosophila odor memory
      processing.
AB  - Drosophila mushroom bodies (MB) are bilaterally symmetric multilobed brain
      structures required for olfactory memory. Previous studies suggested that
      neurotransmission from MB neurons is only required for memory retrieval. Our
      unexpected observation that Dorsal Paired Medial (DPM) neurons, which project
      only to MB neurons, are required during memory storage but not during acquisition
      or retrieval, led us to revisit the role of MB neurons in memory processing. We
      show that neurotransmission from the alpha'beta' subset of MB neurons is required
      to acquire and stabilize aversive and appetitive odor memory, but is dispensable
      during memory retrieval. In contrast, neurotransmission from MB alphabeta neurons
      is only required for memory retrieval. These data suggest a dynamic requirement
      for the different subsets of MB neurons in memory and are consistent with the
      notion that recurrent activity in an MB alpha'beta' neuron-DPM neuron loop is
      required to stabilize memories formed in the MB alphabeta neurons.

PMID- 17196536
TI  - Role of the corpus callosum in speech comprehension: interfacing syntax and
      prosody.
AB  - The role of the corpus callosum (CC) in the interhemispheric interaction of
      prosodic and syntactic information during speech comprehension was investigated
      in patients with lesions in the CC, and in healthy controls. The event-related
      brain potential experiment examined the effect of prosodic phrase structure on
      the processing of a verb whose argument structure matched or did not match the
      prior prosody-induced syntactic structure. While controls showed an N400-like
      effect for prosodically mismatching verb argument structures, thus indicating a
      stable interplay between prosody and syntax, patients with lesions in the
      posterior third of the CC did not show this effect. Because these patients
      displayed a prosody-independent semantic N400 effect, the present data indicate
      that the posterior third of the CC is the crucial neuroanatomical structure for
      the interhemispheric interplay of suprasegmental prosodic information and
      syntactic information.

PMID- 17196538
TI  - Molecular recognition on the supported and on the air/water interface-spread
      protein monolayers.
AB  - Targeting of proteins at interfaces via affinity ligands or specific antibodies
      is important for the understanding of protein functioning in biological
      membranes. This review brings together a great number of research works
      accomplished in this field in the past decade by a variety of analytical methods.
      It highlights two simple in situ techniques of monitoring molecular recognition
      processes at interfaces recently developed in the author's laboratory. The first
      of these techniques is based on the measurements of surface pressure increments
      of a protein monolayer spread at the air/water interface at a constant area
      resulting from the interaction with its specific ligands injected into the
      aqueous subphase beneath the preformed protein monolayer. The second technique
      takes advantage of the feature of [(14)C]-labeled proteins that enable in situ
      measurements of surface density changes of adsorbed protein molecules on a solid
      support resulting from the interaction with its specific antibody.

PMID- 17196537
TI  - Neural predictors of purchases.
AB  - Microeconomic theory maintains that purchases are driven by a combination of
      consumer preference and price. Using event-related fMRI, we investigated how
      people weigh these factors to make purchasing decisions. Consistent with
      neuroimaging evidence suggesting that distinct circuits anticipate gain and loss,
      product preference activated the nucleus accumbens (NAcc), while excessive prices
      activated the insula and deactivated the mesial prefrontal cortex (MPFC) prior to
      the purchase decision. Activity from each of these regions independently
      predicted immediately subsequent purchases above and beyond self-report
      variables. These findings suggest that activation of distinct neural circuits
      related to anticipatory affect precedes and supports consumers' purchasing
      decisions.

PMID- 17196539
TI  - Synergisms between yellow mustard mucilage and galactomannans and applications in
      food products--a mini review.
AB  - Yellow or white mustard (Sinapis alba L.) is unique in the mustard family by
      containing large amounts of mucilaginous material in the seed coat. This material
      was shown to exhibit similar rheological properties to xanthan gum such as shear
      thinning flow behavior and weak gel structure. This review will discuss the
      synergistic interactions between yellow mustard mucilage (YMM) and
      galactomannans, particularly locust bean gum (LBG), and its potential food
      applications. In addition, synergistic interactions between YMM, with or without
      LBG, on starch paste viscosity and syneresis will also be reviewed. The
      thickening, texturizing and stabilizing properties of YMM, and its ability to
      form gels at very low concentration in the presence of LBG, could lead to many
      food and industrial applications.

PMID- 17196540
TI  - Composite interfacial layers containing micro-size and nano-size particles.
AB  - Surface layers of micro- and nanoparticles at fluid/liquid interfaces in absence
      and presence of surfactants are of large importance in the process of re
      discovering Pickering systems, i.e. emulsions and foams stabilized by particles.
      The surface pressure/area isotherms of such layers can provide information about
      the properties of the used particles (dimensions, interfacial contact angles),
      the structure of interfacial layers, the interactions between the particles as
      well as about relaxation processes within the layers. For a correct description
      of Pi-A isotherms of composite surface layers containing particles the
      significant difference in size of these particles to that of solvent and
      surfactant molecules should be taken into account. Corresponding equations can be
      derived on the basis of the two-dimensional solution theory. The gained equations
      provide satisfactory agreement with experimental data and predict realistic
      values for the area of particles at the interface. Also equations of state and of
      the dilational elasticity for composite surface layers containing particles can
      be obtained in the framework of the presented methodology.

PMID- 17196541
TI  - Mechanism of oil uptake during deep-fat frying and the surfactant effect-theory
      and myth.
AB  - Three mechanisms have been previously proposed to explain the complex process of
      oil uptake during deep-fat frying. The mechanisms reviewed are water replacement,
      cooling-phase effect and surface-active agents. The former mechanism describes
      mainly oil uptake of relatively large voids in the fried food created due to
      water evaporation. The second mechanism furnishes an explanation for the
      significant amount of oil absorbed when the food is removed from the fryer. At
      this point, product surface characteristics and oil viscosity play paramount
      roles. Surface-active agents' formation provides only a limited explanation for
      the increased oil uptake during prolonged frying. Reviewed literature, theory and
      new data show contradicting values and do not support the myth that during
      extended frying time the surfactants generated reduce the contact angle and/or
      the interfacial tension, and consequently, influence oil uptake significantly.
      Higher oil uptake after extended frying time is probably related to higher oil
      viscosity caused by polymerization reactions and oil adherence to the product
      surface. Further research is needed for establishing the interrelationships
      between surface-active agents' formation and their effect on fried product oil
      uptake and quality to resolve this myth.

PMID- 17196542
TI  - One-step procedure for staining of proteins with ruthenium II tris
      (bathophenanthroline disulfonate).

PMID- 17196543
TI  - Modification of the Stewart biphasic colorimetric assay for stable and accurate
      quantitative determination of Pluronic and Tetronic block copolymers for
      application in biological systems.
AB  - Block copolymers are increasingly being applied in areas such as transfection,
      membrane sealing, site-specific targeting, and bionanoengineering yet there is a
      relative paucity of assays available for simple, stable and reproducible
      colorimetric determination of copolymer concentration in solution. We have
      focused on improving the accuracy and reproducibility of a modified version of
      the Stewart biphasic colorimetric assay for quantitative determination of
      Pluronic (poloxamer) and Tetronic (poloxamine) macromolecules. The optimized
      assay achieved linear response ranges in chloroform for commonly used copolymers
      such as poloxamine 904 (20-300 microg/ml), poloxamine 908 (10-400 microg/ml),
      poloxamer 402 (20-400 microg/ml), and poloxamer 407 (10-400 microg/ml). Variation
      in the type of chlorinated solvent used significantly increased assay
      sensitivity, presumably through macromolecular reorientation, affording increased
      access for copolymer-ferrothiocyanate complexation. This was found to be
      optimally favored by the planar geometry of the solvent cis 1,2-dichloroethylene.
      For application to biological systems copolymer-protein interactions were for the
      first time determined and were found to be dependent on the fraction of
      hydrophobic constituents of the block copolymers and protein type. For instance
      serum albumin was found to interact with copolymers of low hydrophilic-lipophilic
      balance values and poly(propylene oxide) contaminants, whereas this interaction
      was not significant with the relatively hydrophilic IgG. In such systems the
      colorimetric assay directly determines the fraction of unbound (free) copolymer
      in the presence of proteins.

PMID- 17196544
TI  - Dry reagent dipstick test combined with 23S rRNA PCR for molecular diagnosis of
      bacterial infection in arthroplasty.
AB  - Periprosthetic joint infections present a challenging problem in orthopaedics.
      Conventional methods for detection of arthroplasty infections rely on bacterial
      culture of synovial fluid aspirates. During recent years, however, molecular
      tests that are based on DNA amplification by the polymerase chain reaction (PCR),
      followed by electrophoretic analysis of the products, have been introduced. We
      report a simple and inexpensive assay that allows visual detection and
      confirmation of the PCR-amplified sequences by hybridization within minutes. The
      assay is performed in a dry reagent dipstick format (strip) and does not require
      special instrumentation. Universal primers are used for PCR of the 23S ribosomal
      RNA (rRNA) gene. The biotinylated amplification product is hybridized with dA
      tailed probes that are specific for six pathogens commonly involved in
      periprosthetic joint infections. The mixture is applied to the strip, which is
      then immersed in the appropriate buffer. The buffer migrates along the strip by
      capillary action and rehydrates gold nanoparticles with oligo(dT) strands
      attached to their surface. The nanoparticles bind to the target DNA through
      hybridization, and the hybrids are captured by immobilized streptavidin at the
      test zone of the strip, producing a characteristic red line. Unbound
      nanoparticles are captured by immobilized oligo(dT) strands at the control zone
      of the strip, generating a second line. The dipstick test was applied to the
      detection of Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis,
      Streptococcus pneumoniae, Enterococcus faesium, and Haemophilus influenza. Twelve
      samples of synovial fluids from patients were analyzed for the detection and
      identification of the infection caused by the six pathogens. The results were
      compared with bacterial cultures.

PMID- 17196545
TI  - Challenges of developing the complex socio-technical system: realising the
      present, acknowledging the past, and envisaging the future of vessel traffic
      services.
AB  - This paper raises the question of how to guide the development of an emerging
      complex socio-technical system. The empirical basis for the discussion is a study
      of Vessel Traffic Services (VTS). We analysed the current state and the history
      of the service in Finland in four studies and identified several development
      needs. The results showed that there are differences between the outcome,
      practices and conceptions of the core task across different experts in the VTS
      centres, which can be explained by the current state of the constituents and the
      history of the activity system. Qualitatively different development phases
      characterised either by a top-down standardisation or bottom-up construction
      process were recognised. A combination of these processes was suggested for the
      future development strategy of the VTS. This could allow both continuous
      development within VTS and recognition of the need for a new system. A promising
      way to achieve continuous development is by creating reflective practices
      supported for instance with annual simulator exercises aimed at procedure
      development. We conclude that solving the current problems and promoting the
      development of the complex system call for a dynamic, open vision of the target
      future of the system, in which the pressures from the social, political and
      technological environments are taken into account. The results of ergonomics
      studies can help in self-reflecting, envisaging and developing supportive methods
      for the system but the persons within the system create the will to develop and
      find their way towards the development horizon.

PMID- 17196546
TI  - An approach towards artificial quinone pools by use of photo- and redox-active
      dendritic molecules.
AB  - Molecules with one porphyrin and multiple quinone groups are described. The
      molecules are based on dendritic frameworks, with the quinone groups attached at
      the "internal" positions and the porphyrin attached at the focal point, leading
      to a characteristic layer architecture. When irradiated with visible light in the
      presence of 4-tert-butylthiophenol, the quinones were converted to quinols. Such
      a behavior mimics the function of quinone pools in photosynthesis.

PMID- 17196547
TI  - A randomised controlled trial of group debriefing.
AB  - There has never been published a randomised controlled trial of group debriefing.
      In this study we employed an analogue study with students to conduct the first
      such trial. Sixty-four participants were shown a stressful video of paramedics
      attending to injured and dead victims of a road traffic accident. Half the
      participants were subsequently debriefed and half were provided with tea and
      biscuits and allowed to talk amongst themselves. A 1 month follow-up was
      administered. It was found that, while the video was rated as distressing, there
      were no significant differences between the debriefed and non-debriefed groups on
      measures of affective distress and trauma symptoms. Those who were debriefed
      later recalled having wanted to talk more to someone about the video than those
      who were not debriefed. It is suggested that cognitive dissonance may explain
      this result.

PMID- 17196548
TI  - Alternative splicing generates a novel non-secretable cytosolic isoform of NELL2.
AB  - NELL2 is as a neuron-specific secreted glycoprotein. The present study provides
      evidence of an alternatively spliced variant of the rat NELL2 gene that yields
      cytosolic NELL2 (cNELL2). cNELL2 was initially detected in the thymus and
      subsequently found to be ubiquitously expressed in many other tissues. The
      absence of the sequences corresponding to the third exon, which contains the
      terminal portion of the signal peptide, accounts for the uniform distribution of
      cNELL2 throughout the cytoplasm. This is in contrast to NELL2, which is
      preferentially located at distinct subcellular structures involved in the
      secretary process, such as endoplasmic reticulum and Golgi apparatus. Western
      blot analysis showed that cNELL2 was not present in the medium but only in
      lysates, while NELL2 was detected as a glycosylated larger form in both lysates
      and media. Immunoprecipitation analysis revealed that cNELL2 interacts with
      PKCbeta1. These results suggest that cNELL2 is involved in PKCbeta1-mediated
      intracellular signaling.

PMID- 17196549
TI  - Beta-catenin up-regulates Nanog expression through interaction with Oct-3/4 in
      embryonic stem cells.
AB  - It is well known that mouse embryonic stem (ES) cells can be maintained by the
      presence of leukemia inhibitory factor (LIF). Recent studies have revealed that
      Wnt also exhibits activity similar to LIF. The molecular mechanism behind the
      maintenance of ES cells by these factors, however, is not fully understood. In
      this study, we found that LIF enhances level of nuclear beta-catenin, a component
      of the Wnt signaling pathway. Expression of an activated mutant of beta-catenin
      led to the long-term proliferation of ES cells, even in the absence of LIF.
      Furthermore, it was found that beta-catenin up-regulates Nanog in an Oct-3/4
      dependent manner and that beta-catenin physically associates with Oct-3/4. These
      results suggest that up-regulating Nanog through interaction with Oct-3/4
      involves beta-catenin in the LIF- and Wnt-mediated maintenance of ES cell self
      renewal.

PMID- 17196550
TI  - Proteomic analysis of spinal cord of presymptomatic amyotrophic lateral sclerosis
      G93A SOD1 mouse.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, whose
      primary mechanisms or causes are still not defined and for which no effective
      treatment is available. We have recently reported that before disease onset the
      level of tyrosine nitrated proteins is increased in the G93A SOD1 transgenic
      mouse model of ALS. In the present investigation, we carried out a proteomic
      analysis of spinal cord extracts from G93A SOD1 mice at the presymptomatic stage
      of the disease to further unravel primary events in the pathogenesis and
      tentatively screen for potential pharmacological targets. Using a robust two
      dimensional gel electrophoresis-based proteomic approach, we detected a number of
      proteins differentially represented in presymptomatic mice in comparison with
      controls. Alterations of these proteins correlate with mitochondrial dysfunction,
      aggregation, and stress response. Moreover, we found a variation in the isoform
      pattern of cyclophilin A, a molecular chaperone that protects cells from the
      oxidative stress.

PMID- 17196551
TI  - Aquaporin 4 regulates the effects of ovarian hormones on monoamine
      neurotransmission.
AB  - Aquaporin 4 (AQP4) is the predominant water channels in the brain of mammals. Our
      previous study has reported that AQP4 knockout induced sex-specific alterations
      in neurotransmission, indicating that AQP4 might regulate the interaction between
      sex hormones and neurotransmission. In the present study, we found that AQP4
      knockout decreased the concentrations of estrogen and progestogen. Further study
      showed that exogenous estrogen decreased DA and 5-HT in cortex, reduced DA and 5
      HT in striatum, but increased 5-HT in hippocampus in AQP4+/+ male mice. However,
      in AQP4-/- male mice, exogenous estrogen almost did not alter the levels of
      neurotransmitters except for decreasing DA in cortex. In female mice, ovariectomy
      decreased DA in the striatum of AQP4+/+ mice, but did not alter the levels of DA
      in AQP4-/- mice. These findings reveal for the first time that AQP4 regulates not
      only water and ion homeostasis but also the functions of ovarian hormone and
      neurotransmitter.

PMID- 17196552
TI  - Melanotransferrin induces human melanoma SK-Mel-28 cell invasion in vivo.
AB  - The expression of melanotransferrin (MTf), a membrane-bound glycoprotein highly
      expressed in melanomas, is correlated with tumor vascularization and progression,
      suggesting a proinvasive function associated with MTf in malignant tumors. To
      test this hypothesis, we silenced MTf in human melanoma SK-MEL-28 cells using
      small interfering RNA (siRNA) and examined the plasmin activity and invasiveness
      of MTf-silenced melanoma. In vitro, the siRNA-mediated MTf knockdown inhibited by
      58% the cell surface activation of plasminogen into plasmin. In addition,
      decreased expression of MTf in melanoma cells reduced cell migration. In vivo, we
      used a nude mice invasion model in which tissue factor (TF) induces vascular
      [125I]-fibrin deposition following injection. Using this metastasis model, the
      invasive potential of MTf-silenced cells into the lungs was reduced by fivefold.
      Altogether, these findings strongly suggest that MTf overexpression in melanoma
      cells contributes to tumor progression by stimulating plasmin generation as well
      as cell migration and invasion.

PMID- 17196553
TI  - Histamine augments beta2-adrenoceptor-induced cyclic AMP accumulation in human
      prostate cancer cells DU-145 independently of known histamine receptors.
AB  - Androgen-independent prostate cancer cells DU-145 express a number of G protein
      coupled receptors, including histamine H1 receptors. There is evidence for the
      presence of beta-adrenoceptors in the human prostate, and in this work we set out
      to characterise the expression of beta-adrenoceptors by DU-145 cells, their
      linking to cyclic AMP (cAMP) formation and the possible modulation by histamine
      H1 receptors of beta-adrenoceptor function. Saturation [3H]-dihydroalprenolol
      binding indicated that DU-145 cells express moderate levels of beta-adrenoceptors
      (22.7+/-2.5 fmol/mg protein), which belong to the beta2-subtype as assessed by
      inhibition by the antagonists ICI-118,551 and CGP-20712A. Inhibition of [3H]
      dihydroalprenolol binding by agonists (noradrenaline, adrenaline and
      isoproterenol) showed the presence of both high-(53-59%) and low-affinity binding
      sites. beta-Adrenoceptor stimulation with isoproterenol resulted in robust [3H]
      cAMP accumulation (10-30-fold of basal, EC50 142 nM; pEC50 6.85+/-0.05). While
      not having effect of its own on basal [3H]-cAMP accumulation, histamine
      significantly augmented the beta2-adrenoceptor-induced response (overall effect
      152+/-6% of isoproterenol alone) with EC50 1.35 microM (pEC50 5.87+/-0.06). This
      effect was independent of extracellular Ca2+, insensitive to antagonists/agonists
      at H1, H2 or H3/H4 receptors and mimicked by drugs containing an imidazole ring
      in their chemical structure and by imidazole itself. Taken together, our results
      show that in DU-145 cells histamine augments beta2-adrenoceptor-induced cAMP
      independently of the activation of known histamine receptors. The effect may
      involve other mechanisms such as allosteric modulation of beta2-adrenoceptors by
      the imidazole moiety of histamine.

PMID- 17196554
TI  - An electrophysiological comparison of recollection for emotional words using an
      exclusion recognition paradigm.
AB  - The positive-going shift of event-related potential (ERP) components that occur
      when recognizing emotional words has been thought to be due to valence effects on
      either recollection or familiarity. This study investigated the independent
      contributions of recollection and familiarity on recognition of emotional words
      in order to examine which is thus responsible for the greater magnitude of ERP
      components seen in response to recognition of emotional, as opposed to neutral
      words. ERPs were measured while participants completed an exclusion recognition
      task. In the test phase, participants were required to respond "old" only to
      target items, which were included in one of two lists that were presented in the
      study phase. They were also asked to respond "new" to distracters and non-target
      items that were in the other previously presented list. "Old" responses to
      targets and non-targets were contrasted with an ERP analysis. Results suggested
      that the late positivity reflected recollection. The magnitude of this
      positivity, elicited around the left parietal area, was greater for negative
      stimuli compared to neutral and positive stimuli. The findings of the present
      study suggested that enhanced recollection of negative words may contribute to
      increased magnitudes of components such as the LPC. The emotional valence of
      words may have separate behavioral and electrophysiological effects on
      recollection and familiarity.

PMID- 17196557
TI  - Cholinergic modulation of sensory interference in rat primary somatosensory
      cortical neurons.
AB  - Sensory interaction was studied using extracellular recordings from 275 neurons
      in the primary somatosensory (SI) cortex of pentobarbital-anesthetized rats.
      Tactile stimulation was applied to the receptive field using a 1 mm diameter
      probe that indented the skin for 20 ms, at 0.5 Hz, (test stimulus). Tactile test
      responses of SI neurons decreased during simultaneous application of a gentle
      tickling (distracter stimuli) continuously for 60 s on a separate receptive field
      located in the same or the contralateral hindlimb (ipsi- or contralateral
      distraction). This decrease in neural response produced by distracter stimuli was
      interpreted as "sensory interference". Sensory interference was observed in 66%
      and 61% of recorded SI neurons when ipsi- or contralateral distracters were
      applied, respectively and was blocked by a novel stimulus obtained by increasing
      the stimulation frequency of the test tactile stimuli from 0.5 to 2 Hz. The
      number of neurons showing sensory interference in response to a contralateral
      distracter was not modified after corpus callosum transection, suggesting that
      interhemispheric connections are not crucial for sensory interference. In
      contrast, the number of neurons showing sensory interference decreased in animals
      with 192 IgG-saporin basal forebrain lesions that decreased the number of
      cortical cholinergic fibers. This finding indicates that cholinergic afferents
      from the basal forebrain are fundamental to sensory interference and suggests
      that the associative cortices - basal forebrain - sensory cortices network may be
      implicated in sensory interference.

PMID- 17196556
TI  - Reduction in CHT1-mediated choline uptake in primary neurons from presenilin-1
      M146V mutant knock-in mice.
AB  - The memory loss in Alzheimer's disease (AD) has been linked to cholinergic
      hypoactivity. Mutations in presenilin-1 (PS-1) may regulate cholinergic
      signaling, although their precise roles in cholinergic neurotransmission in AD
      are unsettled. Neuronal uptake of choline via the high affinity choline
      transporter (CHT1) is essential for cholinergic neurotransmission. CHT1 is a Na+
      dependent, hemicholinium-3 (HC-3)-sensitive choline transporter. Although
      cholinergic neurons in the nucleus basalis of Meynert are a major source of
      cholinergic projections for the cerebral cortex, it is unclear whether cortical
      neurons exhibit intrinsic CHT1 activity that is altered in AD. We now report that
      primary cortical neurons express intrinsic and biologically active CHT1, and
      that, in these neurons, CHT1-mediated choline uptake activity is significantly
      reduced in PS-1 M146V mutant knock-in mice. Further kinetic studies using HC-3
      binding and cell surface biotinylation assays showed that the PS-1 mutation
      inhibits CHT1 mediated choline uptake by reducing the ligand binding affinity of
      CHT1 without significantly altering levels of CHT1 expression in the plasma
      membrane. Since human neocortex has recently been shown to possess intrinsic
      cholinergic innervation, our results indicate that alterations in CHT1-mediated
      high affinity choline uptake in cortical neurons may contribute to Alzheimer's
      dementia.

PMID- 17196555
TI  - Dopaminergic development of prenatal ventral mesencephalon and striatum in
      organotypic co-cultures.
AB  - Using organotypic co-cultures of rat embryonic day 14 (E14) ventral mesencephalon
      (VM) and E21 striatum, we have described the developmental changes in (i)
      dopamine (DA) neurochemistry; (ii) numbers of DA neurons; and (iii) protein
      expression of tyrosine hydroxylase (TH), DA transporter (DAT), and glutamic acid
      decarboxylase (GAD 65/67), over 17 days in vitro (DIV). Co-cultures demonstrated
      changes in DA development similar to those observed in vivo. The numbers of VM DA
      neurons remained relatively constant, while levels of VM DA progressively
      increased through 10 DIV. After 3 DIV, the levels of striatal DA increased
      substantially, through 10 DIV. Tissue levels of DA metabolites homovanillic acid
      (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) reflected changes in tissue DA
      concentrations, indicating that release and metabolism of DA are similar to these
      characteristics observed in vivo. Western blot analysis of TH protein expression
      revealed large increases in VM TH after only 3 DIV, followed by a decline in
      levels through 17 DIV; levels of striatal TH, in contrast, increased through this
      period. Additionally, DAT and GAD 65/67 expression increased, in both the VM and
      striatum, over 17 DIV. By 17 DIV, many measures of DA function had decreased from
      those assessed at 10 DIV, thus providing an approximate limit to the effective
      duration of use of this co-culture model. Our results provide a much-needed
      description of the neurochemical changes that occur during the maturation of VM
      and striatum in organotypic co-cultures. Additionally, these results provide a
      foundation for future studies to assess toxic challenges of the developing
      nigrostriatal DA system, in vitro.

PMID- 17196559
TI  - Efferent connections of the parabigeminal nucleus to the amygdala and the
      superior colliculus in the rat: a double-labeling fluorescent retrograde tracing
      study.
AB  - The parabigeminal nucleus (Pbg) is a subcortical visual center that besides
      reciprocal connections with the superior colliculus (SC), also projects to the
      amygdala (Am). The Pbg-Am connection is part of a multineuronal pathway that
      conveys extrageniculostriate inputs of the retina to the Am, and it rapidly
      responds to the sources of threat before conscious detection. The present study
      demonstrates that Pbg projects bilaterally to Am and SC. The ipsilateral
      projections arise from separate cell populations, whilst the contralaterally
      projecting Pbg neurons emit branching axons that simultaneously innervate Am and
      SC.

PMID- 17196561
TI  - Sound-induced changes of infraslow brain potential fluctuations in the medial
      geniculate nucleus and primary auditory cortex in anaesthetized rats.
AB  - Recent publications indicate the presence of infraslow activity (<0.5 Hz) in
      subcortical and cortical sites of the auditory system of the brain. It has been
      reported that this activity might be sensitive to acoustic stimuli. Yet the
      dynamics of infraslow brain potential (ISBP) fluctuations in these structures and
      their potential sensitivity to auditory stimuli are unknown. The present study
      was performed in order to test the hypothesis that extracellular ISBP activity in
      the medial geniculate nucleus (MGN) and the primary auditory cortex (A1) responds
      concurrently to acoustic stimuli. The experimental subjects were 5 adult rats
      with chronic stereotaxic electrodes implanted in MGN and A1. The animals were
      anesthetized and recordings were made in both sites during both silence and
      rhythmical acoustic stimulation. Our results support the hypothesis that these
      fluctuations are sensitive to acoustic stimuli. There were similar changes in
      ISBP activity in the MGN and A1 in response to rhythmic acoustic stimulation.
      Specifically, there were significant increases in the frequency range of seconds.
      Based on these findings, we suggest that sound-correlated changes in infraslow
      activity in the range of seconds in the MGN and A1 reflect specific mechanisms of
      neural processing of acoustic information in the auditory system of the brain.

PMID- 17196558
TI  - Magnetic resonance lactate and lipid signals in rat brain after middle cerebral
      artery occlusion model.
AB  - Proton magnetic resonance spectroscopy (1-H MRS) has revealed changes of
      metabolites in acute cerebral infarction. Although the drastic changes of lactate
      and N-acetyl-aspartate have been reported to be useful indicators of the ischemic
      damage in both humans and experimental animals, lipid signals are also detected
      by the short echo time sequence 1-5 days after ischemia. The objective of this
      study was to find a novel technique to isolate lactate signals from lipid signals
      in the ischemic brain. First, MRS was used to study the lipid and lactate
      components of a spherical phantom in vitro, and parameters were established to
      separate these components in vitro. Then, MR measurements were obtained from the
      brains of middle cerebral artery occlusion rats. All MR measurements were
      performed using a 7-T (300 MHz), 18.3-cm-bore superconducting magnet (Oxford
      Magnet Technologies) interfaced to a Unity INOVA Imaging System (Varian
      Technologies). T2-weighted images were obtained from a 1.0-mm-thick coronal
      section using a 3-cm field of view. It is well known that lipid has a shorter and
      lactate a longer T2 relaxation time. These distinct magnetic characteristics
      allowed us to separate the lactate signal from the lipid signal. Thus, adjustment
      of the echo time is essential to analyze the metabolites in acute cerebral
      infarction, which may be useful in both the clinic and laboratory.

PMID- 17196562
TI  - Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1
      gangliosidosis: possible use for assessment of a therapeutic regimen.
AB  - The present study investigated cerebrospinal fluid (CSF) biomarkers for
      estimating degeneration of the central nervous system (CNS) in experimental dogs
      with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term
      glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified
      here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and
      multiple systemic organs, is due to an autosomal recessively inherited deficiency
      of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may
      include neuronal apoptosis and abnormal axoplasmic transport and inflammatory
      response, which are perhaps consequent to massive neuronal storage of GM1
      ganglioside. In the present study, we assessed some possible CSF biomarkers, such
      as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase
      (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic
      studies demonstrated that GM1 ganglioside concentration, activities of AST and
      LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs
      with GM1 gangliosidosis than those in control dogs, and their changes were well
      related with the months of age and clinical course. In conclusion, GM1
      ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing
      CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of
      novel therapies proposed for this disease. In addition, we preliminarily treated
      an affected dog with long-term oral administration of prednisolone and evaluated
      the efficacy of this therapeutic trial using CSF biomarkers determined in the
      present study. However, this treatment did not change either the clinical course
      or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy
      would not be effective for treating GM1 gangliosidosis.

PMID- 17196560
TI  - NMDA receptor-mediated excitotoxicity contributes to the cerebral hypoxic injury
      of a rat model of posthypoxic myoclonus.
AB  - Cardiac arrest-induced cerebral hypoxic injury could induce posthypoxic movement
      disorders. Here we investigated the effects of memantine, an NMDA receptor
      channel blocker, on the neurodegeneration occurred in an established rat model of
      posthypoxic myoclonus. We found that administration of memantine for 7 days
      significantly reduced cerebral hypoxia-induced neurodegeneration in the CA1 of
      the hippocampus, the reticular thalamic nucleus (RTN) and the primary fissure of
      the cerebellum of the posthypoxic animals. The results suggest that the
      neurodegeneration observed in specific areas of the brain of the posthypoxic rats
      is contributed by NMDA receptor-mediated excitotoxicity.

PMID- 17196563
TI  - Prenatal opiate exposure attenuates LPS-induced fever in adult rats: role of
      interleukin-1beta.
AB  - Much is known about the immunomodulatory effects of opiate exposure and
      withdrawal in adult rats. However, little research has delved into understanding
      the immunological consequences of prenatal opiate exposure and postnatal
      withdrawal. The purpose of the current study was to measure changes in responding
      to immune stimulation in adult rats following prenatal opiate exposure. Further,
      we sought to characterize the role of interleukin (IL)-1beta in these changes.
      Following prenatal exposure to the long-acting opiate l-alpha-acetylmethadol
      (LAAM), adult male and female rats were assessed for their fever response to
      lipopolysaccharide (LPS). Blood and tissue samples were collected to measure
      circulating IL-1beta and IL-1beta protein in the hypothalamus and spleen.
      Prenatal LAAM exposure resulted in a blunted fever response to LPS injection
      without any changes in basal body temperature or in response to saline injection.
      Circulating IL-1beta was not affected by prenatal LAAM exposure, nor was IL-1beta
      protein in the spleen. Interestingly, mature IL-1beta protein was elevated in the
      hypothalamus of prenatally LAAM-treated rats. These results indicate that
      prenatal opiate exposure blunts the fever response of adult offspring. Direct
      action of IL-1beta is likely not the cause of the dysfunction reported here.
      However, alterations in signaling mechanisms downstream from IL-1beta may play a
      role in the altered fever response in adult rats treated prenatally with opiates.

PMID- 17196564
TI  - The novel adenosine A2a antagonist ST1535 potentiates the effects of a threshold
      dose of l-dopa in unilaterally 6-OHDA-lesioned rats.
AB  - Adenosine A2a antagonists can modulate dopamine-mediated motor behaviours,
      however, their ability to induce rotational behaviour in 6-hydroxydopamine (6
      OHDA)-lesioned rats and to potentiate the effects of l-dopa differs. We now
      report on the effects of the novel A2a antagonist ST1535 on rotational responses
      in this model. When administered alone, ST1535 (2.5-40 mg/kg po) enhanced
      exploratory behaviour and produced a dose-related increase in ipsilateral
      rotation in rats with a unilateral 6-OHDA lesion of the nigro-striatal pathway.
      Administration of ST1535 (40 mg/kg po) in combination with a high dose of l-dopa
      (12 mg/kg ip) caused marked contraversive rotation but did not alter the
      rotational response produced by l-dopa alone. In contrast, when administered in
      combination with l-dopa (7 mg/kg ip) that alone produced a submaximal circling
      response, ST1535 enhanced the intensity and duration of rotation. These results
      suggest that ST1535 is able to alter dopamine-mediated behaviour when given alone
      and to potentiate the effects of submaximal doses of l-dopa. ST1535 may be useful
      in the treatment of Parkinson's disease and effective in reducing the use of l
      dopa.

PMID- 17196565
TI  - The endothelial glycocalyx affords compatibility of Starling's principle and high
      cardiac interstitial albumin levels.
AB  - OBJECTIVE: To test the role of an oncotic pressure gradient across the
      endothelial glycocalyx with respect to extravasation of fluid and colloids and
      development of tissue edema in a whole organ setting. METHODS: We measured
      filtration in the intact coronary system of isolated guinea pig hearts, comparing
      colloid-free perfusion and perfusion with 1.67% albumin or 2% hydroxyethylstarch
      (oncotic pressures 5.30 vs. 11.10 mm Hg, respectively). Heparinase was used to
      alter the endothelial glycocalyx. RESULTS: Extremely high net organ hydraulic
      conductivity was obtained with colloid-free perfusion (9.14 microl/min/g tissue).
      Supplementing perfusate with albumin caused a significant decrease, also vs.
      hydroxyethylstarch (1.04 vs. 2.67 microl/min/g, p < 0.05). Albumin also lowered
      edema formation vs. the other perfusion modes (p < 0.05). Stripping the
      glycocalyx of heparan sulfate reduced the effect of colloids, especially that of
      albumin. The steady-state concentrations of hydroxyethylstarch and albumin in the
      mixed interstitial fluid leaving the intact coronary bed averaged about 95% of
      the intravascular level. Electron and light microscopy indicated that colloid
      extravasated mainly in the venular sections. CONCLUSION: We propose a low
      filtration model for the coronary system with different barrier properties in
      arteriolar/capillary and venular sections. Arteriolar/capillary: very little
      fluid and colloid extravasation due to the endothelial surface layer formed by
      the glycocalyx and albumin plus the endothelial strand barrier; venular: little
      net extravsation of fluid and colloids despite large pores, because of low
      hydrostatic and oncotic pressure differences between intra- and extravascular
      spaces. The latter sites provide physiological access of large solutes (colloids)
      to the tissue.

PMID- 17196566
TI  - Viral or non-viral angiogenesis gene transfer-New answers to old questions.

PMID- 17196567
TI  - Triggering of cardiac preconditioning through Na+/K+-ATPase.

PMID- 17196569
TI  - Proarrhythmic electrical remodelling is associated with increased beat-to-beat
      variability of repolarisation.
AB  - OBJECTIVE: Acquired long-QT syndrome in combination with increased beat-to-beat
      variability of repolarisation duration (BVR) is associated with lethal torsades
      de pointes arrhythmias (TdP) in dogs with remodelled heart after atrioventricular
      block (AVB). We evaluated the relative contributions of bradycardia and
      ventricular remodelling to proarrhythmic BVR with and without pharmacological
      I(Kr) block in order to identify the individual at risk. METHODS: Three groups of
      dogs were used: sinus rhythm dogs (n = 12), dogs with acute AVB (n = 8), and dogs
      with >3 weeks chronic AVB (n = 27). Under anaesthesia, ECG and monophasic action
      potential duration (MAPD) were measured. Local BVR was quantified as short-term
      variability from 30 consecutive left ventricular MAPD (STV = summation absolute
      value(D(n(i)-D(n+1))/[30 x square root of 2])). All dogs received dofetilide iv.
      RESULTS: The slower ventricular rate acutely after AVB affected neither QTc nor
      STV (288+/-18 to 293+/-38 ms and 0.7+/-0.1 to 0.7+/-0.1 ms, respectively; P = NS
      for both), whereas ventricular remodelling increased both (to 376+/-46 and 2.3+/
      0.6 ms, respectively; P < 0.05 for both). Neither dogs in sinus rhythm nor acute
      AVB showed any TdP, whereas dofetilide induced TdP in 74% of the chronic-AVB
      dogs. Dofetilide increased the QTc interval in all groups (19-24%; P < 0.05 for
      all groups), whereas STV was elevated in chronic-AVB dogs only (to 4.2+/-1.5 ms;
      P < 0.05) and further confined to inducible chronic-AVB dogs (5.0+/-0.8 versus
      1.9+/-0.4 ms for resistant dogs; P < 0.05). Variability of the idioventricular
      rate was increased directly after AVB and did not influence BVR. CONCLUSIONS:
      Under drug-free circumstances, a persistent high BVR in chronic-AVB dogs is
      remodelling dependent rather than a direct consequence of bradycardia acutely
      after AVB. Variability of this slower rate does not influence BVR. Dofetilide
      causes a transient increase in BVR only in proarrhythmic dogs. Thus, BVR may aid
      the identification of the TdP-susceptible patient.

PMID- 17196568
TI  - The role of poly(ADP-ribose) polymerase (PARP) in the autonomous proliferative
      response of endothelial cells to hypoxia.
AB  - OBJECTIVE: The autonomous proliferative response of endothelial cells to hypoxia
      has been shown to be dependent on activation of NAD(P)H oxidase, on the cytosolic
      Ca2+ load, and, consequently, on nuclear translocation of extracellular signal
      regulated kinase (ERK)1/2 during transient hypoxia. The aim of the present study
      was to investigate whether poly(ADP-ribose) polymerase (PARP) is a downstream
      signal of NAD(P)H oxidase, mediating cytosolic Ca2+ load and hence nuclear
      translocation of ERK1/2 and endothelial cell proliferation. METHODS: Porcine
      aortic endothelial cells were incubated under hypoxic conditions for 40 min.
      Cytosolic [Ca2+] and reactive oxygen species (ROS) formation were measured in
      fura-2- and DCF-loaded cells, respectively. PARP activation was detected by
      immunocytochemistry, and endothelial cell proliferation was determined 24 h after
      60 min of transient hypoxia. RESULTS: Inhibition of NAD(P)H oxidase with
      antisense oligonucleotide against the p22(phox) subunit, MEK/ERK signalling with
      UO 126 (30 microM), or PARP with PJ 34 (10 microM) leads to a marked reduction in
      hypoxia-induced cytosolic Ca2+ load and activation of PARP. Hypoxia-induced
      translocation of ERK1/2 and endothelial cell proliferation were also prevented
      when NAD(P)H oxidase or PARP were inhibited; however, hypoxic ROS formation was
      not affected in the presence of PARP inhibitor. CONCLUSION: PARP represents a
      downstream effector of NADP(H) oxidase and acts as a necessary intermediate step
      for the hypoxic proliferative response of endothelial cells.

PMID- 17196570
TI  - Platelet glycoprotein polymorphisms: risk, in vivo expression and severity of
      atherothrombotic stroke in Chinese.
AB  - BACKGROUND: Polymorphisms in platelet glycoprotein (GP) receptors Ia, Ib and IIIa
      may be heritable risk factors for platelet-dependent thrombosis leading to death.
      The precipitation of stroke by occlusive thrombi has led to the investigation of
      the platelet surface GP receptors, that are involved in critical steps in the
      activation of platelets. Three polymorphisms in the GP Iba gene and one in each
      of GPIIIa, GP Ia were selected based on the evidence of functional effects on
      structure or expression as candidates for risk. We also determined whether these
      polymorphisms were associated with in vivo expression levels of platelet GP
      receptors and the severity of the neurological deficit. METHODS: A Chinese
      hospital-based case-control study was conducted with 119 cases of
      atherothrombotic stroke and 166 age and sex matched controls. Genotyping was
      performed on lymphocyte DNA by standard methods and platelet GP expression levels
      were measured by flow-cytometry. RESULTS: Allele and genotype frequencies of the
      GP receptor polymorphisms differ considerably between ethnic populations. We
      found the D allele of the GP Iba VNTR polymorphism was significantly associated
      with atherothrombotic stroke in our Chinese cohort, however we did not find a
      relationship among these polymorphisms, the expression levels of GP receptors and
      severity of the neurological deficit. CONCLUSIONS: In our Chinese cohort the D
      allele of the GP Iba VNTR polymorphism is associated with atherothrombotic
      stroke. The number of VNTR repeats alters the length of amino acid sequence,
      which might affect the structure and function of this receptor.

PMID- 17196571
TI  - Comparison of whole blood interleukin-8 and plasma interleukin-8 as a predictor
      for sepsis in postoperative patients.
AB  - OBJECTIVE: Interleukin-8 (IL-8, also known as neutrophil-activating peptide 1,
      NAP1 and CXCL8, CXC chemokine ligand 8) is recognized as a potent effector of
      neutrophil functions. IL-8 is a major response factor following NfkB activation
      by cytokines or lipopolysaccharide and several different cell types T
      lymphocytes, monocytes, epithelial and endothelial cells secrete this
      polypeptide. IL-8 is not to be determined at significant concentrations in plasma
      due to its receptor binding but may play a major role in tissues. The prediction
      of sepsis is a major and current field of research in the treatment of surgical
      patients. The aim of this study was to compare the determination of IL-8 in whole
      blood cell lysates (whole blood IL-8) and in plasma for the prediction of sepsis
      in postoperative intensive care. DESIGN: Whole blood IL-8, IL-8 in plasma, and
      CRP were measured in the daily routine monitoring of 84 patients in a surgical
      intensive care unit. Sepsis was defined by the criteria of the Society of
      Critical Care Medicine (SCCM). For comparison the APACHE II score (APACHE=Acute
      Physiology and Chronic Health Evaluation) was calculated. The diagnostic value of
      the three tests was compared by receiver operating characteristic (ROC) curves.
      RESULTS: Whole blood IL-8 showed higher areas under the curve (AUC) than IL-8 in
      plasma and CRP. The ROC curves for the APACHE II scores gave similar results.
      CONCLUSIONS: Sepsis is a complex disease and is induced by systemic infection of
      patients suffering from systemic inflammatory response syndromes (SIRS).
      Therefore, the identification of infection or the host response to infection is
      of crucial importance. The prediction of an individual marker or interleukin or
      its binding to surface proteins is not necessarily indicative for sepsis. In
      cases with unequivocally identified bacterial infections, the current results
      suggest that whole blood IL-8 may have a similar diagnostic accuracy as plasma
      levels. Of note, this technique needs less blood and is not being affected by
      hemolysis.

PMID- 17196572
TI  - Genetic analysis of the dystroglycan gene in bronchopulmonary dysplasia affected
      premature newborns.
AB  - BACKGROUND: Dystroglycan (DG) is an extracellular matrix receptor that serves as
      an adhesion molecule and is essential for the stability of the plasma membrane.
      DG is highly expressed within the epithelial cell layer where it supports
      morphogenesis, adhesion and wound repair. Mechanically ventilated newborns often
      develop bronchopulmonary dysplasia (BPD), characterized by a progressive
      impairment of wound repair capacity in their lung. METHODS: To verify if the
      susceptibility to BPD might be linked to genetic abnormalities in the DG gene
      (DAG1), we searched for possible mutations in 33 premature newborns with
      gestational age<34 weeks with risk of developing BPD. DAG1 genotype was
      determined in 11 premature newborns with BPD as compared to 22 premature infants
      without lung complications. RESULTS: Eight polymorphisms were found, four of them
      being new DAG1 single nucleotide polymorphisms (SNPs). Only one significant
      association was found with BPD positive infants: the N494H homozygous genotype
      (p=0.033). The same polymorphism was found significantly associated with BPD when
      allelic frequencies were considered (p=0.0015). CONCLUSIONS: Our data enrich the
      list of DAG1 SNPs and could be useful to trigger further genetic studies about
      the involvement of DG in human diseases.

PMID- 17196574
TI  - Therapeutic evaluation of GM2 gangliosidoses by ELISA using anti-GM2 ganglioside
      antibodies.
AB  - BACKGROUND: GM2 gangliosidoses, including Tay-Sachs disease, Sandhoff disease and
      the AB variant, comprise deficiencies of beta-hexosaminidase isozymes and GM2
      ganglioside activator protein associated with accumulation of GM2 ganglioside
      (GM2) in lysosomes and neurosomatic clinical manifestations. A simple assay
      system for intracellular quantification of GM2 is required to evaluate the
      therapeutic effects on GM2-gangliosidoses. METHODS: We newly established a cell
      ELISA system involving anti-GM2 monoclonal antibodies for measuring GM2 storage
      in fibroblasts from Tay-Sachs and Sandhoff disease patients. RESULTS: We
      succeeded in detecting the corrective effect of enzyme replacement on elimination
      of GM2 in the cells with this ELISA system. CONCLUSIONS: This simple and
      sensitive system should be useful as additional diagnosis tool as well as
      therapeutic evaluation of GM2 gangliosidoses.

PMID- 17196573
TI  - Mass spectrometry analysis of urine and catheter of a patient with purple urinary
      bag syndrome.
AB  - INTRODUCTION: Purple urinary bag syndrome (PUBS) is considered to be a benign
      condition observed in the urinary catheter and bag in some catheterized patients
      with urinary tract infections. This syndrome is usually reported to occur in
      alkaline urine. CASE REPORT: We report of a catheterized patient with PUBS and
      slightly acidic urine (pH 6-6.5). A novel analysis method was developed using
      high pressure liquid chromatography and mass spectrometry (HPLC/MS) to detect
      compounds that are thought to be associated with PUBS. Urine, urinary sediment,
      and the plastic collection system were assayed and quantitated using these
      methods. The potential toxicity of one of these compounds, indoxyl sulfate, is
      discussed. CONCLUSIONS: The presence of PUBS in a catheterized patient with
      slightly acidic urine is reported. A novel method for the analysis of chemical
      components of PUBS and the first direct confirmation of the presence of indigo in
      the urine sediment and collecting system are described.

PMID- 17196576
TI  - Hair analysis of histamine and several metabolites in C3H/HeNCrj mice by ultra
      performance liquid chromatography with electrospray ionization time-of-flight
      mass spectrometry (UPLC-ESI-TOF-MS): influence of hair cycle and age.
AB  - BACKGROUND: According to a previous study, the concentration of HA in the hair of
      SD rats was similar in each rat and the variation in HA concentration was not so
      great. However, the concentration in human hair was fairly different in each
      person. As possible reasons for the higher variation in human hair, the
      differences in hair cycles and age in each person may be considerable. Based on
      this idea, the studies using C3H/HeNCrj mice who can synchronize their hair cycle
      were performed for resolution of the influence of hair cycle and age. METHODS:
      The effects of hair cycle and age on the concentration of histamine (HA) and
      several metabolites, i.e., 1-methylhistamine (MHA), imidazole-4-acetic acid
      (IAA), and 1-methyl-4-imidazole-acetic acid (MIAA), in C3H/HeNCrj mice hair were
      investigated by ultra-performance liquid chromatography (UPLC) with electrospray
      ionization time-of-flight mass spectrometry (ESI-TOF-MS). HA and the metabolites
      were labeled with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole
      (DBD-F) and 4-(N,N-dimethylaminosulfonyl)-7-piperazino-2,1,3-benzoxadiazole (DBD
      PZ). The resulting derivatives were separated by UPLC and determined with ESI-TOF
      MS. RESULTS: A good linearity was achieved from the calibration curves, obtained
      by plotting the peak area ratios of the analytes relative to the internal
      standard (IS), i.e., histamine-alpha,alpha,beta,beta-d4 (HA-d4) or 4
      imidazolecarboxylic acid (ICA), against the injected amounts of each compound.
      The detection limits of HA, MHA, IAA, and MIAA on mass chromatograms were 0.21,
      1.0, 0.17, and 0.11 pmol, respectively. The concentrations of HA and the
      metabolites in the hair shafts and hair root of C3H/HeNCrj mice were determined
      by this method. The concentration of HA in the hair shaft was relatively higher
      in the telogen phase. In contrast, the HA content in the anagen phase was
      increased only in the hair root of old mice. CONCLUSION: HA appears to possess
      some effect on hair growth, although the exact reason was not obvious. The HA
      metabolites, i.e., MHA, MIAA and IAA, were also determined the same as HA;
      however, the difference in the metabolite concentrations between the hair cycle
      and age was not clear in both hair shaft and hair root. Such studies of the
      effect of hair cycle and age on these concentrations are the first report. This
      analytical technique may be applicable to the determination of various biological
      compounds in hair.

PMID- 17196575
TI  - ACE I/D polymorphism study in a Cuban hypertensive population.
AB  - BACKGROUND: The angiotensin converting enzyme (ACE) is a key protein of the renin
      angiotensin system, whose main function is the conversion of angiotensin I to II.
      ACE is involved in the physiological control of blood pressure and it is a
      candidate gene for essential hypertension in humans. We tested the relevance of
      the ACE insertion/deletion (I/D) polymorphism in our population. METHODS: We
      recruited 243 hypertensive and 407 normotensive subjects in the city of Havana,
      matched according to age, sex and ethnic group. The ACE (I/D) polymorphism was
      determined by the polymerase chain reaction (PCR) technique. The fit of genotype
      frequencies to Hardy-Weinberg proportions was evaluated in all groups analyzed.
      The possible association between the ACE I/D polymorphism and hypertension status
      was tested by chi2 and odds ratio tests. RESULTS: All groups but black female
      cases were in Hardy-Weinberg equilibrium. The frequencies of the D allele in
      hypertensive/normotensive subjects were 0.61/0.59 in white males, 0.58/0.58 in
      white females, 0.47/0.59 in black males and 0.58/0.54 in black females. The
      distribution of ACE genotypes differed significantly between cases and controls
      only in black women according to the additive model (chi2p=0.04) but the adjusted
      OR did not show significant association (OR 1.14 95% CI 0.62 to 2.10).
      CONCLUSION: The ACE I/D polymorphism was not associated with hypertension in our
      multiethnic sample. While the chi2 test for additive model in black women
      suggested a marginal significance, the adjusted OR did not show any significant
      association.

PMID- 17196577
TI  - Effect of HbS in the determination of HbA(2) with the TOSOH HLC-723G7 analyzer
      and the HELENA Beta-Thal Quik column kit.
AB  - OBJECTIVES: The analytical performance of the TOSOH HLC-723G7 hemoglobin HPLC
      analyzer and the effect of the presence of HbS in the determination of HbA(2)
      using HPLC and manual column methods. DESIGN AND METHODS: The performance
      characteristics of the TOSOH HLC-723G7 analyzer in the determination of HbA(2)
      were compared to those of the HELENA Beta-Thal Quik column. The effect of HbS
      presence in the samples was quantified using the HELENA SAS-MX alkaline gel
      electrophoresis kit as the reference method. RESULTS: Within-run and between-run
      CVs for HbA(2) were better for the TOSOH HPLC analyzer than for the HELENA manual
      column method. The presence of HbS in the samples produces a strong positive bias
      in the %HbA(2) values when using both the HPLC and manual column methods,
      compared to the alkaline electrophoresis gel. CONCLUSION: Both the TOSOH HPLC and
      the manual column are reliable methods for %HbA(2) determination when no HbS is
      detectable in the samples. When HbS is present, the gel electrophoresis method
      gives more accurate results.

PMID- 17196578
TI  - A novel assay for the evaluation of the prooxidant-antioxidant balance, before
      and after antioxidant vitamin administration in type II diabetes patients.
AB  - OBJECTIVES: The application of a novel assay for the direct measurement of
      prooxidant-antioxidant balance (PAB) in type II diabetes and the evaluation of
      antioxidant therapy. DESIGN AND METHODS: The assay is based on 3,3',5,5'
      tetramethylbenzidine and its cation, used as a redox indicator participating in
      two simultaneous reactions. PAB was determined in the sera of healthy volunteers
      and type II diabetes patients. The results were compared with clinical and
      biological parameters, protein oxidation markers, as well as the results of
      antioxidant and prooxidant assays. PAB, after administration of vitamins C and E
      for 1 day, 1 month and 2 months was also determined. RESULTS: Increased PAB was
      found in the patients' group and correlated with parameters involved in diabetic
      complications, protein oxidation markers, antioxidant and prooxidant assays. One
      day after vitamin administration, a significant shift of PAB towards antioxidants
      was observed. PAB remained unchanged after 1 month and changed marginally in
      favor of prooxidants in the second month of the therapy. CONCLUSIONS: These
      results indicate that the measurement of PAB may be useful to identify and follow
      up patients who need antioxidant therapy.

PMID- 17196579
TI  - Increased DNA damage and oxidative stress in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Oxidative stress has been described as an important mechanism that
      underlies chronic inflammation in rheumatoid arthritis (RA). The aim of the study
      was to investigate the peripheral DNA damage, total antioxidant status (TAS), and
      total oxidative status (TOS) in patients with RA. DESIGN AND METHODS: The study
      population contained 25 patients with RA and 26 healthy controls. DNA damage was
      assessed by alkaline comet assay in peripheral lymphocyte, plasma levels of total
      antioxidant status (TAS) and total oxidative status (TOS) were determined, and
      OSI was calculated using a novel automated measurement method. Disease activity
      was evaluated by DAS-28 score. RESULTS: In RA patients, DNA damage was
      significantly higher than in controls (20.0+/-9.6 AU, 7.6+/-4.3 AU; p<0.001).
      Plasma TOS and OSI were higher in patients than in healthy controls (9.9+/-2.6
      vs. 7.3+/-1.1, p<0.001; 1.04+/-0.4 vs. 0.7+/-0.1, p<0.001, respectively). Plasma
      TAS level in patients was lower than in healthy controls (0.9+/-0.7 vs. 1.01+/
      0.7, p<0.001). DNA damage was correlated with TOS, OSI, and DAS-28 scores
      (r=0.682, p<0.001; r=0.753, p<0.001; r=0.519, p=0.008, respectively).
      CONCLUSIONS: The findings indicated that lymphocyte DNA damage level increases in
      patients with RA. Elevated DNA damage may be related with increased oxidative
      stress and decreased antioxidant capacity. However, the mechanism of this
      association, and whether it is direct or indirect, remains to be explored.

PMID- 17196580
TI  - Hearing what the body feels: auditory encoding of rhythmic movement.
AB  - Phillips-Silver and Trainor (Phillips-Silver, J., Trainor, L.J., (2005). Feeling
      the beat: movement influences infants' rhythm perception. Science, 308, 1430)
      demonstrated an early cross-modal interaction between body movement and auditory
      encoding of musical rhythm in infants. Here we show that the way adults move
      their bodies to music influences their auditory perception of the rhythm
      structure. We trained adults, while listening to an ambiguous rhythm with no
      accented beats, to bounce by bending their knees to interpret the rhythm either
      as a march or as a waltz. At test, adults identified as similar an auditory
      version of the rhythm pattern with accented strong beats that matched their
      previous bouncing experience in comparison with a version whose accents did not
      match. In subsequent experiments we showed that this effect does not depend on
      visual information, but that movement of the body is critical. Parallel results
      from adults and infants suggest that the movement-sound interaction develops
      early and is fundamental to music processing throughout life.

PMID- 17196581
TI  - Cryopreservation of the mouse ovary inhibits the onset of primordial follicle
      development.
AB  - The cryopreservation of ovarian tissue has been reported to affect the
      development of preantral follicles. However, the effect of cryopreservation of
      ovarian tissue on the development of primordial follicles remains to be
      elucidated. This study was conducted to evaluate the effect of cryopreservation
      on the development of frozen-thawed mouse primordial follicles. One-day-old mouse
      ovaries were cryopreserved by either slow-freezing or a vitrification method. The
      development of primordial follicles was evaluated histologically and also with
      markers for follicle development such as: GDF-9, inhibin-alpha subunit and ZP3 in
      fresh and frozen-thawed ovaries cultured for five days. The proportion of
      apoptotic and necrotic areas was analyzed in fresh and frozen-thawed ovaries at
      one and five days after culture, in order to examine the viability of ovarian
      cells that influence primordial follicle development. The development rate of
      primordial follicles was significantly lower in slow-frozen and vitrified ovaries
      than the fresh controls after five days of in vitro culture (P<0.05). The mRNA
      expression for all developmental markers was slightly decreased in the frozen
      thawed ovaries; this difference was not significant. The proportion of apoptosis
      was significantly increased in the slow-frozen and vitrified ovaries compared to
      the fresh ovaries at one day (P<0.05); however, there was no difference at five
      days after culture. The proportion of the area of necrosis was significantly
      higher in slow-frozen and vitrified ovaries compared to the fresh ovaries at one
      and five days after culture (P<0.05). Our preliminary data suggest that ovarian
      tissue cryopreservation using slow-freezing and vitrification methods inhibits
      development of primordial follicles. This may be caused by the death of ovarian
      cells through apoptosis and necrosis after cryopreservation.

PMID- 17196582
TI  - Brn3a target gene recognition in embryonic sensory neurons.
AB  - Numerous transcription factors have been identified which have profound effects
      on developing neurons. A fundamental problem is to identify genes downstream of
      these factors and order them in developmental pathways. We have previously
      identified 85 genes with changed expression in the trigeminal ganglia of mice
      lacking Brn3a, a transcription factor encoded by the Pou4f1 gene. Here we use
      locus-wide chromatin immunoprecipitation in embryonic trigeminal neurons to show
      that Brn3a is a direct repressor of two of these downstream genes, NeuroD1 and
      NeuroD4, and also directly modulates its own expression. Comparison of Brn3a
      binding to the Pou4f1 locus in vitro and in vivo reveals that not all high
      affinity sites are occupied, and several Brn3a binding sites identified in the
      promoters of genes that are silent in sensory ganglia are also not occupied in
      vivo. Site occupancy by Brn3a can be correlated with evolutionary conservation of
      the genomic regions containing the recognition sites and also with histone
      modifications found in regions of chromatin active in transcription and gene
      regulation, suggesting that Brn3a binding is highly context dependent.

PMID- 17196583
TI  - Fibin, a novel secreted lateral plate mesoderm signal, is essential for pectoral
      fin bud initiation in zebrafish.
AB  - We identified a novel secreted protein, fibin, in zebrafish, mice and humans. We
      inhibited its function in zebrafish embryos by injecting antisense fibin
      morpholino oligonucleotides. A knockdown of fibin function in zebrafish resulted
      in no pectoral fin bud initiation and abolished the expression of tbx5, which is
      involved in the specification of pectoral fin identification. The lack of
      pectoral fins in fibin-knockdown embryos was partially rescued by injection of
      fibin RNA. fibin was expressed in the lateral plate mesoderm of the presumptive
      pectoral fin bud regions. Its expression region was adjacent to that of tbx5.
      fibin expression temporally preceded tbx5 expression in presumptive pectoral fin
      bud regions, and not abolished in tbx5-knockdown presumptive fin bud regions. In
      contrast, fibin expression was abolished in retinoic acid signaling-inhibited or
      wnt2b-knockdown presumptive fin bud regions. These results indicate that fibin is
      a secreted signal essential for pectoral fin bud initiation in that it
      potentially acts downstream of retinoic acid and wnt signaling and is essential
      for tbx5 expression. The present findings have revealed a novel secreted lateral
      plate mesoderm signal essential for fin initiation in the lateral plate mesoderm.

PMID- 17196584
TI  - Agricultural exposures and gastric cancer risk in Hispanic farm workers in
      California.
AB  - Previous studies have indicated that farm workers may be at increased risk of
      gastric cancer. Meta-analyses, ecological, case-control, and cohort studies
      suggest that some aspects of the agricultural environment may be implicated in
      the elevated risk. Hispanic farm workers in California are exposed to a multitude
      of potentially toxic substances in the work site, including excessive sunlight,
      fertilizers, diesel fumes, and pesticides. A previous analysis of a cohort of
      California farm workers who had been members of a farm labor union, the United
      Farm Workers of America (UFW) found a proportionate cancer incidence ratio for
      stomach cancer of 1.69 when using the California Hispanic population as the
      standard. The aim of the current study was to further evaluate associations
      between gastric cancer and the types of crops and commodities UFW members
      cultivate and the associated pesticide use as recorded by the California
      Department of Pesticide Regulation (DPR). We conducted a nested case-control
      study of gastric cancer embedded in the UFW cohort and identified 100 cases of
      newly diagnosed gastric cancer between 1988 and 2003. We identified 210 control
      participants matched on age, gender, ethnicity, and who were known to be alive
      and resident in California up to the date of the cases' diagnosis. Both
      stratified analyses and unconditional logistic regression were used to calculate
      adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Work in the
      citrus industry was associated with increased gastric cancer (OR=2.88; 95%
      CI=1.02-8.12) although no other specific crops or commodities were associated
      with this disease. Working in areas with high use of the phenoxyacetic acid
      herbicide 2,4-D was associated with gastric cancer (OR=1.85; 95% CI=1.05-3.25);
      use of the organochlorine insecticide chlordane was also associated with the
      disease (OR=2.96; 95% CI=1.48-5.94). Gastric cancer was associated with use of
      the acaricide propargite and the herbicide triflurin (OR=2.86; 95% CI=1.56-5.23
      and 1.69, 95% CI=0.99-2.89, respectively). Gastric cancer in California Hispanic
      farm workers is associated with work in the citrus fruit industry and among those
      who work in fields treated with 2,4-D, chlordane, propargite, and trifluin. These
      findings may have larger public health implications especially in those areas of
      the country where these pesticides are heavily used and where they may be found
      in the ambient atmosphere.

PMID- 17196585
TI  - Local analgesic efficacy of tramadol following intraplantar injection.
AB  - Several studies have suggested that systemic tramadol, an opioid, can represent a
      valuable treatment in severe pain conditions because of their effects on central
      pain pathways. However, there are not enough studies supporting that tramadol is
      efficacious when administered locally. Therefore, we studied the potential local
      analgesic effects of tramadol in peripheral nociception. In addition, we tested
      the antinociceptive effects of tramadol-CaCl(2) or naloxone combinations after
      subcutaneous intraplantar injection in a validated rat model of acute thermal
      nociception. Local analgesic effects of tramadol were compared with those of
      lidocaine. The effects of tramadol on thermal paw withdrawal latencies were
      monitored using the plantar test. The antinociceptive potency of tramadol is
      higher and long-lasting than that of lidocaine. Naloxone was unable to inhibit
      the increased antinociceptive response produced by tramadol. Ca(2+) modified the
      effect of tramadol. When Ca(2+) dose was increased in the solution, thermal
      antinociceptive potency of tramadol, but not lidocaine was prolonged. Thermal
      nociceptive responses were not affected in the non-injected paws, indicating a
      lack of systemic effects with doses of tramadol and lidocaine that elicited local
      analgesia. These results suggest that intraplantar tramadol administration can
      produce local analgesic effect with a different action mechanism than that of
      lidocaine. In addition, extracellular Ca(2+) may play an important role in the
      local analgesic action of tramadol.

PMID- 17196586
TI  - Dual effect of endothelin 1 on angiotensin II-potentiated purinergic
      neurotransmission in prostatic rat vas deferens.
AB  - Angiotensin and endothelin are vasoactive peptides with neuromodulatory effect,
      however their interactions in facilitating neurotransmission are largely unknown.
      In the present study, effort was made to examine how endothelin 1 modulates
      angiotensin II-potentiated purinergic neurotransmission in prostatic rat vas
      deferens. Both peptides facilitated field-stimulated muscle contraction in a
      concentration-dependent manner with Kd values of 16.97+/-6.47 and 2.46+/-0.83 nM
      for angiotensin II and endothelin 1, respectively. Hill plot analysis gave Hill
      constants of 0.91+/-0.15 and 0.97+/-0.26 for angiotensin II and endothelin 1,
      respectively. Correlation analysis indicated that the extent of potentiation by
      angiotensin II, but not endothelin 1, was proportional to the basal field
      stimulated muscle contraction. In the presence of low concentrations of
      endothelin 1 (< or = 3 nM), angiotensin II-potentiated field-stimulated
      contraction was further enhanced by endothelin. However, in the presence of high
      concentrations of endothelin 1 (> or = 10 nM), a much increased basal field
      stimulated contraction was observed, and the addition of angiotensin II did not
      elicit any further enhancement in the contractile response. Intriguingly, after
      prolonged exposure of prostatic rat vas deferens to a high concentration of
      endothelin 1, the addition of angiotensin II induced a refractory response to
      field-stimulation. Taken together, our result indicated that endothelin 1
      augmented angiotensin II-facilitated purinergic neurotransmission in prostatic
      rat vas deferens at low concentrations, but inhibited gradually at high
      concentrations.

PMID- 17196587
TI  - Transcriptional silencing of glucocorticoid-inducible phenylethanolamine N
      methyltransferase expression by sequential signaling events.
AB  - Specific arrays and timing of environmental cues including glucocorticoids,
      neurotrophic factors and intracellular messengers influence phenotype expression
      in developing chromaffin cells or sympathetic neurons. Although the two lineages
      are closely related, only adrenergic chromaffin cells express phenylethanolamine
      N-methyltransferase (PNMT), the enzyme that synthesizes epinephrine, while
      neurons and noradrenergic chromaffin cells are PNMT-negative. It remains unclear
      to what extent the ability to express PNMT is determined by environmental cues
      versus intrinsic heterogeneity already present in ganglionic and adrenal
      precursors. Mouse pheochromocytoma (MPC) cell lines are a model for studying
      adrenergic differentiation. In two MPC lines that exhibit up to 1000-fold
      induction of PNMT mRNA by dexamethasone, pretreatment with glial cell line
      derived neurotrophic factor (GDNF) and/or the cyclic AMP analog cpt-cAMP markedly
      blunts or abrogates PNMT inducibility. PNMT suppression occurs without apparent
      neuronal differentiation in one of the MPC lines and in normal adult mouse
      chromaffin cell cultures. Our results establish transcriptional suppression by
      cAMP as a mechanism for regulating PNMT expression in both normal and neoplastic
      mouse chromaffin cells. However, contrast between large increases in PNMT mRNA
      levels and low stimulation of promoter activity suggests that modulation of mRNA
      degradation also plays an important role. Clarification of mechanisms that
      regulate these two processes in MPC cells may provide insight into developmental
      mechanisms governing expression and maintenance of the adrenergic phenotype.

PMID- 17196588
TI  - The role of the slug transcription factor in cell migration during corneal re
      epithelialization in the dog.
AB  - Epithelial cell migration during corneal wound re-epithelialization shares
      features with the developmental process of epithelial-mesenchymal transition
      (EMT) modulated by Snail family transcription factors, including Slug. Our
      studies demonstrated that Slug expression was enhanced at sites of epithelial
      cell migration at the margins of normally healing corneal wounds in dogs, but
      significantly decreased at the margins of non-healing canine corneal erosions.
      Increased Slug expression was associated with internalization of E-cadherin and
      beta-catenin from the cell membrane and with enhanced expression of smooth-muscle
      specific alpha-actin, tropomyosin, and matrix metalloproteinases at wound
      margins. Enhanced Slug expression in corneal explants due to an adenoviral
      expression construct or to oxytetracycline treatment resulted in significantly
      higher rates of corneal epithelial cell migration. Oxytetracycline appeared to
      act by stimulating transforming growth factor-beta activity, thus increasing Slug
      expression and enhancing corneal epithelial migration. These findings highlight
      the similarities between epithelial migration during EMT and during successful
      corneal wound healing, support an important role for the Snail family in the
      process, and indicate that modulating Slug expression may be clinically useful in
      treating non-healing corneal wounds.

PMID- 17196589
TI  - Glaucomatous outflow pathway and oxidative stress.
AB  - Oxidative free radicals and reactive oxygen species (ROS) are able to affect the
      cellularity of the human trabecular meshwork (HTM). These findings suggest that
      intraocular pressure increase, which characterises most glaucomas, is related to
      oxidative degenerative processes affecting the HTM and specifically its
      endothelial cells. Much evidence indicates that in this region ROS play a
      fundamental pathogenic role by reducing local antioxidant activities, inducing
      outflow resistance and exacerbating the activities of superoxide dismutase and
      glutathione peroxidase in glaucomatous eyes. Furthermore, hydrogen peroxide
      induces rearrangement of HTM cells and compromises their integrity. Glaucomatous
      subjects might have a genetic predisposition rendering them more susceptible to
      ROS-induced damage. A fairly significant correlation between oxidative DNA damage
      in the HTM and intraocular pressure increase and visual field defects in
      glaucomatous patients has been demonstrated. Thus, oxidative stress may play a
      significant role during glaucoma course initially damaging HTM cells, then
      contributing to the alteration of the homeostasis between NO and endothelins, and
      finally through its possible involvement in ganglional cell death. On the whole,
      these findings support the hypothesis that oxidative damage is an important step
      in the pathogenesis of primary open-angle glaucoma, and might be a relevant
      target for both prevention and therapy.

PMID- 17196590
TI  - Pharmacological activation of mGlu2/3 metabotropic glutamate receptors protects
      retinal neurons against anoxic damage in the goldfish Carassius auratus.
AB  - We examined the expression of mGlu2/3 metabotropic glutamate receptors in the
      retina of the goldfish Carassius auratus. mGlu2/3 receptors were expressed in all
      retinal layers internal to the photoreceptor layer, particularly in the outer and
      inner nuclear layers. Although the goldfish brain is able to tolerate prolonged
      periods of anoxia, we examined whether anoxia could induce retinal damage. Three
      hours of anoxia induced in the retina the development of apoptotic cell death, as
      assessed 48 h later by TUNEL staining. TUNEL-positive cells were particularly
      found in the inner and outer nuclear layers, and were also present in the
      ganglion cell layer. Pharmacological activation of mGlu2/3 receptors by systemic
      injection of LY379268 (0.5 mg/kg, i.p., 15 min before the onset of anoxia)
      substantially protected retinas against anoxia-induced cell death. In contrast,
      systemic injection of the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.,
      15 min before the onset of anoxia), significantly amplified cell death. Finally,
      as mGlu2/3 receptors are implicated in the control of extracellular glutamate
      concentrations, we examined the stimulation of glutamate release in isolated
      goldfish retinas. Depolarizing medium containing 30 mM KCl led to a significant
      increase in glutamate release, which was substantially reduced by LY379268. We
      conclude that activation of mGlu2/3 receptors may provide a major defensive
      mechanism against ischemic/anoxic retinal damage.

PMID- 17196591
TI  - A new approach to preserve fertility by using a coated nitinol stent in a patient
      with recurrent cervical stenosis.
AB  - OBJECTIVE: The incidence of hematometra caused by cervical stenosis after
      conization is <1%. Nevertheless, if dilatation was unsuccessful, further therapy
      often remains unclear, and the clinical consequences can be severe, including
      hysterectomy. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 33
      year old patient who developed recurrent cervical stenosis with consecutive
      hematometra after two conizations during lactation amenorrhea that could not be
      treated by dilatation and insertion of a temporary plastic catheter according to
      the manufacturer's instructions. INTERVENTION(S): Insertion of a coated nitinol
      stent in the cervical canal after dilatation and hysteroscopic removal of the
      hematometra. MAIN OUTCOME MEASURE(S): Normal menstruation, future pregnancy.
      RESULT(S): The patient was free of symptoms, had a normal menstruation, and has
      become pregnant. CONCLUSION(S): The insertion of a coated vessel stent in the
      uterine cervix appears to be a valid alternative in patients with recurrent
      cervical stenosis and hematometra after conization to preserve childbearing
      function.

PMID- 17196592
TI  - Testosterone levels in women and men who are single, in long-distance
      relationships, or same-city relationships.
AB  - Research points to an association between testosterone (T) and partnering in some
      women and men, and this association has been interpreted as an effect of either
      relationship status (i.e. differences in relationship status lead to differences
      in T) or relationship orientation (i.e. T is associated with the likelihood of
      entering relationships). To address whether physical partner presence was
      associated with decreased T, we examined T levels in people (72 women; 49 men)
      who were single, in long-distance relationships, or in same-city relationships.
      No participants were using exogenous hormones, including hormonal contraceptives.
      Participants provided a saliva sample and responded to questions about their
      relationship status. Single men had higher T than long-distance and same-city
      partnered men, which supports the relationship orientation interpretation. In
      contrast, same-city partnered women had lower T than single women and women in
      long-distance relationships, which supports the relationship status
      interpretation. We conclude that physical partner presence is not necessary to
      see an association between partnering and hormones in men (since same-city and
      long-distance partnered men had similar T levels), but may be necessary in women
      (since same-city partnered women had lower T than long-distance partnered women).

PMID- 17196593
TI  - Expression of Eph B4 and Ephrin B2 in cervical cancer tissues and angiogenesis.

PMID- 17196594
TI  - Conservation of CD4+ T cell-dependent developmental mechanisms in the blood fluke
      pathogens of humans.
AB  - Schistosoma blood flukes are trematode parasites with a cosmopolitan distribution
      that infect over 200 million people globally. We previously showed that
      Schistosoma mansoni growth and development in the mammalian host is dependent on
      signals from host CD4+ T cells. To gain insight into the mechanisms that underlie
      this dependence, we sought to determine the evolutionary origins and limits of
      this aspect of the host-pathogen relationship. By infecting RAG-1-/- mice with a
      range of different schistosome species and strains, we tested several hypotheses
      concerning the time during Schistosoma evolution at which this dependence arose,
      and whether this dependence is specific to Schistosoma or is also found in other
      blood flukes. Our data indicate that the developmental dependence on CD4+ T cells
      previously described for S. mansoni is conserved in the evolutionarily basal
      species Schistosoma japonicum, suggesting this developmental adaptation arose
      early in Schistosoma evolution. We also demonstrate that the development of the
      more evolutionarily derived species Schistosoma haematobium and Schistosoma
      intercalatum are dependent on adaptive immune signals. Together, these data
      suggest that the blood fluke parasites of humans utilise common mechanisms to
      infect their hosts and to co-opt immune signals in the coordination of parasite
      development. Thus, exploitation of host-schistosome interactions to impair or
      prevent parasite development may represent a novel approach to combating all of
      the schistosome pathogens of humans.

PMID- 17196595
TI  - Identification of basic transcriptional elements required for rif gene
      transcription.
AB  - The rif gene family is the largest multi-gene family in the malaria parasite
      Plasmodium falciparum. The gene products of rif genes, rifins, are clonally
      variant and transported to the surface of the infected erythrocyte where they are
      targets of the human immune response. Maximal rif transcription occurs during the
      late ring to early trophozoite stages of the intra-erythrocytic cycle. The
      factors involved in the transcriptional activation and repression of rif genes
      are not known. In this paper, we characterize several DNA elements involved in
      the regulation of rif transcription. We identify the upstream region that
      contains a functional promoter and the transcriptional start site of a rif gene.
      In addition, we identify two distinct regions within the rif upstream region
      involved in the transcriptional repression of these genes. These repressor sites
      are bound by nuclear protein factors expressed in different stages of the
      Plasmodium life cycle. We propose that the differential timing of binding
      provides a mechanism for the temporal repression of rif genes. In addition, we
      find that transcription profiles of upsA var genes and their neighbouring rif
      genes are unlinked.

PMID- 17196596
TI  - The scaling of total parasite biomass with host body mass.
AB  - The selective pressure exerted by parasites on their hosts will to a large extent
      be influenced by the abundance or biomass of parasites supported by the hosts.
      Predicting how much parasite biomass can be supported by host individuals or
      populations should be straightforward: ultimately, parasite biomass must be
      controlled by resource supply, which is a direct function of host metabolism.
      Using comparative data sets on the biomass of metazoan parasites in vertebrate
      hosts, we determined how parasite biomass scales with host body mass. If the rate
      at which host resources are converted into parasite biomass is the same as that
      at which host resources are channelled toward host growth, then on a log-log plot
      parasite biomass should increase with host mass with a slope of 0.75 when
      corrected for operating temperature. Average parasite biomass per host scaled
      with host body mass at a lower rate than expected (across 131 vertebrate species,
      slope=0.54); this was true independently of phylogenetic influences and also
      within the major vertebrate groups separately. Since most host individuals in a
      population harbour a parasite load well below that allowed by their metabolic
      rate, because of the stochastic nature of infection, it is maximum parasite
      biomass, and not average biomass, that is predicted to scale with metabolic rate
      among host species. We found that maximum parasite biomass scaled isometrically
      (i.e., slope=1) with host body mass. Thus, larger host species can potentially
      support the same parasite biomass per gram of host tissues as small host species.
      The relationship found between maximum parasite biomass and host body mass, with
      its slope greater than 0.75, suggests that parasites are not like host tissues:
      they are able to appropriate more host resources than expected from metabolically
      derived host growth rates.

PMID- 17196598
TI  - Associations between connexin37 gene polymorphism and markers of subclinical
      atherosclerosis: the Cardiovascular Risk in Young Finns study.
AB  - OBJECTIVE: Connexin37 (cx37) C1019T polymorphism has been shown to associate with
      coronary artery disease in different populations. We investigated whether this
      polymorphism associates with carotid artery intima-media thickness (IMT), carotid
      artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) -
      i.e., early ultrasound markers of subclinical atherosclerosis - in a clinically
      healthy population of young Finnish adults. METHODS AND RESULTS: 1440 individuals
      from the Cardiovascular Risk in Young Finns study were genotyped and studied
      using cardiovascular risk factor and ultrasound data obtained in 2001. In linear
      regression models, no significant association between the cx37 polymorphism and
      carotid IMT, CAC or brachial artery FMD (ANOVA, p=0.159, 0.151 and 0.547),
      respectively, was found in the whole population or in women and men separately.
      CONCLUSIONS: The connexin37 C1019T polymorphism is not related with markers of
      subclinical atherosclerosis in young adults.

PMID- 17196597
TI  - Gene silencing of the tick protective antigens, Bm86, Bm91 and subolesin, in the
      one-host tick Boophilus microplus by RNA interference.
AB  - The use of RNA interference (RNAi) to assess gene function has been demonstrated
      in several three-host tick species but adaptation of RNAi to the one-host tick,
      Boophilus microplus, has not been reported. We evaluated the application of RNAi
      in B. microplus and the effect of gene silencing on three tick-protective
      antigens: Bm86, Bm91 and subolesin. Gene-specific double-stranded (dsRNA) was
      injected into two tick stages, freshly molted unfed and engorged females, and
      specific gene silencing was confirmed by real time PCR. Gene silencing occurred
      in injected unfed females after they were allowed to feed. Injection of dsRNA
      into engorged females caused gene silencing in the subsequently oviposited eggs
      and larvae that hatched from these eggs, but not in adults that developed from
      these larvae. dsRNA injected into engorged females could be detected by
      quantitative real-time RT-PCR in eggs 14 days from the beginning of oviposition,
      demonstrating that unprocessed dsRNA was incorporated in the eggs. Eggs produced
      by engorged females injected with subolesin dsRNA were abnormal, suggesting that
      subolesin may play a role in embryonic development. The injection of dsRNA into
      engorged females to obtain gene-specific silencing in eggs and larvae is a novel
      method which can be used to study gene function in tick embryogenesis.

PMID- 17196601
TI  - Comparison of the reliability of the identification with diode array detector and
      mass spectrometry.
AB  - The reliability of compound identification by low resolution mass spectrometry
      (MS) was quantitatively compared with that for diode array detection (DAD). The
      quantity of the information obtained with one parent ion and two characteristic
      daughter ions at low resolution MS-MS was compared with that obtained by UV-vis
      spectra with large wavelength range from DAD. It was shown that if the UV-vis
      spectra are reproducible, i.e. with low RSD values for selected wavelengths and
      relative absorption, the reliability of the identification with DAD is comparable
      with the one for low resolution MS-MS. Because the sensitivity of the DAD is one
      or two orders of magnitude lower than that of mass spectrometry, on-column
      focusing was applied and reliable identification was achieved at 1 ppb
      concentration. The surprisingly high reliability of identification obtained with
      contemporary DADs should increase the analysts' confidence in this method of
      detection/confirmation.

PMID- 17196600
TI  - Optimizing refolding and recovery of active recombinant Bacillus halodurans
      xylanase in polymer-salt aqueous two-phase system using surface response
      analysis.
AB  - An experimental design was used to determine optimal conditions for refolding of
      a recombinant thermostable and alkaline active xylanase from Bacillus halodurans
      in PEG-phosphate two-phase system. The influence of different experimental
      variables on the enzyme recovery has been evaluated. To build the mathematical
      model and minimize the number of experiments for the design parameters, response
      surface methodology with a face-centered central composite design (CCF) was
      defined based on the conditions found by preliminary tests that resulted in the
      highest refolding yield. The adequacy of the calculated model for the response
      was confirmed by means of variance analysis and additional experiments. Analysis
      of contours of constant response as a function of pH, polyethylene glycol (PEG)
      molecular weight and concentration, and salt concentration for different enzyme
      loads revealed different effects of these five factors on the studied parameters.
      Recovery of more than 92% active xylanase was predicted for a system with 18.3%
      (w/w) PEG 1000, 14.4% (w/w) phosphate at pH 8.5, and enzyme load corresponding to
      a protein concentration of about 0.05 mg/g system. The yield of the refolded
      enzyme was found to be optimal at 22 degrees C. The validity of the response
      model was verified by a good agreement between predicted and experimental
      results.

PMID- 17196602
TI  - Modelling the adsorption of Cd(II), Cu(II), Ni(II), Pb(II), and Zn(II) onto
      Fithian illite.
AB  - Illite samples from Fithian, IL were purified and saturated with Na(+) ions. The
      acid-base surface chemistry of the Na-saturated illite was studied by
      potentiometric titration experiments with 0.1, 0.01, and 0.001 M NaNO(3)
      solutions as the background electrolyte. Results showed that the titration curves
      obtained at different ionic strengths did not intersect in the studied pH range.
      The adsorption of Cd(II), Cu(II), Ni(II), Pb(II), and Zn(II) onto illite was
      investigated as a function of pH and ionic strength by batch adsorption
      experiments. Two distinct mechanisms of metal adsorption were found from the
      experimental results: nonspecific ion-exchange reactions at lower pH values on
      the basal surfaces and 'frayed edges' and specific adsorption at higher pH values
      on the mineral edges. Ionic strength had a greater effect on the ion-exchange
      reactions. The binding constants for the five heavy metals onto illite were
      determined using the least-square fitting computer program FITEQL. Linear free
      energy relationships were found between the surface binding constants and the
      first hydrolysis constants of the metals.

PMID- 17196599
TI  - Intrinsic mechanical properties of trabecular calcaneus determined by finite
      element models using 3D synchrotron microtomography.
AB  - To determine intrinsic mechanical properties (elastic and failure) of trabecular
      calcaneus bone, chosen as a good predictor of hip fracture, we looked for the
      influence of image's size on a numerical simulation. One cubic sample of
      cancellous bone (9 x 9 x 9 mm(3)) was removed from the body of the calcaneus (6
      females, 6 males, 79+/-9 yr). These samples were tested under compressive
      loading. Before compressive testing, these samples were imaged at 10.13 microm
      resolution using a 3D microcomputed tomography (muCT) (ESRF, France). The muCT
      images were converted to finite-element models. Depending on the bone density
      values (BV/TV), we compared two different finite element models: a linear
      hexahedral and a linear beam finite element models. Apparent experimental Young's
      modulus (E(app)(exp)) and maximum apparent experimental compressive stress
      (sigma(max)(exp)) were significantly correlated with bone density obtained by
      Archimedes's test (E(app)(exp)=236+/-231 MPa [19-742 MPa], sigma(max)(exp)=2.61+/
      1.97 MPa [0.28-5.81 MPa], r>0.80, p<0.001). Under threshold at 40 microm, the
      size of the numerical samples (5.18(3) and 6.68(3)mm(3)) seems to be an important
      parameter on the accuracy of the results. The numerical trabecular Young's
      modulus was widely higher (E(trabecular)(num)=34,182+/-22,830 MPa [9700-87,211
      MPa]) for the larger numerical samples and high BV/TV than those found
      classically by other techniques (4700-15,000 MPa). For rod-like bone samples
      (BV/TV<12%, n=7), Young's modulus, using linear beam element (E(trabecular)(num
      skeleton): 10,305+/-5500 MPa), were closer to the Young's modulus found by other
      techniques. Those results show the limitation of hexahedral finite elements at 40
      microm, mostly used, for thin trabecular structures.

PMID- 17196603
TI  - Poly(N-isopropylacrylamide) nanocrosslinked by polyhedral oligomeric
      silsesquioxane: temperature-responsive behavior of hydrogels.
AB  - Octa(propylglycidyl ether) polyhedral oligomeric silsesquioxane (OpePOSS) was
      used as a nanocrosslinking agent to prepare the crosslinked poly(N
      isopropylacrylamide) (PNIPAM) networks with POSS content up to 50 wt%. The inter
      component crosslinking was achieved via the reaction between NH moieties in amide
      group of PNIPAM and epoxide groups of OpePOSS. When the organic-inorganic
      nanocomposites were swollen in water the POSS-crosslinked PNIPAM exhibited the
      characteristics of hydrogels. With the moderate contents of POSS, the POSS
      containing hybrid hydrogels displayed much faster response rates in swelling,
      deswelling and reswelling experiments than the PNIPAM hydrogels prepared via the
      free radical copolymerization of N-isopropylacrylamide (NIPAM) and N,N(')
      methylenebisacrylamide (viz. the conventional crosslinker). The improved hydrogel
      properties have been interpreted on the basis of the formation of the nanosized
      hydrophobic microdomains around the POSS moieties (i.e., the nanocrosslinking
      sites).

PMID- 17196604
TI  - Removal of Reactofix Navy Blue 2 GFN from aqueous solutions using adsorption
      techniques.
AB  - The wheat husk, an agricultural by-product, has been activated and used as an
      adsorbent for the adsorption of Reactofix Navy Blue 2 GFN from aqueous solution.
      In this work, adsorption of Reactofix Navy Blue 2 GFN on wheat husk and charcoal
      has been studied by using batch studies. The equilibrium adsorption level was
      determined to be a function of the solution pH, adsorbent dosage, dye
      concentration and contact time. The equilibrium adsorption capacities of wheat
      husk and charcoal for dye removal were obtained using Freundlich and Langmuir
      isotherms. Thermodynamic parameters such as the free energies, enthalpies and
      entropies of adsorption were also evaluated. Adsorption process is considered
      suitable for removing color, COD from waste water.

PMID- 17196605
TI  - Effect of a new hydrophobically modified polyampholyte on the formation of
      inverse microemulsions and the preparation of gold nanoparticles.
AB  - A new regular polyampholyte, namely poly-(N,N-dially-N,N-dimethylammonium-alt-N
      octyl-maleamic carboxylate), was synthesized by alternating free radical
      copolymerization. The influence of the added polymer on the range of the inverse
      micellar region (L(2) phase) of a SDS-based system was investigated. The phase
      behavior as well as conductivity measurements indicate that the polymer, which
      forms hydrophobic microdomains, is located more in the water core of the
      microemulsion droplets rather than at the interface of the surfactant film. The
      polyampholyte proved to be an efficient reducing and stabilizing agent for the
      formation of gold colloids. The process of nanoparticle formation was
      investigated in the absence of any other reducing agent, in water as well as in
      the microemulsion template phase. In both cases, nanoscalic gold particles can be
      synthesized, while the adsorption of the polymer on the particle surface prevents
      their aggregation due to electrosteric stabilization.

PMID- 17196606
TI  - Citrate-assisted synthesis of prickly nickel microwires and their surface
      modification with silver.
AB  - A new type of prickly nickel microwires assembled by thornlike nanocrystals was
      fabricated through a simple chemical reduction route with the assistance of
      citrate. Thus-prepared nickel wires were subsequently morphology-retained
      modified with a thin silver shell via transmetallation. Compared with the
      uncoated sample, the Ni(core)-Ag(shell) wires exhibited much-enhanced oxidation
      resistance, slightly changed magnetic properties and stark different catalysis
      for the creation of carbon particles in pyrolyzing acetone.

PMID- 17196607
TI  - Facile fabrication of long alpha-Fe(2)O(3), alpha-Fe and gamma-Fe(2)O(3) hollow
      fibers using sol-gel combined co-electrospinning technology.
AB  - Long alpha-Fe(2)O(3) hollow fibers have been prepared through a facile sol-gel
      combined co-electrospinning technique using ferric citrate as precursor, and
      alpha-Fe and gamma-Fe(2)O(3) hollow fibers have been obtained by reduction and
      reoxidation at different conditions. The outer diameter of the as-prepared hollow
      fibers is 0.5-5 microm with wall thickness of 200-800 nm. The obtained tubular
      fibers were characterized by thermal gravimetric (TG), FT-IR spectra, X-ray
      diffraction (XRD), transmission electron microscopy (TEM), scanning electron
      microscopy (SEM) and Raman techniques. In addition, magnetic properties of alpha
      Fe and gamma-Fe(2)O(3) hollow fibers have also been investigated.

PMID- 17196608
TI  - Rheology of double emulsions.
AB  - New equations for the viscosity of concentrated double emulsions of core-shell
      droplets are developed using a differential scheme. The equations developed in
      the paper predict the relative viscosity (eta(r)) of double emulsions to be a
      function of five variables: a/b (ratio of core drop radius to shell outer
      radius), lambda(21) (ratio of shell liquid viscosity to external continuous phase
      viscosity), lambda(32) (ratio of core liquid viscosity to shell liquid
      viscosity), phi(DE) (volume fraction of core-shell droplets in double emulsion),
      and phi(m)(DE) (the maximum packing volume fraction of un-deformed core-shell
      droplets in double emulsion). Two sets of experimental data are obtained on the
      rheology of O/W/O (oil-in-water-in-oil) double emulsions. The data are compared
      with the predictions of the proposed equations. The proposed equations describe
      the experimental viscosity data of double emulsions reasonably well.

PMID- 17196609
TI  - Kinetic and isothermal studies of lead ion adsorption onto palygorskite clay.
AB  - The use of a natural palygorskite clay for the removal of Pb(II) from aqueous
      solutions for different contact times, pHs of suspension, and amounts and
      particle sizes of palygorskite clay were investigated. The variations of the pH
      value of Pb(II) solutions on natural palygorskite in the adsorption process were
      determined. Batch adsorption kinetic experiments revealed that the adsorption of
      Pb(II) onto palygorskite clay involved fast and slow processes. It was found that
      the adsorption mechanisms in the lead/palygorskite system follow pseudo-second
      order kinetics with a significant contribution from film diffusion. SEM
      observations demonstrated that an important interaction at the lead-granule
      interface occurred during the adsorption process. The adsorption isotherms were
      described by means of the Langmuir and Freundlich isotherms and the Langmuir
      model represents the adsorption process better than the Freundlich model. The
      maximum adsorption capacity of Pb(II) onto natural palygorskite was 104.28 mg g(
      1).

PMID- 17196610
TI  - On mixed binary surfactant systems comprising MEGA 10 and alkyltrimethylammonium
      bromides: a detailed physicochemical study with a critical analysis.
AB  - Self-aggregation of mixed binary nonionic and ionic surfactants comprising N
      methyl-N-decanoyl glucamide (MEGA 10) and alkyltrimethylammonium bromides (C(12)
      , C(14)-, and C(16)TAB) has been investigated in detail by different physical
      methods. The counter-ion binding, aggregation number, and polarity of the mixed
      micelles have been determined. The results have been analyzed in the light of the
      theories of Rubingh and Maeda. The thermodynamic parameters of the micellization
      process have been evaluated and discussed. The interfacial adsorptions of the
      mixed amphiphiles including their surface excesses and head-group areas have also
      been evaluated. Based on the head-group areas, the overall shapes of the mixed
      micelles have been predicted from the estimation of the amphiphile packing
      parameters.

PMID- 17196611
TI  - Thermal stability of the WHO international standard of interferon alpha 2b (IFN
      alpha 2b): application of new reporter gene assay for IFN-alpha 2b potency
      determinations.
AB  - A World Health Organization requirement for biological standards is that they
      should exhibit long-term stability at their recommended storage temperature.
      Thermal stability is usually predicted in accelerated thermal degradation
      studies, where ampoules of the lyophilized standard are stored at elevated
      temperatures for relatively short times before testing. To confirm the predicted
      thermal stability of the 2nd international standard of human interferon alpha 2b
      (IFN-alpha2b; 95/566), we tested the potency of the ampouled contents of this
      standard after 9 years storage at the customary storage temperature of -20
      degrees C in comparison with ampoules of the IS which had been stored
      continuously at temperatures ranging from -150 degrees C to 56 degrees C. Since
      IFN-alpha2b potency estimates derived from the results of antiviral assays (AVA)
      showed high within-assay variability, we investigated a novel reporter gene assay
      (RGA) based on induction of secreted alkaline phosphatase (SEAP) for
      comparability and precision of such estimations. We show that this RGA generated
      comparable estimates with overall lower variation. Additionally, the SEAP
      conversion of p-nitrophenyl phosphate to yellow product could be followed
      kinetically. Absorbance readings were shown to increase with time in proportion
      with increasing concentration of IFN-alpha2b. When the time-dependent increments
      of absorbance were plotted graphically, the slopes of lines corresponded to
      concentration. This approach enabled single dilutions of IFN samples, identical
      in molecular structure to an IFN-alpha2b standard, to be used for potency
      estimates by interpolation of slope value against those of the standard at fixed
      concentrations. It appears attractive for high through-put potency testing of
      various R&D IFN-alpha2b samples.

PMID- 17196612
TI  - Structure and putative function of dark- and light-adapted as well as UV-exposed
      eyes of the food store pest Psyllipsocus ramburi Selys-longchamps (Insecta:
      Psocoptera: Psyllipsocidae).
AB  - The psocopteran Psyllipsocus ramburi Selys-Longchamps can render food stuffs
      unpalatable and may serve as an intermediate host for cestodes. Its two circular
      compound eyes consist of about 26 facets, capped by strongly convexly curved
      corneae of 10-18 microm in diameter. Corneal nipples or interommatidial hairs are
      not developed. Beneath each corneal lens a cluster of four cone cells, enveloped
      by two primary pigment cells, separates an ommatidial group of eight retinula
      cells from the inner corneal surface. Membrane specializations of the retinula
      cells, known as the microvilli, measure 60 nm in diameter, and collectively make
      up the rhabdom, which is columnar in shape and has a distal diameter of 4 or 5
      microm, depending on whether it is day- or night-adapted. Cone cell lengths
      measure 4.5 microm during the day and 8.5 microm at night and retinula cell
      screening pigments closely approach the edge of the rhabdom during the day. A 1-h
      exposure to UV-A (lambda(max)=351 nm) of ca. 1200 lx causes an almost total
      destruction of the photoreceptive membranes of the rhabdom and bleached all
      retinula cell screening pigments, but not the pigment grains of the primary
      pigment cells. Calculations, based on the anatomical data, suggest that the eyes
      are adapted to function under dim light levels, but cannot produce sharp images
      since their best possible acceptance angles are 22 degrees and 28 degrees in
      light- and dark-adapted states, respectively. Destruction of vision, likely
      affecting biorhythm and reproduction, by exposing the insects to UV-A may offer
      an alternative to the use of chemicals in controlling these insects.

PMID- 17196614
TI  - MYBBP1a is a novel repressor of NF-kappaB.
AB  - NF-kappaB is an inducible transcription factor activated in many different cell
      types by inflammatory and stress signals. The transcription of a wide variety of
      NF-kappaB genes is regulated by the coordinated action of transcription co
      activators and co-repressors. Previously we identified Myb binding protein 1a
      (MYBBP1a) as an interaction partner of the transcription activation domain of
      RelA/p65. MYBBP1a has been shown by others to regulate various transcription
      factors, through largely unknown mechanisms. Here we present evidence that
      MYBBP1a is a novel co-repressor of NF-kappaB. MYBBP1a interacted directly with
      RelA/p65 and expression of MYBBP1a in cells repressed NF-kappaB dependent
      reporter expression but did affect neither RelA/p65 nuclear translocation nor its
      DNA binding activity. In vitro, MYBBP1a inhibited transcription from
      chromatinized templates at a step before pre-initiation complex formation.
      MYBBP1a was found to compete with the histone acetyl transferase co-activator,
      p300, for interaction with the transcription activation domain of RelA/p65.
      Expression levels of MYBBP1a are dependent on the cell type, and are particularly
      high in Jurkat T cells. These results indicate that MYBBP1a is a novel NF-kappaB
      co-repressor of transcription that competes with p300 and may function to
      regulate cell type specific genes.

PMID- 17196613
TI  - A Caveat Emptor for myocardial regeneration: mechanical without electrical
      recovery will not suffice.

PMID- 17196615
TI  - Crystallographic study of the tetrabutylammonium block to the KcsA K+ channel.
AB  - K(+) channels play essential roles in regulating membrane excitability of many
      diverse cell types by selectively conducting K(+) ions through their pores. Many
      diverse molecules can plug the pore and modulate the K(+) current. Quaternary
      ammonium (QA) ions are a class of pore blockers that have been used for decades
      by biophysicists to probe the pore, leading to important insights into the
      structure-function relation of K(+) channels. However, many key aspects of the QA
      blocking mechanisms remain unclear to date, and understanding these questions
      requires high resolution structural information. Here, we address the question of
      whether intracellular QA blockade causes conformational changes of the K(+)
      channel selectivity filter. We have solved the structures of the KcsA K(+)
      channel in complex with tetrabutylammonium (TBA) and tetrabutylantimony (TBSb)
      under various ionic conditions. Our results demonstrate that binding of TBA or
      TBSb causes no significant change in the KcsA structure at high concentrations of
      permeant ions. We did observe the expected conformational change of the filter at
      low concentration of K(+), but this change appears to be independent of TBA or
      TBSb blockade.

PMID- 17196616
TI  - Lysozyme amyloidogenesis is accelerated by specific nicking and fragmentation but
      decelerated by intact protein binding and conversion.
AB  - We have revisited the well-studied heat and acidic amyloid fibril formation
      pathway (pH 1.6, 65 degrees C) of hen egg-white lysozyme (HEWL) to map the
      barriers of the misfolding and amyloidogenesis pathways. A comprehensive kinetic
      mechanism is presented where all steps involving protein hydrolysis,
      fragmentation, assembly and conversion into amyloid fibrils are accounted for.
      Amyloid fibril formation of lysozyme has multiple kinetic barriers. First, HEWL
      unfolds within minutes, followed by irreversible steps of partial acid hydrolysis
      affording a large amount of nicked HEWL, the 49-101 amyloidogenic fragment and a
      variety of other species over 5-40 h. Fragmentation forming the 49-101 fragment
      is a requirement for efficient amyloid fibril formation, indicating that it forms
      the rate-determining nucleus. Nicked full-length HEWL is recruited efficiently
      into amyloid fibrils in the fibril growth phase or using mature fibrils as seeds,
      which abolished the lag phase completely. Mature amyloid fibrils of HEWL are
      composed mainly of nicked HEWL in the early equilibrium phase but go through a
      "fibril shaving" process, affording fibrils composed of the 49-101 fragment and
      53-101 fragment during more extensive maturation (incubation for longer than ten
      days). Seeding of the amyloid fibril formation process using sonicated mature
      amyloid fibrils accelerates the fibril formation process efficiently; however,
      addition of intact full-length lysozyme at the end of the lag phase slows the
      rate of amyloidogenesis. The intact full-length protein, in contrast to nicked
      lysozyme, slows fibril formation due to its slow conversion into the amyloid
      fold, probably due to inclusion of the non-amyloidogenic 1-48/102-129 portion of
      HEWL in the fibrils, which can function as a "molecular bumper" stalling further
      growth.

PMID- 17196617
TI  - The role of LRP and H-NS in transcription regulation: involvement of synergism,
      allostery and macromolecular crowding.
AB  - LRP has recently been shown to interact with the regulatory regions of bacterial
      ribosomal RNA promoters. Here we study details of the LRP-rDNA interaction by gel
      retardation and high-resolution footprinting techniques. We show that a second
      regulator for rRNA transcription, H-NS, facilitates the formation of a higher
      order LRP-nucleoprotein complex, probably acting transiently as a DNA chaperone.
      The macromolecular crowding substance ectoine stabilizes the formation of this
      dynamic complex, while the amino acid leucine, as a metabolic effector, has the
      opposite effect. DNase I and hydroxyl radical footprint experiments with LRP-DNA
      complexes reveal a periodic change of the target DNA structure, which implies
      extensive DNA wrapping reaching into the promoter core region. We show
      furthermore that LRP binding is able to constrain supercoils, providing a link
      between DNA topology and regulation. The results support the conclusion that the
      bacterial DNA-binding protein LRP, assisted by H-NS, forms a repressive
      nucleoprotein structure involved in regulation of rRNA transcription. The
      formation of this regulatory structure appears to be directly affected by
      environmental changes.

PMID- 17196619
TI  - Decreased capillarization and a shift to fast myosin heavy chain IIx in the
      biceps brachii muscle from young adults with spastic paresis.
AB  - Muscle spasticity and paresis are conditions that occur secondary to upper motor
      neuron lesions. The co-existence of decreased motor unit recruitment and
      intermittent over-activity generates confusion concerning the effect on muscle
      fiber characteristics. In order to increase the knowledge about the effect of
      upper motor lesion on capillarization and muscle fiber composition, the biceps
      brachii muscle from seven young adults with long duration of spastic paresis and
      seven age-matched controls were analyzed using morphological and enzyme- and
      immuno-histochemical techniques. The spastic muscles had a 38% lower capillary
      density (p=0.002), 30% fewer capillaries around each muscle fiber (p=0.02), and
      16% fewer capillaries when related to the fiber size (p=0.04). The frequency of
      fibers expressing myosin heavy chain (MyHC) IIx increased (30% vs. 4%, p=0.006),
      while the percentage of fibers expressing MyHC I and MyHC IIa, respectively,
      decreased (22% vs. 46% and 7% vs. 29%, p<0.01). The high proportion of muscle
      fibers with low oxidative capacity and low capillary supply indicates that biceps
      brachii muscle from patients with upper motor lesions fatigue more easily than
      normal controls. We also observed a significantly higher variability in fiber
      size for fibers expressing MyHC I (p<0.04), and, in three of the subjects, a
      small amount of small fibers expressing developmental MyHCs was found. These
      results suggest that, although intermittent stretch reflex contractions might
      have an impact on the muscle characteristics in spastic paresis, the muscle
      phenotypic properties are more adapted to decreased voluntary motor unit
      recruitment.

PMID- 17196618
TI  - Expression of GATA-1 in a non-hematopoietic cell line induces beta-globin locus
      control region chromatin structure remodeling and an erythroid pattern of gene
      expression.
AB  - GATA-1 is a hematopoietic transcription factor expressed in erythroid,
      megakaryocytic, mast cell and eosinophil lineages. It is required for normal
      erythroid differentiation, the expression of erythroid-specific genes and for the
      establishment of an active chromatin structure throughout the beta-globin gene
      locus. GATA-1 is also necessary for the formation and function of the locus
      control region DNase I hypersensitive site (HS) core elements. To determine
      whether GATA-1 was sufficient to direct formation of the locus control region
      (LCR) and an erythroid pattern of gene expression, we expressed GATA-1 in the non
      hematopoietic HeLa cell line that does not express other hematopoietic
      transcription factors but does express GATA-2, GATA-3, and GATA-6. We found that
      production of the GATA-1 protein resulted in the formation of LCR DNase I HSs 1-4
      in their normal locations, and that histones became hyperacetylated within these
      regulatory elements. Transcription of several erythroid-specific genes was
      activated in HeLa cells expressing GATA-1, including those coding for alpha
      globin, beta-globin, the erythropoietin receptor, the erythroid krupple-like
      factor and p45 NF-E2. Despite increased expression of these genes at the mRNA
      level, their protein products were not detected. These results imply that GATA-1
      is sufficient to direct chromatin structure reorganization within the beta-globin
      LCR and an erythroid pattern of gene expression in the absence of other
      hematopoietic transcription factors.

PMID- 17196620
TI  - A unique episode of REM sleep behavior disorder triggered during surgery for
      Parkinson's disease.
AB  - REM sleep behavior disorder (RBD) is characterized by vigorous movements during
      REM sleep. Here, the authors report the case of a patient who presented such a
      disorder immediately after the implantation of the definitive electrode for left
      subthalamic stimulation. Interestingly, this was and has remained a unique
      episode in his medical history. It was found that a microlesion in or near the
      upper part of the pars compacta of the substantia nigra was very likely
      responsible for this phenomenon.

PMID- 17196621
TI  - Genetic polymorphism of the angiotensin converting enzyme and L-dopa-induced
      adverse effects in Parkinson's disease.
AB  - There was increasing evidence suggesting that angiotensin I-converting enzyme may
      play an important role in the pathogenesis of PD. Our former study has shown that
      angiotensin I-converting enzyme gene (ACE) may confer a susceptibility for the
      risk of Parkinson's disease (PD). Meanwhile, recent studies have emphasized that
      genetic factors may involve in the occurrence of the adverse effects of chronic L
      dopa therapy in PD patients. This study was designed to assess whether genetic
      polymorphism of the ACE could be a predictor of L-dopa-induced adverse effects in
      PD. There were 251 patients included in this study and their mean age at onset of
      disease was 63.3+/-11.4 years. The duration of disease and the treatment with L
      dopa was 6.3+/-5.1 and 5.0+/-4.3 years, respectively. The frequency of the
      homozygote ACE-II genotype of the ACE in PD patients with L-dopa-induced
      psychosis was significantly higher than that in PD patients without the adverse
      effect (63.3% vs 43.0%; chi(2)=6.347, OR=1.435, 95%CI=1.105-1.864, p=0.012).
      However, the ACE polymorphism was not associated with the risk to develop
      dyskinesia or motor fluctuation induced by L-dopa. Furthermore, a logistic
      regression analysis confirmed that the ACE-II genotype was an independent risk
      factor for L-dopa-induced psychosis in PD patients (OR=2.542, p=0.012). In
      conclusion, results of the study showed that ACE-II genotype might confer a
      primary predictor for the occurrence of psychosis in L-dopa-treated PD.

PMID- 17196622
TI  - Active spice-derived components can inhibit inflammatory responses of adipose
      tissue in obesity by suppressing inflammatory actions of macrophages and release
      of monocyte chemoattractant protein-1 from adipocytes.
AB  - Inflammation plays a key role in obesity-related pathologies such as
      cardiovascular disease, type II diabetes, and several types of cancer. Obesity
      induced inflammation entails the enhancement of the recruitment of macrophages
      into adipose tissue and the release of various proinflammatory proteins from fat
      tissue. Therefore, the modulation of inflammatory responses in obesity may be
      useful for preventing or ameliorating obesity-related pathologies. Some spice
      derived components, which are naturally occurring phytochemicals, elicit
      antiobesity and antiinflammatory properties. In this study, we investigated
      whether active spice-derived components can be applied to the suppression of
      obesity-induced inflammatory responses. Mesenteric adipose tissue was isolated
      from obese mice fed a high-fat diet and cultured to prepare an adipose tissue
      conditioned medium. Raw 264.7 macrophages were treated with the adipose tissue
      conditioned medium with or without active spice-derived components (i.e., diallyl
      disulfide, allyl isothiocyanate, piperine, zingerone and curcumin). Chemotaxis
      assay was performed to measure the degree of macrophage migration. Macrophage
      activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha),
      nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The
      active spice-derived components markedly suppressed the migration of macrophages
      induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent
      manner. Among the active spice-derived components studied, allyl isothiocyanate,
      zingerone, and curcumin significantly inhibited the cellular production of
      proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly
      inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that
      the spice-derived components can suppress obesity-induced inflammatory responses
      by suppressing adipose tissue macrophage accumulation or activation and
      inhibiting MCP-1 release from adipocytes. These spice-derived components may have
      a potential to improve chronic inflammatory conditions in obesity.

PMID- 17196623
TI  - Inhibition of angiogenic differentiation of human umbilical vein endothelial
      cells by diallyl disulfide (DADS).
AB  - Angiogenesis is a crucial step in the growth and metastasis of cancers. The
      activation of endothelial cells and their further behaviour are very critical
      during angiogenesis. We analyzed the effect of diallyl disulfide (DADS) on
      angiogenesis in in vitro models using human umbilical vein endothelial cells
      (HUVECs). DADS significantly inhibited endothelial cell migration, invasion and
      tube formation. (3)H-thymidine proliferation assay clearly showed the inhibitory
      effect of DADS on the proliferation of HUVECs in vitro. The role of
      metalloproteinases has been shown to be important in angiogenesis; therefore,
      zymography was performed to determine whether DADS affected protease activity.
      Gelatin zymographic analysis showed the inhibitory effect of DADS on the
      activation of matrix metalloproteinases-MMP-2 and MMP-9. These findings suggest
      that DADS acts as an angiogenesis inhibitor by inhibiting the activation of
      matrix metalloproteinases during endothelial morphogenesis.

PMID- 17196624
TI  - Cortisol levels and anxiety-related behaviors in cattle.
AB  - This investigation was conducted to examine the relationship between cortisol
      levels and anxiety-related behavior in nine Angus/Hereford cows. In a non
      stressful pasture setting, measures were taken of rumination, distance from
      another cow, and body position. In a stressful holding pen situation, measures
      were taken of vocalizations and resistance to entering a squeeze chute. Cortisol
      was measured in serum samples. Subjects with high levels of cortisol spent less
      time ruminating (p=0.007) and vocalized more (p=0.07) than subjects with low
      levels of cortisol. Regardless of statistical significance, all mean differences
      were in the predicted direction. Cortisol levels were correlated with time spent
      ruminating (p=0.004) and later entrance to the squeeze chute (p=0.10). All
      correlations were also in the predicted direction. These findings provide
      consistent support for the link between cortisol and anxiety-related behavior in
      beef cattle, and the findings have theoretical and practical implications.

PMID- 17196625
TI  - Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR
      and/or LC/MS.
AB  - The newly established hyphenated instrumentation of LC/DAD/SPE/NMR and
      LC/UV/(ESI)MS techniques have been applied for separation and structure
      verification of the major known constituents present in Greek Hypericum
      perforatum extracts. The chromatographic separation was performed on a C18
      column. Acetonitrile-water was used as a mobile phase. For the on-line NMR
      detection, the analytes eluted from column were trapped one by one onto separate
      SPE cartridges, and hereafter transported into the NMR flow-cell. LC/DAD/SPE/NMR
      and LC/UV/MS allowed the characterization of constituents of Greek H. perforatum,
      mainly naphtodianthrones (hypericin, pseudohypericin, protohypericin,
      protopseudohypericin), phloroglucinols (hyperforin, adhyperforin), flavonoids
      (quercetin, quercitrin, isoquercitrin, hyperoside, astilbin, miquelianin, I3,II8
      biapigenin) and phenolic acids (chlorogenic acid, 3-O-coumaroylquinic acid). Two
      phloroglucinols (hyperfirin and adhyperfirin) were detected for the first time,
      which have been previously reported to be precursors in the biosynthesis of
      hyperforin and adhyperforin.

PMID- 17196626
TI  - Sesquiterpene coumarins from Ferula szowitsiana and in vitro antileishmanial
      activity of 7-prenyloxycoumarins against promastigotes.
AB  - Two new sesquiterpene coumarins, named szowitsiacoumarin A (1) and
      szowitsiacoumarin B (2), and a phenylpropanoid derivative, 2-epihelmanticine (3),
      together with nine known compounds, auraptene (4), umbelliprenin (5), galbanic
      acid (6), methyl galbanate (7), farnesiferol B (8), farnesiferol C (9),
      persicasulfide A (10), beta-sitosterol and stigmasterol were isolated from the
      roots of Ferula szowitsiana. The structures of these compounds were elucidated by
      extensive spectroscopic methods including 1D-((1)H and (13)C) and 2D-NMR
      experiments (DQF-COSY, HSQC, HMBC, and ROESY) as well as HR-MALDI-MS analysis.
      Since the configuration of 2-epihelmanticine was previously only partly
      determined, a relative configurational analysis of its four stereocenters was
      carried out on the basis of the recently reported J-based method. The inhibiting
      activity of prenylated coumarins, auraptene (4) and umbelliprenin (5), in
      addition to galbanic acid (6), as major component, and of the Me(2)CO extract of
      Ferula szowitsiana (Apiaceae) roots has been evaluated against promastigotes of
      Leishmania major. Umbelliprenin and auraptene showed significant activity with
      IC(50) values of 4.9microg/ml (13.3microM) and 5.1microg/ml (17.1microM) after
      48h incubation, respectively.

PMID- 17196627
TI  - ent-Beyerane diterpenoids from the heartwood of Excoecaria parvifolia.
AB  - Chromatographic fractionations of the toluene extract of the heartwood of
      Excoecaria parvifolia collected in Australia resulted in the isolation of 12
      beyerane diterpenes (1-12), and the triterpene, lupeol. Four of the isolated
      diterpenoids (5-7 and 12) have unusual structures: ent-3-oxa-beyer-15-en-2-one,
      (5); ent-15,16-epoxy-2-hydroxy-19-norbeyer-1,4-dien-3-one (6); methyl ent-2,4
      seco-15,16-epoxy-4-oxo-3,19-dinorbeyer-15-en-2-oate (7); and ent-2,17-dihydroxy
      19-norbeyer-1,4,15-trien-3-one (12). The structures were established by
      spectroscopic analyses, NMR data comparisons with similar diterpenes, and
      chemical correlations. All the diterpenes are assumed to have the same absolute
      configuration as the co-occurring (+)-stachenol (4). Diosphenol 2 and nor-lactone
      5 exhibited significant potency in bioassays for cytotoxic activity against
      leukemia cells (L1210). Plausible biosynthetic pathways are proposed to explain
      the origin of the diterpene metabolites.

PMID- 17196628
TI  - Lung toxicity of nitrogen mustard may be mediated by nitric oxide and
      peroxynitrite in rats.
AB  - Nitric oxide (NO) has previously been shown to be responsible for nitrogen
      mustard (NM)-induced tissue toxicity. Excessive amounts of NO are known to be
      able to produce peroxynitrite, an important reactive nitrogen compound, by
      reacting with superoxide. Previous studies reported that NO synthase inhibitors
      are able to prevent NM toxicity. The aim of this study was to evaluate whether
      peroxynitrite is also responsible for NM-induced lung tissue damage in rats.
      Wistar rats were divided into four groups. NM was injected intratracheally and
      was treated with the selective inducible nitric oxide synthase (iNOS) inhibitor
      aminoguanidine (AG) (intraperitoneal) or the peroxynitrite scavenger ebselen
      (intragastric). Control animals were exposed to saline only. NM injection caused
      both oxidative and nitrosative stress, reflected by dramatically increased levels
      of the lipid peroxidation end product malondialdehyde (MDA), iNOS activation and
      urine nitrite-nitrate (NOx) values. Histopathological evaluation demonstrated
      lung damage with NM exposure. AG blocked iNOS activation and decreased urine NOx
      levels, and resulted in less histopathological changes in the lung. Although the
      histopathological outcome was found to be similar to AG, ebselen did not change
      urinary NOx or lung iNOS levels. Furthermore, ebselen was more able than AG to
      protect against MDA accumulation. In conclusion, the ability of ebselen to
      prevent against lung damage without blocking NO synthesis suggests that
      peroxynitrites may have an important role in the pathogenesis of NM toxicity in
      addition to NO.

PMID- 17196629
TI  - Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is
      associated with reactive oxygen species production and mitochondrial membrane
      depolarization.
AB  - Sanguinarine is a benzopheanthridine alkaloid present in the root of Sanguinaria
      canadensis L. and Chellidonium majus L. In this study, sanguinarine (2 and 3
      microM) exhibited cytotoxicity to KB cancer cells by decreasing MTT reduction to
      83% and 52% of control after 24-h of exposure. Sanguinarine also inhibited the
      colony forming capacity (>52-58%) and growth of KB cancer cells at concentrations
      higher than 0.5-1 microM. Short-term exposure to sanguinarine (>0.5 microM)
      effectively suppressed the adhesion of KB cells to collagen and fibronectin (FN).
      Sanguinarine (2 and 3 microM) induced evident apoptosis as indicated by an
      increase in sub-G0/G1 populations, which was detected after 6-h of exposure. Only
      a slight increase in cells arresting in S-phase and G2/M was noted. Induction of
      KB cell apoptosis and necrosis by sanguinarine (2 and 3 microM) was further
      confirmed by Annexin V-PI dual staining flow cytometry and the presence of DNA
      fragmentation. The cytotoxicity by sanguinarine was accompanied by an increase in
      production of reactive oxygen species (ROS) and depolarization of mitochondrial
      membrane potential as indicated by single cell flow cytometric analysis of DCF
      and rhodamine fluorescence. NAC (1 and 3 mM) and catalase (2000 U/ml) prevented
      the sanguinarine-induced ROS production and cytotoxicity, whereas
      dimethylthiourea (DMT) showed no marked preventive effect. These results suggest
      that sanguinarine has anticarcinogenic properties with induction of ROS
      production and mitochondrial membrane depolarization, which mediate cancer cell
      death.

PMID- 17196630
TI  - Delivery methods for peptide and protein toxins in insect control.
AB  - Since the introduction of DDT in the 1940s, arthropod pest control has relied
      heavily upon chemical insecticides. However, the development of insect
      resistance, an increased awareness of the real and perceived environmental and
      health impacts of these chemicals, and the need for systems with a smaller
      environmental footprint has stimulated the search for new insecticidal compounds,
      novel molecular targets, and alternative control methods. In recent decades a
      variety of biocontrol methods employing peptidic or proteinaceous insect-specific
      toxins derived from microbes, plants and animals have been examined in the
      laboratory and field with varying results. Among the many interdependent factors
      involved with the production of a cost-effective pesticide--production expense,
      kill efficiency, environmental persistence, pest-specificity, pest resistance
      development, public perception and ease of delivery--sprayable biopesticides have
      not yet found equal competitive footing with chemical counterparts. However,
      while protein/peptide-based biopesticides continue to have limitations, advances
      in the technology, particularly of genetically modified organisms as
      biopesticidal delivery systems, has continually progressed. This review
      highlights the varieties of delivery methods currently practiced, examining the
      strengths and weaknesses of each method.

PMID- 17196631
TI  - Neutralization of the haemorrhagic activities of viperine snake venoms and venom
      metalloproteinases using synthetic peptide inhibitors and chelators.
AB  - Envenoming by the West African saw-scaled viper, Echis ocellatus resembles that
      of most vipers, in that it results in local blistering, necrosis and sometimes
      life-threatening systemic haemorrhage. While effective against systemic
      envenoming, current antivenoms have little or no effect against local tissue
      damage. The major mediators of local venom pathology are the zinc-dependant snake
      venom metalloproteinases (SVMPs). The high degree of structural and functional
      homology between SVMPs and their mammalian relatives the matrix
      metalloproteinases (MMPs) suggests that substrate/inhibitor interactions between
      these subfamilies are likely to be analogous. In this study, four recently
      developed MMP inhibitors (MMPIs) (Marimastat, AG-3340, CGS-270 23A and Bay-12
      9566) are evaluated in addition to three metal ion chelators (EDTA, TPEN and
      BAPTA) for their ability to inhibit the haemorrhagic activities of the medically
      important E. ocellatus venom and one of its haemorrhagic SVMPs, EoVMP2. As
      expected, the metal ion chelators significantly inhibited the haemorrhagic
      activities of both whole E. ocellatus venom and EoVMP2, while the synthetic MMPIs
      show more variation in their efficacies. These variations suggest that individual
      MMPIs show specificity towards SVMPs and that their application to the
      neutralization of local haemorrhage may require a synthetic MMPI mixture,
      ensuring that a close structural component for each SVMP is represented.

PMID- 17196633
TI  - Mitigation of age-dependent oxidative damage to DNA in rat heart by carnitine and
      lipoic acid.
AB  - Endogenous damage to mtDNA by free radicals is believed to be a major
      contributory factor to aging. Mitochondrial DNA exists in a highly genotoxic
      environment created by exposure to reactive oxygen species and thus are more
      vulnerable to free radical attack. In the present study we have focused on the
      age associated alterations to DNA during aging and in parallel investigated the
      efficacy of carnitine (300 mg/kg bw) and lipoic acid (100 mg/kg bw) for 28 days
      in altering these changes. We observed a decline in the content of both
      mitochondrial and nuclear DNA during aging with an exponential increase in the 8
      OHdG levels. We also observed an age-dependent increase in DNA protein crosslinks
      and double strand and single strand breaks. Supplementation of carnitine and
      lipoic acid during aging process decreased the incidence of these DNA damage,
      therefore suggesting that this feeding regimen inhibits the accumulation of age
      associated oxidative DNA damage.

PMID- 17196632
TI  - Suppression of NF-kappaB and AP-1 activation in monocytic cells persistently
      infected with measles virus.
AB  - A major cause of the high morbidity and mortality associated with measles
      infection is attributed to virus-mediated immunosuppression. In this report, we
      present evidence for a novel strategy of immunosuppression by the measles virus.
      We observed a marked suppression of lipopolysaccharide (LPS)-induced IL-8,
      RANTES, TNF-alpha and IL-6 production and NF-kappaB activation in human monocytic
      cell lines persistently infected with measles virus. This effect was not observed
      in human epithelial cells lines persistently infected with measles virus. There
      were no significant differences in expression levels of Toll-like receptors
      (TLRs) and their associated molecules, or other intracellular signaling molecules
      of the NF-kappaB signaling pathway in measles-virus-infected monocytic cells
      compared to uninfected cells. Infected monocytic cells exhibited decreased LPS
      induced DNA binding of NF-kappaB and phosphorylation of JNK, namely activation of
      transcription factors NF-kappaB and AP-1. NF-kappaB was constitutively activated
      in human epithelial cells persistently infected with measles virus, and LPS
      treatment resulted in further activation. The cell-type-specific suppression of
      NF-kappaB activation represents a potential strategy of escape from the host
      immune system by measles virus via induced immunological silencing in infected
      cells.

PMID- 17196634
TI  - Identifying model pollutants to investigate biodegradation of hazardous XOCs in
      WWTPs.
AB  - Xenobiotic organic compounds (XOCs) in wastewater treatment plant (WWTP)
      effluents might cause toxic effects in ecosystems. Several investigations have
      emphasized biodegradation as an important removal mechanism to reduce pollution
      with XOCs from WWTP effluents. The aim of the study was to design a screening
      tool to identify and select hazardous model pollutants for the further
      investigation of biodegradation in WWTPs. The screening tool consists of three
      criteria: The XOC is present in WWTP effluents, the XOC constitutes an
      intolerable risk in drinking water or the environment, and the XOC is expected to
      be biodegradable in WWTPs. The screening tool was tested on bisphenol A (BPA),
      carbamazepine (CBZ), di(2ethylhexyl)-phthalate (DEHP), 17beta-estradiol (E2),
      estrone (E1), 17alpha-ethinyloetradiol (EE2), ibuprofen, naproxen, nonylphenol
      (NP), and octylphenol (OP). BPA, DEHP, E2, E1, EE2, and NP passed all criteria in
      the screening tool and were selected as model pollutants. OP did not pass the
      filter and was rejected as model pollutant. CBZ, ibuprofen, and naproxen were not
      finally evaluated due to insufficient data.

PMID- 17196635
TI  - Long-term behavioral and developmental consequences of pre- and perinatal
      nicotine.
AB  - Research has shown that cigarette use during pregnancy can result in increased
      fetal mortality, sudden infant death syndrome, and behavioral and attentional
      disorders during childhood. Neurochemical and behavioral consequences of prenatal
      nicotine exposure have been well documented although few studies have examined
      long-term behavioral consequences that persist into adulthood. In this study,
      fifty-eight male and female Long-Evans rats were exposed to chronic nicotine
      prenatally and postnatally via subcutaneous infusions (0.96 mg/kg/day) in the
      dam. Nicotine exposure continued in the pups via maternal milk until the dams'
      osmotic mini-pumps became exhausted at approximately postnatal day (P) 11. At
      weaning, animals were group housed until behavioral testing at P60 to assess
      spatial learning and memory in the Morris water maze (MWM). Mild deficits in
      spatial learning were observed in nicotine-exposed females. These behavioral
      differences were accompanied by significant reduction in weight gain of nicotine
      exposed females beginning at puberty, suggesting a hormonal interaction. Long
      term effects of nicotine exposure were less striking in males. Nicotine-exposed
      males had significantly slower swim speeds than controls, but latency to reach
      the hidden platform was equal between groups by the conclusion of testing. Weight
      gain in males did not differ between groups as a result of prenatal nicotine
      exposure.

PMID- 17196636
TI  - Cholecystokinin is necessary for the expression of morphine conditioned place
      preference.
AB  - There is evidence that the neuropeptide cholecystokinin (CCK) is important for
      the rewarding effects of drugs of abuse. However, less is known regarding the
      role of CCK in drug seeking and craving. The present study investigated whether
      the CCK(B) antagonist L-365, 260 could block morphine-induced drug seeking using
      the conditioned place preference paradigm and whether the dopaminergic reward
      pathway contributes to the effect of L-365, 260 on expression of morphine place
      preference. We found that systemic administration of the CCK(B) antagonist L-365,
      260 attenuates the expression of morphine-induced drug seeking as assessed using
      conditioned place preference (CPP) and shows that this effect is mediated by
      CCK(B) receptors in the anterior nucleus accumbens (NAcc). Additionally, we
      demonstrate that this effect is dependent on D(2) receptor activation in the
      anterior nucleus accumbens (NAcc). These results indicate that endogenous CCK
      modulates the incentive-salience of morphine-associated cues and suggest that CCK
      antagonists may be useful in the treatment of drug craving.

PMID- 17196637
TI  - Morphine analgesic tolerance in 129P3/J and 129S6/SvEv mice.
AB  - Morphine analgesic tolerance is heritable in both humans and rodents, with some
      individuals and strains exhibiting little and others exhibiting robust tolerance.
      129S6/SvEv and 129P3/J mice reportedly do not demonstrate tolerance to morphine
      analgesia. Using our laboratory's standard morphine tolerance regimen and a
      between-subjects design, tolerance developed in the hot plate and tail withdrawal
      assays as indicated by a change in analgesic efficacy following a morphine
      challenge dose. Furthermore, the non-competitive NMDA receptor antagonist MK-801
      (dizocilipine) blocked morphine tolerance in 129S6/SvEv and CD-1 mice in the hot
      plate assay. As previously reported, when a within-subjects design and cumulative
      dosing was employed, no tolerance was observed in the 129P3/J strain. However,
      using the same morphine regimen and a between-subjects design, comparable
      tolerance developed between 129P3/J and C57BL/6J strains following a single
      challenge dose of morphine. Spontaneous hyperalgesia was observed in the tail
      withdrawal assay following chronic morphine in C57BL/6J, but not 129P3/J mice.
      Additionally, morphine-tolerant C57BL/6J mice, but not 129P3/J mice, exhibited a
      large increase in the frequency of tail flicks during the first second following
      the baseline nociceptive response which may facilitate detection of the response
      during the tolerant state. We conclude that the method of tolerance assessment
      affects the ability to detect tolerance and thus may affect the degree and
      pattern of heritability of this trait and this could have implications for gene
      mapping studies.

PMID- 17196638
TI  - Evaluation of muscarinic and nicotinic receptor antagonists on attention and
      working memory.
AB  - Cholinergic receptor antagonists are commonly used to model attentional and
      mnemonic impairments associated with neuropsychiatric disorders such as
      Alzheimer's disease. However, few studies have systematically assessed the
      effects of these drugs following manipulations that affect attention or working
      memory within the same task. In the present experiment, rats were trained to
      discriminate visual signals from "blank" trials when no signal was presented.
      This task was modified to include retention intervals on some trials to tax
      working memory. During standard task performance, rats received systemic
      injections of the muscarinic receptor antagonist, scopolamine, or of the
      nicotinic receptor antagonist, mecamylamine. A second experiment tested the
      effects on this task of co-administering doses of scopolamine and mecamylamine
      that, when administered alone, did not significantly affect task performance.
      Scopolamine (0.3 and 1.0 mg/kg) decreased detection of 500 ms signals but did not
      affect accurate identification of non-signals. Scopolamine did not differentially
      affect performance across the retention interval. Elevated omission rates were
      associated with high doses of scopolamine or mecamylamine. Combination drug
      treatment was associated with decreased signal detection and elevated omission
      rates. Collectively, the data suggest that muscarinic and nicotinic receptor
      antagonists do not exclusively impair working memory.

PMID- 17196639
TI  - Effect of acute and repeated treatment with mirtazapine on the immunity of
      noradrenaline transporter knockout C57BL/6J mice.
AB  - Pathological immunoactivation is thought to play an important role in the
      etiology of depression; however, the effect of novel antidepressant drugs on
      immunity has been poorly recognized. Mirtazapine, an antidepressant drug,
      enhances noradrenergic and serotonergic neurotransmissions, which are crucially
      involved in the regulation of immune system activity. In the present study we
      examined the effect of acute and seven-day repeated administration of mirtazapine
      (20 mg/kg, i.p.) on immunoreactivity in noradrenaline transporter knockout (NET
      KO) and wild-type male C57BL/6J mice subjected to the forced swimming test (FST).
      Mirtazapine decreased immobility time in the FST after acute, but not seven-day
      repeated, administration to C57BL/6J mice. Lack of the antidepressant effect of
      mirtazapine was observed, after acute and repeated administration to NET-KO mice,
      although those mice showed a significantly shorter immobility time in the FST
      than did wild-type animals. Seven-day repeated mirtazapine administration to wild
      type mice suppressed the proliferative activity of splenocytes and their ability
      to produce pro-inflammatory cytokines, whereas production of IL-4 was stimulated.
      Acute mirtazapine administration did not change immune parameters in C57BL/6J
      mice. In NET-KO mice, acute and seven-day repeated mirtazapine administration
      reduced the proliferative activity of splenocytes and their ability to produce
      pro-inflammatory cytokines. This study indicates that, in comparison with wild
      type C57BL/6J mice, NET-KO mice show enhanced mobility, which is not further
      potentiated by mirtazapine treatment. Furthermore, the NET-KO mice display higher
      susceptibility to the immunosuppressive effects of mirtazapine than do the wild
      type animals. The present paper postulates an essential role of noradrenergic
      system in the immunological and behavioral effects of mirtazapine.

PMID- 17196640
TI  - Effects of acute and chronic ethanol exposure on the behavior of adult zebrafish
      (Danio rerio).
AB  - The zebrafish has been a popular subject of embryology and genetic research for
      the past three decades. Recently, however, the interest in its neurobiology and
      behavior has also increased. Nevertheless, compared to other model organisms,
      e.g., rodents, zebrafish behavior is understudied and very few behavioral
      paradigms exist for mutation or drug screening purposes. Alcoholism is one of the
      biggest and costliest diseases whose mechanisms are not well understood. Model
      organisms such as the zebrafish may be utilized in this line of research.
      Previously, we investigated the effects of acute ethanol exposure on adult
      zebrafish using four behavioral paradigms and employing manual quantification
      methods. Here, we study the effects of chronic ethanol exposure and analyze how
      it modifies the effects of acute ethanol treatment. We employ a videotracking
      based automated quantification method in a predator model paradigm and show that
      this method is capable of detecting an avoidance reaction that is ameliorated by
      higher doses of ethanol, a potential anxiolytic effect. Importantly, we also
      demonstrate that chronic, two week long, exposure to ethanol results in
      significant adaptation to this substance in adult zebrafish. Overall, our results
      suggest that zebrafish will be an appropriate subject for high throughput
      screening applications aimed at the analysis of the mechanisms and pharmacology
      of acute and chronic ethanol induced changes in the vertebrate brain.

PMID- 17196641
TI  - TNF-alpha (-308 G/A) and CD14 (-159T/C) polymorphisms in the bronchial
      responsiveness of Korean children with asthma.
AB  - BACKGROUND: TNF-alpha is a pivotal proinflammatory cytokine increased in
      asthmatic airways. The TNF-alpha gene family might be linked to asthma or
      bronchial hyperresponsiveness (BHR), and TNF-alpha production might be modulated
      by CD14(+) cells. OBJECTIVE: We investigated the association between asthma
      susceptibility or asthma-related phenotypes and TNF-alpha (-308G/A) polymorphism
      and examined the combined effect with CD14 (-159T/C) polymorphism in Korean
      children. METHODS: Asthmatic (n = 788) and control (n = 153) children were
      evaluated for asthma phenotypes. Genotypes were determined by using the single
      base extension method and PCR-restriction fragment length polymorphism. RESULTS:
      There was no difference between asthmatic children and control subjects in terms
      of the allele frequencies of TNF-alpha (-308G/A) and CD14 (-159T/C).
      Significantly lower PC(20) values were seen in asthmatic (P = .016) children with
      the TNF-alpha risk allele (-308A). Higher frequencies of 1 or 2 copies of the
      risk allele were found in asthmatic children with moderate-to-severe BHR to
      methacholine and exercise compared with control children (adjusted odds ratio of
      2.57 [95% CI, 1.30-5.08] and adjusted odds ratio of 2.04 [95% CI 0.99-4.20],
      respectively). In addition, asthmatic children with risk alleles at both loci had
      significantly greater BHR than those homozygous for the common alleles (P =
      .018). CONCLUSION: The TNF-alpha promoter polymorphism (-308G/A) might be
      associated with severe BHR in Korean children with asthma. In addition, these
      children show a synergistic effect between the TNF-alpha promoter (-308A) and
      CD14 promoter (-159C) polymorphisms in terms of BHR. CLINICAL IMPLICATIONS: The
      TNF-alpha polymorphism might be a disease-modifying gene in asthma and modulated
      by the CD14 gene.

PMID- 17196643
TI  - Effects of 50 Hz extremely low frequency magnetic field on the morphology and
      function of boar spermatozoa capacitated in vitro.
AB  - The aim of this study was to evaluate the effect of an acute exposure to a
      sinusoidal MF-ELF (50 Hz, 1mT) on the ability of boar mature spermatozoa to
      acquire the fertilizing competence in vitro. The spermatozoa exposed during the
      4h of incubation to the MF-ELF were evaluated for morphological (surface
      morphology and acrosome integrity) and functional parameters (cell viability,
      motility, induction of acrosomal reaction, AR, and the ability to in vitro
      fertilize oocytes). In parallel, the intracellular Ca(2+) levels as well as the
      major mechanisms of Ca(2+) clearance were assessed: (45)Ca intakes and
      intracellular Ca(2+) sequestration by analyzing intracellular Ca(2+) elevation
      induced by thapsigargin or studying mitochondrial function with Mito-Tracker. The
      MF-ELF exposure did not affect sperm viability and morphology during the first h
      of incubation when sperm Ca(2+) homeostasis were already compromised. First of
      all, MF-ELF treated spermatozoa showed resting intracellular Ca(2+) levels
      significantly lower than those recorded in controls. This result was dependent on
      a lower extracellular Ca(2+) intake and from the inhibitory role exerted on both
      intracellular Ca(2+) storages. As a consequence, after 1h of incubation MF-ELF
      exposed cells displayed a reduced motility, a modest reactivity when coincubated
      with solubilized zonae pellucidae and a reduction in oocyte penetrating ability.
      After 2 or 4h of incubation, in addition, signs of morphological damage appeared
      on plasma membrane and at acrosomal level. In conclusion, MF-ELF influence
      negatively spermatozoa first by impairing cell Ca(2+) homeostasis then by
      dramatically affecting sperm morphology and function.

PMID- 17196642
TI  - Use of preventive care by the working poor in the United States.
AB  - OBJECTIVE: Examine the association between poverty and preventive care use among
      older working adults. METHOD: Cross-sectional analysis of the pooled 1996, 1998
      and 2000 waves of the Health and Retirement Study, a nationally representative
      sample of older community-dwelling adults, studying self-reported use of
      cervical, breast, and prostate cancer screening, as well as serum cholesterol
      screening and influenza vaccination. Adults with incomes within 200% of the
      federal poverty level were defined as poor. RESULTS: Among 10,088 older working
      adults, overall preventive care use ranged from 38% (influenza vaccination) to
      76% (breast cancer screening). In unadjusted analyses, the working poor were
      significantly less likely to receive preventive care. After adjustment for
      insurance coverage, education, and other socio-demographic characteristics, the
      working poor remained significantly less likely to receive breast cancer (RR
      0.92, 95% CI, 0.86-0.96), prostate cancer (RR 0.89, 95% CI, 0.81-0.97), and
      cholesterol screening (RR 0.91, 95% CI, 0.86-0.96) than the working non-poor, but
      were not significantly less likely to receive cervical cancer screening (RR 0.96,
      95% CI, 0.90-1.01) or influenza vaccination (RR 0.92, 95% CI, 0.84-1.01).
      CONCLUSION: The older working poor are at modestly increased risk for not
      receiving preventive care.

PMID- 17196645
TI  - Fluorescent emission of varied shades of resin composites.
AB  - OBJECTIVES: The objectives of this study were to measure the fluorescent emission
      and the corresponding color difference by the inclusion and exclusion of the UV
      component of the standard illuminant D65 of varied shades of commercial resin
      composites, and to determine the influence of the color parameters and difference
      in color parameters by the UV component on the color difference caused by the
      fluorescent emission. METHOD: Eight light-curing resin composites, a total of 41
      shades, were studied. Color and spectral reflectance of specimens, 12 mm in
      diameter and 1mm in thickness, were measured on a reflection spectrophotometer.
      An UV filter was adjusted to 100% or 0% location to include or exclude the UV
      component of the standard illuminant D65. From the spectral reflectance values,
      subtraction spectrum by the inclusion or exclusion of the UV component was
      calculated, and fluorescence peak height was determined. Color difference caused
      by the inclusion or exclusion of the UV component (DeltaE*(ab)-FL) was
      calculated. Differences in color coordinates (DeltaL*, Deltaa* and Deltab*) by
      the inclusion or the exclusion of the UV component were calculated. RESULTS:
      Fluorescence peak height and DeltaE*(ab)-FL were influenced by the brand and the
      shade of resin composites and there was a significant interaction between the
      variables based on two-way ANOVA (p<0.05). DeltaE*(ab)-FL was correlated with the
      chroma component of the shade, and also with Deltab* [standardized partial
      correlation coefficient (beta)=-0.699], DeltaL* (beta=0.464) and Deltaa*
      (beta=0.105) based on multiple regression analyses (p<0.05). CONCLUSION:
      Fluorescent emission was influenced by the brand and the shade of resin
      composites. Fluorescent resin composites showed color shift to blue direction and
      increased lightness under the UV included illumination.

PMID- 17196644
TI  - The relationship between reduplicated babble onset and laterality biases in
      infant rhythmic arm movements.
AB  - This study examined changes in rhythmic arm shaking and laterality biases in
      infants observed longitudinally at three points: just prior to, at, and just
      following reduplicated babble onset. Infants (ranging in age from 4 to 9 months
      at babble onset) were videotaped at home as they played with two visually
      identical audible and silent rattles presented at midline for 1.5 min each. Rate
      of rattle shaking increased sharply from the pre-babble to the babble onset
      session; but there was no indication that this increase was specific to the right
      arm. This finding suggests that the link between babble onset and increased
      rhythmic arm activity may not be the product of language-specific mechanisms, but
      is rather part of a broader developmental process that is also perceptual and
      motor.

PMID- 17196646
TI  - Carbon isotopes and iodine concentrations in a Mississippi River delta core
      recording land use, sediment transport, and dam building in the river's drainage
      basin.
AB  - Sedimentary material from coastal and nearshore areas in the Mississippi Delta
      region are comprised of different organic carbon sources with diverse ages that
      require isotopic and elemental records for resolving the various sources of plant
      residues. Carbon isotopic ((13)C, (14)C) values were used to differentiate
      contributions from plants using the C3, C4, and/or CAM (crassulacean acid
      metabolism) carbon fixation pathways., and iodine concentrations indicated that
      wetland plant residues are a significant source of organic carbon in a sediment
      core from the Mississippi River delta region collected at a 60 m water depth.
      This sediment core had been extensively described in Oktay et al. [Oktay, S.D.,
      Santschi, P.H., Moran, J.E., Sharma, P., 2000. The (129)Iodine Bomb Pulse
      Recorded in Mississippi River delta Sediments: Results from Isotopes of I, Pu,
      Cs, Pb, and C. Geochim. Cosmochim. Acta 64 (6), 989-996.] and significantly,
      includes unique features that had not previously been seen in the marine
      environment. These special features include a plutonium isotopic close-in fallout
      record that indicates a purely terrestrial source for these sediment particles
      and the elements associated with it, and a distinct iodine isotopic peak (as well
      as peaks for plutonium and cesium isotopes) that indicate little bioturbation in
      this core. Our carbon isotopic and iodine data can thus be compared to published
      records of changes in drainage basin land use, river hydrology, and hydrodynamic
      sorting of suspended particles to elucidate if these changes are reflected in
      nearshore sediments. This comparison suggests a significant contribution for
      organic carbon (OC) from C4 plants to these sediments during the 1950's to early
      1960's. Relative older carbon isotopes, and episodically high iodine
      concentrations (up to 34 ppm) were observed during this time period that (1)
      indicate sediment deposition that is coincident with the times of major
      hydrological changes induced from dam and levee building in both the upper and
      lower reaches of the Mississippi River drainage basin, and (2) suggest episodic
      organic carbon deposition from wetland plant residues.

PMID- 17196647
TI  - Identification and characterization of a novel (S)-ketoprofen-specific esterase.
AB  - A new (S)-ketoprofen specific esterase (EST-Y29) was identified from a metagenome
      library from environmental samples, which showed homologies with class C-beta
      lactamase, penicillin binding protein, and other lipases/esterases. In order to
      investigate the biochemical and biophysical properties, the recombinant protein
      was overexpressed, purified to homogeneity, and characterized. This EST-Y29 has
      high catalytic activity against p-nitrophenyl esters of short fatty acids (C(2)
      and C(4)) and alpha-naphthyl acetate with activation energy of 30.4 kJ/mol. We
      have further characterized EST-Y29 using high performance liquid chromatography
      (HPLC), circular dichroism (CD), dynamic light scattering (DLS) and size
      exclusion chromatography (SEC).

PMID- 17196648
TI  - In vitro and in vivo characteristics of PCL scaffolds with pore size gradient
      fabricated by a centrifugation method.
AB  - Polycaprolactone (PCL) cylindrical scaffolds with gradually increasing pore size
      along the longitudinal direction were fabricated by a novel centrifugation method
      to investigate pore size effect on cell and tissue interactions. The scaffold was
      fabricated by the centrifugation of a cylindrical mold containing fibril-like PCL
      and the following fibril bonding by heat treatment. The scaffold showed gradually
      increasing pore size (from approximately 88 to approximately 405 microm) and
      porosity (from approximately 80% to approximately 94%) along the cylindrical axis
      by applying the centrifugal speed, 3000 rpm. The scaffold sections were examined
      for their in vitro cell interactions using different kinds of cells
      (chondrocytes, osteoblasts, and fibroblasts) and in vivo tissue interactions
      using a rabbit model (skull bone defects) in terms of scaffold pore sizes. It was
      observed that different kinds of cells and bone tissue were shown to have
      different pore size ranges in the scaffold for effective cell growth and tissue
      regeneration. The scaffold section with 380-405 microm pore size showed better
      cell growth for chondrocytes and osteoblasts, while the scaffold section with 186
      200 microm pore size was better for fibroblasts growth. Also the scaffold section
      with 290-310 microm pore size showed faster new bone formation than those of
      other pore sizes. The pore size gradient scaffolds fabricated by the
      centrifugation method can be a good tool for the systematic studies of the
      interactions between cells or tissues and scaffolds with different pore size.

PMID- 17196650
TI  - Arginine-conjugated polypropylenimine dendrimer as a non-toxic and efficient gene
      delivery carrier.
AB  - We synthesized arginine-conjugated polypropylenimine dendrimer G2 (DAB-8), PPI2-R
      for gene delivery systems. Synthesized PPI2-R could retard plasmid DNA at a
      weight ratio of 4 completely and PPI2-R polyplexes showed a fluorescence of less
      than 10% over a charge ratio of 2 by PicoGreen reagent assay, suggesting its good
      DNA condensing ability. The size of PPI2-R polyplex was measured to about 200nm
      at a charge ratio of 150. PPI2-R displayed 80-90% cell viability at even a
      150microg/mL concentration. Transfection efficiency of PPI2-R was found to be
      high comparable to that of PEI25kD and to be 8-214 times higher than that of
      unmodified PPI2 on HeLa and 293 cells. Moreover, PPI2-R showed 4 times higher
      transfection efficiency than PEI25kD, treating with 10microg pDNA because of its
      low cytotoxicity on HeLa cells. Finally, PPI2-R showed a transfection efficiency
      2-3 times higher than PEI25kD on HUVECs, showing its potency as a gene delivery
      carrier for primary cells. These results demonstrate that arginine-conjugation of
      PPI2 is successful in developing a low toxic and highly transfection efficient
      gene delivery carrier.

PMID- 17196649
TI  - DLC coatings: effects of physical and chemical properties on biological response.
AB  - Recent trials on diamond-like carbon (DLC) coated medical devices have indicated
      promise for blood interfacing applications. The literature is sparse regarding
      structural and compositional effects of DLC on cellular response. An important
      goal in optimizing blood-interfacing implants is minimal macrophage attachment,
      and maximal albumin:fibrinogen adsorption ratio. DLC coatings deposited by PACVD
      and FAD, were analysed with respect to sp3 content (EELS), hydrogen content
      (ERDA), surface composition (XPS), surface roughness (AFM), surface energy,
      albumin:fibrinogen adsorption ratio, and macrophage viability and attachment. We
      found that increasing surface roughness and surface energy enhanced the
      macrophage viability and the albumin:fibrinogen adsorption ratio. We also found
      that the higher the hydrogen content for a-C:Hs deposited by PACVD, the lower the
      albumin:fibrinogen adsorption ratio, and macrophage attachment. This suggests
      that hydrogen content may be an important factor for influencing the biological
      response of DLC surfaces. Macrophage cells spread well on all DLC surfaces, and
      the surface results indicated the non-toxic nature of the surfaces on the cells
      at the time points tested.

PMID- 17196651
TI  - Crosstalk between L-type calcium channels and ZnT-1, a new player in rate
      dependent cardiac electrical remodeling.
AB  - Crosstalk between two membrane transport systems is an established mechanism
      underlying regulation. In this study, we investigated the interaction between ZnT
      1, a putative plasma membrane zinc transporter, and L-type voltage-dependent
      calcium channels (LTCC). In the atrium of the myocardium decreased activity of
      the LTCC is a dominant feature of patients with atrial fibrillation. The trigger
      for this inhibition has been attributed to the rapid firing rates and consequent
      calcium overload in the atrial cardiomyocytes. However, the underlying mechanism
      of LTCC inhibition is still to be elucidated. Here, we showed that the expression
      of ZnT-1 inhibits the activity of L-type channels during electrical remodeling
      induced by rapid pacing. (i) Direct manipulations of ZnT-1 expression in cultured
      cardiomyocytes either by ZnT-1 overexpression or by ZnT-1 silencing with siRNA,
      decreased or enhanced, respectively, the barium influx through the LTCC. (ii) Co
      expression of ZnT-1 with LTCC in Xenopus oocytes decreased whole cell barium
      current through LTCC. (iii) Rapid pacing of cultured cardiomyocytes (4 h, 100 ms
      cycle) increased ZnT-1 protein expression and inhibited the voltage-dependent
      divalent cation influx through the LTCC. Moreover, silencing ZnT-1 with siRNA
      prevented the rapid pacing induced inhibition of the LTCC (iv) Atrial pacing of
      anesthetized adult rats (4 h, 50 ms cycle) led to a significant increase in
      atrial ZnT-1 protein expression in parallel with the typical decrease of the
      refractory period in the atria. Taken together, these findings demonstrate that
      crosstalk between ZnT-1 and the L-type calcium channels may underlie atrial
      response to rapid pacing, suggesting that ZnT-1 is a significant participant in
      rate-dependent cardiac electrical remodeling.

PMID- 17196652
TI  - On the role of prolyl oligopeptidase in health and disease.
AB  - Prolyl oligopeptidase (POP) is a serine peptidase which digests small peptide
      like hormones, neuroactive peptides, and various cellular factors. Therefore,
      this peptidase has been implicated in many physiological processes as well as in
      some psychiatric disorders, most probably through interference in inositol cycle.
      Intense research has been performed to elucidate, on the one hand, the basic
      structure, ligand binding, and kinetic properties of POP, and on the other, the
      pharmacology of its inhibitors. There is fairly strong evidence of in vivo
      importance of POP on substance P, arginine vasopressin, thyroliberin and
      gonadoliberin metabolism. However, information about the biological relevance of
      POP is not yet conclusive. Evidence regarding the physiological role of POP is
      lacking, which is surprising considering that peptidase inhibitors have been
      exploited for drug development, some of which are currently in clinical trials as
      memory enhancers for the aged and in a variety of neurological disorders. Here we
      review the recent progress on POP research and evaluate the relevance of the
      peptidase in the metabolism of various neuropeptides. The recognition of novel
      forms and relatives of POP may improve our understanding of how this family of
      proteins functions in normal and in neuropathological conditions.

PMID- 17196653
TI  - Characterization and application of a rolling-circle-type plasmid from
      Cupriavidus taiwanensis.
AB  - Two small cryptic plasmids, pTJ86-1 and pTJ86-2, identified in Cupriavidus
      taiwanensis strain TJ86, were detected and characterized. Complete sequencing of
      pTJ86-1 and pTJ86-2 revealed these plasmids to be 2221 and 2229bp in length with
      a GC content of 61.7% and 61.6%, respectively. Both plasmids harbored four open
      reading frames (ORF1, 2, 3 and 4). Only the predicted ORF1 gene product of both
      plasmids (436 amino acids) was homologous to Rep proteins previously identified
      on plasmids replicated using a rolling-circle replication (RCR). A double
      stranded origin (DSO) of replication, highly conserved in the group III (cluster
      III) RCR plasmids, was identified and located immediately upstream of this
      putative Rep gene. In addition, both plasmids contained a putative single
      stranded origin of replication (SSO) exhibiting similarity to the ssoA-type.
      Detection of single-stranded plasmid DNA by Southern analysis and S1 nuclease
      digestion confirmed that the cryptic plasmid replicated via an RCR mechanism. A
      potential shuttle vector, pS4-tet(R), was constructed by ligation of pTJ86-1 to
      the cloning vector pBluescript II SK(+) along with the insertion of a
      tetracycline-resistance (tet(R)) gene. It was successfully used for the
      transformation of genera Burkholderia and Cupriavidus.

PMID- 17196655
TI  - Genome sequencing analysis of Brazilian chicken anemia virus isolates that lack
      MSB-1 cell culture tropism.
AB  - Specific amino acid (aa) substitutions in VP1, VP2 and VP3 genes were reported as
      a distinctive feature of the American CIA-1 strain, characterized as having a
      variable rate of growth and tropism for different MSB-1 cell sublines [Renshaw
      RW, Soine C, Weinkle T, O'Connell PH, Ohashi K, Watson S, et al. A hypervariable
      region in VP1 of chicken anemia virus mediates rate of spread and cell tropism in
      tissue culture. J Virol 1996;70(12):8872-8]. DNA sequencing of 878 nucleotides
      from twelve Brazilian CAV, eight of which tested for in vitro isolation in three
      different sources of MDCC-MSB1 cell line and identified as lacking capacity to
      propagate in any of these cells, were compared to sequence data available for CAV
      strains propagated or not in cell culture. Alignment of the deduced aa resulted
      in a lack of singled out amino acid substitutions in the partial genomic
      sequences of Brazilian isolates that would entirely contrast them to viruses
      propagated in MSB-1 cells, indicating that the combined VP1, VP2 and VP3
      substitutions observed may not entirely account as sole determinants of CAV
      isolation and propagation in MDCC-MSB-1 cells.

PMID- 17196654
TI  - Differential effects of paraquat on oxidative stress parameters and polyamine
      levels in two freshwater invertebrates.
AB  - Paraquat is still a widely used herbicide in several countries. Its toxic action
      on plants occurs through a one-electron reduction interfering with the
      photosynthesis process. By a similar reaction, the herbicide may induce
      peroxidation processes in non-target animal species. Furthermore, paraquat may
      interfere with the cellular transport of polyamines. The aim of this work was to
      investigate some aspects related to paraquat-induction of oxidative stress
      (lipoperoxidation, enzymatic activities of catalase and superoxide dismutase) and
      also the levels of polyamines (putrescine, spermidine and spermine) in two
      species of freshwater invertebrates, the oligochaete Lumbriculus variegatus and
      the gastropod Biomphalaria glabrata. The results showed that both organisms
      elicited differential responses. In addition, the data suggested that polyamines
      may play an important role against lipoperoxidation processes.

PMID- 17196656
TI  - Distribution and possible source of trace elements in the sediment cores of a
      tropical macrotidal estuary and their ecotoxicological significance.
AB  - The paper presents the first document regarding concentration, distribution and
      possible sources of selected trace elements (Cu, Fe, Mn, Zn, Cr, Co, Ni, Pb, Al,
      B and Ba) in core sediments (<63 micro particle size) from the lower stretch of
      Hugli (Ganges) estuary, northeast coast of Bay of Bengal by ICP-AES and EDXRF to
      evaluate geochemical processes influencing their distribution and possible
      environmental consequences. The levels of elements showed a wide range of
      variations in different core depths, in upper and lower intertidal zones as well
      as among three sampling stations. The most interesting feature of the study is
      the downward increase of concentrations of majority of the elements reaching
      overall maximum values at a depth of 20-28 cm in upper littoral zone of the site
      located in the extreme downstream stretch of the estuary. Values of organic
      carbon showed very strong positive correlations with most of the elements as
      revealed by correlation matrix (r) values. The interelemental relationship
      revealed the identical behavior of element during its transport in the estuarine
      environment. The overall variation in concentration can be attributed to
      differential discharge of untreated effluents originating from industrial,
      agricultural, and aquacultural sources as well as from domestic sewage along with
      the fishing and boating activities. The resulting compositional dataset was
      tested by principal component analyses and cluster analyses. Pollution load index
      (PLI) and index of Geoaccumulation (Igeo) revealed overall low values but the
      enrichment factors (EFs) for Pb were typically high for all the stations. The
      mean concentrations of Zn and to some extent Cu exceeded the Effects Range-Low
      (ER-L) values in the majority of the cases indicating that there may be some
      ecotoxicological risk to organisms living in sediments. The concentration of the
      trace elements reported in this work is useful as baselines for comparison in
      future sediment quality studies.

PMID- 17196657
TI  - Evidence for preferential Ig gene usage and differential TdT and exonuclease
      activities in human naive and memory B cells.
AB  - Memory B cells and the antibodies they encode are important for protective
      immunity against infectious pathogens. Characterization of naive and memory B
      cell antibody repertoires will elucidate the molecular basis for the generation
      of antibody diversity in human B cells and the optimization of antibody
      structures that bind microbial antigens. In this study we aimed to investigate
      the influence of antigenic selection on the antibody genes of the two CD27+
      memory B cell subsets, comparing them with the naive repertoire in CD27- cells.
      We analyzed and compared the Ig heavy chain gene transcripts in three recently
      defined circulating naive and memory B cell subsets (CD19+IgD+CD27- [naive],
      CD19+IgD+CD27+ [un-class-switched memory] or CD19+IgD- CD27+ [class-switched
      memory]) at the single cell level. We found similar biased patterns of variable,
      diversity and joining heavy chain gene usages in all three groups of cells.
      CD19+IgD+CD27+ memory B cells harbored as diverse an antibody gene repertoire as
      CD19+IgD-CD27+ memory B cells. Interestingly, CD19+IgD+CD27+ memory B cells
      possessed a lower frequency of somatic mutations, a higher incidence of
      exonuclease activity at the 3' end of D regions, and a lower frequency of N and P
      nucleotide additions at both VH-D and D-JH junctions of CDR3 regions compared to
      CD19+IgD-CD27+ memory B cells. These data suggest distinct functional mechanisms
      underlying selection of this unique subset of un-class-switched memory B cells.

PMID- 17196659
TI  - Synthesis, DNA-binding and photocleavage studies of cobalt(III) mixed-polypyridyl
      complexes: [Co(phen)(2)(dpta)](3+) and [Co(phen)(2)(amtp)](3+).
AB  - Two novel cobalt(III) mixed-polypyridyl complexes [Co(phen)(2)(dpta)](3+) and
      [Co(phen)(2)(amtp)](3+) (phen=1,10-phenanthroline, dpta=dipyrido-[3,2-a;2',3'-c]-
      thien-[3,4-c]azine, amtp=3-amino-1,2,4-triazino[5,6-f]1,10-phenanthroline) have
      been synthesized and characterized. The interaction of these complexes with calf
      thymus DNA was investigated by spectroscopic, cyclic voltammetry, and viscosity
      measurements. Results suggest that the two complexes bind to DNA via an
      intercalative mode. Moreover, these Co(III) complexes have been found to promote
      the photocleavage of plasmid DNA pBR322 under irradiation at 365nm. The mechanism
      studies reveal that hydroxyl radical (OH()) is likely to be the reactive species
      responsible for the cleavage of plasmid DNA by [Co(phen)(2)(dpta)](3+) and
      superoxide anion radical (O(2)(-)) acts as the key role in the cleavage reaction
      of plasmid DNA by [Co(phen)(2)(amtp)](3+).

PMID- 17196658
TI  - Cloning, promoter analysis and expression in response to bacterial exposure of
      sea bass (Dicentrarchus labrax L.) interleukin-12 p40 and p35 subunits.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine pivotal in resistance to
      microbial and viral infections. In the search for immunoregulatory genes in sea
      bass the genes for the two IL-12 subunits p40 and p35 were cloned and sequenced.
      Molecular characterization of these two genes was performed at both the cDNA and
      genomic levels. Sea bass IL-12 p40 and p35 conserve most cysteines involved in
      the intra-chain disulfide bonds of human IL-12 subunits as well as the important
      structural residues for human IL-12 heterodimerization. The gene organization of
      sea bass IL-12 p40 is similar to the human orthologue, whilst the sea bass IL-12
      p35 gene structure, as reported for pufferfish, differs from the human one in
      containing an additional exon and lacking a second copy of a duplicated exon
      present in the mammalian genes. The promoter analysis of both sea bass and
      pufferfish IL-12 genes showed the presence of the main cis-acting elements
      involved in the transcriptional regulation of human and mouse orthologues. The
      involvement of IL-12 in sea bass anti-bacterial immune responses was demonstrated
      by investigating the expression profiles of IL-1beta, IL-12 p40 and p35 in the
      head-kidney and spleen following intraperitoneal injection of UV-killed and live
      Photobacterium damselae ssp. piscicida (Phdp). Finally, the importance of nuclear
      factor (NF)-kappaB on UV-killed Phdp-induced IL-12 p40 and p35 gene transcription
      was shown by the use of pyrrolidine dithiocarbamate (PDTC).

PMID- 17196661
TI  - Chromatography-based on- and in-line pre-concentration methods in capillary
      electrophoresis.
AB  - Capillary electrophoresis (CE) poses unique challenges in many different
      analytical applications, mainly to biological and complex samples and when only
      small amounts of sample are available, due to its low sample consumption. As a
      consequence, poor limits of detection are usually observed with this technique,
      especially with UV photodetectors. Minimal or no sample treatment is desirable in
      any analytical method to avoid external sources of contamination or errors and to
      provide a high throughput. On- and in-capillary sample pre-concentration
      strategies, based on solid-phase extraction (SPE) technology can take advantage
      of both techniques (SPE and CE), while avoiding sample contamination and tedious
      manipulations when the sample amount is an issue. Moreover, the combination can
      provide two-dimensional separations. This review collects the most recent
      strategies that merge SPE technology built on- and in-capillary pre-concentration
      for increasing sensitivity and/or selectivity.

PMID- 17196660
TI  - Usefulness of the 5' region of the cDNA encoding acidic ribosomal phosphoprotein
      P0 conserved among rats, mice, and humans as a standard probe for gene expression
      analysis in different tissues and animal species.
AB  - Housekeeping genes are often used as internal standards for gene expression
      analysis. When steady-state transcript levels of 4 typically used housekeeping
      genes, i.e., beta-actin, glyceraldehyde 3-phosphate dehydrogenase, cyclophilin,
      and acidic ribosomal phosphoprotein P0 (36B4), were evaluated in various rat
      tissues, the 36B4 gene seemed to be the most suitable as a standard to compare
      the expression levels of genes among different tissues. Next, for possible
      quantitative comparison of the expression level of this gene among different
      animal species, we compared the nucleotide sequence of the cDNA of 36B4 among
      rats, mice, and humans. As a result, highly conserved regions showing more than
      97.5% identities were observed in the 5' portion of its open reading frame. When
      samples of synthesized mRNA encoding rat, mouse, and human 36B4 were hybridized
      with the entire cDNA encoding rat 36B4 as a probe, hybridization signals of mRNAs
      of mouse and human 36B4 were much weaker than those of mRNA encoding rat 36B4.
      However, when they were hybridized with an oligonucleotide probe corresponding to
      the highly conserved regions, they showed similar signal intensities. Thus, these
      highly conserved regions of the cDNA encoding 36B4 were concluded to be an
      effective standard for use in gene expression analysis.

PMID- 17196662
TI  - Psychosomatic characterization of adjustment disorders in the medical setting:
      some suggestions for DSM-V.
AB  - BACKGROUND: Adjustment disorders have been found to be the most frequent
      psychiatric diagnosis in the medically ill. Problems have been raised, however,
      as to their clinical value. The aim of the study was to characterize the
      psychosomatic features of adjustment disorders. METHODS: One hundred patients
      with medical illness and a diagnosis of adjustment disorder according to DSM-IV
      criteria were interviewed according to the Diagnostic Criteria for Psychosomatic
      Research (DCPR) system, consisting of 12 clusters. RESULTS: A considerable
      overlap was shown between adjustment disorders and DCPR clusters related to
      abnormal illness behavior (health anxiety, tanatophobia, nosophobia and illness
      denial) (54%), somatization (functional somatic symptoms secondary to a
      psychiatric disorder, persistent somatization, conversion symptoms and
      anniversary reaction) (37%) and demoralization (33%). Only 13 of the patients
      with adjustment disorders did not present any DCPR syndromes. LIMITATIONS: The
      study is cross-sectional and does not allow to determine the prognostic features
      of DCPR categorization. CONCLUSION: The clinical information which derives from
      the concomitant application of the DCPR might improve and make more specific the
      treatment of patients with adjustment disorders.

PMID- 17196663
TI  - Examining the relationship between antenatal anxiety and postnatal depression.
AB  - BACKGROUND: Antenatal anxiety has received increased attention with regards to
      both its impact on infant outcomes and as a risk factor for postnatal depression.
      The measurement of anxiety in the perinatal setting, however, has proven to be
      challenging. The aims of the present study are to: determine whether antenatal
      anxiety as measured by the Brief Measure of Worry Severity (BMWS) is a
      significant predictor of postnatal depression (PND); examine the psychometric
      properties of a new measure of anxiety - the BMWS - in an antenatal sample; and
      examine the comparative capacity of the BMWS to the Speilberger State Trait
      Anxiety Inventory (STAI) in predicting PND. METHOD: A sample of 748 women
      completed the BMWS and STAI during the third trimester of pregnancy and returned
      the Edinburgh Postnatal Depression Scale (EPDS) at 8 weeks postpartum. RESULTS:
      Women with high antenatal anxiety on the BMWS were 2.6 times more likely to have
      probable PND than those with low scores, even after controlling for confounding
      factors, including level of antenatal depression on the EPDS. In contrast, the
      STAI was no longer a significant predictor of PND after controlling for these
      variables. The BMWS has good construct validity, with scores on this scale
      correlating strongly with scores on other measures of anxiety, depression and
      perinatal risk. LIMITATIONS: When compared to those who participated in the
      follow-up at 8 weeks postnatally, those who did not participate appeared to be at
      greater risk of developing PND, raising the possibility of attrition bias within
      this sample. CONCLUSIONS: The findings from this study suggest that the BMWS has
      utility in measuring antenatal anxiety in both clinical and research settings and
      that antenatal anxiety is an important precursor of PND.

PMID- 17196664
TI  - Clinical efficacy and cognitive side effects of bifrontal versus right unilateral
      electroconvulsive therapy (ECT): a short-term randomised controlled trial in
      pharmaco-resistant major depression.
AB  - BACKGROUND: In most studies right unilateral electroconvulsive therapy (ECT) has
      been shown to cause fewer cognitive side effects but less antidepressant efficacy
      compared with bi(fronto)temporal ECT at certain intensities. AIMS: To compare the
      short-term efficacy and side effects of right unilateral ECT and bifrontal ECT.
      METHODS: In a double-blind randomised controlled clinical trial, 92 patients
      diagnosed with pharmaco-resistant major depression received either six right
      unilateral ECT treatments (250% stimulus intensity of titrated threshold) or six
      bifrontal ECT (150% of threshold) treatments over a 3-week period. Concomitant
      psychotropic medications were continued during ECT treatments. The severity of
      depression and cognitive status was assessed prior to the first ECT and one day
      after the sixth ECT using the 21-item Hamilton Depression Rating Scale and the
      modified Mini Mental State Examination. RESULTS: Eight patients did not complete
      the course of the study due to minor side effects or withdrawal of consent. The
      mean Hamilton Depression score decreased from 27 to 17 points in both groups of
      46 patients, resulting in 12 responders (primary endpoint defined as a decrease
      >50%) in each patient group (95% confidence interval for the odds ratio from 0.35
      to 2.8). There was no reduction in the modified Mini Mental State score (mean
      score 86 of 100 points). CONCLUSIONS: Both bifrontal and right unilateral
      electrode placements in ECT were reasonably safe and moderately efficacious in
      reducing symptoms of pharmaco-resistant major depression.

PMID- 17196665
TI  - Toll-like receptor 3 agonist induces impairment of uterine vascular remodeling
      and fetal losses in CBA x DBA/2 mice.
AB  - The objective of this study was to examine the expression of Toll-like receptor
      (TLR) 3 at the maternal-fetal interface and determine whether exposure to TLR3
      agonist would induce an innate immune response and trigger pregnancy loss. To
      address this, abortion-prone male DBA/2J mated-CBA/J female mice were given
      polyinosinic-polycytidylic acid (poly I:C; 10 microg/g body weight, i.p.) or PBS
      at gestation day (gd) 6.5. All implantation sites appeared viable at gd 7.5 when
      endometrium was dissected for immunohistological examination. It was noted that
      poly I:C treatment increased fetal losses to 40.2+/-1.7% at midgestation stage
      compared with control animals (11.0+/-3.0%). It was observed also that the ratio
      of vessel to lumen area significantly increased at gd 10.5 and gd 12.5 after poly
      I:C treatment, indicating that the spiral artery (SA) modification was impaired.
      Meanwhile, 24h after poly I:C injection, expression of TLR3 was markedly elevated
      within decidua basalis (DB), and endometrial TNF-alpha increased 2.7-fold but IFN
      gamma remained unchanged in homogenized endometrium. These results suggest that
      enhanced TNF-alpha expression in endometrial stroma may play a critical role in
      inflammatory factor production and impairment of uterine spiral artery remodeling
      in the pregnancy failure of CBA x DBA/2 mating.

PMID- 17196666
TI  - CD4+ T cells from Copolymer-1 immunized mice protect dopaminergic neurons in the
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.
AB  - Adoptive transfer of lymphoid cells from Copolymer 1 (Cop-1) immunized mice leads
      to T cell accumulation within the substantia nigra, modulation of microglial
      responses, upregulation of glial cell derived neurotrophic factor, and protection
      of the nigrostriatum following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) intoxication. We now demonstrate that T cells isolated from lymph nodes
      and spleens of Cop-1 immunized animals protect the nigrostriatal system from MPTP
      induced neurodegeneration in a dose-dependent manner. CD4+ T cells elicited the
      most significant neuroprotective response while high titers of anti-Cop-1
      antibodies showed no effect. These data further support the use of
      immunomodulatory strategies for Parkinson's disease.

PMID- 17196668
TI  - Ingested (oral) SIRS peptide 1-21 inhibits acute EAE by inducing Th2-like
      cytokines.
AB  - OBJECTIVE: Ingested type I IFN inhibits clinical attacks, relapses and
      inflammation in murine chronic relapsing EAE by inhibiting Th1-like cytokines.
      Type I IFN activates human suppressor T cells that produce SIRS. METHODS: We
      examined whether oral (ingested) SIRS peptide inhibits EAE by decreasing Th1-like
      cytokines. RESULTS: Parenteral SIRS peptide 1-21 showed a significant inhibition
      of disease severity in murine EAE. Ingested SIRS peptide at 10 and 100 microg
      SIRS peptide showed a significant inhibition of disease severity but also a
      prolonged delay in the onset of disease compared to placebo. There were
      significantly less inflammatory foci in the SIRS peptide fed group compared to
      the control mock fed group. Splenocytes from SIRS peptide 1-21 fed mice showed
      increased production of Th2-like CD30L, IL-13, TCA-3 cytokines/chemokines and
      decreased production of Th1-like cytokine lymphotactin. INTERPRETATION: Ingested
      (oral) SIRS peptide significantly inhibits both clinical EAE and inflammation
      predominately via counter-regulatory type 2-like cytokines/chemokines IL-13,
      CD30L and TCA-3.

PMID- 17196669
TI  - Soluble TNFR1 inhibits the development of experimental autoimmune neuritis by
      modulating blood-nerve-barrier permeability and inflammation.
AB  - The role of TNFalpha/LTalpha during EAN induced by active immunization with
      peripheral nerve myelin was examined by administering a recombinant soluble
      chimeric form of human TNF receptor 1 (TNFR1-IgG). TNFalpha and LTalpha do not
      directly contribute to neurological deficit during EAN since treatment with TNFR1
      IgG after onset failed to alter the course of disease. Prophylaxis with a single
      dose of TNFR1-IgG delayed the onset of EAN and was accompanied initially by
      inhibition of blood-nerve-barrier permeability and inflammation. Subsequently,
      the number of infiltrating macrophages and blood-nerve-barrier permeability
      increased but the disease symptoms remained mild for five days (on average a limp
      tail) after which severe EAN developed. The antibody titer to peripheral nerve
      myelin was unaltered by prophylaxis with TNFR1-IgG. The markedly altered tempo of
      disease onset after TNFR1-IgG prophylaxis indicates that TNFalpha and/or LTalpha
      have a key role in the development of blood-nerve-barrier permeability and the
      coupling of macrophage activation and recruitment to peripheral nerve pathology
      during EAN.

PMID- 17196670
TI  - Does the vagus nerve mediate the effects of polyunsaturated fatty acid treatment
      on behavioral, neuroendocrine and cytokine changes elicited by exogenous
      interleukin-1beta challenge?

PMID- 17196667
TI  - Inflammation, demyelination, neurodegeneration and neuroprotection in the
      pathogenesis of multiple sclerosis.
AB  - Although axonal loss has been observed in demyelinated multiple sclerosis (MS)
      lesions, there has been a major focus on understanding mechanisms of
      demyelination. However, identification of markers for axonal damage and
      development of new imaging techniques has enabled detection of subtle changes in
      axonal pathology and revived interest in the neurodegenerative component of MS.
      Axonal loss is generally accepted as the main determinant of permanent clinical
      disability. However, the role of axonal loss early in disease or during relapsing
      remitting disease is still under investigation, as are the interactions and
      interdependency between inflammation, demyelination, neurodegeneration and
      neuroprotection in the pathogenesis of MS.

PMID- 17196671
TI  - Canal atresia: "surgery or implantable hearing devices? The expert's question is
      revisited".
AB  - OBJECTIVES: (1) Evaluate hearing results in patients managed with external
      auditory canal reconstruction; (2) compare results to the expectations from
      treatment with surgical; placement of an osteo-integrated bone-conduction device
      (BAHA system); (3) assess complications of both interventions; (4) evaluate the
      medical cost-effectiveness of each avenue of management at 2005 rates for
      billings based upon relative value units (RVUs). METHODS: (1) Retrospective chart
      review for 36 ears in 29 pediatric patients who underwent surgical canal
      reconstruction at a tertiary-care pediatric hospital in a major urban center with
      assessment of management techniques and surgical and audiologic outcomes. (2)
      Retrospective chart review of six pediatric patients who underwent BAHA placement
      in a major urban center with assessment of management techniques and surgical and
      audiologic outcomes. (3) Cost reassessment at 2005 billings rates based upon RVUs
      for canal reconstruction versus BAHA system and comparative analysis. RESULTS:
      (1) The average post-operative hearing loss in the right ear was 34.3 dB left ear
      was 31.6 dB. The average gain per ear was 17.3 dB. (2) Twenty-seven (93%) of EAC
      reconstruction patients required some form of amplification post-operatively. (3)
      Data available for three of the BAHA patients reflected the predicted average
      gain in dB (predicted 34.3 dB, observed 31.8 dB). (4) Early complications of
      canal reconstruction included removal of the packing by the patient, post
      operative bleeding and post-operative hematoma. (5) Late complications included
      recurrent canal stenosis, recurrent otitis externa, canal prolapse and canal
      cholesteatoma. (6) Uncomplicated external auditory canal reconstruction cost
      $51,505.98 or $2909.94/dB of hearing gain based upon billings fro RVUs. (7)
      Uncomplicated two-staged BAHA system placement cost $42,448.85 or $1237.57/dB of
      hearing gain based upon billings for RVUs. (8) Uncomplicated single-staged BAHA
      system placement cost $28,341.00 or $826.27/dB of hearing gain based upon
      billings for RVUs. CONCLUSIONS: Study results indicate that even with significant
      investments in EAC reconstruction, most patients still required some form of
      amplification. There are also significant risks of early and late complications
      from the reconstructive procedure. Studies indicate and our results support that
      the osteo-integrated bone-conduction device (BAHA system) can achieve truly
      acceptable hearing (<or=15 dB) in school-aged children with normal bone curves,
      and it can match the bone-curves for children with sensorineural hearing loss.
      The two-staged BAHA system placement may be provided at almost one-third the cost
      to the medical system, on a decibel-for-decibel basis. The single-stage BAHA
      system placement yields even greater cost savings at just over one-quarter of the
      cost of surgical EAC reconstruction on a decibel-for-decibel basis. Additionally,
      there are fewer complications and fewer follow-up visits for the care of the
      implant system. This is an added value to the parents and patient for the savings
      in opportunity costs related to the lost time at work and school for office
      visits and peri-operative care. Overall, it appears that osteo-integrated bone
      conduction devices may provide a higher quality of outcome for patients while
      resulting in significant economic savings.

PMID- 17196672
TI  - Caloric and vestibular evoked myogenic potential tests in evaluating children
      with benign paroxysmal vertigo.
AB  - OBJECTIVE: This study applied caloric and vestibular evoked myogenic potential
      (VEMP) tests to evaluate whether children with benign paroxysmal vertigo (BPV)
      shares similar vestibular features with basilar type migraine. METHODS: Twenty
      subjects of each group including healthy and BPV children were enrolled in this
      study. Each subject underwent audiometry, caloric and VEMP tests. Diagnosis of
      BPV was based on the International Classification of Headache Disorder, second
      edition. RESULTS: All BPV children had normal hearing, bilaterally. Caloric test
      revealed normal responses in 13 patients and abnormal responses in 7 patients
      (35%). VEMP test showed 50% abnormality in BPV children, including absent and
      delayed responses. However, when results of caloric and VEMP testing were
      considered together, 70% of BPV children had abnormality, exhibiting non
      significant difference compared with 75% abnormality in basilar type migraine.
      CONCLUSIONS: A combination of caloric and VEMP results reveals higher abnormality
      (70%) in BPV children, sharing similar features with basilar type migraine in
      adults, given the similarity of the two disorders. Thus, caloric and VEMP tests
      may serve as supplementary diagnostic tools in evaluating children with BPV.

PMID- 17196674
TI  - Contrasting effects of heavy metals and hydrocarbons on larval settlement and
      juvenile survival in sponges.
AB  - Metals and polycyclic aromatic hydrocarbons (PAHs) contaminate sediments and
      waters of coastal areas threatening early stages of invertebrate development.
      Effects on these stages may largely determine the decline and even disappearance
      of invertebrate populations in polluted environments. Our study aimed to
      determine the possible influence of metals (Cu and Cd) and PAHs on larval
      settlement and consecutive survival of two widespread sponges of the
      Mediterranean: Crambe crambe and Scopalina lophyropoda. Larvae of both species
      were exposed to Cu and Cd for a short period during 1 week, and settlement and
      following (6 months) survival of juvenile were monitored. Short exposures to
      copper and cadmium at the concentrations used did not affect C. crambe settlement
      compared with SW control, and no effect on consecutive survival of juveniles was
      observed. In contrast, short pulses of copper and cadmium at the concentrations
      used enhanced Scopalina lophyropoda settlement and did not affect the consecutive
      survival of juveniles with respect to SW controls. Furthermore, experiments
      designed to assess the effects of short exposures to PAHs and the combined effect
      of contamination by Cu(2+) and PAHs on larval settlement, were conduced during 10
      days on C. crambe larvae. Hydrocarbons, differently than copper and cadmium,
      inhibited the settlement of sponge larvae to a certain extent. The synergetic
      negative effect of copper and hydrocarbons on C. crambe settlers may cause a
      decline of populations in areas with both sources of contamination. The present
      study provides the only available data on toxicity of copper, cadmium and
      hydrocarbon toxicants on sponge larval settlement.

PMID- 17196673
TI  - Molecular beacon real-time PCR detection of swine viruses.
AB  - Rapid and reliable detection of viral pathogens is critical for the management of
      the diseases threatening the economic competitiveness of the swine farming
      industry worldwide. Molecular beacon assays are one type of real-time polymerase
      chain reaction (PCR) technology capable of fast, specific, sensitive, and
      reliable viral detection. In this paper, the development of molecular beacon
      assays as novel tools for the rapid detection of Aujeszky's disease virus,
      African swine fever virus, porcine circovirus type 2 and porcine parvovirus is
      described. The assays are capable of rapidly detecting 2 x 10(1) copies of target
      and are linear between 2 x 10(9) and 2 x 10(2) copies. They can detect virus
      specifically in clinical samples such as whole blood, serum and tissue. In
      comparison to conventional PCR they are either as sensitive or more sensitive. As
      such these molecular beacon assays represent a powerful tool for the detection of
      these viruses in swine.

PMID- 17196675
TI  - Comparative transcriptomal analysis of isogenic Plasmodium falciparum clones of
      distinct antigenic and adhesive phenotypes.
AB  - Antigenic variation is a survival mechanism developed by the malaria parasite
      Plasmodium falciparum in order to allow for the establishment of a chronic
      infection. Here we have studied clonal differences in the transcriptomes of two
      isogenic P. falciparum clones (3D7S8.4 and 3D7AH1S2) of distinct adhesive and
      antigenic phenotypes employing a P. falciparum 70-mer oligonucleotide microarray.
      Fifteen transcripts were highly differentially expressed (greater than a 5-fold
      change) with five transcripts upregulated in 3D7AH1S2 compared to 3D7S8.4, and
      ten downregulated. Identified genes encode apical organellar (Gbph2, GBP-related
      antigen), cell cycle and DNA/RNA processing (SERA-5, RNA-methylase), cell-rescue,
      defense/virulence (RESA-2, RIFIN, PfEMP1) and hypothetical proteins (PFB0115w,
      PFI1445w, MAL13P1.121). A number of short and full-length var transcripts were
      differentially expressed between the clones but one full-length transcript was
      dominant in both rings and trophozoites (PFD0630c versus PFF0845c). Distinct
      members of two other variant gene families (phist-a and rif-like), scattered over
      the subtelomeric areas of the 14 chromosomes, were also found to be clonally and
      developmentally expressed. Three sibling-clones of 3D7AH1S2 (3D7AH1S1, -S3, -S4)
      were further studied for the expression of transcripts upregulated in 3D7AH1S2
      compared to 3D7S8.4. Individual var and phist-a genes were found expressed in all
      of the clones while the expression of a rif-like gene and gbph2 varied in-between
      the clones. The present data provides evidence for complex transcriptional
      differences between closely related isogenic P. falciparum of distinct adhesive
      and antigenic characteristics.

PMID- 17196676
TI  - Differential sympathetic and angiotensinergic responses in rats submitted to low-
      or high-salt diet.
AB  - The present study was designed to evaluate, in Wistar rats, the effect of high-
      or low-salt diet on the hemodynamic parameters and on the renal and lumbar
      sympathetic nerve activity. The renal gene expression of the renin angiotensin
      system components was also evaluated, aiming to find some correlation between
      salt intake, sodium homeostasis and blood pressure increase. Male Wistar rats
      received low (0.06% Na, TD 92141-Harlan Teklad), a normal (0.5% Na, TD 92140), or
      a high-salt diet (3.12% Na, TD 92142) from weaning to adulthood. Hemodynamic
      parameters such as cardiac output and total peripheral resistance, and the renal
      and lumbar sympathetic nerve activity were determined (n=45). Plasma renin
      activity, plasma and renal content of angiotensin (ANG) I and II, and the renal
      mRNA expression of angiotensinogen, renin, AT1 and AT2 receptors were also
      measured (n=24). Compared to normal- and low-salt diet-, high-salt-treated rats
      were hypertensive and developed an increase (P<0.05) in total peripheral
      resistance and lumbar sympathetic nerve activity. A decrease in renal renin and
      angiotensinogen-mRNAs and in plasma ANG II and plasma renin activity was also
      found in salt overloaded animals. The renal sympathetic nerve activity was higher
      (P<0.05) in low- compared to high-salt-treated rats, and was associated with an
      increase (P<0.05) in renal ANG I and II and with a decrease (P<0.05) in AT2 renal
      mRNA. Plasma ANG I and II and plasma renin activity were higher in low- than in
      normal-salt rats. Our results show that increased blood pressure is associated
      with increases in lumbar sympathetic nerve activity and total peripheral
      resistance in high-salt-treated rats. However, in low-salt-treated rats an
      increase in the renal sympathetic nerve was correlated with an increase in the
      renal content of ANG I and II and with a decrease in AT2 renal mRNA. These
      changes are probably in favor of the antinatriuretic response and the sodium
      homeostasis in the low-salt group.

PMID- 17196677
TI  - Alterations in gene expression in the testis of angiotensin-(1-7)-receptor Mas
      deficient mice.
AB  - The Mas protooncogene encodes a G-protein coupled receptor with seven trans
      membrane domains and was recently described as a receptor for angiotensin-(1-7).
      Mas is highly expressed in testis and brain of rodents, whereas its expression in
      testis is localized to Leydig cells, being upregulated during puberty. Although
      the expression of this receptor in testis is strongly ontogenetically controlled
      and cell type-specific, Mas-deficient mice are fertile. To identify genes of
      which the expression is affected by the deletion of Mas, we performed
      differential gene expression profiling. Testis-RNA of Mas-knockout mice on a
      C57Bl/6 background vs. testis-RNA of C57Bl/6 wild type mice were analyzed on an
      Affymetrix Murine Genome U74v2 GeneChip probing >12,000 transcripts. The
      microarray identified 67 transcripts, which were downregulated in Mas-deficient
      mice and 65 genes, which were upregulated. The analysis of 132 differentially
      expressed genes by a Gene Ontology Mining Tool revealed genes with activities in
      mitochondria being overrepresented in the set of significantly affected genes.
      For some selected genes, the results were verified by a specific real time PCR.
      Three of these genes, coding for proteins involved in mitochondrial function and
      steroidogenesis, become henceforth targets for our continuing search for the
      physiological function of Mas in testis.

PMID- 17196678
TI  - Solution structure of DNA/RNA hybrid duplex with C8-propynyl 2'-deoxyadenosine
      modifications: Implication of RNase H and DNA/RNA duplex interaction.
AB  - Solution structures of DNA/RNA hybrid duplexes, d(GCGCA*AA*ACGCG):
      r(cgcguuuugcg)d(C) (designated PP57), containing two C8-propynyl 2'
      deoxyadenosines (A*) and unmodified hybrid (designated U4A4) are solved. The C8
      propynyl groups on 2'-deoxyadenosine perturb the local structure of the hybrid
      duplex, but overall the structure is similar to that of canonical DNA/RNA hybrid
      duplex except that Hoogsteen hydrogen bondings between A* and U result in lower
      thermal stability. RNase H is known to cleave RNA only in DNA/RNA hybrid
      duplexes. Minor groove widths of hybrid duplexes, sugar puckerings of DNA are
      reported to be responsible for RNase H mediated cleavage, but structural
      requirements for RNase H mediated cleavage still remain elusive. Despite the
      presence of bulky propynyl groups of PP57 in the minor groove and greater
      flexibility, the PP57 is an RNase H substrate. To provide an insight on the
      interactions between RNase H and substrates we have modeled Bacillus halodurans
      RNase H-PP57 complex, our NMR structure and modeling study suggest that the
      residue Gly(15) and Asn(16) of the loop residues between first beta sheet and
      second beta sheet of RNase HI of Escherichia coli might participate in substrate
      binding.

PMID- 17196679
TI  - Activation of p38MAPK by repetitive low-grade oxidative stress leads to pro
      survival effects.
AB  - V79 lung fibroblasts were subjected to repetitive oxidative stress in culture
      through exposures to 30 microM H2O2 for 4 weeks. Within the first week of
      treatment p38MAPK became dually phosphorylated and became increasingly
      phosphorylated during the 4-week stress period. Akt also became phosphorylated on
      Ser473 and Thr308 after the second week of treatment and remained phosphorylated
      throughout the study. NFkappaB p65 and IkappaB kinase (IKK) became phosphorylated
      and NFkappaB transcriptional activity became augmented during repetitive stress.
      Treatment of the cells concurrently with SB203580, a specific p38MAPK inhibitor,
      robustly blocked activation of NFkappaB transcriptional activity, phosphorylation
      of p65, and IKK but only partially blocked Akt phosphorylation. Similar
      simultaneous treatment with PI-3 kinase inhibitor LY294002 prominently blocked
      Akt phosphorylation. Pre-exposure to short interfering RNA (si RNA ) to p38MAPK
      resulted in a complete blockage of the NFkappaB p65 and IKK phosphorylations as
      well as the anti-apoptotic influence induced by a single low dose of H2O2 but
      produced a partial obstruction of Akt phosphorylation. Repetitively stressed
      cells were found to be significantly resistant to apoptosis-inducing agents such
      as ultraviolet radiation (UVR) and mM H2O2. Concurrent treatment with SB203580
      almost completely restored the normal apoptotic response such as DNA
      fragmentation after UVR and mM H2O2. LY294002, a PI-3 kinase inhibitor and SN-50,
      an inhibitor of NFkappaB, produced partial restorations of the apoptotic
      response. We conclude that activation of p38MAPK by repetitive oxidative stress
      is the key event which through its command over down-stream survival elements
      such as Akt and NFkappaB controls the anti-apoptotic environment of the
      repetitively H2O2-stressed cells.

PMID- 17196680
TI  - Regulation of gene transcription by mitogen-activated protein kinase signaling
      pathways.
AB  - Mitogen-activated protein kinase (MAPK) signaling pathways are key mediators of
      eukaryotic transcriptional responses to extracellular signals. These pathways
      control gene expression in a number of ways including the phosphorylation and
      regulation of transcription factors, co-regulatory proteins and chromatin
      proteins. MAPK pathways therefore target multiple components of transcriptional
      complexes at gene promoters and can regulate DNA binding, protein stability,
      cellular localization, transactivation or repression, and nucleosome structure.
      Recent work has uncovered further complexities in the mechanisms by which MAPKs
      control gene expression including their roles as integral components of
      transcription factor complexes and their interplay with other post-translational
      modification pathways. In this review I discuss these advances with particular
      focus on how MAPK signals are integrated by transcription factor complexes to
      provide specific transcriptional responses and how this relates to cellular
      function.

PMID- 17196681
TI  - Genealogy of centenarians and their relatives: a study of 12 families.
AB  - The longevity is a complex phenomenon in which specific genetic properties seem
      to play a role. The present study intended to reconstruct the genealogical tree
      of 12 subjects, being residents of one Northern and one Southern province of
      Italy, in order to establish the longevity of the ancestors. Detailed studies
      have been performed in the registry offices and the historic archives. The
      research method started from the identification of the centenarians on the basis
      of the documentation of the relevant birth document, it was continued by
      identifying the documents of birth, marriages and death of the parents of the
      centenarians. This way we proceeded systematically backwards in time. In
      addition, we verified the medium life span of the Italian population in the given
      periods of time, when the centenarians and their ascending lines had lived. These
      results offer clear historic-statistical evidences for the genetic basis of
      longevity.

PMID- 17196683
TI  - Transradial coronary intervention without pre-screening for a dual palmar blood
      supply.
AB  - It is usual practice to determine the presence of collateral blood supply to the
      hand prior to radial artery cannulation. We propose that pre-screening for a dual
      palmar vascular supply is not necessary and the presence of a palpable radial
      pulse is sufficient to allow successful radial artery cannulation. We
      retrospectively analysed our interventional PTCA registry, including only
      patients who had a transradial procedure without being pre-screened with an
      Allen's test or plethysmography. We report our data including complications the
      day after the procedure and at 30 days, and provide an up to date discussion on
      the need to assess patients for a dual palmar blood supply prior to transradial
      intervention.

PMID- 17196684
TI  - Strong suppression of high-sensitivity C-reactive protein level and its mediated
      pro-atherosclerotic effects with simvastatin: in vivo and in vitro studies.
AB  - BACKGROUND: We hypothesize that high-sensitivity C-reactive protein (hs-CRP)
      levels and cell adhesion molecules (CAMs) significantly reflect serial changes in
      patients with atherosclerotic-risk factors undergoing simvastatin therapy. We
      further hypothesize that the site specificity of CRP on the expression of CAMs,
      which can be inhibited by simvastatin, is in the cytoplasm of endothelial cells
      (EC). METHODS AND RESULTS: Serum hs-CRP levels and vascular (V) CAM-1 were
      measured (on days 0, 30, 90, 180 and 270) in 59 study subjects with at least one
      atherosclerotic-risk factor and low density lipoprotein (LDL) cholesterol >100
      gm/dL. Simvastatin (40 mg/day) was given to each study subjects for 6 months. The
      inflammatory mediators were evaluated in 30 healthy subjects. Human umbilical
      vein (HUV) ECs were incubated with 1) culture medium alone, 2) added CRP for
      stimulation, and 3) simvastatin for 4 h before CRP was added. The hs-CRP and VCAM
      1 levels were significantly higher on day 0 in study subjects than in healthy
      subjects (all p<0.0001). These inflammatory markers declined to a significantly
      lower level on day 90 (all p<0.001) and to an even lower level by day 180 (all
      p<0.0001). After simvastatin therapy was withdrawn, the hs-CRP level was once
      again significantly higher on day 270 than on day 180 (p<0.05), but VCAM-1 did
      not differ between day 180 and day 270. 25 micromol/L simvastatin markedly
      suppressed the CRP effect on VCAM-1 and intercellular CAM-1 expressions of EC.
      Immunocytochemical staining identified CRP in HUVEC cytoplasm. However,
      pretreatment with simvastatin reduced the intensity of CRP in cytoplasm.
      CONCLUSIONS: CRP-mediated inflammation is inhibited by simvastatin.

PMID- 17196682
TI  - Comparative study of nicorandil and a spasmolytic cocktail in preventing radial
      artery spasm during transradial coronary angiography.
AB  - BACKGROUND: Radial artery spasm is one of the most common complications during
      coronary angiography via the transradial approach, causing patient discomfort or
      sometimes interrupting the procedure. This study was designed to compare the
      spasmolytic effect between nicorandil and a cocktail during transradial coronary
      angiography. METHODS: A randomized study to compare 4 mg of nicorandil and a
      cocktail (mixture of normal saline, 200 microg of verapamil) was performed in 150
      patients. We examined vasospasms of the radial artery that were expressed as
      stenosis of the radial artery vessel diameter after the procedure. RESULT: The
      reductions of systolic and diastolic blood pressures showed no significant
      differences between the two groups (15.4+/-11.5/7.7+/-7.8 mmHg for nicorandil and
      16.3+/-13.4/6.2 mmHg for cocktail). Both agents induced a significant radial
      artery vasodilation after transradial administration at proximal and mid segments
      (P < 0.001 for all). Nicorandil showed a significant increase of the mean change
      of the radial artery diameter compared to the cocktail at mid-segment (0.32+/
      0.23 mm for nicorandil and 0.24+/-0.15 mm for a cocktail, P < 0.05). There was no
      statistically significant difference between the two groups in radial artery
      spasm (50.7% vs. 52.0% in nicorandil and a cocktail, respectively) after
      catheterization. CONCLUSION: Nicorandil with vasodilator effects by a dual
      mechanism was effective as the cocktail in preventing radial artery spasm during
      transradial coronary angiography.

PMID- 17196686
TI  - Isolated single left coronary artery.
AB  - Single coronary artery is an extremely rare congenital anomaly with a very low
      incidence in the general population. We present a 65-year-old woman with atypical
      chest pain and a single left coronary artery discovered in the cath lab. No
      coronary lesions were found. Such anomaly has been previously described before
      only in twelve patients.

PMID- 17196685
TI  - Cumulative exercise-induced left ventricular systolic and diastolic dysfunction
      in hypertrophic cardiomyopathy.
AB  - The phenomenon of cumulative exercise-induced left ventricular function
      impairment was studied in 40 patients with non-obstructive hypertrophic
      cardiomyopathy with resting normal left ventricular function and no increase in
      ejection fraction on exercise. All patients underwent two symptom-limited
      exercise tests one-hour apart. Cumulative myocardial dysfunction was seen in 13
      patients (group I) but not in the remaining 27 patients (group II). During follow
      up, group I showed more commonly than group II a deterioration in symptoms (67%
      vs 22%, P=0.025) and left ventricular function (50% vs 9%, P=0.019). In
      conclusion, cumulative exercise-induced myocardial dysfunction can occur in
      hypertrophic cardiomyopathy and may be associated with clinical deterioration and
      worse outcome.

PMID- 17196688
TI  - Detection of cardiac small vessel disease by adenosine-stress magnetic resonance.
AB  - BACKGROUND: Patients testing positive for myocardial ischemia but without
      significant coronary artery (CA) stenosis in coronary angiography (CXA) are
      characterized as having "small vessel disease" (SVD). The aim of our study was to
      identify these patients by stress perfusion cardiac magnetic resonance (CMR).
      METHODS: 317 patients with suspected myocardial ischemia and clinical indication
      for CXA were scanned < 72 h before CXA in a whole-body 1.5T scanner. After 3 min
      of adenosine infusion (140 microg/kg/min), a myocardial first-pass perfusion
      sequence in 4-5 contiguous short-axis orientations using a Gadolinium-based
      contrast agent (0.1 mmol/kg) was performed. Images were analyzed qualitatively by
      two independent and blinded investigators. RESULTS: Perfusion deficits were
      detected in 93% of our patients. In 78% of patients with relevant perfusion
      delay, perfusion deficits extended to > 1/3 of the wall thickness in > or = 2
      myocardial segments, persisted for > 5 heartbeats and were regarded as relevant
      coronary macroangiopathy. All of these patients had significant CA stenosis (60%
      had luminal narrowing > 70% and 18% had 50-70%). 22% of the patients had
      perfusion deficits affecting < or = 1/3 of wall thickness with persistence for <
      or = 5 heartbeats and were regarded as having SVD. None of these patients had a
      CA stenosis of > 50% or received CA revascularization. These patients more
      frequently had hypertension (p<0.0001), diabetes (p<0.05) and circumferential
      perfusion deficits (p<0.0001) than other patients. CONCLUSION: Stress perfusion
      CMR allows non-invasive differentiation between patients with significant CA
      stenosis and patients with SVD caused by hypertension and/or diabetes based on
      the temporal and spatial extent of perfusion deficits. Patients with SVD more
      often have diffuse perfusion deficits with shorter persistence than patients with
      significant CA disease.

PMID- 17196689
TI  - Transcatheter closure of a non-restrictive patent ductus arteriosus with an
      Amplatzer muscular ventricular septal defect occluder.
AB  - We report on successful occlusion of a large unrestrictive PDA in an adult
      patient with pulmonary hypertension.

PMID- 17196687
TI  - Carotid artery intima-media thickness and cognition in cardiovascular disease.
AB  - BACKGROUND: Increased carotid artery intima-media thickness (IMT) is a non
      invasive marker of systemic arterial disease. Increased IMT has been associated
      with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and
      stroke. Given evidence of a relationship between cardiovascular health and
      attention-executive-psychomotor functioning, the purpose of this study was to
      examine IMT in relation to neuropsychological test performance in patients with a
      variety of cardiovascular diagnoses. METHODS: One hundred and nine participants,
      ages 55 to 85, underwent neuropsychological assessment and B-mode ultrasound of
      the left common carotid artery. IMT was calculated using an automated algorithm
      based on a validated edge-detection technique. The relationship between IMT and
      measures of language, memory, visual-spatial abilities and attention-executive
      psychomotor functioning was modeled using hierarchical linear regression analyses
      adjusted for age, education, sex, cardiovascular risk, current systolic blood
      pressure, and history of coronary artery disease (CAD). RESULTS: Increased IMT
      was associated with significantly lower performance in the attention-executive
      psychomotor domain (IMT beta=-0.26, p<.01), independent of age, education, sex,
      cardiovascular risk, current systolic blood pressure, and CAD (F(10,100)=3.61,
      p<.001). IMT was not significantly related to language, memory, or visual-spatial
      abilities. CONCLUSIONS: Our findings suggest that, in patients with
      cardiovascular disease, IMT may be associated with the integrity of frontal
      subcortical networks responsible for attention-executive-psychomotor performance.
      Future studies are needed to clarify the mechanisms by which IMT affects
      cognition and examine potential interactions between increased IMT and other
      measures of cardiovascular health such as blood pressure variability, cardiac
      systolic performance, and systemic perfusion.

PMID- 17196691
TI  - Variations in T-RFLP profiles with differing chemistries of fluorescent dyes used
      for labeling the PCR primers.
AB  - Culture independent molecular methods have emerged as indispensable tools for
      studying microbial community structure and dynamics in natural habitats, since
      they allow a closer look at microbial diversity that is not reflected by
      culturing techniques. Terminal Restriction Fragment Length Polymorphism (T-RFLP)
      analysis is one of the informative and widely used techniques for such studies.
      However, the method has a few limitations to predict microbial community
      structure with significant accuracy. One of the major limitations is variation in
      real Terminal Restriction Fragment (TRF) length and observed TRF length. In the
      present study we report the generation of TRF length variations using different
      fluorescent dyes to label the PCR primers. T-RFLP profiles generated from primers
      labeled with different dyes varied significantly and led to inconsistent
      microbial species identification. Occurrence of such variations can have serious
      consequences on interpretation of the T-RFLP profiles from environmental samples
      representing complex microbial community. Therefore, in a T-RFLP study, the
      primers and labeling dye system should be carefully evaluated and optimized for
      an individual community under investigation. Further, it would be recommended to
      establish a target gene library in parallel with T-RFLP analysis to facilitate
      the accurate prediction of microbial community structure.

PMID- 17196693
TI  - Alternative poly(A) site-selection regulates the production of alternatively
      spliced vesl-1/homer1 isoforms that encode postsynaptic scaffolding proteins.
AB  - The vesl-1/homer1 gene encodes a scaffold protein that interacts with several
      receptors to modulate synaptic functions. The gene also encodes two shorter forms
      that counteract the functions of the long form of Vesl. Expression of the shorter
      forms is driven by neural activities such as long-term potentiation. Here we
      analyzed the mechanism regulating vesl-1 alternative splicing. Each functional
      poly(A) site was in a different part of the 3'-terminal exon, with promoter
      proximal and promoter-distal sites at the end of exons corresponding to the short
      and long form Vesl-1, respectively. 3'-End-processing at proximal poly(A) site,
      specifically at the vesl-1M poly(A) site, was enhanced by extracellular stimuli,
      thereby switching transcription termination from promoter-distal to -proximal
      poly(A) site. This switch was not specifically coupled to the vesl-1 promoter and
      was independent of de novo protein synthesis. Analysis of transcripts from mini
      genes that mimic the structure of endogenous vesl-1 revealed that the vesl-1M
      poly(A) region plays a crucial role in switching to the alternative pre-mRNA
      splicing that is triggered by extracellular stimuli. Therefore, a 3'-end
      processing event regulates the neural activity-dependent alternative splicing of
      vesl-1. This is the first report of a gene in which alternative poly(A) site
      selection regulates alternative splicing in a protein synthesis-independent
      manner.

PMID- 17196692
TI  - Enhanced visualization of microbial biofilms by staining and environmental
      scanning electron microscopy.
AB  - Bacterial biofilms, i.e. surface-associated cells covered in hydrated
      extracellular polymeric substances (EPS), are often studied with high-resolution
      electron microscopy (EM). However, conventional desiccation and high vacuum EM
      protocols collapse EPS matrices which, in turn, deform biofilm appearances.
      Alternatively, wet-mode environmental scanning electron microscopy (ESEM) is
      performed under a moderate vacuum and without biofilm drying. If completely
      untreated, however, EPS is not electron dense and thus is not resolved well in
      ESEM. Therefore, this study was towards adapting several conventional SEM
      staining protocols for improved resolution of biofilms and EPS using ESEM. Three
      different biofilm types were used: 1) Pseudomonas aeruginosa unsaturated biofilms
      cultured on membranes, 2) P. aeruginosa cultured in moist sand, and 3) mixed
      community biofilms cultured on substrates in an estuary. Working with the first
      specimen type, a staining protocol using ruthenium red, glutaraldehyde, osmium
      tetroxide and lysine was optimized for best topographic resolution. A
      quantitative image analysis tool that maps relief, newly adopted here for
      studying biofilms, was used to compare micrographs. When the optimized staining
      and ESEM protocols were applied to moist sand cultures and aquatic biofilms, the
      smoothening effect that bacterial biofilms have on rough sand, and the roughening
      that aquatic biofilms impart on initially smooth coupons, were each quantifiable.
      This study thus provides transferable staining and ESEM imaging protocols
      suitable for a wide range of biofilms, plus a novel tool for quantifying biofilm
      image data.

PMID- 17196694
TI  - Water activity of bacterial suspension media unable to account for the
      baroprotective effect of solute concentration on the inactivation of Listeria
      monocytogenes by high hydrostatic pressure.
AB  - Inactivation of Listeria monocytogenes (10(8) CFU/ml) by high hydrostatic
      pressure (HHP) from 400 to 600 MPa at 25 degrees C for 10 min was investigated
      with various concentrations of sodium chloride, sucrose, and sodium phosphate
      buffer solutions. Sodium chloride significantly inhibited HHP-induced
      inactivation of L. monocytogenes at concentrations higher than 2.6 M. A low
      concentration of sodium chloride within 1.7 M had no effect on HHP-induced
      inactivation. Almost complete inactivation at relatively low sodium chloride
      concentration solution was observed with treatments above 500 MPa. Sucrose also
      significantly inhibited HHP-induced inactivation of L. monocytogenes when greater
      than 1.2 M sucrose solutions were used. HHP-treatment at 400 MPa reduced the
      number of L. monocytogenes in 1.2 M, 1.5 M, and 1.8 M sucrose solutions by 4.8,
      2.0, and 0.7 log cycles, respectively. Higher pressure did not yield significant
      reductions. Sodium phosphate buffer significantly inhibited HHP-induced
      inactivation of L. monocytogenes. In particular, 1 M phosphate buffer completely
      inhibited HHP-induced inactivation even at 600 MPa. HHP-treatment at 400 MPa
      reduced the number of L. monocytogenes in 0.1 M, 0.25 M, and 0.5 M phosphate
      buffer solutions by 5.6, 4.1, and 3.2 log cycles, respectively. The effect of HHP
      induced inactivation of L. monocytogenes in the three kinds of solution was
      evaluated by adjusting water activity (a(w)). However, the baroprotective effect
      differed depending on the kind of solute even at the same a(w). This result
      showed no consistent correlation between a(w) and solute concentration in terms
      of the baroprotective effect. As an alternative approach, saturation of
      suspension solution was used for evaluating the effect of HHP-induced
      inactivation of L. monocytogenes. As the saturation of suspension media
      increased, the effect of HHP-induced inactivation of L. monocytogenes decreased
      regardless of the kinds of solute. The saturation of solution would be an
      alternative parameter of inhibition in terms of HHP-induced inactivation of
      bacteria.

PMID- 17196695
TI  - Antimicrobial resistance of Yersinia enterocolitica strains from human patients,
      pigs and retail pork in Switzerland.
AB  - To obtain basic data for future resistance monitoring programs, 386 Yersinia
      enterocolitica strains from human patients, raw retail pork and pig feces were
      tested for their susceptibilities to 16 antimicrobial agents and two
      antimicrobial growth promoters (carbadox and olaquindox). No strains were
      resistant to ceftriaxone, cefuroxime, ciprofloxacine, gentamicin, kanamycin,
      neomycin or polymyxin. Although in Switzerland carbadox and olaquindox were used
      as growth promoters for pigs for over 25 years, all strains were susceptible to
      them. In contrast, there were high levels of resistance to ampicillin, cefalothin
      and amoxicillin/clavulanic acid. Less than 10% of clinical isolates and strains
      from pig feces were resistant to streptomycin, sulfonamide,
      trimethoprim/sulfamethoxazole, tetracyclin, trimethoprim and chloramphenicol, but
      strains from retail pork were all susceptible to these antimicrobial agents. This
      finding suggested that pork is probably not a major source of Y. enterocolitica
      that cause human infections in Switzerland. A difference between clinical
      isolates and strains from pork was also shown by serotyping. Clinical isolates
      frequently belonged to the O3 and O9 groups whereas these two serotypes were not
      found in strains from pork. Resistance to multiple antimicrobial agents was rare.
      When examined by pulsed field gel electrophoresis (PFGE), two strains of fecal
      origin with an identical pattern of resistance to six antimicrobial agents were
      shown to be unrelated. Of four clinical isolates with resistances to five
      antimicrobial agents, two were of the same pulsotype. Retrospectively, it was
      found that these strains came from two members of the same household and thus
      represented a mini-outbreak.

PMID- 17196696
TI  - Inactivation kinetics of selected aerobic and anaerobic bacterial spores by
      pressure-assisted thermal processing.
AB  - The combined pressure-thermal inactivation kinetics of spores from three strains
      of anaerobic (Clostridium sporogenes, C. tyrobutylicum, and Thermoanaerobacterium
      thermosaccharolyticum), and six strains of aerobic (Bacillus amyloliquefaciens
      and B. sphaericus) bacteria were studied. Spores of these bacteria were prepared
      in deionized water and treated in a custom-made kinetic tester over various
      pressure (0.1 and 700 MPa) and thermal (105 and 121 degrees C) combinations.
      Survivor data were modeled using log-linear and Weibull models to obtain relevant
      kinetic parameters. In comparison to thermal treatment alone, the combined
      pressure-thermal conditions accelerated the inactivation of the spores tested. A
      measurable fraction of spore populations was inactivated during the pressure come
      up time. Pressure-assisted thermal processing (PATP) at 700 MPa and 121 degrees C
      for 1 min inactivated up to 7-8 log for some of spores tested. Among bacteria
      evaluated, based on survivor curve data T. thermosaccharolyticum, B.
      amyloliquefaciens Fad 82, and Fad 11/2 were found to produce the most PATP
      resistant spores. PATP inactivation plots showed characteristic upward curvature,
      which is indicative of the tailing behavior. Since both log-linear and Weibull
      kinetic models did not consider microbial reduction during process come-up time,
      our results demonstrated that the estimated model parameters were not adequate to
      compare combined pressure-thermal resistance of various bacterial spores tested.

PMID- 17196697
TI  - Assembled microneedle arrays enhance the transport of compounds varying over a
      large range of molecular weight across human dermatomed skin.
AB  - In this study, we demonstrate the feasibility to use microneedle arrays
      manufactured from commercially available 30G hypodermal needles to enhance the
      transport of compounds up to a molecular weight of 72 kDa. Piercing of human
      dermatomed skin with microneedle arrays was studied by Trypan Blue staining on
      the SC side of the skin and transepidermal water loss measurements (TEWL).
      Passive transport studies were conducted with Cascade Blue (CB, Mw 538), Dextran
      Cascade Blue (DCB, Mw 10 kDa), and FITC coupled Dextran (FITC-Dex, Mw 72 kDa).
      Microneedle arrays with needle lengths of 900, 700 and 550 micro m are able to
      pierce dermatomed human skin as evident from (a) the appearance of blue spots on
      the dermal side of the skin after Trypan Blue treatment and (b) elevated TEWL
      levels after piercing compared to non-treated human dermatomed skin. Microneedles
      with a length of 300 micro m did not pierce human skin in vitro. Transport
      studies performed with model compounds ranging from 538 Da to 72 kDa revealed
      that pretreatment with microneedle arrays enhanced the transport across
      dermatomed human skin. However, some degradation was also observed for FITC-Dex
      and DCB. We conclude that assembled microneedle arrays can be used to deliver
      compounds through the skin up to a molecular weight of at least 72 kDa.

PMID- 17196698
TI  - Heparin conjugated polymeric micelle for long-term delivery of basic fibroblast
      growth factor.
AB  - Heparin conjugated amphiphilic block copolymer, Tetronic-PCL-heparin (TCH), was
      developed and its polymeric micelles (PMs) were prepared as an injectable vehicle
      for long-term delivery of bFGF, which is one of the heparin-binding growth
      factors (HBGF). TCH PMs were fabricated by a single emulsion and solvent
      evaporation method. The structural properties of TCH were confirmed by (1)H NMR,
      FT-IR and GPC. The contents of bound heparin were 0.44 micro g/micro g and the
      heparin activity by APTT assay was 43.6% when compared to free heparin. The
      critical micelle concentration (CMC) of TCH PMs was approximately 0.11 g/l. The
      diameter of TC micelle was approximately 25 nm and its size after conjugation of
      heparin was increased to 114 nm due to the heparin molecules on the shell of the
      micelle. The bFGF loading amount of TCH PMs was considerably higher than that of
      TC, caused by specific interactions between heparin and bFGF. In vitro study,
      bFGF was released from TCH PMs in a controlled manner over 2 months. The results
      demonstrated that TCH PMs become a novel candidate for the long-term delivery of
      various growth factors with heparin-binding domain in tissue engineering.

PMID- 17196699
TI  - Characterization of self-assembling copolymers in aqueous solutions using
      Electron Paramagnetic Resonance and Fluorescence spectroscopy.
AB  - Electron Paramagnetic Resonance and fluorescence spectroscopy have been used to
      determine the micropolarity and microviscosity of self-assembling systems based
      on mmePEG-p(CL-co-TMC) having different PEG chain lengths and different CL/TMC
      ratios and PEG/MOG/SA (45/5/50) polymers with different PEG chain lengths. Four
      reporter probes have been used: two spin probes, 16-doxyl stearic acid and 5
      doxylstearic acid, and two fluorescent probes, pyrene and 1,3-bis(1-pyrenyl)
      propane (P3P). We found that the micelles based on mmePEG-p(CL-co-TMC) polymers
      are of a biphasic nature. The micelles are made of a hydrophilic corona with low
      viscosity while the core of the micelle is more hydrophobic and more viscous. The
      outer shell is made up of PEG chains, the hydrophobic part of the chains making
      the core. The partial hydration of the shell seems to lead to a looser chain
      network than that associated with deeper domains in the micelles. By contrast, in
      micelles composed of PEG/MOG/SA, there is no clear domain separation. This is
      consistent with a spatial configuration of random polymeric chains forming a
      loose network. In these micelles, the microviscosity is low and the
      hydrophobicity is high.

PMID- 17196700
TI  - Sustained virological response to antiviral therapy reduces mortality in HCV
      reinfection after liver transplantation.
AB  - BACKGROUND/AIMS: HCV infection recurs almost in all HCV-positive patients
      receiving liver transplantation and carries a poor prognosis. Aim of this study
      was to analyze efficacy and effect on survival of antiviral therapy in this
      clinical setting. METHODS: Pegylated-interferon alpha-2b and ribavirin were
      administered at a dose of 1 microg/kg of bwt weekly and 600-800 mg/day. Planned
      duration of treatment was 24 or 48 weeks according to HCV genotype. Patients who
      failed to respond at week 24 were considered as non-responders. RESULTS: 61
      patients were enrolled. According to intention-to-treat analysis, 44 (72%)
      patients were considered as treatment failure (31 non-responders, 4 relapsers, 9
      dropout). Sustained virological response was achieved in 17 cases (28%). Genotype
      2, higher doses of antivirals and absence of histological cirrhosis were
      predictors of sustained virological response. In the follow up, patients with
      sustained virological response had a significantly lower mortality compared to
      patients with treatment failure (chi2=6.9; P<0.01). CONCLUSIONS: Response rate to
      antiviral therapy in HCV reinfection after liver transplantation is higher if a
      full dose of antiviral drugs is administered and if treatment starts before
      histological cirrhosis has developed. Sustained virological response improves
      patient survival.

PMID- 17196702
TI  - Impurities in generic pharmaceutical development.
AB  - The current practice of characterization and control of impurities in
      pharmaceuticals is reviewed with emphasis on issues specific to the generic
      industry. Case studies are discussed to demonstrate that generic pharmaceuticals
      are therapeutically equivalent to the branded product, even though the color,
      size, shape, and excipients utilized may not be identical.

PMID- 17196701
TI  - Detection of auto-antibodies against cytochrome P4502E1 (CYP2E1) in chronic
      hepatitis C.
AB  - BACKGROUND/AIMS: Chronic hepatitis C (CHC) is often associated with auto-immune
      reactions. In the light of the role of alcohol in promoting CHC progression, we
      have investigated the possible presence of auto-reactivity against the ethanol
      inducible cytochrome P4502E1 (CYP2E1) in CHC patients with and without alcohol
      consumption. METHODS: The IgG reactivity against recombinant human CYP2E1 was
      evaluated by solid-phase immunoassays in 102 CHC patients with different alcohol
      consumption and 59 HCV-free controls. RESULTS: Auto-antibodies against CYP2E1
      were significantly (p<0.0001) increased in CHC patients as compared to controls.
      Anti-CYP2E1 IgG above the 97th percentile in the controls were evident in 41
      (40%) CHC patients. Competition experiments revealed that CYP2E1 recognition was
      not due to the cross-reactivity with CYP2D6. The detection of anti-CYP2E1 IgG was
      unrelated to alcohol consumption and no difference in gender, age,
      aminotransferase levels and virus genotype was evident among the patients with or
      without anti-CYP2E1 auto-antibodies. However, anti-CYP2E1 auto-reactivity was
      significantly (p=0.025) associated with the severity of periportal/periseptal
      interface hepatitis. Moreover, confocal microscopy demonstrated that anti-CYP2E1
      IgG associated with CHC recognized CYP2E1 exposed on the outer side of hepatocyte
      plasma membranes. CONCLUSIONS: HCV infection favours the breaking of self
      tolerance against CYP2E1 that might contribute to hepatocyte injury.

PMID- 17196703
TI  - Pharmaceutical impurities: regulatory perspective for Abbreviated New Drug
      Applications.
AB  - Impurities in drug substances and drug products have been important regulatory
      issues in the Office of Generic Drugs by having significant impact on the
      approvability of Abbreviated New Drug Application (ANDAs). This review begins
      with a discussion of ANDAs and its similarity/differences with NDAs, highlighting
      the importance of control of pharmaceutical impurities in generic drug product
      development and regulatory assessment. An overview of the FDA draft guidance
      documents "ANDAs: Impurities in Drug Substances" and "ANDAs: Impurities in Drug
      Products" are provided. This introduces the identification and qualification
      procedures for ANDAs and approaches to the establishment of acceptance criteria
      for both drug substance and drug product. Case studies included in this review
      illustrate the proposed pathway for determination of impurities and their
      acceptance criteria, based upon the general principles of these guidances.

PMID- 17196704
TI  - Prognostic significance of RASSF1A promoter methylation on survival of non-small
      cell lung cancer patients treated with gemcitabine.
AB  - The epigenetic inactivation of genes plays an important role in lung cancer. We
      have investigated the methylation status of the promoter region of seven genes
      (APC1A, DAPK, FHIT, p14(ARF), p16(INK4a), RARbeta, RASSF1A) in serum DNA of NSCLC
      patients. The objective of our study was to reveal the influence of such
      alterations on overall survival. Blood samples were drawn pretherapeutically.
      Genomic DNA was purified from serum, treated with sodium bisulfite and
      hypermethylation was detected by a nested methylation-specific PCR in a group of
      92 patients with histologically confirmed stage IIIB and IV NSCLC. All patients
      received gemcitabine first-line alone or in combination with other drugs. The
      vast majority (n=87) showed at least one epigenetic alteration. The methylation
      frequencies of individual genes varied between 25.9 and 47.3%. The
      hypermethylation status of none of the genes had a significant influence on
      median overall survival of the total population. In contrast, patients with a
      methylated RASSF1A gene who showed a partial response survived significantly
      longer (33.6+/-10.4 month) compared to those with a wild-type allele (12.9+/-4.7
      month, P=0.0045). This effect became even more pronounced in combination with
      p14(ARF) (P=0.0004). This difference was not seen in patients with stable or
      progressive disease. A multivariate analysis confirmed that RASSF1A methylation
      was an independent prognostic factor. Our results show that the hypermethylation
      frequency of single genes and the accumulation of epigenetic alterations in
      individual samples of NSCLC patients may vary considerably. Molecular parameters
      such as hypermethylation of RASSF1A or p14(ARF) may be useful prognostic markers
      in subpopulations.

PMID- 17196705
TI  - On sex differences in optimal immunity.
AB  - Sex biases in immunity have generated much interest because of their possible
      connection with sex differences in reproductive strategies. Researchers have
      often argued that males should invest less in immunity than should females. In a
      recent paper, Stoehr and Kokko challenge this reasonably substantiated view of
      'susceptible males'. Their model, and another by Medley, helps highlight relevant
      tests that could explain other important sources of within-species variation in
      immunity and its importance to parasitism.

PMID- 17196706
TI  - Enhanced stability of hydrogen peroxide in the presence of subsurface solids.
AB  - The stabilization of hydrogen peroxide was investigated as a basis for enhancing
      its downgradient transport and contact with contaminants during catalyzed
      H(2)O(2) propagations (CHP) in situ chemical oxidation (ISCO). Stabilization of
      hydrogen peroxide was investigated in slurries containing four characterized
      subsurface solids using phytate, citrate, and malonate as stabilizing agents
      after screening ten potential stabilizers. The extent of hydrogen peroxide
      stabilization and the most effective stabilizer were solid-specific; however,
      phytate was usually the most effective stabilizer, increasing the hydrogen
      peroxide half-life to as much as 50 times. The degree of stabilization was nearly
      as effective at 10 mM concentrations as at 250 mM or 1 M concentrations. The
      effect of stabilization on relative rates of hydroxyl radical activity varied
      between the subsurface solids, but citrate and malonate generally had a greater
      positive effect than phytate. The effect of phytate, citrate, and malonate on the
      relative rates of superoxide generation was minimal to somewhat negative,
      depending on the solid. The results of this research demonstrate that the
      stabilizers phytate, citrate, and malonate can significantly increase the half
      life of hydrogen peroxide in the presence of subsurface solids during CHP
      reactions while maintaining a significant portion of the reactive oxygen species
      activity. Use of these stabilizers in the field will likely improve the delivery
      of hydrogen peroxide and downgradient treatment during CHP ISCO.

PMID- 17196707
TI  - Quantifying uranium complexation by groundwater dissolved organic carbon using
      asymmetrical flow field-flow fractionation.
AB  - The long-term mobility of actinides in groundwaters is important for siting
      nuclear waste facilities and managing waste-rock piles at uranium mines.
      Dissolved organic carbon (DOC) may influence the mobility of uranium, but few
      field-based studies have been undertaken to examine this in typical groundwaters.
      In addition, few techniques are available to isolate DOC and directly quantify
      the metals complexed to it. Determination of U-organic matter association
      constants from analysis of field-collected samples compliments laboratory
      measurements, and these constants are needed for accurate transport calculations.
      The partitioning of U to DOC in a clay-rich aquitard was investigated in 10
      groundwater samples collected between 2 and 30 m depths at one test site. A
      positive correlation was observed between the DOC (4-132 mg/L) and U
      concentrations (20-603 microg/L). The association of U and DOC was examined
      directly using on-line coupling of Asymmetrical Flow Field-Flow Fractionation
      (AsFlFFF) with UV absorbance (UVA) and inductively coupled plasma-mass
      spectrometer (ICP-MS) detectors. This method has the advantages of utilizing very
      small sample volumes (20-50 microL) as well as giving molecular weight
      information on U-organic matter complexes. AsFlFFF-UVA results showed that 47-98%
      of the DOC (4-136 mg C/L) was recovered in the AsFlFFF analysis, of which 25-64%
      occurred in the resolvable peak. This peak corresponded to a weight-average
      molecular weight of about 900-1400 Daltons (Da). In all cases, AsFlFFF-ICP-MS
      suggested that<or=2% of the U, likely present as U(VI), was complexed with the
      DOC. This result was in good agreement with the U speciation modeling performed
      on the sample taken from the 2.3 m depth, which predicted approximately 3% DOC
      complexed U. This good agreement suggests that the AsFlFFF-ICP-MS method may be
      very useful for determining U-organic matter association in small volume samples.
      Because the pH (7.0-8.1) and carbonate concentrations of these waters are typical
      of many groundwaters, these data suggested that facilitated transport of U by DOC
      may be limited in its importance in many groundwater systems.

PMID- 17196708
TI  - NPY signaling through Y1 receptors modulates thalamic oscillations.
AB  - Neuropeptide Y is the ligand of a family of G-protein coupled receptors (Y(1) to
      Y(6)). In the thalamus, exogenous and endogenously released NPY can shorten the
      duration of thalamic oscillations in brain slices from P13 to P15 rats, an in
      vitro model of absence seizures. Here, we examine which Y receptors are involved
      in this modulation. Application of the Y(1) receptor agonist Leu(31)Pro(34)NPY
      caused a reversible reduction in the duration of thalamic oscillations (-26.6+/
      7.8%), while the Y(2) receptor agonist peptideYY((3-36)) and the Y(5) receptor
      agonist BWX-46 did not exert a significant effect. No Y receptor agonist affected
      oscillation period. Application of antagonists of Y(1), Y(2) and Y(5) receptors
      (BIBP3226, BIIE0246 and L152,806, respectively) produced results consistent with
      those obtained from agonists. BIBP3226 caused a reversible disinhibition, an
      effect that increases oscillation duration (18.2+/-9.7%) while BIIE0246 and
      L152,806 had no significant effect. Expression of NPY is limited to neurons in
      the reticular thalamic nucleus (nRt), but Y(1) receptors are expressed in both
      nRt and adjacent thalamic relay nuclei. Thus, intra-nRt or nRt to relay nucleus
      NPY release could cause Y(1) receptor mediated inhibition of thalamic
      oscillations.

PMID- 17196710
TI  - Long-term kainic acid exposure reveals compartmentation of glutamate and
      glutamine metabolism in cultured cerebellar neurons.
AB  - Glutamate neurotoxicity is implicated in most neurodegenerative diseases, and in
      the present study the long-term effects of the glutamate agonist kainic acid (KA)
      on cerebellar neurons are investigated. Primary cell cultures, mainly consisting
      of glutamatergic granule neurons, were cultured in medium containing 0.05 or
      0.50mM KA for 7 days and subsequently incubated in medium containing [U
      13C]glutamate or [U-13C]glutamine. The amount of protein and number of cells were
      greatly reduced in cultures exposed to 0.50 mM KA compared to those exposed to
      0.05 mM KA. Glutamine consumption was not affected by KA concentration, whereas
      that of glutamate was decreased by high KA, confirming reduction in glutamate
      transport reported earlier. Neurons cultured with 0.50 mM KA and incubated with
      glutamate contained decreased amounts of glutamate, aspartate and GABA compared
      to those cultured with 0.05 mM KA. Incubation of cells exposed to 0.50 mM KA with
      glutamine led to an increased amount of glutamate compared to cells exposed to
      0.05 mM KA, whereas the intracellular amounts of aspartate and GABA remained
      unaffected by KA concentration. Furthermore, mitochondrial metabolism of alpha-[U
      13C]ketoglutarate derived from [U-13C]glutamate and [U-13C]glutamine was
      significantly reduced by 0.50 mM KA. The results presented illustrate
      differential vulnerability to KA and can only be understood in terms of inter-
      and intracellular compartmentation.

PMID- 17196709
TI  - Neuropeptide Y: potential role in recurrent developmental seizures.
AB  - Seizures induce profound plastic changes in the brain, including altered
      expression of neuropeptide Y (NPY) and its receptors. Here, I discuss a potential
      role of NPY plasticity in the developmental brain: in a rat model of febrile
      seizures (FS), the most common type of seizures in infants and young children,
      NPY expression was up-regulated in hippocampus after experimentally induced FS.
      Interestingly, NPY up-regulation was associated with an increased seizure
      threshold for additional (recurrent) FS, and this effect was abolished when an
      antagonist against NPY receptor type 2 was applied. These findings suggest that
      inhibitory actions of NPY, released after seizures, exert a protective effect
      that reduces the risk of seizure recurrence in the developing brain.

PMID- 17196711
TI  - Upregulation of dihydropyrimidinase-related protein 2, spectrin alpha II chain,
      heat shock cognate protein 70 pseudogene 1 and tropomodulin 2 after focal
      cerebral ischemia in rats--a proteomics approach.
AB  - In recent years, there are an increasing number of proteomics studies that
      investigated the alterations in the protein expression relevant to human diseases
      but none for stroke. We, therefore, attempted such a study in a paradigm of focal
      cerebral ischemia in rat. Rats were subjected to cerebral ischemia by unilateral
      occlusion of the middle cerebral artery. Global protein analysis was performed
      after 24h on the lesioned and sham-control cerebral cortex using two-dimensional
      gel electrophoresis. Protein spots with more than a 3-fold change in intensity
      were identified by mass spectrometry. Middle cerebral artery occlusion (MCAO)
      caused infarct volume of 18-22% predominantly in the cortex of the lesioned
      hemisphere. Two-dimensional gel electrophoresis resolved about 1500 protein spots
      of which only 12 were significantly upregulated by 3-46-fold. Three spots were
      identified to be dihydropyrimidinase-related protein 2 (DRP-2, also known as
      collapsin response mediator protein 2 (CRMP-2) or turned on after division, 64 kD
      protein (TOAD-64)). The spots varied in pI values only and this may reflect
      different phosphorylation status of the same protein. Two spots were identified
      as spectrin alpha II chain (rat fragment, also known as alpha-fodrin or non
      erythroid alpha chain, SPNA-2); and one spot each for heat shock cognate protein
      70 pseudogene 1 (HSC70-ps1, also known as heat shock protein 8 pseudogene 1), and
      tropomodulin 2 (Tmod2). The upregulation of protein expression was corroborated
      by observed upregulation of mRNA expression. The remaining five spots were not
      identified satisfactorily. As DRP-2, spectrin, and Tmod2 are involved in axonal
      and neurite growth as well as synaptic plasticity and maturation, the presently
      observed upregulation of the expression of these proteins may indicate active
      neuroregeneration and repair at 24h after the induction of cerebral ischemia.

PMID- 17196713
TI  - Tick-borne encephalitis (TBE) vaccination: applying the most suitable vaccination
      schedule.
AB  - Tick-borne encephalitis (TBE) is caused by an arthropod-borne virus, belonging to
      the family of Flaviviridae. In case of disease, which can lead to neurological
      sequelae or even fatal outcomes, only symptomatic treatment is available. TBE can
      be prevented by vaccination. Various primary immunization schedules have been
      developed. To identify the most suitable schedule, the present randomised,
      controlled study was designed to provide data on the immune response elicited by
      four different immunization schedules obtained by ELISA and by neutralization
      test (NT). A total of 398 healthy subjects aged > or =12 years were randomised to
      vaccination according to either the rapid schedule (Group R, vaccination on days
      0, 7 and 21), the conventional schedule (Group C, vaccination on days 0, 28 and
      300), the modified conventional schedule (Group M, vaccination on days 0, 21 and
      300) or the accelerated conventional schedule (Group A, vaccination on days 0, 14
      and 300). Within 3 weeks (i.e. by day 21) antibody levels were higher in Group R
      and Group A than in Group M and Group C. Group R and Group C both had higher
      titres on days 42, 180 and 300, than Group A and Group M. The rapid schedule thus
      combines the advantages of fast protection and of high titres over the
      observation period of 300 days.

PMID- 17196712
TI  - Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in
      AD patients treated with galantamine.
AB  - The relationship between acetylcholinesterase (AChE) activity in the CSF and
      brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD
      patients following galantamine treatment. The first 3 months of the study had a
      randomized double-blind placebo-controlled design, during which 12 patients
      received galantamine (16-24 mg/day) and six patients placebo. This was followed
      by 9 months galantamine treatment in all patients. Activities and protein levels
      of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in
      CSF were assessed in parallel together with the regional brain AChE activity by
      (11)C-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well
      with the in vivo AChE inhibition in the brain. No significant AChE inhibition was
      observed in the placebo group. The increased level of the AChE-R protein was 16%
      higher than that of AChE-S. Both the AChE inhibition and the increased level of
      AChE-R protein positively correlated with the patient's performance in cognitive
      tests associated with visuospatial ability and attention. In conclusion, AChE
      levels in CSF closely mirror in vivo brain AChE levels prior to and after
      treatment with the cholinesterase inhibitors. A positive cognitive response seems
      to dependent on the AChE inhibition level, which is balanced by an increased
      protein level of the AChE-R variant in the patients.

PMID- 17196714
TI  - The prevalence of enduring postnatal perineal morbidity and its relationship to
      perineal trauma.
AB  - OBJECTIVE: to investigate the prevalence of enduring postnatal perineal morbidity
      and its relationship to perineal trauma. DESIGN: a retrospective cross-sectional
      community survey of postnatal women. PARTICIPANTS AND SETTING: a total population
      sample of 2100 women were surveyed from two maternity units within Birmingham.
      Women were identified from the Trust's computerised Maternity Information System
      (MIS). METHODS: Women were surveyed using a self-administered postal
      questionnaire 12 months after birth. The questionnaire included self-assessment
      of perineal pain, perineal healing, urinary incontinence, flatus incontinence,
      faecal incontinence, sexual morbidity and dyspareunia. FINDINGS: a response rate
      of 23.3% was achieved (n=482). A high level of perineal morbidity was reported
      (53.8% stress urinary incontinence, 36.6% urge urinary incontinence, 9.9% liquid
      faecal incontinence, 54.5% with at least one index of sexual morbidity). Women
      with perineal trauma reported significantly more morbidity (sexual morbidity,
      dyspareunia, stress and urge urinary incontinence) than women with an intact
      perineum. Women with perineal trauma also resumed sexual intercourse later than
      women with an intact perineum. Women with a first- or second-degree tear reported
      significantly more perineal morbidity (stress incontinence, sexual morbidity)
      than women with an intact perineum, and resumed sexual intercourse later.
      However, a high percentage of women with an intact perineum also reported new
      onset perineal morbidity: stress urinary incontinence (34.8%); urge urinary
      incontinence (19.5%); flatus incontinence (13.8%); and dyspareunia (25.3%),
      highlighting that enduring perineal morbidity can occur irrespective of perineal
      trauma. CONCLUSION: enduring postnatal perineal morbidity is common in women with
      all types and grades of perineal trauma and intact perineum after childbirth.
      This highlights the need for further debate and research into the prevalence and
      experience of postnatal morbidity.

PMID- 17196715
TI  - The impact and cumulative effects of intimate partner abuse during pregnancy on
      health-related quality of life among Hong Kong Chinese women.
AB  - OBJECTIVE: to explore the prevalence of intimate partner abuse during pregnancy
      and to examine the effect and cumulative effects of different types of intimate
      partner abuse on health-related quality of life. DESIGN: a retrospective, cross
      sectional, comparative design. SETTING: three postnatal wards of a university
      affiliated regional public hospital in Hong Kong. PARTICIPANTS: a community-based
      sample (n=1200) of postnatal women. MEASUREMENTS: the women were identified as
      abused or non-abused using the Abuse Assessment Screen Questionnaire (AAS), and
      various types of abuse were elaborated using the Revised Conflict Tactics Scale
      (CTS-2). The Medical Outcomes Study Short-form 36 Health Survey (SF-36) measured
      the health-related quality of life. FINDINGS: the prevalence rate of intimate
      partner abuse during pregnancy was 134 out of 1200 (11.2%, 95% confidence
      interval [CI] 9.4-13.0%). They consisted of an only psychologically abused group
      (32.1%, 95% CI 24.2-40.0%), an only physically abused group (20.9%, 95% CI 14.0
      27.8%), and a combined psychological and physically abused group (47.0%, 95% CI
      38.5-55.5%). Over half of the women (53.0%, 95% CI 44.5-61.5%) experienced more
      than one type of abuse. Women who had experienced different types of intimate
      partner abuse were associated with lower scores in the majority of domains and
      the subscales of the SF-36 (p<0.05), and there was a cumulative effect of abuse
      on the health-related quality of life of the women. CONCLUSIONS: the problem of
      intimate partner abuse during pregnancy is similar to most Western countries, and
      the negative effect of different types of such abuse on the health-related
      quality of life over time seems to be cumulative. IMPLICATIONS FOR PRACTICE: the
      relatively poor health-related quality of life of the abused women highlights the
      necessity of developing a checklist or a structured questionnaire that will
      assist in the detection of different types and combinations of intimate partner
      abuse, and that will be helpful in the development of more effective preventive
      interventions or programmes.

PMID- 17196716
TI  - A retrospective study of the success, safety and effectiveness of external
      cephalic version without tocolysis in a specialised midwifery centre in the
      Netherlands.
AB  - BACKGROUND: to evaluate the effectiveness of external cephalic version (ECV)
      without tocolysis or epidural analgesia, the complications associated with the
      procedure and the association between the number of ECV attempts and cephalic
      presentation at birth and caesarean section. METHODS: retrospective cohort study
      of all (n=924) ECVs carried out between 1996 and 2000 in a specialised midwifery
      centre in the Netherlands. After bivariate analysis, those variables with a p
      value under 0.05 were considered statistically significant and were tested in a
      logistic regression model using backward stepwise selection. Analyses were
      carried out separately for first ECV attempts and second ECV attempts. FINDINGS:
      in total, 958 ECVs were analysed, 889 first attempts and 69 repeat attempts.
      Seventy per cent of all first ECVs were carried out before 37 weeks, but half of
      those were carried out between 36 and 37 weeks. The success rate for first ECV
      was 41% and for the second ECV 29%. Bivariate analysis showed that the success of
      the first ECV was positively influenced by parity, non-Dutch origin, higher birth
      weight, higher age and longer duration of pregnancy. After logistic regression,
      parity (odds ratio [OR] 2.8, 95% CI 2.1 to 3.7), non-Dutch origin (OR 1.8, 95% CI
      1.2 to 2.8) and birth weight (OR 1.7, 95% CI 1.4 to 2.0) remained factors that
      independently influenced the success of ECV. The odds ratio for duration of
      pregnancy at first ECV was borderline significant: OR 1.2 (1.0 to 1.4). After an
      unsuccessful first ECV, only 13% of the women received a second ECV. The
      prevalence of cephalic presentation at birth increased with 3% after a second
      ECV. Three cases of complications were reported during or very shortly after the
      first ECV, and these did not result in serious complications. No complications
      were reported after a second ECV. CONCLUSION: ECV without tocolysis is a safe
      procedure for pregnant women and their babies. Repeat ECV increases the number of
      cephalic presentations at birth and should be considered after an unsuccessful
      ECV.

PMID- 17196717
TI  - An unusual foreign body in the hand.

PMID- 17196718
TI  - Trigger wrist.
AB  - Trigger wrist is a relatively rare phenomenon. The pathological entities to which
      the term trigger wrist is applied are not well defined in the literature. We
      present three cases of trigger wrist as a result of flexor tendon pathology,
      review the literature and discuss the use of the term "trigger wrist".

PMID- 17196719
TI  - An unusual dorsal fracture-dislocation of the proximal interphalangeal joint.
AB  - A case of dorsal fracture-dislocation of the proximal interphalangeal joint in
      which the volar plate had been pulled from its distal attachment without bony or
      cartilaginous attachments and the lip of the volar plate had also been detached
      separately and was obstructing full flexion of the joint is presented. A
      tentative mechanism of causation of this unusual variant of a common injury is
      suggested.

PMID- 17196720
TI  - Hybrid multidirectional test method to evaluate spinal adjacent-level effects.
AB  - BACKGROUND: Several clinical studies have documented long-term adjacent-level
      effects of spinal fusion, due to stress concentration and motion loss at the
      fused segment. Non-fusion motion preservation devices are designed to eliminate
      or slow down such adverse effects. Therefore, appropriate biomechanical
      evaluation of the adjacent-level effects in spine is important and timely.
      Although many biomechanical studies are available and have provided some
      understanding of the adjacent-level effects, results have large variation and are
      conflicting, mostly due to the use of inappropriate and ill-defined methods. A
      new test method especially designed to study spinal adjacent-level effects is
      needed. METHODS: The proposed Hybrid method uses unconstrained pure moment to
      provide rotation-input for multi-directional testing. The new method has four
      steps: (1) Intact spine specimen with entire mobile region is used. The specimen
      is prepared to measure various biomechanical parameters, e.g., disc pressures,
      ligament strains, and facet loads. (2) Appropriate unconstrained pure moment is
      applied to the intact specimen and total range of motion is determined. (3)
      Unconstrained pure moment is applied to the spinal construct (specimen with an
      implant) until the total range of motion of the construct equals that of the
      intact. (4) Statistical comparison of the biomechanical parameters between the
      construct and intact quantifies the adjacent-level effects. FINDINGS: The
      uniqueness of the proposed method, to study the adjacent level effects due to
      fusion and non-fusion devices, is that it applies the needed rotation-input to
      the spine specimen, using available methodology with minimal modification.
      INTERPRETATION: Previous studies have lacked appropriate and well-defined
      methodologies to evaluate spinal adjacent-level effects. The proposed method uses
      well-known methodology and yields high quality, and laboratory-independent
      results for the fusion and non-fusion devices.

PMID- 17196721
TI  - The three-dimensional motions of glenohumeral joint under semi-loaded condition
      during arm abduction using vertically open MRI.
AB  - BACKGROUND: Magnetic resonance imaging is an accurate non-invasive tool for
      visualizing muscles, tendons, and bones. It also provides 3D coordinate values.
      The purpose of the present study was to visualize and quantify the 3D positions
      of the glenohumeral joint during isometric abduction of the arm using vertically
      open magnetic resonance imaging. METHODS: We examined 14 shoulders of seven
      healthy volunteers. Magnetic resonance images were obtained in a seated position
      and in seven static positions of the arm from 0 degrees to maximum abduction
      using vertically open magnetic resonance imaging. 3D surface models were created
      and 3D movements of each bone in the glenohumeral joint were calculated using a
      computer algorithm. We analyzed the translation and contact pattern of the
      glenohumeral joint. FINDINGS: In supero-inferior direction, the humeral head
      translated slight inferiorly from +1.9 (SD 1.0) mm at 0 degrees to +0.8 (SD 1.8)
      mm at the maximum abduction. In antero-posterior direction, the humeral head
      translated anteriorly from 0 degrees to 90 degrees (mean +2.4, SD 2.6 mm) and
      posteriorly from 90 degrees to 150 degrees of abduction (mean -1.4, SD 2.7 mm).
      Furthermore, the humeral head had a unique contact patterns with the glenoid; the
      contact part of the humeral head with the glenoid changed from the central part
      to the posterior in the midrange of abduction. INTERPRETATION: The humeral head
      showed a small translation in the antero-posterior direction between 90 degrees
      and 150 degrees of abduction. In addition, the posterior part of the humeral head
      contacted the glenoid in this range of abduction. These findings of motion
      patterns in asymptomatic subjects will be necessary when comparing the kinematics
      with pathologic condition such as the glenohumeral instability and rotator cuff
      tear.

PMID- 17196723
TI  - Linked versus unlinked estimates of mortality and length of life by education and
      marital status: evidence from the first record linkage study in Lithuania.
AB  - Earlier studies have found large and increasing with time differences in
      mortality by education and marital status in post-Soviet countries. Their results
      are based on independent tabulations of population and deaths counts (unlinked
      data). The present study provides the first census-linked estimates of group
      specific mortality and the first comparison between census-linked and unlinked
      mortality estimates for a post-Soviet country. The study is based on a data set
      linking 140,000 deaths occurring in 2001-2004 in Lithuania with the population
      census of 2001. The same socio-demographic information about the deceased is
      available from both the census and death records. Cross-tabulations and Poisson
      regressions are used to compare linked and unlinked data. Linked and unlinked
      estimates of life expectancies and mortality rate ratios are calculated with
      standard life table techniques and Poisson regressions. For the two socio
      demographic variables under study, the values from the death records partly
      differ from those from the census records. The deviations are especially
      significant for education, with 72-73%, 66-67%, and 82-84% matching for higher
      education, secondary education, and lower education, respectively. For marital
      status, deviations are less frequent. For education and marital status, unlinked
      estimates tend to overstate mortality in disadvantaged groups and they understate
      mortality in advantaged groups. The differences in inter-group life expectancy
      and the mortality rate ratios thus are significantly overestimated in the
      unlinked data. Socio-demographic differences in mortality previously observed in
      Lithuania and possibly other post-Soviet countries are overestimated. The growth
      in inequalities over the 1990s is real but might be overstated. The results of
      this study confirm the existence of large and widening health inequalities but
      call for better data.

PMID- 17196724
TI  - Quantifying the urban environment: a scale measure of urbanicity outperforms the
      urban-rural dichotomy.
AB  - The rapid urbanization of the developing world has important consequences for
      human health. Although several authorities have called for better research on the
      relationships between urbanicity and health, most researchers still use a poor
      measurement of urbanicity, the urban-rural dichotomy. Our goal was to construct a
      scale of urbanicity using community level data from the Cebu Longitudinal Health
      and Nutrition Survey. We used established scale development methods to validate
      the new measure and tested its performance against the dichotomy. The new scale
      illustrated misclassification by the urban-rural dichotomy, and was able to
      detect differences in urbanicity, both between communities and across time, that
      were not apparent before. Furthermore, using a continuous measure of urbanicity
      allowed for better illustrations of the relationships between urbanicity and
      health. The new scale is a better measure of urbanicity than the traditionally
      used urban-rural dichotomy.

PMID- 17196725
TI  - Development of tardive dyskinesia in a patient taking amisulpride.

PMID- 17196726
TI  - Simvastatin attenuates cisplatin-induced kidney and liver damage in rats.
AB  - Statins have anti-inflammatory effects that are not directly related to their
      cholesterol-lowering activity. This study aimed to investigate the effect of
      simvastatin on the extent of tissue damage in cisplatin-induced nephrotoxicity
      and hepatotoxicity. The rats received a single intravenous injection of 2.5mgkg(
      1) cisplatin. Other groups received either simvastatin (1mgkg(-1)) or the vehicle
      (ethanol:saline) intraperitoneally for 10 days beginning 5 days prior to
      cisplatin injection. All animals were decapitated 5 days after cisplatin
      administration. Trunk blood was collected and analyzed for blood urea nitrogen
      (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), lactate dehydrogenase (LDH), albumin, and total bilirubin levels. The
      urine samples were used for the calculation of creatinine clearance levels. The
      kidney and liver samples were stored for the measurement of malondialdehyde (MDA)
      and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content
      or were processed for histopathological examinations. Formation of reactive
      oxygen species in tissue samples was monitored by using chemiluminescence method.
      Simvastation reduced the extent of both kidney and liver damage and preserved
      both kidney and liver functions (p<0.01-0.001). Increase in liver MDA level with
      a concomitant reduction in GSH in the cisplatin group was attenuated by
      simvastatin treatment (p<0.05-0.01). Increase in tissue collagen content and
      chemiluminescence levels in the kidney and liver samples of the cisplatin group
      was also reversed by simvastatin (p<0.001). In conclusion, simvastatin is
      beneficial in cisplatin-induced kidney and liver dysfunction and organ damage in
      rats via prevention of lipid peroxidation and tissue fibrosis, preservation of
      antioxidant glutathione, and suppression of neutrophil infiltration.

PMID- 17196727
TI  - Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles:
      differential responses related to surface properties.
AB  - Surface properties are critical to assess effects of ultrafine-TiO(2) particles.
      The aim of this study was to assess lung toxicity in rats of newly developed,
      well characterized, ultrafine-TiO(2) particles and compare them to TiO(2) samples
      in two different size ranges and surface modifications. Groups of rats were
      intratracheally instilled with doses of 1 or 5mg/kg of either two ultrafine
      rutile TiO(2) particles (uf-1 or uf-2); rutile R-100 fine-TiO(2) (F-1); 80/20
      anatase/rutile P25 ultrafine-TiO(2) (uf-3); or alpha-quartz particles. Phosphate
      buffered saline (PBS) solution instilled rats served as vehicle controls.
      Following exposures, the lungs of PBS and particle-exposed rats were evaluated
      for bronchoalveolar lavage (BAL) fluid inflammatory markers, cell proliferation,
      and by histopathology at post-instillation time points of 24h, 1 week, 1 and 3
      months. The ranking of lung inflammation/cytotoxicity/cell proliferation and
      histopathological responses was quartz>uf-3>F-1=uf-1=uf-2. Exposures to quartz
      and to a lesser degree, uf-3 anatase/rutile TiO(2) particles produced pulmonary
      inflammation, cytotoxicity and adverse lung tissue effects. In contrast,
      exposures to F-1 fine-TiO(2) particles or to uf-1/uf-2 ultrafine-TiO(2) particle
      types produced transient inflammation. We conclude that differences in responses
      to anatase/rutile uf-3 TiO(2) particles versus the rutile uf-1 and uf-2 TiO(2)
      particles could be related to crystal structure, inherent pH of the particles, or
      surface chemical reactivity. Thus, based on these results, inhaled rutile
      ultrafine-TiO(2) particles are expected to have a low risk potential for
      producing adverse pulmonary health effects. Finally, the results demonstrate that
      exposures to ultrafine-TiO(2) particle-types can produce differential pulmonary
      effects, based upon their composition, and crystal structure. Thus, the lung
      toxicity of anatase/rutile uf-3 should not be viewed as representative for all
      ultrafine-TiO(2) particle-types.

PMID- 17196728
TI  - The effect of plant phenols on the expression and activity of phorbol ester
      induced PKC in mouse epidermis.
AB  - Protein kinase C (PKC) is thought to be a major intracellular receptor for the
      mouse skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The
      diversity of PKC isoforms, and their central role in many signaling pathways,
      makes them important targets for potential chemopreventive agents. Our earlier
      studies showed that the plant phenols protocatechuic acid, chlorogenic acid and
      tannic acid alter the activity of enzymes involved in carcinogen activation,
      inhibit the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in
      mouse epidermis and decrease the level of lipid peroxidation in the epidermal
      microsomes. In the present study the effects of protocatechuic acid, chlorogenic
      acid and tannic acid on TPA-stimulated PKC isozymes alpha, beta(1), beta(2),
      gamma and zeta activity, and their distribution in mouse epidermis, was examined.
      The application of these phenolics 15 min before a single dose (3.4 nmol) of TPA
      resulted in significant inhibition of PKC translocation and a subsequent decrease
      in classical and novel/atypical PKC isoforms in comparison to a group of mice
      treated with TPA alone. The most potent inhibitor of PKC translocation and
      activity was tannic acid. This compound increased the levels of PKCalpha,
      beta(1), beta(2) in the cytosolic fraction by between 127% and 492% in comparison
      with TPA treated group of mice. Tannic acid decreased the activities of all three
      PKC classes by approximately 94% in the membrane fraction in comparison with the
      TPA treated group of animals. The effect of protocatechuic and chlorogenic acids
      on the distribution and activity of PKC isozymes was moderate. These compounds
      mostly affected translocation of PKCalpha and subsequently the activity of
      classical PKC. The enzyme activity in the particulate fraction was reduced by 59%
      and 43% in comparison with the TPA group, respectively. Thus, the results of
      these studies suggest that the subcellular distribution of PKC isoforms, and the
      activity of PKCs, can be modulated by plant phenolic acids, particularly tannic
      acid, and that such actions represent a part of the anti-promotional activity of
      these substances in mouse epidermis.

PMID- 17196729
TI  - Use of short fiber-reinforced composite with semi-interpenetrating polymer
      network matrix in fixed partial dentures.
AB  - OBJECTIVES: The aim of this study was to determine the static load-bearing
      capacity of fixed partial dentures (FPDs) made of experimental composite resin
      (FC) with short fiber fillers and interpenetrating polymer network (IPN) polymer
      matrix. MATERIALS AND METHODS: Experimental composite FC resin was prepared by
      mixing short E-glass fibers (3mm in length) of 22.5wt% and IPN-resin 22.5wt% with
      silane treated silica fillers 55wt%. Four groups of FPDs (3-unit) were fabricated
      (n=6); Group A: made from commercial composite resin (Sinfony dentin, 3M-ESPE,
      control), Group B: Sinfony and fiber-reinforced composite (FRC) substructure,
      Group C: made from FC, Group D: made from FC with 1mm surface layer of Sinfony.
      The bridges were polymerized with a hand-light curing unit for 40s then post
      cured in vacuum curing device (Visio Beta) for 15min before they were statically
      loaded with speed of 1mm/min until fracture. Failure modes were visually
      examined. Data were analyzed using ANOVA (p=0.05). RESULTS: ANOVA revealed that
      bridges made from experimental fiber composite had statistically significantly
      higher load-bearing capacity (2171N) (p<0.05) than the control restorations
      (1482N). SIGNIFICANCE: Restorations made from short glass fiber containing
      composite resin with IPN-polymer matrix showed better load bearing capacity than
      in those made with conventional composites resin and similar with those
      reinforced with FRC-substructure.

PMID- 17196730
TI  - The effects of load and toothpaste on powered toothbrush vibrations.
AB  - OBJECTIVES: The primary cleaning action of powered toothbrushes is the motion of
      the bristles in contact with the tooth surfaces. The aim of this study was to use
      scanning laser vibrometry to determine the effects of load and toothpaste on the
      bristle vibration characteristics of four powered toothbrushes (Oral-B Sonic
      Complete; Oral-B Professional Care 8000 Series; Sonicare Elite and Ultrasonex).
      METHODS: Toothbrushes were initially scanned, with the laser vibrometer, under
      unloaded conditions to provide baseline readings. Toothbrushes were then assessed
      under loaded conditions (1.00 N and 2.00 N), with and without toothpaste, to
      observe the effect on bristle motion. RESULTS: Application of 1.00 N load
      significantly reduced the displacement amplitudes of all powered toothbrushes
      (p<0.003) except for the Sonicare (p>0.497). With toothpaste, 1.00 N load caused
      a significant decrease in vibration displacement amplitude for all brushes
      (p<0.0001). The application of 2.00 N, with and without toothpaste, significantly
      reduced all toothbrushes vibration displacement amplitude (p<0.0001). Under all
      investigation conditions, the Oral-B 8000 had the largest vibration displacement
      amplitude of the toothbrushes tested. CONCLUSIONS: Load and toothpaste
      significantly affected the performance of powered toothbrushes. Understanding why
      these factors affect certain toothbrush designs more than others may lead to
      toothbrushes being designed with greater clinical efficacy.

PMID- 17196731
TI  - Radial glial origin of the adult neural stem cells in the subventricular zone.
AB  - Adult neurogenesis persists within restricted areas of the mammalian brain,
      giving rise prevalently to neuronal precursors that integrate inside the
      hippocampus and olfactory bulb. The source of this continuous cell production
      consists of neural stem cells which have been identified as elements of the
      astroglial lineage. This counterintuitive finding overlaps with the recent
      discovery that embryonic radial glia can themselves act as stem cells, capable of
      producing both neurons and glia during development. Although radial glia was
      thought to disappear early postnatally at the end of neurogenesis by
      transformation into parenchymal astrocytes, it has recently been demonstrated
      that some radial glial cells somehow persist within the adult forebrain
      subventricular zone, hidden among astrocytes of the glial tubes. This
      transformation occurs in parallel with overall morphological and molecular
      changes within the neurogenic site, whose specific steps, mechanisms, and
      outcomes are not yet fully understood. The modified radial glia appear to be
      neural progenitor cells belonging to the astroglial lineage (type B cells)
      assuring both stem cell self-renewal and production of a differentiated progeny
      in the adult subventricular zone, and also playing regulatory roles in stem cell
      niche maintenance.

PMID- 17196732
TI  - Error-processing deficits in patients with cocaine dependence.
AB  - Cocaine abuse and addiction can be characterized by a persisting use of cocaine
      in the face of adverse consequences. In the present study we focus on one
      specific element of adverse consequences: the making of errors. The aim of this
      study was to determine whether cocaine-dependent persons have error-processing
      deficits as measured using error-related negativity (ERN) and error positivity
      (Pe). Event-related potentials (ERPs) during an Eriksen flanker task were
      recorded from cocaine-dependent patients and a control group. Cocaine-addicted
      patients showed reduced ERN and Pe components as compared to a control group. On
      the behavioral level, patients showed reduced post-error accuracy improvement.
      The present findings reveal that cocaine addiction is associated with reduced
      error processing and impaired behavioral correction of errors after an error is
      made. These deficits may be associated with a compromised dopamine system. It is
      argued that these cognitive deficits may contribute to the maintenance of the
      cocaine addiction.

PMID- 17196733
TI  - Symptoms of depression and cardiovascular reactions to acute psychological
      stress: evidence from a population study.
AB  - Depression and exaggerated cardiovascular reactivity are considered risk factors
      for cardiovascular disease, possibly as a result of common antecedents, such as
      altered autonomic nervous system function. We examined the association between
      depressive symptomatology and cardiovascular reactions to psychological stress in
      1608 adults (875 women) comprising 3 distinct age cohorts: 24-, 44-, and 63-year
      olds. Depression was assessed using the Hospital Anxiety and Depression Scale.
      Blood pressure and heart rate were measured at baseline and during the paced
      auditory serial arithmetic test. Depression scores were negatively associated
      with systolic blood pressure and heart rate reactions, after adjustment for
      likely confounders such as sex, cohort, occupational status, body mass index,
      stress task performance score, baseline cardiovascular activity, antidepressant,
      and antihypertensive medication. The direction of association was opposite to
      that which would be expected if excessive reactivity were to mediate the
      association between depression and cardiovascular disease outcomes or if they
      shared common antecedents.

PMID- 17196735
TI  - Obstetricians and counseling on breastfeeding on prenatal consultations.

PMID- 17196736
TI  - Intestinal metastases from cervical carcinoma may be falsely attributed to
      radiation enteropathy.

PMID- 17196737
TI  - Open radical retropubic prostatectomy.
AB  - We describe a surgical procedure for radical retropubic prostatectomies that we
      have used in a prospective series of 231 patients with localised prostate cancer
      (mean age 63 yr; range: 46-75 yr). Nerve-sparing was performed in 148 of 231
      patients. We insist on three points: (1) high-quality preservation of the
      sphincter, with the sphincter divided to keep its anatomic environment intact;
      (2) high-precision retrograde dissection of the neurovascular bundles in the mid
      gland prostate zone for early recovery of erectile function (the dissection of
      the bundles is described for each prostate zone [apex, mid-gland, base]); and (3)
      the need to standardise each step of the procedure for a reproducible protocol
      independent of individual patient anatomy. These three measures will ensure the
      best cancer control with the best functional results. The rate of positive
      margins for patients with organ-confined (pT2) cancer was 3.7% (2.4% related to
      an invaded striated sphincter). The quality of the excised specimens was further
      checked by noting the frequency of capsular incision (2.6%) and of inked benign
      prostatic glands (2.6%). By 12 mo, 94% of patients were fully continent and 70.5%
      had recovered the ability to maintain an erection for satisfactory sexual
      intercourse without the need for medication.

PMID- 17196739
TI  - Increased expression of DNA methyltransferase 1 (DNMT1) protein in uterine cervix
      squamous cell carcinoma and its precursor lesion.
AB  - Aberrant DNA methylation has been shown to play important roles during multistage
      carcinogenesis in various human organs. The aim of this study was to evaluate the
      significance of DNA methyltransferase 1 (DNMT1) protein expression during
      cervical carcinogenesis. We carried out an immunohistochemical examination for
      DNMT1 in 34 samples of histologically normal squamous epithelium, 36 samples of
      low-grade cervical intraepithelial neoplasia (CIN), 61 samples of higher-grade
      CIN and 30 samples of squamous cell carcinoma of the uterine cervix. The DNMT1
      protein expression score, reflecting the intensity and incidence of DNMT1 nuclear
      immunoreactivity, was increased even in low-grade CIN (P<0.0001) in comparison
      with histologically normal squamous epithelium and was further increased in
      higher-grade CIN (P<0.0001 compared to low-grade CIN). The DNMT1 protein
      expression score remained at a plateau in microinvasive carcinoma (Stage IA,
      P=0.0690 compared to higher-grade CIN) and then decreased with cancer invasion
      (Stage IB or more, P=0.0176 compared to Stage IA), whereas the proliferating cell
      nuclear antigen (PCNA) labeling index did not decrease with cancer invasion
      (P=0.8259 between Stage IA and Stage IB or more). Thus, the DNMT1 protein
      expression score and the PCNA labeling index were not mutually correlated in
      squamous cell carcinoma of the uterine cervix (P=0.2304). These data suggest that
      progressively increasing expression of DNMT1 protein is not entirely a secondary
      result of increased cell proliferative activity, but is associated with an early
      step of multistage cervical carcinogenesis.

PMID- 17196740
TI  - Electrochemical-assisted photodegradation of mixed dye and textile effluents
      using TiO2 thin films.
AB  - Mixed dye consists of six commercial dyes and textile effluents from cotton
      dyeing process were treated by electrochemical-assisted photodegradation under
      halogen lamp illumination. Two types of effluents were collected which are
      samples before and after undergone pre-treatment at the factory wastewater
      treatment plant. The photodegradation process was studied by evaluating the
      changes in concentration employing UV-vis spectrophotometer (UV-vis) and total
      organic carbon (TOC) analysis. The photoelectrochemical degradation of mixed dye
      was found to follow the Langmuir Hinshelwood pseudo-first order kinetic while
      pseudo-second order kinetic model for effluents by using TOC analyses. The
      chemical oxygen demand (COD) and biochemical oxygen demand (BOD) values of mixed
      dye and raw effluents were reported. Photoelectrochemical characteristic of
      pollutants was studied using the cyclic voltammetry technique. Raw effluent was
      found to exhibit stronger reduction behaviour at cathodic bias potential but
      slightly less photoresponse at anodic bias than mixed dye.

PMID- 17196741
TI  - Separation/preconcentration of silver(I) and lead(II) in environmental samples on
      cellulose nitrate membrane filter prior to their flame atomic absorption
      spectrometric determinations.
AB  - An enrichment method for trace amounts of Ag(I) and Pb(II) has been established
      prior to their flame atomic absorption spectrometric determinations. The
      preconcentration/separation procedure is based on chelate formation of Ag(I) and
      Pb(II) with ammonium pyrrolidine dithiocarbamate (APDC) and on retention of the
      chelates on cellulose nitrate membrane filter. The influences of some analytical
      parameters including pH and amounts of reagent, etc. on the recoveries of
      analytes were investigated. The effects of interferic ions on the quantitative
      recoveries of analytes were also examined. The detection limits (k=3, N=11) were
      4.6 microg L(-1) for silver(I) and 15.3 microg L(-1) for lead(II). The relative
      standard deviations (R.S.D.) of the determinations for analyte ions were below
      3%. The method was applied to environmental samples for the determination of
      analyte ions with satisfactory results (recoveries>95%).

PMID- 17196738
TI  - Steroidogenic factor-1 is a sphingolipid binding protein.
AB  - Steroidogenic factor (SF1, NR5A1, Ad4BP) is an orphan nuclear receptor that is
      essential for steroid hormone-biosynthesis and endocrine development. Studies
      have found that the ability of this receptor to increase target gene expression
      can be regulated by post-translational modification, subnuclear localization, and
      protein-protein interactions. Recent crystallographic studies and our mass
      spectrometric analyses of the endogenous receptor have demonstrated an integral
      role for ligand-binding in the control of SF1 transactivation activity. Herein,
      we discuss our findings that sphingosine is an endogenous ligand for SF1. These
      studies and the structural findings of others have demonstrated that the receptor
      can bind both sphingolipids and phospholipids. Thus, it is likely that multiple
      bioactive lipids are ligands for SF1 and that these lipids will differentially
      act to control SF1 activity in a context-dependent manner. Finally, these
      findings highlight a central role for bioactive lipids as mediators of trophic
      hormone-stimulated steroid hormone biosynthesis.

PMID- 17196742
TI  - A sub-second fast Fourier transform-adsorptive voltammetric technique for the
      nano-level determination of guthion at a gold microelectrode in flowing
      solutions.
AB  - This research demonstrates the quick guthion monitoring with the help of a
      sensitive method called fast Fourier transformation continuous cyclic voltammetry
      (FFTCV). Fortunately, FFTCV illustrates the benefits of precision, determination
      speed, cost-effectiveness, accuracy and simplicity, in comparison with formerly
      reported techniques. In particular, this method was applied to a gold
      microelectrode in flowing solutions to detect the guthion concentration in its
      formulations. The effects of several parameters were examined regarding the
      sensitivity of the method. After a series of experiments, the detection limit of
      the method was found to be equal to 1.27 pg/mL, when the optimum conditions were
      imposed, which is a scan rate value of 40V/s, an accumulation time of 0.4s, an
      accumulation potential of 0mV and a pH value of 2. During the measurements
      performance, the integration range of currents included all the potential scan
      ranges, even the oxidation and reduction of the Au surface electrode, for the
      achievement of a sensitive determination. Then, the potential waveform,
      consisting of the potential steps for cleaning, accumulation and the step for the
      potential ramp, was applied to an Au disk microelectrode in a continuous way. It
      is also important to refer to the positive points, presented only by the use of
      this technique. Firstly, it is no longer necessary to remove the oxygen from the
      test solution. Furthermore, the quick determination of any such compound in many
      chromatographic methods is possible. Thirdly, the corresponding detection limit
      is of nanomolar level.

PMID- 17196743
TI  - Association analysis of the dopamine receptor D2 (DRD2) SNP rs1076560 in
      alcoholic patients.
AB  - The dopamine system plays a well-established role in alcoholism. In this study,
      we examined the association between the single-nucleotide polymorphism (SNP)
      rs1076560 of the dopamine receptor D2 (DRD2) gene and susceptibility to
      alcoholism. SNP rs1076560 (C/A) is located in intron 6 of DRD2, where it is 1.4
      kb downstream from alternative exon 6 and 83 bp upstream from exon 7. A total of
      248 alcoholic patients and 322 healthy controls, all Japanese males, were
      genotyped for rs1076560 polymorphism by direct sequencing and allele-specific
      PCR. Data were analyzed using standard chi(2) statistics and a backwards logistic
      regression approach to adjust for the contribution of aldehyde dehydrogenase-2
      (ALDH2) genotype status. The DRD2 risk allele A was more prevalent in the
      alcoholic patients (40.1%) than in the healthy controls (34.0%) (P=0.034, odds
      ratio=1.300, 95% confidence interval=1.020-1.657). These data identify SNP
      rs1076560 as a potentially important variable in the development of alcoholism.

PMID- 17196744
TI  - Neuroprotective effect of carnosine on necrotic cell death in PC12 cells.
AB  - The nervous tissue of many vertebrates, including humans, can synthesize beta
      alanyl-L-histidine (carnosine). The biological functions of carnosine are still
      open to question, although several theories supported by strong experimental data
      have been proposed. The objective of this study was to examine the effects of
      carnosine on neurotoxicity in differentiated rat pheochromocytoma (PC12) cells.
      Neurotoxicity was induced by N-methyl-D-aspartate (NMDA), which caused time- and
      concentration-dependent cell death as measured by MTT and LDH assays.
      Pretreatment with carnosine significantly prevented the neurotoxicity in a
      concentration-dependent manner. The protective effect of carnosine was
      antagonized by the H1 receptor antagonist pyrilamine, but not by the H2 receptor
      antagonist cimetidine. In addition, alpha-fluoromethylhistidine, a histidine
      decarboxylase inhibitor, slightly reversed the protective action of carnosine.
      These results indicate that carnosine can effectively protect against NMDA
      induced necrosis in PC12 cells, and its protection may in part be due to the
      activation of the postsynaptic histamine H1 receptor. The study suggests that
      carnosine may be an endogenous protective factor and calls for its further study
      as a new anti-excitotoxic agent.

PMID- 17196745
TI  - Frontal anatomy and reaction time in Autism.
AB  - Widespread frontal lobe abnormalities, encompassing anatomy and function, are
      known to be implicated in Autistic Spectrum Disorders (ASD). The correlation
      between neurobiology and behaviour, however, is poorly understood in ASD. The aim
      of this study was to investigate frontal lobe anatomy and cognitive function in
      individuals with ASD, compared to control subjects. Thus, we assessed whole brain
      and frontal lobe parenchymal volume, and grey and white matter density
      differences in ASD, compared to control subjects, using high resolution T1
      weighted magnetic resonance imaging (MRI). Furthermore, all subjects underwent a
      computerized reaction time task (RTT) for cognitive assessment. No differences in
      total parenchymal brain volume were observed, however, autistic individuals
      showed significantly smaller frontal lobe parenchymal volume (FLPV) and decreased
      white matter density, compared to control subjects. Error rates did not differ
      significantly between groups during the RTT, but ASD individuals responded
      significantly slower to target stimuli. Furthermore, reduced FLPV correlated
      positively with increased reaction time in individual with ASD. Decreased FLPV
      could be an indicator for abnormal brain development resulting in reduced
      processing speed in ASD.

PMID- 17196746
TI  - Spatio-temporal expression of cysteinyl leukotriene receptor-2 mRNA in rat brain
      after focal cerebral ischemia.
AB  - Cysteinyl leukotrienes (CysLTs) induce inflammatory responses mediated by
      activating CysLT(1) and CysLT(2) receptors. We have recently reported that
      CysLT(1) receptor expression is increased in rat brain after focal cerebral
      ischemia and the increased expression is spatio-temporally related to acute
      neuronal injury and late astrocyte proliferation. Here we report spatio-temporal
      expression of CysLT(2) receptor mRNA in rat brain after focal cerebral ischemia
      induced by 30min of middle cerebral artery occlusion. We found that the neuron
      density was gradually decreased or disappeared in the ischemic core and boundary
      zone during 14 days after reperfusion, and the astrocyte population in the
      boundary zone was increased 3-14 days after reperfusion. In the ischemic core,
      the expression of CysLT(2) receptor mRNA was increased at 6, 12 and 24h and then
      recovered at 3, 7 and 14 days after reperfusion. In the boundary zone, the
      expression was significantly increased 3, 7 and 14 days after reperfusion. The
      results suggest that CysLT(2) receptor may be related to the acute neuronal
      injury and late astrocyte proliferation in the ischemic brain.

PMID- 17196748
TI  - Binding properties of Clostridium botulinum type C progenitor toxin to mucins.
AB  - It has been reported that Clostridium botulinum type C 16S progenitor toxin (C16S
      toxin) first binds to the sialic acid on the cell surface of mucin before
      invading cells [A. Nishikawa, N. Uotsu, H. Arimitsu, J.C. Lee, Y. Miura, Y.
      Fujinaga, H. Nakada, T. Watanabe, T. Ohyama, Y. Sakano, K. Oguma, The receptor
      and transporter for internalization of Clostridium botulinum type C progenitor
      toxin into HT-29 cells, Biochem. Biophys. Res. Commun. 319 (2004) 327-333]. In
      this study we investigated the binding properties of the C16S toxin to
      glycoproteins. Although the toxin bound to membrane blotted mucin derived from
      the bovine submaxillary gland (BSM), which contains a lot of sialyl
      oligosaccharides, it did not bind to neuraminidase-treated BSM. The binding of
      the toxin to BSM was inhibited by N-acetylneuraminic acid, N-glycolylneuraminic
      acid, and sialyl oligosaccharides strongly, but was not inhibited by neutral
      oligosaccharides. Both sialyl alpha2-3 lactose and sialyl alpha2-6 lactose
      prevented binding similarly. On the other hand, the toxin also bound well to
      porcine gastric mucin. In this case, neutral oligosaccharides might play an
      important role as ligand, since galactose and lactose inhibited binding. These
      results suggest that the toxin is capable of recognizing a wide variety of
      oligosaccharide structures.

PMID- 17196749
TI  - Systemic therapy in metastatic or recurrent endometrial cancer.
AB  - Endometrial cancer is one of the most common gynecologic malignancies. In
      patients with advanced or recurrent endometrial cancer survival is greatly
      diminished. Hormonal therapy and chemotherapy play a major role in the management
      of advanced or recurrent endometrial cancer. Endocrine therapy provides a 10-20%
      response rate (RR) and survival of less than 1 year. Combination chemotherapy
      offers a RR of 40-60%, but the survival is still less than 1 year. The
      combination of cisplatin plus doxorubicin is the most commonly used regimen, but
      carboplatin plus paclitaxel represents an efficacious, low toxicity regimen in
      advanced or recurrent endometrial cancer. The addition of paclitaxel to cisplatin
      plus doxorubicin appears to improve response rates, progression-free survival and
      overall survival, but to worsen toxicity profile. At this time the focus of
      future research should be on the use of novel targeted agents, since it is
      unlikely that further significant advances could be made with chemotherapy and
      endocrine therapy. mTOR inhibitors represent a promising therapeutic strategy for
      endometrial cancer. Anti-HER-2/neu targeted therapy might be a novel and
      attractive therapeutic option in patients with biologically aggressive variants
      (uterine serous papillary carcinoma, clear cell carcinoma) of endometrial cancer.
      Research in better understanding the signal transduction pathways in endometrial
      carcinogenesis will allow the development of specific and selective molecularly
      targeted inhibitors.

PMID- 17196747
TI  - p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the
      parkinsonian brain.
AB  - We and other workers found markedly increased levels of proinflammatory cytokines
      and apoptosis-related proteins in parkinsonian brain. Although the pathogenesis
      of Parkinson's disease (PD) remains enigmatic, apoptosis might be involved in the
      degeneration of dopaminergic neurons in PD. To investigate the possible presence
      of other inflammatory cytokines and/or apoptosis-related protein, the levels of
      p53 protein, interferon-gamma, and NF-kappaB were measured for the first time in
      the brain (substantia nigra, caudate nucleus, putamen, cerebellum, and frontal
      cortex) from control and parkinsonian patients by a highly sensitive sandwich
      enzyme-linked immunosorbent assay. The p53 protein level in the caudate nucleus
      was significantly higher in parkinsonian patients than in controls (P<0.05),
      whereas this protein in the substantia nigra, putamen, and cerebral cortex showed
      no significant difference between parkinsonian and control subjects. The
      interferon-gamma level was significantly higher in the nigrostriatal dopaminergic
      regions (substantia nigra, caudate nucleus, and putamen) in parkinsonian patients
      than in the controls (P<0.05), but was not significantly different in the
      cerebellum or frontal cortex between the two groups. In accordance with previous
      immunohistochemical analysis, the NF-kappaB level in the nigrostriatal
      dopaminergic regions was significantly higher in parkinsonian patients than in
      the controls (P<0.05). These data suggest that the significant increase in the
      levels of p53 protein, interferon-gamma, and NF-kappaB reflect apoptosis and the
      inflammatory state in the parkinsonian brain and that their elevation is involved
      in the degeneration of the nigrostriatal dopaminergic neurons.

PMID- 17196750
TI  - Role of peripheral hyperpolarization-activated cyclic nucleotide-modulated
      channel pacemaker channels in acute and chronic pain models in the rat.
AB  - Hyperpolarization-activated, cyclic nucleotide-modulated (HCN) channels
      contribute to rhythmic spontaneous activity in the heart and CNS. Ectopic
      spontaneous neuronal activity has been implicated in the development and
      maintenance of acute and chronic hyperalgesia, allodynia and spontaneous pain.
      Previously, we documented that systemic administration of ZD7288, a specific
      blocker of pacemaker current (I(h)), decreased ectopic activity in dorsal root
      ganglion (DRG) and reversed tactile allodynia in spinal nerve ligated (SNL) rats
      [Chaplan SR, Guo HQ, Lee DH, Luo L, Liu C, Kuei C, Velumian AA, Butler MP, Brown
      SM, Dubin AE (2003) Neuronal hyperpolarization-activated pacemaker channels drive
      neuropathic pain. J Neurosci 23:1169-1178]. Spontaneous pain is the chief
      clinical manifestation of peripheral nerve injury; however, a role for I(h) in
      spontaneous pain has not been described. Here, in further rat studies, we report
      that systemic administration of ZD7288 reversed spontaneous pain induced by mild
      thermal injury (MTI) and tactile allodynia induced by SNL and MTI. In contrast,
      ZD7288 did not reduce thermal hyperalgesia. An important locus of action appears
      to be in the skin since intraplantar (local) administration of ZD7288 completely
      suppressed tactile allodynia arising from MTI and SNL and reduced spontaneous
      pain due to MTI. Immunohistochemical staining of plantar skin sections detected
      HCN1-HCN4 expression in mechanosensory structures (e.g., Meissner's corpuscles
      and Merkel cells). Collectively, these data suggest that expression and
      modulation of I(h) in the peripheral nervous system, including specialized
      sensory structures, may play a significant role in sensory processing and
      contribute to spontaneous pain and tactile allodynia.

PMID- 17196752
TI  - Drug dependent parents: childcare responsibilities, involvement with treatment
      services, and treatment outcomes.
AB  - Relatively little is known about the treatment of drug dependent parents. This
      study of drug misusers (n=1075) investigates the involvement of parents with
      treatment services, childcare arrangements before and during treatment, and
      outcomes at 1-year follow up. Almost half the sample (46%) were parents. Women
      were more likely to be responsible for the care of children. Parents, and
      especially women, who looked after children, were less likely to receive
      residential treatment. Illicit drug use and psychiatric symptoms were reduced at
      1 year. Outcomes did not differ by gender or parenting status, but there was an
      interaction effect for psychiatric symptoms: for women, looking after children
      during treatment was associated with less improvement in psychiatric symptoms at
      follow up. Such women face special difficulties in access to services and would
      benefit if treatment services were able to offer improved access and childcare
      support.

PMID- 17196753
TI  - Small vessel avulsion and acute aortic syndrome: a putative aetiology for
      initiation and propagation of blunt traumatic aortic injury at the isthmus.
AB  - Based on literature, clinical observation and the analysis of material properties
      of the aorta, we hypothesize that the aortic isthmus is intrinsically susceptible
      to blunt trauma because it has a higher density of tributary vessels than other
      elements of the aortic tree, the avulsion of which during trauma, is a
      contributory factor in the development of an acute aortic syndrome resulting from
      intra-mural haematoma, localized dissection and ultimately rupture. This
      hypothesis provides putative explanations for several aspects of the injury
      profile including: localized peri-isthmus injuries, inside out injury profiles
      and the concept of initiation versus propagation of blunt traumatic aortic
      injury.

PMID- 17196751
TI  - Relationships between locomotor activation and alterations in brain temperature
      during selective blockade and stimulation of dopamine transmission.
AB  - It is well known that the dopamine (DA) system plays an essential role in the
      organization and regulation of brain activational processes. Various
      environmental stimuli that induce locomotor activation also increase DA
      transmission, while DA antagonists decrease spontaneous locomotion. Our previous
      work supports close relationships between locomotor activation and brain and body
      temperature increases induced by salient environmental challenges or occurring
      during motivated behavior. While this correlation was also true for psychomotor
      stimulant drugs such as methamphetamine and MDMA, more complex relationships or
      even inverted correlations were found for other drugs that are known to increase
      DA transmission (i.e. heroin and cocaine). In the present study we examined
      brain, muscle and skin temperatures together with conventional locomotion during
      selective interruption of DA transmission induced by a mixture of D1 and D2
      antagonists (SCH-23390 and eticlopride at 0.2 mg/kg, s.c.) and its selective
      activation by apomorphine (APO; 0.05 and 0.25 mg/kg, i.v.) in rats. While full DA
      receptor blockade decreased spontaneous locomotion, it significantly increased
      brain, muscle and skin temperatures, suggesting metabolic brain activation under
      conditions of vasodilatation (or weakening of normal vascular tone). In contrast,
      APO strongly decreased skin temperature but tended to decrease brain and muscle
      temperatures despite strong hyperlocomotion and stereotypy. The brain temperature
      response to APO was strongly dependent on basal brain temperature, with
      hypothermia at high basal temperatures and weak hyperthermia at low temperatures.
      While supporting the role of DA in locomotor activation, these data suggest more
      complex relationships between drug-induced alterations in DA transmission,
      behavioral activation and metabolic brain activation.

PMID- 17196754
TI  - Bimodal age distribution in Hodgkin's disease and nasopharyngeal carcinoma.

PMID- 17196755
TI  - Glatiramer acetate could be a potential antidepressant through its
      neuroprotective and anti-inflammatory effects.
AB  - Antidepressants that act by increasing the activity of central serotonergic or
      noradrenergic systems are the main biological treatments for major depressive
      disorder (MDD). Although these agents are generally safe and effective, they are
      far from ideal due to their slow onset and a substantial proportion of MDD
      patients do not clinically improve, despite maximal dosing. Thus, the development
      of new antidepressants based on novel theories may help to develop faster and
      more effective antidepressant agents. Over the last decade, there has been an
      impressive accumulation of data about non-monoamine systems that might mediate
      the pathogenesis of, and therapeutic mechanisms in, MDD. For example, MDD has
      been associated with a decreased central brain-derived neurotrophic factor (BDNF)
      state and activating the BDNF-signaling pathway may play an important role in the
      mechanisms of antidepressant therapeutic action. Glatiramer acetate (GA) is a
      collection of synthetic polypeptides indicated as therapy for relapsing-remitting
      multiple sclerosis. Both preclinical and clinical studies have demonstrated that
      peripheral GA administration can enhance central BDNF activity or increase serum
      BDNF levels. Furthermore, MDD has been associated with an inflammatory process in
      the brain. Animal studies have demonstrated that GA administration has a central
      anti-inflammatory effect through the release of interleukin-10. Finally, recent
      animal studies have suggested that psychosocial stress reduces neurogenesis,
      whereas antidepressant treatment increases neurogenesis and blocks the effects of
      stress. Peripheral administration of GA was found to augment neurogenesis,
      including cell proliferation, migration, and differentiation in rodent brain.
      From the above evidence, GA could have antidepressant effects by increasing
      central BDNF, stimulating neurogenesis or through its anti-inflammatory effect.
      It is also suggested that immediate GA treatment after stress may prevent the
      development of stress-related psychiatric disorders such as MDD and post
      traumatic stress disorder.

PMID- 17196756
TI  - Eradication of Helicobacter pylori might halt the progress to oesophageal
      adenocarcinoma in patients with gastro-oesophageal reflux disease and Barrett's
      oesophagus.

PMID- 17196757
TI  - Hyperbolic discounting may be reduced to electrical coupling in dopaminergic
      neural circuits.
AB  - Loss of self-control in drug addicts (e.g. cocaine and amphetamine dependent
      patients) has been associated with hyperbolic discounting of delayed rewards
      (i.e., inconsistency in intertemporal choice). Neurobiophysical mechanisms
      underlying hyperbolic discounting are still unknown in spite of recent extensive
      work in neuroeconomics. Understanding of neuronal mechanisms of hyperbolic
      discounting is important for establishing neuropharmacological treatment of
      addiction. At the cognitive level, previous studies have indicated that
      psychophysics of time-estimation (i.e., Weber-Fechner law and Steven's power law
      of time-perception) may explain inconsistency in intertemporal choice. Regarding
      neuronal substrates of time-estimation, drugs of abuse dramatically change time
      estimation, indicating that dopaminergic activities may mediate time-estimation.
      With respect to neuronal changes induced by drugs of abuse, recent studies have
      revealed that gap junction proteins (e.g., connexin 36) in dopamine neurons are
      increased by an self-administration of dopaminergic drugs such as cocaine and
      amphetamine. However, it has been yet to be examined how the enhanced electrical
      coupling due to substance administration induces addiction. Furthermore, a recent
      biophysical modelling study has demonstrated that the effect of the
      psychophysical laws are potentiated by non-synaptic electrical coupling between
      neurons via gap junctions. Based on these current findings, we hypothesized that
      hyperbolic discounting may be reduced to biophysical characteristics of dopamine
      neural circuits, that is, electrical coupling between time-encoding dopaminergic
      neurons via gap junctions. The present hypothesis states that drugs of abuse may
      induce addiction by exacerbating subject's impulsivity (a discount rate) and
      inconsistency (hyperbolicity) in intertemporal choice partly due to enhanced
      expression of gap junction proteins in dopaminergic neurons. Possible
      psychopharmacological treatments of impulsivity in drug addicts implied by our
      present hypothesis, e.g., administration of a gap junction blocker, are
      discussed.

PMID- 17196758
TI  - Parvovirus B19 infection of brain: possible role of gender in determining mental
      illness and autoimmune thyroid disorders.
AB  - Major theories about the etiologies of chronic mental illnesses such as bipolar
      disorder and schizophrenia include genetic and environmental factors such as
      famine and infection. It is likely that multiple genes play a role in the
      pathogenesis of these disorders, but no single gene has been identified as
      causative. Several viruses have been investigated as potential candidates, but
      conflicting reports exist. Although a relationship between bipolar disorder and
      schizophrenia with autoimmune disorders has also been documented for many years,
      reports are often conflicting. We hypothesize that parvovirus B19 (B19), a common
      human pathogen, due to its ability to infect the brain and induce autoimmunity,
      is a strong candidate that may unite prevailing theories. In particular, our
      preliminary data suggest that B19 may be most likely involved in co-morbid
      bipolar and autoimmune thyroid disorders in females. In schizophrenics, the
      gender trend may be reversed. We propose that there is a complex interaction
      between immuno-genetics, autoimmunity, gender, and B19 infection that leads to at
      least some forms of bipolar disorder and schizophrenia. Future studies that
      investigate this hypothesis are warranted and outlined.

PMID- 17196759
TI  - Is rug shampoo forgotten but continuing risk factor for Kawasaki disease?

PMID- 17196760
TI  - Therapeutic implication of cocaine- and amphetamine-regulated transcript (CART)
      in the treatment of depression.
AB  - Despite the fact that antidepressants represent the gold standard for the
      treatment of depression, not all patients treated with an antidepressant
      monotherapy achieve complete remission of depressive symptoms and functional
      recovery. Therefore, further examination of the components that may be involved
      in the action mechanism of antidepressants will benefit patients who show either
      no response or partial response by identifying their hidden functions and key
      roles in the therapeutic mechanism of antidepressants. The cocaine- and
      amphetamine-regulated transcript (CART), which is a brain-enriched mRNA with a
      protein product(s) is an interesting neuropeptide in relation to the treatment of
      depression. CART mRNA is strongly expressed in the major limbic structures that
      modulate affect and anxiety as well as being a possible key target for the action
      of antidepressants. A bidirectional relationship between CART and the
      hypothalamic-pituitary-adrenal (HPA) axis activity has been accepted to date,
      which suggests that CART might efficiently bridge the interaction between the
      stress-related events and the neurobehavioral response. The regulation of the
      signal transduction pathways by CART by modulating neurotrophic factors, such as
      brain-derived neurotrophic factor (BDNF), kinases (trkB), and neurotransmitters
      (5-HT), can also contribute to the treatment of depression. It might have an
      augmenting effect in the treatment of depression because it acts as a putative
      and potential neurotransmitter/cotransmitter that is involved in psychostimulant
      action as well. Finally, preliminary results suggest that CART directly controls
      the expression of major neurotransmitters such as serotonin, noradrenaline, and
      dopamine. Hence, further studies on therapeutic implications of CART for
      depression are warranted and will contribute to the development of newer
      selective antidepressants.

PMID- 17196761
TI  - Ex vivo expanding hematopoietic stem cells by intracellular delivery of Cdx4
      fusion proteins.
AB  - Hematopoietic stem cells transplantation has been wildly used in clinical
      settings and has shown exciting results in treating a wide variety of diseases.
      However, the relative small number of hematopoietic stem cells in bone marrow,
      even lower in peripheral or umbilical cord blood limits its clinical utility.
      There are several protocols, which have been developed to expand hematopoietic
      stem cells to reach clinical goal. With the recent insights into the mechanisms
      of hematopoietic stem cells self-renewal, we postulate that Cdx4, which is coded
      by one of the caudal related homeobox genes and regulates the expression of hox
      genes, could fuse with protein transduction domains, thereby get the ability to
      cross cellular membrane. And the recombinant fusion proteins could be used in
      expanding hematopoietic stem cells. Meanwhile, Cdx4 fusion proteins would be more
      efficient than other methods that had been developed for it can up-regulate a
      cocktail of hox genes, which has been proved to be capable of amplifying
      hematopoietic stem cells. It would provide us an alternative protocol to amplify
      hematopoietic stem cells if the hypothesis proved to be practical.

PMID- 17196762
TI  - Cancer dissemination: a consequence of limited carrying capacity?
AB  - Assuming that there is feedback between an expanding cancer system and its organ
      typical microenvironment, we argue here that such local tumor growth is initially
      guided by co-existence rather than competition with the surrounding tissue. We
      then present a novel concept that understands cancer dissemination as a
      biological mechanism to evade the specific carrying capacity limit of its host
      organ. This conceptual framework allows us to relate the tumor system's
      volumetric growth rate to the host organ's functionality-conveying composite
      infrastructure, and, intriguingly, already provides useful insights into several
      clinical findings.

PMID- 17196764
TI  - Statin use to prevent aromatase inhibitor-induced fracture and cardiovascular
      complications.

PMID- 17196763
TI  - Rembrandt: one idea, two pictures.

PMID- 17196765
TI  - Atopic dermatitis and anxiety: possible role of brain-derived neurotrophic factor
      (BDNF).

PMID- 17196766
TI  - Lysozyme and similar lytic enzyme preparations should be considered antibiotics.

PMID- 17196768
TI  - Frequent emergence and functional resurrection of processed pseudogenes in the
      human and mouse genomes.
AB  - Despite the wide distribution of processed pseudogenes in mammalian genomes, such
      as those of human and mouse, relatively little is known about their roles in
      genomic evolution. While gene duplications are recognized as one of the major
      driving forces in genome evolution, processed pseudogenes, which are
      retrotransposed copies of mRNAs, have been regarded as junk or selfish DNA for a
      long time. In order to elucidate the quantitative and qualitative contribution of
      processed pseudogenes to the mammalian genome evolution, we attempted to detect
      processed pseudogenes by extensively mapping the mRNAs to both the human and
      mouse genomes, and then we estimated the rate of their emergence. As a result, we
      revealed that the rate of pseudogene emergence was about 1-2% per gene per
      million years, which was as high as the rate (0.9%) of gene duplication in the
      human genome, although the rate of pseudogene emergence was found to drastically
      decrease in the hominid lineage. Furthermore, 1% of the processed pseudogenes
      seemed to be reinvigorated by post-retrotransposition transcription, many of them
      preserving the intact coding regions. Since the expression patterns of
      transcribed pseudogenes in various tissues were quite different between human and
      mouse, their emergence might have led to species-specific evolution. Our results
      indicate that the generation of processed pseudogenes was not wholly futile but
      instead has been an indispensable resource, driving dynamic evolution of the
      mammalian genomes.

PMID- 17196767
TI  - Antibacterial activity of Abies webbiana.
AB  - The methanol extract of the dried leaves of Abies webbiana was evaluated for
      antimicrobial activity. The methanol extract showed a broad spectrum of
      antibacterial activity.

PMID- 17196769
TI  - Analysis of genetic elements regulating the methionine adenosyltransferase gene
      in Leishmania infantum.
AB  - Methionine adenosyltransferase (MAT) is an important enzyme for metabolic
      processes, inasmuch as its product, S-adenosylmethionine (AdoMet), plays a key
      role in trans-methylation, trans-sulphuration and polyamine synthesis. Our prior
      studies have shown that the Leishmania infantum genome contains two identical
      copies of the gene encoding MAT (MAT2 gene), arranged in head-to-tail
      configuration and alternating with another gene, called LORIEN that contains a
      zinc-finger motif. Both genes are constitutively expressed throughout the
      promastigote stage of the parasite cell cycle, and their flanking regions were
      detected by RT-PCR. Luciferase (luc) reporter assays indicated the presence of
      regulatory elements within the MAT2 3'UTR and intergenic region, and fragments
      responsible for such regulation were identified by deletional analysis. By site
      directed mutagenesis of the wild-type -42 AG recognized in the trans-splicing of
      the MAT2 gene, the AG slightly downstream (position -36) was observed to be able
      to generate the same levels of luc expression, thus suggesting that potentially
      this gene has alternative spliced leader acceptor sites. The stability of MAT2
      and LORIEN transcripts was very similar in both logarithmic and stationary
      phases. However, cycloheximide (CHX) inhibition of protein synthesis increased
      MAT2 and LORIEN mRNA levels in the logarithmic phase only, an indication that
      these genes are regulated in promastigotes at the post-transcriptional level by
      protein factors that targets both transcripts for degradation. However, during
      the stationary phase, another CHX-independent factor also led to MAT2 and LORIEN
      mRNAs degradation, indicating the existence of different mechanisms operating on
      the post-transcriptional regulation of these two genes.

PMID- 17196770
TI  - Sequence and expression of four coral G protein-coupled receptors distinct from
      all classifiable members of the rhodopsin family.
AB  - A measure of the functional importance of G protein-coupled receptors (GPCRs) as
      signalling molecules is that over seven hundred have been cloned and identified
      in the human genome alone. Yet few have been characterized in the lower metazoan
      phyla, especially in the phylum Cnidaria which is well positioned
      phylogenetically for tracing the early evolution of GPCRs owing to their
      possession of the first-evolved nervous systems. We report here the cloning and
      characterization of four novel rhodopsin-like GPCR cDNAs from the staghorn coral
      Acropora millepora that share significant similarity with each other but not with
      the majority of other members of the rhodopsin alpha subfamily. The deduced
      proteins lack many of the conserved residues and motifs that form the signature
      of the different groups of alpha rhodopsin receptors. Maximum likelihood
      phylogenetic analysis likewise implies that the coral receptors do not have a
      simple or close relationship with any of the major groups within the alpha
      rhodopsin subfamily. In situ hybridization revealed transcripts in endodermal
      cells of planula larvae of all ages and in post-settlement polyps. These GPCRs
      appear to belong to a alpha rhodopsin-like group unique to corals. Comparisons
      with other cnidarian GPCRs suggest also that GPCRs diverged early in metazoan
      evolution.

PMID- 17196771
TI  - Differential tissue/organ-dependent expression of two sucrose- and cold
      responsive genes for UDP-glucose pyrophosphorylase in Populus.
AB  - Plant UDP-glucose (UDPG) pyrophosphorylase (UGPase) is involved in the
      production/metabolism of UDPG, a key metabolite for sucrose and cell wall
      biosynthesis. Two highly similar cDNAs (UGP1 and UGP2) corresponding to UGPase
      were isolated from cDNA libraries of hybrid aspen (Populus tremula x
      tremuloides). Expression of both UGPs, as studied by DNA microarrays and EST
      abundance, was compared to that of three sucrose synthase genes (SUS1-3), also
      involved in UDPG synthesis. Generally, the UGPs had lower expression than SUS1
      and SUS2 genes (especially in tension wood and cambium), with the notable
      exception of leaves, primary roots and flowers. Based on real-time quantitative
      PCR, UGP1 in root xylem, leaves and male flowers was by far the predominant
      transcript, while in other tissues both UGP1 and UGP2 had comparable expression.
      In leaves, the UGP1 gene, but not UGP2, was upregulated by light and short-term
      sucrose feeding. Cold treatment led to dramatic organ-specific changes in
      relative expression of both genes, with UGP2 being upregulated either transiently
      (leaves), long-term (stems) or not at all (roots), whereas UGP1 was cold
      upregulated in all organs. Individual or overall UGP expression patterns only
      weakly correlated with UGPase activity/protein; however, UGPase activity and
      protein were correlated in all tissues/conditions. The data suggest that UGPs are
      differentially expressed at the tissue level and in response to metabolic
      feedback (sucrose) and cold stress, and point to a tight
      posttranscriptional/translational control and, possibly, distinct roles for those
      genes.

PMID- 17196772
TI  - Screening infants with an isolated single umbilical artery for renal anomalies:
      nonsense?
AB  - BACKGROUND: Presently there is no consensus regarding the extent of workup
      required in newborns who present with an isolated single umbilical artery (SUA).
      Because of the association with silent renal anomalies, some studies advise to
      perform renal ultrasonography in infants born with an isolated SUA. AIMS: To
      decide whether screening (performing a renal ultrasound and in case of
      abnormalities on the ultrasound performing a micturating cystourethrogram)
      infants with an isolated SUA is justified by evaluating the prevalence of
      clinically relevant renal abnormalities. STUDY DESIGN: Retrospective descriptive
      study. SUBJECTS: Live-born infants with SUA detected by physical examination born
      between January 1st, 1997 and February 1st, 2005, in a tertiary care university
      hospital. OUTCOME MEASURES: Renal anomalies detected by renal ultrasonography and
      a micturating cystourethrogram in infants with abnormalities on renal ultrasound.
      RESULTS: We included 52 live-born infants with an isolated SUA. Renal
      ultrasonography was performed in 92.3% of these 52 infants. In this group,
      abnormalities were found in 5 infants (10.4 %) on renal ultrasound. A relative
      subpelvine stenosis was detected in 1 infant, the other abnormalities on renal
      ultrasound were mild hydronephrosis without further consequences. CONCLUSION: Our
      data suggest that it is not necessary to screen for renal anomalies in infants
      with a single umbilical artery without other anomalies seen at physical
      examination.

PMID- 17196773
TI  - Developmental effects on neonatal mortality and subsequent cerebral palsy in
      infants exposed to intrauterine infection.
AB  - BACKGROUND: Intrauterine bacterial infection is important as a high risk factor
      associated with subsequent brain damage of the newborn. AIMS: To see if mature
      fetuses require both hypoxia and intrauterine infection to lead to cerebral
      palsy, while premature fetuses need infection alone. STUDY DESIGN: A
      retrospective cohort study. SUBJECTS: 230 singleton live-born infants of 22 to 32
      weeks of gestation, exposed to intrauterine infection during labor and delivery,
      from 1995 to 2002. METHODS: Mortality and incidence of cerebral palsy at 2 years
      old were compared among the 3 groups; immature (n=89, 22-27 weeks), premature
      (n=73, 28-33 weeks) and mature (n=68, >34 weeks). The relationship between
      cerebral palsy and fetal pH values was examined. OUTCOME MEASURES: Mortality and
      cerebral palsy. RESULTS: Mortality and cerebral palsy were significantly
      decreased with advancing gestation. Mortality was significantly decreased after
      28 weeks of gestation while cerebral palsy was significantly decreased after 34
      weeks of gestation. Acidosis was associated with cerebral palsy in mature
      infants, but not in less mature infants. CONCLUSIONS: : Premature infants were
      more susceptible to intrauterine infection to cause death or cerebral palsy than
      mature infants. Mature infants may require exposures to both infection and
      hypoxia but less mature infants need infection alone to cause cerebral palsy,
      suggesting different pathogenesis during the developmental stage.

PMID- 17196774
TI  - Novel pharmaceutical composition of bradykinin potentiating penta peptide with
      beta-cyclodextrin: physical-chemical characterization and anti-hypertensive
      evaluation.
AB  - This work describes chemical properties and anti-hypertensive activity of an oral
      pharmaceutical formulation obtained from the complexation of beta-cyclodextrin
      (beta-CD) with bradykinin potentiating penta peptide (BPP-5a) founded in the
      Bothrops jararaca poison. Physical chemistry characterizations were recorded in
      order to investigate the intermolecular interactions between species in complex.
      Circular dichroism data indicated conformational changes of BPP-5a upon
      complexation with beta-CD. ROESY and theoretical calculations showed a selective
      approximation of triptophan moiety into cavity of beta-CD. Isothermal titration
      calorimetry data indicated an exothermic formation of the complex, which is
      accomplished by reduction of entropy. The anti-hypertensive activity of the BPP
      5a/beta-CD complex has been evaluated in spontaneous hypertensive rats, showing
      better results than pure BPP-5a.

PMID- 17196775
TI  - Effect of preparation method on compactability of paracetamol granules and
      agglomerates.
AB  - The objective of this study was to investigate the effect of fracture strength of
      paracetamol particles on their compactability. For this purpose two series of
      paracetamol particles were prepared by crystal agglomeration and by granulation
      using different solvents. A free flowing particle size fraction of all types of
      particles was characterized with respect to their shape, degree of agglomeration
      and single fracture strength. The powders were compressed to tablets and the
      compression mechanism of the particles and the evolution in tablet micro
      structure were assessed by compression parameters derived from the Heckel and
      Kawakita equations and by a tablet permeabililty coefficient. Tablet tensile
      strength and porosity were determined. The degree of deformation and
      fragmentation during compression varied between agglomerates and granules and was
      dependent on their failure strength. The granules varied in compactability with
      particle failure strength while the agglomerates showed limited variation. It is
      proposed that, the dominant mechanism of compression for the granules was
      permanent deformation while for the agglomerates it was fragmentation. It was
      thus found that the compression mechanism of the particles was dependent on both
      the degree of agglomeration and the particle failure strength.

PMID- 17196776
TI  - Plants of restricted use indicated by three cultures in Brazil (Caboclo-river
      dweller, Indian and Quilombola).
AB  - A detailed record of plants cited during ethnopharmacological surveys, suspected
      of being toxic or of triggering adverse reactions, may be an auxiliary means to
      pharmacovigilance of phytomedicines, in that it provides greater knowledge of a
      "bad side" to plant resources in the Brazilian flora. This study describes 57
      plant species of restricted use (abortive, contraceptive, contraindicated for
      pregnancy, prescribed in lesser doses for children and the elderly, to easy
      delivery, in addition to poisons to humans and animals) as indicated during
      ethnopharmacological surveys carried out among three cultures in Brazil (Caboclos
      river dwellers, inhabitants of the Amazon forest; the Quilombolas, from the
      pantanal wetlands; the Kraho Indians, living in the cerrado savannahs). These
      groups of humans possess notions, to a remarkable extent, of the toxicity,
      contraindications, and interaction among plants. A bibliographical survey in the
      Pubmed, Web of Science and Dr. Duke's Phytochemical and Ethnobotanical Databases
      has shown that 5 out of the 57 species have some toxic properties described up to
      the present time, they are: Anacardium occidentale L. (Anacardiaceae), Brosimum
      gaudichaudii Trecul (Moraceae), Senna alata (L.) Roxb. (Fabaceae), Senna
      occidentalis (L.) Link (Fabaceae), Strychnos pseudoquina A. St.-Hil.
      (Loganiaceae) and Vernonia brasiliana (L.) Druce (Asteraceae).

PMID- 17196777
TI  - Effect of hyaluronic acid and polysaccharides from Opuntia ficus indica (L.)
      cladodes on the metabolism of human chondrocyte cultures.
AB  - Conventional medications in articular disease are often effective for symptom
      relief, but they can also cause significant side effects and do not slow the
      progression of the disease. Several natural substances have been shown to be
      effective as non-steroidal anti-inflammatory drugs at relieving the symptoms of
      osteoarthritis (OA), and preliminary evidence suggests that some of these
      compounds may exert a favourable influence on the course of the disease. In this
      study, we assay the anti-inflammatory/chondroprotective effect of some
      lyophilised extracts obtained from Opuntia ficus indica (L.) cladodes and of
      hyaluronic acid (HA) on the production of key molecules released during chronic
      inflammatory events such as nitric oxide (NO), glycosaminoglycans (GAGs),
      prostaglandins (PGE(2)) and reactive oxygen species (ROS) in human chondrocyte
      culture, stimulated with proinflammatory cytokine interleukin-1 beta (IL-1 beta).
      Further the antioxidant effect of these extracts was evaluated in vitro employing
      the bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test).
      All the extracts tested in this study showed an interesting profile in active
      compounds. Particularly some of these extracts were characterized by polyphenolic
      and polysaccharidic species. In vitro results pointed out that the extracts of
      Opuntia ficus indica cladodes were able to contrast the harmful effects of IL-1
      beta. Our data showed the protective effect of the extracts of Opuntia ficus
      indica cladodes in cartilage alteration, which appears greater than that elicited
      by hyaluronic acid (HA) commonly employed as visco-supplementation in the
      treatment of joint diseases.

PMID- 17196778
TI  - The relationship between alcohol elimination rate and increasing blood alcohol
      concentration--calculated from two consecutive blood specimens.
AB  - In the period 1991-2005, a blood-alcohol concentration (BAC) analysis was carried
      out at the Institute of forensic medicine in Novi Sad including 2023 two
      consecutive blood specimens using the Headspace Gas Chromatography method. Cases
      with no alcohol concentration values, as well as cases where blood samples were
      taken within 1 h after the criminal act, were not taken into consideration.
      Following this rule, 1198 cases were considered in this study and all samples
      were grouped in 29 ranges of BAC1 of delta(BAC) = 0.1 g/kg, starting from 0.1
      0.19 g/kg to 2.9-2.99 g/kg of absolute alcohol. Gathered results and elimination
      curve differ from the zero-order model of elimination proposed by Widmark and
      point to an elimination process similar to a well-known Michaelis-Menten
      elimination kinetics model and its variants. Results reported in this study show
      dependence of alcohol elimination rate (beta-slope) and BAC value. The analysis
      of beta60-slope versus BAC shows that a correlation between beta60 (y) and BAC
      (x) has a logarithmic trend line. The value of alcohol elimination rate shows a
      slight increment with increase of BAC alcohol, with the mean value of beta60 =
      0.221 +/- 0.075 g/kg. Differences in values of beta60 among consecutive intervals
      of delta(BAC) = 0.1 g/kg are not significant (p>0.05). When obtained samples were
      grouped into ranges of 0.5 g/kg each in these intervals beta60 had the following
      values by range: 0.1-0.49 g/kg = 0.139 g/kg +/- 0.035; 0.5-0.99 g/kg = 0.184 g/kg
      +/- 0.043; 1-1.49 g/kg = 0.213 g/kg +/- 0.052; 1.5-1.99 g/kg = 0.239 g/kg +/-
      0.058; 2-2.49 g/kg = 0.265 g/kg +/- 0.073; 2.5-2.99 g/kg = 0.306 g/kg +/- 0.096.
      Differences in values of beta slope among consecutive intervals of delta(BAC) =
      0.5 g/kg are significant (p<0.01). The elimination curve in the BAC interval 0.5
      2.5 g/kg has a linear trend, while beta-slope (y)/BAC (x) correlation is given as
      beta60 = 0.15 g/kg + (0.05 g/kg x BAC). Retrograde calculation of the blood
      alcohol concentration in tempore criminis (BAC(tc)) based on the determined
      alcohol concentration in the blood specimen (BAC(t)) shows a statistically
      significant difference between BAC(tc) calculated using a standard zero-order
      model versus corrected methodology. The higher the BAC(t) and the longer the
      calculation time, the greater and statistically more significant (p<0.01) is the
      difference between the calculated values of BAC(tc).

PMID- 17196779
TI  - A case of cerebellar infarction caused by vertebral artery injury from a stab
      wound to the neck.
AB  - Vertebral artery injuries are the least common arterial injuries because of the
      deep location of the vessel in a bony canal. Injury of this vessel has not been
      associated with neurological deficits, and it is thought that many of these
      injuries are not recognized. The incidence of vertebral artery injury occurring
      after a penetration wound to the neck varies from 1.0% in gunshot wounds to 7.4%
      in stab wounds. However, even with vertebral artery injury in penetration wounds
      of the neck the association with cerebellar infarction is a rare occurrence. We
      describe a case of cerebellar infarction caused by vertebral artery injury from a
      stab wound that severed the vessel between the transverse processes of C3 and C4
      with a hypoplastic contralateral vertebral artery. The patient ultimately
      suffered infarction of the cerebellum due to the lack of preservation of the
      posterior inferior cerebellar artery blood flow. Management is discussed and the
      medical literature is reviewed.

PMID- 17196780
TI  - Investigation of Helicobacter pylori in tonsillary tissue with Pronto Dry test
      and pathologic examination.
AB  - OBJECTIVE: The objectives of this clinical study were to identify, by means of
      the Pronto Dry test and pathologic examination, Helicobacter pylori (HP) in
      tonsillary tissue and to establish the role of HP in tonsillary microbiology by
      identifying that bacterium in the tonsillary mucosa or within the tonsil core.
      METHODS: The subjects consisted of 52 patients (25 men and 27 women; age range, 3
      65 years; mean age, 15.1+/-14.5 years) who were scheduled to undergo
      tonsillectomy for the treatment of chronic tonsillitis and who had not been
      treated with an antibiotic or a bismuth-containing compound for 6 months before
      the initiation of the study. In each patient, two specimens (one 4 mm x 4 mm
      tissue sample from the nonmucosal tonsil core and one 4 mm x 4 mm sample of
      mucosal tissue) were excised from both tonsils immediately after tonsillectomy.
      The specimens were placed in the Pronto Dry test kit, and the test results were
      obtained 1 h later. The remaining tonsillary tissues were submitted for
      pathologic analysis via hematoxylin-eosin stain, Giemsa stain, Warthin-Starry
      silver stain, and staining for inducible nitric oxide synthase (iNOS). RESULTS:
      The results of the Pronto Dry test were positive for HP in 42% (n=22) of the
      excised mucosal tissue and in 47% (n=24) of the excised core tissue. In 27%
      (n=14) of the patients, both the core and the mucosal tissues tested positive for
      HP. There was no significant difference between the positive Pronto Dry test
      ratios of the biopsies obtained from the mucosa and those obtained from the core
      (P=0.693). iNOS staining showed that macrophage iNOS activity was significantly
      higher (P=0.025) in biopsied mucosal tissues with a positive Pronto Dry test
      result than in those with a negative result. Light microscopy revealed no HP in
      samples stained with hematoxylin-eosin stain, Giemsa stain, or Warthin-Starry
      silver stain. CONCLUSION: Positive Pronto Dry test results and the results of
      iNOS staining showed that HP contributes to chronic tonsillitis, especially at
      the mucosal layer. Although HP does not colonize, it contributes to the chronic
      tonsillary inflammatory process as a triggering agent by affecting macrophages in
      the tonsil and thus increasing iNOS expression.

PMID- 17196782
TI  - Properties and exploitation of oleosins.
AB  - Oleosins stabilize oil bodies in seeds and other tissues and contain a unique
      hydrophobic domain which appears to be inserted into the oil matrix as an alpha
      helical hairpin. The oleosin proteins may be exploited to stabilize emulsions
      while the ease of oil body preparation has led to the expression of bioactive
      proteins as oleosin fusions in molecular farming.

PMID- 17196783
TI  - Biocatalysts: measurement, modelling and design of heterogeneity.
AB  - Multiple phenomena are involved in conversions by immobilized biocatalysts. A
      paradox is identified between analytical desires on one hand and analytical
      boundary conditions on the other: while the study of interdependent phenomena
      would call for their simultaneous analysis in an integrated context, the
      available experimental options may impose a series of separate and dedicated
      analyses. From this analysis, bottlenecks in particle performance may be
      identified, if possible supported by a mechanistic model and performance
      criteria. Subsequently, a strategy for further biocatalyst development may be
      chosen. Finally, possibilities for future improvement of biocatalysts are
      discussed for various fields of research. Some examples of recent developments in
      enzyme and matrix characteristics, reactor operation, and micro-technology are
      discussed.

PMID- 17196781
TI  - [Principles of an outbreak investigation in public health practice].
AB  - An outbreak (or epidemic) is a higher number of cases of a given disease in a
      given population and time interval. A timely investigation has for aim to
      identify the source and vehicle of the outbreak and provides unique opportunities
      to better understand its occurrence and the role of contributing risk factors to
      implement the most appropriate measures to control it and prevent further
      recurrences. The investigation of an outbreak is based on a multidisciplinary
      approach (clinical, epidemiological, environmental, and microbiological) with a
      descriptive and analytical (hypothesis testing) phase. In this article, we
      describe the methodological approach of a field outbreak investigation
      illustrated by examples taken from our experience. The investigation includes the
      following steps: establishing the existence of the outbreak; defining the
      disease; finding cases; describing cases by time, place, and person
      characteristics; establishing a hypothesis related to the mode of occurrence;
      testing the hypotheses; conducting an environmental investigation; conducting a
      microbiological investigation; controlling the outbreak, preventing further
      occurrences, and writing an investigation report to share experience with the
      public health and scientific community. The investigation of an outbreak is an
      evolving process: information gathered or conclusions made at a given stage must
      be fully used for following steps. The social, institutional, and political
      background associated with outbreaks usually makes their investigation complex
      and should be taken into account. The earlier the outbreak is detected and
      investigated in close relation with public health authorities, the greater will
      be the potential preventive impact of control measures.

PMID- 17196784
TI  - Plant lipid binding proteins: properties and applications.
AB  - Lipid transfer proteins (LTP) and puroindolines are abundant lipid binding
      proteins of plant seeds. While LTP are ubiquitous plant proteins, puroindolines
      are only found in the seeds of plants from the Triticae and Avenae tribes. These
      proteins display a similar overall folding pattern but different lipid binding
      properties. The unique and diverse biological and technological functions of LTPs
      and puroindolines are closely related to their structural and lipid binding
      properties. These proteins are attractive to improve the agronomic performances
      and food quality of crops. Heterologous expression and genetic engineering should
      allow industrial production and enlarge applications of these lipid binding
      proteins.

PMID- 17196785
TI  - Use and employer costs of a pharmacotherapy smoking-cessation treatment benefit.
AB  - BACKGROUND: Employers cite a lack of information on the cost of insurance
      coverage for smoking-cessation treatment as a barrier to its provision. This
      study describes the use of a new insurance benefit for smoking-cessation
      pharmacotherapy, and its pharmaceutical costs to a large public employer between
      2001 and 2003. METHODS: Annual enrollment and pharmaceutical claims data were
      collected from the health plans that contracted with the Wisconsin Department of
      Employee Trust Funds (ETF). State employees, retirees, and adult dependents who
      obtained health insurance through the ETF constituted our sample, approximately
      150,000/year. Pharmacotherapy benefit use was defined as a paid claim for one of
      four U.S. Food and Drug Administration-approved smoking-cessation medications.
      Pharmaceutical cost was defined as the ingredient cost (+) dispensing fee (-)
      member copayment. Analyses included estimation of the proportion of smokers who
      used the benefit each year and across 3 years, the average annual cost per user,
      and the per member per month (PMPM) pharmaceutical cost to the employer. Data
      were collected from 2001 to 2004 and analyzed in 2005-2006. RESULTS: Annual
      benefit use among smokers ranged from 6% to 7% with a 3-year rate of
      approximately 17%. The PMPM cost of the covered pharmacotherapy was approximately
      0.13 dollars. CONCLUSIONS: The cost to employers of providing insurance coverage
      for smoking-cessation pharmacotherapy to their employees is low. By informing
      insurance purchasing decisions, these results may facilitate the adoption of such
      coverage, with the goal of ultimately reducing the proportion of employees who
      smoke.

PMID- 17196786
TI  - Evidence for the absorption of heparin by rat stomach.
AB  - Antithrombotic activity and heparin with endothelium are observed in rats when
      heparin is administered by the oral route. Peak endothelial concentrations at 6
      min suggest rapid absorption. To identify the site of absorption, stomach and
      duodenum were isolated by tying the pyloric sphincter of male Wistar rats and
      heparin (unfractionated bovine lung, 60 mg/kg) was administered by stomach tube
      or injected into the duodenum. Heparin in plasma and aortic endothelium,
      collected within 15 min, was determined by densitometry following agarose gel
      electrophoresis with toluidine blue staining. Heparin was recovered in 5 of 10
      endothelial (0.136+/-0.068 microg/cm(2)) and 6 of 10 plasma (0.06+/-0.02
      microg/ml) samples when administered in the stomach and in 0 of 9 endothelial and
      2 of 9 plasma (0.02+/-0.02 microg/ml) samples when injected into the duodenum. To
      further study heparin distribution, stomach layers were separated and analysed 15
      min and 4h following heparin administration by stomach tube. Heparin was
      recovered in muscle and mucosal layers as well as washes indicating that heparin
      passes through stomach tissue. Heparin was also recovered from the portal vein,
      endothelium and lung. These results indicate that heparin is absorbed following
      oral administration and that the stomach is an important site of absorption.

PMID- 17196787
TI  - Succimer chelation normalizes reactivity to reward omission and errors in lead
      exposed rats.
AB  - This study evaluated the efficacy of a 3-week course of succimer treatment to
      alleviate behavioral deficits in rats exposed to lead (Pb) for the first 4 weeks
      of life. A 3 x 2 factorial design was used: three levels of lead exposure (No Pb,
      Moderate, and High Pb) and two levels of chelation (succimer or vehicle).
      Behavioral testing was conducted following chelation therapy, from 2 to 9 months
      of age; this report presents the results of two of the administered tasks: (1) a
      conditional olfactory discrimination task (baseline task), and (2) a conditional
      olfactory discrimination task with periodic reward omission on some correct
      trials (RO task). In the RO task, the performance disruption produced by
      committing an error on the previous trial was significantly greater for both
      unchelated lead-exposed groups than for controls. The High Pb rats were also more
      sensitive to reward omission than controls, providing converging evidence for
      impaired regulation of arousal or emotion. Importantly, succimer treatment was
      effective in normalizing the heightened reactivity of the lead-exposed animals to
      both errors and reward omission. In addition, non-lead-exposed rats that were
      treated with succimer tended to be more affected by a prior error than controls
      in their latency to respond on post-error trials. In sum, these findings provide
      new evidence that succimer chelation can significantly lessen the lasting
      neurobehavioral dysfunction produced by early lead exposure, but also suggest
      that there may be risks of administering the drug to individuals without elevated
      blood lead levels.

PMID- 17196788
TI  - P3 components and adolescent binge drinking in Southwest California Indians.
AB  - In adolescence, consuming a large number of drinks over a short interval of time
      (e.g. binging) is not an uncommon occurrence. Since adolescence is an important
      neurodevelopmental period, the effect of binge drinking on brain and behavior has
      become a significant health concern. The present study evaluated event-related
      potentials (ERPs) in young adult Southwest California Indians who had a history
      of binge drinking during their adolescence. One hundred twenty five participants
      who were currently 18-25 yrs of age who were free of Axis I psychiatric diagnoses
      were categorized as: 1) reporting no binge drinking during adolescence (>5 drinks
      per occasion before age 18) or drug dependence diagnoses 2) reporting binge
      drinking during adolescence with no drug dependence diagnoses 3) reporting binge
      drinking during adolescence and drug dependence diagnoses. ERPs were collected
      using a facial discrimination task. Adolescent alcohol and drug exposure was
      found to be associated with decreases in the latency of an early P3 component
      (P350). Decreases in a later component amplitude (P450) were also found in young
      adults exposed to alcohol, and those exposed to alcohol and drugs. However, that
      finding appears to be a combined result of predisposing factors such as family
      history of alcoholism and presence of other externalizing diagnoses. Taken
      together these preliminary studies suggests that adolescent binge drinking may
      result in a decreases in P3 component latencies and amplitudes perhaps reflecting
      a loss or delay in the development of inhibitory brain systems.

PMID- 17196790
TI  - MRI intensity nonuniformity correction using simultaneously spatial and gray
      level histogram information.
AB  - A novel approach for correcting intensity nonuniformity in magnetic resonance
      imaging (MRI) is presented. This approach is based on the simultaneous use of
      spatial and gray-level histogram information. Spatial information about intensity
      nonuniformity is obtained using cubic B-spline smoothing. Gray-level histogram
      information of the image corrupted by intensity nonuniformity is exploited from a
      frequential point of view. The proposed correction method is illustrated using
      both physical phantom and human brain images. The results are consistent with
      theoretical prediction, and demonstrate a new way of dealing with intensity
      nonuniformity problems. They are all the more significant as the ground truth on
      intensity nonuniformity is unknown in clinical images.

PMID- 17196789
TI  - 1H MRS-detectable metabolic brain changes and reduced impulsive behavior in adult
      rats exposed to methylphenidate during adolescence.
AB  - Administration of methylphenidate (MPH, Ritalin) to children affected by
      attention deficit hyperactivity disorder (ADHD) is an elective therapy, which
      however raises concerns for public health, due to possible persistent neuro
      behavioral alterations. We investigated potential long-term consequences at
      adulthood of MPH exposure during adolescence, by means of behavioral and brain
      MRS assessment in drug-free state. Wistar adolescent rats (30- to 44-day-old)
      were treated with MPH (0 or 2 mg/kg once/day for 14 days) and then left
      undisturbed until adulthood. Levels of impulsive behavior were assessed in the
      intolerance-to-delay task: Food-restricted rats were tested in operant chambers
      with two nose-poking holes, delivering one food pellet immediately, or five
      pellets after a delay whose length was increased over days. MPH-exposed animals
      showed a less marked shifting profile from the large/late to the small/soon
      reward, suggesting reduced basal levels of impulsivity, compared to controls. In
      vivo MRI-guided 1H MRS examinations at 4.7 T in anaesthetised animals revealed
      long-term biochemical changes in the dorsal striatum (STR), nucleus accumbens
      (NAcc), and prefrontal cortex (PFC) of MPH-exposed rats. Notably, total creatine
      and taurine, metabolites respectively involved in bioenergetics and synaptic
      efficiency, were up-regulated in the STR and conversely down-regulated in the
      NAcc of MPH-exposed rats. A strong correlation was evident between non
      phosphorylated creatine in the STR and behavioral impulsivity. Moreover,
      unaltered total creatine and increased phospho-creatine/creatine ratio were
      detected in the PFC, suggesting improved cortical energetic performance. Because
      of this enduring rearrangement in the forebrain function, MPH-exposed animals may
      be more efficient when faced with delay of reinforcement. In summary, MPH
      exposure during adolescence produced enduring MRS-detectable biochemical
      modifications in brain reward-related circuits, which may account for increased
      self-control capacity of adult rats.

PMID- 17196791
TI  - P38 and ERK mitogen-activated protein kinases mediate acrolein-induced apoptosis
      in Chinese hamster ovary cells.
AB  - Acrolein, which is a highly reactive alpha,beta-unsaturated aldehyde generated by
      lipid peroxidation, can affect cells and tissues and cause various disorders.
      Increased levels of unsaturated aldehydes play an important role in the
      pathogenesis of a number of human diseases such as Alzheimer's disease,
      atherosclerosis and diabetes. Acrolein is a highly ubiquitous toxic environmental
      pollutant. Because of human exposure, there is a need for investigating the
      mechanisms involved in acrolein toxicity at the cellular and molecular levels.
      Acrolein can induce cell death by apoptosis, although the mechanisms are not
      entirely clear. The present study investigates whether mitogen-activated protein
      kinases (MAPKs) play a role in activation of apoptosis by acrolein. Our findings
      show that acrolein-mediated apoptosis is in fact MAPK-dependent in Chinese
      hamster ovary cells. The MAP family kinases, including ERK and p38 kinase, and
      the transcription factor c-Jun were all activated by phosphorylation after 1 h
      exposure to acrolein. Phosphorylation of ERK and p38 kinases and their blockade
      by an ERK inhibitor, U0126, or a p38 inhibitor, SB203580, respectively, suggested
      that activation of apoptosis by acrolein is ERK- and p38-dependent. Thus,
      blockade of ERK and p38 inhibited chromatin condensation, caspase-7 and -9
      activation as well as ICAD cleavage induced by acrolein. JNK and AKT kinases seem
      to be implicated in survival pathways against acrolein insult, since their
      respective inhibitors, SP600125 and LY294002/Wortmannin switched the mode of cell
      death from apoptosis to total necrosis. Finally, acrolein induced phosphorylation
      of the pro-apoptotic factor p53 which is responsible for transcription of pro
      apoptotic factors such as Bax and Fas ligand. These results provide new
      information demonstrating the implication of MAPKs and AKT in acrolein-induced
      apoptosis, and this information may be useful for understanding the pathogenesis
      of a number of tissue diseases and environmental toxicity in response to
      acrolein.

PMID- 17196792
TI  - RIG1 suppresses Ras activation and induces cellular apoptosis at the Golgi
      apparatus.
AB  - Retinoid-inducible gene 1 encodes RIG1 is a growth regulator, which inhibits the
      pathways of the RAS/mitogen-activated protein kinases by suppressing the
      activation of RAS. Confocal microscopic analysis demonstrated that RIG1 is
      localized in the endoplasmic reticulum (ER) and Golgi apparatus in HtTA cervical
      cancer cells. Carboxyterminal-deleted RIG1 targeted to the Golgi or ER was
      constructed and validated. The activation of HRAS was inhibited by 25.1% or 81.4%
      in cells cotransfected with wild-type or Golgi-targeted RIG1, respectively.
      Expression of wild-type or Golgi-targeted RIG1 for 24 h induced cellular
      apoptosis in HtTA cells, as assessed by MTT assay, the release of lactate
      dehydrogenase, and chromatin condensation. In contrast, ER-targeted RIG1 and
      carboxyterminal-deleted RIG1 (RIG1DeltaC) exhibited no activity. Caspase-2, -3,
      and -9 were activated following the expression of wild-type and Golgi-targeted
      RIG1. Although the caspase-3 inhibitor Z-DEVD-FMK partially or completely
      reversed the cell death induced by wild-type or Golgi-targeted RIG1, it did not
      prevent the anti-RAS effect of RIG1. In conclusion, the proapoptotic and anti-RAS
      activities of RIG1 are primarily associated with the Golgi localization of the
      protein. The proapoptotic activities of RIG1 are mediated through the activation
      of caspase-2 and -3 and are independent of its effect on RAS.

PMID- 17196793
TI  - Dose-response population analysis of levetiracetam add-on treatment in refractory
      epileptic patients with partial onset seizures.
AB  - In this post hoc analysis, individual seizure counts from four double-blind
      trials of adjunctive treatment with levetiracetam were analyzed by non-linear
      mixed-effects modeling (NONMEM). First, a model was fitted to the individual
      count data assuming a Poisson distribution, in order to classify the patients as
      either improving or deteriorating from baseline. In the second stage, the dose
      response relationship in improving patients was determined by fitting the data to
      an E(max) model including a placebo effect. The percentage of improvers was 59%
      on placebo and 73%, 74%, 77% and 73% on levetiracetam 1, 2, 3 and 4g/day,
      respectively. The ED(50) of 1408mg/day was close to the current WHO Defined Daily
      Dose of levetiracetam (1500mg). The maximum recommended dose of 3000mg/day was
      predicted to reduce seizures by >or=90% in 10% of improving patients. Age,
      gender, body weight, race, and number of concomitant antiepileptic drugs neither
      affected the percentage of responders nor the extent of change in seizure
      frequency from baseline.

PMID- 17196794
TI  - Influence of instruction on the Japanese Verbal Learning Test in patients with
      schizophrenia.

PMID- 17196795
TI  - Response to SSRIs and role of the hormonal therapy in post-menopausal depression.
AB  - The aim of this study is to prospectively evaluate the antidepressant response to
      SSRIs in depressed post-menopausal women with or without hormonal therapy (HT),
      and to analyze the possible influence of basal serum levels of gonadotropins and
      sexual hormones on the antidepressant response. 170 post-menopausal women with a
      depressive episode (DSM-IV criteria)--47 on HT and 123 not on HT--started the
      treatment with an SSRI. Depressive symptoms were assessed at baseline and 7 weeks
      thereafter by raters blind to treatment regimen. Response rates were 63.2% in the
      group without HT and 83.7% in the HT group (p=0.013). An inverse correlation
      emerged between the basal levels of LH and the improvement in HRSD scores
      (p=0.001) in the group without HT. In conclusion, HT appeared to improve the
      antidepressant response to SSRIs. Furthermore, in post-menopausal women, LH basal
      levels may be taken into account as possible predictor of response.

PMID- 17196797
TI  - Notch signaling reveals developmental plasticity of Pax4(+) pancreatic endocrine
      progenitors and shunts them to a duct fate.
AB  - Relatively little is known about the developmental signals that specify the types
      and numbers of pancreatic cells. Previous studies suggested that Notch signaling
      in the pancreas inhibits differentiation and promotes the maintenance of
      progenitor cells, but it remains unclear whether Notch also controls cell fate
      choices as it does in other tissues. To study the impact of Notch in progenitors
      of the beta cell lineage, we generated mice that express Cre-recombinase under
      control of the Pax4 promoter. Lineage analysis of Pax4(+) cells demonstrates they
      are specified endocrine progenitors that contribute equally to four islet cell
      fates, contrary to expectations raised by the dispensable role of Pax4 in the
      specification of the alpha and PP subtypes. In addition, we show that activation
      of Notch in Pax4(+) progenitors inhibits their differentiation into alpha and
      beta endocrine cells and shunts them instead toward a duct fate. These
      observations reveal an unappreciated degree of developmental plasticity among
      early endocrine progenitors and raise the possibility that a bipotent duct
      endocrine progenitor exists during development. Furthermore, the redirection of
      Pax4(+) cells from alpha and beta endocrine fates toward a duct cell type
      suggests a positive role for Notch signaling in duct specification and is
      consistent with the more widely defined role for Notch in cell fate
      determination.

PMID- 17196796
TI  - Known maternal gradients are not sufficient for the establishment of gap domains
      in Drosophila melanogaster.
AB  - Gap genes are among the first transcriptional targets of maternal morphogen
      gradients in the early Drosophila embryo. However, it remains unclear whether
      these gradients are indeed sufficient to establish the boundaries of localized
      gap gene expression patterns. In this study, we address this question using gap
      gene circuits, which are data-driven mathematical tools for extracting regulatory
      information from quantitative wild-type gene expression data. We present new,
      quantitative data on the mRNA expression patterns for the gap genes Kruppel (Kr),
      knirps (kni) and giant (gt) during the early blastoderm stage of Drosophila
      development. This data set shows significant differences in timing of gap gene
      expression compared to previous observations, and reveals that early gap gene
      expression is highly variable in both space and time. Gene circuit models fit to
      this data set were used for a detailed regulatory analysis of early gap gene
      expression. Our analysis shows that the proper balance of maternal repression and
      activation is essential for the correct positioning of gap domains, and that such
      balance can only be achieved for early expression of kni. In contrast, our
      results suggest that early expression of gt requires local neutralization of
      repressive input in the anterior region of the embryo, and that known maternal
      gradients are completely insufficient to position the boundaries of the early
      central Kr domain, or in fact any Kr-like domain in the central region of the
      blastoderm embryo. Based on this, we propose that unknown additional regulators
      must be involved in early gap gene regulation.

PMID- 17196798
TI  - Al coordination and water speciation in hydrous aluminosilicate glasses: direct
      evidence from high-resolution heteronuclear 1H-27Al correlation NMR.
AB  - In order to shed light on the dissolution mechanisms of water in depolymerized
      aluminosilicate melts/glasses, a comprehensive one- (1D) and two-dimensional (2D)
      NMR study has been carried out on hydrous Ca- and Mg-aluminosilicate glasses of a
      haplobasaltic composition. The applied techniques include 1D 1H MAS NMR and 27Al-
      >1H cross-polarization (CP) MAS NMR, and 2D 1H NOESY and double-quantum (DQ) MAS
      NMR, 27Al triple-quantum (3Q) MAS NMR and 27Al-->1H heteronuclear correlation
      (HETCOR) and 3QMAS/HETCOR NMR. Ab initio calculations were also performed to
      place additional constraints on the 1H NMR characteristics of AlOH and Si(OH)Al
      groups. This study has revealed, for the first time, the presence of free OH
      (i.e. (Ca, Mg)OH), SiOH and AlOH species, in addition to molecular H2O, in
      hydrous glasses of a depolymerized aluminosilicate composition. The AlOH groups
      are mostly associated with four-coordinate Al, but some are associated with five-
      and six-coordinate Al.

PMID- 17196799
TI  - Impact of initiators in preparing magnetic polymer particles by miniemulsion
      polymerization.
AB  - Sub-micron sized polystyrene particles containing magnetite more than 30 wt.%
      were prepared by miniemulsion polymerization with commercially available
      ferricolloid. The effects of some water-soluble initiators and/or oil-soluble
      initiators on the particles characteristics, such as the size, morphology,
      magnetic properties and colloidal stability, were studied. The size of monomer
      droplets/polymer particles increased from 60 to 300 nm during polymerization,
      keeping magnetic in core when potassium persulfate (KPS) or ammonium persulfate
      (APS) was used as the sole initiator. These particles were easily separated from
      the medium within short time scale in external magnetic field, while such
      characteristics were controlled by the amount of persulfate used for the
      polymerization. In contrast, when 2,2'-azobis isobutyronitrile (AIBN) was used as
      the initiator, the size of droplets/particles was retained to be 90 nm at the
      most and magnetite nanoparticles located at the surface of polystyrene particles,
      which were so colloidally stable that they were not separated in external
      magnetic field. The above-mentioned effect of initiators on particle size in
      persulfate system was likely originated from the decrease of pH value and the
      increase of ionic strength, which induced the fusion of droplets/particles
      containing magnetite. Mixed-initiators system resulted in intermediate
      characteristics, compared with each initiator system. The location of magnetite
      in the particle seems to depend on where initiation/polymerization occurred in
      each initiator system.

PMID- 17196800
TI  - Microscopic observation and characterization of the oil bridge between dehulled
      roasted sesame seeds.
AB  - The formation of an oil bridge between adhesive seeds was observed
      microscopically. The geometry of the oil bridge was affected by the shape of the
      adhesive seeds. The capillary force of the oil bridge was estimated from the
      image captured by the microscope. The average capillary force was 127 microN,
      which was five times higher than the average gravity of the seeds. It was
      observed that several oil bridges formed between two seeds. These results
      indicated an adequate ability of the seeds to adhere. The capillary force of the
      oil bridge increased with surface oil content. The probability of formation of an
      oil bridge increased with surface oil content when the surface oil content was
      above 0.63%. The probability of formation of an oil bridge markedly increased
      when sucrose was added to the seeds.

PMID- 17196801
TI  - Liquid-liquid equilibria of polyrotaxane and poly(vinyl alcohol).
AB  - Liquid-liquid equillibria (LLE) of the tertiary system of hydroxypropylated
      polyrotaxane (HPPR)-poly(vinyl alcohol) (PVA)-solvent have been investigated by
      focusing on the internal structures of HPPR-PVA blend gels. The phase diagrams of
      the HPPR-PVA aqueous systems displayed two liquid phases at a high concentration
      and molecular weight of PVA. This result was consistent with the prediction of
      the Flory-Huggins lattice model. On the contrary, the HPPR-PVA-DMSO system
      exhibited only a single phase. The HPPR-PVA blend gels crosslinked in
      dimethylsulfoxide (DMSO) were highly transparent over a wide concentration range,
      while the gels prepared in water were opaque at high polymer concentrations.
      Spherical domains were observed in the opaque gels by laser scanning confocal
      microscopy, and the sizes of the domains were significantly dependent on the
      amount of cross-linking reagent utilized. These results indicated that the
      transparency of the HPPR-PVA blend gels was strongly affected by the competition
      between the liquid-liquid two-phase separation and the crosslinking HPPR and PVA
      polymers during the preparation of the blend gels.

PMID- 17196802
TI  - Preliminary studies of the physical stability of a glucagon-like peptide-1
      derivate in the presence of metal ions.
AB  - The physical stability and the secondary structure of a glucagon-like peptide-1
      derivative were investigated in the presence of the metal ions Al(3+), Zn(2+),
      Mg(2+), and K(+), known as possible leachables from container-closure systems.
      Metal ions were investigated in concentrations of 0-50 ppm. Test solutions of the
      peptide were exposed to elevated temperature (25 degrees C) and rotation (37
      degrees C) for up to 4 weeks. The samples were examined by nephelometry,
      thioflavine T fluorescence, and Fourier-transform infrared spectroscopy. Readily
      prepared test solutions were examined by tryptophan fluorescence. The stability
      profiles were unchanged after addition of Mg(2+) and K(+) in 0-50 ppm
      concentrations. However, a concentration-dependent increase in thioflavine
      intensities was observed after addition of Al(3+) and Zn(2+). The destabilising
      effect of Al(3+) and Zn(2+) was furthermore confirmed by FTIR as the secondary
      structure of the peptide changed from predominantly alpha-helix to a higher beta
      sheet content. Additionally Al(3+) changed the secondary structure of the peptide
      using Trp fluorescence.

PMID- 17196803
TI  - A review of the formation and classification of amphiphilic block copolymer
      nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes.
AB  - Amphiphilic block copolymers are able to form a range of different
      nanoparticulate structures. These include micelles, nanospheres, nanocapsules,
      and polymersomes. This review attempts to clarify some of the terminology used in
      the literature by providing an overview of the major features of each type of
      nanoparticle and the factors that influence the formation of particular
      nanoparticulate formulations.

PMID- 17196804
TI  - Single-layer transdermal film containing lidocaine: modulation of drug release.
AB  - We have recently described an innovative drug delivery system, a water-based and
      vapor permeable film intended for dermal and/or transdermal delivery. The aim of
      this work was to modulate the delivery of the model drug lidocaine hydrochloride
      from the transdermal film across rabbit ear skin. The effect of drug loading, of
      film-forming polymer type and content, of adhesive and plasticizer on lidocaine
      transport across the skin was evaluated. Additional objective was to evaluate the
      effect of occlusion on the kinetics of lidocaine transport, by applying an
      occlusive backing on the surface of the transdermal film. From the data obtained
      it can be concluded that the transdermal film acts as a matrix controlling drug
      delivery. The film-forming polymer molecular weight had a negligible effect on
      drug penetration, while its content was more effective. The choice of the
      adhesive seems to be the most important variable governing drug transport. In
      particular, the presence of lauric acid combined with a basic drug, such as
      lidocaine, can produce a relevant improvement in permeation, because of the
      formation of an ion pair. Concerning the kinetics, drug depletion is responsible
      for the declining permeation rates observed in the late times of permeation.

PMID- 17196805
TI  - Synchronized and sustained release of multiple components in silymarin from
      erodible glyceryl monostearate matrix system.
AB  - Development of sustained delivery systems for herbal medicines was very difficult
      because of their complexity in composition. The concept of synchronized release
      from sustained release systems, which is characterized by release of multiple
      components in their original ratio that defines a herbal medicine, served as the
      basis for keeping the original pharmacological activity. In this study, erodible
      matrix systems based on glyceryl monostearate and polyethylene glycol 6000 or
      poloxamer 188 were prepared to perform strict control on synchronized release of
      the five active components of silymarin, i.e. taxifolin, silychrystin,
      silydianin, isosilybin and silybin. The matrix system was prepared by a melt
      fusion method. Synchronized release was achieved with high similarity factor f(2)
      values between each two of the five components. Erosion profiles of the matrix
      were in good correlation with release profiles of the five components, showing
      erosion-controlled release mechanisms. Through tuning some of the formulation
      variables, the system can be adjusted for synchronized and sustained release of
      silymarin for oral administration. In vitro hemolysis study indicated that the
      synchronized release samples showed a much better stabilizing effect on
      erythrocyte membrane.

PMID- 17196806
TI  - Poly(2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate, dibutyl maleate)
      membrane controlled clonidine zero-order release.
AB  - Poly(2-hydroxy-3-phenoxypropylacrylate, 4-hydroxybutyl acrylate, dibutyl maleate)
      membrane was synthesized by UV curing method in our laboratory for the first
      time. When above-mentioned monomers were in the weight ratio of 4:4:2, the
      membrane not only had perfect permeation property but also had excellent
      plasticity, so the membrane made from monomers in the ratio of 4:4:2 was chosen
      as an optimized membrane. The optimized membrane provided perfect linear
      permeation properties in clonidine transdermal drug delivery system. The
      permeation rate decreased in proportion to the thickness of membrane. When the
      concentrations of clonidine were in the range of 0.5-7.0mg/ml, the permeation
      rate was proportional to the square root of clonidine concentrations. The
      optimized membrane was characterized by FTIR, DSC and SEM.

PMID- 17196807
TI  - Preparation and characterization of a self-emulsifying pellet formulation.
AB  - The purpose of the current study is to investigate the feasibility of producing
      solid self-emulsifying pellets using the extrusion/spheronization technique.
      Pellets were made from a mixture of C18 partial glycerides, Solutol HS15 and
      microcrystalline cellulose. Pellets with good physical properties (size, shape,
      friability) and self-emulsifying properties were produced. The pellets were, in
      contrast to pellets lacking Solutol, able to transfer a lipophilic dye and a spin
      probe into the aqueous media. The release kinetics and the microenvironment of
      the pellets during the release process were assessed using electron spin
      resonance (ESR) spectroscopy. The ESR results showed that the hydrophobic spin
      probe was localized mainly in the lipid environment all over the release time.
      Furthermore, the formulation was capable of accelerating the release of the drug
      diazepam and achieving a diazepam concentration above its saturation solubility.
      In conclusion, spherical pellets with low friability and self-emulsifying
      properties can be produced by the standard extrusion/spheronization technique.
      The pellets are capable of transfering lipophilic compounds into the aqueous
      phase and have a high potential to increase the bioavailability of lipophilic
      drugs.

PMID- 17196808
TI  - Chitosan/starch fibers and their properties for drug controlled release.
AB  - Fibers of chitosan and starch, with salicylic acid (SA) as model drug
      incorporated in different concentrations, were obtained by spinning their
      solution through a viscose-type spinneret into a coagulating bath containing
      aqueous tripolyphosphate (TPP) and ethanol. Chemical, morphological and
      mechanical properties characterization was carried out, as well as the studies of
      the factors that influence the drug releasing from chitosan/starch fibers. These
      factors included the component ratio of chitosan and starch, the loaded amount of
      SA, the pH and the ionic strength of the release solution and others. The
      diameter of the fibers is around 15+/-3 microm. The best values of the tensile
      strength at 12.21 cN/tex and breaking elongation at 25.13% of blend fibers were
      obtained when the starch content was 30 wt%; the water-retention value (WRV) of
      blend fibers increased as the composition of starch was raised. The results of
      controlled release tests showed that the amount of SA released increased with an
      increase in the proportion of starch present in the fiber. Moreover, the release
      rate of drug decreased as the amount of drug loaded in the fiber increased, but
      the cumulative release amount is increasing. The chitosan/starch fibers were also
      sensitive to pH and ionic strength. The release rate was being accelerated by a
      lower pH and a higher ionic strength, respectively. All the results indicated
      that the chitosan/starch fiber was potentially useful in drug delivery systems.

PMID- 17196810
TI  - Ozone enhances the airway inflammation initiated by diesel exhaust.
AB  - Exposure to air pollution is associated with adverse health effects, with
      particulate matter (PM) and ozone (O(3)) both indicated to be of considerable
      importance. Diesel engine exhaust (DE) and O(3) generate substantial inflammatory
      effects in the airways. However, as yet it has not been determined whether a
      subsequent O(3) exposure would add to the diesel-induced airway inflammatory
      effects. Healthy subjects underwent two separate exposure series: A 1-h DE
      exposure at a PM-concentration of 300 microg/m(3), followed after 5h by a 2-h
      exposure to filtered air and 0.2 ppm O(3), respectively. Induced sputum was
      collected 18 h after the second exposure. A significant increase in the
      percentage of neutrophils (PMN) and concentration of myeloperoxidase (MPO) was
      seen in sputum post DE+O(3) vs. DE+air (p<0.05 and <0.05, respectively).
      Significant associations were observed between the responses in MPO concentration
      and total PMN cells (p=0.001), and also between MPO and matrix metalloproteinase
      9 (MMP-9) (p<0.001). The significant increase of PMN and MPO after the DE+O(3)
      exposures, compared to DE+air, denotes an O(3)-induced magnification of the DE
      induced inflammation. Furthermore, the correlation between responses in MPO and
      number of PMNs and MMP-9 illustrate that the PMNs are activated, resulting in a
      more potent inflammatory response. The present study indicates that O(3) exposure
      adds significantly to the inflammatory response that is established by diesel
      exhaust. This interaction between exposure to particulate pollution and O(3) in
      sequence should be taken into consideration when health effects of air pollution
      are considered.

PMID- 17196809
TI  - Assessment of physical and antioxidant activity stability, in vitro release and
      in vivo efficacy of formulations added with superoxide dismutase alone or in
      association with alpha-tocopherol.
AB  - A topical formulation was added with different concentrations of superoxide
      dismutase (SOD) alone or in association with alpha-tocopherol (alpha-TOC). The
      physical stability was evaluated by rheological behavior of formulations stored
      at 4 degrees C, 30 degrees C/60% RH and 40 degrees C/70% RH for 6 months. SOD
      alone and formulations containing SOD 0.2%, 0.4% or 0.6% or SOD and alpha-TOC
      were stored in the same conditions and the enzymatic activity was evaluated by
      the superoxide anion scavenging using chemiluminescence measurement. In vitro
      release study was carried out using modified Franz diffusion cell and SOD
      formulations photoprotection against skin erythema was observed for 72 h. SOD and
      alpha-TOC formulation proved to be instable, since the interaction between the
      antioxidants led to both physical and enzymatic activity instability. SOD
      formulations showed to be physically stable and maintained the enzymatic activity
      for 6 months when stored at 4 and 30 degrees C/60% RH. Despite the fact of low
      SOD release from the formulation, it was effective in inhibiting the UVB-induced
      skin erythema for 48 h after a single application. Topical administration of
      antioxidants provides an efficient way to enrich the endogenous cutaneous
      protection system, and SOD formulations could be used for improving
      photoprotection of skin.

PMID- 17196812
TI  - Influence of aeration rate and biodegradability fractionation on composting
      kinetics.
AB  - The influences of aeration rate and biodegradability fractionation on
      biodegradation kinetics during composting were studied. The first step was the
      design of a suitable lab-reactor that enabled the simulation of composting. The
      second step comprised of composting trials of six blends of sludge (originating
      from a food processing effluent) with wood chips using aeration rates of 1.69,
      3.62, 3.25, 8.48, 11.98 and 16.63 L/h/kg DM of mixture. Biodegradation was
      evaluated by respiration measurements and from the analysis of the substrate (dry
      matter, organic matter, total carbon and chemical oxygen demand removal).
      Continuous measurement of oxygen consumption was coupled with the analysis of
      initial substrate and composted product for chemical oxygen demand (in the
      soluble and non-soluble fractions), which enabled an evaluation of the organic
      matter biodegradability. Oxygen requirements to remove both the easily and slowly
      biodegradable fractions were determined. Dividing the substrate into different
      parts according to biodegradability allowed explanation of the influence of
      aeration rate on stabilization kinetics. Considering that the biodegradation
      kinetics were of the first-order, the kinetic constants of the easily and slowly
      biodegradable fractions were calculated as a function of temperature. The
      methodology presented here allows the comparison of organic wastes in terms of
      their content of easily and slowly biodegradable fractions and the respective
      biodegradation kinetics.

PMID- 17196811
TI  - Allergy in marathon runners and effect of Lactobacillus GG supplementation on
      allergic inflammatory markers.
AB  - OBJECTIVE: We studied the prevalence of asthma and allergy in non-elite marathon
      runners and investigated the effects of probiotic supplementation on allergic
      inflammatory markers. METHODS: Asthma and allergies were surveyed by
      questionnaire, and blood eosinophils, serum eosinophil cationic protein (ECP),
      total IgE, and Phadiatop were measured in 141 Finnish marathon runners who took
      part in the Helsinki City Marathon. They were also randomized to receive either
      Lactobacillus GG (LGG) or placebo during the 3 months of the pollen season prior
      to the marathon. RESULTS: Lifetime prevalence of physician-diagnosed asthma was
      4.3% (six out of 139 athletes), of allergic rhinitis 17.3% (24/139), of food
      allergy 5.0% (7/139), and of atopic eczema 4.3% (6/139). Prevalence of atopy was
      31% (35/112), and 21% (24/112) of the athletes were sensitized to birch pollen.
      Asthma or allergy medication was used by 20% (28/139) of the athletes. During
      pollen season, serum ECP increased significantly in all athletes, and total IgE
      and Phadiatop in atopics. The marathon induced a significant eosinopenia but had
      no effect on serum ECP or total IgE. No differences in changes were seen between
      groups receiving LGG or placebo. CONCLUSION: Non-elite marathon runners have
      asthma and allergies similar to Finnish general population. LGG supplementation
      did not prevent the increase of allergic markers during the pollen season, or the
      eosinopenia induced by the marathon.

PMID- 17196813
TI  - The molecular biology of cytoplasmically inherited male sterility and prospects
      for its engineering.
AB  - Nucleocytoplasmic male sterilities are binary genetic systems driven by
      mitochondrial, maternally inherited genes that induce male sterility and a female
      phenotype and which are overcome by nuclear restorers of fertility. They
      contribute to the reproductive biology and evolution of natural populations and
      are valuable tools for the commercial production of hybrid seeds in crops. For
      species with no natural form of cytoplasmic male sterility, such sterility can in
      some cases be introduced from different, but related, species through sexual
      crosses or somatic hybridisation. Somatic hybridisation is the only technique
      currently available for manipulating plant mitochondrial genomes. Recent
      successes in plastid transformation have opened up entirely new perspectives for
      the engineering of cytoplasmic male sterilities in transplastomic plants.

PMID- 17196814
TI  - Clinical hurdles for the transplantation of cardiomyocytes derived from human
      embryonic stem cells: role of molecular imaging.
AB  - Over the past few years, human embryonic stem cells (hESCs) have gained
      popularity as a potentially ideal cell candidate for tissue regeneration. In
      particular, hESCs are capable of cardiac lineage-specific differentiation and
      confer improvement of cardiac function following transplantation into animal
      models. Although such data are encouraging, there remain significant hurdles
      before safe and successful translation of hESC-based treatment into clinical
      therapy, including the ability to assess cells following transplant. To this end,
      molecular imaging has proven a reliable methodology for tracking the long-term
      fate of transplanted cells. Imaging reporter genes that are introduced into the
      cells before transplantation enable non-invasive and longitudinal studies of cell
      viability, location and behaviour in vivo. Therefore, molecular imaging is
      expected to play an increasing role in characterizing the biology and physiology
      of hESC-derived cardiac cells in living subjects.

PMID- 17196815
TI  - Polymorphisms of DNA repair genes are risk factors for prostate cancer.
AB  - DNA repair gene alterations have been shown to cause a reduction in DNA repair
      capacity. We hypothesised that DNA repair gene polymorphisms may be risk factors
      for prostate cancer (PC). To test this hypothesis, DNA samples from 165 cases of
      prostate cancer and healthy controls were analyzed by PCR-RFLP to determine the
      genotypic frequency of three DNA repair genes (XRCC1, XPC and XRCC7). We found
      that the frequency of 939Gln variant at XPC Lys939Gln was significantly lower in
      PC cases (OR=0.39, P=0.016). Haplotype analysis of XRCC1 Arg194Trp (C/T) and
      Arg399Gln (G/A) revealed that the frequency of the T-A haplotype was
      significantly higher in PC patients. This is the first report on the studies of
      XPC and XRCC1 Arg194Trp polymorphisms in PC, and our present data suggest that
      XPC Lys939Gln and the T-A haplotype of XRCC1 Arg194Trp and Arg399Gln may be risk
      factors for PC in Japanese.

PMID- 17196816
TI  - Biological oxidation of elemental sulphur added to three composts from different
      feedstocks to reduce their pH for horticultural purposes.
AB  - The biological oxidation of elemental sulphur (S(o)) added to three alkaline
      composts prepared with a range of organic wastes (CC, melon crop residues; MC,
      mixed manures; and BC, pine bark) to reduce their pH was studied. The titration
      curves showed that to achieve an equivalent pH drop, compost CC needed a larger
      dose of S(o) than did composts MC and BC. The acidification efficiency was high
      in the three composts (53%), but the pH reduction obtained from the titration
      curves in MC and BC composts was lower than expected. S(o) oxidation in amended
      composts was found to be related to pH and CaCO(3) content decreases, and to the
      rise in CaSO(4) and electrical conductivity levels. A remarkable increase in the
      autotrophic bacteria population and a slight increase in heterotrophic bacteria
      along with S(o) oxidation were recorded. Actinomycetes, fungi and yeasts were not
      affected by the addition of S(o) to composts.

PMID- 17196817
TI  - Evaluation of thermally modified Grevillea robusta heartwood as an alternative to
      shortage of wood resource in Kenya: Characterisation of physicochemical
      properties and improvement of bio-resistance.
AB  - Heat treatment of Grevillea robusta, a tropical wood species of low natural
      durability, was carried-out under inert conditions to improve its decay
      resistance. Resistance of heat treated samples was evaluated by malt agar block
      tests after three months of exposure to several wood rotting fungi. Also
      resistance of heat treated wood against termites was tested in the laboratory and
      in the field. Results showed that durability against fungi and termites was
      greatly improved after treatment. There was a good correlation between decay
      resistance and mass loss due to thermal treatment. Microscopic, FTIR and (13)C
      MAS NMR analysis were performed to characterize wood chemical and anatomical
      modifications that occur after treatment to understand the reasons of the
      durability improvement.

PMID- 17196819
TI  - Striatal dopamine denervation and sensory integration for balance in middle-aged
      and older adults.
AB  - The dopaminergic system of the basal ganglia has been implicated in the
      integration of sensory information important for balance based on studies in
      patients with Parkinson's disease. Striatal dopaminergic activity decreases with
      normal aging. OBJECTIVE: To investigate the relationship between regional
      striatal dopaminergic denervation and sensory information integration important
      for balance in middle-aged and older adults. METHODS: Community-dwelling subjects
      (N=35; age 41-83) with no clinical diagnoses of conditions affecting balance
      underwent dynamic posturography testing (Sensory Organization Test/SOT) and C-11
      beta-CFT dopamine transporter positron emission tomography. RESULTS: Reduced
      ventral striatal dopamine was significantly correlated with increased anterior
      posterior sway in three SOT conditions. Specifically, during quiet standing (SOT
      Conditions #1, 2) and when repeatedly to sway-referenced visual environments (SOT
      Condition #3, Trial #3), pre-synaptic dopaminergic denervation in the
      anteroventral striatum explained over 20-25% of the variability in sway magnitude
      above and beyond that explained by age (p<or=0.01). Striatal dopaminergic
      denervation did not impact balance in sway-referenced floor conditions.
      CONCLUSIONS: The SOT Condition #3 findings suggest that, in normal aging, the
      central ability to inhibit balance destabilizing vision-related postural control
      processes depends at least partially on striatal dopaminergic pathways. In
      contrast, striatal dopaminergic denervation does not appear to impair the ability
      to disengage destabilizing proprioceptive inputs and to trigger the vestibular
      control system during challenging sensory perturbations (SOT Conditions #4-6).
      Finally, quiet standing results (SOT Conditions #1, 2) justify the need to
      further investigate the impact of striatal dopaminergic denervation on the
      ability to tune muscle tone in healthy adults.

PMID- 17196818
TI  - Bicyclic carbamates as inhibitors of papain-like cathepsin proteases.
AB  - A 6-oxa-1-aza-bicyclo[3.2.1]octan-7-one system inhibits the proteolytic activity
      of several cysteine proteases belonging to the papain family. In vitro
      mechanistic studies and in silico calculations suggest that the minimal pi
      overlap between the bridgehead nitrogen and the carbonyl leads to a considerable
      weakening of the urethane system, making it susceptible to nucleophilic attack
      from the active site thiol group. The resulting covalent adduct is slowly
      hydrolyzed, releasing the hydroxypiperidine product of the inhibitor. Synthesis
      and testing of a set of analogs led to variable protease subtype selectivities
      ranging from micromolar to nanomolar potencies.

PMID- 17196820
TI  - Activation of PKR: an open and shut case?
AB  - The double-stranded (ds) RNA-activated protein kinase, PKR, has a key role in the
      innate immunity response to viral infection in higher eukaryotes. PKR contains an
      N-terminal dsRNA-binding domain and a C-terminal kinase domain. In the prevalent
      autoinhibition model for PKR activation, dsRNA binding induces a conformational
      change that leads to the release of the dsRNA-binding domain from the kinase,
      thus relieving the inhibition of the latent enzyme. Structural and biophysical
      data now favor a model whereby dsRNA principally functions to induce dimerization
      of PKR via the kinase domain. This dimerization model has implications for other
      PKR regulatory mechanisms and represents a new structural paradigm for control of
      protein kinase activity.

PMID- 17196821
TI  - Knee arthrodesis with navigation: a new indication for computer-assisted surgery?
      A case report.
AB  - We describe a case of navigation-aided knee arthrodesis in a patient with a
      previous femoral deformity. Because of the complex deformity and the foreseeable
      difficulties in obtaining correct limb mechanical axis, a wireless navigation
      system was used to perform cuts of the distal femur and proximal tibia in both
      the coronal and sagittal planes. For a stable arthrodesis two monolateral
      external fixation devices were used. Twenty months after the procedure the
      patient did not have pain and walked without the aid of walking sticks. The final
      mechanical axis was 180 degrees.

PMID- 17196822
TI  - Typical and atypical carcinoid tumours: analysis of the experience of the Spanish
      Multi-centric Study of Neuroendocrine Tumours of the Lung.
AB  - BACKGROUND: This study examines the experience of the Spanish Multi-centric Study
      of Neuroendocrine Tumours of the Lung with patients treated surgically for
      typical and atypical carcinoid tumours. METHODS: From 1980 to 2002, 661 patients
      were treated surgically for 569 typical carcinoid tumours and 92 atypical
      carcinoid tumours. Three hundred and four cases were studied retrospectively from
      1980 to 1997 (261 typical carcinoid and 43 atypical carcinoid tumours); the other
      357 new cases (308 typical carcinoid and 49 atypical carcinoid tumours) were
      collected prospectively from 1998 to 2002. Tumours were classified according the
      1999 classification from the WHO and the International Association for the Study
      of Lung Cancer (IASLC). Several variables were reviewed in all patients.
      Univariate and multivariate statistical analyses were performed in order to
      determine whether clinical characteristics were associated with significant
      differences in survival. RESULTS: In the total of the patients, 5-year survival
      for different tumours was as follows: typical carcinoid: overall survival 97%;
      with nodal involvement 100%; atypical carcinoid: overall 78%; with nodal
      involvement 60%. A significant difference in survival was found between patients
      in the retrospective and prospective groups with atypical carcinoid and nodal
      involvement. The comparative analysis of several factors in typical and atypical
      carcinoid tumours showed a significant difference for mean age, tumour size,
      nodal involvement and distant metastases. CONCLUSION: Nodal involvement and
      histological sub-type appear as the most important factors influencing the
      prognosis. Adequate lung resection and systematic radical mediastinal
      lymphadenectomy should always be performed. Sleeve resection could be performed
      in central typical and atypical carcinoid tumours, avoiding pneumonectomy.

PMID- 17196824
TI  - Non-developmentally programmed cell death in Caenorhabditis elegans.
AB  - The simple nematode worm Caenorhabditis elegans has played a pivotal role in
      deciphering the molecular mechanisms of apoptosis. Precisely 131 somatic cells
      undergo programmed apoptotic death during development to contour the 959-cell
      adult organism. In addition to developmental cell death, specific genetic
      manipulations and extrinsic factors can trigger non-programmed cell death that is
      morphologically and mechanistically distinct from apoptosis. Here, we survey
      paradigms of cell death that is not developmentally programmed in C. elegans and
      review the molecular mechanisms involved. Furthermore, we consider the potential
      of the nematode as a platform to investigate pathological cell death. The
      striking extent of conservation between apoptotic pathways in worms and higher
      organisms including humans, holds promise that similarly, studies of non
      programmed cell death in C. elegans will yield significant new insights, highly
      relevant to human pathology.

PMID- 17196823
TI  - The essential oil of bergamot enhances the levels of amino acid neurotransmitters
      in the hippocampus of rat: implication of monoterpene hydrocarbons.
AB  - The effects of bergamot essential oil (BEO) on the release of amino acid
      neurotransmitters in rat hippocampus have been studied by in vivo microdialysis
      and by in vitro superfusion of isolated nerve terminals. Intraperitoneal
      administration of BEO (100microl/kg) significantly elevated the extracellular
      concentration of aspartate, glycine and taurine in a Ca(2+)-dependent manner. A
      dose-relation study generated a bell-shaped curve. When perfused into the
      hippocampus via the dialysis probe (20microl/20min), BEO produced a significant
      increase of extracellular aspartate, glycine, taurine as well as of GABA and
      glutamate. The augmentation of all amino acids was Ca(2+)-independent. Focally
      injected 1:1 diluted BEO preferentially caused extracellular increase of
      glutamate. Interestingly, this release appeared to be strictly Ca(2+)-dependent.
      BEO concentration-dependently enhanced the release of [(3)H]D-aspartate from
      superfused hippocampal synaptosomes. Similar results were obtained by monitoring
      the BEO-evoked release of endogenous glutamate. At relatively high
      concentrations, the BEO-induced [(3)H]d-aspartate release was almost entirely
      prevented by the glutamate transporter blocker dl-threo-beta-benzyloxyaspartic
      acid (DL-TBOA) and was Ca(2+)-independent. At relatively low concentrations the
      release of [(3)H]D-aspartate was only in part ( approximately 50%) DL-TBOA
      sensitive and Ca(2+)-independent; the remaining portion of release was dependent
      on extracellular Ca(2+). Interestingly, the monoterpene hydrocarbon-free fraction
      of the essential oil appeared to be inactive while the bergapten-free fraction
      superimposed the releasing effect of BEO supporting the deduction that psoralens
      may not be implicated. To conclude, BEO contains into its volatile fraction still
      unidentified monoterpene hydrocarbons able to stimulate glutamate release by
      transporter reversal and/or by exocytosis, depending on the dose administered.

PMID- 17196826
TI  - Neuromuscular adaptation in experimental and clinical neck pain.
AB  - The purpose of this brief review is to present evidence from experimental and
      clinical neck pain studies of pain-induced neuromuscular adaptations. It has been
      shown that clinical neck pain is associated with a substantial reorganization in
      the control strategies of cervical muscles during static and dynamic tasks.
      Experimental neck pain models allow local elicitation of nociceptive afferents,
      mimicking the sensory aspects of clinical pain, without major changes in muscle
      properties. These models may help understand the physiological mechanisms
      underlying the observations from clinical neck pain studies. The knowledge
      obtained from the interpretation of clinical findings with experimental pain
      models has relevance for the development of therapeutic interventions for the
      rehabilitation of patients with neck pain disorders.

PMID- 17196825
TI  - Biomechanical characteristics of elderly individuals walking on land and in
      water.
AB  - In this study, we examined Spatial-temporal gait stride parameters, lower
      extremity joint angles, ground reaction forces (GRF) components, and
      electromyographic activation patterns of 10 healthy elderly individuals (70+/-6
      years) walking in water and on land and compared them to a reference group of 10
      younger adults (29+/-6 years). They all walked at self-selected comfortable
      speeds both on land and while immersed in water at the Xiphoid process level.
      Concerning the elderly individuals, the main significant differences observed
      were that they presented shorter stride length, slower speed, lower GRF values,
      higher horizontal impulses, smaller knee range of motion, lower ankle
      dorsiflexion, and more knee flexion at the stride's initial contact in water than
      on land. Concerning the comparison between elderly individuals and adults,
      elderly individuals walked significantly slower on land than adults but both
      groups presented the same speed walking in water. In water, elderly individuals
      presented significantly shorter stride length, lower stride duration, and higher
      stance period duration than younger adults. That is, elderly individuals'
      adaptations to walking in water differ from those in the younger age group. This
      fact should be considered when prescribing rehabilitation or fitness programs for
      these populations.

PMID- 17196827
TI  - Torso flexion modulates stiffness and reflex response.
AB  - Neuromuscular factors that contribute to spinal stability include trunk stiffness
      from passive and active tissues as well as active feedback from reflex response
      in the paraspinal muscles. Trunk flexion postures are a recognized risk factor
      for occupational low-back pain and may influence these stabilizing control
      factors. Sixteen healthy adult subjects participated in an experiment to record
      trunk stiffness and paraspinal muscle reflex gain during voluntary isometric
      trunk extension exertions. The protocol was designed to achieve trunk flexion
      without concomitant influences of external gravitational moment, i.e., decouple
      the effects of trunk flexion posture from trunk moment. Systems identification
      analyses identified reflex gain by quantifying the relation between applied force
      disturbances and time-dependent EMG response in the lumbar paraspinal muscles.
      Trunk stiffness was characterized from a second order model describing the
      dynamic relation between the force disturbances versus the kinematic response of
      the torso. Trunk stiffness increased significantly with flexion angle and
      exertion level. This was attributed to passive tissue contributions to stiffness.
      Reflex gain declined significantly with trunk flexion angle but increased with
      exertion level. These trends were attributed to correlated changes in baseline
      EMG recruitment in the lumbar paraspinal muscles. Female subjects demonstrated
      greater reflex gain than males and the decline in reflex gain with flexion angle
      was greater in females than in males. Results reveal that torso flexion
      influences neuromuscular factors that control spinal stability and suggest that
      posture may contribute to the risk of instability injury.

PMID- 17196828
TI  - Voluntary activation of the triceps surae in prepubertal children.
AB  - The activation capacities and neuromuscular efficiency (NME) of the triceps surae
      (TS) of prepubescent children (7-11 years) and adults were evaluated during
      submaximal and maximal (MVC) isometric plantarflexion to determine whether they
      varied with age. TS-EMG were obtained by summing-up the rectified electromyograms
      of the soleus and gastrocnemii muscles; these data were quantified using a
      sliding average method and normalized with reference to the TS maximal compound
      action potential (TS-M-wave). The maximal EMG increased significantly with age in
      the children, but less than MVC, what led to a significant increase in NME(Max)
      (MVC/TS-EMG(max) ratio). The EMG-torque relationship indicated an age-related
      overactivation of TS at low torque, what led to a lower NME(Sub-max) (inverse of
      the slope of the EMG-torque relationship) for the youngest children. The
      overactivation of TS was accompanied by contraction of the TA, which decreased
      with age. The youngest children were also less able to maintain a target torque
      and muscle activation. Finally, the twitch interpolated method revealed an age
      dependant activation deficit. We conclude that central mechanisms are the main
      cause of the lower torques developed by children and they appear to vary with age
      in prepubertal children.

PMID- 17196829
TI  - The effect of increasing resistance on trunk muscle activity during extension and
      flexion exercises on training devices.
AB  - Although progressive resistance training of trunk muscles on devices is very
      common, today, the effects of increasing resistance on trunk muscle activity
      during dynamic extension and flexion movements on training devices have not been
      reported yet. Thirty healthy subjects participated in maximal isometric and
      submaximal dynamic (at 30%, 50% and 70% of maximum mean torque (MMT)) extension
      and flexion exercises on Tergumed lumbar training devices. The normalized (as a
      percentage of maximal voluntary isometric contractions (MVIC)) electromyographic
      activity of 16 abdominal and back muscles was investigated. The results of the
      present study indicated that in general, with increasing resistance from 30% MMT
      to 50% MMT and 70% MMT, the activity of all back muscles during the extension
      exercises and the activity of all abdominal muscles during the flexion exercises
      increased significantly. To train strength (>60% of MVIC), low intensities (30%
      and 50% MMT) appeared sufficient to affect the back muscles, but for the
      abdominals higher resistance (70% MMT) was required. In contrast to the other
      back muscles, the lumbar multifidus demonstrated high activity levels during both
      the extension and the flexion exercises. As the lumbar multifidus is demonstrated
      to be an important muscle in segmental stabilization of the lumbar spine, this
      finding may help in understanding the efficacy of rehabilitation programs using
      specific training devices.

PMID- 17196830
TI  - Adolescent development of motor imagery in a visually guided pointing task.
AB  - The development of action representation during adolescence was investigated
      using a visually guided pointing motor task (VGPT) to test motor imagery. Forty
      adolescents (24 males; mean age 13.1 years) and 33 adults (15 males; mean age
      27.5 years) were instructed to both execute and imagine hand movements from a
      starting point to a target of varying size. Reaction time (RT) was measured for
      both Execution (E) and Imagery (I) conditions. There is typically a close
      association between time taken to execute and image actions in adults because
      action execution and action simulation rely on overlapping neural circuitry.
      Further, representations of actions are governed by the same speed-accuracy trade
      off as real actions, as expressed by Fitts' Law. In the current study,
      performance on the VGPT in both adolescents and adults conformed to Fitts' Law in
      E and I conditions. However, the strength of association between E and I
      significantly increased with age, reflecting a refinement in action
      representation between adolescence and adulthood.

PMID- 17196831
TI  - Validation and optimization of statistical approaches for modeling odorant
      induced fMRI signal changes in olfactory-related brain areas.
AB  - Recent neuroimaging studies have converged to show that odorant-induced responses
      to prolonged stimulation in primary olfactory cortex (POC) are characterized by a
      rapidly habituating time course. Different statistical approaches have
      effectively modeled this time course. One approach explicitly modeled rapid
      habituation using an exponentially decaying reference waveform that decreased to
      baseline levels within 30 to 40 s. A second approach modeled an early transient
      response by simply shortening the odorant 'ON' period to be less than the actual
      stimulation period (i.e., 9 of 40 s). The goal of the current study was to
      validate, compare, and optimize these methodological approaches by applying them
      to an olfactory fMRI block-design dataset from 10 healthy young subjects
      presented with odorants for 12 s (ON), alternating with 30 s of clear air (OFF).
      Both approaches significantly improved sensitivity to odorant-induced signal
      changes in POC relative to a square-wave model based on the actual stimulation
      period. Our findings further demonstrate that the 'optimal' model fit to the data
      was achieved by shortening the odorant 'ON' period to approximately 6 s. These
      results suggest that sensitivity to odorant-induced POC activity in block-design
      experiments can be optimized by modeling an early phasic response followed by a
      precipitous rather than specific exponential decrease to baseline levels.
      Notably, whole brain voxel-wise analyses further established that modeling rapid
      habituation in this way is not only sensitive, but also highly specific to
      odorant-induced activation in a well-established network of olfactory-related
      brain areas.

PMID- 17196832
TI  - Temporal classification of multichannel near-infrared spectroscopy signals of
      motor imagery for developing a brain-computer interface.
AB  - There has been an increase in research interest for brain-computer interface
      (BCI) technology as an alternate mode of communication and environmental control
      for the disabled, such as patients suffering from amyotrophic lateral sclerosis
      (ALS), brainstem stroke and spinal cord injury. Disabled patients with
      appropriate physical care and cognitive ability to communicate with their social
      environment continue to live with a reasonable quality of life over extended
      periods of time. Near-infrared spectroscopy is a non-invasive technique which
      utilizes light in the near-infrared range (700 to 1000 nm) to determine cerebral
      oxygenation, blood flow and metabolic status of localized regions of the brain.
      In this paper, we describe a study conducted to test the feasibility of using
      multichannel NIRS in the development of a BCI. We used a continuous wave 20
      channel NIRS system over the motor cortex of 5 healthy volunteers to measure
      oxygenated and deoxygenated hemoglobin changes during left-hand and right-hand
      motor imagery. We present results of signal analysis indicating that there exist
      distinct patterns of hemodynamic responses which could be utilized in a pattern
      classifier towards developing a BCI. We applied two different pattern recognition
      algorithms separately, Support Vector Machines (SVM) and Hidden Markov Model
      (HMM), to classify the data offline. SVM classified left-hand imagery from right
      hand imagery with an average accuracy of 73% for all volunteers, while HMM
      performed better with an average accuracy of 89%. Our results indicate potential
      application of NIRS in the development of BCIs. We also discuss here future
      extension of our system to develop a word speller application based on a cursor
      control paradigm incorporating online pattern classification of single-trial NIRS
      data.

PMID- 17196835
TI  - Beamformer reconstruction of correlated sources using a modified source model.
AB  - This paper introduces a lead field formulation for use in beamformer analysis of
      MEG data. This 'dual source beamformer' is a technique to image two temporally
      correlated sources using beamformer methodology. We show that while the standard,
      single source beamformer suppresses the reconstructed power of two spatially
      separate but temporally correlated sources, the dual source beamformer allows for
      their accurate reconstruction. The technique is proven to be accurate using
      simulations. We also show that it can be used to image accurately the auditory
      steady state response, which is correlated between the left and right auditory
      cortices. We suggest that this technique represents a useful way of locating
      correlated sources, particularly if a seed location can be defined a priori for
      one of the two sources. Such a priori information could be based on previous
      studies using similar paradigms, or from other functional neuroimaging
      techniques.

PMID- 17196834
TI  - Top-down processes during auditory phoneme categorization in dyslexia: a PET
      study.
AB  - While persistence of subtle phonological deficits in dyslexic adults is well
      documented, deficit of categorical perception of phonemes has received little
      attention so far. We studied learning of phoneme categorization during an
      activation H(2)O(15) PET experiment in 14 dyslexic adults and 16 normal readers
      with similar age, handedness and performance IQ. Dyslexic subjects exhibited
      typical, marked impairments in reading and phoneme awareness tasks. During the
      PET experiment, subjects performed a discrimination task involving sine wave
      analogues of speech first presented as pairs of electronic sounds and, after
      debriefing, as syllables /ba/ and /da/. Discrimination performance and brain
      activation were compared between the acoustic mode and the speech mode of the
      task which involved physically identical stimuli; signal changes in the speech
      mode relative to the acoustic mode revealed the neural counterparts of
      phonological top-down processes that are engaged after debriefing. Although
      dyslexic subjects showed good abilities to learn discriminating speech sounds,
      their performance remained lower than those of normal readers on the
      discrimination task over the whole experiment. Activation observed in the speech
      mode in normal readers showed a strongly left-lateralized pattern involving the
      superior temporal, inferior parietal and inferior lateral frontal cortex. Frontal
      and parietal subparts of these left-sided regions were significantly more
      activated in the control group than in the dyslexic group. Activations in the
      right frontal cortex were larger in the dyslexic group than in the control group
      for both speech and acoustic modes relative to rest. Dyslexic subjects showed an
      unexpected large deactivation in the medial occipital cortex for the acoustic
      mode that may reflect increased effortful attention to auditory stimuli.

PMID- 17196833
TI  - Imaging signal transduction via arachidonic acid in the human brain during visual
      stimulation, by means of positron emission tomography.
AB  - BACKGROUND: Arachidonic acid (AA, 20:4n-6), an important second messenger, is
      released from membrane phospholipid following receptor mediated activation of
      phospholipase A(2) (PLA(2)). This signaling process can be imaged in brain as a
      regional brain AA incorporation coefficient K*. HYPOTHESIS: K* will be increased
      in brain visual areas of subjects submitted to visual stimulation. SUBJECTS AND
      METHODS: Regional values of K* were measured with positron emission tomography
      (PET), following the intravenous injection of [1-(11)C]AA, in 16 healthy
      volunteers subjected to visual stimulation at flash frequencies 2.9 Hz (8
      subjects) or 7.8 Hz (8 subjects), compared with the dark (0 Hz) condition.
      Regional cerebral blood flow (rCBF) was measured with intravenous [(15)O]water
      under comparable conditions. RESULTS: During flash stimulation at 2.9 Hz or 7.8
      Hz vs. 0 Hz, K* was increased significantly by 2.3-8.9% in Brodmann areas 17, 18
      and 19, and in additional frontal, parietal and temporal cortical regions. rCBF
      was increased significantly by 3.1-22%, often in comparable regions. Increments
      at 7.8 Hz often exceeded those at 2.9 Hz for both K* and rCBF. Decrements in both
      parameters also were produced, particularly in frontal brain regions.
      CONCLUSIONS: AA plays a role in signaling processes provoked by visual
      stimulation, since visual stimulation at flash frequencies of 2.9 and 7.8 Hz
      compared to 0 Hz modifies both K* for AA and rCBF in visual and related areas of
      the human brain. The two-stimulus condition paradigm of this study might be used
      with PET to image effects of other functional activations and of drugs on brain
      signaling via AA.

PMID- 17196836
TI  - Molecular phylogeny and biogeography of West Indian frogs of the genus
      Leptodactylus (Anura, Leptodactylidae).
AB  - Three endemic species of the aquatic-breeding frog genus Leptodactylus are
      recognized from the West Indies: Leptodactylus albilabris (Puerto Rico and the
      Virgin Islands), Leptodactylus dominicensis (Hispaniola), and Leptodactylus
      fallax (Lesser Antilles). DNA sequences were obtained from several mitochondrial
      genes to resolve taxonomic questions involving these species and to provide
      insights into their origin and distribution in the islands. We found low levels
      of sequence divergence between L. dominicensis and L. albilabris, supporting
      morphological evidence that the former species is a junior synonym of the latter
      species. Phylogenetic analysis supported previous species-group allocations,
      finding that L. albilabris is a member of the fuscus group and L. fallax is a
      member of the pentadactylus group. Molecular time estimates for the divergence of
      L. albilabris from its closest relative in South America (24-58 million years
      ago, Ma) and for L. fallax from its closest relative in South America (23-34Ma)
      indicate that they colonized the West Indies independently by over-water
      dispersal in the mid-Cenozoic. The absence of detectable sequence divergence
      between the two extant populations of L. fallax (Dominica and Montserrat), a
      species used for human food and now critically endangered, suggests that one or
      both arose by human introduction from an island or islands where that species
      originated. The relatively minor genetic differentiation of populations of L.
      albilabris can be explained by vicariance and dispersal in the Pleistocene and
      Holocene, although human introduction of some populations cannot be ruled out.

PMID- 17196837
TI  - Phylogeny and Bayesian divergence time estimations of small-headed flies
      (Diptera: Acroceridae) using multiple molecular markers.
AB  - The first formal analysis of phylogenetic relationships among small-headed flies
      (Acroceridae) is presented based on DNA sequence data from two ribosomal (16S and
      28S) and two protein-encoding genes: carbomoylphosphate synthase (CPS) domain of
      CAD (i.e., rudimentary locus) and cytochrome oxidase I (COI). DNA sequences from
      40 species in 22 genera of Acroceridae (representing all three subfamilies) were
      compared with outgroup exemplars from Nemestrinidae, Stratiomyidae, Tabanidae,
      and Xylophagidae. Parsimony and Bayesian simultaneous analyses of the full data
      set recover a well-resolved and strongly supported hypothesis of phylogenetic
      relationships for major lineages within the family. Molecular evidence supports
      the monophyly of traditionally recognised subfamilies Philopotinae and Panopinae,
      but Acrocerinae are polyphyletic. Panopinae, sometimes considered "primitive"
      based on morphology and host-use, are always placed in a more derived position in
      the current study. Furthermore, these data support emerging morphological
      evidence that the type genus Acrocera Meigen, and its sister genus Sphaerops, are
      atypical acrocerids, comprising a sister lineage to all other Acroceridae. Based
      on the phylogeny generated in the simultaneous analysis, historical divergence
      times were estimated using Bayesian methodology constrained with fossil data.
      These estimates indicate Acroceridae likely evolved during the late Triassic but
      did not diversify greatly until the Cretaceous.

PMID- 17196839
TI  - Phylogenetic analysis, genome evolution and the rate of gene gain in the
      Herpesviridae.
AB  - We used complete sequence data from 30 complete Herpesviridae genomes to
      investigate phylogenetic relationships and patterns of genome evolution. The
      approach was to identify orthologous gene clusters among taxa and to generate a
      genomic matrix of gene content. We identified 17 genes with homologs in all 30
      taxa and concatenated a subset of 10 of these genes for phylogenetic inference.
      We also constructed phylogenetic trees on the basis of gene content data. The
      amino acid and gene content phylogenies were largely concordant, but the amino
      acid data had much higher internal support. We mapped gene gain events onto the
      phylogenetic tree by assuming that genes were gained only once during the
      evolution of herpesviruses. Thirty genes were inferred to be present in the
      ancestor of all herpesvirus, a number smaller than previously hypothesized. Few
      genes of recent origin within herpesviruses could be identified as originating
      from transfer between virus and vertebrate hosts. Inferred rates of gene gain
      were heterogeneous, with both taxonomic and temporal biases. Nonetheless, the
      average rate of gene gain was approximately 3.5 x 10(-7) genes gained per year,
      which is an order of magnitude higher than the nucleotide mutation rate for these
      large DNA viruses.

PMID- 17196838
TI  - Evolution of host specialization in the Adelgidae (Insecta: Hemiptera) inferred
      from molecular phylogenetics.
AB  - The Adelgidae form a small group of insects in the Aphidoidea. They are
      cyclically parthenogenetic with host alternating, multiple-generation complex
      life cycles and are restricted to certain host genera in the Pinaceae. Species
      that host alternate always have Picea as the primary host where sexual
      reproduction and gall formation occur, and another genus in the Pinaceae as the
      secondary host where a series of parthenogenetic generations are produced. Other
      species that do not host alternate complete their entire life cycle on one host
      and only reproduce parthenogenetically. We studied relationships within Adelgidae
      using DNA sequences from the mitochondrial COI, COII, and cytb genes, and the
      nuclear EF1alpha gene. Analysis of the combined data resulted in a well-resolved
      phylogeny in which the major adelgid clades correspond neatly to their
      association with secondary host genera. Specialization on each secondary host
      genus occurred only once and was followed by diversification on the host genus.
      Molecular dating of divergence times in the Adelgidae suggest that
      diversification among host genera occurred in the Late Cretaceous and Early
      Tertiary when the Pinaceae genera were diverging. It is not clear, however,
      whether the Adelgidae and Pinaceae co-diversified because the relationships among
      the Pinaceae genera are not fully resolved. We discuss implications for adelgid
      taxonomy, life cycle evolution, and evolution of the interaction between adelgids
      and their host plants.

PMID- 17196840
TI  - Systematic, taxonomic and biogeographic relationships of Argentine flat oysters.

PMID- 17196842
TI  - In situ trapping of initiator caspases reveals intermediate surprises.
AB  - A novel method to identify initiator caspases is an in situ trapping approach
      using a cell-permeable biotinylated caspase inhibitor valine-alanine-aspartate
      fluoromethyl ketone (bVAD) that binds covalently and irreversibly to the active
      cysteine site of caspases. This inhibits apoptosis and should allow precipitation
      of initiator caspases in their uncleaved forms. However, in our experiments TRAIL
      and FasL-induced apoptosis and bVAD labelling did not result in streptavidin
      precipitation of the procaspase-8 forms, but led to the pull-down of the
      intermediate and to a lesser extent fully cleaved forms (p41/43 and p18). These
      findings are contrary to other reports and are of relevance to apoptosis research
      as they challenge the general concept of the bVAD approach that procaspases are
      being trapped. We show that (partially) processed forms of initiator caspases
      rather than procaspases might be precipitated with this method.

PMID- 17196841
TI  - Down-regulation of IGF-IR using small, interfering, hairpin RNA (siRNA) inhibits
      growth of human lung cancer cell line A549 in vitro and in nude mice.
AB  - Type I insulin-like growth factor receptor (IGF-IR), which is frequently
      overexpressed in a variety of human cancers including lung cancer, mediates
      cancer cell proliferation and tumor growth. In this study, we used a human U6
      promoter-driven DNA-template approach to induce hairpin RNA (hpRNA)-triggered
      RNAi to silence IGF-IR gene expression in the human lung cancer cell line A549,
      and then evaluate its effects on apoptosis, apoptosis-related gene expression,
      and the growth of tumor cells in vitro and in nude mice. IGF-IR expression levels
      were found to markedly decrease in cells transfected with a plasmid expressing
      hairpin siRNA for IGF-IR (by more than 78.9%). Down-regulation of IGR-IR
      concomitantly accompanied reduction of bcl-2 as well as pERK and pAkt levels,
      activation of caspase-3, apoptosis and growth inhibition of A549 cells in vitro.
      Direct intratumoral injections of plasmid DNA expressing hpRNA for IGF-IR
      significantly regressed pre-established tumors in nude mice. Our results support
      the therapeutic potential of RNAi as a method for gene therapy in treating lung
      cancer.

PMID- 17196843
TI  - Effect of therapeutic pulsed ultrasound on parameters of oxidative stress in
      skeletal muscle after injury.
AB  - Contusion injuries are a very common form of both athletic and non-athletic
      injury, that effect muscle function. Treatments to augment the normal repair and
      regeneration processes are important for a wide variety of patients. Therapeutic
      ultrasound has been claimed to promote tissue repair, especially by enhancing
      cell proliferation and protein synthesis. The present study aimed to investigate
      the effect of therapeutic pulsed ultrasound (TPU) on parameters of oxidative
      stress, namely thiobarbituric acid-reactive substances (TBARS), protein carbonyl
      content and the activities of antioxidant enzymes, catalase and superoxide
      dismutase (SOD), in skeletal muscle after injury. Wistar rats were submitted to
      an animal model of muscle (gastrocnemius) laceration. TPU was used once a day.
      One, three or five days after muscle laceration, the animals were killed by
      decapitation and oxidative stress parameters were evaluated. Serum CK levels were
      increased in muscle-injured animals, indicating that the laceration animal model
      was successful. TBARS were not altered after muscle injury, when compared to the
      sham group. Protein carbonyl content was increased after muscle laceration.
      Catalase and SOD activities were increased 1 day after muscle injury and not
      altered at days 3 and 5. TPU decreased TBARS levels after muscle laceration when
      compared to injured muscle animals without treatment. Protein carbonyl content
      evaluation presented similar results. It is tempting to speculate that TPU seems
      to protect the tissue from oxidative injury. TPU diminished catalase and SOD
      activities, especially on the first day following muscle laceration.

PMID- 17196844
TI  - Effect of NYD-SP27 down-regulation on ATP-induced Ca2+-dependent pancreatic duct
      anion secretion in cystic fibrosis cells.
AB  - Our previous study demonstrated that NYD-SP27 is a novel inhibitory PLC isoform
      expressed endogenously in human pancreas and upregulated in CFPAC-1 cells. The
      present study investigated the effect of NYD-SP27 down-regulation on the ATP
      stimulated and Ca(2+)-dependent pancreatic anion secretion by CFPAC-1 cell line
      using short-circuit current (I(SC)) recording. NYD-SP27 antisense-transfected
      CFPAC-1 (AT-CF) cells exhibited a significantly higher basal transmembrane
      potential difference and current than those of empty vector-transfected CFPAC-1
      (VT-CF) cells. Cl(-) channel blocker, DPC or Glibenclamide (1mM), and inhibitor
      of Na(+)-K(+)-Cl(-) cotransporter, bumetanide (100 microM) significantly
      inhibited the basal current in AT-CF cells. The inhibitor of adenylate cyclase,
      MDL12330A (20 microM), and Ca(2+)-dependent Cl(-) channel (CaCC) blocker, DIDS
      (100 microM) also significantly reduced the basal current in AT-CF. Apical
      application of ATP (10 microM) stimulated a fast transient I(SC) increase in VT
      CF cells, but a more sustained rise with slower decline in AT-CF cells.
      Pretreatment with BAPTA-AM (50 microM) reduced the ATP-induced I(SC) response in
      AT-CF cells by 77.9%. PMA (1 microM), a PKC activator, inhibited the ATP
      stimulated current increase (the transient peak) in VT-CF cells, but had no
      effect on the AT-CF cells. However, PKC inhibitor, staurosporine (40 microM)
      could inhibit the ATP-induced I(SC) response in AT-CF cells. The present results
      confirm the previously proposed inhibitory role of NYD-SP27 in the PLC pathway
      and demonstrate that the suppression of its expression could result in an
      enhancement of ATP-stimulated Ca(2+) dependent pancreatic anion secretion.

PMID- 17196845
TI  - In vitro differentiation of cord blood unrestricted somatic stem cells expressing
      dopamine-associated genes into neuron-like cells.
AB  - An intensive study is underway to evaluate different potential candidates for
      cell therapy of neurodegenerative disorders such as Parkinson's disease (PD).
      Availability and lower immunogenicity compared to other sources for stem cell
      therapy such as bone marrow have made human umbilical cord blood stem cells a
      considerable source for cell therapy. The present study aimed to investigate
      differentiation of recently introduced pluripotent cord blood stem cells, known
      as unrestricted somatic stem cells (USSCs), into cells with neural features in
      serum-withdrawal medium. Using reverse transcription polymerase chain reaction
      and immunocytochemistry assays, we have shown the expression of neuron-specific
      genes following a 2week treatment of USSCs in serum-withdrawal induction medium.
      In addition, we have found that USSCs and USSC-derived neuron-like cells express
      transcripts of genes associated with development and/or survival of dopaminergic
      mesencephalic neurons including En1, En2, Nurr1, Ptx3, Pax2, Wnt1 and Wnt3a. The
      expression of dopamine-associated genes suggests that these cells may be
      potential candidates to be used for cell therapy of PD.

PMID- 17196846
TI  - Ischemic cerebral lesions after carotid surgery and carotid stenting.
AB  - OBJECTIVES: To evaluate the risk of new ischemic cerebral lesions after carotid
      endarterectomy and carotid stenting and their clinical significance. METHODS:
      Prospective and non-randomized single-center study including 121 patients with
      symptomatic and asymptomatic significant carotid stenosis. 60 patients were
      treated by surgery and 61 treated by carotid stenting. Stenting was restricted to
      patients at high risk for surgery. Neurological examination and Diffusion
      Weighted Cerebral Magnetic Resonance (DW-MRI) were performed before and after
      each procedure. The presence, location and volume of new cerebral lesions were
      determined. RESULTS: In the surgical group, 2 minor strokes were registered. DW
      MRI showed new lesions in 7 patients (11.6%). All except one were located in the
      ipsilateral anterior circulation. In the stenting group, 1 minor stroke and 1
      occurrence of quadranopsia were registered. DW-MRI showed new lesions in 26
      patients (42.6%). 10 of these patients (38.4%) had lesions in the contralateral
      hemisphere and 7 patients (26.9%) in the posterior circulation. Deficits are
      found in patients with higher lesion volumes. CONCLUSIONS: Cerebral ischemic
      lesions are significantly (p<0.0001) more frequent after carotid stenting than
      after endarterectomy. The majority of these lesions have no immediate clinical
      implication, but more specific tests are needed to evaluate their exact
      significance.

PMID- 17196847
TI  - Comparison of mortality prediction models after open abdominal aortic aneurysm
      repair.
AB  - OBJECTIVES: Comparison of the accuracy of prediction of contemporary mortality
      prediction models after open Abdominal Aortic Aneurysm (AAA) surgery. METHODS:
      Post-operative data were collected from AAA patients from 2 UK Intensive Care
      Units (ICU). POSSUM and VBHOM based models were compared to the APACHE-AAA model
      which was able to adjust for the hospital-related effect on outcome. Model
      performance was assessed using measures of calibration, discrimination and
      subgroup analysis. RESULTS: 541 patients were studied. The in-hospital mortality
      rate for elective AAA repair (325 patients) was: 6.2% (95% confidence interval
      (c.i.) 3.5 to 8.8) and for emergency repair (216 patients) was: 28.7% (95% c.i.
      22.5-34.9). The APACHE-based model had the best overall fit to the whole
      population of AAA patients, and also separately in elective and emergency
      patients. The V-POSSUM physiology-only (p<0.001) and VBHOM (p=0.011) models had a
      poor fit in elective patients. The RAAA-POSSUM physiology-only (p<0.001) and
      VBHOM models (p=0.010) had a poor fit in emergency patients. CONCLUSIONS: The
      APACHE-AAA model with its ability to adjust for both the hospital-related
      "effect" as well as the patient case-mix, was a more accurate risk stratification
      model than other contemporary models, in the post-operative AAA patient managed
      in ICU.

PMID- 17196848
TI  - Vascular involvement in diabetic subjects with ischemic foot ulcer: a new
      morphologic categorization of disease severity.
AB  - OBJECTIVES: Arteriographic lesions of diabetic subjects with critical limb
      ischemia (CLI) and ischemic foot ulcer were reviewed retrospectively, to provide
      new criteria for stratification of these patients on the basis of their vascular
      involvement. PATIENTS: In 417 consecutive CLI diabetic subjects with ischemic
      foot ulcer undergoing lower limb angiography, lesions were defined as stenosis or
      occlusion, localization, and length (<5 cm, 5-10 cm, >10 cm). In a subgroup of
      389 subjects, foot arteries also were evaluated. Patients then were categorized
      into 7 classes of progressive vascular involvement based on angiographic
      findings. RESULTS: Of the 2893 found lesions (55% occlusions) 1% were in the
      iliac arteries, whereas 74% were in below-the-knee (BTK) arteries. Sixty-six % of
      all BTK lesions were occlusions, and 50% were occlusions >10 cm (p<0.001 vs
      proximal segments). Occlusions of all BTK were present in 28% of patients,
      although there was patency of at least one foot artery in 55% of patients. The
      morphologic Class 4 (two arteries occluded and multiple stenoses of
      tibial/peroneal and/or femoral/popliteal vessels) was the most common (36%). An
      inverse correlation between morphologic class and TcPO2 was observed (r=-0.187,
      p=0.003). CONCLUSIONS: In CLI diabetic subjects with ischemic foot ulcer, the
      vascular involvement is extremely diffuse and particularly severe in tibial
      arteries, with high prevalence of long occlusions. A new morphologic
      categorization of these patients is proposed.

PMID- 17196849
TI  - Myocardial damage in high-risk patients undergoing elective endovascular or open
      infrarenal abdominal aortic aneurysm repair.
AB  - OBJECTIVE: Dobutamine stress echocardiography (DSE) provides an objective
      assessment of the presence and extent of coronary artery disease. Therefore we
      compared cardiac outcome in patients at high-cardiac risk undergoing open or
      endovascular repair of infrarenal AAA using preoperative DSE results. METHODS:
      Consecutive patients with >or=3 cardiac risk factors (age >70 years, angina
      pectoris, myocardial infarction, heart failure, stroke, renal failure, and
      diabetes mellitus) undergoing infrarenal AAA repair were reviewed
      retrospectively. All underwent cardiac stress testing using DSE. Postoperatively
      data on troponin release and ECG were collected on day 1, 3, 7, before discharge,
      and on day 30. The main outcome measures were perioperative myocardial damage and
      myocardial infarction or cardiovascular death. RESULTS: All 77 patients (39
      endovascular, 38 open) had a history of cardiac disease. The number and type of
      cardiac risk factors were similar in both groups. Also DSE results were similar:
      55 vs 56%, 24 vs 28%, and 21 vs 18% had no, limited, or extensive stress induced
      myocardial ischemia respectively. The incidence of perioperative myocardial
      damage (47% vs 13%, p=0.001) and the combination of myocardial infarction or
      cardiovascular death (13% vs 0%, p=0.02) was significantly lower in patients
      receiving endovascular repair. CONCLUSION: In patients with similar high cardiac
      risk, endovascular repair of infrarenal aortic aneurysms is associated with a
      reduced incidence of perioperative myocardial damage.

PMID- 17196850
TI  - Intermittent claudication: a plea for guidelines for medical management.

PMID- 17196851
TI  - Characteristics and treatments of patients with peripheral arterial disease
      referred to UK vascular clinics: results of a prospective registry.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is often associated with risk
      factors including cigarette smoking, hypertension and hypercholesterolaemia, and
      patients have a high risk of future vascular events. Good medical management
      results in improved outcomes and quality of life, but previous studies have
      documented sub-optimal treatment of risk factors. We assessed the management of
      cardiovascular risk factors in patients with PAD referred to specialist vascular
      clinics. METHODS: This was a prospective, protocol driven registry carried out in
      UK vascular clinics. Patients who were first-time referrals for evaluation of PAD
      were eligible if they had claudication plus ankle-brachial pressure index (ABPI)
      < or = 0.9. Statistical associations between key demographic and treatment
      variables were explored using a chi-squared test. RESULTS: We enrolled 473
      patients from 23 sites. Mean age was 68 years (SD 10) and 66% were male. Mean
      estimated claudication distance was 100 m, and ABPI was 0.74. Mean systolic blood
      pressure (SBP) was 155 mmHg, and 42% had a SBP >160 mmHg. Forty percent were
      current smokers and half had tried to give up in the prior 6 months, but there
      was no evidence of a systematic method of smoking cessation. Mean total
      cholesterol was 5.4 (SD1.2) mmol/l and 30% had levels >6 mmol/l. Antiplatelet
      therapy had been given to 70% and statins to 44%. Prior CHD was present in 29%
      and these patients had significantly higher use of antiplatelet therapy, statins
      and ACE-inhibitors. CONCLUSIONS: In spite of attempts to raise awareness about
      PAD as an important marker of cardiovascular risk, patients are still poorly
      treated prior to referral to a vascular clinic. In particular, the use of
      evidence-based treatments is sub-optimal, while hypertension and cigarette
      smoking are poorly managed. More work needs to be done to educate health
      professionals about the detection and optimal medical management of PAD.

PMID- 17196852
TI  - Dialysis fistulae patency and preoperative diameter ultrasound measurements.
AB  - BACKGROUND: This study was designed to investigate the possibility of defining a
      vascular diameter with a practical cut-off point, which predicts a successful
      patency for radiocephalic arteriovenous fistulae in dialysis patients. METHODS:
      This is a retrospective analysis of prospectively gathered data. Consecutive
      patients (n=148) with chronic renal failure, needing vascular access for
      haemodialysis, were included if they underwent duplex ultrasound examination to
      evaluate preoperatively the vascular status and diameters for radiocephalic
      arteriovenous fistulae (RCAVF) construction. The associations between the
      diameter of the radial artery and cephalic vein and primary failure at six weeks,
      primary and secondary patency at one year were investigated. RESULTS: There was
      no significant association between either radial artery diameter or dilated
      cephalic vein diameter and primary failure. There was an association between
      radial artery diameter and primary patency (Overall P=0.042). Males had a
      significantly larger mean radial artery diameter than females (P=0.005). Gender
      did not influence primary patency. CONCLUSION: We recommend using radial artery
      diameters of > or = 2.1 mm and < or = 2.5 mm for RCAVF construction, this
      diameter category having the highest patency at 1 year. A single cut-off
      guideline cannot be recommended.

PMID- 17196853
TI  - Gaucher disease among Chinese patients: review on genotype/phenotype correlation
      from 29 patients and identification of novel and rare alleles.
AB  - Gaucher disease, the most prevalent lysosomal storage disease, results from an
      inherited deficiency in the enzyme glucocerebrosidase. Three clinical forms of
      Gaucher disease have been described: Type 1 non-neuronopathic, Type 2 acute
      neuronopathic, and Type 3 subacute neuronopathic. Although Gaucher disease is
      panethnic, its presentation reveals some ethnic-specific characteristics. The
      Type 1 form is most common among Caucasian patients. In contrast, the majority of
      Chinese Gaucher disease patients have early age of onset, severe hematological
      and skeletal complications, and often neurological involvement, resulting in
      early childhood death. In this report, we review 29 cases of Gaucher disease from
      23 unrelated patients and 6 patients from 3 non-consanguineous families. Among
      these patients, 13 were diagnosed as Type 1, 10 as Type 2, and 6 as Type 3. A
      novel mutation, del 205-209ACCTT, was identified in the heterozygous form with
      mutation R353W (c.1174C>T) by DNA sequence analysis in 2 Type 1 patients who are
      sibs. Mutation R353W was also found in the heterozygous form in 3 other Type 1
      patients, with mutation L444P in 2 sibs and a second unknown Gaucher allele in
      the third patient. The Gaucher genotypes of the remaining Type 1 patients were
      F37V/L444P, G46E/L444P, R48W/R120W, N188S/L444P, Y205C/L444P, N370S/L444P, and
      L444P/unknown. It was noted that mutation N370S in the patient was linked to the
      pv1.1(-)(1) haplotype present in Jewish patients. Among the Type 2 patients,
      L444P was present in the heterozygous form with mutation F213I, L385P, or the
      complex allele (RecNci) in 5 patients. The second most common mutation, F213I,
      was found in the heterozygous form in 6 patients with mutations N382K, L383R, or
      L444P. The other mutations found in the Type 2 patients were P122L, V375L, Y363C,
      M416V, and 383-400del. The genotypes of the 6 Type 3 patients identified were
      D409H/D409H, D409H/G202R, G46E/N188S, N188S/unknown, and L444P/L444P. While D409H
      has been reported as being associated with cardiovascular/ocular involvements in
      Gaucher disease, there have been no such complications in these patients. As
      noted, the majority of the Gaucher mutations we identified in the Chinese
      patients were either rare or absent in other populations. With the exception of
      N370S and R353W found only in the Type 1 form, the majority of these mutations
      are severe ones that result in poor prognosis and often Types 2 and 3 Gaucher
      disease.

PMID- 17196854
TI  - The TRPV1 receptor and nociception.
AB  - The capsaicin receptor TRPV1 is an emerging target for the treatment of pain with
      a unique expression profile in peripheral nociceptors and the ability to show
      polymodal activation, TRPV1 is an important integrator of responses to
      inflammatory mediators. Sensitization of TRPV1 during chronic pain is believed to
      contribute to the transduction of noxious signaling for normally innocuous
      stimuli and consequently the search for novel TRPV1 therapeutics is intense. The
      current understanding of the physiological role the receptor, as well as the
      potential therapeutic utility and emerging liabilities of TRPV1 modulators are
      discussed.

PMID- 17196855
TI  - Circadian rhythmicity during prolonged chemostat cultivation of Neurospora
      crassa.
AB  - Following exposure to light and attainment of steady-state in the chemostat,
      Neurospora was grown in constant conditions of darkness at 25 degrees C for 6
      days. Biomass samples were taken every 4h for the extraction of RNA and protein,
      and the state of the circadian clock was assessed by assaying the levels of three
      rhythmically expressed mRNAs; frequency (frq), antisense frq (qrf) and clock
      controlled gene-14 (ccg-14), and by monitoring the clock-controlled rhythm of
      sporulation. Our results indicate that the Neurospora clock continued to run in
      the chemostat. This is the longest reported time that Neurospora has been grown
      in a chemostat in filamentous form and opens up the possibility of studying the
      response of Neurospora to a range of stimuli in the absence of confounding
      effects due to; alterations in growth rate, aging, and changing conditions of the
      growth medium.

PMID- 17196856
TI  - Long-term stability of rotor-controlled MAS frequencies to 0.1 Hz proved by 14N
      MAS NMR experiments and simulations.
AB  - Experimental and simulated 14N MAS NMR spectra of the NH4+ ions in the two
      polymorphs, mS60 and mP60, of (NH4)2MoO4 are used to illustrate that a long-term
      stability of rotor-controlled MAS frequencies to 0.1 Hz can be achieved using
      commercial instrumentation (MAS speed controller and 7.5 mm MAS probe with a
      single marked rotor) attached to a highly pressure-stabilized air supply. A new
      modification of the STARS simulation software employs a Gaussian distribution for
      the experimental spinning frequency around the frequency set for the MAS speed
      controller. A simulated spectrum is then obtained by summation of several
      calculated spectra for evenly spaced spinning frequencies around the set
      frequency with relative weight factors corresponding to the Gaussian
      distribution.

PMID- 17196857
TI  - How does blood cell concentration modulate cardiovascular parameters in
      developing zebrafish (Danio rerio)?
AB  - Blood flow and shear forces are considered to be important parameters possibly
      stimulating angiogenesis or cardiovascular remodeling. The main objective of this
      study was to test the hypothesis that a significant reduction in shear forces as
      a consequence of a significant isovolemic anemia induced by microsurgical
      techniques during early larval development of the zebrafish might induce a
      compensatory stimulation of erythropoiesis and/or induce a modification of
      cardiac activity or even the formation of the heart and may influence the shaping
      of the vascular bed. Blood from 2 day old zebrafish larvae was withdrawn and
      replaced by zebrafish Ringer's solution, so that the blood cell concentration was
      reduced by at least 75%. At 5 days post fertilization (dpf) a partial recovery in
      blood cell concentration was observed and reached a value of 814.55+/-85.42
      cells/nL, while in control animals blood cell concentration amounted to 1856.00+/
      131.59 cells/nL. At 7 dpf the value of blood cell concentration was 1023.89+/
      95.75 cells/nL versus 1701.54+/-146.03 cells/nL in control animals. Compared to
      control animals, heart rate and cardiac output were significantly reduced in
      anemic animals and alterations in the formation of the vascular bed were also
      observed. A significant decrease in the end-diastolic volume suggested that
      ventricular volume was reduced. Thus, within a few days zebrafish larvae were
      nearly able to compensate for an isovolemic anemia by an enhanced erythropoiesis.
      However, several changes in cardiovascular system indicated that phenotypic
      plasticity is established even at an early developmental stage.

PMID- 17196858
TI  - Is urea pulsing in toadfish related to environmental O2 or CO2 levels?
AB  - The neurochemical, serotonin (5-hydroxytryptamine; 5-HT) is involved in the
      regulation of toadfish pulsatile urea excretion as well as the teleost hypoxia
      response. Thus, the goal of this study was to determine whether environmental
      conditions that activate branchial chemoreceptors also trigger pulsatile urea
      excretion in toadfish, since environmental dissolved oxygen levels in a typical
      toadfish habitat show significant diel fluctuations, often reaching hypoxic
      conditions at dawn. Toadfish were fitted with arterial, venous and/or buccal
      catheters and were exposed to various environmental conditions, and/or injected
      with the O(2) chemoreceptor agonist NaCN or the 5-HT(2) receptor agonist alpha
      methyl-5HT. Arterial PO(2), as well as ammonia and urea excretion were monitored.
      Natural fluctuations in arterial PO(2) levels in toadfish did not correlate with
      the occurrence of a urea pulse. Chronic exposure (24 h) of toadfish to hyperoxia
      was without effect on nitrogen excretion, however, exposure to hypoxia caused a
      significant reduction in the frequency of urea pulses, and exposure to
      hypercapnia resulted in a reduction in the percentage of nitrogen waste excreted
      as urea. Of toadfish exposed acutely to hypoxia, 20% pulsed within 1 h, whereas
      none pulsed after normoxic or hypercapnic treatments. Furthermore, 20% of fish
      injected intravenously with NaCN pulsed within 1 h of injection, but no fish
      pulsed after injection of NaCN into the buccal cavity. To test whether
      environmental conditions affected 5-HT(2) receptors, toadfish were injected with
      alpha-methyl-5HT, which elicits urea pulses in toadfish. No significant
      differences in pulse size occurred among the various environmental treatments.
      Our findings suggest that neither the environmental conditions of hypoxia,
      hyperoxia or hypercapnia, nor direct branchial chemoreceptor activation by NaCN
      play a major role in the regulation of pulsatile urea excretion in toadfish.

PMID- 17196859
TI  - Cloning and characterization of 40S ribosomal protein S4 gene from Culex pipiens
      pallens.
AB  - The 40S ribosomal protein S4 gene (RPS4) has been cloned from Culex pipiens
      pallens. An open reading frame (ORF) of 789 bp was found to encode a putative 262
      amino acid protein. The deduced amino acid sequence shares 96% and 91% identity
      with RPS4 genes from Aedes and Anopheles respectively. Transcript expression of
      RPS4 was determined by real-time PCR in all life stages of deltamethrin
      susceptible and -resistant strains. The results demonstrated that this gene is
      expressed at all developmental stages. Meanwhile, in pupae and adults, RPS4 is
      overexpressed in deltamethrin-resistant strain than in -susceptible strain. Our
      data for the first time suggests that increased expression of the RPS4 gene may
      play some role in the development of deltamethrin resistance in C. pipiens
      pallens.

PMID- 17196860
TI  - Characterization of RR-1 and RR-2 cuticular proteins from Myzus persicae.
AB  - A cDNA library for Myzus persicae has served to identify sequences coding for
      cuticular proteins (CPs) with RR-1 and RR-2 consensus. Two putative CPs showed a
      common RR-2 chitin binding domain (CBD) but differed in their C and N terminals.
      Two other predicted CPs showed a typical RR-1 CBD but differed in size and
      sequence of the C and N terminals. An additional sequence encoding for a protein
      that showed terminal amino acid repeats similar to those of putative CPs from M.
      persicae, but lacked the R & R consensus, was also described. A comparison of the
      sequences obtained from the cDNA library with those attained from the genomic
      DNA, confirmed their identity as cuticular proteins genes. Presence of introns
      was revealed in the Mpcp4 and Mpcp5 genes coding for CPs with an RR-1 consensus.
      The Mpcp4 has a single large intron, while the Mpcp5 has two shorter ones.
      Introns were not found in the Mpcp2 and Mpcp3 genes encoding for CPs with RR-2
      consensus. Differences were also noticed for 3' UTR and 5' UTR of both the RR-1
      and RR-2 CPs. CPs genes were expressed in bacteria, and the resulting protein was
      identified as a CP by amino acid sequencing.

PMID- 17196861
TI  - Response of two species of clams, Ruditapes decussatus and Venerupis pullastra,
      to starvation: physiological and biochemical parameters.
AB  - Adult specimens of two species of clams, Ruditapes decussatus and Venerupis
      pullastra, were starved for 84 days to determine the effect of starvation on
      their metabolism. The energy cost of metabolism in starvation was assessed using
      the oxygen consumption rates (respiration rates) of the clams and assessing the
      type of fuel used to provide this energy by analyzing their biochemical
      composition. Respiration rates decreased in both species after 15 days of
      starvation and remained at basal levels throughout the rest of the experimental
      period. Both during the first period and also after the metabolism had slowed
      down, the amount of energy consumed in respiration was higher in V. pullastra
      than in R. decussatus. The energy needed to maintain vital functions in both
      species is obtained from catabolism of body components, with a reduction in dry
      mass of the specimens, and consequently their energy content, in both species.
      This reduction was greater in V. pullastra given that energy demand is higher in
      this species. In both species carbohydrates made the largest contributions to
      energy output, followed by lipids in males and proteins in females. However, the
      energy contribution of each biochemical component differs according to species:
      R. decussatus obtains its energy from the catabolism of carbohydrates and
      proteins in equal proportion, while V. pullastra obtains it from proteins and
      lipids. In both species, albeit to a greater extent in R. decussatus, we observed
      that female specimens conserved their lipids until the later stages of the period
      of starvation (day 70), after which they started to metabolise their lipid
      components more intensely. The interspecific differences are interpreted in
      relation to the different habitat occupied by the two species.

PMID- 17196862
TI  - Heterogeneity of mutations in the ferrochelatase gene in Italian patients with
      erythropoietic protoporphyria.
AB  - Mutations and a low-expressed allele IVS3-48c (in trans to the mutation) of the
      ferrochelatase (FECH) gene are responsible for erythropoietic protoporphyria
      (EPP) which is characterized clinically by cutaneous photosensitivity. In this
      study of 15 Italian EPP families, we identified 10 different FECH gene mutations,
      six of them were novel mutations (Q32X; IVS2-2, a-->g; IVS3-67, g-->a; 488-501del
      14bp; IVS5-3, c-->t and 757-761delAGAAG). Four were known mutations (213insT;
      R115X; S264L and 899-900delTG). Real-time PCR quantification of FECH mRNA from a
      patient carrying mutation IVS-67, g-->a revealed a 51% reduction in the normal
      FECH transcript. This mutation generated an abnormal mRNA species with a 63-bp
      intron 3 retention--the same mRNA species which the low-expressed FECH allele
      IVS3-48c also produces. In addition, a double intronic deletion (IVS8-61 del ag
      /IVS9-58 del a) was found in some patients as well as their healthy relatives of
      this cohort. Sequencing of 50 Italian control subjects revealed an 11% prevalence
      of the double deletion. However, the double intronic deletion is not a disease
      causing mutation as evidenced by a normal amount of FECH mRNA measured from a non
      porphyric individual who carried the double deletion. Another interesting finding
      of this study was a 1% prevalence of IVS3-48c allele in the white Italian
      population, comparing to 11% in the French population. Further epidemiological
      studies are needed to test whether the 1% frequency of the low-expressed IVS3-48c
      allele is associated with a low prevalence of EPP in the white Italian
      population.

PMID- 17196863
TI  - Two alternative promoters regulate the expression of lysinuric protein
      intolerance gene SLC7A7.
AB  - The human SLC7A7 gene encodes y(+)L amino acid transporter-1 (y(+)LAT-1).
      Mutations in the SLC7A7 coding region cause a rare recessive disorder, lysinuric
      protein intolerance (LPI). LPI is enriched in the Finnish population, where all
      patients carry the same homozygous founder mutation. Although the same LPI
      genotype is present in all patients, clinical symptoms vary greatly and thus show
      no genotype-phenotype correlation. In LPI, the transport of cationic amino acids
      is functionally affected at least at the basolateral membrane of the polarised
      epithelial cells in the kidney tubules and small intestine, although SLC7A7 is
      expressed much more widely. Interestingly, some LPI patients' tissues exhibit
      normal cationic amino acid transport despite the mutations leading to clinical
      phenotype. When studying the various manifestations of this monogenic disorder
      and the tissue specificity of the transport defect, it is crucial to know the
      transcriptional regulatory mechanisms of SLC7A7 gene. In this study, we have
      identified a novel alternative, TATA-box-containing promoter that plays a role in
      the tissue-specific regulation of the SLC7A7 gene expression. This newly found
      downstream promoter in front of exon 2 seems to be active in tissues with strong
      defects in the function of the transporter in patients with LPI.

PMID- 17196864
TI  - Blood transfusion in Europe: basic principles for initial and continuous training
      in transfusion medicine: an approach to an European harmonisation.
AB  - Over the past few decades, transfusion medicine and haemotherapy have evolved
      into complex medical disciplines comprising a broad field of subspecialties such
      as immunohaematology, blood component production, haemapheresis and
      haemostaseology. Transfusion medicine is thus an important qualification at the
      interfaces of analytical laboratory medicine, pharmaceutical production and
      clinical disciplines such as internal medicine, anaesthesiology or surgery.
      Physicians specialising in transfusion medicine are valuable and competent
      partners for these related disciplines when it comes to safe, effective and
      tailored haemotherapy. Why has transfusion medicine become so complex? On the one
      hand, one can discern problems such as infectious diseases like the HIV disaster
      in the past century, resulting in guidelines, directives and laws such as the
      transfusion law in Germany. Thereby, we now enjoy the highest level of blood
      product safety ever regarding viral transmission thanks to the broad
      implementation of PCR testing. On the other hand, there are numerous positive
      reasons for the increasing complexity of transfusion medicine: Modern medical
      therapies like stem cell transplantation, cellular therapy, transplantation of
      solid organs, regenerative medicine and surgery cannot exist without a safe
      supply of blood products and high quality standard as well as special blood
      products and laboratory services provided by blood banks and transfusion medicine
      specialists. Good laboratory practice (GLP), good manufacturing practice (GMP),
      quality management systems and quality control on the pharmaceutical
      manufacturer's level are only few examples of the standards in today's blood
      banking. European directives in the field of blood products, stem cell
      preparations and tissue have led to higher uniform quality standards for
      biological preparations in a unified Europe, which is the desired outcome, but
      which also increases the complexity of this field. In contrast, directives
      93/16/EEC and 2001/19/EC, the directives of the European Parliament and of the
      Council on the mutual recognition of professional qualifications of European
      doctors currently in force, as well as the impending directive 2005/36/EC, which
      has to be translated into national law until October 2007, do not include
      transfusion medicine, blood transfusion or immunohaematology at all. Other
      medical specialities, which like our field, are not common to all member states
      of the European Union, are listed in the above mentioned directives with the
      minimum length of training and minimal requirements for the qualifications.
      Examples include clinical biology, biological haematology, microbiology
      bacteriology, biological chemistry, immunology, thoracic, paediatric or vascular
      surgery as well as physiotherapy, stomatology, neuro-psychiatry, dermato
      venerology, occupational medicine, allergology, geriatrics, gastro-enterological
      surgery, community medicine, nuclear medicine, pharmacology, accident and
      emergency medicine or tropical medicine. Most of the above are medical
      specialities in some member states, but not in all. A concerted initiative
      inaugurated by the European Network of Transfusion Medicine Societies (EuroNet
      TMS) and the European Blood Alliance (EBA) aims to compile the situation of the
      transfusion medicine speciality throughout Europe. A preliminary summary of the
      current situation in 15 European states was prepared in 2005 after a first set of
      questions, which was sent out by us via the EBA platform. The authors appreciate
      Clair Watts' compilation of the answers provided by the 15 European colleagues. A
      summary of these answers is depicted in Table 1. However, the initiative aims at
      a more complex analysis of the different requirements and constituent parts of
      the qualification in transfusion medicine in different countries. A long-term
      objective of this initiative might be to introduce the transfusion medicine
      specialisation into the above mentioned EC directives in order to facilitate
      mutual recognition of transfusion medicine qualifications throughout Europe.

PMID- 17196865
TI  - Toll-like receptor 4 (TLR4) is required for protective immunity to larval
      Strongyloides stercoralis in mice.
AB  - TLR4 is important for immunity to various unicellular organisms and has been
      implicated in the immune responses to helminth parasites. The immune response
      against helminths is generally Th2-mediated and studies have shown that TLR4 is
      required for the development of a Th2 response against allergens and helminth
      antigens in mice. C3H/HeJ mice, which have a point mutation in the Tlr4 gene,
      were used in this study to determine the role of TLR4 in protective immunity to
      the nematode Strongyloides stercoralis. It was demonstrated that TLR4 was not
      required for killing larval S. stercoralis during the innate immune response, but
      was required for killing the parasites during the adaptive immune response. No
      differences were seen in the IL-5 and IFN-gamma responses, antibody responses or
      cell recruitment between wild type and C3H/HeJ mice after immunization.
      Protective immunity was restored in immunized C3H/HeJ mice by the addition of
      wild type peritoneal exudate cells in the environment of the larvae. It was
      therefore concluded that the inability of TLR4-mutant mice to kill larval S.
      stercoralis during the adaptive immune response is due to a defect in the
      effector cells recruited to the microenvironment of the larvae.

PMID- 17196866
TI  - Brucella abortus bacA mutant induces greater pro-inflammatory cytokines than the
      wild-type parent strain.
AB  - The inner-membrane protein BacA affects Brucella LPS structure. A bacA deletion
      mutant of Brucella abortus, known as KL7 (bacA(mut)-KL7), is attenuated in BALB/c
      mice and protects against challenge. Thus, bacA mutation was a candidate for
      incorporation into live attenuated vaccines. We assessed bacA(mut)-KL7 in 2
      additional mouse strains: the more resistant C57BL/6 that produces interferon
      gamma throughout the infection and the highly susceptible interferon-gamma
      deficient C57BL/6 in which brucellae exhibit continual exponential growth. While
      it was hypothesized that bacA(mut)-KL7 would exhibit even greater attenuation
      relative to its parent strain B. abortus 2308 in C57BL/6 mice than it did in
      BALB/c mice, this was not the case. Moreover, it was more pathogenic in C57BL/6
      interferon-gamma-deficient mice than 2308 causing abscesses and wasting even
      though the splenic loads of bacA(mut)-KL7 were significantly lower. These 2
      observations were correlated, respectively, with an ability of IFNgamma-activated
      macrophages to equivalently control strains 2308 and bacA(mut)-KL7 and the
      ability of bacA(mut)-KL7 organism and its LPS to induce greater amounts of pro
      inflammatory cytokines than 2308. We conclude that attenuation properties of bacA
      mutation are dependent upon the nature of the host but more importantly that
      bacterial gene deletion can result in increased host pathology without an
      increase in bacterial load, crucial considerations for vaccine design.

PMID- 17196867
TI  - Toll-like receptor 2 and Toll-like receptor 4 polymorphisms in invasive
      pneumococcal disease.
AB  - BACKGROUND: Toll-like receptors (TLRs) recognize distinct pathogen-associated
      molecular patterns and trigger anti-microbial host defense responses. Several in
      vitro and in vivo studies in mice indicate that TLR2 and TLR4 are involved in the
      defense against Streptococcus pneumoniae. Studies have revealed associations
      between polymorphisms in TLRs and human diseases. The effect of polymorphisms in
      TLR2 and TLR4 in the human defense to S. pneumoniae has not been studied.
      METHODS: We genotyped 99 Caucasian patients with invasive pneumococcal disease
      and 178 Caucasian controls for the known R579H, P631H and R753Q polymorphisms in
      TLR2 and the D299G polymorphism in TLR4 with PCR-RFLP methods. RESULTS: The
      distribution of the TLR2 R579H, P631H and R753Q and TLR4 D299G variants was not
      significantly different between the patients and the controls. After
      stratification of the patient population by age, sex, diagnosis, and mortality no
      significant differences for the TLR2 R753Q genotype and TLR4 D299G genotype were
      found between various patient subgroups and between patient subgroups and the
      control population. It should be mentioned that for the TLR2 polymorphisms
      neither the control group nor the patient group contains homozygous mutant
      individuals. CONCLUSION: We found no association between TLR2 and TLR4
      polymorphisms and invasive pneumococcal infection.

PMID- 17196868
TI  - Extra-skeletal effects of bisphosphonates.
AB  - Bisphosphonates are pharmacological agents which are currently used both in
      osteoporosis than in other pathological conditions characterised by an increased
      bone resorption, such as Paget's disease of bone, malign hypocalcaemia during
      myeloma, osteolytic bone metastasis and fibrous dysplasia of bone. The most
      important biological effect of bisphosphonates is the reduction of bone
      remodelling through the inhibition of osteoclastic activity, but there are many
      clinical and experimental evidences of extra-skeletal biological effects of
      bisphosphonates. It has been shown that bisphosphonates exert their effects not
      only on bone tissue cells, but also on those of the immune system with an "immuno
      modulating" effect, influencing the production of pro- and anti-inflammatory
      cytokines and changing the molecular expression involved in the immune processes
      and anti-inflammatory response. Although the available data are conflicting,
      there are several reports concerning the beneficial effects of bisphosphonates in
      controlling the progression of chronic joint inflammatory diseases, suggesting a
      wider use for these therapeutic agents in clinical practice.

PMID- 17196869
TI  - [Specific follow-up for pregnant patients with a thyroid dysfunction].
AB  - Association between thyroidian disease and pregnancy is a frequent event.
      Thyroidian hormones are mandatory for foetal development especially at the level
      of brain structures. Any shortage of thyroidian hormone can severely and
      irreversibly alter neurological development. On the other hand it is also clear
      that an excess of thyroidian hormone can jeopardize the embryo then the foetus.
      In case of maternal hyperthyroidism, strict guidelines relying mainly on foetal
      thyroid monitoring echographic scanning will allow in most cases the delivery of
      a healthy euthyroid newborn. Hypothyroidia, providing an adequate substitution,
      has no significant impact on pregnancy. Biological monitoring is the key of
      monitoring. Iodine deficiency is a matter of concern when considering
      neurodevelopmental outcome, however it is still an unsolved issue in France. A
      multidisciplinary team will sometimes be necessary for taking care of pregnant
      patients with active Graves' disease.

PMID- 17196870
TI  - Forensic value of gunpowder tattooing in identification of multiple entrance
      wounds from one bullet.
AB  - Multiple entrance gunshot wounds can give useful information in forensic
      evaluation of deaths from homicide and suicide. Although the presence of multiple
      entrance gunshot wounds does not absolutely exclude the possibility of suicide,
      they are important to the forensic investigators and pathologists in cases of
      assault, attempted homicide and suicide as they provide important clues for
      determination of number of shots fired and direction of firing. We present a case
      of 16 years of young woman who was shot to death by her husband. External
      examination revealed an entrance wound with semi-lunar shot residue at the dorsal
      side of her left hand at 5th metacarpus, and exit wound on the hypothenar muscle.
      There was also a second wound entrance located on her left zygoma. Direction of
      the bullet was downward traveling from left-to-right. Initially it was thought
      that there were two close shots, but when her left hand was placed over the malar
      area her face, it was determined that the gunshot powder tattoos were completing
      the nature of a single shot from a close distance. Crime scene investigation
      revealed only one cartridge casing. The autopsy and radiography findings showed
      that the bullet was entered from dorsal site of the left hand exiting from the
      palm and re-entering from the zygomatic region, hit the base of the skull, and
      remained in the soft tissue of the right mandible after passing the soft palate.
      The bullet was caused an incomplete laceration of the right internal arteria
      carotid and she died of internal and external bleeding. Detailed investigation of
      gunshot residues can provide important information for clarification of close
      distance gunshot wounding. We present this case due to its interesting nature,
      and to highlight the importance of detailed investigation of the gun powder
      residues in cases with multiple entry wounds.

PMID- 17196871
TI  - SPECT imaging, immunohistochemical and behavioural correlations in the primate
      models of Parkinson's disease.
AB  - Dopamine active transporter (DAT) single photon emission computerised tomography
      (SPECT) is considered a useful and practical technique for early diagnosis of
      Parkinson's disease (PD) and assessment of its progression. The application of
      this technique, particularly as a surrogate marker for therapeutic and
      neuroprotective trials in Parkinsonism, however, is dependent on pathological
      validation. In the absence of human studies, we used 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) primate models of Parkinsonism to verify correlation
      between the SPECT, immunohistochemical and behavioural data. The DAT SPECT data
      correlated strongly and significantly with the substantia nigra pars compacta
      tyrosine hydroxylase and Nissl cell counts as well as the behavioural scores.
      Within the limitations of small numbers inherent to such studies, this data
      provides the first attempt at pathological validation of SPECT in primates.

PMID- 17196872
TI  - Clinical-pathologic study of biomarkers in FTDP-17 (PPND family with N279K tau
      mutation).
AB  - The objective of this clinical-pathologic study was to identify biomarkers for a
      pallidopontonigral degeneration (PPND) kindred of frontotemporal dementia and
      parkinsonism linked to chromosome 17 (FTDP-17) harboring the N279K tau mutation.
      Five affected subjects, one at-risk who later became symptomatic, and one at-risk
      asymptomatic mutation carrier, had abnormal (18)fluorodeoxyglucose PET
      demonstrating asymmetric temporal lobe hypometabolism. All except the
      asymptomatic mutation carrier had abnormal brain MRI. Parkinsonism, myoclonus,
      anosmia, insomnia, speech, and autonomic dysfunction were identified. Autopsy of
      six affected subjects showed frontotemporal degeneration with extensive
      tauopathy. Further studies of FTDP-17 patients are needed to replicate these
      findings.

PMID- 17196873
TI  - Munc18a: Munc-y business in mediating exocytosis.
AB  - The precise sequence of molecular events underlying release of neurotransmitter
      in neurons is yet to be fully understood. This process, called exocytosis, is
      tightly controlled by a number of protein-protein and protein-lipid interactions.
      One such regulatory factor is Munc18a, a cytosolic protein characterized by its
      interaction with the molecular machinery of exocytosis, primarily with the target
      SNARE protein, syntaxin1a. While Munc18a interactions have been extensively
      investigated for more than a decade, the role of Munc18a in vesicular fusion is
      still not fully defined. In this review, we discuss: (i) the recent analysis of
      the role of Munc18a in tethering and docking, (ii) the known structural and (iii)
      functional data surrounding Munc18a interactions with numerous other proteins of
      the exocytic machinery. Integration of Munc18a regulation by phosphorylation and
      lipids and the apparent complexity of its pleiotropic functional interactions is
      critical to deciphering Munc18a's role in exocytosis.

PMID- 17196874
TI  - Fibroblasts and myofibroblasts: their source, function and role in disease.
AB  - Fibroblasts are found in most tissues of the body. They exhibit several
      phenotypes including non-contractile fibroblasts, contractile myofibroblasts, and
      intermediate phenotypes including the protomyofibroblast. Fibroblasts are
      metabolically active cells which play critical roles regulating extracellular
      matrices, interstitial fluid volume and pressure, and wound healing. Fibroblast
      numbers can be maintained or expanded by proliferation of resident populations
      but in addition, recent evidence indicates they can also be derived through
      epithelial-mesenchymal transition or from circulating and tissue-derived
      mesenchymal stem cells. Many diseases are associated with dysregulation of the
      injury repair response and fibroblast function, leading to increased or decreased
      deposition of extracellular matrix proteins, altered tissue architecture,
      impaired function and in some cases significant morbidity and mortality. There
      are currently no specific therapies that target fibroblast-associated pathology
      but increasing knowledge of pathological mechanisms has led to development of new
      agents providing hope for improved treatment of these diseases.

PMID- 17196875
TI  - Evaluation of mutagenic activities of leachates in landfill sites by micronucleus
      test and comet assay using goldfish.
AB  - To develop a simple system for monitoring the presence of mutagens/carcinogens in
      the leachates from landfill sites, we used a micronucleus test and a single cell
      gel electrophoresis (comet) assay originally developed for mice and rats on
      goldfish (Carassius auratus). The goldfish were exposed for 9 days to the
      leachate with chemical and biological treatment (treated leachate) or without
      treatment (raw leachate). The goldfish exposed to several samples died because of
      the high concentrations of NaCl or ammonium ion (NH4+). In the comet assay using
      peripheral erythrocytes, the raw leachates showed higher mutagenic activity than
      the treated leachates. In the micronucleus test, it was difficult to detect the
      micronuclei in peripheral erythrocytes. On the other hand, the frequency of
      micronuclei was high in gill cells of goldfish exposed to the raw leachates
      compared to the treated leachates. A combination of the two bioassays was shown
      to be useful to evaluate the mutagenic activity of the leachates. We also propose
      a new scoring method for determination of water quality by using acute toxicity
      and mutagenic activity.

PMID- 17196876
TI  - Debate on annual influenza vaccination in healthcare workers for the same subtype
      under the vaccine shortage.
AB  - BACKGROUND: Influenza vaccination is the primary method for preventing influenza
      and its severe complications. Healthcare workers (HCWs) are one of the priority
      groups for the influenza vaccination. OBJECTIVES: To determine whether healthy
      HCWs, who were vaccinated with the same subtype for the two previous years, could
      be given less priority for influenza immunization under the vaccine shortage.
      STUDY DESIGN: We measured hemagglutination-inhibition antibody titers from
      sequential serum samples in 50 pre-immune subjects and 50 age-matched vaccine
      naive subjects: immediately prior to the administration of the vaccine, 4-6
      weeks, and 6 months after the vaccination. RESULTS: Prevaccination titers were
      maintained above protective level and high protection rates were observed for all
      three strains in pre-immune subjects: A/H1N1, A/H3N2, and B strains. As for the
      sequential changes, the protection rates for all three strains still remained
      above 70% until 6 months following the vaccination. CONCLUSION: Skipping
      influenza vaccination for a year could be considered in healthy pre-immune HCWs
      under the epidemic of the same subtype as two previous years.

PMID- 17196877
TI  - Susceptibility of HIV-1 non-B subtypes and recombinant variants to Enfuvirtide.
AB  - BACKGROUND: Data on susceptibility of HIV-1 non-B subtypes to Enfuvirtide (ENF)
      is rather limited. OBJECTIVE: To determine if ENF could be active in vitro
      against HIV-1 non-B subtypes and how the gp41 genetic variability across variants
      may influence ENF susceptibility. METHODS: Using PHENOSCRIPT Env, a recombinant
      envelope virus assay, ENF susceptibility was investigated in isolates from 19
      drug-naive HIV-1-infected individuals harboring non-B subtypes. RESULTS: Using
      phylogenetic analyses of the gp41 gene, distinct HIV-1 subtypes were recognized:
      A (2), C (5), D (1), F (2), G (1), J (1), CRF02_AG (6) and CRF06 (1).
      Susceptibility to ENF and IC(50) values in vitro could be obtained in only 13
      (68.4%) specimens, most likely due to the high genetic variability in HR1 and HR2
      regions in the remaining cases. A wide range of IC(50) values with a median of
      0.013 microg/ml was observed (range, 0.005-0.180 microg/ml). Natural
      polymorphisms, but not classical ENF resistance associated mutations within HR1
      (residues 36-45) were identified in most non-B viruses. CONCLUSION: This study
      provides information about the baseline susceptibility to ENF in antiretroviral
      naive subjects infected with different HIV-1 non-B subtypes. Susceptibility to
      ENF seems to be preserved despite high genetic variability in HR1 and HR2
      regions.

PMID- 17196878
TI  - Conjugated EPA activates mutant p53 via lipid peroxidation and induces p53
      dependent apoptosis in DLD-1 colorectal adenocarcinoma human cells.
AB  - Both conjugated linoleic acid (CLA), which contains conjugated double bonds, and
      eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, have antitumor
      effects. Hence, we hypothesized that a combination of conjugated double bonds and
      an n-3 highly unsaturated fatty acid may produce a stronger antitumor effect, and
      we have previously shown that conjugated EPA (CEPA), prepared by alkaline
      treatment of EPA, induces strong and selective apoptosis in vitro and in vivo,
      with the mechanism proceeding via lipid peroxidation. In this study, we examined
      CEPA-induced gene expression in DLD-1 colorectal adenocarcinoma human cells
      carrying a mutant p53, in order to understand the details of CEPA-induced
      apoptosis via lipid peroxidation. DNA microarray analysis of 9970 genes was
      performed by comparison of CEPA-treated DLD-1 cells with untreated DLD-1 cells,
      thereby allowing determination of the differential gene expression profile
      induced by CEPA in these cells. CEPA treatment caused up-regulation of expression
      of genes induced by p53 and activation of the mitochondrial apoptosis pathway via
      Bax and the death pathway via TRAIL, leading to apoptosis of DLD-1 cells. In
      addition, activation of the mutant p53 was also induced by CEPA, and these
      effects showed lipid-peroxidation dependency. This is the first such gene
      expression analysis of the effects of CEPA, and our results confirm that CEPA
      induces lipid peroxidation, activates mutant p53, and causes p53-dependent
      apoptosis in DLD-1 cells.

PMID- 17196879
TI  - Analysis of environmental 18S ribosomal RNA sequences reveals unknown diversity
      of the cosmopolitan phylum Telonemia.
AB  - Telonemia has recently been described as a new eukaryotic phylum with uncertain
      evolutionary origin. So far, only two Telonemia species, Telonema subtilis and
      Telonema antarcticum, have been described, but there are substantial variations
      in size and morphology among Telonema isolates and field observations, indicating
      a hidden diversity of Telonemia-like species and populations. In this study, we
      investigated the diversity and the global distribution of this group by analyzing
      18S rDNA sequences from marine environmental clone libraries published in GenBank
      as well as several unpublished sequences from the Indian Ocean. Phylogenetic
      analyses of the identified sequences suggest that the Telonemia phylum includes
      several undescribed 18S rDNA phylotypes, probably corresponding to a number of
      different species and/or populations. The Telonemia phylotypes form two main
      groups, here referred to as Telonemia Groups 1 and 2. Some of the closely related
      sequences originate from separate oceans, indicating worldwide distributions of
      various Telonemia phylotypes, while other phylotypes seem to have limited
      geographical distribution. Further investigations of the evolutionary
      relationships within Telonemia should be conducted on isolated cultures of
      Telonema-like strains using multi-locus sequencing and morphological data.

PMID- 17196880
TI  - Use of temporary epicardial pacing wires in cardiac surgery.

PMID- 17196881
TI  - Late restenosis following placement of a sirolimus eluting stent for in-stent
      restenosis.
AB  - Drug eluting stents (DES) are rapidly replacing intravascular brachytherapy for
      the treatment of bare metal in-stent restenosis (ISR). To date, there are no long
      term follow up data supporting this practise. We report symptomatic repeat in
      stent restenosis occurring 27 months after sirolimus eluting stent deployment for
      de novo in-stent restenosis. This case suggests that in a subgroup of patients
      with ISR, as with brachytherapy, the drug eluting stent may be simply delaying
      rather than inhibiting the restenotic process.

PMID- 17196882
TI  - The stability of mRNA encoding IL-4 is increased in pulmonary tuberculosis, while
      stability of mRNA encoding the antagonistic splice variant, IL-4delta2, is not.
AB  - The prototype Th2 cytokine IL-4, and its competitive antagonist IL-4delta2, may
      be important determinants of outcome in human tuberculosis (TB). However, there
      are no data on how gene expression of these cytokines is regulated. To evaluate
      this the stability of IL-4 and IL-4delta2 mRNA after the addition of actinomycin
      D, was evaluated in whole blood from subjects with pulmonary TB and uninfected
      healthy volunteers. The Th2/Th1 (IL-4/IFN-gamma) mRNA ratio in unstimulated cells
      in whole blood was significantly greater in TB subjects than in controls
      (p<0.05). The mRNA half-life of the agonist (IL-4), but not the antagonist (IL
      4delta2), was significantly prolonged in subjects with TB compared to healthy
      volunteers ( approximately 5-fold, p=0.0016), and the IL-4/IL-4delta2 ratio was
      higher in TB patients compared to controls (p<0.05). The differential stability
      of the Th2 agonist, IL-4, compared to the antagonist IL-4delta2, represents a
      hitherto undescribed post-transcriptional regulatory mechanism that may modulate
      the polarisation of Th1/Th2 responses in human TB.

PMID- 17196883
TI  - Depressive behavior and selective down-regulation of serotonin receptor
      expression after early-life seizures: reversal by environmental enrichment.
AB  - Depression is the most common psychiatric comorbidity in epilepsy. To better
      understand the contribution of seizures versus environment to depression in
      epilepsy, we investigated differential gene expression using microarray and
      quantitative RT-PCR, and depressive behavior, in the Porsolt forced swim test in
      juvenile rats reared in different environments after kainic acid (KA)-induced
      seizures. We selected for genes significantly down-regulated by KA seizures and
      upregulated by environmental enrichment. This common gene selection process
      yielded one known gene involved in mood and affect: serotonin receptor 5B. The
      changes in serotonin receptor gene expression were paralleled by decreased
      mobility in the forced swim tests; depressive behavior exhibited after seizures
      was no longer evident in rats reared in environmental enrichment. Our results
      suggest that seizures lead to increased susceptibility to depression through
      transcriptional regulation while environment, in turn, can interact with gene
      expression to influence the behavioral outcome of epilepsy.

PMID- 17196884
TI  - Sudden unexpected death in epilepsy: a search for risk factors.
AB  - Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure
      related mortality in people with refractory epilepsy. Of the 6140 patients
      registered with the Epilepsy Unit at the Western Infirmary in Glasgow between
      1982 and 2005, 529 had died, 62 (11.7%) of whom succumbed to SUDEP. All but 2
      deaths occurred at home; 3 were witnessed. Two living controls were matched with
      each SUDEP case for year of birth, gender, and syndromic classification. Mean
      duration of epilepsy was significantly longer in cases compared with controls
      (P=0.001). More people succumbing to SUDEP had had a seizure within the previous
      year (P=0.007). There were no significant associations between SUDEP and a
      history of generalized tonic-clonic seizures, drug polytherapy, and current use
      of carbamazepine. There is an urgent need for a large-scale, prospective,
      international, community-based study of SUDEP to explore more closely the risk
      factors to plan preventive strategies.

PMID- 17196885
TI  - Sublethal copper exposure induces respiratory stress in common and gibel carp but
      not in rainbow trout.
AB  - Rainbow trout, common carp, and gibel carp were exposed to sublethal Cu levels
      (1.0 or 1.7 microM) for 1 week. In rainbow trout, arterial oxygen tension
      (P(aO(2))) remained normal and there was no indication of anaerobic metabolism.
      P(aO(2)) was considerably lower in common and gibel carp and Cu exposure
      decreased this further. The decrease was transient for common carp but persistent
      in gibel carp and coincided with an elevation in arterial carbon dioxide tension
      (P(aCO(2))) indicating that all gas exchange was compromised in both cyprinid
      species. The disturbed gas exchange resulted in acidosis, which was respiratory
      and metabolic for common carp but mainly respiratory for gibel carp. Gibel carp
      produced ethanol as end product of their alternative anaerobic pathway. The
      hypothesis that hypertrophy and hyperplasia, resulting in increased diffusion
      distances, are reducing P(aO(2)) appeared invalid. Hypoventilation seems a more
      likely cause. Ionoregulatory parameters responded more uniform among species.
      Fast and pronounced decreases in plasma sodium and chloride developed for all
      three species, independent of the observed gill damage. Rainbow trout lost 20% of
      their plasma Na in the first 3 days, while common and gibel carp had only lost 13
      and 16% respectively at that time. This difference might be crucial when
      challenged with Cu exposure and allow a fish to survive the first shock phase and
      supports it the hypothesis that sodium turnover is a key factor in predicting Cu
      toxicity.

PMID- 17196886
TI  - Does starvation influence the antioxidant status of the digestive gland of
      Nacella concinna in experimental conditions?
AB  - In a previous study we analysed the effect of diesel seawater contamination in
      the digestive gland of the Antarctic limpet Nacella concinna. We observed that
      antioxidant enzyme activities decreased after one-week starvation prior to the
      experiment, and this was considered in the analysis of the obtained results. To
      know whether the digestive gland oxidant-antioxidant status may be altered by
      starvation and experimental conditions, we evaluated the food deprivation effect
      in limpets from the nearshore shallow waters of Potter Cove, Antarctica.
      Organisms were acclimated to laboratory conditions and were divided in fed and
      starved groups, and maintained in these conditions during one month. Every week
      20 limpets were sampled from each group. Digestive glands were dissected and kept
      frozen until they were processed. Superoxide dismutase (SOD), catalase (CAT) and
      glutathione S-transferase (GST) activities, as well as lipid peroxidation (LPO)
      measured as thiobarbituric reactive substances (TBARS), protein oxidation (PO)
      and reduced glutathione (GSH) were measured. For both groups of limpets, SOD
      increased its activity in the first week of the exposure period, with a maximum
      in the second week. CAT activity increased significantly in the second week, only
      for the starved group. Similarly, GST activity also increased for starved group
      in the second week; but maintained this tendency for both groups until the fourth
      week. In fed and starved limpets, TBARS values increased significantly, during
      the first week and then returned to normal values. The PO levels in the starved
      group increased only during the first week. The GSH content, for the fed group,
      increased significantly after the third week. The obtained results indicate that
      biochemical or physiological studies conducted with N. concinna should consider
      the effects of food deprivation and time spent under experimental conditions.

PMID- 17196887
TI  - Effects of Astragalus membranaceus and its main components on the acute phase
      endothelial dysfunction induced by homocysteine.
AB  - OBJECTIVE: This study was designed to investigate the effects of Astragalus
      membranaceus (AM) and its main components, astragalus saponin (ASP), astragalus
      polysaccharide (APS) and aminobutyric acid (GABA), on homocysteine (Hcy) induced
      acute impairment of vascular tone and to explore whether the antioxidant
      mechanism was involved in AM protective effect. METHODS: Inhibitory effects of
      Hcy and protective effects of AM and its main components on endothelium-dependent
      relaxation of aortic rings were determined by isometric tension recordings and
      nitric oxide signaling was assayed with 125I-cGMP RIA Kit. Furthermore,
      generation of reactive oxygen species (ROS) in endothelial cells was detected
      using 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCF
      DA). RESULTS: Hcy significantly inhibited endothelium-dependent relaxation to
      acetylcholine (ACh) in a dose-dependent manner, and decreased cGMP levels
      increased by ACh in aorta. Furthermore, superoxide dismutase (SOD), AM, and ASP
      markedly attenuated inhibition of vasorelaxation and downregulation of cGMP level
      by Hcy, and APS exerted a tendency to reverse both of the depressive responses,
      while GABA had no similar effects. Additionally, partially impaired relaxation by
      Hcy was completely blocked due to the presence of N(omega)-nitro-L-arginine
      methyl ester (L-NAME), which could not be further altered by treatment with AM,
      ASP, APS or GABA. Finally, Hcy significantly increased intracellular ROS levels
      in endothelial cells as measured by CM-H2DCF-DA fluorescence. SOD, AM, ASP, and
      APS, but not GABA, inhibited Hcy-stimulated ROS generation. CONCLUSION: This
      study demonstrated that AM and ASP, potently protected endothelium-dependent
      relaxation against the acute injury from Hcy through nitric oxide regulatory
      pathways, in which antioxidation played a key role.

PMID- 17196888
TI  - The role of the consent document in informed consent for pediatric leukemia
      trials.
AB  - PURPOSE: To examine both the use of the consent document during the informed
      consent process for pediatric leukemia clinical trials, as well as relationships
      between the use of the document and parental understanding of essential elements
      of informed consent. METHODS: Participants included 140 parents of children
      diagnosed with pediatric leukemia. Informed consent conferences in which
      randomized clinical trials were discussed were observed, audiotaped, and coded
      for specific behaviors. Parents were also interviewed within 48 h of their
      participation in informed consent conferences. RESULTS: Observations revealed
      that 74% of cases included explanation of consent documents during consent
      conferences. Parents who reported that they read the consent document were more
      likely to understand differences between the clinical trial and off study therapy
      and were more likely to understand the right to withdraw. Reading of the consent
      document was not associated with understanding of voluntariness. In comparison to
      racial/ethnic majority parents, racial/ethnic minority parents were less likely
      to report that they read the consent document, understand voluntariness or the
      right to withdraw, and were less likely to be able to distinguish between the
      clinical trial and off study therapy. Low SES was associated with a lower
      probability of reading the consent document and being able to distinguish between
      clinical trials and off study therapy. CONCLUSIONS: Attention to the importance
      of reading the consent document and improving communication during consent
      conferences is likely to enhance understanding of essential elements of informed
      consent.

PMID- 17196889
TI  - Exercise training improves arterial baro- and chemoreflex in control and diabetic
      rats.
AB  - We investigated the effect of exercise training on blood pressure, heart rate,
      and arterial baro- and chemoreflex sensitivity in diabetic rats (streptozotocin,
      50 mg/kg iv). Male Wistar rats (251+/-10 g) were divided into 4 groups (n=8, each
      group): sedentary normotensive (SC), sedentary diabetic (SD), trained
      normotensive (TC), and trained diabetic (TD). Trained groups underwent exercise
      training on a treadmill (10 weeks). Exercise training induced resting bradycardia
      (340+/-5 vs. 316+/-8 bpm) and improvement in baroreflex tachycardic response
      (3.4+/-0.31 vs. 2.7+/-0.06 bpm/mmHg in SC) and chemoreflex bradycardic (145+/-12
      vs. 78+/-7 bpm in SC) and pressor (49+/-5 vs. 22+/-3 mmHg in SC) responses in
      control rats. Diabetic-induced hypotension (SC: 107+/-2 vs. SD: 93+/-2 mmHg) and
      bradycardia (SC: 340+/-5 vs. SD: 276+/-7 bpm) were reversed by exercise training.
      Baroreflex tachycardic and bradycardic responses impaired in SD rats (SD: 2.1+/
      0.18 and 1.3+/-0.08 vs. SC: 2.7+/-0.06 and 1.3+/-0.08 bpm/mmHg) were enhanced in
      TD rats (2.5+/-0.1 and 1.7+/-0.06 bpm/mmHg). Chemoreflex bradycardic and pressor
      responses, attenuated in SD rats (23+/-9 bpm and 7+/-1 mmHg) in relation to SC
      rats, were improved by exercise (TD: 84+/-15 bpm and 32+/-5 mmHg). The
      improvement in arterial baro- and chemoreflex-mediated control of circulation in
      trained control and diabetic rats reinforces the role of exercise in the
      management of cardiovascular risk in healthy and diabetic individuals.

PMID- 17196890
TI  - Cardiovascular effects of centrally applied endothelin-1 1-31 and its
      relationship to endothelin-1 1-21 in rats.
AB  - Endothelin-1(1-31) (ET-1(1-31)) is a novel member of the endothelin family, which
      comprises 31 amino acids and derived from the selective hydrolysis of big ET-1 by
      chymase. Although ET-1(1-31) has been reported to be involved in biological
      effects via direct or indirect (converting to ET-1(1-21)) mechanisms, the
      cardiovascular effects of central ET-1(1-31) are not fully identified. The
      present study was designed to comparatively investigate the cardiovascular
      effects of intracerebroventricular (icv) application of ET-1(1-31) or ET-1(1-21)
      in anesthetized rats. Injection (icv) of ET-1(1-31) (500 pmol) produced a
      biphasic blood pressure response: an initial increase (from 118+/-8 to 138+/-14
      mmHg, P<0.05) followed by a sustained decrease in BP (from 118+/-8 to 58+/-9
      mmHg, P<0.05), which was very similar to BP response to icv injection of big ET-1
      (500 pmol) or ET-1(1-21) (25 pmol)(.) The cardiovascular effects of icv injection
      of ET-1(1-31) or ET-1(1-21) were completely antagonized by ET(A) receptor
      antagonist BQ123 but not ET(B) receptor antagonist BQ788. Furthermore,
      pretreatment with ET converting enzyme inhibitor phosphoramidon (10 nmol)
      abolished the cardiovascular effects evoked by icv injection of ET-1(1-31) or big
      ET-1. In conclusion, the current data showed that central ET-1(1-31) produced the
      similar cardiovascular effects as those of central ET-1(1-21), and suggesting
      that the central cardiovascular effects of ET-1(1-31) resulted from it converting
      to ET-1(1-21) and then activating ET(A) receptors.

PMID- 17196891
TI  - A new high performance liquid chromatographic method for quantification of
      atomoxetine in human plasma and its application for pharmacokinetic study.
AB  - Atomoxetine is the first, non-stimulant alternative to other stimulant
      medications used for the treatment of Attention-Deficit/Hyperactivity Disorder
      (ADHD). Reported methods for the determination of atomoxetine include expensive
      liquid chromatography tandem mass spectrometry (LCMS) and high performance liquid
      chromatography (HPLC) with liquid scintillation counting (LSC) detection. Till
      date, no method has been reported in literature to determine atomoxetine using
      HPLC with UV detection. In this paper, we describe a new HPLC method for the
      determination of atomoxetine using liquid-liquid extraction with tertiary butyl
      methyl ether and UV detector. This method was found to be linear over the
      concentration range of 0.05-3.0 microg/ml. The limit of quantification was 0.05
      microg/ml. Intra- and inter-day precision was <15% and accuracy was in the range
      of 95.67-108.80%. Stability studies showed that atomoxetine was stable in human
      plasma for short- and long-term period for sample preparation and analysis. This
      method was used for sample analysis in a pharmacokinetic study of atomoxetine
      (25mg) in five healthy adult female volunteers. The observed mean+/-S.D.
      pharmacokinetic parameters Cmax, Tmax and AUC(0-t) were 0.40+/-0.06 microg/ml,
      3.40+/-0.42 h and 1.34+/-0.52 microg h/ml, respectively.

PMID- 17196892
TI  - Childcare, height and BMI among female Polish university students, 2005.
AB  - The aim of this study is to consider whether socio-economic factors are related
      to the type of childcare and whether the type of childcare, in turn, affects
      adult stature and BMI. The sample includes 783 female students aged 20-24 (birth
      cohort of 1981-1985) from the south of Poland. Those whose parents have
      university education, live in a city and have no siblings attend day-care
      facilities more frequently than others of the same age, while those who grew up
      at home under their mothers' care, most frequently live in villages, come from
      large families and their parents have vocational education. Variables which are
      associated with being taller include material conditions and the type of
      childcare received. Women who had attended day-care centres are 2.4cm shorter
      than girls brought up at home by their mothers. Adult BMI values are influenced
      by educational level of the mother. The results suggest that mothers who work
      often do so at the cost of time devoted to the family which influences health and
      the rate of their children's development.

PMID- 17196893
TI  - Clinical outcome of patients examined by capsule endoscopy for suspected small
      bowel Crohn's disease.
AB  - BACKGROUND: Capsule endoscopy has a greater diagnostic yield than radiology for
      detecting subtle inflammatory changes of the small bowel mucosa, but the clinical
      significance of these abnormalities is still uncertain because of the lack of
      long-term follow-ups. AIM AND METHODS: To verify the accuracy of capsule
      endoscopy in a cohort of patients with suspected Crohn's disease of the small
      bowel, taking as 'gold standard' the final diagnosis made after a long follow-up.
      From April 2002 to March 2005, we enrolled and examined by capsule endoscopy 27
      consecutive patients with abdominal pain and diarrhea lasting more than 3 months
      and at least one of the following: anaemia, weight loss, fever, extra-intestinal
      manifestation(s) of inflammatory bowel disease. All patients already had an
      unremarkable pan-endoscopy, serology for celiac disease and intestinal radiology
      inconclusive for small bowel abnormality. On the basis of capsule endoscopy
      findings, patients were distributed in three groups; Group A had severe
      stricturing lesions requiring surgery; Group B, moderate inflammatory lesions
      further investigated invasively; Group C, minimal inflammatory changes or normal
      findings, clinically observed every 3 months (median 21 months, range 15-29).
      RESULTS: Small bowel inflammatory lesions were found in 16 of the 27 patients
      (diagnostic yield 59%). Three had surgery (Group A) and Crohn's disease was
      confirmed in two; the remainder had ileal adenocarcinoma in a pathological
      context of chronic inflammation. Crohn's disease was histologically confirmed in
      four of the five patients in Group B. Group C comprised 19 patients; Crohn's
      disease was confirmed in seven out of eight with positive capsule endoscopy,
      while only one of the patients with normal findings later developed overt ileal
      Crohn's disease. Sensitivity, specificity, positive and negative likelihood ratio
      were, respectively, 93%, 84%, 5.8 and 0.08. Assuming a 50% pre-test probability
      of disease, capsule endoscopy gave a post-test probability of 85%. CONCLUSIONS:
      In our selected cohort, capsule endoscopy was highly sensitive in detecting small
      bowel inflammatory changes, enhancing by nearly 35% the pre-test probability of
      structural small bowel disease. Focal erythema and luminal debris may limit the
      specificity of capsule endoscopy.

PMID- 17196894
TI  - The transjugular route: the key hole to the liver world.
AB  - Portal hypertensive complications are major causes of morbidity and mortality in
      patients with liver cirrhosis. The advent of the transjugular route with its
      minimal access allows non-surgical management of portal hypertension, therapy of
      venous complications of liver transplantation, monitoring of therapy for portal
      hypertension, hepatic venous pressure gradient and is also the major route to
      treat hepatic venous obstruction syndromes. In addition, the transjugular route
      is a safe route to perform a liver biopsy (transjugular liver biopsy) and allows
      retrograde evaluation of the portal vein. All these procedures can be combined in
      the same session. These hepatic interventional radiological skills should be
      incorporated into the expertise of the liver team in specialised hepatological
      centres, particularly in liver transplant centres as they are especially useful
      in improving outcomes of cirrhotic patients on the liver transplantation waiting
      list. A limitation in achieving this goal, could be the number of experienced
      radiologists, but hepatologists can be trained, at least for the most simple
      procedures (transjugular liver biopsy and hepatic venous pressure gradient). This
      would allow wider applicability and use of these diagnostic and therapeutic
      techniques, all through a 2 mm hole in the neck--the key hole to the liver world.

PMID- 17196895
TI  - DU145 human prostate cancer cells express functional receptor activator of
      NFkappaB: new insights in the prostate cancer bone metastasis process.
AB  - Prostate cancer metastases to bone are observed in around 80% of prostate cancer
      patients and represent the most critical complication of advanced prostate
      cancer, frequently resulting in significant morbidity and mortality. As the
      underlying mechanisms are not fully characterized, understanding the biological
      mechanisms that govern prostate cancer metastases to bone at the molecular level
      should lead to the determination of new potential therapeutic targets. Receptor
      activator of NFkappaB ligand (RANKL)/RANK/Osteoprotegerin (OPG) are the key
      regulators of bone metabolism both in normal and pathological condition,
      including prostate cancer bone metastases. In the present study, we demonstrated
      that human prostate cancer cell lines, DU145 and PC3 express biologically
      functional RANK. Indeed, soluble human RANKL (shRANKL, 100 ng/ml) treatment
      induced ERK 1/2, p38 and IkappaB phosphorylations in these cells. shRANKL
      administration also promoted DU145 and PC3 prostate cancer cell invasion in
      vitro. Whereas human OPG (hOPG) administration alone (100 ng/ml) had no marked
      effect, combined association of both agents abolished the RANKL-induced DU145
      cell invasion. As RANKL had no direct effect on DU145 cell proliferation, the
      observed effects were indeed related to RANKL-induced cell migration. DU145 human
      prostate cancer cells promoted osteoclastogenesis of osteoclast precursors
      generated from mouse bone marrow. Moreover, DU145 cells produced soluble
      factor(s) that up-regulate the proliferation of MC3T3-E1 pre-osteoblasts through
      the activation of the ERK 1/2 and STAT3 signal transduction pathways. This
      stimulation of pre-osteoblast proliferation resulted in an increased local RANKL
      expression that can activate both osteoclasts/osteoclast precursors and prostate
      cancer cells, thus facilitating prostate cancer metastasis development in bone.
      We confirm that RANKL is a factor that facilitates metastasis to bone by acting
      as an activator of both osteoclasts and RANK-positive prostate cancer cells in
      our model. Furthermore, the present study provides the evidence that blocking
      RANKL-RANK interaction offer new therapeutic approach not only at the level of
      bone resorbing cells, but also by interfering with RANK-positive prostate cancer
      cells in the prostate cancer bone metastasis development.

PMID- 17196896
TI  - Trauma care--a team sport in the 21st century.

PMID- 17196897
TI  - Proceedings of Ultrasonics International (UI'05) and World Congress on
      Ultrasonics (WCU), Beijing, China, 29 August-01 September 2005.

PMID- 17196898
TI  - Opioids in patients on renal dialysis.

PMID- 17196899
TI  - Successful use of ketamine infusion in the treatment of intractable cancer pain
      in an outpatient.

PMID- 17196900
TI  - Failure of pain control using transdermal fentanyl during rifampicin treatment.

PMID- 17196901
TI  - Need for better documentation and definition of pain flare following external
      beam radiotherapy in the treatment of bone metastases.

PMID- 17196902
TI  - Palliative care philosophies of Japanese certified palliative care units: a
      nationwide survey.

PMID- 17196903
TI  - Evaluation of the functional assessment of cancer therapy cognitive scale with
      hematopoietic stem cell transplant patients.
AB  - The current study evaluated a newly developed self-report measure of cognitive
      complaints with cancer patients, the Functional Assessment of Cancer Therapy
      Cognitive Scale (FACT-Cog). Six or 12 months following hematopoietic stem cell
      transplantation, participants completed a psychosocial assessment that included
      the FACT-Cog and a neuropsychological assessment. Using a criterion of two or
      more times a week, an average of 12 of a total of 50 items were endorsed as
      complaints on the FACT-Cog. FACT-Cog total, domain, and subscale scores were
      significantly correlated with measures of depression, fatigue, anxiety, and
      physical and mental well-being. FACT-Cog scores, with the exception of one
      subscale, Other People Noticed Deficits, were not significantly correlated with
      cognitive performance. In general, the FACT-Cog and a commonly used measure of
      cognitive complaints (European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire-C30 Cognitive Functioning Scale) demonstrated
      similar psychometric properties. However, the FACT-Cog assesses broader aspects
      of cognitive complaints, thereby providing greater information about the types of
      cognitive complaints patients are experiencing.

PMID- 17196904
TI  - Pain management in the last six months of life among women who died of ovarian
      cancer.
AB  - Previous studies indicate that the symptoms of many dying cancer patients are
      undertreated and many suffer unnecessary pain. We obtained data retrospectively
      from three large health maintenance organizations, and examined the analgesic
      drug therapies received in the last six months of life by women who died of
      ovarian cancer between 1995 and 2000. Subjects were identified through cancer
      registries and administrative data. Outpatient medications used during the final
      six months of life were obtained from pharmacy databases. Pain information was
      obtained from medical charts. We categorized each medication based on the World
      Health Organization classification for pain management (mild, moderate, or
      intense). Of the 421 women, only 64 (15%) had no mention of pain in their charts.
      The use of medications typically prescribed for moderate to severe pain ("high
      intensity" drugs) increased as women approached death. At 5-6 months before
      death, 55% of women were either on no pain medication or medication generally
      used for mild pain; only 9% were using the highest intensity regimen. The
      percentage on the highest intensity regimen (drugs generally used for severe
      pain) increased to 22% at 3-4 months before death and 54% at 1-2 months. Older
      women (70 or older) were less likely to be prescribed the highest intensity
      medication than those under age 70 (44% vs. 70%, P<0.001). No differences were
      found in the use of the high intensity drugs by race, marital status, year of
      diagnosis, stage of disease, or comorbidity. Our finding that only 54% of women
      with pain were given high intensity medication near death indicates room for
      improvement in the care of ovarian cancer patients at the end of life.

PMID- 17196905
TI  - Mood state and quality of sleep in cancer pain patients: a comparison to chronic
      daily headache.
AB  - Cancer pain is commonly believed to be a unique type of pain and dissimilar to
      noncancer pain; however, only limited research efforts have been directed at
      examining this belief. The aim of this study was to explore whether patients with
      chronic daily headache (CDH) and patients with chronic cancer pain (CCP) present
      with different pain, mood, and sleep quality profiles. Forty-seven patients
      diagnosed with CDH were matched by age and gender with 47 patients with CCP. The
      research instruments included the Brief Pain Inventory-Chinese version, the
      Profile of Mood States Short Form, and the Pittsburgh Sleep Quality Index-Taiwan
      Form (PSQI-T). Results revealed that there was no difference in pain intensity
      between the patients with CDH and those with CCP; however, the CCP group reported
      significantly higher mean levels of pain interference with daily life than did
      the CDH group. These two groups did not differ on the Total Mood Disturbance
      score; however, the CCP group reported significantly lower mean levels of vigor
      than did the CDH group. Moreover, there was no difference on the PSQI-T total
      score between these two groups; however, the CDH group reported higher mean
      scores of sleep disturbance, higher mean scores of use of sleep medications,
      lower mean scores of sleep efficiency, and lower mean scores of daytime
      dysfunction than did the CCP group. Despite some differences between these two
      groups, pain, mood, and sleep quality profiles in these two types of pain groups
      are similar.

PMID- 17196906
TI  - Transforming doctor-patient relationships to promote patient-centered care:
      lessons from palliative care.
AB  - Palliative care was studied for its potential to yield lessons for transforming
      doctor-patient relationships to promote patient-centered care. Examination of
      patient and provider experiences of the transition from curative to palliative
      care promises valuable insights about establishing and maintaining trust as the
      goals of care shift and about addressing a broad spectrum of patient needs. The
      study was guided by a conceptual framework grounded in existing models to address
      five dimensions of doctor-patient relationships: range of needs addressed, source
      of authority, maintenance of trust, emotional involvement, and expression of
      authenticity. Data collection included observation of the care of 40 patients in
      the inpatient hospice unit and at home, interviews with patients and family
      members, and in-depth interviews with 22 physicians and two nurses providing end
      of-life care. Standard qualitative procedures were used to analyze the data,
      incorporating techniques for maximizing the validity of the results and
      broadening their relevance to other contexts. Findings provide evidence for
      challenging prominent assumptions about possibilities for doctor-patient
      relationships: questioning the merits of the prohibition on emotional
      involvement, dependence on protocols for handling difficult communication issues,
      unqualified reliance on consumer empowerment to assure that care is responsive to
      patients' needs, and adoption of narrowly defined boundaries between medical and
      social service systems in caring for patients. Medical education can play a role
      in preparing doctors to assume new roles by openly addressing management of
      emotions in routine clinical work, incorporating personal awareness training,
      facilitating reflection on interactions with patients through use of standardized
      patients and videotapes, and expanding capacity to effectively address a broad
      range of needs through teamwork training.

PMID- 17196907
TI  - The association of symptoms with health outcomes in chronically ill adults.
AB  - Persons with chronic disease experience multiple symptoms. Understanding the
      association between these symptoms and health outcomes would facilitate a
      targeted approach to symptom assessment and treatment. Our objectives were to
      determine the association of a range of symptoms with quality of life, self-rated
      health, and functional status among chronically ill adults, and to assess methods
      for evaluating the independent associations of symptoms that may be interrelated.
      We consecutively enrolled 226 cognitively intact, community-dwelling adults, aged
      60 years or older with chronic obstructive pulmonary disease, heart failure, or
      cancer. Seven symptoms (physical discomfort, pain, fatigue, problems with
      appetite, feelings of depression, anxiety, and shortness of breath) assessed
      using the Edmonton Symptom Assessment Scale were examined for their association
      with self-rated quality of life, self-rated health, and functional status.
      Principal component analysis and logistic regression revealed similar results.
      The latter demonstrated that physical discomfort was associated with lower self
      rated health (adjusted odds ratio [OR] 1.9; 95% confidence interval 1.2-2.9) and
      functional disability (adjusted OR 1.8; 95% confidence interval 1.2-2.7).
      Feelings of depression were associated with poorer quality of life (adjusted OR
      1.7; 95% confidence interval 1.1-2.6), and shortness of breath was associated
      with lower self-rated health (adjusted OR 1.5; 95% confidence interval 1.1-2.0).
      The association between a range of symptoms and quality of life, self-rated
      health, and functional status differed across outcomes, but only three symptoms
      physical discomfort, feelings of depression, and shortness of breath-maintained
      their associations when multiple symptoms were examined concurrently. These
      findings suggest that interventions targeting these symptoms could improve
      several health-related outcomes.

PMID- 17196908
TI  - Differences in the prevalence and severity of side effects based on type of
      analgesic prescription in patients with chronic cancer pain.
AB  - An understanding of the relationship between the type of analgesic prescription
      and the prevalence and severity of side effects is crucial in making appropriate
      treatment decisions. The purposes of this study were to determine if there were
      differences in the prevalence of side effects among four different types of
      analgesic prescriptions (i.e., no opioid, only an as needed (PRN) opioid, only an
      around-the-clock (ATC) opioid, or an ATC+PRN opioid); to determine if there were
      differences in the severity of side effects among the four prescription groups;
      and to determine the relationships between the total dose of opioid analgesic
      medication prescribed and taken and the severity of side effects. As part of a
      larger study, 174 cancer patients with bone metastasis reported their analgesic
      use and the prevalence and severity of 11 side effects. Significant differences
      (P<0.05) were found in prevalence rates for seven of the side effects among the
      four prescription groups. The highest prevalence rates were found in the only ATC
      and ATC+PRN groups. Significant differences were found in the severity scores for
      five of the side effects, with the highest severity scores reported by patients
      in the only ATC and ATC+PRN groups. Significant positive correlations were found
      between the severity of six of the side effects and the total dose of opioid
      prescribed and taken. Risk factors for analgesic-induced side effects are ATC and
      ATC+PRN prescription types and higher doses of opioid analgesics.

PMID- 17196909
TI  - Cognitive function impairment in patients with neuropathic pain under standard
      conditions of care.
AB  - The objective of this study is to analyze the prevalence to cognitive function
      impairment (CI) in a pragmatic cohort of subjects with different types of
      neuropathic pain under standard conditions of care by means of a cross-sectional
      baseline analysis of a sample of patients with NeP enrolled in a pragmatic,
      prospective, multicenter study evaluating the effectiveness of gabapentin. A
      total of 1519 patients (58.8% women), aged > or =18 years (mean [SD]=56.0
      [13.7]), with neuropathic or mixed neuropathic and nociceptive pain for a mean
      (SD) of 1.1 (2.8) years were enrolled in the study. Pain was assessed with the
      short form of the McGill Pain Questionnaire, and cognitive function was measured
      with the Mini-Mental State Examination (MMSE). A score < or =24 on the MMSE was
      considered as CI. Multivariate logistic regression models were used to estimate
      CI prevalence. CI prevalence was substantially higher in patients with NeP than
      that reported in the general Spanish population, and significantly higher than in
      patients with mixed neuropathic and nociceptive pain: 11.4% (8.5%-14.3%) vs. 6.4%
      (4.6%-8.7%), P=0.006 (adjusted odds ratio=1.88 [1.21-2.91]). Prevalence
      significantly increased with age, up to 32.2% (20.6%-45.6%) in those with NeP,
      and to 28.2% (15.0%-44.9%) in those with mixed syndromes, for the age group > or
      =75 years, P<0.001 within age groups. Symptoms of anxiety and obesity, and to a
      lesser extent, symptoms of depression, were also factors associated with a higher
      prevalence rate of CI. This analysis showed that, after adjusting for confounding
      factors, the prevalence of CI was substantially higher in patients with NeP than
      those with mixed pain and the reference general population. Age, anxiety,
      depression, and obesity were factors found to be significantly associated with
      CI.

PMID- 17196910
TI  - Hospice partnerships with academic entities: philosophical and historical
      background and assessment of future needs.
AB  - There is consensus that more research is needed to help improve care at the end
      of life. Despite the fact that hospices take care of more and more dying persons
      every year, hospice organizations have not been highly involved in research. The
      National Hospice Work Group is comprised of hospice organizations that have made
      promotion of research a high priority. Structured interviews were conducted with
      members of the National Hospice Work Group to investigate how they think about
      the role of academic partners in their organizational missions, what their
      histories of involvement with academic partners are, and what they see as their
      most important academic needs for continuing to advance the research agenda.
      Members of the National Hospice Work Group see strategic partnerships with
      academic entities as essential to the goal of advancing research in end-of-life
      care.

PMID- 17196911
TI  - Punctate midline myelotomy: a minimally invasive procedure for the treatment of
      pain in inextirpable abdominal and pelvic cancer.
AB  - The midline of the dorsal column contains a pathway that may be more important
      for transmitting visceral nociceptive signals than the spinothalamic tract.
      Punctate midline myelotomy, a neuroablative operation with the intent of
      interrupting the midline of the dorsal column, has demonstrated efficacy in the
      treatment of otherwise intractable abdominal and pelvic cancer pain. The
      indications, technical procedure, outcomes, and complications of all published
      clinical studies of punctate midline myelotomy are reviewed. The lesion level of
      the spinal cord and the depth of the incision are discussed, with the focus on
      the feasibility of this technique.

PMID- 17196917
TI  - The acceptability to older drivers of different types of licensing restriction.
AB  - The primary objective of this study was to determine the acceptability of various
      driving restrictions to older drivers. Licensed drivers aged 65 years or more
      living in the community in the Ottawa, Ontario area were recruited by means of
      posters and advertisements in regional and local newspapers. We recruited 86
      subjects, 56 men and 30 women with a mean age of 75 years (50 urban and 36 rural
      residents). The subjects completed a one-hour interview with one of two trained
      study nurses during which their driving restriction preferences (utilities) were
      determined using a modified standard gamble technique. Highly endorsed
      restrictions included regular assessment by the Ministry of Transportation (mean
      utility 0.94), driving with vehicle adaptations (0.94) and daytime driving only
      (0.93). Less acceptable restrictions included avoidance of roads with a speed
      limit greater than 60 km/h (0.50), limitation of destinations (0.45), driving
      only within a 10-km radius of home (0.45) and requirement of another licensed
      driver in the vehicle (0.42). Our subjects' preferences appeared to be inversely
      related to the impact on autonomy and the ability to access the community. These
      findings may be useful to motor transport administrators in designing effective
      restricted licensing programs that are acceptable to older drivers.

PMID- 17196918
TI  - Traffic signal phasing at intersections to improve safety for alcohol-affected
      pedestrians.
AB  - Alcohol-affected pedestrians are among the highest-risk groups involved in
      pedestrian casualty crashes. This paper investigates the opportunities to use a
      modified form of traffic signal operation during high-risk periods and at high
      risk locations to reduce alcohol-affected pedestrian crashes and the severity of
      injuries that might otherwise occur. The 'Dwell-on-Red' treatment involves
      displaying a red traffic signal to all vehicle directions during periods when no
      vehicular traffic is detected, so that drivers approach high-risk intersections
      at a lower speed than if a green signal were displayed. Vehicle speed data were
      collected before and after treatment activation at both a control and treatment
      site. Speed data were collected both 30 m prior to and at the intersection stop
      line. The treatment was associated with a reduction in mean vehicle speeds of 3.9
      kph (9%) and 11.0 kph (28%) at 30 m and stop line collection points,
      respectively, and substantial reductions in the proportion of vehicles travelling
      at threatening speeds with regard to the severity of pedestrian injury. Other
      important road safety concerns may also benefit from this form of traffic signal
      modification, and it is recommended that other areas of application be explored,
      including the other severe trauma categories typically concentrated around
      signalised intersections.

PMID- 17196919
TI  - Of gnomes and leprechauns: the recruitment of recent and categorical contexts in
      social judgment.
AB  - Participants rated schematic faces from two categories, gnomes and leprechauns,
      on feature widths and pleasantness of facial configuration. Three target faces
      shared critical facial features across categories while two contextual faces
      extended the range for that category to include either very wide or very narrow
      features. In Experiment 1a, results indicated contextual effects on judgments of
      target faces when they were rated in separate categorical blocks [Wedell, D. H.,
      & Pettibone, J. C. (1999). Preference and the contextual basis of ideals in
      judgment and choice. Journal of Experimental Psychology: General, 128, 346-361],
      but not when faces from both categories were rated together in Experiment 1b. Two
      additional experiments explored this failure to use categorical information.
      Categorical context was found to produce contrast effects on descriptive ratings
      of feature width when participants were forced to rely on name cues rather than
      actual faces in Experiment 2. In Experiment 3, both contrast effects on
      descriptive ratings and assimilation effects on ideals for pleasantness were
      found when the names for the faces were learned separately for each category.
      These results identify constraints on the nature of category-based stereotyping
      effects on judgment while isolating the influence of recent and categorical
      context.

PMID- 17196921
TI  - Comparative analysis of complex liquids based on a multi-experimental approach.
AB  - A parallel analysis is here presented between the results gathered by the author
      by means of three different experimental approaches--Dielectric analysis,
      Thermally Stimulated Depolarization (TSD) and Differential Scanning Calorimetry
      (DSC)--on some multi-component complex liquids consisting of association
      structures of self-assembling amphiphiles as, water-in-oil microemulsions. The
      highly dispersed nature of these systems was evidenced with the dielectric study:
      a Maxwell-Wagner relaxation was found to characterize this type of systems. The
      structural evolution of the system, against water addition, was well described by
      the orientational processes induced in the liquid samples by a nearly static
      electric field as in the TSD method. The investigation by DSC, besides offering a
      basic picture of the system's thermodynamics, allowed the measure of the specific
      heat, at constant pressure, at the higher order percolative phase transition. The
      comparison between the results obtained on samples processed with identical
      thermal cycles, once under the action of an impressed electric field as in TSD,
      and, once in the absence of any impressed electric field as in DSC, did help
      distinguish three main concentration intervals within which structurally
      different systems form namely, isotropic microemulsions and two liquid
      crystalline structures of lyotropic type.

PMID- 17196920
TI  - High serum nitric oxide levels in patients with severe leptospirosis.
AB  - Leptospirosis is a globally distributed zoonosis of major public health
      importance and is associated with severe disease manifestations such as acute
      renal failure and pulmonary haemorrhage syndrome. However, the extent to which
      the pathogenesis of leptospirosis mimics sepsis caused by Gram-negative bacteria
      remains unknown. The aim of this study was to evaluate serum levels of nitric
      oxide (NO) in patients diagnosed with severe leptospirosis. Sera from 35
      confirmed cases of severe leptospirosis and 13 healthy subjects were analysed.
      Patients with severe leptospirosis had significantly higher NO levels compared to
      healthy individuals (30.82+/-10.90 microM versus 3.86+/-1.34 microM, P < 0.001),
      indicating that this immune mediator plays a role in the underlying systemic
      inflammatory response.

PMID- 17196922
TI  - Determination of anandamide and other fatty acyl ethanolamides in human serum by
      electrospray tandem mass spectrometry.
AB  - We developed a new selective liquid chromatography-electrospray ionization-tandem
      mass spectrometry method for the identification and quantification of anandamide
      (AEA), an endogenous cannabinoid receptor ligand, and other bioactive fatty acid
      ethanolamides (FAEs) in biological samples. Detection limit (0.025 pmol for AEA
      and 0.1 pmol for palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)) and
      quantification limit (0.2 pmol for AEA and 0.4 pmol for OEA and PEA) were in the
      high fmol to low pmol range for all analytes. Linear correlations (r(2)=0.99)
      were observed in the calibration curves for standard AEA over the range of 0.025
      25 pmol and for standard PEA and OEA over the range of 0.1-500 pmol. This method
      provides a time-saving and sensitive alternative to existing methods for the
      analysis of FAEs in biological samples.

PMID- 17196923
TI  - A single nucleotide polymorphism genotyping method using phosphate-affinity
      polyacrylamide gel electrophoresis.
AB  - To date, various methods have been developed to facilitate the genotyping of a
      single nucleotide polymorphism (SNP) for aiding in the diagnosis and treatment of
      inherited diseases. The most commonly used method for SNP genotyping is an allele
      specific hybridization procedure using an expensive fluorochrome-labeled
      oligonucleotide probe and a specialized fluorescence analyzer. Here, we introduce
      a simple and reliable genotyping method using a 1:1 mixture of 5'-phosphate
      labeled and nonlabeled allele-specific polymerase chain reaction (PCR) primers.
      The method is based on the difference in mobility of the phosphorylated and
      nonphosphorylated PCR products (in the same number of basepairs) on phosphate
      affinity polyacrylamide gel electrophoresis. The phosphate-affinity site is a
      polyacrylamide-bound dinuclear zinc(II) complex, which preferentially captures
      the 5'-phosphate-labeled allele-specific product compared with the corresponding
      nonlabeled product. The obtained DNA migration bands can be visualized by
      ethidium bromide staining. We demonstrate the genotyping of a SNP reported in a
      human cardiac sodium channel gene, SCN5A, using this novel procedure.

PMID- 17196924
TI  - Two-component atomic force microscopy recognition imaging of complex samples.
AB  - Biological complexes are typically multisubunit in nature and the processes in
      which they participate often involve protein compositional changes in themselves
      and/or their target substrates. Being able to identify more than one type of
      protein in complex samples and to track compositional changes during processes
      would thus be very useful. Toward this goal, we describe here a single-molecule
      technique that can simultaneously identify two types of proteins in
      compositionally complex samples. It is an adaptation of the recently developed
      atomic force microscopy (AFM) recognition imaging technique but involves the
      tethering of two different types of antibodies to the AFM tip and sequential
      blocking with appropriate antigenic peptides to distinguish the recognition from
      each antibody. The approach is shown to be capable of simultaneously identifying
      in a single AFM image two specific components, BRG1 and beta-actin, of the human
      Swi-Snf ATP-dependent nucleosome remodeling complex and two types of histones,
      H2A and H3, in chromatin samples.

PMID- 17196925
TI  - Effects of slip testing parameters on measured coefficient of friction.
AB  - Slips and falls are a major cause of injuries in the workplace. Devices that
      measure coefficient of friction (COF) of the shoe-floor-contaminant interface are
      used to evaluate slip resistance in various environments. Testing conditions
      (e.g. loading rate, timing, normal force, speed, shoe angle) are believed to
      affect COF measurements; however, the nature of that relationship is not well
      understood. This study examines the effects of normal force (NF), speed, and shoe
      angle on COF within physiologically relevant ranges. A polyvinyl chloride shoe
      was tested using a modified industrial robot that could attain high vertical
      loads and relatively high speeds. Ground reaction forces were measured with a
      loadcell to compute COF. Experiment #1 measured COF over a range of NF (
      approximately 100-500 N) for two shoe angles (10 degrees and 20 degrees ), four
      speeds (0.05, 0.20, 0.35, and 0.50 m/s), and two contaminants (diluted detergent
      and diluted glycerol). Experiment #2 further explored speed effect by testing
      seven speeds (0.01, 0.05, 0.20, 0.35, 0.50, 0.75, and 1.00 m/s) at a given NF
      (350 N) and shoe angle (20 degrees ) using the same two contaminants. Experiment
      #1 showed that faster speeds significantly decreased COF, and that a complex
      interaction existed between NF and shoe angle. Experiment #2 showed that
      increasing speed decreased COF asymptotically. The results imply that COF is
      dependent on film thickness separating the shoe and the heel, which is dependent
      on speed, shoe angle, and NF, consistent with tribological theory.

PMID- 17196926
TI  - Adventure tourism and adventure sports injury: the New Zealand experience.
AB  - The primary aims of this study were to establish a client injury baseline for the
      New Zealand adventure tourism and adventure sport sector, and to examine patterns
      and trends in claims for injury during participation in adventure activities.
      Content analysis of narrative text data for compensated injuries occurring in a
      place for recreation and sport over a 12-month period produced over 15,000 cases
      involving adventure tourism and adventure sport. As found in previous studies in
      New Zealand, highest claim counts were observed for activities that are often
      undertaken independently, rather than commercially. Horse riding, tramping,
      surfing and mountain biking were found to have highest claim counts, while hang
      gliding/paragliding/parasailing and jet boating injuries had highest claim costs,
      suggesting greatest injury severity. Highest claim incidence was observed for
      horse riding, with female claimants over-represented for this activity. Younger
      male claimants comprised the largest proportion of adventure injuries, and falls
      were the most common injury mechanism.

PMID- 17196927
TI  - Carotenoids as protection against sarcopenia in older adults.
AB  - Sarcopenia, or loss of muscle mass and strength, plays a major role in the
      disablement process in older adults and increases the risk of impaired physical
      performance, falls, physical disability, frailty, and death. Oxidative stress is
      a major mechanism implicated in the pathogenesis of sarcopenia; aging muscle
      shows increased oxidative damage to DNA, protein, and lipids. Carotenoids quench
      free radicals, reduce damage from reactive oxygen species, and appear to modulate
      redox-sensitive transcription factors such as NF-kappaB that are involved in the
      upregulation of IL-6 and other proinflammatory cytokines. Recent epidemiological
      studies in community-dwelling older adults show that low serum/plasma carotenoids
      are independently associated with low skeletal muscle strength and the
      development of walking disability. These observations are consistent with a
      growing number of studies showing that a diet with high intake of fruits and
      vegetables is associated with a reduced risk of inflammation, hypertension,
      diabetes, cardiovascular disease, and mortality.

PMID- 17196928
TI  - Sphingomyelin-cholesterol and double stranded RNA relationship in the
      intranuclear complex.
AB  - The nuclear double-stranded RNA can be exported to the cytoplasm leading to the
      incorporation alternative aminoacids into the translated protein, can be retained
      to the nucleus playing a role on quality control nuclear function or can engaged
      by vigilin complex initiating the heterochromatin function. In the nucleus this
      RNA is associated to the protein, a small amount of DNA, sphingomyelin,
      phosphatidylcholine, and enzymes related to sphingomyelin metabolism such as
      sphingomyelinase and sphingomyelin-synthase constituting an intranuclear complex.
      Our data show an association between cholesterol and sphingomyelin that could
      play a role in double strand formation after RNA synthesis since [3H]-uridine
      incorporation demonstrates that nuclear double stranded RNA is new-synthesized.
      The presence of the lamin B as a protein of the intranuclear complex suggests
      that it could correspond to the transcription sites associated to the inner
      nuclear membrane.

PMID- 17196929
TI  - Escherichia coli as a platform for functional expression of plant P450 carotene
      hydroxylases.
AB  - Carotenoids and their derivatives are essential for growth, development, and
      signaling in plants and have an added benefit as nutraceuticals in food crops.
      Despite the importance of the biosynthetic pathway, there remain open questions
      regarding some of the later enzymes in the pathway. The CYP97 family of P450
      enzymes was predicted to function in carotene ring hydroxylation, to convert
      provitamin A carotenes to non-provitamin A xanthophylls. However, substrate
      specificity was difficult to investigate directly in plants, which mask enzyme
      activities by a complex and dynamic metabolic network. To characterize the
      enzymes more directly, we amplified cDNAs from a model crop, Oryza sativa, and
      used functional complementation in Escherichia coli to test activity and
      specificity of members of Clans A and C. This heterologous system will be
      valuable for further study of enzyme interactions and substrate utilization
      needed to understand better the role of CYP97 hydroxylases in plant carotenoid
      biosynthesis.

PMID- 17196930
TI  - Brain-specific transcript variants of 5' and 3' ends of mouse VPS13A and VPS13C.
AB  - Mutations in vacuolar protein sorting 13A (VPS13A) gene are responsible for
      chorea-acanthocytosis (ChAc). We previously determined the full-length sequence
      and exon-intron structure of mouse VPS13A and generated a ChAc model mouse by
      using the gene targeting technique. In the process, we found diverse 5' and 3'
      transcript variants. Since ChAc is a rare neurodegenerative disorder, the mouse
      model should be useful for investigation of ChAc molecular pathogenesis, and the
      model's brain specific variants of VPS13A will be indispensable in these
      investigations. In the present study, we investigated mouse VPS13A transcript
      variants. We found brain-specific variants of mouse VPS13A, which may be involved
      in the brain-specific pathology of ChAc. In addition, we identified for the first
      time mouse VPS13C cDNA sequences and brain-specific variants of VPS13C.

PMID- 17196931
TI  - Hsp90 inhibitors suppress HCV replication in replicon cells and humanized liver
      mice.
AB  - Persistent infection with hepatitis C virus (HCV) is a major cause of liver
      diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular
      carcinoma. Here we report that inhibition of heat shock protein 90 (Hsp90) is
      highly effective in suppressing HCV genome replication. In HCV replicon cells,
      HCV replication was reduced by Hsp90 inhibitors and by knockdown of endogenous
      Hsp90 expression mediated by small-interfering RNA (siRNA). The suppression of
      HCV replication by an Hsp90 inhibitor was prevented by transfection with Hsp90
      expression vector. We also tested the anti-HCV effect of Hsp90 inhibition in HCV
      infected chimeric mice with humanized liver. Combined administration of an Hsp90
      inhibitor and polyethylene glycol-conjugated interferon (PEG-IFN) was more
      effective in reducing HCV genome RNA levels in serum than was PEG-IFN
      monotherapy. These results suggest that inhibition of Hsp90 could provide a new
      therapeutic approach to HCV infection.

PMID- 17196932
TI  - Intracellular distribution of a speech/language disorder associated FOXP2 mutant.
AB  - Although a mutation (R553H) in the forkhead box (FOX)P2 gene is associated with
      speech/language disorder, little is known about the function of FOXP2 or its
      relevance to this disorder. In the present study, we identify the forkhead
      nuclear localization domains that contribute to the cellular distribution of
      FOXP2. Nuclear localization of FOXP2 depended on two distally separated nuclear
      localization signals in the forkhead domain. A truncated version of FOXP2 lacking
      the leu-zip, Zn2+ finger, and forkhead domains that was observed in another
      patient with speech abnormalities demonstrated an aggregated cytoplasmic
      localization. Furthermore, FOXP2 (R553H) mainly exhibited a cytoplasmic
      localization despite retaining interactions with nuclear transport proteins
      (importin alpha and beta). Interestingly, wild type FOXP2 promoted the transport
      of FOXP2 (R553H) into the nucleus. Mutant and wild type FOXP2 heterodimers in the
      nucleus or FOXP2 R553H in the cytoplasm may underlie the pathogenesis of the
      autosomal dominant speech/language disorder.

PMID- 17196933
TI  - Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human
      aortic endothelial cells: a possible involvement of androgen receptor.
AB  - Ginsenosides have been shown to stimulate nitric oxide (NO) production in aortic
      endothelial cells. However, the signaling pathways involved have not been well
      studied in human aortic endothelial cells. The present study was designed to
      examine whether purified ginsenoside Rb1, a major active component of ginseng
      could actually induce NO production and to clarify the signaling pathway in human
      aortic endothelial cells. NO production was rapidly increased by Rb1. The rapid
      increase in NO production was abrogated by treatment with nitric oxide synthetase
      inhibitor, L-NAME. Rb1 stimulated rapid phosphorylation of Akt (Ser473), ERK1/2
      (Thr202/Thr204) and eNOS (Ser1177). Rapid phosphorylation of eNOS (Ser1177) was
      prevented by SH-5, an Akt inhibitor or wortmannin, PI3-kinase inhibitor and
      partially attenuated by PD98059, an upstream inhibitor for ERK1/2. Interestingly,
      NO production and eNOS phosphorylation at Ser1177 by Rb1 were abolished by
      androgen receptor antagonist, nilutamide. The results suggest that PI3kinase/Akt
      and MEK/ERK pathways and androgen receptor are involved in the regulation of
      acute eNOS activation by Rb1 in human aortic endothelial cells.

PMID- 17196934
TI  - Mutations of acetylcholinesterase1 contribute to prothiofos-resistance in
      Plutella xylostella (L.).
AB  - Insensitive acetylcholinesterase (AChE) is involved in the resistance of
      organophosphorous and carbamate insecticides. We cloned a novel full-length AChE
      cDNA encoding ace1 gene from adult heads of the diamondback moth (DBM, Plutella
      xylostella). The ace1 gene encoding 679 amino acids has conserved motifs
      including catalytic triad, choline-binding site and acyl pocket. Northern blot
      analysis revealed that the ace1 gene was expressed much higher than the ace2 in
      all examined body parts. The biochemical properties of expressed AChEs showed
      substrate specificity for acetylthiocholine iodide and inhibitor specificity for
      BW284C51 and eserine. Three mutations of AChE1 (D229G, A298S, and G324A) were
      identified in the prothiofos-resistant strain, two of which (A298S and G324A)
      were expected to be involved in the prothiofos-resistance through three
      dimensional modeling. In vitro functional expression of AChEs in Sf9 cells
      revealed that only resistant AChE1 is less inhibited with paraoxon, suggesting
      that resistant AChE1 is responsible for prothiofos-resistance.

PMID- 17196935
TI  - Phospholipase Cgamma1 stimulates transcriptional activation of the matrix
      metalloproteinase-3 gene via the protein kinase C/Raf/ERK cascade.
AB  - The phospholipid hydrolase phospholipase Cgamma1 (PLCgamma1) plays a major role
      in regulation of cell proliferation, development, and cell motility.
      Overexpression of PLCgamma1 is associated with tumor development, and it is
      overexpressed in some tumors. Matrix metalloproteinase-3 (MMP-3) is a protein
      involved in tumor invasion and metastasis. Here, we demonstrate that
      overexpression of PLCgamma1 stimulates MMP-3 expression at the transcriptional
      level via the PKC-mediated Raf/MEK1/ERK signaling cascade. We propose that
      modulation of PLCgamma1 activity might be of value in controlling the activity of
      MMPs, which are important regulators of invasion and metastasis in malignant
      tumors.

PMID- 17196936
TI  - Brain-derived neurotrophic factor and risk of schizophrenia: an association study
      and meta-analysis.
AB  - Brain-derived neurotrophic factor (BDNF) is the most widely distributed
      neurotrophin in the central nervous system (CNS), and performs many biological
      functions such as neural survival, differentiation, and plasticity. Previous
      studies have suggested that variants in the BDNF gene increase the risk of
      schizophrenia. In this study, we genotyped one (GT)n dinucleotide repeat and
      three SNPs (rs6265, rs2030324, and rs2883187) in a Chinese sample (617 cases and
      672 controls). In addition, we performed an updated meta-analysis based on 16
      population-based case-control studies examining association between rs6265 and
      schizophrenia. In single-locus analysis, no significant association was found
      between BDNF polymorphisms and schizophrenia in our subjects. The meta-analysis
      based on Asian and Caucasian subjects did not give positive result that rs6265 is
      associated with schizophrenia. However, haplotype analysis found a common four
      locus haplotype is protective against schizophrenia (Case 3.1% vs Control 7%,
      p=0.0011). Our data provides evidence that BDNF is a susceptibility gene for
      schizophrenia in Chinese subjects.

PMID- 17196937
TI  - Characterization and role of Peptidase N from Salmonella enterica serovar
      Typhimurium.
AB  - ATP-independent peptidases are important during the distal steps of cytosolic
      protein degradation. The contribution of a member of this group, Peptidase N
      (PepN) was studied in Salmonella enterica serovar Typhimurium (Salmonella
      typhimurium). The DeltapepN strain displays greatly reduced cleavage of 9 out of
      a total of 13 exopeptidase substrates, demonstrating a significant contribution
      of PepN to cytosolic aminopeptidase activity. The cleavage profile of purified S.
      typhimurium PepN is Arg>Ala>Thr, demonstrating broad specificity. Comparative
      biochemical studies with purified PepN from Escherichia coli and S. typhimurium
      revealed the latter to be distinct: S. typhimurium PepN cleaves Thr-AMC more
      efficiently and is less sensitive to inhibition by N-ethylmaleimide. Studies with
      DeltapepN and PepN overexpression demonstrated its importance for growth during
      nutritional downshift in combination with high temperature stress. In summary, S.
      typhimurium PepN contributes significantly to cytosolic aminopeptidase activity
      and its role is manifested under selected stress conditions.

PMID- 17196938
TI  - Carbamylated erythropoietin protects the kidneys from ischemia-reperfusion injury
      without stimulating erythropoiesis.
AB  - Several studies have shown that erythropoietin (EPO) can protect the kidneys from
      ischemia-reperfusion injury and can raise the hemoglobin (Hb) concentration.
      Recently, the EPO molecule modified by carbamylation (CEPO) has been identified
      and was demonstrated to be able to protect several organs without increasing the
      Hb concentration. We hypothesized that treatment with CEPO would protect the
      kidneys from tubular apoptosis and inhibit subsequent tubulointerstitial injury
      without erythropoiesis. The therapeutic effect of CEPO was evaluated using a rat
      ischemia-reperfusion injury model. Saline-treated kidneys exhibited increased
      tubular apoptosis with interstitial expression of alpha-smooth muscle actin
      (alpha-SMA), while EPO treatment inhibited tubular apoptosis and alpha-SMA
      expression to some extent. On the other hand, CEPO-treated kidneys showed minimal
      tubular apoptosis with limited expression of alpha-SMA. Moreover, CEPO
      significantly promoted tubular epithelial cell proliferation without
      erythropoiesis. In conclusion, we identified a new therapeutic approach using
      CEPO to protect kidneys from ischemia-reperfusion injury.

PMID- 17196939
TI  - An intact homeobox domain is required for complete nuclear localization of human
      Nanog.
AB  - Nanog is a homeobox-containing transcriptional factor required for maintaining
      the pluripotent state of stem cells. We investigated the nuclear localization
      signal (NLS) motif required for human Nanog (hNanog) nuclear import. Mutation
      analysis revealed that a mutant containing only the homeodomain (HD) was
      exclusively localized to the nucleus, while other mutants containing either the N
      or C-terminal region (NR or CR) had impaired nuclear localization. In addition,
      NR and CR were exclusively localized to the nucleus when they were fused to the
      HD, indicating that complete nuclear localization is only driven by functional
      NLS motif(s) within the HD. Furthermore, partial loss of HD led to the incomplete
      localization of hNanog, suggesting that the intact HD is required for hNanog
      nuclear import. A series of deletion and site-directed mutagenesis within the HD
      revealed that two basic NLS motifs are located at the N-terminus and C-terminus
      of the HD and that both motifs are required for complete hNanog nuclear
      localization.

PMID- 17196940
TI  - The acetaminophen-derived bioactive N-acylphenolamine AM404 inhibits NFAT by
      targeting nuclear regulatory events.
AB  - AM404 is a synthetic TRPV1/CB(1) hybrid ligand with inhibitory activity on the
      anandamide transporter and is used for the pharmacological manipulation of the
      endocannabinoid system. It has been recently described that acetaminophen is
      metabolised in the brain to form the bioactive N-acylphenolamine AM404 and
      therefore, we have evaluated the effect of this metabolite in human T cells,
      discovering that AM404 is a potent inhibitor of TCR-mediated T-cell activation.
      Moreover, we found that AM404 specifically inhibited both IL-2 and TNF-alpha gene
      transcription and TNF-alpha synthesis in CD3/CD28-stimulated Jurkat T cells in a
      FAAH independent way. To further characterize the biochemical inhibitory
      mechanisms of AM404, we examined the signaling pathways that regulate the
      activation of the transcription factors NF-kappaB, NFAT and AP-1 in Jurkat cells.
      We found that AM404 inhibited both the binding to DNA and the transcriptional
      activity of endogenous NFAT and the transcriptional activity driven by the over
      expressed fusion protein Gal4-NFAT (1-415). However, AM404 did not affect early
      steps in NFAT signaling such as CD3-induced calcium mobilization and NFAT1
      dephosphorylation. The NFAT inhibitory activity of AM404 seems to be quite
      specific since this compound did not interfere with the signaling pathways
      leading to AP-1 or NF-kappaB activation. These findings provide new mechanistic
      insights into the immunological effects of AM404 which in part could explain some
      of the activities ascribed to the widely used acetaminophen.

PMID- 17196941
TI  - Protein kinases regulate glycine receptor binding in brain stem auditory nuclei
      after unilateral cochlear ablation.
AB  - Glycinergic synaptic inhibition is part of acoustic information processing in
      brain stem auditory pathways and contributes to the regulation of neuronal
      excitation. We found previously that unilateral cochlear ablation (UCA) in young
      adult guinea pigs decreased [3H]strychnine binding activity in several brain stem
      auditory nuclei. This study determined if the UCA-induced deficit could be
      regulated by protein kinase C (PKC), protein kinase A (PKA) or Ca2+/calmodulin
      dependent protein kinase II (CaMKII). The specific binding of [3H]strychnine was
      measured in slices of the dorsal (DCN), posteroventral (PVCN) and anteroventral
      (AVCN) cochlear nucleus (CN), the lateral (LSO) and medial (MSO) superior olive,
      and the inferior colliculus (IC) 145 days after UCA. Tissues from age-matched
      unlesioned animals served as controls. UCA induced deficits in specific binding
      in the AVCN, PVCN, and LSO on the ablated side and in the MSO bilaterally. These
      deficits were reversed by 3 microM phorbol 1,2-dibutyrate, a PKC activator, or
      0.2 mM dibutyryl-cAMP, a PKA activator. However, 50 nM Ro31-8220, a PKC
      inhibitor, and 2 microM H-89, a PKA inhibitor, had no effect in unlesioned
      controls and after UCA. In contrast, 4 microM KN-93, a CaMKII inhibitor, relieved
      or reversed the UCA-induced binding deficits and elevated binding in the IC.
      These findings suggest that a UCA-induced down-regulation of glycine receptor
      synthesis may have occurred via reduced phosphorylation of proteins that control
      receptor synthesis; this effect was reversed by diminishing CaMKII activity or
      increasing PKC and PKA activity.

PMID- 17196942
TI  - The ataxic groggy rat has a missense mutation in the P/Q-type voltage-gated Ca2+
      channel alpha1A subunit gene and exhibits absence seizures.
AB  - The groggy rat (strain name; GRY) exhibits ataxia, an unstable gait, and
      paroxysmal severe extension of the entire body. Adults show a reduction in size
      of the cerebellum and presynaptic and axon terminal abnormalities of Purkinje
      cells. These neurological abnormalities are inherited in an autosomal recessive
      manner, and the causative mutation has been named groggy (gry). In this study, we
      mapped gry on rat chromosome 19 and found a nonconservative missense (M251K)
      mutation in the alpha(1A) subunit of the P/Q-type voltage-gated Ca(2+) channel
      gene (Cacna1a) within the gry-critical region. This mutation was located at a
      highly conserved site close to the ion-selective pore and led to the shortening
      of the inactivation phase of the Ca(2+) channel current without a change of peak
      current density or current-voltage relationship in whole cell patch recordings of
      the recombinant Ca(2+) channel expressed in HEK cells. It has been well
      established that mice with a mutation at Cacna1a such as tottering and leaner
      show absence seizures. The Cacna1a-mutant GRY rat also exhibited absence-like
      seizures from 6 to 8 weeks of age, which were characterized by bilateral and
      synchronous 7-8 Hz spike-and-wave discharges concomitant with sudden immobility
      and staring, on cortical and hippocampal EEGs. The pharmacological profile of the
      seizures was similar to that of human absence epilepsy: the seizures were
      inhibited by ethosuximide and valproic acid but not phenytoin. Thus, the GRY rat
      with P/Q-type Ca(2+) channel disorders is a useful model for studying absence
      epilepsy and Cacna1a-related diseases.

PMID- 17196943
TI  - Event-related power modulations of brain activity preceding visually guided
      saccades.
AB  - To analyze the characteristics of the event-related desynchronization (ERD) and
      synchronization (ERS) of cortical rhythms during the preparation and execution of
      a lateralized eye movement, EEG was recorded in normal subjects during a visually
      guided task. Alpha and beta bands were investigated in three temporal intervals:
      a sensory period, a delay period and a saccade preparation period time locked
      with saccade onset. Modulations of ERD/ERS power, coupled with the task, reached
      the largest amplitudes over the frontal and parieto-occipital regions.
      Differences of oscillatory activity in the alpha bands revealed an intriguing
      pattern of asymmetry in parieto-occipital areas. Rightward saccades induced a
      larger desynchronization with respect to the leftward saccades in the left
      hemisphere, but not in the right. If representative, these findings are congruent
      to the established right-hemisphere dominance of the brain areas that direct
      attention. Moreover differences between the two alpha types emerged in the
      frontal areas before and during the saccade preparation periods, indicative of
      differential engagement of these areas depending on the task demands. In
      conclusion, the present approach shows that planning eye movements is linked with
      covert orienting of spatial attention and may supply a useful method for studying
      eye movements and selective attention-related processes.

PMID- 17196944
TI  - Lipid-lowering drugs in the MPTP mouse model of Parkinson's disease: fenofibrate
      has a neuroprotective effect, whereas bezafibrate and HMG-CoA reductase
      inhibitors do not.
AB  - We tested the ability of simvastatin, atorvastatin, fenofibrate and bezafibrate
      (two synthetic peroxisome proliferator-activated receptor-alpha (PPAR-alpha)
      agonists) to prevent dopaminergic cell death in the 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Tyrosine
      hydroxylase (TH) immunochemistry was performed 8 days after acute MPTP
      intoxication. When orally administered for the week prior to intoxication and a
      week thereafter, fenofibrate prevented the MPTP-induced dopaminergic cell loss in
      the substantia nigra pars compacta (SNpc) and attenuated the loss of tyrosine
      hydroxylase immunoreactivity in the striatum. The dosage of 1-methyl-4-phenyl
      pyridinium (MPP+) in the striatum by high-performance liquid chromatography
      indicated that fenofibrate did not affect MPTP metabolism. Bezafibrate had no
      effect and, strikingly, simvastatin and atorvastatin had a negative effect. We
      also demonstrated the presence of PPAR-alpha in the dopaminergic neurons of the
      murine substantia nigra. Our data suggest that PPAR-alpha activation by
      fenofibrate could have a neuroprotective effect in PD through inhibition of
      inflammation, oxidative stress and/or apoptosis.

PMID- 17196945
TI  - Platelet-activating factor contributes to the induction of long-term potentiation
      in the rat somatosensory cortex in vitro.
AB  - The contribution of platelet-activating factor (PAF) to the induction of
      neocortical LTP was examined in rat brain slices containing the primary
      somatosensory cortex (SI). Field potentials evoked by single pulse stimulation in
      cortical layer IV were recorded from layer II/III. In control experiments,
      tetanic high frequency stimulation (HFS) resulted in input-specific, NMDA
      receptor-dependent LTP (21.1+/-3.2%; mean+/-SEM; n=15; P<0.001). BN-52021 (5
      microM), an antagonist at the extracellular PAF receptor, weakened the HFS
      induced LTP to 12.4+/-2.7% (n=11; P<0.05). In contrast, HFS-induced LTP was
      significantly enhanced to 29.4+/-2.3% (n=11; P<0.05) when brain slices were
      superfused with ACSF containing the PAF receptor-agonist C-PAF (1.5 microM). The
      difference between LTP weakened by BN-52021 and LTP enhanced by C-PAF was highly
      significant (P<0.0005). These results suggest a physiological contribution of PAF
      to the induction of LTP in neocortical area SI. This contribution of PAF is
      mediated by an action at extracellular receptor sites.

PMID- 17196946
TI  - Thiamine deficiency during pregnancy leads to cerebellar neuronal death in rat
      offspring: role of voltage-dependent K+ channels.
AB  - Oxidative stress, selective neuronal loss, and diminished activity of thiamine
      dependent enzymes play a role in many neurodegenerative diseases, including
      Alzheimer's disease, Parkinson's disease and Huntington's disease. To further
      understand the major implications of thiamine deficiency (TD) in neuronal death,
      we induced TD during pregnancy and evaluated the effects on the offspring. The
      body and brain weights of pups from thiamine-deficient dams were significantly
      smaller than normal. Loss of neuronal viability was examined by trypan blue
      exclusion assay, and demonstrated increased cytotoxicity in primary cultures of
      TD neurons. Additionally, cerebellar cultures were exposed to thiamine-free cell
      culture medium to better explore the effects of thiamine withdrawal. Alterations
      in potassium current has previously been associated with the development of cell
      death. In this study, we examined the TD effects on delayed rectifier and A-type
      K+ channels, two well-known voltage-activated K+ channels involved in the
      regulation of action potential firing in cerebellar granule neurons. Current
      recordings were performed in cultured rat cerebellar granule neurons at day 7,
      using the whole-cell voltage-clamp technique. Our data demonstrate that thiamine
      deficiency provoked a significant decrease in the voltage-dependent K+ membrane
      conductance. Finally, TD markedly depressed the transient A-type K+ currents.

PMID- 17196947
TI  - Telomerase subunits expression variation between biopsy samples and cell lines
      derived from malignant glioma.
AB  - Although scientific advances have recognised the prognostic power of telomerase
      activity in different cancers, as yet there has been no investigation regarding
      the expression variation of telomerase subunits in glioma tissues and cell lines.
      In this study, a recurrent anaplastic ependymoma and seven glioblastoma biopsy
      samples, four cell lines and four controls including two normal brain tissues
      were analysed for telomerase subunit expression profiles together with telomerase
      activity. Since telomerase activity is linked to tumourgenesis, the genes were
      analysed with respect to their expression variation. TEP1 was expressed in all
      glioma cell lines and 70% of glioblastoma tissues, in addition to the control
      brain tissues. Tankyrase was expressed in 85% of the glioblastoma tissues and was
      down-regulated in the recurrent anaplastic ependymoma tissue control cell lines.
      However, it was expressed in the control tissues. Dyskerin was expressed in all
      cell lines and tissues apart from U87-MG and NHA cells and the recurrent
      anaplastic ependymoma tissue. As expected, PARP1 and GAPDH showed constitutive
      expression throughout all cell lines and tissues since both are known to be
      housekeeping genes. hTERT was expressed in all glioma cell lines and tissues but
      was absent in the control cells and tissues. Telomerase activity was absent in
      IPDDC-A2 cells and 57% of the glioblastoma tissues. These results suggest that
      hTERT expression and not telomerase activity possibly represents a simple and
      reliable biological diagnostic tool.

PMID- 17196948
TI  - Insulin expression in the brain and pituitary cells of tilapia (Oreochromis
      niloticus).
AB  - While the presence of immunoreactive insulin in the central nervous system of
      many vertebrate species is well known, the origin of brain insulin is still
      debated. In this study, we applied RT-PCR, quantitative RT-PCR (qRT-PCR), and
      Northern hybridization to examine expression of the insulin gene in different
      tissues of an adult teleost fish, the Nile Tilapia (Oreochromis niloticus). We
      found that the insulin gene is transcribed at a high level in Brockmann bodies
      (pancreatic islet organs) and at a low level in the brain and pituitary gland. In
      the brain, insulin transcripts were detected in all areas by qRT-PCR and in situ
      hybridization. The highest level of insulin mRNA was found in the hypothalamus.
      The level of insulin transcription in the pituitary gland was 6-fold higher than
      that in the brain and 4.6-fold higher than that in the hypothalamus. Furthermore,
      insulin mRNA and immunoreactive insulin-like protein was detected in the
      pituitary gland using in situ hybridization, immunohistochemistry, and Western
      blot analysis. Our results indicate that in adult tilapia insulin expression is
      not restricted to the endocrine pancreatic cells, but also occurs in endocrine
      cells of the pituitary gland and in the neuronal cells of the brain, suggesting
      that the brain/pituitary gland might represent extrapancreatic origin of insulin
      production.

PMID- 17196949
TI  - Role of substantia innominata in cerebral blood flow autoregulation.
AB  - Ascending projections from the substantia innominata (SI) may have an important
      role in the regulation of cerebral blood flow (CBF). However, several reports
      have suggested that unilateral lesion of the SI does not affect CBF
      autoregulation. On the other hand, it is also reported that several cortical and
      subcortical functions may be regulated not only by ipsilateral SI, but also by
      contralateral SI. Thus, the objective of this study is to test the hypothesis
      that bilateral lesions of the SI affect CBF autoregulation. Experiments were
      performed on anesthetized male Sprague-Dawley rats. Ibotenic acid or
      physiological saline was microinjected into bilateral SI. Rats were classified
      into four groups as follows: bilateral SI lesion rats (ibotenic acid was injected
      bilaterally), left or right SI lesion rats (ibotenic acid was injected into the
      unilateral SI and saline into the contralateral SI), and control rats (saline was
      injected bilaterally). Ten days after injection, CBF in the left frontal cortex
      was measured by laser-Doppler flowmetry during stepwise controlled hemorrhagic
      hypotension. In bilateral SI lesion rats, CBF was started to decrease
      significantly at 80 mm Hg (p<0.01). In the other three groups, CBF was well
      maintained until 50 mm Hg. Changes in CBF through stepwise hypotension in
      bilateral SI lesion rats were significantly different from the other groups
      (p<0.01). These results suggest that bilateral SI regulates cortical vasodilator
      mechanisms during hemorrhagic hypotension. Under unilateral SI lesion, some
      compensatory effects from the contralateral SI may maintain CBF autoregulation.

PMID- 17196950
TI  - Proteomic analysis of rat cortical neurons after fluoxetine treatment.
AB  - The known neurochemical effect of most currently available antidepressants is the
      enhancement of the synaptic levels of monoamine neurotransmitters. However, the
      existence of other mechanisms has been suggested to justify the significant delay
      between the modulation of the monoaminergic system and the clinical effects. In
      order to investigate the effects of the antidepressant fluoxetine (a prototypical
      serotonin selective re-uptake inhibitor) and to improve the understanding of its
      mechanism of action, we performed a proteomic investigation in rat primary
      cortical neurons exposed sub-chronically to this antidepressant. Cortical neurons
      were treated for 3 days with 1 microM fluoxetine or vehicle. Protein extracts
      were processed for 2D gel characterization. Image analysis allowed the
      identification of six proteins differently expressed by more than 100% and seven
      proteins differently expressed by more than 50% (P<0.05). Nine proteins were
      identified by mass spectrometry. Among them, cyclophilin A, 14-3-3 protein
      z/delta and GRP78 are involved in neuroprotection, in serotonin biosynthesis and
      in axonal transport, respectively. This study showed that the primary culture of
      cortical neurons is a suitable system for studying the effects of fluoxetine
      action and may contribute to improve the understanding of fluoxetine
      psychotherapeutic action and the mechanisms mediating the long-term effects of
      this antidepressant treatment.

PMID- 17196951
TI  - The role of complement in the adherence of microbubbles to dysfunctional arterial
      endothelium and atherosclerotic plaque.
AB  - OBJECTIVE: To determine whether serum complement C3 mediates adherence of albumin
      encapsulated microbubbles to vascular endothelium in the development of
      atherosclerotic plaques. METHODS: Adherence of microbubbles to aortic endothelium
      was examined with scanning electron microscopy following intravenous injection of
      20% intralipid in wild-type mice, genetic complement-deficient mice (C3-/-), and
      in pharmacologic C3-depleted wild-type mice. In a second experimental model,
      atherosclerostic plaque was induced in apolipoprotein E-deficient mice (apoE-/-),
      and adherence of microbubbles to atherosclerotic plaques was evaluated using
      fluorescent microscopy of fluorescein isothiocynate-conjugated microbubbles.
      Finally, imaging of aortas was performed in eight rats (four JCR:LA-cp
      atherosclerosis-prone rats on high cholesterol diets; four controls) following
      intravenous albumin microbubble injections (PESDA) to determine whether
      microbubble adherence to the endothelium could be detected with low mechanical
      index pulse sequence schemes. RESULTS: Scanning electron microscopy confirmed the
      adherence of microbubbles to the endothelial cells of the aorta in wild-type mice
      following induction of hypertriglyceridemia but not in C3-depleted mice.
      Microbubble adherence to the endothelial surface of atherosclerotic plaque was
      confirmed in all apoE-/- mice (median 172 microbubbles/field; compared to a
      median of 3 microbubbles/field in cobra venom factor-treated apoE-/- mice; p <
      0.001). Low mechanical index ultrasound imaging detected microbubble adherence in
      all JCR atherosclerosis prone rats even in the absence of vasomotor or
      phenotypical evidence of endothelial dysfunction. The numbers of adherent
      microbubbles correlated with serum triglyceride levels, and were seen in
      conjunction with increased endothelial nitric oxide synthase activity.
      CONCLUSIONS: Complement C3 binds to albumin-encapsulated microbubbles and
      mediates microbubble adherence to vascular endothelium both early and late in the
      atherosclerotic process.

PMID- 17196952
TI  - Nicotinic component of galantamine in the regulation of amyloid precursor protein
      processing.
AB  - Current therapies for Alzheimer's disease treatment rely mainly on
      acetylcholinesterase inhibitors, improving central cholinergic neurotransmission.
      Among these molecules, galantamine (GAL) has an interesting pharmacological
      profile as it is both a reversible acetylcholinesterase inhibitor and an
      allosteric potentiator of nicotinic cholinergic receptors. We investigated the
      effect of GAL on the metabolism of the amyloid precursor protein (APP) in
      differentiated SH-SY5Y neuroblastoma cells. The rationale was based on the
      suggestion that cholinergic activity may also be involved in the regulation of
      APP metabolism. We studied the acute effect on APP metabolism measuring the
      secretion of sAPPalpha in the conditioned medium of cells. Following 2h
      treatment, GAL 10microM promoted a strong increase in the release of sAPPalpha,
      the maximal effect approaching on average three-fold baseline value. The compound
      appeared to increase the release of sAPPalpha, with a mechanism dependent upon an
      indirect cholinergic stimulation. The effect of GAL was prevented by pre
      treatment with alpha-bungarotoxin (40nM) but not low (nanomolar) atropine
      concentrations, suggesting the specific involvement of nicotinic cholinergic
      receptors.

PMID- 17196953
TI  - Component volumes of unsaturated phosphatidylcholines in fluid bilayers: a
      densitometric study.
AB  - The specific volumes of six 1,2-diacylphosphatidylcholines with monounsaturated
      acyl chains (diCn:1PC, n=14-24 is the even number of acyl chain carbons) in fluid
      bilayers in multilamellar vesicles dispersed in H(2)O were determined by the
      vibrating tube densitometry as a function of temperature. From the data obtained
      with diCn:1PC (n=14-22) vesicles in combination with the densitometric data from
      Tristram-Nagle et al. [Tristram-Nagle, S., Petrache, H.I., Nagle, J.F., 1998.
      Structure and interactions of fully hydrated dioleoylphosphatidylcholine
      bilayers. Biophys. J. 75, 917-925.] and Koenig and Gawrisch [Koenig, B.W.,
      Gawrisch, K., 2005. Specific volumes of unsaturated phosphatidylcholines in the
      liquid crystalline lamellar phase. Biochim. Biophys. Acta 1715, 65-70.], the
      component volumes of phosphatidylcholines in fully hydrated fluid bilayers at 30
      degrees C were obtained. The volume of the acyl chain CH and CH(2) group is
      V(CH)=22.30 A(3) and V(CH2) =A(3), respectively. The volume of the headgroup
      including the glyceryl and acyl carbonyls, V(H), and the ratio of acyl chain
      methyl and methylene group volumes, r=V(CH3):V(CH2) are linearly interdependent:
      V(H)=a-br, where a=434.41 A(3) and b=-55.36 A(3) at 30 degrees C. From the
      temperature dependencies of component volumes, their isobaric thermal
      expansivities (alpha(X)=V(X)(-1)(partial differential V(X)/ partial differential
      T) where X=CH(2), CH, or H were calculated: alpha(CH2)=118.4x10(-5)K(-1),
      alpha(CH)=71.0x10(-5)K(-1), alpha(H)=7.9x10(-5)K(-1) (for r=2) and
      alpha(H)=9.6x10(-5)K(-1) (for r=1.9). The specific volume of diC24:1PC changes at
      the main gel-fluid phase transition temperature, t(m)=26.7 degrees C, by 0.0621
      ml/g, its specific volume is 0.9561 and 1.02634 ml/g at 20 and 30 degrees C,
      respectively, and its isobaric thermal expansivity alpha=68.7x10(-5) and
      109.2x10(-5)K(-1) below and above t(m), respectively. The component volumes and
      thermal expansivities obtained can be used for the interpretation of X-ray and
      neutron scattering and diffraction experiments and for the guiding and testing
      molecular dynamics simulations of phosphatidylcholine bilayers in the fluid
      state.

PMID- 17196954
TI  - Association of IL1B polymorphisms with gastric cancer in a Chinese population.
AB  - OBJECTIVES: To investigate the association between IL1B polymorphisms and risk of
      gastric cancer in a Chinese population, seven SNPs in the IL1B gene were selected
      for this study. METHODS: A multiplex genotyping method, which is based on adapter
      ligation and allele-specific amplification, was established to type seven SNPs on
      the IL1B gene simultaneously. One hundred and forty-one non-cancer outpatients
      and 97 patients with gastric cancer were genotyped, and the relation between IL1B
      polymorphisms and gastric cancer was statistically analyzed. RESULTS: The seven
      SNPs were successfully typed and the results were consistent with those obtained
      by both Sanger's sequencing and PCR-RFLP. Handling with statistical analysis, we
      observed significantly different genotype frequencies of 0794C>T (chi(2)=6.11,
      P=0.05), 1274C>T (chi(2)=6.86, P=0.03) and 2143T>C (chi(2)=6.86, P=0.03) between
      patients and controls. CONCLUSION: ALM-ASA is a potential method for multiplex
      SNP typing with a low consumption of genomic DNA. SNPs 0794C>T, 1274C>T, and
      2143T>C are associated with gastric cancer.

PMID- 17196956
TI  - Distinct distal regulatory elements control tyrosinase expression in melanocytes
      and the retinal pigment epithelium.
AB  - Pigment cells of mammals are characterized by two different developmental
      origins: cells of the retinal pigment epithelium (RPE) originate from the optic
      cup of the developing forebrain, whereas melanocytes arise from the neural crest.
      The pigmentation gene tyrosinase is expressed in all pigment cells but
      differentially regulated in melanocytes and RPE. The tyrosinase promoter does not
      confer strong expression in pigment cells in vivo, while inclusion of a distal
      regulatory element at position -15 kb is necessary and sufficient to provide
      strong expression in melanocytes. Nevertheless, the regulatory elements
      responsible for correct spatial and temporal tyrosinase expression in the RPE
      remained unidentified so far. In this report, we show that a 186 kb BAC
      containing the tyrosinase gene provides transgene expression in both RPE and
      melanocytes indicating the presence of regulatory sequences required for
      expression in the RPE. A deletion analysis of the BAC was performed demonstrating
      that a RPE-regulatory element resides between -17 and -75 kb. Using multi-species
      comparative genomic analysis we identified three conserved sequences within this
      region. When tested in transgenic mice one of these sequences located at -47 kb
      targeted expression to the RPE. In addition, deletion of this regulatory element
      within a tyrosinase::lacZ BAC provided evidence that this sequence is not only
      sufficient but also required for correct spatial and temporal expression in the
      RPE. The identification of this novel element demonstrates that tyrosinase gene
      expression is controlled by separate distal regulatory sequences in melanocytes
      and RPE.

PMID- 17196955
TI  - Asymmetric localizations of LIN-17/Fz and MIG-5/Dsh are involved in the
      asymmetric B cell division in C. elegans.
AB  - LIN-44/Wnt and LIN-17/Frizzled (Fz) function in a planar cell polarity (PCP)-like
      pathway to regulate the asymmetric B cell division in Caenorhabditis elegans. We
      observed asymmetric localization of LIN-17/Frizzled (Fz) and MIG-5/Dishevelled
      (Dsh) during the B cell division. LIN-17::GFP was asymmetrically localized within
      the B cell prior to and after the B cell division and correlated with B cell
      polarity. Asymmetric localization of LIN-17::GFP was dependent upon LIN-44/Wnt
      and MIG-5/Dsh function. The LIN-17 transmembrane domain and a portion of the
      cysteine-rich domain (CRD) were required for LIN-17 function and asymmetric
      distribution to the B cell daughters, while the conserved KTXXXW motif was only
      required for function. MIG-5::GFP was also asymmetrically localized within the B
      cell prior to and after the B cell division in a LIN-17- and LIN-44-dependent
      manner. Functions of the MIG-5 DEP, PDZ and DIX domains were also conserved.
      Thus, a novel PCP-like pathway, in which LIN-17 and MIG-5 are asymmetrically
      localized, is involved in the regulation of B cell polarity.

PMID- 17196957
TI  - Defects in eye development in transgenic mice overexpressing the heparan sulfate
      proteoglycan agrin.
AB  - The importance of heparan sulfate proteoglycans (HSPGs) in neurodevelopment is
      becoming increasingly clear. However, studies on HSPGs are hampered by
      pleiotropic effects when synthesis or modification of heparan sulfate itself is
      targeted, and by redundancy when the core proteins are altered. Gain-of-function
      experiments can sometimes circumvent these issues. Here we establish that
      transgenic mice overexpressing the HSPG agrin have severe ocular dysgenesis. The
      defects occur through a gain-of-function mechanism and penetrance is dependent on
      agrin dosage. The agrin-induced developmental defects are highly variable, and
      include anophthalmia, persistence of vitreous vessels, and fusion of anterior
      chamber structures. A frequently observed defect is an optic stalk coloboma
      leading to the misdifferentiation of the optic stalk as retina, which becomes
      continuous with the forebrain. The defects in optic-stalk differentiation
      correlate with reduced sonic hedgehog immunoreactivity and overexpansion of the
      PAX6 domain from the retina into the optic stalk. The ocular phenotypes
      associated with agrin overexpression are dependent on genetic background,
      occurring with high penetrance in inbred C57BL/6J mice. Distinct loci sensitizing
      C57BL/6J mice to agrin-induced dysgenesis were identified. These results indicate
      that agrin overexpression will provide a tool to explore the molecular
      interactions of the extracellular matrix and cell surface in eye development, and
      provide a means for identifying modifier loci that sensitize mice to
      developmental eye defects.

PMID- 17196958
TI  - Potentiation of cyclic AMP-mediated proopiomelanocortin gene promoter activity by
      calcium channel blockers in a pituitary cell line.
AB  - Although it is known that the expression of proopiomelanocortin, a precursor
      protein of adrenocorticotropic hormone, can be affected by a variety of drugs,
      the effects of calcium channel blockers have not been studied. This study
      examined the effect of calcium channel blockers on proopiomelanocortin gene
      expression. Mouse pituitary tumor cells stably transfected with approximately 0.7
      kb of the rat proopiomelanocortin 5' promoter-luciferase fusion gene were
      stimulated by potassium chloride, corticotropin-releasing hormone (CRH) or
      forskolin, in the presence or absence of calcium channel blockers (nifedipine,
      verapamil and diltiazem). Assessments were made of proopiomelanocortin gene
      promoter activity and cyclic adenosine 3',5'-monophosphate (cyclic AMP) efflux. A
      dose-dependent enhancement of CRH- or forskolin-stimulated proopiomelanocortin
      promoter activity was observed with nifedipine and verapamil, but not diltiazem.
      Cyclic AMP efflux induced by CRH or forskolin was also enhanced by nifedipine and
      verapamil. In the presence of isobutylmethylxanthine, a phosphodiesterase
      inhibitor, enhancement of proopiomelanocortin promoter activity and cyclic AMP
      efflux by nifedipine and verapamil was not observed. It was concluded that the
      inhibition of phosphodiesterase is a probable mechanism for the effect of
      nifedipine and verapamil on CRH or forskolin induction of proopiomelanocortin
      gene expression.

PMID- 17196959
TI  - Gas6/Axl-PI3K/Akt pathway plays a central role in the effect of statins on
      inorganic phosphate-induced calcification of vascular smooth muscle cells.
AB  - Apoptosis is essential for the initiation and progression of vascular
      calcification. Recently, we showed that 3-hydroxy-3-methylglutaryl (HMG) CoA
      reductase inhibitors (statins) have a protective effect against vascular smooth
      muscle cell calcification by inhibiting apoptosis, where growth arrest-specific
      gene 6 (Gas6) plays a pivotal role. In the present study, we clarified the
      downstream targets of Gas6-mediated survival signaling in inorganic phosphate
      (Pi)-induced apoptosis and examined the effect of statins. We found that
      fluvastatin and pravastatin significantly inhibited Pi-induced apoptosis and
      calcification in a concentration-dependent manner in human aortic smooth muscle
      cells (HASMC), as was found with atorvastatin previously. Gas6 and its receptor,
      Axl, expression were downregulated in the presence of Pi, and recombinant human
      Gas6 (rhGas6) significantly inhibited apoptosis and calcification in a
      concentration-dependent manner. During apoptosis, Pi suppressed Akt
      phosphorylation, which was reversed by rhGas6. Wortmannin, a specific
      phosphatidylinositol 3-OH kinase (PI3K) inhibitor, abolished the increase in Akt
      phosphorylation by rhGas6 and eliminated the inhibitory effect of rhGas6 on both
      Pi-induced apoptosis and calcification, suggesting that PI3K-Akt is a downstream
      signal of the Gas6-mediated survival pathway. Pi reduced phosphorylation of Bcl2
      and Bad, and activated caspase 3, all of which were reversed by rhGas6. The
      inhibitory effect of statins on Pi-induced apoptosis was accompanied by
      restoration of the Gas6-mediated survival signal pathway: upregulation of Gas6
      and Axl expression, increased phosphorylation of Akt and Bcl2, and inhibition of
      Bad and caspase 3 activation. These findings indicate that the Gas6-mediated
      survival pathway is the target of statins' effect to prevent vascular
      calcification.

PMID- 17196960
TI  - Enalapril improves impairment of SERCA-derived relaxation and enhancement of
      tyrosine nitration in diabetic rat aorta.
AB  - We investigated the involvement of angiotensin II and vascular smooth muscle
      sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) function in the impaired NO
      induced relaxation seen in established streptozotocin-induced diabetes. Plasma
      angiotensin II levels, which were elevated in untreated diabetic rats (vs age
      matched controls), were improved by treatment with the angiotensin-converting
      enzyme inhibitor enalapril. Systolic blood pressure was significantly decreased
      in chronic enalapril-treated diabetics (vs the other two groups). Intact aortae
      from diabetic rats and chronic angiotensin II-infused control rats, but not those
      from diabetic rats treated with enalapril, showed impaired endothelium-dependent
      relaxations to acetylcholine (vs controls). The relaxation induced by Angeli's
      Salt (a NO donor) was significantly impaired in endothelium-denuded aortae from
      diabetic rats (vs controls) but it was normalised by enalapril treatment. After
      preincubation with the irreversible SERCA inhibitor, thapsigargin, the relaxation
      induced by Angeli's Salt was significantly impaired in endothelium-denuded aortae
      from the controls, but not from the diabetics, and there was no significant
      difference between the thapsigargin-treated groups. Nitrotyrosine, an indirect
      marker of peroxynitrite, was markedly increased in aortic smooth muscle from
      diabetic rats, while chronic enalapril administration reduced this increase.
      These results suggest that in streptozotocin-induced diabetic rats, excessive
      angiotensin II production may lead to the generation of peroxynitrite and that
      this may in turn trigger a dysfunction of vascular smooth muscle SERCA. Enalapril
      improved the diabetes-related impairments.

PMID- 17196961
TI  - Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity
      for Rac1 and Cdc42 and regulates neurite outgrowth.
AB  - Small GTPases of the Rho family, Rho, Rac, and Cdc42, are critical regulators of
      the changes in the actin cytoskeleton. Rho GTPases are typically activated by Dbl
      homology (DH)-domain-containing guanine nucleotide exchange factors (GEFs).
      Recent genetic and biochemical studies revealed a new type of GEF for the Rho
      GTPases. This family is composed of 11 genes, designated as Dock1 to Dock11, and
      is structurally divided into four classes Dock-A, -B, -C, and -D. Dock-A and -B
      subfamilies are typically GEFs specific for Rac1, while the Dock-D subfamily is
      specific for Cdc42. Here we show that Dock6, a member of the Dock-C subfamily,
      exchanges GDP for GTP for Rac1 and Cdc42 in vitro and in vivo. Furthermore, we
      find that, in mouse N1E-115 neuroblastoma cells, expression of Dock6 is increased
      following differentiation. Transfection of the catalytic Dock Homology Region-2
      (DHR-2) domain of Dock6 promotes neurite outgrowth mediated by Rac1 and Cdc42.
      Conversely, knockdown of endogenous Dock6 by small interference RNA reduces
      activation of Rac1 and Cdc42 and neurite outgrowth. Taken together, these results
      suggest that Dock6 differs from all of the identified Dock180-related proteins,
      in that it is the GEF specific for both Rac1 and Cdc42 and may be one of
      physiological regulators of neurite outgrowth.

PMID- 17196962
TI  - EGF AND TGF-alpha motogenic activities are mediated by the EGF receptor via
      distinct matrix-dependent mechanisms.
AB  - EGF and TGF-alpha induce an equipotent stimulation of fibroblast migration and
      proliferation. In spite of their homologous structure and ligation by the same
      receptor (EGFR), we report that their respective motogenic activities are
      mediated by different signal transduction intermediates, with p70(S6K)
      participating in EGF signalling and phospholipase Cgamma in TGF-alpha signalling.
      We additionally demonstrate that EGF and TGF-alpha motogenic activities may be
      resolved into two stages: (a) cell "activation" by a transient exposure to either
      cytokine, and (b) the subsequent "manifestation" of an enhanced migratory
      phenotype in the absence of cytokine. The cell activation and manifestation
      stages for each cytokine are mediated by distinct matrix-dependent mechanisms:
      motogenetic activation by EGF requires the concomitant functionality of EGFR and
      the hyaluronan receptor CD44, whereas activation by TGF-alpha requires EGFR and
      integrin alphavbeta3. Manifestation of elevated migration no longer requires the
      continued presence of exogenous cytokine and functional EGFR but does require the
      above mentioned matrix receptors, as well as their respective ligands, i.e.,
      hyaluronan in the case of EGF, and vitronectin in the case of TGF-alpha. In
      contrast, the mitogenic activities of EGF and TGF-alpha are independent of CD44
      and alphavbeta3 functionality. These results demonstrate clear qualitative
      differences between EGF and TGF-alpha pathways and highlight the importance of
      the extracellular matrix in regulating cytokine bioactivity.

PMID- 17196963
TI  - Intracellular characterization of DDX39, a novel growth-associated RNA helicase.
AB  - DDX39 belongs to the DEAD box RNA helicase family and is overexpressed in human
      lung squamous cell carcinoma. In this study, in order to seek the biological
      relevance of DDX39, we conducted its intracellular characterization. When
      expressed in 293 cells, DDX39 undergoes heavy ubiquitylation and the stability of
      DDX39 is regulated via a ubiqutin-proteasome pathway. DDX39 tethers ALY, an
      essential mRNA export factor, in vivo, confirming the role of DDX39 in the RNA
      splicing/export process. Co-immunoprecipitation and mass spectrometry analyses
      detected CIP29, a recently discovered growth and cell cycle-related factor, as a
      main DDX39-interacting protein. CIP29 binds RNA on its own and enhances RNA
      unwinding activity of DDX39. Thus, CIP29 physically and functionally associates
      with DDX39, suggesting their cooperation in the RNA metabolism. Extension of the
      search for the protein-protein interactions encompassing DDX39 identified
      FUS/TLS, a nucleic acid binding protein participating in both transcription and
      splicing, as a CIP29-interacting protein. The connections comprising ALY, DDX39,
      CIP29 and FUS/TLS may be an integral part of transcription, splicing and RNA
      export. We simultaneously examined the properties of DDX39-S, a C-terminally
      truncated variant of DDX39 stemmed from alternative splicing, to understand its
      biological significance.

PMID- 17196964
TI  - Juvenile-onset loss of lipid-raft domains in attractin-deficient mice.
AB  - Mutations at the attractin (Atrn) locus in mice result in altered pigmentation on
      an agouti background, higher basal metabolic rate and juvenile-onset
      hypomyelination leading to neurodegeneration, while studies on human immune cells
      indicate a chemotaxis regulatory function. The underlying biochemical defect
      remains elusive. In this report we identify a role for attractin in plasma
      membrane maintenance. In attractin's absence there is a decline in plasma
      membrane glycolipid-enriched rafts from normal levels at 8 weeks to a complete
      absence by 24 weeks. The structural integrity of lipid rafts depends upon
      cholesterol and sphingomyelin, and can be identified by partitioning within of
      ganglioside GM(1). Despite a significant fall in cellular cholesterol with
      maturity, and a lesser fall in both membrane and total cellular GM(1), these
      parameters lag behind raft loss, and are normal when
      hypomyelination/neurodegeneration has already begun thus supporting consequence
      rather than cause. These findings can be recapitulated in Atrn-deficient cell
      lines propagated in vitro. Further, signal transduction through complex membrane
      receptor assemblies is not grossly disturbed despite the complete absence of
      lipid rafts. We find these results compatible with a role for attractin in plasma
      membrane maintenance and consistent with the proposal that the juvenile-onset
      hypomyelination and neurodegeneration represent a defect in attractin-mediated
      raft-dependent myelin biogenesis.

PMID- 17196965
TI  - Raman spectroscopic evidence for nuclear disulfide in isolated lenses of
      hyperbaric oxygen-treated guinea pigs.
AB  - Our laboratory treats guinea pigs with hyperbaric oxygen (HBO) as a model for
      investigating the formation of nuclear cataract. Previous analyses of lens
      supernatants using this model have shown an increase in disulfide (-SS-) and loss
      of sulfhydryl (-SH) in the lens nucleus of O(2)-treated animals. In this paper,
      we have used the non-invasive technique of Raman spectroscopy to confirm these
      findings in intact, freshly-excised lenses. Guinea pigs were treated 3 times per
      week with HBO for a total of 50 (4 months of treatment) or 85 (7 months of
      treatment) times to induce an increased level of lens nuclear light scattering.
      Intact lenses were analyzed by Raman spectroscopy using a 514.5 nm laser and
      collecting the scattered light in a 90 degrees geometry. The laser beam was
      focused either in the lens nucleus or equatorial cortex. Changes in the levels of
      -SS- (503 cm(-1)) and -SH (2577 cm(-1)) vibrations were measured. Raman spectra
      were analyzed by fitting Lorentzian profiles to the observed data in the -SS- and
      -SH regions. -SS- levels in the O(2)-treated nucleus were found to have increased
      by a factor of 2.1 (p=0.0001) and 2.5 (p=0.001) after 50 and 85 HBO treatments,
      respectively, compared to age-matched controls. Based on previous biochemical
      analyses, the -SS- increase was due mainly to the formation of protein disulfide
      (PSSP) with contribution also from protein/thiol mixed disulfides, but not from
      oxidized glutathione. -SH levels in the O(2)-treated nucleus decreased by 13%
      (p=0.007) and 35% (p=0.001) after 50 and 85 HBO treatments, respectively,
      compared to age-matched controls. No significant increase in -SS- or loss of -SH
      was observed in the lens cortex of the O(2)-treated guinea pigs. The Raman
      spectroscopy results rule out the possibility that artifactual production of -SS-
      and loss of -SH occurred during homogenization of lenses in previous studies. The
      data provide additional evidence to support a link between O(2), disulfide
      crosslinking of lens crystallins in the nucleus, and nuclear cataract.

PMID- 17196966
TI  - Beta-sitosterol and 17beta-estradiol alter gonadal steroidogenic acute regulatory
      protein (StAR) expression in goldfish, Carassius auratus.
AB  - Fish exposed to the phytosterol beta-sitosterol (beta-sit) have decreased
      circulating hormone and cholesterol concentrations, and decreased gonadal intra
      mitochondrial cholesterol pools. The current study examined the potential for
      beta-sit to alter abundance of the key cholesterol transport protein,
      steroidogenic acute regulatory (StAR) protein, which delivers cholesterol to the
      first and rate-limiting steroidogenic enzyme P450 side chain cleavage (P450(scc))
      inside the mitochondria. Plasma testosterone (T) and lipids (cholesterol,
      lipoproteins and triglycerides) were also measured. Goldfish were exposed to 200
      microg/g beta-sit (97% pure or as a 72.6% pure phytosterol mixture) and 10
      microg/g 17beta-estradiol (E(2); estrogenic control) by intra-peritoneal Silastic
      implants for 21-days or for five-months. Plasma T was significantly decreased in
      male fish exposed to the phytosterol mixture following the long-term exposure
      (p<0.001). There were no differences in total cholesterol concentrations among
      treatments in the short- or long-term exposure, but male fish in the long-term
      exposure had significantly lower HDL as compared to control fish (p<0.025) with a
      corresponding increase in LDL. StAR transcript levels were unchanged following
      the short-term exposure, but were reduced after five months in male beta-sit fish
      (p=0.05) and E(2)-treated female fish (p=0.05). This reduction in StAR transcript
      abundance in conjunction with decreased plasma T and altered plasma lipoprotein
      fractions demonstrates a non-estrogenic effect of beta-sit. This is the first
      study to show that beta-sit has the capacity to alter gonadal StAR transcript
      abundance, offering a mechanism by which beta-sit disrupts reproductive endocrine
      endpoints.

PMID- 17196967
TI  - Effect of bezafibrate therapy on atherosclerotic aortic plaques detected by MRI
      in dyslipidemic patients with hypertriglyceridemia.
AB  - Fibrates reduce triglycerides (TG) and increase HDL-cholesterol levels, but there
      was no report showing plaque regression by fibrates. Using MRI, we investigated
      the effects of bezafibrate on aortic plaques in 22 dyslipidemic patients. All
      patients were asked to receive 400mg bezafibrate, but 8 who declined to have
      bezafibrate became the control group. Changes in vessel wall area (VWA) and lumen
      area (LA) from baseline to 1-year were evaluated. Bezafibrate reduced TG (-55%)
      and increased HDL-cholesterol levels (+29%). Bezafibrate reduced HDL size and
      increased LDL size. In thoracic plaques, bezafibrate reduced VWA (-6%, P<0.001)
      with no LA change, but VWA slightly progressed without bezafibrate (+5%). In
      abdominal plaques, bezafibrate reduced VWA (-8%, P<0.001) with LA increase (+3%,
      P<0.02), but VWA progressed without bezafibrate (+6%). VWA changes in thoracic
      and abdominal plaques correlated with TG reduction and HDL-cholesterol increase.
      Notably, VWA change in only abdominal plaques correlated with HDL size reduction
      and LDL size increase. Thus, bezafibrate induced plaque regression in thoracic
      and abdominal aortas with marked TG reduction and HDL-cholesterol increase, but
      the processes of plaque regression and vascular remodeling may differ between
      thoracic and abdominal aortas. However, because our study was not a controlled,
      randomized trial, further study is needed.

PMID- 17196968
TI  - Tissue strain amplification at the osteocyte lacuna: a microstructural finite
      element analysis.
AB  - A parametric finite element model of an osteocyte lacuna was developed to predict
      the microstructural response of the lacuna to imposed macroscopic strains. The
      model is composed of an osteocyte lacuna, a region of perilacunar tissue,
      canaliculi, and the surrounding bone tissue. A total of 45 different simulations
      were modeled with varying canalicular diameters, perilacunar tissue material
      moduli, and perilacunar tissue thicknesses. Maximum strain increased with a
      decrease in perilacunar tissue modulus and decreased with an increase in
      perilacunar tissue modulus, regardless of the thickness of the perilacunar
      region. An increase in the predicted maximum strain was observed with an increase
      in canalicular diameter from 0.362 to 0.421 microm. In response to the
      macroscopic application of strain, canalicular diameters increased 0.8% to over
      1.0% depending on the perilacunar tissue modulus. Strain magnification factors of
      over 3 were predicted. However, varying the size of the perilacunar tissue region
      had no effect on the predicted perilacunar tissue strain. These results indicate
      that the application of average macroscopic strains similar to strain levels
      measured in vivo can result in significantly greater perilacunar tissue strains
      and canaliculi deformations. A decrease in the perilacunar tissue modulus
      amplifies the perilacunar tissue strain and canaliculi deformation while an
      increase in the local perilacunar tissue modulus attenuates this effect.

PMID- 17196969
TI  - Headspace-solid phase microextraction-gas chromatography as a tool to define an
      index that establishes the retention capacity of the wine polymeric fraction
      towards ethyl esters.
AB  - A headspace-solid phase microextraction followed by gas chromatographic analysis
      (HS-SPME-GC) was developed to be applied in the study of the interactions between
      the wine polymeric fraction and the ethyl esters: ethyl hexanoate, ethyl
      octanoate, and ethyl decanoate. Wine models (WM) were prepared with 10% (v/v)
      aqueous ethanol at pH 3.5 with distinct wine polymeric concentrations prepared
      from white wine of Vitis vinifera L. var. Fernao-Pires: 1.0 g L(-1) (PWM1), with
      a polymeric concentration approaching the real one in wine; 10.0 g L(-1) (PWM10);
      and 30.0 g L(-1) (PWM30), saturated with polymeric fraction. A reference wine
      model (RWM) was prepared without polymeric fraction. Each volatile compound (4.0
      mg L(-1)) was added separately to the RWM and to the WM with the three levels of
      polymeric material (PWM). From the retention index (RI) calculated for each
      compound using the formula: [RI = 1 - (C(RWM) - C(PWM))/C(RWM)], where C(RWM) is
      the concentration of the compound in the RWM and C(PWM) is the concentration of
      the compound in the given PWM, the retention capacity of each wine polymeric
      fraction towards the three esters was established. The higher retention indexes
      were observed for ethyl decanoate, the more hydrophobic compound, and for the PWM
      with higher concentration. Furthermore, this study also suggested that the
      retained compounds are dosed to the headspace, which may promote the perception
      of their aroma for a longer period of time.

PMID- 17196970
TI  - Analysis of estrogens in river sediments by liquid chromatography-electrospray
      ionisation mass spectrometry. Comparison of tandem mass spectrometry and time-of
      flight mass spectrometry.
AB  - A method has been developed and optimised for the determination of two natural
      estrogens, estrone (E1) and 17beta-estradiol (E2), and one synthetic estrogen,
      17alpha-ethynylestradiol (EE2), in river sediments at the sub-ng/g level. This
      procedure includes microwave-assisted solvent extraction (MASE), solid-phase
      extraction and high-performance liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) with electrospray ionisation. Using sediments spiked with the three
      estrogens at 10 ng/g wet weight, efficient extraction (>92%) of all the three
      analytes was achieved by MASE, and whole-procedure recoveries ranged from 82 to
      98%. Optimisation of the LC separation allowed for substantial reduction of
      ionisation suppression in the electrospray source to a final level of <18%
      suppression. Time-of-flight mass spectrometry (TOF-MS) and MS/MS were compared
      for the analysis of sediment extracts, with the latter technique proving to be
      the most selective. The method detection limits achieved by LC-MS/MS were 15, 30
      and 40 pg/g for E1, E2 and EE2, respectively, which were 13-fold lower than those
      obtained by LC-TOF-MS. Analysis of river sediments collected from the River Ouse,
      UK, showed the presence of the natural estrogens at sub-ng/g level. E1 levels
      ranged from 0.40 ng/g (dry weight) to 3.30 ng/g while E2 levels ranged from <0.03
      to 1.20 ng/g and EE2 was never detected (<0.04 ng/g).

PMID- 17196971
TI  - Principles, developments and applications of on-line coupling of extraction with
      chromatography.
AB  - On-line coupling of extraction and chromatographic separation allows the whole
      analysis to be performed in a closed system. On-line systems are particularly
      useful when the analytes are labile, the amount of sample is limited, or very
      high sensitivity is required. Many on-line systems have been developed both for
      liquid and for solid samples. This review discusses the different instruments
      that have been constructed and the factors that need to be considered in the
      coupling. Selected illustrative applications are described to illustrate the
      potential of the on-line systems.

PMID- 17196972
TI  - Ion-pair chromatographic separation of glycoprotein derived oligosaccharides as
      their 8-aminopyrene-1,3,6-trisulfonic acid derivatives.
AB  - A reversed-phase ion-pair gradient liquid chromatographic method has been
      developed for separation of 8-aminopyrene-1,3,6-trisulfonic acid (APTS) labeled
      oligosaccharides derived from some glycoproteins. This separation mode has high
      capability for structural recognition of oligosaccharide isomers, which are
      usually difficult to separate using commonly used partition chromatography. In
      addition, some glycoprotein-derived complex-type oligosaccharides that have
      linkage isomers in one lactosamine arm and neuraminic acids existing in fetuin,
      as well as differences in the numbers of lactosamine branches, are separable
      using this mode. The ion-pair mode is promising for simple analyses of
      glycoprotein-derived oligosaccharides that are labeled with APTS.

PMID- 17196973
TI  - Do readers with autism make bridging inferences from world knowledge?
AB  - Individuals with autism frequently show impairments in text reading
      comprehension. This often is attributed to poor ability to draw inferences during
      reading and to inadequate access to relevant knowledge. The current study tested
      this hypothesis by measuring the time taken to read the same question, relating
      to either physical or social world knowledge, when it was either relevant or
      irrelevant to the bridging inference evoked by a preceding two-sentence vignette.
      In the study, 16 normally developing adolescents and 16 adolescents with autism
      were matched on word reading accuracy, chronological age, and vocabulary but
      differed significantly in text comprehension. A strong priming effect was found,
      robust over participants and over items; participants read those questions that
      were relevant to the inference evoked by the vignette faster than they read those
      questions that were irrelevant, and no interaction with group membership or type
      of knowledge was found. This indicates that readers with autism, just like
      controls, were activating appropriate world knowledge primed by implicit
      inferences while reading the vignettes. Thus, the comprehension problems in these
      readers cannot be attributed to an inability to make implicit inferences or to
      draw on relevant world knowledge. Instead, we suggest that these problems must be
      sought at a higher level of text processing.

PMID- 17196974
TI  - The effect of diet quality on physiological and life-history traits in the
      harvestman Pachylus paessleri.
AB  - The balance between energy acquisition and expenditure is critical to the
      survival and reproductive success of animals. Here we investigate the long-term
      effects of diet quality on physiological and life-history flexibility in the
      harvestman, Pachylus paessleri. We used cow meal as a protein-rich diet and
      potatoes as a carbohydrate-rich diet in order to reproduce two extreme conditions
      regarding food quality in harvestmen natural habitat. As proxy variables of the
      energy expenditure process, we quantified standard metabolic rate (maintenance),
      changes in body mass (somatic condition), and fecundity (reproduction). We found
      that animals consuming the protein-rich diet were able to increase both their
      body condition and fecundity. However, the increment in these two life-history
      traits was correlated with higher maintenance costs. In contrast, the
      carbohydrate-rich diet did not provide enough specific nutrients for reproductive
      events, although it may have allowed animals to survive for a long time. Thus,
      according to the quality of the diet available in the environment, harvestman
      females can adopt different life-history strategies correlated with phenotypic
      adjustments at anatomical and physiological levels. In the Mediterranean region,
      spatial and temporal changes in food quality are typical, so greater phenotypic
      flexibility is expected to cope with this kind of environmental variation.

PMID- 17196975
TI  - Association of alphaB-crystallin, a small heat shock protein, with actin: role in
      modulating actin filament dynamics in vivo.
AB  - Disruption of cytoskeletal assembly is one of the early effects of any stress
      that can ultimately lead to cell death. Stabilization of cytoskeletal assembly,
      therefore, is a critical event that regulates cell survival under stress. alphaB
      crystallin, a small heat shock protein, has been shown to associate with
      cytoskeletal proteins under normal and stress conditions. Earlier reports suggest
      that alphaB-crystallin could prevent stress-induced aggregation of actin in
      vitro. However, the molecular mechanisms by which alphaB-crystallin stabilizes
      actin filaments in vivo are not known. Using the H9C2 rat cardiomyoblast cell
      line as a model system, we show that upon heat stress, alphaB-crystallin
      preferentially partitions from the soluble cytosolic fraction to the insoluble
      cytoskeletal protein-rich fraction. Confocal microscopic analysis shows that
      alphaB-crystallin associates with actin filaments during heat stress and the
      extent of association increases with time. Further, immunoprecipitation
      experiments show that alphaB-crystallin interacts directly with actin. Treatment
      of heat-stressed H9C2 cells with the actin depolymerzing agent, cytochalasin B,
      failed to disorganize actin. We show that this association of alphaB-crystallin
      with actin is dependent on its phosphorylation status, as treatment of cells with
      MAPK inhibitors SB202190 or PD98059 results in abrogation of this association.
      Our results indicate that alphaB-crystallin regulates actin filament dynamics in
      vivo and protects cells from stress-induced death. Further, our studies suggest
      that the association of alphaB-crystallin with actin helps maintenance of
      pinocytosis, a physiological function essential for survival of cells.

PMID- 17196976
TI  - Group II intron folding under near-physiological conditions: collapsing to the
      near-native state.
AB  - The folding of group II intron ribozymes has been studied extensively under
      optimal conditions for self-splicing in vitro (42 degrees C and high magnesium
      ion concentrations). In these cases, the ribozymes fold directly to the native
      state by an apparent two-state mechanism involving the formation of an obligate
      intermediate within intron domain 1. We have now characterized the folding
      pathway under near-physiological conditions. We observe that compaction of the
      RNA proceeds slowly to completion, even at low magnesium concentration (3 mM).
      Kinetic analysis shows that this compact species is a "near-native" intermediate
      state that is readily chased into the native state by the addition of high salt.
      Structural probing reveals that the near-native state represents a compact domain
      1 scaffold that is not yet docked with the catalytic domains (D3 and D5).
      Interestingly, native ribozyme reverts to the near-native state upon reduction in
      magnesium concentration. Therefore, while the intron can sustain the intermediate
      state under physiological conditions, the native structure is not maintained and
      is likely to require stabilization by protein cofactors in vivo.

PMID- 17196977
TI  - Function blocking antibodies to neuropilin-1 generated from a designed human
      synthetic antibody phage library.
AB  - Non-immune (naive) antibody phage libraries have become an important source of
      human antibodies. The synthetic phage antibody library described here utilizes a
      single human framework with a template containing human consensus complementarity
      determining regions (CDRs). Diversity of the libraries was introduced at select
      CDR positions using tailored degenerate and trinucleotide codons that mimic
      natural human antibodies. Neuropilin-1 (NRP1), a cell-surface receptor for both
      vascular endothelial growth factor (VEGF) and class 3 semaphorins, is expressed
      on endothelial cells and neurons. NRP1 is required for vascular development and
      is expressed widely in the developing vasculature. To investigate the possibility
      of function blocking antibodies to NRP1 as potential therapeutics, and study the
      consequence of targeting NRP1 in murine tumor models, panels of antibodies that
      cross-react with human and murine NRP1 were generated from a designed antibody
      phage library. Antibody (YW64.3) binds to the CUB domains (a1a2) of NRP1 and
      completely blocks Sema3A induced neuron collapse; antibody (YW107.4.87) binds to
      the coagulation factor V/VIII domains (b1b2) of NRP1 and blocks VEGF binding and
      VEGF induced cell migration. YW107.4.87 inhibits tumor growth in animal xenograft
      models. These antibodies have provided valuable tools to study the roles of NRP1
      in vascular and tumor biology.

PMID- 17196978
TI  - High-resolution structural and thermodynamic analysis of extreme stabilization of
      human procarboxypeptidase by computational protein design.
AB  - Recent efforts to design de novo or redesign the sequence and structure of
      proteins using computational techniques have met with significant success. Most,
      if not all, of these computational methodologies attempt to model atomic-level
      interactions, and hence high-resolution structural characterization of the
      designed proteins is critical for evaluating the atomic-level accuracy of the
      underlying design force-fields. We previously used our computational protein
      design protocol RosettaDesign to completely redesign the sequence of the
      activation domain of human procarboxypeptidase A2. With 68% of the wild-type
      sequence changed, the designed protein, AYEdesign, is over 10 kcal/mol more
      stable than the wild-type protein. Here, we describe the high-resolution crystal
      structure and solution NMR structure of AYEdesign, which show that the
      experimentally determined backbone and side-chains conformations are effectively
      superimposable with the computational model at atomic resolution. To isolate the
      origins of the remarkable stabilization, we have designed and characterized a new
      series of procarboxypeptidase mutants that gain significant thermodynamic
      stability with a minimal number of mutations; one mutant gains more than 5
      kcal/mol of stability over the wild-type protein with only four amino acid
      changes. We explore the relationship between force-field smoothing and
      conformational sampling by comparing the experimentally determined free energies
      of the overall design and these focused subsets of mutations to those predicted
      using modified force-fields, and both fixed and flexible backbone sampling
      protocols.

PMID- 17196979
TI  - Reversible inhibition of Escherichia coli inorganic pyrophosphatase by fluoride:
      trapped catalytic intermediates in cryo-crystallographic studies.
AB  - Here, we describe high-resolution X-ray structures of Escherichia coli inorganic
      pyrophosphatase (E-PPase) complexed with the substrate, magnesium, or manganese
      pyrophosphate. The structures correspond to steps in the catalytic synthesis of
      enzyme-bound pyrophosphate (PP(i)) in the presence of fluoride as an inhibitor of
      hydrolysis. The catalytic reaction intermediates were trapped applying a new
      method that we developed for initiating hydrolytic activity in the E-PPase
      crystal. X-ray structures were obtained for three consecutive states of the
      enzyme in the course of hydrolysis. Comparative analysis of these structures
      showed that the Mn2+-supported hydrolysis of the phosphoanhydride bond is
      followed by a fast release of the leaving phosphate from the P1 site. The
      electrophilic phosphate P2 is trapped in the "down" conformation. Its movement
      into the "up" position most likely represents the rate-limiting step of Mn2+
      supported hydrolysis. We further determined the crystal structure of the Arg43Gln
      mutant variant of E-PPase complexed with one phosphate and four Mn ions.

PMID- 17196980
TI  - Flexibility and variability of TIMP binding: X-ray structure of the complex
      between collagenase-3/MMP-13 and TIMP-2.
AB  - The excessive activity of matrix metalloproteinases (MMPs) contributes to
      pathological processes such as arthritis, tumor growth and metastasis if not
      balanced by the tissue inhibitors of metalloproteinases (TIMPs). In arthritis,
      the destruction of fibrillar (type II) collagen is one of the hallmarks, with MMP
      1 (collagenase-1) and MMP-13 (collagenase-3) being identified as key players in
      arthritic cartilage. MMP-13, furthermore, has been found in highly metastatic
      tumors. We have solved the 2.0 A crystal structure of the complex between the
      catalytic domain of human MMP-13 (cdMMP-13) and bovine TIMP-2. The overall
      structure resembles our previously determined MT1-MMP/TIMP-2 complex, in that the
      wedge-shaped TIMP-2 inserts with its edge into the entire MMP-13 active site
      cleft. However, the inhibitor is, according to a relative rotation of
      approximately 20 degrees, oriented differently relative to the proteinase. Upon
      TIMP binding, the catalytic zinc, the zinc-ligating side chains, the enclosing
      MMP loop and the S1' wall-forming segment move significantly and in concert
      relative to the rest of the cognate MMP, and the active site cleft constricts
      slightly, probably allowing a more favourable interaction between the Cys1(TIMP)
      alpha-amino group of the inhibitor and the catalytic zinc ion of the enzyme.
      Thus, this structure supports the view that the central N-terminal TIMP segment
      essentially defines the relative positioning of the TIMP, while the flanking edge
      loops determine the relative orientation, depending on the individual target MMP.

PMID- 17196981
TI  - Three dimensional structure and implications for the catalytic mechanism of 6
      phosphogluconolactonase from Trypanosoma brucei.
AB  - Enzymes from the pentose phosphate pathway (PPP) are potential drug targets for
      the development of new drugs against Trypanosoma brucei, the causative agent of
      African sleeping disease: for instance, the 6-phosphogluconate dehydrogenase is
      currently studied actively for such purposes. Structural and functional studies
      are necessary to better characterize the associated enzymes and compare them to
      their human homologues, in order to undertake structure-based drug design studies
      on such targets. In this context, the crystal structure of 6
      phosphogluconolactonase (6PGL) from T. brucei, the second enzyme from PPP, was
      determined at 2.1 Angstroms resolution. Comparison of its sequence and structure
      to other related proteins in the 6PGL family with a known structure (Thermotoga
      maritima Tm6GPL 1PBT and Vibrio cholerae Vc6PGL (1Y89), which have not been
      discussed in print), or in the glucosamine-6-phosphate-deaminase family
      (hexameric Escherichia coli 1DEA and monomeric Bacillus subtilis 2BKV), allowed
      the identification of the 6PGL active site. In addition to the analysis of the
      crystal structure, 3D NMR interaction studies and docking experiments are
      reported here. Key residues involved in substrate binding or in catalysis were
      identified.

PMID- 17196983
TI  - Linkage between the intramembrane H-bond network around aspartic acid 83 and the
      cytosolic environment of helix 8 in photoactivated rhodopsin.
AB  - Understanding the coupling between conformational changes in the intramembrane
      domain and at the membrane-exposed surface of the bovine photoreceptor rhodopsin,
      a prototypical G protein-coupled receptor (GPCR), is crucial for the elucidation
      of molecular mechanisms in GPCR activation. Here, we have combined Fourier
      transform infrared (FTIR) and fluorescence spectroscopy to address the coupling
      between conformational changes in the intramembrane region around the retinal and
      the environment of helix 8, a putative cytosolic surface switch region in class-I
      GPCRs. Using FTIR/fluorescence cross-correlation we show specifically that
      surface alterations monitored by emission changes of fluorescein bound to Cys316
      in helix 8 of rhodopsin are highly correlated with (i) H-bonding to Asp83
      proximal of the retinal Schiff base but not to Glu122 close to the beta-ionone
      and (ii) with a metarhodopsin II (MII)-specific 1643 cm(-1) IR absorption change,
      indicative of a partial loss of secondary structure in helix 8 upon MII
      formation. These correlations are disrupted by limited C-terminal proteolysis but
      are maintained upon binding of a transducin alpha-subunit (G(talpha))-derived
      peptide, which stabilizes the MII state. Our results suggest that additional C
      terminal cytosolic loop contacts monitored by an amide II absorption at 1557 cm(
      1) play a functionally crucial role in keeping helix 8 in the position in which
      its environment is strongly coupled to the retinal-binding site near the Schiff
      base. In the intramembrane region, this coupling is mediated by the H-bonding
      network that connects Asp83 to the NPxxY(x)F motif preceding helix 8.

PMID- 17196982
TI  - Electron paramagnetic resonance study of structural changes in the O
      photointermediate of bacteriorhodopsin.
AB  - The structural changes of bacteriorhodopsin during its photochemical cycle, as
      revealed by crystal structures of trapped intermediates, have provided insights
      to the proton translocation mechanism. Because accumulation of the last
      photointermediate, O, appears to be hindered by lattice forces in the crystals,
      the only information about the structure of this state is from suggested
      analogies with the determined structures of the non-illuminated D85S mutant and
      wild-type bacteriorhodopsin at low pH. We used electron paramagnetic resonance
      spectroscopy of site-directed spin labels at the extracellular protein surface in
      membranes to test these models. Spin-spin dipolar interactions in the authentic O
      state compared to the non-illuminated state revealed that the distance between
      helices C and F increases by ca 4 Angstroms, there is no distance change between
      helices D and F, and the distance between helix D and helix B of the adjacent
      monomer increases. Further, the mobility changes of single labels indicate that
      helices E and F move outward from the proton channel at the center of the
      protein, and helix D tilts inward. The overall pattern of movements suggests that
      the model at acid pH is a better representation of the O state than D85S.
      However, the mobility analysis of spin-labels on the B-C interhelical loop
      indicates that the antiparallel beta-sheet maintains its ordered secondary
      structure in O, instead of the predicted disorder in the two structural models.
      During decay of the O state, the last step of the photocycle, a proton is
      transferred from Asp85 to proton release complex in the extracellular proton
      channel. The structural changes in O suggest the need of large conformational
      changes to drive the Arg82 side-chain back to its initial orientation towards
      Asp85, and to rearrange the numerous water molecules in this region in order to
      conduct the proton away from Asp85.

PMID- 17196984
TI  - Crystal structures reveal an induced-fit binding of a substrate-like Aza-peptide
      epoxide to SARS coronavirus main peptidase.
AB  - The SARS coronavirus main peptidase (SARS-CoV M(pro)) plays an essential role in
      the life-cycle of the virus and is a primary target for the development of anti
      SARS agents. Here, we report the crystal structure of M(pro) at a resolution of
      1.82 Angstroms, in space group P2(1) at pH 6.0. In contrast to the previously
      reported structure of M(pro) in the same space group at the same pH, the active
      sites and the S1 specificity pockets of both protomers in the structure of M(pro)
      reported here are in the catalytically competent conformation, suggesting their
      conformational flexibility. We report two crystal structures of M(pro) having an
      additional Ala at the N terminus of each protomer (M(+A(-1))(pro)), both at a
      resolution of 2.00 Angstroms, in space group P4(3)2(1)2: one unbound and one
      bound by a substrate-like aza-peptide epoxide (APE). In the unbound form, the
      active sites and the S1 specificity pockets of both protomers of M(+A(-1))(pro)
      are observed in a collapsed (catalytically incompetent) conformation; whereas
      they are in an open (catalytically competent) conformation in the APE-bound form.
      The observed conformational flexibility of the active sites and the S1
      specificity pockets suggests that these parts of M(pro) exist in dynamic
      equilibrium. The structural data further suggest that the binding of APE to
      M(pro) follows an induced-fit model. The substrate likely also binds in an
      induced-fit manner in a process that may help drive the catalytic cycle.

PMID- 17196985
TI  - Zebrafish Mib and Mib2 are mutual E3 ubiquitin ligases with common and specific
      delta substrates.
AB  - It was already known that both mind bomb (mib) and mind bomb-2 (mib2) encode E3
      ubiquitin ligases that target Delta in Notch activation. Here we further
      demonstrated that zebrafish Mib and Mib2, similar to their mouse orthologs, have
      a C-terminal-most RING finger-dependent E3 ubiquitin ligase activity. Mib and
      Mib2 are reciprocal E3 ubiquitin ligases and substrates. They function similarly
      in Notch signaling by using DeltaC as a common substrate. However, Mib2 behaves
      differently from Mib in DeltaD internalization. In addition, Mib and Mib2 bind
      differently to extracellular and intracellular parts of DeltaA and DeltaC.
      Finally, mutant Mibs, Mib(ta52b) with a missense mutation in the C-terminal-most
      RING finger (M1013R) and Mib(m132) with a premature stop codon that leads to a
      deletion of three RING fingers (C785stop), act dominant-negatively and compete
      with Mib2 in DeltaC ubiquitylation and internalization, suggesting a molecular
      basis for the antimorphic phenotypes (stronger than the null phenotypes) observed
      in zebrafish mib(ta52b) and mib(m132) alleles.

PMID- 17196986
TI  - Surgery-derived reactive oxygen species produced by polymorphonuclear leukocytes
      promote tumor recurrence: studies in an in vitro model.
AB  - Tissue injury induces the acute phase response, aimed at minimizing damage and
      starting the healing process. Polymorphonuclear leukocytes (PMNs) respond to the
      presence of specific chemoattractants and begin to appear in large numbers. The
      aim of this study was to investigate the influence of reactive oxygen species
      (ROS) produced by PMNs on the interaction between colon carcinoma cells and
      mesothelial cells. An experimental human in vitro model was designed using Caco-2
      colon carcinoma cells and primary cultures of mesothelial cells. Tumor cell
      adhesion to a mesothelial monolayer was assessed after preincubation of the
      mesothelium with stimulated PMNs and unstimulated PMNs. Mesothelial cells were
      also incubated with xanthine/xanthine oxidase (X/XO) complex producing ROS after
      which adhesion of Caco-2 cells was investigated and the expression of adhesion
      molecules (ICAM-1, VCAM-1, and CD44) by means of enzyme immunoassay. In the
      control situation the average adhesion of Caco-2 cells to the mesothelial
      monolayers was 23%. Mesothelial monolayers incubated with unstimulated PMNs
      showed a 25% increase of tumor cell adhesion (P < 0.05). The adhesion of tumor to
      the monolayers incubated with the N-formyl-methionyl-leucyl-phenylalanine
      stimulated PMNs increased with 40% (P < 0.01). Incubation of the mesothelium with
      X/XO resulted in an enhancement of adhesion of Caco-2 cells of 70% and an up
      regulation of expression of ICAM-1, VCAM-1, and CD44. This study reveals an
      increase of tumor cell adhesion to the mesothelium induced by incubating the
      mesothelial monolayers with PMNs. PMNs are producing a number of products, like
      proteolytic enzymes, cytokines, and ROS. These factors up-regulate the expression
      of adhesion molecules and in that way stimulate the adhesion of tumor to the
      mesothelium.

PMID- 17196987
TI  - From the combat medic to the forward surgical team: the Madigan model for
      improving trauma readiness of brigade combat teams fighting the Global War on
      Terror.
AB  - BACKGROUND: Medics assigned to combat units have a notable paucity of trauma
      experience. Our goal was to provide intense trauma refresher training for the
      conventional combat medic to better prepare them for combat casualty care in the
      War on Terror. MATERIALS AND METHODS: Our Tactical Combat Casualty Care Course
      (TC3) consisted of the following five phases: (1) One and one-half-day didactic
      session; (2) Half-day simulation portion with interactive human surgical
      simulators for anatomical correlation of procedures and team building; (3) Half
      day of case presentations and triage scenarios from Iraq/Afghanistan and
      associated skills stations; (4) Half-day live tissue lab where procedures were
      performed on live anesthetized animals in a controlled environment; and (5) One
      day field phase where live anesthetized animals and surgical simulators were
      combined in a real-time, field-training event to simulate realistic combat
      injuries, evacuation problems, and mass casualty scenarios. Data collection
      consisted of surveys, pre- and posttests, and after-action comments. RESULTS: A
      total of 1317 personnel participated in TC3 from October 2003 through May 2005.
      Over the overlapping study period from December 2004 to April 2005, 327 soldiers
      participated in the formal five-phase course. Three hundred four (94%) students
      were combat medics who were preparing for combat operations in Iraq or
      Afghanistan. Of those completing the training, 97% indicated their confidence and
      ability to treat combat casualties were markedly improved. Moreover, of those 140
      medics who took the course and deployed to Iraq for 1 year, 99% indicated that
      the principles taught in the TC3 course helped with battlefield management of
      injured casualties during their deployment. CONCLUSION: The hybrid training model
      is an effective method for training medical personnel to deal with modern battle
      injuries. This course increases the knowledge and confidence of combat medics
      deploying and fighting the Global War on Terrorism.

PMID- 17196989
TI  - Equal oncologic results for laparoscopic and open resection of adrenal
      metastases.
AB  - BACKGROUND: While open adrenalectomy is often performed for malignant adrenal
      tumors, increasing numbers of surgeons have adopted the laparoscopic approach.
      The postoperative benefits of laparoscopic adrenalectomy are well established,
      but questions persist about long-term oncologic outcomes when used for malignant
      lesions. The current study was undertaken to compare laparoscopic with open
      adrenalectomy for isolated adrenal metastases. METHODS: From March 1993 to April
      2006, 20 adults underwent adrenalectomy for isolated metastases to the adrenal
      gland. Three patients were excluded because of a concomitant nephrectomy (2) and
      an unresectable tumor (1). Patient demographics, tumor characteristics, and
      oncologic outcomes of the remaining patients were reviewed and analyzed. RESULTS:
      Of the 17 patients who received adrenalectomy for an isolated metastasis, there
      were 11 men and 6 women with a mean age of 58 +/- 3 y. Nine patients underwent
      laparoscopic adrenalectomy, and 8 patients had open adrenalectomy. Laparoscopic
      adrenalectomy was associated with less blood loss (63 +/- 8 mL versus 2207 +/-
      1067 mL, P=0.05), a lower complication rate (0% versus 63%, P=0.009), and a
      shorter length of stay (2.4 +/- 0.6 d versus 5.4 +/- 0.7 d, P=0.02). With a
      follow-up of up to 97 mo, there were no port site metastases, no tumor
      recurrences, and no difference in survival between laparoscopic and open
      adrenalectomy (median 19 months versus 17 months, 5-year survival 34% versus 54%,
      P=0.96). CONCLUSIONS: When not limited by tumor size or invasion of surrounding
      tissue, laparoscopic adrenalectomy is a safe alternative to open adrenalectomy
      with equivalent oncologic outcomes and clear postoperative benefit for patients
      with isolated metastases to the adrenal gland.

PMID- 17196988
TI  - Differential regulation of the superoxide dismutase family in experimental aortic
      aneurysms and rat aortic explants.
AB  - OBJECTIVE: Oxidative stress has been implicated in abdominal aortic aneurysm
      pathogenesis. This study sought to characterize the relevance of superoxide
      dismutases (SOD), a family of reactive oxygen catalyzing metalloenzymes,
      including manganese SOD (MnSOD), copper-zinc SOD (CuZnSOD), and extracellular SOD
      (EcSOD), in a rodent aortic aneurysm model. METHODS: Male rat infrarenal
      abdominal aortas were perfused with either saline (control) or porcine pancreatic
      elastase (6 U/mL). Aortic diameter was measured and aortas harvested on post
      operation days 1, 2, and 7 (N=5-6 per treatment group per day). MnSOD, CuZnSOD,
      EcSOD, catalase, MMP-2, MMP-9, and beta-actin expression in aortic tissue was
      determined by quantitative real-time PCR. MnSOD protein levels were measured
      using western immunoblotting and immunohistochemistry. In subsequent experiments,
      aimed at understanding the mechanism by which SOD is involved in AAA
      pathogenesis, rat aortic explants (RAEs) were incubated in media for 24 h in the
      presence of interleukin-1beta (IL-1beta, 2 ng/mL) and TEMPOL (SOD mimetic),
      catalase, or a combined SOD and catalase mimetic. Media MMP-2 and MMP-9 activity
      was determined by zymography. Data were analyzed by Student's t-tests and ANOVA.
      RESULTS: Elastase-perfused aortic diameters were significantly increased compared
      to control aortas by post-perfusion day 7 (P=0.016). MnSOD mRNA levels in
      elastase perfused aortas were 6.0 (P=0.05) and 7.5 times (P<0.01) greater than
      control aortas at post-perfusion days 1 and 2, respectively. EcSOD, CuZnSOD,
      catalase, and MMP-2 mRNA expression did not statistically vary between the two
      groups. MMP-9 expression was 3.5-fold higher in the elastase group on post
      perfusion day 2 (P=0.04). Western immunoblotting confirmed MnSOD protein was up
      regulated on day 4 in the elastase-perfused group compared to controls (P=0.02).
      Immunohistrochemistry demonstrated increased MnSOD staining in the elastase group
      on day 4. In RAE experiments, TEMPOL increased both MMP-9 and MMP-2 activity 2
      (P=0.09) and 3-fold (P=0.05), respectively, whereas catalase and the combined
      SOD/catalase mimetic failed to increase MMP-2 or MMP-9 activity. CONCLUSION:
      Experimental abdominal aortic aneurysm formation is associated with early
      increases in MnSOD expression and an increase in MMP-9 activity. Strategies aimed
      at inhibiting oxidative stress during AAA formation should focus on MnSOD.

PMID- 17196990
TI  - Quality of life outcomes in 599 cancer and non-cancer patients with colostomies.
AB  - BACKGROUND: A colostomy is known to impact negatively on a patient's quality of
      life (QOL). Concerns include incontinence, rectal discharge, gas, difficulties in
      returning to work, decreased sexual activity, and travel and leisure challenges.
      Reports have described QOL outcomes in cancer patients with colostomies and
      inflammatory bowel syndrome with colostomies, but little has been written
      regarding a comparison of cancer and non-cancer populations. The purpose of this
      study was to describe QOL issues of colostomy patients and compare these issues
      in cancer and non-cancer participants. MATERIALS AND METHODS: A QOL-ostomy
      questionnaire was mailed to 2455 California members of the United Ostomy
      Association. RESULTS: Of the 1457 respondents (59%), 599 had a colostomy. Most
      were results from cancer (517/599), with colorectal cancer being the most common
      diagnosis. The most common benign diagnoses were inflammatory bowel disease and
      diverticulitis. Demographics were similar, except for more females in the non
      cancer group (76%), and increased length of time with colostomy from the cancer
      group (mean 135.9 versus 106.4 months, P = 0.03). Common QOL problems included
      sexual problems, gas, constipation, travel difficulties, and dissatisfaction with
      appearance. Overall, cancer patients had less difficulty adjusting to their
      colostomies. CONCLUSIONS: Results confirmed the negative impact of a colostomy on
      QOL. While patients with cancer had a better overall QOL than those with benign
      processes, concerns were common to all colostomy patients. These results provide
      health care practitioners with information useful in discussing QOL concerns
      during pre-operation treatment decisions and post operative teaching and follow
      up care.

PMID- 17196992
TI  - An autopsy case with adult onset type II citrullinemia showing myelopathy.
AB  - Hepatic myelopathy is a rare neurological complication in patients with chronic
      liver failure and most patients who suffered from this disorder were demonstrated
      to have portal-systemic shunt. A 31-year-old man who was diagnosed as having
      adult-onset type II citrullinemia (CTLN2) and had a six-year history of recurrent
      hepatic encephalopathy showed progressive spastic paraparesis with no involvement
      of sensation and sphincter function. Examinations of cerebrospinal fluid and
      spinal MRI were normal. He suddenly died of acute exacerbation of hepatic
      encephalopathy with severe brain edema. The pathology of the spinal cord
      disclosed a localized degeneration of both lateral columns, the lesion being more
      remarkable in the lower segments of the cord. These clinical and pathological
      findings of hepatic myelopathy have not been noted in the many patients with
      CTLN2 previously reported, and our patient is unique in developing hepatic
      myelopathy without porto-caval shunting. Thus, repeated attacks of encephalopathy
      with hyperammonemia might secondarily have induced the myelopathy in this
      patient.

PMID- 17196991
TI  - Inhaled carbon monoxide prevents graft-induced intimal hyperplasia in swine.
AB  - BACKGROUND: Arteriovenous grafts often fail due to stenosis caused by venous
      anastomotic intimal hyperplasia (IH) and vascular smooth muscle cell (VSMC)
      proliferation. We examined the effects of inhaled carbon monoxide (CO), a product
      of heme-oxygenase-1 degradation of heme, on IH in a porcine arteriovenous graft
      model. MATERIALS AND METHODS: Eighteen Yorkshire pigs were divided into three
      groups (N = 6/group): (1) CO 100 ppm preoperatively for 1 h; (2) CO 250 ppm
      preoperatively for 1 h and intraoperatively; and (3) air-treated controls.
      Animals underwent end-to-side placement of polytetrafluoroethylene grafts
      connecting the common femoral artery and vein in both groins. Intimal thickness
      of the venous anastomosis at 30 days was measured blinded. The effect of CO on
      pig VSMC proliferation was studied in cell culture using [(3)H]thymidine
      incorporation. RESULTS: Pigs in the group receiving CO 250 ppm showed
      significantly less IH compared to animals in the group receiving 100 ppm and the
      air-treated group (267.5 +/- 21.4, 824 +/- 145.8, and 914.8 +/- 133.7 pixels,
      respectively, P < 0.0001). This effect was not observed when comparing the 100
      ppm group to the air-treated group. COHb levels were significantly elevated in
      the 100 ppm and 250 ppm compared to air-treated pigs (5.8 +/- 0.47, 13.2 +/- 1.0
      versus 2.3 +/- 0.11%, respectively, P < 0.001). Oxygen saturation, respiratory
      rate, and hemodynamics were not significantly different between the groups. CO
      induced VSMC growth arrest compared to air in vitro (11.9 +/- 4 versus 20.3 +/- 5
      10(3) counts/min/well, P < 0.01). CONCLUSION: A single exposure to a low
      concentration of inhaled CO (250 ppm) confers protection against intimal
      proliferation of VSMCs when given perioperatively in a clinically relevant model
      of arteriovenous grafts. These data are the first to suggest, in a clinically
      relevant model, the potential role for CO in clinical applications.

PMID- 17196993
TI  - Analytic formulas for discrete stochastic models of cell populations with both
      differentiation and de-differentiation.
AB  - Cell differentiation often appears to be a stochastic process particularly in the
      hemopoietic system. One of the earliest stochastic models for the growth of stem
      cell populations was proposed by Till et al. in 1964. In this model there are
      just two cell types: stem cells and specialized cells. At each time step there is
      a fixed probability that a stem cell differentiates into a specialized cell and a
      fixed probability that it undergoes mitosis to produce two stem cells. Even
      though this model is conceptually simple the myriad of possible outcomes has made
      it difficult to analyse. We present original closed-form expressions for the
      probability functions and a fast algorithm for computing them. Renewed interest
      in stem cells has raised questions about the effect de-differentiation has on
      stem cell populations. We have extended the stochastic model to include de
      differentiation and show that even a small amount of de-differentiation can have
      a large effect on stem cell population growth.

PMID- 17196994
TI  - Biomonitoring coastal seas - celebrating the contributions of our first North
      American editor - Dr. John (Jack) B. Pearce.

PMID- 17196996
TI  - Gaboxadol, a selective extrasynaptic GABA(A) agonist, does not generalise to
      other sleep-enhancing drugs: a rat drug discrimination study.
AB  - Gaboxadol is a selective extrasynaptic GABA(A) receptor agonist (SEGA) which
      enhances slow-wave sleep, and may act principally at extrasynaptic
      GABA(A)alpha4betadelta receptors. Drug discrimination is a very useful approach
      for exploring in vivo pharmacological similarities and differences between
      compounds and was therefore used to compare gaboxadol and zolpidem, an
      established hypnotic drug, against zopiclone, S-zopiclone, indiplon and
      tiagabine, all of which have been reported to enhance sleep. Gaboxadol
      generalised to itself, but not to zolpidem, zopiclone, S-zopiclone, R-zopiclone,
      indiplon or tiagabine. By contrast, zolpidem generalised to itself, zopiclone, S
      zopiclone and indiplon, but not to R-zopiclone (the inactive enantiomer of
      zopiclone), gaboxadol or tiagabine. This suggests that zolpidem, zopiclone, S
      zopiclone and indiplon share a discriminative stimulus, which may be mediated by
      their efficacy at GABA(A)alpha1betagamma receptors. Gaboxadol and tiagabine each
      have a different discriminative stimulus from all the other drugs tested.

PMID- 17196995
TI  - aCGH local copy number aberrations associated with overall copy number genomic
      instability in colorectal cancer: coordinate involvement of the regions including
      BCR and ABL.
AB  - In order to identify small regions of the genome whose specific copy number
      alteration is associated with high genomic instability in the form of overall
      genome-wide copy number aberrations, we have analyzed array-based comparative
      genomic hybridization (aCGH) data from 33 sporadic colorectal carcinomas. Copy
      number changes of a small number of specific regions were significantly
      correlated with elevated overall amplifications and deletions scattered
      throughout the entire genome. One significant region at 9q34 includes the c-ABL
      gene. Another region spanning 22q11-q13 includes the breakpoint cluster region
      (BCR) of the Philadelphia chromosome. Coordinate 22q11-q13 alterations were
      observed in 9 of 11 tumors with the 9q34 alteration. Additional regions on 1q and
      14q were associated with overall genome-wide copy number changes, while copy
      number aberrations on chromosome 7p, 7q, and 13q21.1-q31.3 were found associated
      with this instability only in tumors from patients with a smoking history. Our
      analysis demonstrates there are a small number of regions of the genome where
      gain or loss is commonly associated with a tumor's overall level of copy number
      aberrations. Our finding BCR and ABL located within two of the instability
      associated regions, and the involvement of these two regions occurring
      coordinately, suggests a system akin to the BCR-ABL translocation of CML may be
      involved in genomic instability in about one-third of human colorectal
      carcinomas.

PMID- 17196997
TI  - Qualitatively different memory impairments across frontal lobe subgroups.
AB  - Recall impairments in patients with lesions to the prefrontal cortex (PFC) have
      variously been attributed to problems with organisation at encoding, organisation
      at retrieval and monitoring at retrieval. Neuroimaging and recent theoretical
      work has associated the left lateral PFC with organisation and strategy
      production at encoding, and the right lateral PFC with organisation, error
      detection and monitoring at retrieval. However few lesion studies have been
      anatomically specific enough to test the direct predictions made by this work.
      Proactive interference, response to prompting, monitoring and organisational
      strategies were examined in 34 patients with frontal lobe lesions and 50 healthy
      controls using a structured verbal recall task, and the fractionation of deficits
      according to specific frontal lesion site was explored. Recall impairments were
      observed in the Right Lateral and Medial frontal subgroups. The Medial recall
      impairment was unaffected by manipulations at encoding or retrieval and was
      attributed to a "pure" memory deficit arising from disruption of the limbo
      thalamic system. The Right Lateral recall impairment was ameliorated by the
      provision of prompts at retrieval, indicating a strategic retrieval deficit. This
      intervention also resulted in an unusual pattern of intrusions, namely an
      increase in proactive interference responses compared with extra-list intrusions.
      However contrary to predictions no monitoring impairment was found. We offer two
      explanations for the pattern of performance in the Right Lateral group: failure
      of a right lateralised error detection and checking system, or an impairment in
      the active uncued initiation of a supervisory operation.

PMID- 17196998
TI  - Impaired sadness recognition is linked to social interaction deficit in autism.
AB  - Can autistic individuals use motion cues to identify simple emotions from 2D
      abstract animations? We compared emotion recognition ability using a novel test
      involving computerised animations, and a more conventional emotion recognition
      test using facial expressions. Adults with autism and normal controls, matched
      for age and verbal IQ, participated in two experiments. First, participants
      viewed a series of short (5s) animations. These featured an 'emotional' triangle,
      interacting with a circle. They were designed to evoke an attribution of emotion
      to the triangle, which was rated both in terms of anger, happiness, sadness or
      fear from its pattern of movement, and how animate ("living") it appeared to be.
      Second, emotion recognition was tested from standardised photographs of facial
      expressions. In both experiments, adults with autism were significantly impaired
      relative to comparisons in their perception of sadness. This is the first
      demonstration that, in autism, individuals can have difficulties both in the
      interpretation of facial expressions and in the recognition of equivalent
      emotions based on the movement of abstract stimuli. Poor performance in the
      animations task was significantly correlated with the degree of impairment in
      reciprocal social interaction, assessed by the Autism Diagnostic Observation
      Schedule. Our findings point to a deficit in emotion recognition in autism,
      extending beyond the recognition of facial expressions, which is associated with
      a functional impairment in social interaction skills. Our results are discussed
      in the context of the results of neuroimaging studies that have used animated
      stimuli and images of faces.

PMID- 17196999
TI  - Social housing conditions around puberty determine later changes in plasma
      cortisol levels and behavior.
AB  - A recent study found that male guinea pigs raised in large, mixed age/sex groups
      exhibited an unexpected suppression of their cortisol response at 4 mo of age.
      The present study examined the effect of social experience around the time of
      puberty on cortisol response suppression and social behavior at 4 mo of age.
      Males reared in large, mixed age/sex groups were either pair-housed with a female
      or moved to another large colony at 55 days of age. When tested at 4 mo, pair
      housed males exhibited much higher levels of courtship and sexual behavior than
      did colony-housed males, and a shorter latency to begin courtship when with an
      unfamiliar adult female. In addition, pair-housed males showed much higher levels
      of agonistic behavior and a shorter latency to escalated aggression with an
      unfamiliar adult male. Pair-housed males also had lower basal cortisol
      concentrations and exhibited a greater increment in cortisol levels when isolated
      in a novel cage than did colony-housed males. Finally, pair-housed males showed a
      smaller increment in cortisol levels when with the stimulus female or male than
      when isolated, but colony-housed males did not. The findings demonstrate that
      social housing conditions around the time of puberty can have pervasive effects
      on social behavior and hypothalamic-pituitary-adrenal (HPA) activity in 4-mo-old
      males. Further, these findings are consistent with the notion that changes in HPA
      activity contribute to social behavior development beyond the time of sexual
      maturity.

PMID- 17197000
TI  - Thermoregulatory changes around the time of sleep onset.
AB  - A causal relationship between declining nocturnal core temperature, increasing
      peripheral temperature, and sleep onset has been reported. The exact trigger for
      these thermoregulatory changes around sleep onset, however, is unknown. Our aim
      was to examine one possible trigger: prior knowledge of bedtime. Fourteen young,
      healthy male subjects (mean age+/-sem: 21.9+/-0.6 years), participated in a
      randomized, single-blind crossover study, where knowledge of bedtime was
      manipulated. Following a baseline night, subjects completed three experimental
      nights: (A) aware of bedtime; (B) no knowledge of bedtime; (C) misinformed about
      bedtime. In all conditions lights were turned off at each subject's habitual
      bedtime (determined from sleep diaries), to individually standardize the time of
      lights off. Polysomnography, rectal and peripheral (foot) temperatures were
      recorded continuously on each night. There was no significant difference in the
      time of sleep onset among conditions (mean+/-s.d.: 11:55 h+/-0.73 min), and in
      all conditions sleep onset occurred at the same rectal temperature. A significant
      difference in the temperature gradient between rectal and peripheral temperatures
      among the conditions was evident from 90 min to 40 min prior to sleep onset
      (P=0.05), with subjects achieving a more rapid rate of temperature change in the
      B and C condition relative to condition A. The present findings suggest that
      knowledge of bedtime may modulate changes in temperature around the time of sleep
      onset. It appears that there is an optimal core body temperature at which to
      initiate sleep, and changes in the rate of peripheral heat loss may assist in
      achieving this optimal temperature, and hence facilitate sleep onset.

PMID- 17197001
TI  - Changes in plasma metabolites and muscle glycogen are correlated to bovine
      spongiform encephalopathy in infected dairy cattle.
AB  - During the clinical phase of bovine spongiform encephalopathy (BSE), a
      significant decrease was observed in the ratio of muscle glycogen to plasma L
      lactic acid concentrations in BSE infected field case and experimentally infected
      dairy cattle compared with healthy control cattle (P<0.001), this being due to
      changes in the concentration of both metabolites in the BSE infected cattle
      compared with the control group. Furthermore, the concentration of plasma alanine
      was significantly increased (P<0.05) in the infected animals. No significant
      difference was detected between these two groups in the ratio of hepatic glycogen
      to plasma lactate. We infer that BSE infected cattle exhibit signs of altered
      energy metabolism and when applied in conjunction with changes in other
      metabolite biomarkers these changes may be useful for discriminating BSE infected
      cattle from healthy cattle or those suffering with other disorders or diseases.

PMID- 17197002
TI  - Annual rhythmicity and maturation of physiological parameters in goats.
AB  - This study was conducted to investigate seasonal rhythmicity and maturation of
      physiological parameters in goats. Five kids (Capra hircus, Maltese breed) were
      studied for 24 months, starting at 5 months of age. Rectal temperature and
      various blood-borne substances (melatonin, cholesterol, urea, total bilirubin,
      albumin, glucose, calcium, magnesium, phosphate, and sodium) were measured once a
      month at dawn and dusk. Serum bilirubin concentration exhibited statistically
      significant 12-month rhythmicity, and melatonin concentration exhibited 6-month
      rhythmicity. Changes in the dusk-to-dawn difference in rectal temperature during
      the course of the study provided suggestive evidence that the circadian rhythm of
      body temperature in goats is not fully developed until the end of the second year
      of life. The results documented also maturational changes in cholesterol
      production and blood glucose regulation.

PMID- 17197003
TI  - Infectious canine hepatitis: an "old" disease reemerging in Italy.
AB  - Four outbreaks of infectious canine hepatitis (ICH) occurring in Italy between
      2001 and 2006 are reported. Three outbreaks were observed in animal shelters of
      southern Italy, whereas a fourth outbreak involved two purebred pups imported
      from Hungary few days before the onset of clinical symptoms. In all outbreaks
      canine adenovirus type 1 (CAV-1) was identified by virus isolation and PCR. In
      three outbreaks, other canine viral pathogens were detected, including canine
      distemper virus, canine parvovirus or canine coronavirus. The present study shows
      that CAV-1 is currently circulating in the Italian dog population and that
      vaccination is still required.

PMID- 17197004
TI  - Experimental tuberculosis in the European badger (Meles meles) after
      endobronchial inoculation of Mycobacterium bovis: I. Pathology and bacteriology.
AB  - The aim was to develop an endobronchial infection procedure for the study of
      Mycobacterium bovis infection in badgers. The badgers were anaesthetised and a
      cannula was passed per os to the tracheal bifurcation. When in place 1 ml of M.
      bovis suspension was inoculated. Three concentrations of M. bovis suspension were
      used; <10 colony forming units (cfu), approximately 10(2) cfu and approximately 3
      x 10(3) cfu. The badgers were examined at three weekly intervals for clinical
      signs of disease and a tracheal aspirate was collected at each examination. The
      badgers were euthanased 17 weeks post infection (pi) and at the post mortem
      examination a wide range of tissues were examined for gross and histopathological
      lesions of tuberculosis and cultured for M. bovis. A sample of bronchial alveolar
      lavage (BAL) fluid was collected at post mortem for culture. At post mortem
      examination 17 weeks after infection, gross and histopathological lesions of
      tuberculosis were observed in all badgers inoculated with the high and medium
      dose and 1/3 inoculated with the low dose. M. bovis was recovered from all
      inoculated badgers. Infection in the high dose group was more widely disseminated
      than in the other groups. The number of sites with gross and histopathological
      lesions increased with increasing dose of M. bovis. All tracheal aspirates were
      negative on culture and only one BAL, collected from a badger of the high dose
      group, was positive on culture. No clinical signs due to the experimental
      infection were observed. The endobronchial route of inoculation is an effective
      route for establishing experimental infection, and could be used for studies of
      tuberculosis pathogenesis, immunology of M. bovis infection in badgers and for
      challenging badgers in vaccine protection studies. Badgers appeared to be very
      susceptible to infection by this procedure even with a dose of < 10 cfu but
      appear to control and limit the resulting infection.

PMID- 17197005
TI  - Toxicokinetics of the active doxorubicin metabolite, doxorubicinol, in sulphur
      crested cockatoos (Cacatua galerita).
AB  - The pharmacokinetics of doxorubicinol, a cytotoxic metabolite of the anticancer
      drug, doxorubicin, were studied in four healthy sulphur-crested cockatoos
      (Cacatua galerita) after a 20 min intravenous infusion of 2 mg/kg. Plasma
      doxorubicinol concentrations were measured by HPLC. The pharmacokinetic
      parameters were estimated using a non-compartmental method. The mean (+/- SD)
      peak concentration was 8341 +/- 3132 microg/L at 17.5 +/- 5.0 min after the start
      of the infusion, and doxorubicinol concentrations declined biexponentially to
      154.3 +/- 34.5 microg/L, 40 min after the end of the infusion. Systemic clearance
      was 0.940 +/- 0.473 L/h/kg, mean residence time was 0.165 +/- 0.133 h, and steady
      state volume of distribution was 0.123 +/- 0.0526 L/kg. The terminal half-life
      was 0.660 +/- 0.611 h. Detectible but unquantifiable concentrations of
      doxorubicinol were present in the plasma ultrafiltrate of two birds during the
      infusion, indicating very extensive plasma protein binding. Physiological,
      haematological and biochemical monitoring over 3 weeks showed that doxorubicinol
      at a single infused dose of 2 mg/kg caused no toxicities of major concern.

PMID- 17197006
TI  - Antiretroviral therapy for children in the routine setting in Malawi.
AB  - Malawi is scaling up antiretroviral therapy (ART) for HIV-infected patients.
      Using a fixed-dose combination of stavudine+lamivudine+nevirapine ('Triomune') as
      the first-line regimen, split tablets are given to children with doses according
      to body weight. By March 2006, a total of 46 702 patients had been started on
      ART, of whom 2718 (5.8%) were children aged <15 years. In a subset of 935
      children, comprising 486 boys and 449 girls, 1.5% were aged <1 year, 26% were
      aged 1-4 years, 39% were aged 5-9 years and 33% were aged 10-14 years. Between
      July and September 2005, 7905 patients started ART, comprising 7469 adults and
      436 children. Six-month cohort outcomes censored on 31 March 2006 showed
      significantly more children alive and significantly fewer children dead or
      defaulted compared with adults. Between January and March 2005, 4580 patients
      started ART, comprising 4347 adults and 233 children. Twelve-month cohort
      outcomes censored on 31 March 2006 showed significantly more children alive
      compared with adults. The results of this national study should encourage other
      programmes to invest in ART for children and particularly to monitor their
      treatment outcomes.

PMID- 17197007
TI  - Time course of cholinesterase inhibition in adult rats treated acutely with
      carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl or propoxur.
AB  - To compare the toxicity of seven N-methyl carbamates, time course profiles for
      brain and red blood cell (RBC) cholinesterase (ChE) inhibition were established
      for each. Adult, male, Long Evans rats (n=4-5 dose group) were dosed orally with
      either carbaryl (30 mg/kg in corn oil); carbofuran (0.5 mg/kg in corn oil);
      formetanate HCl (10 mg/kg in water); methomyl (3 mg/kg in water); methiocarb (25
      mg/kg in corn oil); oxamyl (1 mg/kg in water); or propoxur (20 mg/kg in corn
      oil). This level of dosing produced at least 40% brain ChE inhibition. Brain and
      blood were taken from 0.5 to 24 h after dosing for analysis of ChE activity using
      two different methods: (1) a radiometric method which limits the amount of
      reactivation of ChE activity, and (2) a spectrophotometric method (Ellman method
      using traditional, unmodified conditions) which may encourage reactivation. The
      time of peak ChE inhibition was similar for all seven N-methyl carbamate
      pesticides: 0.5-1.0 h after dosing. By 24 h, brain and RBC ChE activity in all
      animals returned to normal. The spectrophotometric method underestimated ChE
      inhibition. Moreover, there was a strong, direct correlation between brain and
      RBC ChE activity (radiometric assay) for all seven compounds combined (r(2)=0.73,
      slope 1.1), while the spectrophotometric analysis of the same samples showed a
      poor correlation (r(2)=0.09). For formetanate, propoxur, methomyl, and
      methiocarb, brain and RBC ChE inhibitions were not different over time, but for
      carbaryl, carbofuran and oxamyl, the RBC ChE was slightly more inhibited than
      brain ChE. These data indicate (1) the radiometric method is superior for
      analyses of ChE activity in tissues from carbamate-treated animals (2) that
      animals treated with these N-methyl carbamate pesticides are affected rapidly,
      and recover rapidly, and (3) generally, assessment of RBC ChE is an accurate
      predictor of brain ChE inhibition for these seven pesticides.

PMID- 17197008
TI  - Modulation of insect Ca(v) channels by peptidic spider toxins.
AB  - Insects have a much smaller repertoire of voltage-gated calcium (Ca(V)) channels
      than vertebrates. Drosophila melanogaster harbors only a single ortholog of each
      of the vertebrate Ca(V)1, Ca(V)2, and Ca(V)3 subtypes, although its basal
      inventory is expanded by alternative splicing and editing of Ca(V) channel
      transcripts. Nevertheless, there appears to be little functional plasticity
      within this limited panel of insect Ca(V) channels, since severe loss-of-function
      mutations in genes encoding the pore-forming alpha1 subunits in Drosophila are
      embryonic lethal. Since the primary role of spider venom is to paralyze or kill
      insect prey, it is not surprising that most, if not all, spider venoms contain
      peptides that potently modify the activity of these functionally critical insect
      Ca(V) channels. Unfortunately, it has proven difficult to determine the precise
      ion channel subtypes recognized by these peptide toxins since insect Ca(V)
      channels have significantly different pharmacology to their vertebrate
      counterparts, and cloned insect Ca(V) channels are not available for
      electrophysiological studies. However, biochemical and genetic studies indicate
      that some of these spider toxins might ultimately become the defining
      pharmacology for certain subtypes of insect Ca(V) channels. This review focuses
      on peptidic spider toxins that specifically target insect Ca(V) channels. In
      addition to providing novel molecular tools for ion channel characterization,
      some of these toxins are being used as leads to develop new methods for
      controlling insect pests.

PMID- 17197009
TI  - The insecticidal potential of scorpion beta-toxins.
AB  - Voltage-gated sodium channels are a major target for toxins and insecticides due
      to their central role in excitability, but due to the conservation of these
      channels in Animalia most insecticides do not distinguish between those of
      insects and mammals, thereby imposing risks to humans and livestock. Evidently,
      as long as modern agriculture depends heavily on the use of insecticides there is
      a great need for new substances capable of differentiating between sodium channel
      subtypes. Such substances exist in venomous animals, but ways for their
      exploitation have not yet been developed due to problems associated with
      manufacturing, degradation, and delivery to the target channels. Engineering of
      plants for expression of anti-insect toxins or use of natural vectors that
      express toxins near their target site (e.g. baculoviruses) are still problematic
      and raise public concern. In this problematic reality a rational approach might
      be to learn from nature how to design highly selective anti-insect compounds
      preferably in the form of peptidomimetics. This is a complex task that requires
      the elucidation of the face of interaction between insect-selective toxins and
      their sodium channel receptor sites. This review delineates current progress in:
      (i) elucidation of the bioactive surfaces of scorpion beta-toxins, especially the
      excitatory and depressant groups, which show high preference for insects and bind
      insect sodium channels with high affinity; (ii) studies of the mode of
      interaction of scorpion beta-toxins with receptor site-4 on voltage-gated sodium
      channels; and (iii) clarification of channel elements that constitute receptor
      site-4. This information may be useful in future attempts to mimic the bioactive
      surface of the toxins for the design of anti-insect selective peptidomimetics.

PMID- 17197010
TI  - N-linked glycosylation of Gn (but not Gc) is important for Crimean Congo
      hemorrhagic fever virus glycoprotein localization and transport.
AB  - The mature Gn glycoprotein of Crimean Congo hemorrhagic fever (CCHF) virus
      contains two predicted glycosylation sites (557N and 755N). Of these, N-glycans
      are added only at 557N, as evidenced by abrogation of Gn-glycosylation by
      mutation of 557N but not 755N site. Mutational block of Gn-glycosylation at 557N
      did not significantly affect Gn proteolytic processing but did result in
      mislocalization and retention of Gn and other proteins synthesized from the virus
      M segment ORF (GP160, GP85, GP38 and Gc) in the endoplasmic reticulum. In
      contrast to Gn, similar mutational analysis demonstrated that, while N
      glycosylation occurs at the two predicted sites in Gc, abrogation of their
      glycosylation did not alter localization of any of the CCHF virus glycoproteins.
      Studies of Gn expressed in the absence of Gc demonstrate that, while Gn
      processing and localization are independent of Gc, all the CCHF virus
      glycoproteins appear dependent on N-glycosylation of Gn for correct folding,
      localization and transport.

PMID- 17197011
TI  - An assessment of estrogenic organic contaminants in Canadian wastewaters.
AB  - A suite of 30 primarily estrogenic organic wastewater contaminants was measured
      in several influent/effluent wastewater samples from four municipal wastewater
      treatment plants and effluents from one bleached kraft pulp mill (BKME) using an
      ultra-trace analytical method based on gas chromatography-high resolution mass
      spectroscopy (GC-HRMS). In vitro recombinant yeast assay detection of the
      estrogenic equivalent (EEq) on whole and solid phase extracted (SPE) and
      fractionated wastewater was also performed. 19-norethindrone was the most
      frequently detected and abundant (26-224 ng/L) of all the synthetic
      estrogens/progesterones in the influent samples. 17alpha-ethinylestradiol was the
      more frequently detected synthetic estrogen/progesterone in the effluents
      occurring at or below 5 ng/L with some sporadic occurrences of up to 178 ng/L.
      The greatest levels of steroidal estrogens in municipal effluents were E1>E2>E3
      which were all <20 ng/L. Nonylphenol and di(2-ethylhexyl) phthalate were found to
      be the highest non-steroidal synthetic compounds surveyed in both municipal
      influent and effluent samples, both occurring at 6-7 microg/L in municipal
      effluents. BKME contained relatively large amounts of the plant sterol
      stigmasterol (4 microg/L) but low amounts of fecal sterols, and steroidal
      estrogens (E2 only at 6 ng/L) when compared to the municipal effluents. In vitro
      EEq in the wastewater surveyed ranged from 9-106 ng E2/L and ranked from
      municipal influent>municipal effluent approximately BKME, with most of the
      estrogenicity fractionating in the 100% methanol SPE fraction followed by a
      secondary amount in the diethyl ether (for municipal) or methyl-tert butyl ether
      (for BKME) SPE fractions. Most correlations between chemical and in vitro
      estrogenic equivalency were weak (p>0.05 in most cases). Unexpected inverse
      correlations between in vitro estrogenic activity and concentrations of the
      estrogenic contaminant bisphenol A were found which likely contributed to the
      weakness of these correlations. A modified toxicity identification and evaluation
      procedure was continued with the SPE extracts from the more potent 100% methanol
      SPE fractions of municipal effluent. High performance liquid chromatography band
      elution retention times, based on in vitro estrogen detection, indicated that
      steroidal estrogens such as E2 were responsible for most of the estrogenicity of
      the samples. Subsequent collection and GC-MS analysis of active bands did not
      confirm the presence of steroidal estrogens, but expanded the possibility of
      phthalate esters (i.e. dibutyl phthalate) and natural sterols (i.e. beta
      sitosterol) contributing to the overall estrogenic load.

PMID- 17197012
TI  - Twelve-year experience in the management of endometrial cancer: a change in
      surgical and postoperative radiation approaches.
AB  - OBJECTIVE: Over the past 12 years, the primary management of endometrial cancer
      at a comprehensive cancer center has undergone changes characterized by the
      increased use of laparoscopic surgery with comprehensive staging resulting in a
      decreased reliance on postoperative adjuvant whole pelvic radiation therapy
      (WPRT). The purpose of this study was to analyze the results of these changes.
      MATERIALS AND METHODS: Between 1/93 and 12/04, 1312 patients underwent surgery
      for endometrial cancer consisting of either abdominal or laparoscopic
      hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO or LAVH/BSO). Pelvic and
      para-aortic lymph node dissection was performed at the discretion of the
      attending physician. Postoperative adjuvant treatment employed in patients with
      high-risk features consisted mainly of WPRT+/-intravaginal radiation therapy
      (IVRT). Total direct medical charges incurred from 10 days prior to surgery
      through 75 days after surgery were determined with charges converted to direct
      medical costs, taking into account inflationary changes. RESULTS: The median age
      at diagnosis for all patients was 62 years (range, 21-93 years), with a median
      follow-up of 31.6 months (range, 0-140 months). There was a significant increase
      in LAVH/BSO versus TAH/BSO (P<0.001) until 2001 when we began participating in a
      national randomized trial of laparoscopic versus abdominal surgery. In addition,
      there was a significant increase in the percentage of patients undergoing lymph
      node dissection as well as the median number of nodes removed (P<0.001). This was
      associated with a significant decrease in the use of WPRT during 1993-1998 versus
      1999-2004 (P<0.001). The use of IVRT remained the same during these time periods.
      There was no significant difference in 1-, 2-, or 5-year survival for patients
      treated in either time period. Cost data were available from 1995 to 2004. There
      was a significant increase in the median total direct medical costs when
      comparing periods 1995-1998 with 1999-2004 (P<0.001), although the median cost of
      pelvic radiation therapy was lower in the later time period. CONCLUSION: Over a
      12-year period, the primary management of endometrial cancer changed to include
      an increased use of laparoscopy and comprehensive surgical staging and a decrease
      in the use of postoperative adjuvant WPRT, with no appreciable negative effect on
      overall survival.

PMID- 17197013
TI  - A comparison of laparoscopic radical hysterectomy and pelvic lymphadenectomy and
      laparotomy in the treatment of Ib-IIa cervical cancer.
AB  - OBJECTIVE: To compare the feasibility, morbidity, and survival outcome of the
      laparoscopic radical hysterectomy and pelvic lymphadenectomy (LRH+LPL) with
      abdominal radical hysterectomy and pelvic lymphadenectomy (ARH+APL) for FIGO
      stage Ib-IIa cervical carcinoma. METHODS: The consecutive cases with FIGO Ib-IIa
      cervical cancer from August 1998 to December 2005 were documented, including 90
      patients underwent LRH+LPL, and 35 patients underwent ARH+APL as control group.
      The clinic data of perioperative periods and survival were compared between
      groups. RESULTS: In laparoscopy group the operating time increased significantly
      (262.99+/-67.6 min vs. 217.2+/-71.56 min, P=0.001), and the recovery time of
      bowel decreased significantly (1.96+/-0.62 days vs. 2.40+/-1.06 days, P=0.025).
      No significant difference was found between groups when the blood loss during
      operation (369.78+/-249.94 ml vs. 455.14+/-338.05 ml, P=0.125), numbers of the
      pelvic lymph nodes resected (21.28+/-8.39 vs. 18.77+/-9.47, P=0.151), recovery
      time of bladder function and postoperative hospital stays were compared. All
      laparoscopic procedures were completed successfully except 2 cases converted to
      laparotomy. The median follow-up was 26 months (range 5 to 84 months). Ten and
      five cases lost to follow-up in laparoscopy and laparotomy group, respectively.
      Excluding the lost cases, the recurrence rate (13.75% vs. 12%, P>0.05) and the
      mortality rate (10% vs. 8%, P>0.05) between groups was similar. CONCLUSION: Our
      data demonstrated that cervical cancer could be treated successfully with LRH+LPL
      with similar efficacy and recurrence rates to ARH+APL. LRH+LPL is a safe and
      effective alternative to conventional abdominal surgery for stage Ib-IIa cervical
      cancer, and should be used if the surgeon is sufficiently trained. Its clinical
      value should be confirmed by multicenter randomized clinic trials.

PMID- 17197014
TI  - Persistent exercise attenuates nicotine- but not clonidine-induced
      antinociception in female rats.
AB  - Exercise decreases the antinociceptive effects of opiate drugs. It has been
      hypothesized that the exercise-induced attenuation of opiate drug action is the
      result of the development of cross-tolerance between endogenous opioids released
      during exercise and exogenous opiates. The present study was designed to evaluate
      the role of exercise on non-opiate antinociception. Female Long-Evans rats were
      allowed ad lib access to running wheels. After 3 weeks, antinociceptive responses
      of animals were measured using the tail flick test following the administration
      of clonidine or nicotine. Nicotine and clonidine both produced dose-dependent
      increases in antinociceptive responses. Active animals were significantly less
      sensitive to nicotine-induced antinociception than inactive animals. There was no
      difference between the two groups in clonidine-induced antinociception. The
      results of these experiments suggest that exercise does not attenuate non-opioid,
      clonidine-induced antinociception. However, exercise does attenuate nicotine
      induced antinociception. Therefore, the effect of persistent exercise on
      analgesic drugs is not specific to opiates.

PMID- 17197015
TI  - Evaluation of a website-delivered computer-tailored intervention for increasing
      physical activity in the general population.
AB  - OBJECTIVE: To examine if a website-delivered physical activity intervention, that
      provides participants with computer-tailored feedback, can improve physical
      activity in the general population. METHODS: Healthy adults (n=434), recruited
      from parents and staff of 14 primary and secondary schools in Belgium in the
      spring of 2005, were allocated into one of two intervention groups (receiving
      intervention with or without repeated feedback) or a no-intervention control
      group. Physical activity-levels were self-reported at baseline and at 6 months
      (n=285), using a computerized long version of the International Physical Activity
      Questionnaire online. Repeated measures analysis of co-variances were used to
      examine differences between the three groups. RESULTS: Intent-to-treat analysis
      showed significant time by group interaction effects in favor of both
      intervention groups compared with the control group. Significant increases were
      found for active transportation (+20, +24, +11 min/week respectively) and leisure
      time physical activity (+26, +19, -4 min/week respectively); a significant
      decrease for minutes sitting on weekdays (-22, -34, +4 min/day respectively). No
      significant differences were found between both intervention groups. CONCLUSION:
      A website-delivered intervention, including computer-tailoring, was able to
      increase physical activity when compared to a no-intervention control group. High
      drop-out rate and the low number of participants who received repeated feedback
      indicated that engagement and retention are important challenges in e-health
      studies.

PMID- 17197016
TI  - Effect of composite temperature on in vitro intrapulpal temperature rise.
AB  - OBJECTIVES: To measure in vitro intrapulpal temperature when placing and
      restoring with either room-temperature or pre-heated (54 and 60 degrees C)
      composite. METHODS: A K-type thermocouple was placed in the pulpal chamber of an
      extracted, human bifurcated upper premolar which had a Class V preparation (1 mm
      remaining dentin thickness) on the facial surface. Tooth roots were immersed in a
      thermostatically controlled water bath and perfused with water at 1.25 microl/min
      to simulate physiological circulation in the pulp chamber. The thermocouple was
      connected to an analog-to-digital converter. The preparation was filled using
      composite either at room-temperature, or pre-heated to 54 or 60 degrees C with a
      commercial compule heater (Calset), using standard clinical procedures by one
      person while continuously monitoring intrapulpal temperature (n=5). Temperature
      rise over baseline values were determined at various stages during the
      restoration process: composite placement, contouring, prior to light-curing, and
      immediately after light-curing (20s, Optilux 501). At each measurement interval,
      intrapulpal temperature values were compared using ANOVA and the Tukey-Kramer
      post hoc test (alpha=0.05). RESULTS: Significant differences were found in
      intrapulpal temperature when comparing pre-heated and room-temperature composite
      treatments with respect to baseline among the stages of the restorative process.
      However, the extent of this increase with heated composite was only 0.8 degrees
      C. A 5 degrees C intrapulpal temperature rise was seen for all groups during
      photopolymerization. SIGNIFICANCE: Use of pre-heated composite only mildly
      increased intrapulpal temperature values when compared to composite delivered at
      room-temperature in an in vitro test environment. The largest temperature change
      occurred with application of the curing light.

PMID- 17197017
TI  - Initial osteoblast-like cell response to pure titanium and zirconia/alumina
      ceramics.
AB  - OBJECTIVES: Outstanding mechanical properties, resistance to scratching and high
      biocompatibility make zirconia/alumina ceramics interesting for dental
      applications. To solve the problem of the well-known low temperature degradation
      and to provide stable mechanical properties a novel zirconia alloy ((Y,Nb)
      TZP/alumina) was developed. The aim of this study was to investigate the initial
      bone cell response to this new zirconia/alumina composite ceramic. METHODS: HOS
      cells were cultured on zirconia/alumina composite (Zc) and pure titanium (Ti)
      discs. Surface topography was examined by atomic force microscopy (AFM), cell
      morphology by scanning electron microscopy (SEM). Cell proliferation (MTS) and
      alkaline phosphatase activity was measured at 1, 4 and 8 days. The mRNA
      expression of Cycline D1, the cell cycle regulating gene, integrin beta 1,
      osteonectin (ON) and beta-actin were evaluated by RT-PCR analysis after 12, 24
      and 48 h. RESULTS: Both substrates showed a very smooth character with R(a)
      values in the range of 0.002-0.113 microm supporting a continuous cellular
      growth. After 8 days, cell proliferation on Zc was higher than on Ti. The mRNA
      expression of cyclin D1 showed similar activity after 48 h on both surfaces, ALP
      activity was higher on Zc after 8 days. ON expression however showed no
      difference between the two groups. SIGNIFICANCE: Our data demonstrate that this
      new zirconia composite ceramic showed at least equivalent or slightly better
      biological response of osteoblast-like HOS cells than pure titanium during a
      short-time cell culture period.

PMID- 17197018
TI  - Influence of cation-pi interactions on RNA-binding proteins.
AB  - The energy contribution due to cation-pi interactions has been computed for 37
      RNA binding proteins. The contribution of these cation-pi interacting residues in
      sequential separation, secondary structure involvement, solvent accessibility,
      and stabilization centers has been evaluated. Sequential separation of the cation
      pi involving residues show that, long range contacts predominates in all the
      proteins studied. Lys and Arg prefers to be in helical structures. Of the cation
      pi interacting residues, Arg and Lys were in the exposed regions and the aromatic
      residues (Phe, Tyr and Trp) were in the buried and partially buried regions in
      the protein structures. Stabilization centers for these proteins showed that all
      the five residues found in cation-pi interactions are important in locating one
      or more of such centers. On the whole, the results presented in this work will be
      very useful for further investigations on the specificity and selectivity of RNA
      binding proteins and also for their structural studies.

PMID- 17197019
TI  - Folate-decorated poly(lactide-co-glycolide)-vitamin E TPGS nanoparticles for
      targeted drug delivery.
AB  - Doxorubicin-loaded nanoparticles (NPs) of vitamin E TPGS-folate (TPGS-FOL)
      conjugate and doxorubicin-poly(lactide-co-glycolide)-vitamin E TPGS (DOX-PLGA
      TPGS) conjugate were prepared by the solvent extraction/evaporation method for
      targeted chemotherapy of folate-receptor rich tumors. X-ray photoelectron
      spectroscopy demonstrated that folate was distributed on the NP surface while the
      drug molecules were entrapped in the NP matrix. The NPs were found of
      approximately 350nm diameter and exhibited a biphasic pattern of in vitro drug
      release. The cell uptake of the fluorescent NPs and the cell viability of the
      drug formulated in the NPs were quantitatively investigated, which were found
      dependent on the content of targeting TPGS-FOL conjugate. The NPs of 50% TPGS-FOL
      showed cellular uptake by MCF-7 cells 1.5 times higher and by C6 cells 1.7 times
      higher than the NPs with no TPGS-FOL component after 30min incubation. The MCF-7
      cell viability was found decreased significantly from 50.8% for the drug-loaded
      NPs of no TPGS-FOL to 8.2% for those of 50% TPGS-FOL after incubation at
      100microug concentration at 37 degrees C. The latter NPs also exhibited much
      lower IC(50) value than the DOX after 24h incubation, i.e., 19.4 vs. 43.7micror
      MCF-7 cells and 3.3 vs. >100micror C6 cells.

PMID- 17197020
TI  - Identification of tyrosines in the putative regulatory site of the Ca2+ channel
      TRPV6.
AB  - In HEK293 cells, transfected with the Ca2+ channel protein TRPV6, Ca2+ influx is
      increased and TRPV6 is tyrosine phosphorylated following addition of the tyrosine
      phosphatase inhibitor N,N-dimethyl-hydroxamido hydroxovanadate to cells. This
      effect of DMHV is enhanced by co-transfection of cells with the tyrosine kinase
      Src and the tyrosine phosphatase 1B. It is abolished when cells had been treated
      with PP1, an inhibitor of Src family tyrosine kinases. PTP1B interacts with the N
      terminal domain of TRPV6 within a region of amino acids 1-191 as shown by co
      immunoprecipitation, bimolecular fluorescence complementation and the yeast 2
      hybrid system. Point mutation of both tyrosines 161 and 162 in the TRPV6 protein
      abolishes the DMHV-effect on Ca2+ influx and tyrosine phosphorylation by Src.
      Single mutations of Y161 or Y162 shows that each of both tyrosines alone is
      sufficient for the DMHV-effect. We conclude that
      phosphorylation/dephosphorylation of tyrosines in position 161 and 162 is
      essential for regulation of Ca2+ influx through TRPV6 Ca2+ channels in HEK293
      cells.

PMID- 17197021
TI  - Erythroleukaemia, diabetes insipidus and hypophyseal damage: Two case reports.
AB  - We report on two cases of patients who developed diabetes insipidus (DI) before
      acute erythroleukaemia (EL). A brain MRI showed an empty sella turcica in one
      case and hypothalamo-hypophyseal peduncle damage in the second case. Reduced
      levels of TGF-beta1 and Vitamin D3, with associated EVI-1 over-expression and
      karyotypic abnormalities were documented. These two cases show specific
      chromosomal/molecular alterations in EL with DI. The hypothesis of pituitary
      involvement in erythroleukemogenesis is discussed.

PMID- 17197022
TI  - Prognostic impact of chromosomal alteration of 3q27 on nodal B-cell lymphoma:
      correlation with histology, immunophenotype, karyotype, and clinical outcome in
      329 consecutive patients.
AB  - Rearrangements involving the BCL6 gene are found in 30% of diffuse large B-cell
      lymphomas (DLBCLs). We evaluated the clinical characteristics and prognoses of
      patients with B-cell lymphoma carrying 3q27 translocations. Among the 59 patients
      having 3q27 translocation, 10.9% had follicular lymphoma (FL) and 23.1% had
      DLBCL. It is of interest that the prognostic significance was not found between
      FL and DLBCL with 3q27 translocations. Progression-free survival (PFS) rate was
      significantly higher in the FL patients with 3q27 translocation than in those
      with 18q21 translocation. PFS rate was significantly higher in the DLBCL patients
      with 3q27 translocation than in those with 18q21 translocation. These findings
      suggest that the presence of 3q27 translocation is a significant prognostic
      factor in DLBCL.

PMID- 17197023
TI  - PEG-Filgrastim activity on granulocyte functions.

PMID- 17197024
TI  - Innate immunity, assessed by plasma NO measurements, is not suppressed during the
      incubation fast in eiders.
AB  - Immunity is hypothesized to share limited resources with other physiological
      functions and may mediate life history trade-offs, for example between
      reproduction and survival. However, vertebrate immune defense is a complex system
      that consists of three components. To date, no study has assessed all of these
      components for the same animal model and within a given situation. Previous
      studies have determined that the acquired immunity of common eiders (Somateria
      mollissima) is suppressed during incubation. The present paper aims to assess the
      innate immune response in fasting eiders in relation to their initial body
      condition. Innate immunity was assessed by measuring plasma nitric oxide (NO)
      levels, prior to and after injection of lipopolysaccharides (LPS), a method which
      is easily applicable to many wild animals. Body condition index and
      corticosterone levels were subsequently determined as indicators of body
      condition and stress level prior to LPS injection. The innate immune response in
      eiders did not vary significantly throughout the incubation period. The innate
      immune response of eiders did not vary significantly in relation to their initial
      body condition but decreased significantly when corticosterone levels increased.
      However, NO levels after LPS injection were significantly and positively related
      to initial body condition, while there was a significant negative relationship
      with plasma corticosterone levels. Our study suggests that female eiders preserve
      an effective innate immune response during incubation and this response might be
      partially determined by the initial body condition.

PMID- 17197025
TI  - Molecular cloning, characterization, expression and functional analysis of
      Japanese flounder Paralichthys olivaceus Fas ligand.
AB  - We isolated and sequenced Fas ligand cDNA and its gene from Japanese flounder
      (JF), Paralichthys olivaceus. The JF-Fas ligand cDNA consisted of 1016 bp and
      encoded 230 amino acid residues. The identities of the deduced amino acid
      sequence of the JF-Fas ligand to human Fas ligand, Tumor necrosis factor-alpha
      and Lymphotoxin-alpha were 26.1%, 24.5% and 23.0%, respectively. A proline-rich
      domain (PRD) that is important for localization of the protein was found in the N
      terminal region, and two cysteine residues, which form a disulfide bond, were
      conserved. The JF-Fas ligand gene has a length of 1.8 kb and consists of four
      exons and three introns. The length of the JF-Fas ligand second intron is shorter
      than that in the human and pig Fas ligand genes. However, the organization of the
      exons and introns is similar to that of mammals. RT-PCR was conducted for 12
      tissues, and expression of JF-Fas ligand mRNA was detected in the kidney, thymus,
      gills, stomach and spleen. The recombinant JF-Fas ligand prepared in an
      Escherichia coli protein expression system showed cytotoxic activity against
      Japanese flounder cell line HINAE and caused the fragmentation of genomic DNA.
      The cytotoxic activity was measured by MTT assay. These results indicate that
      fish possess a Fas ligand system.

PMID- 17197026
TI  - Willingness to pay for cataract surgery in rural Southern China.
AB  - PURPOSE: To study willingness to pay for cataract surgery, and its associations,
      in Southern China. DESIGN: Cross-sectional willingness-to-pay interview
      incorporating elements of the open-ended and bidding formats. PARTICIPANTS: Three
      hundred thirty-nine persons presenting for cataract screening in Yangjiang,
      China, with presenting visual acuity (VA) < or = 6/60 in either eye due to
      cataract. METHODS: Subjects underwent measurement of their VA and a willingness
      to-pay interview. Age, gender, literacy, education, and annual income also were
      recorded. MAIN OUTCOME MEASURES: Maximum amount that the subjects would be
      willing to pay for cataract surgery. RESULTS: Among 325 (95.9%) subjects
      completing the interview, 169 (52.0%) were 70 years or older, 213 (65.5%) were
      women, and 217 (66.8%) had an annual income of <5000 renminbi (5000 = US 625
      dollars). Eighty percent (n = 257) of participants were willing to pay something
      for surgery (mean, 442+/-444 renminbi [US 55 dollars+/-55]). In regression
      models, older subjects were willing to pay less (8 renminbi [US 1 dollar] per
      year of age; P = 0.01). Blind subjects were significantly more likely (odds
      ratio, 5.7; 95% confidence interval, 1.7-19.3) to pay anything for surgery, but
      would pay on average 255 renminbi (US 32 dollars) less (P = 0.004). Persons at
      the highest annual income level (>10,000 renminbi [US 1250 dollars]) would pay 50
      dollars more for surgery than those at the lowest level (<5000 renminbi) (P =
      0.0003). The current cost of surgery in this program is 500 renminbi (US 63
      dollars). CONCLUSIONS: Sustainable programs will need to attract younger, more
      well-to-do persons with better vision, while still providing access to the
      neediest patients.

PMID- 17197027
TI  - Prevalence and long-term natural course of retinoschisis among elderly
      individuals: the Copenhagen City Eye Study.
AB  - PURPOSE: To characterize the prevalence and natural course of retinoschisis in a
      14-year follow-up study. DESIGN: Population-based cohort study. PARTICIPANTS:
      Nine hundred forty-six residents, aged 60 to 80 years, living in the Osterbro
      district of Copenhagen, participated in the prevalence study from 1986 to 1988.
      Excluding participants who died since baseline, 359 persons (97.3% of survivors)
      were reexamined after 14 years from 2000 to 2002. Of the 946 participants, 35
      persons had prevalent retinoschisis in 1 or both eyes at baseline and 15 of these
      persons were alive at follow-up. METHODS: Participants underwent an extensive
      ophthalmologic examination at Rigshospitalet, the National University Hospital of
      Copenhagen. Standardized protocols for the ophthalmologic examination included
      retinal evaluation by use of Goldmann's 3-mirror contact lens and ultrasonic B
      scan of the retina. Data for the 20 persons who died were obtained from the
      National Patient Register and the National Central Person Register. MAIN OUTCOME
      MEASURES: The prevalence, presence, disappearance, and progression of peripheral
      retinoschisis over a period of 14 years. RESULTS: The age-standardized prevalence
      of retinoschisis was 3.9% (95% confidence interval, 2.6-5.2) in persons aged 60
      to 80 years. Gender and increasing age at baseline were not associated with the
      presence of retinoschisis. The retinal quadrant of maximal involvement was the
      inferior temporal (44.4%). One case of symptomatic progressive retinal detachment
      occurred during follow-up (2.2%). This was preceded by cataract surgery. Four
      persons developed retinoschisis in the contralateral eye during follow-up;
      therefore, the incidence of retinoschisis was 16% and bilaterality was 57.1% at
      follow-up. However, in 14 persons (73.7%) the retinoschisis remained unchanged.
      The disappearance rate was 8.8% (n = 4). CONCLUSIONS: These findings indicate
      that senile retinoschisis primarily is bilateral, asymptomatic, and
      nonprogressive and should not be treated routinely. Cataract extraction is a
      possible risk factor for progressive retinal detachment.

PMID- 17197028
TI  - Efficacy and safety of latanoprost versus travoprost in exfoliative glaucoma
      patients.
AB  - OBJECTIVE: To evaluate 24-hour intraocular pressure (IOP) efficacy of latanoprost
      versus travoprost, each given every evening, in exfoliative glaucoma patients.
      DESIGN: Prospective, observer-masked, crossover comparison. PARTICIPANTS: Forty
      patients with exfoliation glaucoma. METHODS: Patients with a pressure of >24 mmHg
      were randomized to latanoprost or travoprost for an 8-week treatment period after
      a 6-week medicine-free period. Patients were then switched to the opposite
      treatment for the second period. At untreated baseline and at the end of each
      treatment period the IOP was measured at 6 am, 10 am, 2 pm, 6 pm, 10 pm, and 2
      am. MAIN OUTCOME MEASURE: Diurnal IOP. RESULTS: The mean 24-hour IOP was 25.1+/
      2.5 mmHg at baseline, 17.8+/-2.1 mmHg on latanoprost, and 17.3+/-2.2 mmHg on
      travoprost (P = 0.001). Individual time points were similar between treatments,
      except at 6 pm when travoprost provided lower IOP (16.7+/-2.6 vs 17.9+/-2.5 mmHg,
      P<0.001). Adverse events showed more conjunctival hyperemia with travoprost (n =
      15) than latanoprost (n = 6; P = 0.03). CONCLUSIONS: Latanoprost and travoprost
      both significantly reduce the 24-hour IOP from baseline in exfoliative glaucoma,
      but travoprost may demonstrate a greater hypotensive efficacy in the late
      afternoon.

PMID- 17197029
TI  - Theoretical investigations of the hydrolysis pathway of verdoheme to biliverdin.
AB  - Conversion of iron(II) verdoheme to iron biliverdin in the presence of OH(-) was
      investigated using B3LYP method. Both 3-21G and 6-31G* basis sets were employed
      for geometry optimization calculation as well as energy stabilization estimation.
      Calculation at 6-31G* level was found necessary for a correct spin state
      estimation of the iron complexes. Two possible pathways for the conversion of
      iron verdoheme to iron biliverdin were considered. In one path the iron was six
      coordinate while in the other it was considered to be five-coordinate. In the six
      coordinated pathway, the ground state of bis imidazole iron verdoheme is singlet
      while that for open chain iron biliverdin it is triplet state with 4.86 kcal/mol
      more stable than the singlet state. The potential energy surface suggests that a
      spin inversion take place during the course of reaction after TS. The ring
      opening process in the six-coordinated pathway is in overall -2.26 kcal/mol
      exothermic with a kinetic barrier of 9.76 kcal/mol. In the five-coordinated
      pathway the reactant and product are in the ground triplet state. In this path,
      hydroxyl ion attacks the iron center to produce a complex, which is only 1.59
      kcal/mol more stable than when OH(-) directly attacks the macrocycle. The
      activation barrier for the conversion of iron hydroxy species to the iron
      biliverdin complex by a rebound mechanism is estimated to be 32.68 kcal/mol.
      Large barrier for rebound mechanism, small barrier of 4.18 kcal/mol for ring
      opening process of the hydroxylated macrocycle, and relatively same stabilities
      for complexes resulted by the attack of nucleophile to the iron and macrocycle
      indicate that five-coordinated pathway with direct attack of nucleophile to the 5
      oxo position of macrocycle might be the path for the conversion of verdoheme to
      biliverdin.

PMID- 17197030
TI  - Towards bioreductively activated prodrugs: Fe(III) complexes of hydroxamic acids
      and the MMP inhibitor marimastat.
AB  - Fe(III)-salen (N,N-bis(salicylidene)-ethane-1,2-diimine) complexes of simple
      hydroxamic acids and the MMP (matrix metalloproteinase) inhibitor marimastat have
      been evaluated as hypoxia activated drug carriers. The aceto- (aha), propion-
      (pha), benzohydroxamato (bha), and marimastat complexes were prepared and
      characterised by single crystal X-ray diffraction and electrochemical analysis.
      The hydroxamato ligands form a bidentate chelate to Fe(III) with the remaining
      octahedral coordination sites occupied by the tetradentate salen ligand. Bonding
      of the hydroxamato ligands is in the typical motif of the majority of Fe(III)
      complexes in the literature. The reduction potentials of the complexes are of the
      order of -1300 mV (vs ferrocene/ferrocenium) and show partial reversibility in
      the re-oxidation waveforms of the cyclic voltammetry scans. This suggests that
      the Fe-salen carrier system would provide a suitably redox inert framework yet
      would release the ligands at hypoxic tumour sites upon reduction to the more
      labile Fe(II) oxidation state. Furthermore, biological testing of the marimastat
      complex established that these carriers are stable in non-reducing biological
      environments and would serve to deliver MMP inhibitors to tumour sites intact.

PMID- 17197031
TI  - The use of adjuvant granulocyte-macrophage colony-stimulating factor in HIV
      related disseminated atypical mycobacterial infection.
AB  - Mycobacterium avium complex (MAC) continues to be a challenging problem in some
      patients with advanced human immunodeficiency virus (HIV) infection despite the
      availability of potent chemotherapeutic agents. The use of adjunctive
      immunomodulatory therapy has shown promise in vitro, but there is currently
      limited supportive clinical evidence [Kemper CA, Bermudez LE, Derenski SC.
      Immunomodulatory treatment of Mycobacterium avium complex bacteraemia in patients
      with AIDS by use of recombinant granulocyte-macrophage colony-stimulating factor.
      J Infect Dis 1998;177:914-20; Kedzierska K, Johnson M, Mijch A, Cooke I, Rainbird
      M, Roberts S, et al. Granulocyte-macrophage colony-stimulating factor augments
      phagocytosis of Mycobacterium avium complex by human immunodeficiency virus type
      1 infected monocytes/macrophages in vitro and in vivo. J Infect Dis 2000;181:390
      94]. We report the resolution of MAC disease resistant to traditional therapy, in
      an HIV-infected individual, following the addition of granulocyte-macrophage
      colony-stimulating factor (GM-CSF).

PMID- 17197032
TI  - Synthesis and evaluation of polymeric continuous bed (monolithic) reversed-phase
      gradient stationary phases for capillary liquid chromatography and capillary
      electrochromatography.
AB  - There is a demand of novel high resolution separation media for separation of
      complex mixtures, particularly biological samples. One of the most flexible
      techniques for development of new separation media currently is synthesis of the
      continuous bed (monolithic) stationary phases. In this study the capillary format
      gradient stationary phases were formed using continuous bed (monolith)
      polymerization in situ. Different reversed-phase stationary phase gradients were
      tailored and their resolution using capillary liquid chromatography and capillary
      electrochromatography at isocratic mobile phase conditions was evaluated. It is
      demonstrated, that efficiency and resolution of the gradient stationary phases
      can be substantially increased comparing to the common (isotropic) stationary
      phases. The proposed formation approach of the gradient stationary phase is
      reproducible and compatible with the capillary format or microchip format
      separations. It can be easily automated for the separation optimizations or mass
      production of the capillary columns or chips.

PMID- 17197033
TI  - Detrimental effects of halothane narcosis on damage after endothelin-1-induced
      MCAO.
AB  - The influence of anaesthesia in experimental stroke research is controversial. We
      addressed this problem using the model of endothelin-1-induced occlusion of the
      middle cerebral artery (eMCAO). This model provided the opportunity to compare
      the infarct volumes of rats which were under halothane anaesthesia during eMCAO
      induction with the lesions of rats which were without anaesthesia during eMCAO.
      All animals were implanted with guide cannulae which allowed the induction of
      ischaemia in freely moving animals. For comparison, one group of animals was
      exposed to halothane during the induction of ischaemia. Seven days after eMCAO,
      the average infarct volume of halothane-anaesthetised rats was significantly
      larger than the lesion in freely moving animals. This difference was mainly due
      to increased cortical damage, whereas the striatum was much less influenced. The
      cortical infarct volume 21 days after induction of eMCAO under anaesthesia was
      significantly reduced compared to the infarct volume 7 days after eMCAO under
      anaesthesia. Our results indicate that halothane anaesthesia during eMCAO can
      cause a transient cortical increase in ischaemic infarct volume. The influence of
      volatile anaesthetics on ischaemic pathophysiology should be taken into
      consideration when preclinically testing potential neuroprotective drugs for
      clinical applications.

PMID- 17197034
TI  - A new technique for real-time analysis of caspase-3 dependent neuronal cell
      death.
AB  - Several markers are available to identify cells undergoing programmed cell death,
      but so far they are only applicable on fixed material. Therefore, no information
      on the kinetics of apoptosis can be obtained, although apoptosis is a dynamic
      cell process. Here, we describe a new technique that allows the real-time
      observation of the onset of apoptosis in primary neurons. Neurons are transfected
      with a plasmid that codes for a fluorescent protein localized in the soma. Upon
      activation of caspase-3, which represents the point-of-no-return in the apoptosis
      process, the fusion protein is cleaved and as a consequence translocates into the
      nucleus. The onset of apoptosis is thus visualized by translocation of the
      fluorescent signal from the soma to the nucleus. The translocation process was
      found to be specific for the apoptosis process as it correlates with the
      activation of caspase-3 and TUNEL staining. This tool does not require complex
      detection systems and allows for the first time the analysis of the kinetics of
      apoptosis in a simple and efficient manner.

PMID- 17197035
TI  - Increased left prefrontal activation in patients with unipolar depression: an
      event-related, parametric, performance-controlled fMRI study.
AB  - BACKGROUND: Executive deficits associated with frontal lobe dysfunction are
      prominent in depression. We applied a newly developed WM task to investigate the
      neural correlates of executive processes with functional magnetic resonance
      imaging (fMRI) at comparable performance levels analyzing correct trials only.
      METHODS: We studied 12 partially remitted, medicated inpatients meeting DSM-IV
      criteria for major depressive disorder and 17 healthy controls. We used a
      parametric version of a delayed match-to-sample WM task requiring manipulation of
      verbal material during a delay period in an event-related fMRI design. RESULTS:
      Depressed patients were generally slower and load-dependently less accurate than
      healthy controls. Patients showed significantly more activation of left
      dorsolateral prefrontal cortex with highest cognitive load. Additionally, they
      showed higher activation in ventromedial prefrontal cortex during the control
      condition. LIMITATIONS: The fact that patients were taking different
      antidepressant drugs could limit the explanatory power of the present results.
      CONCLUSIONS: Increased lateral prefrontal activation despite comparably
      successful performance - when only correct trials were analyzed - in patients
      with depression can be interpreted as evidence for compensatory recruitment of
      prefrontal cortical resources.

PMID- 17197036
TI  - Extrastriatal D2 and striatal D2 receptors in depressive illness: pilot PET
      studies using [11C]FLB 457 and [11C]raclopride.
AB  - BACKGROUND: Reduced dopaminergic function may occur in depressive disorders. In
      this paper the results of two pilot studies examining different aspects of the
      dopamine system in depression are presented. First, the binding of [(11)C]FLB 457
      to extrastriatal D(2) receptors was measured in a group of depressed patients.
      Second, the hypothesis that selective serotonin reuptake inhibiting (SSRI)
      antidepressants affect the striatal binding of [(11)C]raclopride was tested.
      METHODS: In the first study the binding of [(11)C]FLB 457 was compared between 7
      people with depression and 7 healthy controls. In the second study the binding of
      [(11)C]raclopride to striatal D(2/3) receptors was compared between 8 people
      taking SSRI antidepressant medication and 8 healthy controls. RESULTS: There was
      no difference in the binding of [(11)C]FLB 457 between the two groups.
      [(11)C]raclopride binding was reduced in the dorsal striatum of people taking
      antidepressants suggesting either that D(2/3) expression was reduced, or that
      dopamine release was increased, compared to untreated controls. LIMITATIONS: The
      depressed patients were not severely depressed and were not matched for gender
      with controls. In the raclopride group the patients and controls were not matched
      by gender and were taking different SSRI antidepressants. CONCLUSION: We found no
      support for the hypothesis that dopamine D(2) receptor expression is altered in
      extrastriatal brain regions in depression. SSRI antidepressants were associated
      with reduced [(11)C]raclopride binding in the dorsal striatum supporting the
      hypothesis that therapeutic effects of such drugs may, in part, be due to changes
      in the dopamine system.

PMID- 17197037
TI  - Association of polymorphisms in P2RX7 and CaMKKb with anxiety disorders.
AB  - BACKGROUND: There is considerable evidence that genetic factors play an important
      role in the pathophysiology of affective disorders including bipolar disorder,
      major depressive disorder and anxiety disorders. Long-term follow up studies as
      well as drug treatment studies suggest that these clinical conditions share a
      number of pathophysiological commonalities including genetic variables. One
      possible candidate region is located on chromosome 12q24.31, originated from
      previous linkage and association studies with bipolar disorder and unipolar
      depression. This region contains two candidate genes for purinergic ligand-gated
      ion channels, P2RX7 and P2RX4, and one gene coding for calmodulin-dependent
      protein kinase kinase b (CaMKKb). METHODS: In the present study, we investigated
      the genetic associations between 15 SNPs in the candidate genes P2RX7, P2RX4 and
      CaMKKb on chromosome 12q24.31 in 179 patients with anxiety disorders and
      syndromal panic attacks versus 462 healthy controls. RESULTS: One nominal case
      control association could be detected for a SNP in the 5'UTR region of P2RX4,
      which did not remain significant after correction for multiple testing. We found,
      however, a prominent association between severity of panic- and agoraphobia
      symptoms and an exonic SNP (rs3817190) in the CaMKKb gene and a trend for
      association with an exonic SNP in P2RX7 (rs1718119) with severity scores in the
      panic- and agoraphobia scale. CONCLUSION: The locus 12q24.31 seems to be an
      important genetic region for anxiety, bipolar and unipolar disorders, suggesting
      a genetic overlap in the group of affective disorders. The specific contribution
      of the herein reported gene polymorphisms to the clinical condition is still
      unclear and warrants further analysis.

PMID- 17197038
TI  - Immunostimulatory CpG oligodeoxynucleotides enhance the induction of bovine CD4+
      cytotoxic T-lymphocyte responses against the polymorphic immunodominant molecule
      of the protozoan parasite Theileria parva.
AB  - Enhancement of the induction of cytotoxic T-cell responses by immunostimulatory
      CpG oligodeoxynucleotides has been described in humans and mouse models. The
      present study attempted to address whether CpG has a similar effect in cattle.
      Immunisation of cattle with a recombinant form of the polymorphic immunodominant
      molecule from Theileria parva emulsified with immunostimulatory CpG
      oligodeoxynucleotides in adjuvant had no effect on the induction of antibody
      responses including the isotype profile, but significantly enhanced the induction
      of cytolytic responses that were mediated by CD4+CD3+ T cells utilizing the
      perforin-granzyme pathway.

PMID- 17197040
TI  - SLC26A4 mutations are associated with a specific inner ear malformation.
AB  - BACKGROUND AND AIM: Inner ear anomalies have been reported in approximately 30%
      of children with early onset deafness. Identification of causative genetic
      factors in a large proportion of these patients was not successful. Mutations in
      the SLC26A4 gene have been detected in individuals with enlarged vestibular
      aqueduct (EVA) or Mondini dysplasia. We aimed to characterize the inner ear
      anomalies associated with SLC26A4 mutations. METHODS: The SLC26A4 gene has been
      screened for mutations in 16 subjects from 14 unrelated Turkish families with a
      variety of inner ear anomalies ranging from Michel aplasia to incomplete
      partition-II and EVA. None of the patients was diagnosed to have a recognizable
      genetic syndrome. Additional four patients with Pendred syndrome from three
      families were included. RESULTS: Only one patient with EVA was found to have a
      heterozygous mutation (c.1586delT) in SLC26A4. All patients with Pendred syndrome
      had homozygous mutations and were noted to have either EVA or EVA associated with
      incomplete partition-II on the computed tomography of the temporal bone.
      CONCLUSION: SLC26A4 mutations are not associated with a large spectrum of inner
      ear anomalies. They, instead, result in a specific morphological appearance
      consistent with EVA or incomplete partition-II.

PMID- 17197039
TI  - Polyreactive myelin oligodendrocyte glycoprotein antibodies: Implications for
      systemic autoimmunity in progressive experimental autoimmune encephalomyelitis.
AB  - Two myelin oligodendrocyte glycoprotein (MOG92-106) monoclonal antibodies (mAbs)
      were produced from an A.SW mouse with progressive experimental autoimmune
      encephalomyelitis. Polyreactivity/specificity of the mAbs was demonstrated by
      ELISA. Functionality and a potential role in pathogenesis of systemic
      autoimmunity were demonstrated in vitro in a lymphocytotoxicity assay and in vivo
      upon injection into naive mice. Injection of MOG mAb producing hybridomas into
      naive mice resulted in immunoglobulin deposition in kidneys and liver. This model
      will be useful in determining whether transitional forms between CNS (organ)
      specific and systemic autoimmune diseases exist, and whether progressive multiple
      sclerosis has features of a systemic autoimmune disease.

PMID- 17197041
TI  - Immune responses to recombinant Mycobacterium smegmatis expressing fused core
      protein and preS1 peptide of hepatitis B virus in mice.
AB  - Attenuated strains of bacteria have been developed as potential live vectors to
      express homologous or heterologous antigens of many pathogens for inducing
      protective immune responses. The non-pathogenic and rapidly growing Mycobacterium
      smegmatis can be transformed effectively by genes for pathogenic antigens, and
      has been used as a valuable vector for the development of live vaccines. However,
      little is known on whether M. smegmatis could be transformed with the genes for
      HBV antigens and could express those genes, and whether vaccination with
      recombinant M. smegmatis could induce humoral and cellular immune responses in
      vivo. Both the core protein and preS1 peptide of the hepatitis B virus (HBV) are
      immunogenic and can induce cellular and humoral immune responses. This made them
      ideal platform for the development of new vaccines. In the present study, both
      recombinant M. smegmatis and DNA vaccines were generated to express the CS1
      antigen, a fusion protein that comprises truncated core protein (amino acids 1
      155) and preS1 peptide (amino acids 1-55) of HBV. Following vaccination of BALB/c
      mice with the live recombinant M. smegmatis, the CS1-based DNA vaccine, or
      controls, antigen-specific humoral and cellular immune responses were
      characterized. Vaccination with live recombinant M. smegmatis induced a stronger
      cellular immune response and a longer period of humoral immune response than with
      the DNA vaccination. These results indicate that the recombinant M. smegmatis can
      express efficiently immunogenic CS1 antigen of HBV in vivo, and may be used for
      the prevention of HBV infection.

PMID- 17197042
TI  - Development and validation of a non-radioactive DNA polymerase assay for studying
      cytomegalovirus resistance to foscarnet.
AB  - Phenotypic characterisation of the human cytomegalovirus (HCMV) pUL54 DNA
      polymerase is a useful tool for testing for mutations in the UL54 gene thought to
      render HCMV resistant to foscarnet. In this study, an in-house non-isotopic
      method for assessing polymerase enzymatic activity in the presence and absence of
      foscarnet was developed and its utility for HCMV polymerase phenotyping
      evaluated. Polymerase activity was assessed by monitoring the incorporation of
      digoxigenin-labelled nucleotides into the growing DNA chain and foscarnet
      concentrations inhibiting enzymatic activity by 50% were determined. HCMV DNA
      polymerases were synthesised in vitro by expression of UL54 under the control of
      the T7 promoter. Mutations of interest were introduced into the wild-type UL54
      gene by site-directed mutagenesis. Mutated polymerases and polymerases from HCMV
      reference strains were studied. The activity of polymerases containing mutations
      known to confer resistance to foscarnet (V715M, T700A and N495K) was inhibited by
      concentrations of foscarnet eight to 14 times higher than those required to
      inhibit wild-type polymerases. Our in-house non-radioactive phenotypic assay was
      sensitive and reproducible. It is also easy to perform and could provide a
      convenient method for characterising mutations conferring resistance to foscarnet
      in HCMV.

PMID- 17197043
TI  - Rescue of chimeric adenoviral vectors to expand the serotype repertoire.
AB  - The successful use of any adenoviral vectors is predicated upon the use of a
      serotype that is not neutralized by circulating antibodies. However, efforts to
      develop a diverse repertoire of serologically distinct adenovirus vectors may be
      hindered by the necessity to generate cell lines to allow for the successful
      propagation of vectors deleted of essential genes. A strategy to construct
      chimeric adenoviruses whereby the rescue and propagation of an E1-deleted HAdV-B
      derived adenoviral vector can be achieved using existing cell lines such as HEK
      293 is reported. It is further shown that this strategy may be more widely
      applicable.

PMID- 17197046
TI  - Isolated double-chambered right ventricle presenting in adulthood.
AB  - We report the case of a 55-year-old woman who was admitted for exertional chest
      pain with dyspnea. The patient was diagnosed with an isolated double-chambered
      right ventricle (DCRV) without associated congenital anomalies. Most cases of
      DCRV are diagnosed at a young age and commonly associated with VSD; isolated DCRV
      in adults is extremely rare.

PMID- 17197044
TI  - Adaptation of a ladder beam walking task to assess locomotor recovery in mice
      following spinal cord injury.
AB  - Locomotor impairments after spinal cord injury (SCI) are often assessed using
      open-field rating scales. These tasks have the advantage of spanning the range
      from complete paralysis to normal walking; however, they lack sensitivity at
      specific levels of recovery. Additionally, most supplemental assessments were
      developed in rats, not mice. For example, the horizontal ladder beam has been
      used to measure recovery in the rat after SCI. This parametric task results in a
      videotaped archival record of the event, is easily administered, and is
      unambiguously scored. Although a ladder beam apparatus for mice is available, its
      use in the assessment of recovery in SCI mice is rare, possibly because normative
      data for uninjured mice and the type of step misplacements injured mice exhibit
      is lacking. We report the development of a modified ladder beam instrument and
      scoring system to measure hindlimb recovery in vertebral T9 contusion spinal cord
      injured mice. The mouse ladder beam allows for the use of standard parametric
      statistical tests to assess locomotor recovery. Ladder beam performance is
      consistent across four strains of mice, there are no sex differences, and inter
      rater reliability between observers is high. The ladder beam score is
      proportional to injury severity and can be used to easily separate mice capable
      of weight-supported stance up to mice with consistent forelimb to hindlimb
      coordination. Critically, horizontal ladder beam testing discriminates between
      mice that score identically in terms of stepping frequency in open-field testing.

PMID- 17197045
TI  - Regulation of angiotensin II receptors levels during rat induced pulpitis.
AB  - A change in the microcirculatory hemodynamic is one of the most important events
      in inflammation. In the dental pulp, which is a connective tissue surrounded by a
      mineralized dentine substrate, disturbance in the blood flow as well as plasma
      extravasation may increase the pulp pressure and cause local ischemia. The
      octapeptide angiotensin II (AngII) regulates vascular tone and stimulates the
      release of pro-inflammatory cytokines by acting through the AT1 and AT2
      receptors. The AT1 receptor is responsible for the classical effects of AngII.
      The AT2 receptor is involved in other effects, such as vasodilation. Therefore,
      we aimed to evaluate the role of AT1 and AT2 receptors on the pulpal
      inflammation. The pulp tissue was mechanically exposed and after different
      periods the teeth were extracted and submitted to histopathological and RT-PCR
      analyses. The histological sections showed a number of congested and dilated
      blood vessels associated with a notable presence of inflammatory cells. RT-PCR
      data revealed that the AT1 receptor was down-regulated at 24 h after the pulp
      exposure. The AT2 receptor expression was up-regulated by a 9-hour period, and
      then decreased between 12- and 24-hour periods. It was demonstrated that the
      renin-angiotensin system plays an important role in the pulpal inflammation, with
      regulation of AngII receptor levels.

PMID- 17197047
TI  - Trait affect moderates cortical activation in response to state affect.
AB  - To examine the influence of trait affect on cortical activation during state
      affect, 32 healthy female participants viewed video clips to induce positive and
      negative emotional states. Frontal and parietal electroencephalogram (EEG) of the
      alpha band was assessed while participants imagined the scene of each video that
      generated the most intense emotions. The results showed that affect-induced
      frontal asymmetry was moderated by negative trait affect. The difference in
      frontal asymmetry between positive and negative state affect increased linearly
      with negative trait affect. Moreover, positive trait affect was negatively
      correlated with activation in the right-parietal brain region. These results
      suggest that trait affect moderates the effects of state affect on brain
      activation.

PMID- 17197048
TI  - The non-toxic A subunit of Shiga toxin type 1 prevents replication of bovine
      immunodeficiency virus in infected cells.
AB  - Shiga toxins are ribosome-inactivating proteins many of which are antiviral.
      Shiga toxin-producing Escherichia coli (STEC) may be pathogenic to humans, but
      are carried without ill effects by ruminants. We hypothesize that STEC have
      antiviral activity in ruminants, and showed previously that the non-toxic subunit
      A of Shiga toxin 1 (StxA1) acts selectively on cells infected with bovine
      leukemia virus, without harming normal cells, and that the numbers of intestinal
      STEC are inversely correlated with viral load in bovine leukemia virus-infected
      sheep. The purpose of the present study was to characterize StxA1 activity
      against a second bovine retrovirus, bovine immunodeficiency virus (BIV). Flow
      cytometry showed that StxA1 treatment induced apoptosis in BIV-infected cells but
      not in uninfected cells and immunoblot analysis showed that StxA1 curtailed
      synthesis of Gag p26 protein. A systematic electron microscopy description of BIV
      infection in fetal bovine lung fibroblasts showed an orderly sequence of changes
      in cell membrane, endoplasmic reticulum, Golgi, nucleus, and mitochondria, and
      suggested that the infected cells produce the virus within multivesicular bodies
      (MVBs). StxA1 interfered with all manifestations of BIV-induced transformation of
      infected cells into BIV-producing units. BIV-infected cells provided a suitable
      experimental system for investigation of the mechanism of Stx-antiviral activity.

PMID- 17197049
TI  - Differential sensitivity of viruses to the antiviral activity of Shiga toxin 1 A
      subunit.
AB  - The non-toxic enzymic A subunit of Shiga toxin 1 (StxA1) reduces expression and
      replication of the bovine retroviruses, bovine leukemia virus and bovine
      immunodeficiency virus (BIV). Here, the impact of StxA1 on representative
      positive and negative stranded RNA viruses was compared. BIV and equine
      infectious anemia virus were sensitive to picomolar concentrations of StxA1 while
      poliovirus, rhinovirus, and vesicular stomatitis virus were only marginally
      sensitive to nanomolar concentrations of toxin. Thus, the length of the
      reproductive cycle and/or other factors, but not viral encapsulation may play a
      role in determining sensitivity to StxA1. The effects of StxA1 at concentrations
      from 0.01 to 10 microg/ml on the most sensitive virus (BIV-infected cultures of
      fetal bovine lung cells) were analyzed by electron microscopy 48 h post
      challenge. Cells treated with 0.1 microg StxA1/ml or higher toxin concentrations
      were similar in appearance and showed progressively fewer viral factories with
      increasing toxin concentration. However, cells treated with 0.01 microg/ml StxA1
      had a radically different appearance, exhibiting smooth cell membranes and high
      vacuolization. These results showed that complex retroviruses were more sensitive
      to StxA1 than single-stranded RNA viruses and that StxA1 interfered with
      retroviral replication in a concentration-dependent manner.

PMID- 17197050
TI  - Bubble growth within the skin by rectified diffusion might play a significant
      role in sonophoresis.
AB  - Low frequency ultrasound has successfully been used for enhancing transdermal
      transport of a variety of different molecules. This phenomenon is referred to as
      sonophoresis. Several attempts have been made to investigate the enhancing
      mechanism in order to modulate the overall process. In this study we assess
      whether rectified diffusion is a process that occurs within the skin, which could
      eventually lead to channeling and thereby to transdermal sonophoresis. The model
      presented in this paper is based on the following postulate: gas bubbles are
      randomly distributed within the lipid bilayers of the stratum corneum (SC). As
      the skin is subjected to ultrasound, gas bubbles grow by rectified diffusion.
      During this period, bubbles may merge with the outer or inner boundaries of the
      SC, or merge with neighboring bubbles. Eventually, channels are created, allowing
      drugs to easily penetrate through the most significant barrier to transdermal
      delivery, the SC. As a result, transdermal transport rate is enhanced. In this
      work, a mathematical model has been formulated, in which permeability enhancement
      of the SC is linked to channels, possibly created by means of rectified
      diffusion. Sonophoresis may result from various mechanisms that act in synergy.
      The present model predicts that rectified diffusion might be one of the factors
      that lead to sonophoresis during ultrasound treatment.

PMID- 17197051
TI  - Batch RNAi selector: a standalone program to predict specific siRNA candidates in
      batches with enhanced sensitivity.
AB  - RNA interference (RNAi) is a popular and effective method for silencing gene
      expression. siRNAs should be gene-specific and effective to achieve specific and
      potent gene silencing. However, most currently available siRNA design programs
      are web-based programs that either require each sequence be submitted
      individually, making large-batch analyses difficult to conduct, or only provide
      limited options for searching off-target candidates (e.g. NCBI-BLAST). We have
      developed a stand-alone, enhanced RNAi design program that overcomes these
      shortcomings. We have implemented WU-BLAST, FASTA and SSEARCH homology searches
      for siRNA candidates to improve gene specific siRNA selection and to identity
      siRNA candidates that could lead to off-target gene silencing. We also included
      many new features such as siRNA score calculation and calculation of siRNA
      internal stability to help select highly potent siRNAs. This program is freely
      available for academic and commercial use (), and can be installed and run on any
      Linux machine. Our program automates the search for siRNAs and the resulting data
      files including a list of siRNA primers with scores and database search results
      for each siRNA candidate are stored locally for easy retrieval and inspection
      when needed.

PMID- 17197052
TI  - Transport of Sr2+ and SrEDTA2- in partially-saturated and heterogeneous
      sediments.
AB  - Strontium-90 has migrated deep into the unsaturated subsurface beneath leaking
      storage tanks in the Waste Management Areas (WMA) at the U.S. Department of
      Energy's (DOE) Hanford Reservation. Faster than expected transport of
      contaminants in the vadose zone is typically attributed to either physical
      hydrologic processes such as development of preferential flow pathways, or to
      geochemical processes such as the formation of stable, anionic complexes with
      organic chelates, e.g., ethylenediaminetetraacetic acid (EDTA). The goal of this
      paper is to determine whether hydrological processes in the Hanford sediments can
      influence the geochemistry of the system and hence control transport of Sr(2+)
      and SrEDTA(2-). The study used batch isotherms, saturated packed column
      experiments, and an unsaturated transport experiment in an undisturbed core.
      Isotherms and repacked column experiments suggested that the SrEDTA(2-) complex
      was unstable in the presence of Hanford sediments, resulting in dissociation and
      transport of Sr(2+) as a divalent cation. A decrease in sorption with increasing
      solid:solution ratio for Sr(2+) and SrEDTA(2-) suggested mineral dissolution
      resulted in competition for sorption sites and the formation of stable aqueous
      complexes. This was confirmed by detection of MgEDTA(2-), MnEDTA(2-), PbEDTA(2-),
      and unidentified Sr and Ca complexes. Displacement of Sr(2+) through a partially
      saturated undisturbed core resulted in less retardation and more irreversible
      sorption than was observed in the saturated repacked columns, and model results
      suggested a significant reservoir (49%) of immobile water was present during
      transport through the heterogeneous layered sediments. The undisturbed core was
      subsequently disassembled along distinct bedding planes and subjected to
      sequential extractions. Strontium was unequally distributed between carbonates
      (49%), ion exchange sites (37%), and the oxide (14%) fraction. An inverse
      relationship between mass wetness and Sr suggested that sandy sediments of low
      water content constituted the immobile flow regime. Our results suggested that
      the sequestration of Sr(2+) in partially-saturated, heterogeneous sediments was
      most likely due to the formation of immobile water in drier regions having low
      hydraulic conductivities.

PMID- 17197053
TI  - Associative learning and the control of human dietary behavior.
AB  - Most of our food likes and disliked are learned. Relevant forms of associative
      learning have been identified in animals. However, observations of the same
      associative processes are relatively scarce in humans. The first section of this
      paper outlines reasons why this might be the case. Emphasis is placed on recent
      research exploring individual differences and the importance or otherwise of
      hunger and contingency awareness. The second section briefly considers the effect
      of learning on meal size, and the author revisits the question of how learned
      associations might come to influence energy intake in humans.

PMID- 17197054
TI  - The control of bone remodeling by neuropeptide Y receptors.
AB  - An important role for the neuropeptide Y receptor system in the regulation of
      bone formation was recently revealed with a significant elevation in trabecular
      bone formation and bone volume following germline or hypothalamus-specific
      deletion of neuropeptide Y2 receptors in mice. Subsequent studies have now
      demonstrated that this central pathway is distinct from that of the other
      centrally regulated bone formation pathway mediated by leptin. This review
      discusses these recent findings and outlines how these new pathways could
      translate into potential novel targets for the treatment of bone disease.

PMID- 17197055
TI  - Gamma-hydroxybutyric acid induces oxidative stress in cerebral cortex of young
      rats.
AB  - GHB is a naturally occurring compound in the central nervous system (CNS) whose
      tissue concentration are highly increased during drug abuse and in the inherited
      deficiency of succinic semialdehyde dehydrogenase (SSADH) activity. SSADH
      deficiency is a neurometabolic-inherited disorder of the degradation pathway of
      gamma-aminobutyric acid (GABA). It is biochemically characterized by increased
      concentrations of gamma-hydroxybutyric acid (GHB) in tissues, cerebrospinal fluid
      (CSF), blood and urine of affected patients. Clinical manifestations are
      variable, ranging from mild retardation of mental, motor, and language
      development to more severe neurological symptoms, such as hypotonia, ataxia and
      seizures, whose underlying mechanisms are practically unknown. In the present
      study, the in vitro and in vivo effects of GHB was investigated on some
      parameters of oxidative stress, such as chemiluminescence, thiobarbituric acid
      reactive substances (TBA-RS), total radical-trapping antioxidant potential
      (TRAP), total antioxidant reactivity (TAR), as well as the activities of the
      antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPX) in homogenates from cerebral cortex of 15-day-old Wistar rats.
      In vitro, GHB significantly increased chemiluminescence and TBA-RS levels, while
      TRAP and TAR measurements were markedly diminished. In contrast, the activities
      of the antioxidant enzymes SOD, CAT and GPX were not altered by GHB in vitro.
      Acute administration of GHB provoked a significant enhance of TBA-RS levels and a
      decrease of TRAP and TAR measurements. These results indicate that GHB induces
      oxidative stress by stimulating lipid peroxidation and decreasing the non
      enzymatic antioxidant defenses in cerebral cortex of young rats. If these effects
      also occur in humans, it is possible that they might contribute to the brain
      damage found in SSADH-deficient patients and possibly in individuals who consume
      GHB or its prodrug gamma-butyrolactone.

PMID- 17197056
TI  - [Prevalence and description of hyponatremia in internal medicine departments of
      the France west area. A "one day" multicentric descriptive study].
AB  - PURPOSE: Few data are available on the prevalence and causes of hyponatremia in
      medical setting and to our knowledge, no recent descriptive study has been
      performed about hyponatremias in the French Departments of internal medicine.
      METHOD: A "one day" descriptive multicentric study was performed in the medicine
      departments of the France West area. A questionnaire was mailed to physicians who
      had to take part in a annual regional meeting about "hyponatremias", one month
      later. Hyponatremia was defined by a blood sodium level under the normal value of
      the local laboratory. Each internist had to precise for all hyponatremias in
      course at the study day, the exact value, the discovery circumstances, the
      mechanisms and etiologies, the associated diseases, the course and treatments.
      RESULTS: Seventy-four hyponatremias were identified. The overall prevalence was
      12,1%. The prevalence of severe hyponatremias (under 120 mmol/l) was 1,1%. These
      latter represented 9,4% of the whole hyponatremias (7/74). Associated symptoms
      and diseases, the mechanisms, the suspected etiologies, the course and treatments
      are described in detail. CONCLUSION: This multicentric study reports for the
      first time the prevalence, the clinical and etiological characteristics of
      hyponatremias coming from Internal Medecine Departments of the West area from
      France. The overall prevalence is lower in comparison with values usually
      reported in hospitalized patients, but the frequency of severe and moderate
      hyponatremias, the mechanisms and the suspected etiologies are identical to those
      reported in others countries.

PMID- 17197057
TI  - Modified LEAD System distractor to prevent tilting during alveolar distraction in
      the mandibular symphyseal region.
AB  - This report describes a simple modification of the LEAD System distractor that
      prevents tilting of the distractor rod, and consequent deviation of distraction
      direction, during alveolar distraction in the mandibular symphysis region.

PMID- 17197058
TI  - How much influence do women in Sweden have on caesarean section? A follow-up
      study of women's preferences in early pregnancy.
AB  - OBJECTIVE: to investigate factors associated with having a caesarean section,
      with special emphasis on women's preferences in early pregnancy. DESIGN: a cohort
      study using data from questionnaires in early pregnancy and 2 months after
      childbirth, and data from the Swedish Medical Birth Register. SETTING: women were
      recruited from 97% of all antenatal clinics in Sweden at their booking visit
      during 3 weeks between 1999 and 2000, and followed up 2 months after birth.
      PARTICIPANTS: a total of 2878 Swedish-speaking women were included in the study
      (87% of those who consented to participate and 63% of all women eligible for the
      study). FINDINGS: Of 236 women who wished to have their babies delivered by
      caesarean section when asked in early pregnancy, 30.5% subsequently had an
      elective caesarean section and 14.8% an emergency caesarean section. The logistic
      regression analyses showed that, a preference for caesarean section in early
      pregnancy (odds ratio [OR] 9.63, 95% confidence interval [CI] 5.94-15.59), a
      medical diagnosis (OR 9.03, 95% CI 5.68-14.34), age (OR 1.08, 95% CI 1.03-1.13),
      parity (OR 0.58, 95% CI 0.37-0.91), a previous elective caesarean section (OR
      15.11, 95% CI 6.83-33.41) and a previous emergency caesarean section (OR 18.29,
      95% CI 10.00-33.44) was associated with having an elective caesarean section.
      Having an emergency caesarean section was associated with a preference for a
      caesarean section (OR 2.59, 95% 1.61 to 4.18), a medical diagnosis (OR 4.12, 95%
      CI 2.91-5.88), age (OR 1.08, 95% CI 1.05-1.12), primiparity (OR 3.34, 95% CI 1.78
      6.27), a previous emergency caesarean section (OR 10.69, 95% CI 6.03-18.94), and
      a previous elective caesarean section (OR 7.21, 95% CI 2.90-17.92). KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: a woman's own preference about
      caesarean section was associated with the subsequent mode of delivery. Asking
      women about their preference regarding mode of delivery in early pregnancy may
      increase the opportunity to provide adequate support and possibly also to reduce
      the caesarean section rate.

PMID- 17197059
TI  - An Australian perspective of fatherhood and sexuality.
AB  - OBJECTIVE: to describe and explore the effect that pregnancy, childbirth and
      adjustment to a new baby have on the sexual relationship of fathers. DESIGN: a
      content analysis, using a qualitative approach, was undertaken on the written
      comments provided by fathers on a 6-week postpartum postal survey. The survey was
      undertaken to provide information relating to fathers' adaptation to fatherhood.
      The father's functional status was measured using, the Inventory of Functional
      Status-fathers (IFS-F) Tool. SETTING: a regional location within New South Wales,
      Australia. Participants (fathers) were recruited through postnatal services
      within hospital and community settings. PARTICIPANTS: volunteer study
      participants consisting of 204 fathers were sent a questionnaire at 6 weeks
      postpartum. The questionnaire was returned by 128 study participants (fathers).
      The participants were men experiencing fatherhood for the first time or who were
      adding to their existing families. FINDINGS: comments by the study participants
      revealed that sexual relationships during pregnancy and the postnatal period
      undergo a variety of changes that may affect the couple's relationship. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: it is important for health-care
      professionals, particularly midwives, to recognise that variance in sexual
      activity during the childbearing period does occur, and that there is a need for
      the midwife to be open to individual discussion of sexual activity with the woman
      and her partner during pregnancy and postnatal periods. Holistic care of women
      and their partners in the childbearing period requires health professionals to
      effectively communicate current information and education on sexuality.

PMID- 17197060
TI  - A cross-sectional study of knowledge and practice of pelvic floor exercises
      during pregnancy and associated symptoms of stress urinary incontinence in North
      East Scotland.
AB  - OBJECTIVES: to establish levels of knowledge about pelvic floor exercises during
      pregnancy; reported practice of pelvic floor exercises in pregnancy; and
      prevalence of stress urinary incontinence in a sample of women in the third
      trimester of pregnancy. DESIGN: structured cross-sectional interview survey.
      PARTICIPANTS: pregnant women over the age of 16 years and more than 30 weeks
      gestation attending antenatal clinics in North-East Scotland. Of 350 women who
      agreed to participate, 289 (82.6%) were interviewed between July 1999 and March
      2000. FINDINGS: 225 women (77.9%) reported being given or obtaining information
      about pelvic floor exercises in the current pregnancy. Books were the most
      frequently mentioned source of information. Midwives were the health
      professionals most likely to give information about pelvic floor exercises.
      Younger women, first-time mothers and those from more deprived backgrounds were
      less likely to report having information about the exercises. A third of women
      (n=90, 31.1%) said that they would have liked more information about the
      exercises. Practice of the exercises during pregnancy was reported by just over
      half the sample (n=156, 54.0%) and more than once a day by 26.3% (n=76). Younger
      women, and those from more deprived backgrounds, were less likely to report the
      practice of exercises. No difference was found in reported practice according to
      parity. More than half (n=157, 54.3%) of the women reported incontinence during
      the current pregnancy. No relationship was found between reported practice of
      pelvic floor exercises and stress urinary incontinence. KEY CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: the number of women who indicated a desire for more
      information and the low number who reported practice of the exercises suggest
      that improvements could be made. The gaps in information provision and practice
      suggest areas for future health promotion about the exercises, particularly by
      midwives, as not all women are seen by a physiotherapist during pregnancy.
      Reported levels of incontinence during pregnancy confirm previous findings and
      highlight the prevalence of incontinence in pregnancy.

PMID- 17197061
TI  - Baby Friendly Hospital Initiative practices and breast feeding duration in a
      cohort of first-time mothers in Adelaide, Australia.
AB  - OBJECTIVE: to investigate the relationship between adherence to six of the Baby
      Friendly Hospital Initiative (BFHI) Ten steps to successful breast feeding and
      the duration of breast feeding in first-time mothers. DESIGN: a prospective study
      to assess the duration of breast feeding up to 6 months postpartum. Survival
      analysis techniques (Kaplan-Meier curves and Cox proportional hazard models) were
      used to interpret the data. PARTICIPANTS: 317 women who had given birth to their
      first baby (at term) in a large teaching maternity hospital in Adelaide, South
      Australia, during the period March to November 2003. FINDINGS: ignoring all other
      factors, we found that women whose babies received a bottle feed, used a pacifier
      or dummy, or who used a nipple shield during their postnatal stay, were at
      significantly greater risk of weaning (p0.05). After adjusting for socio
      demographic variables, self-efficacy, intended duration of breast feeding, and
      method of delivery, the results unexpectedly showed that the only significant
      predictor of early weaning was breast feeding on demand. However, a composite
      variable indicating use of one or more of nipple shields, a dummy or bottle feeds
      while in hospital resulted in a significantly greater risk of weaning (p=0.05).
      IMPLICATIONS FOR PRACTICE: socio-demographic and cultural factors may be more
      important determinants of the duration of breast feeding than some of the very
      specific hospital practices targeted in the Ten steps to successful breast
      feeding. From a public health perspective, we may influence the duration of
      breast feeding through better post-discharge support services, or through
      interventions that improve attitudes to breast feeding in specific socio-cultural
      and economic groups.

PMID- 17197062
TI  - Predicting stress in pre-registration midwifery students attending a university
      in Northern England.
AB  - OBJECTIVE: to determine which variables predict stress (psychological distress)
      in pre-registration midwifery students. DESIGN: a cross-sectional survey, using a
      range of self-report measures bound together in a 'questionnaire pack'. SETTING:
      the study reported here is taken from a wider investigation into stress among
      nursing and midwifery students, undertaken in the nursing and midwifery
      department of a large university in Northern England. PARTICIPANTS: 120 pre
      registration midwifery students pursuing one of three diploma programmes:
      'standard', 'enhanced' and 'short'. MEASUREMENTS: multivariate logistic
      regression was used as the analytical technique. The variables used in the
      analyses undertaken were all derived from formal and study-specific, self-report
      measures included in the questionnaire pack. 'Stress' (whether a participant was
      psychologically distressed or not) was obtained via the General Health
      Questionnaire. Potential predictors of stress were collected from two formal
      measures (the Student Nurse Stress Index and the Coping Inventory for Stressful
      Situations) and from questions in the questionnaire pack designed to elicit
      demographic data and data of specific interest to nurse and midwife educators.
      FINDINGS: 102 questionnaire packs (85%) were returned. The prevalence of stress
      among participants was over 40%. A series of logistic regression analyses
      resulted in five competing regression models. Through a systematic selection
      process, two of these models were chosen for discussion. These models suggested
      that the key predictors of psychological distress in the population studied were
      self-report of stress levels, the type of midwifery programme being pursued, the
      use of 'task-oriented' coping and, possibly, whether or not a student smokes
      cigarettes. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: despite the prevalence
      rate of 40%, the prevalence of stress among midwifery students is generally no
      better or worse than that of other students or of qualified health-care
      professionals. Those involved in midwifery education need to know how to manage
      student stress effectively. This can be achieved by ensuring that personal
      teachers (continue to) play a key role in supporting students, especially when
      students self-report high levels of stress. Incorporating formal stress
      management training into pre-registration midwifery programmes may also be
      useful. Sound knowledge of the issues associated with student stress during
      curriculum design, however, may ultimately prove to be the most effective way of
      managing student stress. In a discipline such as midwifery, these issues are as
      divergent as the politics of midwifery, the processes used in recruitment and
      selection, the role of women in society, and the nature, quality and quantity of
      the learning experiences and the assessment strategies used.

PMID- 17197064
TI  - Grip strength and forearm circumference in a healthy population.
AB  - Two hundred and fifty subjects were recruited. Age, sex, hand preference and
      anthropometric measurements were recorded for each subject. Grip strength was
      measured using a Jamar hydraulic dynamometer. Multiple regression analyses were
      performed. One hundred and seventy two subjects were men and 78 were women.
      Twenty-six subjects were left hand dominant. Hand grip strength was greatest for
      the 35 to 44 year old group for both sexes. Grip strength was consistently
      greater for men than women. Contralateral grip strength predicted maximum grip
      strength for both sexes. Forearm circumference predicted maximum hand grip
      strength for men. Although there was a large range of forearm circumferences in
      the population, there was little difference between sides for each subject (100%
      less than 2 cm). The demonstrated relationships between: (i) contralateral grip
      strengths and (ii) grip strength and forearm circumference lead us to suggest
      that for certain pathologies, a difference in forearm circumference greater than
      2 cm may lend credence to a measurement of diminished grip strength.

PMID- 17197065
TI  - Anterior tenoarthrolysis for severe flexion contracture of the fingers (the
      "TATA" operation): a review of 50 cases.
AB  - The "hook finger", with both proximal interphalangeal (PIP) and distal
      interphalangeal (DIP) joint flexion contractures, often after multiple previous
      operations, is difficult to treat. This paper reports the results of 50 fingers
      in 49 patients in which the TATA (Teno-Arthrolyse Totale Anterieure) salvage
      procedure, described by Saffar in 1978, was carried out. Thirty-seven of 50 (74%)
      of these fingers had had at least one previous operation, most on the flexor
      apparatus. The mean PIP and DIP extension deficit pre-operatively was 133 degrees
      with a mean PIP lag of extension of 83 degrees . With a mean follow-up of 7.8
      years, 45 fingers were improved, five were not and none was worsened. The mean
      PIP and DIP extension deficit postoperatively was 47 degrees , with a mean PIP
      lack of extension of 31 degrees . The overall gain in extension deficit of both
      joints was 86 degrees and of the PIP was 52 degrees . One PIP joint developed
      septic arthritis immediately after surgery. The benefit of this salvage operation
      is mainly in the change of the active range of motion to a more functional arc.

PMID- 17197066
TI  - Re: Grading of radiographic osteolytic changes after silastic metacarpophalangeal
      arthroplasty and a prospective trial of osteolysis following use of Swanson and
      Sutter prostheses.

PMID- 17197067
TI  - Altered glucose homeostasis and oxidative impairment in pancreas of rats
      subjected to dimethoate intoxication.
AB  - The primary objective of this study was to investigate the effect of repeated
      sublethal doses of dimethoate (DM), an organophosphorus insecticide on glucose
      homeostasis, oxidative stress induction in pancreas and pancreatic damage in
      adult rats. Daily oral administration of DM (20 and 40 mg/kg b.w.) for 30 days
      induced a significant increase in blood glucose levels which was associated with
      impaired glucose tolerance. DM treatment resulted in elevated levels of
      pancreatic tissue specific markers such as activities of amylase and lipase in
      serum and pancreatic tissue indicating pancreatic dysfunction. Further, the
      activities of DT-diaphorase and NADPH-diaphorase in pancreas of DM treated rats
      were also found to be elevated. Interestingly, these biochemical dysfunctions
      were accompanied by a marked dose-related enhancement of lipid peroxidation and
      ROS levels in the pancreatic tissue indicating significant induction of oxidative
      damage. Additional evidence such as depletion in reduced glutathione levels and
      significant alterations in enzymic antioxidant defenses in pancreas among DM
      treated rats suggested induction of oxidative stress. Taken together, these
      findings provide experimental evidence that dimethoate at subchronic oral doses
      has the propensity to impair glucose homeostasis, induce significant pancreatic
      damage and also provide an account of the associated oxidative damage to
      pancreatic tissue in adult rats.

PMID- 17197068
TI  - In situ tracing the process of human enamel demineralization by electrochemical
      impedance spectroscopy (EIS).
AB  - OBJECTIVE: The purpose of this study was to in situ characterize the
      demineralization (namely dissolution of hydroxyapatite) on the surface of the
      human enamel using electrochemical impedance spectroscopy (EIS) technology.
      METHODS: Fresh human third molars extracted without visible evidence of caries,
      were used in this study. After they were immersed in a demineralizing solution
      prepared from lactic acid and carboxy methyl cellulose sodium (Na-CMC) buffering
      at pH 4, demineralization happened on their surfaces. EIS of the specimens were
      measured at a series of immersed interval. X-ray diffractometer (XRD) were used
      to distinguish the microstructure of the surface layer of the specimens. The
      depositions that appeared in the demineralizing solution after 46 h immersion
      were analyzed by fourier transform infrared spectrometer (FTIR). RESULTS: XRD
      analysis revealed that the percentage of intensity (I%) of HAP gradually
      decreased with the elapsed immersing time, which indicated the dissolution of HAP
      columns of enamel. Nyquist spectra were fitted with an equivalent circuit
      characterized by some parameters, such as Q and R(p) (error<0.1%). Changes of the
      parameters' values revealed that the rate of demineralization accelerated at the
      forepart of the demineralization, but slowed down beyond 70 h immersion.
      CONCLUSIONS: The results suggested that EIS was proved to be a useful method for
      in situ investigating and in vivo detecting the demineralization of the enamel.

PMID- 17197069
TI  - Comment on "Pregnancy outcome after early detection of bacterial vaginosis" [Eur.
      J. Obstet. Gynecol. Reprod. Biol. 128 (2006) 40-45].

PMID- 17197070
TI  - Laparoscopic live donor right nephrectomy: a new technique to maximize the length
      of the renal vein using a modified Endo GIA stapler.
AB  - OBJECTIVES: To report the utilization of a modified Endo GIA vascular stapler to
      obtain the full length of the renal vein during transperitoneal laparoscopic live
      donor right nephrectomy. METHODS: We used a modified Endo GIA stapler, in which
      the triple staggered rows of staples were removed from the kidney donor side to
      obtain the full length of the right renal vein. This technique has currently been
      used in nine consecutive transperitoneal laparoscopic right donor nephrectomies.
      RESULTS: With this technique, the entire right renal vein length was harvested in
      all cases, without vascular complications. Mean renal warm ischemia time from
      clamping of the renal vessels to cold perfusion was 135s, and mean receptor
      postoperative glomerular filtration rate after 30 d was 67.3 ml/min. There were
      no graft losses. CONCLUSIONS: A novel technique for laparoscopic live donor right
      nephrectomy is described. It allows harvesting the full length of the right renal
      vein in a safe and feasible way without compromising warm ischemia time.

PMID- 17197071
TI  - Methods of calculating prostate-specific antigen velocity.
AB  - OBJECTIVES: Numerous methods of calculating PSA velocity (PSAV) are used and have
      the potential to produce differing PSAV results from the same PSA data. We
      calculated PSAV using three common methods and compared differences between the
      methods and their predictive value for prostate cancer diagnosis. METHODS: From a
      population-based database of PSA results, men with initial PSA<10.0 ng/ml and a
      subsequent diagnosis of prostate cancer or benign histology were identified.
      Those with > or =3 PSA tests before diagnosis carried out over a minimum of 18 mo
      were included. PSAV was calculated by using three methods: The differences
      between the methods and test characteristics of each method were compared.
      RESULTS: Of the 2204 men included, 716 (32.5%) were diagnosed with prostate
      cancer and 1488 (67.5%) benign histology. PSAV differed markedly in each method
      of calculation. The LR and FL methods had similar predictive values, which were
      higher than the AE method. There was strong agreement for cancer diagnosis
      between LR and FL (kappa=0.85), with weaker agreement between LR/AE and FL/AE
      (kappa=0.69 and 0.66, respectively). CONCLUSIONS: Methods used to calculate PSAV
      using the same PSA data can produce markedly different results. Linear regression
      should be the method of choice for calculating PSAV. Using first and last PSA
      values only may be adequate for everyday clinical use, as long as measurements
      are separated by a sufficiently long time period.

PMID- 17197072
TI  - Analysis of a Schnute postulate-based unified growth model for model selection in
      evolutionary computations.
AB  - In order to evaluate the feasibility of a combined evolutionary algorithm
      information theoretic approach to select the best model from a set of candidate
      invasive species models in ecology, and/or to evolve the most parsimonious model
      from a suite of competing models by comparing their relative performance, it is
      prudent to use a unified model that covers a myriad of situations. Using
      Schnute's postulates as a starting point [Schnute, J., 1981. A versatile growth
      model with statistically stable parameters, Can. J. Fish Aquat. Sci. 38, 1128
      1140], we present a single, unified model for growth that can be successfully
      utilized for model selection in evolutionary computations. Depending on the
      parameter settings, the unified equation can describe several growth mechanisms.
      Such a generalized model mechanism, which encompasses a suite of competing
      models, can be successfully implemented in evolutionary computational algorithms
      to evolve the most parsimonious model that best fits ground truth data. We have
      done exactly this by testing the effectiveness of our reaction-diffusion
      advection (RDA) model in an evolutionary computation model selection algorithm.
      The algorithm was validated (with success) against field data sets of the Zebra
      mussel invasion of Lake Champlain in the United States.

PMID- 17197074
TI  - Functional in vitro characterisation of the androgen receptor GGN polymorphism.
AB  - Superior androgen receptor (AR) function in subjects carrying a GGN repeat length
      of 23 (GGN23) has been indicated in vivo. Therefore, the activity of the AR
      carrying GGN23 combined with CAG22 was compared to the AR with GGN10, 24 and 27,
      respectively, in the presence of 0.1-100 nM testosterone or DHT. At 100 nM DHT,
      GGN24 showed 35% lower transactivating activity (95% [CI]: 20-50%) than GGN23.
      GGN10 and GGN27 also showed significantly less AR activity than GGN23 (mean
      differences [95% CI]: 54% [40-68%] and 58% [39-78%], respectively). The same
      trend was also observed at lower DHT concentrations. In response to R1881, GGN23
      activity was significantly higher than for other lengths. ARs with other
      glutamine numbers than 23 have lower transactivating capacity in response to both
      testosterone and DHT. Congenital malformations and other signs of hypoandrogenism
      in subjects with AR gene GGN lengths other than 23 could, hence, be related to a
      lower AR activity.

PMID- 17197075
TI  - Curcumin inhibits the formation of capillary-like tubes by rat lymphatic
      endothelial cells.
AB  - The natural pigments curcumin and berberine have been shown to exhibit a variety
      of pharmacologic effects including anti-inflammatory, anti-cancer, and anti
      metastatic properties. Here, we investigated the anti-lymphangiogenic effect with
      an in vitro tube-forming model using conditionally immortalized lymphatic
      endothelial TR-LE cells, a newly established cell line originating from the
      thoracic duct of a transgenic rat expressing the temperature-sensitive SV40 large
      T-antigen. Curcumin, but not berberine, exhibited a dose-dependent inhibition of
      the formation of capillary-like tubes by TR-LE cells without affecting cell
      viability and adhesion to Matrigel. To address the molecular mechanisms involved,
      we performed experiments with specific inhibitors against putative targets of
      curcumin, including IkappaB kinase (IKK), epidermal growth factor receptor
      (EGFR), phosphatidylinositol-3 kinase (PI3K)/Akt, and matrix metalloproteinases
      (MMPs). While the IKK-2 inhibitor VI and EGFR tyrosine kinase inhibitors
      gefitinib and PD153035 had no effect, both the PI3K inhibitor LY294002 and the
      MMP inhibitor GM6001 shortened the tubes by approximately 50%. Western blot
      analysis and gelatin zymography revealed that curcumin, but not berberine, has an
      inhibitory effect on the phosphorylation of Akt and enzymatic activity of MMP-2
      in TR-LE cells. These results suggest that curcumin exerts its inhibitory effect
      on lymphangiogenesis partly through Akt and MMP-2.

PMID- 17197073
TI  - Differential expression of HPA axis homolog in the skin.
AB  - Human skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis
      including pro-opiomelanocortin (POMC), corticotropin releasing hormone (CRH), the
      CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes
      glucocorticoids. Expression of these elements is organized in functional, cell
      type-specific regulatory loops, which imitate the signaling hierarchy of the HPA
      axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates
      POMC expression and production of ACTH through activation of cAMP dependent
      pathway(s). Melanocytes respond with enhanced production of cortisol and
      corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH
      and ACTH with enhanced production of corticosterone, but not cortisol, which is
      produced constitutively. Organ-cultured human scalp hair follicles also show a
      fully functional HPA axis equivalent, including cortisol synthesis and secretion
      and negative feedback regulation by cortisol on CRH expression. Thus,
      differential, CRH-driven responses of defined cutaneous cell populations
      reproduce key features of the central HPA axis at the tissue/single cell levels.

PMID- 17197076
TI  - Tangeretin and nobiletin induce G1 cell cycle arrest but not apoptosis in human
      breast and colon cancer cells.
AB  - Tangeretin and nobiletin are citrus flavonoids that are among the most effective
      at inhibiting cancer cell growth in vitro and in vivo. The antiproliferative
      activity of tangeretin and nobiletin was investigated in human breast cancer cell
      lines MDA-MB-435 and MCF-7 and human colon cancer line HT-29. Both flavonoids
      inhibited proliferation in a dose- and time-dependent manner, and blocked cell
      cycle progression at G1 in all three cell lines. At concentrations that resulted
      in significant inhibition of proliferation and cell cycle arrest, neither
      flavonoid induced apoptosis or cell death in any of the tumor cell lines. To test
      the ability of arrested cells to recover, cells that were incubated with
      tangeretin and nobiletin for 4 days were then cultured in flavonoid-free medium
      for an additional 4 days. Cells resumed proliferation similar to untreated
      control within a day of flavonoid removal. Cell cycle distribution was similar to
      that of control within 4 days of flavonoid removal. These data indicate that, in
      these cell lines at concentrations that inhibit proliferation up to 80% over 4
      days, tangeretin and nobiletin are cytostatic and significantly suppress
      proliferation by cell cycle arrest without apoptosis. Such an agent could be
      expected to spare normal tissues from toxic side effects. Thus, tangeretin and
      nobiletin could be effective cytostatic anticancer agents. Inhibition of
      proliferation of human cancers without inducing cell death may be advantageous in
      treating tumors as it would restrict proliferation in a manner less likely to
      induce cytotoxicity and death in normal, non-tumor tissues.

PMID- 17197077
TI  - Removal of acid blue 062 on aqueous solution using calcinated colemanite ore
      waste.
AB  - Colemanite ore waste (CW) has been employed as adsorbent for the removal of acid
      blue 062 anionic dye (AB 062) from aqueous solution. The adsorption of AB 062
      onto CW was examined with respect to contact time, calcination temperature,
      particle size, pH, adsorbent dosage and temperature. The physical and chemical
      properties of the CW, such as particle sizes and calcinations temperature, play
      important roles in dye adsorption. The dye adsorption largely depends on the
      initial pH of the solution with maximum uptake occurring at pH 1. Three
      simplified kinetics models, namely, pseudo-first order, pseudo-second order, and
      intraparticle diffusion models were tested to investigate the adsorption
      mechanisms. The kinetic adsorption of AB 062 on CW follows a pseudo-second order
      equation. The adsorption data have been analyzed using Langmuir and Freundlich
      isotherms. The results indicate that the Langmuir model provides the best
      correlation of the experimental data. Isotherms have also been used to obtain the
      thermodynamic parameters such as free energy, enthalpy and entropy of the
      adsorption of dye onto CW.

PMID- 17197078
TI  - Biosorption and bioreduction of Cr(VI) by a microalgal isolate, Chlorella
      miniata.
AB  - The ability and mechanism of a microalgal isolate, Chlorella miniata to remove
      Cr(VI) were investigated. Kinetic studies indicated that both biosorption and
      bioreduction were involved in the Cr(VI) removal. The adsorbed Cr(VI) was reduced
      to Cr(III), and desorption studies indicated that Cr(III) occupied most of the
      adsorption sites on the biomass. The equilibrium time for Cr(VI) removal was
      dependent on various factors including initial pH, biomass and Cr(VI)
      concentrations. Equilibrium study showed that the Cr(VI) removal capacity was
      negatively related to the initial pH, and the biosorption capacity of total Cr
      [Cr(III) and Cr(VI)] reached the maximum at initial pH of 3.0. The spectrum of
      Fourier Transform Infrared Spectrometer analysis (FTIR) further confirmed that
      amino group on the algal biomass was the main adsorption site for Cr(VI)
      biosorption in acidic pH while the reduced Cr(III) was mainly sequestered by
      carboxylate group. The comparison between biosorption-bioreduction and direct
      bioreduction kinetic models proved that biosorption of Cr(VI) was the first step,
      followed by Cr(VI) bioreduction and Cr(III) biosorption on the algal biomass.

PMID- 17197079
TI  - Auditory cortical change detection in adults with Asperger syndrome.
AB  - The present study investigated whether auditory deficits reported in children
      with Asperger syndrome (AS) are also present in adulthood. To this end, event
      related potentials (ERPs) were recorded from adults with AS for duration, pitch,
      and phonetic changes in vowels, and for acoustically matched non-speech stimuli.
      These subjects had enhanced mismatch negativity (MMN) amplitudes particularly for
      pitch and duration deviants, indicating enhanced sound-discrimination abilities.
      Furthermore, as reflected by the P3a, their involuntary orienting was enhanced
      for changes in non-speech sounds, but tended to be deficient for changes in
      speech sounds. The results are consistent with those reported earlier in children
      with AS, except for the duration-MMN, which was diminished in children and
      enhanced in adults.

PMID- 17197080
TI  - p300 activation by Presenilin 1 but not by its M146L mutant.
AB  - The transcriptional co-activator p300 plays an important role in regulating gene
      expression in a number of different cell types. We have shown that wild type (WT)
      Presenilin 1 (PS1) stimulates the transcriptional activity ability of CREB
      Binding Protein (CBP), a close homolog of p300, whereas the Alzheimer's disease
      (AD) associated mutant of PS1 does not have this effect. A recent report has
      suggested that mutant PS1 can also disrupt the TCF/beta-catenin/CBP interaction
      but has no effect on the TCF/beta-catenin/p300 interaction. This suggests that
      the malregulation of CBP, but not of p300, caused by mutation in PS1 may be
      involved in the disease process. Here we show that wild type PS1 stimulates the
      transcriptional activity ability of p300 whereas an Alzheimer's disease
      associated mutant of PS1 did not produce this effect. To our knowledge, this is
      the first report that shows regulation of p300 activity by WT PS1 and not by
      mutant PS1, indicating that like CBP, p300 can be differentially regulated by WT
      PS1 compared to its AD-associated mutant.

PMID- 17197081
TI  - Delta opioids reduce the neurotransmitter release probability by enhancing
      transient (KV4) K+-currents in corticostriatal synapses as evaluated by the
      paired pulse protocol.
AB  - Field recordings were used to determine the influence of delta-opioid receptor
      activation on corticostriatal synaptic transmission. Application of the selective
      delta-opioid receptor agonist, [Tyr-D-Pen-Gly-Phe-D-Pen]-enkephalin (DPDPE, 1
      microM), decreased the amplitude of the field-excitatory synaptic potential and
      at the same time increased the paired pulse ratio (PPR) suggesting a presynaptic
      site of action. This response reversed rapidly when DPDPE was washed and blocked
      by 1 nM of the selective delta-receptor antagonist naltrindole. Neither omega
      conotoxin GVIA (1 microM) nor omega-agatoxin TK (400 nM), blockers of N- and P/Q
      type Ca2+-channels, respectively, nor TEA (1 mM), blocker of some classes of K+
      channels, occluded the effects of DPDPE. Instead, 1 mM 4-AP or 400 microM Ba2+
      occluded completely the effects of DPDPE. Therefore, the results suggest that the
      modulation by delta opioids at corticostriatal terminals is mediated by transient
      (KV4) K+-conductances.

PMID- 17197082
TI  - 'Prior entry' for pain: attention speeds the perceptual processing of painful
      stimuli.
AB  - We investigated whether the perception of simultaneity for pairs of nociceptive
      and visual stimuli was dependent upon the focus of participants' attention to a
      particular sensory modality (either pain or vision). Two stimuli (one painful and
      the other visual) were presented randomly at different stimulus onset
      asynchronies (SOAs) using the method of constant stimuli. Participants made
      unspeeded verbal responses as to which stimulus they perceived as having been
      presented first, or else responded that the two stimuli were presented
      simultaneously. This temporal discrimination task was repeated under three
      different attention conditions (blocks): divided attention, attend pain, and
      attend vision. The results showed that under conditions of divided attention,
      nociceptive stimuli had to be presented before visual stimuli in order for the
      two to be perceived as simultaneous. A comparison of the two focused attention
      conditions revealed that the painful stimulus was perceived as occurring earlier
      in time (relative to the visual stimulus) when attention was directed toward pain
      than when it was directed toward vision. These results provide the first
      empirical demonstration that attention can modulate the temporal perception of
      painful stimuli.

PMID- 17197084
TI  - The effects of interstimulus interval on sensory gating and on preattentive
      auditory memory in the oddball paradigm. Can magnitude of the sensory gating
      affect preattentive auditory comparison process?
AB  - P50, and mismatch negativity (MMN) are components of event-related potentials
      (ERP) reflecting sensory gating and preattentive auditory memory, respectively.
      Interstimulus interval (ISI) is an important determinant of the amplitudes of
      these components and N1. In the present study the interrelation between stimulus
      gating and preattentive auditory sensory memory were investigated as a function
      of ISI in 1.5, 2.5 and 3.5s in 15 healthy volunteered participants. ISI factor
      affected the N1 peak amplitude significantly. MMN amplitude in 2.5s ISI was
      significantly smaller compared to 1.5 and 3.5s ISI. ISI X stimuli interaction on
      P50 amplitude was statistically significant. P50 amplitudes to deviant stimuli in
      2.5s ISI were larger than the P50 amplitudes in other ISIs. P50 difference (P50d)
      waveform amplitude correlated significantly with MMN amplitude. The results
      suggest that: (i) auditory sensory gating could affect preattentive auditory
      sensory memory by supplying input to the comparator mechanism; (ii) 2.5s ISI is
      important in displaying the sensory gating and preattentive auditory sensory
      memory relation.

PMID- 17197083
TI  - Phenylephrine and pilocarpine eye drop test for dementia with Lewy bodies and
      Alzheimer's disease.
AB  - Pupillary response test using dilute phenylephrine, a sympathetic agonist, and
      dilute pilocarpine, a cholinergic agonist, were performed in 24 patients with
      dementia with Lewy bodies (DLB), 40 patients with Alzheimer's disease (AD), and
      23 normal elderly subjects. The mydriatic response to 0.5% phenylephrine was
      significantly greater in the DLB group than in the AD and control groups. The
      mydriatic change correlated inversely with the reduction in cardiac 123I
      metaiodobenzylguanidine uptake. In contrast, miotic response to 0.0625%
      pilocarpine was significantly greater in the DLB and AD groups than in the
      control group. The pupil assay using combined phenylephrine and pilocarpine eye
      drop test may be useful in the detection of patients with DLB and AD and in
      distinguishing between them.

PMID- 17197086
TI  - Differential expression of heat shock protein mRNAs under in vivo glutathione
      depletion in the mouse retina.
AB  - Heat shock proteins (HSPs) are highly conserved proteins playing a protective
      role under deleterious conditions caused by a wide variety of pathophysiological,
      including environmental stresses. Glutathione (GSH) is known to play a critical
      role in the cellular defense against unregulated oxidative stress in mammalian
      cells including neurons. We previously demonstrated that GSH depletion induced
      cell death in the retina, but the mechanism(s) of cellular protection were not
      clear. Unregulated oxidative stress was induced by depletion of intracellular GSH
      by systematic administration of buthionine sulphoximine (BSO), an inhibitor of
      gamma-glutamylcysteine synthetase. After 0, 1, 4 and 7 days of BSO
      administration, we examined expression of both large and small HSP mRNAs
      (hsp90alpha, hsp90beta, hsp70, hsp60 and hsp25) in oxidative-stressed mouse
      retina. Of large HSPs, only hsp70 expression was significantly decreased from 1
      day after BSO injection, whereas expression of other large hsps was not changed
      on day 1. Expression of hsp60 decreased on 4 days, whereas expression of hsp90
      decreased on 7 days after BSO administration. Different from large HSPs, a small
      HSP, hsp25 increased its expression to a great extent from 1 day after BSO
      administration. Taken together, our results show that unregulated oxidative
      stress could induce differential expression of HSPs, which, in turn, may play
      distinct roles in the cellular defense. Targeting HSPs, therefore, may provide
      novel tools for treatment of retinal degenerative diseases such as glaucoma,
      retinopathy or age-related macular degeneration.

PMID- 17197085
TI  - Major defects in neocortical GABAergic inhibitory circuits in mice lacking the
      fragile X mental retardation protein.
AB  - This study focused on the cytoarchitectonic and morphological differences in GABA
      releasing interneurons between adult Fmr1 knock-out (FMR1KO) and wild-type (WT)
      mice in the somatosensory cortex. Our results showed a robust reorganization of
      neocortical, but not hippocampal inhibitory circuits in the FMR1KO mouse. The
      reorganization is characterized by a significant reduction (20%, p<0.001) in the
      densities of parvalbumin (PV)-positive, but not calbindin (CB) and calretinin
      (CR)-positive interneurons. A significant enlargement of soma size and an altered
      lamina distribution of PV but not CR and CB cells was also observed.
      Additionally, there was a modest but significant increase in TrkB
      immunoreactivity in PV-positive cells in the FMR1KO mouse. These results provide
      the first report showing significant alterations of GABA-releasing interneurons
      in the mouse model of fragile X syndrome. Uncovering the changes in specific
      GABAergic inhibitory circuits could help understand mechanisms underlying the
      behavior deficits of fragile X syndrome and autism.

PMID- 17197087
TI  - 5-HT1A receptor activation counteracted the effect of acute immobilization of
      noradrenergic neurons in the rat locus coeruleus.
AB  - The aim of our study was to evaluate the effect of acute stress and the 5-HT(1A)
      receptor involvement in both, the hippocampus noradrenaline (NA) tissue levels
      and the c-Fos immunoreactivity (c-Fos-IR) in the catecholaminergic neurons of the
      locus coeruleus (LC). Double immunocytochemical staining of tyrosine hydroxilase
      (TH) and c-Fos protein combined with stereological techniques were used to study
      the specific cell activation in the LC neurons in five experimental groups
      (control group, immobilization (1h) group, 8-OH-DPAT group (8-OH-DPAT 0.3mg/kg,
      s.c.), DPAT+IMMO group (8-OH-DPAT 0.3mg/kg, s.c., 30' prior acute immobilization)
      and WAY+DPAT+IMMO group (WAY-100635 0.3mg/kg, s.c. and 8-OH-DPAT 0.3mg/kg, s.c.,
      45'and 30', respectively, before immobilization). The results showed that
      hippocampal NA tissue levels and c-Fos-IR in the TH positive neurons of the LC
      were significantly increased immediately and after 90', respectively, after the
      immobilization period. Pre-treatment with 8-OH-DPAT counteracted the effects
      induced by immobilization, but pre-treatment with WAY-100635 did not block the
      effects induced by 8-OH-DPAT. These results suggest that noradrenaline system is
      associated in a significant way with immobilization stress. The role of 5-HT(1A)
      receptor activation in this stress response is also discussed.

PMID- 17197089
TI  - BMD, fMRI study and brain hypoactivity.

PMID- 17197088
TI  - Trait anger expressiveness and pain-induced beta-endorphin release: support for
      the opioid dysfunction hypothesis.
AB  - The anger management styles of anger-in (inhibition) and anger-out (direct
      expression) are positively associated with pain responsiveness. Opioid blockade
      studies suggest that hyperalgesic effects of trait anger-out, but not those of
      trait anger-in, are mediated in part by opioid analgesic system dysfunction. The
      current study tested the opioid dysfunction hypothesis of anger-out using an
      alternative index of opioid function: pain-induced changes in plasma endogenous
      opioids. Plasma beta-endorphin (BE) was assessed at rest and again following
      exposure to three laboratory acute pain tasks (finger pressure, ischemic, and
      thermal) in 14 healthy controls and 13 chronic low back pain (LBP) subjects. As
      expected, acute pain ratings correlated positively with measures of anger-in
      (both groups) and anger-out (LBP group; p's<.05). Greater pain-induced increases
      in BE were associated with significantly lower pain ratings in both groups
      (p's<.05). Hierarchical multiple regression indicated that greater anger-out
      significantly predicted smaller pain-induced BE increases (p<.05). Subject type
      did not moderate this association (p>.10). Anger-in did not display significant
      main or interaction effects on pain-induced BE changes (p's>.10). The significant
      association between anger-out and BE release partially mediated the hyperalgesic
      effects of anger-out on pain unpleasantness, and was not attenuated by
      statistical control of general negative affect. This suggests unique associations
      with expressive anger regulation. Elevated trait anger-out therefore appears to
      be associated with opioid analgesic system dysfunction, whether it is indexed by
      responses to opioid blockade or by examining circulating endogenous opioid
      levels. Possible "statextrait" interactions on these anger-related opioid system
      differences are discussed.

PMID- 17197090
TI  - Nociceptive nerve activity in an experimental model of knee joint osteoarthritis
      of the guinea pig: effect of intra-articular hyaluronan application.
AB  - Nociceptive impulse activity was recorded extracellularly from single A delta and
      C primary afferents of the guinea pig's medial articular nerve after induction of
      an experimental osteoarthritis in the knee joint by partial medial menisectomy
      and transection of the anterior cruciate ligament (PMM+TACL). Also, the analgesic
      effects of intra-articular hyaluronan solutions were evaluated. Healthy, PMM+TACL
      operated, sham-operated (opening of the joint capsule without PMM and TACL
      surgery) and acutely inflamed (intra-articular kaolin-carrageenan, K-C) animals
      were used. The stimulus protocol consisted of torque meter-controlled,
      standardized innocuous and noxious inward and outward rotations of the joint.
      This stimulus protocol of 50 s duration was repeated every 5 min for 70 min. One
      day, one week and three weeks after PMM+TACL, the movement-evoked discharges of A
      delta articular afferents were increased significantly over values found in sham
      operated animals. The discharges of C fibers were significantly augmented only
      one week after PMM+TACL surgery. Filling of the joint cavity with a high
      viscosity hyaluronan solution (hylan G-F 20, Synvisc) immediately and three days
      after surgery reduced significantly the enhanced nerve activity observed in joint
      afferent fibers one day and one week after surgery. Augmentation of movement
      evoked discharges in K-C acutely inflamed knee joints was similar to that
      observed one week after PMM+TACL. Our results indicate that in the PMM+TACL model
      of osteoarthritis in guinea pigs, enhancement of nociceptive responses to joint
      movement was primarily associated to post-surgical inflammation. Intra-articular
      injection of an elastoviscous hyaluronan solution reduced the augmented nerve
      activity.

PMID- 17197092
TI  - Electron channelling based crystallography.
AB  - Electron channelling occurs when the incident electron beam is parallel to the
      atom columns of an object, such as a crystal or a particular crystal defect.
      Then, the electrons are trapped in the electrostatic potential of an atom column
      in which they scatter dynamically. This picture provides physical insight and
      explains why a one-to-one correspondence is maintained between the exit wave and
      the projected structure, even in case of strong dynamical scattering. Moreover,
      the theory is very useful to invert the dynamical scattering, that is, to derive
      the projected structure from the exit wave. Finally, it can be used to determine
      the composition of an atom column with single atom sensitivity or to explain
      dynamical electron diffraction effects. In this paper, an overview of the
      channelling theory will be given together with some recent applications.

PMID- 17197093
TI  - Characterization of a Cryptosporidium muris infection and reinfection in CF-1
      mice.
AB  - To establish control values for circulating cells and immune associated organs
      over the course of a self-limiting Cryptosporidium muris infection and
      rechallenge infection, mice were sacrificed at intervals starting before oral
      inoculation and ending after oocyst shedding had ceased. These values were used
      in other experiments to evaluate changes in these parameters induced by a single
      dose glucocorticoid immunosuppression model and in other immunosuppression
      studies. Flow cytometry counts of circulating T-lymphocytes and neutrophils,
      differential leukocyte counts, leukocyte morphology, spleen and thymus changes,
      and oocyst shedding were evaluated. Immediately after C. muris oocyst inoculation
      and up to the start of oocyst production (day 0 to day 7), the circulating blood
      profile showed a 50% drop in all leukocytes, including both large and small
      lymphocytes and CD3, CD4 and CD8 T-lymphocytes. There was an initial slight rise
      in circulating mature neutrophils after oocyst inoculation but numbers promptly
      dropped below normal and remaineded below normal. In the differential cell
      counts, monocytes with a fat, oval morphology increased by 60% at 24 h and
      remained high through oocyst shedding and beyond (day 8 through day 36). During
      oocyst shedding and continuing past the end of shedding, T-lymphocytes increased
      100%. Monocytes with a flat, angular morphology increased in a similar manner.
      Immediately after oocyst inoculation the spleen contracted by 29%, but became 92%
      larger than its pre-inoculation size by day 14 when heavy oocyst shedding began.
      It remained enlarged through the end of oocyst shedding (day 29) and beyond (day
      36). Spleen volume decreased and increased similar to changes in T-cell numbers.
      Throughout the C. muris infection the thymus remained largely unchanged. The
      transit of an oocyst bolus was followed from the stomach through the gut to the
      colon. No oocysts could be found in the stomach, caecum or feces of mice one half
      hour after oocyst inoculation. Likewise, an oral bolus of India ink passed from
      the stomach entirely into the colon after 3 h; therefore, no oocysts from the
      inoculum passed completely through the intestine and out into the feces.
      Recovered mice rechallenged with C. muris showed increased B-lymphocyte numbers;
      however, T-lymphocyte numbers remained level. The large lymphocytes increased
      after rechallenge, peaking on day 3, then decreased through day 10. B-cell
      numbers followed a pattern similar to the large lymphocytes. On day 10 of
      infection monocytes with a fat oval morphology rose sharply while B-cells fell in
      number. In both the initial infection and the rechallenge there was no unique
      blood profile which could definitely indicate a protozoal disease or identify a
      specific point during the course of the disease. There was no increase in the
      number of either small or large lymphocytes prior to increases in fat or flat
      monocytes.

PMID- 17197095
TI  - Focal adhesion kinase determines the fate of death or survival of cells in
      response to TNFalpha in the presence of actinomycin D.
AB  - We speculated that focal adhesion kinase (FAK) might play a critical role in the
      TNFalpha-induced cell death. In this study, we found that FAK-/- cells are more
      sensitive to TNFalpha-induced apoptosis in the presence of actinomycin D (Act D)
      compared to FAK+/- cells. Prosurvival pathways are activated by the rapid
      recruitment of complex I, comprising TNFR1, TRADD, RIP and TRAF2, which leads to
      the activation of the NF-kappaB pathway. On the other hand, proapoptotic pathways
      are activated by complex II, the death-inducing signaling complex (DISC), which
      contains TNFR1, TRADD, RIP, and FADD, and procaspase-8 proteins. As TNFR1, TRADD,
      and RIP are included in both Complex I and DISC, we speculated that RIP might be
      a key protein. Coimmunoprecipitation assays revealed that RIP is included in
      complex I in FAK+/- cells, and FAK was associated with RIP. On the other hand,
      RIP is included in DISC in FAK-/- cells. FAK might be a key protein in the
      formation of complex I and the activation of NF-kappaB. Furthermore, Akt was
      activated in FAK+/- cells, but not FAK-/- cells. In conclusion, we first
      demonstrated that FAK determines the pathway leading to death or survival in
      TNFalpha/ActD-stimulated fibroblasts.

PMID- 17197096
TI  - Complex oligosaccharides are N-linked to Kv3 voltage-gated K+ channels in rat
      brain.
AB  - Neuronal Kv3 voltage-gated K(+) channels have two absolutely conserved N
      glycosylation sites. Here, it is shown that Kv3.1, 3.3, and 3.4 channels are N
      glycosylated in rat brain. Digestion of total brain membranes with peptide N
      glycosidase F (PNGase F) produced faster migrating immunobands than those of
      undigested membranes. Additionally, partial PNGase F digests showed that both
      sites are occupied by oligosaccharides. Neuraminidase treatment produced a
      smaller immunoband shift relative to PNGase F treatment. These results indicate
      that both sites are highly available and occupied by N-linked oligosaccharides
      for Kv3.1, 3.3, and 3.4 in rat brain, and furthermore that at least one
      oligosaccharide is of complex type. Additionally, these results point to an
      extracytoplasmic S1-S2 linker in Kv3 proteins expressed in native membranes. We
      suggest that N-glycosylation processing of Kv3 channels is critical for the
      expression of K(+) currents at the surface of neurons, and perhaps contributes to
      the pathophysiology of congenital disorders of glycosylation.

PMID- 17197094
TI  - Glutamine, insulin and glucocorticoids regulate glutamine synthetase expression
      in C2C12 myotubes, Hep G2 hepatoma cells and 3T3 L1 adipocytes.
AB  - The cell-specific regulation of glutamine synthetase expression was studied in
      three cell lines. In C2C12 myotubes, glucocorticoids increased the abundance of
      both glutamine synthetase protein and mRNA. Culture in the absence of glutamine
      also resulted in very high glutamine synthetase protein abundance but mRNA levels
      were unchanged. Glucocorticoids also increased the abundance of glutamine
      synthetase mRNA in Hep G2 hepatoma cells but this was not reflected in changes in
      protein abundance. Culture of Hep G2 cells without glutamine resulted in very
      high levels of protein, again with no change in mRNA abundance. Insulin was
      without effect in both C2C12 and Hep G2 cells. In 3T3 L1 adipocytes
      glucocorticoids increased the abundance of both glutamine synthetase mRNA and
      protein, insulin added alone had no effect but in the presence of glucocorticoids
      resulted in lower mRNA levels than seen with glucocorticoids alone, although
      protein levels remained high under such conditions. In contrast to the other cell
      lines glutamine synthetase protein levels were relatively unchanged by culture in
      the absence of glutamine. The results support the hypothesis that in myocytes,
      and hepatomas, but not in adipocytes, glutamine acts to moderate glutamine
      synthetase induction by glucocorticoids.

PMID- 17197097
TI  - Class A plexin expression in axotomized rubrospinal and facial motoneurons.
AB  - The semaphorin family of guidance molecules plays a role in many aspects of
      neural development, and more recently semaphorins have been implicated to
      contribute to the failure of injured CNS neurons to regenerate. While semaphorin
      expression patterns after neural injury are partially understood, little is known
      about the expression of their signal transducing transmembrane receptors, the
      plexins. Therefore, in this study, we compared the expression patterns of all
      class A plexins (Plxn-A1, A2, A3, A4) in mouse CNS (rubrospinal) and peripheral
      nervous system (PNS)-projecting (facial) motoneurons for up to two weeks
      following axonal injury. Using in situ hybridization, immunohistochemistry, and
      Western blot analysis, in rubrospinal neurons, Plxn-A1 mRNA and protein and Plxn
      A4 expression did not change as a result of injury while Plxn-A2 mRNA increased
      and Plxn-A3 mRNA was undetectable. In facial motoneurons, Plxn-A1, -A3 and -A4
      mRNA expression increased, Plxn-A2 mRNA decreased while Plxn-A1 protein
      expression did not change following injury. We demonstrate that with the
      exception of the absence of Plxn-A3 mRNA in rubrospinal neurons, both injured
      rubrospinal (CNS) and facial (PNS) neurons maintain expression of all plexin A
      family members tested. Hence, there are distinct expression patterns of the
      individual plexin-A family members suggesting that regenerating rubrospinal and
      facial motoneurons have a differential ability to transduce semaphorin signals.

PMID- 17197098
TI  - Predominant surface distribution of neurokinin-3 receptors in non-dopaminergic
      dendrites in the rat substantia nigra and ventral tegmental area.
AB  - Neurokinin-3 (NK(3)) receptors are prevalent within the substantia nigra (SN) and
      ventral tegmental area (VTA), where their activation can affect motor and
      motivational behaviors as well as cardiovascular function and stress responses.
      These actions are mediated, in part, by dopaminergic neurons in each region. To
      determine the relevant sites for activation of these receptors, we examined the
      electron microscopic localization of NK(3) receptors and tyrosine hydroxylase
      (TH), the catecholamine synthesizing enzyme in dopaminergic neurons in the SN and
      VTA of rat brain. In each region, immunogold-silver labeling for NK(3) receptors
      was detected in many somatodendritic profiles, some of which contained TH
      immunoreactivity. NK(3)-immunogold particles were largely associated with
      endomembranes resembling smooth endoplasmic reticulum, and only occasionally
      located on the plasma membrane in TH-labeled dendrites. In comparison with these
      dendrites, non-TH immunoreactive dendrites contained significantly more total
      (VTA) and more plasmalemmal (VTA and SN) NK(3)-immunogold particles. In each
      region, NK(3) gold particles also were seen in axonal as well as glial profiles,
      some of which contacted TH-immunoreactive dendrites. The NK(3)-labeled axon
      terminals formed either symmetric or asymmetric, excitatory-type synapses, the
      latter of which were significantly more prevalent in the VTA, compared with SN.
      These results provide the first ultrastructural evidence indicating that NK(3)
      receptors are available in cytoplasmic reserve in dopaminergic neurons, but more
      immediately accessible at the plasmalemmal surface of non-dopaminergic dendrites
      in both the SN and VTA. The activation of these receptors, together with the
      NK(3) receptors in either the presynaptic axon terminals or glia may contribute
      to the diverse physiological effects of tachykinins in each region, and most
      prominently involving excitatory inputs to the VTA.

PMID- 17197099
TI  - Endomorphin 1 activates nitric oxide synthase 2 activity and downregulates nitric
      oxide synthase 2 mRNA expression.
AB  - Endomorphins 1 and 2 are newly discovered opioid tetrapeptides whose structure is
      more resistant to enzymatic degradation than that of other opioid peptides.
      Endomorphins 1 and 2 are considered as endogenous ligands with a high affinity
      for mu receptors. A number of studies have shown that opioid peptides per se can
      induce release of nitric oxide from rodent and human immune cells. Endomorphins
      seemed to be involved in the process of vasodilatation by stimulating release of
      nitric oxide. In our study we stimulated in vitro J774 macrophages with different
      concentrations of endomorphin 1 or 2 for measuring nitric oxide release and
      nitric oxide synthase 2 (NOS 2) mRNA expression. Results showed that 48 h
      incubation did not enhance nitric oxide release when measured with the Griess
      method. On the other hand, using real-time amperometric detection of nitric oxide
      release shortly after challenge with endomorphins, we showed that only 10(-6) M
      endomorphin 1 was able to stimulate nitric oxide release from a J774 macrophage
      cell line by activation of NOS 2 isoenzyme. The peak release was 1000-1500 s
      after stimulation and was in the range of nitric oxide release stimulated with 10
      microg/ml lipopolysaccharide. In contrast to this, endomorphin 2 failed to induce
      nitric oxide release in all tested concentrations. Using a specific inhibitor of
      nitric oxide synthase 2 (N-(3-[aminomethyl]benzyl)acetamidine, 1400W) we
      eliminated the stimulatory effect of endomorphin 1 on nitric oxide release. The
      expression of mRNA for NOS 2 in J774 macrophages, after 30 min incubation with
      either lipopolysaccharide or 10(-6) M endomorphin 1 was not upregulated. As
      expected, lipopolysaccharide induced de novo NOS 2 transcription within 4 h. At
      the same time, in contrast to lipopolysaccharide, mRNA expression of cells
      treated with endomorphin 1 was downregulated. Since a mu-opioid receptor specific
      antagonist beta-funaltrexamine hydrochloride inhibited nitric oxide release from
      endomorphin 1-treated cells, the effect seemed to be mu-opioid receptor mediated.

PMID- 17197100
TI  - Expression of fibroblast growth factor-2 and brain-derived neurotrophic factor
      mRNA in the medial prefrontal cortex and hippocampus after uncontrollable or
      controllable stress.
AB  - Neurotrophic factors, including basic fibroblast growth factor (FGF-2) and brain
      derived neurotrophic factor (BDNF) are known to be affected by exposure to
      stressful experiences. Here, we examine the effects of behaviorally controllable
      (escapable tailshock, ES) or uncontrollable (inescapable tailshock, IS) stress on
      the expression of FGF-2 and BDNF mRNA in subregions of the medial prefrontal
      cortex (mPFC) and the hippocampal formation (HF) of male Sprague-Dawley rats. ES
      rats were placed in Plexiglas boxes equipped with a free spinning wheel and IS
      rats were placed in identical boxes with the wheels fixed. ES and IS rats were
      yoked such that they received the same tailshocks, but the ES rat could terminate
      each shock for both rats. No stress controls (NS) remained in their home cages.
      Rats were killed 0, 2, 24, or 72 h after termination of the stress session. In
      situ hybridization was performed to measure FGF-2 and BDNF mRNA in the mPFC and
      HF. In the mPFC, ES produced a significant increase in FGF-2 mRNA expression at 0
      and 2 h post-stress. In the HF, ES produced a greater increase in FGF-2 mRNA
      expression than IS and NS only in CA2. ES also produced an increase in BDNF mRNA
      expression in the anterior cingulate at 0 h post-stress. No effects of stressor
      controllability on BDNF were observed in the HF, although both ES and IS
      decreased BDNF mRNA in the DG. FGF-2 in the mPFC may be involved in emotional
      regulation ("coping") during stressful experiences.

PMID- 17197103
TI  - Spatial organization and dynamic properties of neurotransmitter release sites in
      the enteric nervous system.
AB  - Synaptic communication requires an efficient coupling of vesicle fusion to
      release neurotransmitter and vesicle retrieval to repopulate the synapse. In
      synapses of the CNS many proteins involved in exocytosis, endocytosis and
      refilling of vesicles have been identified. However, little is known about the
      organization and functioning of synaptic contacts in the enteric nervous system
      (ENS). We used fluorescent antibodies against presynaptic proteins
      (synaptobrevin, synaptophysin, synaptotagmin and bassoon) to identify synaptic
      contacts not only in guinea-pig enteric ganglia but also in the interconnecting
      fiber strands. Staining patterns were not altered by colchicine (100 microM),
      ruling out a contribution of protein transport at the time of fixation. Active
      release sites at fiber intersections and around neuronal cell bodies were labeled
      with FM1-43 (10 microM) by high K+ or electric field stimulation (EFS). During a
      second round of EFS, vesicles were reused, as reflected by dye loss. Destaining
      rates increased with stimulus frequency (2-30 Hz), reaching a maximum at about 15
      Hz, likely caused by synaptic depression at higher frequencies. Tetrodotoxin
      (TTX, 1 microM) as well as nominally zero external Ca2+ (2 mM EGTA) prevented all
      destaining. The readily releasable pool (RRP, a subset of vesicles docked at the
      membrane and ready to fuse upon [Ca2+]i increase) can be specifically released by
      a hypertonic challenge (500 mM sucrose). We measured this pool to be
      approximately 27% of the total recycling pool, remarkably similar to synapses in
      the CNS. In whole-mount preparations, FM1-43 also reliably labeled active release
      sites in ganglia, fiber strands and in muscle bundles. The staining pattern
      indicated that the presynaptic antibodies mainly labeled active sites. The
      presence of numerous release sites suggests information processing capability
      within interconnecting fibers. With FM imaging, enteric synaptic function can be
      monitored independent of any postsynaptic modulation. Although electron
      microscopy data suggest that ENS synapses may not be as specialized as
      hippocampal synapses, remarkably similar release properties were measured.

PMID- 17197102
TI  - Role of the anterior cingulate and medial orbitofrontal cortex in processing drug
      cues in cocaine addiction.
AB  - Our goal in the current report was to design a new functional magnetic resonance
      imaging (fMRI) task to probe the role of the anterior cingulate cortex (ACC) and
      orbitofrontal cortex (OFC) in processing of salient symptom-related cues during
      the simultaneous performance of an unrelated task in drug-addicted persons. We
      used a novel fMRI color-word drug Stroop task in 14 individuals with cocaine use
      disorders; subjects had to press for color of drug vs. matched neutral words.
      Although there were no accuracy or speed differences between the drug and neutral
      conditions in the current sample of subjects, drug words were more negatively
      valenced than the matched neutral words. Further, consistent with prior reports
      in individuals with other psychopathologies using different Stroop fMRI
      paradigms, our more classical color-word Stroop design revealed bilateral
      activations in the caudal-dorsal anterior cingulate cortex (cdACC) and
      hypoactivations in the rostro-ventral anterior cingulate cortex/medial
      orbitofrontal cortex (rACC/mOFC). A trend for larger rACC/mOFC hypoactivations to
      the drug than neutral words did not survive whole-brain corrections.
      Nevertheless, correlation analyses indicated that (1) the more the cdACC drug
      related activation, the more negative the valence attributed to the drug words
      (r=-0.86, P<0.0001) but not neutral words; and (2) the more the rACC/mOFC
      hypoactivation to drug minus neutral words, the more the errors committed
      specifically to the drug minus neutral words (r=0.85, P<0.0001). Taken together,
      results suggest that this newly developed drug Stroop fMRI task may be a
      sensitive biobehavioral assay of the functions recruited for the regulation of
      responses to salient symptom-related stimuli in drug-addicted individuals.

PMID- 17197101
TI  - Developmental regulation of nicotinic acetylcholine receptors within midbrain
      dopamine neurons.
AB  - We have combined anatomical and functional methodologies to provide a
      comprehensive analysis of the properties of nicotinic acetylcholine receptors
      (nAChRs) on developing dopamine (DA) neurons of Sprague-Dawley rats. Double
      labeling in situ hybridization was used to examine the expression of nAChR
      subunit mRNAs within developing midbrain DA neurons. As brain maturation
      progressed there was a change in the pattern of subunit mRNA expression within DA
      neurons, such that alpha3 and alpha4 subunits declined and alpha6 mRNA increased.
      Although there were strong similarities in subunit mRNA expression in substantia
      nigra (SNc) and ventral tegmental area (VTA), there was higher expression of
      alpha4 mRNA in SNc than VTA at gestational day (G) 15, and of alpha5, alpha6 and
      beta3 mRNAs during postnatal development. Using a superfusion neurotransmitter
      release paradigm to functionally characterize nicotine-stimulated release of
      [(3)H]DA from striatal slices, the properties of the nAChRs on DA terminals were
      also found to change with age. Functional nAChRs were detected on striatal
      terminals at G18. There was a decrease in maximal release in the first postnatal
      week, followed by an increase in nicotine efficacy and potency during the second
      and third postnatal weeks. In the transition from adolescence (postnatal days (P)
      30 and 40) to adulthood, there was a complex pattern of functional maturation of
      nAChRs in ventral, but not dorsal, striatum. In males, but not females, there
      were significant changes in both nicotine potency and efficacy during this
      developmental period. These findings suggest that nAChRs may play critical
      functional roles throughout DA neuronal maturation.

PMID- 17197104
TI  - Different metabolism of glutamatergic and GABAergic compartments in superfused
      hippocampal slices characterized by nuclear magnetic resonance spectroscopy.
AB  - We investigated intermediary metabolism using (13)C-glucose and (13)C-acetate
      tracers followed by (13)C-nuclear magnetic resonance (NMR) isotopomer analysis in
      rat hippocampal slice preparations, the most widely used preparation for
      electrophysiological studies. Slices displayed a stable metabolic activity over a
      wide range of superfusion periods in the absence or presence of 50 muM 4
      aminopyridine (4AP), which triggers an intermittent burst-like neuronal firing.
      This caused an increase of tricarboxylic acid (TCA)-related amino acids
      (glutamate, aspartate and GABA) and shortened the time required to reach
      metabolic and isotopic steady state (3 h in the presence of 4AP and 7 h in its
      absence). (13)C-NMR isotopomer analysis revealed an increase in TCA flux in
      astrocytes and in GABA compartments greater than in putative glutamatergic
      neurons and the fitting of these data further indicated that the metabolic
      network in GABAergic and glutamatergic compartments has a different design and
      reacts differently to the stimulation by the presence of 4AP. These results show
      that (13)C-isotopomer analysis allows estimating metabolic parameters/fluxes
      under both steady- and non-steady-state metabolic conditions in hippocampal
      slices, opening the possibility of combining electrophysiological and metabolic
      studies in the same preparation.

PMID- 17197107
TI  - Culturally specific adaptation of a prevention intervention: an international
      collaborative research project.
AB  - This study adapted a U.S. drug use prevention program for use with Russian at
      risk adolescents, and explored directions for further development of programs
      addressing prevention of substance abuse and other health risk behaviors
      including risk of HIV infection. The adaptation process was conducted in phases,
      initially carried out in Seattle with 23 bilingual (English-Russian) youth and
      then further adapted in two Moscow schools with 44 "typical" youth. In the final
      phase, program adaptation for the Russian at-risk adolescents was achieved by
      conducting a pilot test of the adapted program lessons with Moscow at-risk
      adolescents (n=10), who met criteria of poor school performance and/or truancy.
      Observations and experience were used throughout to adapt and refine the program
      for at-risk youth. Modifications were made to represent more accurately
      colloquial Russian and to capture teen experiences common to Russian culture.
      Both U.S. and Russian youth characterized the lessons as engaging and valuable.
      They also expressed a need to learn about sexuality, drug use, and health; peer
      and romantic relationships; and problem-solving strategies.

PMID- 17197106
TI  - Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and
      AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass
      index, severity and age of onset.
AB  - Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade
      and is strongly familial with genetic factors. Ghrelin is an upstream regulator
      of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to
      leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in
      feeding and body weight. Obestatin which counteracts ghrelin action on feeding is
      derived from the same propeptide than ghrelin. BDNF has been involved in body
      weight regulation and its Val66Met polymorphism associated with AN. We therefore
      re-investigated the association between AN and the Leu72Met and Gln90Leu
      polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of
      AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes
      (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of
      these 4 single nucleotide polymorphisms were performed in 114 probands with AN
      and both their parents recruited in two specialized French centres. A
      transmission disequilibrium was observed for the Leu72Met SNP of the
      preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by
      clinical subtype, these two polymorphisms were preferentially transmitted for the
      trios with a bingeing/purging proband. An excess of transmission of the
      Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed.
      These results do not provide evidence for a preferential transmission of the
      66Met allele of BDNF but support the hypothesis that ghrelin and AGRP
      polymorphisms confers susceptibility to AN. Further simultaneous analysis of
      genetic variants of the biological determinants of energy metabolism and feeding
      behaviour in very large populations should contribute to the understanding of the
      high degree of heritability of eating disorders and to the description of
      pathophysiological patterns leading to life-threatening conditions in a highly
      redundant system.

PMID- 17197108
TI  - Is the seasonal variation in cancer prognosis caused by sun-induced folate
      degradation?
AB  - Recently, we have documented that the season of diagnosis affects the prognosis
      of Hodgkin's lymphoma, colon-, breast- and prostate-cancer patients in Norway.
      The relative risk of death was lower for the patients diagnosed during summer and
      autumn when compared with the winter diagnosis. We here hypothesise that UV
      (ultraviolet) induced degradation of folate may be the reason for the observed
      seasonal variations in cancer prognosis. It is known that folic acid, a synthetic
      form of folate, is degraded by UV radiation. We have also found that the most
      common folate derivative in the human body, 5-methyltetrahydrofolate, is UV
      sensitive.

PMID- 17197109
TI  - Early cry and later beautiful smile: "sonobiotic facilitation" hypothesis of
      odontogenesis.

PMID- 17197110
TI  - Autologous bone marrow transplantation/mobilization: a potential regenerative
      medicine for systemic degenerative disorders and healthy living.
AB  - Increased longevity is compromised for the quality of life due to prevalence of
      metabolic derangements and systemic degenerative disorders, as a result of
      lifestyle changes in modern days. In a craze to improve upon quality of life, use
      of pharmacological formulations aimed towards symptomatic treatment regimen is
      mandatory to manage variety of prevailing human ailments. However; these
      medicines have their own limitations and side effects, soliciting alternative
      therapy for better living. In light of preclinical and clinical studies on adult
      stem cells, bone marrow transplantation in healthy elderly individuals is likely
      to promote rejuvenation and prevent onset of degenerative disorders as well as
      cure prevailing disorders if any. Progress in unraveling pleuripotency of adult
      bone marrow stem cells compelled us to hypothesize that the only way to regain
      lost cells is to replace them with cells following the principle of 'Like begets
      Like' which may be achieved by autologous bone marrow
      transplantation/mobilization.

PMID- 17197105
TI  - Further characterization of a rat model of varicella zoster virus-associated
      pain: Relationship between mechanical hypersensitivity and anxiety-related
      behavior, and the influence of analgesic drugs.
AB  - Persistent herpes zoster-associated pain is a significant clinical problem and an
      area of largely unmet therapeutic need. Progress in elucidating the underlying
      pathophysiology of zoster-associated pain and related co-morbidity behavior, in
      addition to appropriately targeted drug development has been hindered by the lack
      of an appropriate animal model. This study further characterizes a recently
      developed rat model of zoster-associated hypersensitivity and investigates (a)
      response to different viral strains; (b) relationship between viral inoculum
      concentration ('dose') and mechanical hypersensitivity ('response'); (c)
      attenuation of virus-associated mechanical hypersensitivity by clinically useful
      analgesic drugs; and (d) measurement of pain co-morbidity (anxiety-like behavior)
      and pharmacological intervention in the open field paradigm (in parallel with
      models of traumatic peripheral nerve injury). Varicella zoster virus was
      propagated on fibroblast cells before s.c. injection into the glabrous footpad of
      the left hind limb of adult male Wistar rats. Control animals received injection
      of uninfected fibroblast cells. Hind-limb reflex withdrawal thresholds to
      mechanical, noxious thermal and cooling stimuli were recorded at specified
      intervals post-infection. Infection with all viral strains was associated with a
      dose-dependent mechanical hypersensitivity but not a thermal or cool
      hypersensitivity. Systemic treatment with i.p. morphine (2.5 mg/kg),
      amitriptyline (10 mg/kg), gabapentin (30 mg/kg), (S)-(+)-ibuprofen (20 mg/kg) and
      the cannabinoid WIN55,212-2 (2 mg/kg) but not the antiviral, acyclovir (50
      mg/kg), was associated with a reversal of mechanical paw withdrawal thresholds.
      In the open field paradigm, virus-infected and nerve-injured animals demonstrated
      an anxiety-like pattern of ambulation (reduced entry into the central area of the
      open arena) which was positively correlated with mechanical hypersensitivity.
      This may reflect pain-related co-morbidity. Further, anxiety-like behavior was
      attenuated by acute i.p. administration of gabapentin (30 mg/kg) in nerve
      injured, but not virus-infected animals. This model will prove useful in
      elucidating the pathophysiology of zoster-associated pain and provide a tool for
      pre-clinical screening of analgesic drugs.

PMID- 17197112
TI  - The potential for induction of autoimmune disease by a randomly-mutated self
      antigen.
AB  - The pathology of most autoimmune diseases is well described. However, the exact
      event that triggers the onset of the inflammatory cascade leading to disease is
      less certain and most autoimmune diseases are complex idiopathic diseases with no
      single gene known to be causative. In many cases, a relation to an infectious
      disease is described, and it is thought that microbes can play a direct role in
      induction of autoimmunity, for instance by molecular mimicry or bystander
      activation of autoreactive T cells. In contrast, less attention has been given to
      the possibility that modified self-antigens can be immunogenic and lead to
      autoimmunity against wildtype self-antigens. In theory, modified self-antigens
      can arise by random errors and mutations during protein synthesis and would be
      recognized as foreign antigens by naive B and T lymphocytes. Here, it is
      postulated that the initial auto-antigen is not a germline self-antigen, but
      rather a mutated self-antigen. This mutated self-antigen might interfere with
      peripheral tolerance if presented to the immune system during an infection. The
      infection lead to bystander activation of naive T and B cells with specificity
      for mutated self-antigen and this can lead to epitopespreading in which T and B
      cells with specificity for wildtype self-antigens are activated as a result of
      general inflammation.

PMID- 17197113
TI  - The rationale for activated protein C treatment in perinatal white matter injury.

PMID- 17197114
TI  - Marfan syndrome and liability to psychosis.

PMID- 17197111
TI  - The pattern of melatonin receptor expression in the brain may influence
      antidepressant treatment.
AB  - The pineal hormone melatonin produces most of its biological effects via G
      protein-coupled receptors MT1 and MT2. In mammals, these receptors are expressed
      in various tissues and organs including in the brain. Recent research points to a
      putative role of MT1/MT2 dimerization as a mechanism that could determine the
      receptor-mediated biological effects of melatonin. Brain content and the ratios
      between MT1 and MT2 receptors are affected by illness, e.g., Alzheimer's disease,
      and by prolonged drug treatment, e.g., antidepressants. New drugs with
      antidepressant properties that bind and activate melatonin receptors have been
      discovered. We hypothesize that endogenous, i.e., low, levels of melatonin could
      contribute to antidepressant effects depending on the expression pattern of
      melatonin receptors in the brain. Hence, we propose that a prolonged treatment
      with classical antidepressant drugs alters the brain ratio of MT1/MT2 receptors
      to enable the endogenous melatonin, which is secreted during the night, to
      further improve the antidepressant effects. A corollary of this hypothesis is
      that antidepressants would be less effective in conditions of pathologically
      altered brain melatonin receptors, e.g., in Alzheimer's patients or due to
      genetic polymorphisms. If our hypothesis is confirmed, supplementing classical
      antidepressant treatment with an appropriate dose of a melatonin receptor agonist
      might be used to improve antidepressant effects in subjects with a susceptible
      pattern of brain melatonin receptor expression.

PMID- 17197115
TI  - Lyme borreliosis and multiple sclerosis are associated with primary effusion
      lymphoma.
AB  - Multiple sclerosis (MS) is a chronic disease of the central nervous system
      characterized by chronic inflammation and demyelination. Studies suggested that
      the viral, especially Epstein-Barr virus infection, and bacterial infections,
      especially Borrelia burgdorferi infection, play a role in etiology of MS. MS
      prevalence parallels the distribution of the Lyme disease pathogen B.
      burgdorferi. Criteria used for diagnosis of MS can also be fulfilled in other
      conditions such as Lyme disease, a multisystem disorder resulting from infection
      by the tick-borne spirochete, B. burgdorferi. In the late period of Lyme disease
      demyelinating involvement of central nervous system can develop and MS can be
      erroneously diagnosed. A Lyme borreliosis can mimick central nervous system
      lymphoma. Also, B. burgdorferi has been implicated not only in etiology of MS,
      but also in etiology of lymphoma. Studies suggested that there is an increased
      risk of non-Hodgkin lymphoma in patients, who had a history of autoimmune
      diseases such as MS and that both non-Hodgkin's lymphomas and Hodgkin's disease
      were associated with Epstein-Barr virus infection. A small group of lymphomas
      called primary effusion lymphomas (PEL) is a recently individualized form of non
      Hodgkin's lymphoma (WHO classification) that exhibit exclusive or dominant
      involvement of serous cavities, without a detectable solid tumor mass. These
      lymphomas have also been linked to Epstein-Barr virus and human herpes virus type
      8 infections but virus negative cases have been described. Therefore, we propose
      that MS and neuroborreliosis are linked to central nervous system primary
      effusion lymphomas. As a first step in confirming or refuting our hypotheses, we
      suggest a thorough study of CSF in the patients suspected for the diagnosis of MS
      and Lyme borreliosis.

PMID- 17197117
TI  - Granular cell astrocytoma.
AB  - Granular cell astrocytoma (GCA) is a rare morphologic variant of astrocytomas,
      characterized by a prominent component of plump granular tumor cells. It has an
      aggressive clinical course as compared with conventional astrocytoma of the same
      grade. As its cytologic feature resembles that of a foamy histiocyte and,
      histologically, the tumor is rich in arborizing capillaries, it can be difficult
      to distinguish GCA from non-neoplastic diseases such as infarct or demyelinating
      disease. In this paper, a case of a GCA in a 28-year-old full-term pregnant woman
      suffering from a sudden episode of seizure during delivery is described, focusing
      on histopathological, immunohistochemical, and ultrastructural features.
      Histopathology and immunohistochemical phenotype of this tumor were identical to
      the previous reports. Ultrastructurally, secondary lysosome (so-called lipofuscin
      bodies) granules were present but not numerous; instead, many mitochondria and
      unusual paracrystalline inclusions were found in each tumor cell. In our case,
      the light microscopic granular appearance might be produced not only by
      phagolysomes but also by numerous mitochondria and paracrystalline inclusions.

PMID- 17197116
TI  - Mesenchymal stem/stromal cells (MSC) transfected with stromal derived factor 1
      (SDF-1) for therapeutic neovascularization: enhancement of cell recruitment and
      entrapment.
AB  - Recruited bone marrow-derived circulating cells (RBCCs) play a key role in
      therapeutic neovascularization. Several important steps take place during this
      process, which include mobilization, migration, recruitment, adhesion and
      invasion, entrapment, differentiation, as well as paracrine functions. Recent
      study indicated that recruitment and entrapment of RBCCs are vital steps in
      vascular endothelial growth factor (VEGF)-induced angiogenesis. This entrapment
      is modulated by another important chemokine: stromal derived factor 1 (SDF-1). We
      reason that the enhancement of entrapment might be a novel target for therapeutic
      neovascularization. Therefore we hypothesize that mesenchymal stem/stromal cells
      that secrete VEGF in situ could be transfected with SDF-1 (MSC(SDF-1)). Their
      combination could augment mobilization, recruitment, survival, and above all the
      entrapment of RBCCs, all of which might greatly augment the angiogenesis pathway.
      For these reasons, we further hypothesize that MSC(SDF-1) might become a next
      generation cell/chemokine therapy for therapeutic neovascularization.

PMID- 17197118
TI  - Estrogen sulfotransferase expression in endometrial stromal sarcomas: an
      immunohistochemical study.
AB  - Levels and activity of the enzyme estrogen sulfotransferase (EST) have been
      reported to play an important role in the regulation of in situ estrogen levels
      in human breast, prostate, and endometrial cancer. To better understand growth
      progression in endometrial stromal sarcomas (ESS), estrogen-dependent tumors, we
      analyzed the expression of EST in a series of 29 ESS. Archival formalin-fixed,
      paraffin-embedded material was analyzed immunohistochemically with a monoclonal
      antibody to EST using the peroxidase-antiperoxidase method. A score was
      calculated based on the percentage of positive tumor cells and staining
      intensity. EST staining was identified in 5 of 29 (18%) ESS and was scored as
      weakly positive, while 24 of 29 (82%) ESS were negative for EST. We demonstrate
      that a subset of ESS express EST, which may allow them to inactivate intratumoral
      estrogens. ESS without EST expression may have increased levels of biologically
      active estrogen, which explains the tumor progression of this entity and these
      patients may be at increased risk for recurrences and metastases.

PMID- 17197119
TI  - Feasibility of high-dose-rate brachytherapy salvage for local prostate cancer
      recurrence after radiotherapy: the University of California-San Francisco
      experience.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility and safety of
      salvage high-dose-rate (HDR) brachytherapy for locally recurrent prostate cancer
      after external beam radiotherapy (EBRT). METHODS AND MATERIALS: We
      retrospectively analyzed 21 consecutively accrued patients undergoing salvage HDR
      brachytherapy for locally recurrent prostate cancer after EBRT between November
      1998 and December 2005. After pathologic confirmation of locally recurrent
      disease, all patients were treated with 36 Gy in six fractions using two
      transrectal ultrasound-guided HDR prostate implants, separated by 1 week. Eleven
      patients received neoadjuvant hormonal therapy immediately presalvage, whereas
      none received adjuvant hormonal therapy postsalvage. Median follow-up time from
      recurrence was 18.7 months (range, 6-84 months). Determination of subsequent
      biochemical failure after brachytherapy was based on the definition by the
      American Society for Therapeutic Radiology and Oncology. RESULTS: Based on the
      Common Terminology Criteria for Adverse Events (CTCAE version 3), 18 patients
      reported Grade 1 to 2 genitourinary symptoms by 3 months postsalvage. Three
      patients developed Grade 3 genitourinary toxicity. Maximum observed
      gastrointestinal toxicity was Grade 2; all cases spontaneously resolved. The 2
      year Kaplan-Meier estimate of biochemical control after recurrence was 89%.
      Thirteen patients have achieved a PSA nadir < or =0.1 ng/ml, but at the time of
      writing this endpoint has not yet been reached for all patients. All patients are
      alive; however 2 have experienced biochemical failure, both with PSA nadirs > or
      =1, and have subsequently been found to have distant metastases. CONCLUSIONS:
      Salvage HDR prostate brachytherapy appears to be feasible and effective.

PMID- 17197120
TI  - Clinical implications of defining the gross tumor volume with combination of CT
      and 18FDG-positron emission tomography in non-small-cell lung cancer.
AB  - PURPOSE: To compare the planning target volume (PTV) definitions for computed
      tomography (CT) vs. positron emission tomography (PET) in non-small-cell lung
      cancer (NSCLC). METHODS AND MATERIALS: A total of 21 patients with NSCLC
      underwent three-dimensional conformal radiotherapy planning. All underwent a
      staging F-18 fluorodeoxyglucose-position emission tomography (18FDG-PET) scan and
      underwent treatment simulation using CT plus a separate planning 18FDG-PET scan.
      Three sets of target volumes were defined: Set 1, CT volumes (CT tumor + staging
      PET nodal disease); Set 2, PET volumes (planning PET tumor {gross tumor volume
      (GTV) = [(0.3069 x mean standardized uptake value) + 0.5853])}; Set 3, composite
      CT-PET volumes (fused CT-PET tumor). Sets 1 and 2 were compared using a matching
      index. Three-dimensional conformal radiotherapy plans were created using the Set
      1 (CT) volumes; and coverage of the Set 3 (composite) volumes was evaluated.
      Separate three-dimensional conformal radiotherapy plans were designed for the Set
      3 volumes. RESULTS: For the primary tumor GTV, the Set 1 (CT) volume was larger
      than the Set 2 (PET) volume in 48%, smaller in 33%, and equal in 19%. The mean
      matching index was 0.65 (35% CT-PET mismatch). Although quantitatively similar,
      the volumes differed qualitatively. The Set 3 (composite) volume was larger than
      either CT or PET alone in 62%, smaller in 24%, and equal in 14%. The dose-volume
      histogram parameters did not differ among the plans for Set 1 (CT) vs. Set 3
      (composite) volumes. Small portions of the Set 3 PTV were significantly
      underdosed in 40% of cases using the CT-only plan. CONCLUSION: Computed
      tomography and PET are complementary and should be obtained in the treatment
      position and fused to define the GTV for NSCLC. Although the quantitative
      absolute target volume is sometimes similar, the qualitative target locations can
      be substantially different, leading to underdosage of the target when planning is
      done using CT alone without PET fusion.

PMID- 17197121
TI  - Immediate postoperative radiotherapy in residual nonfunctioning pituitary
      adenoma: beneficial effect on local control without additional negative impact on
      pituitary function and life expectancy.
AB  - PURPOSE: To demonstrate the benefit of immediate postoperative radiotherapy in
      residual nonfunctioning pituitary adenoma (NFA) in perspective to the need for
      hormonal substitution and life expectancy. METHODS AND MATERIALS: Retrospective
      cohort analysis of 122 patients, operated for NFA between 1979 and 1998.
      Recurrence was defined as regrowth on computed tomography or magnetic resonance
      imaging. The occurrence of hormonal deficiencies was defined as the starting date
      of hormonal substitution therapy. RESULTS: Seventy-six patients had residual NFA
      after surgery and received immediate postoperative radiotherapy (Group 1); three
      patients developed a recurrence, resulting in a 95% local control rate at 10
      years. Twenty-eight patients had residual NFA after surgery, but were followed by
      a wait-and-see policy (Group 2). Sixteen developed a recurrence, resulting in a
      local control rate of 49% at 5 years and 22% at 10 years (p < 0.001 compared with
      Group 1). There were no differences between Group 1 and 2 regarding the need for
      substitution with thyroid hormone, glucocorticoids, and sex hormones before first
      surgery, directly after surgery and at end of follow-up. There were no
      differences in hormone substitution free survival between Group 1 and Group 2
      during the study period after first surgery. Life expectancy was similar in Group
      1 and 2, and their median life expectancy did not differ from median life
      expectancy in the general population. CONCLUSIONS: Immediate postoperative
      radiotherapy provides a marked improvement of local control among patients with
      residual NFA compared with surgery alone, without an additional deleterious
      effect on pituitary function and life expectancy.

PMID- 17197122
TI  - Patterns of failure in patients with locally advanced head and neck cancer
      treated postoperatively with irradiation or concomitant irradiation with
      Mitomycin C and Bleomycin.
AB  - PURPOSE: The long term results and patterns of failure in patients with squamous
      cell head and neck carcinoma (SCHNC) treated in a prospective randomized trial in
      which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin
      (CRT) was compared with radiotherapy only (RT), were analyzed. PATIENTS AND
      METHODS: Between March 1997 and December 2001, 114 eligible patients with Stage
      III or IV SCHNC were randomized. Primary surgical treatment was performed with
      curative intent in all patients. Patients in both groups were postoperatively
      irradiated to the total dose of 56-70 Gy. Chemotherapy included Mitomycin C 15
      mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation. Median
      follow-up was 76 months (48-103 months). RESULTS: At 5 years in the RT and CRT
      arms, the locoregional control was 65% and 88% (p = 0.026), disease-free survival
      33% and 53% (p = 0.035), and overall survival 37% and 55% (p = 0.091)
      respectively. Patients who benefited from chemotherapy were those with high-risk
      factors. The probability of distant metastases was 22% in RT and 20% in CRT arm
      (p = 0.913), of grade III or higher late toxicity 19% in RT and 26% in CRT arm (p
      = 0.52) and of thyroid dysfunction 36% in RT and 56% in CRT arm (p = 0.24). The
      probability to develop a second primary malignancy (SPM) was 34% in the RT and 8%
      in the CRT arm (p = 0.023). One third of deaths were due to infection, but there
      was no difference between the 2 groups. CONCLUSION: With concomitant
      radiochemotherapy, locoregional control and disease free survival were
      significantly improved. Second primary malignancies in the CRT arm compared to RT
      arm were significantly less frequent. The high probability of post treatment
      hypothyroidism in both arms warrants regular laboratory evaluation.

PMID- 17197124
TI  - X-ray-assisted positioning of patients treated by conformal arc radiotherapy for
      prostate cancer: comparison of setup accuracy using implanted markers versus bony
      structures.
AB  - PURPOSE: The aim of this study was to compare setup accuracy of NovalisBody
      stereoscopic X-ray positioning using implanted markers in the prostate vs. bony
      structures in patients treated with dynamic conformal arc radiotherapy for
      prostate cancer. METHODS AND MATERIALS: Random and systematic setup errors (RE
      and SE) of the isocenter with regard to the center of gravity of three fiducial
      markers were measured by means of orthogonal verification films in 120 treatment
      sessions in 12 patients. Positioning was performed using NovalisBody
      semiautomated marker fusion. The results were compared with a control group of
      261 measurements in 15 patients who were positioned with NovalisBody automated
      bone fusion. In addition, interfraction and intrafraction prostate motion was
      registered in the patients with implanted markers. RESULTS: Marker-based X-ray
      positioning resulted in a reduction of RE as well as SE in the anteroposterior,
      craniocaudal, and left-right directions compared with those in the control group.
      The interfraction prostate displacements with regard to the bony pelvis that
      could be avoided by marker positioning ranged between 1.6 and 2.8 mm for RE and
      between 1.3 and 4.3 mm for SE. Intrafraction random and systematic prostate
      movements ranged between 1.4 and 2.4 mm and between 0.8 and 1.3 mm, respectively.
      CONCLUSION: The problem of interfraction prostate motion can be solved by using
      implanted markers. In addition, the NovalisBody X-ray system performs more
      accurately with markers compared with bone fusion. Intrafraction organ motion has
      become the limiting factor for margin reduction around the clinical target
      volume.

PMID- 17197123
TI  - Evaluation of image-guidance protocols in the treatment of head and neck cancers.
AB  - PURPOSE: The aim of this study was to assess the residual setup error of
      different image-guidance (IG) protocols in the alignment of patients with head
      and neck cancer. The protocols differ in the percentage of treatment fractions
      that are associated with image guidance. Using data from patients who were
      treated with daily IG, the residual setup errors for several different protocols
      are retrospectively calculated. METHODS AND MATERIALS: Alignment data from 24
      patients (802 fractions) treated with daily IG on a helical tomotherapy unit were
      analyzed. The difference between the daily setup correction and the setup
      correction that would have been made according to a specific protocol was used to
      calculate the residual setup errors for each protocol. RESULTS: The different
      protocols are generally effective in reducing systematic setup errors. Random
      setup errors are generally not reduced for fractions that are not image guided.
      As a consequence, if every other treatment is image guided, still about 11% of
      all treatments (IG and not IG) are subject to three-dimensional setup errors of
      at least 5 mm. This frequency increases to about 29% if setup errors >3 mm are
      scored. For various protocols that require 15% to 31% of the treatments to be
      image guided, from 50% to 60% and from 26% to 31% of all fractions are subject to
      setup errors >3 mm and >5 mm, respectively. CONCLUSION: Residual setup errors
      reduce with increasing frequency of IG during the course of external-beam
      radiotherapy for head-and-neck cancer patients. The inability to reduce random
      setup errors for fractions that are not image guided results in notable residual
      setup errors.

PMID- 17197125
TI  - Optimizing 4D cone-beam CT acquisition protocol for external beam radiotherapy.
AB  - PURPOSE: Four-dimensional cone-beam computed tomography (4D-CBCT) imaging is
      sensitive to parameters such as gantry rotation speed, number of gantry
      rotations, X-ray pulse rate, and tube current, as well as a patient's breathing
      pattern. The aim of this study is to optimize the image acquisition on a patient
      specific basis while minimizing the scan time and the radiation dose. METHODS AND
      MATERIALS: More than 60 sets of 4D-CBCT images, each with a temporal resolution
      of 10 phases, were acquired using multiple-gantry rotation and slow-gantry
      rotation techniques. The image quality was quantified with a relative root mean
      square error (RE) and correlated with various acquisition settings; specifically,
      varying gantry rotation speed, varying both the rotation speed and the number of
      rotations, and varying both the rotation speed and tube current to keep the
      radiation exposure constant. These experiments were repeated for three different
      respiratory periods. RESULTS: With similar radiation dose, 4D-CBCT images
      acquired with low current and low rotation speed have better quality over images
      obtained with high current and high rotation speed. In general, a one-rotation
      low-speed scan is superior to a two-rotation double-speed scan, even though they
      provide the same number of projections. Furthermore, it is found that the image
      quality behaves monotonically with the relative speed as defined by the gantry
      rotation speed and the patient respiratory period. CONCLUSIONS: The RE curves
      established in this work can be used to predict the 4D-CBCT image quality before
      a scan. This allows the acquisition protocol to be optimized individually to
      balance the desired quality with the associated scanning time and patient
      radiation dose.

PMID- 17197126
TI  - The role and strategy of IMRT in radiotherapy of pelvic tumors: Dose escalation
      and critical organ sparing in prostate cancer.
AB  - PURPOSE: To investigate the intensity-modulated radiotherapy (IMRT) strategy in
      dose escalation of prostate and pelvic lymph nodes. METHODS AND MATERIALS: Plan
      dosimetric data of 10 prostate cancer patients were compared with two-dimensional
      (2D) or IMRT techniques for pelvis (two-dimensional whole pelvic radiation
      therapy [2D-WPRT] or IM-WPRT) to receive 50 Gy or 54 Gy and additional prostate
      boost by three-dimensional conformal radiation therapy or IMRT (3D-PBRT or IM
      PBRT) techniques up to 72 Gy or 78 Gy. Dose-volume histograms (DVHs), normal
      tissue complication probabilities (NTCP) of critical organ, and conformity of
      target volume in various combinations were calculated. RESULTS: In DVH analysis,
      the plans with IM-WPRT (54 Gy) and additional boost up to 78 Gy had lower rectal
      and bladder volume percentage at 50 Gy and 60 Gy, compared with those with 2D
      WPRT (50 Gy) and additional boost up to 72 Gy or 78 Gy. Those with IM-WPRT (54
      Gy) also had better small bowel sparing at 30 Gy and 50 Gy, compared with those
      with 2D-WPRT (50 Gy). In NTCP, those with IM-WPRT and total dose of 78 Gy
      achieved lower complication rates in rectum and small bowel, compared with those
      of 2D-WPRT with total dose of 72 Gy. In conformity, those with IM-WPRT had better
      conformity compared with those with 2D-WPRT with significance (p < 0.005). No
      significant difference in DVHs, NTCP, or conformity was found between IM-PBRT and
      3D-PBRT after IM-WPRT. CONCLUSIONS: Initial pelvic IMRT is the most important
      strategy in dose escalation and critical organ sparing. IM-WPRT is recommended
      for patients requiring WPRT. There is not much benefit for critical organ sparing
      by IMRT after 2D-WPRT.

PMID- 17197128
TI  - Hypofractionated stereotactic body radiation therapy (SBRT) for limited hepatic
      metastases.
AB  - PURPOSE: To evaluate the feasibility and efficacy of hypofractionated
      stereotactic body radiation therapy (SBRT) for the treatment of liver metastases.
      METHODS AND MATERIALS: The records of 69 patients with 174 metastatic liver
      lesions treated with SBRT between April 2001 and October 2004 were reviewed. The
      most common primary tumors were colorectal (n = 20), breast (n = 16), pancreas (n
      = 9), and lung (n = 5). The mean number of lesions treated per patient was 2.5
      (range, 1-6). The longest diameter of the lesions ranged in size from 0.6 to 12.2
      cm (median, 2.7 cm). Dose per fraction ranged from 2 Gy to 6 Gy, with a median
      total dose of 48 Gy (range, 30-55 Gy). Dose was prescribed to the 100% isodose
      line (IDL), with the 80% IDL covering the gross tumor volume with a minimum
      margin of 7 mm. RESULTS: The median follow up was 14.5 months. Sixty patients
      were evaluable for response based on an abdominal computed tomography scan
      obtained at a minimum of 3 months after completion of SBRT. The actuarial overall
      infield local control rate of the irradiated lesions was 76% and 57% at 10 and 20
      months, respectively. The median overall survival time was 14.5 months. The
      progression-free survival rate was 46% and 24% at 6 and 12 months, respectively.
      None of the patients developed Grade 3 or higher toxicity. CONCLUSION:
      Hypofractionated SBRT provides excellent local control with minimal side effects
      in selected patients with limited hepatic metastases.

PMID- 17197127
TI  - Optimal time interval between capecitabine intake and radiotherapy in
      preoperative chemoradiation for locally advanced rectal cancer.
AB  - PURPOSE: Capecitabine and its metabolites reach peak plasma concentrations 1 to 2
      hours after a single oral administration, and concentrations rapidly decrease
      thereafter. We performed a retrospective analysis to find the optimal time
      interval between capecitabine administration and radiotherapy for rectal cancer.
      METHODS AND MATERIALS: The time interval between capecitabine intake and
      radiotherapy was measured in patients who were treated with preoperative
      radiotherapy and concurrent capecitabine for rectal cancer. Patients were
      classified into the following groups. Group A1 included patients who took
      capecitabine 1 hour before radiotherapy, and Group B1 included all other
      patients. Group B1 was then subdivided into Group A2 (patients who took
      capecitabine 2 hours before radiotherapy) and Group B2. Group B2 was further
      divided into Group A3 and Group B3 with the same method. Total mesorectal
      excision was performed 6 weeks after completion of chemoradiation and the
      pathologic response was evaluated. RESULTS: A total of 200 patients were enrolled
      in this study. Pathologic examination showed that Group A1 had higher rates of
      complete regression of primary tumors in the rectum (23.5% vs. 9.6%, p = 0.01),
      good response (44.7% vs. 25.2%, p = 0.006), and lower T stages (p = 0.021)
      compared with Group B1; however, Groups A2 and A3 did not show any improvement
      compared with Groups B2 and B3. Multivariate analysis showed that increases in
      primary tumors in the rectum and good response were only significant when
      capecitabine was administered 1 hour before radiotherapy. CONCLUSION: In
      preoperative chemoradiotherapy for rectal cancer, the pathologic response could
      be improved by administering capecitabine 1 hour before radiotherapy.

PMID- 17197129
TI  - A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam
      radiation therapy for esophageal carcinoma.
AB  - PURPOSE: Concurrent chemotherapy and radiation therapy (RT) are used to treat
      patients with esophageal cancer. The optimal combination of chemotherapeutic
      agents with RT is undefined. We evaluated a combination of capecitabine,
      carboplatin, and paclitaxel with RT in a phase I study. METHODS AND MATERIALS:
      Patients with squamous cell carcinoma or adenocarcinoma of the esophagus
      initially received capecitabine, carboplatin, and paclitaxel with RT (1.8 Gy
      daily to 50.4 Gy). After completion, patients were restaged and evaluated for
      surgery. Primary endpoints included determination of dose-limiting toxicities
      (DLT) and a recommended phase II dose, non-DLT, and preliminary radiographic and
      pathologic response rates. RESULTS: Thirteen patients were enrolled (10 men, 3
      women). All were evaluable for toxicity and efficacy. Two of 3 patients at dose
      level 1 (capecitabine 825 mg/m(2) twice daily on RT days, carboplatin area under
      the curve (AUC) 2 weekly, paclitaxel 60 mg/m(2) weekly) had DLT (both Grade 4
      esophagitis). Of these 3, 2 underwent esophagectomy and had pathologic complete
      response (pCR). Ten patients were then enrolled at dose level -1 (capecitabine
      600 mg/m(2) twice daily, carboplatin AUC 1.5, paclitaxel 45 mg/m(2)). Overall, 3
      of 10 patients at dose level -1 developed DLT (2 Grade 3 esophagitis, 1 Grade 3
      hypotension). Esophagectomy was performed in 6 of 10 patients. All patients had
      pathologic downstaging and 2 of 6 had pCR. CONCLUSIONS: The maximally
      tolerated/recommended phase II doses were capecitabine 600 mg/m(2) twice daily,
      carboplatin AUC 1.5 weekly, and paclitaxel 45 mg/m(2) weekly with RT to 50.4 Gy.
      In our small study, this regimen appears active but is accompanied by significant
      toxicities, primarily esophagitis.

PMID- 17197130
TI  - Rectal cancer delivery of radiotherapy in adequate time and with adequate dose is
      influenced by treatment center, treatment schedule, and gender and is prognostic
      parameter for local control: results of study CAO/ARO/AIO-94.
AB  - PURPOSE: The impact of the delivery of radiotherapy (RT) on treatment results in
      rectal cancer patients is unknown. METHODS AND MATERIALS: The data from 788
      patients with rectal cancer treated within the German CAO/AIO/ARO-94 phase III
      trial were analyzed concerning the impact of the delivery of RT (adequate RT:
      minimal radiation RT dose delivered, 4300 cGy for neoadjuvant RT or 4700 cGy for
      adjuvant RT; completion of RT in <44 days for neoadjuvant RT or <49 days for
      adjuvant RT) in different centers on the locoregional recurrence rate (LRR) and
      disease-free survival (DFS) at 5 years. The LRR, DFS, and delivery of RT were
      analyzed as endpoints in multivariate analysis. RESULTS: A significant difference
      was found between the centers and the delivery of RT. The overall delivery of RT
      was a prognostic factor for the LRR (no RT, 29.6% +/- 7.8%; inadequate RT, 21.2%
      +/- 5.6%; adequate RT, 6.8% +/- 1.4%; p = 0.0001) and DFS (no RT, 55.1% +/- 9.1%;
      inadequate RT, 57.4% +/- 6.3%; adequate RT, 69.1% +/- 2.3%; p = 0.02).
      Postoperatively, delivery of RT was a prognostic factor for LRR on multivariate
      analysis (together with pathologic stage) but not for DFS (independent
      parameters, pathologic stage and age). Preoperatively, on multivariate analysis,
      pathologic stage, but not delivery of RT, was an independent prognostic parameter
      for LRR and DFS (together with adequate chemotherapy). On multivariate analysis,
      the treatment center, treatment schedule (neoadjuvant vs. adjuvant RT), and
      gender were prognostic parameters for adequate RT. CONCLUSION: Delivery of RT
      should be regarded as a prognostic factor for LRR in rectal cancer and is
      influenced by the treatment center, treatment schedule, and patient gender.

PMID- 17197132
TI  - Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine
      for locally advanced unresectable or resected pancreatic cancer: a phase I-II
      study.
AB  - PURPOSE: To determine the safety, efficacy, and tolerability of biweekly
      gemcitabine with concurrent radiotherapy (RT) for resected and locally advanced
      (LA) pancreatic cancer. METHODS AND MATERIALS: Eligible patients had either LA or
      resected pancreatic cancer. Between March 1999 and July 2001, 63 patients (31
      with LA and 32 with resected disease) were treated. Of the 63 patients, 28 were
      enrolled in a Phase I study of increasing radiation doses (35 Gy [n = 7], 43.75
      Gy [n = 11], and 52.5 Gy [n = 10] given within 4, 5, or 6 weeks, respectively, in
      1.75-Gy fractions) concurrently with 40 mg/m(2) gemcitabine biweekly.
      Subsequently, 35 were enrolled in a Phase II study with the addition of induction
      gemcitabine 1000 mg/m(2) within 7 or 8 weeks to concurrent biweekly gemcitabine
      (40 mg/m(2)) and 52.5 Gy RT within 6 weeks. RESULTS: In the LA population, the
      best response observed was a complete response in 1, partial response in 3,
      stable disease in 10, and progressive disease in 17. In the phase II trial,
      gemcitabine plus RT was not delivered to 8 patients because of progression with
      induction gemcitabine alone (n = 5) or by patient request (n = 3). On intent-to
      treat analysis, the median survival in the LA patients was 13.9 months and the 2
      year survival rate was 16.1%. In the resected population, the median progression
      free survival was 8.3 months, the median survival was 18.4 months, and the 2- and
      5-year survival rate was 36% and 19.4%, respectively. The treatment was well
      tolerated; the median gemcitabine dose intensity was 96% of the planned dose in
      the neoadjuvant and concurrent portions of the Phase II study. No treatment
      related deaths occurred. CONCLUSION: Biweekly gemcitabine (40 mg/m(2))
      concurrently with RT (52.5 Gy in 30 fractions of 1.75 Gy) with or without
      induction gemcitabine is safe and tolerable and shows efficacy in patients with
      LA and resected pancreatic cancer.

PMID- 17197133
TI  - Active breathing control (ABC): determination and reduction of breathing-induced
      organ motion in the chest.
AB  - PURPOSE: Extensive radiotherapy volumes for tumors of the chest are partly caused
      by interfractional organ motion. We evaluated the feasibility of respiratory
      observation tools using the active breathing control (ABC) system and the effect
      on breathing cycle regularity and reproducibility. METHODS AND MATERIALS: Thirty
      six patients with unresectable tumors of the chest were selected for evaluation
      of the ABC system. Computed tomography scans were performed at various
      respiratory phases starting at the same couch position without patient movement.
      Threshold levels were set at minimum and maximum volume during normal breathing
      cycles and at a volume defined as shallow breathing, reflecting the subjective
      maximal tolerable reduction of breath volume. To evaluate the extent of organ
      movement, 13 landmarks were considering using commercial software for image
      coregistration. In 4 patients, second examinations were performed during therapy.
      RESULTS: Investigating the differences in a normal breathing cycle versus shallow
      breathing, a statistically significant reduction of respiratory motion in the
      upper, middle, and lower regions of the chest could be detected, representing
      potential movement reduction achieved through reduced breath volume. Evaluating
      interfraction reproducibility, the mean displacement ranged between 0.24 mm
      (chest wall/tracheal bifurcation) to 3.5 mm (diaphragm) for expiration and
      shallow breathing and 0.24 mm (chest wall) to 5.25 mm (diaphragm) for normal
      inspiration. CONCLUSIONS: By modifying regularity of the respiratory cycle
      through reduction of breath volume, a significant and reproducible reduction of
      chest and diaphragm motion is possible, enabling reduction of treatment planning
      margins.

PMID- 17197131
TI  - Radiation dose and late failures in prostate cancer.
AB  - PURPOSE: To quantify the impact of radiation dose escalation on the timing of
      biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated
      with radiotherapy (RT) alone. METHODS: The data from 667 men with clinically
      localized intermediate- and high-risk prostate cancer treated with three
      dimensional conformal RT alone were retrospectively analyzed. The interval hazard
      rates of DM and BF, using the American Society for Therapeutic Radiology and
      Oncology (ASTRO) and Phoenix (nadir + 2) definitions, were determined. The median
      follow-up was 77 months. RESULTS: Multivariate analysis showed that increasing
      radiation dose was independently associated with decreased ASTRO BF (p < 0.0001),
      nadir + 2 BF (p = 0.001), and DM (p = 0.006). The preponderance (85%) of ASTRO BF
      occurred at < or =4 years after RT, and nadir + 2 BF was more evenly spread
      throughout Years 1-10, with 55% of BF in < or =4 years. Radiation dose escalation
      caused a shift in the BF from earlier to later years. The interval hazard
      function for DM appeared to be biphasic (early and late peaks) overall and for
      the <74-Gy group. In patients receiving > or =74 Gy, a reduction occurred in the
      risk of DM in the early and late waves, although the late wave appeared reduced
      to a greater degree. CONCLUSION: The ASTRO definition of BF systematically
      underestimated late BF because of backdating. Radiation dose escalation
      diminished and delayed BF; the delay suggested that local persistence may still
      be present in some patients. For DM, a greater radiation dose reduced the early
      and late waves, suggesting that persistence of local disease contributed to both.

PMID- 17197134
TI  - Gene expression patterns in Euglena gracilis: insights into the cellular response
      to environmental stress.
AB  - To better understand Euglena gracilis gene expression under different stress
      conditions (Chromium, Streptomycin or darkness), we undertook a survey of the E.
      gracilis transcriptome by cDNA sequencing and microarray analysis. First, we
      constructed a non-normalized cDNA library from the E. gracilis UTEX strain and
      sequenced a total of 1000 cDNAs. Six hundred and ten of these ESTs were similar
      to either Plantae or Protistae genes (e-value<e(-10)). Second, microarrays were
      built by spotting all the ESTs onto mirror slides. Microarray expression analysis
      indicated that 90 out of those 610 ESTs changed their expression level in
      response to different stress treatments (p<0.05). In addition, we detected 10
      ESTs that changed expression levels irrespective of the tested stress. These may
      be considered as part of a larger set of stress-related genes in E. gracilis.
      Finally, we identified 23 unknown ESTs (U-ESTs) following the expression profiles
      of these putative stress-related genes suggesting that they could be related to
      the cellular mechanism of stress response.

PMID- 17197135
TI  - An outbreak of equine influenza virus in vaccinated horses in Italy is due to an
      H3N8 strain closely related to recent North American representatives of the
      Florida sub-lineage.
AB  - In December 2005, equine influenza virus infection was confirmed as the cause of
      clinical respiratory disease in vaccinated horses in Apulia, Italy. The infected
      horses had been vaccinated with a vaccine that contained strains representatives
      from both the European (A/eq/Suffolk/89) and American (A/eq/Newmarket/1/93) H3N8
      influenza virus lineages, and the H7N7 strain A/eq/Praga/56. Genetic
      characterization of the hemagglutinin (HA) and neuraminidase (NA) genes of the
      virus from the outbreak, indicated that the isolate (A/eq/Bari/2005) was an H3N8
      strain closely related to recent representatives (Kentucky/5/02-like) of the
      American sub-lineage Florida, that was introduced in Italy through movement of
      infected horses from a large outbreak described in 2003 in United Kingdom. Strain
      A/eq/Bari/2005 displayed 9 amino acid changes in the HA1 subunit protein with
      respect to the reference American strain A/eq/Newmarket/1/93 contained in the
      vaccine. Four changes were localized in the antigenic regions C-D and likely
      accounted for the vaccine failure.

PMID- 17197137
TI  - Photo-irradiation of Aloe vera by UVA--formation of free radicals, singlet
      oxygen, superoxide, and induction of lipid peroxidation.
AB  - Aloe vera whole leaf extracts are incorporated into a wide variety of topically
      applied commercial products. Aloe vera whole leaf extracts may contain
      anthraquinones, which have been shown to generate reactive oxygen species in the
      presence of ultraviolet A (UVA) light. Exposure to UVA light alone can also
      generate reactive oxygen species and is associated with photo-damaged and photo
      aged skin in humans. This paper examines the photochemical properties of two Aloe
      vera whole leaf extracts that differed in their anthraquinone content. In the
      presence of methyl linoleate, the UVA irradiation of Aloe vera leaf extracts
      induced lipid peroxidation. The amounts of lipid peroxides formed were higher in
      the Aloe vera leaf extract that contained lower amounts of anthraquinones.
      Superoxide dismutase and sodium azide inhibited and deuterium oxide enhanced the
      formation of lipid peroxides, suggesting that singlet oxygen and superoxide were
      involved in the mechanism. Spin trapping electron spin resonance (ESR)
      spectroscopy was used to investigate the generation of free radicals by the UVA
      photo-irradiated Aloe vera plant extracts. ESR measurements indicated that the
      UVA photo-irradiation of Aloe vera plant extracts produced carbon-centered free
      radicals. These results suggest that humans exposed to products that contain Aloe
      vera whole leaf extracts may have enhanced sensitivity to ultraviolet light.

PMID- 17197138
TI  - Beta-aminoketones as prodrugs with pH-controlled activation.
AB  - N-Mannich bases have been widely applied as prodrugs of amine drugs. The
      analogous C-Mannich bases (beta-aminoketones) have received rather less attention
      probably because they are not sufficiently susceptible to elimination at pHs
      encountered in vivo. Compounds in which there is a thermodynamic advantage to
      elimination may be an exception. In this study, the physicochemical
      characteristics of a series of Michael amino addition adducts of chalcone and
      other carbonyl compounds is explored. The ketone adducts rapidly eliminate at
      around pH 7.4 (t(1/2) < 15 min) releasing the amine and the ketone but they are
      stable under acidic conditions. The Michael adducts are more lipophilic than the
      parent amines and have significantly suppressed ionisation characteristics at
      biologically relevant pH values.

PMID- 17197136
TI  - Acute toxicity and biodistribution of different sized titanium dioxide particles
      in mice after oral administration.
AB  - In order to evaluate the toxicity of TiO(2) particles, the acute toxicity of nano
      sized TiO(2) particles (25 and 80nm) on adult mice was investigated compared with
      fine TiO(2) particles (155nm). Due to the low toxicity, a fixed large dose of
      5g/kg body weight of TiO(2) suspensions was administrated by a single oral gavage
      according to the OECD procedure. In 2 weeks, TiO(2) particles showed no obvious
      acute toxicity. However, the female mice showed high coefficients of liver in the
      nano-sized (25 and 80nm) groups. The changes of serum biochemical parameters
      (ALT/AST, LDH) and pathology (hydropic degeneration around the central vein and
      the spotty necrosis of hepatocytes) of liver indicated that the hepatic injury
      was induced after exposure to mass different-sized TiO(2) particles. In addition,
      the nephrotoxicity like increased BUN level and pathology change of kidneys was
      also observed in the experimental groups. The significant change of serum LDH and
      alpha-HBDH in 25 and 80nm groups showed the myocardial damage compared with the
      control group. However, there are no abnormal pathology changes in the heart,
      lung, testicle (ovary), and spleen tissues. Biodistribution experiment showed
      that TiO(2) mainly retained in the liver, spleen, kidneys, and lung tissues,
      which indicated that TiO(2) particles could be transported to other tissues and
      organs after uptake by gastrointestinal tract.

PMID- 17197140
TI  - Factors influencing intestinal microparticle uptake in vivo.
AB  - The aim of this study is to compare microparticle uptake in animals of different
      ages, gender and species and at different time points. The 2mum latex/in vivo in
      situ model uses the observation of animal responses or post-mortem changes and
      also particle identification by fluorescence microscopy in nine sequential
      intestinal segments and secondary sites. The wide size range of animals studied
      requires particle numbers in tissue compartments to be related to intestinal
      tissue section area through a circumference measurement. Area under the curve
      (AUC) data for particles in intestinal tissue are plotted against measurements of
      intestinal length, allowing comparisons to be made across different ages and
      species and between males and females. The percentage uptake of administered dose
      and particle numbers in macerated tissue are also reported. Some parameters, in
      particular species, do not appear to affect the extent of microparticle uptake,
      which ranges from 0.12 to 0.32% of the administered dose. Particle uptake does,
      however, vary with age, being significantly greater in young adult males (7
      weeks) than in younger (3 weeks) and older (17 and 52 weeks) age groups. It is
      concluded that age is more important in determining the extent of uptake than
      gender or species.

PMID- 17197141
TI  - Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic
      rats.
AB  - The present study was designed to investigate the hypoglycemic and hypolipidemic
      properties of an ethanolic extract of Cichorium intybus (CIE) which is widely
      used in India as a traditional treatment for diabetes mellitus. Male Sprague
      Dawley rats aged 9 weeks (160-200 g) were administered with streptozotocin (STZ,
      50mg/kg) intraperitoneally to induce experimental diabetes. The Cichorium intybus
      whole plant was exhaustively extracted with 80% ethanol, concentrated at 40
      degrees C using a rotavapor and freeze dried to get powder. Hypoglycemic effects
      of CIE were observed in an oral glucose tolerance test (OGTT) in which, a dose of
      125 mg of plant extract/kg body weight exhibited the most potent hypoglycemic
      effect. Moreover, daily administration of CIE (125 mg/kg) for 14 days to diabetic
      rats attenuated serum glucose by 20%, triglycerides by 91% and total cholesterol
      by 16%. However, there was no change in serum insulin levels, which ruled out the
      possibility that CIE induces insulin secretion from pancreatic beta-cells. In
      addition, hepatic glucose-6-phosphatase activity (Glc-6-Pase) was markedly
      reduced by CIE when compared to the control group. The reduction in the hepatic
      Glc-6-Pase activity could decrease hepatic glucose production, which in turn
      results in lower concentration of blood glucose in CIE-treated diabetic rats. In
      conclusion, our results support the traditional belief that Cichorium intybus
      could ameliorate diabetic state.

PMID- 17197142
TI  - [Imported severe malaria in adults: a retrospective study of ten cases admitted
      to intensive care units in Casablanca].
AB  - INTRODUCTION: We report a retrospective study in the medical intensive care unit
      of the Casablanca Ibn-Rochd University hospital. MATERIAL AND METHODS: All
      patients over 14 years of age with falciparum malaria, who were admitted to ICUs
      between 1996 and 2001, were included. The main epidemiological features, criteria
      of admission, treatment, and outcome were investigated. RESULTS: Ten patients
      were included for severe imported malaria. The mean age was 32+/-4 years. All
      patients had acquired falciparum malaria in sub-Saharan Africa. Chemoprophylaxis
      was inadequate in all patients. The mean time from symptom onset to treatment
      initiation was 9+/-2 days. Criteria of admission were impaired consciousness (7),
      acute renal failure (4), and respiratory distress (3). The most worrying factors
      were the severity of consciousness disorders, the acute respiratory distress
      syndrome, the metabolic acidosis, and the refractory shock. All patients
      presented with nosocomial respiratory infection related to Gram-negative bacilli,
      in the evolution. All patients received quinine therapy with loading dose and
      symptomatic treatment. Five patients died. CONCLUSION: The lethality of severe
      imported malaria is still high despite optimal management in ICUs. Improving
      chemoprophylaxis and an earlier diagnosis may reduce significantly the mortality
      rate.

PMID- 17197145
TI  - CD8 T cell clonal expansions & aging: a heterogeneous phenomenon with a common
      outcome.
AB  - A highly diverse CD8 T cell repertoire is thought to be critical for maintaining
      appropriate immune defenses against a variety of pathogens. However, in many aged
      individuals, the diversity of T cell receptors is significantly reduced by the
      presence of large, monoclonal expansions of CD8 memory T cells. While ongoing
      research is focused on understanding the molecular alterations in these
      expansions, one major hurdle to this goal is the apparent heterogeneity of CD8
      clonal expansions, which is apparent even in reductionist systems. In this
      review, we discuss current evidence that CD8 clonal expansions are a
      heterogeneous phenomenon, and our evolving understanding of what this
      heterogeneity tells us about CD8 memory T cell homeostasis and how it is altered
      in aged individuals.

PMID- 17197144
TI  - Cancer vaccines in old age.
AB  - The incidence of cancer has increased over the last decade, mainly due to an
      increase in the elderly population. Vaccine therapy for cancer is less toxic than
      chemotherapy or radiation and could be, therefore, especially effective in older,
      more frail cancer patients. However, it has been shown that older individuals do
      not respond to vaccine therapy as well as younger adults. This has been
      attributed to T cell unresponsiveness, a phenomenon also observed in cancer
      patients per se. This review summarizes the current knowledge of T cell
      unresponsiveness in cancer patients and elderly, the results of cancer
      vaccination in preclinical models and in clinical trials, and recent data of
      cancer vaccination at young and old age in preclinical models. Finally,
      experimental approaches will be proposed how to make cancer vaccines more
      effective at older age.

PMID- 17197143
TI  - Aging and CD8+ T cell immunity to respiratory virus infections.
AB  - The capacity of the immune system to mediate effective immune responses to
      pathogens declines with age. In the case of immune responses to newly encountered
      antigens, several studies have demonstrated that this decline reflects both a
      loss of naive T cells and changes in the repertoire and function of these cells
      over time. However, comparatively little is known about the impact of age on
      established memory T cells pools. Here we discuss age-related changes in memory
      CD8(+) T cell pools elicited by influenza and parainfluenza viruses and the
      impact of these changes on immunity in general.

PMID- 17197146
TI  - Inflammatory chronic disease of the colon: how to image.
AB  - Inflammatory bowel disease, including Crohn's disease and UC, is a chronic
      disorder of the gastrointestinal tract. The inflammatory process in UC is
      confined to the mucosa and submucosa and it involves only the colon. In contrast,
      in Crohn's disease the inflammation process extends through the bowel wall layers
      and it can involve any part of gastrointestinal tract. Moreover, inflammatory
      bowel disease of the colon may be associated with complications, such as toxic
      megacolon, fulminant colitis, acute bleeding, fistulas and abscesses.
      Radiographic imaging studies are useful for the diagnosis of inflammatory bowel
      disease, and may be used to assess the extent and severity of disease, rule out
      complications, and monitor the response to therapy. The double-contrast barium
      study is a valuable technique for diagnosing inflammatory bowel disease colonic
      alterations, even in patients with early mucosal abnormalities. The earliest
      finding of UC is characterized by a fine granular appeareance of the colonic
      mucosa, usually involving the rectosigmoid junction. In chronic UC double
      contrast enema may reveal marked colonic shortening with tubular narrowing of the
      bowel and loss of haustration. The earliest radiographics findings of Crohn's
      disease are represented by aphthous ulcers. As disease progresses, aphthous
      ulcers may enlarge and coalesce to form stellate or linear areas of ulceration.
      In advanced Crohn's disease, transmural ulceration may lead to the development of
      fissures, sinus tracts, fistulas, and abscesses. Cross sectional studies such as
      computed tomography, magnetic resonance imaging and sometimes ultrasound, are
      useful alternative tools not only in the assessment of bowel wall abnormalities,
      but also for the assessment of extraluminal alterations in patients with advanced
      disease.

PMID- 17197147
TI  - Legionella impletisoli sp. nov. and Legionella yabuuchiae sp. nov., isolated from
      soils contaminated with industrial wastes in Japan.
AB  - In this study, we tried to isolate legionellae from nine Legionella DNA-positive
      soil samples collected from four different sites contaminated with industrial
      wastes in Japan. Using culture methods with or without Acanthamoeba culbertsoni,
      a total of 22 isolates of legionellae were obtained from five of the nine
      samples. Identification of species and/or serogroups (SGs), performed by DNA-DNA
      hybridization and agglutination tests, revealed that the 22 isolates consisted of
      ten isolates of Legionella pneumophila including five SGs, five Legionella
      feeleii, and one each of Legionella dumoffii, Legionella longbeachae, and
      Legionella jamestownensis. The species of the remaining four isolates (strains
      OA1-1, -2, -3, and -4) could not be determined, suggesting that these isolates
      may belong to new species. The 16S rDNA sequences (1476-1488bp) of the isolates
      had similarities of less than 95.0% compared to other Legionella species. A
      phylogenetic tree created by analysis of the 16S rRNA (1270bp) genes demonstrated
      that the isolates formed distinct clusters within the genus Legionella.
      Quantitative DNA-DNA hybridization tests on the OA1 strains indicated that OA1-1
      should be categorized as a new taxon, whereas OA1-2, -3, and -4 were also
      genetically independent in another taxon. Based on the evaluated phenotypic and
      phylogenetic characteristics, it is proposed that one of these isolates from the
      soils, OA1-1, be classified as a novel species, Legionella impletisoli sp. nov.;
      the type strain is strain OA1-1(T) (=JCM 13919(T)=DSMZ 18493(T)). The remaining
      three isolates belong to another novel Legionella species, Legionella yabuuchiae
      sp. nov.; the type strain is strain OA1-2(T) (=JCM 14148(T)=DSMZ 18492(T)). This
      is the first report on the isolation of legionellae from soils contaminated with
      industrial wastes.

PMID- 17197148
TI  - Automated determination of flutamide by a validated flow-injection method:
      application to dissolution studies of pharmaceutical tablets.
AB  - The first flow-injection (FI) method for the determination of flutamide--a potent
      antiandrogen used for the treatment of prostate cancer--is reported. The method
      is based on the direct measurement of the absorbance of the analyte at 310 nm
      under flow conditions. Parameters affecting the determination such as detection
      wavelength, sample injection volume and flow rate were studied and optimized. The
      assay was validated (linearity, limits of detection and quantitation, accuracy,
      repeatability, reproducibility and selectivity) for the dissolution studies of
      flutamide-containing tablets during stability testing. The results were in good
      agreement with high performance liquid chromatography (HPLC) used as a reference
      method.

PMID- 17197149
TI  - Insect cells for human food.
AB  - There is a need for novel protein sources. Insects are a possible interesting
      source of protein. They are nutritious in terms of protein (40-75 g/100g dry
      weight) and minerals. Insect protein is of high quality and has a high
      digestibility (77-98%) and concentration of essential amino acids (46-96% of the
      nutritional profile). Also insect cells may be a promising novel source of
      protein. Choice of cell line, growth conditions and use of the baculovirus
      expression system opens up possibilities to engineer the nutritional value of the
      biomass. The technological limits as well as consumer acceptance of insect cell
      based food remains to be investigated.

PMID- 17197150
TI  - Proline reduces brain cytochrome c oxidase: prevention by antioxidants.
AB  - In the present study, we initially investigated the in vivo (acute and chronic)
      and in vitro effects of proline on cytochrome c oxidase (complex IV) activity in
      rat cerebral cortex to test the hypothesis that proline might alter energy
      metabolism and that this alteration could be provoked by oxidative stress. The
      action of alpha-tocopherol and ascorbic acid on the effects produced by proline
      was also evaluated. For acute administration, 29- and 60-day-old rats received
      one subcutaneous injection of proline (18.2 micromol/g body weight) or an
      equivalent volume of 0.9% saline solution (control) and were sacrificed 1h later.
      For chronic treatment, proline was injected subcutaneously twice a day at 10h
      intervals from the 6(th) to the 28(th) day of age. Rats were sacrificed 12h
      (29(th)) or 31 days (60(th)) after the last injection. Results showed that acute
      administration of proline significantly diminished the activity of cytochrome c
      oxidase in the cerebral cortex of 29- and 60-day-old rats. On the other hand,
      chronic hyperprolinemia reduced this complex activity only on day 29, but not on
      the 60(th) day of life. In another set of experiments, 22-day-old rats or 53-day
      old rats were pretreated for 1 week with daily intraperitoneal administration of
      alpha-tocopherol (40 mg/kg) and ascorbic acid (100mg/kg) or saline. Twelve hours
      after the last antioxidant injection, rats received a single injection of proline
      or saline and were killed 1h later. In parallel to chronic treatment, rats
      received a daily intraperitoneal injection of alpha-tocopherol and ascorbic acid
      from the 6(th) to the 28(th) day of life and were killed 12h after the last
      injection. Results showed that the pretreatment with alpha-tocopherol and
      ascorbic acid before acute proline administration or concomitant to chronic
      proline administration significantly prevented these effects. We also observed
      that proline (3.0 microM-1.0 mM) when added to the incubation medium (in vitro
      studies) did not alter cytochrome c oxidase activity. Data suggest that the
      inhibitory effect of proline on cytochrome c oxidase activity is possibly
      associated with oxidative stress and that this parameter may be involved in the
      brain dysfunction observed in hyperprolinemia.

PMID- 17197151
TI  - Survival after negative sentinel lymph node biopsy in breast cancer at least
      equivalent to after negative extensive axillary dissection.
AB  - AIM: Sentinel lymph node biopsy (SLNB) without completion axillary lymph node
      dissection (ALND) is replacing ALND as the axillary staging procedure of choice
      in breast cancer patients with a clinically negative axilla even though it is
      unclear whether this influences patient survival. Our aim was to compare the
      survival of breast cancer patients with a negative SLNB without completion ALND
      to that of extensive ALND-negative patients. METHODS: Eindhoven Cancer Registry
      data on breast cancer patients diagnosed between 1989 and 2002 with follow-up to
      1 January 2005 was used. Survival was compared between 880 SLNB-negative women
      (median follow-up 3.6years) without completion ALND and 1681 ALND-negative women
      (median follow-up 7.7years) with at least 10 axillary nodes removed. Conclusions
      were made after correcting for age, tumour size, tumour location, tumour
      histology, tumour grade, mitotic activity index (MAI), hormone receptor status,
      and local and systemic treatment in uni- and multivariate analyses. RESULTS:
      Crude 5-year survival rates were 85% for ALND-negative and 89% for SLNB-negative
      breast cancer patients (p=0.026). After correction for potential confounders in a
      multivariate Cox regression analyses, the hazard ratio for overall mortality of
      ALND-negative compared to SLNB-negative patients without completion ALND was 1.23
      (95% confidence interval: 0.93-1.64). CONCLUSION: Survival after a SLNB without
      completion ALND is at least equivalent to after an extensive ALND in node
      negative breast cancer patients. This means that the SLNB only can safely replace
      ALND as the procedure of choice for axillary staging in breast cancer patients
      with a clinically negative axilla.

PMID- 17197152
TI  - Moderators of environmental intervention effects on diet and activity in youth.
AB  - BACKGROUND: The complexity of the relationship between environmental factors on
      the one hand and dietary behavior and physical activity on the other necessitates
      the search for moderators of environmental influences. The current evidence base
      is reviewed regarding potential moderating factors in the effectiveness of
      environmental interventions aimed at diet and/or physical activity of children
      and adolescents. METHODS: The following databases were used: (1) Medline, (2)
      PubMed, (3) PsychInfo, (4) Web of Science, and (5) ERIC. Additionally, all
      potentially relevant references in recent reviews were checked. RESULTS: Of the
      41 studies included in the review, only seven studies (17%) were identified that
      reported tests of potential moderators of intervention effects. Gender proved to
      be the most frequently studied potential moderator. Additionally, race, age, and
      site have been studied regarding their potential role in modifying the effect of
      environmental interventions. DISCUSSION: The small number of studies identified
      in this review prohibited us from attempting to formulate a conclusion on
      differential environment-behavior relationships in distinct subgroups. Rather
      than being an exception, it is argued that tests of effect modifiers should
      become common practice in behavioral nutrition and physical activity research to
      increase our understanding of mechanisms of behavior change and to optimize
      interventions.

PMID- 17197154
TI  - [Tako-tsubo syndrome: a case report].

PMID- 17197153
TI  - Patterns and correlates of physical activity and nutrition behaviors in
      adolescents.
AB  - BACKGROUND: Knowledge of the prevalence, clustering, and correlates of multiple
      adolescent health behaviors can inform the design of health promotion
      interventions. METHODS: A cross-sectional design was used to assess 878
      adolescents aged 11 to 15 years (53.6% girls, 58% non-Hispanic white) recruited
      in primary care clinics in 2001-2002. Adolescent physical activity (assessed with
      accelerometers), television viewing time (reported), percent calories from fat,
      and servings of fruits and vegetables (assessed with multiple 24-hour recalls)
      were dichotomized into meeting or not meeting national guidelines. Parent health
      behaviors were assessed with self-reported measures. Analyses were conducted in
      2006. RESULTS: Fifty-five percent of adolescents did not meet the physical
      activity guideline, and 30% exceeded 2 hours daily of television viewing time,
      with boys more active and less sedentary than girls (p <0.01). The majority of
      the adolescents did not meet dietary guidelines. Nearly 80% had multiple risk
      behaviors and only 2% met all four guidelines. The number of risk behaviors was
      associated with being older and being at risk for overweight or being overweight,
      for boys and girls (p <0.05). Two parent health behaviors-history of smoking and
      failure to meet the fruits and vegetables guideline-were significantly associated
      with a higher number of risk behaviors for girls (p <0.05). CONCLUSIONS: Eight of
      ten adolescents in this sample failed to meet guidelines for two or more diet,
      physical activity, and sedentary risk behaviors. Some parent health behaviors,
      along with the adolescent's weight status and age, were associated with a higher
      number of adolescent health risk behaviors.

PMID- 17197155
TI  - Bacillus cereus strains fall into two clusters (one closely and one more
      distantly related) to Bacillus anthracis according to amino acid substitutions in
      small acid-soluble proteins as determined by tandem mass spectrometry.
AB  - Small acid-soluble proteins (SASPs) are located in the core region of Bacillus
      spores and have been previously demonstrated as reliable biomarkers for
      differentiating Bacillus anthracis and Bacillus cereus. Using MS and MS-MS
      analysis of SASPs further phylogenetic correlations among B. anthracis and B.
      cereus strains are described here. ESI was demonstrated to be a more
      comprehensive method, allowing for the analysis of intact proteins in both MS and
      MS-MS mode, thus providing molecular weight (MW) and sequence information in a
      single analysis, and requiring almost no sample preparation. MALDI MS was used
      for determination of MW of intact proteins; however, MS-MS analysis can only be
      achieved after enzymatic digestion of these proteins. It was demonstrated that
      the combination of the two different approaches provides confirmatory and
      complementary information, allowing for unambiguous protein characterization and
      sequencing. This study established that B. cereus strains fall into two clusters
      (one closely and one more distantly related) to B. anthracis as exhibited by
      amino acid substitutions. The closely related cluster was characterized by a beta
      SASP with a single amino acid substitution, localized either close to the C
      terminus (phenylalanine-->tyrosine, 16 masses change) or close to the N terminus
      (serine-->alanine serine, also 16 masses change). The more distantly related
      cluster displayed both amino acid substitutions (32 masses change). One strain of
      B. cereus isolated from a patient with severe pneumonia (an anthrax-like disease)
      fell into the more distantly related cluster implying that pathogenicity and
      phylogenicity are not necessarily correlated features. Unlike PCR and DNA
      sequencing, protein sequence variation assessed by ESI MS-MS, essentially occurs
      in real-time, and involves simply extracting the protein and injecting into the
      instrument for analysis.

PMID- 17197156
TI  - The effect of sulfur dioxide inhalation on active avoidance learning, antioxidant
      status and lipid peroxidation during aging.
AB  - The effect of SO2 was examined on active avoidance learning, thiobarbituric acid
      reactive substances (TBARS), and the activities of Cu, Zn superoxide dismutase
      (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in young (3 months),
      middle-age (12 months ), and old (24 months) Swiss male albino rats. Ten ppm SO2
      was administered to the animals of SO2 groups in an exposure chamber for 1 h/day
      x 7 days/week x 6 weeks while control groups were exposed to filtered air in the
      same condition. The most prominent effect of aging on active performance was also
      observed in the older group. SO2 exposure significantly decreased the active
      avoidance learning in the young group, but it had no effect on this parameter in
      the middle-aged and the older group compared with their corresponding control
      groups. SO2 exposure resulted in increased levels of Cu, Zn-SOD activity while
      decreased level of GSH-Px activity in all experimental groups compared with their
      corresponding control groups. CAT activities were unaltered. TBARS levels of all
      SO2 exposed groups were significantly increased compared with their respective
      control groups. In conclusion, results from the present research showed that SO2
      exposure resulted in an increase in the lipid peroxidation and caused alterations
      in antioxidant enzyme activities. Additionally, SO2 exposure impaired cognitive
      function only in the young rats during the acquisition phase of active avoidance
      learning.

PMID- 17197157
TI  - SMAD3 expression is regulated by mitogen-activated protein kinase kinase-1 in
      epithelial and smooth muscle cells.
AB  - SMAD3 is a transcription factor that mediates TGF-beta1 signaling and is known to
      be important in many of the cellular processes that regulate fibrosis and
      inflammation. Although several studies have examined SMAD3 activation, little is
      known about the control of SMAD3 expression. It is well established that the
      mitogen-activated protein kinase (MAPK) pathway is responsive to TGF-beta1
      stimulation and coordinates with SMAD signaling in many cases; therefore, the
      hypothesis of this study is that the MAPK pathway will be involved in the
      regulation of SMAD3 expression. Using a SMAD3 promoter construct, we demonstrate
      that inhibition of either c-Jun-N-terminal kinase (JNK) or p38 activity has
      little effect on SMAD3 promoter function. Inhibition of mitogen-activated protein
      kinase kinase-1 (MEK1) with either PD98059 or UO126, however, results in a
      substantial dose-dependent inhibition of SMAD3 promoter activity. Further studies
      confirm that promoter activity correlates with protein expression by
      demonstrating reduced SMAD3 protein expression in A549 cells and airway smooth
      muscle cells after treatment with MEK1 inhibitors. Positive regulation of SMAD3
      expression is also demonstrated by expression of a constitutively active (ca)
      MEK1 construct, where the presence of ca-MEK1 resulted in increased SMAD3 protein
      expression. These data lead to the conclusion that MEK1 is an important regulator
      of SMAD3 expression.

PMID- 17197158
TI  - The PH domain containing protein CKIP-1 binds to IFP35 and Nmi and is involved in
      cytokine signaling.
AB  - The pleckstrin homology domain-containing protein CKIP-1 is implicated in
      regulation of cell differentiation, apoptosis, cytoskeleton as well as
      recruitment of CK2 and ATM kinases to plasma membrane. Protein-protein
      interactions of CKIP-1 were required for these functions. Here we identify the
      IFN-induced protein IFP35 and its homologue Nmi as two novel CKIP-1 interacting
      partners. The NID domains of IFP35 and Nmi are required for the interactions.
      Similar to IFP35 and Nmi, CKIP-1 can be up-regulated dramatically by IFN-gamma
      and IL-2 and form homodimer and homotrimer in vivo. Nmi stabilizes IFP35, whereas
      CKIP-1 destabilizes IFP35 via inhibiting IFP35-Nmi interaction. The ratio of Nmi
      to CKIP-1 determines the stability of IFP35 and control cytokine signaling in a
      novel mechanism. Importantly, similar to Nmi and contrast to IFP35, CKIP-1
      inhibits tumor cell growth and Akt-mediated cell survival. Thus, our results
      provide a novel role of CKIP-1 in cytokine signaling response and the biochemical
      mechanism, by which two previously identified modulators IFP35 and Nmi are
      involved via interactions.

PMID- 17197159
TI  - Terrein, a fungal metabolite, inhibits the epidermal proliferation of skin
      equivalents.

PMID- 17197160
TI  - The effect of APOA5 and APOC3 variants on lipid parameters in European Whites,
      Indian Asians and Afro-Caribbeans with type 2 diabetes.
AB  - Common variants in APOA5 and APOC3 have been associated with differences in
      plasma triglyceride (TG) levels in healthy individuals. The aim of this study was
      to examine the association of APOA5 (-1131T>C, S19W) and APOC3 (-482C>T, 1100C>T)
      polymorphisms in patients with type 2 diabetes (T2D) of European White (EW)
      (n=931), Indian Asian (IA) (n=610) and Afro-Caribbean (AC) (n=167) origin, with
      lipid and T2D parameters. Rare allele frequencies and linkage disequilibrium
      differed significantly amongst ethnic groups. Compared to APOA5 -1131T and 19S
      homozygotes, -1131C and 19W carriers had higher TGs in all groups, but this
      effect was only statistically significant for the -1131C in the EWs (P=0.04) and
      19W in the IAs (P<0.001). APOC3 SNPs showed no significant association with lipid
      levels in any ethnic group. While haplotypes carrying -1131C allele showed
      significant TG-raising in the EWs only, the 19W defined haplotype showed
      significant TG-raising in both IAs and EWs. Comparing all four SNPs in EW T2D
      subjects with healthy EWs (n=2579), the APOC3 1100C>T frequency was significantly
      higher in T2D [0.26 (0.24, 0.28)] vs. healthy EWs [0.22 (0.20, 0.23)], P=0.001.
      While the variable size effects of the two APOA5 SNPs on TG levels may result
      from ethnically different gene-gene or gene-environment interactions, APOA5 and
      APOC3 variants did not affect parameters of T2D. However, comparison between EWs
      with T2D and healthy EWs suggest APOC3 1100C>T is associated with increased risk
      of diabetes probably through mechanisms other than direct effects on TG.

PMID- 17197161
TI  - Effects of lung surfactants on rifampicin release rate from monodisperse
      rifampicin-loaded PLGA microspheres.
AB  - We have prepared inhalable and monodisperse poly(lactide-co-glycolide) (PLGA)
      microspheres targeting tubercle bacilli residing in alveolar macrophages. The
      effects of pulmonary surfactant on the rifampicin (RFP) release rate from RFP
      loaded poly (lactide-co-glycolide) microspheres were studied. Also, those of
      their surface properties of RFP-loaded PLGA microspheres were studied. The RFP
      release from RFP/PLGA microspheres was accelerated by adsorption of pulmonary
      surfactant on the particle surface. The fastest RFP release rate was observed
      from pulmonary surfactant-adsorbed PLGA particles in pH 7.4 buffer solution
      compared with those in pH 4.0 buffer solution and saline solution. The slowest
      release rate was observed in the case when saline solution was used as dispersion
      phase of RFP/PLGA microspheres, although RFP release rate increased by the
      addition of pulmonary surfactant. From these results it is suggested that when
      RFP/PLGA microspheres are administrated by inhalation, the RFP release rates from
      the particles which are not taken up by alveolar macrophages and remain in the
      alveoli will be small. On the other hand, the RFP release rates and release
      amounts will be high after RFP/PLGA microspheres are taken up by alveolar
      macrophages existing in phagosomes, but they become relatively small after
      RFP/PLGA microspheres move into phagosome-lysosomes by the fusion of phagosomes
      with lysosomes. The absolute values of the electrophoretic mobility of PLGA
      microspheres increased by the adsorption of pulmonary surfactants on the surfaces
      of PLGA microspheres. By analyzing the experimental data using the soft-particle
      theory, it was indicated that the microspheres became 'softer' and the surface
      charge density of microspheres increases by the degradation. On the other hand,
      the surface of PLGA microspheres became harder and the electric charge density
      increased by the adsorption of pulmonary surfactant on the surfaces of PLGA
      microspheres. The changes in the surface charge density with degradation became
      larger by the adsorption of the lung surfactant on PLGA microsphere surfaces. It
      is considered that the changes in surface properties of PLGA microspheres affect
      their uptake efficiency by alveolar macrophage.

PMID- 17197162
TI  - Magnesium intake, glucose and insulin serum levels in pre-school very-low-birth
      weight pre-term children.
AB  - AIMS: To evaluate cross-sectional associations between dietary magnesium intake
      and the metabolic pattern of very-low-birth-weight (VLBW, <1500 g) pre-term
      children, in pre-school years (>2 and <6 years). METHODS AND RESULTS: Fifty-eight
      Italian children without major congenital malformations/conditions were enrolled;
      dietary intakes, clinical and (in 34 cases) laboratory characteristics were
      evaluated. Subjects with lower magnesium intake showed significantly higher
      fasting glucose, insulin and Homeostasis Model Assessment-Insulin Resistance
      (HOMA-IR) levels. At simple regression analysis, fasting glucose was
      significantly associated with magnesium intake (inversely) and catch-up growth
      (CUG). Fasting insulin and HOMA-IR values were inversely associated with intakes
      of magnesium and fibres, and directly with Body Mass Index (BMI) and CUG. In a
      multiple regression model, after adjusting for multiple confounders and fibre
      intake, magnesium intake was inversely associated with glucose (beta=-0.018;
      95%CI -0.026 to -0.010), but not with insulin or HOMA-IR levels. In the same
      model, dietary fibres remained inversely associated with insulin (beta=-0.075; 
      0.14 to -0.008) and HOMA-IR levels (beta=-0.06; -0.11 to -0.01). CONCLUSION:
      These results suggest a significant association between reduced magnesium intake
      and fasting glucose, and between reduced fibre intake and insulin resistance and
      this is present even in earlier childhood, and independently of BMI and growth
      characteristics.

PMID- 17197164
TI  - Implications of chronic obstructive pulmonary disease (COPD) on patients' health
      status: a western view.
AB  - AIM: To assess and compare health status among chronic obstructive pulmonary
      disease (COPD) patients presenting for treatment in six countries and in two
      healthcare settings using a generic health status instrument. METHODS: A
      population based cross-sectional survey was conducted among 2703 patients and
      their physicians (1381 in primary and 1322 in specialty care) in five EU
      countries and the USA. Information was collected on demographic and clinical
      characteristics, exacerbations and health status estimated using EQ-5D. RESULTS:
      The mean EQ-5D score for COPD patients was similar between primary and specialty
      settings in all countries except Italy. Approximately, half of the patients
      indicated some impairment in health status on mobility, usual activities,
      pain/discomfort and anxiety/depression domains of EQ-5D. Approximately, 5% of
      patients in EU countries except UK had health status valued as worse than death
      based on valuations of the general population. Patients suffering from severe
      breathlessness, experiencing > or =3 exacerbations in the previous year,
      categorised as severe according to GOLD criteria, and experiencing day-time and
      night-time symptoms had significantly impaired health status. CONCLUSION: COPD
      patients classified as moderate/severe in clinical practice have worse health
      status compared to mild patients. This impairment is similar in primary and
      specialty setting across western countries.

PMID- 17197163
TI  - Biomarkers of oxidative stress in schizophrenic and control subjects.
AB  - Increasing evidence indicates that oxidative injury exists in schizophrenia.
      Although it may not be the main cause, oxidative damage has been suggested to
      contribute to the pathophysiology and may account for deteriorating course and
      poor outcome in schizophrenia. A human study was undertaken, therefore, to
      investigate possible differences in biomarkers of DNA, lipid and protein
      oxidation in schizophrenic (n=16) and control subjects (n=17). Plasma vitamin C
      levels were also compared in both groups. Cellular DNA damage and plasma protein
      carbonyl levels were increased in the schizophrenic group compared to control
      subjects but not significantly. However, DNA damage in lymphocytes from the male
      schizophrenic group was significantly higher than the female group. Biomarkers of
      lipid peroxidation and plasma vitamin C levels also revealed no significant
      difference between the two groups under investigation, although a significant
      elevation in plasma vitamin C was observed in the female control group when
      compared to the male groups.

PMID- 17197165
TI  - Evaluation of methods for sorting CCA-treated wood.
AB  - Construction and demolition (C&D) wood frequently contains treated wood including
      wood treated with chromated copper arsenate (CCA). Many recycling options for
      such wood require that the product be essentially free of preservative chemicals.
      The objectives of this study were to document the characteristics of the wood
      waste stream and to evaluate the effectiveness of sorting methods for identifying
      treated wood. Sorting methods evaluated included visual sorting and visual
      sorting augmented with the use of PAN indicator stain and/or hand-held X-ray
      fluorescence (XRF) units. Experiments were conducted on two types of construction
      and demolition (C&D) wood: source separated loads containing only C&D wood and
      wood hand-picked from commingled loads of general C&D waste. Results showed that
      77% of the treated wood was CCA-treated. For uncontaminated piles (<1% treated
      wood) of source separated C&D wood, visual sorting was found to effectively
      remove the small amounts of treated wood present. For piles of source separated
      wood that were contaminated (approximately 50% treated wood), visual sorts were
      not accurate and benefited from augmented sorting using PAN indicator stain. The
      handheld XRF devices were found to be effective for sorting commingled C&D wood,
      as PAN indicator stain was not as effective due to the excessive amount of
      surface dirt associated with commingled wood waste. Visual sorting of source
      separated wood was estimated to cost between US$21 to US$96 per metric ton. These
      costs depended upon the amount of treated wood and whether or not augmentation
      with PAN indicator was necessary. Visual sorting augmented with hand-held XRF
      units was estimated at US$113 per metric ton. The bulk of these costs were
      associated with labor. Future efforts should focus on reducing labor costs by
      mounting automated XRF units on conveyor systems.

PMID- 17197166
TI  - Determination of Vitamin D-dependent calcium absorption by 45Ca gavage in the
      rat.
AB  - Precise determination of Vitamin D-dependent intestinal calcium absorption in
      longitudinal studies is problematic. We have assessed Vitamin D-dependent
      intestinal calcium absorption by (45)Ca gavage. Rats were gavaged with a 1mL
      solution containing (45)Ca (CaCl(2), 9.3MBq/mL) maintained at 37 degrees C. Total
      Ca concentration of the gavage fluid was optimised by comparing the absorption
      curves for fluids made up to 0.025, 2.025, 4.025 and 40.025 mmol/L with
      (40)CaCl(2). The effect of varying dietary Ca on fractional Ca absorption was
      determined in rats fed semi-synthetic diets containing either 0.05%, 0.2%, 0.4%
      or 1.0% Ca for 50 days. Serum 1,25 dihydroxyvitamin D (1,25D) was determined by
      radioimmunoassay. Total gavage Ca of 0.025 mmol/L achieved the highest peak
      fractional absorption and was adopted for all future experiments. Fifty days
      after allocation to the diets both fractional Ca absorption and 1,25D were
      highest in rats fed 0.05% Ca and lowest in those fed 1.0% Ca (absorption, P<0.05
      and 1,25D, P<0.05). There was a strong logarithmic relationship between 1,25D and
      fractional Ca absorption (R(2) 0.69, P<0.001). Weekly repetition of the procedure
      did not cause a fall in haematocrit over 7 weeks. Radiocalcium ((45)Ca)
      absorption by gavage provides a simple measure of Vitamin D-dependent Ca
      absorption for repetitive use in longitudinal studies.

PMID- 17197167
TI  - The anomalous behaviour of exogenous 25-hydroxyvitamin D in competitive binding
      assays.
AB  - The Vitamin D International External Quality Assessment Scheme (DEQAS) was
      established in 1989 to monitor the performance of assays for 25-hydroxyvitamin D
      (25-OHD) and 1,25-dihydroxyvitamin D (I,25(OH)(2)D). This is achieved through the
      quarterly distribution of five samples of human serum. Results are used to
      calculate an All-Laboratory Trimmed Mean and a Method Mean for each of the
      methods used by participants. In July 2005, participants were asked to assay
      serum to which 50.9 nmol of either 25-OHD(3) or 25-OHD(2) had been added as
      ethanolic solutions. The final concentration of ethanol in the serum was 0.7%.
      The distribution also included a sample of the original serum (OS) containing
      0.7% pure ethanol. The percentage recoveries of exogenous 25-OHD(3) (R1) and 25
      OHD(2) (R2) were calculated for each method. Results (OS nM, R1 and R2) were as
      follows: DiaSorin RIA (n=53); 39.2, 82.1%, 83.3%, DiaSorin Liason (n=16); 36.8,
      81.4%, 88.6%, IDS RIA (n=21); 36.4, 54.2%, 29.1%, IDS OCTEIA (n=16); 47.3, 78.8%,
      56.4%, Nichols Advantage (n=21); 58.9, 46.4%, 43.2%, HPLC (n=9); 42.6, 112.2%,
      97.1%, LC-MS (n=4); 34.0, 111.5%, 118.1%. The IDS RIA and Nichols assays gave
      unexpectedly low recoveries. This does not appear to be a calibration problem or
      the effect of ethanol.

PMID- 17197168
TI  - Multiple enhancer regions located at significant distances upstream of the
      transcriptional start site mediate RANKL gene expression in response to 1,25
      dihydroxyvitamin D3.
AB  - One of the primary regulators of receptor activator of NF-kappaB ligand (RANKL)
      is 1,25-dihydoxyvitamin D(3) (1,25(OH)(2)D(3)). To elucidate the mechanism
      whereby 1,25(OH)(2)D(3) activates RANKL expression we screened some 300kb of the
      RANKL gene locus using a ChIP on chip analysis and identified five potential
      regulatory regions lying significant distances upstream of the transcription
      start site (TSS), the farthest over 70kb from the TSS. A direct ChIP analysis
      confirmed the presence of the VDR/RXR heterodimer at these sites. The binding of
      the VDR was associated with histone modification and enhanced entry of RNA
      polymerase II, indicating an important functional consequence to the localization
      of these transcription factors in response to 1,25(OH)(2)D(3). The region -76kb
      upstream from the TSS, termed D5, was capable of mediating VDR-dependent
      transcriptional output in response to 1,25(OH)(2)D(3) in luciferase assays. The
      identified VDRE in this region was able to confer dramatic 1,25(OH)(2)D(3)
      sensitivity to heterologous promoters. This region was highly evolutionarily
      conserved and functionally active in the human RANKL gene as well. We propose
      that the RANKL gene is regulated via multiple enhancers that while located at
      significant distances from the TSS, likely form a chromatin hub centered on the
      RankL promoter.

PMID- 17197170
TI  - Observations from the UK Supra-Regional Assay Service laboratory for the
      measurement of Vitamin D metabolites.
AB  - As a Supra-Regional Assay Service (SAS) laboratory, we receive samples from all
      over the UK. Of these some are sent frozen and others by post or courier. We have
      examined transport and storage conditions to see whether they affect the
      measurement of Vitamin D metabolites and potentially contribute to the variation
      in measurement of 25-hydroxyvitamin D (25OHD) seen in the DEQAS scheme. We have
      also examined the samples received during 2005. We found that different transport
      and storage conditions did not contribute significantly to the normal variation
      seen in measuring Vitamin D metabolites (CV% (+/-S.E.) for stored versus assay
      controls: 5.1+/-0.06% versus 4.5+/-0.04% for 25OHD and 10.8+/-1.0% versus 12.3+/
      1.0% for 1,25D). A review of the service showed a 240% increase in samples
      received over the last 5 years. Despite an increased awareness of the need to
      measure Vitamin D status, in this cross-section of patient samples 92% of Asian
      and 86% of white patients were found to be Vitamin D-insufficient (<30 ng/ml) and
      27% of Asian and 14% of white patients were profoundly deficient (<5 ng/ml) and
      at risk of bone disease.

PMID- 17197169
TI  - Vitamin D in patients with renal failure: a summary of observational mortality
      studies and steps moving forward.
AB  - Although approximately half of patients undergoing hemodialysis receive activated
      forms of Vitamin D, the primary reason to initiate this therapy has rested solely
      on the management of secondary hyperparathyroidism. Secondary hyperparathyroidism
      is likely one of several consequences of Vitamin D deficiency, and only now have
      other consequences of Vitamin D deficiency emerged. Although previously viewed as
      a contributor to hypercalcemia and hyperphosphatemia, recent studies suggest
      Vitamin D may improve cardiovascular structure and function, improve vascular
      compliance, and reduce pro-inflammatory cytokines, all of which may contribute to
      the improved survival observed in retrospective studies examining the outcome of
      patients treated with activated Vitamin D compared to those who were not. The
      current review examines two recent large-scale studies of hemodialysis patients:
      one that demonstrated a survival advantage of paricalcitol over calcitriol, and a
      second that demonstrated a significant survival advantage of any intravenous
      Vitamin D formulation versus none. In both studies, the findings were independent
      of mineral and parathyroid hormone levels, suggesting "non-traditional" actions
      of Vitamin D contributed to the observed survival advantage. Potential steps
      moving forward in light of these observational studies are subsequently
      discussed.

PMID- 17197171
TI  - Estrogen promotes reversible epithelial-to-mesenchymal-like transition and
      collective motility in MCF-7 breast cancer cells.
AB  - The role of estrogen in the motility and invasion of breast cancer cells is
      controversial. Although estrogen receptor (ER)-positive breast tumors are
      considered less aggressive and more differentiated they still undergo metastasis.
      In many types of epithelial cancers, the ability to undergo metastasis has been
      associated with a loss of epithelial features and acquisition of mesenchymal
      properties leading to migration of individual cells, a process known as
      epithelial-to-mesenchymal transition (EMT). In this report, we show that a subset
      of ER-positive breast cancer cells can acquire mesenchymal-like features and
      motility in a reversible manner. In MCF-7 breast cancer cells estrogen-promoted
      acquisition of mesenchymal-like features while antiestrogens, such as tamoxifen,
      prevented this transition. Moreover, pharmacological inhibition of Src family
      kinases decreased the ability of estrogen to promote epithelial-to-mesenchymal
      like transition. In addition to mesenchymal-like motility, a subset of estrogen
      treated cells also moved as cell clusters (collective motility). While membrane
      localization of E-cadherin/beta-catenin was decreased in fibroblast-like cells,
      enhanced levels of E-cadherin/beta-catenin were detected in motile cell clusters.
      Thus, during tumor progression, estrogen may foster motility and invasion of ER
      positive breast cancer by promoting simultaneously reversible EMT-like changes
      and collective motility. These studies suggest that antiestrogen therapy and Src
      family kinase inhibitors may decrease development of metastases in ER-positive
      breast cancer by blocking estrogen-dependent migration of human breast cancer
      cells.

PMID- 17197172
TI  - Activation of MAPKs by 1alpha,25(OH)2-Vitamin D3 and 17beta-estradiol in skeletal
      muscle cells leads to phosphorylation of Elk-1 and CREB transcription factors.
AB  - The mitogen activated protein kinases (MAPKs) have been classified into at least
      six subfamilies, among which ERK1/2, JNK1/2 and p38 MAPK are the most extensively
      studied. The steroid hormones 1alpha,25-dihydroxy-Vitamin D(3) and 17beta
      estradiol promote biological responses through activation of MAPK cascades in
      various cell types. We previously reported that 1alpha,25(OH)(2)D(3) rapidly
      (within 1 min) activates p38 MAPK in C2C12 skeletal muscle cells. In this work,
      using the same muscle cell line, we demonstrate that 1alpha,25(OH)(2)D(3) or
      17beta-estradiol phosphorylate and activate ERK1/2 and p38 MAPK after longer
      treatment intervals, maximal effects seen at 90 and 30 min (ERK1/2) and at 60 and
      15 min (p38 MAPK) for these hormones, respectively. Hormone-dependent ERK and p38
      activation was abolished by MAPK specific inhibitors U0126 and SB203580.
      1alpha,25(OH)(2)D(3) and 17beta-estradiol also induced the phosphorylation of
      CREB and Elk-1 transcription factors in an ERK1/2-dependent manner. Simultaneous
      addition of both hormones potentiated CREB phosphorylation. 1alpha,25(OH)(2)D(3)-
      and 17beta-estradiol-induced c-fos expression, which was mediated by p38
      phosphorylation. The action of 17beta-estradiol on c-fos levels was also
      dependent on ERK1/2. These results suggest that MAPK signalling pathways play an
      important role in regulating early gene expression through CREB and Elk-1
      activation in skeletal muscle cells.

PMID- 17197173
TI  - The assessment of circulating 25(OH)D and 1,25(OH)2D: where we are and where we
      are going.
AB  - The field of Vitamin D assay technology has progressed significantly over the
      past 4 decades. Further, the clinical utility of these measurements has moved
      from esoteric into mainstream clinical diagnosis. This movement has been fueled
      by the realization that Vitamin D is involved in bodily systems beyond skeletal
      integrity. The clinical assay techniques for circulating 25(OH)D and 1,25(OH)(2)D
      have progressed away from competitive protein binding assay (CPBAs) that utilize
      tritium reporters to radioimmunoassay (RIAs) that utilize both I(125) and
      chemiluminescent reporters. These advances have allowed direct serum analysis of
      25(OH)D in an automated format that provides a huge sample throughput. Detection
      of circulating 25(OH)D can also be achieved utilizing direct high-performance
      liquid chromatographic (HPLC) or liquid chromatography coupled with mass
      spectrometry (LC-MS) techniques. These methods are accurate, however, they
      require expensive equipment and restrict sample throughput in the large clinical
      laboratory. Direct serum detection of 1,25(OH)(2)D is unlikely to occur for many
      reasons as a sample pre-purification will always be required. However, a semi
      automated chemiluminescent detection system with automated sample preparation is
      in final development for the determination of circulating 1,25(OH)(2)D. These
      advances will allow both 25(OH)D and 1,25(OH)(2)D to be detected in an accurate,
      rapid fashion to meet the clinical demands we see emerging.

PMID- 17197174
TI  - Peripheral-type benzodiazepine receptor (PBR) aggregation and absence of
      steroidogenic acute regulatory protein (StAR)/PBR association in the
      mitochondrial membrane as determined by bioluminescence resonance energy transfer
      (BRET).
AB  - The steroidogenic acute regulatory protein (StAR) is responsible for acute
      control of cholesterol transport across the mitochondrial membrane, however the
      mechanism of StAR-associated cholesterol transport is unknown and may involve the
      peripheral-type benzodiazepine receptor (PBR)/endozepine system. Several
      molecules of PBR may associate to form a channel through which cholesterol passes
      to the inner mitochondrial membrane, and endozepine is the natural ligand for
      PBR. Bioluminescence resonance energy transfer (BRET) was used to test
      StAR/PBR/endozepine interactions, PBR aggregation, and the effect of second
      messengers on interactions. There was no evidence of StAR/PBR, StAR/endozepine,
      or PBR/endozepine interactions. The StAR and PBR fusion proteins were trafficking
      to the mitochondria as expected, but the endozepine fusion protein was not
      localized to the mitochondria indicating that it was not biologically active.
      Data were obtained indicating that PBR forms aggregates in the mitochondrial
      membrane. Energy transfer between PBR fusion proteins was dose and time
      dependent, but there was no effect induced by PK11195 ligand binding or
      pharmacologic activation of PKA or PKC second messenger pathways. It appears that
      PBR aggregates in the mitochondrial membrane, however there was no evidence that
      PBR aggregation is regulated in the acute control of steroidogenesis, or that PBR
      and StAR interact.

PMID- 17197175
TI  - Evolution of the fulvic acid fractions during co-composting of olive oil mill
      wastewater sludge and tree cuttings.
AB  - Fulvic acids (FAs) were isolated by a conventional procedure from two mixtures of
      the sludge residue obtained from olive oil mill wastewater (OMW) evaporated in
      open-air pond and tree cuttings (TC) at different stages of the co-composting
      process. The FAs were analyzed for elemental (C, H, N, S, O) and acidic
      functional group (carboxylic and phenolic) composition, and by
      ultraviolet/visible, Fourier transform infrared and fluorescence spectroscopies.
      At the initial stage of composting, FAs from the OMW sludge-TC mixtures were
      characterized by a prevalent aliphatic character, large contents of C, S
      containing groups, proteinaceous materials and polysaccharide components,
      extended molecular heterogeneity, small O and acidic functional group contents,
      and small degrees of aromatic ring polycondensation, polymerization and
      humification. As composting proceeded, C, H and S contents, C/N ratio, and
      aliphaticity decreased, whereas N, O, COOH and phenolic OH contents, C/H and O/C
      ratios, and aromaticity increased. These results suggested that, with increasing
      the composting time, the chemical and structural properties of the FA components
      of the two OMW sludge-TC mixtures approached the characteristics typical of
      native soil FAs. Thus, co-composting of OMW sludge mixed with TC may represent a
      suitable treatment for enhancing the quality of organic matter in these materials
      when used as soil amendments.

PMID- 17197176
TI  - Propionic acid accumulation and degradation during restart of a full-scale
      anaerobic biowaste digester.
AB  - The methane formation rate of 300 m(3) of sludge from a full scale biowaste
      reactor, that was stored without feeding for six weeks during a maintenance
      period, was about 60% of the methanogenic activity before maintenance. The 300
      m(3) sludge was then pumped back into the biowaste reactor. On the third day,
      after refilling of the stored biowaste suspension, anaerobic conditions were
      obtained and feeding was started by addition of 36.1 m(3) of fresh biowaste
      suspension (=11.3 tons biowaste). The pH dropped from originally pH 7.7 to pH 7.3
      and later on to pH 6.8, which was considered the minimum allowed pH for
      methanogenesis to recover. Maximum concentrations of acetate (1.78 gl(-1)), n
      butyrate (0.57 gl(-1)) and n-valerate (0.44 gl(-1)) accumulated during the
      following days with feeding of 11.8 tons on day 5 and twice 6.5 tons on days 7
      and 9, respectively. Thereafter, acetate, n-butyrate and n-valerate were degraded
      completely, whereas the concentration of propionate was still increasing.
      Propionic acid was the dominant fatty acid during the restart period and reached
      its maximum concentration of 6.2 gl(-1) 17 days after start of feeding. This high
      level of propionate was degraded completely in about 5 days with maximum
      degradation rates of 2.14 gl(-1)d(-1), and the pH of the anaerobic sludge
      increased from 7.1 to 7.4. During restart, the methane content of the biogas
      increased successively to 65%. Samples that were taken at different time
      intervals during the restart phase of the methane reactor showed different fatty
      acid degradation capabilities. After 10 days, when acetate and n-butyrate still
      accumulated in the methane reactor the maximum acetate degradation rate was 1.52
      gl(-1)d(-1) and the n-butyrate degradation rate was 0.51 gl(-1)d(-1). Oxidation
      of n-valerate caused an increase of propionate, which was degraded after a lag
      phase of 6 days with a maximum rate of 0.6 gl(-1)d(-1). In the samples taken
      after 16 and 23 days, the propionate degradation rate increased to 1.42 gl(-1)d(
      1) and 1.55 gl(-1)d(-1), respectively, and the lag phase for propionate
      degradation was reduced or had disappeared completely. The maximum propionate
      degradation rate was measured in the methane reactor in the fourth week after
      restart. The synthrophic propionate oxidizing bacteria were apparently the most
      suffering bacteria during sludge storage. If the propionate oxidizing bacteria
      could be kept active and the propionate degrading activity of the biowaste
      suspension of 6.16 gl(-1)d(-1) before the maintenance period could be maintained,
      then accumulation of 6.2 gl(-1) propionate in the methane reactor after restart
      could be avoided and full activity reached even earlier.

PMID- 17197177
TI  - Synthesis and biological evaluation of 4-amino derivatives of
      benzimidazoquinoxaline, benzimidazoquinoline, and benzopyrazoloquinazoline as
      potent IKK inhibitors.
AB  - We have recently identified BMS-345541 (1) as a highly selective and potent
      inhibitor of IKK-2 (IC50 = 0.30 microM), which however was considerably less
      potent against IKK-1 (IC50 = 4.0 microM). In order to further explore the SAR
      around the imidazoquinoxaline tricyclic structure of 1, we prepared a series of
      tetracyclic analogues (7, 13, and 18). The synthesis and biological activities of
      these potent IKK inhibitors are described.

PMID- 17197178
TI  - Novel pyridinyl and pyrimidinylcarbazole sulfonamides as antiproliferative
      agents.
AB  - A series of azaheterocyclic carbazole sulfonamides was synthesized and evaluated
      for antiproliferative activity. The most potent compounds N-(2,6
      dimethoxypyridine-3-yl)-9-ethyl and 9-methylcarbazole-3-sulfonamide (13 and 14)
      gave significant cytotoxicity (IC50 = 122 and 101 nM). Compound 13 displayed
      submicromolar activities against seven human tumor cell lines. The SARs of this
      series of sulfonamides which includes the influence of azaheterocycle rings,
      sulfonamide linkage, and the carbazole ring are described.

PMID- 17197179
TI  - Antihyperglycemic and antidyslipidemic agent from Aegle marmelos.
AB  - The plant Aegle marmelos belongs to the family of Rutaceae. From the leaves of A.
      marmelos an alkaloidal-amide, Aegeline 2, was isolated and found to have
      antihyperglycemic activity as evidenced by lowering the blood glucose levels by
      12.9% and 16.9% at 5 and 24h, respectively, in sucrose challenged streptozotocin
      induced diabetic rats (STZ-S) model at the dose of 100mg/kg body weight. Aegeline
      2 has also significantly decreased the plasma triglyceride (Tg) levels by 55%
      (P<0.001), total cholesterol (TC) by 24% (P<0.05), and free fatty acids (FFA) by
      24%, accompanied with increase in HDL-C by 28% and HDL-C/TC ratio by 66% in
      dyslipidemic hamster model at the dose of 50mg/kg body weight. The reasonable
      mapping of compound 2 to validated pharmacophoric hypothesis and 3D QSAR model
      with an estimated activity (283nM) suggest that the compound 2 might be a beta(3)
      AR agonist.

PMID- 17197180
TI  - The evaluation and structure-activity relationships of 2-benzoylaminobenzoic
      esters and their analogues as anti-inflammatory and anti-platelet aggregation
      agents.
AB  - Forty-seven 2-benzoylaminobenzoic esters were synthesized and evaluated in anti
      platelet aggregation, inhibition of superoxide anion generation, and inhibition
      of neutrophil elastase release assays. Most 2-benzoylamino-4-chlorobenzoic acid
      derivatives showed selective inhibitory effects on arachidonic acid (AA)-induced
      platelet aggregation. Among them, compounds 6b and 7b exhibited more potent
      inhibitory effects (ca. 200-fold) than aspirin. Additionally, compounds 1a and 5a
      showed strong inhibitory effects on neutrophil superoxide generation with IC(50)
      values of 0.65 and 0.17 microM, respectively. However, compounds 6d and 6e
      exhibited dual inhibitory effects on platelet aggregation and neutrophil elastase
      (NE) release; therefore, these two compounds may be new leads for development as
      anti-inflammatory and anti-platelet aggregatory agents.

PMID- 17197181
TI  - Synthesis of potent and tissue-selective androgen receptor modulators (SARMs): 2
      (2,2,2)-Trifluoroethyl-benzimidazole scaffold.
AB  - The synthesis and in vivo SAR of 2-(2,2,2)-trifluoroethyl-benzimidazoles are
      described. Prostate antagonism and/or levator ani agonism can be modulated by
      varying the substitution at the 2-position of 5,6-dichloro-benzimidazoles. Potent
      androgen agonists on the muscle were discovered that strongly bind to the
      androgen receptor (2-17 nM) and show potent in vivo efficacy (0.03-0.11 mg/day).
      True SARMs showing both prostate antagonism and levator ani agonism were
      revealed.

PMID- 17197182
TI  - High-throughput screening affords novel and selective trypanothione reductase
      inhibitors with anti-trypanosomal activity.
AB  - Trypanothione reductase (TR), an enzyme that buffers oxidative stress in
      trypanosomatid parasites, was screened against commercial libraries containing
      approximately 134,500 compounds. After secondary screening, four chemotypes were
      identified as screening positives with selectivity for TR over human glutathione
      reductase. Thirteen compounds from these four chemotypes were purchased, and
      their in vitro activity against TR and Trypanosoma brucei is described.

PMID- 17197183
TI  - Synthesis of O-prenylated and O-geranylated derivatives of 5-benzylidene2,4
      thiazolidinediones and evaluation of their free radical scavenging activity as
      well as effect on some phase II antioxidant/detoxifying enzymes.
AB  - A series of 5-arylidene-2,4-thiazolidinediones and its geranyloxy or prenyloxy
      derivative were synthesized and studied for their radical scavenging activity
      using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Their comparable scavenging
      activities were expressed as IC50 value. Compounds 2c, 2d, 4d, and 6a showed
      appreciable radical scavenging activities. The vanillin based thiazolidinedione
      compound 2c displayed highest activity comparable to that of alpha-tocopherol.
      But in vivo, compound 6a showed better results in inducing phase II
      detoxifying/antioxidative enzyme.

PMID- 17197184
TI  - Chromosome organization: new facts, new models.
AB  - The study of nuclear organization has radically changed the way we envision gene
      regulation, imposing a paradigm shift from a seemingly featureless nucleus to a
      highly compartmentalized and complex organelle. The positioning of genes,
      regulatory sequences and transcription factors in relation to each other and to
      landmarks in the nucleus, such as nuclear bodies and the lamina, is important in
      determining which genes are transcribed at any one time. Investigating chromatin
      organization during interphase is therefore essential to the understanding of
      gene expression. The recent discovery of interactions between distal chromatin
      segments that occur within the same chromosome or across different chromosomes,
      and that have a role in transcription regulation, suggests a re-evaluation of
      current models of chromosome organization and the development of new ones.

PMID- 17197185
TI  - Repression of protein synthesis by miRNAs: how many mechanisms?
AB  - MicroRNAs are approximately 21-nucleotide-long regulators of gene expression that
      gain access to their target mRNAs by complementary base pairing. Recent studies
      have revealed that animal microRNAs might take diverse routes to repress gene
      expression, affecting both target mRNA levels and translation. Mechanistic
      details of microRNA-mediated repression are starting to emerge but a
      comprehensive picture of the inhibition, and particularly the effects on mRNA
      translation, is still lacking. Recent data support different microRNA mechanisms
      and a role for cytoplasmic processing bodies in the degradation and storage of
      mRNAs targeted by microRNA regulators.

PMID- 17197186
TI  - Comparison of standing balance between female collegiate dancers and soccer
      players.
AB  - STUDY DESIGN: This study was designed as a comparison study of two cohorts.
      OBJECTIVES: The hypothesis of this study was that soccer players and dancers have
      different balance abilities and that these differences could be objectively
      measured using center of pressure measurements. BACKGROUND: Center of pressure
      (COP) measurements are reproducible and have been validated in the literature for
      assessing standing balance. The literature does not provide sensitive enough
      techniques for discriminating between two groups of athletes with excellent
      standing balance. METHODS AND MEASURES: A Matscan pressure mat (Tekscan, Boston,
      MA) was used to compare COP change variability between 32 female collegiate
      soccer players and 32 dancers. COP was used to calculate sway index, center
      acquisition time, sway path length and sway velocity as measures of standing
      balance. RESULTS: The dancers had significantly better balance scores (p<0.05) in
      5 of 20 balance tests. Results for the remaining 15 balance tests were not
      significantly different. CONCLUSION: These data show that standing balance
      characteristics of dancers and soccer players can be objectively measured using
      COP data. Dancers have certain standing balance abilities that are better than
      those of soccer players. The COP measurements in this study can be used as a tool
      in future studies investigating standing balance in different groups of athletes.

PMID- 17197188
TI  - 4-amino-5-aryl-6-arylethynylpyrimidines: structure-activity relationships of non
      nucleoside adenosine kinase inhibitors.
AB  - A series of non-nucleoside adenosine kinase (AK) inhibitors is reported. These
      inhibitors originated from the modification of 5-(3-bromophenyl)-7-(6-morpholin-4
      ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine (ABT-702). The identification of
      a linker that would approximate the spatial arrangement found between the
      pyrimidine ring and the aryl group at C(7) in ABT-702 was a key element in this
      modification. A search of potential linkers led to the discovery of an acetylene
      moiety as a suitable scaffold. It was hypothesized that the aryl acetylenes, ABT
      702, and adenosine bound to the active site of AK (closed form) in a similar
      manner with respect to the orientation of the heterocyclic base. Although potent
      acetylene analogs were discovered based on this assumption, an X-ray crystal
      structure of 5-(4-dimethylaminophenyl)-6-(6-morpholin-4-ylpyridin-3
      ylethynyl)pyrimidin-4-ylamine (16a) revealed a binding orientation contrary to
      adenosine. In addition, this compound bound tightly to a unique open conformation
      of AK. The structure-activity relationships and unique ligand orientation and
      protein conformation are discussed.

PMID- 17197187
TI  - Synthesis and cytotoxic evaluation of C-9 oxidized podophyllotoxin derivatives.
AB  - A series of podophyllotoxin and podophyllic aldehyde derivatives, lacking the
      lactone ring and oxidized at C-9 position, has been prepared. The functionalities
      considered at C-9 were carboxylic acids and several derivatives such as esters,
      amides, nitriles or anhydrides. The synthesized compounds were cytotoxic at the
      micromolar level, though less potent and selective than the parent compounds,
      revealing the influence of the C-9 electrophilic character on the potency and
      selectivity of these cyclolignans.

PMID- 17197189
TI  - Lactotriaose-containing carbosilane dendrimers: syntheses and lectin-binding
      activities.
AB  - Carbosilane dendrimers periphery-functionalized with lactotriaose (GlcNAcbeta1
      3Galbeta1-4Glc) with valencies of three, four, six, and twelve were prepared for
      use in a lectin-binding assay. A lactotriaose derivative was prepared from D
      glucosamine and D-lactose derivatives. The N-Troc-protected glucosamine glycosyl
      donor and 3'-O-unprotected lactose glycosyl acceptor were condensed in the
      presence of silver trifluoromethanesulfonate and methylsulfenyl bromide to
      provide corresponding trisaccharide with new beta-1-3 linkages in 92% yield. The
      protection group of the trisaccharide was transformed into an acetyl group. The 4
      pentenyl glycoside was prepared from the acetate via glycosyl bromide. The alkene
      was converted into acetyl sulfide by addition of thioacetic acid under radical
      conditions. The lactotriaose unit was linked with carbosilane dendrimers to
      afford acetyl-protected glycodendrimers. De-O-acetylation of the dendrimers was
      carried out in the presence of sodium methoxide and then aq NaOH to give the
      desired lactotriaose clusters using a carbosilane dendrimer backbone. Their
      biological activities toward WGA were evaluated by fluorescence methods. The
      binding constants of free lactotriaose and trivalent, tetravalent, hexavalent,
      and dodecavalent glycodendrimers to WGA were determined to be 1.1x10(3),
      4.4x10(4), 5.1x10(4), 2.8x10(6), and 1.3x10(6) M-1, respectively. The hexavalent
      glycodendrimer showed a 2500-fold larger binding effect than that of free
      lactotriaose.

PMID- 17197190
TI  - EPO in cancer anemia: benefits and potential risks.
AB  - Anemia has an incidence both on the quality of life and the evolution of cancer.
      Anemia may result in cancer from either a bone marrow infiltration of cancer
      cells or a cytotoxic effect of chemotherapy and/or radiotherapy, or both. EPO is
      a glycoprotein which stimulates erythrocyte formation by bone marrow progenitory
      cells. Recombinant EPO has considerably improved treatment of anemic patients, by
      increasing hemoglobin serum levels and reducing the need for blood transfusion.
      The quality of life of cancer patients is thus improved and several studies
      highlight the beneficial role of EPO on the clinical outcome. A preclinical
      background and some clinical data suggest however a detrimental role of EPO in
      cancer by a possible stimulation of tumor growth. There is a need of more
      clinical trials in order to assess the effects of EPO on tumors and their
      treatment.

PMID- 17197191
TI  - Negligible influence of comorbidity on prognosis of patients with small cell lung
      cancer: a population-based study in the Netherlands.
AB  - Management of small cell lung cancer (SCLC) among elderly is complex because of
      decreased organ functions and interactions with comorbidity. Since elderly
      patients are often excluded from clinical trials, little is known about the way
      they are treated and outcome. We evaluated the prognostic effects of rising age
      and comorbidity in unselected Dutch SCLC patients (Eindhoven Cancer Registry).
      Elderly patients received chemotherapy less often and the dose was also reduced
      more often. Cardiovascular diseases, hypertension or diabetes lowered the
      proportion receiving combined chemotherapy and radiotherapy among patients with
      limited disease. About 80% of the patients receiving chemotherapy suffered from a
      side effect, which was not related to age. After adjustment for age, gender,
      stage and treatment modality, comorbidity had a negligible prognostic effect.
      Chemotherapy (in combination with radiotherapy) seemed to improve survival,
      however, toxicity and quality of life in these patients should be evaluated
      thoroughly in future randomized studies.

PMID- 17197192
TI  - Relevance, advantages and limitations of animal models used in the development of
      monoclonal antibodies for cancer treatment.
AB  - Antibody humanisation through recombinant DNA technology was a key step in
      allowing monoclonal antibodies (mAbs) to reach the clinic, particularly for the
      treatment of cancer. As a consequence, they are less adapted to animal studies,
      although these studies continue to be important tools to study antibody
      distribution and action at the level of a whole organism. Moreover, preclinical
      studies in animals are mandatory before the approval of biologics license
      applications for mAbs by the U.S. Food and Drug Administration (FDA) or European
      Agency for the Evaluation of Medicinal Products (EMEA). Different parameters
      should be taken in consideration before starting animal experiments with
      recombinant mAbs, including antibody cross-reactivity, immunogenicity,
      pharmacokinetics, and possible interactions with the host immune system. The
      various interspecies differences are reviewed and discussed in light of the
      pharmacological properties expected in patients. In doing so, this article aims
      to provide a critical review of the animal models used in preclinical studies of
      mAbs for cancer treatment. In particular, their relevance, advantages and
      limitations will be discussed.

PMID- 17197193
TI  - Cardiotrophin-1 induces interleukin-6 synthesis in human umbilical vein
      endothelial cells.
AB  - In patients with chronic heart failure (CHF) increased plasma concentrations of
      proinflammatory cytokines are found. For example, the plasma interleukin-6 (IL-6)
      concentration correlates with disease severity. Beside IL-6 cardiotrophin-1 (CT
      1), a member of the IL-6 superfamily, is also increased in CHF. We examined
      whether CT-1 is able to induce IL-6 in human umbilical vein endothelial cells
      (HUVEC) and characterised the underlying pathway. IL-6 mRNA was determined by
      real-time PCR and by RT-PCR in HUVEC which were stimulated with different CT-1
      concentrations and for different time periods. IL-6 concentration in the
      supernatant was determined by ELISA. For the pathway determination following
      inhibitors were used: piceatannol (signal transducer and activation of
      transcription (STAT)3 phosphorylation), wortmannin (phosphatiylinositol 3-kinase
      (PI3K)), SB203580 (p38 mitogen-activated protein kinase (MAPK)), AG490 (Janus
      kinase (JAK)2), PD98059 (mitogen-activated protein kinase kinase (MEK) 1/2),
      parthenolide (nuclear factor kappaB) and cycloheximide (protein biosynthesis). CT
      1 caused a concentration- and time-dependent increase in IL-6 mRNA in HUVEC with
      a maximal induction seen after 6 h (2-fold compared to control) with 100 ng/ml CT
      1. In the supernatant of HUVEC a concentration- and time-dependent increase of IL
      6 protein was found. A maximum effect with 100 ng/ml CT-1 was found after 24 h
      (11-fold compared to control). AG490, SB203580, piceatannol, parthenolide and
      cycloheximide inhibit CT-1 induced IL-6 mRNA and protein expression whereas
      wortmannin and PD98059 did not inhibit IL-6 expression. CT-1 induced both IL-6
      mRNA and protein in a concentration- and time-dependent manner in HUVEC. The
      underlying pathway includes activation of JAK2, STAT3, p38 and NFkappaB. CT-1
      induced IL-6 expression and requires protein synthesis and IL-6 is not stored
      intracellularly. We speculate that in CHF CT-1 might be in part responsible for
      increased IL-6 plasma concentrations. Modulation of the CT-1 pathway may be a
      further strategy in CHF treatment.

PMID- 17197195
TI  - Using Ciona to study developmental programmed cell death.
AB  - Ciona intestinalis, a member of Tunicates, the closest group to vertebrates, has
      emerged as an appropriate organism for the study of developmentally regulated
      programmed cell death. First, because massive phases of apoptosis occur all along
      embryogenesis. Second, because the lecithotrophic mode of development is
      associated with autophagic process occurring during juvenile formation. Third,
      because the biochemical cell death machinery is close to that found in mammals.
      Altogether, the Ciona system contributes to identify new specific regulatory
      pathways and to explain how molecular mechanisms of programmed cell death evolved
      from invertebrates to vertebrates.

PMID- 17197196
TI  - Programmed cell death in Hydra.
AB  - Hydra is one of the simplest metazoans and thus an important model organism for
      studies on the evolution of developmental mechanisms in multi-cellular animals.
      In Hydra apoptosis is involved in the regulation of cell numbers in response to
      feeding, in regeneration and in the removal of non-self cells. It also
      participates in the maintenance of cellular homeostasis in germ cells. During
      oogenesis a special "arrested" apoptosis of nurse cells is observed. The
      morphology of apoptotic hydra cells is almost indistinguishable from apoptosis in
      higher animals and caspases as well as members of the Bcl-2 family participate in
      the process.

PMID- 17197194
TI  - Differential regulation of IL-6 and TNF-alpha via calcineurin in human skeletal
      muscle cells.
AB  - Interleukin-6 increases in skeletal muscle during exercise, and evidence points
      to Ca2+ as an initiator of IL-6 production. However, the signalling pathway
      whereby this occurs is unknown. One candidate for Ca2+ -mediated IL-6 induction
      is calcineurin, an activator of NF-AT. Here we investigated whether skeletal
      myocytes produce IL-6 in a Ca2+/calcineurin-dependent manner, and whether TNF
      alpha, an inducer of IL-6, is affected by these stimuli. Human skeletal muscle
      cell cultures were stimulated with ionomycin time-and dose-dependently to elevate
      intracellular Ca2+ levels, with or without addition of cyclosporin A (CSA); a
      calcineurin inhibitor. mRNA was extracted from myocytes and analysed for IL-6 and
      TNF-alpha gene expression. IL-6 mRNA increased time- and dose-dependently with
      ionomycin stimulation, an effect that was blunted by approximately 75% in the
      presence of CSA. In contrast, TNF-alpha gene expression was decreased by
      approximately 70% in response to ionomycin treatment, but increased in response
      to addition of CSA. These data demonstrate that IL-6 and TNF-alpha are regulated
      differentially in skeletal muscle cells in response to a Ca2+ stimulus. Blocking
      the calcineurin pathway resulted in inhibition of the IL-6 response to ionomycin,
      whereas TNF-alpha increased by addition of CSA, further indicating a differential
      regulation of IL-6 and TNF-alpha in human skeletal myocytes.

PMID- 17197197
TI  - Distinct neuronal circuits mediate experience-dependent, non-associative
      osmotactic responses in Drosophila.
AB  - Osmotactic responses can be modified in an experience-dependent manner and have
      been used to condition animals in negative or positive associative paradigms.
      Experience-dependent non-associative defects in avoidance of aversive odors were
      reported in Drosophila learning mutants. This prompted an examination of the
      contribution of the mushroom bodies and inner antenoglomerular tract, the two
      neuronal populations implicated in processing olfactory information to experience
      dependent non-associative osmotactic responses. Silencing inner antenoglomerular
      tract synapses results in defective osmotaxis after experiencing a different
      odor, but not electric shock. Conversely, structural or functional perturbation
      of the mushroom bodies precipitates osmotactic deficits after prior experience of
      electric shock but not odors. These effects on osmotaxis are specific, long
      lasting and independent of the aversive or attractive properties of the odors.
      Deficient osmotactic responses only after electric shock stimulation were
      exhibited by mutants with altered cAMP levels, but all other mutants in genes
      preferentially expressed in the mushroom bodies responded normally. Our results
      suggest that the mushroom bodies and inner antenoglomerular tract are essential
      for normal osmotactic responses after prior stimulation with electric shock or
      another odor respectively. Finally, these experience-dependent non-associative
      paradigms are excellent methods of functionally ascertaining normal activity of
      the mushroom bodies and inner antenoglomerular tract in putative leaning and
      memory mutants.

PMID- 17197198
TI  - Multimodal fMRI tractography in normal subjects and in clinically recovered
      traumatic brain injury patients.
AB  - In this study, we defined an operator-independent protocol for reconstructing the
      anatomical connections originating from fMRI activations in order to demonstrate
      that results obtained with this protocol are affected by alterations of
      functional activations. Seven healthy volunteers and two patients who sustained
      traumatic brain injury underwent an fMRI with a finger tapping task and a DTI
      scan. Cortical fMRI activations were used directly as seed mask for tractography
      for the reconstruction of individual motor pathways. On patients we observed a
      different motor network if compared to healthy subjects. However, when the
      activations of healthy subjects were used as seed masks for the tractography in
      patients, we observed for the patients a pattern of connectivity more similar to
      what was observed for healthy subjects. At the same time, when the activations of
      patients were used for the tractography on healthy subjects, we obtained patterns
      of connectivity similar to those obtained for patients. These results show the
      potential of the integration of fMRI and tractography for clarifying the
      mechanisms of cortical plasticity in the recovery of motor functions.

PMID- 17197199
TI  - A nuclear phylogeny of the Florideophyceae (Rhodophyta) inferred from combined
      EF2, small subunit and large subunit ribosomal DNA: establishing the new red
      algal subclass Corallinophycidae.
AB  - Previous studies have indicated that resolution of supraordinal relationships in
      the red algal class Florideophyceae will require additional characters, improved
      taxon sampling and optimized methods of phylogenetic analysis. To this end, we
      have generated data to introduce a novel nuclear marker to red algal systematics,
      elongation factor 2, as well as expanded ribosomal DNA alignments (SSU and LSU)
      to include 62 ingroup and 4 outgroup taxa. Both single gene and combined data
      sets were considered. Our analyses resulted in better resolution of both deep as
      well as more recent divergences, with higher support realized at many nodes.
      Distance, parsimony and bayesian analyses of the single gene and combined data
      sets indicated that the subclasses Hildenbrandiophycidae, Ahnfeltiophycidae and
      Rhodymeniophycidae were monophyletic, whereas the Nemaliophycidae was
      polyphyletic: one lineage containing the Rhodogorgonales and Corallinales (CR
      complex); and the other containing the Acrochaetiales, Balbianiales, Balliales,
      Batrachospermales, Colaconematales, Nemaliales, Palmariales, and Thoreales (APB
      complex). Based on these results a new subclass of the Florideophyceae, the
      Corallinophycidae subclassis nov., is proposed to accommodate the Corallinales
      and Rhodogorgonales. In addition to resolving supraordinal relationships, the
      present analyses resolved some novel ordinal affinities within the
      Nemaliophycidae and Rhodymeniophycidae, which are discussed here.

PMID- 17197200
TI  - The ever-increasing diversity in mouse lemurs: three new species in north and
      northwestern Madagascar.
AB  - Mouse lemurs (Microcebus spp.) are the world's smallest primates and endemic to
      Madagascar. Several recent taxonomic revisions resulted in an extraordinary
      increase of recognized species. What still was considered as being two species at
      the beginning of the 20th century is currently recognized as 12 taxa. Based on
      fur coloration pattern, they can be divided into grayish and reddish forms. Two
      major models have been proposed to explain the extensive speciation events in the
      Malagasy fauna. The best known suggests that major rivers and mountains combine
      to act as effective barriers to gene flow and thereby facilitate allopatric
      speciation processes. A more recent model used an analysis of watersheds in the
      context of Quaternary climatic shifts to explain the process of explosive
      speciation on the island. We tested these two models by covering the areas
      between all major rivers (n=8) in northwestern and northern Madagascar. Mouse
      lemurs were systematically caught, sampled and morphometrically characterized in
      25 sites (with 2-49 individuals per site and species). A complete phylogeny was
      constructed on the basis of the sequences of three mitochondrial loci (in total
      1296 bp). The phylogenetic data revealed a previously unknown biodiversity with
      three new mouse lemur species among the reddish forms, each having a very small
      distribution, i.e., being restricted to only one Inter-River-System (IRS).
      Morphometric analyses underlined their distinctiveness and a brief formal species
      description is provided. In contrast to the reddish forms, grayish forms have a
      very low species diversity coupled with broad distributions that cover more than
      one IRS. These differences among the species are discussed as outcome of
      divergent colonization scenarios. Elements of both biogeographic models are
      combined in a new hypothesis that aims to explain the speciation process leading
      to the present distribution of mouse lemurs in Madagascar.

PMID- 17197201
TI  - Molecular phylogenetics and delimitation of species in Cortinarius section
      Calochroi (Basidiomycota, Agaricales) in Europe.
AB  - Cortinarius is the most species rich genus of mushroom forming fungi with an
      estimated 2000 spp. worldwide. However, species delimitation within the genus is
      often controversial. This is particularly true in the section Calochroi (incl.
      section Fulvi), where the number of accepted taxa in Europe ranges between c.60
      and c.170 according to different taxonomic schools. Here, we evaluated species
      delimitation within this taxonomically difficult group of species and estimated
      their phylogenetic relationships. Species were delimited by phylogenetic
      inference and by comparison of ITS sequence data in combination with
      morphological characters. A total of 421 ITS sequences were analyzed, including
      data from 53 type specimens. The phylogenetic relationships of the identified
      species were estimated by analyzing ITS data in combination with sequence data
      from the two largest subunits of RNA polymerase II (RPB1 and RPB2). Seventy-nine
      species were identified, which are believed to constitute the bulk of the
      diversity of this group in Europe. The delimitation of species based on ITS
      sequences is more consistent with a conservative morphological species concept
      for most groups. ITS sequence data from 30 of the 53 types were identical to
      other taxa, and most of these can be readily treated as synonyms. This emphasizes
      the importance of critical analysis of collections before describing new taxa.
      The phylogenetic separation of species was, in general, unambiguous and there is
      considerable potential for using ITS sequence data as a barcode for the group. A
      high level of homoplasy and phenotypic plasticity was observed for morphological
      and ecological characters. Whereas most species and several minor lineages can be
      recognized by morphological and ecological character states, these same states
      are poor indicators at higher levels.

PMID- 17197202
TI  - Phylogeny of parasitiform mites (Acari) based on rRNA.
AB  - Acari (mites and ticks) form one the most diverse lineages of arthropods, but
      basal relationships in the group are still poorly understood. The current study
      addresses this issue for one of its two main lineages, the order Parasitiformes.
      Relationships are examined at the subordinal and infraordinal level using
      complete 18S and partial 28S nuclear rRNA sequence data. Most currently
      recognized lineages are recovered with good support, suggesting that nuclear
      rRNA, and specifically 18S rRNA, is very well suited for analyzing relationships
      at this level in this lineage. These results were found despite quite variable
      rates of sequence evolution, with rates "ratcheting up" from relatively low in
      most non-mite arachnid lineages, to intermediate in Pseudoscorpiones, the mite
      order Acariformes, and the parasitiform suborders Opilioacarida, Holothyrida, and
      Ixodida, to high in the parasitiform suborder Mesostigmata. The most species rich
      mesostigmatid infraorder, Dermanyssina, shows huge distances to the outgroups,
      but remarkably low within-group divergence in nuclear rRNA. This suggests the
      possibility of a relatively recent origin of this lineage.

PMID- 17197203
TI  - Radial forearm free flap for reconstruction of the oral cavity: clinical
      experience in 55 cases.
AB  - OBJECTIVE: Since the advent of modern microvascular techniques, the radial
      forearm free flap (RFFF) has become a reliable method for reconstruction of
      defects within the oral cavity. The purpose of the present study was to evaluate
      our experience with the use of the RFFF for the reconstruction of oral cavity
      defects after tumor resection. STUDY DESIGN: During a 9-year period, 103
      consecutive patients were treated in our department for the reconstruction of
      oral defects after tumoral ablation by means of microvascularized free flaps.
      Fifty-five patients were reconstructed by means of the RFFF. Patients were
      treated for benign (n = 1) and malignant (n = 54) entities. All the patients
      underwent an abdominal split-thickness skin graft for the closure of the donor
      site. RESULTS: Fifty-five patients underwent reconstruction by means of the RFFF
      after resection of the oral cavity. Squamous cell carcinoma was present in 54
      patients. A mean age of 55.5 years was observed (range 16-78). Thirty-nine
      patients (70.9%) were men and 16 (29.1%) women. Primary reconstruction was
      achieved in 52 patients (96.3%). A fasciocutaneous graft was used in all of the
      cases, with a mean size of 7.39 x 5.17 cm. The mean flap ischemic time was 56.02
      minutes. During the immediate follow-up period, revision of the vascular
      anastomosis was necessary in 18.9% of the cases owing to flap ischemia.
      CONCLUSION: Our results revealed that the RFFF is a reliable method for
      reconstructing a wide range of oral cavity defects with an acceptable low
      morbidity rate. It provides adequate bulkiness and pliability, resulting in
      adequate reconstruction of a wide variety of defects within the oral cavity.

PMID- 17197204
TI  - Bisphosphonate-associated osteonecrosis of the jaws: a therapeutic dilemma.
AB  - OBJECTIVE: To describe our experience in prevention and treatment of mandibular
      and maxillary osteonecrosis, an emerging complication of long-term intravenous
      administration of bisphosphonates. STUDY DESIGN: Between February 2004 and
      February 2006, 10 patients who had received zoledronic acid intravenously because
      of multiple bone myelomas or bone metastases were treated for mandibular and
      maxillary osteonecrosis in the Departments of Otorhinolaryngology and
      Maxillofacial Surgery of our institution. RESULTS: All of the patients underwent
      surgical sequestrectomies. More extensive surgery was necessary in 3 cases. There
      were no major complications, and the majority of the patients are alive with no
      signs of infection or bone exposure. CONCLUSIONS: Our experience confirms that
      bisphosphonate therapy contributes to the pathogenesis of mandibular and
      maxillary osteonecrosis. Surgery seems to be necessary in the majority of the
      patients, although the most adequate procedure is far from being standardized and
      prevention seems to play a pivotal role.

PMID- 17197205
TI  - A swelling in the buccal mucosa with intracranial involvement.

PMID- 17197207
TI  - A mini dental implant-supported obturator application in a patient with partial
      maxillectomy due to tumor: case report.
AB  - Following a partial maxillectomy in a patient, the oral and nasal cavities remain
      open, providing a passageway for transmission of air and fluids between the 2
      cavities. In such cases the primary aim should be the construction of an implant
      supported obturator prosthesis with adequate retention, stability, and peripheral
      seal. In this case report, a 34-year-old female patient who underwent a class II
      (according to Okay et al.) partial maxillectomy 14 years before was fitted with
      an obturator that was supported by 5 mini dental implants. The reason for the
      preference of mini dental implants is the lack of adequate bone tissue for
      conventional implant placement in the resected area and the placement of mini
      dental implants with a simple surgical procedure. The treatment achieved
      restoration of the lost functions, which satisfied the patient, restoring her
      self-confidence and enhancing her quality of life. Thus, applying obturators
      supported by mini dental implants was successful and may be considered as an
      alternative to more complicated surgical techniques. Although the presented case
      is promising, further clinical research is needed to draw more definite
      conclusions.

PMID- 17197208
TI  - Successful treatment of oral linear IgA disease using mycophenolate.
AB  - Linear IgA disease (LAD) is a rare acquired autoimmune bullous disorder,
      characterized by linear deposition of IgA along the dermoepidermal basement
      membrane zone. The clinical presentation of LAD consists of vesiculobullous
      lesions affecting the skin and mucosal surfaces. The present case report presents
      a rare presentation of this vesiculobullous disorder. Although more than 50% of
      LAD patients present with oral lesions, there are few reported cases of
      involvement of the mouth as the sole manifestation. A 79-year-old female
      presented with a sore mouth and erosions affecting the palate. The symptoms
      resolved following the provision of mycophenolate, an antiproliferative
      immunosuppressant which has not previously appeared to have been reported in the
      long-term successful management of linear IgA disease limited to the mouth. We
      found that mycophenolate is a useful adjunct to the successful treatment of oral
      linear IgA when the uses of other immunosuppressants are contraindicated.

PMID- 17197209
TI  - Why the platelet-rich gel has antimicrobial activity?

PMID- 17197210
TI  - In vitro and in vivo performance of a novel surface treatment to enhance
      osseointegration of endosseous implants.
AB  - OBJECTIVE: This article shows the in vitro and in vivo characterization of a new
      biomimetic treatment developed to enhance the osseointegration of titanium dental
      implants. STUDY DESIGN: A novel biomimetic treatment of titanium was developed.
      Its physicochemical properties and biologic and in vivo performance were
      considered and studied. Mineralization capability was assessed by soaking test in
      simulated body fluid solution, and cytocompatibility was assessed using
      osteoblast-like MG63 cell culture. Histomorphometric analysis was performed at 3
      time points using a sheep animal model. RESULTS: In vitro tests confirmed the
      biomimetic potential of the considered novel treatment. Histomorphometric
      analysis indicated its potential for rapid and good-quality osseointegration.
      CONCLUSION: The in vitro and in vivo test results indicated that the proposed
      novel treatment possesses a significant potential to increase the rate of
      osteointegration of titanium for endosseous dental implants.

PMID- 17197212
TI  - Cyclin D1 expression in oral squamous cell carcinoma and verrucous carcinoma:
      correlation with histological differentiation.
AB  - OBJECTIVE: To assess the expression of cyclin D1 in oral squamous cell carcinoma
      (OSCC) and verrucous carcinoma (VC), to compare its expression in both of these
      carcinomas, and to investigate the possible correlation of cyclin D1 expression
      in different histological grades of OSCC. STUDY DESIGN: Paraffin embedded tissues
      from 71 cases of OSCC and VC were studied immunohistochemically. Expression of
      protein was correlated between the 2 entities and in different grades of OSCC.
      RESULTS: Cyclin D1 overexpression was seen in 29 cases (70.7%) of OSCC and in 19
      cases (63.3%) of verrucous carcinoma. Statistical significance at the 5% level
      was observed for cyclin D1 expression between all categories of squamous cell
      carcinoma (SCC), that is, between well-differentiated and moderately
      differentiated carcinomas, and between moderate and poorly differentiated
      carcinomas, and well and poorly differentiated squamous carcinomas. No
      statistical significance was observed in cyclin D1 expression between SCC and
      oral verrucous carcinoma; however, statistical significance was seen between oral
      VC and poorly differentiated squamous cell carcinoma. CONCLUSION: Increased
      expression of cyclin D1 significantly correlated with lack of differentiation in
      these malignant epithelial neoplasms.

PMID- 17197211
TI  - Remarkable response of juvenile diffuse sclerosing osteomyelitis of mandible to
      pamidronate.
AB  - We report a juvenile case of diffuse sclerosing osteomyelitis of the mandible
      that showed a favorable response to pamidronate, a bisphosphonate derivative.
      Although conventional treatments had been ineffective for 5 years, pamidronate
      administration brought about conspicuous improvement both clinically and
      radiographically. Severe adverse reaction was not found except for low-grade
      fever and lassitude on the day following administration. During the course of the
      treatment, however, nonsuppurative osteomyelitis of the right humerus also
      occurred, leading to the established diagnosis of chronic recurrent multifocal
      osteomyelitis. Pamidronate therapy was again performed successfully with near
      disappearance of clinical symptoms. Both bone-specific alkaline phosphatase (bone
      formation marker) and pyridinoline cross-linked carboxyterminal telopeptide of
      type I collagen (bone resorption marker) showed a marked decrease with
      pamidronate therapy, suggesting that pamidronate is useful for the treatment of
      chronic recurrent multifocal osteomyelitis with inhibitory effect on bone
      turnover.

PMID- 17197213
TI  - Periapical surgery and the maxillary sinus: radiographic parameters for clinical
      outcome.
AB  - OBJECTIVE: To find out whether conventional periapical radiographs can be used to
      determine the risk of creating an oroantral communication (OAC) while performing
      periapical surgery on maxillary premolars and molars. STUDY DESIGN: One hundred
      thirteen periapical radiographs of maxillary premolars and molars with periapical
      radiolucencies indicating chronic apical periodontitis were retrospectively
      analyzed and classified. The surgery reports were evaluated for occurrence of
      perforation of the maxillary sinus and postoperative complications. RESULTS:
      Perforation of the sinus membrane (also referred to as the Schneiderian membrane)
      occurred in 12 cases (9.6%). Exposure of the membrane without rupture occurred in
      15 cases (12%). It was found that the distance between the apex or the periapical
      lesion and the sinus floor did not serve as a predictor of a possible sinus
      membrane rupture. On the other hand, if the radiograph showed a distinct distance
      between the lesion and the sinus floor, there was an 82.5% probability that OAC
      would not occur. Additionally, a blurred radiographic outline of the periapical
      lesion did not indicate an increased risk of sinus membrane rupture. CONCLUSION:
      Conventional periapical radiographs cannot be used as predictors for perforation
      of the maxillary sinus during periapical surgery. However, radiographs with a
      specific distance between the periapical lesion and the sinus floor point toward
      a very low risk of accidental sinus perforation during periapical surgery.

PMID- 17197214
TI  - Managing chronic whiplash associated pain with a combination of low-dose opioid
      (remifentanil) and NMDA-antagonist (ketamine).
AB  - The aim was to investigate the efficacy of a combination of low-dose remifentanil
      (REMI) and ketamine (KET) compared to the single drugs and placebo (P) on
      whiplash associated pain (WAD) in a double-blind, randomized, placebo-controlled,
      cross-over study. Twenty patients with chronic (>1 year) WAD were included. Four
      different drug combinations were tested in four sessions: placebo/placebo (P/P),
      placebo/remifentanil (P/REMI), ketamine/placebo (KET/P) and ketamine/remifentanil
      (KET/REMI). Target concentrations were 1 and 2ng/ml (stepwise) for remifentanil
      and 100ng/ml for ketamine. Habitual pain intensity was assessed on a visual
      analogue scale (VAS). Experimental pain was assessed with electrical stimulation
      (single and repeated) of tibialis anterior (TA) muscle, pressure pain algometry
      applied over infraspinatus (IS) and TA muscles and VAS scores after intramuscular
      hypertonic saline infusion in TA. KET/REMI significantly reduced habitual pain.
      KET/REMI infused at low REMI target concentration (1ng/ml) significantly elevated
      electrical intramuscular pain thresholds (single and repeated). Pain thresholds
      to electrical stimulation were similarly increased by both P/REMI and KET/REMI at
      2ng/ml target concentration. Pressure pain thresholds were increased by both
      KET/REMI and P/REMI. VAS-scores after intramuscular saline were also similarly
      decreased by both REMI combinations. Seven out of 20 subjects were non-responders
      (<50% pain relief). No correlation was found between effects on spontaneous pain
      and experimental pain. KET/REMI showed an analgesic effect on habitual pain.
      Experimental pain was attenuated by both combinations containing the opioid,
      however, KET seemed to enhance the effect of REMI on electrical pain thresholds
      when a low REMI target concentration was used.

PMID- 17197215
TI  - Spatially uniform sampling in 4-D EPR spectral-spatial imaging.
AB  - Four-dimensional EPR imaging involves a computationally intensive inversion of
      the sampled Radon transform. Conventionally, N-dimensional reconstructions have
      been carried out with N-1 stages of 2-D backprojection to exploit a dimension
      dependent reduction in execution time. The huge data size of 4-D EPR imaging
      demands the use of a 3-stage reconstruction each consisting of 2-D
      backprojections. This gives three orders of magnitude reduction in computation
      relative to a single stage 4-D filtered backprojection. The multi-stage
      reconstruction, however, requires a uniform angular sampling that yields an
      inefficient distribution of gradient directions. We introduce a solution that
      involves acquisition of projections uniformly distributed in solid angle and
      reconstructs in three 2-D stages with the spatial uniform solid angle data set
      converted to uniform linear angular projections using 2-D interpolation. Images
      were taken from the two sampling schemes to compare the spatial resolution and
      the line width resolution. The degradation in the image quality due to the
      additional interpolation was small, and we achieved approximately 30% reduction
      in data acquisition time.

PMID- 17197216
TI  - Metabolic compensation and behavioral thermoregulation of subtropical rhacophorid
      (Polypedates megacephalus) tadpoles in container habitats.
AB  - We examined the relative importance of behavioral thermoregulation and metabolic
      compensation used by a subtropical rhacophorid (Polypedates megacephalus)
      tadpoles living in man-made container habitats to cope with thermal stress. We
      collected foam nests of P. megacephalus from man-made container habitats, and
      hatchlings were raised in 150 or 15 L of water (LWB and SWB containers,
      respectively). Water and air temperatures of containers were monitored using a
      datalogger. Tadpoles from both types of containers were acclimated at 22 and 32
      degrees C for 10 d before measuring oxygen consumption (V(O2)) in a closed-system
      at 22, 27, and 32 degrees C. Thermal selection of tadpoles from two containers
      was determined using an aquatic thermal gradient. We observed daily
      stratification of temperature in the water column of LWB containers but not SWB
      containers. Tadpoles from LWB and SWB containers exhibited metabolic compensation
      so that tadpoles acclimated to 22 degrees C had significantly higher V(O2) than
      those acclimated to 32 degrees C. This was probably related to the variation of
      environmental temperature experienced by the tadpoles. Tadpoles of LWB and SWB
      containers selected similar water temperatures with low coefficient of variation,
      suggesting they are good thermal selectors. Results of this study suggest that P.
      megacephalus tadpoles use both behavioral thermoregulation and metabolic
      compensation to cope with the environmental temperature fluctuation, and this is,
      in part, due to the heterogeneity in the thermal regimes of breeding habitats.
      Even though metabolic compensation of tadpoles incurs a cost, P. megacephalus
      tadpoles that experience no daily thermal gradient in the man-made water bodies
      and/or seasonal variations in temperature over tadpole period evolve metabolic
      compensation to maintain physiological homeostasis under different thermal
      regimes.

PMID- 17197217
TI  - Anti-cyclooxygenase effects of lipid extracts from the New Zealand green-lipped
      mussel, Perna canaliculus.
AB  - Total lipid extracts of P. canaliculus (a bivalve marine mollusc native to New
      Zealand, commonly called the green-lipped mussel) and Mytilus edulis (commonly
      called the common blue mussel) moderately inhibited ovine COX-1 and COX-2 pure
      enzymes in vitro. The inhibition was increased after the mussel extracts were
      saponified by KOH hydrolysis. Protease- and protease-lipase-hydrolysed lipid
      extracts of P. canaliculus exhibited similarly strong COX inhibition as the KOH
      hydrolysed extract. Lyprinol(R) (a commercial extract from P. canaliculus) also
      exhibited strong inhibition of both COX isoforms, an effect that was increased 10
      fold upon subsequent hydrolysis. In contrast, fish oil was not as anti-COX active
      as Lyprinol. The Lyprinol free fatty acid fraction, and to a lesser extent the
      Lyprinol triglyceride fraction, were the only lipid classes of Lyprinol to
      exhibit strong inhibition of the COX isoforms. The purified PUFA extracts were
      all bioactive, potently inhibiting COX-1 and COX-2. Incubation of Lyprinol in the
      absence of exogenous arachidonic acid (AA) showed the appearance of alternate
      prostaglandin metabolites, confirming Lyprinol PUFA as a competitive substrate
      inhibitor of AA metabolism.

PMID- 17197218
TI  - Determining Actinobacillus succinogenes metabolic pathways and fluxes by NMR and
      GC-MS analyses of 13C-labeled metabolic product isotopomers.
AB  - Actinobacillus succinogenes is a promising candidate for industrial succinate
      production. However, in addition to producing succinate, it also produces formate
      and acetate. To understand carbon flux distribution to succinate and alternative
      products we fed A. succinogenes [1-(13)C]glucose and analyzed the resulting
      isotopomers of excreted organic acids, proteinaceous amino acids, and glycogen
      monomers by gas chromatography-mass spectrometry and nuclear magnetic resonance
      spectroscopy. The isotopomer data, together with the glucose consumption and
      product formation rates and the A. succinogenes biomass composition, were
      supplied to a metabolic flux model. Oxidative pentose phosphate pathway flux
      supplied, at most, 20% of the estimated NADPH requirement for cell growth. The
      model indicated that NADPH was instead produced primarily by the conversion of
      NADH to NADPH by transhydrogenase and/or by NADP-dependent malic enzyme.
      Transhydrogenase activity was detected in A. succinogenes cell extracts, as were
      formate and pyruvate dehydrogenases, which the model suggested were contributing
      to NADH production. Malic enzyme activity was also detected in cell extracts,
      consistent with the flux analysis results. Labeling patterns in amino acids and
      organic acids showed that oxaloacetate and malate were being decarboxylated to
      pyruvate. These are the first in vivo experiments to show that the partitioning
      of flux between succinate and alternative fermentation products can occur at
      multiple nodes in A. succinogenes. The implications for designing effective
      metabolic engineering strategies to increase A. succinogenes succinate production
      are discussed.

PMID- 17197220
TI  - [Therapeutic strategies in superior sulcus tumors: a model for combined modality
      therapy in non-small cell lung cancer].
AB  - Superior sulcus tumors have been individualized among other non-small cell lung
      cancers because of their characteristic clinical presentation in connection with
      their local extension to the chest wall and the brachial plexus. For a long time
      considered as marginally resectable, superior sulcus tumors have been treated
      since the early 1960's, with a combined approach including preoperative
      radiotherapy and curative-intent surgery. Surgical resection includes both
      thoracic, cervical and neurosurgical approach, and aims at obtaining complete
      resection, which has been identified as a determining prognostic factor in most
      reported series. Two recent phase II trials showed the benefit, both regarding
      resectability and local control rates, and survival of combined therapeutic
      strategies including induction platinum-based chemoradiation, extensive surgical
      resection, and adjuvant chemotherapy. Adjuvant radiotherapy is not recommended at
      the time, but needs to be re-evaluated regarding its recent technical
      optimisation. Similarly to other locally advanced non-small cell lung cancers,
      exclusive chemoradiation is the standard treatment of unresectable superior
      sulcus tumors. In this way, radiotherapy has shown to offer a prolonged analgesia
      in more than 75% of cases, and is associated with concurrent or sequential
      chemotherapy, with comparable results to those observed in stage III lung cancer.
      These developments make superior sulcus tumors a therapeutic model for locally
      advanced non-small cell lung cancer, whereby the benefit of combined multimodal
      strategies including induction chemoradiation and surgical resection are
      currently evaluated in phase III trials.

PMID- 17197221
TI  - An unusual presentation of a rare chest wall tumour: giant cell tumour of bone.
AB  - Giant cell tumour of bone is an aggressive benign bone tumour. It rarely affects
      the ribs. It usually involves the posterior end of the ribs and literature
      regarding anterior end involvement is scanty. We report a case of giant cell
      tumour of the anterior end of the rib masquerading as a sub-mammary abscess in
      lactating women.

PMID- 17197219
TI  - Loss of apolipoprotein E exacerbates the neonatal lethality of the Smith-Lemli
      Opitz syndrome mouse.
AB  - The Smith-Lemli-Opitz syndrome (SLOS) is caused by a genetic defect in
      cholesterol biosynthesis; mutations in the enzyme 3ss-hydroxysterol Delta7
      reductase (Dhcr7) lead to a failure of cholesterol (and desmosterol) synthesis,
      with an accumulation of precursor sterols, such as 7-dehydrocholesterol.
      Extensive genotype-phenotype analyses have indicated that there is considerable
      variation in the severity of the disease, much of which is not explained by
      defects in the Dhcr7 gene alone. Factors ranging from variations in maternal
      fetal cholesterol transfer during pregnancy, to other genetic factors have been
      proposed to account for this variability. Variations at the APOE locus affect
      plasma cholesterol levels in humans and this polymorphic gene has been found to
      be associated with cardiovascular as well as neurological disorders. This locus
      has recently been implicated in accounting for some of the variations in SLOS. To
      address whether maternal hypercholesterolemia can affect fetal outcome, we tested
      the ability of maternal hypercholesterolemia to rescue the neonatal lethality in
      a mouse model of SLOS. Maternal hypercholesterolemia, induced by ApoE or Ldl-r
      deficiency not only failed to ameliorate the postnatal lethality, it increased
      the prenatal mortality of Dhcr7 deficient pups. Thus the murine data suggest that
      maternal loss of ApoE or Ldl-r function further exacerbates the neonatal
      lethality, suggesting they may play a role in maternal transfer of cholesterol to
      the embryo.

PMID- 17197222
TI  - Yersinia pseudotuberculosis infection of a lumbar facet joint.

PMID- 17197223
TI  - Calcaneous quantitative ultrasound measurements predicts vertebral fractures in
      idiopathic male osteoporosis.
AB  - OBJECTIVES: The aim of this study was to identify the differences in ultrasound
      bone variables (QUS) and to test the ability to discriminate male patients with
      and without vertebral fractures. METHODS: We therefore measured broadband
      ultrasound attenuation (BUA) and speed of sound (SOS) matched for bone mineral
      density (BMD) and vertebral deformity in idiopathic male osteoporosis. RESULTS:
      One hundred and seventeen men (age 56.6 range 27-78) were divided into three
      groups (osteoporosis n=25, osteopenia n=58 and age-matched control n=34)
      according to BMD T-score by WHO criteria. We found 66 patients (56%) with at
      least one vertebral deformity during the study. BMD and BUA did not differ, while
      SOS was lower in osteoporosis (p<0.001) and control group (p<0.001) between the
      patients with and without vertebral compression. Strong positive correlation was
      demonstrated between BUA and BMD (lumbar spine r=0.44, p<0.001, femoral neck
      r=0.56, p<0.001, radius r=0.40, p<0.001), while similar association between SOS
      and BMD values was not shown. There was no relationship between the BUA and
      vertebral fracture risk (Odds ratio: 1.14 95% CI: 0.80-1.61). However, the
      relative risk of vertebral fracture by SOS was 1.56 (95% CI: 1.08-2.62).
      Adjusting for age and BMI the risk of vertebral fracture did not change (odds
      ratio for SOS 1.50 95% CI: 1.02-2.22). After adjustment for BMD SOS was still
      associated with fracture risk at all measured sites (odds ratio: 1.43, 95% CI:
      1.02-2.22; 1.41, 95% CI: 1.02-2.17 and 1.32, 95% CI: 1.02-2.0). CONCLUSION: Our
      results suggest that BUA values are more closely related to density and structure
      while SOS values are able to predict fractures.

PMID- 17197224
TI  - Toluene inhalation induced neuronal damage in the spinal cord and changes of
      neurotrophic factors in rat.
AB  - We investigated the effects of toluene inhalation on neurons and neurotrophic
      factors in the spinal cord and the relationship between them. Male Wistar rats
      were exposed to toluene (1500ppm for 4h per day) for 7 days. To observe damage of
      the neurons in spinal cord with the toluene, expression of microtubule associated
      protein 2 (MAP2) and 70kDa heat shock protein (HSP70) in spinal cord were
      performed by immunohistochemistry. MAP2 was degraded and HSP70-immunoreactivity
      was enhanced in nerve cell bodies of the gray matter in toluene inhalation group.
      Immunoreactivity of glial fibrillary acidic protein (GFAP), a marker of
      astrocytes, was enhanced in the toluene-treated group. Furthermore, glial cell
      line-derived neurotrophic factor (GDNF)- and brain-derived neurotrophic factor
      (BDNF)-immunoreactivity in spinal cord were slightly decreased in the treated
      group. In addition, the concentrations of GDNF and BDNF in the spinal cord were
      determined using enzyme linked immunosorbent assay (ELISA). Concentration of GDNF
      was reduced significantly by toluene exposure. BDNF also reduced, but not
      significantly. The toluene inhalation caused the damage of the neuron in the
      spinal cord, which was accompanied by the decrease in the neurotrophic factors,
      such as BDNF and GDNF.

PMID- 17197225
TI  - Differences in postmortem urea nitrogen, creatinine and uric acid levels between
      blood and pericardial fluid in acute death.
AB  - Previous studies showed significant differences in postmortem urea nitrogen (UN),
      creatinine (Cr) and uric acid (UA) levels in heart blood depending on the causes
      of death, including acute death. In addition, the levels in pericardial fluid
      approximated the clinical serum reference ranges, and their elevations may be
      assessed based on clinical criteria. The present study investigated difference
      between blood and pericardial levels of these markers. Medicolegal autopsy cases
      (n=556, within 48h postmortem) of the following causes of death were examined:
      injury (n=136), asphyxiation (n=50), drowning (n=39), fire fatalities (n=99),
      hyperthermia (n=11), hypothermia (n=8), poisoning (n=26), delayed traumatic death
      (n=44) and natural diseases (n=143). When serum UN, Cr and UA levels were
      compared with the pericardial levels, there was an equivalency for delayed
      traumatic death and chronic renal failure, although each level was markedly
      elevated. Parallel increases in serum and pericardial UA and/or Cr levels were
      also observed for hypothermia and gastrointestinal bleeding. However, in drowning
      cases, the left cardiac and pericardial UN levels were lower than the right
      cardiac and peripheral levels, suggesting the influence of water aspiration.
      Significant elevations in serum and pericardial Cr and UA levels with a higher
      serum/pericardial UA ratio for fatal methamphetamine intoxication suggest
      progressive skeletal muscle damage due to advanced hypoxia/acidosis. Similar
      findings were often observed for other acute and subacute deaths. These findings
      suggest that a comparison between blood and pericardial nitrogenous compounds
      would be useful for investigating the cause and process of death.

PMID- 17197226
TI  - Genetic data for 16 Y-chromosomal STR loci in Japanese.
AB  - Allele frequencies and haplotypes for 16 Y-chromosome STR loci, DYS19, DYS389I,
      DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456,
      DYS458, DYS635, Y GATA H4, and DYS385a/b, were determined in 161 unrelated
      Japanese males using AmpFlSTR Yfiler PCR Amplification Kit. This population was
      demonstrated 153 haploytpes, of which 146 were unique, six were found in two
      individuals, and one was found in three individuals. The haplotypes diversity
      calculated from the 16 Y-STR loci was 0.9994 and the discrimination capacity was
      0.9503.

PMID- 17197227
TI  - Allele and haplotype distribution for 16 Y-STRs (AmpFlSTR Y-filer kit) in the
      state of Chihuahua at North Center of Mexico.
AB  - The AmpFlSTR Y-filer kit, including 16 Y-STRs was analyzed in 326 males from
      Chihuahua, at North Central, Mexico. Allele frequencies and gene diversity for
      each locus were estimated. Four allele duplications, namely DYS389II, DYS390,
      DYS391 and DYS439; and one allele null at DYS448 were observed in the sample. The
      haplotype diversity was 99.97+/-0.3%. The AMOVA results, including a previous
      report from West of Mexico (Jalisco), showed that most of the genetic variability
      between these Mexican populations is attributable to intrapopulational
      differences (99.87%). This result supports a low-genetic differentiation between
      males from North and West regions of Mexico.

PMID- 17197228
TI  - The correlation between unemployment and suicide rates in Japan between 1978 and
      2004.
AB  - The number of suicides in Japan has increased from approximately 22,000 per year
      from 1988 to 1997 to over 30,000 per year since then; this increase is among the
      most important problems facing Japan. Moreover, the unemployment rate in Japan
      has increased rapidly since 1998. In this study, we examined the total number of
      suicides and both the suicide and unemployment rates in Japan from 1978 to 2004.
      We also focused on the correlation between annual suicide rates in Japan and the
      annual unemployment rates during the study period. During that period, 455,357
      males and 225,012 females committed suicide in Japan, and the suicide rates by
      sex were 27.8 males and 13.3 females per 100,000 population (P<0.05). The annual
      suicide rates among males correlated significantly with the annual unemployment
      rates: r(27)=0.94, P<0.001, while the female suicide rates did not correlate with
      the unemployment rates: r(27)=0.39, P=0.05. Thus, when unemployed men are
      observed to be depressed, it is important for those close to them, as well as
      their health care professionals, to pay careful attention to their behavior to
      detect suicidal tendencies or intentions.

PMID- 17197229
TI  - Assessment of endoleak significance after endovascular repair of abdominal aortic
      aneurysms: a lumped parameter model.
AB  - The outcome of endovascular repair of abdominal aortic aneurysms (AAAs) is
      greatly compromised by the possible occurrence of endoleak. Previously, the
      causes and effects of endoleak on a patient-specific basis have mainly been
      investigated in experimental studies. In order to both reconcile and physically
      substantiate the various experimental findings, a lumped parameter model of an
      incompletely excluded AAA was developed. After experimental validation, the model
      was applied to study the effects on the intrasac pressure of the degree of
      endoleak, the degree of stent-graft compliance, and the resistance of a possible
      outflow tract formed by a branching vessel. It is concluded that the presence of
      endoleak leads to elevated intrasac pressure, the mean of which is mainly
      governed by the outflow tract resistance, while the pulse pressure is governed by
      both the endoleak resistance and the stent-graft compliance. Based on the
      agreement of the current results with previous findings, it is further concluded
      that the lumped parameter modelling method provides a useful numerical tool for
      validating experimental endoleak studies.

PMID- 17197230
TI  - Sensorimotor disturbances in chronic neck pain--range of motion, peak velocity,
      smoothness of movement, and repositioning acuity.
AB  - The purpose of this pilot study was to evaluate sensorimotor functions in
      patients with chronic neck pain with objective and quantitative methods. A group
      of 16 patients with chronic idiopathic neck pain of insidious onset or whiplash
      associated disorders (WAD) was compared to an equally sized group of healthy
      subjects. Kinematics were investigated during voluntary head rotations by
      measuring range of motion, variability of range of motion (ROM-Variability), peak
      velocity, and smoothness of movement (jerk index). Repositioning acuity after
      cervical rotations was evaluated by analysing constant and variable error (VE).
      In comparison to the healthy subjects, the patients showed significantly larger
      jerk index, ROM-Variability and VE. No statistically significant differences were
      found between insidious neck pain and WAD. It is concluded that jerky and
      irregular cervical movements and poor position sense acuity are characteristic
      sensorimotor symptoms in chronic neck pain. The observed individuality in
      sensorimotor disturbances emphasizes the importance of developing specific
      rehabilitation programs for specific dysfunctions, and of using objective and
      quantitative methods for evaluation of rehabilitation.

PMID- 17197231
TI  - The proteasome as a potential target for novel anticancer drugs and
      chemosensitizers.
AB  - A major challenge in cancer therapy is tumor drug resistance. To overcome it, it
      is essential to understand the mechanisms and identify the molecules involved, so
      that they can be specifically targeted in combination therapies. The proteasome
      is such a validated target: it plays a key role in cancer cell proliferation,
      inhibition of chemotherapy-induced apoptosis and drug resistance development.
      Bortezomib (Velcade, PS-341) was the first proteasome inhibitor to receive
      regulatory approval from the US Food and Drug Administration for the treatment of
      multiple myeloma. Clinical combination trials have demonstrated a chemo
      sensitizing effect of bortezomib on conventional agents in hematological
      malignancies and some solid tumors such as androgen-independent prostate and
      ovarian cancer. Although generally well-tolerated, bortezomib still generates
      toxicity which underscores the need for less toxic proteasome inhibitors. Several
      naturally occurring products, such as green tea polyphenols and the antibiotic
      lactacystin, have been shown to be potent proteasome inhibitors. Significantly,
      green tea polyphenols, as well as several flavonoids such as genistein, curcumin
      and resveratrol, have also been shown to have chemo-sensitizing properties in
      prostate, breast, hepatic, and lung tumors. Further studies on natural proteasome
      inhibitors as chemo-sensitizers could lead to identification of more potent and
      less toxic compounds that could be used in combination therapies for drug
      resistant tumors.

PMID- 17197232
TI  - Solvent effect on the luminescent properties of new europium and terbium nitrate
      complexes with 3,3,7,7-tetra[N-methyl-N-phenyl(acetamide)-2-oxymethyl]-5
      oxanonane.
AB  - The multipodal ligand 3,3,7,7-tetra[N-methyl-N-phenyl(acetamide)-2-oxymethyl]-5
      oxanonane (L) and its europium and terbium nitrate complexes were synthesized.
      The complexes were characterized by elemental analysis, IR, fluorescence
      spectroscopy and conductivity. The lanthanide atoms are coordinated by O atoms
      from CO, COC. With the difference of the solvent, the fluorescence properties of
      solvent effect for the complexes were investigated. Some factors that influencing
      the fluorescent intensity were discussed.

PMID- 17197233
TI  - Ab initio study of spectroscopic properties of CuAr, CuAr(+) and CuAr(-).
AB  - The spectroscopic properties of CuAr, CuAr(+) and CuAr(-) have been studied in
      detail using ab initio MP2, CCSD and CCSD(T) methods. The effect of basis set on
      spectroscopic properties of these molecular systems has also been investigated.
      Among these molecules, CuAr(+) is found to be more strongly bound than CuAr and
      CuAr(-). The spectroscopic properties of CuAr and CuAr(-) are calculated in
      Lennard-Jones potential and the spectroscopic properties of CuAr(+) are
      calculated in Morse potential. Most of the spectroscopic constants of CuAr,
      CuAr(+) and all the spectroscopic constants of CuAr(-) are first reported. Our
      calculated bond length, harmonic frequency and dissociation energy of CuAr and
      CuAr(+) agree very well with the existing theoretical results.

PMID- 17197234
TI  - Hydrolysis of minor glycerophospholipids of plasma lipoproteins by human group
      IIA, V and X secretory phospholipases A2.
AB  - We investigated the hydrolysis of the minor glycerophospholipids of human HDL(3),
      total HDL and LDL using human group IIA, V and X secretory phospholipases A(2)
      (sPLA(2)s). For this purpose we employed the enzyme and substrate concentrations
      and incubation times optimized for hydrolysis of phosphatidylcholine (PtdCho),
      the major glycerophospholipid of plasma lipoproteins. In contrast to PtdCho,
      which was readily hydrolyzed by group V and X sPLA(2)s, and to a lesser extent by
      group IIA sPLA(2), the minor ethanolamine, inositol and serine
      glycerophospholipids exhibited marked resistance to hydrolysis by all three
      sPLA(2)s. Thus, when PtdCho was hydrolyzed about 80%, the ethanolamine and
      inositol glycerophospholipids reached a maximum of 40% hydrolysis. The hydrolysis
      of phosphatidylserine (PtdSer), which was examined to a more limited extent,
      showed similar resistance to group IIA, V and X sPLA(2)s, although the group V
      sPLA(2) attacked it more readily than group X sPLA(2) (52% versus 39% hydrolysis,
      respectively). Surprisingly, the group IIA sPLA(2) hydrolysis remained minimal at
      10-15% for all minor glycerophospholipids, and was of the order seen for the
      PtdCho hydrolysis by group IIA sPLA(2) at the 4-h digestion time. All three
      enzymes attacked the oligo- and polyenoic species in proportion to their mole
      percentage in the lipoproteins, although there were exceptions. There was
      evidence of a more rapid destruction of the palmitoyl compared to the stearoyl
      arachidonoyl glycerophospholipids. Overall, the characteristics of hydrolysis of
      the molecular species of the lipoprotein-bound diradyl GroPEtn, GroPIns and
      GroPSer by group V and X sPLA(2)s differed significantly from those observed with
      lipoprotein-bound PtdCho. As a result, the acidic inositol and serine
      glycerophospholipids accumulated in the digestion residues of both LDL and HDL,
      and presumably increased the acidity of the residual particles. An accumulation
      of the ethanolamine glycerophospholipids in the sPLA(2) digestion residues also
      had not been previously reported. These results further emphasize the diversity
      in the enzymatic activity of the group IIA, V and X sPLA(2)s. Since these
      sPLA(2)s possess comparable tissue distribution, their combined activity may
      exacerbate their known proinflammatory and proatherosclerotic function.

PMID- 17197235
TI  - Ontogeny of mRNA expression and activity of long-chain acyl-CoA synthetase (ACSL)
      isoforms in Mus musculus heart.
AB  - Long-chain acyl-CoA synthetases (ACSL) activate fatty acids (FA) and provide
      substrates for virtually every metabolic pathway that catabolizes FA or
      synthesizes complex lipids. We have hypothesized that each of the five cloned
      ACSL isoforms partitions FA towards specific downstream pathways. Adult heart
      expresses all five cloned ACSL isoforms, but their independent functional roles
      have not been elucidated. Studies implicate ACSL1 in both oxidative and lipid
      synthetic pathways. To clarify the functional role of ACSL1 and the other ACSL
      isoforms (3-6), we examined ACS specific activity and Acsl mRNA expression in the
      developing mouse heart which increases FA oxidative pathways for energy
      production after birth. Compared to the embryonic heart, ACS specific activity
      was 14-fold higher on post-natal day 1 (P1). On P1, as compared to the fetus,
      only Acsl1 mRNA increased, whereas transcripts for the other Acsl isoforms
      remained the same, suggesting that ACSL1 is the major isoform responsible for
      activating long-chain FA for myocardial oxidation after birth. In contrast, the
      mRNA abundance of Acsl3 was highest on E16, and decreased dramatically by P7,
      suggesting that ACSL3 may play a critical role during the development of the
      fetal heart. Our data support the hypothesis that each ACSL has a specific role
      in the channeling of FA towards distinct metabolic fates.

PMID- 17197236
TI  - The many faces of ITAMs.
AB  - Innate and adaptive immune responses are regulated by receptors that signal
      through immunoreceptor tyrosine-based activation motifs (ITAMs). The molecular
      basis of ITAM signaling has been extensively characterized and serves as a model
      for receptor-mediated signal transduction. Src family kinases typically
      phosphorylate ITAMs on dual tyrosines, which enable recruitment and activation of
      Syk family kinases through binding to dual SH2 domains on these kinases. Examples
      of ITAM-based signaling that do not conform precisely to the standard model are
      becoming increasingly common. ITAMs that suppress signaling under specific
      conditions and activate under others have been described, as have ITAM-like
      signaling mechanisms using nonstandard sequence motifs. Elucidating the diversity
      of ITAM-based signaling mechanisms will clarify how activating signals generated
      by ITAMs are tightly regulated and will open opportunities for specific
      therapeutic manipulation of ITAM-based signaling pathways.

PMID- 17197238
TI  - The pathogenic role of tissue-resident immune cells in psoriasis.
AB  - Psoriasis is a common chronic inflammatory skin disease, the study of which might
      also be of considerable value to the understanding of other inflammatory and
      autoimmune-type diseases, such as rheumatoid arthritis, inflammatory bowel
      disease, multiple sclerosis and diabetes mellitus. There is clear evidence that T
      cells and dendritic cells have a central role in psoriasis. Based on recent data
      from humans and animal models, we propose that a psoriasis lesion can be
      triggered and sustained by the local network of skin-resident immune cells. This
      concept focuses attention on local, rather than systemic, components of the
      immune system for rationalized therapeutic approaches of psoriasis and possibly
      also other chronic inflammatory diseases.

PMID- 17197239
TI  - Opposing effects of Toll-like receptor stimulation induce autoimmunity or
      tolerance.
AB  - Toll-like receptor (TLR) activation by pathogens can induce the activation of
      diverse cell populations of the immune system and, therefore, can initiate or
      augment protective T-helper 1 immune responses. However, on a susceptible genetic
      background, TLR stimulation can also induce autoimmunity. The relative
      contribution of either microbe-derived or endogenous antigens, such as single
      stranded RNA and unmethylated DNA, to TLR stimulation and the development of
      specific autoimmune diseases are still debated. Here, we review the different
      possibilities. Furthermore, tolerance induction by TLRs, which originally had
      been postulated to be protective by limiting excessive inflammation and, thus,
      preventing septic shock, has come into focus as a mechanism to control
      autoimmunity by inhibiting dendritic-cell maturation. In some murine models of
      systemic lupus erythematosus, TLR9 deficiency results in a shift from anti
      nucleosome to TLR7-dependent anti-ribonucleoprotein IgG2a and IgG2b
      autoantibodies, and enhanced disease progression and mortality. Thus, not only
      can TLR signalling induce autoimmunity, but TLR(9) stimulation might also
      regulate tolerance.

PMID- 17197237
TI  - Statins and the vascular endothelial inflammatory response.
AB  - Statins reduce cholesterol synthesis and are widely used for the treatment of
      hyperlipidaemia and ischaemic heart disease. Besides their cholesterol-lowering
      effects, statins also possess broad immunomodulatory and anti-inflammatory
      properties. Vascular endothelial cells have a crucial role in the pathogenesis of
      inflammatory disease, and, alongside leukocytes and antigen-presenting cells,
      represent a key cellular target for statin therapy. Recent studies investigating
      how these drugs modify endothelial cell function demonstrate that the therapeutic
      effect of statins can be attributed, in part, to their action on the endothelium.
      Accordingly, statins attenuate endothelial MHC class II expression, increase
      endothelial nitric oxide synthase and fibrinolytic activity, decrease leukocyte
      adhesion and transmigration, and enhance resistance to local injurious stimuli.
      Many of these effects are brought about by the modulation of small GTPase
      function and the downregulation of proinflammatory gene expression.

PMID- 17197240
TI  - Outside looking in: the inner workings of the cross-presentation pathway within
      dendritic cells.
AB  - The entry of exogenous antigen into the MHC class I-restricted cross-presentation
      pathway can contribute to CD8(+) T cell tolerance and immunity, in particular to
      peripheral self-antigens or selected viruses and bacteria showing restricted
      tissue tropism. Dendritic cells are the key cross-presenting cells and, as such,
      they are thought to carry specialized machinery dedicated to this purpose. Two
      recent papers describe intracellular components tailored to the dendritic cell
      cross-presentation pathway.

PMID- 17197241
TI  - Niche-to-niche migration of bone-marrow-derived cells.
AB  - During ontogenesis, haematopoietic stem cells (HSCs) relocate between extra
      embryonic and embryonic compartments. Similarly, site-specific homing of HSCs is
      ongoing during adulthood. With the expanding knowledge of HSC physiology, a new
      paradigm emerges in which HSCs and haematopoietic progenitor cells (HPCs) migrate
      to defined microenvironments within the bone marrow (BM) and to 'activated' or
      'inducible' niches elsewhere. Here, we summarize current understanding of HSC
      niche characteristics, and the physiological and pathological mechanisms that
      guide HSC homing both within the BM and to distant niches in the periphery,
      promoting new vessel growth in tumours and ischaemia. Recent observations suggest
      that features of the HSC niche might also be recapitulated in pre-metastatic
      sites. Clusters of BM-derived HPCs promote invasion of disseminating cancer
      cells. Clear clinical benefits can be foreseen by modulating HSCs and their
      microenvironments, in promoting tissue regeneration, and inhibiting
      tumourigenesis and cancer metastasis.

PMID- 17197242
TI  - Self-reported physical activities in patients after the Mustard or Senning
      operation: comparison with healthy control subjects.
AB  - BACKGROUND: Some decades ago, the Mustard or Senning operation was used to treat
      patients who were born with Transposition of the Great Arteries (TGA). Although
      life expectancy is good, previous studies have demonstrated limitations in
      exercise capacity. To what extent these limitations affect day-to-day functioning
      of the patients is not yet known. AIMS: We therefore investigated self-reported
      physical activities in patients after the Mustard or Senning operation, compared
      this with those of matched, healthy counterparts, and explored potential
      associations with age, gender and complexity of the TGA. METHODS: Seventy
      patients were matched with healthy controls. Habitual physical activity was
      measured using the Baecke questionnaire, resulting in a work, sports, and leisure
      time index, which ranges from 1 to 5. RESULTS: The median index scores of
      patients were 2.63 for work, 2.50 for sports; and 2.75 for leisure time. Only for
      sports, a significantly lower index score was found in patients. Furthermore, we
      found that older patients were less frequently engaged in sport activities
      (Spearman's rho=-0.38; p=0.02). CONCLUSION: The results showed that the level of
      physical activities of patients after the Mustard and Senning operation is
      normal, except for sport activities. This indicates that patients after a Mustard
      or Senning operation tend to partake in all activities that they can comfortably
      perform.

PMID- 17197243
TI  - A multi-perforated man: asymptomatic ruptured sinus of Valsalva aneurysm
      associated with an atrial and ventricular septal defect.
AB  - We report the case of an exceptional association of a right coronary sinus of
      Valsalva aneurysm (SVA) ruptured into the right ventricle, a supracristal
      ventricular septal defect (VSD) and an atrial septal defect (ASD). Our patient
      was totally asymptomatic and the diagnosis was established by echocardiography.
      The patient underwent prompt surgery that consisted in closing the aneurysm and
      the VSD with a pericardium patch.

PMID- 17197244
TI  - Flail mitral and tricuspid valves due to myxomatous disease.
AB  - Myxomatous disease generally affects mitral valve. However, tricuspid valves also
      can be involved in 20% of the myxomatous mitral valve disease. Valve prolapse,
      elongation of chordae and chordae rupture are generally seen complications of the
      myxomatous disease. There are some reports about severe tricuspid regurgitation
      due to tricuspid valve prolapse and elongated chordae, but no tricuspid and
      mitral chordae ruptures in the same patient due to myxomatous disease have been
      reported. In this case tricuspid chordae rupture accompanied to mitral chordae
      rupture is discussed.

PMID- 17197245
TI  - The complex relationship between seizures and behavior: an illustrative case
      report.
AB  - Epilepsy and behavior have a complex, often intriguing relationship. We report
      here the interesting case of Mrs. A, who presented with depression and developed
      seizures and an ictal psychosis precipitated by use of a selective serotonin
      reuptake inhibitor. She subsequently presented with forced normalization
      characterized by affective somatoform and hysterical manifestations.

PMID- 17197246
TI  - A statistical methodology for analyzing co-occurrence data from a large sample.
AB  - Determining important associations among items in a large database is challenging
      due to multiple simultaneous hypotheses and the ability to select weak
      associations that are statistically but not clinically significant. The simple
      application of the chi2 test among all possible pairs of items results in mostly
      inappropriate associations surpassing the traditional (alpha=.05, chi2=3.94)
      threshold. One can choose a stricter threshold to find stronger associations, but
      the choice may be arbitrary. We combined the volume test of Diaconis and Efron
      with a p-value plot to select a more rigorous and less arbitrary threshold. The
      volume test adjusts the p-value of the chi2-statistic. A plot of adjusted p
      values (1 - p versus N(p)), where N(p) is the number of test statistics with a p
      value greater than p, should be linear if there are no true associations. The
      point where the plot deviates from a line can be used as a threshold. We used
      linear regression to select the threshold in a reproducible fashion. In one
      experiment, we found that the method selected a threshold similar to that
      previously obtained by manually reviewing associations.

PMID- 17197248
TI  - Vascular endothelium summary statement I: Health promotion and chronic disease
      prevention.
AB  - The endothelium can be considered a discrete organ with pathophysiologic
      implications and as such has both diagnostic and therapeutic possibilities. It is
      essential for the normal function of the cardiovascular, cerebrovascular,
      renovascular, and pulmonary vascular system. The endothelium is directly involved
      in the development and progression of heart disease, stroke, peripheral vascular
      disease, venous thrombosis, insulin resistance, diabetes, chronic kidney failure,
      tumor growth, metastases and adverse reproductive outcomes for both the mother
      and her newborn child. Consequently the endothelium represents an objective
      biological determinant on which to base new multidisciplinary prevention and
      health promotion strategies. This summary statement suggests some possible
      avenues for clinical and public health research.

PMID- 17197247
TI  - A fuzzy system for helping medical diagnosis of malformations of cortical
      development.
AB  - Malformations of the cerebral cortex are recognized as a common cause of
      developmental delay, neurological deficits, mental retardation and epilepsy.
      Currently, the diagnosis of cerebral cortical malformations is based on a
      subjective interpretation of neuroimaging characteristics of the cerebral gray
      matter and underlying white matter. There is no automated system for aiding the
      observer in making the diagnosis of a cortical malformation. In this paper a
      fuzzy rule-based system is proposed as a solution for this problem. The system
      collects the available expert knowledge about cortical malformations and assists
      the medical observer in arriving at a correct diagnosis. Moreover, the system
      allows the study of the influence of the various factors that take part in the
      decision. The evaluation of the system has been carried out by comparing the
      automated diagnostic algorithm with known case examples of various malformations
      due to abnormal cortical organization. An exhaustive evaluation of the system by
      comparison with published cases and a ROC analysis is presented in the paper.

PMID- 17197249
TI  - Vascular endothelium summary statement V: Pulmonary hypertension and acute lung
      injury: public health implications.
AB  - Although relatively rare, pulmonary hypertension can be devastating for those
      individuals who are affected and has significant societal implications. The 2003
      WHO classification separates PAH (idiopathic, specific disease linked) from
      pulmonary hypertension related to lung disease, thromboembolic disease, and
      pulmonary venous hypertension. Another form of pulmonary hypertension, persistent
      pulmonary hypertension (PPHN), occurs in the newborn. In general, PPHN is thought
      to be responsible for approximately 10% of admissions to neonatal intensive care
      units and can be a complicating factor in 5 of 1000 live births. Acute lung
      injury (ALI) and the acute respiratory distress syndrome (ARDS) are complex
      disorders that pose a significant threat to critically ill patients. They are
      usually related to direct lung injury or indirect injury from sepsis, trauma, and
      other disorders. Although these pulmonary disorders reflect distinct
      pathophysiologic mechanisms, current evidence strongly suggests that a common
      denominator underlying many of the established molecular and cellular elements is
      endothelial cell activation and dysfunction. This summary statement briefly
      summarizes the state of the science and suggests future avenues of public health
      research.

PMID- 17197250
TI  - Comparison of the antiatherosclerotic effects of dihydropyridine calcium channel
      blocker and HMG-CoA reductase inhibitor on hypercholesterolemic rabbits.
AB  - The antiatherosclerotic effects of the dihydropyridine-type calcium channel
      blocker, benidipine hydrochloride (benidipine), and 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor, pravastatin sodium (pravastatin), were compared
      in hypercholesterolemic rabbits. Male, New Zealand white rabbits were fed a 0.5%
      cholesterol diet. Pravastatin (10 mg/kg) or benidipine (10 mg/kg) was orally
      administered once daily after start of feeding. After 8 weeks of cholesterol
      feeding, serum cholesterol was increased and endothelial function of thoracic
      aorta was impaired. Pravastatin prevented elevation of serum cholesterol and
      aortic tunica intima hyperplasia. Although benidipine had little effect on serum
      cholesterol, it significantly inhibited aortic tunica intima hyperplasia and
      impairment of endothelial function. Expression levels of the vascular cell
      adhesion molecule-1 (VCAM-1) and lectin-like oxidized low-density lipoprotein
      receptor-1 (LOX-1) mRNA in aorta of hypercholesterolemic rabbit were higher than
      those of normal rabbit. Benidipine significantly prevented upregulation of VCAM-1
      mRNA expression and showed a tendency to inhibit elevation of LOX-1 mRNA
      expression. Pravastatin significantly prevented upregulation of both VCAM-1 and
      LOX-1 mRNA expression. The results demonstrate that pravastatin inhibits increase
      of serum cholesterol and vascular dysfunction in hypercholesterolemic rabbit.
      Benidipine is effective in preventing vascular hyperplasia without altering serum
      cholesterol levels and this may be due to inhibition of expression of VCAM-1.

PMID- 17197251
TI  - The impact of Cardiovascular Autonomic Neuropathy in diabetes: is it associated
      with left ventricular dysfunction?
AB  - Cardiovascular Autonomic Neuropathy (CAN) is one of the least understood of all
      serious complications of diabetes. Besides increasing mortality, CAN may have
      various clinical sequelae including exercise intolerance, arrhythmias and
      painless myocardial infarction. But does it also cause left ventricular
      dysfunction? Patients with diabetes have a greater risk of developing congestive
      heart failure. Coronary artery disease and hypertension have been notorious in
      causing left ventricular dysfunction in many of these patients. However, even in
      their absence, diabetes itself, through several studies, has been proposed to
      cause the controversial entity, Diabetic Cardiomyopathy (DCM). Various mechanisms
      have been suggested. CAN through alteration in myocardial blood flow and
      sympathetic denervation, and through changes in myocardial neurotransmitters,
      including catecholamines and neurotransmitters of the neuropeptidergic system,
      has been and is still being studied as one of the main mechanisms to cause left
      ventricular dysfunction. Earlier detection of CAN and instant initiation of
      upcoming treatments may be a way to help prevent DCM, and thus improve the
      morbidity and mortality this causes to patients with diabetes.

PMID- 17197252
TI  - Is the repair of oxidative DNA base modifications inducible by a preceding DNA
      damage induction?
AB  - In mammalian cells, 7,8-dihydro-8-oxoguanine (8-oxoG) and some other oxidative
      guanine modifications are removed from the DNA by base excision repair, which is
      initiated by OGG1 protein. We have tested whether this repair is inducible in
      mouse embryonic fibroblasts (MEFs), MCF-7 breast cancer cells and primary human
      fibroblasts by a pretreatment with the photosensitizer Ro19-8022 plus light,
      which generates predominantly 8-oxoG, or with methyl methanesulfonate (MMS),
      which generates alkylated bases and abasic sites (AP sites). The results indicate
      that the repair rate of the oxidative guanine modifications induced by the
      photosensitizer was not increased if a priming dose of the oxidative or
      alkylating agent was applied 6 or 18h prior to a challenging dose, although
      pretreatments with both agents resulted in two-fold elevated glutathione levels
      as an indication for an adaptive response. Similarly, the activity of total
      protein extracts of the cells to incise at a single 8-oxoG residue in an
      oligonucleotide was unchanged. It has to be concluded that the repair of 8-oxoG
      is not inducible by oxidative or alkylation damage.

PMID- 17197254
TI  - Simultaneous measurement of intracellular triphosphate metabolites of zidovudine,
      lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by
      combined anion exchange solid phase extraction and LC-MS/MS.
AB  - All nucleoside reverse transcriptase inhibitors (NRTI) must first be metabolized
      to their triphosphate forms in order to be active against HIV. Zidovudine (ZDV),
      abacavir (ABC) and lamivudine (3TC) have proven to be an efficacious combination.
      In order simultaneously to measure intracellular levels of the triphosphates (
      TP) of ZDV, ABC (carbovir, CBV) and 3TC, either together or individually, we have
      developed a cartridge-LC-MS/MS method. The quantitation range was 2.5-250
      pg/microl for 3TC-TP, 0.1-10.0 pg/microl for ZDV-TP and 0.05-5.00 pg/microl for
      CBV-TP. This corresponds to 0.1-11.0 pmol 3TC-TP per million cells, 4-375 fmol
      ZDV-TP per million cells and 2-200 fmol CBV-TP per million cells, extracted from
      10 million cells. Patient samples demonstrated measured levels in the middle
      regions of our standard curves both at pre-dose and 4h post-dose times.

PMID- 17197253
TI  - Asymmetric dimethylarginine--comparison of HPLC and ELISA methods.

PMID- 17197255
TI  - Bacterial elongation factors EF-Tu, their mutants, chimeric forms, and domains:
      isolation and purification.
AB  - Prokaryotic elongation factors EF-Tu form a family of homologous, three-domain
      molecular switches catalyzing the binding of aminoacyl-tRNAs to ribosomes during
      the process of mRNA translation. They are GTP-binding proteins, or GTPases.
      Binding of GTP or GDP regulates their conformation and thus their activity.
      Because of their particular structure and regulation, various activities (also
      outside of the translation system) and a relative abundance they represent
      attractive tools for studies of many basic but still not fully understood
      mechanisms both of the translation process, the structure-function relationships
      in EF-Tu molecules themselves and proteins and energy transduction mechanisms in
      general. The review critically summarizes procedures for the isolation and
      purification of native and engineered eubacterial elongation factors EF-Tu and
      their mutants on a large as well as small scale. Current protocols for the
      purification of both native and polyHis-tagged or glutathione-S-transferase (GST)
      tagged EF-Tu proteins and their variants using conventional procedures and the Ni
      NTA-Agarose or Glutathione Sepharose are presented.

PMID- 17197256
TI  - A novel high sensitivity HPLC assay for topiramate, using 4-chloro-7
      nitrobenzofurazan as pre-column fluorescence derivatizing agent.
AB  - A new, sensitive and simple high-performance liquid chromatographic method for
      analysis of topiramate, an antiepileptic agent, using 4-chloro-7
      nitrobenzofurazan as pre-column derivatization agent is described. Following
      liquid-liquid extraction of topiramate and an internal standard (amlodipine) from
      human serum, derivatization of the drugs was performed by the labeling agent in
      the presence of dichloromethane, methanol, acetonitrile and borate buffer (0.05
      M; pH 10.6). A mixture of sodium phosphate buffer (0.05 M; pH 2.4): methanol
      (35:65 v/v) was eluted as mobile phase and chromatographic separation was
      achieved using a Shimpack CLC-C18 (150 x 4.6 mm) column. In this method the limit
      of quantification of 0.01 microg/mL was obtained and the procedure was validated
      over the concentration range of 0.01 to 12.8 microg/mL. No interferences were
      found from commonly co-administrated antiepileptic drugs including phenytoin,
      phenobarbital carbamazepine, lamotrigine, zonisamide, primidone, gabapentin,
      vigabatrin, and ethosuximide. The analysis performance was carried-out in terms
      of specificity, sensitivity, linearity, precision, accuracy and stability and the
      method was shown to be accurate, with intra-day and inter-day accuracy from -3.4
      to 10% and precise, with intra-day and inter-day precision from 1.1 to 18%.

PMID- 17197259
TI  - Organ donation: the gift of life.

PMID- 17197260
TI  - Make genetics part of your world.

PMID- 17197261
TI  - School support for alternative lunches.

PMID- 17197262
TI  - Hey everyone, dinner's ready...two weeks ago!

PMID- 17197263
TI  - How does a lobbyist add value to dietetics advocacy?

PMID- 17197264
TI  - Need for and effectiveness of menu labeling.

PMID- 17197266
TI  - Dairy products and bone health.

PMID- 17197268
TI  - Postpartum weight control: a vicious cycle.

PMID- 17197269
TI  - Predictors of obesity among children living in Mexico City.

PMID- 17197270
TI  - Dietary adherence and associated glycemic control in families of young children
      with type 1 diabetes.
AB  - OBJECTIVE: This study examined the dietary intake, dietary adherence, and
      associated daily glycemic control of young children (mean age 5.6+/-1.6 years)
      with type 1 diabetes in 33 families. DESIGN: This was a one-sample cross
      sectional study. Children's nutrient and energy intakes were measured using 3-day
      diet diaries. Children's mean daily blood glucose levels were assessed
      prospectively for 2 weeks using the FreeStyle (TheraSense, Inc, Alameda, CA) home
      blood glucose meter. STATISTICAL ANALYSIS: Means, standard deviations, and
      frequencies described the sample. Associations between dietary adherence and
      glycemic control were examined by one-tailed Pearson correlations. RESULTS: Mean
      nutrient intakes were less than the Dietary Reference Intake for children's
      intake of vitamin B-12 and calcium. Children's dietary deviations revealed better
      than-predicted adherence to the number and timing of feedings per day and number
      of carbohydrate units consumed per meal. In contrast, children's daily
      carbohydrate intake was approximately 80%+/-21% of the recommended levels based
      on their weight and age. In addition, children's energy intake was only 78%+/-18%
      of the recommended levels based on age. Correlations revealed a positive
      association between poor dietary adherence and higher blood glucose levels.
      CONCLUSIONS: Young children with type 1 diabetes are likely to have adequate
      dietary intake of most micronutrients. However, their adherence to specific
      carbohydrate and energy intake recommendations may be lower. Because the
      preschool years represent a period of rapid growth, diet plans for preschoolers
      with diabetes need to be revised often for optimal management of type 1 diabetes.
      Close adherence to dietary recommendations is one behavior that may improve blood
      glucose control in young children with diabetes.

PMID- 17197271
TI  - Television watching and frequency of family meals are predictive of overweight
      onset and persistence in a national sample of school-aged children.
AB  - OBJECTIVE: To identify eating and activity factors associated with school-aged
      children's onset of overweight and persistent overweight. DESIGN: Data were
      gathered at four time points between kindergarten entry and spring of third
      grade. Children were directly weighed and measured and categorized as not
      overweight (<95th percentile of body mass index) or overweight (> or =95th
      percentile body mass index); parents were interviewed by telephone or in person.
      SUBJECTS/SETTING: Subjects were participants in the Early Childhood Longitudinal
      Study-Kindergarten Cohort, a nationally representative sample of children who
      entered kindergarten during 1998-1999. Children who weighed <2,000 g at birth,
      received therapeutic services before kindergarten, skipped or repeated a grade,
      or without complete height and weight data were excluded, resulting in 8,459
      participants. Children with intermittent overweight were not examined (n=459);
      analyses addressed 8,000 children. MAIN OUTCOME MEASURES: Three mutually
      exclusive groups of children were identified: never overweight, overweight onset,
      and persistent overweight. STATISTICAL ANALYSES PERFORMED: Multilevel,
      multivariate logistic regression analyses estimated the effects of eating and
      activity factors on the odds of overweight onset and persistent overweight above
      child sex, race, and family socioeconomic status. RESULTS: Children who watched
      more television (odds ratio [OR] 1.02) and ate fewer family meals (OR 1.08) were
      more likely to be overweight for the first time at spring semester of third
      grade. Children who watched more television (OR 1.03), ate fewer family meals (OR
      1.08), and lived in neighborhoods perceived by parents as less safe for outdoor
      play (OR 1.32) were more likely to be persistently overweight. Child aerobic
      exercise and opportunities for activity were not associated with a greater
      likelihood of weight problems. CONCLUSIONS: This study supports theories
      regarding the contributions of television watching, family meals, and
      neighborhood safety to childhood weight status. When working with families to
      prevent and treat childhood weight problems, food and nutrition professionals
      should attend to children's time spent with screen media, the frequency of family
      mealtimes, and parents' perceptions of neighborhood safety for children's outdoor
      play.

PMID- 17197272
TI  - Promoting family meals and placing limits on television viewing: practical advice
      for parents.

PMID- 17197273
TI  - Assessing the effect of underreporting energy intake on dietary patterns and
      weight status.
AB  - OBJECTIVES: To identify misreporting among older rural adults using a prediction
      algorithm and to compare dietary patterns of underreporters and plausible
      reporters. DESIGN: In this cross-sectional study, diet information was assessed
      by five 24-hour recalls collected over 10 months. All foods were classified into
      24 food subgroups. Demographic, health, and anthropometric data were collected
      via home visit. SETTING: Rural Pennsylvania. SUBJECTS: One hundred seventy-nine
      community-dwelling adults, aged 66 to 87 years. STATISTICAL ANALYSIS: Cluster
      analysis. RESULTS: Underreporters (n=43) were more likely than plausible
      reporters (n=133) to be overweight and less educated but did not differ by sex.
      Underreporters consumed fewer servings across the majority of food groups. Two
      dietary patterns were determined for all and plausible reporters, in both cases
      one of higher and one of lower nutrient density. Using only plausible reporters
      to determine dietary patterns was very similar to using all reporters. The
      correlation between energy intake and weight status was improved for plausible
      reporting women, but not men. CONCLUSIONS: Dietary patterns of plausible
      reporters were generally similar to that of all reporters; however, correlations
      with energy intake and weight status improved for women using only plausible
      reporters. Individuals may not accurately report dietary intake. Those obtaining
      diet reports should be aware of reporting errors before making decisions about
      dietary adequacy.

PMID- 17197274
TI  - Personal and professional correlates of US medical students' vegetarianism.
AB  - OBJECTIVE: To determine prevalence and correlates of US medical students' self
      identification as vegetarians. DESIGN: Medical students were anonymously surveyed
      via questionnaire three times: at freshmen orientation, orientation to wards, and
      during senior year. SUBJECTS: Medical students in the Class of 2003 (n=1,849) at
      15 US medical schools (response rate 80%). OUTCOME MEASURES: We examined self
      reported vegetarianism, abstinence from meat items on a food frequency
      questionnaire, and associations between students' vegetarianism and their health
      related outcomes. STATISTICAL ANALYSES: Bivariate associations were tested with
      chi(2) tests. RESULTS: During medical school, 7.2% of students self-identified as
      vegetarians; this percentage declined over time. Those who were vegetarians for
      health reasons (66% of vegetarians) ate more fruits and vegetables than those who
      were vegetarians for nonhealth reasons (P=0.02). Vegetarians were more likely
      (P<0.01) than nonvegetarians to eat more fruits and vegetables (P=0.002); be
      women (P=0.009); be Hindu, Buddhist, or Seventh Day Adventist (P< or =0.0004); be
      politically liberal (P=0.007); have a body mass index < or =25 (P=0.008); or, as
      freshmen, to perceive nutrition counseling as highly relevant to their intended
      practices (P=0.007). Vegetarian students were no more likely to counsel patients
      about nutrition than were nonvegetarians. CONCLUSIONS: Prevalence of
      vegetarianism was higher among US medical students than among other US adults,
      although the prevalence declined during medical school. Medical students and
      physicians with healthful personal practices are more likely to encourage such
      behaviors in their patients, although the specific nutrition habit of
      vegetarianism among medical students was unassociated with their nutrition
      counseling practices.

PMID- 17197275
TI  - Obesity increases metabolic syndrome risk factors in school-aged children from an
      urban school in Mexico city.
AB  - OBJECTIVE: To characterize the nutritional status of school-aged children from an
      urban public school in Mexico City, Mexico, and to assess the influence of
      obesity on health status in a subgroup of these children. DESIGN: Cross-sectional
      descriptive study. A nutrition screening was done for all children, including
      anthropometric (ie, weight, height, and waist circumference) and blood pressure
      assessment. In the subgroup of children, complementary dietary and biochemical
      assessment (ie, glucose, total cholesterol, high-density lipoprotein cholesterol,
      low-density lipoprotein cholesterol, triglyceride, insulin, albumin, hemoglobin,
      and hematocrit levels) was done. SUBJECTS: Children from an urban school in
      Mexico City (N=561) aged 6 to 13 years. The representative subgroup (n=88) was
      selected based on age (9 to 12 years) and weight status (ie, normal, overweight,
      or obese). STATISTICAL ANALYSIS: Descriptive statistics, correlations, mean
      differences tests (analysis of variance, Kruskal-Wallis and Mann-Whitney U), and
      chi(2) tests (categorical variables) were done with SPSS version 13 (2005, SPSS
      Inc, Chicago, IL). RESULTS: In the whole school, overweight and obesity
      prevalence were 27.1% and 21.4%, respectively. High systolic blood pressure was
      seen in 8.4% of children and 6.2% of children had prehypertension. Higher
      hypertension risk was seen in children with body mass index > or =95th percentile
      and waist circumference > or =90th percentile (88 cm). Significantly higher waist
      circumference, systolic blood pressure, insulin resistance indexes, and
      triglyceride levels were found among the obese when compared with normal-weight
      children. CONCLUSIONS: Childhood obesity prevalence is high in Mexico and it is
      having an influence on children's health. It is urgent to design, implement, and
      evaluate specific childhood obesity prevention programs.

PMID- 17197276
TI  - Behavior therapy and cognitive-behavioral therapy of obesity: is there a
      difference?
AB  - Current practice guidelines for management of overweight and obesity recommend a
      program of diet, exercise, and behavior therapy for all persons with a body mass
      index (calculated as kg/m(2)) of at least 30 (and those with body mass index > or
      =25 plus two weight-related comorbidities). In this tripartite treatment--often
      referred to as lifestyle modification--behavior therapy provides a structure that
      facilitates meeting goals for energy intake and expenditure. Although standard
      behavior therapy reliably induces mean weight losses of approximately 10% of
      initial weight, these reductions are difficult to maintain. Some authors argue
      that a shift in focus from behavior change to cognitive change will improve long
      term results of lifestyle modification programs. This review describes, in
      detail, the standard behavioral treatment of obesity and compares it with an
      alternative treatment model that is based in a cognitive conceptualization of
      weight control. A review of the literature suggests that the differences between
      standard behavior therapy and cognitive-behavioral therapy of obesity lie more in
      their underlying theories than in their implementation. Empirical comparisons of
      the long-term effects of these approaches are needed.

PMID- 17197277
TI  - Inpatient management of diabetes and hyperglycemia: implications for nutrition
      practice and the food and nutrition professional.
AB  - Although numerous guidelines and standards address the management of diabetes in
      outpatient settings, only recently has evidence been provided to issue standards
      of care to guide clinicians in optimal inpatient glycemic control for
      hospitalized individuals with diabetes or illness-induced hyperglycemia. Both the
      American Diabetes Association and the American College of Endocrinology recommend
      critically ill patients keep their blood glucose level as close to 110 mg/dL (6.1
      mmol/L) as possible. In the noncritically ill patient, the American Diabetes
      Association recommends to keep pre-meal blood glucose as close to 90 to 130 mg/dL
      (5.0 to 7.2 mmol/L) as possible, whereas the American College of Endocrinology
      recommends pre-meal blood glucose be kept at 110 mg/dL (6.1 mmol/L) or less. Both
      organizations agree that peak post-prandial blood glucose should be 180 mg/dL
      (10.0 mmol/L) or less. Recent evidence has also led the Joint Commission on
      Accreditation of Healthcare Organizations to develop standards for a voluntary
      certification in the management of the patient with diabetes in the inpatient
      setting. It is important that food and nutrition professionals familiarize
      themselves with these recommendations and implement nutrition interventions in
      collaboration with other members of the health care team to achieve these new
      glycemic control targets. Food and nutrition professionals have a key role in
      developing screening tools, and in implementing nutrition care guidelines,
      nutrition interventions, and medical treatment protocols needed to improve
      inpatient glycemic control.

PMID- 17197278
TI  - Validation of dietary intake data in black women with type 2 diabetes.
AB  - The validity of baseline dietary intake data in women participating in a
      culturally competent intervention study for black women with type 2 diabetes was
      assessed. The relationship of sociodemographic and physiologic factors with
      underreporting of dietary intake was determined. Criterion validity of dietary
      intake, which had been assessed using the Nutritionist Five Collection Form, a
      combination of a standard 2-day dietary recall and a modified, culturally
      appropriate food frequency questionnaire, was determined. Data were analyzed
      using First Data Bank Nutritionist Five (version 2.3, 2000, First Data Bank, San
      Bruno, CA) software. Validation of baseline dietary data in 109 women was
      performed by calculating the ratio of energy intake to resting metabolic rate.
      Chi(2) and t tests were used to assess relationships between underreporting and
      sociodemographic and physiologic factors. Mean ratio of energy intake to resting
      metabolic rate was 1.46 (+/-0.4). Using a lower limit of 1.35, the prevalence of
      underreporting was 46.8%. Underreporting was significantly associated with body
      mass index (P< or =0.001) and waist circumference (P<0.001). Use of this combined
      dietary recall and modified food frequency questionnaire might, therefore,
      provide more accurate dietary assessment in this population. Additional
      modification and validity testing is warranted in this and other populations.

PMID- 17197280
TI  - Changes in public attitudes toward breastfeeding in the United States, 1999-2003.
AB  - Data from the HealthStyles survey, an annual national mail survey to US adults,
      were examined to understand changes in public attitudes toward breastfeeding. The
      1999 and 2003 HealthStyles surveys included four breastfeeding items related to
      public attitudes toward breastfeeding in public and toward differences between
      infant formula and breastmilk. The percentage of respondents in agreement with
      the statement, "Infant formula is as good as breastmilk," increased significantly
      from 14.3% in 1999 to 25.7% in 2003. The increase was particularly large among
      people of low socioeconomic status. The percentage increase in agreement that
      "feeding a baby formula instead of breastmilk increases the chances the baby will
      get sick" grew at a statistically significant level, but the total change was
      small (2.7 percentage points). No significant total changes were found for the
      other two survey items. The perception that infant formula is as good as
      breastmilk would be expected to soften a woman's commitment to breastfeeding
      should she be faced with obstacles to doing so. The findings underscore the need
      to educate the general public that breastfeeding is the best method of feeding
      and nurturing infants. Pediatricians and other health professionals should
      recommend human milk for all infants for whom breastfeeding is not specifically
      contraindicated.

PMID- 17197279
TI  - Financial incentive for diet recall accuracy does not affect reported energy
      intake or number of underreporters in a sample of overweight females.
AB  - Underreporting of energy intake in diet recalls is common, especially among obese
      individuals. Incentives have been used to ameliorate the problem, but are
      typically provided without efficacy assessment. The present study sought to
      determine whether financial incentives decrease underreporting in diet recalls.
      Three groups were used to assess incentive timing effects in this parallel group
      crossover study. One group received a $50 bonus for accurate diet recalls on the
      first two of four recalls. Accuracy was purportedly verified by salivary
      analysis. Another group received the $50 bonus for the last two recalls. A third
      group received no incentive. Mean energy intake during the first two visits was
      compared to mean energy intake during the last two visits to assess differences
      resulting from the incentive. Underreporters were identified using a Goldberg
      cutoff and energy intake <76% of estimated energy expenditure. Energy intake did
      not differ within or between groups at any time, and the number of underreporters
      was not associated with group at any time. Overall, the incentive was ineffective
      in this small, homogeneous sample. Future studies should assess different forms
      of incentives, other study populations, and the probability of incentives causing
      undereating.

PMID- 17197281
TI  - Zinc, iron, and lead: relations to head start children's cognitive scores and
      teachers' ratings of behavior.
AB  - The objective of this study was to conduct a preliminary investigation of lead,
      zinc, and iron levels in relation to child cognition and behavior in a small
      sample of Head Start children. The design was cross-sectional and correlational.
      Participants were 42 3- to 5-year-old children attending rural Head Start
      centers. Nonfasting blood samples of whole blood lead, plasma zinc, and ferritin
      were collected. Teachers rated children's behavior on the California Preschool
      Social Competency Scale, Howes' Sociability subscale, and the Preschool Behavior
      Questionnaire. Children were tested individually with the McCarthy Scales of
      Children's Abilities. Hierarchical regression analyses revealed that zinc and
      ferritin jointly explained 25% of the variance in McCarthy Scales of Children's
      Abilities verbal scores. Lead levels explained 25% of the variance in teacher
      ratings of girls' sociability and 20% of the variance in teacher ratings of
      girls' classroom competence. Zinc levels explained 39% of the variance in teacher
      ratings of boys' anxiety. Univariate analysis of variance revealed that the four
      children low in zinc and iron had significantly higher blood lead (median=0.23
      micromol/L [4.73 microg/dL]) than the 31 children sufficient in zinc or iron
      (median=0.07 micromol/L [1.54 microg/dL]) or the 7 children sufficient in both
      (median=0.12 micromol/L [2.52 microg/dL]), suggesting an interaction among the
      three minerals. Within this small low-income sample, the results imply both
      separate and interacting effects of iron, zinc, and lead. They underscore the
      importance of studying these three minerals in larger samples of low-income
      preschool children to make more definitive conclusions.

PMID- 17197283
TI  - What are the latest figures for state-specific prevalence of obesity in the
      United States?

PMID- 17197284
TI  - Effects of photodynamic therapy using 5-aminolevulinic acid on cultured human
      adenomyosis-derived cells.
AB  - OBJECTIVE: To evaluate the potential of photodynamic therapy with aminolevulinic
      acid (ALA) on human adenomyosis-derived cells compared with endometrial stromal
      cells. DESIGN: In vitro study. SETTING: Department of Obstetrics and Gynecology,
      Tohoku University Hospital. PATIENT(S): Women with adenomyosis attending the
      University hospital. INTERVENTION(S): Photodynamic treatment. MAIN OUTCOME
      MEASURE(S): Cell survival rates. RESULT(S): Treatment with both ALA and
      irradiation caused significantly decreased survival of cells derived from human
      adenomyosis compared with ALA or irradiation alone. The combination of
      irradiation and ALA led to 79.3%, 68.0%, and 59.5% cell survival at 1.6, 4, and 8
      J/cm2, respectively, whereas ALA and irradiation alone caused 92.8% and 97%
      survival, respectively. CONCLUSION(S): Photodynamic therapy using ALA caused
      extensive death of cells derived from human adenomyosis. Photodynamic treatment
      using ALA may be a new treatment for patients with adenomyosis uteri in the
      future.

PMID- 17197285
TI  - Outcome of in vitro fertilization in women 45 years and older who use autologous
      oocytes.
AB  - OBJECTIVE: To determine the IVF outcome in women over the age of 44 years.
      DESIGN: Retrospective analysis. SETTING: University-based IVF center. PATIENT(S):
      Two hundred eighty-eight consecutive IVF cycles in women over the age of 44
      years. INTERVENTION(S): IVF. MAIN OUTCOME MEASURE(S): Ovarian response and cycle
      outcome. RESULTS: The mean age of the patients was 45.4 (+/-0.73) years, with a
      range of 45-49 years. Fifty-seven of 288 (19.8%) did not start because of an
      elevated FSH or ovarian cyst. Just over 30% (70/231) had their cycle cancelled
      before retrieval. The mean number of oocytes was 6.8 (+/-3.8), and the mean
      number of fertilized zygotes was 5.4 (+/-3.4). On average, the mean numbers of
      embryos replaced were 3.2 (+/-1.5). An overall pregnancy rate of 21.1% (34/161)
      per retrieval was found. Of these, 85.3% (29/34) experienced a pregnancy loss.
      The overall delivery rate was 3.1% (5/161) per retrieval. Only patients at 45
      years of age with a good response (>5 oocytes) achieved a delivery.
      CONCLUSION(S): We have shown that IVF is a reasonable option for women of very
      advanced maternal age (>44 years) but is limited to those at the age of 45 years
      with a response of >5 oocytes.

PMID- 17197286
TI  - Favorable influence of local injury to the endometrium in intracytoplasmic sperm
      injection patients with high-order implantation failure.
AB  - Local injury to the endometrium prior to controlled ovarian stimulation may
      considerably improve implantation rates and pregnancy outcomes in
      intracytoplasmic sperm injection patients with high-order implantation failure (>
      or =4 IVF trials and > or =12 transferred embryos).

PMID- 17197287
TI  - Heat-induced antigen retrieval: mechanisms and application to histochemistry.
AB  - Since the introduction of the fluorescence-labeled antibody method by Coons et
      al. [Immunological properties of antibody containing a fluorescent group. Proc
      Soc Exp Biol Med 47, 200-2002], many immunohistochemical methods have been
      refined to obtain high sensitivity with low background staining at both light and
      electron microscopic levels. Heat-induced antigen retrieval (HIAR) reported by
      Shi et al. in the early 1990s has greatly contributed to immunohistochemical
      analysis for formalin-fixed and paraffin-embedded (FFPE) materials, particularly
      in the field of pathology. Although antigen retrieval techniques including enzyme
      digestion, treatment with protein denaturants and heating have been considered
      tricky and mysterious techniques, the mechanisms of HIAR have been rapidly
      elucidated. Heating cleaves crosslinks (methylene bridges) and add methylol
      groups in formaldehyde-fixed proteins and nucleic acids and extends polypeptides
      to unmask epitopes hidden in the inner portion of antigens or covered by adjacent
      macromolecules. In buffers having an appropriate pH and ion concentration,
      epitopes are exposed without entangling the extended polypeptides during cooling
      process, since polypeptides may strike a balance between hydrophobic attraction
      force and electrostatic repulsion force. Recent studies have demonstrated that
      HIAR is applicable for immunohistochemistry with various kinds of specimens,
      i.e., FFPE materials, frozen sections, plastic-embedded specimens, and physically
      fixed tissues at both the light- and electron-microscopic levels, and have
      suggested that the mechanism of HIAR is common to aldehyde-fixed and aldehyde
      unfixed materials. Furthermore, heating has been shown to be effective for flow
      cytometry, nucleic acid histochemistry (fluorescein in situ hybridization (FISH),
      in situ hybridization (ISH), and terminal deoxynucleotidyl transferase-mediated
      nick labeling (TUNEL)), and extraction and analysis of macromolecules in both
      FFPE archive materials and specimens processed by other procedures. In this
      article, we review mechanism of HIAR and application of heating in both
      immunohistochemistry and other histochemical reactions.

PMID- 17197289
TI  - Idiopathic ventricular tachycardia: Diagnosis and management.
AB  - Idiopathic ventricular tachycardia (VT) is an uncommon form of VT that is seen in
      patients without structural heart disease. It is commonly seen in young patients
      and usually has a benign course. Recent studies have delineated the mechanisms
      and anatomical locations of this form of VT. Recognition of various forms of
      idiopathic VT based on characteristic QRS morphology from the 12-lead
      electrocardiogram (ECG) has important prognostic and therapeutic implications.
      The understanding of the mechanisms of idiopathic VT has led to the use of
      specific antiarrhythmic drugs targeting particular arrhythmias. Recent
      technological advances in the field of mapping and catheter ablation have led to
      a suitable alternative to drug therapy with a very high cure rate. This review
      describes the clinical features, ECG recognition, and management of idiopathic
      monomorphic VT.

PMID- 17197291
TI  - Opposition to the use of lidocaine in rapid sequence intubation.

PMID- 17197290
TI  - In defense of the use of lidocaine in rapid sequence intubation.

PMID- 17197292
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Varicella outbreak among vaccinated children--Nebraska, 2004.

PMID- 17197293
TI  - It's a dog's life.

PMID- 17197294
TI  - Radiation risk associated with computed tomography and high frequency emergency
      department users.

PMID- 17197295
TI  - Craniofacial high-pressure air injection injury.

PMID- 17197296
TI  - "Toxic shock:" can playground static cause insulin pump failure?

PMID- 17197297
TI  - Is the answer to Dr. Green's question: "Emergency medicine trauma specialists"?

PMID- 17197298
TI  - Lap dancer's lament: an occupational hazard related to community-associated
      methicillin-resistant Staphylococcus aureus.

PMID- 17197300
TI  - Images in emergency medicine. Traumatic pneumatocele.

PMID- 17197301
TI  - Minimum 10-year results of a tapered, titanium, hydroxyapatite-coated hip stem:
      an independent review.
AB  - The performance of, and periprosthetic bone response to, a tapered, titanium
      (Ti6Al4V), hydroxyapatite-coated femoral hip prosthesis was evaluated at minimum
      of 10 years of follow-up. Data were prospectively collected on 147 consecutive
      primary hip arthroplasties performed in 133 patients by a single surgeon during a
      2-year interval. Clinical and radiographic analyses of 96 hips in 86 patients
      were independently performed by 2 surgeons who were not involved in the care of
      these patients. There were no cases of aseptic loosening of the femoral
      component. Subsidence and stress shielding occurred in 5% and 2% of cases,
      respectively, and was not clinically significant. In all 15 hips that required
      revision of the acetabular component, the femoral component was found to be well
      fixed, without any occurrence of distal osteolysis. This femoral design provided
      reliable osseointegration that was durable at a mean of 11.5 years of follow-up.

PMID- 17197303
TI  - The significance of metal staining on alumina femoral heads in total hip
      arthroplasty.
AB  - Metallic transfer to alumina can occur intraoperatively and while reducing a
      dislocated total hip, when the femoral head contacts the rim of the metal
      acetabular shell. To see if metal discoloration is associated with changes to the
      alumina, we examined 14 metal-stained alumina femoral heads retrieved from
      ceramic-on-ceramic articulations using electron microscopy and noncontact
      profilometry. Metal staining was associated with surface damage to alumina on the
      femoral heads removed from unstable total hips. The surface roughness of metal
      stained alumina heads was significantly greater than that of unused alumina
      heads. Alumina femoral heads should be protected against contact with the metal
      cup during total hip implantation. Dislocations in ceramic-on-ceramic total hips
      should be addressed early because of possible damage to the surface.

PMID- 17197302
TI  - Clinical experience using a minimally invasive surgical approach for total knee
      arthroplasty: early results of a prospective randomized study compared to a
      standard approach.
AB  - There has been recent attention concerning minimally invasive techniques for knee
      arthroplasty. It is not clear whether these complicated techniques can be
      reproduced across multiple centers and for all surgeons. This prospective,
      randomized, multicenter study was carried out to assess safety and efficacy of a
      minimally invasive total knee arthroplasty. The study consisted of 80 knees.
      There were no differences in blood loss, operative time for completion of
      surgery, infection, and ultimate wound healing. There were 4 knees with delayed
      wound healing in the minimally invasive surgical technique group versus 1 in the
      standard group, which did not affect outcome. Early clinical and radiographic
      results were also indistinguishable. At 12 weeks follow-up, there was no
      difference in mean Knee Society objective and functional scores. In summary, in
      this study, minimal incision total knee arthroplasty demonstrated no improvement
      over a standard approach.

PMID- 17197304
TI  - Minimal incision protocols for anesthesia, pain management, and physical therapy
      with standard incisions in hip and knee arthroplasties: the effect on early
      outcomes.
AB  - Dramatic early outcomes with "minimal incision" surgery are attributed to patient
      selection, perioperative management, and the surgical procedure. This study was
      one on 50 patients in a single surgeon's practice who underwent total hip and
      total knee arthroplasties with standard incisions. The first 25 patients had
      standard perioperative management, whereas the second 25 had the anesthesia, pain
      management, and physical therapy protocols described for minimal incision
      surgery. A dramatic reduction in the time it took to achieve the goals for
      discharge was observed in the second group. Most patients with the "mini"
      protocols were ready for discharge within 24 hours. The implications of these
      results are discussed.

PMID- 17197305
TI  - Porous tantalum implant in early osteonecrosis of the hip: preliminary report on
      operative, survival, and outcomes results.
AB  - Porous tantalum implants are used in early osteonecrosis of the hip. Device
      evaluation included surgical time, blood loss, hospitalization, patient
      controlled analgesia use, transfusions, implant survival, and outcomes. Mean
      blood loss was 70 mL. Mean operative time was 36 minutes. Average hospitalization
      was less than 1 day. No patient required patient-controlled analgesia use or
      transfusions. Results were compared to a historical vascularized fibular graft
      population. All parameters were less than the fibular graft groups (P < .00001).
      All surviving implants (86%) resulted in good to excellent outcomes. Kaplan-Meier
      analysis at 39 months was 86% and 67% for the implant and fibular graft,
      respectively (P = .21). Early outcomes demonstrate that porous tantalum implants
      are a safe option for femoral head salvage. Continued follow-up is necessary to
      determine the long-term success.

PMID- 17197306
TI  - Results on total hip arthroplasties with femoral shortening for Crowe's group IV
      dislocated hips.
AB  - We performed total hip arthroplasties in 11 women with Crowe's group IV
      completely dislocated hips, with a mean age at surgery of 59.6 years and a mean
      follow-up of 65 months. In all cases, femoral shortening was achieved using step
      cut osteotomy. All acetabular cups were placed in their anatomical locations. The
      mean Merle d'Aubigne hip score improved from 10.9 points to 16.9. There was no
      case of nonunion or malunion in the osteotomized site. Temporary numbness was
      observed in 2 hips, which subsided within 3 weeks without any treatment. One hip
      had to be revised 8 years after surgery because of aseptic loosening of the stem.
      Our study shows that total hip arthroplasty, incorporating step-cut femoral
      shortening, provides acceptable results for completely dislocated hip.

PMID- 17197307
TI  - Activity level in young patients with primary total hip arthroplasty: a 5-year
      minimum follow-up.
AB  - Increased activity level after total hip arthroplasty (THA) is considered a risk
      factor for early prosthetic failure in young patients. Forty-one primary total
      hip arthroplasties in 34 patients were evaluated. Walking activity was measured
      using a pedometer to record gait cycles. Patients completed a University of
      California, Los Angeles (UCLA) activity questionnaire. Linear wear rates were
      measured. Mean ages at surgery and final follow-up were 42 and 50.3 years,
      respectively (mean gait cycles per year, 1.2 million; mean UCLA score, 6; mean
      linear wear, 0.16 mm/y). Increased body mass index and age correlated with
      decreased gait cycles per year. Patients with systemic disease were less active
      than patients with localized hip conditions. Femoral head diameter was a
      predictor of linear wear. The average gait cycles per year and wear rate for this
      population do not appear accelerated relative to average values reported in older
      populations.

PMID- 17197308
TI  - Comparison of the 2-incision and mini-incision posterior total hip arthroplasty
      technique: a retrospective match-pair controlled study.
AB  - We compared the outcomes of the mini-posterior and 2-incision total hip
      arthroplasty approaches by analyzing 43 matched pairs of patients. The following
      outcomes were evaluated: (1) Harris Hip Score, (2) Medical Outcomes Study 36-Item
      Short-Form Health Survey, (3) the Medical Outcomes Study Sleep Scale, and (4) the
      Western Ontario and McMaster Osteoarthritis Index. Function was regained earlier
      by patients having the 2-incision total hip arthroplasty as determined by length
      of hospitalization (P = .002) and multiple return to function parameters,
      although this may be the result of hip precautions placed on the posterior group.
      Posterior mini-incision patients had less operating time (P < .0001) and blood
      loss (P = .001). Complications did not differ between surgical techniques. No
      patients were revised. The 2-incision operation was better for function and
      length of stay, and the posterior mini-incision was easier to perform, although
      these groups used different selection criteria.

PMID- 17197309
TI  - Tight fit technique in primary hybrid total hip arthroplasty for patients with
      hip dysplasia.
AB  - This article presents the midterm results of hybrid total hip arthroplasty for
      patients with hip dysplasia by use of a tight fit technique for the femoral
      component. We followed up 113 hips in 99 patients for a mean of 11 years. All
      final femoral rasps used in this study overrasped by 0.5 to 1.0 mm for stem
      insertion, resulting in relatively thin cement mantles. Both components of one
      hip were removed because of infection. The other 5 acetabular components were
      revised for osteolysis, recurrent dislocation, or dislodgement of the
      polyethylene liner. No femoral component was revised for aseptic loosening. We
      conclude that the tight fit technique using a canal-filling stem may produce good
      long-term results for patients with hip dysplasia.

PMID- 17197310
TI  - The effects of a prospective case payment system on hospital charges for total
      hip arthroplasty in Taiwan.
AB  - We evaluate the effects of instituting prospective case payment system (PPS)
      system on total hip arthroplasty (THA) charges and compare our university
      hospital THA cost structure with comparable health care institutions in the
      United States. The study consisted of 5009 patients who received a primary THA in
      24 hospitals between 1995 and 2001. After adjusting for inflation, the average
      total charge of THA for pre-PPS was 4762 US dollars and 4054 US dollars for post
      PPS. The average cost for prostheses accounted for 61% of total costs at our
      hospital, as compared with the US studies ranging from 27% to 34%. As United
      States, PPS achieved the purpose of cost containment and changed practice
      patterns of orthopedic surgeons and hospital resource use in Taiwan.

PMID- 17197311
TI  - Cementless two-stage exchange arthroplasty for infection after total hip
      arthroplasty.
AB  - We retrospectively reviewed all patients at one center with an infected total hip
      arthroplasty treated with 2-stage revision using cementless components for the
      second stage and the PROSTALAC articulated spacer at the first stage. Twenty-nine
      patients were reviewed and followed for at least 2 years postoperatively. An
      isolated Staphylococcus species was cultured in 76% (22/29) of patients. Three
      (10.3%) of 29 patients had recurrent infection at the site of the prosthesis. One
      of the 3 patients ultimately underwent a Girdlestone arthroplasty. Another
      patient was managed with irrigation and debridement, whereas the final patient
      was treated with intravenous antibiotics alone. Treatment of infection at the
      site of a hip arthroplasty with 2-stage revision using cementless components and
      an articulated spacer yields recurrence rates similar to revisions where at least
      one of the components at the second stage is fixed with antibiotic-loaded cement.

PMID- 17197312
TI  - Ultimate outcome in immediate postoperative total hip arthroplasty instability.
AB  - The objective of this study was to determine the ultimate outcome of patients who
      experienced immediate postoperative instability after primary total hip
      arthroplasty using regional anesthesia. Thirty-one patients whose radiographs
      demonstrated dislocation or subluxation immediately after total hip arthroplasty
      were evaluated as to the ultimate outcome of hip function and stability. Once a
      dislocation has occurred, the risk of redislocation is high. In this study, of
      the 29 patients who did not have revisions immediately after surgery, 3 (10.3%)
      have had recurrent dislocation and 1 (3.5%) has had a subluxation event.
      Recurrent instability or the need for revision surgery is significantly greater
      when compared with those patients who have no evidence of postoperative
      instability.

PMID- 17197313
TI  - Strength and voluntary activation of quadriceps femoris muscle in total knee
      arthroplasty with midvastus and subvastus approaches.
AB  - To determine and compare the influence of 2 different approaches on quadriceps
      femoris muscle function in total knee arthroplasty (TKA), 20 patients (14 women,
      6 men) with bilateral knee osteoarthritis underwent a 1-stage bilateral TKA.
      Surgical approaches (subvastus, midvastus) were performed by a random selection.
      Measurements of quadriceps voluntary activation and maximal voluntary contraction
      were estimated by a twitch interpolation technique before, 3 and 6 months after
      TKA. Knee pain was quantified by the Lewis Score. There was no difference between
      the 2 approaches at 3 and 6 months after TKA with regard to maximal voluntary
      contraction (P = 0.84, F = 0.041) and voluntary activation (P = .863, F = 0.031).
      In the subvastus group was a significantly higher knee pain until 6 months after
      surgery (P = .02). The subvastus approach for TKA does not provide any advantages
      compared with the midvastus approach with respect to the quadriceps femoris
      muscle strength in the early postoperative period. Furthermore, the subvastus
      approach caused significantly more pain postoperatively.

PMID- 17197314
TI  - Graft incorporation after acetabular and femoral impaction grafting with washed
      irradiated allograft and autologous marrow.
AB  - Rates of around 40% incorporation have been described when chips of irradiated
      cancellous allograft with retained fat were impacted with the Exeter technique.
      We report the results of acetabular and femoral impaction bone grafting during
      revision hip arthroplasty using washed irradiated allograft with autologous
      marrow. Eighty-five consecutive patients underwent acetabular and or femoral
      revision arthroplasty. Evidence of graft cortication and trabeculation was
      recorded on successive postoperative radiographs, over a mean period of 44
      months. Ninety-six percent (49/51) and 90% (53/59) of patients showed
      incorporation in acetabular and femoral grafts, respectively. This was usually
      apparent by 6 months postoperatively. We conclude that the addition of autologous
      marrow to irradiated bone allograft during impaction grafting is a cheap and
      highly effective way of achieving graft incorporation.

PMID- 17197315
TI  - How much sterile saline should be used for efficient lavage during total knee
      arthroplasty? Effects of pulse lavage irrigation on removal of bone and cement
      debris.
AB  - Bone and polymethyl methacrylate (PMMA) debris particles generated during total
      knee arthroplasty (TKA) reportedly cause third-body wear. The present study
      investigated the volume of pulse lavage sufficient for removal of intraoperative
      PMMA and bone particles. Subjects comprised 8 patients who underwent cemented
      TKA. Pulse lavage with 8 L of sterile saline was performed using a pulsatile
      irrigator. During pulse lavage, aspirated fluid was collected in a 1-L aliquot,
      and the number and size of bone and PMMA particles in each fluid were measured.
      Image analysis revealed that the number of particles peaked at first lavage and
      gradually decreased until eighth lavage. Significant differences were found
      between the first vs second, second vs third, and third vs fourth lavage.
      However, no significant differences were found beyond the fourth lavage. This
      study indicated that 4 L of pulse lavage is effective for removing the particles
      during cemented TKA.

PMID- 17197316
TI  - Gait analysis of patients with resurfacing hip arthroplasty compared with hip
      osteoarthritis and standard total hip arthroplasty.
AB  - Patients with standard total hip arthroplasties may have reduced hip abduction
      and extension moments when compared with normal nonosteoarthritic hips. In
      comparison, patients after resurfacing total hip arthroplasty appear to have a
      near-normal gait. The authors evaluated temporal-spatial parameters, hip
      kinematics, and kinetics in hip resurfacing patients compared with patients with
      unilateral osteoarthritic hips and unilateral standard total hip arthroplasties.
      Patients with resurfacing walked faster (average 1.26 m/s) and were comparable
      with normals. There were no significant differences in hip abductor and extensor
      moments of patients with resurfacing compared with patients in the standard hip
      arthroplasty group. This study showed more normal hip kinematics and
      functionality in resurfacing hip arthroplasty, which may be due to the large
      femoral head.

PMID- 17197317
TI  - The role of cement viscosity on cement-bone apposition and strength: an in vitro
      model with medullary bleeding.
AB  - We compared the mechanical and morphological characteristics of cement-bone
      structures created with either standard- or low-viscosity cement using a human
      cadaver model that simulated intramedullary bleeding. The goal is to determine if
      the viscosity of the cement would affect the strength of the cement-bone
      interface and the degree of apposition between the cement and bone. The tensile
      strength of cement-bone constructs with standard-viscosity cement (2.42 +/- 1.55
      MPa) was 21% stronger than with low-viscosity cement (2.00 +/- 1.51 MPa, P =
      .034). Cement-bone apposition was positively correlated (r2 = 0.29, P <. 0001)
      with the strength of the interface. There was 15% greater apposition between
      cement and bone (P = .036) for standard-viscosity cement. Low-viscosity cement
      may be less effective in displacing bone marrow and in preventing hemodynamic
      backflow, resulting in less apposition and a weaker interface.

PMID- 17197318
TI  - In vivo sagittal plane kinematics of the Avon patellofemoral arthroplasty.
AB  - Isolated patellofemoral osteoarthritis can be treated with patellofemoral
      arthroplasty (PFA). In contrast to total knee arthroplasty, the effect of PFA on
      knee joint kinematics is not known. A study was performed to identify the
      kinematic changes after PFA. The sagittal plane kinematics was examined in 12
      patients who had undergone Avon PFA. An established fluoroscopic method was used
      to examine the patellar tendon angle (PTA)/knee flexion relationship during
      functional activities. No significant difference existed between the kinematics
      of PFA knees compared with normal, except for a uniform elevation in PTA
      throughout the range. This increase in PTA in the PFA joint represents a 1.6-mm
      anterior displacement of the patella. The kinematic profile after PFA is close to
      normal and suggests that the knee is exhibiting more normal loading
      characteristics than those of the total knee arthroplasty joint.

PMID- 17197319
TI  - Neurovascular injuries in acetabular reconstruction cage surgery: an anatomical
      study.
AB  - Acetabular reconstruction cages are indicated for severe combined segmental and
      cavitary acetabular bone defects. The purpose of this study was to evaluate the
      implications of screw placement and drill plunge and the potential insult to
      anatomical structures when implanting acetabular reconstruction cages. A
      segmental cavitary defect was reamed into the acetabulum and a cage was implanted
      in each of the 10 hemipelvises. The relative course of the superior gluteal
      neurovascular bundle was mapped to assess dissection intervals. When cage screws
      were placed at least 15 mm longer than needed, 13% and 20% of screws of the
      superior flange and anterior rim hit the femoral nerve, respectively, and
      approximately 60% of the screws placed in the posterior rim endangered the
      obturator nerve. A "safe zone" for screw size may be a 15- and 25-mm screw for
      the superior flange and posterior rim, respectively.

PMID- 17197320
TI  - Use of an intramedullary nail for correction of femoral deformities combined with
      total knee arthroplasty: a technical tip.
AB  - Simultaneous femoral deformity correction combined with total knee arthroplasty
      can be a complex procedure, which can be simplified with this described
      technique. A femoral component that allows access to the intramedullary canal is
      necessary to be able to use this technique.

PMID- 17197321
TI  - Delayed fracture of a ceramic insert with modern ceramic total hip replacement.
AB  - We report a case of ceramic liner fracture in a 34-year-old man that occurred 1
      year 9 months after total hip arthroplasty with a BiCONTACT (Aesculap,
      Tuttlingen, Germany) ceramic-on-ceramic prosthesis. The ceramic liner was found
      within the metal shell in 4 large pieces and multiple small fragments in the
      peripheral portions. Its condition indicated that the possible mechanism of late
      ceramic liner chip fracture was repeated episodes of impingement between the
      prosthetic neck and the edge of the ceramic liner. Squatting, kneeling, and
      sitting cross-legged caused impingement. These positions are more common in Asian
      populations than in Western populations. After the joint was thoroughly
      irrigated, a new modular ceramic liner and a 28-mm ceramic head were implanted.

PMID- 17197322
TI  - Dissociation of the modular femoral stem from the metaphyseal sleeve during
      reduction of a total hip arthroplasty dislocation.
AB  - Dissociation of components in a modular total hip arthroplasty system has been
      described. We describe the case of dissociation at the interface between the
      femoral stem and the proximal metaphyseal sleeve during attempts to reduce a
      dislocation. Open reduction was required for successful treatment of this rare
      complication.

PMID- 17197323
TI  - Catastrophic failure of a modular revision total hip polyethylene insert.
AB  - Early catastrophic failure of a modular polyethylene component is a potential
      problem after revision total hip arthroplasty. We describe an unusual case of
      polyethylene failure that occurred within 18 months of implantation in which no
      obvious technical error or mechanical failure was identified. The acetabular
      polyethylene insert was prepared with gas plasma sterilization, and the shelf
      life was 4 months. Radiographic evaluation used generalized Hough transforms to
      assess the cup articulation. We identified cup penetration of 2.8 mm before
      revision and catastrophic destruction of the polyethylene liner at the time of
      revision. Possible factors implicated for failure included a thin polyethylene
      liner, increased hip separation, femoral head mismatch, and the high activity
      level of a younger patient. We believe that this case report highlights the need
      for future investigations of these subtle factors.

PMID- 17197324
TI  - Medial tibial plateau fracture complicating unicompartmental knee arthroplasty.
AB  - We describe a new cause of a medial tibial plateau fracture complicating the
      early postoperative rehabilitation following unicompartmental knee arthroplasty.
      The patient was successfully treated by open reduction and internal fixation by
      buttress plating the fracture and retaining the prosthesis. The treatment option
      used proved to be successful, although careful patient selection for
      unicompartmental knee arthroplasty should be recommended to decrease the risk of
      this complication.

PMID- 17197325
TI  - It's Not Just About the Spine: North American Spine Society Presidential Address,
      Seattle, Washington, 2006.

PMID- 17197326
TI  - Incidence of contraindications to total disc arthroplasty: a retrospective review
      of 100 consecutive fusion patients with a specific analysis of facet arthrosis.
AB  - BACKGROUND CONTEXT: The role of total disc arthroplasty (TDA) in the treatment of
      spinal pathology is unclear. TDA has been touted as an alternative to fusion.
      However, not all back pain is purely discogenic in origin. Contraindications to
      TDA exist. At Spine Week in Porto, Portugal, Cammisa's group from the Hospital
      for Special Surgery in New York presented a series of 56 fusions where 100% of
      patients had one or more of 10 contraindications to TDA. En face, this appears to
      be an extremely large number. PURPOSE: The purpose of the study was to repeat the
      Hospital for Special Surgery study in another cohort of fusion patients. STUDY
      DESIGN/SETTING: This study was an independent, retrospective record review of 100
      consecutive lumbar spinal fusions performed at a tertiary care private medical
      center. PATIENT SAMPLE: All adult patients having primary1-3 level lumbar spinal
      fusions from January 2003 to May 2004 were assessed. OUTCOME MEASURES:
      Physiologic measures included imaging, range of motion, and response to facet
      blocks. METHODS: A retrospective chart review was performed of 100 consecutive
      patients having primary 1-3 level lumbar fusion by all five active staff spinal
      surgeons (3 orthopedic and 2 neurosurgeons). The review was performed
      independently by the doctorate level physiotherapist who serves as the medical
      center's research coordinator, reporting to the chairman of the Hospital
      institutional review board. The same 10 contraindications from Cammisa's study
      were noted. Additional facet arthrosis data were collected, including mention on
      imaging reports or operating room notes. Clinical notes were reviewed for
      documentation of range of lumbar motion (ROM) and whether there was restricted or
      painful extension ROM. Note was made if patients had facet blocks as another
      clinical indicator of facet arthrosis. RESULTS: All 100 patients had at least one
      contraindication to TDA. The average was 3.69 (range 1-7). Only one patient had
      facet arthrosis as their only contraindication. Facet arthrosis was documented on
      imaging reports or operating room notes in 97/100. Reduced extension was present
      in 71/75 charts that documented ROM. Facet blocks were performed in 12/100 and
      gave greater than 50% relief in nine. CONCLUSIONS: Both our study and Cammisa's
      indicate that all lumbar fusion patients in our two institutions have at least
      one contraindication to TDA. The average fusion patient does not appear to have
      isolated discogenic pain. A large proportion of the patients appeared to have
      facet arthritis. The point where facet arthrosis definitely constitutes a
      contradiction to TDA will require analysis during long-term arthroplasty follow
      up studies. Suitable patients for TDA may not represent a significant cohort
      presently undergoing lumbar fusion.

PMID- 17197327
TI  - Polyethylene wear and rim fracture in total disc arthroplasty.
AB  - BACKGROUND CONTEXT: Polyethylene (PE) has been used in total disc replacements
      (TDRs) in Europe since the 1980s. However, the extent of surface damage of PE,
      including rim fracture and wear, after long-term implantation remains poorly
      understood. PURPOSE: The purpose of this study was to evaluate the magnitude and
      rate of PE wear and surface damage in TDRs. STUDY DESIGN: TDR components were
      retrieved from patients undergoing revision TDR surgery and conversion to fusion.
      PATIENT SAMPLE: Twenty-one implants (SB Charite III; DePuy Spine, Raynham, MA)
      were analyzed from 18 patients (12 female, 6 male) undergoing TDR revision
      surgery. The components were implanted between 1.8 and 16.0 years (average: 7.8
      years) at L2-L3 (n=1), L3-L4 (n=1), L4-L5 (n=11), and L5-S1 (n=8). They were
      removed due to pain (in all cases) and were associated with subsidence (n=6),
      anterior migration (n=2), core dislocation (n=2), lateral subluxation (n=1), wear
      with wire marker fracture (n=1), end plate loosening (n=2), and osteolysis (n=1).
      OUTCOME MEASURES: Clinical information was collected from medical records and
      radiographs. Retrieval analysis included dimensional measurements and assessment
      of the extent and severity of PE surface damage mechanisms. METHODS: MicroCT
      scanning was used to identify the presence of internal cracks in the PE core and
      to scan the geometry of the retrievals. Light microscopy, coupled with white
      light interferometry, was used to evaluate the surface damage mechanisms at the
      dome and rim. RESULTS: The dominant wear mechanism was adhesive/abrasive wear at
      both the dome and rim. End plate penetration (dome wear) ranged from 0.1 to 0.9
      mm (average: 0.3 mm), and was correlated with implantation time (Spearman's
      rho=0.48, p=.03). There was also evidence of macroscopic rim damage, including
      radial and transverse cracking, fracture, plastic deformation, and third-body
      damage. End plate penetration measured at the rims ranged from 0.02 to 0.8 mm
      (average: 0.3 mm). Cracks in the core were oriented transversely in 11 of 21
      implants (52%), and radially around the rim in 11 of 21 implants (52%).
      Radiographic wire marker fracture, observed in 9 of 21 implants (43%), was always
      associated with deformation, cracking, or fracture of the PE rim. In two cases, a
      fractured wire marker became lodged in the articulating surface between the PE
      and the metallic end plate. CONCLUSIONS: This is the first study to
      quantitatively analyze the long-term PE damage mechanisms in contemporary TDRs.
      The TDRs displayed surface damage observed previously in both hip and knee
      replacements. Because of the evidence of increasing wear with implantation time,
      along with the demonstrated potential for osteolysis in the spine, regular long
      term follow-up for patients undergoing TDRs is warranted.

PMID- 17197328
TI  - The validity of manual examination in assessing patients with neck pain.
AB  - BACKGROUND CONTEXT: Although manual therapists believe that they can diagnose
      symptomatic joints in the neck by manual examination, that conviction is based on
      only one study. That study claimed that manual examination of the neck had 100%
      sensitivity and 100% specificity for diagnosing painful zygapophyseal joints.
      However, the study indicated that its results should be reproduced before they
      could be generalized. PURPOSE: The present study was undertaken to answer the
      call for replication studies. The objective was to determine the sensitivity,
      specificity, and likelihood ratio of manual examination for the diagnosis of
      cervical zygapophyseal joint pain. STUDY DESIGN: The study was conducted in a
      private practice located in a rural town. The practice specialized in
      musculoskeletal pain problems. PATIENT SAMPLE: The study sample was 173 patients
      with neck pain in whom cervical zygapophyseal joint pain was suspected on
      clinical examination, and who were willing to undergo controlled diagnostic
      blocks of the suspected joint or joints. OUTCOME MEASURES: The validity of manual
      diagnosis was determined by calculating its sensitivity, specificity, and
      positive likelihood ratio. METHODS: Patients who exhibited the putatively
      diagnostic physical signs of cervical zygapophyseal joint pain were referred to a
      radiologist who performed controlled, diagnostic blocks of the suspected joint,
      and other joints if indicated. The results of the blocks constituted the
      criterion standard, against which the clinical diagnosis was compared, by
      creating contingency tables. RESULTS: Manual examination had a high sensitivity
      for cervical zygapophyseal joint pain, at the segmental levels commonly
      symptomatic, but its specificity was poor. Likelihood ratios barely greater than
      1.0 indicated that manual examination lacked validity. Although the results
      obtained were less favorable than those of the previous study, paradoxically they
      were statistically not different. CONCLUSIONS: The present study found manual
      examination of the cervical spine to lack validity for the diagnosis of cervical
      zygapophyseal joint pain. It refutes the conclusion of the one previous study.
      The paradoxical lack of statistical difference between the two studies is
      accounted for by the small sample size of the previous study.

PMID- 17197329
TI  - The pyrite standard: the Midas touch in the diagnosis of axial pain syndromes.

PMID- 17197330
TI  - Correlation of end plate shape on MRI and disc degeneration in surgically treated
      patients with degenerative disc disease and herniated nucleus pulposus.
AB  - BACKGROUND CONTEXT: The sagittal profile of the lumbar end plates on magnetic
      resonance imaging (MRI) has not been investigated in patients with degenerative
      disc disease (DDD) or herniated nucleus pulposus (HNP). PURPOSE: To examine the
      shape of the end plates in patients treated surgically for a) low back pain or b)
      radiculopathy with HNP. Furthermore, to investigate the correlation between end
      plate shape and disc degeneration on the one, and end plate shape and symptoms on
      the other. STUDY DESIGN/SETTING: Retrospective review of charts and radiographs.
      METHODS: The charts, operative reports, preoperative lateral plain radiographs,
      and MRI scans of 178 patients (85 with low back pain and 93 with HNP) were
      reviewed. End plate shape was determined on midsagittal MRI cuts, disc
      degeneration was graded on T2 sequences, and disc height was measured on lateral
      plain radiographs from L1 to S1 in all patients. Student t-test and chi(2) test
      were used to detect significant differences and associations. RESULTS: Flat and
      irregular levels were most common in the lower lumbar spine. The L5/S1 segment
      was flat in most cases, due to a flat sacral end plate. In DDD patients, disc
      degeneration on MRI and plain radiographs worsened from concave to flat, to
      irregular levels. In HNP patients, MRI demonstrated concave levels to be less
      degenerated, whereas no difference was detected between flat and irregular
      levels. Disc height of irregular levels was well preserved in HNP patients.
      Comparing the two groups, flat levels were more degenerated on MRI in HNP
      patients. Despite similar degrees of degeneration on MRI, concave and irregular
      levels in DDD patients had lower disc heights. A higher frequency of symptoms was
      found in flat and irregular levels for both patient groups. CONCLUSIONS: The
      sagittal profile of end plates in the lumbar spine was described for patients
      with DDD on the one and HNP on the other. A higher association with symptoms was
      observed for flat and irregular levels in both patient groups. In DDD patients,
      disck degeneration on both MRI and plain radiographs increased from concave to
      flat, to irregular levels. In HNP patients, MRI demonstrated concave levels to be
      less degenerated, whereas no difference was detected between flat and irregular
      levels. Disc height of irregular levels was well preserved in HNP patients.
      Comparing the two groups of patients, flat levels were more degenerated on MRI in
      HNP patients. Despite similar degrees of degeneration on MRI, concave and
      irregular levels in DDD patients had lower disc heights. The correlation of
      symptoms and disc degeneration with the end plate shapes is not definitive
      evidence of end plate remodeling around degenerated discs. It may simply
      represent the higher rate of disc degeneration in the lower lumbar levels. This
      analysis did not provide any hints as to which degenerated discs are more likely
      to herniated and cause leg symptoms or cause predominantly low back pain.

PMID- 17197331
TI  - Reliability and agreement between fine-cut CT scans and plain radiography in the
      evaluation of posterolateral fusions.
AB  - BACKGROUND CONTEXT: Current imaging techniques used to evaluate fusion status
      after a posterolateral fusion such as radiographs, computed axial tomography (CT)
      scans, and tomograms are known to be inaccurate, with error rates estimated from
      20% to 40%. Previous studies evaluated CT scans using 2-4-mm thick slices with
      limited reconstructions. PURPOSE: The purpose of this study is to determine the
      intraobserver and interobserver agreement of plain radiographs and fine-cut (1
      mm) CT scans with sagittal and coronal reconstructions in evaluating fusion
      status after instrumented posterolateral fusions. The correlation between
      radiographic evaluations and CT scan evaluations was also analyzed. STUDY
      DESIGN/SETTING: Cross-sectional, blinded. PATIENT SAMPLE: One-year radiographs
      and CT scans of 86 patients who had single-level instrumented posterolateral
      fusions. OUTCOME MEASURES: Fusion grades based on previously published criteria
      were determined. METHODS: Three spine surgeons graded the fusions of 86 patients
      who had single-level instrumented posterolateral fusions using 1-year
      postoperative flexion/extension lateral and anteroposterior radiographs, and fine
      cut CT scans with sagittal and coronal reconstructions. The technique used to
      obtain the radiographs and the CT scans was the same in all cases. Two separate
      readings, 2 weeks apart, were done on each patient by each surgeon. The kappa
      coefficients for interobserver and intraobserver variability were determined.
      RESULTS: The intraobserver agreement using CT scans to assess fusion status was
      moderate for both classification systems (Molinari=0.48, Glassman 0.47). The
      intraobserver agreement using X-rays to assess fusion status was fair for the
      Molinari classification (kappa=0.37) and moderate for the Glassman classification
      (kappa=0.43). The interobserver agreement using CT scans to assess fusion status
      was moderate for both classification systems (Molinari=0.48, Glassman 0.48). The
      interobserver agreement using X-rays to assess fusion status was fair for both
      classification systems (Molinari=0.24, Glassman 0.26). Observers agreed most
      often when the fusion was assessed as solid (Molinari k=0.61, Glassman k=0.63).
      The rating on the radiographs and CT scans agreed only 46% to 59% of the time.
      CONCLUSIONS: Fine-cut CT scans with reconstructions have a considerably greater
      degree of interobserver and intraobserver agreement compared with
      flexion/extension and anteroposterior radiographs. Observers agree most often
      when the fusion is assessed as solid. Fusion evaluation based on radiographs
      agrees with CT scans only half the time. Future studies are needed to correlate
      the findings on fine-cut CT scans with surgical exploration.

PMID- 17197332
TI  - Posterolateral lumbar spine fusion with INFUSE bone graft.
AB  - BACKGROUND CONTEXT: INFUSE has been proven effective in conjunction with threaded
      cages and bone dowels for single-level anterior lumbar interbody fusion (ALIF).
      The published experience with posterolateral fusion, although encouraging,
      utilizes a significantly higher dose and concentration of recombinant human bone
      morphogenic protein-2 (rhBMP-2) and a different carrier than the commercially
      available INFUSE. PURPOSE: To present an assessment of fusion rate for
      posterolateral spine fusion with INFUSE Bone Graft. STUDY DESIGN/SETTING:
      Retrospective review of patients treated using INFUSE in posterolateral spine
      fusion in a single institution. PATIENT SAMPLE: 91 patients with minimum 2-year
      follow-up who underwent posterolateral spine fusion using INFUSE as an iliac
      crest bone graft (ICBG) substitute. OUTCOME MEASURES: Fusion rate based on fine
      cut computed tomographic (CT) scans with sagittal and coronal reconstructions.
      METHODS: Fusion was performed using one large INFUSE kit (12 mg rhBMP-2, 1.5
      mg/mL), which was prepared according to the manufacturer's instructions. The
      INFUSE sponge was wrapped around the local bone or graft extender and placed over
      the decorticated surfaces in the lateral gutters. Postoperative CT scans with
      reconstructions were reviewed by two independent orthopedic spine surgeons. CT
      scans of a comparison group of 35 patients who underwent primary single-level
      posterolateral fusion with ICBG were also reviewed. RESULTS: The overall group
      had a mean 4.38 CT fusion grade and a 6.6% nonunion rate. Primary one-level
      fusion cases (n=48) had a mean 4.42 fusion grade a 4.2% nonunion rate. Primary
      multilevel fusions (n=27) had a mean 4.65 CT grade and no nonunions detected.
      Assessment of the 35 primary one-level ICBG control cases demonstrated a mean CT
      grade of 4.35 and a nonunion rate of 11.4%. In the 16 cases of revision for prior
      nonunion, mean CT grade was 3.81 and 4 subjects had nonunions. Additional
      subgroup analysis showed that smokers (n=14) had a mean 4.32 CT grade with no
      nonunions. Men had a mean 4.04 CT grade and an 11.1% nonunion rate compared with
      a mean 4.61 CT grade and 3.6% nonunion rate in women. This difference was
      statistically significant (p=.036). No significant differences in fusion rate
      were observed based upon the specific graft extender used (p=.200). CONCLUSIONS:
      Posterolateral spine fusion involves a more difficult healing environment with a
      limited surface for healing, a gap between transverse processes and the milieu of
      distractive forces. Historically, only ICBG has been able to overcome these
      challenges and reliably generate a successful posterolateral lumbar spine fusion.
      In contrast to prior studies, clinically available INFUSE delivers only 12 mg
      rhBMP-2 at a concentration of 1.5 mg/mL. Despite the lower dose and concentration
      of rhBMP-2, this study suggests that fusion success with INFUSE is equivalent to
      ICBG for posterolateral spine fusion. As with ICBG, development of solid fusion
      or nonunion is a multifactorial process. The use of INFUSE is not a substitute
      for proper surgical technique or optimization of patient-related risk factors.
      Additional studies are needed to determine the incremental benefit of a greater
      rhBMP-2 dose or use of alternative carriers for posterolateral fusion. Finally,
      correlation between radiographic findings and clinical outcomes, and a cost
      benefit analysis are needed. Despite these issues, this study presents compelling
      evidence that commercially available INFUSE is an effective ICBG substitute for
      one- and two-level posterolateral instrumented spine fusion.

PMID- 17197333
TI  - The osteoinductive properties of Nell-1 in a rat spinal fusion model.
AB  - BACKGROUND CONTEXT: Recombinant growth factors bone morphogenetic protein-2 (BMP
      2) and BMP-7 are currently approved for human use but are associated with various
      adverse effects including ectopic bone formation and local inflammatory reaction.
      The development of alternative growth factors may help minimize the adverse
      effects of current osteoinductive therapeutics. Nell-1 (Nel-like molecule-1; Nel
      [a protein strongly expressed in neural tissue encoding epidermal growth factor
      like domain]) is a novel secretory molecule that appears to act more specifically
      on osteoblasts than the BMPs, which can act on multiple cell types. From a
      molecular point of view, Nell-1 is directly regulated by runt-related
      transcription factor 2 (Runx2/Cbfa1), a master regulatory gene controlling bone
      formation. Previous studies showed that Nell-1 accelerates osteogenic
      differentiation in vitro and calvarial bone formation in vivo. We hypothesize
      that Nell-1 may also effectively form bone in spinal fusion. PURPOSE: Our primary
      aim was to assess if direct adenoviral gene delivery with Nell-1 in a
      demineralized bone matrix (DBM) carrier can improve spinal fusion in a rat model.
      Because adenoviral vectors allow for sustained growth factor delivery, they were
      used for initial feasibility testing before protein studies. STUDY
      DESIGN/SETTING: Two groups of 20 athymic rats underwent posterolateral
      intertransverse process spinal fusion at L4-L5 with implanted DBM carrier
      containing either adenovirus coding for Nell-1 (AdNell-1) or control, Lac Z
      (AdLacZ). No cells were implanted. The 20 rats were sacrificed at 6 weeks for
      evaluation of spinal fusion. METHODS: All animals underwent Faxitron radiographs
      at 2, 4, and 6 weeks, manual spine palpation at 6 weeks, and high-resolution
      micro computerized tomography (microCT) at 6 weeks. Spinal fusion rate was
      assessed by: 1) 6-week Faxitron images; 2) manual palpation by three independent
      observers; 3) microCT; and 4) histology. New bone formation was assessed by
      hematoxylin-eosin and Masson trichrome staining on decalcified, coronally
      sectioned spine segments. RESULTS: All differences achieved statistical
      significance. After 6 weeks, direct application of adenoviral Nell-1 in a DBM
      carrier achieved significantly higher rates of spinal fusion over Lac Z controls:
      60% Nell-1 versus 20% Lac Z by manual palpation and 70% Nell-1 versus 20% Lac Z
      by microCT and histology. Histological assessment of bone quality and maturity
      revealed more mature, higher quality bone in all the Nell-1 treated specimens
      relative to Lac Z at 6 weeks. CONCLUSIONS: Spinal fusion is more accurately
      assessed by microCT and histology than manual palpation. Direct application of
      adenoviral Nell-1 in a DBM carrier achieved significantly higher rates of spinal
      fusion over Lac Z controls at 6 weeks. Direct application of adenoviral Nell-1 in
      a DBM carrier also achieved significantly higher rates of spinal fusion over
      other reports in the literature using direct adenoviral BMP application. Direct
      application of adenoviral BMP in an allograft carrier achieved 8% fusion for BMP
      2 and 16% fusion for BMP-7 at 8 weeks. These results indicate that Nell-1 may be
      a potent osteoinductive molecule. In addition, the regulation of Nell-1 by the
      master bone regulatory gene, Runx2 suggests that Nell-1 may exert its effects
      more specifically in osteoblastic cells than BMPs which affect multiple cell
      types. Overall, Nell-1 may fulfil a current need for an osteoinductive factor.

PMID- 17197334
TI  - Posterolateral intertransverse lumbar fusion in a mouse model: surgical anatomy
      and operative technique.
AB  - BACKGROUND CONTEXT: Animal models are frequently used for studying the effect of
      bone graft substitutes or allogeneic materials on osterolateral lumbar fusion.
      Transgenic technology in the mouse provides a unique opportunity to further
      understand the biology of spine fusion. PURPOSE: To describe pertinent lumbar
      spine anatomy and formulate a surgical protocol for posterolateral fusion in the
      mouse model. STUDY DESIGN: Diagnostic model: development of an animal model for
      biologic evaluation of posterolateral spine fusion. METHOD: Ten mice were killed
      to study relevant lumbar spine anatomy and develop a protocol for lumbar spine
      fusion. The L4-L6 fusion protocol was validated in 46 mice for ease of exposure,
      preparation of the posterolateral fusion bed, introduction of bone inductive
      agents, and perioperative care. RESULTS: Anatomy and surgical technique for
      posterolateral intertransverse lumbar fusion in the mouse model are described. A
      paraspinal approach allows exposure of the transverse processes, decortication,
      and graft placement at the L4-L6 intertransverse fusion site. Decortication alone
      did not result in fusion, whereas the use of bone graft resulted in satisfactory
      fusion rates. Perioperative morbidity and mortality rates were low. CONCLUSION:
      The mouse posterolateral lumbar spine fusion model is reproducible, inexpensive,
      and has low complication rates. Knowledge of the relevant anatomy and adherence
      to a well-defined surgical protocol provides a reliable and reproducible
      experimental spine fusion model.

PMID- 17197335
TI  - In vitro measurement of pressure differences using manometry at various injection
      speeds during discography.
AB  - BACKGROUND CONTEXT: Lumbar discography has been widely used to evaluate
      discogenic low back pain. Anecdotal evidence suggests that pain reproduction
      during discography is more closely correlated with peak dynamic pressure than
      with static postinjection pressure. Although there can be a significant
      difference between dynamic and static pressures, to date most discographic
      evaluations use static pressure recorded postinjection (which is stable and
      easily measured). The use of readings taken after injection, rather than readings
      of maximum dynamic peak pressure recorded during injection, appear to increase
      false positives in lumbar discography. High-speed intradiscal injections also
      appear to have potentially confounding effects that may increase the rate of
      false-positive responses during lumbar discography. To date there has been no
      study for the evaluation of peak dynamic intradiscal pressures or for
      differentiating dynamic from static pressures in the nucleus pulposus (NP) in
      response to various speeds of intradiscal injection. PURPOSE: The goal of this
      study was to obtain additional data on potential confounding factors that could
      affect discographic results by assessment of pressures within the NP during
      discography at various injection speeds. The purpose of data collection was to
      more precisely evaluate pressure differences between dynamic and static pressure
      within the NP, evident during discography. STUDY DESIGN: In vitro laboratory
      study. SAMPLES: A total of 82 trials were performed on intervening discs of 82
      porcine cadaver lumbar spines. METHODS: Dynamic and static intradiscal pressures
      were measured with manometry, using two pressure sensors simultaneously during
      intradiscal injection of contrast media at various speeds. The tip of a 25-gauge
      needle was placed in the center of the NP and connected with a pressure
      manometer, which recorded the pressure and therefore the speed of injection. A
      second pressure reading was obtained using a sensor tip connected to a
      transducer; the sensor tip was located separately in the same NP tissue. The
      needle and transducer locations were confirmed by fluoroscopy. OUTCOME MEASURES:
      At low controlled injection speeds (below 0.08 mL/s), the mean peak pressure
      difference in the NP was 4.06 (+/-1.52) psi. With high-speed injections of 0.08
      mL/s or greater, the mean increased abruptly up to 14.52 (+/-4.11) psi (p<.05).
      The data indicate that injections applied slowly resulted in smaller differences
      in pressure within the NP, registered by both manometry and the needle sensor
      tip. Additional samples were taken using both devices to confirm this threshold
      level. RESULTS: With low injection speeds, especially those below 0.08 mL/s,
      differences between dynamic and static pressures on both pressure sensors were
      minor. These differences increased as injection speed became faster. However, at
      fast injection speeds of 0.08 mL/s and above, those differences were
      significantly higher. CONCLUSION: Dynamic and static intradiscal pressures are of
      similar value when measured by manometer and by needle sensor at slow injection
      speeds during discography. However, the pressure differences appeared to rapidly
      increase in response to incremental increases in injection speed. The data from
      these 82 samples suggest that uncontrolled high speeds of intradiscal injections
      are a potential confounding factor, which may increase false-positive responses
      during lumbar discography.

PMID- 17197336
TI  - Disc space injection with marcaine as a method to evaluate painful nonunion of an
      interbody fusion device: a case report.
AB  - BACKGROUND CONTEXT: Discography has been successfully used to distinguish painful
      from asymptomatic intervertebral discs. PURPOSE: To report a case of chronic back
      pain following two-level interbody and posterolateral fusion in the lumbar spine
      that was evaluated with marcaine injection into the disc space. STUDY DESIGN:
      Case report. METHODS: A patient with chronic back pain after a two-level
      anteroposterior lumbar fusion was evaluated. A complete description of the
      history, physical examination, and relevant radiographic images along with a
      brief review of the pertinent literature are included. RESULTS: Injection of
      marcaine into the area of previous interbody fusion resolved the painful
      symptoms, and surgery confirmed the nonunion. CONCLUSIONS: In cases of interbody
      lumbar fusion with questionable solidity, marcain injection within the disc space
      can help in the assessment of the source of pain even at the intervertebral
      spaces with cages.

PMID- 17197338
TI  - Intraoperative somatosensory evoked potential monitoring during anterior cervical
      discectomy and fusion in nonmyelopathic patients--a review of 1,039 cases.
AB  - BACKGROUND CONTEXT: Intraoperative somatosensory evoked potential (SSEP)
      monitoring has been shown to reduce the incidence of new postoperative
      neurological deficits in scoliosis surgery. However, its usefulness during
      cervical spine surgery remains a subject of debate. PURPOSE: To determine the
      utility of intraoperative SSEP monitoring in a specific patient population (those
      with cervical radiculopathy in the absence of myelopathy) who underwent anterior
      cervical discectomy and fusion (ACDF) surgery. STUDY DESIGN: Retrospective
      review. PATIENT SAMPLE: A total of 1,039 nonmyelopathic patients who underwent
      single or multilevel ACDF surgery. The control group (462 patients) did not have
      intraoperative SSEP monitoring, whereas the monitored group (577 patients) had
      continuous intraoperative SSEP monitoring performed. OUTCOME MEASURE: A new
      postoperative neurological deficit. METHODS: SSEP tracings were reviewed for all
      577 patients in the monitored group and all significant signal changes were
      noted. Medical records were reviewed for all 1,039 patients to determine if any
      new neurological deficits developed in the immediate postoperative period.
      RESULTS: None of the patients in the control group had any new postoperative
      neurological deficits. In the monitored group there were six instances of
      transient SSEP changes (1 due to suspected carotid artery compression; 5 thought
      to be due to transient hypotension) which resolved with the appropriate
      intraoperative intervention (repositioning of retractors; raising the arterial
      blood pressure). Upon waking up from anesthesia, one patient in the monitored
      group had a new neurological deficit (partial central cord syndrome) despite
      normal intraoperative SSEP signals. CONCLUSIONS: ACDF appears to be a safe
      surgical procedure with a low incidence of iatrogenic neurological injury.
      Transient SSEP signal changes, which improved with intraoperative interventions,
      were not associated with new postoperative neurological deficits. An
      intraoperative neurological deficit is possible despite normal SSEP signals.

PMID- 17197337
TI  - Incidence of simultaneous epidural and vascular injection during lumbosacral
      transforaminal epidural injections.
AB  - BACKGROUND CONTEXT: The incidence of vascular penetration during contrast
      confirmed fluoroscopically guided transforaminal lumbosacral epidural injections
      has been reported as 8.9% to 21.3% depending on the level of injection. Recently,
      intermittent fluoroscopy was shown to miss more than half of the vascular
      injections observed under live fluoroscopy. The number of misses increased when
      epidural and vascular contrast flow appeared simultaneously, even if the
      fluoroscopic image was taken during contrast injection. To date, no studies have
      documented the incidence of simultaneous epidural and vascular contrast
      injections. Also, most previous studies of vascular injections did not document
      use of live fluoroscopy during contrast injection, so the incidence of vascular
      injections may be higher than reported. PURPOSE: To determine the incidence of
      simultaneous epidural and vascular contrast injection during lumbosacral
      transforaminal epidural injections. STUDY DESIGN/SETTING: A prospective,
      observational, in vivo, study. PATIENT SAMPLE: Patients receiving lumbar
      transforaminal epidural injections at a university-based outpatient spine center.
      OUTCOME MEASURES: Incidence of epidural, vascular, and simultaneous epidural and
      vascular contrast patterns. METHODS: One interventional spine physician and three
      fellows under his direct supervision recorded contrast patterns observed during
      191 fluoroscopically guided lumbosacral transforaminal epidural steroid
      injections with injection of contrast observed under live fluoroscopy. RESULTS:
      The incidence of simultaneous epidural and vascular injection during lumbosacral
      transforaminal epidural injections was 8.9%. The incidence of a vascular
      injection alone was 4.2%, for a total vascular injection incidence of 13.1%.
      Subjects with a simultaneous epidural and vascular injection who returned for
      repeat injection had a statistically significant chance of a repeat simultaneous
      epidural and vascular injection when the injection was done at the same location.
      Fluoroscopy time was significantly increased, an average of 8.8 seconds, when a
      vascular injection was identified. There was no statistically significant
      correlation between the incidence of simultaneous epidural and vascular injection
      with subjects' age, sex, level of injection, side of injection, needle gauge, or
      diagnosis. CONCLUSIONS: Simultaneous epidural and vascular injection is twice as
      likely to occur as vascular injection alone. Use of intermittent fluoroscopy can
      miss the transient appearance of the vascular component of these injections,
      giving the false impression of successful contrast placement. In light of these
      results, live fluoroscopy is recommended during contrast injection for
      confirmation of lumbosacral transforaminal epidural injections.

PMID- 17197339
TI  - The results of nucleoplasty in patients with lumbar herniated disc: a prospective
      clinical study of 52 consecutive patients.
AB  - BACKGROUND CONTEXT: Nucleoplasty is a minimally invasive, percutaneous procedure
      that uses radiofrequency energy to ablate nuclear material and create small
      channels within the disc. PURPOSE: To evaluate the efficacy of nucleoplasty
      technique in patients with leg pain caused by radicular encroachment. STUDY
      DESIGN/SETTING: A prospective clinical study of subjects with lumbar disc
      herniation, and radicular pain resistant to previous medical treatment and
      physiotherapy for a period of at least 3 months. PATIENT SAMPLE: Fifty-two
      consecutive patients with leg pain and magnetic resonance imaging evidence of
      small and medium-sized herniated discs correlating with the patient's symptoms
      (contained disc herniation<6 mm, with a disc height>/=50% in comparison to normal
      adjacent discs) were included. OUTCOME MEASURES: Visual analogue scale (VAS) was
      administered and Oswestry disability questionnaires were filled out at
      preprocedure and postprocedure 2 weeks, 6 months, and 1 year. Reduction of
      analgesic treatment and the patients' satisfaction were also recorded. METHODS:
      All procedures were performed under local anesthesia and fluoroscopic guidance on
      an outpatient basis. Patients underwent discography to evaluate annular integrity
      just before nucleoplasty. Channels were created in the nucleus by advancing the
      radiofrequency probe (ablating) and withdrawing it (coagulation). In all patients
      six channels were created. RESULTS: Thirty-four patients had one and 18 had two
      discs treated; a total of 70 procedures were performed. Mean age of patients was
      44.8+/-8.6 years. The mean follow-up period was 12.1+/-1.6 months. Mean VAS
      reduced from preprocedure 7.5 to 3.1 at postprocedure 6 months and to 2.1 at the
      latest follow-up. Mean Oswestry index decreased from 42.2 to 24.8 at 6 months and
      to 20.5 at the latest examination. Analgesic consumption was stopped or reduced
      in 42 patients (85%) at 6 months and in 46 patients (94%) 1 year after the
      procedure. Overall patient satisfaction was 81% at 2 weeks, 85% at 6 months, and
      88% at the latest follow-up. There were no complications related to the
      procedures. CONCLUSIONS: Our results encourage us to use nucleoplasty in
      carefully selected patients with leg pain caused by radicular encroachment. We
      recommend applying this minimally invasive technique only in those patients with
      small (<6 mm) contained disc herniations, with a disc height of>or=50% and with
      annular integrity.

PMID- 17197341
TI  - Tophaceous gout of the lumbar spine mimicking pyogenic discitis.
AB  - BACKGROUND CONTEXT: Gout of the spine is very rare. Forty-one cases of gout
      affecting the spine have been reported. PURPOSE: To present a patient with
      tophaceous gout of the lumbar spine mimicking pyogenic discitis. STUDY DESIGN:
      Case report. METHODS: The medical record, including operative notes, progress
      notes, discharge summary, clinical notes, radiological study, and pathological
      studies was reviewed. RESULTS: The patient had acute low back pain and
      radiculopathy with high spiking fever. Therefore, pyogenic discitis was
      suspected. However, histological diagnosis revealed tophaceous gout. CONCLUSIONS:
      Tophaceous gout of the spine is very rare. However, when a patient presents with
      acute back pain and fever, spinal gout should be considered, particularly in a
      patient with a previous history of hyperuricemia or gout.

PMID- 17197342
TI  - Treatment of symptomatic spondyloptosis in an adult previously treated with in
      situ fusion and instrumentation by L5 vertebrectomy and L4-S1 instrumented
      reduction.
AB  - BACKGROUND CONTEXT: One traditional treatment for spondylolisthesis is fusion.
      However, for high-grade spondylolisthesis and spondyloptosis, posterior fusion
      has had high rates of nonunion, progression, and persistent physical deformity.
      Thus, some surgeons have recommended reduction and instrumentation. One such
      technique (Gaines procedure) entails a two-stage procedure: L5 vertebrectomy
      anteriorly, followed by resection of the L5 posterior elements and instrumented
      reduction of L4 onto S1. However, to our knowledge, there is no report of
      reversing the fusion and deformity reduction in a symptomatic patient with
      previous solid fusion of the spondyloptosis at L5-S1. PURPOSE: To present the
      first reported revision via the Gaines procedure for failed fusion secondary to
      spondyloptosis. STUDY DESIGN: Patient report. METHODS: A 24-year-old woman, who
      had undergone multiple procedures for L5-S1 spondylolisthesis and a final fusion
      and instrumentation attempt, presented with continued urinary retention, leg and
      back pain, and inability to stand. She subsequently underwent posterior hardware
      removal, followed by anterior L5 vertebral body resection. In the second stage,
      she had posterior osteotomy of the previous L5-S1 fusion, resection of the
      posterior elements of L5, and reduction and instrumentation of L4 to S1. RESULTS:
      At the 2-year follow-up, she had full resolution of symptoms, full return of
      motor strength, and resolution of urinary retention. CONCLUSIONS: The Gaines
      procedure has been performed successfully in patients without previous fusions at
      the level of spondylolisthesis or spondyloptosis. Patients for whom the
      traditional posterior fusion fails still may be candidates for this procedure,
      albeit at increased risk of neurologic injury.

PMID- 17197343
TI  - Lumbar intraradicular disc herniation: report of a rare and preoperatively
      unpredictable case and review of the literature.
AB  - BACKGROUND CONTEXT: Intraradicular lumbar disc herniation is rare, having been
      reported to date in only three postoperative patients. The diagnosis is typically
      made intraoperatively. PURPOSE: To report a fourth case of intraradicular disc
      herniation, to emphasize its radiological characteristics and operative findings.
      STUDY DESIGN: Case report. PATIENT SAMPLE: A 41-year-old female. METHODS:
      Retrospective case review. RESULTS: The patient underwent a second operation and
      intraradicular disc fragment was removed. She was completely well at her 9-month
      check up. CONCLUSIONS: The diagnosis, mechanism, and surgical treatment of
      intraradicular lumbar disc herniation are reviewed. The round shape of the
      sequestrated fragment, as seen on magnetic resonance imaging, may help to
      establish the correct diagnosis.

PMID- 17197344
TI  - Intradural lumbar disc herniation--is it predictable preoperatively? A report of
      two cases.
AB  - BACKGROUND CONTEXT: Intradural disc herniations are thought to be rare events,
      and there have been relatively few literature reports of intradural disc
      herniations available with regard to magnetic resonance imaging findings.
      PURPOSE: The authors describe two patients with intradural lumbar disc
      herniations, one with and one without preoperative diagnosis, who had different
      postoperative outcomes. STUDY DESIGN: Case study METHODS: The first patient
      underwent an extended L3 subtotal laminectomy followed by bilateral medial
      facetectomy and foraminotomy at L3-L4. A durotomy uncovered large disc fragments
      comprised of friable disc materials and end plates, after no clear disc
      herniation was found in the epidural space. The second patient underwent anterior
      lumbar interbody fusion after a preoperative diagnosis of intradural disc
      herniation. RESULTS: The first patient experienced a marked reduction of pain and
      progressive recovery of sensory disturbance, but neurologic examination showed
      right foot drop postoperatively. Two years after surgery, she can not walk
      without a cane because the neurologic deficit of the right ankle has shown no
      improvement. Two days after surgery, the second patient was allowed to ambulate
      with a lumbar orthosis. Neurologic examination showed no motor deficit. Twenty
      one months after surgery, the patient reports minimal back pain when sitting on a
      chair for prolonged periods of time. CONCLUSION: Our cases highlight the
      importance of preoperative diagnosis in the treatment of intradural lumbar disc
      herniations. The potential presence of an intradural disc herniation must always
      be considered preoperatively on a patient whose magnetic resonance imaging study
      demonstrates the "hawk-beak sign" on axial imaging as well as abrupt loss of
      continuity of the posterior longitudinal ligament (PLL). This association results
      in an adequate surgical approach, thereby reducing the chance of postoperative
      neurologic deficit. Finally, anterior lumbar interbody fusion can be a reasonable
      alternative in the treatment of intradural lumbar disc herniations.

PMID- 17197345
TI  - The Lumbar Spine Outcomes Questionnaire: its development and psychometric
      properties.
AB  - BACKGROUND CONTENT: There are currently a number of generic and disease-specific
      instruments for assessing complaints of low back pain (LBP). None provide the
      comprehensive coverage of the wide range of factors that are considered essential
      in evaluating treatment outcomes. PURPOSE: To develop and evaluate the
      psychometric properties of a comprehensive, disease-specific questionnaire for
      characterizing complaints of LBP and evaluating the outcomes of treatments for
      these complaints. STUDY DESIGN: A clinical-cohort study of a large, convenience
      sample of LBP patients. METHODS: We have developed a comprehensive, disease
      specific questionnaire for characterizing complaints of LBP and evaluating the
      outcomes of treatments for these complaints. A large group of patients who sought
      treatment for LBP (n=2539) completed the Lumbar Spine Outcomes Questionnaire
      (LSOQ) before treatment, and at 12 and 24 months after treatment. For each
      subject and for each evaluation period, scores on six composite measures were
      derived from the subjects' responses to the questionnaire: a LBP severity score,
      a leg pain severity score, a functional disability score, a psychological
      distress score, a physical symptoms score, and a health-care utilization score.
      These scores were used to evaluate the reliability, validity, and responsiveness
      of the questionnaire. RESULTS: Test-retest reliability of the LSOQ was evaluated
      by correlating the subject's 12-month scores on each composite measure with the
      corresponding 24-month scores. Intraclass coefficients of correlation were used.
      The obtained coefficients of correlation [(a) LBP severity, 0.87; (b) leg pain
      severity, 0.85; (c) functional disability, 0.87; (d) psychological distress,
      0.88; (e) physical symptoms other than pain, 0.82; and (f) health-care
      utilization, 0.76] indicate good test-retest reliability for the LSOQ. Construct
      validity was evaluated by correlating scores on the composite measures derived
      from the LSOQ with scores on measures of the same constructs derived from the
      Oswestry Low Back Pain Disability Questionnaire and the Short Form 36-Item Health
      Survey. The coefficients of correlation were relatively high (mostly between .7
      and .9), indicating good construct validity. Construct validity was also
      evaluated by comparing the scores of groups of subjects who were known to differ
      or not to differ on the composite measures, using multivariate analyses of
      variance. Significant multivariate and univariate differences were obtained
      between groups who were expected to differ (ie, surgically and nonsurgically
      treated patients). No significant differences were found for groups who were not
      expected to differ (ie, patients with similar diagnosis, but different surgical
      treatments). Responsiveness was assessed by evaluating differences in the 24
      month change scores between improved and unimproved subjects. Large and
      significant differences were obtained between improved and unimproved subjects
      for all composite measures derived from the LSOQ. The observed effect sizes
      ranged from .68 to 1.17 indicating that the LSOQ is highly responsive.
      CONCLUSION: The LSOQ appears to be acceptable to patients, easy to administer,
      highly reliable, valid, and responsive. It provides information on demographics,
      pain severity, functional disability, psychological distress, physical symptoms,
      health-care utilization, and satisfaction. It should be considered for use in
      both clinical and research applications as well as regulatory review involving
      patients with LBP complaints.

PMID- 17197346
TI  - Regarding; Bryan disc related cervical kyphosis.

PMID- 17197347
TI  - In vitro maturation of human oocytes.
AB  - Immature oocyte retrieval followed by in vitro maturation (IVM) opens a new
      horizon for modern assisted reproductive technologies (ART). Recent studies in
      IVM make it a feasible alternative to in vitro fertilization. Antral follicle
      count is correlated with the pregnancy rate, so women with polycystic ovarian
      syndrome or polycystic ovaries are the best candidates for IVM. IVM can also be
      offered to women at risk of ovarian hyperstimulation syndrome or poor responders.
      From the available information, IVM is a safe procedure and does not increase
      congenital anomalies or pregnancy complications. Further research is necessary in
      order to apply this technique to other patients.

PMID- 17197348
TI  - Differential expression of growth-, angiogenesis- and invasion-related factors in
      the development of placenta accreta.
AB  - Placenta accreta is the major cause of maternal death complicated by massive
      peripartum hemorrhage. Its development is traditionally considered to be related
      to a decidual defect caused by previous cesarean deliveries or uterine
      curettages. Usually, placental villi firmly adhere to the superficial myometrium
      and deeply invade, or even penetrate, the uterine wall. Abnormal uteroplacental
      neovascularization is another characteristic. Therefore, we hypothesized that
      placenta accreta develops as a result of abnormal expressions of growth-,
      angiogenesis- and invasion-related factors in trophoblast populations. We have
      found, in pregnancies complicated by placenta accreta: upregulated epidermal
      growth factor receptor and downregulated c-erbB-2 oncoprotein in
      syncytiotrophoblasts; downregulated vasculoendothelial growth factor receptor-2
      expression in syncytiotrophoblasts and increased vasculoendothelial growth factor
      in placental lysates; and downregulated Tie-2 expression in syncytiotrophoblasts
      and enhanced angiopoietin-2 level in placental lysates. However, matrix
      metalloproteinase expression was not upregulated, so the association of these
      invasion-related molecules with placenta accreta is less likely. Taken together,
      these findings imply that complex factors, either alone or in combination, might
      be responsible for the development of placenta accreta. Further studies are
      needed to understand the signaling pathways and possible genetic events.

PMID- 17197349
TI  - Nm23-H1: a metastasis-associated gene.
AB  - The protein product of nm23-H1 gene has activity of nucleoside diphosphate (NDP)
      kinase, which catalyzes the phosphorylation of nucleoside diphosphates to the
      corresponding nucleoside triphosphates. Reductions in nm23 expression have been
      significantly associated with aggressive behavior in melanoma, breast, colon, and
      gastric carcinomas. On the contrary, high levels of nm23 gene expression are
      noted in the advanced stage of thyroid carcinomas and associated with significant
      reductions in survival for neuroblastoma and osteosarcoma patients. Although
      expression of nm23/NDP kinase is divergent in various malignant tumors, its
      reduced expression seems to be related to increased metastatic potential in most
      carcinoma types. However, it is hypothesized that nm23 may play a tissue-specific
      role, and that different regulatory mechanisms may act in different tumors. In
      ovarian carcinoma, nm23-H1/NDP kinase may be correlated with some
      clinicopathologic characteristics. In cervical cancer, nm23-H1 is probably
      involved in cervical carcinogenesis and correlated with some aggressive
      parameters. Overexpression of nm23-H1 protein may indicate poor survival for
      cervical cancer patients. Other than histidine 118 residue (amino acid sequence
      118: histidine) concerned with NDP kinase activity of nm23-H1, serine 120 (amino
      acid sequence 120: serine) related activity of histidine-dependent protein
      phosphotransfer was recently reported to be responsible for its biological
      suppressive effects. To inhibit metastatic potential, nm23-H1 is also
      demonstrated to co-immunoprecipitate the kinase suppressor of Ras and
      phosphorylate it, and therefore reduce activation of the extracellular signal
      regulated kinase mitogen-activated protein kinase pathway in response to
      signaling.

PMID- 17197350
TI  - Pathogens in maternal blood and fetal cord blood using Q-PCR assay.
AB  - OBJECTIVE: To evaluate the rates of infection of asymptomatic fetuses and mothers
      through fetal cord blood and maternal blood examination results. MATERIALS AND
      METHODS: Quantitative PCR (Q-PCR) was used to detect pathogens in maternal
      peripheral blood and fetal cord blood after delivery of term pregnancy at
      Buddhist Tzu Chi Medical Center, Hualien, between July 2002 and June 2003.
      RESULTS: We used Q-PCR to detect pathogens in 29 samples of maternal blood. The
      maternal hepatitis B virus (HBV) DNA detection rate was 51.72% (15/29); for human
      cytomegalovirus DNA, the detection rate was 10.34% (3/29) and for Chlamydia
      trachomatis DNA the detection rate was 3.45% (1/29). No Neisseria gonorrhoeae DNA
      was detected. Whereas, in 29 samples of paired fetal cord blood, the detection
      rates were 27.59% (8/29), 10.34% (3/29), and 3.45% (1/29) for HBV DNA, C.
      trachomatis DNA, and N. gonorrhoeae DNA, respectively. No human cytomegalovirus
      DNA was detected in fetal cord blood. CONCLUSION: Our results revealed an
      unexpectedly high incidence of pathogens in fetal cord blood. Screening for the
      above pathogens in donor cord blood in cord blood banks using Q-PCR is strongly
      urged to decrease morbidity and mortality rates in fetal cord blood stem cell
      transplant recipients.

PMID- 17197351
TI  - Outcome of pregnancy in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To study the maternal and fetal outcomes in women with systemic lupus
      erythematosus (SLE). MATERIALS AND METHODS: Over a period of 10 years, 24
      pregnancies in 17 females with SLE in a single center were enrolled. Fetal and
      maternal outcomes were studied retrospectively. RESULTS: The mean patient age was
      27.7 years. Twenty-one of the 24 pregnancies occurred in the period of disease
      remission at the time of conception. Proteinuria presented in 12 pregnancies;
      however, no patient developed acute renal failure or deterioration of renal
      function. There were three cases of preeclampsia in this study. Two patients had
      their disease flare up and delivered stillborns. One woman with secondary
      antiphospholipid syndrome (APS) had a fetal loss. There was no maternal
      mortality. The mean gestation age was 34.3 weeks (range, 17-41 weeks), and the
      mean birth weight was 2,179 g. The mean APGAR scores were 8 and 9 at 1 and 5
      minutes, respectively. One baby with congenital atrioventricular block was born
      to a mother with positive anti-SSA antibody. There were five cases (20.8%) of
      intrauterine growth retardation and 10 preterm deliveries (41.6%) in this study.
      CONCLUSION: Pregnancy is relatively safe in women with SLE in remission but
      should be considered as a high-risk pregnancy. APS is associated with poor
      pregnancy outcome. The patient needs to cooperate with obstetricians and
      physicians for optimal disease control and detailed monitoring throughout the
      gestation.

PMID- 17197352
TI  - Ultrasonographic evaluation of the change in uterine fibroids induced by
      treatment with a GnRH analog.
AB  - OBJECTIVE: To investigate the change in volume of uterine fibroids after GnRH
      analog (GnRHa) treatment. MATERIALS AND METHODS: Twenty-five patients who had a
      uterine leiomyoma were included in this study. Four of them were lost to follow
      up during the study, and a myomectomy was performed on the remaining subjects.
      All of these patients received two doses, 4 weeks apart, each of 3.75 mg
      leuprorelin acetate subcutaneously (Leuplin depot, a GnRHa) before the operation.
      The vascularization index (VI), flow index (FI), vascularization-flow index
      (VFI), pulsative index (PI), resistance index (RI), vascular patterns
      (histogram), blood flows, and sizes (volume and largest diameter) of each fibroid
      were measured with power Doppler by the same technician every month before the
      operation. In addition, the total blood loss and time required for each operation
      were also recorded. RESULTS: Results of this study showed that the volume of the
      uterus and the fibroids, but not the vascularity, including VI, FI, VFI, PI and
      RI, decreased significantly after two doses of GnRHa treatment. In addition,
      blood loss during the operation decreased significantly compared to an untreated
      group. CONCLUSION: We found that the volumes of the uterus and fibroids decreased
      significantly after treatment with two consecutive doses (given a month apart) of
      GnRHa. The 3D color Doppler including a histogram and blood flow parameters is
      another useful tool for fibroid evaluation.

PMID- 17197353
TI  - Changes of urethral pressure profilometry in pubovaginal sling and modified Burch
      colposuspension procedures.
AB  - OBJECTIVE: To evaluate the different effects on urethral pressure profilometry
      (UPP) in pubovaginal slingplasty (PVS) and modified Burch colposuspension (MBC)
      procedures. MATERIALS AND METHODS: This was a descriptive study of urodynamic
      parameters and urethral pressure profilometry. A total of 63 patients with
      successful anti-incontinence surgery were recruited for this study. Thirty-eight
      women had received MBC before 1998, to stabilize the bladder neck and the
      anterior vaginal wall. Twenty-five women had undergone autologous PVS to elevate
      the backstop effect on the proximal urethra between 1998 and 2000. All patients
      were followed-up for at least 24 months after surgery. RESULTS: The mean age of
      patients in the PVS group was 52.5 years (range, 32-70 years), and 45.5 years
      (range, 31-61 years) in the MBC group. Age and parity were not significantly
      different between the two groups. The pressure transmission ratio (PTR) of the
      urethra increased significantly in both groups during the postoperative
      evaluation. Patients who had the MBC procedure showed an increased PTR at quarter
      (Q) Q1, Q2, and Q3 of the urethra. However, in the PVS group, the PTR increased
      only at Q3. The urethral closure pressure elevated significantly after MBC, but
      there were no significant changes after PVS. CONCLUSION: Our results indicate
      that different effects on UPP are evident in the PVS and MBC procedures. These
      two procedures should be considered in different anti-incontinence effect.

PMID- 17197354
TI  - Fetal intracranial hemorrhage (fetal stroke): report of four antenatally
      diagnosed cases and review of the literature.
AB  - OBJECTIVE: Neonatal intracranial hemorrhage (ICH) has been estimated to be high
      in premature infants, occurring in approximately 40% of infants of less than 32
      weeks' gestation. However, the true incidence of ICH in utero has not been
      determined. We present our experience with four cases of fetal ICH (fetal
      stroke), which was detected prenatally by ultrasonography (US). MATERIALS AND
      METHODS: Four cases of fetal ICH were identified over a 2-year period at the
      prenatal unit of Taichung Veterans General Hospital, Taiwan. Prenatal and
      neonatal sonograms, computed tomography (CT) scan or magnetic resonance imaging
      (MRI), medical records, and the clinical course were assessed retrospectively. In
      each case, a series of initial and follow-up obstetric sonograms were available.
      Fetal stroke was recognized by several sonographic features: irregular echogenic
      brain mass, intraventricular echogenic foci or periventricular echodensities;
      ventriculomegaly; and posthemorrhagic hydrocephalus (PHH). A detailed
      investigation for possible etiology of fetal ICH was performed in all cases.
      RESULTS: Transabdominal US showed hyperechoic lesions in the lateral ventricle
      and ventriculomegaly in three of the four fetuses, and a massive intraparenchymal
      hemorrhage in the remaining one. Three fetuses were born vaginally and one by
      cesarean section due to an enlarged head circumference. Abnormal nonstress tests
      and abnormal flow velocity waveforms in the umbilical and middle cerebral
      arteries were present in two cases. Intrapartum fetal death and neonatal death
      occurred in the first two cases associated with maternal preeclampsia at 31 and
      27 weeks, respectively. In the remaining two infants, the one in case 3 underwent
      ventriculoperitoneal shunting, which developed normally at the age of 18 months.
      The other infant in case 4 had PHH after suspicious choroids plexus hemorrhage,
      and the detailed information regarding the cause of neonatal death was not
      available. CONCLUSION: This small series demonstrate that an antenatal diagnosis
      of fetal stroke with intraventricular hemorrhage Grades III and IV or with brain
      parenchymal involvement appears to be associated with poor neurologic outcome.
      Due to the significant neonatal neurologic impairment and potential medicolegal
      implications of antepartum fetal ICH, it follows that obstetricians and
      sonographers should be familiar with predisposing factors and typical diagnostic
      imaging findings of rare in utero ICH events.

PMID- 17197355
TI  - Failure of laparoscopy to relieve ureteral obstruction secondary to
      endometriosis.
AB  - OBJECTIVES: To present a case of hydronephrosis and hydroureter secondary to
      pelvic endometriosis and to discuss the pitfalls in laparoscopic management. CASE
      REPORT: A 37-year-old nulligravida woman had mild elevation of blood pressure for
      about 1 year without abdominal pain, dyspareunia, or dysmenorrhea. Renal
      ultrasound revealed left hydronephrosis and a 4-cm pelvic cyst. Intravenous
      pyelogram showed distal ureteral obstruction. An MRI with fat saturation
      disclosed a left ovarian endometrioma and a lesion in the uterosacral ligament
      causing periureteral compression. Laparoscopic findings included a dilated left
      ureter above the uterosacral ligament, left uterosacral ligament endometriosis
      with adhesions, and a 4-cm left ovarian endometrioma. Cystoureteroscopy showed
      external ureteral compression 2 cm above the ureteral orifice. A ureteral
      catheter was placed. The left endometrioma was enucleated and ureterolysis was
      performed. The latter procedure had to be discontinued because of bleeding from
      descending uterine vessels. The ureteral catheter was removed 2 months later and
      her blood pressure gradually returned to normal. However, after 1 year, she was
      found to have recurrent hydronephrosis and underwent segmental resection of the
      distal ureter and reconstruction by end-to-end reanastomosis. CONCLUSION: In
      women of reproductive age, hydronephrosis and hypertension may be the only
      symptoms of endometriosis. While laparoscopic treatment is useful in
      endometriosis, it may fail in the presence of chronic inflammation and severe
      fibrosis.

PMID- 17197356
TI  - Prenatal diagnosis of alobar holoprosencephaly with cystic hygroma.
AB  - OBJECTIVE: Holoprosencephaly is a kind of brain anomaly characterized by
      inadequate cleavage of the prosencephalon during early embryogenesis. In
      addition, holoprosencephaly associated with cystic hygroma and hydrops fetalis
      has never been reported. In this article, we report a rare case of
      holoprosencephaly associated with cystic hygroma and hydrops fetalis diagnosed
      prenatally. CASE REPORT: A 28-year-old woman, gravida 2, para 0, artificial
      abortion 1, was referred to our antenatal clinic at 16 weeks of gestation due to
      fetal cystic hygroma detected by prenatal routine ultrasonography at a local
      hospital. In our clinic, single ventricle with fused thalami and cystic mass at
      the fetal neck as well as hydrops fetalis were noted by level II ultrasound.
      Under the impression of holoprosencephaly with cystic hygroma and hydrops
      fetalis, termination of pregnancy with misoprostol was undertaken. The
      histopathology of fetal autopsy confirmed our diagnosis and disclosed additional
      intracranial abnormalities. CONCLUSION: Fetus with holoprosencephaly might have
      other associated structural abnormalities. Cystic hygroma and hydrops fetalis are
      rare associations. Meticulous sonographic examination to depict the associated
      defects are necessary in any fetus with holoprosencephaly.

PMID- 17197357
TI  - Experience with conservative strategy of uterine artery embolization in the
      treatment of placenta percreta in the first trimester of pregnancy.
AB  - OBJECTIVE: There is little prospective experience in the conservative treatment
      of placenta percreta during the first trimester in order to preserve uterine
      fertility. We describe herein our experience with uterine artery embolization
      (UAE) in the management of placenta percreta at 9 weeks of gestation. CASE
      REPORT: A 36-year-old woman, gravida 3, para 1, was referred for ultrasonographic
      evaluation because of suspected molar pregnancy due to persistent vaginal
      spotting at 9 weeks of gestation. A Grade 3+ lacunar flow pattern with multiple
      bizarre and large irregular sonolucent spaces were observed. Color Doppler
      imaging revealed extensive turbulent lacunar blood flow perfusing throughout the
      whole surrounding uteroplacental tissues and fetus. The patient was informed of
      the situation and she had a strong desire to avoid surgery. Conservative
      management with bilateral UAE was performed using polyvinyl alcohol particles to
      promote involution and shedding of the abnormally adherent placenta. However, an
      unsatisfactory vessel-occluding effect caused by extensive collateral supply was
      still detected after repeated UAE. We, therefore, performed hysterectomy, and the
      patient had an uneventful postoperative course. CONCLUSION: The efficacy and
      complications of UAE as a therapeutic modality for the conservative management of
      invasive placentation in the first trimester of pregnancy are not clear, as this
      is the first report of its kind. However, although UAE had failed in this case,
      it may still be a useful procedure as a prophylactic measure before surgical
      intervention, and hysterectomy can also be performed for better control of
      operative hemorrhage.

PMID- 17197358
TI  - Presacral epidermoid cyst with right hydronephrosis.
AB  - OBJECTIVE: Epidermoid cyst of the presacral space is a rare congenital lesion of
      ectodermal origin. Presacral epidermoid cyst with hydronephrosis is even rarer
      and has never been reported in Taiwan. Herein, we present a patient with
      presacral epidermoid cyst with right hydronephrosis. CASE REPORT: A 62-year-old
      woman had low abdominal pain for 2 weeks and was referred to our hospital for
      further management. In our hospital, computed tomography revealed a
      multilobulated cystic tumor (20 x 15 x 12 cm) in the lower abdomen, complicated
      with right severe hydronephrosis. Laparotomy was undertaken and a presacral tumor
      was removed. The pathologic diagnosis was an epidermoid cyst. CONCLUSION: A
      presacral epidermoid tumor is a rare tumor and a large presacral cystic tumor may
      mimic an ovarian tumor in imaging. All presacral tumors with or without symptoms
      should be evaluated thoroughly before operation. Complete surgical excision,
      preserving adjacent organs' function, should be kept in mind.

PMID- 17197359
TI  - Submucous myoma induces uterine inversion.
AB  - OBJECTIVE: Inversion of the uterus is indeed a rarity for a gynecologist. The
      puerperal variety is associated with pregnancy, including term pregnancy and
      abortion. The nonpuerperal condition may be tumor-induced or idiopathic. We
      present a nonpuerperal uterine inversion and discuss a reasonable plan for its
      management. CASE REPORT: A 42-year-old, unmarried woman without sexual experience
      and any systemic diseases noted a mass outside of the vaginal introitus combined
      with massive vaginal bleeding and abdominal pain of sudden onset after taking
      laxative agents for colonoscopic preparation. Then she had voiding difficulty
      with distended bladder. A suprapubic urinary catheter was inserted and 800 mL
      urine was drained out. The patient received emergency tumor resection and
      subtotal hysterectomy. The diagnosis of uterine inversion was confirmed during
      operation. The postoperative course was uneventful and she was discharged without
      complication. CONCLUSION: Nonpuerperal inversion of the uterus is rarely
      encountered by gynecologists. Diagnosis of uterine inversion is often not easy
      and imaging studies might be helpful. Surgical treatment is the method of choice
      in nonpuerperal uterine inversion.

PMID- 17197360
TI  - Burkitt'S lymphoma mimicking a primary gynecologic tumor.
AB  - OBJECTIVE: Burkitt's lymphoma (BL) occurs mostly in children; bilateral ovarian
      involvement mimicking a gynecologic malignancy in adults is extremely rare. Here,
      we report a patient with BL mimicking a gynecologic tumor. CASE REPORT: A 50-year
      old Taiwanese woman presented with the complaint of persistent lower abdominal
      distension with dull pain, easy satiety, and progressively increasing abdominal
      girth for 2 weeks. Amenorrhea was also noted for about 2 months, and her review
      of systems was negative for the common "B" symptoms associated with lymphoma. At
      our hospital, imaging studies revealed a huge pelvic mass (10.8 x 8.7 cm),
      suggesting a large subserous myoma or an ovarian tumor. Under the impression of
      pelvic mass, she underwent exploratory laparotomy. Primary ovarian sex-cord
      malignancy with cecum involvement was impressed by the primitive intraoperative
      frozen section report. Subsequently, an optimal cytoreductive operation with
      right hemicolectomy was performed. However, final histopathologic report was an
      extranodal multifocal BL. CONCLUSION: Although extranodal BL in ovaries is a rare
      condition, it should be noted in the differential diagnosis of pelvic gynecologic
      malignancies.

PMID- 17197361
TI  - Mitotically active leiomyoma of the uterus in a postmenopausal breast cancer
      patient receiving tamoxifen.
AB  - OBJECTIVE: Mitotically active leiomyoma of the uterus complicated with
      postmenopausal vaginal bleeding has never been reported in Taiwan. Here, we
      present a case of mitotically active leiomyoma of the uterus complicated with
      postmenopausal vaginal bleeding in a breast cancer patient who had been receiving
      tamoxifen for 2 years. CASE REPORT: A 56-year-old woman visited our clinic due to
      abnormal vaginal spotting for 3 months. This patient had been menopausal for
      about 6 years without hormone replacement therapy. She had been suffering from
      breast cancer, had undergone conservative breast surgery, and had been taking
      tamoxifen (20 mg/day) for 2 years. Pelvic ultrasound was performed and revealed
      an 8.9 x 7.7 cm uterine mass. After simple total hysterectomy, we found an
      enlarged uterus with a mass over the posterior wall. Final pathology demonstrated
      a mitotically active leiomyoma, adenomyosis of the uterus, and proliferation of
      the endometrium. CONCLUSION: Endometrial cancer is rarely noted in breast cancer
      patients taking tamoxifen. Further, none have reported mitotically active
      leiomyoma of the uterus. From this case, endometrial proliferation and
      mitotically active leiomyoma of the uterus may be related to tamoxifen therapy,
      and should not be neglected in breast cancer patients.

PMID- 17197362
TI  - Uterine rupture due to traumatic assisted fundal pressure.
AB  - OBJECTIVE: Uterine rupture is potentially a life-threatening condition for both
      mother and infant. In this article, we report a rare occurrence of uterine
      rupture due to traumatic assisted fundal pressure associated with hydrops fetalis
      and shoulder dystocia. CASE REPORT: A 29-year-old woman was admitted for
      termination of pregnancy at 34 weeks' gestation because of fetal hydrops.
      Assisted uterine fundal pressure was done during delivery because of coexistent
      shoulder dystocia. After a series of assisted uterine fundal pressure, a dead
      hydropic baby weighing 4,000 g was delivered, and persistent postpartum
      hemorrhage occurred. An emergency laparotomy was performed, which revealed a
      large left broad ligament hematoma with multiple bleeding points. The bleeders
      were safely sutured and the tears of the left lateral uterine wall were primarily
      restored. The patient was discharged 8 days later. CONCLUSION: Assisted fundal
      pressure during painful delivery can be traumatic and results in uterine rupture.
      In this article, we suggest that uterine rupture should be considered whenever a
      pregnant woman experiences a sudden onset of abdominal pain during the course of
      assisted uterine fundal pressure.

PMID- 17197363
TI  - Vaginal expulsion of a submucosal myoma during treatment with long-acting
      gonadotropin-releasing hormone agonist.
AB  - OBJECTIVE: Gonadotropin-releasing hormone agonist (GnRH agonist) therapy has been
      useful as an adjunct before myomectomy or hysterectomy for uterine myoma. CASE
      REPORT: A 26-year-old woman without sexual exposure was diagnosed with a
      submucosal myoma and treated with long-acting GnRH agonist. This patient
      exhibited heavy menstruation and severe anemia for 2 years and consulted our
      outpatient department. Transabdominal ultrasound demonstrated a 3.5-cm submucosal
      myoma within the endometrial cavity. The patient showed a marked suppression of
      serum estradiol concentrations throughout the treatment (< 20 pg/mL at the second
      dose injection). The volume of the uterus and uterine myoma decreased to two
      thirds of the original size at the end of the second dose injection. However, a
      sudden onset of severe abdominal cramping pain occurred on the 76th day and a
      ping-pong sized mass was expelled from the vagina. She visited our outpatient
      department for evaluation, where ultrasound failed to detect the previous
      submucosal uterine myoma. A 3-year follow-up has been uneventful. CONCLUSION:
      Spontaneous expulsion of submucosal myomas might occur after the administration
      of GnRH agonist; hence, it may be an acceptable alternative for symptomatic
      females without sexual exposure.

PMID- 17197364
TI  - Menstrual abnormalities in a woman with ACTH-dependent pituitary macroadenoma
      mimicking polycystic ovary syndrome.
AB  - OBJECTIVE: Here, we present a case of ACTH-dependent pituitary macroadenoma
      (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary
      syndrome (PCOS). CASE REPORT: A 20-year-old nulligravid woman had been suffering
      from oligomenorrhea, amenorrhea, and moderate hirsutism since the age of 18
      years. She visited a gynecologic clinic where PCOS was impressed according to the
      clinical manifestation and ultrasound finding. The patient responded to
      medication in the 1st year, but gradually failed to induce menses. She was
      advised to visit the endocrinology department for secondary amenorrhea and
      endocrine survey. Physical examination revealed central obesity, supraclavicle
      fatpad, abdominal striae, and myopathy of four limbs. Endocrine studies revealed:
      serum prolactin 21 ng/mL (3.0-20 ng/mL), FSH 5.69 mIU/mL (3.4-10.0 mIU/mL), LH
      1.01 mIU/mL (1.1-11.6 mIU/mL), E2 < 20 pg/mL (follicular phase 53-258 pg/mL),
      ACTH 110 pg/mL (0-46.0 pg/mL), cortisol 26.7 microg/dL at 8 a.m. (5.0-25
      microg/dL), cortisol 21.3 microg/dL at 11 p.m. (half of normal morning value).
      Right pituitary macroadenoma was diagnosed through a series of dexamethasone
      tests and MRI. The patient received staging surgery including transsphenoidal
      adenomectomy and right frontotemporal craniotomy. As a result, the patient's
      physical condition gradually improved, and her menstrual cycle became regular
      with medication after the operation in the outpatient follow-up. CONCLUSION: PCOS
      is a common disease resulting in secondary amenorrhea. However, Cushing's
      syndrome resulting from pituitary macroadenoma should also be considered.
      Therefore, a careful history, observation, physical examination, and endocrine
      studies can differentiate between patients with PCOS and Cushing's disease.

PMID- 17197365
TI  - Acute viral hepatitis C-induced jaundice in pregnancy.
AB  - OBJECTIVE: Acute viral hepatitis C-induced jaundice in pregnancy is very rare and
      may be fatal. Here, we report a complicated case with acute hepatitis C-induced
      jaundice in pregnancy with successful management. CASE REPORT: A 27-year-old
      pregnant woman, gravida 2, para 1, with gestational age of 36 weeks and 5 days,
      was referred to our hospital due to jaundice and elevated liver enzymes of
      undetermined cause. She had been suffering from general weakness, diarrhea and
      vomiting for 1 week, and jaundice with tea-colored urine for 3 days. At our
      medical center, acute viral hepatitis C-induced jaundice was suspected. Since her
      general condition deteriorated at 36 weeks and 6 days of gestation, we decided to
      induce labor. A male baby was born smoothly via the vaginal route, with birth
      weight 2,857 g, birth length 48.6 cm, and 1- and 5-minute Apgar scores of 7 and
      9, respectively. Maternal condition improved dramatically after delivery and her
      serum liver enzymes and bilirubin levels gradually approached normal ranges.
      CONCLUSION: Mothers and fetuses with acute viral hepatitis C-induced jaundice
      during pregnancy are at great risk of mortality and morbidity. Timely termination
      may be one of the choices of treatment when fetal maturity has been reached and
      the maternal condition has deteriorated.

PMID- 17197366
TI  - Preservation of uterine integrity via transarterial embolization under
      postoperative massive vaginal bleeding due to cesarean scar pregnancy.
AB  - OBJECTIVE: Cesarean scar pregnancy (CSP) is an uncommon type of ectopic
      pregnancy. It results in uterine rupture and severe hemorrhage during the
      proceeding gestation. Whether diagnosed early or not, it may cause maternal
      mortality or morbidity during emergency management. Life-saving emergency
      hysterectomy is usually the treatment of choice when there is profuse bleeding
      intraoperatively or after initial management. CASE REPORT: A 38-year-old woman
      with a history of two previous cesarean deliveries was referred to our clinic
      under the impression of CSP at 11 weeks' gestation. A viable embryo with a crown
      rump length of 4.8 cm in the anterior wall of the uterus at the cervico-isthmic
      region was detected. Under the confirmation of CSP via ultrasonography, she was
      admitted for management. During hysterotomy, profuse bleeding with 1,000 mL blood
      loss was noted. After conservative procedure for hemostasis, however, massive
      vaginal bleeding persisted. As a result, we immediately transferred the patient
      to receive transarterial embolization (TAE) for bleeding control. The patient was
      discharged 4 days after the operation and TAE and her period resumed 1 month
      later. CONCLUSION: Management of CSP is usually accompanied by profuse blood
      loss. Hysterectomy is inevitable if massive blood loss occurs during surgical
      intervention. For preservation of fertility and avoidance of mortality, our
      physicians offered an alternative life-saving policy even under catastrophic
      blood loss.

PMID- 17197367
TI  - Dopaminergic dysbalance in distinct basal ganglia neurocircuits: implications for
      the pathophysiology of Parkinson's disease, schizophrenia and attention deficit
      hyperactivity disorder.
AB  - The basal ganglia form a forebrain system that collects signals from a large part
      of the neocortex, redistributes these cortical inputs both with respect to one
      another and with respect to inputs from the limbic system, and then focuses the
      inputs of this redistributed, integrated signals into particular regions of the
      frontal lobes and brainstem involved in aspects of motor planning and motor
      memory. Movement disorders associated with basal ganglia dysfunction comprise a
      spectrum of abnormalities that range from the hypokinetic disorder (from which
      Parkinson's disease, PD, is the best-known-example) at one extreme to the
      hyperkinetic disorder (exemplified by Huntington's disease and hemiballism) at
      the other. In addition to disorders of movement, major mental disorders including
      schizophrenic-like states and attention deficit hyperactivity disorder (ADHD)
      have been linked to abnormalities in the basal ganglia and their allied nuclei.
      In this paper we discuss recent evidence indicating that a dopamine-induced
      dysbalance of basal ganglia neurocircuitries may be an important
      pathophysiological component in PD, schizophrenia and ADHD. According to our
      model, the deprivation of dopaminergic nigro-striatal input, as in PD, reduces
      the positive feedback via the direct system, and increases the negative feedback
      via the indirect system. The critical consequences are an overactivity of the
      basal ganglia output sites with the resulting inhibition of thalamo-cortical
      drive. In schizophrenia the serious cognitive deficits might be partly a result
      of a hyperactivity of the inhibitory dopamine D(2) transmission system. Through
      this dysinhibition, the thalamus exhibits hyperactivity that overstimulates the
      cortex resulting in dysfunctions of perception, attention, stimulus distinction,
      information processing and affective regulation (inducing hallucinations and
      delusions) and motor disabilities. Recent studies have strongly suggested that a
      disturbance of the dopaminergic system is also involved in the pathophysiology of
      ADHD. The most convincing evidence comes from the demonstration of the efficacy
      of psychostimulants such as the dopamine transporter (DAT) blocker
      methylphenidate in the symptomatic treatment of ADHD. Genetic studies have shown
      an association between ADHD and genes involved in dopaminergic neurotransmission
      (for example the dopamine receptor genes DRD4 and DRD5, and the DAT gene DAT1).
      DAT knockout mice display a phenotype with increased locomotor activity, which is
      normalized by psychostimulant treatment. Finally, imaging studies demonstrated an
      increased density of DAT in the striatum of ADHD patients. Which system is
      disturbed and whether this system is hyper- or hypoactive is not unambiguously
      known yet.

PMID- 17197368
TI  - Implications of co-morbidity for etiology and treatment of neurodegenerative
      diseases with multifunctional neuroprotective-neurorescue drugs; ladostigil.
AB  - The recent therapeutic approach in which drug candidates are designed to possess
      diverse pharmacological properties and act on multiple targets has stimulated the
      development of several multifunction drugs. These include ladostigil (TV3326) [(N
      propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate], which combines the
      pharmacophore-neuroprotective effects of rasagiline, a selective monoamine
      oxidase (MAO)-B inhibitor, with the cholinesterase (ChE) inhibitory activity of
      rivastigmine or iron chelating moiety such as M30. In the case of M30 the
      pharmacophore of brain permeable iron chelator VK-28 plus the MAO inhibitor
      neuroprotective propargylamine moiety of rasagiline are combined in a single
      molecule as a potential treatment for Alzheimer's disease, Lewy body disease, and
      Parkinson's disease with dementia. Here, we discuss the activities of ladostigil
      in terms of its cholinesterase cognitive enhancing potential, antiParkinson,
      antidepressant, neuroprotection and APP (amyloid precursor protein) processing
      potential. One major attribute of ladostigil is its neuroprotective activity in
      neuronal cell cultures and in vivo. Employing an apoptotic model of neuroblastoma
      SK-N-SH cells, the molecular mechanism of its neuroprotective activity has been
      determined. The current studies show that ladostigil significantly decreased
      apoptosis via inhibition of the cleavage and prevention of caspase-3 activation
      through a mechanism related to regulation of the Bcl-2 family proteins, resulting
      in reduced levels of Bad and Bax and induced levels of Bcl-2. In addition,
      ladostigil elevated the levels of pPKC(pan). We have also followed the regulation
      of APP processing and found that ladostigil markedly decreased apoptotic-induced
      levels of holo-APP, as well as stimulated the release of the non-amyloidogenic
      soluble APP (sAPPalpha) into the conditioned medium via a established protein
      kinsae C-MAPkinase dependent pathway. Similar to ladostigil, its S-isomer,
      TV3279, which is a ChE inhibitor lacking MAO inhibitory activity, exerted similar
      neuroprotective properties and APP processing, suggesting that the mode of action
      is independent of MAO inhibition. These effects were shown to reside in the
      propargylamine moiety. These findings indicate that the dual actions of the anti
      apoptotic-neuroprotective activity and the ability to modulate APP processing,
      could make ladostigil a potentially valuable drug for the treatment of
      Alzheimer's disease.

PMID- 17197369
TI  - Common efficacy of psychotropic drugs in restoring stress-induced impairment of
      prefrontal plasticity.
AB  - We recently investigated the effects of stress on synaptic plasticity in the
      prefrontal cortex, namely the prelimbic area or the apparent homologue of the
      primate subgenual prefrontal cortex in humans where most of the hippocampal
      terminal fields are localized. Exposure to an acute stress causes a remarkable
      and long-lasting inhibition of long term potentiation (LTP) in the frontal cortex
      evoked by stimulation of hippocampal outflow and this impairment is prevented by
      the glucocorticoid receptor antagonist mifepristone. Thus, the frontal cortex is
      also a target for glucocorticoids involved in the stress response. Current data
      show that antidepressants of various types, i.e., tianeptine and fluoxetine, at
      doses normally used in antidepressant testing, restore LTP impaired by prior
      acute stress. Interestingly, clozapine administered in a similar way after stress
      rapidly reverses the stress-induced impairment of LTP at doses which do not
      affect LTP alone. This stress paradigm highlights comorbidity for both etiology
      and treatment of psychiatric disorders like depression and schizophrenia.
      Restoring appropriate cognitive functions in circuits associated with
      dysfunctions in coping with stress may be proposed as a new systems-level
      approach to drug discovery and development. We are presently investigating the
      involvement of signalling molecules in producing these plastic changes.

PMID- 17197370
TI  - Dopamine and incentive learning: a framework for considering antipsychotic
      medication effects.
AB  - Hyperfunction of brain dopamine (DA) systems is associated with psychosis in
      schizophrenia and the medications used to treat schizophrenia are DA receptor
      blockers. DA also plays a critical role in incentive learning produced by
      rewarding stimuli. Using DA as the link, these results suggest that psychosis in
      schizophrenia can be understood from the point of view of excessive incentive
      learning. Incentive learning is mediated through the non-declarative memory
      system and may rely on the striatum or medial prefrontal cortex depending on the
      task. Typical and atypical antipsychotics differentially affect expression of the
      immediate early gene c-fos, producing greater activity in the striatum and medial
      prefrontal cortex, respectively. This led to the hypothesis that performance of
      schizophrenic patients on tasks that depend on the striatum or medial prefrontal
      cortex will be differentially affected by their antipsychotic medication. Results
      from a number of published papers supported this dissociation. Furthermore, the
      effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were
      different from another atypical, risperidone that resembles the typical
      antipsychotics. Similarly, in tests of incentive learning, risperidone acted like
      the typical antipsychotics. Thus, typical and atypical antipsychotic drugs
      differed in the types of cognitive performance they affected and, furthermore,
      members of the atypical class differed in their effects on cognition. It remains
      the task of researchers and clinicians to sort out the symptoms associated with
      the endogenous illness from possible iatrogenic symptoms resulting from the
      antipsychotic medications used to treat schizophrenia.

PMID- 17197371
TI  - The family of sensorimotor gating disorders: comorbidities or diagnostic
      overlaps?
AB  - Prepulse inhibition (PPI) of startle is an operational measure of the pre
      attentive filtering process known as sensorimotor gating. Originally identified
      in patients with schizophrenia, PPI deficits have been observed in multiple but
      not all psychiatric disorders. Thus, as with most signs and symptoms of
      psychiatric disorders, deficits in PPI cut across diagnostic categories. It
      remains unclear whether the diversity of disorders exhibiting deficient PPI
      bespeaks diagnostic overlaps or comorbidities. Given the recent focus on
      treatments for cognitive deficits of schizophrenia independently of treating
      psychosis, the relationship of PPI deficits to cognitive deficits becomes of
      interest. Although PPI cannot be considered to be a cognitive process per se,
      abnormalities in pre-attentive information processing may be predictive of or
      lead to complex cognitive deficits. Animal models of PPI deficits produced by
      dopamine agonists reliably predict existing antipsychotics. Nevertheless, since
      neither PPI nor cognitive deficits in schizophrenia are ameliorated by standard
      antipsychotics, current research is exploring the predictive value of non
      dopaminergic PPI models in identifying treatments for gating disturbances
      independently of their relevance to specific disorders. Both PPI and cognitive
      deficits in schizophrenia patients are not reversed by first generation
      antipsychotics but may be attenuated by clozapine. Similarly, effects of
      glutamate antagonists on symptoms in patients and PPI in animals appear to be
      reduced by clozapine. Hence, treatment-induced reversals of deficits in PPI
      produced by glutamate antagonists may provide animal, and human, models to aid in
      the discovery of treatments of cognitive deficits in patients already treated
      with existing antipsychotics.

PMID- 17197372
TI  - Substance use disorders and Schizophrenia: a question of shared glutamatergic
      mechanisms.
AB  - Schizophrenia is noted for the remarkably high prevalence of substance use
      disorders (SUDs) including nicotine (>85%), alcohol and stimulants. Mounting
      evidence supports the hypothesis that the endophenotype of schizophrenia involves
      hypofunction of a subpopulation of cortico-limbic NMDA receptors. Low doses of
      NMDA receptor antagonists such as ketamine replicate in normal volunteers
      positive, negative and cognitive symptoms of schizophrenia as well as associated
      physiologic abnormalities such as eye tracking and abnormal event related
      potentials. Genetic studies have identified putative risk genes that directly or
      indirectly affect NMDA receptors including D-amino acid oxidase, its modulator
      G72, proline oxidase, mGluR3 and neuregulin. Clinical trials have shown that
      agents that directly or indirectly enhance the function of the NMDA receptor at
      its glycine modulatory site (GMS) reduce negative symptoms and in the case of D
      serine and sarcosine improve cognition and reduce positive symptoms in
      schizophrenic subjects receiving concurrent anti-psychotic medications. Notably,
      the GMS partial agonist D-cycloserine exacerbates negative symptoms in clozapine
      responders whereas full agonists, glycine and D-serine have no effects,
      suggesting clozapine may act indirectly as a full agonist at the GMS of the NMDA
      receptor. Clozapine treatment is uniquely associated with decreased substance use
      in patients with schizophrenia, even without psychologic intervention. Given the
      role of NMDA receptors in the reward circuitry and in substance dependence, it is
      reasonable to speculate that NMDA receptor dysfunction is a shared pathologic
      process in schizophrenia and co-morbid SUDs.

PMID- 17197374
TI  - Importance of clinical diagnoses for comorbidity studies in substance use
      disorders.
AB  - Many clinical and epidemiologic studies have shown a high frequency of co
      occurrence of substance abuse and psychiatric disorders, with important
      consequences from health and social perspective. However, the identification of
      reliable and valid diagnosis of psychiatric comorbidity in substance abusers is
      problematic, mainly because the acute or chronic effects of substance abuse can
      mimic symptoms of many other mental disorders, making difficult to differentiate
      psychiatric symptoms that represent effects of acute or chronic substance use or
      withdrawal, of those that represent an independent disorder. While DSM-IIII-R and
      earlier nomenclatures were unclear in differentiating independent from other
      psychiatric disorders, DSM-IV and DSM-IV-TR provided clearer guidelines in
      diagnosing psychiatric disorders in heavy users of alcohol and drugs, providing
      three categories: "primary" psychiatric disorders, "substance-induced" disorders,
      and "expected effects" of the substances, meaning expected intoxication and/or
      withdrawal symptoms that should not be diagnosed as symptoms of a psychiatric
      disorder. The use of the "Psychiatric Research Interview for Substance and Mental
      Disorders (PRISM)", a structured interview developed to improve the diagnosis of
      co morbidity in drug abusers according DSM-IV, supplies new opportunities in the
      clinical research in this field.

PMID- 17197373
TI  - The vulnerability to alcohol and substance abuse in individuals diagnosed with
      schizophrenia.
AB  - Individuals with schizophrenia are at increased risk for developing substance
      abuse disorders. Here, we consider factors that might elevate their risk for
      substance abuse. The tendency among schizophrenic individuals to overvalue drug
      like rewards and to devalue the potential negative consequences of substance
      abuse may be a contributing factor to their substance abuse risk. This bias,
      which may partly reflect the convergence of glutamatergic and dopaminergic input
      to the limbic striatum, also may contribute to disadvantageous decision-making
      and other impulsive behavior. This propensity to seek drug-like rewards is
      augmented by alterations in nicotinic cholinergic, GABAergic, glutamatergic, and
      cannabinnoid receptor function associated with schizophrenia that increase the
      abuse liability of low doses of nicotine, ethanol, and perhaps cannabis, and
      augment the dysphoric effects of higher doses of ethanol and cannabis. The
      distortions in reward processing and altered response to substances of abuse also
      increase the likelihood that individuals with schizophrenia will self-medicate
      their subjective distress with abused substances. The focus on distinctions
      between motivation and reward with respect to substance abuse risk by
      schizophrenic patients suggests a need for a reconsideration of the construct of
      "negative symptoms" for this dually-diagnosed patient group.

PMID- 17197376
TI  - No virological failure in semen during properly suppressive antiretroviral
      therapy despite subtherapeutic local drug concentrations.
AB  - PURPOSE: The aim of the study was to investigate whether drug resistance occurs
      earlier in seminal than in blood plasma with the use of such HAART regimens, of
      which only the two NRTIs achieve therapeutic concentrations in seminal plasma.
      METHOD: Seminal and blood plasma of 12 patients, for 48-96 weeks on suppressive
      first-line therapy with saquinavir/ritonavir/didanosine/lamivudine,
      nelfinavir/didanosine/stavudine, or efavirenz/lamivudine/zidovudine were
      prospectively evaluated for HIV-1-RNA resistance mutations and drug
      concentrations. RESULTS: Saquinavir, nelfinavir, and efavirenz blood plasma
      concentrations were in the therapeutic range. Nelfinavir and efavirenz seminal
      plasma concentrations were below the limit of quantification. In only 2 of 9
      seminal plasma samples, from 1 of 6 patients, the saquinavir concentration was
      above the minimum therapeutic level. The seminal plasma HIV-1-RNA concentration
      remained undetectable in all patients up to 96 weeks, and therefore drug
      resistance could not be demonstrated. Thus, despite suboptimal local drug
      concentrations, no virological failure occurred in seminal plasma after prolonged
      first-line HAART. CONCLUSION: This finding supports the hypothesis that the
      source of HIV in semen is a spillover from the blood/extraluminal tissue and that
      therefore seminal plasma drug levels may not be critical for viral suppression
      within the lumen of the male genital tract.

PMID- 17197377
TI  - Substitution with lopinavir/ritonavir improves patient-reported outcomes
      including quality of life in patients who were intolerant to their antiretroviral
      therapy.
AB  - PURPOSE: Adverse effects are important determinants of quality of life (QOL)
      during highly active antiretroviral therapy (HAART). The PLATO study investigated
      the association between changes in patient-reported outcomes including QOL and
      substitution with lopinavir/ritonavir in patients experiencing side effects
      (SEs). METHOD: HIV-1-infected participants (N = 849) with undetectable viral load
      experiencing Grade-2 SEs of the protease inhibitor (PI) or nonnucleoside reverse
      transcriptase inhibitor (NNRTI) component of their HAART regimen were randomized
      to immediate (baseline) or deferred (week 4) substitution with
      lopinavir/ritonavir soft-gel capsules 400/100 mg bid. The primary endpoint was
      change in the total score from the AIDS Clinical Trials Group (ACTG) Symptoms
      Distress Module (ASDM), supplemented with two items for nephrolithiasis.
      Secondary endpoints included Medical Outcomes Study (MOS)-HIV scores and Center
      for Epidemiologic Studies-Depression (CES-D) scores. RESULTS: Immediate
      substitution resulted in improved ASDM total score at week 4 compared with
      deferred substitution (p <.001) and significant improvements in all MOS-HIV
      domains, while significant improvement was observed in CES-D scores at week 8.
      Primary SEs resolved at week 8 in 65% of participants in the immediate
      substitution group. Suppression of HIV-1 was maintained. Treatment was well
      tolerated and associated with elevations in cholesterol and triglycerides.
      CONCLUSION: Substitution with LPV/r improved patient-reported outcomes including
      QOL in patients experiencing Grade-2 SEs, while maintaining viral suppression.

PMID- 17197378
TI  - Cost to achieve an undetectable viral load using recommended antiretroviral
      regimens.
AB  - PURPOSE: The April 2005 Guidelines for the Use of Antiretroviral Agents in HIV
      Infected Adults and Adolescents recommended 9 regimens to be combined with 2
      nucleoside reverse transcriptase inhibitors (NRTIs). These regimens are effective
      in lowering viral load but are expensive. This study aimed to determine the cost
      for each regimen to achieve an undetectable viral load. METHOD: 52 clinical
      trials were reviewed. The outcome measure was cost per undetectable patient,
      C/PU, where C = cost of a drug, and PU = percent of patients with undetectable
      viral loads. RESULTS: For 30 weeks, cost per undetectable (<400 copies/mL) ranged
      from 4,416 dollars (efavirenz) to 23,110 dollars (nelfinavir); for 42 weeks, the
      range was 5,729 dollars (efavirenz) to 24,071 dollars (indinavir/ritonavir); for
      60 weeks, it ranged from 9,535 dollars (efavirenz) to 26,829 dollars
      (fosamprenavir); and for 84 weeks, it ranged from 12,203 dollars (efavirenz) to
      22,960 dollars (nelfinavir). For <50 copies/mL, at 30 weeks the range was from
      7,140 dollars (efavirenz) to 17,548 dollars (atazanavir); for 42 weeks, it ranged
      from 9,849 dollars (lopinavir/ritonavir) to 13,181 dollars (nelfinavir); for 60
      weeks, it ranged from 8,702 dollars (nevirapine) to 36,034 dollars (atazanavir);
      and for 84 weeks, it ranged from 15,660 dollars (efavirenz) to 29,177 dollars
      (indinavir/ritonavir). CONCLUSION: Efavirenz's low price and high effectiveness
      make it the least expensive means of achieving an undetectable viral load.

PMID- 17197379
TI  - Low incidence of severe liver events in HIV patients with and without hepatitis C
      or B coinfection receiving lopinavir/ritonavir.
AB  - OBJECTIVES: To analyze the incidence of severe liver events in HIV patients
      treated with lopinavir/ritonavir and the role of coinfection in the development
      of this toxicity. METHOD: This was a retrospective, multicenter, cohort study of
      all HIV-positive patients who started a regimen of HAART that included
      lopinavir/ritonavir (LPV/r). The main outcome variable was the emergence of a
      severe liver event, defined as decompensation of pre-existing chronic liver
      disease and grade 3-4 hypertransaminasemia (HT), that is, plasma AST or ALT
      values >5 times above the upper limit of normality, if baseline levels were
      normal, or >3.5 times the baseline values when they were abnormal. RESULTS: 388
      HIV-infected patients were included, with a median follow-up of 25.6 months.
      Coinfection with HCV was present in 61% of the patients and with HBV in 6.7%.
      There were 6 cases of severe liver events, all involving patients who were
      coinfected with HCV and all within the first 6 months. This represents 0.72
      events per 100 patient-years (95% confidence interval [CI] 0.36-2.98) and 1.21
      events per 100 patient-years (95% CI 0.60-5.86) in coinfected patients. The only
      factors associated with severe liver events at 6 months were baseline HT and HCV
      coinfection. CONCLUSION: The incidence of severe hepatic events in HIV-positive
      patients receiving a HAART regimen including LPV/r was very low, even in
      coinfected patients. HCV coinfection and baseline HT were the only factors
      associated with severe liver events. LPV/r can be considered a safe and well
      tolerated option in HIV patients with hepatotropic virus coinfections.

PMID- 17197375
TI  - Neurotoxins and neurotoxicity mechanisms. An overview.
AB  - Neurotoxins represent unique chemical tools, providing a means to 1) gain insight
      into cellular mechanisms of apopotosis and necrosis, 2) achieve a morphological
      template for studies otherwise unattainable, 3) specifically produce a singular
      phenotype of denervation, and 4) provide the starting point to delve into
      processes and mechanisms of nerve regeneration and sprouting. There are many
      other notable uses of neurotoxins in neuroscience research, and ever more being
      discovered each year. The objective of this review paper is to highlight the
      broad areas of neuroscience in which neurotoxins and neurotoxicity mechanism come
      into play. This shifts the focus away from neurotoxins per se, and onto the major
      problems under study today. Neurotoxins broadly defined are used to explore
      neurodegenerative disorders, psychiatric disorders and substance use disorders.
      Neurotoxic mechanisms relating to protein aggregates are indigenous to Alzheimer
      disease, Parkinson's disease. NeuroAIDS is a disorder in which microglia and
      macrophages have enormous import. The gap between the immune system and nervous
      system has been bridged, as neuroinflammation is now considered to be part of the
      neurodegenerative process. Related mechanisms now arise in the process of
      neurogenesis. Accordingly, the entire spectrum of neuroscience is within the
      purview of neurotoxins and neurotoxicity mechanisms. Highlights on discoveries in
      the areas noted, and on selective neurotoxins, are included, mainly from the past
      2 to 3 years.

PMID- 17197380
TI  - Fosamprenavir clinical study meta-analysis in ART-naive subjects: rare occurrence
      of virologic failure and selection of protease-associated mutations.
AB  - BACKGROUND: In recent ritonavir-boosted protease inhibitor (PI) studies, high
      efficacy rates have been observed, with few PI mutations detected. METHOD: To
      better understand the types of mutations observed and their phenotypic impact and
      the likelihood of virologic failure (VF) on a regimen that includes either a
      ritonavir-boosted or unboosted PI, fosamprenavir, a meta-analysis of three
      studies (NEAT, SOLO, and KLEAN) of 922 ART-naive participants receiving boosted
      (FPV/r) or unboosted fosamprenavir (FPV) plus abacavir/lamivudine was performed.
      70% of participants by the missing and discontinuation equals failure analysis
      and 95% by the observed analysis had HIV-RNA <400 copies/mL through 48 weeks.
      Paired genotypes (baseline and follow-up) were obtained for 74/85 participants
      meeting VF analysis criteria. RESULTS: FPV-associated resistance mutations were
      detected in 5/74 patients with VF, with 4/5 receiving unboosted FPV; in four
      patients viruses developed I54L or M and one developed the V32I+I47V combination.
      No virus from patients with VF receiving FPV/r had reduced FPV susceptibility
      (RS), whereas virus from 3/4 of participants with VF who received unboosted FPV
      and who acquired FPV mutations had FPV RS. Little PI cross-resistance was
      detected in the VF virus; RS was observed for lopinavir, saquinavir, nelfinavir,
      atazanavir, and indinavir in 0, 0, 2, 0, and 1 of 5 subjects, respectively.
      CONCLUSION: These data suggest that inclusion of FPV as part of an initial HIV
      treatment regimen is associated with low rates of VF. Selection of FPV resistance
      associated mutations is unlikely, especially for FPV/r-containing regimens. If
      selection of FPV-associated mutations does occur, a second-line PI-containing
      regimen can be easily constructed.

PMID- 17197382
TI  - Reduced rather than enhanced cholinergic airway constriction in mice with
      ablation of the large conductance Ca2+-activated K+ channel.
AB  - The unique voltage- and Ca2+-dependent K+ (BK) channel, prominently expressed in
      airway smooth muscle cells, has been suggested as an important effector in
      controlling airway contractility. Its deletion in mice depolarized resting
      membrane potential of tracheal cells, suggesting an increased open-probability of
      voltage-gated Ca2+ channels. While carbachol concentration-dependently increased
      the tonic tension of wild-type (WT) trachea, mutant trachea showed a different
      response with rapid tension development followed by phasic contractions
      superimposed on a tonic component. Tonic contractions were substantially more
      dependent on L-type Ca2+ current in mutant than in WT trachea, even though L-type
      Ca2+ channels were not up-regulated. In the absence of L-type Ca2+ current, half
      maximal contraction of trachea was shifted from 0.51 to 1.7 microM. In agreement,
      cholinergic bronchoconstriction was reduced in mutant lung slices, isolated
      perfused lungs and, most impressively, in mutant mice analyzed by body
      plethysmography. Furthermore, isoprenaline-mediated airway relaxation was
      enhanced in mutants. In-depth analysis of cAMP and cGMP signaling revealed up
      regulation of the cGMP pathway in mutant tracheal muscle. Inhibition of cGMP
      kinase reestablished normal sensitivity toward carbachol, indicating that up
      regulation of cGMP signaling counterbalances for BK channel ablation, pointing to
      a predominant role of BK channel in regulation of airway tone.

PMID- 17197383
TI  - Ligand-induced down-regulation of the cannabinoid 1 receptor is mediated by the G
      protein-coupled receptor-associated sorting protein GASP1.
AB  - The cannabinoid 1 receptor (CB1R) is one of the most abundant seven transmembrane
      (7TM) spanning/G-protein-coupled receptors in the central nervous system and
      plays an important role in pain transmission, feeding, and the rewarding effects
      of cannabis. Tolerance to cannabinoids has been widely observed after long-term
      use, with concomitant receptor desensitization and/or down-regulation depending
      on the brain region studied. Several CB1R agonists promote receptor
      internalization after activation, but the postendocytic sorting of the receptor
      has not been studied in detail. Utilizing human embryonic kidney (HEK293) cells
      stably expressing the CB1R and primary cultured neurons expressing endogenous
      CB1R, we show that treatment with cannabinoid agonists results in CB1R
      degradation after endocytosis and that the G-protein-coupled receptor-associated
      sorting protein GASP1 plays a major role in the postendocytic sorting process.
      Thus, these results may identify a molecular mechanism underlying tolerance and
      receptor down-regulation after long-term use of cannabinoids.

PMID- 17197384
TI  - Fabrication of 3D hepatic tissues by additive photopatterning of cellular
      hydrogels.
AB  - We have fabricated a hepatic tissue construct using a multilayer photopatterning
      platform for embedding cells in hydrogels of complex architecture. We first
      explored the potential of established hepatocyte culture models to stabilize
      isolated hepatocytes for photoencapsulation (e.g., double gel, Matrigel,
      cocultivation with nonparenchymal cells). Using photopolymerizable PEG hydrogels,
      we then tailored both the chemistry and architecture of the hydrogels to further
      support hepatocyte survival and liver-specific function. Specifically, we
      incorporated adhesive peptides to ligate key integrins on these adhesion
      dependent cells. To identify the appropriate peptides for incorporation, the
      integrin expression of cultured hepatocytes was monitored by flow cytometry and
      their functional role in cell adhesion was assessed on full-length extracellular
      matrix (ECM) molecules and their adhesive peptide domains. In addition, we
      modified the hydrogel architecture to minimize barriers to nutrient transport for
      these highly metabolic cells. Viability of encapsulated cells was improved in
      photopatterned hydrogels with structural features of 500 microm in width over
      unpatterned, bulk hydrogels. Based on these findings, we fabricated a multilayer
      photopatterned PEG hydrogel structure containing the adhesive RGD peptide
      sequence to ligate the alpha5beta1 integrin of cocultured hepatocytes. Three
      dimensional photopatterned constructs were visualized by digital volumetric
      imaging and cultured in a continuous flow bioreactor for 12 d where they
      performed favorably in comparison to unpatterned, unperfused constructs. These
      studies will have impact in the field of liver biology as well as provide
      enabling tools for tissue engineering of other organs.

PMID- 17197386
TI  - Analog of H2 relaxin exhibits antagonistic properties and impairs prostate tumor
      growth.
AB  - Hormone antagonists can be effective tools to delineate receptor signaling
      pathways and their resulting downstream physiological actions. Mutation of the
      receptor binding domain (RBD) of human H2 relaxin (deltaH2) impaired its
      biological function as measured by cAMP signaling. In a competition assay,
      deltaH2 exhibited antagonistic activity by blocking recombinant H2 relaxin from
      binding to receptors on THP-1 cells. In a flow cytometry-based binding assay,
      deltaH2 demonstrated weak binding to 293T cells expressing the LGR7 receptor in
      the presence of biotinylated H2 relaxin. When human prostate cancer cell lines
      (PC-3 and LNCaP) were engineered to overexpress eGFP, wild-type (WT) H2, or
      deltaH2, and subsequently implanted into NOD/SCID mice, tumor xenografts
      overexpressing deltaH2 displayed smaller volumes compared to H2 and eGFP
      controls. Plasma osmolality readings and microvessel density and area assessment
      suggest that deltaH2 modulates physiological parameters in vivo. In a second
      murine model, intratumoral injections of lentivectors engineered to express
      deltaH2/eGFP led to suppressed tumor growth compared to controls. This study
      provides further evidence supporting a role for H2 relaxin in prostate tumor
      growth. More importantly, we report how mutation of the H2 relaxin RBD confers
      the hormone derivative with antagonistic properties, offering a novel reagent for
      relaxin research.

PMID- 17197385
TI  - Molecular programming of endothelin-1 in HIV-infected brain: role of Tat in up
      regulation of ET-1 and its inhibition by statins.
AB  - Human Immune Deficiency Virus-1 (HIV-1) infection can induce severe and
      debilitating neurological problems, including behavioral abnormalities, motor
      dysfunction, and dementia. HIV can persistently infect astrocytes, during which
      viral accessory proteins are produced that are unaffected by current
      antiretroviral therapy. The effect of these proteins on astrocyte function
      remains unknown. Astrocytes are the predominant cells within the brain; thus,
      disruption of astrocyte function could influence the neuropathogenesis of HIV
      infection. To explore further these effects, we constitutively expressed HIV-Tat
      protein in astrocytes. Since the nuclear presence of Tat protein leads to
      alteration of host gene expression, we further analyzed the effects of Tat on
      host gene transcripts. Endothelin-1 (ET-1) was a significantly elevated
      transcript as verified by reverse transcription-polymerase chain reaction (RT
      PCR), and it was subsequently released extracellularly in Tat-expressing and HIV
      infected astrocytes. ET-1 expression was also prominent in reactive astrocytes
      and neurons in brain tissues from basal ganglia and frontal lobes of HIV
      encephalitic patients. HIV-Tat regulated ET-1 at the transcriptional level
      through NF-kappaB (NF-kappaB)-responsive sites in the ET-1 promoter.
      Intriguingly, simvastatin (10 microM) down-regulated HIV-Tat-induced ET-1 and
      also inhibited activation of NF-kappaB in astrocytes. Our findings suggest that
      ET-1 may be critical in mediating the neuropathogenesis of HIV dementia and that
      statins may have therapeutic potential in these patients.

PMID- 17197387
TI  - Cloning and functional characterization of a gamma-hydroxybutyrate receptor
      identified in the human brain.
AB  - Two parent clones of a gamma-hydroxybutyrate (GHB) receptor, C12K32 and GHBh1,
      were isolated from a human frontal cortex cDNA library. The two clones differ by
      a deleted cytosine in C12K32. CHO cells transfected with either C12K32 or GHBh1
      responded positively to submicromolar GHB stimulation. However, unlike C12K32,
      GHBh1 desensitizes rapidly on application of low concentrations of GHB. GHB
      receptor properties were then studied on C12K32 expressed in CHO cells. C12K32
      bound GHB with a Kd of 114 nM and has no affinity for GABA or glutamate. GHB and
      NCS-382 displaced [3H]GHB with an IC50 of 53 +/- 8 and 120 +/- 18 nM,
      respectively. In patch-clamp experiments, GHB induced a dose-dependent response
      with an EC50 of 130 nM. This response was antagonized by NCS-382, was not
      reproduced by GABA, and was sensitive to the addition of GTP-gamma-S in the
      recording pipette. CHO cells transfected with C12K32 exhibited GTPgamma-35S
      binding with an EC50 of 462 nM for GHB and an IC50 of 2.9 microM for NCS-382. The
      present data led to the conclusion that both C12K32 and GHBh1 are two closely
      related isoforms of a human GHB receptor, GHBh1, that is described in the
      databank as the GPCR 172A.

PMID- 17197388
TI  - Molecular regulation of the PAI-1 gene by hypoxia: contributions of Egr-1, HIF
      1alpha, and C/EBPalpha.
AB  - Hypoxia, as occurs during tissue ischemia, tips the natural
      anticoagulant/procoagulant balance of the endovascular wall to favor activation
      of coagulation. Plasminogen activator inhibitor-1 (PAI-1) is an important factor
      suppressing fibrinolysis under conditions of low oxygen tension. We previously
      reported that hypoxia induced PAI-1 mRNA and antigen expression in murine
      macrophages secondary to increased de novo transcription as well as increased
      mRNA stability. We now show in RAW264.7 murine macrophages that the transcription
      factors early growth response gene-1 (Egr-1), hypoxia-inducible factor-1alpha
      (HIF-1alpha), and CCAAT/enhancer binding protein alpha (C/EBPalpha) are quickly
      activated in hypoxia and are responsible for transcription and expression of PAI
      1. Murine PAI-1 promoter constructs, including Egr, HIF-1alpha, and/or C/EBPalpha
      binding sites, were transfected into RAW 264.7 murine macrophages. To identify
      the relative importance of each of these putative hypoxia-responsive elements,
      cells were exposed to normobaric hypoxia, and transcriptional activity was
      recorded. At 16 h of hypoxic exposure, murine PAI-1 promoter deletion constructs
      that included Egr, HIF-1alpha, and/or C/EBPalpha binding sites demonstrated
      increased transcriptional activity. Mutation of each of these three murine PAI-1
      promoter sites (or a combination of them) resulted in a marked reduction in
      hypoxia sensitivity as detected by transcriptional analysis. Functional data
      obtained using 32P-labeled Egr, HIF-1alpha response element (HRE), and C/EBPalpha
      oligonucleotides revealed induction of DNA binding activity in nuclear extracts
      from hypoxic RAW cells, with supershift analysis confirming activation of Egr-1,
      HIF-1alpha, or C/EBPalpha. ChIP analysis confirmed the authenticity of these
      interactions as each of these transcription factors binds to chromatin under
      hypoxic conditions. Further, the induction of PAI-1 by Egr-1, HIF-1alpha, or
      C/EBPalpha was replicated in primary peritoneal macrophages. These data suggest
      that although HIF-1alpha appears to dominate the PAI-1 transcriptional response
      in hypoxia, Egr-1 and C/EBPalpha greatly augment this response and can do so
      independent of HIF-1alpha or each other. These studies are relevant to ischemic
      up-regulation of the PAI-1 gene and consequent accrual of microvascular thrombus
      under ischemic conditions.

PMID- 17197389
TI  - Optical analysis of the HIF-1 complex in living cells by FRET and FRAP.
AB  - Hypoxia-inducible factor-1 (HIF-1) coordinates the cellular response to a lack of
      oxygen by controlling the expression of hypoxia-inducible genes that ensure an
      adequate energy supply. Assembly of the HIF-1 complex by its oxygen-regulated
      subunit HIF-1alpha and its constitutive beta subunit also known as ARNT is the
      key event of the cellular genetic response to hypoxia. By two-photon microscopy,
      we studied HIF-1 assembly in living cells and the mobility of fluorophore-labeled
      HIF-1 subunits by fluorescence recovery after photobleaching. We found a
      significantly slower nuclear migration of HIF-1alpha than of HIF-1beta,
      indicating that each subunit can move independently. We applied fluorescence
      resonance energy transfer to calculate the nanometer distance between alpha and
      beta subunits of the transcriptionally active HIF-1 complex bound to DNA. Both N
      termini of the fluorophore-labeled HIF-1 subunits were localized as close as 6.2
      nm, but even the N and C terminus of the HIF-1 complex were not further apart
      than 7.4 nm. Our data suggest a more compact 3-dimensional organization of the
      HIF complex than described so far by 2-dimensional models.

PMID- 17197390
TI  - The evolutionally conserved activity of Dapper2 in antagonizing TGF-beta
      signaling.
AB  - Dapper1 and Dapper2, two divergent members of the Dapper family, have been
      suggested to modulate Wnt and TGF-beta/Nodal signaling in Xenopus and zebrafish.
      To get a better understanding of Dapper function in mammals, we have cloned the
      mouse ortholog of zebrafish Dapper2, mDpr2 and investigated its function in
      regulating TGF-beta signaling activity. Here, we showed that, like zebrafish
      Dapper2, overexpression of mDpr2 inhibited the TGF-beta-induced expression of the
      Smad-responsive reporters and targeted TGF-beta type I receptor ALK5 for
      degradation in mammalian cells. Overexpression of mDpr2 in the zebrafish embryos
      led to a decrease in expression of the mesoderm marker no tail and goosecoid at
      the shield stage and eye fusion later, implying that mDpr2 may have an intrinsic
      in vivo activity similar to fish Dapper2 activity. The expression of mDpr2 was
      detected throughout the epiblast around the onset of gastrulation and in somites,
      the neural tube and gut at later stages in mouse embryos, implying a role in
      early embryonic development. Our data indicate that the function of Dpr2 as a
      negative regulator of the TGF-beta/Nodal signal pathway is evolutionally
      conserved, at least in part, in fish and mammals.

PMID- 17197391
TI  - Nitric oxide activation of peroxisome proliferator-activated receptor gamma
      through a p38 MAPK signaling pathway.
AB  - Both nitric oxide (NO*) and peroxisome proliferator-activated receptors (PPARs)
      protect the endothelium and regulate its function. Here, we tested for crosstalk
      between these signaling pathways. Human umbilical vein and hybrid EA.hy926
      endothelial cells were exposed to S-nitrosoglutathione (GSNO) or
      diethylenetriamine NONOate (DETA NONOate). Electrophoretic mobility shift assays
      using PPAR-response element (PPRE) probe showed that NO* caused a rapid dose
      dependent increase in PPARgamma binding, an effect that was confirmed in vivo by
      chromatin immunoprecipitation. Conversely, N(G)-monomethyl-L-arginine, a NOS
      inhibitor, decreased PPARgamma binding. NO*-mediated PPARgamma binding and NO*
      induction of cyclooxygenase-2 (COX-2), diacylglycerol (DAG) kinase alpha
      (DGKalpha), and heme oxygenase-1 (HO-1), genes with well-characterized PPRE
      motifs, were cGMP independent. NO* dose dependently activated p38 MAPK, and p38
      MAPK inhibition with SB202190 or knockdown with siRNA was shown to block NO*
      activation of PPARgamma. Likewise, p38 MAPK and PPARgamma inhibitors or knockdown
      of either transcript all significantly blocked NO* induction of PPRE-regulated
      genes. PPARgamma activation by p38 MAPK may contribute to the anti-inflammatory
      and cytoprotective effects of NO* in the vasculature. This crosstalk mechanism
      suggests new strategies for preventing and treating vascular dysfunction.

PMID- 17197392
TI  - You are what you cite: the role of references in scientific publishing.

PMID- 17197393
TI  - Inadequate training in the biological sciences and medicine for dental students:
      an impending crisis for dentistry.

PMID- 17197394
TI  - Perioral dermatitis.

PMID- 17197395
TI  - Occlusion and periodontal disease.

PMID- 17197396
TI  - Occlusal discrepancies.

PMID- 17197400
TI  - Comparison of the intakes of sugars by young children with and without dental
      caries experience.
AB  - BACKGROUND: Relationships among sugars and dental caries in contemporary
      societies are unclear. The authors describe young children's intakes of nonmilk
      extrinsic (NME) and intrinsic/milk sugars and relate those intakes to dental
      caries. METHODS: The authors conducted cross-sectional analyses of dietary data
      collected from the Iowa Fluoride Study using three-day diaries for subjects at
      ages 1, 2, 3, 4 and 5 years and for subjects aged 1 through 5 years according to
      dental caries experience at 4.5 to 6.9 years of age. They categorized foods and
      beverages as containing NME or intrinsic/milk sugars. RESULTS: Subjects' total,
      NME, food NME and intrinsic/milk sugars intakes at ages studied did not differ
      between subjects with and without caries experience. Beverage NME sugars intakes
      at age 3 years predicted caries (P < .05) in logistic regression models adjusted
      for age at dental examination and for fluoride intake. CONCLUSIONS: Dental caries
      is a complex, multifactorial disease process dependent on the presence of oral
      bacteria, a fermentable carbohydrate substrate and host enamel. A simple NME
      intrinsic/milk sugars categorization appears insufficient to capture the complex
      dietary component of the caries process. CLINICAL IMPLICATIONS: Cariogenicity is
      more likely a function of the food and/or beverage vehicle delivering the sugar
      and the nature of exposure-that is, frequency and length of eating events-than of
      the sugar's categorization.

PMID- 17197401
TI  - Chemomechanical caries removal in children: an operator's and pediatric patients'
      responses.
AB  - BACKGROUND: This study investigated an operator's and pediatric patients'
      responses to chemo-mechanical caries removal (CMCR) versus the traditional method
      (TM) of caries removal using a handpiece and a round bur when treating dentinal
      depth occlusal lesions with minimal enamel access in primary molars. METHODS:
      Data were collected from 50 children at baseline and before, during and after
      caries removal using CMCR or TM. The subjects in the CMCR group were on average
      younger than the subjects in the TM group and had more deep lesions. RESULTS: The
      operator rated CMCR as needing more clinical and technical effort and more total
      effort than TM. He was less satisfied with CMCR than with TM. Subjects in the
      CMCR group perceived the time needed for treatment as significantly longer than
      did the subjects in the TM group. Fear of the dentist decreased in subjects in
      the TM group from before to after the operative appointment, while it increased
      in subjects in the CMCR group. CONCLUSIONS: The authors found no direct advantage
      in using CMCR over using TM. CLINICAL IMPLICATIONS: CMCR cannot be recommended as
      an alternative to TM when treating dentinal depth occlusal lesions with minimal
      access in primary molars.

PMID- 17197402
TI  - The use of temporary anchorage devices for molar intrusion.
AB  - BACKGROUND: This article reviews the use of temporary anchorage devices (TADs)
      for maxillary molar intrusion. TYPES OF STUDIES REVIEWED: The authors reviewed
      clinical, radiographic and histologic studies and case reports. The studies
      provided information regarding the application, placement and biological response
      of orthodontic TADs. RESULTS: TAD-supported molar intrusion is controlled and
      timely and may be accomplished without the need for full-arch brackets and wires.
      Supraerupted maxillary first molars can be intruded 3 to 8 millimeters in 7.5
      months (approximately 0.5-1.0 mm per month), without loss of tooth vitality,
      adverse periodontal response or radiographically evident root resorption.
      CLINICAL IMPLICATIONS: True molar intrusion can be achieved successfully with
      orthodontic TADs, re-establishing a functional posterior occlusion and reducing
      the need for prosthetic crown reduction.

PMID- 17197403
TI  - Damage to the inferior alveolar nerve as the result of root canal therapy.
AB  - BACKGROUND: Endodontic treatment of mandibular molar teeth has the potential to
      damage the inferior alveolar nerve via direct trauma, pressure or neurotoxicity.
      METHODS: The author reviewed all cases of involvement of the inferior alveolar
      nerve resulting from root canal therapy in patients seen in a tertiary referral
      center during an eight-year period (1998 through 2005). The author had encouraged
      practitioners to refer patients immediately to a university clinic. RESULTS: The
      author saw 61 patients during the eight-year period. Eight patients were
      asymptomatic and received no treatment. Forty-two patients exhibited only mild
      symptoms or were seen more than three months after undergoing root canal therapy,
      and they received no surgical treatment. Only 10 percent of these patients
      experienced any resolution of symptoms. Eleven patients underwent surgical
      exploration. Five of these patients underwent exploration and received treatment
      within 48 hours, and all recovered completely. The remaining six patients
      underwent surgical exploration and received treatment between 10 days and three
      months after receiving endodontic therapy. Of these patients, four experienced
      partial recovery and two experienced no recovery at all. CONCLUSIONS: Early
      surgical exploration and debridement may reverse the side effects of endodontic
      treatment on the inferior alveolar nerve. CLINICAL IMPLICATIONS: If the
      radiograph obtained after endodontic therapy shows sealant in the inferior
      alveolar canal, then immediate referral to an oral and maxillofacial surgeon is
      indicated if the patient has continued symptoms of paresthesia or pain once the
      local anesthetic should have worn off. Immediate surgical exploration and
      debridement may provide satisfactory results.

PMID- 17197404
TI  - Nutrition and inflammatory markers.
AB  - BACKGROUND: Inflammation underlies many chronic diseases. The goal of nutritional
      support in such diseases is to provide adequate energy and nutrients to meet the
      increased requirements for synthesis of acute phase proteins, inflammatory
      mediators, antioxidant defenses and the promotion of tissue repair and
      restoration of cellular function. CONCLUSIONS: Systemic inflammation alters
      utilization of various nutrients (fats, carbohydrates and protein) and promotes
      increased cellular consumption of key antioxidant vitamins and minerals. Some
      nutrients play a direct role in the resolution of inflammation. These
      relationships necessitate consideration of the adjunctive role of diet in the
      natural history of periodontitis. CLINICAL IMPLICATIONS: Little is known about
      the role of nutrition in periodontitis. With rapid advances in molecular biology
      and nutritional genomics in particular, oral health scientists can address this
      important area of study.

PMID- 17197405
TI  - Craniofacial pain as the sole symptom of cardiac ischemia: a prospective
      multicenter study.
AB  - BACKGROUND: Craniofacial pain can be the only symptom of cardiac ischemia.
      Failure to recognize its cardiac source can put the patient's life at risk. The
      authors conducted a study to reveal the prevalence of, the distribution of and
      sex differences regarding craniofacial pain of cardiac origin. METHODS: The
      authors prospectively selected consecutive patients (N = 186) who had had a
      verified cardiac ischemic episode. They studied the location and distribution of
      craniofacial and intraoral pain in detail. RESULTS: Craniofacial pain was the
      only complaint during the ischemic episode in 11 patients (6 percent), three of
      them who had acute myocardial infarction (AMI). Another 60 patients (32 percent)
      reported craniofacial pain concomitant with pain in other regions. The most
      common craniofacial pain locations were the throat, left mandible, right
      mandible, left temporomandibular joint/ear region and teeth. Craniofacial pain
      was pre-ponderantly manifested in female subjects (P = .031) and was the
      dominating symptom in both sexes in the absence of chest pain. CONCLUSIONS:
      Craniofacial pain commonly is induced by cardiac ischemia. This must be
      considered in differential diagnosis of toothache and orofacial pain. CLINICAL
      IMPLICATIONS: Because patients who have AMI without chest pain run a higher risk
      of experiencing a missed diagnosis and death, the dentist's awareness of this
      symptomatology can be crucial for early diagnosis and timely treatment.

PMID- 17197406
TI  - The impact of oral disease and nonsurgical treatment on bacteremia in children.
AB  - BACKGROUND: The authors examine the role of dental disease and nonsurgical dental
      procedures in the incidence and duration of bacteremia in children. METHODS: The
      authors randomized a group of children to receive amoxicillin or a placebo before
      dental rehabilitation in an operating room setting. They collected eight blood
      draws at the following times: two minutes after intubation (draw 1); after dental
      restorations, pulp therapy and cleaning (draw 2); 10 minutes later (draw 3); and
      five draws during and after dental extractions (draws 4-8). The authors compared
      dental disease parameters and the type of dental procedures performed with the
      incidence and duration of bacteremia. RESULTS: The authors enrolled 100 children
      (aged 1-8 years) in the study. The incidence of bacteremia from draw 2 was 20
      percent in the placebo group and 6 percent in the amoxicillin group (P = .07),
      and the incidence from draw 3 was 16 percent in the placebo group and zero
      percent in the amoxicillin group (P = .03). Subjects with higher gingival scores
      were more likely to have a bacteremia for draw 2 (P = .01). The authors found
      that subjects in the group with bacteremia for draw 3 had undergone more
      pulpotomies than did subjects in the group without bacteremia for draw 3 (3 +/-
      2.5 standard deviation [SD] versus 1.5 +/- 1.6 SD, P = .04), while they found
      almost no differences for draw 2. CONCLUSIONS: This study suggests that gingival
      disease has an impact on bacteremia after dental restorations and prophylaxis.
      Although antibiotics have an impact, they do not eliminate bacteremia altogether.

PMID- 17197407
TI  - Reduced or painful jaw movement after collision-related injuries: a population
      based study.
AB  - BACKGROUND: The authors report the incidence of and factors associated with
      reduced and/or painful jaw movement after motor vehicle collisions that resulted
      in whiplash-associated disorders (WADs). METHODS: All adults filing collision
      related personal injury claims during an 18-month period in Saskatchewan, Canada,
      were evaluated via questionnaire to determine demographic characteristics,
      precollision health (including jaw pain), collision parameters and collision
      related symptoms, including reduced and/or painful jaw movement and injury
      related neck pain. The authors excluded patients who were hospitalized for more
      than two days and those who sustained injuries as a pedestrian, bicyclist or
      motorcyclist. In determining incidence rates, the authors also excluded those who
      had had jaw pain before the collision. RESULTS: The incidence of reduced and/or
      painful jaw movement was 14.9 percent (n = 1,158), and it was higher in subjects
      with WADs (15.8 percent) than in those without WADs (4.7 percent; relative risk =
      3.36, 95 percent confidence interval, 2.36 to 4.78). Within the WAD injuries,
      multivariable logistic regression revealed that the onset of reduced and/or
      painful jaw movement was associated with female sex; age < 50 years; having hit
      one's head in the collision; and postinjury symptoms of difficulty swallowing,
      ringing in the ears, dizziness or unsteadiness, and more intense neck pain.
      Collision parameters, such as head position at the time of the crash and headrest
      use and type, were not associated with onset of jaw symptoms. CONCLUSIONS:
      Reduced or painful jaw movement was more common in people with WADs than in those
      with other collision-related injuries. Among those with WADs, reduced or painful
      jaw movement was more common in women and younger people. CLINICAL IMPLICATIONS:
      Reduced or painful jaw movement is an important aspect of WADs, and more studies
      are needed to determine how to best assess and treat this problem.

PMID- 17197408
TI  - How do we measure shortages of dental hygienists and dental assistants? Evidence
      from California: 1997-2005.
AB  - BACKGROUND: The authors examined the labor market for registered dental
      hygienists (RDHs) and dental assistants (DAs) in California from 1997 to 2005 to
      determine whether there was a shortage in either market. METHODS: This analysis
      used economic indicators interpreted within an economic framework to investigate
      trends in labor force numbers and market-determined wages for RDHs and DAs.
      Rising inflation-adjusted mean wages indicated a labor shortage, while declining
      inflation-adjusted mean wages indicated a labor surplus. RESULTS: From 1999 to
      2002, the wages for RDHs increased 48 percent and then stabilized, indicating a
      shortage had occurred, after which the market achieved equilibrium. Wages for DAs
      increased 13.9 percent from 1997 to 2001, but then declined from 2001 to 2005,
      indicating a shortage that then became a surplus. The market for DAs may not have
      stabilized. CONCLUSIONS: Wages increased for RDHs and DAs, suggesting that labor
      shortages occurred in both markets. The large supply response in the market for
      DAs resulted in wages declining after their initial rise. PRACTICE IMPLICATIONS:
      Tracking the local labor markets for RDHs and DAs will enable dental
      professionals to respond more efficiently to market signals.

PMID- 17197409
TI  - When is a full-crown restoration indicated?

PMID- 17197410
TI  - The passion for dentistry.

PMID- 17197411
TI  - What are my ethical obligations in enhancing my practice through marketing?

PMID- 17197412
TI  - For the dental patient: infants, formula and fluoride.

PMID- 17197413
TI  - Signatures of strong population differentiation shape extended haplotypes across
      the human CD28, CTLA4, and ICOS costimulatory genes.
AB  - The three members of the costimulatory receptor family, CD28, CTLA-4, and ICOS,
      have complementary effects on T cell activation, and their balance controls the
      overall outcome of immune and autoimmune responses. They are encoded in a short
      genomic interval, and overall activity may result from interplay between allelic
      variants at each locus. With multiethnic DNA panels that represent a wide
      spectrum of human populations, we demonstrate long-range linkage disequilibrium
      among the three genes. A large fraction of the variation found in the locus can
      be explained by the presence of extended haplotypes encompassing variants at
      CD28, CTLA4, and the ICOS promoter. There are unusual differences in the
      distribution of some variants and haplotypes between geographic regions. The
      differences may reflect demographic events and/or the adaptation to diverse
      environmental and microbial challenges encountered in the course of human
      migrations and will be important to consider when interpreting association to
      immune/autoimmune responsiveness.

PMID- 17197415
TI  - Precise physical models of protein-DNA interaction from high-throughput data.
AB  - A cell's ability to regulate gene transcription depends in large part on the
      energy with which transcription factors (TFs) bind their DNA regulatory sites.
      Obtaining accurate models of this binding energy is therefore an important goal
      for quantitative biology. In this article, we present a principled likelihood
      based approach for inferring physical models of TF-DNA binding energy from the
      data produced by modern high-throughput binding assays. Central to our analysis
      is the ability to assess the relative likelihood of different model parameters
      given experimental observations. We take a unique approach to this problem and
      show how to compute likelihood without any explicit assumptions about the noise
      that inevitably corrupts such measurements. Sampling possible choices for model
      parameters according to this likelihood function, we can then make probabilistic
      predictions for the identities of binding sites and their physical binding
      energies. Applying this procedure to previously published data on the
      Saccharomyces cerevisiae TF Abf1p, we find models of TF binding whose parameters
      are determined with remarkable precision. Evidence for the accuracy of these
      models is provided by an astonishing level of phylogenetic conservation in the
      predicted energies of putative binding sites. Results from in vivo and in vitro
      experiments also provide highly consistent characterizations of Abf1p, a result
      that contrasts with a previous analysis of the same data.

PMID- 17197414
TI  - Molecular insights into substrate recognition and catalysis by tryptophan 2,3
      dioxygenase.
AB  - Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) constitute
      an important, yet relatively poorly understood, family of heme-containing
      enzymes. Here, we report extensive structural and biochemical studies of the
      Xanthomonas campestris TDO and a related protein SO4414 from Shewanella
      oneidensis, including the structure at 1.6-A resolution of the catalytically
      active, ferrous form of TDO in a binary complex with the substrate L-Trp. The
      carboxylate and ammonium moieties of tryptophan are recognized by electrostatic
      and hydrogen-bonding interactions with the enzyme and a propionate group of the
      heme, thus defining the L-stereospecificity. A second, possibly allosteric, L-Trp
      binding site is present at the tetramer interface. The sixth coordination site of
      the heme-iron is vacant, providing a dioxygen-binding site that would also
      involve interactions with the ammonium moiety of L-Trp and the amide nitrogen of
      a glycine residue. The indole ring is positioned correctly for oxygenation at the
      C2 and C3 atoms. The active site is fully formed only in the binary complex, and
      biochemical experiments confirm this induced-fit behavior of the enzyme. The
      active site is completely devoid of water during catalysis, which is supported by
      our electrochemical studies showing significant stabilization of the enzyme upon
      substrate binding.

PMID- 17197417
TI  - Cross-talk between singlet oxygen- and hydrogen peroxide-dependent signaling of
      stress responses in Arabidopsis thaliana.
AB  - Upon a dark-to-light shift, the conditional fluorescent (flu) mutant of
      Arabidopsis releases singlet oxygen (1O2) within the plastid compartment.
      Distinct sets of nuclear genes are activated that are different from those
      induced by superoxide (O2*-)) and/or hydrogen peroxide (H2O2), suggesting that
      different types of reactive oxygen species activate distinct signaling pathways.
      It is not known whether the pathways operate separately or interact with each
      other. We have addressed this problem by modulating noninvasively the level of
      H2O2 in plastids by means of a transgenic line that overexpresses the thylakoid
      bound ascorbate peroxidase (tAPX). The overexpression of the H2O2-specific
      scavenger reduced strongly the activation of nuclear genes in plants treated with
      the herbicide paraquat that in the light leads to the enhanced generation of O2*-
      and H2O2. In the flu mutant overexpressing tAPX, the intensity of 1O2-mediated
      cell death and growth inhibition was increased when compared with the flu
      parental line. Also, the expression of most of the nuclear genes that were
      rapidly activated after the release of 1O2 was significantly higher in flu plants
      overexpressing tAPX, whereas in wild-type plants, overexpression of tAPX did not
      lead to visible stress responses and had only a very minor impact on nuclear gene
      expression. The results suggest that H2O2 antagonizes the 1O2-mediated signaling
      of stress responses as seen in the flu mutant. This cross-talk between H2O2- and
      1O2-dependent signaling pathways might contribute to the overall stability and
      robustness of wild-type plants exposed to adverse environmental stress
      conditions.

PMID- 17197416
TI  - Signal transduction pathway of TonB-dependent transporters.
AB  - Transcription of the ferric citrate import system is regulated by ferric citrate
      binding to the outer membrane transporter FecA. A signal indicating transporter
      occupancy is relayed across the outer membrane to energy-transducing and
      regulatory proteins embedded in the cytoplasmic membrane. Because transcriptional
      activation is not coupled to ferric citrate import, an allosteric mechanism
      underlies this complex signaling mechanism. Using evolution-based statistical
      analysis we have identified a sparse but structurally connected network of
      residues that links distant functional sites in FecA. Functional analyses of
      these positions confirm their involvement in the mechanism that regulates
      transcriptional activation in response to ferric citrate binding at the cell
      surface. This mechanism appears to be conserved and provides the structural basis
      for the allosteric signaling of TonB-dependent transporters.

PMID- 17197418
TI  - Ovarian wedge resection restores fertility in estrogen receptor beta knockout
      (ERbeta-/-) mice.
AB  - Ovulation rarely occurs in mice in which the estrogen receptor beta (ERbeta) gene
      has been inactivated (ERbeta-/- mice). Here, we investigated whether this
      subfertility is due to a defect in the ovary itself or to more general endocrine
      changes in ERbeta-/- mice. We transplanted ERbeta-/- ovaries into WT mice and WT
      ovaries into ERbeta-/- mice. Upon mating with ERbeta-/- males, fertility
      increased from 20% in control intact ERbeta-/- group to 40% in the WT recipients
      with ERbeta-/- ovaries. The transplantation procedure was not efficient, and when
      WT ovaries were transplanted into WT mice, fertility was only 36%. Surgical
      ovarian wedge resection, a procedure which induces ovulation in anovulatory women
      with polycystic ovarian syndrome, resulted in 100% fertility of ERbeta-/- mice.
      In ERbeta-/- mice, as the follicles enlarged, the thecal layer remained very
      compact (revealed by H&E and collagen staining), and there was no increase in
      vascularization (measured as smooth muscle actin). In addition, there was an
      increase in PDGF receptor alpha (PDGFRalpha) and a decrease in PDGFbeta
      expression in the granulosa cells, similar to what has been found in follitropin
      receptor knockout mice. After wedge resection, expression of both smooth muscle
      actin and PDGFRs was normalized. During normal follicular development, increased
      vascularization of the thecal layer is a prerequisite for further follicular
      growth. We suggest that the defect in ERbeta-/- mouse ovaries is a failure of
      communication between the granulosa and thecal layers. The follicles do not
      mature because of insufficient blood supply. This problem is overcome by
      stimulating neovascularization by simple wedge resection of the ovaries.

PMID- 17197419
TI  - par genes and the pathology of chromosome loss in Vibrio cholerae.
AB  - The causes and consequences of chromosome loss in bacteria with multiple
      chromosomes are unknown. Vibrio cholerae, the causative agent of the severe
      diarrheal disease cholera, has two circular chromosomes. Like many other
      bacterial chromosomes, both V. cholerae chromosomes contain homologues of plasmid
      partitioning (par) genes. In plasmids, par genes act to segregate plasmid
      molecules to daughter cells and thereby ensure plasmid maintenance; however, the
      contribution of par genes to chromosome segregation is not clear. Here, we show
      that the chromosome II parAB2 genes are essential for the segregation of
      chromosome II but not chromosome I. In a parAB2 deletion mutant, chromosome II is
      mislocalized and frequently fails to segregate, yielding cells with only
      chromosome I. These cells divide once; their progeny are not viable. Instead,
      chromosome II-deficient cells undergo dramatic cell enlargement, nucleoid
      condensation and degradation, and loss of membrane integrity. The highly
      consistent nature of these cytologic changes suggests that prokaryotes, like
      eukaryotes, may possess characteristic death pathways.

PMID- 17197420
TI  - The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function
      pathogenic mechanism.
AB  - Dominantly inherited mutations in the genes encoding presenilins (PS) and the
      amyloid precursor protein (APP) are the major causes of familial Alzheimer's
      disease (AD). The prevailing view of AD pathogenesis posits that accumulation of
      beta-amyloid (Abeta) peptides, particularly Abeta42, is the central event
      triggering neurodegeneration. Emerging evidence, however, suggests that loss of
      essential functions of PS could better explain dementia and neurodegeneration in
      AD. First, conditional inactivation of PS in the adult mouse brain causes
      progressive memory loss and neurodegeneration resembling AD, whereas mouse models
      based on overproduction of Abeta have failed to produce neurodegeneration.
      Second, whereas pathogenic PS mutations enhance Abeta42 production, they
      typically reduce Abeta40 generation and impair other PS-dependent activities.
      Third, gamma-secretase inhibitors can enhance the production of Abeta42 while
      blocking other gamma-secretase activities, thus mimicking the effects of PS
      mutations. Finally, PS mutations have been identified in frontotemporal dementia,
      which lacks amyloid pathology. Based on these and other observations, we propose
      that partial loss of PS function may underlie memory impairment and
      neurodegeneration in the pathogenesis of AD. We also speculate that Abeta42 may
      act primarily to antagonize PS-dependent functions, possibly by operating as an
      active site-directed inhibitor of gamma-secretase.

PMID- 17197421
TI  - Internal conversion to the electronic ground state occurs via two distinct
      pathways for pyrimidine bases in aqueous solution.
AB  - The femtosecond transient absorption technique was used to study the relaxation
      of excited electronic states created by absorption of 267-nm light in all of the
      naturally occurring pyrimidine DNA and RNA bases in aqueous solution. The results
      reveal a surprising bifurcation of the initial excited-state population in <1 ps
      to two nonradiative decay channels within the manifold of singlet states. The
      first is the subpicosecond internal conversion channel first characterized in
      2000. The second channel involves passage through a dark intermediate state
      assigned to a lowest-energy (1)npi* state. Approximately 10-50% of all
      photoexcited pyrimidine bases decay via the (1)npi* state, which has a lifetime
      of 10-150 ps. Three- to 6-fold-longer lifetimes are seen for pyrimidine
      nucleotides and nucleosides than for the corresponding free bases, revealing an
      unprecedented effect of ribosyl substitution on electronic energy relaxation. A
      small fraction of the (1)npi* population is proposed to undergo intersystem
      crossing to the lowest triplet state in competition with vibrational cooling,
      explaining the higher triplet yields observed for pyrimidine versus purine bases
      at room temperature. Some simple correlations exist between yields of the (1)npi*
      state and yields of some pyrimidine photoproducts, but more work is needed before
      the photochemical consequences of this state can be definitively determined.
      These findings lead to a dramatically different picture of electronic energy
      relaxation in single pyrimidine bases with important ramifications for
      understanding DNA photostability.

PMID- 17197422
TI  - Population size and relatedness affect fitness of a self-incompatible invasive
      plant.
AB  - One of the lingering paradoxes in invasion biology is how founder populations of
      an introduced species are able to overcome the limitations of small size and, in
      a "reversal of fortune," proliferate in a new habitat. The transition from
      colonist to invader is especially enigmatic for self-incompatible species, which
      must find a mate to reproduce. In small populations, the inability to find a mate
      can result in the Allee effect, a positive relationship between individual
      fitness and population size or density. Theoretically, the Allee effect should be
      common in founder populations of self-incompatible colonizing species and may
      account for the high rate of failed introductions, but little supporting evidence
      exists. We created a field experiment to test whether the Allee effect affects
      the maternal fitness of a self-incompatible invasive species, wild radish
      (Raphanus sativus). We created populations of varying size and relatedness. We
      measured maternal fitness in terms of both fruit set per flower and seed number
      per fruit. We found that both population size and the level of genetic
      relatedness among individuals influence maternal reproductive success. Our
      results explicitly define an ecological genetic obstacle faced by populations of
      an exotic species on its way to becoming invasive. Such a mechanistic
      understanding of the invasions of species that require a mate can and should be
      exploited for both controlling current outbreaks and reducing their frequency in
      the future.

PMID- 17197423
TI  - The first fossil leaf insect: 47 million years of specialized cryptic morphology
      and behavior.
AB  - Stick and leaf insects (insect order Phasmatodea) are represented primarily by
      twig-imitating slender forms. Only a small percentage ( approximately 1%) of
      extant phasmids belong to the leaf insects (Phylliinae), which exhibit an extreme
      form of morphological and behavioral leaf mimicry. Fossils of phasmid insects are
      extremely rare worldwide. Here we report the first fossil leaf insect, Eophyllium
      messelensis gen. et sp. nov., from 47-million-year-old deposits at Messel in
      Germany. The new specimen, a male, is exquisitely preserved and displays the same
      foliaceous appearance as extant male leaf insects. Clearly, an advanced form of
      extant angiosperm leaf mimicry had already evolved early in the Eocene. We infer
      that this trait was combined with a special behavior, catalepsy or "adaptive
      stillness," enabling Eophyllium to deceive visually oriented predators. Potential
      predators reported from the Eocene are birds, early primates, and bats. The
      combination of primitive and derived characters revealed by Eophyllium allows the
      determination of its exact phylogenetic position and illuminates the evolution of
      leaf mimicry for this insect group. It provides direct evidence that Phylliinae
      originated at least 47 Mya. Eophyllium enlarges the known geographical range of
      Phylliinae, currently restricted to southeast Asia, which is apparently a relict
      distribution. This fossil leaf insect bears considerable resemblance to extant
      individuals in size and cryptic morphology, indicating minimal change in 47
      million years. This absence of evolutionary change is an outstanding example of
      morphological and, probably, behavioral stasis.

PMID- 17197424
TI  - Neutralization of a single arginine residue gates open a two-pore domain, alkali
      activated K+ channel.
AB  - Potassium channels share a common selectivity filter that determines the
      conduction characteristics of the pore. Diversity in K+ channels is given by how
      they are gated open. TASK-2, TALK-1, and TALK-2 are two-pore region (2P) KCNK K+
      channels gated open by extracellular alkalinization. We have explored the
      mechanism for this alkalinization-dependent gating using molecular simulation and
      site-directed mutagenesis followed by functional assay. We show that the side
      chain of a single arginine residue (R224) near the pore senses pH in TASK-2 with
      an unusual pKa of 8.0, a shift likely due to its hydrophobic environment. R224
      would block the channel through an electrostatic effect on the pore, a situation
      relieved by its deprotonation by alkalinization. A lysine residue in TALK-2
      fulfills the same role but with a largely unchanged pKa, which correlates with an
      environment that stabilizes its positive charge. In addition to suggesting
      unified alkaline pH-gating mechanisms within the TALK subfamily of channels, our
      results illustrate in a physiological context the principle that hydrophobic
      environment can drastically modulate the pKa of charged amino acids within a
      protein.

PMID- 17197425
TI  - Contingent Pacific-Atlantic Ocean influence on multicentury wildfire synchrony
      over western North America.
AB  - Widespread synchronous wildfires driven by climatic variation, such as those that
      swept western North America during 1996, 2000, and 2002, can result in major
      environmental and societal impacts. Understanding relationships between
      continental-scale patterns of drought and modes of sea surface temperatures
      (SSTs) such as El Nino-Southern Oscillation (ENSO), Pacific Decadal Oscillation
      (PDO), and Atlantic Multidecadal Oscillation (AMO) may explain how interannual to
      multidecadal variability in SSTs drives fire at continental scales. We used local
      wildfire chronologies reconstructed from fire scars on tree rings across western
      North America and independent reconstructions of SST developed from tree-ring
      widths at other sites to examine the relationships of multicentury patterns of
      climate and fire synchrony. From 33,039 annually resolved fire-scar dates at 238
      sites (the largest paleofire record yet assembled), we examined forest fires at
      regional and subcontinental scales. Since 1550 CE, drought and forest fires
      covaried across the West, but in a manner contingent on SST modes. During certain
      phases of ENSO and PDO, fire was synchronous within broad subregions and
      sometimes asynchronous among those regions. In contrast, fires were most commonly
      synchronous across the West during warm phases of the AMO. ENSO and PDO were the
      main drivers of high-frequency variation in fire (interannual to decadal),
      whereas the AMO conditionally changed the strength and spatial influence of ENSO
      and PDO on wildfire occurrence at multidecadal scales. A current warming trend in
      AMO suggests that we may expect an increase in widespread, synchronous fires
      across the western U.S. in coming decades.

PMID- 17197426
TI  - Alloantigen-enhanced accumulation of CCR5+ 'effector' regulatory T cells in the
      gravid uterus.
AB  - Regulatory T cells play an essential role in preventing fetal rejection by the
      maternal immune system. Here we show that, based on the expression of CCR5,
      regulatory T cells can be divided into a highly suppressive CCR5+ and a far less
      suppressive CCR5- subpopulation, suggesting that the former represent the
      effector arm of regulatory T cells. Although regulatory T cells from CCR5-/- gene
      deletion mutants still suppress, they are less effective mediators of maternal
      fetal tolerance. The accumulation of CCR5+ regulatory T cells at this site
      appears to be enhanced by alloantigen. This finding is in stark contrast to the
      systemic expansion of regulatory T cells during pregnancy, which appears to be
      alloantigen-independent. The fact that CCR5+ regulatory T cells preferentially
      accumulate in the gravid uterus and that expression of CCR5 on regulatory T cells
      can be induced by activation lead us to propose that CCR5 is responsible for the
      accumulation of those regulatory T cells that have been activated by paternal
      antigens.

PMID- 17197427
TI  - MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human
      mesenchymal stem cells: differential regulation by inflammatory cytokines.
AB  - Human mesenchymal stem cells (hMSCs) represent promising tools in various
      clinical applications, including the regeneration of injured tissues by
      endogenous or transplanted hMSCs. The molecular mechanisms, however, that control
      hMSC mobilization and homing which require invasion through extracellular matrix
      (ECM) barriers are almost unknown. We have analyzed bone marrow-derivedhMSCs and
      detected strong expression and synthesis of matrix metalloproteinase 2 (MMP-2),
      membrane type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinase 1 (TIMP-1),
      and TIMP-2. The ability of hMSCs to traverse reconstituted human basement
      membranes was effectively blocked in the presence of synthetic MMP inhibitors.
      Detailed studies by RNA interference revealed that gene knock-down of MMP-2, MT1
      MMP, or TIMP-2 substantially impaired hMSC invasion, whereas silencing of TIMP-1
      enhanced cell migration, indicating opposing roles of both TIMPs in this process.
      Moreover, the inflammatory cytokines TGF-beta1, IL-1beta, and TNF-alpha up
      regulated MMP-2, MT1-MMP, and/or MMP-9 production in these cells, resulting in a
      strong stimulation of chemotactic migration through ECM, whereas the chemokine
      SDF-1alpha exhibited minor effects on MMP/TIMP expression and cell invasion.
      Thus, induction of specific MMP activity in hMSCs by inflammatory cytokines
      promotes directed cell migration across reconstituted basement membranes in vitro
      providing a potential mechanism in hMSC recruitment and extravasation into
      injured tissues in vivo.

PMID- 17197429
TI  - Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron
      deficiency-mediated growth suppression.
AB  - Iron (Fe) plays an important role in proliferation, and Fe deficiency results in
      G(1)/S arrest. Despite this, the precise role of Fe in cell-cycle control remains
      unclear. Cyclin D1 plays a critical function in G(1) progression by interacting
      with cyclin-dependent kinases. Previously, we examined the effect of Fe depletion
      on the expression of cell-cycle control molecules and identified a marked
      decrease in cyclin D1 protein, although the mechanism involved was unknown. In
      this study, we showed that cyclin D1 was regulated posttranscriptionally by Fe
      depletion. Iron chelation of cells in culture using desferrioxamine (DFO) or 2
      hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) decreased cyclin D1
      protein levels after 14 hours and was rescued by the addition of Fe. Cyclin D1
      half-life in control cells was 80 +/- 15 minutes (n = 5), while in chelator
      treated cells it was significantly (P < .008) decreased to 38 +/- 3 minutes (n =
      5). Proteasomal inhibitors rescued the Fe chelator-mediated decrease in cyclin D1
      protein, suggesting the role of the proteasome. In Fe-replete cells, cyclin D1
      was degraded in an ubiquitin-dependent manner, while Fe depletion induced a
      ubiquitin-independent pathway. This is the first report linking Fe depletion
      mediated growth suppression at G(1)/S to a mechanism inducing cyclin D1
      proteolysis.

PMID- 17197428
TI  - New differentiation pathway for double-negative regulatory T cells that regulates
      the magnitude of immune responses.
AB  - Recent studies have demonstrated that in peripheral lymphoid tissues of normal
      mice and healthy humans, 1% to 5% of alphabeta T-cell receptor-positive (TCR(+))
      T cells are CD4(-)CD8(-) (double-negative [DN]) T cells, capable of down
      regulating immune responses. However, the origin and developmental pathway of DN
      T cells is still not clear. In this study, by monitoring CD4 expression during T
      cell proliferation and differentiation, we identified a new differentiation
      pathway for the conversion of CD4(+) T cells to DN regulatory T cells. We showed
      that the converted DN T cells retained a stable phenotype after restimulation and
      that furthermore, the disappearance of cell-surface CD4 molecules on converted DN
      T cells was a result of CD4 gene silencing. The converted DN T cells were
      resistant to activation-induced cell death (AICD) and expressed a unique set of
      cell-surface markers and gene profiles. These cells were highly potent in
      suppressing alloimmune responses both in vitro and in vivo in an antigen-specific
      manner. Perforin was highly expressed by the converted DN regulatory T cells and
      played a role in DN T-cell-mediated suppression. Our findings thus identify a new
      differentiation pathway for DN regulatory T cells and uncover a new intrinsic
      homeostatic mechanism that regulates the magnitude of immune responses. This
      pathway provides a novel, cell-based, therapeutic approach for preventing
      allograft rejection.

PMID- 17197430
TI  - Mast cell-derived TNF can promote Th17 cell-dependent neutrophil recruitment in
      ovalbumin-challenged OTII mice.
AB  - Both mast cells and IL-17 can contribute to host defense and pathology in part by
      orchestrating neutrophil recruitment, but the possible role of mast cells in IL
      17-induced inflammation remains to be defined. We found that mast cells and IL
      17, but neither IFN-gamma nor FcRgamma signaling, contributed significantly to
      the antigen (Ag)-dependent airway neutrophilia elicited in ovalbumin-specific T
      cell receptor (TCR)-expressing C57BL/6-OTII mice, and that IFN-gamma
      significantly suppressed IL-17-dependent airway neutrophilia in this setting. IL
      18, IL-1beta, and TNF each contributed significantly to the development of Ag-
      and T helper 17 (Th17 cell)-mediated airway neutrophilia. Moreover, IL-17
      enhanced mast cell TNF production in vitro, and mast cell-associated TNF
      contributed significantly to Ag- and Th17 cell-mediated airway neutrophilia in
      vivo. By contrast, we detected no significant role for the candidate mediators
      histamine, PGD(2), LTB(4), CXCL10, or IL-16, each of which can be produced by
      mast cells and other cell types, in the neutrophil infiltration elicited in this
      model. These findings establish that mast cells and mast cell-derived TNF can
      significantly enhance, by FcRgamma-independent mechanisms, the Ag- and Th17 cell
      dependent development of a neutrophil-rich inflammatory response at a site of Ag
      challenge.

PMID- 17197431
TI  - A leukemia fusion protein attenuates the spindle checkpoint and promotes
      aneuploidy.
AB  - The 8;21 chromosomal translocation occurs in 15% to 40% of patients with the FAB
      M2 subtype of acute myeloid leukemia (AML). This chromosomal abnormality fuses
      part of the AML1/RUNX1 gene to the ETO/MTG8 gene and generates the AML1-ETO
      protein. We previously identified a C-terminal truncated AML1-ETO protein (AEtr)
      in a mouse leukemia model. AEtr is almost identical to the AML1-ETO exon 9a
      isoform expressed in leukemia patients. Here, we describe a novel function of
      AEtr in the development of aneuploidy through spindle checkpoint attenuation.
      AEtr cells had a reduced mitotic index following nocodazole treatment, suggesting
      a failure in a subset of cells to arrest in mitosis with a functional spindle
      checkpoint. Additionally, primary leukemia cells and cell lines expressing AEtr
      were aneuploid. Moreover, AEtr cells had reduced levels of several spindle
      checkpoint proteins including BubR1 and securin following treatment with the
      spindle poison nocodazole. These results suggest that inactivation of the spindle
      checkpoint may contribute to the development of aneuploidy described in t(8;21)
      leukemia patients.

PMID- 17197432
TI  - Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen
      platelet responses via the alpha2beta1-integrin receptor.
AB  - Endorepellin, a C-terminal fragment of the vascular basement membrane
      proteoglycan perlecan, inhibits angiogenesis via the alpha2beta1-integrin
      receptor. Because this integrin is also implicated in platelet-collagen responses
      and because endorepellin or its fragments are generated in response to injury and
      inflammation, we hypothesized that endorepellin could also affect platelet
      biology. We discovered that endorepellin supported alpha2beta1-dependent platelet
      adhesion, without appreciably activating or aggregating platelets. Notably,
      endorepellin enhanced collagen-evoked responses in platelets, in a src kinase
      dependent fashion, and enhanced the collagen-inhibitory effect of an alpha2beta1
      integrin function-blocking antibody. Collectively, these results suggest that
      endorepellin/alpha2beta1-integrin interaction and effects are specific and
      dependent on cell type, differ from those emanated by exposure to collagen, and
      may be due to cellular differences in alpha2beta1-integrin activation/ligand
      affinity state. These studies also suggest a heretofore unrecognized role for
      angiostatic basement membrane fragments in platelet biology.

PMID- 17197434
TI  - MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by
      aberrant somatic hypermutation.
AB  - Recently, a novel mechanism introducing genetic instability, termed aberrant
      somatic hypermutation (ASHM), has been described in diffuse large B-cell
      lymphoma. To further investigate whether ASHM also occurs in mucosa-associated
      lymphoid tissue type (MALT) lymphoma, we studied the mutation profile of PIM1,
      PAX5, RhoH/TTF, and c-MYC in 17 MALT lymphomas and 17 extranodal diffuse large B
      cell lymphomas (DLBCLs) still exhibiting a low-grade MALT lymphoma component
      (transformed MALT lymphoma). Mutations in one or more genes were detected in 13
      (76.5%) of 17 cases of MALT lymphomas and in all of 17 (100%) cases of extranodal
      DLBCL. A total of 100 sequence variants were found in 30 of 34 cases, 28 in the
      MALT lymphomas and 72 in extranodal DLBCL. Further, in PIM1 and c-MYC some of the
      mutations were found to affect coding exons, leading to amino acid exchanges,
      thus potentially altering gene function. Expression levels of activation-induced
      cytidine deaminase (AID), an enzyme essential for somatic hypermutation (SHM),
      was associated with the mutational load. These data indicate that aberrant SHM is
      associated with extranodal DLBCL and MALT lymphoma, likewise. By mutating
      regulatory and coding sequences of the targeted genes, ASHM may represent a major
      contributor to their pathogenesis.

PMID- 17197433
TI  - Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion
      protein and shows potent antitumor activity with low adverse effects on t(8;21)
      leukemia in vitro and in vivo.
AB  - Studies have documented the potential antitumor activities of oridonin, a
      compound extracted from medicinal herbs. However, whether oridonin can be used in
      the selected setting of hematology/oncology remains obscure. Here, we reported
      that oridonin induced apoptosis of t(8;21) acute myeloid leukemic (AML) cells.
      Intriguingly, the t(8;21) product AML1-ETO (AE) fusion protein, which plays a
      critical role in leukemogenesis, was degraded with generation of a catabolic
      fragment, while the expression pattern of AE target genes investigated could be
      reprogrammed. The ectopic expression of AE enhanced the apoptotic effect of
      oridonin in U937 cells. Preincubation with caspase inhibitors blocked oridonin
      triggered cleavage of AE, while substitution of Ala for Asp at residues 188 in
      ETO moiety of the fusion abrogated AE degradation. Furthermore, oridonin
      prolonged lifespan of C57 mice bearing truncated AE-expressing leukemic cells
      without suppression of bone marrow or reduction of body weight of animals, and
      exerted synergic effects while combined with cytosine arabinoside. Oridonin also
      inhibited tumor growth in nude mice inoculated with t(8;21)-harboring Kasumi-1
      cells. These results suggest that oridonin may be a potential antileukemia agent
      that targets AE oncoprotein at residue D188 with low adverse effect, and may be
      helpful for the treatment of patients with t(8;21) AML.

PMID- 17197436
TI  - Trapping and apoptosis of novel subsets of memory T lymphocytes expressing CCR6
      in the spleen of HIV-infected patients.
AB  - CCR6, a homeostatic chemokine receptor, is shown here to characterize subsets of
      both central and effector memory T cells that secrete high levels of IL-2 and TNF
      alpha in response to polyclonal and antigen-specific stimulation. CCR6(+) T
      lymphocytes disappeared dramatically from the peripheral blood of HIV-infected
      patients as HIV disease progressed. The capacity of CD4(+)CCR6(+) to secrete
      multiple cytokines remained intact among HIV-infected long-term nonprogressors
      but was partially lost from subjects with standard disease progression. CCR6(+) T
      lymphocytes, regardless of their CCR7 expression, accumulated in the spleen of
      HIV-infected patients, where they died by apoptosis. Assessment of CCR6
      expression allowed us to describe novel memory T-cell subpopulations capable of
      high cytokine production and provided evidence of a pathologic CCR6-dependent
      pathway of memory T-cell homing that may participate in the loss of memory
      response against infections.

PMID- 17197435
TI  - Polymorphisms in DNA repair genes and therapeutic outcomes of AML patients from
      SWOG clinical trials.
AB  - Repair of damage to DNA resulting from chemotherapy may influence drug toxicity
      and survival in response to treatment. We evaluated the role of polymorphisms in
      DNA repair genes APE1, XRCC1, ERCC1, XPD, and XRCC3 in predicting therapeutic
      outcomes of older adults with acute myeloid leukemia (AML) from 2 Southwest
      Oncology Group (SWOG) clinical trials. All patients received standard
      chemotherapy induction regimens. Using logistic and proportional hazards
      regression models, relationships between genotypes, haplotypes, and toxicities,
      response to induction therapy, and overall survival were evaluated. Patients with
      XPD Gln751C/Asp312G ('D') haplotype were more likely to have complete response
      (OR = 3.06; 95% CI, 1.44-6.70) and less likely to have resistant disease (OR =
      0.32; 95%CI, 0.14-0.72) than patients with other haplotypes. ERCC1 polymorphisms
      were significantly associated with lung (P = .037) and metabolic (P = .041)
      toxicities, and patients with the XRCC3 241Met variant had reduced risk of liver
      toxicity (OR = 0.32; 95%CI, 0.11-0.95). Significant associations with other
      toxicities were also found for variant XPD genotypes/haplotypes. These data from
      clinical trials of older patients treated for AML indicate that variants in DNA
      repair pathways may have an impact on both outcomes of patients and toxicities
      associated with treatments. With validation of results in larger samples, these
      findings could lead to optimizing individual chemotherapy options.

PMID- 17197437
TI  - Biochemical characterization of a regulatory cascade controlling transcription of
      the Pseudomonas aeruginosa type III secretion system.
AB  - Many Gram-negative pathogens utilize type III secretion systems (T3SS) to
      translocate effector proteins into eukaryotic host cells. Expression of T3SS
      genes is highly regulated and is often coupled to type III secretory activity.
      Transcription of the Pseudomonas aeruginosa T3SS genes is coupled to secretion by
      a cascade of interacting regulatory proteins (ExsA, ExsD, ExsC, and ExsE). ExsA
      is an activator of type III gene transcription, ExsD binds ExsA to inhibit
      transcription, ExsC inhibits ExsD activity, and ExsE inhibits ExsC activity. The
      entire process is coupled to secretion by virtue of the fact that ExsE is a
      secreted substrate of the T3SS. Changes in the intracellular concentration of
      ExsE are thought to govern formation of the ExsC-ExsE, ExsC-ExsD, and ExsD-ExsA
      complexes. Whereas formation of the ExsC-ExsE complex allows ExsD to bind ExsA
      and transcription of the T3SS is repressed, formation of the ExsC-ExsD complex
      sequesters ExsD from ExsA and transcription of the T3SS is induced. In this
      study, we characterized the self-association states of ExsC, ExsD, and ExsE and
      the binding interactions of ExsC with ExsE and ExsD. ExsC exists as a homodimer
      and binds one molecule of ExsE substrate. Dimeric ExsC also interacts directly
      with ExsD to form a heterotetrameric complex. The difference in binding
      affinities between the ExsC-ExsE (K(d) 1 nm) and ExsC-ExsD (K(d) 18 nm) complexes
      supports a model in which ExsC preferentially binds cytoplasmic ExsE, resulting
      in the inhibition of T3SS gene transcription.

PMID- 17197438
TI  - The N-terminal membrane occupation and recognition nexus domain of Arabidopsis
      phosphatidylinositol phosphate kinase 1 regulates enzyme activity.
AB  - The type I B family of phosphatidylinositol phosphate kinases (PIPKs) contain a
      characteristic region of Membrane Occupation and Recognition Nexus (MORN) motifs
      at the N terminus. These MORN motifs are not found in PIPKs from other
      eukaryotes. To understand the impact of the additional N-terminal domain on
      protein function and subcellular distribution, we expressed truncated and full
      length versions of AtPIPK1, one member of this family of PIPKs, in Escherichia
      coli and in tobacco cells grown in suspension culture. Deletion of the N-terminal
      MORN domain (amino acids 1-251) of AtPIPK1 increased the specific activity of the
      remaining C-terminal peptide (DeltaMORN) >4-fold and eliminated activation by
      phosphatidic acid (PtdOH). PtdOH activation could also be eliminated by mutating
      Pro(396) to Ala (P396A) in the predicted linker region between the MORN and the
      kinase homology domains. AtPIPK1 is product-activated and the MORN domain binds
      PtdIns(4,5)P(2). Adding back the MORN peptide to DeltaMORN or to the PtdOH
      activated full-length protein increased activity approximately 2-fold.
      Furthermore, expressing the MORN domain in vivo increased the plasma membrane
      PtdInsP kinase activity. When cells were exposed to hyperosmotic stress, the MORN
      peptide redistributed from the plasma membrane to a lower phase or endomembrane
      fraction. In addition, endogenous PtdInsP kinase activity increased in the
      endomembrane fraction of hyperosmotically stressed cells. We conclude that the
      MORN peptide can regulate both the function and distribution of the enzyme in a
      manner that is sensitive to the lipid environment.

PMID- 17197439
TI  - Hypomagnesemia with secondary hypocalcemia due to a missense mutation in the
      putative pore-forming region of TRPM6.
AB  - Hypomagnesemia with secondary hypocalcemia is an autosomal recessive disorder
      caused by mutations in the TRPM6 gene. Current experimental evidence suggests
      that TRPM6 may function in a specific association with TRPM7 by means of
      heterooligomeric channel complex formation. Here, we report the identification
      and functional characterization of a new hypomagnesemia with secondary
      hypocalcemia missense mutation in TRPM6. The affected subject presented with
      profound hypomagnesemia and hypocalcemia caused by compound heterozygous mutation
      in the TRPM6 gene: 1208(-1)G > A affecting the acceptor splice site preceding
      exon 11, and 3050C > G resulting in the amino acid change (P1017R) in the
      putative pore-forming region of TRPM6. To assess the functional consequences of
      the P1017R mutation, TRPM6(P1017R) and wild-type TRPM6 were co-expressed with
      TRPM7 in Xenopus oocytes and HEK 293 cells, and currents were assessed by two
      electrode voltage clamp and whole cell patch clamp measurements, respectively. Co
      expression of wild-type TRPM6 and TRPM7 resulted in a significant increase in the
      amplitude of TRPM7-like currents. In contrast, TRPM6(P1017R) suppressed TRPM7
      channel activity. In line with these observations, TRPM7, containing the
      corresponding mutation P1040R, displayed a dominant-negative effect upon co
      expression with wild-type TRPM7. Confocal microscopy and fluorescence resonance
      energy transfer recordings demonstrated that the P1017R mutation neither affects
      assembly of TRPM6 with TRPM7, nor co-trafficking of heteromultimeric channel
      complexes to the cell surface. We conclude that a functional defect in the
      putative pore of TRPM6/7 channel complexes is sufficient to impair body magnesium
      homeostasis.

PMID- 17197440
TI  - A novel regulator of telomerase. S100A8 mediates differentiation-dependent and
      calcium-induced inhibition of telomerase activity in the human epidermal
      keratinocyte line HaCaT.
AB  - Recently we reported a differentiation-dependent inhibition of telomerase
      activity in human epidermis. Consistent with this observation we found that in
      keratinocyte cultures calcium-induced differentiation correlates with a decline
      in telomerase activity. To get further support for a role of calcium in the
      regulation of telomerase and to elucidate the underlying molecular mechanisms we
      investigated the effect of calcium on telomerase in the human epidermal
      keratinocyte line HaCaT. Treatment with thapsigargin, which increases
      intracellular calcium concentrations, inhibited telomerase activity without down
      regulating the expression of hTERT (human telomerase reverse transcriptase). This
      observation together with the fact that increasing calcium reduced telomerase
      activity in cell-free extracts suggests that calcium directly interacts with the
      telomerase complex. This interaction could be mediated by the calcium-binding
      protein S100A8 as indicated by its ability to mimic the inhibitory effect of
      calcium. S100A8-induced reduction in telomerase activity was abrogated by S100A9.
      The ratio of both proteins remained constant in cells treated with thapsigargin,
      but their interactions were altered similarly in intact cells after thapsigargin
      treatment and in cell-free extracts in response to calcium. We hypothesize that
      calcium binds to S100A8/S100A9 complexes and alters their composition, thus
      enabling S100A8 to interact with the telomerase complex and inhibit its activity.

PMID- 17197441
TI  - Blockade of class IA phosphoinositide 3-kinase in neutrophils prevents NADPH
      oxidase activation- and adhesion-dependent inflammation.
AB  - We examined the role of class IA phosphoinositide 3-kinase (PI3K) in the
      regulation of activation of NADPH oxidase in PMNs and the mechanism of PMN
      dependent lung inflammation and microvessel injury induced by the pro
      inflammatory cytokine TNF-alpha. TNF-alpha stimulation of PMNs resulted in
      superoxide production that was dependent on CD11b/CD18-mediated PMN adhesion.
      Additionally, TNF-alpha induced the association of CD11b/CD18 with the NADPH
      oxidase subunit Nox2 (gp91(phox)) and phosphorylation of p47(phox), indicating
      the CD11b/CD18 dependence of NADPH oxidase activation. Transduction of wild-type
      PMNs with Deltap85 protein, a dominant-negative form of the class IA PI3K
      regulatory subunit, p85alpha, fused to HIV-TAT (TAT-Deltap85) prevented (i)
      CD11b/CD18-dependent PMN adhesion, (ii) interaction of CD11b/CD18 with Nox2 and
      phosphorylation of p47(phox), and (iii) PMN oxidant production. Furthermore,
      studies in mice showed that i.v. infusion of TAT-Deltap85 significantly reduced
      the recruitment of PMNs in lungs and increase in lung microvascular permeability
      induced by TNF-alpha. We conclude that class IA PI3K serves as a nodal point
      regulating CD11b/CD18-integrin-dependent PMN adhesion and activation of NADPH
      oxidase, and leads to oxidant production at sites of PMN adhesion, and the
      resultant lung microvascular injury in mice.

PMID- 17197442
TI  - Specific role of the truncated betaIV-spectrin Sigma6 in sodium channel
      clustering at axon initial segments and nodes of ranvier.
AB  - At axon initial segments and nodes of Ranvier in neurons, the spectrin membrane
      skeleton plays roles in physically stabilizing the plasma membrane integrity and
      in clustering voltage-gated sodium channels for proper conduction of the action
      potential. betaIV-Spectrin, an essential component of the membrane skeleton at
      these sites, has an N-terminal-truncated isoform, Sigma6, which is expressed at
      much higher levels than the full-length isoform Sigma1. To investigate the role
      of betaIV-spectrin Sigma6, we generated Sigma1-deficient mice with a normal level
      of Sigma6 expression (Sigma1(-/-) mice), and compared their phenotypes with those
      of previously generated mice lacking both Sigma1 and Sigma6(Sigma1Sigma6(-/-)
      mice). The gross neurological defects observed in Sigma1Sigma6(-/-) mice, such as
      hindleg contraction, were apparently ameliorated in Sigma1(-/-) mice. At cellular
      levels, Sigma1Sigma6(-/-) and Sigma1(-/-) neurons similarly exhibited waving and
      swelling of the plasma membrane at axon initial segments and nodes of Ranvier. By
      contrast, the levels of ankyrin G and voltage-gated sodium channels at these
      sites, which are significantly reduced in Sigma1Sigma6(-/-) mice, were
      substantially recovered in Sigma1(-/-) mice. We conclude that the truncated
      betaIV-spectrin isoform Sigma6 plays a specific role in clustering voltage-gated
      sodium channels, whereas it is dispensable for membrane stabilization at axon
      initial segments and nodes of Ranvier.

PMID- 17197443
TI  - Tissue-specific changes in the hydroxylysine content and cross-links of collagens
      and alterations in fibril morphology in lysyl hydroxylase 1 knock-out mice.
AB  - We have generated mice with targeted inactivation of the Plod1 gene for lysyl
      hydroxylase 1 (LH1). Its human mutations cause Ehlers-Danlos syndrome VIA (EDS
      VIA) characterized by muscular hypotonia, joint laxity, and kyphoscoliosis. The
      Plod1(-/-) mice are flaccid and have gait abnormalities. About 15% of them died
      because of aortic rupture and smooth muscle cells in non-ruptured Plod1(-/-)
      aortas showed degenerative changes. Collagen fibrils in the Plod1(-/-) aorta and
      skin had an abnormal morphology. The LH activity level in the Plod1(-/-) skin and
      aorta samples was 35-45% of that in the wild type. The hydroxylysine content was
      decreased in all the Plod1(-/-) tissues, ranging from 22% of that in the wild
      type in the skin to 75 and 86% in the femur and lung. The
      hydroxylysylpyridinoline crosslinks likewise showed decreases in all the Plod1(-/
      ) tissues, ranging from 28 and 33% of that in the wild type in the aorta and
      cornea to 47 and 59% in femur and tendon, while lysylpyridinolines were
      increased. The hydroxylysines found in the Plod1(-/-) collagens and their cross
      links were evidently synthesized by the other two LH isoenzymes. Few data are
      available on abnormalities in EDS VIA tissues other than the skin. Plod1(-/-)
      mice offer an in vivo model for systematic analysis of the tissue-specific
      consequences of the lack of LH1 activity and may also provide a tool for
      analyzing the roles of connective tissue in muscle function and the complex
      interactions occurring in the proper assembly of the extracellular matrix.

PMID- 17197444
TI  - Post-translational arginylation of calreticulin: a new isospecies of calreticulin
      component of stress granules.
AB  - Post-translational arginylation consists of the covalent union of an arginine
      residue to a Glu, Asp, or Cys amino acid at the N-terminal position of proteins.
      This reaction is catalyzed by the enzyme arginyl-tRNA protein transferase. Using
      mass spectrometry, we have recently demonstrated in vitro the post-translational
      incorporation of arginine into the calcium-binding protein calreticulin (CRT). To
      further study arginylated CRT we raised an antibody against the peptide
      (RDPAIYFK) that contains an arginine followed by the first 7 N-terminal amino
      acids of mature rat CRT. This antibody specifically recognizes CRT obtained from
      rat soluble fraction that was arginylated in vitro and also recognizes endogenous
      arginylated CRT from NIH 3T3 cells in culture, indicating that CRT arginylation
      takes place in living cells. Using this antibody we found that arginylation of
      CRT is Ca2+-regulated. In vitro and in NIH 3T3 cells in culture, the level of
      arginylated CRT increased with the addition of a Ca2+ chelator to the medium,
      whereas a decreased arginine incorporation into CRT was found in the presence of
      Ca2+. The arginylated CRT was observed in the cytosol, in contrast to the non
      arginylated CRT that is in the endoplasmic reticulum. Under stress conditions,
      arginylated CRT was found associated to stress granules. These results suggest
      that CRT arginylation occurs in the cytosolic pool of mature CRT (defined by an
      Asp acid N-terminal) that is probably retrotranslocated from the endoplasmic
      reticulum.

PMID- 17197445
TI  - Galphaq-TRPC6-mediated Ca2+ entry induces RhoA activation and resultant
      endothelial cell shape change in response to thrombin.
AB  - RhoA activation and increased intracellular Ca(2+) concentration mediated by the
      activation of transient receptor potential channels (TRPC) both contribute to the
      thrombin-induced increase in endothelial cell contraction, cell shape change, and
      consequently to the mechanism of increased endothelial permeability. Herein, we
      addressed the possibility that TRPC signals RhoA activation and thereby
      contributes in actinomyosin-mediated endothelial cell contraction and increased
      endothelial permeability. Transduction of a constitutively active Galphaq mutant
      in human pulmonary arterial endothelial cells induced RhoA activity. Preventing
      the increase in intracellular Ca2+ concentration by the inhibitor of Galphaq or
      phospholipase C and the Ca2+ chelator, BAPTA-AM, abrogated thrombin-induced RhoA
      activation. Depletion of extracellular Ca2+ also inhibited RhoA activation,
      indicating the requirement of Ca2+ entry in the response. RhoA activation could
      not be ascribed to storeoperated Ca2+ (SOC) entry because SOC entry induced with
      thapsigargin or small interfering RNA-mediated inhibition of TRPC1 expression,
      the predominant SOC channel in these endothelial cells, failed to alter RhoA
      activity. However, activation of receptor-operated Ca2+ entry by oleoyl-2-acetyl
      sn-glycerol, the membrane permeable analogue of the Galphaq-phospholipase C
      product diacylglycerol, induced RhoA activity. Receptor-operated Ca2+ activation
      was mediated by TRPC6 because small interfering RNA-induced TRPC6 knockdown
      significantly reduced Ca2+ entry. TRPC6 knockdown also prevented RhoA activation,
      myosin light chain phosphorylation, and actin stress fiber formation as well as
      inter-endothelial junctional gap formation in response to either oleoyl-2-acetyl
      sn-glycerol or thrombin. TRPC6-mediated RhoA activity was shown to be dependent
      on PKCalpha activation. Our results demonstrate that Galphaq activation of TRPC6
      signals the activation of PKCalpha, and thereby induces RhoA activity and
      endothelial cell contraction.

PMID- 17197446
TI  - Unique ability of activated CD4+ T cells but not rested effectors to migrate to
      non-lymphoid sites in the absence of inflammation.
AB  - Recent studies suggest that effector T cells generated by immune responses
      migrate to multiple non-lymphoid sites, even those without apparent expression of
      antigen or inflammation. To investigate the ability of distinct CD4(+) T
      lymphocyte subsets to enter and persist in non-lymphoid, noninflamed
      compartments, we examined the migration and persistence of naive, effector, and
      rested effector CD4(+) T cells generated in vitro following transfer to
      nonimmunized adoptive hosts. Th1 and Th2 effectors migrated to both lymphoid and
      non-lymphoid organs (peritoneum, fat pads, and lung). In contrast, rested
      effectors and naive cells migrated only to lymphoid areas. Adhesion molecule
      expression, but not chemokine receptor expression, correlated with the ability to
      enter non-lymphoid sites. Donor cells persisted longer in lymphoid than in non
      lymphoid sites. When hosts with naive and memory donor cells were challenged with
      antigen, effectors developed in situ, which also migrated to non-lymphoid sites.
      Memory cells showed an accelerated shift to non-lymphoid migration, in keeping
      with memory effector formation. These results suggest that only recently
      activated effector T cells can disperse to non-lymphoid sites in the absence of
      antigen and inflammation, and as effectors return to rest, they lose this
      ability. These data also argue that memory cells in lymphoid sites are longer
      lived and not in equilibrium with those in non-lymphoid sites.

PMID- 17197447
TI  - Murine CXCR1 is a functional receptor for GCP-2/CXCL6 and interleukin-8/CXCL8.
AB  - Functional interleuin-8 (IL-8) receptors (IL-8RA and IL-8RB: CXCR1 and CXCR2,
      respectively) have been described in human, monkey, dog, rabbit, and guinea pig.
      Although three IL-8R homologues have been found in rat, only one of these, rat
      CXCR2, appears to be functional based on responsiveness to ligands. Similarly,
      CXC chemokines induce biological responses through the murine homolog of CXCR2,
      but the identification of functional rodent CXCR1 homologues has remained
      elusive. We have identified and characterized the mouse CXCR1 homologue (mCXCR1).
      Murine CXCR1 shares 68 and 88% amino acid identity with its human and rat
      counterparts, respectively. Similar to the tissue distribution pattern of rat
      CXCR1, we found murine CXCR1 mRNA expression predominantly in lung, stomach, bone
      marrow, and leukocyte-rich tissues. In contrast to previous reports, we
      determined that mCXCR1 is a functional receptor. We show predominant engagement
      of this receptor by mouse GCP-2/CXCL6, human GCP-2, and IL-8/CXCL8 by binding,
      stimulation of GTPgammaS exchange, and chemotaxis of mCXCR1-transfected cells.
      Furthermore, murine CXCR1 is not responsive to the human CXCR2 ligands ENA
      78/CXCL5, NAP-2/CXCL7, GRO-alpha, -beta, -gamma/CXCL1-3, or rat CINC-1-3. In
      addition, we show concomitant elevation of mCXCR1 and its proposed major ligand,
      GCP-2, positively correlated with paw swelling in murine collagen-induced
      arthritis. This report represents the first description of a functional CXCR1
      like receptor in rodents.

PMID- 17197448
TI  - Human follicular lymphoma cells contain oligomannose glycans in the antigen
      binding site of the B-cell receptor.
AB  - Expression of surface immunoglobulin appears critical for the growth and survival
      of B-cell lymphomas. In follicular lymphoma, we found previously that the Ig
      variable (V) regions in the B-cell receptor express a strikingly high incidence
      of N-glycosylation sequons, NX(S/T). These potential glycosylation sites are
      introduced by somatic mutation and are lymphoma-specific, pointing to their
      involvement in tumor pathogenesis. Analysis of the V region sugars from lymphoma
      derived IgG/IgM reveals that they are mostly oligomannose and, remarkably, are
      located in the antigen-binding site, possibly precluding conventional antigen
      binding. The Fc region contains complex glycans, confirming that the normal
      glycan processing pathway is intact. Binding studies indicate that the
      oligomannose glycans occupying the V regions are accessible to mannose-binding
      lectin. These findings suggest a potential contribution to lymphoma pathogenesis
      involving antigen-independent interaction of surface immunoglobulin of the B-cell
      receptor with mannose-binding molecules of innate immunity in the germinal
      center.

PMID- 17197449
TI  - Direct assessment of CXCR4 mutant conformations reveals complex link between
      receptor structure and G(alpha)(i) activation.
AB  - Ligand binding to G protein-coupled receptors (GPCRs) is thought to induce
      changes in receptor conformation that translate into activation of downstream
      effectors. The link between receptor conformation and activity is still
      insufficiently understood, as current models of GPCR activation fail to take an
      increasing amount of experimental data into account. To elucidate structure
      function relationships in GPCR activation, we used bioluminescence resonance
      energy transfer to directly assess the conformation of mutants of the chemokine
      receptor CXCR4. We analyzed substitutions in the arginine cage DRY motif and in
      the conserved asparagine N(3.35)119, which are pivotal molecular switches for
      receptor conformation and activation. G(alpha)(i) activation of the mutants was
      either similar to wild-type CXCR4 (D133N, Y135A, and N119D) or resulted in loss
      of activity (R134A and N119K). Mutant N119S was constitutively active but further
      activated by agonist. Bioluminescence resonance energy transfer analysis
      suggested no simple correlation between conformational changes in response to
      ligand binding and activation of G(alpha)(i) by the mutants. Different
      conformations of active receptors were detected (for wild-type CXCR4, D133N, and
      N119S), suggesting that different receptor conformations are able to trigger
      G(alpha)(i) activity. Several conformations were also found for inactive mutants.
      These data provide biophysical evidence for different receptor conformations
      being active with respect to a single readout. They support models of GPCR
      structure-activity relationships that take this conformational flexibility of
      active receptors into account.

PMID- 17197451
TI  - Visual diagnosis: a child who has a worsening rash.

PMID- 17197453
TI  - Changing the American diet.

PMID- 17197450
TI  - Modulation of the pancreatic islet beta-cell-delayed rectifier potassium channel
      Kv2.1 by the polyunsaturated fatty acid arachidonate.
AB  - Glucose stimulates both insulin secretion and hydrolysis of arachidonic acid (AA)
      esterified in membrane phospholipids of pancreatic islet beta-cells, and these
      processes are amplified by muscarinic agonists. Here we demonstrate that
      nonesterified AA regulates the biophysical activity of the pancreatic islet beta
      cell-delayed rectifier channel, Kv2.1. Recordings of Kv2.1 currents from INS-1
      insulinoma cells incubated with AA (5 mum) and subjected to graded degrees of
      depolarization exhibit a significantly shorter time-to-peak current interval than
      do control cells. AA causes a rapid decay and reduced peak conductance of delayed
      rectifier currents from INS-1 cells and from primary beta-cells isolated from
      mouse, rat, and human pancreatic islets. Stimulating mouse islets with AA results
      in a significant increase in the frequency of glucose-induced [Ca(2+)]
      oscillations, which is an expected effect of Kv2.1 channel blockade. Stimulation
      with concentrations of glucose and carbachol that accelerate hydrolysis of
      endogenous AA from islet phosphoplipids also results in accelerated Kv2.1
      inactivation and a shorter time-to-peak current interval. Group VIA phospholipase
      A(2) (iPLA(2)beta) hydrolyzes beta-cell membrane phospholipids to release
      nonesterified fatty acids, including AA, and inhibiting iPLA(2)beta prevents the
      muscarinic agonist-induced accelerated Kv2.1 inactivation. Furthermore, glucose
      and carbachol do not significantly affect Kv2.1 inactivation in beta-cells from
      iPLA(2)beta(-/-) mice. Stably transfected INS-1 cells that overexpress
      iPLA(2)beta hydrolyze phospholipids more rapidly than control INS-1 cells and
      also exhibit an increase in the inactivation rate of the delayed rectifier
      currents. These results suggest that Kv2.1 currents could be dynamically
      modulated in the pancreatic islet beta-cell by phospholipase-catalyzed hydrolysis
      of membrane phospholipids to yield non-esterified fatty acids, such as AA, that
      facilitate Ca(2+) entry and insulin secretion.

PMID- 17197454
TI  - Microcytic anemia.

PMID- 17197455
TI  - Oral conditions.

PMID- 17197456
TI  - Pediatrics in the community: the Earn-a-Bike program.

PMID- 17197457
TI  - Index of suspicion.

PMID- 17197458
TI  - Anemia and polycythemia in the newborn.

PMID- 17197459
TI  - Opiate overdose.

PMID- 17197460
TI  - Retinoblastoma.

PMID- 17197462
TI  - The role of combined spinal epidural analgesia for labour: is there still a
      question?

PMID- 17197463
TI  - Intrathecal plain vs hyperbaric bupivacaine for labour analgesia: efficacy and
      side effects.
AB  - PURPOSE: Baricity is an important determinant of block characteristics of the
      spinal component of a combined spinal epidural (CSE) for labour analgesia. This
      study compares the analgesic efficacy and side effects of intrathecally
      administered plain and hyperbaric bupivacaine (both with fentanyl) during active
      labour. METHODS: Sixty-two women in active labour (cervical dilatation >or=5 cm
      and pain score > 5) were randomized in a prospective, single-blinded fashion to
      receive 2.5 mg of either hyperbaric or plain bupivacaine both combined with 15
      microg of fentanyl as the spinal component of a CSE. The primary outcome was
      failure of satisfactory analgesia within ten minutes of the intrathecal injection
      as defined by a verbal pain score > 3. Secondary outcomes included need for
      rescue analgesia, hypotension, respiratory depression, nausea and vomiting,
      pruritus and sustained fetal bradycardia. RESULTS: Sixty patients were analyzed.
      The failure rates were 20% in the hyperbaric group vs 0% in the plain group
      (P=0.024). The plain solution provided faster onset, higher sensory levels and
      less motor block at all times during the first 30 min. The incidence of both
      pruritus and sustained fetal bradycardia was 33% in the plain group and 10% in
      the hyperbaric group (P=0.03). CONCLUSION: A plain rather than hyperbaric
      solution of bupivacaine 2.5 mg with fentanyl 15 microg provides a faster onset of
      analgesia, higher sensory levels and less motor block, while demonstrating an
      increased incidence of pruritus and sustained fetal bradycardia.

PMID- 17197464
TI  - Effect of stylet angulation and endotracheal tube camber on time to intubation
      with the GlideScope.
AB  - PURPOSE: The GlideScope videolaryngoscope usually provides excellent glottic
      visualization, but directing an endotracheal tube (ETT) through the vocal cords
      is sometimes difficult. The goal of the study was to determine which of two ETT
      angles (60 degrees vs 90 degrees ) and cambers (forward vs reverse) was better,
      as determined by time to intubation (TTI). METHODS: Two hundred patients
      requiring orotracheal intubation for elective surgery were randomly allocated to
      one of four groups: A) 90 degrees angle, forward camber; B) 90 degrees angle,
      reverse camber; C) 60 degrees angle, forward camber; D) 60 degrees angle, reverse
      camber. Time to intubation was assessed by a blinded observer. Operators were
      blinded until the point of intubation. A visual analogue scale (VAS) assessed the
      ease of intubation. The number of intubation attempts, number of failures,
      glottic grades, and use of external laryngeal manipulation were recorded.
      RESULTS: The angle of the ETT had an impact on TTI but camber did not. The 90
      degrees angle demonstrated a 13% faster TTI than the 60 degrees angle (47.1 +/-
      21.2 sec vs 54.4 +/- 28.2 sec, P=0.042), and it resulted in easier intubation
      (VAS 16.4 +/- 14.2 mm vs 27.3 +/- 23.5 mm, P=0.0001). The overall incidence of a
      grade 1 or 2 Cormack-Lehane glottic view was 99%. CONCLUSIONS: In a heterogeneous
      group of operators and patients intubated with the GlideScope, a 90 degrees ETT
      angle provided the best result and should be the initial configuration. The
      camber of the ETT does not affect the time to intubation.

PMID- 17197465
TI  - Performance of the PAxpress vs the ProSeal laryngeal mask airway during general
      anesthesia.
AB  - PURPOSE: The PAxpress (PAx) is a relatively new pharyngeal airway device that is
      easily inserted and effective in routine airway management. A prospective,
      randomized study was undertaken to compare the PAx with the ProSeal laryngeal
      mask airway (PLMA) during anesthesia with positive pressure ventilation. METHODS:
      One hundred adult patients scheduled for elective surgery under general
      anesthesia were randomized to airway management with either the PAx (n=50) or the
      PLMA (n=50). All patients swallowed a methylene blue capsule before anesthesia.
      After insertion, leak and inspiratory pressures were measured. Fibrescopy was
      used to view the glottis. Devices were inspected for blood or methylene blue
      staining upon removal at the end of surgery. An interview was conducted
      postoperatively to evaluate the occurrence of sore throat, dysphagia and
      dysphonia. RESULTS: Insertion time was longer for the PAx than for the PLMA (52
      +/- 44s vs 34 +/- 23 sec; P=0.003). Leak pressure was lower while peak
      inspiratory pressures, and EtCO2 values were higher (P=0.016; 0.027 and 0.04
      respectively) with the PAx. Both devices provided comparable fibreoptic viewing
      of the glottis. There were no differences with respect to the incidence or
      pattern of blue stains upon removal. Blood was seen more often on the PAx (58% vs
      19%) and dysphagia was also more frequent and severe with the PAx. CONCLUSION: In
      comparison with the PLMA, PAx insertion time is longer and the ventilatory
      characteristics of this new device may be marginally inferior. The PAx is also
      more traumatic and is associated with more postoperative discomfort compared to
      the PLMA.

PMID- 17197466
TI  - Efficacy of forced-air warming systems with full body blankets.
AB  - PURPOSE: Postoperative hypothermia after cardiac surgery is still a common
      problem often treated with forced-air warming. This study was conducted to
      determine the heat transfer efficacy of 11 forced-air warming systems with full
      body blankets on a validated copper manikin. METHODS: The following systems were
      tested: 1) Bair Hugger 505; 2) Bair Hugger 750; 3) Life-Air 1000 S; 4) Snuggle
      Warm; 5) Thermacare; 6) Thermacare with reusable Optisan blanket; 7) WarmAir; 8)
      Warm-Gard; 9) Warm-Gard and reusable blanket; 10) WarmTouch; and 11) WarmTouch
      and reusable blanket. Heat transfer of forced-air warmers can be described as
      follows: Q = h x DeltaT x A. Where Q = heat flux (W), h = heat exchange
      coefficient (W x m-2 x degrees C-1), DeltaT = temperature gradient between
      blanket and manikin surface (degrees C), A = covered area (m2). Heat flux per
      unit area and surface temperature were measured with 16 heat flux transducers.
      Blanket temperature was measured using 16 thermocouples. The temperature gradient
      between blanket and surface (DeltaT) was varied and h was determined by linear
      regression analysis. Mean DeltaT was determined for surface temperatures between
      32 degrees C and 38 degrees C. The covered area was estimated to be 1.21 m2.
      RESULTS: For the 11 devices, heat transfers of 30.7 W to 77.3 W were observed for
      surface temperatures of 32 degrees C, and between -8.8 W to 29.6 W for surface
      temperatures of 38 degrees C. CONCLUSION: There are clinically relevant
      differences between the tested forced-air warming systems with full body
      blankets. Several systems were unable to transfer heat to the manikin at a
      surface temperature of 38 degrees C.

PMID- 17197467
TI  - Effect of ischemic post-conditioning on spinal cord ischemic-reperfusion injury
      in rabbits.
AB  - OBJECTIVES: To investigate the potential protective effect of ischemic post
      conditioning (Post-con) on ischemia-reperfusion injury of the rabbit spinal cord,
      and to determine if there is an additive neuroprotective effect when ischemic
      preconditioning (IPC) and Post-con are combined. METHODS: Forty New Zealand white
      rabbits were randomly divided into four groups: group Control (C; n=10), aortic
      occlusion (AOC; for 30 min; group IPC (n=10) three cycles of three-minute AOC
      plus three-minute reperfusion before the 30-min AOC; group Post-con (n=10), three
      cycles of three-minute reperfusion plus three-minute AOC immediately upon
      reperfusion after 30-min AOC; group IPC+Post-con (n=10), where animals were
      subjected to both IPC and Post-con. At six hours, 24 hr and 48 hr following
      reperfusion, neurological function was assessed according to Tarlov scores, and
      at 48 hr, the spinal cords were procured for the histopathologic evaluation, by
      comparing the number of intact alpha-motor neurons in the anterior horn. RESULTS:
      The median count (and quartiles) of intact alpha-motor neurons was greatest in
      group Post-con 73 (69-76) and group IPC+Post-con 29 (22-42) compared to the
      numbers of viable alpha-motor neurons in groups C 6 (4-9) and IPC 15 (11-18) (P <
      0.001). The numbers of animals who developed paraplegia according to Tarlov
      criteria were 7/10 in groups Post-con and IPC+Post-con, compared to 9/10 animals
      in each of groups C and IPC. CONCLUSIONS: This laboratory investigation provides
      histological evidence that Post-con may protect the spinal cord from moderate to
      severe ischemia reperfusion injury. Ischemic preconditioning conferred no
      additional benefits in this rabbit model. The results have potential clinical
      implications for patients undergoing thoracoabdominal aortic reconstructive
      surgery.

PMID- 17197468
TI  - Encephalopathy and rhabdomyolysis induced by iotrolan during epiduroscopy.
AB  - PURPOSE: We describe a complication of epiduroscopy with encephalopathy and
      rhabdomyolysis associated with the contrast medium iotrolan. CLINICAL FEATURES: A
      76-yr-old man with failed back surgery syndrome underwent epiduroscopy.
      Sufficient lysis could not be achieved in the epidural space above the level of
      L4 due to dense adhesions and scar tissue. After epidural injections of iotrolan
      and mepivacaine, he developed motor weakness and hypoesthesia in both legs, which
      lasted for three hours. He also became confused, agitated, disoriented, and
      developed neck stiffness and tremors involving the head and legs. Computed
      tomography revealed diffuse contrast enhancement within the intracranial
      cerebrospinal fluid (CSF) spaces, indicating an intraoperative dural tear. Marked
      increases in serum creatinine phosphokinase and myoglobin indicated subsequent
      acute rhabdomyolysis. Crystalloid infusion and semi-recumbent positioning
      facilitated iotrolan absorption from the CSF, and the patient recovered
      uneventfully. CONCLUSIONS: Dural tear during epiduroscopy may allow access of
      contrast media into the CSF. Neurotoxicity secondary to iotrolan within the CSF
      was a likely contributing factor to the encephalopathy and subsequent
      rhabdomyolysis. This is an instructive example of the importance of diagnosing
      inadvertent dural tear during epiduroscopy under iotrolan, for avoidance of
      adverse events such as encephalopathy and rhabdomyolysis.

PMID- 17197469
TI  - Complications associated with the use of the GlideScope videolaryngoscope.
AB  - PURPOSE: Two cases are presented wherein the GlideScope videolaryngoscope (GVL)
      facilitated laryngeal exposure and successful endotracheal intubation, but
      resulted in pharyngeal injury. CLINICAL FEATURES: GlideScope videolaryngoscopy
      was performed in two female patients, whose airways were anticipated to present
      difficulties for direct laryngoscopy. In the first case, following induction of
      anesthesia, moderate difficulty was encountered in directing the endotracheal
      tube (ETT) into the patient's larynx. In the second case, minimal difficulty with
      the GVL was experienced, and no problems were identified with airway
      instrumentation until the drapes covering the patient's face were removed. In
      both instances, the ETT had passed through the right palatopharyngeal arch,
      requiring suturing in the first patient, and electrocautery in the second
      patient. CONCLUSION: There have been no previously published reports of injuries
      related to GlideScope laryngoscopy, but perforation of the palatopharyngeal arch
      occurring in two patients demonstrates a rare but potentially important
      complication of the GVL. Strategies to minimize this complication are considered.

PMID- 17197470
TI  - Brief review: Neuromuscular monitoring: an update for the clinician.
AB  - PURPOSE: To review established techniques and to provide an update on new methods
      for clinical monitoring of neuromuscular function relevant to anesthesia. SOURCE:
      A PubMed search of relevant article for the period 1985-2005 was undertaken, and
      bibliographies were scanned for additional sources. PRINCIPAL FINDINGS: There is
      no substitute for objective neuromuscular monitoring; for research purposes,
      mechanomyography (MMG) is the gold standard; however, the most versatile method
      in the clinical setting is acceleromyography since it can be applied at various
      muscles and has a long track record of clinical utility. Kinemyography is valid
      to monitor recovery of neuromuscular transmission at the adductor pollicis muscle
      (AP), whereas phonomyography is easy to apply to various muscles and shows
      promising agreement with MMG. Monitoring of the corrugator supercilii muscle (CS)
      may be used to determine the earliest time for tracheal intubation as it reflects
      laryngeal relaxation better than monitoring at the AP. Recovery of neuromuscular
      transmission is best monitored at the AP, since it is the last muscle to recover
      from neuromuscular blockade (NMB). If train-of-four (TOF) stimulation is used, a
      TOF-ratio > 0.9 should be the target before awakening the patient. If surgery or
      the type of anesthesia necessitates NMB of a certain degree, e.g., TOF-ratio =
      0.25, monitoring of muscles which best reflect the degree of NMB at the surgical
      site is preferable. CONCLUSION: Objective methods should be used to monitor
      neuromuscular function in clinical anesthesia. Acceleromyography offers the best
      compromise with respect to ease of use, practicality, versatility, precision and
      applicability at various muscles. The CS is the optimal muscle to determine the
      earliest time for intubation, e.g., for rapid sequence induction.

PMID- 17197471
TI  - Best evidence in critical care medicine: Fluid management in acute lung injury:
      friend or foe?

PMID- 17197472
TI  - Lessons in drug development.

PMID- 17197473
TI  - Tracheal intubation using the GlideScope with a combined curved pipe stylet, and
      endotracheal tube introducer.

PMID- 17197474
TI  - Knotting in peripherally inserted central catheters: more possible mechanisms.

PMID- 17197476
TI  - Insertion of the LMA ProSeal using the Satin-Slip intubating stylet.

PMID- 17197475
TI  - Dose-response and postoperative confusion following methylene blue infusion
      during parathyroidectomy.

PMID- 17197477
TI  - What else can you expect at www.erj.ersjournals.com?

PMID- 17197478
TI  - Requisite for stringent control of oxygen therapy in the neonatal period.

PMID- 17197479
TI  - Screening for lung cancer in a high-risk group: but I still haven't found what
      I'm looking for...

PMID- 17197480
TI  - Tumour necrosis factor and lymphotoxin A polymorphisms: a relationship with COPD
      and its progression?

PMID- 17197481
TI  - The human lung: did evolution get it wrong?
AB  - Some 300 million yrs ago, the ancestors of modern reptiles emerged from water and
      were committed to air breathing. They were exothermic and incapable of sustained
      levels of high physical activity. But from them evolved the two great classes of
      vertebrates with high levels of maximal oxygen consumption: the mammals and
      birds. A remarkable feature of these two divergent evolutionary lines is that,
      although the physiology of many organ systems shows many similarities, the lungs
      are radically different. A major difference is that the ventilation of the gas
      exchanging tissue has a flow-through pattern in the bird but is reciprocating in
      the mammal. The result is that mammals have a reduced alveolar and arterial
      oxygen tension, a potential for uneven ventilation, and relatively large terminal
      air spaces. This in turn means that the pulmonary capillaries are poorly
      supported compared with the bird. The result is that the pulmonary capillaries in
      the bird have much thinner and more uniform walls, with more efficient gas
      exchange. Other advantages of the bird lung are that it utilises a more efficient
      cross-current pattern of gas-exchange, and the bird has separated the ventilatory
      and gas exchange functions. From a structure-function standpoint, the bird lung
      is superior.

PMID- 17197482
TI  - Sleep apnoea as an independent risk factor for cardiovascular disease: current
      evidence, basic mechanisms and research priorities.
AB  - Considerable evidence is available in support of an independent association
      between obstructive sleep apnoea syndrome (OSAS) and cardiovascular disease,
      which is particularly strong for systemic arterial hypertension and growing for
      ischaemic heart disease, stroke, heart failure, atrial fibrillation and cardiac
      sudden death. The pathogenesis of cardiovascular disease in OSAS is not
      completely understood but likely to be multifactorial, involving a diverse range
      of mechanisms including sympathetic nervous system overactivity, selective
      activation of inflammatory molecular pathways, endothelial dysfunction, abnormal
      coagulation and metabolic dysregulation, the latter particularly involving
      insulin resistance and disordered lipid metabolism. The present report, which
      arose out of a European Union Cooperation in the field of Scientific and
      Technical Research (COST) action on OSAS (COST B26), reviews the current evidence
      for an independent association and proposes research priorities to identify the
      underlying mechanisms involved, with a view to identifying novel therapeutic
      strategies. Large-scale collaborative studies of carefully defined patient
      populations with obstructive sleep apnoea syndrome, adequately controlled for
      potential confounders, are needed. Such studies carry the prospect of evaluating
      potential interactions between different basic mechanisms operating in
      obstructive sleep apnoea syndrome and cardiovascular disease, and interactions
      with other related disorders, such as obesity, diabetes and dyslipidaemia.
      Furthermore, translational studies involving cell culture and animal models
      linked to studies of obstructive sleep apnoea syndrome patients are necessary to
      integrate basic mechanisms with the clinical disorder.

PMID- 17197483
TI  - Genes, environments, development and asthma: a reappraisal.
AB  - Significant advances have been made in our understanding of the role of genetic
      variation in determining complex human phenotypes such as asthma. It is now well
      established that there is no single "gene for asthma", in the way that the cystic
      fibrosis transmembrane receptor is the "gene for cystic fibrosis". It is also
      clear that among all genetic variants eventually found to be associated with
      asthma, only a few will be replicated, and in the same direction, in the majority
      of well-performed studies. Current evidence suggests that most asthma-related
      polymorphisms determine risk for the disease in a context-dependent manner, i.e.
      they interact with environmental factors, with polymorphisms in other genes and
      with the specific developmental phase of the disease in which the association is
      tested. Elucidating these complex interactions will allow us to understand better
      the heterogeneity of the disease and thus to develop therapeutic tools tailored
      to the specific form of the disease in each patient.

PMID- 17197484
TI  - Recommendations on the use of exercise testing in clinical practice.
AB  - Evidence-based recommendations on the clinical use of cardiopulmonary exercise
      testing (CPET) in lung and heart disease are presented, with reference to the
      assessment of exercise intolerance, prognostic assessment and the evaluation of
      therapeutic interventions (e.g. drugs, supplemental oxygen, exercise training). A
      commonly used grading system for recommendations in evidence-based guidelines was
      applied, with the grade of recommendation ranging from A, the highest, to D, the
      lowest. For symptom-limited incremental exercise, CPET indices, such as peak O(2)
      uptake (V'O(2)), V'O(2) at lactate threshold, the slope of the ventilation-CO(2)
      output relationship and the presence of arterial O(2) desaturation, have all been
      shown to have power in prognostic evaluation. In addition, for assessment of
      interventions, the tolerable duration of symptom-limited high-intensity constant
      load exercise often provides greater sensitivity to discriminate change than the
      classical incremental test. Field-testing paradigms (e.g. timed and shuttle
      walking tests) also prove valuable. In turn, these considerations allow the
      resolution of practical questions that often confront the clinician, such as: 1)
      "When should an evaluation of exercise intolerance be sought?"; 2) "Which
      particular form of test should be asked for?"; and 3) "What cluster of variables
      should be selected when evaluating prognosis for a particular disease or the
      effect of a particular intervention?"

PMID- 17197485
TI  - Population-specific reference equations?

PMID- 17197486
TI  - Improvement of endothelial function with allopurinol may occur in selected
      patients with OSA: effect of age and sex.

PMID- 17197487
TI  - ACE inhibitors prevent aspiration pneumonia in Asian, but not Caucasian, elderly
      patients with stroke.

PMID- 17197488
TI  - PDE-5 inhibitors lower portal and pulmonary pressure in portopulmonary
      hypertension.

PMID- 17197489
TI  - Differentiating phonotactic probability and neighborhood density in adult word
      learning.
AB  - PURPOSE: The purpose of this study was to differentiate effects of phonotactic
      probability, the likelihood of occurrence of a sound sequence, and neighborhood
      density, the number of words that sound similar to a given word, on adult word
      learning. A second purpose was to determine what aspect of word learning (viz.,
      triggering learning, formation of an initial representation, or integration with
      existing representations) was influenced by each variable. METHOD: Thirty-two
      adults were exposed to 16 nonwords paired with novel objects in a story context.
      The nonwords orthogonally varied in phonotactic probability and neighborhood
      density. Learning was measured following 1, 4, and 7 exposures in a picture
      naming task. Partially correct (i.e., 2 of 3 phonemes correct) and completely
      correct responses (i.e., 3 of 3 phonemes correct) were analyzed together and
      independently to examine emerging and partial representations of new words versus
      complete and accurate representations of new words. RESULTS: Analysis of
      partially correct and completely correct responses combined showed that adults
      learned a lower proportion of high-probability nonwords than low-probability
      nonwords (i.e., high-probability disadvantage) and learned a higher proportion of
      high-density nonwords than low-density nonwords (i.e., high-density advantage).
      Separate analysis of partially correct responses yielded an effect of phonotactic
      probability only, whereas analysis of completely correct responses yielded an
      effect of neighborhood density only. CONCLUSIONS: These findings suggest that
      phonological and lexical processing influence different aspects of word learning.
      In particular, phonotactic probability may aid in triggering new learning,
      whereas neighborhood density may influence the integration of new lexical
      representations with existing representations.

PMID- 17197490
TI  - The dimensionality of language ability in school-age children.
AB  - PURPOSE: This study asked if children's performance on language tests reflects
      different dimensions of language and if this dimensionality changes with
      development. METHOD: Children were given standardized language batteries at
      kindergarten and at second, fourth, and eighth grades. A revised modified
      parallel analysis was used to determine the dimensionality of these items at each
      grade level. A confirmatory factor analysis was also performed on the subtest
      scores to evaluate alternate models of dimensionality. RESULTS: The revised
      modified parallel analysis revealed a single dimension across items with evidence
      of either test specific or language area specific minor dimensions at different
      ages. The confirmatory factor analysis tested models involving modality
      (receptive or expressive) and domain (vocabulary or sentence use) against a
      single-dimension model. The 2-dimensional model involving domains of vocabulary
      and sentence use fit the data better than the single-dimensional model; however,
      the single-dimension model also fit the data well in the lower grades.
      CONCLUSIONS: Much of the variance in standardized measures of language appears to
      be attributable to a single common factor or trait. There is a developmental
      trend during middle childhood for grammatical abilities and vocabulary abilities
      to become differentiated. These measures do not provide differential information
      concerning receptive and expressive abilities.

PMID- 17197491
TI  - Evaluating the discriminant accuracy of a grammatical measure with Spanish
      speaking children.
AB  - PURPOSE: The purpose of this study was to evaluate the discriminant accuracy of a
      grammatical measure for the identification of language impairment in Latino
      Spanish-speaking children. The authors hypothesized that if exposure to and use
      of English as a second language have an effect on the first language, bilingual
      children might exhibit lower rates of grammatical accuracy than their peers and
      be more likely to be misclassified. METHOD: Eighty children with typical language
      development and 80 with language impairment were sampled from 4 different
      geographical regions and compared using linear discriminant function analysis.
      RESULTS: Results indicated fair-to-good sensitivity from 4;0 to 5;1 years, good
      sensitivity from 5;2 to 5;11 years, and poor sensitivity above age 6 years. The
      discriminant functions derived from the exploratory studies were able to predict
      group membership in confirmatory analyses with fair-to-excellent sensitivity up
      to age 6 years. Children who were bilingual did not show lower scores and were
      not more likely to be misclassified compared with their Spanish-only peers.
      CONCLUSIONS: The measure seems to be appropriate for identifying language
      impairment in either Spanish-dominant or Spanish-only speakers between 4 and 6
      years of age. However, for older children, supplemental testing is necessary.

PMID- 17197492
TI  - Prelinguistic predictors of language outcome at 3 years of age.
AB  - PURPOSE: The purpose of this study was to examine the predictive validity of a
      collection of prelinguistic skills measured longitudinally in the 2nd year of
      life to language outcome in the 3rd year in children with typical language
      development. METHOD: A collection of prelinguistic skills was assessed in 160
      children early (M = 14.31 months; SD = 1.36) and late (M = 19.76 months; SD =
      1.16) in their 2nd year by using the Communication and Symbolic Behavior Scales
      Developmental Profile Behavior Sample (A. Wetherby & B. Prizant, 2002). The
      relation between the prelinguistic skills and the receptive and expressive
      language near the 3rd birthday was examined. RESULTS: Significant correlations
      were observed between many prelinguistic skills and language outcome. Regression
      analyses indicated that comprehension both early and late contributed unique
      variance to receptive and expressive language outcome. In addition, early in the
      2nd year, inventory of conventional gestures contributed uniquely to receptive
      language outcome, and acts for joint attention contributed uniquely to expressive
      outcome. Late in the 2nd year, inventory of consonants contributed uniquely to
      expressive outcome. CONCLUSIONS: The findings demonstrate continuity between
      prelinguistic and linguistic skills and how individual differences in a number of
      prelinguistic skills contribute collectively and uniquely to language outcome in
      typically developing children.

PMID- 17197493
TI  - Effects of acoustic manipulation on the real-time inflectional processing of
      children with specific language impairment.
AB  - PURPOSE: This study reports the findings of an investigation designed to examine
      the effects of acoustic enhancement on the processing of low-phonetic-substance
      inflections (e.g., 3rd-person singular -s, possessive -s) versus a high-phonetic
      substance inflection (e.g., present progressive -ing) by children with specific
      language impairment (SLI) in a word recognition, reaction time (RT) processing
      task. The effects of acoustic enhancement on the processing of the same morphemes
      as well as an additional morpheme (comparative -er) were examined in an offline
      grammaticality judgment task. The grammatical function of 1 of the higher
      phonetic-substance inflections, -ing, was presumed to be hypothesized relatively
      early by children; the function of the other, -er, was presumed to be
      hypothesized relatively late. METHOD: Sixteen children with SLI (age(M) = 9
      years;0 months) and 16 chronological age (CA; age(M) = 8;11) children
      participated. For both tasks, children listened to sentences containing the
      target morphemes as they were produced naturally (natural condition) or with
      acoustic enhancement (enhanced condition). RESULTS: On the RT task, the children
      with SLI demonstrated RT sensitivity only to the presence of the high-substance
      inflection, irrespective of whether it was produced naturally or with
      enhancement. Acoustic enhancement had no effect on these children's processing of
      low-substance inflections. The CA children, by contrast, showed sensitivity to
      low-substance inflections when they were produced naturally and with acoustic
      enhancement. These children also showed sensitivity to the high-substance
      inflection in the natural condition, but in the enhanced condition they
      demonstrated significantly slower RT. On the grammaticality judgment task, the
      children with SLI performed worse than the CA children overall and showed
      especially poor performance on low-substance inflections. Acoustic enhancement
      had a beneficial effect on the inflectional processing of the children with SLI,
      but it had no effect on CA children. CONCLUSION: The findings are interpreted to
      suggest that the reduced language processing capacity of children with SLI
      constrains their ability to process low-substance grammatical material in real
      time. This factor should be considered along with any difficulty that might be
      attributable to the grammatical function of the inflection.

PMID- 17197494
TI  - Subcategory learning in normal and language learning-disabled adults: how much
      information do they need?
AB  - PURPOSE: The purpose of this experiment was to determine if nonreferential
      morphophonological information was sufficient to facilitate the learning of
      gender subcategories (i.e., masculine vs. feminine) in individuals with normal
      language (NL) and those with a history of language-based learning disabilities
      (HLD). METHOD: Thirty-two adults listened for 18 min to a familiarization set of
      Russian words that included either 1 (single-marked) or 2 (double-marked)
      morphophonological markers indicating gender. Participants were then tested on
      their knowledge of both trained and untrained members of each gender subcategory.
      RESULTS: Testing indicated that morphophonological information is sufficient for
      lexical subcategory learning in both NL and HLD groups, although the HLD group
      had lower overall accuracy. The HLD group benefited from double-marking relative
      to single-marking for subcategory learning. CONCLUSION: The results demonstrated
      that learning through implicit mechanisms occurred after a relatively brief
      exposure to the language stimuli. In addition, the weaker overall learning by the
      HLD group was facilitated when multiple cues to linguistic subcategory were
      available in the input group members received.

PMID- 17197495
TI  - Understanding conservation delays in children with specific language impairment:
      task representations revealed in speech and gesture.
AB  - PURPOSE: The authors investigated mental representations of Piagetian
      conservation tasks in children with specific language impairment (SLI) and
      typically developing peers. Children with SLI have normal nonverbal intelligence;
      however, they exhibit difficulties in Piagetian conservation tasks. The authors
      tested the hypothesis that conservation difficulties may be due to the degree to
      which children with SLI rely on external perceptual features of the task as
      opposed to internal cognitive knowledge about transformation. METHOD: Twenty-nine
      children participated, 12 children with SLI (ages 7;0-10;5) and 17 typically
      developing peers (ages 5;4-10;9) who were matched either on chronological age
      (CA) task or on judgments on the conservation task (conservation matched [CM]).
      Children solved conservation tasks and then explained their reasoning.
      Explanations produced in speech and gesture were analyzed. RESULTS: In speech,
      children in the SLI group expressed proportionately fewer internal explanations
      than the CA group, but a similar proportion of internal explanations as compared
      with the younger CM group. In gesture, children with SLI did not differ from
      either CA or CM children. CONCLUSIONS: Children with SLI have weak internal
      representations of the concept of conservation, similar to those of younger
      children. Conservation representations appear to be closely related to language
      skills and verbal working memory.

PMID- 17197497
TI  - The genetic bases of speech sound disorders: evidence from spoken and written
      language.
AB  - The purpose of this article is to review recent findings suggesting a genetic
      susceptibility for speech sound disorders (SSD), the most prevalent communication
      disorder in early childhood. The importance of genetic studies of SSD and the
      hypothetical underpinnings of these genetic findings are reviewed, as well as
      genetic associations of SSD with other language and reading disabilities. The
      authors propose that many genes contribute to SSD. They further hypothesize that
      some genes contribute to SSD disorders alone, whereas other genes influence both
      SSD and other written and spoken language disorders. The authors postulate that
      underlying common cognitive traits, or endophenotypes, are responsible for shared
      genetic influences of spoken and written language. They review findings from
      their genetic linkage study and from the literature to illustrate recent
      developments in this area. Finally, they discuss challenges for identifying
      genetic influence on SSD and propose a conceptual framework for study of the
      genetic basis of SSD.

PMID- 17197496
TI  - Children's history of speech-language difficulties: genetic influences and
      associations with reading-related measures.
AB  - PURPOSE: This study examined (a) the extent of genetic and environmental
      influences on children's articulation and language difficulties and (b) the
      phenotypic associations between such difficulties and direct assessments of
      reading-related skills during early school-age years. METHOD: Behavioral genetic
      analyses focused on parent-report data regarding the speech-language skills of
      248 twin pairs (M = 6.08 years) from the Western Reserve Reading Project. In
      addition, phenotypic associations between children's speech-language status and
      direct assessments of early reading-related abilities were examined through
      hierarchical linear modeling (HLM). RESULTS: Probandwise concordance rates and
      intraclass tetrachoric correlations indicated high heritability for children's
      difficulties in expressive language and articulation, with estimates of .54 and
      .97 accordingly. HLM results indicated that children with histories of speech
      language difficulties scored significantly lower than unaffected children on
      various measures of early reading-related abilities. CONCLUSIONS: Results from
      the parent-report survey provided converging evidence of genetic effects on
      children's speech and language difficulties and suggest that children with a
      history of speech-language difficulties are at risk for lower performance on
      early reading-related measures. The extent of risk differed across measures and
      appeared greatest for children who demonstrated a history of difficulties across
      articulation, expressive language, and receptive language. Implications for
      future genetic research and clinical practice are discussed.

PMID- 17197498
TI  - Dysgraphia in Alzheimer's disease: a review for clinical and research purposes.
AB  - PURPOSE: This article presents a critical review of literature on dysgraphia
      associated with Alzheimer's disease (AD). Research presented includes discussions
      of central and peripheral spelling impairments as well as the impact of general,
      nonlinguistic cognitive functions on dysgraphia associated with AD. METHOD: The
      studies critically reviewed were from a variety of disciplines, with emphasis on
      seminal work, recent literature, and the first author's research. CONCLUSIONS:
      Studies have shown that writing impairment is heterogeneous within the AD
      population; however, there are certain aspects of the writing process that are
      more vulnerable than others and may serve as diagnostic signs. Identifying
      patterns of writing impairment at different stages of AD may help to chart
      disease progression and assist in the development of appropriate interventions.

PMID- 17197499
TI  - Effects of talker variability on vowel recognition in cochlear implants.
AB  - PURPOSE: To investigate the effects of talker variability on vowel recognition by
      cochlear implant (CI) users and by normal-hearing (NH) participants listening to
      4-channel acoustic CI simulations. METHOD: CI users were tested with their
      clinically assigned speech processors. For NH participants, 3 CI processors were
      simulated, using different combinations of carrier type and temporal envelope
      cutoff frequency (noise band/160 Hz, sine wave/160 Hz, and sine wave/20 Hz).
      Vowel recognition was measured for 4 talkers, presented in either a single-talker
      context (1 talker per test block) or a multi-talker context (4 talkers per test
      block). RESULTS: CI users' vowel recognition was significantly poorer in the
      multi-talker context than in the single-talker context. When noise-band carriers
      were used in the simulations, NH performance was not significantly affected by
      talker variability. However, when sine-wave carriers were used in the
      simulations, NH performance was significantly affected by talker variability in
      both envelope filter conditions. CONCLUSIONS: Because fundamental frequency was
      not preserved by the 20-Hz envelope filter and only partially preserved by the
      160-Hz envelope filter, both spectral and temporal cues contributed to the talker
      variability effects observed with sine-wave carriers. Similarly, spectral and
      temporal cues may have contributed to the talker variability effects observed
      with CI participants.

PMID- 17197500
TI  - Phonological abilities of hearing-impaired Cantonese-speaking children with
      cochlear implants or hearing AIDS.
AB  - PURPOSE: This article examined the phonological skills of 2 groups of Cantonese
      speaking children with prelingual, profound bilateral hearing loss. The
      phonological abilities of 7 children fitted with hearing aids were compared with
      the abilities of 7 children who wore cochlear implants. METHOD: Participants in
      each group ranged in age from 5;1 to 6;4 years. The participants were asked to
      name 57 pictures and retell 2 stories. Phonological abilities were described in
      terms of the participants' phonological units and the phonological processes
      used. The participants' perception of single words was assessed using a Cantonese
      phonology test that includes tonal, segmental, and semantic distracters. RESULTS:
      All except 1 participant had incomplete phonetic repertories. All participants
      showed complete vowel and tone inventories. The study group used both
      developmental rules and nondevelopmental phonological rules. For perception of
      single words, participants chose the target word most often. The cochlear implant
      users had a significantly higher percentage correct score for consonant
      production than hearing aid users. CONCLUSIONS: The prediction that Cantonese
      children wearing cochlear implants would have better phonological skills than
      children having hearing aids with a similar degree of hearing loss was confirmed.
      Cochlear implant usage appeared to promote consonant feature production
      development to a greater degree than did the use of a hearing aid.

PMID- 17197501
TI  - The effect of hearing loss on identification of asynchronous double vowels.
AB  - This study determined whether listeners with hearing loss received reduced
      benefits due to an onset asynchrony between sounds. Seven normal-hearing
      listeners and 7 listeners with hearing impairment (HI) were presented with 2
      synthetic, steady-state vowels. One vowel (the late-arriving vowel) was 250 ms in
      duration, and the other (the early-arriving vowel) varied in duration between 350
      and 550 ms. The vowels had simultaneous offsets, and therefore an onset
      asynchrony between the 2 vowels ranged between 100 and 300 ms. The early-arriving
      and late-arriving vowels also had either the same or different fundamental
      frequencies. Increases in onset asynchrony and differences in fundamental
      frequency led to better vowel-identification performance for both groups, with
      listeners with HI benefiting less from onset asynchrony than normal-hearing
      listeners. The presence of fundamental frequency differences did not influence
      the benefit received from onset asynchrony for either group. Excitation pattern
      modeling indicated that the reduced benefit received from onset asynchrony was
      not easily predicted by the reduced audibility of the vowel sounds for listeners
      with HI. Therefore, suprathreshold factors such as loss of the cochlear
      nonlinearity, reduced temporal integration, and the perception of vowel dominance
      probably play a greater role in the reduced benefit received from onset
      asynchrony in listeners with HI.

PMID- 17197503
TI  - Reaction times of normal listeners to laryngeal, alaryngeal, and synthetic
      speech.
AB  - The purpose of this study was to compare listener processing demands when
      decoding alaryngeal compared to laryngeal speech. Fifty-six listeners were
      presented with single words produced by 1 proficient speaker from 5 different
      modes of speech: normal, tracheosophageal (TE), esophageal (ES), electrolaryngeal
      (EL), and synthetic speech (SS). Cognitive processing load was indexed by
      listener reaction time (RT). To account for significant durational differences
      among the modes of speech, an RT ratio was calculated (stimulus duration divided
      by RT). Results indicated that the cognitive processing load was greater for ES
      and EL relative to normal speech. TE and normal speech did not differ in terms of
      RT ratio, suggesting fairly comparable cognitive demands placed on the listener.
      SS required greater cognitive processing load than normal and alaryngeal speech.
      The results are discussed relative to alaryngeal speech intelligibility and the
      role of the listener. Potential clinical applications and directions for future
      research are also presented.

PMID- 17197502
TI  - Effects of increasing sound pressure level on lip and jaw movement parameters and
      consistency in young adults.
AB  - PURPOSE: Examination of movement parameters and consistency has been used to
      infer underlying neural control of movement. However, there has been no
      systematic investigation of whether the way individuals are asked (or cued) to
      increase loudness alters articulation. This study examined whether different cues
      to elicit louder speech induce different lip and jaw movement parameters or
      consistency. METHOD: Thirty healthy young adults produced two sentences (a) at
      comfortable loudness, (b) while targeting 10 dB SPL above comfortable loudness on
      a sound level meter, (c) at twice their perceived comfortable loudness, and (d)
      while multitalker noise was played in the background. Lip and jaw kinematics and
      acoustic measurements were taken. RESULTS: Each of the loud conditions resulted
      in a similar amount of SPL increase, about 10 dB. Speech rate was slower in the
      background noise condition. Changes to movement parameters and consistency
      (relative to comfortable) were different in the targeting condition as compared
      to the other loud conditions. CONCLUSIONS: The cues elicited different task
      demands, and therefore, different movement patterns were used by the speakers to
      achieve the target of increased loudness. Based on these results, cueing should
      be considered when eliciting increased vocal loudness in both clinical and
      research situations.

PMID- 17197504
TI  - A weighted reliability measure for phonetic transcription.
AB  - PURPOSE: The purpose of the present work is to describe and illustrate the
      utility of a new tool for assessment of transcription agreement. Traditional
      measures have not characterized overall transcription agreement with sufficient
      resolution, specifically because they have often treated all phonetic differences
      between segments in transcriptions as equivalent, thus constituting an unweighted
      approach to agreement assessment. The measure the authors have developed
      calculates a weighted transcription agreement value based on principles derived
      from widely accepted tenets of phonological theory. METHOD: To investigate the
      utility of the new measure, 8 coders transcribed samples of speech and infant
      vocalizations. Comparing the transcriptions through a computer-based
      implementation of the new weighted and the traditional unweighted measures, they
      investigated the scaling properties of both. RESULTS: The results illustrate
      better scaling with the weighted measure, in particular because the weighted
      measure is not subject to the floor effects that occur with the traditional
      measure when applied to samples that are difficult to transcribe. Furthermore,
      the new weighted measure shows orderly relations in degree of agreement across
      coded samples of early canonical-stage babbling, early meaningful speech in
      English, and 3 adult languages. CONCLUSIONS: The authors conclude that the
      weighted measure may provide improved foundations for research on phonetic
      transcription and for monitoring of transcription reliability.

PMID- 17197505
TI  - Response to Blomgren, Roy, Callister, and Merrill (2005).
AB  - PURPOSE: The purpose of this letter is to register concerns about a study
      reported by M. Blomgren, N. Roy, T. Callister, and R. Merrill (2005), entitled
      "Intensive Stuttering Modification Therapy: A Multidimentional Assessment of
      Treatment Outcomes." Concerns include questions about the description of the
      treatment, the duration of treatment time, and the results of the treatment.
      CONCLUSIONS: The treatment program did not inherently lend itself to clear
      description (would not be easily replicable), the participants did not improve
      their speech fluency, and the treatment time was extensive. One must take caution
      in the interpretation of the results given the concerns noted.

PMID- 17197507
TI  - Response to "Intensive stuttering modification therapy: a multidimensional
      assessment of treatment outcomes," by Blomgren, Roy, Callister, and Merrill
      (2005).
AB  - PURPOSE: M. Blomgren, N. Roy, T. Callister, and R. Merrill (2005) used a
      multidimensional approach to evaluate treatment efficacy for the Successful
      Stuttering Management Program. While the article acknowledged that the treatment
      program under evaluation does not target a reduction in stuttering frequency,
      Blomgren and colleagues concluded that the therapy "was ineffective in producing
      durable reductions of core stuttering behaviors, such as stuttering frequency and
      severity." In this response, it is suggested that Blomgren et al. used
      inappropriate treatment efficacy measures relative to the therapy program under
      evaluation, subsequently making the study's data difficult to interpret.
      CONCLUSION: It is suggested that stuttering treatment efficacy measures include
      client-reported treatment satisfaction data, efficacy measures relative to the
      goals and values of the therapy approach being evaluated, and data relative to
      the documented values and priorities of those within the stuttering population.

PMID- 17197509
TI  - The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse.
AB  - PURPOSE: To produce a mouse model of Leber hereditary optic neuropathy. METHODS:
      A mutant ND4 subunit made compatible with the universal genetic code and
      containing an arginine-to-histidine substitution at residue 340, or a synthetic
      normal human ND4 gene was delivered to the mouse visual system. The expression
      and effects of the mutant ND4 gene on the optic nerve and cultured retinal
      ganglion cells was assessed by magnetic resonance imaging, immunohistochemistry,
      and light and transmission electron microscopy. RESULTS: The ATPc mitochondrial
      targeting sequence directed the allotopically expressed mutant human R340H and
      wild-type ND4FLAG polypeptides into mitochondria. Expression of normal human ND4
      in murine mitochondria posed no ocular toxicity. In contrast, the mutant ND4
      disrupted mitochondrial cytoarchitecture, elevated reactive oxygen species,
      induced swelling of the optic nerve head, and induced apoptosis, with a
      progressive demise of ganglion cells in the retina and their axons comprising the
      optic nerve. CONCLUSIONS: Allotopic expression of the mutant human R340H ND4
      subunit of complex I replicated the hallmarks of human mitochondrial disease in
      the mouse. In contrast, ocular expression of the wild-type human ND4 subunit in
      lower mammals appears safe, suggesting that it may be useful for treatment of
      patients with Leber hereditary optic neuropathy.

PMID- 17197510
TI  - Relative axial myopia in Egr-1 (ZENK) knockout mice.
AB  - PURPOSE: Experiments in chickens have implicated the transcription factor ZENK
      (also known as Egr-1, NGFI-A, zif268, tis8, cef5, and Krox24) in the feedback
      mechanisms for visual control of axial eye growth and myopia development. ZENK is
      upregulated in retinal glucagon amacrine cells when axial eye growth is inhibited
      by positive spectacle lens wear and is downregulated when it is enhanced by
      negative spectacle lens wear, suggesting that ZENK may be linked to an inhibitory
      signal for axial eye growth. This study was undertaken to determine whether a Egr
      1(-/-) knockout mouse mutant, lacking ZENK completely, has longer eyes and more
      myopic refraction, than do Egr-1(+/)(-) heterozygous and Egr-1(+/+) wild-type
      mice with near-identical genetic backgrounds. METHODS: Eye growth and refractive
      development were tracked from day P28 to P98. Corneal radius of curvature was
      measured with infrared photokeratometry, refractive state with infrared
      photoretinoscopy, and ocular dimensions with low-coherence interferometry. As a
      functional vision test, grating acuity was determined in an automated optomotor
      task. The abundance of ZENK protein in the retina was quantified by
      immunohistochemistry. RESULTS: Egr-1 knockout mice had longer eyes and a relative
      myopic shift in refraction, with additional minor effects on anterior chamber
      depth and corneal radius of curvature. Paraxial schematic eye modeling suggested
      changes in the optics of the crystalline lens as well. With increasing age, the
      differences between mutant and wild-type mice declined, although the differences
      in refraction persisted over the observation period. Grating acuity was not
      affected by the lack of the Egr-1 protein during development. CONCLUSIONS:
      Although it has been shown that different mouse strains may have differently
      large eyes, the present study shows that a specific gene knockout can produce
      relative myopia, compared with the wild-type with near-identical genetic
      background. Further experiments are needed to determine whether the observed
      effects of Egr-1 deletion are due to changes in function within the retina or
      other ocular tissues or to changes of function in other systems that may affect
      ocular growth from outside the eye.

PMID- 17197512
TI  - Internalization is essential for the antiapoptotic effects of exogenous thymosin
      beta-4 on human corneal epithelial cells.
AB  - PURPOSE: Exogenous thymosin beta-4 (Tbeta(4)) has been shown to inhibit the
      apoptosis in nontransformed human corneal epithelial cells that is triggered by
      ethanol. The purpose of this study is to examine whether exogenous Tbeta(4)
      protects SV40-immortalized human corneal epithelial T (HCE-T) cells against the
      toxic effects of Fas ligand (FasL) and hydrogen peroxide (H(2)O(2)) and to
      elucidate its mechanism of action. METHODS: HCE-T cells were incubated without or
      with the recombinant histidine-tagged Tbeta(4) produced by Escherichia coli
      before the addition of FasL or H(2)O(2). Cell viability was determined by MTT or
      MTS assay, and activation of caspase-8, -9, and -3 was examined by colorimetric
      and fluorescent substrate cleavage assays. The internalization of exogenous
      Tbeta(4) in HCE-T cells was analyzed by immunofluorescence staining. Cytochalasin
      D, an actin depolymerization agent, was added to examine whether the actin
      cytoskeleton is involved in Tbeta(4) entry and whether the internalization of
      this peptide is crucial for its cytoprotection. RESULTS: The death of HCE-T cells
      induced by both FasL and H(2)O(2) was dramatically reduced by the recombinant
      Tbeta(4) pretreatment. Moreover, FasL-mediated activation of caspases-8 and -3 as
      well as H(2)O(2)-triggered stimulation of caspases-9 and -3 in these cells was
      abolished by preincubating them with the exogenous Tbeta(4). Of note,
      internalization of this G-actin-sequestering peptide into HCE-T cells was found
      to be essential in cell death prevention, in that disruption of the cellular
      entry of Tbeta(4) by cytochalasin D abrogated its cytoprotective effects.
      CONCLUSIONS: This is the first report to demonstrate that the internalization of
      exogenous Tbeta(4) is essential for its antiapoptotic activity in human corneal
      epithelial cells.

PMID- 17197511
TI  - Inhibition of cytokine signaling in human retinal endothelial cells through
      modification of caveolae/lipid rafts by docosahexaenoic acid.
AB  - PURPOSE: Docosahexaenoic acid (DHA(22:6,n3)) is the principal n3 polyunsaturated
      fatty acid (PUFA) in the retina. The authors previously demonstrated that
      DHA(22:6,n3) inhibited cytokine-induced adhesion molecule expression in primary
      human retinal vascular endothelial (hRVE) cells, the target tissue affected by
      diabetic retinopathy. Despite the importance of vascular inflammation in diabetic
      retinopathy, the mechanisms underlying anti-inflammatory effects of DHA(22:6,n3)
      in vascular endothelial cells are not understood. In this study the authors
      address the hypothesis that DHA(22:6,n3) acts through modifying lipid composition
      of caveolae/lipid rafts, thereby changing the outcome of important signaling
      events in these specialized plasma membrane microdomains. METHODS: hRVE cells
      were cultured in the presence or absence of DHA(22:6,n3). Isolated caveolae/lipid
      raft-enriched detergent-resistant membrane domains were prepared using sucrose
      gradient ultracentrifugation. Fatty acid composition and cholesterol content of
      caveolae/lipid rafts before and after treatment were measured by HPLC. The
      expression of Src family kinases was assayed by Western blotting and
      immunohistochemistry. RESULTS: Disruption of the caveolae/lipid raft structure
      with a cholesterol-depleting agent, methyl-cyclodextrin (MCD), diminished
      cytokine-induced signaling in hRVE cells. Growth of hRVE cells in media enriched
      in DHA(22:6,n3) resulted in significant incorporation of DHA(22:6,n3) into the
      major phospholipids of caveolae/lipid rafts, causing an increase in the
      unsaturation index in the membrane microdomain. DHA(22:6,n3) enrichment in the
      caveolae/raft was accompanied by a 70% depletion of cholesterol from
      caveolae/lipid rafts and displacement of the SFK, Fyn, and c-Yes from
      caveolae/lipid rafts. Adding water-soluble cholesterol to DHA(22:6,n3)-treated
      cells replenished cholesterol in caveolae/lipid rafts and reversed the effect of
      DHA(22:6,n3) on cytokine-induced signaling. CONCLUSIONS: Incorporation of
      DHA(22:6,n3) into fatty acyl chains of phospholipids in caveolae/lipid rafts,
      followed by cholesterol depletion and displacement of important signaling
      molecules, provides a potential mechanism for anti-inflammatory effect of
      DHA(22:6,n3) in hRVE cells.

PMID- 17197513
TI  - Identification of fatty acids and fatty acid amides in human meibomian gland
      secretions.
AB  - PURPOSE: The complex superficial lipid layer of the tear film functions to
      prevent evaporation and maintain tear stability. Although classes of lipids found
      in the tear film have been reported, individual lipid species are currently being
      studied with more sophisticated. METHODS: The purpose of this work was to show
      the identification of fatty acids and the fatty acid amides in human meibomian
      gland secretions by using electrospray mass spectrometry. methods. Human
      meibomian gland secretions (meibum) were analyzed by electrospray quadrupole time
      of-flight mass spectrometry (positive- and negative-ion mode). Accurate mass
      determination and collision-induced dissociation of meibum, and lipid standards
      were used to identify lipid species. RESULTS: Mass analysis of meibum in an
      acidic chloroform-methanol solution in positive-ion mode revealed a mass peak of
      m/z 282.3, which was identified as the protonated molecule of oleamide
      [C(18)H(35)NO+H](+). The high-resolution mass analysis of the m/z 282.2788 peak
      (oleamide) demonstrated a mass accuracy of 3.2 parts per million (ppm). Collision
      induced dissociation of this species from meibum, compared with an oleamide
      standard, confirmed its identification. Myristic, palmitic, stearic, and oleic
      free fatty acids were identified in a similar manner, as were the other fatty
      acid amides (myristamide, palmitamide, stearamide, and erucamide). CONCLUSIONS:
      The findings indicate that oleamide (cis-9-octadecenamide), an endogenous fatty
      acid primary amide, is a predominant component of meibum when examined by
      electrospray mass spectrometry. The novel finding of oleamide and other members
      of the fatty acid amide family in the tear film could lead to additional insights
      into the role of fatty acid amide activity in human biological systems and may
      indicate a new function for this lipid class of molecules in ocular surface
      signaling and/or in the maintenance of the complex tear film.

PMID- 17197515
TI  - Measurement of retinal vascular caliber: issues and alternatives to using the
      arteriole to venule ratio.
AB  - PURPOSE: The arteriole to venule ratio (AVR) is widely used in studies of the
      associations of retinal microvascular disease with systemic and ocular outcomes.
      This is a discussion of the limitations of AVR; a comparison of its predictive
      information with that of its components, arteriolar and venular caliber; and a
      description of a suggested alternative method of modeling arteriolar and venular
      calibers directly. METHODS: Data from the population-based Blue Mountains Eye
      Study were used to compare the predictive information in models using AVR with
      models using arteriolar and venular calibers directly. Determination was made of
      how the apparent relationship between vessel caliber and two systemic outcomes
      (blood pressure [BP] and white blood cell count [WBC]) was influenced by the
      choice of regression model. These findings were interpreted with reference to the
      known biological relationship among vessel calibers, BP, and WBC. RESULTS: Models
      using arteriolar and venular calibers directly had more predictive information
      than models using AVR. The apparent relationship of vessel caliber to BP and WBC
      differed substantially, depending on the model chosen. For example, after
      adjustment for age, sex, and other covariates, decreasing venular caliber was
      associated with higher systolic BP when modeled separately, but was associated
      with lower systolic BP when modeled simultaneously with arteriolar caliber.
      CONCLUSIONS: The findings suggest AVR provides less information with regards to
      predicting systemic outcomes than its two components. Modeling arteriolar and
      venular calibers separately could be biased by confounding, while modeling both
      simultaneously appears to provide unbiased, biologically plausible results. The
      use of this approach is recommended in future research relating retinal vascular
      caliber to systemic or ocular outcomes.

PMID- 17197516
TI  - Validity and repeatability of a new test for aniseikonia.
AB  - PURPOSE: The Aniseikonia Inspector 1.1 (AI) is a new software product to measure
      aniseikonia using red-green anaglyphs. The purpose of this study was to test
      whether the AI is a valid and reliable test. METHODS: There were two groups of
      sample subjects: one at risk of aniseikonia, with anisometropia greater than or
      equal to 1.00 D (n= 29), and a control group (n= 45). The validity was studied by
      comparing the measured aniseikonia with the aniseikonia simulated with size
      lenses. The reliability was estimated by the Bland-Altman statistical method.
      RESULTS: The results showed that the AI underestimated aniseikonia and that the
      underestimation was greater in the horizontal than in the vertical direction. The
      reliability was low, with biases that were clinically insignificant, but the 95%
      limits of agreement were around +/-2%. The behavior of the test was similar in
      both groups of subjects. CONCLUSIONS: The reliability of the AI is only moderate,
      and professionals are therefore warned to use the results of this test with
      caution.

PMID- 17197514
TI  - Light induces programmed cell death by activating multiple independent proteases
      in a cone photoreceptor cell line.
AB  - PURPOSE: Although the apoptotic death of photoreceptor cells in retinal
      degenerative disorders is well documented, the molecular mechanism is not
      understood. The objective of this study was to determine the molecular events
      leading to the death of photoreceptor cells. METHODS: An assay was developed
      wherein 661W cells, a cone photoreceptor cell line, were stressed with light and
      percentage of surviving cells was determined. The degree of cell death was
      established using the MTT assay. Western blot analysis was used to confirm the
      activation of multiple proteases. Amounts of retinaldehydes were determined by
      extraction and HPLC. RESULTS: 661W cells were more susceptible to light stress
      only in the presence of the chromophore 9-cis retinal for 4 hours. On exposure to
      light, 9-cis retinal was converted to all-trans retinal, which was found to be
      toxic to cells in the presence of light. However, all-trans retinol, which is the
      product of action by the enzyme retinol dehydrogenase on all-trans retinal, was
      not toxic. The sensitivity to light increased with serum deprivation. Light
      stress activated caspases, calpain 2, and cathepsin D independently and led to
      the demise of the cell. The mitochondria-dependent apoptotic pathway was also
      activated after the truncation of Bid, the pre-proapoptotic protein. Truncation
      of Bid led to the release of cytochrome c from the mitochondria and the
      activation of caspase 9. CONCLUSIONS: The activation of multiple proteases by
      light-induced stress is a relevant finding for studies conducted to investigate
      the use of pharmaceutical agents to retard or cure the loss of cone
      photoreceptors observed in age-related macular degeneration and other
      degenerative retinal diseases.

PMID- 17197517
TI  - Association of retinal vessel caliber to optic disc and cup diameters.
AB  - PURPOSE: To investigate whether optic disc size is related to retinal venule and
      arteriole diameters. METHODS: The population of Beaver Dam, Wisconsin, aged 43 to
      86 years were invited to participate in a baseline examination from 1988 to 1990.
      During this examination, photographs, centered on the optic discs, were taken
      after pupil dilation. Optic discs and cups were measured from stereoscopic
      photographs, whereas retinal vessel measurements were taken from a single
      digitized photograph. Central retinal vein and central retinal arterial
      equivalents were subsequently calculated. Data for 3887 right eyes are included
      in the analyses. RESULTS: Narrower retinal venules and arterioles were found in
      the smaller optic discs controlling for optic cup diameter as well as age,
      systolic and diastolic blood pressure, refraction, and sex. Central retinal
      artery equivalents ranged from 156.04 +/- 16.82 microm in the smallest optic disc
      category to 165.93 +/- 15.17 microm in the larger disc category (P < 0.001).
      Central retinal vein equivalents ranged from 228.93 +/- 21.26 microm in the
      smallest to 243.18 +/- 22.32 microm in the larger disc categories (P < 0.001).
      The significant reduction in retinal vessel diameters was only apparent for the
      smallest optic disc sizes. A reduction in retinal vessel diameters was less
      consistent and not significant for small optic cup sizes. CONCLUSIONS: Smallest
      optic discs were associated with smaller central retinal artery and central
      retinal vein diameters. This anatomic relationship may be useful as an additional
      associated indicator for nonarteritic anterior ischemic optic neuropathy as well
      as for retinal vascular events.

PMID- 17197518
TI  - Porcine model to compare real-time intraocular pressure during LASIK with a
      mechanical microkeratome and femtosecond laser.
AB  - PURPOSE: To compare real-time intraocular pressure (IOP) during laser in situ
      keratomileusis (LASIK) in porcine eyes using two types of microkeratomes.
      METHODS: An interventional, prospective study of two microkeratomes: a Moria 2
      (Moria group) and an IntraLase femtosecond laser (IntraLase Corp., Irvine, CA;
      IntraLase group). These devices were used to create lamellar corneal flaps in
      freshly enucleated porcine eyes. The IOP changes induced by the procedures were
      recorded with a reusable blood pressure transducer connected to the anterior
      chamber by direct cannulation. RESULTS: Seven porcine eyes were studied in each
      group. The IOP increased during the suctioning phase, reaching a mean of 122.52
      +/- 30.40 and 160.52 +/- 22.73 mm Hg during the cutting phase in the Moria group
      (the total time in this group was 36.42 +/- 7.48 seconds; suctioning required
      21.42 +/- 7.48 seconds and the cutting phase, 15 +/- 2.88 seconds). In the
      IntraLase group, the IOP reached 89.24 +/- 24.26 mm Hg during the suctioning
      phase and 119.33 +/- 15.88 mm Hg during the intrastromal laser application (the
      total time was 92.85 +/- 13.49 seconds; suctioning required 40.00 +/- 9.57
      seconds and the cutting phase 52.85 +/- 5.66 seconds). Both IOPs during both
      phases differed significantly between the two groups (P = 0.01 for all
      comparisons). CONCLUSIONS: Real-time IOP can be measured during LASIK using a
      transducer connected to the anterior chamber. The results showed a significant
      increase in IOP during the procedure in both groups, although with the IntraLase
      the IOP seemed to increase to a lesser extent than with the conventional
      mechanical microkeratome.

PMID- 17197519
TI  - Astigmatism in 12-year-old Australian children: comparisons with a 6-year-old
      population.
AB  - PURPOSE: To study the distributions of refractive (RA), corneal (CA), and
      internal astigmatism (IA) in 12-year-old Australian children and to explore
      differences from previous findings in 6-year-old children. METHODS: Eligible year
      7 students (2353/3144 [75.3%], median age, 12 years) from a random cluster sample
      of 21 high schools in Sydney, Australia, were examined by keratometry,
      cycloplegic autorefraction, and review of questionnaire data. RESULTS: Prevalence
      rates of RA, CA, and IA > or =1.0 D in right eyes were 6.7% (95% confidence
      interval [CI], 5.0-8.4), 26.6% (CI, 22.1-31.1), and 26.5% (CI, 22.9-30.0),
      respectively. RA was predominantly with-the-rule (WTR; 40.4%, CI, 32.6 to 48.2)
      and against-the-rule (ATR; 43.6%, CI, 35.7-51.5), CA was WTR (88.8%, CI, 86.3
      91.3), and IA was ATR (90.2%, CI, 87.8-92.6). The girls had significantly greater
      CA and IA prevalence, with greater ATR astigmatism and lower oblique IA than did
      the boys. The European white-Australian children had lower CA prevalence than did
      the East Asian-Australian children and higher IA prevalence than did the South
      Asian-Australian children. Ethnic differences in RA prevalence were not
      significant, when adjusted for confounders. RA was more frequently ATR in
      European white than in other ethnic groups. Compensation between CA and IA
      reduced the magnitude of RA. Comparison with the data on 6-year-old children
      revealed minimal differences for all astigmatic components. CONCLUSIONS: There
      was a relatively low prevalence of RA, due to compensation between CA and IA. The
      minimal differences in all components of astigmatism between the two age cohorts
      suggest that astigmatism is stable between ages 6 and 12 years, although this
      conclusion needs to be confirmed in longitudinal studies.

PMID- 17197520
TI  - Children unable to perform screening tests in vision in preschoolers study:
      proportion with ocular conditions and impact on measures of test accuracy.
AB  - PURPOSE: To examine the relative prevalence of ocular conditions among children
      who are unable to perform preschool vision screening tests and the impact on
      measures of screening test performance. METHODS: Trained nurse and lay screeners
      each administered a Lea Symbols visual acuity (VA) test (Good-Lite, Inc.,
      Steamwood, IL), Stereo Smile II test (Stereo Optical, Inc., Chicago, IL), and
      Retinomax Autorefractor (Right Manufacturing, Virginia Beach, VA), and SureSight
      Vision Screener (Welch Allyn, Inc., Skaneateles Falls, NY) examinations to 1475
      children who later received a comprehensive eye examination to identify
      amblyopia, strabismus, significant refractive error, and unexplained reduced VA.
      The outcomes of the examination for children for whom screeners were unable to
      obtain results (Unables) were compared to the outcomes of children who passed and
      children who failed each screening test. When estimating sensitivity,
      specificity, and positive and negative predictive values (PPV and NPV), Unables
      were classified as either screening failures or screening passers. RESULTS: Less
      than 2% of children were classified as Unables for each test. The percentage with
      an ocular condition was at least two times higher for Unables than for screening
      passers for six of the eight modes of screening (P < 0.05). Considering Unables
      as screening failures, rather than screening passers, increased the estimate of
      sensitivity by 1% to 3% (depending on test) and decreased the estimate of
      specificity by 0% to 2%; PPV decreased by 0% to 4% for most tests, whereas NPV
      increased by <1%. CONCLUSIONS: Preschool children who are unable to perform VIP
      screening tests are more likely to have vision disorders than are children who
      pass the tests. Because < or =2% of children were unable to do each test,
      referring these children for an eye examination had little impact on the PPV and
      NPV of the tests, as administered in VIP.

PMID- 17197521
TI  - Prevalence of lens opacities in North India: the INDEYE feasibility study.
AB  - PURPOSE: To obtain estimates of the prevalence of lens opacities in an Indian
      setting by using photographically acquired lens images. METHODS: In 11 randomly
      sampled villages from a rural district of Haryana, North India, 1443 people
      (median age 60 years), 52% women, were identified from enumeration of the > or
      =50-year age group; 87% attended an eye examination. Digital images of cortical
      and posterior subcapsular opacities and photographs of nuclear opacities were
      graded using the Lens Opacity Classification System (LOCS) II. The prevalence of
      opacities was based on a grade of 2 or higher in the worse eye for nuclear,
      cortical, or posterior subcapsular opacities. RESULTS: Of the participants, 1071
      people had gradable images; a further 163 had undergone surgery or had dense
      opacities. Nuclear opacities were the most common type, with an overall
      prevalence of 56.9% (95% CI, 53.0-60.6). Posterior subcapsular opacities occurred
      in 20.6% (95% CI, 17.9-25.8) and cortical opacities in 21.6% (95% CI, 17.9-25.8).
      Prevalence rose steeply with age for all opacities and was higher in the women
      than in the men for cortical opacities (P = 0.03). The prevalence of any type of
      lens opacity including surgical cases and dense opacities was 75.3% (95% CI, 71.4
      78.81). CONCLUSIONS: These results highlight the substantial excess of lens
      opacities in India compared with Western populations.

PMID- 17197522
TI  - Public health impact of neovascular age-related macular degeneration treatments
      extrapolated from visual acuity.
AB  - PURPOSE: To estimate the potential public health impact of treatment with new
      medications intended to preserve vision in patients with neovascular age-related
      macular degeneration (AMD). METHODS: A Markov model was used to simulate the
      natural history of AMD over the lifetime of patients with diagnosed neovascular
      AMD from clinical trials and epidemiologic surveys. It applied to a cohort of
      patients aged 75 years, with newly diagnosed neovascular AMD in one eye, whose
      visual acuity was 0.7 logMAR. Probabilities were calculated for the risk of AMD
      in the remaining eye and for premature mortality. Results of the model were
      expressed as the duration of low vision (worse eye VA>1.0 and better eye VA>0.7
      logMAR) and blindness (bilateral VA >1.0 logMAR). Health consequences of
      blindness and low vision were estimated for depression, hip fractures,
      institutionalization, and life expectancy. RESULTS: For AMD patients with a 50%
      probability of VA >1.0 logMAR at 1 year, in one eye, the probability of lifetime
      bilateral blindness was >47%. The patients would live approximately 7 years with
      monocular vision >1.0 logMAR and an additional 4 years with bilateral blindness
      and a >15% probability of depression due to AMD. Life expectancy was decreased by
      approximately 2 years, >90/1000 patients would sustain a new hip fracture, and
      1.5% of the patients would require institutional care for visual impairment due
      to AMD. To achieve a defined public health outcome (visual impairment and
      consequent comorbidity), it was necessary for the VA effectiveness of new
      treatments to increase in parallel with disease severity. CONCLUSIONS:
      Comorbidity related to visual impairment contributes significantly to the public
      health impact of AMD. Aggressive lesions need highly effective treatments. Models
      may be used to compare the public health impact of placebo-controlled clinical
      trial results.

PMID- 17197523
TI  - Circadian fluctuation of mean ocular perfusion pressure is a consistent risk
      factor for normal-tension glaucoma.
AB  - PURPOSE: To investigate systemic and ocular hemodynamic risk factors for
      glaucomatous damage in eyes with normal tension glaucoma (NTG). METHODS: Each
      patient with diagnosed NTG underwent 24-hour monitoring of intraocular pressure
      (IOP) and blood pressure (BP), scanning laser polarimetry (GDx-VCC), and a
      Humphrey visual field (HVF) examination. Multivariate regression models were used
      to evaluate potential risk factors: age, spherical equivalent, central corneal
      thickness (CCT), mean/peak in-hospital IOP, circadian IOP fluctuation, average
      mean arterial pressure (MAP), circadian MAP fluctuation, and circadian
      fluctuation of mean ocular perfusion pressure (MOPP). Functional outcome
      variables for glaucomatous damage were mean deviation (MD), pattern SD (PSD), and
      Advanced Glaucoma Intervention Study (AGIS) score. Anatomic outcome variables
      were TSNIT (temporal, superior, nasal, inferior, and temporal) average, superior
      average, inferior average, and nerve fiber indicator (NFI) on GDx-VCC. RESULTS:
      One hundred thirteen eyes of 113 patients met the inclusion criteria. In the
      multivariate regression models, larger circadian MOPP fluctuation was
      significantly associated with decreased MD, increased PSD, and increased AGIS
      score among functional outcome variables and with reduced TSNIT average, reduced
      inferior average, and increased NFI among anatomic outcome variables. Larger MAP
      fluctuation was associated with decreased MD, increased PSD, reduced TSNIT
      average, reduced inferior average, and increased NFI. CCT was not associated with
      any outcome variable. CONCLUSIONS: Of the functional and anatomic outcome
      variables, circadian MOPP fluctuation was the most consistent clinical risk
      factor for glaucoma severity in eyes with NTG. This finding may suggest an
      etiology of NTG as a chronic ischemic end organ disease.

PMID- 17197524
TI  - The influence of eyelid morphology on normal corneal shape.
AB  - PURPOSE: To investigate associations between the topography of the cornea and the
      morphology of the eyelids in a population of young adult subjects with a range of
      refractive errors. METHODS: Corneal topography data and digital images of the
      anterior eye were acquired for 100 young adult subjects. The corneal topography
      data and palpebral fissure images were analyzed to determine a range of
      parameters describing the shape of the cornea and the morphology of the palpebral
      fissure. Correlation analysis was carried out to investigate for significant
      associations between the parameters describing the topography of the cornea and
      the parameters describing the morphology of the palpebral fissure. RESULTS: A
      number of highly significant correlations were found between the best-fitting
      corneal spherocylinder and the eyelid morphology parameters. The corneal best-fit
      sphere (M) was significantly correlated with the horizontal palpebral fissure
      width (r = -0.428; P < 0.001). Corneal astigmatism power vector J45 was
      significantly correlated with the angle of the palpebral fissure (r = 0.392; P <
      0.001). The axis of corneal astigmatism was also found to be significantly
      correlated with the angle of the palpebral fissure (r = 0.317; P = 0.005).
      CONCLUSIONS: A number of significant associations exist between the corneal
      spherocylinder and the morphology of the eyelids in a normal adult population.

PMID- 17197525
TI  - Thrombin inhibits intercellular calcium wave propagation in corneal endothelial
      cells by modulation of hemichannels and gap junctions.
AB  - PURPOSE: Thrombin, a serine protease, breaks down the barrier integrity of
      corneal endothelial cells by phosphorylation of the regulatory light chain of
      myosin II (myosin light chain; MLC), which induces contractility of the actin
      cytoskeleton. This study was undertaken to investigate the effect of thrombin on
      gap junctional (GJIC) and paracrine (PIC) intercellular communication in cultured
      bovine corneal endothelial cells (BCECs). METHODS: An intercellular Ca(2+) wave,
      a form of cell-cell communication, was elicited by applying a mechanical stimulus
      to a single cell in a confluent monolayer. Changes in [Ca(2+)](i) were imaged by
      fluorescence microscopy with a fluorescent calcium indicator, and the images were
      used to calculate the area reached by the Ca(2+) wave (active area). GJIC was
      assessed by fluorescence recovery after photobleaching (FRAP). Activity of
      hemichannels was assayed by lucifer yellow (LY) uptake and also by adenosine
      triphosphate (ATP) release by using the luciferin-luciferase technique. RESULTS:
      RT-PCR showed transcripts for PAR-1 and -2 receptors, but not for PAR-4
      receptors. Immunocytochemistry showed thrombin-sensitive PAR receptors as well as
      trypsin-sensitive PAR-2 receptors. Both thrombin and the selective PAR-1 agonist
      TRAP-6 reduced the active area of the Ca(2+) wave. These agents also reduced the
      fluorescence recovery in FRAP experiments. The effect of thrombin on the Ca(2+)
      wave was inhibited by a peptide antagonist of PAR-1, but not by a PAR-4
      antagonist. Pretreatment with ML-7 (an MLCK inhibitor), Y-27632 (a Rho kinase
      inhibitor) or chelerythrine (a PKC inhibitor) prevented the effect of thrombin on
      the Ca(2+) wave. Activation of PAR-1 did not affect the Ca(2+) wave propagation
      in cells pretreated with Gap26, which blocks hemichannels. However, PAR-1
      activation decreased the active area in cells pretreated with Gap27, which
      inhibits gap junctions. Thrombin abolished enhancement of the Ca(2+) wave
      propagation by ARL-67156 (inhibitor of ecto-ATPases). The effect of the PAR-1
      agonists on the Ca(2+) wave was not detectable in cells pretreated with exogenous
      apyrases. CONCLUSIONS: Thrombin inhibits intercellular Ca(2+) wave propagation in
      BCECs. This effect is due to activation of PAR-1 receptors and involves MLC
      phosphorylation by MLCK-, PKC- and Rho kinase-sensitive pathways. Thrombin mainly
      inhibits the ATP-mediated PIC pathway, and also reduces GJIC to a lesser extent.

PMID- 17197526
TI  - Corneal activation of prothrombin to form thrombin, independent of vascular
      injury.
AB  - PURPOSE: Two major functions of thrombin observed in the cornea are activation of
      thrombin-sensitive, proteinase-activated receptors and cleavage of fibrinogen to
      fibrin. The purpose of this study was to determine whether the normal human
      cornea itself is competent to convert prothrombin to thrombin and synthesizes the
      mRNA for the proteins required. METHODS: Human corneas were processed for
      immunolocalization studies or separated into epithelial, stromal, and endothelial
      layers for proteins and RNA isolation. The protein extracts were used for Western
      blots, prothrombin time, and activated partial thromboplastin time assays and
      fibrinopeptide A generation tests. RNA was used for RT-PCR. Apoptosis of cultured
      human corneal cells was induced with sodium nitroprusside or camptothecin and
      activation of prothrombin tested. RESULTS: Prothrombin and its mRNA were present
      in all three layers of human donor cornea. It was found to be associated with the
      cells and the extracellular matrix at similar levels across the cornea. With
      corneal stromal extracts, activation of either the intrinsic or extrinsic
      coagulation pathways resulted in thrombin activation and fibrin formation with
      fibrinopeptide A release. Detection of key components of the coagulation cascades
      confirmed noninjured human corneas contain factors required for prothrombin
      activation. In addition, mRNAs for representative factors and inhibitors were
      detected by RT-PCR and confirmed by sequencing. Apoptotic corneal stromal cells
      provide a surface for prothrombin activation. CONCLUSIONS: These studies suggest
      that the normal avascular human cornea contains and synthesizes the components
      required for thrombin generation and that this process does not depend on a
      breech in the limbal vascular endothelium.

PMID- 17197527
TI  - The phenotype of limbal epithelial stem cells.
AB  - PURPOSE: The purpose of this study was to identify phenotypic markers of human
      limbal stem cells in fetal and adult corneas. METHODS: RNA from microscopically
      dissected superficial limbal and central fetal (18 weeks) corneas was amplified
      and used to generate P(32)-labeled, reverse-transcribed antisense RNA that was
      linearly amplified and hybridized to a focused stem cell cDNA microarray.
      Differential gene expression of fetal limbus was compared with the expression of
      central cornea. Microarray differential expression experiments were performed on
      P63-expressing primary cultured limbal epithelial cells (passage 1; Pa1) and
      primary cells passaged 5 times (Pa5). Semiquantitative RT-PCR assay and
      immunohistochemistry were performed on fetal and adult corneas and cultured
      primary limbal epithelial cells, to confirm the results of the microarray
      experiments. Slow-cycling (pulsed bromodeoxyuridine label-retaining) limbal
      epithelium in corneal organ culture was studied for the expression of four
      selected upregulated limbal genes. RESULTS: Of the 266 genes tested, 33 were
      differentially overexpressed (more than twofold) in the fetal limbus (compared
      with central cornea) and primary cultured limbal epithelium compared with primary
      cells after 5 passages. Cytokeratin 15 (CK15) and cytokeratin 14 (CK14) are
      expressed in limbal basal epithelium and P-cadherin (CDH3) and Wnt-4 expression
      was restricted to basal and immediate parabasal limbal epithelium of both the
      adult and fetal corneas). Bromodeoxyuridine label retaining epithelium in corneal
      organ culture (slow-cycling cells) expressed the four selected limbal upregulated
      genes. CONCLUSIONS: For the first time, a focused stem cell pathway microarray
      analysis has been performed on fetal cornea and cultured limbal explant
      epithelium. CK15, CK14, CDH3, and Wnt-4 are expressed in the basal limbal
      epithelial cells.

PMID- 17197528
TI  - Light-scattering and ultrastructure of healed penetrating corneal wounds.
AB  - PURPOSE: To investigate quantitatively for the first time the relationship
      between light-scattering and ultrastructure of semitransparent scars resulting
      from penetrating wounds in rabbit cornea. METHODS: Penetrating wounds, 2 mm in
      diameter, were made in the central cornea and allowed to heal for 3.6 to 4.5
      years at which time the rabbits were killed. The scar and cornea thickness
      outside the scar were measured using ultrasonic pachymetry. Corneas were excised
      immediately and their transmissivity was measured from 400 to 700 nm. The tissue
      was then prepared for transmission electron microscopy. Transmission electron
      micrographs (TEMs) were analyzed to determine fibril positions and radii.
      Scattering was calculated using the direct summation of fields (DSF) METHOD:
      RESULTS: Scar thickness averaged 0.26 +/- 0.04 mm, and the scars were flat.
      Thickness outside the scars averaged 0.40 +/- 0.04 mm. Three scars were
      moderately transparent, five were less transparent, and one was much less
      transparent. The wavelength dependence of the measured total scattering cross-
      section was indicative of the presence of voids (lakes) in the collagen fibril
      distribution, and lakes were evident in the TEMs. The images showed enlarged
      fibrils and some showed bimodal distributions of fibril diameters. Calculated
      scattering was characteristic of that expected from regions containing lakes-a
      finding consistent with the scattering measurements. CONCLUSIONS: Despite the
      long healing time, these scars remained highly scattering. A combination of
      lakes, disordered fibril distributions, and a significant population of enlarged
      fibrils can explain the scattering. A possible cellular contribution cannot be
      ruled out.

PMID- 17197529
TI  - Objective measurement of backscattered light from the anterior and posterior
      cornea in vivo.
AB  - PURPOSE: To develop an objective and repeatable method of measuring corneal
      backscattered light from different depths of the cornea in vivo. METHODS: A
      modified slit lamp ("scatterometer"), with a video camera and synchronous white
      strobe light, was used to capture images of a 0.1-mm-wide slit beam through the
      cornea. Image analysis software was developed to measure backscatter from
      digitized high-magnification images of 82 normal corneas of 41 subjects. Forty
      eyes of 20 of the same subjects were examined again after 1 month. Mean
      backscatter from the anterior, middle, and posterior thirds of the cornea was
      compared between repeated measurements, and expressed in arbitrary scatter units
      (SU). RESULTS: Backscatter in the anterior third of the cornea was 451 +/- 42 SU
      (mean +/- SD, n = 82), from the middle third was 274 +/- 29 SU (n = 82), and from
      the posterior third was 242 +/- 28 SU (n = 82). The difference in backscatter
      measured a month apart was 5 +/- 27 SU (P = 0.34), 2 +/- 17 SU (P = 0.42), and 0
      +/- 15 SU (P = 0.95) in the anterior, middle, and posterior thirds of the cornea,
      respectively. Minimum detectable differences between measurements were 12, 8, and
      7 SU in the anterior, middle and posterior thirds, respectively (alpha = 0.05,
      beta = 0.20, n = 40). CONCLUSIONS: Backscatter can be measured at different
      depths of the cornea from high-magnification digitized images of a narrow slit
      beam through the cornea. The method is objective and repeatable and can be
      applied in prospective studies of deep and posterior lamellar keratoplasty.

PMID- 17197530
TI  - Relation between corneal innervation with confocal microscopy and corneal
      sensitivity with noncontact esthesiometry in patients with dry eye.
AB  - PURPOSE: An alteration in corneal innervation has been described in dry eye
      associated with diabetes mellitus, contact lens use, and LASIK. The purpose of
      this study was to evaluate whether dry eye not related to Sjogren's syndrome
      (NSDE) and dry eye related to primary Sjogren's syndrome (PSDE) are associated
      with an alteration of the corneal nerves and sensation. METHODS: Twenty-one
      patients with dry eye (10 NSDE and 11 PSDE) and 20 healthy volunteers were
      studied. Healthy volunteers were divided into two groups: one younger than 60
      years (N<60) and the other 60 years of age or older (N> or =60). The study of the
      epithelium, stroma, and subbasal corneal nerves was performed with a confocal
      microscope. Mechanical, chemical, and thermal sensation was evaluated using the
      Belmonte noncontact esthesiometer. RESULTS: A statistically significant decrease
      in the number and density of subbasal nerves (P < 0.0001) and the density of
      superficial epithelial cells (P < 0.0001) was observed in dry eyes. The number
      and density of subbasal nerves was higher in the N<60 group. A significant
      decrease was found with respect to mechanical, chemical, and thermal sensitivity
      (P < 0.0001). Sensibility was better in the healthy eyes. A strong correlation
      was found between the density of superficial epithelial cells and the nerves and
      between the number and density of subbasal nerves and sensation (P < 0.001).
      CONCLUSIONS: The use of confocal microscopy and noncontact esthesiometry allow
      the detection of the presence of corneal neuropathy in patients with dry eye.

PMID- 17197531
TI  - Comparative effects of the nonsteroidal anti-inflammatory drug nepafenac on
      corneal sensory nerve fibers responding to chemical irritation.
AB  - PURPOSE: To compare the corneal analgesic efficacy of the nonsteroidal anti
      inflammatory drugs (NSAIDs) nepafenac, diclofenac, and ketorolac, and to evaluate
      the possibility that their inhibitory effects on corneal polymodal nociceptor
      fiber activity are partly mediated by a decrease in sodium currents. METHODS:
      Corneal sensory afferent units were recorded in the anesthetized cat. The
      response of thin myelinated polymodal nociceptor fibers to mechanical and acidic
      stimulation (98.5% CO(2)) was recorded before and at various times after topical
      application of the vehicle or of nepafenac 0.1% (Nevanac; Alcon Laboratories,
      Ltd., Fort Worth, TX), diclofenac 0.1% (Voltaren; Novartis, Basel, Switzerland),
      and ketorolac 0.4% (Acular LS; Allergan, Irvine, CA). Voltage-clamp recordings
      were performed in cultured trigeminal ganglion neurons. RESULTS: Nepafenac,
      diclofenac, and ketorolac reduced the mean frequency of the impulse response
      evoked by repeated CO(2) stimuli in polymodal nociceptor fibers. The progressive
      increase in ongoing activity, observed in vehicle-treated eyes after repeated
      acidic stimulation was also prevented. Nepafenac exhibited a more rapid and a
      slightly more pronounced effect on spontaneous and CO(2)-evoked activity than did
      diclofenac and ketorolac and did not affect the responsiveness of corneal
      mechanonociceptor or cold receptor fibers. In cultured mice trigeminal ganglion
      neurons, diclofenac significantly suppressed sodium currents, whereas nepafenac
      or its metabolite, amfenac, exhibited only minimal inhibitory effects.
      CONCLUSIONS: The inhibition of polymodal nociceptor activity by nepafenac, a weak
      inhibitor of cyclooxygenase, is most likely due to its greater lipophilicity
      compared with diclofenac and ketorolac, leading to a rapid saturation of the
      corneal epithelium where nociceptor terminals are located. In contrast to
      diclofenac, nepafenac does not exhibit local anesthetic effects.

PMID- 17197532
TI  - Two pedigrees segregating Duane's retraction syndrome as a dominant trait map to
      the DURS2 genetic locus.
AB  - PURPOSE: The genetic bases of Duane's retraction syndrome (DRS) were investigated
      to determine its molecular etiologies. In prior studies, the transcription
      factors SALL4 and HOXA1 were identified as the genes mutated in DRS with radial
      anomalies, and in DRS with deafness, vascular anomalies, and cognitive deficits,
      respectively. Less is known, however, about the genetic etiology of DRS when it
      occurs in isolation, and only one genetic locus for isolated DRS, the DURS2 locus
      on chromosome 2, has been mapped to date. Toward the goal of identifying the
      DURS2 gene, two pedigrees have been ascertained that segregate DRS as a dominant
      trait. METHODS: Members of two large dominant DRS pedigrees were enrolled in an
      ongoing study of the genetic basis of the congenital cranial dysinnervation
      disorders, and linkage analysis was conducted to determine whether their DRS
      phenotype maps to the DURS2 locus. RESULTS: By haplotype analysis, the DRS
      phenotype in each family cosegregates with markers spanning the DURS2 region.
      Linkage analysis reveals maximum lod scores >2, establishing that the DRS
      phenotype in these two pedigrees maps to the DURS2 locus. CONCLUSIONS: These two
      pedigrees double the published pedigrees known to map to the DURS2 locus and can
      thus contribute toward the search for the DURS2 gene. The affected members
      represent a genetically defined population of DURS2-linked DRS individuals, and
      hence studies of their clinical and structural features can enhance understanding
      of the DURS2 phenotype, as described in the companion paper.

PMID- 17197533
TI  - Magnetic resonance imaging evidence for widespread orbital dysinnervation in
      dominant Duane's retraction syndrome linked to the DURS2 locus.
AB  - PURPOSE: High-resolution, multipositional magnetic resonance imaging (MRI) was
      used to demonstrate extraocular muscles (EOMs) and associated motor nerves in
      Duane retraction syndrome (DRS) linked to the DURS2 locus on chromosome 2.
      METHODS: Five male and three female affected members of two autosomal dominant
      DURS2 pedigrees were enrolled in the study. Coronal T(1)-weighted MRI of the
      orbits was obtained in multiple gaze positions, as well as with heavy T(2)
      weighting in the plane of the cranial nerves. MRI findings were correlated with
      motility. RESULTS: All subjects had unilateral or bilateral limitation of
      abduction, or of both abduction and adduction, with palpebral fissure narrowing
      and globe retraction in adduction. Orbital motor nerves were typically small,
      with the abducens nerve (cranial nerve [CN]6) often nondetectable. Lateral rectus
      (LR) muscles were structurally abnormal in seven subjects, with structural and
      motility evidence of oculomotor nerve (CN3) innervation from vertical rectus EOMs
      leading to A or V patterns of strabismus in three cases. Four cases had superior
      oblique, two cases superior rectus, and one case levator EOM hypoplasia. Only the
      medial and inferior rectus and inferior oblique EOMs were spared. Two cases had
      small CN3s. CONCLUSIONS: DRS linked to the DURS2 locus is associated with
      bilateral abnormalities of many orbital motor nerves, and structural
      abnormalities of all EOMs except those innervated by the inferior division of
      CN3. The LR may be coinnervated by CN3 branches normally destined for any other
      rectus EOMs. Therefore, DURS2-linked DRS is a diffuse congenital cranial
      dysinnervation disorder involving but not limited to CN6.

PMID- 17197534
TI  - Blink recovery in patients with Bell's palsy: a neurophysiological and behavioral
      longitudinal study.
AB  - PURPOSE: To examine the recovery process of blinking in a longitudinal study of
      nine patients severely affected by Bell's palsy. METHODS: Kinematics of bilateral
      eyelid and eye movements and concomitant orbicularis oculi activity during
      voluntary blinking and air-puff- and acoustic-click-induced reflex blinking were
      determined by using the magnetic search coil technique and electromyographic
      recording of the orbicularis oculi muscle (OO-EMG). RESULTS: In the first 3
      months of absence of OO-EMG activity, reduced eyelid and eye movement of the
      palsied eyelid were observed during all types of blinking. First OO-EMG activity
      was determined 3 months after onset of the affliction. After 1 year, OO-EMG
      activity was normalized and showed values similar to those on the nonpalsied
      side. Clinically, eyelid movements were normal after 1 year, although
      corresponding maximum amplitudes and corresponding velocities were two times
      smaller, expressed in reduced eyelid motility. Directions of eye movement during
      reflex blinking were normal after 1 year, although maximum amplitudes were
      smaller on the palsied side. Eye movements during voluntary blinking remained
      impaired. A simultaneous horizontal upward shift of both eyes in the same
      direction was recorded throughout the study. CONCLUSIONS: Although OO-EMG
      activity on the palsied side was normalized 1 year after onset of the affliction,
      the accompanying eyelid movements and their maximum amplitudes and velocities
      remained smaller throughout the study. The consistent impairment of eye movements
      in voluntary blinking during the study and reduced motility of eyelid movements
      indicates that higher brain structures, which modify eyelid and eye movement
      control during blinking, may be altered by the affliction.

PMID- 17197535
TI  - The effects of study design and spectrum bias on the evaluation of diagnostic
      accuracy of confocal scanning laser ophthalmoscopy in glaucoma.
AB  - PURPOSE: To assess the effects of study design and spectrum bias on the
      evaluation of diagnostic accuracy of confocal scanning laser ophthalmoscopy
      (CSLO) in glaucoma. METHODS: Analysis 1 included 67 eyes with glaucomatous visual
      field loss and 56 eyes of normal volunteers. Estimates of diagnostic accuracy in
      this analysis were compared to those obtained from analysis 2, which included a
      cohort of patients with suspected glaucoma, but without visual field loss at the
      time of CSLO imaging. For analysis 2, 40 eyes with progressive glaucomatous optic
      disc change were included in the glaucoma group and 43 eyes without any evidence
      of progressive damage to the optic nerve that were observed untreated for an
      average time of 9.01 +/- 3.09 years were included in the normal group. Areas
      under the receiver operating characteristic (ROC) curves (AUC) were used to
      evaluate diagnostic accuracy of CSLO parameters. RESULTS: There was a
      statistically significant difference between the performance of the parameter
      with largest AUC, discriminant function Bathija, in analysis 1 (AUC = 0.91)
      compared with its performance in analysis 2 (AUC = 0.71; P = 0.002). For the
      contour-line-independent parameter glaucoma probability score, a statistically
      significant difference was also observed in the performance obtained in analysis
      1 (AUC = 0.89) compared with analysis 2 (AUC = 0.65; P < 0.001). CONCLUSIONS:
      Estimates of diagnostic accuracy of CSLO in glaucoma can be largely different
      depending on the population studied and the reference standard used to define
      disease. Diagnostic accuracy estimates obtained from case-control studies
      including well-defined groups of subjects with or without disease may not be
      applicable to the clinically relevant population.

PMID- 17197536
TI  - The effect of atypical birefringence patterns on glaucoma detection using
      scanning laser polarimetry with variable corneal compensation.
AB  - PURPOSE: The purpose of this study was to investigate the effect of the presence
      of atypical birefringence patterns, as measured by the typical scan score (TSS),
      on the diagnostic accuracy of a scanning laser polarimeter (the GDx VCC; Carl
      Zeiss Meditec, Inc., Dublin, CA) assessed by receiver operating characteristic
      (ROC) curves for discriminating between glaucoma and healthy eyes. METHODS: Two
      hundred thirty-three glaucomatous eyes (repeatable abnormal visual fields by
      pattern standard deviation [PSD] and/or glaucoma hemifield test [GHT]) from 153
      patients with glaucoma and 104 eyes from 71 healthy participants enrolled in the
      UCSD Diagnostic Innovations in Glaucoma Study (DIGS) were imaged using the GDx
      VCC. An ROC regression model was used to evaluate the influence of the covariates
      TSS; disease severity, defined as standard automated perimetry (SAP) mean
      deviation [MD]; and age in years on the diagnostic accuracy of the GDx parameters
      nerve fiber indicator [NFI], TSNIT (temporal, superior, nasal, inferior,
      temporal) average thickness, superior average thickness, inferior average
      thickness, and TSNIT standard deviation. Areas under the ROC curve were
      calculated for specific levels of the covariates according to the results
      provided by the model. RESULTS: TSS and SAP MD significantly affected the
      diagnostic accuracy of each investigated GDx VCC parameter. Low TSSs, indicating
      the presence of atypical scans, were associated with decreased accuracy. For NFI,
      ROC curve areas ranged from 0.749 (when TSS = 20) to 0.904 (when TSS = 100). A
      similar influence of TSS was found for other parameters. In addition, diagnostic
      accuracy increased with increasing disease severity. For instance, for NFI, ROC
      curve areas ranged from 0.853 (when SAP MD = -3) to 0.954 (when SAP MD = -15).
      CONCLUSIONS: The diagnostic accuracy of GDx VCC parameters is affected by disease
      severity and is adversely affected by the presence of atypical retardation
      patterns (i.e., decreasing TSS). GDx VCC scans with atypical scan patterns should
      be interpreted with caution when used in clinical practice.

PMID- 17197537
TI  - Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma
      patients with FOXC1 and PITX2 mutations.
AB  - PURPOSE: To improve the understanding of Axenfeld-Rieger Malformation (ARM)
      associated glaucoma and to determine the best glaucoma treatment for patients
      with ARM who have known genetic defects in FOXC1 or PITX2. METHODS: Clinical data
      were collected from patients with diagnosed ARM, in whom we had previously
      identified disease-causing mutations in either the FOXC1 or PITX2 genes, by
      examination of patient records and use of clinical questionnaires. One hundred
      twenty-six patients with ARM, representing 20 different probands, with FOXC1 and
      PITX2 alterations were included in the study. RESULTS: ARM-associated glaucoma is
      a bilateral anterior segment dysgenesis disease that affects males and females
      equally. Seventy-five percent of the patients with ARM who participated in this
      study had glaucoma that had developed in adolescence or early adulthood. Of note,
      the patients with nonocular findings were more likely to have PITX2 defects than
      FOXC1 defects. Glaucoma in only 18% of patients with either PITX2 or FOXC1
      genetic defects responded to medical or surgical treatment (used solely or in
      combination). CONCLUSIONS: Patients with FOXC1 mutations have the mildest
      prognosis for glaucoma development, whereas patients with PITX2 defects and
      patients with FOXC1 duplication have a more severe prognosis for glaucoma
      development than do patients with FOXC1 mutations. In the present study, current
      medical therapies do not successfully lower intraocular pressure or prevent
      progression of glaucoma in patients with ARM who have FOXC1 or PITX2 alterations.
      This clinical study also provides useful diagnostic criteria to identify the gene
      responsible for ARM.

PMID- 17197538
TI  - The optic nerve head in myocilin glaucoma.
AB  - PURPOSE: Approximately 1 in 30 unselected patients with open-angle glaucoma (OAG)
      have a mutation in the myocilin gene. The purpose of this study was to describe
      the morphologic features of the optic nerve head (ONH) in myocilin glaucoma.
      METHODS: A case-control design was adopted. Sixty-six patients heterozygous for a
      range of myocilin mutation (cases) were matched in disease severity to 105
      patients with OAG known not to have a myocilin mutation (controls), using visual
      field findings. Quantifiable analysis of the ONH was undertaken of stereoscopic
      photographs, by using custom software with a z-screen. Subjective grading of the
      cup depth, lamina cribrosa pore shape and orientation, and the slope of the
      neuroretinal rim was performed by an examiner masked to the subject's mutation
      status. Mutation screening was conducted using either direct sequencing or single
      stranded conformation polymorphism analysis. RESULTS: Patients with a myocilin
      mutation had glaucoma diagnosed earlier (P < 0.001) and had higher maximum
      recorded intraocular pressures (P < 0.001) than did the control OAG subjects.
      There was no significant (P > 0.05) difference in global disc area, global
      neuroretinal rim area, alpha-parapapillary atrophy, beta-parapapillary atrophy,
      slope of neuroretinal rim, or visible lamina cribrosa morphology between myocilin
      mutation carriers and patients with nonmyocilin glaucoma. Disc hemorrhages were
      identified more frequently in those without mutations (14/209 vs. 1/129), though
      this was not significant after correction for multiple hypothesis testing.
      CONCLUSIONS: No major structural or morphologic difference of the ONH was
      detected in pooled data from subjects who had myocilin mutations compared with
      data from individuals with nonmyocilin glaucoma.

PMID- 17197539
TI  - Rule extraction for glaucoma detection with summary data from StratusOCT.
AB  - PURPOSE: To extract and induce rules of association for differentiating between
      normal and glaucomatous eyes based on the quantitative assessment of summary data
      reports from the StratusOCT (optical coherence tomography; Carl Zeiss Meditec,
      Inc., Dublin, CA) in a Taiwan Chinese population. METHODS: One randomly selected
      eye of each of the 64 patients with glaucoma and each of the 71 normal subjects
      was included in the study. Measurements of glaucoma variables (retinal nerve
      fiber layer thickness and optic nerve head analysis results) were obtained with
      the StratusOCT. A self-organizing map and decision tree were applied to extract
      features and determine rules of association for glaucoma detection. RESULTS: The
      average visual field mean deviation was -0.55 +/- 0.57 dB in the normal group and
      -4.30 +/- 3.32 dB in the glaucoma group. Vertical cup-to-disc (C/D) ratio and
      inferior quadrant thickness were extracted from the decision tree, and three
      association rules were determined for glaucoma detection. CONCLUSIONS: The
      precise rules of association induced by a novel application of the decision tree
      may enhance glaucoma detection.

PMID- 17197540
TI  - Monitoring glaucomatous visual field progression: the effect of a novel spatial
      filter.
AB  - PURPOSE: To assess the impact of a novel visual field spatial filtering technique
      on the detection of glaucomatous progression. METHODS: One hundred ninety-eight
      ocular hypertensive (OHT) and 21 control subjects were examined prospectively
      (1994-2001) with regular full-threshold Humphrey visual field (VF) testing. VF
      progression was assessed by point-wise linear regression (PLR) of
      sensitivity/time in Progressor for Windows software modified to include a novel
      spatial filter. Standard progression criteria (slope > -1 dB/year, P < 0.01) were
      applied to both "raw" (unfiltered) and "filtered" VF series. Three-omitting
      confirmatory VF criteria were also applied to unfiltered VF series. Specificity
      was estimated as the proportion of progressing control subjects and as the
      proportion of significantly improving subjects (both OHT and control) at the end
      of the study period. RESULTS: Applying standard PLR, specificity was estimated at
      91.8% to 97.5% using unfiltered standard PLR, compared with 93.5% to 98.4% using
      filtered standard PLR and 95.4% to 99.3% using unfiltered three-omitting PLR. The
      rate of identified VF progression in the OHT cohort was 32.3% with unfiltered
      standard PLR, 28.7% with filtered standard PLR, and 18.6% with unfiltered three
      omitting PLR. There was no significant difference in time to detected progression
      between filtered and unfiltered standard PLR. CONCLUSIONS: The use of
      confirmatory tests resulted in improved specificity using unfiltered data;
      however, application of the spatial filter resulted in similar specificity but
      with a higher rate of detected progression. This filter may therefore be useful
      in the monitoring of glaucomatous progression as it may reduce the dependence on
      confirmatory testing, although it has yet to be applied to longitudinal SITA
      data.

PMID- 17197541
TI  - Relationship between visual field sensitivity and retinal nerve fiber layer
      thickness as measured by optical coherence tomography.
AB  - PURPOSE: To evaluate the strength and pattern of the relationship between visual
      field (VF) sensitivity and retinal nerve fiber layer (RNFL) thickness as measured
      by StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA). METHODS: Three hundred
      eleven subjects--45 normal, 102 with preperimetric glaucoma (PPG), and 164 with
      primary open-angle glaucoma (POAG)--were enrolled in this cross-sectional study.
      The relationship between RNFL thickness and VF sensitivity, expressed as mean
      deviation (MD) and mean sensitivity (MS), were evaluated with linear and
      nonlinear regression models, and the coefficient of determination (R(2)) was
      calculated. The association between RNFL/VF was described by bivariate Pearson
      correlation coefficients. RESULTS: The correlation of RNFL and the VF parameters
      MS and MD in normal and PPG eyes was not significant. In POAG eyes, RNFL and both
      MS (r = 0.733) and MD (r = 0.718) correlated significantly. Linear regression
      plots of MS or MD against RNFL thickness demonstrated a negligible degree of
      determination in normal (R(2) = 0.0378 and 0.0121, respectively) and PPG groups
      (R(2) = 0.0215 and 0.0151, respectively), whereas their relationship fit a
      curvilinear regression model (R(2) = 0.6947 and 0.723) in the POAG group.
      Receiver operating characteristic (ROC) curves describing the VF parameters and
      average RNFL thickness (AVG) were evaluated to differentiate PPG from POAG eyes.
      Repeated analysis with the best-performing test parameter, pattern standard
      deviation (PSD) (AUROC = 0.937) with a cutoff of 1.9 dB, showed that regression
      profiles in the POAG group with PSD >1.9 dB maintained a strong curvilinear
      RNFL/VF relationship, whereas those with PSD <1.9 dB exhibited a relationship
      almost indistinguishable from the PPG group. CONCLUSIONS: Evaluation of the
      structure-function relationship in normal subjects and those with PPG or POAG
      showed strong curvilinear regression in POAG eyes with PSD >1.9 dB and RNFL AVG
      thickness below 70 microm, whereas no correlation was detectable above these
      values.

PMID- 17197542
TI  - Trypsin inhibitory capacity in vernal keratoconjunctivitis.
AB  - PURPOSE: To study tear trypsin inhibitory capacity (T-TIC), serum trypsin
      inhibitory capacity (S-TIC) and their relationship to matrix metalloproteinases
      (MMP)-1 and -9 in patients with vernal keratoconjunctivitis (VKC). METHODS: In
      the first phase of the study, inactivation of alpha-1 antitrypsin (AAT) by MMP-1
      and -9 was investigated in vitro. Subsequently, tear samples were collected after
      clinical evaluation from 14 patients with active VKC and 15 normal control
      subjects. Tear cytology was performed on all samples. Levels of T-TIC and S-TIC
      were determined by spectrophotometry, whereas levels of tear pro-MMP-1, pro-MMP
      9, and active MMP-1 and -9 were determined by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: MMP-1 and -9 inactivated AAT in vitro. S-TIC was significantly
      higher (P < 0.0001), and T-TIC (P < 0.0001) significantly lower in VKC samples.
      Tear levels of pro-MMP-1 and pro-MMP-9, and the activity of MMP-1 and -9 was
      significantly greater in patients with VKC than in healthy subjects (P < 0.0001).
      There was no significant correlation between T-TIC, MMP-1, and MMP-9 activity. In
      addition, T-TIC was not correlated to the total clinical score or to single
      clinical sign scores. CONCLUSIONS: In this study, tear trypsin inhibitory
      capacity was shown to be reduced and tear MMP-1 and -9 activity increased in
      patients with VKC. Although T-TIC did not correlate with VKC severity, a local
      reduced inhibitory capacity of ATT may facilitate or prolong conjunctival
      inflammation in VKC.

PMID- 17197543
TI  - Transcriptional regulation of IL-8 by Staphylococcus aureus in human conjunctival
      cells involves activation of AP-1.
AB  - PURPOSE: To identify signal transduction pathways involved in interleukin (IL)-8
      expression by human conjunctival cells challenged with Staphylococcus aureus.
      METHODS: Conjunctival cells were cultured in the presence of live or heat-killed
      S. aureus. IL-8 protein and mRNA were determined by ELISA and RT-PCR,
      respectively. Activation of mitogen-activated protein kinases (MAPKs) and NF
      kappaB was analyzed by Western blot analysis with phosphospecific antibodies.
      Conjunctival cells were transfected with wild-type (wt) or mutated IL-8 promoters
      (IL-8-97, lacking the AP-1 site; IL-8-97 mutant C/EBP; IL-8-97 mutant NF-kappaB;
      IL-8/AP-1 double mutant for C/EBP and NF-kappaB) or c-Jun-NH(2)-terminal kinase
      (JNK)-responsive GAL-c-Jun. In further experiments, cells were cotransfected with
      wt IL-8 promoter and expression plasmids for p38MAPK-responsive C/EBP homologous
      protein (CHOP) or wt or dominant negative transactivation domain mutant (TAM-67)
      c-Jun. A protein-DNA binding study was performed by electrophoretic mobility
      shift assay (EMSA), to identify the transcription factors bound to the IL-8
      promoter. RESULTS: S. aureus induced significant IL-8 expression and synthesis in
      human conjunctival epithelial cells by activating c-Jun phosphorylation and
      transactivation potential via JNK. The IL-8 promoter activation was NF-kappaB-
      and p38MAPK-independent. Transfection and EMSA experiments suggested that only AP
      1 transcription factors were necessary for optimal IL-8 expression. CONCLUSIONS:
      Human conjunctival epithelial cells possess the ability to respond to Gram
      positive S. aureus and to activate the innate immune response by the IL-8 gene
      expression. These results are the first to delineate the transcription factors
      involved in S. aureus-induced IL-8 release by conjunctival epithelium.

PMID- 17197544
TI  - Granulocyte macrophage colony-stimulating factor expression in human herpetic
      stromal keratitis: implications for the role of neutrophils in HSK.
AB  - PURPOSE: Granulocyte macrophage colony-stimulating factor (GM-CSF) is thought to
      play a key role in chronic inflammatory diseases by governing the survival and
      function of infiltrating neutrophils. The objective of this study was to
      determine the putative role of GM-CSF in the pathogenesis of human herpetic
      stromal keratitis (HSK). METHODS: Primary human corneal fibroblast (HCF) cultures
      and a telomerase-immortalized human corneal epithelial (HCE) cell line
      representative of native HCE were stimulated with the known HSK-inducing
      cytokines interferon (IFN)-gamma, interleukin (IL)-1beta, and tumor necrosis
      factor (TNF)-alpha. Alternatively, the T-cell cytokine IL-17 was added solely or
      simultaneously. Human neutrophils were incubated with conditioned medium (CM) of
      the HCF and HCE stimulated with the aforementioned cytokines, or recombinant GM
      CSF, and their viability or activation status was determined by flow cytometry.
      GM-CSF and IL-8 secretion levels in the CM were determined by ELISA. The antibody
      dependent cellular cytotoxicity (ADCC) of neutrophils toward herpes simplex virus
      (HSV)-infected HCFs was determined by flow cytometry. The expression of GM-CSF
      was determined in HSK and control corneal buttons by real-time RT-PCR and
      immunohistology. RESULTS: Compared with IFN-gamma, CM of either cell type
      stimulated with IL-1beta, or in the case of HCE cells, stimulated with TNF-alpha
      or IL-17, delayed neutrophil apoptosis significantly. Only in HCFs did IL-17
      exhibit a synergistic effect with TNF-alpha. The antiapoptotic activity was
      attributable in part to the GM-CSF secreted by the activated HCFs and HCE cells.
      GM-CSF stimulation of neutrophils induced their activation and the secretion of
      IL-8. GM-CSF did not increase significantly the ADCC reaction of neutrophils
      toward HSV-infected HCFs. Finally, GM-CSF was expressed in corneas of the
      patients with HSK but not in control subjects. CONCLUSIONS: The data suggest that
      GM-CSF, expressed by cornea-resident cells such as HCFs and HCE cells, may play a
      role in the immunopathogenesis of HSK by prolonging the survival and modulating
      the effector function of corneal infiltrating neutrophils.

PMID- 17197545
TI  - Lack of iNOS facilitates MCMV spread in the retina.
AB  - PURPOSE: The purposes of this study were to identify iNOS-producing retinal cells
      and to determine whether lack of iNOS facilitates MCMV spread and replication in
      the retina. METHODS: Immunosuppressed (IS) iNOS(-/-) mice or C57BL/6 (wild-type)
      mice were inoculated with 5 x 10(4) PFU of MCMV K181 strain (K181) via the
      supraciliary route. Injected eyes were collected at several times after
      inoculation and examined by plaque assay for replicating virus, RT-PCR for iNOS
      RNA, Western blot for iNOS protein and by staining for MCMV early antigen (EA),
      iNOS, and retinal cell antigens. RESULTS: iNOS mRNA and iNOS proteins were
      expressed in the MCMV-injected eye of wild-type mice. Most iNOS-producing cells
      were F4/80-positive, including macrophages, RPE-derived macrophages, and resident
      microglia. Significantly higher titers of virus were recovered from the injected
      eyes, and more infected cells were detected in the retina of IS iNOS(-/-) mice
      than in IS wild-type mice. Retinal necrosis and loss of retinal architecture
      throughout the retina were noted in IS iNOS(-/-) mice, whereas cytomegalic cells
      and retinitis were present only in the peripheral retina of IS wild-type mice.
      CONCLUSIONS: iNOS produced by macrophages, especially resident macrophages
      including microglia and RPE derived macrophages, plays an important role in
      limiting spread of MCMV in the retina.

PMID- 17197546
TI  - Proteolytic mechanisms underlying mitochondrial degradation in the ocular lens.
AB  - PURPOSE: To remove light-scattering structures from the visual axis, all
      intracellular organelles are eliminated from cells in the center of the
      developing ocular lens. Organelle degradation is accompanied by an increase in
      VEIDase (caspase-6-like) activity, but data from caspase-null mice suggest that
      the lens VEIDase is not caspase-6. The goal of the present work was to identify
      the lens VEIDase and determine whether it plays a role in organelle breakdown.
      METHODS: The approximate molecular mass of the lens VEIDase was determined by
      size-exclusion chromatography. Three proteasome inhibitors (NLVS, MG132, and
      clasto-lactacystin beta-lactone) were tested for their ability to inhibit lens
      VEIDase activity. Lens lysates were immunodepleted of proteasomes using an
      antibody against the 20S proteasome. To inhibit the ubiquitin-proteasome pathway
      (UPP) in vivo, lactacystin was injected into the vitreous humor of the developing
      chicken eye. The effect of lactacystin on mitochondrial degradation was assessed
      by examining the disappearance of succinate-ubiquinone oxidoreductase, an
      integral protein of the inner mitochondrial membrane. RESULTS: The lens VEIDase
      eluted at approximately 700 kDa from a size-exclusion column and was inhibited by
      the proteasome inhibitors NLVS, MG132, and clasto-lactacystin beta-lactone. In
      vivo, the trypsin-like activity of the proteasome was reduced by 60% to 70% after
      lactacystin injection. Proteasome inhibition was associated with the accumulation
      of ubiquitinated proteins and reversible opacification of the lens cortex. In
      lactacystin-injected eyes, the programmed degradation of succinate-ubiquinone
      oxidoreductase was inhibited in the central lens fiber cells. CONCLUSIONS: These
      data suggest that lens VEIDase activity is attributable to the proteasome and
      that the UPP may function in the removal of organelle components during lens
      fiber cell differentiation.

PMID- 17197547
TI  - Predicted light scattering from particles observed in human age-related nuclear
      cataracts using mie scattering theory.
AB  - PURPOSE: To employ Mie scattering theory to predict the light-scattering from
      micrometer-sized particles surrounded by lipid shells, called multilamellar
      bodies (MLBs), reported in human age-related nuclear cataracts. METHODS: Mie
      scattering theory is applicable to randomly distributed spherical and globular
      particles separated by distances much greater than the wavelength of incident
      light. With an assumed refractive index of 1.40 for nuclear cytoplasm, particle
      refractive indices from 1.33 to 1.58 were used to calculate scattering
      efficiencies for particle radii 0.05 to 3 microm and incident light with
      wavelengths (in vacuo) of 400, 550, and 700 nm. RESULTS: Surface plots of
      scattering efficiency versus particle radius and refractive index were calculated
      for coated spherical particles. Pronounced peaks and valleys identified
      combinations of particle parameters that produce high and low scattering
      efficiencies. Small particles (<0.3 microm radius) had low scattering efficiency
      over a wide range of particle refractive indices. Particles with radii 0.6 to 3
      microm and refractive indices 0.08 to 0.10 greater (or less) than the surrounding
      cytoplasm had very high scattering efficiencies. This size range corresponds well
      to MLBs in cataractous nuclei (average MLB radius, 1.4 microm) and, at an
      estimated 4000 particles/mm(3) of tissue, up to 18% of the incident light was
      scattered primarily within a 20 degrees forward cone. CONCLUSIONS: The calculated
      size of spherical particles that scatter efficiently was close to the observed
      dimensions of MLBs in cataractous nuclei. Particle refractive indices only 0.02
      units different from the surrounding cytoplasm scatter a significant amount of
      light. These results suggest that the MLBs observed in human age-related nuclear
      cataracts may be major sources of forward light scattering that reduces contrast
      of fine details, particularly under dim light.

PMID- 17197548
TI  - Effects of pharmacologically manipulated amplitude and starting point on edinger
      westphal-stimulated accommodative dynamics in rhesus monkeys.
AB  - PURPOSE: The aim of this study was to determine whether pharmacologically
      manipulated resting refraction, amplitude, and starting point affect
      accommodative and disaccommodative dynamics in anesthetized adolescent rhesus
      monkeys. METHODS: Pilocarpine and atropine were applied topically to manipulate
      resting refraction, accommodative amplitude, starting point, and end point in two
      monkeys with permanent electrodes in the Edinger-Westphal nucleus. Accommodation
      was centrally stimulated with submaximal and maximal current amplitudes. Dynamic
      accommodative responses were measured with infrared photorefraction before and
      during the course of action of the drugs. Accommodative and disaccommodative
      dynamics were analyzed in terms of peak velocity as a function of amplitude,
      starting point, and end point. RESULTS: Pilocarpine caused a myopic shift in
      resting refraction of 11.62 +/- 1.17 D. Centrally stimulated accommodative
      amplitude was 10.08 +/- 1.15 D before pilocarpine and 0.68 +/- 0.29 D after
      pilocarpine. Changes were found in accommodative dynamics as a function of
      starting point and in disaccommodative dynamics as a function of amplitude and
      end point. Accommodative amplitude was 11.25 +/- 0.18 D before atropine
      administration and 0.52 +/- 0.11 D after atropine administration. Accommodative
      dynamics as a function of amplitude were not substantially altered during the
      course of pilocarpine-induced accommodation or atropine-induced cycloplegia.
      CONCLUSIONS: Accommodative response amplitude is reduced with pilocarpine by
      shifting the eye to a more myopic state and with atropine by cycloplegia.
      Pharmacologic manipulations showed that accommodative and disaccommodative
      dynamics in anesthetized monkeys depend on amplitude, starting point, and end
      point of the response and on the contributions of neural and receptor activity.

PMID- 17197549
TI  - Fluid transport across the isolated porcine ciliary epithelium.
AB  - PURPOSE: To quantify spontaneous fluid transport across the isolated porcine
      ciliary epithelium and determine its sensitivity to the electrolyte transport
      inhibitors ouabain and bumetanide, as well as bath Cl(-) and HCO(3)(-) levels.
      METHODS: A complete annulus of ciliary body was mounted in a custom-designed
      chamber appropriate for quantifying net fluid movement, as well as the
      transepithelial potential difference (PD) across the in vitro ciliary epithelium.
      RESULTS: A spontaneous and stable fluid flow (FF) in the blood-to-aqueous
      direction was measured over a 4-hour period. This flux solely reflected the
      secretory activity of the isolated ciliary epithelium (CE), given the absence of
      externally applied osmotic or pressure gradients. In contrast to FF, the PD
      declined during the 4 hours in vitro, suggesting that the integrity of the tight
      junctions may have been compromised during this time so that an increased
      movement of counter ions via the paracellular pathway could have shunted the PD,
      while at the same time transcellular fluid transport remained unaffected. The FF
      in the blood-to-aqueous direction (2.3 +/- 0.2 muL/hr; n = 7) was eliminated by a
      unilateral reduction in the bath Cl(-) levels on the blood side of the
      preparation and restored on reintroducing the anion to the bathing medium. This
      linkage between FF and blood side [Cl(-)] is consistent with the existence of a
      net Cl(-) flux across the porcine CE in the same direction as the fluid
      transport. Addition of bumetanide to the blood-side bath inhibited FF by
      approximately 40%, whereas the removal of CO(2)/HCO(3)(-) from the blood-side
      bathing solution elicited a approximately 50% reduction in FF. Ouabain inhibited
      the FF from either side of the preparation, although the effects were more rapid
      when the glycoside was applied to the blood side of the tissue. Overall, these
      findings indicate the dependence of FF on active ionic transport by the isolated
      CE. CONCLUSIONS: Isolated porcine ciliary epithelial preparations transport fluid
      in the blood-to-aqueous direction, indicating that measurements of volumetric
      fluid flow across this preparation may serve as a suitable model for future
      studies directed toward the pharmacological control of secretion.

PMID- 17197550
TI  - Increased blood pressure induces a diameter response of retinal arterioles that
      increases with decreasing arteriolar diameter.
AB  - PURPOSE: To study the diameter response of retinal arterioles as a function of
      the arteriolar diameter. METHODS: Ten healthy young volunteers aged 22 to 33
      years were subjected to diameter measurement of four successive segments of a
      retinal arteriole with a retinal vessel analyzer (RVA). At each of the segments,
      the diameter response during an increase in the systemic blood pressure (mean
      arterial pressure [MAP]) induced by isometric exercise was compared to the
      diameter of the arterioles during rest. RESULTS: The isometric exercise induced a
      significant contraction of the studied vessel segments averaging 2.5% +/- 0.4% (P
      < 0.0001, n = 40). There was a significant negative correlation between the
      baseline diameter of the studied vessel segments and the diameter response
      induced by isometric exercise (P = 0.02). CONCLUSIONS: The blood pressure-induced
      diameter response of retinal arterioles increased with decreasing diameter of the
      vessels. The results indicate that the distal retinal arterioles play a major
      role in the regulation of retinal blood flow.

PMID- 17197551
TI  - RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in
      disease expression.
AB  - PURPOSE: Human blindness caused by mutation of visual cycle genes has been
      discussed as potentially treatable by retinoid replacement either through gene
      transfer or pharmacological bypass. Mutations in the RDH12 gene disrupt the
      visual cycle in vitro, but little is known of the in vivo effects of mutant
      RDH12, other than the association with severe early-onset autosomal recessive
      retinal disease. The relationship of retinal organization and visual function in
      patients with RDH12 mutations was determined and comparisons made with the
      disease from mutations in another visual cycle gene, RPE65. METHODS: Young
      patients with RDH12 mutations were studied with optical coherence tomography
      (OCT) and colocalized measures of vision with dark-adapted absolute thresholds.
      Results were compared to those in patients with RPE65 mutations. RESULTS: Retinal
      architecture of patients with RDH12 mutations was appreciably distorted,
      precluding identification of the normal laminae. Some RDH12-mutant retinas were
      remarkably thick and others were thin, but all had the same dysplastic pattern. A
      comparison with the structural and functional consequences in patients with
      mutations in RPE65 indicated that the pathogenesis of retinal degeneration in
      RDH12 mutations was distinctly different. CONCLUSIONS: The results demand
      critical consideration of the human disease mechanism and the therapeutic
      approach in patients with mutations in the putative visual cycle gene RDH12.

PMID- 17197553
TI  - Quantitative fluorescein angiographic analysis of choroidal neovascular
      membranes: validation and correlation with visual function.
AB  - PURPOSE: To compare computerized analysis with traditional grading methods in the
      analysis of fluorescein angiograms from patients with choroidal
      neovascularization (CNV) due to age-related macular degeneration (AMD) and to
      examine the clinical relevance of parameters generated by computerized analysis
      by testing their relationships with clinical measures of vision. METHODS: Custom
      quantitative fluorescein analysis (QFA) software was used to analyze 62
      angiograms from patients with CNV for whom distance visual acuity (DVA) data were
      available. On applying QFA, we obtained three mathematical parameters for each
      lesion component: pixel area (PA), integrated intensity (II), and positive
      fluorescence (PF). Quotients (Q) were derived for the latter two parameters by
      correcting against background (b) or optic nerve (o) fluorescence (IIQ(b), IIQ
      degrees , PFQ(b), and PFQ degrees ). The new metrics were compared with
      traditional grading parameters of classic CNV and lesion area. The relationships
      of both sets of angiographic data with measures of vision were explored by
      regression analyses. RESULTS: Weighted kappa between QFA and traditional grading
      for lesion subtype assessment was high (kappa = 0.7). Regression analyses with
      PA, IIQ(b), IIQ degrees , PFQ(b), and PFQ degrees for each lesion descriptor
      (leakage, classic CNV, occult CNV, total lesion) as independent variables and DVA
      as the dependent variable showed that in every case PFQ(b) exhibited the most
      significant relationship with vision (adjusted r(2) = 0.26). Parameter estimates
      showed that for a change of 30 units on the PFQ(b) for classic CNV, a loss of 20
      letters of DVA may be expected. No parameters from traditional grading methods
      showed statistically significant relationships with DVA. CONCLUSIONS: The markers
      of dynamic change in area and intensity of fluorescence exhibited stronger
      relationships with visual function than did area measurements alone.

PMID- 17197552
TI  - Acrolein, a toxicant in cigarette smoke, causes oxidative damage and
      mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid.
AB  - PURPOSE: To understand better the cell and molecular basis for the epidemiologic
      association between cigarette smoke, oxidant injury, and age-associated macular
      degeneration, the authors examined the effects of acrolein, a major toxicant in
      cigarette smoke, on oxidative mitochondrial damage in retinal pigment epithelial
      (RPE) cells and the reduction of this damage by lipoic acid. METHODS: Cultured
      human ARPE19 cells and primary cultures of human fetal (hf)RPE were treated with
      acrolein. The toxicity of acrolein and the protective effects of R-alpha-lipoic
      acid were examined with a variety of previously described techniques. RESULTS:
      Acute acrolein exposure exceeding 50 microM (24 hours) in ARPR19 cells caused
      toxicity, including decreases in cell viability, mitochondrial potential, GSH,
      antioxidant capacity, Nrf2 expression, enzyme activity (mitochondrial complexes
      I, II, III; superoxide dismutase; and glutathione peroxidase). Acute exposure
      also increased oxidant levels, protein carbonyls, and calcium. Continuous
      acrolein exposure over 8 or 32 days caused similar toxicity but from 10- to 100
      fold lower doses (0.1-5 microM). Pretreatment with R-alpha-lipoic acid
      effectively protected ARPE-19 cells from acrolein toxicity. Primary hfRPE cells
      were comparable to the ARPE-19 cells in sensitivity to acrolein toxicity and
      lipoic acid protection. CONCLUSIONS: These results show that acrolein is a
      mitochondrial toxicant in RPE cells and that acrolein-induced oxidative
      mitochondrial dysfunction is reduced by lipoic acid. The similar sensitivity of
      the ARPE-19 and hfRPE cells suggests that both models are useful for studying RPE
      toxicity and protection. These experiments indicate that mitochondria-targeted
      antioxidants such as lipoic acid may be an effective strategy for reducing or
      preventing chronic oxidant-induced RPE degeneration in vivo from a variety of
      sources, including cigarette smoke.

PMID- 17197554
TI  - Subretinal posterior pole injury induces selective proliferation of RPE cells in
      the periphery in in vivo studies in pigs.
AB  - PURPOSE: To study topographical differences in porcine retinal pigment epithelial
      (RPE) cell proliferation (1) in vivo, after experimental central surgical
      subretinal injury, and (2) in vitro. METHODS: Domestic pigs underwent either
      experimental RPE debridement (n = 5), subretinal amniotic membrane
      transplantation (n= 4), or both (n= 1) in the left eye. RPE cell proliferation
      was assayed by injection of the thymidine analogue 5-bromodeoxyuridine (5-BrdU)
      at postoperative day 0 and 1. RPE cells in S-phase were identified by their
      incorporation of 5-BrdU, as detected by immunohistochemistry. The in vitro
      proliferation of primary RPE isolates from the peripheral and central retina was
      assayed by a colorimetric assay and by [(3)H]thymidine incorporation. RESULTS:
      After subretinal surgery, in vivo incorporation of 5-BrdU was seen in peripheral
      RPE cells in 8 of 10 surgically treated eyes, but never in central RPE cells.
      This observation was true of both types of experimental surgery performed. In
      vitro, RPE isolates from the pre-equatorial region consistently yielded higher
      cell densities than did RPE cell isolates from more central parts of the
      epithelium. This was apparent through the three first passages of porcine RPE
      cells in culture. After 1 and 4 days in culture, pre-equatorial RPE cells had
      incorporated significantly more [(3)H]thymidine than had the more central RPE
      cells. CONCLUSIONS: Experimental subretinal surgical injury of the RPE below the
      central retina is followed within 48 hours by a peripheral, but not a central,
      proliferation of RPE cells. In vitro, peripheral RPE cells have a higher
      proliferative capacity than do central RPE cells.

PMID- 17197555
TI  - Retinal ischemia and reperfusion causes capillary degeneration: similarities to
      diabetes.
AB  - PURPOSE: Retinal neurons and vasculature interact with each other under normal
      conditions, and occlusion of the retinal vasculature can result in damage to
      retinal neurons. Whether damage to the neural retina will damage the vasculature,
      however, is less clear. This study was conducted to explore the relationship
      between vascular and nonvascular cells of the retina. The response of the retinal
      vasculature to an injury (ischemia and reperfusion; I/R) that is known to cause
      neuronal degeneration was studied. METHODS: I/R injury to the retinas was induced
      in Lewis rats and C57BL/6J mice by elevating intraocular pressure (IOP), and
      reperfusion was established immediately afterward. Some rats were pretreated with
      aminoguanidine (AMG, 50 mg/Kg BW in drinking water) before the procedure.
      Poly(ADP-ribose) polymerase (PARP) activity and expression of inducible nitric
      oxide synthase (iNOS), and cycloxygenase-2 (COX-2) were measured by Western blot
      analysis, and levels of TNF-alpha and intercellular adhesion molecule (ICAM)-1
      mRNA were measured by qPCR at 2 and 7 days after the procedure. Also at 2 and 7
      days after the I/R injury, apoptosis of retinal neural cells (demonstrated by
      TUNEL assay), density of cells in the ganglion cell layer, and thickness of
      retinas were quantitated, and the number of TUNEL-positive capillary cells and
      degenerated capillaries were assessed. Retinal neurodegeneration and capillary
      degeneration were also examined in C57BL/6J mice 2, 5, 8, and 14 days after I/R
      injury. RESULTS: As expected, loss of cells in the retinal ganglion cell layer
      was apparent 2 days after I/R injury in the rat and mouse models. In contrast,
      the retinal vasculature had essentially no pathology at this time in either
      model. Surprisingly, the number of degenerated capillaries increased greatly by 7
      to 8 days after the injury. Administration of aminoguanidine significantly
      inhibited the I/R-induced capillary degeneration as well as neurodegeneration in
      the rat model. Retinal I/R caused increased PARP activity (detected by poly(ADP
      ribosy)lated proteins), as well as upregulation of iNOS, COX-2, TNF-alpha, and
      ICAM-1 levels in rats, consistent with an inflammatory process. CONCLUSIONS:
      Capillary degeneration is an unrecognized component of acutely elevated IOP and
      develops only after neurodegeneration is severe. Thus, this finding raises the
      possibility that damage to the neural retina contributes to capillary
      degeneration. Aminoguanidine, a nonspecific inhibitor of iNOS, inhibited I/R
      induced degeneration of both neuronal and vascular cells of the retina. The model
      of retinal ischemia and reperfusion will be a useful tool for investigating the
      relationship between neuronal damage and vascular damage in glaucoma and other
      diseases such as diabetic retinopathy.

PMID- 17197556
TI  - Retinal circulatory changes associated with interferon-induced retinopathy in
      patients with hepatitis C.
AB  - PURPOSE: To evaluate the effect of interferon (IFN) therapy on retinal
      microcirculation. METHODS: Thirty-six patients with chronic hepatitis C who were
      treated with high-dose IFN were included in this prospective study. The changes
      in vessel diameter and blood velocity were measured, and the retinal blood flow
      (RBF) and wall shear rate (WSR) were calculated in the retinal arteries before
      and 2, 4, 8, 16, and 24 weeks after IFN therapy by using laser Doppler
      velocimetry. RESULTS: Retinal blood velocity, RBF, and WSR significantly (P <
      0.0001) increased in all patients, as early as 2 weeks after IFN therapy. The
      increase in RBF was independently correlated with a decrease in the red blood
      cell count. In 22 (61%) of the 36 patients asymptomatic retinopathy developed
      during treatment. In patients with retinopathy, the blood velocity and WSR
      increased, but the vessel diameter did not change, whereas the vessel diameter
      increased but the blood velocity and WSR did not change in patients without
      retinopathy 2 weeks after IFN therapy. Multiple logistic regression analysis
      showed that patient age and the change in WSR at week 2 were risk factors for the
      development of IFN-induced retinopathy. CONCLUSIONS: RBF increases in association
      with IFN therapy in patients with chronic hepatitis C. In addition, the increased
      WSR in patients with retinopathy indicates that retinal vascular endothelial
      dysfunction may be associated with IFN-induced retinopathy, because wall shear
      stress should be constant under physiologic conditions.

PMID- 17197557
TI  - Regional variations in the relationship between macular thickness measurements
      and myopia.
AB  - PURPOSE: To investigate the relationship between myopia and macular thickness, as
      measured by optical coherence tomography. METHODS: A total of 143 normal subjects
      comprising 80 eyes with high myopia (spherical equivalent [SE] < -6.0 D), 37 eyes
      with low to moderate myopia (SE between -6.0 and -0.5 D), and 26 nonmyopic eyes
      (SE > -0.5 D) were analyzed in this cross-sectional study. Total average, foveal,
      and inner and outer average macular thicknesses measured by the StratusOCT (Carl
      Zeiss Meditec Inc., Dublin, CA) were compared among the three diagnostic groups.
      Associations between macular thickness and refractive error/axial length were
      evaluated by linear regression analysis. RESULTS: The minimum foveal and average
      foveal (1-mm ring on the OCT retinal thickness map) thicknesses were
      significantly greater, and the outer ring macular (3-6-mm) thicknesses
      significantly lower in the high myopic eyes than in the low to moderate myopic
      and nonmyopic eyes. No significant difference was found in the inner ring (1-3
      mm) macular thickness measurements among the groups. There was a positive
      correlation between the axial length and the average foveal thickness (r = 0.374,
      P < 0.001). Negative correlations were found between axial length and the average
      outer ring macular thickness (r= -0.471, P < 0.001) and total average macular
      thickness (r= -0.311, P < 0.001). CONCLUSIONS: Retinal thickness is related to
      refractive error/axial length in normal subjects with regional variations in
      correlation within the 6-mm macular region. Analysis of macular thickness in the
      evaluation of macular diseases and glaucoma should be interpreted only in the
      context of refractive errors and the location of measurement.

PMID- 17197558
TI  - Multifocal ERG reveals several patterns of cone degeneration in retinitis
      pigmentosa with concentric narrowing of the visual field.
AB  - PURPOSE: To analyze multifocal ERGs (mfERGs) in patients with retinitis
      pigmentosa (RP), with constricted visual fields and visual acuity satisfactory
      for steady fixation. METHODS: The mfERGs of 86 eyes of 43 patients with various
      forms of inheritance and durations of RP were analyzed. A retinal scanning system
      with a 20-in. monitor was used to map central cone function. Electrical signals
      of the retina were detected by using DTL fiber electrodes. RESULTS: The site of
      the best response density of the mfERGs in the patients with RP was found in a
      central or eccentric position of the trace array. Depending on the position of
      the best response density in the two eyes, the patients were categorized into
      three groups. In the first group, the best response density was recorded from the
      central hexagon in both eyes, producing a central peak surrounded by very low
      responses in the three-dimensional presentation. In the second group of patients,
      the best responses were found to correspond to the central hexagon on only one
      side. In the fellow eye, however, the best response density appeared to be in an
      eccentric position. The patients in the third group did not present a central
      peak in the mfERG on either side. In scattered parts of the trace arrays, several
      acceptable responses were observed in all three groups that might represent
      patches of functioning retinal cone receptors. CONCLUSIONS: The results suggest
      highly variable central responses and groups of cones with preserved function in
      areas previously considered nonresponsive. The high variability of the central
      responses could be a result of variable foveal cone density, with differences in
      inheritance- and duration-related cone degeneration at the time of the
      examination. The authors stress the value of step-by-step analysis of the trace
      array of the mfERGs, which can reveal the still-functioning groups of cones.

PMID- 17197559
TI  - Long-term retinal toxicity of intravitreal commercially available preserved
      triamcinolone acetonide (Kenalog) in rabbit eyes.
AB  - PURPOSE: To investigate whether intravitreal Kenalog (IVTK; Bristol Meyers Squibb
      Company, Princeton, NJ) produces histologic or electroretinographic changes in
      the rabbit retina up to 3 months after injection. METHODS: Ten Dutch-belted
      rabbits were injected with 4 mg/0.1 mL Kenalog in one eye and 0.1 mL physiologic
      salt solution (PSS) in the fellow eye. Simultaneous bilateral dark-adapted
      electroretinography was performed 2 weeks and 12 weeks after injection in 10 and
      6 rabbits, respectively. Saturated a-wave amplitude, maximal scotopic b-wave
      amplitude, and individual a-wave and b-wave amplitudes of IVTK-injected and
      control eyes were compared at 2 and 12 weeks after injection. Light microscopy
      was performed on both eyes of three animals 3 months after injection.
      Immunohistochemistry was performed with antibodies recognizing vimentin and human
      alveolar macrophage (HAM)-56, markers of glial cells and macrophages,
      respectively. RESULTS: No significant difference was observed in the saturated a
      wave or maximal scotopic b-wave amplitudes between the PSS-injected eyes and the
      IVTK-injected eyes at 2 weeks (P = 0.95 and P = 0.56, respectively) and 12 weeks
      (P = 0.82 and P = 0.17) after injection. Light microscopy and
      immunohistochemistry disclosed only rare macrophages in the vitreous of IVTK
      injected eyes. Retinal layers, retinal pigment epithelium, and choriocapillaris
      in treatment and control eyes were unremarkable. CONCLUSIONS: No demonstrable
      electroretinographic or histologic changes occurred to suggest immediate or
      delayed widespread retinal toxicity of IVTK.

PMID- 17197561
TI  - A strong genetic determinant of hyperoxia-related retinal degeneration on mouse
      chromosome 6.
AB  - PURPOSE: Hyperoxia-related retinal degeneration (HRRD) is a model system in the
      mouse in which elevated oxygen levels are used to induce retinal degeneration.
      The hypothesis for the present study was that strain differences in HRRD
      susceptibility are due to allelic variants of one or more genes in the mouse
      genome whose human orthologues should be important targets for research and drug
      development. METHODS: C57BL/6J, A/J, or B.A-Chr6 mice were exposed to 75% oxygen
      (hyperoxia) or room air for 14 days. After death, one eye was fixed and processed
      for outer nuclear layer (ONL) thickness measurements. The retina and RPE/choroid
      were separately dissected from the fellow eye and processed for microarray
      analysis. Single nucleotide polymorphism (SNP) analysis for transcribed sequences
      from the C57BL/6J and A/J genomes was conducted using the NIH genome site.
      RESULTS: C57BL/6J mice developed a significant retinal degeneration in the
      inferior hemisphere after 14 days of hyperoxia. Under identical conditions, A/J
      mice exhibited only minor changes. A significant genetic effect was located on
      chromosome 6. SNP analysis of known transcribed sequences on chromosome 6
      combined with microarray expression analysis yielded 33 candidate genes.
      CONCLUSIONS: A significant genetic effect of susceptibility to HRRD is located on
      chromosome 6. In silico analysis of transcribed sequences results in a fairly
      small number of candidate genes.

PMID- 17197560
TI  - Acceleration of age-related changes in the retina in alpha-tocopherol transfer
      protein null mice fed a Vitamin E-deficient diet.
AB  - PURPOSE: To assess the role of vitamin E (VE) in age-related changes in the
      retinal tissues by using a mouse model of severe VE deficiency. METHODS: Pups of
      alpha-tocopherol transfer protein null (a-TTP(-)(/)(-)) mice were fed a VE
      deficient diet for 4 or 18 months (VE (-) group). Wild-type C57BL/6 mice were fed
      a 0.002% alpha-tocopherol-supplemented diet (VE (+) group). In various ocular
      tissues, the VE levels were measured by high-performance liquid chromatography;
      the fatty acid composition by gas chromatography (GC); and the
      hydroxyoctadecadienoic acid and 8-iso-prostaglandin F(2)(alpha) levels, which are
      biomarkers for lipid peroxidation, by GC-mass spectrometry. The retinal structure
      was assessed by light, electron, and fluorescence microscopy. RESULTS: The alpha
      tocopherol level in the retinas obtained from 4-month-old VE (-) animals was 71
      fold lower than that in the retinas obtained from the VE (+) group. In addition,
      gamma-tocopherol was not detected; thus, the VE (-) group demonstrated a more
      severe VE deficiency than ever reported. In this group, the concentration of n-3
      polyunsaturated fatty acids decreased (0.3- to 0.9-fold), whereas that of other
      classes of fatty acids was unchanged or increased. At 18 months of age, the
      number of the outer nuclear layer (ONL) nuclei was observed to be 17% lower in
      the VE (-) than in the VE (+) group (P < 0.05). Electron microscopy revealed
      larger amounts of matrix between the ONL nuclei indicating the Muller cell
      hypertrophy, greatly expanded rod outer segment discs, and a larger number of
      inclusion bodies in the retinal pigment epithelium (RPE; P < 0.05) in the VE (-)
      group. Fluorescence microscopy revealed that the autofluorescence signal was
      increased in the RPE layer in this group. When the observations of the 18-month
      old animals were compared to those of the 4-month-old animals, the
      hydroxyoctadecadienoic acid and 8-iso-prostaglandin F(2)(alpha) levels were found
      to be increased in the retina and RPE obtained from both the VE (-) and VE (+)
      groups; however, the age-related increases were more remarkable in the VE (-)
      group (2.6- to 43.5-fold) than in the VE (+) group (0.8- to 8.7-fold).
      CONCLUSIONS: The combined use of a-TTP(-)(/)(-) mice and a VE-deficient diet
      leads to a severe deficiency of VE, enhances lipid peroxidation in the retina,
      and accelerates degenerative damage of the retina with age.

PMID- 17197562
TI  - Minocycline protects photoreceptors from light and oxidative stress in primary
      bovine retinal cell culture.
AB  - PURPOSE: To determine whether minocycline, a compound known to protect the retina
      against light-induced damage in rodent models, and its structurally related
      analogues would protect photoreceptor cells in primary bovine retinal cell
      culture against light and oxidative stress. METHODS: Minocycline and its
      analogues were tested in primary retinal cell culture to see whether they would
      inhibit light or oxidative stress-induced cell death. Primary cell cultures
      composed of photoreceptors, bipolar cells, and glial cells were prepared from
      bovine retinas. The extent of cell death induced by light or oxidative stress was
      assessed by using Sytox Green (Invitrogen-Molecular Probes, Eugene, OR) a nucleic
      acid dye uptake assay. Differential protection of photoreceptor cells from stress
      were examined using immunocytochemistry. RESULTS: Minocycline and methacycline
      were cytoprotective against light- or oxidative stress-induced damage of bovine
      primary photoreceptors in culture with an EC(50) < 10 microM. In contrast,
      structurally related analogues such as demeclocycline, meclocycline, and
      doxycycline were phototoxic at >3 to >10 microM. Though demeclocycline was found
      to be phototoxic, it was cytoprotective (EC(50) = 5 microM) against oxidative
      stress in the absence of exposure to light. CONCLUSIONS: The protective action of
      minocycline against light-induced damage in the cell-based assays agrees with
      earlier reports in animal models and suggests that the in vitro assay using
      bovine primary retinal cell culture is a suitable model for evaluating compounds
      for retinal protection. Cellular protection or toxicity produced by structurally
      related compounds show that minor structural modifications can alter the function
      of minocycline and lead to potent retinal protective compounds.

PMID- 17197563
TI  - Role of nonproteolytically activated prorenin in pathologic, but not physiologic,
      retinal neovascularization.
AB  - PURPOSE: Recently, it was revealed that the inhibition of nonproteolytic
      activation of prorenin led to significant suppression of ocular inflammation in
      endotoxin-induced uveitis. The purpose of the present study was to investigate
      whether nonproteolytically activated prorenin plays a role in ischemia-induced
      retinal neovascularization. METHODS: C57BL/6 neonatal mice were reared in an 80%
      concentration of oxygen from postnatal (P) day 7 to P12, followed by room-air
      breathing to P17 to induce ischemia-initiated retinal neovascularization. Tissue
      localization of activated prorenin and prorenin receptor was examined by
      immunohistochemistry. Animals received intraperitoneal injections of handle
      region peptide (HRP), a decoy peptide corresponding to the handle region of
      prorenin, which inhibits prorenin receptor-mediated upregulation of the renin
      angiotensin system (RAS). A concanavalin A lectin perfusion-labeling technique
      was used to evaluate the areas of physiologic and pathologic retinal new vessels
      and the number of leukocytes adhering to the vasculature. Retinal mRNA expression
      and protein levels of intercellular adhesion molecule (ICAM)-1, vascular
      endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1, and VEGFR-2 were
      examined by RT-PCR and ELISA. RESULTS: Retinal vessels in ischemic retinopathy
      eyes were positive for activated prorenin and prorenin receptor. Pathologic, but
      not physiologic, retinal neovascularization was significantly attenuated in HRP
      treated mice compared with vehicle- or control peptide-treated animals. The
      number of adherent leukocytes was also significantly reduced. Retinal mRNA
      expression and protein levels of ICAM-1, VEGF, VEGFR-1, and VEGFR-2 in ischemic
      retinopathy were also significantly suppressed by the application of HRP.
      CONCLUSIONS: The present findings suggest that nonproteolytic activation of
      prorenin selectively promotes pathologic, but not physiologic, retinal
      neovascularization through the inflammatory processes related to pathologic
      neovascularization.

PMID- 17197564
TI  - Neurotrophic factors minimize the retinal toxicity of verteporfin photodynamic
      therapy.
AB  - PURPOSE: A prior study showed that brain-derived neurotrophic factor (BDNF)
      rescues photoreceptors from collateral retinal damage caused by photodynamic
      therapy (PDT). This study was conducted to determine whether ciliary neurotrophic
      factor (CNTF), a combination of BDNF and CNTF, or pigment epithelial cell-derived
      growth factor (PEDF) might protect photoreceptors and retinal function more
      effectively than BDNF. Also investigated was whether protection would be observed
      after a second round of PDT with adjunctive BDNF treatment. METHODS: Normal rats
      received intravitreal injections of BDNF, CNTF, a combination of BDNF and CNTF,
      or PEDF in one eye and PBS in the other 2 days before PDT. Retinal function and
      photoreceptor survival were assessed with multifocal ERG (mfERG) and histology 1
      week after PDT. Another group of rats received two courses of PDT 3 months apart,
      with injection of BDNF 2 days before each treatment. RESULTS: All factors
      significantly increased photoreceptor survival. The combination of BDNF and CNTF
      rescued more photoreceptors than either factor alone. Only BDNF improved retinal
      function 1 week after PDT, with CNTF and the combination of BDNF and CNTF
      reducing mfERG responses. BDNF injection before a second round of PDT improved
      mfERG responses and retinal structure. CONCLUSIONS: BDNF is the most effective
      single factor among those tested for neuroprotection and improvement of retinal
      function after PDT, although a combination of BDNF and CNTF rescues more
      photoreceptors. Adjunctive treatment with BDNF also protects retinal structure
      and function through two rounds of PDT, suggesting its potential value for
      patients who require multiple treatments.

PMID- 17197565
TI  - Differential sensitivity of cones to iron-mediated oxidative damage.
AB  - PURPOSE: In this study, the hypothesis that increased intraocular levels of iron
      cause oxidative damage to the retina was tested. METHODS: Adult C57BL/6 mice were
      given an intravitreous injection of saline or 0.10, 0.25, or 0.50 mM FeSO(4).
      Scotopic electroretinograms (ERGs) were performed 3, 7, and 14 days after
      injection, and photopic ERGs were performed on day 14. Hydroethidine was used to
      identify superoxide radicals and lipid peroxidation was visualized by staining
      for hydroxynonenal (HNE). Retinal cell death was evaluated by TUNEL and
      measurement of inner nuclear layer (INL) and outer nuclear layer (ONL) thickness.
      Levels of rhodopsin and cone-opsin mRNA were measured by quantitative real time
      RT-PCR. Cone density was assessed by peanut agglutinin staining and confocal
      microscopy. RESULTS: Compared with retinas in saline-injected eyes, retinas from
      eyes injected with FeSO(4) showed greater fluorescence after intravenous
      injection of hydroethidine due to superoxide radicals in photoreceptors, greater
      photoreceptor staining for HNE, a marker of lipid peroxidation, and increased
      expression of Heme oxygenase 1, an indicator of oxidative stress. ERG b-wave
      amplitudes were reduced (photopic > scotopic) in FeSO(4)-injected eyes compared
      with those in saline-injected eyes. Numerous TUNEL-stained nuclei were seen along
      the outer border of the ONL, the location of cone cell nuclei, at 1 and 2 days
      after injection of FeSO(4). In FeSO(4)-injected eyes, the thickness of the ONL,
      but not the INL, was significantly reduced, and 17 days after injection, there
      were 3.8- and 2.6-fold reductions in the mRNAs for M-cone and S-cone opsin,
      respectively, whereas there was no significant difference in rhodopsin mRNA.
      Confocal microscopy of peanut agglutinin-stained sections showed dose-dependent
      FeSO(4)-induced cone drop out. CONCLUSIONS: Increased intraocular levels of
      FeSO(4) cause oxidative damage to photoreceptors with greater damage to cones
      than rods. This finding suggests that the oxidative defense system of cones
      differs from that of rods and other retinal cells, and that cones are more
      susceptible to damage from the type of oxidative stress imposed by iron.

PMID- 17197567
TI  - Cytotoxic effect of spermine on retinal pigment epithelial cells.
AB  - PURPOSE: A prior study showed inactivation of ornithine-delta-aminotransferase
      (OAT)-deficient human retinal pigment epithelial (RPE) cells by a specific
      irreversible inhibitor (5-fluoromethylornithine; 5-FMO) leading to cell death, in
      an in vitro model of gyrate atrophy (GA) of the choroid and retina. In the
      present study, the cytotoxicity of metabolites of ornithine, especially spermine,
      in RPE cells was investigated, to clarify the mechanism of ornithine cytotoxicity
      in RPE cells. METHODS: RPE cells were incubated with ornithine or compounds
      involved in ornithine metabolic pathways. The effects on RPE cell viability and
      proliferative activity were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) colorimetric and [(3)H]thymidine incorporation
      assays. Incorporation of spermine into RPE cells was examined by using
      [(14)C]spermine and dansyl-spermine. To assess spermine-induced RPE cell death,
      cells were double stained with annexin V and propidium iodide and subjected to
      flow cytometry. RESULTS: Ornithine, arginine, glutamate, proline, creatine,
      glycine, and putrescine exhibited no effects on the viability and proliferative
      activities of RPE cells, whereas spermidine and spermine (10 mM) inhibited
      [(3)H]thymidine incorporation by 13% and 89%, respectively. The inhibition of
      [(3)H]thymidine incorporation by spermine was dose dependent and was observed as
      early as 4 hours after addition. Further, spermine was incorporated and
      accumulated in the perinuclear region of RPE cells. Apoptotic RPE cell death was
      induced by spermine in a dose-dependent manner. CONCLUSIONS: The present results
      demonstrated that excessive spermine is cytotoxic to RPE cells and suggest that
      metabolites of ornithine, especially spermine, may be involved in the mechanism
      of RPE degeneration in GA.

PMID- 17197568
TI  - Ornithine transport via cationic amino acid transporter-1 is involved in
      ornithine cytotoxicity in retinal pigment epithelial cells.
AB  - PURPOSE: A prior report showed ornithine cytotoxicity in ornithine-delta
      aminotransferase (OAT)-deficient human retinal pigment epithelial (RPE) cells in
      an in vitro model of gyrate atrophy of the choroid and retina. This study was
      intended to clarify the mechanism of ornithine cytotoxicity and to determine the
      responsible amino acid transporters. METHODS: The mRNA expression of amino acid
      transporters in human telomerase reverse transcriptase (hTERT)-RPE cells was
      examined by reverse transcription polymerase chain reaction (RT-PCR) and Northern
      blot analysis. Carrier-mediated ornithine transport via the L-type amino acid
      transporter (LAT)1, LAT2, cationic amino acid transporter (CAT)-1, and y(+)LAT2
      systems was evaluated by short interfering (si)RNA-mediated gene silencing. The
      cytoprotective effect of CAT-1-specific siRNA on ornithine cytotoxicity was
      measured using quantitative analysis of cellular adenosine triphosphate (ATP) at
      24 hours after treatment with ornithine in OAT-deficient RPE cells. RESULTS:
      LAT1, LAT2, CAT-1, and y(+)LAT2 mRNA expression was detected by Northern blot
      analysis, whereas RT-PCR revealed that LAT1, LAT2, y(+)LAT1, y(+)LAT2, CAT-1, and
      b(0,+)AT mRNAs were expressed together with the heterodimeric glycoproteins 4F2hc
      and rBAT in hTERT-RPE cells. l-[(14)C]ornithine uptake in hTERT-RPE cells was
      decreased by 46.6% and 22.0% by CAT-1 and y(+)LAT2 siRNA, respectively, whereas
      LAT1 and LAT2 siRNA had no significant effect. Further, CAT-1 silencing by siRNA
      reduced ornithine cytotoxicity in OAT-deficient RPE cells. CONCLUSIONS: The
      results suggest that ornithine transport via CAT-1 may play a crucial role in
      ornithine cytotoxicity in hTERT-RPE cells. Reduction of the ornithine transport
      via CAT-1 may be a new target for treatment of gyrate atrophy.

PMID- 17197566
TI  - Retinal stem cells transplanted into models of late stages of retinitis
      pigmentosa preferentially adopt a glial or a retinal ganglion cell fate.
AB  - PURPOSE: To characterize the potential of newborn retinal stem cells (RSCs)
      isolated from the radial glia population to integrate the retina, this study was
      conducted to investigate the fate of in vitro expanded RSCs transplanted into
      retinas devoid of photoreceptors (adult rd1 and old VPP mice and rhodopsin
      mutated transgenic mice) or partially degenerated retina (adult VPP mice)
      retinas. METHODS: Populations of RSCs and progenitor cells were isolated either
      from DBA2J newborn mice and labeled with the red lipophilic fluorescent dye
      (PKH26) or from GFP (green fluorescent protein) transgenic mice. After expansion
      in EGF+FGF2 (epidermal growth factor+fibroblast growth factor), cells were
      transplanted intravitreally or subretinally into the eyes of adult wild-type,
      transgenic mice undergoing slow (VPP strain) or rapid (rd1 strain) retinal
      degeneration. RESULTS: Only limited migration and differentiation of the cells
      were observed in normal mice injected subretinally or in VPP and rd1 mice
      injected intravitreally. After subretinal injection in old VPP mice, transplanted
      cells massively migrated into the ganglion cell layer and, at 1 and 4 weeks after
      injection, harbored neuronal and glial markers expressed locally, such as beta
      tubulin-III, NeuN, Brn3b, or glial fibrillary acidic protein (GFAP), with a
      marked preference for the glial phenotype. In adult VPP retinas, the grafted
      cells behaved similarly. Few grafted cells stayed in the degenerating outer
      nuclear layer (ONL). These cells were, in rare cases, positive for rhodopsin or
      recoverin, markers specific for photoreceptors and some bipolar cells.
      CONCLUSIONS: These results show that the grafted cells preferentially integrate
      into the GCL and IPL and express ganglion cell or glial markers, thus exhibiting
      migratory and differentiation preferences when injected subretinally. It also
      appears that the retina, whether partially degenerated or already degenerated,
      does not provide signals to induce massive differentiation of RSCs into
      photoreceptors. This observation suggests that a predifferentiation of RSCs into
      photoreceptors before transplantation may be necessary to obtain graft
      integration in the ONL.

PMID- 17197569
TI  - Vulnerability of dopaminergic amacrine cells and optic nerve myelination to
      prenatal endotoxin exposure.
AB  - PURPOSE: Intrauterine infection has been linked to preterm delivery and
      neurologic injury. The purpose of this study was to investigate the effects of
      fetal inflammation induced by exposure to endotoxin on the structure and
      neurochemistry of the retina and optic nerve. METHODS: The bacterial endotoxin,
      lipopolysaccharide (LPS), was administered to fetal sheep at approximately 0.65
      of the approximately 147-day gestation period via repeated bolus doses (1
      microg/kg per day) over 5 days, with fetal retinas and optic nerves assessed 10
      days after the first LPS exposure. RESULTS: In the retina, the total number of
      tyrosine hydroxylase immunoreactive (TH-IR), dopaminergic amacrine cells was
      reduced (P < 0.05) in LPS-exposed compared with control fetuses. There was no
      difference in the number of ChAT-, substance P-, or NADPH-d-positive amacrine
      cells. The total number of myelinated axons in the optic nerve was not different
      (P > 0.05) between groups; however, the myelin sheath was thinner (P < 0.05) in
      LPS-exposed fetuses. CONCLUSIONS: Prenatal exposure to repeated doses of
      endotoxin results in alterations to the retina and optic nerve with specific
      effects on dopaminergic neurons and myelination, respectively. These findings
      could have implications for visual function.

PMID- 17197571
TI  - MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic
      fibrosis bronchial cells.
AB  - Chronic lung inflammation in cystic fibrosis (CF) is specifically characterized
      by predominant endobronchial neutrophil infiltrates, colonization by Pseudomonas
      aeruginosa, and elevated levels of cytokines and chemokines, first of all IL-8.
      The extensive inflammatory process in CF lungs is the basis of progressive tissue
      damage and is largely considered detrimental, making antiinflammatory approaches
      a relevant therapeutic target. This neutrophil-dominated inflammation seems to be
      related to an excessive proinflammatory signaling, originating from the same
      surface epithelial cells expressing the defective CF transmembrane conductance
      regulator (CFTR) protein, although the underlying mechanisms have not been
      completely elucidated. To investigate the relationship between defective CFTR and
      the inflammatory response to P. aeruginosa in CF airway cells, we studied the
      effect of the DeltaF508 CFTR corrector, benzo(c)quinolizinium (MPB)-07 (Dormer et
      al., J Cell Science 2001;114:4073-4081). CF bronchial epithelial IB3-1 and CuFi-1
      cells overproduced the inflammatory molecules, IL-8 and intercellular adhesion
      molecule (ICAM)-1, in response to P. aeruginosa, compared with the wild-type,
      CFTR-expressing bronchial cells, S9, and NuLi-1 cells. In both IB3-1 and CuFi-1
      cells, the corrector MPB-07 dramatically reduces the IL-8 and ICAM-1 mRNA
      expression elicited by P. aeruginosa infection. Correction of CFTR-dependent Cl-
      efflux was confirmed in MPB-07-treated IB3-1 and CuFi-1 cells. In conclusion, the
      DeltaF508 CFTR corrector MPB-07 produces an antiinflammatory effect in CF
      bronchial cells exposed to P. aeruginosa in vitro.

PMID- 17197572
TI  - Building models.

PMID- 17197570
TI  - ALK-5 mediates endogenous and TGF-beta1-induced expression of connective tissue
      growth factor in embryonic lung.
AB  - Transforming growth factor-beta1 (TGF-beta1) has been implicated as a major
      negative regulator of lung branching morphogenesis. Since connective tissue
      growth factor (CTGF) is a downstream mediator of TGF-beta1 effects on mesenchymal
      cells, we hypothesized that TGF-beta1 induces CTGF expression in mouse embryonic
      lung explants and that CTGF mediates TGF-beta1 inhibition of branching
      morphogenesis. We show that addition of TGF-beta1 to the serum-free medium of
      embryonic day (E)12.5 lung explant cultures inhibited branching morphogenesis and
      induced CTGF mRNA expression in time- and dose-dependent manners. In contrast to
      basal endogenous CTGF protein, which was exclusively localized in the distal
      airway epithelium, TGF-beta1-induced CTGF protein was localized in both the
      epithelium and the mesenchyme. Addition of exogenous CTGF to culture medium
      directly inhibited branching morphogenesis. To identify the signal transduction
      pathway through which TGF-beta1 induces CTGF, we used SB431542, a specific
      inhibitor for TGF-beta type I receptor (TbetaRI)/ALK-5 to block TGF-beta1-induced
      Smad2/3 phosphorylation. Consequently, SB431542 stimulated normal branching
      morphogenesis and blocked TGF-beta1 inhibition of branching. Furthermore, SB
      431542 blocked both endogenous and TGF-beta1-induced expression of CTGF mRNA and
      protein. These results demonstrate for the first time that TGF-beta1 induces CTGF
      expression in mouse embryonic lung explants, that CTGF inhibits branching
      morphogenesis, and that both endogenous and TGF-beta1-induced CTGF expression are
      mediated by the TbetaRI/ALK-5-dependent Smad2 signaling pathway.

PMID- 17197575
TI  - The drop-jump screening test: difference in lower limb control by gender and
      effect of neuromuscular training in female athletes.

PMID- 17197574
TI  - Prolonged superficial local cryotherapy attenuates microcirculatory impairment,
      regional inflammation, and muscle necrosis after closed soft tissue injury in
      rats.
AB  - BACKGROUND: Closed soft tissue injury induces progressive microvascular
      dysfunction and regional inflammation. The authors tested the hypothesis that
      adverse trauma-induced effects can be reduced by local cooling. While superficial
      cooling reduces swelling, pain, and cellular oxygen demand, the effects of
      cryotherapy on posttraumatic microcirculation are incompletely understood. STUDY
      DESIGN: Controlled laboratory study. METHODS: After a standardized closed soft
      tissue injury to the left tibial compartment, male rats were randomly subjected
      to percutaneous perfusion for 6 hours with 0.9% NaCL (controls; room temperature)
      or cold NaCL (cryotherapy; 8 degrees C) (n = 7 per group). Uninjured rats served
      as shams (n = 7). Microcirculatory changes and leukocyte adherence were
      determined by intravital microscopy. Intramuscular pressure was measured, and
      invasion of granulocytes and macrophages was assessed by immunohistochemistry.
      Edema and tissue damage was quantified by gravimetry and decreased desmin
      staining. RESULTS: Closed soft tissue injury significantly decreased functional
      capillary density (240 +/- 12 cm(-1)); increased microvascular permeability (0.75
      +/- 0.03), endothelial leukocyte adherence (995 +/- 77/cm(2)), granulocyte (182.0
      +/- 25.5/mm(2)) and macrophage infiltration, edema formation, and myonecrosis
      (ratio: 2.95 +/- 0.45) within the left extensor digitorum longus muscle.
      Cryotherapy for 6 hours significantly restored diminished functional capillary
      density (393 +/- 35), markedly decreased elevated intramuscular pressure, reduced
      the number of adhering (462 +/- 188/cm(2)) and invading granulocytes (119 +/-
      28), and attenuated tissue damage (ratio: 1.7 +/- 0.17). CONCLUSION: The
      hypothesis that prolonged cooling reduces posttraumatic microvascular
      dysfunction, inflammation, and structural impairment was confirmed. CLINICAL
      RELEVANCE: These results may have therapeutic implications as cryotherapy after
      closed soft tissue injury is a valuable therapeutic approach to improve nutritive
      perfusion and attenuate leukocyte-mediated tissue destruction. The risk for
      evolving compartment syndrome may be reduced, thereby preventing further
      irreversible aggravation.

PMID- 17197576
TI  - The effects of medialization and anteromedialization of the tibial tubercle on
      patellofemoral mechanics and kinematics.

PMID- 17197577
TI  - Anterior shoulder stabilization in collision athletes: arthroscopic versus open
      Bankart repair.

PMID- 17197578
TI  - A comparison between clinical assessment and magnetic resonance imaging of acute
      hamstring injuries.

PMID- 17197579
TI  - Dynamic ultrasound as a selection tool for reducing achilles tendon reruptures.

PMID- 17197580
TI  - Adapting to the times.

PMID- 17197581
TI  - Retropubic compared with transobturator tape placement in treatment of urinary
      incontinence: a randomized controlled trial.
AB  - OBJECTIVE: To compare the intraoperative and immediate postoperative performance
      of the retropubic tension-free vaginal tape (TVT) procedure with that of the
      transobturator tension-free vaginal tape (TVT-O) procedure as primary treatment
      for female urinary stress incontinence. METHODS: Randomized multicenter
      comparative trial including four university hospitals and three central hospitals
      in Finland. Assessment preoperatively and 2 months postoperatively included a
      cough stress test and the following condition-specific quality of life
      questionnaires: the Urinary Incontinence Severity Score (UISS), the Detrusor
      Instability Score, the Incontinence Impact Questionnaire-Short Form, the
      Urogenital Distress Inventory-Short Form, and a visual analog scale (VAS).
      Operation time, theater time, hospital stay, intraoperative and immediate
      postoperative complications were recorded. RESULTS: Of the 273 originally
      randomized patients, 267 underwent the allocated operation, 136 in the TVT group
      and 131 in the TVT-O group. No significant differences in objective or subjective
      cure rates were detected. Patients in the TVT-O group had a significantly longer
      hospital stay, needed significantly more postoperative opiate analgesia and had
      significantly more complications than the patients in the TVT group. Patients in
      both groups had a significant postoperative improvement in quality of life, as
      indicated by the results of all the questionnaires used, with no difference
      between the groups. CONCLUSION: The TVT and the TVT-O procedures perform equally
      in terms of objective and subjective cure. The statistically significant higher
      complication rate in the TVT-O group is not regarded as clinically significant.
      CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov), NCT00379314 LEVEL OF
      EVIDENCE: I.

PMID- 17197582
TI  - Association of lymphadenectomy and survival in stage I ovarian cancer patients.
AB  - OBJECTIVE: To estimate the survival impact of lymphadenectomy in women diagnosed
      with clinical stage I ovarian cancer. METHODS: Demographic and clinicopathologic
      information were obtained from the Surveillance, Epidemiology and End Results
      Program between 1988 and 2001. Data were analyzed using Kaplan-Meier methods and
      Cox proportional hazards regression. RESULTS: A total of 6,686 women had clinical
      stage I ovarian cancer (median age 54 years, range 1-99). Of this total, 75.9% of
      patients were Caucasian, 8.3% were Hispanic, 5.8% were African American, and 7.3%
      were Asian. Epithelial tumors were present in 85.8% of the women, and 2,862
      (42.8%) patients underwent lymphadenectomy. Patients aged 50 years or more were
      less likely to undergo lymphadenectomy compared with their younger cohorts (39.8%
      compared with 60.2%, P<.001). Only 32.7% of African-American women had
      lymphadenectomy compared with 42.7% of Caucasian women, 47.2% of Hispanics, and
      48.8% of Asians (P<.001). Lymphadenectomy was associated with improved 5-year
      disease-specific survival of all patients from 87.0% to 92.6% (P<.001). More
      specifically, lymphadenectomy improved the survival in those with non-clear cell
      epithelial ovarian cancer (85.9% to 93.3%, P<.001) but not in those with clear
      cell carcinoma, germ cell tumors, sex cord stromal tumors, and sarcomas.
      Moreover, the extent of lymphadenectomy (0 nodes, less than 10 nodes, and 10 or
      more nodes) increased the survival rates from 87.0% to 91.9% to 93.8%,
      respectively (P<.001). On multivariable analysis, the extent of lymphadenectomy
      was a significant prognostic factor for improved survival, independently of other
      factors such as age, stage, histology, and grade of disease. CONCLUSION: Our data
      suggest that women with stage I non-clear cell ovarian cancers who underwent
      lymphadenectomy had a significant improvement in survival. LEVEL OF EVIDENCE: II.

PMID- 17197583
TI  - Laparoscopic occlusion compared with embolization of uterine vessels: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare clinical outcome 6 months after treatment with bilateral
      laparoscopic occlusion of the uterine artery versus uterine leiomyoma
      embolization. METHODS: Sixty-six premenopausal women with symptomatic uterine
      leiomyomata were randomized to treatment with either laparoscopic occlusion of
      uterine arteries or uterine leiomyoma embolization. The primary outcome was
      reduction of blood loss from pretreatment to 6 months postoperatively, measured
      by a Pictorial Bleeding Assessment Chart. Secondary outcomes included patients'
      own assessment of symptom reduction, postoperative pain assessed using visual
      analog scales, ketobemidone used postoperatively, complications, secondary
      interventions, and failures. RESULTS: Fifty-eight women were included; 6-month
      follow-up data were available for 28 participants in each group. The percentage
      reduction in Pictorial Bleeding Assessment Chart scores did not differ between
      the treatment groups (52% after uterine leiomyoma embolization and 53% after
      laparoscopy, P=.96). The study had 52% power to detect a 20% difference on the
      Pictorial Bleeding Assessment Chart. Fewer participants in the group treated with
      uterine leiomyoma embolization complained of heavy bleeding after 6 months (4%
      compared with 21%, P=.044). The postoperative use of ketobemidone was higher
      after uterine leiomyoma embolization (46 mg compared with 12 mg, P<.001).
      CONCLUSION: Both laparoscopic occlusion of uterine vessels and embolizaton of
      uterine leiomyoma improved clinical symptoms in the majority of patients.
      Participants with the laparoscopic procedure had less postoperative pain but
      heavier menstrual bleeding 6 months after treatment. A larger study and longer
      follow-up is necessary before a definite conclusion can be made regarding the
      most effective treatment. CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov),
      NCT00277680 LEVEL OF EVIDENCE: I.

PMID- 17197584
TI  - Risk factors for anal sphincter tear during vaginal delivery.
AB  - OBJECTIVE: To identify risk factors associated with anal sphincter tear during
      vaginal delivery and to identify opportunities for preventing this cause of fecal
      incontinence in young women. METHODS: We used baseline data from two groups of
      women who participated in the Childbirth and Pelvic Symptoms (CAPS) study: those
      women who delivered vaginally, either those with or those without a recognized
      anal sphincter tear. Univariable analyses of demographic and obstetric
      information identified factors associated with anal sphincter tear. We calculated
      odds ratios (ORs) for these factors alone and in combination, adjusted for
      maternal age, race, and gestational age. RESULTS: We included data from 797
      primaparous women: 407 with a recognized anal sphincter tear and 390 without.
      Based on univariable analysis, a woman with a sphincter tear was more likely to
      be older, to be white, to have longer gestation or prolonged second stage of
      labor, to have a larger infant (birth weight/head circumference), or an infant
      who was in occiput posterior position, or to have an episiotomy or operative
      delivery. Logistic regression found forceps delivery (OR 13.6, 95% confidence
      interval [CI] 7.9-23.2) and episiotomy (OR 5.3, 95% CI 3.8-7.6) were strongly
      associated with a sphincter tear. The combination of forceps and episiotomy was
      markedly associated with sphincter tear (OR 25.3, 95% CI 10.2-62.6). The addition
      of epidural anesthesia to forceps and episiotomy increased the OR to 41.0 (95% CI
      13.5-124.4). CONCLUSION: Our results highlight the existence of modifiable
      obstetric interventions that increase the risk of anal sphincter tear during
      vaginal delivery. Our results may be used by clinicians and women to help inform
      their decisions regarding obstetric interventions. LEVEL OF EVIDENCE: II.

PMID- 17197585
TI  - Pathologic examination of the placenta and observed practice.
AB  - OBJECTIVE: To estimate the percentage of deliveries eligible for pathologic
      examination of the placenta and compare with observed practice using the College
      of American Pathologists' (CAP) 1997 guidelines for examination of the placenta.
      METHODS: Records were reviewed from all live-birth deliveries 20 weeks or more of
      gestation in 2001 at Strong Memorial Hospital. The expected number of deliveries
      with CAP recommended indications was determined and compared with the observed
      number of deliveries in which the placenta was actually examined. Descriptive
      statistics, independent t tests, chi(2) tests, difference between two population
      proportions test, odds ratios, 95% confidence intervals, and multiple logistic
      regression were used to analyze the data. RESULTS: The observed number and
      percentage of deliveries with CAP recommended indications that had pathologic
      placental examination, 575 and 18.2% (95% confidence interval 16.9-19.6), was
      significantly lower (P<.001) than expected, 1,185 and 37.5% (95% confidence
      interval 35.8-39.2). The placenta was examined less frequently than expected in 9
      of 14 categories. Independent predictors of examination of the placenta were
      gross placental abnormalities, multiple gestation, prematurity, peripartum fever,
      neonatal intensive care unit care of infant, cesarean delivery, and delivery by a
      maternal-fetal medicine specialist. CONCLUSION: Using the CAP guidelines for
      submission of the placenta would result in pathologic examination in 37.5% of all
      deliveries. Less than one half of all deliveries in which the placenta was
      eligible for submission were actually examined. Current advances in our
      understanding of pathologic conditions of the placenta and their relation to
      infant outcomes may warrant re-evaluating policy on placental examination at
      institutional and national levels. LEVEL OF EVIDENCE: II.

PMID- 17197586
TI  - Long-term outcome after fetal transfusion for hydrops associated with parvovirus
      B19 infection.
AB  - OBJECTIVE: To evaluate neurodevelopmental status of children treated with
      intrauterine red blood cell and platelet transfusion for fetal hydrops caused by
      parvovirus B19. METHODS: Maternal and neonatal records of all intrauterine
      transfusions for congenital parvovirus B19 infection in our center between 1997
      and 2005 were reviewed. Congenital B19 virus infection was confirmed by the
      presence of parvovirus B19-specific immunoglobulin M or parvovirus B19 DNA in
      fetal blood samples. All children underwent a general pediatric and neurological
      examination. Primary outcome measure was neurodevelopmental status (developmental
      index by Bayley Scales of Infant Development or Snijders-Oomen test). Secondary
      outcome measure was general health status of surviving children. RESULTS: A total
      of 25 intrauterine transfusions were performed in 24 hydropic fetuses. Median
      fetal hemoglobin concentration, platelet count, and blood pH before intrauterine
      transfusions were 4.5 g/dL (range 2.4-11.4 g/dL), 79x10(9)/L (range 37
      238x10(9)/L) and 7.36 (range 7.31-7.51), respectively. Sixteen survivors aged 6
      months to 8 years were included in the follow-up study. Eleven children (68%)
      were normal, and 5 children (32%) demonstrated a delayed psychomotor development
      with an suboptimal neurological examination (mild delay n=3, severe delay n=2).
      Neurodevelopmental status did not correlate with pre-intrauterine transfusion
      hemoglobin, platelet, or blood pH values. Growth and general health status were
      normal in all. Two children had minor congenital defects. CONCLUSION:
      Neurodevelopmental status was abnormal in 5 of 16 survivors and was not related
      to the severity of fetal anemia and acidemia. We hypothesize that fetal
      parvovirus B19 infection may induce central nervous system damage. LEVEL OF
      EVIDENCE: III.

PMID- 17197587
TI  - Effects of teamwork training on adverse outcomes and process of care in labor and
      delivery: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of teamwork training on the occurrence of
      adverse outcomes and process of care in labor and delivery. METHODS: A cluster
      randomized controlled trial was conducted at seven intervention and eight control
      hospitals. The intervention was a standardized teamwork training curriculum based
      on crew resource management that emphasized communication and team structure. The
      primary outcome was the proportion of deliveries at 20 weeks or more of gestation
      in which one or more adverse maternal or neonatal outcomes or both occurred
      (Adverse Outcome Index). Additional outcomes included 11 clinical process
      measures. RESULTS: A total of 1,307 personnel were trained and 28,536 deliveries
      analyzed. At baseline, there were no differences in demographic or delivery
      characteristics between the groups. The mean Adverse Outcome Index prevalence was
      similar in the control and intervention groups, both at baseline and after
      implementation of teamwork training (9.4% versus 9.0% and 7.2% versus 8.3%,
      respectively). The intracluster correlation coefficient was 0.015, with a
      resultant wide confidence interval for the difference in mean Adverse Outcome
      Index between groups (-5.6% to 3.2%). One process measure, the time from the
      decision to perform an immediate cesarean delivery to the incision, differed
      significantly after team training (33.3 minutes versus 21.2 minutes, P=.03).
      CONCLUSION: Training, as was conducted and implemented, did not transfer to a
      detectable impact in this study. The Adverse Outcome Index could be an important
      tool for comparing obstetric outcomes within and between institutions to help
      guide quality improvement. CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov),
      NCT00381056 LEVEL OF EVIDENCE: I.

PMID- 17197588
TI  - Cesarean delivery on maternal request: obstetrician-gynecologists' knowledge,
      perception, and practice patterns.
AB  - OBJECTIVE: To examine obstetrician-gynecologists' knowledge, opinions, and
      practice patterns related to cesarean delivery on maternal request. METHODS:
      Questionnaires were mailed to 1,031 American College of Obstetricians and
      Gynecologists Fellows in February 2006, with a response rate of 68%. The
      questionnaire queried respondents' demographic characteristics, practices and
      attitudes surrounding vaginal and cesarean deliveries, knowledge and beliefs
      regarding the risks and benefits of elective and nonelective cesarean delivery,
      and counseling practices and department policies for cesarean delivery on
      maternal request. RESULTS: About half of respondents believe women have the right
      to cesarean delivery on maternal request, and a similar percentage acknowledge
      having performed at least one cesarean delivery on maternal request. Fifty-eight
      percent of respondents note an increase in patient inquiries regarding cesarean
      delivery over the past year, yet most of their practices do not have a policy
      regarding this procedure. Respondents attribute the increase in inquiries to the
      increase of information from the media and to convenience. Respondents cited more
      risks than benefits of cesarean delivery on maternal request, and nearly all
      discuss these risks with patients who are considering one. Females were more
      negative toward cesarean delivery on maternal request than males and endorsed
      more risks and fewer benefits. There were no relationships between assessment of
      risks and benefits or practice with clinician age or patient characteristics.
      CONCLUSION: Most obstetrician-gynecologists in this study recognized an increased
      demand for cesarean delivery on maternal request within their practices, while
      believing that the risks of this procedure outweigh the benefits. Clinicians
      would benefit from strong evidence regarding risks and benefits, evidence that is
      crucial to guiding policy making with regard to cesarean delivery on maternal
      request. LEVEL OF EVIDENCE: III.

PMID- 17197589
TI  - Cesarean delivery or vaginal birth: a survey of patient and clinician thresholds.
AB  - OBJECTIVE: To estimate what level of additional fetal risk women and their
      caregivers in late pregnancy considered acceptable to avoid a cesarean and
      achieve a vaginal birth. METHODS: Six hundred women in late pregnancy and 294
      obstetric consultants, registrars, midwives, and medical students were recruited
      to the study. With the assistance of a visual probability aid representing 10,000
      births, they were asked to consider what level of fetal risk of death or serious
      disability they would consider acceptable to avoid cesarean and achieve vaginal
      birth. RESULTS: The median level of fetal risk deemed acceptable to achieve a
      vaginal birth for pregnant women was 10 per 10,000 births (95% confidence
      interval [CI] 10-13 per 10,000), although the range of responses was wide (1
      5,000 per 10,000). Among staff, the median level of acceptable fetal risk was 13
      per 10,000 births (95% CI 10-20 per 10,000). Women participating in lower
      intervention models of care, such as the birth center or team midwifery, were
      more tolerant of fetal risk (odds ratios [ORs] 2.1, 95% CI 1.6-2.9 and 1.5, 95%
      CI 1.0-2.3, for accepting a fetal risk of 20 per 10,000 or greater), whereas
      women with a complicated pregnancy were less tolerant of fetal risk (OR 0.7, 95%
      CI 0.5-0.9). CONCLUSION: Pregnant women and their caregivers have a low tolerance
      for fetal risk associated with vaginal birth. This study demonstrates the
      difficulty of minimizing obstetric intervention rates in the face of high
      expectations for fetal outcome. Obstetric and demographic factors were found to
      significantly impact the "acceptable fetal risk" threshold, which highlights the
      importance of individualized counseling regarding mode of birth. LEVEL OF
      EVIDENCE: III.

PMID- 17197590
TI  - Simple antenatal preparation to improve breastfeeding practice: a randomized
      controlled trial.
AB  - OBJECTIVE: To address the impact of simple antenatal educational interventions on
      breastfeeding practice. METHODS: A randomized controlled trial was carried out in
      a tertiary referral center from May 2002 to December 2004. A random sample of
      eligible low-risk antenatal patients was recruited from clinics in the National
      University Hospital, Singapore. Group A received breastfeeding educational
      material and individual coaching from a lactation counselor. Group B received
      breastfeeding educational material with no counseling. Group C received routine
      antenatal care only. RESULTS: A total of 401 women were recruited. Mothers
      receiving individual counseling and educational material practiced exclusive and
      predominant breastfeeding more often than mothers receiving routine care alone at
      3 months (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.2-5.4) and 6 months
      (OR 2.4, 95% CI 1.0-5.7) postpartum. More mothers practiced exclusive and
      predominant breastfeeding at 6 months among women receiving individual counseling
      compared with women exposed to educational material alone (OR 2.5, 95% CI 1.0
      6.3). CONCLUSION: Where breastfeeding practices are suboptimal, simple one
      encounter antenatal education and counseling significantly improve breastfeeding
      practice up to 3 months after delivery. Provision of printed or audiovisual
      educational material is not enough. Health care workers should make every effort
      to have one face-to-face encounter to discuss breastfeeding with expectant
      mothers before they deliver. CLINICAL TRIAL REGISTRATION:
      (www.ClinicalTrials.gov), NCT002770192 LEVEL OF EVIDENCE: I.

PMID- 17197591
TI  - Physical activity and fetal growth during pregnancy.
AB  - OBJECTIVE: To assess the separate and combined relationships of aerobic physical
      activity during pregnancy, maternal weight gain during pregnancy, and height to
      the fetal growth ratio. METHODS: The aerobic physical activity of 51 healthy,
      nonsmoking pregnant women was assessed for 48 hours at both 20 and 32 weeks of
      pregnancy by accelerometry, heart rate monitoring, and physical activity recall.
      We analyzed the relationship between maternal physical activity and the fetal
      growth ratio. RESULTS: All women included in the analysis completed healthy,
      uncomplicated pregnancies and delivered infants with a weight range of 2,743
      4,943 g. Aerobic physical activity assessed by accelerometry was strongly and
      inversely associated with fetal growth ratio (r=-0.42; P<.002). Infants born to
      women in the highest quartile of physical activity weighed 608 g less than
      infants born to women in the lowest quartile. The inverse relationship between
      physical activity and fetal growth ratio was moderated by maternal height;
      virtually all the effect was seen in mothers taller than the sample median (1.65
      m). Similar relationships were found across methods of physical activity
      measurement. CONCLUSION: Aerobic physical activity in pregnancy may be an
      important determinant of birth weight within the normal range, especially in
      taller mothers. LEVEL OF EVIDENCE: II.

PMID- 17197592
TI  - Intracervical block and pain perception during the performance of a
      hysterosalpingogram: a randomized controlled trial.
AB  - OBJECTIVE: To estimate whether an intracervical block of 1% lidocaine decreased
      pain perception compared with placebo during the performance of a
      hysterosalpingogram. METHODS: A randomized controlled trial was conducted with
      120 patients assessing pain perception during a hysterosalpingogram. Patients
      were randomly assigned to one of three groups. Patients received either a 1%
      lidocaine intracervical block, an intracervical saline injection, or no
      injection. Visual analog (VAS) and qualitative scales were used to assess study
      participants' pain at six different time points during the hysterosalpingogram.
      RESULTS: Subjects receiving the lidocaine block had significantly less pain
      (P<.001) by VAS during tenaculum placement (approximately 61% less, 1.303 cm) and
      with tenaculum traction (approximately 40% less, 2.804 cm) compared with both the
      intracervical saline injection group and the no injection group (tenaculum
      placement, 3.384 cm and 3.354 cm, and tenaculum traction, 4.705cm and 4.961 cm,
      respectively). There was no improvement seen with pain perception during
      instillation of the contrast in the lidocaine group compared with the saline or
      no injection group (P<.073). Subjects who received the saline injection had
      statistically more pain (P<.001) by VAS (2.647 cm) immediately after the
      injection compared with the lidocaine (approximately 79% greater, 1.476 cm) and
      no injection groups (115% greater, 1.232 cm). CONCLUSION: Lidocaine intracervical
      block provides better pain relief than placebo during tenaculum placement and
      tenaculum traction during a hysterosalpingogram. This study suggests that
      patients should be offered an intracervical block before placement of the
      cervical tenaculum to decrease pain during the performance of a
      hysterosalpingogram. CLINICAL TRIAL REGISTRATION: (www.ClinicalTrials.gov),
      NCT00372658 LEVEL OF EVIDENCE: I.

PMID- 17197593
TI  - Race, insurance status, and tubal sterilization.
AB  - OBJECTIVE: To examine the independent effects of race or ethnicity and insurance
      status on use of tubal sterilization rates. METHODS: This study used cross
      sectional data collected by the 2002 National Survey of Family Growth. The survey
      is designed to represent women and men aged 15-44 years in the household
      population of the United States. Our main outcome measure was tubal sterilization
      at any time before interview. A multivariable logistic regression model was used
      to estimate the effects of race or ethnicity and insurance status on rates of
      tubal sterilization after adjusting for important confounders. RESULTS: The
      sample consisted of 7,643 women: 66% were white, 15% were Hispanic, and 14% were
      African American; 68% had private insurance and 32% had public or no insurance.
      After adjusting for age, insurance status, parity, income, education, marital
      status, and religion, African-American women were more likely than white women to
      undergo tubal sterilization (adjusted odds ratio 1.43, 95% confidence interval
      1.08-1.88). After adjusting for age, race or ethnicity, parity, income,
      education, marital status, and religion, women with public or no insurance were
      more likely to undergo sterilization compared with women with private insurance
      (adjusted odds ratio 1.38, 95% confidence interval 1.09-1.74). CONCLUSION:
      African-American women and women with no or public insurance were more likely to
      have undergone tubal sterilization compared with white women and women with
      private insurance, respectively. Additional research to identify factors that
      influence women's decision to undergo sterilization is warranted. LEVEL OF
      EVIDENCE: II.

PMID- 17197594
TI  - Human uterus retrieval from a multi-organ donor.
AB  - OBJECTIVE: To determine if a uterus can be retrieved for reproductive organ
      transplantation and to describe the surgical technique. METHODS: We participated
      in a local organ donor network retrieval team for over 6 months. Heart-beating,
      brain-dead multi-organ donors were identified through an existing donor network
      following routine protocols. RESULTS: After institutional review board and organ
      donor network approval of the uterus transplantation project, approximately 1,800
      eligible organ donors were identified as required by legislation. Multi-organ
      procurement surgery took place in approximate 150 of these, with nine
      specifically consented for the uterus retrieval. Regularly performed multi-organ
      transplantation retrievals included the uterus without complications in eight
      donors. Pedicles used included the ovarian, uterine, or internal iliac vessels.
      After retrieval, serial histology sections throughout the period of cold
      ischemia, taken every 15-30 minutes, showed no signs of change over 12 hours of
      cold ischemia. CONCLUSION: The human uterus can be obtained from local organ
      donor networks using existing protocols. LEVEL OF EVIDENCE: III.

PMID- 17197595
TI  - Sexual behaviors after universal screening of sexually transmitted infections in
      healthy young women.
AB  - OBJECTIVE: To prospectively study the relationship between diagnosis of sexually
      transmitted infections (STIs) at entry to U.S. Marines recruit training and
      subsequent sexual behaviors during vacation. METHODS: Of all women entering
      recruit training (June 1999-June 2000), 2,157 (94%) voluntarily enrolled. At
      baseline, women received universal screening for Chlamydia trachomatis, Neisseria
      gonorrhoeae, and Trichomonas vaginalis and treatment and counseling for positive
      STIs. Recruit training (13 weeks) precluded any social activities. Unrestricted
      vacation followed (median 10 days). After training resumed (3 weeks),
      questionnaires and repeat STI screening were administered. Multivariable logistic
      regression examined STI diagnosis at baseline as a predictor for risky sexual
      behaviors at vacation and STI-positive diagnosis after vacation. RESULTS: The
      study was completed by 1,712 (79%) women (median age 18 years); 1,038 reported
      sexual activity during vacation; 71% used condoms inconsistently; 19% had casual
      partners. At baseline, 152 (15%) tested STI-positive. Baseline STI diagnosis was
      unrelated to inconsistent condom use, nonmonogamous partnerships, or multiple
      partnerships. However, women testing STI-positive at baseline were more likely to
      test STI-positive after vacation (adjusted odds ratio 3.74, 95% confidence
      interval 2.10-6.65). Baseline STI diagnosis predicted casual partnerships among
      women aged 19-21 years (adjusted odds ratio 2.48, 95% confidence interval 1.12
      5.50). CONCLUSION: Substantial numbers of women engaged in risky sexual behaviors
      after universal STI screening and counseling. Compared with STI-negative women,
      STI-positive women were at increased risk for subsequent STI acquisition
      regardless of their similar behaviors. As universal STI screening is increasingly
      implemented, follow-up care will likely be required to further reduce risky
      behaviors and address network-level factors. LEVEL OF EVIDENCE: II.

PMID- 17197596
TI  - Prevalence of bacterial vaginosis: 2001-2004 National Health and Nutrition
      Examination Survey data.
AB  - OBJECTIVE: To estimate the prevalence and correlates of bacterial vaginosis among
      women between the ages of 14 and 49 years in the United States. METHODS: Data
      from the 2001-2001 and 2003-2004 National Health and Nutrition Examination
      Surveys were combined. Correlates of bacterial vaginosis evaluated included
      sociodemographic characteristics (age, race or ethnicity, education, poverty
      income ratio) and sexual history (age of first intercourse, number of sexual
      partners). Crude and adjusted odds ratios and 95% confidence intervals were
      estimated from logistic regression analyses. RESULTS: Almost one third of women
      (29%) were positive for bacterial vaginosis. Bacterial vaginosis prevalence
      varied with age, race or ethnicity, education, and poverty. Black, non-Hispanic
      (odds ratio [OR] 3.13, 95% confidence interval [CI] 2.58-3.80) and Mexican
      American (OR 1.29, 95% CI 0.99-1.69) women had higher odds of bacterial vaginosis
      than white, non-Hispanic women after adjustment for other sociodemographic
      characteristics. Douching in the past 6 months was also an important predictor of
      bacterial vaginosis prevalence (OR 1.93, 95% CI 1.54-2.40). CONCLUSION: Bacterial
      vaginosis is a common condition among U.S. women, and the prevalence is similar
      to that in many treatment-seeking populations. Further studies are needed to
      disentangle the interactions between race or ethnicity and other sociodemographic
      characteristics. LEVEL OF EVIDENCE: III.

PMID- 17197597
TI  - Maternal serum cytokines in preterm premature rupture of membranes.
AB  - OBJECTIVE: To estimate whether maternal serum interleukin (IL)-6 or granulocyte
      colony-stimulating factor (G-CSF) obtained daily are elevated in women with
      preterm premature rupture of membranes who develop funisitis. METHODS: Daily
      blood samples were obtained from women with preterm premature rupture of
      membranes and analyzed for IL-6 and G-CSF by enzyme-linked immunosorbent assay.
      Funisitis was determined by placental examination. Observations were stratified
      based on the presence or absence of funisitis and analyzed. Proportional hazards
      models were used to evaluate time-to-delivery on the basis of diagnostic IL-6 and
      G-CSF levels, determined by receiver operating characteristic curve analysis.
      RESULTS: Of the 107 patients available for analysis, 54 (50%) had evidence of
      funisitis after delivery. Patients with funisitis were more likely to deliver at
      an earlier gestational age (28.5 weeks compared with 31.5 weeks, P<.001) and have
      Medicaid insurance (57% compared with 39%, P=.04). Serum IL-6 and G-CSF were
      elevated 24 to 48 hours before delivery in women with preterm premature rupture
      of membranes with funisitis compared with those without funisitis (IL-6, 7.5
      compared with 2.8 pg/mL, P<.001; G-CSF, 121.7 compared with 56.9 pg/mL, P=.002).
      Using values identified by the receiver operating characteristic curve, elevated
      serum IL-6 in the interval 24-72 hours before delivery was significantly
      associated with funisitis (P<.03), even after controlling for gestational age and
      insurance status. CONCLUSION: Maternal serum IL-6 and G-CSF appear to be
      biomarkers in the identification of women with preterm premature rupture of
      membranes likely to develop funisitis. LEVEL OF EVIDENCE: II.

PMID- 17197598
TI  - Adaptations of the rat vagina in pregnancy to accommodate delivery.
AB  - OBJECTIVE: To characterize ultrastructural changes in the rat vagina in
      pregnancy, delivery, and postpartum, focusing on collagen architecture and smooth
      muscle cell morphology. METHODS: The vagina of four virgin, four midpregnant,
      four late pregnant, four immediate, and four late post-vaginal-delivery rats were
      examined by transmission electron microscopy. Images were classified into one of
      four categories based on collagen fibril area fraction, with group 1 containing
      the highest number of collagen fibers per unit area and group 4 containing the
      lowest. Smooth muscle cells were characterized into three cell types
      ("synthetic," "intermediate," and "contractile") based on the volume fraction of
      cytoplasm occupied by organelles compared with myofibrils. RESULTS: Quantitative
      analysis demonstrated that 76% of collagen fibers in virgin rats were categorized
      as group 1 or 2 compared with 49% in midpregnant, 40% in late pregnant, and 23%
      in immediate postpartum animals (P=0.006). Late postpartum tissue seemed similar
      to virgin tissue (77%). Midpregnant (37%), late-pregnant (34%) and immediate
      postpartum animals (43%) contained a higher proportion of synthetic smooth muscle
      cells compared with virgins (20%) and late postpartum animals (21%) (P=.02).
      Contractile smooth muscle cells predominated in virgin (64%) and late postpartum
      animals (70%) compared with midpregnant (42%), late pregnant (50%) and immediate
      postpartum (50%, P=.05). CONCLUSION: In pregnancy, collagen fiber area decreased
      while smooth muscle cells transformed from a contractile to a synthetic
      phenotype. The late postpartum period returned to prepregnant levels for both
      collagen and smooth muscle cell morphologies. It is likely that these changes
      represent adaptations to minimize trauma to the vagina during passage of the
      fetus.

PMID- 17197599
TI  - Biomechanical adaptations of the rat vagina and supportive tissues in pregnancy
      to accommodate delivery.
AB  - OBJECTIVE: We hypothesize that in pregnancy and at the time of delivery, the
      vagina and supportive tissues undergo dramatic alterations to accommodate passage
      of the fetus. In this study, we sought to characterize these changes in the rat
      using an established biomechanical testing protocol. METHODS: Seventy-four 3
      month-old Long Evans rats divided into virgin, mid and late pregnant, vaginal
      delivery (immediate and 4-week postpartum), and abdominal delivery (immediate and
      4-week postpartum) groups were killed. The biomechanical properties of the vagina
      and supportive tissues were tested intact as a complex under loading conditions
      that simulate downward distension. Data were analyzed using analysis of variance
      and post hoc comparisons. RESULTS: Mean linear stiffness (ability of the specimen
      to resist distension) and ultimate load at failure (maximal resistance of the
      specimen to distension before disruption) were decreased in pregnancy and at
      delivery, regardless of delivery route (Ps<.001). Maximal distension was
      increased at time of delivery (Ps<.001). Four weeks after vaginal delivery, all
      biomechanical characteristics returned to at least virgin values. CONCLUSION: In
      the rat, the biomechanical characteristics affording distensibility of the vagina
      and supportive tissues increased in pregnancy and even further at delivery. It is
      likely that these represent maternal tissue adaptations that facilitate delivery
      of the fetus(es).

PMID- 17197600
TI  - Maternal uterine artery Doppler flow velocimetry and the risk of stillbirth.
AB  - OBJECTIVE: We sought to relate the risk of antepartum stillbirth to uterine
      artery Doppler flow velocimetry at 22-24 weeks. METHODS: Data were available from
      30,519 unselected women from seven units in the UK who had uterine artery Doppler
      performed between 22 and 24 weeks of gestation. The risk of stillbirth (n=109)
      was assessed using time to event and logistic regression analysis. Stillbirths
      were subdivided into placental (due to abruption, preeclampsia, or growth
      restriction) or unexplained. RESULTS: The risk of placental stillbirth was
      increased among women with a mean pulsatility index in the top decile (adjusted
      hazard ratio [HR] 5.5, 95% confidence interval [CI] 2.8-10.6) and those with a
      bilateral notch (adjusted HR 3.9, 95% CI 2.0-7.8). The relationship between a
      mean pulsatility index in the top decile and the risk of unexplained stillbirth
      was weaker (adjusted HR 2.5, 95% CI 1.1-5.6) and there was no association with a
      bilateral notch. Placental stillbirths occurred at earlier gestations than
      unexplained stillbirths (median [interquartile range] 30 [26-36] compared with 38
      [36-40], P<.001). Consequently, being in the top 5% of predicted risk of
      stillbirth on the basis of the combination of mean pulsatility index and notching
      was a good predictor (sensitivity, specificity, and positive likelihood ratio) of
      all cause stillbirth up to 32 weeks (58%, 95%, and 12.1, respectively) but a poor
      predictor of stillbirth at later gestations (7%, 95%, and 1.3, respectively).
      CONCLUSION: Abnormal uterine artery Doppler was a better predictor of the risk of
      stillbirth due to placental causes than unexplained stillbirth. Consequently,
      abnormal uterine artery Doppler was a good predictor of stillbirth at extreme
      preterm gestations but a poor predictor of stillbirth at term. LEVEL OF EVIDENCE:
      II.

PMID- 17197601
TI  - Fetal death.
AB  - The death of a formed fetus is one of the most emotionally devastating events for
      parents and clinicians. With improved care for conditions such as RhD
      alloimmunization, diabetes, and preeclampsia, the rate of fetal death in the
      United States decreased substantially in the mid twentieth century. However, the
      past several decades have seen much greater reductions in neonatal death rates
      than in fetal death rates. As such, fetal death remains a significant and
      understudied problem that now accounts for almost 50% of all perinatal deaths.
      The availability of prostaglandins has greatly facilitated delivery options for
      patients with fetal death. Risk factors for fetal death include African American
      race, advanced maternal age, obesity, smoking, prior fetal death, maternal
      diseases, and fetal growth impairment. There are numerous causes of fetal death,
      including genetic conditions, infections, placental abnormalities, and fetal
      maternal hemorrhage. Many cases of fetal death do not undergo adequate evaluation
      for possible causes. Perinatal autopsy and placental examination are perhaps the
      most valuable tests for the evaluation of fetal death. Antenatal surveillance and
      emotional support are the mainstays of subsequent pregnancy management. Outcomes
      may be improved in women with diabetes, hypertension, red cell alloimmunization,
      and antiphospholipid syndrome. However, there is considerable room for further
      reduction in the fetal death rate.

PMID- 17197602
TI  - Mapping the theories of preeclampsia and the role of angiogenic factors: a
      systematic review.
AB  - OBJECTIVE: To evaluate claims that elevated soluble fms-like tyrosine kinase-1
      receptor (sFlt-1) and decreased placental growth factor predict preeclampsia.
      DATA SOURCES: MEDLINE (1966-March 2006), EMBASE (1980-June 2006), POPLINE (1980
      June 2006), CINAHL (1982-June 2006), and LILACS (1982-June 2006) were searched,
      and experts contacted. METHODS OF STUDY SELECTION: Studies identified and
      included were those reporting blood and urine levels of sFlt-1 or placental
      growth factor obtained before gestational week 30 or overt preeclampsia.
      TABULATION, INTEGRATION, AND RESULTS: Ten of 184 available studies analyzing sFlt
      1 and 14 of 319 studies analyzing placental growth factor were included in this
      review. There was considerable interreport heterogeneity in methodology and
      results for sFlt-1 measured before gestational week 25. After week 25 placental
      growth factor and sFlt-1 levels varied consistently between the normal pregnancy
      group and women destined to develop preeclampsia, achieving significance in women
      who developed severe preeclampsia. CONCLUSION: Third-trimester increases in sFlt
      1 and decreases in placental growth factor levels are associated with
      preeclampsia, specifically severe disease, based on retrospective data. The
      evidence is insufficient to recommend these markers to be used for screening, and
      prospective studies employing rigorous laboratory and study design criteria are
      needed to determine the clinical usefulness of these tests.

PMID- 17197603
TI  - Population effect of increased access to emergency contraceptive pills: a
      systematic review.
AB  - OBJECTIVE: We systematically reviewed data on effects of increased access to
      emergency contraceptive pills on pregnancy rates and use of the pills. DATA
      SOURCES: We searched MEDLINE, POPLINE, EMBASE, and LILACS, and we consulted with
      experts. METHODS OF STUDY SELECTION: We included studies that compared the effect
      of different levels of access to emergency contraceptive pills on pregnancy
      rates, use of the pills, and other outcomes. TABULATION, INTEGRATION, AND
      RESULTS: Of the 717 articles identified, we selected 23 for review. The studies
      included randomized trials, cohort studies, and evaluations of community
      interventions. The quality of these studies varied. In all but one study,
      increased access to emergency contraceptive pills was associated with greater
      use. However, no study found an effect on pregnancy or abortion rates.
      CONCLUSION: Increased access to emergency contraceptive pills enhances use but
      has not been shown to reduce unintended pregnancy rates. Further research is
      needed to explain this finding and to define the best ways to use emergency
      contraception to produce a public health benefit.

PMID- 17197608
TI  - Selective magnesium sulfate prophylaxis for the prevention of eclampsia in women
      with gestational hypertension.

PMID- 17197609
TI  - Selective magnesium sulfate prophylaxis for the prevention of eclampsia in women
      with gestational hypertension.

PMID- 17197610
TI  - Risk of urinary incontinence after childbirth: a 10-year prospective cohort
      study.

PMID- 17197611
TI  - Placenta previa, placenta accreta, and vasa previa.

PMID- 17197612
TI  - Accuracy of ultrasonography and magnetic resonance imaging in the diagnosis of
      placenta accreta.

PMID- 17197613
TI  - Chorionic villus sampling compared with amniocentesis and the difference in the
      rate of pregnancy loss.

PMID- 17197614
TI  - Chorionic villus sampling compared with amniocentesis and the difference in the
      rate of pregnancy loss.

PMID- 17197615
TI  - ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities.
AB  - In the last decade, numerous markers and strategies for Down syndrome screening
      have been developed. Algorithms that combine ultrasound and serum markers in the
      first and second trimesters have been evaluated. Furthermore, the practice of
      using age cutoffs to determine whether women should be offered screening or
      invasive diagnostic testing has been challenged. The purpose of this document is
      to 1) present and evaluate the best available evidence for the use of
      ultrasonographic and serum markers for selected aneuploidy screening in pregnancy
      and 2) offer practical recommendations for implementing Down syndrome screening
      in practice.

PMID- 17197616
TI  - ACOG Practice Bulletin No. 78: hemoglobinopathies in pregnancy.
AB  - The hemoglobinopathies are a heterogeneous group of single-gene disorders that
      includes the structural hemoglobin variants and the thalassemias. More than 270
      million people worldwide are heterozygous carriers of hereditary disorders of
      hemoglobin, and at least 300,000 affected homozygotes or compound heterozygotes
      are born each year. The purpose of this document is to review the most common
      hemoglobinopathies and to provide recommendations for screening and clinical
      management of hemoglobinopathies during pregnancy.

PMID- 17197617
TI  - ACOG Committee Opinion No. 359: commercial enterprises in medical practice.
AB  - Increasing numbers of physicians sell and promote both medical and nonmedical
      products as part of their practices. Physicians always have rendered advice and
      treatment for a fee, and this practice is appropriate. It is unethical under most
      circumstances, however, for physicians to sell or promote medical or nonmedical
      products or services for their financial benefit. The following activities are
      considered unethical: sale of prescription drugs to be used at home, sale or
      promotion of nonprescription medicine, sale or promotion of presumptively
      therapeutic agents that generally are not accepted as part of standard medical
      practice, sale or promotion of non-health-related items, recruitment of patients
      or other health care professionals into multilevel marketing arrangements, and
      sale or promotion of any product in whose sale the physician has a significant
      financial interest. It is ethical and appropriate, however, to sell products to
      patients as follows: sale of devices or drugs that require professional
      administration in the office setting; sale of therapeutic agents, when no other
      facilities can provide them at reasonable convenience and at reasonable cost;
      sale of products that clearly are external to the patient-physician relationship,
      when such a sale would be considered appropriate in an external relationship; and
      sale of low-cost products for the benefit of community organizations. A rationale
      is provided for both the prohibited activities and exceptions.

PMID- 17197618
TI  - ACOG Committee Opinion No. 358: professional responsibilities in obstetric
      gynecologic education.
AB  - Physicians must learn new skills in a manner consistent with their ethical
      obligations to benefit the patient, to do no harm, and to respect a patient's
      right to make informed decisions. Patients should be given the opportunity to
      consent to or refuse treatment by students. Students must hold in confidence any
      information they learn about patients. The relationship between teacher and
      student involves an imbalance of power and the risk of exploitation of a student
      for the benefit of the teacher. Students should not be placed in situations where
      they must provide care or perform procedures for which they are not qualified and
      not adequately supervised. Students have the obligation to be honest,
      conscientious, and respectful in their relationships with their teachers. They
      should act in ways that preserve the dignity of patients and do not undermine
      relationships between patients and their physicians. If a student observes
      unethical behavior or incompetent conduct by a teacher, the appropriate
      institutional authority should be informed. Institutions have an obligation to
      provide a work environment that enhances professional competence by ensuring that
      students and residents work reasonable hours, helping them balance education and
      patient care responsibilities; providing adequate support services; and, in the
      case of residents, providing reasonable salaries and benefits. With increasing
      numbers of women in education programs, special attention must be given to the
      parallel demands of pregnancy and career goals.

PMID- 17197619
TI  - Genetic alterations in thyroid cancer: the role of mouse models.
AB  - Thyroid carcinomas are the most common endocrine neoplasms in humans, with a
      globally increasing incidence. Thyroid follicular cells and neuroendocrine
      (parafollicular) C cells are each susceptible to neoplastic transformation,
      resulting in thyroid cancers of differing phenotypes with unique associated
      genetic mutations and clinical outcomes. Over the past 15 years, several
      sophisticated genetically engineered mouse models of thyroid cancer have been
      created to further our understanding of the genetic events leading to thyroid
      carcinogenesis in vivo. The most significant mouse models of papillary,
      follicular, anaplastic, and medullary thyroid carcinoma are highlighted, with
      particular emphasis on the relationship between the relevant oncogenes in these
      models and genetic events in the naturally occurring human disease. Limitations
      of each model are presented, and the need for additional models to better
      recapitulate certain aspects of the human disease is discussed.

PMID- 17197620
TI  - Epithelioid variant of hemangioma and hemangiosarcoma in the dog, horse, and cow.
AB  - Epithelioid hemangiomas, hemangioendotheliomas, and angiosarcomas are well
      recognized histologic variants of endothelial tumors in humans that in the past
      have been confused with neoplasms of epithelial or histiocytic origin. We
      describe 12 epithelioid endothelial vascular tumors in 8 dogs, 3 horses, and 1
      cow that share microscopic features with these tumors in humans. Ten tumors were
      located within the dermis and subcutis, 1 in the gastrocnemius tendon, and 1 in
      the skeletal muscle of the thigh. Key histologic features were the plump,
      epithelioid appearance of neoplastic endothelial cells and occasional cytoplasmic
      vacuolation, which rarely contained a single erythrocyte. Patterns of epithelioid
      endothelial cell growth ranged from conventional vasoformative structures to
      glandlike acini and short ducts to solid, sheetlike arrangements. All tumors were
      positive for endothelial markers: 12/12 (100%) were positive for von Willebrand
      factor with variable intensity and distribution and 9/9 (100%) were positive for
      CD31. All 12 were negative for cytokeratin. We subdivided these tumors into
      epithelioid hemangiomas (n = 3) and hemangiosarcomas (n = 9) based on
      conventional morphologic criteria, growth pattern (invasive or not), and
      metastasis (known in 1 case at the time of biopsy). Additional follow-up
      information obtained by a written questionnaire was available for 6/12 (50%)
      animals and revealed local recurrence in 3 animals (1 epithelioid hemangioma and
      2 epithelioid hemangiosarcoma) and regional metastasis in 3 animals (all
      epithelioid hemangiosarcomas). This series represents a novel group of vascular
      tumors in domestic animals of which there are only 3 previous cases reported in
      the veterinary literature.

PMID- 17197621
TI  - Myofasciitis in the domestic ferret.
AB  - Since late 2003, an inflammatory disease of muscle and fascia has been diagnosed
      in several ferrets at Northwest ZooPath, and this report describes the condition
      in 17 ferrets. It is a disease of young ferrets, characterized by rapid onset of
      clinical signs, high fever, neutrophilic leukocytosis, treatment failure, and
      death (or euthanasia). Gross lesions include atrophy of skeletal muscle; red and
      white mottling and dilatation of the esophagus; and splenomegaly. Histologically,
      moderate to severe suppurative to pyogranulomatous inflammation is in the
      skeletal muscle and the fascia at multiple sites, including esophagus, heart,
      limbs, body wall, head, and lumbar regions. Myeloid hyperplasia of spleen and/or
      bone marrow also is a prominent feature. Ultrastructural lesions include
      mitochondrial swelling, intracellular edema, disruption of myofibrils and Z
      bands. Bacterial and viral cultures, electron microscopy, immunohistochemistry,
      and polymerase chain reaction were negative for a variety of infectious agents.
      The clinical presentation and distribution of lesions suggests that polymyositis
      in domestic ferrets is likely a distinct entity. The etiopathogenesis if this
      condition is not known.

PMID- 17197622
TI  - Prevalence and histopathologic characteristics of pancreatitis in cats.
AB  - Despite the high prevalence of feline pancreatic disease, no detailed description
      on the histopathologic nature of this disease is currently available in the
      literature. In this study we characterize the distribution and histopathologic
      changes commonly found in feline pancreases, correlate the lesions with age and
      gastrointestinal GI and extra-gastrointestinal disease, and compare the
      pancreatic lesions in cats with those in humans. The entire pancreas was removed
      and examined from 115 cats presented for necropsy irrespective of the cause of
      death. Histologic sections from left limb, right limb, and body were scored for
      lesions of acute (AP) and chronic pancreatitis (CP) with a scoring system based
      on similar systems used in human and veterinary literature. The lesions of CP in
      cats resemble CP in humans, with fibrosis being more prominent than inflammatory
      changes. Cystic degeneration gradually increased as other lesions of CP were more
      prominent. A distinct nodular change of zymogen depletion and acinar cell
      dysplasia not associated with pancreatitis was prominent in 15.6% of the
      pancreases. Histologically, AP consisted of neutrophilic inflammation associated
      with interstitial edema and necrosis of mesenteric fat. An overall prevalence of
      67%, and 45% in clinically normal animals, was identified. CP was found in 69
      (60.0%) pancreases, and 58 (50.4%) had CP only, with a significant correlation
      between age and occurrence of CP. There was a statistically significant higher
      prevalence of CP in the left limb in animals with gastrointestinal disease. AP
      was present in 18 animals (15.7%) of which 7 animals had AP only (6.1%).

PMID- 17197623
TI  - CNS hypomyelination in Rat Terrier dogs with congenital goiter and a mutation in
      the thyroid peroxidase gene.
AB  - Arrested physical development and neurologic abnormalities were identified in 3
      of 5 Rat Terrier puppies at 9 weeks of age. Bilaterally firm symmetrical masses
      were palpated in the region of the thyroid glands. Low serum total (T4) and free
      thyroxine (FT4, by equilibrium dialysis) and markedly elevated thyroid
      stimulating hormone (TSH) concentrations supported the diagnosis of
      hypothyroidism. At necropsy, the thyroid gland was grossly enlarged and
      histologically exhibited severe, diffuse hyperplasia of the follicular
      epithelium. Gross examination of the central nervous system revealed a myelin
      deficiency, most evident in the corpus callosum. Regional distribution of
      hypomyelination was confirmed histologically, affecting the corpus callosum and,
      to a lesser degree, the corona radiata, the longitudinal fibers of the pons, the
      pyramids, and the lateral funiculi of the spinal cord. Myelin reduction was
      paralleled by axon reduction, suggesting that hypomyelination was a consequence
      of reduced axonal formation. A homozygous nonsense mutation in the thyroid
      peroxidase gene was identified in the affected puppies. The dam and a clinically
      normal litter mate were heterozygous for this mutation, confirming simple
      autosomal recessive inheritance of the disease trait. The same mutation, causing
      congenital hypothyroidism with a goiter was previously described in the Toy Fox
      Terrier breed. Given the ongoing practice of introducing the Toy Fox Terrier
      genetic background into some Rat Terrier breeding programs to obtain a smaller
      stature and the apparent relative incidence of the disorder in the 2 breeds, it
      is likely that this mutation crossed into the Rat Terrier breed from Toy Fox
      Terriers fairly recently.

PMID- 17197624
TI  - Morphometric analysis of the retina from horses infected with the Borna disease
      virus.
AB  - Borna disease (BD) is a fatal disorder of horses, often characterized by
      blindness. Although degeneration of retinal neurons has been demonstrated in a
      rat model, there are controversial data concerning whether a similar degeneration
      occurs in the retina of infected horses. To investigate whether BD may cause
      degeneration of photoreceptors and possibly of other neuronal cells at least at
      later stages of the disease, we performed a detailed quantitative morphologic
      study of retinal tissue from Borna-diseased horses. BD was diagnosed by detection
      of pathognomonic Joest-Degen inclusion bodies in the postmortem brains. Paraffin
      sections of paraformaldehyde-fixed retinae were used for histologic and
      immunohistochemical stainings. Numbers of neurons and Muller glial cells were
      counted, and neuron-to-Muller cell ratios were calculated. Among tissues from 9
      horses with BD, we found retinae with strongly altered histologic appearance as
      well as retinae with only minor changes. The neuron-to-Muller cell ratio for the
      whole retina was significantly smaller in diseased animals (8.5 +/- 0.4; P < .01)
      as compared with controls (17.6 +/- 0.8). It can be concluded that BD in horses
      causes alterations of the retinal histology of a variable degree. The study
      provides new data about the pathogenesis of BD concerning the retina and
      demonstrates that a loss of photoreceptors may explain the observed blindness in
      infected horses.

PMID- 17197625
TI  - Experimental infection of C3H/HeJ mice with the NY18 isolate of Anaplasma
      phagocytophilum.
AB  - Human granulocytic anaplasmosis (HGA), an emerging disease of public health
      concern in many areas of the world, is caused by Anaplasma phagocytophilum. Small
      animal models of A phagocytophilum in laboratory mice have been developed and
      used to study the pathogenesis of HGA. In this study, we characterized the
      pathologic changes in acute infection of C3H/HeJ mice experimentally infected
      with the NY18 isolate of A phagocytophilum. Although no clinical signs were
      noted, acute infection was associated with gross splenomegaly, microscopic
      inflammatory lesions in the lung and liver, hyperplastic lesions on the spleen,
      and clinical pathology abnormalities including neutropenia and monocytosis. This
      study emphasizes the use of well-defined animal models as a valuable tool for the
      study of A phagocytophilum infections.

PMID- 17197626
TI  - Immunohistochemical detection of protein gene product 9.5 (PGP 9.5) in canine
      epitheliotropic T-cell lymphoma (mycosis fungoides).
AB  - Protein gene product 9.5 (PGP 9.5), a ubiquitin COOH-terminal hydrolase initially
      considered specific for neural and neuroendocrine tissues, is expressed in a
      variety of epithelial and mesenchymal tumors. During immunohistochemical
      evaluation of a cutaneous epitheliotropic T-cell lymphoma (mycosis fungoides
      [MF]) in a dog, strong reactivity for PGP 9.5 was observed. This unexpected
      result prompted us to examine PGP 9.5 immunoreactivity in 13 additional cases of
      canine mycosis fungoides. All tumors were confirmed as T-cell epitheliotropic
      lymphoma by histopathology and immunohistochemistry for CD3. Eight of 14 cases
      were positive for PGP 9.5, with reactivity mainly in the cytoplasm and less
      commonly in the nucleus. One case had strong reactivity in the cell membrane,
      sometimes with concurrent paranuclear staining. Immunoreactivity did not
      correlate with location (epidermal, dermal, and adnexal) of tumor cells. Disease
      outcome did not vary between PGP 9.5-positive and negative tumors. Although PGP
      9.5 immunoreactivity in MF did not predict tumor behavior in these dogs, it has
      had prognostic value in certain human carcinomas. This unexpected staining of
      lymphocytes in mycosis fungoides with an antibody to PGP 9.5 demonstrates its
      presence in nonneuroendocrine tumors and precludes its use as the sole diagnostic
      marker in discrete cell tumors in the skin.

PMID- 17197627
TI  - An immunohistochemical and polymerase chain reaction evaluation of feline
      plasmacytic pododermatitis.
AB  - Sections of 14 skin biopsies of cats with plasmacytic pododermatitis and a
      clinical follow-up of 12-36 months were stained with a polyclonal anti
      Mycobacterium bovis (Bacille Calmette-Guerin = BCG) antibody cross-reactive to a
      broad spectrum of fungi and bacteria. All sections were negative for organisms
      within the actual footpad tissue with the anti-BCG antibody stains. Polymerase
      chain reaction (PCR) assays that amplify the DNA of Bartonella spp., Ehrlichia
      spp., Anaplasma phagocytophilum, Chlamydophila felis, Mycoplasma spp., Toxoplasma
      gondii, and feline herpesvirus 1 (FHV-1) were applied to tissue digests. DNA of
      those pathogens assessed was not amplified from tissue.

PMID- 17197628
TI  - Maxillary ameloblastic carcinoma in an Alaskan Malamute.
AB  - A 3-year-old female Alaskan Malamute was submitted to the Veterinary Teaching
      Hospital of Madrid with a mass in the right maxilla. It was ulcerated, covered by
      a yellowish infected membrane, and painful. The histologic examination showed a
      neoplastic proliferation of palisading cells distributed irregularly in cords.
      The tumor was diagnosed as an ameloblastic carcinoma because of the histologic
      signs of malignancy, the aggressive behavior, and the absence of distal
      metastasis. This is the first description of an ameloblastic carcinoma in a dog.

PMID- 17197629
TI  - Escherichia coli septicemia associated with lack of maternally acquired immunity
      in a bottlenose dolphin calf.
AB  - Stillbirth and neonatal mortality are substantial problems in captive bottlenose
      dolphins (Tursiops truncatus). The cause of these problems often is unknown. We
      report a case of Escherichia coli septicemia in a male 3-day-old bottlenose
      dolphin calf. Lesions included omphalitis, synovitis, and hepatic necrosis
      associated with the presence of Gram-negative bacilli. E. coli was isolated in
      pure culture from multiple organs. A serum gammaglobulin level of 1.5 g/L
      indicated a lack of maternally acquired immunity. The observed failure to nurse
      may have resulted from brain injury due to perinatal asphyxia. Evidence for
      perinatal asphyxia was the diffuse presence of a moderate amount of meconium in
      the lungs.

PMID- 17197630
TI  - Solitary biliary hamartoma with cholelithiasis in a domestic rabbit (Oryctolagus
      cuniculus).
AB  - Hamartomas of the liver and biliary system are extremely rare entities in both
      animals and humans. Biliary hamartomas in humans are usually multiple and
      constitute the von Meyenburg complexes. This report describes the presence of a
      large solitary mass arising from the edge of the right medial liver lobe of a
      domestic rabbit. Histologically, the mass was composed of an extensive network of
      large varying sized cystic structures lined by simple cuboidal to columnar
      epithelium within an abundant fibrous stroma. Within many of the cyst lumina were
      varying sized, pale white to greenish hard concretions identified as choleliths
      and were analyzed and found to be composed of calcium carbonate. This is the
      first known report of biliary hamartoma with cholelithiasis in rabbits.

PMID- 17197631
TI  - Histologic and ultrastructural studies of juvenile onset renal disease in four
      Rottweiler dogs.
AB  - Juvenile onset renal disease is described in 2 male and 2 female young Rottweiler
      dogs. Histologic changes in all dogs were cystic dilatation of Bowman's space,
      mesangial hypercellularity, and glomerulosclerosis. Three dogs also had
      glomerular crescents and moderate to severe interstitial fibrosis. Electron
      microscopy revealed glomerular basement membranes of variable thickness, with
      extensive splitting or lamellation of the lamina densa. These ultrastructural
      findings are similar to those found in people and in other breeds of dogs with
      inherited defects in type IV collagen.

PMID- 17197632
TI  - Mesenchymal hamartoma of the liver in a late-term equine fetus.
AB  - Mesenchymal hamartoma of the liver is a rare congenital disorder of biliary tract
      development. During the necropsy of a late-term equine fetus, a markedly enlarged
      liver of more than two times normal weight was found. Light microscopic review
      revealed that the normal hepatic parenchyma had been obliterated, replaced, and
      expanded by abnormal bile ducts surrounded by abundant, myxoid stroma. The lesion
      was diagnosed as a mesenchymal hamartoma. Small portions of the liver had
      bridging septa of fibrosis and proliferations of small-caliber abnormal bile
      ducts, resembling another congenital biliary abnormality termed congenital
      hepatic fibrosis.

PMID- 17197633
TI  - Severe granulomatous lesions in several organs from Eustrongylides larvae in a
      free-ranging dice snake, Natrix tessellata.
AB  - During an extensive study regarding the epidemiology of larval Eustrongylides
      infestation in a free-ranging endangered population of dice snakes (Natrix
      tessellata) from Histria, Romania, an adult female was euthanized to evaluate
      pathologic changes. Parasites appeared as nodules at various locations: in
      subcutaneous connective tissues, on the serosae of the intestines and liver.
      Histologic sections revealed nematode larvae surrounded by a capsule, forming a
      parasitic granuloma with 3 layers: macrophage layer, lymphocyte layer, and
      fibrous capsule. Differences between newly formed and mature granulomas consisted
      mainly in the eosinophilic infiltration. Other types of parasitic granulomas of
      reptiles are discussed in comparison with our findings.

PMID- 17197634
TI  - Fibrosing gastrointestinal leiomyositis as a cause of chronic intestinal pseudo
      obstruction in an 8-month-old dog.
AB  - An 8-month-old, female, mixed-breed dog presented to the Iowa State University
      Veterinary Teaching Hospital with a 1-month history of vomiting and diarrhea. An
      exploratory laparotomy was performed revealing markedly distended and fluid
      filled small and large intestines that were not obstructed. The clinical
      condition of the dog did not improve subsequent to exploratory surgery, and it
      was euthanized. At necropsy, both the small and large intestines were distended
      (approximately 4 cm in diameter) and fluid-filled, and the wall was thin. The
      abdominal cavity contained approximately 500 ml of a brownish clear fluid.
      Microscopic lesions of the intestines were confined to the intestinal tunica
      muscularis and muscularis mucosae and consisted of locally extensive-to-diffuse
      replacement of the smooth muscle by fibrous tissue and multifocal infiltration by
      a moderately dense mononuclear inflammatory infiltrate. A unique finding was the
      presence of similar microscopic lesions in the tunica muscularis of the urinary
      bladder and stomach.

PMID- 17197635
TI  - Fatal ulcerative and hemorrhagic typhlocolitis in a pregnant heifer associated
      with natural bovine enterovirus type-1 infection.
AB  - One 2-year-old, 7.5 months pregnant Aberdeen Angus out of a herd of 100
      apparently healthy cows, died within 10 hours of hospitalization. At necropsy,
      multiple foci of mucosal hemorrhage and ulceration were observed in the spiral
      colon and cecum. Virus isolation from intestinal lesions yielded a cytopathic
      virus, which was revealed by electron microscopy to be an approximately 27 nm,
      nonenveloped virus. Further characterization by reverse transcription-polymerase
      chain reaction (RT-PCR), sequencing of the 5'UTR and partial VP1 coding region,
      and phylogenetic analysis classified the virus isolate as bovine enterovirus type
      1 (BEV-1). No other significant pathogens were detected. This is the first report
      of BEV-1 isolated in the USA from an animal with fatal enteric disease in more
      than 20 years. Further investigation is required to determine the prevalence of
      BEV in North America and to establish the clinical relevance of this understudied
      virus.

PMID- 17197636
TI  - In vivo endothelial cell infection by Anaplasma marginale.
AB  - Anaplasma marginale has recently been shown to infect endothelial cells in vitro,
      but it remains unknown as to whether endothelial infection also occurs in vivo.
      In this report, we demonstrate through dual fluorescence microscopy that A
      marginale, detected by the monoclonal antibody ANAF16C1, co-localizes with the
      endothelial cell marker, von Willebrand factor, in tissue sections from an
      experimentally inoculated calf. The results indicate that A marginale infection
      includes endothelial cells and has implications for both pathogenesis and immune
      mechanisms.

PMID- 17197637
TI  - Verminous encephalitis in a horse produced by nematodes in the family
      protostrongylidae.
AB  - Parasitic granulomatous eosinophilic inflammation was observed in the central
      nervous system (CNS) of a 6-month-old Arabian colt from New York state.
      Inflammation was associated with eggs, larvae, and adult nematodes in the
      cerebellum. Nematodes had histological characteristics of the superfamily
      Metastrongyloidea. The presence of dorsal-spined larvae in the CNS was further
      indicative of infection with a nematode in the family Protostrongylidae.
      Infections were most compatible with Parelaphostrongylus tenuis but specific
      diagnosis was not possible. This is the first definitive report of a
      protostrongylid nematode infection in a horse.

PMID- 17197638
TI  - Disseminated Mycobacterium avium subsp. avium infection in a pet Korean squirrel
      (Sciuris vulgaris coreae).
AB  - A disseminated Mycobacterium avium subsp. avium infection was diagnosed in a pet
      Korean squirrel. Grossly, multiple small nodules in the lung, liver, spleen, and
      skin were observed. Adrenal glands were very enlarged. The only tissue exhibiting
      necrosis and calcification was a very enlarged bronchial lymph node. The
      remaining lymph nodes were slightly enlarged. Moderate ascites was also observed.
      Microscopically, a disseminated granulomatous inflammation with numerous
      lymphocytes was seen. Acid-fast bacilli were detected in macrophages, in giant
      cells, free in the interstitium, and in some lymphatic vessels, both within cells
      and free in the lumen. M. avium subsp. avium was isolated and identified by
      polymerase chain reaction-restriction endonuclease analysis.

PMID- 17197639
TI  - Are all testicular seminomas of animals in fact spermatocytic seminomas?

PMID- 17197640
TI  - Impaired defense of core temperature in aged humans during mild cold stress.
AB  - Aged humans often exhibit an impaired defense of core temperature during cold
      stress. However, research documenting this response has typically used small
      subject samples and strong cold stimuli. The purpose of this study was to
      determine the responses of young and older subjects, matched for anthropometric
      characteristics, during mild cold stress. Thirty-six young (YS; 23 +/- 1 years,
      range 18-30) and 46 older (OS; 71 +/- 1 years, range 65-89) subjects underwent a
      slow transient cold air exposure from a thermoneutral baseline, during which
      esophageal (T(es)) and mean skin temperatures (T(sk)), O(2) consumption, and skin
      blood flow (SkBF; laser-Doppler flowmetry) were measured. Cold exposure was
      terminated at the onset of visible sustained shivering. Net metabolic heat
      production (M(net)), heat debt, predicted change in midregion temperature
      (DeltaT(mid)), and tissue insulation (I(t)) were calculated. Cutaneous vascular
      conductance (CVC) was calculated as laser-Doppler flux/mean arterial pressure and
      expressed as percent change from baseline (DeltaCVC(%base)). There were no
      baseline group differences for T(es), but OS M(net) was lower (OS: 38.0 +/- 1.1;
      YS: 41.9 +/- 1.1 W . m(-2), P < 0.05). T(es) was well maintained in YS but fell
      progressively in OS (P < 0.01 for all timepoints after 35 min). The skin
      vasoconstrictor response to mild cold stress was attenuated in OS (42 +/- 3 vs.
      53 +/- 4 DeltaCVC(%base), P < 0.01). There were no group differences for T(sk) or
      I(t), while M(net) remained lower in OS (P < 0.05). The DeltaT(mid) did not
      account for the drop in T(es) in OS. Healthy aged humans failed to maintain
      T(es); however, the mechanisms underlying this response are not clear.

PMID- 17197641
TI  - Exercise can be pyrogenic in humans.
AB  - Exercise increases mean body temperature (T(body)) and cytokine concentrations in
      plasma. Cytokines facilitate PG production via cyclooxygenase (COX) enzymes, and
      PGE(2) can mediate fever. Therefore, we used a COX-2 inhibitor to test the
      hypothesis that PG-mediated pyrogenicity may contribute to the raised T(body) in
      exercising humans. In a double-blind, cross-over design, 10 males [age: 23 yr (SD
      5), Vo(2 max): 53 ml x kg(-1) x min(-1) (SD 5)] consumed rofecoxib (50 mg/day;
      NSAID) or placebo (PLAC) for 6 days, 2 wk apart. Exercising thermoregulation was
      measured on day 6 during 45-min running ( approximately 75% Vo(2 max)) followed
      by 45-min cycling and 60-min seated recovery (28 degrees C, 50% relative
      humidity). Plasma cytokine (TNF-alpha, IL-10) concentrations were measured at
      rest and 30-min recovery. T(body) was similar at rest in PLAC (35.59 degrees C)
      and NSAID (35.53 degrees C) and increased similarly during running, but became
      0.33 degrees C (SD 0.26) lower in NSAID during cycling (37.39 degrees C vs. 37.07
      degrees C; P = 0.03), and remained lower throughout recovery. Sweating was
      initiated at T(body) of approximately 35.6 degrees C in both conditions but
      ceased at higher T(body) in PLAC than NSAID during recovery [36.66 degrees C (SD
      0.36) vs. 36.39 degrees C (SD 0.27); P = 0.03]. Cardiac frequency averaged 6 x
      min(-1) higher in PLAC (P < 0.01), whereas exercising metabolic rate was similar
      (505 vs. 507 W x m(-2); P = 0.56). A modest increase in both cytokines across
      exercise was similar between conditions. COX-2 specific NSAID lowered exercising
      heat and cardiovascular strain and the sweating (offset) threshold, independently
      of heat production, indicating that PGE-mediated inflammatory processes may
      contribute to exercising heat strain during endurance exercise in humans.

PMID- 17197642
TI  - The median preoptic nucleus is involved in the facilitation of heat-escape/cold
      seeking behavior during systemic salt loading in rats.
AB  - Systemic salt loading has been reported to facilitate operant heat-escape/cold
      seeking behavior. In the present study, we hypothesized that the median preoptic
      nucleus (MnPO) would be involved in this mechanism. Rats were divided into two
      groups (n = 6 each): one group had the MnPO lesion with ibotenic acid (4.0 mug)
      and the other was the vehicle control. After subcutaneous injection (10 ml/kg) of
      either isotonic- (154 mM) or hypertonic-saline (2,500 mM), each rat was placed in
      a behavior box, where the ambient temperature was changed to 26 degrees C, 35
      degrees C, and 40 degrees C every 1 h. The position of a rat in the box and the
      body core temperature (T(core)) were monitored. A rat could trigger 0 degrees C
      air for 45 s in the 35 degrees C and 40 degrees C heat when moved in a specific
      area in the box (operant behavior). In the control group, counts of the operant
      behavior were greater (P < 0.05) in the hypertonic- than in the isotonic-saline
      injection (17 +/- 2 and 10 +/- 2 at 35 degrees C, 24 +/- 2 and 18 +/- 1 at 40
      degrees C). T(core) remained unchanged throughout the exposure, although the
      level was lower (P < 0.05) in the hypertonic- than in the isotonic-saline trial
      (36.6 +/- 0.2 degrees C and 37.4 +/- 0.1 degrees C at 26 degrees C and 36.9 +/-
      0.2 degrees C and 37.4 +/- 0.1 degrees C at 40 degrees C, respectively). However,
      in the MnPO-lesion group, counts of the behavior were similar between the
      hypertonic- and isotonic-saline injection trials (10 +/- 2 and 8 +/- 1 at 35
      degrees C, and 17 +/- 1 and 16 +/- 1 at 40 degrees C, respectively). T(core)
      increased (P < 0.05) in the heat in both trials (36.8 +/- 0.1 degrees C and 37.4
      +/- 0.1 degrees C at 26 degrees C and 37.4 +/- 0.2 degrees C and 37.8 +/- 0.2
      degrees C at 40 degrees C in the hypertonic- and isotonic-saline injection
      trials, respectively). These results may suggest that, at least in part, the MnPO
      is involved in the facilitation of heat-escape/cold-seeking behavior during
      osmotic stimulation.

PMID- 17197643
TI  - Nutrient selection through nutrigenomic approaches.

PMID- 17197644
TI  - Renin receptor expression in human adipose tissue.
AB  - Adipose tissue synthesizes all components of the renin-angiotensin system. The
      renin receptor (RenR) is able, on renin binding, to increase its efficiency to
      generate angiotensin I from angiotensinogen. We demonstrate that RenR is
      specifically synthesized in the stromal portion of human adipose tissue in both
      isolated interadipocyte stromal cells and in stromal areas. RenR is expressed at
      the periphery of cells, strongly suggesting a membranal localization. RenR
      protein expression in primary cultures of human stromal cells decreased
      significantly during differentiation, whereas RenR mRNA levels did not change,
      demonstrating that RenR was expressed in both preadipocyte and nonpreadipocyte
      cells, and was regulated at a posttranscriptional level. Double-labeling
      immunohistochemistry of human adipose tissue sections revealed that RenR was
      colocalized with renin, whereas incubation of 3T3-L1, a preadipocyte cell line,
      with renin stimulated the phosphorylation state of the intracellular signaling
      pathway ERK 1/2, and short exposure of human adipose stromal cells in primary
      culture to renin was followed by a long-lasting dose-dependent increase of
      angiotensin I generation, indicating that adipose RenR is functional. We show,
      using a large set of human adipose tissue biopsies, that RenR expression was
      increased in visceral compared with subcutaneous adipose tissue of lean and obese
      patients. Taken together with our finding that RenR was colocalized with
      plasminogen activator inhibitor type 1, the main inhibitor of the fibrinolytic
      system in visceral adipose tissue, the above-mentioned data suggest that RenR
      plays a role in obesity-induced visceral adipose tissue accumulation and its
      accompanying cardiovascular complications.

PMID- 17197645
TI  - Hypothalamic expression of thyroid hormone-activating and -inactivating enzyme
      genes in relation to photorefractoriness in birds and mammals.
AB  - Photorefractoriness is the insensitivity of gonadal development to the
      stimulatory effects of long photoperiods in birds and to the inhibitory effects
      of short photoperiods in small mammals. Its molecular mechanism remains unknown.
      Recently, it has been shown that reciprocal expression of thyroid hormone
      activating enzyme [type 2 deiodinase (Dio2)] and -inactivating enzyme [type 3
      deiodinase (Dio3)] genes in the mediobasal hypothalamus is critical for
      photoperiodically induced gonadal growth. Since thyroid hormones are required not
      only for photoinduction, but also for the induction of photorefractoriness, we
      examined the expression of these genes in relation to photorefractoriness in
      birds and mammals. Transfer of birds to long photoperiods induced strong
      expression of Dio2. This was maintained in tree sparrow when they later became
      photorefractory, but decreased somewhat in quail. In hamsters, transfer to long
      photoperiods also induced strong expression of Dio2. High values were not
      maintained under long photoperiods, and, indeed, expression decreased at the same
      rate as in animals transferred to short photoperiods. There was no renewed
      expression of Dio2 associated with testicular growth as animals became refractory
      to short photoperiods. Expression of Dio3 was high under short photoperiods and
      low under long photoperiods in all the animals examined, except for the short
      photoperiod-refractory hamsters. Our present study revealed complex regulation of
      deiodinase genes in the photoinduction and photorefractory processes in birds and
      mammals. These gene changes may be involved in the regulation of
      photorefractoriness, as well as photoinduction.

PMID- 17197647
TI  - Nocardia nova as the causative agent in spondylodiscitis and psoas abscess.
AB  - We describe here the first case of Nocardia nova spondylodiscitis accompanied by
      a psoas abscess due to spreading from pulmonary nocardiosis. Nocardia was
      cultured from all affected sites. After 1 year of an appropriate antimicrobial
      therapy and a surgical drainage of the abscess that was required, the patient's
      clinical condition had improved.

PMID- 17197648
TI  - Gene-environment interplay in attention-deficit hyperactivity disorder and the
      importance of a developmental perspective.
AB  - Attention-deficit hyperactivity disorder (ADHD) varies in its clinical
      presentation and course. Susceptibility gene variants for ADHD and associated
      antisocial behaviour are being identified with emerging evidence of gene
      environment interaction. Genes and environmental factors that influence the
      origins of disorder are not necessarily the same as those that contribute to its
      course and outcome.

PMID- 17197649
TI  - Adult attention-deficit hyperactivity disorder: recognition and treatment in
      general adult psychiatry.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common disorder affecting
      children and adults. Many young people treated with stimulants, as well as those
      in whom ADHD went unrecognised in childhood, need treatment as adults. Stimulants
      and atomoxetine effectively reduce ADHD symptoms at all ages and should be a
      standard treatment in general adult psychiatric practice.

PMID- 17197650
TI  - Mood disorders and migration: meta-analysis.
AB  - BACKGROUND: Migration is a risk factor for the development of schizophrenia.
      AIMS: To examine whether migration is also a risk factor for bipolar affective
      disorder, unipolar depressive disorder and mood disorders in general. METHOD:
      Medline was searched for population-based incidence studies concerning mood
      disorders among migrants and mean relative risks were computed using a mixed
      effects statistical model. RESULTS: Only a few studies of unipolar depressive
      disorder were retrieved. The mean relative risk of developing bipolar affective
      disorder among migrants was 2.47 (95% CI 1.33-4.59). However, after excluding
      people of African-Caribbean origin in the UK this risk was no longer
      significantly increased. The mean relative risk of mood disorders of unspecified
      polarity was 1.25 (95% CI 1.04-1.49) and that of any mood disorder was 1.38 (95%
      CI 1.17-1.62). CONCLUSIONS: There is no conclusive evidence for a large increase
      in the risk of mood disorders associated with migration.

PMID- 17197652
TI  - Adolescent-onset psychosis: prevalence, needs and service provision.
AB  - BACKGROUND: Little is known of the epidemiology and care needs of people with
      adolescent-onset psychosis. AIMS: To examine prevalence and the cross-sectional
      disability, needs and service provision for adolescent-onset psychosis in areas
      of central Scotland with a total population of 1.75 million. METHOD: We
      identified and contacted 103 young people using an opt-out research design. Fifty
      three participants and their carers and keyworkers were interviewed using a
      modified version of the Cardinal Needs Schedule. RESULTS: The 3-year prevalence
      was 5.9 per 100,000 general population. Twenty-one (20%) adolescents were not in
      contact with mental health services; 80% of first admissions were to adult acute
      psychiatric wards. Those interviewed had high levels of morbidity: 29 (55%) had
      serious to pervasive impairment of functioning; there were relatively high levels
      of side-effects, negative symptoms, anxiety, occupational, friendship and family
      difficulties. Care provision was better for'clinical'than for'social'domains; 20%
      had five or more unmet needs; 17% had at least one intractable problem.
      CONCLUSIONS: This low-prevalence disorder requires an assertive multi-agency
      approach in the context of a national planning framework.

PMID- 17197651
TI  - Psychosocial interventions following self-harm: systematic review of their
      efficacy in preventing suicide.
AB  - BACKGROUND: With almost a million people dying by suicide worldwide each year,
      reducing the rate of suicidal behaviour is a priority in many countries. AIMS: To
      examine whether additional psychosocial interventions following an episode of
      self-harm reduce the likelihood of subsequent suicide. METHOD: We conducted a
      systematic review and meta-analysis of data from randomised controlled trials of
      interventions for people following self-harm. Likelihood of suicide was compared
      by calculating the pooled root difference in suicide rate with 95% confidence
      intervals. RESULTS: We obtained suicide data from 18 studies with a total
      population of 3918. Eighteen suicides occurred among people offered active
      treatment and 19 among those offered standard care (pooled root difference in
      suicide rate 0.0,95% CI -0.03 to 0.03). The overall rate of suicide among people
      participating in trials was similar to that reported in observational studies of
      people who self-harm. CONCLUSIONS: Results of this meta-analysis do not provide
      evidence that additional psychosocial interventions following self-harm have a
      marked effect on the likelihood of subsequent suicide.

PMID- 17197653
TI  - Mental ill-health in adults with intellectual disabilities: prevalence and
      associated factors.
AB  - BACKGROUND: Reported prevalence of mental ill-health among adults with
      intellectual disabilities ranges from 7 to 97%, owing to methodological
      limitations. Little is known about associations. AIMS: To determine the
      prevalence of mental ill-health in adults with intellectual disabilities and to
      investigate factors independently associated with it. METHOD: Population-based
      study (n=1023) with comprehensive individual assessments modelled using
      regression analyses. RESULTS: Point prevalence of mental ill-health was 40.9%
      (clinical diagnoses), 35.2% (DC-LD), 16.6% (ICD-10-DCR) and 15.7% (DSM-IV-TR).
      The most prevalent type was problem behaviours. Mental ill-health was associated
      with more life events, female gender, type of support, lower ability, more
      consultations, smoking, incontinence, not having severe physical disabilities and
      not having immobility; it was not associated with deprived areas, no occupation,
      communication impairment, epilepsy, hearing impairment or previous institutional
      residence. CONCLUSIONS: This investigation informs further longitudinal study,
      and development of appropriate interventions, public health strategy and policy.
      ICD-10-DCR and DSM-IV-TR undercount mental ill-health in this population compared
      with DC-LD.

PMID- 17197654
TI  - Life stress and depression in a tribal area of Pakistan.
AB  - BACKGROUND: Depression is common in Pakistan but no research on this subject has
      been reported from the North West Frontier Province (NWFP), host to numerous
      Afghan refugees. AIMS: To measure depressive symptoms and associated features in
      a population-based sample. METHOD: A Pushto translation of the Self Reporting
      Questionnaire (SRQ) was administered to 471 adults living in a village in one of
      the federally administered tribal areas. Respondents were also assessed with a
      life events checklist for social problems, a social support questionnaire and the
      Brief Disability Questionnaire. RESULTS: Sixty per cent (95/158) of women and 45%
      (140/313) of men scored 9 or more on the SRQ. High SRQ score was associated with
      few years of education, higher social problem score, less social support and
      greater disability. High social problem score was the strongest correlate.
      CONCLUSIONS: This population reports more depressive symptoms than other
      communities in Pakistan and this probably reflects the very high degree of social
      stress experienced in the NWFP, which has been affected by years of turmoilin
      neighbouring Afghanistan.

PMID- 17197655
TI  - Psychiatric and psychosocial predictors of substance use disorders among
      adolescents: longitudinal study.
AB  - BACKGROUND: Few studies have prospectively examined psychosocial and psychiatric
      predictors of adolescent substance use disorders simultaneously. AIMS: To
      identify psychosocial and psychiatric predictors of substance use disorders in
      adolescence. METHOD: School children aged 12 years (s.d.=0.3) free from any
      substance use disorder at grade 7 (n=428) were assessed in three consecutive
      years, using a standardised psychiatric interview. Their baseline psychosocial
      information was also collected. The outcome was the onset age of a substance use
      disorder. The Cox regression model was used for data analysis. RESULTS: The most
      significant predictive factors for adolescent substance use disorder included
      male gender, attention-deficit hyperactivity disorder, conduct disorder and
      sibling use of tobacco. Three protective factors against such morbidity included
      living in a household with two parents, a good academic grade at grade 7 and
      objection to the use of substances. CONCLUSIONS: Early intervention for
      disruptive behaviour disorders and specific psychosocial risk factors might
      prevent substance use disorders in early adolescence.

PMID- 17197656
TI  - Efficacy of the Community Re-Entry Module for patients with schizophrenia in
      Beijing, China: outcome at 2-year follow-up.
AB  - BACKGROUND: Few psychosocial interventions have been developed in China that are
      suitable for use in the community. AIMS: To evaluate the effectiveness of the
      Chinese version of the Community Re-Entry Module (CRM; a module of a
      standardised, structured social skills training programme devised at the
      University of California, Los Angeles) for patients with schizophrenia compared
      with standard group psychoeducation. METHOD: Patients with schizophrenia (n=103)
      were randomly allocated to CRM or psychoeducation groups and followed up for 24
      months. Outcome measures included social functioning, psychiatric symptoms,
      insight, re-employment, relapse and re-hospitalisation rates. RESULTS: The CRM
      group significantly improved in terms of social functioning, insight and
      psychiatric symptoms compared with the psychoeducation group; the re-employment
      rate was significantly higher and relapse and rehospitalisation rates were
      significantly lower in the CRM group. CONCLUSIONS: The findings support the
      feasibility and effectiveness of CRM as a psychosocial intervention for Chinese
      patients with schizophrenia in the community.

PMID- 17197657
TI  - Competition for neuronal resources: how hallucinations make themselves heard.
AB  - BACKGROUND: Hallucinations are perceptions in the absence of a corresponding
      external sensory stimulus. However, during auditory verbal hallucinations,
      activation of the primary auditory cortex has been described. AIMS: The objective
      of this study was to investigate whether this activation of the auditory cortex
      contributes essentially to the character of hallucinations and attributes them to
      alien sources, or whether the auditory activation is a sign of increased general
      auditory attention to external sounds. METHOD: The responsiveness of the auditory
      cortex was investigated by auditory evoked potentials (N100) during the
      simultaneous occurrence of hallucinations and external stimuli. Evoked potentials
      were computed separately for periods with and without hallucinations; N100 power,
      topography and brain electrical sources were analysed. RESULTS: Hallucinations
      lowered the N100 amplitudes and changed the topography, presumably due to a
      reduced left temporal responsivity. CONCLUSIONS: This finding indicates
      competition between auditory stimuli and hallucinations for physiological
      resources in the primary auditory cortex. The abnormal activation of the primary
      auditory cortex may thus be a constituent of auditory hallucinations.

PMID- 17197659
TI  - Distribution of CORE-OM scores in a general population, clinical cut-off points
      and comparison with the CIS-R.
AB  - BACKGROUND: Although measures of psychopathology are designed for use in clinical
      populations, their meaning derives from comparison with normal populations. AIMS:
      To compare the distribution of scores on the Clinical Outcomes in Routine
      Evaluation-Outcome Measure (CORE-OM) from a general population sample with the
      distribution in an aggregated clinical sample to derive recommended cut-off
      points for determining clinical significance. METHOD: The CORE-OM general
      population sample was based on a weighted subsample of participants in the
      psychiatric morbidity follow-up survey who completed valid CORE-OM forms
      following their interview (effective n=535). RESULTS: Comparison of the CORE-OM
      general population sample with a clinical sample aggregated from previous studies
      (n=10761) yielded a cut-off score of 9.9 on the 0-40 scale of the CORE-OM. The
      CORE-OM was highly correlated (r=0.77) with the Clinical Interview Schedule
      Revised, supporting convergent validity. CONCLUSIONS: We recommend rounding the
      CORE-OM cut-off score to 10. However, cut-off scores must be used thoughtfully
      and adjusted to fit context and purpose.

PMID- 17197658
TI  - Changes in regional cerebral blood flow during acute electroconvulsive therapy in
      patients with depression: positron emission tomographic study.
AB  - BACKGROUND: Although electroconvulsive therapy (ECT) is widely used to treat
      psychiatric disorders such as depression, its precise neural mechanisms remain
      unknown. AIMS: To investigate the time course of changes in cerebral blood flow
      during acute ECT. METHOD: Cerebral blood flow was quantified serially prior to,
      during and after acute ECT in six patients with depression under anaesthesia
      using [(15)O]H(2)O positron emission tomography (PET). RESULTS: Cerebral blood
      flow during ECT increased particularly in the basal ganglia, brain-stem,
      diencephalon, amygdala, vermis and the frontal, temporal and parietal cortices
      compared with that before ECT. The flow increased in the thalamus and decreased
      in the anterior cingulate and medial frontal cortex soon after ECT compared with
      that before ECT. CONCLUSIONS: These results suggest a relationship between the
      centrencephalic system and seizure generalisation. Further, they suggest that
      some neural mechanisms of action of ECT are mediated via brain regions including
      the anterior cingulate and medial frontal cortex and thalamus.

PMID- 17197660
TI  - Perceived discrimination and psychological distress in Sweden.
AB  - There is lack of evidence on the health effects of perceived discrimination. We
      analysed the association between perceived discrimination and psychological
      distress, and whether socio-economic disadvantage explains this association in
      15,406 men and 17,922 women in Sweden during 2004. After adjustment for age and
      long-term illness, frequent experiences of discrimination were associated with
      increased likelihood of psychological distress. Socio-economic disadvantage
      explained about 25% of this association.

PMID- 17197661
TI  - Contribution of low- and middle-income countries to research published in leading
      general psychiatry journals, 2002-2004.
AB  - We aimed to describe the contribution of low- and middle-income (LAMI) countries
      to leading general psychiatric journals. We reviewed original research published
      over a 3-year period (2002-2004) in the six highest-impact general psychiatry
      journals and contacted editorial offices to gather data on country of origin of
      submitted and accepted articles. Only 3.7% of published research emerges from
      these less affluent countries, which account for over 80% of the global
      population. Compared with the findings of a similar review of the period 1996
      1998, there has been little change. The three European journals had a higher
      representation than the three American journals. The proportion of psychiatrists
      in a country was associated with that country's research output. As much as 50%
      of the research from LAMI countries is led by authors from high-income countries.
      The proportion of submissions from LAMI countries was very low, and articles from
      them were more frequently rejected. Strengthening the research capacity of these
      countries and reviewing the editorial policies of leading journals can help
      increase the international representation of LAMI countries in psychiatric
      research.

PMID- 17197663
TI  - Suicide trends and antidepressants.

PMID- 17197665
TI  - Cognitive-behavioural therapy for avoidant personality disorder.

PMID- 17197667
TI  - Anti-phospholipid antibodies, neuroleptic treatment and cardiovascular morbidity.

PMID- 17197668
TI  - Doctors: automatons, technicians, or knowledge brokers?

PMID- 17197669
TI  - Gender bias in research: how does it affect evidence based medicine?

PMID- 17197670
TI  - Ankle Brachial Pressure Index: identifying cardiovascular risk and improving
      diagnostic accuracy.

PMID- 17197671
TI  - Precision and the alienating language of health care.

PMID- 17197672
TI  - The language of health care.

PMID- 17197673
TI  - The alienating language of health care.

PMID- 17197674
TI  - The British Royal Commission on Tuberculosis.

PMID- 17197675
TI  - Chronic fatigue syndrome.

PMID- 17197676
TI  - Walking and cycling transport safety.

PMID- 17197677
TI  - Cycling is not more dangerous than walking.

PMID- 17197678
TI  - Open peer review: a route to democracy.

PMID- 17197679
TI  - Funding and the NEJM.

PMID- 17197680
TI  - Seeking consensus by formal methods: a health warning.

PMID- 17197681
TI  - What is the Healthcare Commission trying to achieve?

PMID- 17197682
TI  - Lineages of language and the diagnosis of asthma.
AB  - Asthma, wheeze and cough are words with profoundly differing histories,
      etymologies and meanings. Yet their medical usage today is clustered around the
      diagnosis and management of a single disease. Hitherto, asthma has been a
      clinical diagnosis but wheeze, cough and asthma now are key terms in cross
      cultural questionnaire surveys which seek information on asthma prevalence. In
      this essay, we examine differences in the linguistic properties of terms likely
      to be relevant to interpreting large-scale variations in asthma prevalence
      uncovered by questionnaires. We show how etymologically distinct each term is:
      while asthma and cough each share semantic congruencies across six European
      languages, albeit for different reasons, there is less congruence across these
      languages for the term wheeze. The medical meanings of all three terms contrast
      with meanings revealed by the non-medical usage of all three terms, which are
      highly figurative. Linguistic considerations indicate that interpretation of
      international questionnaires that phrase questions in terms of cough, asthma and
      their derivatives are likely to be more reliable for the purposes of comparing
      prevalence than those which deploy questions phrased in terms of wheeze.

PMID- 17197683
TI  - Euthanasia and suicide in antiquity: viewpoint of the dramatists and
      philosophers.

PMID- 17197684
TI  - USAID's health challenge: improving US foreign assistance.

PMID- 17197685
TI  - The UK Department for International Development's new target strategy paper for
      health: a critical balancing act.

PMID- 17197686
TI  - Bufala spotting, part one: assessing research papers.

PMID- 17197687
TI  - Chronic kidney disease in primary care.
AB  - It has been estimated that chronic kidney disease (CKD) affects about one in 200
      of the population in the UK. There is an increased awareness of the need to
      identify patients in primary care with CKD at an earlier stage, so that
      treatments can be initiated to delay progression and prevent complications and
      appropriate nephrological referral can be made. In this article we will review
      how measures to identify patients with CKD can improve its management.

PMID- 17197688
TI  - A systematic review of cognition in homeless children and adolescents.
AB  - Objectives The cognitive function of homeless children and adolescents may be
      overlooked, albeit understandably, when societal interventions focus on their
      immediate housing needs. Nevertheless, homelessness might be hypothesized to
      carry many risks for the developing mind and brain. We wanted to discover whether
      this hypothesis had been tested previously. Design A systematic review to examine
      whether cognitive impairments were reported in homeless children and adolescents.
      Setting Objective, systematic review of standard databases, examined by key word
      searches. Participants Children and adolescents. Main outcome measures Formal
      assessments of cognition. Results We found that in spite of there being many
      homeless children in the world, fewer than 2000 have been assessed cognitively
      and reported in the literature. Yet when compared with those who are domiciled,
      these children tend to have lower intellectual functioning and decreased academic
      achievement. Furthermore, adolescents evince cognitive impairments in the
      contexts of drug, physical, and sexual abuse. Conclusions We suggest that
      cognitive and mental health screening be incorporated into those intervention
      programs deployed to facilitate societal reintegration of homeless children and
      adolescents.

PMID- 17197689
TI  - Hypocalcaemia in a patient with congenital heart disease.

PMID- 17197690
TI  - Ibn Hindu and the science of medicine.

PMID- 17197691
TI  - What is the value of an interview?

PMID- 17197692
TI  - Invited commentary.

PMID- 17197693
TI  - Invited commentary: the meanings of autonomy for physical therapy.

PMID- 17197695
TI  - On "effect of bracing..." Lenssinck et al Phys Ther 2005;85:1329-1339.

PMID- 17197696
TI  - A new membrane-bound cytochrome c works as an electron donor to the
      photosynthetic reaction center complex in the purple bacterium, Rhodovulum
      sulfidophilum.
AB  - A new type of membrane-bound cytochrome c was found in a marine purple
      photosynthetic bacterium, Rhodovulum sulfidophilum. This cytochrome c was
      significantly accumulated in cells growing under anaerobic photosynthetic
      conditions and showed an apparent molecular mass of approximately 100 kDa when
      purified and analyzed by SDS-PAGE. The midpoint potential of this cytochrome c
      was 369 mV. Flash-induced kinetic measurements showed that this new cytochrome c
      can work as an electron donor to the photosynthetic reaction center. The gene
      coding for this cytochrome c was cloned and analyzed. The deduced molecular mass
      was nearly equal to 50 kDa. Its C-terminal heme-containing region showed the
      highest sequence identity to the water-soluble cytochrome c(2), although its
      predicted secondary structure resembles that of cytochrome c(y). Phylogenetic
      analyses suggested that this new cytochrome c has evolved from cytochrome c(2).
      We, thus, propose its designation as cytochrome c(2m). Mutants lacking this
      cytochrome or cytochrome c(2) showed the same growth rate as the wild type.
      However, a double mutant lacking both cytochrome c(2) and c(2m) showed no growth
      under photosynthetic conditions. It was concluded that either the membrane-bound
      cytochrome c(2m) or the water-soluble cytochrome c(2) work as a physiological
      electron carrier in the photosynthetic electron transfer pathway of Rvu.
      sulfidophilum.

PMID- 17197697
TI  - Interleukin-1 (IL-1)-induced TAK1-dependent Versus MEKK3-dependent NFkappaB
      activation pathways bifurcate at IL-1 receptor-associated kinase modification.
AB  - Interleukin-1 (IL-1) receptor-associated kinase (IRAK) is phosphorylated after it
      is recruited to the receptor, subsequently ubiquitinated, and eventually degraded
      upon IL-1 stimulation. Although a point mutation changing lysine 134 to arginine
      (K134R) in IRAK abolished IL-1-induced IRAK ubiquitination and degradation,
      mutations of serines and threonines adjacent to lysine 134 to alanines ((S/T)A
      (131-144)) reduced IL-1-induced IRAK phosphorylation and abolished IRAK
      ubiquitination. Through the study of these IRAK modification mutants, we
      uncovered two parallel IL-1-mediated signaling pathways for NFkappaB activation,
      TAK1-dependent and MEKK3-dependent, respectively. These two pathways bifurcate at
      the level of IRAK modification. The TAK1-dependent pathway leads to IKKalpha/beta
      phosphorylation and IKKbeta activation, resulting in classical NFkappaB
      activation through IkappaBalpha phosphorylation and degradation. The TAK1
      independent MEKK3-dependent pathway involves IKKgamma phosphorylation and
      IKKalpha activation, resulting in NFkappaB activation through IkappaBalpha
      phosphorylation and subsequent dissociation from NFkappaB but without
      IkappaBalpha degradation. These results provide significant insight to our
      further understanding of NFkappaB activation pathways.

PMID- 17197698
TI  - Direct interaction between USF and SREBP-1c mediates synergistic activation of
      the fatty-acid synthase promoter.
AB  - To understand the molecular mechanisms underlying transcriptional activation of
      fatty-acid synthase (FAS), we examined the relationship between upstream
      stimulatory factor (USF) and SREBP-1c, two transcription factors that we have
      shown previously to be critical for FAS induction by feeding/insulin. Here, by
      using a combination of tandem affinity purification and coimmunoprecipitation, we
      demonstrate, for the first time, that USF and SREBP-1 interact in vitro and in
      vivo. Glutathione S-transferase pulldown experiments with various USF and sterol
      regulatory element-binding protein (SREBP) deletion constructs indicate that the
      basic helix-loop-helix domain of USF interacts directly with the basic helix-loop
      helix and an N-terminal region of SREBP-1c. Furthermore, cotransfection of USF
      and SREBP-1c with an FAS promoter-luciferase reporter construct in Drosophila SL2
      cells results in highly synergistic activation of the FAS promoter. We also show
      similar cooperative activation of the mitochondrial glycerol-3-phosphate
      acyltransferase promoter by USF and SREBP-1c. Chromatin immunoprecipitation
      analysis of mouse liver demonstrates that USF binds constitutively to the
      mitochondrial glycerol 3-phosphate acyltransferase promoter during
      fasting/refeeding in vivo, whereas binding of SREBP-1 is observed only during
      refeeding, in a manner identical to that of the FAS promoter. In addition, we
      show that the synergy we have observed depends on the activation domains of both
      proteins and that mutated USF or SREBP lacking the N-terminal activation domain
      could inhibit the transactivation of the other. Closely positioned E-boxes and
      sterol regulatory elements found in the promoters of several lipogenic genes
      suggest a common mechanism of induction by feeding/insulin.

PMID- 17197699
TI  - Structure and regulation of the human Nek2 centrosomal kinase.
AB  - The dimeric Ser/Thr kinase Nek2 regulates centrosome cohesion and separation
      through phosphorylation of structural components of the centrosome, and aberrant
      regulation of Nek2 activity can lead to aneuploid defects characteristic of
      cancer cells. Mutational analysis of autophosphorylation sites within the kinase
      domain identified by mass spectrometry shows a complex pattern of positive and
      negative regulatory effects on kinase activity that are correlated with effects
      on centrosomal splitting efficiency in vivo. The 2.2-A resolution x-ray structure
      of the Nek2 kinase domain in complex with a pyrrole-indolinone inhibitor reveals
      an inhibitory helical motif within the activation loop. This helix presents a
      steric barrier to formation of the active enzyme and generates a surface that may
      be exploitable in the design of specific inhibitors that selectively target the
      inactive state. Comparison of this "auto-inhibitory" conformation with similar
      arrangements in cyclin-dependent kinase 2 and epidermal growth factor receptor
      kinase suggests a role for dimerization-dependent allosteric regulation that
      combines with autophosphorylation and protein phosphatase 1c phosphatase activity
      to generate the precise spatial and temporal control required for Nek2 function
      in centrosomal maturation.

PMID- 17197700
TI  - Identification of the HIV-1 gp41 core-binding motif in the scaffolding domain of
      caveolin-1.
AB  - The human immunodeficiency virus, type 1 (HIV-1) gp41 core plays an important
      role in fusion between viral and target cell membranes. A single chain
      polypeptide, N36(L8)C34, which forms a six-helix bundle in physiological
      solution, can be used as a model of gp41 core. Here we identified from a 12-mer
      phage peptide library a positive phage clone displaying a peptide sequence with
      high binding activity to the HIV-1 gp41 core. The peptide sequence contains a
      putative gp41-binding motif, PhiXXXXPhiXPhi (X is any amino acid residue, and Phi
      is any one of the aromatic amino acid residues Trp, Phe, or Tyr). This motif also
      exists in the scaffolding domain of caveolin-1 (Cav-1), a known gp41-binding
      protein. Cav-1-(61-101) and Cav-1-(82-101), two recombinant fusion proteins
      containing the Cav-1 scaffolding domain, bound significantly to the gp41
      expressed in mammalian cells and interacted with the polypeptide N36(L8)C34.
      These results suggest that the scaffolding domain of Cav-1 may bind to the gp41
      core via the motif. This interaction may be essential for formation of fusion
      pore or endocytosis of HIV-1 and affect the pathogenesis of HIV-1 infection.
      Further characterization of the gp41 core-binding motifs may shed light on the
      alternative mechanism by which HIV-1 enters into the target cell.

PMID- 17197701
TI  - Electrostatic association of glutathione transferase to the nuclear membrane.
      Evidence of an enzyme defense barrier at the nuclear envelope.
AB  - The possible nuclear compartmentalization of glutathione S-transferase (GST)
      isoenzymes has been the subject of contradictory reports. The discovery that the
      dinitrosyl-diglutathionyl-iron complex binds tightly to Alpha class GSTs in rat
      hepatocytes and that a significant part of the bound complex is also associated
      with the nuclear fraction (Pedersen, J. Z., De Maria, F., Turella, P., Federici,
      G., Mattei, M., Fabrini, R., Dawood, K. F., Massimi, M., Caccuri, A. M., and
      Ricci, G. (2007) J. Biol. Chem. 282, 6364-6371) prompted us to reconsider the
      nuclear localization of GSTs in these cells. Surprisingly, we found that a
      considerable amount of GSTs corresponding to 10% of the cytosolic pool is
      electrostatically associated with the outer nuclear membrane, and a similar
      quantity is compartmentalized inside the nucleus. Mainly Alpha class GSTs, in
      particular GSTA1-1, GSTA2-2, and GSTA3-3, are involved in this double modality of
      interaction. Confocal microscopy, immunofluorescence experiments, and molecular
      modeling have been used to detail the electrostatic association in hepatocytes
      and liposomes. A quantitative analysis of the membrane-bound Alpha GSTs suggests
      the existence of a multilayer assembly of these enzymes at the outer nuclear
      envelope that could represent an amazing novelty in cell physiology. The
      interception of potentially noxious compounds to prevent DNA damage could be the
      possible physiological role of the perinuclear and intranuclear localization of
      Alpha GSTs.

PMID- 17197703
TI  - Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1.
AB  - Sir2 (silent information regulator 2) is an NAD(+)-dependent histone deacetylase
      that contributes to longevity in yeast. SIRT1, a mammalian Sir2 ortholog,
      deacetylates histones and various transcription factors, including p53, FOXO
      proteins, and peroxisome proliferator-activated receptor-gamma. We found that its
      subcellular localization varied in different tissues of the adult mouse. Some
      subsets of neurons predominantly expressed SIRT1 in the cytoplasm, but ependymal
      cells expressed it in both the nucleus and cytoplasm. On the other hand,
      spermatocytes expressed SIRT1 only in the nucleus. Cardiomyocytes in the day 12.5
      mouse embryo expressed SIRT1 exclusively in the nucleus, but in the adult heart,
      they expressed it in both the cytoplasm and nucleus. C2C12 myoblast cells
      expressed SIRT1 in the nucleus, but it localized to the cytoplasm after
      differentiation. LY294002, an inhibitor of phosphoinositide 3-hydroxykinase,
      strongly inhibited the nuclear localization of SIRT1 in undifferentiated C2C12
      cells. In a heterokaryon assay, SIRT1 shuttled between the nucleus and cytoplasm,
      and leptomycin B, an inhibitor of CRM1-mediated nuclear exportation, inhibited
      this shuttling. Two nuclear localization signals and two nuclear export signals
      were identified by deletion and site-directed mutation analyses. Overexpressed
      nuclear (but not cytoplasmic or dominant-negative) SIRT1 enhanced the
      deacetylation of histone H3 in C2C12 cells. Moreover, only the nuclear form
      suppressed the apoptosis of C2C12 cells induced by antimycin A, an oxidative
      stressor. These findings indicate that nucleocytoplasmic shuttling is a novel
      regulatory mechanism of SIRT1, which may participate in differentiation and in
      inhibition of cell death.

PMID- 17197702
TI  - Glutathione transferases sequester toxic dinitrosyl-iron complexes in cells. A
      protection mechanism against excess nitric oxide.
AB  - It is now well established that exposure of cells and tissues to nitric oxide
      leads to the formation of a dinitrosyl-iron complex bound to intracellular
      proteins, but little is known about how the complex is formed, the identity of
      the proteins, and the physiological role of this process. By using EPR
      spectroscopy and enzyme activity measurements to study the mechanism in
      hepatocytes, we here identify the complex as a dinitrosyl-diglutathionyl-iron
      complex (DNDGIC) bound to Alpha class glutathione S-transferases (GSTs) with
      extraordinary high affinity (K(D) = 10(-10) m). This complex is formed
      spontaneously through NO-mediated extraction of iron from ferritin and
      transferrin, in a reaction that requires only glutathione. In hepatocytes, DNDGIC
      may reach concentrations of 0.19 mm, apparently entirely bound to Alpha class
      GSTs, present in the cytosol at a concentration of about 0.3 mm. Surprisingly,
      about 20% of the dinitrosyl-glutathionyl-iron complex-GST is found to be
      associated with subcellular components, mainly the nucleus, as demonstrated in
      the accompanying paper (Stella, L., Pallottini, V., Moreno, S., Leoni, S., De
      Maria, F., Turella, P., Federici, G., Fabrini, R., Dawood, K. F., Lo Bello, M.,
      Pedersen, J. Z., and Ricci, G. (2007) J. Biol. Chem. 282, 6372-6379). DNDGIC is a
      potent irreversible inhibitor of glutathione reductase, but the strong complex
      GST interaction ensures full protection of glutathione reductase activity in the
      cells, and in vitro experiments show that damage to the reductase only occurs
      when the DNDGIC concentration exceeds the binding capacity of the intracellular
      GST pool. Because Pi class GSTs may exert a similar role in other cell types, we
      suggest that specific sequestering of DNDGIC by GSTs is a physiological
      protective mechanism operating in conditions of excessive levels of nitric oxide.

PMID- 17197704
TI  - The influence of insertion of a critical residue (Arg356) in structure and
      bioluminescence spectra of firefly luciferase.
AB  - The firefly bioluminescence reaction, which uses luciferin, Mg-ATP, and molecular
      oxygen to yield an electronically excited oxyluciferin, is carried out by
      luciferase and visible light is emitted. The bioluminescence color of firefly
      luciferases is determined by the luciferase structure and assay conditions. Among
      different beetle luciferases, those from Phrixothrix railroad worm emit either
      yellow or red bioluminescence colors. Sequence alignment analysis shows that the
      red-emitter luciferase from Phrixothrix hirtus has an additional Arg residue at
      353, which is absent in firefly luciferases. We report here the construction and
      purification of a mutant at residue Arg(356), which is not conserved in beetle
      luciferases. By insertion of an additional residue (Arg(356)) using site-specific
      insertion mutagenesis in a green-emitter luciferase (Lampyris turkestanicus) the
      color of emitted light was changed to red and the optimum temperature of activity
      was also increased. Insertion of this Arg in an important flexible loop showed
      changes of the bioluminescence color and the luciferase reaction took place with
      relatively retention of its basic kinetic properties such as Km and relative
      activity. Comparison of native and mutant luciferases using homology modeling
      reveals a significant conformational change of the flexible loop in the red
      mutant. Movement of flexible loop brought about a new ionic interaction
      concomitant with a change in polarity of the emitter site, thereby leading to red
      emission. It is worthwhile to note that the increased optimum temperature and
      emission of red light might make mutant luciferase a suitable reporter for the
      study of gene expression and bioluminescence imaging.

PMID- 17197705
TI  - The transcriptional repressor GFI-1 antagonizes PU.1 activity through protein
      protein interaction.
AB  - Mice lacking the zinc finger transcriptional repressor protein GFI-1 are
      neutropenic. These mice generate abnormal immature myeloid cells exhibiting
      characteristics of both macrophages and granulocytes. Furthermore, Gfi-1(-/-)
      mice are highly susceptible to bacterial infection. Interestingly, Gfi-1(-/-)
      myeloid cells overexpress target genes of the PU.1 transcription factor such as
      the macrophage colony-stimulating factor receptor and PU.1 itself. We therefore
      determined whether GFI-1 modulates the transcriptional activity of PU.1. Our data
      demonstrate that GFI-1 physically interacts with PU.1, repressing PU.1-dependent
      transcription. This repression is functionally significant, as GFI-1 blocked PU.1
      induced macrophage differentiation of a multipotential hematopoietic progenitor
      cell line. Retroviral expression of GFI-1 in primary murine hematopoietic
      progenitors increased granulocyte differentiation at the expense of macrophage
      differentiation. We interbred Gfi-1(+/-) and PU.1(+/-) mice and observed that
      heterozygosity at the PU.1 locus partially rescued the Gfi-1(-/-) mixed myeloid
      lineage phenotype, but failed to restore granulocyte differentiation. Our data
      demonstrate that GFI-1 represses PU.1 activity and that lack of this repression
      in Gfi-1(-/-) myeloid cells contributes to the observed mixed lineage phenotype.

PMID- 17197706
TI  - Clinical outcomes following percutaneous coronary intervention with drug-eluting
      vs. bare-metal stents in dialysis patients.
AB  - BACKGROUND: Late mortality among dialysis patients undergoing PCI with bare-metal
      stents is high. The impact of drug-eluting stent use on outcomes in such patients
      is unclear. OBJECTIVE: To compare the clinical outcomes of dialysis patients
      undergoing coronary stenting with versus without the use of drug-eluting stents.
      METHODS: Baseline features and outcomes were compared in dialysis patients
      undergoing coronary stent implantation using either bare-metal devices only (n =
      41) or drug-eluting stents (n = 33), in recruitment waves 3 (2001-2002; n =
      2,047) and 4 (2004; n = 2,112) of the National Heart Lung, and Blood Institute
      Dynamic Registry. The primary study endpoint was the composite of major adverse
      cardiac events (MACE), defined as death, myocardial infarction (MI) or any repeat
      revascularization procedure at 1-year follow up. RESULTS: Baseline and procedural
      features and in-hospital MACE rates were similar in both groups. Cumulative 1
      year rates of the composite MACE endpoint and all-cause mortality were lower in
      patients treated with drug-eluting versus bare-metal stents (25.2% vs. 57.3%; p =
      0.01, and 18.4% and 36.8%, respectively; p = 0.09). By multivariable analysis,
      drug-eluting versus bare-metal stent use was independently associated with
      freedom from the composite MACE endpoint (hazard ratio = 0.24, 95% CI [0.10
      0.60]; p = 0.002) and with a trend to lower all-cause mortality (HR = 0.40 [0.15
      1.05]; p = 0.06) at 1 year. CONCLUSION: In this cohort of dialysis patients
      undergoing percutaneous coronary intervention (PCI), drug-eluting versus bare
      metal stent implantation was associated with enhanced freedom from 1-year MACE.
      Given previous bare-metal stent data indicating worse outcomes after PCI than
      after bypass surgery in dialysis patients, randomized trials comparing these
      strategies in the drug-eluting stent era are needed.

PMID- 17197707
TI  - Severe, diffuse coronary artery spasm after drug-eluting stent placement.
AB  - OBJECTIVES: Three cases of severe, diffuse coronary artery spasm after drug
      eluting stent placement at our institution prompted this review. BACKGROUND: Drug
      eluting stents have gained widespread use due to extraordinarily low rates of
      restenosis. Despite these generally superior clinical outcomes, the specter of
      rare idiosyncratic reactions remains a concern. METHODS: We performed searches of
      Medline and the U.S. FDA Manufacturer And User facility Device Experience
      database (MAUDE) to identify and describe spasm after coronary stent placement.
      Searches included drug-eluting and bare-metal stents. Institutional cases are
      reviewed. Location, time course and outcome of cases are described. RESULTS:
      Thirteen cases of spasm were identified after stent placement. Seven cases
      occurred after Cypher drug-eluting stent placement, 2 after Taxus drug-eluting
      stent placement, 1 after BiodivYsio and 3 after bare-metal stents. Five patients
      experienced diffuse, multivessel spasm--2 after Cypher, 2 after Taxus, and 1
      after a Velocity stent. Of these 5 patients, 2 died. An additional 2 required
      intra-aortic balloon pump placement for cardiogenic shock. Another had persistent
      symptomatic, diffuse coronary spasm documented by angiography at 1 year.
      CONCLUSIONS: We describe coronary spasm after stent placement, particularly after
      drug-eluting stents. Outcomes associated with diffuse severe spasm after stenting
      are poor, and the pathophysiology remains poorly understood.

PMID- 17197708
TI  - Vasoconstriction and coronary artery spasm after drug-eluting stent placement.

PMID- 17197709
TI  - Troponin-positive chest pain with unobstructed coronary arteries: a role for
      delayed enhanced cardiovascular magnetic resonance in the diagnosis of non-ST
      elevation myocardial infarction.

PMID- 17197710
TI  - Incidence and prognosis of pacemaker lead-associated masses: a study of 1,569
      transesophageal echocardiograms.
AB  - Endovascular lead infection is an uncommon but serious problem. Transesophageal
      echocardiography (TEE) is a useful tool for identification of pacemaker lead
      vegetations. Additionally, incidental echogenic masses are occasionally
      identified by TEE. The prognosis and optimal treatment of either suspected lead
      infection or an incidental mass is poorly understood. OBJECTIVE: The purpose of
      this study was to examine the incidence and clinical course of pacemaker lead
      masses. METHODS: A total of 1,569 sequential TEE examinations performed from
      January 2002 to January 2005 were reviewed. Retrospective chart analysis of
      patients with a pacing lead-associated mass was performed to review the
      indication for TEE as well as clinical management. Telephone follow up was also
      performed. RESULTS: During 125 TEE examinations, pacemaker leads were visualized
      in the right-sided chambers. Fifteen studies demonstrated an echogenic mass
      associated with the lead. In 9 of these studies, endocarditis was suspected, and
      the mass was felt to be a vegetation: 6 were treated with antibiotics alone, with
      1 death attributed to a complication of endocarditis (autopsy proven massive
      pulmonary embolus); 3 patients were treated with lead extraction, both were alive
      at follow up; 1 patient was lost to follow up after the TEE. Six patients (5%)
      were found incidentally to have a mass on the pacing lead during TEE: 3 were
      treated with warfarin; 2 received no specific therapy; and 1 underwent surgical
      debridement of the lead during valve surgery. All of the patients in this group
      were alive at follow up, and no significant clinical events attributable to the
      lead-associated mass were observed. CONCLUSIONS: TEE identified an echogenic mass
      on 12% of the leads imaged, with 60% having suspected endocarditis. The mortality
      rate of lead vegetation was 11%. An incidental mass was noted on 5% of the leads,
      with no significant associated morbidity or mortality observed.

PMID- 17197711
TI  - Bugs and clots: the value of transesophageal echocardiography in defining
      permanent pacemaker lead infections.

PMID- 17197712
TI  - PCI with and without abciximab after upstream eptifibatide use: outcomes in high
      risk patients.
AB  - BACKGROUND: Abciximab is often used to treat high-risk patients during
      percutaneous coronary intervention (PCI). Recent data indicate, however, that
      upstream and postprocedural treatment with low-dose glycoprotein (GP) IIb/IIIa
      inhibitors may be more beneficial than abciximab during and after PCI. Whether
      abciximab can be used safely or effectively during PCI for high-risk patients
      after upstream treatment with eptifibatide in patients with acute coronary
      syndromes (ACS) is not known. METHODS: Clinical outcomes were evaluated in 289
      patients with ACS who had upstream treatment with eptifibatide, and abciximab
      (EA) during PCI, and compared to 560 ACS patients who had both upstream and
      interventional treatment with eptifibatide (EE). RESULTS: Bleeding and vascular
      complications of the two groups were similar. Overall, 1-year major adverse
      cardiac event (MACE) rates were similar: 26.0% in the EA group and 25.2% in the
      EE group; p = 0.82. In patients with unstable angina, the hazard of MACE at 1
      year was higher with EA than EE, 1.98 (1.23-3.18), due to significantly higher
      rates of repeat revascularization in the EA group. In patients with myocardial
      infarction (MI), the hazard of MI or death at 1 year was lower in the EA than the
      EE group, 0.50 (0.27-0.93). CONCLUSION: In this single-center observational
      study, the use of abciximab for PCI after upstream use of eptifibatide for ACS
      was safe. Abciximab was of no benefit in patients with unstable angina, but was
      associated with lower MI or death in patients with MI. These observations are
      consistent with recent findings indicating that abciximab is of benefit in
      patients with NSTEMI, but not lower-risk patients.

PMID- 17197713
TI  - Successful mobilization of peripheral blood stem cells by use of granulocyte
      colony stimulating factor and their transcoronary transplantation in a patient
      after cardiogenic shock due to acute myocardial infarction.

PMID- 17197715
TI  - Percutaneous thrombectomy for pulmonary embolism.
AB  - The current treatment of massive pulmonary embolism (PE) has been either
      thrombolysis or surgical embolectomy. Percutaneous rheolytic thrombectomy,
      however, has emerged as an alternative treatment in patients with
      contraindications to thrombolysis. This case illustrates the usefulness of the
      AngioJet(R) thrombectomy catheter in patients with contraindications to
      thrombolytics. Three-dimensional computed tomography imaging demonstrated the
      effectiveness of treatment in this patient with massive PE.

PMID- 17197714
TI  - Strategies for optimizing outcomes in the NSTE-ACS patient The CATH (cardiac
      catheterization and antithrombotic therapy in the hospital) Clinical Consensus
      Panel Report.
AB  - This paper provides a comprehensive up-to-date review of the medical and invasive
      management of patients with non- ST-segment elevation acute coronary syndromes
      (NSTE-ACS). The authors have summarized findings from key clinical trials
      published recent years that contribute to clinicians' understanding of how best
      to optimize therapy. The goals for the management of NSTE-ACS are rapid and
      accurate risk stratification, appropriate and institution-specific triage to
      interventional versus medical strategies and optimal pharmacologic therapy--all
      of which provide for a smooth and seamless transition of care between the
      emergency department and the cardiology service. High-risk features or absolute
      treatment trigger criteria that support more aggressive medical therapy (i.e.,
      addition of small-molecule GP IIb/IIIa inhibitor to a core regimen of aspirin,
      enoxaparin, and in most cases, clopidogrel) and/or that would direct clinicians
      toward percutaneous, mechanical/interventional strategies as the preferred
      modality include, but are not limited to, the presence of one or more of the
      following: (1) elevated cardiac markers (troponin and/or CK-MB); (2) elevated
      levels of inflammatory markers (particularly CRP > 3 microg/dl); (3) age > 65
      years; (4) presence of ST-T wave changes; (5) TIMI Risk Score greater than or
      equal to 4; (6) diabetes; and/or (7) clinical instability in the setting of
      suspected NSTE-ACS. Specific clinical, ECG and/or biochemical trigger points
      modulate the aggressiveness of both the medical therapy and the propensity to
      perform early angiography with or without subsequent revascularization in
      patients with NSTE-ACS. Although additional refinements and changes in ACS
      management are still to come, evidence-based strategies suggest that prompt
      mechanical revascularization is associated with the best possible clinical
      outcomes, particularly for patients with high-risk features and in whom benefits
      of adjunctive, pharmacoinvasive antithrombotic therapies can be consolidated.
      Patient transfer for cardiac catheterization/percutaneous coronary intervention
      (PCI) is strongly recommended in patients who manifest high-risk features and/or
      aggressive treatment trigger criteria, so that this high-risk subgroup may
      receive definitive, interventional and/or cardiology-directed specialty care at
      appropriate sites of care. When available, interventional management is preferred
      in these patients. The importance of safe and effective anticoagulation in the
      spectrum of management strategies has been confirmed, and the evidence in support
      of enoxaparin and other antithrombotic agents has been reviewed. Dosing
      recommendations for enoxaparin use in the setting of PCI have been issued by the
      CATH Panel and have been summarized in this consensus report. Similar
      recommendations have been presented for the use of oral antiplatelet agents and
      GP IIb/IIIa antagonists. The addition of statins, ACE-inhibitors and beta
      blockers is also stressed as part of a comprehensive secondary cardioprotective
      strategy for patients with coronary heart disease.

PMID- 17197716
TI  - Large spontaneous coronary artery-to-right ventricular fistula.
AB  - We report a case of the spontaneous formation of a left anterior descending
      artery to right ventricular fistula. The unprovoked appearance of this fistulous
      connection was clearly documented by serial angiography and confirmed during
      surgery.

PMID- 17197717
TI  - To close or not to close: PFO, sex and cerebrovascular events.
AB  - We report on 2 patients with cerebrovascular events associated with sexual
      activity and PFO who subsequently underwent endovascular patent foramen ovale
      (PFO) closure. The concurrence of sexual activity (a Valsalva equivalent) at
      symptom onset, together with supporting data, prior paradoxical embolus in 1
      case, elevated D-dimer in another, supported paradoxical embolization as the most
      likely mechanism of the cerebrovascular events. These cases emphasize that
      clinicians evaluating patients for PFO closure should explicitly inquire about
      sexual activity at stroke onset.

PMID- 17197718
TI  - Late stent thrombosis mimicking focal restenosis after sirolimus stent
      implantation: angiographic and intravascular ultrasound appraisal.

PMID- 17197719
TI  - Ostial RCA intervention: guiding catheter challenges and use of a buddy wire to
      perform focused-force angioplasty on a severely calcific ostial right coronary
      lesion.
AB  - Ostial coronary disease presents a challenge from multiple perspectives with
      regard to percutaneous intervention. We present a novel case of a technically
      challenging ostial right coronary artery calcified lesion with a bar of calcium
      at the aorto-ostial junction which prevented intubation with multiple guiding
      catheters. We describe the use of a buddy wire as a technique for focused-force
      angioplasty with slow incremental balloon inflation of increasing diameter for
      plaque modification prior to stenting in a situation where rotational atherectomy
      and cutting balloon angioplasty were not an option.

PMID- 17197721
TI  - Fibrinolysis and coronary stenting for treatment of an acute inferior myocardial
      infarction after ascending aortic aneurysm repair with conduit coronary grafts.

PMID- 17197720
TI  - Percutaneous treatment of a large coronary aneurysm with a ball thrombus: an
      interventional challenge.

PMID- 17197722
TI  - Retrograde-antegrade left main coronary artery stenting.

PMID- 17197723
TI  - Atomic force microscopy and FT-IR spectroscopy investigations of human heart
      valves.
AB  - Human aortic, mitral, tricuspid and pulmonary heart valves were investigated by
      the contact mode atomic force microscopy (AFM) in air, and using FT-IR
      spectroscopy in the frequency range 950-4000 cm(-1). Heart valves were collected
      post mortem from 65-78 years old patients who died from non-cardiac diseases. All
      of the examined valves showed considerable heterogeneity in the surface
      topography of collagen fibrils as well as in their organization on the tissue
      surface. The AFM images revealed areas with significantly different spatial
      organization of the collagen fibril bundles. We observed zones with
      multidirectional, stacked collagen fibrils as well as areas of thin fibrils
      packed regularly, densely and "in phase". The majority of the collagen fibrils
      reproduced the typical transverse D-banding pattern, with the band interval
      varying in rather wide range of 70-90 nm. Using AFM imaging, objects that
      correspond to some pathological states of heart valves at their early stages,
      i.e. some forms of mineral deposits, were observed. The FT-IR spectra allowed us
      to recognize main components, i.e. collagen and elastin, in di.erent layers
      (ventricularis, fibrosa) of the valve leaflets as well as they gave also support
      for the presence of mineral deposits on the valve surface. The presented results
      showed, that the AFM imaging and FT-IR spectroscopy can be applied as a
      complementary methods for structural characterization of heart valves at the
      molecular and supramolecular levels.

PMID- 17197724
TI  - Oxidation pattern of the anticancer drug ellipticine by hepatic microsomes -
      similarity between human and rat systems.
AB  - Ellipticine is an antineoplastic agent, whose mode of action is based mainly on
      DNA intercalation, inhibition of topoisomerase II and formation of DNA adducts
      mediated by cytochrome P450 (CYP). We investigated the ability of CYP enzymes in
      rat, rabbit and human hepatic microsomes to oxidize ellipticine and evaluated
      suitable animal models mimicking its oxidation in humans. Ellipticine is oxidized
      by microsomes of all species to 7-hydroxy-, 9-hydroxy-, 12-hydroxy-, 13
      hydroxyellipticine and ellipticine N(2)-oxide. However, only rat microsomes
      generated the pattern of ellipticine metabolites reproducing that formed by human
      microsomes. While rabbit microsomes favored the production of ellipticine N(2)
      oxide, human and rat microsomes predominantly formed 13-hydroxyellipticine. The
      species difference in expression and catalytic activities of individual CYPs in
      livers are the cause of these metabolic differences. Formation of 7-hydroxy- and
      9-hydroxyellipticine was attributable to CYP1A in microsomes of all species.
      However, production of 13-hydroxy-, 12-hydroxyellipticine and ellipticine N(2)
      oxide, the metabolites generating DNA adducts, was attributable to the
      orthologous CYPs only in rats and humans. CYP3A predominantly generates these
      metabolites in rat and human microsomes, while CYP2C3 activity prevails in
      microsomes of rabbits. The results underline the suitability of rat species as a
      model to evaluate human susceptibility to ellipticine.

PMID- 17197725
TI  - Oxaliplatin, an anticancer agent that affects both Na+ and K+ channels in frog
      peripheral myelinated axons.
AB  - The use of oxaliplatin, a relatively new chemotherapeutic agent, is somewhat
      limited since it produces a specific peripheral neuropathy regarding other
      neurotoxic anticancer platinum analogues. In order to investigate the mechanism
      of such a peripheral neuropathy, the effects of 1-100 micromol/l oxaliplatin were
      assessed on the nodal ionic currents of single frog myelinated axons as a model
      of peripheral excitable membranes. Oxaliplatin decreased both Na(+) and K(+)
      currents in a dose-dependent manner and within 5-10 min, without producing any
      marked changes in the current kinetics. It was about three to eight times more
      effective in reducing the Na(+) than the K(+) current. In addition, it shifted
      the voltage-dependence of both Na(+) and K(+) conductances towards negative
      membrane potentials. A negative shift in the steady-state inactivation-voltage
      curve of the peak Na(+) current was also observed in the presence of oxaliplatin.
      These effects were not reversed by washing the myelinated axons with an
      oxaliplatin-free solution for at least 30 min. It is concluded that oxaliplatin
      modifies the voltage-dependent ionic channels mainly by altering the external
      surface membrane potential. The knowledge of such a mechanism may help to
      counteract the neurotoxic action of this anticancer agent.

PMID- 17197726
TI  - Effects of N-acyl-2-hydroxymethyl aziridines on in vitro proliferative responses
      of human lymphocytes stimulated by mitogens.
AB  - Aziridines have been shown to possess marked immunotropic activity. The aim of
      this work was to study the in vitro effects of different concentrations of three
      novel aziridines, 2-hydroxy-methyl-1-(N-phtaloylglycyl) aziridine (aziridine 1),
      2-hydroxy-methyl-1-(N-phtaloylalanyl) aziridine (aziridine 2) and 2-hydroxy
      methyl-1-(N-phtaloylphenylalanyl) aziridine (aziridine 3), on the proliferative
      responses of human lymphocytes stimulated by mitogens (concanavalin A (Con A) and
      lipopolysaccharide (LPS)), and interleukin-2 (IL-2), interleukin-6 (IL-6)
      secretion. The results showed that aziridines 1 and 3 significantly stimulated
      the resting and Con A or LPS lymphocyte proliferation at concentrations between 1
      micromol/l and 1 mmol/l, in a dose-dependent manner, the action of aziridine 3
      being the highest. They also increased IL-2 and IL-6 secretion. However,
      aziridine 2 had no effect on the resting lymphocyte proliferation in the absence
      of mitogens, at any concentration used, reduced Con A-stimulated T lymphocyte
      proliferation and LPS- stimulated B lymphocyte proliferation in a dose dependent
      manner and diminished IL-2 and IL-6 production. None of the three aziridines
      affected cell viability. In conclusion, the three aziridines used in this study
      displayed immunomodulatory properties. Aziridines 1 and 3 are potentially
      immunostimulant while aziridine 2 is immunosuppressive and could be used to
      provide nonspecific cell-mediated immune responses.

PMID- 17197728
TI  - H/D isotope effects on protein hydration and interaction in solution.
AB  - An approach has been suggested to study the H/D isotope effect on protein-water
      and protein-protein intermolecular interactions by determining the content of non
      freezing water using low-temperature (1)H NMR in mixed (H2O/D2O) water solutions.
      Direct data are obtained on the amount of H2O adsorbed (absolute hydration) in
      presence of the heavy isotope (deuterium D), and isothermals of H2O/D2O
      fractionation at protein surface groups are presented for temperatures between 
      10 degrees C and -35 degrees C and solutions of varying composition. The
      fractionation factor, phi = [x/(1 - x)]/[x(0)/(1 - x(0))], where x and x(0) are
      the fractions of deuterons in hydration and bulk water, respectively, appeared to
      be extremely high: phi >> 1 at 0.03 < x(0) < 0.10. The high values of phi
      indicate a decrease in apparent hydration of protein molecules. A probable reason
      of the effect can be an inter-protein molecular solvent-mediated interaction
      induced by D2O. The excess of phi over 1 appears to provide a quantitative
      estimate of the fraction of hydration water affected by such interaction.

PMID- 17197727
TI  - Changes in the function and ultrastructure of vessels in the rat model of
      multiple low dose streptozotocin-induced diabetes.
AB  - In this study we investigated functional changes in the femoral artery and
      ultrastructural alterations in mesenteric vessels and capillaries in the rat
      model of multiple low dose streptozotocin (STZ)-induced diabetes. Participation
      of oxidative stress in this model of diabetes was established by studying the
      effect of the pyridoindole antioxidant stobadine (STB) on diabetes-induced
      impairment. Experimental diabetes was induced by i.v. bolus of STZ (20 mg/kg)
      given for three consecutive days to male rats. At the 12(th) week following STZ
      administration, the animals revealed typical signs of diabetes, such as
      polyphagia, polydypsia and polyuria. There was no weight gain in the diabetic
      groups throughout the experiment. No exitus occurred in any group. Diabetes was
      characterised with high levels of plasma glucose, no significant changes in lipid
      metabolism, decreased serum levels of glutathione, increased serum levels of the
      lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAGA), injured endothelial
      relaxant capacity of the femoral artery and alterations in ultrastructure of
      mesenteric arteries and capillaries. Antioxidant STB in the dose of 25 mg/kg body
      weight i.p. (5 times per week) did not influence glucose levels, however, it
      mitigated biochemical, functional and ultrastructural changes induced by
      diabetes, suggesting a role of reactive oxygen species in diabetes-induced tissue
      damage.

PMID- 17197729
TI  - Influence of membrane phospholipid composition and structural organization on
      spontaneous lipid transfer between membranes.
AB  - Investigations were carried out on the influence of phospholipid composition of
      model membranes on the processes of spontaneous lipid transfer between membranes.
      Acceptor vesicles were prepared from phospholipids extracted from plasma
      membranes of control and ras-transformed fibroblasts. Acceptor model membranes
      with manipulated levels of phosphatidylethanolamine (PE), sphingomyelin and
      phosphatidic acid were also used in the studies. Donor vesicles were prepared of
      phosphatidylcholine (PC) and contained two fluorescent lipid analogues, NBD-PC
      and N-Rh-PE, at a self-quenching concentration. Lipid transfer rate was assessed
      by measuring the increase of fluorescence in acceptor membranes due to transfer
      of fluorescent lipid analogues from quenched donor to unquenched acceptor
      vesicles. The results showed that spontaneous NBD-PC transfer increased upon
      fluidization of acceptor vesicles. In addition, elevation of PE concentration in
      model membranes was also accompanied by an increase of lipid transfer to all
      series of acceptor vesicles. The results are discussed with respect to the role
      of lipid composition and structural order of cellular plasma membranes in the
      processes of spontaneous lipid exchange between membrane bilayers.

PMID- 17197730
TI  - Tetraphenylphosphonium-selective electrode as a tool for evaluating mitochondrial
      permeability transition pore function in isolated rat hepatocytes.
AB  - The changes in mitochondrial membrane potential (Deltapsi(m)) were used as an
      indicator for evaluating the mitochondrial permeability transition pore (MPTP)
      function. We found that in situ mitochondria in digitonin-permeabilized
      hepatocytes were coupled and responded to the addition of substrates, inhibitors
      and uncouplers. Ca(2+)-induced Deltapsi(m) dissipation was caused by MPTP opening
      because this process was inhibited by cyclosporin A. MPTP opening was enhanced by
      the pro-oxidant tert-butyl hydroperoxide.

PMID- 17197732
TI  - The external laryngeal nerve in thyroid surgery: the 'no more neglected' nerve.
AB  - AIMS: To describe a novel surgical technique of 'lateralization' of superior pole
      to identify and save external branch of superior laryngeal nerve (EBSLN) during
      thyroidectomy. SETTINGS AND DESIGN: Prospective, nonrandomized at a tertiary care
      hospital in a specialized unit. MATERIAL AND METHODS: Over 30 months, 46 patients
      underwent thyroidectomy using technique of 1) 'Lateralization' of upper pole and
      dissection of avascular cricothyroid space 2) identification of EBSLN 3)
      skeletonization and individual ligation of superior thyroid vessels. Identified
      nerves were classified according to Cernea's classification. Outcomes were number
      of nerves identified, number of 'at risk' nerves' bilateral asymmetry and
      incidence of injury assessed by subjective interview and indirect laryngoscopy.
      RESULTS: Of the 78 dissected superior poles, nerves could be identified in 72
      (92.31%). There were 22 (28.2%) type I, 42 (53.54%) IIa and 8 (10.25%) IIb 'at
      risk' nerves. In 32 patients with bilateral dissections, asymmetry of nerve was
      noted in 15%. Injury to nerve was not recorded in any of the patients. Average
      weight of glands was 69.59 g. Thyroidectomy was performed for benign disease in
      28, malignancy in 4 and thyrotoxicosis in 14 patients. CONCLUSIONS: With
      technique of 'lateralization' and 'skeletonization and individual ligation of the
      superior vessels,' EBSLN identification increases and injury can be prevented.
      These results relate to the utilization of specific surgical technique and it is
      reasonable to expect that most surgeons, once familiar with the technique, should
      be able to achieve similar outcomes.

PMID- 17197731
TI  - Ghrelin suppression of potassium currents in smooth muscle cells of human
      mesenteric artery.
AB  - Ghrelin is a 28-amino acid peptide hormone which modulates many physiological
      functions including cardiovascular homeostasis. Here we report some novel
      findings about the action of ghrelin on smooth muscle cells (SMC) freshly
      isolated from human mesenteric arteries. Ghrelin (10(-7) mol/l) significantly
      suppressed the iberiotoxin-blockable component of potassium currents (I(K)) and
      depolarized the cell membrane, while having no effect on Ca(2+) currents.
      Inhibition of inositol-trisphosphate (IP(3))-activated Ca(2+) release channels,
      depletion of sarcoplasmic reticulum (SR) Ca(2+) stores, blockade of phospholipase
      D (PLD) or protein kinase C (PKC) each abolished the effect of ghrelin on I(K),
      while the inhibition of phospholipase C (PLC) did not. These data imply that in
      human mesenteric artery SMC ghrelin suppresses I(K) via PLD, PKC and SR Ca(2+)
      dependent signaling pathway.

PMID- 17197733
TI  - Status of lipid peroxidation, glutathione, ascorbic acid, vitamin E and
      antioxidant enzymes in patients with osteoarthritis.
AB  - BACKGROUND: The exact pro-oxidant and antioxidant status in osteoarthritis
      patients is still not clear. To add a new insight to the question, changes in the
      erythrocyte lipid peroxidation products (MDA), levels of glutathione (GSH),
      ascorbic acid and plasma vitamin E (nonenzymatic antioxidant parameters); and
      activities of antioxidant enzymes superoxide dismutase (SOD), glutathione
      peroxidase (GPX), catalase in erythrocytes and plasma glutathione - S -
      transferase (GST) were measured in patients with osteoarthritis. AIM: This work
      was undertaken to assess oxidative stress and antioxidant status in patients with
      osteoarthritis. SETTINGS AND DESIGN: The study was conducted in 20 patients and
      compared to controls. Levels of erythrocyte MDA, GSH, ascorbic acid, plasma
      vitamin E; and activities of antioxidant enzymes were measured in patients with
      osteoarthritis. MATERIALS AND METHODS: Erythrocyte GSH was measured by the method
      of Beutler et al. Ascorbic acid levels were measured by the method of Tietz.
      Plasma vitamin E levels were measured by the method of Baker et al. MDA was
      determined as the measure of thio barbituric acid reactive substances (TBARS).
      SOD activity in the hemolysate was measured by the method of Misra and Fridovich.
      Activity of catalase was measured by the method of Beers and Sizer. GPX activity
      was measured as described by Paglia and Valentine in erythrocytes and Plasma GST
      activity was measured as described by Warholm et al. These parameters were
      measured in 20 patients and compared to controls. STATISTICAL ANALYSIS:
      Statistical analysis between group 1 (controls) and group 2 (patients) was
      performed by the student's t - test using the stat -view package. RESULTS: It was
      observed that there was a significant increase in erythrocyte MDA levels; SOD,
      GPX and plasma GST activities; and a significant decrease in erythrocyte GSH,
      ascorbic acid, plasma vitamin E levels and catalase activity in patients with
      osteoarthritis when compared to controls. CONCLUSIONS: The results of our study
      suggest higher oxygen-free radical production, evidenced by increased MDA and
      decreased GSH, ascorbic acid, vitamin E and catalase activity, support to the
      oxidative stress in osteoarthritis. The increased activities of antioxidant
      enzymes may be a compensatory regulation in response to increased oxidative
      stress.

PMID- 17197735
TI  - Unruptured postdated pregnancy with a live fetus in a noncommunicating
      rudimentary horn.
AB  - Pregnancy in a noncommunicating rudimentary horn is an extremely rare and a life
      threatening condition as it mostly terminates by rupture by the second trimester
      of pregnancy. Postdated pregnancy and delivery of a live fetus in a rudimentary
      horn have been rarely reported. A case of noncommunicating unruptured rudimentary
      horn pregnancy progressing to 41 weeks and 3 days period of gestation where the
      diagnosis was initially missed at obstetric sonogram at 18 and 34 weeks and then
      misdiagnosed later as abdominal pregnancy is being reported. Preoperative
      diagnosis, successful delivery of a live fetus and excision of the rudimentary
      horn was performed.

PMID- 17197734
TI  - Pediatric cataract and surgery outcomes in Central India: a hospital based study.
AB  - BACKGROUND: A review of pediatric cataract cases operated between January 2003
      and March 2005 in the tribal belt of central India was carried out. AIM: We
      present the profile of cataract cases in children <or=18 years and postoperative
      visual status in the eyes operated upon. SETTINGS AND DESIGN: This was a
      retrospective medical record retrieval type of cohort study in a hospital
      setting. MATERIALS AND METHODS: Pediatric ophthalmologists examined children and
      operated eyes with cataract. The personal profile, preoperative, intraoperative
      and postoperative details were noted. The surgical procedures included cataract
      extraction, intraocular lens implantation, posterior capsulorrhaxis and anterior
      vitrectomy in most of the cases. We evaluated the visual status of eyes with
      cataract before and 6 weeks after surgery. STATISTICAL ANALYSIS: We used
      univariate type of parametric type of statistical analysis. RESULTS: A total of
      575 eyes of 502 children had cataract. Cataract in 65 children was bilateral and
      in 437 cases it was unilateral. Congenital cataracts were in 88 (17.5%) eyes.
      Traumatic cataracts were noted in 170 (33.9%) eyes. The proportion of cataract
      was higher in males than in females. Variation in 'number of cataracts' among
      different age groups was noted. Vision following surgery was more than 6/18 in 84
      (16.4%) eyes. The vision could not be assessed in 256 (44%) eyes. CONCLUSION:
      Improvement of child health care is needed for early detection of cataract in
      children. Role of rubella and trauma in childhood cataract should be investigated
      and addressed. Visual assessment and postoperative care should be further
      improved.

PMID- 17197736
TI  - Rudimentary horn pregnancy: prerupture diagnosis and management.
AB  - A unicornuate uterus with a rudimentary horn is a rare mullerian abnormality
      which may cause many gynecological and obstetrical complications. Rupture of
      pregnant rudimentary horn in the second trimester is the usual presentation,
      resulting in maternal morbidity and even mortality.

PMID- 17197737
TI  - Dolichoectasia of vertebrobasilar system: a rare cause of tic douloureux.

PMID- 17197738
TI  - Indian medical graduates in the UK: end of the road for postgraduate training?

PMID- 17197739
TI  - Cervical cancer screening in India: strategies revisited.
AB  - With the change in the life styles and demographic profiles of developing
      countries, noncommunicable diseases are emerging to be important health problems
      that demand appropriate control program before they assume epidemic proportion.
      One of these is the problem of cancer. In India, cervical cancer is a significant
      problem in terms of incidence, mortality and morbidity. Cervical cancer is a
      disease that can be prevented through both primary prevention and early detection
      using screening techniques. Several screening modalities are now available for
      early detection of cervical cancer and its precursor lesions. They all differ
      with regard to their test characteristics, feasibility and economic
      considerations. This communication reviews different aspects of these screening
      modalities and provides different options considering mass application.

PMID- 17197740
TI  - [Adjuvant chemotherapy for non-small cell lung cancer].
AB  - Recently, several randomized trials with a large number of enrolled patients have
      shown that postoperative adjuvant treatment improves survival among patients with
      completely resected non-small cell lung cancer (NSCLC). Platinum-based
      chemotherapy has been reported to be effective for patients with postoperative
      stage I to IIIA NSCLC in western countries. On the other hand, uracil-tegafur was
      also shown to improve survival among patients with stage I adenocarcinoma in
      Japan. We reviewed the results of recent randomized trials and meta-analyses, and
      discuss the current role and problems related to adjuvant chemotherapy in NSCLC.

PMID- 17197741
TI  - [Prognostic factors of vulvar cancer].
AB  - While vulvar cancer is rare in Japan, the management of this disease has changed
      dramatically over the past 20 years. The radical vulvectomy that was previously
      believed to be the only effective treatment for vulvar cancer has now been
      replaced by more individualized treatments, from the standpoint of QOL. Because
      the lesion diameter and groin node status (laterality and number positive) are
      the most important prognostic factors of vulvar cancer, numerous refinements have
      been made in the management. The refinements include conservative surgery for
      patients with isolated lesions, omission of groin lymph node dissection in T 1 A
      tumors with stromal invasion <1 mm, and omission of contralateral groin lymph
      node dissection in T 1 tumor with negative ipsilateral node metastasis. In
      addition to these changes, elimination of groin dissection using sentinel lymph
      node procedure and preoperative chemoradiation for patients with advanced disease
      are currently under investigation. In this review, we discuss these issues along
      with the evidence upon which these therapies are based.

PMID- 17197742
TI  - [Prognostic factors of vaginal cancer].
AB  - Vaginal cancer is a rare disease entity in the gynecologic oncology field.
      Prognostic factors of the disease, however, are not established to date. Possible
      prognostic factors such as tumor location in vagina, tumor size, age,staging and
      histopathological grading are discussed following a literature review. Because
      the case number of the report from a single institute is really limited,
      accumulation and analysis of the case of multi-institutional registration are
      mandatory.

PMID- 17197744
TI  - [Prognostic factors uterine corpus cancer].
AB  - The accumulated clinico-pathological dates and recent molecular biological
      studies have identified several prognostic factors for endometrial cancers. FIGO
      staging has taken into consideration of the tumor expansion and is the most
      important predictor in evaluating patient outcome. Characteristics of tumor
      biology, such as morphology of tumor and depth of invasion are also important
      prognostic considerations. Molecular markers indicating genetic/molecular events
      in cancer biology appear to be the 3rd predictors in estimating the prognosis.
      Finally, treatment of uterine corpus cancer can be directly related to prognosis.
      Postoperative chemotherapy is gradually taking precedence over irradiation in
      considering evidence-based medicine.

PMID- 17197743
TI  - [Prognostic factors of uterine cervical cancer].
AB  - The large majority of gynecologic malignancies are comprised of uterine cervical
      cancer, endometrial cancer and ovarian cancer. Prognostic factors for each
      disease are based on various clinical pathological features, including clinical
      stage, tumor size, and lymph node metastatis for uterine cervical cancer. In
      addition to these factors, recent studies have investigated the role of various
      molecules including tumor markers and Hb level, apoptosis-related molecules as
      well as various genetic abnormalities as prognostic factor or indicators for
      uterine cervical cancer. This molecular background of uterine cervical cancer
      will shape future directions in the increasingly individualized basis of
      treatment.

PMID- 17197745
TI  - [Prognostic factors of ovarian cancer].
AB  - Prognostic factors of ovarian cancer were reviewed. These factors may be divided
      into three categories: patient factors, tumor factors and treatment factors.
      Among factors related to patients, age and performance status significantly
      influenced the survival rate. Tumor factors such as stage, histopathology,
      histological grade and expression of cancer-related genes showed significant
      impact on survival as well. Treatment factors such as residual tumor size,
      chemotherapeutic regimens are also important for the prognosis. According to
      these prognostic factors and therapeutic results, maximal surgical efforts for
      the debulking surgery along with paclitaxel and carboplatin chemotherapy are
      recommended especially for patients with advanced disease.

PMID- 17197746
TI  - [A phase I/II study of docetaxel/TS-1 with radiation for esophageal cancer
      patients--step 1].
AB  - The therapy 5-FU and CDDP with radiation is thought to be the standard therapy
      for esophageal cancer patients by now. However, the therapy is associated with a
      comparatively high incidence of gastrointestinal disorders and requires
      hospitalization. We have proposed a new regimen of Docetaxel and TS-1 with
      radiation for maintaining of QOL and improving outcome. Step 1 of the clinical
      phase I/ II study was conducted for 10 cases from May 2004 to March 2006.
      Treatment could be accomplished in all cases, and no treatment-related deaths or
      adverse events of grade 4 were observed in any case. As for hematotoxicity, one
      case had leucopenia of grade 3 and neutropenia of grade 2. As for non-hematotoxic
      adverse events, anorexia of grade 3 was recognized in one case of level 3. The
      response rate evaluated by RECIST was 66% (CR in 2 cases, PR in 4 cases), and the
      rate based on the Guide Lines for the Clinical and Pathologic Studies on
      Carcinoma of Esophagus by the Japanese Society for Esophageal Cancer was 70% (CR
      in 3 cases, PR in 4 cases). We assumed that the recommended dosage of TXT was 30
      mg/m(2) and that of TS-1 was 60 mg/m(2) with radiotherapy of 60 Gy. This
      combination therapy may be recommended because of fewer adverse events and a
      higher responsive rate than the standard therapies. We intend to continue this
      study to step 2 and 3, and to reveal the response rate and adverse events for
      more esophageal cancer patients.

PMID- 17197747
TI  - [A phase I study of intraperitoneal plus intravenous paclitaxel against gastric
      cancer with peritoneal dissemination (HGCG 0301)].
AB  - The safety of the intraperitoneal (ip) plus intravenous (iv) paclitaxel against
      gastric cancer with peritoneal dissemination was evaluated on a phase I dose
      escalation trial. Patients were treated with ip paclitaxel administered in 500 ml
      of normal saline before closing the abdomen, using the following dose levels:
      level 1, 50 mg/m(2); level 2, 60 mg/m(2); level 3, 70 mg/m(2); and level 4, 80
      mg/m(2), followed by iv infusion of the same doses of paclitaxel on days 14 and
      21. Twelve patients were enrolled in this study: 7 underwent reduction
      surgery,while 5 had only a laparotomy. ip therapy was well tolerated, and did not
      bring about any postoperative complications even in patients who underwent
      gastrectomy. Although multiple NCI/CTC grade 1 toxicities and grade 2 anemia (4
      of six patients at dose levels 2 and 3) were observed, there was no dose-limiting
      toxicity. The overall median survival time was 316 days, and that for patients
      who underwent gastrectomy was 413 days. Paclitaxel at a dose of 80 mg/m(2) can be
      delivered by the operative ip route with acceptable toxicity profile.

PMID- 17197748
TI  - [Combination chemotherapy with hepatic arterial infusion of 5-fluorouracil (5-FU)
      and systemic irinotecan (CPT-11) in patients with unresectable liver metastases
      from colorectal cancer].
AB  - PURPOSE: Hepatic arterial infusion (HAI) chemotherapy for hepatic metastasis from
      colorectal cancer has higher response rates compared with systemic chemotherapy,
      but can not control extrahepatic lesions. So the combination chemotherapy with
      HAI plus systemic chemotherapy is expected. This study ascertained the efficacy
      and toxicity of combined chemotherapy with HAI plus systemic CPT-11. METHODS:
      Seventeen patients were treated with concurrent HAI 5-FU 700-800 mg/m(2) on day
      1, 8, 15, 22 and systemic CPT-11 70-80 mg/m(2) on day 1 and 15. Treatment was
      repeated every 28 days. RESULTS: The objective response rate for all patients was
      76.5% (13 of 17 patients), and time to progression was about 10 months. Median
      survival time was about 20 months, and no difference was seen in the survival of
      patients without extrahepatic lesions and patients with extrahepatic lesions (21
      months vs 18.5 months; p=0.5). The incidence of new extrahepatic metastasis in
      patients without extrahepatic lesions was 9% (1 of 11 patients). Grade 3 or 4
      neutropenia was found in only 2 patients (11.8%). CONCLUSION: Combination therapy
      with HAI 5-FU plus systemic CPT-11 may be safely administered to patients with
      colorectal cancer. The incidence of new extrahepatic metastases was low in
      comparison with reports of HAI monotherapy.

PMID- 17197750
TI  - [Successful treatment of an elderly patient with pretreated recurrent breast
      cancer using low-dose capecitabine].
AB  - The author reports the successful treatment of an 85-year-old recurrent breast
      cancer patient with low-dose capecitabine. Approximately 20 years ago, the
      patient received a left mastectomy and 2 years later was treated with unspecified
      chemotherapy for bone metastasis. In November 2001, metastatic tumors in thoracic
      vertebrae were removed by emergency laminectomy, followed by radiotherapy plus
      chemotherapy using mitoxantrone, cyclophosphamide and doxifluridine. In June
      2005, abdominal computed tomography revealed a single metastatic tumor 20 mm in
      diameter in the liver. Treatment with paclitaxel at 70 mg/m(2)/day on days 1 and
      14 resulted in no change in tumor size while serum levels of cancer antigen 15-3
      increased from 22.1 to 98.1 U/ml. Subsequent daily treatment with capecitabine at
      1,000 mg/m(2)/day for 21 days was associated with a 50% decrease in tumor size
      and a reduction in serum cancer antigen of 15-3 to 18.8 U/ml. Grade 2 hand-foot
      syndrome was noted,but no severe adverse effects were evident. Five months after
      the induction of capecitabine treatment, a partial response was obtained. These
      results suggest that low-dose capecitabine may be a safe and efficacious
      treatment for elderly patients with pretreated recurrent breast cancer. Clinical
      trials of low-dose capecitabine in such patients are therefore warranted.

PMID- 17197749
TI  - [A case of metastatic lung cancer responding well from tongue carcinoma using a
      combination of stereotactic radiation therapy and docetaxel/cisplatin/5-FU
      chemotherapy].
AB  - A 53-year-old man underwent partial glossectomy for tongue cancer on the right
      side (well-differentiated squamous cell carcinoma T 1 N 0 M 0). One and 9 months
      later, cervical lymph node metastasis was observed bilaterally. After bilateral
      radical neck dissection, 2 courses of NDP/5-FU combined chemotherapy were
      administered. However, 2 metastatic lung cancers were observed 14 months after
      initial treatment. Stereotactic radiation therapy of 50 Gy in 5 fractions and 6
      courses of docetaxel/cisplatin/5-FU chemotherapy were administered. As a result,
      no recurrence was observed, and a complete response was obtained for 41 months
      after lung metastasis.

PMID- 17197751
TI  - [A case of chronic myeloid leukemia following TS-1 therapy for advanced gastric
      cancer].
AB  - A 55-year-old woman had received total gastrectomy for advanced gastric cancer in
      March 2002, and was subsequently treated with adjuvant chemotherapy using oral
      anti-metabolite TS-1 for 21 months. She was well with no evidence of recurrence
      of gastric cancer, but leukocytosis was found in June 2005. The analysis of bone
      marrow revealed that Philadelphia (Ph) chromosome and bcr-abl fusion gene were
      positive. On the basis of these findings, the chronic phase of secondary chronic
      myeloid leukemia (CML) was diagnosed. Three months after being started on
      imatinib therapy, Ph chromosome positive cells disappeared in the bone marrow,
      and a complete cytogenetic response was achieved. Although CML is rare in
      secondary leukemia, this is, to our knowledge, the first reported case of therapy
      related CML following TS-1 treatment. The present case suggested that imatinib
      therapy was also effective for secondary CML as well as de novo CML.

PMID- 17197752
TI  - [A case of hyponatremia associated with combination therapy of systemic
      chemotherapy and paroxetine].
AB  - A 65-year-old woman with relapsed non small cell lung cancer, who had no prior
      chemotherapy, was admitted to our hospital. She was initially treated with
      paroxetine, a selective serotonin-reuptake inhibitor antidepressant, and received
      cisplatin-based chemotherapy three days after the initiation of the paroxetine.
      She developed hyponatremia on day 5 after the start of chemotherapy. Based on the
      laboratory examinations, the syndrome of inappropriate secretion of antiduretic
      hormone was suggested. Her plasma sodium concentration returned to normal after
      paroxetine withdrawal and appropriate fluid restriction. Cisplatin-based
      chemotherapies were subsequently continued without paroxetine and there were no
      further episodes of electrolyte disturbance. Paroxetine has been used widely for
      treatment of depressed patients with malignancies. However, careful monitoring of
      plasma sodium is needed following cisplatin-based chemotherapy in patients taking
      paroxetine.

PMID- 17197753
TI  - [A case of advanced gastric cancer with peritoneal dissemination responding
      remarkably to TS-1/CDDP combination chemotherapy].
AB  - A 57-year-old woman visited a physician with complaints of anorexia and
      pollakiuria. Because a pelvic tumor and ascites were detected, she was referred
      to our department. Douglas pouch puncture revealed adenocarcinoma cells. Further
      examination showed an advanced gastric cancer with peritoneal dissemination. The
      cancer was judged to be unresectable. Chemotherapy with a combination of TS-1 and
      CDDP was performed before the operation. After 2 courses of the chemotherapy, her
      complaints disappeared, although abdominal CT confirmed remaining peritoneal
      dissemination. After 7 courses of chemotherapy, abdominal CT showed that the
      peritoneal dissemination had disappeared. Total gastrectomy and lymph node
      dissection were performed. Histological findings of the stomach revealed complete
      disappearance of cancer cells in the stomach and the regional lymph nodes. We
      confirmed that the TS-1/CDDP therapy resulted in a complete response to advanced
      gastric cancer and peritoneal dissemination. We recommend that chemotherapy be
      continued until the peritoneal dissemination disappears.

PMID- 17197754
TI  - [A case of advanced gastric cancer with multiple liver metastases successfully
      treated with TS-1/low-dose CDDP/lentinan combination chemotherapy].
AB  - We report herein a case of advanced gastric cancer successfully treated with TS
      1/low-dose CDDP/Lentinan combination chemotherapy. A 74-year-old male suffering
      from anorexia was admitted to our hospital and diagnosed as having type 2 gastric
      cancer metastasizing to the liver. TS-1 was orally administered at 100
      mg/body/day for 28 days with a 14-day interval as one session. During the second
      session, because grade 1 thrombocytopenia was noted, administration of TS-1 was
      rescheduled to every other day. CDDP was infused at 10 mg/body/day on day 6 to
      10, 13, 15, and 17. After his discharge, CDDP at 10 mg/body and Lentinan at 2
      mg/body were weekly infused as ambulant patient chemotherapy. The abdominal CT
      scan showed reduction of hepatic tumors by 86% in three months and 97% in 16
      months. Metastatic lymph nodes disappeared in 4 months. The primary tumor was
      reduced and flattened to a cicatrix, and endoscopic biopsy revealed no cancer
      cells. The tumor markers, CEA (716.9 ng/ml) and CA 19-9 (57.2 U/ml), were reduced
      to normal range. The therapeutic efficacy was judged as a partial response (PR),
      which lasted for 16 months without severe adverse effects. He maintained good
      quality of life. This combination chemotherapy was thought to be beneficial for
      patients with advanced gastric cancer.

PMID- 17197755
TI  - [A case of paclitaxel-resistant cancerous ascites secondary to gastric carcinoma
      responding well to TS-1 therapy].
AB  - Paclitaxel was used as the first-line drug for treatment of a case with
      peritoneal recurrence of gastric cancer, accompanied by cancerous ascites.
      Because paclitaxel was ineffective, TS-1 was used as the second-line drug,
      resulting in disappearance of cancerous ascites on diagnostic imaging. This case
      was an 81-year-old male patient. In February 2004, he underwent resection of the
      pyloric side of the stomach (D 2) based on a diagnosis of advanced gastric
      cancer. CT scans, conducted in February 2005, revealed ascites, and a diagnosis
      of cancerous peritonitis was made on the basis of subsequent cyto-diagnostic
      findings. He was later hospitalized because of anorexia and difficulty with oral
      ingestion, and received paclitaxel therapy (60 mg/m(2)). Abdominal CT scans in
      May of the same year showed the disappearance of ascites. Thereafter, he was
      managed as an outpatient. In June of the same year, relapse of ascites was
      detected by CT scans, and exacerbation of ascites was seen in August. In October,
      paclitaxel was switched to TS-1 (80 mg/m(2)). CT scans, obtained at the end of
      two cycles of TS-1 therapy, revealed complete disappearance of ascites. This
      therapy was administered for 4 cycles in total. CT scans, performed at the end of
      each cycle of TS-1 therapy, confirmed the absence of ascites. At present (July
      2006), the patient is managed on an outpatient basis. Our experience with this
      case suggests that if paclitaxel therapy fails to exert satisfactory efficacy,
      switching to second-line TS-1 therapy is a promising means of treating gastric
      cancer complicated by cancerous peritonitis.

PMID- 17197756
TI  - [Complete response in a case of advanced esophageal and gastric double cancer
      treated by chemotherapy of TS-1 and low-dose cisplatin].
AB  - A 78-year-old man was admitted to our hospital complaining of dysphagea on April
      8, 2005. Upper gastrointestinal endoscopic examination showed type 2 esophageal
      cancer in the lower thoracic area and type 3 gastric cancer in the upper body.
      Computed tomography showed No. 3 lymph node swelling, but no distant metastasis.
      Surgery was contraindicated because of many complications, so the patient was
      given combined chemotherapy with TS-1 and low-dose cisplatin. Chemotherapy was
      started on April 18. After 2 courses of chemotherapy the esophageal lesion showed
      a complete response, and after 5 courses the gastric lesion evidenced a complete
      response.

PMID- 17197757
TI  - [A recurrent endocrine cell cancer of the stomach showing almost complete
      remission after chemotherapy for 1 year].
AB  - We report a recurrent case of gastric endocrine cell cancer that showed a
      remarkable response to systemic chemotherapy. A 70-year-old male who underwent
      gastroscopy at our hospital showed a 0-IIa-like lesion, but no abnormal CT
      findings. He was diagnosed with gastric cancer, and underwent a proximal
      gastrectomy. The resected specimen showed endocrine cell cancer. The tumor was
      Grimelius-positive histologically and chromogranin A-and NSE-positive
      immunohistochemically. About 2 years after surgery, liver, lymph node, and bone
      metastases were detected. Systemic chemotherapy with TS-1 and CDDP was started,
      and the lesions progressed. Then, by approximately 1 year after CDDP and CPT-11
      treatments, the recurrent lesions had diminished remarkably and were no longer
      seen on CT or FDG-PET.

PMID- 17197758
TI  - [A case of progressive gastric carcinoma accompanied by disseminated
      carcinomatosis of bone marrow due to bone metastasis with DIC recovery by joint
      administration of 5-FU and paclitaxel].
AB  - A 54-year-old male visited our hospital with the chief complaint of anorexia.
      Based on various tests, a diagnosis of scirrhous gastric carcinoma accompanied by
      bone metastasis and liver metastasis was made. As DIC developed following
      hospital admission, 5-FU and PTX therapy (5-FU at 600 mg/m(2), 24-hour continuous
      infusion, day 1-5 and PTX at 80 mg/m(2), iv, day 8, 15, 22) were administered.
      Although primary foci, bone metastasis, and liver metastasis were observed by
      image diagnostic procedures, recovery from DIC was achieved. 5-FU+PTX therapy is
      considered to be effective for DIC due to bone metastasis of gastric carcinoma.

PMID- 17197759
TI  - [A case of advanced hepatocellular carcinoma with lung metastases and cirrhosis
      that responded to combination chemotherapy with interferon-alpha and 5
      fluorouracil].
AB  - The prognosis for patients with hepatocellular carcinoma (HCC) with progressive
      liver cirrhosis or extrahepatic metastases remains dismal. We report a case of
      HCC with liver cirrhosis and lung metastases who had been treated successfully by
      combination chemotherapy of 5-fluorouracil (5-FU) and interferon-alpha (IFN
      alpha). A 67-year-old male with a history of hepatitis C, liver cirrhosis and HCC
      was hospitalized because of cough and dyspnea. Computed tomography (CT) of chest
      revealed multiple lung metastases. Systemic combination chemotherapy with 5-FU
      and IFN-alpha was begun, and lung metastases disappeared after one course of
      treatment. He died of liver failure one year later, but no recurrence of lung
      metastases was seen. Although systemic combination chemotherapy of 5-FU and IFN
      alpha induced the bone marrow suppression, it was effective for lung metastases
      and palliates symptoms and signs in our case of HCC.

PMID- 17197760
TI  - [Two cases of advanced pancreas cancer treated with GTX: combined use of
      gemcitabine, docetaxel and capecitabine].
AB  - Two cases of advanced pancreas cancer were treated with GTX. One cycle was 3
      weeks, capecitabine (1,000 mg/m(2)/day) was administered from day 1 to 14, and
      GEM 750 mg/m(2) and DOC 30 mg/m(2) were drip-infused on day 4 and 11. A 62-year
      old man with pancreas head cancer and 2 liver metastases was treated with GEM
      1,000 mg/m(2)/week at weeks 1, 2, and 3, and drug-free week 4 for 3 cycles, but
      was PD. After 3 cycles of GTX, the liver metastases decreased in size, and
      thereafter tumor markers became lowest after 7 cycles. The patient was shifted to
      another regimen after 14 cycles for 9 months of GTX. A 75-year-old man with
      pancreas head cancer and vascular invasion has been treated with GTX. As
      leukopenia was seen after the first cycle, the administration doses were reduced
      and GTX has been continued for a total 13 cycles. The tumor reduced in size and
      tumor markers decreased. GTX is suitable for outpatient chemotherapy with mild
      adverse effects.

PMID- 17197762
TI  - [A case of small cell carcinoma in the urinary bladder responding to
      gemcitabine/cisplatin combination therapy as neoadjuvant chemotherapy].
AB  - We report a case of primary small cell carcinoma of the urinary bladder. A 79
      year-old man with the chief complaints of macrohematuria and pollakisuria was
      admitted to our hospital. Cystoscopy and computed tomography (CT) revealed a non
      papillary broad-based bladder tumor. Histological diagnosis was small cell
      carcinoma of the urinary bladder, and he underwent 3 courses of neoadjuvant
      chemotherapy including gemcitabine and cisplatin with a preoperative diagnosis of
      cT3bN0M0. After the chemotherapy, cystoscopy and CT showed complete remission.
      Total cystectomy with ileal conduit was performed following 3 courses of
      chemotherapy. Microscopic examination revealed that the small cell carcinoma had
      disappeared and the converted squamous cell carcinoma remained only in a small
      part of the specimens. The patient was carefully followed for 10 months after
      operation, with no tumor recurrence.

PMID- 17197761
TI  - [Anaphylactic reaction to oxaliplatin--a case of colon cancer].
AB  - Oxaliplatin (L-OHP) is a new third-generation platinum which is efficacious in
      treating advanced unresectable recurrent colorectal cancer as a first-line
      regimen. The marketing authorization was given in Japan in March, 2005. Its
      increased use has resulted in rare serious adverse effects, including
      anaphylactic shock. We experienced a case that developed anaphylactic shock by L
      OHP. We report a 69-year-old man who was treated for recurrent colorectal cancer
      who underwent systemic chemotherapy with FOLFOX 4. After eight cycles he
      developed severe L-OHP associated neuropathy and lung metastases was a
      progressive tendency. The FOLFOX 4 regimen was discontinued and another modality,
      FOLFIRI regimen, was used. After eight cycles of FOLFIRI regimen, lung and liver
      metastases showed progressive disease for response assessment by RECIST criteria.
      Although a patient was stopped L-OHP for neurotoxicity, neuropathy was
      disappeared after 4 months interval. Therefore, we reintroduced L-OHP, FOLFOX 4
      regimen. Anaphylactic shock occurred in the second cycle of reintroduction of the
      FOLFOX 4 regimen (total 10 cycles), 30 minutes after infusion of L-OHP. L-OHP
      infusion was immediately withdrawn and he was treated with intravenous
      hydroxyzine hydrochloride and methylprednisolone. The anaphylaxis symptoms
      resolved in 30 minutes. Chemotherapy based on L-OHP for unresectable recurrence
      colorectal cancer causes anaphylactic shock as a rare severe complication. The
      prediction factor is not proved. We should take steps for early detection of
      anaphylactic reaction and perform the appropriate treatment.

PMID- 17197764
TI  - An intensivist all day, keeps the bad outcomes away.

PMID- 17197765
TI  - Genetics of individualizing patient care.

PMID- 17197766
TI  - Noninvasive ventilation for acute respiratory distress syndrome: breaking down
      the final frontier?

PMID- 17197767
TI  - Inhaled nitric oxide therapy for sepsis: more than just lung.

PMID- 17197768
TI  - About protocols and guidelines: it's time to work in harmony!

PMID- 17197769
TI  - Genetic risk factors for acute respiratory distress syndrome: what's the right
      direction to take?

PMID- 17197770
TI  - Goals for fluid resuscitation: a real challenge.

PMID- 17197771
TI  - Implications of staffing ratios and workload limitations on healthcare-associated
      infections and the quality of patient care.

PMID- 17197772
TI  - Why does cholecystokinin increase in critically ill patients?

PMID- 17197773
TI  - Resistance in the intensive care unit: whose problem is it and how can
      intensivists help?

PMID- 17197774
TI  - B-type natriuretic peptide-guided therapy and prognosis in acutely ill patients
      with pulmonary disease.

PMID- 17197775
TI  - ARDS--shake, rattle, and roll!

PMID- 17197776
TI  - Delirium as destiny: clinical precision and genetic risk.

PMID- 17197777
TI  - Selenium in intensive care: probably not a magic bullet but an important adjuvant
      therapy.

PMID- 17197778
TI  - Nitrogen challenge: are we any closer to achieving a balance?

PMID- 17197779
TI  - Tracheostomy: may the truth be out there?

PMID- 17197780
TI  - One small step for man ...

PMID- 17197781
TI  - Tools that we use: if you can't measure it, you can't manage it.

PMID- 17197782
TI  - Safety culture: is the "unit" the right "unit of analysis"?

PMID- 17197783
TI  - Relation between acute kidney injury and multiple-organ failure: the chicken and
      the egg question.

PMID- 17197784
TI  - Are we ready for MEDS in the ED?

PMID- 17197785
TI  - Is the canary still singing?

PMID- 17197786
TI  - Effect of thoracic epidural anesthesia on right ventricular function and
      homeometric autoregulation.

PMID- 17197787
TI  - The pressure is rising.

PMID- 17197788
TI  - Including families in quality measurement in critical care.

PMID- 17197791
TI  - Pumpless extracorporeal lung assist in patients with acute respiratory distress
      syndrome.

PMID- 17197789
TI  - Risk prediction models: recalibration.

PMID- 17197793
TI  - Selection of sedative for mechanically ventilated patients.

PMID- 17197795
TI  - Patients' and surrogates' perspective on research and testing in critical care.

PMID- 17197796
TI  - About immune-enhancing diets in critically ill patients.

PMID- 17197797
TI  - Randomized control trial of immunosuppression in paraquat poisoning.

PMID- 17197802
TI  - Intermittent therapy for the treatment of chronic HIV infection.

PMID- 17197803
TI  - In a mixed subtype epidemic, the HIV-1 Gag-specific T-cell response is biased
      towards the infecting subtype.
AB  - OBJECTIVES: Southwest Tanzania is affected by an HIV-1 epidemic consisting of
      subtypes A, C, and D, and their recombinant forms. This study was designed to
      assess whether the Gag- and Nef-specific T-cell response is biased towards
      recognizing the infecting subtype. METHODS: The infecting subtypes were
      characterized with a Multi-hybridization assay that discriminates between
      subtypes A, C and D. The interferon-gamma ELISPOT assay was used to detect the
      Gag- and Nef-specific T-cell responses in freshly isolated peripheral blood
      mononuclear cells in 56 seropositive patients. To study the HIV-specific T-cell
      responses, isolate-based Gag and Nef peptide sets representative of the locally
      occurring subtypes were used. The results were analysed at the total protein and
      single peptide level. RESULTS: In the study population, 35% were infected with a
      pure C subtype, 24% and 23% with ACD or AC recombinant forms, respectively. The
      total magnitude (P < 0.01) and breadth (P < 0.01) of the Gag-specific T-cell
      response detected with the subtype C-Gag peptide set was significantly greater
      than that detected with either the subtype A-Gag or D-Gag peptide sets. No
      significant difference was observed in the Nef-specific response. In 85% of
      responses targeting the most immunodominant Gag epitopes with subtype-specific
      sequence differences, the best recognized epitope variant corresponded to the
      infecting subtype. CONCLUSIONS: The Gag-specific T-cell response had a preference
      for recognizing peptides related to the infecting subtype.

PMID- 17197804
TI  - Reduction in mother-to-child transmission of HIV in Thailand, 2001-2003: Results
      from population-based surveillance in six provinces.
AB  - BACKGROUND: In 2000, Thailand implemented a national program to prevent mother-to
      child HIV transmission (PMTCT). OBJECTIVE: To describe the effectiveness of the
      prevention of mother-to-child HIV transmission program in Thailand. DESIGN AND
      METHODS: A register of HIV-exposed children at birth was created with follow-up
      of infection status. The register included children born to HIV-infected women
      between 1 January 2001 and 31 December 2003 at 84 public health hospitals in six
      provinces of Thailand. The main outcome measure was HIV infection in children.
      RESULTS: A total of 2200 children born to HIV-infected mothers were registered.
      Of these mother-infant pairs, 2105 (95.7%) received some antiretroviral
      prophylaxis, including 1358 (61.7%) who received the complete short-course
      zidovudine regimen during pregnancy and labor for the mother and after birth for
      the infant, with or without other antiretrovirals. HIV infection outcome was
      determined for 1667 (75.8%) children, of whom 158 [9.5%, 95% confidence interval
      (CI), 8.1-11.0%] were infected. Transmission risk was 6.8% (95% CI 5.2-8.9%)
      among 761 mother-infant pairs that received the complete zidovudine regimen
      alone, and 3.9% (95% CI, 2.2-6.6%) among 361 mother-infant pairs that received
      the complete zidovudine regimen combined with other antiretrovirals, usually
      nevirapine. The overall transmission risk from this cohort, including all
      antiretroviral prophylaxis combinations, is estimated to be 10.2%. CONCLUSIONS:
      The Thai national PMTCT program is effective in reducing mother-to-child
      transmission risk from the historical risk of 18.9-24.2%. The addition of
      nevirapine to short-course zidovudine beginning in 2004 may further improve
      program effectiveness in Thailand.

PMID- 17197805
TI  - Early archives of genetically-restricted proviral DNA in the female genital tract
      after heterosexual transmission of HIV-1.
AB  - OBJECTIVES AND METHOD: In order to characterize human immunodeficiency virus type
      1 (HIV-1) variants that are transmitted in women via heterosexual intercourse,
      the env V1-V3 sequences of HIV-1 provirus (DNA) and free virus (RNA) in paired
      samples of blood and cervicovaginal secretions of untreated chronically and
      primary infected African women were compared. RESULTS: Env RNA sequences
      retrieved from plasma and genital compartments formed a single cluster in primary
      infection. In contrast, env RNA sequences from these two compartments were
      distinct in chronically infected women. Analysis of proviral DNA of primary
      infected women showed that most HIV-1 sequences derived from the genital
      epithelia form independent clusters from HIV-1 sequences of DNA from peripheral
      blood mononuclear cells and RNA recovered from plasma and genital secretions.
      Similarly, the analysis of proviral DNA in the genital compartment of chronically
      infected women showed the persistence of genetically-restricted cluster of HIV-1.
      CONCLUSIONS: These observations indicate that a viral subpopulation is archived
      as proviral DNA in the female genital tract early in primary infection, and
      suggest that HIV-1 variants from the male donor are selected in the female
      mucosal site during male to female transmission of HIV-1.

PMID- 17197806
TI  - Determination of simian immunodeficiency virus production by infected activated
      and resting cells.
AB  - OBJECTIVE: To determine the relative amount of virus produced by activated and
      resting CD4+ T cells. DESIGN: The total quantity of virus produced by an
      activated cell relative to a resting cell in vivo was estimated from 'snap-shots'
      of virus production by infected cells at one time point. METHODS: Bayesian
      statistical methods were used to determine a credible interval for the desired
      ratio. RESULTS: The posterior mean of the ratio of virus produced by a typical
      activated cell to a typical resting cell is 0.82 to 4.28, depending on the half
      lives of the resting infected cells. Simian immunodeficiency virus-infected
      resting cells could accordingly be responsible for 70 to 93% of peak virus
      production in the acute stage of infection. CONCLUSIONS: Whereas in 'snap-shots'
      the infected resting cells apparently produce much less virus than infected
      activated CD4+ T cells, the coincidence of peak SIV production with predominant
      infection of resting cells along with longer half-lives for productively infected
      resting cells point to a major contribution to virus production in early
      infection.

PMID- 17197807
TI  - Antiretroviral therapy interruption guided by CD4 cell counts and plasma HIV-1
      RNA levels in chronically HIV-1-infected patients.
AB  - OBJECTIVE: We evaluated the safety of CD4 cell count and plasma HIV-1 RNA (pVL)
      guided treatment interruptions (GTI) and determined predictors of duration of
      treatment interruption. METHODS: Chronically HIV-1-infected adults with sustained
      CD4 cell counts > 500 cells/microl and pVL < 50 copies/ml were randomly assigned
      to either continue with standard antiretroviral therapy (control group, n = 101)
      or to interrupt therapy aimed at maintaining CD4 cell counts > 350 cells/microl
      and pVL < 100,000 copies/ml (GTI group, n = 100). Both groups were followed for 2
      years. RESULTS: There were no AIDS-defining illnesses or deaths in either group.
      Compared to controls, subjects interrupting therapy reduced treatment exposure by
      67%, but suffered significantly more adverse events related to the intake of
      medication or to therapy interruption [relative hazard, 2.71; 95% confidence
      interval (CI), 1.64-4.49; P < 0.001), mainly due to an excess in mononucleosis
      like symptoms. While GTI subjects demonstrated improvements in the psychosocial
      spheres of quality of life and pain reporting, GTI had no effect on the physical
      aspects of quality of life. Although both groups had a similar hazard for
      developing CD4 cell count < 200 cells/microl; at least 10% of subjects on GTI had
      CD4 cell counts < 350 cells/microl at every time point. Drug resistance mutations
      were detected in 36% of subjects but were selected de novo only in subjects
      interrupting non-nucleoside reverse transcriptase inhibitor therapy. Lower CD4
      cell count nadir, higher set-point pVL and prior exposure to suboptimal regimens
      were all independent predictors of the need to reinitiate treatment. CONCLUSIONS:
      Overall, GTI were not as safe as continuing therapy. Despite achieving some
      improvements in quality of life, GTI did not reduce the overall rate of
      management-related adverse events.

PMID- 17197808
TI  - Food and Drug Administration analysis of tipranavir clinical resistance in HIV-1
      infected treatment-experienced patients.
AB  - OBJECTIVE: To assess the resistance profile of tipranavir. METHODS: Resistance
      analyses were performed on Boehringer Ingelheim-sponsored studies examining the
      safety and efficacy of tipranavir in highly treatment-experienced individuals at
      24 weeks. Virologic response rates based on the presence of baseline primary
      protease inhibitor mutations and based on baseline tipranavir susceptibility were
      evaluated, and the development of protease mutations during treatment with
      tipranavir was analyzed. RESULTS: Virologic response rates in tipranavir-treated
      individuals were reduced when isolates with substitutions at amino acid positions
      I13, V32, M36, I47, Q58, D60 V82 or I84 were present at baseline. In addition,
      virologic response rates to tipranavir decreased when the number of baseline
      protease inhibitor (PI) mutations was five or more. Individuals who received
      tipranavir without concomitant enfurvitide and had five or more baseline PI
      mutations group began to lose antiviral response between weeks 4 and 8. However,
      individuals taking enfuvirtide with tipranavir were able to achieve greater than
      1.5 log10 reductions in viral load from baseline out to 24 weeks even if they had
      five or more baseline PI mutations. Virologic response rates to tipranavir
      decreased when the baseline phenotype for tipranavir had a greater than three
      fold shift in the 50% effective concentration (EC50) from reference. The most
      common protease mutations that developed in tipranavir-treated individuals who
      experienced virologic failure were L10I/V/S, I13V, L33V/I/F, M36V/I/L V82T, V82L,
      and I84V. The resistance profile in treatment-naive individuals was not
      characterized. CONCLUSIONS: Baseline genotypic and phenotypic data provide
      valuable information on the likelihood of a virologic response to tipranavir.

PMID- 17197809
TI  - Nodular regenerative hyperplasia is a new cause of chronic liver disease in HIV
      infected patients.
AB  - OBJECTIVE: To describe and explain the syndrome of HIV-associated cryptogenic
      liver disease in eight consecutive patients suffering from portal hypertension.
      METHODS: The study was undertaken at a liver disease centre in Paris and involved
      eight of 97 consecutive HIV-infected patients presenting abnormal liver function
      tests and/or symptomatic portal hypertension of unknown origin. Serology,
      pathology, and liver function tests were performed. RESULTS: A clear nodular
      architecture corresponding to nodular regenerative hyperplasia was observed in
      seven patients and suggested in one, based on the presence of sinusoidal
      dilatation in a clinical context of portal hypertension, without overt liver
      disease. CONCLUSIONS: Nodular regenerative hyperplasia appears to be a new cause
      of portal hypertension in HIV-infected patients. This syndrome can be of critical
      importance as patients can be exposed to the significant complications of portal
      hypertension and to refractory ascites which may require liver transplantation.

PMID- 17197810
TI  - The association between hepatitis C infection and prevalent cardiovascular
      disease among HIV-infected individuals.
AB  - OBJECTIVE: To examine the association between hepatitis C and prevalent
      cardiovascular disease (CVD) among HIV-infected individuals. DESIGN: A cross
      sectional analysis of data from the HIV-Longitudinal Interrelationships of
      Viruses and Ethanol (HIV-LIVE) cohort, a prospective cohort of HIV-infected
      individuals with current or past alcohol problems. METHODS: We analysed health
      questionnaire and laboratory data from 395 HIV-infected individuals (50.1% co
      infected with hepatitis C) using logistic regression to estimate the odds ratio
      (OR) for the prevalence of CVD among those co-infected with hepatitis C and HIV
      compared with those infected with HIV alone. RESULTS: The prevalence of CVD was
      higher among those co-infected with hepatitis C compared with those with HIV
      alone (11.1 versus 2.5%, respectively). After adjusting for age, the OR for the
      prevalence of CVD was significantly higher among those with hepatitis C co
      infection (adjusted OR 4.65, 95% confidence interval 1.70-12.71). The
      relationship between hepatitis C and CVD persisted when adjusting for age and
      other sociodemographic characteristics, substance use, and cardiovascular risk
      factors in separate regression models. CONCLUSION: Co-infection with hepatitis C
      among a cohort of HIV-infected individuals was associated with a higher age
      adjusted odds for the prevalence of CVD. These data suggest that hepatitis C
      infection may be associated with an increased risk of CVD among those co-infected
      with HIV.

PMID- 17197811
TI  - Drug resistance among HIV-infected pregnant women receiving antiretrovirals for
      prophylaxis.
AB  - OBJECTIVE: To quantify primary resistance mutations (PRMs) among HIV-1-infected
      women receiving antiretroviral therapy (ART) for prevention of mother-to-child
      transmission (MTCT). METHODS: Peripheral blood mononuclear cell samples from HIV
      1-infected women enrolled in a prospective cohort study in Argentina, the
      Bahamas, Brazil, and Mexico (NISDI Perinatal Study) were assayed for PRMs.
      Eligible women were those enrolled by March 2005 and diagnosed with HIV-1
      infection during the current pregnancy, and who received ART for MTCT prophylaxis
      and were followed for 6-12 weeks postpartum. RESULTS: Of 819 women, 198 met the
      eligibility criteria. At enrollment, 98% were asymptomatic, 62% had plasma viral
      load < 1000 copies/ml, 53% had CD4+ cell count > or = 500 cells/microl, and 78%
      were ART-exposed (mean duration, 8.0 weeks; 95% confidence interval, 7.1-8.9).
      The most complex ART regimen during pregnancy was usually (81%) a three-drug
      regimen [two nucleoside reverse transcriptase inhibitors (NRTIs) + one protease
      inhibitor or two NRTIs + one non-nucleoside reverse transcriptase inhibitor).
      PRMs were observed in samples from 19 (16%) of 118 women that were amplifiable at
      one or both time points [11/76 (14%) at enrollment; 14/97 (14%) at 6-12 weeks].
      The occurrence of PRMs was not associated with clinical, immunological, or
      virological disease stage at either time point, whether ART-naive versus exposed
      at enrollment, or the most complex or number of antiretroviral drug regimens
      received during pregnancy (P > 0.1). Of 55 women with amplifiable samples at both
      time points, PRMs were detected in 11 samples (20%). CONCLUSIONS: PRMs occurred
      among 16.1% of relatively healthy HIV-1-infected mothers from Latin American and
      Caribbean countries receiving MTCT prophylaxis.

PMID- 17197812
TI  - Elevated risk of lung cancer among people with AIDS.
AB  - BACKGROUND AND OBJECTIVES: Lung cancer is a common malignancy among people with
      AIDS (PWA). Lung cancer risk was compared between PWA and the general population
      and its relationship with immunosuppression was assessed. The likelihood that
      excess risk is explained by a high prevalence of smoking was also investigated.
      METHODS: Records on adolescent and adult PWA (N = 397 927) were linked with
      cancer registries in 11 US regions. Cancer risk was assessed for the period 60
      months before to 60 months after AIDS onset, with specific emphasis on the period
      4-27 months after onset. Observed incidence was compared with general population
      rates and rates from a lung cancer prediction model for smokers. RESULTS:
      Compared with the general population, lung cancer risk among PWA was elevated
      overall [n = 1489 cases; standardized incidence ratio (SIR), 3.8; 95% confidence
      interval (CI), 3.6-4.1] and in the 4-27 months after AIDS (n = 393 cases; SIR,
      2.9; 95% CI, 2.6-3.2). In the 4-27 months after AIDS, risk was significantly
      elevated for all demographic subgroups, and was especially high among young PWA
      (SIRs for ages 15-29 years, 10.4; 30-39 years, 6.3; 40-49 years, 3.7). Lung
      cancers generally presented at an advanced stage. Risk was not associated with
      CD4 cell counts at AIDS (Ptrend = 0.36). Under plausible smoking assumptions,
      observed incidence was significantly higher than predicted among 40-49 and 50-59
      year-old men with AIDS (observed/predicted = 5.03 and 1.43, respectively) and 40
      49-year-old women with AIDS (observed/predicted = 1.88), but not among older PWA.
      CONCLUSION: Lung cancer risk was substantially elevated among PWA. Smoking could
      not entirely account for the observed elevation, especially among younger adults,
      suggesting a role for additional co-factors.

PMID- 17197813
TI  - HIV-1 protease and reverse transcriptase mutations for drug resistance
      surveillance.
AB  - OBJECTIVES: Monitoring regional levels of transmitted HIV-1 resistance informs
      treatment guidelines and provides feedback on the success of HIV-1 prevention
      efforts. Surveillance programs for estimating the frequency of transmitted
      resistance are being developed in both industrialized and resource-poor
      countries. However, such programs will not produce comparable estimates unless a
      standardized list of drug-resistance mutations is used to define transmitted
      resistance. METHODS: In this paper, we outline considerations for developing a
      list of drug-resistance mutations for epidemiologic estimates of transmitted
      resistance. First, the mutations should cause or contribute to drug resistance
      and should develop in persons receiving antiretroviral therapy. Second, the
      mutations should not occur as polymorphisms in the absence of therapy. Third, the
      mutation list should be applicable to all group M subtypes. Fourth, the mutation
      list should be simple, unambiguous, and parsimonious. RESULTS: Applying these
      considerations, we developed a list of 31 protease inhibitor-resistance mutations
      at 14 protease positions, 31 nucleoside reverse transcriptase inhibitor
      resistance mutations at 15 reverse transcriptase positions, and 18 non-nucleoside
      reverse transcriptase inhibitor-resistance mutations at 10 reverse transcriptase
      positions. CONCLUSIONS: This list, which should be updated regularly using the
      same or similar criteria, can be used for genotypic surveillance of transmitted
      HIV-1 drug resistance.

PMID- 17197814
TI  - HLA-B Bw4 alleles and HIV-1 transmission in heterosexual couples.
AB  - BACKGROUND: Genetic factors may play a role in the transmission of HIV-1. Because
      HLA-B alleles influence HIV-1 disease progression and viral levels, they might
      also influence HIV-1 transmission. OBJECTIVE: To investigate if the presence of
      HLA-B alleles with the Bw4 epitope in HIV-1-infected men decreased the risk of
      transmission to their female sex partners. METHODS: The study comprised 304 HIV-1
      infected men with hemophilia and 325 female sex partners. HLA class I genes were
      amplified using sequence-specific primers. Products of the polymerase chain
      reaction were blotted on nylon membranes and hybridized with sequence-specific
      oligonucleotide probes. Logistic regression models were used to calculate odds
      ratios (OR) and 95% confidence intervals (CI) for HIV-1 infection among the
      women. RESULTS: Among the 325 women, 44 (13.5%) were infected with HIV-1. HIV-1
      infection in the women was associated with the HLA-B genotype of their male
      partner [Bw6/Bw6, 22/118 (18.6%); Bw4/Bw6, 18/154 (11.7%); Bw4/Bw4, 4/53 (7.6%)].
      Compared with men who were homozygous for Bw6, men who carried Bw4 were about
      half as likely to have transmitted HIV-1 to their female partner (OR, 0.52; 95%
      CI, 0.27-0.98; P = 0.04). Transmission was higher among couples in which the
      man's ethnicity was other than White (OR, 2.60; 95% CI, 1.25-5.40; P = 0.01), but
      the association between HIV-1 transmission and HLA-B genotype was not confounded
      by race. CONCLUSION: The presence of HLA-Bw4 in HIV-1-infected men was associated
      with a decreased risk of male-to-female HIV-1 transmission, which suggests that
      these alleles reduce infectivity for HIV-1.

PMID- 17197815
TI  - Convergence of HIV seroprevalence among injecting and non-injecting drug users in
      New York City.
AB  - OBJECTIVE: To compare HIV prevalence among injecting and non-injecting heroin and
      cocaine users in New York City. As HIV is efficiently transmitted through the
      sharing of drug-injecting equipment, HIV infection has historically been higher
      among injecting drug users. DESIGN: Two separate cross-sectional surveys, both
      with HIV counseling and testing and drug use and HIV risk behavior
      questionnaires. METHODS: Injecting and non-injecting heroin and cocaine users
      recruited at detoxification and methadone maintenance treatment from 2001-2004 (n
      = 2121) and recruited through respondent-driven sampling from a research
      storefront in 2004 (n = 448). RESULTS: In both studies, HIV prevalence was nearly
      identical among current injectors (injected in the last 6 months) and heroin and
      cocaine users who had never injected: 13% [95% confidence interval (CI), 12-15%]
      among current injectors and 12% (95% CI, 9-16%) among never-injectors in the drug
      treatment program study, and 15% (95% CI, 11-19%) among current injectors and 17%
      (95% CI, 12-21%) among never injectors in the respondent driven sampling
      storefront study. The 95% CIs overlapped in all gender and race/ethnicity
      subgroup comparisons of HIV prevalence in both studies. CONCLUSIONS: The very
      large HIV epidemic among drug users in New York City appears to be entering a new
      phase, in which sexual transmission is of increasing importance. Additional
      prevention programs are needed to address this transition.

PMID- 17197816
TI  - Prevalence of primary genotypic resistance in a UK centre: Comparison of primary
      HIV-1 and newly diagnosed treatment-naive individuals.
AB  - The worrying finding that up to 19% of newly diagnosed HIV-1 cases in the UK have
      genotypic evidence of transmitted drug-resistant HIV-1 (TrDR-HIV-1) does not
      concur with levels observed in one London centre. A study of the prevalence of
      resistance in primary HIV infection and newly diagnosed antiretroviral-naive
      individuals demonstrated significantly lower levels of TrDR-HIV-1 than previously
      reported. Variations in the prevalence of TrDR-HIV-1 may reflect the
      heterogeneity of methodologies and definitions used for resistance.

PMID- 17197818
TI  - Salvage therapy with amprenavir, lopinavir and ritonavir is durably potent in HIV
      infected patients in virological failure: 1-year results.
AB  - We report the results of the extended follow-up at one year of a randomized trial
      evaluating the virological efficacy of a salvage therapy combining lopinavir and
      amprenavir with either 200 or 400 mg/day ritonavir, along with optimized
      nucleoside reverse transcriptase inhibitors, in patients carrying multidrug
      resistant isolates. The combination of amprenavir, lopinavir and ritonavir (400
      mg/day) is durably potent, yielding a sustained virological response (HIV RNA <
      50 copies) in 39% of cases.

PMID- 17197817
TI  - Frequent methamphetamine use is associated with primary non-nucleoside reverse
      transcriptase inhibitor resistance.
AB  - We determined whether methamphetamine use is associated with the increased
      prevalence of primary HIV drug resistance among a cohort of men who have sex with
      men recently infected with HIV. In multivariate analysis, we found that frequent
      methamphetamine use was strongly associated with primary non-nucleoside reverse
      transcriptase inhibitor resistance, but not with protease inhibitor or nucleoside
      reverse transcriptase inhibitor resistance. We postulate that this association
      may be caused by methamphetamine-associated treatment interruptions among source
      partners.

PMID- 17197819
TI  - No evidence of an increase in serosorting with casual partners among HIV-negative
      gay men in London, 1998-2005.
AB  - Serosorting is an HIV risk reduction strategy whereby some gay men only engage in
      unprotected anal intercourse with casual partners of the same HIV status. There
      was no evidence of an increase in serosorting among HIV-negative gay men in
      London between 1998 and 2005 (1.7%, 1.2%; test for a trend P = 0.1). By way of
      comparison, the percentage of HIV-positive gay men who reported serosorting more
      than doubled during this time (6.8%, 17.7%, P < 0.01).

PMID- 17197820
TI  - Immune activation and normal levels of endogenous antivirals are seen in healthy
      adolescents born of HIV-infected mothers.
AB  - Immunological analyses performed in healthy adolescents born of HIV-infected
      (seroreverters) or healthy mothers (healthy controls; HC) showed that immune
      activation and a skewing of postthymic differentiation are present in adolescent
      seroreverters. In-utero HIV exposure results in long-lasting imprinting on the
      immune system. Alternatively, an immune response naturally more prone to
      activation could prevent vertical infection. Endogenous antivirals (APOBEC,
      TRIM5alpha) were comparable in seroreverters and HC, and might not play a role in
      resistance to vertical HIV infection.

PMID- 17197821
TI  - Genetic diversity and population structure of Mycobacterium tuberculosis in HIV-1
      infected compared with uninfected individuals in Burkina Faso.
AB  - HIV-1 infection and HIV-1-induced immune deficiency may play a role in selecting
      particular Mycobacterium tuberculosis (MTB) strains (i.e. genotypes). We compared
      43 MTB isolates obtained from HIV-1-infected patients with 77 MTB isolates
      obtained from HIV-1-uninfected patients in Burkina Faso, by means of DNA
      fingerprinting methods (MIRU-VNTR plus spoligotyping). This study suggests a lack
      of structure of the MTB population caused by HIV-1 infection and a similar
      genetic diversity of MTB in HIV-1-infected compared with uninfected individuals.

PMID- 17197822
TI  - CD8 T-cell subsets and viral load in the cerebrospinal fluid of therapy-naive HIV
      infected individuals.
AB  - Central nervous system involvement is common in HIV infection. We determined the
      relationship between T-cell subsets and viral load in the cerebrospinal fluid
      (CSF) of therapy-naive, asymptomatic HIV-infected individuals. A shift from naive
      to effector-memory CD8 T cells was observed in the CSF of HIV-infected
      individuals compared with controls. The HIV load strongly correlated with CD8 T
      cells in CSF. Effector-memory CD8 T cells were positively and effector CD8 T
      cells were negatively associated with viral replication in CSF.

PMID- 17197823
TI  - HIV-hepatitis C virus co-infection is associated with decreased plasmatic IL-7
      levels.
AB  - We analysed the potential influence of hepatitis C virus (HCV) co-infection over
      IL-7 levels and thymic function in naive HIV-infected patients and after
      effective HAART. HIV-HCV-co-infected patients had lower plasmatic IL-7 levels
      compared with HIV-monoinfected patients. This effect may not be associated either
      with HCV monoinfection or with the rate of liver injury. These lower levels may
      explain, at least partly, the lower CD4 cell repopulation of HIV-HCV-co-infected
      patients after HAART.

PMID- 17197824
TI  - Efavirenz-associated podocyte damage.

PMID- 17197825
TI  - Continued correspondence 'Will ART rollout in Africa drive an epidemic of drug
      resistant HIV?'.

PMID- 17197827
TI  - Rapid scaling-up of access to antiretroviral therapy in Mexico: Is it better not
      to treat?

PMID- 17197828
TI  - Late HIV seroconversion after non-occupational postexposure prophylaxis against
      HIV with concomitant hepatitis C virus seroconversion.

PMID- 17197829
TI  - Relapse of HIV-associated nephropathy after discontinuing highly active
      antiretroviral therapy.

PMID- 17197830
TI  - HLA-Cw8 primarily associated with hypersensitivity to nevirapine.

PMID- 17197831
TI  - K65R development among subtype C HIV-1-infected patients in tenofovir DF clinical
      trials.

PMID- 17197832
TI  - Reporting deficiencies in trials of abstinence-only programmes for HIV
      prevention.

PMID- 17197833
TI  - Severe liver toxicity in postexposure prophylaxis for HIV infection with a
      zidovudine, lamivudine and fosamprenavir/ritonavir regimen.

PMID- 17197840
TI  - Intravenous lidocaine infusion facilitates acute rehabilitation after
      laparoscopic colectomy.
AB  - BACKGROUND: Intravenous infusion of lidocaine decreases postoperative pain and
      speeds the return of bowel function. The authors therefore tested the hypothesis
      that perioperative lidocaine infusion facilitates acute rehabilitation protocol
      in patients undergoing laparoscopic colectomy. METHODS: Forty patients scheduled
      to undergo laparoscopic colectomy were randomly allocated to receive intravenous
      lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia,
      then a continuous infusion of 2 mg.kg.h intraoperatively and 1.33 mg.kg.h for 24
      h postoperatively) or an equal volume of saline. All patients received similar
      intensive postoperative rehabilitation. Postoperative pain scores, opioid
      consumption, and fatigue scores were measured. Times to first flatus, defecation,
      and hospital discharge were recorded. Postoperative endocrine (cortisol and
      catecholamines) and metabolic (leukocytes, C-reactive protein, and glucose)
      responses were measured for 48 h. Data (presented as median [25-75% interquartile
      range], lidocaine vs. saline groups) were analyzed using Mann-Whitney tests.
      P<0.05 was considered statistically significant. RESULTS: Patient demographics
      were similar in the two groups. Times to first flatus (17 [11-24] vs. 28 [25-33]
      h; P<0.001), defecation (28 [24-37] vs. 51 [41-70] h; P=0.001), and hospital
      discharge (2 [2-3] vs. 3 [3-4] days; P=0.001) were significantly shorter in
      patients who received lidocaine. Lidocaine significantly reduced opioid
      consumption (8 [5-18] vs. 22 [14-36] mg; P=0.005) and postoperative pain and
      fatigue scores. In contrast, endocrine and metabolic responses were similar in
      the two groups. CONCLUSIONS: Intravenous lidocaine improves postoperative
      analgesia, fatigue, and bowel function after laparoscopic colectomy. These
      benefits are associated with a significant reduction in hospital stay.

PMID- 17197841
TI  - Racial differences in the use of epidural analgesia for labor.
AB  - BACKGROUND: There is strong evidence that pain is undertreated in black and
      Hispanic patients. The association between race and ethnicity and the use of
      epidural analgesia for labor is not well described. METHODS: Using the New York
      State Perinatal Database, the authors examined whether race and ethnicity were
      associated with the likelihood of receiving epidural analgesia for labor after
      adjusting for clinical characteristics, demographics, insurance coverage, and
      provider effect. This retrospective cohort study was based on 81,883 women
      admitted for childbirth between 1998 and 2003. RESULTS: Overall, 38.3% of the
      patients received epidural analgesia for labor. After adjusting for clinical risk
      factors, socioeconomic status, and provider fixed effects, Hispanic and black
      patients were less likely than non-Hispanic white patients to receive epidural
      analgesia: The adjusted odds ratio was 0.85 (95% CI, 0.78-0.93) for
      white/Hispanic and 0.78 (0.74-0.83) for blacks compared with non-Hispanic whites.
      Compared with patients with private insurance, patients without insurance were
      least likely to receive epidural analgesia (adjusted odds ratio, 0.76; 95% CI,
      0.64-0.89). Black patients with private insurance had similar rates of epidural
      use to white/non-Hispanic patients without insurance coverage: The adjusted odds
      ratio was 0.66 (95% CI, 0.53-0.82) for white/non-Hispanic patients without
      insurance versus 0.69 (0.57-0.85) for black patients with private insurance.
      CONCLUSION: Black and Hispanic women in labor are less likely than non-Hispanic
      white women to receive epidural analgesia. These differences remain after
      accounting for differences in insurance coverage, provider practice, and clinical
      characteristics.

PMID- 17197842
TI  - Late psychological symptoms after awareness among consecutively included surgical
      patients.
AB  - BACKGROUND: Awareness during general anesthesia can cause late psychological
      symptoms. Selection bias may have affected the results in previous retrospective
      studies. The authors used prospective consecutive collection to recruit patients
      with previous awareness. METHODS: In a cohort of 2,681 consecutive patients
      scheduled to undergo general anesthesia, 98 considered themselves to have been
      aware during previous surgery. Six patients died before inclusion, and another 13
      were excluded (4 cases of stroke or dementia, 7 declined to participate, and 2
      could not be located). Seventy-nine patients were interviewed by telephone, and
      medical records were checked in uncertain cases. The interview followed a
      structured protocol, including seven late symptoms (anxiety, chronic fear,
      nightmares, flashbacks, indifference, loneliness, and lack of confidence in
      future life). Three persons independently assessed the interviews for
      classification, to determine whether awareness had occurred. RESULTS: Four cases
      were performed using regional anesthesia, and another 29 were not considered as
      awareness by the assessors. Therefore, the final analyses included 46 patients.
      Twenty (43%) had experienced pain, and 30 (65%) described acute emotional
      reactions during the awareness episode. Fifteen (33%) patients had experienced
      late psychological symptoms afterward. In 6 of those cases, the symptoms lasted
      for more than 2 months, and 1 patient had a diagnosis of post-traumatic stress
      disorder. Acute emotional reactions were significantly related to late
      psychological symptoms (P<0.05). CONCLUSION: The method for recruiting awareness
      cases in studies on late psychological symptoms may affect the result. The
      authors found fewer and milder problems, despite a similar degree of initial
      problems as in previous studies.

PMID- 17197843
TI  - Dreaming during anesthesia and anesthetic depth in elective surgery patients: a
      prospective cohort study.
AB  - BACKGROUND: Dreaming reported after anesthesia remains a poorly understood
      phenomenon. Dreaming may be related to light anesthesia and represent near-miss
      awareness. However, few studies have assessed the relation between dreaming and
      depth of anesthesia, and their results were inconclusive. Therefore, the authors
      tested the hypothesis that dreaming during anesthesia is associated with light
      anesthesia, as evidenced by higher Bispectral Index values during maintenance of
      anesthesia. METHODS: With approval, 300 consenting healthy patients, aged 18-50
      yr, presenting for elective surgery requiring relaxant general anesthesia with a
      broad range of agents were studied. Patients were interviewed on emergence and 2
      4 h postoperatively. The Bispectral Index was recorded from induction until the
      first interview. Dream content and form were also assessed. RESULTS: Dreaming was
      reported by 22% of patients on emergence. There was no difference between
      dreamers and nondreamers in median Bispectral Index values during maintenance (37
      [23-55] vs. 38 [20-59]; P=0.68) or the time at Bispectral Index values greater
      than 60 (0 [0-7] vs. 0 [0-31] min; P=0.38). Dreamers tended to be younger and
      male, to have high home dream recall, to receive propofol maintenance or regional
      anesthesia, and to open their eyes sooner after surgery. Most dreams were similar
      to dreams of sleep and were pleasant, and the content was unrelated to surgery.
      CONCLUSIONS: Dreaming during anesthesia is unrelated to the depth of anesthesia
      in almost all cases. Similarities with dreams of sleep suggest that anesthetic
      dreaming occurs during recovery, when patients are sedated or in a physiologic
      sleep state.

PMID- 17197844
TI  - Pharmacokinetics of ropivacaine in patients with chronic end-stage liver disease.
AB  - BACKGROUND: Ropivacaine is mainly eliminated by hepatic metabolism. The authors
      studied the effect of chronic end-stage liver disease on the pharmacokinetics of
      ropivacaine. METHODS: Thirteen patients with chronic end-stage liver disease and
      eight healthy volunteers received a single dose of 0.6 mg/kg ropivacaine
      intravenously over 30 min. Ropivacaine, 3-hydroxyropivacaine, and 2',6'
      pipecoloxylidide were measured in venous plasma and urine. RESULTS: Peak
      ropivacaine plasma concentrations were similar. Patients with chronic end-stage
      liver disease had, on average, 60% lower total (P=0.001) and 56% lower unbound
      plasma clearance (P=0.002), 59% higher steady state volume of distribution
      (P=0.03), and 4.2-fold longer half-life (P<0.001) of ropivacaine. Of the
      variation in total ropivacaine clearance, 69% was accounted for by variation in
      albumin, 57% in prealbumin, 25% in international normalized ratio of plasma
      thromboplastin time, and 24% in galactose half-life. The patients excreted a
      larger fraction of the original dose as unchanged ropivacaine (2.1% vs. 0.3%;
      P<0.001) and a smaller fraction as 3-hydroxyropivacaine (11% vs. 27%; P=0.001).
      The fraction excreted as 2',6'-pipecoloxylidide (4.7% vs. 5.0%) was similar.
      CONCLUSIONS: Ropivacaine clearance is decreased in chronic end-stage liver
      disease. A normal dose can be considered for a single block in patients with
      liver impairment, because the peak plasma concentrations were essentially
      similar. When using a postoperative ropivacaine infusion in a patient with end
      stage liver disease, the lowest effective dose should be used for the shortest
      possible time and the patient should be monitored closely, because systemic
      toxicity cannot be ruled out. Because of wide interindividual differences in
      pharmacokinetics in patients with liver disease, no definitive dosing
      instructions can be given.

PMID- 17197845
TI  - A randomized crossover comparison of the effects of propofol and sevoflurane on
      cerebral hemodynamics during carotid endarterectomy.
AB  - BACKGROUND: Intravenous and inhalational anesthetic agents have differing effects
      on cerebral hemodynamics: Sevoflurane causes some vasodilation, whereas propofol
      does not. The authors hypothesized that these differences affect internal carotid
      artery pressure (ICAP) and the apparent zero flow pressure (critical closing
      pressure) during carotid endarterectomy. Vasodilation is expected to increase
      blood flow, reduce ICAP, and reduce apparent zero flow pressure. METHODS: In a
      randomized crossover study, the gradient between systemic arterial pressure and
      ICAP during carotid clamping was measured while changing between sevoflurane and
      propofol in 32 patients. Middle cerebral artery blood velocity, recorded by
      transcranial Doppler, and ICAP waveforms were analyzed to determine the apparent
      zero flow pressure. RESULTS: ICAP increased when changing from sevoflurane to
      propofol, causing the mean gradient between arterial pressure and ICAP to
      decrease by 10 mmHg (95% confidence interval, 6-14 mmHg; P<0.0001). Changing from
      propofol to sevoflurane had the opposite effect: The pressure gradient increased
      by 5 mmHg (95% confidence interval, 2-7 mmHg; P=0.002). Ipsilateral middle
      cerebral artery blood velocity decreased when changing from sevoflurane to
      propofol. Cerebral steal was detected in one patient after changing from propofol
      to sevoflurane. The apparent zero flow pressure (mean+/-SD) was 22+/-10 mmHg with
      sevoflurane and 30+/-14 mmHg with propofol (P<0.01). There was incomplete drug
      crossover due to the limited duration of carotid clamping. CONCLUSIONS: Compared
      with sevoflurane, ipsilateral ICAP and apparent zero flow pressure are both
      higher with propofol. Vasodilatation associated with sevoflurane can cause
      cerebral steal.

PMID- 17197846
TI  - Family-centered preparation for surgery improves perioperative outcomes in
      children: a randomized controlled trial.
AB  - BACKGROUND: Children and parents experience significant anxiety and distress
      during the preoperative period. Currently available interventions are having
      limited efficacy. Based on an integration of the literature in both the
      anesthesia and psychological milieus, the authors developed a behaviorally
      oriented perioperative preparation program for children undergoing surgery that
      targets the family as a whole. METHODS: Children and their parents (n = 408) were
      randomly assigned to one of four groups: (1) control: received standard of care;
      (2) parental presence: received standard parental presence during induction of
      anesthesia; (3) ADVANCE: received family-centered behavioral preparation; and (4)
      oral midazolam. The authors assessed the effect of group assignment on
      preoperative anxiety levels and postoperative outcomes such as analgesic
      consumption and emergence delirium. RESULTS: Parents and children in the ADVANCE
      group exhibited significantly lower anxiety in the holding area as compared with
      all three other groups (34.4+/-16 vs. 39.7+/-15; P=0.007) and were less anxious
      during induction of anesthesia as compared with the control and parental presence
      groups (44.9+/-22 vs. 51.6+/-25 and 53.6+/-25, respectively; P=0.006). Anxiety
      and compliance during induction of anesthesia was similar for children in both
      the ADVANCE and midazolam groups (44.9+/-22 vs. 42.9+/-24; P=0.904). Children in
      the ADVANCE group exhibited a lower incidence of emergence delirium after surgery
      (P=0.038), required significantly less analgesia in the recovery room (P=0.016),
      and were discharged from the recovery room earlier (P=0.04) as compared with
      children in the three other groups. CONCLUSION: The family-centered preoperative
      ADVANCE preparation program is effective in the reduction of preoperative anxiety
      and improvement in postoperative outcomes.

PMID- 17197847
TI  - Influence of "liberal" versus "restrictive" intraoperative fluid administration
      on elimination of a postoperative fluid load.
AB  - BACKGROUND: Previously, the authors found "liberal" fluid administration
      (approximately 3 l Ringer's lactate [RL]) to improve early rehabilitation after
      laparoscopic cholecystectomy, suggesting functional hypovolemia to be present in
      patients receiving "restrictive" fluid administration (approximately 1 l RL).
      Because volume kinetic analysis after a volume load may distinguish between
      hypovolemic versus normovolemic states, the authors applied volume kinetic
      analysis after laparoscopic cholecystectomy to explain the difference in outcome
      between 3 and 1 l RL. METHODS: In a prospective, nonrandomized trial, the authors
      studied 20 patients undergoing laparoscopic cholecystectomy. Ten patients
      received 15 ml/kg RL (group 1) and 10 patients received 40 ml/kg RL (group 2)
      intraoperatively. All other aspects of perioperative management were
      standardized. A 12.5-ml/kg RL volume load was infused preoperatively and 4 h
      postoperatively. The distribution and elimination of the fluid load was estimated
      using volume kinetic analysis. RESULTS: Patient baseline demographics and
      intraoperative data did not differ between groups, except for intraoperative RL,
      having a median of 1,118 ml (range, 900-1,400 ml) in group 1 compared with a
      median of 2,960 ml (range, 2,000-3,960 ml) in group 2 (P<0.01). There were no
      significant preoperative versus postoperative differences in the size of the body
      fluid space expanded by infused fluid (V), whereas the clearance constant kr was
      higher postoperatively versus preoperatively (P=0.03). The preoperative versus
      postoperative changes in volume kinetics including V were not different between
      the two groups. CONCLUSIONS: Elimination of an intravenous fluid load was
      increased after laparoscopic cholecystectomy per se but not influenced by the
      amount of intraoperative fluid administration.

PMID- 17197848
TI  - Effect of a 0.5% dilution of propofol on pain on injection during induction of
      anesthesia in children.
AB  - BACKGROUND: Pain on injection of propofol in children has been reported to be as
      high as 30-80%. The reason for the pain is assumed to be the aqueous phase of the
      propofol emulsion. Therefore, for the first time, this study tested the
      hypothesis that dilution of propofol to a 0.5% emulsion might reduce the
      incidence of pain during propofol injection. METHODS: The study design was
      prospective, monocenter, double-blind, and randomized. Sixty-four children aged 2
      6 yr were scheduled to receive 0.5% or 1.0% propofol in a medium-chain
      triglyceride/long-chain-triglyceride emulsion. Incidence and intensity of pain
      were assessed by spontaneous expressions of pain and withdrawal of the arm. In a
      subgroup of 21 children, serum triglyceride levels were measured before and 3 and
      20 min after induction. Adverse events were recorded. RESULTS: Amounts of
      propofol required until loss of eyelash reflex were 4.40+/-1.01 mg/kg for 0.5%
      propofol and 4.31+/-0.86 mg/kg for 1.0% propofol. Percentages of children who
      showed at least one pain reaction were 23.3% in the 0.5% propofol group and 70.0%
      in the 1.0% propofol group (P<0.001). Serum triglycerides were higher in the 0.5%
      propofol group 3 and 20 min after injection (251.7 vs. 148.8 mg/dl; P=0.001 and
      135.5 vs. 75.5 mg/dl; P=0.03). Adverse events or complications did not occur.
      CONCLUSIONS: Dilution of propofol to a 0.5% medium-chain-triglyceride/long-chain
      triglyceride emulsion reduced pain effectively during injection in children aged
      2-6 yr. Cumulative doses until 4-5 mg/kg propofol led to moderate increases of
      triglyceride levels and did not result in significant adverse events.

PMID- 17197849
TI  - Influence of different strategies of volume replacement on the activity of matrix
      metalloproteinases: an in vitro and in vivo study.
AB  - BACKGROUND: Excessive production of matrix metalloproteinase 9 (MMP-9) is linked
      to tissue damage and anastomotic leakage after large bowel surgery. Hence, the
      aim of this study was to verify whether different strategies of fluids
      administration can reduce MMP-9 expression. METHODS: In the in vitro experiment,
      the authors tested the hypothesis of a direct inhibition of MMP-9 by the fluids
      used perioperatively, i.e., lactated Ringer's solution, 3.4% poligeline, and
      hydroxyethyl starch 130/0.4. In the in vivo experiment, 36 patients undergoing
      surgery for colon cancer were randomly assigned to three groups to receive
      lactated Ringer's solution, poligeline, or hydroxyethyl starch. MMP-9 and tissue
      inhibitor of metalloproteinases were measured from venous blood samples; the MMP
      9/tissue inhibitor of metalloproteinases ratio was calculated as an index of
      equilibrium between the action of MMP-9 and its inhibition. RESULTS: In the in
      vitro experiment, the presence of hydroxyethyl starch 130/0.4 in the MMP-9 assay
      system showed a strong inhibition of the enzymatic activity compared with
      lactated Ringer's solution. In the in vivo experiment, MMP-9 and tissue inhibitor
      of metalloproteinases plasma levels did not differ among the three groups at
      baseline, whereas those levels increased significantly at the end of surgery. At
      that time, the MMP-9 plasma levels and the MMP-9/tissue inhibitor of
      metalloproteinases ratio were significantly higher in the lactated Ringer's
      solution and poligeline groups than in the hydroxyethyl starch group. These
      results were confirmed 72 h after surgery. CONCLUSIONS: This study demonstrates
      that hydroxyethyl starch 130/04 decreases the circulating levels of MMP-9 in
      patients undergoing abdominal surgery.

PMID- 17197850
TI  - Isoflurane provides long-term protection against focal cerebral ischemia in the
      rat.
AB  - BACKGROUND: Long-term neuroprotection by isoflurane has been questioned. The
      authors examined factors in experimental models potentially critical to
      definition of enduring isoflurane neuroprotection. METHODS: Rats were prepared
      for temporary middle cerebral artery occlusion (MCAO). Pericranial normothermia
      was maintained. Neurologic deficits (range, 0-48; 0=no deficit) and cerebral
      infarct volumes were measured. In experiment 1, rats underwent 50 or 80 min MCAO
      while awake or anesthetized with 1.8% isoflurane. Blood pressure was controlled
      with phenylephrine. Outcome was evaluated 2 weeks later. In experiment 2, rats
      underwent 50 min MCAO while awake or anesthetized with isoflurane, with outcome
      evaluated 8 weeks later. In experiment 3, rats underwent 50 min MCAO while awake
      or anesthetized with isoflurane and 2 weeks recovery. Effects of phenylephrine
      and the mitochondrial adenosine triphosphate-sensitive K channel antagonist 5
      hydroxydecanoate were studied. In experiment 4, isoflurane-anesthetized rats
      underwent 50 min MCAO with permanent or temporary common carotid artery
      occlusion, with outcome evaluated 2 weeks later. RESULTS: In experiment 1,
      isoflurane reduced neurologic deficit (median+/-interquartile range; awake vs.
      isoflurane: 11+/-12 vs. 8+/-6 for 80 min and 13+/-4 vs. 3+/-9 for 50 min;
      P=0.0006) and infarct size (160+/-97 vs. 84+/-62 mm for 80 min and 169+/-78 vs.
      68+/-61 mm for 50 min; P<0.0001). In experiment 2, isoflurane protection
      persisted at 8 weeks after ischemia. In experiment 3, there was no effect of
      phenylephrine or 5-hydroxydecanoate. In experiment 4, permanent common carotid
      ligation increased infarct size threefold versus temporary occlusion.
      CONCLUSIONS: Isoflurane repeatedly improved long-term neurologic and histologic
      outcome from focal ischemia independent of ischemia duration, perfusion pressure,
      or pretreatment with 5-hydroxydecanoate.

PMID- 17197851
TI  - Milrinone combined with vasopressin improves cardiac index after cardiopulmonary
      resuscitation in a pig model of myocardial infarction.
AB  - BACKGROUND: Milrinone used for acute cardiac insufficiency could be of interest
      during cardiopulmonary resuscitation because of its positive inotropic effects.
      In this study, the combination of milrinone-vasopressin was compared with
      epinephrine and vasopressin, as well as with the combination of epinephrine
      vasopressin, in reference to hemodynamics. METHODS: Thirty-two pigs underwent
      ligation of the circumflex coronary artery and induction of ventricular
      fibrillation lasting for 4 min. Cardiopulmonary resuscitation was performed after
      randomization to one of four groups: epinephrine (30-microg/kg bolus),
      vasopressin (0.4-U/kg bolus), epinephrine-vasopressin (15-microg/kg epinephrine
      bolus, 0.2-U/kg vasopressin bolus), or milrinone-vasopressin (0.4-U/kg
      vasopressin bolus, 50-microg/kg milrinone bolus over 5 min and a continuous
      infusion of 0.4 microg.kg.min). The hemodynamic variables were measured before
      cardiopulmonary resuscitation as well as 4, 8, 15, and 30 min after return of
      spontaneous circulation. RESULTS: All animals were resuscitated successfully. The
      animals of the milrinone-vasopressin group displayed significantly (P<0.05)
      higher cardiac index values (30 min after return of spontaneous circulation:
      epinephrine, 65.8+/-13.2; vasopressin, 70.7+/-18.3; epinephrine-vasopressin,
      69.1+/-36.2; milrinone-vasopressin, 120.7+/-34.8 ml.min.kg) without a decrease in
      mean arterial pressure or coronary perfusion pressure. CONCLUSIONS: The
      combination of vasopressin-milrinone as compared with epinephrine during
      cardiopulmonary resuscitation leads to an improved cardiac index without relevant
      decrease of mean arterial pressure or coronary perfusion pressure.

PMID- 17197852
TI  - Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar
      concentration, learning, and the righting reflex in mice engineered to express
      alpha1 gamma-aminobutyric acid type A receptors unresponsive to isoflurane.
AB  - BACKGROUND: Enhancement of the function of gamma-aminobutyric acid type A
      receptors containing the alpha1 subunit may underlie a portion of inhaled
      anesthetic action. To test this, the authors created gene knock-in mice harboring
      mutations that render the receptors insensitive to isoflurane while preserving
      sensitivity to halothane. METHODS: The authors recorded miniature inhibitory
      synaptic currents in hippocampal neurons from hippocampal slices from knock-in
      and wild-type mice. They also determined the minimum alveolar concentration
      (MAC), and the concentration at which 50% of animals lost their righting reflexes
      and which suppressed pavlovian fear conditioning to tone and context in both
      genotypes. RESULTS: Miniature inhibitory postsynaptic currents decayed more
      rapidly in interneurons and CA1 pyramidal cells from the knock-in mice compared
      with wild-type animals. Isoflurane (0.5-1 MAC) prolonged the decay phase of
      miniature inhibitory postsynaptic currents in neurons of the wild-type mice, but
      this effect was significantly reduced in neurons from knock-in mice. Halothane (1
      MAC) slowed the decay of miniature inhibitory postsynaptic current in both
      genotypes. The homozygous knock-in mice were more resistant than wild-type
      controls to loss of righting reflexes induced by isoflurane and enflurane, but
      not to halothane. The MAC for isoflurane, desflurane, and halothane did not
      differ between knock-in and wild-type mice. The knock-in mice and wild-type mice
      did not differ in their sensitivity to isoflurane for fear conditioning.
      CONCLUSIONS: gamma-Aminobutyric acid type A receptors containing the alpha1
      subunit participate in the inhibition of the righting reflexes by isoflurane and
      enflurane. They are not, however, involved in the amnestic effect of isoflurane
      or immobilizing actions of inhaled agents.

PMID- 17197853
TI  - Determination of the EC50 amnesic concentration of etomidate and its diffusion
      profile in brain tissue: implications for in vitro studies.
AB  - BACKGROUND: Etomidate is a widely used general anesthetic that has become a
      useful tool to investigate mechanisms of anesthetic action in vivo and in brain
      slices. However, the free aqueous concentration of etomidate that corresponds to
      amnesia in vivo and the diffusion profile of etomidate in brain slices are not
      known. METHODS: The authors assessed the effect of intraperitoneally injected
      etomidate on contextual fear conditioning in mice. Etomidate concentrations in
      brain tissue were obtained by high-performance liquid chromatography. Uptake
      studies in 400-microm-thick brain slices were used to calculate the diffusion and
      partition coefficients of etomidate. A diffusion model was used to calculate the
      expected concentration profile within a brain slice as a function of time and
      depth. The predicted rate of drug equilibration was compared with the onset of
      electrophysiologic effects on inhibitory circuit function in recordings from
      hippocampal brain slices. RESULTS: Etomidate impaired contextual fear
      conditioning with an ED50 dose of 11.0+/-0.1 mg after intraperitoneal injection,
      which corresponded to an EC50 brain concentration of 208+/-9 ng/g. The
      brain:artificial cerebrospinal fluid partition coefficient was 3.35, yielding an
      EC50,amnesia aqueous concentration of 0.25 microm. The diffusion coefficient was
      approximately 0.2x10 cm/s. The development of etomidate action in hippocampal
      brain slices was compatible with the concentration profile predicted by this
      diffusion coefficient. CONCLUSIONS: The free aqueous concentration of etomidate
      corresponding to amnesia, as defined by impaired contextual fear conditioning in
      mice, is 0.25 microM. Diffusion of etomidate into brain slices requires
      approximately an hour to reach 80% equilibration at a typical recording depth of
      100 microm. This information will be useful in designing and interpreting in
      vitro studies using etomidate.

PMID- 17197854
TI  - Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary
      hypertension in a rat model of congestive heart failure.
AB  - BACKGROUND: Most patients with congestive heart failure (CHF) develop pulmonary
      venous hypertension, but right ventricular afterload is frequently further
      elevated by increased pulmonary vascular resistance. To investigate whether
      inhalation of a vasodilatory phosphodiesterase-3 inhibitor may reverse this
      potentially detrimental process, the authors studied the effects of inhaled or
      intravenous milrinone on pulmonary and systemic hemodynamics in a rat model of
      CHF. METHODS: In male Sprague-Dawley rats, CHF was induced by supracoronary
      aortic banding, whereas sham-operated rats served as controls. Milrinone was
      administered as an intravenous infusion (0.2-1 microg.kg body weight.min) or by
      inhalation (0.2-5 mg/ml), and effects on pulmonary and systemic hemodynamics and
      lung water content were measured. RESULTS: In CHF rats, intravenous infusion of
      milrinone reduced both pulmonary and systemic arterial blood pressure. In
      contrast, inhalation of milrinone predominantly dilated pulmonary blood vessels,
      resulting in a reduced pulmonary-to-systemic vascular resistance ratio. Repeated
      milrinone inhalations in 20-min intervals caused a stable reduction of pulmonary
      artery pressure. No hemodynamic effects were detected when 0.9% NaCl was
      administered instead of milrinone or when milrinone was inhaled in sham-operated
      rats. No indications of potentially adverse effects of milrinone inhalation in
      CHF, such as left ventricular volume overload, were detected. Moreover, lung
      edema was significantly reduced by repeated milrinone inhalation. CONCLUSION: If
      these results can be confirmed in humans, inhalation of nebulized milrinone may
      present a novel, effective, safe, and pulmonary selective strategy for the
      treatment of pulmonary venous hypertension in CHF.

PMID- 17197855
TI  - Novel starches: single-dose pharmacokinetics and effects on blood coagulation.
AB  - BACKGROUND: Carboxymethyl starch (CMS) and carboxymethylated hydroxyethyl starch
      (CM-HES) might offer advantages over hydroxyethyl starch (HES) with regard to
      their volume expansion effect and their pharmacokinetic characteristics. The goal
      of the current study was to determine the pharmacokinetics of CMS and CM-HES and
      to investigate their influence on blood coagulation in comparison with the
      standard low-molecular, low-substituted HES (130/0.42) used in Europe. METHODS:
      The study was conducted as a randomized, blinded, parallel three-group study in
      30 pigs. Twenty ml/kg of 6% HES (control), 6% CMS, or 6% CM-HES was infused as a
      single dose, and serial blood sampling was performed over 20 h to measure plasma
      concentration and molecular weight and to assess blood coagulation. Concentration
      effect relations were assessed by pharmacokinetic-pharmacodynamic analysis.
      RESULTS: CMS and CM-HES showed significantly higher plasma concentrations and
      molecular weights over 20 h (P for both<0.001) with smaller volumes of
      distribution and longer elimination rates during the terminal phase (P for
      both<0.01) when compared with HES. CMS and CM-HES impaired whole blood
      coagulation more than HES as assessed by Thrombelastograph analysis (Haemoscope
      Corporation, Niles, IL). However, similar effects of all three starch
      preparations on blood coagulation were found when related to the plasma
      concentrations in mass units. CONCLUSIONS: Carboxymethylation of starch results
      in an increased intravascular persistence and a slower fragmentation compared
      with HES. The greater impairment of blood coagulation by CMS and CM-HES seems to
      be caused by the higher plasma concentrations.

PMID- 17197856
TI  - Sevoflurane breakdown produces flammable concentrations of hydrogen.
AB  - BACKGROUND: Fires, explosions, and extreme heat production may occur when
      sevoflurane reacts with desiccated barium hydroxide lime. The identity of the
      flammable gas has not previously been published, although carbon monoxide,
      methanol, formaldehyde, and methyl formate have been identified in low
      quantities. METHODS: The authors reacted sevoflurane with excess desiccated
      barium hydroxide lime or soda lime at 55 degrees, 100 degrees, 200 degrees, 300
      degrees, and 400 degrees C. Formaldehyde, methanol, sodium formate, and
      hexafluoroisopropanol were reacted with barium hydroxide lime at 300 degrees or
      400 degrees C. The authors measured hydrogen production by gas chromatography
      with a thermal conductivity detector and calculated the molar yield of hydrogen
      produced. RESULTS: Up to 3 moles of hydrogen were produced per mole of
      sevoflurane degraded. Each mole of formaldehyde produced up to 2 moles of
      hydrogen at 400 degrees C. Formate and hexafluoroisopropanol produced up to 1
      mole of hydrogen each at 400 degrees C. More than 2 moles of hydrogen were
      produced by methanol at 400 degrees C. Soda lime and barium hydroxide lime
      produced similar amounts of hydrogen from sevoflurane above 200 degrees C, but
      barium hydroxide lime produced more than soda lime at lower temperatures. The
      temperature above which large amounts of hydrogen were produced seemed to be 300
      degrees C. CONCLUSIONS: Up to 3 moles of hydrogen are produced by the chemical
      reaction of sevoflurane with heated, desiccated absorbent. The high yield, ease
      of ignition, and low tissue solubility of hydrogen make it the most likely fuel
      in anesthesia machine fires due to the reaction of sevoflurane with desiccated
      absorbent.

PMID- 17197857
TI  - Determination of the full dose-response relation of intrathecal bupivacaine,
      levobupivacaine, and ropivacaine, combined with sufentanil, for labor analgesia.
AB  - BACKGROUND: Ropivacaine and levobupivacaine are local anesthetics that produce
      less motor block and greater sensory-motor separation when compared with equal
      milligram doses of bupivacaine. Although minimum local analgesic concentration
      studies suggested that they are less potent than bupivacaine, full dose-response
      studies have not been performed. The current trial describes the dose-response
      relation of levobupivacaine, ropivacaine, and bupivacaine, combined with
      sufentanil, when used for intrathecal labor analgesia. METHODS: Four hundred
      fifty term parturients in active labor were included in this double-blind,
      randomized trial. Combined spinal-epidural anesthesia was performed, and
      ropivacaine, levobupivacaine, or bupivacaine was intrathecally administered in a
      dose of 1.0, 1.5, 2.0, 2.5, 3.0, or 3.5 mg, always combined with 1.5 microg
      sufentanil. Patients were considered responders to spinal analgesia if the visual
      analog scale score for pain was less than 25 mm within 15 min and the visual
      analog scale score remained less than 25 mm for 45 min. Patient demographics,
      obstetric data, maternal side effects, and fetal and neonatal well-being were
      noted. Group-specific dose-response curves were constructed using a probit
      regression model. RESULTS: The ED95 of bupivacaine was 3.3 mg (95% confidence
      interval, 2.9-4.1). The ED95s of ropivacaine and levobupivacaine were 4.8 mg (95%
      confidence interval, 4.0-6.7) and 5.0 mg (95% confidence interval, 4.1-7.0),
      respectively. Racemic bupivacaine was significantly more potent than ropivacaine
      (P=0.0027) and levobupivacaine (P=0.0006). Ropivacaine and levobupivacaine were
      of similar potency (P=0.91). CONCLUSIONS: This full dose-response study suggests
      that ropivacaine and levobupivacaine are of similar potency, whereas bupivacaine
      is more potent than both other drugs.

PMID- 17197858
TI  - Automated documentation error detection and notification improves anesthesia
      billing performance.
AB  - BACKGROUND: Documentation of key times and events is required to obtain
      reimbursement for anesthesia services. The authors installed an information
      management system to improve record keeping and billing performance but found
      that a significant number of their records still could not be billed in a timely
      manner, and some records were never billed at all because they contained
      documentation errors. METHODS: Computer software was developed that automatically
      examines electronic anesthetic records and alerts clinicians to documentation
      errors by alphanumeric page and e-mail. The software's efficacy was determined
      retrospectively by comparing billing performance before and after its
      implementation. Staff satisfaction with the software was assessed by survey.
      RESULTS: After implementation of this software, the percentage of anesthetic
      records that could never be billed declined from 1.31% to 0.04%, and the median
      time to correct documentation errors decreased from 33 days to 3 days. The
      average time to release an anesthetic record to the billing service decreased
      from 3.0+/-0.1 days to 1.1+/-0.2 days. More than 90% of staff found the system to
      be helpful and easier to use than the previous manual process for error detection
      and notification. CONCLUSION: This system allowed the authors to reduce the
      median time to correct documentation errors and the number of anesthetic records
      that were never billed by at least an order of magnitude. The authors estimate
      that these improvements increased their department's revenue by approximately
      $400,000 per year.

PMID- 17197859
TI  - Diagnosis and treatment of vascular air embolism.
AB  - Vascular air embolism is a potentially life-threatening event that is now
      encountered routinely in the operating room and other patient care areas. The
      circumstances under which physicians and nurses may encounter air embolism are no
      longer limited to neurosurgical procedures conducted in the "sitting position"
      and occur in such diverse areas as the interventional radiology suite or
      laparoscopic surgical center. Advances in monitoring devices coupled with an
      understanding of the pathophysiology of vascular air embolism will enable the
      physician to successfully manage these potentially challenging clinical
      scenarios. A comprehensive review of the etiology and diagnosis of vascular air
      embolism, including approaches to prevention and management based on experimental
      and clinical data, is presented. This compendium of information will permit the
      healthcare professional to rapidly assess the relative risk of vascular air
      embolism and implement monitoring and treatment strategies appropriate for the
      planned invasive procedure.

PMID- 17197860
TI  - The Unitarian Service Committee medical mission: contribution by the United
      States to Post-World War II Japanese anesthesiology.

PMID- 17197861
TI  - An early example of evidence-based medicine: hypoxemia due to nitrous oxide.
AB  - Diffusion anoxia. By Bernard Raymond Fink. Anesthesiology 1955; 16:511-14. In
      1955, Dr. Bernard Raymond Fink published his findings that described the
      mechanism by which hypoxemia occurred when nitrous oxide-oxygen anesthesia was
      discontinued and room air breathing commenced. Using an ear oximeter and brachial
      artery blood gases, he measured oxygen saturation in eight healthy patients who
      had received 75% nitrous oxide-25% oxygen for gynecologic surgery. He showed that
      oxygen saturation decreased from 5% to 10% and often reached a value below 90%
      when the patient began room air breathing after the nitrous oxide-oxygen was
      discontinued. The effect was seen over a 10-min period. He concluded that "anoxia
      arises because the outward diffusion of nitrous oxide lowers the alveolar partial
      pressure of oxygen." This phenomenon can become a causative factor of cardiac
      arrest in patients with impaired pulmonary or cardiac reserves.

PMID- 17197862
TI  - Coiling of stimulating perineural catheters.

PMID- 17197863
TI  - Ultrasound-guided perineural catheters have already arrived.

PMID- 17197865
TI  - Perineural infusion of local anesthetics: "more to the review".

PMID- 17197866
TI  - Safety of parecoxib and valdecoxib after noncardiac surgery: lack of
      demonstration.

PMID- 17197868
TI  - Ultrasound guidance for peripheral venous access: a simplified seldinger
      technique.

PMID- 17197874
TI  - Preexposure prophylaxis for HIV infection: it's not as easy as ABC.

PMID- 17197875
TI  - HIV and malaria: interactions and implications.
AB  - PURPOSE OF REVIEW: This review summarizes accumulating evidence of interactions
      between HIV and malaria and implications related to prevention and treatment of
      coinfection. RECENT FINDINGS: HIV-infected persons are at increased risk for
      clinical malaria; the risk is greatest when immune suppression is advanced.
      Adults with advanced HIV may be at risk for failure of malaria treatment,
      especially with sulfa-based therapies. Malaria is associated with increases in
      HIV viral load that, while modest, may impact HIV progression or the risk of HIV
      transmission. Cotrimoxazole prophylaxis greatly reduces the risk of malaria in
      people with HIV; the risk can be further reduced with antiretroviral treatment
      and the use of insecticide treated mosquito nets. Increased numbers of doses of
      intermittent preventive treatment during pregnancy can reduce the risk of
      placental malaria in women with HIV. SUMMARY: Interactions between malaria and
      HIV have important public health implications. People with HIV should use
      cotrimoxazole and insecticide treated mosquito nets. Malaria prevention is
      particularly important for pregnant women with HIV, although more information is
      needed about the best combination of strategies for prevention. In people with
      HIV, malaria diagnoses should be confirmed, highly effective drugs should be used
      for treatment, and possible drug interactions should be considered.

PMID- 17197876
TI  - HIV and pneumococcal disease.
AB  - PURPOSE OF REVIEW: To describe the impact of highly active antiretroviral therapy
      on the burden of pneumococcal disease and advances in our understanding of the
      impact of HIV on this disease. RECENT FINDINGS: Although highly active
      antiretroviral therapy has reduced the burden of pneumococcal disease among HIV
      infected adults, these infections remain far more common than in HIV uninfected
      adults. HIV-infected adults who smoke or have comorbidities are at particular
      risk. In the absence of highly active antiretroviral therapy, pneumococcal
      meningitis has emerged in Africa as a major disease burden with a high mortality
      among HIV-infected children and adults. Conjugate pneumococcal vaccine protects
      HIV-infected infants from pneumococcal pneumonia. In the United States, where
      conjugate vaccine is given to children, herd immunity has reduced the burden of
      invasive pneumococcal disease among HIV-infected adults. SUMMARY: The
      pneumococcus remains a significant cause of morbidity and mortality among HIV
      infected children and adults, both in developed and in developing countries.

PMID- 17197877
TI  - The management of HIV and hepatitis B coinfection.
AB  - PURPOSE OF REVIEW: Coinfection with HIV and hepatitis B virus has a significant
      impact on the natural history of hepatitis B disease with faster rates of
      progression to cirrhosis and end stage liver disease. An increasing number of
      hepatitis B virus active drugs are now available, many of which have dual anti
      HIV activity. This review highlights the most important recent developments in
      the management of HIV and hepatitis B virus coinfection. RECENT FINDINGS: Natural
      history studies continue to confirm the increased rate of liver-related mortality
      in coinfected individuals and the importance of hepatocellular carcinoma in this
      population. The most recent studies of adefovir and tenofovir in open label use
      in coinfected individuals are discussed and new data on the activity of
      emtricitabine, entecavir and pegylated interferon are presented. Strategies for
      use of these new options for anti-hepatitis B virus therapy in coinfected
      individuals are discussed. SUMMARY: Prevention of end stage liver disease and
      hepatocellular carcinoma in the coinfected population is vital and the increasing
      availability of drugs with potent anti-hepatitis B activity is encouraging.
      Appropriate diagnosis and monitoring of hepatitis B, coupled with better
      understanding of the mechanisms of drug resistance, will enable clinicians to
      manage coinfection more effectively.

PMID- 17197878
TI  - Epidemiology of antiretroviral drug resistance in drug-naive persons.
AB  - PURPOSE OF REVIEW: An update is given on the epidemiology of transmitted
      antiretroviral drug resistance among HIV-1-infected adults. RECENT FINDINGS:
      Reported prevalence surveys show inter-region and intra-region variability, in
      part as a result of methodological differences. Temporal trends are difficult to
      define as rates appear stable or declining in some cohorts but increasing in
      others. While the highest prevalence continues to be observed in North America,
      Western Europe and areas of South America, transmitted antiretroviral drug
      resistance is emerging in countries where access to therapy is being scaled up,
      including regions of sub-Saharan Africa. Resistance patterns in drug-experienced
      and drug-naive persons, transmission efficiency of resistant variants and their
      ability to persist as dominant species in the absence of drug pressure determine
      the prevalence of resistance mutations in persons with transmitted antiretroviral
      drug resistance. The most frequently detected mutations are in reverse
      transcriptase, especially thymidine analogue mutations, whereas protease
      mutations other than natural polymorphisms are generally less prevalent. SUMMARY:
      A consensus is required internationally on how transmitted antiretroviral drug
      resistance should be investigated and reported. Although routine testing methods
      provide only minimal estimates of the prevalence of transmitted antiretroviral
      drug resistance, successful treatment outcomes are observed in patients with
      resistance receiving first-line therapy guided by baseline resistance testing.

PMID- 17197879
TI  - Circumcision and HIV transmission.
AB  - PURPOSE OF REVIEW: To review the recent literature on male circumcision and its
      effect on HIV acquisition. RECENT FINDINGS: The report from the randomized
      clinical trial of male circumcision in South Africa demonstrating a 60%
      protective effect in preventing HIV acquisition provided the first clinical trial
      evidence of efficacy of male circumcision in protecting men against HIV
      infection. This protective effect was consistent with both ecological and
      epidemiologic studies which also show a protective effect of 50-70% in men at
      high risk for HIV infection. Biological studies also demonstrate an increased
      number of HIV receptor cells in the mucosa of foreskin providing additional
      evidence of HIV susceptibility in the uncircumcised male. Male circumcision may
      also have a beneficial effect in preventing HIV acquisition in women and lowering
      selected sexually transmitted infections in both sexes. SUMMARY: The results of
      two ongoing randomized clinical trials of male circumcision in Kenya and Uganda
      are awaited with interest, however male circumcision should be carefully
      considered as a potential public health tool in preventing HIV acquisition. If
      other trials confirm the results of the South African trial, implementation of
      this surgical procedure will need to be carefully scaled up and integrated into
      other prevention programs with emphasis on surgical training, aseptic techniques,
      acceptability, availability and cultural considerations.

PMID- 17197880
TI  - Postexposure prophylaxis after sexual exposure to HIV.
AB  - PURPOSE OF REVIEW: HIV postexposure prophylaxis is often recommended following
      potential sexual exposure to HIV. Recent data address the effectiveness of
      postexposure prophylaxis and prevention counseling, cost-effectiveness,
      antiretroviral options, challenges with nonoccupational postexposure prophylaxis
      among adolescents and children and following sexual assault in high HIV
      prevalence areas, and a successful program in Amsterdam. RECENT FINDINGS:
      Postexposure prophylaxis is not completely protective. Seroconversion may result
      from antiretroviral failure or from ongoing exposures. Postexposure prophylaxis
      associated risk reduction counseling results in reductions in subsequent risk
      behavior. Programs that target outreach and limit prescriptions to those with
      exposure sources who are at risk of being HIV infected are cost-effective. Less
      restrictive guidelines result in more prescriptions for low-risk exposures; this
      practice is not cost-effective. The ideal antiretrovirals for postexposure
      prophylaxis use have not been established. Tenofovir has several attractive
      properties. Developing systems to support the effective delivery of postexposure
      prophylaxis among children and adolescents and following sexual assault in high
      HIV prevalence, resource limited settings is challenging. SUMMARY: Numerous
      national and international guidelines recommend postexposure prophylaxis
      following potential sexual exposure to HIV. Maximizing adherence and minimizing
      subsequent HIV exposures will be critical to enhancing the effectiveness of this
      HIV prevention intervention.

PMID- 17197881
TI  - The criminalization of HIV transmission in England and Wales: a brief review of
      the issues arising.
AB  - PURPOSE OF REVIEW: The HIV virus has been present in our society for more than
      two decades. Although there was originally much academic interest in the
      possibility of prosecuting for the reckless transmission of HIV in England and
      Wales, it was thought impossible by many (including the government) under
      existing legislation. The first prosecution in England in 2003 (following the
      first UK prosecution in 2001, in Scotland) provoked a great deal of surprise not
      least in the HIV voluntary sector, which has since been campaigning for the
      cessation of such prosecutions. This review examines the law in this area and
      provides an understanding of the development of the ethical and other issues
      involved. RECENT FINDINGS: Since 2003 there have been seven further convictions
      for the reckless transmission of HIV in England and Wales. These prosecutions
      have led to several responses that are discussed here and the current
      developments in this area outlined. SUMMARY: Whether it is right to prosecute the
      reckless transmission of HIV remains a controversial, pressing question. This
      brief article aims to dissect and question the relevant issues and help inform
      this debate.

PMID- 17197882
TI  - The resurgence of syphilis among men who have sex with men.
AB  - PURPOSE OF REVIEW: To identify recent progress and emerging problems in
      addressing syphilis among men who have sex with men. RECENT FINDINGS: A
      resurgence of syphilis has occurred among men who have sex with men in many
      developed countries. Infection has been associated with HIV coinfection, multiple
      partners, and recreational drug use. Unlike HIV, oral sex appears to be a common
      route of syphilis transmission. Many prevention approaches have shown, at best,
      modest success. Variable clinical presentation and potentially inconclusive lab
      tests make diagnosis confusing. SUMMARY: As the infection remains relatively
      rare, clinicians treating men who have sex with men should maintain a high index
      of suspicion for syphilis lesions, and should screen their sexually active
      patients for latent disease. Debates about syphilis control and treatment
      continue. The clinical manifestations, serologic responses, efficacy of
      treatment, and complications of syphilis have always been complicated. HIV
      coinfection adds to the confusion.

PMID- 17197883
TI  - Risk selection and targeted interventions in community-based control of
      chlamydia.
AB  - PURPOSE OF REVIEW: To describe recent developments in the community-based
      approach of high-risk groups for Chlamydia trachomatis infection, and to discuss
      the assessment of impact of selective systematic screening on the transmission of
      C. trachomatis in the community. RECENT FINDINGS: Two large home-based screening
      programs in Europe have recently shown that systematic postal screening for C.
      trachomatis infection is feasible, but certain high-risk groups are poor
      participators. This underscores the need for risk selection and targeted
      approaches. A prediction rule has been developed which can assist in identifying
      high-risk groups and can be used as a tool for (self) selection for screening.
      The Internet has been shown to be a promising medium to promote chlamydia
      testing. School-based programs also succeed in including high-risk groups in
      screening programs. Recently developed dynamic simulation models, which take into
      account transmission of C. trachomatis, can assist in the development and
      evaluation of targeted screening strategies. SUMMARY: Chlamydia will not likely
      be controlled by one standard approach. Risk selection strategies need further
      development and different systematic approaches at the community level, including
      postal screening, school-based screening, and the Internet may produce the
      desired public health effect of decreasing morbidity and reducing the
      transmission of C. trachomatis in the community.

PMID- 17197884
TI  - Male circumcision as a preventive measure against HIV and other sexually
      transmitted diseases.
AB  - PURPOSE OF REVIEW: In 2005, 4.1 million people were infected with HIV. There is
      an urgent need to intensify and expand HIV prevention methods. Male circumcision
      is one of several potential approaches. This review summarizes recent evidence
      for the potential of male circumcision to prevent HIV and other sexually
      transmitted infections. RECENT FINDINGS: The first randomized controlled trial of
      adult male circumcision found a highly significant 60% reduction in HIV incidence
      among men in the intervention arm. Modelling this effect predicts that widespread
      implementation of male circumcision could avert 2 million HIV infections over the
      next decade in sub-Saharan Africa. The biological rationale is that the foreskin
      increases risk of HIV infection due to the high density of HIV target cells and
      lack of keratinization of the inner mucosal surface. SUMMARY: There is strong
      evidence that male circumcision reduces risk of HIV, syphilis and chancroid. If
      results are confirmed by two ongoing trials in sub-Saharan Africa, provision of
      safe male circumcision could be added to HIV prevention packages in high
      incidence settings. This would also provide an opportunity for HIV-prevention
      education and counselling to young men at high risk of infection.

PMID- 17197885
TI  - Consequences of herpes simplex virus in pregnancy and their prevention.
AB  - PURPOSE OF REVIEW: New findings reveal that first-time infection of the mother is
      the most important factor for the transmission of genital herpes from mother to
      fetus/newborn. Interventions based on these findings will lead to new management
      of the pregnant patient with genital herpes prior to pregnancy and measures to
      prevent the acquisition of herpes during pregnancy. RECENT FINDINGS: Risk factors
      for the transmission of herpes from mother to newborn have been detailed. It is
      the pregnant woman who acquires genital herpes as a primary infection in the
      latter half of pregnancy, rather than prior to pregnancy, who is at greatest risk
      of transmitting this virus to her newborn. This is true for both herpes simplex
      virus type-1 and herpes simplex virus type-2. Additional risk factors for
      neonatal herpes simplex virus infection include the use of a fetal-scalp
      electrode and maternal age of less than 21 years. SUMMARY: Risk factors for the
      transmission of herpes from mother to newborn are detailed. Antiviral suppressive
      therapy initiated in the late third trimester has been shown to decrease viral
      shedding and the need for cesarean section.

PMID- 17197886
TI  - Interstitial cystitis pathogenesis and treatment.
AB  - PURPOSE OF REVIEW: Interstitial cystitis remains an idiopathic illness
      characterized by urinary frequency, urgency and pelvic pain with substantial
      morbidity in those affected. There is significant variability in the
      presentation, severity of symptoms and response to therapy. This review focuses
      on recent findings on the possible pathogenesis and potential treatments for this
      disease. RECENT FINDINGS: Interstitial cystitis is manifested by sensory
      hypersensitivity. A small volume of urine will be associated with an exaggerated
      sensation of pain or pressure and urinary urgency. There is continued research
      regarding how this process is initiated and maintained and to what extent
      systemic dysfunction of the immune or autonomic nervous system may play a role.
      The urothelial lining has been demonstrated to be capable of secreting a large
      number of potential signaling molecules that may be significant factors in the
      disease. SUMMARY: The pathogenesis of interstitial cystitis remains uncertain and
      the illness has significant diversity. Additional research is needed to establish
      subtypes that share common processes that can be targeted for treatment as a
      single effective therapy for the condition remains elusive.

PMID- 17197887
TI  - Procalcitonin and pyelonephritis in children.
AB  - PURPOSE OF REVIEW: In the past few years, procalcitonin has been proposed as a
      sensitive and specific inflammatory marker in various fields of medicine,
      especially in infectivology, where it has been used to discriminate between
      bacterial infections, viral infections and inflammation processes. Recently,
      different studies have emerged in the literature on the use of this marker to
      identify renal involvement in febrile urinary tract infections. RECENT FINDINGS:
      Procalcitonin seems to be a valid biological marker, with an acceptable
      sensitivity and specificity, which predicts a renal involvement of the infection
      (pyelonephritis), in comparison with the low specificity of C-reactive protein.
      Procalcitonin also seems to be correlated with the degree of the involvement at
      the moment of diagnosis of febrile urinary tract infections and with scarring.
      SUMMARY: Renal involvement has always been the main diagnostic objective in
      children with febrile urinary tract infections. If more studies confirm the
      correlation between procalcitonin, renal involvement during urinary infections
      and scar formation, we will finally have a noninvasive tool that can identify
      children at risk of complications and in need of a close follow-up as early as
      their first episode of febrile urinary tract infection.

PMID- 17197888
TI  - Bibliography. Current world literature. HIV infection and AIDS.

PMID- 17197889
TI  - Immunohistochemical analysis of sox9 in ovarian Sertoli cell tumors and other
      tumors in the differential diagnosis.
AB  - The distinction of ovarian Sertoli cell tumor from other tumors in the
      histological differential diagnosis, particularly endometrioid carcinoma and
      carcinoid tumor, may be difficult. Many immunohistochemical markers have been
      studied for this differential diagnosis, but currently available markers are
      neither 100% sensitive nor specific. Sox9 is a transcription factor involved in
      Sertoli cell differentiation in the testis. The role that this molecule plays in
      the pathogenesis of ovarian Sertoli cell tumors and the potential use as an
      immunohistochemical marker for differential diagnosis have not been investigated.
      Immunohistochemical staining for Sox9 was performed in 152 ovarian tumors: pure
      Sertoli cell tumor (n = 36), endometrioid borderline tumor (n = 38), well
      differentiated endometrioid carcinoma (n = 26), sertoliform endometrioid
      carcinoma (n = 13), and carcinoid tumor (n = 39). Nuclear expression was
      considered positive. Extent and intensity of staining were semiquantitatively
      scored. In addition, immunohistochemical composite scores in positive cases
      (ranging from 1 to 12) were calculated based on the extent score multiplied by
      the intensity score. Sox9 was expressed in 44% of Sertoli cell tumors, 55% of
      endometrioid borderline tumors, 65% of well-differentiated endometrioid
      carcinomas, 39% of sertoliform endometrioid carcinomas, and 10% of carcinoid
      tumors. The mean Sox9 immunohistochemical composite scores in positive cases were
      6.3 for Sertoli cell tumor, 5.3 for endometrioid borderline tumor, 8.0 for well
      differentiated endometrioid carcinoma, 2.8 for sertoliform endometrioid
      carcinoma, and 6.8 for carcinoid tumor. The differences in the mean Sox9
      composite scores between Sertoli cell tumor and the other tumor categories were
      not statistically significant (p values ranged from 0.092 to 0.523). We conclude
      that Sox9 is variably expressed in ovarian Sertoli cell tumor and other tumors
      that are in the differential diagnosis and, thus, is not helpful for
      immunohistochemical distinction. Understanding the role of Sox9 in the
      pathogenesis of ovarian Sertoli cell tumor requires further study.

PMID- 17197890
TI  - Prostate-derived Ets factor is overexpressed in serous epithelial ovarian tumors.
AB  - The frequent overexpression of prostate-derived Ets factor (PDEF) mRNA in ovarian
      cancer has been previously reported. The aim of this study was to evaluate PDEF
      protein expression in ovarian cancer and how this expression might vary at
      different stages of epithelial ovarian tumors in comparison to normal ovary. A
      new rabbit polyclonal antibody to PDEF was prepared, and immunohistochemistry was
      performed on tissue sections from 12 normal ovaries, 10 cases of benign serous
      cystadenoma, 17 cases of low malignant potential tumor, 19 cases of stage 1, and
      15 cases of advanced stage primary epithelial (serous) ovarian carcinomas and
      their peritoneal metastases. Expression levels were assessed based on the
      percentage of positively staining cells and the intensity of staining. All 12
      normal ovary and 10 benign serous cystadenoma cases were negative for PDEF
      expression. In contrast, 6 of 17 (35%) low malignant potential tumors, 5 of 19
      (27%) stage 1, and 5 of 15 (33%) advanced stage ovarian tumors stained positive
      for PDEF expression. Together, these results show frequent overexpression of PDEF
      protein in epithelial ovarian tumors and its lack of expression in normal ovary
      and cystadenomas, and this supports a role for PDEF in ovarian tumorigenesis.
      Furthermore, these results suggest that PDEF is a potential marker and target in
      ovarian cancer.

PMID- 17197891
TI  - Oxyphilic adenomatoid tumor of the ovary: a case report with discussion of the
      differential diagnosis of ovarian tumors with vacuoles and related spaces.
AB  - We describe an unusual example of ovarian adenomatoid tumor that was an
      incidental finding in the ovary of a 52-year-old woman and was characterized by
      cells with abundant eosinophilic cytoplasm, an occasional feature of the
      adenomatoid tumor but one that, in an ovarian example, may cause added diagnostic
      confusion to that already engendered by the rarity of this neoplasm in the ovary.
      The typical numerous small vacuoles of the neoplasm sometimes had the appearance
      of signet ring cells. These 2 features (oxyphil and signet ring cells) caused a
      broad differential. Tumor cells were positive with broad-spectrum cytokeratins as
      well as mesothelial markers CK5/6, WT1, and calretinin. In reporting this case,
      we focus on the differential diagnosis of ovarian neoplasms and tumorlike
      conditions with vacuoles and related spaces, a topic that embraces many diverse
      entities.

PMID- 17197892
TI  - Primary osteosarcoma of the ovary: a case report and literature review.
AB  - Pure osteosarcomas, in which this tumor is not the mesenchymal component of a
      biphasic tumor, are only rarely encountered in the ovary. Herein, we report a
      case of a pure ovarian osteoarcoma and review all previously reported cases of
      ovarian involvement by osteosarcoma in the English literature. The latter
      includes (with the present case) 6 cases of pure osteosarcoma (Group A), 5 cases
      of osteosarcoma arising from a teratoma (Group B), and 2 cases of osteosarcomas
      of osseous origin (humerus and maxilla) metastatic to the ovary (Group C). The
      average ages of the Groups A, B, and C patients were 52.6, 52, and 37.5 years,
      respectively. The average tumor sizes in these groups were 13.46, 13.82, and 16
      cm, respectively. There was no statististically significant difference between
      the Group A and B patients with respect to tumor size (P = 0.94) or age (P =
      0.96) (t test). Eight of the 11 patients in groups A and B were FIGO stage 3 or 4
      at presentation. Five (83%) of the 6 group A patients and 2 (40%) of the 5 group
      B patients died of their disease an average of 4.8 and 3.5 months after initial
      evaluations respectively. However, the 2 patients who presented with stage 1
      disease (and with follow-up information) have shown no evidence of tumor
      recurrence at an average of 26 months' follow-up. It is concluded that ovarian
      osteosarcomas are rare malignancies that are frequently associated with teratomas
      but may be seen in pure form. Unlike osseous osteosarcoma whose peak age of
      incidence is in the second decade, ovarian osteosarcomas occur at an older age
      group. Most patients have advanced stage disease at presentation. Ovarian
      osteosarcomas have a high (>60%) case fatality rate; analysis of the reported
      cases suggests that the latter is attributable to the advanced stage at which
      most patients present, as there are no reported cases of patients with stage 1
      disease whose diseases have recurred after surgical resection or who have died of
      their disease.

PMID- 17197893
TI  - Silent corticotroph cell pituitary adenoma in a struma ovarii.
AB  - This is the first report of a silent corticotroph cell pituitary adenoma arising
      in a struma ovarii. The patient, a 79-year-old woman, was found to have an
      asymptomatic left-sided adnexal mass confirmed by vaginal sonography to be a
      complex cystic and solid tumor. Pathological analysis demonstrated an 8-cm
      partially cystic struma ovarii in which there was a focus of predominantly
      basophilic adenohypophyseal cells arranged in a diffuse pattern, adjacent to
      mature neural tissue containing numerous Herring bodies. The epithelial lining
      cells of the colloid-filled small and cystic follicles were immunoreactive for
      thyroglobulin. The pituitary cells were predominantly immunoreactive for
      adrenocorticotropic hormone, in addition to synaptophysin.

PMID- 17197894
TI  - Recurrent gynandroblastoma of ovary-A case report: a molecular and
      immunohistochemical analysis.
AB  - Gynandroblastoma is a rare ovarian tumor that is composed of both Sertoli cells
      and granulosa cells. Only 23 cases have been reported in the literature, and
      recurrence has never been described. We report the first case of a recurrent
      gynandroblastoma along with its molecular analysis and immunohistochemical
      studies. A 49-year-old Gravida 0 woman with a 10-year prior diagnosis of ovarian
      mixed stromal tissue tumor (well-differentiated Sertoli cell and granulosa cell
      tumor) and staging laparotomy, presented now with a retroperitoneal mass and an
      elevated inhibin level. CT scan was suspicious for recurrence. The patient had no
      prior adjuvant therapy. The histomorphological features of the recurrent tumor
      had both Sertoli cell and granulosa cell tumor. The molecular analysis of both
      primary and recurrent tumor showed minor genetic instability in the 17q12.2 gene
      locus with no dedifferentiation or progression, which is consistent with a low
      grade tumor. The immunohistochemical staining profile showed positivity for CD99,
      inhibin, calretinin, and vimentin; focal positivity for cytokeratin AE1/AE3 and
      negative for EMA and melan-A. All the previously mentioned immunostainings
      support the diagnosis. We report the first case of a recurrent gynandroblastoma
      10 years after initial presentation along with its molecular analysis and
      immunohistochemical studies.

PMID- 17197895
TI  - Primary synovial sarcoma in fallopian tube: case report and literature review.
AB  - Synovial sarcoma, a malignant mesenchymal neoplasm, occurs mostly near the joints
      of the extremities and occasionally outside the joint such as lung. We report a
      case of soft tissue sarcoma arising in the fallopian tube origin that showed
      characteristic pathological appearance of biphasic synovial sarcoma. Molecular
      analysis detected a fusion gene transcript of synovial sarcoma translocation
      (SYT) gene from chromosome 18 and synovial sarcoma X chromosome breakpoint 1
      (SSX1) gene, which is believed to pathognomonic for synovial sarcoma of joint
      origin. Recurrent abdominal tumor, observed at 12 month after the initial surgery
      and following chemotherapy using doxorubicin, cisplatin and ifosfamide, partially
      responded to chemotherapy using paclitaxel and carboplatin and, then, optimal
      surgery was performed. This is the first report of a synovial sarcoma arising in
      the fallopian tube.

PMID- 17197896
TI  - Occurrence of endometrial glandular dysplasia precedes uterine papillary serous
      carcinoma.
AB  - Endometrial glandular dysplasia (EmGD) is a newly defined entity that is commonly
      and specifically associated with serous endometrial intraepithelial carcinoma and
      uterine papillary serous carcinoma (UPSC). Endometrial glandular dysplasia has
      been proposed as a true precancerous lesion of UPSC based on our recent studies
      showing morphological and molecular linkages between these 2 lesions. The present
      report is to examine if EmGD occurs before UPSC development and to define the
      period from the occurrence of EmGD to a full-blown UPSC by studying their
      clinicopathologic features in a retrospective setting. A total of 250 UPSC and
      258 benign cases were used as initial study source. To identify if EmGD existed
      before the development of UPSC, we blindly reviewed all available endometrial
      biopsies from a period of 3 months or earlier before hysterectomies. These
      included an available pool of 27 biopsy specimens from UPSC group and 29 samples
      from benign control group. Any endometrial abnormalities, which morphologically
      qualified as EmGD as defined previously in preceding biopsies were recorded.
      Among all endometrial biopsies before hysterectomies, we morphologically
      identified a total of 10 EmGD cases; 9 (33%) of 27 were from UPSC group and 1
      (3.5%) of 29 were from benign control group. All 10 morphologically diagnosed
      EmGD cases showed a high p53 staining score (>/=5) except 1 noncontributory from
      UPSC group and 1 from the benign control group with a score of 0. A high MIB-1
      index score was seen in all EmGD cases, whereas low index was found in
      morphologically benign biopsies. The main purpose of this study is to report
      these retrospectively identified EmGD cases. The period from identifying EmGD to
      the presence of either a serous endometrial intraepithelial carcinoma or a full
      blown UPSC ranged from 16 to 98 months with an average of 33 months. We conclude
      that occurrence of EmGD precedes the development of UPSC. The findings support
      our recently proposed UPSC development model, in which EmGD is likely to be a
      precursor lesion of UPSC. Further studies are needed to address issues in regard
      to molecular and cellular mechanisms, reversibility, risk of UPSC development,
      and clinical management of EmGD.

PMID- 17197897
TI  - Expression of organic cation transporter SLC22A16 in human endometria.
AB  - SLC22A16 is one of newly isolated organic cation transporters, which is
      responsible for uptake and transport of adriamycin into cells. Adriamycin is one
      of the key drugs for treatment of endometrial cancer. Therefore, we examined
      expression of SLC22A16 in human endometrium and its disorders. Protein and mRNA
      expression levels of SLC22A16 were examined in 124 endometrial cancer specimens,
      25 normal endometrial tissue samples (15 in proliferative phase, 10 in secretory
      phase), and 7 endometrial cancer cell lines using immunohistochemical analysis
      and reverse transcription-polymerase chain reaction. Changes in SLC22A16 mRNA
      expression level after progesterone exposure were also examined.
      Immunohistochemical analysis showed that SLC22A16 protein was highly expressed in
      endometrium during the normal secretory phase, but its level was significantly
      reduced in the proliferative phase. SLC22A16 protein was detected in 59 of 124
      (48%) endometrial cancer specimens and 3 of 7 (43%) endometrial cancer cell
      lines. The mRNA levels measured by quantitative reverse transcription-polymerase
      chain reaction were comparable with levels of protein expression. Furthermore,
      SLC22A16 mRNA levels were increased in endometrial cancer cell lines in the
      presence of progesterone. In conclusion, SLC22A16 is expressed in various
      endometrial tissues. Its expression level is high during the secretory phase and
      may be regulated by progesterone. Our findings also suggest that it may be
      possible to use progestins to increase the response of endometrioid endometrial
      carcinoma with SLC22A16 expression to adriamycin-based chemotherapeutic regimens.

PMID- 17197898
TI  - Mucin genes (MUC2, MUC4, MUC5AC, and MUC6) detection in normal and pathological
      endometrial tissues.
AB  - Changes in the composition and physical properties of the mucous gel covering the
      endometrial surface are detected during the menstrual cycle and in pathological
      conditions. The aim of this study is to analyze the expression patterns of the
      11p15 secreted mucins, MUC2, MUC5AC, and MUC6, and the membrane-bound mucin MUC4
      in proliferative and secretory normal endometrium, simple and complex
      hyperplasia, and endometrial adenocarcinoma. A total of 98 samples, 19 of normal
      endometrium (11 proliferative and 8 secretor), 44 of endometrial hyperplasia (23
      simple, 21 complex), and 35 of endometrial endometrioid adenocarcinomas were
      analyzed by immunohistochemical techniques using specific antimucin antibodies.
      In the endometrial proliferative glandular epithelium, only MUC4 is detected
      (36.3% cases). During the secretory phase, increased levels of MUC2 are found
      (37.5%), whereas MUC4 is less detected (12.5%). In simple hyperplasia, higher
      levels of mucins are expressed in the endometrial glands: MUC2 is detected in
      8.7%, MUC4 in 43.4%, and MUC5AC and MUC6 in 13% of the samples, whereas in
      complex hyperplasia, decreased levels of mucin expression are found: MUC2 and
      MUC5AC are not detected, and MUC4 (28.5%) and MUC6 (20.4%) are positive. In
      endometrial adenocarcinoma, MUC4 is highly detected (77.1%) and increased levels
      of MUC5AC and MUC6 are found (61.7% and 48.5%), whereas MUC2 is poorly detected
      (8.5%). These findings suggest that during endometrial neoplasic transformation,
      increased levels of MUC4, MUC5AC, and MUC6 are detected, whereas MUC2 is only
      significantly detected in the secretory endometrium.

PMID- 17197899
TI  - Alpha-fetoprotein-producing serous carcinoma of the uterus metastasizing to the
      ovaries, mimicking primary ovarian yolk sac tumor: a case report and review of
      the literature.
AB  - In the uterus, most alpha-fetoprotein (AFP) producing neoplasms belong to the
      categories of malignant mixed muellerian tumor, hepatoid carcinoma, and yolk sac
      tumor. We describe the case of a 44-year-old woman who presented with vaginal
      bleeding, pelvic mass, and preoperative elevated AFP serum level, clinically
      suggestive of a primary ovarian yolk sac tumor. However, histological examination
      revealed a uterine AFP-producing papillary serous carcinoma, which has
      metastasized to the ovaries. Upon review of the literature on primary endometrial
      neoplasms with AFP production, 2 categories with possibly different histogenesis
      and biological behavior become evident: the primary yolk sac tumor of the uterus
      in young patients (range, 24-49 years; mean, 34 years) and the common high grade
      endometrial carcinoma with yolk sac dedifferentiation or aberrant AFP production
      in elderly patients (range, 55-69 years; mean, 63.7 years). In addition to being
      only the second case of uterine AFP-producing papillary serous carcinoma, this
      case is unusual for its clinical and radiological presentation as well as the
      relatively young age of the patient.

PMID- 17197900
TI  - Utility of p16INK4a, CEA, Ki67, P53 and ER/PR in the differential diagnosis of
      benign, premalignant, and malignant glandular lesions of the uterine cervix and
      their relationship with Silverberg scoring system for endocervical glandular
      lesions.
AB  - Early detection of premalignant and malignant glandular lesions of the uterine
      cervix and their distinction from benign mimics is crucial but sometimes
      difficult. In this study, we investigated utility of expression of p16, CEA,
      Ki67, p53 and ER/PR in evaluating the benign, premalignant, and malignant
      glandular lesions of the uterine cervix. A total of 35 cervical cone or LEEP
      cases were collected including 14 adenocarcinoma in situ (AIS), 7 endocervical
      glandular dysplasia (EGD), and 14 benign mimics (BM). A histological score for
      each case according to the criteria proposed by Silverberg group was assigned
      independently by 4 pathologists. Formalin-fixed, paraffin-embedded sections were
      immunostained with p16, CEA, p53, Ki67, and ER/PR. Immunoreactivity was scored
      based on intensity (0 = none, 1 = mild, 2 = moderate, 3 = marked) and percentage
      of cells staining (0 = <1%,1 = 2-10%, 2 = 11-40%, 3 = >40%). A comparison of
      histological scores and immunoscores in 3 diagnostic categories was analysed. The
      histological scores assigned independently by 4 pathologists were all equal or
      above 6 for AIS, between 3 and 5 for EGD, and equal or below 3 for BM. There was
      increased expression of p16 and CEA in EGD compared with BM (P < 0.05), with
      further increase in expression of these markers in AIS compared with EGD (P <
      0.05). Ki67 expression was significantly increased in AIS compared to EGD (P <
      0.05) as well as compared to BM (P < 0.05). Ki67 expression was only slightly
      increased in EGD as compared to BM. There was a loss of ER/PR in cervical AIS,
      but not in EGD. Our results indicate that the Silverberg scoring system is a
      useful tool in differential diagnosis of cervical glandular lesions for increased
      diagnostic accuracy and interobserver agreement. Most cervical glandular lesions
      can be differentiated by using a combination of histological scores with a panel
      of immunomarkers.

PMID- 17197901
TI  - Immunoprofile of endocervical and endometrial stromal cells and its potential
      application in localization of tumor involvement.
AB  - To evaluate and compare the immunophenotype of endocervical and endometrial
      stromal cells and to asses its potential application in tumor localization.
      Paraffin sections of benign endocervix (n = 24), benign endometrium (n = 33),
      endocervical adenocarcinoma (n = 9), endometrial carcinoma (n = 13), and
      endometrial hyperplasia (n = 16) were stained with antibodies to CD10, Wilms
      Tumor-1, CD34, smooth muscle actin, and factor XIIIa by immunohistochemistry. In
      16 cases, lower uterine segment was also available. Immunoreactivity of stromal
      cells was recorded as positive (>/=50% staining), focally positive (>/=5%-<50%)
      or negative (<5%). Endocervical stromal cells (ECSC) in either benign or
      malignant cervical epithelial lesions were predominantly CD34/CD10 (CD34 dominant
      immunophenotype). Endometrial stromal cells (EMSCs) in either benign or malignant
      epithelial lesions were primarily CD34/CD10 (CD10 dominant immunophenotype).
      Expression of Wilms Tumor-1 was decreased in EMSC of the EMCA when compared to
      their counterpart in endometrial hyperplasia. There was no differential
      expression of smooth muscle actin and factor XIIIa identified between ECSC and
      EMSC. The immunophenotypes of the ECSC and EMSC overlapped in the lower uterine
      segment. The functional status of the endometrium had no effect on the
      immunoprofile. The pattern of CD34 and CD10 immunostaining in stromal cells might
      be helpful in determining tumor involvement in uterine and cervical sites.

PMID- 17197902
TI  - An immunohistochemical study of CD1a and CD83-positive infiltrating dendritic
      cell density in cervical neoplasia.
AB  - Cervical carcinoma is the second leading cancer in women in Malaysia, after
      breast cancer. Human papillomavirus (HPV) has been implicated in the development
      of dysplasia or cervical intraepithelial neoplasia and progression to squamous
      cell carcinoma. Because of the confinement of the human papillomavirus infection
      within the epithelial layer, the presence of dentritic cells or Langerhans cells
      in epithelial layer of the ectocervix is paramount in producing immune response.
      The mature dentritic cells express CD83 and high CD40/80/86, whereas the immature
      cells express CD1a and low CD40/80/86. By identifying CD1a and CD83,
      theoretically, both immature and mature dentritic cell populations can be
      studied. In view of the facts, we investigated the infiltrating cell density of
      mature and immature dentritic cells in cervical neoplasia.

PMID- 17197903
TI  - The lack of laminin-5 as a prognostic marker in low-grade cervical squamous
      intraepithelial lesions: correlation with clinical follow-up data.
AB  - Low-grade cervical squamous intraepithelial lesions have a high rate of
      spontaneous regression but may undergo surgical treatment (cone biopsy) in case
      of persistence of the lesion or discrepancy between Pap-smear diagnosis and
      biopsy diagnosis. This may sometimes lead to surgical complications and/or
      adverse effects on fertility. Thus, the present study was designed to investigate
      the potential of laminin-5 as a sensitive molecular marker identifying cervical
      intraepithelial neoplastic lesions (CIN), which are likely to regress and
      ultimately spare women unnecessary surgical procedures. Cervical punch biopsy
      samples from 65 women with either a CIN I or a CIN II were evaluated for the
      expression of laminin-5 by immunohistochemistry. All study subjects agreed to a
      conservative clinical management and were frequently followed-up (median follow
      up time 237 days) to evaluate for changes in the dysplastic lesion. Laminin-5
      staining results were correlated with patient's characteristics as well as
      clinical follow-up data. Laminin-5 expression was detected in 16 of 40 CIN I
      (40%) lesions, 2 of 21 CIN II (9.5%) lesions and none of 4 reclassified CIN III
      lesions. Within positive cases, laminin-5 expression was localized to the
      cytoplasm of the dysplastic cells. The laminin-5 expression was significantly
      associated with the grade of CIN lesion (p < 0.005). Correlations with patient's
      characteristics were not statistically significant except for education and
      ectocervical smear diagnosis. No significant associations were noted between
      laminin-5 expression and either regression, persistence or progression of the CIN
      lesions. These data indicate that laminin-5 is not a useful diagnostic adjunct in
      histopathology for the identification of CIN lesions with progressive capacity.

PMID- 17197904
TI  - Wegener's granulomatosis of the uterine cervix: a case report and review of the
      literature.
AB  - In this report, we present the case of a 32-year-old woman with Wegener's
      granulomatosis of the uterine cervix, review the literature, and discuss the
      differential diagnosis.

PMID- 17197905
TI  - Vulvar varices: an uncommon entity in surgical pathology.
AB  - Varicose veins in the vulvar and perivulvar area are seen in 4% of women. Most of
      them are secondary to pregnancy and usually regress spontaneously. Vulvar
      varicose veins are rare in nonpregnant women. When present, they can be seen
      alone, associated with leg varices or associated with venous malformations of the
      labia, clitoral area, or vagina with or without arteriovenous malformations on
      the limbs or trunk (Klippel-Trenaunay-Weber syndrome and Parkes-Weber syndrome).
      In some cases, vulvar varices are seen as part of the so-called "pelvic
      congestion syndrome." Clinically, vulvar varices may present as small isolated
      protrusions, mainly in the labia majora, or as large masses, involving the vulva
      and even the perivulvar area. The treatment of choice of vulvar varices seen
      during pregnancy is conservative and symptomatic. Surgical pathologists need to
      be aware of the existence of vulvar varicose veins and its possible presence in
      biopsy specimens. Vulvar varicose veins can be misdiagnosed clinically as cysts
      or masses mainly in the Bartholin gland area. Correct diagnosis of the lesion is
      important to determine appropriate therapy and to recognize the possibility of
      associated anatomical or pathological problems.

PMID- 17197906
TI  - A closer look at nurses' salaries.
AB  - Here's a summary of the results of Nursing2006's seventh annual nationwide
      survey.

PMID- 17197907
TI  - How to find a nursing job online.
AB  - Find the best job in the best facility in the best location for you, all from the
      comfort of your own home.

PMID- 17197908
TI  - Reentering the workforce confidently.
AB  - Thinking of coming back to nursing? Your timing is great.

PMID- 17197909
TI  - Professional portfolio: a snapshot of your career.
AB  - Here's how to create a list of your personal and professional goals, growth, and
      achievements.

PMID- 17197910
TI  - Guide to nursing organizations.
AB  - Keep a copy of this chart handy in case you need to contact these nursing
      organizations.

PMID- 17197911
TI  - 5 reasons to consider travel nursing.
AB  - Personal and professional growth-not to mention a chance to explore the country
      await nurses who decide to give travel nursing a try.

PMID- 17197912
TI  - Understanding the challenges of e-learning.
AB  - Thinking about taking an online course or program? Here's what you should know
      before you sign up.

PMID- 17197913
TI  - Why you should consider working at a magnet hospital.
AB  - Here are the reasons I love working at a Magnet facility.

PMID- 17197914
TI  - Atypical lipomatous tumor, its variants, and its combined forms: a study of 61
      cases, with a minimum follow-up of 10 years.
AB  - Sixty-one cases of neoplasms composed wholly or in part of atypical lipomatous
      tumor were reviewed. Minimum follow-up was 10 years. The cases were divided into
      4 groups based on the findings in the initial excision specimen: conventional
      atypical lipomatous tumor (n=15), cellular atypical lipomatous tumor (n=21),
      dedifferentiated liposarcoma (n=24), and atypical lipomatous tumor with a
      pleomorphic liposarcoma-like component (n=1). The term "cellular atypical
      lipomatous tumor" was applied to atypical lipomatous tumors having areas of
      increased cellularity that when non-lipogenic lacked the 5 mitotic figures per 10
      high-power fields (maximal rate) required for a dedifferentiated component and
      when lipogenic fell short of being truly pleomorphic liposarcoma-like. Myxoid
      regions within this spectrum sometimes had prominent or even plexiform
      vascularity, creating a resemblance to myxoid liposarcoma especially when
      interspersed small fat cells were present. The most important prognostic factor
      was tumor location, as none of the 12 patients with a subcutaneous or
      intramuscular neoplasm died of tumor. Among the 49 patients with neoplasms of
      central body sites (mostly retroperitoneum), those with dedifferentiated
      liposarcoma had significantly shorter survival (median 77 mo) than those with
      cellular (median 142 mo) or conventional (median 209 mo) atypical lipomatous
      tumor, whereas there was no statistically significant difference between the
      latter 2 categories. Patients with atypical lipomatous tumor (either cellular or
      conventional) in central body sites had significantly shorter survival if the
      tumor transformed into dedifferentiated liposarcoma in recurrence, and,
      conversely, those with central body site dedifferentiated liposarcoma had
      significantly longer survival if it recurred as atypical lipomatous tumor.
      Metastasis (7 cases) occurred only when the initial specimen or a recurrence
      demonstrated dedifferentiated liposarcoma.

PMID- 17197915
TI  - Calcareous lesions of the distal extremities resembling tumoral calcinosis
      (tumoral calcinosislike lesions): clinicopathologic study of 43 cases emphasizing
      a pathogenesis-based approach to classification.
AB  - Herein, we analyze the clinicopathologic features of 46 distal extremity lesions
      that have histologic features similar to conventional tumoral calcinosis (tumoral
      calcinosislike; TC-L). The study included 31 females and 12 males (whites:non
      whites>3:1) ranging in age from 1 to 91 (mean, 39; median, 42) years. The lesions
      presented in fingers (n=20), feet (n=10), wrist (n=6), hands (5), toes (n=4), and
      ankle (n=1) were solitary in all but 5 patients and ranged in size from 0.3 to
      4.5 (mean, 1.6; median, 1.4) cm. Chief initial complaints included presence of a
      painful (n=16) or asymptomatic (n=7) mass, and limitation of joint mobility
      (n=3). Pertinent clinical associations included antecedent trauma (n=7),
      scleroderma (n=3), long-standing osteoarthritis (n=3), bony deformities (n=5),
      including 2 infants with congenital hand malformations, and chronic renal failure
      (n=2). Patients were stratified into one of the 3 recognized clinical settings of
      TC: primary normophosphatemic (n=17), secondary (n=5), or primary
      hyperphosphatemic TC (n=1). The 20 remaining patients were placed in an
      "indeterminate TC" category. Most lesions were located in tenosynovial/fascial
      tissue, but 13 lesions involved dermis and 1 was intra-articular. Histologically,
      the process consisted of multiple cystic or cleftlike spaces bordered by
      histiocytes, osteoclastlike giant cells, and a variable inflammatory infiltrate
      and containing fibrin, granular calcific debris, and calcospherites. Pools of
      calcific debris bordered by sclerotic collagen and a sparse cellular element
      predominated in 4 cases. Cartilaginous metaplasia was identified in 10 lesions
      and evidence of hemorrhage or specific injury was observed in 12 examples. Follow
      up data for 22 patients (interval range, 1 to 30 y; median, 6 y) revealed 17
      individuals with no evidence of recurrent disease or the development of
      additional lesions after simple (local) excision. One patient (indeterminate TC)
      required reexcision of a thumb mass 1 year after surgery. All 3 scleroderma
      patients developed additional TC-L lesions. Acral TC-L lesions are histologically
      similar to conventional TC, but present as smaller size lesions. Most TC-L
      lesions are closely aligned with primary normophosphatemic or secondary TC. Acral
      TC-L lesions may be the first manifestation of scleroderma, where the process has
      the potential to follow an unrelenting course.

PMID- 17197916
TI  - Nonsmall cell lung carcinoma with neuroendocrine differentiation--an entity of no
      clinical or prognostic significance.
AB  - The existence of non-small cell lung carcinoma with neuroendocrine
      differentiation as a distinct entity and its relevance for prognostic and
      treatment purposes is controversial. This study assesses the frequency and
      biologic and prognostic significance of neuroendocrine (NE) expression of
      synaptophysin (SNP), chromogranin (Ch), and neural cell adhesion molecule (N-CAM)
      using tissue microarray (TMA) and immunohistochemistry. Six hundred nine nonsmall
      cell lung carcinomas (NSCLCs) were reviewed for subclassification. TMA blocks
      were made using duplicate 0.6-mm-diameter tissue cores and slides stained with
      SNP, Ch, and N-CAM. Immunoreactivity was considered if 1% or more of tumor cells
      were positive. Hematoxylin and eosin-stained sections were subclassified as: 243
      adenocarcinoma (ACA), 272 squamous cell carcinoma (SCC), 35 large cell carcinoma,
      32 non-small cell carcinoma NOS, and 6 other (carcinosarcoma, giant cell
      carcinoma). Positivity for either marker was identified in 13.6% of NSCLC
      (76/558). NSCLC showed reactivity for Ch in 0.4% of cases (2/524), for SNP in
      7.5% of cases (39/521) and for N-CAM in 8.6% of cases (44/511), whereas only 0.2%
      of cases (1/517) showed coexpression of SNP and Ch and none of all 3 markers. The
      assessment of NE differentiation in NSCLC is unnecessary and expensive and is of
      no clinical or prognostic significance. SNP or N-CAM stains a small minority of
      NSCLC, whereas Ch immunoreactivity is less common. Positivity for any 2 NE
      markers is rare. SNP is more likely to be expressed in adenocarcinoma (P=0.01)
      and N-CAM in squamous-cell carcinoma (P=0.008). Otherwise there was no
      correlation between immunoreactivity and tumor morphology. Disease specific and
      overall survival is not influenced by NE differentiation and therefore non-small
      cell lung carcinoma with neuroendocrine differentiation should not be a subclass
      distinct from the other NSCLC.

PMID- 17197917
TI  - p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the
      detection of high-risk HPV in atypical squamous metaplasia.
AB  - In situ hybridization (ISH) assays for high-risk human papillomavirus (HR-HPV)
      and immunohistochemical (IHC) assays for surrogate markers such as p16 can be
      useful in detecting HR-HPV in cervical dysplasia, but the use of these markers in
      problematic cervical biopsies has not been well-established. We evaluated 3
      chromogenic ISH assays (Ventana INFORM HPVII and HPVIII and DakoCytomation
      GenPoint) in conjunction with p16 IHC and HPV polymerase chain reaction in a
      study set consisting of 12 low-grade squamous intraepithelial lesions, 16 high
      grade squamous intraepithelial lesions, and 30 benign cervix samples. A test set
      of 28 cases of atypical squamous metaplasia were also evaluated withVentana
      HPVIII ISH and p16 IHC. In the study set, the sensitivity of the DakoCytomation
      ISH assay (which detects HPV subtypes 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59,
      and 68) was similar to the Ventana HPVII assay but less than that of the Ventana
      HPVIII ISH assay (both of which detect HPV subtypes 16, 18, 31, 33, 35, 39, 45,
      51, 52, 56, 58, and 66) and less than p16 IHC (55.6% vs. 53.6 vs. 69.2% vs.
      82.1%). All HPV ISH assays exhibited 100% specificity. p16 reactivity consisted
      of 2 patterns: focal strong and diffuse strong. Because focal strong p16
      reactivity was identified in benign squamous epithelium (6.7% cases) and
      dysplastic epithelium, it was considered an equivocal result and only diffuse
      strong reactivity was considered to be specific for the presence of HR-HPV. In
      the squamous intraepithelial lesions study set, the difference in sensitivity
      between Ventana HPVIII ISH and p16 was not statistically significant. However, in
      the atypical squamous metaplasia test set cases, p16 reactivity (focal strong and
      diffuse strong) was significantly more sensitive than Ventana HPVIII ISH in
      correlating with the presence of human papillomavirus as detected by polymerase
      chain reaction (83.3% vs. 33.3% P=0.004). Because focal strong p16 reactivity is
      less specific, cases with this staining pattern are considered atypical and
      require further evaluation by other means. Overall, p16 IHC is considered the
      best candidate for the initial assessment of cervical biopsies that are
      histologically indeterminate for dysplasia given its wide availability,
      comparative ease of interpretation, and high sensitivity and specificity.

PMID- 17197918
TI  - Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum
      and immunophenotypic characteristics in 61 tumors of the salivary glands and
      upper aerodigestive tract.
AB  - To further define the clinicopathologic spectrum of epithelial-myoepithelial
      carcinoma (EMCa), we report the gross, histologic, and immunophenotypic
      characteristics of 61 tumors seen within a 30-year-period. The mean age at
      presentation was 60.9 years, with a female predominance (1.5:1). The most common
      sites were parotid (62.1%), sinonasal mucoserous glands (10.3%), palate (8.6%),
      and submandibular (8.6%). Most EMCas showed a characteristic nodular/multinodular
      growth pattern and classic biphasic tubular histology. However, new morphologies
      in EMCa such as ancient change (8.2%), "Verocay"-like change (3.3%), and
      sebaceous differentiation (13.1%) were noted. Specific histologic variants were
      dedifferentiated EMCa (3.3%), oncocytic EMCa (8.2%), EMCa ex pleomorphic adenoma
      (1.6%), double-clear EMCa (3.3%), and EMCa with myoepithelial anaplasia (3.3%).
      All cytokeratin cocktails selectively highlighted the epithelial component well.
      Of the myoepithelial markers, p63, smooth muscle actin and vimentin performed
      best. Bcl-2 and c-kit were frequently positive (66.7% and 69.2%, respectively).
      p53 was highly expressed only in 1 dedifferentiated EMCa. The recurrence rate was
      36.3% (median disease-free survival 11.34 y), but death was rare with 5-year and
      10-year disease-specific survivals of 93.5% and 81.8%, respectively. The most
      important univariate predictors of recurrence were margin status (log rank
      P=0.006), angiolymphatic invasion (P=0.002), tumor necrosis (P=0.004), and
      myoepithelial anaplasia (P=0.038). Thus, EMCa is generally a low-grade tumor with
      a broader morphologic spectrum than previously thought, with several key features
      predictive of recurrence. Immunohistochemistry can aid diagnosis by highlighting
      the biphasic nature of the tumor.

PMID- 17197919
TI  - Excellent interobserver agreement on grading the extent of residual carcinoma
      after preoperative chemoradiation in esophageal and esophagogastric junction
      carcinoma: a reliable predictor for patient outcome.
AB  - The extent of residual carcinoma in resected esophageal cancer specimens after
      preoperative chemoradiation is a predictor of survival according to 3 groups: P0
      (0% residual carcinoma), P1 (1% to 50% residual carcinoma), and P2 (>50% residual
      carcinoma). However, the interobserver variation and reliability of this
      classification has not been evaluated among different pathologists. Histologic
      hematoxylin and eosin-stained slides from 60 coded cases of esophageal
      adenocarcinomas treated with preoperative chemoradiation followed by
      esophagectomy were independently reviewed by 6 pathologists from 4 different
      institutions for extent of residual carcinoma and ypT stage. Interobserver
      agreement was analyzed by kappa (kappa) statistics, and grading of extent of
      residual carcinoma and ypT stage based on individual and consensus gradings were
      correlated with patients' survival. The interobserver agreement was excellent for
      extent of residual carcinoma (kappa=0.84, Kendall's W=0.92; P<0.000001) and was
      good for ypT stage (kappa=0.71, Kendall's W=0.88; P<0.000001). Agreement was
      excellent for all categories of residual carcinoma: P0 (kappa=0.87), P1
      (kappa=0.81), and P2 (kappa=0.85). Extent of residual carcinoma was a significant
      predictor for overall survival based on individual pathologist grading (all P
      values <0.03), and consensus grading (13 P0, 32 P1, and 15 P2), P=0.004;
      independent of ypT and ypN stages in multivariate analysis (P=0.02). Our results
      indicate that after preoperative chemoradiation in esophageal cancer there is
      excellent interobserver agreement among pathologists on grading extent of
      residual carcinoma. The extent of residual carcinoma is a reliable and
      reproducible predictor of survival; this grading system may allow a novel and
      early means of comparing outcomes after different neoadjuvant treatment regimens.

PMID- 17197920
TI  - Molecular analysis of the JAZF1-JJAZ1 gene fusion by RT-PCR and fluorescence in
      situ hybridization in endometrial stromal neoplasms.
AB  - Nonrandom cytogenetic abnormalities of chromosomes 6, 7, and 17 have been
      reported within low-grade endometrial stromal sarcomas (LGESSs), and among these
      abnormalities, the t(7;17)(p15;q21) is the most common aberration described.
      Previously we had shown that this translocation joins 2 genes, JAZF1 and JJAZ1,
      located on chromosomes 7 and 17, respectively. To determine the frequency of the
      t(7;17), we analyzed 4 stromal nodules and 24 LGESS by both reverse transcriptase
      polymerase chain reaction and fluorescence in situ hybridization (FISH). In
      addition, we examined 4 cases of highly cellular leiomyoma, a benign morphologic
      mimic of LGESS. Overall, evidence for the JAZF1-JJAZ1 fusion was found in 60% of
      endometrial stromal neoplasms analyzed (8/16 ESS and 4/4 stromal nodules). One
      LGESS demonstrated only rearrangement of 7p15 by FISH analysis and karyotypic
      analysis of this case showed t(6;7)(p21;p15). The fusion was not detected in any
      highly cellular leiomyomas. Our data suggest that the JAZF1-JJAZ1 fusion is a
      frequent, although nonuniform, feature of endometrial stromal neoplasia,
      irrespective of benign versus malignant classification and smooth muscle
      differentiation. In addition, the detection of the fusion by reverse
      transcriptase-polymerase chain reaction or FISH for JJAZ1 at 7p15 may be
      diagnostically useful.

PMID- 17197921
TI  - Carcinoma cuniculatum: a distinctive variant of penile squamous cell carcinoma:
      report of 7 cases.
AB  - We are reporting a peculiar variant of penile squamous cell carcinoma (SCC)
      characterized by its peculiar deeply penetrating and burrowing pattern of growth.
      This low grade, verruciform penile neoplasm is similar to the plantar epithelioma
      cuniculatum originally described by Ayrd in 1954. Clinical and pathologic
      features of 7 patients are presented. There were 7 partial penectomies and 4
      bilateral inguinal node dissections. The mean patient's age was 77 years.
      Grossly, the tumors were white to gray, exo-endophytic, and papillomatous with a
      cobblestone or spiky appearance. All cases affected the glans and extended to
      coronal sulcus and foreskin (average size was 6.3 cm). The hallmark of the lesion
      was noted on cut surface where there were deep tumoral invaginations forming
      irregular, narrow, and elongated neoplastic sinus tracts connecting the surface
      of the neoplasm to deep anatomic structures. The neoplasm invaded through lamina
      propria and corpus spongiosum and grew along the loose connective tissue of Buck
      fascia to involve the tunica albuginea and corpora cavernosa (average depth was
      32 mm). Deeply invasive keratin filled cysts or crypts, on serial sections,
      showed to be connected to the surface tumor. Fistulization to the skin was also
      noted. Microscopically, the lesions corresponded to well-differentiated
      carcinomas with bulbous front of invasion. There were focal areas of higher
      histologic grade and more infiltrative and jagged borders in 4 cases. Inguinal
      nodes were negative in 4 patients in which groin dissection was performed.
      Carcinoma cuniculatum is a variant of penile SCC with distinctive growth pattern
      and should be distinguished from other verruciform tumors such as the verrucous,
      papillary, and warty carcinomas. Unlike most subtypes of penile SCCs and despite
      the deep invasion, none of the tumors showed groin or systemic dissemination at
      time of diagnosis.

PMID- 17197922
TI  - HLA-A, -B, -C expression in colon carcinoma mimics that of the normal colonic
      mucosa and is prognostically relevant.
AB  - Whether human leukocyte antigen (HLA)-A, -B, -C expression has any predictive
      value on the prognosis of human malignancies remains controversial. Herein,
      monoclonal antibodies with preferential reactivity for HLA-A, HLA-B, and HLA-C
      (HCA2, HC10, and L31) were used to stain an archival collection of 291 formalin
      fixed/paraffin-embedded tissues, comprising neoplastic lesions from stages II and
      III colon carcinoma patients (n=165), and the uninvolved, morphologically normal
      mucosae from a subset (n=126) of these patients. Marked staining variability was
      detected not only in the tumors as in previous studies, but also in the normal
      paired mucosae. HLA-A, -B, -C expression was similar in approximately two thirds
      of the available 126 normal/neoplastic pairs, confirming in vivo our previous
      observation that most tumor cells mimic the HLA phenotypes of their normal
      counterparts. Both up and down-regulation occurred in the remaining third of the
      pairs, but did not coincide with high and low expression, respectively,
      conventionally evaluated on the tumor lesion only. Remarkably, a "paired"
      evaluation, but not high or low expression in the tumor, was predictive of the
      clinical outcome. Deviations from the expression in the normal paired mucosa
      (both increases and decreases) of HCA2-reactive class I molecules (possibly HLA
      A), and down-regulation of L31-reactive class I molecules (possibly HLA-C),
      particularly in tumors from stage II patients, correlated with poor 5-year
      overall and disease-free survival, hazard risk ranging from 2 to 6,
      approximately. Thus, a paired immunohistochemical comparison reveals a novel
      immune evasion strategy that may impact on the prognosis of colon carcinoma.

PMID- 17197923
TI  - Dysadherin expression as a significant prognostic factor and as a determinant of
      histologic features in synovial sarcoma: special reference to its inverse
      relationship with E-cadherin expression.
AB  - Dysadherin is a cancer-associated cell membrane glycoprotein, which down
      regulates E-cadherin and promotes metastasis. Synovial sarcoma is a very rare
      mesenchymal tumor that exhibits an epithelial profile. To confirm the diagnosis
      of synovial sarcoma, we evaluated several immunohistochemical markers, or
      detected SYT-SSX fusion gene transcript. We studied the clinicopathologic
      features in 92 synovial sarcoma patients and also assessed the
      immunohistochemical expression of dysadherin and E-cadherin to examine their
      possible association with histologic subtype and biologic behavior. Moreover,
      among 30 patients, for whom frozen materials were available, dysadherin mRNA
      expression was examined by reverse transcription-polymerase chain reaction and
      real-time quantitative reverse transcription-polymerase chain reaction analysis.
      Dysadherin-positive expression was significantly correlated with E-cadherin
      reduced expression (P=0.0004). Dysadherin-positive immunostaining was diffusely
      observed in the membranes of tumor cells in 30/68 (44%) patients with monophasic
      fibrous type and in 1/2 (50%) patients with poorly differentiated type. However,
      in biphasic tumors, dysadherin expression in the fibrous component was not
      diffusely observed, but often sporadically or focally observed [20/22 (91%)
      patients]. In addition, dysadherin mRNA expression in monophasic fibrous type was
      significantly higher than in biphasic type (P=0.0079). Synovial sarcoma patients
      with dysadherin expression survived for a significantly shorter time than those
      without dysadherin expression (P=0.0006). Patients with combined dysadherin
      positive expression and E-cadherin-reduced expression had a significantly worse
      prognosis than those with other combinations of dysadherin and E-cadherin
      expression (P=0.0007). SYT-SSX fusion gene transcript was detected in 39
      patients. In our series, SYT-SSX fusion type was found to have no correlation
      with histologic subtype, prognosis, or dysadherin expression. In multivariate
      analysis, dysadherin immunopositivity (P=0.0411) was an independent adverse
      prognostic factor, in addition to a high MIB-1 labeling index (> or =10%). We
      conclude that E-cadherin dysfunction by dysadherin is associated with reduced E
      cadherin expression and morphologic change from epithelioid to spindle phenotype.
      Dysadherin expression is considered to be one of the determinants of histologic
      subtype in synovial sarcoma. Moreover, dysadherin expression is an excellent and
      independent prognostic indicator.

PMID- 17197924
TI  - HMB-45 reactivity in conventional uterine leiomyosarcomas.
AB  - We studied the human melanoma black-45 (HMB-45) reactivity in 25 uterine
      leiomyosarcomas including 23 conventional and 2 myxoid variants. Eleven tumors
      were poorly differentiated, and 14 were well to moderately differentiated. Nine
      uterine leiomyosarcomas labeled with HMB-45 in 10% or less of the tumor cells.
      Six were poorly differentiated and 3 were well differentiated. Our study
      indicates that 36% of conventional leiomyosarcomas focally express HMB-45. HMB-45
      reactivity was more common in the poorly differentiated than in the well
      differentiated group of leiomyosarcomas. In light of our findings and of those
      recently reported in the literature, we believe that the term PEComa should not
      be used for uterine leiomyosarcomas with clear cells or for conventional
      leiomyosarcomas that stain positively with HMB-45.

PMID- 17197925
TI  - Epithelioid variant of myxofibrosarcoma: expanding the clinicomorphologic
      spectrum of myxofibrosarcoma in a series of 17 cases.
AB  - Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas of elderly
      patients and has a predilection for the limbs. Herein, we report a previously
      undescribed variant of MFS showing epithelioid morphology. Seventeen cases
      diagnosed as epithelioid MFS were retrieved from the authors' files from among
      570 cases of MFS. Hematoxylin and eosin-stained sections were reexamined and
      immunostains for pan-keratin (15 cases), S-100 protein (15), desmin (15), and
      alpha-smooth muscle actin (13) were performed. Nine patients were men and 8 were
      women (age range 43 to 89 y; median 63.5). Fifteen patients presented with a
      mass, and in 2 of these there was also pain. Duration of symptoms varied from 1
      to 24 months (median 3). Tumor size ranged from 2 to 15 cm (median 6.75). In 10
      cases, the tumor was located in subcutaneous tissue and in 6 cases it was
      subfascial. The majority of the tumors were located on the limbs (8 lower
      extremities and 6 upper extremities) followed by neck (1), scalp (1), and trunk
      (1). Follow-up was available for 14 patients (range 2 to 240 mo; median 16).
      Twelve patients were treated by surgery followed by chemotherapy and/or radiation
      (8 cases). One patient received chemotherapy after an incisional biopsy and 1
      patient was treated by surgery alone. Ten patients (71.4%) developed local
      recurrences. Seven patients (50%) developed metastases to lungs or
      retroperitoneum. Five patients (35.7%) have died of disease so far. Two patients
      were lost to follow-up. Morphologically, 14 cases were high grade, 2 were
      intermediate, and 1 was low grade. Tumors were characterized by a multinodular,
      infiltrating growth pattern with alternation of hypercellular and hypocellular
      myxoid areas; the latter showed prominent curvilinear vessels. Neoplastic cells
      were arranged singly and in small clusters in the myxoid areas or formed sheets
      in the hypercellular areas, where they showed epithelioid morphology with round
      nuclei, vesicular chromatin, prominent nucleoli, and moderate amounts of
      eosinophilic cytoplasm. The epithelioid areas were generally multifocal with
      admixed areas of conventional MFS. Immunostains were negative for all markers
      studied. Differential diagnosis included carcinoma, melanoma, myoepithelial
      carcinoma, pleomorphic liposarcoma, and pleomorphic rhabdomyosarcoma. In
      conclusion, epithelioid MFS is a rare variant of MFS, accounting for <3% of MFS
      in consultation material. Its natural history seems more aggressive than usual
      high-grade MFS, with approximately 70% local recurrence and 50% metastases, even
      within a relatively short follow-up period.

PMID- 17197926
TI  - Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large
      cell lymphoma from other types of diffuse large B-cell lymphoma.
AB  - Primary mediastinal large B-cell lymphoma (PMLBCL) is a recently identified
      subtype of diffuse large B-cell lymphoma (DLBCL) that is difficult to distinguish
      from other types of DLBCL on the basis of histologic features alone. We recently
      identified a molecular signature of PMLBCL that is distinct from other forms of
      DLBCL but shares features with classical Hodgkin lymphoma. This signature
      includes activation of the nuclear factor kappaB (NFkappaB) signaling pathway,
      which in part, acts through nuclear translocation of c-Rel containing NFkappaB
      transcriptional complexes, and subsequent expression of NFkappaB target genes
      such as tumor necrosis factor receptor-associated factor-1 (TRAF1). Using
      standard immunohistochemical techniques, we examined 251 large B-cell lymphomas
      (78 cases of PMLBCL and 173 cases of other types of DLBCL) to determine whether
      the expression patterns of c-Rel and TRAF1 could reliably distinguish between
      PMLBCL and other types of DLBCL. Robust nuclear c-Rel was present in 31 of 48
      (65%) cases of PMLBCL and 28 of 160 (18%) cases of DLBCL. In addition,
      cytoplasmic TRAF1 expression was seen in 48 of 78 (62%) cases of PMLBCL, but only
      20 of 173 (12%) cases of DLBCL. Finally, the combined expression of nuclear c-Rel
      and TRAF1 was seen in 24 of 45 cases (53%) of PMLBCL, but in only 3 of 156 cases
      (2%) of other types of DLBCL. Thus, the combined nuclear localization of c-Rel
      and the cellular expression of TRAF1 is a highly specific (specificity=98%) means
      to distinguish PMLBCL from DLBCL that is readily applicable to routine surgical
      pathology practice.

PMID- 17197927
TI  - Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults
      and frequently show c-KIT mutations.
AB  - Multifocal hyperplasia of interstitial cells of Cajal (ICC hyperplasia) is a
      precursor of hereditary gastrointestinal stromal tumors (GISTs) in patients with
      germline mutations of c-KIT or PDGFRA, but precursor lesions of sporadic GISTs
      have not been defined yet. Small hyalinizing stromal tumors of the proximal
      stomach (referred to in this study as GIST tumorlets) were collected
      prospectively from 98 consecutive autopsies and additional cases were retrieved
      from surgical pathology files (total n=57). GIST tumorlets were grossly
      detectable in 22.5% consecutive autopsies performed in individuals older than 50
      years. All lesions were located in the cardia, fundus, or proximal body, and
      ranged in size from 1 to 10 mm (4 mm). Similar lesions were not detected in the
      antrum, duodenum, and the remainder of the bowel. Histologically, the spindle
      cell subtype comprised all cases, with hyalinization and calcification in 57% of
      cases. The spindle cells were immunohistochemically positive for vimentin, CD117,
      and CD34. Twenty-four cases yielded sufficient DNA for subsequent molecular
      analysis, which showed c-KIT mutations in 11 cases (46%) and PDGFRA mutations in
      1 case (4%). Sporadic GIST tumorlets of the proximal stomach are common in the
      general population over the age of 50 years and frequently show somatic c-KIT
      mutations. GIST tumorlets probably represent the grossly recognizable counterpart
      of sporadic ICC hyperplasia caused by somatic c-KIT or PDGFRA mutations. Early
      hyalinization and calcification seems to confer limited growth potential, and
      complete regression of such lesions is common. GIST tumorlets likely represent
      preclinical (preneoplastic) lesions that need additional stimuli to evolve into
      clinical GISTs, raising the possibility of a hyperplasia-neoplasia sequence in
      the development of sporadic GISTs.

PMID- 17197928
TI  - BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based
      on morphology and molecular profiles from tissue microarrays.
AB  - A distinct morphologic and molecular phenotype has been reported for BRCA1
      associated breast cancers; however, the phenotype of BRCA2-associated breast
      cancers is less certain. To comprehensively characterize BRCA2-associated breast
      cancers we performed a retrospective case control study using tumors accrued
      through the Breast Cancer Family Registry. We examined the tumor morphology and
      hormone receptor status in 157 hereditary breast cancers with germline mutations
      in BRCA2 and 314 control tumors negative for BRCA1 and BRCA2 mutations that were
      matched for age and ethnicity. Tissue microarrays were constructed from 64 BRCA2
      associated and 185 control tumors. Tissue microarray sections were examined for
      HER2/neu protein overexpression, p53 status and the expression of basal markers,
      luminal markers, cyclin D1, bcl2, and MIB1 by immunohistochemistry. The majority
      of BRCA2-associated tumors and control tumors were invasive ductal, no special
      type tumors. In contrast to control tumors, BRCA2-associated cancers were more
      likely to be high grade (P<0.0001) and to have pushing tumor margins (P=0.0005).
      Adjusting for grade, BRCA2-associated tumors were more often estrogen receptor
      positive (P=0.008) and exhibited a luminal phenotype (P=0.003). They were less
      likely than controls to express the basal cytokeratin CK5 (P=0.03) or to
      overexpress HER2/neu protein (P=0.06). There was no difference in p53, bcl2,
      MIB1, or cyclin D1 expression between BRCA2-associated and control tumors. We
      have demonstrated, in the largest series of BRCA2-associated breast cancers
      studied to date, that these tumors are predominantly high-grade invasive ductal
      carcinomas of no special type and they demonstrate a luminal phenotype despite
      their high histologic grade.

PMID- 17197929
TI  - Extensive retraction artifact correlates with lymphatic invasion and nodal
      metastasis and predicts poor outcome in early stage breast carcinoma.
AB  - Retraction artifact resulting in clear spaces around tumor cell nests is
      frequently seen in histologic material and may present difficulty in their
      differentiation from lymphovascular invasion. We noticed that retraction artifact
      seemed to be more common around groups of breast cancer cells compared with
      benign acini, and when extensively present, metastasis to axillary lymph nodes
      was often seen. Thus, we performed a study of 304 cases of stage pT1 and pT2
      breast carcinomas to test our hypothesis that extensive retraction artifact in
      tumors correlates with lymphatic spread and outcome. Tumors were evaluated to
      determine the presence and extent of retraction artifact around tumor cell nests
      and the presence of lymphatic invasion. Lymphatic invasion was confirmed by D2-40
      immunostaining. The extent of retraction artifact in tumors was correlated with
      clinicopathologic tumor features and patient outcome. Variable degree of
      retraction artifact was present in 183 of 304 (60%) invasive carcinomas, with its
      extent ranging from 0% to 90% (median 5%). The extent of retraction artifact
      showed a significant correlation with tumor size, histologic type, histologic
      grade, presence of lymphovascular invasion, and nodal metastasis. Further,
      extensive retraction artifact was significantly associated with poor overall and
      disease-free survival in both univariate and multivariate analyses. We propose
      that the apparent retraction of the stroma from cells of invasive breast
      carcinoma on routine histologic sections is not a phenomenon merely due to
      inadequate fixation as currently believed. Rather, it likely signifies important
      biologic changes that alter tumor-stromal interactions and contribute to
      lymphatic spread and tumor progression.

PMID- 17197930
TI  - Globular amyloid deposits isolated to the small bowel: a rare association with AL
      amyloidosis.
AB  - We describe a 55-year-old man with isolated duodenal and jejunal amyloidosis
      producing rare endoscopic and histologic findings. The patient had no specific
      gastrointestinal complaints but underwent esophagogastroduodenoscopy and
      colonoscopy because of progressive microcytic anemia. Endoscopy revealed multiple
      polyps, some filiform and measuring up to 3 cm in length, in the duodenum and
      proximal jejunum. Microscopically, the polyps resulted from amyloid deposition,
      predominantly within the submucosa, but also focally involving muscularis mucosae
      and lamina propria. The amyloid formed multiple globular submucosal deposits with
      a lamellated appearance reminiscent of corpora amylacea; linear amyloid
      deposition was also present in a perivascular distribution and within the
      overlying mucosa. Immunophenotyping confirmed AL amyloidosis with lambda
      immunoglobulin light chain restriction. There was no clinical evidence of
      visceral amyloidosis. The source of lambda light chain production was unclear as
      bone marrow biopsy and multiple gastrointestinal biopsies revealed normal numbers
      of polyclonal plasma cells. Further, immunoglobulin-free light chain assay was
      normal, as were serum and urine protein electrophoreses with immunofixation. This
      endoscopic presentation of isolated small bowel polyposis is an uncommon
      association with AL amyloidosis and to our knowledge this represents the first
      case of globular gastrointestinal amyloidosis resulting from AL amyloid.

PMID- 17197931
TI  - Hepatoid carcinoma of the pancreas: a case report and literature review of a
      heterogeneous group of tumors.
AB  - Hepatoid carcinomas are tumors that display, at least focally, cytologic and/or
      architectural features of hepatocellular carcinoma. They have been described in
      several organs, most notably in the stomach and ovary. We report a case of
      hepatoid carcinoma of the pancreas that developed in a 41-year-old woman in
      association with a pancreatic endocrine carcinoma. The fine needle aspiration
      material was characterized by the presence of monotonous, small-to-medium sized
      tumor cells with round nuclei and finely granular chromatin, intermixed with more
      atypical tumor cells displaying larger nuclei with coarse clumped chromatin,
      prominent nucleoli, and moderate amounts of foamy cytoplasm. The excised specimen
      displayed a poorly differentiated pancreatic endocrine carcinoma associated with
      well-defined islands of larger tumor cells growing in a perisinusoidal pattern
      which, based on their immunohistochemical profile and the demonstration of bile,
      proved to represent a hepatoid component. This case and prior examples in the
      literature suggest that hepatoid carcinomas of the pancreas appear to be a
      heterogeneous group of tumors (pure or associated with another histologic
      component) that are often associated with early liver metastasis and a short
      survival, although those arising as a component of endocrine tumors seem to fare
      slightly better. Hepatoid carcinoma of the pancreas should be included in the
      differential diagnosis of pancreatic tumors composed of large eosinophilic cells.

PMID- 17197932
TI  - Ras protein expression and autophagic tumor cell death in neuroblastoma.

PMID- 17197934
TI  - Advances in Plastic Surgery: a long journey over 25 years.

PMID- 17197935
TI  - Reduction mammaplasty and sensitivity of the nipple-areola complex: sensuality
      versus sexuality?

PMID- 17197936
TI  - Reconstruction of total absence of the breast.

PMID- 17197937
TI  - Advances in autogenous breast reconstruction: the role of preoperative perforator
      mapping.

PMID- 17197938
TI  - Muscle perforator flaps.

PMID- 17197939
TI  - Oncoplastic approach to early breast cancer in women with macromastia.

PMID- 17197940
TI  - Automated facial image analysis: detecting improvement in abnormal facial
      movement after treatment with botulinum toxin A.
AB  - The purpose of this study was to evaluate the ability of Automated Facial Image
      Analysis (AFA) to detect changes in facial motion after Botox injections in
      patients with facial nerve disorders accompanied by abnormal muscle activity.
      Eight subjects received Botox for oral to ocular synkinesis (n = 6), ocular to
      oral synkinesis (n = 1), and/or depressor anguli oris overactivity (n = 3).
      Subjects were video-recorded during 2 directed facial action tasks before and
      after Botox treatment. AFA measurement and Facial Grading System (FGS) scores
      were used to evaluate the effects of Botox. After Botox, AFA detected a decrease
      in abnormal movements of the eyelids in all patients with oral to ocular
      synkinesis, a decrease in oral commissure movement for the patients with ocular
      to oral synkinesis, and an increase in oral commissure movement in all patients
      with depressor overactivity. The FGS scores failed to demonstrate any change in
      facial movement for the case of ocular to oral synkinesis and for 2 cases of
      depressor overactivity. AFA enables recognition of subtle changes in facial
      movement that may not be adequately measured by observer based ratings of facial
      function.

PMID- 17197941
TI  - Comparison of three methods for the estimation of total intracranial volume:
      stereologic, planimetric, and anthropometric approaches.
AB  - There is a well-known close relationship between the total intracranial volume
      (TIV) and the brain size. Several studies in different countries have estimated
      the cranial capacity, which indirectly reflects the brain volume. However, we
      have not seen a study evaluating the results of the methodologies for the
      assessment of TIV. This study was carried out on 30 normal subjects whose ages
      ranged between 19 and 77 years old (males, 18; females, 12). Three different
      methods were used to assess the TIV. The mean (+/-SD) estimated TIV using linear
      dimensions method in males and females were 1416.8 +/- 64 cm and 1291.9 +/- 152
      cm, respectively. The mean estimated TIV using point counting method in males and
      females was 1474 +/- 93 cm and 1252 +/- 72 cm, respectively. By using the
      planimetric method of the mean and SD of TIV, male and females were 1492.1 +/- 74
      cm and 1319.6 +/- 100 cm, respectively. There were no statistical difference
      between TIV measurements obtained using the optimized stereologic technique and
      planimetry (P > 0.05). TIV between males and females was statistically
      significant (P < 0.001). This study showed that there are minor differences among
      the given 3 distinct methods. With the disadvantage of requiring more time to
      apply, the planimetry and point counting methods provide more assumption-free
      results than the anthropometric approach. However, the anthropometric method can
      be applied to assess TIV without needing sophisticated tools.

PMID- 17197942
TI  - Completing the metamorphosis: building a center of excellence in postbariatric
      plastic surgery.
AB  - Postbariatric body contouring is an expanding and rapidly evolving specialty
      within plastic surgery. To best address the many clinical issues related to the
      safe and effective care of the postbariatric patient, the authors have
      established a dedicated multidisciplinary treatment center. Team building efforts
      have brought together attending plastic surgeons who specialize in body
      contouring, nurses focused on body contouring after weight loss, and an
      administrative staff well trained in the issues related to managing these
      specific types of cases. Through core partnerships, nutritionists, lifestyle
      counselors, and psychologic professionals are present in the clinic to evaluate
      patients alongside the plastic surgeon. A dedicated physician assistant and body
      contouring fellow work in both the clinic and the operating room (OR). This team
      approach has allowed for the establishment of defined screening procedures and
      patient care algorithms. Outreach and patient education initiatives have allowed
      the center to forge strong alliances with the regional bariatric surgeons and
      make patients aware of the role of plastic surgery as they start the process of
      weight loss. A strong research mission is demonstrated by an IRB-approved
      clinical registry and database that facilitate outcomes studies.

PMID- 17197943
TI  - Rigid external fixation and condylar remodeling.
AB  - Condylar fractures, instead of other mandibular fractures, play a primary
      importance role because their high incidence and the historic controversy
      existent in literature regarding their treatment. Recent studies prove that
      conservative treatment of condylar fractures, although not determining perfect
      alignment of the fractured segments, leads to a series of histologic and
      morphologic healing processes ending with consolidation of the fracture and
      functional recovery of the TMJ (temporo-mandibular joint). In this study, we
      observed long-term results of 2 cases of bicondylar fracture treated with
      surgical reduction and rigid external fixation. Rx orthopantomography control 1
      year after surgery showed condylar remodeling bilaterally with good functional
      recovery. Our school affirms that semirigid fixation system allows optimal
      function between the articular head and the glenoid fossa, with good
      tridimensional repositioning of the fractured segments.

PMID- 17197944
TI  - Immediate and delayed use of arteriovenous fistulae in microsurgical flap
      procedures: a clinical series and review of published cases.
AB  - In microsurgical flap procedures, creation of an arteriovenous fistula (AVF) is a
      technique of vein grafting where the vein graft is connected to recipient vessels
      as a flow-through loop prior to harvest and inset of the flap. Controversy exists
      whether this technique can be used as a 2-stage procedure with the loop and flap
      transfer accomplished in sequential operations or if the loop and flap transfer
      should be performed in a single operation. We performed 12 consecutive 1-stage
      AVF-flap procedures, with 1 flap failure. We combined this series with previously
      published reports to compare outcomes of 1-stage and 2-stage procedures. We found
      no significant difference in flap outcomes or complication rates between the 2
      strategies. We conclude from our experience and this analysis that single-stage
      AVF-flap procedures are the optimum application of this technique.

PMID- 17197945
TI  - Microsurgery in infrapopliteal revascularization of lower limb.

PMID- 17197946
TI  - Sprayed cultured epithelial autografts for deep dermal burns of the face and
      neck.
AB  - The objective of this study was the assessment of clinical results after sprayed
      application of cultured epithelial autograft (CEA) suspensions onto deep dermal
      burn wounds of the face and neck. Nineteen patients with deep dermal burns of the
      face and neck were included into a prospective study. The average total body
      surface area burn was 15.1% (7%-46%; median: 13%). The average Abbreviated Burn
      Severity Index (ABSI) was 6.7 points (4-12 points; median: 7 points). The
      application of sprayed CEA suspension was performed onto an average body surface
      area of 2% (0.5-5%; median: 2%). Thirteen patients were recruited for clinical
      follow-up after an average of 10 months (3-18 months). The average Vancouver Scar
      Scale score at follow-up was 2.4 +/- 2.2 points (range, 0-8 points), and the
      average Donnersmarck and Horbrand score was 9.3 +/- 6.8 points (range, 0-22).
      Four patients had less than 9 months' follow-up. Excluding these patients from
      the analysis resulted in an average Vancouver Scar Scale score of 1.3 +/- 0.9
      points (range, 0-3 points) and an average Donnersmarck and Horbrand score of 8.0
      +/- 7.4 points (range 0-22) for the remaining 9 patients.Our data show that
      enzymatic and careful surgical debridement and consecutive application of CEA
      suspensions using a spray technique results in excellent cosmetic outcomes
      compared with any other method.

PMID- 17197947
TI  - Reconstruction of the distal third of the nose with composite ear-helix free
      flap.
AB  - Full-thickness defects of the nose result in severe esthetic and functional
      problems. Regardless of the etiology of such defects, the complexity of the
      reconstruction process of full-thickness defects of this region is not correlated
      with the size of the defect. Local flaps are frequently used for reconstruction
      but often yielding facial scarring and bulky alae. Composite helical grafts are
      used for relatively small defects but defects of more than 2.0 cm in diameter
      require vascularized tissue transfer. Composite free flap from the root of the
      auricular helix has been used to reconstruct an anatomically diverse set of
      defects of the distal third of the nose, with satisfactory success in our series
      of 6 patients.

PMID- 17197948
TI  - Soft-tissue reconstruction of an open tibial wound in the distal third of the
      leg: a new treatment algorithm.
AB  - Over the past 4 years, a total of 33 patients, each with an open tibial wound in
      the distal third of the leg, underwent a skin-grafted muscle flap reconstruction
      according to the new treatment algorithm developed by the author. When the size
      of the soft-tissue defect was less than 50 cm, a pedicled medial hemisoleus
      muscle flap was used for the soft-tissue coverage (n = 20). If the soleus muscle
      was traumatized, a small free muscle flap (ie, gracilis) was then used (n = 3).
      When the size of the soft-tissue defect was greater than 50 cm, a larger free
      muscle flap (ie, rectus abdominis or latissimus dorsi) was selected (n = 10). All
      patients were followed for up to 4 years. Three patients with a medial hemisoleus
      muscle flap developed insignificant distal flap necrosis and were treated
      subsequently with debridement and flap advancement. Five patients with a free
      muscle flap required an additional operation, and 2 patients had a subsequent
      debulking procedure of the flap for contour improvement of the leg. Reliable soft
      tissue coverage with a well-healed tibial wound, evident fracture healing, and
      good contour of the leg were achieved in all 33 patients during follow-up.
      Following this new treatment algorithm, a selected option for an open tibial
      wound in the distal third of the leg can provide reliable soft-tissue coverage
      for different sizes of open tibial wounds and may offer a more cost-effective
      approach for managing such a complex clinical problem.

PMID- 17197949
TI  - Staged and late-period reconstruction of the crushed hand: prefabricated osseous
      flap.
AB  - The principle of controlled utilization of increased vascularity in the regions
      of artificially established ischemia constituted the basis of prefabrication of
      the vascular induction through staged transfers. We have used this principle, and
      a part of a metacarpal bone was prefabricated with an artery. The artery was
      inserted into the bone, and a defect was repaired with this prefabricated osseous
      flap; meanwhile, another defect was amended with a bone graft. The static bone
      scintigraphy of the hand at the 6-month postoperative stage indicated evident
      superiority of the vascularity of the prefabricated osseous flap at the ring
      finger when compared with the bone graft at the middle finger. The angiography
      demonstrated a high vascular pattern of the flap at its location at the proximal
      phalanx of the ring finger. The structures that remained healthy after the injury
      either on the amputated side or on the hand could be used in reconstruction. The
      tendinous and osseous structures could be used as free grafts, and the vascular
      structures could be transferred as vascular pedicles, allowing the creation of
      previously nonexistent flaps and composite tissues that were ideal for
      reconstruction. Any tissue possessing a vascular supply could be used as a
      vascular crane in any prefabrication process.

PMID- 17197950
TI  - Explantation of 41-year-old implants following primary breast augmentation.
AB  - The long-term affects of primary breast augmentation is a topic of controversy.
      This case report will highlight the long-term outcome in a woman with Ivalon
      sponge breast implants and the reasons for explantation. The focus of the
      manuscript will include mammography, capsular contracture, and late hematoma.

PMID- 17197951
TI  - Repair of the abdominal donor-site fascial defect with small intestinal submucosa
      (Surgisis) after TRAM flap breast reconstruction.
AB  - We report the successful use of Surgisis in the repair of the abdominal donor
      site fascial defect following a free transverse rectus abdominis myocutaneous
      (TRAM) flap breast reconstruction. No abdominal wall weakness in the flap donor
      site was evidenced by a series of clinical examinations to at least 14 months
      after Surgisis placement. A well-formed and thickened fascial layer at the
      abdominal donor fascial repair site was revealed by computed tomography scan.
      This objective finding, along with our clinical observation, supports the use of
      Surgisis for repair of the abdominal donor site fascial defect following a TRAM
      flap harvesting.

PMID- 17197952
TI  - Immediate breast reconstruction (IBR) with direct, anatomic, extra-projection
      prosthesis: 102 cases.
AB  - There are different methods described until now for immediate breast
      reconstruction. Despite the use of autologous flaps considered by many authors,
      implants are considered as an option by others. A prospective study of 102
      clinical cases was designed, including a 1-year follow-up in which glands were
      reconstructed by immediate breast reconstruction (IBR) with direct, extra
      projection, anatomic prostheses located in a submuscular pocket after a skin
      sparing mastectomy. The prosthesis coverage was made by the muscle in its upper
      two thirds and by using the skin from the mastectomy in its lower third. The
      cosmetic results obtained were evaluated according to the volume, form, and
      symmetry achieved using a linear numeric analogical score. This evaluation had an
      averaged value of 2.79 +/- 0.8 in our scale from poor (0) to excellent result
      (4). The overall rate of complications was 15.7% of the cases, with seroma being
      the most frequent. In conclusion, this preliminary study demonstrates that
      immediate breast reconstruction with a direct, extra projection, anatomic
      prosthesis is a good alternative. Nevertheless, more long-term studies with a
      higher number of patients and using an SF-36 for patient satisfaction are needed
      to confirm these results.

PMID- 17197953
TI  - A safe and effective way for reduction of temporomandibular joint dislocation.
AB  - Anterior dislocation of the temporomandibular joint (TMJ) is a common problem
      which demands immediate reduction to relieve the discomfort. The most popular
      technique is to put the operator's thumbs over the molar teeth of the patient and
      push the dislocated jaw downward and backward. This maneuver takes a lot of
      effort and usually needs sedation. Failure to reduction is not uncommon.
      Furthermore, the physician has to take the risk of being bitten and disease
      transmission. A novel method for reduction of the dislocated TMJ via extraoral
      route is presented, based on the observation that once the mandible is dislocated
      anteriorly, the coronoid process and anterior border of the ramus can be palpated
      easily over the cheek. By applying steady pressure over this prominent part, the
      anteriorly dislocated mandible can be reduced easily. From May 2000 to July 2005,
      there were 7 anterior mandible dislocations treated successfully by this method
      in Chang Gung Memorial Hospital. None of the patients need any adjuvant
      medication for sedation or relaxation. This technique is simple and effective,
      and the physicians are spared from the risk of bite trauma and unexpected disease
      transmission.

PMID- 17197954
TI  - Optimization of microsurgery: improved coverage of the latissimus dorsi vascular
      pedicle with vascularized serratus fascia.
AB  - The latissimus dorsi free flap is a workhorse for extremity reconstruction. One
      of its benefits is a long vascular pedicle that spans the zone of injury.
      However, it may be difficult to adequately cover this pedicle. Direct closure may
      be too tight, and skin grafting over the pedicle risks exposure if graft take is
      poor. We report a technique in which the serratus branch of the thoracodorsal
      artery and its overlying fascia are harvested en bloc with the thoracodorsal
      artery and latissimus muscle. This provides 2 flaps on a common pedicle that can
      easily be rotated to allow positioning and insetting. We successfully used this
      technique in the reconstruction of both upper and lower extremities. The serratus
      fascia provides excellent padded covering and is a good bed for skin grafting.
      The versatility of this hybrid flap will allow its use in a range of complex
      reconstructive procedures.

PMID- 17197955
TI  - A novel hook plate fixation technique for the treatment of mallet fractures.
AB  - Bony mallet injuries are generally treated nonoperatively, but when the fragment
      involves a significant percentage of the articular surface, articular incongruity
      and instability can occur. A number of techniques have been described for the
      fixation of such fractures and each has its own problems. Anatomic reduction and
      secure fixation of small fragments can be challenging. Our objective is to
      describe a new surgical technique using a 1.3-mm hook plate that provides good
      reduction and stable fixation of a mallet fracture, with early mobilization of
      the distal interphalangeal joint.

PMID- 17197956
TI  - Delayed extended "midthenar" flap for reconstruction of total fingertip avulsion
      injury and a proposal of ideal postoperative immobilization for a palmar flap.
AB  - Avulsion injury through the base of the distal phalanx of the ring finger with a
      large projecting tip of exposed bone was treated with delayed extended midthenar
      flap. The midthenar flap adding delay procedure at the first stage of a
      consecutive 2-stage operation could provide extended flap length to wrap the
      large projecting tip of the exposed bone at the second stage. This flap is useful
      for the middle and ring fingertip injury because motions of the all thumb joints
      are not restricted during the immobilization period. To reduce immobilization
      discomfort between the 2 stages of the palmar flap operation, a "relaxed flexion
      position" immobilization technique devised by the authors is also introduced.

PMID- 17197957
TI  - Impact of laparoscopic resection for colorectal cancer on operative outcomes and
      survival.
AB  - OBJECTIVE: This study aimed to compare the outcomes of patients who underwent
      laparoscopic and open resections for colorectal cancer. Comparison of colectomy
      in 2 consecutive periods (period 1: January 1996-May 2000; period 2: June 2000
      December 2004), with laparoscopic surgery being a surgical option in period 2,
      was also performed. SUMMARY BACKGROUND DATA: Prospective data of 1134 patients
      (448 in period 1; 656 in period 2) who underwent elective resection for colon and
      upper rectal cancer (above 12 cm from anal verge) were analyzed. METHODS: The
      operative outcome and survival were compared between patients who underwent
      laparoscopic and open resection in period 2. The outcomes of colorectal
      resections in the 2 periods were also compared. RESULTS: During period 2, the
      operative mortality rates of patients with laparoscopic (n = 401) and open
      resection (n = 255) were 0.8% and 3.7%, respectively (P = 0.022), and the
      morbidity rates were 21.7% and 15.7%, respectively (P = 0.068). The patients who
      underwent laparoscopic resection had significantly earlier return of bowel
      function, earlier resumption of diet, and shorter hospital stay. The 3-year
      overall survivals in those with nondisseminated disease were 74.4% and 78.8% for
      open and laparoscopic resection, respectively (P = 0.046). The operative morality
      rates were 4.4% and 2.6% in period 1 and period 2, respectively (P = 0.132). The
      3-year overall survivals for patients with nondisseminated disease were 69.7% and
      76.1% for period 1 and period 2, respectively (P = 0.019). The overall survivals
      in patients who underwent open resection in the 2 periods were similar (P =
      0.284). CONCLUSIONS: The short-term favorable outcome of laparoscopic resection
      for colorectal cancer was confirmed and improvement of survival was observed with
      the practice of laparoscopic resection.

PMID- 17197958
TI  - Laparoscopic colectomy for cancer: the tale of two studies.

PMID- 17197959
TI  - Early endoscopic intervention versus early conservative management in patients
      with acute gallstone pancreatitis and biliopancreatic obstruction: a randomized
      clinical trial.
AB  - OBJECTIVE: To test the hypothesis that early endoscopic intervention, performed
      on patients with acute gallstone pancreatitis and biliopancreatic obstruction,
      reduces systemic and local inflammation. SUMMARY BACKGROUND DATA: The role of
      early endoscopic intervention, in the treatment of acute gallstone pancreatitis,
      remains controversial. Previous randomized trials have not focused on the
      subgroup of patients with clinical evidence of biliopancreatic obstruction.
      METHODS: This single-center randomized clinical trial was performed between May
      2000 and September 2005. Of 238 patients, admitted within 48 hours after the
      onset of acute gallstone pancreatitis, 103 with a distal bile duct measuring > or
      =8 mm combined with a total serum bilirubin > or =1.20 mg/dL, were randomized to
      receive either endoscopic retrograde cholangiopancreatography followed by
      endoscopic papillotomy for bile duct stones (EEI, n = 51) or early conservative
      management (ECM, n = 52). Patients with clinical evidence of coexisting acute
      cholangitis were excluded. Outcome measures included changes in organ failure
      score and computed tomography (CT) severity index during the first week after
      admission, incidence of local complications, and overall morbidity and mortality.
      RESULTS: The incidence of bile duct stones at EEI was 72% and 40% of patients in
      the ECM group had persisting bile duct stones at elective biliary surgery. No
      significant differences were found between the EEI and ECM groups regarding
      changes in mean organ failure score (P = 0.87), mean CT severity index (P =
      0.88), incidence of local complications (6% vs. 6%, P = 0.99), overall morbidity
      (21% vs. 18%, P = 0.80), and mortality (6% vs. 2%, P = 1). CONCLUSIONS: The
      present study failed to provide evidence that early endoscopic intervention
      reduces systemic and local inflammation in patients with acute gallstone
      pancreatitis and biliopancreatic obstruction. If acute cholangitis can be safely
      excluded, early endoscopic intervention is not mandatory and should not be
      considered a standard indication.

PMID- 17197960
TI  - Early management of acute gallstone pancreatitis.

PMID- 17197961
TI  - Steatosis as a risk factor in liver surgery.
AB  - OBJECTIVE: To review present knowledge of the influence of hepatic steatosis in
      liver surgery as derived from experimental and clinical studies. SUMMARY
      BACKGROUND DATA: Hepatic steatosis is the most common chronic liver disease in
      the Western world, and it is associated with obesity, diabetes, and metabolic
      syndrome. Fatty accumulation affects hepatocyte homeostasis and potentially
      impairs recovery of steatotic livers after resection. This is reflected
      clinically in increased mortality and morbidity after liver resection in patients
      with any grade of steatosis. Because of the epidemic increase of obesity, hepatic
      steatosis will play an even more significant role in liver surgery. METHODS: A
      literature review was performed using MEDLINE and key words related to
      experimental and clinical studies concerning steatosis. RESULTS: Experimental
      studies show the increased vulnerability of steatotic livers to various insults,
      attributed to underlying metabolic and pathologic derangements induced by fatty
      accumulation. In clinical studies, the severity of steatosis has an important
      impact on patient outcome and mortality. Even the mildest form of steatosis
      increases the risk of postoperative complications. CONCLUSIONS: Hepatic steatosis
      is a major factor determining patient outcome after surgery. Further research is
      needed to clarify the clinical relevance of all forms and severity grades of
      steatosis for patient outcome. Standardized grading and diagnostic methods need
      to be used in future clinical trials to be able to compare outcomes of different
      studies.

PMID- 17197962
TI  - Two hundred liver hanging maneuvers for major hepatectomy: a single-center
      experience.
AB  - OBJECTIVE: To establish the indications of the liver hanging maneuver for major
      hepatectomy. SUMMARY BACKGROUND DATA: The liver hanging maneuver, which is a
      technique of passing a tape along the retrohepatic avascular space and suspending
      the liver during parenchymal transection, facilitates anterior approach of major
      hepatectomy. However, the feasibility and limits of this maneuver have never been
      established in patients with different clinical backgrounds. METHODS: Medical
      records of 242 consecutive patients considered for major hepatectomy using the
      hanging maneuver were reviewed. RESULTS: Among 242 patients, 14 patients (6%)
      were considered to have contraindication for this maneuver preoperatively because
      of tumor infiltration to anterior surface of retrohepatic inferior vena cava
      (IVC). It was successful in 201 patients with overall feasibility of 88%. The
      feasibility increased significantly in the recent years as compared with the
      initial years (94% in 2003-2005 vs. 76% in 2000-2002, P < 0.0001). Bleeding
      during the retrohepatic dissection occurred in 5 patients (2%), which was minor
      due to injury of hepatic capsule in 3 (1%) and major due to injury of short
      hepatic vein in 2 (1%). In all cases, bleeding stopped spontaneously. The
      maneuver was abandoned in 27 patients, including 15 related to severe adhesion
      between liver and IVC. Univariate analysis showed that adhesion between IVC and
      liver was the only significant negative predictor affecting the feasibility.
      Cirrhosis, large tumor, preoperative radiologic treatments did not influence on
      the feasibility. CONCLUSIONS: The liver hanging maneuver has 94% feasibility in
      recent years. Absolute contraindication is tumor infiltration to the retrohepatic
      avascular space. Adhesion between the IVC and liver has a negative impact of the
      feasibility. According to this indication, the hanging maneuver is easily
      achievable without risk of the major bleeding during the retrohepatic dissection.

PMID- 17197963
TI  - Partial hepatectomy with wide versus narrow resection margin for solitary
      hepatocellular carcinoma: a prospective randomized trial.
AB  - OBJECTIVE: To compare the efficacy and safety of partial hepatectomy aiming
      grossly at a narrow (1 cm) and a wide (2 cm) resection margin in patients with
      macroscopically solitary hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA:
      For HCC treated with partial hepatectomy, the extent of the margin of liver
      resection remains controversial despite extensive studies. METHODS: We conducted
      a prospective randomized trial in patients with solitary HCC. From January 1999
      to February 2003, 169 patients with solitary HCC were stratified according to
      tumor size and randomized to undergo partial hepatectomy aiming grossly at either
      a narrow (1 cm) (n = 84) or a wide resection margin (2 cm) (n = 85). Analyses
      were done on an intention-to-treat basis. RESULTS: The demographic and pathologic
      data were similar in the 2 groups. The mean +/- SD for the final resection margin
      of the narrow and the wide margin groups were 0.7 +/- 0.4 cm and 1.9 +/- 0.6 cm,
      respectively. There was no significant difference in the morbidity and in
      hospital mortality between the 2 groups of patients. The 1-, 2-, 3-, and 5-year
      overall survival rates for the narrow and the wide margin groups were 92.9%,
      83.3%, 70.9%, and 49.1% and 96.5%, 91.8%, 86.9%, and 74.9%, respectively. The
      difference was significant (stratified log-rank test, P = 0.008). Multivariate
      analysis identified the presence of micrometastases and the treatment allocation
      were independent risk factors for tumor-related death. At the time of censor, 75
      (44.4%) patients had developed tumor recurrence. All recurrences at the margins
      of liver resection were observed in the narrow margin group. Multiple tumor
      recurrence was also significantly higher in the narrow margin group (chi test, P
      = 0.018). Survival after tumor recurrence was significantly better in the wide
      margin group than the narrow margin group (log-rank test, P = 0.017). CONCLUSION:
      For macroscopically solitary HCC, a resection margin aiming grossly at 2 cm
      efficaciously and safely decreased postoperative recurrence rate and improved
      survival outcomes when compared with a gross resection margin aiming at 1 cm,
      especially for HCC < or =2 cm.

PMID- 17197964
TI  - Severe steatosis increases hepatocellular injury and impairs liver regeneration
      in a rat model of partial hepatectomy.
AB  - OBJECTIVE: The aim of this study was to assess the influence of severe steatosis
      with inflammation on hepatocellular recovery after 70% hepatectomy in a rat model
      of diet-induced steatosis. BACKGROUND: Patients with steatosis have an increased
      risk of inflammatory complications after liver resection. This might be
      attributable to Kupffer cell-mediated inflammation in steatotic livers causing
      progressive injury. METHODS: Male Wistar rats were fed a standard methionine- and
      choline-deficient diet for 1 or 5 weeks. A 70% partial hepatectomy (PH) was
      performed, after which rats were killed at 24, 48, or 72 hours. The extent of
      steatosis and inflammation was determined by assessment of hepatic triglycerides,
      cytokine content, and histopathology. Outcome parameters were: liver regeneration
      (MIB-5 proliferation rate, mitotic index, and regenerating liver mass),
      hepatocellular injury (plasma aminotransferases, lipid peroxidation,
      histopathology, and apoptosis), Kupffer cell-mediated proinflammatory response
      (TNF-alpha, IL-1beta, IL-6, IL-10 in plasma and liver) and antioxidant content
      (total glutathione). RESULTS: Methionine- and choline-deficient diet induced
      uncomplicated steatosis after 1 week (<30% hepatocytes affected without
      inflammation) and severe steatosis after 5 weeks (>60% hepatocytes affected,
      including prominent inflammation) as confirmed by histopathology. After PH, liver
      regeneration was impaired at all time points in the severe steatosis group as
      compared with the mild and control groups (P < 0.05). Hepatocellular injury was
      significantly increased in the severe steatosis group at all time points (P <
      0.05). Kupffer cell-mediated inflammatory responses were aggravated in the severe
      steatosis group along with decreased antioxidant content (P < 0.05). Necrosis was
      the main type of cell death in severe steatotic livers compared with mainly
      apoptotic cell death in mild steatotic and normal livers. CONCLUSION: Steatosis
      with prominent inflammation impaired liver regeneration probably because of
      increased hepatocellular lipid peroxidation and damage in concert with Kupffer
      cell-mediated proinflammatory responses. These results suggest an increased risk
      of performing extensive liver resection in the presence of severe steatosis.

PMID- 17197965
TI  - Difference in tumor invasiveness in cirrhotic patients with hepatocellular
      carcinoma fulfilling the Milan criteria treated by resection and transplantation:
      impact on long-term survival.
AB  - SUMMARY BACKGROUND DATA: Some previous studies demonstrated better survival after
      transplantation for small hepatocellular carcinoma (HCC) compared with resection,
      but the influence of differences in tumor invasiveness between transplanted and
      resected patients has not been studied. This study compared the tumor
      characteristics of patients with HCC within the Milan criteria treated by
      resection or transplantation, and elucidated their impact on long-term survival.
      PATIENTS AND METHODS: Tumor characteristics and long-term survival of 204
      cirrhotic patients with resection and 43 cirrhotic patients with transplantation
      for HCC within the Milan criteria were compared. A multivariate analysis was
      performed to determine the prognostic factors of survival in all patients with
      resection or transplantation. RESULTS: Tumors in the transplanted group were
      associated with lower incidence of high-grade tumors, microscopic venous
      invasion, and microsatellite nodules. The overall 5-year survival was better in
      the transplantation group than the resection group (81% vs. 68%, P = 0.017).
      However, there were no significant differences in survival between the two groups
      when stratified according to presence or absence of venous invasion. Multivariate
      analysis showed that hepatitis C virus serology, tumor size, tumor number, and
      microscopic venous invasion, but not resection or transplantation, were of
      prognostic significance. CONCLUSIONS: There were significant differences in tumor
      invasiveness in HCC treated by transplantation and resection as a result of
      selection bias, even in patients with the tumors fulfilling the Milan criteria.
      When the different tumor invasiveness was taken into account, there was no
      significant difference in the long-term survival after resection or
      transplantation.

PMID- 17197966
TI  - Predictors of patient selection in bariatric surgery.
AB  - OBJECTIVE: To identify sociodemographic and clinical predictors of patient
      selection in bariatric surgery. SUMMARY BACKGROUND DATA: Population-based studies
      suggest that bariatric surgery patients are disproportionately privately insured,
      middle-aged white women. It is uncertain whether such disparities are due to
      surgeon decisions to operate, differences among morbidly obese individuals in
      access to surgery, or patients' personal preferences regarding surgical
      treatment. METHODS: We conducted a national survey of 1343 U.S. bariatric
      surgeons. The questionnaire contained clinical vignettes generated using a
      balanced fractional factorial design. For each of 3 hypothetical patients unique
      in age, race, gender, body mass index (BMI), comorbidities, social support,
      functional status, and insurance, respondents were asked if they would operate.
      Logistic regression was used to determine the odds of selection for each
      characteristic while controlling for the other 7 characteristics. Subset analyses
      were also performed using combinations of BMI and comorbidities. RESULTS: A total
      of 62.5% of eligible surgeons responded (n = 820). Patient race did not influence
      surgeon decisions to operate. Hypothetical patient age, BMI, and social support
      were most influential. In the subgroup of patients who did not meet current NIH
      BMI and comorbidity criteria for bariatric surgery, male sex (odds ratio [OR],
      0.33; 95% confidence interval [CI], 0.14-0.76) was associated with decreased odds
      of selection. Overall, younger age (OR, 0.09; 95% CI, 0.07-0.11), older age (OR,
      0.70; 95% CI, 0.56-0.90), limited functional status (OR, 0.66; 95% CI, 0.52
      0.82), poor social support (OR, 0.37; 95% CI, 0.30-0.47), self-pay (OR, 0.72; 95%
      CI, 0.57-0.91), and public insurance (OR, 0.54; 95% CI, 0.43-0.67) were
      associated with decreased odds of selection. BMI and comorbidity criteria
      influenced the magnitude of these effects. CONCLUSIONS: Patient race did not play
      a role in surgeon decisions to operate. Further research should examine the roles
      of unequal access to bariatric surgery and differing socio-cultural perceptions
      of morbid obesity on racial disparities. The influence of patient age, gender,
      insurance status, social support, and functional status on decisions to operate
      was mitigated by BMI and comorbidities. Policy-makers currently debating BMI and
      comorbidity criteria for bariatric surgery should also consider guidelines
      pertaining to these sociodemographic issues that influence patient selection in
      bariatric surgery.

PMID- 17197967
TI  - A multicenter study on oncologic outcome of laparoscopic gastrectomy for early
      cancer in Japan.
AB  - BACKGROUND: Laparoscopic surgery for gastric cancer is technically feasible, but
      it is not widely accepted because it has not been evaluated from the standpoint
      of oncologic outcome. We conducted a retrospective, multicenter study of a large
      series of patients in Japan to evaluate the short- and long-term outcomes of
      laparoscopic gastrectomy for early gastric cancer (EGC). METHODS: The study group
      comprised 1294 patients who underwent laparoscopic gastrectomy during the period
      April 1994 through December 2003 in 16 participating surgical units (Japanese
      Laparoscopic Surgery Study Group). The short- and long-term outcomes of these
      patients were examined. RESULTS: Distal gastrectomy was performed in 1185
      patients (91.5%), proximal gastrectomy in 54 (4.2%), and total gastrectomy in 55
      (4.3%); all were performed laparoscopically. The morbidity and mortality rates
      associated with these operations were 14.8% and 0%, respectively. Histologically,
      1212 patients (93.7%) had stage IA disease, 75 (5.8%) had stage IB disease, and 7
      (0.5%) had stage II disease (the UICC staging). Cancer recurred in only 6 (0.6%)
      of 1294 patients treated curatively (median follow-up, 36 months; range, 13-113
      months). The 5-year disease-free survival rate was 99.8% for stage IA disease,
      98.7% for stage IB disease, and 85.7% for stage II disease. CONCLUSIONS: Although
      our findings may be considered preliminary, our data indicate that laparoscopic
      surgery for EGC yields good short- and long-term oncologic outcomes.

PMID- 17197968
TI  - Reoperation as a quality indicator in colorectal surgery: a population-based
      analysis.
AB  - OBJECTIVE: To describe unplanned procedures following colorectal cancer surgery
      that might be used as intermediate outcome measures, and to determine their
      association with mortality and length of stay. SUMMARY BACKGROUND: Variation in
      the quality of surgical care, especially for common illnesses like colorectal
      cancer, has received increasing attention. Nonfatal complications resulting in
      procedural interventions are likely to play a role in poor outcomes but have not
      been well explored. METHODS: Cohort analysis of 26,638 stage I to III colorectal
      cancer patients in the 1992 to 1996 SEER-Medicare database. INDEPENDENT
      VARIABLES: sociodemographics, tumor characteristics, comorbidity, and acuity.
      PRIMARY OUTCOME: postoperative procedural intervention. ANALYSIS: Logistic
      regression identified patient characteristics predicting postoperative procedures
      and the adjusted risk of 30-day mortality and prolonged hospitalization among
      patients with postoperative procedures. RESULTS: A total of 5.8% of patients
      required postoperative intervention. Patient characteristics had little impact on
      the frequency of postoperative procedures, except for acute medical conditions,
      including bowel perforation (relative risk [RR] = 3.0, 95% confidence interval
      [CI] = 2.5-3.6), obstruction (RR = 1.6; 95% CI = 1.4-1.8), and emergent admission
      (RR = 1.3; 95% CI = 1.1-1.4). After a postoperative procedure, patients were more
      likely to experience early mortality (RR = 2.4; 95% CI = 2.1-2.9) and prolonged
      hospitalization (RR = 2.2; 95% CI = 2.1-2.4). The most common interventions were
      performed for abdominal infection (31.7%; RR mortality = 2.9; 95% CI = 2.3-3.7),
      wound complications (21.1%; RR mortality = 0.7; 95% CI = 0.4-1.3), and organ
      injury (18.7%; RR mortality = 1.6; 95% CI = 1.1-2.3). CONCLUSIONS: Postoperative
      complications requiring additional procedures among colorectal cancer patients
      correlate with established measures of surgical quality. Prospective tracking of
      postoperative procedures as complication markers may facilitate outcome studies
      and quality improvement programs.

PMID- 17197969
TI  - Potential prognostic benefit of lateral pelvic node dissection for rectal cancer
      located below the peritoneal reflection.
AB  - OBJECTIVE: To identify the parameters related to the effective selection of
      patients who could receive prognostic benefit from lateral pelvic node
      dissection. BACKGROUND: Accurate preoperative diagnosis of lateral nodal
      involvement (LNI) remains difficult, and the indications for lateral lymph node
      dissection have been controversial. PATIENTS AND METHODS: A total of 244
      consecutive patients who underwent potentially curative surgery with lateral
      dissection for advanced lower rectal cancer (1985-2000) were reviewed. Patients
      were stratified into groups based on various parameters, and the therapeutic
      value index for survival benefit was compared among groups. The therapeutic index
      of lateral dissection was calculated by multiplying the frequency of metastasis
      to the lateral area and the cancer-related 5-year survival rate of patients with
      metastasis to the lateral area, irrespective of metastasis to other areas
      (mesorectal, superior rectal artery [SRA], and inferior mesenteric artery [IMA]
      areas). RESULTS: LNI was observed in 41 patients (17%); and 88% of them had nodal
      involvement in the region along the internal iliac/pudendal artery or in the
      obturator region ("vulnerable field"). The cancer-related 5-year survival rate
      among the patients with LNI was 42%; the therapeutic index for lateral dissection
      was calculated as 7.0 patients, which was much higher than that of
      lymphadenectomy of the SRA area (1.6 patients) and the IMA area (0.4 patients),
      and almost comparable to that of lymphadenectomy of the upward mesorectal area
      (6.9 patients). Although it was possible to select groups at high and low risk
      for LNI based on several parameters related to tumor aggressiveness, such as
      tumor differentiation in biopsy specimens, the therapeutic value index was not
      significantly different between these groups. Unlike these parameters, the
      diameter of the largest lymph node in the "vulnerable field," which was
      positively correlated with the rate of LNI but irrelevant to the prognosis, was
      able to successfully stratify patients by therapeutic index. CONCLUSIONS:
      Advanced lower rectal cancer patients having LNI in the lateral pelvic area are
      likely to receive prognostic benefit from lymphadenectomy. The most efficient
      means of determining the effectiveness of lateral dissection preoperatively is to
      estimate the nodal diameter in the "vulnerable" lateral regions by diagnostic
      imaging.

PMID- 17197970
TI  - A prospective pathologic analysis using whole-mount sections of rectal cancer
      following preoperative combined modality therapy: implications for sphincter
      preservation.
AB  - OBJECTIVE: The aims of this study were to use a comprehensive whole-mount
      pathologic analysis to characterize microscopic patterns of residual disease, as
      well as circumferential and distal resection margins, in rectal cancer treated
      with preoperative CMT; and to identify clinicopathologic factors associated with
      residual disease. SUMMARY BACKGROUND DATA: Recent studies have shown that
      preoperative combined modality therapy (CMT) for rectal cancer enhances rates of
      sphincter preservation. However, the efficacy of preoperative CMT in conjunction
      with a total mesorectal excision (TME)-based resection, in terms of resection
      margins using whole-mount sections, has not been reported. Furthermore, since
      patterns of residual disease and extent of distal spread following preoperative
      CMT are largely unknown, intraoperative determination of distal rectal
      transection remains a surgical challenge. METHODS: We prospectively accrued 109
      patients with endorectal ultrasound (ERUS)-staged, locally advanced rectal cancer
      (T2-T4 and/or N1), located a median distance of 7 cm from the anal verge,
      requiring preoperative CMT, and undergoing a TME-based resection. Comprehensive
      whole-mount pathologic analysis was performed, with particular emphasis on extent
      of residual disease, margin status, and intramural tumor extension.
      Clinicopathologic factors associated with residual disease were identified.
      RESULTS: A sphincter-preserving resection was feasible in 87 patients (80%), and
      in all 109 patients, distal margins were negative (median, 2.1 cm; range, 0.4-10
      cm). Intramural extension beyond the gross mucosal edge of residual tumor was
      observed in only 2 patients (1.8%), both < or =0.95 cm. There were no positive
      circumferential margins (median, 10 mm; range, 1-28 mm), although 6 were less
      than or equal to 1 mm. On multivariate analysis, residual disease was observed
      more frequently in distally located tumors (distance from anal verge <5 cm) (P =
      0.03). CONCLUSION: Our comprehensive pathologic analysis suggests that, following
      preoperative CMT and a TME-based resection, distal margins of 1 cm may provide
      for complete removal of locally advanced rectal cancer. Although residual cancer
      following preoperative CMT was more likely in the setting of distally located
      tumors, occult tumor beneath the mucosal edge was rare and, when present, limited
      to less than 1 cm. Our results extend the indications for sphincter preservation,
      as distal resection margins of only 1 cm may be acceptable for rectal cancer
      treated with preoperative CMT.

PMID- 17197971
TI  - Operative strategies for diverticular peritonitis: a decision analysis between
      primary resection and anastomosis versus Hartmann's procedures.
AB  - OBJECTIVE: To compare primary resection and anastomosis (PRA) with and without
      defunctioning stoma to Hartmann's procedure (HP) as the optimal operative
      strategy for patients presenting with Hinchey stage III-IV, perforated
      diverticulitis. SUMMARY BACKGROUND DATA: The choice of operation for perforated
      diverticulitis lies between HP and PRA. Postoperative mortality and morbidity can
      be high, and the long-term consequences life-altering, with no established
      criteria guiding clinicians towards selecting a particular procedure. METHODS:
      Probability estimates for 6879 patients with Hinchey III-IV perforated
      diverticulitis were obtained from two databases (n = 204), supplemented by expert
      opinion and summary data from 12 studies (n = 6675) published between 1980 and
      2005. The primary outcome was quality-adjusted life-years (QALYs) gained from
      each strategy. Factors considered were the risk of permanent stoma, morbidity,
      and mortality from the primary or reversal operations. Decision analysis from the
      patient's perspective was used to calculate the optimal operative strategy and
      sensitivity analysis performed. RESULTS: A total of 135 PRA, 126 primary
      anastomoses with defunctioning stoma (PADS), and 6619 Hartmann's procedures (HP)
      were considered. The probability of morbidity and mortality was 55% and 30% for
      PRA, 40% and 25% for PADS, and 35% and 20% for HP, respectively. Stomas remained
      permanent in 27% of HP and in 8% of PADS. Analysis revealed the optimal strategy
      to be PADS with 9.98 QALYs, compared with 9.44 QALYs after HP and 9.02 QALYs
      after PRA. Complications after PRA reduced patients QALYs to a baseline of 2.713.
      Patients with postoperative complications during both primary and reversal
      operations for PADS and HP had QALYs of 0.366 and 0.325, respectively. HP became
      the optimal strategy only when risk of complications after PRA and PADS reached
      50% and 44%, respectively. CONCLUSION: Primary anastomosis with defunctioning
      stoma may be the optimal strategy for selected patients with diverticular
      peritonitis as may represent a good compromise between postoperative adverse
      events, long-term quality of life and risk of permanent stoma. HP may be reserved
      for patients with risk of complications >40% to 50% after consideration of long
      term implications.

PMID- 17197972
TI  - Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive
      surgery and hyperthermic intraperitoneal chemotherapy.
AB  - OBJECTIVE: To evaluate the survival of patients with pseudomyxoma peritonei (PMP)
      treated by cytoreductive surgery and intraoperative hyperthermic intraperitoneal
      chemotherapy (HIPEC), and to identify factors with prognostic value. SUMMARY
      BACKGROUND DATA: PMP is a clinical syndrome characterized by progressive
      intraperitoneal accumulation of mucous and mucinous implants, usually derived
      from a ruptured mucinous neoplasm of the appendix. Survival is dominated by
      pathology. METHODS: A total of 103 patients (34 men and 69 women) treated at The
      Netherlands Cancer Institute between 1996 and 2004 were identified. Survival was
      calculated from date of initial treatment and corrected for a second procedure.
      PMP was pathologically categorized into disseminated peritoneal adenomucinosis
      (DPAM), peritoneal mucinous carcinomatosis (PMCA), and an intermediate subtype
      (PMCA-I). Clinical and pathologic factors were analyzed to identify their
      prognostic value for survival. RESULTS: Median follow-up was 51.5 months (range,
      0.1-99.5 months). Recurrence developed in 44%. A second procedure for recurrence
      was performed in 11 patients. The median disease-free interval was 25.6 months
      (95% confidence interval [CI], 14.8-43.6 months). The 3-year and 5-year disease
      free survival probability was 43.6% (95% CI, 34.4%-55.2%) and 37.4% (95% CI,
      28.2%-49.5%), respectively. The disease-specific 3-year and 5-year survival
      probability was 70.9% (95% CI, 62.0%-81.2%) and 59.5% (95% CI 48.7%-72.5%),
      respectively. Factors associated with survival were pathological subtype,
      completeness of cytoreduction, and degree and location of tumor load (P < 0.05).
      The main prognostic factor, independently associated with survival, was the
      pathologic subtype (P < 0.01). CONCLUSION: Cytoreductive surgery in combination
      with intraoperative HIPEC is a feasible treatment strategy for PMP in terms of
      survival. The pathologic subtype remains the dominant factor in survival.
      Patients should be centralized to improve survival by a combination of surgical
      experience and adequate patient selection.

PMID- 17197973
TI  - Toward current standards of donor right hepatectomy for adult-to-adult live donor
      liver transplantation through the experience of 200 cases.
AB  - OBJECTIVE: To define the current standards of donor right hepatectomy, including
      the middle hepatic vein for adult-to-adult live donor liver transplantation.
      SUMMARY BACKGROUND DATA: Donor morbidity and mortality are inevitable given the
      ultra-major nature of the donor operation. Results from a matured center could
      define the true impact of this donor procedure most accurately. PATIENTS AND
      METHODS: From May 9, 1996 to April 13, 2005, 200 consecutive donors underwent
      donor right hepatectomy at the University of Hong Kong Medical Center. All right
      liver grafts except one included the middle hepatic vein. Donor characteristics,
      operation time, blood loss, hospital stay, laboratory results, and complications
      graded by Clavien's classification divided into four eras (each consecutive 50
      cases) were compared. RESULTS: Donor characteristics of the four eras were
      generally comparable. Operative outcomes improved progressively through the four
      eras. From era 1 to era 4, operation time decreased from 598 minutes (range, 378
      932 minutes) to 391 minutes (range, 304-635 minutes). Blood loss also decreased
      from 500 mL (200-1600 mL) of era 1 to 251 mL (range, 95-595 mL) of era 4. Overall
      complication rate was 20.5% (41 of 200). Complications rates from eras 1 to 4
      were 34%, 16%, 16%, and 16%, respectively. The most common complications were of
      grade I (24 of 41, 58.5%). A late donor death occurred in era 4 from the
      development of a duodenocaval fistula 10 weeks postoperation, giving a donor
      mortality of 0.5% (1 of 200). CONCLUSIONS: This study validated the estimated
      morbidity and mortality of donor right hepatectomy of 20% and 0.5%, respectively.
      The data provide reference for counseling potential donors and setting the
      standards of donor right hepatectomy in the current era.

PMID- 17197974
TI  - Evaluation of race and insurance status as predictors of undergoing laparoscopic
      appendectomy in children.
AB  - OBJECTIVE: The objective of this study was to determine the relationship of race
      and socioeconomic factors and the method used for appendectomies in children
      (open vs. laparoscopic). SUMMARY BACKGROUND DATA: Previous studies have shown
      racial and insurance-related differences associated with the management of
      appendicitis in adults. It is not known whether these differences are observed in
      children. METHODS: Children (<15 years) undergoing appendectomy from 1996 to 2002
      were identified in the Nationwide Inpatient Sample. Severity of appendicitis and
      underlying chronic illnesses were determined by ICD-9 codes. Hospital
      characteristics evaluated included teaching status and location, children's
      hospital status, and volume of appendectomies. Hierarchical unadjusted and risk
      adjusted logistic regression analyses were performed. RESULTS: Among 72,189
      children undergoing an appendectomy for appendicitis, 11,714 (16%) underwent a
      laparoscopic appendectomy. Multivariate analysis showed that whites were more
      likely to undergo a laparoscopic appendectomy than blacks (odds ratio, 1.14; 95%
      CI, 1.03-1.25, P = 0.01) but not other races. A significant interaction between
      payer source and children's hospital designation was observed, with the odds of
      children with private insurance undergoing laparoscopic appendectomy being
      significantly higher than those without private insurance at nonchildren's
      hospitals but not at children's hospitals. CONCLUSIONS: There are significant
      racial and insurance-related differences in use of laparoscopic appendectomy in
      children that are most evident at nonchildren's hospitals. These findings provide
      evidence that factors at hospitals dedicated to children may lead to better
      access to new technologies.

PMID- 17197975
TI  - Asymptomatic cholelithiasis in children with sickle cell disease: early or
      delayed cholecystectomy?
AB  - SUMMARY BACKGROUND DATA: Our study aimed to evaluate the role of elective
      laparoscopic cholecystectomy (LC) in children with sickle cell disease (SCD) and
      asymptomatic cholelithiasis and, furthermore, to determine whether the outcome is
      related to the operation timing. METHODS: The records of 30 children with SCD
      diagnosed with cholelithiasis from June 1995 to September 2005 were
      retraspectively reviewed. All 30 children were asymptomatic at the time of the
      first visit, and an elective LC was proposed to all of them. The operation was
      accepted in the period of study by 16 children and refused by 14. During medical
      observation, 10 of the 14 children who refused surgery were admitted for severe
      biliary colics. Acute cholecystitis was diagnosed by abdominal ultrasound in 3
      cases and in 1 case choledocholithiasis, ultrasonographically suspected, was
      confirmed by magnetic resonance cholangiopancreatography (MRCP) and treated
      during endoscopic retrograde cholangiopancreatography (ERCP). All children,
      emergency admitted, underwent LC after the onset of symptoms. The patients were
      divided up into 2 groups (A: asymptomatic; B: symptomatic) depending on clinical
      presentation and operation timing and the respective outcomes were compared.
      RESULTS: Elective LC in asymptomatic children (group A) is safe with no major
      complications reported. During medical observation in children who refused
      elective surgery (group B), 6 biliary colics, 3 acute cholecystitis, and 1
      choledocholithiasis were observed. Three sickle cell crises occurred in
      symptomatic children during biliary colics. The correlation between
      cholecystectomy performed in asymptomatic children (group A) and cholecystectomy
      performed in symptomatic children (group B) showed significant differences in the
      outcome. Morbidity rate and postoperative stay increased when children with SCD
      underwent emergency LC. CONCLUSIONS: Elective LC should be the gold standard in
      children with SCD and asymptomatic cholelithiasis to prevent the potential
      complications of biliary colics, acute cholecystitis, and choledocholithiasis,
      which lead to major risks, discomfort, and longer hospital stay.

PMID- 17197976
TI  - Successful iliac vein and inferior vena cava stenting ameliorates venous
      claudication and improves venous outflow, calf muscle pump function, and clinical
      status in post-thrombotic syndrome.
AB  - OBJECTIVES: Stent therapy has been proposed as an effective treatment of chronic
      iliofemoral (I-F) and inferior vena cava (IVC) thrombosis. The purpose of this
      study was to determine the effects of technically successful stenting in
      consecutive patients with advanced CVD (CEAP3-6 +/- venous claudication) for
      chronic obliteration of the I-F (+/-IVC) trunks, on the venous hemodynamics of
      the limb, the walking capacity, and the clinical status of CVD. These patients
      had previously failed to improve with conservative treatment entailing
      compression and/or wound care for at least 12 months. METHODS: The presence of
      venous claudication was assessed by > or =3 independent examiners. The CEAP
      clinical classification was used to determine the severity of CVD. Outflow
      obstruction [Outflow Fraction at 1- and 4-second (OF1 and OF4) in %], venous
      reflux [Venous Filling Index (VFI) in mL/100 mL/s], calf muscle pump function
      [Ejection Fraction (EF) in %] and hypertension [Residual Venous Fraction (RVF) in
      %], were examined before and after successful venous stenting in 16 patients (23
      limbs), 6 females, 10 males, median age 42 years; range, 31-77 yearas, left/right
      limbs 14/9, using strain gauge plethysmography; 7/16 of these had thrombosis
      extending to the IVC. Contralateral limbs to those stented without prior I-F +/-
      IVC thrombosis, nor infrainguinal clots on duplex, were used as control limbs (n
      = 9). Excluded were patients with stent occlusion or stenoses, peripheral
      arterial disease (ABI <1.0), symptomatic cardiac disease, unrelated causes of
      walking impairment, and malignancy. Preinterventional data (< or =30 days) were
      compared with those after endovascular therapy (8.4 months; interquartile range
      [IQR], 3-11.8 months). Nonparametric analysis was applied. RESULTS: Compared with
      the control group, limbs with I-F +/- IVC thrombosis before stenting had reduced
      venous outflow (OF4) and calf muscle pump function (EF), worse CEAP clinical
      class, and increased RVF (all, P < 0.05). At 8.4 months (IQR, 3-11.8 months)
      after successful I-F (+/-IVC) stenting, venous outflow (OF1, OF4) and calf muscle
      pump function (EF) had both improved (P < 0.001) and the RVF had decreased (P <
      0.001), at the expense of venous reflux, which had increased further (increase of
      median VFI by 24%; P = 0.002); the CEAP status had also improved (P < 0.05) from
      a median class C3 (range, C3-C6; IQR, C3-C5) [distribution, C6: 6; C4: 4; C3: 13]
      before intervention to C2 (range, C2-C6; IQR, C2-C4.5) [distribution, C6: 1; C5:
      5; C4: 4; C2: 13] after intervention. At this follow up (8.4 months median),
      venous outflow (OF1, OF4), calf muscle pump function (EF), and RVF of the stented
      limbs did not differ significantly from those of the control; significantly worse
      (P < 0.025) were the amount of venous reflux (VFI), and the CEAP clinical class,
      despite the improvement with stenting. Incapacitating venous claudication noted
      in 62.5% (10 of 16, 95% CI, 35.8%-89.1%) of patients (15 of 23 limbs; 65.2%, 95%
      CI, 44.2%-86.3%) before stenting was eliminated in all after stenting (P <
      0.001). CONCLUSIONS: Successful I-F (+/-IVC) stenting in limbs with venous
      outflow obstruction and complicated CVD (C3-C6) ameliorates venous claudication,
      normalizes outflow, and enhances calf muscle pump function, compounded by a
      significant clinical improvement of CVD. The significant increase in the amount
      of venous reflux of the stented limbs indicates that elastic or inelastic
      compression support of the successfully stented limbs would be pivotal in
      preventing disease progression.

PMID- 17197977
TI  - Incisional herniation induces decreased abdominal wall compliance via oblique
      muscle atrophy and fibrosis.
AB  - OBJECTIVE: The purpose of this study is to measure abdominal wall myopathic
      histologic and mechanical changes during incisional herniation and its effect on
      incisional hernia repairs. SUMMARY BACKGROUND DATA: Unloaded skeletal muscles
      undergo characteristic atrophic changes, including change in fiber type
      composition, decreased cross-sectional area, and pathologic fibrosis. We
      hypothesize that these atrophic changes decrease muscle elastic properties and
      may contribute to the high laparotomy wound failure rate observed following
      incisional hernia repair. METHODS: A rat model of chronic incisional hernia
      formation was used. Failing midline laparotomy incisions developed into
      incisional hernias. Controls were uninjured and sham laparotomy (healed) groups.
      Internal oblique muscles were harvested for fiber typing, measurement of cross
      sectional area, collagen deposition, and mechanical analysis. Mesh hernia repairs
      were performed on a second group of rats with chronic incisional hernias or acute
      anterior abdominal wall myofascial defects. RESULTS: The hernia group developed
      lateral abdominal wall shortening and oblique muscle atrophy. This was associated
      with a change in the distribution of oblique muscle fiber types, decreased cross
      sectional area, and pathologic fibrosis consistent with myopathic disuse atrophy.
      These muscles exhibited significant decreased extensibility and increased
      stiffness. The healed (sham) laparotomy group expressed an intermediate phenotype
      between the uninjured and hernia groups. Recurrent hernia formation was most
      frequent in the chronic hernia model, and hernia repairs mechanically disrupted
      at a lower force compared with nonherniated abdominal walls. CONCLUSIONS: The
      internal oblique muscles of the abdominal wall express a pattern of changes
      consistent with those seen in chronically unloaded skeletal muscles. The internal
      oblique muscles become fibrotic during herniation, reducing abdominal wall
      compliance and increasing the transfer of load forces to the midline wound at the
      time of hernia repair.

PMID- 17197978
TI  - Methodologic quality of cost-effectiveness analyses of surgical procedures.
AB  - OBJECTIVE: The purpose of this study was to evaluate the methodologic quality of
      economic analyses of surgical procedures and to compare quality across
      publications. SUMMARY BACKGROUND DATA: With healthcare resources limited and
      technologies rapidly advancing across specialties, including surgery, there is
      increasing demand for evidence of cost-effectiveness. METHODS: A MEDLINE search
      identified English-language articles published from 1995 to 2004 that included
      economic analyses of surgical procedures. Two of the authors reviewed 110 studies
      and scored each based on compliance with 10 methodologic criteria. Data analyses
      used Cohen's kappa statistic, regression models, Mann-Whitney U tests, and
      Kruskal-Wallis tests. RESULTS: The 110 articles appeared in 79 different
      journals, including 57 articles in 37 surgical journals. Most journals (75%) had
      only 1 article eligible for inclusion. The average number of criteria met was
      4.1, with 10 articles meeting all 10 methodologic standards. Compliance rates for
      the 5 methodologic criteria most frequently neglected ranged from 34% to 45% in
      nonsurgical journals and 9% to 14% in surgical journals (P < 0.001). CONCLUSIONS:
      While methodologic guidelines for cost-effectiveness analyses have appeared in
      the medical literature, studies of cost-effectiveness in surgery often do not
      meet these criteria. As healthcare policy seeks to incorporate information from
      economic evaluations, it is increasingly important that surgical journals adhere
      to accepted guidelines and perform quality assurance on these studies. This may
      be aided by wider promulgation of the methodologic criteria in surgical journals
      or at surgical meetings.

PMID- 17197980
TI  - Contrast-enhanced intraoperative ultrasonography: a valuable and not any more
      monocentric diagnostic technique performed in different ways.

PMID- 17197981
TI  - Is there an increased risk of the vas deferens occlusion after mesh inguinal
      hernioplasty and what can we do about it?

PMID- 17197982
TI  - Ductoscopic biopsy of papillary tumors in women with nipple discharge.

PMID- 17197983
TI  - Stapled hemorrhoidopexy versus Milligan-Morgan hemorrhoidectomy.

PMID- 17197984
TI  - Perioperative radiation for rectal cancer and sexual dysfunction after TME: cause
      and effect?

PMID- 17197985
TI  - Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-1,
      an international multicenter trial.

PMID- 17197986
TI  - Gut hormone profiles following bariatric surgery favor an anorectic state,
      facilitate weight loss, and improve metabolic parameters.

PMID- 17198005
TI  - Age-related changes in central and peripheral corneal thickness: determination of
      normal values with the Orbscan II topography system.
AB  - PURPOSE: The thickness of corneal tissue is an important parameter in refractive
      surgery, Goldmann applanation tonometry, and corneal diseases. The purpose of the
      study was to record system-specific normal values with the Orbscan II system and
      to investigate the influence of sex and age on central and peripheral corneal
      thickness to characterize more precisely the anatomy of the cornea. METHODS: The
      Orbscan II topography system is a computer-assisted slit-beam scanning technology
      that can map the anterior section of the eye. It was used to take 2 measurements
      at 10-minute intervals on 777 eyes of 390 normal white subjects ranging in age
      between 10 and 80 years. Two hundred forty-two participants were men and 148 were
      women. The central corneal thickness and the nasal, superior, inferior, and
      temporal peripheral corneal thickness at a distance of 3 mm from the center were
      analyzed. No correction factor was used. Using nonparametric test methods, we
      carried out a statistical analysis of the parameters of sex and age. RESULTS: The
      mean central corneal thickness of all 777 eyes was 595 +/- 41 microm. No sex
      specific central difference was identifiable (P = 0.33), there was no significant
      difference between the sides (P = 0.23), and no significant difference was found
      between the first and second measurement. The group of 10- to 39-year-olds had a
      mean central corneal thickness of 591 +/- 41 microm, whereas that of 40- to 80
      year-olds was 600 +/- 39 microm, which was a significant difference (P = 0.03).
      The mean peripheral corneal thickness was 689 +/- 46 microm nasally, 688 +/- 42
      microm superiorly, 667 +/- 40 microm inferiorly, and 655 +/- 42 microm
      temporally. Nasally and superiorly, we found a significant negative correlation
      with age (Spearman rank correlation, P = 0.02). CONCLUSIONS: The normal values
      presented here are a suitable reference basis for future studies in whites.
      Peripheral corneal thickness is asymmetric and seems to undergo age-related
      anatomic changes. This information should be considered when planning penetrating
      keratoplasty and refractive surgery.

PMID- 17198006
TI  - Ocular wavefront aberrations in patients after diffuse lamellar keratitis.
AB  - PURPOSE: To study ocular wavefront aberrations after laser in situ keratomileusis
      (LASIK) in patients who developed diffuse lamellar keratitis (DLK). METHODS: A
      case-control evaluation of 47 patients with DLK and 30 uneventful LASIK-operated
      controls. Measurements of visual acuities, cycloplegic refraction, eye's wave
      aberrations using a LADARWAVE aberrometer (up to eighth order), and corneal
      topography were obtained after LASIK treatment. All of the surgeries were
      performed using the Hansatome or the Moria microkeratome and the LadarVision
      excimer laser system. RESULTS: Mean follow-up interval from the day of the
      operative procedure to the examination day was 6.26 (DLK group; range, 2-13
      months) and 6.23 months (control group; range, 3-9 months). Mean preoperative
      spherical equivalent was -3.7 D in patients with DLK and -3.7 D in controls. High
      order aberration S7+7 (P = 0.015) was statistically different in the DLK group
      from that in controls. High-order aberrations S3+3 (P = 0.091) and S8+4 (chi =
      8.014, P = 0.046) showed a tendency to be different from controls. Loss of best
      corrected visual acuity was greater in patients with DLK. CONCLUSIONS: The
      occurrence of DLK after LASIK surgery may not significantly affect the visual
      outcome.

PMID- 17198007
TI  - Fungal colonization and infection in Boston keratoprosthesis.
AB  - PURPOSE: To determine the incidence of and risk factors for fungal keratitis and
      endophthalmitis in patients with a Boston keratoprosthesis (KPro) and to
      determine whether surveillance cultures were helpful in predicting fungal
      infection. METHODS: A retrospective chart review was performed of 182 patients
      (202 eyes) who received a type 1 (through cornea) or type 2 (through cornea and
      lid) KPro between March 1, 1990, and December 31, 2004, and who were followed for
      at least 1 month (range, 1 month to 13 years; mean, 2.84 years). There were 148
      eyes with type 1 and 54 eyes with type 2. Beginning in late 1999, many eyes were
      given a prophylactic topical regimen containing vancomycin, and many eyes with
      type 1 KPro were given therapeutic contact lenses. Cases of fungal keratitis or
      endophthalmitis were analyzed. To determine the fungal colonization rate, 70
      surveillance cultures of the ocular or lid surface around the KPro optic were
      obtained of 36 uninfected KPro eyes (35 patients) at random time-points over 1
      year (August 2002 to July 2003). RESULTS: There were 4 definite and 1 probable
      fungal infections in 6893 patient-months of follow-up, or 0.009 fungal infections
      per patient-year. These included 3 cases of definite or probable Candida
      endophthalmitis (C. parapsilosis, C. glabrata, and C. albicans) and 2 cases of
      mold keratitis (Alternaria, Fusarium). The rate was higher in eyes receiving a
      vancomycin-containing topical prophylactic regimen than those with on a non
      vancomycin regimen (5 cases/2774 person-months vs. 0 cases/4119 person-months; P
      = 0.011). In eyes with type 1 KPro, the rate was higher with therapeutic contact
      lens wear than without (4/1682 vs. 0/3115 person-months; P = 0.015). Surveillance
      cultures did not predict fungal infection, and none of the 6 surveillance eyes
      colonized with fungi (all Candida) developed a fungal infection. The prevalence
      of fungal colonization in KPro eyes had not changed since our 1996 surveillance
      study (11% vs. 10%, P > 0.05). CONCLUSION: Fungal infections in KPro eyes have
      appeared since we introduced broad-spectrum antibiotic prophylaxis and
      therapeutic contact lenses 5 years ago, but the infection rate remains very low
      in our mostly New England-based patient population. Cleaning or replacing the
      contact lens on a regular basis and prescribing a short course of topical
      amphotericin at the first visible signs of fungal colonization may prevent these
      infections.

PMID- 17198008
TI  - Classifying the severity of corneal ulcers by using the "1, 2, 3" rule.
AB  - PURPOSE: To propose and define the "1, 2, 3" rule as a system of categorizing the
      severity of bacterial keratitis and to determine its value in predicting the
      likelihood of visual loss after healing of bacterial corneal infection. METHODS:
      Seventy patients were evaluated for infectious corneal ulcers by 2 cornea
      subspecialists (J.D.L., M.C.V.) at a tertiary facility between October 30, 2001,
      and November 1, 2004. Forty-one patients met the inclusion criteria. Visual
      acuities, ulcer characteristics, culture results, and treatment data were
      collected. RESULTS: The sensitivity of the "1, 2, 3" rule for detecting
      potentially sight-threatening (PST) ulcers that would result in 0.20 logMAR (2
      Snellen lines) or greater loss in best spectacle-corrected visual acuity (BSCVA)
      was 100%. The specificity of the "1, 2, 3" rule in correctly labeling an ulcer
      that did not cause vision loss as rarely sight threatening (RST) was 57.14%. The
      positive predictive value of the "1, 2, 3" rule was 28.57%. The negative
      predictive value of the "1, 2, 3" rule was 100%. CONCLUSIONS: Corneal ulcers
      classified as PST are at significantly higher risk for sustaining loss of BCSVA
      compared with RST corneal ulcers. The "1, 2, 3" rule is sensitive and specific
      enough to be clinically useful in predicting which ulcers are more likely to have
      vision loss and which ulcers are not.

PMID- 17198009
TI  - Role of amniotic membrane graft for ocular chemical and thermal injuries.
AB  - PURPOSE: To evaluate the results of amniotic membrane transplantation (AMT) for
      ocular surface reconstruction in chemical and thermal injuries. METHODS:
      Retrospective review of case records of patients who had undergone AMT for
      chemical injuries (January 1998 to May 2001). RESULTS: Seventy two eyes of 69
      patients were studied of which 24 were acute cases (median-2 days, range, 1-20
      days) and 48 were chronic cases (median-12.4 months, range, 1.02-95.8 months).
      Mean age was 22.4 years (SD +/- 13.34 years) and average follow up duration was
      7.8 months (SD +/- 7.1). Main clinical findings were symblephara (52.8%), corneal
      vascularization (51.3%), conjunctivalization (45.8%), Limbal ischemia (45.8%),
      Limbal stem cell deficiency (55.5%) and epithelial defect (48.6%). 18 cases were
      due to acid injuries (5 acute, 13 chronic), 52 were due to alkali (18 acute and
      34 chronic) and 2 cases were due to thermal burns (1 each acute and chronic).
      Overall success rate was 87.5% in acute cases and 72.9% in chronic cases.
      Indication-wise success rates were 94.3% for epithelial defect healing, 88.2% for
      symptomatic relief, 59.7% for ocular surface reconstruction, and 55% for
      improving limbal stem cell function. Success was not achieved in any outcome
      measure in 1/24 (4.2%) in acute group and 6/48 (12.5%) in chronic group.
      CONCLUSION: AMT helps in ocular surface reconstruction, promotes rapid epithelial
      healing and partially restores limbal stem cell function. It can be considered as
      an effective modality for the ocular surface restoration in chemical and thermal
      injuries in selected cases. Success rates in acute and chronic cases are
      comparable.

PMID- 17198010
TI  - Amniotic membrane transplantation in severe bacterial keratitis.
AB  - PURPOSE: To determine whether a combination of early amniotic membrane
      transplantation (AMT) and early topical corticosteroid treatment could be a safe
      adjuvant therapy during antibacterial treatment in severe bacterial keratitis
      (BK) for relieving pain, avoiding iatrogenic epithelial toxicity, and allowing
      earlier use of topical steroids. METHODS: In a prospective noncomparative case
      series, 12 patients with severe microscopically-proven BK were treated with
      immediate maximal topical antibiotics followed by AMT at 48 hours (single-layer
      epithelial side-down or multilayer epithelial side-up), plus topical steroid
      treatment at 72 hours. Pain relief (NRS-11 numeric rating pain scale) and the
      corneal epithelium healing were measured. RESULTS: The follow-up rate was 7.5
      person-months, with AMT performed once in 2 patients and twice in 10 patients
      with BK caused by Pseudomonas aeruginosa (5), Klebsiella pneumoniae (1),
      Moraxella cattharalis (1), Staphylococcus aureus (1), Staphylococcus epidermidis
      (2), or Streptococcus pneumoniae (1). A significant decrease in the pain score
      was noted from the admission day (median, 8; range, 7-10) to shortly after AMT
      (at day 3: median, 2; range, 1-3). Epithelial healing was achieved between 8 and
      45 days (mean, 25.5 +/- 9.7 days). Neither perforation nor neovascularization was
      observed. CONCLUSIONS: Early AMT combined with topical corticosteroid in severe
      BK provides immediate pain relief and allows epithelial healing.

PMID- 17198011
TI  - Relationship between travoprost and central corneal thickness in ocular
      hypertension and open-angle glaucoma.
AB  - PURPOSE: To evaluate whether treatment with travoprost, an F2a prostaglandin
      analog, affects central corneal thickness (CCT) and whether intraocular pressure
      (IOP) response to the medication is related to baseline CCT. METHODS: This was a
      prospective, interventional, nonrandomized, nonconsecutive, clinical trial. In
      this multicenter study, 379 total patients, 220 with newly or previously
      diagnosed open-angle glaucoma (OAG), 141 with ocular hypertension (OHT), and 18
      unspecified, were recruited from 15 Canadian sites. IOP and CCT assessments were
      performed at baseline and 6 weeks after treatment with travoprost. Patients on
      IOP-lowering therapy at the time of enrollment were washed out for 4 weeks before
      baseline examinations. IOP was measured with Goldmann tonometers and CCT with
      Accutome IV pachymeters. Statistical analysis was performed with S-PLUS software.
      RESULTS: Posttherapy mean IOP decreased by 6.31 mm Hg or 24.4% (P < 0.001), and
      regression analysis indicated relatively greater IOP reduction in patients with
      higher pretherapy IOP (slope = 0.64; 95% CI, 0.54-0.76). Mean CCT decreased by
      6.9 microm (P < 0.001). IOP reduction was not related to CCT reduction (slope =
      0.253; 95% CI, -0.232 to 0.739; P = 0.305). Percent IOP decrease was not related
      to baseline CCT (slope = -0.02; 95% CI, -0.06 to 00.02; P = 0.33) in the total
      study sample. When OHT and OAG groups were considered separately, the OAG
      patients had less percent IOP decrease with thicker baseline CCT (slope = -0.067;
      95% CI, -0.13 to -0.004; P = 0.037). CONCLUSIONS: Treatment with travoprost
      decreased IOP significantly and was associated with CCT thinning, which had
      little or no effect on actual IOP decrease. In the OAG group, IOP decrease was
      found to be statistically smaller in patients with thicker corneas.

PMID- 17198012
TI  - Evaluation and treatment of children with ocular rosacea.
AB  - PURPOSE: To describe the clinical presentation and treatment of ocular rosacea in
      children, an often unrecognized entity. METHODS: Retrospective chart review of 20
      patients (age, 22 months to 17 years) who presented during childhood with corneal
      pathology, lid margin disease, and skin changes consistent with ocular rosacea.
      All patients were evaluated by the Cornea/External Disease Division of a tertiary
      care facility, Bascom Palmer Eye Institute, Miami, FL, between 1990 and 2003.
      RESULTS: Sixty percent of patients improved after treatment with systemic
      erythromycin or doxycycline and topical low-dose steroid preparations. Ten
      percent of patients experienced no change in symptoms with treatment, and 30% of
      patients had incomplete follow-up to determine success of treatment. The patients
      maintained remission for up to 4 years after a slow taper of systemic treatment.
      The mean length of follow-up was 19.6 months (range, 0-9 years). CONCLUSIONS:
      Early recognition and treatment of ocular rosacea in children may improve patient
      outcome by limiting progression of corneal pathology, including scarring and
      vascularization.

PMID- 17198013
TI  - In vivo confocal microscopic evaluation of langerhans cell density and
      distribution in the corneal epithelium of healthy volunteers and contact lens
      wearers.
AB  - PURPOSE: To examine and compare the density and distribution of Langerhans cells
      (LCs) in the corneal epithelium of healthy volunteers and contact lens wearers.
      METHODS: A total of 225 eyes of 130 healthy volunteers (age, 17-81 years) without
      history of ocular inflammation, trauma, or surgery and 98 eyes of 55 contact lens
      wearers (age, 13-76 years) were examined in vivo with the combination of the
      Heidelberg Retina Tomograph II and in-house-invented Rostock Cornea Module.
      RESULTS: In healthy volunteers, in vivo confocal microscopy revealed LCs in 31%
      of all volunteers, with 37 of these 43 volunteers presenting LCs both in the
      center and the periphery of the cornea with densities of 34 +/- 3 and 98 +/- 8
      cells/mm, respectively. In the group of contact lens wearers, 55% of all corneas
      presented with LCs, and 11 of these 33 corneas revealed LCs at central and
      peripheral locations. Although LC densities were markedly higher in both the
      central (78 +/- 25 cells/mm) and the peripheral cornea (210 +/- 24 cells/mm) of
      contact lens wearers, the gradient of LC density from peripheral to central
      cornea was found almost identical in both groups. In the central cornea, LC
      density decreased with duration of contact lens wear. LCs were located at the
      depth of 35 to 60 microm (ie, the level of lower intermediate cells, basal cells,
      and subepithelial nervous plexus). LCs presented as either large cells bearing
      long processes or smaller cells lacking cell dendrites, most supposedly
      indicating mature and immature phenotype, respectively. CONCLUSIONS: In vivo
      confocal microscopy enables evaluation of LC density and distribution in corneal
      epithelium. LCs were found present both in the center and the periphery of the
      cornea without difference in distribution between healthy volunteers and contact
      lens wearers. However, contact lens wearers revealed almost twofold higher LC
      densities in both locations, implying chronic mechanical irritation of the cornea
      in response to the contact lens as foreign body. Taken together, analysis of LC
      using in vivo confocal microscopy provides helpful information for a better
      understanding of contact lens-disturbed ocular homeostasis.

PMID- 17198015
TI  - Deep Anterior Lamellar Keratoplasty (DALK): visual outcome and complications for
      a heterogeneous group of corneal pathologies.
AB  - PURPOSE: To review the visual outcome and complications of deep anterior lamellar
      keratoplasty (DALK), using Melles technique. METHODS: All patients undergoing
      DALK between December 1999 and March 2005 were routinely entered into a
      longitudinal study. DALK was attempted in 80 eyes of 68 consecutive patients.
      Descemet membrane perforation occurred in 11 eyes, of which 7 required conversion
      to penetrating keratoplasty. The visual and refractive outcome of these eyes is
      presented separately. The mean follow-up was 21.2 months. Best-corrected visual
      acuities (BCVAs), refraction, graft clarity, and complications were recorded at
      each visit and analyzed. RESULTS: The mean patient age was 34.2 years.
      Keratoconus was the main indication for surgery (58 eyes), followed by herpes
      simplex keratitis (6 eyes), corneal stromal dystrophy (5 eyes), stem cell failure
      with scarring (2 eyes), corneal dermoid (1 eye), and corneal opacity (1 eye). The
      mean central corneal thickness changed from 0.42 +/- 0.07 mm preoperatively to
      0.62 +/- 0.06 mm postoperatively. At latest follow-up, BCVA of 6/6 or better was
      present in 24.7%, 6/9 or better in 69.9%, and 6/12 or better in 84.9% of the
      eyes. The mean postoperative refractive cylinder was 3.31 +/- 2.59 D, and the
      mean spherical equivalent was -2.54 +/- 3.61 D; 52.2% of the eyes had a
      refractive cylinder less than +/-3 D and 49.3% of the eyes had a spherical
      equivalent less than +/-3 D. Rejection episodes occurred in 9.6% of the eyes but
      were successfully reversed in all eyes. Graft failure occurred in 1 eye with
      severe stem cell deficiency. CONCLUSION: This is the largest series of DALK cases
      using the Melles technique in a variety of corneal lesions. Our results confirm
      the usefulness and safety of this procedure in conditions with no endothelial
      involvement. Graft rejection remains a significant complication but is associated
      with good recovery because the endothelium is spared.

PMID- 17198014
TI  - Effect of proparacaine on central corneal thickness values: an evaluation using
      noncontact specular microscopy and pentacam.
AB  - PURPOSE: To study the effect of 1 drop of 0.5% proparacaine on central corneal
      thickness values monitored by nonspecular microscopy and Pentacam, a corneal
      topographer with rotating Scheimpflug camera. METHODS: Forty subjects were
      divided into 2 groups with 1 group measured with a noncontact specular microscope
      and the other group with Pentacam (Oculus, Inc., Wetzlar, Germany). One eye was
      randomly selected, and corneal thickness values were monitored every 30 seconds
      for 10 minutes. Baseline corneal thickness values were defined as the average of
      all measurements taken over 10 minutes. One drop of 0.5% proparacaine was
      instilled, and the corneal thickness values were monitored by the same instrument
      every 30 seconds for another 10 minutes after drug instillation. RESULTS: The 2
      groups shared similar age range, refractive error, and baseline corneal thickness
      values. The spontaneous variation of corneal thickness values was within 3 mum
      for 10 minutes before drug instillation. There was no obvious trend of corneal
      thickness value change after the instillation of local anesthetics. The variation
      of corneal thickness values against the baseline was within 5 mum. CONCLUSION:
      One drop of 0.5% proparacaine does not produce any significant change in central
      corneal thickness.

PMID- 17198016
TI  - Unique homologous siRNA blocks hypoxia-induced VEGF upregulation in human corneal
      cells and inhibits and regresses murine corneal neovascularization.
AB  - PURPOSE: To determine whether RNA interference (RNAi) could block hypoxia-induced
      upregulation of vascular endothelial growth factor (VEGF) in human corneal
      epithelial cells in vitro and inhibit and regress injury-induced murine corneal
      neovascularization in vivo. METHODS: siRNA selected on the basis of target
      sequence homology between mouse and human VEGF was placed into expression
      cassettes and transfected into human corneal epithelial cells. Hypoxia-induced
      VEGF synthesis was assayed. Also, the effect of a plasmid capable of directing
      the expression of an siRNA against VEGF when injected into mouse corneas 8 hours
      before alkali-mechanical trauma was studied. Leukocyte count, VEGF protein
      levels, and degree of neovascularization in corneas were compared with that of a
      control siRNA plasmid. Plasmids were injected 1 week after injury to assess the
      ability of RNAi to regress corneal neovascularization. RESULTS: Hypoxia-induced
      VEGF mRNA synthesis and protein secretion by human corneal epithelial cells was
      efficiently suppressed by an siRNA targeted against a sequence uniquely identical
      for the mouse and human VEGF genes. Intrastromal delivery of a plasmid expressing
      this siRNA before murine corneal injury suppressed corneal VEGF by 55.7% versus
      control (P = 0.014), leukocyte infiltration by 69.5% (P < 0.001), and
      neovascularization 1 week after injury by 72.3% (P = 0.001). At the regression
      time point, treated corneas had 72.8% less neovascularization (P < 0.001).
      CONCLUSIONS: RNAi significantly suppresses expression of VEGF induced by hypoxia
      in human corneal epithelial cells in vitro. In vivo, intrastromal delivery of a
      plasmid expressing siRNA against VEGF suppresses injury-induced VEGF expression,
      leukocyte infiltration, and angiogenesis and was able to regress corneal
      neovascularization.

PMID- 17198017
TI  - Carboxymethyl beta-glucan binds to corneal epithelial cells and increases cell
      adhesion to laminin and resistance to oxidative stress.
AB  - PURPOSE: Polysaccharides are frequently used as viscoelastic agents to improve
      pharmacokinetics of ophthalmic preparations. Recently, polysaccharides from yeast
      cell walls such as beta-glucans have emerged as bioactive molecules endowed with
      immunomodulatory and cytoprotective properties. In this study, we investigated
      the effects of carboxymethyl beta-glucan (CMG), a water-soluble derivative of
      yeast beta-glucan, on cultured rabbit corneal epithelial cells. METHODS: We
      developed a fluorescein-labeled CMG to visualize its binding to corneal cells by
      means of digital microscopy and image deconvolution. The effects of CMG on
      adhesion and survival of corneal epithelial cells exposed to noxious stimuli were
      also studied. RESULTS: CMG binds defined regions scattered throughout the body of
      corneal cells, suggesting binding specificity. Tridimensional reconstruction of
      fluorescence shows that binding is localized mainly at the plasma and nuclear
      membranes. Interestingly, CMG binding is highly represented at the level of focal
      adhesion of cells spreading onto laminin. Accordingly, CMG promotes adhesion of
      corneal epithelial cells to laminin without affecting their proliferation rate.
      CMG also protects cells from oxidative stress-dependent cell death, being
      ineffective in preventing ultraviolet B cytotoxicity. CONCLUSIONS: Data show that
      CMG dynamically binds to corneal epithelial cells, promoting cell adhesion and
      resistance to oxidative stress.

PMID- 17198018
TI  - Endothelial cell density in donor corneas: a comparison of automatic software
      programs with manual counting.
AB  - PURPOSE: Several automated systems have become available to determine endothelial
      cell density (ECD) of donor corneas. The purpose of this study was the comparison
      of 2 systems, the Endothelial Analysis System EAT V1.4 (Rhinetec, Duesseldorf,
      Germany) and the NAVIS Cell Count Version 3.4.1 (Nidek Technologies, Erlangen,
      Germany), against manual ECD counts. METHODS: During organ culture, the
      endothelium of 50 human corneas was photographed on both conventional film and
      digitally. Manual fixed-frame counting was performed on 2 photographs by 3
      experienced ophthalmologists. Three digital pictures of each cornea were analyzed
      semiautomatically on the Rhinetec EAT system V1.4. Images were imported and
      analyzed by the fully automatic mode of the NAVIS system V3.4.1 (which also
      offers a semiautomatic counting mode). In an additional experiment on 11 corneas,
      the NAVIS counts on the microscopy system previously used only for manual cell
      counts were directly compared with manual counts. RESULTS: Mean endothelial cell
      density obtained by manual counting of all observers was 2679 +/- 313 (SD)
      cells/mm. Values obtained by digital analysis with EAT were a mean of 1.3% higher
      (2713 +/- 286 cells/mm), which is not a significant difference. In contrast,
      analysis of the digital pictures with the fully automated NAVIS software mode
      showed a mean of 7.0% higher measurements (2867 +/- 111 cells/ mm), a significant
      difference (P = 0.0001). Altman-Bland analysis revealed that the fully automated
      NAVIS counts gave too low results for high ECDs and too high results for low
      ECDs. This result was confirmed by the direct comparison with manual counting.
      CONCLUSIONS: Fully automated analysis of ECD remains problematic. Validation of
      any computer-assisted system against manual counting is of importance.

PMID- 17198019
TI  - Comparison of topical dry eye medications for the treatment of
      keratoconjunctivitis sicca in a botulinum toxin B-induced mouse model.
AB  - PURPOSE: To compare the effects of topical dry eye medications including anti
      inflammatory agents and lubricant eyedrops for the treatment of
      keratoconjunctivitis sicca (KCS) in a botulinum toxin B (BTX-B)-induced mouse
      model. METHODS: CBA mice were randomized into 10 groups. The first 5 groups
      received a transconjunctival injection of saline into the lacrimal gland, and the
      remaining groups were injected with 0.05 mL of 20 mU BTX-B. Each group received
      treatment with 0.1% fluorometholone (FML), 0.05% cyclosporine A (CsA), a 50:50
      combination of FML and CsA, artificial tears, or saline 3 days after injections.
      Tear production, corneal staining, and blink rate were compared in each of the 10
      groups. RESULTS: Tear production in BTX-B-injected CsA-treated, FML-treated, and
      combined-treated groups started to return to baseline level within 2 weeks of
      treatment, whereas those treated with saline or artificial tears still exhibited
      reduction of lacrimation up to 4 weeks after injection. Topical FML significantly
      reversed the staining score within 1 week of treatment. The improvement of
      corneal staining in BTX-B-challenged combined-treated and CsA-treated groups
      occurred later within 2 weeks after treatment. No significant improvement in
      corneal staining was observed for the BTX-B-injected mice treated with artificial
      tears or saline. No significant changes were noted in blink frequency between the
      control and study groups undergoing the various dry eye therapies. CONCLUSION:
      The therapeutic effects of dry eye medications in a BTX-B-induced mouse model of
      KCS are similar to the human response.

PMID- 17198020
TI  - In vivo confocal microscopic findings of two siblings with Maroteaux-Lamy
      syndrome.
AB  - PURPOSE: To describe the clinical and in vivo confocal microscopic findings of
      the cornea in 2 male siblings with Maroteaux-Lamy syndrome. METHODS: Two male
      siblings 27 and 22 years of age who had been diagnosed with Maroteaux-Lamy
      syndrome underwent ophthalmologic assessment. In vivo confocal microscopy of
      their corneas was performed with Confoscan 3.0 (Vigonza, Italy). RESULTS: Slit
      lamp examination of the central and peripheral corneas of both siblings revealed
      mild haze and diffuse stromal opacities. The fundus examination of the older
      sibling was significant for left optic disc swelling and bilateral radial macular
      folds. In vivo confocal microscopy of the corneas of both cases revealed several
      microdeposits that were present extracellularly and within keratocytes in all
      stromal layers, ranging in size from 1.0 to 3.8 microm. Abnormal keratocytes
      containing hyporeflective vacuoles were present to a greater extent in the
      posterior and middle stromal layers compared with the anterior stroma. The
      endothelial cell layer, the subbasal nerve plexus, and the stromal nerves had
      normal morphologic features. CONCLUSIONS: In corneas of patients with Maroteaux
      Lamy syndrome, glycosaminoglycan deposition and abnormal keratocytes may be
      present in all stromal layers. The endothelial layer seems to be normal at the
      third decade of life in both subjects studied.

PMID- 17198021
TI  - Conjunctival provocation test for the diagnosis of ocular hypersensitivity to
      chlorobutanol.
AB  - PURPOSE: Conjunctival provocation test (CPT) is a useful tool for the
      determination of the reagent in patients with allergic conjunctivitis. Our aim is
      to present an unusual reaction of ocular hypersensitivity to chlorobutanol by
      using this technique. METHODS: This case describes a 56-year-old woman who
      presented intense ocular pruritus and conjunctival hyperemia with each
      instillation of Colircusi Fluotest (Alcon, El Masnou, Spain). Skin tests and CPTs
      were considered. RESULTS: Skin tests were all negative. CPTs were performed with
      commercially available ophthalmic products that were selected for their
      compositions. Chlorobutanol was presumed as the reagent through elimination.
      Positive CPT with purified chlorobutanol confirmed this hypothesis. CONCLUSION:
      CPT performed with commercially available products can be a useful, accessible,
      and inexpensive technique to orient the diagnosis of suspected ocular
      hypersensitivity to a pharmacologic component. To our knowledge, this is the
      first report of ocular hypersensitivity to chlorobutanol.

PMID- 17198022
TI  - In vivo confocal microscopy of polymorphic amyloid degeneration and posterior
      crocodile shagreen.
AB  - PURPOSE: To report the in vivo confocal microscopic findings of combined
      polymorphic amyloid degeneration and posterior crocodile shagreen and correlate
      these findings with clinical presentations and previous histopathologic analysis.
      METHODS: Case reports with confocal microscopic analysis and literature review.
      RESULTS: Three patients with bilateral corneal opacities presented to the Emory
      Eye Center Cornea Clinic for evaluation. The first patient, a 65-year-old woman,
      was noted to have bilateral, discrete, punctate, and filamentous refractile
      stromal opacifications that appeared to be concentrated in the deep stroma. The
      second patient, a 50-year-old man, had bilateral deep central stromal haze in a
      mosaic pattern with intervening cracklike clear zones. The third patient, an 80
      year-old woman, had bilateral deep stromal deposits similar to patient 1 in
      addition to bilateral deep central stromal haze in a mosaic pattern with
      intervening cracklike clear zones similar to patient 2. Confocal microscopy
      showed bright, enhancing punctate lesions in the deep stroma and anterior stroma,
      with unaffected areas between these regions in patients 1 and 3, and central
      acellular opacification of irregular intensity with intermittent linear clear
      zones within the normal posterior stromal bed in cases 2 and 3. The first patient
      was diagnosed with isolated polymorphic amyloid degeneration, the second patient
      was diagnosed with isolated posterior crocodile shagreen, and the third patient
      was diagnosed with combined polymorphic amyloid degeneration and posterior
      crocodile shagreen. CONCLUSION: These cases are, to our knowledge, the first to
      report confocal microscopic findings in isolated polymorphic amyloid degeneration
      and combined polymorphic amyloid degeneration with posterior crocodile shagreen.

PMID- 17198023
TI  - Recovery from macular phototoxicity after corneal triple procedure.
AB  - PURPOSE: Visual recovery from macular phototoxicity in 2 cases after prolonged
      exposure to operating microscope light from uncomplicated corneal triple
      procedure surgery. Recovery is discussed in the context of repair and
      regeneration. METHODS: Retrospective case reports. RESULTS: Immediately
      postoperatively, both patients reported positive scotomata and were found to have
      macular retinal pigment epithelial depigmentation. In 1 case, the fovea was
      involved. By 6 to 12 months, the scotomata had disappeared despite large areas of
      retinal pigment epithelial hyperpigmentation remaining. CONCLUSION: Recovery from
      macular phototoxicity occurs, although the mechanism remains unclear. Positive
      scotomata in these cases resolved over several months. The time scale of recovery
      was consistent with the time required for cellular replacement and possible
      differentiation from neural progenitor cells.

PMID- 17198024
TI  - Dendritic keratitis caused by an acyclovir-resistant herpes simplex virus with
      frameshift mutation.
AB  - PURPOSE: To report a case of acyclovir-resistant herpes simplex virus (HSV)
      keratitis after long-term, inconsistent use of topical acyclovir and
      fluorometholone. METHODS: A 70-year-old man with dendritic keratitis caused by an
      acyclovir-resistant HSV strain was examined. The 50% inhibitory concentration of
      different antiviral agents against the isolated virus and the DNA sequence of
      viral thymidine kinase were determined. RESULTS: The 50% inhibitory concentration
      of acyclovir and trifluorothymidine for the isolated HSV strain was 13.75 and
      0.28 microg/mL, respectively, indicating that the virus was resistant to
      acyclovir. DNA sequencing of the viral thymidine kinase revealed that this virus
      had a frameshift mutant with a G insertion in the 7Gs homopolymer. Topical
      trifluorothymidine was effective, and the epithelial lesion was completely
      resolved within 2 weeks. CONCLUSION: A typical form of dendritic keratitis was
      caused by an acyclovir-resistant HSV with frameshift mutation in a 7Gs
      homopolymer region.

PMID- 17198025
TI  - Perforated corneal ulcer with subsequent endophthalmitis in a patient with graft
      versus-host disease.
AB  - PURPOSE: To describe a case of a perforated corneal ulcer leading to a bacterial
      endophthalmitis in a patient with graft-versus-host disease (GVHD). METHODS:
      Clinical history and examination; slit-lamp photography; surgical intervention;
      laboratory evaluation including microbiology, polymerase chain reaction (PCR),
      flow cytometry, and cytopathology. RESULTS: A diagnostic and therapeutic pars
      plana vitrectomy was performed. The vitreous aspirate was evaluated with
      microbiology; PCR for herpes simplex, herpes zoster, and cytomegalovirus; flow
      cytometry; and cytopathology. The patient received intravitreal antibiotics and
      antifungal and antiviral medication. The vitreous culture grew Staphylococcus
      epidermidis. CONCLUSION: Patients with GVHD are at risk for corneal ulcers with
      subsequent perforation. Commensal ocular flora may seed the vitreous and cause an
      endophthalmitis. Patients with GVHD may develop a vitritis from many causes
      including viral, fungal, and bacterial etiologies or a relapse of their original
      disease. When patients with GVHD present with vitritis, consideration should be
      given to obtaining a large vitreous aspirate to establish the etiology.

PMID- 17198027
TI  - Unilateral congenital corneal keloid with anterior segment mesenchymal dysgenesis
      and subluxated lens: case report and review of literature.
AB  - PURPOSE: To report the unusual association of unilateral congenital corneal
      keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated
      lens. METHODS: A 20-year old man presented with a mass lesion involving the left
      cornea. The corneal lesion had been present since birth. On biomicroscopic
      examination, a well-defined vascularized, grayish-white mass occupying the whole
      of the left cornea was seen. The right eye showed multiple peripheral corneal
      opacities with iridocorneal adhesions, a poorly defined supranasal limbus, and a
      subluxated lens. Excision biopsy of the mass was done for histopathologic
      examination. RESULTS: Histopathologic examination of the excised corneal mass
      showed features consistent with that of a corneal keloid: thickened keratinized
      epithelium, absent Bowman membrane layer, and fibrovascular hyperplasia composed
      of hyalinized collagen fibers with irregular orientation of the collagen
      lamellae. During penetrating keratoplasty of the left eye, an anomalous iris
      pattern with poorly defined angle and a supranasal subluxated lens was also
      observed. Extraction of the subluxated lens was also done. The graft failed
      subsequent to a nonhealing persistent epithelial defect. CONCLUSION: Our case
      report highlights the rare association of a unilateral congenital corneal keloid
      with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens.

PMID- 17198026
TI  - Spectacle-induced ocular trauma: an unusual mechanism.
AB  - PURPOSE: To report an unusual, spectacle-related injury. METHODS: A 16-year-old
      boy wearing spectacles with polycarbonate lenses presented with an unusual,
      spectacle-related injury. Impact with the ball during a ball sport (cricket) led
      to extreme torsion of the frame with resultant direct blunt trauma to the right
      eye by the spectacle arm. On examination, the patient had a 10 x 10-mm area of
      conjunctivalized scleral dehiscence superiorly in Zones 2 and 3, with uveal
      prolapse. Superior retinal detachment was also noted. RESULTS: Patient underwent
      wound repair with a scleral patch graft with transscleral cryotherapy and sulfur
      hexafluoride injection. CONCLUSION: Although increased impact resistance of newer
      spectacle lens materials is assumed to reduce the incidence of ocular trauma,
      such unusual mechanisms may still lead to severe ocular trauma. We report this
      case to highlight an unusual mechanism of spectacle injury, hitherto unreported,
      and to show the continued need for use of eye protection while wearing
      spectacles.

PMID- 17198030
TI  - Shifting-bubble sign in big-bubble technique in deep anterior lamellar
      keratoplasty.

PMID- 17198028
TI  - Solitary myofibroma of the sclera.
AB  - PURPOSE: To report a novel case of solitary myofibroma involving the sclera.
      METHODS: Case report and review of the literature. RESULTS: A 19-year-old woman
      had an expanding and painful epibulbar mass clinically diagnosed as nodular
      scleritis that did not respond to anti-inflammatory therapy. A biopsy showed a
      proliferation of spindle-shaped cells that reacted strongly positively with
      immunoperoxidase stains for vimentin and smooth-muscle actin. The diagnosis of
      solitary myofibroma was made. Six months postoperatively, the patient was well,
      and the lesion had not recurred. CONCLUSIONS: Myofibroma should be considered in
      the differential diagnosis of an epibulbar mass, especially in the setting that
      would mimic nodular scleritis.

PMID- 17198032
TI  - Care of the patient with adult congenital heart disease.
AB  - The adult congenital heart disease (ACHD) patient population has numerous and
      distinctive needs and comprise a rapidly growing group within the modern day
      healthcare arena. Current treatment provisions along with recommendations for
      future specialized multidisciplinary ACHD teams are discussed. The exclusive
      needs of this patient population have forced professional groups to reconsider
      the availability and appropriateness of current healthcare delivery to this group
      of complex patients, whose survivability and life expectancy have continued to
      improve as a direct result of enhanced research, technology, medical, surgical,
      and nursing care. General care considerations including psychosocial issues and
      patient education are presented, and reveal the challenges and strengths of
      caring for this adult patient population within a pediatric facility. Congenital
      heart disease is a lifelong illness that requires a dedicated, consistent
      approach to healthcare delivery in order to guarantee quality care throughout the
      lifespan.

PMID- 17198033
TI  - Percutaneous interventions.
AB  - The catheterization laboratory is no longer limited to coronary arterial
      interventions. Physicians have been striving to make more interventions less
      invasive that now can include carotid, renal, and peripheral arterial stenting,
      as well as less invasive repair of atrial septal abnormalities. Even cardiac
      assist devices can be implanted percutaneously to bridge a critically ill patient
      to other modes of treatment. This article will give a brief overview of each
      intervention and identify important nursing care.

PMID- 17198034
TI  - Pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rare and debilitating disease
      characterized by abnormal proliferation and contraction of pulmonary vascular
      smooth muscle cells. The resulting increase in pressure and pulmonary vascular
      resistance results in progressive right heart failure, low cardiac output, and
      ultimately death if left untreated. PAH is defined by a persistent elevation in
      pulmonary artery pressure with normal left-sided pressures, differentiating it
      from left-sided heart disease. Symptoms progress from shortness of breath and
      decreasing exercise tolerance to right heart failure, with peripheral edema and
      marked functional limitation. Exercise-induced syncope, worsening symptoms at
      rest, and intractable right heart failure indicate critical disease. PAH may be
      idiopathic with no identifiable cause or associated with collagen vascular
      diseases, drugs, HIV, liver disease, and/or congenital heart disease. Familial or
      genetically mediated PAH accounts for a small percentage of cases. Advances in
      the understanding of pathobiological pathways that contribute to vascular
      proliferation and remodeling have resulted in new therapies that improve quality
      of life and survival. Emerging therapies focus on the nitric oxide, prostacyclin,
      and endothelin pathways. Nursing interventions are critical to ensure patients'
      success with these expensive and complex treatments and their optimal adjustment
      to living with PAH.

PMID- 17198036
TI  - Cardiovascular pharmacotherapy update for the intensive care unit.
AB  - Pharmacologic agents including vasodilators, inotropes, and vasopressors are
      frequently used in the critical care setting for management of the unstable
      cardiac patient. These medications are used to elicit varying effects on vascular
      resistance, myocardial contractility, and heart rate to help achieve desired
      hemodynamic and clinical endpoints. Therefore, it is important for the critical
      care nurse to have a practical understanding and working knowledge of
      cardiovascular pharmacotherapy in the intensive care unit setting. This article
      reviews the pharmacology and clinical utility of commonly used intravenous
      "vasoactive" medications encountered in the intensive care unit. We also
      highlight innovations in pharmacotherapy for this patient population, and provide
      practical considerations for the most appropriate and safe use of these
      medications.

PMID- 17198037
TI  - Cardiac resynchronization therapy.
AB  - About 30% of patients with left ventricular systolic dysfunction also have
      ventricular conduction delays (prolonged QRS duration greater than 0.12 second)
      most frequently seen as left bundle branch block. This intraventricular
      conduction delay causes nonsynchronous ventricular activation between the right
      ventricle and the left ventricle (or dyssychrony), compromising cardiac function.
      Cardiac resynchronization therapy, or biventricular pacing, is a recent
      intervention for ventricular dyssychrony that incorporates 3 leads for pacing the
      right atrium and simultaneous pacing of the right ventricle and left ventricle.
      Left ventricular lead placement can be difficult to implant because of coronary
      venous anatomy and can require longer procedure time for the patient. Restoring
      ventricular synchrony has been shown to decrease septal wall dyskinesis, decrease
      mitral regurgitation, increase left ventricular filling time, decrease pulmonary
      capillary wedge pressure, and reverse ventricular modeling.

PMID- 17198038
TI  - To pump or not to pump?
AB  - Coronary artery bypass grafting is performed on the beating heart and thus
      requires the use of cardiopulmonary bypass. To avoid the complications associated
      with cardiopulmonary bypass, off-pump bypass (OPB) is viewed as a desirable
      alternative. Technological advancements have made OPB a viable option in an
      expanding population of patients. As a result, the number of OPB surgeries
      performed annually in the United States has increased. Critical care nurses are
      increasingly likely to provide care for patients after off-pump surgery. The
      differences between on-pump and OPB surgeries affect the postoperative nursing
      care requirements. While there are many common aspects of postoperative cardiac
      care for these 2 groups of surgical patients, there is a need to focus on the
      unique aspects of care for OPB patients. Despite promising short-term results in
      OPB patients, questions surrounding this procedure remain. Studies are under way
      to determine long-term graft patency.

PMID- 17198039
TI  - Cardiac cell therapy: a treatment option for cardiomyopathy.
AB  - Cardiomyopathy is a common clinical disorder affecting the heart muscle. This
      disease process frequently leads to congestive heart failure and will often
      progress to end-stage heart failure. Present standard of care treatment options
      for cardiomyopathy include medical management, lifestyle changes, and surgical
      procedures including left ventricular assist devices as a destiny therapy or
      bridging to heart transplantation. Even despite advances in drug therapy,
      mechanical assist devices, and organ transplantation, more than half of the
      persons with cardiomyopathy will die within 5 years of diagnosis. Small
      uncontrolled clinical trials have demonstrated cardiac stem cells as a treatment
      option for cardiomyopathy. The theory for the individual or combined mechanism of
      action for stem cells includes (1) transdifferentiation to blood vessels or
      myocardium, (2) fusion with the native dysfunctional myocytes to augment
      function, and (3) homing that may be a systemic or panacrine response for
      recruiting other cells, and growth factors to help improve oxygen delivery and
      myocardial function. The field of cardiac cell therapy is rapidly progressing to
      gather more data with intermediate-size, double-blinded trials that will
      demonstrate the safety and efficacy of cell therapy.

PMID- 17198040
TI  - Frequency and pattern of medical emergency team activation among medical
      cardiology patient care units.
AB  - Medical emergency teams are developing across the United States. The organization
      and implementation for a rapid response team to failing medical-surgical patients
      has been shown to reduce in-house cardiac arrest rates. Further investigation
      into the frequency and pattern for rapid response team calls has been shown to
      have a diurnal pattern and clustered around times associated with routine care
      activities. The medical emergency calls in the descriptive analysis reveal that
      calls to the medical cardiology units constitute--% of the total calls. The calls
      are found to be called with--frequency during the hours of 7 AM and 7 PM. The
      frequency of calls is shown to be clustered around the times of. The small
      descriptive analysis here suggests that further investigation in the patterns and
      monitoring of patient for early recognition to call for help is still needed.

PMID- 17198042
TI  - Mechanical ventilation: looking for new paradigms.

PMID- 17198043
TI  - Cardiopulmonary interactions in patients with heart failure.
AB  - PURPOSE OF REVIEW: The purpose of this review was to summarize recent findings
      concerning the consequences of cardiopulmonary interactions in acute cardiogenic
      pulmonary edema, weaning from mechanical ventilation and fluid-responsiveness
      assessment by respiratory variations of stroke volume. RECENT FINDINGS: The
      efficacy of continuous or bilevel positive airway pressure in patients with acute
      cardiogenic pulmonary edema was strongly suggested by two recent meta-analyses.
      There is growing evidence to suggest that weaning-induced cardiac dysfunction and
      acute cardiogenic pulmonary edema could explain a large amount of liberation
      failure from mechanical ventilation. Despite a potential role for
      echocardiography and plasma measurements of B-type natriuretic peptide in
      demonstrating a cardiac origin to weaning failure, the demonstration of a
      significant increase in pulmonary-artery occlusion pressure during the weaning
      trial remains the gold standard for this purpose. In patients with heart failure
      there is no evidence for revisiting the reliability of the respiratory variation
      of stroke-volume surrogates to predict fluid responsiveness. SUMMARY: For
      clinical practice, the knowledge of cardiopulmonary interactions is of paramount
      importance in understanding the crucial role of mechanical ventilation for
      treating patients with heart failure and, by contrast, the deleterious
      cardiovascular effects of weaning in patients with overt or hidden cardiac
      failure.

PMID- 17198044
TI  - Noninvasive ventilation in patients with hypoxemic acute respiratory failure.
AB  - PURPOSE OF REVIEW: To discuss the recent literature concerning the use of
      noninvasive ventilation for hypoxemic acute respiratory failure. RECENT FINDINGS:
      The benefits of noninvasive ventilation for patients with hypoxemic acute
      respiratory failure are unclear. In immunocompromised patients and following
      thoracic surgery, there is a strong rationale for using noninvasive ventilation
      to treat acute respiratory failure. Prophylactic continuous positive airway
      pressure after abdominal or thoracic surgery and prophylactic noninvasive
      ventilation in patients at risk of extubation failure have proved beneficial.
      Recent studies show that noninvasive ventilation has a favourable impact in
      immunocompetent patients with acute lung injury/acute respiratory distress
      syndrome, but caution is required. In hypoxemic acute respiratory failure after
      extubation, one study reported excess mortality in patients treated with
      noninvasive ventilation, possibly related to the delay for intubation. A major
      issue is avoiding undue noninvasive ventilation prolongation and staying alert
      for predictors of early noninvasive ventilation failure. Caution, close
      monitoring, and broad experience are required. SUMMARY: Hypoxemic acute
      respiratory failure may benefit from noninvasive ventilation or continuous
      positive airway pressure, but undue prolongation should be avoided. In
      postextubation respiratory failure there is no evidence for routine use of
      noninvasive ventilation.

PMID- 17198045
TI  - Mechanical ventilation: let us minimize sleep disturbances.
AB  - PURPOSE OF REVIEW: This review provides a background in mechanical ventilation
      and sleep. RECENT FINDINGS: Sleep pattern in mechanically ventilated patients
      differs largely from physiological sleep. The ventilatory mode and the
      ventilatory settings could have an influence on the sleep quality and quantity.
      Pressure support ventilation can increase the sleep fragmentation and decrease
      the sleep quantity, due to central apneas when compared with assist control
      ventilation. An excessive level of ventilatory assistance during sleep promotes
      central apneas and ineffective efforts. These two respiratory events can trigger
      arousals and awakenings, thus altering the sleep quality and quantity in
      mechanically ventilated patients. Ventilatory settings adjusted according to the
      patient's effort during pressure support allow reducing the number of ineffective
      efforts and improve sleep quality when compared with a clinical adjustment. A
      physiological approach to set the ventilator and the ventilatory mode may improve
      sleep quality and quantity. SUMMARY: Minimizing the sleep alterations in
      mechanically ventilated patients could be obtained by setting the ventilator in
      such a way to avoid hyperventilation during the sleep stage. The impact of sleep
      derangements in patient outcomes is, however, unknown.

PMID- 17198046
TI  - Inhalation therapy in invasive and noninvasive mechanical ventilation.
AB  - PURPOSE OF REVIEW: The aim of this article is to discuss the various factors that
      influence aerosol delivery in mechanically ventilated patients and clarify
      optimal techniques for aerosol administration in this patient population.
      Clinical use of various inhaled therapies in patients receiving invasive and
      noninvasive mechanical ventilation is also discussed. RECENT FINDINGS: With
      optimal techniques for using pressurized metered-dose inhalers and nebulizers in
      ventilator circuits, the efficiency of inhaled drug delivery in mechanically
      ventilated patients is comparable to that in ambulatory patients. Techniques for
      enhancing inhaled drug delivery during noninvasive positive pressure ventilation
      are also being investigated. SUMMARY: Pressurized metered-dose inhalers of
      bronchodilator and corticosteroid aerosols are more efficient and convenient to
      use than nebulizers for routine therapy in ventilated patients. Nebulizers are,
      however, more versatile and are employed to generate aerosols of bronchodilators,
      corticosteroids, antibiotics, prostaglandins, surfactant, and mucolytic agents.
      Factors influencing drug delivery during noninvasive positive pressure
      ventilation are not fully understood as yet, and further work is needed to
      enhance drug delivery in this setting. Improvements in drug formulations and the
      design and efficiency of aerosol generating devices have led to increasing
      application of inhaled therapies in mechanically ventilated patients.

PMID- 17198047
TI  - Modulating cofactors of acute lung injury 2005-2006: any closer to 'prime time'?
AB  - PURPOSE OF REVIEW: Considerable progress has recently been made in understanding
      the modulation of acute lung injury by cofactors that are not traditionally
      considered 'pulmonary' in nature. We will review findings regarding some of these
      extrapulmonary cofactors, focusing on those most readily manipulated in the
      current clinical setting. RECENT FINDINGS: Recent studies have demonstrated that
      limiting fluid administration in the setting of acute lung injury might improve
      surrogate outcomes; that hypercapnea and induced hypothermia might protect
      against or attenuate acute lung injury; that corticosteroids can improve
      mechanics but not mortality in acute respiratory distress syndrome; a potential
      role for concomitant administration of colloid and diuretic in acute lung injury;
      and the potential benefits of inhaled beta agonists in acute lung injury.
      SUMMARY: There are a number of simple, low-cost, and rapidly deployable
      approaches to reducing the severity of acute lung injury that are not directly
      pulmonary in origin. These interventions could be rapidly implemented in any
      intensive care unit, once evidence for their efficacy and safety is adequate.

PMID- 17198048
TI  - Management of ventilator-associated pneumonia caused by multiresistant bacteria.
AB  - PURPOSE OF REVIEW: The inappropriate choice of antibiotics (in nearly one third
      of episodes) is the most important risk factor for death. Traditionally, a narrow
      spectrum drug was used first, and the most potent drugs were reserved for
      subsequent use. RECENT FINDINGS: As multidrug resistance increases in the
      intensive care unit in patients treated for nosocomial pneumonia, costs,
      mortality, and morbidity are rising. Although methicillin-resistant
      Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii are
      frequently considered together, they have different virulence, risk factors and
      susceptibilities, requiring different antimicrobial choices. Assessment of
      clinical resolution should be differentiated in the presence of acute lung
      injury. In the absence of biochemical markers, oxygenation and core temperature
      should guide therapeutic decisions. SUMMARY: As ventilator-associated pneumonia
      increases, empiric therapy should be based on local pathogen etiology and
      antibiotic resistant patterns. A new approach to consider is to start with a high
      dose, broad-spectrum antibiotic and then tailor the individual therapy based on
      microbiological results and clinical resolution. With the use of broad-spectrum
      antibiotics available in empiric therapy tailored after reassessment of the
      patient, there is hope for reducing costs, length of stay and mortality whereas
      the emergence of resistance will be minimized.

PMID- 17198049
TI  - Mass casualty respiratory failure.
AB  - PURPOSE OF REVIEW: The severe acute respiratory syndrome epidemic of 2002-2003,
      recent natural catastrophes, burgeoning concerns regarding intentional
      catastrophes, and the looming threat of an influenza pandemic have focused
      attention on large-scale, survivable respiratory failure. In this article, we
      review appropriate medical equipment, treatment space, and strategies to augment
      health professional staff in response to a massive increase in need for sustained
      critical care. RECENT FINDINGS: There is insufficient modern healthcare
      experience with mass casualty respiratory failure to develop evidence-based
      preparedness efforts. For this reason, initial efforts to augment critical care
      capability in response to disasters have relied on extrapolation from the routine
      critical care knowledge base, military medicine, critical care transport, and
      expert opinion. We review recently published documents on augmenting supplies of
      positive pressure ventilation equipment, ongoing projects for increasing health
      professional staff, and infection control issues during epidemics. SUMMARY: Mass
      casualty respiratory failure remains a largely unstudied field, but we believe
      informed decisions about equipment stockpiling and use, the development of
      creative operational concepts to increase staffing, and the careful
      implementation of rational infection control practices can lay a foundation for
      an appropriate response until additional data become available.

PMID- 17198050
TI  - Insights in pediatric ventilation: timing of intubation, ventilatory strategies,
      and weaning.
AB  - PURPOSE OF REVIEW: Mechanical ventilation is a common intervention provided by
      pediatric intensivists. This fact notwithstanding, the management of mechanical
      ventilation in pediatrics is largely guided by a few pediatric trials along with
      careful interpretation and application of adult data. RECENT FINDINGS: A low
      tidal volume, pressure limited approach to mechanical ventilation as established
      by the Acute Respiratory Distress Syndrome Network investigators, has become the
      prevailing practice in pediatric intensive care. Studies by these investigators
      suggest that high positive end expiratory pressure and recruitment maneuvers are
      not uniformly beneficial. High frequency oscillatory ventilation continues to be
      evaluated in an attempt to provide 'open lung' ventilation. Airway pressure
      release ventilation is a newer mode of ventilation that may combine the 'open
      lung' approach with spontaneous breathing. Prone positioning was demonstrated in
      a recent pediatric trial to have no effect on outcome, while calfactant was found
      to potentially improve outcomes in pediatric acute respiratory distress syndrome.
      Ventilator weaning protocols may not be as useful in pediatrics as in adults.
      Systemic corticosteroids decrease the incidence of post extubation stridor and
      may reduce reintubation rates. SUMMARY: Mechanical ventilation with pressure
      limitation and low tidal volumes has become customary in pediatric intensive care
      units, and this lung protective approach will continue into the foreseeable
      future. Further investigation is warranted regarding use of high frequency
      oscillatory ventilation, airway pressure release ventilation, and surfactant to
      assist pediatric intensivists in application of these therapies.

PMID- 17198051
TI  - Lung mechanics at the bedside: make it simple.
AB  - PURPOSE OF REVIEW: The aim of this review is to describe ventilator-patient
      interaction, employing the equation of motion and the curves obtained by the
      ventilator. Practitioners confronted with mechanically ventilated patients every
      day in intensive care units should be able to sort out from all data available
      from modern ventilators those relevant for choosing a correct ventilatory
      strategy for each patient. RECENT FINDINGS: Early determination of patient
      ventilator asynchrony, air-leaks and variation in respiratory parameters is
      important during mechanical ventilation. A correct evaluation of data, for
      patient safety and tailored ventilatory strategy becomes mandatory when non
      invasive ventilation by helmet or mask is applied. SUMMARY: The equation of
      motion is described and dynamic and static respiratory mechanics are analysed to
      highlight all those data that can influence decision-making in setting mechanical
      or assisted ventilation in invasively and non-invasively ventilated patients.

PMID- 17198052
TI  - Hyperoxia in the intensive care unit: why more is not always better.
AB  - PURPOSE OF REVIEW: Hyperoxic inspired gas is essential for patients with hypoxic
      respiratory failure; it is also suspected, however, as a contributor to the
      pathogenesis of acute lung injury. Several recent studies in humans, animals, and
      cell culture have identified mechanisms by which hyperoxia may exert deleterious
      effects on critically ill patients. This review identifies relevant new findings
      regarding hyperoxic lung injury in the context of providing guidance for future
      clinical studies. RECENT FINDINGS: Recent studies have clarified the roles of
      both receptor-mediated and mitochondrial cell death pathways in experimental
      hyperoxic lung injury. Studies in animals demonstrate that hyperoxia interacts
      with mechanical stretch to augment ventilator-induced lung injury. Finally,
      studies in humans implicate hyperoxia in impairment of host defense responses to
      infections. SUMMARY: Although hyperoxia has not been conclusively identified as a
      clinically important cause of lung injury in humans, animal data strongly
      implicate it. Reports of interaction effects between hyperoxia and both
      mechanical ventilation and host defense suggest that clinical studies of
      hyperoxia must take these variables into account. Accumulating data about how
      hyperoxia initiates cell death provide guidance for development of both
      biomarkers to identify hyperoxia-induced injury and pharmacological interventions
      to limit hyperoxia's adverse effects.

PMID- 17198053
TI  - How important is the measurement of extravascular lung water?
AB  - PURPOSE OF REVIEW: Accurate quantification of extravascular lung water is an
      important issue in the management of patients with pulmonary edema. The single
      transpulmonary thermal indicator method has been available since the late 1990s.
      Its simplicity and easy application make it clinically attractive. RECENT
      FINDINGS: Several experimental studies have confirmed the accuracy of the single
      transpulmonary thermal indicator technique in comparisons with postmortem
      gravimetric method. Whereas changes in extravascular lung water of less than 100
      200% are undetectable by other clinically applicable methods of lung injury
      assessment (chest radiograph and oxygenation), the single transpulmonary
      indicator has proven highly sensitive to small (10-20%) increases and is
      therefore useful to detect incipient pulmonary edema. In patients with sepsis or
      acute respiratory distress syndrome, extravascular lung water measurement offers
      information unobtainable by other means. SUMMARY: Extravascular lung water can be
      considered a relevant parameter that contributes to rational management of fluid
      and vasoactive therapy of many critically ill patients and offers a fuller
      picture of their overall lung function.

PMID- 17198054
TI  - Modulation and treatment of patient-ventilator dyssynchrony.
AB  - PURPOSE OF REVIEW: The coupling between ventilator delivered inspiratory flow and
      patient's demands both in terms of timing and drive is a challenging task that
      has become largely feasible in recent years. This review addresses the new
      advances to modulate and treat patient-ventilator dyssynchrony. RECENT FINDINGS:
      Patient-ventilator dyssynchrony is a common phenomenon with conventional modes of
      mechanical ventilation which influence the duration of mechanical ventilation.
      Inspection of pressure, volume and flow waveforms represents a valuable tool for
      the physician to recognize and take the appropriate action to improve patient
      ventilator synchrony. New developments have been introduced aiming to improve
      patient ventilator synchrony by modulating the triggering function and the
      variables that control the flow delivery and the cycling off. SUMMARY: Patient
      ventilator dyssynchrony may affect patients' outcome. New modes of assisted
      mechanical ventilation have been introduced and represent a major step forward in
      modulating patient-ventilator dyssynchrony.

PMID- 17198055
TI  - Tracheostomy in the critically ill: indications, timing and techniques.
AB  - PURPOSE OF REVIEW: Tracheostomy is one of the most common procedures performed in
      the intensive care unit. Indications, risks, benefits, timing and technique of
      the procedure, however, remain controversial. The decision of when and how to
      perform a tracheostomy is often subjective, but must be individualized to the
      patient. The following review gives an update on recent literature related to
      tracheostomy in the critically ill. RECENT FINDINGS: Surprisingly, few data are
      available on the current practice of tracheostomy in the intensive care unit
      setting. Very few trials address this issue in a prospective, randomized fashion
      (randomized controlled trial). Most reports include small numbers representing a
      heterogeneous population, describing contrary results and precluding any definite
      conclusions. Evidence seems to suggest that early tracheostomy, however, might be
      preferable in selected patients. SUMMARY: Due to increased experience and
      advanced techniques, percutaneous tracheostomy has become a popular, relatively
      safe procedure in the intensive care unit. The question of appropriate timing,
      however, has not been definitely answered with a randomized controlled trial.
      Instead, a number of retrospective studies and a single prospective study have
      shed some light on this issue. Most reports favor the performance of tracheostomy
      within 10 days of respiratory failure.

PMID- 17198056
TI  - Bibliography. Current world literature. Respiratory system.

PMID- 17198057
TI  - Antibiotics and Clostridium difficile: cause and cure.

PMID- 17198058
TI  - Picture imperfect pancreas?

PMID- 17198059
TI  - Short bowel syndrome: current medical and surgical trends.
AB  - Short bowel syndrome is a chronic malabsorptive state usually resulting from
      extensive small bowel resections. A combination of diarrhea, nutrient
      malabsorption, dysmotility, and bowel dilatation may constitute the clinical
      symptomatology of this syndrome. The remaining bowel undergoes a process called
      adaptation, which may replace lost intestinal function. Chronic complications
      include nutrient, electrolyte, and vitamin deficiencies. Therapy depends largely
      on the administration of various factors stimulating intestinal adaptation of the
      remaining bowel. If the patient despite medical therapy fails to return to oral
      diet alone, then long-term parenteral nutrition is required. However, long-term
      parenteral nutrition may gradually induce cholestatic liver disease. Surgical
      methods may be required for treatment including intestinal transplantation, as a
      last resort for the treatment of end-stage intestinal failure. The goal of this
      review is to analyze the clinical spectrum and pathophysiologic aspects of the
      syndrome, the process of intestinal adaptation, and to outline the medical and
      surgical methods currently used to treat this complicated group of patients.

PMID- 17198060
TI  - Epidemiology of bloodstream infections in patients receiving long-term total
      parenteral nutrition.
AB  - GOALS: To describe the epidemiology and microbiologic characteristics of
      bloodstream infections (BSIs) in patients receiving long-term total parenteral
      nutrition (TPN). BACKGROUND: Home TPN therapy has been reported as a risk factor
      for BSI. However, little knowledge exists regarding the epidemiology of BSIs in
      this patient group. STUDY: A descriptive, observational epidemiologic study of
      patients receiving long-term TPN from January 1981 to July 2005 was performed.
      Variables analyzed include age, gender, time of follow-up, number of BSIs,
      microbiologic characteristics, underlying disease necessitating long-term TPN,
      catheter type, complications related to TPN, and clinical outcome. RESULTS: Forty
      seven patients receiving long-term TPN were evaluated. The most frequent
      indication for long-term TPN was ischemic bowel disease (25.5%). The mean
      duration of follow-up was 4.5 years. Thirty-eight patients (80.9%) developed 248
      BSIs while receiving TPN. More than 1 BSI episode occurred in 78.9% of these
      patients, and 23.8% of BSI episodes were polymicrobial. The most prevalent
      pathogen was coagulase negative staphylococci (33.5%). The most frequent
      complication among patients with BSI was central venous thrombosis (44.7%). Five
      patients were intravenous drug users. There were 11 deaths among the patients on
      long-term TPN, 4 of these were related to infection and 4 were related to
      intravenous drug use. CONCLUSIONS: The incidence of BSI is high, and a
      significant proportion of BSIs in long-term TPN patients are polymicrobial and
      due to multidrug-resistant bacteria and fungi. Careful management of the infusion
      line is required and interventions are needed to reduce the risk of catheter
      related infections in this population.

PMID- 17198061
TI  - A preliminary study of melatonin in irritable bowel syndrome.
AB  - BACKGROUND AND AIMS: Melatonin is involved in the regulation of gut motility and
      sensation. We aimed to determine if melatonin was effective in improving bowel
      symptoms, extracolonic symptoms, and quality of life (QOL) in irritable bowel
      syndrome (IBS) patients. METHODS: Eighteen patients (aged 18 to 65 y; 6 females)
      were randomly assigned to receive either melatonin 3 mg (n=9) or matching placebo
      (n=9) at bed time for 8 weeks. The overall IBS scores, extracolonic IBS scores,
      QOL scores were assessed at 2, 4, 6, and 8 weeks during treatment and at 16, 24,
      and 48 weeks during follow up. RESULTS: Compared with placebo, melatonin taken
      for 8 weeks significantly improved overall IBS score (45% vs. 16.66%, P<0.05).
      The posttreatment overall extracolonic IBS score was significantly lower (49.16%
      to 13.88%, P<0.05) when compared with placebo group. The overall improvement in
      QOL score was 43.63% in melatonin group and 14.64% in placebo group that is
      statistically significant. CONCLUSIONS: The result of this study showed that
      melatonin has some beneficial role in IBS. Further studies using large number of
      patients may provide a definite answer.

PMID- 17198062
TI  - 13C-methacetin breath test shortened: 2-point-measurements after 15 minutes
      reliably indicate the presence of liver cirrhosis.
AB  - BACKGROUND AND GOALS: The 13C-methacetin breath test (MBT) measures the activity
      of the cytochrome P450 dependent enzyme system and has been developed to assess
      the functional hepatic mass. We evaluated simple modifications of the 13C-MBT to
      further increase its practicability and therefore clinical acceptance. STUDY: One
      hundred and four patients with different chronic liver diseases (including 35
      patients with histologically proven cirrhosis) and 65 healthy controls underwent
      the 13C-MBT. Breath test results of 2-point measurements were compared with
      conventional breath test results (cumulative recovery after 30 min) and liver
      histology. RESULTS: The 2-point-measurement at 0 and 15 minutes (with a cut-off
      <14.6 per thousand delta over baseline) had 92.6% sensitivity and 94.1%
      specificity in identifying the presence of cirrhosis compared with liver
      histology. The 2-point-measurements at 5 and 10 minutes also provided good
      discrimination between cirrhotic and noncirrhotic patients. CONCLUSIONS: The 13C
      MBT using 2-point-measurement of breath samples at baseline and after 15 minutes
      reliably indicates decreased liver function in liver cirrhosis. This
      simplification of the 13C-MBT will increase practicability and cost efficiency,
      thus facilitating its clinical acceptability.

PMID- 17198063
TI  - Clinical aspects of rifampicin-associated pseudomembranous colitis.
AB  - Pseudomembranous colitis (PMC) is known to develop after antibiotic
      administration, but antituberculosis agents are rarely associated with this
      disorder. We report 6 cases of PMC after rifampicin administration; the clinical
      manifestations, laboratory findings, imaging findings, and clinical course are
      described. The median age of patients was 68 years (range, 54 to 82 y). All
      patients were diagnosed with active pulmonary tuberculosis by sputum smear and
      culture, and 2 suffered from type 2 diabetes mellitus. The average interval
      between initiation of antituberculosis therapy and the onset of diarrhea was 19.8
      days. The anatomic distribution of PMC included the rectum and sigmoid colon in 5
      cases and up to the hepatic flexure in 1 case. All patients were cured with
      medical treatment, which include discontinuation of rifampicin and oral
      metronidazole and vancomycin. PMC recurred in 1 patient after retreatment with
      rifampicin. Our findings suggest that patients who are treated with
      antituberculosis agents, who develop acute diarrhea during or after therapy,
      should be evaluated for PMC.

PMID- 17198064
TI  - Iron-deficiency anemia as presentation of pouchitis.
AB  - GOALS: This study sought to describe the percentage and cause of anemia in
      patients who underwent ileal pouch with anal anastomosis (IPAA) for ulcerative
      colitis (UC), and to compare the distribution of complications in patients with
      and without anemia, especially pouchitis, after IPAA. BACKGROUND: IPAA is the
      surgical procedure of choice for UC. Complications include pouchitis (40%),
      strictures (30%), small bowel obstruction (10%), pelvic sepsis (<5%), and urinary
      and sexual dysfunctions (<5%). Few studies have described the prevalence of
      anemia after IPAA, but no conclusive findings have been reported. STUDY: Patients
      who had undergone IPAA for UC were recruited from the UPR Inflammatory Bowel
      Disease Clinic and the Gastroenterology Research Unit. Demographic and medical
      data were obtained. Anemia was diagnosed using standard hematologic criteria.
      Serum iron, ferritin, transferrin, folate, vitamin B12, erythropoietin, total
      iron-binding capacity, reticulocyte count, peripheral smear, and bone marrow
      aspirate were evaluated in patients with anemia. Data analysis was performed with
      EPI Info version 6.4d. RESULTS: Iron-deficiency anemia was identified in 55.5%
      (10/18) of patients and pouchitis was found in 77% (14/18). All 10 patients with
      anemia had pouchitis, whereas only 4 of the 8 without anemia had pouchitis. In
      half of the anemic patients, pouchitis was asymptomatic. CONCLUSIONS: Iron
      deficiency anemia may be a clinical presenting sign of pouchitis. Hemoglobin
      levels may be considered as surveillance tools for pouchitis in patients with
      IPAA.

PMID- 17198065
TI  - Anal plugs for the management of fecal incontinence in children and adults: a
      randomized control trial.
AB  - GOALS: To evaluate the contribution of the anal plug to the management of fecal
      incontinence in children and adults. BACKGROUND: Effective management of fecal
      incontinence remains problematic. Previous studies of an anal plug have yielded
      conflicting results. STUDY: A randomized controlled trial was conducted. The
      intervention was the Conveen anal plug (Coloplast Limited) used for 12 months.
      Outcomes measures included: generic measures of child health [Functional Status
      II-R, Child Health Questionnaire (CHQ-PF50) and Dartmouth Primary Care
      Cooperative Information Project Charts]; generic measures of adult health for
      patients and carers (the SF-36, and Patient Generated and Carer Generated
      indices); condition-specific measures for adults and children; qualitative
      interviews, bowel charts, and diaries. The main outcome measure was a condition
      specific score on a 0 to 100 scale, where 0 was the most severe and 100 was the
      least severe incontinence. RESULTS: Thirty-one intervention and 17 control
      patients were recruited. Fecal incontinence was due to 1 of 3 reasons:
      congenital, acquired, and neurogenic. At baseline, patients managed their
      condition preemptively or protectively. Intervention patients used the plug as a
      complete management substitute or as an adjunct to existing management. The
      majority of intervention respondents retained the plug most of the time. There
      was greater improvement from baseline in mean condition-specific score in
      intervention group compared with control group but this difference was not
      statistically significant (t test P=0.053). Complete data analysis using analysis
      of covariance showed the mean difference between the treatment groups in
      condition-specific score of 9.9 (95% confidence interval-1.4, 21.1). Intention to
      treat analyses using imputation showed similar results. There was generally
      greater improvement in intervention groups subjects using other measures for
      children, adults, and carers. CONCLUSIONS: The anal plug is of benefit to the
      majority of patients. It does not suit all eligible patients with in situ plug
      retention being a problem for some.

PMID- 17198067
TI  - Multidetector row CT of superior mesenteric artery syndrome.
AB  - GOALS: The purpose of this case series is to illustrate the diagnostic criteria
      of superior mesenteric artery syndrome (SMAS) using 16-slice multidetector row
      computed tomography (MDCT) angiography with multiplanar and 3-dimensional
      reconstructions. BACKGROUND: SMAS is a rare condition causing functional
      obstruction of the third portion of the duodenum. When suspected, diagnostic
      imaging can be performed with upper gastrointestinal, arteriography, or CT.
      STUDY: Four patients with clinical symptoms and correlative CT evidence of SMAS
      are described. Axial, multiplanar, and 3-dimensional rendered MDCT images were
      retrospectively reviewed by 1 investigator, who measured the aortomesenteric
      angle and aortomesenteric distance on a sagittal maximum intensity projection
      rendering, and compared these values with normal ranges described in the
      literature. RESULTS: In each patient, MDCT demonstrated gastric and proximal
      duodenal dilatation with abrupt narrowing of the third portion of the duodenum
      between the aorta and SMA. Sagittal maximum intensity projection images reliably
      demonstrated the decreased aortomesenteric angle (mean in subjects 13.5 degrees,
      normal range 28 to 65 degrees) and distance (mean in subjects 4.4 mm, normal
      range 10 to 34 mm) in all 4 patients. CONCLUSIONS: As opposed to traditional
      imaging modalities like upper gastrointestinal and mesenteric arteriography,
      which depict either the bowel or vasculature respectively, CT enables direct
      visualization of obstructed bowel owing to duodenal compression by the SMA.
      Multiplanar MDCT with 3-dimensional rendering provides sagittal reconstructions
      that can be used to confirm the CT criteria of decreased aortomesenteric angle
      and distance in SMAS.

PMID- 17198066
TI  - Tolerability and patient acceptance of sodium phosphate tablets compared with 4-L
      PEG solution in colon cleansing: combined results of 2 identically designed,
      randomized, controlled, parallel group, multicenter phase 3 trials.
AB  - GOALS: Evaluate patient tolerance and acceptance of a sodium phosphate (NaP)
      tablet purgative compared with a 4-L polyethylene glycol (PEG) solution.
      BACKGROUND: Characteristics and side effects of bowel purgatives deter patients
      from undergoing screening colonoscopy. Published data demonstrated comparable
      bowel cleansing with NaP tablets and a 4-L PEG solution in 2 phase for 3 studies.
      This report presents data on patient tolerability and acceptance. STUDY: Two
      identically designed, randomized, investigator-blinded, and multicenter trials
      were performed. Tolerability and patient acceptance were based on purgative
      regimen compliance, incidence of gastrointestinal adverse events, and patient
      responses to questionnaires. RESULTS: Eight hundred forty-five patients were
      assessed (420 and 425 in the tablet and PEG solution groups, respectively).
      Patient compliance with the tablet regimen was greater: 94% of patients took all
      the tablets compared with 57% completing the PEG solution regimen (P<0.0001).
      Nausea, vomiting, and bloating occurred significantly less often in patients
      taking NaP tablets (P<0.0001). Among patients taking tablets, 88.4% rated them
      "easy" or "slightly difficult" to take, compared with 60.6% of patients taking
      the PEG solution. The preparation's taste was rated "barely tolerable" or "not
      tolerable" by 1% of patients treated with NaP tablets and 23.6% treated with PEG
      solution. Drinking the required volume of clear liquid for the tablet or PEG
      preparation was rated "easy" or "slightly difficult" by 92.2% and 66.9% of
      patients, respectively. Almost all (90.7%) patients taking the tablets indicated
      they would take the same preparation in the future, compared with 67.1% of
      patients taking the PEG solution (P<0.0001 for each comparison). CONCLUSIONS:
      Tolerability and patient acceptance of a NaP tablet purgative were superior to 4
      L PEG solution.

PMID- 17198068
TI  - Should antihepatitis B virus core positive or antihepatitis C virus core positive
      subjects be accepted as organ donors for liver transplantation?
AB  - Since the introduction of liver transplantation as a routine surgical procedure
      for the treatment of end-stage liver disease, there has been an increasing gap
      between the number of available grafts and the number of patients on the waiting
      list. This has led transplant centers to expand the donor pool by different
      means. One of them has been the introduction of living donor liver
      transplantation. Other strategies include using less than optimal allografts from
      deceased donors, the so-called marginal donors, which include the use of grafts
      from older subjects, livers with moderate amounts of steatosis, or from donors
      with markers of past or current infection with hepatitis viruses who have absent
      or minimal liver biochemical or histologic injury. In this review, we will focus
      on the current use of allografts from donors with antihepatitis B core antibody
      and/or antibodies against hepatitis C virus in cadaveric and living donor liver
      transplantation.

PMID- 17198069
TI  - Hepatitis C in HIV-positive patients--treatment and liver disease outcomes.
AB  - Many human immunodeficiency virus (HIV) infected persons are coinfected with
      hepatitis C virus (HCV) and with the use of highly active antiretroviral therapy,
      liver disease from HCV has become an important cause of morbidity and mortality.
      The current guidelines recommend that human immunodeficiency virus and HCV
      coinfected patients be evaluated and treated for HCV if there are no major
      contraindications to treatment. Coinfected patients treated with pegylated
      interferon-a and ribavirin have sustained virologic responses (SVRs) of 27% to
      40% which for a variety of reasons are lower than those reported in HCV mono
      infected patients. Understanding that most patients will not achieve SVRs,
      strategies to evaluate for the role of maintenance interferon in delaying
      complications of liver disease are being evaluated. In patients who have failed
      prior treatment, cannot tolerate treatment, or who have contraindications to HCV
      treatment, the use of highly active antiretroviral therapy with careful
      monitoring for hepatotoxicity and aggressive counseling on alcohol and substance
      abuse may slow down fibrosis progression. As the data on liver transplantation in
      coinfected patients accumulate, patients with end stage liver disease should be
      referred early for evaluation in a transplant center. As new drugs for HCV are
      being developed, it will be of utmost importance to include coinfected patients
      earlier in the process on new drug trials and therapeutic strategies.

PMID- 17198070
TI  - Accuracy of endoscopic ultrasonography and magnetic resonance
      cholangiopancreatography for the diagnosis of chronic pancreatitis: a prospective
      comparison study.
AB  - BACKGROUND: The diagnosis of chronic pancreatitis (CP) remains challenging.
      Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography
      (MRCP) have been proposed as highly accurate diagnostic modalities. Although
      endoscopic retrograde cholangiopancreatography (ERCP) has been previously used as
      a gold standard, it is associated with a small but significant risk. We aim to
      compare the accuracy of EUS and MRCP with the composite gold standard using ERCP,
      surgical pathology, and/or long-term clinical follow-up. METHODS: Ninety-nine
      patients with clinical signs and/or symptoms suggestive of CP were prospectively
      enrolled. The diagnosis of CP by MRCP was established when one or more of these
      features were present: main duct dilation without obstruction, dilated side
      branches, intraductal stones, ductal irregularity, reduced T1-signal intensity,
      parenchymal atrophy, and reduced secretory response to secretin administration.
      The diagnosis of CP by EUS was made when 4 or more of the established criteria
      were present. Accuracy of all criteria used ("EUS only," "MRCP only," "either EUS
      or MRCP," and "both EUS and MRCP") was compared with the composite gold standard.
      RESULTS: Forty patients were diagnosed with CP by the composite gold standard
      whereas the remaining 59 patients were controls. EUS only seemed more sensitive
      but equally specific compared with MRCP only to diagnose CP. The combination of
      EUS and MRCP had a sensitivity of 98% for either EUS or MRCP and a specificity of
      100% for both EUS and MRCP. CONCLUSIONS: EUS and MRCP are highly accurate
      modalities for the diagnosis of CP and are complementary when used together. If
      confirmed in larger series, the diagnosis of CP by both EUS and MRCP is highly
      predictive and ERCP is unlikely to add any useful information.

PMID- 17198071
TI  - Predictors of outcomes after biliary and pancreatic sphincterotomy for sphincter
      of oddi dysfunction.
AB  - BACKGROUND: There are few data on combined pancreatic and biliary sphincterotomy
      for sphincter of Oddi dysfunction (SOD), especially regarding clinical features
      that might predict outcomes. We sought to examine the relative importance of
      various clinical features and the presence or absence of objective biliary
      abnormalities in determining responses to endoscopic therapy. METHODS: A cohort
      of consecutive patients with suspected SOD was treated with biliary
      sphincterotomy, with additional pancreatic sphincterotomy at initial or
      subsequent endoscopic retrograde cholangiopancreatography if there was abnormal
      pancreatic manometry in conjunction with pain refractory to biliary
      sphincterotomy, continuous pain, or a history of amylase elevation. Repeat
      intervention was offered until response was achieved or complete ablation of all
      treated sphincters was achieved. Response was assessed by patients using a 5
      point Likert scale, and multivariate logistic regression analysis used to
      identify predictors of response. RESULTS: Of 121 patients, 112 (92%) were female,
      105 (87%) postcholecystectomy, and by modified Milwaukee biliary classification
      18 (15%) were type I, 53 (44%) type II, and 50 (41%) type III. All patients
      underwent biliary sphincterotomy and 49 (40%) pancreatic sphincterotomy. Good or
      excellent response at final follow-up was reported by 83 (69%) of 121 patients,
      including 37 (61%) of 61 patients requiring repeated intervention. Response was
      not significantly different between biliary types I, II, and III. Patient
      characteristics (with adjusted odds ratios) that were significant predictors of
      poor response were normal pancreatic manometry (4.6), delayed gastric emptying
      (6.0), daily opioid use (4.0), and age <40 (2.7). Abnormal liver function tests
      or dilated bile duct were not significant. CONCLUSIONS: For the treatment of SOD
      incorporating pancreatic and biliary sphincterotomy, patient characteristics and
      pancreatic sphincter manometry may be more important predictors of outcome than
      the traditional classification based on liver chemistries and bile duct dilation.

PMID- 17198072
TI  - Prospective randomized comparison of minilaparoscopy and percutaneous liver
      biopsy: diagnosis of cirrhosis and complications.
AB  - BACKGROUND AND AIMS: Liver cirrhosis represents an advanced stage of hepatic
      fibrosis characterized by distortion of organ architecture and formation of
      regenerative nodules. Retrospective series reported percutaneous liver biopsy to
      miss cirrhosis in about 30%. The aim of this study was to prospectively compare
      diagnostic sensitivity regarding the detection of cirrhosis and the complication
      rates of percutaneous versus minilaparoscopic liver biopsy in chronic liver
      disease. METHODS: Eight hundred fifty-seven patients were randomized to
      percutaneous (415) or to minilaparoscopic liver biopsy (442). Macroscopic liver
      evaluation was documented as normal, fibrosis, or cirrhosis. Liver specimens were
      assessed blindly according to the modified Ishak score. RESULTS: Demographic and
      clinical data of procedure groups were comparable. Histologic grading alone
      diagnosed cirrhosis in 22.3% (n=85) of liver specimens obtained by percutaneous
      route compared with 26.0% (n=98) obtained by minilaparoscopy (P=0.270). By
      combining macroscopy and histology, minilaparoscopic staging diagnosed a
      significantly higher rate of liver cirrhoses with 33.8% (n=127) compared with
      percutaneous route with 22.3% (n=85) (P=0.001). Analysis of minilaparoscopic data
      revealed that 33 of the 128 cirrhoses were diagnosed by inspection only,
      suggesting a 26% underestimation of cirrhosis by histology alone. Severe
      complications occurred in 1.0% (n=4) of percutaneous and in 0.2% (n=1) of
      minilaparoscopic procedures (P=0.025). CONCLUSIONS: Minilaparoscopic evaluation
      based upon the combined macroscopic and histologic assessment is more sensitive
      with regards to the detection of cirrhosis and has a comparable safety profile.

PMID- 17198073
TI  - Response to pegylated interferon alpha-2b and ribavirin in children with chronic
      hepatitis C.
AB  - GOALS: The purpose of this communication is to report our observations on the
      treatment of a diverse group of adolescent patients who were chronically infected
      with hepatitis C and received pegylated interferon and ribavirin. BACKGROUND: The
      currently accepted optimal therapy for adults with chronic hepatitis C is weekly
      injections of pegylated interferon and twice daily oral ribavirin. Information on
      interferon alone or in combination with ribavirin for chronic hepatitis C in
      children is limited. There is no published information on pegylated interferon
      and ribavirin in pediatric patients who previously failed interferon therapy.
      REPORT: Ten patients 11 to 18 years old received weekly pegylated interferon and
      twice daily ribavirin for hepatitis C. Treatment continued for 48 weeks, except
      for 1 patient with hepatitis C virus type 3a who was treated for 24 weeks and 1
      patient who did not complete the course of treatment. The period of observation
      continued from November 2002 to December 2004. Within this group were 3 pediatric
      patients who had previously failed interferon therapy for hepatitis C. RESULTS:
      All but 1 patient had a viral response (no detectable virus) at some time during
      or after the treatment. Three patients achieved sustained viral response (no
      detectable virus 6 mo after the therapy). One patient who previously failed
      interferon therapy was among the sustained responders. CONCLUSIONS: In response
      to treatment with pegylated interferon and ribavirin, children and adolescents
      with chronic hepatitis C achieve results similar to those seen in adults.
      Previous antiviral therapy does not preclude positive response to pegylated
      interferon and ribavirin.

PMID- 17198074
TI  - Markedly elevated serum CA 19-9 levels in association with a benign biliary
      stricture due to primary sclerosing cholangitis.
AB  - We report on the case of a 55-year-old man with long-standing ulcerative colitis
      who developed jaundice. This led to a diagnosis of primary sclerosing cholangitis
      being made, with a dominant stricture in the common bile duct. Serum CA 19-9 was
      initially markedly raised at 26,321 U/mL but fell promptly into the normal range
      after stenting of the stricture. Long-term follow up of this patient has failed
      to show evidence of cholangiocarcinoma. We conclude that serum CA 19-9 levels
      need to be assessed in the clinical context of biliary obstruction and should
      ideally be measured after relief of that obstruction, as it may be falsely
      elevated due to benign biliary strictures.

PMID- 17198075
TI  - Abnormal glucose tolerance and non-esterified fatty acids (NEFAs) as predictors
      of non-alcoholic steatohepatitis (NASH): which Ash that ignites the NASH.

PMID- 17198077
TI  - Fatal hyperphosphatemia.

PMID- 17198078
TI  - Intra-abdominal lymphadenopathy and acute hepatitis A in an adult patient: a
      anecdotal radiological finding.

PMID- 17198079
TI  - A clinical development paradigm for cancer vaccines and related biologics.
AB  - Therapeutic cancer vaccines are a heterogeneous group of complex biologics with
      distinctly different clinical characteristics than cytotoxic agents. The current
      clinical development paradigm used for oncology drug development is based on
      criteria developed for cytotoxic agents. More flexible and focused developmental
      guidelines are needed to address the unique characteristics of therapeutic cancer
      vaccines. Over the course of 1 year, the Cancer Vaccine Clinical Trial Working
      Group, representing academia and the pharmaceutical and biotechnology industries
      with participation from the US Food and Drug Administration, defined in a
      consensus process the cornerstones of a new clinical development paradigm for
      cancer vaccines and related biologics. Four major topics were addressed: (1) end
      points for clinical trials, (2) trial designs and statistical methods, (3)
      technical and developmental challenges, and (4) combination therapy. The proposed
      paradigm suggests therapeutic cancer vaccines to be investigated in 2 general
      types of clinical studies: proof-of-principle trials and efficacy trials. Proof
      of-principle trials, which introduce a novel cancer vaccine into humans, should
      include a minimum of 20 or more patients in a homogenous, well-defined population
      in an adjuvant setting or without rapidly progressive disease in a metastatic
      setting to allow vaccines adequate time to induce biologic activity and should
      incorporate immune and molecular markers. Objectives should include initiation of
      a safety database, determination of dose and schedule, and demonstration of
      biologic activity as proof-of-principle. Biologic activity is defined as any
      effect of the vaccine on the target disease or host immune system using biologic
      markers as study end points, for example, clinical, molecular, or immune
      response. Immune response is demonstrated if determined in 2 separate,
      established and reproducible assays at 2 consecutive follow-up time points after
      the baseline assessment. If proof-of-principle trials show such immune response,
      or other biologic or clinical activity, efficacy trials may be initiated. If none
      of these end points is met, the clinical development plan should be reevaluated
      to decide if further development is warranted. Efficacy trials formally establish
      clinical benefit either directly or through a surrogate and are encouraged to be
      randomized studies. This is in contrast to single-arm phase 2 trials used for
      cytotoxic agents, which often use tumor response rate as the primary end point
      and historical controls as a comparator. Efficacy trials may use prospectively
      planned adaptive designs to expand from randomized phase 2 into phase 3 studies
      if well-defined trigger-point criteria are met, but the cost of incorporating
      such design elements should be carefully evaluated. Efficacy trials can also be
      exploratory randomized phase 2 trials or conventional phase 3 trials. In
      addition, conventional clinical end points can be adjusted to account for
      biologic features of cancer vaccines. The concept of efficacy trials allows for
      an early assessment of vaccine efficacy based on credible prospective data. This
      2-phase developmental paradigm supports a more flexible, expeditious, and focused
      clinical developmental process with early and informed decision making. In
      addition, this report addresses clinical development challenges and issues for
      combination therapies.

PMID- 17198080
TI  - Eosinophilic granulocytes and damage-associated molecular pattern molecules
      (DAMPs): role in the inflammatory response within tumors.
AB  - The development of a tumor over many years typically leads to reciprocal
      alternations in the host and the tumor, enabling tumor growth paradoxically in
      the setting of substantial necrosis and inflammation. When evaluating a tumor, it
      is important to assess 3 elements: (1) the quantity and quality of tumor
      associated leukocytes, (2) their state of activation, and (3) tumor
      microenvironment. Peripheral blood eosinophilia and tumor-associated tissue
      eosinophilia are frequently associated with some tumor types and also found after
      immunotherapy with IL-2, IL-4, granulocyte-macrophage colony-stimulating factor,
      and antibody to CTLA-4. Within several tumor types including gastrointestinal
      tumors, tumor-associated tissue eosinophilia is associated with a significantly
      better prognosis. The converse is true in other tumor types such as
      differentiated oral squamous cell carcinoma. On the basis of the emergent data,
      tumor-associated eosinophils have at least 2 dominant nonoverlapping activities:
      (1) destructive effector functions potentially limiting tumor growth as well as
      causing recruitment and activation of other leukocytes, (2) immunoregulative and
      remodeling activities which suppress immune response and promote tumor
      proliferation. The mechanism by which eosinophils in particular are recruited
      into tumor tissue is largely unknown. Candidates for causing eosinophil
      chemotaxis into tumor tissue are the released damage-associated molecular pattern
      molecules (DAMPs) including the nuclear protein high mobility group box 1. High
      mobility group box 1 is released upon necrotic cell death and secreted by many
      cells, particularly during periods of nutrient, hypoxic, or oxidant stress. This
      overview on eosinophil biology in the context of cancer and necrosis, introduces
      intriguing and novel strategies targeting eosinophils to enable more effective
      biologic therapy for cancer patients.

PMID- 17198081
TI  - T cell homing to tumors detected by 3D-coordinated positron emission tomography
      and magnetic resonance imaging.
AB  - A general hindrance to progress in adoptive cellular therapy is the lack of
      detailed knowledge of the fate of transferred cells in the body of the recipient.
      In this study, we present a novel technique for tracking of 124I-labeled cells in
      situ, which combines the high spatial resolution of magnetic resonance imaging
      with the high sensitivity and spatial accuracy of positron emission tomography.
      We have used this technique, together with determination of tissue radioactivity,
      flow cytometry, and microscopy, to characterize and quantitate the specific
      accumulation of transferred CD8+ T cells in tumor tissue in a mouse model.
      Transgenic CD8+ T cells, specific for the ovalbumin peptide SIINFEKL, were
      adoptively transferred to recipients carrying a subcutaneous tumor of the
      ovalbumin-expressing malignant melanoma cell line B16-OVA. The number of SIINFEKL
      specific CD8+ cells in the tumor tissue was determined by flow cytometry each day
      for 8 consecutive days after adoptive transfer. From low levels 1 day after
      injection, their number gradually increased until day 5 when an average of
      3.3x10(6) SIINFEKL-specific cells per gram tumor tissue was found. By applying
      the combined positron emission tomography/magnetic resonance imaging technique we
      were able to determine the position of the transferred, 124I-labeled SIINFEKL
      specific T cells in 3 dimensions in recipient mice, and could demonstrate a
      highly significant accumulation of the 124I label in and around the subcutaneous
      B16-OVA tumors compared with normal tissue. Accumulation of 124I was
      significantly higher in B16-OVA than in B16 tumors not expressing the OVA
      antigen.

PMID- 17198082
TI  - Defining the ability of cyclophosphamide preconditioning to enhance the antigen
      specific CD8+ T-cell response to peptide vaccination: creation of a beneficial
      host microenvironment involving type I IFNs and myeloid cells.
AB  - Although cyclophosphamide (CTX) has been clearly shown to enhance active specific
      and adoptive immunotherapies, the mechanism(s) underlying these beneficial
      effects have not been clearly defined. To define the impact of CTX
      preconditioning on the antigen-specific CD8 T-cell response to peptide
      vaccination, we used an adoptive transfer model based on the OT-1 T-cell receptor
      transgenic mouse. CTX preconditioning dramatically enhanced the antigen-specific
      CD8 T-cell response to peptide vaccination. Specifically, CTX significantly
      enhanced the expansion and function of responding CD8 T cells as demonstrated by
      flow cytometry and cytokine production. In parallel experiments, we attempted to
      define the mechanism(s) underlying these beneficial effects of CTX therapy. CTX
      therapy increased the relative number and activation status of myeloid dendritic
      cells, and was associated with the induction of significant levels of the
      inflammatory cytokines interferon-alpha, monocyte chemoattractant protein-1, and
      IL-6. Adoptive transfer experiments into type I IFNR-/- and CR3-/- mice confirmed
      that the beneficial effects of CTX were at least partially dependent on type I
      interferons and myeloid cells. Adoptive transfer of up to 150x10(6) naive spleen
      cells at the time of antigen-specific CD8 T-cell transfer did not abrogate the
      effects of CTX therapy, suggesting that the creation of a niche in the immune
      system may not be required. CTX decreased the absolute, but not relative number
      of CD4+CD25+ Treg cells, consistent with the possibility that regulatory T cells
      may be targeted by CTX therapy. Of note, combination therapy with CTX and a
      synthetic TLR3 agonist further enhanced the antigen-specific CD8+ T-cell
      response. Taken together, our data suggest that CTX modulates specific components
      of the innate immune system resulting in a beneficial host microenvironment.
      Specific targeting of these components may enhance the effectiveness of CTX
      preconditioning for adoptive immunotherapy.

PMID- 17198083
TI  - Interaction of Pneumocystis carinii with dendritic cells and resulting host
      responses to P. carinii.
AB  - To assess the interaction of Pneumocystis carinii with dendritic cells (DCs), and
      the consequences of the response of the host immune system to P. carinii antigens
      when DC are pulsed with P. carinii, murine DC were pulsed with P. carinii, and
      the resultant P. carinii host responses assessed in vitro and in vivo. P. carinii
      interacted with murine bone marrow-derived DC in vitro in part via mannose
      receptors. DC pulsed with P. carinii did not demonstrate increased expression of
      the cell surface markers MHC II, CD40, CD54, CD80 (B7.1), and CD86 (B7.2). The
      release of interleukin (IL)-4 was increased, but there was no increase in the
      release of interleukin (IL)-12p40, IL-10, tumor necrosis factor-alpha, IL-6, and
      nitrite compared with naive DC. In vivo administration of DC pulsed with P.
      carinii induced a P. carinii-specific response, generating CD4+ cells that
      proliferated and released IL-4, but not interferon-gamma, in response to P.
      carinii-pulsed DC in vitro. In vivo administration of DC pulsed with P. carinii
      also induced P. carinii-specific immunoglobulin (Ig)G1, IgG2a, and IgG2b, but not
      IgG3, antibodies in serum, and lung lavage fluid. Finally, CD4+ depleted mice
      immunized with DC pulsed with P. carinii demonstrated suppression of lung growth
      of P. carinii after intratracheal challenge with P. carinii at 3 and 16 weeks
      after immunization. These observations provide insight into DC-P. carinii
      interactions, and support the concept that a vaccine that includes DC pulsed with
      P. carinii can mount a humoral and T helper 2-type cellular response to P.
      carinii sufficient to suppress the growth of P. carinii in the lung.

PMID- 17198084
TI  - Recombinant interleukin-2 significantly augments activity of rituximab in human
      tumor xenograft models of B-cell non-Hodgkin lymphoma.
AB  - Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select
      immune effector cell responses associated with antitumor activity, including
      antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20
      monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The
      ability of rIL-2 to augment rituximab-dependent tumor responses was investigated.
      The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor
      xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the
      CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus
      rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as
      evidenced by significant tumor regressions and increased time to tumor
      progression, compared with rIL-2 and rituximab single agents. In contrast,
      rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and
      showed an increased response when combined with rituximab. Using in vitro killing
      assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and
      lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus
      rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role
      for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC.
      Antiproliferative and apoptotic tumor responses, along with an influx of immune
      effector cells, were observed by immunohistochemistry. Collectively, the data
      suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in
      part, through activation and trafficking of monocytes and natural killer cells to
      tumors. These data support the mechanistic and therapeutic rationale for
      combination of rIL-2 with rituximab in NHL clinical trials and for single-agent
      rIL-2 in rituximab-resistant NHL patients.

PMID- 17198085
TI  - Polarized type-1 dendritic cells (DC1) producing high levels of IL-12 family
      members rescue patient TH1-type antimelanoma CD4+ T cell responses in vitro.
AB  - Deficiencies in TH1-type immunity in patients with cancer may facilitate tumor
      progression and limit the effectiveness of current immunotherapy approaches. We
      hypothesized that Type-1 polarized dendritic cells (DC1) might be able to
      recondition patient antitumor CD4+ T cell responses toward the TH1-type in vitro.
      Although DC1 have been previously demonstrated to prime TH1 responses from naive
      CD4+ T cells, their impact on antigen-experienced TH responses remains unknown.
      We confirmed our own earlier observations that patient CD4+ T cell reactivity
      against melanoma-associated antigens (MAA) was weaker and less Type-1-polarized
      than their corresponding antiviral responses. Stimulation of patient CD4 T cells
      with peptide-pulsed DC1 (producing multiple IL-12 family member cytokines,
      including IL-12p70, IL-23, and IL-27) promoted robust TH1-type, epitope-specific
      T cell responses. Addition of exogenous IL-12 family member cytokines alone, or
      in combination, to nonpolarized DC was insufficient to equate to the benefits
      associated with DC1-based stimulation; however, IL-27 and IL-12p70 blockade
      neutralized the ability of DC1 cells to enhance TH1-type antitumor immunity in
      vitro. Notably, DC1-based stimulation seemed capable of "revitalizing" defective
      TH1-type responses within the CD45RO+ subset of antigen-experienced CD4+ T cells
      in melanoma patients. In addition to promoting elevated levels of IFN-gamma from
      responder CD4+ T cells, DC1-based stimulation also led to increased levels of IL
      12Rbeta2 and t-bet expression by TH cells. These results suggest that preexisting
      CD4+ T cell immunity to cancer is not relegated to Type-1 insufficiency and may
      be corrected via the application of DC1-based vaccination protocols.

PMID- 17198086
TI  - A novel approach to generate host antitumor T cells: adoptive immunotherapy by T
      cells maturing in xenogeneic thymus.
AB  - Mouse or human T cells developing in xenogeneic porcine thymus are functional.
      With efficient peripheral repopulation of mouse T cells by grafting fetal pig
      thymus (FP THY), B6 nude mice were immunized with inactivated syngeneic melanoma,
      B16 cells. Splenocytes from B16-immunized FP THY-grafted B6 nude mice efficiently
      killed B16, but not EL4 target cells in cytotoxicity assays in vitro. Adoptive
      transfer of splenocytes from B16-immunizd FP THY-grafted B6 nude mice to B16
      bearing B6 mice significantly prolonged recipient survival and inhibited B16
      solid tumor growth when B16 cells were injected IV or SC, respectively, compared
      with the identical controls. Splenocytes from nonimmunized FP THY-grafted B6 nude
      mice failed to protect B6 mice from B16-induced mortality. The present data have
      demonstrated that mouse T cells maturing in xenogeneic thymus have the ability to
      kill syngeneic tumor cells. This study may offer a novel resource to produce host
      antitumor T cells for adoptive immunotherapy of tumor patients.

PMID- 17198087
TI  - Effects of pentoxifylline on differentiation, maturation, and function of human
      CD14+ monocyte-derived dendritic cells.
AB  - Pentoxifylline (PTX) is a nonspecific phosphodiesterase inhibitor which has
      potent immunoregulatory and antiinflammatory effects. Although its
      immunomodulation property has been recognized, it is not clear whether PTX could
      affect dendritic cells (DCs), the most efficient antigen-presenting cells. The
      purpose of this study was to determine whether PTX could suppress DC
      differentiation, maturation, and its associated functions. Immature DCs (iDCs)
      were generated from human peripheral blood mononuclear cell CD14+ monocytes
      cultured with granulocyte macrophage colony stimulating factor and interleukin-4
      for 5 days. PTX concentration-dependently suppressed the expression of iDC
      differentiation markers including CD54, CD80, CD86, and human leukocyte antigen
      DR. In addition, PTX also inhibited DC maturation marker CD83 expression after
      stimulating DCs with lipopolysaccharide. Furthermore, PTX inhibited the antigen
      uptake ability of DCs when tested by fluorescein isothiocyanate-dextran
      endocytosis assay. PTX significantly reduced the production of TNF-alpha and IFN
      gamma in mature DCs (mDCs). Consequently, PTX-treated mDCs showed a reduced
      activity of mDC-induced T-cell allostimulation and proliferation by mixed
      lymphocyte reaction (MLR) assay. Therefore, PTX significantly inhibits CD14+
      monocyte-derived DC differentiation, maturation, antigen-uptake ability of iDCs,
      and antigen-presentation ability of mDCs possibly due to the suppression of TNF
      alpha and IFN-gamma production. These results suggested that inhibitory effects
      of PTX on DCs may contribute its antiinflammatory and immunoregulatory functions.

PMID- 17198088
TI  - Contact-activated monocytes: efficient antigen presenting cells for the
      stimulation of antigen-specific T cells.
AB  - Mature dendritic cells (DCs) are potent antigen presenting cells (APCs) that have
      been used in vaccine studies and adoptive immunotherapy protocols. For many
      clinical studies DCs are derived from monocytes in the presence of cytokines,
      which are expensive and often unavailable for clinical use. Here we describe a
      cytokine independent method for the differentiation of monocytes into APCs for
      the reactivation of antigen-specific memory T cells from both healthy donors and
      cancer patients. Contact activation of monocytes resulted in secretion of
      proinflammatory cytokines, such as IL-8, and increased cell surface expression of
      costimulatory molecules. To determine if activated monocytes (actMo) like DC can
      reactivate antigen-specific CTL, they were transduced with adenoviral vectors
      encoding the subdominant Epstein Barr virus antigens, latent membrane proteins
      (LMP) 1 and 2, which are expressed in Epstein Barr virus-positive malignancies.
      Stimulation of peripheral blood mononuclear cells with LMP1- and LMP2-expressing
      actMo activated LMP1- and LMP2-specific T cells, which could be further expanded
      with LMP1 or LMP2 expressing lymphoblastoid cell lines. The use of actMo as APCs
      simplifies the production/manufacture of antigen-specific T cells for clinical
      trials.

PMID- 17198089
TI  - Impact of interferon-alpha in combined chemoradioimmunotherapy for pancreatic
      adenocarcinoma (CapRI): first data from the immunomonitoring.
AB  - Data from a phase II trial combining chemoradiotherapy with IFN-alpha (CapRI
      scheme) for adjuvant treatment of pancreatic carcinoma are very encouraging.
      Therefore, a phase III trial comparing chemotherapy with the chemoradiotherapy
      with IFN-alpha scheme has been initiated in August 2004. Translational research
      with a focus on immunomodulation is performed in parallel to the study. Blood and
      serum samples are taken at various time points. Patients in arm A
      (chemoradioimmunotherapy) receive a single low-dose-Interferon injection before
      therapy to investigate the direct effect of IFN-alpha. So far samples from 44
      patients have been investigated for surface molecule expression, cytokine levels,
      natural killer cell cytotoxicity, and antigen-specific Granzyme B release.
      Patients in arm A showed 1 day after IFN-alpha injection a significant increase
      in spontaneous cytotoxicity; this effect was fading after repeated injections.
      Furthermore, cells releasing Granzyme B after stimulation with CA 19.9 and MUC-1
      protein increased under therapy. Five days after the first IFN-alpha injection,
      IL-12 and TNF-alpha serum levels peak. We observed significant increases of
      monocytes, peripheral dendritic cells, CD40 cells, central and effector memory T
      cells, and CD8 cells, CD4 cells decreased during therapy. All these effects were
      only observed in arm A patients and none of them in arm B patients. In
      conclusion, in a translational research project accompanying a challenging
      multimodality treatment trial including IFN-alpha, we observed an immediate
      activation of antigen-presenting cells and natural killer cells followed later on
      by antigen-specific activation. It will be most interesting if the immunologic
      data will show a correlation with the clinical course of the patients.

PMID- 17198090
TI  - Preliminary analysis of patients with progressive renal cell carcinoma vaccinated
      with CA9-peptide-pulsed mature dendritic cells.
AB  - Carbonic anhydrase-IXG250/MN (CA9) is a renal cell carcinoma (RCC)-associated
      antigen ubiquitously expressed in the clear-cell subtype of RCC. Two CA9-derived
      peptides have been identified defining a cytotoxic T-lymphocyte epitope and human
      leukocyte antigen (HLA)-DR epitope, able to induce T-cell responses in vitro. A
      phase I clinical trial was performed with CA9-peptide-loaded dendritic cells
      (DCs) in patients with progressive, cytokine-refractory metastatic RCC to assess
      the safety, toxicity, and induction of CA9-specific immunity. Patients with
      objective progressive metastatic RCC received 5 vaccinations of mature DCs pulsed
      with the CA9-derived peptides and keyhole limpet hemocyanine (KLH). Peripheral
      blood was collected at regular intervals, delayed-type hypersensitivity (DTH) was
      tested at baseline and after the last vaccination, and skin biopsies of positive
      DTH sites were collected for immunomonitoring purposes. Patients were also
      monitored for clinical responses. No significant toxicity was observed. All
      patients developed humoral responses against KLH, and demonstrated DTH
      conversion. Evaluation of biopsy material suggested an increased influx of T
      helper cells. In none of the immunomonitoring assays was evidence for the
      induction of CA9-peptide-specific immunity observed. No clinical responses were
      observed. The vaccination of DCs pulsed with KLH and 2 CA9-derived peptides was
      well tolerated. The lack of induction of CA9-peptide-specific immune responses
      indicates that this particular vaccine regimen is poor in inducing CA9-peptide
      specific immune responses.

PMID- 17198091
TI  - Persistence of tumor infiltrating lymphocytes in adoptive immunotherapy
      correlates with telomere length.
AB  - Transfer of autologous tumor-specific tumor infiltrating lymphocytes (TILs) in
      adoptive immunotherapy can mediate the regression of tumor in patients with
      metastatic melanoma. In this procedure, TILs from resected tumors are expanded in
      vitro, then administered to patients and further stimulated to proliferate in
      vivo by the administration of high dose IL-2. After in vitro expansion, TILs are
      often dominated by a few specific clonotypes, and recently it was reported that
      the persistence in vivo of one or more of these clonotypes correlated with
      positive therapeutic response. We and others have previously shown that repeated
      in vitro stimulation and clonal expansion of normal human T lymphocytes results
      in progressive decrease in telomerase activity and shortening of telomeres,
      ultimately resulting in replicative senescence. In the studies reported here, we
      therefore compared telomerase activity and telomere length in persistent and
      nonpersistent TIL clonotypes before transfer in vivo, and found a correlation
      between telomere length and clonal persistence. We also observed that TILs
      proliferate extensively in vivo in the days after transfer, but fail to induce
      substantial telomerase activity, and undergo rapid decreases in telomere length
      within days after transfer. Thus, in vivo loss of telomeres by clonotypes that
      have the shortest telomeres at the time of administration may drive these clones
      to replicative senescence, whereas cells with longer telomeres are able to
      persist and mediate antitumor effects. These findings are relevant both to
      predicting effectiveness of adoptive immunotherapy and in deriving strategies for
      improving effectiveness by sustaining telomere length.

PMID- 17198092
TI  - Risk of bowel perforation in patients receiving interleukin-2 after therapy with
      anti-CTLA 4 monoclonal antibody.

PMID- 17198093
TI  - Effect of head position on postoperative chemosis after prone spinal surgery.
AB  - Conjunctival swelling is a common finding in patients positioned prone. The
      purpose of this study was to evaluate the effect of head position on
      postoperative chemosis after prone spinal surgery. On the basis of the head
      position, 108 patients scheduled for prone lumbar surgery were randomly allocated
      to 1 of 2 groups: head neutral group (n=54) versus head down (HD) group (n=54).
      Head position was defined as neutral when the imaginary line from the occipital
      protuberance to the top of C7 spine process is parallel to the operating table.
      HD position was maintained by adjusting the height of the prone headrest 5 cm
      lower than neutral position. Chemosis was evaluated after surgery. The severity
      of chemosis, which was graded as none, mild, moderate, and severe, showed
      statistically significant difference between the head neutral group [24 (44%), 25
      (46%), 3 (6%), 2 (4%), respectively] and HD group [10 (19%), 23 (43%), 17 (31%),
      4 (7%), respectively, P<0.01]. Positive fluid balance and duration of surgery
      were risk factors for the development of postoperative chemosis. This result
      suggested that neutral head position, smaller fluid administration, and shorter
      duration of surgery were useful in decreasing the development of postoperative
      chemosis after prone spinal surgery.

PMID- 17198094
TI  - A new qualitative interleukin-6 bedside test can predict pneumonia in patients
      with severe head injury--comparison to the standard Immulite test and a
      semiquantitative bedside test.
AB  - Severe head injury (SHI) leads to systemic immunosuppression, which is processed
      by central mechanisms and is associated with a high risk of pneumonia. The timely
      identification of an immunodepressed condition in SHI patients might help prevent
      infections by changing the intensive care strategy. The aim of this prospective
      study is to evaluate a new method for identifying immunodepression and predicting
      pneumonia. We correlated interleukin (IL)-6 levels determined by the standard
      test (Immulite) and performed by specialized laboratories with those obtained
      using the new bedside test (PicoScan) with the occurrence of pneumonia in
      patients with SHI. Thirty-two patients with isolated SHI were investigated.
      Analyses were performed on serum samples taken 2 to 24 hours after trauma.
      Pearson correlation coefficient was 0.924 (P<0.001) for IL-6 values determined by
      PicoScan versus Immulite and Spearman rho was 0.572 for visual interpretation
      versus Immulite (P=0.01). Immulite and PicoScan have a positive predictive value
      of 91% and 100%, respectively, and a negative predictive value of 76% and 86%.
      The present study investigated for the first time the determination of IL-6
      concentrations by PicoScan in patients. Our findings show a good correlation with
      the results of the standard Immulite test and suggest that the PicoScan may be
      used as a handy tool to predict pneumonia in SHI patients.

PMID- 17198095
TI  - The efficacy of 5-HT3 receptor antagonists for the prevention of postoperative
      nausea and vomiting after craniotomy: a meta-analysis.
AB  - The purpose of this meta-analysis was to assess the efficacy of prophylactic
      administration of 5-HT3 receptor antagonists for postoperative nausea and
      vomiting in neurosurgical patients at 24 and 48+ hours. After a systematic
      search, 7 published randomized placebo controlled trials involving 448 craniotomy
      patients (222 treatment, 226 control) were included in the meta-analysis. Study
      drugs included ondansetron, granisetron, and tropisetron. The cumulative
      incidence of emesis was significantly reduced in the treatment group at 24 hours
      [relative risk (RR)=0.50, 95% confidence interval (CI): 0.38-0.66] and 48+ hours
      (RR=0.52, 95% CI: 0.36-0.75). There were no differences between the treatment and
      control groups in the cumulative incidence of nausea at 24 hours (RR=0.76, 95%
      CI: 0.54-1.06) and 48+ hours (RR=0.81, 95% CI: 0.62-1.06). The cumulative
      incidence of both nausea and vomiting continued to increase after 24 hours in
      both groups. Despite the ability of 5-HT3 receptor antagonists to reduce emetic
      episodes, future investigations should seek to address the control of
      postoperative nausea and to reduce further postoperative emesis in this
      population.

PMID- 17198096
TI  - Activations of nPKCepsilon and ERK1/2 were involved in oxygen-glucose deprivation
      induced neuroprotection via NMDA receptors in hippocampal slices of mice.
AB  - Accumulated reports have suggested that activation of protein kinase C (PKC)
      isoforms may involve the activation of extracellular signal-regulated kinases
      (ERKs) in the neuronal response to ischemic/hypoxic stimuli. We have previously
      demonstrated that the membrane translocation of novel PKC (nPKC) epsilon
      increased in the early phase of cerebral ischemic/hypoxic preconditioning of
      mice. In this study, we used Western blot analysis and propidium iodide stain to
      determine whether the activations of nPKCepsilon and ERKs were involved in oxygen
      glucose deprivation (OGD)-induced neuroprotection via N-methyl-D-aspartate (NMDA)
      receptors. The hippocampal slices of mice were exposed to OGD for 10 (OGD10) or
      45 minutes (OGD45) to mimic mild (causing ischemic/hypoxic preconditioning) and
      severe (causing severe OGD) ischemia/hypoxia, respectively. We found that OGD10
      induced nPKCepslilon membrane translocation was mediated by NMDA receptors, and
      both OGD10 and NMDA (1 microM, 30 min) pretreatment could protect Cornu Ammonis
      region 1 neurons against the subsequent severe OGD45. In addition, nPKCepsilon
      translocation inhibitor, epsilonV1-2 (1 microM, 30 min), and ERKs upstream
      mitogen-activated protein/extracellular signal regulated kinase kinase inhibitor,
      PD-98059 (20 microM, 30 min), could significantly inhibit OGD10 and NMDA-induced
      neuroprotection. These results suggest that OGD10-induced neuroprotection against
      severe OGD45 in the Cornu Ammonis region 1 region of the hippocampal slices was
      mediated by the activations of NMDA receptors, nPKCepsilon, and the downstream
      ERKs.

PMID- 17198097
TI  - Giant intracranial aneurysms treated with deep hypothermia and circulatory
      arrest.
AB  - The use of deep hypothermic circulatory arrest (DHCA), using groin cannulation
      with the chest closed (CCDHCA), has improved the surgical treatment of large and
      giant cerebral aneurysms. Twelve consecutive ASA I-II patients (10 women and 2
      men), with a mean age of 35 years (range 14 to 55 y) underwent DHCA for clipping
      or trapping of their aneurysm (giant, n=10; large, n=2; 42% posterior
      circulation), under balanced general anesthesia. Intraoperative standard monitors
      were completed with jugular oxygen saturation, pulmonary artery, pulmonary artery
      occlusion, central venous pressures, electroencephalography, evoked potentials,
      and cerebral (subdural), and core temperature. At the start of circulatory
      arrest, brain temperature was 15.1+/-1.1 degrees C (range 13.5 to 17.5), and core
      temperature 14.1+/-1.1 degrees C (range 12.7 to 17.0). Mean circulatory arrest
      time was 26.5+/-13.9 minutes (range 9 to 54) and anesthesia lasted 14+/-1 hours.
      Only one patient underwent DHCA with standard sternotomy, because of aortic
      insufficiency. Follow-up (up to 70 mo) revealed no deaths and Glasgow Outcome
      Scale at 6 months revealed good recovery in 9, moderate disability in 1, and
      severe disability in 2 patients. Selected patients with large/giant intracranial
      aneurysms, deemed unapproachable by conventional surgical techniques, were
      successfully treated using CCDHCA. Mortality rate was 0% and neurologic
      complications occurred in 25% of the patients.

PMID- 17198098
TI  - Hemodynamic changes due to infiltration of the scalp with epinephrine-containing
      lidocaine solution: a hypotensive episode before craniotomy.
AB  - Epinephrine-containing lidocaine solution is commonly infiltrated on the scalp
      before craniotomy. But the hemodynamic changes caused by epinephrine-containing
      lidocaine solution have been less intensely studied. A prospective randomized
      double blind control study was designed to observe hemodynamic changes caused by
      epinephrine-containing lidocaine solution in neurosurgical operations under
      general anesthesia. One hundred twenty patients undergoing scheduled craniotomy
      were allocated randomly to 4 groups. All the patients received 1% lidocaine 16 mL
      with different dose (concentration) epinephrine: group 1 with 40 microg (2.5
      microg/mL); group 2 with 80 microg (5 microg/mL); group 3 with 160 microg (10
      microg/mL); and group 4 (control group) without epinephrine. mean arterial
      pressure (MAP) and heart rate were recorded at 30-second interval in 5 minutes
      after the beginning of local infiltration. In group 1, group 2, and group 3, the
      lowest MAP and the highest MAP during this period also were recorded. Bleeding
      was assessed after raising the craniotomy flap. Compared with the baseline,
      significant hemodynamic changes, particularly decrease in MAP with increase in
      heart rate at 1.5 minutes after the beginning of local infiltration, were
      observed in group 1, group 2, and group 3 (P<0.001), but not in group 4. The
      highest MAP increased significantly compared with the baseline in group 3
      (P<0.05), but not in group 1 or group 2. Epinephrine-containing lidocaine
      solution reduced bleeding significantly (P<0.01). Infiltration with epinephrine
      containing lidocaine solution elicits temporary but significant hemodynamic
      changes including hypotension before craniotomy. Commonly clinically used
      concentrations of epinephrine (2.5 to 10 microg/mL) can reduce the bleeding on
      the scalp.

PMID- 17198099
TI  - Dexmedetomidine sedation during awake craniotomy for seizure resection: effects
      on electrocorticography.
AB  - Patients with refractory seizures may undergo awake craniotomy and cortical
      resection of the seizure area, using intraoperative functional mapping and
      electrocorticography (ECoG). We used dexmedetomidine in 6 patients, transitioning
      successively from the asleep-awake-asleep method, through a combined
      propofol/dexmedetomidine sedative infusion, to dexmedetomidine as the only
      sedation. Initial experience with the asleep-awake-asleep method in 2 patients
      was successful with the replacement of propofol/laryngeal mask anesthesia, 20 to
      30 minutes before ECoG testing, by dexmedetomidine infusion, maintained at 0.2
      mcg kg-1 h-1 throughout neurocognitive testing. Propofol anesthesia was
      reintroduced for resection. One patient received combined dexmedetomidine (0.2
      mcg kg-1 h-1) and propofol (200 mcg kg-1 min-1) infusions for sedation. Both
      infusions were stopped 15 minutes before ECoG. Subsequently, they were restarted
      and the epileptic foci resected. Three patients received dexmedetomidine as the
      sole sedative agent, together with scalp block local anesthesia, and incremental
      boluses totaling 150 to 175 mcg of fentanyl per case. Dexmedetomidine was started
      with 0.3 mcg kg-1 boluses and maintained with 0.2 to 0.7 mcg kg-1 h-1for
      craniotomy, testing, and resection. The infusion was paused for 20 minutes in 1
      patient to allow improvement in neurocognitive testing. This occurred within 10
      minutes. All patients enjoyed good hemodynamic control, with blood pressure
      maintained within 20% of initial values, and made uneventful recoveries. The
      surgical conditions were all reported as favorable. Dexmedetomidine can be used
      singly for sedation in awake craniotomy requiring ECoG. Individual dose ranges
      vary, but a bolus of 0.3 mcg kg-1 with an infusion of 0.2 mcg kg-1 min-1 is a
      good starting point, allowing accurate mapping of epileptic foci and subsequent
      resection.

PMID- 17198100
TI  - Manually controlled total intravenous anesthesia augmented by electrophysiologic
      monitoring for complex stereotactic neurosurgical procedures.
AB  - Stereotactically guided procedures are performed for an ever extending range of
      conditions. They present a unique anesthetic challenge. In our institution, a
      standardized anesthetic protocol for total intravenous anesthesia (TIVA)
      augmented by electrophysiologic monitoring with BIS or AEP monitors was
      introduced. We conducted a retrospective study of 21 patients (ASA status 2-3)
      presenting for stereotactically guided procedures who were anesthetized according
      to the protocol. Median duration of anesthesia was 260 minutes (222 to 325 min);
      on average 3.0 (1.0 to 4.2) adjustments to the TIVA-protocol were made per
      patient. Highest and lowest mean arterial blood pressures in relation to
      baselines were 100% (87.5% to 109.8%) and 68.7% (64.0% to 72.6%), respectively.
      Likewise highest and lowest heart rates recorded were 106.7% (98.5% to 119.0%)
      and 75.0% (68.2% to 83.3%). After discontinuation of TIVA, spontaneous breathing
      returned after 5.0 minutes (4.0 to 8.0 min), extubation was possible after 6.0
      minutes (5.0 to 10.0 min) and patients were ready for discharge to the ward after
      15.0 minutes (12.0 to 18.0 min). There were no cases of postoperative nausea or
      vomiting. We found that manually controlled TIVA, augmented by electrophysiologic
      monitoring, facilitated maintenance of an appropriate depth of anesthesia with
      stable hemodynamics and excellent recovery times.

PMID- 17198105
TI  - Increases in response entropy to skull pin insertion during neurosurgery.

PMID- 17198101
TI  - Bispectral index profile during carotid cross clamping.
AB  - This study aimed at investigating the Bispectral Index (BIS) profile during
      carotid cross clamping (CXC). The study involved a pilot group of 10 patients
      undergoing routine carotid endarterectomy with shunt insertion under total
      intravenous anesthesia, and a study group of 26 additional patients. In all
      patients, rates of propofol and remifentanil providing a steady-state level of
      hypnosis (BIS: 40-60) were maintained constant throughout a recording period
      ranging from 3 minutes before CXC to shunt insertion. BIS was recorded throughout
      this period and the internal carotid backflow observed at the time of shunt
      insertion was graded as good, moderate, or poor. In addition, A-Line
      Autoregressive Index (AAI) and processed electroencephalogram (EEG) parameters
      were recorded in patients of the study group. All parameters were averaged over 1
      minute before CXC, at CXC, 1, 2, and 3 minutes after CXC, and at shunt insertion.
      Statistical analysis was performed using chi2, Friedman, and Spearman correlation
      tests. For technical reasons, reliable AAI, BIS monitor-derived, and other
      processed EEG data were obtained in 24, 25, and 18 patients of the study group,
      respectively. During the first 3 minutes after CXC, BIS increased over 60 [68.8
      (6.1)] in 47%, decreased below 40 [34.9 (4.4)] in 25%, and remained in the 40 to
      60 range in 28% of all recruited patients. A BIS increase was more frequently
      observed in patients with moderate or poor than in those with good internal
      carotid backflow (78, 67, and 29%, respectively). It was significantly correlated
      to an increase in AAI and EEG amplitude, a decrease in EEG suppression ratio, and
      a shorter time between induction of anesthesia and CXC. A BIS decrease was
      significantly correlated to an increase in suppression ratio and a longer time
      between induction and CXC. In conclusion, during CXC under a constant level of
      intravenous anesthesia, BIS may increase, decrease, or remain unchanged. The
      paradoxical BIS increase could be related to borderline ischemia, a change in
      brain anesthetic agent concentration, or a change in the nociceptive
      antinociceptive balance associated with a CXC-elicited painful stimulation.
      Caution should be used when interpreting BIS value during CXC.

PMID- 17198106
TI  - Recurrent stridor due to raised intracranial pressure after meningitic
      hydrocephalus.

PMID- 17198112
TI  - Reaping benefits from intellectual capital.
AB  - The wealth and value of organizations are increasingly based on intellectual
      capital. Although acquiring talented individuals and investing in employee
      learning adds value to the organization, reaping the benefits of intellectual
      capital involves translating the wisdom of employees into reusable and sustained
      actions. This requires a culture that creates employee commitment, encourages
      learning, fosters sharing, and involves employees in decision making. An
      infrastructure to recognize and embed promising and best practices through social
      networks, evidence-based practice, customization of innovations, and use of
      information technology results in increased productivity, stronger financial
      performance, better patient outcomes, and greater employee and customer
      satisfaction.

PMID- 17198113
TI  - Rethinking traditional methods for measuring intellectual capital.
AB  - Historically, approaches to measuring intellectual capital have included both
      conventional accounting-based measures, such as variants of the market-to-book
      ratio, and more progressive measures, such as the measurement of intangible
      assets found in approaches such as the Balanced Scorecard and Human Resource
      Accounting. As greater emphasis is placed on intellectual capital and its various
      aspects in the continually growing service and knowledge economy, the use of
      assessment instruments to inventory the alignment, balance, and variety of
      intellectual capacities and metrics that assess the effectiveness of succession
      planning may represent new directions in which organizations can head in the
      measurement of this important construct.

PMID- 17198107
TI  - Prolonged propofol infusions in pregnant neurosurgical patients.

PMID- 17198115
TI  - Mentoring and its impact on intellectual capital: through the eyes of the mentee.
AB  - Recently, the concept of mentoring, and the use of mentorship programs, is being
      touted as a strategic means within healthcare organizations to address the
      nursing shortage that promises to continue well into the future. Mentoring, on
      the surface, could also be considered as an excellent means of supporting the
      development and retention of intellectual capital and succession planning within
      nursing. However, without a better understanding of the concept of mentoring,
      nurse leaders can never really know the full impact of mentoring in order to
      achieve such goals within the organization. Several key results from a study of
      mentorship in nursing support the concept of ongoing knowledge sharing within the
      discipline, as seen through the eyes of the mentee. The implications for nurse
      leaders shift the focus from formal mentoring programs to the creation of
      practice settings that foster the development of mentoring relationships.

PMID- 17198114
TI  - Managing the threat of lost knowledge through technology and teamwork.

PMID- 17198116
TI  - A systems approach to purchasing and implementing new technology.
AB  - There are many risks associated with purchasing and implementing new technology.
      The challenge is to reduce these risks to gain maximum benefit from the new
      technology purchased. In the high-cost world of healthcare, there is little room
      for wasting time and money related to technology implementation. If the workflow
      of the current system is not adequately understood before purchasing and
      implementing a new technology, that technology may mask underlying problems
      and/or create new ones. The purpose of this article is to present a framework for
      analyzing the current process or system, identifying the strengths and the areas
      in need of improvement. A thorough understanding of the problems with the current
      system and the barriers to change is necessary to ensure the selection of the
      "right" technology and promote its implementation.

PMID- 17198117
TI  - Nursing leadership succession planning in Veterans Health Administration:
      creating a useful database.
AB  - An electronic database was developed for succession planning and placement of
      nursing leaders interested and ready, willing, and able to accept an assignment
      in a nursing leadership position. The tool is a 1-page form used to identify
      candidates for nursing leadership assignments. This tool has been deployed
      nationally, with access to the database restricted to nurse executives at every
      Veterans Health Administration facility for the purpose of entering the names of
      developed nurse leaders ready for a leadership assignment. The tool is easily
      accessed through the Veterans Health Administration Office of Nursing Service,
      and by limiting access to the nurse executive group, ensures candidates
      identified are qualified. Demographic information included on the survey tool
      includes the candidate's demographic information and other
      certifications/credentials. This completed information form is entered into a
      database from which a report can be generated, resulting in a listing of
      potential candidates to contact to supplement a local or Veterans Integrated
      Service Network wide position announcement. The data forms can be sorted by
      positions, areas of clinical or functional experience, training programs
      completed, and geographic preference. The forms can be edited or updated and/or
      added or deleted in the system as the need is identified. This tool allows
      facilities with limited internal candidates to have a resource with Department of
      Veterans Affairs prepared staff in which to seek additional candidates. It also
      provides a way for interested candidates to be considered for positions outside
      of their local geographic area.

PMID- 17198118
TI  - Strength in nursing leadership: the key to the evolution of intellectual capital
      in nursing.
AB  - Intellectual capital, what does it mean? After reading several articles on the
      subject, I found the perfect definition by Leif Edvinsson, the chief architect
      behind a dynamic and holistic reporting model. According to the model, the hidden
      factors of human and structural capital, everything that gets left behind when
      the employee goes home added together comprises intellectual capital. "Human
      Capital is defined as the combined knowledge, skill, innovativeness, and ability
      of the company's individual employees to meet the task at hand. It also includes
      the company's values, culture, and philosophy. Human capital cannot be owned by
      the company" (Bontis N. Assessing knowledge assets: a review of the models used
      to measure intellectual capital. Int J Manag Rev. 3(1):41-60). Today there seems
      to be an extraordinary value being placed on what people know, and yet knowing
      doesn't always translate into action. The action most often occurs when social
      connections are strong and numerous so that trust is built and information flows.
      This article will address how nursing leadership is critical to unleashing the
      human capital inside every staff nurse.

PMID- 17198119
TI  - Coaching: a different approach to the nursing dilemma.
AB  - While the current nursing shortage continues, many new approaches from sign-on
      bonuses to "fast track training" are being suggested and implemented to
      ameliorate the situation. Yet, even with these expanded opportunities turnover is
      still too high. Recent studies suggest embedded factors called fit, links, and
      sacrifice exist between the employer and employees including nurses that account
      for current employees staying on their job. Creating a better understanding of
      embedded issues and creating an open but confidential environment to deal with
      conflict issues and job problems is suggested as a way to reduce turnover. A
      specific issue such as an unfavorable job assignment or more complex issues such
      as unmet expectations can cause conflict and job dissatisfaction. It is suggested
      that a coaching model can be used to understand the issues that create conflict
      and provide a method for resolution of job dissatisfaction.

PMID- 17198120
TI  - Evaluating an innovative program to improve new nurse graduate socialization into
      the acute healthcare setting.
AB  - PROBLEM: New nurse graduates experience a stressful role transition into
      healthcare organizations, with 30% leaving their first job within 1 year and 57%
      leaving by 2 years of employment. AIM: This study tests whether an internship
      program, Social and Professional Reality Integration for Nurse Graduates
      (SPRING), improves new nurse graduate retention, sense of belonging,
      organizational commitment, and anticipated turnover. DESIGN: Quasi-experimental,
      posttest only, control group design. METHOD: New nurse graduates hired by an
      academic institution that completed SPRING were compared with baseline nurse
      graduates who did not complete SPRING, using the Organizational Commitment
      Questionnaire, Modified Hagerty-Patusky Sense of Belonging Instrument, and
      Anticipated Turnover Scale. Retention was also examined. RESULTS: Anticipated
      Turnover was higher for baseline nurses than for 6-month SPRING nurses. Six-month
      SPRING nurses have lower antecedent sense of belonging than baseline or 12-month
      SPRING nurses. One-year retention is higher for SPRING new graduates than for non
      SPRING new graduates. CONCLUSION: Internship programs for nurse graduates must
      support the socialization of nurses and their transition into the professional
      role as well as teach the skills and knowledge needed for competence. This study
      supports the value of a comprehensive program for new nurse graduates in
      improving nurse retention and decreasing new nurse graduate intent to leave the
      organization at 6 months.

PMID- 17198121
TI  - Nurses organizational commitment: the discriminating power of gender.
AB  - The study of the organizational commitment has risen interest within the
      organization's researchers, who have been trying to understand the intensity and
      stability of the individual's dedication to the organization. The interest that
      this construct has raised is based on the idea of the existence of an association
      of the organizational commitment with variables considered important to the
      increase of the organizational effectiveness and productivity. The aim of this
      article is to describe organizational commitment, in its affective, normative,
      and continuance dimensions, from nurse practitioners, and to analyze the
      differences of that commitment regarding gender. Data were collected by
      questionnaire. The sample is constituted by nurse practitioners who develop their
      professional activity in 6 Portuguese hospitals. Data were analyzed using means,
      standard deviation, and independent samples t test. The sample consists of 1201
      nurses. The organizational commitment of the studied nurses is, on average,
      2.87+/-0.69 (in 5-point scale). When we make an analysis regarding gender, we
      verify that the organizational commitment is higher in women, being the
      difference statistically significant (t = -2.07; P < .05). There are different
      levels of commitment in male and female nurses, and it is higher in all
      dimensions in female nurses; however, the difference is only significant to the
      organizational and continuance commitment.

PMID- 17198122
TI  - The relationship between supervisor support and registered nurse outcomes in
      nursing care units.
AB  - Workplace social support is a major characteristic related to the Job Demand
      Control model of job stress. Organizational and managerial support have an effect
      on nurse satisfaction and burnout. The relationships between perceived supervisor
      support and measures of nurse occupation-related outcomes were investigated in 3
      nursing units within an academic medical center. Nurses with greater levels of
      perceived supervisor support experienced more positive job outcomes and less
      negative outcomes, including less occupational stress, than nurses with less
      perceived supervisor support. Implications for refocusing the role of the nurse
      supervisor and its effect on multiple nursing occupation-related outcomes are
      discussed.

PMID- 17198123
TI  - Caregivers: the intellectual capital of healing.
AB  - This article helps you to make a distinction that CARING not only fits under the
      classification of intellectual capital but is also one of the most valuable
      assets a healthcare organization can have. It takes this basic concept, which is
      often seen as soft, or even ignored by some, and ties it into the success of the
      future healthcare system.

PMID- 17198125
TI  - Securing intellectual capital by using scope of practice.

PMID- 17198138
TI  - New pain management options: drugs.

PMID- 17198139
TI  - Prevent fires when using oxygen cylinder regulators.

PMID- 17198124
TI  - Information technology: building nursing intellectual capital for the information
      age.
AB  - Healthcare is evolving from a task-based industry to a knowledge-based one. To
      gain and retain value as intellectual capital, nursing likewise must evolve from
      a vocation of task performers to a profession of knowledge-workers. Information
      technology can transform nursing tasks into nursing knowledge.

PMID- 17198140
TI  - Assisting with lumbar puncture.

PMID- 17198141
TI  - Untangling the complexities of male infertility.

PMID- 17198142
TI  - Trouble with birthin' babies.

PMID- 17198149
TI  - Get familiar with glucosamine.

PMID- 17198159
TI  - Responding to primary brain tumour.

PMID- 17198161
TI  - Salute to Sarge.

PMID- 17198162
TI  - Inhaled insulin: breathing new life into diabetes therapy.

PMID- 17198163
TI  - Teach your patient to administer: inhaled insulin.

PMID- 17198164
TI  - Patient education. Mitral valve prolapse.

PMID- 17198167
TI  - Good communication: finding the middle ground.

PMID- 17198165
TI  - Nurse/physician relationships: improving or not?

PMID- 17198168
TI  - Managing acute acetaminophen toxicity.

PMID- 17198174
TI  - Understanding palliative wound care.

PMID- 17198175
TI  - Simple steps to stamp out vitamin B12 deficiency.

PMID- 17198176
TI  - Documenting culturally competent psychosocial nursing diagnoses.

PMID- 17198178
TI  - Hydrofluoric acid exposure.

PMID- 17198179
TI  - Acute pancreatitis: animal models and recent advances in basic research.
AB  - Acute pancreatitis (AP) is characterized by edema, acinar cell necrosis,
      hemorrhage, and severe inflammation of the pancreas. Patients with AP present
      with elevated blood and urine levels of pancreatic digestive enzymes, such as
      amylase and lipase. Severe AP may lead to systemic inflammatory response syndrome
      and multiorgan dysfunction syndrome, which account for the high mortality rate of
      AP. Although most (>80%) cases of AP are associated with gallstones and
      alcoholism, some are idiopathic. Although the pathogenesis of AP has not yet been
      elucidated, a common feature is the premature activation of trypsinogen within
      pancreatic tissues, which triggers autodigestion of the gland. Recent advances in
      basic research suggest that etiologic factors including cyclooxygenase-2,
      substance P, and angiotensin II may have novel roles in this disease. Basic
      research data obtained thus far have been based on animal models of AP ranging
      from mild edematous pancreatitis to severe necrotizing pancreatitis. In view of
      this, an adequate selection of experimental animal models is of paramount
      importance. Notwithstanding these animal models, it should be emphasized that
      none of these models mimic the clinical situation where varying degrees of
      severity usually occur. In this review, commonly used animal models of AP will be
      critically evaluated. A discussion of recent advances in our knowledge about AP
      risk factors is also included.

PMID- 17198180
TI  - Coagulation, platelets, and acute pancreatitis.
AB  - Acute pancreatitis generates a complex cascade of immunological events that
      affect the pathogenesis and the progression of this disease. Several inflammatory
      mediators seem to play a critical role in the pathogenesis of pancreatitis and
      the subsequent inflammatory response. In turn, these mediators can influence
      hemostasis. Coagulation abnormalities occur in acute pancreatitis and are related
      to its severity. The contribution of blood platelets in the disturbed hemostasis
      in acute pancreatitis, although extensively studied, remains obscure. This
      article reviews the local and systemic implications of hemostatic abnormalities
      during acute pancreatitis. Furthermore, we discuss the prognostic value and the
      potential therapeutic implications of platelet activation and other hemostatic
      variables.

PMID- 17198181
TI  - Does endoscopic therapy favorably affect the outcome of patients who have
      recurrent acute pancreatitis and pancreas divisum?

PMID- 17198182
TI  - Dysfunction of the pancreas in healthy smoking persons and patients with chronic
      pancreatitis.
AB  - OBJECTIVES: The aim of the study was to assess the effect of cigarette smoking on
      the endocrine pancreatic function by determining the levels of serum glucose and
      plasma insulin as well as by defining immunohistochemical localization of insulin
      and glucagon in tissue specimens of the pancreata derived from healthy persons
      and smoking and nonsmoking patients with diagnosed chronic pancreatitis (CP).
      METHODS: The oxidative method was used to measure fasting glycemia in blood
      plasma and the method enzyme-linked immunoassay to determine the level of insulin
      in plasma. Immunohistochemical localization of hormones in paraffin tissue
      specimens of the pancreas was performed using the LSAB2-HRP visual test with
      polyclonal insulin and glucagon antibodies. The intensity of immunohistochemical
      reaction was calculated with digital imaging methodology. RESULTS: The study
      revealed a substantially higher level of serum glucose in smoking CP patients and
      in healthy persons compared with nonsmoking patients and healthy persons, whereas
      insulin concentration in smoking patients was statistically lower than in
      nonsmokers. Smoking patients showed significantly lower expression of insulin and
      glucagon in the pancreas compared with nonsmoking patients and healthy persons.
      CONCLUSIONS: Impairment of the endocrine function of beta and alpha cells in the
      pancreatic islets is frequently manifested by complications in pancreatitis
      resulting among others from long-term smoking.

PMID- 17198183
TI  - K-ras mutation and p16 and preproenkephalin promoter hypermethylation in plasma
      DNA of pancreatic cancer patients: in relation to cigarette smoking.
AB  - OBJECTIVES: To examine the profiles of K-ras mutations and p16 and
      preproenkephalin (ppENK) promoter hypermethylation and their associations with
      cigarette smoking in pancreatic cancer patients. METHODS: In plasma DNA of 83
      patients with untreated primary pancreatic ductal adenocarcinoma, DNA
      hypermethylation was determined by methylation-specific polymerase chain reaction
      and K-ras codon 12 mutations by enriched-nested polymerase chain reaction
      followed by direct sequencing. Information on smoking exposure was collected by
      in-person interview. Pearson chi test and Fisher exact test were used in
      statistical analysis. RESULTS: K-ras mutations, ppENK, and p16 promoter
      hypermethylation were detected in 32.5%, 29.3%, and 24.6% of the patients,
      respectively. Sixty-three percent (52/83) of patients exhibited at least one of
      the alterations. Smoking was associated with the presence of K-ras mutations (P =
      0.003). A codon 12 G-to-A mutation was predominantly observed in regular smokers
      and in heavy smokers (pack-year of smoking > or =36). Smoking was not associated
      with p16 or ppENK hypermethylation. CONCLUSIONS: These preliminary observations
      suggest that plasma DNA might be a useful surrogate in detecting genetic and
      epigenetic alterations of pancreatic cancer. The findings on the association
      between K-ras mutation and smoking were in consistency with previous studies.
      Further studies on environmental modulators of epigenetic changes in pancreatic
      cancer are warranted.

PMID- 17198184
TI  - Incidence of alcoholic pancreatitis in Japanese alcoholics: survey of male
      sobriety association members in Japan.
AB  - OBJECTIVE: To estimate the incidence of alcoholic pancreatitis, a dependence
      questionnaire survey was administered to male members of the sobriety association
      in Japan. METHODS: Questionnaires asking about age, age at start of alcohol
      drinking, amount of alcohol consumption, duration of drinking, the initiated age
      of abstinence, medical history of pancreatitis, the age at diagnosis of
      pancreatitis, and the etiology of pancreatitis were sent to 7876 male members of
      a sobriety association in Japan. RESULTS: Of 4120 members who replied to the
      questionnaire, 857 (20.8%) had a medical history of pancreatitis. Of these 857
      members, 418 (10.1%) had been diagnosed with alcoholic pancreatitis, 32 (0.8%) as
      gallstone pancreatitis, and 407 (9.9%) with unknown etiology or etiology
      forgotten. A clear history of pancreatitis and information on habitual heavy
      drinking and the consumed amount of alcohol could be obtained from 373 of the 418
      members diagnosed with alcoholic pancreatitis and from 345 of the 407 members
      with pancreatitis of unknown etiology. These 718 respondents were considered to
      be true alcoholic pancreatitis cases, with an extrapolated incidence of 9.1%
      (718/7876) to 17.4% (718/4120) cases of alcoholic pancreatitis in alcoholics in
      Japan. Alcoholics with a history of pancreatitis began drinking at relatively
      younger age and consumed a significantly greater amount of alcohol per day
      compared with 3113 alcoholics without a medical history of pancreatitis.
      CONCLUSION: This survey suggests that the incidence of alcoholic pancreatitis in
      alcoholics is much higher than previously reported.

PMID- 17198185
TI  - Comparison and validation of scoring systems in a cohort of patients treated for
      biliary acute pancreatitis.
AB  - OBJECTIVES: There are a few prospective studies assessing the severity of acute
      pancreatitis with exclusive criteria for biliary etiology. The aim of this study
      was to assess the reliability of prediction of the severity and mortality of
      acute biliary pancreatitis by using the Ranson, Acute Physiology And Chronic
      Health Evaluation II and III, Simplified Acute Physiology Score II, and Mortality
      Probability Model (MPM) II systems. METHODS: Fifty-eight patients with acute
      biliary pancreatitis were studied prospectively. Disease severity scores and
      mortality predictions were calculated using the collected data in the first 24
      hours of admission and for Ranson score in the first 48 hours. Discrimination and
      calibration characteristics of each system were determined by using area under
      receiver operating characteristics curve and Hosmer-Lemeshow goodness-of-fit
      test, respectively. RESULTS: Among 58 patients included, there were 4 mortalities
      (6.8%). Fifteen patients (25.8%) had severe disease, and 5 patients (8.6%) had
      systemic and local complications. All systems had reliable power of
      discrimination and calibration. Among systems tested MPM II was the best
      performing as far as discrimination, and calibration characteristics are
      considered. The items of MPM II that were positive in patients with severe
      pancreatitis were those related to systemic perfusion. CONCLUSIONS: Mortality
      Probability Model II predicted mortality at admission is better than the other
      systems in predicting the severity of pancreatitis. Results also indicate the
      important role of systemic perfusion at the early phases of acute pancreatitis in
      the progression of disease.

PMID- 17198186
TI  - Comparison of pancreas juice proteins from cancer versus pancreatitis using
      quantitative proteomic analysis.
AB  - OBJECTIVES: Pancreatitis is an inflammatory condition of the pancreas. However,
      it often shares many molecular features with pancreatic cancer. Biomarkers
      present in pancreatic cancer frequently occur in the setting of pancreatitis. The
      efforts to develop diagnostic biomarkers for pancreatic cancer have thus been
      complicated by the false-positive involvement of pancreatitis. METHODS: In an
      attempt to develop protein biomarkers for pancreatic cancer, we previously use
      quantitative proteomics to identify and quantify the proteins from pancreatic
      cancer juice. Pancreatic juice is a rich source of proteins that are shed by the
      pancreatic ductal cells. In this study, we used a similar approach to identify
      and quantify proteins from pancreatitis juice. RESULTS: In total, 72 proteins
      were identified and quantified in the comparison of pancreatic juice from
      pancreatitis patients versus pooled normal control juice. Nineteen of the juice
      proteins were overexpressed, and 8 were underexpressed in pancreatitis juice by
      at least 2-fold compared with normal pancreatic juice. Of these 27 differentially
      expressed proteins in pancreatitis, 9 proteins were also differentially expressed
      in the pancreatic juice from pancreatic cancer patient. CONCLUSIONS:
      Identification of these differentially expressed proteins from pancreatitis juice
      provides useful information for future study of specific pancreatitis-associated
      proteins and to eliminate potential false-positive biomarkers for pancreatic
      cancer.

PMID- 17198187
TI  - Does moderate celiac axis stenosis identified on preoperative multidetector
      computed tomographic angiography predict an increased risk of complications after
      pancreaticoduodenectomy for malignant pancreatic tumors?
AB  - OBJECTIVES: To identify any association between celiac artery compromise found on
      computed tomographic angiography and the incidence of postoperative and
      perioperative complications. METHODS: The computed tomographic angiograms of 36
      patients who underwent the Whipple procedure for pancreatic adenocarcinoma were
      examined retrospectively. The association between the results and surgical course
      was investigated. RESULTS: Twelve patients (33%) had significant postoperative
      complications. Ten (28%) had evidence of celiac artery stenosis. Stenosis ranged
      from 20% to 60%. There was no evidence of a difference between the 2 groups.
      CONCLUSION: There seems to be no evidence of an increased risk of postoperative
      or perioperative complication in patients undergoing the Whipple procedure, with
      a celiac stenosis of up to 60%.

PMID- 17198188
TI  - Different patterns of p16INK4A and p53 protein expressions in intraductal
      papillary-mucinous neoplasms and pancreatic intraepithelial neoplasia.
AB  - OBJECTIVES: To examine aberrations and differences of cell cycle regulatory
      proteins between intraductal papillary-mucinous neoplasms (IPMNs) and pancreatic
      intraepithelial neoplasias (PanINs). METHODS: In total, 47 IPMN lesions and 42
      PanIN lesions were obtained from 26 patients with IPMN and 16 patients who
      underwent pancreatic surgery for invasive pancreatic ductal cancer or other
      diseases. They were subjected to conventional hematoxylin-eosin staining and
      immunostaining for p16INK4A and p53. The percentages of immunohistochemical
      positivity or negativity were compared between IPMN and PanIN, in accordance with
      the same histological grade of atypia. The Ki-67 labeling index was also counted
      in each lesion. RESULTS: Either the loss of p16INK4A expression or the
      overexpression of p53 was much more frequently observed among PanIN-3 than among
      carcinoma in situ in IPMN (P = 0.046 and 0.008, respectively). The Ki-67 labeling
      index was correlated with the histological grades of both PanINs and IPMNs (P =
      0.0001 and P = 0.0001, respectively). CONCLUSIONS: There are different
      immunohistochemical expression patterns of p16INK4A and p53 between IPMNs and
      PanINs. These may substantiate their different genetic progressions to invasive
      carcinoma.

PMID- 17198189
TI  - Diagnosis and treatment of pancreatoblastoma in China.
AB  - OBJECTIVES: Pancreatoblastoma is an extremely rare pancreatic neoplasm. The aims
      of the current study were to analyze the clinical, pathological, and
      immunohistochemical features of pancreatoblastoma and to discuss its management.
      METHODS: The clinical data of 30 Chinese pancreatoblastoma patients (among them,
      1 case was treated by authors, and the other 29 cases were reported in Chinese
      literature from January 1981 to December 2005) were reviewed and analyzed.
      RESULTS: Patients with pancreatoblastoma had an age range of 5 months to 42
      years. There were 24 children and 6 adult cases, with a male-female ratio of 2:1
      (20/10). The tumor size ranged from 2 to 20 cm in diameter. Metastases were found
      during the operation in 8 cases (26.7%) (among them, 66% with liver invasion and
      50% with multiple metastases including spleen, kidney, and bone).
      Pancreatoduodenectomy was performed in 5 cases (16.7%). Nine cases (30%) received
      chemotherapy with vincristine, cyclophosphamide, and adriamycin. By
      immunohistochemistry, the tumors exhibited acinar, endocrine, and ductal
      differentiation. The mean time of survival was 25.5 months. CONCLUSIONS: These
      results suggest that the diagnosis of pancreatoblastoma mainly depends on the
      pathological findings, surgical resection is the most effective way for cure, and
      adjuvant chemotherapy could be a good palliative method in certain patients.

PMID- 17198190
TI  - Pancreatographic investigation of embryology of complete and incomplete pancreas
      divisum.
AB  - OBJECTIVES: To investigate embryology of complete and incomplete pancreas divisum
      (PD). METHODS: We analyzed anatomy of the pancreatic duct system in 44 cases of
      complete PD and 41 cases of incomplete PD. Under the concept of branch fusion
      between the ventral and dorsal pancreatic ducts, incomplete PD was divided into 3
      types: fusion of the extreme end of the upper branch of the ventral pancreatic
      duct with the dorsal pancreatic duct (type 1); fusion of the lower branch of the
      dorsal pancreatic duct with the lower branch of the ventral pancreatic duct (type
      2); and fusion of the lower branch of the dorsal pancreatic duct with the ventral
      pancreatic duct (type 3). RESULTS: Complete PD showing no ventral pancreatic duct
      radiologically might be induced by complete regression of the ventral pancreatic
      duct near the orifice in the pancreas with communication between the ventral and
      dorsal pancreatic ducts. Embryological mechanism of incomplete PD (type 1, n =
      16; type 2, n = 10; and type 3, n = 15) was confirmed by measurement in
      pancreatograms. CONCLUSIONS: Some cases of complete PD might be induced by
      complete regression of the ventral pancreatic duct near the orifice. Embryology
      of incomplete PD can be accounted by concept of branch fusion.

PMID- 17198191
TI  - Intramuscular injection of islet neogenesis-associated protein peptide stimulates
      pancreatic islet neogenesis in healthy dogs.
AB  - OBJECTIVES: Diabetes is a serious health problem. It has been proposed that islet
      neogenesis from pancreatic progenitor cells may restore insulin secretion in
      diabetic mammals. Islet neogenesis- associated protein (INGAP) stimulates islet
      neogenesis; therefore, we hypothesized that it would stimulate islet neogenesis
      in dogs. METHODS: Forty nondiabetic beagle dogs were randomly divided into 4
      groups. Group 1 received daily intramuscular injections of vehicle, whereas the
      other 3 groups received daily INGAP injections of 0.5, 1.5, or 10 mg/kg. After 30
      days, pancreatic tissues were collected, and RNA and histological sections were
      analyzed. RESULTS: In dogs treated with 1.5 mg/kg INGAP, there was a significant
      (P < 0.001) increase in the percentage of insulin-positive cells (P < 0.001) and
      insulin gene expression. There was a trend to increased insulin-positive cells
      and gene expression with treatments of 0.5 and 10 mg/kg peptide. Protein gene
      product 9.5-positive cells were increased with treatment. CONCLUSIONS: These
      results indicate that INGAP stimulates cells in the pancreatic duct epithelium of
      healthy dogs (putative islet progenitor cells) to develop along a neuroendocrine
      pathway and form new islets in response to INGAP peptide. The INGAP might be an
      effective therapy for diabetes.

PMID- 17198192
TI  - Effects of continuous high-volume hemofiltration on experimental severe acute
      pancreatitis in pigs.
AB  - OBJECTIVE: To compare the effects of different doses of hemofiltration on severe
      acute pancreatitis (SAP) in pigs. METHODS: The animal model of SAP was produced
      by intraductal injection of sodium taurocholate and trypsin. Animals in group 1
      served as SAP control. Animals in group 2 received (20 mL/kg per hour) continuous
      low-volume hemofiltration (LVHF), and animals in group 3 received (100 mL/kg per
      hour) continuous high-volume hemofiltration (HVHF) immediately after the
      induction of SAP. After the instrumentation of the animals by arterial and Swan
      Ganz catheters, hemodynamic indexes were monitored intermittently at different
      times. The rectal temperature and the concentration of amylase and cytokines in
      serum were measured at the same time. RESULTS: The survival time of HVHF group
      was significantly prolonged (P < 0.01). The initial elevation of body temperature
      and the hypothermia in the late course of experiments were significantly
      ameliorated by HVHF (P < 0.01). Six hours after the induction of pancreatitis,
      the urine output of animals in HVHF group was obviously higher than that in
      control group (P < 0.05), which stayed behind 36 hours later (P < 0.05). The
      major hemodynamic finding was that pancreatitis-induced hypotension was
      significantly attenuated by HVHF (P < 0.01). The development of hyperdynamic
      circulatory failure was simultaneously attenuated, as reflected by a limited
      increase in CI, an attenuated decrease in systemic vascular resistance index.
      Plasma amylases in the HVHF group were significantly lower than those in control
      and LVHF groups (P < 0.01). The serum concentrations of cytokines such as tumor
      necrosis factor alpha (TNF-alpha), interleukin (IL) 6, and IL-10 all decreased
      significantly in treatment groups (P < 0.01), and those of HVHF group were less
      significant than the HVHF group (P < 0.01). CONCLUSIONS: The HVHF was associated
      with a better hemodynamic profile, a less hyperkinetic state, and more prolonged
      survival than that of LVHF, which may result from the HVHF that can remove the
      inflammatory cytokines more efficiently.

PMID- 17198193
TI  - Anatomical and histological observation on the pancreas in adult zebrafish.
AB  - OBJECTIVES: To investigate the anatomic structure of the pancreas and the
      distribution of the islets in adult zebrafish. METHODS: In situ immunofluorescent
      staining, electron microscopy, and serial paraffin-embedded sectioning with
      hematoxylin/eosin staining were applied. RESULTS: The pancreas along the
      intestine included 4 relatively independent and concentrated lobes, in which 4
      kinds of islets-principal islets, Brockmann bodies, diffusely existing islets,
      and single beta-cell-were observed. Some islets contained both alpha and beta
      cells, whereas some contained only beta cells. The islet number in each adult
      zebrafish averaged 84.53 +/- 43.77; and the lower quartile, median, and upper
      quartile were 55.25, 70.50, and 112.00, respectively (n = 40). The different
      islets were differently distributed in the 4 pancreatic lobes with statistical
      significance (P < 0.05). Meanwhile, 3 kinds of secretory granules were found in
      the cytoplasm of different islet cells. CONCLUSIONS: According to the distinct
      distribution, concentration of the pancreas, and different contents of the islets
      within the pancreas, 4 lobes of the pancreas along the intestine-the gallbladder
      spleen lobe, the middle lobe, the left lobe, and the ventral lobe-were identified
      in adult zebrafish.

PMID- 17198194
TI  - Matrix metalloproteinase-3 secretion from human pancreatic periacinar
      myofibroblasts in response to inflammatory mediators.
AB  - OBJECTIVES: Matrix metalloproteinases (MMPs) play roles in the pathophysiology of
      pancreatic disorders. However, the regulation of MMP-3 secretion in the pancreas
      remains unclear. In this study, we assessed the expression of MMP-3 in human
      pancreatic periacinar myofibroblasts. METHODS: MMP-3 secretion and MMP-3 mRNA
      expression were determined by enzyme-linked immunosorbent assay and real-time
      polymerase chain reaction, respectively. RESULTS: In human pancreatic
      myofibroblasts, MMP-3 secretion and mRNA expression were induced by interleukin
      (IL)-17, IL-1beta, and tumor necrosis factor (TNF) -alpha, respectively. The
      effects of IL-17 were detected as similar in extent to those induced by IL-1beta
      or TNF-alpha. Costimulation by IL-17 plus IL-1beta and/or IL-17 plus TNF-alpha
      induced a synergistic increase in MMP-3 secretion, although the costimulatory
      effects of these combinations were not detected in tissue inhibitor of matrix
      metalloproteinase-1 secretion. Adenovirus-mediated transfer of a stable form of
      IkappaBalpha markedly inhibited the effects of IL-17, IL-1beta, and TNF-alpha.
      Mitogen-activated protein kinase inhibitors (U0126, PD098059, and SB203580) also
      blocked MMP-3 secretion. These findings indicate a role for nuclear factor-kappaB
      and mitogen-activated protein kinases in cytokine-induced MMP-3 secretion.
      CONCLUSIONS: Pancreatic periacinar myofibroblasts actively secrete MMP-3 in
      response to IL-17, IL-1beta, and TNF-alpha. Pancreatic myofibroblasts may play an
      important role in extracellular matrix turnover via MMP-3 secretion in the
      pancreas.

PMID- 17198195
TI  - Beta-cell function in individuals carrying the mitochondrial tRNA leu (UUR)
      mutation.
AB  - OBJECTIVES: To assess the beta-cell function in individuals with mitochondrial
      DNA A3243G mutation with normal glucose tolerance (NGT) or diabetes mellitus
      (DM). Furthermore, in diabetic individuals, we evaluated the effect of coenzyme
      Q10 supplementation on insulin secretory response. METHODS: Eight mutation
      positive individuals with NGT (n = 4) or DM (n = 4) were studied. beta-Cell
      function was evaluated by C-peptide levels before and after a mixed liquid meal
      (Sustacal) challenge and by first-phase insulin response. RESULTS: Fasting and
      Sustacal-stimulated C-peptide levels were significantly lower in diabetic
      patients than that in controls (area under the curve: 104.1 +/- 75.7 vs 520.8 +/-
      173.8, P = 0.001), whereas in individuals with NGT, this response was preserved
      (area under the curve: 537.8 +/- 74.3 vs 520.8 +/- 179.8, P = 0.87). The duration
      of diabetes was negatively correlated with fasting C-peptide levels (r = -0.961,
      P = 0.038). Among the 3 patients with residual insulin secretion, the short-term
      treatment with coenzyme Q10 (3 months) improved C-peptide levels in 2 of them.
      The first-phase insulin response was diminished in 2 individuals with NGT, the
      oldest ones. CONCLUSIONS: We showed an impaired insulin secretory capacity in
      individuals carrying the A3243G mutation, this possibly being the primary defect
      contributing to the development of DM. In addition, our data suggest that this
      could be a functional defect.

PMID- 17198198
TI  - Cystic dystrophy of the duodenal wall developing in heterotopic pancreas: report
      of 9 cases.
AB  - OBJECTIVE: Cystic dystrophy in heterotopic pancreas (CDHP), an uncommon but
      serious complication of dilatation of the ectopic pancreatic ducts of heterotopic
      pancreatic tissue, occurs most often in the second part of the duodenum. This
      disorder is difficult to diagnose and raises various therapeutic questions. The
      aim of this study was to evaluate the most useful procedures for investigating
      suspected CDHP and to consider late results after surgical treatment by
      pancreaticoduodenectomy (PD). METHODS: This retrospective study concerned 9
      patients who developed CDHP of the duodenal wall during an 18-year period (1983
      2001). All patients were symptomatic and underwent PD (no postoperative deaths).
      Clinical presentation, imaging findings, pathological features, and follow-up
      were analyzed. RESULTS: All patients but one were male alcoholics (mean age, 48
      years; range, 37-63 years). The clinical presentation was abdominal pain (n = 9)
      associated with vomiting (n = 6), jaundice (n = 2), and weight loss (n = 9).
      Upper endoscopy (n = 9) showed nonspecific inflammatory lesions with duodenal
      stenosis (n = 4). Retrospective analysis of computed tomographic findings (n = 9)
      studied specific signs of CDHP and nonspecific inflammatory changes in
      periduodenal space. Endoscopic ultrasonography (n = 4) and magnetic resonance
      cholangiopancreatography (n = 2) were the most useful investigations.
      Pathological findings in surgical specimens were multiple cysts located in the
      thickened duodenal wall (n = 9), ectopic pancreatic tissue (n = 7), fibrosis of
      the normal gland (n = 4), and adenocarcinoma in ectopic tissue (n = 1). During
      the follow-up period, 4 patients died 12, 16, 48, and 72 months after PD. The
      cause of death was independent of CDHP or PD, but related to persistent
      alcoholism in 2 cases involving chronic pancreatitis. In 1 case, the patient died
      of disseminated adenocarcinoma. The other 5 patients had a good result.
      CONCLUSION: Endoscopic ultrasonography and magnetic resonance pancreatography are
      the most useful investigations for the diagnosis of CDHP. Pancreaticoduodenectomy
      is justified after failure of medical treatment or endoscopic drainage. Late
      results after PD are dependent on alcoholic consumption when CDHP is associated
      with chronic pancreatitis.

PMID- 17198197
TI  - Homocysteine-induced impairment of insulin secretion from clonal pancreatic BRIN
      BD11 beta-cells is not prevented by catalase.
AB  - OBJECTIVES: Although detrimental effects of homocysteine attributed to
      homocysteine auto-oxidation and generation of hydrogen peroxide (H2O2) have been
      reported in various cell types, such actions have not been considered in
      pancreatic beta-cells. This study investigates the acute effects of homocysteine
      on beta-cell integrity and regulation, in particular, the role of H2O2 generated
      by auto-oxidation. METHODS: Assessment of beta-cell function was examined during
      acute 20- or 40-minute incubations with homocysteine using clonal BRIN-BD11 beta
      cells. RESULTS: Homocysteine (50-1000 micromol/L) inhibited basal and glucose
      induced insulin secretion in a concentration-dependent manner. Insulinotropic
      responses to alanine, arginine, 2-ketoisocaproate, elevated Ca, tolbutamide,
      potassium chloride (KCl), forskolin, and phorbol 12-myristate 13-acetate were
      also significantly reduced by homocysteine. Likewise, preincubation with
      homocysteine caused a reduction in the insulinotropic responses to glucose and
      each of the secretagogues tested. Notably, excess catalase (100 microg/mL) in the
      buffer, although sufficient to remove homocysteine-derived H2O2, did not
      alleviate the detrimental effects of homocysteine. CONCLUSIONS: Collectively,
      these data suggest that homocysteine impairs insulin secretory function by
      mechanisms independent of H2O2 generation. Although homocysteine may give rise to
      reactive oxygen species, these observations indicate detrimental non-oxidative
      pancreatic beta-cell actions of homocysteine.

PMID- 17198196
TI  - Substance P mediates cerulein-induced pancreatic microcirculatory dysfunction in
      mice.
AB  - OBJECTIVES: The present study was conducted to examine the contribution of
      substance P to the pancreatic microcirculatory dysfunction during acute
      pancreatitis. METHODS: Pancreatitis was elicited by up to 6 hourly injections of
      cerulein (50 microg/kg IP) in male C57Bl/6 mice. At 0, 1, 3, and 6 hours after
      cerulein treatment, the pancreatic microvasculature in anesthetized mice was
      studied using established high-resolution in vivo microscopic methods. RESULTS:
      Treatment of mice with cerulein for 6 hours caused a 30% decrease in capillary
      perfusion and the diameter of the capillaries and an increase in microvascular
      permeability (20%) and interstitial space (30-fold). The administration of the
      substance P receptor antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11) (2 mg/kg IP)
      minimized the pancreatic microcirculatory dysfunction 3 hours after cerulein
      treatment. The superfusion of substance P for 0.5 hours decreased the diameter
      (by 22%) and increased microvascular permeability (by 23%) along with
      interstitial space (22-fold increase). Blockade of substance P receptor
      attenuated substance P-induced pancreatic microcirculatory dysfunction.
      CONCLUSIONS: These results suggest that substance P mediates pancreatic
      microcirculatory dysfunction during the development of acute pancreatitis.

PMID- 17198199
TI  - Adult-onset asthma and periocular xanthogranulomas in a patient with
      lymphoplasmacytic sclerosing pancreatitis.
AB  - The clinical syndrome of adult-onset asthma and periocular xanthogranulomas
      represents a rare systemic autoimmune disorder that has not been previously
      associated with autoimmune pancreatitis. Herein, we describe the case report of a
      61-year-old man with the unique clinical association of adult-onset asthma,
      atopy, and periocular xanthogranulomas, who had previously been diagnosed with
      lymphoplasmacytic sclerosing pancreatitis. We have previously reported the case
      of a patient with lymphoplasmacytic sclerosing pancreatitis that developed
      postoperative inflammatory pseudotumor of the orbit. These unique,
      extrapancreatic, ocular manifestations of this disease add to the published
      observations that it is a systemic disorder with the potential for multiorgan
      involvement that may have a spectrum of clinical manifestations that includes
      adult-onset asthma and periocular xanthogranulomas.

PMID- 17198200
TI  - Pancreatic cancer presenting as a Sister Mary Joseph's nodule: case report and
      update of the literature.
AB  - Cutaneous metastasis of an occult malignancy to the umbilicus has come to be
      known as a Sister Mary Joseph's nodule (SMJN). More than 400 cases of this well
      described clinical presentation of advanced gastrointestinal and gynecologic
      cancers have been reported. Pancreatic cancer presenting as a SMJN is a rare
      phenomenon. In most series, the pancreas is the source of a SMJN in 7% to 9% of
      cases. We report a case of pancreatic adenocarcinoma in which the initial
      presenting sign was a SMJN. We also reviewed the published literature from the
      last 100 years on this phenomenon by conducting a detailed PubMed search.
      Including this case, we identified 57 cases of SMJN originating from the
      pancreas. The clinical patient characteristics with regard to age, male-female
      ratio, race, and prognosis of these cases were similar to that of pancreatic
      cancer in general. In contrast, 91% of these cases originated in the tail and
      body of the pancreas rather than the head of the pancreas. This case emphasizes
      that pancreatic cancer should be considered in the differential diagnosis of
      umbilical metastasis.

PMID- 17198201
TI  - Outcome of the biliary acute pancreatitis is not associated with body mass index.

PMID- 17198203
TI  - Response to letter: colonic apple-core lesion resulting from cyberknife treatment
      of unresectable pancreatic cancer.

PMID- 17198204
TI  - Acute recurrent pancreatitis complicating hemobilia in a patient with
      hepatocellular cancer and recipient of anticoagulants successful treatment with
      metal stent placement (pancreatitis complicating hemobilia).

PMID- 17198206
TI  - Colocalization between beta-catenin and insulin suggests a novel role for the
      adherens junction in beta-cell function.

PMID- 17198207
TI  - An extension of pancreatic pseudocysts in the neck.

PMID- 17198208
TI  - Transitional medicine: will emergency medicine physicians be ready for the
      growing population of adults with congenital heart disease?
AB  - BACKGROUND: Currently, approximately 85% of children with significant congenital
      heart problems survive to adolescence and adulthood. This survival rate
      represents a dramatic improvement in the medical and surgical care of congenital
      heart disease (CHD) during the last 35 years. Nevertheless, these patients remain
      at increased risk for significant cardiac problems long after primary
      interventions are completed. They are more likely than the general population to
      seek urgent medical care, often in an emergency department setting. They
      represent a new and growing population of emergency department patients with a
      specialized set of problems not traditionally part of the training for emergency
      medicine (EM) physicians. OBJECTIVE: We investigated the current scope and status
      of training for EM physicians in the immediate management of CHD patients as they
      grow to adolescence and adulthood. METHODS: We conducted 2 cross-sectional
      surveys to assess the current training environment for 2 specific groups: (1) US
      general EM (GEM) residency programs, and (2) US and Canadian pediatric EM (PEM)
      fellowship programs. Surveys were mailed to program directors during the summer
      of 2005. A total of 198 surveys were sent out: 134 to GEM residency directors and
      64 to PEM fellowship directors. RESULTS: The response rate overall was 68%, with
      a 64% response rate from the GEM residency directors and 77% from the PEM
      fellowship directors. Across all programs, 43% (56/130 respondents) were "unsure"
      about the existence or location of an adult CHD (ACHD) clinic in their area. When
      asked to rate the importance of ACHD as a training topic, 40 (85%) of 47 PEM
      fellowship directors and 62 (74%) of 84 GEM residency directors ranked it as "low
      priority" or "unnecessary." However, 70 (55%) of 127 respondents were "unsure,"
      "uncomfortable," or "worried" about the ACHD training their trainees receive
      (PEM, 59%; GEM, 53%). In addition, most program directors (75%) estimated that
      their trainees care for 5 or fewer ACHD patients annually. CONCLUSIONS: There
      seems to be a mismatch between the growing need for ACHD emergency care and the
      current state of this topic in both GEM residency and PEM fellowship training
      programs.

PMID- 17198209
TI  - Pharmacologic treatment of acute pediatric methamphetamine toxicity.
AB  - OBJECTIVE: To report our experience with the use of benzodiazepines and
      haloperidol for sedation of pediatric patients with acute methamphetamine
      poisoning. METHODS: We performed a retrospective chart review of 18 pediatric
      patients who were admitted to an intensive care unit for methamphetamine toxicity
      from January 1997 to October 2004 and treated with benzodiazepines or
      haloperidol. Clinical features, dose of drug received, and laboratory test
      results were noted. Adverse effects from the use of haloperidol such as prolonged
      QTc, dystonic reactions, and torsades de pointes were recorded. RESULTS: Eighteen
      patients received a benzodiazepine, the dose of which varied depending on the
      agent used. Twelve patients also received parenteral haloperidol. No
      complications developed from the use of either haloperidol or benzodiazepines.
      CONCLUSIONS: In this case series of pediatric patients poisoned with
      methamphetamine, parenteral benzodiazepines and haloperidol were used to control
      agitation. No serious adverse effects were observed from the use of these agents.

PMID- 17198210
TI  - Single-dose oral dexamethasone in the emergency management of children with
      exacerbations of mild to moderate asthma.
AB  - OBJECTIVE: To compare the efficacy of a single dose of oral dexamethasone (Dex)
      versus 5 days of twice-daily prednisolone (Pred) in the management of mild to
      moderate asthma exacerbations in children. STUDY DESIGN: A prospective,
      randomized, double-blinded trial of children 2 to 16 years of age who presented
      to the emergency department (ED) with acute mild to moderate asthma
      exacerbations. Subjects received single-dose oral Dex (0.6 mg/kg to a maximum of
      18 mg) or oral Pred (1 mg/kg per dose to a maximum of 30 mg) twice daily for 5
      days. After discharge, subjects were contacted by telephone at 48 h to assess
      symptoms and reevaluated in the ED in 5 days. The primary outcome was the number
      of days needed for Patient Self Assessment Score to return to baseline (score of
      0-0.5). MAIN RESULTS: Baseline characteristics of the 2 groups were similar. The
      mean number of days needed for Patient Self Assessment Score to return to
      baseline (0-0.5) in the Dex and Pred groups were 5.21 versus 5.22 days,
      respectively (mean difference, -0.01; confidence interval, -0.70, 0.68).
      Pulmonary index scores were similar in both groups at initial presentation,
      initial ED discharge and at the day 5 follow-up visit. At the first visit, mean
      time to discharge was 3.5 h (+/-1.93)for Dex and 4.3 h (+/-3.67) for Pred (mean
      difference, -0.8; confidence interval, -1.8, 0.2). Initial admission rate was 9%
      (Dex) versus 13.4% (Pred). There was no significant difference in the number of
      salbutamol therapies needed in the ED nor at home after discharge. For subjects
      discharged home, the admission rate after initial discharge was 4.9% (Dex) versus
      1.8% (Pred), resulting in overall hospital admission rates of 13.4% (Dex) and
      14.9% (Pred). CONCLUSION: A single dose of oral Dex (0.6 mg/kg) is no worse than
      5 days of twice-daily prednisolone (1 mg/kg per dose) in the management of
      children with mild to moderate asthma.

PMID- 17198211
TI  - Suspected child abuse among victims of home accidents being admitted to the
      emergency department: a prospective survey from Turkey.
AB  - OBJECTIVES: Association between home injuries and child abuse has received
      interest in Western countries. Inasmuch as it is now known that cultural
      differences may have an impact on child-rearing practices and the definition of
      maltreatment, we aimed to assess the suspected physical abuse in children
      presenting to the emergency department with home injuries and determine the risk
      factors associated with suspected child maltreatment in our region. METHOD: The
      study is prospective in design. The sample was composed of 87 children younger
      than 72 months with presenting histories of home accidents. Data were collected
      by interview with the parents and by application of various questionnaires and
      inventories to both children and their parents. RESULTS: Suspected physical abuse
      was identified in 16.1% of cases presenting with home injuries. The significant
      factors associated with suspected abuse were child's age younger than 12 months,
      having developmental delays in the social and self-care domains, younger paternal
      age, paternal alcohol abuse, marital discordancy, repeated history of home
      injuries, and requirement for radiological examination. CONCLUSION: A missed
      diagnosis of child abuse can result in repeated injury, cause severe morbidity,
      and even result in death. This research indicates the features of "victims of
      accidents" who require special attention to recognize suspected abuse at the
      emergency department. Cultural factors might also provide additional indications
      that might aid in determining the cases of child maltreatment.

PMID- 17198212
TI  - Perichondritis--a complication of high ear piercing.
AB  - Body piercing has become a fashionable trend in western culture. High ear
      piercing is common among the adolescent population and complications from this
      procedure although uncommon can be permanently disfiguring. We describe a case of
      perichondritis after high ear piercing in an adolescent male. A review of the
      history of body piercing, complications, risk factors, and treatment is
      presented.

PMID- 17198213
TI  - Referred shoulder pain preceding abdominal pain in a teenage girl with gastric
      perforation.
AB  - Referred shoulder pain is an important yet potentially distracting sign of
      serious intra-abdominal illness. A case is presented wherein shoulder pain
      preceded by several hours the onset of abdominal pain in a teenage girl with
      gastric perforation. The range of causes of gastric perforation and the
      pathophysiology of referred shoulder pain are discussed.

PMID- 17198214
TI  - Fatal polyarteritis nodosa with gastrointestinal involvement in a child.
AB  - Polyarteritis nodosa (PAN) is a necrotizing angiitis that predominantly affects
      small- and medium-sized arteries. Polyarteritis nodosa occurs rarely during
      childhood. Boys and girls seem to be equally affected, with a peak at the age of
      10 years. Rarely, severe and fatal gastrointestinal involvement is seen in PAN.
      Here, we report a 15-year-old boy with PAN, who had gastrointestinal involvement
      with multiple aneurysms of the hepatic and superior mesenteric arteries. This
      involvement could be demonstrated with conventional angiography and
      gastrointestinal bleeding scintigraphy. The progression of the symptoms and the
      decrease in the size of the aneurysms were noted after combination treatment with
      cyclophosphamide and prednisolone, but there was severe bleeding from small
      bowel, and it was taken under control by resection of jejunum. However, the
      patient died because of sepsis. In conclusion, severe gastrointestinal
      involvement in PAN is usually fatal despite aggressive therapy, as is the case in
      our patient.

PMID- 17198215
TI  - Bathing suit mesh entrapment: an unusual case of penile injury.
AB  - Penile injury is a rare chief complaint in the pediatric emergency department.
      The most common penile injuries are iatrogenic or postsurgical complications,
      blunt trauma, tourniquet injuries, fractures, and zipper injuries. We report a
      series of 3 cases of penile foreskin entrapment within the mesh lining of bathing
      suits as a new, recognized form of penile injury.

PMID- 17198216
TI  - Review of bispectral index monitoring in the emergency department and pediatric
      intensive care unit.
AB  - OBJECTIVES: Sedation is a key component in the management of pediatric patients
      both in the pediatric emergency department (PED) and pediatric intensive care
      unit (PICU) for the treatment of pain and anxiety. Bispectral (BIS) index
      monitoring has been developed to help clinicians assess degree of hypnosis with
      anesthesia and may be useful in these environments. METHODS: Literature searches
      were conducted through MEDLINE for case series/reports, retrospective studies,
      and randomized trials that evaluate the validity and applications of BIS
      monitoring in the PED and PICU. RESULTS: Most of the studies are case series or
      retrospective studies in children. There are several prospective studies
      assessing validation of the monitor in children. Only a few studies have been
      performed that assess the influence of monitoring on outcomes in these
      environments. CONCLUSIONS: Bispectral values correlate fairly well with commonly
      used clinical sedation scores, but more variability in the scores has been
      observed at lighter levels of sedation. More studies are needed to assess the
      value of titrating sedation in the PED and PICU within specific BIS parameters to
      reduce morbidity and costs associated with over-sedation.

PMID- 17198218
TI  - ECGs in the ED.

PMID- 17198219
TI  - A poisoning of topical importance.

PMID- 17198221
TI  - Central nervous system tumor: advance imaging and multispecialty approach.

PMID- 17198223
TI  - CNS tumors: monitoring therapeutic response and outcome prediction.
AB  - Brain tumors are a heterogeneous group of neoplasm with a diverse histological,
      molecular, and genetic spectrum and a widely variable clinical course and
      prognosis. Although most brain tumors, especially the malignant variety, remain
      difficult to cure, there are promising novel therapies and drug delivery systems
      that are under active investigation. One of the greatest challenges in developing
      effective therapy for brain tumors is the lack of specific markers to directly
      and accurately assess antitumor effect early and noninvasively. Further challenge
      lies in the fact that early treatment response can be transient and may not
      necessarily translate into long-term response or a favorable clinical outcome. In
      addition, there may be a small window of opportunity to assess therapeutic
      efficacy so that ineffective toxic therapy can be switched over to more effective
      therapy before there is widespread damage to the normal brain. The search for
      reliable and accurate predictors of treatment outcome that can be used to guide
      therapy and to improve survival in patients in malignant brain tumor has
      continued over several decades with modest success. This article will provide a
      general overview and current status of using quantitative maps derived from
      physiology-based magnetic resonance imaging to assess therapy response and to
      predict clinical outcome early during the course of therapy.

PMID- 17198224
TI  - Imaging for spine tumors and new applications.
AB  - OBJECTIVES: Discuss intramedullary, intradural/extramedullary, and extradural
      spinal tumors including imaging characteristics with emphasis on MR and advances
      in treatment. METHODS: Literature and institutional review. RESULTS: Spinal
      tumors: intramedullary, intradural/extramedullary, and extradural, comprise a
      wide range of histological tumors with an even wider range of clinical symptoms
      and prognostic features. They are relatively rare and if left untreated, can
      cause serious neurological deficits and disability. An accurate diagnosis is
      therefore crucial in determining prognosis and directing therapy. Magnetic
      resonance imaging (MRI) has revolutionized the diagnosis of intraspinal tumors,
      allowing for early detection and improved anatomical localization. Magnetic
      resonance has also become an integral part in staging of both primary and
      metastatic neoplasms of the spine for guiding therapy and is an excellent
      modality for follow-up. Advances in MRI (perfusion and molecular imaging) may
      help refine and describe these neoplasms for accurate treatment and prognosis in
      the future. Surveillance protocols and role of magnetic resonance are not well
      established. CONCLUSIONS: Magnetic resonance plays an integral role in evaluation
      of spinal tumors with increasing role in staging and treatment.

PMID- 17198222
TI  - Clinical magnetic resonance imaging of brain tumors at ultrahigh field: a state
      of-the-art review.
AB  - With the advancement of the magnetic resonance (MR) technology, the whole-body
      ultrahigh field MR system operated from 7 to 9.4 T becomes feasible for the
      routine patient imaging in clinical settings. The associated potentials and
      challenges from the perspectives of technology, physics, and biology as well as
      clinical application of the ultrahigh field MR systems are different from those
      systems operated at 3 T, 1.5 T, or lower field strength. In this article, we will
      present our initial experiences of brain tumor imaging using the 7 and 8 T whole
      body MR systems at the Ohio State University Medical Center and provide a brief
      overview pertinent to the ultrahigh field clinical MR systems.

PMID- 17198225
TI  - Contrast-enhanced magnetic resonance imaging of central nervous system tumors:
      agents, mechanisms, and applications.
AB  - Brain tumors are one of the most common neoplasms in young adults and are
      associated with a high mortality and disability rate. Magnetic resonance imaging
      (MRI) is widely accepted to be the most sensitive imaging modality in the
      assessment of cerebral neoplasms. Because the detection, characterization, and
      exact delineation of brain tumors require a high lesion contrast that depends on
      the signal of the lesion in relation to the surrounding tissue, contrast media is
      given routinely. Anatomical and functional, contrast agent-based MRI techniques
      allow for a better differential diagnosis, grading, and especially therapy
      decision, planing, and follow-up. In this article, the basics of contrast
      enhancement of brain tumors will be reviewed. The underlying pathology of a
      disrupted blood-brain barrier and drug influences will be discussed. An overview
      of the currently available contrast media and the influences of dosage, field
      strength, and application on the tumor tissue contrast will be given.
      Challenging, contrast-enhanced, functional imaging techniques, such as perfusion
      MRI and dynamic contrast-enhanced MRI, are presented both from the technical side
      and the clinical experience in the assessment of brain tumors. The advantages
      over conventional, anatomical MRI techniques will be discussed as well as
      possible pitfalls and drawbacks.

PMID- 17198226
TI  - Blood-brain barrier imaging and therapeutic potentials.
AB  - Much work has been done in the last several decades to improve the understanding
      of the molecular composition of the blood-brain barrier (BBB). Advances in
      magnetic resonance imaging have resulted in development of dynamic magnetic
      resonance imaging techniques to quantify permeability measurements across the
      brain endothelium. This review describes the basic anatomical and biochemical
      concepts of a BBB and the various techniques for magnetic resonance measurement
      of BBB permeability. To date, BBB permeability data have been shown to be useful
      in preoperative brain tumor grading and potentially also in determining the
      effectiveness of selective types of therapy. Explorative studies are evaluating
      new strategies for safe and effective altering of the BBB permeability to improve
      local drug delivery into brain tumors. As new antiangiogenesis drugs become
      available, BBB permeability imaging may also become critical as a surrogate
      angiogenesis marker to monitor tumor response to these agents. Finally, BBB
      permeability data may also prove useful in future applications to guide therapy
      in other nontumoral disease processes such as acute cerebral ischemia and
      inflammatory processes such as multiple sclerosis.

PMID- 17198227
TI  - Tumor imaging: radiation oncology perspective.

PMID- 17198228
TI  - Brain tumor imaging and surgical management: the neurosurgeon's perspective.
AB  - Advances in imaging technologies have influenced neurosurgical techniques and
      decisions and have enabled previously impossible resections, and neurosurgeons
      rely on the various modalities to make surgery as safe as possible. We look at
      the different technologies that have developed and how they are used by
      neurosurgeons, in combination with the knowledge of anatomy, to evaluate brain
      and spinal tumors and make surgical decisions that improve treatment outcomes.

PMID- 17198229
TI  - Brain tumor imaging and cancer management: the neuro-oncologists perspective.
AB  - Brain tumors remain a significant cause of morbidity and mortality and are often
      refractory to treatment. Neuroimaging, in particular magnetic resonance imaging
      (MRI) and associated techniques, has become an important tool for the neuro
      oncologist in the management of brain tumors. Magnetic resonance imaging is the
      most sensitive method to demonstrate the presence of a mass in the brain and can
      often narrow the differential diagnosis with nonneoplastic lesions such as
      cerebral abscess and subacute infarction. Once the diagnosis has been confirmed,
      MRI is essential for initial treatment planning, including surgical resection and
      radiation therapy. In selected patients, serial MRI will also be necessary to
      evaluate for response during adjuvant chemotherapy and to monitor for treatment
      induced toxicity. New magnetic resonance techniques such as magnetic resonance
      spectroscopy, diffusion-weighted imaging, and perfusion-based imaging methods
      will also be discussed where applicable.

PMID- 17198230
TI  - Proceedings of the 2006 World Transplant Congress, Boston, Massachusetts, USA.

PMID- 17198232
TI  - A transplant recipient's experience.

PMID- 17198231
TI  - Nobel prizes in medicine in the field of transplantation.

PMID- 17198233
TI  - Introduction of the president of the transplantation society, Kathryn Wood.

PMID- 17198234
TI  - The transplantation society: Building on success.

PMID- 17198235
TI  - The Transplantation Society Medawar Prize Ceremony 2006: Introduction.

PMID- 17198236
TI  - Introduction of Carl Gustav Groth.

PMID- 17198237
TI  - Medawar prize acceptance speech.

PMID- 17198238
TI  - Introduction of Pekka Hayry.

PMID- 17198239
TI  - Medawar prize acceptance speech.

PMID- 17198240
TI  - Introduction of Sir Peter John Morris.

PMID- 17198241
TI  - Medawar prize acceptance speech.

PMID- 17198242
TI  - Elevated soluble CD30 correlates with development of bronchiolitis obliterans
      syndrome following lung transplantation.
AB  - BACKGROUND: The long-term function of lung transplants is limited by chronic
      rejection (bronchiolitis obliterans syndrome, BOS). Due to lack of specific
      markers, BOS is diagnosed clinically. Because there is strong evidence that
      alloimmunity plays a significant role in the pathogenesis of BOS, we investigated
      whether soluble CD30 (sCD30), a T-cell activation marker, would correlate with
      BOS. METHODS: Sera collected serially from BOS+ (n = 20) and matched BOS- (n =
      20) lung transplant (LT) patients were analyzed for sCD30 by enzyme-linked
      immunosorbent assay. Pretransplant sera and sera from normal donors were also
      analyzed. RESULTS: PreLT levels were comparable to normal subjects. However,
      posttransplant there was a significant elevation in sCD30 levels during BOS
      development in all BOS+ patients, compared to BOS- (mean 139.8+/-10.7 vs. 14.8+/
      2.7 U/ml, P < 0.001). sCD30 levels declined in the BOS+ patients but were still
      elevated compared to BOS- (48.52+/-5.04 vs. 7.19+/-2.9, P < 0.0001). CONCLUSIONS:
      We conclude that sCD30 may represent a novel marker to monitor the development of
      BOS.

PMID- 17198243
TI  - Pretransplant soluble CD30 level has limited effect on acute rejection, but
      affects graft function in living donor kidney transplantation.
AB  - BACKGROUND: Serum soluble CD30 (sCD30) levels might be a useful marker of
      immunologic status in pre transplant (Tx) recipients. We retrospectively
      correlated preTx sCD30 levels (high versus low) on postTx graft survival,
      incidence of acute rejection, and graft function using stored preTx serum.
      METHODS: Of 254 recipients who underwent kidney Tx, 120 recipients were enrolled
      under the uniform criteria (living donor, age >25 years, viral hepatitis free,
      diabetes free). RESULTS: The preTx sCD30 was not significantly associated with
      differences in graft survival rate during 47.5+/-11.4 months of follow-up (P =
      0.5901). High sCD30 (> or =115 U/ml) was associated with a higher incidence of
      clinically or pathologically defined acute rejection than low sCD30, but the
      difference was not statistically significant (33.9% vs. 22.4%, P = 0.164). The
      response rate to antirejection therapy in patients with high sCD30 was inferior
      to those with low sCD30, but also was not statistically significant (33.3% vs.
      7.7%, P = 0.087). However, mean serum creatinine levels in high sCD30 patients at
      one month, one year, and three years postTx were significantly different from
      those with low sCD30 (P < 0.05). In multiple regression analysis, acute rejection
      episodes, donor age, kidney weight/recipient body weight ratio, and preTx sCD30
      levels were independent variables affecting the serum creatinine level three
      years postTx. CONCLUSION: PreTx sCD30 level has a limited effect on the incidence
      of acute rejection and response to antirejection treatment, but inversely and
      independently affects serum creatinine level after living donor kidney
      transplantation.

PMID- 17198244
TI  - Pretransplant soluble CD30 is a better predictor of posttransplant development of
      donor-specific antibodies and acute vascular rejection than panel reactive
      antibodies.
AB  - BACKGROUND: This study tests a hypothesis that pretransplant concentration of
      soluble CD30 (sCD30) is a better predictor of posttransplant development of donor
      specific HLA antibodies (DSA) and acute vascular rejection (AVR) than panel
      reactive HLA antibodies (PRA). METHODS: Pretransplant sera from 115 patients were
      evaluated for their PRA and sCD30 concentrations. All patients received
      calcineurin-inhibitor based immunosuppressive therapy. Objective measurements for
      rejection were biopsy-proven AVR episodes within first 6 months of the
      transplant. Posttransplant sera of patients with or without AVR were tested for
      the presence of DSA. RESULTS: AVR rate was 16% (18/115). Patients positive for
      PRA and sCD30 tests were at significantly higher risk for AVR compared to those
      patients negative for both tests (36% versus 5%, p = 0.01). Among negative PRA
      patients risk for AR was significantly elevated if they were also tested positive
      for sCD30 concentrations (21% versus 5%, p = 0.04). Of the 18 patients with AVR,
      14 were positive for sCD30, and 13 of them (93%) developed DSA posttransplant (p
      = 0.001) Nineteen patients without AVR were tested for DSA and sCD30
      concentrations. Only two of these 19 patients were positive for sCD30 and DSA.
      AVR was strongly associated with the patients tested positive for both the tests:
      DSA and sCD30 (p = 0.00007). Furthermore, patients with AVR are more likely to
      produce DSA than those without AVR (p = 0.02). CONCLUSION: These data support our
      hypothesis that patients positive for sCD30 contents are at high risk the
      development of DSA and AVR posttransplant regardless of their pretransplant PRA.

PMID- 17198245
TI  - Clinicopathologic monitoring of the skin and oral mucosa of the first human face
      allograft: Report on the first eight months.
AB  - BACKGROUND: The first human face allograft was performed in France on November
      27, 2005. We report herein the clinicopathologic findings from the skin and oral
      mucosa of this allograft during the first eight months. METHODS: Sequential
      biopsies were taken from the facial skin (n = 3), oral mucosa (n = 20), and
      sentinel skin graft (n = 11) from day 3 to day 220 postgraft and examined
      (immuno)histologically, using a pathological score previously proposed for
      evaluation of rejection in composite tissue (hand) transplantation. RESULTS: The
      patient developed clinically rejection episodes at day 20 and during the eighth
      month postgraft, manifesting with redness and edema of the facial skin, oral
      mucosa, and sentinel graft skin. Pathologically, changes suggestive of rejection
      grades 0, I, II, and III were seen in 1, 1, 1, and 0 biopsies of facial skin, 7,
      2, 1, and 1 biopsies of sentinel skin graft and 3, 5, 8, and 4 biopsies of oral
      mucosa, respectively. Pathological changes were generally more severe in the oral
      mucosa than in facial and sentinel graft skin (mean scores 1.85, 0.64, and 1,
      respectively). CONCLUSIONS: As it happens with other composite tissue allografts,
      close clinicopathologic monitoring of the skin (and oral mucosa) seems to be the
      most reliable way to detect rejection in the setting of human facial tissue
      allotransplantation. Apart from these rejection episodes, the skin and mucosa
      maintained a normal microscopic structure, paralleling functional recovery.

PMID- 17198246
TI  - A highly efficient living donor kidney exchange program for both blood type and
      crossmatch incompatible donor-recipient combinations.
AB  - BACKGROUND: Lack of deceased donors for kidney transplant patients in the
      Netherlands encouraged alternative options to expand the living donor pool for
      recipients who have a willing donor but cannot donate directly because of a
      positive crossmatch or ABO blood type incompatibility. A national donor kidney
      exchange was considered as a possible solution. METHODS: From January 2004 until
      June 2006, 146 couples from seven kidney transplantation centers were enrolled
      and participated in 10 match procedures. The Dutch Transplant Foundation was
      responsible for the allocation and the National Reference Laboratory for
      Histocompatibility in Leiden performed all the serological crossmatches. RESULTS:
      For 72 out of the 146 (49%) donor-recipient combinations, a match was found. The
      success rate in the positive crossmatch group was significantly (P = 0.0015)
      higher than in the ABO-incompatible group (44/69 vs. 28/77); median panel
      reactive antibodies of the matched recipients in the positive crossmatch group
      was 38% (0-100) and in the ABO-incompatible group 0% (0-27; P < 0.001). We were
      least successful for ABO blood type incompatible pairs with blood type O
      recipients, but for 9/53 (17%) there were possibilities. These nine blood type
      incompatible pairs were coupled to nine positive crossmatch pairs, which reflects
      the efficiency of combining the two categories of donor-recipient combinations
      into one program. CONCLUSION: The donor kidney exchange program in the
      Netherlands, in which all seven kidney transplantation centers participated,
      proved to be a successful program to expand the number of living donor kidney
      transplantations.

PMID- 17198248
TI  - Negative impact of new-onset diabetes mellitus on patient and graft survival
      after liver transplantation: Long-term follow up.
AB  - BACKGROUND: Little is known about the long-term consequences of new-onset
      diabetes mellitus (NODM) after liver transplantation (LTX). METHODS: In a chart
      review between 1996 and 2004, we evaluated its incidence and possible effect on
      patient and graft survival. Inclusion criteria were: adult primary LTX; deceased
      donor LTX without combined organs; and dual immunosuppression with tacrolimus and
      corticosteroid. Patients who died within six months after LTX were excluded. For
      analytical purposes, each patient was classified into one of four groups: 1)
      preLTX diabetes mellitus (DM): established DM before LTX; 2) sustained NODM: NODM
      sustained > or =6 months; 3) transitory NODM: NODM temporarily existed > or =1
      and <6 months; and 4) normal: no DM either pre- or postLTX. Patients who had NODM
      <1 month due to high-dose steroid (e.g., either immediate postLTX or rejection
      treatment) were considered as normal. Patient and graft survival was examined
      using Kaplan-Meier methodology. RESULTS: In all, 778 patients met the
      inclusion/exclusion criteria: preLTX DM 159 (20.4%), sustained NODM 284 (36.5%),
      transitory NODM 108 (13.9%), and normal 227 (29.2%). Median follow-up was 57.2
      months. There was a significant difference in patient (P = 0.012) and graft
      survival (P = 0.004) among the groups, with sustained NODM showing the poorest
      patient and graft survivals. Sustained NODM patients had a significantly higher
      rate of death due to infection, as well as graft failure due to chronic rejection
      and late onset hepatic artery thrombosis. CONCLUSION: NODM is a frequent
      complication with poor patient and graft survival after LTX.

PMID- 17198247
TI  - Alemtuzumab induction and tacrolimus monotherapy in pancreas transplantation: One
      and two-year outcomes.
AB  - BACKGROUND: Alemtuzumab (Campath-1H) induction with tacrolimus monotherapy has
      been shown to provide effective immunosuppression for kidney, liver, lung, and
      small bowel transplantation. This drug combination was evaluated in pancreas
      transplant recipients. METHODS: Sixty consecutive pancreas transplants (30
      simultaneous pancreas-kidney, 20 pancreas after kidney, and 10 pancreas alone)
      were carried out under this protocol between July 2003 to January 2005. The mean
      follow-up was 22 months (range 17-33). RESULTS: One-year patient, pancreas, and
      kidney allograft survival were 95%, 93%, and 90%, respectively. With 22 months
      follow-up, patient, pancreas, and kidney survival were 94%, 89%, and 87%,
      respectively. The rejection rate was 30% (18/60), with four patients (7%)
      experiencing steroid-resistant rejection. Major infection occurred in three (5%)
      patients resulting in two (3.3%) deaths from disseminated histoplasmosis and a
      herpes virus infection. One patient with cryptococcal meningitis was successfully
      treated. Seven (11.7%) patients experienced cytomegalovirus infection, all of
      whom responded to treatment with ganciclovir. One (1.7%) case of polymorphic
      posttransplant lymphoproliferative disease was seen, which regressed with a
      temporary discontinuation of tacrolimus and high-dose ganciclovir. The mean serum
      creatinine of the 30 simultaneous pancreas-kidney transplants at one year
      posttransplant was 1.37+/-0.33 mg/ml. The preexisting creatinine in pancreas
      after kidney transplants was not adversely affected by this immunosuppressive
      protocol. CONCLUSION: A single dose of perioperative alemtuzumab followed by
      daily tacrolimus monotherapy provides effective immunosuppression for pancreas
      transplantation, but the optimal use of this drug combination is not yet clear.

PMID- 17198249
TI  - Follow-up study of the first successful living donor islet transplantation.
AB  - BACKGROUND: Islet transplantation has become an option for the treatment of
      insulin-dependent diabetes mellitus and is usually performed using brain-dead
      heartbeating donors. However, we have very limited number of such donors in
      Japan; therefore, it is not allowed to perform islet transplantation with brain
      dead donors. In order to perform islet transplantation in Japan, we need to seek
      new donor resources. METHODS: We performed the first successful living-donor
      islet transplantation. In this case, the recipient had brittle diabetes with
      hypoglycemic unawareness. The donor was deemed qualified after undergoing both
      metabolic and preoperative assessments. Distal pancreatectomy was performed using
      open laparotomy and more than 400,000 islets were isolated and transplanted
      immediately. RESULTS: The recipient has been insulin independent posttransplant
      with positive C-peptide for more than one year. She no longer suffers from
      hypoglycemic unawareness and displayed a substantial improvement in hemoglobulin
      (Hb) A1C. The donor's clinical course was uneventful, which allowed her to return
      to her job within one month. She maintained normal fasting C-peptide and HbA1C
      levels during follow-up period. CONCLUSION: In our first case of living donor
      islet transplantation, both the donor and the recipient have been maintaining
      excellent glycemic control with no untreatable complications for more than one
      year.

PMID- 17198250
TI  - Long-term graft outcome with mycophenolate mofetil and azathioprine: A paired
      kidney analysis.
AB  - BACKGROUND: Randomized controlled trials and U.S. Registry data have demonstrated
      that mycophenolate mofetil (MMF) reduces acute rejection rates and improves graft
      survival. We undertook the first paired kidney analysis comparing the effects of
      MMF and azathioprine on graft outcome in the United Kingdom. METHODS: In all, 238
      deceased donors from 1999 to 2002 who donated one kidney to a patient treated
      with MMF and the other kidney to a patient treated with azathioprine were
      identified from the national transplant database held by U.K. Transplant. Graft
      function and rates of change of graft function were compared using multiple
      linear regression analyses adjusting for covariates on an intention-to-treat
      basis. Incidence of acute rejection and delayed graft function were studied using
      logistic regression. Patient and graft survival censored for death were evaluated
      with Cox regression analyses. RESULTS: The MMF-treated patients exhibited a
      nonsignificant trend towards improved graft function but with increased rejection
      rates (44% versus 31%, P < 0.01). Treatment with MMF did not reduce delayed graft
      function rates. Univariate analysis showed that graft survival was inferior in
      MMF-treated patients (90% versus 95%, log-rank, P = 0.02) but in multivariate Cox
      regression models, MMF treatment was not a significant factor. Surprisingly, in
      the first year 32% of patients achieved daily doses of less than 2 g of MMF
      compared to 18% of patients who received less than 100 mg of azathioprine (P <
      0.01). CONCLUSION: In this real-life study, there was no difference in patient or
      graft outcome between MMF and azathioprine treated groups despite increased
      rejection rates in patients receiving MMF therapy.

PMID- 17198251
TI  - Successful transplantation of kidneys from deceased donors with acute renal
      failure: Three-year results.
AB  - BACKGROUND: Kidneys from deceased donors with acute renal failure (ARF) are
      generally not accepted for transplantation because of the expected poor outcome.
      This prospective study examined the utilization of kidneys from donors with ARF
      for transplantation and the outcomes. METHODS: Fifty-five kidneys from donors
      with ARF were transplanted. The outcome was compared with concurrent and matched
      55 recipients of standard criteria donor (SCD) kidneys and 55 expanded criteria
      donor (ECD) kidneys. ARF kidneys were accepted from donors aged <50 years, a
      negative history for kidney disease, and a negative pretransplant biopsy for
      chronic structural changes. The immunosuppression was similar in all three
      groups. The outcome measurements included three-year patient and graft survival,
      biopsy-proven acute rejection (BPAR), subclinical acute rejection (SCAR), and
      chronic allograft nephropathy (CAN), serum creatinine, and creatinine clearance.
      RESULTS: Three-year patient and graft survival was 90% and 90% in ARF group, 100%
      and 89% in SCD group and 83% and 66% in ECD group. BPAR and SCAR were comparable
      in the groups but CAN was significantly higher in ECD group. Mean serum
      creatinine levels were 1.9+/-1.1, 1.9+/-0.9, and 2.2+/-1.3 mg/dl and mean
      creatinine clearances were 66+/-15, 68+/-14, and 58+/-10 mls/minute in ARF, SCD,
      and ECD groups, respectively (SCD and ARF vs. ECD P = 0.04). CONCLUSIONS:
      Transplantation of kidneys from selected deceased donors with ARF provides
      comparable survival and function compared to kidneys from non-ARF donors and may
      be considered for transplantation to expand the donor pool to overcome the
      current acute shortage of kidneys.

PMID- 17198252
TI  - Incidence of end-stage renal disease among live kidney donors.
AB  - BACKGROUND: The increasing use of living kidney donors requires knowledge about
      long-term effects, especially number and causes of donors with end-stage renal
      disease (ESRD). METHODS: A retrospective data analysis of 1,112 consecutive
      living kidney donors who underwent nephrectomy from 1965 until 2005 at
      Sahlgrenska University Hospital. Case reports were sought with help from
      nephrologists in the region and data from Swedish Registry of Active Uremic
      Treatment (SRAU). RESULTS: The number of cases with end stage kidney failure
      among living kidney donors was 6/1112, that is 0.5%. The donors had reached ESRD
      during the years 2001-2006, that means 36-41 years after start of the living
      donor program. The donors were 45-89 years old, median 77 years, and five of six
      were males. Time since donation was 14-27 years, median 20 years, for the donors
      developing ESRD. The diagnoses were nephrosclerosis (4 cases), postrenal failure
      (1 case), and renal carcinoma (1 case). The expected incidence for development of
      ESRD according to incidence in the general population would have been two donors
      but we found six. However, considering the high age of the donors in this follow
      up, the age-matched incidence is calculated to be closer to six donors due to
      higher incidence in the aged. CONCLUSION: In all 0.5% of the donors developed
      ESRD. Due to high age of the uremic donors, there seems to be no increased
      incidence.

PMID- 17198253
TI  - Pancreas transplantation under alemtuzumab (Campath-1H) and tacrolimus:
      Correlation between low T-cell responses and infection.
AB  - BACKGROUND: Alemtuzumab induction and tacrolimus-based immunosuppression has been
      effective in pancreas transplantation. Despite the encouraging results of this
      minimalistic approach to immunosuppression, infection still remains a significant
      cause of morbidity. The Cylex ImmuKnow [corrected] assay was used in this study
      to compare pancreas recipient clinical states (stable, rejection, infection) with
      T cell responses. METHODS: Blood samples were taken from pancreas recipients
      pretransplant and at approximately three-month intervals posttransplant for
      analysis of T cell responses. When possible, T cell responses were also
      quantified during changes in clinical status (infection or rejection). RESULTS: A
      range between 100-300 ng/ml adenosine triphosphate (ATP) was found in stable
      patients (mean 194+/-123, n = 51) with good graft function and no infection or
      rejection. A low T cell response was highly correlated with infectious states.
      The fourteen patients with infections/posttransplant lymphoproliferative disease
      had a mean ATP of 48 ng/ml. Risk hazard analysis showed that patients with ATP
      levels <100 ng/ml were four to seven times more susceptible to infection compared
      to stable patients. Four patients with rejection showed a T cell response of 550
      ng/ml ATP, which was statistically significant compared to stable patients,
      although the sampling numbers (9) were too small to be conclusive. CONCLUSION:
      The Cylex ImmuKnow [corrected] assay is a valuable tool to more precisely
      modulate immunosuppression in pancreas transplant patients. In particular, the
      assay is extremely useful in detecting overly immunosuppressed patients
      vulnerable to infections.

PMID- 17198255
TI  - Transplant tourism: Outcomes of United States residents who undergo kidney
      transplantation overseas.
AB  - BACKGROUND: Although international commerce in kidney transplantation is a
      reality, little is known about U.S. residents who travel abroad for kidney
      transplantation. METHODS: We retrospectively reviewed the clinical outcomes of
      patients who were evaluated at the University of Minnesota Medical Center or
      Hennepin County Medical Center, but then surreptitiously underwent kidney
      transplantation overseas. RESULTS: We identified 10 patients who underwent kidney
      transplantation outside the United States between September 16, 2002 and June 30,
      2006 and then returned for care in our programs. Eight were transplanted in
      Pakistan (all Somali), one was transplanted in China (Chinese), and one was
      transplanted in Iran (Iranian). All but one had a living donor. Mean age was
      36.8+/-12.5 years with median follow-up of 2.0 years (range 0.4-3.7). Three
      patients communicated their intent to travel abroad before transplantation.
      Induction immunosuppressive therapy (if any) was available in 3/10, and initial
      maintenance immunosuppression was known in 5/10. Complications were primarily
      infectious, with six potentially life-threatening infections in four patients. At
      last follow-up, mean serum creatinine was 1.13+/-0.34 mg/dL, acute rejection
      occurred in 2/10, 1/10 grafts failed due to acute rejection, and 9/10 patients
      were alive. CONCLUSIONS: Kidney function and graft survival were generally good
      after surreptitious overseas kidney transplantation. Major problems included
      incomplete perioperative information communicated to the posttransplant care
      facility and a high incidence of posttransplant infections. Longer follow-up and
      detailed cost analysis are needed to better understand the implications of the
      growing phenomenon of transplant tourism.

PMID- 17198254
TI  - Utilization of extended donor criteria liver allograft: Is the elevated risk of
      failure independent of the model for end-stage liver disease score of the
      recipient?
AB  - BACKGROUND: The goal of this analysis was to determine if outcomes from the use
      of extended criteria donor (ECD) livers were dependent upon the Model for End
      Stage Liver Disease (MELD) score of the recipient. METHODS: The Organ Procurement
      and Transplantation Network (OPTN) database as of March 4, 2006 was used for the
      analysis. Data from 12,056 adult liver transplant (LTx) recipients between June
      1, 2002 and June 30, 2005 was analyzed. The donor risk index (DRI) was calculated
      as previously reported. A DRI of > or =1.7 was classified as ECD. Relative risk
      (RR) estimates were derived from Cox regression models adjusted for DRI,
      recipient MELD, age, sex, ethnicity, diagnosis, and year of transplant. RESULTS:
      Data from 2,873 grafts falling in the ECD category (23.8%) and their recipients
      were analyzed. Recipients with low MELD scores (<15) received the highest
      proportion of ECD livers (33%). ECD livers were associated with a significant
      increase in the RR of graft failure within each MELD category. However, this
      effect held within each of the three MELD categories. CONCLUSION: The use of ECD
      grafts expands the organ pool at expense of increased RR of liver failure. Our
      analysis showed no significant interaction between DRI and MELD score of the
      recipient. The fact that there is no additional impact of ECD livers in
      recipients with high MELD scores suggests that this group of patients may benefit
      from this pool of grafts.

PMID- 17198256
TI  - The older living kidney donor: Part of the solution to the organ shortage.
AB  - BACKGROUND: Strategies to increase kidney transplantation are urgently needed.
      METHODS: We studied all (n = 73,073) first kidney-only transplant recipients in
      the United States between 1995 and 2003 to determine the incidence and outcomes
      of living donor transplantation as a function of donor age. Because 90% of living
      donors were <55 years, we defined older living donors as > or =55 years. Factors
      associated with transplantation from older living donors and the association of
      living donor age with allograft function and survival were determined. RESULTS:
      Recipients of older age, female gender, white race, and preemptive transplants
      had higher odds of older living donor transplantation. Older living donor
      transplantation was more likely from spousal donors rather than blood relatives,
      and more likely when a husband was the donor. The glomerular filtration rate
      (GFR) one year after transplantation decreased with increasing donor age (P <
      0.001). Graft survival from living donors > or =55 years was 85% and 76% at three
      and five years (compared to 89% and 82% with living donors <55 years, and 82% and
      73% with deceased donors <55 years). In a multivariate model, the risk of graft
      loss with living donors 55-64 years was similar to that with deceased donors <55
      years, while recipients from living donors 65-69 years (HR = 1.3, 95% CI: 1.1
      1.7) and >70 years (HR = 1.7, 95% CI: 1.1-2.6) had a higher relative risk of
      graft loss. CONCLUSIONS: Outcomes are excellent with living donors <65 years.
      Expanded use of older living donors may help meet the demand for transplantation.

PMID- 17198257
TI  - The use of oral glucose tolerance tests to risk stratify for new-onset diabetes
      after transplantation: An underdiagnosed phenomenon.
AB  - BACKGROUND: Fasting glucose measurements are insensitive at detecting new-onset
      diabetes after transplantation (NODAT) and ignore the diagnosis of impaired
      glucose tolerance (IGT). Both NODAT and IGT confer a higher risk of developing
      cardiovascular disease. IGT is also a risk factor for NODAT. The aim of this
      study was to use an oral glucose tolerance test (OGTT) to risk stratify for NODAT
      and IGT in renal transplant recipients and to relate cardiovascular and
      phenotypic risk with glycemic dysregulation. METHODS: In all, 858 renal
      transplant recipients are under follow up at the University Hospital of Wales,
      Cardiff, UK. Excluded patients had pretransplant diabetes (78), NODAT (89), or
      were transplanted less than six months (47), leaving 646 recipients. All
      remaining recipients with two fasting blood glucoses between 5.6 and 6.9 mmol/L
      were invited to have an OGTT. A diagnosis of NODAT, IGT, and impaired fasting
      glucose (IFG) was based on World Health Organization guidelines. RESULTS: We
      identified 134 patients who fulfilled the inclusion criteria, of whom 122 had an
      OGTT (91% of cohort). In all, 51% of patients were found to have abnormal glucose
      metabolism: 10% NODAT, 14% combined IGT/IFG, 9% IGT alone, and 18% IFG alone.
      Clinical phenotype was not predictive of diabetic risk on multivariate analysis.
      CONCLUSIONS: Our results confirm fasting glucose underestimates the prevalence of
      NODAT and ignores the prevalence of IGT. These findings suggest routine use of an
      OGTT in renal transplant recipients is a valuable clinical tool to risk stratify
      each patient for the development of NODAT and cardiovascular disease.

PMID- 17198258
TI  - Risk factors for development of new-onset diabetes mellitus after kidney
      transplantation.
AB  - BACKGROUND: New-onset diabetes mellitus after kidney transplantation (NODM) is an
      important co morbid condition that is associated with inferior graft and patient
      survival. The objective of this study was to identify donor, recipient and
      transplant factors, and choices of immunosuppression associated with development
      of NODM using Organ Procurement Transplant Network/United Network of Organ
      Sharing database (OPTN/UNOS). METHODS: From January 2004 to December 2005, 15,309
      adult kidney transplants alone with at least one follow-up report as of March
      2006 were identified in the OPTN/UNOS database. Among these, 1,581 patients
      developed NODM during the follow-up period. We examined the risk factors of NODM
      using multivariate Cox regression analysis using the time to diagnosis of NODM as
      a time-varying end point. Other events such as graft loss, patient death, and
      lost to follow-up were censored. RESULTS: NODM was reported in 10% in our study
      population with mean follow-up time of 306 days. After adjusting for other known
      factors, independent factors associated with the development of NODM included
      recipient age (29% increase of relative risk [RR] for every 10-year age
      increment), obesity (RR = 1.39 for body mass index [BMI] 25-30 and RR = 1.85 for
      BMI > 30 vs. BMI < 25), tacrolimus use (RR = 1.50), hepatitis C virus (HCV)
      positivity (RR = 1.42), and African-American recipients (RR = 1.32). Alemtuzumab
      was associated with a lower risk of NODM (RR = 0.52). DISCUSSION: Using OPTN/UNOS
      database, we identified risk factors for development of NODM. Some of these
      factors are potentially modifiable, including obesity, HCV infection, and the use
      of tacrolimus. Clinical trials are needed to assess whether modifying these
      "modifiable risk factors" will indeed prevent NODM.

PMID- 17198259
TI  - The MDR1/ABCB1 gene, a high-impact risk factor for cardiac transplant rejection.
AB  - BACKGROUND: Variations in the expression and activity levels of the multidrug
      resistance MDR1/ABCB1 encoded P- glycoprotein (P-gp) have an impact on the
      therapeutic efficacy of many drugs. C3435T and G2677 polymorphisms of the
      MDR1/ABCB1 gene correlate with cellular expression levels of P-gp, a membrane
      bound efflux pump which removes a multitude of drugs, including chemotherapy
      drugs and immunosuppressants, from cells. We aimed to investigate whether the
      phenomenon of drug resistance, mediated by the MDR1/ABCB1 gene and seen in tumor
      cells to chemotherapeutic agents, is important in the field of transplantation,
      predisposing some patients to resistance to immunosuppressants. METHODS: G2677
      and C3435T polymorphisms of the ABCB1 gene were determined by PCR in 170 heart
      transplant recipients. We examined the relationship between MDR1/ABCB1
      polymorphisms and endomyocardial biopsy-proven rejection (EBPR) determined by
      biopsy performed at set intervals according to a standard protocol. RESULTS: A
      significant relationship was found between a patient's C3435T genotype and
      freedom from first grade > or =3A rejection episode. 3435-CC recipients were 1.8
      times (1.05-3.09; P = 0.03) more likely to undergo a > or =3A rejection episode
      in the first 12 months. Haplotypes derived from the G2677 and C3435T
      polymorphisms (GG/CC, GT/CT and TT/TT) amplified this phenomenon further (log
      rank, P = 0.03; HR 2.18; 1.21-4.26; P = 0.02). CONCLUSIONS: ABCB1 polymorphisms
      correlate with freedom from grade > or =3A EBPR and we believe that this may be
      attributed to MDR1/ABCB1 encoded P-gp mediating the efflux of immunosuppressants
      out of leukocytes, with depleted immunosuppressant levels in leukocytes
      manifesting as increased cellular rejection.

PMID- 17198260
TI  - Factors affecting graft survival after liver transplantation from donation after
      cardiac death donors.
AB  - BACKGROUND: Liver transplantation from donation after cardiac death (DCD) donors
      is an increasingly common approach for expansion of the donor organ supply.
      However, transplantation with DCD livers results in inferior graft survival. In
      this study, we examined donor and recipient characteristics that are associated
      with poor allograft outcomes and present a set of criteria that permit allograft
      survival that is comparable to that of donation after brain death (DBD) grafts in
      both low- and high-risk recipients. METHODS: The United Network for Organ
      Sharing/Organ Procurement and Transplantation Network Liver Transplantation
      Registry between January 1996 and March 2006 was investigated. Adult DCD liver
      transplants (n = 874) were included. RESULTS: A DCD risk index was developed
      using the statistically significant factors from a multivariate Cox model:
      history of previous transplantation, life support status at transplantation,
      donor age, donor warm ischemia time (DWIT), and cold ischemia time (CIT).
      Favorable DCD donor criteria were donor age < or =45 years, DWIT < or =15 min,
      and CIT < or =10 hr. Four risk groups were developed based upon index scores that
      showed different graft survival. Graft survival of the favorable DCD group (84.9%
      at 1 year, 75.2% at 3 years, and 69.4% at 5 years) was comparable to that for DBD
      liver transplantation irrespective of recipient condition. Increasing donor age
      was more highly predictive of poor outcomes in DCD compared to DBD, especially in
      recipients in poor preoperative condition. CONCLUSIONS: DCD livers from young
      donors with short DWIT and CIT should be given greater consideration in order to
      expand the number of available donor organs.

PMID- 17198261
TI  - Randomized controlled trial of FTY720 versus MMF in de novo renal
      transplantation.
AB  - BACKGROUND: Phase II trials of FTY720, a novel immunomodulator, have shown
      promise in preventing rejection with both standard and reduced cyclosporine
      exposure. This study was designed to confirm those findings. METHODS: This one
      year, multicenter, randomized, phase III study in 696 de novo renal transplant
      patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5
      mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC.
      All patients received concomitant corticosteroid therapy without antibody
      induction. The primary efficacy composite endpoint was the incidence of first
      treated biopsy-proven acute rejection (treated BPAR), graft loss, death or
      premature study discontinuation at month 12. RESULTS: FTY720 2.5 mg plus FDC was
      demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint
      (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was
      discontinued due to an increased incidence of acute rejection episodes (primary
      endpoint 43.3%). FTY720 was associated with significantly lower creatinine
      clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and
      MMF plus FDC of 8 ml/min. CONCLUSIONS: While FTY720 2.5 mg plus FDC yielded
      similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50%
      reduction in cyclosporine exposure. The associated lower creatinine clearance
      indicated that FTY720 combined with cyclosporine provided no benefit over
      standard care.

PMID- 17198263
TI  - Predictors of disease recurrence following neoadjuvant chemoradiotherapy and
      liver transplantation for unresectable perihilar cholangiocarcinoma.
AB  - BACKGROUND: Sixty-five patients with unresectable hilar cholangiocarcinoma (CCA)
      have undergone orthotopic liver transplantation (OLT) after neoadjuvant
      chemoradiotherapy per a clinical care protocol developed in 1993. We reviewed our
      experience with the aim to identify clinicopathological predictors of disease
      recurrence. METHODS: All patients with CCA that underwent OLT at our institution
      between 1993 and January 1, 2006 were treated in accord with our published
      protocol. We analyzed multiple clinical and explant pathologic factors using Cox
      regression analysis. RESULTS: Sixty-five patients with CCA underwent OLT. Four
      patients died within six months due to postoperative complications. At last
      follow-up, 11 patients (17%) had developed recurrence seven to 64 months after
      OLT. Mean time to recurrence was 29 months, and eight patients had died from
      recurrent disease. Patient and disease-free survival were 76% and 60% five years
      after OLT. Predictors of recurrence were older age, pretransplant cancer antigen
      (CA) 19-9 >100 U/ml, prior cholecystectomy, mass on cross-sectional imaging,
      residual tumor in explant >2 cm, tumor grade and perineural invasion in explant.
      Underlying primary sclerosing cholangitis, percutaneous biliary intubation,
      gender, and other time points for CA 19-9 were not associated with recurrence.
      Prolonged staging-to-OLT intervals for patients transplanted after implementation
      of model for end-stage liver disease (MELD) showed a trend toward increased
      recurrence. CONCLUSIONS: Older patients and those with high CA-19.9 levels, and
      larger tumors are more likely to develop recurrent disease. Prolonged waiting
      time may emerge as a significant risk factor with longer follow-up. These
      findings may guide patient selection, applicability of live donor transplantation
      and MELD score exceptions for this aggressive protocol.

PMID- 17198262
TI  - Pregnancy outcomes in solid organ transplant recipients with exposure to
      mycophenolate mofetil or sirolimus.
AB  - BACKGROUND: Animal and limited human studies have raised concerns as to the
      safety of in utero exposure to mycophenolate mofetil (MMF) and sirolimus (SRL) in
      transplant recipients. This study examined the outcomes of pregnancies with
      exposure to MMF or SRL from 30 female transplant recipients (39 pregnancies) who
      have reported pregnancies to the National Transplantation Pregnancy Registry.
      METHODS: Data were collected via questionnaires, phone interviews and medical
      records. RESULTS: There were 18 kidney recipients reporting 26 pregnancies with
      exposure to MMF: 15 livebirths (LB), 11 spontaneous abortions (SA). Structural
      malformations were reported in four of the 15 children (26.7%) including:
      hypoplastic nails and shortened fifth fingers (one), microtia with cleft lip and
      palate (one), microtia alone (one), and neonatal death with multiple
      malformations (one). One kidney/pancreas (K/P) recipient reported one SA. Three
      liver recipients reported three pregnancies; two LB (no malformations), and one
      second trimester SA. Two heart recipients reported one LB (no malformations) and
      two SA. SRL exposures included seven recipients (four kidney, one K/P and two
      liver) reporting four LB (one infant whose mother was switched from MMF to SRL
      during late pregnancy had cleft lip and palate and microtia) and three SA.
      CONCLUSIONS: A higher incidence of structural malformations was seen with MMF
      exposures during pregnancy compared to the overall kidney transplant recipient
      offspring, while no structural defects have as yet been reported with early
      pregnancy sirolimus exposures. Centers are encouraged to report all pregnancy
      exposures in transplant recipients.

PMID- 17198264
TI  - Pediatric liver and kidney transplantation with allografts from DCD donors: A
      review of UNOS data.
AB  - INTRODUCTION: Donation after cardiac death (DCD) is recognized as an important
      source of allografts to bridge the growing disequilibrium between the number of
      donors and recipients. Current transplant experience with DCD organs has focused
      on the adult recipient population, however little is known about the pediatric
      recipient experience. While there is increasing acceptance of these grafts in
      adults, transplant centers appear reluctant to use these grafts in the pediatric
      population. METHODS: We reviewed the United Network for Organ Sharing database
      from 1995-2005 to determine the national experience with pediatric recipients of
      DCD organs. RESULTS: Among 4026 renal transplants performed in children 18 years
      and younger, 26 (0.6%) received a renal allograft from a DCD donor. Ten (38.5%)
      received kidney allografts from pediatric donors (age < or = 18) and 16 (61.5%)
      from adult donors (age > 18 years). Graft survival at one and five years was
      82.5%, 74.3% for kidneys from DCD donors compared to 89.6%, 64.8% from brain dead
      donors (DBD) (P = 0.7). Among 4991 liver transplants, 19 (0.4%) were from DCD
      donors. Sixteen patients (84.2%) received livers from pediatric donors and three
      (15.8%) from adult donors. Graft survival at one and five years was 89.2%, 79.3%
      for livers from DCD, compared to 75.6%, 65.8% for DBD (P = 0.3). CONCLUSION: The
      use of DCD donors in the pediatric population is very limited; however graft
      survival is comparable to DBD grafts. Although pediatric centers may have been
      reluctant to utilize this donor source, this limited experience demonstrates that
      the select use of DCD organs can produce acceptable and durable graft survival in
      the pediatric population.

PMID- 17198265
TI  - Adoptive transfer of TRAIL-expressing natural killer cells prevents recurrence of
      hepatocellular carcinoma after partial hepatectomy.
AB  - BACKGROUND: Antitumor activity of the liver natural killer (NK) cells reportedly
      decreases after partial hepatectomy, suggesting that patients with such depressed
      immune status are susceptible to the recurrence of hepatocellular carcinoma
      (HCC). We hypothesize that adoptive immunotherapy using activated NK cells can be
      a novel strategy to improve the depressed immune status in patients with HCC
      after hepatectomy or partial liver transplantation. In the present study, we have
      tested this hypothesis by using a mouse model. METHODS: Intraportal injection of
      1-5 x 10(6) Hepa1-6 cells (hepatoma cell line) did not result in liver metastases
      in untreated B6 mice, but led to the growth of liver metastases after extensive
      partial hepatectomy. Utilizing this murine HCC metastasis model, we investigated
      the antitumor activity of both remnant liver and exogenously transferred NK
      cells. RESULTS: The anti-HCC activity of liver NK cells significantly decreased
      after partial hepatectomy. The expression of CD69 and tumor necrosis factor (TNF)
      related apoptosis-inducing ligand (TRAIL) on liver NK cells was temporarily
      downregulated. The adoptive transfer of NK cells, including a TRAIL-expressing
      fraction, extracted from the liver perfusates of poly I:C-stimulated B6 mice
      inhibited the growth of liver metastasis in B6 or (B6xBALB/c) F1 (B6CF1) mice
      that underwent hepatectomy and received intraportal Hepa1-6 injection.
      CONCLUSIONS: These findings indicate that adoptive immunotherapy using activated
      NK cells extracted from normal liver perfusates may be a novel technique for
      reconstituting the depressed immune status in cases of living donor liver
      transplantation involving HCC patients, recipients of a partial liver graft.

PMID- 17198266
TI  - Control of allograft rejection by applying a novel nuclear factor-kappaB
      inhibitor, dehydroxymethylepoxyquinomicin.
AB  - BACKGROUND: Nuclear factor (NF)-kappaB plays a crucial role in lymphocyte
      activation, proliferation, and survival. We examined the immunosuppressive effect
      of a newly developed NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ)
      in allotransplantation. METHODS: Purified C57BL/6 (H-2b) T cells were used for in
      vitro studies examining activation, proliferation, cytokine production and
      nuclear NF-kappaB and nuclear factor of activated T cells (NFAT) protein levels.
      A fully major histocompatibility complex incompatible BALB/c (H-2d)-to-C57BL/6
      mice cardiac transplantation model was utilized for in vivo studies. DHMEQ was
      given intraperitoneally to transplant recipients at a various dose starting from
      day 0. In some, DHMEQ was administered concomitantly with tacrolimus. RESULTS:
      DHMEQ significantly suppressed alphaCD3 + alphaCD28 monoclonal antibody-triggered
      T-cell proliferation, CD25/CD69 expressions, and both interleukin-2 and
      interferon (IFN)-gamma production in a dose-dependent fashion. DHMEQ blocked
      nuclear translocation of NF-kappaB but not NFAT in activated T cells. Combined
      treatment with DHMEQ and tacrolimus significantly suppressed T cell activation as
      compared to that of mono-therapy with either agent alone. Single DHMEQ treatment
      moderately prolonged cardiac allograft survival. Further, combination of DHMEQ
      plus tacrolimus markedly prolonged graft mean survival time (MST) to 59.5 days
      when compared to either DHMEQ (MST: 10 days) or tacrolimus (MST: 13 days)
      treatment alone. Such effect was associated with inhibition of mixed lymphocyte
      reaction against donor antigen, IFN-gamma producing splenocytes and graft
      cellular infiltration as examined at 5 and 12 days posttransplantation.
      CONCLUSION: DHMEQ inhibits nuclear translocation of NF-kappaB but not NFAT in
      activated T cells, and prolongs allograft survival. Blocking both NF-kappaB and
      NFAT by DHMEQ and tacrolimus induces potent immunosuppression, which may become a
      new modality in controlling allograft rejection.

PMID- 17198267
TI  - Prevention of renal ischemic injury by silencing the expression of renal caspase
      3 and caspase 8.
AB  - BACKGROUND: Apoptotic pathways mediated by caspases play a critical role in renal
      ischemia-reperfusion injury (IRI). Downregulation of the caspase cascade, using
      small interfering RNA (siRNA) to silence the expression of caspase 3 and caspase
      8, may have substantial therapeutic potential for limiting renal injury. METHODS:
      IRI was induced in mice by clamping of the renal vein and artery for 25 or 35 min
      at 37 degrees C. Caspase 3 and caspase 8 (caspase 3/8) siRNA was administrated by
      hydrodynamic injection. Quantitative polymerase chain reaction (PCR) and
      immunohistochemistry were used to analyze the gene silencing efficacy, and the
      therapeutic effects of siRNA were evaluated by renal function analysis,
      histological examination, and overall survival of mice suffering from IRI.
      RESULTS: In this study, we have shown, using quantitative PCR, that IRI is
      associated with increased levels of renal caspase 3/8 mRNA. Mice treated with
      caspase 3/8 siRNA showed a significant down-regulation in kidney expression of
      caspase 3/8 at both, transcriptional and protein levels. Kidney function in IRI
      was protected by siRNA therapy, as levels of blood urea nitrogen and creatinine
      were significantly reduced in mice treated with siRNA. Histological examination
      demonstrated that tissue injury caused by IRI was significantly reduced as a
      result of caspase 3/8 siRNA treatment. Furthermore, survival data showed that
      more than 70% of mice in siRNA-treated groups survived until the end of the eight
      day observation period. CONCLUSION: Herein, we have demonstrated the therapeutic
      potential of using siRNA to knock down the expression of caspases and prevent
      acute renal injury.

PMID- 17198268
TI  - Gene transfer of programmed death ligand-1.Ig prolongs cardiac allograft
      survival.
AB  - BACKGROUND: The CD28 homologue programmed death-1 (PD-1) and its ligands, PD-L1
      and PD-L2 (which are homologous to B7), constitute an inhibitory pathway of T
      cell costimulation. The PD-1 pathway is of interest for immune-mediated diseases
      given that PD-1-deficient mice develop autoimmune diseases. We have evaluated the
      effect of local overexpression of a PD-L1.Ig fusion protein on cardiac allograft
      survival. METHODS: Adenovirus-mediated PD-L1.Ig gene transfer was performed in
      F344 rat donor hearts placed in the abdominal position in Lewis recipients.
      Inflammatory cell infiltrates in the grafts were assessed by
      immunohistochemistry. RESULTS: Allografts transduced with the PD-L1.Ig gene
      survived for longer periods of time compared with those receiving noncoding
      adenovirus or virus dilution buffer alone: median survival time (MST), 17 (range:
      16-20) days vs. 11 (8-14) and 9 (8-13) days, respectively (P < 0.001). PD-L1.Ig
      gene transfer combined with a subtherapeutic regimen of cyclosporin A (CsA) was
      superior to CsA alone: MST, 25 (15-42) vs. 15 (13-19) days (P < 0.05). PD-L1.Ig
      gene transfer was associated with decreased numbers of CD4 cells and
      monocytes/macrophages infiltrating the graft (P < 0.05). CONCLUSIONS: Localized
      PD-L1.Ig expression in donor hearts attenuates acute allograft rejection in a rat
      model. The effect is additive to that of a subtherapeutic regimen of CsA. These
      results suggest that targeting of PD-1 by gene therapy may inhibit acute cardiac
      allograft rejection in vivo.

PMID- 17198269
TI  - Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect
      allospecificity: Potential reagents to promote donor-specific transplantation
      tolerance.
AB  - BACKGROUND: Harnessing naturally arising CD4+ CD25+ regulatory T cells (Tregs)
      for potential adoptive cell therapy is hampered by their innate autoreactivity
      and their limited number. METHODS: CD4+ CD25+ Tregs were purified from peripheral
      blood of human leukocyte antigen (HLA) DR1*0101+ A2- individuals, and stimulated
      with autologous monocyte-derived dendritic cells (DCs). RESULTS: Here we show
      that CD4+ CD25+ Tregs specific for an HLA A2 (103-120) peptide can be selected
      from the peripheral blood CD4+ CD25+ T cell population of a healthy individual
      and detected using a tetramer comprised of HLA DRB1*0101 and the A2 peptide. The
      selected cells can be expanded substantially (i.e., a 1600-fold increase over a
      two-week period) by T-cell receptor (TCR) stimulation and high-doses of
      interleukin-2 (IL-2). The CD4+ CD25+Tregs with indirect allospecificity for the
      A2 peptide showed more potent antigen-specific suppression than polyclonal CD4+
      CD25+ Tregs. CONCLUSIONS: These data may pave the way for clinical studies using
      CD4+ CD25+ Tregs with indirect allospecificity as therapeutic reagents for the
      induction of donor-specific transplantation tolerance.

PMID- 17198271
TI  - Targeting acute allograft rejection by immunotherapy with ex vivo-expanded
      natural CD4+ CD25+ regulatory T cells.
AB  - BACKGROUND: Natural CD4CD25 regulatory T (Treg) cells have been implicated in
      suppressing alloreactivity in vitro and in vivo. We hypothesized that
      immunotherapy using ex vivo-expanded natural Treg could prevent acute allograft
      rejection in mice. METHODS: Natural CD4+ CD25+ Treg were freshly purified from
      naive mice via automated magnetic cell sorter and expanded ex vivo by anti
      CD3/CD28 monoclonal antibody (mAb)-coated Dynabeads. Suppression was assayed in
      vitro by mixed lymphocyte reaction and in vivo by targeting cardiac allograft
      rejection. Survival of Treg or effector T (Teff) cells after adoptive transfer in
      vivo was tracked by flow cytometry and all allografts were examined by histology
      and immunohistochemistry. RESULTS: By day nine in culture, 26.6+/-5.3-fold of
      expansion was achieved by co-culture of fresh natural Treg with anti-CD3/CD28 mAb
      coated Dynabeads and interleukin-2. Ex vivo-expanded Treg exerted stronger
      suppression than fresh ones towards alloantigens in vitro and prevented CD4 Teff
      mediated but only delayed CD4+/CD8+ Teff-mediated heart allograft rejection in
      Rag-/- mice. Long-term surviving allografts showed no signs of acute or chronic
      rejection with graft-infiltrating Treg expressing CD25 and FoxP3. Infused Treg
      persisted and expanded long-term in vivo and trafficked through the peripheral
      lymphoid tissues. CD25 expression was dynamic in vivo: maintained CD25 expression
      on Treg was indicative for the preservation of allosuppression, while
      significantly enhanced CD25 expression on CD4+ effector T cells was most likely
      associated with T-cell expansion and graft rejection. CONCLUSIONS: Therapeutic
      use of ex vivo-expanded natural CD4+ CD25+ Treg may be a feasible and nontoxic
      modality for controlling allograft rejection or perhaps inducing allograft
      tolerance.

PMID- 17198270
TI  - The impact of transforming growth factor-beta1 gene polymorphism on end-stage
      renal failure after heart transplantation.
AB  - BACKGROUND: Nephrotoxicity is a major side effect of calcineurin inhibitors
      (CNI). Earlier we reported 8% of our heart transplant recipients reaching end
      stage renal failure (ESRF). Now, with an extended follow up of 20 years, we re
      evaluated the development of ESRF and studied its influence on survival and the
      impact of polymorphisms in codon 10 and 25 of the promoter region of transforming
      growth factor (TGF)-beta on the risk of ESRF. METHODS: In all, 465 patients were
      transplanted between June 1984 and June 2005. All were on maintenance CNI
      treatment. Development of ESRF was studied in 402/465 (86.5%) patients surviving
      at least one year. Their median follow up was eight years, total observation time
      of 3,414 years. TGF-beta polymorphisms in codon 10 (Leu to Pro) and codon 25 (Arg
      to Pro) were analyzed with real-time polymerase chain reaction in a cohort of 237
      patients, with an observation time of 2,329 years. RESULTS: Ten-year survival of
      patients surviving at least one year was 58.5%. Seventy-three patients (18.2%)
      developed ESRF. Dialysis-free survival was 60% at 15 years. The relative risk for
      ESRF in Pro carriers was 2.9 (CI 1.5-5.8) compared to patients with the Leu/Leu
      genotype (P = 0.002), while Pro carriers had a RR of 2.6 (CI 1.4-4.8) compared to
      the Arg/Arg25 genotype (P = 0.002). Survival of patients with ESRF was 1.5 years
      (median). CONCLUSION: We found a highly significant association between TGF-beta
      polymorphisms and CNI induced ESRF after heart transplantation (HTx). Pro
      carriers of either codon 10 or 25 had a 2.6 to 2.9 times increased risk of
      developing ESRF. As ESRF after HTx results in high mortality rates these patients
      should no longer receive CNI-based immunosuppression.

PMID- 17198272
TI  - Immature syngeneic dendritic cells potentiate tolerance to pancreatic islet
      allografts depleted of donor dendritic cells in microgravity culture condition.
AB  - BACKGROUND: Previously we showed that pancreatic islets cultured for seven days
      in rotating bioreactors survived for >100 days in allogeneic recipients without
      immunosuppression. This survival coincided with almost complete elimination of
      "passenger" donor dendritic cells (DCs). Herein, we examined the necessity of DCs
      in the generation of CD4+ CD25+ T regulatory (Treg) cells. METHODS: Allogeneic
      fresh islets or islets cultured for three days in bioreactors were transplanted
      to streptozotocin-induced diabetic Balb/c(stat4 -/-) as well as signal
      transducers and activators of transcription (Stat)4-deficient Balb/c(stat6 -/-)
      or Balb/c(stat4 -/-) mice. Some Balb/c recipients of fresh islet allografts were
      also treated with a tolerogenic protocol of anti-CD40 Ligand MR1 mAb and CTLA4Ig.
      RESULTS: Islet allografts cultured for three days in bioreactors survived >100
      days in all Balb/c(stat4 -/-) recipients and in 56% of Balb/c(stat6 -/-)
      recipients, but in none of the Balb/c recipients; the same recipients rejected
      fresh islet allografts. Purified T cells from long-term surviving Balb/c(stat4 -/
      ) recipients failed to transfer tolerance to SCID recipients of donor-type fresh
      islet allografts. In contrast, MR1/CTLA4Ig therapy induced tolerance to fresh
      islet allografts and their T cells adoptively transferred tolerance. When Balb/c
      or Balb/c(stat4 -/-) recipients of bioreactor-cultured islets were injected
      intravenously with immature syngeneic DCs, they became tolerant and developed
      potent alloantigen-specific CD4+ CD25+ Treg cells expressing Foxp3. CONCLUSION:
      Allogeneic islets depleted of donor DCs by culture in bioreactors have almost
      twofold better acceptance in Balb/c(stat4 -/-) than in Balb/c(stat6 -/-) mice,
      but lack Treg cells. Additional injection of host immature DCs improves tolerance
      in Balb/c and Balb/c(stat4 -/-) recipients by inducing potent CD4+ CD25+ Treg
      cells.

PMID- 17198273
TI  - Isolation of regulatory T cells in the skin of a human hand-allograft, up to six
      years posttransplantation.
AB  - BACKGROUND: A bilateral hand allotransplantation was performed in a patient six
      years ago. Whereas skin is known to be highly immunogenic, grafts have been well
      accepted up to now. Therefore, here we investigated the putative presence of
      regulatory T cells in the graft. METHODS: Skin biopsies were performed at
      different time points and analyzed by immunochemistry. T cells were initially
      expanded with interleukin (IL)-2. In the latter biopsy, skin was directly
      analyzed by reverse-transcriptase polymerase chain reaction without any culture.
      RESULTS: When tested against donor mononuclear cells, donor-primed skin T cells
      demonstrated unresponsiveness and inhibited donor-directed blood T cell
      alloresponse. Moreover, their T-cell receptor-Vbeta repertoire was skewed, in
      contrast to that of peripheral blood T cells. Retrospectively, nuclear FoxP3
      expression in skin was measured by immunohistochemistry and was found positive at
      that time, but appeared to increase with time. This result was supported by the
      measurement of FoxP3 messenger RNA (mRNA) expression in the latter fresh biopsy,
      which showed higher levels than that of blood, together with no expression of
      perforin mRNA, but increased expression of transforming growth factor-beta and IL
      10. No FoxP3 mRNA expression was found in the contralateral leg, due to the
      absence of T cell infiltrate. CONCLUSION: This study shows the presence of the
      FoxP3 marker, in a well accepted human composite tissue allograft, up to six
      years posttransplantation. Because a suppressive cytokinic profile was also
      detected intragraft, in the absence of perforin mRNA expression, our data suggest
      that regulatory T cells could play a role in the long-term survival of this
      allograft.

PMID- 17198274
TI  - CD20+ lymphocytes in renal allografts are associated with poor graft survival in
      pediatric patients.
AB  - BACKGROUND: The presence of CD20+ lymphocyte renal allograft infiltrates has been
      associated with steroid-resistant rejection and poor graft survival. We
      quantified the number of CD20+ lymphocytes in renal allograft biopsies and
      correlated the results with graft survival. We also determined the relationships
      between CD20+ lymphocytes and acute cellular rejection versus antibody-mediated
      rejection. METHODS: We examined 45 biopsy samples from 31 pediatric patients
      biopsied for suspicion of rejection from November 2001 to November 2004.
      Immunohistochemical staining for CD20 and C4d was performed on all biopsies;
      CD20+ cell density per high-power field (hpf) was determined for each core.
      Patient graft status was followed postbiopsy and documented for graft survival or
      failure using the cutoff date of December 31, 2005. RESULTS: Patients with 2-10
      and 11-100 CD20+ cells/hpf had worse graft survival in Kaplan-Meier analysis with
      a hazard ratio 4.56 (CI 1.07-19.35) two years postbiopsy compared to those with 0
      1 cells/hpf (P = 0.02). The presence of CD20+ lymphocytes was significantly
      associated with acute cellular rejection (P = 0.0001) and not associated with
      antibody-mediated rejection (P = 0.16). Receiver-operating curve analysis
      confirmed > or =3 cells/hpf correlating with acute cellular rejection, yielding
      sensitivity 90% and specificity 76%. CONCLUSIONS: This study shows a significant
      4.5-fold risk of graft failure at two years postbiopsy with presence of > or =2
      CD20+ cells/hpf. Moreover, > or =3 CD20+ lymphocytes were highly associated with
      acute cellular rejection. They may be functioning as professional antigen
      presenting cells in the graft. In steroid-refractory cellular rejections,
      therapies that target B cells may prolong graft survival.

PMID- 17198275
TI  - Disparate distribution of 16 candidate single nucleotide polymorphisms among
      racial and ethnic groups of pediatric heart transplant patients.
AB  - BACKGROUND: Allograft failure in African-Americans remains higher than in
      Caucasians. Single nucleotide polymorphisms (SNPs) have been associated with
      altered allograft outcomes. METHODS: In this multi-center study we compared SNP
      frequencies in 364 pediatric heart recipients from three ethnic/racial groups:
      Caucasian (n = 243), African-American (n = 39), and Hispanic (n = 82). The target
      genes were: tumor necrosis factor-alpha, interleukin (IL)-10, IL-6, interferon
      (IFN)-gamma, vascular endothelial growth factor (VEGF), transforming growth
      factor-beta1, Fas, FasL, granzyme B, ABCB1, CYP3A5. RESULTS: Compared to
      Caucasians, African-Americans exhibited a higher prevalence of genotypes
      associated with low expression of IFN-gamma (24% vs. 45.7%, P < 0.001) and IL-10
      (33% vs. 57.1%, P = 0.052). African-Americans also exhibited an increased
      prevalence of high IL-6 (82.9% vs. 38.1%; P < 0.001). VEGF -2578 C/C and -460 C/C
      genotypes were found more frequently in African-Americans and Hispanics as
      compared to Caucasians (P < 0.001). G/G genotype of Fas and T/T genotype of FasL
      were expressed more often by African-American recipients. The prevalence of
      Granzyme B (-295A/G) genotype was differentially distributed in the three groups.
      Compared with Caucasians, African-Americans were twice as likely to carry the
      ABCB1 2677 G/G genotype (78.6% vs. 33.7%, P < 0.0025), and they were more
      frequent carriers of the CYP3A5 *1/*1 genotype (35.7% vs. 0.6% in Caucasians and
      7.2% in Hispanics; P < 0.001). CONCLUSION: African-Americans have a genetic
      background that may predispose to proinflammatory/lower regulatory environment,
      reduced drug exposure and immunosuppressive efficacy. In this ongoing multicenter
      study, these gene polymorphisms differences among ethnic/racial groups are being
      documented so that therapeutic strategies can be devised to optimize outcomes for
      pediatric transplant recipients.

PMID- 17198276
TI  - Protection of renal ischemia injury using combination gene silencing of
      complement 3 and caspase 3 genes.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury occurs in clinical kidney
      transplantation, which results in graft dysfunction and rejection. It has been
      documented that I/R injury is associated with complement activation and renal
      cell apoptosis. The purpose of this study was to develop a strategy to prevent
      I/R injury using small interfering RNA (siRNA) that target complement 3 (C3) and
      caspase 3 genes. METHODS: siRNA-expression vectors were constructed to target C3
      and caspase 3 genes. Gene silencing efficacy was assessed using real-time
      polymerase chain reaction. In vivo gene silencing was performed by hydrodynamic
      injection with C3 and caspase 3 siRNA. Renal I/R injury was induced through
      clamping the renal vein and artery for 25 min. I/R injury was evaluated using
      kidney histopathology, blood urea nitrogen (BUN), serum levels of creatinine, and
      survival. RESULTS: Effective gene silencing was first confirmed in vitro. Notably
      upregulated expression of C3 and caspase 3 genes was observed from 2 to 48 hr
      after I/R injury, which were effectively and specifically inhibited by C3 and
      caspase 3 siRNA. In comparison with control mice, serum levels of creatinine and
      BUN were also significantly decreased in C3 and caspase 3 siRNA-treated mice.
      Furthermore, the therapeutic effect of siRNA was assessed in a severe, lethal I/R
      injury experiment, in which siRNA treatment significantly reduced mortality.
      Tissue histopathology showed an overall reduction in injury area in siRNA-treated
      mice. CONCLUSIONS: This is the first demonstration that renal I/R injury can be
      prevented through silencing the complement gene and apoptosis gene, highlighting
      the potential for siRNA-based clinical therapy.

PMID- 17198277
TI  - Increased immunosuppression, not anticoagulation, extends cardiac xenograft
      survival.
AB  - BACKGROUND: Cardiac xenograft function is lost due to delayed xenograft rejection
      (DXR) characterized by microvascular thrombosis and myocardial necrosis. The
      cause of DXR is unknown but may result from thrombosis induced by antibody
      mediated activation of endothelial cells and/or by incompatibilities in
      thromboregulatory interactions. METHODS: To examine these issues, a series
      (Groups 1-6) of previous transgenic CD46 pig-to-baboon heterotopic cardiac
      transplants were reanalyzed for baseline immunosuppressive levels, graft survival
      and infectious complications with and without systemic anticoagulation. Groups 1
      4 received low dose tacrolimus and sirolimus maintenance therapy, with
      splenectomy, anti-CD20 and daily alpha-Gal polymer. Group 1 recipients received
      no anticoagulation. Groups 2-4 were anticoagulated with aspirin and Plavix,
      Lovenox, or Coumadin, respectively. Group 5 was treated with Lovenox and high
      dose tacrolimus and sirolimus maintenance therapy. Group 6 recipients received no
      postoperative anticoagulation but the same immunosuppression as group 5. RESULTS:
      Median survival (15-22 days) within groups 1-4 was not significantly different.
      At rejection all tissues exhibited microvascular thrombosis, coagulative necrosis
      and similar levels of platelet and fibrin deposition. Groups 5 and 6 median
      survival (76 days) was significantly increased compared to groups 1-4. There was
      no significant difference in median survival between Lovenox treated recipients
      (68 days) and anticoagulant free recipients (96 days). Rejected tissues showed
      vascular antibody deposition, microvascular thrombosis, and myocyte necrosis.
      CONCLUSION: Significant prolongation in xenograft survival is achieved by
      improved immunosuppression. These results suggest that ongoing immune responses
      remain the major stimulus for DXR.

PMID- 17198279
TI  - Medical education reform: is it time for a modern flexner report?

PMID- 17198278
TI  - Conversion to sirolimus in renal transplant recipients with skin cancer.

PMID- 17198282
TI  - Establishing procedures for institutional oversight of stem cell research.
AB  - Academic health centers (AHCs), which are at the forefront of stem cell research,
      need to establish institutional stem cell research oversight committees (SCROs)
      to comply with 2005 National Academy of Sciences (NAS) recommendations and to
      establish public trust in this sensitive research. Institutional review boards
      (IRBs) typically lack the expertise and time to adequately review the specific
      ethical issues raised by stem cell research. To assure careful, timely, and
      coordinated review of the science and ethics of stem cell protocols, AHCs need to
      address many practical procedural issues, such as SCRO membership, quorum,
      conflicts of interest, and procedures for protocol review. The SCRO committee at
      the University of California San Francisco (UCSF), established in 2003, has
      developed detailed policies and procedures on these issues. The UCSF SCRO has
      broad scientific expertise and uses ad hoc reviewers to strengthen the review
      process. Studies receiving full SCRO review have three lead reviewers: a
      scientist, a reviewer with ethics expertise, and a public representative. Studies
      introducing human stem cells into nonhuman blastocysts receive full review, even
      if the stem cells are anonymized. Some protocols are eligible for expedited
      review. The SCRO neither replaces nor duplicates review by the IRB and
      institutional animal care and use committees. Other AHCs can draw on the UCSF
      experience when developing their own policies and procedures for stem cell
      research oversight.

PMID- 17198283
TI  - Rejuvenating a foundering institutional review board: one institution's story.
AB  - This report recounts one institution's experience in the fundamental
      reorganization of its institutional review board (IRB). With an appropriate
      approach, organizational structure, and ethos, the goals of research participant
      safety, regulatory compliance, and efficiency are not in conflict but, rather,
      mutually reinforcing. These important goals were realized because all aspects of
      the IRB reorganization were guided by and measured against five related
      principles: (1) expertise, (2) service, (3) credibility, (4) efficiency, and (5)
      accountability. This medium-sized academic IRB was successfully reorganized to
      increase the scrutiny of protection of human subjects and to promote efficiency
      and investigator services. On average, the office returned expedited submissions
      to investigators with approvals or queries within two working days of submission.
      On submissions requiring full committee review, letters and faxes were issued to
      investigators within 48 hours of committee meetings. This turnaround time
      (combined with a nine-day premeeting submission requirement) meant that
      investigators who had submitted new studies for full committee review received an
      approval, request for modifications, queries for more information, or disapproval
      within 11 days from the reorganized IRB. In contrast, an Office of the Inspector
      General study noted that IRBs in academic medical centers typically report
      decisions within an average of 37 days. The reforms included mechanical and
      operational changes within office procedure, a robust educational program for
      committee members, and a revamped IRB office staff that decreased the total
      number of office employees from five to four but that increased educational
      levels and skills of the staff members.

PMID- 17198285
TI  - Incorporating principles and practical wisdom in research ethics education: a
      preliminary study.
AB  - PURPOSE: Researchers are faced with daily ethical decisions that are subtle and
      nuanced. However, research ethics training has primarily focused on formal
      guidelines, general ethical principles, and historically noteworthy cases of
      research abuse, which may not prepare researchers to respond to everyday dilemmas
      in research. This study characterized researchers' responses to ethical dilemmas
      with the goal of aligning research ethics education programs with the demands of
      practice. METHOD: As a preliminary study, the authors conducted 23 semistructured
      interviews with senior researchers and research administrators engaged in
      research with human subjects at the University of Washington and affiliated
      institutions in 2004. Transcripts were reviewed for research conflicts and
      strategies used to resolve conflicts identified by participants. RESULTS:
      Participants referenced two distinct methods of reasoning when faced with
      conflicts: formal guidelines and practical wisdom. Formal guidelines include
      established goals, boundaries, and absolutes. Practical wisdom, an Aristotelian
      concept involving intuitions developed through experience, facilitates responses
      to everyday dilemmas and new situations. Developing practical wisdom requires
      researchers to calibrate their own intuitions about right and wrong. Three
      practices were reported to contribute to this development: self-reflection,
      sincere skepticism, and open dialogue with colleagues. CONCLUSIONS: These
      reflections from the senior researchers suggest a need to expand the scope of
      ethics education programs to include a focus on the development of researchers'
      pragmatic decision making in addition to the formal rules that govern research.
      Further research should explore effective educational and institutional
      strategies that can foster researchers' development in ethical decision making
      and conduct.

PMID- 17198286
TI  - University of Minnesota medical school.

PMID- 17198287
TI  - Inventors as investigators: the ethics of patents in clinical trials.
AB  - CONTEXT: The Bayh-Dole Act and renewed emphasis on translational research have
      stimulated patenting activities at universities. PURPOSE: To examine how
      different institutions manage possible patent-related conflicts of interest in
      human subjects research, and to provide an ethical analysis and recommendations.
      METHOD: Policies of nine major professional organizations, 13 of the largest
      recipients of federal biomedical funding in the United States and Canada, and 17
      biomedical journals were canvassed. Disagreements in policies were used as the
      basis for analyzing the ethics of inventorship in clinical trials. RESULTS:
      Policies varied along three lines. First, some policies did not define patent
      inventorship as a potential conflict of interest. Second, some of those that did
      define it as such used licensing as a trigger for conflict of interest
      management. Third, several policies imposed presumptive restrictions on an
      investigator's participation in a trial involving his or her invention.
      CONCLUSIONS: The author defends on ethical grounds restrictive policies on patent
      holding in clinical trials and rejects objections to restrictive policies. The
      author recommends five policies: (1) any related patent holding should always be
      disclosed to IRBs and research subjects, (2) investigators who hold conflicting
      patents should be presumptively barred from certain activities in a study, (3)
      institutional interests in patents should be managed and disclosed to research
      subjects, (4) IRBs should also be informed of an investigator's filed (not just
      held) patents on an experimental agent, and (5) the stringency of policies should
      be adjusted according to a patent's earning potential and the risk associated
      with a study.

PMID- 17198288
TI  - The vitamin K deficiency.

PMID- 17198289
TI  - Educational approaches to the responsible conduct of clinical research: an
      exploratory study.
AB  - PURPOSE: To identify best practices in education related to the responsible
      conduct of clinical research (RCCR). METHOD: American Society for Bioethics and
      Humanities (ASBH) members involved with teaching RCCR were asked to complete an
      online survey, followed by an in-depth telephone interview. The online survey
      asked about respondents' RCCR teaching, trainees, and institutional context. The
      phone interview involved discussions about teaching strategies, institutional
      context, and needs. The study was conducted between 2003 and 2005. RESULTS: Forty
      eight respondents to the online survey indicated a breadth of topics being
      covered in RCCR curricula; 35 respondents indicated that their RCCR teaching
      applied toward institutional RCCR requirements. Among the 21 instructors
      interviewed, many described a wide variety of teaching responsibilities.
      Recommended teaching strategies included fostering interactive discussion, using
      skills-based exercises such as designing IRB applications, accommodating
      students' individual interests in curriculum design, involving experienced
      researchers, involving trainees early in their careers as well as requiring
      continuing education, and designing a curriculum with a clear view of educational
      objectives. Interviewees described the institutional supports they needed, and
      they noted that insufficient support sometimes undermines RCCR teaching goals.
      Participants generally agreed that RCCR education should be required.
      CONCLUSIONS: Strong agreement among participants concerning recommended
      strategies for teaching RCCR provides useful, if provisional, guidance to
      instructors and institutions charged with providing such training. The study
      suggests a need for substantial investments in RCCR training, studying outcomes,
      and developing mechanisms to ensure the quality of instruction.

PMID- 17198292
TI  - The trouble with assessing students' professionalism: theoretical insights from
      sociocognitive psychology.
AB  - The academic literature on professionalism assessment in medical education is
      burgeoning, and its focus has primarily been on the assessment of professional
      behaviors. Consequently, the attitudinal elements of professionalism have largely
      been ignored in the literature. As a result, educators chiefly rely on
      professional behavior alone as the primary measure for professionalism without
      giving proper consideration to students' underlying attitudes. Using theoretical
      insights from sociocognitive psychology, this viewpoint article begins by
      discussing the relationship between attitudes and behaviors. It suggests that
      attitudes are poor predictors of behavior when external constraints, such as
      social pressure to behave in a particular way, are strong. It continues with a
      critical examination of the phenomenon of "faking it"--students faking
      professional behaviors to garner positive reactions from observers. This practice
      is contrasted with students who at times behave unprofessionally in response to
      social pressures or other contextual components, despite having professional
      attitudes. So, in using behavioral assessment alone, we may pass students with
      professional behaviors but unethical attitudes and fail students with
      unprofessional behaviors but ethical attitudes. Guided by a sociocognitive model
      of behavioral explanation, the article ends with some practical recommendations
      for coupling observation with conversation to assess students' professional
      behaviors and their attitudes more fairly.

PMID- 17198290
TI  - Professionalism in modern medicine: does the emperor have any clothes?
AB  - The virtues that constitute medical professionalism have been aptly described in
      multiple position statements from professional organizations and individuals.
      These professional virtues depend on particular moral community traditions to
      undergird and sustain them. Attempts to ground these virtues in narratives
      intrinsic to medical practice--in the moral consensus of physicians or patients,
      in the self-regulating character of medicine as a profession, in the Hippocratic
      tradition, or in the physician-patient encounter--have been unsuccessful. Modern
      medicine must, therefore, look outside its own methodological and clinical
      practices for grounding narratives sufficient to sustain the professional virtues
      set forth in the recently published professionalism statements. These
      professionalism statements are written to capture consensus, and they rarely
      acknowledge the external moral traditions on which the virtues depend, because
      doing so would, in a pluralistic culture, entail the risk of moral disagreement
      and division. The authors argue that meaningful education in professionalism must
      look beyond the consensus statements and deeply engage the particular cultural
      traditions external to the practice of medicine that sustain the professional
      virtues. Medical professionalism curricula should embody an open pluralism,
      giving voice to diverse moral communities, encouraging critical self-exploration
      and discussion about the truth claims of these communities, and, if possible,
      facilitating the integration of students' professional development with their
      ongoing participation in these communities. Engagement with and participation in
      these sustaining moral communities would promote the cultivation of virtue
      capable of withstanding the economic and social threats to professionalism that
      are inherent in modern medical practice.

PMID- 17198293
TI  - A web-based system for students to document their experiences within six core
      competency domains during all clinical clerkships.
AB  - The authors describe the design and implementation of a new Web-based system that
      allows students to record important features of their clinical encounters during
      all 10 required clinical clerkships, document their learning experiences in six
      major competency domains, and generate detailed real-time reports for themselves
      and their clerkship directors. A new Web-based system, DMEDS (Dartmouth Medical
      Encounter Documentation System), accepts input from computers and PDAs. Its
      design permits students to describe their patients, learning sites, interactions
      with preceptors, and important aspects of their clinical encounters in all of our
      medical school's competency domains. Using a common format for all required
      clerkships, clerkship directors select specific items most relevant to their
      clerkships from a common menu and set learning targets for specific diagnoses and
      clinical skills. This new system was designed in the fall of 2003, tested in the
      spring of 2004, and implemented in all clerkships for the 2004 to 2005 academic
      year. During the first full academic year that DMEDS was used, students
      documented nearly 32,000 discrete student-patient-preceptor encounters, an
      average of between 21 and 120 clinical encounters per Year 3 clerkship.
      Highlights of the analysis of these initial data include the following: (1)
      insights into how educational targets are set, (2) the extent of site-to-site
      variation in clerkship experiences, (3) the epidemiology of patients' declining
      student involvement, and (4) student experiences in and understanding of the
      newer competency domains.DMEDS can be used in all clinical clerkships and can
      address student experiences in all competency domains. It provides substantial
      value to students, clerkship directors, preceptors, and medical school
      administrators. As secondary benefits, the authors found that DMEDS facilitates
      educational research and is readily adapted for use in residency and fellowship
      programs as well. Student feedback highlights the need to pay close attention to
      the time invested by students documenting their clinical encounters. Course
      directors must ensure that the benefits to students (such as knowledge of meeting
      learning targets and preceptors providing direct feedback to students) are
      transparent. Finally, for other schools contemplating the change to a competency
      based curriculum with the use of a clinical encounter documentation system, the
      time required for both students and faculty to adopt and fully engage these major
      educational culture shifts seems to be at least several years.

PMID- 17198294
TI  - Comparing problem-based learning with case-based learning: effects of a major
      curricular shift at two institutions.
AB  - PURPOSE: Problem-based learning (PBL) is now used at many medical schools to
      promote lifelong learning, open inquiry, teamwork, and critical thinking. PBL has
      not been compared with other forms of discussion-based small-group learning. Case
      based learning (CBL) uses a guided inquiry method and provides more structure
      during small-group sessions. In this study, we compared faculty and medical
      students' perceptions of traditional PBL with CBL after a curricular shift at two
      institutions. METHOD: Over periods of three years, the medical schools at the
      University of California, Los Angeles (UCLA) and the University of California,
      Davis (UCD) changed first-, second-, and third-year Doctoring courses from PBL to
      CBL formats. Ten months after the shift (2001 at UCLA and 2004 at UCD), students
      and faculty who had participated in both curricula completed a 24-item
      questionnaire about their PBL and CBL perceptions and the perceived advantages of
      each format RESULTS: A total of 286 students (86%-97%) and 31 faculty (92%-100%)
      completed questionnaires. CBL was preferred by students (255; 89%) and faculty
      (26; 84%) across schools and learner levels. The few students preferring PBL
      (11%) felt it encouraged self-directed learning (26%) and valued its greater
      opportunities for participation (32%). From logistic regression, students
      preferred CBL because of fewer unfocused tangents (59%, odds ration [OR] 4.10, P
      = .01), less busy-work (80%, OR 3.97, P = .01), and more opportunities for
      clinical skills application (52%, OR 25.6, P = .002). CONCLUSIONS: Learners and
      faculty at two major academic medical centers overwhelmingly preferred CBL
      (guided inquiry) over PBL (open inquiry). Given the dense medical curriculum and
      need for efficient use of student and faculty time, CBL offers an alternative
      model to traditional PBL small-group teaching. This study could not assess which
      method produces better practicing physicians.

PMID- 17198295
TI  - Just be yourself.

PMID- 17198296
TI  - A proposal for teaching basic clinical skills for mastery: the case against
      vertical integration.
AB  - The authors argue that medical school faculty should (1) make a distinction among
      competencies that they feel need to be taught for mastery (i.e., at a level of
      proficiency expected from a practicing physician) and those that should be taught
      at lower levels of proficiency, and (2) impart the former competencies in single
      teaching units. The authors propose that the skills that students should be
      expected to master include patient interviewing, physical examination, patient
      counseling on health promotion and disease prevention (HP/DP), and self-directed
      learning. The concepts of a hypothetical teaching unit that aims to impart these
      skills are described. By the end of this unit, the students would be expected to
      (1) examine simulated and real patients to detect risk indicators and physical
      findings for the diseases that are the most common causes of death in the
      patient's gender and age group, and to look for risk indicators and physical
      findings for diseases where early diagnosis and treatment have been shown to
      reduce mortality for such patients, and (2) provide counseling for lifestyle
      changes and future clinical examinations. The authors believe that the objective
      of acquiring an ability to counsel a patient on HP/DP at the level of competence
      of a practicing physician will motivate students to acquire the skills of patient
      interviewing, physical examination, and self-directed learning more effectively
      than would a succession of reinforcements of these subjects throughout the
      curriculum.

PMID- 17198298
TI  - Medicine and the arts. Two cartoons on disabilities by John Callahan. Commentary.

PMID- 17198299
TI  - Attitudes of preclinical and clinical medical students toward interactions with
      the pharmaceutical industry.
AB  - PURPOSE: Medical school is a critical time for physicians in training to learn
      the professional norms of interacting with the pharmaceutical industry, yet
      little is known about how students' attitudes vary during the course of training.
      This study sought to determine students' opinions about pharmaceutical industry
      interactions with medical students and whether these opinions differ between
      preclinical and clinical students. METHOD: The authors surveyed medical students
      at Harvard Medical School (HMS) from November 2003 through January 2004 using a
      six-question survey. The authors then analyzed how responses differed among the
      classes. RESULTS: Out of 723 questionnaires, 418 were returned--an overall
      response rate of 58%. A total of 107 (26%) students believed that it is
      appropriate for medical students to accept gifts from pharmaceutical companies,
      and 76 (18%) agreed that the medical school curriculum should include events
      sponsored by the pharmaceutical industry. Many students--253 (61%)--reported that
      they do not feel adequately educated about pharmaceutical industry-medical
      professionals' interactions. Preclinical and clinical students had similar
      opinions for the majority of their responses. Finally, students who reported
      feeling better educated about pharmaceutical industry interactions tended to be
      less skeptical of the industry and more likely to view interactions with the
      industry as appropriate. CONCLUSIONS: Students' opinions about interactions with
      the pharmaceutical industry were similar between preclinical and clinical
      students, suggesting that the current medical school experience may have limited
      impact on students' views about interactions with the pharmaceutical industry.

PMID- 17198300
TI  - The predictive validity of the MCAT for medical school performance and medical
      board licensing examinations: a meta-analysis of the published research.
AB  - PURPOSE: To conduct a meta-analysis of published studies to determine the
      predictive validity of the MCAT on medical school performance and medical board
      licensing examinations. METHOD: The authors included all peer-reviewed published
      studies reporting empirical data on the relationship between MCAT scores and
      medical school performance or medical board licensing exam measures. Moderator
      variables, participant characteristics, and medical school performance/medical
      board licensing exam measures were extracted and reviewed separately by three
      reviewers using a standardized protocol. RESULTS: Medical school performance
      measures from 11 studies and medical board licensing examinations from 18
      studies, for a total of 23 studies, were selected. A random-effects model meta
      analysis of weighted effects sizes (r) resulted in (1) a predictive validity
      coefficient for the MCAT in the preclinical years of r = 0.39 (95% confidence
      interval [CI], 0.21-0.54) and on the USMLE Step 1 of r = 0.60 (95% CI, 0.50
      0.67); and (2) the biological sciences subtest as the best predictor of medical
      school performance in the preclinical years (r = 0.32 95% CI, 0.21-0.42) and on
      the USMLE Step 1 (r = 0.48 95% CI, 0.41-0.54). CONCLUSIONS: The predictive
      validity of the MCAT ranges from small to medium for both medical school
      performance and medical board licensing exam measures. The medical profession is
      challenged to develop screening and selection criteria with improved validity
      that can supplement the MCAT as an important criterion for admission to medical
      schools.

PMID- 17198301
TI  - Blending education, research, and service missions: the Arkansas model.
AB  - Creating school and community partnerships with academic health centers (AHC)
      offers one strategy for initiating and sustaining broad-based change in health
      systems. This article describes the development, initial evaluation, and current
      iteration of the Arkansas Partners in Behavioral Health Sciences Model, a
      collaboration between personnel from an AHC and K-12 schools to address
      behavioral health issues in children. The model's focus on education, research,
      and service provides an opportunity for AHC faculty and school personnel to
      collaborate to promote mental health in school-aged youth. Quantitative and
      qualitative methods have been used to inform development and confirm
      effectiveness of the program. From 2001 through 2005, more than 2,700 school
      personnel from 72 of the 75 counties in Arkansas participated in more than 30,000
      hours of continuing education. The programs have also targeted students using
      interactive televideo presentations, supplemental classroom curricula, and an
      exhibit in a state science museum, resulting in an outreach to more than 2,500
      youths. Results of longitudinal and randomized studies also show changes in
      knowledge, attitudes, and behaviors. In an era of extraordinary need and finite
      resources for school systems, AHCs are poised to provide the critical link to
      improve the scientific knowledge and understanding of behavioral health
      conditions. The current program targets behavioral health, but AHCs also can
      incorporate other health conditions, scientific topics, and medical interventions
      to provide a important service for the public and to accomplish an important
      mission toward health leadership in the community.

PMID- 17198305
TI  - Redefining early cervical neoplasia: recent progress.
AB  - The classification of cervical precancers has evolved over the past 40 years as
      knowledge concerning the pathogenesis of these human papillomavirus-related
      lesions has expanded. This commentary reviews the current classification scheme
      in light of (1) the historical classification systems and (2) the ability of the
      target epithelium, that is the transformation zone to exhibit varied morphology
      depending on the cell type that is infected with human papillomavirus. The
      evolution in our understanding of preinvasive glandular neoplasia is also
      summarized, with particular attention to so-called superficial (or early)
      adenocarcinoma in situ. In addition, practical issues in the diagnosis and
      management of squamous epithelial lesions, particularly the recognition of
      nonconventional variants and the application of biomarkers, are discussed.

PMID- 17198306
TI  - Respiratory epithelial adenomatoid hamartoma: diagnostic pitfalls with emphasis
      on differential diagnosis.
AB  - In the upper aerodigestive tract, respiratory epithelial adenomatoid hamartoma
      (REAH) is described as a polypoid proliferation of glands lined by ciliated
      respiratory epithelium that seem to invaginate downward into the submucosa while
      maintaining direct continuity with the surface mucosa. The lesion can be confused
      with a variety of benign and malignant entities, including inflammatory polyp,
      inverted schneiderian papilloma, and low-grade sinonasal adenocarcinoma. In
      reviewing the historical, clinical, gross, and histopathologic features of REAH
      and its subtypes, we elucidate how the distinction of REAH with florid mucinous
      metaplasia from low-grade adenocarcinoma can be challenging particularly in the
      setting of small biopsy samples. Diagnostic criteria are reviewed with emphasis
      on key distinguishing characteristics. The significance of this distinction is
      paramount in preventing unwarranted surgery and untoward consequences for the
      patient.

PMID- 17198307
TI  - Postmenopausal hormone replacement therapy: endometrial and breast effects.
AB  - The history of hormone replacement therapy (HRT) dates back to the late 1800s,
      when animal extracts of ovaries were first used. With the development of
      synthetic hormones, widespread use in postmenopausal women extended throughout
      the industrialized world, so that by the late 1900s roughly one-third to one-half
      of all postmenopausal women in the United States and Europe were taking HRT. Two
      events changed the course of use of HRT: the association of an increased rate of
      endometrial carcinoma with estrogen-only HRT and the association of an increased
      breast cancer rate with combined estrogen and progestin HRT. This review explores
      the evidence of the effects of HRT on the endometrium and the breast, with
      emphasis on the pathologic changes.

PMID- 17198308
TI  - New transcription factors in diagnostic hematopathology.
AB  - The transcription factors (TFs) that controls the intricate machinery of
      multistep differentiation and activation programs of the lymphoid system,
      represent a complex array of proteins, whose identification and function has only
      in part been completed. TFs are usually expressed during specific differentiation
      or activation cellular programs, making them interesting tools in diagnostic
      immunohistochemistry. In fact, the specificity of some of these TFs for lineage
      or activation/differentiation passages or their abnormal expression in specific
      disease entity, represents a feature that has been exploited in
      diagnostic/prognostic immunohistochemistry. Bcl-6 was the prototype of this class
      of markers. Currently, the expanding knowledge of the TFs involved in the
      differentiation programs and in the activation processes of T-lymphocyte and B
      lymphocyte in normal and neoplastic conditions and the availability of antibodies
      able to efficiently recognize these TFs in histologic material, represent a
      powerful tool in diagnostic hematopathology. In this review we will consider the
      basic biologic aspects and the applications in hematopathology of some of the
      lymphocyte-related TFs, including Pax5/BSAB, MUM1/IRF4, BOB1, Oct-2, T-bet, and
      FOXP3. This field is rapidly evolving, as witnessed by the ongoing growing number
      of novel TFs with possible diagnostic applications appearing in the literature.

PMID- 17198309
TI  - Perivascular epithelioid cell tumor (PEComa) in the genitourinary tract.
AB  - Perivascular epithelioid cell tumors (PEComas) are mesenchymal tumors composed of
      histologically, immunohistochemically, ultrastructurally, and genetically
      distinctive cells. PEComas have been described in different organs and are
      considered ubiquitous tumors. In this review we discuss recent informations
      related to PEComas in the genitourinary tract.

PMID- 17198310
TI  - p38 MAPK as a potential therapeutic target for inflammatory osteolysis.
AB  - Inflammatory osteolysis is a relatively frequent and incapacitating complication
      of rheumatoid arthritis and other inflammatory diseases, and is induced by
      accelerated osteoclast recruitment and activation in bone under the aegis of
      cytokines produced in the inflammatory environment. The success of antitumor
      necrosis factor-alpha and interleukin-1 therapy in correcting this condition
      highlights the central role of these cytokines in this process. Recent years have
      witnessed a revolution in understanding the molecular mechanism and pathogenesis
      of this family of diseases. It is now clear that p38 mitogen-activated protein
      kinase plays an essential role in the production of proinflammatory cytokines and
      cytokine-induced osteoclastogenesis, thus providing a potential therapeutic
      target for prevention of pathologic bone loss.

PMID- 17198311
TI  - Neural lipofibromatous hamartoma: a report of two cases and review of the
      literature.

PMID- 17198318
TI  - A plea for uniformity, leading to clarity.

PMID- 17198319
TI  - Scaphoid fractures: variation in radiographic views - a survey of current
      practice in the West of Scotland region.
AB  - BACKGROUND: A variation seems to exist between hospitals with regard to the
      initial radiographic assessment of suspected scaphoid fractures. MATERIALS AND
      METHODS: A survey of all acute hospitals in the West of Scotland was carried out
      to ascertain the current practice in the assessment of acute scaphoid fractures.
      Consultant radiologists and consultant orthopaedic surgeons from the same
      hospitals were requested to suggest the minimum number and type of views to be
      ideally performed for a routine scaphoid series. RESULTS: Fourteen hospitals, 85
      consultant orthopaedic surgeons and 60 consultant radiologists were contacted.
      Among the hospitals, 64.3% performed four views and 28.5% performed three views
      for a suspected scaphoid fracture. The commonly performed radiographs were
      lateral with the wrist neutral (85.7%) and postero-anterior oblique in ulnar
      deviation (78.5%). Of the consultant orthopaedic surgeons, 57.5% suggested four
      views, while 33.3% suggested three views. A lateral view with the wrist neutral
      (87.8%) and a postero-anterior view in ulnar deviation (51.5%) were considered
      most useful. Of the consultant radiologists, 68.4% suggested four views and 15.8%
      suggested three views. A lateral view with the wrist neutral (84.2%) and a
      postero-anterior view in ulnar deviation (52.6%) were considered most useful.
      DISCUSSION: A lack of uniformity is found among orthopaedic consultants who
      request scaphoid views, radiographers who perform the views and radiology
      consultants who report on these. We feel a uniform system of radiographic
      evaluation of scaphoid fractures should be introduced, with a standardized number
      and type of views, in all hospitals to increase the familiarity of both
      terminology and visualization.

PMID- 17198320
TI  - How good are emergency department Senior House Officers at interpreting X-rays
      following radiographers' triage?
AB  - OBJECTIVE: To assess the accuracy of Senior House Officers at interpreting plain
      X-rays following their triage by radiographers in an emergency department.
      METHOD: We collected 2593 patients' records by systematic sampling of all those
      seen by emergency physicians between January 2002 and April 2002 (ca 10 000
      patients) in a UK emergency department. The variables recorded included evidence
      of X-ray investigations and, when present, the Senior House Officer's diagnosis,
      the presence (abnormal) or absence of a radiographers red dot and the reference
      standard diagnosis. A separate category of uncertain (inconclusive) was applied
      to the Senior House Officer and reference standard diagnosis where appropriate.
      Diagnostic performance was measured by likelihood ratios with associated pre-test
      and post-test probabilities. RESULTS: Including the uncertain category as
      abnormal gave the following results: there were 967 X-rays and those with a red
      dot had a probability of an abnormality of 80%. Although a further opinion of
      abnormal by a Senior House Officer increased this probability to 89% when they
      overrode the red dot opinion of the radiographer, it was incorrect in 26% of
      cases. CONCLUSION: Currently, the Senior House Officer contributes to the red dot
      system by improving on the radiographer in rates of diagnosis of both abnormal
      and normal X-rays. Further reductions in error rates, however, are unlikely to be
      achieved until there is a change to the existing system. This may ultimately
      involve removing some of the responsibility of X-ray interpretation from the
      Senior House Officer. Any future research should consider the methodological
      issues highlighted by this study.

PMID- 17198321
TI  - Seroprotection against tetanus in patients attending an emergency department in
      Belgium and evaluation of a bedside immunotest.
AB  - BACKGROUND: In most emergency departments, tetanus prophylaxis currently relies
      on vaccination history. Bedside evaluation of tetanus immunity may improve this
      process. OBJECTIVES: (i) To determine the seroprevalence of tetanus immunity;
      (ii) to evaluate the accuracy of vaccination history in assessing tetanus
      immunity; (iii) to identify factors predictive of seroprotection and incorrect
      history. METHOD: In a prospective observational study, tetanus immunity was
      assessed in 784 adults using Tetanos Quick Stick (TQS). A questionnaire was
      completed to obtain vaccination and general histories. Immunity assessed by TQS
      and by vaccination history were compared with anti-tetanus antibody levels
      measured by the enzyme-linked immunosorbent assay (seroprotection threshold >0.15
      IU/ml). RESULTS: Overall, 64.2% of patients were protected according to TQS
      results. Four independent predictors of seroprotection were identified: young
      age, birthplace in Belgium, male sex and occupational medicine consultation. TQS
      performance was good: kappa=0.71, sensitivity 85.3%, specificity 87.2%, positive
      predictive value 92.1% and negative predictive value 77.2%. Seven hundred and
      sixty-two participants responded to the vaccination history: 23.4% said they were
      protected, 22.1% that they were not and 54.5% did not know. History performance
      was poor: kappa=0.27, sensitivity 60.3%, specificity 73.3%, positive predictive
      value 81.8% and negative predictive value 45.8%. Compared with history, TQS
      offered a significantly better sensitivity, negative and positive predictive
      values, but specificity was similar. No predictor of an incorrect history was
      identified. CONCLUSION: Lack of protective immunity against tetanus is frequent
      but poorly evaluated by history taking. Several demographic characteristics are
      good predictors of seroprotection. TQS could be a valuable tool in selected
      patients to improve tetanus prophylaxis in the emergency department.

PMID- 17198322
TI  - European survey on training objectives in disaster medicine.
AB  - OBJECTIVES: As part of the I SEE (Interactive Simulation Exercise for
      Emergencies) project, financially supported by the Leonardo da Vinci Programme
      2000-2006 of the European Commission, a study was planned to assess the type of
      disaster and to establish the tasks to be included in an emergency exercise to be
      developed, according to the possible target groups, physicians, nurses, ambulance
      personnel, dispatchers and first responders. A secondary objective was a
      description of the actual computer-based training situation in the training
      centres. A study involving different actors or target groups has not yet been
      conducted. METHODS: A questionnaire was developed, validated and subsequently
      distributed to the training centres for the different target groups in the
      partner countries. Each partner had to contact and interview the person
      responsible for the training in disaster medicine in the training institution.
      Data entry and analysis was carried out using the SPSS software on Apple
      Macintosh. Apart from descriptive statistics of the variables, differences
      between groups were analysed using analysis of variance and the Kruskal-Wallis
      test. RESULTS: In 75 questionnaires out of a total of 206, the combination of a
      major road traffic accident and a chemical accident was indicated as the first
      choice (36.4%). These priorities were present for the different countries and all
      target groups. Concerning the medical procedures to be included in the training
      exercise, the highest priority was given to medical coordination, medical
      management on site, medical alert procedures, assessment of immediate needs,
      medical resources management, victim transport and protection and safety
      procedures. Only minor differences were noted between countries, different target
      groups and the institutions irrespective of whether they are involved in response
      in case of a major accident or disaster. With regard to the secondary objective,
      27% of the institutions used computer-based training in disaster medicine and, of
      those not using computer-based training, 23% plan its use in the near future.
      CONCLUSIONS: The European centres surveyed, put the emphasis for disaster
      medicine training on a mass casualty scenario. In accordance with this choice,
      prehospital aspects of medical care and management were considered as priorities
      for training. The I SEE project will develop a template and pilot exercise,
      serving all countries and providing team training. Among the institutions
      involved in the survey, a limited number will be invited to participate in the
      formative evaluation of the pilot exercise.

PMID- 17198323
TI  - Asthma fatalities at the Emergency Department of the Singapore General Hospital.
AB  - BACKGROUND: Bronchial asthma is one of the most common chronic diseases in
      Singapore and the prevalence is increasing. Despite this, the worldwide mortality
      rate from asthma has been noted to be low at an average of 2.0 per 100,000 people
      in developed countries such as the United States. Risk factors for fatal asthma
      attacks that have been described include excessive use of short acting beta
      agonists, errors in clinical judgement, poor compliance, psychosocial disorders,
      use of three or more groups of asthma medication and indicators of asthma
      severity. AIM: We aim to study the incidence of asthma deaths occurring in the
      emergency department of a tertiary care hospital in Singapore. METHODS: Of the
      total number of patients at the Department of Emergency Medicine in Singapore
      General Hospital from January 1999 to June 2005, eight fatalities were attributed
      to exacerbation of bronchial asthma. The characteristics of these patients are
      described. RESULTS: A low incidence of asthma-related deaths is found in
      Singapore.

PMID- 17198324
TI  - Long-term outcomes of major trauma without head injury in the West of Scotland:
      pilot case-control study.
AB  - The aim of this study was to identify the outcomes of survivors of blunt major
      trauma (without head injury) 2 years or more following injury. The study uses a
      case-control design, is set in the West of Scotland and includes trauma patients
      treated in Greater Glasgow NHS Board hospitals. Participants consisted of
      patients who had sustained major trauma (injury severity score >15) with little
      or no head injury at least 2 years before assessment, identified from the
      Scottish Trauma Audit Group database, and age and sex-matched controls nominated
      by the index case's general practitioner. Nineteen cases and seven controls
      completed the study from 223 potential cases and 39 potential controls.
      Participants and non-participants had comparable injury severity score,
      probability of survival (Ps) and length of stay. American Medical Association
      impairment scores show survivors were more impaired than controls (25.9 vs 7.4%,
      P=0.043). No differences were observed in Functional Independence Measure (FIM)
      or Community Integration Questionnaire (CIQ) scores, although a type II error is
      possible. Short-form 36 (SF36) Physical Component Summary (PCS) scores of
      survivors showed no difference compared with controls although survivors' PCS
      scores were below UK and US means (P=0.008). SF36 Mental Component Summary (MCS)
      scores of survivors were below those of controls (45.07 vs 56.65, P=0.004) and
      normal values of the UK population (P=0.036). No differences in work status were
      noted, but small sample sizes were used. Non-head-injured survivors of major
      trauma in the West of Scotland have poorer health status (SF36), physically and
      mentally, than the UK population. They have greater impairment, but have an
      employment status comparable to that of the controls. The lack of differences in
      FIM and CIQ scores between survivors and controls may be due to small sample
      sizes.

PMID- 17198325
TI  - Emergency orthopaedic surgery under noninvasive ventilation after refusal for
      general anaesthesia.
AB  - In this observation, we report a novel use of noninvasive positive pressure
      ventilation in the operating room to support ventilation in an acidotic
      hypercapnic patient with severe acute chronic respiratory failure refuted for
      general anaesthesia, operated under spinal anaesthesia for a femoral fracture.
      The feasibility of noninvasive ventilatory assistance during surgery performed
      under regional anaesthesia is reported here. In selected cases, noninvasive
      ventilation can be used in the management of patients with acute or chronic
      respiratory failure requiring an urgent surgical intervention but in whom the
      respiratory status excluded a general anaesthesia.

PMID- 17198326
TI  - Upper airway obstruction in infectious mononucleosis.
AB  - Patients with infectious mononucleosis caused by the Epstein-Barr virus
      frequently present to the accident and emergency department. The most common
      presenting symptoms are fever, fatigue, odynophagia and malaise. Although
      significant airway compromise is rare and occurs in an estimated 1-3.5% of cases,
      it may present as a potentially life-threatening situation demanding immediate
      intervention. We present two such cases and discuss their management.

PMID- 17198327
TI  - Prehospital emergency endotracheal intubation using the Bonfils intubation
      fiberscope.
AB  - Among all prehospital emergency intubations, difficulties occur in 7-10%.
      Furthermore, intubation conditions often worsen when the cervical spine is
      immobilized in trauma patients. We report on six patients in whom the Bonfils
      intubation fiberscope, a reusable, rigid fiberoptic device, was used for
      emergency endotracheal intubation in the field. Three of these patients had an
      anticipated or unanticipated difficult airway: two trauma patients with
      immobilized cervical spine and one patient in cardiac arrest in whom direct
      laryngoscopy failed twice. Endotracheal intubation with the Bonfils intubation
      fiberscope was successful in all cases in the first attempt. The Bonfils
      intubation fiberscope therefore demonstrated its value as an additional airway
      management device in both emergency and prehospital settings.

PMID- 17198328
TI  - Headache: an unusual presentation of aortic dissection.
AB  - The most common presenting symptom of aortic dissection is chest pain - headache
      as the initial manifestation is rare. We report a patient with a history of
      hypertension who presented with severe bifrontal headache, and was found to have
      an acute aortic dissection in the absence of carotid artery dissection. A
      discussion of the atypical presentation and possible pathophysiology follows.

PMID- 17198329
TI  - Necrotizing fasciitis: a challenging diagnosis.
AB  - The objective of the study was to evaluate our recent experience in diagnosis and
      management of necrotizing fasciitis. Records of patients who were diagnosed as
      having necrotizing fasciitis at Al-Ain Hospital in the period between March 2003
      and August 2005 were studied retrospectively with regard to clinical features,
      risk factors, diagnosis, causative organisms, treatment, and outcome. Eleven
      patients, eight of whom were men of low socio-economic status, were studied. The
      median age (range) was 46 (8-65) years. The main risk factor was diabetes
      mellitus in seven patients (64%). The provisional clinical diagnosis was
      incorrect in seven patients (64%). Pure beta-hemolytic streptococcus group A or B
      was the causative organism in five patients (46%). Most of our patients underwent
      multiple surgical debridements with a median range of two (1-11) operations. Two
      patients died (overall mortality rate 18%). High clinical suspicion is essential
      for the diagnosis of necrotizing fasciitis. Accurate early diagnosis, aggressive
      resuscitation, using proper antibiotics, and extensive surgical debridement are
      essential for a favorable outcome.

PMID- 17198330
TI  - Genital foreign bodies: more than the eye can see.
AB  - Genital foreign bodies constitute a diverse but surprisingly common means of
      presentation to emergency departments. Although the presentation usually means
      the initial diagnosis is easily made, we present a case here that stresses the
      importance of attention to history, clinical examination and radiological
      investigation. A 44-year-old gentleman presented with a history of pain and
      discharge from a self-inflicted scrotal wound. Further questioning revealed a
      history of genital foreign bodies, but the full extent of his condition was not
      apparent until plain pelvic radiographs were obtained. The initial management of
      genital foreign bodies follows basic surgical principles. Constricting bands must
      be removed, devitalized tissues debrided and the surgical field extensively
      irrigated. Underlying psychiatric illness may be present and a high index of
      suspicion is required in the initial assessment of such patients. A plain pelvic
      radiograph is recommended to fully identify all foreign bodies present.

PMID- 17198331
TI  - Lactic acidosis in children with acute exacerbation of severe asthma.
AB  - This is a retrospective case series reporting lactic acidosis in four pediatric
      patients with acute severe asthma treated with nebulized beta2-agonists in a
      pediatric intensive care unit of a tertiary care teaching facility. During
      treatment with beta2-agonists, these patients developed lactic acidosis with a
      peak concentration of 5.2 to 13 mmol/l. Lactic acidosis improved within 24 h
      after discontinuation or decrease in the dosage of beta2-agonists. We conclude
      that the intensive use of beta2-agonists for acute severe asthma in children may
      be the primary and significant cause of lactic acidosis.

PMID- 17198332
TI  - Could high blood pressure be the cause of acute spontaneous spinal epidural
      hematoma?

PMID- 17198333
TI  - Anaphylactoid reaction to recombinant tissue plasminogen activator.
AB  - Anaphylactoid reaction to recombinant tissue plasminogen activator for the
      thrombolytic treatment of acute ischemic stroke is an uncommon complication. An
      increased risk of anaphylaxis may be found in patients concomitantly being
      treated with angiotensin-converting enzyme inhibitors, as illustrated by this
      case report describing a patient who experienced an urticaric rash, hypotension,
      tachycardia, orolingual angioedema, and airway obstruction following intravenous
      administration of alteplase. Possible pharmacologic interactions resulting in
      excessive serum bradykinin and subsequent systemic hypersensitivity responses are
      discussed.

PMID- 17198334
TI  - Annual legislative update brings autonomy to the forefront.

PMID- 17198339
TI  - A comprehensive look at the legislative issues affecting advanced nursing
      practice.

PMID- 17198336
TI  - Latest pain relief a combination of new and old.

PMID- 17198341
TI  - Lung cancer diagnosis in primary care.

PMID- 17198344
TI  - Trastuzumab-induced cardiac dysfunction.

PMID- 17198345
TI  - Healthy passive cigarette smokers have increased pulmonary alveolar permeability.
AB  - QUESTION: Does passive smoking have a measurable effect on lung function in
      otherwise healthy subjects? There is current interest concerning passive smoking
      but no objective evidence showing that it has any impact on lung function.
      METHODS: The pulmonary clearance rate of (99m)Tc-DTPA was measured in 21 healthy
      volunteers after inhalation as a radio-aerosol and compared between healthy
      cigarette smokers, passive smokers and non-smokers. All volunteers had normal
      lung function. RESULTS: Clearance half-times in healthy passive smokers (n=5)
      were longer than in healthy smokers (n=6) but clearly shorter compared with
      healthy non-smokers (n=10) with respective mean values of 45.2 (SD 8.3), 24.3
      (8.6) and 80.3 (20) min. CONCLUSION: Passive smoking has a functional impact on
      the lung blood/gas barrier.

PMID- 17198346
TI  - Automated interpretation of PET/CT images in patients with lung cancer.
AB  - PURPOSE: To develop a completely automated method based on image processing
      techniques and artificial neural networks for the interpretation of combined
      [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed
      tomography (CT) images for the diagnosis and staging of lung cancer. METHODS: A
      total of 87 patients who underwent PET/CT examinations due to suspected lung
      cancer comprised the training group. The test group consisted of PET/CT images
      from 49 patients suspected with lung cancer. The consensus interpretations by two
      experienced physicians were used as the 'gold standard' image interpretation. The
      training group was used in the development of the automated method. The image
      processing techniques included algorithms for segmentation of the lungs based on
      the CT images and detection of lesions in the PET images. Lung boundaries from
      the CT images were used for localization of lesions in the PET images in the
      feature extraction process. Eight features from each examination were used as
      inputs to artificial neural networks trained to classify the images. Thereafter,
      the performance of the network was evaluated in the test set. RESULTS: The
      performance of the automated method measured as the area under the receiver
      operating characteristic curve, was 0.97 in the test group, with an accuracy of
      92%. The sensitivity was 86% at a specificity of 100%. CONCLUSIONS: A completely
      automated method using artificial neural networks can be used to detect lung
      cancer with such a high accuracy that the application as a clinical decision
      support tool appears to have significant potential.

PMID- 17198347
TI  - Evaluation of the effect of levocetirizine on nasal mucociliary clearance in
      allergic rhinitis patients by rhinoscintigraphy.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of levocetirizine
      on nasal mucociliary clearance in allergic rhinitis patients using
      rhinoscintigraphy. METHODS: Twenty patients with allergic rhinitis (12 males and
      eight females, mean age 37.7 +/- 10.5 years) were evaluated. All the patients
      received levocetirizine (5 mg x day(-1)) for 4 weeks, and the speed of nasal
      mucociliary clearance was assessed before and after treatment. Twenty healthy
      controls (11 males and nine females, mean age 39.4 +/- 7.8 years) were also
      evaluated. RESULTS: The clearance values obtained for the treated group before
      and after treatment were significantly lower than those of the control group (P =
      0.0001), but there was no significant difference in clearance speeds before and
      after treatment in the patient group (P = 0.444). CONCLUSION: The study
      demonstrated that levocetirizine did not affect the speed of nasal mucociliary
      clearance in allergic rhinitis patients, and that nasal mucociliary clearance can
      easily be evaluated by rhinoscintigraphy.

PMID- 17198348
TI  - [18F]Fluorodeoxyglucose as a memory marker of transient myocardial ischaemia.
AB  - BACKGROUND: Experimental data have shown that glucose utilization increases
      during acute myocardial ischaemia, and may persist for up to 24 h. Whether
      fluorodeoxyglucose (FDG) uptake can be imaged as a memory marker of ischaemia in
      humans is unknown. METHODS: Patients with mild-to-moderate ischaemia on exercise
      single photon emission computed tomography (SPECT) myocardial perfusion imaging
      (MPI) underwent repeat exercise testing within 1-2 weeks. Positron emission
      tomography (PET) was performed after injection of FDG 60 min post-exercise. SPECT
      and PET images were assessed visually, aided by circumferential profile-based
      analysis modified for 'hot-spot' imaging. RESULTS: Twelve men with stress SPECT
      ischaemia (mean age, 69 years; nine with known coronary artery disease) were
      studied. The mean rate-pressure products for the first (SPECT) and second (FDG
      PET) exercise tests were similar (22,841+/-7321 vs. 22,680+/-7393 mmHg x bpm,
      P=NS). Overall, six of 12 patients studied had evidence of FDG uptake. The extent
      of ischaemia on SPECT was similar in FDG positive and FDG negative patients
      (summed difference score 10.6+/-6.9 vs. 8.0+/-1.6, P=NS). All patients with a
      positive FDG scan had uptake in either an ischaemic SPECT region or in a
      territory with known CAD by angiography. CONCLUSION: Regional myocardial uptake
      of FDG is enhanced even when injected 1 h post-exercise stress in a subset of
      patients with ischaemia on exercise SPECT MPI. The ability to image FDG uptake
      injected 1 h after an ischaemic episode suggests the potential utility of FDG as
      a memory marker of transient ischaemia.

PMID- 17198349
TI  - Evaluation of hepatic function with (99m)Tc-galactosylated serum albumin
      scintigraphy in patients with malaria: comparison with (99m)Tc-colloid
      scintigraphy and liver ultrasonography.
AB  - OBJECTIVE: Malarial parasites injected by the mosquito rapidly target
      hepatocytes, and hepatomegaly is commonly observed during the progress of the
      disease in malaria patients. To evaluate the degree of hepatic damage and
      functional status of hepatocytes in malaria patients, we performed liver
      scintigraphy using (99m)Tc-galactosylated serum albumin (GSA) prospectively and
      the findings were compared with those of (99m)Tc-colloid scintigraphy,
      ultrasonography and clinical results in the same subject. METHODS: Eight malaria
      patients (all male, mean age 22 years) confirmed to be infected with Plasmodium
      vivax underwent (99m)Tc-GSA liver scintigraphy, followed by liver ultrasonography
      and (99m)Tc-colloid scintigraphy using phytate within 3 days. For hepatocyte
      scintigraphy, anterior images of cardiac blood-pool and liver were continuously
      acquired for 30 min after injection of 185 MBq (99m)Tc-GSA (3 mg). In addition to
      visual interpretation of the images, quantitative measurement of hepatic function
      was performed with several functional parameters, such as hepatic uptake index
      (LHL15), blood clearance index (HH15) and modified receptor index (LHL/HH)
      calculated from the radioactivity of the liver and heart. (99m)Tc-colloid images
      were assessed and graded visually. Severity of hepatic dysfunction or
      reticuloendothelial system activation was classified as normal, mild, moderate
      and severe on GSA or colloid images. RESULTS: Hepatomegaly was observed in five
      and splenomegaly in seven of the eight patients. Serum levels of transaminase and
      alkaline phosphatase were mildly elevated in two. Visual assessment of GSA
      scintigraphy revealed normal findings in all subjects, except for mild increases
      in size. The mean values of LHL15, HH15 and LHL/HH were 0.928+/-0.014, 0.537+/
      0.031 and 1.732+/-0.106, respectively. They were graded as normal in five, and
      near-normal to mild dysfunction in three subjects. In contrast, (99m)Tc-colloid
      scintigraphy revealed abnormal findings in all of the subjects, and graded as
      moderate in three or severe reticuloendothelial system activation in five
      subjects. Liver ultrasonographic findings were normal for all subjects except
      mild hepatomegaly. CONCLUSIONS: Malaria-induced injury of the hepatocyte is
      likely to be minimal whereas hepatomegaly is commonly seen during disease
      process. This suggests that hepatic damage in malarial infection is mainly due to
      involvement of the reticuloendothelial system. (99m)Tc-GSA scintigraphy can be
      used in differentiating hepatocellular damage from reticuloendothelial system
      involvement in patients with infectious disease showing hepatomegaly.

PMID- 17198350
TI  - Is (99m)Tc-labelled pamidronate a better agent than (99m)Tc-medronate for bone
      imaging?
AB  - OBJECTIVE: To evaluate the potential of (99m)Tc-pamidronate ((99m)Tc-APD) against
      (99m)Tc-medronate ((99m)Tc-MDP) as a new bone-seeking agent using intact bone and
      fractured femur in a rat model. METHODS: (99m)Tc-APD was prepared by the stannous
      reduction method. Scintigraphic images were obtained at 2 h and 24 h after
      intravenous injection of (99m)Tc-APD or (99m)Tc-MDP in rats, then they were
      culled to estimate activities in various organs. Bone uptake (as percent injected
      dose/gram weight) was estimated in an intact femur and in 1 week post-fracture
      model. The urinary excretion dose (as percent injected dose) was also estimated.
      RESULTS: The bone uptake of (99m)Tc-APD was significantly higher (P<0.05) than
      (99m)Tc-MDP at 2 h and 24 h post-injection studies. (99m)Tc-APD uptake was
      further increased (P<0.05) in the fracture model than the intact femur. (99m)Tc
      APD uptake in the soft tissues including liver and the kidneys was lower than
      (99m)Tc-MDP. Renal excretion was faster and the ratios of bone to blood and bone
      to soft tissues were higher with APD than MDP. APD dose was selected at 1% of
      MDP, to obviate therapeutic effect, as the former compound is 100 times more
      potent than MDP. CONCLUSIONS: Our results suggest that (99m)Tc-APD uptake by
      intact bone and fractured bone was significantly higher than (99m)Tc-MDP. The
      renal clearance of (99m)Tc-APD was faster and soft tissue uptake was lower than
      (99m)Tc-MDP. These results suggest that APD has the potential to become an
      excellent bone-imaging agent.

PMID- 17198351
TI  - Segmentation of the gallbladder: effect on bile entry and exit and its clinical
      relevance in a patient with abdominal pain.
AB  - BACKGROUND: The effects of folds or septa on gallbladder filling and emptying are
      not known. METHODS: Gallbladder filling and emptying were measured in seven
      patients with two chambers (segmental) and compared with 10 subjects with a
      single chamber (control). Percent bile flow into gallbladder, and percent
      ejection fraction from the proximal and distal segments, and entire gallbladder
      were measured with cholecystokinin. RESULTS: Bile entry into gallbladder was
      similar in both groups. In patients with segmentation, overall emptying was low
      mostly due to poor emptying of the distal segment. CONCLUSION: Segmentation of
      the gallbladder does not affect bile entry, but acting as a one-way valve, a fold
      or septum lowers emptying significantly, mostly from the distal segment.

PMID- 17198352
TI  - The significance of FDG uptake in bilateral thyroid glands.
AB  - AIM: To evaluate the significance of bilateral fluorodeoxyglucose (FDG) uptake in
      the thyroid glands. METHODS: Bilateral thyroid FDG uptake, defined as
      visualization of thyroid glands, was found in 66 (3.4%) of 1925 subjects who
      underwent our FDG PET cancer-screening program. Additionally, 16 of the 41
      patients with Graves' disease and hyperthyroidism (GD(H)) and six of the 20
      subjects with Graves' disease and euthyroidism (GD(E)), who had FDG uptake in
      thyroid glands, were enrolled in this study. RESULTS: Among the 66 subjects, 22
      were normal variant, 39 subjects had chronic thyroiditis (35 subjects presented
      with diffuse goitre and four with multinodular goitre), and five subjects had
      multinodular goitre (MNG) without chronic thyroiditis. Fourteen of 22 (63.6%) of
      the subjects with the normal variant had a visual uptake intensity less than that
      of the liver, while 30 of 39 (76.9%) of the subjects with chronic thyroiditis and
      14 of 22 (63.6%) of the subjects with Graves' disease had visual uptake intensity
      greater than or equal to liver uptake. Two of the five subjects with MNG with
      focally intense uptake were proven to have thyroid carcinoma. Bilateral loser
      uptake in thyroids associated with thymus and symmetrical skeletal muscle uptake
      were found in GD(H). The standard uptake value (SUV) (mean+/-SD) in subjects with
      chronic thyroiditis (2.76+/-1.24) were higher, while those with GD(H) (1.59+/
      0.36) were lower than that of the normal variant (1.99+/-0.63). Subjects with
      hypothyroidism (3.04+/-1.39) had higher SUV levels than those subjects with
      euthyroidism (2.44+/-1.11). In addition, patients with GD(H) had lower levels
      than those with GD(E) (2.0+/-0.38). CONCLUSION: (1) Bilateral thyroidal uptake of
      FDG can be found in normal variants and subjects with various thyroid disorders,
      showing varieties of uptake patterns. (2) Diffuse intense uptake and higher SUV
      levels are a clue to a diagnosis of chronic thyroiditis, especially for those
      with hypothyroidism. (3) Focally intense uptake suggests the possibility of a
      thyroid carcinoma. (4) Sparse uptake associated with the thymus and symmetrical
      skeletal muscle uptake and lower SUV level raise the possibility of Graves'
      disease with hyperthyroidism.

PMID- 17198353
TI  - Induction of stimulating thyrotropin receptor antibodies after radioiodine
      therapy for toxic multinodular goitre and Graves' disease measured with a novel
      bioassay.
AB  - BACKGROUND: Radioactive iodine therapy (RaI) in toxic multinodular goitre (TMNG)
      has been associated with the occurrence of Graves'-like hyperthyroidism. It has
      been postulated that pre-existing autoimmunity may contribute to this phenomenon.
      OBJECTIVE: To study whether RaI induces thyrotropin receptor stimulating
      antibodies (TSAbs) in the short term in TMNG and whether pre-existing
      autoimmunity is relevant. PATIENTS: Thirty-one patients with relapsing Graves'
      disease and 17 patients with TMNG, all eligible for RaI. METHODS: Before and 6
      weeks after RaI, sera were collected and analysed for the presence of
      thyroglobulin (Tg), thyroid peroxidase antibodies (TPO-Abs) and thyrotropin
      receptor binding antibodies (TBIIs). TSAbs were analysed with a novel high
      sensitive luciferase-based bioassay based on the JP-26-26 cell line, which
      constitutively expresses the TSH receptor. RESULTS: In Graves' disease, RaI did
      not induce or increase the levels and proportion of patients with measurable
      levels of any of the antibodies measured, despite a significant increase in Tg.
      In contrast, in TMNG, RaI induced TBIIs in three TMNG patients, which was
      accompanied by measurable TSAbs on one occasion. CONCLUSIONS: We conclude from
      the present study that induction of TBIIs and TSAbs may occur shortly after RaI
      in TMNG and that pre-existing autoimmunity may not be a requirement for the
      induction of TBIIs, as evidenced by the lack of effect of RaI on TBIIs in Graves'
      disease.

PMID- 17198354
TI  - Intraperitoneal radioimmunotherapy to treat the early phase of peritoneal
      dissemination of human colon cancer cells in a murine model.
AB  - BACKGROUND AND AIM: In patients with a high risk of peritoneal dissemination of
      colon cancer, a treatment adjuvant to surgical resection would improve their
      prognosis. We aimed to determine whether radioimmunotherapy employing
      radiolabelled monoclonal antibody would work in this situation. METHODS: A murine
      model of peritoneal dissemination was established in female Balb/c nu/nu mice by
      intraperitoneal injection of LS180 human colon cancer cells. Radioimmunotherapy
      with 7.4 MBq of a murine IgG1, anti-colorectal A7 monoclonal antibody,
      radiolabelled with (131)I by the chloramine-T method was conducted
      intraperitoneally on days 0, 3, 7 and 14 after cell inoculation, respectively.
      RESULTS: Radioimmunotherapy at any timing improved survival of mice as compared
      with those of non-treated mice and mice treated with a daily dose of 30 mg x kg(
      1) of 5-fluorouracil for 4 consecutive days. The best improvement was obtained
      when radioimmunotherapy was conducted on day 0. CONCLUSION: These results
      indicate that intraperitoneal radioimmunotherapy may effectively kill colon
      cancer cells disseminated in the peritoneal cavity before formation of tumours
      and, therefore, may work as an adjuvant treatment to prevent peritoneal
      metastasis of colon cancer.

PMID- 17198355
TI  - Single photon emission computed tomography for gastric volume assessment: a
      method with observer-defined regions of interest.
AB  - AIM: Single photon emission computed tomography (SPECT) imaging allows non
      invasive measurement of gastric volume. In previous studies, the processing of
      the SPECT data involved global threshold algorithms that do not take into account
      the non-uniform distribution of radioactivity in the gastric wall. The aim of
      this study was to develop a simple alternative method based on observer-defined
      regions of interest. METHODS: A phantom study was performed to standardize volume
      calculations from SPECT derived cross-sectional areas. In 12 healthy volunteers,
      the principle was then used to determine gastric volume before and after a 600 ml
      liquid meal. Furthermore, gastric emptying of the meal was followed with planar
      scintigraphy. RESULTS: The median volume of the stomach was 86 ml (range 62-130
      ml) at baseline, 642 ml (536-748 ml) immediately after the meal, and 370 ml (221
      481 ml) 1 h after the meal. The coefficient of variation for the calculations was
      9%, 2% and 4%, respectively. The median increase in gastric volume was 562 ml
      (501-628 ml) immediately after the meal and 294 ml (159-370 ml) after 1 h.
      Gastric retention of the meal was 68% (50-73%) after 0.5 h and 51% (39-57%) after
      1 h. CONCLUSIONS: The present manual technique may be a reliable alternative to
      the automated SPECT methods for assessing gastric volume. The liquid meal that
      was used in our study did not seem to cause an increase in gastric volume that
      differed from the volume of the meal.

PMID- 17198356
TI  - Fixation devices for whole-body 18F-FDG PET/CT: patient perspectives and
      technical aspects.
AB  - OBJECTIVE: To evaluate the use of a fixation device in whole-body postiron
      emission tomography/computed tomography (PET/CT). METHODS: Two hundred and thirty
      patients were prospectively included over a period of 3 months. Different single
      phase and multiphase contrast-enhanced PET/CT protocols were used for whole-body
      examination. An unforced expiration state was applied as breathing protocol for
      CT examination. Patients were placed on a deflating device (1.0 m x 1.5 m) with
      arms elevated but supported in order to prevent full extension in shoulders and
      elbows providing comfortable positioning. Image quality was assessed by means of
      alignment of the liver quantitatively on co-registered PET/CT images. After the
      examination, patients were asked to complete a survey on subjective sensations
      such as pain in different body regions (yes/no). They were asked to give a final
      evaluation for the whole-body PET/CT examination (comfortable/not comfortable).
      Additionally, a control group (n=30) was assessed without the aid of additional
      devices. RESULTS: Examination protocols using the device showed minor
      misalignment of 5 mm. Different protocols did not reveal significant differences
      in misalignment. When comparing the control group misalignment was significantly
      higher with approx. 7 mm. The majority (75%) evaluated the positioning as
      comfortable despite 46% of the patients in this group feeling more or less severe
      pain in at least one body region. For controls, misalignment was slightly higher
      whereas only 39% found the positioning comfortable (chi(2)=13.03; P<0.0005) and
      61% reported pain (NS). CONCLUSION: Both the technical aspects and patient
      evaluations favour the use of the vacuum device in whole-body PET/CT
      examinations. In particular, in time consuming protocols using multiphase CT
      examination the fixation device leads to excellent co-registration quality and
      patient compliance.

PMID- 17198371
TI  - Relationship between the size of the bottleneck 15 A from iron in the main
      channel and the reactivity of catalase corresponding to the molecular size of
      substrates.
AB  - A catalase that exhibits a high level of activity and a rapid reaction with
      organic peroxides has been purified from Exiguobacterium oxidotolerans T-2-2T
      (EKTA catalase). The amino acid sequence of EKTA catalase revealed that it is a
      novel clade 1 catalase. Amino acid residues in the active site around the
      protoheme are conserved in the primary structure of EKTA catalase. Although the
      general interactions of molecules larger than hydrogen peroxide with catalases
      are strongly inhibited because of the selection role of long and narrow channels
      in the substrate reaching the active site, the formation rate of reactive
      intermediates (compound I) in the reaction of EKTA catalase with peracetic acid
      is 77 times higher than that of bovine liver catalase (BLC) and 1200 times higher
      than that of Micrococcus luteus catalase (MLC). The crystal structure of EKTA
      catalase has been determined and refined to 2.4 A resolution. The main channel
      structure of EKTA catalase is different from those of BLC and MLC. The rate
      constant of compound I formation in catalases decreased with an increase in the
      molecular size of the substrate. For EKTA catalase with a larger bottleneck 15 A
      from the iron (entrance of narrow channel) in the main channel, a lower rate of
      reduction in compound I formation rate with an increase in the molecular size of
      substrates was found. The increase in the rate constant of compound I formation
      in these catalases was directly proportional to the increase in the size of the
      bottleneck in the main channel when molecules of substrates larger than H2O2,
      such as organic peroxides, are used in the reaction. The results indicate that
      the size of the bottleneck in the main channel in catalase is an important factor
      in defining the rate of compound I formation corresponding to the molecular size
      of the substrates, and this was demonstrated. The Leu149-Ile180 and Asp109-Met167
      combinations at the entrance of the narrow channel in EKTA catalase determine the
      size of the bottleneck, and each atom-to-atom distance for the combination of
      residues was larger than those of corresponding combinations of amino acid
      residues in BLC and MLC. The combination of these four amino acids is quite
      specific in EKTA catalase as compared with the combinations in other catalases in
      the gene database (compared with more than 432 catalase genes in the database).

PMID- 17198372
TI  - Low-affinity signature of the rat beta-parvalbumin CD site. Evidence for remote
      determinants.
AB  - Although rat beta-parvalbumin and chicken parvalbumin 3 (CPV3) are identical at
      74 of 108 residues, rat beta exhibits perceptibly lower Ca2+ and Mg2+ affinities.
      At 25 degrees C, in Hepes-buffered saline, at pH 7.4, the overall deltadeltaG
      degrees ' values are 2.0 and 3.9 kcal/mol, respectively. These differences
      primarily reflect the disparate behavior of the CD sites in the two proteins.
      Their respective binding constants for Ca2+, for example, are 1.5 x 10(6) and 2.4
      x 10(7) M-1. The extent to which this differential behavior is dictated by local
      and remote sequence differences is unknown. To explore this question, we
      performed mutagenesis on rat beta, substituting the corresponding CPV3 codon for
      residues 49, 50, 57, 58, 59, and 60. The resulting CD site is identical to CPV3
      at 27 of 30 positions. The mutations were introduced in four stages, replacing
      residues 49 and 50 (yielding beta 49/50), then 57 and 58 (beta 49/50/57/58), then
      59 (beta 49/50/57/58/59), and finally 60 (beta 49/50/57/58/59/60). Apoprotein
      stability was examined by scanning calorimetry and chemical denaturation and
      divalent ion affinity by titration calorimetry. All four variants exhibit
      elevated Tm values and are between 0.13 and 0.39 kcal/mol more stable at 25
      degrees C. Although all four proteins display heightened divalent ion affinity,
      the increases are small. The maximal deltadeltaG degrees ' values, observed for
      49/50/57/58/59/60, are just -0.56 and -0.96 kcal/mol for Ca2+ and Mg2+,
      respectively. Evidently, structural features beyond the metal ion-binding motif
      contribute to the unusual divalent ion-binding behavior associated with the rat
      beta CD site.

PMID- 17198370
TI  - Plasticity of amyloid fibrils.
AB  - In experiments designed to characterize the basis of amyloid fibril stability
      through mutational analysis of the Abeta (1-40) molecule, fibrils exhibit
      consistent, significant structural malleability. In these results, and in other
      properties, amyloid fibrils appear to more resemble plastic materials generated
      from synthetic polymers than globular proteins. Thus, like synthetic polymers and
      plastics, amyloid fibrils exhibit both polymorphism, the ability of one
      polypeptide to form aggregates of different morphologies, and isomorphism, the
      ability of different polypeptides to grow into a fibrillar amyloid morphology.
      This view links amyloid with the prehistorical and 20th century use of proteins
      as starting materials to make films, fibers, and plastics, and with the classic
      protein fiber stretching experiments of the Astbury group. Viewing amyloids from
      the point of view of the polymer chemist may shed new light on a number of
      issues, such as the role of protofibrils in the mechanism of amyloid formation,
      the biological potency of fibrils, and the prospects for discovering inhibitors
      of amyloid fibril formation.

PMID- 17198373
TI  - Recognition characteristics of monoclonal antibodies that are cross-reactive with
      gangliosides and lipooligosaccharide from Campylobacter jejuni strains associated
      with Guillain-Barre and Fisher syndromes.
AB  - The enteropathogen Campylobacter jejuni has the ability to synthesize glycan
      structures that are similar to mammalian gangliosides within the core component
      of its lipooligosaccharide (LOS). Exposure to ganglioside mimics in some
      individuals results in the production of autoantibodies that deleteriously attack
      nerve surface gangliosides, precipitating the onset of Guillain-Barre and Fisher
      syndromes (GBS and FS). We have characterized the interaction of four monoclonal
      antibodies (mAbs), established by sensitization of mice with LOS isolated from
      GBS- and FS-associated C. jejuni strains, with chemoenzymatically synthesized
      gangliooligosaccharides. Surface plasmon resonance (SPR) measurements demonstrate
      that three of the mAbs interact specifically with derivatives corresponding to
      their targeted gangliosides, with dissociation constants ranging from 10 to 20
      microM. Antibody binding to the gangliooligosaccharides was probed by saturation
      transfer difference (STD) NMR spectroscopy. STD signals, resulting from
      antibody/oligosaccharide interaction, were observed for each of the four mAbs. In
      two cases, differential saturation transfer rates to oligosaccharide resonances
      enabled detailed epitope mapping. The binding of GD1a-S-Phe with GB1 is
      characterized by close association of the immunoglobulin with sites that are
      distributed over several residues of the oligosaccharide. This contrasts sharply
      with the profile observed for the binding of both GD3-S-Phe and GT1a-S-Phe with
      FS1. The close antigenic contacts in these ganglioside derivatives are confined
      to the N-acetylmannosaminyl portion of the terminal N-acetylneuraminic acid
      (NeuAc) residue of the disialosyl moiety. Our characterization of FS1 provides
      insight, at an atomic level, into how a single antigenic determinant presented by
      the LOS of C. jejuni can give rise to antibodies with binding promiscuity to
      [alphaNeuAc-(2-8)-alphaNeuAc]-bound epitopes and demonstrates why sera from FS
      patients have antibodies that are often reactive with more than one disialylated
      ganglioside.

PMID- 17198374
TI  - The alpha helix of ubiquitin interacts with yeast cyclin-dependent kinase subunit
      CKS1.
AB  - Ubiquitin serves as a molecular zipcode to direct and sort ubiquitinylated
      proteins into distinct biological pathways. Although novel modes of ubiquitin
      interaction have recently been characterized, conventional ubiquitin-binding
      domains (UBDs) recognize ubiquitin through a hydrophobic pocket centered around
      isoleucine 44 and lined by residues in beta sheets 3 and 4. In this study, we
      report a novel mode of interaction between ubiquitin and the cyclin-dependent
      kinase subunit of Saccharomyces cerevisiae, Cks1p, an adaptor protein involved in
      transcriptional regulation through recruitment of proteasomal subunits to gene
      promoters. Cks1p interacts specifically with monoubiquitin and tetraubiquitin
      with an affinity several orders of magnitude greater than that of other ubiquitin
      binding domains and in an unconventional fashion, which differs from interactions
      documented so far between ubiquitin and conventional UBDs. The loop between
      helices alpha 1 and alpha 2, and to a minor extent the N-terminal alpha-helix of
      Cks1p, are involved in the interaction with the alpha-helix of ubiquitin, instead
      of its I44-centered hydrophobic pocket. Not only is this the first time the alpha
      helix of ubiquitin is implicated in a protein/protein interaction, thereby
      shedding new light on the mechanisms of ubiquitin recognition, but also the first
      report of a direct physical interaction between ubiquitin and Cks1p, inferring a
      role for ubiquitin binding in the transcriptional function of Cks1p.

PMID- 17198375
TI  - Mechanism of interaction of the double-stranded RNA (dsRNA) binding domain of
      protein kinase R with short dsRNA sequences.
AB  - The dsRNA-activated protein kinase (PKR) plays a major role in the cellular
      response to viral infection. PKR contains an N-terminal dsRNA binding domain
      (dsRBD) and a C-terminal kinase domain. The dsRBD consists of two tandem copies
      of a conserved double-stranded RNA binding motif, dsRBM1 and dsRBM2. dsRNA
      binding is believed to activate PKR by inducing dimerization and subsequent
      autophosphorylation reactions. We have characterized the function of the dsRBD by
      assessing the binding of dsRBM1 and dsRBD to a series of dsRNA sequences ranging
      from 15 to 45 bp. For dsRBM1, the binding stoichiometries agree with an
      overlapping ligand binding model where the motif binds to multiple faces of the
      dsRNA duplex and overlaps along the helical axis. Similar behavior is observed
      for a dsRBD containing both dsRBM1 and dsRBM2 for sequences up to 30 bp; however,
      the binding affinity is enhanced 30-fold. Longer dsRNA sequences exhibit lower
      than-expected stoichiometries, indicating a change in binding mode. NMR
      spectroscopy was used to define the regions of the dsRBD that interact with
      dsRNA. dsRNA binding induces exchange broadening of cross-peaks in 1H-15N HSQC
      spectra. For a 20 bp dsRNA, the resonances most affected map to the known dsRNA
      binding regions of dsRBM1 as well as the N-terminus of dsRBM2. For a longer 40 bp
      sequence, additional regions of dsRBM2 exhibit enhanced broadening. These data
      support a model in which dsRBM1 plays the dominant role in binding short dsRNA
      sequences and dsRBM2 makes additional interactions with the longer sequences
      capable of activating PKR.

PMID- 17198376
TI  - Manganese oxidation site in Pleurotus eryngii versatile peroxidase: a site
      directed mutagenesis, kinetic, and crystallographic study.
AB  - The molecular architecture of versatile peroxidase (VP) includes an exposed
      tryptophan responsible for aromatic substrate oxidation and a putative Mn2+
      oxidation site. The crystal structures (solved up to 1.3 A) of wild-type and
      recombinant Pleurotus eryngii VP, before and after exposure to Mn2+, showed a
      variable orientation of the Glu36 and Glu40 side chains that, together with
      Asp175, contribute to Mn2+ coordination. To evaluate the involvement of these
      residues, site-directed mutagenesis was performed. The E36A, E40A, and D175A
      mutations caused a 60-85-fold decrease in Mn2+ affinity and a decrease in the
      Mn2+ oxidation activity. Transient-state kinetic constants showed that reduction
      of both compounds I and II was affected (80-325-fold lower k2app and 103-104-fold
      lower k3app, respectively). The single mutants retained partial Mn2+ oxidation
      activity, and a triple mutation (E36A/E40A/D175A) was required to completely
      suppress the activity (<1% kcat). The affinity for Mn2+ also decreased (
      approximately 25-fold) with the shorter carboxylate side chain in the E36D and
      E40D variants, which nevertheless retained 30-50% of the maximal activity,
      whereas similar mutations caused a 50-100-fold decrease in kcat in the case of
      the Phanerochaete chrysosporium manganese peroxidase (MnP). Additional mutations
      showed that introduction of a basic residue near Asp175 did not improve Mn2+
      oxidation as found for MnP and ruled out an involvement of the C-terminal tail of
      the protein in low-efficiency oxidation of Mn2+. The structural and kinetic data
      obtained highlighted significant differences in the Mn2+ oxidation site of the
      new versatile enzyme compared to P. chrysosporium MnP.

PMID- 17198378
TI  - Amino acid residues His183 and Glu264 in Bacillus subtilis ferrochelatase direct
      and facilitate the insertion of metal ion into protoporphyrin IX.
AB  - Ferrochelatase catalyzes the terminal step in the heme biosynthetic pathway,
      i.e., the incorporation of Fe(II) into protoporphyrin IX. Various biochemical and
      biophysical methods have been used to probe the enzyme for metal binding residues
      and the location of the active site. However, the location of the metal binding
      site and the path of the metal into the porphyrin are still disputed. Using site
      directed mutagenesis on Bacillus subtilis ferrochelatase we demonstrate that
      exchange of the conserved residues His183 and Glu264 affects the metal affinity
      of the enzyme. We also present the first X-ray crystal structure of
      ferrochelatase with iron. Only a single iron was found in the active site,
      coordinated in a square pyramidal fashion by two amino acid residues, His183 and
      Glu264, and three water molecules. This iron was not present in the structure of
      a His183Ala modified ferrochelatase. The results strongly suggest that the
      insertion of a metal ion into protoporphyrin IX by ferrochelatase occurs from a
      metal binding site represented by His183 and Glu264.

PMID- 17198377
TI  - Mutational analysis of Escherichia coli MoeA: two functional activities map to
      the active site cleft.
AB  - The molybdenum cofactor is ubiquitous in nature, and the pathway for Moco
      biosynthesis is conserved in all three domains of life. Recent work has helped to
      illuminate one of the most enigmatic steps in Moco biosynthesis, ligation of
      metal to molybdopterin (the organic component of the cofactor) to form the active
      cofactor. In Escherichia coli, the MoeA protein mediates ligation of Mo to
      molybdopterin while the MogA protein enhances this process in an ATP-dependent
      manner. The X-ray crystal structures for both proteins have been previously
      described as well as two essential MogA residues, Asp49 and Asp82. Here we
      describe a detailed mutational analysis of the MoeA protein. Variants of
      conserved residues at the putative active site of MoeA were analyzed for a loss
      of function in two different, previously described assays, one employing moeA-
      crude extracts and the other utilizing a defined system. Oddly, no correlation
      was observed between the activity in the two assays. In fact, our results showed
      a general trend toward an inverse relationship between the activity in each
      assay. Moco binding studies indicated a strong correlation between a variant's
      ability to bind Moco and its activity in the purified component assay. Crystal
      structures of the functionally characterized MoeA variants revealed no major
      structural changes, indicating that the functional differences observed are not
      due to disruption of the protein structure. On the basis of these results, two
      different functional areas were assigned to regions at or near the MoeA active
      site cleft.

PMID- 17198379
TI  - Structural role of tyrosine 98 in photoactive yellow protein: effects on
      fluorescence, gateway, and photocycle recovery.
AB  - We have recently shown that the Y98Q mutant of PYP has a major effect on the
      photocycle kinetics ( approximately 40 times slower recovery). We have now
      determined the crystal structure of Y98Q at 2.2 A resolution to reveal the role
      of residue Y98 in the PYP photocycle. Although the overall structure is very
      similar to that of WT, we observed two major effects of the mutation. One obvious
      consequence is a conformational change of the beta4-beta5 loop, which includes a
      repositioning of residue M100. It had previously been shown that the photocycle
      is slowed by as much as 3 orders of magnitude when residue M100 is substituted or
      when the conformation is altered as in Rhodocista centenaria PYP. To investigate
      whether the altered photocycle of Y98Q is due to this repositioning of M100 or is
      caused by an effect unrelated to M100, we determined the dark recovery kinetics
      of the Y98Q/M100A mutant. We find the recovery kinetics to be very similar to the
      M100A single mutant kinetics and therefore conclude that the slower recovery
      kinetics in Y98Q are most likely due to repositioning of M100. In addition, we
      find that other substitutions at position 98 (Y98W, Y98L, and Y98A) have
      differing effects on the photocycle recovery, presumably due to a variable
      distortion of the beta4-beta5 loop. The second effect of the Y98Q mutation is a
      repositioning of R52, which is thought to interact with Y98 in WT PYP and now
      forms new interactions with residues Q99 and Q56. To determine the role of R52,
      we also characterized an R52A/M100A double mutant and found that the effects on
      the recovery kinetics ( approximately 2000 slower recovery than WT) are due to
      unrelated events in the photocycle. Since the Y98Q/M100A recovery kinetics are
      more similar to those of M100 than R52A/M100A, we conclude that the repositioning
      of R52, caused by the Y98Q mutation, does not affect the dark state recovery. In
      addition, it has been proposed that Y98 and P68 are "gateway residues" between
      which the chromophore must pass during isomerization. We tested the recovery
      kinetics of mutant P68A and found that, although the gateway may be important for
      photocycle initiation, its role in recovery to the ground state is minimal.

PMID- 17198381
TI  - Mutational analysis of peptidoglycan amidase MepA.
AB  - Murein endopeptidase A (MepA) from Escherichia coli is a periplasmic
      peptidoglycan amidase that cleaves d,d amide bonds between d-alanine and meso-2,6
      diaminopimelic acid in E. coli peptidoglycan. MepA and its homologues in other
      proteobacteria share overall structural similarity with d-Ala-d-Ala
      metallopeptidases and local similarity around the active site with lysostaphin
      type enzymes, which has prompted the classification of these enzymes as LAS
      enzymes. LAS enzymes contain a single divalent cation in the active site, which
      is tetracoordinated in the crystal structures. Three of the metal ligands are
      identical in all structures, but the identity of the fourth ligand varies. Two
      residues in proximity to the metal might act as a general acid/base, but their
      role is not clear. Here, we report a new MepA expression system, which allows the
      separation of MepA variants from the endogenous wild-type enzyme, and an HPLC
      assay with a defined peptidoglycan fragment, which allows assessment of MepA
      activity without a refolding step. We find that the conserved metal ligands are
      required for folding (D120) or catalysis (H113, H211). Separate mutations of the
      candidate catalytic residues H206 or H209 and of the "fourth" metal ligand H110
      are tolerated for folding but drastically reduce activity. Mutation of residue
      W203 to aspartate impairs substrate binding.

PMID- 17198380
TI  - Mechanism of interactions of alpha-naphthoflavone with cytochrome P450 3A4
      explored with an engineered enzyme bearing a fluorescent probe.
AB  - Design of a partially cysteine-depleted C98S/C239S/C377S/C468A cytochrome P450
      3A4 mutant designated CYP3A4(C58,C64) allowed site-directed incorporation of
      thiol-reactive fluorescent probes into alpha-helix A. The site of modification
      was identified as Cys-64 with the help of CYP3A4(C58) and CYP3A4(C64), each
      bearing only one accessible cysteine. Changes in the fluorescence of
      CYP3A4(C58,C64) labeled with 6-(bromoacetyl)-2-(dimethylamino)naphthalene
      (BADAN), 7-(diethylamino)-3-(4'-maleimidylphenyl)-4-methylcoumarin (CPM), or
      monobromobimane (mBBr) were used to study the interactions with bromocriptine
      (BCT), 1-pyrenebutanol (1-PB), testosterone (TST), and alpha-naphthoflavone
      (ANF). Of these substrates only ANF has a specific effect, causing a considerable
      decrease in fluorescence intensity of BADAN and CPM and increasing the
      fluorescence of mBBr. This ANF-binding event in the case of the BADAN-modified
      enzyme is characterized by an S50 of 18.2 +/- 0.7, compared with the value of 2.2
      +/- 0.3 for the ANF-induced spin transition, thus revealing an additional low
      affinity binding site. Studies of the effect of TST, 1-PB, and BCT on the
      interactions of ANF monitored by changes in fluorescence of CYP3A4(C58,C64)-BADAN
      or by the ANF-induced spin transition revealed no competition by these
      substrates. Investigation of the kinetics of fluorescence increase upon H2O2
      dependent heme depletion suggests that labeled CYP3A4(C58,C64) is represented by
      two conformers, one of which has the fluorescence of the BADAN and CPM labels
      completely quenched, presumably by photoinduced electron transfer from the
      neighboring Trp-72 and/or Tyr-68 residues. The binding of ANF to the newly
      discovered binding site appears to affect the interactions of the label with the
      above residue(s), thus modulating the fraction of the fluorescent conformer.

PMID- 17198382
TI  - Acyl carrier protein phosphodiesterase (AcpH) of Escherichia coli is a non
      canonical member of the HD phosphatase/phosphodiesterase family.
AB  - The Escherichia coli AcpH acyl carrier protein phosphodiesterase (also called ACP
      hydrolyase) is the only enzyme known to cleave a phosphodiester-linked post
      translational protein modification. AcpH hydrolyzes the link between 4'
      phosphopanthetheine and the serine-36 side chain of acyl carrier protein (ACP).
      Although the existence of this enzyme activity has long been known, study of the
      enzyme was hampered by its recalcitrant properties and scarcity. We recently
      isolated the gene encoding AcpH and have produced the recombinant enzyme in
      quantity (Thomas, J., and Cronan, J. E., (2005) J. Biol. Chem. 280, 34675-34683),
      thus allowing the first studies of its reaction mechanism. AcpH requires Mn2+ for
      activity, and thus, we focused on the metal binding ligands in order to locate
      the active site. Bioinformatic investigations indicated that AcpH and its
      homologues were weakly related to a phosphodiesterase of known structure, the
      hydrolyase domain of the bifunctional bacterial protein, SpoT, suggesting that
      AcpH is a member of the HD family of phosphatases/ phosphodiesterases despite
      lacking the characteristic histidine of the motif. Indeed, we found that AcpH
      could be convincingly modeled on the SpoT structure with acceptable parameters,
      which allowed the identification of putative metal binding ligands. These were
      then tested by site-directed mutagenesis. Mutagenic removal of any of the
      putative ligands resulted in a severe or total loss of phosphodiesterase
      activity. In two cases, the H6Q and D24N proteins, the residual activities could
      be markedly stimulated by addition of high Mn2+ concentrations, thereby
      demonstrating a role for these residues in metal binding. We conclude that AcpH
      is a member of the HD protein family despite the lack of the signature histidine
      residue.

PMID- 17198383
TI  - Structural characterization of a beta-diketone hydrolase from the cyanobacterium
      Anabaena sp. PCC 7120 in native and product-bound forms, a coenzyme A-independent
      member of the crotonase suprafamily.
AB  - The gene alr4455 from the well-studied cyanobacterium Anabaena sp. PCC 7120
      encodes a crotonase orthologue that displays beta-diketone hydrolase activity.
      Anabaena beta-diketone hydrolase (ABDH), in common with 6-oxocamphor hydrolase
      (OCH) from Rhodococcus sp. NCIMB 9784, catalyzes the desymmetrization of
      bicyclo[2.2.2]octane-2,6-dione to yield [(S)-3-oxocyclohexyl]acetic acid, a
      reaction unusual among the crotonase superfamily as the substrate is not an acyl
      CoA thioester. The structure of ABDH has been determined to a resolution of 1.5 A
      in both native and ligand-bound forms. ABDH forms a hexamer similar to OCH and
      features one active site per enzyme monomer. The arrangement of side chains in
      the active site indicates that while the catalytic chemistry may be conserved in
      OCH orthologues, the structural determinants of substrate specificity are
      different. In the active site of ligand-bound forms that had been cocrystallized
      with the bicyclic diketone substrate bicyclo[2.2.2]octane-2,6-dione was found the
      product of the asymmetric enzymatic retro-Claisen reaction [(S)-3
      oxocyclohexyl]acetic acid. The structures of ABDH in both native and ligand-bound
      forms reveal further details about structural variation and modes of coenzyme A
      independent activity within the crotonases and provide further evidence of a
      wider suprafamily of enzymes that have recruited the crotonase fold for the
      catalysis of reactions other than those regularly attributed to canonical
      superfamily members.

PMID- 17198384
TI  - Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme enzyme
      involved in tryptophan catabolism and in quinolinate biosynthesis.
AB  - The structure of tryptophan 2,3-dioxygenase (TDO) from Ralstonia metallidurans
      was determined at 2.4 A. TDO catalyzes the irreversible oxidation of l-tryptophan
      to N-formyl kynurenine, which is the initial step in tryptophan catabolism. TDO
      is a heme-containing enzyme and is highly specific for its substrate l
      tryptophan. The structure is a tetramer with a heme cofactor bound at each active
      site. The monomeric fold, as well as the heme binding site, is similar to that of
      the large domain of indoleamine 2,3-dioxygenase, an enzyme that catalyzes the
      same reaction except with a broader substrate tolerance. Modeling of the putative
      (S)-tryptophan hydroperoxide intermediate into the active site, as well as
      substrate analogue and mutagenesis studies, are consistent with a Criegee
      mechanism for the reaction.

PMID- 17198386
TI  - Self-assembly of double-stranded DNA molecules at nanomolar concentrations.
AB  - Some proteins have the property of self-assembly, known to be an important
      mechanism in constructing supramolecular architectures for cellular functions.
      However, as yet, the ability of double-stranded (ds) DNA molecules to self
      assemble has not been established. Here we report that dsDNA molecules also have
      a property of self-assembly in aqueous solutions containing physiological
      concentrations of Mg2+. We show that DNA molecules preferentially interact with
      molecules with an identical sequence and length even in a solution composed of
      heterogeneous DNA species. Curved DNA and DNA with an unusual conformation and
      property also exhibit this phenomenon, indicating that it is not specific to
      usual B-form DNA. Atomic force microscopy (AFM) directly reveals the assembled
      DNA molecules formed at concentrations of 10 nM but rarely at 1 nM. The self
      assembly is concentration-dependent. We suggest that the attractive force causing
      DNA self-assembly may function in biological processes such as folding of
      repetitive DNA, recombination between homologous sequences, and synapsis in
      meiosis.

PMID- 17198385
TI  - Human glycinamide ribonucleotide transformylase: active site mutants as
      mechanistic probes.
AB  - Human glycinamide ribonucleotide transformylase (GART) (EC 2.1.2.2) is a
      validated target for cancer chemotherapy, but mechanistic studies of this
      therapeutically important enzyme are limited. Site-directed mutagenesis, initial
      velocity studies, pH-rate studies, and substrate binding studies have been
      employed to probe the role of the strictly conserved active site residues, N106,
      H108, and D144, and the semiconserved K170 in substrate binding and catalysis.
      Only two conservative substitutions, N106Q and K170R, resulted in catalytically
      active enzymes, and these active mutant enzymes gave pH-rate profiles and a
      steady-state kinetic mechanism essentially identical to those of the native
      enzyme. All inactive mutants were able to bind both substrates, ruling out
      disrupted formation of the ternary complex as the source of inactivity.
      Differences between human and Escherichia coli GART, previously used as a model
      for the human enzyme, were evident.

PMID- 17198387
TI  - Folding cooperativity in RNA and DNA is dependent on position in the helix.
AB  - Secondary structural motifs play essential roles in the folding and function of
      RNA and DNA molecules. Previous work from our lab compared the folding of small
      DNA and RNA hairpin loops containing a sheared GA pair [Moody, E. M., Feerar, J.
      C., and Bevilacqua, P. C. (2004) Biochemistry 43, 7992-7998]. We found that the
      small DNA hairpins fold in a highly cooperative manner with indirect coupling,
      while their RNA counterparts fold in a much less cooperative fashion and display
      direct coupling. Herein, we extend this study to the double-stranded helix. We
      carried out double mutant cycles on base pairs having identical nearest-neighbor
      contexts but located in either external or internal helical registers. In the
      external register, both RNA and DNA exhibit extensive folding cooperativity
      between the penultimate and terminal base pair, which is independent of mismatch
      identity. In contrast, DNA exhibits virtually no folding cooperativity in the
      center of the helix, while RNA maintains substantial coupling, which is dependent
      on mismatch identity. Two models account for these non-nearest-neighbor effects:
      one involves the unfavorable entropy of helix initiation common to DNA and RNA,
      and the other involves steric and electrostatic strain peculiar to RNA. These
      data show that RNA can display cooperativity less than, greater than, or equal to
      that of DNA depending on context and position.

PMID- 17198388
TI  - 4-hydroxyequilenin-adenine lesions in DNA duplexes: stereochemistry, damage site,
      and structure.
AB  - The equine estrogens, equilin and equilenin, are major components of the drug
      Premarin, the most widely used formula for hormone replacement therapy. The
      derivative 4-hydroxyequilenin (4-OHEN), a major phase I metabolite of equilin and
      equilenin, autoxidizes to potent cytotoxic quinoids that can react in vitro and
      in vivo with cytosine and adenine in DNA. Unique cyclic adducts containing the
      same bicyclo[3.3.1]nonane-type connection ring are produced. Each base adduct has
      four stereoisomers. In order to elucidate the structural effects of A versus C
      modification, we have carried out molecular dynamics simulations of the
      stereoisomeric 4-OHEN-A adducts in DNA 11-mer duplexes and compared results with
      an earlier study of the C adducts (Ding, S., Shapiro, R., Geacintov, N.E., and
      Broyde, S. (2005) Equilenin-Derived DNA Adducts to Cytosine in DNA Duplexes:
      Structures and Thermodynamics, Biochemistry 44, 14565-14576). Similar
      stereochemical principles govern the orientations in DNA duplexes of the 4-OHEN-A
      adducts as for the analogous C adducts, with opposite orientations of the
      equilenin rings in stereoisomeric pairs of adducts characterized by near-mirror
      image circular dichroism (CD) spectra. However, the larger purine adducts have
      unique structural properties in the duplexes that distinguish their
      characteristics from those of the pyrimidine adducts. Significant differences are
      observed in terms of hydrogen bonding, stacking, bending, groove dimensions,
      solvent exposure, and hydrophobic interactions; also, each of the four
      stereoisomeric 4-OHEN-A adducts exhibit distinct structural features. Each base
      adduct and stereoisomer distorts the structure of the DNA duplex differently.
      These characteristics may manifest themselves in terms of differential nucleotide
      excision repair susceptibilities and mutagenic activities of the 4-OHEN-A and C
      adducts.

PMID- 17198389
TI  - Unmasking Anticooperative DNA-binding interactions of vaccinia DNA topoisomerase
      I.
AB  - Vaccinia DNA topoisomerase (vTopo) catalyzes highly specific nucleophilic
      substitution at a single phosphodiester linkage in the pentapyrimidine
      recognition sequence 5'-(C/T)+5C4+C3+T+2T+1p ?N-1 using an active-site tyrosine
      nucleophile, thereby expelling a 5' hydroxyl leaving group of the DNA. Here, we
      report the energetic effects of subtle modifications to the major-groove hydrogen
      bond donor and acceptor groups of the 3'-GGGAA-5' consensus sequence of the
      nonscissile strand in the context of duplexes in which the scissile strand length
      was progressively shortened. We find that the major-groove substitutions become
      energetically more damaging as the scissile strand is shortened from 32 to 24 and
      18 nucleotides, indicating that enzyme interactions with the duplex region
      present in the 32-mer but not the 24- or 18-mer weaken specific interactions with
      the DNA major groove. Regardless of strand length, the destabilizing effects of
      the major-groove substitutions increase as the reaction proceeds from the
      Michaelis complex to the transition state for DNA cleavage and, finally, to the
      phosphotyrosine-DNA covalent complex. These length-dependent anticooperative
      interactions involving the DNA major groove and duplex regions 3' to the cleavage
      site indicate that the major-groove binding energy is fully realized late during
      the reaction for full-length substrates but that smaller more flexible duplex
      substrates feel these interactions earlier along the reaction coordinate. Such
      anticooperative binding interactions may play a role in strand exchange and
      supercoil unwinding activities of the enzyme.

PMID- 17198390
TI  - Energetics of codon-anticodon recognition on the small ribosomal subunit.
AB  - Recent crystal structures of the small ribosomal subunit have made it possible to
      examine the detailed energetics of codon recognition on the ribosome by
      computational methods. The binding of cognate and near-cognate anticodon stem
      loops to the ribosome decoding center, with mRNA containing the Phe UUU and UUC
      codons, are analyzed here using explicit solvent molecular dynamics simulations
      together with the linear interaction energy (LIE) method. The calculated binding
      free energies are in excellent agreement with experimental binding constants and
      reproduce the relative effects of mismatches in the first and second codon
      position versus a mismatch at the wobble position. The simulations further
      predict that the Leu2 anticodon stem loop is about 10 times more stable than the
      Ser stem loop in complex with the Phe UUU codon. It is also found that the
      ribosome significantly enhances the intrinsic stability differences of codon
      anticodon complexes in aqueous solution. Structural analysis of the simulations
      confirms the previously suggested importance of the universally conserved
      nucleotides A1492, A1493, and G530 in the decoding process.

PMID- 17198391
TI  - The S1YZ* metalloradical EPR signal of photosystem II contains two distinct
      components that advance respectively to the multiline and g = 4.1 conformations
      of S2.
AB  - The S2 state of the oxygen-evolving complex (OEC) of photosystem II is
      heterogeneous, exhibiting two main EPR spectral forms, the multiline and the g =
      4.1 signal. It is not clearly established whether this heterogeneity develops
      during the S1 to S2 transition or is already present in the precursor states. We
      have compared the spectra of the S1YZ* intermediate, obtained by visible light
      excitation (induction of charge separation) of the S1 state at liquid He
      temperatures, (S1YZ*)vis, or by near-infrared (NIR) light excitation of the S2
      state (utilization of the unusual property of the Mn cluster to act as an oxidant
      of Yz when excited by NIR), (S1YZ*)NIR. The decay kinetics of the (S1YZ*)vis
      spectrum at 11 K was also studied by the application of rapid-scan EPR. The two
      spectra share in common a signal with a characteristic feature at g = 2.035, but
      the (S1YZ*)vis spectrum contains in addition a fast decaying component 26 G wide.
      The analysis of the surface of the rapid-scan spectra yielded 270 +/- 35 and 90
      +/- 15 s for the respective half-times of the two components of the (S1YZ*)vis
      spectrum at 11 K. (S1YZ*)vis advances efficiently to S2 when annealed at 200 K;
      notably the g = 2.035 signal advances to the multiline while the 26 G component
      advances to the g = 4.1 conformation. The "26 G" component is absent or very
      small, respectively, in thermophilic cyanobacteria or glycerol-containing spinach
      samples, in correlation to vanishing or very small amounts of the g = 4.1
      component in the S2 spectrum. The results validate the assignment of S1YZ* to a
      true S1 to S2 intermediate and imply that the heterogeneity observed in S2 is
      already present in S1. Tentative valences are assigned to the individual Mn ions
      of the OEC in the two heterogeneous conformations of S1.

PMID- 17198392
TI  - The sequence determinant causing different folding behaviors of insulin and
      insulin-like growth factor-1.
AB  - Although insulin and insulin-like growth factor-1 (IGF-1) belong to the insulin
      superfamily and share highly homologous sequences, similar tertiary structure,
      and a common ancestor molecule, amphioxus insulin-like peptide, they have
      different folding behaviors: IGF-1 folds into two thermodynamically stable
      tertiary structures (native and swap forms), while insulin folds into one unique
      stable structure. To further understand which part of the sequence determines
      their different folding behavior, based on previous reports from the laboratory,
      two peptide models, [B9A][1-4]porcine insulin precursor (PIP) and [B10E][1-4]PIP,
      were constructed. The plasmids encoding the peptides were transformed into yeast
      cells for expression of the peptides; the results showed that the former peptide
      was expressed as single component, while the latter was expressed as a mixture of
      two components (isomer 1 and isomer 2). The expression results together with
      studies of circular dichoism, disulfide rearrangement, and refolding lead us to
      deduce that isomer 1 corresponds to the swap form and the isomer 2 corresponds to
      the native form. We further demonstrate that the sequence 1-4 plus B9 of IGF-1 B
      domain can make PIP fold into two structures, while sequence 1-5 of insulin B
      chain can make IGF-1 fold into one unique structure. In other words, it is the
      IGF-1 B-domain sequence that 1-4 allows IGF-1 folding into two thermodynamically
      stable tertiary structures; this sequence plus its residue B9E can change PIP
      folding behavior from folding into one unique structure to two thermodynamically
      stable structures, like that of IGF-1.

PMID- 17198393
TI  - Mapping the interaction of cofilin with subdomain 2 on actin.
AB  - Cofilin, a member of the actin-depolymerizing factor (ADF)/cofilin family of
      proteins, is a key regulator of actin dynamics. Cofilin binds to monomer (G-) and
      filamentous (F-) actin, severs the filaments, and increases their turnover rate.
      Electron microscopy studies suggested cofilin interactions with subdomains 2 and
      1/3 on adjacent actin protomers in F-actin. To probe for the presence of a
      cryptic cofilin binding site in subdomain 2 in G-actin, we used transglutaminase
      mediated cross-linking, which targets Gln41 in subdomain 2. The cross-linking
      proceeded with up to 85% efficiency with skeletal alpha-actin and WT yeast actin,
      yielding a single product corresponding to a 1:1 actin-cofilin complex but was
      strongly inhibited in Q41C yeast actin (in which Q41 was substituted with
      cysteine). LC-MS/MS analysis of the proteolytic fragments of this complex mapped
      the cross-linking to Gln41 on actin and Gly1 on recombinant yeast cofilin. The
      actin-cofilin (AC) heterodimer was purified on FPLC for analytical
      ultracentrifugation and electron microscopy analysis. Sedimentation equilibrium
      and velocity runs revealed oligomers of AC in G-actin buffer. In the presence of
      excess cofilin, the covalent AC heterodimer bound a second cofilin, forming a 2:1
      cofilin/actin complex, as revealed by sedimentation results. Under polymerizing
      conditions the cross-linked AC formed mostly short filaments, which according to
      image reconstruction were similar to uncross-linked actin-cofilin filaments.
      Although a majority of the cross-linking occurs at Gln41, a small fraction of the
      AC cross-linked complex forms in the Q41C yeast actin mutant. This secondary
      cross-linking site was sequenced by MALDI-MS/MS as linking Gln360 in actin to
      Lys98 on cofilin. Overall, these results demonstrate that the region around Gln41
      (subdomain 2) is involved in a weak binding of cofilin to G-actin.

PMID- 17198394
TI  - Global structure analysis of acid-unfolded myoglobin with consideration to
      effects of intermolecular coulomb repulsion on solution X-ray scattering.
AB  - To obtain information on the global structure of protein in the acid-unfolded
      (AU) state, the structure of apomyoglobin (apoMb) was analyzed by using the
      solution X-ray scattering (SXS) method. SXS profiles were obtained over a wide
      range of protein concentrations, 1-18 mg mL-1, under strongly acidic conditions.
      From analysis of the SXS profile extrapolated to a zero protein concentration,
      the mean square radius, Rsq, of AU-apoMb at 20 mM HCl was estimated to be 4.81 +/
      0.31 nm. This estimate is more than 1.3 nm larger than those of 3.0-3.5 nm
      reported thus far. The difference originates from the fact that effects of
      Coulomb repulsive forces acting between AU-apoMb molecules have not been
      correctly taken into account in the conventional analysis. In fact, even at a low
      protein concentration of 1 mg mL-1 close to the limit of measurement in the
      present SXS method, the solution condition applicable to estimating accurately
      structural parameters of AU-apoMb is very limited. At HCl concentrations lower
      than 10 mM, the scattering intensity at a small scattering vector decreases
      remarkably through the effect of intermolecular repulsive forces and the forward
      scattering intensity is significantly lower than the estimate from the partial
      specific volume of protein. On the other hand, at HCl concentrations higher than
      50 mM, some compact molten-globule-like structures emerge. As a result, the
      intermediate concentration of 20 mM HCl is the best choice of the solution
      condition for determining Rsq of AU-apoMb. The effect of intermolecular Coulomb
      repulsion on the SXS profile of AU-apoMb is at its maximum for forward scattering
      and decreases monotonously with an increase in the scattering angle to be
      virtually negligible at K approximately 0.63 nm(-1). Whereas urea-denatured apoMb
      shows a SXS profile typical of Gaussian chains, the intrinsic SXS profile of AU
      apoMb differs significantly from those of Gaussian chains.

PMID- 17198395
TI  - Inhibition of proteinase K activity by copper(II) ions.
AB  - Disease-related prion protein, PrPSc, can be distinguished from its normal
      cellular precursor, PrPC, by its detergent insolubility and partial resistance to
      proteolysis. Several studies have suggested that copper(II) ions can convert PrPC
      to a proteinase K-resistant conformation; however, interpretation of these
      studies is complicated by potential inhibition of proteinase K (PK) by copper(II)
      ions. Here we have examined directly the kinetic and equilibrium effects of
      copper(II) ions on PK activity using a simple synthetic substrate, p-nitrophenyl
      acetate. We show that at equilibrium two to three copper(II) ions bind
      stoichiometrically to PK and destroy its activity (Kd < 1 microM). This
      inhibition has two components, an initial reversible and weak binding phase and a
      slower, irreversible abolition of activity with a half-time of 6 min at
      saturating copper(II) ion concentrations. Copper(II) ions produce a similar
      biphasic inhibition of PK activity in the presence of brain homogenate but only
      when the copper(II) ion concentration exceeds that of the chelating components
      present in brain tissue. Under these conditions, the apparent resistance of PrPC
      to proteolysis by PK appears to be directly attributable to the inhibition of PK
      activity by copper(II) ions.

PMID- 17198396
TI  - Isolation and characterization of phage-displayed single chain antibodies
      recognizing nonreducing terminal mannose residues. 1. A new strategy for
      generation of anti-carbohydrate antibodies.
AB  - Phage-display technology is probably the best available strategy to produce
      antibodies directed against various carbohydrate moieties since conventional
      hybridoma technologies have yielded mostly low-affinity antibodies against a
      limited number of carbohydrate antigens. Because of difficulties in
      immobilization of carbohydrate antigens onto plastic plates, however, the same
      procedures used for protein antigens cannot be readily applied. We adapted phage
      display technology to generate human single chain antibodies (scFvs) using
      neoglycolipids as antigens. This study describes the isolation and
      characterization of phage-displayed antibodies (phage Abs) that recognized
      nonreducing terminal mannose residues. We first constructed a phage Ab library
      with a large repertoire using CDR shuffling and VL/VH shuffling methods with
      unique vector constructs. The library was subjected to four rounds of panning
      against neoglycolipids synthesized from mannotriose (Man3) and
      dipalmitoylphosphatidylethanolamine (DPPE) by reductive amination. Of 672 clones
      screened by enzyme-linked immunosorbent assay (ELISA) using Man3-DPPE as an
      antigen, 25 positive clones encoding scFvs with unique amino acid sequences were
      isolated as candidates for phage Abs against Man3 residues. TLC-overlay assays
      and surface plasmon resonance analyses revealed that selected phage Abs bound to
      neoglycolipids bearing mannose residues at nonreducing termini. In addition,
      binding of the phage Ab to RNase B carrying high mannose type oligosaccharides
      but not to fetuin carrying complex type and O-linked oligosaccharides was
      confirmed. Furthermore, first round characterization of scFvs expressed from
      respective phages indicated good affinity and specificity for nonreducing
      terminal mannose residues. These results demonstrated the usefulness of this
      strategy in constructing human scFv against various carbohydrate antigens.
      Further studies on the purification and characterization of these scFvs are
      presented in an accompanying paper in this issue.

PMID- 17198397
TI  - Isolation and characterization of phage-displayed single chain antibodies
      recognizing nonreducing terminal mannose residues. 2. Expression, purification,
      and characterization of recombinant single chain antibodies.
AB  - Since phage-display technology is probably the best available strategy to produce
      antibodies directed against various carbohydrate moieties, we employed phage
      display technology to generate human single chain antibodies (scFvs) using
      neoglycolipids as carbohydrate antigens. An accompanying paper in this issue
      describes how phage-displayed antibodies (phage Abs) that recognized nonreducing
      terminal mannose residues were isolated and characterized. In this study, four
      independent scFv genes, isolated by a mannotriose (Man3)-bearing lipid as an
      antigen as previously described, were used to construct expression vectors to
      produce soluble scFv proteins in quantity. Both bacterial and mammalian
      expression systems were used to produce glutathione S-transferase-scFv fusion
      proteins and scFv-human IgG1 Fc conjugates, respectively. The expressed scFv
      fusion proteins were purified to apparent homogeneity with yields of
      approximately 1 and 48 mg, from 1 L of bacterial culture and myeloma cell media,
      respectively. Surface plasmon resonance and ELISA analyses confirmed that
      purified scFv proteins showed Man3 specificity. The humanized antibody in scFv-Fc
      form, derived from clone 5A3, was a disulfide-liked dimer with a molecular mass
      of 108 kDa. According to a bivalent model, the kinetics parameters of its binding
      to Man3 were determined to be ka = 4.03 x 104 M-1 s-1, kd = 5.77 x 10-4 s-1, KA =
      6.98 x 107 M-1, and KD = 1.43 x 10-8 M. This study thus established the
      foundation for isolation of carbohydrate-specific scFv genes and eventual
      production of humanized scFv-Fc type antibodies.

PMID- 17198398
TI  - Arg-Pro-X-Ser/Thr is a consensus phosphoacceptor sequence for the meiosis
      specific Ime2 protein kinase in Saccharomyces cerevisiae.
AB  - Ime2 is a meiosis-specific protein kinase in Saccharomyces cerevisiae that is
      functionally related to cyclin-dependent kinase. Although Ime2 regulates multiple
      steps in meiosis, only a few of its substrates have been identified. Here we show
      that Ime2 phosphorylates Sum1, a repressor of meiotic gene transcription, on Thr
      306. Ime2 protein kinase assays with Sum1 mutants and synthetic peptides define a
      consensus Arg-Pro-X-Ser/Thr motif that is required for efficient phosphorylation
      by Ime2. The carboxyl residue adjacent to the phosphoacceptor (+1 position) also
      influences the efficiency of Ime2 phosphorylation with alanine being a preferred
      residue. This information has predictive value in identifying new potential Ime2
      targets as shown by the ability of Ime2 to phosphorylate Sgs1 and Gip1 in vitro
      and could be important in differentiating mitotic and meiotic regulatory
      pathways.

PMID- 17198399
TI  - Bilayer mechanical properties regulate the transmembrane helix mobility and
      enzymatic state of CD39.
AB  - CD39 can exist in at least two distinct functional states depending on the
      presence and intact membrane integration of its two transmembrane helices. In
      native membranes, the transmembrane helices undergo dynamic rotational motions
      that are required for enzymatic activity and are regulated by substrate binding.
      In this study, we show that bilayer mechanical properties regulate conversion
      between the two enzymatic functional states by modulating transmembrane helix
      dynamics. Alteration of membrane properties by insertion of cone-shaped or
      inverse cone-shaped amphiphiles or by cholesterol removal switches CD39 to the
      same enzymatic state that removal or solubilization of the transmembrane domains
      does. The same membrane alterations increase the propensity of both transmembrane
      helices to rotate within the packed structure, resulting in a structure with
      greater mobility but not an altered primary conformation. Membrane alteration
      also abolishes the ability of the substrate to stabilize the helices in their
      primary conformation, indicating a loss of coupling between substrate binding and
      transmembrane helix dynamics. Removal of either transmembrane helix mimics the
      effect of membrane alteration on the mobility and substrate sensitivity of the
      remaining helix, suggesting that the ends of the extracellular domain have
      intrinsic flexibility. We suggest that a mechanical bilayer property, potentially
      elasticity, regulates CD39 by altering the balance between the stability and
      flexibility of its transmembrane helices and, in turn, of its active site.

PMID- 17198400
TI  - Thermodynamic investigation into the mechanisms of proton-coupled electron
      transfer events in heme protein maquettes.
AB  - To study the engineering requirements for proton pumping in energy-converting
      enzymes such as cytochrome c oxidase, the thermodynamics and mechanisms of proton
      coupled electron transfer in two designed heme proteins are elucidated. Both heme
      protein maquettes chosen, heme b-[H10A24]2 and heme b-[delta7-His]2, are four
      alpha-helix bundles that display pH-dependent heme midpoint potential
      modulations, or redox-Bohr effects. Detailed equilibrium binding studies of
      ferric and ferrous heme b with these maquettes allow the individual contributions
      of heme-protein association, iron-histidine ligation, and heme-protein
      electrostatics to be elucidated. These data demonstrate that the larger, less
      well-structured [H10A24]2 binds heme b in both oxidation states tighter than the
      smaller and more well-structured [Delta7-His]2 due to a stronger porphyrin
      protein hydrophobic interaction. The 66 mV (1.5 kcal/mol) difference in their
      heme reduction potentials observed at pH 8.0 is due mostly to stabilization of
      ferrous heme in [H10A24]2 relative to [delta7-His]2. The data indicate that
      porphyrin-protein hydrophobic interactions and heme iron coordination are
      responsible for the Kd value of 37 nM for the heme b-[delta7-His]2 scaffold,
      while the affinity of heme b for [H10A24]2 is 20-fold tighter due to a
      combination of porphyrin-protein hydrophobic interactions, iron coordination, and
      electrostatic effects. The data also illustrate that the contribution of bis-His
      coordination to ferrous heme protein affinity is limited, <3.0 kcal/mol. The
      1H+/1e- redox-Bohr effect of heme b-[H10A24]2 is due to the greater absolute
      stabilization of the ferric heme (4.1 kcal/mol) compared to the ferrous heme (1.4
      kcal/mol) binding upon glutamic acid deprotonation, i.e., an electrostatic
      response mechanism. The 2H+/1e- redox-Bohr effect observed for heme b-[delta7
      His]2 is due to histidine protonation and histidine dissociation of ferrous heme
      b upon reduction, i.e., a ligand loss mechanism. These results indicate that the
      contribution of porphyrin-protein hydrophobic interactions to heme affinity is
      critical to maintaining the heme bound in both oxidation states and eliciting an
      electrostatic response from these designed heme protein scaffolds.

PMID- 17198402
TI  - Repression of Staphylococcus aureus SrrAB using inducible antisense srrA alters
      growth and virulence factor transcript levels.
AB  - Our laboratory has previously identified the staphylococcal respiratory response
      (SrrAB), a Staphylococcus aureus two-component system that acts in the global
      regulation of virulence factors. In strain RN4220, SrrAB downregulated production
      of agr RNAIII, protein A, and TSST-1, particularly under low-oxygen conditions.
      Work by another group showed that SrrAB regulates energy metabolism genes and
      indicated that SrrAB may regulate energy transduction in response to changes in
      oxygen availability. In this study we investigate the role of SrrAB in regulating
      RNAIII, tst, spa, icaR, and icaA in a clinical isolate of S. aureus, MN8. We
      employ an inducible antisense vector, pYJY4, in order to repress transcription of
      srrAB. Transcript levels were assessed by reverse transcription followed by
      quantitative PCR. Repression of srrAB in rich media under aerobic growth
      conditions shows that SrrAB is required for expression of tst, spa, and icaR
      transcripts at wild-type levels. Comparisons made between rich media under
      aerobic conditions vs low-oxygen conditions show that srrAB transcript levels are
      not altered by oxygen alone. Previous studies performed on strain RN4220 under
      low-oxygen conditions indicate that SrrAB represses tst and spa transcript when
      the amount of oxygen is limited. We propose that, under aerobic conditions, SrrAB
      enhances the levels of tst, spa, and icaR, while under low-oxygen conditions,
      SrrAB decreases the levels of these three transcripts.

PMID- 17198401
TI  - Interaction between cytochrome caa3 and F1F0-ATP synthase of alkaliphilic
      Bacillus pseudofirmus OF4 is demonstrated by saturation transfer electron
      paramagnetic resonance and differential scanning calorimetry assays.
AB  - Interaction between the cytochrome caa3 respiratory chain complex and F1F0-ATP
      synthase from extremely alkaliphilic Bacillus pseudofirmus OF4 has been
      hypothesized to be required for robust ATP synthesis by this alkaliphile under
      conditions of very low protonmotive force. Here, such an interaction was probed
      by differential scanning calorimetry (DSC) and by saturation transfer electron
      paramagnetic resonance (STEPR). When the two purified complexes were embedded in
      phospholipid vesicles individually [(caa3)PL, (F1F0)PL)] or in combination [(caa3
      + F1F0)PL] and subjected to DSC analysis, they underwent exothermic
      thermodenaturation with transition temperatures at 69, 57, and 46/75 degrees C,
      respectively. The enthalpy change, deltaH (-8.8 kcal/mmol), of protein
      phospholipid vesicles containing both cytochrome caa3 and F1F0 was smaller than
      that (-12.4 kcal/mmol) of a mixture of protein-phospholipid vesicles formed from
      each individual electron transfer complex [(caa3)PL + (F1F0)PL]. The rotational
      correlation time of spin-labeled caa3 (65 micros) in STEPR studies increased
      significantly when the complex was mixed with F1F0 prior to being embedded in
      phospholipid vesicles (270 micros). When the complexes were reconstituted
      separately and then mixed together, or either mitochondrial cytochrome bc1 or
      F1F0 was substituted for the alkaliphile F1F0, the correlation time was unchanged
      (65-70 micros). Varying the ratio of the two alkaliphile complexes in both the
      DSC and STEPR experiments indicated that the optimal stoichiometry is 1:1. These
      results demonstrate a physical interaction between the cytochrome caa3 and F1F0
      ATP synthase from B. pseudofirmus OF4 in a reconstituted system. They support the
      suggestion that such an interaction between these complexes may contribute to
      sequestered proton transfers during alkaliphile oxidative phosphorylation at high
      pH.

PMID- 17198403
TI  - Trans protein splicing of cyanobacterial split inteins in endogenous and
      exogenous combinations.
AB  - Inteins are autocatalytic protein domains that post-translationally excise from
      protein precursors and ligate their flanking regions with a peptide bond, in a
      process called protein splicing. Intein-containing DNA polymerases of
      cyanobacteria and nanoarchaea are naturally split into two separate genes at
      their intein domain. Such naturally occurring split inteins rapidly self
      associate and reconstitute protein-splicing activity in trans. Here, we analyze
      the in vitro protein-splicing activity of three naturally split inteins from
      diverse cyanobacteria: Oscillatoria limnetica, Thermosynechococcus vulcanus, and
      Nostoc sp. PCC7120. N- and C-terminal halves of these split inteins were mixed in
      nine combinations, resulting in three endogenous (wild-type) and six exogenous
      combinations. Protein splicing was detected in all split-intein combinations,
      despite a 30-50% sequence variation between the homologous proteins. Splicing
      activity proceeded under a variety of conditions, including the presence of
      denaturants and reductants and high temperature, ionic strength, and viscosity.
      Still, in a high concentration of salt (2 M) or urea (6 M), specific combinations
      spliced significantly better than others. Additionally, copper ions were found to
      inhibit trans splicing in a reversible double-lock reaction. Our comparative
      analysis of naturally split inteins in endogenous and exogenous combinations
      demonstrates the modularity of trans protein-splicing elements and their robust
      activity. It suggests tight interactions between split-intein halves and
      conditions for modifying the specificity of intein parts. These results promote
      the biotechnological use of split inteins for controlled assembly of protein
      fragments either in vivo or in vitro and under moderate or extreme conditions.

PMID- 17198405
TI  - Influence of electron-attractor substituents on the magnetic properties of Ni(II)
      string complexes.
AB  - Density functional theory calculations carried out on the anionic Ni(II) chain
      complexes {trinickeltetrakis[2,6-bis(amido)pyridine]}2- and
      {trinickeltetrakis[N,N'-bis(sulfonyl)pyridyldiamido]}2- show that the electron
      attractor character of the sulfonyl substituent modifies the basicity of the
      amido ligand ends so as to raise the electronic state of the underlying metal
      atom from low spin (S = 0) to high spin (S = 1). The computed elongation of the
      outermost Ni-N bonds with the grafting of SO2H substituents is in agreement with
      this interpretation.

PMID- 17198404
TI  - X-ray absorption spectroscopic characterization of the molybdenum site of
      Escherichia coli dimethyl sulfoxide reductase.
AB  - Structural studies of dimethyl sulfoxide (DMSO) reductases were hampered by
      modification of the active site during purification. We report an X-ray
      absorption spectroscopic analysis of the molybdenum active site of Escherichia
      coli DMSO reductase contained within its native membranes. The enzyme in these
      preparations is expected to be very close to the form found in vivo. The oxidized
      active site was found to have four Mo-S ligands at 2.43 A, one Mo=O at 1.71 A,
      and a longer Mo-O at 1.90 A. We conclude that the oxidized enzyme is a
      monooxomolybdenum(VI) species coordinated by two molybdopterin dithiolenes and a
      serine. The bond lengths determined for E. coli DMSO reductase are very similar
      to those determined for the well-characterized Rhodobacter sphaeroides DMSO
      reductase, suggesting similar active site structures for the two enzymes.
      Furthermore, our results suggest that the form found in vivo is the
      monooxobis(molybdopterin) species.

PMID- 17198406
TI  - Base-stabilized amidodiarsenes: synthesis, structure, and theoretical studies.
AB  - The guanidinato- or amidinato-bridged diarsenes [As2{mu-(ArN)2CR}2] (Ar =
      C6H3Pri2-2,6; R = N(C6H11)2, NPri2, or But) have been prepared by reduction of
      the corresponding As(III) precursors, [Cl2As{kappa2-N,N'-(ArN)2CR}]. Theoretical
      studies suggest that the As-As bonds of the dimers have significant double-bond
      character, the sigma and pi components of which are derived mainly from As p
      orbital overlaps.

PMID- 17198407
TI  - Homo- and heteroleptic complexes of four-membered group 13 metal(I) N
      heterocyclic carbene analogues with group 10 metal(0) fragments.
AB  - A series of complexes between recently developed four-membered group 13 metal(I)
      heterocycles and group 10 metal(0) fragments have been prepared and structurally
      characterized. One prepared complex, [Pt{Ga[N(Ar)]2CNCy2}3] (Ar = C6H3Pri2-2,6;
      Cy = cyclohexyl), possesses the shortest Pt-Ga bonds yet reported, the covalent
      components of which are suggested by theoretical studies to have significant pi
      character.

PMID- 17198408
TI  - Synthesis and characterization of cationic tungsten(V) methylidynes.
AB  - Cationic tungsten(V) methylidynes [L4W(X)[triple bond]CH]+[B(C6F5)4]- [L = PMe3,
      0.5dmpe (dmpe = Me2PCH2CH2PMe2), X = Cl, OSO2CF3] have been prepared in high
      yield by a one-electron oxidation of the neutral tungsten(IV) methylidynes
      L4W(X)[triple bond]CH with [Ph3C]+[B(C6F5)4]-. The ease and reversibility of the
      one-electron oxidation of L4W(X)[triple bond]CH were demonstrated by cyclic
      voltammetry in tetrahydrofuran (E1/2 is approximately -0.68 to -0.91 V vs Fc).
      The paramagnetic d1 (S = 1/2) complexes were characterized in solution by
      electron spin resonance (g = 2.023-2.048, quintets due to coupling to 31P) and
      NMR spectroscopy and Evans magnetic susceptibility measurements (mu = 2.0-2.1
      muB). Single-crystal X-ray diffraction showed that the cationic methylidynes are
      structurally similar to the neutral precursor methylidynes. In addition, the
      neutral (PMe3)4W(Cl)[triple bond]CH was deprotonated with a strong base at the
      trimethylphosphine ligand to afford (PMe3)3(Me2PCH2)W[triple bond]CH, a
      tungsten(IV) methylidyne complex that features a (dimethylphosphino)methyl
      ligand.

PMID- 17198409
TI  - Cyanide-bridged Mn(III)-Fe(III) bimetallic complexes based on the pentacyano(1
      methylimidazole)ferrate(III) building block: structure and magnetic
      characterizations.
AB  - Seven cyanide-bridged bimetallic complexes have been synthesized by the reaction
      of [Fe(1-CH3im)(CN)5]2- with Mn(III) Schiff base complexes. Their crystal
      structure and magnetic properties have been characterized. Five complexes, [Mn2(5
      Brsalen)2Fe(CN)5(1-CH3im)] x H2O (1), [Mn2(5-Clsalen)2(H2O)2Fe(CN)5(1-CH3im)] x
      H2O (2), [Mn2(5-Clsaltn)2(H2O)2Fe(CN)5(1-CH3im)] (3), [Mn2(5
      Clsaltmen)2(H2O)2Fe(CN)5(1-CH3im)] x H2O (4), and [Mn2(5
      Brsaltmen)2(H2O)2Fe(CN)5(1-CH3im)] x CH3OH (5), are neutral and trinuclear with
      two [Mn(SB)]+ (SB2- = Schiff base ligands) and one [Fe(1-CH3im)(CN)5]2-. Complex
      {[Et4N][Mn(acacen)Fe(CN)5(1-CH3im)]}n x 6nH2O (6) is one-dimensional with
      alternate [Mn(acacen)]+ and [Fe(CN)5(1-CH3im)]2- units. The two-dimensional
      complex {[Mn4(saltmen)4Fe(CN)5(1-CH3im)]}n[ClO4]2n x 9nH2O (7) consists of Mn4Fe
      units which are further connected by the phenoxo oxygen atoms. Magnetic studies
      show the presence of ferromagnetic Mn(III)-Fe(III) coupling in the trinuclear
      compounds with the magnetic coupling constant (J) ranging from 4.5 to 6.0 cm-1,
      based on the Hamiltonian H = -2JSFe(SMn(1) + SMn(2)). Antiferromagnetic
      interaction has been observed in complex 6, whereas ferromagnetic coupling occurs
      in complex 7. Complexes 6 and 7 exhibit long-range magnetic ordering with a TN
      value of 4.0 K for 6 and Tc of 4.8 K for 7. Complex 6 shows metamagnetic behavior
      at 2 K, and complex 7 possesses a hysteresis loop with a coercive field of 500
      Oe, typical of a soft ferromagnet.

PMID- 17198410
TI  - Speciation of the catalytic oxygen evolution system: [MnIII/IV2(mu
      O)2(terpy)2(H2O)2](NO3)3 + HSO5-.
AB  - [MnIII/IV2(-O)2(terpy)2(OH2)2](NO3)3 (1, where terpy = 2,2':6'2' '-terpyridine) +
      oxone (2KHSO5 x KHSO4 x K2SO4) provides a functional model system for the oxygen
      evolving complex of photosystem II that is based on a structurally relevant Mn-(
      O)2-Mn moiety (Limburg, J.; et al. J. Am. Chem. Soc. 2001, 123, 423-430). In this
      study, electron paramagnetic resonance, ultraviolet-visible spectroscopy,
      electrospray ionization mass spectrometry, X-ray absorption spectroscopy, and gas
      phase stable isotope ratio mass spectrometry were utilized to identify the title
      compounds in the catalytic solution. We find that (a) O2 evolution does not
      proceed through heterogeneous catalysis by MnO2 or other decomposition products,
      that (b) O atoms from solvent water are incorporated into the evolved O2 to a
      significant extent but not into oxone, that (c) the MnIII/IV2 title compound 1 is
      an active precatalyst in the catalytic cycle of O2 evolution with oxone, while
      the MnIV/IV2 oxidation state is not, and that (d) the isotope label incorporation
      in the evolved O2, together with points a-c above, is consistent with a mechanism
      involving competing reactions of oxone and water with a "MnV=O" intermediate in
      the O-O bond-forming step.

PMID- 17198411
TI  - Structural characterization of Al10O6iBu16(mu-H)2, a high aluminum content
      cluster: further studies of methylaluminoxane (MAO) and related aluminum
      complexes.
AB  - The first structurally characterized isobutyl-containing aluminoxane compound is
      presented. The Al10O6iBu16(mu-H)2 (I) cluster is produced from neat octakis
      isobutyltetraluminoxane (Al4O2iBu8) at 80 degrees C in 6-8 h followed by slow
      crystallization. The crystal is triclinic (space group P1) with the molecule
      lying on an inversion center. This aluminoxane contains both nearly linear,
      154(2) degrees, aluminum-bridging hydrides and three-coordinate aluminum sites.
      Solid-state 27Al magic-angle spinning (MAS) NMR experiments were done at 19.6 and
      40 T (833 MHz and 1.703 GHz, 1H) and at 30-35 kHz spinning speeds, leading to the
      determination of the Cq and eta values for the two four-coordinate Al sites and a
      lower limit of Cq for the three-coordinate Al site. Geometry-optimized restricted
      Hartree-Fock calculations at the double-zeta level of an idealized structure
      (methyl substituted, D2h geometry) yielded Cq and eta in close agreement with
      experiment; Cq agrees within 3 MHz.

PMID- 17198412
TI  - Weak-field anions displace the histidine ligand in a synthetic heme peptide but
      not in N-acetylmicroperoxidase-8: possible role of heme geometry differences.
AB  - We have recently reported that aquo and thioether complexes of the ferric
      cytochrome c heme peptide N-acetylmicroperoxidase-8 (FeIII-1) exhibit greater low
      spin character than do the corresponding complexes of a synthetic, water-soluble,
      monohistidine-ligated heme peptide (FeIII-2; Cowley, A. B.; Lukat-Rodgers, G. S.;
      Rodgers, K. R.; Benson, D. R. Biochemistry 2004, 43, 1656-1666). Herein we report
      results of studies showing that weak-field ligands bearing a full (fluoride,
      chloride, hydroxide) or partial (phenoxide, thiocyanate) negative charge on the
      coordinating atom trigger dissociation of the axial His ligand in FeIII-2 but not
      in FeIII-1. We attribute the greater sensitivity of His ligation in FeIII-1 to
      weak-field anionic ligands than to weak-field neutral ligands to the following
      phenomena: (1) anionic ligands pull FeIII further from the mean plane of a
      porphyrin than do neutral ligands, which will have the effect of straining the
      His-Fe bond in FeIII-2, and (2) heme in FeIII-2 is likely to undergo a modest
      doming distortion following anion binding that will render the His-ligated side
      of the porphyrin concave, thereby increasing porphyrin/ligand steric
      interactions. We propose that ruffling of the heme in FeIII-1 is an important
      factor contributing to its ability to resist His dissociation by weak-field
      anions. First, ruffling should allow His to more closely approach the porphyrin
      than is possible in FeIII-2, thereby reducing bond strain following anion
      binding. Second, the ruffling deformation in FeIII-1, which is enforced by the
      double covalent heme-peptide linkage, will almost certainly prevent significant
      porphyrin doming.

PMID- 17198414
TI  - Design of molecular scaffolds based on unusual geometries for magnetic modulation
      of spin-diverse complexes with selective redox response.
AB  - A weakly coupled heterometallic [CuFe] complex has been prepared in which the
      metal centers are coordinated to a new electroactive ligand. The spin-diverse
      system delivers distinct ground states upon application of selective redox
      potentials. Ligand oxidation fosters radical generation, and the initial ground
      state associated with a weakly coupled [CuFe] core switches to a ground state
      associated with the [Fe-radical] coupling; the Cu(II) ion remains uncoupled. A
      third state is obtained upon reduction of the cupric center and in absence of the
      radical. The possibilities and limitations of these systems are discussed.

PMID- 17198415
TI  - fac-{Ru(CO)3}2+-core complexes and design of metal-based drugs. synthesis,
      structure, and reactivity of Ru-thiazole derivative with serum proteins and
      absorption-release studies with acryloyl and silica hydrogels as carriers in
      physiological media.
AB  - The reaction of [Ru2(CO)6Cl4], 1, with excess THZ (1,3-thiazole) in absolute
      ethanol at 55 degrees C produces fac-[Ru(CO)3Cl2(THZ)], 2, in high yield.
      [Ru(CO)2Cl2(THZ)2], 3, is formed at higher temperature (ca 70 degrees C) and
      higher concentration of THZ. The X-ray structures of the new compounds have been
      determined, and density functional studies performed at the hybrid
      B3LYP/(Lanl2DZ, Ru; 6-311+G**, CHClNOS) level allowed the estimation of the
      structures of several conformers as well as that of their relative total
      electronic energies. Compound 2 is soluble (slowly) in aqueous media, where it
      reacts with the transport proteins bovine serum albumin (BSA) and human
      apotransferrin (HTF), and at a lower extent with calf thymus DNA (CT-DNA) and
      with guanosine-5'-monophosphate (GMP). The complex molecule is adsorbed by
      certain synthetic acryloyl polymers that have terminal carboxylate functions and
      is embedded in silica gels when these latter are prepared in the presence of a
      solution of 2. Ruthenium species are slowly released from the loaded gels into
      physiological solutions at pH 7.4. The reactivity of 2 with biomolecules and
      synthetic hydrogels makes it a compound of interest for anticancer and
      antimetastases tests.

PMID- 17198413
TI  - Quantitative geometric descriptions of the belt iron atoms of the iron-molybdenum
      cofactor of nitrogenase and synthetic iron(II) model complexes.
AB  - Six of the seven iron atoms in the iron-molybdenum cofactor of nitrogenase
      display an unusual geometry, which is distorted from the tetrahedral geometry
      that is most common in iron-sulfur clusters. This distortion pulls the iron along
      one C3 axis of the tetrahedron toward a trigonal pyramid. The trigonal pyramidal
      coordination geometry is rare in four-coordinate transition metal complexes. In
      order to document this geometry in a systematic fashion in iron(II) chemistry, we
      have synthesized a range of four-coordinate iron(II) complexes that vary from
      tetrahedral to trigonal pyramidal. Continuous shape measures are used for a
      quantitative comparison of the stereochemistry of the Fe atoms in the iron
      molybdenum cofactor with those of the presently and previously reported model
      complexes, as well as with those in polynuclear iron-sulfur compounds. This
      understanding of the iron coordination geometry is expected to assist in the
      design of synthetic analogues for intermediates in the nitrogenase catalytic
      cycle.

PMID- 17198416
TI  - Synthesis and characterization of silyldichloramines, their reactions with F-
      ions, instability of N2Cl2 and NCl2-, and formation of NCl3.
AB  - Only two silyldichloramines, (C6H5)3SiNCl2 and (CH3)3SiNCl2, have been reported
      in the literature. The synthesis of the former was successfully repeated, and its
      structure was established by single-crystal X-ray diffraction and vibrational
      spectroscopy. Attempts to prepare (CH3)3SiNCl2 were unsuccessful; however, a new
      trialkylsilyldichloramine, t-BuMe2Si-NCl2, was prepared and characterized by
      Raman and multinuclear NMR spectroscopy. The reaction of t-BuMe2SiNCl2 with
      (CH3)4NF in CHF3 solution at -78 degrees C, followed by removal of all volatile
      products at -30 degrees C, produced the expected t-BuMe2SiF byproduct and a white
      solid consisting of NCl3 absorbed on Me4NCl. The NCl3 could be reversibly
      desorbed from the substrate and was identified as a neat liquid at room
      temperature by Raman spectroscopy. The observed final reaction products are
      consistent with the formation of an unstable N(CH3)4+NCl2- intermediate which
      decomposes to N(CH3)4+Cl- and NCl molecules which can dimerize to N2Cl2.
      Theoretical calculations confirm that NCl2- can readily lose Cl- and that N2Cl2
      also possesses a low barrier toward loss of N2 to give chlorine atoms and, thus,
      can account for the formation of NCl3.

PMID- 17198417
TI  - Control of two-electron four-center (2e-/4c) C-C bond formation observed for
      tetracyanoethenide dimerization, [TCNE]2(2-).
AB  - Cu(PPh3)3(TCNE) (TCNE = tetracyanoethylene) and 14 other examples form [TCNE]22-
      dimers possessing a long 2.89 +/- 0.05 A two-electron four-center (2e-/4c) C-C
      bond in the solid state. This bond arises from the overlap of the b2g pi* singly
      occupied molecular orbital (SOMO) on each [TCNE]*- fragment, forming a filled
      bonding orbital of b2u symmetry, and the stabilizing effect of the cation...anion
      interactions in the crystal that exceed the anionic repulsion. In contrast,
      Mn(C5H5)(CO)2(TCNE) exhibits a related, but different, [TCNE]*-...TCNE]*- motif
      in the solid state that lacks the 2e-/4c C-C bonding. To better understand the
      unusual nature of 2e-/4c C-C bonding, the genesis of the differences between
      their respective pi-[TCNE]*-...TCNE]*- interactions was sought. The lack of 2e
      /4c C-C bond formation is attributed to the weaker radical character of the
      [TCNE]*- ligand, which has a total spin population of only 0.5 electron, half of
      that required for two S = 1/2 [TCNE]*- moieties to form a [TCNE]22- dimer. Hence,
      the antiferromagnetic MnII-[TCNE]*- intramolecular interaction (between the
      formally S = 1/2 Mn-bound [TCNE]*- and the paramagnetic Mn(II)) dominates over
      the intermolecular pi-[TCNE]*--[TCNE]*- spin coupling (between two S = 1/2
      [TCNE]*- needed to form [TCNE]22-). Therefore, by selecting specific metal ions
      that can interact with sigma-[TCNE]*-, dimerization forming [TCNE]22- can be
      favored or disfavored.

PMID- 17198418
TI  - Insights into the mechanism of electrocatalytic hydrogen evolution mediated by
      Fe2(S2C3H6)(CO)6: the simplest functional model of the Fe-hydrogenase active
      site.
AB  - The di-iron complex Fe2(S2C3H6)(CO)6 (a), one of the simplest functional models
      of the Fe-hydrogenases active site, is able to electrocatalyze proton reduction.
      In the present study, the H2 evolving path catalyzed by a has been characterized
      using density functional theory. It is showed that, in the early stages of the
      catalytic cycle, a neutral mu-H adduct is formed; monoelectron reduction and
      subsequent protonation can give rise to a diprotonated neutral species (a-muH
      SH), which is characterized by a mu-H group, a protonated sulfur atom, and a CO
      group bridging the two iron centers, in agreement with experimental IR data
      indicating the formation of a long-lived mu7-CO species. H2 release from a-muH
      SH, and its less stable isomer a-H2 is kinetically unfavorable, while the
      corresponding monoanionic compounds (a-muH-SH- and a-H2-) are more reactive in
      terms of dihydrogen evolution, in agreement with experimental data. The key
      species involved in electrocatalysis have structural features different from the
      hypothetical intermediates recently proposed to be involved in the enzymatic
      process, an observation that is possibly correlated with the reduced catalytic
      efficiency of the biomimetic di-iron assembly.

PMID- 17198419
TI  - A density functional theory study of the electronic properties of Os(II) and
      Os(III) complexes immobilized on Au(111).
AB  - We present a density functional theory (DFT) study of an osmium polypyridyl
      complex adsorbed on Au(111). The osmium polypyridyl complex [Os(bpy)2(P0P)Cl]n+
      [bpy is 2,2'-bipyridine, P0P is 4,4'-bipyridine, n = 1 for osmium(II), and n = 2
      for osmium(III)] is bound to the surface through the free nitrogen of the P0P
      ligand. The calculations illuminate electronic properties relevant to recent
      comprehensive characterization of this class of osmium complexes by
      electrochemistry and electrochemical scanning tunneling microscopy. The optimized
      structures for the compounds are in close agreement with crystallographic
      structures reported in the literature. Oxidation of the complex has little effect
      on these structural features, but there is a substantial reordering of the
      electronic energy levels with corresponding changes in the electron density.
      Significantly, the highest occupied molecular orbital shifts from the metal
      center to the P0P ligand. The surface is modeled by a cluster of 28 gold atoms
      and gives a good description of the effect of immobilization on the electronic
      properties of the complexes. The results show that the coupling between the
      immobilized complex and the gold surface involves electronic polarization at the
      adsorbate/substrate interface rather than the formation of a covalent bond.
      However, the cluster is too small to fully represent bulk gold with the result
      that, contrary to what is experimentally observed, the DFT calculation predicts
      that the gold surface is more easily oxidized than the osmium(II) complex.

PMID- 17198421
TI  - Synthesis and characterization of a new layered fluoroaluminophosphate
      (C4H11NOH)3.5[Al4(PO4)5F] x 0.5H3O with extra-large 16-rings.
AB  - A new two-dimensional-layered fluoroaluminophosphate (C4H11NOH)3.5[Al4(PO4)5F] x
      0.5H3O (denoted as AlPO-CJ20) with an Al/P ratio of 4:5 has been synthesized
      solvothermally by using 2-amino-2-methyl-1-propanol as the structure-directing
      agent. Its structure was determined by single-crystal X-ray diffraction analysis
      and further characterized by solid-state NMR techniques, including 27Al, 19F -->
      27Al cross-polarization, and 31P magic angle spinning NMR. The alternation of Al
      centered tetrahedra (AlO4 and AlO3F) and PO3(=O) tetrahedra gives rise to a new
      type of 4.6.16-net sheet. The inorganic sheets are stacked in an ABAB sequence
      along the [010] direction and further held together through strong H bonds
      between protonated template molecules and P=O groups in the inorganic layers.
      Except for Mu-4, AlPO-CJ20 is the second layered aluminophosphate with an Al/P
      ratio of 4:5, and it contains the largest pore opening of 16-rings in the known
      layered aluminophosphates. Furthermore, the coordination of Al and P of
      fluoroaluminophosphates is summarized. Crystal data: (C4H11NOH)3.5[Al4(PO4)5F] x
      0.5H3O, monoclinic, C2/c (No. 15), a = 32.678(7) A, b = 12.956(3) A, c =
      21.045(4) A, beta = 115.17(3) degrees, V = 8064(3) A3, Z = 8, R1 = 0.0837 [I >
      2sigma(I)], and wR2 = 0.2428 (all data).

PMID- 17198420
TI  - Modulation of the singlet-singlet through-space energy transfer rates in cofacial
      bisporphyrin and porphyrin-corrole dyads.
AB  - A new series of relatively flexible cofacial donor-acceptor dyads for singlet
      singlet energy transfer with the corrole or etio-porphyrin free base and zinc
      porphyrin as the acceptor and donor, respectively, were synthesized and
      characterized (represented as (PMes2COx)ZnH3 (13), (PMes2CO)ZnH3 (14), and
      (PMes2CX)ZnH3 (15)) where (PMes2COx = [2-[5-(5,15-dimesitylcorrol-10-yl)
      diphenylether-2'-yl]-13,17-diethyl-2,3,7,8,12,18-hexamethylporphyrin]), (PMes2CO
      = [5-[5-(5,15-dimesitylcorrol-10-yl)-dibenzofuran-4-yl]-13,17-diethyl
      2,3,7,8,12,18-hexamethylporphyrin]), and (PMes2CX = [5-[5-(5,15-dimesitylcorrol
      10-yl)-9,9-dimethylxanthen-4-yl)]-13,17-diethyl-2,3,7,8,12,18
      hexamethylporphyrin]), respectively) along with the homobismacrocycles (DPOx)ZnH2
      (17) and (DPOx)Zn2 (18) (where (DPOx = 2,2'-bis[5-(2,8,13,17-tetraethyl-3,7,12,18
      tetramethylporphyrinyl)]diphenylether) as comparison standards. The rate for
      energy transfer (kET) extracted by the measurements of fluorescence lifetimes are
      of the same order of magnitude as those recently reported for the rigidly held
      face-to-face dyads ((DPB)ZnH2 (1), (DPX)ZnH2 (2), (DPA)ZnH2 (3), (DPO)ZnH2 (4),
      and (DPS)ZnH2 (5) where (DPB = 1,8-bis[5-(2,8,13,17-tetraethyl-3,7,12,18
      tetramethylporphyrinyl)]biphenylene), (DPX = 4,5-bis[5-(2,8,13,17-tetraethyl
      3,7,12,18-tetramethylporphyrinyl)]-9,9-dimethylxanthene), (DPA = 1,8-bis[5
      (2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]anthracene), (DPO = 4,6
      bis[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]dibenzofuran), and
      (DPS = 4,6-bis[5-(2,8,13,17-tetraethyl-3,7,12,18
      tetramethylporphyrinyl)]dibenzothiophene), respectively), but for the first time,
      it is shown that the presence of a bulky group located between the acceptor and
      the donor moiety influences the transfer rate. The presence of perpendicular
      mesityl groups on the acceptor macrocycle prevents the two macrorings from
      interacting strongly; therefore, kET is slower. On the other hand, by rendering
      the rigid spacer flexible (i.e., changing the dibenzofuran rigid spacer to the
      flexible diphenylether assembling fragment), kET increases due to stronger
      intermacrocycle interactions. This study is complemented by DFT computations
      (B3LYP/3-21G*) as a molecular modeling tool where subtle structural features
      explain the changes in kET. During the course of this study, X-ray structures of
      17 and 18 were investigated and exhibit a linear stacking of the bismacrocycles
      where intermolecular porphyrin-porphyrin interactions are observed
      (dinter(Zn...Zn) = 4.66 and 4.57 A, for 17 and 18, respectively).

PMID- 17198422
TI  - Syntheses of mixed-ligand tetranuclear gold(I)-nitrogen clusters by ligand
      exchange reactions with the dinuclear gold(I) formamidinate complex Au(2)(2,6
      Me2Ph-form)2.
AB  - The reaction of the sterically crowded dinuclear gold(I) amidinate complex
      Au2(2,6-Me2Ph-form)2, 1, with the less bulky bidentate nitrogen ligands results
      in the formation of tetranuclear gold(I) complexes. When the less bulky
      amidinate, K(4-MePh-form), A, was reacted with 1 in a 1:1 stoichiometric ratio,
      crystals containing equal amounts of the tetranuclear and dinuclear gold(I) aryl
      formamidinates, Au4(4-MePh-form)4 and Au2(2,6-Me2Ph-form)2, where 2,6-Me2Ph-form
      = B, were found in the same unit cell, 2 x 2THF: space group P, a = 10.794(11) A,
      b = 14.392(15) A, c = 25.75(3) A, alpha = 82.564(17) degrees, beta = 85.443(18)
      degrees, gamma = 82.614(19) degrees. The reaction of K(4-MePh-form), A, and 1 in
      a 1:2 ratio (excess) produced the tetranuclear complex only, 3. The potassium
      salt of the exchanged bulky ligand, K(2,6-Me2Ph-form), formed as a byproduct. The
      reaction of the dinuclear gold(I) complex Au2(2,6-Me2Ph-form)2 with the 3,5
      diphenylpyrazolate salt, K(3,5-Ph2pz), resulted in the formation of two
      tetranuclear mixed-ligand complexes, Au4(3,5-Ph2pz)2(2,6-Me2Ph-form)2 x 2THF, 4 x
      2THF (space group P21/c, a = 11.5747(19) A, b = 25.497(4) A, c = 21.221(3) A,
      beta = 96.979(3) degrees) and Au4(3,5-Ph2pz)3(2,6-Me2Ph-form) x THF, 5 x THF
      (space group P21/c, a = 23.058(5) A, b = 14.314(3) A, c = 18.528(4) A, beta =
      90.94(3) degrees. The block crystals from the tetranuclear complex, 4 x 2THF,
      contain mixed ligands with each pyrazolate ring facing an amidinate ring. The
      tetranuclear mixed ligand complex, 5 x THF, was isolated as needles with ligands
      alternating above and below the Au4 plane. The two tetranuclear mixed-ligand
      complexes emit at 490 and 530 nm, respectively, under UV excitation.

PMID- 17198423
TI  - Syntheses and structures of asymmetric Bis(silyl) niobocene hydrides.
AB  - This paper deals with the preparation and structural investigation of asymmetric
      bis(silyl) niobocene hydrides, Cp2Nb(SiHMe2)(H)(SiXMe2) (2; X = F (a), Cl (b), Br
      (c), I (d)) and Cp2Nb(SiXMe2)(H)(SiYMe2) (X,Y= F-I; X not equal Y). Complexes 2a
      d were prepared by selective electrophilic activation of the Si-H bond in
      Cp2Nb(SiHMe2)2(H). The Cp2Nb(SiXMe2)(H)(SiYMe2) complexes were prepared by
      electrophilic activation of the Si-H bond in 2a-d and, in some cases, by
      electrophilic exchange of the X halides in Cp2Nb(SiXMe2)2(H) (1) for other
      halides, Y. The structures of complexes 2b and 2c have been studied by X-ray and
      neutron diffraction (ND). The ND results unequivocally established that the
      hydride ligand in 2c is shifted toward the SiBrMe2 ligand and that in 2b is
      positioned symmetrically between two nonequivalent silyl groups, with the
      H...SiClMe2 distance being shorter because of the shorter Nb-SiClMe2 bond length.
      Analysis of the X-ray structures of complexes 2a-d and complexes
      Cp2Nb(SiXMe2)(H)(SiYMe2) shows that the largest structural distortions are
      observed for the silyl groups substituted by heavy halogen atoms. These trends
      are rationalized in terms of stronger interligand hypervalent interactions (IHI)
      Nb-H...Si-X for heavy atoms X from Group 7.

PMID- 17198424
TI  - Static magnetization of V15 cluster at ultra-low temperatures: precise estimation
      of antisymmetric exchange.
AB  - In this article, the low-temperature static (adiabatic) magnetization data of the
      nanoscopic V15 cluster present in K6[VIV15As6O42(H2O)] x 8H2O is analyzed. The
      cluster anion, which attracted much attention in the past, contains a triangular
      VIV3 array causing frustration as a function of applied field and temperature. In
      the analysis, a three-spin (S = 1/2) model of V15 was employed that includes
      isotropic antiferromagnetic exchange interaction and antisymmetric (AS) exchange
      in the most general form compatible with the trigonal symmetry of the system. It
      was shown that, along with the absolute value of AS exchange, the orientation of
      the AS vector plays a significant physical role in spin-frustrated systems. In
      this context, the role of the different components of the AS in the low
      temperature magnetic behavior of V15 was analyzed, and we were able to reach a
      perfect fit to the experimental data on the staircaselike dependence of
      magnetization versus field in the whole temperature range including extremely low
      temperature. Furthermore, it was possible for the first time to precisely
      estimate the two components of the AS vector coupling constant in a triangular
      unit, namely, the effective in-plane component, Dperpendicular, and the
      perpendicular part, Dn.

PMID- 17198426
TI  - Control of S-based aggregation: designed synthesis of NiM2 and Ni2M trinuclear
      complexes.
AB  - Modification of the nickel dithiolate metalloligand, Ni(bme-daco) [where bme-daco
      = bis(mercaptoethyl)diazacyclooctane] or Ni-1, by oxygenation of one thiolate
      into a sulfinate, Ni(mese-daco) [where mese-daco =
      (mercaptoethyl)(sulfinatoethyl)diazacyclooctane] or Ni-2, restricts the ligating
      ability to monodentate and is expected to reduce the donor ability of the
      remaining thiolate S. Nevertheless, the Ni-2 complex forms a stable thiolate S
      bound adduct of W0(CO)5, (Ni-2)W(CO)5, a complex whose upsilon(CO) IR spectrum
      reports insignificant differences in the donor abilities of Ni-1 and Ni-2 in
      (eta1-NiN2S2)W(CO)5 complexes. In the presence of the strong sulfophile CuI, a
      CuNi2 trimetallic, (Ni-2)2CuBr, was isolated. Another trimetallic, (mu-eta2-Ni
      1)[W(CO)5]2, demonstrated the Ni(bme-daco), Ni-1, unit to bridge low-valent
      metals in a transoid configuration, yielding W-W distances of over 5 A.

PMID- 17198427
TI  - Crystal-engineering studies of coordination polymers and a molecular-looped
      complex containing dipyridyl-amide ligands.
AB  - We report herein crystal-engineering studies of coordination polymers and a
      molecular-looped complex containing two dipyridyl-amide ligands, 1,3-bis-pyridin
      4-ylmethyl urea (L1) and N,N'-bis-4-methylpyridyl oxalamide (L2). The reaction of
      Cd(OAc)2 with L1 gives rise to [Cd(OAc)2(L1)]n (1), a 1-D chain through
      coordination to two L1 and two acetate ligands, and then the axial coordination
      to one urea's carbonyl group through the third L1 ligand leads 1 to form "a dimer
      of 1-D chains". With a slight change in the structural backbone from L1 to L2,
      the reaction of L2 with Cd(OAc)2 gives [Cd(OAc)2(L2)(H2O)]n (2), a 1-D chain
      structure. The reaction of Cd(NO3)2, instead of Cd(OAc)2, with L2 gives
      [Cd(NO3)2(L2)3/2]n (3), where the coordinated-anion effect on the assembly
      process has been observed for 2 and 3. The former forms a 1-D chain structure,
      and the latter, a 2-D sheet structure, depending on the coordinated anions used.
      [HgCl2(L1)]n (4) and [CuCl2(L2)]n (5), which are 1-D chain structures, show
      tetrahedral [Hg(II)] and square-planar [Cu(II)] centers, respectively.
      Surprisingly, 4 shows a typical amide-amide hydrogen bonding and 5 shows none.
      Instead, a hydrogen-bonding interaction between Cl and the amide group is
      observed in 5. Finally, the different structural conformation of L2 (a syn or
      anti form) leads to the formation of different structural motifs, coordination
      polymers (2, 3, and 5 with an anti form), and a macrocycle ([Pd(PPy)(L2)]2(ClO4)2
      (6) with a syn form, PPy = 2-phenylpyridine). Each side of the boat form of 6
      (pseudo-cyclohexane) ranges from 6.12 to 6.39 A, and the molecular loop is
      further hydrogen-bonded to stack into a 1-D hydrogen-bonded framework with a
      ladder pattern through amide-amide hydrogen bonding. Interestingly, one ClO4-
      anion is encapsulated inside the cavity through multiple CH...O interactions.

PMID- 17198425
TI  - Assignment of the ferriheme resonances of the high-spin forms of nitrophorins 1
      and 4 by 1H NMR spectroscopy: comparison to structural data obtained from X-ray
      crystallography.
AB  - In this work, we report the assignment of the majority of the ferriheme
      resonances of high-spin nitrophorins (NPs) 1 and 4 and compare them to those of
      NP2, published previously. It is found that the structures of the ferriheme
      complexes of NP1 and NP4, in terms of the orientation of the histidine imidazole
      ligand, can be described with good accuracy by NMR techniques and that the angle
      plot proposed previously for the high-spin form of the NPs (Shokhireva, T. Kh.;
      Shokhirev, N. V.; Walker, F. A. Biochemistry 2003, 42, 679-693) describes the
      angle of the effective nodal plane of the axial histidine imidazole in solution.
      There is an equilibrium between the two heme orientations (A and B), which
      depends on the heme cavity shape, which can be altered by mutation of amino acids
      with side chains (phenyl vs tyrosyl) near the potential position where a heme
      vinyl group would be in one of the isomers. The A:B ratio can be much more
      accurately measured by NMR spectroscopy than by X-ray crystallography.

PMID- 17198428
TI  - Glycine- and sarcosine-based models of vanadate-dependent haloperoxidases in
      sulfoxygenation reactions.
AB  - Reaction of R-styreneoxide with glycine-tert-butylester yielded amino alcohols of
      the general formula NR1R2R3, where R1 = CH2COOtBu and R2 = R3 = 2-phenyl-2
      hydroxyethyl (H2LA); R2 = 2-phenyl-2-hydroxyethyl and R3 = 1-phenyl-2
      hydroxyethyl (H2LB); R2 = H and R3 = 2-phenyl-2-hydroxyethyl (HLC); and R2 = H
      and R3 = 1-phenyl-2-hydroxyethyl (HLD). The corresponding reaction with sarcosine
      tert-butylester and subsequent hydrolysis provided the zwitterion
      +NH(CH3){CH2CHPh(OH)}(CH2CO2-), HLE* (asterisk refers to unprotected
      carboxylate). Reaction of these ligands with VO(OiPr)3 in CH2Cl2 gave the
      oxovanadium(V) complexes [VOL(OiPr)2] and [VOL2(OiPr)] (for LC and LD) or, when
      reacted in the presence of MeOH, [VOL'(OMe)], where L' represents the methyl
      ester of LA, LB, and LE. The crystal and molecular structures of R-HLC, S-HLD,
      R,S-HLE* x H2O, and lambda-[VO(R,S-LB')OMe] have been determined. The complex
      [VOLB'(OMe)] contains vanadium in a distorted trigonal-bipyramidal array (tau =
      0.72), the oxo group in the equatorial plane, and methoxide and N in the apical
      positions, and thus, it structurally models the active center of vanadate
      dependent haloperoxidases. The structure and the bonding parameters, including a
      particularly long d(V-N) of 2.562 A, are backed up by DFT calculations. The
      isolated oxovanadium(V) complexes and the in situ systems L + VO(OiPr)3 catalyze
      the oxidation, by cumylhydroperoxide HO2R', of prochiral sulfides (MeSPh, MeSp
      Tol, PhSBn) to chiral sulfoxides plus some sulfone. The best results with respect
      to enantioselectivity (enantiomeric excess (ee) = 38%) were obtained with the
      system VO(OiPr)3/LA, and the best selectivity with respect to sulfoxide (100%)
      was obtained with [VOLA(OiPr)]. The reaction with the hexacoordinated
      [VO(OMe)(HOMe)LD*] was very slow. Oxidation of PhSBn is faster than that of MeSPh
      and MeSpTol. Turn-over numbers are up to 60 mol of sulfoxide mol-1 of catalyst h
      1 (-20 degrees C). The unspectacular ee apparently is a consequence of
      flexibility of the active catalyst in solution, as shown by the 51V NMR of the
      catalysts [VOL(OR)] and the oxo-peroxo intermediates [VOL(O2R')]. As shown by DFT
      calculations, the peroxo ligand coordinates in the tilted end-on fashion in the
      axial or equatorial position (energy difference = 17.6 kJ/mol).

PMID- 17198429
TI  - Synthesis, crystal structure, and optical properties of LiGd5P2O13, a layered
      lithium gadolinium phosphate containing one-dimensional Li chains.
AB  - A lithium gadolinium phosphate crystal, LiGd5P2O13, has been synthesized by a
      high temperature solution reaction and solved by single-crystal X-ray diffraction
      data. The structure is monoclinic, space group C2/m, with unit cell parameters a
      = 18.645(3), b = 5.6257(5), c = 12.014(2) A, beta = 117.55(6)degrees, V =
      1117.3(3) A3, and Z = 4. LiGd5P2O13 presents a new structural type and is built
      up from [Gd5P2O13]- layers and one-dimensional Li chains with an unusual Li-Li
      distance. The optical properties were investigated in terms of the absorption and
      emission spectra. Additionally, the calculations of band structure, density of
      states, dielectric constants, and refractive indexes were performed with the
      density functional threory method. The obtained results tend to support the
      experimental data.

PMID- 17198430
TI  - Characterization of the crystal and magnetic structures of the mixed-anion
      coordination polymer Cu(HCO2)(NO3)(pyz) {pyz = Pyrazine} by X-ray diffraction, ac
      magnetic susceptibility, dc magnetization, muon-spin relaxation, and spin dimer
      analysis.
AB  - The mixed-anion coordination polymer Cu(HCO2)(NO3)(pyz) was synthesized, its
      crystal structure was determined by X-ray diffraction, and its magnetic structure
      was characterized by ac susceptibility, dc magnetization, muon-spin relaxation,
      and spin dimer analysis. The crystal structure consists of five-coordinate Cu2+
      ions that are connected through syn-anti bridging mu-HCO2- and mu-pyz ligands to
      form a highly corrugated two-dimensional layered network. Bulk magnetic
      measurements show a broad maximum in chi(T) at 6.6 K. The HCO2- and pyz ligands
      mediate ferromagnetic and antiferromagnetic spin exchange interactions between
      adjacent Cu2+ ions with the spin exchange parameters J/kB = 8.17 and -5.4 K,
      respectively (H = -JSigmaSi x Sj). The muon-spin relaxation data show a
      transition to a long-range magnetic ordering below TN = 3.66(3) K. For T < TN,
      the M(H) and chi'ac measurements provide evidence for a field-induced spin-flop
      transition at 15.2 kOe. That Cu(HCO2)(NO3)(pyz) undergoes a long-range magnetic
      ordering is an unexpected result because the one-dimensional Cu(NO3)2(pyz) and
      three-dimensional Cu(HCO2)2(pyz) compounds display linear chain
      antiferromagnetism with no long-range magnetic ordering down to 2 K.

PMID- 17198431
TI  - Supramolecular assemblies of trinuclear triangular copper(II) secondary building
      units through hydrogen bonds. Generation of different metal-organic frameworks,
      valuable catalysts for peroxidative oxidation of alkanes.
AB  - Formation of the trinuclear triangular copper derivative [Cu3(mu3-OH)(mu
      pz)3(EtCOO)2(H2O)] x H2O, 1b (Hpz = pyrazole), has been simply achieved by
      addition of Hpz to a water solution of Cu(EtCOO)2 x H2O and leaving the resulting
      solution to crystallize at ca. 12 degrees C. When the reaction and
      crystallization were carried out at a slightly higher temperature (18-22 degrees
      C), the compound [Cu3(mu3-OH)(mu-pz)3(EtCOO)2(H2O)], 1c, formed. Single-crystal X
      ray molecular structure determinations show that both compounds have analogous
      trinuclear triangular structures, but very different supramolecular assemblies,
      due mainly, but not only, to the crystallization molecule of H2O in 1b. In
      particular, contrarily to the previously reported, strictly related, [Cu3(mu3
      OH)(mu-pz)3(EtCOO)2(EtOH)], 1a, the propionate ions in 1b and 1c do not bridge
      different triangular units, whereas they are involved in intra- and
      intermolecular H-bonds, generating complex supramolecular 2-D MOFs. Compounds 1a
      and 1c act as remarkably active and selective catalysts or catalyst precursors
      for liquid biphasic (MeCN/H2O) peroxidative oxidation of cyclohexane and
      cyclopentane to the corresponding alcohols and ketones.

PMID- 17198432
TI  - Two organically templated niobium and zinconiobium fluorophosphates: low
      temperature hydrothermal syntheses of NbOF(PO4)2(C2H10N2)2 and
      Zn3(NbOF)(PO4)4(C2H10N2)2.
AB  - Two new niobium and zinconiobium fluorophosphates, NbOF(PO4)2(C2H10N2)2 (1) and
      Zn3(NbOF)(PO4)4-(C2H10N2)2 (2), have been prepared under hydrothermal conditions
      using ethylenediamine as a template. The structures were determined by single
      crystal diffraction to be triclinic, space group P1 (No. 2), a = 8.1075 (6) A, b
      = 9.8961 (7) A, c = 10.1420(8) A, alpha = 111.655(1) degrees, beta = 111.51(1)
      degrees, gamma = 93.206(1) degrees, V = 686.19(9) A3, and Z = 2 for 1 and
      orthorhombic, space group Fddd (No. 70), a = 9.1928(2) A, b = 14.2090(10) A, c =
      32.2971 (6) A, V = 4218.66(12) A3, and Z = 8 for 2, respectively. Compound 1 is
      an infinite linear chain consisting of corner-sharing [Nb2P2] 4-MRs bridged at
      the Nb centers with organic amines situated between chains, and compound 2,
      containing the chains similar to that in 1, forms a zeotype framework with
      organic amines situated in the gismondine-type [4684] cavities. The topology of 2
      was previously unknown with vertex symbol 4 x 4 x 4 x 4 x 8 x 8 (vertex 1), 4 x 4
      x 4 x 82 x 8 x 8 (vertex 2), 4 x 4 x 8 x 8 x 82 x 82 (vertex 3), and 4 x 4 x 4 x
      82 x 8 x 8 (vertex 4). The topological relationships between the 4-connected
      network of 2 and several reported (3,4)-connected networks were discussed.

PMID- 17198433
TI  - Dinuclear complexes formed with the triazacyclononane derivative ENOTA4-: high
      pressure 17O NMR evidence of an associative water exchange on
      [MnII2(ENOTA)(H2O)2].
AB  - Mn2+ has five unpaired d-electrons, a long electronic relaxation time, and labile
      water exchange, all of which make it an attractive candidate for contrast agent
      application in medical magnetic resonance imaging. In the quest for stable and
      nonlabile Mn2+ complexes, we explored a novel dimeric triazacyclononane-based
      ligand bearing carboxylate functional groups, H4ENOTA. The protonation constants
      of the ligand and the stability constants of the complexes formed with some
      endogenously important metals (Ca2+, Cu2+, Zn2+), as well as with Mn2+ and Ce3+,
      have been assessed by NMR methods, potentiometry, and UV-vis spectrophotometry.
      Overall, the thermodynamic stability of the complexes is lower as compared to
      that of the corresponding NOTA analogues (H3NOTA, 1,4,7-triaazacyclononane-1,4,7
      triacetic acid). The crystal structure of Mn2(ENOTA)(H2O) x 5H2O contains two six
      coordinated Mn2+, in addition to the three amine nitrogens and the two oxygens
      from the pendent monodentate carboxylate groups, and one water (Mn2) or one
      bridging carboxylate oxygen (Mn1) completes the coordination sphere of the metal
      ion. In an aqueous solution, this bridging carboxylate is replaced by a water
      molecule, as evidenced by the 17O chemical shifts and proton relaxivity data that
      point to monohydration for both metal ions in the dinuclear complex. A variable
      temperature and -pressure 17O NMR study has been performed on [Mn2(ENOTA)(H2O)2]
      to assess the rate and, for the first time on a Mn2+ chelate, also the mechanism
      of the water exchange. The inner sphere water is slightly more labile in
      [Mn2(ENOTA)(H2O)2] (k298ex = 5.5 x 107 s-1) than in the aqua ion (2.1 x 107 s-1,
      Merbach, A. E.; et al. Inorg. Chem. 1980, 19, 3696). The water exchange proceeds
      via an almost limiting associative mechanism, as evidenced by the large negative
      activation volume (deltaV = -10.7 cm3 mol-1). The proton relaxivities measured on
      [Mn2(ENOTA)(H2O)2] show a low-field dispersion at approximately 0.1 MHz arising
      from a contact interaction between the MnII electron spin and the water proton
      nuclear spins.

PMID- 17198434
TI  - Atomic distributions in the gamma-brass structure of the Cu-Zn system: a
      structural and theoretical study.
AB  - The crystal structures, atomic distributions, and theoretical electronic
      structures of five different Cu5-xZn8+x gamma-brass compounds (x = -0.59(3), 
      0.31(3), 0.00(3), 0.44(3), and 0.79(3)) are reported with the goal of identifying
      chemical influences on the observed phase width. These structures have been
      refined by both neutron and X-ray powder diffraction to obtain accurate crystal
      chemical parameters. All compounds crystallize in the space group Iz3m (No. 217)
      (Z = 4), and the unit cell parameters are a = 8.8565(4), 8.8612(5), 8.8664(3),
      8.8745(4), and 8.8829(7) A, respectively, for Cu5.59Zn7.41, Cu5.31Zn7.69,
      Cu5.00Zn8.00, Cu4.56Zn8.44, and Cu4.21Zn8.79. The results indicate specific site
      substitutions on both sides of the ideal composition "Cu5Zn8". In all cases, the
      26-atom cluster building up the -brass structure shows a constant inner [Cu4Zn4]
      tetrahedral star with compositional variation occurring at the outer octahedron
      and cuboctahedron. First principles and semiempirical electronic structure
      calculations using both a COHP and Mulliken population analysis were performed to
      understand the observed compositional range and to address the "coloring problem"
      for the site preferences of Cu and Zn atoms for this series of compounds.

PMID- 17198435
TI  - Anion partitioning and ion-pairing behavior of anions in the extraction of cesium
      salts by 4,5' '-Bis(tert-octylbenzo)dibenzo-24-crown-8 in 1,2-dichloroethane.
AB  - A systematic study of anion partitioning and ion pairing was performed for an
      extraction of individual cesium salts into 1,2-dichloroethane (1,2-DCE) using
      4,5' '-bis(tert-octylbenzo)dibenzo-24-crown-8 as the cesium receptor. Equilibrium
      constants corresponding to the extraction of ion pairs and dissociated ions,
      formation of the 1:1 cesium/crown complex (confirmed by electrospray mass
      spectrometry), and dissociation of the ion pairs in water-saturated 1,2-DCE at 25
      degrees C were obtained from equilibrium modeling using the SXLSQI program. The
      standard Gibbs energy of partitioning between water and water-saturated 1,2-DCE
      was determined for picrate, permanganate, trifluoromethanesulfonate,
      methanesulfonate, trifluoroacetate, and acetate anions. The dissociation of the
      organic-phase complex ion pair [Cs(4,4' '-bis(tert-octylbenzo)dibenzo-24-crown
      8]+NO3- observed in the extraction experiments was shown to be consistent with
      the dissociation constant determined independently by conductance measurements.
      As attributed to the large effective radius of the complex cation, the evident
      anion discrimination due to ion pairing in the 1,2-DCE phase was relatively
      small, by comparison only a tenth of the discrimination exhibited by the anion
      partitioning. Only chloride and picrate exhibit evidence for significantly
      greater-than-expected ion-pairing tendency. These results provide insight into
      the inclusion properties of the clefts formed by opposing arene rings of the
      crown ether upon encapsulation of the Cs+ ion, whose weak anion recognition
      likely reflects the preferential inclusion of 1,2-DCE molecules in the clefts.
      Observed anion extraction selectivity in this system, which may be ascribed
      predominantly to solvent-induced Hofmeister bias selectivity toward large charge
      diffuse anions, was nearly the same whether cesium salts were extracted as
      dissociated ions or ion pairs.

PMID- 17198436
TI  - Substituent effects on exchange coupling: 5-Aryl-substituted semiquinones and
      their complexes with MnII and CuII.
AB  - A series of functionalized radical anion semiquinone (SQ-Ar) ligands and their
      MnII- and CuIIhydro-tris(3-cumenyl-5-methylpyrazolyl)borate (TpCum,MeMII)
      complexes were prepared and characterized. The semiquinone ligands have
      substituted phenyl rings (Ar = -C6H5NO2, -C6H5OMe, -C6H5-tert-Bu, etc.) attached
      to the SQ 5-position. Despite the "remoteness" of the phenyl ring substituents,
      the MII-SQ exchange parameters, J, were found to vary nearly 3-fold. Attempts to
      quantify the substituent effects on J are complicated by the fact that not all
      complexes could be structurally characterized. As such, substituent effects and
      phenyl-ring torsion angles could conspire to produce the observed variation in J
      values. Although there is no clear trend in the J values as a function of SQ
      substituent for the MnII complexes, for the CuII complexes, electron-withdrawing
      substituents on the phenyl ring have greater ferromagnetic J values than the CuII
      complexes of SQ ligands with electron-donating substituents. This trend suggests
      a FM contribution from MLCT excited states in the copper complexes.

PMID- 17198437
TI  - Inorganic-organic framework structures; M(II) ethylenediphosphonates (M = Co, Ni,
      Mn) and a Mn(II) ethylenediphosphonato-phenanthroline.
AB  - The reaction of nickel, cobalt, and manganese with 1,2-ethylenediphosphonic acid
      or 1,2-ethylenediphosphonic acid and 1,10-phenanthroline under hydrothermal
      conditions resulted in the pillared layered structures Co2(H2O)2(O3PC2H4PO3) (I)
      and Ni2(H2O)2(O3PC2H4PO3) (II), which are isostructural to a zinc phase that has
      previously been characterized by X-ray powder methods. In addition, a 1D chain
      structure, Mn(HO3P(CH2)2PO3H)(H2O)2(C12H8N2) (III), and a pillared layered
      structure, Mn(HO3P(CH2)2PO3H) (IV), were obtained. The structures of these phases
      were solved by single-crystal X-ray diffraction methods. The crystallographic
      data are as follows: compound I P21/n (No. 14), a = 5.6500(11) A, b = 4.7800(10)
      A, c = 15.330(3) A, beta = 98.50(3) degrees, V = 409.47(14) A3, Z = 2; compound
      II P21/n (No. 14), a = 5.5807(11) A, b = 4.7205(9) A, c = 15.250(3) A, beta =
      98.55(3) degrees, V = 397.28(13) A3, Z = 2; compound III C2/c (No. 15), a =
      12.109(2) A, b = 15.328(3) A, c = 9.848(2) A, beta = 108.88(3) degrees, V =
      1729.5(6) A3, Z = 4; compound IV P (No. 2), a = 5.498(5) A, b = 7.715(6) A, c =
      8.093(7) A, alpha = 82.986(12) degrees, beta = 75.565(12) degrees, gamma =
      80.582(12)degrees, V = 326.7(5) A3, Z = 2. Magnetic measurements show
      antiferromagnetic behavior below TN = 7 K for I and 13 K for II.

PMID- 17198438
TI  - Kinetics and mechanism of the comproportionation of hypothiocyanous acid and
      thiocyanate to give thiocyanogen in acidic aqueous solution.
AB  - The kinetics of comproportionation of hypothiocyanous acid (HOSCN) and
      thiocyanate (SCN-) to give thiocyanogen ((SCN)2) in acidic aqueous solutions have
      been determined by double-mixing stopped-flow UV spectroscopy. Hypothiocyanite
      (OSCN-) was generated at pH 13 by oxidation of excess SCN- with hypobromite (OBr
      ), followed by a pH jump to acidic conditions ([H+] = 0.20-0.46 M). The observed
      pseudo-first-order rate constants exhibit first-order dependencies on [H+] and
      [SCN-] with overall third-order kinetics. The corresponding kinetics of
      hydrolysis of (SCN)2 have also been examined. Under conditions of high (and
      constant) [H+] and [SCN-], the kinetics exhibit second-order behavior with
      respect to [(SCN)2] and complex inverse dependences on [H+] and [SCN-]. Under
      conditions of low [H+] and [SCN-], the kinetics exhibit first-order behavior with
      respect to [(SCN)2] and independence with respect to [H+] and [SCN-]. We
      attribute this behavior to a shift in the rate-limiting step from
      disproportionation of HOSCN (second-order dependency on [(SCN)2]) to rate
      limiting hydrolysis (first-order dependency on [(SCN)2]). Thus, we have
      determined the following equilibrium constant by the kinetic method: (SCN)2 + H2O
      HOSCN + SCN- + H+; Khyd = [HOSCN][SCN-][H+]/[(SCN)2] = khyd/kcomp = 19.8(+/-0.7)
      s-1/ 5.14(+/-0.07) x 103 M-2 s-1 = 3.9 x 10-3 M2.

PMID- 17198440
TI  - Syntheses, structures, spectroscopy, and chromotropism of new complexes arising
      from the reaction of nickel(II) nitrate with diphenyl(dipyrazolyl)methane.
AB  - The complexes [(dpdpm)Ni(2-NO3)2] (1), [(dpdpm)Ni(2-NO3)(1-NO3)(CH3CN)] (2),
      [(dpdpm)2Ni(1-NO3)(H2O)]NO3 (3), and [(dpdpm)2Ni(H2O)2][NO3]2 (4) (dpdpm =
      diphenyl(dipyrazolyl)methane, Ph2C(C3N2H3)2), have been prepared and
      characterized by IR and UV-vis-NIR spectroscopy and X-ray diffraction studies. X
      ray studies have confirmed that complexes 1-4 all adopt variously distorted
      octahedral structures in the solid state, the largest distortions arising from
      the small bite-angle of the bidentate nitrate ligand in 1 and 2. Magnetic moment
      measurements indicate that these solids are paramagnetic with two unpaired
      electrons. The solution 1H NMR data show that the paramagnetism is maintained in
      solution. Absorption spectra of 1-4 show three main bands in the region of 350
      1000 nm representing spin allowed (d-d) transitions from the ground state 3A2g to
      the excited states 3T2g, 3T1g(3F), and 3T1g(3P). A weak shoulder was also
      detected at about 700-800 nm in most spectra, representing spin-forbidden
      transitions 3A2g 1Eg. A comparison of the crystal field parameters 10Dq and B for
      1-4 to the corresponding values for related complexes indicated that these
      parameters are fairly insensitive to structural variations within this family of
      complexes. The 10Dq/B ratios show greater variations, but no clear correlations
      are apparent between 10Dq/B and such structural features as the nature of ligator
      atoms (N:O ratio), the bonding mode of the nitrate ligand, or the overall charge.
      Complexes 1 (green) and 2 (blue) interconvert as a function of temperature
      (solutions and solid samples), concentration of CH3CN (solutions), or CH3CN vapor
      pressure (solid samples).

PMID- 17198439
TI  - Oxidative N-dealkylation reactions by oxoiron(IV) complexes of nonheme and heme
      ligands.
AB  - Nonheme and heme iron monooxygenases participate in oxidative N-dealkylation
      reactions in nature, and high-valent oxoiron(IV) species have been invoked as
      active oxidants that effect the oxygenation of organic substrates. The present
      study describes the first example of the oxidative N-dealkylation of N,N
      dialkylamines by synthetic nonheme oxoiron(IV) complexes and the reactivity
      comparisons of nonheme and heme oxoiron(IV) complexes. Detailed mechanistic
      studies were performed with various N,N-dialkylaniline substrates such as para
      substituted N,N-dimethylanilines, para-chloro-N-ethyl-N-methylaniline, para
      chloro-N-cyclopropyl-N-isopropylaniline, and deuteriated N,N-dimethylanilines.
      The results of a linear free-energy correlation, inter- and intramolecular
      kinetic isotope effects, and product analysis studied with the mechanistic probes
      demonstrate that the oxidative N-dealkylation reactions by nonheme and heme
      oxoiron(IV) complexes occur via an electron transfer-proton transfer (ET-PT)
      mechanism.

PMID- 17198441
TI  - Modulating the M-M distance in dinuclear complexes. New ligand with a 2,2'
      Biphenol fragment as key unit: synthesis, coordination behavior, and crystal
      structures of Cu(II) and Zn(II) dinuclear complexes.
AB  - The synthesis and characterization of the new polyamino-phenolic ligand 3,3'
      bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2'-dihydroxybiphenyl (L) are reported. L
      contains two diethylenetriamine units linked by a 1,1'-bis(2-phenol) group (BPH)
      on the central nitrogen atom which allows two separate binding amino subunits in
      a noncyclic ligand. The basicity and binding properties of L toward Cu(II) and
      Zn(II) were determined by means of potentiometric measurements in aqueous
      solution (298.1 +/- 0.1 K, I = 0.15 mol dm-3). L behaves as a pentaprotic base
      and as a monoprotic acid under the experimental conditions used, yielding the
      H5L5+ or H-1L- species, respectively. L forms both mono- and dinuclear species
      with both metal ions investigated; the dinuclear species are largely prevalent in
      aqueous solution with a L/M(II) molar ratio of 1:2 at pH higher than 7. L shows
      different behavior in Cu(II) and Zn(II) binding, affecting the dinuclear species
      formed and the distance between the two coordinated metal ions, which is greater
      in the Zn(II) than in the Cu(II) dinuclear species. This difference can be
      attributed to the different degree of protonation of BPH which influences the
      angle between the phenyl rings in the two systems. In this way, it is possible to
      modulate the M(II)-M(II) distance by the choice M(II) and to space the two M(II)
      farther away than was possible with the previously synthesized ligands. L does
      not saturate the coordination sphere of the coordinated M(II) ions in the
      dinuclear species, and thus, these latter species are prone to add guests. 1H and
      13C NMR experiments carried out in aqueous solution, as well as the crystal
      structures of the dinuclear Cu(II) and Zn(II) species formed in aqueous solution,
      aided in elucidating the involvement of L and BPH in Zn(II) and Cu(II)
      stabilization.

PMID- 17198442
TI  - Facile construction of lanthanide metallomacrocycles with the bridging
      imidazolate and triazolate ligands and their ring expansions.
AB  - Four novel tri- or tetranuclear organolanthanide metallomacrocycles [Cp2Ln(mu
      Im)(THF)3 (Cp = C5H5, Ln = Yb (1), Er (2)], [Cp2Dy(mu-Im)]4(THF)]3 x 2THF (3),
      and [Cp'2Yb(mu-eta1:eta2-Tz)]4 x 2THF (Cp' = CH3C5H4) (4) have been synthesized
      through protolysis of Cp3Ln or Cp'3Yb with imidazole or triazole, indicating that
      both the bridge-ligand size and the lanthanide-ion radii can be applied in the
      modulation of the metallomacrocycles. Further investigations on the reactivity of
      complexes 1, 3, and 4 toward phenyl isocyanate reveal that PhNCO inserts readily
      into the simple bridge Ln-N bonds of 1 and 3 to yield the corresponding insertion
      products [Cp2Ln(mu-eta1:eta2-OC(Im)NPh)]3 (Ln = Yb (5), Dy (6)) but cannot insert
      into the Ln-N bond with a mu-eta1:eta2-bonding mode in 4. The novel bridge ligand
      [OC(Im)NPh] can expand the numbers of the ring members from 12 to 18 in 5 or 16
      to 18 in 6. The number of metal atoms in the metallacycles with the ligand
      [OC(Im)NPh] is independent of the lanthanide-ion size; both trinuclear lanthanide
      macrocycles are observed in 5 and 6. All of these new complexes have been
      characterized by elemental analysis and spectroscopic properties, and their
      structures have also been determined through X-ray single-crystal diffraction
      analysis.

PMID- 17198443
TI  - Aluminum and zinc complexes based on an amino-bis(pyrazolyl) ligand: synthesis,
      structures, and use in MMA and lactide polymerization.
AB  - The coordination chemistry of bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine (1, LH)
      with aluminum- and zinc-alkyls has been studied. Reaction of 1 with AlR3 affords
      the adducts [LH] x AlR3 (R = Me, 2; Et, 3), which undergo alkane elimination upon
      heating to yield the amido complexes [L]AlR2 (R = Me, 4; Et, 5). Reaction of
      LiO(iPrO)C=CMe2 with 2 proceeds via N-H deprotonation to give Li[L]AlMe3 (6),
      while the former enolate adds to 4 to generate [Me2C=C(OiPr)OLi] x [L]AlMe2 (7).
      Similarly, the 1:1 reaction of ZnEt2 with 1 gives [LH] x ZnEt2 (9), which is
      transformed into [L]ZnEt (10) upon heating. When an excess of ZnEt2 was used in
      the latter reaction, the bimetallic complex [L]ZnEt x ZnEt2 (11) was isolated
      beside 10. Performing the same reaction in the presence of O2 traces yielded
      selectively the dinuclear ethyl-ethoxide complex [L]Zn2Et2(mu-OEt) (12), which
      was alternatively prepared from the reaction of 10 and ZnEt(OEt). Zinc chloride
      complexes [LH] x ZnRCl (R = Et, 13; p-CH3C6H4CH2, 14) and [L]ZnCl (15) were
      prepared in high yields following similar strategies. Ethyl abstraction from 10
      with B(C6F5)3 yields [L]Zn+EtB(C6F5)3- (16). All complexes have been
      characterized by multinuclear nuclear magnetic resonance (NMR), elemental
      analysis, and single-crystal X-ray diffraction studies for four-coordinate Al
      complexes 2, 4, and 6 and Zn complexes 9-12 and 14. Aluminate species 6 and 7
      initiate the polymerization of methyl methacrylate, and the monomer conversions
      are improved in the presence of neutral complexes 2 or 4, respectively; however,
      these methyl methacrylate (MMA) polymerizations are uncontrolled. Polymerization
      of rac-lactide takes place at 20 degrees C in the presence of zinc ethoxide
      complex 12 to yield atactic polymers with controlled molecular masses and
      relatively narrow polydispersities.

PMID- 17198444
TI  - Negative differential resistance and memory effect in diodes based on 1,4
      dibenzyl C60 and zinc phthalocyanine doped polystyrene hybrid material.
AB  - Negative differential resistance (NDR) and memory effect were observed in diodes
      based on 1,4-dibenzyl C60 (DBC) and zinc phthalocyanine doped polystyrene hybrid
      material. Certain negative starting sweeping voltages led to a reproducible NDR,
      making the hybrid material a promising candidate in memory devices. It was found
      that the introduction of DBC enhanced the ON/OFF current ratio and significantly
      improved the memory stability. The ON/OFF current ratio was up to 2 orders of
      magnitude. The write-read-erase-reread cycles were more than 106, and the
      retention time reached 10,000 s without current degradation.

PMID- 17198445
TI  - Pulse versus oral methylprednisolone therapy in pemphigus vulgaris.
AB  - BACKGROUND: Although corticosteroids have dramatically altered the prognosis of
      patients with pemphigus vulgaris, morbidity and mortality from systemic
      corticosteroid side-effects remains high. High-dose intravenous
      methylprednisolone has been used successfully in blistering diseases to avoid the
      complications of long-term orally-administered glucocorticoids. The objective of
      this study was to compare the effectiveness and side-effects of oral and pulse
      steroid therapy in the treatment of pemphigus vulgaris. METHODS: One hundred and
      twenty-three patients with pemphigus vulgaris were categorized into two groups of
      study and control according to the disease severity and patient's preferred
      method of treatment. The study group included 36 males and 36 females. The
      control group included 26 males and 25 females. The mean +/- SD age of the two
      groups was 42.6 +/- 11.9 and 46.9 +/- 12.8 years, respectively. The mean +/- SD
      duration of the disease was 6.8 +/- 1.1 months in new cases (n = 45) and 25.9 +/-
      26.0 months overally in the study group; it was 7.2 +/- 1.8 months in new cases
      (n = 30) and 28.4 +/- 24.6 months overally in the control group. During the
      induction phase, we performed pulse therapy with methylprednisolone in three
      consecutive monthly courses. Each course included 1000 mg intravenous
      methylprednisolone for 4 days plus 500 mg intravenous cyclophosphamide for 1 day.
      In this phase, the control group received 1 - 2 mg/kg/day oral prednisolone for
      28 days plus 1.5 mg/kg/day azathioprine. All patients were followed for at least
      12 months during which period, clinical response, relapse rate, and side-effects
      were evaluated. RESULTS: Pulse intravenous methylprednisolone with
      cyclophosphamide was generally safe and well-tolerated. Therapeutic responses of
      skin and mucosal lesions, rates of complete remission and relapse, and major
      organ-specific complications were similar in both groups. Significant statistical
      differences existed in total orally-administered prednisolone in one year,
      admission duration, and annual weight increments between the two groups (P <
      0.05). CONCLUSION: Considering the side-effects of long-term oral steroids,
      hazards of obesity, and complications of long-term hospitalization, pulse
      methylprednisolone could be considered in patients who have problems with long
      term admissions or with high-dose oral steroid usage, and also in obese patients.

PMID- 17198446
TI  - Clinical presentation and etiologic factors of hirsutism in premenopausal Iranian
      women.
AB  - BACKGROUND: Hirsutism is a common clinical condition with different etiologies.
      Many of these patients have frank or subclinical abnormalities in the adrenal and
      ovarian steroidogenesis. The disease may be associated with other clinical signs
      of hyperandrogenism. The objective of this study was to investigate the clinical
      features of hirsutism and its etiologic factors in premenopausal Iranian women.
      METHODS: In a cross-sectional study, 790 consecutive premenopausal women referred
      to the dermatology Clinics of Hazrat-e Rasool and Firoozgar University Hospitals
      and three private dermatology clinics during 2001 - 2003 with the clinical
      diagnosis of hirsutism were studied. All patients underwent detailed clinical
      assessment and transabdominal ultrasonography of the ovaries. Endocrinologic work
      up was performed for 285 patients. RESULTS: Hirsutism was mild in 65%, moderate
      in 32.5%, and severe in 2.5% of the patients. Positive family history was found
      in 56.2%. Hormonal studies revealed some abnormalities in 35.2% of the patients.
      Coexisting medical conditions included acne in 70% of the patients, menstrual
      irregularity in 38.6%, androgenic alopecia in 21.3%, obesity in 6.5%, acanthosis
      nigricans in 4.9%, and diabetes in 0.6% of the patients. Etiology of hirsutism
      was identified as polycystic ovary syndrome (62.53%), idiopathic (35.19%),
      congenital adrenal hyperplasia (0.38%), prolactinoma (0.13%), and undetermined
      (1.77%). Polycystic ovary syndrome was diagnosed more frequently in women with
      menstrual irregularity than eumenorrheic patients (97.70% vs. 40.41%, P < 0.001).
      CONCLUSIONS: Hirsute patients frequently have either elevated androgen levels or
      clinical conditions associated with hyperandrogenemia. Eumenorrhea does not rule
      out endocrine abnormality and particularly polycystic ovary syndrome which is a
      common cause of hirsutism. We recommend performing endocrinologic work up,
      investigation of coexisting hyperandrogenic states, and evaluation of polycystic
      ovary syndrome in all patients with hirsutism.

PMID- 17198447
TI  - Therapeutic effect of macular grid photocoagulation in treatment of nonexudative
      age-related macular degeneration.
AB  - BACKGROUND: To investigate the effect of prophylactic subthreshold laser macular
      grid photocoagulation on drusen area and to evaluate the visual outcome and
      incidence of choroidal neovascularization in patients with soft drusen
      maculopathy. METHODS: In a nonrandomized nonmasked clinical trial, 18 patients
      (36 eyes) with bilateral soft drusen maculopathy were studied. For each patient,
      one eye was treated with 48 subthreshold (invisible end-point) applications of
      532-nm KTP-laser in a macular grid pattern and the fellow eye was observed. Soft
      drusen areas were calculated and compared between the two groups at baseline and
      follow-up visits at 3, 6, 12, and 30 months of therapy. Best corrected visual
      acuity was also compared in observed and laser-treated eyes. Reduction of drusen
      area, change in visual acuity, and rate of CNV were assessed in both groups.
      RESULTS: At baseline, there was no significant difference in the mean drusen
      surface area between the two groups (P = 0.90). The mean surface area of soft
      drusen in treated eyes was 6.51 mm(2) after 30 months and 7.58 mm(2) (P = 0.50)
      in the control eyes. There was a trend towards reduction in the mean soft drusen
      area after 30 months from baseline in laser-treated eyes (6.51 vs. 6.97 mm(2)).
      In treated eyes, there was no statistically significant difference between the
      mean best corrected visual acuity at the baseline (0.28 logMAR) and after 30
      months (0.32 logMAR) (P = 0.40). CONCLUSION: Subthreshold macular grid
      photocoagulation with 532-nm KTP-laser did not seem to reduce drusen surface area
      significantly and did not improve best corrected visual acuity after 30 months.
      No exudative lesion developed in laser-treated eyes.

PMID- 17198448
TI  - Consequence of body packing of illicit drugs.
AB  - BACKGROUND: During the last decade, increased rates of drug traffic have led the
      smugglers to use various methods. One of these methods of illicit drug smuggling
      is body packing. Smuggling by intra-abdominal concealment is called "body
      packing". In this research, mortality rate was investigated due to body packing
      in Tehran. METHODS: A descriptive study (case series) was designed on all corpses
      referred to the Forensic Medicine Organization of Tehran between April 1999 -
      December 2000. Demographic data such as sex, age, marital status, addiction, job,
      education level, type of opioid and the weight, number of packets, and results of
      blood and urine morphine tests by thin-layer chromatographic method were
      investigated. RESULTS: Continental system of law is used in Iran and 0.06% of the
      referred corpses to Forensic Medicine Organization of Tehran were body packers.
      There were 12 cases, all of them were men. The mean age of body packers was 43
      years (range 20 - 62). The minimum weight of the packets was 20 g and the maximum
      weight was 1400 g (mean = 501 g). The minimum number of the packets was one and
      the maximum number of the packets was 48. Twenty five percent of the corps were
      putrefied and one corpse was mummified. None of the body packers had academic
      education nor were employed. Nine of them lived in cities. Twenty five percent of
      them were intravenous addicts. The corpses were found mostly in terminals (17%),
      roads (58%), and cities (25%). CONCLUSION: Hospital physicians may neglect this
      type of gastrointestinal foreign body if they are not aware of the body packer
      syndrome. Body packing should be suspected in anyone with signs of drug-induced
      toxic effects after a recent arrival on city terminals or when there is no
      history of recreational drug use.

PMID- 17198449
TI  - Q-angle: an invaluable parameter for evaluation of anterior knee pain.
AB  - BACKGROUND: Patellofemoral pain syndrome is a descriptive term applied to
      patients with nonspecific anterior knee pain, and is the most common knee
      problem. The pain in most patellofemoral disorders is generalized to the anterior
      part of the knee. One important concept in patellofemoral joint function is the
      quadriceps angle (Q-angle). Theoretically, a higher Q-angle increases the lateral
      pull of the quadriceps femoris muscle on the patella and potentiates
      patellofemoral disorders. This study was undertaken to evaluate the relationship
      between the anterior knee pain and Q-angle. METHODS: This prospective study was
      performed on two groups; the case group consisted of 100 outpatients (44 men, and
      56 women) aged between 15 and 35 years, with anterior knee pain. The control
      group consisted of 100 outpatients (50 men, and 50 women) with the same age
      distribution, who presented with different problems in the upper extremities and
      no knee problems. The Q-angle of each knee was measured in all participants,
      using a universal goniometer. RESULTS: The mean Q-angle for men, women, and all
      participants in the case group was 15.2, 20.1, and 18.0 degrees, respectively. In
      the normal control group the angles were 12.1, 16.7, and 14.9 degrees,
      respectively. All these differences were statistically significant (P < 0.001).
      CONCLUSION: These results substantiate the fact that patients with anterior knee
      pain have larger Q-angles than healthy individuals.

PMID- 17198450
TI  - Prognostic values of proliferative markers ki-67 and repp86 in breast cancer.
AB  - BACKGROUND: Breast cancer is the leading cause of carcinoma death in women.
      Proper treatment depends on the consideration of molecular biology status of
      tumor cells, which may determine the patient's treatment and prognosis. To
      determine the prognostic models for this disease, we evaluated the role of cell
      proliferation-related antigens including ki-67 (a nuclear antigen, expressed in
      G1, G2, and M phases of cell cycle) and repp86 (an 86-kDa nuclear protein
      expressed in S, G2, and M phases of cell cycle) for detection of biologic
      behavior of breast cancer. METHODS: We studied 60 women with grade I and II lymph
      node-negative and 27 with grade III lymph node-positive breast cancers. The mean
      follow-up periods for these two groups were 60 and 72 months, respectively. Tumor
      cell proliferation was measured by immunohistochemical methods with monoclonal
      antibodies directed against the nuclear antigens ki-67 and repp86. RESULTS: The
      ki-67, repp86 labeling indices (percentage of antibody-stained tumor cell nuclei)
      were not statistically different between the cases and controls of lymph node
      negative patients (ki-67 with P = 0.33; repp86 with P = 0.40). The odds ratio
      (the mean chance of ki-67 labeling index > 10%, repp86 labeling index >10%) in
      patients with recurrence was 4 (CI = 0.2 - 76.5) for ki-67 and 3.6 (CI = 0.4 -
      32.5) for repp86. Both indices were statistically different in lymph node
      positive cases and controls (P < 0.0001). The odds ratio in patients with
      recurrence was 87 (CI = 4 - 18.71) for ki-67 and 71.5 (CI = 5.7 - 899.2) for
      repp86. CONCLUSION: The present study confirms the importance of cell
      proliferation as a determinant of biologic behavior of breast cancer. Measurement
      of ki-67 and repp86 labeling indices may be very helpful for physicians to detect
      high-risk patients and to adopt appropriate procedure such as adjuvant therapy.

PMID- 17198451
TI  - Survival rate of gastric and esophageal cancers in Ardabil province, North-West
      of Iran.
AB  - BACKGROUND: Upper gastrointestinal cancer is the most common cancer in Ardabil
      Province, North-West of Iran, accounting for more than 50% of all cancer deaths
      in this area. We conducted this study to determine the present survival rate of
      patients with esophageal and gastric cancers before launching interventional
      studies. METHODS: A prospective follow-up study of 420 biopsy-proven patients
      (127 females, mean age: 64) with upper gastrointestinal cancer (141 esophageal
      and 279 stomach cancers) who were initially diagnosed in Aras Clinic, the main
      gastrointestinal referral center of Ardabil Province, from 2000 through 2004, was
      performed with collection of data on demographics, tumor characteristics,
      pathologic stage, treatment methods, complications, survival time, etc. Data were
      gathered through direct interview with patients or their families in 303 cases
      and evaluation of death certificates in 55 patients. Follow-up was from cancer
      diagnosis until death, or immigration. Survival according to stage of disease,
      Lauren tumor type, tumor location, surgery, and adjuvant chemotherapy was
      analyzed, and results were compared with those of western series. RESULTS: Sixty
      two cases were lost to follow-up. The one- and five-year survival rates in the
      patients with upper gastrointestinal cancer in Ardabil Province were 40.5%, and
      0.8%, respectively. In the univariate analysis, men had a slightly lower survival
      rate than women (P = 0.21) and patients with esophageal cancer had a longer
      survival rate compared to stomach cancer patients (P = 0.15). Patients who had
      undergone surgery (P < 0.001) and/or chemotherapy (P < 0.001) survived longer
      than those without such treatments. Tumor morphology, age at diagnosis,
      radiotherapy, alcohol, and opium consumption did not show any significant effects
      on the survival rate of patients. In multivariate analysis, only smoking was
      remained as an independent factor for stomach cancer (P = 0.04) while in
      esophageal cancer, surgery and grade of differentiation were significant
      predictors of survival. CONCLUSION: Survival rate of stomach and esophagus cancer
      cases in Ardabil is relatively low. Intervention for early detection and therapy
      is necessary to increase survival.

PMID- 17198452
TI  - Expression of p53 in colorectal carcinoma: correlation with clinicopathologic
      features.
AB  - BACKGROUND: The p53 gene mutation is closely related to carcinogenesis in most
      malignant diseases. The main function of wild p53 protein is to maintain the
      integrity of genes by detecting mutations and preventing the division of cells
      with damaged DNA. The mutated form of p53 protein is overexpressed due to an
      extended half-life and can be easily detected by immunohistochemistry. OBJECTIVE:
      To estimate the frequency of p53 protein overexpression in colorectal carcinoma
      and its correlation with some clinicopathologic variables. METHODS: One hundred
      paraffin-preserved colorectal carcinoma samples were collected randomly from
      patients undergoing tumor resection from April 1995 through April 2001 in Omid
      Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran.
      The overexpression of p53 protein was studied using a monoclonal antibody (clone
      DO-7; Dako). The number of cells stained were classified semiquantitatively as (
      ): <5% positive cells, (+): 5 - 25% positive cells, (++): 25 - 75% positive
      cells, and (+++): >75% positive cells. Clinicopathologic data including gender,
      age, tumor location, histologic type, and stage (Astler-Coller) were collected
      from the files maintained at the Department of Pathology. The correlation between
      p53 protein overexpression and each variable was evaluated using Chi-square
      analysis. RESULTS: p53 staining was positive in 59 of 100 specimens. Out of these
      100 specimens, 16 were weekly (+), 16 moderately (++), and 27 intensely (+++)
      positive for p53 protein over-expression. There was no significant correlation
      between p53 staining and gender (P = 0.34), age (< 40 vs. > or = 40 yr; P =
      0.74), site of tumor (right vs. left colon and rectum; P = 0.26), pathologic type
      (mucinous vs. nonmucinous; P = 0.63), and stage of the disease (P = 0.12).
      CONCLUSION: Considering the p53 protein overexpression in a relatively high
      percentage of patients, it seems that p53 mutation plays an important role in
      development of colorectal carcinoma. There was no significant association between
      p53 protein expression and some common clinicopathologic variables such as age,
      gender, site of tumor, pathologic type, and stage of the disease.

PMID- 17198453
TI  - Comparison of microtia reconstructive surgery with autograft versus homograft.
AB  - BACKGROUND: Microtia is a congenital abnormality with low incidence but
      considerable morbidities. Reconstruction of the microtia deformity is a complex
      and difficult process that requires a proper planning. The primary technique of
      reconstruction employs patient's own rib cartilage. Irradiated homograft
      cartilages previously have been used in facial reconstruction but its application
      in microtia surgery has not been reported yet. This study is designed to compare
      the results of autograft versus homograft auriculoplasty. METHODS: Between 1992 -
      2002, 23 patients underwent auricular reconstructive surgery by the senior author
      in our department. Autograft implantation was performed in one stage but
      homograft auriculoplasty was done in two stages. RESULTS: Auricular deformity was
      right-sided in 13, left-sided in 8, and bilateral in 2 cases. Implanted graft was
      autograft in 9 patients and homograft in 14 patients. During mean follow-up of 4
      years, cartilage graft resorption was detected in two cases, one in autograft and
      one in homograft group (P > 0.05). No postoperative infection was observed.
      Status of postauricular sulcus was optimal in 85.7% of homograft and 77.8% of
      autograft groups (P > 0.05). The satisfaction score of the patients and/or
      parents was excellent in 66.7% of autograft and 92.9% of homograft groups (P <
      0.01). CONCLUSION: Based on better satisfaction score, equivalent aesthetic
      appearance, and absence of complications such as scaring and pain on the chest
      wall, homograft auriculoplasty is an appropriate option for reconstructive
      surgery in patients with microtia.

PMID- 17198454
TI  - Inter- and intra-observer variability of the Los Angeles classification: a
      reassessment.
AB  - BACKGROUND: Los Angeles classification is widely adopted for reporting endoscopic
      gastroesophageal reflux disease. We assessed the inter- and intra-observer
      variability of the Los Angeles classification. METHODS: Still images (n = 254) of
      the lower esophagus were presented to 9 gastroenterologists (6 experts and 3
      trainees) and they were asked to report the images according to the Los Angeles
      classification. After 2 weeks the images were reordered and they were asked to
      report them again. Kappa statistic was calculated for intra- and inter-observer
      variability. RESULTS: The kappa for intra-observer agreement was 0.54
      (attendings: 0.54; trainees; 0.55; P = not significant) and the inter-observer
      agreement was 0.22 (attendings: 0.20; trainees: 0.31; P = 0.027). The inter- and
      intra-observer kappa values in differentiating nonerosive from erosive cases were
      0.22 (attendings: 0.21; trainees: 0.31, P = not significant) and 0.57
      (attendings: 0.58; trainees: 0.55, P = not significant), respectively.
      CONCLUSION: According to our data, the Los Angeles classification has acceptable
      intra-observer variability, both for detecting presence or absence of erosions
      and for differentiating between different degrees of esophagitis, while its inter
      observer performance seems to be less acceptable. It may be reasonable and timely
      to have another look at the Los Angeles classification to see whether its
      performance can be improved even further.

PMID- 17198455
TI  - Dendritic spine changes in medial prefrontal cortex of male diabetic rats using
      Golgi-impregnation method.
AB  - BACKGROUND: Neuropathy is one of the major complications contributing to
      morbidity in patients with diabetes mellitus. The effect of diabetes on brain has
      not been studied so much and no gross abnormality has been found in the central
      nervous system of patients with diabetic neuropathy. This study was conducted to
      evaluate the time-dependent structural changes in medial prefrontal cortex of
      male diabetic rats using Golgi-impregnation method. METHODS: Male Wistar rats
      were randomly divided into the control and diabetic groups. For induction of
      diabetes, a single dose of streptozotocin (60 mg/kg) was injected
      intraperitoneally. At the end of the first and second months, the rats were
      transcardially perfused with a solution of phosphate buffer containing
      paraformaldehyde and Golgi-impregnated method was used to evaluate the changes of
      dendritic spines in medial prefrontal cortex. RESULTS: There was a significant
      reduction in the mean density of pyramidal neuron dendritic spines in the layers
      II and III of medial prefrontal cortex only after 2 months in the diabetic group
      compared to age-matched controls (P < 0.05). CONCLUSION: Diabetes induces a
      reduction in the spine density of apical dendrites of medial prefrontal cortex
      only in two-month diabetic rats.

PMID- 17198456
TI  - Mitoxantrone reduced disability in Iranian patients with multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis is a leading cause of disability in young adults.
      Mitoxantrone has recently been shown to be effective in ameliorating multiple
      sclerosis activity and reducing the relapse rate. This study aimed to assess the
      efficacy of mitoxantrone on disease activity and decreasing relapse rate in
      patients with multiple sclerosis in Iran. METHODS: This was a clinical trial on
      patients who received intravenous mitoxantrone, 12 mg/m2 every 3 months. The
      study was performed at Isfahan Multiple Sclerosis Clinics, affiliated to Isfahan
      University of Medical Sciences. This clinical trial was conducted from October
      2003 through April 2005. One hundred and forty-seven patients with worsening
      relapsing-remitting and secondary progressive multiple sclerosis received
      mitoxantrone, 12 mg/m(2) every 3 months. Clinical assessment was made every 3
      months for one year. RESULTS: Of the 147 patients, 129 (93 females and 36 males)
      could successfully complete the course of our study. A significant therapeutic
      effect (P < 0.0001) was detected for the attack rate before and after treatment.
      The Mean attack rate 12 months before treatment was 1.10 (SD = 0.95), which
      reduced to 0.09 (SD = 0.29) during treatment. The Mean expanded disability status
      scale at the beginning of the treatment was 4.32, which declined to 3.62 (P <
      0.0001) after one year. CONCLUSION: Mitoxantrone was generally well tolerated and
      reduced progression of disability and clinical exacerbation in our patients.
      Physicians must be careful about the complications of mitoxantrone especially
      cardiotoxicity.

PMID- 17198457
TI  - Wilms' tumor: a 10 year retrospective study.
AB  - BACKGROUND: Wilms' tumor (nephroblastoma) is the most common renal malignancy of
      childhood. The aim of the study was to evaluate the characteristics of Wilms'
      tumor and the results of combined modality treatment obtained in our center in
      Tehran. METHODS: Fifty-five patients diagnosed as having Wilms' tumor were
      studied in the period between February 1992 and March 2002. Demographic features,
      mode of presentation, associated anomalies, the stage of tumor, histopathologic
      results, and the survival rates were evaluated. RESULTS: Of these 55 patients, 31
      were males and 24 were females (M/F = 1.2). The mean age at the time of diagnosis
      was 45.2 months. The distribution of 54 operated patients according to the
      surgical stage was: stage I 32.7%, stage II 16.36%, stage III 38.1%, stage IV 9%,
      and stage V 1.8% (one patient (1.8%) has not been operated). Favorable histology
      was diagnosed in 54.5% and unfavorable histology in 43.6% of the patients. The
      patients were treated according to National Wilms' Tumor Study protocols. The
      relapse-free and overall 4 years survival rates were 71% and 86%, respectively.
      CONCLUSION: As a developing country, with similar relapse free and overall
      survival rates to National Wilms' Tumor Study, our institution showed an
      improvement in the treatment of patients with Wilms' tumor in recent 10 years,
      but with more adaptation to the National Wilms' Tumor Study treatment protocols
      better optimum results seem to be achievable.

PMID- 17198458
TI  - Esophageal cancer in Northeastern Iran: a review.
AB  - Golestan Province in northeastern Iran has one of the highest rates of esophageal
      squamous cell cancer in the world. This article reviews the studies conducted on
      esophageal squamous cell cancer in this area and summarizes the data on
      epidemiologic patterns, incidence trends, and etiology of esophageal squamous
      cell cancer in this province.

PMID- 17198459
TI  - Iranian national diabetes research network project: background, mission, and
      outcomes.

PMID- 17198460
TI  - Radiologic findings in seven patients with fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva is a rare and disabling syndrome, which is
      characterized by heterotopic ossifications and skeletal deformities. So far,
      around 200 patients with fibrodysplasia ossificans progressiva have been reported
      in the world literature. Herein, we analyze the clinical records of 7 known cases
      of fibrodysplasia ossificans progressiva from Iran who were admitted to the
      pediatrics wards of our centers between 1983 and 2002, and present the radiologic
      findings.

PMID- 17198461
TI  - Extramedullary plasmacytoma of the gingiva.
AB  - Extramedullary plasmacytoma is defined as neoplastic proliferation of plasma
      cells in soft tissue. It accounts for up to 3% of all plasma cell tumors.
      Approximately, 90% of extramedullary plasmacytomas are found in the head and neck
      region commonly affecting the nasal cavity, paranasal sinuses, tonsillar fossa,
      and oral cavity. Radiotherapy is the common modality of treatment with or without
      adjuvant chemotherapy. We report a case of extramedullary plasmacytoma of the
      gingiva.

PMID- 17198462
TI  - Carcinoid tumor of lung with Cushing's syndrome.
AB  - Carcinoid tumor of lung with Cushing's syndrome is a rare condition. We report a
      38-year-old man, with a 28-month history of Cushing's syndrome presented with
      hypertension, diabetes mellitus, decreased libido, muscle weakness and
      fatigability, moon facies, buffalo hump, truncal obesity, cutaneous striae, and
      easy bruisability. Diagnosis was made by measurements of ACTH (149 pg/mL) and
      cortisol levels (36 microg/dL) and computerized tomography of the chest.

PMID- 17198463
TI  - Benign metastasizing leiomyoma of the uterus.
AB  - Herein, we report on a well-characterized benign metastasizing leiomyoma,
      presented in an unusual site. Up to the knowledge of authors, so far, only 76
      cases of benign metastasizing leiomyoma have been reported. The tumor presented
      as a retroperitoneal mass three years after a hysterectomy Performed for
      leiomyomatosis of the uterus with extensive areas of hyalinization.
      Histopathologic and immunohistochemical studies of the resected mass were similar
      to the uterine leiomyoma, showing moderate cellularity of bland looking smooth
      muscle cells with minimal atypia, inconspicuous mitosis, and no necrosis in a
      hyalinized background.

PMID- 17198464
TI  - A fibrous histiocytoma of intermediate malignancy arisen from the parotid gland.
AB  - The light microscopic and immunohistochemical characteristics of a case of
      fibrous histiocytoma of intermediate malignancy arising from the parotid gland
      are presented. This neoplasm is rare in this site and must be distinguished from
      other spindle cell tumors of the parotid gland, particularly those of epithelial
      and myoepithelial origins. Histologic characteristics similar to those displayed
      by dermatofibroma and dermatofibrosarcoma protuberans help to differentiate this
      tumor from other spindle cell tumors. The absence of cytochemical epithelial
      markers is useful for establishing the diagnosis. This tumor appears to have
      arisen from mesenchymal elements within the gland.

PMID- 17198465
TI  - Primary subacute osteomyelitis of the greater trochanter.
AB  - Primary subacute osteomyelitis is difficult to diagnose, because of its insidious
      onset, mild symptoms, lack of a systemic reaction, and similarity with tumoral
      conditions. This condition is seen mostly in the epiphysis or metaphysis of
      tibia. Although it has been reported at various bones, its occurrence in the
      greater trochanter is rare. We describe two patients, 4 and 14 years old, with
      mild pain of the hip joint and limping without history of acute bone infection.
      Radiography showed a lytic lesion in the greater trochanter resembling Brodie
      abscess. Both patients were treated completely with antibiotics.

PMID- 17198466
TI  - Acquired hemophilia as a cause of primary postpartum hemorrhage.
AB  - A 32-year-old primigravid woman developed acquired factor VIII inhibitor after
      delivery. She presented with postpartum hemorrhage and large hematoma in
      episiotomy site. Laboratory examinations showed markedly prolonged activated
      partial thromboplastin time, low levels of factor VIII (8%), and factor VIII
      inhibitor (2 Bethesda units). The bleeding was controlled successfully using
      combined treatment with factor VIII, intravenous immunoglobulin, steroids, and
      recombinant factor VIIa. Six months after delivery, factor VIII inhibitor was not
      present and factor VIII concentration increased to normal range. Acquired
      hemophilia is a life-threatening disorder. Precise screening of coagulation
      factors is essential for diagnosis of persisting postpartum hemorrhage.

PMID- 17198467
TI  - Rh alloimmunization and term delivery.
AB  - Nowadays management of severe Rh alloimmunization consists of serial
      determination of middle cerebral artery peak systolic velocity, amniocentesis,
      cordocentesis, and in many instances intrauterine transfusion. We present a case
      of severe Rh alloimmunization who, for the first time in Iran, was delivered at
      term after several intrauterine transfusions.

PMID- 17198468
TI  - Urolithiasis associated with bilateral pelvic diverticula: a case report.
AB  - We present a case of renal stone associated with bilateral pelvic diverticula.
      The initial diagnosis by ultrasonography and plain abdomen radiography (KUB) was
      urolithiasis with a 15-mm calculus in the right renal pelvis. The patient was
      referred for extracorporeal shock wave lithotripsy, but no stone fragments were
      yielded. So, further evaluations were performed by using repeated
      ultrasonography, intravenous urography, and computerized tomography, which
      revealed the presence of diverticula in both right and left renal pelvises with
      stone fragments within the right sided diverticulum. We concluded that
      intravenous urography and contrast-enhanced computerized tomography are essential
      for confirmation of diagnosis when ultrasonographic findings suggest the presence
      of renal cystic lesions, or when stone fragments are not yielded after
      extracorporeal shock wave lithotripsy.

PMID- 17198469
TI  - Photoclinic. Spontaneous dissection of the abdominal aorta.

PMID- 17198470
TI  - The historical backgrounds of the ministry of health foundation in Iran.
AB  - The early efforts for promotion of public health measures and prevention of fatal
      epidemic diseases in Iran date back to the second half of the 19th century. Based
      on historical records, the informal protosanitary councils had existed since the
      early 1850s, but a new formal health institution called "Sanitary Council", or
      "Majles-e Hefz al-Sehheh" was founded in 1881. Then, it was reestablished as a
      permanent council in 1904. The Sanitary Council was the only major public health
      authority under the auspices of "Ministry of the Interior" up to 1920. Then the
      Ministry of Health and Charity Affairs or "Vezarat-e Sehhyeh va Omuor-e
      Kheiryyeh" was founded in 1920, but it was dissolved in 1921. Between 1921 and
      1941, there was no ministry of public health in Iran and during this period, the
      public health and medical affairs were mananged by the Public Health
      Administration known as Sehhyeh Koll-e Mamlekati that was established in 1926 and
      finally in 1941, the Ministry of Health ( Vezarat-e Behdari) was founded.
      Presented here, is the historical backgrounds of the foundation of the Ministry
      of Health in Iran, as well as the list of the Health Ministers between 1941 and
      1979.

PMID- 17198471
TI  - Publication of the first journal of dentistry in Iran.
AB  - The first scientific journal of dentistry in Iran was published by the "Iranian
      Dentists' Syndicate" (called in Persian "Sandikay-e Dandanpezeshkan-e Iran") in
      1951. A brief account of the journal and its editorial board is presented here.

PMID- 17198472
TI  - Solid-cystic papillary epithelial neoplasm of the pancreas. A diagnostic and
      therapeutic challenge.

PMID- 17198473
TI  - Solid pseudopapillary tumors of the pancreas: diagnosis and curative treatment.
AB  - OBJECTIVES: To highlight an infrequent occurrence using a series of clinical
      cases with symptoms and signs, and specific radiological findings allowing its
      diagnosis and treatment, which is in most cases successful. PATIENTS AND METHODS:
      A descriptive and retrospective study of patients diagnosed by computed
      tomography scanning and then treated with surgery in the Pancreas and Biliary
      Unit of a University Hospital from March 1999 to September 2005. RESULTS: There
      were 6 female patients with a mean age of 33.5 years (range 11-72). Most common
      signs included pain and a palpable mass in the abdomen. Three patients were
      diagnosed by computed tomography scanning, and a differential diagnosis with a
      neuroendocrine tumor was performed for the remaining three subjects. Surgical
      treatment was adapted to each patient according to the findings and images seen
      in their computed tomography scans. Biopsy results confirmed the presumed
      diagnoses, and showed one case of solid pseudopapillary carcinoma of the
      pancreas. Average hospital stay was of 18.16 days (range 8-30). Mortality rate
      was 0%. No recurrences occurred during follow-up for 46.3 months on average
      (range 12-76). CONCLUSIONS: The presence of a huge mass in the pancreas of a
      young female should prompt suspicion for a solid pseudopapillary tumor. Given its
      low malignant potential, and the presence of specific radiographic patterns, its
      diagnosis should be accurate, as radical surgical treatment is effective.

PMID- 17198474
TI  - Prognostic value of flow cytometry in surgically treated primary gastric
      lymphoma.
AB  - AIM: To investigate whether flow cytometry could help to define the optimal
      therapeutic strategy of primary gastric lymphomas. MATERIAL AND METHOD:
      Retrospective study of 46 patients having primary gastric lymphoma--according to
      Dawson criteria--in Ann Arbor stage IE and IIE, who were surgically treated. From
      selected paraffin-embedded tissue blocks of the tumor, DNA content was studied by
      flow cytometry (FC). Other pathological tumor features were analysed by
      hematoxiline-eosine and Giemsa stains as well as immunohistochemical study; any
      possible influence on postoperative survival was investigated through statistical
      analysis. RESULTS: The DNA ploidy pattern was diploid in 40 cases (87%) and
      aneuploid (hyperdiploid) in 6 (13%). Postoperative survival probability (PSP) was
      62.7% at 5 years. Statistical analysis showed significant prognostic value for
      Ann Arbor classification--with higher PSP for stage IE (p = 0.009)--and FC
      parameters: diploid tumors had higher PSP than aneuploid tumors. Also tumors
      having S-phase (p = 0.044) or G2-M phase values (p = 0.023) under the respective
      mean values had higher PSP. No influence on PSP was found for wall invasion,
      Helicobacter pylori infection, Isaacson's histologic type or resection margin
      involvement. No significant relationship was appreciated between Isaacson's
      histologic type and DNA ploidy patterns. CONCLUSION: FC could be useful in
      assessing gastric lymphoma prognosis.

PMID- 17198475
TI  - Preoperative detection of gastrointestinal neuroendocrine tumors using endoscopic
      ultrasonography.
AB  - OBJECTIVE: Almost 30% of gastroenteropancreatic neuroendocrine tumors (GEPET)
      escape preoperative identification using standard imaging techniques. The goal of
      this retrospective study is to present our cumulative experience in the
      assessment of GEPET by preoperative endoscopic ultrasonography (EUS), and to
      compare it with a literature review. PATIENTS AND METHODS: Thirty-seven patients
      with suspected specific hormonal syndromes were sequentially examined with US,
      CT, MRI, angiography, OctreoScan, and radial and sectorial EUS. Sixteen were
      males (43%) and 21 were females (57%), with a mean age of 61 years (interval: 40
      84 a). Of all 37 patients, 27 had 19 endocrine tumors in the pancreas and 14
      tumors in their gastrointestinal tract. No tumors were demonstrated in 10
      patients, hence they were used as a control group. Of all 37 patients, 24 were
      operated on or had histological samples collected, with the presence of 26 GEPET
      (10 carcinoids) being confirmed in 22 patients. RESULTS: EUS sensitivity and
      diagnostic accuracy were 81% and 78%. Specificity was 80%. All these values were
      similar to the mean values obtained from the literature review. Three pancreatic
      rumors smaller than or equal to 1 cm (insulinomas) were detected, which had
      escaped diagnosis with previous US, CT, and MRI studies. An echoendoscopic
      examination of the pancreas could not be completed in two cases (5%), a pancreas
      carcinoid and an already gastrectomized double pancreatic gastrinoma. CONCLUSION:
      EUS is a good preoperative technique for GEPET detection, and may likely be
      superior to other imaging techniques in the assessment of small tumors. The
      usefulness of EUS as a primary exploration after US or HCT has been posited for
      tumor diagnosis and localization before surgery.

PMID- 17198476
TI  - Complete rectal prolapse clinical and functional outcome with Delorme's
      procedure.
AB  - INTRODUCTION: Many surgical techniques -both through the perineal and abdominal
      routes- have been described for the treatment of rectal prolapse. The aim of this
      work is to evaluate the clinical and functional outcome with Delorme's perineal
      procedure. PATIENTS AND METHODS: Twenty-one patients with complete rectal
      prolapse were studied from July 2000 to October 2005. Age, gender, anesthetic
      risk, and accompanying symptoms were all assessed. Diagnostic tests performed
      included: colonoscopy, anorectal manometry before and after surgery, and 360
      masculine endoanal ultrasonography. Delorme's procedures were carried out by only
      one surgical team. RESULTS: No mortality occurred, and morbidity was minimal.
      Prolapse relapse rate was 9.52% with a mean follow-up of 34 months. Anal
      continence improved in 87.5% of patients, and no surgery-associated constipation
      ensued. Mean hospital stay was 2 (range 1-4) days. During the postoperative
      period no pain developed in 17 patients, and 4 patients had mild pain.
      Satisfaction with surgery was high in 16 cases (76.19%), moderate in 3 (14.28%),
      and low in 2 (9.52%). CONCLUSIONS: Delorme's procedure for the management of
      complete rectal prolapse is associated with low morbidity, improves anal
      continence, gives rise to no postsurgical constipation, and has an acceptable
      relapse rate. Patient satisfaction with this procedure is high because of its
      high comfortability (intradural anesthesia, short hospital stay, and little
      postoperative pain) and optimal results.

PMID- 17198477
TI  - Non-alcoholic fatty liver disease. From insulin resistance to mitochondrial
      dysfunction.
AB  - Non-alcoholic fatty liver disease represents a set of liver lesions similar to
      those induced by alcohol that develop in individuals with no alcohol abuse. When
      lesions consist of fatty and hydropic degeneration, inflammation, and eventually
      fibrosis, the condition is designated non-alcoholic steatohepatitis (NASH). The
      pathogenesis of these lesions is not clearly understood, but they are associated
      with insulin resistance in most cases. As a result, abdominal fat tissue
      lipolysis and excessive fatty acid uptake by the liver occur. This, together with
      a disturbance of triglyceride export as VLDL, results in fatty liver development.
      Both the inflammatory and hepatocellular degenerative components of NASH are
      attributed to oxidative stress. Mitochondrial respiratory chain loss of activity
      plays a critical role in the genesis of latter stress. This may be initiated by
      an increase in the hepatic TNFalpha, iNOS induction, peroxynitrite formation,
      tyrosine nitration and inactivation of enzymes making up this chain. Consequences
      of oxidative stress include: lipid peroxidation in cell membranes, stellate cell
      activation in the liver, liver fibrosis, chronic inflammation, and apoptosis.

PMID- 17198478
TI  - Inflammation and perforation of a solitary diverticulum of the cecum. A report of
      5 cases and literature review.
AB  - Solitary diverticulum of the cecum is a benign condition uncommon in the Western
      world, and with a higher incidence in Asian population. They are usually
      asymptomatic, and manifest clinically only with complications such as
      inflammation, perforation, or bleeding. They are a rare cause of acute abdominal
      pain, clinically similar to acute appendicitis, with tenderness in the right
      lower quadrant, fever, and leukocytosis. In spite of the information provided by
      ultrasonography or CT scans, a correct preoperative diagnosis is still difficult
      to reach, and is usually arrived at in the operating theater; differentiation
      from a neoplasm may be also sometimes complicated, and a wide surgical resection
      is usually required for such cases. We report on 5 cases of inflammation and
      perforation of a solitary cecal diverticulum, and perform a literature review.

PMID- 17198479
TI  - Gastrointestinal affectation with cytomegalovirus in an immunocompetent patient.

PMID- 17198480
TI  - Lipoma of the pancreas: diagnosis and management of these rare tumors.

PMID- 17198481
TI  - [Fistulizing gastroduodenal Crohn's disease histologically mimicking MALT
      lymphoma].

PMID- 17198482
TI  - [Controversy in the surgical treatment of the rectal carcinoid tumor].

PMID- 17198485
TI  - Clinical utility of office-based cognitive predictors of fitness to drive in
      persons with dementia: A systematic review.
AB  - OBJECTIVES: To perform a systematic review of evidence available regarding in
      office cognitive tests that differentiate safe from unsafe drivers with dementia.
      DESIGN: A comprehensive literature search of multiple databases including
      Medline, CINAHL, PsychInfo, AARP Ageline, and Sociofile from 1984 to 2005 was
      performed. This was supplemented by a search of Current Contents and a review of
      the bibliographies of all relevant articles. SETTING: English prospective cohort,
      retrospective cohort, and case-control studies that used accepted diagnostic
      criteria for dementia or Alzheimer's disease and that employed one of the primary
      outcomes of crash, simulator assessment, or on-road assessment were included.
      PARTICIPANTS: Two reviewers. MEASUREMENTS: The reviewers independently assessed
      study design, main outcome of interest, cognitive tests, and population details
      and assigned a Newcastle-Ottawa quality assessment rating. RESULTS: Sixteen
      articles met the inclusion criteria. Tests recommended by guidelines (e.g., the
      American Medical Association (AMA) and Canadian Medical Association guidelines)
      for the assessment of fitness to drive did not demonstrate robustly positive
      findings (e.g., Mini-Mental State Examination, Trails B) or were not evaluated in
      any of the included studies (e.g., Clock Drawing). Fifteen studies did not report
      any cutoff scores. CONCLUSION: Without validated cutoff scores, it is impossible
      to employ tests in a standardized fashion in front-line clinical settings. This
      study identified a research gap that will prevent the development of evidence
      based guidelines. Recommendations to address this gap are that driving
      researchers routinely perform cutoff score analyses and that stakeholder
      organizations (e.g., AMA, American Geriatrics Society) sponsor consensus fora to
      review driving research methodologies.

PMID- 17198486
TI  - Dynamic balance and stepping versus tai chi training to improve balance and
      stepping in at-risk older adults.
AB  - OBJECTIVES: To compare the effect of two 10-week balance training programs,
      Combined Balance and Step Training (CBST) versus tai chi (TC), on balance and
      stepping measures. DESIGN: Prospective intervention trial. SETTING: Local senior
      centers and congregate housing facilities. PARTICIPANTS: Aged 65 and older with
      at least mild impairment in the ability to perform unipedal stance and tandem
      walk. INTERVENTION: Participants were allocated to TC (n = 107, mean age 78) or
      CBST, an intervention focused on improving dynamic balance and stepping (n = 106,
      mean age 78). MEASUREMENTS: At baseline and 10 weeks, participants were tested in
      their static balance (Unipedal Stance and Tandem Stance (TS)), stepping (Maximum
      Step Length, Rapid Step Test), and Timed Up and Go (TUG). RESULTS: Performance
      improved more with CBST than TC, ranging from 5% to 10% for the stepping tests
      (Maximum Step Length and Rapid Step Test) and 9% for TUG. The improvement in TUG
      represented an improvement of more than 1 second. Greater improvements were also
      seen in static balance ability (in TS) with CBST than TC. CONCLUSION: Of the two
      training programs, in which variants of each program have been proven to reduce
      falls, CBST results in modest improvements in balance, stepping, and functional
      mobility versus TC over a 10-week period. Future research should include a
      prospective comparison of fall rates in response to these two balance training
      programs.

PMID- 17198487
TI  - Association between hormones and metabolic syndrome in older Italian men.
AB  - OBJECTIVES: To determine whether low levels of testosterone, sex hormone binding
      globulin (SHBG), insulin-like growth factor-1 (IGF-1), and dehydroepiandrosterone
      sulfate (DHEAS) and high levels of cortisol and leptin would be associated with
      metabolic syndrome (MS). DESIGN: Cross-sectional. SETTING: Population-based
      sample of older Italian men. PARTICIPANTS: Four hundred fifty-two men aged 65 and
      older enrolled in the Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS:
      Complete data on testosterone, cortisol, DHEAS, SHBG, fasting insulin, IGF-1 and
      leptin. MS was defined according to Adult Treatment Panel III criteria. RESULTS:
      MS was present in 73 men (15.8% of the sample). After adjusting for confounders,
      total testosterone (P < .05) and log (SHBG) (P < .001) were inversely associated,
      whereas log (leptin) was positively associated with MS (P < .001). Independent of
      age, log (SHBG) was positively associated with high-density lipoprotein
      cholesterol (P < .05) and negatively associated with abdominal obesity (P < .001)
      and triglycerides (P < .001). Log (leptin) was significantly associated with each
      component of MS. Cortisol, DHEAS, free and bioavailable testosterone, and IGF-1
      were not associated with MS. Having three or more hormones in the lower (for
      hormones lower in MS) or the upper (for hormones higher in MS) quartile was
      associated with three times the risk of being affected by MS (odds ratio = 2.8,
      95% confidence interval = 1.3-6.9) (P = .005), compared with not having this
      condition. CONCLUSION: Total testosterone and SHBG are negatively and leptin is
      positively associated with MS in older men. Whether specific patterns of hormonal
      dysregulation predict the development of MS should be tested in longitudinal
      studies.

PMID- 17198488
TI  - Evolution of prevalence of depressive symptoms and antidepressant use between
      1988 and 1999 in a large sample of older French people: Results from the
      personnes agees quid study.
AB  - OBJECTIVES: To describe the evolution of prevalence of depressive symptoms and
      antidepressant use between 1988 and 1999 in a large representative sample of
      older community-dwelling French people. DESIGN: Prospective cohort designed in
      1988/89 to study cerebral and functional aging. SETTING: Urban and rural
      communities in southwestern France. PARTICIPANTS: Three thousand six hundred
      thirty-seven adults aged 65 and older living in noninstitutional settings at
      baseline. MEASUREMENTS: Participants were interviewed 3, 5, 8, and 10 years after
      the initial data collection. Depressive symptomatology was evaluated using a
      French version of the Center for Epidemiological Studies Depression Scale.
      Longitudinal analysis of the prevalence of depressive symptomatology was
      performed using a logistic mixed model adjusted for antidepressant use, sex, age,
      education level, living conditions, psychiatric antecedents, drug consumption,
      and diagnosis of dementia. RESULTS: Over the 10 years of follow-up, the
      prevalence of depressive symptomatology decreased from 13.8% to 8.3%. This
      decrease was statistically significant even after adjustment (odds ratio = 0.88
      per increased year, 95% confidence interval = 0.85-0.90) and was more pronounced
      in subjects having reported previous depression at baseline. During the same
      period, antidepressant use rose from 5.2% to 11.9%, mainly due to increased use
      of selective serotonin reuptake inhibitors. Furthermore, the proportion of
      subjects who had depressive symptoms and did not use antidepressants decreased
      from 11.8% to 6.2%. CONCLUSION: This study suggests better management of late
      life depression in the last decade and illustrates the heterogeneity of
      depression disorder in late life.

PMID- 17198489
TI  - Longitudinal change in positive affect in community-dwelling older persons.
AB  - OBJECTIVES: To determine whether positive affect, defined as emotional
      contentment and happiness, remains stable in late life and to identify predictors
      of longitudinal change in positive affect. DESIGN: Longitudinal observational
      study. SETTING: Community. PARTICIPANTS: Six hundred sixty-three individuals aged
      70 and older without disability at baseline and free of chronically depressed
      mood. MEASUREMENTS: Positive affect, social network, social activity, chronic
      health conditions, activities of daily living, instrumental activities of daily
      living (IADLs), cognitive functioning, and negative affect measured over 54
      months, at 18-month intervals, up to four times. RESULTS: Positive affect
      remained relatively stable over 4.5 years of follow-up. Higher average levels of
      social activity and lower levels of negative affect were associated with higher
      positive affect. An increase of 1 point in negative affect (on a 7-point scale)
      was associated with a 0.23-point concurrent decrease in positive affect (on a 5
      point scale). Needing help in an additional IADL was associated with a decrease
      in positive affect of 0.04 points. A greater number of chronic conditions at
      enrollment was associated with lower positive affect. CONCLUSION: Positive affect
      is directly correlated with social involvement and inversely correlated with
      negative affect, IADL functioning, and comorbidity. Positive affect was mostly
      related to factors that do not change over time, although it showed some
      sensitivity to short- and long-term changes in physical health and functioning.

PMID- 17198490
TI  - Methicillin-resistant Staphylococcus aureus colonization is associated with
      higher mortality in nursing home residents with impaired cognitive status.
AB  - OBJECTIVES: To assess the effect of methicillin-resistant Staphylococcus aureus
      (MRSA) colonization on morbidity and mortality of nursing home residents. DESIGN:
      Three-year cohort study from 2000 to 2003. SETTING: Twenty-three nursing homes of
      all types and regions in the northern part of Belgium (Flanders). PARTICIPANTS:
      Two thousand eight hundred fourteen nursing home residents. MEASUREMENTS: The
      consequences of MRSA colonization on mortality and hospitalization were studied,
      adjusting for potential confounders. Dates and cause of death and hospitalization
      were collected every 6 months during 3 years of follow-up. RESULTS: After
      adjustment for age, sex, and Charlson comorbidity index, the risk for 36-month
      mortality remained significantly higher in MRSA carriers (hazard ratio (HR) =
      1.4, 95% confidence interval (CI) = 1.1-1.8) than in noncarriers. The effect of
      MRSA on mortality was dependent on the degree of cognitive impairment, with the
      highest effect in patients with severe cognitive impairment (adjusted HR = 1.8,
      95% CI = 1.1-2.8) and absence of effect in residents with good mental status
      (adjusted HR = 0.8, 95% CI = 0.43-1.62). Deaths were more frequently reported to
      be infection-related in MRSA carriers. No association was found between MRSA
      colonization and hospitalization for any reason, but during follow-up, MRSA
      carriers were twice as frequently hospitalized for respiratory tract infections.
      CONCLUSION: Colonization of MRSA in Belgian nursing home residents was associated
      with higher mortality. This excess mortality was restricted to residents with
      impaired cognitive function, probably reflecting differences in therapeutic
      approaches, in delay of diagnosis of pneumonia and other acute disorders in these
      patients, or in both.

PMID- 17198491
TI  - Nutritional formula improved immune profiles of seniors living in nursing homes.
AB  - OBJECTIVES: To assess whether an experimental nutritional formula (EXP) supports
      immune function in seniors living in long-term care facilities. DESIGN:
      Prospective, randomized, double-blind, controlled trial conducted September 2002
      through January 2003. SETTING: North central Florida nursing homes. PARTICIPANTS:
      Subjects aged 65 and older (n = 157). INTERVENTION: Subjects received 240 mL/d of
      EXP or standard liquid nutrition (CON) for 4 weeks before and 6 weeks after an
      influenza vaccination. MEASUREMENTS: Influenza vaccine antibody responses,
      immunophenotyping, lymphocyte activation, cytokines, and clinical measures
      (fever, number of prescribed antibiotics). RESULTS: Ninety-two subjects (n = 40,
      CON; n = 52, EXP) completed the study. Geometric mean antibody titers were
      similar between groups, yet the percentage of subjects with H1N1 antibody titers
      greater than 100 postvaccination was higher in the EXP group than in the CON
      group (43% vs 23%, P=.047). Similar trends were found for the percentage of
      subjects (intent to treat) with fourfold increases against the B/Hong Kong
      component (64% vs 46%, P = .09) or with H3N2 antibody titers of 40 or more (97%
      vs 89%, P=.06). EXP subjects had higher levels of influenza-activated lymphocytes
      (CD69+ and CD25+). Cytokine production after mitogen activation was lower in EXP
      than CON subjects (interleukin (IL)-6: 20+/-3 vs 29+/-3 ng/mL, P = .045; IL-10:
      310+/-60 vs 603+/-140 pg/mL, P = .06). Fewer EXP subjects were treated for fever
      (5% vs 16%, P = .02) or prescribed antibiotics (7 vs 11 new antibiotics/100 days
      of study, P = .06). CONCLUSION: Seniors consuming the EXP formula demonstrated
      enhanced immune function, indicated by increased influenza vaccine response and
      lymphocyte activation, less fever, and fewer newly prescribed antibiotics than
      those consuming a standard ready-to-drink nutritional supplement.

PMID- 17198492
TI  - Visual acuity, contrast sensitivity, and mortality in older women: Study of
      osteoporotic fractures.
AB  - OBJECTIVES: To determine whether poorer visual acuity and contrast sensitivity
      are independent risk factors for all-cause and traumatic mortality in older
      women. DESIGN: Twelve-year prospective cohort study (1986-2003). SETTING: Four
      U.S. clinical centers. PARTICIPANTS: Nine thousand seven hundred four
      postmenopausal white women aged 65 and older. MEASUREMENTS: Habitually corrected
      binocular visual acuity and low- and high-frequency contrast sensitivity were
      measured at baseline using a standard protocol. A study physician adjudicated the
      primary cause of death from death certificates and medical record review.
      RESULTS: During an average of 12.2 years of follow-up, 3,427 women died (35%), 72
      (0.7%) from traumatic events. In multivariate models adjusted for age, chronic
      medical problems, and smoking, all-cause mortality risk was 19% greater for
      persons in the worst quartile of visual acuity than for those in the best (hazard
      ratio (HR) = 1.19, P = .008) and 39% greater for persons with the worst contrast
      sensitivity (HR = 1.39, P < .001) than for those with the best. Traumatic
      mortality risk was 2.4 times greater for women with the worst contrast
      sensitivity than for those with the best (HR = 2.44, P = .03). CONCLUSION: Poorer
      visual acuity and contrast sensitivity are associated with greater risk of
      traumatic and all-cause mortality in older women, even after controlling for
      demographic and clinical characteristics. Although further research is necessary
      to determine how treating reversible causes of visual impairment or improving
      current refraction affects mortality in older women, clinical detection and
      follow-up of these visual impairments holds promise for identifying those who are
      at risk of mortality from other systemic conditions.

PMID- 17198493
TI  - Prognostic significance of micturition disturbances after acute stroke.
AB  - OBJECTIVES: To investigate the prevalence, incidence, clinical types, and
      prognostic effect of micturition disturbances in acute stroke. DESIGN:
      Prospective observational study. SETTING: Geriatric department (stroke and
      rehabilitation unit) in a community hospital (acute phase); outpatient clinic,
      patients' own homes, or nursing homes (3 months follow-up). PARTICIPANTS: Three
      hundred fifteen patients (mean age 77) with acute first-ever or recurrent stroke
      consecutively admitted to the hospital stroke unit. MEASUREMENTS: Premorbid basic
      and instrumental activities of daily living (ADLs) and mental functioning;
      comorbidity; previous and actual micturition symptoms; stroke syndromes;
      medication use; and poststroke mobility, ADLs, and cognition. RESULTS: One
      hundred forty-seven patients (46%) had preexisting micturition disturbances
      (urinary incontinence (UI), n = 98; urgency/frequency, n = 37; voiding
      difficulties, n = 12). Seventy-eight developed new symptoms (UI, n = 65;
      urgency/frequency, n = 4; sustained retention, n = 9). There were two UI types:
      urge UI (n = 27) and UI with impaired awareness of bladder needs (IA UI, n = 38).
      In regression analyses, IA UI was the only micturition disturbance predicting
      mortality and need for nursing home care at 3 months (odds ratio (OR) = 27.5, 95%
      confidence interval (CI) = 7.0-108.2), together with poor mobility (OR = 8.2, 95%
      CI = 2.6-26.2), and partial or total anterior circulation stroke type (OR = 3.6,
      95% CI = 1.4-9.0). CONCLUSION: New-onset poststroke UI with impaired awareness of
      bladder needs is a strong and independent risk factor for poor outcome at 3
      months. This probably reflects more serious brain damage, affecting sustained
      attention and information processing. Valid clinical tools to detect such
      dysfunction in stroke victims are needed. Clinical classification of poststroke
      UI is likely to improve management.

PMID- 17198494
TI  - Adjusted mortality after hip fracture: From the cardiovascular health study.
AB  - OBJECTIVES: To estimate the risk of death associated with hip fracture (HFx),
      stratifying by sex and time since fracture. DESIGN: Prospective cohort study
      compared participants with and without hip fracture, matched on sex, age, race,
      recruitment period, and time since enrollment. SETTING: The Cardiovascular Health
      Study, a more-than-15-year longitudinal study of 5,888 older individuals from
      four U.S. sites. PARTICIPANTS: Three hundred seventy-nine individuals with HFx
      were compared with 1,134 without HFx. MEASUREMENTS: Extended Cox models were used
      to estimate mortality hazard ratios (HRs) for different periods after fracture,
      adjusting for prefracture health. RESULTS: Age- and race-adjusted excess
      mortality was 9% in women and 24% in men 1 year after fracture, and 24% in women
      and 26% men 5 years postfracture. Multivariable-adjusted HRs of mortality
      associated with HFx in women were 7.1 (95% confidence interval (CI) = 2.3-21.5),
      2.1 (95% CI = 1.0-4.1), 1.4 (95% CI = 1.1-2.0), and 1.0 (95% CI = 0.6-1.5) for 0
      to 1 months, 2 to 6 months, 7 months to 4 years, and 5 to 8 years, respectively,
      after index date. In men, respective HRs for the same time periods were 39.9 (95%
      CI = 5.2-308.7), 3.8 (95% CI = 1.4-10.3), 1.1 (95% CI = 0.7-1.8), and 1.0 (95% CI
      = 0.3-2.7). HRs adjusted for age and race were 20% to 40% higher. CONCLUSION: The
      risk of mortality was highest in the first 6 months after HFx. In men, the risk
      of death approximated that of men without HFx after 6 months; in women, a
      moderately greater risk persisted through the fourth year. Although the mortality
      pattern was different in women and men, excess mortality 5 years postfracture was
      similar for both sexes.

PMID- 17198495
TI  - Management of noncancer pain in community-dwelling persons with dementia.
AB  - OBJECTIVES: To explore the pharmacological treatment of noncancer pain in persons
      with dementia and identify predictors associated with insufficient analgesia.
      DESIGN: Cross-sectional analysis of an observational cohort study. SETTING:
      Academic outpatient geriatric clinic in Chicago, Illinois. PARTICIPANTS: A total
      of 115 dyads, mostly African American, consisting of community-dwelling persons
      with dementia and their caregivers. MEASUREMENTS: Patient report of demographics,
      noncancer pain, function, cognition, and depression. Caregiver report of patient
      agitation and over-the-counter and prescription medications. RESULTS: Sixty-two
      of 115 (54%) patients reported pain "on an average day." The caregivers of more
      than half of persons with dementia who reported pain "on an average day" did not
      report analgesic use. The majority of caregivers who reported analgesic use
      reported that patients took a World Health Organization Class I medication. No
      patients had been prescribed a Class III (strong opioid) drug. Fifty-three of 115
      (46%) patients had potentially insufficient analgesia. In the logistic
      regression, insufficient analgesia was associated with greater age, Mini-Mental
      State Examination score of less than 10, and impairment in daily functioning.
      Insufficient analgesia was 1.07 times as likely (95% confidence interval (CI) =
      1.01-1.14) for each additional year of age, 3.0 times as likely (95% CI = 1.05
      9.10) if the subject had advanced dementia, and 2.5 times as likely (95% CI =
      1.01-6.25) if the patient had any impairment in activities of daily living.
      CONCLUSION: In this convenience sample from a geriatric clinic, many persons with
      dementia and noncancer pain were not receiving pharmacological treatment. Those
      at greatest risk for insufficient analgesia were older, had moderate to severe
      dementia, and experienced impairments in activities of daily living.

PMID- 17198496
TI  - Multimorbidity and survival in older persons with colorectal cancer.
AB  - OBJECTIVES: To ascertain the effect of common chronic conditions on mortality in
      older persons with colorectal cancer. DESIGN: Retrospective cohort study.
      SETTING: Population-based cancer registry. PARTICIPANTS: Patients in the
      Surveillance Epidemiology and End Results-Medicare linked database who were aged
      67 and older and had a primary diagnosis of Stage 1 to 3 colorectal cancer during
      1993 through 1999. MEASUREMENTS: Chronic conditions were identified using claims
      data, and vital status was determined from the Medicare enrollment files. After
      estimating the adjusted hazard ratios for mortality associated with each
      condition using a Cox model, the population attributable risk (PAR) was
      calculated for the full sample and by age subgroup. RESULTS: The study sample
      consisted of 29,733 patients, 88% of whom were white and 55% were female.
      Approximately 9% of deaths were attributable to congestive heart failure (CHF;
      PAR = 9.4%, 95% confidence interval (CI) = 8.4-10.5%), more than 5% were
      attributable to chronic obstructive pulmonary disease (COPD; PAR = 5.3%, 95% CI =
      4.7-6.6%), and nearly 4% were attributable to diabetes mellitus (PAR = 3.9%, 95%
      CI = 3.1-4.8%). The PAR associated with CHF increased with age, from 6.3% (95% CI
      = 4.4-8.8%) in patients aged 67 to 70 to 14.5% (95% CI = 12.0-17.5%) in patients
      aged 81 to 85. Multiple conditions were common. More than half of the patients
      who had CHF also had diabetes mellitus or COPD. The PAR associated with CHF alone
      (4.29%, 95% CI = 3.68-4.94%) was similar to the PAR for CHF in combination with
      diabetes mellitus (3.08, 95% CI = 2.60-3.61%) or COPD (3.93, 95% CI = 3.41
      4.54%). CONCLUSION: A substantial proportion of deaths in older persons with
      colorectal cancer can be attributed to CHF, diabetes mellitus, and COPD.
      Multimorbidity is common and exerts a substantial effect on colorectal cancer
      survival.

PMID- 17198497
TI  - Pathogenic colonization of the stomach in enterally fed elderly patients:
      Comparing percutaneous endoscopic gastrostomy with nasogastric tube.
AB  - OBJECTIVES: To compare the gastric juice microbiota of older people fed through a
      percutaneous endoscopic gastrostomy tube (PEG) with that of those fed through a
      nasogastric tube (NGT). DESIGN: Prospective comparative study. SETTING: Nursing
      and skilled nursing wards. PARTICIPANTS: Fifty-four elderly PEG-fed and 52 NGT
      fed patients. MEASUREMENTS: Cultures from the oropharynx and the gastric juice.
      RESULTS: Pathogenic bacteria were isolated from the oropharynxes of 44% of the
      PEG-fed patients and 54% of the NGT-fed patients. The most frequent gram-negative
      bacilli isolated from the oropharynx were Proteus spp. (13-21%) and Pseudomonas
      aeruginosa (13-18%), with no significant difference between the groups. Isolation
      rates from the gastric juice were significantly more frequent in the NGT-fed
      patients than in the PEG-fed patients for Proteus spp. (4% vs 23%), Escherichia
      coli (6% vs 21%), and mixed flora (11% vs 27%). Significant correlation was found
      between high gastric pH and the isolation of bacteria in both groups (correlation
      coefficient = 0.58, P < .001). CONCLUSION: Gastric juice of PEG-fed patients
      harbors pathogenic bacteria in significant numbers. No significant difference was
      noted with respect to the rate of isolation of pathogenic bacteria from the
      oropharynx between the groups. Major bacterial pathogens, such as P. aeruginosa
      and Proteus spp., were isolated significantly more from the gastric juice of NGT
      fed patients. These results support the view that a bidirectional spread pattern
      of pathogens may take place in NGT-fed patients.

PMID- 17198498
TI  - Modifiable lifestyle factors and the metabolic syndrome in older men: Effects of
      lifestyle changes.
AB  - OBJECTIVES: To examine the influence of lifestyle factors and changes in these
      factors on risk of the metabolic syndrome in elderly men. DESIGN: Cross-sectional
      and longitudinal analyses of cohort study. SETTING: General practices in 24
      British towns. PARTICIPANTS: Three thousand fifty-one men aged 60 to 79 with no
      diabetes mellitus or diagnosis of coronary heart disease. MEASUREMENTS: Lifestyle
      factors (smoking, physical activity, alcohol intake, body weight, dietary fat and
      carbohydrate intake) including recent changes in the previous 3 years (physical
      activity and body weight); metabolic syndrome. RESULTS: After adjustment for each
      of the other modifiable lifestyle factors, overweight/obesity and physical
      inactivity were associated with a significantly higher risk of the metabolic
      syndrome, as were cigarette smoking and a high-carbohydrate diet (>57% of
      energy). Alcohol intake and dietary fat intake were not related to the metabolic
      syndrome. Long-term ex-smokers showed similar risk to never smokers. Taking up
      physical activity and losing weight in the previous 3 years were associated with
      a reduction in risk of the metabolic syndrome. CONCLUSION: Overweight/obesity,
      physical inactivity, a high-carbohydrate diet, and cigarette smoking are
      associated with higher risk of the metabolic syndrome in elderly men.
      Modification of lifestyle factors, even later in life, has considerable potential
      for primary prevention of the metabolic syndrome.

PMID- 17198499
TI  - Isolated urinary, fecal, and double incontinence: Prevalence and degree of
      soiling in stroke survivors.
AB  - OBJECTIVES: To investigate the prevalence of isolated urinary and fecal
      incontinence and double incontinence in community-living stroke survivors and to
      assess the degree of soiling. DESIGN: Community-based postal survey. SETTING:
      Leicestershire, United Kingdom. PARTICIPANTS: Sixty-four thousand seven hundred
      forty-nine community-dwelling residents (aged > or = 40) were randomly selected
      from the Leicestershire Health Authority register. Residents living in
      institutional settings were excluded. MEASUREMENTS: Respondents were asked about
      previous stroke, urinary and bowel symptoms, and general health and demographic
      details including age, sex, and ethnicity. Urinary incontinence was defined as
      leakage several times a month or more often. Major fecal incontinence was defined
      as soiling of underwear, outer clothing, furnishings, or bedding several times a
      month or more often. RESULTS: A 65% response rate to the postal survey was
      obtained, with the return of 39,519 eligible questionnaires; 4% (n = 1,483)
      reported stroke. Five percent of stroke survivors reported major fecal
      incontinence, with 4.3% reporting fecal and urinary incontinence and 0.8%
      reporting isolated fecal incontinence. Major fecal incontinence was four and a
      half times as prevalent in stroke survivors as in the nonstroke population, and
      stroke survivors were also twice as likely to report soiling of furnishings or
      bedding. Functional limitations influence the presence of fecal incontinence in
      the stroke and nonstroke population. CONCLUSION: Fecal incontinence is common in
      stroke survivors, and the degree of soiling can be considerable. Future research
      needs to explore the effect fecal incontinence can have on the lives of stroke
      survivors and on how it can best be managed in those living in the community.

PMID- 17198500
TI  - Detrusor underactivity: Clinical features and pathogenesis of an underdiagnosed
      geriatric condition.
AB  - Urinary incontinence and other lower urinary tract symptoms exert a major
      influence on the health and independence of frail older people. Detrusor
      underactivity (DU) is defined as a contraction of reduced strength and/or
      duration, resulting in prolonged bladder emptying and/or a failure to achieve
      complete bladder emptying within a normal time span. DU may influence the
      clinical presentation and impede the therapy of disorders as common and as
      disparate as detrusor overactivity, urinary retention, and benign prostatic
      hyperplasia. Urodynamically, nearly two-thirds of incontinent nursing home
      residents exhibit DU. The clinical diagnosis of DU when present alone or in
      association with other bladder conditions such as detrusor overactivity (detrusor
      hyperactivity with impaired contractility (DHIC)) is challenging, because
      symptoms lack adequate precision. A catheterized and increasingly noninvasive
      ultrasound-based postvoid residual assessment allows a bedside diagnosis of
      retention and may suggest the presence of DU in individuals (mostly women) with a
      low likelihood of bladder outlet obstruction (BOO). Nevertheless, it cannot
      differentiate primary DU from retention secondary to BOO. The management of
      individuals with DHIC remains unsatisfactory, because antispasmodic
      anticholinergic medications may worsen retention, whereas bethanechol does not
      improve bladder emptying. Human detrusor biopsies reveal axonal degeneration,
      muscle loss, and fibrosis in DU. Animal studies suggest that multiple risk
      factors, including retention itself, lack of estrogen, infection, inflammation,
      and aging, may contribute to DU. Priority areas for future research include
      efforts to facilitate clinical nonurodynamic diagnosis of probable DU plus
      translational research designed to address the pathogenesis of this complex
      multifactorial geriatric syndrome.

PMID- 17198501
TI  - Caring for the new uninsured: Hospital charity care for older people without
      coverage.
AB  - Despite near-universal coverage through Medicare, a number of elderly residents
      in the United States do not have health insurance coverage. To the author's
      knowledge, this study is the first to document trends in the use of hospital
      charity care by uninsured older people. Data from the New Jersey Charity Care
      Program, which subsidizes hospitals for services provided to low-income uninsured
      people, were used to analyze trends in charity care utilization by older people
      from 1999 to 2004. Charity care charges are standardized to uniform Medicaid
      reimbursement rates and inflation adjusted using the Medical Care Consumer Price
      Index. From 1999 to 2004, use of charity care by older people grew much faster
      than it did for younger patients. As a result, older people now account for a
      greater share of hospital charity care in New Jersey than children. Elderly users
      of charity care generated higher costs per patient than their younger
      counterparts. Cost differences were especially salient at the upper end of the
      distribution, where high-cost elderly patients used significantly more resources
      than high-cost patients in other age groups. These results highlight an emerging
      source of strain on the healthcare safety net and point to a growing population
      of uninsured residents who have costly and complex medical needs. Similar
      experiences are likely to be found in other states, especially those that have
      growing populations of elderly immigrants who are likely to lack health
      insurance.

PMID- 17198502
TI  - Cooperative dementia care clinics: A new model for managing cognitively impaired
      patients.
AB  - Cooperative health care clinics (CHCCs), or shared medical appointments, are a
      healthcare innovation that can improve access and expand physicians' capacity to
      manage common geriatric conditions. This report describes a pilot program and
      working model for extending CHCCs to patients with dementia. Three cooperative
      dementia care clinics (CDCCs) met monthly for up to 1 year, drawing participants
      from a dementia clinic roster of patients and caregivers who had required
      continued specialty care for at least 3 months. Twenty-six of 33 eligible patient
      caregiver dyads expressed interest, and 21 enrolled; five whose clinical status
      changed during the year withdrew and were replaced with new members. Brief
      introductory socialization, individualized clinical management, and an
      educational focus selected from problems of patients and caregivers were common
      to all sessions. Most participants required several types of clinical
      intervention and educational support. One group ended after reaching a natural
      termination point, and two others are ongoing at the request of participants.
      CDCCs can be a viable approach to increasing dementia care capacity in health
      systems. Formal service intervention trials to evaluate the generalizability and
      comparative effectiveness and economic viability of this model versus usual care
      are an appropriate next step.

PMID- 17198503
TI  - Office-based evaluation of the older driver.

PMID- 17198504
TI  - Self-neglect as a geriatric syndrome.

PMID- 17198506
TI  - Could self-neglect in older adults be a geriatric syndrome?

PMID- 17198507
TI  - Regarding "alcohol use, comorbidity, and mortality".

PMID- 17198509
TI  - The value of gait velocity test for high-function populations.

PMID- 17198510
TI  - Young, small, but not forgotten!

PMID- 17198512
TI  - End-of-life decisions and old-age mortality: A cross-country analysis.

PMID- 17198513
TI  - Agitated behavior as a prodromal symptom of physical illness: A case of
      influenza.

PMID- 17198514
TI  - Purple diaper syndrome in geriatrics.

PMID- 17198515
TI  - Over-the-counter medication labels: Problems and needs of the elderly population.

PMID- 17198516
TI  - Mandibular osteoporotic fracture: A case report.

PMID- 17198517
TI  - Dry cough as first manifestation of giant-cell arteritis.

PMID- 17198518
TI  - Temporal arteritis: The importance of recognizing senescent changes versus
      quiescent disease in a temporal artery biopsy.

PMID- 17198519
TI  - Is the current anti-osteoporotic therapy paradigm good enough?

PMID- 17198523
TI  - Diet, cholesterol metabolism, and Alzheimer's disease: Apolipoprotein E as a
      possible link?

PMID- 17198524
TI  - Apolipoprotein E genotypes in mild cognitive impairment subtypes.

PMID- 17198525
TI  - Mild cognitive impairment subtypes and vascular dementia.

PMID- 17198527
TI  - Short-term effect of dementia disclosure: how patients and families describe the
      diagnosis.

PMID- 17198528
TI  - An exceptional case of severe hypocalcemia.

PMID- 17198530
TI  - Keratoacanthoma arising after an arthropod sting.

PMID- 17198529
TI  - Loss of autonomy related to valproic acid intake.

PMID- 17198531
TI  - Treating hypertension in older people: Practical implications of achieving
      targets.

PMID- 17198532
TI  - Association between psychotropic drug use and heart failure therapy in elderly
      long-term care residents.

PMID- 17198533
TI  - The potential of melatonin in reducing morbidity-mortality after craniocerebral
      trauma.
AB  - Craniocerebral trauma (CCT) is the most frequent cause of morbidity-mortality as
      a result of an accident. The probable origins and etiologies are multifactorial
      and include free radical formation and oxidative stress, the suppression of
      nonspecific resistance, lymphocytopenia (disorder in the adhesion and activation
      of cells), opportunistic infections, regional macro and microcirculatory
      alterations, disruptive sleep-wake cycles and toxicity caused by therapeutic
      agents. These pathogenic factors contribute to the unfavorable development of
      clinical symptoms as the disease progresses. Melatonin (N-acetyl-5
      methoxytryptamine) is an indoleamine endogenously produced in the pineal gland
      and in other organs and it is protective agent against damage following CCT. Some
      of the actions of melatonin that support its pharmacological use after CCT
      include its role as a scavenger of both oxygen and nitrogen-based reactants,
      stimulation of the activities of a variety of antioxidative enzymes (e.g.
      superoxide dismutase, glutathione peroxidase, glutathione reductase and
      catalase), inhibition of pro-inflammatory cytokines and activation-adhesion
      molecules which consequently reduces lymphocytopenia and infections by
      opportunistic organisms. The chronobiotic capacity of melatonin may also reset
      the natural circadian rhythm of sleep and wakefulness. Melatonin reduces the
      toxicity of the drugs used in the treatment of CCT and increases their efficacy.
      Finally, melatonin crosses the blood-brain barrier and reduces contusion volume
      and stabilizes cellular membranes preventing vasospasm and apoptosis of
      endothelial cells that occurs as a result of CCT.

PMID- 17198534
TI  - Melatonin and anesthesia: a clinical perspective.
AB  - The hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow
      this neurohormone with the profile of a novel hypnotic-anesthetic agent.
      Sublingually or orally administered melatonin is an effective premedicant in
      adults and children. Melatonin premedication like midazolam is associated with
      sedation and preoperative anxiolysis, however, unlike midazolam these effects are
      not associated with impaired psychomotor skills or the quality of recovery.
      Melatonin administration also is associated with a tendency toward faster
      recovery and a lower incidence of postoperative excitement than midazolam. Oral
      premedication with 0.2 mg/kg melatonin significantly reduces the propofol and
      thiopental doses required for loss of responses to verbal commands and eyelash
      stimulation. In rats, melatonin and the more potent melatonin analogs 2
      bromomelatonin and phenylmelatonin have been found to have anesthetic properties
      similar to those of thiopental and propofol, with the added advantage of
      providing potent antinociceptive effects. The exact mechanism(s) by which
      structurally diverse intravenous and volatile anesthetics produce general
      anesthesia is still largely unknown, but positive modulation of gamma
      aminobutyric acid type A (GABAA) receptor function has been recognized as an
      important and common pathway underlying the depressant effects of many of these
      agents. Accumulating evidence indicates that there is interplay between the
      melatonergic and GABAergic systems, and it has been demonstrated that melatonin
      administration produces significant, dose-dependent increases in GABA
      concentrations in the central nervous system. Additional in vitro data suggest
      that melatonin alters GABAergic transmission by modulating GABAA receptor
      function. Of greater importance, data from in vivo studies suggest that the
      central anesthetic effects of melatonin are mediated, at least in part, via
      GABAergic system activation, as they can be blocked or reversed by GABAA receptor
      antagonists. Further work is needed to better understand the general anesthetic
      properties of melatonin at the molecular, cellular, and systems levels.

PMID- 17198535
TI  - Evidence supporting the use of melatonin in short gestation infants.
AB  - Pineal melatonin regulates circadian rhythms and influences sleep. Melatonin also
      has protective actions against tissue damage from free-radicals and other toxins.
      Evidence is presented that this indoleamine is involved in pre- and postnatal
      brain (and ocular) development and intrauterine growth. In the absence of
      maternal melatonin, short gestation infants have a prolonged period of melatonin
      deficiency. Melatonin supplementation, which has a benign safety profile, may
      help reduce complications in the neonatal period that are associated with short
      gestation. We believe that this treatment might result in a wide range of health
      benefits, improved quality of life and reduced healthcare costs.

PMID- 17198536
TI  - One molecule, many derivatives: a never-ending interaction of melatonin with
      reactive oxygen and nitrogen species?
AB  - Melatonin is a highly conserved molecule. Its presence can be traced back to
      ancient photosynthetic prokaryotes. A primitive and primary function of melatonin
      is that it acts as a receptor-independent free radical scavenger and a broad
      spectrum antioxidant. The receptor-dependent functions of melatonin were
      subsequently acquired during evolution. In the current review, we focus on
      melatonin metabolism which includes the synthetic rate-limiting enzymes,
      synthetic sites, potential regulatory mechanisms, bioavailability in humans,
      mechanisms of breakdown and functions of its metabolites. Recent evidence
      indicates that the original melatonin metabolite may be N1-acetyl-N2-formyl-5
      methoxykynuramine (AFMK) rather than its commonly measured urinary excretory
      product 6-hydroxymelatonin sulfate. Numerous pathways for AFMK formation have
      been identified both in vitro and in vivo. These include enzymatic and pseudo
      enzymatic pathways, interactions with reactive oxygen species (ROS)/reactive
      nitrogen species (RNS) and with ultraviolet irradiation. AFMK is present in
      mammals including humans, and is the only detectable melatonin metabolite in
      unicellular organisms and metazoans. 6-hydroxymelatonin sulfate has not been
      observed in these low evolutionary-ranked organisms. This implies that AFMK
      evolved earlier in evolution than 6-hydroxymelatonin sulfate as a melatonin
      metabolite. Via the AFMK pathway, a single melatonin molecule is reported to
      scavenge up to 10 ROS/RNS. That the free radical scavenging capacity of melatonin
      extends to its secondary, tertiary and quaternary metabolites is now documented.
      It appears that melatonin's interaction with ROS/RNS is a prolonged process that
      involves many of its derivatives. The process by which melatonin and its
      metabolites successively scavenge ROS/RNS is referred as the free radical
      scavenging cascade. This cascade reaction is a novel property of melatonin and
      explains how it differs from other conventional antioxidants. This cascade
      reaction makes melatonin highly effective, even at low concentrations, in
      protecting organisms from oxidative stress. In accordance with its protective
      function, substantial amounts of melatonin are found in tissues and organs which
      are frequently exposed to the hostile environmental insults such as the gut and
      skin or organs which have high oxygen consumption such as the brain. In addition,
      melatonin production may be upregulated by low intensity stressors such as
      dietary restriction in rats and exercise in humans. Intensive oxidative stress
      results in a rapid drop of circulating melatonin levels. This melatonin decline
      is not related to its reduced synthesis but to its rapid consumption, i.e.
      circulating melatonin is rapidly metabolized by interaction with ROS/RNS induced
      by stress. Rapid melatonin consumption during elevated stress may serve as a
      protective mechanism of organisms in which melatonin is used as a first-line
      defensive molecule against oxidative damage. The oxidative status of organisms
      modifies melatonin metabolism. It has been reported that the higher the oxidative
      state, the more AFMK is produced. The ratio of AFMK and another melatonin
      metabolite, cyclic 3-hydroxymelatonin, may serve as an indicator of the level of
      oxidative stress in organisms.

PMID- 17198537
TI  - Melatonin-induced gene expression changes and its preventive effects on
      adriamycin-induced lipid peroxidation in rat liver.
AB  - Adriamycin (ADR) provokes lipid peroxidation process, while melatonin (MEL) is a
      free radical scavenger that has been found to protect against lipid peroxidation
      in vitro and in many experimental models. In the present study, the effects of
      ADR and the combination of ADR and MEL were analyzed on the modulation of fatty
      acid composition, lipid peroxidation and gene expression in rat liver. Sixty
      genes were selected for the study of relative gene expression changes in the
      liver. ADR treatment decreased the polyunsaturated fatty acids C22:6 n-3 and
      C20:4 n-6 in rat liver mitochondria. When the treatment of ADR was followed by
      MEL, decrease in these fatty acids could not be detected. A significant increase
      in lipid peroxidation was observed after administration of ADR, which was
      restored to control values by post-treatment with MEL. Gene expression profiles
      of ADR- versus ADR+MEL-treated rat livers indicated that both treatments induced
      significant changes. Quantitative real-time polymerase chain reaction analysis of
      60 genes involved in oxidative stress revealed that cyp1b1, which is involved in
      electron transport, cyclin-dependent kinase inhibitor 1a that possesses cyclin
      dependent protein kinase inhibitor activity, was induced at a more pronounced
      level in the ADR+MEL-treated samples than in the ADR-treated ones. Several genes
      having roles in heat-shock response were downregulated in MEL-treated animals,
      such as hsp40, hsp70 and hsp90 proteins reflecting the reduced oxidative stress
      in these animals. Global gene expression analysis will highlight the gene
      expression changes accompanying oxidative damage and its prevention in more
      details.

PMID- 17198538
TI  - Antioxidant effects of melatonin in rats during chronic exposure to hyperbaric
      oxygen.
AB  - In addition to its beneficial effects, hyperbaric oxygen (HBO) exposure causes
      some detrimental effects via oxidative stress. Previous experimental studies
      showed that melatonin is a useful agent to block single session HBO-induced
      oxidative stress. In the present study, we investigated the antioxidant effect of
      exogenously administered as well as endogenously produced melatonin in lung and
      brain tissues of rats exposed to long term HBO. The HBO procedure was set as
      daily exposures to 2.5 ATA of oxygen for 1 hr and a total of 10 sessions. Twenty
      eight male Sprague-Dawley rats were divided into four groups as follows: control,
      daytime HBO, daytime HBO plus melatonin (5 mg/kg), nighttime HBO. Tissue
      oxidative/antioxidant status was examined by determining the protein carbonyl
      content as a criteria for oxidative stress and the activities of the antioxidant
      enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). HBO
      exposure for 10 days caused significant increases in protein carbonyl content and
      SOD levels of lung and brain, but GSH-Px activities remained unaffected. The
      increases in protein carbonyls were blocked by exogenously administered melatonin
      and in part by nighttime exposure to darkness whereas the increase of SOD
      activity was only impeded by endogenously produced melatonin in brain tissue.
      Lung SOD activity was augmented by endogenous melatonin. In conclusion, melatonin
      blocks long-term HBO-induced cumulative oxidative stress as indicated changes in
      protein carbonyls. Both exogenously injected and physiologically secreted
      melatonin has this potential. The effects of HBO-exposure and melatonin on the
      activities of the antioxidative enzymes are less clear.

PMID- 17198539
TI  - Melatonin reduces ventricular arrhythmias and preserves capillary perfusion
      during ischemia-reperfusion events in cardiomyopathic hamsters.
AB  - Earlier studies showed that melatonin has powerful antioxidative effects on
      ischemia-reperfusion (I/R) injury in healthy hamsters. In the present study, the
      possible protective effects of melatonin in 10-month-old cardiomyopathic (CM)
      hamsters were evaluated in a model of I/R in the cheek pouches observed by
      intravital microscopy. In CM (BIO 14.6) hamsters diameter, red blood cell (RBC)
      velocity and flow in arterioles as well as lipid peroxide and nitrite/nitrate
      concentrations in the systemic blood, perfused capillary length, vascular
      permeability, and leukocyte adhesion were measured after melatonin injection (6
      mg/kg intraperitoneally daily for 3 weeks), and after I/R. The influence of
      melatonin on the incidence of postischemic-reperfusion-induced ventricular
      tachycardia (VT) and ventricular fibrillation (VF) were also measured. Changes in
      the arteriolar response to NG-monomethyl-L-arginine (L-NMMA), a nitric oxide
      inhibitor, norepinephrine (NE), and angiotensin II (ANG II) were studied before
      and after melatonin injection (10 mg/kg intravenously). In CM hamsters, melatonin
      restored normal arteriolar responses to L-NMMA, NE, and ANG II. I/R elevated
      lipid peroxide and nitrate/nitrite levels, and vascular permeability while
      arteriolar diameter, RBC velocity, flow and capillary perfusion were reduced.
      These effects were more marked in CM versus healthy hamsters. During I/R
      melatonin reduced oxidative and nitrosative stress, vasoconstriction, leukocyte
      adhesion, and vascular permeability and increased capillary perfusion. Melatonin
      reduced the incidence of VT while VF during reperfusion disappeared totally. In
      conclusion, melatonin prevents both microvascular injury and ventricular
      arrhythmias during postischemic reperfusion by modulating the lipid peroxide
      overproduction and nitrative stress which are involved in the development of
      cardiomyopathy.

PMID- 17198540
TI  - Effect of exogenous administration of melatonin and growth hormone on pro
      antioxidant functions of the liver in aging male rats.
AB  - Aging is accompanied by changes in the morphology and physiology of organs and
      tissues, such as the liver. This process might be due to the accumulation of
      oxidative damage induced by reactive oxygen (ROS) and reactive nitrogen species
      (RNS). Hepatocytes are very rich in mitochondria and have a high respiratory
      rate, so they are exposed to large amounts of ROS and permanent oxidative stress.
      Twenty-four male Wistar rats of 22 months of age were divided into three groups.
      One group remained untreated and acted as the control group. The second was
      treated with growth hormone (GH) (2 mg/kg/d sc) and the third was submitted to
      treatment wit 1 mg/kg/d of melatonin in the drinking water. A group of 2-months
      old male rats was used as young controls. After 10 wk of treatment the rats were
      killed by decapitation, and the liver was dissected and homogenized.
      Mitochondrial, cytosolic and microsomal fractions were obtained and cytochrome C,
      glutathione peroxidase, s-transferase and nitric oxide (NO) were measured. Aging
      induced a significant increase in mitochondrial nitric oxide. An increase in
      cytochrome C in the cytosolic fraction and a reduction in the mitochondrial
      fraction with age was also observed. Both GH and melatonin treatments
      significantly reduced the enhanced measures and increased the reduced values. A
      reduction in glutathione peroxidase and glutathione S-transferase was found in
      old control rats when compared with the group of young animals. Treatment for 2.5
      months of old rats with GH and melatonin were able to increase the enzymes
      reaching values similar to those found in young animals. In conclusion, GH and
      melatonin treatment seems to have beneficial effects against age-induced damage
      in the liver.

PMID- 17198541
TI  - Melatonin protects against oxidative damage and restores expression of GLUT4 gene
      in the hyperthyroid rat heart.
AB  - To understand the mechanism of cardiovascular dysfunction in the hyperthyroid
      condition, the role of oxidative stress was examined in rats treated with 3,5,3'
      triiodo-l-thyronine (T3). Treatment of rats daily with T3 (8 microg/100 g BW) for
      15 days resulted in an increase in heart weight to body weight ratio, which was
      ameliorated by antioxidants, melatonin (2 mg/100 g BW) or vitamin E (4 mg/100 g
      BW). Both melatonin and vitamin E also inhibited rises of lipid peroxidation and
      hydroxyl radical generation and prevented the inhibition of Cu,Zn-superoxide
      dismutase in the hypertrophic heart. The expression of the glucose transporter,
      GLUT4, was reduced in response to T3, which was completely restored by melatonin
      and partially by vitamin E. However, neither antioxidant prevented down
      regulation of peroxisome proliferator-activated receptor-alpha in the
      hyperthyroid heart. Furthermore, the reduced level of myocyte enhancer factor-2,
      a regulator of GLUT4 transcription was restored completely by melatonin and
      partially by vitamin E treatment. Glucose uptake in hypertrophic left ventricular
      cells was also restored by these antioxidants. The expression of B-type
      natriuretic peptide, a marker of heart failure, was significantly increased by T3
      and ameliorated by melatonin or vitamin E treatments. In general, the beneficial
      effects of melatonin given as a co-treatment with T3 were better than those
      induced by vitamin E. These data show that melatonin ameliorates hypertrophic
      growth of the myocardium induced by hyperthyroidism and provide an insight into
      the mechanism of reactive oxygen species-mediated down regulation of
      metabolically important genes such as GLUT4 in the heart.

PMID- 17198542
TI  - Clock gene expression in the retina of melatonin-proficient (C3H) and melatonin
      deficient (C57BL) mice.
AB  - In several mammalian species, the retina contains an autonomous circadian clock
      and is capable of synthesizing melatonin. The function of circadian clocks
      depends on interlocking transcriptional/translational feedback loops involving
      several clock genes. Here we investigated the expression of two clock genes
      (Per1, Cry2) and the level of phosphorylated (p) cyclic AMP response element
      binding protein (CREB) in retinae of melatonin-deficient (C57BL) with an intact
      retina and melatonin-proficient (C3H) mice with degenerated outer nuclear layer.
      RNase protection assay and in situ hybridization revealed in both strains a
      rhythm in transcript levels for Per1 with a peak at zeitgeber time (ZT) 08, but
      not for Cry2. Immunoreactions for PER1, CRY2 and pCREB were localized to the
      nuclei of cells in the inner nuclear layer (INL) and ganglion cell layer (GC) of
      both strains and to the outer nuclear layer of C57BL. In C3H, protein levels of
      PER1 and CRY2 followed a clear day/night rhythm in the INL and the GC with a peak
      at the end of the day (ZT14). pCREB levels peaked at the beginning of the day.
      Noteably, in melatonin-deficient C57BL mice, protein levels of PER1, CRY2 and
      pCREB did not show significant changes over a 16L/8D cycle. These data suggest
      that melatonin influences PER1 and CRY2 protein levels via post-transcriptional
      mechanisms and also plays a role in rhythmic regulation of pCREB levels in the
      mammalian retina.

PMID- 17198543
TI  - Expression and cellular localization of melatonin-synthesizing enzymes in the rat
      lens.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) prevents oxidative stress-induced
      cataract development, and previous studies have suggested that the ocular lens
      synthesizes melatonin. In the present study, we examined whether two key enzymes
      in melatonin biosynthesis, arylalkylamine N-acetyltransferase (AANAT) and
      hydroxyindole-O-methyltransferase (HIOMT), are expressed in the lens of adult
      male rats. Reverse transcriptase-polymerase chain reaction analyses demonstrated
      that both AANAT and HIOMT mRNAs are expressed in the lens. Western blotting for
      AANAT protein showed that the lens, like the pineal gland, contains this enzyme
      protein with a molecular mass of 24 kDa. Immunohistochemistry revealed that AANAT
      protein is localized to the lens cortical fiber cells. Serotonin, which is a
      substrate for AANAT and a melatonin precursor, was also found in this region.
      These findings demonstrate that the lens expresses AANAT and HIOMT, and suggest
      that the cortical fiber cells are the main melatonin-synthesizing sites in the
      lens. Locally synthesized melatonin in the lens cortical fiber cells may protect
      the lens itself from cataract development.

PMID- 17198544
TI  - Analysis of polymorphism, structure and function of exon 2 of ovine melatonin
      receptor 1b gene: a clue as to why it lacks expression in sheep.
AB  - To analyze the structure and function of the melatonin 1b receptor (MT2) in
      sheep, single nucleotide polymorphisms were detected in exon 2 of sheep MT2 gene
      using genomic DNA from five sheep breeds by five primers. Polymorphisms were
      found, and 33 nucleotide mutations were revealed by comparing the mutant types
      with the wild types. Among them, 14 give rise to deduced amino acid changes.
      However, none is likely to be associated with nonseasonal or seasonal estrus in
      sheep breeds tested. Sequence of exon 2 of MT2 of Small Tail Han sheep shows much
      closer phylogenetic relationship with predicted bovine and porcine MT2 than with
      human and mouse. The deduced amino acid sequence shows higher identity with the
      MT2 of cattle (95%) and pig (79%) than with human (76%) and mouse (71%). A rather
      high identity (61-63%) with the MT1 of sheep, human and mouse was also found.
      Compared with the other known MT2, 35 unique altered amino acids were revealed.
      Albeit it also contains a NAXXY motif in transmembrane 7, both a DRY motif and a
      CYVCR motif were detected just downstream from its third transmembrane domain
      rather than NRY and CYICH found in other melatonin receptor groups. We presumed
      that it is possible that the structural changes make its binding function to the
      ligands attenuated or disrupted, and other genes (most probably MT1) were
      substituted in the progress of evolution, which ultimately resulted in no
      detectable expression in current breeds of sheep.

PMID- 17198545
TI  - Evidence for the expression of both the MT1- and in addition, the MT2-melatonin
      receptor, in the rat pancreas, islet and beta-cell.

PMID- 17198547
TI  - [Oncological surgery of the pancreas and bile ducts: current therapeutic
      prospects].

PMID- 17198546
TI  - Risk factors and myocardial infarction in patients with obstructive sleep apnea:
      impact of beta2-adrenergic receptor polymorphisms.
AB  - BACKGROUND: The increased sympathetic nervous activity in patients with
      obstructive sleep apnea (OSA) is largely responsible for the high prevalence of
      arterial hypertension, and it is suggested to adversely affect triglyceride and
      high-density lipoprotein (HDL) cholesterol levels in these patients. The
      functionally relevant polymorphisms of the beta2-adrenergic receptor (Arg
      47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these
      risk factors in previous studies, but results are inconsistent. METHODS: We
      investigated a group of 429 patients (55 +/- 10.7 years; 361 men, 68 women) with
      moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 +/-
      23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1
      +/- 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2%
      of patients). We typed the beta2-adrenergic receptor polymorphisms and
      investigated the five most frequent haplotypes for their modifying effects on OSA
      induced changes in blood pressure, heart rate, and lipid levels. The prevalence
      of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and
      survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes
      and haplotypes. RESULTS: Multivariate linear/logistic regressions revealed a
      significant and independent (from BMI, age, sex, presence of diabetes, use of
      antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI
      on daytime systolic and diastolic blood pressure, heart rate, prevalence of
      hypertension, and triglyceride and HDL levels. The beta2-adrenergic receptor
      genotypes and haplotypes showed no modifying effects on these relationships or on
      the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for
      all three polymorphisms, heterozygous carriers had a significantly lower relative
      risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P =
      0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023).
      Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for
      all three polymorphisms) showed a five-fold lower prevalence of survived
      myocardial infarction (OR = 0.21, P = 0.023). CONCLUSION: Our study showed no
      significant modifying effect of the functionally relevant beta2-adrenergic
      receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid
      changes. Nevertheless, heterozygosity of these polymorphisms is associated with a
      lower prevalence of survived myocardial infarction in this group with, on
      average, a high cardiovascular risk profile.

PMID- 17198548
TI  - [Gastrointestinal stromal tumors: five case reports and review of the
      literature].
AB  - Being a rare entity, GISTs represents the most common subset of mesenchymal
      tumours that arise from the digestive tract. Their immunohistochemical and
      histopathologic features distinguish them from other gastrointestinal mesenchymal
      neoplasms. These tumours have been the matter of considerable debate in the
      literature regarding their histogenesis, criteria for diagnosis, prognostic
      features and treatment. GISTs express Kit protein that not only is a marker for
      diagnosis but has also permitted to identify a specific medical treatment. The
      exceptional interest aroused in the literature leads us to make a review about
      this subject reporting five cases treated in the last 2 years.

PMID- 17198549
TI  - Pathological evaluation in colorectal polyps endoscopic treatment.
AB  - This retrospective study shows that endoscopic polypectomy is the technique of
      choice to remove the majority of polyps; follow-up and pathologic examinations
      shed light on the carcinogenesis of colorectal lesions. From January 1990 to
      December 2001, 1302 adenomatous polyps were removed, 1175 endoscopically, 127
      with surgical procedures. The anatomical and morphologic conditions of the colon
      and some characteristics of the polyps represent limits to the feasibility and to
      the efficacy of polypectomy, and the most important variables for the correct
      management of the patients affected by colorectal adenomatous polyps.

PMID- 17198550
TI  - [Chilaiditi's syndrome: a rare cause of abdominal pain in the differential
      diagnosis of the abdominal perforation. Case report].
AB  - A case of a 92-years-old patient with abdominal pain and constipation is
      presented. He reported a recent traumatic fracture of the upper limb. Traditional
      diagnostic work-up for patient with abdominal pain was started up. He was
      submitted to abdominal film that demonstrated air underneath the diaphragm
      suggestive for perforation. This hallmark is opposed to clinical condition of
      patient, so differential diagnosis for rare Chilaiditi's syndrome was considered,
      because this syndrome is frequent in old patient. Diagnostic work-up was
      completed with upper abdominal CT that excluded intestinal perforation and
      confirmed the diagnosis of Chilaiditi's syndrome showing hepatodiaphragmatic
      interposition of the dilated colon. Therefore it was decided in favour of medical
      therapy. In the our case, in spite of negative clinical examination, the
      uncertain radiological hallmark obliged us to exclude diagnosis of abdominal
      perforative syndrome that needs emergency operation. Although the Chilaiditi's
      syndrome is rare, it must be considerated in differential diagnosis of
      perforative abdominal syndrome, when there are doubts about the subdiaphragmatic
      air in abdominal film.

PMID- 17198551
TI  - [Granulomatous mastitis: diagnostic and therapeutic problems. Case report and
      review of the literature].
AB  - The granulomatous mastitis is uncommon inflammatory disease of the breast of
      unknown etiology. The diagnosis is obtained only through hystopathology. We
      report a case of woman, 41 years old, showing lesions of the breast, that caused
      strong pain with ulcerations sero-haematic secretion and axillary omolateral
      lymphadenopathy. The diagnostic workup (sonography, mammography, multiples FNAB
      of single lesions, the culture of cells and hormonal profile) showed an
      inflammatory aspecific lesions with presence of atipic cells in nipple's
      secretion and in FNAB of periareola lesion. We performed an excisional biopsy.
      The hystopathologic diagnosis showed a granulomatous mastitis, confirming the
      validity of our diagnostic and therapeutic choices. The excisional biopsy has
      allowed to avoid an overtreatment and obtain a good aesthetic result.

PMID- 17198552
TI  - [Excision of a schwannoma of the neck: surgical technique].
AB  - We present a case of schwannoma of the neck in 49 year old man, symptomatic
      (paresthesia, cervical mass and dysphagia). After ultrasonography and magnetic
      resonance of the neck, the patient was operated and excision of the lesion was
      completely performed. The operation was performed through a cervical approach:
      the nerves and the vascular and muscular structures were carefully isolated and
      preserved. The tumour arised from the cervical sympathetic chain. The diagnosis
      of schwannoma was possible only by histopathologic examen. After 48 months no
      local recurrence or postoperative complication related to intervention were
      found. These lesions are uncommon. The identification of the nerve is often
      difficult until the operation, which is the treatment of choice for the
      schwannoma.

PMID- 17198553
TI  - Spigelian hernia: a case report and review of the literature.
AB  - Spigelian hernia is a rare abdominal hernia that occurs through Spigelian
      aponeurosis. The Authors present a case of Spigelian hernia associated with
      narrowing of sigmoid colon and diverticular pathology. They also described
      historical background, surgical anatomy and etiopathogenesis of this hernia. By a
      remarkable revision of literature, they sum up epidemiology and clinical features
      of Spigelian hernia. Furthermore, they discuss diagnostic and therapeutic
      principles.

PMID- 17198554
TI  - [Subareolar injection for sentinel lymph node biopsy in multiple breast cancer].
AB  - In this study we performed subdermal injection of 99mTc-labeled albumin combined
      with subareolar (SA) injection of blue dye to axillary lymphatic mapping and
      sentinel lymph node biopsy (SNLB) in patients with multifocal and multicentric
      breast cancer (MC) to evaluate the feasibility and accuracy of this technique. We
      compared the results with a group of patients with unifocal breast cancer. From
      January 1999 to March 2006 axillary lymph node mapping and SLNB was performed on
      250 patients followed by a complete axillary lymph node dissection. Retrospective
      analysis showed that 32 (12.8%) of these patients have MC on final
      histopathologic examination and 218 (87.2%) have unifocal cancer. In statistical
      analysis tumor size shows a significant difference (p=.01) with largest lesions
      in MC. In MC often histological type is invasive lobular with or without in situ
      cancer (p= .001). Metastatic lymph node involvement was significantly higher in
      the MC group compared to unifocal cancer group (p=.001). False negative (FN) rate
      was 5.8% in MC and 9.6% in unifocal cancers. The overall accuracy of lymphatic
      mapping was 96.8% in MC and 97.6% in unifocal cancers. Sensitivity was 94.4% in
      MC and 91.2% in unifocal cancers. In this study we provide further evidence that
      lymphatic mapping may be reliable even in patients with MC. SA injection
      technique demonstrates a high sentinel lymph node identification rate and low FN
      rate; therefore this technique should been recommended to SLNB in patients with
      MC of the breast.

PMID- 17198556
TI  - [Research on the insulin resistance of islet cells should be strengthened].

PMID- 17198555
TI  - [Indications, surgical strategies and evaluation of prognostic factors in the
      treatment of pulmonary metastases].
AB  - Pulmonary metastases resection is a method universally accepted in selected
      patients. Long-term survival reaches good levels after complete resection of lung
      metastases independently of primary tumour histology. The Authors emphasizes
      literature data; they report data of their experience no statistically
      significant but useful for valuation of results. They discuss of advantages vs
      disadvantages of the surgical procedures. In conclusion they believe
      metastasectomy is a safe treatment of pulmonary metastases.

PMID- 17198557
TI  - [Impairment of fluctuation of blood sugar upon the target organs].

PMID- 17198559
TI  - [Chronic renal disease in diabetic and prediabetic subjects: a community-based
      study in Shanghai].
AB  - OBJECTIVE: The aim of the present study was to assess the prevalence and risk
      factors of chronic renal disease in hyperglycemic population of Shanghai Caoyang
      Community. METHODS: Microalbuminuria was determined by measuring urinary albumin
      to-creatinine ratio (ACR) and glomerular filtration rate (GFR) was estimated from
      fasting serum creatinine. RESULTS: A total of 406 Shanghai Chinese, with the
      average age of 67.5 +/- 13.8 years (244 with diabetes mellitus and 162 with
      impaired glucose regulation) from the established hyperglycemic cohort were
      included. (1) The prevalence of microalbuminuria was 20.9% and 10.5% in the
      subjects with diabetes and impaired glucose regulation (IGR); (2) The prevalence
      of a cGFR >or= 60 and < 90, >or= 30 and < 60, < 30 mlxmin(-1)x(1.73 m(2))(-1)
      were 41.6%, 37.0%, 1.2% respectively in the patients with diabetes, and 34.2%,
      47.2%, 1.9% in the patients with IGR. Impaired renal function was 38.2% and 49.1%
      respectively in the subjects with diabetes and IGR; (3) The prevalence of
      microalbuminuria was significantly higher in the diabetic patients with
      hypertension, central obesity, dyslipidemia, history of cardiovascular disease or
      selinity. Systolic blood pressure, waist circumstance, fasting plasma glucose and
      history of cardiovascular disease were all independently associated with
      hyperglycemic microalbuminuria; (4) cGFR was diminished with increased age and
      the impaired renal function was more frequent in the patients with hypertension
      (48.5%). There was a significant positive correlation between a diminished cGFR
      and increasing levels of ACR after the patients with macroalbuminuria were
      deleted and adjusted age. Serum creatinine, age and systolic blood pressure were
      independently associated with diabetic cGFR < 60 ml/min/1.73 m(2). CONCLUSIONS:
      The high prevalence of microalbuminuria and impaired renal function in the
      hyperglycemic population of Caoyang Community underlines the need for cost
      effective programs for the detection of chronic renal disease, and approaches to
      screen it in the hyperglycemic patients should incorporate assessment of GFR in
      addition to monitoring urine albumin excretion.

PMID- 17198560
TI  - [Decrease of FOXP3 mRNA in CD4+ T cells in latent autoimmune diabetes in adult].
AB  - OBJECTIVE: To study the percentage of peripheral blood CD4(+)CD25(+) T cells and
      the expression of FOXP3 mRNA in the patients with latent autoimmune diabetes in
      adult (LADA). METHODS: Fresh peripheral blood samples were obtained from 60
      patients with LADA, 30 patients with type 2 diabetes and 30 age- and sex-matched
      matched healthy nondiabetic control subjects without diabetic family history. Two
      color staining (anti-CD4, anti-CD25, anti-CD3, and anti-CD8) flow cytometric
      analysis was employed to measure the CD4(+)CD25(+) T cells. The CD4 positive
      human cells were isolated with immunomagnetic beads, and then real time-PCR was
      used to test the expression of FOXP3 mRNA in the CD4(+) T cells. RESULTS: In the
      LADA group, the percentage of CD4(+)CD25(+) T cells was 4.1 +/- 1.9,
      significantly higher than that of the normal control group (2.8 +/- 1.5, P <
      0.01), the ratio of CD4(+)CD25(+) to the CD4(+) T cells was 11.9 +/- 5.0,
      significantly higher than that of the normal control group (8.2 +/- 3.7, P <
      0.01), the percentage CD8(+) T cells was 24.6 +/- 6.8, significantly higher than
      that of the normal control group (19.4 +/- 7.1, P < 0.01) and the CD4(+)/CD8(+)
      ratio was 1.5 +/- 0.5, significantly lower (1.9 +/- 0.6, P < 0.01). The
      expression of FOXP3 mRNA in CD4(+) T cells of the LADA group was 0.52 time that
      of the control group (P < 0.01). The CD4(+)/CD8(+) ratio of LADA group was
      significantly lower that of the type 2 diabetes group (1.8 +/- 0.8, P < 0.05),
      however, the other results were not significantly different between these 2
      groups. The percentage of was positively correlated with the titer of glutamic
      acid decarboxylase antibody (GADA) (r = 0.292, P < 0.05). CONCLUSION: Though the
      percentage of CD4(+)CD25(+) T cells and the level of CD25 expression in CD4(+) T
      cells are elevated, the expression of FOXP3 mRNA in CD4(+) T cells is lower. in
      the patients with LADA. The regulatory T cells may have defective suppressor
      function in patients with LADA.

PMID- 17198561
TI  - [Characteristics of dysfunction of islet beta-cell in newly diagnosed type 2
      diabetic patients].
AB  - OBJECTIVE: To investigate the characteristics of the dysfunction of islet beta
      cell in newly diagnosed type 2 diabetic patients. METHODS: Intravenous glucose
      tolerance test (IVGTT) was carried out on 352 newly diagnosed type 2 diabetic
      patients and 48 subjects with normal glucose tolerance (NGT) and then blood
      samples were collected 1, 2, 4, 6, and 10 minutes later to measure the plasma
      glucose and insulin to calculate the acute insulin response (AIR) and the area
      under the curve of insulin (AUC of insulin), homeostasis model assessment beta
      cell (Homabeta), and Homa IR (insulin resistance). RESULTS: The median AIR of the
      type 2 diabetic patients was -33.7 pmol/L, significantly lower than that of the
      NGT subjects (6962.0 pmol/L, P < 0.001). The median AUC of the type 2 diabetic
      patients was 834.2 pmol/L, significantly lower than that of the NGT subjects
      (7934.7 pmol/L, P < 0.001). When the fasting plasma glucose (FPG) of the type 2
      diabetic patients was above 7.0 mmol/L, the AIR value was remarkably reduced with
      a median level of 317.3 pmol/L, and then subsequently disappeared when the FPG
      was above 9.0 mmol/L. After adjustment of the insulin resistance assessed by HOMA
      IR, the Homabeta of the type 2 diabetic patients was reduced to be 30% that of
      the NGT subjects (3.7 +/- 0.9 vs 5.9 +/- 0.9, P < 0.001). Both the fasting
      proinsulin concentration and the ratio of fasting proinsulin to fasting insulin
      of the type 2 diabetic patients were significantly higher those of the NGT
      subjects (22.6 pmol/L +/- 14.7 pmol/L vs 11.5 pmol/L +/- 7.1 pmol/L, P < 0.001;
      and 30.1% +/- 20.5% vs. 12.1% +/- 9.6%, P < 0.001). CONCLUSION: The dysfunction
      of islet beta-cell in newly diagnosed type 2 diabetic patients is mainly
      represented by the disappearance of AIR and the evident decline of AUC and HOMA
      B, and the decrease of quality of insulin secretion.

PMID- 17198563
TI  - [Clinical characteristics of early-onset type 2 diabetes and risk factors
      associated with its chronic complications].
AB  - OBJECTIVE: To investigate the clinical characteristics of early-onset type 2
      diabetes (EOD) and the risk factors associated with its chronic complications.
      METHODS: A total of 2713 T2DM patients were recruited and divided into two
      groups: early- and late-onset groups EOD group (diagnosed at the age <or= 40) and
      late-onset type 2 diabetes (LOD) group (diagnosed at the age > 40). The clinical
      characteristics were compared between two groups, and the risk factors were
      analyses within the early-onset group. RESULTS: (1) The EOD patients were
      characterized by significantly higher levels of triglycerides (2.5 +/- 2.4 mmol/L
      vs 1.9 +/- 1.5mmol/L, P < 0.01) and BMI (24.4 kg/m(2) +/- 4.6 kg/m(2) vs 23.6
      kg/m(2) +/- 3.7 kg/m(2), P < 0.01), higher rates of smoking (29.2% vs 22.0%, P <
      0.01), family history of diabetes (28.6% vs 13.1%, P < 0.01), and higher
      prevalence of metabolic syndrome (18.9% vs 10.7%, P < 0.01), higher proportion of
      patients with unacceptable HbA1c (>7.0%) (77.3% versus 72.7%, P < 0.05) and
      fasting blood glucose >or= 7.0 mmol/L, (80.8% versus 74.6%, P < 0.05). (2) The
      prevalence rates of microvascular complications were higher than those of
      macrovascular complications in the EOD group, and the prevalence rates of pain,
      anesthesia, diarrhea, and nephropathy were 10.6%, 6.20%, 6.00%, and 13.00%
      respectively, all significantly higher than those of the LOD group (7.10%, 2.80%,
      3.70%, and 8.00% respectively, P < 0.05, < 0.01, < 0.05, and < 0.01). Linear
      regression analysis showed that certain subsets of chronic complications were
      associated with onset age, diabetes duration, hypertension, family history and
      high level of triglyceride. CONCLUSION: Early-onset DM patients present the
      clinical features of poorer metabolic profiles, which may contribute to the
      development of certain subsets of microvascular complications. Late-onset
      patients tend to be complicated with macrovascular diseases, such as
      cerebrovascular disease, angiocardiopathy, etc. Multiple factor comprehensive
      control is important for the prevention of the complications.

PMID- 17198562
TI  - [The expression of insulin signal transduction molecules and islet alpha cell
      insulin resistance].
AB  - OBJECTIVE: To study the changes of insulin signal transduction molecules in islet
      alpha cells in high-fat-diet plus beta cell-deleting rat models and its
      underlying mechanism. METHODS: Thirty SD rats were randomly divided into 2 equal
      groups and fed with high-fat-diet (HF group) or normal diet (normal control
      group, NC group) respectively. At the end of twenty-week feeding, the fasting
      serum insulin (Ins), glucagon (Glc), free fatty acid (FFA), and triglyceride (TG
      were measured. The glucose infusion rate (GIR) was measured by using euglycemic
      hyperinsulinemia clamp to evaluate the peripheral insulin resistance. At the same
      time, large dose streptozocin (100 mg/kg) was injected so as to establish beta
      cell-deleting rat models, i.e., HF-B group (n = 8) and NC-B group (n = 8). Five
      days later, the rats of the HF-B and NC-B subgroups were sacrificed, and the
      pancreatic islets were isolated and collected. The expression of Glc, insulin
      receptor substrate-1 (IRS-1), IRS-2, and phosphatidylinositol-3-kinase (PI3K)
      gene in the islets were detected by RT-PCR. RESULTS: (1) The serum FFA, insulin
      and Glc concentrations of the HF group were 508 (394 - 622) micromol/L, 23.7
      (14.0 - 33.4) mIU/L, and 345 (298.6 - 391.4) pg/ml respectively, all
      significantly higher than those of the NC group [325 (240 - 410) micromol/L, 11.5
      (3.6 - 19.4) mIU/L, 256 (226.4 - 285.6) pg/ml; respectively, all P < 0.05]. The
      GIR of the HF group was 5.25 mgxmin(-1)xkg(-1) +/- 1.2 mgxmin(-1)xkg(-1),
      significantly lower than that of the NC group (13.6 mgxmin(-1)xkg(-1) +/- 1.7
      mgxmin(-1)xkg(-1), P < 0.01)). (2) The gene expression of Glc of the HF-B
      subgroup was significantly higher than that of the NC-B subgroup by 34.2% +/-
      2.1%. In contrast, the expression of IRS-2, and PI3K of the HF-B subgroup was
      significantly lower than that of the NC-B subgroup by 28.5% +/- 1.8% and 21.3% +/
      1.6% respectively (both P < 0.01). (3) The plasma FFA concentration was
      asignificantly negatively correlated with GIR (r = -0.675, P < 0.05) and IRS-2
      gene expression in islet alpha cells (r = -0.458, P < 0.05) in the HF-B group.
      CONCLUSION: High-fat-diet feeding plus beta cell-deleting rat model shows an
      impaired expression of insulin signal transduction molecules in islet alpha cells
      which may relate with the increased plasma FFA concentration.

PMID- 17198564
TI  - [Effect of emodin on pancreatic fibrosis: experiment with rats].
AB  - OBJECTIVE: To study the effect of emodin on pancreatic fibrosis and potential
      mechanism thereof. METHODS: Fifty SD rats were randomly divided into 5 equal
      groups: normal control group, model control group, low-dose emodin-treated group,
      mediate-dose emodin-treated group, and high-dose emodin-treated group. The rats
      of the latter 4 groups underwent infusion of trinitrobenzene sulfonic acid (TNBS)
      into the pancreatic duct so as to establish models of pancreatic fibrosis. The
      emodin-treated rats were fed with different doses of emodin (20, 40, and 80 mg/kg
      body weight), while the normal and model control groups received 0.9% sodium
      chloride solution instead. Twenty-eight days later the rats were killed, blood
      samples were collected, and their pancreases were taken out. The serum levels of
      hyaluronic acid (HA) and laminin (LN) were determined by radioimmunoassay. The
      histopathological alterations were studied by optical microscopy. The expression
      of collagen was examined by Van Gieson staining. Western blotting was used to
      detect the protein expression of transforming growth factor-beta(1) (TGF
      beta(1)). RESULTS: (1) The serum level of HA of the low-dose, mediate-dose, and
      high-dose emodin-treated groups were 87 microg/L +/- 22 microg/L, 78 microg/L +/-
      25 microg/L, and 62 microg/L +/- 19 microg/L respectively, all significantly
      lower than that of the model control group (113 microg/L +/- 27 microg/L, P <
      0.05 or < 0.01). The serum levels of laminin in the low-dose, mediate-dose, and
      high-dose emodin-treated groups were 67 microg/L +/- 14 microg/L, 57 microg/L +/-
      12 microg/L, and 44 microg/L +/- 10 microg/L respectively, all significantly
      lower than that of the model control group (86 microg/L +/- 17 microg/L, P < 0.05
      or P < 0.01); (2) The degrees of fibrosis of the emodin-treated groups were
      obviously ameliorated in comparison with the model control group, the higher the
      dose of emodin the more improved the pathological changes, especially in the high
      dose emodin-treated group (P < 0.05). (3) The percentages of collagen positive
      cells of the low-dose, mediate-dose, and high-dose emodin-treated groups were 39%
      +/- 7%, 38% +/- 4%, and 36% +/- 5% respectively, all lower than that of the model
      control group (42% +/- 6%), with a significant difference between the high-dose
      emodin-treated group and the model control group (P < 0.05). (4) The protein
      content of TGF-beta(1) of the low-dose, mediate-dose, and high-dose emodin
      treated groups were 44.3% +/- 2.1%, 39.2% +/- 1.8%, and 28.8% +/- 1.6%
      respectively, all significantly lower than that of the model control group (60.7%
      +/- 1.7%, all P < 0.05), and the protein content of TGF-beta(1) of the high-dose
      emodin-treated group was significantly lower than those of the other 2 emodin
      treated groups (both P < 0.05). CONCLUSION: Emoidn has an anti-fibrosis effect on
      pancreatic fibrosis, which maybe related to the content of TGF-beta(1) protein.

PMID- 17198565
TI  - [The clinical significance of expression and amplification of FGF3 in bladder
      transitional cell carcinoma].
AB  - OBJECTIVE: To investigate the amplification and expression of FGF3 in bladder
      transitional cell carcinoma (BTCC) and its clinical significance. METHODS:
      Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) methods
      were used to examine the protein expression and amplification of FGF3 in a tissue
      microarray (TMA) of 100 BTCCs and 30 adjacent normal bladder mucosas, so as to
      analyze their correlation and association with patient's clinico-pathological
      features. RESULTS: In this study, none of the normal bladder mucosas were
      detected FGF3 positivity, while in 89 informative BTCCs, 20 (22%) cases were
      observed positive expression of FGF3 protein, and it was significantly more
      frequently to occur in BTCCs of poor-differentiation (Grade 3), later clinical
      stage (T2-4) and tumor in >or= 3 cm in diameter (P < 0.05). In FISH study, 10 of
      the 63 (16%) informative BTCCs were observed amplification of FGF3 and it was
      significantly associated with BTCC's tumor size and clinical stage (P < 0.05). In
      addition, 10 BTCCs with amplification of FGF3 in this study were all detected
      positive expression of FGF3 protein, while in the remaining 53 BTCCs without
      amplification of FGF3, only 3 (6%) cases were observed FGF3 protein positivity.
      CONCLUSION: The up-regulated expression of FGF3 in BTCC was associated closely
      with tumor's malignant clinical phenotypes, and it might be involved in the
      malignant progression of parts of BTCC. The amplification of FGF3 gene might be a
      predominant mechanism of increased expression of FGF3 protein in BTCC.

PMID- 17198566
TI  - [Transurethral holmium laser enucleation of the prostate for the treatment of
      benign prostatic hyperplasia].
AB  - OBJECTIVE: To evaluate the efficacy and safety of transurethral holmium laser
      enucleation of the prostate (HoLEP) for the treatment of benign prostatic
      hyperplasia (BPH). METHODS: A retrospective review was conducted of transurethral
      (HoLEP) performed on 68 patients, aged 65.7 (50 - 91) with benign prostatic
      hyperplasia. The efficacy and complications were all assessed. RESULTS: The mean
      procedure time was 87 mins (45 - 158 mins). The mean specimen weight was 61 g (31
      - 128 g). The procedure allows a precise, bloodless field with no need for
      transfusion. No TUR syndrome and other major complications were encountered
      during the operation. The mean catheter time and hospital stay were 2.8 d (1 - 4
      d) and 3.6 d (2 - 5 d), respectively. Follow-up of 7.6 months (1 - 13 months)
      revealed that the urination symptoms were markedly improved in all patients, and
      that the IPSS decreased from 25.7 +/- 6.9 to 7.7 +/- 4.3 (P < 0.01) and the
      maximum urine flow rate increased from 8.1 +/- 4.2 ml/s to 18.8 +/- 4.6 ml/s (P <
      0.01). Postoperative complications occurred in 3 patients. 2 with transient
      incontinence were recovered within 3 months postoperatively. The other one with
      mild posterior urethral stricture was treated effectively with urethral sounding.
      CONCLUSIONS: Was associated with high effectiveness, safety, short hospital stay
      and less complications, HoLEP is a new minimally invasive surgical procedure for
      BPH.

PMID- 17198580
TI  - [It is the right time to put attention to the basic research of lung cancer].

PMID- 17198581
TI  - [To develop stroke rehabilitation widely and in depth in China].

PMID- 17198567
TI  - [Inhibitory effects of silymarin on hepatic fibrosis induced by
      dimethylnitrosamine: experiment with rats].
AB  - OBJECTIVE: To investigate the antifibrotic effects of silymarin on hepatic
      fibrosis. METHODS: Sixty-one male Wistar rats were randomly divided into three
      groups: control group (15 rats); DMN model group (23 rats), injected
      intraperitoneally with dimethylnitrosamine (DMN) 10 mg/kg twice per week for 8
      weeks to induce hepatic fibrosis; and silymarin group (23 rats), injected
      intraperitoneally with DMN and given silymarin 50 mg/kg by gastric gavage daily
      for 8 weeks. Eight weeks late all rats were sacrificed. Blood samples were
      collected to measure the alanine transaminase (ALT), aspirate aminotransferase
      (AST), albumin, and total bilirubin (TBIL). The hydroxyproline (Hyp) content in
      the liver tissue was measured. The histopathological changes as well as the
      fibrosis stages and score were examined by microscopy. RESULTS: The levels of
      ALT, AST, and TBIL of the silymarin groups were 59 U/L +/- 19 U/L, 159 U/L +/- 39
      U/L, and mean rank 24 respectively, all significantly lower than those of the DMN
      model group (128 U/L +/- 25 U/L, 246 U/L +/- 61 U/L, and mean rank 37
      respectively, P < 0.01, P = 0.001, and P = 0.003). Compared with DMN rats, the
      level of Hyp of the silymarin was lower by 42.6%, the hepatic score of the
      silymarin was 6.2 +/- 2.4, significantly than that of the DMN model group (12.8
      +/- 4.4, P = 0.001), and more cases in the silymarin group were at the lower
      stages. CONCLUSION: Silymarin markedly inhibits and reverse the progression of
      hepatic fibrosis induced by dimethylnitrosamine.

PMID- 17198582
TI  - [Molecular target therapy: a new method in treatment of lung cancer].

PMID- 17198583
TI  - [Chinese health resource distribution principles reflected by rank of death rate
      of respiratory diseases in two decades].

PMID- 17198584
TI  - [Relationship of the curative effects of gefitinib on non-small cell lung
      carcinoma to gender and to epithelial growth factor receptor status].
AB  - OBJECTIVE: To investigate the mutation of epithelial growth factor receptor
      (EGFR) gene in the non-small cell lung carcinoma (LSCLG) patients with different
      genders and the relationship between the gender of LSCLG patients and the
      curative effects of gefitinib, an specific tyrosine kinase. METHODS: Tumor
      specimens were obtained from 135 NSCLC patients, 94 males (78.7% smoking) and 41
      females (17.1% smoking), of which 20 received gefitinib treatment after the
      failure of chemotherapy, during operation and stored at -80 degrees C. The
      genomic DNA of the cancer tissues was extracted by using Trizol reagent. Nest-PCR
      was used to amplify the exons 18, 19, and 21 of the EGFR gene and the PCR
      products were purified by agarose electrophoresis and then sequenced. RESULTS:
      EGFR mutation was found in 29 of the 135 NSCLC patients (21.5%), with a mutation
      rate of 19.1% in the males and a mutation rate of 26.8% in the females (P =
      0.344). The mutation types included G719C and G719V in exon 16, delE746 - 750,
      and delE746 - 751 in exon 19, and L858R and L861Qin exon 21. Among the 20
      patients who received gefitinib treatment the disease control rate was 85%
      (17/20), being 76.9% in the male patients (10/13) and being 100% in the female
      patients (7/7) (P = 0.521). There were not significant differences in the mean
      time-to-progression (TTP) between the male and female patients (9 months vs. 14
      months, P = 1), and between the patients with the wild type of EGFR gene and
      those with the mutated type of gene (9 months vs. 14 months, P = 1). CONCLUSION:
      There is no significant relationship between the curative effect of gefitinib on
      NSCLC and gender and EFGR status.

PMID- 17198586
TI  - [Influences of PC cell-derived growth factor and breast cancer resistance protein
      on the curative effects of platinum-based chemotherapeutic regimens for advanced
      non-small cell lung cancer].
AB  - OBJECTIVE: To investigate the influences of PC cell-derived growth factor (PCDGF)
      and breast cancer resistance protein (BCRP) on the curative effects of platinum
      based chemotherapeutic regimens for advanced non-small cell lung cancer (NSCLC).
      METHODS: Specimens of cancer were collected from 87 chemotherapy-naive patients
      with advanced NSCLC, 61 males and 26 females, aged 42 - 75. Immunohistochemistry
      was used to examine the expression of PCDGF and BCRP. After the collection of
      pathological specimens the patients underwent platinum-based chemotherapy. The
      relationship between the expression of PCDGF and BCRP and the curative effects of
      chemotherapy was analyzed. RESULTS: The overall response rate (OR) to
      chemotherapy of the 87 patients was 41.38% (36/87), 36 of the patients were
      chemosensitive (41.38%), and the other 51 were chemoresistant (58.62%). Forty-six
      of the 87 patients (52.9%) were PCDGF positive, the PCDGF positive rate of the
      chemoresistant patients was 74.5%, significantly higher than that of the
      chemosensitive patients (19.4%, P = 0.000). The patients with high PCDGF
      expression intensity were all chemoresistant. PCDGF expression was significantly
      associated with response of chemotherapy (P = 0.000). The overall positive BCRP
      expression rate was 67.82% (59/87). Of the 51 chemoresistant patients 46 were
      BCRP positive (90.2%), a rate significantly higher than that of the
      chemosensitive patients (36.1%, P = 0.000). The intensity of BCRP expression was
      significantly associated with response to chemotherapy (P = 0.000). CONCLUSION:
      PCDGF and BCRP may be used as biomarkers to predict the first-line response to
      chemotherapy in patients with advanced NSCLC.

PMID- 17198587
TI  - [A meta-analysis of the curative effects of carboplatin-based and cisplatin-based
      chemotherapeutic regimens on advance non-small cell lung cancer].
AB  - OBJECTIVE: To evaluate whether there is a difference in the curative effect of
      carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non
      small cell lung cancer (NSCLC). METHODS: The databases PudMed, CENTRAL, and
      Chinese biomedical database were retrieved by using the key words "non-small cell
      lung cancer" or "carcinoma, non-small cell lung" so as to search the materials
      about the randomized controlled clinical trials that had compared the curative
      effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on
      advance NSCLC. A meta-analysis was conducted. RESULTS: Eighteen documents about
      randomized controlled clinical trials, including 6478 patients, from the
      retrieved 3531 documents accorded to the demand of enrollment. The overall
      response rates of the carboplatin-based and cisplatin-based chemotherapeutic
      groups were both 27% (RR = 0.93, 95% CI = 0.86 approximately 1.01, P = 0.10).
      Neither funnel plot nor rank correlation test regarding response rate indicated
      the existence of publication bias (chi(2) = 18.63, P = 0.63). The 0ne-year
      survival rate of the carboplatin-based regimen group was 36%, not significantly
      different from that of the cisplatin-based regimen group (35%, RR = 1.04, 95% CI
      = 0.93 - 1.17, P = 0.5). Sensitive analysis confirmed the non-existence of
      differences in the overall response rate and one-year survival rate between these
      2 groups. CONCLUSION: The curative effects of the carboplatin-based and cisplatin
      based chemotherapeutic regimens are similar. The choice of carboplatin or
      cisplatin depends on the toxicity of the drugs and the patients' tolerance.

PMID- 17198588
TI  - [Effects study of standardized tertiary rehabilitation on promoting of the
      neurological functions in stroke patients with hemiplegia].
AB  - OBJECTIVE: To investigate the effects of standardized tertiary rehabilitation
      (STR) on promotion of the neurological functions in stroke patients with
      hemiplegia. METHODS: A large-sample, multi-center, randomized, controlled
      prospective study was conducted nationwide. 1209 stroke patients with hemiplegia,
      aged 40 - 80, within 11 d +/- 5 d after the onset, stabilized in vital life signs
      in the past one week, of 20 hospitals affiliated to medical colleges or of
      hospitals at the provincial level in mainland China were randomly allocated to
      one of the 2 baseline data-matched groups: control group (n = 599, 446 with
      cerebral infarction and 153 with cerebral hemorrhage) receiving routine
      intervention of internal medicine, and STR group (n = 610, 455 with cerebral
      infarction and 155 with cerebral hemorrhage), receiving routine intervention and
      STR including physical therapy and occupational therapy (OT) in addition.
      Evaluation was conducted by the time of enrollment, and by the ends of the first,
      third, and sixth months by the national clinical neurological function defects
      (CNFD) scoring. RESULTS: There were no significant differences in the baseline
      indexes between these 2 groups. The scores of CNFD at enrollment of the patients
      with cerebral infarction in the STR group was 21.55, not significantly different
      from that of the patients with cerebral infarction in the control group (22.16),
      however, the scores of these patients with cerebral infarction in the STR group
      by the ends of the first, third, and sixth months were 16.32, and 11.48, and 8.63
      respectively, all significantly lower than those of the corresponding patients in
      the control group (18.95, 15.57, and 13.78 respectively, all P < 0.01). The CNFD
      score at enrollment of the patients with cerebral hemorrhage in the STR group was
      23.27, not significantly different from that of the corresponding patients in the
      control group (24.36), however, the scores of the patients with cerebral
      hemorrhage in the STR group by the ends of the first, third, and sixth months
      were 17.61, 11.20, and 7.95 respectively, all significantly lower than those of
      the corresponding patients in the control group (20.36, 15.01, and 13.57
      respectively, all P < 0.01). By the end of the sixth month, the CNFD score of the
      cerebral infarction and hemorrhage patients in the STR group were improved by
      12.79 and 15.23, both higher than the corresponding patients in the control group
      (8.30 and 10.65 respectively). The trend of decrease of CNFD score moved faster
      in the STR group than in the control group, especially at the early stage.
      CONCLUSION: STR significantly helps improved the neurological function in the
      patients with cerebral stroke accompanied with hemiplegia.

PMID- 17198589
TI  - [Effects of functional electrical stimulation on the improvement of motor
      function of patients with acute stroke: a randomized controlled trial].
AB  - OBJECTIVE: To investigate the effects of functional electrical stimulation (FES)
      on the improvement of motor and walking ability of the lower extremities of the
      patients with acute stroke. METHODS: Forty-six patients with stroke (including
      cerebral infarction and hemorrhage), aged 71 +/- 8 (45 - 84), hospitalized within
      2 weeks (9 +/- 4 days) after the onset, matched with one another in the baseline
      measurements before treatment, were assigned randomly into 3 groups: FES group (n
      = 13), receiving standard rehabilitation combined with FES 30 minutes per day, 5
      days per week for 3 weeks, placebo stimulation group (n = 15) receiving standard
      rehabilitation combined with the installment of the FES apparatus, operated in
      the same manner as mentioned above, however, without real electric stimulation,
      and control group (n = 13), receiving standard rehabilitation alone. The score of
      the composite spasticity scale (CSS) was measured, electromyography was conducted
      to measure the maximum isometric voluntary contraction (MIVC) of the ankle dorsi
      flexors and plantar-flexors, and walking ability by the test of timed "Up and Go"
      before treatment, weekly during the 3-week treatment, and 8 weeks after the onset
      of stroke. RESULTS: After 3 weeks of treatment, the percentage of CSS score of
      the FES group was 31% +/- 35%, significantly lower than those of the placebo and
      control groups (50% +/- 88% and 65% +/- 65% respectively, both P < 0.05); the
      ankle dorsiflexion torque of MIVC of the FES group was 9 Nm +/- 5 Nm,
      significantly higher than those of the placebo and control groups (5 Nm +/- 3 Nm
      and 4 Nm +/- 5 Nm respectively, both P < 0.05), and the electromyogram co
      contraction ratio of the FES group was 8% +/- 5%, significantly lower than those
      of the placebo and control groups (27% +/- 26% and 28% +/- 19% respectively, both
      P < 0.05). The time needed to recover the walking ability after the stroke onset
      of the FES group was 18 +/- 8 days, shorter by 2 approximately 3 days than those
      of the placebo and control groups (20 +/- 7 and 21 +/- 8 days respectively). The
      percentage of the patients able to walk with the help of a stick 3 weeks after
      treatment of the FES group was 85%, significantly higher than those of the
      placebo and control groups (60% and 46% respectively, both P < 0.05). 84.6% of
      the patients of the FES group returned home, a percentage significantly higher
      than those of the placebo and control groups (53% and 46% respectively, both P <
      0.05). CONCLUSION: FES, plus standard rehabilitation, is effective in improving
      the motor and walking ability of the patients with acute stroke, to the degree
      that most patients are recovered to be able to return home.

PMID- 17198590
TI  - [Mechanism of post-stroke reflex sympathetic dystrophy: study with needle
      electromyography].
AB  - OBJECTIVE: To explore the mechanism of post-stroke reflex sympathetic dystrophy
      (RSD) patients electromyographic abnormality and confirm its clinical value.
      METHODS: Fifty patients with first-onset stroke, aged 33 - 78, including 30 with
      RSD and 20 without RSD, underwent needle electromyography (EMG) to test the nerve
      conduction velocity (NCV) and sensory nerve conduction velocity (SCV) of
      bilateral median nerves, and the number and position of spontaneous EMG activity
      of bilateral short abductor muscles of thumb and abductor muscles little finger.
      RESULTS: The median nerve compound muscle action potential (CMAP) amplitude of
      the affected upper extremities of the RSD group was 8.6 mV +/- 2.9 mV,
      significantly lower than that of the non-RSD group (13.2 mV +/- 4.6 mV, P <
      0.01). The incidence of spontaneous electrical potential of the RSD group was
      100%; significantly higher than hat of the non-RSD group (65%, P < 0.001). The
      quantity of spontaneous EMG activity on the short abductor muscles of thumb and
      abductor muscles little finger was increased in the RSD group (P < 0.01). The
      motor nerve conduction velocity and electrophysiological presentation of sensory
      nerve of these 2 groups were all normal and without significant differences
      between them. CONCLUSION: Partial axonal degeneration occurs on the distal motor
      never fibers of the affected upper extremity of the RSD patients, which may be
      related to subsequent peripheral nerve injury after central nerve system
      impairment.

PMID- 17198591
TI  - [Effectiveness of backward walking treadmill training in lower extremity function
      after stroke].
AB  - OBJECTIVE: To examine the effectiveness of backward walking treadmill training
      for restoration of motor function, balance and walking speed in patients with
      stroke. METHODS: Twenty-six patients with stroke, 17 males and 9 females, aged 36
      - 64, with the lower extremity Brunnstrom motor recovery stage at 3 or 4, able to
      walk for 10 m without walking aid or orthosis, were randomly divided into two
      equal groups: The patients in the control group were to participate in a 60
      minutes conventional training five times a week for three weeks, and the patients
      in the experimental group received 30-minute conventional training and then 30
      minute backward walking training five times a week for three weeks. Before the
      training and 3 weeks after the training, Fugl-Meyer assessment was used to assess
      the motor function of the lower extremity (FMA-L), Berg balance scale (BBS) was
      used to assess the balance function, and 10 m maximum walking speed was measured.
      RESULTS: After the three-week training period, the FMA-L score of the
      experimental group was 28.0 +/- 3.3, significantly higher than that of the
      control group (25.5 +/- 2.3, P = 0.033); the BBS score of the experimental group
      was 51.4 +/- 1.8, significantly higher than that of the control group (47.3 +/-
      3.7, P = 0.001, and 10 m MWS of the experimental group was 57 +/- 17,
      significantly higher than that of the control group (43 +/- 16, P = 0.034).
      CONCLUSION: A safe and feasible intervention, additional backward walking therapy
      helps improve the damaged motor function, balance, and walking speed of the
      patients with stroke.

PMID- 17198592
TI  - [Effects of transcranial magnetic stimulation on recovery of neural functions and
      changes of synaptic interface and dendritic structure in the contralateral brain
      area after cerebral infarction: experiment with rats].
AB  - OBJECTIVE: To evaluate the effects of transcranial magnetic stimulation (TMS) on
      the brain plasticity and its role in functional outcome in cerebral infarction.
      METHODS: Twenty male SD rats underwent suture of the unilateral middle cerebral
      artery (MCA) so as to establish focal cerebral infarction models and then were
      randomly divided into 2 equal groups: model group, to be reared in the original
      living state, and TMS group, given in addition TMS treatment 1 day after
      infarction 2 times per day and 30 pulses per time for 4 weeks. Twenty-eight days
      after the rats were killed. Four rats from each group underwent microscopy of the
      brain to measure the dendritic structure of the pyramidal cells quantitatively.
      Other 4 rats from each group underwent electron microscopy of the brain to
      measure the parameters of synaptic interface in the sensorimotor cortex. Neural
      function scoring was conducted 24 hours after the establishment of model and
      before being killed. RESULTS: There was no significant difference in the neural
      function 24 h after the establishment of models, however, 28 days after the score
      of neural function of the TMA group was 0.58 +/- 0.49, significantly lower than
      that of the model group (0.92 +/- 0.28, P < 0.05). The total dendritic length,
      number of dendritic branching points, and dendritic density in layer V pyramidal
      cells within the undamaged motor cortex of the TMS group were 898 microm +/- 127
      microm, 6.6 +/- 1.5, and 0.75/microm +/- 0.19/microm, all significantly higher
      than those of the model group (788 microm +/- 112 microm, 5.8 +/- 1.5, and
      0.60/microm +/- 0.16/microm, P < 0.05 or < 0.01). Electron microscopy showed that
      the synaptic curvatures and post-synaptic density of the TMS group were 1.06 +/-
      0.08 and 64 +/- 13 respectively, both significantly higher than those of the
      model group (1.02 +/- 0.06 and 54 +/- 12 nm respectively, P < 0.05 and P < 0.01),
      and the synapse cleft width of the TMS group was 19.5 +/- 2.1, significantly
      narrower than that of the model group (23.3 +/- 2.3, P < 0.01). CONCLUSION: TMS
      promotes the improvement of neural functions of the rats with cerebral ischemia
      by the potential mechanism that TMS strengthen the compensatory roles of the
      synaptic interface and dendritic structure in the undamaged sensorimotor cortex
      area and increase synaptic plasticity.

PMID- 17198602
TI  - [Uncertainty in family medicine and decision-taking shared with the patient].

PMID- 17198603
TI  - [The MIR exam and family doctor jobs].

PMID- 17198604
TI  - [Cost of caring for the diabetic-hypertensive patient in primary care].
AB  - OBJECTIVE: To determine the cost of caring for the diabetic-hypertensive patient
      in primary care. DESIGN: A cost analysis carried out in family medicine units in
      Mexico. SETTING: Family medicine units in Mexico. PARTICIPANTS: Patients with
      diabetes and hypertension. MEASUREMENTS: Include the profile of use of the
      services and the cost of the care. The profile is defined as the average annual
      use of primary care services, the unit cost is calculated by reason for use in
      each of the services used, taking the fixed and variable consumables into
      account; the average cost by reason for care is calculated from use-cost ratio
      and the mean annual cost from the total average cost by reason for the care.
      RESULTS: The mean annual cost in the family doctor clinic was euro180.65 (95%
      confidence interval [CI], 168.31-193), in the laboratory, euro48.99 (95% CI,
      44.85-53.18), and in the rest of the primary care services, euro41.33 (95% CI,
      30.19-52.46). The mean annual primary care cost per patient was euro271 (95% CI,
      243.36- 298.65). CONCLUSION: The primary care costs of the diabetic-hypertensive
      patient are concentrated in the family doctor and laboratory services.

PMID- 17198605
TI  - [Diabetes and hypertension: a growing and costly epidemic].

PMID- 17198606
TI  - [New proposals for evaluating burnout. The specific evaluation of professional
      medical burnout].
AB  - OBJECTIVE: To introduce the development and validation of the Medical
      Professional Burnout Syndrome Scale belonging to the Questionnaire on Medical
      Professional Burnout (QMPB). DESIGN: Descriptive and transversal study in two
      stages. Stage 1: analysis of the psychometric properties of the new questionnaire
      dealing with its construction validity (exploratory factorial analysis, internal
      consistency, and confirmatory factorial analysis). Stage 11: study of its
      convergent validity with the Maslach Burnout Inventory (MBI). SETTING AND
      PARTICIPANTS: Community of Madrid, Spain. Stage I: 485 doctors (primary care
      centres and hospitals). Stage II: new sample of 100 doctors (primary care
      centres). MAIN MEASUREMENTS: Professional burnout through the Medical
      Professional Burnout Syndrome Scale and the Maslach Burnout Inventory. RESULTS:
      The exploratory and confirmatory factorial analysis of the QMBP confirmed 3
      factors that described medical professional burnout: Exhaustion, Distancing, and
      Loss of Hope, with an acceptable internal consistency. Convergent validity was
      confirmed with the MBI, especially in the Exhaustion dimension. CONCLUSIONS:
      Evaluation of psychometric properties confirmed the Medical Professional Burnout
      Syndrome Scale as a valid and specific instrument for studying burnout.

PMID- 17198607
TI  - [Analysis of short-term time off of health workers in a health area].
AB  - OBJECTIVE: To describe the characteristics of short-term time off work (STT):
      duration, causes and distribution by age, and sex. DESIGN: Descriptive,
      observational study. SETTING: Area 1, Madrid, Spain. PARTICIPANTS: Health workers
      with STT in Area 1, Madrid, during the first 6 months of 2003. MAIN MEASUREMENTS:
      The variables studied were: date of start and finish of STT, its duration, its
      cause (ICD-9), age, and sex. RESULTS: Four-hundred eighteen health workers
      (3.7%), with a mean age of 32.7+/-20 years old and 78.79% women. Respiratory
      pathology was the most frequent cause of STT (38%) in both sexes and in all age
      groups, except in the youngest (<25), in whom bone and muscle pathology was more
      common. In decreasing order of frequency appeared bone and muscle pathology
      (26%), infections (13%), and mental illness (10%). The average duration of STT
      was 38.8+/-88.7 days. There was a statistically significant relationship between
      the duration of STT and its cause. Respiratory pathology was the shortest (8.85;
      95% CI, 6.54-11.17) and mental illness, the longest (153.8; 95% CI, 87-220.75).
      The age group with most STT (37-45 years old) had a mean length of STT lower
      (26.93; 95% CI, 16.34-37.51) than the oldest age group (>56), which had less, but
      longer-lasting STT (57.18; 95% CI, 10.74-103.63), though this was not
      statistically significant. CONCLUSIONS: The pathology causing STT is the factor
      that most determines STT's duration. Its prevention would be the best way of
      managing STT.

PMID- 17198608
TI  - [Seven or ten days? Cost-effectiveness study on the duration of H. pylori
      treatment in primary care].
AB  - OBJECTIVE: To determine through an economic evaluation study whether it is cost
      effective to extend treatment of dyspeptic patients from 7 to 10 days,
      distinguishing between functional dyspepsia, unexamined dyspepsia, and ulcer
      disease. DESIGN: Cost-effectiveness study by means of a decision 3 comparing
      direct costs per patient cured with 2 strategies: a) 7 days treatment versus b)
      10 days. Two-year study in the National Health System. SETTING: Primary care.
      PARTICIPANTS: One-hundred patients with peptic ulcer, functional dyspepsia, or
      unexamined dyspepsia who received treatment for H pylori infection.
      INTERVENTIONS: H pylori eradication treatment with a proton pump inhibitor,
      clarithromycin, and amoxycillin for 7 or 10 days. Measurement variable:
      incremental cost per patient cured. RESULTS: In peptic ulcer patients, the
      incremental cost per patient cured on extending the eradication treatment from 7
      to 10 days was euro147 (95% CI, 121.3-162.7), whereas in patients with functional
      or unexamined dyspepsia, it was -euro39.8 (95% CI, -28.5 to -60.7) and -euro27.3
      (95% CI, -14.92 to -52.72), respectively. The sensitivity analysis showed that
      the efficacy of eradication treatment (7 vs 10) was the factor that most affected
      the stability of the results. CONCLUSIONS: Seven days is the most cost-effective
      duration of the triple therapy for eradicating H pylori in ulcer patients.
      However, 10 days is more cost-effective in functional dyspepsia patients or those
      with no prior endoscope diagnosis.

PMID- 17198609
TI  - [Mental health referrals of patients without diagnosable psychiatric pathology].
AB  - OBJECTIVE: To analyze the characteristics of referral from primary health care to
      mental health of patients with no diagnosable mental disorder. METHODS:
      Consecutively and without exemptions, all persons attending for first-time
      consultation a mental health centre in the course of a year were clinically
      examined. We measured the incidence of conditions not attributable to a mental
      disorder using ICD-10 (Z codes). Information was collected on whose idea it was
      that they attended, and who, how and with what treatment they were referred. In
      addition, data about their social, demographic and clinical characteristics were
      collected. RESULTS: Of the 1004 persons examined, 244 (24.4%) (95% CI, 21.6-27)
      did not meet the ICD-10 diagnosis criteria for mental disorders. They themselves
      or their family tended to request the Z codes (54.5%) (95% CI, 48.3-60.8]. Mental
      health referral was almost always through the PC doctor (95.5%) (95% CI, 92.1
      97.7). Half the patients were already receiving drug therapy under their general
      practitioner before their visit and 20.9% (95% CI, 15.8-26) were referred as
      priority patients. CONCLUSIONS: Our study found that a large number of patients
      with no diagnosable mental disorder at the mental health centre, many of them
      with drug treatment prescribed, were referred. This places a question-mark over
      the function of primary care as a filter for these patients. The population s
      indiscriminate health care demand and the steady increase in treating mental
      health with drugs partially explain this phenomenon.

PMID- 17198610
TI  - [The doctor with three heads].

PMID- 17198611
TI  - [Regulatory strategies for complementary and alternative medicines: towards a
      model for understanding health practices].

PMID- 17198612
TI  - [Family and general medicine in Argentina].

PMID- 17198613
TI  - [Psychological ill-treatment in a sample of women assisted in primary care].

PMID- 17198614
TI  - [Do we inform patients correctly when we prescribe an antibiotic?].

PMID- 17198615
TI  - [Flu vaccination in Spain: we still have not improved].

PMID- 17198617
TI  - [The National Death Index: a largely expected advance in the access to mortality
      data].

PMID- 17198616
TI  - [The evaluation of the quality of pharmaceutical prescription].

PMID- 17198618
TI  - [Our visitors: online activity of Gaceta Sanitaria].

PMID- 17198619
TI  - [Gender systems and/in the Spanish National Health Interview Survey].
AB  - OBJECTIVE: To analyze the Spanish National Health Interview Survey (NHIS) from a
      gender perspective, with special emphasis on gender division of labor. METHOD: We
      analyzed the 2003 Spanish NHIS from the perspective of the levels of gender
      observation, with gender understood as: a) the basis of social norms
      (responsibilities by sex, health risks, and problems related to
      masculine/feminine roles); b) the organizer of the social structure: gender
      division of labor, work overload, vertical/horizontal segregation, time spent in
      activities according to social times, access to resources), and c) a component of
      individual identity (conflicts due to multiple roles, body image dissatisfaction,
      self-esteem, self-perceived recognition of the work performed, assimilation of
      the sexual gender role, sex differences in health conditions). RESULTS: The
      Spanish NHIS is centered on the main provider, referred to in masculine
      grammatical form. Gender division of domestic labor is identified only by a
      general question. When using the concept of main activity for productive or
      reproductive work, the survey requires respondents to evaluate them and select
      only one, thus losing information and hampering analysis of the impact of an
      overload of work on health. Information on time used for reproductive work and
      leisure is not solicited. Assaults (intentional) and accidents (non-intentional)
      are combined in the same question, thus preventing research on gender-related
      violence. CONCLUSIONS: The Spanish NHIS includes the variable of sex, but its
      more descriptive than analytic focus limits gender analysis. The survey allows
      specific circumstances of employment-related inequalities between sexes to be
      measured, but does not completely allow other indicators of gender inequalities,
      such as the situation of housewives or work overload, to be measured.

PMID- 17198620
TI  - [Diagnosis of allergic asthma in allergy and pneumology outpatient clinics].
AB  - OBJECTIVES: To estimate the prevalence of diagnosis of allergic asthma in
      patients with persistent asthma attending allergy or pneumology outpatient
      clinics and to describe the clinical management of asthma in these patients.
      METHODS: Systematic random sampling was used to retrospectively include 382
      patients aged between 12 and 65 years old with a diagnosis of persistent asthma
      (according to GINA criteria) who had attended allergy or pneumology outpatient
      clinics during the previous year. Allergic asthma was defined as the presence of
      sensitization to any common allergen according to the results of specific IgE
      determinations and/or skin tests. Data on the treatment of asthma were gathered.
      RESULTS: Allergy studies were performed in 99.5% of the patients attending
      allergy centers and in 76.5% of those attending pneumology centers. A diagnosis
      of allergic asthma was made in 90.6% (95% CI: 86.5-94.7) and 46.1% (95% CI: 39.0
      53.2), respectively. The prevalence of allergic asthma was highest in young male
      patients with less severe asthma. According to the GINA criteria, 14.1% of
      patients from allergy centres and 23.0% of those from pneumology centers were
      classified as having severe persistent asthma. Twenty-four percent of patients
      attending allergy clinics and 5.7% of those attending pneumology centers received
      bronchodilator treatment exclusively. CONCLUSIONS: Diagnosis of allergic asthma
      was much higher in allergy clinics than in pneumology centres. Although some of
      this difference may be due to more frequent performance of allergy studies in
      allergy clinics, the most probable explanation lies in the differences observed
      in the profiles of patients attending the two types of center.

PMID- 17198621
TI  - Characteristics and trends of newly diagnosed HIV-infections, 2000-2004.
AB  - OBJECTIVE: To describe the characteristics and trends of newly diagnosed HIV
      infections. METHODS: We analysed all newly diagnosed HIV-infections among
      residents of the Canary Islands, Ceuta, La Rioja, Navarre and the Basque Country
      (Spain) between 2000 and 2004. RESULTS: In total, 1,807 HIV-infections -74.4 per
      million inhabitants, per year- were diagnosed. The heterosexual transmission
      category was the most frequent (48.6%), followed by that of homo/bisexual men
      (23.0%) and injecting drug users (IDU) (22.5%). From 2000 to 2004, the rate of
      new diagnoses of HIV infection decreased by 29.8% (p < 0.0001). The rate of
      diagnoses of infections acquired by IDU diminished by 58.5% (p < 0.0001), and the
      rate of infections associated with homo/bisexual practices in men descended by
      33.9% (p = 0.0318). Nevertheless, the rate of diagnoses of infections by
      heterosexual transmission has not undergone significant changes. In the period
      2002-2004, 28.7% of cases were diagnosed in foreigners, but the rate of diagnoses
      in the population of non-Spanish origin diminished by 24% (p = 0.0534). 39.7% of
      HIV diagnoses were delayed (with CD4 < 200 cells/microlitre or coinciding with
      the diagnosis of AIDS). This situation was less frequent in women (odds ratio =
      0.5; p < 0.001) and increased with age amongst people over 30. The proportion of
      delayed diagnoses reached a maximum in 2001 (47.5%) and then declined until 2004
      (38.6%; p = 0.022). CONCLUSIONS: Although none of the analysed indicators evolved
      unfavourably, it is important to insist on the prevention of sexual transmission,
      the early diagnosis of HIV infection, and the need to adapt preventive activities
      and focus them on people from other countries.

PMID- 17198622
TI  - Comment. It is necessary to know who gets HIV infected.

PMID- 17198623
TI  - [A pilot program to improve causes of death certification in primary care of
      Catalonia, Spain].
AB  - OBJECTIVE: The BEDTAR pilot program assessed changes in the quality of
      certification of death's causes after a training session for the primary care
      physicians in the Tarragona's Area of Catalonia, in the Northeast of the Iberian
      Peninsula. DESIGN: Before-after evaluative study with intervention and without
      control group. SETTING AND PARTICIPANTS: The study population was the physicians
      of the reformed primary health care network of the AT. MATERIAL AND METHODS: The
      training session began with a test consisting of certifying 3 deaths. This test
      was followed by a theoretical and practical seminar. The session concluded with a
      final test consisting on certifying the same 3 cases. The variables used to
      evaluate the quality the certification were: logical sequence the death causes,
      correct position on death certificate of the immediate, intermediate and basic
      causes, precise use of cardiac arrest and other ill-defined diseases, appropriate
      use of abbreviations, legibility, vocabulary and, finally, use of all the
      available information. RESULTS: The final participation of the study population
      was 71% and the global program efficacy was 59%. CONCLUSIONS: The BEDTAR program
      improved the quality of certification and emphasized the relevancy and the
      applicability of the results.

PMID- 17198624
TI  - [An approach to "quality-adjusted life years" quality of life weights from self
      assessed health status].
AB  - OBJECTIVES: To estimate quality of life weights in Spain for 1987, 1993 and 2001,
      based on self-assessed health status reported in the National Health Survey.
      MATERIAL AND METHODS: Quality of life weights were estimated using an ordered
      probit model. In this model, self-assessed health status was related to the
      presence of chronic diseases, demographic characteristics, and a random error.
      Quality of life weights were derived by normalizing the regressors obtained.
      RESULTS: Quality of life values related to chronic diseases varied depending on
      the diseases. Pain, limitations, and diseases in the previous 12 months had a
      greater negative impact on quality of life than did chronic diseases. Quality of
      life decreased as age increased, and increased as educational level increased.
      For the same disease and adjusted for age, sex, and educational level, quality of
      life weights were greater for 1993 and 2001 than for 1987. CONCLUSIONS: The
      proposed methodology allows quality of life weights to be calculated from health
      survey data, which has direct application in economic assessment, analysis of
      socioeconomic health inequalities, and health capital estimation.

PMID- 17198625
TI  - [Patients, physicians and nurses: three different points of view on the same
      issue. Attitudes to and perceptions of patient rights].
AB  - OBJECTIVES: To analyze patients', physicians' and nurses' attitudes to and
      perceptions of patient rights in the public hospitals of the Reus health district
      in Catalonia (Spain). METHODS: We performed a qualitative analysis, through focus
      groups composed of health professionals (physicians and nurses) and discharged
      patients, followed by three surveys aimed at physicians, nurses, and patients. A
      descriptive analysis was performed of the results and of the differences among
      the three collectives. A principal components analysis for categorical data was
      used to reduce the number of dimensions and to reveal the associations among the
      different variables. RESULTS: Among discharged patients and nurses, the most
      important patient rights were "the right to information" and "patient autonomy",
      whereas among physicians, the most important dimensions were the "right to
      autonomy" and "the patient's right to form an opinion". A minority of patients
      was reluctant to participate in decision-making. The groups with the most
      favorable attitudes to exercising patient autonomy were women, younger patients,
      and those with the highest educational level. Patients were less in favor of
      patient autonomy than physicians while nurses had the most radical attitudes in
      favor of patient autonomy. CONCLUSIONS: Patient's rights are not sufficiently
      well known, and the right to information is valued more highly than the right to
      exercise autonomy. Discharged patients, physicians and nurses have different
      attitudes to and perceptions of the same issue.

PMID- 17198626
TI  - [Geographical distribution and time trends of suicide mortality in Catalonia and
      Spain [1986-2002]].
AB  - OBJECTIVE: To analyze time trends in Catalonia (1986-2002) and Spain (1986-2001)
      in suicide mortality and its geographical variation by health areas in Catalonia.
      METHODS: Standard annual mortality rates were calculated by the direct method for
      Catalonia (1986-2002) and Spain (1986-2001) (standard population of Catalonia
      1991). The adjusted annual percent change was analyzed by means of a Poisson
      regression by gender and by age group for Catalonia and Spain. For the
      geographical variation in Catalonia, standardized mortality ratio using the
      indirect method (SMR) were calculated by gender and for the 46 health areas for
      the entire period and the comparative mortality figures and its confidence
      intervals at 95% were analyzed grouping the years in period 1(1986-1994) and
      period 2 (1995-2002). RESULTS: Men's mortality in Catalonia was lower than in
      Spain and an increase (not significant) was observed in both places during the
      period; for women, the evolution and rates were similar, with a small decrease
      (significant) for Catalonia and Spain. Differences in patterns and trends for age
      and sex were observed, showing a decrease in the elderly groups for both sexes
      and an increase for the young for Spain and Catalonia. In terms of geographic
      distribution, the health sectors of the Central, Northeast and South Catalonia
      zones show higher than average mortality. CONCLUSIONS: The time trends of
      mortality by suicide in Catalonia shows different patterns according to age and
      gender. A progressive homogenization in the territorial distribution by health
      areas was observed.

PMID- 17198627
TI  - [Mortality and morbidity from disasters in Spain].
AB  - OBJECTIVE: To analyze disaster episodes in Spain between 1950 and 2005 in order
      to characterize their pattern and evaluate their impact on morbidity and
      mortality. METHODS: We performed an observational retrospective study using the
      United Nations' definition of disaster. A disaster was considered as each
      episode, natural or technological, causing more than 15 deaths and/or more than
      50 wounded persons. Epidemic and environmental disasters were excluded. RESULTS:
      The frequency of disasters has increased in Spain, especially during the four
      last decades. The frequency of disasters doubles in the second semester of the
      year and shows wide geographical variation. Spain has a mixed disaster pattern,
      with a predominance of technological disasters, which are 4.5 times more frequent
      than natural disasters. The most frequent type of natural disaster in Spain is
      flooding and most frequent technological disasters are traffic accidents.

PMID- 17198628
TI  - [Coordination among healthcare levels: systematization of tools and measures].
AB  - Improving healthcare coordination is a priority in many healthcare systems,
      particularly in chronic health problems in which a number of professionals and
      services intervene. There is an abundance of coordination strategies and
      mechanisms that should be systematized so that they can be used in the most
      appropriate context. The present article aims to analyse healthcare coordination
      and its instruments using the organisational theory. Coordination mechanisms can
      be classified according to two basic processes used to coordinate activities:
      programming and feedback. The optimal combination of mechanisms will depend on
      three factors: the degree to which healthcare activities are differentiated, the
      volume and type of interdependencies, and the level of uncertainty. Historically,
      healthcare services have based coordination on skills standardization and, most
      recently, on processes standardization, through clinical guidelines, maps, and
      plans. Their utilisation is unsatisfactory in chronic diseases involving
      intervention by several professionals with reciprocal interdependencies,
      variability in patients' response to medical interventions, and a large volume of
      information to be processed. In this case, mechanisms based on feedback, such as
      working groups, linking professionals and vertical information systems, are more
      effective. To date, evaluation of healthcare coordination has not been conducted
      systematically, using structure, process and results indicators. The different
      strategies and instruments have been applied mainly to long-term care and mental
      health and one of the challenges to healthcare coordination is to extend and
      evaluate their use throughout the healthcare continuum.

PMID- 17198629
TI  - [Health sentinel networks in Spain. Consensus for a guide of principles and
      methods].
AB  - Since the eighties, health sentinel networks have been active in our country, but
      with a variety of objectives, methods and different development levels in the
      autonomous communities. The necessity of standardising the management and
      harmonising the indicators has concluded in a research project on the Spanish
      health sentinel networks, one of whose objectives is to establish a guide for
      work principles and methods. A panel of 23 experts has made a study using the
      Delphi method to agree, in three consecutive phases, a definition of sentinel
      network, the objectives and the management principles and other aspects related
      to the organisation and functioning. Altogether, 41 questions were gathered from
      a previous draft which needed 80% of consensus in the first phase and 70% in the
      second. All the experts participated in the first phase, 22 in the second and 20
      in the third. A consensus was achieved on 36 questions in the first phase and in
      4 of the remaining ones in the second. In the third phase the shape of the guide
      document was given. The Delphi consensus method has been extremely useful in the
      resolution of discrepancies and divergences. The experts who were selected
      outside of the sentinel networks contributed with a wider vision on the
      objectives and applicability of the health sentinel networks in Spain.

PMID- 17198630
TI  - [About the transfer of Western experiences to the Eastern Europe. Some avoidable
      errors when advising on health-care reforms].

PMID- 17198631
TI  - [Injuries from domestic violence in the Autonomous Community of Valencia
      (Spain)].
AB  - The lack of homogeneous and reliable epidemiological data on domestic violence
      greatly limits public decision making on the help that should be provided to
      victims of this form of abuse. Health professionals are obliged to report cases
      of domestic violence in adults to the judicial authorities and a unified, easily
      completed model for reporting injuries from domestic violence has been
      established in the Autonomous Community of Valencia. From June to October 2005,
      500 cases of domestic violence were received and processed, most of which were
      reported by primary care physicians (68%). Cases of domestic violence occurred
      mainly in young women (aged, 20-39 years), either married or cohabiting, and with
      primary or secondary level education. The most frequent findings were physical
      injury or psychological damage (62%). Eighty-three percent of victims had at
      least one antecedent of abuse.

PMID- 17198632
TI  - [Recovering birth rate, immigration and health in Catalonia].

PMID- 17198633
TI  - [Alcoholism in bus drivers].

PMID- 17198634
TI  - [The symbolism of containers].

PMID- 17198635
TI  - [Physicians faced with living liver donation: an attitudinal study in a Spanish
      hospital with a living donor liver transplant program].
AB  - INTRODUCTION: Mortality on the waiting list for liver transplants is high.
      Consequently, alternatives such as living donation are being sought. Therefore,
      one of the aspects that should be improved is the attitude of healthcare
      professionals toward this type of donation in order to create a favorable
      climate. The objective of this study was to identify attitudes toward living
      liver donation among physicians in a hospital with a living donor liver
      transplant program and to analyze the variables that affect these attitudes.
      PATIENTS AND METHODS: A random sample stratified by type of service (n = 369) was
      performed among physicians in the hospital. Attitudes were evaluated using a
      survey validated in our geographical area. In each service, the head of service,
      or in their absence, an attending physician, was contacted. This person was given
      an explanation of the study and was made responsible for distributing the
      questionnaire in selected work shifts. The questionnaire was completed
      anonymously and was self-administered. Statistical analysis consisted of chi2
      test, Student's t-test, and a logistic regression analysis. RESULTS: The survey
      completion rate was 93% (n = 345). Of those surveyed, 15% (n = 52) were in favor
      of living liver donation whether related or unrelated. This percentage increased
      to 85% (n = 292) if donation was related. Of the remainder, 8% (n = 27) did not
      accept living liver donation and the remaining 7% (n = 26) were undecided. This
      attitude was associated with only two factors: the respondent's belief that he or
      she might need a transplant in the future (p = 0.003) -90% of those who believed
      that they might need a transplant at some point in the future were in favor-, and
      the respondent's acceptance (if transplantation were necessary at some point in
      the future) of a living donated liver from a family member or a friend (p =
      0.000). Thus, 96% of those who would be prepared to accept a living organ were in
      favor. In the multivariate analysis, both variables remained significant: the
      respondent's belief that he or she might need a transplant in the future (odds
      ratio [OR] = 2.36) and, if this were the case, the respondent's acceptance of a
      living donated liver (OR = 7.11). CONCLUSIONS: Attitudes toward living liver
      donation among physicians in a hospital with a living donor transplant program
      were highly favorable. Consequently, these health professionals may be a key
      element for the promotion of living donation at the present time when this form
      of donation is being encouraged to avoid mortality on waiting lists.

PMID- 17198636
TI  - Risk for high-grade dysplasia or invasive carcinoma in colorectal flat adenomas
      in a Spanish population.
AB  - AIM: to determine the frequency and malignancy risk of colonic flat adenomas
      among patients with colorectal polyps in a Spanish population. METHODS: 1300
      consecutive colonoscopic examinations were reviewed; 640 polyps were detected and
      removed endoscopically in 298 patients. Chromoendoscopy with 0.2% indigo carmine
      was applied to clarify the macroscopical appearance of flat lesions. The
      following data was collected for flat and protruding polyps: size, location
      (proximal or distal to splenic flexure), histology (neoplastic or non
      neoplastic), high grade dysplasia (HGD) and submucosal invasive carcinoma (SIC)
      or beyond. RESULTS: 490 polyps (76.6%) were adenomas and 150 (23.4%)
      hyperplastic; 114 (23.3%) adenomas were flat (3 flat-depressed) whereas 376
      (76.7%) were protruding. The diameter of flat and protruding adenomas was 9.2 +/-
      7.9. mm and 7.0 +/- 5.9 mm, respectively (p < 0.001). A proximal location was
      more frequent for flat (63.1%) than for protruding adenomas (48.7%) (p = 0.003).
      The rate of HGD or SIC was significantly higher in flat than in protruding
      adenomas (7.0 vs 2.6%; p < 0.04). Two of the 3 flat-depressed lesions (both <or=
      10 mm in diameter) were carcinomas (T1 and T2, respectively). Flat adenomas had
      an increased risk for HGD or SIC (OR = 2,7; CI, 1,04-7,04; p < 0.05).
      CONCLUSIONS: In a Spanish population, flat adenomas represent nearly one quarter
      of all colorectal neoplastic polyps, their most frequent location being the right
      colon and they bear a higher risk of malignancy than protruding adenomas,
      especially for the flat depressed type.

PMID- 17198637
TI  - [Endoscopic insertion of self-expanding metal stents in malignant colonic
      obstructions].
AB  - BACKGROUND AND OBJECTIVE: Self-expanding metal stents are being increasingly used
      to resolve malignant colonic obstruction. Subsequently, patients can either
      undergo elective surgery, or the stent can serve as a definitive palliative
      treatment in patients unfit for surgery. We present our experience with this
      technique in our hospital, a level II center within the Spanish National Health
      Service, which can be considered a community hospital. PATIENTS AND METHODS: A
      retrospective study was performed of a 42-month period (May 2002 to October
      2005), during which malignant colonic obstruction was treated by means of
      endoscopically inserted stents on 43 occasions in 40 patients. RESULTS: Stent
      insertion was successfully performed in 41 attempts (95%) and good clinical
      results were obtained on 37 occasions (86%). Endoscopic means alone were used on
      23 occasions (53.5%) and in the remaining 20 (46.5%), both endoscopy and
      fluoroscopy were employed. Of 38 patients with successfully inserted stents,
      clinical success was achieved, as a whole, in 34. Twenty-four of these patients
      (63%) subsequently underwent elective surgery while the stent served as a
      definitive palliative treatment in the remaining 14 (37%). One of these patients
      had to undergo further surgery due to a fistula between the colon and the
      bladder. There were eight other complications: three stent migrations and one
      stent obstruction occurred, two patients had tenesmus, one patient developed
      bacteremia after stent insertion, and a silent bowel perforation by the stent was
      found in an elective surgical procedure. There was no mortality. CONCLUSIONS: In
      our experience, endoscopically inserted stents seem to be a safe and effective
      method for the initial treatment of malignant colonic obstruction.

PMID- 17198638
TI  - [Pulmonary toxicity associated with sirolimus therapy in liver transplantation].
AB  - Sirolimus is a potent immunosuppressive drug that began to be used in the last
      few years. This drug was initially used in renal transplantation but its use in
      other solid organ transplantations such as liver, heart, lung and pancreas, has
      been increasing. Sirolimus is indicated in rescue therapies and to reduce the
      secondary toxic effects of calcineurin inhibitors. However, this drug has been
      associated with infrequent but severe pulmonary toxicity and cases of
      interstitial pneumonitis, bronchiolitis obliterans with organizing pneumonia, and
      alveolar proteinosis have been described. We present the case of a male liver
      transplant recipient who developed interstitial pneumonitis associated with
      sirolimus use.

PMID- 17198639
TI  - [Cronkhite-Canada syndrome: an acquired, potentially reversible polyposis].
AB  - Cronkhite-Canada syndrome is an infrequent, nonadenomatous, acquired polyposis
      that is associated with ectodermic alterations. The etiopathogenesis and optimal
      therapeutic management are unknown. We present a case of Cronkhite-Canada
      syndrome in a 58-year-old man who, after combined treatment with corticosteroids,
      disodium cromoglycate, loratadine, ciprofloxacin, and zinc, showed complete
      clinical and partial endoscopic remission. The polypoid lesions of Cronkhite
      Canada syndrome can be reversed with medical treatment. Consequently, the natural
      history of the disease can be modified and its prognosis improved.

PMID- 17198640
TI  - [Intermediate-risk gastrointestinal stromal tumor: diagnosis through hydrogastric
      ultrasonography].
AB  - Evaluation of submucosal lesions of the digestive tract with conventional
      endoscopy is unsatisfactory since this technique does not allow direct
      observation or correct evaluation of the size and layer of origin of the tumor;
      therefore, in most patients an etiological diagnosis cannot be established with
      this procedure. However, in most patients, endoscopic ultrasonography can resolve
      these problems: to a fair degree of certainty, this technique can differentiate
      malignant from benign lesions, measure their size, and establish their layer of
      origin. Endoscopic ultrasonography is the technique of choice to establish the
      presence and characteristics of submucosal tumors and their suitability for
      treatment. Moreover, this procedure can identify tumors that can be removed
      endoscopically without excessive risk. Hydrogastric ultrasonography can be an
      effective substitute for echoendoscopy when evaluating submucosal lesions and for
      staging tumors of the gastric antrum when echoendoscopy is not available or in
      patients in whom it cannot be performed. Hydrogastric ultrasonography is safe,
      inexpensive and very well tolerated by patients. We present the case of a female
      patient with a gastric GIST that was evaluated using hydrogastric
      ultrasonography. The size, layer of origin, and malignancy of the tumor were
      accurately established.

PMID- 17198641
TI  - [Familial adenomatous polyposis].
AB  - Familial adenomatous polyposis is a rare genetic disease characterized by the
      development of more than a hundred adenomatous polyps in the colorectal area, as
      well as by extracolonic manifestations. Without treatment, this inherited
      disease, usually transmitted by autosomal dominant inheritance, predisposes to
      colorectal cancer. Treatment must be preceded by counseling about the nature of
      the syndrome and by recommendations for the optimal management and surveillance
      of the disease. Currently, prophylactic surgical therapy is imperative. However,
      the type of surgical technique used depends mainly on the severity of the
      polyposis phenotype, the age of the patient at diagnosis, and a series of special
      clinical circumstances. Lifetime follow-up of all patients is required. This
      article reviews the main studies published on familial adenomatous polyposis in
      order to provide an update on the most appropriate management of these patients.

PMID- 17198642
TI  - [Diagnostic approach to ischemic colitis].
AB  - Ischemic colitis is the most frequent form of intestinal ischemia and arises when
      the colon is temporarily deprived of blood supply. Diagnosis of this entity
      requires a high index of clinical suspicion. To achieve this, the chronology of
      the symptoms (abdominal pain followed by defecatory urgency and rectorrhagia) and
      the clinical context in which these symptoms appear (> 90% affect persons
      especially at risk for vascular accidents) must be taken into account. Although
      diagnosis requires early colonoscopy (< 48 h), this procedure should not be
      performed if peritonitis is present. In severe forms, other imaging techniques,
      such as Doppler ultrasound or abdominal computed tomography, provide information
      with diagnostic -and even prognostic- value. Angiography is reserved for patients
      in whom there is doubt about the presence of acute mesenteric ischemia.
      Thrombophilia should be investigated in persons aged less than 60 years old.

PMID- 17198643
TI  - [Covered transjugular intrahepatic portosystemic shunts].
AB  - Transjugular intrahepatic portosystemic shunts (TIPS) consist of a connection
      created by methods of interventionist radiology between the vena porta and the
      vena cava through the hepatic parenchyma. By markedly decreasing the portal
      pressure gradient, TIPS are highly effective in controlling the complications of
      portal hypertension such as bleeding due to esophageal varices and refractory
      ascites. Nevertheless, with the use of uncovered stents, the probability of shunt
      dysfunction -with the consequent reappearance of portal hypertension and its
      complications- is very high. The use of expandable polytetrafluoroethylene (e
      PTFE)-covered stents markedly reduces the incidence of dysfunction, thus
      decreasing the number of clinical recurrences of portal hypertension and the
      reinterventions required to maintain shunt patency. The greater effectiveness of
      e-PTFE-covered stents is not accompanied by a higher incidence of complications
      or hepatic encephalopathy. Therefore, e-PTFE-covered stents should be preferred
      over uncovered stents in the management of the complications of portal
      hypertension.

PMID- 17198644
TI  - [Acute pancreatitis as a presentation of panarteritis nodosa associated with
      hepatitis C: tuberculous reactivation due to triple immunosuppressive therapy].

PMID- 17198645
TI  - [Cholestatic hepatitis as the first manifestation of secondary syphilis].

PMID- 17198646
TI  - [Initial diagnosis of leishmaniasis in endoscopic gastrointestinal biopsy. Report
      of 2 cases].

PMID- 17198647
TI  - [Chronotherapy with torasemide in hypertensive patients: increased efficacy and
      therapeutic coverage with bedtime administration].
AB  - BACKGROUND AND OBJECTIVE: Torasemide is a high ceiling loop diuretic frequently
      used for treatment of heart failure, renal failure and hypertension, according to
      results mainly based on clinic blood pressure measurements, without proper
      evaluation of the 24-hour efficacy of the drug. Accordingly, we investigated the
      time-dependent antihypertensive efficacy of torasemide in hypertensive patients.
      PATIENTS AND METHOD: We studied 58 patients with grade 1-2 essential hypertension
      (25 men and 33 women), 48.7 (11.9) years of age, randomly assigned to receive
      torasemide (5 mg/day) either upon awakening or at bedtime. Blood pressure was
      measured by ambulatory monitoring for 48 consecutive hours before and after 6
      weeks of therapy. RESULTS: Efficacy of torasemide was significantly higher with
      bedtime dosing (11.2 and 8.0 mmHg reduction in the 24-hour mean of systolic and
      diastolic blood pressure, respectively) as compared to the administration of the
      drug on awakening (6.2 and 3.7 mmHg reduction in systolic and diastolic blood
      pressure). The percentage of patients with controlled ambulatory blood pressure
      after treatment was also higher after bedtime treatment (54% versus 27%). The
      time-response curves indicate a full 24-hour therapeutic duration only when
      torasemide was administered before bedtime. With regard to the safety profile, 2
      patients presented secondary effects (abdominal pain, diarrhea) in morning dose,
      and 4 patients taking the drug at bedtime reported nicturia. CONCLUSIONS: A dose
      of 5 mg/day torasemide is effective for blood pressure reduction after bedtime
      administration. The differences in efficacy and therapeutic duration as a
      function of the circadian time of treatment with torasemide here documented
      should be taken into account when prescribing this loop diuretic for treatment of
      patients with essential hypertension.

PMID- 17198648
TI  - [Urinary iodide assessment of the adult population in Catalonia].
AB  - BACKGROUND AND OBJECTIVE: In 1983 goitre prevalence in Catalonia (Spain) was 21%
      and average urinary iodine (UI) 88.5 microg/l (SD 47.5). Surveys carried out in
      the nineties, after a campaign promoting the use of iodized salt, showed a
      significant improvement in UI. In the framework of Catalan Health Examination
      (2002), the assessment of iodine deficiency was included. The aim of this study
      was to determine UI and its distribution among a representative sample of
      population aged 18-74 in Catalonia. SUBJECTS AND METHOD: A sample of 2,100 people
      were stratified in accordance with the eight Catalan health areas (CHA). A
      questionnaire was prepared and urinary samples were collected for iodine testing.
      RESULTS: 1,115 urinary samples were collected (in 7 of the 8 CHA). Median UI was
      147 microg/l and average UI 182.8 (SD 140). UI < 50 microg/l was found in 5% (95%
      CI, 3.8-6.5) of the sample. No difference in average UI was found between sexes.
      In fertile women (< 45 years) the 25th percentile of UI was 98 microg/l. Among
      CHA, average UI ranges from 141 to 159 microg/l. No difference in social class,
      education or employment was found in average UI. CONCLUSIONS: Our results show a
      significant improvement in iodine level of the Catalan population. Average UI is
      within the levels recommended by the WHO. However, it must be taken into account
      that 25% of fertile women have UI < 98 microg/l. This implies a risk in the event
      of pregnancy.

PMID- 17198650
TI  - [Effectivity of data obtention previous to drug commercialization: utopy or
      reality?].

PMID- 17198649
TI  - [Cross-cultural adaptation of the Eating Disorder Examination into Spanish].
AB  - BACKGROUND AND OBJECTIVE: This study presents a cross-cultural adaptation into
      Spanish of the Eating Disorder Examination (EDE) by Fairburn and Cooper (1993).
      MATERIAL AND METHOD: The original English version was adapted by means of a
      complex successive translation-backtranslation procedure. The final Spanish
      version was then applied to 50 patients with eating disorders (17 diagnosed for
      anorexia nervosa, 19 for bulimia nervosa, and 14 for binge eating disorder) and
      to 30 normal control subjects. RESULTS: The means and standard deviations of the
      group in the 4 subscales were similar to the data obtained by the normative
      studies of the original English version. The Spanish version also showed
      similarly high Cronbach alpha coefficients for reliability. As for discriminative
      validity, the subscales discriminated significantly between the clinical groups
      and the control group. CONCLUSIONS: The Spanish version of the EDE presents
      adequate psychometric properties, similar to the original version.

PMID- 17198651
TI  - [Surgical treatment for vascular necrosis of femoral head after hematopoietic
      stem cell transplantation].
AB  - BACKGROUND AND OBJECTIVE: Avascular necrosis of femoral head (AVN) has been
      identified as a frequent complication after hematopoietic stem cell
      transplantation (HSCT). Advances in the treatment for haematological malignancies
      have improved survival after HSCT. The aim of this study was to report the short
      and medium-term results of total hip arthroplasty for the treatment of AVN.
      PATIENTS AND METHOD: We performed 12 consecutive total hip arthroplasties (THA)
      with at least 2 year follow up. The diagnosis was AVN in the context of HSCT.
      Except for one, in all the patients THA was the first surgical procedure.
      RESULTS: On the Merle D'Augbigne and Postel grading system, 83% hips were good or
      excellent. There were no revisions for septic or aseptic loosening. CONCLUSIONS:
      We conclude that, in our experience, THA provided a good short and medium term
      follow up in patients with AVN after HSCT, and it seems to be a safe and
      effective treatment and the best option after conservative treatment failure.

PMID- 17198652
TI  - [Policies to reduce harm caused by alcohol use: a public health perspective].

PMID- 17198653
TI  - [Headache].

PMID- 17198654
TI  - [Anal intraepithelial neoplasia].
AB  - Human papillomavirus (HPV) is responsible for anal condylomata, anal
      intraepithelial neoplasia (AIN) and anal squamous cell carcinoma. AIN is a
      premalignant condition that can progress to invasive carcinoma through different
      grades of severity of the disease called AIN I, AIN II and AIN III. This paper
      looks at the current definition, diagnostic methods and management of AIN. The
      incidence of AIN has increased significantly in the last decades. The groups at
      risk are mainly patients with infection with human immunodeficiency virus,
      immunossuppressed patients and patients affected by HPV related diseases (e.g.,
      cervical cancer or anal condyloma). Accurate diagnosis of AIN lesions consists of
      accurate grading and disease extension. Low grade AIN (AIN I) or in extensive
      lesions, follow-up is advised to determine the possible evolution to anal
      squamous cell carcinoma. In cases of more severe and localized lesions (AIN II
      and AIN III), surgical resection should be considered if the predictive
      postoperative morbidity is low. Screening programs for AIN are not currently in
      place and there might be much effort to study the management of HPV in these
      patients.

PMID- 17198655
TI  - [Suppression of tobacco consumption during psychiatric hospitalization].

PMID- 17198656
TI  - [Clopidrogrel and deficiency of glucose 6 phosphate dehydrogenase].

PMID- 17198657
TI  - [The other face of forensic medicine].

PMID- 17198658
TI  - [Sneddon's syndrome and pyoderma gangrenosum].

PMID- 17198659
TI  - [Acute electrocardiographic pseudounfarction pattern and non-cardiogenic
      pulmonary edema in diabetic ketoacidosis].

PMID- 17198660
TI  - [Toxicity due to oleander (Nerium oleander) ingestion].

PMID- 17198661
TI  - [Microalbuminuria in diabetic and hypertensive patients: a study of 979
      patients].
AB  - BACKGROUND AND OBJECTIVE: Microalbuminuria is a known complication of diabetes
      mellitus but it is also a cardiovascular risk factor commonly present among
      hypertensive (non diabetic) population. The prevalence of microalbuminuria is
      variable and it has been never estimated in our region. The aim of this study has
      been to determine the prevalence of microalbuminuria in hypertensive (non
      diabetic) and diabetic population in Extremadura (Spain). PATIENTS AND METHOD:
      The study included diabetic patients and non-diabetic hypertensive ones randomly
      selected. Microalbuminuria was measured in every patient using albumin/creatinin
      reactive stick in fasting first morning urine. Whenever possible microalbuminuria
      was confirmed in laboratory by microalbuminuria/creatinina coefficient in first
      morning urine samples. RESULTS: A total of 979 patients (mean age [SD], 67.9
      [10.8] years; 409 men and 570 women, 505 diabetics) were studied. The presence of
      microalbuminuria was found in 12.4% of hypertensive patients and in 21.4% of
      diabetic patients (p < 0.001). Hypertensives and normotensive diabetics showed a
      similar prevalence of microalbuminuria (13.3%, not significant), but it tripled
      in hypertensive diabetics (33.8; p < 0.01). Glicemic control was not different
      for microalbuminuric diabetic patients and non microalbuminuric ones. The
      patients receiving rennin-angiotensin axis blocking drugs do not showed less
      prevalence of microalbuminuria (hypertensives 10.5%, diabetics 23.5%).
      Microalbuminuria was confirmed in 65.4% of patients. CONCLUSIONS: The prevalence
      of microalbuminuria in Extremadura seems to be high either in diabetics or non
      diabetic hypertensive patients. The finding of microalbuminuria in diabetics
      patients correlates with hypertension but do not with glicemic control. The
      prevalence of microalbuminuria is high in spite of using rennin-angiotensin axis
      blocking drugs.

PMID- 17198662
TI  - [Control of coronary risk factors in secondary prevention: PRESENAP study].
AB  - BACKGROUND AND OBJECTIVE: Evaluate the overall achievement of goals in the
      control of risk factors in secondary prevention in patients who have suffered a
      coronary event and are followed up in primary care centers. PATIENTS AND METHOD:
      Descriptive, transversal, multicenter study with sampling by consecutive
      inclusion of the first 5 patients attending the doctor's office who had suffered
      a coronary event 6 months to 10 years previously. The targets for control were:
      blood pressure < 140/90 mmHg in the general population and < 130/85 mmHg in
      diabetics; LDL-cholesterol < 100 mg/dl and no smoking habit. RESULTS: 8,817
      patients (73.7% males) were included, with a mean (SD) age of 65.4 (10.3) years;
      76.6% were hypertensive, 73.4% dyslipidemic and 32.7% diabetics; 60.2% achieved
      target blood pressure; 26.3% achieved LDL-cholesterol <100 mg/dl and 11.4%
      continued smoking; 16.4% fulfilled all recommendations. Factors independently
      related with good control were a lower age, male sex, patients who had been
      admitted with acute coronary syndrome without ST elevation (OR = 1.39; CI 95%,
      1.01-1.93; p = 0.04) or for revascularization (OR = 1.37; CI 95%; 1.12-1.67; p =
      0.002), patients with peripheral arterial disease (OR = 1.43; CI 95%, 1.11-1.84;
      p = 0.005) and when the physicians proposed suitable objectives (OR = 1.90; CI
      95%, 1.48-2.44; p < 0.0001). Control was poorer in hypertensive or dyslipidemic
      patients. CONCLUSIONS: Overall control of risk factors in secondary prevention of
      coronary disease is achieved in one in six patients attending primary care.

PMID- 17198663
TI  - [Antidotes availability in health services of Catalonia, Spain].
AB  - BACKGROUND AND OBJECTIVE: Acute poisoning can be treated in different hospital
      and extrahospital health services. Thus, availability of antidotes in hospital
      pharmacies, emergency departments and health centres play an important role in
      poisoning treatment. MATERIAL AND METHOD: This is a descriptive and transversal
      study of antidotes availability in different health services of Catalonia
      (Spain). From April to May 2005, a proper questionnaire was sent to 50 different
      health centres: 28 basic health centres (including medical ambulances) and 22
      hospitals with a distinct medical complexity level, to assess the qualitative
      (QLA) and quantitative availability (QTA) of antidotes. RESULTS: QLA resulted to
      be 82% in extrahospital health centres and 50% in medical ambulances. QTA was 94%
      for ambulances, whereas, in health centres, differences were observed between
      rural (55%) and urban (33%) areas. Regarding basic general hospitals (level 1),
      reference hospitals (level II) and high technology hospitals (level III) the QLA
      showed values of 39, 54 and 55%, respectively, and the QTA came about 70, 54 y
      54.5%, in that order. Furthermore, lack of adequate stocking was observed for
      compounded formulations, such as albumin, starch, ipecacuanha syrup or IV
      ethanol, and for essential antidotes as snake antivenin, digoxin immune Fab or
      hydroxocobalamine. CONCLUSIONS: There is understocking of poisoning antidotes
      throughout the health services of Catalonia. Heterogeneity was observed between
      services with a medical complexity level. The main deficiencies are found in
      antidotes that, to date, are available as compounded formulations or imported
      from other countries.

PMID- 17198664
TI  - [Overview of cardiovascular risk factors].

PMID- 17198665
TI  - [Cost of diabetes mellitus in Spain].

PMID- 17198666
TI  - [Disseminated intravascular coagulation].

PMID- 17198668
TI  - [Ferropenic anemia: some comments].

PMID- 17198669
TI  - [Megaloblastic anemia].

PMID- 17198667
TI  - [Safety of proton pump inhibitors].
AB  - The significant inhibitory capacity of gastric acid secretion of PPIs makes them
      the drugs of choice for treating acid-related diseases. The considerable
      prevalence of these diseases and the need for maintaining the administration of
      the drug during considerably long periods results in this therapeutic group being
      one of the most widely used. However, in spite of their extensive use, there
      continue to emerge concerns about their potential toxicity; concerns surrounding
      the specificity of their mechanism of action and a consequential suspicion that
      something so potent must involve harmful effects. PPIs act selectively on the
      final stage of the process of gastric acid secretion, namely the H+/K+-ATPase or
      proton pump. This enzyme represents an essential step in the process of secretion
      of H+, and PPIs exert a very specific action on the parietal cell, as they need
      an environment with very low pH levels, which only exist in this cell. In the
      present article, the adverse effects of PPIs are reviewed, with special emphasis
      on those related to their continued administration and on the special
      circumstances of patients, as in the case of the elderly, those with liver
      failure, pregnant and breastfeeding mothers and children. All the PPIs on the
      market share a common chemical basis and there are no great differences in their
      potential adverse effects, the possibility of them promoting opportunist
      infections or their capacity to generate pharmacokinetic interactions with other
      drugs, which, if occur, are generally insignificant. After two decades of use,
      PPIs have proved to be very effective and safe drugs.

PMID- 17198670
TI  - [Oral treatment of megaloblastic anemia with cobalamin].

PMID- 17198671
TI  - [Towards the best physician profile for the community].

PMID- 17198672
TI  - [About the best physician for the community].

PMID- 17198673
TI  - [Nosocomial infection surveillance in critically ill patients in the intensive
      care units].

PMID- 17198674
TI  - [Rhabdomyolisis and terbinafine].

PMID- 17198675
TI  - Spontaneous, intervesicular transfer rates of fluorescent, acyl chain-labeled
      phosphatidylcholine analogs.
AB  - It was recently shown that the structure of the fluorophore attached to the acyl
      chain of phosphatidylcholine analogs determines their mechanism of transport
      across the plasma membrane of yeast cells (Elvington et al., J. Biol Chem.
      280:40957, 2005). In order to gain further insight into the physical properties
      of these fluorescent phosphatidylcholine (PC) analogs, the rate and mechanism of
      their intervesicular transport was determined. The rate of spontaneous exchange
      was measured for PC analogs containing either NBD (7-nitrobenz-2-oxa-1,3-diazol-4
      yl), Bodipy FL (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene), Bodipy
      530 (4,4-difluoro-5,7-diphenyl-4-bora-3a,4a-diaza-s-indacene), or Bodipy 581 (4,4
      difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene) attached to a
      five or six carbon acyl chain in the sn-2 position. The rate of transfer between
      phospholipid vesicles was measured by monitoring the increase in fluorescence as
      the analogs transferred from donor vesicles containing self-quenching
      concentrations to unlabeled acceptor vesicles. Kinetic analysis indicated that
      the transfer of each analog occurred by diffusion through the water phase as
      opposed to transfer during vesicle collisions. The vesicle-to-monomer
      dissociation rate constants differed by over four orders of magnitude: NBD-PC
      (k(dis)=0.115 s(-1); t(1/2)=6.03 s); Bodipy FL-PC (k(dis)=5.2x10(-4); t(1/2)=22.2
      min); Bodipy 530-PC (k(dis)=1.52x10(-5); t(1/2)=12.6 h); and Bodipy 581-PC
      (k(dis)=5.9x10(-6); t(1/2)=32.6 h). The large differences in spontaneous rates of
      transfer through the water measured for these four fluorescent PC analogs reflect
      their hydrophobicity and may account for their recognition by different
      mechanisms of transport across the plasma membrane of yeast.

PMID- 17198676
TI  - Long-term regulation of cyclic nucleotide phosphodiesterase type 3B and 4 in 3T3
      L1 adipocytes.
AB  - Phosphodiesterase 3B (PDE3B), is known to play an important role in acute insulin
      and cAMP-mediated regulation of lipid metabolism, and PDE4 are the main PDE types
      expressed in adipocytes. Here, we show that members of all PDE4 isoforms are
      expressed in 3T3-L1 and primary mouse adipocytes. Long-term treatment of 3T3-L1
      adipocytes with insulin induced up-regulation of PDE3B and PDE4D in a
      phosphatidylinositol 3-kinase-dependent manner whereas long-term treatment with
      beta-adrenergic agonists induced down-regulation of PDE3B and up-regulation of
      PDE4D. Thus, PDE3B and PDE4D can be added to the list of genes regulated by
      insulin and cAMP-increasing hormones. Altered expression of PDE3B and PDE4D in
      response to long-term treatment with insulin and catecholamines may contribute to
      altered regulation of metabolism in diabetes.

PMID- 17198677
TI  - Dual inhibition of cyclooxygenase and lipoxygenase by human haptoglobin: its
      polymorphism and relation to hemoglobin binding.
AB  - Haptoglobin (Hp) binds hemoglobin (Hb) specifically and stoichiometrically. Since
      Hb stimulates prostaglandin (PG biosynthesis), we investigated if Hp effects
      arachidonic acid (AA) metabolism. The results showed that Hp (50-250 microg
      protein) inhibited the biosynthesis of PGs via cyclooxygenase (COX) and 12-HETE
      via lipoxygenase pathway in human platelets. Additional evidence was obtained by
      the loss of Hp inhibitory activity upon removal of Hp by affinity chromatography
      on hemoglobin sepharose and by inhibition of AA or bradykinin-induced
      bronchoconstriction in the guinea pig. Hb reduced the inhibitory effect of Hp in
      a concentration-related manner such that all its inhibitory activity was lost
      when completely bound by Hb. Of the three Hp phenotypes, Hp 1-1 showed maximum
      binding capacity to Hb indicating its greater protective role. These findings
      implicate Hp in the regulation of COX and lipoxygenase pathways and show Hp
      involvement in the body's endogenous defense system against inflammation. This
      indicates that mammals have dual defense system, i.e., a specific immune system
      and non-specific Hp defense system.

PMID- 17198678
TI  - Toxin binding to chimeric K+ channels immobilised on a solid nitrocellulose
      support.
AB  - In this work, we used a panel prokaryote/eukaryote K+ channel chimeras to
      generate K+ channel arrays. Their behaviour in solution was compared with that
      when spotted on a nitrocellulose-supported film and their responses to selective
      high affinity ligands, including polypeptide toxins and TEA, were studied.

PMID- 17198679
TI  - Neighboring-site effects of amino acid mutation.
AB  - Although the context dependence of nucleotide mutation has been supported by
      accumulating theoretical and experimental evidence, whether this effect can be
      extended to amino acid mutation remains obscure. As the amino acid doublets (20 x
      20) are much more diverse than their nucleotide counterparts (4 x 4), any attempt
      to address the neighboring-site effects of amino acid mutation was frustrated by
      deficient amino acid mutation data. Based on the recently revealed 599,745
      mutation sites in 45,137 orthologous proteins, we provide solid evidence for the
      first time to support the existence of neighboring-site effects in amino acid
      mutation, which is significantly important to improving the prevalent protein
      evolution models.

PMID- 17198681
TI  - The nuclear localization signal of mitotic kinesin-like protein Mklp-1: effect on
      Mklp-1 function during cytokinesis.
AB  - The mitotic kinesin-like protein (Mklp-1) localizes in the nucleus during
      interphase due to the presence of nuclear localization signal(s) [NLS(s)] within
      its sequence. Here, we mapped two NLSs to be 899SRKRRSST906 and 949KRKKP953 in
      the tail domain of Mklp-1, and showed that ectopic expression of a mutant Mklp-1
      without the NLSs leads to cell cycle arrest at cytokinesis, indicating that the
      NLSs are necessary for Mklp-1 to execute its normal function during cell
      division. Furthermore, mutation of two serine residues in the first NLS to
      aspartic acid, which mimics phosphorylation, attenuated its nuclear localization
      function, suggesting that the function of this NLS might be regulated by
      phosphorylation.

PMID- 17198680
TI  - Overproduction of collagen and diminished SOCS1 expression are causally linked in
      fibroblasts from idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal
      pulmonary disorder, and its pathology is characterized by parenchymal fibrosis.
      To investigate the characteristics of fibroblasts in IPF, we obtained eight
      fibroblast cell lines from lungs with IPF and eight lines from normal lungs. We
      found that the fibroblasts from IPF spontaneously produced higher amounts of type
      I collagen and had lower expression levels of SOCS1 than fibroblasts from normal
      lung. By using mouse fibroblasts, we demonstrated the causal relationship between
      them: the deficiency of SOCS1 in fibroblasts resulted in increased collagen
      production, whereas overexpression of SOCS1 suppressed collagen production. IFN
      gamma suppressed spontaneous collagen production even in SOCS1-deficient
      fibroblasts, indicating that IFN-gamma inhibition is SOCS1-independent. In
      contrast, IFN-gamma suppressed the increase of collagen production induced by IL
      4 in wild type fibroblasts but not SOCS1-deficient fibroblasts, suggesting IFN
      gamma acted exclusively via SOCS1 in this case. Following IFN-gamma stimulation,
      the amount of SOCS1 mRNA expressed by IPF fibroblasts was comparable to that of
      normal fibroblasts. Thus, the extent of SOCS1 increase after stimulation by IFN
      gamma was significantly higher in IPF fibroblasts. The extent to which IFN-gamma
      inhibited collagen production was also larger in IPF fibroblasts than in normal
      fibroblasts. These results suggest that the exaggerated production of collagen
      observed in fibroblasts from IPF is causally related to the diminished expression
      of SOCS1, and IPF fibroblasts are more susceptible to IFN-gamma because of
      decreased expression of SOCS1.

PMID- 17198682
TI  - Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL
      60 cells.
AB  - Curcumin has been shown to induce apoptosis in many cancer cells. However, the
      molecular mechanism(s) responsible for curcumin-induced apoptosis is not well
      understood and most probably involves several pathways. In HL-60 cells, curcumin
      induced apoptosis and endoplasmic reticulum (ER) stress as evidenced by the
      survival molecules such as phosphorylated protein kinase-like ER-resident kinase,
      phosphorylated eukaryotic initiation factor-2alpha, glucose-regulated protein-78,
      and the apoptotic molecules such as caspase-4 and CAAT/enhancer binding protein
      homologous protein (CHOP). Inhibition of caspase-4 activity by z-LEVD-FMK,
      blockage of CHOP expression by small interfering RNA, and treatment with
      salubrinal, an ER inhibitor, significantly reduced curcumin-induced apoptosis.
      Removing two double bonds in curcumin, which was speculated to form Michael
      adducts with thiols in secretory proteins, resulted in a loss of the ability of
      curcumin to induce apoptosis as well as ER stress. Thus, the present study shows
      that curcumin-induced apoptosis is associated with its ability to cause ER
      stress.

PMID- 17198683
TI  - The role of CpG methylation in cell type-specific expression of the aquaporin-5
      gene.
AB  - Aquaporin-5 (AQP5) is expressed in a cell type-specific manner. Here, we show
      that the AQP5 gene is regulated by CpG methylation. The AQP5 promoter containing
      a putative CpG island was highly methylated in NIH-3T3 or freshly isolated
      alveolar epithelial cells, correlating with the repression of this gene in these
      cells. In contrast, the AQP5 promoter was hypo-methylated in MLE-12 or cultured
      alveolar epithelial cells, which express high levels of AQP5. Repression of AQP5
      transcription in NIH-3T3 cells could be relieved with 5-azacytidine, and in vitro
      methylation of the AQP5 promoter resulted in inhibition of transcription of the
      reporter gene in MLE-12 cells. Chromatin immunoprecipitation assays showed that
      endogenous Sp1 bound to the hypo-methylated, but not highly methylated, AQP5
      promoter region. These results demonstrate that the hypo-methylated state of the
      AQP5 promoter leading to increased Sp1 binding may play a role in regulation of
      cell type-specific expression of the AQP5 gene.

PMID- 17198684
TI  - Characterization of a novel effect of hPinX1 on hTERT nucleolar localization.
AB  - The factor PinX1 has been shown as a telomerase inhibitor evolutionarily
      conserved in both the yeast and the human being. yPinX1 inhibits telomerase
      activity by sequestering yTERT (telomerase reverse transcriptase) from uniting
      with yTR (telomerase template RNA) in the nucleolus of yeast cells. However, the
      mechanism underlying the action of hPinX1 on telomerase regulation in human cells
      is not known. We here demonstrated that hPinX1 actually has an effect on
      mediating hTERT nucleolar localization and this effect is mediated by a novel
      domain enclosed within the central section of the polypeptide. Interestingly, we
      showed that a reported cancerous mutant form of hPinX1, in which residues of
      Ser254 and Cys265 are, respectively, mutated to Cys and Tyr, lost the activity on
      mediating hTERT nucleolar localization. Finally, we provided evidence that
      mediation of hTERT nucleolar localization and telomerase enzymatic inhibition are
      two separated function of hPinX1 on telomerase regulation in human cells.

PMID- 17198685
TI  - Effects of chronic unpredictable stress and methamphetamine on hippocampal
      glutamate function.
AB  - Although stress and methamphetamine (Meth) can independently and acutely affect
      glutamate transmission in the hippocampus, no studies have examined how chronic
      unpredictable stress modulates glutamate function and alters glutamate
      responsiveness to Meth. Therefore, the effects of chronic unpredictable stress on
      markers of glutamate function and subsequent Meth-induced increases in
      extracellular glutamate in the dorsal hippocampus were examined. Ten days of
      chronic unpredictable stress increased the plasmalemmal glial-glutamate
      transporter 2 (EAAT2) and increased vesicular glutamate transporter-1 (VGLUT1)
      immunoreactivity in a vesicle associated fraction. In addition, a 2-fold increase
      in vesicular glutamate content was observed. Chronic stress also enhanced Meth
      induced increases in extracellular glutamate in the dorsal hippocampus in a TTX
      dependent manner. Overall, the finding that chronic stress resulted in an
      upregulation of glutamate function and an enhanced glutamate response to Meth may
      have implications for glutamate responsiveness in chronically stressed animals
      exposed to other challenges or stressors.

PMID- 17198686
TI  - Cerebral blood flow and BOLD fMRI responses to hypoxia in awake and anesthetized
      rats.
AB  - This study investigated the functional MRI responses to graded hypoxia in
      awake/restrained and anesthetized animals by measuring cerebral blood flow (CBF)
      and blood oxygenation (BOLD) changes and estimating changes in cerebral metabolic
      rate of oxygen (CMRO2). Hypoxia in isoflurane anesthetized rats reduced blood
      pressure but did not change heart rate and respiration rate. In contrast, hypoxia
      in awake animals showed compensatory responses by sustaining blood pressure,
      increasing heart rate and respiration rate. Basal CBF was higher under isoflurane
      anesthesia than awake state because isoflurane is a vasodilator. Graded hypoxia
      decreased BOLD signals. Surprisingly, hypoxia also decreased CBF likely because
      hypoxia induced hypocapnia. Hypoxia-induced CBF and BOLD decreases were smaller
      in awake, relative to anesthetized, rats at low pO2, but similar at high pO2. CBF
      leveled off with decreasing hypoxia-induced pCO2 in awake rats, but monotonically
      decreased in anesthetized rats. CMRO2 estimated using a biophysical BOLD model
      did not change under mild hypoxia but was reduced under severe hypoxia relative
      to baseline. These results showed that isoflurane attenuated autonomic responses
      to hypoxia, hypoxia-induced hypocapnia dominated CBF changes, tissues in awake
      conditions appeared better oxygenated, and severe hypoxia reduced oxygen
      metabolism. This study underscored the marked differences in BOLD and CBF MRI
      responses to hypoxia in vivo between awake and anesthetized conditions and has
      implications for functional MRI studies of hypoxia in anesthetized animal models.

PMID- 17198688
TI  - Expression of steroid receptor coactivator-1 is elevated during neuronal
      differentiation of murine neural stem cells.
AB  - The cell-lineage-specific fate of neural stem cells (NSCs) is defined by spatial
      and temporal gene expression regulated by various transcription factors and their
      coregulators, including coactivators and corepressors. To clarify the cellular
      distribution of the steroid receptor coactivator-1 (SRC-1), a ligand-dependent
      nuclear receptor coactivator, during neurogenesis, we examined the expression
      profiles of SRC-1 during the proliferation and differentiation in culture of NSCs
      derived from the ganglionic eminence of mouse embryos. We found that SRC-1 was
      rarely expressed in proliferating cells and multipotent precursors with the
      typical characters of NSCs. Under conditions that promote the differentiation of
      NSCs, both the SRC-1 transcript and protein levels were elevated and the
      population of SRC-1-positive cells was found to be higher in the mature neurons
      than in the immature neurons. In contrast, SRC-1 expression was rarely localized
      in the glial lineage cells, including astrocytes and oligodendrocytes. These
      results indicate that SRC-1 expression accompanies the appearance of neuronal
      fate-committed cells derived from multipotent NSCs and is preferentially
      expressed in neuronal lineage cells during the differentiation of NSCs.

PMID- 17198687
TI  - ERP correlates of shared control mechanisms involved in saccade preparation and
      in covert attention.
AB  - We investigated whether attention shifts and eye movement preparation are
      mediated by shared control mechanisms, as claimed by the premotor theory of
      attention. ERPs were recorded in three tasks where directional cues presented at
      the beginning of each trial instructed participants to direct their attention to
      the cued side without eye movements (Covert task), to prepare an eye movement in
      the cued direction without attention shifts (Saccade task) or both (Combined
      task). A peripheral visual Go/Nogo stimulus that was presented 800 ms after cue
      onset signalled whether responses had to be executed or withheld. Lateralised ERP
      components triggered during the cue-target interval, which are assumed to reflect
      preparatory control mechanisms that mediate attentional orienting, were very
      similar across tasks. They were also present in the Saccade task, which was
      designed to discourage any concomitant covert attention shifts. These results
      support the hypothesis that saccade preparation and attentional orienting are
      implemented by common control structures. There were however systematic
      differences in the impact of eye movement programming and covert attention on
      ERPs triggered in response to visual stimuli at cued versus uncued locations. It
      is concluded that, although the preparatory processes underlying saccade
      programming and covert attentional orienting may be based on common mechanisms,
      they nevertheless differ in their spatially specific effects on visual
      information processing.

PMID- 17198689
TI  - Electrophysiological correlates of progressive sensorineural pathology in
      carboplatin-treated chinchillas.
AB  - Carboplatin produces progressive damage to auditory nerve fibers, spiral ganglion
      neurons (SGNs) and inner hair cells (IHC) in the chinchilla cochlea but leaves
      outer hair cells intact. Within 1 h after injection, many afferent terminals
      beneath IHCs and myelin lamellae surrounding SGN processes are vacuolated. One
      day after injection, approximately half of the nerve fibers are missing. IHCs are
      intact at 2 days, but 20-30% are missing at 3 days. We studied the
      electrophysiological correlates of this progressive morphological damage by
      recording cochlear microphonics (CM), distortion product otoacoustic emissions
      (DPOAE), summating potentials (SP), compound action potentials (CAP) and midbrain
      evoked potentials (IC-EVP) before and 1 h, 12 h, 1 days, 3 days, 5 days, 7 days
      and 14 days after carboplatin injection (75 mg/kg IP) in four chinchillas. CM and
      DPOAEs tended to be unchanged or enhanced. CAP and SP showed little change until
      Day 3, when amplitudes were reduced in all animals and CAP thresholds were
      elevated by 9 dB; amplitudes declined further between Days 3 and 5 but not
      thereafter. IC-EVP amplitudes decreased on Days 3 or 5 but thresholds were
      relatively unchanged. All animals showed some recovery of IC-EVP between Days 7
      and 14, including one with 70% enhancement on Day 14. The results indicate that
      threshold and amplitude measures fail to detect peripheral pathology until some
      relatively high threshold level of damage has been exceeded. This has important
      implications for monitoring peripheral damage and interpreting
      electrophysiological test results in animals and humans.

PMID- 17198691
TI  - Evidence for a role for the group I metabotropic glutamate receptor in the
      inhibitory effect of tumor necrosis factor-alpha on long-term potentiation.
AB  - Pro-inflammatory cytokines are known to be elevated in several neuropathological
      states that are associated with learning and memory. We have previously
      demonstrated in our laboratory that the inhibition of long-term potentiation
      (LTP) in the dentate gyrus region of the rat hippocampus, by tumor necrosis
      factor (TNF)-alpha, represents a biphasic response, an early phase dependent on
      p38 mitogen activated protein kinase (MAPK) activation and a later phase,
      possible dependent on protein synthesis. Many of the factors involved in the
      early modulation of LTP by TNF-alpha have yet to be elucidated. This study
      investigated if metabotropic glutamate receptors (mGluRs) are functionally linked
      to the inhibitory effect of TNF-alpha on LTP in the rat dentate gyrus in vitro.
      We report that the impairment of early-LTP by TNF-alpha is significantly
      attenuated by prior application of the group I/II mGluR antagonist MCPG and more
      specifically the mGluR5 antagonist MPEP. Since TNF-alpha is now known to cause
      transient increases in intracellular Ca(2+) levels from ryanodine-sensitive
      stores, we explored the possibility that disruption of intracellular Ca(2+)
      homeostasis could be involved. Ryanodine was found to significantly reverse the
      inhibition of LTP by TNF-alpha. From these studies we propose that the TNF-alpha
      inhibition of LTP is dependent upon the activation of TNFR1 and mGlu5-receptors.
      Importantly this study provides the first proof of the involvement of ryanodine
      sensitive intracellular Ca(2+) stores in TNF-alpha mediated inhibition of LTP.

PMID- 17198690
TI  - NMDA receptor 2B subunit-mediated synaptic transmission in the superficial dorsal
      horn of peripheral nerve-injured neuropathic mice.
AB  - Previous research has shown that peripheral inflammation and peripheral nerve
      injury alter the properties of NMDA receptors in the spinal dorsal horn. However,
      there is no direct evidence that demonstrates the influence of peripheral nerve
      injury on NMDA receptor-mediated synaptic transmission in the spinal dorsal horn.
      Using whole cell tight-seal methods, NMDA receptor-mediated excitatory
      postsynaptic currents (NMDA EPSCs) were recorded from superficial dorsal horn
      neurons in adult mouse spinal cord slices. Peripheral nerve injury-induced
      changes in the pharmacological and electrophysiological properties of synaptic
      NMDA receptors were studied. The ratio of the amplitude of NMDA EPSCs to that of
      non-NMDA EPSCs was larger in nerve-ligated neuropathic mice than in sham-operated
      control mice. The decay phase of the NMDA EPSCs was slower in nerve-ligated
      neuropathic mice. The NR2B subunit-specific NMDA receptor antagonist ifenprodil
      (10 microM) reduced the amplitude of the NMDA EPSCs and shortened their decay
      phase. The sensitivity of NMDA EPSCs to ifenprodil was significantly larger in
      nerve-ligated neuropathic mice than in sham-operated control mice. Single-cell RT
      PCR analysis performed on superficial dorsal horn neurons showed that the
      incidence of NR2A mRNA-expressing neurons was reduced in nerve-ligated
      neuropathic mice. This result, together with the electrophysiological findings,
      suggests that the subunit composition of the subsynaptic NMDA receptors in the
      superficial dorsal horn was altered by peripheral nerve injury. Pharmacological
      and electrophysiological changes observed in the present experiments might be the
      underlying causes of the hyperalgesia and allodynia induced by peripheral nerve
      injury and inflammation.

PMID- 17198692
TI  - Electrically evoked GABA release in rat hippocampus CA1 region and its changes
      during kindling epileptogenesis.
AB  - Previous findings on changes in K+-induced GABA release from hippocampal slices
      during kindling epileptogenesis were reinvestigated using physiological
      electrical stimulation. For that purpose, a procedure was developed enabling
      neurochemical monitoring of GABA release locally in the CA1 region of rat
      hippocampal slices upon tetanic stimulation of Schaffer-collateral fibers. In the
      presence of a GABA reuptake blocker, subsequent application of short (3 s) pulses
      of 50-Hz stimuli induced a local transient increase in GABA release. In slices
      from fully kindled animals, 24 h after the last generalized seizure, tetanically
      stimulated GABA release was increased in comparison to control slices. In slices
      from long-term kindled animals, 4-5 weeks after the last seizure, tetanically
      stimulated GABA release had returned to control levels. Application of the broad
      low-affinity GABAB receptor antagonist saclofen increased the tetanically
      stimulated GABA release in control slices, but had no effect in fully kindled
      slices. In slices from long-term kindled animals, however, saclofen enhanced GABA
      release similarly as in control slices. We conclude that the transient increase
      in tetanus-induced GABA release during kindling epileptogenesis is seizure
      related, and probably caused by temporarily impaired presynaptic GABAB receptors.
      The possible relevance of this finding for GABA transmission in epilepsy is
      discussed.

PMID- 17198694
TI  - Brain function during multi-trial learning in mild cognitive impairment: a PET
      activation study.
AB  - We explored functional brain changes with positron emission tomography (PET) in
      mild cognitive impairment (MCI) patients and elderly normal controls by employing
      an episodic memory task that included two successive encoding trials of
      semantically related word-pairs and final retrieval. Both groups demonstrated
      significant learning across the two trials. The control group showed
      predominantly left frontal activity during encoding, and right frontal plus left
      temporal activity during retrieval. However, the MCI patients recruited partly
      different brain regions. They failed to activate right frontal and left temporal
      areas during retrieval, and failed to show any different activation for encoding
      on the first and second trials, whereas the controls activated a region of
      posterior cingulate. There was indication of compensatory increases in rCBF of
      the occipital cortex during incremental learning and the left frontal lobe during
      retrieval in the patients. These results suggest different episodic memory
      processing in the MCI group, and a possible over-reliance on semantic processing.
      Subtle functional changes occur in the pre-Alzheimer brain before there are
      marked structural or behavioural abnormalities.

PMID- 17198695
TI  - Assessment of physical fitness in adults by field testing supported by the
      specific software for personal computer based use.
AB  - Physical inactivity is the second most important risk factor for development of
      cardiovascular diseases. Various field tests were developed for assessment of the
      fitness in general population. We aimed to assess the applicability and
      effectiveness of the specific software for UKK 2-km walking test data management.
      Descriptive results and statistical analysis on physical fitness of 383 adults
      are presented. The UKK 2-km walking test could be used as a feasible alternative
      for measurement of cardiovascular fitness. The test was integrated to exercise
      related health promotion programme, and widely available information technologies
      will be used for data management.

PMID- 17198693
TI  - Chronic alcohol drinking alters neuronal dendritic spines in the brain reward
      center nucleus accumbens.
AB  - Alcohol is known to affect glutamate transmission. However, how chronic alcohol
      affects the synaptic structure mediating glutamate transmission is unknown.
      Repeated alcohol exposure in a subject with familial alcoholic history often
      leads to alcohol addiction. The current study adopts alcohol-preferring rats,
      which are known to develop high drinking. Two-photon microscopy analysis
      indicates that chronic alcohol of 14 weeks either, under continuous alcohol (C
      Alc) or with repeated deprivation (RD-Alc), causes dysmorphology--thickened,
      beaded, and disoriented dendrites that are reminiscent of reactive astrocytes--in
      a subpopulation of medium spiny neurons. The density of dendritic spines was
      found differentially lower in the nucleus accumbens of RD-Alc and C-Alc groups as
      compared with those of Water groups. Large-sized spines and multiple-headed
      spines were increased in the RD-Alc group. The NMDA receptor subunit NR1
      proteins, as analyzed with Western blot, were upregulated in C-Alc, but not in RD
      Alc. The upregulated NMDA receptor subunits of NR1 however, are predominantly a
      splice variant isoform with truncated exon 21, which is required for membrane
      bound trafficking or anchoring into a spine synaptic site. These maladaptations
      may contribute to the transformation of spines. The changes, in density and head
      size of spines and the corresponding NMDA receptors, demonstrated an alteration
      of microcircuitry for glutamate reception. The current study demonstrates for the
      first time that chronic alcohol exposure causes structural alteration of
      dendrites and their spines in the key reward brain region in animals that have a
      genetic background leading to alcohol addiction.

PMID- 17198696
TI  - SOCS3 is required to temporally fine-tune photoreceptor cell differentiation.
AB  - Suppressor of cytokine signaling 3 (SOCS3) is an intracellular, ligand-induced
      negative feedback modulator of STAT3 activation that acts during inflammation.
      Here, we demonstrate that SOCS3 expression is important for normal retinal
      development in the perinatal period. STAT3 is highly activated in the late
      embryonic retina, then downregulated at postnatal day 0 (P0), presumably by the
      depletion of upstream ligands. We found that SOCS3 was required after P0 to shut
      down the residual STAT3 activation; this loss of activated STAT3 leads to
      Rhodopsin expression and rod photoreceptor cell differentiation. SOCS3 deficiency
      failed to terminate STAT3 activation, thereby delaying expression of Rhodopsin
      and its upstream transcription factor, crx. Development subsequently continued,
      but its course was temporally erratic, probably because of faulty compensation.
      Interestingly, SOCS3 protein expression was first detected postnatally, after
      STAT3 activation was mostly downregulated. It initially appeared in some of the
      presumptive photoreceptor cells and gradually spread. SOCS3 mRNA level was
      constant from the late-embryonic to early-postnatal period. Post-transcriptional
      inhibition of SOCS3 protein expression maintains a high STAT3 activation during
      late embryogenesis, and after P0, releasing from the inhibition promptly
      terminates STAT3 activation. Thus, SOCS3 can act as a temporal fine-tuner of
      STAT3 activation during photoreceptor cell differentiation.

PMID- 17198697
TI  - Dosage-dependent transcriptional regulation by the calcineurin/NFAT signaling in
      developing myocardium transition.
AB  - Thin spongy myocardium is critical at early embryonic stage [before embryonic day
      (E) 13.5 in mice] to allow diffusion of oxygen and nutrients to the developing
      cardiomyocytes. However, establishment of compact myocardium at later stage (
      approximately E16.5) during development is necessary to prepare for the increase
      in demand for blood circulation. Elucidating molecular targets of the spongy
      compact myocardium transition between E13.5 and E16.5 in heart development is
      thus important. Previous studies demonstrated that multiple transcription factors
      and signaling pathways are involved in the regulation and function of the
      myocardium in heart development. Disruption of certain transcription factors or
      critical components of signaling pathways frequently causes structural
      malformation in heart and persistence of "thin spongy myocardium". We have
      recently demonstrated activation of the calcineurin/NFAT signaling pathway at
      E14.5 in developing myocardium. Constitutive inhibition of the calcineurin/NFAT
      signaling pathway caused embryonic lethality. Molecular targets downstream of the
      calcineurin/NFAT signaling pathway, however, remains elusive. Here, we report
      transcription targets, independently and dependently, regulated by the
      calcineurin/NFAT signaling during the E13.5-E16.5 myocardium transition. We have
      uncovered that expression of one-third of the induced genes during myocardium
      transition is calcineurin/NFAT-dependent. Among these calcineurin/NFAT-dependent
      transcription targets, there is a dosage-dependent regulation. Molecular studies
      indicate that formation of distinct NFAT:DNA complex, in part, accounts for the
      dosage-dependent regulation. Thus, in addition to temporal and spatial
      regulation, dosage-dependent threshold requirement provides another mechanism to
      modulate transcription response mediated by the calcineurin/NFAT signaling during
      heart development.

PMID- 17198698
TI  - Functional effects of the late sodium current inhibition by AZD7009 and lidocaine
      in rabbit isolated atrial and ventricular tissue and Purkinje fibre.
AB  - AZD7009 (tert-Butyl-2-(7-[(2S)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7
      diazabicyclo[3.3.1]non-3-yl)ethylcarbamate) is an antiarrhythmic agent that
      increases atrial refractoriness, shows high antiarrhythmic efficacy and has low
      proarrhythmic potential. This study was primarily undertaken to determine the
      effects of AZD7009 on the late sodium current and to examine the impact of late
      sodium current inhibition on action potential duration in various myocardial
      cells. AZD7009 inhibited the late sodium current in Chinese Hamster Ovary K1 (CHO
      K1) cells expressing hNa(v)1.5 with an IC(50) of 11+/-2 microM. The late sodium
      current in isolated rabbit atrial and ventricular myocytes was also concentration
      dependently inhibited by AZD7009. Action potentials were recorded during exposure
      to 5 microM E-4031 (1-[2-(6-methyl-2pyridyl)ethyl]-4-(4-methylsulfonyl
      aminobenzoyl)piperidine), a compound that selectively inhibits the rapid delayed
      rectifier potassium current (I(Kr)), and to E-4031 in combination with AZD7009 or
      lidocaine in rabbit atrial and ventricular tissue and Purkinje fibres. In
      Purkinje fibres, but not in ventricular tissue, AZD7009 and lidocaine attenuated
      the E-4031-induced action potential duration prolongation. In atrial cells,
      AZD7009, but not lidocaine, further prolonged the E-4031-induced action potential
      duration. E-4031 induced early afterdepolarisations (EADs) in Purkinje fibres,
      EADs that were totally suppressed by AZD7009 or lidocaine. In conclusion,
      excessive action potential duration prolongation induced by E-4031 was attenuated
      by AZD7009 and lidocaine in rabbit Purkinje fibre, but not in atrial or
      ventricular tissue, most likely by inhibiting the late sodium current.
      Furthermore, the opposite effect by AZD7009 on action potential duration in
      atrial tissue suggests that AZD7009, in addition to inhibiting I(Kr), also
      inhibits other repolarising currents in the atria.

PMID- 17198699
TI  - Extracellular glutamate and GABA in the ventral tegmental area of alcohol
      preferring AA and alcohol-avoiding ANA rats treated repeatedly with morphine.
AB  - Glutamate and gamma-amino-butyric acid (GABA) have been implicated in neuronal
      plasticity related to behavioral sensitization. In the present study, we examined
      morphine-induced changes in the extracellular concentrations of glutamate and
      GABA in the ventral tegmental area in alcohol-preferring Alko Alcohol (AA) and
      alcohol-avoiding Alko Non-Alcohol (ANA) rats that have previously been shown to
      differ in morphine-induced sensitization. The rats were given escalating doses (5
      20 mg/kg) of morphine every other day for five days. This treatment produced
      behavioral sensitization to locomotor effects of morphine in AA, but not in ANA
      rats, when challenged with an additional injection of morphine (10 mg/kg) 10 days
      later. Morphine also increased the levels of glutamate in the ventral tegmental
      area only in AA rats, while no significant changes were found in the
      extracellular concentrations of GABA between the lines. Challenging the morphine
      treated AA rats with ethanol (1.5 g/kg) did not modify the levels of glutamate or
      GABA. No changes in the concentrations of glutamate or GABA were seen in saline
      treated AA and ANA rats after morphine challenge. These results render increased
      glutamate transmission in the ventral tegmental area a potential contributor to
      the higher susceptibility of AA rats to morphine-induced behavioral and
      neurochemical effects relative to ANA rats.

PMID- 17198700
TI  - Methylphenidate and atomoxetine increase histamine release in rat prefrontal
      cortex.
AB  - Using microdialysis in rat prefrontal cortex, we found that 1 mg/kg of the
      stimulant methylphenidate and the non-stimulant atomoxetine, two widely used
      treatments for Attention Deficit/Hyperactivity Disorder (ADHD), produce robust
      increases in the extracellular levels of histamine, which plays a key role in
      attention, learning and memory. While the clinical response to ADHD drugs is
      typically attributed to modulation of norepinephrine and dopamine, this finding
      suggests enhanced histamine release may contribute to their efficacy as ADHD
      treatments.

PMID- 17198701
TI  - Canonical Wnt signaling transiently stimulates proliferation and enhances
      neurogenesis in neonatal neural progenitor cultures.
AB  - Canonical Wnt signaling triggers the formation of heterodimeric transcription
      factor complexes consisting of beta-catenin and T cell factors, and thereby
      controls the execution of specific genetic programs. During the expansion and
      neurogenic phases of embryonic neural development canonical Wnt signaling
      initially controls proliferation of neural progenitor cells, and later neuronal
      differentiation. Whether Wnt growth factors affect neural progenitor cells
      postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling
      on neural progenitors isolated from cerebral cortices of newborn mice. Expression
      profiling of pathway components revealed that these cells are fully equipped to
      respond to Wnt signals. However, Wnt pathway activation affected only a subset of
      neonatal progenitors and elicited a limited increase in proliferation and
      neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway
      activation only transiently stimulated S-phase entry but did not support long
      term proliferation of progenitor cultures. The dampened nature of the Wnt
      response correlates with the predominant expression of inhibitory pathway
      components and the rapid actuation of negative feedback mechanisms.
      Interestingly, in differentiating cell cultures activation of canonical Wnt
      signaling reduced Hes1 and Hes5 expression suggesting that during postnatal
      neural development, Wnt/beta-catenin signaling enhances neurogenesis from
      progenitor cells by interfering with Notch pathway activity.

PMID- 17198702
TI  - RhoB and the mammalian Diaphanous-related formin mDia2 in endosome trafficking.
AB  - Rho GTPases and the dynamic assembly and disassembly of actin filaments have been
      shown to have critical roles in both the internalization and trafficking of
      growth factor receptors. While all three mammalian Diaphanous-related (mDia1/2/3)
      formin GTPase effector proteins have been localized on endosomes, a role for
      their actin nucleation, filament elongation, and/or bundling remains poorly
      understood in the context of intracellular trafficking. In a study of a
      functional relationship between RhoB, a GTPase known to associate with both early
      and late-endosomes, and the formin mDia2, we show that 1) RhoB and mDia2
      interact on endosomes; 2) GTPase activity-the ability to hydrolyze GTP to GDP-is
      required for the ability of RhoB to govern endosome dynamics; and 3) the actin
      dynamics controlled by RhoB and mDia2 is necessary for vesicle trafficking. These
      studies further suggest that Rho GTPases significantly influence the activity of
      mDia family formins in driving cellular membrane remodeling through the
      regulation of actin dynamics.

PMID- 17198703
TI  - Anatomical integration of newly generated dentate granule neurons following
      traumatic brain injury in adult rats and its association to cognitive recovery.
AB  - The hippocampus is particularly vulnerable to traumatic brain injury (TBI), the
      consequences of which are manifested as learning and memory deficits. Following
      injury, substantive spontaneous cognitive recovery occurs, suggesting that innate
      repair mechanisms exist in the brain. However, the underlying mechanism
      contributing to this is largely unknown. The existence of neural stem cells in
      the adult hippocampal dentate gyrus (DG) and their proliferative response
      following injury led us to speculate that neurogenesis may contribute to
      cognitive recovery following TBI. To test this, we first examined the time course
      of cognitive recovery following lateral fluid percussion injury in rats.
      Cognitive deficits were tested at 11-15, 26-30 or 56-60 days post-injury using
      Morris Water Maze. At 11-15 and 26-30 days post-injury, animals displayed
      significant cognitive deficits, which were no longer apparent at 56-60 days post
      TBI, suggesting an innate cognitive recovery at 56-60 days. We next examined the
      proliferative response, maturational fate and integration of newly generated
      cells in the DG following injury. Specifically, rats received BrdU at 2-5 days
      post-injury followed by Fluorogold (FG) injection into the CA3 region at 56 days
      post-TBI. We found the majority of BrdU+ cells which survived for 10 weeks became
      dentate granule neurons, as assessed by NeuN and calbindin labeling,
      approximately 30% being labeled with FG, demonstrating their integration into the
      hippocampus. Additionally, some BrdU+ cells were synaptophysin-positive,
      suggesting they received synaptic input. Collectively, our data demonstrate the
      extensive anatomical integration of new born dentate granule neurons at the time
      when innate cognitive recovery is observed.

PMID- 17198704
TI  - Transient ischemia increases neuronal nitric oxide synthase, argininosuccinate
      synthetase and argininosuccinate lyase co-expression in rat striatal neurons.
AB  - In neurodegenerative diseases, an increased number of neuronal nitric oxide
      synthase (nNOS)-positive neurons was reported, but nothing is known on which are
      the neurons induced to express nNOS. Argininosuccinate synthetase (ASS),
      argininosuccinate lyase (ASL) and nNOS act in the L-arginine-NO-L-citrulline
      cycle permitting a correct NO production. In the brain, nNOS-positive neurons co
      expressing ASS were known, while those co-expressing ASL were not demonstrated.
      We investigated by immunohistochemistry the presence of these types of neurons in
      the rat striatum to verify whether there was a correlation between their changes
      due to neurotoxic insults and animal survival. Transient ischemia, a
      neurodegenerative insult model, was induced in rat brain by 2 h of middle
      cerebral artery occlusion. The striatum, the core of ischemia, was examined at
      24, 72 and 144 h after reperfusion and compared with that of rats in normal
      condition. ASS, ASL and nNOS-positive neurons, some of the latter also expressing
      ASS and ASL, were present both in normal and ischemic conditions. At 24 h after
      reperfusion, the number of the nNOS-positive neurons and the percentage of those
      co-expressing ASS and ASL were significantly increased in the animals with a
      longer survival and at 144 h after ischemia there was an almost complete restore
      of the number and/or percentage of these neurons. We hypothesize that the neurons
      induced to express nNOS were the ASS- and ASL-positive ones and that the neurons
      co-expressing nNOS, ASS and ASL, since having the enzymes necessary to maintain a
      correct NO production, might protect from neurotoxic insults.

PMID- 17198705
TI  - Principal findings from a multicenter trial investigating the safety of
      follicular-fluid meiosis-activating sterol for in vitro maturation of human
      cumulus-enclosed oocytes.
AB  - OBJECTIVE: To evaluate the safety of applying follicular-fluid meiosis-activating
      sterol (FF-MAS) in vitro to immature human oocytes. DESIGN: Phase I bicenter,
      randomized, parallel-group, controlled, partially blinded trial. SETTING: Third
      level referral academic centers, including reproductive biology and genetics
      laboratories. PATIENTS: Endocrinologically normal women with a medical indication
      for IVF or intracytoplasmic sperm injection, or healthy volunteers.
      INTERVENTION(S): Subjects were randomized at a ratio 1 to 6 into either
      conventional GnRH-agonist and recombinant FSH stimulation (IVO) for oocyte
      retrieval, or minimally stimulated in vitro maturation (IVM) with the use of
      recombinant FSH. Retrieved immature oocyte cumulus complexes were cultured for 30
      or 36 hours in one of six IVM culture conditions containing FF-MAS (range, 0.1-20
      microM). Polar body-extruded oocytes from the IVO and IVM groups were processed
      for chromosomal analysis. MAIN OUTCOME MEASURE(S): The primary endpoint was the
      incidence of metaphase II stage oocytes with numeric chromosomal abnormalities,
      using full (spectral karyotyping) or partial (fluorescent in situ hybridization
      with seven probes) karyotyping or Giemsa count. A secondary objective was to
      document the frequency of metaphase II oocytes after IVM with FF-MAS supplements.
      RESULT(S): Oocyte cumulus complexes obtained from the IVO (mean, 8.9) and IVM
      (mean, 6.2) groups had equal maturation rates. Compared to IVO, exposure of
      germinal-vesicle oocytes for a maturation period of 30 hours did not increase
      aneuploidy. An exposure period of 36 hours doubled the aneuploidy rate, but this
      was significant only for the 20-muM dose of FF-MAS. CONCLUSION: Inclusion of 1-10
      microM FF-MAS in a 30-hour IVM protocol is safe.

PMID- 17198706
TI  - Stent expansion in curved vessel and their interactions: a finite element
      analysis.
AB  - Coronary restenosis after angioplasty has been reduced by stenting procedure, but
      in-stent restenosis (ISR) has not been eliminated yet, especially in tortuous
      vessels. In this paper, we proposed a finite element method (FEM) to study the
      expansion of a stent in a curved vessel (the CV model) and their interactions. A
      model of the same stent in a straight vessel (the SV model) was also studied and
      mechanical parameters of both models were researched and compared, including
      final lumen area, tissue prolapse between stent struts and stress distribution.
      Results show that in the CV model, the vessel was straightened by stenting and a
      hinge effect can be observed at extremes of the stent. The maximum tissue
      prolapse of the CV model was more severe (0.079 mm) than the SV model (0.048 mm);
      and the minimum lumen area of the CV was decreased (6.10 mm(2)), compared to that
      of the SV model (6.28 mm(2)). Tissue stresses of the highest level were
      concentrated in the inner curvature of the CV model. The simulations offered some
      explanations for the clinical results of ISR in curved vessels and gave design
      suggestions of the stent and balloon for tortuous vessels. This FEM provides a
      tool to study mechanisms of stents in curved vessels and can improve new stent
      designs especially for tortuous vessels.

PMID- 17198707
TI  - Elastic properties of biological membranes influenced by attached proteins.
AB  - Positively charged proteins can attach themselves to the negatively charged outer
      surface of biological cell membranes and liposomes. In this work, the influence
      of the intrinsic shape of the membrane-attached proteins on the elastic
      properties of the membrane is considered theoretically. It is shown that
      attachment of anisotropic proteins to the outer surface of biological membranes
      may induce tubulation of the membrane. The attachment of semi-flexible rod-like
      proteins increases the local bending constant, while the attachment of semi
      flexible plate-like anisotropic proteins may also reduce the local bending
      constant of the membrane. The role of the hydrophobic protrusion of the attached
      protein which is embedded in the outer membrane layer is also discussed.

PMID- 17198709
TI  - Immunocompetence of Galleria mellonella: sex- and stage-specific differences and
      the physiological cost of mounting an immune response during metamorphosis.
AB  - The antibacterial immune response of the wax moth, Galleria mellonella, was
      analysed by use of an inhibition zone plate assay. We demonstrated significant
      stage-specific differences as the immune response was most effective in the
      pupal, next the larval and then the adult stage. In addition, we demonstrated
      that an immune challenge at the onset of, or during metamorphosis does not
      increase nor decrease the strength of the antibacterial immune response in the
      subsequent developmental stage(s). These findings illustrate that induced
      immunity is not preserved during metamorphosis but also deny any cost to the
      immune system itself. However, an immune challenge does induce a significant
      shortening of the direct development time and affects the mass loss during
      metamorphosis in a sex-dependent manner: males emerged smaller whereas the mass
      of females was not significantly affected. These observations indicate that there
      are sex-specific costs to mounting an immune response during metamorphosis which
      affect physiological traits, implicating a trade-off between immunity and
      development.

PMID- 17198708
TI  - Direct measurement of intervertebral disc maximum shear strain in six degrees of
      freedom: motions that place disc tissue at risk of injury.
AB  - Human intervertebral disc specimens were tested to determine the regions of
      largest maximum shear strain (MSS) experienced by disc tissues in each of three
      principal displacements and three rotations, and to identify the physiological
      rotations and displacements that may place the disc at greatest risk for large
      tissue strains and injury. Tearing of disc annulus may be initiated by large
      interlamellar shear strains. Nine human lumbar discs were tagged with
      radiographic markers on the endplates, disc periphery and with a grid of wires in
      the mid-transverse plane and subjected to each of the six principal displacements
      and rotations. Stereo-radiographs were taken in each position and digitized for
      reconstruction of the three-dimensional position of each marker. Maximum tissue
      shear strains were calculated from relative marker displacements and normalized
      by the input displacement or rotation. Lateral shear, compression, and lateral
      bending were the motions that produced the mean (95% confidence interval) largest
      mean MSS of 9.6 (0.7)%/mm, 9.0 (0.5)%/mm, and 5.8 (1.6)%/ degrees , respectively,
      and which occurred in the posterior, posterolateral and lateral peripheral
      regions of the disc. After taking into account the reported maximum physiological
      range of motion for each degree of freedom, motions producing the highest
      physiological MSS were lateral bending (57.8 (16.2)%) and flexion (38.3 (3.3)%),
      followed by lateral shear (14.4 (1.1)%) and compression (12.6 (0.7)%).

PMID- 17198711
TI  - Crystal structure of alkaline phosphatase from the Antarctic bacterium TAB5.
AB  - Alkaline phosphatases (APs) are non-specific phosphohydrolases that are widely
      used in molecular biology and diagnostics. We describe the structure of the cold
      active alkaline phosphatase from the Antarctic bacterium TAB5 (TAP). The fold and
      the active site geometry are conserved with the other AP structures, where the
      monomer has a large central beta-sheet enclosed by alpha-helices. The dimer
      interface of TAP is relatively small, and only a single loop from each monomer
      replaces the typical crown domain. The structure also has typical cold-adapted
      features; lack of disulfide bridges, low number of salt-bridges, and a loose
      dimer interface that completely lacks charged interactions. The dimer interface
      is more hydrophobic than that of the Escherichia coli AP and the interactions
      have tendency to pair with backbone atoms, which we propose to result from the
      cold adaptation of TAP. The structure contains two additional magnesium ions
      outside of the active site, which we believe to be involved in substrate binding
      as well as contributing to the local stability. The M4 site stabilises an
      interaction that anchors the substrate-coordinating R148. The M5 metal-binding
      site is in a region that stabilises metal coordination in the active site. In
      other APs the M5 binding area is supported by extensive salt-bridge
      stabilisation, as well as positively charged patches around the active site. We
      propose that these charges, and the TAP M5 binding, influence the release of the
      product phosphate and thus might influence the rate-determining step of the
      enzyme.

PMID- 17198710
TI  - Importance of the 5 S rRNA-binding ribosomal proteins for cell viability and
      translation in Escherichia coli.
AB  - A specific complex of 5 S rRNA and several ribosomal proteins is an integral part
      of ribosomes in all living organisms. Here we studied the importance of
      Escherichia coli genes rplE, rplR and rplY, encoding 5 S rRNA-binding ribosomal
      proteins L5, L18 and L25, respectively, for cell growth, viability and
      translation. Using recombineering to create gene replacements in the E. coli
      chromosome, it was shown that rplE and rplR are essential for cell viability,
      whereas cells deleted for rplY are viable, but grow noticeably slower than the
      parental strain. The slow growth of these L25-defective cells can be stimulated
      by a plasmid expressing the rplY gene and also by a plasmid bearing the gene for
      homologous to L25 general stress protein CTC from Bacillus subtilis. The rplY
      mutant ribosomes are physically normal and contain all ribosomal proteins except
      L25. The ribosomes from L25-defective and parental cells translate in vitro at
      the same rate either poly(U) or natural mRNA. The difference observed was that
      the mutant ribosomes synthesized less natural polypeptide, compared to wild-type
      ribosomes both in vivo and in vitro. We speculate that the defect is at the
      ribosome recycling step.

PMID- 17198712
TI  - Polymerase eta is a short-lived, proteasomally degraded protein that is
      temporarily stabilized following UV irradiation in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae Rad30 is the homolog of human DNA polymerase eta whose
      inactivation leads to the cancer-prone syndrome xeroderma pigmentosum variant.
      Both human and yeast polymerase eta are responsible for error-free bypass of UV
      induced cis-syn pyrimidine dimers and several other DNA lesions. Here we show,
      using yeast strains expressing TAP-tagged Rad30, that the level of this protein
      is post-translationally regulated via ubiquitination and proteasome-mediated
      degradation. The half-life of Rad30 is 20 min and it increases due to proteasomal
      defects. Mutations inactivating components of the Skp1/cullin/ F-box (SCF)
      ubiquitin ligase complex: Skp1 and the F-box protein Ufo1 stabilize Rad30. Our
      results indicate also that ultraviolet irradiation causes transient stabilization
      of Rad30, which leads, in turn, to temporary accumulation of this polymerase in
      the cell. We conclude that proteolysis plays an important role in regulating the
      cellular abundance of Rad30. These results are the first indication of a role for
      controlled proteasomal degradation in modulating cellular level of translesion
      DNA polymerase in eukaryotes.

PMID- 17198714
TI  - Nonlinear time series analysis of food intake in the dab and the rainbow trout.
AB  - Evidence suggests that dab and rainbow trout are able to quickly adjust their
      food intake to an appropriate level when offered novel diets. In addition day-to
      day and meal-to-meal food intake varies greatly and meal timing is plastic. Why
      this is the case is not clear: Food intake in fish is influenced by many factors,
      however the hierarchy and mechanisms by which these interact is not yet fully
      understood. A model of food intake may be helpful to understand these phenomena;
      to determine model type it is necessary to understand the qualitative nature of
      food intake. Food intake can be regarded as an autoregressive (AR) time series,
      as the amount of food eaten at time t will be influenced by previous meals, and
      this allows food intake to be considered using time series analyses. Here, time
      series data were analysed using nonlinear techniques to obtain qualitative
      information from which evidence for the hierarchy of mechanisms controlling food
      intake may be drawn. Time series were obtained for a group of dab and individuals
      and a group of rainbow trout for analysis. Surrogate data sets were generated to
      test several null hypotheses describing linear processes and all proved
      significantly different to the real data, suggesting nonlinear dynamics.
      Examination of topography and recurrence diagrams suggested that all series were
      deterministic and non-stationary. The point correlation dimension (PD2i)
      suggested low-dimensional dynamics. Our findings suggest therefore that any model
      of appetite should create output that is deterministic, non-stationary, low
      dimensional and having nonlinear dynamics.

PMID- 17198715
TI  - Exposure to genotoxic agents, host factors, and lifestyle influence the number of
      centromeric signals in micronuclei: a pooled re-analysis.
AB  - We pooled data from three biomonitoring studies using the cytokinesis-block
      micronucleus assay in peripheral blood lymphocytes in combination with
      fluorescence in situ hybridization. Centromere-positive micronuclei (C+MN) were
      classified in two groups: those containing one centromere (C1+MN) and those with
      two or more (Cx+MN). The three studies evaluated untreated cancer patients,
      welders, and pathologists/anatomists exposed to formaldehyde. The total number of
      subjects included in the pooled re-analysis was 113. A higher frequency of C+MN
      was observed in cancer patients and exposed workers, who showed significant
      differences from controls in all studies. C1+MN were particularly increased in
      the group of pathologists/anatomists, who showed a 3.29 times higher frequency
      than controls (95% CI: 2.04-5.30). A borderline increase in Cx+MN was observed in
      welders when compared to the corresponding control group (FR: 1.31; 95% CI: 0.99
      1.74). An evident effect of gender was found, with significantly increased
      frequencies of all endpoints measuring aneuploidy in females (C+MN, C1+MN, and
      Cx+MN). Alcohol consumption had a significant effect on total MN frequency and
      particularly on C+MN and C1+MN. In conclusion, scoring the number of centromeric
      signals in the micronucleus assay provides additional information about the
      mechanism of action of various genotoxic agents, and the role of confounding
      factors may be more specifically accounted for. Indeed, C+MN could be efficiently
      used in biomonitoring studies as an independent biomarker of exposure and early
      biological effect. The use of centromeric signals allows the identification of
      two further endpoints, representing two alternative pathways of chromosome loss,
      i.e., impaired chromosome migration, leading to increased C1+MN frequency, and
      centrosome amplification, possibly leading to Cx+MN with two or more centromeric
      signals.

PMID- 17198713
TI  - Molecular dissection of o29 scaffolding protein function in an in vitro assembly
      system.
AB  - An in vitro assembly system was developed to study prolate capsid assembly of
      phage o29 biochemically, and to identify regions of scaffolding protein required
      for its functions. The crowding agent polyethylene glycol can induce
      bacteriophage o29 monomeric capsid protein and dimeric scaffolding protein to co
      assemble to form particles which have the same geometry as either prolate T=3 Q=5
      procapsids formed in vivo or previously observed isometric particles. The
      formation of particles is a scaffolding-dependent reaction. The balance between
      the fidelity and efficiency of assembly is controlled by the concentration of
      crowding agent and temperature. The assembly process is salt sensitive,
      suggesting that the interactions between the scaffolding and coat proteins are
      electrostatic. Three N-terminal o29 scaffolding protein deletion mutants, Delta 1
      9, Delta 1-15 and Delta 1-22, abolish the assembly activity. Circular dichroism
      spectra indicate that these N-terminal deletions are accompanied by a loss of
      helicity. The inability of these proteins to dimerize suggests that the N
      terminal region of the scaffolding protein contributes to the dimer interface and
      maintains the structural integrity of the dimeric protein. Two C-terminal
      scaffolding protein deletion mutants, Delta 79-97 and Delta 62-97, also fail to
      promote assembly. However, the secondary structure and the dimerization ability
      of these mutants are unchanged relative to wild-type, which suggests that the C
      terminus is the likely site of interaction with the capsid protein.

PMID- 17198716
TI  - Somatosensory function in boys with ADHD and tactile defensiveness.
AB  - In this study, we tested for deficits in somatosensory function in boys with
      Attention Deficit Hyperactivity Disorder (ADHD) and tactile defensiveness (TD).
      The subjects were 67 boys with ADHD, sub-typed as TD (ADHD+TD+) or non TD
      (ADHD+TD-), matched with 60 "typical" children in the control group. Sixty nine
      percent of the boys with ADHD were categorized as TD. The groups were compared on
      three measures: (a) performance scores on subtests of the Sensory Integration and
      Praxis Test, (b) measurements of the Somatosensory Evoked Potential (SEP) and (c)
      ratings of the children's affective responses during tactile stimulation. Both
      ADHD groups differed from the control group on most study measures. No
      significant differences were found between the two ADHD subgroups on threshold
      and perceptual tests scores, except for Finger Identification. However, the TD+
      group demonstrated significantly higher central SEP amplitudes than did the TD-
      group. Together, the results support claims that TD is related to central
      processing of somatosensory information, but not to anomalous tactile perception,
      with the exception of Finger Identification.

PMID- 17198717
TI  - Isolation of Lawsonia intracellularis specific single-chain Fv antibody fragments
      from phage display library.
AB  - Single-chain antibodies (scFv) exhibiting specific binding to Lawsonia
      intracellularis were isolated from a phagemid library expressing scFvs molecules
      on the surface of filamentous bacteriophages. For scFv selection whole bacterial
      cells were used and individual clones were tested in ELISA test. The total of
      seven unique clones with different fingerprint profiles was isolated. All clones
      were able to bind specifically in immunofluorescence assay. This is the first
      report of species specific recombinant antibodies against L. intracellularis.

PMID- 17198718
TI  - The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular
      uptake of phalloidin and microcystin into skate liver.
AB  - Organic anion transporting polypeptides (rodent Oatp; human OATP) mediate
      cellular uptake of numerous organic compounds including xenobiotic toxins into
      mammalian hepatocytes. In the little skate Leucoraja erinacea a liver-specific
      Oatp (Oatp1d1, also called sOatp) has been identified and suggested to represent
      an evolutionarily ancient precursor of the mammalian liver OATP1B1 (human),
      Oatp1b2 (rat), and OATP1B3 (human). The present study tested whether Oatp1d1
      shares functional transport activity of the xenobiotic oligopeptide toxins
      phalloidin and microcystin with the mammalian liver Oatps/OATPs. The phalloidin
      analogue [(3)H]-demethylphalloin was taken up into skate hepatocytes with high
      affinity (Km approximately 0.4 microM), and uptake could be inhibited by
      phalloidin and a variety of typical Oatp/OATP substrates such as
      bromosulfophthalein, bile salts, estrone-3-sulfate, cyclosporine A and high
      concentrations of microcystin-LR (Ki approximately 150 microM). When expressed in
      Xenopus laevis oocytes Oatp1d1 increased uptake of demethylphalloin (Km
      approximately 2.2 microM) and microcystin-LR (Km approximately 27 microM) 2- to 3
      fold over water-injected oocytes, whereas the alternative skate liver organic
      anion transporter, the dimeric Ostalpha/beta, exhibited no phalloidin and only
      minor microcystin-LR transport. Also, the closest mammalian Oatp1d1 orthologue,
      the human brain and testis OATP1C1, did not show any phalloidin transport
      activity. These results demonstrate that the evolutionarily ancient Oatp1d1 is
      able to mediate uptake of cyclic oligopeptide toxins into skate liver. The
      findings support the notion that Oatp1d1 is a precursor of the liver-specific
      mammalian Oatps/OATPs and that its transport properties are closely associated
      with certain forms of toxic liver injury such as for example protein phosphatase
      inhibition by the water-borne toxin microcystin.

PMID- 17198719
TI  - Toxicokinetic and toxicodynamic analyses of Androctonus australis hector venom in
      rats: optimization of antivenom therapy.
AB  - This paper reports the simultaneous determination of toxicokinetic and
      toxicodynamic properties of Androctonus australis hector venom, in the absence
      and presence of antivenom (F(ab')(2) and Fab), in envenomed rats. After
      subcutaneous injection of the venom, toxins showed a complete absorption phase
      from the site of injection associated with a distribution into a large
      extravascular compartment. The injection of Fab and F(ab')(2) induced the
      neutralization of venom antigens in the blood compartment, as well as the
      redistribution of venom components from the extravascular compartment to the
      blood compartment. Interestingly, F(ab')(2) and Fab showed distinct efficiencies
      depending on their route of injection. F(ab')(2) induced a faster venom
      neutralization and redistribution than Fab when injected intravenously. Fab was
      more effective than F(ab')(2) by the intramuscular route. The hemodynamic effects
      of Aah venom were further investigated. Changes in mean arterial pressure and
      heart rate were observed in parallel with an upper airway obstruction. Fab was
      more effective than F(ab')(2) for preventing early symptoms of envenomation,
      whatever their route of administration. Intraperitoneal injection of F(ab')(2)
      and Fab was similar for the prevention of the delayed symptoms, even after a late
      administration. Fab was more effective than F(ab')(2) in the inhibition of airway
      resistance, independent of the route and time of administration. These results
      show that the treatment for scorpion stings might be improved by the
      intravascular injection of a mixture of Fab and F(ab')(2). If antivenom cannot be
      administered intravenously, Fab might be an alternative as they are more
      effective than F(ab')(2) when injected intramuscularly.

PMID- 17198721
TI  - Sequence of mammalian fossils, including hominoid teeth, from the Bubing Basin
      caves, South China.
AB  - A Plio-Pleistocene to Holocene faunal sequence has been recovered from four
      carefully excavated caves in the Bubing Basin, adjacent to the larger Bose Basin
      of South China. The caves vary in elevation; we suggest that the higher caves
      were formed and filled with sediments prior to the lower caves. The highest
      deposits, which are from Mohui Cave, contain hominoid teeth and other fossilized
      remains of mammalian taxa most similar to late Pliocene and early Pleistocene
      faunas. Wuyun Cave ( approximately 50m lower in elevation than Mohui) contains a
      late middle Pleistocene fauna, which is supported by U-series age constraints
      from 350 to 200ka. Lower Pubu Cave ( approximately 23m below Wuyun) is assigned
      to the late Pleistocene, while the Cunkong Cave (the lowest, approximately 2m
      lower elevation than Lower Pubu) preserves a Holocene fauna. The four faunal
      assemblages indicate species-level changes in Ailuropoda, Stegodon, and Sus, the
      appearance of Elephas, the local disappearance of Stegodon, and the migration of
      Equus hemionus to South China. These initial results of our work call into
      question the continued value of the Stegodon/Ailuropoda Fauna, a category long
      used to characterize the Pleistocene faunas of South China. Excavation of karstic
      caves of varying elevation within the basins of South China holds promise for
      defining local sequences of mammalian fossils that can be used to investigate
      faunal variations related to climate change, biogeographic events, and
      evolutionary change over the past two million years. Stable isotopic analysis of
      a small sample of mammalian teeth from Bubing Basin caves is consistent with 100%
      C(3) vegetation in the Bubing/Bose region, with certain delta(13)C values
      consistent with a canopied woodland or forest. A preliminary assessment of the
      hominoid teeth indicates the presence of diverse molar and premolar morphologies
      including dental remains of Gigantopithecus blacki and a sample with similarities
      to the teeth reported from Longgupo.

PMID- 17198722
TI  - Dolichopithecus balcanicus sp. nov., a new Colobinae (Primates, Cercopithecidae)
      from the early Pliocene of southeastern Europe, with a discussion on the taxonomy
      of the genus.
AB  - We describe a new species of Dolichopithecus, D. balcanicus sp. nov., from the
      Pliocene (late Ruscinian) of the Balkans. Although known by mandibular remains
      only, it is readily distinguished from the common European species, D.
      ruscinensis, by its smaller size, much shallower mandibular corpus, and crowding
      of the premolars. Ukrainian finds of "Adelopithecus" can be accommodated within
      D. ruscinensis as a separate, smaller subspecies, D. ruscinensis hypsilophus, but
      the specimens reported from Asia are more distinct, and they probably represent a
      separate subgenus of Dolichopithecus, the valid name of which is D.
      (Parapresbytis) Kalmykov and Mashchenko.

PMID- 17198720
TI  - Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential
      for insect control.
AB  - Bacillus thuringiensis Crystal (Cry) and Cytolitic (Cyt) protein families are a
      diverse group of proteins with activity against insects of different orders-
      Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as
      nematodes. Their primary action is to lyse midgut epithelial cells by inserting
      into the target membrane and forming pores. Among this group of proteins, members
      of the 3-Domain Cry family are used worldwide for insect control, and their mode
      of action has been characterized in some detail. Phylogenetic analyses
      established that the diversity of the 3-Domain Cry family evolved by the
      independent evolution of the three domains and by swapping of domain III among
      toxins. Like other pore-forming toxins (PFT) that affect mammals, Cry toxins
      interact with specific receptors located on the host cell surface and are
      activated by host proteases following receptor binding resulting in the formation
      of a pre-pore oligomeric structure that is insertion competent. In contrast, Cyt
      toxins directly interact with membrane lipids and insert into the membrane.
      Recent evidence suggests that Cyt synergize or overcome resistance to
      mosquitocidal-Cry proteins by functioning as a Cry-membrane bound receptor. In
      this review we summarize recent findings on the mode of action of Cry and Cyt
      toxins, and compare them to the mode of action of other bacterial PFT. Also, we
      discuss their use in the control of agricultural insect pests and insect vectors
      of human diseases.

PMID- 17198724
TI  - Effect of underground urban structures on eutrophic coastal environment.
AB  - The NIES Integrated Catchment-based Eco-hydrology (NICE) model was expanded to
      include the density current and solute-transport process of groundwater in the
      Kanto Plain and to incorporate the effects of water table and tidal fluctuations
      around the eutrophic Tokyo Bay, Japan (NICE-SEA). The simulation reproduced
      excellently the observed values of river discharge and groundwater level in the
      catchment. The simulated groundwater level shows a minus value (below the sea
      level) around the Tokyo metropolitan area because of excessive withdrawal around
      the urban area in the past. The model shows that the underground urban
      structures, sewage pipes, seashore concrete dikes, and embankments have changed
      the hydrologic cycle in the catchment and the nutrient supply to Tokyo Bay. In
      particular, the groundwater flow is interrupted and the phase is delayed,
      resulting in an increase in the groundwater level, and a decrease of groundwater
      seepage into Tokyo Bay. Furthermore, we propose four types of political scenario
      for provisioning human ecosystem service (ES) sites to promote infiltration. The
      simulated result forecasts that the groundwater level increases predominantly at
      a maximum value exceeding 40 cm in a scenario for farmland and productive green
      areas and that the level recovers in some parts of the urban area. This
      phenomenon is related to the cut-off of groundwater flow by underground urban
      structures and the sewer leakage into the aquifer, which also influences the
      decrease of submarine groundwater discharge around the western side of Tokyo Bay.

PMID- 17198723
TI  - Fish consumption and bioindicators of inorganic mercury exposure.
AB  - BACKGROUND: The direct and close relationship between fish consumption and blood
      and hair mercury (Hg) levels is well known, but the influence of fish consumption
      on inorganic mercury in blood (B-IHg) and in urine (U-Hg) is unclear. OBJECTIVE:
      Examine the relationship between fish consumption, total, inorganic and organic
      blood Hg levels and urinary Hg concentration. METHODS: A cross-sectional study
      was carried out on 171 persons from 7 riparian communities on the Tapajos River
      (Brazilian Amazon), with no history of inorganic Hg exposure from occupation or
      dental amalgams. During the rising water season in 2004, participants responded
      to a dietary survey, based on a seven-day recall of fish and fruit consumption
      frequency, and socio-demographic information was recorded. Blood and urine
      samples were collected. Total, organic and inorganic Hg in blood as well as U-Hg
      were determined by Atomic Absorption Spectrometry. RESULTS: On average,
      participants consumed 7.4 fish meals/week and 8.8 fruits/week. Blood total Hg
      averaged 38.6+/-21.7 microg/L, and the average percentage of B-IHg was 13.8%.
      Average organic Hg (MeHg) was 33.6+/-19.4 microg/L, B-IHg was 5.0+/-2.6 microg/L,
      while average U-Hg was 7.5+/-6.9 microg/L, with 19.9% of participants presenting
      U-Hg levels above 10 microg/L. B-IHg was highly significantly related to the
      number of meals of carnivorous fish, but no relation was observed with non
      carnivorous fish; it was negatively related to fruit consumption, increased with
      age, was higher among those who were born in the Tapajos region, and varied with
      community. U-Hg was also significantly related to carnivorous but not non
      carnivorous fish consumption, showed a tendency towards a negative relation with
      fruit consumption, was higher among men compared to women and higher among those
      born in the region. U-Hg was strongly related to I-Hg, blood methyl Hg (B-MeHg)
      and blood total Hg (B-THg). The Odds Ratio (OR) for U-Hg above 10 microg/L for
      those who ate >4 carnivorous fish meals/week was 4.00 [1.83-9.20]. CONCLUSION:
      This study adds further evidence to a positive relation between fish consumption
      and IHg in both blood and urine, which may result from absorption of IHg from
      fish or from demethylation of MeHg. The findings support the importance of
      assessing IHg exposure in fish-eating communities. Further studies should examine
      the potential toxicity of IHg in heavy fish consumers.

PMID- 17198725
TI  - Immune memory, immune oblivion: a lesson from Funes the memorious.
AB  - We commonly think of the immune system as having a memory. However, memory is
      always accompanied by a complementary process of oblivion. Is there immune
      oblivion? In this theoretical paper, I address this question and suggest that
      oblivion is an integral aspect of memorization. In this context, I suggest that
      immune memory is an orchestration of reversible and irreversible processes of
      biological computation through feedback loops. Drawing on the linguistic
      metaphor, I inquire into the implications of this idea for a better understanding
      of immune memory and immune deficiency among the elderly.

PMID- 17198726
TI  - Re: "En bloc resection of diaphragm with lung for recurrent ovarian cancer: a
      case report".

PMID- 17198727
TI  - Placental expression and molecular characterization of aromatase cytochrome P450
      in the spotted hyena (Crocuta crocuta).
AB  - At birth, the external genitalia of female spotted hyenas (Crocuta crocuta) are
      the most masculinized of any known mammal, but are still sexually differentiated.
      Placental aromatase cytochrome P450 (P450arom) is an important route of androgen
      metabolism protecting human female fetuses from virilization in utero. Therefore,
      placental P450arom expression was examined in spotted hyenas to determine levels
      during genital differentiation, and to compare molecular characteristics between
      the hyena and human placental enzymes. Hyena placental P450arom activity was
      determined at gestational days (GD) 31, 35, 45, 65 and 95 (term, 110), and the
      relative sensitivity of hyena and human placental enzyme to inhibition by the
      specific inhibitor, Letrozole, was also examined. Expression of hyena P450arom in
      placenta was localized by immuno-histochemistry, and a full-length cDNA was
      cloned for phylogenetic analysis. Aromatase activity increased from GD31 to a
      peak at 45 and 65, apparently decreasing later in gestation. This activity was
      more sensitive to inhibition by Letrozole than was human placental aromatase
      activity. Expression of P450arom was localized to syncytiotrophoblast and giant
      cells of mid-gestation placentas. The coding sequence of hyena P450arom was 94%
      and 86% identical to the canine and human enzymes respectively, as reflected by
      phylogenetic analyses. These data demonstrate for the first time that hyena
      placental aromatase activity is comparable to that of human placentas when
      genital differentiation is in progress. This suggests that even in female spotted
      hyenas clitoral differentiation is likely protected from virilization by
      placental androgen metabolism. Decreased placental aromatase activity in late
      gestation may be equally important in allowing androgen to program behaviors at
      birth. Although hyena P450arom is closely related to the canine enzyme, both
      placental anatomy and P450arom expression differ. Other hyaenids and carnivores
      must be investigated to determine the morphological and functional ancestral
      state of their placentas, as it relates to evolutionary relationships among
      species in this important taxonomic group.

PMID- 17198729
TI  - Neotic preferences in laboratory rodents: issues, assessment and substrates.
AB  - Neotic preference refers to the extent to which animals prefer stimuli of
      differing novelty value. Degree of novelty is determined by within- and between
      trials habituation and amount of temporal (novelty) and spatial change
      (complexity) in stimulation which in turn will determine the amount of curiosity
      based approach (neophilia) or fear-based avoidance (neophobia) of novel stimuli.
      Tests of genuine neotic preferences enable direct assessments of responsiveness
      to temporal and spatial changes and include measurements of novel versus familiar
      locations (such as novelty-related location preferences), responsiveness to
      stimulus complexity (such as object exploration) and learning for exploratory
      rewards (such as light-contingent bar-pressing). Effects of brain lesions and
      peripherally administered drugs have implicated several brain areas and
      neurotransmitters that subserve memory, fear and reward in neotic preferences
      namely the hippocampus and ACh (memory), the amygdala, GABA and 5-HT (fear), and
      the mesolimbic DA reward system. However, more attention should be paid to the
      complexity of interactions between different brain and neurotransmitter systems
      and improvements in methodology before conclusions should be drawn about the
      neurobiological basis of neotic preferences.

PMID- 17198728
TI  - Complex expression pattern of Wnt ligands and frizzled receptors in human
      placenta and its trophoblast subtypes.
AB  - Canonical Wingless (Wnt) signalling provoked by exogenous and endogenous Wnt
      ligands was recently shown to play a crucial role in the invasive differentiation
      of human trophoblasts. To gain insights into the expression pattern of the
      developmental regulators, we analysed all human Wnt ligands and their frizzled
      (FZD) receptors in the human placenta and different trophoblast model systems
      using semi-quantitative PCR. Fourteen out of 19 Wnt ligands and 8 out of 10 FZD
      receptors were detectable in placental tissues, however, expression patterns
      varied with gestational age and between different trophoblast subtypes suggesting
      cell-specific functions. Besides Wnt ligands acting through the canonical
      pathway, non-canonical ligands such as Wnt-5a, which may also activate
      alternative Wnt signalling pathways or inhibit canonical Wnt signalling, could be
      identified. Western blot analyses revealed secretion of Wnt-5a from primary
      trophoblast cultures and trophoblastic cell lines. To evaluate the potential role
      of Wnt-5a, SGHPL-5 trophoblast cells were transfected with luciferase reporter
      plasmids harbouring eight T-cell factor (TCF) DNA-recognition sequences which are
      exclusively activated through the canonical Wnt signalling pathway. Luciferase
      assays revealed that Wnt-3a-induced reporter activity was repressed by
      recombinant Wnt-5a indicating an antagonistic role in trophoblasts. The data
      suggest that a complex network of Wnt ligands and FZD receptors may regulate
      developmental processes of the human placenta.

PMID- 17198730
TI  - Evaluation of the usefulness of bird feathers as a non-destructive biomonitoring
      tool for organic pollutants: a comparative and meta-analytical approach.
AB  - In this study, we investigated whether bird feathers can be used as a non
      destructive biomonitor for organic pollutants. We analysed the outermost tail
      feathers of 8 terrestrial and aquatic bird species from Belgium (8 species,
      n=108) for polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers
      (PBDEs) and organochlorine pesticides (OCPs). Every compound class could be
      quantified in one single tail feather of the birds under study (sum PCBs ranging
      from 5.5 to 510 ng/g feather, sum PBDEs from 0.33 to 53 ng/g feather, sum DDTs
      from 1.5 to 730 ng/g feather), except for PBDEs in feathers of the common moorhen
      (Gallinula chloropus). Further, we calculated Pearson correlations between
      concentrations of organic pollutants in feathers and concentrations in
      corresponding muscle or liver tissue from the birds. Correlations were found
      significant in half of the cases of the terrestrial species, but were found not
      significant for the aquatic species, with the exception of a significant
      correlation of sum PCBs in the common moorhen. Only for the common buzzard (Buteo
      buteo) (n=43) all correlations were found significant (0.32<r<0.77). In order to
      cope for low statistical power, we performed a meta-analysis on all bird species
      together. This led to significant correlations between levels in feathers and
      corresponding levels in muscle or liver for all terrestrial birds (p<0.05 in all
      cases, effect size 0.59 (p,p'-DDE) to 0.71 (Sigma PCB) for levels in feather and
      muscle). When correlations were recalculated excluding the birds that had died
      due to starvation, correlation coefficients for the terrestrial birds were found
      even higher (effect size up to 0.83 (Sigma PCB)). These results have important
      implications for non-destructive and retrospective biomonitoring. Although our
      results suggest that exact concentrations in the body cannot be predicted using
      feathers, bird feathers can give a good estimate of contamination levels in a
      population and as such are a potential non-destructive biomonitoring tool for
      organic pollutants. Outermost tail feathers and muscle tissue were also examined
      for nitrogen (delta15N) and carbon (delta13C) stable isotope content in the
      different bird species. However, delta15N/delta13C signatures in feather or
      muscle were not significantly correlated with the corresponding levels of organic
      pollutants in these tissues. Various confounding factors (such as habitat,
      condition, age, sex) may have masked a relationship between delta15N values and
      organic pollutant levels in the birds under study.

PMID- 17198731
TI  - Treatment of Mooren's ulcer with topical administration of interferon alfa 2a.
AB  - OBJECTIVE: To report an apparently beneficial effect of topical interferon alfa
      2a (IFNalpha2a) as a single therapeutic agent in the treatment of Mooren's ulcer.
      DESIGN: Two case reports. PARTICIPANTS: Two consecutive patients with unilateral
      Mooren's ulcer diagnosed at the cornea service of Gulhane Military Medical
      Academy from December 2004 to December 2005 were studied retrospectively.
      INTERVENTION: Patients with a clinical diagnosis of Mooren's ulcer were treated
      with topical IFNalpha2a until their lesions resolved. MAIN OUTCOME MEASURES: A
      review of medical records was performed to assess the duration and response to
      treatment with topical IFNalpha2a drops, defined by clinical resolution of
      Mooren's ulcer. RESULTS: Symptoms and signs in 2 eyes improved during the first
      week of treatment, and reepithelialization was achieved at 7 and 10 days. Visual
      acuity levels reached 20/25 and 20/30 within 1 month of treatment. No recurrences
      were observed during 1 year and 6 months of follow up. CONCLUSIONS: Topical
      IFNalpha2a as a single therapeutic agent was an effective alternative in the
      treatment of our 2 patients with Mooren's ulcer. It offers the benefits of
      topical therapy and avoided surgical or other interventions that may lead to stem
      cell deficiency. Larger controlled studies are necessary to confirm the long-term
      efficacy and safety of this treatment.

PMID- 17198732
TI  - Oral step-down therapy is comparable to intravenous therapy for Staphylococcus
      aureus osteomyelitis.
AB  - BACKGROUND: We hypothesized that regimens with an early switch to oral
      antibiotics are as effective as prolonged parenteral regimens for staphylococcal
      osteomyelitis. METHODS: We retrospectively reviewed records of adult patients
      with osteomyelitis caused by Staphylococcus aureus as determined by sterile site
      cultures, who had at least 6 months of follow-up post-therapy. The population was
      divided into two treatment groups: (1) an intravenous group (i.v.) that received
      > or = 4 weeks of parenteral therapy, and (2) a switch group that received < 4
      weeks of intravenous followed by oral therapy. RESULTS: A total of 72 patients
      (36 in each group) were identified with groups evenly matched for demographic and
      clinical characteristics. The overall apparent cure rate was 74%; 69% for the
      i.v. group and 78% for the switch group (P=0.59). Apparent cure rates were
      similar regardless of duration of intravenous therapy: 83% < 2 weeks, 72% 2-4
      weeks, 75% 4-6 weeks and 66% > or = 6 weeks (P=0.68). Among the 39 patients who
      received rifampin-based combinations, those treated simultaneously with
      vancomycin and rifampin did significantly worse than those who received other
      rifampin combinations (P<0.02). Overall, MRSA infections responded poorly
      compared to MSSA (65% apparently cured versus 83%). However, 11/14 (79%) MRSA
      patients who received rifampin combinations, other than vancomycin and rifampin
      simultaneously, were apparently cured. CONCLUSIONS: Overall outcomes did not
      differ significantly between i.v. and switch groups. Given the markedly lower
      costs and ease of administration, prolonged oral regimens after initial
      intravenous therapy may be a preferred regimen for staphylococcal osteomyelitis.

PMID- 17198733
TI  - Viral infections of the central nervous system in Brazil.
AB  - OBJECTIVE: Epidemiological studies have shown that most central nervous system
      (CNS) infections are viral. The objective of this study is to contribute to the
      knowledge base concerning viral CNS infections in Ribeirao Preto, Brazil.
      METHODS: Two hundred cerebrospinal fluid (CSF) samples were taken from patients
      with clinically suspected viral CNS infection and analyzed for herpesvirus,
      enterovirus, alphavirus and flavivirus using PCR assays. RESULTS: Viral genome
      was detected in 43 CSF samples (23.34%): 6% cytomegalovirus (CMV), 5% herpes
      simplex virus type 1 (HSV-1), 0.5% each varicella-zoster virus (VZV) and Epstein
      Barr virus (EBV), and 11.34% enterovirus. Co-infections (CMV-enterovirus and CMV
      HSV-1) were found in 3 patients. CSF parameters such as cytology and protein
      level were normal in many patients with viral genome-positive CSF. CONCLUSIONS:
      Data obtained in this study contribute to the knowledge base concerning viral CNS
      infections in Brazil. This information will have a major impact on the clinical
      management of patients with CNS disease.

PMID- 17198734
TI  - The role of T helper cells in neuroprotection and regeneration.
AB  - The inflammatory wound healing response of the central nervous system (CNS)
      following mechanical injury is characterized by at least one or two phases of T
      cell infiltration. Surprisingly, whether T cells play a beneficial or detrimental
      role in these processes is still controversial. It has been suggested that
      autoimmune T cells may provide "protective autoimmunity", however, after CNS
      injury, injections of autoimmune T cells and vaccine strategies led to both
      improvement in some models and exacerbation of the damage in others. Here, we
      review increasing evidence that a specific T cell subpopulation, namely T helper
      cells type 2 (Th2 cells) are particularly beneficial in the context of CNS
      lesions. CNS injuries such as mechanical lesions or stroke induce a systemic
      immunosuppression, which is characterized by a systemic shift towards a Th2
      cytokine pattern. Simplified, this systemic Th2 shift results in reduced cell
      mediated immune responses, and, to a lesser extent, humoral immune responses.
      Furthermore, treatment with potent Th2 inducers such as glatiramer acetate or
      statins, as well as vaccination strategies using Th2-inducing adjuvants for
      immunization such as aluminum hydroxide, result in increased neuroprotection and
      regeneration -- without development of autoimmune CNS inflammation. Thus, it is
      tempting to speculate that a systemic Th2 shift is part of a necessary CNS wound
      healing response after injury, by furthering regeneration and preventing
      autoimmune disease of the CNS. Within this context, investigating the potential
      of a systemic Th2 shift to improve outcome after CNS injury, including the
      control of possible side-effects such as increased susceptibility to infection
      and allergic responses, is extremely promising.

PMID- 17198735
TI  - Antigen therapy of experimental autoimmune encephalomyelitis selectively induces
      apoptosis of pathogenic T cells.
AB  - Administration of high-dose myelin antigen induces massive T cell apoptosis in
      experimental autoimmune encephalomyelitis (EAE) but the nature of the target
      cells remains elusive. Here we have used a cell line established in eGFP
      transgenic Lewis rats to distinguish between pathogenic and bystander T cells in
      adoptive transfer EAE. Intravenous application of gpMBP strongly reduced the
      amount of encephalitogenic cells in spinal cord and spleen while the number of
      the other T cells remained constant. This could be attributed to their
      differential sensitivity to apoptosis. Thus, antigen therapy selectively targets
      pathogenic T cells and should therefore limit potential adverse effects.

PMID- 17198736
TI  - Identification of c-myc coding region determinant RNA sequences and structures
      cleaved by an RNase1-like endoribonuclease.
AB  - The coding region of c-myc mRNA encompassing the coding region determinant (CRD)
      nucleotides (nts) 1705-1792 is critical in regulating c-myc mRNA stability. This
      is in part due to the susceptibility of c-myc CRD RNA to attack by an
      endoribonuclease. We have previously purified and characterized a mammalian
      endoribonuclease that cleaves c-myc CRD RNA in vitro. This enzyme is tentatively
      identified as a 35 kDa RNase1-like endonuclease. In an effort to understand the
      sequence and secondary structure requirements for RNA cleavage by this enzyme, we
      have determined the secondary structure of the c-myc CRD RNA nts 1705-1792 using
      RNase probing technique. The secondary structure of c-myc CRD RNA possesses five
      stems; two of which contain 4 base pairs (stems I and V) and three consisting of
      3 base pairs (stems II, III, and IV). Endonucleolytic assays using the c-myc CRD
      and several c-myc CRD mutants as substrates led to the following conclusions: (i)
      the enzyme prefers to cleave in between the dinucleotides UA, CA, and UG in
      single-stranded regions; (ii) the enzyme is more specific towards UA
      dinucleotides. These properties further distinguish the enzyme from previously
      described mammalian endonuclease that cleaves c-myc mRNA in vitro.

PMID- 17198737
TI  - Mitochondrial targeting of farnesyl diphosphate synthase is a widespread
      phenomenon in eukaryotes.
AB  - The isoprenoid pathway is responsible for the generation of a wide range of
      products that are crucial for cellular processes; namely, cholesterol synthesis,
      protein glycosylation, growth control and synthesis of several hormones. Farnesyl
      diphosphate synthase (FPS), a key enzyme in this pathway, is usually considered
      to be cytosolic/peroxisomal. However, significant enzymatic activity has also
      been detected in rat liver mitochondria, although none of the mammalian FPS genes
      characterized to date contain sequences coding for mitochondrial transit
      peptides. Here, we describe the genomic organization of the human FPS gene and
      demonstrate that one of the two mRNAs expressed from this gene encodes an isoform
      with a 66 amino acid N-terminal extension containing a peptide that targets it to
      mitochondria. Previous studies suggested that the N-terminal extension of FPS in
      the plant Arabidopsis thaliana contains a mitochondrial targeting sequence. In
      this study, database analysis reveals that this is also the case in a number of
      mammals and insects. Finally, we provide functional proofs that the N-terminal
      sequence of Drosophila melanogaster FPS targets the protein to mitochondria.
      Taken together, these data suggest that mitochondrial targeting of FPS may be
      widespread among eukaryotes.

PMID- 17198738
TI  - Postoperative pulmonary arteriovenous fistula resulting in recurrent cryptogenic
      stroke.
AB  - We report on a 66-year-old patient with a history of two cryptogenic strokes and
      a patent foramen ovale (PFO) who received a transcatheter closure of his PFO in
      our institution, but shortly after the intervention there was still a relevant
      right-to-left shunt. The following work-up showed an isolated pulmonary
      arteriovenous fistula as the real cause for the right-to-left shunt and hence the
      two strokes.

PMID- 17198739
TI  - Antibiotic resistance of lactic acid bacteria and Bifidobacterium spp. isolated
      from dairy and pharmaceutical products.
AB  - The outlines of antibiotic resistance of some probiotic microorganisms were
      studied. This study was conducted with the double purpose of verifying their
      ability to survive if they are taken simultaneously with an antibiotic therapy
      and to increase the selective properties of suitable media for the isolation of
      samples containing mixed bacterial populations. We isolated from commercial dairy
      and pharmaceutical products, 34 strains declared as probiotics, belonging to the
      genera Bifidobacterium and Lactobacillus, and 21 strains of starter culture
      bacteria. All the microorganisms have been compared by electrophoresis of the
      soluble proteins for the purpose of identifying them. A Multiplex-PCR with genus-
      and species-specific primers was used to detect for Bifidobacterium animalis
      subsp. lactis presence. All bifidobacteria were B. animalis subsp. lactis except
      one Bifidobacterium longum. Sometimes the identification showed that the used
      strain was not the one indicated on the label. The lactobacilli were
      Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus delbrueckii
      subsp. bulgaricus. The streptococci were all Streptococcus thermophilus. The
      minimal inhibitory concentration (MIC) of 24 common antibiotic substances has
      been valued by the broth microdilution method. All tested strains were
      susceptible to ampicillin, bacitracin, clindamycin, dicloxacillin, erytromycin,
      novobiocin, penicillin G, rifampicin (MIC(90) ranging from 0.01 to 4 microg/ml);
      resistant to aztreonam, cycloserin, kanamycin, nalidixic acid, polymyxin B and
      spectinomycin (MIC(90) ranging from 64 to >1000 microg/ml). The susceptibility to
      cephalothin, chloramphenicol, gentamicin, lincomycin, metronidazole, neomycin,
      paromomycin, streptomycin, tetracycline and vancomycin was variable and depending
      on the species.

PMID- 17198740
TI  - The multi-step process of human skin carcinogenesis: a role for p53, cyclin D1,
      hTERT, p16, and TSP-1.
AB  - As proposed by Hanahan and Weinberg (2000. Cell 100, 57-70) carcinogenesis
      requires crucial events such as (i) genomic instability, (ii) cell cycle
      deregulation, (iii) induction of a telomere length maintenance mechanism, and
      (iv) an angiogenic switch. By comparing the expression of p53, cyclin D1, p16,
      hTERT, and TSP-1 in spontaneously regressing keratoacanthoma (KA) as a paradigm
      of early neoplasia, with malignant invasive cutaneous squamous cell carcinoma
      (SCC) as a paradigm of advanced tumour development, we are now able to assign the
      changes in the expression of these proteins to specific stages and allocate them
      to defined roles in the multi-step process of skin carcinogenesis. We show that
      mutational inactivation of the p53 gene, and with that the onset of genomic
      instability is the earliest event. Individual p53-positive cells are already seen
      in "normal" skin, and 3/5 actinic keratoses (AKs), 5/22 KAs, and 13/23 SCCs
      contain p53-positive patches. Cell cycle deregulation was indicated by the
      overexpression of the cell cycle regulator cyclin D1, as well as by the loss of
      the cell cycle inhibitor p16. Interestingly, overexpression of cyclin D1 -
      observed in 80% of KAs and SCCs, respectively - showed a cell cycle-independent
      function in HaCaT cell transplants on nude mice. Cyclin D1 overexpression was
      associated with a massive inflammatory response, finally leading to tissue
      destruction. Loss of the cell cycle inhibitor p16, on the other hand, correlated
      with SCCs. Thus, it is tempting to suggest that overexpression of cyclin D1 is an
      early change that in addition to growth stimulation leads to an altered
      epithelial-mesenchymal interaction, while functional p16 is able to control this
      deregulated growth and needs to be eliminated for malignant progression. Another
      requirement for uncontrolled growth is the inhibition of telomere erosion by up
      regulating telomerase activity. As measured by hTERT protein expression, all of
      the KAs and SCCs studied were positive, with a similar distribution of the
      protein in both groups and an expression pattern resembling that of normal
      epidermis. Thus, telomerase may not need to be increased significantly in skin
      carcinomas. Finally, we show that the angiogenesis inhibitor TSP-1 is strongly
      expressed in most KAs, and mainly by the tumour cells, while in SCCs the
      generally weak expression is restricted to the tumour-stroma. Furthermore, we
      provide evidence that the loss of a copy of chromosome 15 is responsible for
      reduced TSP-1 expression and thereby this aberration contributes to tumour
      vascularisation (i.e. the angiogenic switch) required for malignant growth.

PMID- 17198741
TI  - Bilateral parotid enlargement due to malnutrition under the influence of the
      media in an adolescent in Lithuania.
AB  - The elimination of censorship for the media in post-communist countries in
      transition has contributed to increases in the prevalence of several medical
      problems. Children and adolescents are particularly vulnerable to the messages
      conveyed through the media, which influence their perceptions and behaviour. We
      describe a case of bilateral parotid enlargement due to malnutrition under the
      influence of self-prescribed diet in an adolescent. A 15-year-old girl reported
      to our institution under suspicion of Sjogren's syndrome for medical advice. Two
      months ago she developed persistent bilateral parotid enlargement and a dry
      mouth. Her medical history revealed a weight loss due to "self-prescribed" reduce
      diet. Social questioning clarified high use of the media and influence on the
      body concept and self image. On extra oral examination, a diffuse parotid
      enlargement was seen bilaterally. The examination of the mouth showed a low
      moisture level of the intraoral mucosa. The unstimulated whole salivary flow rate
      was 2 ml in 15 min. Laboratory findings evidenced anemia (107 g/l). The serum
      albumin concentration indicated a reduced level (28 g/l). Search for antinuclear
      antibodies, anti-SSA antibodies, anti-SSB, -Sm, -RNP and anti-double-stranded DNA
      antibodies was negative. Evaluation for antibodies against hepatitis C,
      cytomegalovirus and Epstein-Barr virus infection and HIV rendered negative
      results. A histopathologic examination of labial salivary gland biopsy revealed a
      picture of sialoadenosis. From the above investigations, a diagnosis of
      sialoadenosis due to malnutrition was made.

PMID- 17198742
TI  - A cost-utility analysis of multivitamin and multimineral supplements in men and
      women aged 65 years and over.
AB  - BACKGROUND & AIMS: As people age there is a progressive dysregulation of the
      immune system that may lead to an increased risk of infections, which may
      precipitate hospital admission in people with chronic heart or respiratory
      diseases. Mineral and vitamin supplementation in older people could therefore
      influence infections in older people. However, the evidence from the available
      randomised controlled trials (RCTs) is mixed. The aim of the study was to assess
      the relative efficiency of multivitamin and multimineral supplementation compared
      with no supplementation. METHODS: Cost-utility analysis alongside an RCT.
      Participants aged 65 years or over from six general practices in Grampian,
      Scotland, were studied. They were randomised to one tablet daily of either a
      multivitamin and multimineral supplement or matching placebo. Exclusion criteria
      were use of mineral, vitamin or fish oil supplements in the previous 3 months (1
      month for water soluble vitamins), vitamin B12 injection in the last 3 months.
      RESULTS: Nine hundred and ten participants were recruited (454 placebo and 456
      supplementation). Use of health service resources and costs were similar between
      the two groups. The supplementation arm was more costly although this was not
      statistically significant ( pound15 per person, 95% CI-3.75 to 34.95). After
      adjusting for minimisation and baseline EQ-5D scores supplementation was
      associated with fewer QALYs per person (-0.018, 95% CI-0.04 to 0.002). It was
      highly unlikely that supplementation would be considered cost effective.
      CONCLUSIONS: The evidence from this study suggests that it is highly unlikely
      that supplementation could be considered cost effective.

PMID- 17198743
TI  - Short nucleotide polymorphic insertions in the MCL-1 promoter affect gene
      expression.
AB  - We have recently reported novel short nucleotide (six and eighteen) polymorphic
      insertions, in the MCL-1 promoter and their association with higher mRNA and
      protein levels. The aim of the present study was to test the hypothesis that
      these insertions directly affect MCL-1 gene expression. Haematopoietic and
      epithelial human cell lines were transfected with +0, +6, or +18 MCL-1 promoter
      fragments positioned upstream of the Firefly luciferase reporter gene. The cells
      were stimulated with phorbol 12-myristate 13-acetate (PMA) and granulocyte
      macrophage colony-stimulating factor (GM-CSF). Compared to +0, both polymorphic
      insertions (+6 and +18) were associated with increased promoter activity.
      Although chromatin immunoprecipitation assay showed that there are Sp1/Sp3
      binding sites in the MCL-1 promoter, electrophoretic mobility shift assay showed
      that it is unlikely that these sites are in the region harboring these
      insertions. These results provide further evidence for the biological effect of
      MCL-1 promoter polymorphisms on gene expression.

PMID- 17198744
TI  - Daily hassles and eating behaviour: the role of cortisol reactivity status.
AB  - Previous research has shown high cortisol reactors to consume a greater amount of
      snack foods than low reactors following a laboratory stressor. The current study
      tested whether high cortisol reactors also consume more snacks than low reactors
      in response to field stressors. Fifty pre-menopausal women completed a laboratory
      stressor, provided saliva samples to assess cortisol reactor status and then
      completed daily hassles and snack intake diaries over the next fourteen days.
      Hierarchical multivariate linear modelling showed a significant association
      between daily hassles and snack intake within the overall sample, where an
      increased number of hassles was associated with increased snack intake. This
      significant positive association between number of hassles and snack intake was
      only observed within the high cortisol reactors and not within the low cortisol
      reactors. These findings suggest that high cortisol reactivity to stress promotes
      food intake. Furthermore, the eating style variables of restraint, emotional
      eating, external eating and disinhibition were more strongly associated with
      snack intake in high reactors than in low reactors. This suggests that cortisol
      reactivity may in part account for the moderating role of eating style on stress
      induced eating. The results are discussed within the context of future health
      risk.

PMID- 17198745
TI  - Cortisol hypersecretion in unipolar major depression with melancholic and
      psychotic features: dopaminergic, noradrenergic and thyroid correlates.

PMID- 17198746
TI  - The mouse Trm1-like gene is expressed in neural tissues and plays a role in motor
      coordination and exploratory behaviour.
AB  - Using a gene trap approach in ES cells, the novel mouse gene Trm1-like with
      substantial sequence homology to human C1orf25 mRNA (GenBank accession no. ) was
      identified. Murine Trm1-like encodes a putative protein with limited similarity
      to N2,N2-dimethylguanosine tRNA methyltransferase (Trm1) from other organisms,
      however its function is not known. The potential role of Trm1-like was
      investigated in a mouse mutant lacking intact Trm1-like transcripts due to
      integration of the gene trap vector in the first intron. Trm1-like deficient mice
      are viable and show no apparent anatomical defects. Behavioural tests, however,
      revealed significantly altered motor coordination and aberrant exploratory
      behaviour. LacZ activity of the trapped mouse Trm1-like gene reflects expression
      in various neuronal structures during embryonic development, including spinal
      ganglia, trigeminal nerve and ganglion, olfactory and nasopharyngeal epithelium,
      and nuclei of the metencephalon, thalamus and medulla oblongata. The gene is also
      expressed in lung, oesophagus, epiglottis, ependyma, vertebral column, spinal
      cord, and brown adipose tissue. Trm1-like expression persists in the adult brain
      with dynamically changing patterns in cortex and cerebellum. Although Trm1-like
      is not essential for embryonic mouse development, it may have a role in
      modulating postnatal neuronal functions.

PMID- 17198747
TI  - The effect of glucosamine concentration on the development and sex ratio of
      bovine embryos.
AB  - Glucosamine is a component of hyaluronic acid and an alternative substrate to
      glucose for the extracellular matrix synthesis of COCs. Its addition to an IVM
      medium reduces the glucose consumption of bovine COCs. Glucosamine is also
      metabolized to UDP-N-acetyl glucosamine (UDP-GlcNAc) via the hexosamine
      biosynthesis pathway and is utilized for O-linked glycosylation by the X-linked
      enzyme, O-linked GlcNAc transferase (OGT). Moreover, the inactivation of the
      second X chromosome in female embryos is influential in producing the sex ratio
      bias observed in vitro when embryos are cultured in the presence of glucose above
      2.5mM. Accordingly, the aim of this study is to examine whether the presence of
      glucosamine during maturation or embryo culture causes a sex ratio bias in bovine
      blastocysts. Glucosamine was added to the medium in three different embryo
      developmental periods: in vitro maturation, the one-cell to eight-cell stage
      (before the maternal-zygotic transition, MZT), and the eight-cell to blastocyst
      stage (after MZT). When glucosamine was added during in vitro maturation, the
      developmental competence of oocytes was severely compromised. However, the sex
      ratio of embryos was not influenced. When glucosamine was added to embryo culture
      medium during development from one-cell to eight-cell stage (before MZT), it
      affected neither the development nor the sex ratio of bovine embryos. Finally,
      when glucosamine was added after MZT, the development rate of embryos was
      severely decreased, and the sex ratio was skewed toward males. Moreover, an
      inhibitor of OGT, benzyl-2-acetamido-2-deoxy-alpha-D-galactopyranoside (BADGP),
      negated the effect of glucosamine on the sex ratio when it was added to embryo
      culture medium from the eight-cell to blastocyst stage (after MZT). These results
      suggest that, like glucose, the supplementation of glucosamine into the medium
      skewed the sex ratio to males and that OGT, an X-linked enzyme, was involved in
      this phenomenon. Moreover, this effect of glucosamine was limited only to when it
      was present in the embryo culture medium after MZT.

PMID- 17198748
TI  - Induction of matrix metalloproteinases (MMP3, MMP12 and MMP13) expression in the
      microglia by amyloid-beta stimulation via the PI3K/Akt pathway.
AB  - Alzheimer's disease is characterized by the presence of senile plaques in the
      brain composed primarily of amyloid-beta peptide. Microglia have been reported to
      surround these Abeta plaques, which have opposite roles, provoking a microglia
      mediated inflammatory response that contributes to neuronal cell loss or the
      removal of Abeta and damaged neurons. We herein analyzed the process of
      expression of Matrix metalloproteinases induced by Abeta stimulation. We found
      that Abeta1-42 induces a high level of MMP3, MMP12 and MMP13 in the microglia.
      The signal transduction pathway for the expression of these MMPs mRNA induced by
      Abeta1-42 depends on PI3K/Akt.

PMID- 17198750
TI  - Prolactin, menstrual irregularities, quality of life.

PMID- 17198749
TI  - Protein hormones and immunity.
AB  - A number of observations and discoveries over the past 20 years support the
      concept of important physiological interactions between the endocrine and immune
      systems. The best known pathway for transmission of information from the immune
      system to the neuroendocrine system is humoral in the form of cytokines, although
      neural transmission via the afferent vagus is well documented also. In the other
      direction, efferent signals from the nervous system to the immune system are
      conveyed by both the neuroendocrine and autonomic nervous systems. Communication
      is possible because the nervous and immune systems share a common biochemical
      language involving shared ligands and receptors, including neurotransmitters,
      neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means
      that the brain functions as an immune-regulating organ participating in immune
      responses. A great deal of evidence has accumulated and confirmed that hormones
      secreted by the neuroendocrine system play an important role in communication and
      regulation of the cells of the immune system. Among protein hormones, this has
      been most clearly documented for prolactin (PRL), growth hormone (GH), and
      insulin-like growth factor-1 (IGF-I), but significant influences on immunity by
      thyroid-stimulating hormone (TSH) have also been demonstrated. Here we review
      evidence obtained during the past 20 years to clearly demonstrate that
      neuroendocrine protein hormones influence immunity and that immune processes
      affect the neuroendocrine system. New findings highlight a previously
      undiscovered route of communication between the immune and endocrine systems that
      is now known to occur at the cellular level. This communication system is
      activated when inflammatory processes induced by proinflammatory cytokines
      antagonize the function of a variety of hormones, which then causes endocrine
      resistance in both the periphery and brain. Homeostasis during inflammation is
      achieved by a balance between cytokines and endocrine hormones.

PMID- 17198751
TI  - Antioxidant modulation of oxidant-stimulated uptake and release of arachidonic
      acid in eicosapentaenoic acid-supplemented human lymphoma U937 cells.
AB  - Omega-3 polyunsaturated fatty acids (PUFA) are increasingly finding use as
      treatments for a variety of medical conditions. PUFA supplementation can,
      however, result in increased oxidative stress causing elevated turnover rate of
      membrane phospholipids, impairment of membrane integrity and increased formation
      of inflammatory mediators. The aim of this study was to determine which
      antioxidant compounds were most effective in ameliorating the stimulation of
      phospholipid turnover by oxidative stress. U937 cells were supplemented with
      eicosapentaenoic acid and either ascorbic acid, alpha-tocopherol, beta-carotene
      or astaxanthin prior to being challenged with oxidant. Although all antioxidants
      were found to be effective in decreasing oxidant-stimulated peroxide formation,
      only alpha-tocopherol significantly decreased oxidant-stimulated release of 3H
      labeled arachidonic acid (AA), while ascorbic acid markedly increased release.
      All antioxidants except alpha-tocopherol decreased oxidant-stimulated 3H-AA
      uptake. Our data suggest that antioxidants are not equally effective in combating
      the effects of oxidative stress upon membrane phospholipid turnover, and that
      optimal protection will require mixtures of antioxidants.

PMID- 17198752
TI  - Evaluation of sites for the location of WEEE recycling plants in Spain.
AB  - As a consequence of new European legal regulations for treatment of waste
      electrical and electronic equipment (WEEE), recycling plants have to be installed
      in Spain. In this context, this contribution describes a method for ranking of
      Spanish municipalities according to their appropriateness for the installation of
      these plants. In order to rank the alternatives, the discrete multi-criteria
      decision method PROMETHEE (Preference Ranking Organisation METHod for Enrichment
      Evaluations), combined with a surveys of experts, is applied. As existing plants
      are located in North and East Spain, a significant concentration of top ranking
      municipalities can be observed in South and Central Spain. The method does not
      present an optimal structure of the future recycling system, but provides a
      selection of good alternatives for potential locations of recycling plants.

PMID- 17198753
TI  - What general emergency nurses want to know about mental health patients
      presenting to their emergency department.
AB  - This paper presents the findings of a qualitative project conducted to
      investigate the education and training requirements that non-mental health
      trained emergency nurses need to enable them to effectively care for psychiatric
      patients presenting to a West Australian emergency department. Non-mental health
      trained nurses are ill-equipped in their psychiatric knowledge, assessment and
      communication skills to provide best possible care to the one in ten patients
      presenting to the emergency department with a complex mental health issue. The
      area of assessment and management of mental health patients in the emergency
      department is a complex one and staff are required to assess, triage and manage
      these patients appropriately. Furthermore, with aggression and violence
      increasing, emergency department nurses are concerned about their safety in the
      workplace. Focus groups with emergency nurses and semi-structured interviews with
      subject matter experts were conducted at one West Australian teaching hospital.
      The findings of the project demonstrated that these nurses considered that
      customer focus, workplace aggression and violence, psychiatric theory, mental
      health assessment and chemical dependence as key learning areas. These findings
      will form a platform for further education and training for ED staff.

PMID- 17198754
TI  - Intra-articular injection of the cyclooxygenase-2 inhibitor parecoxib attenuates
      osteoarthritis progression in anterior cruciate ligament-transected knee in rats:
      role of excitatory amino acids.
AB  - OBJECTIVE: Our present study examined the effect of intra-articular
      cyclooxygenase-2 (COX-2) inhibitor parecoxib on osteoarthritis (OA) progression
      and the concomitant changes in excitatory amino acids' (EAAs) levels of the
      anterior cruciate ligament-transected (ACLT) knee joint dialysates. METHODS: OA
      was induced in Wistar rats by anterior cruciate ligament transection of the knee
      of one hindlimb, the other was left unoperated and untreated. Rats were placed
      into four groups: Group ACLT/P received intra-articular parecoxib injection (100
      microg) in the ACLT knee once a week for 5 consecutive weeks starting at 8 weeks
      after surgery. Group ACLT/S received the same procedure as group ACLT/P with
      saline injection instead. Naive (Naive/P) rats received only intra-articular
      parecoxib injection in one knee once a week for 5 consecutive weeks without
      surgery. The sham-operated rats underwent arthrotomy only without treatment.
      Twenty weeks after surgery, knee joint dialysates were collected and EAAs'
      concentration was assayed by high-performance liquid chromatography, and gross
      morphology and histopathology (Mankin and synovitis grading) were examined on the
      medial femoral condyles and synovia. RESULTS: Parecoxib alone had no effect on
      cartilage and synovium of normal knees in Naive/P rats. In ACLT/P rats, parecoxib
      treatment showed a significant inhibition of cartilage degeneration of the medial
      femoral condyle at both the macroscopic level (1.15+/-0.17 vs 2.55+/-0.12,
      P<0.05) and the Mankin scores (3.03+/-0.28 vs 8.82+/-0.43, P<0.05). Intra
      articular parecoxib injection also suppressed the synovial inflammation of ACLT
      joint compared to the ACLT/S group (3.92+/-0.41 vs 9.25+/-0.32, P<0.05).
      Moreover, glutamate and aspartate levels were also significantly reduced in the
      ACLT/P group compared to the ACLT/S group by parecoxib treatment (91.2+/-9.4% vs
      189.5+/-17.0%, P<0.05 and 98.2+/-11.6% vs 175.3+/-12.4%, P<0.05, respectively).
      CONCLUSION: This study shows that intra-articular injection of COX-2 inhibitor
      parecoxib inhibits the ACLT-induced OA progression; it was accompanied by a
      reduction of glutamate and aspartate concentration in the ACLT joint dialysates.
      From our present results, we suggested that intra-articular parecoxib injection,
      in addition to the anti-inflammatory effect, inhibiting the EAAs' release, may
      also play a role in inhibiting the traumatic knee injury induced OA progression.

PMID- 17198755
TI  - Apoptosis affects integration frequency: adult stem cells injected in blastocysts
      show high caspase-3 activity.
AB  - Chimeric organisms are commonly generated by injecting stem cells into
      blastocysts. Embryonic stem cells injected into the blastocoel cavity participate
      in the further development of the embryo. Adult stem cells have also been used in
      injection experiments to study their potential plasticity. In this study we
      focused on the early fate of injected human adult hematopoietic stem cells
      (HSCs). HSCs were followed immunohistochemically 1-19 h after injection into
      murine blastocysts. We found that they only rarely attached and integrated into
      the blastocysts. The high rate of loss of injected cells after prolonged in vitro
      culture of the chimeras can be explained by apoptosis. Our findings are
      consistent with previous studies reporting a low rate of integration of adult
      cells injected to produce chimeric embryos, but this is the first demonstration
      that the low efficiency of adult stem cell injections into blastocysts is
      influenced by apoptosis.

PMID- 17198756
TI  - Medroxyprogesterone and tamoxifen augment anti-proliferative efficacy and reduce
      mitochondria-toxicity of epirubicin in FM3A tumor cells in vitro.
AB  - We have shown that low doses of medroxyprogesterone acetate (MPA- 2.6 microM) and
      tamoxifen (TAM- 270 nM) could augment the effectiveness of epirubicin in breast
      tumor cells. In this study, we monitored early cell kinetics (24-96 h plating and
      S-phase) and mitochondrial morphology during chemo-endocrine treatments to
      delineate the epirubicin sensitizing mechanism. S-phase fractions with
      radioactive thymidine uptake, plating efficacy, and transmission electron
      microscopic analysis were taken for 24-h periods until the 7th day after drug
      treatments. Despite strongly enhancing the clonogenic killing, both MPA and TAM
      did not affect epirubicin induced early cytotoxicity. Instead, they augmented the
      S-phase inhibition, which was even more pronounced for TAM. Epirubicin induced
      prominent swelling and crista damage of mitochondria and fragmentation of nuclei.
      Mitochondria were a normal size during a combination of epirubicin with either
      MPA- or tamoxifen treatment, despite the persistence of chromatin fragmentation
      and strong synergism on the clonogenic killing of breast tumor cells. Low dosage
      endocrine agent-induced anthracycline sensitization may be independent of
      mitochondrial toxicity. Further studies would be worthwhile, since the uncoupling
      of mitochondrial toxicity from the anti-neoplastic effect may also mean obviated
      cardiac toxicity in clinic.

PMID- 17198758
TI  - Potential mechanisms connecting asthma, esophageal reflux, and obesity/sleep
      apnea complex--a hypothetical review.
AB  - Obstructive sleep apnea (OSA) and asthma are potentially linked at several
      levels. The pathophysiology of these two conditions seems to overlap
      significantly, as airway obstruction, inflammation, obesity, and several other
      factors are implicated in the development of both diseases. Gastroesophageal
      reflux disease (GERD), cardiovascular complications, obesity itself, and the
      underlying inflammatory processes are all complex contributory factors that
      provide hypothetical links. Furthermore, a collateral rise in prevalence of both
      OSA and asthma has been noticed during the past few years, occurring in
      association with the emerging epidemic of obesity, a common risk factor for both
      conditions. OSA and asthma share many other risk factors as well. We propose a
      hypothetical OSA-asthma relationship that has implications on the diagnosis and
      management of patients presenting with either condition singly. Clinicians should
      be aware that OSA might complicate asthma management. Based on this hypothesis,
      we suggest that the treatment of the individual patient who experiences both
      asthma and OSA needs to be multidisciplinary and comprehensive. This hypothetical
      association of asthma and OSA, though described anecdotally, has not been
      systematically studied. In particular, the influence of continuous positive
      airway pressure therapy (for sleep apnea) on asthma outcomes (such as quality of
      life, steroid utilization, emergency room visits) and fatality needs to be
      studied further.

PMID- 17198759
TI  - Anaesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine
      and ketamine administered to telemetered cats.
AB  - The quality and duration of anaesthesia, cardiorespiratory effects and recovery
      characteristics of a morphine, medetomidine, ketamine (MMK) drug combination were
      determined in cats. Six healthy, adult female cats were administered 0.2 mg/kg
      morphine sulphate, 60 microg/kg medetomidine hydrochloride, and 5 mg/kg ketamine
      hydrochloride intramuscularly. Atipamezole was administered intramuscularly at
      120 min after MMK administration. Time to lateral recumbency, intubation,
      extubation and sternal recumbency were recorded. Cardiorespiratory variables and
      response to a noxious stimulus were recorded before and at 3 min and 10 min
      increments after drug administration until sternal recumbency. The time to
      lateral recumbency and intubation were 1.9+/-1.2 and 4.3+/-1.2 min, respectively.
      Body temperature and haemoglobin saturation with oxygen remained unchanged
      compared to baseline values throughout anaesthesia. Respiratory rate, tidal
      volume, minute volume, heart rate, and blood pressure were significantly
      decreased during anaesthesia compared to baseline values. One cat met criteria
      for hypotension (systolic blood pressure <90 mmHg). End tidal carbon dioxide
      increased during anaesthesia compared to baseline values. All but one cat
      remained non-responsive to noxious stimuli from 3 to 120 min. Time to extubation
      and sternal recumbency following atipamezole were 2.9+/-1.1 and 4.7+/-1.0 min,
      respectively. MMK drug combination produced excellent short-term anaesthesia and
      analgesia with minimal cardiopulmonary depression. Anaesthesia lasted for at
      least 120 min in all but one cat and was effectively reversed by atipamezole.

PMID- 17198760
TI  - Clinical and molecular analysis of GM2 gangliosidosis in two apparent littermate
      kittens of the Japanese domestic cat.
AB  - This case report documents clinical and molecular findings in two littermate
      kittens of the Japanese domestic cat with GM2 gangliosidosis variant 0. Analysis
      included detailed physical, magnetic resonance imaging, biochemical, pathological
      and genetic examinations. At first, these littermate kittens showed typical
      cerebellar signs at approximately 2 months of age. About 2 months later, they
      progressively showed other neurological signs and subsequently died at about 7
      months of age. Magnetic resonance imaging just before the death showed an
      enlarged ventricular system, T1 hyperintensity in the internal capsule, and T2
      hyperintensity in the white matter of the whole brain. Histological findings
      suggested a type of lysosomal storage disease. Biochemical studies demonstrated
      that the kittens were affected with GM2 gangliosidosis variant 0, and a DNA assay
      finally demonstrated that these animals were homozygous for the mutation, which
      the authors had identified in a different family of the Japanese domestic cat.
      The findings in the present cases provide useful information about GM2
      gangliosidosis variant 0 in Japanese domestic cats.

PMID- 17198761
TI  - Contribution of GM-CSF on the enhancement of the T cell-stimulating activity of
      macrophages.
AB  - Mycobacterium leprae is an intracellular parasitic organism that multiplies in
      macrophages (MO). It inhibits the fusion of mycobacterial phagosome with lysosome
      and induces interleukin (IL)-10 production from macrophages. However, macrophages
      are heterogenous in various aspects. We examined macrophages that differentiated
      from monocytes using either recombinant (r) granulocyte-MO colony-stimulating
      factor (GM-CSF) (these MO are named as GM-MO) or rMO colony-stimulating factor (M
      CSF) (cells named as M-MO) in terms of the T cell-stimulating activity. Although
      both macrophages phagocytosed the mycobacteria equally, GM-MO infected with M.
      leprae and subsequently treated with IFN-gamma- and CD40 ligand (L) stimulated T
      cells to produce interferon-gamma (IFN-gamma), but M-MO lacked the ability to
      stimulate T cells. While M-MO mounted a massive IL-10 production, GM-MO did not
      produce the cytokine on infection with M. leprae. M. leprae-infected, IFN-gamma-
      and CD40L-treated GM-MO expressed a higher level of HLA-DR and CD86 Ags than
      those of M-MO, and expressed one of the dominant antigenic molecules of M.
      leprae, Major Membrane Protein-II on their surface. These results indicate that
      GM-CSF, but not M-CSF, contributes to the up-regulation of the T cell-stimulating
      activity of M. leprae-infected macrophages.

PMID- 17198763
TI  - Rehabilitative ultrasound measurement of select trunk muscle activation during
      induced pain.
AB  - Rehabilitative ultrasound imaging (RUSI) is considered a valid method to measure
      muscle activation in key spinal muscles in asymptomatic subjects. Research
      measuring muscle activation with RUSI in painful subjects is limited. The aim of
      this study was to determine if changes in muscle activation from experimentally
      induced pain can be measured by RUSI. Six male subjects performed tasks known to
      activate the transverse abdominis (TrA) and lumbar multifidus (LM) while RUSI
      measurements of muscle thickness were obtained during control and hypertonic
      saline conditions. The abdominal draw-in maneuver was used to volitionally
      activate the TrA and a series of upper extremity lifting tasks were used to
      automatically activate the LM. Pain was induced by injecting 5% hypertonic saline
      into the longissimus muscle adjacent to the LM at the L4 level. The percent
      change in muscle thickness from rest to contraction represented muscle
      activation. Activation was significantly less (p<0.01) during the painful
      condition on 4 of the 5 tasks performed for the LM and on the task performed for
      the TrA. These results indicate that RUSI can be used to measure pain-related
      changes in deep trunk muscle activation. Future research should include a larger
      sample size and women.

PMID- 17198762
TI  - IL-23-dependent IL-17 production is essential in neutrophil recruitment and
      activity in mouse lung defense against respiratory Mycoplasma pneumoniae
      infection.
AB  - IL-23 induces IL-17 production in activated CD4+ T cells and participates in host
      defense against many encapsulated bacteria. However, whether the IL-23/IL-17 axis
      contributes to a Mycoplasma pneumoniae (Mp)-induced lung inflammation (e.g.,
      neutrophils) has not been addressed. Using an acute respiratory Mp infection
      murine model, we found significantly up-regulated lung IL-23p19 mRNA in the early
      phase of infection (4h), and alveolar macrophages were an important cell source
      of Mp-induced IL-23. We further showed that Mp significantly increased IL-17
      protein levels in bronchoalveolar lavage (BAL). Lung gene expression of IL-17, IL
      17C and IL-17F was also markedly up-regulated by Mp in vivo. IL-17 and IL-17F
      were found to be derived mainly from lung CD4+ T cells, and were increased upon
      IL-23 stimulation in vitro. In vivo blocking of IL-23p19 alone or in combination
      with IL-23/IL-12p40 resulted in a significant reduction of Mp-induced IL-17
      protein and IL-17/IL-17F mRNA expression, which was accompanied by a trend toward
      reduced lung neutrophil recruitment, BAL neutrophil activity, and Mp clearance.
      However, IL-23 neutralization had no effect on Mp-induced lung IL-17C mRNA
      expression. These results demonstrate that IL-17/IL-17F production is IL-23
      dependent in an acute Mp infection, and contributes to neutrophil recruitment and
      activity in the lung defense against the infection.

PMID- 17198764
TI  - Aquatic animal models of human disease.

PMID- 17198766
TI  - Controversies and challenges in defining the etiology and pathophysiology of
      restless legs syndrome.
AB  - Restless legs syndrome (RLS) can occur as a primary disorder, with no apparent
      cause other than a possible genetic predisposition, or as a secondary condition,
      most commonly related to iron deficiency, pregnancy, or end-stage renal disease.
      Recent studies have identified 2 different phenotypes of RLS based on age at
      onset of symptoms. Persons whose RLS symptoms start at an earlier age (<45 years)
      are more likely to have a family history of RLS and tend to have a more slowly
      progressive development of the disorder compared with individuals who have later
      onset of symptoms. In the past, our ability to determine either prevalence or
      population factors associated with increased occurrence of RLS has been limited.
      However, 4 different diagnostic criteria have been established. Familiarity with
      diagnostic criteria and clinical characteristics are essential for diagnosis and
      appropriate treatment, if required.

PMID- 17198767
TI  - Current guidelines and standards of practice for restless legs syndrome.
AB  - Algorithms for treatment of restless legs syndrome (RLS) include both
      nonpharmacologic and pharmacologic therapy. Patients with RLS are divided into 3
      groups: (1) those with intermittent RLS symptoms; (2) those with daily RLS
      symptoms; and (3) those whose symptoms are refractory to standard treatments.
      Many patients do not require medication, and symptoms often can be relieved with
      good sleep hygiene and avoidance of medications and factors that provoke
      symptoms. Recent large-scale clinical trials have proved the efficacy of therapy
      for RLS when it is required. Several classes of medications are helpful, but
      dopaminergic therapy appears to be most effective and relieves symptoms rapidly.
      The first step in managing RLS is to ensure that there is an adequate diagnosis;
      this involves discriminating RLS from other conditions that may share a number of
      features. Finally, it is important to tailor treatment to the needs of each
      individual patient.

PMID- 17198768
TI  - A better future for patients with restless legs syndrome.
AB  - Despite advances in the management of restless legs syndrome (RLS), there still
      is a great deal of uncertainty about its etiology, pathophysiology, therapy, and
      clinical outcomes. Much remains to be learned. Future research on these issues
      will help identify the optimum therapeutic approach for the diverse group of
      patients with RLS.

PMID- 17198769
TI  - Clinical presentation, diagnosis, and quality of life issues in restless legs
      syndrome.
AB  - Restless legs syndrome (RLS) is a generally underdiagnosed and undertreated
      condition. It is a common cause of sleep disturbance that can severely disrupt
      normal life functioning. However, because of the failure to recognize RLS as a
      distinct disorder, clinicians have minimized the significance of the morbidity
      experienced by some patients. A positive family history is present in >50% of
      patients with RLS. Indeed, a person with RLS is 3 to 6 times more likely to have
      a positive family history of RLS than is an individual who does not have the
      disease. The differential diagnosis of RLS includes both movement and sleep
      disorders. Establishing an accurate diagnosis is crucial because effective
      treatment is available. In 2002, RLS experts revised diagnostic criteria and
      established 4 essential criteria for the diagnosis. Assessing the most bothersome
      symptoms and quantifying the severity of RLS are important because not all
      patients require medical therapy. Moreover, therapy may vary according to which
      symptom represents the major problem.

PMID- 17198770
TI  - Wide splitting of the second heart sound and systolic murmur: not what you think.

PMID- 17198771
TI  - Off-pump coronary artery bypass sacrifices graft patency: meta-analysis of
      randomized trials.

PMID- 17198772
TI  - On-pump versus off-pump coronary artery bypass grafting.

PMID- 17198773
TI  - Endocrine function is not impaired in patients with a continuous MicroMed-DeBakey
      axial flow pump.
AB  - OBJECTIVES: Pulsatile blood flow has been regarded to be of importance for the
      regulation of endocrine organs. A new generation of continuous flow mechanical
      blood pumps is now available for clinical application. Patients with implanted
      MicroMed-DeBakey axial pumps show nonphysiologic low-pulsatile blood flow
      profiles, and therefore it appeared to be of interest to evaluate their possible
      effect on the endocrine system. METHODS: Eight male patients and 1 female
      patients (mean age, 51 +/- 10 years) with end-stage left-sided heart failure were
      implanted with a MicroMed-DeBakey axial pump. After a mean period of 67 +/- 19
      days, basal pituitary hormone concentrations and their responses to a bolus
      injection of hypothalamic releasing hormones were tested. In addition, thyroid
      hormones, testosterone, and plasma and urinary catecholamine levels were measured
      at baseline. RESULTS: Administration of the hypothalamic releasing hormones
      revealed normal responses of all pituitary hormones (adrenocorticotropic hormone,
      thyroid-stimulating hormone, luteinizing hormone, and prolactin), except for
      growth hormone, the response of which was slightly impaired (10.2 +/- 6.8 vs 19.9
      +/- 6.5 ng/L, P < .05). Also, the cortisol response to the corticotropin
      releasing hormone-stimulated adrenocorticotropic hormone release was normal, as
      were basal concentrations of thyroid hormones (triiodothyronine, thyroxine, free
      triiodothyronine, and free thyroxine), testosterone, and urinary catecholamines.
      CONCLUSIONS: Implantation of a continuous flow axial pump with low-pulsatile
      blood flow profile appears to have no major effect on the hypothalamic-pituitary
      endorgan system and sympathoadrenal functions. This finding is reassuring for the
      growing number of patients treated with this convenient new pump and could
      contribute considerably to their prognosis and quality of life.

PMID- 17198774
TI  - Effect of intravenous N-acetylcysteine on outcomes after coronary artery bypass
      surgery: a randomized, double-blind, placebo-controlled clinical trial.
AB  - OBJECTIVE: N-acetylcysteine, a potent anti-inflammatory and antioxidant agent, is
      known to decrease the production of reactive oxygen species after cardiac
      surgery. The objective of this study was to evaluate the effects of intravenous N
      acetylcysteine on clinical and biochemical outcomes after coronary artery bypass
      surgery with cardiopulmonary bypass. METHODS: One hundred patients (mean age 60.5
      years, range 43-78 years, 89% male) undergoing coronary artery bypass grafting at
      the Montreal Heart Institute were randomized to receive either N-acetylcysteine
      (600 mg orally the day before and the morning of the operation, a bolus of 150
      mg/kg of intravenous N-acetylcysteine before skin incision, followed by perfusion
      at 12.5 mg x kg(-1) x h(-1) over 24 hours; n = 50) or placebo (n = 50). The
      patients and clinical team were blinded to group assignments. Preoperative
      characteristics were similar between the two groups. Postoperative clinical data
      (death, myocardial infarction, low-output syndromes, arrhythmias, bleeding,
      transfusion requirements, and intensive care unit and hospital lengths of stay)
      and biochemical markers (creatine kinase MB, troponin T, creatinine, hemoglobin,
      and platelet levels) were evaluated serially over 4 days. RESULTS: Clinical
      outcomes were not significantly different between the two groups with regard to
      the incidence of death, myocardial infarction, bleeding, transfusion
      requirements, intubation time, and hospital length of stay. No differences were
      found in postoperative biochemical markers (troponin T, creatine kinase MB,
      creatinine, hemoglobin, and platelets) between the groups. No differences were
      observed between the groups in interleukin-6 production (P = not significant).
      CONCLUSIONS: Prophylactic use of N-acetylcysteine in patients undergoing coronary
      artery bypass grafting with cardiopulmonary bypass does not lead to improvement
      in clinical results or biochemical markers. Further strategies to decrease
      reperfusion injury should be devised.

PMID- 17198775
TI  - Increased cerebral and renal endothelial nitric oxide synthase gene expression
      after cardiopulmonary bypass in the rat.
AB  - OBJECTIVE: Hemodilution and endothelial nitric oxide synthase genetic
      polymorphism may contribute to cerebral and renal injury after cardiopulmonary
      bypass. This study tested the hypothesis that cardiopulmonary bypass and anemia
      stimulate an increase in cerebral and renal endothelial nitric oxide synthase
      gene expression in an experimental model of cardiopulmonary bypass. METHODS:
      Anesthetized rats underwent a sham procedure without cardiopulmonary bypass
      (sham, n = 5), normothermic bypass for 1 hour (CPB, n = 7), or bypass plus
      hemodilutional anemia (CPB anemia, n = 9). After 24 hours of recovery, RNA was
      extracted from the cerebral cortex, renal cortex, and renal medulla. Quantitative
      reverse transcriptase polymerase chain reaction was used to assess endothelial
      nitric oxide synthase messenger RNA levels in brain and kidney tissues. RESULTS:
      The hemoglobin concentration of anemic CPB rats was significantly lower than that
      of nonanemic rats on bypass (64 +/- 5 vs 99 +/- 8 g x L(-1), P < .001). Cerebral
      cortical endothelial nitric oxide synthase messenger RNA levels were increased
      after cardiopulmonary bypass relative to those of the sham group (11.2 +/- 4.2 vs
      6.3 +/- 1.5 fg, P = .031), without a further increase in anemic rats. Renal
      medullary endothelial nitric oxide synthase messenger RNA levels were
      significantly higher in the CPB anemia group than in the sham and CPB groups (7.1
      +/- 4.4 fg vs 1.8 +/- 0.4 fg vs 3.0 +/- 0.6 fg, P < .001). Renal cortical
      endothelial nitric oxide synthase messenger RNA levels did not change
      significantly. CONCLUSIONS: Normothermic cardiopulmonary bypass was associated
      with higher endothelial nitric oxide synthase messenger RNA levels in kidney and
      brain than was the sham procedure 24 hours after cardiopulmonary bypass. Anemia
      accentuated the increase in renal medullary, but not cerebral cortical,
      endothelial nitric oxide synthase expression. These data provide an approach for
      exploring potential mechanisms by which endothelial nitric oxide synthase may
      contribute to renal and cerebral dysfunction after cardiopulmonary bypass and
      anemia.

PMID- 17198776
TI  - Hemodynamic effects of partial ventricular support in chronic heart failure:
      results of simulation validated with in vivo data.
AB  - OBJECTIVE: Current left ventricular assist devices are designed to provide full
      hemodynamic support for patients with end-stage failing hearts, but their use has
      been limited by operative risks, low reliability, and device-related morbidity.
      Such concerns have resulted in minimum use of left ventricular assist devices for
      destination therapy. We hypothesize that partial circulatory support, which could
      be achieved with small pumps implanted with less-invasive procedures, might
      expand the role of circulatory support devices for treatment of heart failure.
      METHODS: We examine the hemodynamic effects of partial left ventricular support
      using a previously described computational model of the cardiovascular system.
      Results from simulations were validated by comparison with an in vivo hemodynamic
      study. RESULTS: Simulations demonstrated that partial support (2-3 L/min)
      increased total cardiac output (left ventricular assist device output plus native
      heart output) by more than 1 L/min and decreased left ventricular end-diastolic
      pressure by 7 to 10 mm Hg with moderate-to-severe heart failure. Analyses showed
      that the hemodynamic benefits of increased cardiac output and decreased left
      ventricular end-diastolic pressure are greater in less-dilated and less
      dysfunctional hearts. Both the relationships between ventricular assist device
      flow and cardiac output and ventricular assist device flow and left atrial
      pressure predicted by the model closely approximated the same relationships
      obtained during hemodynamic study in a bovine heart failure model. CONCLUSIONS:
      Results suggest that a pump with a flow rate of 2 to 3 L/min could meaningfully
      affect cardiac output and blood pressure in patients with advanced compensated
      heart failure. The development of small devices capable of high reliability and
      minimal complications that can be implanted with less-invasive techniques is
      supported by these findings.

PMID- 17198777
TI  - Hemodilutional anemia impairs neurologic outcome after cardiopulmonary bypass in
      a piglet model.
AB  - OBJECTIVES: The effect of hemodilution on neurologic outcome after
      cardiopulmonary bypass remains unclear. We studied the influences of hematocrit
      on cerebral oxygenation and neuropathologic outcome in a piglet model. METHODS:
      Eleven piglets (9.3 +/- 1.1 kg) were randomized into 2 groups. Five piglets
      (group H) received a total blood prime resulting in a high hematocrit (33.0% +/-
      2.3%), and 6 piglets (group L) received a crystalloid prime resulting in a low
      hematocrit (14.0% +/- 3.2%). Both groups underwent 90 minutes of moderate
      hypothermic cardiopulmonary bypass (28 degrees C) with alpha-stat strategy.
      Cerebral oxygenation was monitored by near-infrared spectroscopy. Group L
      received a blood transfusion immediately after cardiopulmonary bypass to reach
      the postoperative target hematocrit of 30%. The brain was fixed in situ 6 hours
      after weaning from cardiopulmonary bypass, and a histologic score for neurologic
      injury was assessed. RESULTS: There were no significant differences in arterial
      blood gas analyses throughout the experiment between the groups. Mean arterial
      pressure, mixed venous oxygen saturation, and heart rate were significantly
      higher in group H compared with group L during hypothermia. Oxyhemoglobin and
      total hemoglobin signals detected by near-infrared spectroscopy were
      significantly lower in group L (analysis of variance, P < .0001), although the
      tissue oxygenation index was not different during cardiopulmonary bypass. Group L
      showed a poorer histologic score compared with group H (P = .0071). CONCLUSIONS:
      Excessive hemodilution, such as a hematocrit of less than 15%, may be associated
      with a high incidence of neurologic injury. Further studies are required to
      determine the safety limits of hematocrit during pediatric cardiopulmonary
      bypass.

PMID- 17198778
TI  - Roles of cyclooxygenase-2 and phosphorylated Akt (Thr308) in cardiac hypertrophy
      regression mediated by left-ventricular unloading.
AB  - OBJECTIVES: Cyclooxygenase-2 is associated with cardiac hypertrophy during
      chronic heart failure and is regulated through the PI3K/Akt pathway.
      Cyclooxygenase-2-induced cell growth through Akt phosphorylation was demonstrated
      in vitro. In chronic heart failure, left ventricular assist devices lead to
      hypertrophy regression and molecular changes. Therefore, the expression of
      cyclooxygenase-2, phosphorylated Akt (p-Akt), and p-Erk 1/2, as well as cardiac
      hypertrophy before and after left ventricular assist device insertion, was
      investigated. METHODS: In myocardial tissue before and after left ventricular
      assist device insertion, the expression of cyclooxygenase-2, p-Akt (Thr308), p
      Akt (Ser473), and p-Erk 1/2 was demonstrated by immunohistochemistry and
      quantified by morphometry. Colocalization of cyclooxygenase-2 and p-Akt (Thr308)
      was investigated by immuno-doublestaining. RESULTS: A significant decrease of
      cyclooxygenase-2, p-Akt (Thr308), p-Akt (Ser473), and p-Erk 1/2 protein
      expression and hypertrophy regression was observed after left ventricular assist
      device insertion. A significant correlation between cyclooxygenase-2 and p-Akt
      (Thr308) expression, as well as between cyclooxygenase-2 expression and
      cardiomyocyte diameter, was observed before, but not after, left ventricular
      assist device insertion. Only cyclooxygenase-2-positive cardiomyocytes showed
      significant hypertrophy regression on unloading. Sarcoplasmic colocalization of
      cyclooxygenase-2 and p-Akt (Thr308) is present before left ventricular assist
      device insertion and is decreased after unloading, whereas the normal myocardium
      is completely devoid of it. CONCLUSIONS: Left ventricular assist device treatment
      is associated with a significant decrease of cyclooxygenase-2, p-Akt (Thr308), p
      Akt (Ser473), and p-Erk 1/2, and cardiac hypertrophy regression of cyclooxygenase
      2-positive cardiomyocytes. The significant correlation and colocalization in
      cardiomyocytes of cyclooxygenase-2 and p-Akt (Thr308) before left ventricular
      assist device insertion suggests a cross-talk between the 2 molecules in the
      progression of cardiac hypertrophy, which is reversibly regulated by the left
      ventricular assist device.

PMID- 17198779
TI  - Activation of protein C and hemodynamic recovery after coronary artery bypass
      surgery.
AB  - OBJECTIVES: Activated protein C is a physiologic anticoagulant that is activated
      by thrombin and upregulated during coronary artery bypass grafting. We studied
      the balance between thrombin generation and activated protein C levels during
      coronary artery bypass grafting and hypothesized that protein C activation during
      reperfusion is associated with hemodynamic recovery or postoperative myocardial
      damage. METHODS: One hundred patients undergoing elective on-pump coronary artery
      bypass grafting were prospectively studied. Activated protein C, protein C,
      prothrombin fragment F1+2 (a marker of thrombin generation), and D-dimer (a
      marker of fibrinolysis) levels were measured preoperatively and at 7 time points
      during cardiopulmonary bypass and reperfusion and postoperatively. Hemodynamic
      parameters were measured serially. Cardiac biomarkers (mass of the Mb fraction of
      creatine kinase and troponin T) were measured postoperatively. RESULTS:
      Reperfusion induced a significant increase in thrombin generation. Activated
      protein C levels peaked after heparin neutralization, when they increased more
      than 3-fold. Activated protein C levels correlated with F1+2 and D-dimer levels
      during cardiopulmonary bypass and reperfusion. Even though this correlation
      peaked during early reperfusion (r = 0.55, P < .001), the ratio of activated
      protein C to F1+2 decreased during surgical intervention and early reperfusion by
      70% from the preoperative level, indicating a marked delay in protein C
      activation in relation to thrombin generation. Patients in the highest quintile
      of activated protein C levels during this period had a higher postoperative
      cardiac index (mean, 3.1 vs 2.5 L x min(-1) x m(-2); P < .05) and lower systemic
      vascular resistance (mean, 2137 vs 2429 dyne x s x cm(-5) x m(-2); P < .05).
      Conversely, levels of preoperative activated protein C and activated protein C
      measured after heparin neutralization were associated with unfavorable
      hemodynamic recovery postoperatively. Activated protein C or protein C levels
      were not associated with increased postoperative cardiac biomarkers. CONCLUSIONS:
      Reperfusion caused significant thrombin generation that was followed by
      activation of protein C. The balance of activated protein C with thrombin is
      associated dynamically with postoperative hemodynamic recovery.

PMID- 17198780
TI  - Progressive improvement of myocardial perfusion after off-pump revascularization
      with bilateral internal thoracic arteries: comparison of early versus 1-year
      postoperative myocardial single photon emission computed tomography.
AB  - OBJECTIVE: We evaluated the time course of myocardial perfusion improvement after
      off-pump revascularization. METHODS: Seventy-six patients who underwent off-pump
      coronary bypass with bilateral internal thoracic arteries for revascularization
      of the left coronary territory were studied. Myocardial single photon emission
      computed tomography was performed preoperatively and at 3 months and 1 year
      postoperatively. Myocardial perfusion was quantified with automatic software, and
      the left coronary territory was divided into 16 segments. As an indicator of the
      ischemic myocardium, the reversibility score was defined as a measure of rest
      minus stress perfusion values. A total of 403 segments that showed a
      reversibility score of 7 or greater preoperatively were included. RESULTS: The
      reversibility score was improved significantly at 3 months postoperatively (P <
      .001) and further improved 1 year after the operation (P < .001). When the
      patients were divided into 2 groups based on the type of bilateral internal
      thoracic arteries used (group Y: Y-composite graft, n = 39; group I: bilateral in
      situ grafts, n = 37), the reversibility score was improved significantly 3 months
      after the operation (P < .001) and further improved 1 year after the operation (P
      < .001) in both groups. There were no significant differences in the
      reversibility scores between groups Y and I at postoperative month 3 (P = .463).
      The scores approached zero in both groups at 1 year postoperatively (group Y, 
      1.7% +/- 7.9%; group I, 1.3% +/- 7.2%). CONCLUSIONS: The myocardial reversibility
      score improved greatly during the first 3 months after the operation and further
      improved until 1 year postoperatively. Perfusion improvement was similar between
      the Y-composite and bilateral in situ internal thoracic artery grafts in terms of
      the reversibility score.

PMID- 17198781
TI  - Reverse right ventricular remodeling after pulmonary endarterectomy in patients
      with chronic thromboembolic pulmonary hypertension: utility of magnetic resonance
      imaging to demonstrate restoration of the right ventricle.
AB  - OBJECTIVES: Pulmonary arterial hypertension causes right ventricular remodeling;
      that is, right ventricular dilatation, hypertrophy, and leftward ventricular
      septal bowing. We studied the effect of pulmonary endarterectomy on the
      restoration of right ventricular remodeling in patients with chronic
      thromboembolic pulmonary hypertension by magnetic resonance imaging. METHODS: In
      17 patients with chronic thromboembolic pulmonary hypertension, before and at
      least 4 months after pulmonary endarterectomy, and in 12 healthy controls, right
      ventricular and left ventricular end-diastolic and end-systolic volumes
      (milliliters) and mass (grams per meter squared) and leftward ventricular septal
      bowing (1 divided by the radius of curvature in centimeters) were determined by
      magnetic resonance imaging. RESULTS: Before pulmonary endarterectomy, right
      ventricular volumes, left ventricular end-diastolic volume, right ventricular
      mass, and leftward ventricular septal bowing differed significantly between
      patients with chronic thromboembolic pulmonary hypertension and healthy control
      subjects. After pulmonary endarterectomy, pulmonary hemodynamics improved, and
      right and left ventricular volumes and leftward ventricular septal bowing
      normalized; right ventricular mass decreased significantly (46 +/- 14 to 31 +/- 9
      g x m(-2), P< .0005), but did not completely normalize. The change in total
      pulmonary resistance correlated with the change in right ventricular ejection
      fraction (r = 0.50, P < .05), right ventricular mass (r = 0.63, P < .01), and
      leftward ventricular septal bowing (r = 0.50, P < .05). CONCLUSIONS: Right
      ventricular remodeling was observed in patients with chronic thromboembolic
      pulmonary hypertension and restored almost completely after a hemodynamically
      successful pulmonary endarterectomy. Magnetic resonance imaging is a valuable
      tool to evaluate cardiac remodeling and function in patients with chronic
      thromboembolic pulmonary hypertension, both before and after pulmonary
      endarterectomy.

PMID- 17198782
TI  - A multicenter trial of an intrabronchial valve for treatment of severe emphysema.
AB  - OBJECTIVES: Minimally invasive endoscopic treatment of emphysema could provide
      palliation with less risk than lung volume reduction surgery and offer therapy to
      patients currently not considered for lung volume reduction surgery. The
      Intrabronchial Valve is used to block bronchial airflow in the most emphysematous
      areas of lung. METHODS: Patients with severe chronic obstructive pulmonary
      disease and heterogeneous upper lobe-predominant emphysema were eligible.
      Patients underwent flexible bronchoscopic placement of valves into segmental or
      subsegmental airways in both upper lobes. Outcomes assessed over a minimum of 6
      months of follow-up included the safety, feasibility, tolerance, and success of
      valve placement; health-related quality of life; exercise capacity; pulmonary
      function; and gas exchange. RESULTS: Five centers treated 30 patients. Patient
      follow-up ranged from 1 to 12 months. A mean of 6.1 valves were placed per
      patient. Valves were positioned by means of flexible bronchoscopy in 99% of
      desired airways, and the procedure duration ranged from 15 to 125 minutes (mean,
      65 minutes). Hospital discharge occurred within 2 days in 27 of 30 patients.
      There were no deaths or episodes of valve migration, tissue erosion, or
      significant bleeding. Eighty-three percent of patients had no adverse events
      judged probably or definitely related to the device. Patients experienced
      significant improvement in health-related quality of life, although the
      physiologic and exercise outcomes did not show statistically significant
      improvements. CONCLUSIONS: These first multicenter results with the
      Intrabronchial Valve demonstrate significant improvements in health-related
      quality of life and acceptable safety, ease of use, and procedural complication
      rates. The valve might be a safer and less-invasive alternative to surgical
      therapy for patients with severe emphysema.

PMID- 17198784
TI  - Selective decrease in the DNA base excision repair pathway in squamous cell
      cancer of the esophagus.
AB  - OBJECTIVES: Oxidative damage can lead to a highly mutagenic 8-oxoguanine lesion,
      which mispairs with adenosine residues, leading to G:C-->T:A transversions. In
      mammalian cells 8-oxoguanine glycosylase initiates the DNA base excision repair
      pathway to repair the 8-oxoguanine lesion. To date, there is no information
      regarding oxidative DNA damage and repair pathways in esophageal cancer.
      Therefore we designed the current study to demonstrate the DNA damage and repair
      pathways in esophageal cancer by expression of 8-oxoguanine glycosylase in reflux
      induced and mutagen (methyl-n-amyl nitrosamine)-induced DNA damage and apoptosis
      in esophageal tumors. METHODS: Gastroduodenal reflux was surgically created in
      male Sprague Dawley rats (n = 120). Half of the animals received methyl-n-amyl
      nitrosamine. Animals not undergoing operations served as control animals (n =
      10). The experiment concluded 30 weeks postoperatively. Immunohistochemistry for
      8-oxoguanine and 8-oxoguanine glycosylase was assessed by 2 independent
      observers. Protein expression was assessed by using the Western blot method.
      RESULTS: There was significantly more DNA damage in both adenocarcinoma (n = 15)
      and squamous cell carcinoma (n = 19), as exemplified by positive 8-oxoguanine
      expression compared with that seen in control animals (P < .05). 8-Oxoguanine
      glycosylase was several folds upregulated in adenocarcinoma (P < .05), but there
      was significantly decreased expression in squamous cell carcinoma (P < .01). The
      apoptosis was assessed as caspase-dependent and caspase-independent pathways, and
      both were active and correlated well with 8-oxoguanine expression. CONCLUSION:
      These results demonstrate the selective decrease in the DNA base excision repair
      pathway in combined reflux and methyl-n-amyl nitrosamine-induced squamous cell
      cancer of the esophagus.

PMID- 17198786
TI  - A novel biomarker for the detection of esophageal adenocarcinoma.
AB  - OBJECTIVES: Proliferating cell nuclear antigen is a component of the DNA
      synthesome and functions in DNA replication and repair. Our group has recently
      identified an acidic isoform of proliferating cell nuclear antigen, cancer
      specific proliferating cell nuclear antigen, that appears to be present only in
      malignant tissue. We sought to determine the presence of cancer-specific
      proliferating cell nuclear antigen in esophageal dysplasias and invasive
      adenocarcinomas to assess its potential utility in discriminating malignancy.
      METHODS: With a polyclonal antibody to cancer-specific proliferating cell nuclear
      antigen, immunohistochemical staining was performed on samples from a total of 30
      patients with Barrett esophagus with varying degrees of dysplasia and 18 patients
      with invasive adenocarcinoma. We also performed cancer-specific proliferating
      cell nuclear antigen immunohistochemical staining on a commercially available
      tissue microarray and on specimens obtained from endoscopic biopsies. As
      controls, immunohistochemical staining for cancer-specific proliferating cell
      nuclear antigen was performed on normal esophageal tissue and immunohistochemical
      staining for proliferating cell nuclear antigen was performed on all specimens
      with a commercially available antibody. RESULTS: Of the Barrett esophagus
      specimen, 14 showed no dysplasia, 8 showed low-grade dysplasia, and 8 showed high
      grade dysplasia. None of these specimens stained positively for cancer-specific
      proliferating cell nuclear antigen. Of the 18 adenocarcinoma specimens, all
      stained positively for cancer-specific proliferating cell nuclear antigen. There
      was no significant cancer-specific proliferating cell nuclear antigen expression
      in normal esophageal tissue, and proliferating cell nuclear antigen expression
      was noted to a high degree in all tissues. CONCLUSIONS: Cancer-specific
      proliferating cell nuclear antigen appears to demonstrate high specificity for
      esophageal adenocarcinoma. This marker therefore may prove useful in
      differentiating invasive cancer from high-grade dysplasia. Cancer-specific
      proliferating cell nuclear antigen also holds future promise as a biomarker for
      esophageal adenocarcinoma.

PMID- 17198788
TI  - Risk-adjusted morbidity and mortality models to compare the performance of two
      units after major lung resections.
AB  - OBJECTIVE: We sought to develop risk-adjusted morbidity and mortality models to
      compare the performance of 2 different thoracic surgery units in patients
      submitted to major lung resections. METHODS: Seven hundred forty-three patients
      (551 male and 192 female patients) who underwent lobectomy (n = 611) or
      pneumonectomy (n = 132) from January 2000 through August 2004 at 2 European
      thoracic units (519 patients in unit A and 224 patients in unit B) were analyzed.
      Risk-adjusted models of 30-day or in-hospital cardiopulmonary morbidity and
      mortality were developed by using stepwise logistic regression analyses and
      validated by means of bootstrap analysis. Preoperative and operative variables
      were initially screened by using univariate analysis. Those with a P value of
      less than .10 were used as independent variables in the regression analyses. The
      regression equations were then used to estimate the risk of outcome, and the
      observed and predicted outcome rates of the 2 units were compared by using the z
      test for comparison of proportions. RESULTS: The following regression models were
      developed. Predicted morbidity: lnR/1-R=-2.4+0.03Xage
      0.02XppoFEV1+0.6Xcardiaccomorbidity (Hosmer-Lemeshow statistic = 6.1 [P = .6], c
      index = 0.65). Predicted mortality: lnR/1-R=-6.97+0.095Xage-0.042XppoFEV1 (Hosmer
      Lemeshow statistic = 2.99 [P = .9], c index = 0.77). The models proved to be
      stable at bootstrap analyses. No differences were noted between observed and
      predicted outcome rates within each unit, despite an apparent unadjusted better
      performance of unit B. CONCLUSIONS: The use of risk-adjusted outcome models
      avoided misleading information derived from the unadjusted analysis of
      performance. Risk modeling is essential for the evaluation of the quality of
      care.

PMID- 17198790
TI  - The murine bronchopulmonary microcirculation in hapten-induced inflammation.
AB  - OBJECTIVE: The clinical observation of central bronchial artery hypertrophy in
      chronic lung inflammation suggests the possibility that the bronchial circulation
      may also participate in adaptive responses in peripheral lung inflammation.
      METHODS: To investigate the potential role of the bronchial microcirculation in
      peripheral lung inflammation, we developed a murine model of lung inflammation
      using the intratracheal instillation of the peptide-hapten trinitrophenol in
      presensitized mice. RESULTS: Clinical parameters indicated a peak inflammatory
      response at 96 hours. Similarly, gross and microscopic evidence of inflammation
      was observed 96 hours after antigen instillation. Using a forced oscillation
      technique to probe peripheral lung mechanics at 96 hours, we detected no change
      in central airway resistance (P > .05), but a significant increase in peripheral
      tissue resistance (P < .05). The structure of the bronchial circulation was
      investigated by microsphere occlusion of the pulmonary circulation and corrosion
      casting of the bronchial circulation. SEM of the bronchial artery casts
      demonstrated (1) the presence of the peripheral bronchial circulation in mice,
      (2) interconnections of the two systems in the distal bronchial arteries and at
      the level of alveolar capillaries, and (3) functional evidence of increased
      bronchial perfusion of alveolar capillaries during mononuclear inflammation.
      CONCLUSION: These results suggest an important adaptive role of the bronchial
      circulation in pulmonary inflammation.

PMID- 17198792
TI  - Improved survival with pulmonary metastasectomy: an analysis of 1720 patients
      with pulmonary metastatic melanoma.
AB  - OBJECTIVES: The outcomes of patients with metastatic melanoma are poor. Although
      prognostic models have been developed to predict the occurrence of pulmonary
      metastasis from cutaneous melanoma, few data exist to define the outcomes of
      these patients once metastasis has occurred. The objective of this study was to
      discriminate predictors of survival for patients with pulmonary metastatic
      melanoma. METHODS: We found 1720 patients with pulmonary metastasis listed in a
      prospective comprehensive cancer center database of 14,057 consecutive patients
      with melanoma (Jan 1, 1970-June 1, 2004). Demographic and histopathologic data,
      time and location of recurrences, number of pulmonary nodules, and subsequent
      therapies were collected. Univariate and multivariate Cox proportional hazards
      models were used to identify predictors of survival for patients with pulmonary
      metastatic melanoma. RESULTS: The median survival was 7.3 months after
      development of pulmonary metastasis. Significant predictors of survival from the
      multivariate model included nodular histologic type (P = .033), disease-free
      interval (P < .001), number of pulmonary metastases (P = .012), presence of
      extrathoracic metastasis (P < .001), and performance of pulmonary metastasectomy
      (P < .001). Interactions were identified between metastasectomy and disease-free
      interval and presence of extrathoracic metastasis. Surgery was associated with a
      survival advantage of 12 months for patients with a disease-free interval longer
      than 5 years (19 vs 7 months, P < .01) and of 10 months for patients without
      extrathoracic metastasis (18 vs 8 months, P < .01). CONCLUSIONS: When all other
      identified risk factors were controlled for mathematically, metastasectomy
      maintained a significant survival advantage for patients with pulmonary
      metastatic melanoma. These data support the role of surgery for a select subset
      of patients with pulmonary metastasis.

PMID- 17198794
TI  - Impact of lymph node metastasis on outcome after extrapleural pneumonectomy for
      malignant pleural mesothelioma.
AB  - OBJECTIVES: Extrapleural pneumonectomy is a therapeutic option for selected
      patients with malignant pleural mesothelioma. The impact of lymph node metastasis
      on the site of recurrence and the role of mediastinoscopy in the selection of
      patients for extrapleural pneumonectomy, however, remain unclear. METHODS: We
      reviewed 50 consecutive patients undergoing extrapleural pneumonectomy for
      malignant pleural mesothelioma in our institution between January 1993 and March
      2005. RESULTS: The median survival was 11 months, with a 3-year survival of 24%.
      Survival was significantly worse for patients with N2 disease than for those with
      no lymph node metastasis (median survival 10 months vs 29 months, respectively, P
      = .005). Patient sex, histologic cell type, stage, and N2 disease, but not
      mediastinoscopy, had significant impacts on survival according to univariate
      analysis. In a multivariate analysis, however, only the presence of N2 disease
      remained a significant predictor of poor outcome. The proportion of patients with
      N2 disease and the long-term survival was similar regardless of whether
      preoperative mediastinoscopy yielded a negative result. The initial site of
      recurrence was determined in 28 patients (locoregional in 10 and distant in 18).
      The presence of N2 disease had no impact on the site of recurrence. Adjuvant
      hemithoracic radiation therapy, however, significantly decreased the risk of
      locoregional recurrence. CONCLUSIONS: The presence of N2 disease negatively
      affects the prognosis of patients with malignant pleural mesothelioma.
      Mediastinoscopy, however, seems to have a limited role in patient selection for
      extrapleural pneumonectomy. Adjuvant hemithoracic radiation therapy but not N2
      disease affects the risk of locoregional recurrence.

PMID- 17198795
TI  - Suture bicuspidization of the tricuspid valve versus ring annuloplasty for repair
      of functional tricuspid regurgitation: midterm results of 237 consecutive
      patients.
AB  - OBJECTIVE: Uncorrected functional tricuspid regurgitation has serious long-term
      morbidity and mortality. We reviewed our experience with tricuspid posterior
      annular bicuspidization versus ring tricuspid annuloplasty for treatment of
      functional tricuspid regurgitation. METHODS: From 1999 to 2003, 237 patients
      underwent tricuspid annuloplasty for functional tricuspid regurgitation as part
      of their cardiac surgical procedure. Bicuspidization was performed in 157
      patients and ring annuloplasty in 80 patients. Preoperatively, 227 (96%) patients
      had moderate or greater tricuspid regurgitation with a median regurgitation of
      3+. Follow-up information was obtained for 234 (99%) patients with a mean follow
      up time of 3 years. Postoperative transthoracic echocardiograms were assessed for
      severity of tricuspid regurgitation. Moderate or greater tricuspid regurgitation
      was considered significant. Survival and development of recurrent tricuspid
      regurgitation were evaluated by Kaplan-Meier analysis. Tricuspid regurgitation
      and risk factors for recurrent regurgitation were identified and analyzed by
      multivariable ordinal longitudinal methods. RESULTS: At 3 years postoperatively,
      tricuspid regurgitation in patients treated by bicuspidization annuloplasty was
      zero to mild in 75%, moderate in 11%, moderate to severe in 6%, and severe in 8%
      of patients. In those undergoing ring annuloplasty, tricuspid regurgitation was
      zero to mild in 69%, moderate in 14%, moderate to severe in 7%, and severe in
      10%. There was no significant difference between the two groups (P = .18). Risk
      factors for recurrent tricuspid regurgitation included higher preoperative
      regurgitation grade, preoperative tricuspid regurgitation without concomitant
      mitral regurgitation, and higher pulmonary artery systolic pressure. CONCLUSIONS:
      Bicuspidization annuloplasty and ring annuloplasty were effective at eliminating
      tricuspid regurgitation at 3 years postoperatively. Bicuspidization annuloplasty
      is a simple, inexpensive option for addressing functional tricuspid
      regurgitation. All patients with moderate-to-severe functional tricuspid
      regurgitation should undergo tricuspid annuloplasty regardless of the technique
      used.

PMID- 17198797
TI  - The fate of the distal aorta after repair of acute type A aortic dissection.
AB  - OBJECTIVES: The residual aorta's behavior after repair of acute type A dissection
      is incompletely understood. We analyzed segmental growth rates, distal
      reoperation, and factors influencing long-term survival. METHODS: One hundred
      seventy-nine consecutive patients (70% male; mean age, 60 years) with acute type
      A dissection underwent aggressive resection of the intimal tear and open distal
      anastomosis (1986-2003). Hospital mortality was 13.4%. Survivors had serial
      computed tomographic scans: digitization yielded distal segmental dimensions.
      Segment-specific average rates of enlargement and factors influencing faster
      growth were analyzed. Distal reoperations and patient survival were examined.
      RESULTS: Eighty-nine (57%) patients had imaging data sufficient for growth rate
      calculations. The median diameters after repair were as follows: aortic arch, 3.6
      cm; descending aorta, 3.7 cm; and abdominal aorta, 3.2 cm. Subsequent growth
      rates were 0.8, 1.0, and 0.8 mm/y, respectively. Initial size of greater than 4
      cm (P = .005) and initial diameter of less than 4 cm with a patent false lumen (P
      = .004) predicted greater growth in the descending aorta, and male sex (P = .05)
      significantly affected growth in the abdominal aorta. No significant factors were
      found for the aortic arch. There were 25 distal aortic reoperations (16
      patients), and risk of reoperation was 16% at 10 years. Risk factors reducing
      long-term survival after repair of acute type A dissection included age (P <
      .0001), new neurological deficit at presentation (P = .04), absence of
      preoperative thrombus in the false lumen of the ascending aorta (P = .03), and a
      patent distal false lumen postoperatively (P = .06) but not distal reoperation.
      CONCLUSIONS: Growth of the distal aorta after repair of acute type A dissection
      is typically slow and linear. Distal reoperation is uncommon, and late risk of
      death is approximately twice that of a healthy population.

PMID- 17198799
TI  - Systolic anterior motion after mitral valve repair: is surgical intervention
      necessary?
AB  - OBJECTIVE: The natural history and management of patients with systolic anterior
      motion after mitral valve repair are uncertain. METHODS: We performed a
      retrospective chart review and survey follow-up of all patients in whom systolic
      anterior motion developed intraoperatively after mitral valve repair. RESULTS:
      From January 1993 to December 2002, mitral valve repair was performed in 2076
      patients, and in 174 cases (8.4%) systolic anterior motion was identified on
      intraoperative echocardiography. These patients form the study group. Initially,
      patients were managed with a combination of beta-blockade, vasoconstriction with
      phenylephrine, and/or intravascular volume expansion. Four patients had revision
      of repair because of persistent systolic anterior motion, and 3 additional
      patients had revision of repair because of mitral regurgitation from other
      causes. The median follow-up of the remaining 167 patients was 5.4 years (range 0
      13.2 years). There were 2 late reoperations, but none were caused by systolic
      anterior motion or left ventricular outflow tract obstruction. Ninety percent of
      patients were in New York Heart Association class I, 7% were in class II, and 3%
      were in class III or IV. Echocardiograms were available for review in 93 patients
      at a median interval of 5.4 years (range 0.2-12.2 years); 13 patients had
      systolic anterior motion, and 4 patients had systolic anterior motion with left
      ventricular outflow tract obstruction. CONCLUSIONS: In this experience, most
      cases of systolic anterior motion resolved with conservative measures including
      beta-blockade, vasoconstriction, and fluid administration. Persistent systolic
      anterior motion with left ventricular outflow tract obstruction was documented in
      2.3% of patients who had early systolic anterior motion, but late reoperation was
      not required. Furthermore, the clinical outcomes of patients with systolic
      anterior motion are comparable to the current norms for mitral valve repair.
      Ninety percent of patients were in New York Heart Association class I, 7% were in
      class II, and 3% were in class III or IV.

PMID- 17198801
TI  - Surgical treatment of active infective endocarditis: a continued challenge.
AB  - OBJECTIVE: This study was undertaken to examine the outcomes of surgery for
      active infective endocarditis in a large cohort of patients. METHODS: Three
      hundred eighty-three consecutive patients underwent surgery for active infective
      endocarditis. The mean age was 51 +/- 16 years, and 64% were men. The infected
      valve was native in 266 patients and prosthetic in 117. Staphylococcus aureus was
      the most common microorganism. Surgery consisted of valve replacement or repair
      in patients with infection limited to the cusps or leaflets of the valve or
      radical resection of seemingly infected paravalvular tissues, and reconstruction
      with patches and valve replacement in patients with abscess (135 patients). The
      mean follow-up was 6.1 +/- 5.2 years. RESULTS: There were 45 (12%) operative and
      88 (23%) late deaths. The operative mortality did not change during the period of
      study. Preoperative shock, prosthetic valve endocarditis, paravalvular abscess,
      and S aureus were independent predictors of operative mortality. Age, shock,
      prosthetic valve endocarditis, left ventricular ejection fraction less than 40%,
      and recurrent endocarditis were independent predictors of death from all causes.
      Survivals at 15 years were 44% +/- 5% overall, 59% +/- 5% for native valve
      endocarditis, and 25% +/- 7% for prosthetic valve endocarditis (P = .001).
      Freedom from recurrent endocarditis at 15 years was 86% +/- 3% for all patients,
      similar to those for native and prosthetic valve endocarditis (P = .39). Freedom
      from reoperation at 15 years was 70% +/- 6% for all patients, similar to those
      for native and prosthetic valve endocarditis (P = .55). CONCLUSIONS: Surgery for
      endocarditis continues to be challenging and associated with high operative
      mortality and morbidity. Age, shock, prosthetic valve endocarditis, impaired
      ventricular function, and recurrent infections adversely affect long-term
      survival.

PMID- 17198803
TI  - Ethnic diversity: South Asian ethnicity is associated with increased coronary
      artery bypass grafting mortality.
AB  - OBJECTIVE: South Asian ethnicity might result in a higher atherosclerotic
      vascular risk compared with white ethnicity. However, the effect of South Asian
      ethnicity on clinical outcomes after cardiac surgery is unknown. Thus, we
      determined whether South Asian ethnicity is a predictor of a poorer outcome after
      coronary artery bypass grafting. METHODS: We examined data from 6177 South Asian
      and white patients who underwent coronary artery bypass grafting at the Toronto
      General Hospital from January 1994 through June 2003 and used propensity score
      matching techniques to analyze 917 patients from each group in more detail.
      Patients were matched for age, sex, body surface area, left ventricular ejection
      fraction, New York Heart Association class, previous cardiac surgery, number of
      diseased vessels, and other factors. Independent predictors of operative
      morbidity and mortality were determined by means of multivariate logistic
      regression. RESULTS: Overall operative mortality was 1.8%. Mortality was higher
      in South Asian patients than in white patients (2.5% vs 1.1%, P = .02).
      Postoperative morbidity (eg, myocardial infarction, sepsis, sternal wound
      infection, postoperative hospital stay, and use of inotropes) also was higher in
      the South Asian group. In addition to the standard independent predictors of
      mortality, South Asian ethnicity was an independent predictor of mortality (odds
      ratio, 3.1; 95% confidence interval, 1.4-6.8). CONCLUSIONS: These data indicate
      that South Asian ethnicity per se is an independent predictor of a poorer outcome
      after coronary artery bypass grafting and suggest that ethnicity is a
      cardiovascular risk factor that should be considered when assessing clinical
      outcomes preoperatively before coronary artery bypass grafting or other
      interventional revascularization procedures.

PMID- 17198804
TI  - Matrix metalloproteinase and tissue inhibitor expression in atherosclerotic and
      nonatherosclerotic thoracic aortic aneurysms.
AB  - OBJECTIVES: The altered expression of matrix metalloproteinases and their
      inhibitors influences the formation of atherosclerotic abdominal aortic
      aneurysms. Their association with thoracic aneurysms is less clear. This study
      describes the expression of metalloproteinases and their inhibitors in
      atherosclerotic and nonatherosclerotic thoracic aneurysms, and compares these
      with age-matched controls. METHODS: Matrix metalloproteinase-2 and 9 activity
      were measured by antibody capture, and tissue inhibitor-1 and 2 levels were
      measured by enzyme-linked immunosorbent assay in 24 patients with atherosclerotic
      aneurysms and in 63 patients with nonatherosclerotic aneurysms. Gene expression
      was assessed with reverse transcriptase polymerase chain reaction. The results
      were compared with 17 controls. RESULTS: Data are in nanograms per milligram of
      protein. Matrix metalloproteinase-2 activity was greater in controls than in the
      atherosclerotic and nonatherosclerotic groups (80 +/- 67 vs 49 +/- 50 and 35 +/-
      44, P = .002). Matrix metalloproteinase-9 activity was greater in the
      atherosclerotic group than in the nonatherosclerotic group and controls (11.7 +/-
      15.7 vs 2.5 +/- 2.2 and 1.7 +/- 1.9, P = .001). Tissue inhibitor-1 and 2 levels
      were greater in controls than in either aneurysm group (tissue inhibitor of
      metalloproteinase-1: 376 +/- 192 vs 234 +/- 233 and 174 +/- 148, P = .003; tissue
      inhibitor of metalloproteinase-2: 143 +/- 74 vs 14 +/- 13 and 27 +/- 43, P <
      .001). Atherosclerotic aneurysms expressed more matrix metalloproteinase mRNA
      than controls. CONCLUSIONS: The metalloproteinase/tissue inhibitor phenotype of
      atherosclerotic thoracic aneurysms is similar to that of abdominal aneurysms. The
      diminished expression of metalloproteinases and tissue inhibitors in
      nonatherosclerotic thoracic aneurysms relative to aged controls may represent a
      loss of smooth muscle cells.

PMID- 17198805
TI  - Reverse right ventricular remodeling after pulmonary endarterectomy.
AB  - OBJECTIVES: We sought to evaluate the capability of the right ventricle to regain
      normal morphology and function after pulmonary endarterectomy, to correlate right
      ventricular reverse remodeling with functional status, and to identify
      independent predictors of clinical failure after surgical intervention. METHODS:
      From December 2000 through August 2003, 45 patients underwent isolated pulmonary
      endarterectomy. Morphology and function of the right ventricle were studied by
      using a combination of right heart catheterization, cardiac magnetic resonance,
      and transthoracic echocardiography. Functional status was evaluated by using New
      York Heart Association class. Full preoperative data were available for 37
      candidates. All patients were evaluated before discharge, at 3 months, and at 1,
      2, and 3 years postoperatively using the same modalities. RESULTS: Immediately
      after surgical intervention, right ventricular cavitary dimensions decreased
      significantly, and tricuspid regurgitation radically improved. Right ventricular
      ejection fraction and functional status improved and right ventricular
      hypertrophy reversed over a longer time period. Higher ventricular dimensions and
      lower ejection fraction of the right ventricle were associated with poorer
      functional status at any time postoperatively. At discharge, pulmonary vascular
      resistance of greater than 509 dyne x sec x cm(-5) and right ventricular ejection
      fraction of 24% or less predicted clinical failure at 12 months' follow-up.
      CONCLUSIONS: After pulmonary endarterectomy, the right ventricle recovers and
      maintains normal architecture and function over time, regardless of the severity
      of preoperative disease. Accurate preoperative evaluation of the hemodynamics and
      anatomy of the thromboembolic lesions are mandatory. If pulmonary endarterectomy
      is not expected to decrease pulmonary vascular resistance to less than 509 dyne x
      sec x cm(-5), indication for surgical intervention needs to be carefully
      evaluated.

PMID- 17198807
TI  - Postoperative stroke after off-pump versus on-pump coronary artery bypass
      surgery.
AB  - OBJECTIVE: The value of off-pump over conventional coronary artery bypass surgery
      in reducing the risk of postoperative stroke is controversial. This issue has
      been evaluated in light of our recent clinical experience. METHODS: Off-pump
      coronary artery bypass surgery was performed in 557 patients, and conventional
      coronary artery bypass surgery was performed in 445 patients. Preoperative stroke
      risk was calculated according to the Northern New England Cardiovascular Disease
      Study Group stroke risk-scoring method. RESULTS: Off-pump coronary artery bypass
      surgery was associated with a lower but not significant rate of postoperative
      stroke in the overall series (1.8% vs 2.5%, P = .45), a difference that slightly
      increased in the highest tertile of the Northern New England Cardiovascular
      Disease Study Group score (2.8% vs 4.2%, P = .75). The postoperative stroke rate
      was significantly lower when the operation was performed by off-pump coronary
      artery bypass surgeons using routinely epiaortic ultrasonographic scanning
      compared with conventional coronary artery bypass surgeons not using epiaortic
      ultrasonographic scanning (0.4% vs 3.9%, P = .015). The Northern New England
      Cardiovascular Disease Study Group score (mean, 4.6 +/- 2.1 vs 4.9 +/- 2.2; P =
      .189) was similar in these groups. Logistic regression showed that when adjusted
      for Northern New England Cardiovascular Disease Study Group stroke risk score and
      critical preoperative status, the treatment approach (off-pump coronary artery
      bypass surgery and routine epiaortic ultrasonographic scanning) was an
      independent predictor of postoperative stroke (P = .012; odds ratio, 34.1; 95%
      confidence interval, 2.2-533.7). CONCLUSIONS: The neuroprotective efficacy of off
      pump coronary artery bypass surgery is marginal compared with that of
      conventional coronary artery bypass surgery. A decreased risk of postoperative
      stroke after off-pump coronary artery bypass surgery is expected, mostly in high
      risk patients and when epiaortic ultrasonographic examination is routinely used
      for better planning of operative strategy, aiming to minimize the risk of
      intraoperative embolism.

PMID- 17198808
TI  - Impact of left atrial appendage exclusion on left atrial function.
AB  - OBJECTIVES: We sought to investigate the short-term and midterm effects of left
      atrial appendage exclusion on left atrial function. Left atrial appendage
      exclusion is considered a possible therapeutic option for stroke prevention in
      patients with atrial fibrillation. Favorable outcomes have encouraged widespread
      use of left atrial appendage exclusion for cardiac surgical patients-even for
      patients in sinus rhythm who have stroke risk factors; however, the chronic
      effects on left atrial function of left atrial appendage exclusion are unclear.
      METHODS: Nineteen mongrel dogs (29.7 +/- 5.2 kg) in sinus rhythm were studied.
      The Doppler signals from the pulmonary venous flow, transmitral flow, and tissue
      Doppler imaging of mitral annular motion were obtained before and after left
      atrial appendage exclusion. Dogs were evaluated in the same manner at 7 days (n =
      2), 30 days (n = 7), or 90 days (n = 10) after left atrial appendage exclusion.
      RESULTS: Except for a significant increase in early diastolic transmitral flow
      velocity after left atrial appendage exclusion (P = .01), no significant
      differences were found in any parameters related to the transmitral flow and
      tissue Doppler imaging measurements throughout follow-up. The systolic components
      of pulmonary venous flow at follow-up revealed a significant reduction relative
      to baseline (peak systolic velocity P < .0001, systolic velocity-time integral P
      < .0001), despite the lack of significant changes in left atrial pressure, left
      ventricular volume, and stroke volume. CONCLUSION: Left atrial appendage
      exclusion may affect left atrial reservoir function in the short-term and midterm
      periods. Further long-term studies with more clinically relevant models are
      needed.

PMID- 17198809
TI  - Does preoperative atrial fibrillation influence early and late outcomes of
      coronary artery bypass grafting?
AB  - OBJECTIVE: The study objective was to describe the independent effect of
      preoperative atrial fibrillation on the outcome of coronary artery bypass
      grafting, including the causes of death (cardiac vs noncardiac). METHODS: We
      analyzed the outcome of patients with preoperative atrial fibrillation who
      underwent on-pump coronary artery bypass grafting between 1993 and 2002 and
      compared them with matched controls in sinus rhythm; matching variables were age,
      gender, ejection fraction, and numbers of diseased coronary arteries and distal
      anastomoses. Direct patient follow-up focused on late complications and
      reinterventions, and we investigated causes for all deaths. RESULTS: Operative
      mortality (1.6% vs 1.9%, P = .79) was similar in patients with preoperative
      atrial fibrillation (n = 257) compared with patients in sinus rhythm (n = 269).
      The patients with atrial fibrillation had longer hospital stays (9 +/- 6 days vs
      8 +/- 6 days, P = .0008) and a trend to more frequent early readmissions (13% vs
      9%, P = .08). During follow-up (median 6.7 years, maximum 12 years), late
      hospital admission was more frequent in patients with atrial fibrillation (59% vs
      31%, P < .0001). Risk of late mortality (all causes) in patients with atrial
      fibrillation was increased by 40% compared with patients in sinus rhythm (P =
      0.02), and the late cardiac death rate in the atrial fibrillation group was 2.8
      times that of the sinus rhythm group (P = .0004). Major adverse cardiac events
      occurred in 70% of patients with preoperative atrial fibrillation compared with
      52% of patients in preoperative sinus rhythm (P < .0001). Subsequent rhythm
      related intervention, including pacemaker implantations, was more common in the
      atrial fibrillation group (relative risk = 2.1, P = .0027). CONCLUSIONS:
      Uncorrected preoperative atrial fibrillation in patients undergoing coronary
      artery bypass grafting is associated with increased late cardiac morbidity and
      mortality and poor long-term survival. These data support consideration of atrial
      fibrillation surgery at the time of coronary artery bypass grafting.

PMID- 17198810
TI  - Pulmonary homograft muscle reduction to reduce the risk of homograft stenosis in
      the Ross procedure.
AB  - OBJECTIVE: The Ross procedure has gained increasing interest as an attractive
      alternative for aortic valve replacement. Despite its advantages, there is a
      certain risk of structural valve deterioration, especially of the pulmonary
      homograft as a result of shrinkage and subsequent stenosis predominantly at the
      muscular annulus. Theoretically, reduction of homograft muscle tissue could
      reduce this risk. METHODS: From February 1996 through December 2002, a total of
      238 patients (mean age 44 +/- 13.2 years) underwent the Ross procedure with the
      subcoronary technique with follow-up investigations before discharge and after 12
      and 24 months. To estimate the importance of homograft muscle reduction within
      our institution-specific risk factor scale for change of transhomograft pressure
      gradient with time, we performed a generalized estimating equation approach,
      which identified homograft muscle reduction, higher body surface area in male
      patients, younger patient age, smaller homograft diameter, blood transfusions,
      and follow-up time as independent risk factors demonstrating a high beta value (
      2.8638) for muscle reduction. To find out whether muscle reduction influences
      transhomograft pressure gradient, we compared patients with (group A, n = 39) and
      without (group B, n = 199) muscle reduction. The other mentioned independent risk
      factors were not different between groups, except for blood transfusions (group A
      greater than B, P < .01), indicating a negative bias for group A. RESULTS: The
      maximum pressure gradient across the homograft was lower in patients with muscle
      reduction before discharge (4.5 +/- 2.8 mm Hg group A vs 6.2 +/- 3.8 mm Hg group
      B, P = .004) and after 1 (9.3 +/- 5.8 vs 13.1 +/- 8.4 mm Hg, P = .028) and 2
      years (10.8 +/- 7.6 vs 13.7 +/- 7.5 mm Hg, P = .013). No significant differences
      were found concerning homograft insufficiency. CONCLUSIONS: We provide some
      evidence that transhomograft pressure gradient can be reduced significantly
      within the first 2 years after operation by homograft muscle reduction. Longer
      term follow-up is necessary to evaluate this promising operative technique
      further.

PMID- 17198811
TI  - Geometry of the left ventricular outflow tract in fixed subaortic stenosis and
      intact ventricular septum: an echocardiographic study in children and adults.
AB  - OBJECTIVE: We compared the echocardiographic geometry of the preoperative and
      postoperative left ventricular outflow tract in children and adults with isolated
      fixed subaortic stenosis with age- and weight-matched controls to elucidate
      whether the geometry can be modified when surgical intervention is performed at a
      younger age. METHODS: The mitral-aortic valve distance, aortic valve diameter,
      aorto-left ventricular septal angle, degree of aortic valve dextroposition,
      aortic valve-subaortic stenosis distance, width of left ventricular outflow
      tract, left ventricle wall thickness, and septal thickness were determined
      preoperatively and postoperatively in 21 patients and 21 controls. The
      measurements were indexed to body surface area. Patients were divided into 3 age
      groups: group 1 comprised 9 patients aged 1 to 10 years, group 2 comprised 8
      patients aged 11 to 20 years, and group 3 comprised 4 patients aged 21 years or
      more. RESULTS: Compared with controls, patients had a significantly wider mitral
      aortic separation (group 1, P = .003; group 2, P = .02), a steeper aortoseptal
      angle (group 1, P = .02; group 3, P = .03), a smaller left ventricular outflow
      tract width (group 1, P = .003; group 2, P = .01), a marked aortic valve
      dextroposition (groups 1 and 3), an increased left ventricle wall thickness
      (group 1, P = .03), and an increased septal thickness (group 1, P = .01). There
      was a significant difference between preoperative and postoperative values in
      aortoseptal angle and left ventricular outflow tract width in patients up to 10
      years of age (P = .02 and P = .01, respectively). CONCLUSIONS: Hearts with
      isolated subaortic stenosis have abnormal left ventricular outflow tract geometry
      that postoperatively showed changes in left ventricular outflow tract width and
      aortoseptal angle. Compared with controls, the aortoseptal angle does not
      "normalize" when surgery is performed in older patients, suggesting that left
      ventricular outflow tract geometry may be remodeled in younger patients.

PMID- 17198812
TI  - Initial United States experience with the Paracor HeartNet myocardial constraint
      device for heart failure.
AB  - OBJECTIVE: This study was undertaken to review the initial results and surgical
      safety data for the US Food and Drug Administration safety and feasibility trial
      of the Paracor HeartNet (Paracor Medical, Inc, Sunnyvale, Calif.) myocardial
      constraint device. METHODS: Patients with New York Heart Association functional
      class II or III heart failure underwent device implantation (n = 21) through a
      left minithoracotomy. RESULTS: The average age was 53 years (31-72 years). There
      were 18 men and 3 women, and 17 patients had nonischemic etiology of heart
      failure. Mean heart failure duration was 8.3 years (1.4-18.8 years). Average
      ejection fraction was 22% (11%-33%), with an average left ventricular end
      diastolic dimension of 74 mm (55-94 mm). Previous medical therapy included
      angiotensin-converting enzyme inhibitors, beta-blockers, diuretics, digoxin, and
      aldosterone receptor blockers. At implantation, 17 patients had implantable
      electronic devices: 1 biventricular pacemaker, 11 biventricular pacemakers with
      cardioverter-defibrillators, and 5 implantable cardioverter-defibrillators.
      Patient comorbidities included hypertension in 10 cases, diabetes mellitus in 8,
      myocardial infarction in 1, and ventricular tachycardia in 8. Mean operative time
      was 68 minutes (42-102 minutes), and implantation time averaged 15 minutes (5-51
      minutes). The average time to ambulation was 1.6 days (1-4 days). The intensive
      care unit stay averaged 3.3 days (1-16 days), and hospital stay averaged 6.3 days
      (4-16 days). Atrial fibrillation occurred in 2 patients, and there were 2 in
      hospital deaths. CONCLUSIONS: The Paracor device can be implanted in patients
      with heart failure and reduced left ventricular function with a high degree of
      success. Significant surgical complications were infrequent. The initial US
      experience supports the conduct of a randomized, controlled, pivotal trial.

PMID- 17198814
TI  - Proteomics in cardiovascular surgery.
AB  - Proteomics describes, analogous to the term genomics, the study of the complete
      set of proteins present in a cell, organ, or organism at a given time. The genome
      tells us what could theoretically happen, whereas the proteome tells us what does
      happen. Therefore, a genomic-centered view of biologic processes is incomplete
      and does not describe what happens at the protein level. Proteomics is a
      relatively new methodology and is rapidly changing because of extensive advances
      in the underlying techniques. The core technologies of proteomics are 2
      dimensional gel electrophoresis, liquid chromatography, and mass spectrometry.
      Proteomic approaches might help to close the gap between traditional
      pathophysiologic and more recent genomic studies, assisting our basic
      understanding of cardiovascular disease. The application of proteomics in
      cardiovascular medicine holds great promise. The analysis of tissue and
      plasma/serum specimens has the potential to provide unique information on the
      patient. Proteomics might therefore influence daily clinical practice, providing
      tools for diagnosis, defining the disease state, assessing of individual risk
      profiles, examining and/or screening of healthy relatives of patients, monitoring
      the course of the disease, determining the outcome, and setting up individual
      therapeutic strategies. Currently available clinical applications of proteomics
      are limited and focus mainly on cardiovascular biomarkers of chronic heart
      failure and myocardial ischemia. Larger clinical studies are required to test
      whether proteomics may have promising applications for clinical medicine.
      Cardiovascular surgeons should be aware of this increasingly pertinent and
      challenging field of science.

PMID- 17198815
TI  - The cone reconstruction of the tricuspid valve in Ebstein's anomaly. The
      operation: early and midterm results.
AB  - OBJECTIVES: We sought to describe a new technique for tricuspid valve repair in
      Ebstein's anomaly and to report early echocardiographic results, as well as early
      and midterm clinical outcomes. METHODS: From November 1993 through August 2005,
      40 consecutive patients with Ebstein's anomaly (mean age, 16.8 +/- 12.3 years)
      underwent a new surgical repair modified from Carpentier's procedure, the
      principal details of which are as follows. The anterior and posterior tricuspid
      valve leaflets are mobilized from their anomalous attachments in the right
      ventricle, and the free edge of this complex is rotated clockwise to be sutured
      to the septal border of the anterior leaflet, thus creating a cone the vertex of
      which remains fixed at the right ventricular apex and the base of which is
      sutured to the true tricuspid valve annulus level. Additionally, the septal
      leaflet is incorporated into the cone wall whenever possible, and the atrial
      septal defect is closed in a valved fashion. RESULTS: There was 1 (2.5%) hospital
      death and 1 late death. Early postoperative echocardiograms have shown good right
      ventricular morphology and reduction in tricuspid regurgitation grade from 3.6 +/
      0.5 to 1.2 +/- 0.5 (P < .0001). After mean follow-up of 4 years, the functional
      class (New York Heart Association) improved from 2.6 +/- 0.7 to 1.2 +/- 0.4 (P <
      .0001). Two patients required late tricuspid valve re-repair, and there was
      neither atrioventricular block nor tricuspid valve replacement at any time.
      CONCLUSIONS: This surgical technique for Ebstein's anomaly can be performed with
      low mortality and morbidity. Early echocardiograms showed significant reduction
      of tricuspid insufficiency, and the follow-up showed improvement in patients'
      clinical status and low incidence of reoperation.

PMID- 17198817
TI  - Cardiac index monitoring by pulse contour analysis and thermodilution after
      pediatric cardiac surgery.
AB  - OBJECTIVES: To validate a new device (PiCCO system; Pulsion Medical Systems,
      Munich, Germany), we compared cardiac index derived from transpulmonary
      thermodilution and from pulse contour analysis in pediatric patients after
      surgery for congenital heart disease. We performed a prospective clinical study
      in a pediatric cardiac intensive care unit of a university hospital. METHODS:
      Twenty-four patients who had had cardiac surgery for congenital heart disease
      (median age 4.2 years, range 1.4-15.2 years) were investigated in the first 24
      hours after admission to the intensive care unit. A 3F thermodilution catheter
      was inserted in the femoral artery. Intracardiac shunts were excluded by
      echocardiography intraoperatively or postoperatively. Cardiac index derived from
      pulse contour analysis was documented in each patient 1, 4, 8, 12, 16, 20, and 24
      hours after admission to the intensive care unit. Subsequently, a set of three
      measurements of thermodilution cardiac indices derived by injections into a
      central venous line was performed and calculated by the PiCCO system. RESULTS:
      The mean bias between cardiac indices derived by thermodilution and those derived
      by pulse contour analysis over all data points was 0.05 (SD 0.4) L x min x m(-2)
      (95% confidence interval 0.01-0.10). A strong correlation between thermodilution
      and contour analysis cardiac indices was calculated (Pearson correlation
      coefficient r = 0.93; coefficient of determination r2 = 0.86). CONCLUSIONS: Pulse
      contour analysis is a suitable method to monitor cardiac index over a wide range
      of indices after surgery for congenital heart disease in pediatric patients.
      Pulse contour analysis allows online monitoring of cardiac index. The PiCCO
      device can be recalibrated with the integrated transpulmonary thermodilution
      within a short time frame.

PMID- 17198818
TI  - Morphologic features of the uniatrial but biventricular atrioventricular
      connection.
AB  - OBJECTIVES: Hearts with an absent atrioventricular connection and a straddling of
      the solitary atrioventricular valve are rare but significant lesions. They are
      suitable only for Fontan-like palliation, in which atrioventricular valvar
      abnormalities play a significant role in determining the outcome. We studied the
      segmental arrangements in such lesions and clarified the valvar morphology,
      particularly its surgical implications. METHODS: We made a macroscopic review of
      all specimens with an absent atrioventricular connection and a straddling
      atrioventricular valve that were held in the collections of 3 institutes. We
      included only those specimens with the straddling valve supported exclusively by
      either the right-sided or left-sided atrioventricular junction and excluded those
      with a common atrioventricular junction. RESULTS: We found 11 hearts with an
      absent right atrioventricular connection and a straddling left atrioventricular
      valve, and 3 with an absent left atrioventricular connection and a straddling
      right atrioventricular valve. Most had right-hand ventricular topology and
      discordant ventriculoarterial connections. We found multiple valvar
      abnormalities, including dysplastic leaflets, short cords, abnormal attachments,
      and abnormal papillary muscles. The most consistent features were a line of
      maximal coaptation between the bridging leaflets always perpendicular to the
      plane of the ventricular septum and a free-floating bridging anterosuperior
      leaflet. CONCLUSIONS: Straddling of a solitary atrioventricular valve with an
      absent atrioventricular connection produces a uniatrial but biventricular
      connection. In this setting, the valve guarding the abnormal solitary
      atrioventricular junction cannot be classified morphologically as mitral or
      tricuspid. The markedly variable valvar morphology likely makes these valves
      prone to insufficiency in the long term.

PMID- 17198819
TI  - Unmeasured anions in children after cardiac surgery.
AB  - OBJECTIVES: Acidosis caused by increased unmeasured anion levels occurs
      frequently after cardiac surgery, with uncertain significance. We examined the
      ability of unmeasured anions and lactate to predict major events after cardiac
      surgery, in addition to lactate/increased unmeasured anion levels during low
      cardiac output states. METHODS: In the initial 6 months, all patients admitted
      after cardiac surgery were enrolled. Arterial samples were taken at 0, 4, 8, 12,
      24, and 36 hours postoperatively. The Stewart method was used to calculate excess
      acid and unmeasured anion levels. Major adverse events were defined as low
      cardiac output states requiring cardiac massage or mechanical support. In the
      second 6-month period, data were collected from a further 8 infants during
      cardiac arrest/extracorporeal membrane oxygenation cannulation. RESULTS: One
      hundred thirteen patients were analyzed. Major adverse events occurred in 8
      (7.1%) of 113 patients. On admission, metabolic acidosis occurred in 94 of 113
      samples: lactate alone (n = 25); mixed lactate and unmeasured anions (n = 44);
      and unmeasured anions alone (n = 25). All of the patients who experienced major
      adverse events had unmeasured anion levels of greater than 3 mEq/L on admission.
      Initial unmeasured anion levels were significantly higher in those infants with
      major adverse events (10.6 mEq/L [standard deviation, 8.2 mEq/L] vs 4.8 mEq/L
      [standard deviation, 6.6 mEq/L], P = .024). Lactate levels did not differ between
      the 2 groups. In the 16 patients sampled during major adverse events, metabolic
      acidosis occurred in 15 of 16, with a mean excess acid level of 14.9 mEq/L
      (standard deviation, 8.3 mEq/L). Although unmeasured anions made a significant
      contribution, lactate was the predominant acid. CONCLUSIONS: After cardiac
      surgery, unmeasured anion levels were significantly higher in those children with
      major adverse events. The greatest risk of major adverse events was found in
      children with both increased lactate levels and increased unmeasured anion levels
      on admission.

PMID- 17198820
TI  - Intermittent warm blood cardioplegia in the surgical treatment of congenital
      heart disease: clinical experience with 1400 cases.
AB  - OBJECTIVE: To analyze our experience with warm blood cardioplegia in pediatric
      cardiac surgery. METHODS: We used intermittent (every 15 minutes after initial
      injection) warm blood cardioplegia in the treatment of 1400 patients. Results
      were retrospectively compared with those of 950 patients treated with cold blood
      cardioplegia. The following parameters were analyzed: (1) hydric balance of
      cardioplegic solution; (2) resumption of rhythm after aortic crossclamp removal;
      (3) duration of mechanical ventilation, intensive care unit stay, and incidence
      of mortality in 4 selected diagnostic groups: ventricular septal defect,
      tetralogy of Fallot, atrioventricular septal defect, and transposition of the
      great arteries. These 4 groups, treated with warm or cold cardioplegia, were
      comparable with regard to age, weight, crossclamp times, and percent with Down
      syndrome; (4) troponin level at 12 hours after aortic crossclamping; and (5)
      duration of intensive care unit stay for the 1400 patients. RESULTS: Warm versus
      cold cardioplegia: negligible fluid addition with warm cardioplegia compared with
      blood loss/prime dilution induced by cold cardioplegia; spontaneous resumption of
      sinus rhythm in 99% versus 77% of patients (P < .001); shorter duration of
      ventilatory support in each diagnostic group, significant in all cases; smaller
      increase in troponin in each group (P < .05). Incidence of early death was not
      different in the 2 groups. For the whole group, duration of the intensive care
      unit stay was less than 48 hours in 86% versus 75% (P < .001). CONCLUSION: In our
      experience, normothermic cardioplegia has not generated any particular
      inconvenience and its use was contemporary, with improved outcomes.

PMID- 17198821
TI  - RING plus STRING: papillary muscle repositioning as an adjunctive repair
      technique for ischemic mitral regurgitation.

PMID- 17198822
TI  - An alternative technique for aortic root remodeling in patients with bicuspid
      aortic valve.

PMID- 17198823
TI  - A rare type of right atrial tumor in a 66-year-old woman.

PMID- 17198824
TI  - Valve-sparing aortic root replacement in a patient with a rare connective tissue
      disorder: arterial tortuosity syndrome.

PMID- 17198825
TI  - Surgical management of symptomatic cardiac fibromas in children.

PMID- 17198826
TI  - An approach to interrupted aortic arch associated with transposition of the great
      arteries.

PMID- 17198827
TI  - Surgical treatment of a rare association: aberrant right coronary origination,
      coronary arteriovenous fistula, and aortic root aneurysm.

PMID- 17198828
TI  - Ascending-descending aortic bypass surgery in aortic arch coarctation: four
      dimensional magnetic resonance flow analysis.

PMID- 17198829
TI  - Endovascular repair of aortic arch aneurysm after achievement of local
      anesthesia.

PMID- 17198830
TI  - Thoracoscopic mediastinal repositioning for postpneumonectomy syndrome.

PMID- 17198831
TI  - Primary pulmonary malignant schwannoma with extension to the tracheal carina.

PMID- 17198832
TI  - Video-assisted mediastinoscopy improved radical resection for cancer in
      transhiatal esophagectomy.

PMID- 17198833
TI  - Major hemorrhage and subsequent cardiac tamponade during mediastinoscopy.

PMID- 17198834
TI  - Descending necrotizing mediastinitis in a child with chickenpox.

PMID- 17198835
TI  - Technique of right single-lung transplantation for idiopathic pulmonary fibrosis
      using cross-field ventilation.

PMID- 17198836
TI  - Surgical damage of the saphenous vein and graft patency.

PMID- 17198837
TI  - Restaging patients with N2 (stage IIIa) non-small cell lung cancer after
      neoadjuvant chemoradiotherapy: a closer look at redo mediastinoscopy.

PMID- 17198839
TI  - Ascending-descending aortic bypass with the aid of a heart-lifting device.

PMID- 17198842
TI  - Pulmonary transfusion reactions.
AB  - Transfusion reactions remain a common complication of transfusion therapy;
      reactions affecting the lungs are some of the most serious. Several different
      mechanisms are responsible for pulmonary transfusion reactions, and most cause
      adverse effects in addition to lung injury. Fluid overload can lead to pulmonary
      edema, antibodies reacting with plasma proteins can cause bronchospasm and
      anaphylaxis, and particulate matter can produce microemboli. These reactions are
      well understood and usually can be prevented. Transfusions are also associated
      with acute lung injury and acute respiratory distress syndrome (ARDS), but their
      etiology is poorly understood and they remain clinically problematic. Neutrophil
      antibodies cause some of these serious as well as mild pulmonary reactions, but
      the exact role of leukocyte antibodies in pulmonary reactions remains unclear.
      Other blood donor, blood component, and transfusion recipient factors likely play
      a contributing or modulating role in pulmonary transfusion reactions, but
      prospective studies are needed to better understand their role.

PMID- 17198843
TI  - Granulocyte transfusion: current status.
AB  - Infection associated with therapy-related neutropenia continues to be a major
      cause of morbidity and mortality. Renewed interest in granulocyte transfusion
      therapy as treatment for this condition has been generated by the observation
      that large doses of granulocytes can be obtained from donors who have been
      stimulated with granulocyte colony-stimulating factor (G-CSF). Granulocytes
      collected from these donors have been shown to effectively raise the patient's
      neutrophil count and appear to function normally as judged both by in vitro and
      in vivo measures. The evidence for clinical efficacy is limited to that of case
      reports and small series, and the results are not uniform. Randomized controlled
      clinical trials are needed to determine whether this therapy is useful in either
      clearing infections or prolonging survival.

PMID- 17198844
TI  - Transfusion-associated microchimerism: a new complication of blood transfusions
      in severely injured patients.
AB  - Microchimerism, the stable persistence of an allogeneic cell population, can
      result from allogeneic exposures including blood transfusion. Transfusion
      associated microchimerism (TA-MC) appears to be a common but newly recognized
      complication of blood transfusion. Thus far TA-MC has been detected when severely
      injured patients are transfused. Injury induces an immunosuppressive and
      inflammatory milieu in which fresh blood products with replication-competent
      leukocytes can sometimes cause TA-MC. TA-MC is present in approximately half of
      transfused severely injured patients at hospital discharge and is not affected by
      leukoreduction. In approximately 10% of patients, the chimerism from a single
      blood donor may increase in magnitude over months to years, reaching as much as
      2% to 5% of all circulating leukocytes. In this review, we discuss recent studies
      of TA-MC in the civilian trauma population and the potential for study of TA-MC
      in the military population, where the severity of injury and freshness of blood
      products suggest that TA-MC may be even more prominent. We also discuss the need
      for future studies to address the immunology of TA-MC, its stem cell biology, and
      its clinical manifestations that have the potential to be either pathologic
      (autoimmunity, graft-versus-host disease) or therapeutic (tolerance induction,
      various cell and gene therapies).

PMID- 17198845
TI  - Emerging infectious diseases that threaten the blood supply.
AB  - Following the devastating effects of blood-transmitted human immunodeficiency
      virus (HIV), blood establishments have become increasingly vigilant for the
      emergence or re-emergence of new threats to the safety of the blood supply. Many
      agents have fulfilled the broad definition of emerging blood-transmitted
      infections, including West Nile virus (WNV), Trypanosoma cruzi, Plasmodium spp.,
      Babesia spp., parvovirus B19, dengue virus, and the prions that cause variant
      Creutzfeld-Jacob disease (vCJD). Other agents such as human herpes virus-8 (HHV-8
      Kaposi's sarcoma virus) and Borellia (Lyme disease) and, perhaps, avian flu
      virus, are known to have a viremic phase, but have not yet been proved to be
      transfusion-transmitted. In the wake of these threats, transfusion services use a
      variety of donor screening interventions, including serologic assays, nucleic
      acid assays, and geographic exclusions based on potential exposure. The ultimate
      safeguard may be a pre-emptive pathogen inactivation strategy that will disrupt
      all nucleic acid-containing agents (though not prions). Considerable effort and
      resources have been invested in this arena, but currently no single technique is
      effective for inactivation of both liquid and cellular blood products and
      toxicity issues have not been completely resolved. The blood supply is remarkably
      safe with the risk of major pathogens such as hepatitis C virus (HCV) and HIV now
      reduced to less than one transmission per 2 to 3 million exposures. However, to
      approach near-zero infectious disease risk for emerging and re-emerging
      pathogens, new strategies such as pathogen inactivation or multi-pathogen
      microarray technology will need to be developed or refined.

PMID- 17198847
TI  - Red cell substitutes.
AB  - Oxygen-carrying plasma expanders (blood substitutes) have been sought for over a
      century. Development of current products is a result of evolution in the
      understanding of proteins in general, of hemoglobin in particular, and of how
      cell-free hemoglobin interacts with the control of local blood flow to ensure
      adequate tissue oxygenation. Hemoglobin-based products are considered in four
      "generations" corresponding to major improvements. First-generation products
      consisted of hemoglobin, freed of red cell membranes (stroma-free hemoglobin
      [SFH]), which was renal toxic and vasoactive. Second-generation products were
      polymerized with aldehyde reagents to reduce or eliminate the renal toxicity, but
      the products were heterogeneous and still vasoactive. Third-generation products
      employed more specific intramolecular crosslinking to eliminate polymerization
      and promote homogeneity, but they also remained vasoactive. Fourth-generation
      products are based on a new understanding of the way in which microvascular blood
      flow is controlled and the influence of O(2) delivery to vascular walls. After
      more than a century of research, one of these new solutions should find use as an
      alternative to red cells for transfusion in certain clinical settings.

PMID- 17198846
TI  - The structure and function of the Rh antigen complex.
AB  - The Rh system is one of the most important and complex blood group systems
      because of the large number of antigens and the serious complications for the
      fetus of a woman sensitized by transfusion or pregnancy. Major advances in our
      understanding of the Rh system have occurred with the cloning of the genes and
      with functional evidence that the Rh blood group proteins belong to an ancient
      family of membrane proteins involved in ammonia transport. The arrangement and
      configuration of the genes at the RH locus promotes genetic exchange, generating
      new antigens. Importantly, RH genetic testing can now be applied to clinical
      transfusion medicine and prenatal practice. This includes testing for RHD
      zygosity, confirmation or resolution of D antigen status, and detection of
      altered RHD and RHCE genes in individuals at risk for producing antibodies to
      high-incidence Rh antigens, particularly sickle cell disease (SCD) patients. The
      Rh proteins form a core complex that is critical to the structure of the
      erythrocyte membrane, and they may play a physiologic role in the sequestration
      of blood ammonia. The Rh family of proteins now includes non-erythroid homologs
      present in many other tissues, and comparative genomics reveal Rh homologs in all
      domains of life.

PMID- 17198848
TI  - Into the looking glass: factors and opportunities to reshape eye care in the next
      25 years.

PMID- 17198849
TI  - Toric Implantable Collamer Lens for moderate to high myopic astigmatism.
AB  - PURPOSE: To assess the efficacy of the Toric Implantable Collamer Lens (ICL) to
      treat moderate to high myopic astigmatism. DESIGN: Prospective nonrandomized
      clinical trial. PARTICIPANTS: Two hundred ten eyes of 124 patients with between
      2.38 and 19.5 diopters (D) of myopia (spherical equivalent [SE]) and 1 to 4 D of
      astigmatism participating in the United States Food and Drug Administration
      clinical trial of the Toric ICL. INTERVENTION: Implantation of the Toric ICL.
      MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), refraction, best
      spectacle-corrected visual acuity (BSCVA), adverse events, and postoperative
      complications. RESULTS: At 12 months postoperatively, the proportion of eyes with
      20/20 or better UCVA (83.1%) was identical to the proportion of eyes with
      preoperative 20/20 or better BSCVA (83.1%); 76.5% had postoperative UCVA better
      than or equal to preoperative BSCVA. The mean manifest refractive cylinder
      dropped from 1.93 D (+/-0.84) at baseline to 0.51 D (+/-0.48) postoperatively, a
      73.6% decrease in astigmatism. Although only 21.0% of eyes had 1-D refractive
      cylinder preoperatively (none less), 91.4% of cases had < or =1 D of cylinder
      postoperatively. Furthermore, 65.6% had < or =0.5 D and 40.9% had < or =0.25 D of
      refractive cylinder postoperatively. Mean manifest refraction SE (MRSE) improved
      from -9.36 D (+/-2.66) preoperatively to 0.05 D (+/-0.46) postoperatively. A
      total of 76.9% of eyes were predicted accurately to within +/-0.5 D, 97.3% to
      within +/-1.0 D, and 100% to within +/-2.0 D of predicted MRSE. Postoperatively,
      37.6% of eyes had a BSCVA of 20/12.5 or better, compared with a preoperative
      level of 4.8%. Furthermore, BSCVA of 20/20 or better occurred in 96.8%
      postoperatively, compared with 83.1% preoperatively. Mean improvement in BSCVA
      was 0.88 lines; there were 3 cases (1.6%) that lost > or =2 lines of BSCVA after
      12 months postoperatively, whereas 18.9% of cases improved by > or =2 lines. A
      total of 76.4% of cases gained > or =1 lines of BSCVA, whereas only 7.5% of cases
      lost the equivalent amount. Three ICL removals were performed without significant
      loss of BSCVA, and 1 clinically significant lens opacity was observed.
      CONCLUSION: The results support the efficacy and predictability of Toric ICL
      implantation to treat moderate to high myopic astigmatism. Important safety
      concerns were not identified.

PMID- 17198850
TI  - In vivo laser confocal microscopy findings for Bowman's layer dystrophies (Thiel
      Behnke and Reis-Bucklers corneal dystrophies).
AB  - OBJECTIVE: To investigate microstructures in patients with genetically confirmed
      Bowman's layer dystrophies (Thiel-Behnke or Reis-Bucklers corneal dystrophy)
      using an in vivo laser scanning confocal microscope. DESIGN: Single-center,
      prospective, comparative small case series. PARTICIPANTS: Two patients from one
      pedigree (a 29-year-old woman and 58-year-old man) with Thiel-Behnke corneal
      dystrophy (Arg555Gln [R555Q] heterozygous missense mutation of human transforming
      growth factor beta-induced [TGFBI] gene) and 3 patients from one pedigree (a 70
      year-old woman, 58-year-old man, and 14-year old man) with Reis-Bucklers corneal
      dystrophy (Arg124Leu [R124L] heterozygous missense mutation of the TGFBI gene)
      were examined. Two patients with Reis-Bucklers corneal dystrophy exhibited
      recurrence after corneal transplantation. TESTING: All patients were examined by
      slit-lamp biomicroscopy. The center and the peripheral cornea of both eyes also
      were examined by in vivo laser scanning confocal microscopey. Image analysis was
      used to identify the corneal epithelial and stromal deposits correlated with each
      disorder. MAIN OUTCOME MEASURES: Selected images of the corneal layers were
      evaluated qualitatively for the shape and degree of light reflection of the
      deposits. RESULTS: In each dystrophy, distinct characteristic deposits were
      observed in the epithelium and Bowman's layer, respectively, by in vivo laser
      scanning confocal microscopy. In Thiel-Behnke corneal dystrophy, the deposits in
      the epithelial basal cell layer showed homogeneous reflectivity with round edges
      accompanying dark shadows. In contrast, deposits in Reis-Bucklers corneal
      dystrophy in the same cell layer showed extremely high reflectivity from small
      granular materials without any shadows in all cases. In each dystrophy, Bowman's
      layer was replaced totally with pathological materials; the reflectivity of those
      materials is much higher in Reis-Bucklers corneal dystrophy than in Thiel-Behnke
      corneal dystrophy. CONCLUSIONS: In vivo laser scanning confocal microscopy is
      capable of identifying in vivo corneal microstructural changes related to Thiel
      Behnke and Reis-Buckler corneal dystrophy with a higher resolution than is
      available with slit-lamp biomicroscopy or in vivo white-light confocal
      microscopy. As a result, this device may enable differentiation of Thiel-Behnke
      and Reis-Bucklers corneal dystrophy in vivo. In vivo laser scanning confocal
      microscopy also may be a valuable tool for further research into the corneal
      dystrophies, especially to follow the natural course.

PMID- 17198851
TI  - Age-related macular degeneration and risk of coronary heart disease: the
      Atherosclerosis Risk in Communities Study.
AB  - OBJECTIVE: To examine the association of age-related macular degeneration (AMD)
      with incident coronary heart disease (CHD) and all-cause mortality. DESIGN:
      Population-based prospective cohort study. PARTICIPANTS: From the Atherosclerosis
      Risk in Communities Study (n = 12 536; age range, 49-73 years). METHODS:
      Participants had retinal photographs of one eye taken between 1993 and 1995.
      Photographs were evaluated for the presence of early and late AMD signs according
      to the Wisconsin grading system. Incident CHD events (acute myocardial
      infarction, silent myocardial infarction, fatal CHD, and cardiac
      revascularization procedures) and all-cause mortality were identified
      prospectively using standardized methods. MAIN OUTCOME MEASURES: Incident CHD
      events and all-cause mortality. RESULTS: Of 11,414 persons at risk of CHD, there
      were 555 (4.9%) with AMD at baseline, of whom 540 were early AMD and 15 were late
      AMD cases. Over a 10-year follow-up, 922 persons developed an incident CHD event.
      After controlling for age, gender, race, systolic and diastolic blood pressure,
      pack-years of cigarette smoking, and other variables, early AMD was not
      associated with incident CHD (relative risk, 1.08; 95% confidence interval, 0.82
      1.42). However, individuals with late AMD were significantly more likely to have
      an incident CHD event, with 4 CHD events among the 15 participants with late AMD
      at baseline (10-year cumulative incidence, 30.9%) as compared with 918 CHD events
      among the 11 399 participants without late AMD (incidence of 10.0%; P = 0.049,
      Fisher exact test). In the full cohort (n = 12 536), early AMD was not
      significantly associated with all-cause mortality. However, individuals with late
      AMD were more likely to die (10-year cumulative mortality rate, 23.5%) than those
      without late AMD (mortality rate, 8.9%; P = 0.088, Fisher exact test).
      CONCLUSIONS: These data provide no evidence of an association between early AMD
      signs with incident CHD and all-cause mortality in middle-aged persons.
      Individuals with late AMD appear to have a higher rate of CHD events than those
      without late AMD, but due to a small number of late AMD cases, this finding
      should be interpreted cautiously.

PMID- 17198852
TI  - Ten-year incidence and progression of age-related maculopathy: the blue Mountains
      Eye Study.
AB  - PURPOSE: To assess the 10-year incidence of age-related maculopathy (ARM) in an
      older Australian cohort. DESIGN: Population-based cohort study. PARTICIPANTS:
      Three thousand six hundred fifty-four Blue Mountains Eye Study participants > or
      =49 years old were examined during 1992 through 1994; 2335 (75% of survivors)
      were reexamined after 5 years (1997-1999) and 1952 (76% of survivors) after 10
      years (2002-2004). METHODS: The same graders performed retinal photographic
      grading in all examinations, using the Wisconsin Age-Related Maculopathy Grading
      System. Photographs of participants with ARM lesions at any of the examinations
      were subsequently regraded using a side-by-side comparison method. MAIN OUTCOME
      MEASURES: The diagnosis of incident late ARM was given if neovascular ARM or
      geographic atrophy was detected at either follow-up examination in persons free
      of these lesions at baseline. Incident early ARM was diagnosed if early ARM (soft
      indistinct or reticular drusen or combined soft distinct drusen and retinal
      pigment abnormality) was present in persons free of early and late ARM at
      baseline. Age-related maculopathy incidence was calculated using Kaplan-Meier
      methods to incorporate information from both 5- and 10-year examinations.
      Discrete logistic models were used to assess the risk of incident late ARM
      according to various baseline factors, including early ARM lesion
      characteristics. RESULTS: After excluding 72 late ARM cases present at baseline,
      2395 of 3582 subjects at risk of late ARM (67%) were reexamined at either follow
      up time point or both follow-up time points. Over the 10-year period, 72 of 2395
      subjects (3.7%) developed late ARM and 266 of 2255 subjects (14.1%) developed
      early ARM. After age standardization to the Beaver Dam Eye Study population, our
      10-year incidences of late and early ARM were 2.8% and 10.8%, respectively.
      Baseline age and early ARM lesion characteristics and severity were strong
      predictors of late ARM incidence. CONCLUSIONS: Long-term follow-up of this older
      population confirms that the risk of ARM progression is related strongly to the
      severity of early-stage lesions. The study provides evidence-based criteria for
      identifying persons at high risk of developing late ARM.

PMID- 17198853
TI  - Population-based study of early age-related macular degeneration: role of the
      complement factor H Y402H polymorphism in bilateral but not unilateral disease.
AB  - OBJECTIVE: Recently, a strong association has been observed for the complement
      factor H (CFH) Tyr402His polymorphism with early and advanced age-related macular
      degeneration (AMD) in independent non-Hispanic White, clinic-based, case-control
      studies. These studies suggest the CFH His402 allele is a major risk allele in
      early and advanced AMD, explaining 43% to 70% of all AMD in older adults. We
      utilized a population-based case-control study design of early AMD among
      Latinos/Hispanics to evaluate the CFH Tyr402His polymorphism for an association
      with early AMD phenotypes. DESIGN: Retrospective population-based case-control
      study. PARTICIPANTS: This study cohort consists of 285 early AMD cases and 570
      controls matched on age, birthplace, and smoking status. METHODS: Genotype
      determination was performed by allele-specific digestion of polymerase chain
      reaction products. MAIN OUTCOME MEASURES: Complement factor H Tyr402His
      polymorphism. RESULTS: We observed no overall statistically significant
      association with early AMD among Latinos. However, a subset of early AMD cases
      that have bilateral, not unilateral, intermediate-to-large soft macular drusen
      were 1.7 times more likely to carry either the homozygous or heterozygous His402
      genotype. CONCLUSIONS: Our data suggest that the CFH Tyr402His is not a major
      risk factor for overall early AMD in this Latino population, but may play a role
      in susceptibility to phenotypes of early AMD likely to progress to late AMD.

PMID- 17198854
TI  - Role of Helicobacter pylori in conjunctival mucosa-associated lymphoid tissue
      lymphoma.
AB  - OBJECTIVE: Conjunctiva-associated lymphoid tissue is the conjunctival equivalent
      to mucosa-associated lymphoid tissue (MALT). Mucosa-associated lymphoid tissue
      lymphoma has been shown to be associated with Helicobacter pylori. In this study,
      the prevalence and possible role of H. pylori infection in conjunctival MALT
      lymphoma were evaluated. DESIGN: Retrospective noncomparative case series.
      PARTICIPANTS: Thirteen cases of conjunctival MALT lymphoma were investigated.
      Five samples of conjunctival lymphoid hyperplasia and 20 biopsies of normal
      conjunctiva served as controls. METHODS: The specimens were investigated for the
      presence of H. pylori with immunohistochemistry (IHC) and nested polymerase chain
      reaction (PCR) techniques. For each case of conjunctival MALT lymphoma,
      information regarding gender, age at presentation, conjunctival localization, and
      information of generalized MALT lymphoma were collected. MAIN OUTCOME MEASURES:
      Detection of H. pylori and patient characteristics. RESULTS: The 13 conjunctival
      MALT lymphomas originated from 8 women and 5 men with an average age of 62 years
      (range, 25-87). Only 1 patient had evidence of systemic MALT lymphoma. H. pylori
      could not be identified in any of the conjunctival MALT lymphomas, in
      conjunctival lymphoid hyperplasia, or in normal conjunctival biopsies using IHC
      and PCR techniques. CONCLUSIONS: An association between H. pylori and localized
      conjunctival MALT lymphoma could not be verified. Antigens other than H. pylori
      may take part in the development of conjunctival MALT lymphoma.

PMID- 17198855
TI  - Complement factor H.

PMID- 17198856
TI  - Phakic IOL in children.

PMID- 17198857
TI  - Uveal melanoma in Saudi Arabia.

PMID- 17198858
TI  - Cataract surgery and glaucoma.

PMID- 17198860
TI  - Entropion surgery.

PMID- 17198861
TI  - Indocyanine green toxicity.

PMID- 17198865
TI  - Compressive optic neuropathy.

PMID- 17198866
TI  - Optical coherence tomography in optic neuritis.

PMID- 17198867
TI  - Cataract epidemiology.

PMID- 17198868
TI  - Scoring CFU-GM colonies in vitro by data fusion: a first account.
AB  - OBJECTIVE: In vitro models of hematopoiesis used in investigative hematopathology
      and in safety studies on candidate drugs, involve clonogenic assays on colony
      forming unit granulocyte macrophage (CFU-GM). These assays require live and
      unstained colonies to be counted. Most laboratories still rely on visual scoring,
      which is time-consuming and error-prone. As a consequence, automated scoring is
      highly desired. An algorithm that recognizes and scores CFU-GM colonies by data
      fusion has been developed. Some preliminary results are presented in this
      article. METHODS: CFU-GM assays were carried out on hematopoietic progenitors
      (human umbilical cord blood cells) grown in methylcellulose. Colony images were
      acquired by a digital camera and stored. RESULTS: The classifier was designed to
      process images of layers sampled from a three-dimensional (3D) domain and forming
      a stack. Structure and texture information was extracted from each image.
      Classifier training was based on a 3D colony model applied to the image stack.
      The number of scored colonies (assigned class) was required to match the count
      supplied by the human expert (class of belonging). The trained classifier was
      validated on one more stack and then applied to a stack with overlapping
      colonies. Scoring in distortion- and caustic-affected border areas was also
      successfully demonstrated. Because of hardware limitations, compact colonies in
      some cases were missed. CONCLUSIONS: The industry's scoring methods all rely on
      structure alone and process 2D data. Instead, the classifier here fuses data from
      a whole stack and is capable, in principle, of high-throughput screening.

PMID- 17198869
TI  - Roles of DRB1 *1501 and DRB1 *1502 in the pathogenesis of aplastic anemia.
AB  - OBJECTIVE: Although a number of reports have documented a significantly increased
      incidence of HLA-DR15 in aplastic anemia (AA), the exact role of HLA-DR15 in the
      immune mechanisms of AA remains unclear. We herein clarify the difference between
      DRB1( *)1501 and DRB1( *)1502, the two DRB1 alleles that determine the
      presentation of HLA-DR15, in the pathophysiology of AA. MATERIALS AND METHODS: We
      investigated the relationships of the patients( *) HLA-DRB1 allele with both the
      presence of a small population of CD55(-)CD59(-) (PNH-type) blood cells and the
      response to antithymocyte globulin (ATG) plus cyclosporin (CsA) therapy in 140
      Japanese AA patients. RESULTS: Of the 30 different DRB1 alleles, only DRB1(
      *)1501 (33.6% vs 12.8%, p(c) < 0.01) and DRB1( *)1502 (43.6% vs 24.4%, p(c) <
      0.01) displayed significantly higher frequencies among the AA patients than among
      a control. AA patients possessing HLA-DR15 tended to be old, and especially, the
      frequency of DRB1( *)1502 in patients 40 years of age and older (52.4%) was
      markedly higher than that in those younger than 40 years old (16.2%, p(c) <
      0.01). Only DRB1( *)1501 was significantly associated with the presence of a
      small population of PNH-type cells and it also showed a good response to ATG plus
      CsA therapy in a univariate analysis. A multivariate analysis showed only the
      presence of a small population of PNH-type cells to be a significant factor
      associated with a good response to the immunosuppressive therapy (p < 0.01).
      CONCLUSIONS: Although both DRB1( *)1501 and DRB1( *)1502 contribute to the
      development of AA, the methods of contribution differ between the two alleles.

PMID- 17198870
TI  - Enhanced growth of myelodysplastic colonies in hypoxic conditions.
AB  - OBJECTIVE: To determine the response of bone marrow progenitor cells from
      patients with myelodysplastic syndromes (MDS) to culture in physiologic oxygen
      tension. METHODS: Methylcellulose progenitor assays using both unfractionated
      bone marrow mononuclear cells (MNCs) and purified CD34(+) progenitors were
      performed in atmospheric oxygen (18.6% O(2)) or one of two levels of hypoxia (1%
      and 3% O(2)). Assays were performed using normal donor marrow, MDS patient
      marrow, acute myelogenous leukemia marrow or peripheral blood blasts, chronic
      phase chronic myelogenous leukemia (CML) marrow MNCs, and blast crisis CML
      peripheral blood. RESULTS: The majority of MDS samples showed decreased colony
      forming units (CFU) in 18.6% O(2) compared to normal controls, as expected.
      However, in either 1% or 3% O(2), 9 of 13 MDS samples demonstrated augmentation
      of CFUs beyond that observed in normal controls, with 6 of 13 demonstrating a
      greater than ninefold augmentation. This effect is cell autonomous, as it
      persisted after purification of CD34(+) progenitor cells. Additionally, the
      augmented response to physiologic oxygen tension is specific to MDS, as it was
      not observed in either acute or chronic myelogenous leukemia samples. CONCLUSION:
      These results suggest that the reported decrease in MDS CFUs reflects greater
      sensitivity of MDS progenitors or their progeny to the nonphysiologic oxygen
      tensions routinely used in vitro, rather than a true decrease in progenitor
      frequency. Importantly, these experiments for the first time describe an
      experimental system that can be used to study the growth of primary cells from
      patients with MDS.

PMID- 17198871
TI  - Polycythemia vera is not initiated by JAK2V617F mutation.
AB  - OBJECTIVE: The somatic JAK2(V617F) mutation is seen in most polycythemia vera
      (PV) patients; however, it is not clear if JAK2(V617F) is the PV-initiating
      mutation. METHODS: In order to examine this issue, we developed a novel real-time
      quantitative allele-specific PCR, in which allelic discrimination is enhanced by
      the synergistic effect of a mismatch in the -1 position, and a locked nucleic
      acid (LNA) nucleoside at the -2 position. RESULTS: Determination of allelic
      frequencies was reproducible (SD = 1.5%) and sensitive--0.1% mutant allele
      detected in 40 ng of DNA. The JAK2(V617F) frequency in clonal granulocytes from 3
      PV females was less than 50% (27.5 +/- 11) and in 7 females greater than 50% (75
      +/- 10.5). We also found that wild-type JAK2 BFU-E colonies from PV patients can
      grow without erythropoietin. The identification of the primary genetic lesion
      resulting in PV is essential for the development of novel therapeutic strategies.
      CONCLUSION: Our studies correlating the frequency of JAK2(V617F) mutant allele
      and clonality, as well as the presence of homozygous wild-type JAK2
      erythropoietin-independent erythroid colonies, provide compelling evidence that
      the JAK2(V617F) is not the PV-initiating mutation. This supports a model wherein
      the JAK2(V617F) mutation arises as a secondary genetic event. Furthermore, our
      results indicate that an undefined molecular lesion, preceding JAK2(V617F), is
      responsible for clonal hematopoiesis in PV. We conclude that development of
      therapeutic strategies that target the JAK2(V617F) clonal cells may not be
      sufficient for eradication of PV.

PMID- 17198873
TI  - The gamma-globin gene promoter progressively demethylates as the hematopoietic
      stem progenitor cells differentiate along the erythroid lineage in baboon fetal
      liver and adult bone marrow.
AB  - OBJECTIVE: To determine whether the difference in gamma-globin gene promoter
      methylation in terminal erythroblasts at the fetal and adult stages of
      development is a result of fetal stage-specific demethylation or adult stage
      specific de novo methylation during erythropoiesis. MATERIALS AND METHODS: Fetal
      liver- (FL, n = 2) and adult bone marrow- (ABM, n = 3) derived hematopoietic
      stem/progenitor cells and mature erythroblasts were purified by passage through a
      Miltenyi Magnetic Column followed by fluorescein-activated cell sorting (FACS)
      into subpopulations, defined by expression of CD34 and CD36 antigens.
      CD34(+)CD36(-), CD34(+)CD36(+), and CD34(-)CD36(+) subpopulations were purified
      by FACS and their degree of differentiation verified using the colony-forming
      cell assay. The methylation pattern of 5 CpG sites in the gamma-globin promoter
      region of these purified cell populations was determined using bisulfite
      sequencing. RESULTS: The gamma-globin promoter was highly methylated in the
      earliest stage of hematopoietic stem progenitor cells (CD34(+)CD36(-)) and
      methylation progressively decreased as erythroid differentiation progressed in FL
      and appears so in ABM as well. CONCLUSIONS: These data support a model in which
      differences in the methylation pattern of the gamma-globin gene in
      differentiating erythroblasts at different stages of development is the result of
      fetal stage-specific demethylation associated with transcriptional activation,
      rather than de novo methylation in the adults. The difference in the extent of
      gamma-globin gene demethylation in FL and ABM is correlated with the difference
      in gamma-globin expression at these developmental stages.

PMID- 17198872
TI  - Altered regulation of beta-like globin genes by a redesigned erythroid
      transcription factor.
AB  - OBJECTIVE: Targeted regulation of beta-like globin genes was studied using
      designer zinc finger transcription factors containing the DNA binding domain of
      the red cell specific transcription factor erythroid Kruppel-like factor (EKLF)
      fused to repression domains. METHODS: Globin gene expression was analyzed after
      introduction of the modified transcription factors into cell lines, embryonic
      stem cells and transgenic mice. RESULTS: As would be predicted, when introduced
      transiently into cells these transcription factors were effective in repressing
      the adult beta-globin promoter CACCC element, which is the natural target for
      EKLF. In murine erythroleukemia cells repression of the adult beta-globin gene
      was accompanied by a reactivation of the endogenous embryonic betaH1-globin gene.
      Studies in differentiated embryonic stem cells and transgenic mice confirmed the
      reactivation of embryonic gene expression during development. CONCLUSION: Our
      studies support a competition model for beta-globin gene expression and
      underscore the importance of EKLF in the embryonic/fetal-to-adult globin switch.
      They also demonstrate the feasibility of designer zinc finger transcription
      factors in the study of transcriptional control mechanisms at the beta-globin
      locus and as potential gene therapy agents for sickle cell disease and related
      hemoglobinopathies.

PMID- 17198874
TI  - All-trans retinoic acid induces proliferation of an irradiated stem cell
      supporting stromal cell line AFT024.
AB  - OBJECTIVE: We have previously shown that all-trans retinoic acid (ATRA) enhanced
      the maintenance of early human hematopoietic progenitor cells (HPCs) in the
      presence of an irradiated stromal cell line AFT024. In this study, we examined
      the effects of ATRA on the stromal cell component with particular reference to
      cellular proliferation and gene expression. METHODS: Irradiated AFT024 cells were
      cultured in Dulbecco's Modified Eagle's Medium supplemented with fetal bovine
      serum and were incubated with ATRA at 1 mumol/L up to 21 days. The cells were
      examined in terms of immunostaining for proliferative cell nuclear antigen (PCNA)
      and BrdU incorporation, apoptosis assay, cell cycle analysis, and gene expression
      using semiquantitative reverse-transcriptase polymerase chain reaction. RESULTS:
      In the control experiments, AFT024 cells lost their confluence in culture after
      15-Gy irradiation and were arrested in G2/M phase on days 7 and 21. ATRA restored
      the cellular confluence with an increase in proliferation on day 21 (BrdU
      incorporation: 20.6-fold; PCNA staining: 51.7-fold) with reversal of cell cycle
      arrest (S phase: 2.7-fold increase; G2/M phase: 2.0-fold decrease). There was no
      effect on apoptosis as shown by terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling staining. ATRA significantly upregulated the expression of
      cell cycle genes for checkpoint transition, including cyclin A2, B2, and aurora
      kinase B, as well as genes associated with a putative role in HPC maintenance,
      including osteopontin, HoxA5, enhancer of zeste homolog 2, and peroxisome
      proliferator-activated receptor gamma. CONCLUSION: We concluded that ATRA induced
      cellular proliferation of irradiated AFT024 cells and expression of a number of
      genes whose relevance to HPC homeostasis would have to be further examined.

PMID- 17198875
TI  - Adenoviral-mediated TGF-beta1 inhibition in a mouse model of myelofibrosis
      inhibit bone marrow fibrosis development.
AB  - Myelofibrosis is characterized by excessive deposits of extracellular matrix
      proteins, which occur as a marrow microenvironment reactive response to cytokines
      released from the clonal malignant myeloproliferation. The observation that mice
      exposed to high systemic levels of thrombopoietin (TPO) invariably developing
      myelofibrosis has allowed demonstration of the crucial role of transforming
      growth factor (TGF)-beta1 released by hematopoietic cells in the onset of
      myelofibrosis. The purpose of this study was to investigate whether TGF-beta1
      inhibition could directly inhibit fibrosis development in a curative approach of
      this mice model. An adenovirus encoding for TGF-beta1 soluble receptor (TGF-beta
      RII-Fc) was injected either shortly after transplantation (preventive) or 30 days
      post-transplantation (curative). Mice were transplanted with syngenic bone marrow
      cells transduced with a retrovirus encoding for murine TPO. All mice developed a
      myeloproliferative syndrome. TGF-beta-RII-Fc was detected in the blood of all
      treated mice, leading to a dramatic decrease in TGF-beta1 level. Histological
      analysis show that the two approaches (curative or preventive) were successful
      enough to inhibit bone marrow and spleen fibrosis development in this model.
      However, lethality of TPO overexpression was not decreased after treatment,
      indicating that in this mice model, myeloproliferation rather than fibrosis was
      probably responsible for the lethality induced by the disorder.

PMID- 17198876
TI  - Synergistic antileukemia effect of genistein and chemotherapy in mouse xenograft
      model and potential mechanism through MAPK signaling.
AB  - We investigated the antiproliferative effect of genistein, and its antileukemia
      effect in combination with cytosine arabinoside (ara-C) in acute myeloid leukemia
      (AML). Optimal dosage of genistein as single agent and in combination with ara-C
      was first determined in vitro. Genistein demonstrated a dose- and time-dependent
      inhibition of cell proliferation, induction of apoptosis, and cell-cycle arrest
      at G(2)/M phase. Gene-expression profiles revealed mitogen-activated protein
      kinase (MAPK) signaling as one of the most affected biological pathways.
      Phosphatidylinositol 3 kinase, protein kinase A, protein kinase C, MAPK kinase 4,
      KIT, PIM1, and transforming growth factor-beta receptor 1, were significantly
      downregulated by genistein. To test whether genistein could augment the
      antiproliferation activity of ara-C, two groups of severe combined
      immunodeficient mice were inoculated with NB4 and HL-60 cells, respectively,
      followed by treatment with either genistein or combination of genistein and ara
      C. The combination treatment significantly inhibited tumor growth, and improved
      survival of NB4 (p = 0.0031) and HL-60 (p = 0.0007) xenograft mice. Our present
      study highlighted the schedule-dependent synergistic antileukemia effect of
      genistein with chemotherapy in both in vitro and in vivo models. This novel
      combination could potentially be a promising regimen for treatment of AML.

PMID- 17198877
TI  - Gene-expression profiling during curcumin-induced apoptosis reveals
      downregulation of CXCR4.
AB  - OBJECTIVE: A dietary compound curcumin hardwires to multiple cellular processes,
      with suppression of cell proliferation, induction of apoptosis, and inhibition of
      metastasis considered as the major mechanisms underlying its anticancer
      properties. Based on our recent evidence that curcumin triggers cell demise in
      follicular lymphoma (FL) cells, we aimed to identify curcumin-regulated genes of
      utmost importance for the treatment of follicular lymphoma. MATERIALS AND
      METHODS: Large-scale gene-expression profiling was performed during curcumin
      triggered apoptosis (8-36 hours) in follicular lymphoma HF4.9 cells using Sentrix
      Human WG-6 BeadChips. Expression levels of selected differentially expressed
      genes were verified by quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) and immunoblotting. Chemical inhibitor studies (cyclosporin A
      and AMD3100) were performed to provide further insights into the functional
      significance of selected genes. RESULTS: Comprehensive transcriptional response
      is associated with curcumin treatment in HF4.9 cells, including differential
      expression of genes encoding apoptotic signaling proteins, tumor and metastasis
      suppressors, transcription and splicing factors, proteins involved in regulation
      of cell adhesion, migration (e.g., CXCR4), lymphoid development, or B-cell
      activation (e.g. CD20), and others. CXCR4 downregulation was confirmed by both
      qRT-PCR and immunoblotting. Importantly, curcumin induced downregulation of CXCR4
      protein also in other FL cell lines, and similar effect was observed upon
      prolonged incubation with low concentration of curcumin. AMD3100 (a selective
      CXCR4 antagonist) alone enhanced neither spontaneous nor serum-starvation-induced
      death at 24 hours of treatment, but impaired long-term cell growth in a cell line
      dependent fashion. CONCLUSIONS: To our knowledge this is the first study showing
      curcumin-induced downregulation of CXCR4, and at attainable in vivo concentration
      of the polyphenol. Other curcumin-regulated genes identified herein, e.g., CD20,
      are also seemingly pertinent to the pathophysiology of follicular lymphoma.

PMID- 17198878
TI  - Stem cell continuum: directed differentiation hotspots.
AB  - OBJECTIVE: The purpose of this study was to evaluate the technique of stem cell
      directed differentiation in the context of cell-cycle position. The hypothesis
      was that stem cells would have different sensitivities to an identical inductive
      signal through cell-cycle transit and that this would affect the outcome of its
      progeny. MATERIALS AND METHODS: Differentiation of murine marrow
      lineage(negative)rhodamine-123(low-)Hoechst-33342(low) (LRH) stem cells was
      determined at different points in cell cycle under stimulation by thrombopoietin,
      flt3 ligand, and steel factor. LRH stem cells were subcultured in granulocyte
      macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and
      steel factor at different points in cell cycle and differentiation determined 14
      days later. RESULTS: There was a significant, reproducible, and pronounced
      reversible increase in differentiation to megakaryocytes in early S-phase and to
      nonproliferative granulocytes in mid S-phase. Megakaryocyte hotspots also were
      seen on a clonal basis. Elevations of the transcription factor FOG-1 were seen at
      the hotspot along with increases in Nfe2 and Fli1. CONCLUSIONS: We show that the
      potential of marrow stem cells to differentiate changes reversibly with cytokine
      induced cell-cycle transit, suggesting that stem cell regulation is not based on
      the classic hierarchical model, but instead on a functional continuum. We propose
      that there is a tight linkage of commitment to a lineage and a particular phase
      of cell cycle. Thus, windows of vulnerability for commitment can open and close
      depending on the phase of cell cycle. These data indicate that stem cell
      differentiation occurs on a cell-cycle-related continuum with fluctuating windows
      of transcriptional opportunity.

PMID- 17198879
TI  - Effects of the CD33-targeted drug gemtuzumab ozogamicin (Mylotarg) on growth and
      mediator secretion in human mast cells and blood basophils.
AB  - OBJECTIVE: Mylotarg (gemtuzumab ozogamicin [GO]) has recently been introduced as
      a novel CD33-targeting drug in clinical hematology. However, despite efficacy, GO
      produces significant side effects including an infusion syndrome. We have
      recently shown that mast cells (MCs) and basophils (BAs) express CD33. In the
      present study, we investigated the effects of GO on growth and mediator secretion
      in MCs and BAs. METHODS: Growth-inhibitory effects of GO on neoplastic MCs (HMC
      1) and BAs (KU812) as well as cord blood-derived MC and BA progenitor cells were
      determined by counting cell numbers and the numbers of apoptotic cells. The
      amount of histamine secreted from primary MCs and BAs was measured by
      radioimmunoassay after incubation of cells with GO alone or GO together with an
      anti-immunoglobulin E (IgE) antibody. RESULTS: MCs and BAs as well as HMC-1 cells
      and KU812 cells were found to express CD33 mRNA and the CD33 protein. GO was
      found to inhibit the growth of HMC-1 cells and KU812 cells as well as stem cell
      factor-dependent differentiation of MCs and interleukin-3-induced growth of BAs
      from their cord blood-derived progenitors. The GO-induced inhibition of growth of
      neoplastic cells was found to be associated with induction of apoptosis. GO
      neither induced secretion of histamine from MCs or BAs nor upregulated the anti
      IgE-induced release of histamine in these cells. CONCLUSIONS: GO counteracts
      growth of normal and neoplastic MCs and BAs without inducing rapid release of
      histamine. The exact value of GO as a targeted drug for the treatment of high
      grade MC or BA neoplasms remains to be determined.

PMID- 17198880
TI  - Quantitative assessment of human T lymphocytes in RAG2(-/-)gammac(-/-) mice: the
      impact of ex vivo manipulation on in vivo functionality.
AB  - OBJECTIVE: Recent clinical trials of adoptive immunotherapy showed diminished
      reactivity of human T cells upon ex vivo manipulation. For a safe and effective
      clinical application of human T cells, it is necessary to improve ex vivo
      manipulation procedures and evaluate their impact on in vivo functionality.
      However, there is no preclinical model for quantitative assessment of in vivo
      functionality of human T cells. In this study, we investigated the feasibility of
      using the huPBMC- RAG2(-/-)gammac(-/-) xenogeneic mouse model. As a first
      example, we compared 3 different ex vivo culture conditions for human T cells.
      METHODS: RAG2(-/-)gammac(-/-) mice received cultured human T cells that were
      stimulated via CD3 alone or costimulated via CD28 (CD3/28) and/or human 4-1BB
      (CD3/28/4-1BB). Engraftment levels and survival of the cells were measured. The
      dynamics of the human T cell phenotypes were analyzed during culture and in vivo,
      as well as the mechanism of the xenoresponse. RESULTS: Engraftment potential was
      improved twofold for costimulation compared to CD3 alone (p < 0.001). Phenotypic
      analysis showed a strikingly similar pattern of development towards CD4(+) and
      CD8(+) effector and effector-memory cells, suggesting antigen-driven survival and
      expansion. All parameters used to analyze different effects on in vivo T-cell
      functionality, like culture condition, engraftment levels, survival of the cells
      over time, or xenogeneic graft-vs-host disease were absolutely independent of the
      distribution of the T cell population in vivo following contact with xeno
      antigen. CONCLUSION: The huPBMC-RAG2(-/-)gammac(-/-) xenogeneic transplant model
      is the most sensitive to date for in vivo functional evaluation of human T cells.

PMID- 17198881
TI  - Osteoporosis of hematologic etiology.
AB  - OBJECTIVE: Here we present evidence that overexertion of the hematopoietic system
      following chronic bleeding plays an important role in the etiology of
      osteoporosis. MATERIALS AND METHODS: C57BL/6 mice were exposed to chronic
      bloodletting (0.2 mL twice per month for 10 months), total body irradiation (900
      cGy), or aging (20-30 months old). Bone marrow from standard untreated donors was
      transplanted under the kidney capsules of all three categories of recipients to
      investigate the influence of each of these conditions on new bone marrow
      formation. Cellularity and histologic structure of developed osteohematopoietic
      sites and histomorphometry of lumbar vertebrae were studied, thus assessing the
      role of bleeding, irradiation, and old age on new bone formation and effects on
      existing bone. RESULTS: Chronic blood loss led to augmented production of
      hematopoietic microenvironment, relative reduction in the amount of generated
      bone, and activation of the bone resorptive process in the newly forming
      osteohematopoietic complex. Similar results were seen in irradiated and senescent
      mice. Activity, stimulating expansion of hematopoietic microenvironment, was
      revealed in the plasma of all three categories of experimental mice. Likewise,
      quantification of the relative amount of bone and hematopoietic areas in skeletal
      sites showed a significant reduction in bone tissue of the first lumbar vertebrae
      of chronically bled mice. CONCLUSIONS: Our experimental data, together with
      existing clinical observations documenting the role of hematopoietic
      insufficiency in the development of osteoporosis, confirm our working hypothesis
      that chronic blood loss may be the primary factor responsible for the rapid and
      consistent development of postmenopausal osteoporosis.

PMID- 17198882
TI  - Increased longevity of hematopoiesis in continuous bone marrow cultures derived
      from NOS1 (nNOS, mtNOS) homozygous recombinant negative mice correlates with
      radioresistance of hematopoietic and marrow stromal cells.
AB  - OBJECTIVE: Neuronal nitric oxide synthase (NOS1, mitochondrial NOS, neuronal NOS)
      homozygous deletion recombinant negative mice demonstrate ionizing irradiation
      resistance in vivo, attributable to the decrease in mitochondrial-localized
      production of peroxynitrite, a potent lipid toxic free radical species resulting
      from the combination of nitric oxide and superoxide. The present studies were
      designed to determine whether reduced mitochondrial generation of toxic radical
      oxygen species in NOS1-/- mice also increased the longevity of hematopoiesis in
      continuous bone marrow cultures and conferred radioresistance to cells in vitro.
      MATERIALS AND METHODS: Long-term bone marrow cultures (LTBMCs) were established
      from NOS1-/- and NOS1+/+ littermate mice. Radiation resistance of hematopoietic
      and marrow stromal cells was measured. Cell cycle analysis and measurement of
      glutathione and glutathione peroxidase were carried out on irradiated clonal bone
      marrow stromal cell lines. RESULTS: A significant increase in longevity of
      hematopoiesis was detected in NOS1-/- mouse LTBMCs for over 64 weeks in culture
      compared to 20 weeks for NOS1+/+ mouse LTBMCs (p < 0.001). Permanent bone marrow
      stromal cell lines derived from NOS1-/- mouse LTBMCs demonstrated increased
      radioresistance in vitro reflected by an increased shoulder on the survival curve
      with n = 32.15 +/- 1.21 compared to NOS1+/+ cells n = 10.47 +/- 3.2 (p = 0.0026),
      interleukin-3-dependent NOS1-/- hematopoietic progenitor cell lines also
      demonstrated decreased apoptosis after 10 Gy irradiation. Both pre- and
      postirradiation stabilization of the cellular antioxidant pool was detected in
      NOS1-/- cells. NOS1-/- cells showed a prolonged G1 cell cycle arrest after 10 Gy.
      CONCLUSIONS: Prolonged hematopoiesis in LTBMCs correlates with intrinsic
      radioresistance of hematopoietic and marrow stromal cells from NOS1-/- mice. The
      data confirm the importance to hematopoiesis of mitochondrial localized nitric
      oxide in both radioresistance and longevity of hematopoiesis in continuous bone
      marrow cultures.

PMID- 17198883
TI  - Simultaneous generation of CD34+ primitive hematopoietic cells and CD73+
      mesenchymal stem cells from human embryonic stem cells cocultured with murine OP9
      stromal cells.
AB  - OBJECTIVE: Human embryonic stem cells (hESCs) have been shown to generate CD34(+)
      primitive hematopoietic cells after several days of coculturing with the OP9
      murine stromal cell line. CD73(+) multipotent mesenchymal cells have also been
      isolated from hESC/OP9 cocultures after several weeks. We hypothesized that
      generation of CD34(+) hematopoietic cells and CD73(+) mesenchymal stem cells
      (MSCs) may follow similar kinetics, so we investigated the generation of CD73(+)
      cells in the first 2 weeks of hESC/OP9 cocultures, at a time when CD34(+) cells
      are generated. MATERIALS AND METHODS: We cocultured hESCs with OP9 cells and
      examined the time course of appearance of human CD34(+) and CD73(+) cells using
      flow cytometry. We tested the hematopoietic progenitor potentials of CD34(+)
      cells generated using hematopoietic colony-forming assays, and the multipotent
      mesenchymal properties of CD73(+) cells generated using in vitro differentiation
      assays. RESULTS: We observed that in the first 2 weeks of the hESC/OP9 coculture
      system CD34(+) hematopoietic and CD73(+) MSC generation follows a similar
      pattern. We sorted the CD34(+) cells and showed that they can generate
      hematopoietic progenitor colonies. Starting with cocultured cells on day 8, and
      through an enrichment procedure, we also could generate a pure population of
      MSCs. These hESC-derived MSCs had typical morphological and cell surface marker
      characteristics of adult bone marrow-derived MSCs, and could be differentiated
      toward osteogenic, adipogenic, and chondrogenic cells in vitro, a hallmark
      property of MSCs. CONCLUSIONS: OP9 cells when cocultured with hESCs support
      simultaneous generation of CD34(+) primitive hematopoietic cells and CD73(+) MSCs
      from hESCs.

PMID- 17198884
TI  - Donor CD4+ T-cell production of tumor necrosis factor alpha significantly
      contributes to the early proinflammatory events of graft-versus-host disease.
AB  - OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is an old foe in allogeneic
      bone marrow transplantation (allo-BMT) promoting acute graft-versus-host disease
      (aGVHD). We investigated to what extent donor T cells contribute to TNFalpha
      production. METHODS: Lethally irradiated B6D2F1 mice were transplanted with bone
      marrow (BM) and T cells from syngeneic B6D2F1 or allogeneic B6 donors and
      assessed for cytokine production, aGVHD, and survival. RESULTS: Analysis of serum
      TNFalpha kinetics in recipients of allogeneic B6 wild-type BM and wild-type T
      cells revealed that TNFalpha levels peaked around day 7 after allo-BMT, whereas
      TNFalpha was undetectable in syngeneic controls. TNFalpha was produced by both
      host and donor cells. Further exploration showed that specifically donor CD4(+)
      but not CD8(+) T cells were the primary donor cell source of TNFalpha at this
      early time point; numbers of TNFalpha expressing splenic CD4(+) T cells were
      higher than CD8(+) T cells 7 days after allo-BMT, and maximal serum TNFalpha
      levels were detected following allo-BMT with only CD4(+) T cells compared to
      levels found in allogeneic recipients of only wild-type CD8(+) or to only CD4(+)
      TNFalpha(-/-) T cells. Concurrent with increased TNFalpha levels, early clinical
      aGVHD and mortality were more severe following allo-BMT with either wild-type
      CD4(+) and CD8(+) or CD4(+) T cells only. CONCLUSION: Our data demonstrate that
      in addition to residual host cells donor CD4(+) T cells significantly contribute
      to the proinflammatory cytokine milieu engendered early after allo-BMT through
      the production of TNFalpha. These findings support strategies focusing on
      TNFalpha neutralization as primary treatment for aGVHD.

PMID- 17198885
TI  - Sirolimus promotes tolerance for donor and recipient antigens after MHC class II
      disparate bone marrow transplantation in rats.
AB  - OBJECTIVE: Mixed chimerism after allogeneic bone marrow transplantation (BMT)
      promotes immunologic tolerance. Graft-vs-host disease (GvHD) can occur when
      immunosuppressive control of the graft fails. Here we evaluate the influence of
      concurrent immunosuppression after irradiation-based induction therapy on
      development of tolerance and GvHD. METHODS: Conditioning was performed by
      different doses of total body irradiation (TBI) in a major histocompatibility
      complex (MHC) class II disparate rat BMT model. Animals received subsequent
      immunosuppression with either cyclosporine A (CsA) or sirolimus.
      Nonresponsiveness toward donor and recipient antigens was demonstrated by
      development of mixed chimerism and/or GvHD. RESULTS: Administration of 10 Gy of
      TBI prior to BMT alone was associated with severe GvHD. Induction therapy with 8
      Gy of TBI alone led to graft rejection in the long-term. Two weeks of
      immunosuppression with CsA after 8 Gy of TBI resulted in transient chimerism, but
      was finally associated with a combination of fatal GvHD and graft rejection. Six
      gray of TBI with CsA treatment for 14 or 28 days caused only mild GvHD, but did
      not lead to stable chimerism. In contrast, treatment with sirolimus was
      associated with stable chimerism after 8 Gy of TBI (14-day course) and 6 Gy of
      TBI (28-day course) accompanied by a low incidence of GvHD. CONCLUSIONS: In
      contrast to CsA, sirolimus facilitates development of tolerance after MHC class
      II disparate BMT and irradiation-based conditioning, with a low risk of GvHD.
      Therefore, sirolimus has promising characteristics for inclusion in
      immunosuppressive protocols.

PMID- 17198886
TI  - Development of an anti-porcine CD34 monoclonal antibody that identifies
      hematopoietic stem cells.
AB  - OBJECTIVES: The isolation of porcine hematopoietic stem cells (HSC) would be an
      important step toward development of porcine-to-human chimerism for induction of
      tolerance in clinical xenotransplantation. CD34 is a common marker of HSC and has
      not been developed as a marker in pigs. In this study we have generated and
      characterized a monoclonal antibody (mAb) that identifies porcine CD34 on a
      subset of porcine bone marrow (BM) stem/progenitor cells. METHODS: The porcine
      CD34 gene was cloned and a recombinant protein produced. An anti-porcine CD34 mAb
      was produced that could detect both the recombinant protein and a subset of
      porcine BM cells. The CD34(+) cells were phenotyped by lineage and HSC associated
      markers. Furthermore, the CD34(+) cells were analyzed by colony-forming unit
      (CFU) assay. RESULTS: Two splice variants of the porcine CD34 gene were cloned
      and a recombinant protein produced for mAb production. The mAb developed can
      detect both the recombinant protein and the native CD34 protein on a range of pig
      tissues, including BM. This subset of BM cells was negative for hematopoietic
      lineage makers, including CD3, CD14, and CD21 and positive for other known
      porcine HSC markers, including CD90, CD172a, histocompatibility complex (MHC)
      class I, and MHC class II. Moreover, the CD34(+) BM cells were enriched for
      multilineage progenitor cells as determined by CFU assay. CONCLUSIONS: Similar to
      human and mouse CD34, pig CD34 detects a subset of BM progenitor cells. This mAb
      will now provide a means for isolating porcine CD34(+) cells to be further
      analyzed for HSC activity and to assess their potential to develop pig-to-human
      chimeras to induce xenograft tolerance.

PMID- 17198887
TI  - Calcaneal fractures: what the surgeon needs to know.
AB  - The calcaneus is an uncommonly fractured bone that plays a critical role in foot
      biomechanics, weight-bearing, and the ability to wear a shoe. The radiologist
      acts as a consultant during screening, operative planning, and follow-up imaging
      of these often complex injuries. Effective communication between radiologist and
      surgeon requires an understanding of calcaneal anatomy, goals of surgical
      reduction, and factors that affect patient management and outcomes. In the
      following pictorial review we will discuss radiologic
      screening/classification/characterization and their correlation with surgical
      management and patient morbidity.

PMID- 17198888
TI  - Evaluation of collateral ligament injuries of the metacarpophalangeal joints with
      magnetic resonance imaging and magnetic resonance arthrography.
AB  - Injuries of the collateral ligaments of the metacarpophalangeal (MCP) joints of
      the hand require accurate diagnosis and prompt treatment to prevent loss of
      function. The most common and well-known collateral ligament injury is injury to
      the ulnar collateral ligament of the first MCP joint of the hand, often referred
      to as a gamekeeper injury. Although less common, injuries involving the
      collateral ligaments of the second through fifth digits and the radial collateral
      ligament of the first digit also occur. The diagnosis of collateral ligament
      injury is often made clinically, however, magnetic resonance imaging and magnetic
      resonance arthrography of the MCP joints can be very useful in the evaluation of
      severity of the injury. This provides important information for the hand surgeon
      and aids in treatment planning. Imaging of the collateral ligaments requires
      small fields of view and several technical considerations can provide improved
      image quality. These factors will be discussed and illustrated in this article.

PMID- 17198889
TI  - Integrated CT-PET imaging of esophageal cancer: unexpected and unusual
      distribution of distant organ metastases.
AB  - CT-PET imaging is being increasingly used for the initial staging, assessment of
      treatment response, and follow-up of patients with esophageal carcinoma,
      primarily because of its superior detection of distant metastases compared to
      conventional methods. Our recent experience has shown that metastases from
      esophageal cancer can occur in unusual locations and have an unexpected
      presentation. Recognition of the distribution and appearance of esophageal
      metastases is important for optimal image interpretation in order to avoid
      confusion with more benign disease. This article reviews the location and
      appearance of metastases detected by CT-PET imaging in patients with esophageal
      cancer either at presentation or after preoperative or definitive chemoradiation
      therapy.

PMID- 17198890
TI  - Abdominal hernias: imaging review and historical perspectives.
AB  - Many eminent anatomists originally described abdominal hernias, some of which are
      still named after the original authors. In this article, the radiologic features
      of abdominal hernias are reviewed as imaged on x-ray, ultrasound, multidetector
      computed tomography, and magnetic resonance imaging. Recognition of the typical
      appearance of various types of abdominal hernias and associated adverse features
      such as bowel obstruction, perforation, strangulation, or volvulus formation can
      help in formulating an accurate diagnosis. A short biography of the scientists
      associated with eponymous hernias and their other important scientific
      contributions are also described.

PMID- 17198891
TI  - Infected dermoid sinus tract mimicking recurrent sinusitis in an adolescent male.
AB  - Nasal dermoid sinus cysts are the most common congenital midline nasofrontal
      masses, but they can easily be confused with simple recurrent sinusitis upon
      clinical presentation. We report the case of a 14-year-old male who was initially
      diagnosed with frontal sinusitis and treated with antibiotics but, after multiple
      episodes of recurrence, was later sent for imaging. Computed tomography and
      magnetic resonance imaging showed an infected dermoid sinus tract. Subsequent
      surgery removed the mass and pathologic investigation proved the diagnosis.

PMID- 17198892
TI  - Synovial cyst: an uncommon cause of back pain.
AB  - Synovial cyst is an uncommon cause of back pain and radiculopathy. This case
      report describes the magnetic resonance imaging findings of two lumbar synovial
      cysts with special emphasis on the differential diagnoses of other extradural
      cystic lesions.

PMID- 17198893
TI  - A time for resolutions: healthy body images.

PMID- 17198894
TI  - Neurodevelopmental outcome in preschool survivors of complex congenital heart
      disease: implications for clinical practice.
AB  - INTRODUCTION: The purpose of this study was to describe the neurodevelopmental
      outcome of preschool survivors of Hypoplastic Left Heart Syndrome (HLHS) and
      Transposition of the Great Arteries (TGA) in the modern surgical era. METHODS: A
      cross-sectional design was used to evaluate 26 children (13 HLHS, 13 TGA), ages
      3.5 to 6 years, at a Midwestern children's hospital. Measures included McCarthy
      Scales of Children's Abilities, Woodcock Johnson III Tests of Achievement,
      Developmental Test of Visual-Motor Integration, Receptive One-Word Vocabulary
      Test, Expressive One-Word Vocabulary Test, and Child Behavior Checklist. RESULTS:
      Although intelligence quotient scores fell within the average range for both
      groups (TGA=110.5 vs. HLHS=97), the difference between groups was clinically
      meaningful (effect size= .79). The HLHS group showed more problems than did the
      TGA group with visual-motor skills, expressive language, attention, and
      externalizing behavior. DISCUSSION: Results suggest that even in the modern
      surgical era, regular developmental screening for these patients is critical.
      Pediatric nurse practitioners play an important role in educating parents about
      the potential developmental risks to these children.

PMID- 17198895
TI  - The eating and physical activity habits of inner-city adolescents.
AB  - INTRODUCTION: The purposes of this study were to (a) analyze the body mass index
      (BMI) percentile and eating and physical activity habits of adolescents, viewing
      them by sex, ethnicity, household type, and foreign-born or born in the United
      States, and (b) evaluate diet and activity analysis software for use by
      practitioners and adolescent clients. METHOD: A descriptive-correlational study
      of 74 adolescents from low-income households completed a 24-hour recall of their
      foods, drinks, and activities, which were analyzed using MyPyramidTracker
      software. Data were analyzed using parametric and nonparametric methods to test
      associations and conduct between-group comparisons. RESULTS: Girls, Hispanics,
      adolescents living with single-parent mothers, and those who were foreign born
      had the highest mean BMI percentiles and the least healthy eating and physical
      activity habits. BMI percentile fell as daily calorie expenditure rose.
      MyPyramidTracker software is suitable for use by adolescents and their family
      members. DISCUSSION: To contribute to the reversal of national trends of
      increasing overweight status among adolescents, practitioners can focus their
      teaching, counseling, and advocacy on adolescents in these groups.

PMID- 17198896
TI  - Parent-infant co-sleeping and its relationship to breastfeeding.
AB  - Co-sleeping can provide numerous benefits for both the parent(s) and the infant.
      Perhaps the greatest advantage lies in its promotion of breastfeeding, an act
      widely recognized for its benefits to both the mother and infant. However, risks
      also are associated with co-sleeping, prompting many researchers to examine the
      safety of its practice. Pediatric nurse practitioners need to be informed on
      issues related to co-sleeping in order to educate parents regarding its risks and
      benefits, to assess the safety of an established sleeping environment, and to be
      aware of its prevalence in their patient populations. A review of the literature
      is presented to inform pediatric nurse practitioners about varied definitions of
      co-sleeping, the reasons why some parents engage in the practice, cultural
      preferences for co-sleeping, associated risks and benefits, and its relationship
      to breastfeeding.

PMID- 17198897
TI  - State regulations for the pediatric nurse practitioner in acute care.
AB  - INTRODUCTION: In response to economic factors affecting health care costs in
      caring for acutely ill children, pediatric nurse practitioner (PNP) practice has
      expanded to include the acute care pediatric nurse practitioner (PNP-AC). With
      this change in practice and in educational preparation, there have been changes
      in credentialing, certification, and, in some cases, state regulations. This
      study was conducted to clarify the state regulations for the PNP-AC. METHOD: A
      survey of the practice chairs, executive directors, or both, from each state
      Board of Nursing and the District of Columbia (n=51) was performed to determine
      whether PNP-ACs are recognized in each state and if not, what they would need to
      do to become eligible for recognition. RESULTS: The majority of states (31)
      require that PNP-ACs take the AC certification examination, and 10 require the
      primary care examination. The remainder of the states have variations in their
      requirements. DISCUSSION: Because this is an area that is changing rapidly, PNPs
      working in acute care settings need to stay abreast of changes in their state
      requirements.

PMID- 17198898
TI  - Childhood asthma part one: initial assessment, diagnosis, and education.

PMID- 17198899
TI  - A Swashbuckling film not starring Johnny Depp.

PMID- 17198900
TI  - Oh, no! The newborn screen is positive!

PMID- 17198901
TI  - Evidence-based practice in nursing: bridging the gap between research and
      practice.

PMID- 17198902
TI  - Improving influenza vaccine compliance through patient education for patients
      with cystic fibrosis.

PMID- 17198903
TI  - Health care quality and outcome guidelines for nursing of children and families:
      implications for pediatric nurse practitioner practice, research, and policy.

PMID- 17198904
TI  - Bovine casein hydrolysate (c12 Peptide) reduces blood pressure in prehypertensive
      subjects.
AB  - BACKGROUND: About one in four adults suffer from prehypertension. People with
      prehypertension are at risk of developing hypertension, being a biomarker for
      cardiovascular disease risk. The use of milk-derived protein hydrolysates
      containing peptides with angiotensin-converting enzyme (ACE) inhibiting
      properties may reduce blood pressure (BP) and thus the risk of developing
      hypertension. METHODS: We investigated the BP-lowering effect of a casein-derived
      protein hydrolysate (C12 Peptide) during a 4-week intervention period in
      prehypertensive subjects. After a 2-week run-in period, 48 Taiwanese volunteers
      were randomly assigned to either placebo or C12 Peptide tablets for 4 weeks,
      followed by a 2-week off-treatment period. After the run-in period, BP was
      measured weekly. RESULTS: Baseline values for systolic BP (mean +/- SEM) in the
      placebo and C12 Peptide groups were 137.1 +/- 3.1 and 137.9 +/- 2.4 mm Hg,
      respectively; those for diastolic BP were 85.2 +/- 2.1 and 86.9 +/- 2.0 mm Hg,
      respectively. Four weeks repeated daily intake of 3.8 g C12 Peptide reduced
      significantly systolic and diastolic BP by 10.7 +/- 1.6 mm Hg and 6.9 +/- 1.2 mm
      Hg, respectively, compared to baseline. Furthermore, plasma angiotensin II and
      aldosterone levels were reduced significantly (P < .05). The placebo group showed
      a BP reduction of 3.6 +/- 2.4 and 2.7 +/- 1.6 mm Hg in systolic and diastolic BP,
      respectively (P = not significant). No evidence of side effects was observed.
      CONCLUSIONS: This study shows that C12 Peptide reduces BP in prehypertensive
      people.

PMID- 17198905
TI  - Population-based examination of the interaction of primary hypertension and
      obesity in South Carolina.
AB  - Recent studies have demonstrated that the prevalence of primary hypertension
      (HTN) among children is higher than early estimates of 25%. The prevalence of
      obesity has more than doubled between 1980 and 2000, from 5% to 11%. To examine
      racial differences in the prevalence and progression of comorbid essential HTN
      and obesity for children 0 to 21 years of age, onset age distribution,
      controlling for widely acknowledged gender differences, a statewide Medicaid
      claims database was used. Results indicate that the prevalence rate of HTN in the
      general pediatric population treated during the decade between 1995 and 2004 with
      Medicaid was 3.7% for essential HTN, or 90% of the total diagnosed HTN cases.
      Just more than half were first diagnosed with HTN with no gender or ethnic
      differences, mean age of onset was 14 to 15 years of age for HTN and 12 to 15
      years of age for obesity, but with the mean age of onset for both conditions
      increasing with time. Development of the comorbid conditions takes less than 2
      years regardless of which condition is diagnosed first. African Americans
      demonstrate more rapid onset of obesity when HTN is diagnosed first, and both
      males and African Americans show more rapid onset of HTN when obesity is
      diagnosed first. This study is the first population-based study to include such a
      large cohort of pediatric patients who are both hypertensive and obese with
      information during 10 years. Pediatric males and African Americans are important
      groups to monitor closely in the diagnostic and treatment phases for comorbid HTN
      and obesity.

PMID- 17198906
TI  - Aliskiren, an orally effective renin inhibitor, provides antihypertensive
      efficacy alone and in combination with valsartan.
AB  - BACKGROUND: By blocking the renin-angiotensin-aldosterone system (RAAS) at its
      rate-limiting step, renin inhibition may provide improved RAAS suppression. We
      investigated the blood pressure (BP)-lowering effects of the oral direct renin
      inhibitor aliskiren, alone or in combination with the angiotensin receptor
      blocker valsartan. METHODS: In this multicenter, randomized, placebo-controlled,
      8-week trial, 1123 patients with mild-to-moderate hypertension underwent a 3 to 4
      week single-blind placebo run-in and were then randomized in a modified factorial
      study design to receive once-daily, double-blind oral treatment with placebo,
      aliskiren monotherapy (75, 150, or 300 mg), valsartan monotherapy (80, 160, or
      320 mg), aliskiren and valsartan in combination, or valsartan/hydrochlorothiazide
      (160/12.5 mg). The primary efficacy variable was the change from baseline in mean
      sitting diastolic BP (DBP) at endpoint. RESULTS: Once-daily oral treatment with
      aliskiren 300 mg significantly (P < .0001) lowered mean sitting DBP and systolic
      BP (SBP) compared with placebo; aliskiren monotherapy demonstrated a safety and
      tolerability profile comparable to placebo. Changes in DBP and SBP were fitted to
      a first-order dose-response surface (lack-of-fit test, P = .65), which showed
      that aliskiren and valsartan alone and in combination produced dose-related
      reductions in DBP and SBP. Coadministration of aliskiren and valsartan produced a
      greater antihypertensive effect than either drug alone, comparable in magnitude
      to the effect of valsartan/hydrochlorothiazide, with similar tolerability to the
      component monotherapies and to placebo. CONCLUSIONS: Aliskiren monotherapy
      provides antihypertensive efficacy and placebo-like tolerability in patients with
      hypertension. Aliskiren and valsartan in combination may provide additive BP
      lowering effects with maintained tolerability.

PMID- 17198907
TI  - High systolic blood pressure is associated with Val/Val genotype in the catechol
      o-methyltransferase gene. The Nord-Trondelag Health Study (HUNT).
AB  - BACKGROUND: The catechol-O-methyltransferase (COMT) gene contains a functional
      polymorphism, Val158Met. A few studies on animals have shown a relationship
      between the COMT gene and BP, but whether this exists in human beings is unclear.
      The aim of this study was to evaluate the relationship between codon 158 COMT
      gene polymorphism and BP in a population-based cohort. METHODS: In the 1995-97
      Nord-Trondelag Health Study (HUNT), the association between Val/Met polymorphism
      at the COMT gene and BP was evaluated in a group of 2966 nondiabetic individuals.
      RESULTS: Among the 2591 individuals without current use of antihypertensive
      drugs, systolic BP > or =140 mm Hg was more likely among persons with Val/Val
      genotype compared with the other genotypes (44.8% v 39.1%, P = .02). In the
      multivariate analysis the prevalence odds ratio for having the Val/Val genotype
      was 1.63 (95% CI = 1.18 to 2.24) among individuals with systolic BP > or =160 mm
      Hg compared with those with systolic BP <140 mm Hg. Val/Val genotype was also
      more likely (OR = 1.30, 95% CI = 1.04 to 1.63) among individuals with
      hypertension (as defined by use of antihypertensive medication, systolic BP > or
      =140 mm Hg, or diastolic BP > or =90 mm Hg) than among those with normal BP.
      CONCLUSIONS: Based on the study findings, the Val/Val genotype appears to be
      associated with a higher prevalence of increased systolic BP compared with the
      Met/Met or Met/Val genotypes at the COMTgene.

PMID- 17198908
TI  - Studies of an association in boys of blood pressure and the Y chromosome.
AB  - BACKGROUND: Variations in the Y chromosome have shown significant, albeit
      inconsistent, associations with hypertension in men. Studies of peripubertal
      subjects might reveal more information on the origins of the Y chromosome's
      influence on blood pressure (BP). In the current study, we examined the
      association of a HindIII restriction site on the Y chromosome with BP in a cohort
      of young men. METHODS: Pubertal growth-based analyses were performed in 80
      unrelated males with multiple measurements spanning time points beginning before
      and extending to after their pubertal growth. Blood pressure, height, and weight
      were measured approximately every 6 months. The period of pubertal growth was
      used to approximate the time for puberty. The association of the HindIII
      restriction site to systolic and diastolic BP was determined using a mixed model
      ANOVA. RESULTS: Estimated systolic and diastolic BPs were higher in HindIII(-)
      males in the period before, as well as in the period after pubertal growth
      (systolic BP 2.6 +/- 1.3 mm Hg higher, P < .05), and diastolic BP 2.3 +/- 1.2 mm
      Hg higher, P = .050). In addition, HindIII(-) males were younger at onset of peak
      height velocity (12.7 +/- 0.1 v 13.3 +/- 0.1 years, P < .001). In African
      Americans, an earlier age of maximal height velocity was associated with a higher
      systolic and diastolic BP (P < .05 and .02, respectively). CONCLUSIONS: The
      results suggest that variations in genes on the Y chromosome may affect BP in
      peripubertal males, possibly even before onset of puberty.

PMID- 17198909
TI  - The G-231A polymorphism in the endothelin-A receptor gene is associated with
      lower aortic pressure in patients with dilated cardiomyopathy.
AB  - BACKGROUND: The endothelin system (ES) plays an important role in blood pressure
      (BP) regulation and also in the pathophysiology of idiopathic dilated
      cardiomyopathy (DCM). Recently, we demonstrated that a genetic polymorphism in
      the endothelin A (ET(A)) receptor gene was associated with survival in DCM
      patients. The aim of this study was to determine whether polymorphisms in the
      ET(A) receptor gene might be associated with the severity of DCM. METHODS: One
      hundred twenty-four consecutively recruited unrelated patients with DCM, who
      underwent a detailed phenotyping protocol, were genotyped for the ET(A) receptor
      G-231A polymorphism using a hybridization technique with allele-specific
      oligonucleotides. RESULTS: The exon 1 G-231A polymorphism of the ET(A) receptor
      gene, upstream of the translation start site, was significantly associated with
      directly measured intra-aortic pressure in that -231A allele carriers had
      significantly lower systolic (P = .0043), as well as mean (P = .0016) and
      diastolic (P = .0041) aortic pressure compared to noncarriers. The association of
      ET(A) G-231A with aortic pressure was independent from other factors such as
      prior medication, left ventricular end-diastolic diameter, age, gender, and New
      York Heart Association (NYHA) functional classification. However, no such
      association was seen for cuff BP and survival rates were not significantly
      different between -231A allele carriers and -231G homozygotes (log rank test, P =
      .66). No significant association with any other parameter investigated in the
      present study could be observed, even when men and women were analyzed
      separately. CONCLUSIONS: Our results suggest an association of genetic variation
      in the ET(A) receptor gene with aortic pressure in patients with DCM.

PMID- 17198910
TI  - Increased expression and activity of phospholipase C in renal arterioles of young
      spontaneously hypertensive rats.
AB  - BACKGROUND: The aims of this study were to document the presence of phospholipase
      C (PLC) isozymes beta(1), gamma(1), and delta(1) in freshly isolated renal
      glomeruli and resistance vessels, to compare their expression and activity to
      that in aorta, and to contrast values between 6-week-old Wistar-Kyoto (WKY)
      controls and 6-week-old spontaneously hypertensive rats (SHR) during the
      developmental phase of genetic hypertension. METHODS: Aorta, preglomerular
      arterioles, and glomeruli were isolated from 6-week-old rats using standard
      techniques. PLC isozyme protein level and activity were determined with Western
      blot analysis and by measuring inositol 1, 4, 5-trisphosphate (IP(3)) production,
      respectively. RESULTS: Immunoblots indicate that all three PLC isozymes examined
      are detectable in freshly isolated preglomerular arterioles, glomeruli, and
      aorta. Increased levels of PLC-beta(1), and -delta(1) were found in all tested
      vascular tissues of SHR v WKY. No strain difference was noted for PLC-gamma(1).
      The relative abundance for both groups was glomeruli > preglomerular arterioles =
      aorta. The strain difference in protein expression correlated with increased PLC
      activity in each vascular bed of SHR. CONCLUSIONS: Protein levels of PLC-beta(1)
      and -delta(1) and PLC activity are upregulated in the systemic and renal
      vasculature in 6-week-old SHR, suggesting a role in exaggerated vascular
      reactivity during the development of genetic hypertension. A more complete
      understanding of the physiologic roles of PLC isozymes and their contributions to
      specific aspects of cellular function should advance our understanding of
      vascular tone/reactivity and hypertrophy/remodeling in normal and hypertensive
      states.

PMID- 17198911
TI  - Abnormally increased endothelin-1 in plasma during the night in obstructive sleep
      apnea: relation to blood pressure and severity of disease.
AB  - BACKGROUND: The mechanisms involved in development and maintenance of
      hypertension in obstructive sleep apnea (OSA) are not clarified. We hypothesize
      that patients with OSA have an abnormal nocturnal level of some vasoactive
      hormones during the night. METHODS: We studied 32 patients with OSA and 19
      healthy control subjects during The night-time with serial determinations of
      endothelin-1 (ENDO-1), angiotensin II (Ang II), renin (PRC), aldosterone (ALDO)
      in plasma, and blood pressure (BP), and oxygen saturation. RESULTS: Patients with
      OSA had a higher plasma level of ENDO than healthy controls and the mean
      nocturnal level of ENDO correlated significantly to the apnea-hypopnea index
      (AHI) as a measure of the severity of OSA. This correlation remained
      statistically significant after analysis in a general linear model with
      correction for confounders. Patients with OSA also had a significantly higher BP
      than healthy controls and the ambulatory BP correlated positively to the AHI in
      patients with OSA. No significant differences were measured in Ang II, PRC, and
      ALDO between the two groups. The correlation between AHI and ENDO supports OSA as
      a stimulus of endothelin release or increased endothelin levels contributing to
      the severity of OSA. CONCLUSIONS: Endothelin seems to be a pathogenic factor in
      generating hypertension in OSA.

PMID- 17198912
TI  - Involvement of Ras-regulated myosin light chain phosphorylation in the captopril
      effects in spontaneously hypertensive rats.
AB  - BACKGROUND: Early treatment with captopril prevents the development of
      hypertension by inhibiting the generation of angiotensin II and smooth muscle
      contraction. Although smooth muscle contraction is regulated by myosin light
      chain phosphorylation (MLC-P), the role of MLC-P in captopril effects in
      hypertension has not been described. Therefore, we treated spontaneously
      hypertensive rats (SHR) with captopril and investigated the effects of this agent
      on downstream signaling. METHODS: Male SHR (n = 12) were treated with captopril
      (3.7 mmol/L in drinking water) beginning in utero and continuing up to 12 weeks
      of age. Age- and sex-matched untreated SHR and Wistar-Kyoto (WKY) rats were used
      as controls. Rats were split into three subgroups and were sacrificed at 12, 18,
      or 24 weeks of age. Systolic blood pressure, left ventricular weight, and body
      weight were measured. Mesenteric arteries were removed for histologic and
      biochemical studies. RESULTS: At 12 weeks, captopril significantly decreased
      systolic blood pressure (from 198 +/- 10 to 125+/-16 mm Hg), reduced left
      ventricular weight-to-body weight ratios (from 2.94 +/- 0.06 to 2.17 +/- 0.08
      mg/g), and prevented vascular remodeling in mesenteric arteries in SHR. Ras
      expression, extracellular receptor kinase phosphorylation (ERK-P), myosin light
      chain kinase (MLCK) expression, and MLC-P were all significantly increased in
      mesenteric arteries in untreated SHR compared with WKY rats. Early captopril
      treatment in SHR significantly inhibited Ras and MLCK expression at all ages and
      decreased ERK-P and MLC-P at 12 and 18 weeks in mesenteric arteries. CONCLUSIONS:
      These data demonstrate that the antihypertensive effects of captopril are
      correlated with inhibition of Ras-regulated ERK activation, MLCK expression, and
      MLC-P.

PMID- 17198913
TI  - Inadequate cytoplasmic antioxidant enzymes response contributes to the oxidative
      stress in human hypertension.
AB  - Untreated hypertensive patients show increased oxidative stress and decreased
      antioxidant enzyme activity in mononuclear cells. Therefore, the objective of
      this study was to determine whether or not the low antioxidant enzyme activity
      observed in mononuclear cells of hypertensive subjects is in part dependent on a
      defective activity of antioxidant mechanisms. Activity and mRNA level of
      antioxidant enzymes, CuZn- and Mn-superoxide dismutases, catalase, glutathione
      peroxidase type 1, and glutathione reductase were simultaneously measured in
      mononuclear cells of controls (n = 38) and hypertensive subjects (n = 35), in the
      absence of and during antihypertensive treatment. An increase in oxidative stress
      and a decrease in the activity of cytoplasmic enzymes were observed in untreated
      hypertensive patients. Concurrently, CuZn-superoxide dismutase and glutathione
      reductase mRNA levels were significantly reduced, and glutathione peroxidase type
      1 mRNA was slightly reduced. In contrast, increased activity and mRNA levels of
      the mitochondrial Mn-superoxide dismutase were observed. Antihypertensive
      treatment, nonpharmacologic with or without a drug regimen of beta-blocker or
      angiotensin AT1 receptor blocker was administered for a 3-month period.
      Afterward, after the improvement in oxidative stress during treatment, a recovery
      of the cytoplasmic antioxidant enzymatic activity and a more profound decrease in
      mRNA levels were observed for CuZn-superoxide dismutase, glutathione peroxidase
      type 1, and glutathione reductase. Meanwhile mitochondrial enzymatic activity
      decreased, as did the mRNA level. The inadequate response of the main
      cytoplasmatic antioxidant systems, as well as of the enzymes participating in the
      maintenance of glutathione levels, may contribute to the vulnerability of
      hypertensives to oxidative stress.

PMID- 17198914
TI  - Enhanced plasma soluble CD40 ligand levels in essential hypertensive patients
      with blunted nocturnal blood pressure decrease.
AB  - BACKGROUND: Hypertensives with a blunted nocturnal blood pressure (BP) decrease
      have increased risk of developing atherosclerotic disease. Soluble CD40 ligand
      (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage.
      Therefore, we evaluated the relationship between circulating sCD40L levels,
      circadian BP profile, and early carotid atherosclerosis in essential
      hypertensives. METHODS: Plasma sCD40L concentrations were assessed in two groups
      of 25 never-treated hypertensives, without additional cardiovascular risk
      factors, differentiated on the basis of a nocturnal decrease of BP either of >10%
      (dippers) or <10% (nondippers) of daytime values, and in 25 matched
      normotensives. Carotid intima-media thickness (IMT) was also measured in all
      participants. RESULTS: Plasma sCD40L concentrations were higher in nondippers
      (4.9 +/- 1.2 ng/mL) than in dippers (3.7 +/- 0.7, P = .0005) and controls (1.6 +/
      0.6, P < .0001). These latter had lower sCD40L concentrations than dippers (P <
      .0001). The IMT was higher in both hypertensive groups than in normotensives (P <
      .0001). In the entire hypertensive population IMT directly correlated with
      circulating levels of sCD40L (r = 0.365, P = .01) and inversely correlated with
      nocturnal systolic BP decreases (r = -0.286, P = .043). In a multivariate
      regression analysis sCD40L was the main determinant of IMT (r(2) = 0.157, P =
      .004). CONCLUSIONS: Nondippers have enhanced plasma sCD40L levels, which may
      contribute to their increased susceptibility to develop vascular damage.

PMID- 17198916
TI  - Role of Ca2+-activated K+ channels on adrenergic responses of human saphenous
      vein.
AB  - BACKGROUND: We studied the participation of K(+) channels on the adrenergic
      responses in human saphenous veins as well as the intervention of dihydropyridine
      sensitive Ca(2+) channels on modulation of adrenergic responses by K(+) channels
      blockade. METHODS: Saphenous vein rings were obtained from 40 patients undergoing
      coronary artery bypass surgery. The vein rings were suspended in organ bath
      chambers for isometric recording of tension. RESULTS: Iberiotoxin (10(-7) mol/L),
      an inhibitor of large conductance Ca(2+)-activated K(+) channels, and
      charybdotoxin (10(-7) mol/L), an inhibitor of both large and intermediate
      conductance Ca(2+)-activated K(+) channels, enhanced the contractions elicited by
      electrical field stimulation and produced a leftward shift of the concentration
      response curve to norepinephrine. In contrast, the inhibitor of small conductance
      Ca(2+)-activated K(+) channels apamin (10(-6) mol/L) did not modify the
      contractile response to electrical field stimulation or norepinephrine. In the
      presence of the dihydropyridine Ca(2+)-channel blocker nifedipine (10(-6) mol/L),
      iberiotoxin and charybdotoxin failed to enhance the contractile responses to
      electrical field stimulation and norepinephrine. CONCLUSIONS: The results suggest
      that large conductance Ca(2+)-activated K(+) channels are activated by
      stimulation with norepinephrine to counteract the adrenergic-induced contractions
      of human saphenous vein. Thus, inhibition of these channels increases
      significantly the contraction, an effect that appears to be mediated by an
      increase in Ca(2+) entry through L-type voltage-dependent Ca(2+) channels.

PMID- 17198917
TI  - Associations of serum uric acid with markers of inflammation, metabolic syndrome,
      and subclinical coronary atherosclerosis.
AB  - BACKGROUND: We examined the associations of serum uric acid (UA) with indices of
      coronary heart disease (CHD) risk, including the 10-year probability of CHD (10y
      CHDr), metabolic syndrome (MS), inflammation (C-reactive protein [CRP] and
      fibrinogen), and the presence and quantity of coronary artery calcium (CAC).
      METHODS: Subjects (n = 1107, mean age 58 years, 59% women) belonged to sibships
      with > or =2 individuals with hypertension diagnosed before age 60 years. UA was
      measured by a colorimetric method, CAC by electron beam computed tomography, and
      CAC score calculated using the method of Agatston. The correlation of UA with 10y
      CHDr, MS components, log CRP, and fibrinogen was assessed after adjustment for
      age and gender. Multivariable regression was used to assess whether UA was
      associated with CAC presence and quantity after (1) adjustment for age and
      gender, and (2) additional adjustment for CHD risk factors. RESULTS: Most
      subjects (71%) had hypertension and 14% had diabetes. Mean (+/- SD) UA level was
      5.97 +/- 1.6 mg/dL, and CAC was detectable in 63% of patients. After adjustment
      for age and gender, UA was significantly correlated with 10y-CHDr, number of MS
      components, log CRP, and fibrinogen. UA was associated with CAC presence and
      quantity after adjustment for age and gender but not after further adjustment for
      systolic blood pressure (BP), diabetes, total and HDL-cholesterol, smoking, and
      body mass index (BMI). CONCLUSIONS: Serum UA was significantly correlated with
      several indices of CHD risk. UA was associated with presence and quantity of CAC,
      but not independently of conventional risk factors.

PMID- 17198918
TI  - Efficacy of indapamide SR compared with enalapril in elderly hypertensive
      patients with type 2 diabetes.
AB  - BACKGROUND: Blood pressure control is the main influential variable in reducing
      microalbuminuria in patients with type 2 diabetes. In this subanalysis of the
      Natrilix SR versus Enalapril Study in hypertensive Type 2 diabetics with
      micrOalbuminuRia (NESTOR) study, we have compared the effectiveness of indapamide
      sustained release (SR) and enalapril in reducing blood pressure and
      microalbuminuria in patients > or =65 years of age. METHODS: Of the 570
      hypertensive patients with type 2 diabetes and persistent microalbuminuria in the
      NESTOR study, 187 (33%) individuals > or =65 years of age were included in this
      analysis. Of these, 95 patients received indapamide SR 1.5 mg and 92 patients
      received enalapril 10 mg, taken once daily in both cases. Adjunctive amlodipine
      and/or atenolol was added if required. RESULTS: The urinary albumin-to-creatinine
      ratio decreased by 46% in the indapamide SR group and 47% in the enalapril group.
      Noninferiority of indapamide SR over enalapril was demonstrated (P = .0236; 35%
      limit of noninferiority) with a ratio of 0.95 (95% CI: 0.68, 1.34). Mean arterial
      pressure decreased by 18 mm Hg and 15 mm Hg in the indapamide SR and the
      enalapril groups, respectively (P = .1136). The effects of both treatments seen
      in these elderly patients were similar to those observed in the main population,
      although the extent of the reduction in microalbuminuria was slightly higher.
      Both treatments were well tolerated, and no difference between groups was
      observed regarding glucose or lipid profiles. CONCLUSION: Indapamide SR is not
      less effective than enalapril in reducing microalbuminuria and blood pressure in
      patients aged >65 years of age with type 2 diabetes and hypertension.

PMID- 17198919
TI  - Raised C-reactive protein and impaired flow-mediated vasodilation precede the
      development of preeclampsia.
AB  - BACKGROUND: The aim of this study was to investigate whether impaired flow
      mediated vasodilation precedes the clinical manifestations of preeclampsia and
      whether is associated with inflammation. METHODS: We conducted a nested case
      control study in a prospective cohort of 506 normotensive women recruited before
      the 30th week of gestation (mean gestational age of 21.8 weeks). At enrollment,
      flow-mediated dilation was measured in the brachial artery using a 7.5-MHz
      transducer. C-reactive protein plasma concentrations and leukocyte count were
      also determined at study entry. Patients were followed until delivery, and
      medical records were reviewed for each patient to confirm the presence or absence
      of preeclampsia or gestational hypertension. RESULTS: Of the women studied, 14
      developed preeclampsia, 18 developed gestational hypertension, and 474 remained
      normotensive. Two normotensive pregnant control subjects were randomly selected
      for each case, matched by maternal age, gestational age, and body mass index at
      enrollment. Women who subsequently developed preeclampsia had lower flow-mediated
      dilation (13.4% +/- 4.3% v 18.2% +/- 7.2, P = .026), higher C-reactive protein
      plasma concentrations (8.7 +/- 5.5 mg/dL v 5.3 +/- 4.3 mg/dL, P = .022) and
      leukocyte count (10.3 +/- 2.0 x 10(9)/L v 9.1 +/- 2.0 x 10(9)/L, P = .036) at
      study entry. CONCLUSIONS: Decreased flow-mediated vasodilation and higher levels
      of CRP are present in early stages of gestation in women who subsequently develop
      preeclampsia. These alterations occur before the onset of clinical symptoms of
      PE. Further studies are needed to confirm that flow-mediated dilation and C
      reactive protein could be useful methods to screen women at risk of developing
      preeclampsia.

PMID- 17198920
TI  - Apparent mineralocorticoid excess manifested in an elderly patient with
      hypothyroidism.
AB  - The syndrome of apparent mineralocorticoid excess (AME) is characterized by
      persistent hypertension and hypokalemia, which is caused by impaired inactivation
      of cortisol (F) to cortisone (E). The thyroid hormone has been known to influence
      the F to E conversion leading to efficacious inactivation of F into E. However,
      there have been no reports regarding the clinical manifestation of secondary AME
      due to hypothyroidism. Here we report an elderly patient who manifested AME,
      showing persistent hypertension with hypokalemia induced by primary
      hypothyroidism. Maintenance of euthyroid conditions ameliorated the concurrent
      AME and restored adrenal secretion of aldosterone after the recovery of the F to
      E shuttle. This case report would broaden our clinical recognition regarding
      acquired AME in relation to thyroid dysfunction.

PMID- 17198922
TI  - Epithelial sodium channel inhibition in cardiovascular disease. A potential role
      for amiloride.
AB  - Amiloride was originally described in 1967 as a potassium-sparing diuretic, the
      mechanism of action of which is to block the epithelial sodium channel (ENaC)
      within the distal tubule of the kidney. In addition, higher doses of amiloride
      were found to be capable of inhibiting the Na(+)/H(+) exchangers (NHE) and the
      Na(+)/Ca(2+) exchangers. In time, several amiloride analogs have been synthesized
      to have a marked increase in their specificity to inhibit the ENaC, the NHE or
      the Na(+)/Ca(2+) exchangers. Although the NHE inhibitors have received the most
      recent attention, large-scale clinical trials using NHE inhibitors in ischemic
      cardiac states have shown them to be either ineffective or associated with an
      unacceptable risk profile. Aldosterone excess in animal models is known to cause
      cardiovascular injury, and blockade of mineralocorticoid receptors in human
      beings with heart disease improves outcomes. However, the exact mechanisms of
      aldosterone injury in animal models of hypertensive disease and protection with
      mineralocorticoid receptor antagonists in human trials of heart failure remain
      unknown. These effects are unexplained by changes in BP, potassium, or sodium
      balance. An additional possibility is that aldosterone action and
      mineralocorticoid receptor blockade is conferred by alterations in ENaC activity.
      Emerging experimental evidence suggests the possibility that systemic or central
      ENaC inhibition or both may be an alternative to the treatment of hypertension
      and cardiovascular disease states. Clinical trials to evaluate further the
      potential beneficial cardiovascular effects of ENaC blockade are needed. This
      article reviews the case for ENaC inhibition as a potential target for
      cardiovascular and renal protection in human beings.

PMID- 17198923
TI  - From kwashiorkor to nephrotic edema.

PMID- 17198925
TI  - Adiponectin and chronic kidney disease.
AB  - Enhanced chronic inflammation and reduced insulin sensitivity are often present
      in chronic kidney disease (CKD). Cardiovascular disease remains a major cause of
      morbidity and mortality in end-stage renal patients. Adiponectin (ADP) is a
      hormone exclusively produced by adipocytes and possesses anti-inflammatory and
      cardioprotective properties. Despite the high prevalence of insulin resistance
      and cardiovascular disease, levels of ADP are increased among end-stage renal
      disease patients on hemo or peritoneal dialysis but also among patients with
      moderate renal failure or with the nephrotic syndrome. Furthermore, lower ADP
      levels are associated with poor cardiovascular outcome. In this review, we
      examine ADP modifications in CKD and discuss the different factors that may have
      an impact on this adipokine metabolism in renal failure.

PMID- 17198924
TI  - Disorders in high-density metabolism with insulin resistance and chronic kidney
      disease.
AB  - Cardiovascular risk increases with each decrement in renal function. Low-density
      lipoprotein (LDL) cholesterol levels are not associated with increased mortality,
      but high-density lipoprotein (HDL) levels are inversely associated with
      cardiovascular risk. Lipoprotein composition with increased abundance of small
      dense LDL and HDL and reduced levels of more buoyant isoforms is similar to what
      is found in states of insulin resistance and in the metabolic syndrome (MS). In
      both cases, high triglyceride levels are associated with reduced HDL levels.
      Chronic kidney disease (CKD) is itself associated with increasing insulin
      resistance as renal function fails. In both instances, decreased levels of apo A
      I and apo A-II are a consequence of increased fractional catabolic rate (FCR),
      resulting from a predominance of small HDL particles. HDL maturation is impaired
      in CKD through decreased activity of lecithin:cholesterol acyltransferase (LCAT),
      and increased cholesterol ester transfer protein (CETP) activity in MS shuttles
      triglycerides back into HDL, thereby destabilizing it. Whether insulin resistance
      is entirely responsible for disorders of HDL metabolism in CKD, or whether the
      process is a result of unrelated pathophysiology, is currently unknown.

PMID- 17198926
TI  - Effects of glucose homeostasis on protein metabolism in patients with advanced
      chronic kidney disease.
AB  - Insulin deficiency is known to be associated with a state of increased muscle
      protein breakdown; this process is mediated by the ubiquitin-proteasome pathway.
      Convincing in vitro data are further supported by extensive studies in humans
      with insulin deprivation and are further substantiated by reversal of muscle
      protein breakdown with insulin treatment. In patients with end-stage renal
      disease (ESRD) and diabetes mellitus (DM), muscle protein breakdown is enhanced
      in both acute and chronic conditions. Recent data also point to the potential
      protein catabolic effects of insulin resistance combined with insulin deficiency.
      Because ESRD is associated with a state of insulin resistance, uremic muscle
      wasting may also be mediated by this pathway.

PMID- 17198927
TI  - Use of single-nucleotide polymorphisms in the search for genetic modifiers of the
      uremic phenotype.
AB  - As the modern nephrology community continues to be burdened with growing numbers
      of patients with end-stage renal disease (ESRD) and exceptionally high mortality
      rates, it is obvious that progress in the development of preventive and
      therapeutic strategies has not been sufficient. This urges nephrologists to focus
      on the underlying mechanisms for ESRD morbidity and mortality, and in particular
      on cardiovascular disease (CVD), which is the major contributor to premature
      death in this patient group. The high prevalence of inflammation, vascular
      ossification, and oxidative stress in ESRD predisposes these patients to CVD.
      Because genetic risk factors may modulate the pathophysiologic response, genotype
      phenotype association studies may provide ways of predicting individual disease
      progression and may shed some light on key regulatory pathways. Indeed, recent
      genetic association studies show that polymorphisms in candidate genes related to
      inflammatory signaling, vascular ossification, and oxidative stress response
      influence the uremic phenotype. DNA polymorphisms may also be used as
      nonconfounded tools in observational studies conducted to test causality, as
      stated by the mendelian randomization approach. To date, the collection of
      genetic data is no longer a limitation because genetic information is easily
      accessible in public databases and high-throughput genotyping technologies are
      available. Advanced bioinformatic tools are now warranted to facilitate the
      integration of accumulating genetic information with clinical and biochemical end
      points and, finally, to implement genotype-phenotype data in the care of patients
      with renal failure to better identify patients at high risk and to design novel
      personalized therapeutic and preventive strategies.

PMID- 17198928
TI  - Advances in carnitine in chronic uremia.
AB  - Carnitine is a conditionally essential metabolite that plays a critical role in
      cell physiology. Carnitine is necessary for fatty acid transport to sites of beta
      oxidation in the mitochondria, where it helps to prevent organic acid
      accumulation. Because of these key regulatory functions, carnitine represents a
      crucial determinant of mitochondrial energy metabolism, whose deficiency may lead
      to metabolic and clinical disturbances. Loss of carnitine through dialytic
      membranes occurs in maintenance hemodialysis, resulting in potential carnitine
      depletion and relative increments of esterified carnitine forms. Carnitine
      supplementation has been shown to counteract such alterations and may be
      associated with clinical benefit. In particular, carnitine supplementation in
      patients on hemodialysis may enhance response to erythropoietin, resulting in
      improved hematologic status. Carnitine was also reported to improve exercise
      tolerance and intradialytic symptoms. Carnitine supplementation may enhance
      insulin resistance, inflammatory and antioxidant status, protein balance, lipid
      profile, and cardiac function. Carnitine administration can be useful for
      selected patients on dialysis who do not adequately respond to standard therapy.

PMID- 17198929
TI  - Thyroid function, endothelium, and inflammation in hemodialyzed patients:
      possible relations?
AB  - OBJECTIVE: Renal function affects the thyroid gland in many ways. Disturbances in
      hemostasis and inflammation are common complications of kidney diseases.
      Endothelial dysfunction may link these two processes. DESIGN AND PATIENTS: A
      cross-sectional study on thyroid hormones in relation to markers of endothelial
      damage and inflammation in 96 hemodialyzed (HD) patients and 39 healthy
      volunteers was performed. SETTING: The study took place in the dialysis unit at a
      university hospital. INTERVENTION: Thyroid hormones, markers of endothelial
      damage (von Willebrand factor, thrombomodulin, intracellular adhesion molecule,
      and CD146), markers of inflammation (high-sensitivity C-reactive protein, tumor
      necrosis factor alpha), other hemostatic parameters (thrombin-antithrombin
      complexes, prothrombin fragments 1 + 2 - F1 + 2, plasmin-antiplasmin complexes,
      tissue plasminogen activator and its inhibitor, tissue factor pathway inhibitor,
      and platelet glycoprotein V) were measured using commercially available kits.
      RESULTS: Free T3 and total T3 were lower in HD patients compared with controls.
      Markers of endothelial dysfunction and inflammation were significantly elevated
      in HD patients compared with controls. In multiple regression analysis T3 was
      independently related to time on dialyses, albumin, iron, ferritin, C-reactive
      protein (CRP), and F1 + 2 in HD patients. Free T3 was also independently related
      to total protein, total calcium, and triglycerides. In patients with CRP less
      than 6 mg/L in multiple regression analysis the only correlates of T3 were
      albumin and ferritin, whereas the only correlates of free T3 were albumin and
      time on dialyses. Multiple regression analysis showed that in HD patients with
      CRP greater than equal to 6 mg/L predictors of free T3 were CRP, F1 + 2, and dose
      of erythropoietin. In healthy volunteers T3 was related to tissue factor pathway
      inhibitor and platelet glycoprotein V was related to thyroid-stimulating hormone.
      CONCLUSIONS: We described novel relations between thyroid hormones and markers of
      endothelial dysfunction and inflammation in HD patients. Thyroid dysfunction is
      related to time on dialyses, endothelial damage, and inflammatory state,
      frequently encountered in uremia. Therefore, the relations between thyroid axis
      and endothelium in HD subjects merit additional studies.

PMID- 17198930
TI  - Impact of kidney bone disease and its management on survival of patients on
      dialysis.
AB  - Despite the enormous cardiovascular disease epidemic and poor survival among
      individuals with chronic kidney disease (CKD), traditional risk factors such as
      hypercholesterolemia, hypertension, and obesity appear not as relevant as was
      previously thought, nor would their management improve survival in patients with
      CKD who are undergoing dialysis. On the contrary, kidney disease wasting (KDW)
      (also known as the malnutrition-inflammation complex), renal anemia, and kidney
      bone disease (KBD) appear to be the 3 most important nontraditional risk factors
      associated with cardiovascular disease in CKD. KBD-associated hyperparathyroidism
      may contribute to worsening refractory anemia and KDW/inflammation. The main
      cause of secondary hyperparathyroidism is active vitamin D deficiency. Hence,
      treatment of patients with KBD with vitamin D analogs, especially those with
      lesser effects on calcium and phosphorus such as paricalcitol, may be the most
      promising option for improving CKD outcomes. By conducting survival analyses in a
      2-year (7/2001 to 6/2003) cohort of 58,058 patients on hemodialysis, we recently
      found that associations between high serum parathyroid hormone and increased
      death risk were masked by the demographic and clinical characteristics of
      patients, and that alkaline phosphatase had an incremental association with
      mortality. Administration of paricalcitol was associated with improved survival
      in time-varying models. We now present additional subgroup analyses that show
      that administration of any dose of paricalcitol, when compared with no
      paricalcitol, is associated with better likelihood of survival in virtually all
      subgroups of patients on hemodialysis. Because these associations may be
      secondary to bias by indication, randomized clinical trials are necessary to
      verify the findings of this and similar observational studies.

PMID- 17198932
TI  - Indoxyl sulfate-lowering capacity of oral sorbents affects the prognosis of
      kidney function and oxidative stress in chronic kidney disease.
AB  - OBJECTIVES: Indoxyl sulfate shows nephrotoxicity and is a stimulating factor for
      progression of chronic kidney disease (CKD). This study was conducted to
      determine (1) whether the indoxyl sulfate-lowering capacity of oral sorbents
      (Kremezin [AST-120], Kureha Corporation, Tokyo, Japan; Merckmezin, Merck Hoei
      Ltd., Osaka, Japan) affects the prognosis of kidney function in CKD, and (2)
      whether oral sorbents reduce the markers of oxidative stress. METHODS: Rats with
      CKD were produced by 4/5 nephrectomy and were randomized into 3 groups: control
      rats, Merckmezin-treated rats, and Kremezin-treated rats. Kremezin and Merckmezin
      were administered to rats at a dose of 4 g/kg with powder chow for 16 weeks,
      whereas powder chow alone was administered to control rats. RESULTS:
      Administration of Kremezin significantly decreased serum and urine levels of
      indoxyl sulfate and serum creatinine and significantly increased creatinine
      clearance as compared with control values. The change in serum indoxyl sulfate
      noted from the initial to the final week showed a positive correlation with the
      change in serum creatinine and a negative correlation with the change in
      creatinine clearance. Kremezin significantly reduced urine levels of acrolein, a
      marker of oxidative stress, as compared with control levels. CONCLUSIONS: The
      indoxyl sulfate-lowering capacity of oral adsorbents affects the prognosis of
      kidney function in CKD. The more serum indoxyl sulfate is reduced, the better
      kidney function is preserved. Kremezin alleviates oxidative stress in the kidneys
      by reducing serum levels of indoxyl sulfate.

PMID- 17198931
TI  - Molecular basis of parathyroid hyperplasia.

PMID- 17198933
TI  - Vascular sources of oxidative stress: implications for uremia-related
      cardiovascular disease.
AB  - Chronic oxidative stress that characterizes uremia has potentially devastating
      effects on the vasculature and has been advocated in the pathogenesis of
      accelerated atherosclerosis in this disease. Recent advances have been made in
      our understanding of the molecular mechanisms that regulate expression and
      activity of key enzymes of vascular oxidative stress (eg, nicotinamide adenine
      dinucleotide phosphate [NAD{P}H] oxidase) and that dissect their interactions
      with signalling pathways of inflammation. The finding that NAD(P)H oxidase is
      upregulated in experimental uremia has important consequences from a physiologic
      and a therapeutic standpoint. In addition, identification of novel proteins
      involved in systemic oxidative stress has shed some new light on the pathogenesis
      of vascular disease. p66(shc) is a cytoplasmic protein that is expressed in a
      wide range of cell types. Initially believed to be involved in signalling
      pathways that regulate cell growth and oxidative stress, it has now been shown to
      play a pivotal role in promoting endothelial dysfunction and atherosclerosis.
      Although a specific role in uremia-related vascular disease has not yet been
      shown, available data in humans suggest involvement of p66(shc) in clinical
      conditions associated with increased oxidative stress.

PMID- 17198934
TI  - Brain activation in uremic anorexia.
AB  - This article reviews current knowledge about mechanisms responsible for uremic
      events, especially those that involve the central nervous system (CNS). Anorexia
      is a frequent complication of the uremic syndrome that contributes to
      malnutrition in patients on dialysis. Uremic anorexia has been associated with
      many factors. Traditionally, anorexia in dialysis patients has been regarded as a
      sign of uremic toxicity; therefore, 2 hypotheses have been proposed: the "middle
      molecule" and "peak concentration" hypotheses; both of these remain unproved.
      Recently, our group has proposed the tryptophan-serotonin hypothesis, which is
      based on a disorder in the amino acid profile that may be acquired when the
      patient is in uremic status. It is characterized by low concentrations of large
      neutral and branched chain amino acids in the cerebrospinal fluid. This situation
      permits a high level of tryptophan transport across the blood-brain barrier and
      enhances the synthesis of serotonin (the final target responsible for inhibiting
      appetite). The role of inflammation in the genesis of anorexia-malnutrition is
      also emphasized. In summary, in the CNS, factors associated with uremic anorexia
      include high levels within the cerebrospinal fluid of proinflammatory cytokines,
      leptin, and free tryptophan and serotonin (hyperserotoninergic-like syndrome),
      along with deficiency of neural nitric oxide (nNO) and disorders in various
      receptors such as melanocortin receptor-4 (MC4-R). Uremic anorexia is a complex
      complication associated with malnutrition and high levels of morbidity and
      mortality. Several uremia-acquired disorders in the CNS such as high
      cerebrospinal fluid levels of anorexigen substances and disorders in appetite
      regulator receptors may explain the lack of appetite.

PMID- 17198935
TI  - The potential role of sterol regulatory element binding protein transcription
      factors in renal injury.
AB  - The disturbed lipid metabolism is a permanent finding in renal failure. It is
      supposed to be a main reason for the accelerated atherosclerosis and high
      cardiovascular and cerebrovascular mortality of patients with renal failure.
      Sterol regulatory element binding proteins (SREBPs) are the transcription factors
      involved in the regulation of lipid homeostasis. They are responsible for the
      transcription activation of genes associated with the synthesis of fatty acids,
      triglycerides, and cholesterol. SREBP-1 gene expression in adipose tissue and
      SREBP-2 in liver are significantly elevated in renal failure. This is accompanied
      with the up-regulation of genes encoding enzymes of both fatty acids and
      cholesterol synthesis and significant serum lipid enhancement. Moreover, it has
      been shown that a destructive accumulation of lipids in the kidney structures is
      associated with enhanced kidney SREBP gene expression and increased lipid
      production. This was found even in the absence of any abnormalities in serum
      lipids. One may suppose that SREBP transcription factors play an important role
      in disturbed lipid metabolism in renal failure.

PMID- 17198936
TI  - Malnutrition is an unusual cause of decreased muscle mass in chronic kidney
      disease.
AB  - Patients with chronic kidney disease (CKD), including those who are treated with
      hemodialysis, frequently develop hypoalbuminemia and a decrease in body weight.
      These abnormalities are usually attributed to malnutrition, but true malnutrition
      (ie, a disorder due to an abnormal diet) is rarely the mechanism causing
      decreased protein stores. Hypoalbuminemia is closely related to evidence of
      inflammation, and a decrease in muscle mass is caused by activation of muscle
      protein breakdown. In uremic rodents and patients, the initial step in the loss
      of muscle protein is activation of caspase-3, which cleaves the complex structure
      of muscle to provide substrates for the ubiquitin-proteasome pathway (UPP). The
      activity of caspase-3 can be detected by the presence of a characteristic 14-kDa
      actin fragment in the insoluble fraction of a muscle biopsy specimen.
      Abnormalities in cell signaling activate caspase-3 and the UPP; a key abnormality
      is decreased activity in the phosphatidylinositol-3-kinase/Akt pathway, leading
      to activation of caspase-3 and a specific E3 ubiquitin conjugating enzyme,
      atrogin-1/MAFbx. Inflammatory cytokines also represent a potential cell signaling
      abnormality that activates muscle protein breakdown, possibly because cytokines
      activate the E3 ubiquigin conjugating enzyme, MuRF1. An understanding of these
      pathways could help the clinician to identify therapeutic targets for preventing
      loss of muscle protein.

PMID- 17198937
TI  - Determinants of serum albumin concentration analyzed in a large cohort of
      patients on maintenance hemodialysis.
AB  - OBJECTIVE: Serum albumin concentration is a powerful predictor of mortality in
      patients on chronic hemodialysis (CHD). This study sought to investigate
      variables associated with serum albumin concentration. DESIGN AND STUDY
      POPULATION: Cross-sectional study in prevalent chronic hemodialysis patients
      treated at the Renal Research Institute between July 1, 2005 and October 31,
      2005. A total of 4,798 (2,199 females) patients were studied. MAIN OUTCOME
      MEASURES: Univariate and multivariate relationships of serum albumin
      concentration with age, sex, race (black, white, other), vascular access type
      (arteriovenous fistula/graft, catheter), white blood cells, neutrophils,
      lymphocytes, equilibrated normalized protein catabolic rate (enPCR), dialysis
      efficacy (eKdrt/V), hemoglobin, phosphate, bio-intact parathyroid hormone
      [bioPTH], creatinine, alanine aminotransferase (ALT), and aspartate
      aminotransferase (AST). RESULTS: Age, access type, and variables of 3 domains,
      namely, nutrition (enPCR; creatinine), eKdrt/V, and inflammation (white blood
      cells; neutrophil:lymphocyte ratio; hemoglobin), were related to serum albumin.
      It is interesting to note that AST was the strongest negative predictor of
      albumin levels. CONCLUSION: In CHD patients, serum albumin concentration is
      defined by a complex interaction of inflammation, nutrition, and dialysis
      efficacy. The relationship between AST and albumin deserves additional study.

PMID- 17198938
TI  - Lipid metabolism in chronic kidney disease: the role of statins in cardiovascular
      risk.
AB  - In the general population, the relation between lipids and cardiovascular disease
      is clearcut, whereas it is highly controversial in chronic kidney disease (CKD)
      patients. This is primarily due to diverging results of retrospective
      observational trials. This study design often encounters confounding, especially
      in renal disease patients. Even if analyses are corrected for multiple
      influences, there might be unknown confounders changing the results. Prospective
      randomized trials assure that groups are comparable except for the intervention
      used. Confounding is eliminated by randomization. Nevertheless, the lipid
      discussion was restarted when two randomized, placebo-controlled, interventional
      trials on lipid-lowering therapy in renal patients have been published
      (Assessment of Lescol in Renal Transplantation and 4D Study [Atorvastatin in
      patients with type 2 diabetes on hemodialysis]). Surprisingly, both showed no
      significant reduction of the primary endpoint by statin therapy. In addition to
      other factors, this might be due to an altered pathogenesis of atherosclerosis in
      renal patients where multiple nontraditional cardiovascular risk factors are to
      be mentioned and different characteristics of cardiovascular disease with a high
      proportion of sudden cardiac death are present. This review will focus on
      dyslipidemia in renal failure and its treatment. The data published so far is
      summarized and grouped according to the different stages of CKD.

PMID- 17198940
TI  - Progressive resistance training and nutrition in renal failure.
AB  - Nutrition and exercise are an integral part of the medical management of many
      chronic and complex conditions. They are interrelated and share many common
      metabolic pathways that may affect disease processes and their management. In
      nephrology, nutritional interventions have been relatively well studied and are
      recommended in many evidence-based clinical practice guidelines for managing
      people with chronic kidney disease (CKD). Over the past 20 years, growing
      evidence has suggested that aerobic exercise interventions are efficacious, and
      that the rationale for progressive resistance training (PRT) is strong,
      particularly in this population, despite a more limited evidence base to date. In
      the small number of clinical trials that have included patients with CKD, PRT
      programs have proved safe, feasible to administer, and efficacious. They have
      been shown to improve clinical, physical, and functional outcomes.

PMID- 17198939
TI  - The role of uric acid in pediatric hypertension.
AB  - Over the past few years, increasing evidence has supported the possible role of
      uric acid as a mediator of high blood pressure. Both animal model data and tissue
      culture experiments suggest that uric acid might cause increased blood pressure
      through a 2-phase process. The first phase is dominated by a uric acid-mediated
      vasoconstriction followed by induction of renal afferent arteriolosclerosis and
      altered pressure natriuresis, leading to sodium-dependent hypertension. We have
      assessed children with newly diagnosed essential hypertension through cross
      sectional studies and clinical trials. Elevated uric acid is closely associated
      with new-onset essential hypertension in children, and preliminary data suggest
      that lowering of uric acid can lower blood pressure in some patients. Future
      studies will be needed to determine whether the mechanisms shown in animal models
      can be extrapolated to children.

PMID- 17198941
TI  - Evaluation of nutritional status in patients with kidney disease: usefulness of
      dietary recall.
AB  - BACKGROUND: Three-day food recall and normalized protein nitrogen appearance
      calculation from pre- and postdialysis plasma urea are the most commonly used
      techniques to assess nutritional intake, but a 7-day dietary recall is probably
      more accurate to approach dietary intake in clinical practice. METHODS: A total
      of 99 hemodialyzed patients from two units were analyzed in a 7-day dietary
      record with a large range of age and without having any signs of malnutrition.
      Dietary protein intake was estimated from the recall and calculated (normalized
      protein catabolic rate) from urea kinetic modeling. Calorie intake and quality
      and repartition of nutrients were estimated from diaries. RESULTS: Repartition of
      nutrients was close to that of a reference population except for a lower glucidic
      contribution (glucide 47%, lipid 36%, protein 16%). Normalized protein catabolic
      rate and dietary protein intake were well correlated (R2 = 0.4), but a large
      variability existed from day to day, according to age (older patients are less
      variable) and day of dialysis (long or short interval). CONCLUSION: A large
      variation in alimentary intake exists from patient to patient and day to day. A 7
      day evaluation of nutrient intake, dialysis adequacy, and nutritional parameters
      seems to be a good solution to guide dietetic counseling.

PMID- 17198942
TI  - Perspectives on the nutritional management of renal disease in Asia: people,
      practice, and programs.
AB  - The high prevalence of end-stage renal disease (ESRD) in many Asian countries is
      attributed to diabetes and hypertension. Health care expenditure in relation to
      per capita income and government share of this expenditure vary among Asian
      countries and are affected by large populations and the poverty factor. The
      impact of ESRD on nutritional management in Asia reveals the need for clinicians
      to balance the requirements for higher standards of dietetic practice as they
      implement optimal care algorithms with the goal of improving outcomes, against
      the backdrop of staffing limitations, limited expertise in renal nutrition
      practice, and cultural diversity among Asian people. This paper discusses current
      aspects of dietetic practice and the likelihood that a change in practice is
      required if dietitians are to play an active role in preventing or slowing down
      ESRD.

PMID- 17198943
TI  - Metabolic and nutritional complications of renal transplantation.
AB  - Renal transplantation is the gold standard therapy for patients with end-stage
      renal disease. However, renal transplantation is associated with various
      metabolic and nutritional complications. This review focuses primarily on factors
      that have a significant impact on cardiovascular disease, namely, hyperlipidemia,
      posttransplant diabetes mellitus, and hyperhomocysteinemia. The prevalence of
      hyperlipidemia in renal transplant patients is estimated at 80% to 90%.
      Corticosteroids, cyclosporine, and sirolimus are commonly associated with
      hyperlipidemia. The incidence of posttransplant diabetes mellitus is estimated to
      be 24% at 36 months post transplant. Glucocorticoids induce metabolic changes
      that result in hyperglycemia. Calcineurin inhibitors have direct islet cell
      toxicity and induced alterations in the transcriptional regulation of insulin.
      Hyperhomocysteinemia is common in renal transplant recipients and is an
      independent risk factor for cardiovascular disease.

PMID- 17198944
TI  - Nutritional supplementation in adult patients on hemodialysis.
AB  - At the beginning of the 1980s, nutritional status appeared as a key element of
      quality of life, health care requirements, and survival during chronic renal
      failure. In patients on dialysis, malnutrition is a major determinant of
      survival, and its management appears to be a key element in terms of outcome.
      Recommendations for the nutritional management of patients on hemodialysis have
      been elaborated by the National Kidney Foundation (NKF) and the European Society
      of Parenteral and Enteral Nutrition (ESPEN).

PMID- 17198947
TI  - A compression force comparison study among three staple fixation systems.
AB  - Traditional staples have recently been redesigned with both new materials and
      engineering techniques to facilitate interfragmentary compression in theory,
      resulting in greater friction between bone fragments to counteract shearing
      forces. In the current study, the biomechanical properties of 3 different staples
      were investigated. The interfacial force at 2 different sites within a calcaneal
      bone model was measured after insertion and activation of the OSStaple, the UNI
      CLIP, and the Smith and Nephew Standard Large Staple after precompression with
      the SYNTHES Small Distractor. Additionally, the ability of each staple to
      maintain compression over a short period of time was investigated. In the current
      bench study, the OSStaple consistently generated the greatest and most uniform
      compression across the bone model osteotomy and was also capable of sustaining
      the compression over the duration of all of the trials.

PMID- 17198946
TI  - Fixation of osteoporotic distal fibula fractures: A biomechanical comparison of
      locking versus conventional plates.
AB  - The increased use of locking plates to treat difficult fracture scenarios has
      been advocated in patients that have reduced bone mineral density. One of these
      difficult fracture patterns, fixation of the distal fragment of a distal fibula
      fracture, may depend on unicortical and cancellous bony purchase. This study
      investigated the construct stiffness afforded by using locking and conventional
      plating schema in a cadaveric model. Overall, the data indicate that a locking
      plate construct with two distal unicortical screws was mechanically equivalent to
      standard plating with 3 distal screws. In addition, fixation with the standard
      plates was dependent on bone mineral density (BMD) whereas the locking plate
      fixation was independent of BMD. The clinical implication of this study is that
      locking plates may be advantageous in patients with the most severe osteoporosis.

PMID- 17198948
TI  - Intermediate results of Buechel Pappas unconstrained uncemented total ankle
      replacement for osteoarthritis.
AB  - We present the functional and radiological results after implantation of thirty
      five uncemented Buechel Pappas total ankle replacements by an independent
      surgeon. All consecutive uncemented Buechel Pappas total ankle replacements were
      performed by the senior author (MSA) between 1990 and 2005. All ankle
      replacements were performed for osteoarthritis. The patients were assessed
      clinically and radiologically. The average follow-up period is five years. Nine
      female patients and 25 male patients with an average age of 69(58-84) were
      enrolled. One patient died before follow-up. Ninety seven percent of patients
      were happy with their operation and ninety seven percent thought it was
      successful. Sixty six percent of patients had no, or occasional pain. All
      patients were mobile and forty five percent of patients required no walking aids.
      Only three percent of patients required two walking aids. The American
      Orthopaedic Foot and Ankle Society Score was 73.3(54-100) at follow-up, compared
      to 34.6(20-56) pre-operatively (p < 0.001). One prosthesis was revised. Two
      fractured medial malleoli occurred and no deep infections were noted. Buechel
      Pappas Uncemented Total Ankle replacement, performed by an independent surgeon,
      can give intermediate results comparable to data published by the designer.
      Patient selection is paramount. Our data compares well with results from other
      uncemented total ankle replacements.

PMID- 17198949
TI  - Components of the Wilson osteotomy that are effective on hallux valgus repair.
AB  - Wilson osteotomy of the first metatarsal is a technically simple and reliable
      operation for the correction of the hallux valgus (HV) deformity. The major
      anatomic components of the osteotomy are the osteotomy angle and the distance of
      the osteotomy to the first metatarsophalangeal (MTP) joint. Lateralization of the
      first metatarsal head is the rationale for correction of the deformity. The main
      disadvantage of the technique is the considerable shortening of the first
      metatarsal. The relation between the amount of HV correction, first metatarsal
      shortening, and the anatomic parameters of the osteotomy was evaluated.
      Radiographs of 46 feet of 32 patients were retrospectively evaluated after an
      average follow-up period of 31.4 months. From the preoperative, early
      postoperative, and last control radiographs, the amount of HV correction, first
      metatarsal shortening, the osteotomy angle, the distance of the osteotomy to the
      first MTP joint, and lateralization of the first metatarsal head were measured.
      The presented study indicated that the osteotomy angle and the lateral
      displacement of the metatarsal head have a significant correlation with the
      amount of HV correction. Distance of the osteotomy to the first MTP joint has no
      relevance with the repair of the deformity. A positive linear correlation was
      present between the osteotomy angle and the first metatarsal shortening. Because
      the amount of first metatarsal shortening has significant influence over the
      clinical result, the main aim in a Wilson osteotomy should be maximum lateral
      displacement of the metatarsal head with a minimum osteotomy angle.

PMID- 17198950
TI  - Tibial intraneural ganglia in the tarsal tunnel: Is there a joint connection?
AB  - Intraneural ganglia are rare entities, and, as such, their pathogenesis has been
      extremely controversial. Recent evidence from intraneural ganglia occurring at
      more proximal sites-the peroneal nerve at the fibular neck (the most common site)
      and the tibial nerve at the knee-has suggested an articular origin rather than de
      novo formation. To our knowledge, of the 10 previous reports of tibial
      intraneural ganglia within the tarsal tunnel by others, a joint connection to the
      ankle joint was only identified in 2 cases. To support a hypothesis that tibial
      intraneural ganglia occurring within the tarsal tunnel region arise from
      neighboring joints, we analyzed 3 patients retrospectively, all of whom had
      magnetic resonance (MR) imaging and operative intervention. One of these patients
      was treated by a peripheral nerve surgeon specializing in foot and ankle surgery.
      The other 2 patients were the only ones previously published in the literature
      who had MR images available for reinterpretation. In none of these cases was a
      joint communication appreciated by radiologists interpreting the MR images
      preoperatively or by surgeons intraoperatively. Our review of these same cases
      demonstrated radiographic evidence of joint communications with the subtalar
      joints. Based on our findings in this article and our knowledge of intraneural
      ganglia occurring at more proximal sites, we believe that tibial intraneural
      ganglia within the tarsal tunnel originate from neighboring joints and that their
      connections to the joints (pedicles) are through articular branches. The
      importance of these connections is 2-fold: first, for their role in the
      pathogenesis of this entity, and second, for their potential therapeutic
      implications. As is highlighted by the clinical and radiographic follow-up in the
      1 patient in this article and in many previously reported at other sites,
      intraneural cyst recurrence can occur if surgeons do not specifically address the
      articular connection.

PMID- 17198951
TI  - The importance of proper shoe gear and safety stirrups in the prevention of
      equestrian foot injuries.
AB  - The aim of this study was to compile specific foot injuries occurring in
      pediatric patients that result from equestrian sports and to highlight the
      importance of wearing adequate riding boots to protect the feet. During a 12-year
      period, 258 children were admitted to Children's Hospital of Geneva for injuries
      resulting from horseback riding. Amongst these children, 8 sustained foot lesions
      that required hospital admission. Four children had compression-type fractures of
      the cuboid (nutcracker fracture of the cuboid) associated with other complex
      midfoot fractures, 2 had Lisfranc fracture dislocations, 1 had a fracture of the
      talus with associated intern malleolar fracture, and the last had a fracture of
      the 5 metatarsals with lateral displacement. All the noted lesions complied with
      the same traumatic mechanisms. The horse fell on the patient, and the child's
      foot, entrapped in the stirrup, was caught in between the animal and the ground.
      The forefoot was bent by indirect violence in abduction by the stirrup, which
      acted as a fulcrum. Serious foot injuries may occur in children during equestrian
      activities. These lesions may be very disabling. Therefore, it is important for
      doctors, instructors, and parents to promote the use of appropriate safety
      equipment, including strengthened riding boots and safety stirrups.

PMID- 17198953
TI  - Severe post-burn hyperextension of metatarsophalangeal joints in a child with
      bilateral foot contracture.
AB  - Achieving a stable plantigrade foot after repair of complex post-burn deformities
      poses a particularly difficult challenge for the foot and ankle surgeon. We
      report an unusual case of a child with severe bilateral forefoot contracture
      deformities treated by soft tissue release and lengthening, and conventional
      wound coverage with split-thickness skin grafting.

PMID- 17198952
TI  - The distally based sural artery flap for ankle and foot coverage.
AB  - The sural artery flap is a distally based fasciocutaneous flap that has many
      advantages to offer for coverage in the foot and ankle area. It has the largest
      arc of rotation of all the regional flaps and does not require sacrifice of any
      major artery, and moderate-to-large-sized defects can be covered adequately. The
      dissection technique is simple, and donor site morbidity is minimal. We report
      our experience with 17 cases. Age range was from 13 to 56 years. Ten (59%)
      defects were posttraumatic, 3 (17%) were related to reconstructive surgery of the
      foot or tendon Achilles', 2 (11%) resulted from tumor resection, and 1 each were
      from infection and gunshot wound. The smallest flap was 6 x 4 cm and the largest
      was 15 x 12 cm, with the average size being 11 x 7.5 cm. In 5 cases, the donor
      site was closed primarily, and in other cases, split-thickness skin graft was
      needed. The short saphenous vein was included in the pedicle in all cases. There
      was no incidence of complete flap necrosis. Follow-up ranged from 3 to 30 months.
      Two cases (12%) developed partial superficial necrosis. In 1 case, there was
      partial wound dehiscence that needed debridement and repair. Another case had
      postoperative discharge, which subsided after removal of the calcaneal plate.
      None of the patients complained of any functional problem related to loss of
      sensation along the lateral border of the foot. The sural island flap is a
      reliable, safe, and easy method of providing soft tissue coverage in the area of
      the foot and ankle.

PMID- 17198954
TI  - Anteromedial subtalar dislocation.
AB  - Subtalar dislocation is the simultaneous dislocation of the distal articulations
      of the talus at both the talocalcaneal and talonavicular joints. It can occur in
      any direction and can always produce significant deformity. The medial
      dislocation is most common. Less common presentations are lateral, anterior, and
      posterior dislocations. These dislocations are associated with osteochondral
      fractures. Closed reduction and immobilization remain the mainstays of treatment.
      Proper radiographs and computed tomography scan confirm the postreduction
      alignment stability of subtalar joints and intraarticular fracture fragments. We
      report a case of anteromedial subtalar dislocation with no osteochondral fracture
      fragments in a 25-year-old man.

PMID- 17198955
TI  - Frontal plane-guided percutaneous tendo Achilles' lengthening.

PMID- 17198957
TI  - Basics of cytology and fluid cytology.
AB  - Cytology as a diagnostic tool has played a major role in the management of
      diseases affecting domestic mammals for over 20 years. It has also become a
      valuable diagnostic tool in the evaluation of nondomestic or the so-called
      "exotic" animal patients, such as small mammals and the lower vertebrates. Common
      cytologic specimens used to evaluate the exotic animal patient include aspirates
      of masses and organs, imprints of biopsy material, tracheal wash samples,
      aspiration of abdominal or coelomic fluid, and fecal smears. In general, the same
      cytologic sample collection and preparation techniques used for domestic mammals
      also apply to exotic animal patients. The interpretation of the cytology specimen
      is generally the same as that of domestic mammals.

PMID- 17198958
TI  - Cytologic diagnosis of diseases of rabbits, guinea pigs, and rodents.
AB  - This article reviews the diseases most amenable to cytologic diagnosis in
      clinical small mammal practice. Diseases of pet rabbits, guinea pigs, rodents,
      chinchillas, sugar gliders, and hedgehogs are addressed. The small size of these
      patients, risk of anesthesia and invasive surgery, and cost factors make small
      mammals ideal patients for cytologic evaluation when applicable; however,
      surprisingly few reports exist in the literature, and no other reviews of
      cytology in these species exist. Much of the data in this article is derived from
      case submissions to Northwest ZooPath, and disease presentations that seem to be
      common in this group of animals are emphasized. Diseases of the skin are
      particularly well represented, especially tumors and inflammatory processes.

PMID- 17198959
TI  - Cytologic diagnosis of diseases of hedgehogs.
AB  - This article focuses on neoplastic diseases because they may be the most frequent
      disease processes in captive hedgehogs according to the literature and authors'
      case files and the most common cases submitted for cytologic diagnosis in these
      species, particularly the African hedgehog (Atelerix albiventris).

PMID- 17198960
TI  - Cytologic diagnosis of diseases of ferrets.
AB  - Cytology is a useful, rapid, inexpensive diagnostic technique that is
      particularly suitable for ferrets because of their small size and readily
      accessible organs and tissues. This article begins with a brief discussion of
      general cytologic information. The remainder of the article concentrates on the
      cytologic features of common diseases that affect ferrets.

PMID- 17198961
TI  - Evaluation of cetacean and sirenian cytologic samples.
AB  - Cytology is a fundamental part of marine mammal veterinary medicine that is
      involved in preventive medicine programs in captive animals and in the health
      assessment of wild populations. Marine mammals often exhibit few clinical signs
      of disease; thus, the cost-effective and widely accessible nature of cytologic
      sampling renders it one of the most important diagnostic procedures with these
      species. Many of these mammals are endangered, protected, and located in
      developing nations in which resources may be scarce. This article can be used as
      a field guide to advise a veterinarian, biologist, or technician working with
      cetaceans or sirenians. A simplistic cost-effective staining technique is used,
      which is ideal for situations in which funds, facilities, or time may be a
      limiting factor in clinical practice.

PMID- 17198962
TI  - Avian cytology.
AB  - An overview of avian cytology is presented, discussing more common abnormalities
      that are encountered in routine clinical practice. The general cytologic features
      of inflammatory, infectious, and neo-plastic lesions are described. The remainder
      of the article covers major cytologic abnormalities by anatomic site of origin of
      the specimens.

PMID- 17198963
TI  - Cytologic diagnosis of diseases in reptiles.
AB  - The cytologic evaluation of samples obtained from reptile patients may provide
      invaluable diagnostic information to the clinician. The following article is
      directed toward providing information regarding the techniques used to obtain
      samples, discussion of sample types, and guidelines for the cytologic
      classification of the materials collected from tissue lesions and body fluids.

PMID- 17198964
TI  - Cytologic diagnosis of disease in amphibians.
AB  - Cytology is an inexpensive yet powerful diagnostic tool that allows for rapid
      diagnosis of many common disease conditions in amphibian patients. Although the
      emphasis of this article is on infectious diseases, there is great potential for
      application of cytologic diagnosis to variety of medical conditions as the
      knowledge base in amphibian medicine and pathology continues to grow. Routine
      methods used that may fall under the umbrella of cytology range from wet mount
      examination of skin scrapings (or gill biopsies of larvae) to examination of
      stained impression smears. Routine Romanowsky's-type stains work well for
      amphibian samples. Preparation of multiple smears is always recommended to allow
      for use of special staining procedures.

PMID- 17198965
TI  - Diagnostic cytology of fish.
AB  - Cytology is an essential part of a diagnostic workup in cases of aquatic animal
      diseases. It is simple to perform, inexpensive, and can yield quick and valuable
      results. External parasites, bacterial and fungal diseases, and gastrointestinal
      infestations are easily determined with wet mount cytology. Because of the
      relatively small number of nonlethal diagnostic techniques available for aquatic
      species, cytologic testing should be considered in every case. Early diagnosis
      can lead to more effective treatment plans, ensuring a better prognostic outcome
      in our patients.

PMID- 17198966
TI  - Cytologic diagnosis of diseases of invertebrates.
AB  - Invertebrate medicine in the context of an exotic or zoo animal veterinary
      practice is in its infancy. Establishment of species-specific reference values
      and evaluation of the effectiveness of cytology for diagnosis of specific
      diseases are necessary. Despite the lack of normal reference parameters for most
      species encountered in clinical practice, important information may be obtained
      from cytologic examination of tissue imprints, aspirates, scrapings, and
      hemolymph. This information may be essential to establish a specific diagnosis,
      focus investigations, and influence treatments. It is hoped that this article
      stimulates veterinarians who work with invertebrates to use diagnostic cytology
      and disseminate the results of their experience.

PMID- 17198967
TI  - Treating HIV in the developing world: getting ahead of the drug development
      curve.

PMID- 17198968
TI  - China's unique position in discovery and preclinical research.

PMID- 17198969
TI  - Enantioselective organocatalysis.
AB  - Enantioselective organocatalysis has emerged as a powerful synthetic paradigm
      that is complementary to metal-catalysed transformations and has accelerated the
      development of new methods to make diverse chiral molecules. The operational
      simplicity, ready availability of catalysts and low toxicity associated with
      organocatalysis makes it an attractive method to synthesise complex structures.
      Here, we discuss the impact of enamine, iminium, nucleophilic and Bronsted acid
      catalysts in organic synthesis, and highlight key strategic methods to assemble
      useful molecules with high enantiomeric purity.

PMID- 17198970
TI  - Drug-target identification in Drosophila cells: combining high-throughout RNAi
      and small-molecule screens.
AB  - RNA interference (RNAi) and small-molecule approaches are synergistic on multiple
      levels, from technology and high-throughput screen development to target
      identification and functional studies. Here, we describe the RNAi screening
      platform that we have established and made available to the community through the
      Drosophila RNAi Screening Center at Harvard Medical School. We then illustrate
      how the combination of RNAi and small-molecule HTS can lead to effective
      identification of targets in drug discovery.

PMID- 17198971
TI  - Multi-target therapeutics: when the whole is greater than the sum of the parts.
AB  - Drugs designed to act against individual molecular targets cannot usually combat
      multigenic diseases such as cancer, or diseases that affect multiple tissues or
      cell types such as diabetes and immunoinflammatory disorders. Combination drugs
      that impact multiple targets simultaneously are better at controlling complex
      disease systems, are less prone to drug resistance and are the standard of care
      in many important therapeutic areas. The combination drugs currently employed are
      primarily of rational design, but the increased efficacy they provide justifies
      in vitro discovery efforts for identifying novel multi-target mechanisms. In this
      review, we discuss the biological rationale for combination therapeutics, review
      some existing combination drugs and present a systematic approach to identify
      interactions between molecular pathways that could be leveraged for therapeutic
      benefit.

PMID- 17198972
TI  - Data reduction and representation in drug discovery.
AB  - Pre-clinical drug discovery relies increasingly on huge volumes of inter-related
      multivariate data. To make sense of these data and enable quality decision-making
      based on this plethora of information they must be presented in an interpretable
      form. Reducing the dimensionality of the data often leaves a data set that is too
      complex to interpret readily, so intuitive visualization methods are needed.
      Bioinformatics has provided much of the impetus for visualizing complex data, the
      cheminformatics community has been aggressive with the data-reduction problem.
      The increasing appreciation of the inter-related multifactorial nature of pre
      clinical drug discovery makes visualization a burgeoning and active field that
      spans biosciences, mathematics and visual psychology.

PMID- 17198973
TI  - Blood-brain barrier delivery.
AB  - Neuropharmaceutics is the largest potential growth sector of the pharmaceutical
      industry. However, this growth is blocked by the problem of the blood-brain
      barrier (BBB). Essentially 100% of large-molecule drugs and >98% of small
      molecule drugs do not cross the BBB. The BBB can be traversed because there are
      multiple endogenous transporters within this barrier. Therefore, brain drug
      development programs of the future need to be re-configured so that drugs are
      formulated to enable transport into the brain via endogenous BBB transporters.

PMID- 17198974
TI  - Outsourcing lead optimization: constant change is here to stay.
AB  - Since last reviewed in 2004, the market for outsourcing lead optimization has
      continued to grow and to change. Here, I review some of the key events that have
      taken place in this time, particularly merger and acquisition activity, and also
      seek to delineate some of the emerging trends. Of special note are the rise of
      low-cost companies providing contract services in Eastern Europe and Asia, and
      the varying responses to this trend by established companies in Western Europe
      and the USA. Overall, the marketplace remains highly competitive and dynamic and,
      as such, is a challenging and exciting place in which to conduct business.

PMID- 17198975
TI  - Drugs in other drugs: a new look at drugs as fragments.
AB  - The authors of this review have examined the complete set of marketed drugs, with
      regards to looking for structural similarities between drugs. By comparing the
      structures of all drugs, it has been established how many times one marketed drug
      occurred as a substructure within another marketed drug. A total of 209 from 1386
      marketed drugs sized between 100 and 1500 Da (i.e. 15% of the 1386 total) are
      contained within other drugs, differing by one or more continuous chemical
      fragment, and as many as 418 drugs from the total of 1386 (i.e. 30%) contain
      other drugs as substructure fragments. Many smaller drugs occur in multiple
      larger drugs. Most of the small changes tend to retain primary indicated
      pharmacology, whereas larger changes more often lead to different primary
      pharmacology. We identify a subset of drugs that can be used in fragment-based
      drug discovery strategies. In addition, the analysis enhances understanding of
      marketed drug space from the chemical building-block perspective.

PMID- 17198976
TI  - Current and future drugs targeting one class of innate immunity receptors: the
      Toll-like receptors.
AB  - Innate immunity receptors are germline-encoded receptors that can sense molecular
      signatures of pathogens and cancer cells. Recent advances in immunology
      demonstrate the key role of these receptors in inflammation and initiation of
      subsequent immune responses, including adaptive immunity. Pharmaceutical interest
      in this field has grown with the retrospective demonstration that some marketed
      drugs targeting cancer or infectious diseases act via those receptors. In this
      review, I present an update on the scientific rationale for targeting one class
      of innate immunity receptor, the Toll-like receptors, and an update on the
      development status of corresponding drug candidates in infectious diseases,
      cancer, allergy and vaccines.

PMID- 17198977
TI  - Pharmacological targeting of lysine acetyltransferases in human disease: a
      progress report.
AB  - Lysine acetyltransferases (LATs) are a structurally disparate group of enzymes
      involved in regulating transcription by participating as cofactors in
      transcriptional regulatory complexes, and by acetylation of lysine residues in
      histones and other proteins. Aberrant LAT function probably plays an important
      part in the pathogenesis of certain cancers, especially leukaemias and endocrine
      tumours. However, LAT activity might also be an important drug target in a range
      of other indications, including inflammatory lung diseases, viral infections and
      metabolic disorders. At present, comparatively few LAT inhibitors are known, but
      progress regarding the understanding of their structural and functional biology
      is now beginning to reveal LATs as promising new epigenetic drug targets.

PMID- 17198980
TI  - Potential interference of small neodymium magnets with cardiac pacemakers and
      implantable cardioverter-defibrillators.
AB  - BACKGROUND: Magnetic fields may interfere with the function of cardiac pacemakers
      and implantable cardioverter-defibrillators (ICDs). Neodymium-iron-boron (NdFeB)
      magnets, which are small in size but produce strong magnetic fields, have become
      widely available in recent years. Therefore, NdFeB magnets may be associated with
      an emerging risk of device interference. OBJECTIVE: We conducted a clinical study
      to evaluate the potential of small NdFeB magnets to interfere with cardiac
      pacemakers and ICDs. METHODS: The effect of four NdFeB magnets (two spherical
      magnets 8 and 10 mm in diameter, a necklace made of 45 spherical magnets, and a
      magnetic name tag) was tested in forty-one ambulatory patients with a pacemaker
      and 29 patients with an ICD. The maximum distance at which the magnetic switch of
      a device was influenced was observed. RESULTS: Magnetic interference was observed
      in all patients. The maximum distance resulting in device interference was 3 cm.
      No significant differences were found with respect to device manufacturer and
      device types. CONCLUSION: Small NdFeB magnets may cause interference with cardiac
      pacemakers and ICDs. Patients should be cautioned about the interference risk
      associated with NdFeB magnets during daily life.

PMID- 17198981
TI  - Magnet decoration, beautiful but potentially dangerous for patients with
      implantable pacemakers or defibrillators.

PMID- 17198983
TI  - Entrapment of circular mapping catheter in the mitral valve.
AB  - BACKGROUND: Ablation procedures in the left atrium for treatment of atrial
      fibrillation are becoming increasingly common. The procedure often involves
      placing one or two circular mapping catheters in the left atrium. Entrapment of
      an ablation catheter in the mitral valve during ablations of left-sided accessory
      pathways by the retrograde approach has been described in two earlier published
      reports. More recently, several reports describe similar entrapment of a mapping
      catheter. In a recently published review, however, only one case of unspecified
      valve damage was registered among 8745 atrial fibrillation procedures. OBJECTIVE:
      The purpose of this study was to evaluate patients with entrapment. METHODS:
      Retrospective analysis of electrophysiological results. RESULTS: We describe
      three patients with entrapment during ablations for atrial fibrillation. The
      entrapments occurred with three different operators at three different
      electrophysiological laboratories within 2 years. The complication described here
      may be more common than is widely appreciated. CONCLUSIONS: From our figures, we
      estimate the incidence of the complication to 0.9% (95% confidence interval, 0.2
      2.5%).

PMID- 17198982
TI  - Idiopathic ventricular arrhythmias originating from the tricuspid annulus:
      Prevalence, electrocardiographic characteristics, and results of radiofrequency
      catheter ablation.
AB  - BACKGROUND: Idiopathic ventricular tachycardias (VTs) and premature ventricular
      contractions (PVCs) arising from the tricuspid annulus have been reported.
      OBJECTIVE: The purpose of this study was to clarify the prevalence and
      characteristics of VT/PVCs originating from the tricuspid annulus. METHODS: The
      ECG characteristics and results of radiofrequency (RF) catheter ablation were
      analyzed in 454 patients with idiopathic VT/PVCs. RESULTS: Thirty-eight (8%)
      patients had VT/PVCs arising from the tricuspid annulus: 28 VT/PVCs (74%)
      originated from the septal portion of the tricuspid annulus and the remaining 10
      (26%) from the free wall of the tricuspid annulus. QRS duration and Q-wave
      amplitude in each of leads V1-V3 were greater in VT/PVCs arising from the free
      wall of the tricuspid annulus than those from the septum of the tricuspid annulus
      (all P < .01). "Notching" of the QRS complex was observed more often in VT/PVCs
      arising from the free wall of the tricuspid annulus than those from the septum of
      the tricuspid annulus (P < .01). A Q wave in lead V1 was observed more often in
      VT/PVCs arising from the septum of the tricuspid annulus than those from the free
      wall of the tricuspid annulus (P < .005). R-wave transition occurred beyond lead
      V3 more often in VT/PVCs arising from the free wall of the tricuspid annulus than
      those from the septum of the tricuspid annulus (P < .005). RF catheter ablation
      eliminated 90% of the VT/PVCs arising from the free wall of the tricuspid annulus
      but only 57% of the VT/PVCs arising from septum of the tricuspid annulus.
      CONCLUSION: Idiopathic VT/PVCs arising from tricuspid annulus are not rare, and
      the detailed origin can be determined by ECG analysis. The preferential site of
      origin was the septum but also could be the free wall of the tricuspid annulus.

PMID- 17198984
TI  - The effects of rate and irregularity on sympathetic nerve activity in human
      subjects.
AB  - BACKGROUND: We have recently shown that atrial fibrillation is associated with an
      increase in sympathetic nerve activity (SNA) compared with sinus rhythm. It
      remains unclear, however, whether these findings are true at various rates and
      whether the magnitude of sympathoexcitation is related to the degree of
      irregularity. OBJECTIVE: To determine the role of irregularity in mediating the
      SNA changes at various pacing rates. Univariate analysis showed that as the
      irregularity increased, SBP increased (r = 0.44, P < .001) but that MAP and DBP
      did not change significantly. METHODS: Using custom-made software,
      atrioventricular sequential pacing with predetermined rates (100, 120, and 140
      bpm) and irregularities (standard deviation = 0%, 5%, 15%, and 25% of mean cycle
      length) was performed in 23 patients referred for electrophysiologic evaluation.
      Pacing at each rate/irregularity was performed for 2 minutes, with 2 minutes of
      recovery in between. Systolic, diastolic, and mean arterial blood pressure (SBP,
      DBP, and MAP), central venous pressure (CVP), and SNA were measured at baseline
      and during pacing. RESULTS: Univariate analysis showed that as the irregularity
      increased, SBP increased (r = 0.44, P < .001 but that MAP and DBP did not change
      significantly. A significant correlation was found between the pacing
      irregularity and SNA, with greater sympathoexcitation noted at greater degrees of
      irregularity (r = 0.2, P = .04). A five-variable linear model using DBP, MAP,
      CVP, and degree of pacing irregularity to predict SNA was highly statistically
      significant (r = 0.46, P < .001). After controlling for hemodynamic changes, for
      every 1% increase in irregularity, there was a 6.1% increase in SNA. CONCLUSION:
      We have shown that greater degrees of irregularity cause greater
      sympathoexcitation and that the effects of irregular pacing on SNA are
      independent of the hemodynamic changes.

PMID- 17198985
TI  - Seasonal variation in paroxysmal atrial fibrillation documented by 24-hour Holter
      electrocardiogram.
AB  - BACKGROUND: The incidence of various cardiovascular diseases is known to exhibit
      seasonal variations, but seasonal patterns of paroxysmal atrial fibrillation (AF)
      have not been well characterized. OBJECTIVE: The objective of this study was to
      determine whether seasonal variation affects the incidence of paroxysmal AF and
      whether this pattern is affected by patient age. METHODS: We identified 258
      paroxysmal AF episodes in 237 patients (age 65 +/- 14 years, mean +/- standard
      deviation; age range 16-95 years) among 12,390 consecutive 24-hour Holter
      electrocardiogram recordings obtained from 2001 to 2005 at our institute.
      Seasonal variations were analyzed by both month and by season. The relative risk
      (RR) of AF for each period was determined as being high or low in relation to the
      overall mean incidence. The association among clinical covariates and risk of
      paroxysmal AF was tested by logistic regression analysis. RESULTS: The incidence
      of paroxysmal AF was highest in September (RR = 1.40, 95% confidence interval
      [CI] 1.36-1.44) and lowest in June (RR = 0.52, 95% CI 0.50-0.54), with an RR
      difference of 63% (P < .001) among all patients. Patients aged > or =65 years
      demonstrated a peak incidence in September (RR = 1.46, 95% CI 1.41-1.51) and a
      minimum in June (RR = 0.55, 95% CI 0.52-0.58), while those aged <65 years showed
      a peak incidence in December (RR = 1.33, 95% CI 1.27-1.39) and a minimum in June
      (RR = 0.49, 95% CI 0.45-0.53). The incidence of paroxysmal AF also showed an
      autumn peak (RR = 1.21, 95% CI 1.16-1.27) and a summer minimum (RR = 0.66, 95% CI
      0.62-0.70), with an RR difference of 53% (P < .001) among all patients. This
      seasonal variation in paroxysmal AF did not differ between patients of different
      age ranges. Clinical covariates including underlying disease or medications did
      not influence the monthly or seasonal variation in paroxysmal AF. There was a
      significant inverse relationship between the incidence of paroxysmal AF and the
      length of daylight in patients aged <65 years (r = -0.57, P < .05). CONCLUSION:
      There was a significant seasonal variation in paroxysmal AF, with maximum and
      minimum incidences in autumn and summer, respectively, and this pattern was not
      age dependent.

PMID- 17198986
TI  - Right septal macroreentrant tachycardia late after mitral valve repair:
      Importance of surgical access approach.
AB  - BACKGROUND: Reentrant atrial tachycardias may occur after mitral valve surgery.
      These usually involve the left atrium or the lateral wall of the right atrium
      around the atriotomy scar. OBJECTIVE: The purpose of this study was to test
      whether ablation could eliminate atrial tachycardia after mitral valve repair.
      METHODS: Three patients (two men, one woman; mean age 57 +/- 12 years) were
      studied 48 +/- 38 months after mitral valve repair. In all cases, the surgical
      approach involved a transseptal incision. Tachycardia mapping was performed using
      multipolar catheters and the three-dimensional electroanatomic mapping system.
      The mean flutter cycle length was 313 +/- 21 ms. All patients had dual-loop
      reentry with one circuit around a septal scar and the other circuit around the
      tricuspid annulus. RESULTS: Successful radiofrequency ablation of the septal
      circuit was performed between the scar and the superior tricuspid annulus in all
      three cases. CONCLUSION: After mitral valve repair using a transseptal incision,
      dual-loop reentry may occur around the septal scar and the tricuspid annulus.
      Successful ablation may be achieved with an ablation line between the scar and
      the tricuspid annulus.

PMID- 17198987
TI  - Three-dimensional rotational angiography of the left atrium and esophagus--A
      virtual computed tomography scan in the electrophysiology lab?
AB  - BACKGROUND: Three-dimensional (3D) reconstruction of the heart and surrounding
      structures has been supplementing traditional two-dimensional imaging to guide
      diagnostic and therapeutic electrophysiologic procedures. Current methods using
      computed tomography (CT)/magnetic resonance imaging (MRI) reconstruction have
      certain limitations. OBJECTIVE: We investigated the feasibility of rotational
      angiography (RA) combined with simultaneous esophagogram to create an
      intraprocedural 3D reconstruction of the left atrium (LA) and the esophagus.
      METHODS: Rotational angiography was performed. Contrast was injected via a
      pigtail catheter positioned in the left or right pulmonary artery to achieve a
      levophase venous cycle opacification of the ipsilateral pulmonary veins and
      adjacent LA. Simultaneous administration of oral contrast allowed a 3D
      reconstruction of the esophagus in the same image. Qualitative and quantitative
      comparison between the intraprocedural 3D RA and a remote CT scan was performed
      in 11 consecutive patients undergoing ablation for atrial fibrillation. RESULTS:
      Adequate visualization of the pulmonary veins, adjacent posterior LA, and
      esophagus was achieved in 10 patients. Determination of pulmonary transit time to
      guide the initiation of RA resulted in better-quality imaging. A close
      correlation between 3D RA and CT was found. Based on close proximity between the
      LA and esophagus, the ablation procedure was modified in three patients.
      CONCLUSIONS: Three-dimensional RA of the LA and esophagus is a promising new
      method allowing intraprocedural 3D reconstruction of these structures comparable
      in quality to a CT scan. Further studies refining the method are justified
      because it could eliminate the need for CT/MRI scans before ablation.

PMID- 17198988
TI  - Rotational angiography: A novel application of an old concept.

PMID- 17198990
TI  - Just another Brugada syndrome mutation?

PMID- 17198989
TI  - A sodium channel pore mutation causing Brugada syndrome.
AB  - BACKGROUND: Brugada and long QT type 3 syndromes are linked to sodium channel
      mutations and clinically cause arrhythmias that lead to sudden death. We have
      identified a novel threonine-to-isoleucine missense mutation at position 353
      (T353I) adjacent to the pore-lining region of domain I of the cardiac sodium
      channel (SCN5A) in a family with Brugada syndrome. Both male and female carriers
      are symptomatic at young ages, have typical Brugada-type electrocardiogram
      changes, and have relatively normal corrected QT intervals. OBJECTIVES: To
      characterize the properties of the newly identified cardiac sodium channel
      (SCN5A) mutation at the cellular level. RESULTS: Using whole-cell voltage clamp,
      we found that heterologous expression of SCN5A containing the T353I mutation
      resulted in 74% +/- 6% less peak macroscopic sodium current when compared with
      wild-type channels. A construct of the T353I mutant channel fused with green
      fluorescent protein failed to traffic properly to the sarcolemma, with a large
      proportion of channels sequestered intracellularly. Overnight exposure to 0.1 mM
      mexiletine, a Na(+) channel blocking agent, increased T353I channel trafficking
      to the membrane to near normal levels, but the mutant channels showed a
      significant late current that was 1.6% +/- 0.2% of peak sodium current at 200 ms,
      a finding seen with long QT mutations. CONCLUSIONS: The clinical presentation of
      patients carrying the T353I mutation is that of Brugada syndrome and could be
      explained by a cardiac Na(+) channel trafficking defect. However, when the defect
      was ameliorated, the mutated channels had biophysical properties consistent with
      long QT syndrome. The lack of phenotypic changes associated with the long QT
      syndrome could be explained by a T353I-induced trafficking defect reducing the
      number of mutant channels with persistent currents present at the sarcolemma.

PMID- 17198991
TI  - Interactive atrial neural network: Determining the connections between
      ganglionated plexi.
AB  - BACKGROUND: The electrophysiologic functions of the intrinsic cardiac autonomic
      nervous system (ANS) are not well understood. OBJECTIVES: The purpose of this
      study was to investigate the functional interactions between ganglionated plexi
      within the intrinsic cardiac ANS. METHODS: The hearts of 21 dogs were exposed via
      right and/or left thoracotomy to expose the (1) anterior right ganglionated plexi
      near the caudal end of the sinoatrial node, (2) inferior right ganglionated plexi
      at the junction of inferior vena cava and atria, and (3) superior left
      ganglionated plexi near the junction of left superior pulmonary vein and left
      pulmonary artery. Ganglionated plexi were stimulated at 0.6 to 8.0 V (square
      waves, 20 Hz, 0.1-ms duration). Sinus rate, AH interval during atrial pacing, and
      ventricular rate during atrial fibrillation were compared before and after
      ganglionated plexi stimulation and after their ablation. RESULTS: Anterior right
      ganglionated plexi stimulation induced significant AH prolongation and slowing of
      ventricular rate and sinus rate. When inferior right ganglionated plexi was
      ablated, slowing of sinus rate by anterior right ganglionated plexi stimulation
      was unaltered, but inhibition of AV conduction was eliminated. Superior left
      ganglionated plexi stimulation induced similar effects on sinus and AV nodal
      function, and sinus rate slowing was markedly attenuated by anterior right
      ganglionated plexi ablation. Ablation of both anterior right ganglionated plexi
      and inferior right ganglionated plexi eliminated AV conduction inhibition but not
      sinus rate slowing by superior left ganglionated plexi stimulation. CONCLUSION:
      This study provides functional evidence for the interconnections between
      ganglionated plexi to modulate sinus and AV nodal function, supporting clinical
      evidence that interconnections within the intrinsic cardiac ANS are critical
      elements in identifying the targets for atrial fibrillation ablation.

PMID- 17198992
TI  - The atrial neural network: Ablation minefield or strategic target?

PMID- 17198993
TI  - Differences in arrhythmogenicity between the canine right ventricular outflow
      tract and anteroinferior right ventricle in a model of Brugada syndrome.
AB  - BACKGROUND: The Brugada syndrome is characterized by ST-segment elevation on the
      ECG, especially in the right precordial leads sensitive to the right ventricular
      outflow tract (RVOT). OBJECTIVES: The purpose of this study was to evaluate the
      hypothesis that right ventricular electrophysiologic heterogeneity caused
      arrhythmogenicity in the Brugada syndrome. METHODS: Action potentials (APs) were
      mapped on the epicardium of 14 RVOT preparations and on the transmural surfaces
      of 15 pairs of RVOT and right ventricular anteroinferior (RVAI) preparations
      isolated from canine hearts. Brugada ECG and arrhythmias were induced with
      pilsicainide (2.5-12.5 micromol/L), pinacidil (1.25-12.5 micromol/L), and
      terfenadine (2.0 micromol/L). RESULTS: Low doses of drugs elevated the J-ST
      segment and induced APs with both short and long action potential durations
      (APDs) in contiguous RVOT epicardial regions. In addition, APs in the RVOT had a
      larger phase 1 notch and longer APD than in RVAI. The longest APDs were in the
      epicardium in RVOT but in the endocardium in RVAI regions. High doses of drugs
      eliminated the phase 2 dome of the AP and abbreviated APDs in the epicardium but
      not in endocardium and reduced the epicardial heterogeneity of APs but increased
      the transmural gradient of APD in 14 (93%) of the RVOT preparations. In contrast,
      abbreviations of epicardial APDs occurred in only 4 (27%) of the RVAI
      preparations. Ventricular tachycardia occurred more frequently in the RVOT (47%)
      than in paired RVAI preparations (7%). Blocking the transient outward current
      reduced the heterogeneity of APs and eliminated arrhythmogenicity in all
      preparations. CONCLUSION: Compared with the RVAI region, the RVOT has greater
      electrophysiologic heterogeneity that contributes to arrhythmogenicity in this
      model of Brugada syndrome.

PMID- 17198994
TI  - Calculation of effective VV interval facilitates optimization of AV delay and VV
      interval in cardiac resynchronization therapy.
AB  - BACKGROUND: In hearts with left bundle branch block (LBBB), both atrioventricular
      (AV) delay and interventricular (VV) interval determine left ventricular (LV)
      pump function in cardiac resynchronization therapy (CRT). The optimal combination
      of AV delay and VV interval currently is determined by extensive hemodynamic
      testing. OBJECTIVES: The purpose of this study was to investigate whether the
      effective VV interval (VV(eff)) can be used to optimize AV delay and VV interval.
      METHODS: In eight canine hearts with chronic LBBB, LV pacing was performed at
      various AV delays as well as biventricular pacing at multiple AV delays and VV
      intervals. LV pump function was assessed from LVdP/dt(max) and stroke volume
      (conductance catheter). Interventricular asynchrony was calculated from the
      timing difference between upslope of LV and RV pressure curves. VV(eff) was
      defined as the time delay between activation of the RV apex and LV lateral wall,
      irrespective of the source of RV activation (RV pacing or intrinsic conduction).
      VV(eff) was determined from pacemaker settings and surface ECGs recorded during
      biventricular pacing at various AV delays (positive values denote LV
      preexcitation). RESULTS: For all animals, the relationship between VV(eff) and
      LVdP/dt(max) as well as LV stroke work was parabolic. Maximal improvement in
      LVdP/dt(max) was similar during LV pacing, simultaneous biventricular pacing, and
      sequential biventricular pacing and was obtained at similar values of VV(eff).
      VV(eff) was strongly correlated with interventricular asynchrony (R = 0.97 +/-
      0.03). Optimum LVdP/dt(max) occurred at VV(eff) ranging from -24 to 12 ms (mean 
      6 +/- 13 ms). For each experiment, the optimal VV(eff) was virtually equal to the
      value halfway between its minimum (during LV pacing at short AV delay) and
      maximum (during LBBB) value (R = 0.91). CONCLUSION: Use of VV(eff) facilitates
      determination of the best combination of AV delay and VV interval during
      biventricular pacing. For each individual heart, VV(eff), resulting in optimum LV
      pump function, can be estimated using surface ECGs recorded during biventricular
      pacing.

PMID- 17198995
TI  - Will better understanding of the mechanisms of cardiac resynchronization
      streamline programming?

PMID- 17198996
TI  - Elimination of left superior pulmonary vein ostial potentials during
      radiofrequency ablation at the mitral isthmus.

PMID- 17198997
TI  - Incessant ventricular tachycardia in fulminant lymphocytic myocarditis: Evidence
      for origin in the Purkinje system and successful treatment with ablation.

PMID- 17198998
TI  - Tako-Tsubo cardiomyopathy after radiofrequency ablation of atrioventricular nodal
      reentrant tachycardia.

PMID- 17198999
TI  - A novel method for preventing phrenic nerve injury during catheter ablation.

PMID- 17199000
TI  - Where are we, and where are we heading in the device management of ventricular
      tachycardia/ventricular fibrillation?

PMID- 17199001
TI  - Change in H-H' interval during intrahisian block: What is the mechanism?

PMID- 17199003
TI  - How to recognize, manage, and prevent complications during atrial fibrillation
      ablation.

PMID- 17199002
TI  - Implantable cardioverter-defibrillator malfunction with out-of-range lead
      measurements: What is the cause?

PMID- 17199004
TI  - Reversible exercise-induced advanced atrioventricular block due to cardiac
      sarcoidosis.

PMID- 17199005
TI  - Highly respected and experienced team of investigators used in canine hearts a
      multiterminal 208 electrode grid with 0.5 mm interelectrode spacing for recording
      epicardial electrograms, and paired those electrograms against a single KCl
      electrode at a separate site.

PMID- 17199006
TI  - A nice case of swallowing-induced atrial tachycardia with successful
      radiofrequency ablation of an ectopic focus in right atrium.

PMID- 17199007
TI  - Significant correlation between monophasic action potential (MAP) durations and
      activation-recovery intervals (ARIs) determined at the maximum positive slope of
      the positive T wave (conventional method).

PMID- 17199010
TI  - The role of the Heart Rhythm Society in integrating the healthcare enterprise.

PMID- 17199012
TI  - New antiepileptic drugs--discovery, development, and update.

PMID- 17199013
TI  - Currently available antiepileptic drugs.
AB  - Many new antiepileptic drugs (AEDs) have become available over the past 15 years.
      At the same time, the emphasis on treating patients with epilepsy has grown from
      stopping seizures to avoiding side effects and maximizing quality of life. This
      review summarizes currently available AEDs, and presents general treatment
      principles and guidelines for AED selection. Unfortunately, despite the increased
      treatment options of today, seizure freedom without side effects remains
      unattainable for too many patients with epilepsy. Consequently, there remains a
      significant need for further development of new therapies.

PMID- 17199014
TI  - Discovery of antiepileptic drugs.
AB  - Since 1993, the Anticonvulsant Drug Development Program has contributed to the
      successful development of nine clinically effective drugs for the symptomatic
      treatment of epilepsy. These include felbamate (1993), gabapentin (1994),
      lamotrigine (1994), fosphenytoin (1996), topiramate (1996), tiagabine (1997),
      levetiracetam (1999), zonisamide (2000), and oxcarbazepine (2000). Despite the
      apparent success of the current discovery process, a significant need persists
      for more efficacious and less toxic antiepileptic drugs (AEDs). This is
      particularly true for patients whose seizures remain refractory to the currently
      available AEDs. This chapter will review the current process for AED discovery
      employed by the Anticonvulsant Drug Development Program at the University of Utah
      and other laboratories working toward the common goal of discovering better
      therapeutic options for patients living with epilepsy. It will discuss some of
      the inherent advantages and limitations of the primary animal models employed,
      while offering insight into potential future directions as we seek to better
      understand the pathophysiology underlying acquired epilepsy, therapy resistance,
      and epileptogenesis.

PMID- 17199016
TI  - Clinical development of antiepileptic drugs in adults.
AB  - Over the last two decades, ten so-called newer antiepileptic drugs (AEDs) have
      been approved around the world, the majority of which have found and maintained a
      place in the seizure-fighting armamentarium for the whole spectrum of epilepsies
      and epileptic syndromes; some of these drugs have features that are improved
      compared with the older drugs. Within that same time period, the process of
      clinical development of AEDs has also undergone changes and has become much more
      complex and costly. Efforts are underway to shift decision-making about the
      clinical viability of AED candidates to earlier development stages, using the
      concept of translational medicine. However, thus far all of the newer AEDs have
      undergone a standard development as an adjunct in the control of adult partial
      seizures; in some cases, development has been expanded to other seizure types and
      pediatric syndromes. Currently, the path to global approval for use in
      monotherapy is under review and is often debated with regulatory authorities.
      Clinical treatment guidelines consider randomized, blinded, well controlled
      studies as the premier level of evidence-based medicine; these studies originate
      mostly in confirmatory phases of the development program. However, with the rigid
      designs and criteria in regulatory driven trials, effectiveness in the clinical
      practice setting may not be sufficiently predicted by these studies, leading to
      frustrations from individual practitioners. Finally, additional safety issues
      regularly occur only after the postlaunch exposure to a broader population making
      necessary a continuing, and thorough, pharmacovigilance after the AED has come to
      market.

PMID- 17199017
TI  - Clinical development of antiepileptic drugs for children.
AB  - A clinical development plan specific to children is a necessary component of
      every development plan for a new antiepileptic drug (AED). In the last decade,
      considerable discussion has occurred in the medical and regulatory communities,
      resulting in specific pediatric drug development legislation. Ethical issues are
      a foremost consideration in the design and conduct of studies. The timing of
      clinical studies differs between adults and children. In general, studies in
      children will not be performed until efficacy and safety has been demonstrated in
      adults. Exceptions include development of AEDs for seizure types seen only in
      children. Formulation preparation and dosing selection are often more challenging
      in children. Clinical trials including pharmacokinetic studies will be conducted
      in patients. A relatively small number of children, given subdivision into age
      groups and seizure types, are available for study. Clinical trials must be
      designed with children in mind, adjusting the length of the trials and the choice
      of controls. Efficacy extrapolation from adults may be considered for partial
      seizures in children, but not in infants. Seizure counts remain an appropriate
      efficacy endpoint; however, ascertainment in infants and younger children may
      require EEG monitoring. Safety specific to growing and developing children must
      be evaluated and long-term effects monitored.

PMID- 17199019
TI  - Brivaracetam (UCB 34714).
AB  - Brivaracetam (UCB 34714) is chemically related to levetiracetam (LEV, Keppra). It
      possesses a binding affinity for the synaptic vesicle protein 2A (SV2A) ten-fold
      above that of LEV and also shows an ability to inhibit Na+ channels. This
      correlates with a higher potency in suppressing epileptiform responses in vitro
      and a more potent and complete suppression of different seizure types in animals
      with an acquired or genetic epilepsy. Brivaracetam has been tested in a
      comprehensive safety pharmacology, toxicology, developmental toxicology, and
      genotoxicity program. It is of low acute toxicity, target organ for toxic effects
      is the hepatobiliary tract. Carcinogenicity studies are ongoing. Human
      pharmacology studies have shown that brivaracetam has a half-life of 8 h and
      nearly complete bioavailability. Brivaracetam is primarily metabolized via
      hydrolysis of the acetamide group and CYP2C8-mediated hydroxylation. Its
      metabolites are not pharmacologically active. Excretion of over 95% of the dose,
      including metabolites, occurs renally within 72 h. Healthy volunteer studies
      demonstrated a favorable tolerability profile. Treatment emergent adverse events
      were mild to moderate, mostly of CNS origin, and resolved within 24 hrs, with
      decreasing incidence after repeated intake. Drug-drug interaction studies with
      high dose of brivaracetam (400 mg/d) showed a dose-dependent increase of
      carbamazepine-epoxide levels. No significant interaction with low doses of
      phenytoin was observed at the same high dose levels of brivaracetam, and only a
      moderate pharmacokinetic interaction with an oral contraceptive, without impact
      on hormonal levels or ovulation, was observed. The pharmacokinetic profile of
      brivaracetam is unaltered in elderly subjects or those with impaired renal
      function. Clearance of brivaracetam is reduced in patients with hepatic
      insufficiency. In the photoparoxysmal response model in patients with
      photosensitive epilepsy brivaracetam was effective at all tested doses (10 - 80
      mg) in reducing or abolishing EEG discharges evoked by a photic stimulus. Phase 2
      studies in patients with refractory partial onset seizures have recently been
      completed.

PMID- 17199020
TI  - Eslicarbazepine acetate (BIA 2-093).
AB  - Eslicarbazepine acetate (ESL) [(S)-(--)-10-acetoxy-10,11-dihydro-5H
      dibenz[b,f]azepine-5-carboxamide], formerly known as BIA 2-093, is a novel
      central nervous system (CNS)-active compound with anticonvulsant activity. It
      behaves as a voltage-gated sodium channel (VGSC) blocker and is currently under
      clinical development for the treatment of epilepsy and bipolar disorder. ESL
      shares with carbamazepine and oxcarbazepine the dibenzazepine nucleus bearing the
      5-carboxamide substitute, but is structurally different at the 10,11-position.
      This molecular variation results in differences in metabolism, preventing the
      formation of toxic epoxide metabolites such as carbamazepine-10,11 epoxide. In
      pharmacokinetic studies in humans, ESL was rapidly and extensively metabolized to
      eslicarbazepine (S-licarbazepine), which is responsible for pharmacological
      activity. ESL has been tested in patients with refractory partial-onset seizures
      and was found to be efficacious and well tolerated. Monotherapy studies in adult
      epileptic patients and add-on studies in epileptic children are in the planning
      process. The efficacy and safety data appear to be very promising considering the
      refractory nature of the epileptic population enrolled in studies to date.
      Results of ongoing phase III studies in adult epileptic patients are expected to
      be available in 2007 and are required to define the position of ESL in the
      therapy of patients with epilepsy.

PMID- 17199018
TI  - Use of antiepileptic drugs for nonepileptic conditions: psychiatric disorders and
      chronic pain.
AB  - Antiepileptic drugs (AEDs) are commonly utilized for nonepileptic conditions,
      including various psychiatric disorders and pain syndromes. Evidence for their
      benefit in these nonepileptic conditions varies widely among different drugs, but
      there is, in general, a paucity of published multicenter randomized double-blind
      trials. Variable levels of evidence suggest that lamotrigine and the vagal nerve
      stimulator have antidepressant properties. Carbamazepine, valproate, lamotrigine,
      and oxcarbazepine appear to have mood stabilizing properties while gabapentin,
      pregabalin, and tiagabine have anxiolytic benefits. Barbiturates, topiramate, and
      possibly phenytoin may precipitate or exacerbate depression. Underlying
      depression and anxiety symptoms may be exacerbated by levetiracetam, while
      psychotic symptoms have rarely been reported with topiramate, levetiracetam, and
      zonisamide. Pregabalin, gabapentin, carbamazepine, and oxcarbazepine have been
      used to treat neuropathic pain such as postherpetic neuralgia, and diabetic
      polyneuropathy. Topiramate and divalproex sodium have utility in the prophylaxis
      or acute treatment of migraine. Further rigorous studies are needed to clarify
      the utility of AEDs in nonepileptic conditions.

PMID- 17199021
TI  - Fluorofelbamate.
AB  - The incidence of refractory seizures has remained at 30-40%, even with the
      approval of nine new anticonvulsants over the past 12 years. In attempts to
      reduce seizure frequency and severity, physicians routinely resort to combining
      two or more anticonvulsants, ideally with different mechanisms of action. These
      combinatorial therapies are difficult to administer for both patient and
      caregiver and often result in tolerability issues. Hence, a broad spectrum
      anticonvulsant, with multiple mechanisms of action, that is well tolerated, would
      provide physicians with an important option in their armamentarium to control
      seizures. Felbamate initially fit this profile and was demonstrated to
      effectively control both partial and generalized seizures in clinical studies
      supporting registration. Unfortunately, unanticipated idiosyncratic toxicity was
      observed after approval and the drug is now relegated to second or third line
      therapy, depending on patient history and seizure type. Epileptologists still
      prescribe this drug for refractory seizures, and a recent communication indicates
      that 35,000 to 46,000 new patients have tried Felbatol (MedPointe
      Pharmaceuticals, Somerset, NJ) since 1995. The continued utilization of Felbatol,
      in light of its risk:benefit issues, highlights the need for new efficacious
      therapeutic options. Fluorofelbamate (MedPointe Pharmaceuticals), a phase I drug
      candidate, was designed to retain the broad spectrum multimechanistic activity of
      felbamate, with a modified metabolism that has demonstrated, in vitro, to avoid
      the production of the reactive metabolite believed to cause the idiosyncratic
      toxicity. This drug candidate is one of several carbamates either in development
      or currently on the market for treatment of seizures and other CNS disorders.

PMID- 17199022
TI  - Ganaxolone.
AB  - Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) (GNX) is the 3beta
      methylated synthetic analog of allopregnanolone; it belongs to a class of
      compounds referred to as neurosteroids. GNX is an allosteric modulator of GABA(A)
      receptors acting through binding sites which are distinct from the benzodiazepine
      binding site. It has activity in a broad range of animal models of epilepsy. GNX
      has been shown to be well tolerated in adults and children. In early phase II
      studies, GNX has been shown to have activity in adult patients with partial-onset
      seizures and epileptic children with history of infantile spasms. It is currently
      undergoing further development in infants with newly diagnosed infantile spasms,
      in women with catamenial epilepsy, and in adults with refractory partial-onset
      seizures.

PMID- 17199023
TI  - Carisbamate (RWJ-333369).
AB  - Carisbamate (RWJ-333369) is a novel neuromodulator, initially developed by SK
      Biopharmaceuticals (Fairlawn, NJ), under development by Johnson & Johnson
      Pharmaceutical Research and Development (La Jolla, CA). Carisbamate displays high
      potency in a broad range of rodent seizure models at doses well below those that
      produce CNS toxicity. Its mechanism of action has not been elucidated. Acute and
      chronic nonclinical toxicological studies have not revealed any significant
      abnormalities other than dose-related CNS toxicity. It is extensively
      metabolized, chiefly through glucuronidation and oxidation of the aliphatic side
      chain. There is little evidence of CYP metabolism. It has linear
      pharmacokinetics. Its clearance is increased by carbamazepine and to a lesser
      degree by oral contraceptives. Carisbamate slightly increases the clearance of
      valproic acid and lamotrigine. The most common adverse events in humans are
      headaches, dizziness, and somnolence, generally mild to moderate, occurring at
      doses of 1000 mg/day or more. A recently completed phase 2 study for adjunctive
      use in partial onset seizures showed efficacy at a dose that was well tolerated.

PMID- 17199024
TI  - Safinamide.
AB  - Safinamide (SAF) ((S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino)propanamide) was
      initially synthetized by Farmitalia Carlo Erba (Italy). Following initial
      anticonvulsant screening, safinamide was selected for its potency, broad spectrum
      of action, and good safety margin. Pharmacodynamic properties probably relevant
      to its antiepileptic activity are use- and frequency-dependent block of voltage
      sensitive Na+ channels, block of Ca++ channels, and glutamate release inhibition.
      Possibly contributing mechanism are also selective and reversible monoamide
      oxidase B inhibition and dopamine and noradrenaline uptake inhibition. The high
      selectivity for the sigma-1 receptor site does not entail psychotomimetic or
      behavioral changes. In several experimental in vitro and in vivo conditions, SAF
      exerts neurorescuing and neuroprotectant effects. Safinamide is water soluble and
      suitable for 1 times a day oral administration in humans. In a pilot phase II
      study in 38 refractory epilepsy patients affected by multiple types of seizures,
      41% of subjects obtained > or =50% seizure reduction during a 12-week escalating
      dose up to 300 mg 1 times day compared with perspective baseline. Safinamide is
      being developed in phase III for treatment of Parkinson's disease, whereas the
      development in epilepsy relates to the industrial strategy of the company.

PMID- 17199025
TI  - Seletracetam (UCB 44212).
AB  - Better pharmacotherapies for epilepsy are needed for patients who are refractory
      to or have tolerability difficulties with current treatments. Seletracetam, a new
      drug in epilepsy development, is a pyrrolidone derivative structurally related to
      levetiracetam (trade name Keppra). It was discovered because of its high binding
      affinity to the synaptic vesicle 2A (SV2A) protein, which is now known to be the
      binding site for this family of compounds. Seletracetam shows very potent seizure
      suppression in models of acquired or genetic epilepsy, as well as high CNS
      tolerability in various animal models. Pharmacokinetic studies in animals suggest
      that seletracetam is rapidly and highly absorbed, with linear and time
      independent pharmacokinetics. Seletracetam appears neither to inhibit nor to
      induce the major human drug metabolizing enzymes, and it demonstrates low plasma
      protein binding (<10%), which suggests a low potential for drug-drug
      interactions. Initial studies in humans demonstrated first-order
      monocompartmental kinetics with a half-life of 8 h and an oral bioavailability of
      >90%. Studies in healthy volunteers showed that the treatment emergent adverse
      events were of mild to moderate severity, were mostly of CNS origin and were
      resolved within 24 h. Altogether, these results suggest that seletracetam
      represents a promising new antiepileptic drug candidate, one that demonstrates a
      potent, broad spectrum of seizure protection and a high CNS tolerability in
      animal models, with initial clinical findings suggestive of straightforward
      pharmacokinetics and good tolerability.

PMID- 17199026
TI  - Stiripentol.
AB  - Stiripentol (STP) is a new antiepileptic compound made by Biocodex. It recently
      proved to increase the GABAergic transmission in vitro in an experimental model
      of immature rat. Clinical studies were based on the fact that STP also acts as an
      inhibitor of CYP3A4, CYP1A2, and CYP2C19 in vivo in epileptic patients. Whereas
      the studies in adult patients were disappointing, the trials conducted in
      pediatric populations demonstrated a specific efficacy of STP in severe myoclonic
      epilepsy in infancy, Dravet syndrome, when combined with valproate and clobazam.
      Based on these results, STP was granted orphan drug status in the European Union
      for the treatment of Dravet syndrome. The French experience in compassionate use
      suggests that STP might also be of benefit when combined with carbamazepine in
      pediatric patients with pharmacoresistant partial epilepsy. The interactions of
      STP with a large number of drugs need to be carefully taken into account, with
      doses of the combined antiepileptic drugs adjusted to improve the tolerability of
      the therapeutic association.

PMID- 17199015
TI  - Molecular targets for antiepileptic drug development.
AB  - This review considers how recent advances in the physiology of ion channels and
      other potential molecular targets, in conjunction with new information on the
      genetics of idiopathic epilepsies, can be applied to the search for improved
      antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated
      cation channels (the alpha subunits of voltage-gated Na+ channels and also T-type
      voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently,
      alpha2-delta voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle
      protein have been recognized as likely targets. Genetic studies of familial
      idiopathic epilepsies have identified numerous genes associated with diverse
      epilepsy syndromes, including genes encoding Na+ channels and GABA(A) receptors,
      which are known AED targets. A strategy based on genes associated with epilepsy
      in animal models and humans suggests other potential AED targets, including
      various voltage-gated Ca2+ channel subunits and auxiliary proteins, A- or M-type
      voltage-gated K+ channels, and ionotropic glutamate receptors. Recent progress in
      ion channel research brought about by molecular cloning of the channel subunit
      proteins and studies in epilepsy models suggest additional targets, including G
      protein-coupled receptors, such as GABA(B) and metabotropic glutamate receptors;
      hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel
      subunits, responsible for hyperpolarization-activated current Ih; connexins,
      which make up gap junctions; and neurotransmitter transporters, particularly
      plasma membrane and vesicular transporters for GABA and glutamate. New
      information from the structural characterization of ion channels, along with
      better understanding of ion channel function, may allow for more selective
      targeting. For example, Na+ channels underlying persistent Na+ currents or
      GABA(A) receptor isoforms responsible for tonic (extrasynaptic) currents
      represent attractive targets. The growing understanding of the pathophysiology of
      epilepsy and the structural and functional characterization of the molecular
      targets provide many opportunities to create improved epilepsy therapies.

PMID- 17199027
TI  - Talampanel.
AB  - Talampanel is a novel anticonvulsant that acts as an allosteric inhibitor of the
      AMPA receptor. Talampanel has a broad spectrum of action in animal models of
      epilepsy and neuroprotection. Clinical experience to date has been able to show
      effectiveness in reduction of seizures in patients with refractory partial
      seizures.

PMID- 17199028
TI  - Valproic Acid: second generation.
AB  - The manuscript focuses on structure-activity relationship studies of CNS-active
      compounds derived from valproic acid (VPA) that have the potential to become
      second-generation VPA drugs. Valproic acid is one of the four most widely
      prescribed antiepileptic drugs (AEDs) and is effective (and regularly approved)
      in migraine prophylaxis and in the treatment of bipolar disorders. Valproic acid
      is also currently undergoing clinical trials in cancer patients. Valproic acid is
      the least potent of the established AEDs and its use is limited by two rare but
      potentially life-threatening side effects, teratogenicity and hepatotoxicity.
      Because AEDs treat the symptoms (seizure) and not the cause of epilepsy,
      epileptic patients need to take AEDs for a long period of time. Consequently,
      there is a substantial need to develop better and safer AEDs. To become a
      successful second-generation VPA, the new drug should possess the following
      characteristics: broad-spectrum antiepileptic activity, better potency than VPA,
      lack of teratogenicity and hepatotoxicity, and a favorable pharmacokinetic
      profile compared with VPA including a low potential for drug interactions.

PMID- 17199029
TI  - Clobazam.
AB  - Catastrophic childhood epilepsies such as infantile spasms (IS), progressive
      myoclonic epilepsy, and Lennox-Gastaut syndrome (LGS) are rare but debilitating
      and frequently persist into adulthood. Early, targeted use of medications that
      have demonstrated efficacy in the management of LGS or its associated epilepsies
      may simplify the patient's treatment regimen and reduce the incidence of adverse
      events. Key to the overall benefit to the patient is to maximize seizure control
      while minimizing adverse effects, especially behavioral and cognitive problems.
      Clobazam has demonstrated clinical benefit and has been administered safely in
      more than 50 European studies in which data were reported on greater than 3000
      pediatric and adult patients with epilepsy, 300 of whom were diagnosed with LGS;
      therefore, its use is now being investigated in the U.S. This review will explore
      the use of clobazam in the treatment of epilepsy, particularly with regard to its
      potential benefit in LGS. Though not currently approved for use in the U.S., a
      program is underway to gain Food and Drug Administration approval for the
      treatment of pediatric and adult patients with refractory epilepsy, specifically
      in LGS. A phase 2 study will be completed in late 2006 to investigate the safety
      and efficacy of clobazam as adjunctive therapy in 68 pediatric and adult patients
      with LGS.

PMID- 17199030
TI  - Lacosamide.
AB  - Lacosamide is a new chemical entity being investigated as an adjunctive treatment
      for epilepsy, as well as monotherapy for diabetic neuropathic pain. Lacosamide
      appears to have a dual mode of action: selective enhancement of sodium channel
      inactivation and modulation of collapsin response mediator protein-2. Rapidly and
      completely absorbed after oral administration, lacosamide has an elimination half
      life of approximately 13 hours and a low potential for drug interactions.
      Additionally, lacosamide exhibits linear, dose-proportional pharmacokinetics with
      low intra- and interpatient variability. Randomized controlled trials of
      adjunctive lacosamide (200, 400, and 600 mg/day) have demonstrated statistically
      significant reduction in median seizure frequency compared with placebo. In
      addition, 50% responder rates for lacosamide (400 and 600 mg/day) were
      statistically superior to placebo. The most frequently reported adverse events (>
      or =10% of lacosamide-treated patients) included dizziness, headache, and nausea.
      A double-blind, double-dummy randomized trial of intravenous lacosamide (30- and
      60-minute infusion) as replacement for oral lacosamide showed that the safety and
      tolerability profiles were comparable for intravenous and oral lacosamide. The
      efficacy and safety results from completed clinical trials, as well as the
      favorable pharmacokinetic profile, suggest that lacosamide may represent a
      significant advance in antiepileptic drug therapy.

PMID- 17199031
TI  - Retigabine.
AB  - Retigabine is a novel antiseizure drug that acts through potassium channels and
      has activity in a broad range of animal models of epilepsy. It is also effective
      in several preclinical pain models. The drug has been extensively studied in
      phase I and II studies, with very promising results. The maximal tolerated dose
      for most patients is 1,200 mg/day. Adverse effects have been largely CNS-related
      and mild; most have occurred during the titration periods in the various studies.
      At present, retigabine is in two pivotal phase III studies.

PMID- 17199032
TI  - Rufinamide.
AB  - Rufinamide is a triazole derivative structurally unrelated to currently marketed
      antiepileptic drugs. Rufinamide was profiled for anticonvulsant activity at the
      National Institutes of Health and showed broad-spectrum anticonvulsant properties
      at nontoxic doses in animal models. The principal mechanism of action of
      rufinamide is considered to be the modulation of the activity of sodium channels
      and, in particular, prolongation of the inactive state of the channel. Rufinamide
      provides an efficacious and well-tolerated treatment option for use as adjunctive
      therapy in patients with partial seizures and with Lennox-Gastaut syndrome (LGS).
      In LGS, rufinamide is effective in controlling multiple seizure types and in
      reducing the severity of the seizures. The most commonly observed (> or =10%)
      adverse experiences seen in association with rufinamide are headache, dizziness,
      fatigue, somnolence and nausea. Rufinamide is generally well tolerated, and its
      safety profile is well-established.

PMID- 17199034
TI  - Breaking symmetry on time.

PMID- 17199035
TI  - Stress-associated MAP kinase fills in the map of filamin-mediated neuronal
      migration.

PMID- 17199033
TI  - Vigabatrin.
AB  - Refractory epilepsies such as infantile spasms (IS) and complex partial seizures
      (CPS) can have a severe negative impact on the neurological integrity and quality
      of life of affected patients, in addition to drastically increasing their risk of
      premature mortality. Early identification of potentially effective
      pharmacotherapy agents is important. Vigabatrin has been shown to be a generally
      well tolerated and effective antiepileptic drug (AED) in a wide variety of
      seizure types affecting both children and adults, particularly those with IS and
      CPS. A bilateral, concentric constriction of the peripheral visual field
      characterizes the visual field defect (VFD) associated with vigabatrin, well
      characterized by numerous studies. This peripheral VFD presents in 30-50% of
      patients with exposure of several years; however, most of these patients are
      asymptomatic. In well-controlled studies, the earliest onset in patients with CPS
      is 11 months and at 5 months in infants, with average onsets being more than 5
      years and 1 year, respectively. Patients with a peripheral VFD retain an average
      65 degrees of lateral vision (normal, 90 degrees). The fact that many patients
      never develop the vigabatrin-related peripheral VFD, despite long-term exposure
      at high doses, may support the hypothesis that the injury is an idiosyncratic
      adverse drug reaction (as opposed to a strict dose- or duration-dependent
      toxicity). Effective testing methods are available to aid in the early detection
      and management of the peripheral VFD. This article discusses issues of importance
      to clinical decision-making in the use of vigabatrin to assist the physician and
      patient in assessing the benefits of vigabatrin therapy and understanding the
      potential risks of the VFD and uncontrolled seizures.

PMID- 17199036
TI  - TIRFing out studies on Glut4 trafficking.

PMID- 17199037
TI  - Automated subcellular location determination and high-throughput microscopy.

PMID- 17199038
TI  - Priming of centromere for CENP-A recruitment by human hMis18alpha, hMis18beta,
      and M18BP1.
AB  - The centromere is the chromosomal site that joins to microtubules during mitosis
      for proper segregation. Determining the location of a centromere-specific histone
      H3 called CENP-A at the centromere is vital for understanding centromere
      structure and function. Here, we report the identification of three human
      proteins essential for centromere/kinetochore structure and function,
      hMis18alpha, hMis18beta, and M18BP1, the complex of which is accumulated
      specifically at the telophase-G1 centromere. We provide evidence that such
      centromeric localization of hMis18 is essential for the subsequent recruitment of
      de novo-synthesized CENP-A. If any of the three is knocked down by RNAi,
      centromere recruitment of newly synthesized CENP-A is rapidly abolished, followed
      by defects such as misaligned chromosomes, anaphase missegregation, and
      interphase micronuclei. Tricostatin A, an inhibitor to histone deacetylase,
      suppresses the loss of CENP-A recruitment to centromeres in hMis18alpha RNAi
      cells. Telophase centromere chromatin may be primed or licensed by the hMis18
      complex and RbAp46/48 to recruit CENP-A through regulating the acetylation status
      in the centromere.

PMID- 17199039
TI  - Chromosomal enrichment and activation of the aurora B pathway are coupled to
      spatially regulate spindle assembly.
AB  - Chromatin-induced spindle assembly depends on regulation of microtubule
      depolymerizing proteins by the chromosomal passenger complex (CPC), consisting of
      Incenp, Survivin, Dasra (Borealin), and the kinase Aurora B, but the mechanism
      and significance of the spatial regulation of Aurora B activity remain unclear.
      Here, we show that the Aurora B pathway is suppressed in the cytoplasm of Xenopus
      egg extract by phosphatases, but that it becomes activated by chromatin via a Ran
      independent mechanism. While spindle microtubule assembly normally requires Dasra
      dependent chromatin binding of the CPC, this function of Dasra can be bypassed by
      clustering Aurora B-Incenp by using anti-Incenp antibodies, which stimulate
      autoactivation among bound complexes. However, such chromatin-independent Aurora
      B pathway activation promotes centrosomal microtubule assembly and produces
      aberrant achromosomal spindle-like structures. We propose that chromosomal
      enrichment of the CPC results in local kinase autoactivation, a mechanism that
      contributes to the spatial regulation of spindle assembly and possibly to other
      mitotic processes.

PMID- 17199040
TI  - Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through
      activation of an ATR/Chk2 DNA damage response.
AB  - Small repeat-associated siRNAs (rasiRNAs) mediate silencing of retrotransposons
      and the Stellate locus. Mutations in the Drosophila rasiRNA pathway genes
      armitage and aubergine disrupt embryonic axis specification, triggering defects
      in microtubule polarization as well as asymmetric localization of mRNA and
      protein determinants in the developing oocyte. Mutations in the ATR/Chk2 DNA
      damage signal transduction pathway dramatically suppress these axis specification
      defects, but do not restore retrotransposon or Stellate silencing. Furthermore,
      rasiRNA pathway mutations lead to germline-specific accumulation of gamma-H2Av
      foci characteristic of DNA damage. We conclude that rasiRNA-based gene silencing
      is not required for axis specification, and that the critical developmental
      function for this pathway is to suppress DNA damage signaling in the germline.

PMID- 17199041
TI  - The DXPas34 repeat regulates random and imprinted X inactivation.
AB  - X chromosome inactivation (XCI) is initiated by expression of the noncoding Xist
      RNA in the female embryo. Tsix, the antisense noncoding partner of Xist, serves
      as its regulator during both imprinted and random XCI. Here, we show that Tsix in
      part acts through a 34mer repeat, DXPas34. DXPas34 contains bidirectional
      promoter activity, producing overlapping forward and reverse transcripts. We
      generate three new Tsix alleles in mouse embryonic stem cells and show that,
      while the Tsix promoter is unexpectedly dispensable, DXPas34 plays dual positive
      negative functions. At the onset of XCI, DXPas34 stimulates Tsix expression
      through its enhancer activity. Once XCI is established, DXPas34 becomes
      repressive and stably silences Tsix. Germline transmission of the DXPas34
      mutation demonstrates its necessity for both random and imprinted XCI in mice.
      Intriguingly, sequence analysis suggests that DXPas34 could potentially have
      descended from an ancient retrotransposon. We hypothesize that DXPas34 was
      acquired by Tsix to regulate antisense function.

PMID- 17199042
TI  - A morphologically conserved nonapoptotic program promotes linker cell death in
      Caenorhabditis elegans.
AB  - Apoptosis, cell death characterized by stereotypical morphological features,
      requires caspase proteases. Nonapoptotic, caspase-independent cell death pathways
      have been postulated; however, little is known about their molecular constituents
      or in vivo functions. Here, we show that death of the Caenorhabditis elegans
      linker cell during development is independent of the ced-3 caspase and all known
      cell death genes. The linker cell employs a cell-autonomous death program, and a
      previously undescribed engulfment program is required for its clearance. Dying
      linker cells display nonapoptotic features, including nuclear crenellation,
      absence of chromatin condensation, organelle swelling, and accumulation of
      cytoplasmic membrane-bound structures. Similar features are seen during
      developmental death of neurons in the vertebrate spinal cord and ciliary ganglia.
      Linker cell death is controlled by the microRNA let-7 and Zn-finger protein LIN
      29, components of the C. elegans developmental timing pathway. We propose that
      the program executing linker cell death is conserved and used during vertebrate
      development.

PMID- 17199043
TI  - Temporally regulated asymmetric neurogenesis causes left-right difference in the
      zebrafish habenular structures.
AB  - The habenular neurons on both sides of the zebrafish diencephalon show an
      asymmetric (laterotopic) axonal projection pattern into the interpeduncular
      nucleus. We previously revealed that the habenula could be subdivided into medial
      and lateral subnuclei, and a prominent left-right difference in the size ratio of
      these subnuclei accounts for the asymmetry in its neural connectivity. In the
      present study, birth date analysis showed that neural precursors for the lateral
      subnuclei were born at earlier stages than those for the medial subnuclei. More
      neurons for the early-born lateral subnuclei were generated on the left side,
      while more neurons for the late-born medial subnuclei were generated on the right
      side. Genetic hyperactivation and repression of Notch signaling revealed that
      differential timing determines both specificity and asymmetry in the neurogenesis
      of neural precursors for the habenular subnuclei.

PMID- 17199044
TI  - Abnormal hair development and apparent follicular transformation to mammary gland
      in the absence of hedgehog signaling.
AB  - We show that removing the Shh signal tranducer Smoothened from skin epithelium
      secondarily results in excess Shh levels in the mesenchyme. Moreover, the
      phenotypes we observe reflect decreased epithelial Shh signaling, yet increased
      mesenchymal Shh signaling. For example, the latter contributes to exuberant hair
      follicle (HF) induction, while the former depletes the resulting follicular stem
      cell niches. This disruption of the niche apparently also allows the remaining
      stem cells to initiate hair formation at inappropriate times. Thus, the temporal
      structure of the hair cycle may depend on the physical structure of the niche.
      Finally, we find that the ablation of epithelial Shh signaling results in
      unexpected transformations: the follicular outer root sheath takes on an
      epidermal character, and certain HFs disappear altogether, having adopted a
      strikingly mammary gland-like fate. Overall, our study uncovers a multifaceted
      function for Shh in sculpting and maintaining the integrity and identity of the
      developing HF.

PMID- 17199045
TI  - Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes
      bone formation.
AB  - Wnt signaling regulates a variety of developmental processes in animals. Although
      the beta-catenin-dependent (canonical) pathway is known to control cell fate, a
      similar role for noncanonical Wnt signaling has not been established in mammals.
      Moreover, the intracellular cascades for noncanonical Wnt signaling remain to be
      elucidated. Here, we delineate a pathway in which Wnt3a signals through the
      Galpha(q/11) subunits of G proteins to activate phosphatidylinositol signaling
      and PKCdelta in the murine ST2 cells. Galpha(q/11)-PKCdelta signaling is required
      for Wnt3a-induced osteoblastogenesis in these cells, and PKCdelta homozygous
      mutant mice exhibit a deficit in embryonic bone formation. Furthermore, Wnt7b,
      expressed by osteogenic cells in vivo, induces osteoblast differentiation in
      vitro via the PKCdelta-mediated pathway; ablation of Wnt7b in skeletal
      progenitors results in less bone in the mouse embryo. Together, these results
      reveal a Wnt-dependent osteogenic mechanism, and they provide a potential target
      pathway for designing therapeutics to promote bone formation.

PMID- 17199047
TI  - SMAUG is a major regulator of maternal mRNA destabilization in Drosophila and its
      translation is activated by the PAN GU kinase.
AB  - In animals, egg activation triggers a cascade of posttranscriptional events that
      act on maternally synthesized RNAs. We show that, in Drosophila, the PAN GU (PNG)
      kinase sits near the top of this cascade, triggering translation of SMAUG (SMG),
      a multifunctional posttranscriptional regulator conserved from yeast to humans.
      Although PNG is required for cytoplasmic polyadenylation of smg mRNA, it
      regulates translation via mechanisms that are independent of its effects on the
      poly(A) tail. Analyses of mutants suggest that PNG relieves translational
      repression by PUMILIO (PUM) and one or more additional factors, which act in
      parallel through the smg mRNA's 3' untranslated region (UTR). Microarray-based
      gene expression profiling shows that SMG is a major regulator of maternal
      transcript destabilization. SMG-dependent mRNAs are enriched for gene ontology
      annotations for function in the cell cycle, suggesting a possible causal
      relationship between failure to eliminate these transcripts and the cell cycle
      defects in smg mutants.

PMID- 17199048
TI  - The Drosophila PNG kinase complex regulates the translation of cyclin B.
AB  - The Drosophila PAN GU (PNG) kinase complex regulates the developmental
      translation of cyclin B. cyclin B mRNA becomes unmasked during oogenesis
      independent of PNG activity, but PNG is required for translation from egg
      activation. We find that although polyadenylation of cyclin B augments
      translation, it is not essential, and a fully elongated poly(A) is not required
      for translation to proceed. In fact, changes in poly(A) tail length are not
      sufficient to account for PNG-mediated control of cyclin B translation and of the
      early embryonic cell cycles. We present evidence that PNG functions instead as an
      antagonist of PUMILIO-dependent translational repression. Our data argue that
      changes in poly(A) tail length are not a universal mechanism governing embryonic
      cell cycles, and that PNG-mediated derepression of translation is an important
      alternative mechanism in Drosophila.

PMID- 17199049
TI  - The Tempest.

PMID- 17199046
TI  - Association of Dishevelled with the clathrin AP-2 adaptor is required for
      Frizzled endocytosis and planar cell polarity signaling.
AB  - Upon activation by Wnt, the Frizzled receptor is internalized in a process that
      requires the recruitment of Dishevelled. We describe a novel interaction between
      Dishevelled2 (Dvl2) and micro2-adaptin, a subunit of the clathrin adaptor AP-2;
      this interaction is required to engage activated Frizzled4 with the endocytic
      machinery and for its internalization. The interaction of Dvl2 with AP-2 requires
      simultaneous association of the DEP domain and a peptide YHEL motif within Dvl2
      with the C terminus of micro2. Dvl2 mutants in the YHEL motif fail to associate
      with micro2 and AP-2, and prevent Frizzled4 internalization. Corresponding
      Xenopus Dishevelled mutants show compromised ability to interfere with
      gastrulation mediated by the planar cell polarity (PCP) pathway. Conversely, a
      Dvl2 mutant in its DEP domain impaired in PCP signaling exhibits defective AP-2
      interaction and prevents the internalization of Frizzled4. We suggest that the
      direct interaction of Dvl2 with AP-2 is important for Frizzled internalization
      and Frizzled/PCP signaling.

PMID- 17199050
TI  - The surprisingly rich contours of schizophrenia epidemiology.

PMID- 17199051
TI  - Lifetime prevalence of psychotic and bipolar I disorders in a general population.
AB  - CONTEXT: Recent general population surveys of psychotic disorders have found low
      lifetime prevalences. However, this may be owing to methodological problems. Few
      studies have reported the prevalences of all specific psychotic disorders.
      OBJECTIVE: To provide reliable estimates of the lifetime prevalences of specific
      psychotic disorders. DESIGN: General population survey. SETTING AND PARTICIPANTS:
      A nationally representative sample of 8028 persons 30 years or older was screened
      for psychotic and bipolar I disorders using the Composite International
      Diagnostic Interview, self-reported diagnoses, medical examination, and national
      registers. Those selected by the screens were then re-interviewed with the
      Structured Clinical Interview for DSM-IV. Best-estimate DSM-IV diagnoses were
      formed by combining the interview and case note data. Register diagnoses were
      used to estimate the effect of the nonresponders. MAIN OUTCOME MEASURES:
      Diagnosis of any psychotic or bipolar I disorder according to the DSM-IV
      criteria. RESULTS: The lifetime prevalence of all psychotic disorders was 3.06%
      and rose to 3.48% when register diagnoses of the nonresponder group were
      included. Lifetime prevalences were as follows: 0.87% for schizophrenia, 0.32%
      for schizoaffective disorder, 0.07% for schizophreniform disorder, 0.18% for
      delusional disorder, 0.24% for bipolar I disorder, 0.35% for major depressive
      disorder with psychotic features, 0.42% for substance-induced psychotic
      disorders, and 0.21% for psychotic disorders due to a general medical condition.
      The National Hospital Discharge Register was the most reliable of the screens
      (kappa = 0.80). Case notes supplementing the interviews were essential for
      specific diagnoses of psychotic disorders. CONCLUSIONS: Multiple sources of
      information are essential for accurate estimation of lifetime prevalences of
      psychotic disorders. The use of comprehensive methods reveals that their lifetime
      prevalence exceeds 3%.

PMID- 17199052
TI  - Elevated prenatal homocysteine levels as a risk factor for schizophrenia.
AB  - CONTEXT: Elevated prenatal homocysteine level is a plausible risk factor for
      schizophrenia because of its partial antagonism of N-methyl-D-aspartate receptors
      under physiologic glycine concentrations and its association with abnormal
      placental function and pregnancy complications. OBJECTIVE: We examined whether
      elevated maternal levels of homocysteine during the third trimester were
      associated with adult schizophrenia risk. DESIGN: Nested case-control study of a
      large birth cohort, born from 1959 through 1967 and followed up for schizophrenia
      from 1981 through 1997. SETTING: Population-based birth cohort and health plan.
      PARTICIPANTS: Cases (n = 63) were diagnosed with schizophrenia and other spectrum
      disorders (mostly schizophrenia and schizoaffective disorder). Controls (n = 122)
      belonged to the birth cohort; had not been diagnosed with a schizophrenia
      spectrum or major affective disorder; and were matched to cases on date of birth,
      sex, length of time in the cohort, and availability of maternal serum samples.
      MAIN MEASURES: Archived maternal serum samples were assayed for homocysteine
      levels during pregnancies of cases and matched controls. RESULTS: In a model that
      tested for a threshold effect of third-trimester homocysteine levels, an elevated
      homocysteine level was associated with a greater than 2-fold statistically
      significant increase in schizophrenia risk (odds ratio, 2.39; 95% confidence
      interval, 1.18-4.81; P = .02). CONCLUSIONS: These findings indicate that elevated
      third-trimester homocysteine levels may be a risk factor for schizophrenia.
      Elevated third-trimester homocysteine levels may elevate schizophrenia risk
      through developmental effects on brain structure and function and/or through
      subtle damage to the placental vasculature that compromises oxygen delivery to
      the fetus. If future studies both replicate this association and support a causal
      link, then the use of folic acid supplementation would merit evaluation as a
      strategy for prevention of schizophrenia in offspring.

PMID- 17199053
TI  - Incidence of hospitalization for postpartum psychotic and bipolar episodes in
      women with and without prior prepregnancy or prenatal psychiatric
      hospitalizations.
AB  - CONTEXT: Postpartum psychosis occurs in 1 to 2 cases per 1000 live births. Most
      studies have not distinguished postpartum psychosis from bipolar disorder or the
      proportion of the incidence attributable to prepregnancy psychiatric morbidity.
      OBJECTIVE: To determine the incidence of postpartum psychosis and bipolar
      disorder attributable to previous psychiatric hospitalization. DESIGN: Population
      based study using linked registry data to determine postpartum onset of psychotic
      and bipolar episodes within 90 days after the first birth, by women with and
      without prepregnancy or prenatal psychiatric hospitalization. We assessed the
      type, number, and recency of previous hospitalizations on the incidence of
      hospitalization for postpartum psychotic and bipolar episodes. SETTING:
      Nationwide Swedish Hospital Discharge and Medical Birth registers. PATIENTS:
      Swedish women delivering a first live infant between January 1, 1987, and
      December 31, 2001. MAIN OUTCOME MEASURES: Postpartum hospitalization for
      psychosis or bipolar disorder. RESULTS: The cumulative incidences for postpartum
      psychotic and bipolar episodes (adjusted for age at first birth) were 0.07% and
      0.03%, respectively. The incidence of psychiatric hospitalizations for postpartum
      psychotic or bipolar episodes among women without previous psychiatric
      hospitalizations was 0.04% and 0.01% of first births, respectively; for women
      with any psychiatric hospitalization before delivery, the incidence was 9.24% and
      4.48%, respectively. For postpartum psychotic and bipolar episodes, the risk
      increased significantly with the recency of prepregnancy hospitalizations, number
      of previous hospitalizations, and length of most recent hospitalization. More
      than 40% of women hospitalized during the prenatal period for a bipolar or a
      psychotic condition were hospitalized again during the postpartum period.
      Approximately 90% of all postpartum psychotic and bipolar episodes occurred
      within the first 4 weeks after delivery. CONCLUSIONS: Almost 10% of women
      hospitalized for psychiatric morbidity before delivery develop postpartum
      psychosis after their first birth. This underscores the need for obstetricians to
      assess history of psychiatric symptoms and, with pediatric and psychiatric
      colleagues, to optimize the treatment of mothers with psychiatric diagnoses
      through childbirth.

PMID- 17199054
TI  - A prospective investigation of major depressive disorder and comorbidity in
      abused and neglected children grown up.
AB  - CONTEXT: Few prospective longitudinal studies have examined the relationship
      between abuse or neglect in childhood and depression in adulthood. OBJECTIVE: To
      determine whether abused and neglected children were at elevated risk of major
      depressive disorder (MDD) and psychiatric comorbidity, compared with matched
      control subjects, when followed up into young adulthood. DESIGN: Prospective
      cohort design study. SETTING: Midwestern metropolitan county area. PARTICIPANTS:
      Children with substantiated cases of physical and sexual abuse and neglect
      (before the age of 11 years) from January 1, 1967, to December 31, 1971 (n = 676)
      were matched based on age, race, sex, and approximate family social class with a
      group of non-abused and non-neglected children (n = 520) and followed up into
      young adulthood (mean age, 28.7 years). MAIN OUTCOME MEASURES: Between October
      20, 1989, and December 22, 1995, 2-hour in-person interviews were conducted,
      using the National Institute of Mental Health Diagnostic Interview Schedule,
      Version III Revised, to determine DSM-III-R MDD and other psychiatric diagnoses.
      RESULTS: Child abuse and neglect were associated with an increased risk for
      current MDD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.06-2.14; P<
      or=.05) in young adulthood. Children who were physically abused (OR, 1.59; 95%
      CI, 1.00-2.52; P< or =.05) or experienced multiple types of abuse (OR, 1.75; 95%
      CI, 1.01-3.02; P< or =.05) were at increased risk of lifetime MDD, whereas
      neglect increased risk for current MDD (OR, 1.59; 95% CI, 1.10-2.29; P<.01).
      Childhood sexual abuse was not associated with elevated risk of MDD. Kaplan-Meier
      age-of-onset curves (log-rank statistic, 4.03; df = 1; P=.04) showed earlier
      onset of MDD for abused and neglected children compared with controls. Among
      those with MDD, comorbidity was higher for abused and neglected individuals than
      for controls. CONCLUSION: These results support the need for clinicians to
      increase efforts to detect and treat depression in physically abused and
      neglected children.

PMID- 17199055
TI  - Effects of co-occurring cannabis use disorders on the course of bipolar disorder
      after a first hospitalization for mania.
AB  - CONTEXT: Cannabis use disorders commonly co-occur in bipolar disorder; however,
      the effects of cannabis abuse on outcome have been minimally studied. OBJECTIVE:
      To identify how the sequence of the onsets of a cannabis use disorder and bipolar
      disorder is associated with the subsequent course of each condition. DESIGN:
      Inception cohort. SETTING: Academic medical center. PATIENTS: Patients (N = 144)
      were studied who met criteria for bipolar I disorder (manic or mixed), were 12 to
      45 years old, and had no previous hospitalizations and minimal previous
      treatment. Patients were followed up for up to 5 years and included 33 in whom
      the onset of a cannabis use disorder preceded the onset of bipolar disorder
      (cannabis first), 36 in whom bipolar disorder onset preceded the onset of
      cannabis abuse (bipolar first), and 75 with bipolar disorder only. MAIN OUTCOME
      MEASURES: Symptomatic recovery and recurrence of both conditions and percentage
      of follow-up time with affective and cannabis use disorder symptoms. RESULTS: The
      cannabis first group exhibited better recovery than the other groups, although
      when adjusted for potential mediator variables these results did not persist.
      Cannabis use was associated with more time in affective episodes and with rapid
      cycling. Most cannabis use disorders remitted immediately after hospitalization,
      followed by rapid rates of recurrence. CONCLUSIONS: The effects of the sequence
      of onsets of bipolar and cannabis use disorders were less pronounced than
      observed in co-occurring alcohol and bipolar disorders. Aggressive drug abuse
      treatment immediately after a first psychiatric hospitalization might decrease
      rates of recurrence and new cases of cannabis use disorder in the course of
      bipolar disorder.

PMID- 17199056
TI  - Cost-effectiveness of systematic depression treatment among people with diabetes
      mellitus.
AB  - CONTEXT: Depression co-occurring with diabetes mellitus is associated with higher
      health services costs, suggesting that more effective depression treatment might
      reduce use of other medical services. OBJECTIVE: To evaluate the incremental cost
      and cost-effectiveness of a systematic depression treatment program among
      outpatients with diabetes. DESIGN: Randomized controlled trial comparing
      systematic depression treatment program with care as usual. SETTING: Primary care
      clinics of group-model prepaid health plan. PATIENTS: A 2-stage screening process
      identified 329 adults with diabetes and current depressive disorder.
      INTERVENTION: Specialized nurses delivered a 12-month, stepped-care depression
      treatment program beginning with either problem-solving treatment psychotherapy
      or a structured antidepressant pharmacotherapy program. Subsequent treatment
      (combining psychotherapy and medication, adjustments to medication, and specialty
      referral) was adjusted according to clinical response. MAIN OUTCOME MEASURES:
      Depressive symptoms were assessed by blinded telephone assessments at 3, 6, 12,
      and 24 months. Health service costs were assessed using health plan accounting
      records. RESULTS: Over 24 months, patients assigned to the intervention
      accumulated a mean of 61 additional days free of depression (95% confidence
      interval [CI], 11 to 82 days) and had outpatient health services costs that
      averaged $314 less (95% CI, $1007 less to $379 more) compared with patients
      continuing in usual care. When an additional day free of depression is valued at
      $10, the net economic benefit of the intervention is $952 per patient treated
      (95% CI, $244 to $1660). CONCLUSIONS: For adults with diabetes, systematic
      depression treatment significantly increases time free of depression and appears
      to have significant economic benefits from the health plan perspective.
      Depression screening and systematic depression treatment should become routine
      components of diabetes care.

PMID- 17199057
TI  - Altered pain processing in veterans with posttraumatic stress disorder.
AB  - CONTEXT: Posttraumatic stress disorder (PTSD) is a chronic and debilitating
      anxiety disorder. Several brain areas related to pain processing are implicated
      in PTSD. To our knowledge, no functional imaging study has discussed whether
      patients with PTSD experience and process pain in a different way than control
      subjects. OBJECTIVE: To examine neural correlates of pain processing in patients
      with PTSD. DESIGN: The experimental procedure consisted of psychophysical
      assessment and neuroimaging with functional magnetic resonance imaging. Two
      conditions were assessed during functional magnetic resonance imaging in both
      experimental groups, one condition with administration of a fixed temperature of
      43 degrees C (fixed-temperature condition) and the other condition with an
      individual temperature for each subject but with a similar affective label
      equaling 40% of the subjective pain intensity (individual temperature condition).
      SETTING: Academic outpatient unit in a department of military psychiatry in
      collaboration with an imaging center at a psychiatric hospital. PARTICIPANTS:
      Twelve male veterans with PTSD and 12 male veterans without PTSD were recruited
      and matched for age, region of deployment, and year of deployment. MAIN OUTCOME
      MEASURES: Changes in functional magnetic resonance imaging blood oxygenation
      level-dependent response to heat stimuli, reflecting increased and decreased
      activity of brain areas involved in pain processing. RESULTS: Patients with PTSD
      rated temperatures in the fixed-temperature assessment as less painful compared
      with controls. In the fixed-temperature condition, patients with PTSD revealed
      increased activation in the left hippocampus and decreased activation in the
      bilateral ventrolateral prefrontal cortex and the right amygdala. In the
      individual temperature condition, patients with PTSD showed increased activation
      in the right putamen and bilateral insula, as well as decreased activity in the
      right precentral gyrus and the right amygdala. CONCLUSIONS: These data provide
      evidence for reduced pain sensitivity in PTSD. The witnessed neural activation
      pattern is proposed to be related to altered pain processing in patients with
      PTSD.

PMID- 17199058
TI  - Trends in the inpatient mental health treatment of children and adolescents in US
      community hospitals between 1990 and 2000.
AB  - CONTEXT: Previous work has demonstrated marked changes in inpatient mental health
      service use by children and adolescents in the 1980s and early 1990s, but more
      recent, comprehensive, nationally representative data have not been reported.
      OBJECTIVE: To describe trends in inpatient treatment of children and adolescents
      with mental disorders between 1990 and 2000. DESIGN AND SETTING: Analysis of the
      Healthcare Cost and Utilization Project Nationwide Inpatient Sample, a nationally
      representative sample of discharges from US community hospitals sponsored by the
      Agency for Healthcare Research and Quality. PATIENTS: Patients aged 17 years and
      younger discharged from US community hospitals with a principal diagnosis of a
      mental disorder. MAIN OUTCOME MEASURES: Changes in the number and population
      based rate of discharges, total inpatient days and average length of stay,
      charges, diagnoses, dispositions, and patient demographic and hospital
      characteristics. RESULTS: Although the total number of discharges, population
      based discharge rate, and daily charges did not significantly change between 1990
      and 2000, the total number of inpatient days and mean charges per visit each fell
      by approximately one half. Median length of stay declined 63% over the decade
      from 12.2 days to 4.5 days. Declines in median and mean lengths of stay were
      observed for most diagnostic categories and remained significant after
      controlling for changes in background patient and hospital characteristics.
      Discharge rates for psychotic and mood disorders as well as intentional self
      injuries increased while rates for adjustment disorders fell. Discharges to short
      term, nursing, and other inpatient facilities declined. CONCLUSIONS: The period
      between 1990 and 2000 was characterized by a transformation in the length of
      inpatient mental health treatment for young people. Community hospitals
      evaluated, treated, and discharged mentally ill children and adolescents far more
      quickly than 10 years earlier despite higher apparent rates of serious illness
      and self-harm and fewer transfers to intermediate and inpatient care.

PMID- 17199059
TI  - Abnormal attention modulation of fear circuit function in pediatric generalized
      anxiety disorder.
AB  - CONTEXT: Considerable work implicates abnormal neural activation and disrupted
      attention to facial-threat cues in adult anxiety disorders. However, in pediatric
      anxiety, no research has examined attention modulation of neural response to
      threat cues. OBJECTIVE: To determine whether attention modulates amygdala and
      cortical responses to facial-threat cues differentially in adolescents with
      generalized anxiety disorder and in healthy adolescents. DESIGN: Case-control
      study. SETTING: Government clinical research institute. PARTICIPANTS: Fifteen
      adolescents with generalized anxiety disorder and 20 controls. MAIN OUTCOME
      MEASURES: Blood oxygenation level-dependent signal as measured via functional
      magnetic resonance imaging. During imaging, participants completed a face-emotion
      rating task that systematically manipulated attention. RESULTS: While attending
      to their own subjective fear, patients, but not controls, showed greater
      activation to fearful faces than to happy faces in a distributed network
      including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex
      (P<.05, small-volume corrected, for all). Right amygdala findings appeared
      particularly strong. Functional connectivity analyses demonstrated positive
      correlations among the amygdala, ventral prefrontal cortex, and anterior
      cingulate cortex. CONCLUSIONS: This is the first evidence in juveniles that
      generalized anxiety disorder-associated patterns of pathologic fear circuit
      activation are particularly evident during certain attention states.
      Specifically, fear circuit hyperactivation occurred in an attention state
      involving focus on subjectively experienced fear. These findings underscore the
      importance of attention and its interaction with emotion in shaping the function
      of the adolescent human fear circuit.

PMID- 17199060
TI  - Prospective study of posttraumatic stress disorder symptoms and coronary heart
      disease in the Normative Aging Study.
AB  - CONTEXT: Various correlates of posttraumatic stress disorder (PTSD), such as high
      levels of sympathetic activation and hypothalamic-pituitary-adrenal axis
      dysregulation, have been linked to arterial damage and coronary heart disease
      (CHD) risk. While psychological disturbance is frequently found among patients
      with cardiac disease, whether psychological problems precede or occur as a result
      of having a potentially fatal disease is not clear. To our knowledge, no
      prospective studies to date have evaluated whether PTSD is associated with
      increased risk of CHD. OBJECTIVE: To test the hypothesis that high levels of PTSD
      symptoms may increase CHD risk, using 2 different measures of PTSD. DESIGN:
      Prospective cohort study. SETTING: Community-dwelling men from the Greater
      Boston, Mass, area who served in the military. PARTICIPANTS: Data are from the
      Veterans Affairs Normative Aging Study. Men who completed either the Mississippi
      Scale for Combat-Related PTSD in 1990 (n = 1002) or the Keane PTSD scale in 1986
      (n = 944) were included in the study. MAIN OUTCOME MEASURE: Incident CHD
      occurring during follow-up through May 2001. RESULTS: Levels of PTSD symptoms in
      this cohort were low to moderate. Men with preexisting CHD at baseline were
      excluded, and PTSD was measured with the Mississippi Scale for Combat-Related
      PTSD. For each SD increase in symptom level, men had age-adjusted relative risks
      of 1.26 (95% confidence interval, 1.05-1.51) for nonfatal myocardial infarction
      and fatal CHD combined and 1.21 (95% confidence interval, 1.05-1.41) for all of
      the CHD outcomes combined (nonfatal myocardial infarction, fatal CHD, and
      angina). Findings were replicated using the Keane PTSD scale and somewhat
      strengthened after controlling for levels of depressive symptoms. CONCLUSIONS: To
      our knowledge, this is the first study to demonstrate a prospective association
      between PTSD symptoms and CHD even after controlling for depressive symptoms.
      These results suggest that a higher level of PTSD symptoms may increase the risk
      of incident CHD in older men.

PMID- 17199061
TI  - Resource utilization and expenditures for overweight and obese children.
AB  - OBJECTIVES: To compare health care utilization and expenditures for healthy
      weight patients, overweight patients, and patients with diagnosed and undiagnosed
      obesity and to examine factors associated with a diagnosis of obesity. DESIGN:
      Retrospective study using claims data from a large pediatric integrated delivery
      system. SETTING: An urban academic children's hospital. PARTICIPANTS: Children
      aged 5 to 18 years who presented to a primary care clinic for well-child care
      visits during the calendar years 2002 and 2003 and who were followed up for 12
      months. MAIN OUTCOME MEASURES: Diagnosis of obesity, primary care visits,
      emergency department visits, laboratory use, and health care charges. RESULTS: Of
      8404 patients, 57.9% were 10 years or older, 61.2% were African American, and
      72.9% were insured by Medicaid. According to the criteria of body mass index
      (calculated as weight in kilograms divided by the square of height in meters),
      17.8% were overweight and 21.9% were obese. Of the obese children, 42.9% had a
      diagnosis of obesity. Increased laboratory use was found in both children with
      diagnosed obesity (odds ratio [OR], 5.49; 95% confidence interval [CI], 4.65
      6.48) and children with undiagnosed obesity (OR, 2.32; 95% CI, 1.97-2.74),
      relative to the healthy-weight group. Health care expenditures were significantly
      higher for children with diagnosed obesity (adjusted mean difference, $172; 95%
      CI, $138-$206) vs the healthy-weight group. Factors associated with the diagnosis
      of obesity were age 10 years and older (OR, 2.7; 95% CI, 2.0-3.4), female sex
      (OR, 1.5; 95% CI, 1.2-1.8), and having Medicaid (OR, 1.6; 95% CI, 1.1-2.3).
      CONCLUSIONS: Increased health care utilization and charges reported in obese
      adults are also present in obese children. Most children with obesity had not
      been diagnosed as having obesity in this administrative data set.

PMID- 17199062
TI  - Overweight among young children in the Philadelphia health care centers:
      incidence and prevalence.
AB  - OBJECTIVES: To estimate the prevalence and incidence of overweight among low
      income, inner-city children aged 3 to 7 years and to determine predictors of
      changes in body mass index (BMI) (calculated as weight in kilograms divided by
      height in meters squared) percentile. DESIGN: Retrospective cohort study using
      administrative and medical records. SETTING: The Philadelphia Health Care
      Centers, 1996 through 2003. PARTICIPANTS: Three hundred eighty-six patients who
      had at least 2 well-child visits between the ages of 3 and 7 years, had at least
      1 visit between September 2001 and 2003, and were between the ages of 5 and 7
      years at the most recent visit. Mean follow-up time was 2.4 years. MAIN
      EXPOSURES: Age, sex, race/ethnicity, and BMI percentile at baseline. MAIN OUTCOME
      MEASURES: Prevalence and incidence of overweight and at risk of overweight and
      change in BMI percentile. RESULTS: Prevalence of overweight at the initial visit
      was 18%, with 16% at risk of overweight. At the last visit, the prevalence of
      overweight was 19%, with 15% at risk of overweight. Based on maximum BMI
      percentile, 29% were overweight at some point and an additional 19% were at risk
      of overweight at least once. Annualized incidence of overweight among those not
      overweight at baseline was 5% per year: 2% per year for normal-weight children
      and 14% per year for children in the at-risk category. The outcomes were not
      associated with sex, race/ethnicity, or age at first or last visit. Incident
      overweight was positively associated with BMI percentile at baseline. CONCLUSION:
      The early onset and frequent persistence of overweight demonstrated herein
      underline the need to prevent overweight among very young children.

PMID- 17199063
TI  - Externalizing and attentional behaviors in children of depressed mothers treated
      with a selective serotonin reuptake inhibitor antidepressant during pregnancy.
AB  - OBJECTIVE: To evaluate attentional and activity behaviors in 4-year-olds
      following prenatal selective serotonin reuptake inhibitor (SSRI) exposure.
      DESIGN: Prospective cohort design. SETTING: Tertiary care center. PARTICIPANTS:
      Twenty-two 4-year-olds with prolonged prenatal SSRI medication exposure and 14
      children without prenatal exposure. MAIN EXPOSURE: Prenatal SSRI exposure. MAIN
      OUTCOME MEASURES: Group differences in externalizing behaviors (according to the
      Child Behavior Checklist) and direct observations of child attention, activity,
      and impulsiveness in a laboratory setting using the procedure by Crowell and
      colleagues were compared, including measures of the duration of prenatal SSRI
      exposure, umbilical cord drug levels, a history of poor neonatal adaptation, and
      maternal mood. RESULTS: Externalizing behaviors did not differ between groups.
      Maternal depression and anxiety at the 4-year follow-up were associated with
      increased reports of externalizing behaviors. Increased externalizing behaviors
      were associated with increased umbilical cord drug levels (F(1,34) = 6.3; P =
      .02), but when controlling for maternal depressed mood at the 4-year follow-up,
      such levels only accounted for 11.2% of the behavioral outcomes (P>.05). On
      direct observation, the persistence score for child behavior was significantly
      lower in the exposed group. Increased aggressiveness scores were associated with
      a history of poor neonatal adaptation, even when parental report of stress was
      added to the model (F(1,34) = 4.0; P = .03); however, neither parental report of
      stress nor poor neonatal adaptation were significant (both P = .09), suggesting
      that both are important, if not unique, predictors of child behavior.
      CONCLUSIONS: These findings suggest that the best predictors of externalizing
      behaviors at age 4 years are current maternal mood and parental stress,
      regardless of prenatal depressed mood and SSRI treatment during pregnancy. It
      remains uncertain whether poor neonatal adaptation can be excluded as a possible
      predictor of externalizing behaviors.

PMID- 17199064
TI  - Disparities in pediatric preventive care in the United States, 1993-2002.
AB  - OBJECTIVES: To quantify physician-reported preventive counseling and screening
      during well-child visits (WCVs) and to examine racial and ethnic disparities in
      these activities. DESIGN: Cross-sectional study using the National Ambulatory
      Medical Care Survey, January 1993 through December 2002. SETTING: Office-based
      physician practices. PARTICIPANTS: Children from birth to 18 years old who were
      seen by a physician for a WCV. MAIN OUTCOME MEASURE: Preventive counseling and
      screening. RESULTS: Well-child visits were shorter for Latino children than for
      white or black children. At WCVs, white children were more likely to receive
      preventive counseling than were black or Latino children (72% vs 61% vs 61%,
      respectively; P = .01) but not more likely to receive screening for elevated
      blood pressure, anemia, vision and hearing acuity, or lead toxicity. There were
      no differences in secondary diagnoses made at WCVs for white, black, or Latino
      children (15% vs 17% vs 14%, respectively; P = .65). The children who received
      the least counseling were Latino children in the public sector non-health
      maintenance organization setting (counseled at 39% of visits) and Latino children
      who self-paid for the visits (counseled at 26% of visits). After adjusting for
      possible confounders, including medications prescribed at the visit, black and
      Latino children were less likely to receive counseling than were white children
      (odds ratios, 0.68 and 0.63; 95% confidence interval, 0.48-0.97 and 0.44-0.90,
      respectively), and black children were less likely to receive preventive
      screening services (odds ratios, 0.65; 95% confidence interval, 0.45-0.93).
      CONCLUSIONS: By physician report in a nationally representative sample, black and
      Latino children received less counseling at WCVs than did white children. These
      disparities were unexplained by the competing demands of other secondary
      diagnoses or medications prescribed or dispensed.

PMID- 17199065
TI  - Hospital volumes for common pediatric specialty operations.
AB  - OBJECTIVES: To describe hospital volumes for common pediatric specialty
      operations, to evaluate hospital and patient characteristics associated with
      operations performed at a low-volume hospital, and to evaluate outcomes with
      hospital volume. DESIGN: Retrospective cohort using the Kids' Inpatient Database
      2003. SETTING: Discharges from 3438 hospitals in 36 states from 2003.
      PARTICIPANTS: Children aged 0 to 18 years undergoing ventriculoseptal defect
      surgery (n = 2301), tracheotomy (n = 2674), ventriculoperitoneal shunt placement
      (n = 3378), and posterior spinal fusion (n = 4002). MAIN EXPOSURE: Hospital
      volume. MAIN OUTCOME MEASURES: In-hospital mortality and postoperative
      complications. RESULTS: For tracheotomy and posterior spinal fusion, at least one
      fourth of the hospitals performed only 1 operation for children aged 0 to 18
      years in 2003. For these same operations, at least half of hospitals treated 4 or
      fewer cases per year. For all operations, discharges from low-volume hospitals
      were less likely to be from children's or teaching hospitals compared with
      discharges from higher-volume hospitals. For tracheotomy, children were less
      likely to experience postoperative complications in high-volume hospitals
      compared with low-volume hospitals (odds ratio, 0.48; 95% confidence interval,
      0.21-1.09). CONCLUSIONS: Many children undergoing common pediatric specialty
      operations had these procedures performed in low-volume hospitals. Low-volume
      hospitals were less likely to be children's or teaching hospitals. Children
      undergoing tracheotomy experienced higher rates of complications in low-volume
      hospitals. Further research is needed to identify the reasons why so many
      children have these operations performed in low-volume hospitals.

PMID- 17199066
TI  - Effect of multisource feedback on resident communication skills and
      professionalism: a randomized controlled trial.
AB  - OBJECTIVE: To determine whether augmenting standard feedback on resident
      performance with a multisource feedback intervention improved pediatric resident
      communication skills and professionalism. DESIGN: Randomized controlled trial.
      SETTING: Children's Hospital Medical Center, Cincinnati, Ohio, from June 21,
      2004, to July 7, 2005. PARTICIPANTS: Thirty-six first-year pediatric residents.
      INTERVENTIONS: Residents assigned to the multisource feedback group (n = 18)
      completed a self-assessment, received a feedback report about baseline parent and
      nurse evaluations, and participated in a tailored coaching session in addition to
      receiving standard feedback. Residents in the control group (n = 18) received
      standard feedback only. The control group and their residency directors were
      blinded to parent and nurse evaluations until the end of the study. MAIN OUTCOME
      MEASURES: Residents' specific communication skills and professional behaviors
      were rated by parents and nurses of pediatric patients. Both groups were
      evaluated at baseline and after 5 months. Scores were calculated on each item as
      percentage in the highest response category. RESULTS: Both groups had comparable
      baseline characteristics and ratings. Parent ratings increased for both groups.
      While parent ratings increased more for the multisource feedback group,
      differences between groups were not statistically significant. In contrast, nurse
      ratings increased for the multisource feedback group and decreased for the
      control group. The difference in change between groups was statistically
      significant for communicating effectively with the patient and family (35%; 95%
      confidence interval, 11.0%-58.0%), timeliness of completing tasks (30%; 95%
      confidence interval, 7.9%-53.0%), and demonstrating responsibility and
      accountability (26%; 95% confidence interval, 2.9%-49.0%). CONCLUSION: A
      multisource feedback intervention positively affected communication skills and
      professional behavior among pediatric residents.

PMID- 17199067
TI  - Parental satisfaction with early pediatric care and immunization of young
      children: the mediating role of age-appropriate well-child care utilization.
AB  - OBJECTIVE: To prospectively evaluate the impact of parental satisfaction on
      childhood immunization and the mediating role of age-appropriate well-child care.
      DESIGN: Secondary analyses of cohort data from the National Evaluation of Healthy
      Steps for Young Children. Data sources included an enrollment questionnaire,
      parent interview at 2 to 4 months, and medical records. SETTING: Twenty-four
      pediatric practices across the United States. PARTICIPANTS: A total of 4896 (85%)
      of the initial 5565 enrolled families who were interviewed at 2 to 4 months and
      had abstracted medical records. MAIN EXPOSURE: Parental satisfaction with overall
      pediatric care assessed at 2 to 4 months as excellent, good, or fair/poor. MAIN
      OUTCOME MEASURES: Age-appropriate first dose of diphtheria-tetanus-pertussis;
      third dose of diphtheria-tetanus-pertussis; and measles, mumps, and rubella
      vaccinations; and up-to-date vaccinations at 24 months (4 diphtheria-tetanus
      pertussis, 3 polio, and 1 measles, mumps, and rubella). RESULTS: The majority of
      parents were satisfied with their child's health care; only 4% rated overall care
      as fair or poor. Children whose parents reported fair/poor satisfaction with care
      had a reduced odds of receiving age-appropriate first dose of diphtheria-tetanus
      pertussis vaccination (odds ratio, 0.43; 95% confidence interval, 0.28-0.67);
      third dose of diphtheria-tetanus-pertussis vaccination (odds ratio, 0.52; 95%
      confidence interval, 0.36-0.74); and measles, mumps, and rubella vaccination
      (odds ratio, 0.58; 95% confidence interval, 0.37-0.92); and of being up to date
      by 24 months (odds ratio, 0.65; 95% confidence interval, 0.43-0.99) compared with
      children whose parents reported excellent care, independent of sociodemographic
      and maternal health care utilization variables. The negative effect of fair/poor
      satisfaction on immunization was largely explained by reduced utilization of age
      appropriate well-child care. CONCLUSION: Quality assurance activities that assess
      parental satisfaction with care may have added value in identifying children who
      are less likely to receive timely preventive services.

PMID- 17199068
TI  - Multimicronutrient supplementation for undernourished pregnant women and the
      birth size of their offspring: a double-blind, randomized, placebo-controlled
      trial.
AB  - OBJECTIVE: To evaluate the effect of multimicronutrient supplementation for
      undernourished pregnant women on the birth size of their offspring, incidence of
      low-birth-weight infants (<2500 g), and early neonatal morbidity. DESIGN:
      Randomized, double-blind, placebo-controlled trial. SETTING: Tertiary care
      hospital. PARTICIPANTS: Two hundred pregnant women (of 13 465 approached) with a
      body mass index (calculated as weight in kilograms divided by the square of
      height in meters) of less than 18.5 and/or a hemoglobin level of 7 to 9 g/dL were
      enrolled at 24 to 32 weeks of gestation. One hundred forty-six neonates (73.0%)
      were available for analysis of birth size and 170 (85.0%) for analysis of
      morbidity in the 7 days after delivery. Intervention The micronutrient
      supplementation group (n = 99) received a multimicronutrient supplement
      containing 29 vitamins and minerals once a day, from enrollment until delivery
      (median duration, 58 days; interquartile range, 37-77 days; compliance, 87%). The
      comparison group (n = 101) received placebo for 52 (15-66) days, with 85%
      compliance. All subjects also received supplements of iron (given in the form of
      ferrous sulfate, containing 60 mg of elemental iron), 60 mg/d, and folic acid,
      500 mug/d. MAIN OUTCOME MEASURES: Birth weight, length, midarm circumference,
      incidence of low birth weight, and early neonatal morbidity. RESULTS: Infants in
      the micronutrient group were heavier by 98 g (95% confidence interval [CI], -16
      to 213 g) and measured 0.80 cm (95% CI, 0.03-1.57 cm) longer and 0.20 cm (95% CI,
      0.04-0.36 cm) larger in midarm circumference compared with the placebo group.
      Incidence of low birth weight declined from 43.1% to 16.2% with
      multimicronutrient supplementation a (a 70% decrease; relative risk, 0.30; 95%
      CI, 0.13-0.71; P=.006), and that of early neonatal morbidity declined from 28.0%
      to 14.8% (a 58% decrease; relative risk, 0.42; 95% CI, 0.19-0.94; P=.04).
      CONCLUSION: Compared with iron and folic acid supplementation, the administration
      of multimicronutrients to undernourished pregnant women may reduce the incidence
      of low birth weight and early neonatal morbidity.

PMID- 17199069
TI  - Effectiveness of child safety seats vs safety belts for children aged 2 to 3
      years.
AB  - OBJECTIVE: To compare the effectiveness of child safety seats and lap-shoulder
      belts in rear passenger vehicle seats for 2- to 3-year-old crash survivors.
      DESIGN: Cohort study. SETTING: The January 1, 1998, to December 31, 2004, US data
      on a nationally representative sample of crashes that resulted in at least 1
      vehicle being towed away. PARTICIPANTS: Toddlers who were sitting in rear vehicle
      seats and using lap-shoulder belts or child seats when involved in highway
      crashes. INTERVENTION: Child safety seat vs safety belt. OUTCOME MEASURE:
      Presence of any injury after a crash. RESULTS: The adjusted odds of injury were
      81.8% lower (95% confidence interval, 58.3%-92.1% lower) for toddlers in child
      seats than belted toddlers. CONCLUSIONS: Child safety seats seem to be more
      effective rear seat restraints than lap-shoulder safety belts for children aged 2
      to 3 years. Laws requiring that children younger than 4 years travel in child
      safety seats have a sound basis and should remain in force.

PMID- 17199071
TI  - A systematic review of school-based interventions to prevent bullying.
AB  - OBJECTIVE: To conduct a systematic review of rigorously evaluated school-based
      interventions to decrease bullying. DATA SOURCES: MEDLINE, PsycINFO, EMBASE,
      Educational Resources Information Center, Cochrane Collaboration, the Physical
      Education Index, and Sociology: A SAGE Full-Text Collection were searched for the
      terms bullying and bully. STUDY SELECTION: We found 2090 article citations and
      reviewed the references of relevant articles. Two reviewers critically evaluated
      56 articles and found 26 studies that met the inclusion criteria. INTERVENTIONS:
      The types of interventions could be categorized as curriculum (10 studies),
      multidisciplinary or "whole-school" interventions (10 studies), social skills
      groups (4 studies), mentoring (1 study), and social worker support (1 study).
      MAIN OUTCOME MEASURES: Data were extracted regarding direct outcome measures of
      bullying (bullying, victimization, aggressive behavior, and school responses to
      violence) and outcomes indirectly related to bullying (school achievement,
      perceived school safety, self-esteem, and knowledge or attitudes toward
      bullying). RESULTS: Only 4 of the 10 curriculum studies showed decreased
      bullying, but 3 of those 4 also showed no improvement in some populations. Of the
      10 studies evaluating the whole-school approach, 7 revealed decreased bullying,
      with younger children having fewer positive effects. Three of the social skills
      training studies showed no clear bullying reduction. The mentoring study found
      decreased bullying for mentored children. The study of increased school social
      workers found decreased bullying, truancy, theft, and drug use. CONCLUSIONS: Many
      school-based interventions directly reduce bullying, with better results for
      interventions that involve multiple disciplines. Curricular changes less often
      affect bullying behaviors. Outcomes indirectly related to bullying are not
      consistently improved by these interventions.

PMID- 17199070
TI  - Differences in neonatal mortality among whites and Asian American subgroups:
      evidence from California.
AB  - OBJECTIVE: To obtain information about health outcomes in neonates in 9 subgroups
      of the Asian population in the United States. DESIGN: Cross-sectional comparison
      of outcomes for births to mothers of Cambodian, Chinese, Filipino, Indian,
      Japanese, Korean, Laotian, Thai, and Vietnamese origin and for births to non
      Hispanic white mothers. Regression models were used to compare neonatal mortality
      across groups before and after controlling for various risk factors. SETTING: All
      California births between January 1,1991, and December 31, 2001. PARTICIPANTS:
      More than 2.3 million newborn infants. MAIN EXPOSURE: Racial and ethnic groups.
      MAIN OUTCOME MEASURE: Neonatal mortality (death within 28 days of birth).
      RESULTS: The unadjusted mortality rate for births to non-Hispanic white mothers
      was 2.0 per 1000. The unadjusted mortality rate for births to Chinese and
      Japanese mothers was significantly lower (Chinese: 1.2 per 1000, P<.001;
      Japanese: 1.2 per 1000, P=.004), and for births to Korean mothers the rate was
      significantly higher (2.7 per 1000, P=.003). For infants of Chinese mothers,
      observed risk factors explain the differences observed in unadjusted data. For
      infants of Cambodian, Japanese, Korean, and Thai mothers, differences persist or
      widen after risk factors are considered. After risk adjustment, infants of
      Cambodian, Japanese, and Korean mothers have significantly lower neonatal
      mortality rates compared with infants born to non-Hispanic white mothers
      (adjusted odds ratios, 0.58 for infants of Cambodian mothers, 0.67 for infants of
      Japanese mothers, and 0.69 for infants of Korean mothers; all P<.05); infants of
      Thai mothers have higher neonatal mortality rates (adjusted odds ratio, 1.89;
      P<.05). CONCLUSIONS: There are significant variations in neonatal mortality
      between subgroups of the Asian American population that are not entirely
      explained by differences in observable risk factors. Efforts to improve clinical
      care that treat Asian Americans as a homogeneous group may miss important
      opportunities for improving infant health in specific subgroups.

PMID- 17199072
TI  - Geographic and occupational risk factors for ventricular septal defects:
      Washington State, 1987-2003.
AB  - OBJECTIVE: Ventricular septal defect (VSD) is currently the most common
      congenital cardiac malformation in the United States, but little is known about
      its etiology. The objective of this study was to address the hypothesis that
      parents' residence in eastern Washington, a region heavily dominated by the
      agricultural industry, and employment in agriculturally related occupations can
      influence the presence of a VSD in their offspring. DESIGN: Population-based case
      control study. SETTING: Washington State from January 1, 1987, through December
      31, 2003. PATIENTS: Children aged 0 to 2 years diagnosed as having a VSD (n =
      3489), and other infants selected at random as control subjects (n = 13 290).
      MAIN EXPOSURES: Parental occupation and county of maternal residence were
      obtained from the birth certificate. The latter was categorized according to
      region (east vs west), rural-urban classification, and the proportion of farm and
      crop land. MAIN OUTCOME MEASURES: Diagnosis of VSD within the first 2 years of
      life. RESULTS: The risk of VSD was greater for infants whose mothers resided in
      eastern Washington (odds ratio, 1.30; 95% confidence interval, 1.03-1.65). The
      risk of VSD with other cardiac malformations (n = 1205) exhibited a stronger
      geographic association than did isolated VSD (n = 2284). Analyses restricted to
      eastern Washington did not reveal a clear relationship between the risk of VSD
      and an increasing proportion of agricultural land in the mother's county of
      residence. Parental occupation in agriculture was not associated with the
      presence of VSD. CONCLUSION: Although these findings suggest regional variation
      in Washington State in the occurrence of VSD, the basis for this variation
      remains to be determined.

PMID- 17199073
TI  - Acute pulmonary infiltrate in a 20-month-old child. Bochdalek diaphragmatic
      hernia.

PMID- 17199074
TI  - Integrated, evidence-based approaches to save newborn lives in developing
      countries.

PMID- 17199075
TI  - Feedback improves performance: validating a first principle.

PMID- 17199076
TI  - Feasibility of a dance videogame to promote weight loss among overweight children
      and adolescents.

PMID- 17199077
TI  - Diphenhydramine in infants.

PMID- 17199078
TI  - Epithelial Na+ channels are fully activated by furin- and prostasin-dependent
      release of an inhibitory peptide from the gamma-subunit.
AB  - Epithelial sodium channels (ENaC) are expressed in the apical membrane of high
      resistance Na(+) transporting epithelia and have a key role in regulating
      extracellular fluid volume and the volume of airway surface liquids. Maturation
      and activation of ENaC subunits involves furin-dependent cleavage of the
      ectodomain at two sites in the alpha subunit and at a single site within the
      gamma subunit. We now report that the serine protease prostasin further activates
      ENaC by inducing cleavage of the gamma subunit at a site distal to the furin
      cleavage site. Dual cleavage of the gamma subunit is predicted to release a 43
      amino acid peptide. Channels with a gamma subunit lacking this 43-residue tract
      have increased activity due to a high open probability. A synthetic peptide
      corresponding to the fragment cleaved from the gamma subunit is a reversible
      inhibitor of endogenous ENaCs in mouse cortical-collecting duct cells and in
      primary cultures of human airway epithelial cells. Our results suggest that
      multiple proteases cleave ENaC gamma subunits to fully activate the channel.

PMID- 17199079
TI  - Association between Helicobacter pylori infection and iron deficiency varies
      according to age in healthy adolescents.

PMID- 17199080
TI  - The effect of dietary habits and socioeconomic status on the prevalence of iron
      deficiency in children of northern Greece.
AB  - BACKGROUND: Despite encouraging reports concerning the declining prevalence of
      iron deficiency, this easily preventable disorder is still an existing problem in
      presumably developed regions. OBJECTIVE: To evaluate the prevalence of iron
      deficiency and relevant anemia in children residing in Northern Greece and to
      study possible associations. DESIGN: 3,100 children aged 8 months to 15 years
      were evaluated. Socioeconomic status was determined based on the parents'
      profession and place of residence. Nutrition habits were also evaluated. RESULTS:
      The incidence of iron deficiency was found to be 14% and that of iron deficiency
      anemia was 2.9%, with a higher prevalence in children younger than 2 years of
      age. The place of residence was the most significant factor in relation to the
      development of iron depletion in the children studied. Additional independent
      factors were revealed to be breast-feeding, meat-containing meal consumption and
      the consumption of non-home-cooked meals. CONCLUSION: Iron deficiency remains
      prevalent in Northern Greece, mainly affecting the vulnerable toddler group.
      Nutritional iron deficiency is still a severe public health problem even in what
      are considered to be developed regions. An improvement of dietary habits and an
      upgrading of semiurban areas should contribute substantially to decreasing the
      prevalence of iron depletion in Greek children.

PMID- 17199081
TI  - A simple method for the estimation of peritoneal fluid transport.
AB  - BACKGROUND: Evaluating peritoneal fluid kinetics is of great value to the
      adjustment of peritoneal dialysis prescription. Therefore, in the present study,
      we developed a simple method, based on a membrane transport model, to evaluate
      the fluid transport characteristics of the peritoneal membrane in continuous
      ambulatory peritoneal dialysis (CAPD) patients. METHODS: Patients' peritoneal
      ultrafiltration (UF) volume was collected for 2 consecutive months. Membrane
      transport model and nonlinear least-squares regression analyses were applied to
      the pooled UF volume for the first month for fluid kinetic simulation and the
      data from the second month were used to evaluate the reliability and precision of
      simulated UF values. RESULTS: Seventeen chronic peritoneal dialysis (PD) patients
      were selected for the present study. Simulated UF values based on the pooled UF
      volume in the first month correlated significantly with the actual measured UF
      values in the second month. By Bland-Atman plot, the width between the 95% limits
      of agreement fell within -133.3 to 154.2 ml with a mean difference of 10.5 ml.
      CONCLUSION: Our study showed that applying the fluid transport model and
      nonlinear least-squares regression analysis to the pooled actual UF value might
      be a good and simple way to predict peritoneal UF.

PMID- 17199082
TI  - Writing good abstracts.
AB  - INTRODUCTION: Writing an abstract means to extract and summarize (AB -
      absolutely, STR - straightforward, ACT - actual data presentation and
      interpretation). Thousands of abstracts are submitted to stroke conferences each
      year. The following suggestions may improve the chances of your work being
      selected for presentation, and to communicate results in the most efficient and
      unambiguous way. TITLE AND STRUCTURE: Make the title dynamic and informative,
      rather than descriptive. Structure the abstract following the IMRaD
      (Introduction, Methods, Results and Discussion) principle for your future
      original paper where background would become Introduction and conclusions would
      enter Discussion. Select the appropriate category for submission carefully. This
      determines which experts grade the abstract and the session where your
      competitors represent their work. If selected appropriately, your abstract is
      more likely to be graded by peers with similar interests and familiarity with
      your work or field. Methods should describe the study design and tools of data
      acquisition shortly, not data. RESULTS: Provide data that answer the research
      question. Describe most important data with numbers and statistics. Make your
      point with data, not speculations and opinions. Abbreviations should be avoided
      and only be used after they have been spelled out or defined. Common mistakes
      include failure to state the hypothesis, rationale for the study, sample size and
      conclusions. Highlight the novelty of your work by carefully chosen
      straightforward wording. CONCLUSIONS: Conclusions have to be based on the present
      study findings. Make sure your abstract is clear, concise and follows all rules.
      Show your draft to colleagues for critique, and if you are not a native English
      speaker show it to a person who can improve/correct your text. Remember that
      accepted abstracts of completed original research should be followed by published
      original papers - if this is not intended or fails, it may indicate an impaired
      ability to succeed in scientific writing and an academic career.

PMID- 17199084
TI  - Anatomic variations in the circle of Willis in patients with symptomatic carotid
      artery stenosis assessed with multidetector row CT angiography.
AB  - PURPOSE: To assess the presence of anterior and posterior collateral pathways in
      the circle of Willis in patients with symptomatic carotid artery stenosis (SCAS)
      and to compare this to patients without carotid artery stenosis. MATERIALS AND
      METHODS: Multislice CT angiography was performed in 91 patients and 91 control
      subjects. Using consensus reading, 2 observers evaluated the presence and
      diameter of the anterior communicating artery (AcomA), the A1 segments of the
      anterior cerebral arteries, the posterior communicating arteries (PcomA) and the
      P1 segments of the posterior cerebral arteries. Anterior or posterior pathways
      were assumed to be present if the diameter of continuous arterial segments was >1
      mm; both A1 segments and AcomA anterior, and ipsilateral P1 segment and PcomA
      posterior. Comparison between patients and controls was performed using the
      chi(2) test. RESULTS: In the patients we found significantly more hypoplastic (<1
      mm) or invisible A1 segments (16 and 14 vs. 4 and 1, respectively, p < 0.01). The
      AcomA was invisible in 4 patients versus 1 control. An isolated compromised
      anterior pathway and a combined compromised anterior and posterior pathway
      occurred more frequently in the patients as compared to the controls; 9 versus 1%
      (p < 0.01) and 26 versus 4% (p < 0.01). CONCLUSION: A compromised anterior
      collateral pathway, usually combined with a compromised posterior pathway, occurs
      more frequently in patients with SCAS as compared to controls, which suggests a
      relation between symptomatic carotid stenosis and an incomplete circle of Willis.

PMID- 17199083
TI  - Elevated troponin levels are associated with sympathoadrenal activation in acute
      ischaemic stroke.
AB  - BACKGROUND: It has been hypothesised that elevated serum troponin levels in acute
      stroke are due to myocardial damage caused by sympathoadrenal activation, which,
      in turn, may be due particularly to insular damage. We aimed to determine the
      factors associated with troponin elevation in ischaemic stroke and the prognostic
      value of this finding. METHODS: We studied 222 consecutive acute ischaemic stroke
      admissions. Serum troponin I and catecholamines were measured. Ischaemic damage
      on brain computed tomography (CT) scan was graded using the Alberta Stroke
      Program Early CT Score (ASPECTS). Electrocardiograms were classified using the
      Minnesota Code and the European Society of Cardiology/American College of
      Cardiology criteria for acute myocardial infarction. The Rankin scale was
      recorded at 30 days. RESULTS: Forty-five patients (20%) had troponin I >0.2
      microg/l. These troponin-positive patients had higher epinephrine levels (median
      0.27 vs. 0.17 nmol/l; p = 0.0002) and were more likely to have electrocardiograms
      coded as definite or possible acute myocardial infarction (odds ratio 3.35; 95%
      CI 1.26-8.93), compared with those with troponin < or = 0.2 microg/l, in
      univariate analysis. There were no significant associations between troponin I
      score and ASPECTS or insular damage on brain CT. In logistic regression analyses,
      elevated troponin was significantly associated with age, elevated serum
      creatinine and epinephrine; however, increased troponin was not an independent
      predictor of death or dependency (Rankin >2) at 30 days. CONCLUSIONS: Raised
      troponin I is associated with elevation of circulating epinephrine in acute
      ischaemic stroke. Activation of the sympathoadrenal system may be an important
      contributor to myocardial damage in these patients. Increased troponin is not
      associated with insular damage and does not independently predict poor outcome.

PMID- 17199085
TI  - Microembolic signals within 24 hours of stroke onset and diffusion-weighted MRI
      abnormalities.
AB  - BACKGROUND: The clinical relevance of the microembolic signals (MES) detected by
      transcranial Doppler sonography (TCD) in acute stroke remains unclear. In a
      prospective study the authors analyzed the relationship between MES and the
      findings on diffusion-weighted magnetic resonance imaging (DWI) in acute stroke
      patients. METHODS: We performed TCD for a period of 30 min to detect MES in
      patients within 24 h of stroke onset, and DWI was done within the initial 7 days.
      MES were assessed from Doppler waves obtained from the middle cerebral artery
      contralateral to the side of the neurological deficits. The acute ischemic
      lesions observed on DWI were classified by their diameter (small, medium or
      large) and by their site (cortical, superficial perforator territory, internal
      borderzone or deep perforator territory). RESULTS: We obtained Doppler waves from
      39 vessels in 37 patients; 2 patients had bilateral deficits. MES were detected
      in 12 vessels (MES-positive group) and not detected in 27 vessels (MES-negative
      group). No significant differences in clinical features were observed between the
      2 groups. The number of small lesions was significantly higher in the MES
      positive group than in the MES-negative group (p = 0.02). The numbers of cortical
      and superficial perforator infarcts were significantly higher in the MES-positive
      group than in the MES-negative group (p = 0.002 and 0.02, respectively).
      CONCLUSION: In acute ischemic stroke, MES detected by TCD in the acute phase may
      produce small cortical and subcortical lesions found on DWI.

PMID- 17199086
TI  - Improved time intervals by implementation of computerized physician order entry
      based stroke team approach.
AB  - BACKGROUND: The need for rapid evaluation and treatment of acute stroke patients
      has been well documented. A computerized physician order entry (CPOE) system can
      improve communication and provide immediate access to information, which may be
      useful for an effective team approach program targeted to reduce in-hospital time
      delays. METHODS: To reduce the time from a patient's arrival at the emergency
      department to thrombolysis, a team approach program using CPOE was developed, and
      its efficacy was investigated by comparing time intervals from arrival to
      evaluation and intravenous tissue-type plasminogen activator (tPA) treatment
      before and after the implementation of the program. RESULTS: Among 379
      consecutive patients who were screened as potential candidates for thrombolysis,
      25 patients (6.6%) received tPA during a 1-year period after initiation of the
      program. Fourteen patients were treated with tPA in the previous year. After
      program implementation, time from arrival to computed tomography scan was reduced
      from 34 to 19 min (p = 0.01). Time to report of complete blood count was also
      shortened from 52 to 33 min (p < 0.01). Finally, time from arrival to tPA
      treatment was reduced by 23 min (from 79 to 56 min; p < 0.01). Onset-to-door time
      tended to be longer after the program implementation (from 41 to 60 min; p =
      0.14). CONCLUSIONS: Implementation of the CPOE-based team approach program
      significantly reduced time from emergency department arrival to evaluations and
      treatment.

PMID- 17199087
TI  - Estimating the number of stroke patients eligible for thrombolytic treatment if
      delay could be avoided.
AB  - BACKGROUND: Although no data are available on the potential number of patients
      treatable with recombinant tissue plasminogen activator, it is said that up to
      20% of all stroke patients should receive this treatment. The actual percentage
      treated is much lower, mainly due to delays between onset and admission to
      hospital. The aim of this study was to estimate the potential number of patients
      eligible for thrombolytic therapy if such delays could be avoided. METHODS: We
      gathered data on the time of onset, presentation and admission of stroke
      patients. Based on the inclusion and exclusion criteria for thrombolysis derived
      from the National Institute of Neurological Disorders and Stroke study, we
      retrospectively estimated the number of patients that would have been eligible
      for thrombolytic therapy. RESULTS: A total of 263 consecutive patients were
      included. Forty-eight patients (18%) had symptoms upon awakening, 28 (11%)
      reported their symptoms at a routine follow-up visit and 19 (7%) received
      thrombolytic therapy. All these cases were excluded. If no delay had occurred, an
      additional 44 patients (17%) could have been offered thrombolytic therapy. This
      potential loss of treatable patients was due to patient and doctor delay in 39
      and 2 patients, respectively, and to other reasons in 3 patients. CONCLUSION: Up
      to 24% of stroke patients are eligible for thrombolytic treatment if delay is
      avoided. As delays are mainly caused by patients themselves, the results of this
      study underline the need for campaigns to improve the public's awareness of
      stroke symptoms as well as the awareness that stroke is an emergency situation.

PMID- 17199088
TI  - Do extracellular-matrix-regulating enzymes play a role in cervical artery
      dissection?
AB  - BACKGROUND: An underlying extracellular matrix defect is suspected in patients
      with spontaneous cervical artery dissection (SCAD). We test the hypothesis that
      levels of matrix metalloproteinase (MMP) 2 and 9, and elastase, extracellular
      matrix-regulating enzymes involved in the vascular wall remodeling process, are
      modified in SCAD. METHODS: The authors prospectively and consecutively recruited
      47 patients with SCAD and 52 patients with an ischemic stroke from another cause
      in 2 centers, and measured their plasmatic level of MMP-2, MMP-9 and elastase 3
      months after the vascular event. RESULTS: Patients with SCAD had a higher mean
      MMP-2 level compared with controls [379.2 (SD = 76.6) vs. 355.9 (75.1) ng/ml; p =
      0.11] and had more frequently a high level of MMP-2 (>326 ng/ml) than controls
      (77.8 vs. 54.5%, p = 0.019). This association was stronger in patients with
      multiple dissection than single artery dissection or controls (84.6, 75.0 and
      54.5%, respectively, p = 0.018). The levels of MMP-9 and elastase were similar in
      cases and controls, but more patients had a high level of these enzymes in the
      group with multiple dissections than in the group with single artery dissection
      or controls. CONCLUSION: Patients with SCAD have higher plasma levels of
      proteases, particularly MMP-2. The association is stronger in patients with
      multiple dissections.

PMID- 17199090
TI  - sCD40 ligand determined in maternal and umbilical cord blood in pregnancies
      complicated by pre-eclampsia with and without intrauterine growth retardation.
AB  - OBJECTIVE: The aim of this study was determination and comparative analysis of
      the maternal and umbilical cord sCD40L serum levels in pregnancies complicated by
      pre-eclampsia with and without intrauterine growth retardation (IUGR) and in
      normotensive pregnancies. PATIENTS AND METHODS: The study was carried out on 16
      patients with singleton pregnancies complicated by severe pre-eclampsia with
      appropriate-for-gestational-age weight infants and 14 pregnant patients with
      severe pre-eclampsia complicated by IUGR. The control group consisted of 13
      healthy normotensive delivering patients. Five milliliters of blood were taken by
      venipuncture from each pre-eclamptic patient and from each woman from the control
      group before active phase of labor and 5 ml of umbilical vein blood were taken
      immediately after delivery and collected in sterile tubes. Maternal and umbilical
      serum sCD40L concentrations were estimated using a sandwich ELISA assay. RESULTS
      AND CONCLUSIONS: Our results reveal the higher levels of maternal and umbilical
      sCD40L serum levels in pregnancy complicated by pre-eclampsia with and without
      IUGR. The mean maternal values were 4.022 +/- 2.399 ng/ml in group P, 3.914 +/-
      2.824 ng/ml in group PI and 0.885 +/- 0.064 ng/ml in healthy controls. The mean
      umbilical values were 2.633 +/- 1.984 ng/ml in group P, 2.703 +/- 1.996 ng/ml in
      group PI and 1.112 +/- 0.436 ng/ml in the control group. It seems that these
      higher concentrations of sCD40L protect maternal immune cells bearing CD40
      receptor from Fas-mediated apoptosis. Our findings may suggest also enhanced
      platelet activation in pre-eclamptic patients. It may be one of the factors
      responsible for the enhanced procoagulatory and proinflammatory properties, and
      increased cytokine production, and endothelial cell dysfunction in pregnancies
      complicated by pre-eclampsia.

PMID- 17199089
TI  - Acute stroke management in the elderly.
AB  - BACKGROUND AND PURPOSE: Though the proportion of elderly stroke patients is
      increasing, patients >80 years are often excluded from clinical stroke trials. We
      reviewed the management of older patients presenting with acute ischemic stroke
      (AIS) and assessed the safety and efficacy of recombinant tissue plasminogen
      activator (rtPA) administration in a community-based setting. METHODS: A
      retrospective review of patients >80 years (n = 341) admitted to a community
      stroke center with AIS were compared to their younger counterparts (n = 690)
      using the stroke center database from April 2003 to December 2005. Parameters
      that were measured included admission and discharge NIH Stroke Scale (NIHSS),
      rate of thrombolytic treatment, the frequency and etiology of thrombolytic
      exclusion criteria and complications from rtPA for the different aged
      populations. Additional data were collected for Barthel Index at 12 months.
      RESULTS: A total of 166 patients underwent thrombolysis. Older patients were not
      delayed in reaching the hospital within 3 h of stroke onset (182/690, 26%, in the
      <80 cohort vs. 98/341, 29%, in the > or = 80 cohort). Although the overall rates
      of tPA use were similar in both the young and aged cohort, older patients were
      less likely to be treated with rtPA because of reasons not listed as exclusion
      criteria (17% in the <80 cohort vs. 32% in the > or = 80 cohort). The older group
      did not have an excess risk of intracranial hemorrhage following rtPA infusion
      despite equivalent NIHSS on admission (13.5 in the <80 cohort vs. 12.4 in the >
      or = 80 cohort). Both groups showed improvement in NIHSS following thrombolytic
      treatment with a drop of 7.7 points in the younger age group and 5.6 points in
      the older group. Elderly patients treated with rtPA had a comparable 12-month
      modified Barthel Index score to younger cohorts. CONCLUSIONS: Early treatment
      with rtPA in patients >80 years appears to be both safe and efficacious. Treated
      patients showed improvements both acutely (a decrease in NIHSS at 72 h) and
      chronically, as shown by a sustained improvement in the Barthel Index. A large
      number of elderly patients were excluded from rtPA treatment despite arriving
      within the time frame of treatment for reasons not considered as traditional
      exclusion criteria. Older patients with AIS can be treated safely with
      thrombolytic therapy in a community setting. This therapy should not be withheld
      on the basis of age.

PMID- 17199091
TI  - Proteomic analysis of proteins differentially expressed in preeclamptic
      trophoblasts.
AB  - AIMS: To identify differential trophoblastic proteins associated with
      preeclampsia (PE) by proteomic analysis. METHODS: We isolated and purified
      placental trophoblasts from normotensive pregnant women and patients with PE by a
      continuous Percoll gradient. The expression of proteins was determined by sliver
      staining after two-dimensional polyacrylamide gel electrophoresis (2D-PAGE).
      Proteins of interest were identified using matrix-assisted laser desorption
      ionization time of flight mass spectrometry (MALDI-TOF-MS). RESULTS: The overall
      trophoblastic protein expression patterns in preeclamptic and corresponding
      normotensive placentas were quite similar except for some areas. Of 34
      differentially expressed protein spots (p < 0.05 by paired t-test), seven
      differential proteins from nine spots were identified by MALDI-TOF-MS. The
      expression of the following proteins was repressed (p < 0.01): disulfide
      isomerase ER-60, peroxiredoxin 2, and Delta3,5-Delta2,4-dienoyl-CoA isomerase.
      Four proteins (protein disulfide isomerase precursor, endoplasmic reticulum
      resident protein, dihydrolipoyl dehydrogenase and TIM21-like protein) were found
      to be significantly upregulated in PE (p < 0.01). CONCLUSION: We identified
      several proteins with significant altered expression in PE using 2D-PAGE. This
      method is a powerful technique with which to search for not only quantitative but
      also qualitative changes in a biological process of interest.

PMID- 17199092
TI  - How many deaths can be prevented by newborn screening for congenital adrenal
      hyperplasia?
AB  - BACKGROUND/AIMS: Congenital adrenal hyperplasia (CAH) is increasingly being
      included in newborn screening programs. Screening can prevent neonatal mortality
      in children with salt-wasting CAH, but the number of deaths prevented is not
      known. Cost-effectiveness analyses of screening require estimates of the
      probability of mortality in CAH. METHODS: We reviewed the literature to identify
      cohort studies of children with CAH ascertained clinically in the absence of
      screening. We abstracted the numbers of infant deaths attributable to CAH. We
      also addressed sex ratios among children with clinically detected CAH and the
      contribution of ascertainment bias to unbalanced ratios. RESULTS: The evidence
      suggests a probability of infant death due to adrenal crises in salt-wasting CAH
      of 4% or less in contemporary advanced economies without screening for CAH. This
      is lower than previous estimates, although the rate of mortality could be
      considerably higher in populations with limited clinical awareness or access.
      CONCLUSION: Although screening for CAH is conducted in a number of countries,
      further research is still needed to provide reliable estimates on the numbers of
      prevented deaths, along with evidence-based assessments of the potential
      benefits, harms, and costs of screening.

PMID- 17199093
TI  - Effects of probiotics on allergic rhinitis induced by Japanese cedar pollen:
      randomized double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Lactobacillus casei strain Shirota (LcS) has been found to exert
      antiallergic effects in animal experiments, but there is little information about
      its clinical effects in human patients with allergy. METHODS: We performed a
      randomized double-blind, placebo-controlled study to investigate the effects of
      LcS in patients with allergic rhinitis triggered by Japanese cedar pollen (JCP).
      Participants were asked to drink fermented milk containing LcS (LcS group) or
      placebo (control group) for 8 weeks. Clinical symptoms and immunological
      parameters were compared between the two groups. RESULTS: Symptom-medication
      scores (SMS) worsened in accordance with the increase in the amount of scattered
      JCP. In terms of the nasal and ocular SMS, there was no significant difference
      between the LcS group and the placebo group during the ingestion period. In the
      subgroup of patients with moderate-to-severe nasal symptom scores before starting
      the ingestion of test samples, supplementation with LcS tended to reduce nasal
      SMS. CONCLUSION: These results indicate that fermented milk containing LcS does
      not prevent allergic symptoms in patients sensitive to JCP, but may delay the
      occurrence of allergic symptoms in patients with moderate-to-severe nasal symptom
      scores.

PMID- 17199094
TI  - Effects of diabetes mellitus, chronic renal failure and hemodialysis on serum and
      salivary antioxidant status.
AB  - AIM: To analyze various oxidative stress parameters in the saliva and serum of
      patients with chronic renal failure (CRF) and/or diabetes mellitus (DM), and to
      compare them in dialytic vs. pre-dialytic patients. METHOD: 50 consenting
      patients were divided into five subgroups of patients: severe CRF (dialytic)
      without DM, severe CRF (dialytic) with DM, mild CRF (pre-dialytic) without DM,
      mild CRF (pre-dialytic) with DM, and with DM but without CRF (controls). Uric
      acid (UA), peroxidase and total antioxidant status (TAS) were studied in both
      saliva and serum; superoxide dismutase (SOD) was evaluated only in saliva. Both
      saliva collection and serum harvesting were done simultaneously. RESULTS: In
      severe-CRF patients without DM, median TAS, UA and SOD levels decreased following
      dialysis (54, 85, 48%, respectively), and peroxidase levels increased slightly
      (9%). In severe-CRF patients with DM, median TAS and SOD levels increased
      following dialysis (33 and 54%, respectively) while median UA and peroxidase
      levels decreased (68 and 10%, respectively). CONCLUSIONS: DM, CRF and
      hemodialysis were found to increase the oxidative stress burden in both serum and
      saliva. Therefore, antioxidant assessment may be used to monitor baseline
      oxidative status in these situations though larger randomized studies are in
      order.

PMID- 17199095
TI  - Angiotensin II receptor blockade ameliorates mesangioproliferative
      glomerulonephritis in rats through suppression of CTGF and PAI-1, independently
      of the coagulation system.
AB  - BACKGROUND: Previously we observed that the coagulation system promotes matrix
      protein accumulation through transforming growth factor (TGF)-beta and connective
      tissue growth factor (CTGF) expression in rat mesangioproliferative
      glomerulonephritis (MsPGN). Angiotensin II receptor blockers (ARBs) are known to
      suppress matrix accumulation in experimental MsPGN. In the present study, we
      investigated whether ARB suppresses MsPGN through inhibition of these profibrotic
      cytokines, and in relation to coagulation and fibrinolytic systems. METHODS:
      MsPGN was induced in Wistar rats by intravenous injection of anti-Thy-1.1
      monoclonal antibody, OX-7. As an ARB, olmesartan was orally administered in rat
      feed from the day of OX-7 injection (day 0) to day 8, when rats were sacrificed
      and kidney specimens were collected. The degrees of cellular proliferation,
      matrix production, coagulation factors, and inhibitory factor of fibrinolysis
      were evaluated. RESULTS: Although blood pressure did not change in the normal,
      disease control, or treatment groups, the amount of urinary protein was
      significantly decreased in the ARB-treated groups, compared with the disease
      control group (p < 0.05). alpha-Smooth muscle actin expression was suppressed
      significantly in the treatment groups (p < 0.001). Blue-staining areas of
      trichrome, the number of proliferating cell nuclear antigen (PCNA)- or ED-1
      positive cells, fibronectin and plasminogen activator inhibitor type 1 in
      glomeruli significantly decreased in the treatment groups (p < 0.05,
      respectively); however, fibrin-related antigen and factor V depositions were not
      suppressed in the treatment groups. CONCLUSIONS: These results suggest that the
      ARB drug would ameliorate MsPGN in vivo, at least partly through CTGF and
      plasminogen activator inhibitor type 1 suppression, and independently of the
      local coagulation system in glomeruli.

PMID- 17199096
TI  - Facial expressions and personality: a kinematical investigation during an emotion
      induction experiment.
AB  - BACKGROUND/AIMS: In order to elucidate the relationship between personality
      traits and expression of positive emotions in healthy volunteers, standardized
      personality inventories and kinematical analysis of facial expressions can be
      helpful and were applied in the present study. METHODS: Markers fixed at distinct
      points of the face emitting ultrasonic signals at high frequency gave a direct
      measure of facial movements with high spatial-temporal resolution. Forty-six
      healthy participants (mean age: 40.7 years; 20 males, 26 females) watching a
      witty movie ("Mr. Bean") were investigated. RESULTS: Speed of "laughing" was
      associated with higher scores on Zuckerman's Sensation Seeking Scale and NEO-FFI
      (Openness to Experience). CONCLUSION: Kinematical analysis of facial expressions
      seems to reflect sensation seeking and related personality styles. Higher speed
      of facial movements in sensation seekers suggests lowered serotonergic function.

PMID- 17199097
TI  - Asymmetrically altered integrity of cingulum bundle in posttraumatic stress
      disorder.
AB  - Previously, our group reported the altered white matter tract integrity of the
      left anterior cingulate in posttraumatic stress disorder (PTSD) in whole-brain
      exploration. Current study intended to explore whether the alteration was more
      prominent in any specific regions of the cingulum bundle. Diffusion tensor images
      of 21 PTSD subjects and 21 healthy comparison subjects were acquired. Eight
      isocubic regions of interest (ROIs), i.e. bilateral rostral, subgenual, dorsal,
      and upper cingulum bundle, were selected. Fractional anisotropy values in each
      ROI, which indicate the white matter tract integrity, were measured and compared
      between groups. Relative to comparison subjects, PTSD subjects had significantly
      smaller fractional anisotropy values in the left side of rostral, subgenual and
      dorsal cingulum bundle (26.7, 25.0, 22.2% decrease, respectively), but not in the
      right side ROIs. We report an asymmetrical alteration of the cingulum bundle in
      PTSD.

PMID- 17199098
TI  - Effects of caffeine on electrophysiological and neuropsychological indices after
      sleep deprivation.
AB  - Caffeine is regarded as a central nervous system (CNS) stimulant. The goal of
      this study was to analyze electrophysiological, motor, cognitive and behavioral
      changes produced by caffeine ingestion after sleep deprivation. Ten subjects were
      evaluated after sleep deprivation, comparing the ingestion of either 400 mg of
      caffeine or placebo, in a double-blind randomized study. The variables analyzed
      were: quantitative EEG, the event-related potential (ERP-P300) and cognitive
      responses. The most significant quantitative EEG results, which were
      characterized by moment x treatment interactions, were seen in alpha and theta
      relative power variables. A significant decrease in relative alpha and theta was
      observed in the caffeine group after sleep deprivation. In relation to caffeine
      stimulant effects, there were no significant differences in the other parameters.

PMID- 17199099
TI  - Increased omega complexity and decreased microstate duration in nonmedicated
      schizophrenic patients.
AB  - To explore brain functions in schizophrenic patients, the global analytic
      strategy of multichannel EEG was performed that combines measures of global
      complexity (Omega), total power (Sigma) and generalized frequency (Phi), and EEG
      microstate analysis was applied to multichannel EEG data for 24 nonmedicated
      patients and 24 healthy subjects. The patients had higher Omega and Sigma values,
      and lower Phi values compared with healthy subjects. Three topographical classes
      were obtained from all EEG data by EEG microstate analysis. The mean duration of
      one topographical class in the patients was shortened compared to healthy
      subjects. These results indicated looser cooperativity, or decreased connectivity
      of the active brain process and deviant brain information processing in
      schizophrenic patients.

PMID- 17199100
TI  - Autumn peak in shooting suicides of children and adolescents from northern
      Finland.
AB  - Suicide is one of the leading causes of death among adolescents worldwide.
      Studies on the seasonal pattern of youth suicides are rare and the results are
      very contradictory and heterogeneous. Generally, suicide methods affect the
      pattern of suicide seasonality. Shooting is the most common suicide method among
      Finnish adolescents. We investigated whether shooting suicides of victims aged
      less than 18 years are correlated with a specific period of the year. Also, the
      seasonal pattern of shooting suicides in adolescents was compared with that of
      adult victims. Our data comprised 42 adolescent suicide victims and, for
      comparison, 1,926 adult suicide victims over the years 1988 to 2004 from Northern
      Finland. Of these, 59.5% (n = 25) of the adolescents and 28.8% (n = 554) of the
      adults had committed suicide by shooting. We observed that shooting suicides
      among the under-aged showed a significant peak in autumn (ratio 2.70, 95% CI:
      1.97-3.42), while those of adult victims peaked in spring (ratio 1.19, 95% CI:
      1.05-1.35). The monthly pattern of suicides correlated significantly with the
      mean duration of daily sunshine hours (trailing by 3 months) in the under-aged (r
      = 0.67, p = 0.016), but not in the adults (r = 0.06, p = 0.854). The role of
      firearm availability, psychosocial factors such as start of the school year, and
      some biological factors are discussed.

PMID- 17199102
TI  - [Chlamydophila pneumoniae biotype TWAR: selected details].
AB  - Chlamydophila pneumoniae biotype TWAR is classified in the Chlamydiacea family
      and used to be considered a cause of pneumonia. Lately it has been also proved
      that it can cause heart disease and diseases of the blood vessels and also take
      part in the pathogenesis Alzheimer and multiple sclerosis, which shows that
      biotype TWAR has expanded its spectrum.

PMID- 17199101
TI  - [Factor VIII and the risk of arterial thrombosis].
AB  - The pathomechanism of acute complications of atheromatosis, i.e. arterial
      thrombosis, still remains unclear. Conventional cardiovascular risk factors can
      explain only about 50% of cases of arterial thrombosis. The activation of
      intrinsic and extrinsic pathways of the coagulation system on damaged
      atherosclerotic plaque is one of the most important mechanisms. The role of
      clotting factors in the development of arterial thrombosis is also considered.
      From among a few clotting factors (V, VIII, XIII), factor VIII arouses interest
      due to the well-known observation that the morbidity for cardiovascular reasons
      is less among hemophiliacs than in the general population. A high factor VIII
      level predicts the occurrence of episodes of venous thromboses, but its role in
      the pathogenesis of arterial thromboses is still unclear. In clinical studies, a
      high factor VIII level predicts episodes of stroke, myocardial infarct, and acute
      lower-limb ischemia over a short period of observation. A high factor VIII level
      may the cause of about 5% of all episodes of arterial thrombosis. The reasons for
      elevated factor VIII levels in some persons remain unclear. Although heritability
      can play an important role, the influence of other factors (e.g. activation of
      the sympathetic nervous system) has been reported. The pathomechanism is the
      subject of investigation as well. An explanation for the occurrence of severe
      complications of arterial thrombosis in patients without significant risk factors
      may result in the development of methods of detection and prevention.

PMID- 17199103
TI  - [The role of oxidative stress in the etiopathogenesis of rheumatoid arthritis].
AB  - Numerous scientific investigations confirmed the occurrence of oxidative stress
      in rheumatoid arthritis patients. There is evidence demonstrating elevated levels
      of oxidative stress markers and oxidative damage caused by reactive oxygen
      species (ROS) to lipids, proteins, sugars, and DNA, as well as a significant
      decrease in total antioxidant capacity, which protects the organism against ROS
      activity. Extensive ROS production can significantly accelerate the process of
      articular cartilage damage. It is believed that many disease-modifying anti
      rheumatic drugs (DMARDs) affect oxidative stress, although there has been
      insufficient research to confirm such a relationship.

PMID- 17199105
TI  - NT-proBNP levels correlate with organ failure in septic patients: a preliminary
      report.
AB  - The aim of the study was to evaluate the relationship between N-terminal brain
      natriuretic propeptide (NT-proBNP) plasma concentrations and the severity of
      organ dysfunction assessed by the Sepsis-related Organ Failure Assessment (SOFA)
      score in septic patients MATERIAL/METHODS: NT-proBNP, SOFA score, and survival
      were evaluated in 20 consecutive septic patients. They were prospectively
      included in the study when the sepsis criteria according to the ACCP/SCCM
      definitions (modified by the Polish Working Group for Sepsis) were fulfilled.
      Blood serum NT-proBNP concentrations were determined in each patient at given
      time intervals and the severity of organ dysfunction was estimated according to
      the SOFA score. The first measurement was performed within 12 h after the
      patient's inclusion into the study, the second, third, and fourth at 12, 24, and
      48 hours after the first, and then every 48 hours thereafter RESULTS: The mean NT
      proBNP concentration and the mean SOFA score were 140.80+/-84.65 pg/ml and 6.31+/
      3.75 points, respectively. The correlation coefficient between NT-proBNP level
      and SOFA score was R=0.5164 (p<0.05). The mortality in the studied group was 30%.
      CONCLUSIONS: NT-proBNP levels correlate with the severity of organ dysfunction as
      assessed by the SOFA score in septic patients.

PMID- 17199104
TI  - [Selenium and cardiovascular disease: selected issues].
AB  - The paper presents current knowledge of the role of selenium in the development
      of cardiovascular system disease (CSD). Already known mechanisms of selenium
      action in the cardiovascular system are described, whilst underlining the fact
      that they do not explain all relevant observations and need to be clarified by
      more studies. Clinical, epidemiological, and experimental studies devoted to the
      relationship between the progression of CSD and selenium status indices are then
      reviewed. It could be expected that any explanation of the pathophysiological
      mechanisms of the influence of tobacco smoking (as one of the classical risk
      factors for CSD) on selenium status might help to bring about a better
      understanding of the progression of cardiovascular disorders. Based on studies
      conducted on animal models, the role of selenium in the antioxidant defense of
      cardiac muscle is described. Particular attention is paid to a dilated
      cardiomyopathy known as Keshan disease, for which it has been shown that selenium
      deficiency is an environmental factor predisposing to the onset of this disease.
      Similar symptoms of cardiomyopathy are also observed in patients on total
      parenteral nutrition and patients with AIDS.

PMID- 17199106
TI  - [Retroviruses-derived sequences in the human genome. Human endogenous
      retroviruses (HERVs)].
AB  - Retroviruses-derived elements in the human genome constitute 90% of non-coding
      mobile sequences. Reverse transcriptase (RT) plays an essential role in their
      transposition as do long terminal repeats (LTRs), which contain promotors,
      enhancers, and regulatory sequences. Some retroelements (pseudogens and
      retrogenes, e.g. SINE) are non-autonomic and do not possess their own RT. These
      elements are dependent on autonomic elements (retroposons, e.g. LINE,
      retrotransposons, exo- and endogenous retroviruses). The genome of retroviruses
      is composed of gag, pol, and env genes flanked by long terminal repeats.
      Endogenous retroviruses are probably the remnants of ancient germ cell infection
      by exogenous retroviruses and are transmissible to the next generation in a
      Mendelian way. Most of them are defective (because of mutation accumulation), but
      some are still active and their expression is regulated by different factors (UV
      radiation, inflammatory cytokines, steroid hormones, and exogenous virus
      products). Retroelements as well as their gene products exert influence on the
      organism's functions. They influence the plasticity and evolution of genomes, are
      a source of promotors and regulatory sequences, but they also supply additional
      signals of transcription initiation, mRNA splicing, and STOP codons. One of the
      positive aspects of human endogenous retroviruses (HERVs) is the participation of
      their products in normal syncytiotrophoblast formation. They also block exogenous
      retrovirus replication by receptor interference or antisense mRNA. Their presence
      is considered to be connected with a number of autoimmunological diseases
      (multiple sclerosis, insulin-dependent diabetes mellitus, systemic lupus
      erythematosus), cancer, or even psychiatric disorders (schizophrenia). There are
      also other problems connected with the potential role of ERVs in genomic therapy
      (with retroviruses vectors) and transplantology (xenotransplantation).

PMID- 17199107
TI  - [The role of the pineal gland and melatonin in the regulation of adenohypophysial
      hormone synthesis and secretion].
AB  - This paper reviews findings accumulated on the role of the pineal gland and its
      hormone,melatonin, in the regulation of hypothalamo-adenohypophysial system
      activity. The effect of melatonin on somatotrophin (GH), thyreotrophin (TSH), and
      adrenocorticotrophin (ACTH) synthesis and secretion is considered. Results of in
      vivo and in vitro experiments show that the influence of melatonin on
      adenohypophysial activity depends on the animal species, age, sex, the
      concentration of the hormone, and the experimental conditions. Melatonin modifies
      adenohypophysial hormone synthesis and secretion either directly by influencing
      the secretory activity of the cells in the anterior pituitary or indirectly by
      influencing the hypothalamic neurons producing the respective neurohormones which
      stimulate or inhibit the release of adequate adenohypophysial hormones. Melatonin
      acts via specific membrane receptors which have been demonstrated in several
      brain areas, with high concentrations in the hypothalamic suprachiasmatic nucleus
      and the pars tuberalis of the pituitary. It may also act directly on a genome.
      Moreover, the response of the hypothalamo-adenohypophysial system to melatonin
      may depend on this hormone's influence on the metabolism of some neuromediators
      and/or neuromodulators in the central nervous system.

PMID- 17199108
TI  - Mitochondrial rRNA and tRNA and hearing function.
AB  - The human ear is a delicate sensory apparatus of hearing for normal
      communication, and its proper functioning is highly dependent on mitochondrial
      oxidative phosphorylation. The first mitochondrial point mutation for
      nonsyndromic and aminoglycoside-induced hearing loss was identified in 1993.
      Since then a number of inherited mitochondrial mutations have been implicated in
      hearing loss. Most of the molecular defects responsible for mitochondrial
      disorder-associated hearing loss are mutations in the 12S rRNA gene and tRNA
      genes. In this review, after a short description of normal hearing mechanisms and
      mitochondrial genetics, we outline the recent advances that have been made in the
      identification of deafness-associated mitochondrial mutations, and discuss how
      mitochondrial dysfunction contributes to hearing loss.

PMID- 17199109
TI  - The Drosophila ovary: an active stem cell community.
AB  - Only a small number of cells in adult tissues (the stem cells) possess the
      ability to self-renew at every cell division, while producing differentiating
      daughter cells to maintain tissue homeostasis for an organism's lifetime. The
      Drosophila ovary harbors three different types of stem cell populations (germline
      stem cell (GSC), somatic stem cell (SSC) and escort stem cell (ESC)) located in a
      simple anatomical structure known as germarium, rendering it one of the best
      model systems for studying stem cell biology due to reliable stem cell
      identification and available sophisticated genetic tools for manipulating gene
      functions. Particularly, the niche for the GSC is among the first and best
      studied ones, and studies on the GSC and its niche have made many unique
      contributions to a better understanding of relationships between stem cells and
      their niche. So far, both the GSC and the SSC have been shown to be regulated by
      extrinsic factors originating from their niche and intrinsic factors functioning
      within. Multiple signaling pathways are required for controlling GSC and SSC self
      renewal and differentiation, which provide unique opportunities to investigate
      how multiple signals from the niche are interpreted in the stem cell. Since the
      Drosophila ovary contains three types of stem cells, it also provides outstanding
      opportunities to study how multiple stem cells in a given tissue work
      collaboratively to contribute to tissue function and maintenance. This review
      highlights recent major advances in studying Drosophila ovarian stem cells and
      also discusses future directions and challenges.

PMID- 17199110
TI  - 3D computation modelling of the influence of cytokine secretion on Th-cell
      development suggests that negative selection (inhibition of Th1 cells) is more
      effective than positive selection by IL-4 for Th2 cell dominance.
AB  - Th-cell development has been suggested to include selective mechanisms in which
      certain cytokines select either Th1 or Th2 cells to proliferate and grow. The
      selective theory is based on the observation that Th2 cells secrete IL-4, a
      cytokine that promotes Th2 development, whereas Th1 cells secrete interferon
      gamma (IFN-gamma) that favours Th1 development, and both positive and negative
      selective influences have been suggested to operate. In this study, we
      investigate the role of autocrine secretion and utilization of IL-4 by Th2 cells
      and address the question of whether an activated Th2 cell can be positively
      selected by IL-4 secreted from other Th2 cells. We present a spatial three
      dimensional (3D) modelling approach to simulate the interaction between the IL-4
      ligand and its IL-4 receptors expressed on discrete IL-4 secreting cells. The
      simulations, based on existing experimental data on the IL-4 receptor-ligand
      system, illustrate how Th-cell development is highly dependent on the distance
      between cells that are communicating. The model suggests that a single Th2 cell
      is likely to communicate with possible target cells within a range of
      approximately 100 microm and that an activated Th2 cell manages to fill most of
      its own IL-4 receptors, even at a low secretion rate. The predictions made by the
      model suggest that negative selection against Th1 cells is more effective than
      positive selection by IL-4 for promoting Th2 dominance.

PMID- 17199111
TI  - Defining target antigens for CD25+ FOXP3 + IFN-gamma- regulatory T cells in
      chronic hepatitis C virus infection.
AB  - The mechanism behind the apparent lack of effective antiviral immune responses in
      chronic hepatitis C virus (HCV) patients is poorly understood. It remains unclear
      if natural regulatory T cells (Treg) contribute to the induction and maintenance
      of HCV persistence. We herein report for the first time that CD25(high)IFN-gamma(
      )FOXP3(high) Tregs can be rapidly induced by culturing peripheral blood
      mononuclear cells (PBMCs) of HCV-positive patients with HCV protein-derived
      peptides. The HCV-specific Tregs, generally CD4(+)CD45RO(+), did not proliferate
      in response to HCV peptide and failed to produce interferon (IFN)-gamma, in
      distinct contrast to antiviral effector cells. Stimulation of healthy donor PBMCs
      with HCV peptides did not result in CD25 and FOXP3 upregulation above non-antigen
      background. To further investigate the antigen specificity of these potentially
      disease-associated natural Tregs, CD25(+) cells were isolated from PBMCs, labeled
      with carboxyfluorescein diacetate succinimidylester and added back to CD25
      depleted PBMCs, and the co-cultures were then stimulated with individual peptides
      derived from the HCV core protein. We found that the actual peptide that can
      stimulate Treg varied between patients, but within any given subject only a small
      number of the peptides were able to stimulate Treg, suggesting the existence of
      dominant Treg epitopes. Although functional experiments for these peptides are
      ongoing in our laboratory, data presented here suggests that HCV-specific natural
      Tregs are abundant in infected individuals, in contrast to the extremely low
      frequency of anti-HCV effector T cells, supporting the view that natural Treg may
      be implicated in host immune tolerance during HCV infection.

PMID- 17199113
TI  - The best is yet to come.

PMID- 17199114
TI  - Organic materials for printed electronics.
AB  - Organic materials can offer a low-cost alternative for printed electronics and
      flexible displays. However, research in these systems must exploit the
      differences - via molecular-level control of functionality - compared with
      inorganic electronics if they are to become commercially viable.

PMID- 17199112
TI  - An in vitro model of the leukocyte interactions associated with granuloma
      formation in Mycobacterium tuberculosis infection.
AB  - The principal defense of the human host against a Mycobacterium tuberculosis
      infection is the formation of granulomas, organized collections of activated
      macrophages, including epithelioid and multinucleated giant cells, surrounded by
      lymphocytes. This granuloma can sequester and contain the bacteria preventing
      active disease, and if the granuloma is maintained, these bacteria may remain
      latent for a person's lifetime. Secretion of a variety of chemoattractant
      cytokines following phagocytosis of the bacilli by the macrophage is critical not
      only to the formation of the granuloma but also to its maintenance. To
      investigate this process of early granuloma formation, we developed an in vitro
      model composed entirely of human cells. Combining blood lymphocytes and
      autologous macrophages from healthy purified protein derivative skin test
      negative individuals and mycobacteria resulted in the formation of small, rounded
      aggregate structures. Microscopic examination found macrophage-specific CD68(+)
      epithelioid macrophages and small round CD3(+) lymphocytes that in complex
      resembled small granulomas seen in clinical pathology specimens. Acid-fast
      staining bacteria were observed between and possibly within the cells composing
      the granulomas. Supernatants from the infected cells collected at 24 and 48 h and
      5 and 9 days after infection were analyzed by a multiplexed cytokine bead-based
      assay using the Luminex 100 and were found to contain interleukin (IL)-6, IL-8,
      interferon-gamma and tumor necrosis factor-alpha, cytokines known to be involved
      in human granuloma formation, in quantities from two-fold to 7000-fold higher
      than supernatants from uninfected control cells. In addition, chemotaxis assays
      demonstrated that the same supernatants attracted significantly more human
      peripheral blood mononuclear cells than those of uninfected cells (P<0.001). This
      model may provide insight into the earliest stages of granuloma formation in
      those newly infected.

PMID- 17199116
TI  - High-pressure chemistry: benzene bridges under pressure.

PMID- 17199117
TI  - Ferroelectric thin-films: the emancipation of ferroelectricity.

PMID- 17199118
TI  - Nanocomposites: stiffer by design.

PMID- 17199119
TI  - Quasicrystals: when all pieces fit together.

PMID- 17199120
TI  - Material witness: virtuosi's choice.

PMID- 17199121
TI  - Multiferroics: a magnetic twist for ferroelectricity.
AB  - Magnetism and ferroelectricity are essential to many forms of current technology,
      and the quest for multiferroic materials, where these two phenomena are
      intimately coupled, is of great technological and fundamental importance.
      Ferroelectricity and magnetism tend to be mutually exclusive and interact weakly
      with each other when they coexist. The exciting new development is the discovery
      that even a weak magnetoelectric interaction can lead to spectacular cross
      coupling effects when it induces electric polarization in a magnetically ordered
      state. Such magnetic ferroelectricity, showing an unprecedented sensitivity to ap
      plied magnetic fields, occurs in 'frustrated magnets' with competing interactions
      between spins and complex magnetic orders. We summarize key experimental findings
      and the current theoretical understanding of these phenomena, which have great
      potential for tuneable multifunctional devices.

PMID- 17199123
TI  - Opening up peer review.

PMID- 17199122
TI  - Multiferroics: progress and prospects in thin films.
AB  - Multiferroic materials, which show simultaneous ferroelectric and magnetic
      ordering, exhibit unusual physical properties - and in turn promise new device
      applications - as a result of the coupling between their dual order parameters.
      We review recent progress in the growth, characterization and understanding of
      thin-film multiferroics. The availability of high-quality thin-film multiferroics
      makes it easier to tailor their properties through epitaxial strain, atomic-level
      engineering of chemistry and interfacial coupling, and is a prerequisite for
      their incorporation into practical devices. We discuss novel device paradigms
      based on magnetoelectric coupling, and outline the key scientific challenges in
      the field.

PMID- 17199124
TI  - Defining an epigenetic code.
AB  - The nucleosome surface is decorated with an array of enzyme-catalysed
      modifications on histone tails. These modifications have well-defined roles in a
      variety of ongoing chromatin functions, often by acting as receptors for non
      histone proteins, but their longer-term effects are less clear. Here, an attempt
      is made to define how histone modifications operate as part of a predictive and
      heritable epigenetic code that specifies patterns of gene expression through
      differentiation and development.

PMID- 17199125
TI  - Lipid rafts: at a crossroad between cell biology and physics.
AB  - Membrane lateral heterogeneity is accepted as a requirement for the function of
      biological membranes and the notion of lipid rafts gives specificity to this
      broad concept. However, the lipid raft field is now at a technical impasse
      because the physical tools to study biological membranes as a liquid that is
      ordered in space and time are still being developed. This has lead to a
      disconnection between the concept of lipid rafts as derived from biochemical and
      biophysical assays and their existence in the cell. Here, we compare the concept
      of lipid rafts as it has emerged from the study of synthetic membranes with the
      reality of lateral heterogeneity in biological membranes. Further application of
      existing tools and the development of new tools are needed to understand the
      dynamic heterogeneity of biological membranes.

PMID- 17199126
TI  - Leading-edge research: PtdIns(3,4,5)P3 and directed migration.

PMID- 17199127
TI  - Sculpting a fly leg: BMP boundaries and cell death.

PMID- 17199129
TI  - Wapl takes cohesin off chromosome arms.

PMID- 17199128
TI  - Heterochromatin: condense or excise.

PMID- 17199130
TI  - Telomeres on the Cdk roller-coaster ride.

PMID- 17199131
TI  - Physiogenomic comparison of weight profiles of olanzapine- and risperidone
      treated patients.
AB  - Atypical antipsychotics induce pre-diabetic symptoms in some but not all
      patients, characterized most notably by elevated weight. The side effect profiles
      of the various drugs in the class differ, however, raising the possibility of
      drug-specific mechanisms for similar side effects. We used physiogenomic
      analysis, an approach previously employed to study the genetics of drug and diet
      response, to discover and compare genetic associations with weight profiles
      observed in patients treated with olanzapine and risperidone as an approach to
      unraveling contrasting mechanistic features of both drugs. A total of 29 single
      nucleotide polymorphisms (SNPs) were selected from 13 candidate genes relevant to
      two potential pharmacological axes of psychotropic-related weight profiles,
      appetite peptides and peripheral lipid homeostasis. We applied physiogenomic
      analysis to a cross-section of 67 and 101 patients being treated with olanzapine
      and risperidone, respectively, and assessed genetic associations with the weight
      profiles. Weight profiles in patients treated with olanzapine were significantly
      associated with SNPs in the genes for apolipoprotein E, apolipoprotein A4 and
      scavenger receptor class B, member 1. Weight profiles in patients treated with
      risperidone were significantly associated with SNPs in the genes for leptin
      receptor, neuropeptide Y receptor Y5 and paraoxonase 1. These results are
      consistent with contrasting mechanisms for the weight profile of patients treated
      with these drugs. Genes associated with olanzapine weight profiles may be related
      to peripheral lipid homeostatic axes, whereas those associated with risperidone's
      may be related to brain appetite peptide regulation. Future physiogenomic studies
      will include neurotransmitter receptor SNPs and validation in independent
      samples.

PMID- 17199132
TI  - beta2-Adrenergic receptor gene variants and risk for autism in the AGRE cohort.
AB  - The beta2-adrenergic receptor is part of the catecholamine system, and variants
      at two polymorphic sites in the gene coding for the receptor (ADRB2) confer
      increased activity. Overstimulation of this receptor may alter brain development,
      and has been linked to autism in non-identical twins. The objective of this study
      was to determine whether alleles in ADRB2 are associated with diagnosis of autism
      in the Autism Genetic Resource Exchange (AGRE) population. Three hundred and
      thirty-one independent autism case-parent trios were included in the analysis.
      Subjects were genotyped at activity-related polymorphisms rs1042713 (codon 16)
      and rs1042714 (codon 27). Association between autism and genotypes at each
      polymorphic site was tested using genotype-based transmission disequilibrium
      tests, and effect modification by family and pregnancy characteristics was
      evaluated. Sensitivity to designation of the proband in each family was assessed
      by performing 1000 repeats of the analysis selecting affected children randomly.
      A statistically significant OR of 1.66 for the Glu27 homozygous genotype was
      observed. Increased associations with this genotype were observed among a subset
      of Autism Diagnostic Observation Schedule confirmed cases and a subset reporting
      experience of pregnancy-related stressors. In conclusion, the Glu27 allele of the
      ADRB2 gene may confer increased risk of autism and shows increased strength with
      exposure to pregnancy related stress.

PMID- 17199133
TI  - Serum prostate-specific antigen as a predictor of prostate volume in Korean men
      with lower urinary tract symptoms.
AB  - The aim of the study was to assess the utility of prostate-specific antigen (PSA)
      as a predictor of prostate volume indexes (total prostate volume (TPV),
      transition zone volume and transition zone index) in Korean men with lower
      urinary tract symptoms (LUTS). From September 2003 to April 2006, 3431 patients
      with LUTS were included in the study; they had a median age of 63.8 years, a
      median prostate volume of 22.6 ml and a median serum PSA of 1.04 ng/ml. Men with
      a baseline PSA of >10 ng/ml were excluded, to reduce the likelihood of including
      occult prostate cancer. Prostate volume indexes and serum PSA levels had an age
      dependent log-linear relationship. Receiver operating characteristic curve
      analysis showed that PSA had good predictive value for various prostate volume
      indexes thresholds. The approximate age-specific criteria for detecting men with
      a TPV of >40 ml are PSA levels of 1.20, 1.44 and 1.72 ng/ml for men with LUTS in
      their sixth, seventh and eighth decades, respectively. The results show that
      serum PSA identifies Korean men with large prostates reasonably well. Korean men
      may produce and/or release more PSA per unit prostate volume than white men. The
      cutoffs for PSA and prostate volume to response to LUTS therapy should be
      determined in this population.

PMID- 17199134
TI  - Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist
      (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a
      phase III randomized, double-blind, multicenter trial in Japanese patients.
AB  - To compare combination therapy with bicalutamide 80 mg and a luteinizing hormone
      releasing hormone agonist (LHRH-A) versus LHRH-A alone in Japanese men with
      untreated advanced prostate cancer. A total of 205 patients with stage C/D
      prostate cancer were randomized to either LHRH-A+once-daily oral bicalutamide 80
      mg or placebo. Primary study variables have been reported previously. Secondary
      variables included: time to achieve prostate-specific antigen < or = 4 ng/ml,
      time-to-treatment failure (TTTF), time-to-disease progression (TTP), overall
      survival (OS), adverse events and adverse drug reactions. Following combination
      therapy with bicalutamide 80 mg, there were significant (P<0.001) advantages over
      LHRH-A alone in terms of TTTF and TTP, but the difference in the interim OS was
      not statistically significant. First-line combination therapy with bicalutamide
      80 mg in Japanese patients with advanced prostate cancer offers significant
      benefits over LHRH-A alone, with respect to TTTF and TTP. Follow-up for OS
      continues.

PMID- 17199135
TI  - Global analysis of differentially expressed genes in androgen-independent
      prostate cancer.
AB  - Progression to androgen independent (AI) is the main cause of death in prostate
      cancer, and the mechanism is still unclear. By reviewing the expression profiles
      of 26 prostate cancer samples in a holistic view, we found a group of genes
      differentially expressed in AI compared with androgen-dependent groups (P
      value<0.01, t-test). Focusing on apoptosis, proliferation, hormone and
      angiogenesis, we found a group of genes such as thioredoxin domain containing 5 ,
      tumor necrosis factor receptor superfamily, member 10a , ribosomal protein S19
      and Janus kinase 2 upregulated in AI prostate cancer, could play important roles
      in the transition from AD to AI and could be biomarkers of prognosis.

PMID- 17199136
TI  - Experimental rodent models of prostatitis: limitations and potential.
AB  - Prostatitis is a polyetiological inflammation of the prostate gland in men
      characterized by pelvic pain, irritative voiding symptoms, and sexual
      dysfunction. Histologically prostatitis is characterized by poly- and mononuclear
      cell infiltrates (neutrophils, lymphocytes, macrophages and plasma cells) in the
      stromal connective tissue around the acini or ducts. Prostatitis is an important
      worldwide health problem in men. The pathogenesis and diagnostic criteria for the
      condition are obscure, with the result that the development of management
      programs for this condition has been hindered. Animal model(s) might be useful in
      elucidating mechanisms involved in the molecular pathogenesis of chronic
      nonbacterial prostatitis and chronic pelvic pain syndrome. Given that prostatitis
      might have a multifactorial etiology, several animal models with unique features
      may prove helpful. This review examines a number of experimental rodent models of
      prostatitis and evaluates their advantages and limitations.

PMID- 17199137
TI  - Reflection on the 2005 Budapest Meeting of the European Ethics Consortium.

PMID- 17199138
TI  - A new model for science communication that takes ethical considerations into
      account: the three-E model: entertainment, emotion and education.

PMID- 17199140
TI  - From stratospheric ozone to climate change: historical perspective on precaution
      and scientific responsibility.
AB  - The issue of the impact of human activities on the stratospheric ozone layer
      emerged in the early 1970s. But international regulations to mitigate the most
      serious effects were not adopted until the mid-1980s. This case holds lessons for
      addressing more complex environmental problems. Concepts that should inform
      discussion include 'latency,' 'counter-factual scenario based on the
      Precautionary Principle,' 'inter-generational burden sharing,' and 'estimating
      global costs under factual and counter-factual regulatory scenarios.' Stringent
      regulations were adopted when large scientific uncertainty existed, and the
      environmental problem would have been prevented or more rapidly mitigated, at
      relatively modest incremental price, but for a time delay before more rigorous
      Precautionary measures were implemented. Will history repeat itself in the case
      of climate change?

PMID- 17199141
TI  - Climate change: do we know enough for policy action?
AB  - The climate change problem must be thought of in terms of risk, not certainty.
      There are many well-established elements of the problem that carry considerable
      confidence whereas some aspects are speculative. Therefore, the climate problem
      emerges not simply as a normal science research issue, but as a risk management
      policy debate as well. Descriptive science entails using empirical and
      theoretical methods to quantify the two factors that go into risk assessment:
      "What can happen?" and "What are the odds?" (Probability x Consequences).
      Policymakers should, in turn, take that information and use it to make value
      judgments about what is safe, what is dangerous, what is fair. To make these
      judgments, policymakers need to know the probabilities that experts assign to
      various possible outcomes in order to make risk management decisions to hedge
      against unsafe, dangerous and unfair outcomes. The climate debate needs to be
      reframed away from absolute costs--or benefits--into relative delay times to
      achieve specific caps or to avoid crossing specific agreed 'dangerous' climate
      change thresholds. Even in most optimistic scenarios, CO2 will stabilize at a
      much higher concentration than it has reached today, and temperature will rise
      accordingly. It will take even longer for sea level rise from thermal expansion
      and the melting of polar ice to occur, but what is most problematic is that how
      we handle our emissions now and in the next five decades preconditions the
      sustainability of the next millennium.

PMID- 17199143
TI  - A network approach for distinguishing ethical issues in research and development.
AB  - In this paper we report on our experiences with using network analysis to discern
      and analyse ethical issues in research into, and the development of, a new
      wastewater treatment technology. Using network analysis, we preliminarily
      interpreted some of our observations in a Group Decision Room (GDR) session where
      we invited important stakeholders to think about the risks of this new
      technology. We show how a network approach is useful for understanding the
      observations, and suggests some relevant ethical issues. We argue that a network
      approach is also useful for ethical analysis of issues in other fields of
      research and development. The abandoning of the overarching rationality
      assumption, which is central to network approaches, does not have to lead to
      ethical relativism.

PMID- 17199142
TI  - An ethics of expertise based on informed consent.
AB  - Ethicists widely accept the notion that scientists have moral responsibilities to
      benefit society at large. The dissemination of scientific information to the
      public and its political representatives is central to many of the ways in which
      scientists serve society. Unfortunately, the task of providing information can
      often give rise to moral quandaries when scientific experts participate in
      politically charged debates over issues that are fraught with uncertainty. This
      paper develops a theoretical framework for an "ethics of expertise" (EOE) based
      on the notion that scientists have responsibilities to provide information in a
      way that promotes autonomous decision-making on the part of the public and its
      representatives. Moreover, insofar as the principle of informed consent has
      developed in biomedical ethics as a way for physicians to promote autonomous
      decision-making on the part of their patients, this paper suggests that the
      informed-consent concept may suggest a set of criteria and guidelines that can
      help scientists to fulfill their similar ethical responsibilities to the public.
      In order to illustrate how the resulting EOE could provide practical guidance for
      scientific experts, the paper examines a case study involving the dissemination
      of information about the low-dose biological effects of toxic chemicals and
      carcinogens.

PMID- 17199144
TI  - Applying the rules of just war theory to engineers in the arms industry.
AB  - Given the close relationship between the modern arms industry and the military,
      engineers and other professionals who work in the arms industry should be held
      accountable to the principles of just war theory. While they do not deploy
      weapons on the battlefield and are not in the military chain of command,
      technical professionals nonetheless have a moral duty to abide by principles of
      jus ad bellum and jus in bello. They are morally responsible both for choosing
      the companies that employ them (and to whom these companies sell arms) and a well
      as what types of arms they develop.

PMID- 17199145
TI  - Integrating ethics in design through the value-sensitive design approach.
AB  - The Accreditation Board of Engineering and Technology (ABET) has declared that to
      achieve accredited status, 'engineering programs must demonstrate that their
      graduates have an understanding of professional and ethical responsibility.' Many
      engineering professors struggle to integrate this required ethics instruction in
      technical classes and projects because of the lack of a formalized ethics-in
      design approach. However, one methodology developed in human-computer interaction
      research, the Value-Sensitive Design approach, can serve as an engineering
      education tool which bridges the gap between design and ethics for many
      engineering disciplines. The three major components of Value-Sensitive Design,
      conceptual, technical, and empirical, exemplified through a case study which
      focuses on the development of a command and control supervisory interface for a
      military cruise missile.

PMID- 17199146
TI  - Integrating ethics into technical courses: micro-insertion.
AB  - Perhaps the most common reason science and engineering faculty give for not
      including 'ethics' (that is, research ethics, engineering ethics, or some
      discussion of professional responsibility) in their technical classes is that
      'there is no room'. This article 1) describes a technique ('micro-insertion')
      that introduces ethics (and related topics) into technical courses in small
      enough units not to push out technical material, 2) explains where this technique
      might fit into the larger undertaking of integrating ethics into the technical
      (scientific or engineering) curriculum, and 3) concludes with some quantified
      evidence (collected over more than a decade) suggesting success. Integrating
      ethics into science and engineering courses is largely a matter of providing
      context for what is already being taught, context that also makes the material
      already being taught seem 'more relevant'.

PMID- 17199148
TI  - Understanding the kinetics of spin-forbidden chemical reactions.
AB  - Many chemical reactions involve a change in spin-state and are formally
      forbidden. This article summarises a number of previously published applications
      showing that a form of Transition State Theory (TST) can account for the kinetics
      of these reactions. New calculations for the emblematic spin-forbidden reaction
      HC + N(2) are also reported. The observed reactivity is determined by two
      factors. The first is the critical energy required for reaction to occur, which
      in spin-forbidden reactions is often defined by the relative energy of the
      Minimum Energy Crossing Point (MECP) between potential energy surfaces
      corresponding to the different spin states. The second factor is the probability
      of hopping from one surface to the other in the vicinity of the crossing region,
      which is largely defined by the spin-orbit coupling matrix element between the
      two electronic wavefunctions. The spin-forbidden transition state theory takes
      both factors into account and gives good results. The shortcomings of the theory,
      which are largely analogous to those of standard TST, are discussed. Finally, it
      is shown that in cases where the surface-hopping probability is low, the kinetics
      of spin-forbidden reactions will be characterised by unusually unfavourable
      entropies of activation. As a consequence, reactions involving a spin-state
      change can be expected to compete poorly with spin-allowed reactions at high
      temperatures (or energies).

PMID- 17199147
TI  - The Budapest Meeting 2005 intensified networking on ethics of science: the case
      of reproductive cloning, germline gene therapy and human dignity.
AB  - This paper reports on the meeting of the Sounding Board of the EU Reprogenetics
      Project that was held in Budapest, Hungary, 6-9 November 2005. The Reprogenetics
      Project runs from 2004 until 2007 and has a brief to study the ethical aspects of
      human reproductive cloning and germline gene therapy. Discussions during The
      Budapest Meeting are reported in depth in this paper as well as the initiatives
      to involve the participating groups and others in ongoing collaborations with the
      goal of forming an integrated network of European resources in the fields of
      ethics of science.

PMID- 17199149
TI  - Non-linear plasmon response to protein binding at a nanostructured gold particle
      plasmon resonance surface.
AB  - Rapid adsorption kinetics have been observed for protein binding to a 800 nm
      aggregated nanoparticle, showing extreme sensitivity resulting from a non-linear
      particle plasmon response.

PMID- 17199150
TI  - A scanning force microscopy study on the motion of single brush-like
      macromolecules on a silicon substrate induced by coadsorption of small molecules.
AB  - Scanning force microscopy was applied to visualise the motion of single
      poly(butanoate-ethylmethacrylate)-graft-poly(n-butyl acrylate) molecules on
      silicon and SrTiO(3) substrates. Macromolecular mobility was induced by cyclic
      exposure of the wafers with the adsorbed brush-like macromolecules to water and
      alcohol vapours. Exposure to saturated alcohol vapour induced collapse of the
      adsorbed individual polymer chains while exposure to saturated water vapour
      promoted their extension. The characteristic times of both conformational changes
      were long enough that it was possible to visualise step-by-step the morphology
      transformation in situ by means of an environment-controlled scanning force
      microscope. Several successive collapse-decollapse cycles were recorded, and
      small diffusive shifts of the macromolecular position on the substrate were
      detected after each cycle. Manipulating and visualising single polymer molecules
      in situ and real time on a silicon substrate opens up new possibilities for the
      controlled structure formation in ultrathin polymer films. As shown on the sample
      of a faceted SrTiO(3) wafer, upon extension the brush-like molecules can crawl or
      extend along nanoscopic surface structures. Silicon can be structured both
      topographically and chemically at dimensions comparable to those of single
      polymer molecules with a variety of fabrication techniques ranging from well
      established conventional silicon micro- nano- machining to new tools constantly
      developed as dip-pen and nanoimprint lithography.

PMID- 17199151
TI  - Laser-muon spin spectroscopy in liquids - a technique to study the excited state
      chemistry of transients.
AB  - This study introduces laser-muon spin spectroscopy in the liquid phase, which
      extends muonium chemistry in liquids to the realm of excited states and enables
      the detection of muoniated molecules by their spin evolution after laser
      excitation. This leads to new opportunities to study the Kinetic Isotope Effects
      (KIEs) of muonium/atomic hydrogen reactions and to probe transient chemistry in
      radiolysis processes involved in muonium formation, as well as muoniated
      intermediates in excited states.

PMID- 17199152
TI  - NMR crystallography of oxybuprocaine hydrochloride, Modification II degrees.
AB  - The (13)C CPMAS spectrum is presented for the polymorph of oxybuprocaine
      hydrochloride which is stable at room temperature, i.e. Mod. II degrees . It
      shows crystallographic splittings arising from the fact that there are two
      molecules, with substantially different conformations, in the asymmetric unit. An
      INADEQUATE two-dimensional experiment was used to link signals for the same
      independent molecule. The chemical shifts are discussed in relation to the
      crystal structure. Of the four ethyl groups attached to NH(+) nitrogens, one
      gives rise to unusually low chemical shifts, very different from those of the
      other three ethyl groups. This is attributed empirically to gamma-gauche
      conformational effects, as is confirmed by shielding computations. These
      considerations allow (13)C signals to be assigned to specific carbons in the two
      crystallographically inequivalent molecules in the crystal structure. Indeed,
      information about the conformations is inherent in the NMR spectrum, which thus
      provides data of crystallographic significance. A (13)C/(1)H HETCOR experiment
      enabled resolution to be obtained in the (1)H dimension and allowed (1)H and
      (13)C signals for the same independent molecule to be linked.

PMID- 17199153
TI  - Chirp-driven vibrational distribution in transition metal carbonyl complexes.
AB  - In this theoretical study vibrational ladder climbing in transition metal
      carbonyl complexes, as a possible means to initialize chemical ground state
      reactions, and the resulting vibrational population distribution using chirped
      mid-infrared femtosecond laser pulses is investigated. Our model system is
      MnBr(CO)(5), a strong IR-absorber within an experimentally easily accessible
      wavelength region. Special emphasis is put on the perturbation due to additional
      vibrational modes, especially on one, which allows dissociation at low energies.
      The related potential energy surface for the three representative modes is
      calculated, whereon quantum dynamics calculations, including the laser-molecule
      interaction, are performed. No significant coupling could be detected, neither in
      the bound, nor in the dissociative region. Contrarily, we found a dynamical
      barrier even for energies high above the dissociation limit. Different
      vibrational population distributions after the laser excitation of the CO
      stretching mode could be generated in dependence of the chirp parameters. Based
      on these findings we simulated the laser excitation corresponding to an
      experiment by M. Joffre et al., Proc. Natl. Acad. Ssi. U. S. A., 2004, 101(36),
      13216-13220, where coherent vibrational ladder climbing in carboxyhemoglobin was
      demonstrated and we could offer an explanation for an open question, concerning
      the interpretation of the spectroscopic data.

PMID- 17199154
TI  - Identification of hydrolysis products of AlCl(3)*6H(2)O in the presence of
      sulfate by electrospray ionization time-of-flight mass spectrometry and
      computational methods.
AB  - ElectroSpray Ionization-Mass Spectrometry (ESI-MS) and computational methods
      (DFT, MP2, and COSMO) were used to investigate the hydrolysis products of
      aluminium chloride as a function of sulfate concentration at pH 3.7. With the aid
      of computational chemistry, structural information was deduced from the chemical
      compositions observed with ESI-MS. Many novel types of hydrolysis products were
      noted, revealing that our present understanding of aluminium speciation is too
      simple. The role of counterions was found to be critical: the speciation of
      aluminium changed markedly as a function of sulfate concentration. Ab initio
      calculations were used to reveal the energetically most favoured structures of
      aluminium sulfate anions and cations selected from the ESI-MS results. Several
      interesting observations were made. Most importantly, the bonding behaviour of
      the sulfate group changed as the number of aqua ligands increased. The
      accompanying structural rearrangement of the clusters revealed the highly active
      role of sulfate as a ligand. The gas phase calculations were expanded to the
      aquatic environment using a conductor-like screening model. As expected, the
      bonding behaviour of the sulfate group in the minimum energy structures was
      distinctly different in the aquatic environment compared to the gas phase.
      Together, these methods open a new window for research in the solution chemistry
      of aluminium species.

PMID- 17199155
TI  - Fluorescence emission from photo-fragments after resonant S 2p excitations in
      H2S.
AB  - Visible-UV fluorescence emission of gas-phase hydrogen sulfide, H(2)S, has been
      studied at the S 2p edge with synchrotron radiation excitation. Dispersed
      fluorescence measurements in the wavelength range 300-900 nm were taken at
      several photon energies corresponding to the excitations of the S 2p electrons to
      the unoccupied molecular and Rydberg orbitals. The spectra reveal fluorescence
      from the H, S, S(+), HS and HS(+) photo-fragments. H is found to be the strongest
      emitter at Rydberg excitations, while the emission from S(+) is dominant at the
      molecular resonances and above the S 2p ionization thresholds. The intensities of
      hydrogen Lyman-alpha (122 nm), Balmer-alpha (656 nm), Balmer-beta (486 nm)
      transitions as well as the visible-UV total fluorescence yield (300-900 nm) and
      the total ion yield were measured by scanning the photon energy in small steps
      across the S 2p edge. The different Balmer lines show some sensitivity to the
      specific core excitations, which is, however, not so strong as that recently
      observed in the water molecule [E. Melero Garcia, A. Kivimaki, L. G. M.
      Pettersson, J. Alvarez Ruiz, M. Coreno, M. de Simone, R. Richter and K. C.
      Prince, Phys. Rev. Lett., 2006, 96, 063003].

PMID- 17199156
TI  - A diffusional alternative to the Marcus free energy gap law.
AB  - The results of the precise kinetic fitting of the highly exergonic electron
      transfer from excited perylene to tetracyanoethylene in acetonitrile were used to
      estimate the Stern-Volmer constant of perylene quenching by double channel
      electron transfer (to the ground and excited states of the radical ion pair). It
      appears that the Stern-Volmer constant is exactly the same as the diffusional
      height of the Rehm-Weller plateau, substituting the exergonic wing of the Marcus
      free energy gap law. Even the single channel transfer is shown to be fast enough
      that the quenching should be under true diffusional control at the highest
      available exergonicity.

PMID- 17199157
TI  - A high-resolution infrared spectroscopic investigation of the halogen atom-HCN
      entrance channel complexes solvated in superfluid helium droplets.
AB  - Rotationally resolved infrared spectra are reported for the X-HCN (X = Cl, Br, I)
      binary complexes solvated in helium nanodroplets. These results are directly
      compared with those obtained previously for the corresponding X-HF complexes [J.
      M. Merritt, J. Kupper and R. E. Miller, Phys. Chem. Chem. Phys., 2005, 7, 67].
      For bromine and iodine atoms complexed with HCN, two linear structures are
      observed and assigned to the (2)Sigma(1/2) and (2)Pi(3/2) ground electronic
      states of the nitrogen and hydrogen bound geometries, respectively. Experiments
      for HCN + chlorine atoms give rise to only a single band which is attributed to
      the nitrogen bound isomer. That the hydrogen bound isomer is not stabilized is
      rationalized in terms of a lowering of the isomerization barrier by spin-orbit
      coupling. Theoretical calculations with and without spin-orbit coupling have also
      been performed and are compared with our experimental results. The possibility of
      stabilizing high-energy structures containing multiple radicals is discussed,
      motivated by preliminary spectroscopic evidence for the di-radical Br-HCCCN-Br
      complex. Spectra for the corresponding molecular halogen HCN-X(2) complexes are
      also presented.

PMID- 17199158
TI  - A computational study on N2 adsorption in Cu-ZSM-5.
AB  - The present computational study investigates the adsorption of N(2) by Cu-ZSM-5,
      with particular regard to the interaction with pairs of Cu(+) ions, employing
      simple cluster models in the calculations. It shows that several interaction
      patterns between N(2) and couples of Cu(+) sites are possible within the Cu-ZSM-5
      structure. In particular, when pairs of Cu(+) ions are located at opposite sides
      of ten-membered rings, in the region where linear and sinusoidal channels
      intersect each other, a quasi-linear Cu-N-N-Cu adsorption occurs. Although
      lattice restraints cause small deviations from linearity, such interaction turned
      out to be more favourable than other adsorption patterns within the Cu-ZSM-5
      structure. The linearity of the Cu-N-N-Cu fragment and the relatively low
      concentration of the related sites cause a low extinction coefficient for the N-N
      IR stretching mode, which is usually detected with very low intensity or not
      detected at all. The results of the present calculations may explain the
      experimental evidence for a nearly IR-silent fraction of nitrogen strongly
      adsorbed in the Cu-ZSM-5 catalyst which, as shown in a previous work, is linearly
      related to the number of active sites for NO decomposition.

PMID- 17199159
TI  - [New drugs in the treatment of noninfectious uveitis].

PMID- 17199160
TI  - Intravitreal Bioerudivel sustained-release triamcinolone microspheres system
      (RETAAC). Preliminary report of its potential usefulnes for the treatment of
      diabetic macular edema.

PMID- 17199161
TI  - [Mitomycin C versus 5-FU in failing blebs needling].

PMID- 17199162
TI  - [Submacular hemorrhage following photodynamic therapy in the treatment of
      choroidal neovascularization].
AB  - PURPOSE: To describe the incidence, clinical features and evolution of submacular
      hemorrhage (SMH) occurring after photodynamic therapy (PDT) with verteporfin in
      the treatment of choroidal neovascularization (CNV). METHODS: A retrospective
      analysis of the patients treated with PDT in our hospital between July 2002 and
      May 2005 was undertaken. RESULTS: 8 out of 504 eyes treated with PDT (1.58%)
      developed SMH; 4 of them (0.79%) required surgical attack. The incidence of SMH
      for every application of PDT was 0.65% (8/1221). The underlying disorder defined
      was age-related macular degeneration (AMD) in 7 cases (87.5%), and high myopia in
      one case (12.5%). Regarding the type of lesion, 5 were occult (62.5%; p=0.01), 1
      predominantly classic, 1 minimally classic, and the last one was not classified.
      The average final visual acuity (VA) was 0.057, with 25% of patients having a VA
      >or= 0.1. Patients lost 4 Snellen lines on average. CONCLUSIONS: SMH after PDT
      was an event of unknown etiology and low frequency. The incidence in our series
      (1.58%) was comparable with that described in the world literature (0.24-9.0%).
      The greatest incidence of AMD was in the occult group with no classic type of
      CNV, suggesting a possible higher risk for SMH in this type of lesion. It is
      mandatory to inform patients of the possibility of this complication, which can
      compromise the visual result of the PDT, and sometimes require surgery. The low
      risk of SMH related to the PDT justifies its application when it is indicated.

PMID- 17199163
TI  - [Diagnostic usefulness of optical coherence tomography (OCT), scanning laser
      tomography (HRT-II) and laser polarimetry (GDx) in open-angle glaucoma].
AB  - PURPOSE: To evaluate the diagnostic ability of three digital imaging technologies
      (HRT-II, OCT and GDx VCC) in detecting glaucomatous damage. METHODS: A total of
      427 eyes from 427 subjects were included in this cross-sectional study. Each
      subject was classified as healthy, ocular hypertensive or glaucomatous, according
      to intraocular pressure levels, standard automated perimetry and optic disc
      morphology. All of them underwent examination by means of HRT, OCT and GDx VCC.
      Receiver operating characteristic (ROC) curves were plotted and sensitivities at
      fixed specificities (85% and 95%) were calculated for each parameter assessed.
      RESULTS: The parameters with the higher diagnostic ability were: FSM discriminant
      function from HRT-II (AUC=0.899), retinal nerve fiber layer average thickness
      from OCT (AUC=0.929) and NFI from GDx VCC (AUC=0.879), with no statistically
      significant differences between them. CONCLUSION: The HRT-II, OCT and GDx VCC
      provide measurements of the retinal nerve fiber layer and the optic nerve head
      with high discriminating ability in open-angle glaucoma.

PMID- 17199164
TI  - [Results of an outpatient major surgery program in ophthalmology].
AB  - PURPOSE: To evaluate the outcomes in our hospital of an ambulatory major surgery
      program in patients with a variety of different ocular pathologies. METHOD: This
      retrospective study includes 13,878 patients who underwent programmed surgery by
      the Department of Ophthalmology between September 1998 and December 2004.
      Different ophthalmological surgical procedures were performed as outpatient
      surgery in 11,187 patients, with cataract surgery (phacoemulsification) being the
      most frequent operation performed (8,155 cases). We have analysed several
      indicators (substitution, suspension, admission and readmission rates), as well
      as surgical yield and systemic and ocular complications which appeared within 72
      hours after surgery. The variables were measured as relative frequencies. The
      evolution of complications during the study period was analysed by the Chi-square
      trend test. RESULTS: 13,878 patients had ophthalmic surgery during the study
      period; 11,187 had outpatient surgery with a global substitution ratio of 80.6%.
      The median surgical yield was 74.36%. The admission rate after surgery was 4.46%
      (499 patients), with 92.18% (460) of these requiring immediate admission. Twenty
      one patients suffered from severe complications (cardiovascular, neurological,
      metabolic, infectious), representing a proportional risk of 1:532. Forty-five
      patients had less severe complications (arterial hypertension, nausea, vomiting,
      vasovagal syncope) that required admission to hospital. Ophthalmologic
      complications occurred in 79 cases (0.56%). CONCLUSIONS: Ambulatory major surgery
      (AMS) is an excellent organization model of multidisciplinary surgical assistance
      that makes it possible to treat well selected patients in an effective, safe and
      efficient manner. There is a low incidence of postoperative complications of
      variable severity despite following the optimum requisites, although fortunately
      mortality is practically absent.

PMID- 17199165
TI  - [Ocular findings in Carney complex].
AB  - CASE REPORT: Carney complex (CNC) is a multiple neoplasia syndrome, inherited in
      an autosomal dominant manner, characterized by myxomas, spotty skin pigmentation,
      endocrine tumors and ophthalmic abnormalities. DISCUSSION: We report the ocular
      findings which usually precede the most serious component of the complex, the
      cardiac myxoma.

PMID- 17199166
TI  - [Atypical macular coloboma: a case report].
AB  - CLINICAL CASE: This was a 15-month-old boy who had macular retinochoroidal
      lesions in both eyes following maternal varicella during pregnancy. DISCUSSION:
      The scars were suggestive of congenital chorioretinal infection, but because of
      negative serology and the clinical picture, we believe the problems are atypical
      macular colobomata.

PMID- 17199167
TI  - [Serous macular detachment as an atypical sign in cat scratch disease].
AB  - CASE REPORT: A 58-year-old woman presented with 0.1 visual acuity in the left eye
      associated with a serous retinal detachment of the macula as the only ocular
      manifestation of cat scratch disease. This diagnosis was made by serum antibody
      titers and the clinical course. DISCUSSION: Although uncommon, cat scratch
      disease should be considered in patients with a serous detachment in the macula
      region of the retina.

PMID- 17199168
TI  - [Malignant exophtalmos in hyperthyroidism with a hypothyroid crisis].
AB  - CASE REPORT: We present the case of a 56-year-old male with a malignant
      exophthalmos in the context of Graves' disease. He suffered a significant
      worsening coincident with a hypothyroid crisis, and various therapeutic
      approaches were required for reduction of the proptosis. DISCUSSION: When
      managing this condition, both the severity of the exophthalmos and the activity
      of the thyroid must be considered when choosing which of the different
      therapeutic approaches should be employed.

PMID- 17199169
TI  - [Goethe and colors].

PMID- 17199170
TI  - [To Benjamin Franklin, father of bifocal lenses, on the 300th anniversary of his
      birth].

PMID- 17199171
TI  - [Prevalence of the metabolic syndrome in ischaemic stroke population].
AB  - BACKGROUND AND PURPOSE: The metabolic syndrome (MetSyn), especially diabetes or
      dyslipidaemias, predisposes to cardiovascular disease or stroke development. We
      aimed to evaluate the prevalence of MetSyn in a non-selected population of acute
      ischaemic stroke (IS) patients using three definitions. METHODS: We analyzed 763
      IS patients (426 women, 337 men) consecutively admitted to a tertiary referral
      hospital specializing in acute stroke care (1.01.2003-30.09.2005). MetSyn was
      diagnosed in the presence of three from five disturbances (alimentary or simple
      obesity, increased blood pressure, increased triglycerides, low HDL cholesterol,
      fasting hyperglycaemia) according to definitions of: National Cholesterol
      Education Program Adult Treatment Panel III (NCEP-ATP III), International
      Diabetes Federation (IDF), American Heart Association - National Heart, Lung and
      Blood Institute (AHA-NHLBI). RESULTS: MetSyn was diagnosed according to criteria
      NCEP-ATP III, IDF, AHA-NHLBI in 54.3, 60.8 and 63.5% of IS patients,
      respectively, with significantly higher prevalence in women than in men in all
      age groups. Hypertension was the most frequent disturbance (93.7%). Alimentary or
      simple obesity and low HDL cholesterol level were significantly more frequent in
      women than in men (visceral obesity: NCEP-ATP III - 60.7 vs. 26.6%, IDF - 82 vs.
      55.8%, AHA-NHLBI - 63.1 vs. 28.2%, respectively; low HDL cholesterol: 56.8 vs.
      42%). CONCLUSIONS: Over half of acute ischaemic stroke patients have MetSyn, but
      in the female population MetSyn is 1.5 times more frequent than in men. It is
      necessary to pay a special attention to the population with MetSyn because of the
      high risk of ischaemic stroke.

PMID- 17199172
TI  - [Evaluation of needs in early post-stroke rehabilitation in Poland].
AB  - BACKGROUND AND PURPOSE: According to European Stroke Initiative (EUSI)
      recommendations every stroke patient should undergo rehabilitation. We aimed to
      evaluate the needs of comprehensive stroke in-patient rehabilitation in Poland.
      MATERIALS AND METHODS: We designed and distributed a questionnaire evaluating
      rehabilitation departments in Poland, where stroke patients undergo early
      rehabilitation. Comprehensive rehabilitation was defined as: kinesitherapy
      (minimum 60 minutes/day), speech therapy (minimum 30 minutes 5 days a week),
      rehabilitation of other cognitive impairments and group kinesitherapy. We
      separated rehabilitation departments where comprehensive post-stroke
      rehabilitation is conducted, and calculated the number of beds in these
      departments only for stroke patients. We estimated the number of acute stroke
      patients in Poland. We evaluated the number of patients requiring in-patient
      rehabilitation based on results from the 2nd Department of Neurology, Institute
      of Psychiatry and Neurology, Warsaw, where all stroke patients who need in
      patient rehabilitation have such a possibility. We estimated the number of beds
      required in rehabilitation departments for stroke patients in Poland. RESULTS: We
      obtained responses from 115 out of 172 (66.9%) rehabilitation departments.
      Comprehensive post-stroke rehabilitation is conducted in 11 departments. 159 beds
      in these departments are for stroke patients. From 64,896 acute stroke patients
      9,927 will need in-patient rehabilitation. We need 604 more beds in
      rehabilitation departments for stroke patients in Poland. CONCLUSION: Only 10% of
      rehabilitation departments could provide comprehensive stroke rehabilitation in
      Poland. At present, the number of beds in rehabilitation departments for stroke
      patients covers about 20.8% of actual needs. An increased number of
      rehabilitation beds for stroke patients could result in a decreased number of
      disabled post-stroke patients.

PMID- 17199173
TI  - [Long-term result of the surgical treatment of craniopharyngiomas].
AB  - BACKGROUND AND PURPOSE: The aim of the study was to assess the long-term outcome
      in patients with cranipharyngioma, depending on the extent of tumour removal.
      MATERIAL AND METHODS: Thirty-six patients (17 females and 19 males), aged between
      10 and 57, were treated at the Clinic of Neurosurgery of the Medical University
      of Warsaw between 1990 and 2004. The most common initial symptoms included:
      decreased visual acuity in 75% of cases, visual field defect in 69% of cases,
      headaches in 58% cases and endocrine disorders in 50% of cases. The initial
      diagnosis was based on two-phase computed tomography (CT) and magnetic resonance
      imaging (MRI). The most common means of surgical access was by pterional
      craniotomy, which was used in 27 cases. Due to tumour localisation, other
      accesses (bifrontal - basal, transventricular and transsphenoidal) were also
      used. RESULTS: The tumour removal was considered total in 31%, subtotal in 38%,
      and partial in 31%. In the post-operational period 2 patients died. Control
      examinations were performed to investigate long-term outcome: two-phase MRI or
      CT, evaluations of visual acuity and visual field. During the follow-up period,
      tumour recurrence occurred in 1 patient (9%) following complete tumour removal,
      in 8 patients (57%) after subtotal removal, and in 6 patients (55%) after partial
      removal. The range of follow-up was between 2 and 14 years. CONCLUSIONS: On the
      basis of our own experience we conclude that complete removal of the
      craniopharyngioma leads to the best outcome in terms of survival time and period
      free of recurrence. Clinical and radiological observation of the patients who
      underwent nonradical operation seems to be reasonable. In cases with tumour
      recurrence, reoperation and subsequent radiotherapy are advisable.

PMID- 17199174
TI  - [Operative treatment of anterior cranial base meningiomas].
AB  - BACKGROUND AND PURPOSE: The aim of the study is to assess outcome of surgical
      treatment of anterior cranial base meningiomas with special emphasis on the
      evaluation of visual skills after surgery. MATERIALS AND METHODS: A series of 52
      consecutive patients operated on for anterior cranial base meningioma in the last
      ten years is reported. 18 patients had decreased visual acuity on admission, 6
      experienced blindness in one eye, and 4 were totally blind; defects of visual
      fields were found in 17 patients. Primary optic atrophy and secondary optic
      atrophy were noted in fundcoscopy in 20 and 2 patients, respectively.
      Papilloedema was found in 3 patients. RESULTS: Meningiomas were resected
      radically (Simpson I surgery) in 13 patients and in 34 patients Simpson II
      surgery with coagulation of the dural attachment was made; meningiomas were
      partially removed in 5 patients (Simpson IV surgery). In one patient dense
      hemiparesis occurred after the surgery, and 3 others presented adynamic syndrome,
      one of whom made a good recovery in follow-up examination. Two patients died: the
      first one due to a large brain oedema and the second one due to myocardial
      infarction after uncomplicated postoperative course. The postoperative course in
      the other 46 patients was uneventful with good outcome. Visual acuity improved in
      15 cases and did not change in 10 patients; visual acuity further decreased in 3
      patients. CONCLUSIONS: Visual recovery is significantly related to preoperative
      visual acuity values of no less than 0.3 D and to the presence of normal optic
      discs on fundoscopic examination additionally tumour size less than 3.5 cm
      favourably affects visual prognosis in meningiomas of tuberculum sellae.

PMID- 17199175
TI  - [Early postoperative assessment of cognitive functions after stereotactic
      pallidotomy in patients with primary dystonia - preliminary results].
AB  - BACKGROUND AND PURPOSE: The newest studies notify that globus pallidus, besides
      the motor control, plays an important role in cognitive functioning of: memory,
      attention, linguistic skills, visuospatial ability, and executive functions.
      Stereotactic pallidotomy (the lesion of the motor region of the globus pallidus)
      is one of the surgery options that is used in the treatment of the primary
      dystonia. Motor region is located in the postero-ventral part of the internal
      globus pallidus. The goal of the study was to assess of the influence of
      pallidotomy on cognitive functioning in the group of patients suffering from the
      primary dystonia. MATERIAL AND METHODS: Eighteen patients diagnosed with primary
      dystonia were treated by stereotactic pallidotomy and they were investigated
      neuropsychologically. The study was performed between March 2004 and February
      2005. Neuropsychological assessment was conducted 1-2 days prior to operation and
      2 days following the surgery. The clinical course of the cognitive functions and
      emotional status were assessed by the following neuropsychological tests: Mini
      Mental State Examination (MMSE), Trail Making Test A and B (TMT A and B), Stroop
      Color-Word Interference Test, N-back Test, Auditory Verbal Learning Test (AVLT),
      Benton Visual Retention Test (BVRT), Wisconsin Card Sorting Test (WCST), Beck
      Depression Inventory (BDI), Montgomery-Asberg Depression Rating Scale (MADRS).
      RESULTS: The statistically significant differences have been obtained between the
      results before and after the surgery in the depression scales: BDI (p<0.02) and
      in MADRS (p<0.01). None of the neuropsychological tests revealed significant
      differences between the results before and after the surgery. The only trend
      (p=0.06-0.07) was noted between results of AVLT before and after the surgery. The
      average results were worse after the surgery in the first, fifth and sixth
      attempt of the reply. CONCLUSIONS: Stereotactic pallidotomy has not significantly
      changed cognitive functions in the patients suffering from primary dystonia.
      Whereas, the emotional state has significantly improved in consequence of the
      applying surgery. Stereotactic pallidotomy in primary dystonia seems to be a
      treatment option safe for the patients' cognitive functions.

PMID- 17199176
TI  - [Surgical treatment of spondylitic spine with transpedicular stabilisation].
AB  - BACKGROUND AND PURPOSE: Widespread use of antibiotics resulted in considerable
      reduction of spondylitis, but despite that progress there are some cases where
      conservative treatment has failed. In these patients surgical intervention should
      be carefully considered. Early surgery in patients with increasing neurological
      deficits causes the uncertainty which exists in relation to possible
      complications. Fewer doubts are associated with surgical treatment of late
      consequences (spine deformity, instability, etc). The goal of this study was to
      present indications for surgery, operative techniques of transpedicular
      stabilization and results of treatment of thoracic and lumbar spondylitis.
      MATERIAL AND METHODS: Clinical analysis includes 18 patients with spondylitis
      treated in the Department of Neurosurgery and Neurotraumatology University of
      Medical Sciences in Poznan between 1997 and 2004. There were 7 males (39%) and 11
      females (61%) in the study group, and their mean age was 57+/-10 years (range 49
      69). Spondylitis within thoracic segments was found in 15 (83%) cases and 3 (17%)
      patients had spondylitis within lumbar segments. Indications for early surgical
      intervention included increasing neurological symptoms, spine instability and
      failed conservative treatment. All patients underwent transpedicular
      stabilization following medulla and nerve root decompression. RESULTS: Non
      specific inflammation was observed in 14 (78%) cases, and specific inflammation
      was discovered in 4 (22%) cases (bacteriological and histopathological findings).
      Very good and satisfactory results were achieved in 16 (89%) patients.
      Complications occurred in 4 (22%) patients. CONCLUSIONS: Spondylitic spine
      surgery limits inflammatory reaction, strengthens diagnosis, repairs vertebral
      column stability and improves neurological condition. Transpedicular
      stabilization is an effective method of achieving of internal spondylodesis.

PMID- 17199177
TI  - [Usefulness of the antisense and triplex anti-IGF-1 techniques for postoperative
      cellular gene therapy of malignant gliomas expressing IGF-1].
AB  - BACKGROUND AND PURPOSE: The aim of the study was to estimate the usefulness of
      the antineoplastic vaccination in treatment of malignant brain tumors. According
      to medical knowledge there is no cure for this kind of tumors. MATERIAL AND
      METHODS: Between 2001 and 2005, ten patients suffering from malignant glial
      tumors were treated. There were 5 male and 5 female individuals, aged from 17 to
      76 (mean age: 40.8 years). The histopathological examination showed 4 cases of
      glioblastoma and 6 cases of anaplastic astrocytoma. Initially, patients were
      operated on with dissection of 1 cm(3) of the most representative part of tumor.
      The neoplasm cells were cultured, transfected with episomal pMT EP vector
      (expressing alternatively oligonucleotide sequence forming triple helix with IGF
      I gene or antisense against IGF-1 mRNA), re-cultured, irradiated and resuspended
      in medium to prepare antineoplastic vaccine. The patients were vaccinated
      subcutaneously. We examined peripheral blood lymphocyte subsets to assess the
      immunological response of the patients. RESULTS: We observed prolongation of the
      survival time to 21.7 months compared to 9-11 months observed in literature. The
      patients were additionally treated oncologically with radiotherapy and
      chemotherapy (temozolomide) according to the reasonable indications. Therefore,
      the comprehensive assessment of the genotherapy as the supplemental monotherapy
      was impossible. CONCLUSIONS: The method of treatment used in this study prolongs
      the survival time of patients with high-grade gliomas of the central nervous
      system. This gene therapy needs further investigations as a method of oncological
      monotherapy of brain malignant gliomas.

PMID- 17199178
TI  - [Molecular mechanisms of levodopa action in animal models of Parkinson's
      disease].
AB  - Parkinson's disease is a progressive neurodegenerative movement disorder,
      affecting mainly the elderly. One of the most important hallmarks of Parkinson's
      disease is the loss of neuronal cell bodies containing neuromelanin in the
      substantia nigra zona compacta, and subsequently, loss of dopamine terminals in
      basal ganglia nuclei of the brain. The discovery by Hornykiewicz and co-workers
      that levodopa could successfully treat Parkinson's disease in humans was one of
      the most important events of medicine in the 20th century. Since loss of
      nigrostriatal dopaminergic function is the basic underlying pathophysiology of
      this disease, drugs that enhance dopaminergic function in the striatum, including
      the exogenous precursor levodopa, remain the most effective symptomatic agents in
      the treatment of Parkinson's disease. However, there are some areas of
      controversy about levodopa-evoked motor complications (dyskinesias, on-off
      phenomena) as well as neuroprotective or neurotoxic activity of this drug, etc.
      In this article the authors try to clarify the molecular mechanisms involved in
      levodopa action, such as volume transmission - a crucial process for successful
      levodopa therapy, evidence that serotoninergic neurons may accumulate levodopa
      and convert it into dopamine as well as some aspects of neuroprotective action of
      levodopa.

PMID- 17199179
TI  - Co-existing spinal canal tumours and CADASIL - a diagnostic challenge.
AB  - We would like to present a case of a 51-year-old patient with two rare co
      existing diseases. The patient was suffering from two tumours in the lumbar
      region of the spinal canal, which caused development of hydrocephalus. Diffuse
      white matter hyperintensities (WMH) were observed in our patient's brain imaging.
      She was also suffering from headaches and she had two mild strokes. We performed
      some further diagnostic procedures and found out that the patient was suffering
      from CADASIL. CADASIL was confirmed by both ultrastructural analysis and genetic
      testing.

PMID- 17199180
TI  - [Multifocal ischaemic stroke and myocardial infarction in a woman with occult
      lung cancer complicated with chronic DIC and thrombotic endocarditis].
AB  - Ischaemic stroke in thromboembolic mechanism may be a first sign of neoplastic
      disease, as in the presented case of a 56-year-old woman. Progressive
      trombocytopenia, anaemia with reticulocytosis and schistocytes in peripheral
      blood smear, elevated serum LDH activity as well as coexisting myocardial
      infarction initially suggested Moschcowitz syndrome. However, plasma exchange did
      not improve her neurological status and D-dimer values increase in subsequent
      evaluations indicated chronic DIC. At the same time, on transesophageal
      echocardiography, thrombotic endocarditis was diagnosed. Screening for cancer
      showed high CA 125 marker and chest computed tomography revealed lung tumor, not
      visible on earlier chest X-ray. In further treatment she underwent palliative
      radiotherapy and continued low molecular weight heparin. The neoplastic process
      had an unfavorable course and she died after four months. The authors point out
      that in case of multifocal ischaemic stroke and coexistent thrombocytopenia,
      neoplastic hypercoagulable state and thrombotic endocarditis should be
      considered.

PMID- 17199181
TI  - Widespread subcutaneous haematoma after thrombolytic therapy in stroke patients.
      Mild falls at stroke onset may be dangerous.
AB  - Recombinant tissue Plasminogen Activator (rtPA) is one of the more and more often
      used therapies in ischemic stroke. Main adverse effect of rtPA could be bleeding
      in different anatomical sites. Onset of the stroke is often associated with falls
      due to sudden limb weakness. Mild trauma can be not reported by patients and
      their families and can leave no visible signs on the skin. Thrombolytic therapy
      given in such cases can cause potentially dangerous complication such as
      subcutaneous or subfascial hematoma. The article presents two cases of patients
      with ischemic stroke who received thrombolytic therapy with subsequent
      complication of wide-spread subcutaneous hematomas.

PMID- 17199182
TI  - Ultrasound in abdominal and soft-tissue childhood PTLD (post-transplant
      lymphoproliferative disease).
AB  - AIM: Post-transplant lymphoproliferative disease (PTLD) is a rare condition,
      which should be well known to all paediatric medical facilities dealing with bone
      marrow and solid organ transplantation. The spectrum and the primary detecting
      modality of the initial imaging findings in paediatric transplant recipients with
      abdominal and soft-tissue PTLD should be studied retrospectively. METHOD: 7
      children/adolescents (female: 4, male: 3; age: 3 - 19 yrs.; study period: 7 yrs.)
      after heart (5), kidney (1) or liver (1) transplantation were evaluated regarding
      their initial clinical and imaging findings of PTLD. RESULTS: 6 patients had a
      latent Epstein-Barr virus (EBV) infection. PTLD presented with clinical symptoms
      in only 5 patients (ileus: 2, soft-tissue swelling: 2, intussusception: 1) and
      was detected on routine abdominal ultrasound (US) controls in the remaining
      patients. US was the primary imaging modality in all children and led to
      suspecting PTLD in 6 patients. In the seventh case, US had been misinterpreted
      first. Compared to US, additional magnetic resonance imaging (MRI) and/or
      computed tomography (CT) better demonstrated the extent of the disease in 3
      children, but were even inferior in another 3. There was no completely false
      negative US examination during the study period. CONCLUSION: US is reliable for
      detecting as well as excluding abdominal and soft-tissue PTLD in paediatric
      patients after solid-organ transplantation and might even be superior to MRI/CT.
      Therefore, all patients with an increased risk of developing PTLD should be
      closely monitored by ultrasound. MRI/CT may be reserved for supplementary imaging
      in cases incomplete or equivocal on US, but are primarily essential in all
      patients with a localisation of PTLD not accessible by US.

PMID- 17199183
TI  - [Backache as main symptom of unknown primary cancer syndrome with a particularly
      severe course].

PMID- 17199184
TI  - [Cardiac infiltration as complication of cutaneous T-lymphoblastic non-Hodgkin's
      lymphoma].

PMID- 17199185
TI  - [Abernethy malformation -- congenital aplasia of the portal vein a 29-year-old
      patient].

PMID- 17199186
TI  - [Extrarenal parametrial angiomyolipoma of the ovarian vein with extension into
      the right atrium].

PMID- 17199188
TI  - [Refractive aspects of modern cataract surgery].
AB  - OBJECTIVE: Modern cataract surgery is a refractive procedure whereby one
      basically can achieve the targeted postoperative refraction. METHODS: To achieve
      this goal, according to the patient's wishes, biometry, mathematical calculation
      of IOL power and astigmatism management are important factors. On the other hand,
      multifarious developments in intraocular lens technology also contribute to this
      target. RESULTS: The individual choice of incision (on axis surgery: incision in
      the steeper meridian, length, shape and location concerning cornea or sclera)
      reduces the preoperatively existing astigmatism. Biometry with personalised data
      and formulas of the third generation are important factors to achieve the
      targeted refraction. In addition to this, the development of manifold lens
      designs in the last years to improve intraocular lens quality has enabled
      progress within various domains, for example, the use of optimised intraocular
      lenses to compensate corneal aberration, the implantation of toric lenses for
      corrections of higher pre-existing corneal astigmatism or the use of phacic
      intraocular lenses to correct higher ametropia. CONCLUSION: Patient satisfaction
      postoperatively depends on the precise refractive result as desired. With our
      current operative and technical possibilities we are able to achieve this with
      high probability and safety.

PMID- 17199189
TI  - [Protein kinase C isoforms in corneal epithelium and endothelium].
AB  - BACKGROUND: Protein kinase C (PKC) plays a key role in cell metabolism. Three
      subgroups and 12 isoforms have been isolated so far, catalysing specific
      functions in cell metabolism. The demonstration of PKC subtypes in corneal tissue
      has been inconsistent. The aim of this study was to verify the expression of
      several PKC subgroups and isoforms in human and bovine corneal epithelial and
      endothelial cells. MATERIALS AND METHODS: PKC subgroups and isoforms were studied
      using polyclonal antibodies. RESULTS: Antibodies to PKC-alpha, -delta, -epsilon
      and -zeta, representing all three PKC subgroups, bound in human and bovine
      corneal epithelium and endothelium. No binding was found for antibodies to PKC
      beta2. CONCLUSIONS: For the first time the presence of all three PKC subgroups
      was demonstrated in human and bovine corneal epithelial and endothelial cells.
      Further studies are needed to show the role of these subgroups in cellular
      functions such as cell proliferation and differentiation.

PMID- 17199190
TI  - [Corneal wound healing after experimental penetrating keratoplasty after excimer
      laser trephination in free form].
AB  - BACKGROUND: The postoperative clinical course after penetrating keratoplasty and
      trephination in free form using a guided excimer laser beam has been published
      before. Here the findings of light-microscopy comparing corneal wound healing
      after experimental penetrating keratoplasty after laser trephination and after
      conventional mechanical trephination are presented. MATERIALS AND METHODS:
      Homologous penetrating keratoplasty was performed on 12 NZW rabbits (6 animals
      with mechanical trephination, 6 animals with excimer laser trephination). The
      cutting edges achieved by both trephination techniques were examined by light
      microscopy in the remaining donor rings. During the postoperative follow-up
      animals were sacrificed at 3 and 6 weeks and at 3 months. Corneal specimens were
      retrieved and corneal healing processes were evaluated by light microscopy.
      RESULTS: The cutting edges of corneal excisions with the excimer laser
      demonstrated a high precision with only minimal collateral damage to adjacent
      tissue structures. At the different intervals both trephination groups
      demonstrated comparable stages of corneal wound healing regarding epithelial
      regeneration, stromal fibroblast migration with collagen synthesis and Descemet
      repair by endothelial synthesis of basement membrane. After 6 months corneal
      specimens of both groups demonstrated complete healing with nearly parallel
      orientation of newly synthesised collagen lamellae. Corneal thickness in the
      wound areas did not differ significantly from normal corneal tissue. CONCLUSIONS:
      Experimental follow-up studies to evaluate the feasibility of the developed
      technology of laser trephination in the living eye have shown no differences
      between conventional mechanical and excimer laser trephination with a guided
      beam. The present histology study also does not demonstrate any significant
      differences in corneal wound healing between the two trephination groups.
      Although excimer laser trephination along metal masks has now been established
      for several years, the here presented technique for trephination with
      individualised transplant geometries appears to be a valuable addition to the
      surgical repertoire in the presence of selected corneal pathologies.

PMID- 17199191
TI  - [Influence of intraoperative pupil diameter and nuclear grade due to
      complications during Aqualase phacoemulsification].
AB  - PURPOSE: The aim of this study was to make an evaluation of the frequency of
      intraoperative complications during Aqualase phacoemulsification and correlate it
      to different intraoperative pupil diameters and nuclear grades. METHODS: Aqualase
      phacoemulsification was performed in 23 eyes without retinal or optic disc
      pathology in 23 unselected patients (15 women and 8 men) who underwent out
      patient cataract surgery. Nuclear grade, intraoperative pupil diameters and
      complications were recorded. The correlation of intraoperative complications with
      intraoperative pupil diameter and nuclear grade was determined using "Fisher's
      exact" test. RESULTS: The average age of our patients was 70.3 (+/- 12.5) years,
      the mean best spectacle-corrected visual acuity (BSCVA) preoperatively was 0.39
      (+/- 0.15) and the mean BSCVA postoperatively was 0.79 (+/- 0.13). The mean aqua
      time was 3.11 s (+/- 1.55 s) with maximum nuclear sclerosis of up to grade 3
      (mean nuclear sclerosis 1.9). The aqua time correlated with the nuclear sclerosis
      (r = 0.90). The mean intraoperative pupil diameter was 7.2 (+/- 0.7) mm. In 2 of
      3 patients with an intraoperative pupil diameter of 6 mm, iris touch occurred
      intraoperatively. There were no other intra- or postoperative complications. The
      frequency of iris touch was statistically significantly higher for reduced pupil
      diameters (p = 0.01). The nuclear grade with a maximum of 3 was without
      statistical significance to iris touch frequency (p > 0.05). CONCLUSIONS: The
      number of iris traumas is significantly higher when the intraoperative pupil
      diameter is reduced. The iris should be protected in these cases. A prospective,
      randomised study should be performed to compare the number of intraoperative
      complications between ultrasound and Aqualase phacoemulsification.

PMID- 17199192
TI  - [The Salzburg-Moorfields Collaborative Glaucoma Study: first results of the
      prevalence and 5-year incidences in this prospective, population-based
      longitudinal study].
AB  - BACKGROUND: This prospective, population-based longitudinal study describes
      prevalences and 5-year incidences of individuals with normal findings, ocular
      hypertension (OHT) and primary open-angle glaucoma (POAG) admitted to the
      Salzburg-Moorfields Collaborative Glaucoma Study (SMCGS). PATIENTS AND METHODS:
      The SMCGS is embedded in a government-supported glaucoma blindness prevention
      programme in Salzburg (Austria) which is designed for a minimum of 10-years
      follow-up. Each subject receives a complete ophthalmological examination. In
      total, the findings of 853 subjects with complete data sets were analysed and
      evaluated. RESULTS: The prevalence of participants with normal findings was 75 %
      (95 % CI: 72 - 78 %) at the initial examination, decreasing to 64 % (95 % CI: 60 
      67 %) at the 5-year follow-up. The prevalence of OHT at the initial exam of 2.3
      % (95 % CI: 1.4 - 3.6 %) increased to 3.5 % (95 % CI: 2.4 - 5.0 %) at the 5-year
      follow-up exam with an incidence of 1.2 % (95 % CI: 0.6 - 2.2 %). Finally, the
      prevalence of POAG of 0.6 % (95 % CI: 0.2 - 1.4 %) increased to 1.6 % (0.9 - 2.7
      %) at the 5-year exam which corresponds to a 5-year incidence of POAG of 1.0 %
      (0.5 - 2.0 %). CONCLUSION: The prevalence of POAG increases statistically
      significantly when compared at the initial and 5-year follow up exam (p = 0,002).
      Our results confirm the positive relation between age and the prevalence of POAG
      (odds ratio = 0.89, 95 % CI: 0.81 - 0.98). The prevalence and 5-year incidence
      rates in this glaucoma prevention study are similar to those of other population
      based studies.

PMID- 17199193
TI  - [Comparative study of treatment of the dry eye syndrome due to disturbances of
      the tear film lipid layer with lipid-containing tear substitutes].
AB  - BACKGROUND: A deficiency in the tear film lipid layer is aetiological in about 80
      % of the patients suffering from dry eye, which results in excessive evaporation
      (so-called hyperevaporative dry eye). The treatment with conventional artificial
      tears did not prove to be successful here. In this study the treatment with two
      tear substitutes containing lipids were set in contrast with each other. MATERIAL
      AND METHODS: The randomised, controlled, multicentre cross-over study included 74
      patients suffering from dry eye caused by a deficiency of the tear film lipid
      layer, which were organised into two groups. Group A (n = 38) was treated for the
      first 6 weeks with a liposomal eye spray (Tears Again), while the patients of the
      group of B (n = 36) were treated with an eye gel containing triglycerides
      (Liposic) in the same period. After 6 weeks the crossover was performed. The
      patients were treated in the following 6 weeks with the product which was not
      used before. Control examinations by masked examiners took place at the beginning
      of the study as well as after 6 and 12 weeks, considering the following
      parameters: eyelid edge-parallel conjunctival folds (LIPCOF), BREAK UP time
      (BUT), Schimer-I test, measurement of the tear meniscus, investigation of the
      edges of eyelid and visual acuity. In addition. the subjective feelings of the
      patients were also determined by means of questionnaires. RESULTS: At the
      beginning of the study the two groups did not differ significantly with respect
      to the initial values. After the first treatment period the improvement of the
      examined parameters LIPCOF, BUT, Schirmer, visual acuity and inflammation of the
      lid margin in group A (eye spray) proved to be significantly superior in
      comparison to group B (eye gel). The results of the second treatment period after
      the crossover were similar and showed an analogous supremacy of the liposomal eye
      spray. The interviews with the patients revealed that the subjective evaluation
      concerning efficacy and compatibility of the eye spray turned out to be
      explicitly more favourable than that concerning the eye gel. 74.6 % of the
      patients favoured the application as an eye spray onto the closed eyelids over
      the eye gel into the conjunctival sac. 62.5 % of the patients rated the liposomal
      eye spray to be better all in all, 12.5 % rated that both preparations are equal
      and 25 % favoured the eye gel. CONCLUSIONS: The treatment with phospholipids
      liposomes shows statistically significant clinical advantages and proves to be
      favourably and explicitly superior compared to the conventional standard
      treatment all in all.

PMID- 17199194
TI  - [Nd:YAG Laser for retrohyaloidal haemorrhage after retinal branch vein
      occlusion].
AB  - BACKGROUND: A retrohyaloidal haemorrhage can be caused by different underlying
      diseases. Usually dense haemorrhages are treated by early vitrectomy. We want to
      report the successful treatment of a retrohyaloidal haemorrhage by means of
      Nd:YAG laser membranotomy. MATERIALS AND METHODS: A 47-year-old man noticed two
      weeks before presentation a sudden visual loss in the left eye. Visual acuity on
      the first visit was c. c. 20/32 OD and c. c. 20/400 ex. OS. Dilated fundus
      examination of the left eye showed multiple intraretinal haemorrhages in the
      superior periphery and a dense retrohyaloidal haemorrhage over the macula.
      Anamnestic risk factors for ocular bleeding were systemic hypertension in
      connection with adiposity. RESULTS: A retinal branch vein occlusion with
      retrohyaloidal haemorrhage due to systemic hypertension was diagnosed. To drain
      the retrohyaloidal haemorrhage into the vitreous an Nd:YAG laser membranotomy of
      the anterior surface of the haemorrhage was performed. Visual acuity increased to
      20/100 within 30 min. CONCLUSION: Possible therapeutic options to manage
      retrohyaloidal haemorrhages are observation, primary vitrectomy and Nd:YAG laser
      membranotomy. The presented case shows laser membranotomy to be a promising
      possibility for a rapid resolution of retrohyaloidal haemorrhage in selected
      patients.

PMID- 17199195
TI  - [Photodynamic therapy in classic chorioidal neovascularisation in patients with
      angioid streaks].
AB  - BACKGROUND: The development of subfoveal or juxtafoveal choroidal
      neovascularisation (CNV) secondary to angioid streaks poses a great therapeutic
      challenge. The relevance of the photodynamic therapy (PDT) with verteporfin is
      still unclear. We present the functional and anatomic outcome of 5 patients with
      CNV due to angioid streaks treated by PDT. METHODS: We reviewed 4 eyes with
      subfoveal and 1 eye with juxtafoveal CNV in angioid streaks of 5 patients (4
      male, 1 female) treated by PDT between 2000 and 2005. The age ranged from 20 to
      74 years (median 63 years). PDT was performed according to the TAP criteria. Best
      corrected visual acuity was measured using ETDRS charts. RESULTS: Visual acuity
      (VA) ranged between 20/63 and 20/32 (median 20/32) at first presentation and
      between 20/2000 (counting fingers) and 20/20 (median 20/400) at last
      presentation. Median follow-up time was 13 months with a range of 5 to 45 months.
      The visual acuity in one patient decreased by 1 line, in 3 patients by more than
      6 lines whereas VA of one patient (juxtafoveal CNV) increased by 2 lines. PDT was
      repeated in 4 patients once because of persistent leakage and in one patient
      twice. At the end of the follow-up period a fibrous disciform lesion was seen in
      4 patients, in one patient subfoveal membranectomy was performed due to a
      recurrence. CONCLUSIONS: In general, PDT of CNV is less favourable in angioid
      streaks than in AMD. However, in the natural course final VA is counting fingers.
      Therefore the good results of individual cases justify the PDT under a critical
      indication.

PMID- 17199196
TI  - [OCT and PVEP examination in eyes with visible idiopathic optic disc drusen].
AB  - OBJECTIVES: It has been reported that the presence of optic disc drusen is mostly
      not associated with a reduction in function of the visual organ. At present by
      using more precise diagnostic tools it is possible to find more pathology. The
      aim of the study was to evaluate changes in peripapillar RNFL thickness and VEP
      parameters in a group of patients at the Department of Ophthalmology in Poznan,
      with diagnosed visible idiopathic optic disc drusen. MATERIALS AND METHODS: We
      have reviewed the medical records of 7 patients (5 women and 2 men) age range 43 
      61 years, mean age 51 years, with idiopathic visible optic disc drusen confirmed
      by ultrasound B scan. RNFL were measured with use of an OCT system (Stratus,
      Zeiss): fast RNFL thickness = 3.4. VEP were evaluated with use of a 60 pattern.
      RESULTS: In all patients OCT has shown a thinnig of peripapillar retinal nerve
      fiber layer. The lowest values were found in the superior and inferior quadrants.
      In 9 eyes we recorded VEPs with prolonged latency P100 from 117.2 - 135.8 msec,
      with a small reduction of the P100 amplitude. CONCLUSIONS: Idiopathic visible
      optic disc drusen are associated with changes in peripapillar RNFL thickness,
      especially in the superior and inferior quadrants. The anatomic pathology is
      related to functional abnormalities as confirmed with VEP. Detection of this type
      of drusen should be an indication to search for possible RNFL and VEP pathologies
      and to monitor their possible progression.

PMID- 17199197
TI  - [Welcome address by the president of the Federal Chamber of Physicians at the
      opening ceremony of the 56th OGD Congress 2006].

PMID- 17199198
TI  - [Healing without confidence? On the need for mutual confidence in medicine].

PMID- 17199199
TI  - [Cross-border cooperation in Europe: what are Euregios?].
AB  - In cross-border cooperation, much importance has been attributed to the so-called
      "Euregios", synonymously also called "Euroregions". These are cross-border
      structures in which, above all, local and regional authorities have joined
      together across one or several national borders. As early as 1958, the first
      Euregio was established along the German-Dutch border. Meanwhile many other
      Euregios have been set up. Euregios provide the testing ground for pilot projects
      to examine practical solutions of cooperation. Euregios are therefore also called
      "laboratories of Europe" or "testing laboratories of European integration". Also
      in the health sector, several cross-border projects are being and have already
      been carried out. According to what has been found out so far, above all Euregios
      with long years of experience in cross-border cooperation seem to commit
      themselves to the health issue. A huge number of the projects is co-financed by
      the European Union. Compared to other thematic areas, in some border regions the
      health issue has, on the whole been, underrepresented in cross-border
      cooperation. In this respect, there is potential for development. Information on
      existing projects as well as their experiences can facilitate the successful
      implementation of health-relevant cross-border projects also in those regions
      which have up to now not carried out any or only a few projects of this kind. The
      EU-funded Euregio project, carried out by logd NRW, is the first project in which
      a systematic inventory analysis of cross-border health care projects will be
      drawn up.

PMID- 17199200
TI  - [EUREGIO-projekt MRSA-net Twente/Munsterland. Creation of a regional network to
      combat MRSA].
AB  - Over the last years, Germany has observed an increase in the prevalence of
      methicillin-resistant Staphylococcus (MRSA) in all S. aureus isolates from 2 % to
      about 25 % whereas in The Netherlands this proportion has continuously been kept
      below 1 % thanks to a consistent "search & destroy" policy. Both countries
      increasingly register so-called community-acquired (CA) MRSA which are a threat
      also to the healthy population without any known risk factor for MRSA
      carriership. The EUREGIO project "MRSA-net Twente/Munsterland" has made it its
      main goal to set up a German-Dutch network serving as a basis for a quality
      association which includes all those who are actively involved in health care
      provision on both sides of the border and to implement a coordinated strategy for
      MRSA control and prevention. The project is being carried out with the financial
      support of the European Union under the INTERREG-IIIA Community initiative and of
      the Ministry of Economics of the State of North Rhine-Westphalia. The
      epidemiological backbone of the MRSA-net is a genetic-based MRSA typing strategy
      (spa-typing) which has been developed by the Institute for Hygiene, University
      Hospital, Munster and which allows regional and cross-border comparability of
      laboratory results. The Faculty of Behavioural Sciences of the University of
      Twente examines MRSA hygiene protocols with regard to their acceptability and
      realisability with the intention of developing user-friendly, target group
      oriented MRSA protocols for the EUREGIO. The health departments involved in the
      project play a central role in the coordination of the network partners in the
      municipalities. By performing their function of surveillance in accordance with
      Sections 23 and 36 of the Infectious Disease Control Act they provide an
      important contribution to enhancing MRSA control and prevention strategies.
      Thanks to its cross-border cooperation and exchange of knowledge and technology
      the EUREGIO project "MRSA-net" contributes to controlling the proliferation of
      MRSA in the EUREGIO and thus to removing obstacles to the free cross-border
      movement of patients and personnel.

PMID- 17199201
TI  - [Surveillance of acute respiratory illnesses (ARI) in Lower Saxony: first
      experience from the years 2005-2006].
AB  - In the context of influenza pandemic preparedness planning, a surveillance system
      for influenza and other acute respiratory illnesses was implemented in Lower
      Saxony at the beginning of the influenza season 2004/2005 and coordinated by the
      Governmental Institute of Public Health of Lower Saxony. This surveillance system
      represents an addition to already existing national monitoring systems. The goal
      of this surveillance system is to have available prompt information on the
      beginning, course and end of the influenza season and to recognise the spectrum
      of pathogens and identify outbreaks of other viral acute respiratory illnesses
      (ARI). For this purpose an all-season surveillance was established consisting of
      two supplementary modules. The first module is a symptom-oriented surveillance of
      acute respiratory illnesses in children of pre-school day care facilities. In the
      second module a virological surveillance in co-operation with selected medical
      practices was established. While the temporal course and burden of ARI in all
      Lower Saxony can be assessed by the surveillance of children in the day-care
      facilities in a sensitive, but less specific way, the virological surveillance
      provides highly specific information on the prevailing pathogens in ARI patients
      at a certain time. This information, in return, gives an indication about the
      responsible pathogens causing ARI in children of the day-care facilities. The
      first experience with these two complementary surveillance modules shows that in
      Lower Saxony a well accepted, prompt and meaningful monitoring system is
      available for the recognition and description of the occurrence of ARI and
      concomitantly of influenza. An extension of this surveillance to other pathogens
      or disease scenarios is possible.

PMID- 17199202
TI  - [Anonymous STD counselling versus mandatory checks for prostitutes--what is
      effective in STD prevention?].
AB  - BACKGROUND: When in 2001 in Germany the new act for control of infectious
      diseases came into force, mandatory checks for prostitutes were abolished. The
      consequences of this paradigm shift in STD prevention are being judged
      controversially even today. The public health department of the city of Cologne,
      like others, adapted its programme, staff, equipment, and diagnostic procedures
      to the new requirements. The department for venereal disease control was
      converted into a walk-in-clinic for STD and now forms part of a comprehensive STD
      and Aids prevention unit. The present article illustrates the changes by
      comparing the clients and the STD numbers of the years 1994 and 2004. METHOD: The
      following data were compared: number of consultations, number of clients
      regarding sex, occupation in sex business, health insurance, national or ethnic
      background, frequency of consultation, number of STD. RESULTS: In 1994, almost
      all clients of the department for venereal disease control were female
      prostitutes. 74% of them worked in established sex business venues with a high
      grade of professionalism, few STD cases were diagnosed. In 2004, the STD clinic
      was open for anybody considered to be at risk and not having access to the
      regular health care system. Only 49% of the patients were prostitutes, either
      female or male. 25% of the clients were male. 68% of the patients were migrants,
      many of them without any legal status and without any access to regular health
      care. A high number of acute STD and subsequent disorders that required treatment
      was registered. Besides the STD-related services, a great need for gynaecological
      and urological differential diagnostics as well as a high demand for counselling
      and provision of other problems of sexual health were observed. DISCUSSION: The
      data show that an STD department providing comprehensive services anonymously and
      free of charge will reach a broader range of highly vulnerable persons in
      comparison with an obligatory VD check of prostitutes. The high numbers of STD
      and STD-related disorders demonstrate the improved effectiveness of the new
      service.

PMID- 17199203
TI  - [Are we testing the right people? Results of a patient questionnaire in the STD
      and HIV counselling office of the local health authority in the city of Cologne].
AB  - BACKGROUND: HIV testing and counselling is offered free of charge in most local
      health offices in Germany. During 2003, a survey was performed among German
      speaking clients of the Cologne local health office to look at socio-demographic
      background, reasons for testing and sexual risk behaviour. METHODS: All German
      speaking clients attending the HIV counselling office from March to July 2003
      were asked to fill in an anonymous standardised questionnaire. Questions included
      demographic characteristics, social status, STI history, reasons for HIV testing,
      sexual orientation and number of sexual partners. Data were compared to the
      general Cologne population regarding demographic characteristics. Female
      respondents were compared to heterosexual men and men who have sex with men
      (MSM); German respondents were compared to migrants using SPSS 14.0. RESULTS: A
      total of 457 female and 488 male clients participated (response rate 93.9 %).
      Average age was 28.4 years. Of all participants, 17.7 % were of non-German
      origin. The respondents had a high school degree in 80.8 % of the cases compared
      to 33.5 % in the general Koln population (p < 0.001). Among men, 30.2 % were MSM.
      Having a "new partner" or "unprotected sex with a person with unknown HIV status"
      were reported by 483 (39.8 %) and 373 (30.8 %) as reasons for testing. 38.7 % of
      the respondents reported choosing the local health office for HIV testing because
      it was free of charge and 24.5 % because it was anonymous. Women and heterosexual
      men had a median of 1, MSM a median of 3 sexual partners within the past 6 months
      (p < 0.001). Vaccination against hepatitis B was reported by 34.4 % of the
      clients, the proportion was higher among MSM (46.9 % p < 0.001) and lower among
      migrants. 112 (11.9 %) persons reported having had a previous STI. CONCLUSIONS:
      With the exception of MSM, the offer of free and anonymous HIV testing and
      counselling does not reach persons who carry a higher risk for HIV. As the risk
      for STI is higher than for HIV in Germany and there is a low public awareness,
      HIV counselling should be used for comprehensive sexual health counselling and
      include the offer for STI testing, Further outreaching efforts and other settings
      are necessary to reach persons with a low education level and highly vulnerable
      persons.

PMID- 17199204
TI  - [Problems in the vocational rehabilitation of mentally ill subjects--a simple
      procedure to identify persons with an increased risk for premature termination of
      a training programme].
AB  - A small number of young mentally ill persons consumes a disproportionate amount
      of psychiatric service resources. These persons are characterised by emotional
      instability, aggressive or delinquent behaviour, substance misuse and personality
      disorders. They are sometimes referred to as young adult chronic patients (YACP).
      To date there has been no investigation as to what impact this pattern of problem
      behaviour has on vocational rehabilitation. AIM: The aim of this study was to
      find out whether belonging to the YACP group, as determined by an operational
      definition, reduces the outcome of vocational rehabilitation. METHOD: A chart
      review was done of the files of all 174 participants of a 15-month vocational
      training course held between 1.1.1993 and 2.5.1998 in the vocational training
      centre at Cologne. A 15-item score was used to assess YACP status. RESULTS: 30 %
      were classified as high scorers, i. e. YACP. 59 % of the high scorers vs. 22 % of
      the low scorers terminated training prematurely. Of the high scorers who
      completed training, only 47 (vs. 74 % of low scorers) were judged to be able to
      work at the end of training. CONCLUSION: At the very beginning of the vocational
      training persons in need of a highly individualised format can be discerned by a
      few, easy to assess items. Concepts of vocational training should be developed to
      better suit the needs of young mentally ill persons with personality disorders
      and substance abuse.

PMID- 17199205
TI  - [Work, income, intimate relationships: social exclusion of the mentally ill].
AB  - OBJECTIVES: There are no valid data on the social exclusion of mentally ill
      people in Germany. This study analyses the social exclusion of the mentally ill.
      METHODS: With a Scientific Use File on early retirement in 2003, we found a
      nationally representative database for chronically ill persons. The inclusion in
      the working market, the work income and the exclusion of intimate relationships
      of chronically mentally ill people are compared to those of physically disabled
      people. RESULTS: Mentally ill persons are more excluded than physically ill
      persons on all three indicators. This is especially true for persons with
      schizophrenia and alcohol addiction. CONCLUSIONS: Scientifically sound
      instruments such as Supported Employment need to be implemented in Germany, too.

PMID- 17199206
TI  - [Strategies against the stigmatisation of mentally ill subjects and their
      practical realisation in the example of Irrsinnig Menschlich e. V].
AB  - In our society people with mental illness are still stigmatised and exposed to
      various forms of discrimination. Individual and structural discrimination and
      discrimination due to self-stigmatisation can be distinguished. The association
      "Irrsinnig Menschlich" ("Madly human") in Leipzig will serve as a model to
      present approaches to reduce these different kinds of discrimination of mentally
      ill people. The school project "Crazy? So what!" and the film festival
      "Ausnahmezustand" ("state of emergency"), carried out all over Germany in 2006,
      will be described in more detail. The first evaluation of both projects showed a
      reduction of stigmatisation to be possible. Students participating in the project
      tended to decrease their social distance to the mentally ill. These developments
      were not present with the control groups. Although the majority of the audience
      at the film festival either knew somebody who is mentally ill or were themselves
      suffering from a mental illness, the results showed that watching these
      documentaries can result in a reduction of social distance towards mentally ill
      people. Only long-term efforts can make anti-stigma campaigns successful and
      effective. Irrsinnig Menschlich has established the framework for this.

PMID- 17199207
TI  - [Particulate matter in indoor environments--exposure situation in residences,
      schools, pubs, and related recreational spaces].
AB  - Numerous epidemiological studies have been carried out during the last decades
      which have demonstrated an association between the pollution of outside air with
      toxic substances and the occurrence of health-related effects. Against the
      background of these findings, particularly in recent years, the focus of research
      has clearly shifted towards particulate matter (PM), notable fine and ultrafine
      particles. While diverse measurements of PM in the outside air have been
      conducted, only few data on indoor air pollution are available. The concentration
      of PM in the indoor environment is highly variable in time and space due to
      various influencing factors like type of the source, building and room
      characteristics, the activities of users and the airing behaviour. In this
      article we aim to summarise and discuss the exposure situation regarding PM in
      indoor environments. In residences, European studies have found mean PM (2.5)
      values between 10 and 87 microg/m (3). Especially in smokers' homes, a high
      background level was observed, reaching very high concentrations of some hundred
      microg/m (3) when active smoking took place. There are some studies on air
      quality in schools and similar public places which show that exposure to
      particulate matter in these environments is high. The main causes of this
      situation appear to be an insufficient ventilation routine as well as the low
      frequency and quality of cleaning. In combination with the high number of pupils
      in relation to room area and volume and their sometimes high physical activity,
      this leads to a continued resuspension of particles from the room's surfaces. A
      very high concentration of PM can be observed in those recreational places where
      smoking is not prohibited, such as discotheques, pubs and restaurants. Here, the
      mean PM values can reach some hundred microg/m (3). Specific strategies are
      necessary to especially protect the health of non-smokers in such places. Further
      investigations are needed to characterise the composition of indoor particles and
      their toxicological properties compared to particles from outdoor origin.

PMID- 17199208
TI  - [Drinking water data collection and information system in North Rhine-Westphalia.
      Integration of water supply zones].
AB  - To comply with the drinking water regulation act of 2001 and as basis for reports
      to the European Community, North Rhine-Westphalia has defined water supply zones
      and collected the necessary data from local health authorities. The software used
      for drinking water surveillance by the local health authorities and on state
      level has been adapted to the new requirements. In principle, a supply zone in
      NRW means a region where the water comes from one water-works. Under certain
      conditions exceptions are possible. 53 out of 54 local health authorities
      supplied data about water supply zones up to summer 2006. There are 410 water
      supply zones which get their water from around 550 water-works. The number of
      people per supply zone varies between a few hundred and nearly 900,000. Most of
      the supply zones fall within the responsibility of one health authority. Only 37
      supply zones out of 410 contain regions of more than one local health authority.
      27 % of the supply zones get water from three or more water-works, 73% get water
      from one or two water-works. Looking at the other side of the medal, the
      structure is also relatively simple. More than 80% of the water-works deliver
      water into only one supply zone. The definition of water supply zones as chosen
      in NRW has proved to be a good basis for a clear description of the drinking
      water supply. Besides, the definition enables the state to produce reports which
      can link water quality, regions and the supplied persons.

PMID- 17199209
TI  - [Caries prevention with fluoride varnishes among preschool children].
AB  - AIM: The aim of the study was to assess the caries inhibition effect of fluoride
      varnishes among preschool children with high caries risk. At the same time, the
      suitability of this measure should be examined in the frame of group prevention
      programmes in kindergartens. METHOD: This was an examiner-blind, clinically
      controlled 2-year study with 200 randomly selected 2- to 4-year-old preschool
      children with high caries risk. At the baseline, caries-free surfaces, initial
      caries lesions as well as the caries status (dmfs) were recorded. After the
      baseline, all subjects were divided into 3 groups. Subjects of group A received
      every 6 months (altogether four times) applications with the fluoride varnish
      Fluoridin N5 (VOCO GmbH, Cuxhaven, Germany), children of the group B received
      every 6 months (altogether four times) applications with Duraphat (Colgate
      Palmolive GmbH, Hamburg, Germany), while the subjects of group C did not receive
      any fluoride varnish applications and constituted the control group. A final
      examination was performed after two years similar to the baseline. Statistical
      analysis was based on the SPSS programme at a significance level of 95%. RESULTS
      AND CONCLUSIONS: The results confirmed the caries inhibition efficacy of both
      fluoride varnishes. This is shown as well in the almost constant number of caries
      free surfaces and initial caries lesions in the two F-groups during the
      observation period. The caries-free surfaces in group C were significantly
      reduced along with an increase of initial caries lesions. The caries reduction,
      based on the control group, amounted in group A to 56% and in group B to 57%. The
      results documented the caries inhibition effect of both fluoride varnishes which
      are suitable for intensive group prevention programmes for pre-school children.

PMID- 17199210
TI  - New basic science initiatives with the angiotensin II receptor blocker valsartan.
AB  - Angiotensin II (Ang II) plays a key role in the regulation of blood pressure and
      fluid homeostasis. Valsartan is a highly selective Ang II receptor blocker that
      specifically and selectively blocks Ang II at the AT1-receptor. In animal models,
      valsartan has shown positive effects on vasoconstriction, proliferation,
      remodelling, endothelial function and thrombogenesis, inflammation and
      atherosclerosis. These data are likely to be confirmed by the results of current
      clinical trials and valsartan is set to provide improved cardiovascular therapy
      in the future.

PMID- 17199212
TI  - Hypertension and its management: a problem in need of new treatment strategies.
AB  - Although treatments of hypertension have significantly decreased morbidity and
      mortality from cerebrovascular disease, the associated reductions in coronary
      artery disease have been very disappointing. Hypertension is a complex inherited
      syndrome of cardiovascular risk factors, all of which contribute to the
      development of heart disease. Angiotensin II receptor blockers (ARBs), such as
      the highly selective ARB valsartan, provide an alternative treatment strategy to
      address the multiple issues in coronary artery disease. These agents are well
      tolerated and have a once-daily regimen that improves compliance. They bring
      multiple cardiovascular benefits beyond blood pressure (BP) control, such as
      renoprotection and cardiovascular growth reduction.

PMID- 17199211
TI  - Angiotensin receptor blocker selectivity at the AT1- and AT2-receptors:
      conceptual and clinical effects.
AB  - The advent of specific angiotensin II (Ang II) receptor blockers (ARBs) some ten
      years ago has provided substantial information on the specific actions of the AT1
      and AT2-receptors. Most of the early research concentrated on the AT1-receptor,
      and the actions and biological roles of the AT2-receptor are much less well
      characterised. The AT2-receptor is involved in the inhibition of cell
      proliferation, and in cell differentiation and development, regeneration and
      apoptosis. By raising local Ang II concentrations at the AT2-receptor, selective
      blocking of the AT1-receptor may therefore have beneficial effects. This concept
      may be important for antihypertensive therapy and in cardiovascular disease in
      general.

PMID- 17199213
TI  - Valsartan and the renin-angiotensin-aldosterone system: blood pressure control
      and beyond.
AB  - Patients treated for hypertension are still at significantly elevated risk for
      cardiovascular complications when compared with normotensive patients, even when
      on antihypertensive therapy. In all fairness though, a majority of these patients
      have uncontrolled blood pressure. Blocking the renin-angiotensin-aldosterone
      system (RAAS) prevents or reverses cardiac remodelling and improves prognosis in
      cardiovascular disease beyond the effects on blood pressure (BP). Valsartan acts
      by selectively blocking the AT1-receptor and shows similar efficacy and improved
      tolerability compared with ACE inhibitors. This drug may provide additional
      benefits in controlling the cardiovascular complications of hypertension. Results
      of large clinical trials with valsartan, such as VALUE, Val-HEFT, VALIANT and
      ABCD-2V, are eagerly awaited.

PMID- 17199214
TI  - Saving lives: long-term morbidity and mortality trials with selective angiotensin
      receptor blocker therapy.
AB  - Prospective randomised trials have demonstrated convincingly the benefits of drug
      treatment of hypertension. Treatment with conventional antihypertensive agents
      reduces the incidence of cardiovascular events by about that which would be
      expected from epidemiological data for the achieved difference in blood pressure.
      Newer agents, such as angiotensin II receptor blockers, have potential for
      benefits beyond blood pressure reduction. This rationale is under evaluation in a
      number of long-term morbidity and mortality trials which will report over the
      next few years, with the largest, VALUE, due to provide results in 2004. The
      findings from these trials will be decisive in determining the future role of
      this important new class of drugs.

PMID- 17199215
TI  - Cardiac, renal and vascular complications in the diabetic patient.
AB  - Type 2 diabetes has long been known to be associated with an increased risk of
      cardiovascular disease. Patients with type 2 diabetes have also been shown to
      benefit more from antihypertensive therapy than do non-diabetics with
      hypertension. The benefits of aggressive antihypertensive therapy are reflected
      in the recent reduction of blood pressure (BP) targets in international
      guidelines. Drugs acting on the renin-angiotensin-aldosterone system (RAAS) have
      well-documented efficacy, and results from large-scale trials with highly
      selective angiotensin II (Ang II) receptor blockers (ARBs), such as valsartan,
      are awaited. The VALUE trial will provide the largest body of information yet on
      the comparative benefits of using an ARB or calcium channel blocker in
      hypertensive patients with diabetes.

PMID- 17199216
TI  - Improving the prognosis of diabetic patients: evaluating the role of intensive
      versus moderate blood pressure control with selective angiotensin II receptor
      blocker (ARB) therapy.
AB  - The ABCD (Appropriate Blood Pressure Control in Diabetes) and ABCD-2V (Part 2
      with Valsartan) are prospective, randomised clinical trials which will provide
      important data on the impact of intensive vs. moderate blood pressure (BP)
      control on microvascular and macrovascular complications in normotensive and
      hypertensive patients with type 2 diabetes mellitus (DM). The ABCD trial was a
      five-year study that compared the effects of intensive vs. moderate BP control on
      the endpoints of nephropathy, retinopathy, neuropathy, and cardiovascular disease
      events using a calcium channel blocker (CCB) and an angiotensin-converting enzyme
      (ACE) inhibitor as the primary antihypertensive agents. The recently published
      results of the hypertensive cohort of ABCD are reviewed herein. The follow-up
      study, ABCD-2V, is ongoing and was designed to compare intensive vs. moderate BP
      control on the same endpoints as the ABCD study, using the highly selective
      angiotensin II receptor blocker (ARB) valsartan as the primary antihypertensive
      agent. First results of ABCD-2V are expected in 2004. The baseline
      characteristics for the patients enrolled thus far in the hypertensive cohort of
      ABCD-2V are reviewed. These studies will provide insight into the role of
      intensive vs. moderate BP control in the management of normotensive and
      hypertensive patients with type 2 DM.

PMID- 17199217
TI  - New clinical investigations with selective angiotensin II receptor blocker
      therapy in diabetes and renal disease.
AB  - Halting the reduction in glomerular filtration rate (GFR) is the primary aim of
      any treatment of patients presenting with progressive chronic renal failure, a
      very common corollary to diabetes. To improve GFR, the high blood pressure (BP)
      and proteinuria often seen in these patients must both be controlled. These
      symptoms lead not only to progressive loss of renal function, but also to an
      increase in cardiovascular risk. Use of angiotensin-converting enzyme (ACE)
      inhibitors in these patients has been reported to control BP and reduce protein
      excretion and cardiovascular risk. Complete blockade of angiotensin II (Ang II)
      action with the highly selective Ang II receptor blocker (ARB) valsartan, both as
      monotherapy and in combination with ACE inhibitors, is well-tolerated and
      efficacious in patients with renal failure. Unlike ACE inhibition, ARB treatment
      leads to no initial reduction in GFR, thus valsartan may be a better agent for
      the control of BP, with greater renal protection.

PMID- 17199218
TI  - The HF epidemic: the need for new treatment strategies.
AB  - The incidence of heart failure is increasing, particularly in older patients.
      Clinical trials often do not reflect community practice where patients are older
      and have more co-morbid conditions. Therapeutic agents need to be at least
      neutral in their effects on these other conditions. Current therapy in heart
      failure includes angiotensin-converting enzyme (ACE) inhibitors, beta-blockers
      and diuretics, with advanced heart failure patients receiving spironolactone and
      possibly digitalis. Ongoing clinical trials are testing more effective inhibition
      of the renin-angiotensin-aldosterone system (RAAS) with highly selective
      angiotensin II (Ang II) receptor blockers (ARBs) such as valsartan. Future trials
      should study diverse racial groups and the elderly, particularly those with
      preserved systolic function. These should ideally be large multicentre studies
      with internal substudies to examine mechanisms of heart failure.

PMID- 17199219
TI  - Pathological involvement of chymase-dependent angiotensin II formation in the
      development of cardiovascular disease.
AB  - Chymase is a potent and specific angiotensin II (Ang II)-forming enzyme in vitro.
      There is also strong evidence to suggest its importance in vivo. Recent clinical
      studies have suggested that high serum cholesterol levels are associated with
      increased vascular chymase activity and this may assist in the development of
      atherosclerosis. This clinical finding has been reproduced in hamster models.
      Studies with transgenic mice overexpressing the human chymase gene suggest a
      direct association between vascular chymase upregulation and atherogenesis. There
      is also increased chymase activity following various cardiac diseases such as
      myocardial ischaemia, volume overload cardiac failure, cardiomyopathy and viral
      myocarditis, suggesting that increased cardiac chymase activity appears to be
      involved in cardiac remodelling.

PMID- 17199220
TI  - Rationale for angiotensin II receptor blocker therapy in chronic heart failure.
AB  - Inhibiting the synthesis of angiotensin II (Ang II) by angiotensin-converting
      enzyme (ACE) inhibitor treatment has long been established as the recommended
      therapy for heart failure (HF). As ACE inhibitors are only partially effective in
      blocking the formation of Ang II, additional treatment with selective Ang II
      receptor blockers (ARBs) promise additional benefits in patients with HF. This
      hypothesis is currently being evaluated in Val-HeFT, a large-scale, randomised,
      double-blind, placebo-controlled study on the effects of adding the highly
      selective ARB valsartan to usual therapy (diuretics, digoxin, beta-blockers, ACE
      inhibitors) for HF treatment.

PMID- 17199221
TI  - Will more complete inhibition of the RAAS with angiotensin receptor blockade
      improve survival following myocardial infarction?
AB  - Angiotensin-converting enzyme (ACE) inhibitors have a well-established role in
      the management of patients with hypertension, diabetes, heart failure and
      myocardial infarction (MI). ACE inhibitors have been particularly well studied in
      acute and chronic MI with consistent and substantial survival benefits
      demonstrated, particularly in the higher risk groups. The recent development of
      angiotensin II (Ang II) receptor blockers (ARBs) as a well tolerated
      pharmacological therapy to more completely inhibit the actions of Ang II at the
      AT1-receptor level raises questions concerning comparative efficacy with the
      proven ACE inhibitor experience. Two major trials will provide a direct
      comparison of ARBs with an ACE inhibitor. The Valsartan in Acute Myocardial
      Infarction (VALIANT) trial is specifically designed to compare and contrast the
      ARB, valsartan, used both alone as well as in combination with a proven ACE
      inhibitor regimen, in a high risk MI population. VALIANT, with its three arms
      targetting 14,500 patients, is uniquely poised to determine whether the
      pharmacological advance in the development of ARBs confers additional clinical
      (survival) value in high risk MI patients.

PMID- 17199222
TI  - [Characteristics of chronic neuropathic pain and their relationship with
      psychological well-being in spinal cord injury patients].
AB  - AIMS: To determine the prevalence of neuropathic pain (NP) in a sample of
      patients with spinal cord injury (SCI), to examine the relation between clinical,
      demographic and psychological characteristics with the prevalence of NP after SCI
      and the different types of NP, and to study predictive factors. PATIENTS AND
      METHODS: Transversal observational study of 260 patients who attended their
      annual revision. Main outcome measures included presence/absence of NP,
      psychological well-being index, detailed pain history and 0-10 numerical rating
      scale of average pain intensity. RESULTS: 93 patients (36%) with SCI had NP. Of
      the patients with NP, 35% showed pain at level, while 65% showed NP below the
      level of injury. The only variable with a predictive value on the prevalence of
      NP was older age at the time of SCI. Statistically significant differences were
      observed between the prevalence of NP and the perception of psychological well
      being; patients with NP were the ones with more psychological distress. As for
      the different types of NP, the variables with predictive value on the
      classification of NP were early onset of pain at level, and incompleteness of the
      lesion in the below level NP. CONCLUSION: The results of this study show that NP
      appears frequently after SCI being more prevalent in patients who suffered the
      injury at more advanced ages. NP has a negative impact on the perception of
      psychological well-being.

PMID- 17199223
TI  - [Estimation of the prevalence of attention deficit hyperactivity disorder among
      the standard population on the island of Majorca].
AB  - AIM: To determine the rate of prevalence of attention-deficit/ hyperactivity
      disorder (ADHD) in children of school age (6-11 years) in the Island of Mallorca.
      SUBJECTS AND METHODS: The epidemiological study was conducted using a community
      sample extracted by means of multi-stage stratified sampling according to areas
      (rural, city and touristy) and schooling (public, private and concerted) and
      consisted in 1,509 children of both sexes. The ADHD Rating Scales-IV (ADHD RS-IV)
      for home and school setting were used to collect data. The optimal approach to do
      a diagnostic evaluation, according with the literature, was using a cut-off point
      of 90 centil. RESULTS: The estimated prevalence of ADHD was 4.57% (CI at 99%: 3.0
      5.8%) and we also obtained 1.26% for the hyperactive subtype, 1.06% for the
      disattentional subtype, and 2.25% for the combined subtype. Contrary to what was
      expected, prevalence was higher for females but no statistically significant.
      There were no statistically significant differences between levels, schools or
      areas. CONCLUSIONS: The estimates for prevalence found in this study are
      consistent with those reported in the literature (between 3-5%). Using the ADHD
      rating scale which has different cut-off point regarding age, sex and setting and
      the fact that it was a poblational based study could explain the higher
      prevalence in the females. We propose a normalization of the scales in our area
      in other to confirm our findings.

PMID- 17199224
TI  - [Frequency of the IVS4+66A-G polymorphism in the alpha-synuclein gene in patients
      with Parkinson's disease in north-western Mexico].
AB  - INTRODUCTION: Parkinson disease (PD) is the second most common neurodegenerative
      disease of adult onset. Is a progressive movement disorder including tremor,
      bradykinesia, rigidity and postural instability, with an age onset between 43 and
      66 years. Histopathologically, is characterized by a severe loss of dopaminergic
      neurons in the substantia nigra and inclusions consisting of insoluble protein
      aggregates called Lewy bodies, this are comprised in part of alpha-synuclein. The
      etiology of PD is still not fully understood, but genetic analyses, epidemiologic
      studies and experimental models of PD are providing important new insights into
      the pathogenesis of PD. AIM: To determine allelic and genotypic frequencies of
      polymorphism IVS4+66A-G in the alpha-synuclein gene and to demonstrate its
      association with PD in northwest Mexican population. SUBJECTS AND METHODS:
      Genomic desoxyribonucleic acid (DNA) from 51 PD patients and 121 persons without
      PD were achieved by polymerase chain reaction and analyzed the allelic and
      genotypic distribution in IVS4+66A-G polymorphism of alpha-synuclein gene.
      RESULTS: The genotypic frequency of IVS4+66AA was 43.1% in PD patients and 38.8%
      in control group; IVS4+66GG was 2% in PD patients and 4.1% in control group,
      whereas 54.9% in PD patients and 57.1% in control group were heterozygous.
      Statistical differences were not observed between groups (p<0.05). CONCLUSIONS:
      Association was not observed between the IVS4+66A-G polymorphism and PD.

PMID- 17199225
TI  - [Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      (MELAS) with the A3243G mutation of the tRNALeu(UUR) gene of mtDNA in native
      American haplogroup B2].
AB  - INTRODUCTION: Mitochondrial encephalopathy, lactic acidosis and cerebrovascular
      accident syndrome (MELAS) is, from the clinical point of view, one of the best
      studied mitochondrial multisystemic disorders. This disease has mainly been
      associated to the mitochondrial desoxyribonucleic acid (mtDNA) mutation A3243G
      located in the tRNALeu(UUR) gene. Although a relation between European
      haplogroups and the presence of the 3243 mutation has not been described, nothing
      is known about the presence of this mutation in native American haplogroups. CASE
      REPORT: A 12 year-old female Mexican patient diagnosed with MELAS is reported.
      Besides neurological, biochemical and cytological examination, we also analyzed
      the particular mtDNA mutations related to MELAS and the whole genome was
      sequenced to determine the mitochondrial haplogroup. The A3243G mutation was
      detected in the patient and maternal relatives (mother and siblings, all of them
      asymptomatic). The genotype corresponds to the native American haplogroup B2 and
      contains two private non-synonymous polymorfisms. CONCLUSION: All the members of
      the family studied present different percentage of the A3243G mutation, being the
      patient who presented the highest value. The mtDNA genotype corresponds to the
      native American haplogroup B2 and the private polymorphisms do not confer any
      phenotypic modification in MELAS syndrome.

PMID- 17199226
TI  - [The dopaminergic system and addictions].
AB  - AIM: All psychoactive substances with a high abuse potential are characterized by
      altering the mesocorticolimbic dopaminergic neurotransmission system. In this
      article it is proposed to review the neurobiological mechanisms that comprise the
      foundation of the development of addiction. DEVELOPMENT: The acute drug intake
      provokes an increase in extracellular dopamine which, in vulnerable individuals,
      could be the start of the addictive process. Chronic drug use is accompanied by a
      reduction in the dopaminergic function with the development of neuroadaptive
      changes in the mesolimbic and mesocortical pathways. In the prefrontal cortex,
      the changes in dopaminergic function produce an inbalance between receptors D1
      and D2, which leads to a predominance of inhibitatory function. Dopaminergic
      innervation in the amygdala and its interaction with the nucleus accumbens plays
      an essential role in the conditioning of environmental stimuli, and can trigger
      the craving and relapse. In drug dependent patients, dopaminergic changes extend
      from the limbic regions to the associative and sensorimotor striatum, and affect
      the cortico-striatico-cortical circuits. CONCLUSION: The involvement of the
      dopaminergic systems is crucial in the development of addiction, from the early
      phases in which drug use begins as an object-directed instrumental behavior, to
      the consolidation of the addiction as a compulsive habit, controlled by stimulus
      response mechanisms, which progressively invade all aspects of the life of an
      individual.

PMID- 17199227
TI  - [Biomedical publications in Spain on debate (I): state of neurological journals].
AB  - INTRODUCTION: Bibliometric studies belong to the so-called 'social studies of
      science', and science policy constitutes one of its main applied fields,
      providing objective and useful tools for evaluating the results of scientific
      activity. Neurological sciences are very important in the bibliometric map of
      Spain about biomedicine and health sciences, from a quantitative (second thematic
      area in productivity, only after biology-biochemical) and a qualitative (high
      health costs and morbimortality) point of view. DEVELOPMENT: In Spain we can
      found about 360 biomedical journals, 18 of them related to the area of
      neurological sciences. In 2005, only 17 biomedical Spanish journals were in the
      Science Citation Index database, three of them in the field of neurosciences:
      Neurologia (impact factor = 0.57), Revista de Neurologia (0.39) and Neurocirugia
      (0.23), and these journals have also very good Latindex criteria about formal
      aspects. But it is important to mention that the impact factor specifically
      measures visibility and diffusion of the works published by these journals rather
      than their scientific quality. We search the answer to some questions about the
      present and future of biomedical journals in general and neurological journals in
      particular: paper or electronic publication?, free access or open access?,
      scientific journal or scientific article?, English or Spanish publication?
      CONCLUSIONS: The Acuerdo de Buenos Aires is an initiative to promote scientific
      neurological papers of high quality in Spanish. The current status of
      neurological journals in the bibliometric context of our country is good and open
      to the advantages of electronic and free access.

PMID- 17199229
TI  - [XLIV National Meeting on Clinical Neurophysiology (I)].

PMID- 17199228
TI  - [Sacred psychoactive seeds and ritual sacrifices in the Moche culture].
AB  - INTRODUCTION: Archaeological findings have confirmed the existence of
      representations of ritual human sacrifices on pottery belonging to the Moche
      culture (100-750 AD) in northern Peru; until recently these images were thought
      to be mythological narrations. We review the archaeological and ethno-historical
      data concerning Moche sacrifices and we attempt to identify the psychoactive
      seeds and plants used during such rites. DEVELOPMENT: Ethno-historical data from
      different chronicles of the New World written in the 16th century state that
      hamala seeds (belonging to the species Nectandra) were used for their analgesic,
      sedative, narcotic and anticoagulating properties, and that chamico, or
      stramonium, had an intoxicating effect on those who took it. There were two kinds
      of Moche rituals, that is, sacrifices as offerings to divinities and as exemplary
      punishments. Methods of sacrifice included slitting victims' throats,
      dismembering them and throwing them off mountains. The sacrifices of the Moche
      were part of a complex and elaborate ritual which consisted in capturing
      prisoners, parading them with nooses around their necks, making offerings,
      preparing the officiants and the community, consummation of the sacrifice and
      presenting the blood to the priest in a chalice. Human sacrifices were part of
      the propitiatory ceremonies held in honour of the gods in order to favour human
      fertility, obtain good harvests and preserve a plentiful supply of water for
      irrigating the valleys. CONCLUSIONS: The therapeutic properties of the seeds of
      the Nectandra species favoured their utilisation in the ritual sacrifices of the
      Moche culture. Their use was probably associated with stramonium and San Pedro
      cactus, which contain extracts rich in hallucinogenic alkaloids.

PMID- 17199230
TI  - [Neurosarcoidosis associated to hepatitis C that was not treated with
      interferon].

PMID- 17199231
TI  - [Topiramate in the treatment of epilepsy and a weight loss of 24 kg].

PMID- 17199232
TI  - [Movement disorders in Hashimoto's encephalopathy].

PMID- 17199233
TI  - Demand for private health insurance in Chinese urban areas.
AB  - Between 1993 and 2003, the proportion of urban residents without health insurance
      rose from 27 to 50%. The probability of outpatient visits in the previous 2 weeks
      dropped from 19.9 to 11.8% in urban areas between 1993 and 2003, and from 16.0 to
      13.9% in rural areas. To improve risk-pooling and risk-sharing, private health
      insurance should play an important role in China's health insurance system. This
      paper estimates the demand for private health insurance in urban areas using
      contingent valuation methods. Individuals were asked about their willingness-to
      pay (WTP) for major catastrophic disease insurance (MCDI), inpatient expenses
      insurance (IEI), and outpatient expenses insurance (OEI). The study was based on
      a household survey conducted in four small cities in China in 2004 and included
      2671 respondents. More people would like to buy IEI and MCDI (48.5 and 43.0%,
      respectively) than OEI (24.5%). In addition, individuals would pay a higher
      premium for MCDI and IEI than for OEI. The price elasticities of demand for MCDI,
      IEI, and OEI were -0.27, -0.34, and -0.42, respectively. The determinants of
      enrollment in the three private health insurance programs were similar with
      employment status, age, education, and income.

PMID- 17199234
TI  - Overview of on-farm bioremediation systems to reduce the occurrence of point
      source contamination.
AB  - Contamination of ground and surface water puts pressure on the use of pesticides.
      Pesticide contamination of water can often be linked to point sources rather than
      to diffuse sources. Examples of such point sources are areas on farms where
      pesticides are handled and filled into sprayers, and where sprayers are cleaned.
      To reduce contamination from these point sources, different kinds of
      bioremediation system are being researched in various member states of the EU.
      Bioremediation is the use of living organisms, primarily microorganisms, to
      degrade the environmental contaminants into less toxic forms. The systems
      available for biocleaning of pesticides vary according to their shape and design.
      Up till now, three systems have been extensively described and reported: the
      biobed, the Phytobac and the biofilter. Most of these constructions are
      excavations or different sizes of container filled with biological material.
      Typical overall clean-up efficiency exceeds 95%, realising even more than 99% in
      many cases. This paper provides an overview of the state of the art of these
      bioremediation systems and discusses their construction, efficiency and
      drawbacks.

PMID- 17199235
TI  - Efficacy and safety of donepezil over 3 years: an open-label, multicentre study
      in patients with Alzheimer's disease.
AB  - OBJECTIVE: This 132-week, open-label extension study assessed the long-term
      efficacy and safety of donepezil in 579 patients with mild to moderate
      Alzheimer's disease (AD) who had previously participated in a 24-week double
      blind study of 5 or 10 mg/day donepezil vs placebo. METHOD: Patients enrolled in
      the present study had a 6-week single-blind placebo washout period followed by
      treatment with donepezil 5 mg/day for 6 weeks with an optional increase in dosage
      to 10 mg/day between weeks 6 and 32. RESULTS: After 6 weeks of open-label
      treatment with donepezil 5 mg/day, mean Alzheimer's Disease Assessment Scale --
      cognitive subscale scores (ADAS-cog) improved by approximately two points, while
      after 12 weeks of open-label treatment (with a majority of patients receiving 10
      mg/day), the mean ADAS-cog score was 1 point better than the score at the end of
      the placebo washout period. Scores then declined gradually over the remainder of
      the study. Mean changes in Clinical Dementia Rating-Sum of Boxes scores showed
      slight improvement over the first 12 weeks of open-label treatment and then
      slowly declined for the remainder of the study period. Donepezil was well
      tolerated over the entire 162-week study period. Overall, 85% of patients
      experienced at least one adverse event (AE). The most common included diarrhoea
      (12%), nausea (11%), infection (11%) and accidental injury (10%). Some patients
      discontinued the study due to AEs (15%). CONCLUSIONS: These results support the
      conclusion that donepezil is safe and effective for the long-term treatment of
      patients with mild to moderate AD.

PMID- 17199236
TI  - Construction and validation of a patient- and user-friendly nursing home version
      of the Geriatric Depression Scale.
AB  - OBJECTIVE: To construct a patient- and user-friendly shortened version of the
      Geriatric Depression Scale (GDS) that is especially suitable for nursing home
      patients. METHODS: The study was carried out on two different data bases
      including 23 Dutch nursing homes. Data on the GDS (n = 410), the Mini Mental
      State Examination (n = 410) and a diagnostic interview (SCAN; n = 333), were
      collected by trained clinicians. Firstly, the items of the GDS-15 were judged on
      their clinical applicability by three clinical experts. Subsequently, items that
      were identified as unsuitable were removed using the data of the Assess project
      (n = 77), and internal consistency was calculated. Secondly, with respect to
      criterion validity (sensitivity, specitivity, area under ROC and positive and
      negative predictive values), the newly constructed shortened GDS was validated in
      the AGED data set (n = 333), using DSM-IV diagnosis for depression as measured by
      the SCAN as 'gold standard'. RESULTS: The eight-item GDS that resulted from stage
      1 showed good internal consistency in both the Assess data set (alpha = 0.86) and
      the AGED dataset (alpha = 0.80). In the AGED dataset, high sensitivity rates of
      96.3% for major depression and 83.0% for minor depression were found, with a
      specificity rate of 71.7% at a cut-off point of 2/3. CONCLUSION: The GDS-8 has
      good psychometric properties. Given that the GDS-8 is less burdening for the
      patient, more comfortable to use and less time consuming, it may be a more
      feasible screening test for the frail nursing home population.

PMID- 17199237
TI  - Dissatisfaction with performance of valued activities predicts depression in age
      related macular degeneration.
AB  - OBJECTIVE: To determine whether dissatisfaction with performance of valued
      activities predicts depression in patients with age-related macular degeneration
      (AMD). PATIENTS: Two hundred and six patients with newly diagnosed neovascular
      AMD in one eye and pre-existing AMD in the fellow eye who were participating in a
      clinical trial of a psychosocial intervention to prevent depression. MEASURES:
      Structured clinical evaluations of vision function, depression, visual acuity,
      contrast sensitivity and medical morbidity. Subjects were classified as
      dissatisfied if they indicated that they were dissatisfied with their performance
      of a valued activity. RESULTS: Subjects who were dissatisfied with performance of
      valued activities (n = 71) had similar demographic characteristics to satisfied
      subjects (n = 135) but had worse visual acuity (p < 0.054), greater medical
      comorbidity (p < 0.006), and lower vision function (p < 0.001). Dissatisfied
      subjects were almost 2.5 times more likely (OR = 2.41; [95% CI 1.02, 5.65]; p =
      0.044) to become depressed within 2 months than satisfied subjects independent of
      baseline visual acuity, vision function, and medical comorbidity. CONCLUSION:
      Dissatisfaction with performance of valued activities in older persons with AMD
      predicts depression over a 2-month period. Assessing the ability to pursue valued
      activities may identify patients at risk for depression and prompt clinicians to
      initiate rehabilitative interventions and careful surveillance for depression.

PMID- 17199238
TI  - Pharmaceutical and therapeutic potentials of essential oils and their individual
      volatile constituents: a review.
AB  - Essential oils and their volatile constituents are used widely to prevent and
      treat human disease. The possible role and mode of action of these natural
      products is discussed with regard to the prevention and treatment of cancer,
      cardiovascular diseases including atherosclerosis and thrombosis, as well as
      their bioactivity as antibacterial, antiviral, antioxidants and antidiabetic
      agents. Their application as natural skin penetration enhancers for transdermal
      drug delivery and the therapeutic properties of essential oils in aroma and
      massage therapy will also be outlined.

PMID- 17199239
TI  - The Chinese herbal preparation Qing Yi Tang (QYT) improves intestinal
      myoelectrical activity and increases intestinal transit during acute pancreatitis
      in rodents.
AB  - The aim was to investigate alterations of intestinal motility in models of acute
      pancreatitis and to investigate the effects of the Chinese herbal preparation
      Qing Yi Tang (QYT) on these alterations. Upper gastrointestinal transit was
      evaluated in mice following induction of mild acute pancreatitis (MAP) using
      caerulein. Myoelectrical activity was recorded in rats after induction of severe
      acute pancreatitis (SAP) using sodium deoxycholate (SDOC). The contractility of
      jejunum segments was evaluated in the presence of SDOC, lipopolysaccharide (LPS)
      and trypsin. QYT accelerated the transit in MAP mice in a concentration dependent
      manner. Slow wave activity of smooth muscle in rat stomach and jejunum remained
      unchanged following SAP, but the spiking activity was significantly decreased,
      with bursts of 7.2 +/- 2.6/10 min compared with 47.9 +/- 13.2/10 min without SAP
      (p < 0.01). QYT reversed this decrease. Additionally, the amplitudes of slow
      waves and spikes were enhanced by QYT in SAP rats. The tension and amplitude of
      spontaneous contractile activity was reduced by SDOC and LPS and increased by
      trypsin. Gastrointestinal (GI) transit is altered by SAP but not by MAP. The
      Chinese herbal preparation QYT improves disturbed motility in AP by stimulating
      myoelectrical activity and accelerating GI transit.

PMID- 17199240
TI  - Effect of insulin and its combination with resveratrol or curcumin in attenuation
      of diabetic neuropathic pain: participation of nitric oxide and TNF-alpha.
AB  - Diabetic neuropathic pain, an important microvascular complication in diabetes
      mellitus, is recognized as one of the most difficult types of pain to treat. The
      underlying mechanisms of painful symptoms may be closely associated with
      hyperglycaemia but a lack of the understanding of its proper aetiology,
      inadequate relief, development of tolerance and potential toxicity of classical
      antinociceptives warrant the investigation of newer agents to relieve this pain.
      The aim of the present study was to explore the antinociceptive effect of insulin
      and its combinations with resveratrol and curcumin in attenuating diabetic
      neuropathic pain. The study also aimed to examine the effect of these
      combinations on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO)
      levels in streptozotocin (STZ) induced diabetic mice. Four weeks after a single
      intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the
      tail immersion and hot-plate assays. Diabetic mice exhibited significant
      hyperalgesia along with increased plasma glucose and decreased body weights
      compared with control mice. Chronic treatment with insulin (10 IU/kg/day, s.c.)
      and its combinations with antioxidants (resveratrol 20 mg/kg or curcumin 60
      mg/kg, p.o.) for 4 weeks starting from the 4th week of STZ injection
      significantly attenuated thermal hyperalgesia and the hot-plate latencies. There
      was a significant inhibition of TNF-alpha and NO levels when these drugs were
      given in combination compared with their effects per se. These results indicate
      an antinociceptive activity of resveratrol and curcumin and point towards the
      beneficial effect of these combinations with insulin in attenuating diabetic
      neuropathic pain, possibly through the participation of NO and TNF-alpha.

PMID- 17199241
TI  - Monodisperse carbon-polymer mesoporous spheres with magnetic functionality and
      adjustable pore-size distribution.

PMID- 17199242
TI  - Can furfuryl alcohol generate single-crystalline nanostructures by thermal
      polymerization?

PMID- 17199243
TI  - Patterned polymer brushes grafted from bromine-functionalized, chemically active
      surface templates.

PMID- 17199245
TI  - Metal/Conducting-polymer composite nanowires.

PMID- 17199244
TI  - Fully depleted nanowire field-effect transistor in inversion mode.

PMID- 17199246
TI  - High electron mobility InAs nanowire field-effect transistors.
AB  - Single-crystal InAs nanowires (NWs) are synthesized using metal-organic chemical
      vapor deposition (MOCVD) and fabricated into NW field-effect transistors (NWFETs)
      on a SiO(2)/n(+)-Si substrate with a global n(+)-Si back-gate and sputtered
      SiO(x)/Au underlap top-gate. For top-gate NWFETs, we have developed a model that
      allows accurate estimation of characteristic NW parameters, including carrier
      field-effect mobility and carrier concentration by taking into account series and
      leakage resistances, interface state capacitance, and top-gate geometry. Both the
      back-gate and the top-gate NWFETs exhibit room-temperature field-effect mobility
      as high as 6580 cm(2) V(-1) s(-1), which is the lower-bound value without
      interface-capacitance correction, and is the highest mobility reported to date in
      any semiconductor NW.

PMID- 17199247
TI  - Fabrication of gold nanowires by electric-field-induced scanning probe
      lithography and in situ chemical development.

PMID- 17199248
TI  - Gold-silica-gold nanosandwiches: tunable bimodal plasmonic resonators.

PMID- 17199249
TI  - Crystallization of indium tin oxide nanoparticles: from cooperative behavior to
      individuality.
AB  - The crystallization pathway of indium tin oxide nanoparticles during solvothermal
      synthesis in benzyl alcohol was investigated. The synthesis was stopped after
      different reaction times in the range of 1-24 h, and the structural and
      morphological characteristics of the products were analyzed by powder X-ray
      diffraction, electron microscopy, and UV/Vis spectroscopy. Interestingly, the
      crystallization mechanism does not proceed along a simple nucleation and growth
      pathway, but involves a two-step process. In the first 12 h an intermediate phase
      is formed, which consists of nanocrystallites 3-6 nm in size stabilized by an
      organic matrix. In this organic-inorganic network the nanoparticles are aligned
      into superstructures, but without any crystallographic orientation. After 12 h
      the intermediate phase is abruptly transformed into indium tin oxide
      nanoparticles with the bixbyite structure and with crystallite sizes of about 10
      12 nm. This step is accompanied by the disappearance of the organic phase and the
      loss of the superstructure.

PMID- 17199250
TI  - Shell-by-shell synthesis of tin oxide hollow colloids with nanoarchitectured
      walls: cavity size tuning and functionalization.

PMID- 17199251
TI  - Colloidal synthesis of NixPt1-x nanoparticles with tuneable composition and size.

PMID- 17199253
TI  - Current literature in mass spectrometry.

PMID- 17199254
TI  - Visible-laser desorption/ionization on gold nanostructures.
AB  - In this report, we describe the visible-laser desorption/ionization of
      biomolecules deposited on gold-coated porous silicon and gold nanorod arrays. The
      porous silicon made by electrochemical etching was coated with gold using argon
      ion sputtering. The gold nanorod arrays were fabricated by electrodepositing gold
      onto a porous alumina template, and the subsequent partial removal of the alumina
      template. A frequency-doubled/tripled Nd : YAG laser was used to irradiate the
      gold nanostructured substrate, and the desorbed molecular ions were mass-analyzed
      by a time-of-flight mass spectrometer. The desorption/ionization of biomolecules
      for both substrates was favored by the use of the 532-nm visible-laser, which is
      in the range of the localized surface plasmon resonance of the gold
      nanostructure. The present technique offers a potential analytical method for low
      molecular-weight analytes that are rather difficult to handle in the conventional
      matrix-assisted laser desorption/ionization (MALDI) mass spectrometry.

PMID- 17199255
TI  - Mass spectrometric characterization of 3'-imino[60]fulleryl-3'-deoxythymidine by
      collision-induced dissociation.
AB  - The primary structure of 3'-imino[60]fulleryl-3'-deoxythymidine ions is studied
      using mass spectrometry both in the positive and negative modes. Interaction
      between the subunits is discussed using collision-induced dissociation (CID)
      spectra. Collisional activation with argon of the sodiated cations leads to the
      cleavage of the glycosidic bond and the transfer of a radical hydrogen from the
      deoxyribose to the thymine. The sodiated thymine is the only fragment observed
      for low collision energies in the positive mode. In the negative mode, two
      different ionization mechanisms take place, reduction and deprotonation in the
      presence of triethylamine. The 2.7 eV electron affinity of C60 and its huge cross
      section compared to the small cross section and predicted 0.44 eV electron
      affinity of the thymidine subunit most likely localize the radical electron on
      the fullerene. On the other hand, deprotonation of the 3'-azido-3'-deoxythymidine
      (AZT) is known to occur in N-3, the most acidic site of the nucleobase.
      Consequently, deprotonation causes the negative charge to be initially localized
      on the thymine. Both types of parent anions give the radical anion C60*- as
      fragment. The other fragments detected are the dehydrogenated 3'
      imino[60]fulleryl-3'-deoxyribose anion, C60NH2-, C60N- and C60H-. Since in
      negative ion mass spectrometry all fragments include the [60]fullerene unit, this
      suggests that the fragmentation is driven by the electron affinity of the
      [60]fullerene, likely responsible for a charge transfer between the deprotonated
      thymine and the C60.

PMID- 17199256
TI  - Analysis of sodium adduct paeoniflorin, albiflorin and their derivatives by
      (+)ESI-MSn, DFT calculations and computer-aided mass spectrometry analysis
      program.
AB  - In order to analyze paeoniflorin, albiflorin and their derivatives (PADs) in
      Paeonia Lactiflora rapidly and effectively, (+)ESI-MS(n) experiments were
      conducted, from which two diagnostic fragment patterns were acquired. Meanwhile,
      the dehydration ability of aglycones of PADs was obtained by calculating their
      activation energy using density functional theory, through which the unique
      dehydration phenomenon of benzoylalbiflorin, compared with benzoylpaeoniflorin,
      was interpreted. In addition, a computer-aided mass spectrometry analysis program
      was developed to facilitate the analysis of the unknown compound by suggesting
      the possible structure of the analyte.

PMID- 17199258
TI  - Isolation of Borrelia afzelii from overwintering Culex pipiens biotype molestus
      mosquitoes.
AB  - A total of 662 samples (winter period: 469; summer period: 193 specimens) of
      female mosquitoes of the genus Culex, Aedes and Anopheles were collected during
      the period March 2000-April 2001 from the locality of Vysoke Myto (Eastern
      Bohemia, Czech Republic). They were examined by dark field microscopy for the
      presence of spirochetes. The motile spirochetes were observed in 4.2 % of all
      species of investigated mosquitoes. One spirochetal strain out of the 8 isolation
      attempts (BRZ14) was obtained (cultivation rate was 12.5 %) and the spirochetal
      strain was then successfully cultivated and identified using PCR for the presence
      of Borrelia burgdorferi s.l., and subsequently with the RFLP as genomospecies
      Borrelia afzelii. This strain was derived from overwintering Culex (Culex)
      pipiens biotype molestus female mosquitoe. This is apparently one of the sporadic
      cases of the occurrence of pathogenic borreliae in haematophagous arthropods,
      other than Ixodes ricinus complex ticks.

PMID- 17199257
TI  - Phospholipid and triacylglycerol fatty acid content and pattern in the cardiac
      endothelium of rats depleted in long-chain polyunsaturated omega 3 fatty acids.
AB  - Rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3-depleted
      rats) display several features of the metabolic syndrome including hypertension
      and cardiac hypertrophy. This coincides with alteration of the cardiac muscle
      phospholipid and triacylglycerol fatty acid content and/or pattern. In the
      present study, the latter variables were measured in the cardiac endothelium of
      normal and omega3-depleted rats. Samples derived from four rats each were
      obtained from 16 female normal fed rats and three groups of 36-40 female fed
      omega3-depleted rats each aged 8-9, 15-16 and 22-23 weeks. At comparable mean
      age, the ratio between the square root of the total fatty acid content of
      phospholipids and cubic root of the total fatty acid content of triacylglycerols
      was lower in omega3-depleted rats than in control animals. The total fatty acid
      content of triacylglycerols was inversely related to their relative content in
      C20:4omega6. Other differences between omega3-depleted rats and control animals
      consisted in a lower content of long-chain polyunsaturated omega3 fatty acids in
      both phospholipids and triacylglycerols, higher content of long-chain
      polyunsaturated omega6 fatty acids in phospholipids, higher activity of delta9
      desaturase (C16:0/C16:1omega7 and C18:0/C18:1omega9 ratios) and elongase [(C16:0
      + C16:1omega7)/(C18:0 + C18:1omega9) and C20:4omega6/C22:4omega6 ratios], but
      impaired generation of C22:6omega3 from C22:5omega3 in the former rats. These
      findings support the view that cardiovascular perturbations previously documented
      in the omega3-depleted rats may involve impaired heart endothelial function.

PMID- 17199259
TI  - Regioselective arene hydroxylation mediated by a (mu-peroxo)diiron(III) complex:
      a functional model for toluene monooxygenase.

PMID- 17199260
TI  - Fe(I)-mediated reductive cleavage and coupling of CO(2): an Fe(II)(mu-O, mu
      CO)Fe(II) core.

PMID- 17199262
TI  - A single-molecule magnet with a "twist".

PMID- 17199261
TI  - Self-repair of thymine dimer in duplex DNA.

PMID- 17199263
TI  - Kinase-catalyzed biotinylation for phosphoprotein detection.

PMID- 17199264
TI  - Immobilizing au nanoparticles with polymer single crystals, patterning and
      asymmetric functionalization.

PMID- 17199265
TI  - Mammalian cell surface imaging with nitrile-functionalized nanoprobes:
      biophysical characterization of aggregation and polarization anisotropy in SERS
      imaging.

PMID- 17199266
TI  - A dynamic Zn site in Helicobacter pylori HypA: a potential mechanism for metal
      specific protein activity.

PMID- 17199267
TI  - Role of c,c'-linkage in the formation and stabilization of supercarboranes.
      Synthesis and structure of carbon-atoms-apart 13-vertex carborane and 14-vertex
      metallacarborane.

PMID- 17199268
TI  - Nanowindow-regulated specific capacitance of supercapacitor electrodes of single
      wall carbon nanohorns.

PMID- 17199269
TI  - Rh-catalyzed intermolecular reactions of alkynes with alpha-diazoesters that
      possess beta-hydrogens: ligand-based control over divergent pathways.

PMID- 17199271
TI  - An isolable disilyne anion radical and a new route to the disilenide ion upon
      reduction of a disilyne.

PMID- 17199270
TI  - Two-step potentially prebiotic synthesis of alpha-d-cytidine-5'-phosphate from d
      glyceraldehyde-3-phosphate.

PMID- 17199273
TI  - Why excess cyanide can be detrimental to Pd-catalyzed cyanation of haloarenes.
      Facile formation and characterization of [Pd(CN)(3)(H)](2-) and [Pd(CN)(3)(Ph)](2
      ).

PMID- 17199272
TI  - Regio- and chemoselective silylmetalation of functionalized terminal alkenes.

PMID- 17199274
TI  - Preparation and reactivity of nanocrystalline cocrystals formed via
      sonocrystallization.

PMID- 17199275
TI  - Synthesis and phase transformation of In(2)Se(3) and CuInSe(2) nanowires.

PMID- 17199276
TI  - Production of dihydroisocoumarins in Fusarium verticillioides by swapping
      ketosynthase domain of the fungal iterative polyketide synthase Fum1p with that
      of lovastatin diketide synthase.

PMID- 17199278
TI  - Shape selectivity in the assembly of lithographically designed colloidal
      particles.

PMID- 17199277
TI  - Mild reductive opening of aryl pyranosides promoted by scandium(III) triflate.

PMID- 17199279
TI  - Low temperature CO oxidation over unsupported nanoporous gold.
AB  - Supported Au nanoclusters are well-known for their unusual properties in
      catalysis. We describe here that nanostructured porous Au made via dealloying
      represents a new class of unsupported catalysts with extraordinary activities in
      important reactions such as CO oxidation. Although nanoporous Au may contain some
      oxides on the surface, our results demonstrate that it is metallic Au that plays
      the main role in this catalytic reaction. Furthermore, this material has good low
      temperature catalytic stability and is extremely CO tolerant.

PMID- 17199280
TI  - Direct N-cyclopropylation of cyclic amides and azoles employing a
      cyclopropylbismuth reagent.

PMID- 17199281
TI  - Methods to explore cellular uptake of ruthenium complexes.

PMID- 17199282
TI  - Structural criteria for the design of anion receptors: the interaction of halides
      with electron-deficient arenes.

PMID- 17199283
TI  - High fidelity functional patterns of an extracellular matrix protein by electron
      beam-based inactivation.
AB  - Controlling the organization of proteins on surfaces provides a powerful
      biochemical tool for determining how cells interpret the spatial distribution of
      local signaling molecules. Here, we describe a general high fidelity approach
      based on electron beam writing to pattern the functional properties of protein
      coated surfaces at length scales ranging from tens of nanometers to millimeters.
      A silicon substrate is first coated with the extracellular matrix protein
      fibronectin, which is then locally inactivated by exposure to a highly focused
      electron beam. Biochemical inactivation of the protein is established by the loss
      of antibody binding to the fibronectin. Functional inactivation is determined by
      the inability of cells to spread or form focal adhesions on the inactivated
      substrate, resulting in cell shapes constrained to the pattern, while they do
      both (and are unconstrained) on the remaining fibronectin. These protein patterns
      have very high fidelity, and typical patterns agree with the input dimensions of
      the pattern to within 2%. Further, the feature edges are well defined and
      approach molecular dimensions in roughness. Inactivation is shown to be dose
      dependent with observable suppression of the specific binding at 2 microC cm(-2)
      and complete removal of biochemical activity at approximately 50 microC cm(-2)
      for 5 keV electrons. The critical dose for inactivation also depends on
      accelerating voltage, and complete loss of antibody binding was achieved at
      approximately 4-7 microC cm(-2) for 1 keV electrons, which corresponds to
      approximately 50-90 electrons per cross-sectional area of a whole fibronectin
      dimer and ~2-4 electrons per type III fibronectin domain. AFM analysis of the
      pattern surfaces revealed that electron beam exposure does not remove appreciable
      amounts of material from the surface, suggesting that the patterning mechanism
      involves local inactivation rather than the ablation that has been observed in
      several organic thin film systems.

PMID- 17199285
TI  - Brilliant Sm, Eu, Tb, and Dy chiral lanthanide complexes with strong circularly
      polarized luminescence.
AB  - The synthesis, characterization, and luminescent behavior of trivalent Sm, Eu,
      Dy, and Tb complexes of two enantiomeric, octadentate, chiral, 2
      hydroxyisophthalamide ligands are reported. These complexes are highly
      luminescent in solution. Functionalization of the achiral parent ligand with a
      chiral 1-phenylethylamine substituent on the open face of the complex in close
      proximity to the metal center yields complexes with strong circularly polarized
      luminescence (CPL) activity. This appears to be the first example of a system
      utilizing the same ligand architecture to sensitize four different lanthanide
      cations and display CPL activity. The luminescence dissymmetry factor, g(lum),
      recorded for the Eu(III) complex is one of the highest values reported, and this
      is the first time the CPL effect has been demonstrated for a Sm(III) complex with
      a chiral ligand. The combination of high luminescence intensity with CPL activity
      should enable new bioanalytical applications of macromolecules in chiral
      environments.

PMID- 17199284
TI  - Highly diastereoselective synthesis of nucleoside adducts from the carcinogenic
      benzo[a]pyrene diol epoxide and a computational analysis.
AB  - A diastereoselective synthesis of the nucleoside adducts corresponding to a cis
      ring-opening of the carcinogen (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha
      epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP DE-2) by 2'-deoxyadenosine and 2'
      deoxyguanosine is described. The key intermediate (+/-)-10alpha-amino
      7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene was synthesized
      by a highly diastereoselective dihydroxylation wherein phenylboronic acid was a
      water surrogate. The resulting boronate ester was converted to a tetraol
      derivative in which two of the four hydroxyl groups (trans 7, 8) were protected
      as benzoate esters while the remaining two (cis 9, 10) were free. The cis glycol
      entity was then subjected to a reaction with 1-chlorocarbonyl-1
      methylethylacetate to yield an intermediate chloro monoacetoxy dibenzoate.
      Displacement of the halide with azide, complete cleavage of the esters, and
      catalytic reduction of the azide yielded the requisite amino triol. Fluoride
      displacement from appropriately protected nucleoside derivatives, 6-fluoropurine
      2'-deoxyribonucleoside and 2-fluoro-2'-deoxyinosine, by the amino triol then
      yielded diastereomeric pairs of diol epoxide-adducted 2'-deoxyadenosine (dA) and
      2'-deoxyguanosine (dG) nucleosides. Small aliquots of these adducts were
      separated for characterization purposes. The present approach provides the first
      diastereoselective synthesis of the cis adducts of BaP DE-2 with 2'
      deoxyguanosine as well as the first synthesis of both dA and dG adducts from a
      common intermediate. An informative analysis of the 1H NMR spectra of the cis
      adducts synthesized and comparisons to the trans adducts are reported. To gain
      insight into the diastereoselectivity in the key dihydroxylation step, a
      computational analysis, including molecular mechanics (MMFF94) and semiempirical
      AM1 geometry optimizations, yielded results that are in fairly good agreement
      with the experimental observations.

PMID- 17199286
TI  - Silica-stabilized gold island films for transmission localized surface plasmon
      sensing.
AB  - Ultrathin gold films prepared by evaporation of sub-percolation layers (typically
      up to 10 nm nominal thickness) onto transparent substrates form arrays of well
      defined metal islands. Such films display a characteristic surface plasmon (SP)
      absorption band, conveniently measured by transmission spectroscopy. The SP band
      intensity and position are sensitive to the film morphology (island shape and
      inter-island separation) and the effective dielectric constant of the surrounding
      medium. The latter has been exploited for chemical and biological sensing in the
      transmission localized surface plasmon resonance (T-LSPR) mode. A major concern
      in the development of T-LSPR sensors based on Au island films is instability,
      manifested as change in the SP absorbance following immersion in organic solvents
      and aqueous solutions. The latter may present a problem in the use of Au island
      based transducers for biological sensing, usually carried out in aqueous media.
      Here, we describe a facile method for stabilizing Au island films while
      maintaining a high sensitivity of the SP absorbance to analyte binding.
      Stabilization is achieved by coating the Au islands with an ultrathin silica
      layer, ca. 1.5 nm thick, deposited by a sol-gel procedure on an intermediate
      mercaptosilane monolayer. The silica coating is prepared using a modified
      literature procedure, where a change in the reaction conditions from room
      temperature to 90 degrees C shortened the deposition time from days to hours. The
      system was characterized by UV-vis spectroscopy, ellipsometry, XPS, HRSEM, AFM,
      and cyclic voltammetry. The ultrathin silica coating stabilizes the optical
      properties of the Au island films toward immersion in water, phosphate buffer
      saline (PBS), and various organic solvents, thus providing proper conditions
      where the optical response is sensitive only to changes in the effective
      dielectric constant of the immediate environment. The silica layer is thin enough
      to afford high T-LSPR sensitivity, while the hydroxyl groups on its surface
      enable chemical modification for binding of receptor molecules. The use of silica
      encapsulated Au island films as a stable and effective platform for T-LSPR
      sensing is demonstrated.

PMID- 17199287
TI  - High-yield activation of scaffold polymer surfaces to attach cell adhesion
      molecules.
AB  - Zirconium tetra(tert-butoxide) reacts with surface amide groups of polyamide
      nylon 6/6 to give (eta(2)-amidate)zirconium complexes in high yield. These
      surface complexes react to bond the cell-adhesive peptide arginine-glycine
      aspartic acid (RGD) to the polymer surface. A surface loading of 0.18 nmol/cm(2)
      of RGD is achieved, which is 20-1000 times higher than previously reported
      attainable on natural or synthetic polymers by other strategies. Approximately
      40% of the nylon surface is covered by the RGD, which gives a surface that is
      both stable to hydrolysis and highly active for cell adhesion and spreading in
      vitro.

PMID- 17199288
TI  - Composite particles of polyethylene @ silica.
AB  - Polyethylene (PE) and silica are perhaps the simplest and most common organic and
      inorganic polymers, respectively. We describe, for the first time, a physically
      interpenetrating nanocomposite between these two elementary polymers. While
      polymer-silica composites are well known, the nanometric physical blending of PE
      and silica has remained a challenge. A method for the preparation of such
      materials, which is based on the entrapment of dissolved PE in a polymerizing
      tetraethoxysilane (TEOS) system, has been developed. Specifically, the
      preparation of submicron particles of low-density PE@silica and high-density
      PE@silica is detailed, which is based on carrying out a silica sol-gel
      polycondensation process within emulsion droplets of TEOS dissolved PE, at
      elevated temperatures. The key to the successful preparation of this new
      composite has been the identification of a surfactant, PE-b-PEG, that is capable
      of stabilizing the emulsion and promoting the dissolution of the PE. A mechanism
      for the formation of the particles as well as their inner structure are proposed,
      based on a large battery of analyses, including transmission electron microscopy
      (TEM) and scanning electron microscopies (SEM), surface area and porosity
      analyses, various thermal analyses including thermal gravimetric analysis
      (TGA/DTA) and differential scanning calorimetry (DSC) measurements, small-angle X
      ray scattering (SAXS) measurements and solid-state NMR spectroscopy.

PMID- 17199289
TI  - Supramolecular control of unwinding and rewinding of a double helix of
      oligoresorcinol using cyclodextrin/adamantane system.
AB  - The double helix of the oligoresorcinol nonamer formed in water was unwound by
      beta-cyclodextrin (beta-CD), and the resulting single strands of the nonamer
      threaded the beta-CD to form a twisted [3]-pseudorotaxane with a controlled
      helicity. Upon the addition of an adamantane, the single strand of the
      oligoresorcinol nonamer was expelled out of the beta-CD wheels, thus regenerating
      the double helix. This supramolecularly controlled, reversible unwinding and
      rewinding of the double helix is unique and can be readily monitored by
      spectroscopic techniques.

PMID- 17199291
TI  - Formation of the early photoproduct lumi-R of cyanobacterial phytochrome cph1
      observed by ultrafast mid-infrared spectroscopy.
AB  - The photoreactions of the Pr ground state of cyanobacterial phytochrome Cph1 from
      Synechocystis PCC 6803 have been investigated by picosecond time-resolved mid
      infrared spectroscopy at ambient temperature. With femtosecond excitation of the
      Pr state at 640 nm, the photoisomerized Lumi-R product state is generated with
      kinetics and associated difference spectra indicative of vibrational cooling with
      tau(1) = 3 ps time constant and excited state decay with tau(1) = 3 ps, tau(2) =
      14 ps, and tau(3) = 134 ps time constants. The Lumi-R state is characterized by
      downshifted absorption of three C=C modes assigned to C(15)=C(16), C(4)=C(6), and
      a delocalized C=C mode, in addition to the downshifted C(19)=O mode. The Lumi-R
      minus Pr difference spectrum is indicative of global restructuring of the
      chromophore on the ultrafast timescale, which is discussed in light of C(15) Z/E
      photoisomerization in addition to changes near C(5), which could be low bond
      order torsional angle changes.

PMID- 17199290
TI  - Fe L-edge X-ray absorption spectroscopy of low-spin heme relative to non-heme Fe
      complexes: delocalization of Fe d-electrons into the porphyrin ligand.
AB  - Hemes (iron porphyrins) are involved in a range of functions in biology,
      including electron transfer, small-molecule binding and transport, and O2
      activation. The delocalization of the Fe d-electrons into the porphyrin ring and
      its effect on the redox chemistry and reactivity of these systems has been
      difficult to study by optical spectroscopies due to the dominant porphyrin pi-
      >pi(*) transitions, which obscure the metal center. Recently, we have developed a
      methodology that allows for the interpretation of the multiplet structure of Fe L
      edges in terms of differential orbital covalency (i.e., differences in mixing of
      the d-orbitals with ligand orbitals) using a valence bond configuration
      interaction (VBCI) model. Applied to low-spin heme systems, this methodology
      allows experimental determination of the delocalization of the Fe d-electrons
      into the porphyrin (P) ring in terms of both P-->Fe sigma and pi-donation and Fe-
      >P pi back-bonding. We find that pi-donation to Fe(III) is much larger than pi
      back-bonding from Fe(II), indicating that a hole superexchange pathway dominates
      electron transfer. The implications of the results are also discussed in terms of
      the differences between heme and non-heme oxygen activation chemistry.

PMID- 17199292
TI  - Catalyst-assisted solution-liquid-solid synthesis of CdS/CdSe nanorod
      heterostructures.
AB  - We report the synthesis and characterization of axial nanorod heterostructures
      composed of cadmium selenide (CdSe) and cadmium sulfide (CdS). The synthesis
      employs a solution-liquid-solid (SLS) mechanism with the assistance of bismuth
      nanocrystals adhered to a substrate (silicon or a III-V semiconductor).
      Transmission electron microscopy (TEM) and diffraction studies show that CdSe and
      CdS segments exhibit the wurtzite (hexagonal) crystal structure with <5% stacking
      faults. Both of these segments grow along the [002] direction with an epitaxial
      interface between them. Energy-dispersive X-ray (EDX) spectrometry using a high
      resolution TEM operating in scanning mode confirms the alloy-free composition
      modulation in the nanorod heterostructures, showing that Se and S are localized
      in the CdSe and CdS portions of the nanorod heterostructures, respectively. This
      study demonstrates that SLS synthesis provides an alternate route to prepare
      axial nanorod heterostructures that have been difficult to generate using either
      vapor-liquid-solid growth or catalyst-free solution-phase synthesis.

PMID- 17199293
TI  - (alpha/beta+alpha)-peptide antagonists of BH3 domain/Bcl-x(L) recognition: toward
      general strategies for foldamer-based inhibition of protein-protein interactions.
AB  - The development of molecules that bind to specific protein surface sites and
      inhibit protein-protein interactions is a fundamental challenge in molecular
      recognition. New strategies for approaching this challenge could have important
      long-term ramifications in biology and medicine. We are exploring the concept
      that unnatural oligomers with well-defined conformations ("foldamers") can mimic
      protein secondary structural elements and thereby block specific protein-protein
      interactions. Here, we describe the identification and analysis of helical
      peptide-based foldamers that bind to a specific cleft on the anti-apoptotic
      protein Bcl-xL by mimicking an alpha-helical BH3 domain. Initial studies,
      employing a fluorescence polarization (FP) competition assay, revealed that among
      several alpha/beta- and beta-peptide foldamer backbones only alpha/beta-peptides
      intended to adopt 14/15-helical secondary structure display significant binding
      to Bcl-xL. The most tightly binding Bcl-xL ligands are chimeric oligomers in
      which an N-terminal alpha/beta-peptide segment is fused to a C-terminal alpha
      peptide segment ((alpha/beta + alpha)-peptides)). Sequence-affinity relationships
      were probed via standard and nonstandard techniques (alanine scanning and
      hydrophile scanning, respectively), and the results allowed us to construct a
      computational model of the ligand/Bcl-xL complex. Analytical ultracentrifugation
      with a high-affinity (alpha/beta + alpha)-peptide established 1:1 ligand:Bcl-xL
      stoichiometry under FP assay conditions. Binding selectivity studies with the
      most potent (alpha/beta + alpha)-peptide, conducted via surface plasmon resonance
      measurements, revealed that this ligand binds tightly to Bcl-w as well as to Bcl
      xL, while binding to Bcl-2 is somewhat weaker. No binding could be detected with
      Mcl-1. We show that our most potent (alpha/beta + alpha)-peptide can induce
      cytochrome C release from mitochondria, an early step in apoptosis, in cell
      lysates, and that this activity is dependent upon inhibition of protein-protein
      interactions involving Bcl-xL.

PMID- 17199294
TI  - Charge recombination versus charge separation in donor-bridge-acceptor systems.
AB  - Optimizing the ratio of the rates for charge separation (CS) over charge
      recombination (CR) is crucial to create long-lived charge-separated states.
      Mastering the factors that govern the electron transfer (ET) rates is essential
      when trying to achieve molecular-scale electronics, artificial photosynthesis,
      and also for the further development of solar cells. Much work has been put into
      the question of how the donor-acceptor distances and donor-bridge energy gaps
      affect the electronic coupling, V(DA), and thus the rates of ET. We present here
      a unique comparison on how these factors differently influence the rates for CS
      and CR in a porphyrin-based donor-bridge-acceptor model system. Our system
      contains three series, each of which focuses on a separate charge-transfer rate
      determining factor, the donor-acceptor distance, the donor-bridge energy gap, and
      last, the influence of the electron acceptor on the rate for charge transfer. In
      these three series both CS and CR are governed by superexchange interactions
      which make a CR/CS comparative study ideal. We show here that the exponential
      distance dependence increases slightly for CR compared to that for CS as a result
      of the increased tunneling barrier height for this reaction, in accordance with
      the McConnell superexchange model. We also show that the dependence on the
      tunneling barrier height is different for CS and CR. This difference is highly
      dependent on the electron acceptor and thus cannot solely be explained by the
      differences in the frontier orbitals of the electron donor in these porphyrin
      systems.

PMID- 17199295
TI  - Tunneling in the 1,5-hydrogen shift reactions of 1,3-cyclopentadiene and 5-methyl
      1,3-cyclopentadiene.
AB  - MPW1K/6-31+G(d,p) calculations which include the effects of small curvature
      tunneling find that, around room temperature, thermally activated tunneling
      dominates the 1,5-hydrogen shift reactions of 1,3-cyclopentadiene (2a) and 5
      methyl-1,3-cyclopentadiene (2c). The calculated temperature dependence of the H/D
      kinetic isotope effect (KIE) for the latter rearrangement agrees well with
      experimental measurements that were published nearly 40 years ago. It is argued
      that the experimental KIEs provide prima facie evidence for tunneling in this
      reaction. The calculations also predict that it should be possible, at least in
      principle, to confirm this conclusion by observing curvature in the Arrhenius
      plot for the rearrangement of 2c.

PMID- 17199296
TI  - Characterization of folding intermediates of a domain-swapped protein by solid
      state NMR spectroscopy.
AB  - We have employed two-dimensional solid-state NMR to study structure and dynamics
      of insoluble folding states of the domain-swapped protein Crh. Starting from the
      protein precipitated at its pI, conformational changes due to a modest
      temperature increase were investigated at the level of individual residues and in
      real-time. As compared to the crystalline state, Crh pI-precipitates exhibited a
      higher degree of molecular mobility for several regions of the protein. A rigidly
      intact center was observed including a subset of residues of the hydrophobic
      core. Raising the temperature by 13 K to 282 K created a partially unfolded
      intermediate state that was converted into beta-sheet-rich aggregates that are
      mostly of spherical character according to electron microscopy. Residue-by
      residue analysis indicated that two out of three alpha-helices in aggregated Crh
      underwent major structural rearrangements while the third helix was preserved.
      Residues in the hinge region exhibited major chemical-shift changes, indicating
      that the domain swap was not conserved in the aggregated form. Our study provides
      direct evidence that protein aggregates of a domain-swapped protein retain a
      significant fraction of native secondary structure and demonstrates that solid
      state NMR can be used to directly monitor slow molecular folding events.

PMID- 17199297
TI  - Well-defined surface imido amido tantalum(v) species from ammonia and silica
      supported tantalum hydrides.
AB  - The MCM-41 supported hydrides [([triple bond]SiO)(2)TaH(3)], 1a, and [([triple
      bond]SiO)(2)TaH(3)], 1b, cleave N-H bonds of ammonia at room temperature to yield
      the well-defined imido amido surface complexes [([triple
      bond]SiO)(2)Ta(NH)(NH(2))], 2, and 2xNH(3). Additionally, the surface silanes
      [[triple bond]Si-H] that exist in close proximity to 1a and 1b also react with
      ammonia at room temperature to give the surface silylamido [Si-NH(2)]. Such
      reaction is tantalum assisted: surface silanes were synthesized independently and
      in absence of tantalum by reaction of highly strained silica, SiO(2-1000), with
      SiH(4) and no reaction with ammonia was observed. Surface-supported complexes 2,
      2xNH(3), and [[triple bond]Si-NH(2)] have been characterized by, inter alia,
      solid-state NMR, IR, and EXAFS and independent synthesis of [[triple bond]Si
      NH(2)]. The NMR studies on the fully 15N-labeled samples have led to unambiguous
      discrimination between imido, amido, and amino resonances of 2*, 2*x(15)NH(3),
      and [[triple bond]Si-15NH(2)] through the combination of solid-state magic angle
      spinning (MAS), heteronuclear correlation (HETCOR), 2D proton double-quantum (DQ)
      single-quantum (SQ) correlation, and 2D proton triple-quantum (TQ) single-quantum
      (SQ) correlation spectra. The in situ IR monitoring of the reaction of 1a and 1b
      with regular NH(3) and 15NH(3), and after H/D exchange has yielded the
      determination of all the NH(x) vibration and deformation modes, with their
      respective H/D and 14N/15N isotopic shifts. EXAFS study yielded the bond
      distances in 2 of 1.79(2) Angstrom for Ta=N, 1.89(1) Angstrom for Ta-O, and
      1.98(2) Angstrom for Ta-N.

PMID- 17199298
TI  - Proton-coupled electron transfer in soybean lipoxygenase: dynamical behavior and
      temperature dependence of kinetic isotope effects.
AB  - The dynamical behavior and the temperature dependence of the kinetic isotope
      effects (KIEs) are examined for the proton-coupled electron transfer reaction
      catalyzed by the enzyme soybean lipoxygenase. The calculations are based on a
      vibronically nonadiabatic formulation that includes the quantum mechanical
      effects of the active electrons and the transferring proton, as well as the
      motions of all atoms in the complete solvated enzyme system. The rate constant is
      represented by the time integral of a probability flux correlation function that
      depends on the vibronic coupling and on time correlation functions of the energy
      gap and the proton donor-acceptor mode, which can be calculated from classical
      molecular dynamics simulations of the entire system. The dynamical behavior of
      the probability flux correlation function is dominated by the equilibrium protein
      and solvent motions and is not significantly influenced by the proton donor
      acceptor motion. The magnitude of the overall rate is strongly influenced by the
      proton donor-acceptor frequency, the vibronic coupling, and the protein/solvent
      reorganization energy. The calculations reproduce the experimentally observed
      magnitude and temperature dependence of the KIE for the soybean lipoxygenase
      reaction without fitting any parameters directly to the experimental kinetic
      data. The temperature dependence of the KIE is determined predominantly by the
      proton donor-acceptor frequency and the distance dependence of the vibronic
      couplings for hydrogen and deuterium. The ratio of the overlaps of the hydrogen
      and deuterium vibrational wavefunctions strongly impacts the magnitude of the KIE
      but does not significantly influence its temperature dependence. For this enzyme
      reaction, the large magnitude of the KIE arises mainly from the dominance of
      tunneling between the ground vibronic states and the relatively large ratio of
      the overlaps between the corresponding hydrogen and deuterium vibrational
      wavefunctions. The weak temperature dependence of the KIE is due in part to the
      dominance of the local component of the proton donor-acceptor motion.

PMID- 17199299
TI  - Synthetic control over magnetic moment and exchange bias in all-oxide materials
      encapsulated within a spherical protein cage.
AB  - This work focuses on the synthetic control of magnetic properties of mixed oxide
      magnetic nanoparticles of the general formula Fe(3-x)Co(x)O(4) (x < or = 0.33) in
      the protein cage ferritin. In this biomimetic approach, variations in the
      chemical synthesis result in the formation of single-phase Fe(3-x)Co(x)O(4)
      alloys or intimately mixed binary phase Fe/Co oxides, modifying the chemical
      structure and magnetic behavior of these particles, as characterized by static
      and dynamic magnetization measurements and X-ray absorption spectroscopy.

PMID- 17199300
TI  - Unusual crystallization behaviors of anatase nanocrystallites from a molecularly
      thin titania nanosheet and its stacked forms: increase in nucleation temperature
      and oriented growth.
AB  - Crystallization behaviors of anatase nanocrystallites from an ultrathin two
      dimensional reactant composed of exfoliated titania nanosheets have been studied
      by monitoring the heating process of their well-organized films, with which the
      film thickness can be controlled from a molecularly thin monolayer to a stacked
      multilayer structure with a stepwise increment of approximately 1 nm. The heated
      products were identified by means of total reflection fluorescence X-ray
      absorption near-edge structure analysis and in-plane X-ray diffraction
      measurements using a synchrotron radiation source. The films composed of five or
      more layers of stacked nanosheets were transformed into anatase at 400-500
      degrees C, which is a normal crystallization temperature of anatase from bulk
      reactants. As the film became thinner by decreasing the number of nanosheet
      layers to five or less, the crystallization temperature was found to increase and
      finally reached 800 degrees C for the monolayer film. Interestingly, preferential
      growth of anatase along the c-axis was strongly promoted for these ultrathin
      films. These unusual behaviors may be understood in terms of crystallization from
      the two-dimensional system of scarcely distributed reactants. The titania
      nanosheet crystallite is much thinner than the unit cell dimensions of anatase,
      and therefore, extensive atomic diffusion is required for the transformation
      particularly for the ultrathin films with a critical number (2-3) of stacked
      nanosheet layers. There is some structural similarity between anatase and titania
      nanosheet, which may account for the oriented growth of anatase nanocrystallites.

PMID- 17199301
TI  - Controlling the helicity of 2,2'-bipyridyl ruthenium(II) and zinc(II) hemicage
      complexes.
AB  - Two enantiomers of a new 4,5-pineno-2,2'-bipyridine ligand were synthesized and
      subsequently incorporated into hemicage ligands through a phenyl linker to yield
      ligands (+)-L1 and (-)-L1 or through a mesityl linker to yield ligands (+)-L2 and
      (-)-L2. Complexation of these ligands to Ru(II) afforded diastereomerically pure
      Delta and Lambda isomers, as verified through circular dichroism and circularly
      polarized luminescence spectroscopy. Ligands (+)-L2 and (-)-L2 were further
      coordinated to Zn(II) to form a complex with intriguing photophysical properties.
      Whereas Zn(bpy)32+ was shown to be a fluorescent emitter outside the visible
      spectrum, the caging process provided an unprecedented enhancement of intersystem
      crossing and subsequent switching to the phosphorescent emission of blue light.
      Additionally, the chiroptical properties of the Zn(II) complexes were also
      studied.

PMID- 17199302
TI  - Preferential solvation within hydrophilic nanocavities and its effect on the
      folding of cholate foldamers.
AB  - The conformations of three cholate foldamers and one molecular basket were
      studied by fluorescence and NMR spectroscopy. In nonpolar solvents (e.g.,
      hexane/ethyl acetate or ethyl acetate) mixed with a small amount of a polar
      solvent (e.g., alcohol or DMSO), the cholate oligomer folded into a helix with
      the hydrophilic faces of the cholates turned inward. Folding created a
      hydrophilic nanocavity preferentially solvated by the entrapped polar solvent
      concentrated from the bulk. This microphase separation of the polar solvent was
      critical to the folding process. Folding was favored by larger-sized polar
      solvent molecules, as fewer such molecules could occupy and solvate the
      nanocavity, thus requiring a smaller extent of phase separation during folding.
      Folding was also favored by smaller/acyclic nonpolar solvent molecules, probably
      because they could avoid contact with the OH/NH groups within the nanocavity
      better than larger/cyclic nonpolar solvent molecules.

PMID- 17199303
TI  - Redox-state-dependent complex formation between pseudoazurin and nitrite
      reductase.
AB  - Bacterial copper-containing nitrite reductase catalyzes the reduction of nitrite
      to nitric oxide as part of the denitrification process. Pseudoazurin interacts
      with nitrite reductase in a transient fashion to supply the necessary electrons.
      The redox-state dependence of complex formation between pseudoazurin and nitrite
      reductase was studied by nuclear magnetic resonance spectroscopy and isothermal
      titration calorimetry. Binding of pseudoazurin in the reduced state is
      characterized by the presence of two binding modes, a slow and a fast exchange
      mode, with a K(d)(app) of 100 microM. In the oxidized state of pseudoazurin,
      binding occurs in a single fast exchange mode with a similar affinity. Metal
      substituted proteins have been used to show that the mode of binding of
      pseudoazurin is independent of the metal charge of nitrite reductase. Contrary to
      what was found for other cupredoxins, protonation of the exposed His ligand to
      the copper of pseudoazurin, His81, does not appear to be involved directly in the
      dual binding mode of the reduced form. A model assuming the presence of a minor
      form of pseudoazurin is proposed to explain the behavior of the complex in the
      reduced state.

PMID- 17199304
TI  - Kinetics of hydrogen atom transfer from (eta(5)-C(5)H(5))Cr(CO)(3)H to various
      olefins: influence of olefin structure.
AB  - Treating (etha(5)-C(5)H(5))Cr(CO)3H (1) or (etha(5)-C(5)H(5))Cr(CO)3D (1-d(1))
      with an excess of olefin containing the opposite isotope generally leads to H/D
      exchange, although hydrogenation is also observed in some cases. Application of
      an appropriate statistical correction to the observed exchange rate gives kH and
      kD, the rate constants for H* (D*) transfer from (etha(5)-C(5)H(5))Cr(CO)(3)H (D)
      to various olefins. The values of kH and kD vary appreciably with the
      substituents on the double bond. Phenyl-substituted olefins accept H* more
      readily than do carbomethoxy-substituted olefins, although the latter accept H*
      more readily than do alkyl-substituted olefins. A methyl substituent on the
      incipient radical site increases k(H) at 323 K by a factor between 5 and 50. A
      methyl substituent on the carbon to which the H* is being transferred decreases
      kH substantially. On the whole, the rate constants for H* transfer reflect steric
      effects as well as the stability of the resulting carbon-centered radicals.

PMID- 17199309
TI  - GC-MS quantification of suspected volatile allergens in fragrances. 2. Data
      treatment strategies and method performances.
AB  - The performances of the GC-MS determination of suspected allergens in fragrance
      concentrates have been investigated. The limit of quantification was
      experimentally determined (10 mg/L), and the variability was investigated for
      three different data treatment strategies: (1) two columns and three
      quantification ions; (2) two columns and one quantification ion; and (3) one
      column and three quantification ions. The first strategy best minimizes the risk
      of determination bias due to coelutions. This risk was evaluated by calculating
      the probability of coeluting a suspected allergen with perfume constituents
      exhibiting ions in common. For hydroxycitronellal, when using a two-column
      strategy, this may statistically occur more than once every 36 analyses for one
      ion or once every 144 analyses for three ions in common.

PMID- 17199308
TI  - Event-specific quantitative detection of nine genetically modified maizes using
      one novel standard reference molecule.
AB  - With the development of genetically modified organism (GMO) detection techniques,
      the Polymerase Chain Reaction (PCR) technique has been the mainstay for GMO
      detection, and real-time PCR is the most effective and important method for GMO
      quantification. An event-specific detection strategy based on the unique and
      specific integration junction sequences between the host plant genome DNA and the
      integrated gene is being developed for its high specificity. This study
      establishes the event-specific detection methods for TC1507 and CBH351 maizes. In
      addition, the event-specific TaqMan real-time PCR detection methods for another
      seven GM maize events (Bt11, Bt176, GA21, MON810, MON863, NK603, and T25) were
      systematically optimized and developed. In these PCR assays, the fluorescent
      quencher, TAMRA, was dyed on the T-base of the probe at the internal position to
      improve the intensity of the fluorescent signal. To overcome the difficulties in
      obtaining the certified reference materials of these GM maizes, one novel
      standard reference molecule containing all nine specific integration junction
      sequences of these GM maizes and the maize endogenous reference gene, zSSIIb, was
      constructed and used for quantitative analysis. The limits of detection of these
      methods were 20 copies for these different GM maizes, the limits of quantitation
      were about 20 copies, and the dynamic ranges for quantification were from 0.05 to
      100% in 100 ng of DNA template. Furthermore, nine groups of the mixed maize
      samples of these nine GM maize events were quantitatively analyzed to evaluate
      the accuracy and precision. The accuracy expressed as bias varied from 0.67 to
      28.00% for the nine tested groups of GM maize samples, and the precision
      expressed as relative standard deviations was from 0.83 to 26.20%. All of these
      indicated that the established event-specific real-time PCR detection systems and
      the reference molecule in this study are suitable for the identification and
      quantification of these GM maizes.

PMID- 17199310
TI  - Evaluation of microwave irradiation for analysis of carbonyl sulfide, carbon
      disulfide, cyanogen, ethyl formate, methyl bromide, sulfuryl fluoride, propylene
      oxide, and phosphine in hay.
AB  - Fumigant residues in hay were "extracted" by microwave irradiation. Hay, in
      gastight glass flasks, was placed in a domestic microwave oven, and fumigants
      were released into the headspace by microwave irradiation. Power settings for
      maximum release of fumigants were determined for carbonyl sulfide (COS), carbon
      disulfide (CS(2)), cyanogen (C(2)N(2)), ethyl formate (EF), methyl bromide
      (CH(3)Br), sulfuryl fluoride (SF), propylene oxide (PPO), and phosphine (PH(3)).
      Recoveries of fortified samples were >91% for COS, CS(2), CH(3)Br, SF, PPO, and
      PH(3) and >76% for C(2)N(2) and EF. Completeness of extraction was assessed from
      the amount of fumigant retained by the microwaved hay. This amount was determined
      from further microwave irradiation and was always small (<5% of the amount
      obtained from the initial procedure). Limits of quantification were <0.1 mg/kg
      for COS, CS(2), C(2)N(2), EF, and PH(3) and <0.5 mg/kg for CH(3)Br, SF, and PPO.
      These low limits were essentially due to the absence of interference from
      solvents and no necessity to inject large-volume gas samples. The microwave
      method is rapid and solvent-free. However, care is required in selecting the
      appropriate power setting. The safety implications of heating sealed flasks in
      microwave ovens should be noted.

PMID- 17199311
TI  - High-resolution (13)C nuclear magnetic resonance spectroscopy pattern recognition
      of fish oil capsules.
AB  - 13C NMR (nuclear magnetic resonance) spectroscopy, in conjunction with
      multivariate analysis of commercial fish oil-related health food products, have
      been used to provide discrimination concerning the nature, composition,
      refinement, and/or adulteration or authentication of the products. Supervised
      (probabilistic neural networks, PNN) and unsupervised (principal component
      analysis, PCA; Kohonen neural networks; generative topographic mapping, GTM)
      pattern recognition techniques were used to visualize and classify samples.
      Simple PCA score plots demonstrated excellent, but not totally unambiguous, class
      distinctions, whereas Kohonen and GTM visualization provided better results.
      Quantitative class predictions with accuracies >95% were achieved with PNN
      analysis. Trout, salmon, and cod oils were completely and correctly classified.
      Samples reported to be salmon oils and cod liver oils did not cluster with true
      salmon and cod liver oil samples, indicating mislabeling or adulteration.

PMID- 17199312
TI  - Hydrolyzable tannins with the hexahydroxydiphenoyl unit and the m-depsidic link:
      HPLC-DAD-MS identification and model synthesis.
AB  - This study was designed to develop efficient analytical tools for the difficult
      HPLC-DAD-MS identification of hydrolyzable tannins in natural tissue extracts.
      Throughout the study of the spectroscopic characteristics of properly synthesized
      stereodefined standards, it was observed that the UV-vis spectra of compounds
      with the m-depsidic link showed a characteristic shoulder at 300 nm, consistent
      with the simple glucogalloyl esters, whereas compounds with the
      hexahydroxydiphenoyl (HHDP) unit gave a diagnostic fragmentation pattern, caused
      by a spontaneous lactonization in the mass spectrometer. These observations were
      confirmed by HPLC-DAD-MS analyses of tannic acid and raspberry extracts, which
      are rich in hydrolyzable tannins with the m-depsidic link and the HHDP unit,
      respectively.

PMID- 17199313
TI  - Enzyme-catalyzed change of antioxidants content and antioxidant activity of
      asparagus juice.
AB  - A pectolytic enzyme preparation from Aspergillus niger (pectinase AN) decreased
      most rutin content and antioxidant activity of asparagus juice. To investigate
      the mechanism of such loss, we analyzed several possible related enzyme
      activities in pectinase AN. We found that the activity of pectinase AN to oxidize
      guaiacol had no significant difference with or without the presence of H2O2; thus
      it was laccase activity, not peroxidase (PO) activity, that pectinase AN
      contained. We did not find any polyphenol oxidase (PPO) activity in pectinase AN.
      Laccase in pectinase AN could be the major cause of loss of rutin and antioxidant
      activity of asparagus juice. When most laccase activity of pectinase AN was
      inactivated after heating at 70 degrees C for 1.5 min and incubated with
      asparagus juice, the loss rate of rutin was only 9% of that treated with unheated
      pectinase AN, and the antioxidant activity was even increased. Rhamnosidase
      activity was detected in pectinase AN and can change rutin in asparagus juice to
      quercetin-3-glucoside, which has higher antioxidant activity than rutin. This may
      explain the increase of antioxidant activity of asparagus juice treated with
      heated pectinase AN that still contained some rhamnosidase activity. The
      discovery of our research is helpful to produce juice with high antioxidant
      activity and high health benefits in the juice industry.

PMID- 17199314
TI  - Relevance of organic farming and effect of climatological conditions on the
      formation of alpha-acids, beta-acids, desmethylxanthohumol, and xanthohumol in
      hop (Humulus lupulus L.).
AB  - The concentrations of alpha-acids, beta-acids, desmethylxanthohumol, and
      xanthohumol were monitored in the hop varieties Admiral (A), Wye Challenger (WC),
      and First Gold (FG) during the harvest seasons of 2003 through 2005. Hops grown
      under an organic regimen were compared to plants grown conventionally in hop
      fields in close vicinity. The concentrations of the key compounds depended very
      much on climatological conditions showing, in general, highest levels in poorest
      weather conditions (2004). Of the three varieties studied, FG was the only one
      showing a clear trend for higher concentrations of secondary metabolites under
      organic growing conditions than under conventional farming conditions.
      Cultivation of A and WC seems to be very sensitive to climatic conditions and
      environmental stresses caused by pests and diseases, thereby leading to various
      results. WC proved to be a rich source of bioactive chalcones, particularly
      desmethylxanthohumol.

PMID- 17199315
TI  - Identification and quantification of glucosinolates in sprouts derived from seeds
      of wild Eruca sativa L. (salad rocket) and Diplotaxis tenuifolia L. (wild rocket)
      from diverse geographical locations.
AB  - The Brassicaceae rocket species Eruca sativa L. (salad rocket) and Diplotaxis
      tenuifolia L. (wild rocket) are consumed throughout the world in salads,
      predominantly the leaves but also the flowers and more recently the sprouts
      (seedlings). Ontogenic profiling of glucosinolates and flavonoids in plants
      derived from commercial seed of these species has previously been done, but no
      studies have been conducted to determine how geographical origin affects
      glucosinolate composition in rocket species. Seeds from wild E. sativa L. and D.
      tenuifolia L. from diverse regions of the world were obtained from gene banks and
      grown under controlled conditions. Sprouts were harvested when they would
      normally be harvested for consumption, and glucosinolates were extracted and
      profiled in these accessions. All of the sprouts from Italian E. sativa L. had
      consistently high total glucosinolate content, with only a few exceptions, and
      also the highest percentage contents of 4-mercaptobutylglucosinolate. In
      contrast, sprouts produced from Central and Eastern European seeds had a much
      higher percentage of 4-methylthiobutylglucosinolate. With a single exception,
      Tunisia, all sprouts produced from North African seeds had very high 4
      methylthiobutylglucosinolate contents. The single sample from China had a high
      total glucosinolate content and glucosinolate profile that was very similar to
      the accessions from Uzbekistan and Pakistan. All of the D. tenuifolia L. sprouts
      had consistently high total glucosinolate contents, and a high percentage of this
      was 4-mercaptobutylglucosinolate. This glucosinolate variation in levels and
      profiles of the rockets can be used for genetic studies, selected breeding, and
      human intervention studies.

PMID- 17199316
TI  - Antioxidant constituents in distillation residue of Awamori spirits.
AB  - Constituents in a distillation residue of Awamori (millet spirits) and their
      antioxidant activity are investigated in this study. The supernatant of the
      distillation residue obtained by centrifugation was partitioned with n-hexane,
      chloroform, ethyl acetate, and n-butanol against water to afford the
      corresponding solubles. Among them, n-hexane and chloroform solubles showed
      higher antioxidant potency than l-ascorbic acid by the bleomycin-Fe method. In
      chloroform solubles, seven cyclic dipeptides were identified along with ethyl 2
      pyrrolidione-5-carboxylate, tyrosol, and ethyl p-hydoroxyphenyllactate.
      Antioxidant activity of ethyl p-hydoroxyphenyllactate was 4.2 times that of l
      ascorbic acid, whereas cyclic dipeptides showed activity 0.89-1.29 times as
      strong as that of l-ascorbic acid. On the other hand, scavenging effect of cyclic
      dipeptides against O(2)(-.) and OH(.) by using electron spin resonance was also
      investigated. In the results, cyclo(l-Ile-l-Pro) showed significantly strong
      inhibitory effect against OH(.) (95.4% at 2.5 x 10-3 M) and cyclo(l-Phe-l-Pro),
      cyclo(l-Pro-l-Val), and cyclo(l-Leu-l-Pro) inhibited OH(.) 64.9, 54.1, and 51.0%,
      respectively, whereas alpha-tocopherol showed 37.7% inhibition, though only a few
      cyclic dipeptides weakly inhibited O(2)(-.).

PMID- 17199317
TI  - Biological activity of acetylated phenolic compounds.
AB  - In recent years an effort has been made to isolate and identify biologically
      active compounds that are included in the Mediterranean diet. The existence of
      naturally occurring acetylated phenolics, as well as studies with synthetic ones,
      provide evidence that acetyl groups could be correlated with their biological
      activity. Platelet activating factor (PAF) is implicated in atherosclerosis,
      whereas its inhibitors seem to play a protective role against cardiovascular
      disease. The aim of this study was to examine the biological activity of
      resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF
      induced washed rabbit platelet aggregation. Acetylation of resveratrol and
      tyrosol was performed, and separation was achieved by HPLC. Acetylated
      derivatives were identified by negative mass spectrometry. The data showed that
      tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas
      diacetylated derivatives induce platelet aggregation. Resveratrol and its mono-
      and triacetylated derivatives exert similar inhibitory activity, whereas the
      diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics
      exert the same or even higher antithrombotic activity compared to the biological
      activity of the initial one.

PMID- 17199318
TI  - Polyphenols and antioxidant capacity of seed coat and cotyledon from Brazilian
      and Peruvian bean cultivars (Phaseolus vulgaris L.).
AB  - Seed coats and cotyledons from 25 Brazilian and 3 Peruvian bean cultivars were
      investigated in relation to their phenolic profiles and antioxidant capacity.
      Condensed tannins, anthocyanins, and flavonols such as kaempferol and quercetin
      glycosides were mostly found in seed coats. Cotyledons were rich in phenolic
      acids, such as ferulic, sinapic, chlorogenic, and other hydroxycinnamic acids. In
      general, the seed coat color pattern and the type of cultivar showed an important
      influence on the variability of phenolic profiles and levels, respectively. Total
      phenolics and antioxidant capacity assessed by the DPPH method were higher in
      seed coats than in cotyledons. The antioxidant capacity had a significant
      correlation with condensed tannins for all samples and with total anthocyanins in
      black and red seed coats, whereas in cotyledons, it was more related to the total
      phenolic content.

PMID- 17199319
TI  - alpha-Glucosidase inhibitory profile of catechins and theaflavins.
AB  - To clarify the postprandial glucose suppression effect of flavonoids, the
      inhibitory effects of catechins and theaflavins against alpha-glucosidase (AGH)
      were examined in this study. It was initially demonstrated that theaflavins and
      catechins preferentially inhibited maltase rather than sucrase in an immobilized
      AGH inhibitory assay system. For the maltase inhibitory effects of theaflavins,
      the effects were observed in descending order of potency of theaflavin (TF)-3-O
      gallate (Gal) > TF-3,3'-di-O-Gal > TF-3'-O-Gal > TF. This suggests that the AGH
      inhibition induced by theaflavins is closely associated with the presence of a
      free hydroxyl group at the 3'-position of TF as well as the esterification of TF
      with a mono-Gal group. In addition, the R-configuration at the 3'-position of TF
      3-O-Gal showed a higher inhibitory activity than the S-configuration. As a result
      of a single oral administration of maltose (2 g/kg) in rats, a significant
      reduction in blood glucose level was observed at a dose of 10 mg/kg of TF-3-O
      Gal, demonstrating for the first time that TF-3-O-Gal can suppress glucose
      production from maltose through inhibition of AGH in the gut.

PMID- 17199320
TI  - Picloram resistance in transgenic tobacco expressing an anti-picloram scFv
      antibody is due to reduced translocation.
AB  - Picloram resistance exhibited by transgenic tobacco (Nicotiana tabacum) plants
      expressing an anti-picloram single-chain variable fragment (scFv) antibody was
      investigated through the study of homozygous lines expressing the antibody. Dose
      response bioassays, using foliar application of picloram, showed that these
      homozygous transgenic plants were resistant to at least 5 g of ai ha-1 picloram
      and grew normally to produce seed, whereas wild-type plants did not survive.
      Although these lines had improved resistance compared with those previously
      reported, significant improvements are still required to achieve field-level
      resistance. Uptake and translocation studies demonstrated that [14C]picloram
      translocation from treated leaves to the apical meristem was reduced in
      transgenic versus wild-type plants. The presence of [14C]picloram visualized by
      autoradiography and quantified by liquid scintillation spectrometry, demonstrated
      the distribution of more picloram in the treated leaf and less in the apical
      meristem of transgenic plants when compared to wild-type plants. No differences
      between transgenic and wild-type plants were found in the distribution of
      [14C]clopyralid, a herbicide with structural similarity to picloram as well as
      the same mechanism of action. No differences were found in the metabolism of
      [14C]picloram. Taken together, these results suggest that reduced translocation
      to the site of action is a major mechanism responsible for picloram resistance in
      tobacco plants expressing this anti-picloram antibody.

PMID- 17199321
TI  - Effect of fining and filtration on the haze formation in bayberry (Myrica rubra
      Sieb. et Zucc.) juice.
AB  - Bayberry juice was fined with the methods of xanthan/chitosan (XC) or
      gelatin/bentonite (GB), and then filtered with diatomaceous earth filtration (DF)
      or ultrafiltration (UF, MWCO 100 kDa). Their effects on juice haze formation were
      investigated. The XC fining method was more effective than the GB method in
      removal of the total monomeric anthocyanin, total phenolics, and protein, with
      less haze formed in the XC fined juice. The DF reduced 2-5% of the total
      phenolics and 21-23% of protein, while UF reduced 19-24% of the total phenolics
      and 34-38% of protein, respectively. The results showed that fining and then UF
      can reduce but cannot eliminate haze formation in bayberry juice. The storage
      temperature was a critical factor affecting haze formation, and the juice was
      more stable when stored at lower temperature (4 degrees C).

PMID- 17199322
TI  - Alkamide stability in Echinacea purpurea extracts with and without phenolic acids
      in dry films and in solution.
AB  - Degradation of the major alkamides in E. purpurea extracts was monitored under
      four different accelerated storage conditions, phenolic-depleted and phenolic
      rich dry E. purpurea extracts and phenolic-depleted and phenolic-rich DMSO E.
      purpurea extracts at 70, 80, and 90 degrees C. Degradation of alkamides followed
      apparent first-order reaction rate kinetics. Alkamides degraded faster in dry
      films than in DMSO solution. The phenolic acids acted as antioxidants by limiting
      the loss of the alkamides in dry E. purpurea extracts. In contrast, E. purpurea
      alkamides in DMSO degraded faster when the phenolic fraction was absent. The
      overall order of degradation rate constants was alkamides 1 approximately 2
      approximately 6 > 9 approximately 8 > 3 approximately 5 approximately 7. The
      energy of activation (Ea) predicted for alkamide degradation averaged 101 +/- 12
      kJ/mol in dry films +/- phenolic acids, suggesting the oxidation mechanism was
      the same under both conditions. In DMSO solutions, Ea values were about one-half
      of those in dry films (61 +/- 14 kJ/mol), suggesting a different mechanism for
      alkamide oxidation in solution compared to dry. Predicted half-lives for
      alkamides in extracts suggested very good stability.

PMID- 17199323
TI  - Effect of moisture content during dry-heating on selected physicochemical and
      functional properties of dried egg white.
AB  - This article addresses the effect of moisture content (0.8-9.9%) during dry
      heating (80 degrees C) on selected physicochemical (solubility, turbidity,
      residual denaturation enthalpy, aggregation, surface hydrophobicity, and
      sulfhydryl content) and functional (foaming ability, foam density, and stability)
      properties of freeze-dried egg white (FDEW). Moisture content during dry-heating
      proved to be a parameter determining the functionality of the resulting egg white
      powder. The degree of conformational changes induced in the egg white proteins by
      dry-heating was strongly dependent on the amount of water present.
      Preferentially, dry-heating at 80 degrees C should be performed on egg white
      powder with a moisture content below 6.8%, as the loss of protein solubility
      above this value is extensive. In addition to insoluble aggregates, soluble,
      strongly stabilized aggregates were also formed, especially at higher moisture
      contents. The decrease in denaturation enthalpy, increase in surface
      hydrophobicity, and exposure of SH groups previously hidden in the protein core
      and their subsequent oxidation were more pronounced at prolonged dry-heating
      times and at higher moisture contents. These conformational changes resulted in
      improved foaming ability and foams with lower density. No effect of dry-heating
      on the foam stability was observed.

PMID- 17199324
TI  - Effect of steam treatment of alperujo on the composition, enzymatic
      saccharification, and in vitro digestibility of alperujo.
AB  - The solid waste from two-phase olive oil extraction or "alperujo" was submitted
      to steam treatment at high pressure or temperature, 200 degrees C for 5 min, in
      the presence and absence of mild acid catalyst. This treatment made easier the
      separation of the solid and liquid fractions. Besides the recovery of certain
      valuable components from the liquid fraction (the antioxidant hydroxytyrosol, low
      molecular weight oligosaccharides, glucose, mannitol, etc.), the major components
      of the solid residue could be also exploited. In this study, changes in
      composition of alperujo due to steam treatment were determined. The process
      reduced appreciably the hemicellulose concentrations (75-88%), removed a
      substantial portion of Klason lignin and protein (50%), and led to an extensive
      solubilization of alperujo (55-67%). Cellulose was very resistant to
      autohydrolysis and acid-catalyzed hydrolysis, so the solid residue was enriched
      in fat (13-18 g/100 g of dry steam-treated alperujo) and cellulose (15-25 g/100 g
      of dry and defatted steam-treated alperujo). The steam-treated material can be
      efficiently saccharified with commercial cellulase. The best hydrolysis yields
      were attained, up to 80%, when the treated material was post-treated with NaOH.
      The possibility of using this steam-treated alperujo in animal feeding was
      evaluated by an in vitro digestibility test, using the pepsin-cellulase method.
      The treatment affected positively the nutritional characteristics of alperujo
      with an increase in its in vitro (dry and organic matter) digestibility (8-10%
      higher than untreated material). In vitro digestibility and cellulose
      accessibility to enzymatic hydrolysis were improved by the alkali post-treatment.

PMID- 17199325
TI  - Syntheses and biological activities of octahydro-1H-cyclopenta[d]pyrimidine
      derivatives.
AB  - Various nitromethylene derivatives were synthesized regioselectively. Compounds
      8a-f were obtained by the reaction of 1-((5-chloropyridin-2-yl)methyl)-2
      (nitromethylene)-octahydro-1H-cyclopenta[d]-pyrimidine (3) with primary amines
      and formaldehyde. The synthesized compounds were identified by 1H NMR, HRMS (EI),
      and IR, and preliminary bioassays indicated that most of them showed moderate
      insecticidal activities against Aphis craccivora. The relationship between
      hydrophobicity and biological activity was also discussed.

PMID- 17199326
TI  - Comparison of proanthocyanidins in commercial antioxidants: grape seed and pine
      bark extracts.
AB  - The major constituents in grape seed and pine bark extracts are
      proanthocyanidins. To evaluate material available to consumers, select lots were
      analyzed using high-performance liquid chromatography, gas chromatography/mass
      spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), gel
      permeation chromatography (GPC), and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS). Atmospheric pressure chemical
      ionization (APCI) LC/MS was used to identify monomers, dimers, and trimers
      present. GC/MS analyses led to the identification of ethyl esters of hexadecanoic
      acid, linoleic acid, and oleic acid, as well as smaller phenolic and terpene
      components. The GPC molecular weight (MW) distribution indicated components
      ranging from approximately 162 to approximately 5500 MW (pine bark less than 1180
      MW and grape seed approximately 1180 to approximately 5000 MW). MALDI-TOF MS
      analyses showed that pine bark did not contain oligomers with odd numbers of
      gallate units and grape seed contained oligomers with both odd and even numbers
      of gallate. Reflectron MALDI-TOF MS identified oligomers up to a pentamer and
      heptamer, and linear MALDI-TOF MS showed a mass range nearly double that of
      reflectron analyses.

PMID- 17199327
TI  - Isolation and structure elucidation of procyanidin oligomers from Saskatoon
      berries (Amelanchier alnifolia).
AB  - Proanthocyanidin oligomers with different degrees of polymerization were isolated
      from Saskatoon berries (Amelanchier alnifolia) by means of gel adsorption and
      normal-phase liquid chromatography. The proanthocyanidins were identified using
      electrospray ionization mass spectrometry, nuclear magnetic resonance
      spectroscopy, and thiolytic degradation coupled with reversed-phase liquid
      chromatography. The results established that Saskatoon berries contain
      proanthocyanidins from dimers through heptamers and higher polymers. Saskatoon
      proanthocyanidins are essentially of procyanidin type, consisting mainly of
      epicatechin units linked by B-type bonds. The simple procyanidin profile of
      Saskatoon berries allowed the procyanidins to be separated precisely according to
      their degrees of polymerization. In the future they can be used as standard
      compounds for qualitative and quantitative analysis of procyanidins as well as
      for elucidation of the biological activities of proanthocyanidins.

PMID- 17199328
TI  - New method to evaluate water-soluble antioxidant activity based on protein
      structural change.
AB  - A simple method to evaluate antioxidant activities of water-soluble ingredients
      of foods has been developed. Protective effects of antioxidants against
      hypochlorite radical or hydroxyl radical have been studied by comparing changes
      in absorbance of myoglobin (a standard reference) at 409 nm. Protective ratio,
      defined by absorbance changes of myoglobin with or without the antioxidant, was a
      good indicator to quantitatively evaluate the antioxidant activity against the
      hypochlorite radical or the hydroxyl radical, respectively. Radar charts
      indicating the antioxidant activities against DPPH (1,1-diphenyl-2
      picrylhydrazyl), hypochlorite radical, and hydroxyl radical clearly
      differentiated the characteristics of five antioxidants including carnosine,
      glutathione, and vitamin C. By comparison of the radar charts, antioxidant
      activity of bonito meat hydrolysate was found to have similar characteristics to
      that of carnosine. The simple method proposed in this study would be useful for
      evaluating and characterizing the activities of water-soluble antioxidants
      contained in various food materials.

PMID- 17199329
TI  - Photoinduced generation of 2,3-butanedione from riboflavin.
AB  - The volatile compound formation from riboflavin solution of a phosphate buffer
      (0.1 M, pH 6.5) under light for 15 h was studied by SPME-GC and SPME-GC/MS
      analysis. Only one major compound in the riboflavin solution was formed and
      increased as the light exposure time increased. The light-exposed riboflavin
      solution had a buttery odor. The compound of riboflavin solution under light was
      analyzed by gas chromatography and olfactometry. The major volatile compound
      eluted from the gas chromatograph had a buttery odor. The buttery odor compound
      was positively identified as 2,3-butanedione by a combination of gas
      chromatographic retention time, mass spectrum, and odor evaluation of authentic
      2,3-butanedione. The addition of sodium azide, a singlet oxygen quencher, to
      riboflavin solution minimized the formation of the buttery odor compound. Singlet
      oxygen was involved in the formation of the buttery odor. The 2,3-butanedione was
      produced from the reaction between riboflavin and singlet oxygen. Singlet oxygen
      was formed from triplet oxygen by riboflavin photosensitization mechanism. This
      is the first reported oxidation reaction between riboflavin and singlet or
      triplet in food and biological systems.

PMID- 17199330
TI  - Preparation and characterization of water/oil and water/oil/water emulsions
      containing biopolymer-gelled water droplets.
AB  - The purpose of this study was to create water-in-oil (W/O) and water-in-oil-in
      water (W/O/W) emulsions containing gelled internal water droplets. Twenty weight
      percent W/O emulsions stabilized by a nonionic surfactant (6.4 wt % polyglycerol
      polyricinoleate, PGPR) were prepared that contained either 0 or 15 wt % whey
      protein isolate (WPI) in the aqueous phase, with the WPI-containing emulsions
      being either unheated or heated (80 degrees C for 20 min) to gel the protein.
      Optical microscopy and sedimentation tests did not indicate any significant
      changes in droplet characteristics of the W/O emulsions depending on WPI content
      (0 or 15%), shearing (0-7 min at constant shear), thermal processing (30-90
      degrees C for 30 min), or storage at room temperature (up to 3 weeks). W/O/W
      emulsions were produced by homogenizing the W/O emulsions with an aqueous Tween
      20 solution using either a membrane homogenizer (MH) or a high-pressure valve
      homogenizer (HPVH). For the MH the mean oil droplet size decreased with
      increasing number of passes, whereas for the HPVH it decreased with increasing
      number of passes and increasing homogenization pressure. The HPVH produced
      smaller droplets than the MH, but the MH produced a narrower particle size
      distribution. All W/O/W emulsions had a high retention of water droplets (>95%)
      within the larger oil droplets after homogenization. This study shows that W/O/W
      emulsions containing oil droplets with gelled water droplets inside can be
      produced by using MH or HPVH.

PMID- 17199331
TI  - Growth suppression of human cancer cells by polyphenolics from sweetpotato
      (Ipomoea batatas L.) leaves.
AB  - Sweetpotato leaves (Ipomoea batatas L.) contain a high content of polyphenolics
      that consist of caffeic acid, chlorogenic acid, 3,4-di-O-caffeoylquinic acid, 3,5
      di-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, and 3,4,5-tri-O
      caffeoylquinic acid. We investigated the suppression of the proliferation of
      selected human cancer cells by phenolic compounds isolated from sweetpotato leaf.
      The human cancer cells used in this research included a stomach cancer (Kato
      III), a colon cancer (DLD-1), and a promyelocytic leukemia cell (HL-60). Caffeic
      acid and di- and tricaffeoylquinic acids dose-dependently depressed cancer cell
      proliferation, and the difference in sensitivity between caffeoylquinic acid
      derivatives and each kind of cancer cell was observed. Specifically, 3,4,5-tri-O
      caffeoylquinic acid effectively depressed the growth of three kinds of cancer
      cells, and caffeic acid had an exceptionally higher effect against HL-60 cells
      than other di- and tricaffeoylquinic acids. In attempting to clarify the
      mechanism of growth suppression with the addition of the apoptotic inhibitor N
      ethylmaleimide, we observed that the nuclear granulation in 3,4,5-tri-O
      caffeoylquinic acid-treated HL-60 cells suggested apoptosis induction. This
      effect was confirmed by DNA fragmentation, an increase of caspase-3 activity, and
      expression of c-Jun. Growth suppression of HL-60 cells by 3,4,5-tri-O
      caffeoylquinic acid was determined to be the result of apoptotic death of the
      cells. These results indicate that 3,4,5-tri-O-caffeoylquinic acid may have
      potential for cancer prevention.

PMID- 17199332
TI  - Using the histogram test to quantify reaction coordinate error.
AB  - Many schemes for calculating reaction rates and free energy barriers require an
      accurate reaction coordinate, but it is difficult to quantify reaction coordinate
      accuracy for complex processes like protein folding and nucleation. The histogram
      test, based on estimated committor probabilities, is often used as a qualitative
      indicator for good reaction coordinates. This paper derives the mean and variance
      of the intrinsic committor distribution in terms of the mean and variance of the
      histogram of committor estimates. These convenient formulas enable the first
      quantitative calculations of reaction coordinate error for complex systems. An
      example shows that the approximate transition state surface from Peters' and
      Trout's reaction coordinate for nucleation in the Ising model gives a mean
      committor probability of 0.495 and a standard deviation of 0.042.

PMID- 17199333
TI  - Relativistic effective core potential calculations of Hg and eka-Hg (E112)
      interactions with gold: spin-orbit density functional theory modeling of Hg-Aun
      and E112-Aun systems.
AB  - Interactions of eka-Hg (E112) and Hg atoms with small gold clusters were studied
      in the frame of the relativistic effective core potential model using the density
      functional theory (DFT) approach incorporating spin-dependent (magnetic)
      interactions. The choice of the exchange-correlation functional was based on a
      comparison of the results of DFT and large-scale coupled cluster calculations for
      E112Au and HgAu at the scalar relativistic level. A close similarity between the
      E112Aun and HgAun equilibrium structures was observed. The E112 binding energies
      on Aun are typically smaller than those for Hg by ca. 25%-32% and the equilibrium
      E112-Au separations are always slightly larger than their Hg-Au counterparts.

PMID- 17199334
TI  - Analogies and differences between two ways to evaluate the global hardness.
AB  - The weight of the energetic components (electronic kinetic, electron-nucleus and
      electron-electron Coulombic, and correlation energies) of the ionization
      potential, electron affinity, chemical potential, and global hardness is
      evaluated and contrasted with the energetic components of the hardness kernel and
      the experimental values of these properties for 40 systems. The contrast of the
      hardness terms obtained from finite difference and hardness kernel gives some
      insight on the possible implications to differentiate the electronic energy with
      respect to the number electrons or the electron density.

PMID- 17199335
TI  - Quantal cumulant dynamics: general theory.
AB  - The authors have derived coupled equations of motion of cumulants that consist of
      a symmetric-ordered product of the position and momentum fluctuation operators in
      one dimension. The key point is the utilization of a position shift operator
      acting on a potential operator, where the expectation value of the shift operator
      is evaluated using the cumulant expansion technique. In particular, the equations
      of motion of the second-order cumulant and the expectation values of the position
      and momentum operators are given. The resultant equations are expressed by those
      variables and a quantal potential that consists of an exponential function of the
      differential operators and the original potential. This procedure enables us to
      perform quantal (semiclassical) dynamics in one dimension. In contrast to a
      second-order quantized Hamilton dynamics by Prezhdo and Pereverzev which
      conserves the total energy only with an odd-order Taylor expansion of the
      potential [J. Chem. Phys. 116, 4450 (2002); 117, 2995 (2002)], the present
      quantal cumulant dynamics method exactly conserves the energy, even if a second
      order approximation of the cumulants is adopted, because the present scheme does
      not truncate the given potential. The authors propose three schemes, (i) a
      truncation, (ii) a summation of derivatives, and (iii) a convolution method, for
      evaluating the quantal potentials for several types of potentials. The numerical
      results show that although the truncation method preserves the energy to some
      degree, the trajectory obtained gradually deviates from that of the summation
      scheme after 2000 steps. The phase space structure obtained by the truncation
      scheme is also different from that of the summation scheme in a strongly
      anharmonic region.

PMID- 17199336
TI  - Comparative study of perturbative methods for computing electron transfer
      tunneling matrix elements with a nonorthogonal basis set.
AB  - The authors consider the problem of computing tunneling matrix elements for
      bridge-mediated electron transfer reactions using the Lowdin [J. Math. Phys. 3,
      969 (1962); J. Mol. Spectrosc. 13, 326 (1964)] projection-iteration technique
      with a nonorthogonal basis set. They compare the convergence properties of two
      different Lowdin projections, one containing the overlap matrix S and the other
      containing the inverse S-1 in the projected Hamiltonian. It was suggested in the
      literature that the projected Hamiltonian with S-1 has better convergence
      properties compared to the projected Hamiltonian with S. The authors test this
      proposal using a simple analytical model, and ab initio Hartree-Fock calculations
      on different molecules with several types of basis sets. Their calculations show
      that, for Gaussian-type basis sets, the projected Hamiltonian containing S has
      the best convergence properties, especially for diffuse basis sets and in the
      strong coupling limit. The limit of diffuse basis sets is relevant to tunneling
      matrix element calculations involving excited states and anionic electron
      transfer.

PMID- 17199337
TI  - Determination of complex absorbing potentials from the electron self-energy.
AB  - The electronic conductance of a molecule making contact to electrodes is
      determined by the coupling of discrete molecular states to the continuum
      electrode density of states. Interactions between bound states and continua can
      be modeled exactly by using the (energy-dependent) self-energy or approximately
      by using a complex potential. We discuss the relation between the two approaches
      and give a prescription for using the self-energy to construct an energy
      independent, nonlocal, complex potential. We apply our scheme to studying single
      electron transmission in an atomic chain, obtaining excellent agreement with the
      exact result. Our approach allows us to treat electron-reservoir couplings
      independent of single-electron energies, allowing for the definition of a one
      body operator suitable for inclusion into correlated electron transport
      calculations.

PMID- 17199338
TI  - H/D isotope effect on porphine and porphycene molecules with multicomponent
      hybrid density functional theory.
AB  - To analyze the H/D isotope effect on porphine and porphycene molecules including
      the protonic/deuteronic quantum nature and electron correlation efficiently, the
      authors have developed the new scheme of the multicomponent hybrid density
      functional theory [MC_(HF+DFT)]. The optimized geometries of porphine,
      porphycene, and these deuterated isotopomers by our MC_(HF+DFT) method are in
      good agreement with the experimental "high-symmetric" structures, contrary to the
      "low-symmetric" geometries optimized by pure multicomponent Hartree-Fock method.
      The optimized geometries for HD-porphine and HD-porphycene molecules, in which an
      inner hydrogen is replaced to a deuterium, are found to be low symmetric. Such
      drastic geometrical change induces the electronic polarization, and gives rise to
      the slight dipole moment values in these HD species. Their results clearly
      indicate that the difference of the nuclear quantum nature between inner proton
      and inner deuteron directly influences the molecular geometry and electronic
      structure.

PMID- 17199339
TI  - Combining explicitly correlated R12 and Gaussian geminal electronic structure
      theories.
AB  - Explicitly correlated R12 methods using a single short-range correlation factor
      (also known as F12 methods) have dramatically smaller basis set errors compared
      to the standard wave function counterparts, even when used with small basis sets.
      Correlations on several length scales, however, may not be described efficiently
      with one correlation factor. Here the authors explore a more general MP2-R12
      method in which each electron pair uses a set of (contracted) Gaussian-type
      geminals (GTGs) with fixed exponents, whose coefficients are optimized linearly.
      The following features distinguish the current method from related explicitly
      correlated approaches published in the literature: (1) only two-electron
      integrals are needed, (2) the only approximations are the resolution of the
      identity and the generalized Brillouin condition, (3) only linear parameters are
      optimized, and (4) an arbitrary number of (non-)contracted GTGs can appear. The
      present method using only three GTGs and a double-zeta quality basis computed
      valence correlation energies for a set of 20 small molecules only 2.2% removed
      from the basis set limit. The average basis set error reduces to 1.2% using a
      near-complete set of seven GTGs with the double-zeta basis set. The conventional
      MP2 energies computed with much larger quadruple, quintuple, and sextuple basis
      sets all had larger average errors: 4.6%, 2.4%, and 1.5%, respectively. The new
      method compares well to the published MP2-R12 method using a single Slater-type
      geminal (STG) correlation factor. For example, the average basis set error in the
      absolute MP2-R12 energy obtained with the exp(-r12) correlation factor is 1.7%.
      Correlation contribution to atomization energies evaluated with the present
      method and with the STG-based method only required a double-zeta basis set to
      exceed the precision of the conventional sextuple-zeta result. The new method is
      shown to always be numerically stable if linear dependencies are removed from the
      two-particle basis and the zeroth-order Hamiltonian matrix is made positive
      definite.

PMID- 17199340
TI  - Quantum mechanical polarizable force field (QMPFF3): refinement and validation of
      the dispersion interaction for aromatic carbon.
AB  - The authors have recently introduced a general, polarizable force field QMPFF
      fitted solely to high-level quantum mechanical data for simulations of
      biomolecular systems. Here the authors demonstrate using an advanced version
      QMPFF3 how the problem of insufficient accuracy of the MP2-based training set for
      the aromatic carbon atom type can be effectively solved by a simple model
      correction using state-of-the-art CCSD(T) data. The approach demonstrates
      excellent transferability, which is confirmed for three phases of matter by
      accurate calculations of the second virial coefficient for benzene vapor and
      various properties of liquid benzene and polyaromatic hydrocarbon crystals.

PMID- 17199341
TI  - Automatic integration of the reaction path using diagonally implicit Runge-Kutta
      methods.
AB  - The diagonally implicit Runge-Kutta framework is shown to be a general form for
      constructing stable, efficient steepest descent reaction path integrators, of any
      order. With this framework tolerance driven, adaptive step-size methods can be
      constructed by embedding methods to obtain error estimates of each step without
      additional computational cost. There are many embedded and nonembedded,
      diagonally implicit Runge-Kutta methods available from the numerical analysis
      literature and these are reviewed for orders two, three, and four. New embedded
      methods are also developed which are tailored to the application of reaction path
      following. All integrators are summarized and compared for three systems: the
      Muller-Brown [Theor. Chem. Acta 53, 75 (1979)] potential and two gas phase
      chemical reactions. The results show that many of the methods are capable of
      integrating efficiently while reliably keeping the error bound within the desired
      tolerance. This allows the reaction path to be determined through automatic
      integration by only specifying the desired accuracy and transition state.

PMID- 17199342
TI  - Simple Hamiltonians which exhibit drastic failures by variational determination
      of the two-particle reduced density matrix with some well known N
      representability conditions.
AB  - Calculations on small molecular systems indicate that the variational approach
      employing the two-particle reduced density matrix (2-RDM) as the basic unknown
      and applying the P, Q, G, T1, and T2 representability conditions provides an
      accuracy that is competitive with the best standard ab initio methods of quantum
      chemistry. However, in this paper we consider a simple class of Hamiltonians for
      which an exact ground state wave function can be written as a single Slater
      determinant and yet the same 2-RDM approach gives a drastically nonrepresentable
      result. This shows the need for stronger representability conditions than the
      mentioned ones.

PMID- 17199343
TI  - Efficient correlation-corrected vibrational self-consistent field computation of
      OH-stretch frequencies using a low-scaling algorithm.
AB  - The authors present a new computational scheme to perform accurate and fast
      direct correlation-corrected vibrational self-consistent field (CC-VSCF)
      computations for a selected number of vibrational modes, which is aimed at
      predicting a few vibrations in large molecular systems. The method is based on a
      systematic selection of vibrational mode-mode coupling terms, leading to the
      direct ab initio construction of a sparse potential energy surface. The
      computational scaling of the CC-VSCF computation on the generated surface is then
      further reduced by using a screening procedure for the correlation-correction
      contributions. The proposed method is applied to the computation of the OH
      stretch frequency of five aliphatic alcohols. The authors investigate the
      influence of different pseudopotential and all-electron basis sets on the quality
      of the correlated potential energy surfaces computed and on the OH-stretch
      frequencies calculated for each surface. With the help of these test systems, the
      authors show that their method offers a computational scaling that is two orders
      of magnitude lower than a standard CC-VSCF method and that it is of equal
      accuracy.

PMID- 17199344
TI  - Explicitly intruder-free valence-universal multireference coupled cluster theory
      as applied to ionization spectroscopy.
AB  - Although it is quite promising to compute the spectroscopic energies [say,
      ionization potential (IP)] via the traditional valence-universal multireference
      coupled cluster (VUMRCC) method based on the description of the complete model
      space being seriously plagued by the perennial intruder state problem, the
      eigenvalue independent partitioning (EIP) based VUMRCC (coined as EIP-MRCC)
      method is quite effective to predict the spectroscopic energies in an intruder
      free manner. Hence, the EIP-MRCC method is suitable for generating both the
      principal IPs and the satellite IPs of the inner-valence region. An EIP strategy
      converts the nonlinear VUMRCC equations for M(m,n) dimensional model space of m
      hole and n particle to a non-Hermitian eigenproblem of larger dimension whose
      M(m,n) roots are only physically meaningful. To increase the quality of the
      computed energy differences in the sense of chemical accuracy and to locate the
      correct position of it in the spectrum, the inclusion of higher-body cluster
      operators on top of all the standard singles-doubles is not the only pivotal
      issue, the effect of the size of the basis set is also equally important. This
      paper illustrates these issues by calculating the principal and satellite IPs of
      HF and HCl molecules using various basis sets (viz., Dunning's cc-pVDZ, cc-pVTZ,
      and cc-pVQZ) via EIP-MRCC method with full inclusion of triples (abbreviated as
      EIP-MRCCSDT). The results seem quite encouraging in comparison with the
      experimental values. The controversial 2Pi satellite at 28.67 eV of HCl of
      Svensson et al. [J. Chem. Phys. 89, 7193 (1988)] is also reported.

PMID- 17199345
TI  - Photoelectron imaging of I2- at 5.826 eV.
AB  - We report the anion photoelectron spectrum of I2- taken at 5.826 eV detachment
      energy using velocity mapped imaging. The photoelectron spectrum exhibits bands
      resulting from transitions to the bound regions of the X 1Sigmag+(0g+), A'
      3Piu(2u), A 3Piu(1u), and B 3Piu(0u+) electronic states as well as bands
      resulting from transitions to the repulsive regions of several I2 electronic
      states: the B' 3Piu(0u-), B" 1Piu(1u), 3Pig(2g), a 3Pig(1g), 3Pig(0g-), and C
      3Sigmau+(1u) states. We simulate the photoelectron spectrum using literature
      parameters for the I2- and I2 ground and excited states. The photoelectron
      spectrum includes bands resulting from transitions to several high-lying excited
      states of I2 that have not been seen experimentally: 3Pig(0g-), 1Pig3(1g), 1
      3Sigmag-3(0g+), and the 1Sigmag-3(0u-) states of I2. Finally, the photoelectron
      spectrum at 5.826 eV allows for the correction of a previous misassignment for
      the vertical detachment energy of the I2 B 3Piu(0u+) state.

PMID- 17199346
TI  - Interaction of low-energy electrons with the purine bases, nucleosides, and
      nucleotides of DNA.
AB  - The authors report results from computational studies of the interaction of low
      energy electrons with the purine bases of DNA, adenine and guanine, as well as
      with the associated nucleosides, deoxyadenosine and deoxyguanosine, and the
      nucleotide deoxyadenosine monophosphate. Their calculations focus on the
      characterization of the pi* shape resonances associated with the bases and also
      provide general information on the scattering of slow electrons by these targets.
      Results are obtained for adenine and guanine both with and without inclusion of
      polarization effects, and the resonance energy shifts observed due to
      polarization are used to predict pi* resonance energies in associated nucleosides
      and nucleotides, for which static-exchange calculations were carried out. They
      observe slight shifts between the resonance energies in the isolated bases and
      those in the nucleosides.

PMID- 17199347
TI  - Relativistic density functional calculations using two-spinor minimax finite
      element method and linear combination of atomic orbitals for ZnO, CdO, HgO, UubO
      and Cu2, Ag2, Au2, Rg2.
AB  - In previous work the authors have presented a highly accurate two-spinor fully
      relativistic solution of the two-center Coulomb problem utilizing the finite
      element method (FEM) and furthermore developed a relativistic minimax two-spinor
      linear combination of atomic orbitals (LCAO). In the present paper the authors
      present Dirac-Fock-Slater (DFS-) density functional calculations for two-atomic
      molecules up to super heavy systems using the fully nonlinear minimax FEM and the
      minimax LCAO in its linearized approximation (linear approximation to
      relativistic minimax). The FEM gives highly accurate benchmark results for the
      DFS functional. Especially considering molecules with up to super heavy atoms
      such as UubO and Rg2, the authors found that LCAO fails to give the correct
      systematic trends. The accurate FEM results shed a new light on the quality of
      the DFS-density functional.

PMID- 17199348
TI  - Mixed quantum-classical molecular dynamics simulation of vibrational relaxation
      of ions in an electrostatic field.
AB  - The vibrational relaxation of ions in low-density gases under the action of an
      electrostatic field is reproduced through a molecular dynamics simulation method.
      The vibration is treated though quantum mechanics and the remaining degrees of
      freedom are considered classical. The procedure is tested through comparison
      against analytic results for a two-dimensional quantum model and by studying
      energy exchange during binary ion-atom collisions. Finally, the method has been
      applied successfully to the calculation of the mobility and the vibrational
      relaxation rate of O2+ in Kr as a function of the mean collision energy using a
      model interaction potential that reproduces the potential minimum of a previously
      known ab initio potential surface. The calculation of the steady mean vibrational
      motion of the ions in (flow) drift tubes seems straightforward, though at the
      expense of large amounts of computer time.

PMID- 17199349
TI  - Nonlinear effects on solvation dynamics in simple mixtures.
AB  - The authors applied the time dependent density functional method (TDDFM) and a
      linear model to solvation dynamics in simple binary solvents. Changing the solute
      solvent interactions at t=0, the authors calculated the time evolution of density
      fields for solvent particles after the change (t>0) by the TDDFM and linear
      model. First, the authors changed the interaction of only one component of
      solvents. In this case, the TDDFM showed that the solvation time decreased
      monotonically with a mole fraction of the solvent strongly interacting with the
      solute. The monotonical decreases agreed with experimental results, while the
      linear model did not reproduce these results. The authors also calculated the
      solvation time by changing the interaction of both components. The calculation
      showed that the mole fraction dependence had the peak. The TDDFM presented a much
      higher peak than the linear model. The difference between the TDDFM and the
      linear model was caused by a nonlinear effect on an exchange process of solvent
      particles.

PMID- 17199350
TI  - Excess-entropy-based anomalies for a waterlike fluid.
AB  - Many thermodynamic and dynamic properties of water display unusual behavior at
      low enough temperatures. In a recent study, Yan et al. [Phys. Rev. Lett. 95,
      130604 (2005)] identified a spherically symmetric two-scale potential that
      displays many of the same anomalous properties as water. More specifically, for
      select parametrizations of the potential, one finds that the regions where
      isothermal compression anomalously (i) decreases the fluid's structural order,
      (ii) increases its translational self-diffusivity, and (iii) increases its
      entropy form nested domes in the temperature-density plane. These property
      relationships are similar to those found for more realistic models of water. In
      this work, the authors provide evidence that suggests that the anomalous regions
      specified above can all be linked through knowledge of the excess entropy.
      Specifically, the authors show how entropy scaling relationships developed by
      Rosenfeld [Phys. Rev. A 15, 2545 (1977)] can be used to describe the region of
      diffusivity anomalies and to predict the state conditions for which anomalous
      viscosity and thermal conductivity behavior might be found.

PMID- 17199351
TI  - Heat capacity, Raman, and Brillouin scattering studies of M2O-MgO-WO3-P2O5
      glasses (M=K,Rb).
AB  - The authors report the results of temperature-dependent Brillouin scattering from
      both transverse and longitudinal acoustic waves, heat capacity studies as well as
      room temperature Raman scattering studies on M2O-MgO-WO3-P2O5 glasses (M=K,Rb).
      These results were used to obtain information about structure and various
      properties of the studied glasses such as fragility, elastic moduli, ratio of
      photoelastic constants, and elastic anharmonicity. They have found that both
      glasses have similar properties but replacement of K+ ions by Rb+ ions in the
      glass network leads to decrease of elastic parameters and P44 photoelastic
      constant due to increase of fragility. Based on Brillouin spectroscopy they show
      that a linear correlation between longitudinal and shear elastic moduli holds
      over a large temperature range. This result supports the literature data that the
      Cauchy-type relation represents a general rule for amorphous solids. An analysis
      of the Boson peak revealed that the form of the frequency distribution of the
      excess density of states is in agreement with the Euclidean random matrix theory.
      The reason of the observed shift of the maximum frequency of the Boson peak when
      K+ ions are substituted for Rb+ ions is also briefly discussed.

PMID- 17199352
TI  - Changes in thermodynamic quantities upon contact of two solutes in solvent under
      isochoric and isobaric conditions.
AB  - The changes in excess thermodynamic quantities upon the contact of two solutes
      immersed in a solvent are analyzed using the radial-symmetric and three
      dimensional versions of the integral equation theory. A simple model mimicking a
      solute in water is employed. The solute-solute interaction energy is not included
      in the calculations. Under the isochoric condition, the solute contact always
      leads to a positive entropy change irrespective of the solute solvophobicity or
      solvophilicity. The energy change is negative for solvophobic solutes while it is
      positive for solvophilic ones. Under the isobaric condition, the contact of
      solvophobic solutes results in system-volume compression but that of solvophilic
      ones gives rise to expansion. Effects of the compression and expansion on the
      changes in enthalpy and entropy are enlarged with rising temperature. When the
      solute solvophobicity is sufficiently high, the entropy change (multiplied by the
      absolute temperature) can become negative due to the compression, except at low
      temperatures with the result of an even larger, negative enthalpy change. The
      expansion in the case of solvophilic solutes leads to a large, positive entropy
      change accompanied by an even larger, positive enthalpy change. The changes in
      enthalpy and entropy are strongly dependent on the temperature. However, the
      changes in enthalpy and entropy are largely cancelled out and the temperature
      dependency of the free-energy change is much weaker. The authors also discuss
      possible relevance to the enthalpy-entropy compensation experimentally known for
      a variety of physicochemical processes in aqueous solution such as protein
      folding.

PMID- 17199353
TI  - Contact effects on electronic transport in donor-bridge-acceptor complexes
      interacting with a thermal bath.
AB  - A model for electron transfer in donor-bridge-acceptor complexes with electronic
      coupling to nuclear bridge modes is studied using the Redfield formulation. We
      demonstrate that the transport mechanism through the molecular bridge is
      controlled by the location of the electronic-nuclear coupling term along the
      bridge. As the electronic-nuclear coupling term is shifted from the
      donor/acceptor-bridge contact sites into the bridge, the mechanism changes from
      kinetic transport (incoherent, thermally activated, and bridge-length
      independent) to coherent tunneling oscillations. This study joins earlier works
      aiming to explore the factors which control the mechanism of electronic transport
      through molecular bridges and molecular wires.

PMID- 17199354
TI  - Simulation studies of ionic liquids: orientational correlations and static
      dielectric properties.
AB  - The ionic liquids BMIM+I-, BMIM+BF4-, and BMIM+PF6- were simulated by means of
      the molecular dynamics method over a time period of more than 100 ns. Besides the
      common structural analysis, e.g., radial distribution functions and three
      dimensional occupancy plots, a more sophisticated orientational analysis was
      performed. The angular correlation functions g(00)110(r) and g(00)101(r) are the
      first distance dependent coefficients of the pairwise orientational distribution
      function g(rij,Omega1,Omega2,Omega12). These functions help to interpret the
      three dimensional plot and reveal interesting insights into the local structure
      of the analyzed ionic liquids. Furthermore, the collective network of ionic
      liquids can be characterized by the Kirkwood factor Gkappa(r) [J. Chem. Phys. 7,
      911 (1939)]. The short-range behavior (r<10 A) of this factor may be suitable to
      predict the water miscibility of the ionic liquid. The long-range limit of
      Gkinfinity is below 1 which demonstrates the strongly coupled nature of the ionic
      liquid networks. In addition, this factor relates the orientational structure and
      the dielectric properties of the ionic liquids. The static dielectric constant
      epsilon(omega=0) for the simulated system is 8.9-9.5. Since in ionic liquids the
      very same molecule contributes to the total dipole moment as well as carries a
      net charge, a small, but significant contribution of the cross term between the
      total dipole moment and the electric current to epsilon(omega=0) is observed.

PMID- 17199355
TI  - Vibrational energy relaxation of azide in water.
AB  - Vibrational lifetimes of the asymmetric stretch fundamental of azide anion in
      normal and heavy water have been measured experimentally, with results in the
      range of a few picoseconds. This is an interesting problem for theoretical study
      because of the competition between intramolecular (relaxation to the other
      excited vibrational states of azide) and purely intermolecular (relaxation to
      azide's ground vibrational state) pathways. In addition it is important to
      understand the origin of the solvent isotope effect. Building on the seminal work
      of Morita and Kato [J. Chem. Phys. 109, 5511 (1998)], the authors develop a
      simple model based on a two-dimensional description of the azide stretching
      vibrations. A novel aspect of their theory is the use of an "on-the-fly"
      optimized quantum mechanical/molecular mechanical approach to calculate the
      system-bath coupling. Their theoretical lifetimes are in good agreement with
      experiment for azide in both normal and heavy water. They find that the
      predominant relaxation pathway is intramolecular. The solvent isotope effect
      arises from the different librational frequencies in normal and heavy water.

PMID- 17199356
TI  - Phenol-benzene complexation dynamics: quantum chemistry calculation, molecular
      dynamics simulations, and two dimensional IR spectroscopy.
AB  - Molecular dynamics (MD) simulations and quantum mechanical electronic structure
      calculations are used to investigate the nature and dynamics of the phenol
      benzene complex in the mixed solvent, benzene/CCl4. Under thermal equilibrium
      conditions, the complexes are continuously dissociating and forming. The MD
      simulations are used to calculate the experimental observables related to the
      phenol hydroxyl stretching mode, i.e., the two dimensional infrared vibrational
      echo spectrum as a function of time, which directly displays the formation and
      dissociation of the complex through the growth of off-diagonal peaks, and the
      linear absorption spectrum, which displays two hydroxyl stretch peaks, one for
      the complex and one for the free phenol. The results of the simulations are
      compared to previously reported experimental data and are found to be in quite
      reasonable agreement. The electronic structure calculations show that the complex
      is T shaped. The classical potential used for the phenol-benzene interaction in
      the MD simulations is in good accord with the highest level of the electronic
      structure calculations. A variety of other features is extracted from the
      simulations including the relationship between the structure and the projection
      of the electric field on the hydroxyl group. The fluctuating electric field is
      used to determine the hydroxyl stretch frequency-frequency correlation function
      (FFCF). The simulations are also used to examine the number distribution of
      benzene and CCl4 molecules in the first solvent shell around the phenol. It is
      found that the distribution is not that of the solvent mole fraction of benzene.
      There are substantial probabilities of finding a phenol in either a pure benzene
      environment or a pure CCl4 environment. A conjecture is made that relates the
      FFCF to the local number of benzene molecules in phenol's first solvent shell.

PMID- 17199357
TI  - Nuclear spin relaxation of sodium cations in bacteriophage Pf1 solutions.
AB  - The nuclear magnetic resonance (NMR) spectra for the I=3/2 23Na cation dissolved
      into filamentous bacteriophage Pf1 solutions display line splittings and
      relaxation times consistent with an interaction between the 23Na nuclear
      quadrupole moment and the electric field gradient produced by the negatively
      charged Pf1 particles. The 23Na NMR line splittings and relaxation rates
      corresponding to magnetization recovery and single, double, and triple quantum
      coherence decays are measured in Pf1 solutions and compared to theoretical
      values. The deviation of the observed dc spectral density J0 from the equal first
      harmonic J(omega0) and second harmonic J(2omega0) values as J(omega0)=J(2omega0)
      not equal to J0 in these solutions suggests that ion migration in the electric
      field gradient of the Pf1 particles produces an anisotropic relaxation mechanism.
      Correlation functions and thus spectral densities for this process are calculated
      from solutions to the Fokker-Planck equation for radial motion in an electric
      potential and used to estimate measured relaxation rates. Appropriate electric
      potentials are generated from the solutions to the Poisson-Boltzmann equation for
      a charged Pf1 particle in aqueous phase, functions that lead to theoretical
      estimates of NMR line splittings consistent with experimental observations.

PMID- 17199358
TI  - Are recent water models obtained by fitting diffraction data consistent with
      infrared/Raman and x-ray absorption spectra?
AB  - X-ray absorption (XA) spectra have been computed based on water structures
      obtained from a recent fit to x-ray and neutron diffraction data using models
      ranging from symmetrical to asymmetrical local coordination of the water
      molecules [A. K. Soper, J. Phys.: Condens. Matter 17, S3273 (2005)]. It is found
      that both the obtained symmetric and asymmetric structural models of water give
      similar looking XA spectra, which do not match the experiment. The fitted models
      both contain unphysical structures that are allowed by the diffraction data,
      where, e.g., hydrogen-hydrogen interactions may occur. A modification to the
      asymmetric model, in which the non-hydrogen-bonded OH intramolecular distance is
      allowed to become shorter while the bonded OH distance becomes longer, improves
      the situation somewhat, but the overall agreement is still unsatisfactory. The
      electric field (E-field) distributions and infrared (IR) spectra are also
      calculated using two established theoretical approaches, which, however, show
      significant discrepancies in their predictions for the asymmetric structural
      models. Both approaches predict the Raman spectrum of the symmetric model fitted
      to the diffraction data to be significantly blueshifted compared to experiment.
      At the moment no water model exists that can equally well describe IR/Raman, x
      ray absorption spectroscopy, and diffraction data.

PMID- 17199359
TI  - Aging correlation functions of the interrupted fractional Fokker-Planck
      propagator.
AB  - The authors explore aging in a general semi-Markov process with arbitrary waiting
      time distributions and discuss the role of trapping phenomenon in glasses in
      determining the waiting time distributions. In certain limits, they obtain a two
      time propagator for the fractional Fokker-Planck equation through coordination,
      but one can generalize the construction to incorporate cutoffs in the aging of
      the system, i.e., the interrupted aging. The construction allows the
      incorporation of cutoffs in the aging of the system, and the exploration of
      signatures of aging effects in systems that eventually achieve equilibrium.
      Cutoffs in aging effects are illustrated for interrupted fractional diffusion in
      a harmonic potential and for the on-time probability of a quantum dot system.

PMID- 17199360
TI  - Time scales and pathways of vibrational energy relaxation in liquid CHBr3 and
      CDBr3.
AB  - Molecular dynamics simulations are used in conjunction with Landau-Teller,
      fluctuating Landau-Teller, and time-dependent perturbation theories to
      investigate energy flow out of various vibrational states of liquid CHBr3 and
      CDBr3. The CH stretch overtone is found to relax with a time scale of about 1 ps
      compared to the 50 ps rate for the fundamental. The relaxation pathways and rates
      for the CD stretch decay in CDBr3 are computed in order to understand the changes
      arising from deuteration. While the computed relaxation rate agrees well with
      experiments, the pathway is found to be more complex than anticipated. In
      addition to the above channels for CH(D) stretch relaxation that involve only the
      hindered translations and rotations of the solvent, routes involving off-resonant
      and resonant excitations of solvent vibrational modes are also examined. Finally,
      the decay of energy from low frequency states to near-lying solute states and
      solvent vibrations are studied.

PMID- 17199361
TI  - Relaxation of the CH stretch in liquid CHBr3: solvent effects and decay rates
      using classical nonequilibrium simulations.
AB  - This article addresses two questions regarding the decay of the CH stretch in
      liquid CHBr3. The first is whether the initial steps of the relaxation primarily
      involve energy redistribution within the excited molecule alone. Gas phase
      quantum mechanical and classical calculations are performed to examine the role
      of the solvent in this process. At the fundamental excitation level, it is found
      that CH stretch decay is, in fact, strongly solvent driven. The second question
      is on the applicability of a fully classical approach to the calculation of CH
      stretch condensed phase decay rates. To this end, nonequilibrium molecular
      dynamics simulations are performed. The results are compared with quantum
      mechanical rates computed previously. The two methods are found to be in fair
      agreement with each other. However, care must be exercised in the interpretation
      of the classical results.

PMID- 17199362
TI  - Current rectification by asymmetric molecules: an ab initio study.
AB  - Current rectification effect in an asymmetric molecule HCOO-C6H4-(CH2)n
      sandwiched between two aluminum electrodes has been studied using an ab initio
      nonequilibrium Green's function method. The conductance of the system decreases
      exponentially with the increasing number n of CH2. The phenomenon of current
      rectification is observed such that a very small current appears at negative bias
      and a sharp negative differential resistance at a critical positive bias when
      n>or=2. The rectification effect arises from the asymmetric structure of the
      molecule and the molecule-electrode couplings. A significant rectification ratio
      of approximately 38 can be achieved when n=5.

PMID- 17199363
TI  - Fitting a free-form scattering length density profile to reflectivity data using
      temperature-proportional quenching.
AB  - A technique for fitting a free-form scattering length density profile to
      reflectivity data via least-squares minimization is presented. The approach
      combines aspects of simulated annealing with a parametrized representation of the
      scattering length density profile. The ability of the algorithm to accurately
      recover the scattering length density profile from arbitrary initial parameter
      values is demonstrated for simulated and experimental data.

PMID- 17199364
TI  - Fluids in porous media. I. A hard sponge model.
AB  - The morphology of many porous materials is spongelike. Despite the abundance of
      such materials, simple models which allow for a theoretical description of these
      materials are still lacking. Here, we propose a hard sponge model which is made
      by digging spherical cavities in a solid continuum. We found an analytical
      expression for describing the interaction potential between fluid particles and
      the spongelike porous matrix. The diagrammatic expansions of different
      correlation functions are derived as well as that of grand potential. We derived
      also the Ornstein-Zernike (OZ) equations for this model. In contrast to Madden
      Glandt model of random porous media [W. G. Madden and E. D. Glandt, J. Stat.
      Phys. 51, 537 (1988)], the OZ equations for a fluid confined in our hard sponge
      model have some similarity to the OZ equations of a three-component fluid
      mixture. We show also how the replica method can be extended to study our sponge
      model and that the same OZ equations can be derived also from the extended
      replica method.

PMID- 17199365
TI  - Hopping times of two hard disks diffusing in a channel.
AB  - A finite difference method was used to solve numerically the multidimensional
      diffusion equation describing the time evolution of two hard disks diffusing in a
      narrow hard channel. The authors extract an estimate for the average time tauhop
      needed for the disks to hop pass each other. For narrow channels near the hopping
      threshold, tauhop diverges and is consistent with the scaling prediction of the
      transition state theory. This provides a much-needed rigorous benchmark to test
      an approximate solution to the diffusion problem.

PMID- 17199367
TI  - Towards atomic site-selective sensitivity in tip-enhanced Raman spectroscopy.
AB  - Depending on each nitrogen atom of adenine molecule to which a silver atom of a
      metallic tip approaches, tip-enhanced near-field Raman spectroscopy may show a
      potential to achieve atomic site-selective detection sensitivity. Molecular
      vibrational calculations show that silver atoms and adenine molecule create
      several isomers generating specific vibrational modes of each isomer that are
      shifted or not observable in isolated adenine molecule itself. Here, the authors
      observe the specific vibrational modes and spectral shifts of isomers
      experimentally and are in good agreement with their calculations.

PMID- 17199366
TI  - Diffusion-limited binding to a site on the wall of a membrane channel.
AB  - The authors develop a theory of diffusion-controlled reactions with a site
      located on the wall of a cylindrical membrane channel that connects two
      reservoirs containing diffusing particles which are trapped by the site at the
      first contact. An expression for the Laplace transform of the rate coefficient,
      kt, is derived assuming that the size of the site is small compared to the
      channel radius. The expression is used to find the stationary value of the rate
      coefficient, kinfinity, as a function of the length and radius of the channel,
      the radius of the site, and its position inside the channel (distances from the
      two ends of the channel) as well as the particle diffusion constants in the bulk
      and in the channel. Their derivation is based on the one-dimensional description
      of the particle motion in the channel, which is generalized to include binding to
      the site into consideration. The validity of the approximate one-dimensional
      description of diffusion and binding was checked by three-dimensional Brownian
      dynamics simulations. They found that the one-dimensional description works
      reasonably well when the size of the site does not exceed 0.2 of the channel
      radius.

PMID- 17199368
TI  - New approach to the kinetics of heterogeneous unary nucleation on liquid aerosols
      of a binary solution.
AB  - The formation of a droplet on a hygroscopic center may occur either in a
      barrierless way via Kohler activation or via nucleation by overcoming a free
      energy barrier. Unlike the former, the latter mechanism of this process has been
      studied very little and only in the framework of the classical nucleation theory
      based on the capillarity approximation whereby a nucleating droplet behaves like
      a bulk liquid. In this paper the authors apply another approach to the kinetics
      of heterogeneous nucleation on liquid binary aerosols, based on a first passage
      time analysis which avoids the concept of surface tension for tiny droplets
      involved in nucleation. Liquid aerosols of a binary solution containing a
      nonvolatile solute are considered. In addition to modeling aerosols formed
      through the deliquescence of solid soluble particles, the considered aerosols
      constitute a rough model of "processed" marine aerosols. The theoretical results
      are illustrated by numerical calculations for the condensation of water vapor on
      binary aqueous aerosols with nonvolatile nondissociating solute molecules using
      Lennard-Jones potentials for the molecular interactions.

PMID- 17199369
TI  - Determination of rotary diffusivity of poly(n-propyl isocyanate) by molecular
      dynamics.
AB  - The rotational dynamics of a nondilute solution of the rodlike polymer poly(n
      propyl isocyanate) (PPIC) has been studied on an atomistic model by means of a
      large-scale classical molecular dynamics investigation. The rotary diffusivity of
      PPIC in toluene solution has been determined from the Einsteinian diffusion
      regime of the end-to-end vector on the surface of the unit sphere and has been
      found to be Dr=10.5x10(5)(+/-2.7) s-1, which falls in the range of the
      experimental data available. A comparison of molecular dynamics predictions with
      theoretical and perturbation expansion predictions has also been performed.

PMID- 17199370
TI  - Unified model of association-induced lower critical solution temperature phase
      separation and its application to solutions of telechelic poly(ethylene oxide)
      and of telechelic poly(N-isopropylacrylamide) in water.
AB  - The authors present a model describing the coexistence of hydrophobic association
      and phase separation with lower critical solution temperature (LCST) in aqueous
      solutions of polymers carrying short hydrophobic chains at both chain ends
      (telechelic associating polymers). The LCST of these solutions is found to
      decrease along the sol/gel transition curve as a result of both end-chain
      association (association-induced phase separation) and direct hydrophobic
      interaction of the end chains with water. The authors relate the magnitude of the
      LCST decrease to a hydration cooperativity parameter sigma. The LCST decreases
      substantially (approximately 100 K) in the case of random hydration (sigma=1),
      whereas only a small shift (approximately 5-10 K) occurs in the case of
      cooperative hydration (sigma=0.3). The molecular weight dependence of the LCST
      drop is studied in detail in each case. The results are compared with
      experimental observations of the cloud points of telechelic poly(ethylene oxide)
      solutions, in which random hydration predominates, and of telechelic poly(N
      isopropylacrylamide) solutions, in which cooperative hydration prevails.

PMID- 17199371
TI  - Comment on "Legendre-transform functionals for spin-density-functional theory"
      [J. Chem. Phys. 124, 224108 (2006)].

PMID- 17199374
TI  - Splash and anti-splash: observation and design.

PMID- 17199375
TI  - Edge of chaos in pipe flow.

PMID- 17199376
TI  - Crowd synchrony on the London Millennium Bridge.

PMID- 17199377
TI  - Driven inertial waves in spherical Couette flow.

PMID- 17199378
TI  - Community structure in the U.S. House of Representatives.

PMID- 17199379
TI  - Anomalous transport fluctuations in a model of irregular media.
AB  - We consider a diffusion model with stochastic porosity for which the average
      solution exhibits an abnormal transport. In this paper we investigate the
      relation of such an anomalous diffusive property of the mean value with the
      behavior of the solution corresponding to each realization of the stochastic
      porosity. Such a solution will correspond to the actual measurements in an
      experiment made on a particular tube. The most relevant result of our work is
      that, although the concentration corresponding to each realization diffuses
      normally for large times, it experiments on large deviations from the mean value
      during intermediate times.

PMID- 17199380
TI  - Variance estimators for the Lempel-Ziv entropy rate estimator.
AB  - Lempel and Ziv's 1976 algorithm provides an easy-to-compute way to automatically
      estimate the entropy rate for symbolic time series, requiring no free parameters.
      Here we derive an analytical variance estimate for the Lempel-Ziv entropy rate
      estimator that is easily computable from observations with negligible extra
      effort beyond the entropy rate itself, and compare to another procedure, a time
      series-based bootstrap method. These provide a justified "error bar" quantifying
      the size of expected fluctuations on the estimate itself, given by the single
      time series of symbols.

PMID- 17199381
TI  - Evolution of Benjamin-Ono solitons in the presence of weak Zakharov-Kutznetsov
      lateral dispersion.
AB  - The effect of weak lateral dispersion of Zakharov-Kutznetsov-type on a Benjamin
      Ono solitary wave is studied both asymptotically and numerically. The asymptotic
      solution is based on an approximate variational solution for the solitary wave,
      which is then modulated in time through the use of conservation equations. The
      effect of the dispersive radiation shed as the solitary wave evolves is also
      included in the modulation equations. It is found that the weak lateral
      dispersion produces a strongly anisotropic, stable solitary wave which decays
      algebraically in the direction of propagation, as for the Benjamin-Ono solitary
      wave, and exponentially in the transverse direction. Moreover, it is found that
      initial conditions with amplitude above a threshold evolve into solitary waves,
      while those with amplitude below the threshold evolve as lumps for a short time,
      then merge into radiation. The modulation equations are found to give a
      quantitatively accurate description of the evolution of an initial condition into
      an anisotropic solitary wave. The existence of stable solitary waves is in
      contrast to previous studies of Benjamin-Ono-type equations subject to the
      stronger Kadomstev-Petviashvili or Benjamin-Ono-type lateral dispersion, for
      which the solitary waves either decay or collapse. The present study then
      completes the catalog of possible behaviors under lateral dispersion.

PMID- 17199382
TI  - Merger of coherent structures in time-periodic viscous flows.
AB  - Inertia-induced changes in transport properties of an incompressible viscous time
      periodic flow are studied in terms of the topological properties of volume
      preserving maps. In the noninertial limit, the flow admits one constant of motion
      and thus relates to a so-called one-action map. However, the invariant surfaces
      corresponding to the constant of motion are topologically equivalent to spheres
      rather than the common case of tori. This has fundamental ramifications for the
      effect of inertia and leads to a new kind of response scenario: resonance-induced
      merger of coherent structures.

PMID- 17199383
TI  - Long-term memory contribution as applied to the motion of discrete dynamical
      systems.
AB  - We consider the evolution of logistic maps under long-term memory. The memory
      effects are characterized by one parameter, alpha. If it equals to zero, any
      memory is absent. This leads to the ordinary discrete dynamical systems. For
      alpha=1 the memory becomes full, and each subsequent state of the corresponding
      discrete system accumulates all past states with the same weight just as the
      ordinary integral of first order does in the continuous space. The case with
      0<alpha<1 has the long-term memory effects. The characteristic features are also
      observed for the fractional integral depending on time, and the parameter alpha
      is equivalent to the order index of the fractional integral. We study the
      evolution of the bifurcation diagram among alpha=0 and alpha=0.15. The main
      result of this work is that the long-term memory effects make difficulties for
      developing the chaos motion in such logistic maps. The parameter alpha resembles
      a governing parameter for the bifurcation diagram. For alpha>0.15 the memory
      effects win over chaos.

PMID- 17199384
TI  - Propagation velocities of chemical reaction fronts advected by Poiseuille flow.
AB  - Poiseuille flow between parallel plates advects chemical reaction fronts,
      distorting them and altering their propagation velocities. Analytical solutions
      of the cubic reaction-diffusion-advection equation resolve the chemical
      concentration for narrow gaps, wide gaps, and small-amplitude flow. Numerical
      solutions supply a general description for fluid flow in the direction of
      propagation of the chemical reaction front, and for flow in the opposite
      direction. Empirical relations for the velocity agree with numerical solutions to
      within a few percent, and agree exactly with the analytical limits. Applications
      to nonlinear fingering are discussed.

PMID- 17199385
TI  - Frequency-selective response of FitzHugh-Nagumo neuron networks via changing
      random edges.
AB  - We consider a network of FitzHugh-Nagumo neurons; each neuron is subjected to a
      subthreshold periodic signal and independent Gaussian white noise. The firing
      pattern of the mean field changes from an internal-scale dominant pattern to an
      external-scale dominant one when more and more edges are added into the network.
      We find numerically that (a) this transition is more sensitive to random edges
      than to regular edges, and (b) there is a saturation length for random edges
      beyond which the transition is no longer sharpened. The influence of network size
      is also investigated.

PMID- 17199386
TI  - Nonergodicity of the motion in three-dimensional steep repelling dispersing
      potentials.
AB  - It is demonstrated numerically that smooth three degrees of freedom Hamiltonian
      systems that are arbitrarily close to three-dimensional strictly dispersing
      billiards (Sinai billiards) have islands of effective stability, and hence are
      nonergodic. The mechanism for creating the islands is corners of the billiards
      domain.

PMID- 17199387
TI  - Modeling global vector fields of chaotic systems from noisy time series with the
      aid of structure-selection techniques.
AB  - We address the problem of reconstructing a set of nonlinear differential
      equations from chaotic time series. A method that combines the implicit Adams
      integration and the structure-selection technique of an error reduction ratio is
      proposed for system identification and corresponding parameter estimation of the
      model. The structure-selection technique identifies the significant terms from a
      pool of candidates of functional basis and determines the optimal model through
      orthogonal characteristics on data. The technique with the Adams integration
      algorithm makes the reconstruction available to data sampled with large time
      intervals. Numerical experiment on Lorenz and Rossler systems shows that the
      proposed strategy is effective in global vector field reconstruction from noisy
      time series.

PMID- 17199388
TI  - Coexistence of inertial competitors in chaotic flows.
AB  - We investigate the dynamics of inertial particles immersed in open chaotic flows.
      We consider the generic problem of competition between different species, e.g.,
      phytoplankton populations in oceans. The strong influence from inertial effects
      is shown to result in the persistence of different species even in cases when the
      passively advected species cannot coexist. Multispecies coexistence in the ocean
      can be explained by the fact that the unstable manifold is different for each
      advected competitor of different size.

PMID- 17199389
TI  - On-off intermittency in time series of spontaneous paroxysmal activity in rats
      with genetic absence epilepsy.
AB  - In the present paper we consider the on-off intermittency phenomena observed in
      time series of spontaneous paroxysmal activity in rats with genetic absence
      epilepsy. The method to register and analyze the electroencephalogram with the
      help of continuous wavelet transform is also suggested.

PMID- 17199390
TI  - Synchronizabilities of networks: a new index.
AB  - The random matrix theory is used to bridge the network structures and the
      dynamical processes defined on them. We propose a possible dynamical mechanism
      for the enhancement effect of network structures on synchronization processes,
      based upon which a dynamic-based index of the synchronizability is introduced in
      the present paper.

PMID- 17199391
TI  - Synchronization by dynamical relaying in electronic circuit arrays.
AB  - We experimentally study the synchronization of two chaotic electronic circuits
      whose dynamics is relayed by a third parameter-matched circuit, to which they are
      coupled bidirectionally in a linear chain configuration. In a wide range of
      operating parameters, this setup leads to synchronization between the outer
      circuits, while the relaying element remains unsynchronized. The specifics of the
      synchronization differ with the coupling level: for low couplings a state of
      intermittent synchronization between the outer circuits coexists with one of
      antiphase synchronization. Synchronization becomes in phase for moderate
      couplings, and for strong coupling identical synchronization is observed between
      the outer elements, which are themselves synchronized in a generalized way with
      the relaying element. In the latter situation, the middle element displays a
      triple-scroll attractor that is not possible to obtain when the chaotic
      oscillator is isolated.

PMID- 17199392
TI  - Entropy, thermostats, and chaotic hypothesis.
AB  - The chaotic hypothesis is proposed as a basic for a general theory of
      nonequilibrium stationary states.

PMID- 17199393
TI  - On parameter estimation of chaotic systems via symbolic time-series analysis.
AB  - Symbolic time-series analysis is used for estimating the parameters of chaotic
      systems. It is assumed that a "target model" (i.e., a discrete- or continuous
      time description of the data-generating mechanism) is available, but with unknown
      parameters. A time series, i.e., a noisy, finite sequence of a measured (output)
      variable, is given. The proposed method first prescribes to symbolize the time
      series, i.e., to transform it into a sequence of symbols, from which the
      statistics of symbols are readily derived. Then, a symbolic model (in the form of
      a Markov chain) is derived from the data. It allows one to predict, in a
      probabilistic fashion, the time evolution of the symbol sequence. The unknown
      parameters are derived by matching either the statistics of symbols, or the
      symbolic prediction derived from data, with those generated by the (parametrized)
      target model. Three examples of application (the Henon map, a population model,
      and the Duffing system) prove that satisfactory results can be obtained even with
      short time series.

PMID- 17199394
TI  - Delay-coordinates embeddings as a data mining tool for denoising speech signals.
AB  - In this paper, we utilize techniques from the theory of nonlinear dynamical
      systems to define a notion of embedding estimators. More specifically, we use
      delay-coordinates embeddings of sets of coefficients of the measured signal (in
      some chosen frame) as a data mining tool to separate structures that are likely
      to be generated by signals belonging to some predetermined data set. We implement
      the embedding estimator in a windowed Fourier frame, and we apply it to speech
      signals heavily corrupted by white noise. Our experimental work suggests that,
      after training on the data sets of interest, these estimators perform well for a
      variety of white noise processes and noise intensity levels.

PMID- 17199395
TI  - The variant of post-Newtonian mechanics with generalized fractional derivatives.
AB  - In this article, we investigate mathematically the variant of post-Newtonian
      mechanics using generalized fractional derivatives. The relativistic-covariant
      generalization of the classical equations for gravitational field is studied. The
      equations (i) match the weak Newtonian limit on the moderate scales and (ii)
      deliver a potential higher than Newtonian on certain large-distance
      characteristic scales. The perturbation of the gravitational field results in the
      tiny secular perihelion shift and exhibits some unusual effects on large scales.
      The general representation of the solution for the fractional wave equation is
      given in the form of retarded potentials. The solutions for the Riesz wave
      equation and classical wave equation are clearly distinctive in an important
      sense. The hypothetical gravitational Riesz wave demonstrates the space diffusion
      of the wave at the scales of metric constant. The diffusion leads to the blur of
      the peak and disruption of the sharp wave front. This contrasts with the solution
      of the D'Alembert classical wave equation, which obeys the Huygens principle and
      does not diffuse.

PMID- 17199396
TI  - A new chaotic communication scheme based on adaptive synchronization.
AB  - A new chaotic communication scheme using adaptive synchronization technique of
      two unified chaotic systems is proposed. Different from the existing secure
      communication methods, the transmitted signal is modulated into the parameter of
      chaotic systems. The adaptive synchronization technique is used to synchronize
      two identical chaotic systems embedded in the transmitter and the receiver. It is
      assumed that the parameter of the receiver system is unknown. Based on the
      Lyapunov stability theory, an adaptive control law is derived to make the states
      of two identical unified chaotic systems with unknown system parameters
      asymptotically synchronized; thus the parameter of the receiver system is
      identified. Then the recovery of the original information signal in the receiver
      is successfully achieved on the basis of the estimated parameter. It is noticed
      that the time required for recovering the information signal and the accuracy of
      the recovered signal very sensitively depends on the frequency of the information
      signal. Numerical results have verified the effectiveness of the proposed scheme.

PMID- 17199397
TI  - Shilnikov homoclinic orbit bifurcations in the Chua's circuit.
AB  - We analytically describe the complex scenario of homoclinic bifurcations in the
      Chua's circuit. We obtain a general scaling law that gives the ratio between
      bifurcation parameters of different nearby homoclinic orbits. As an application
      of this theoretical approach, we estimate the number of higher order subsidiary
      homoclinic orbits that appear between two consecutive lower order subsidiary
      orbits. Our analytical finds might be valid for a large class of dynamical
      systems and are numerically confirmed in the parameter space of the Chua's
      circuit.

PMID- 17199398
TI  - Design of multidirectional multiscroll chaotic attractors based on fractional
      differential systems via switching control.
AB  - This paper proposes a saturated function series approach for generating
      multiscroll chaotic attractors from the fractional differential systems,
      including one-directional (1-D) n-scroll, two-directional (2-D) nxm-grid scroll,
      and three-directional (3-D) nxmxl-grid scroll chaotic attractors. Our theoretical
      analysis shows that all scrolls are located around the equilibria corresponding
      to the saturated plateaus of the saturated function series on a line in the 1-D
      case, a plane in the 2-D case, and a three-dimensional space in the 3-D case,
      respectively. In particular, each saturated plateau corresponds to a unique
      equilibrium and its unique scroll of the whole attractor. In addition, the number
      of scrolls is equal to the number of saturated plateaus in the saturated function
      series. Finally, some underlying dynamical mechanisms are then further
      investigated for the fractional differential multiscroll systems.

PMID- 17199399
TI  - Measuring asymmetric temporal interdependencies in simulated and biological
      networks.
AB  - We use a newly developed metric to characterize asymmetric temporal
      interdependencies in networks of coupled dynamical elements. We studied the
      formation of temporal ordering in a system of coupled Rossler oscillators for
      different connectivity ratios and network topologies and also applied the metric
      to investigate the functional structure of a biological network (cerebral ganglia
      of Helix snail). In the former example we show how the local ordering evolves to
      the global one as a function of structural parameters of the network, while in
      the latter we show spontaneous emergence of functional interdependence between
      two groups of electrodes.

PMID- 17199400
TI  - Theoretical and experimental studies of parameter estimation based on chaos
      feedback synchronization.
AB  - In this paper, we perform theoretical and experimental studies of parameter
      estimation based on chaos feedback synchronization. The Chua chaotic system is
      applied as the original system, and its time series of a single variable is
      applied as a feedback variable to drive a simulative system. The simplex method
      is employed to minimize the synchronization error in the simulative system to
      iteratively approach the original system parameters. Furthermore, the effects of
      feedback function, feedback weight, and noise are investigated. The parameter
      estimation method based on feedback synchronization shows its robustness to noise
      perturbation. Finally, the circuit experiment of parameter estimation is
      implemented in order to examine its practical applicability. The original Chua
      circuit parameters can be well approached from its recorded time series of a
      single variable. The results show the parameter estimation method based on
      feedback synchronization may be capable of estimating real system parameters from
      a chaotic time series.

PMID- 17199401
TI  - On passage through resonances in volume-preserving systems.
AB  - Resonance processes are common phenomena in multiscale (slow-fast) systems. In
      the present paper we consider capture into resonance and scattering on resonance
      in 3D volume-preserving multiscale systems. We propose a general theory of those
      processes and apply it to a class of kinematic models inspired by viscous Taylor
      Couette flows between two counter-rotating cylinders. We describe the phenomena
      during a single passage through resonance and show that multiple passages lead to
      the chaotic advection and mixing. We calculate the width of the mixing domain and
      estimate a characteristic time of mixing. We show that the resultant mixing can
      be described using a diffusion equation with a diffusion coefficient depending on
      the averaged effect of the passages through resonances.

PMID- 17199402
TI  - Unusual pulsating states in hydrocarbon-oxygen premixed flames.
AB  - An unusual type of pulsating state has been observed using a new ignition
      protocol for heavy hydrocarbon-oxygen premixed flames on a circular porous plug
      burner. The shape and motion of these states are quasicircular, luminous,
      pulsating regions of M (M=1, 2, 3, or 4) lobes that increase in size as the flame
      propagates outward. As the lobes expand, they break apart near their midpoints
      and form counterpropagating spiral-like arms. These spiral arms rotate, "collide"
      with arms generated by adjacent lobes, and are extinguished. We will describe the
      unusual characteristics of the dynamics of these states.

PMID- 17199403
TI  - Equilibriumizing all food chain chaos through reproductive efficiency.
AB  - The intraspecific interference of a top-predator is incorporated into a classical
      mathematical model for three-trophic food chains. All chaos types known to the
      classical model are shown to exist for this comprehensive model. It is further
      demonstrated that if the top-predator reproduces at high efficiency, then all
      chaotic dynamics will change to a stable coexisting equilibrium, a novel property
      not found in the classical model. This finding gives a mechanistic explanation to
      the question of why food chain chaos is rare in the field. It also suggests that
      high reproductive efficiency of top-predators tends to stabilize food chains.

PMID- 17199404
TI  - Bistable phase control via rocking in a nonlinear electronic oscillator.
AB  - We experimentally demonstrate the effective rocking [de Valcarcel and Staliunas,
      Phys. Rev. E 67, 026604 (2003)] of a nonlinear electronic circuit operating in a
      periodic regime. Namely, we show that by driving a Chua circuit with a periodic
      signal, whose phase alternates (also periodically) in time, we lock the
      oscillation frequency of the circuit to that of the driving signal, and its phase
      to one of two possible values shifted by pi, and lying between the alternating
      phases of the input signal. In this way, we show that a rocked nonlinear
      oscillator displays phase bistability. We interpret the experimental results via
      a theoretical analysis of rocking on a simple oscillator model, based on a normal
      form description (complex Landau equation) of the rocked Hopf bifurcation.

PMID- 17199405
TI  - Comment on "Identification of low order manifolds: validating the algorithm of
      Maas and Pope" [Chaos 9, 108-123 (1999)].
AB  - It is claimed by Rhodes, Morari, and Wiggins [Chaos 9, 108-123 (1999)] that the
      projection algorithm of Maas and Pope [Combust. Flame 88, 239-264 (1992)]
      identifies the slow invariant manifold of a system of ordinary differential
      equations with time-scale separation. A transformation to Fenichel normal form
      serves as a tool to prove this statement. Furthermore, Rhodes, Morari, and
      Wiggins [Chaos 9, 108-123 (1999)] conjectured that away from a slow manifold, the
      criterion of Maas and Pope will never be fulfilled. We present two examples that
      refute the assertions of Rhodes, Morari, and Wiggins. In the first example, the
      algorithm of Maas and Pope leads to a manifold that is not invariant but close to
      a slow invariant manifold. The claim of Rhodes, Morari, and Wiggins that the Maas
      and Pope projection algorithm is invariant under a coordinate transformation to
      Fenichel normal form is shown to be not correct in this case. In the second
      example, the projection algorithm of Maas and Pope leads to a manifold that lies
      in a region where no slow manifold exists at all. This rejects the conjecture of
      Rhodes, Morari, and Wiggins mentioned above.

PMID- 17199407
TI  - Unacceptably high mortality related to measles epidemics in Niger, Nigeria, and
      Chad.
AB  - BACKGROUND: Despite the comprehensive World Health Organization (WHO)/United
      Nations Children's Fund (UNICEF) measles mortality-reduction strategy and the
      Measles Initiative, a partnership of international organizations supporting
      measles mortality reduction in Africa, certain high-burden countries continue to
      face recurrent epidemics. To our knowledge, few recent studies have documented
      measles mortality in sub-Saharan Africa. The objective of our study was to
      investigate measles mortality in three recent epidemics in Niamey (Niger),
      N'Djamena (Chad), and Adamawa State (Nigeria). METHODS AND FINDINGS: We conducted
      three exhaustive household retrospective mortality surveys in one neighbourhood
      of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n =
      26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District,
      Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed
      population in each of the respective areas. Study populations included all
      persons resident for at least 2 wk prior to the study, a duration encompassing
      the measles incubation period. Heads of households provided information on
      measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking
      behaviour during the epidemic. Measles cases and deaths were ascertained using
      standard WHO surveillance-case definitions. Our main outcome measures were
      measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and
      descriptions of measles complications and health-seeking behaviour. Measles ARs
      were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2%
      in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%,
      and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites,
      more than half of measles cases in children aged under 5 y experienced acute
      respiratory infection and/or diarrhoea in the 30 d following rash onset. Of
      measles cases, it was reported that 85.7% (979/1,142) of patients visited a
      health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in
      Moursal, and 52.8% (603/1,142) in Dong District. CONCLUSIONS: Children in these
      countries still face unacceptably high mortality from a completely preventable
      disease. While the successes of measles mortality-reduction strategies and
      progress observed in measles control in other countries of the region are
      laudable and evident, they should not overshadow the need for intensive efforts
      in countries that have just begun implementation of the WHO/UNICEF comprehensive
      strategy.

PMID- 17199408
TI  - Epidemiology of tuberculosis in a high HIV prevalence population provided with
      enhanced diagnosis of symptomatic disease.
AB  - BACKGROUND: Directly observed treatment short course (DOTS), the global control
      strategy aimed at controlling tuberculosis (TB) transmission through prompt
      diagnosis of symptomatic smear-positive disease, has failed to prevent rising
      tuberculosis incidence rates in Africa brought about by the HIV epidemic.
      However, rising incidence does not necessarily imply failure to control
      tuberculosis transmission, which is primarily driven by prevalent infectious
      disease. We investigated the epidemiology of prevalent and incident TB in a high
      HIV prevalence population provided with enhanced primary health care. METHODS AND
      FINDINGS: Twenty-two businesses in Harare, Zimbabwe, were provided with free
      smear- and culture-based investigation of TB symptoms through occupational
      clinics. Anonymised HIV tests were requested from all employees. After 2 y of
      follow-up for incident TB, a culture-based survey for undiagnosed prevalent TB
      was conducted. A total of 6,440 of 7,478 eligible employees participated. HIV
      prevalence was 19%. For HIV-positive and -negative participants, the incidence of
      culture-positive tuberculosis was 25.3 and 1.3 per 1,000 person-years,
      respectively (adjusted incidence rate ratio = 18.8; 95% confidence interval [CI]
      = 10.3 to 34.5: population attributable fraction = 78%), and point prevalence
      after 2 y was 5.7 and 2.6 per 1,000 population (adjusted odds ratio = 1.7; 95% CI
      = 0.5 to 6.8: population attributable fraction = 14%). Most patients with
      prevalent culture-positive TB had subclinical disease when first detected.
      CONCLUSIONS: Strategies based on prompt investigation of TB symptoms, such as
      DOTS, may be an effective way of controlling prevalent TB in high HIV prevalence
      populations. This may translate into effective control of TB transmission despite
      high TB incidence rates and a period of subclinical infectiousness in some
      patients.

PMID- 17199409
TI  - Measles still has a devastating impact in unvaccinated populations.

PMID- 17199413
TI  - Density and morphologic features of primary epidermal laminae in the feet of
      three-year-old racing Quarter Horses.
AB  - OBJECTIVE: To quantify the density of primary epidermal laminae (PELs) around the
      solar circumference and evaluate the relationship between regional PEL density
      and hoof capsule morphology in horses. SAMPLE POPULATION: Forefeet from nine 3
      year-old Quarter Horse cadavers. PROCEDURES: Data pertaining to gross features of
      hoof morphology and PEL variables, including number, density, and distribution
      patterns around the perimeter of the hoof wall and number of bar PELs, were
      collected. Tissues of the laminar junction were examined histologically. RESULTS:
      No significant differences were found between left and right forefeet with
      respect to gross hoof morphologic measurements. Mean +/- SD number of PELs,
      including those at the bars of the hoof, was 551 +/- 30. Primary epidermal
      laminar density in the toe was significantly higher, compared with that in the
      quarter and heel regions, and was higher on the lateral aspect of the foot,
      compared with the medial aspect. Feet were significantly wider on the lateral
      aspect of the foot, compared with the medial aspect, as measured across the
      widest point of the solar surface. Histologic examination revealed atypical
      laminar morphology at the toe. CONCLUSIONS AND CLINICAL RELEVANCE: Variations
      were detected in PEL density and morphology around the solar circumference of
      hooves from 3-year-old racing Quarter Horses. A better understanding of
      relationships between laminar density, laminar morphology, and gross morphology
      of the hoof capsule in different populations of horses may aid practitioners in
      diagnosis and treatment of disease involving the hoof wall in horses.

PMID- 17199410
TI  - Timing and sequence of brain activity in top-down control of visual-spatial
      attention.
AB  - Recent brain imaging studies using functional magnetic resonance imaging (fMRI)
      have implicated a frontal-parietal network in the top-down control of attention.
      However, little is known about the timing and sequence of activations within this
      network. To investigate these timing questions, we used event-related electrical
      brain potentials (ERPs) and a specially designed visual-spatial attentional
      cueing paradigm, which were applied as part of a multi-methodological approach
      that included a closely corresponding event-related fMRI study using an identical
      paradigm. In the first 400 ms post cue, attention-directing and control cues
      elicited similar general cue-processing activity, corresponding to the more
      lateral subregions of the frontal-parietal network identified with the fMRI.
      Following this, the attention-directing cues elicited a sustained negative
      polarity brain wave that was absent for control cues. This activity could be
      linked to the more medial frontal-parietal subregions similarly identified in the
      fMRI as specifically involved in attentional orienting. Critically, both the
      scalp ERPs and the fMRI-seeded source modeling for this orienting-related
      activity indicated an earlier onset of frontal versus parietal contribution (
      approximately 400 versus approximately 700 ms). This was then followed (
      approximately 800-900 ms) by pretarget biasing activity in the region-specific
      visual-sensory occipital cortex. These results indicate an activation sequence of
      key components of the attentional-control brain network, providing insight into
      their functional roles. More specifically, these results suggest that voluntary
      attentional orienting is initiated by medial portions of frontal cortex, which
      then recruit medial parietal areas. Together, these areas then implement biasing
      of region-specific visual-sensory cortex to facilitate the processing of upcoming
      visual stimuli.

PMID- 17199414
TI  - Anesthesia induced by administration of xylazine hydrochloride alone or in
      combination with ketamine hydrochloride and reversal by administration of
      yohimbine hydrochloride in captive Axis deer (Axis axis).
AB  - OBJECTIVE: To determine the anesthetic dose and cardiopulmonary effects of
      xylazine hydrochloride when used alone or in combination with ketamine
      hydrochloride and evaluate the efficacy of yohimbine hydrochloride to reverse
      anesthetic effects in captive Axis deer. ANIMALS: 35 adult (10 males and 25
      females) Axis deer (Axis axis). PROCEDURES: All deer were anesthetized by IM
      administration of xylazine (3.5 mg/kg; experiment 1), a combination of ketamine
      and xylazine (1.25 and 1.5 mg/kg, respectively; experiment 2), or another
      combination of ketamine and xylazine (2.5 and 0.5 mg/kg, respectively; experiment
      3). In addition, female deer were also anesthetized by IM administration of a
      third combination of ketamine and xylazine (1.5 and 1 mg/kg, respectively;
      experiment 4). Ten to 40 minutes after induction, anesthesia was reversed by IV
      administration of yohimbine (5, 8, or 10 mg). RESULTS: In male deer, experiment 3
      yielded the most rapid induction of anesthesia. In females, experiment 4 yielded
      the best induction of anesthesia without adverse effects. All doses of yohimbine
      reversed anesthesia. Duration of anesthesia before administration of yohimbine
      had no effect on recovery time. CONCLUSIONS AND CLINICAL RELEVANCE: A combination
      of ketamine and xylazine can be used to induce anesthesia in Axis deer.
      Furthermore, anesthetic effects can be reversed by administration of yohimbine.

PMID- 17199415
TI  - Pharmacokinetics and pharmacodynamics of morphine in llamas.
AB  - OBJECTIVE: To assess the pharmacokinetics and pharmacodynamics of morphine in
      llamas. ANIMALS: 6 healthy adult llamas. PROCEDURES: Llamas received morphine
      sulfate in a randomized crossover design. In phase 1, they received IV or IM
      administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they
      received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma
      morphine and morphine-6-glucuronide concentrations were determined by validated
      methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia
      were assessed and compared with plasma concentrations by regression analysis.
      RESULTS: Total body clearance was similar between IV administration of morphine
      sulfate at 0.25 and 0.5 mg/kg (mean +/- SD, 25.3 +/- 6.9 mL/min/kg and 27.3 +/-
      5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses.
      Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 +/-
      30%. Body temperature and sedation increased as the dose of morphine administered
      increased. Heart rate was unaffected by varying doses. Respiratory rate decreased
      as dose increased. Analgesia was difficult to assess as a result of high
      individual variability. Intravenous administration of morphine at 0.25 mg/kg
      provided the most consistent increase in tolerance to electric stimulation.
      Pharmacodynamic modeling revealed a sigmoidal relationship between plasma
      concentration and sedation score. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine
      was characterized by a large apparent volume of distribution and high systemic
      clearance in llamas. A prolonged half-life was observed with IM injection.
      Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is
      suggested for further study.

PMID- 17199416
TI  - Quantitative genetics of secondary hip joint osteoarthritis in a Labrador
      Retriever-Greyhound pedigree.
AB  - OBJECTIVE: To evaluate the quantitative inheritance of secondary hip joint
      osteoarthritis in a canine pedigree. ANIMALS: 137 Labrador Retrievers,
      Greyhounds, and mixed-breed dogs. PROCEDURES: Necropsy scores ranging from 0 to 4
      were obtained for each hip joint. Seven unaffected Greyhounds with normal hip
      joint conformation were also used for genetic modeling, but were not euthanized.
      Sixty-six male and 71 female dogs were allocated to 2 groups (< or = 12 months of
      age and > 12 months of age). Statistical models were developed to establish the
      inheritance pattern of hip joint osteoarthritis that developed secondary to hip
      dysplasia. RESULTS: 62 dogs had evidence of osteoarthritis in a hip joint, and 75
      had no evidence of osteoarthritis. After sex was adjusted for, the necropsy score
      was found to be inherited additively but without dominance. Each Labrador
      Retriever allele increased the necropsy score by 0.7 to 0.9 points, compared with
      the Greyhound allele, and male sex increased the necropsy score 0.74 over female
      sex. Approximately 10% of the variation in necropsy score was attributable to the
      litter of puppies' origin. CONCLUSIONS AND CLINICAL RELEVANCE: Because secondary
      hip joint osteoarthritis is inherited additively, selection pressure could be
      applied to reduce its incidence. Similar statistical models can be used in
      linkage and association mapping to detect the genes in the underlying
      quantitative trait loci that contribute to hip joint osteoarthritis.

PMID- 17199417
TI  - Prospective screening for occult cardiomyopathy in dogs by measurement of plasma
      atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I
      concentrations.
AB  - OBJECTIVE: To evaluate the use of measuring plasma concentrations of atrial
      natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin
      I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). ANIMALS: 118
      client-owned dogs. PROCEDURES: Dogs were prospectively examined by use of ECG;
      echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult
      DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions
      and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of
      assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect
      dogs with occult DCM were determined. RESULTS: Occult DCM was diagnosed in 21
      dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and
      specificity of 61.9% for identifying dogs with occult DCM. In contrast,
      concentrations of ANP and cTnI had relatively low predictive values. CONCLUSIONS
      AND CLINICAL RELEVANCE: Blood-based screening for occult DCM in dogs can be
      accomplished by use of a BNP assay. Additional studies should be performed to
      optimize this method of screening dogs to detect occult DCM.

PMID- 17199418
TI  - Efficacy of maropitant for treatment and prevention of emesis caused by
      intravenous infusion of cisplatin in dogs.
AB  - OBJECTIVE: To evaluate the efficacy of maropitant, a novel neurokinin-1 receptor
      antagonist, to treat and prevent emesis caused by IV infusion of a
      chemotherapeutic dose of cisplatin (70 mg/m(2)) in dogs. ANIMALS: 64 healthy 6
      month-old Beagles (32 males and 32 females). PROCEDURES: To evaluate the effect
      of maropitant on ongoing emesis, 24 dogs were randomized to 2 treatment groups
      (12 dogs each). Saline (0.9% NaCl) solution or maropitant (1 mg/kg) was
      administered once by SC injection immediately following the first emetic event
      after cisplatin infusion. Dogs were assessed for emesis for 6 hours after
      initiation of cisplatin infusion. To evaluate the use of maropitant for the
      prevention of emesis, 40 dogs were randomized to 4 treatment groups (10 dogs
      each). Placebo or maropitant (1, 2, or 3 mg/kg) was administered PO as a tablet.
      Cisplatin infusion was initiated at 19 hours after treatment, and dogs were
      assessed for emesis for 6 hours. RESULTS: No treatment-related adverse events
      were observed in either study. For the treatment of ongoing emesis, significantly
      fewer emetic events were observed for maropitant-treated dogs, compared with
      placebo-treated dogs (mean, 5.2 vs 15.8), and the mean time to cessation of
      emesis was significantly shorter (0.65 vs 1.65 hours). In the prevention of
      emesis, maropitant-treated dogs had significantly fewer emetic events (means,
      2.7, 1.1, and 0.5 for maropitant at 1, 2, and 3 mg/kg, respectively), compared
      with placebo-treated dogs (mean, 20.3). CONCLUSIONS AND CLINICAL RELEVANCE:
      Results suggest that maropitant is safe and effective in the treatment and
      prevention of cisplatin-induced emesis in dogs.

PMID- 17199419
TI  - Serum concentrations of adiponectin and characterization of adiponectin protein
      complexes in dogs.
AB  - OBJECTIVE: To assess serum concentrations of adiponectin and characterize
      adiponectin protein complexes in healthy dogs. ANIMALS: 11 healthy dogs.
      PROCEDURES: Sera collected from 10 dogs were evaluated via velocity sedimentation
      and ultracentrifugation, SDS-PAGE, western immunoblotting, and radioimmunoassay.
      Visceral adipose tissue (approx 90 g) was collected from the falciform ligament
      of a healthy dog undergoing elective ovariohysterectomy, and adiponectin gene
      expression was assessed via a real-time PCR procedure. RESULTS: Adiponectin gene
      expression was detected in visceral adipose tissue. Serum adiponectin
      concentrations ranged from 0.85 to 1.5 microg/mL (mean concentration, 1.22
      microg/mL). In canine serum, adiponectin was present as a multimer, consisting of
      a low-molecular-weight complex (180 kd); as 3 (180-, 90-, and 60-kd) complexes
      under denaturing conditions; as 2 (90- and 60-kd) complexes under reducing
      conditions; and as a dimer, a monomer, and globular head region (60, 30, and 28
      kd, respectively) under reducing-denaturing conditions. It is likely that
      adiponectin also circulates as a high-molecular-weight (360- to 540-kd) complex
      in canine serum, but resolution of this complex was not possible via SDS-PAGE.
      CONCLUSIONS AND CLINICAL RELEVANCE: After exposure to identical experimental
      conditions, adiponectin protein complexes in canine serum were similar to those
      detected in human and rodent sera. Circulating adiponectin concentrations in
      canine serum were slightly lower than concentrations in human serum. Adiponectin
      gene expression was identified in canine visceral adipose tissue. Results suggest
      that adiponectin could be used as an early clinical marker for metabolic
      derangements, including obesity, insulin resistance, and diabetes mellitus in
      dogs.

PMID- 17199420
TI  - Evaluation of fecal samples from mares as a source of Rhodococcus equi for their
      foals by use of quantitative bacteriologic culture and colony immunoblot
      analyses.
AB  - OBJECTIVE: To determine whether mares are a clinically important source of
      Rhodococcus equi for their foals. SAMPLE POPULATION: 171 mares and 171 foals from
      a farm in Kentucky (evaluated during 2004 and 2005). PROCEDURES: At 4 time points
      (2 before and 2 after parturition), the total concentration of R equi and
      concentration of virulent R equi were determined in fecal specimens from mares by
      use of quantitative bacteriologic culture and a colony immunoblot technique,
      respectively. These concentrations for mares of foals that developed R equi
      associated pneumonia and for mares with unaffected foals were compared. Data for
      each year were analyzed separately. RESULTS: R equi-associated pneumonia
      developed in 53 of 171 (31%) foals. Fecal shedding of virulent R equi was
      detected in at least 1 time point for every mare; bacteriologic culture results
      were positive for 62 of 171 (36%) mares at all time points. However, compared
      with dams of unaffected foals, fecal concentrations of total or virulent R equi
      in dams of foals with R equi-associated pneumonia were not significantly
      different. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that dams of
      foals with R equi-associated pneumonia did not shed more R equi in feces than
      dams of unaffected foals; therefore, R equi infection in foals was not associated
      with comparatively greater fecal shedding by their dams. However, detection of
      virulent R equi in the feces of all mares during at least 1 time point suggests
      that mares can be an important source of R equi for the surrounding environment.

PMID- 17199421
TI  - Timing of seroconversion and acquisition of positive polymerase chain reaction
      assay results in calves experimentally infected with bovine leukemia virus.
AB  - OBJECTIVE: To determine the interval to provirus and serum antibody detection
      (via PCR assay and ELISA, respectively) in calves after experimental inoculation
      with bovine leukemia virus (BLV). ANIMALS: 8 colostrum-deprived, BLV-negative
      Holstein bull calves (> or = 6 weeks old). PROCEDURES: Via IM injection, each
      calf received a fresh whole-blood inoculum (day 0) calculated to contain 2 x
      10(6) lymphocytes. Blood samples for the ELISA and PCR assay were collected from
      calves immediately prior to inoculation and weekly thereafter for 7 weeks. Mean
      and median number of weeks to PCR-detected conversion of BLV status and
      seroconversion were calculated. Point sensitivity and cumulative sensitivity of
      the 2 assays were calculated at each sample collection. At each sampling time,
      the proportion of calves identified as infected by the cumulative weekly ELISA
      and PCR assay results was compared by use of a Fisher exact test. RESULTS: In 5
      calves, conversion of BLV status was detected via PCR assay before seroconversion
      was identified. However, seroconversion preceded PCR-detected conversion in 2
      calves. In 1 calf, both assays yielded positive results at the same test date.
      These differences were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: In
      experimentally inoculated BLV-negative calves, conversion of BLV status was
      detected via PCR assay more quickly than via ELISA; this difference was not
      significant and probably not clinically important. The PCR assay may be useful as
      a confirmatory test in animals of exceptional value; tests based on viral
      identification may become critically important if vaccines against BLV infection
      are developed and marketed.

PMID- 17199422
TI  - Expression of cyclooxygenase-1 and -2 in naturally occurring squamous cell
      carcinomas in horses.
AB  - OBJECTIVE: To assess expression of cyclooxygenase (COX)-1 and -2 in naturally
      occurring squamous cell carcinomas (SCCs) and the analogous normal tissues in
      horses. SAMPLE POPULATION: Tissue samples collected from 3 conjunctival, 2
      vulvar, 4 preputial, and 5 penile SCCs during surgical excision in 14 horses and
      from corresponding body regions (conjunctiva [n = 5 horses], vulva [2], prepuce
      [3], and penis [3]) in 5 horses euthanized for reasons unrelated to neoplasia.
      PROCEDURES: Tissue samples were snap frozen in liquid nitrogen and stored at -80
      degrees C until analysis. Protein was extracted from the frozen tissues, and
      western blot analyses were performed. Nonneoplastic and abnormal tissues from
      each body region were run on the same blot, and blots were run in triplicate.
      Molecular-weight markers and COX-1 and 2 ovine standards (positive control
      samples) were run concurrently on the gels; negative control samples were not
      used. RESULTS: All tissues, including the nonneoplastic and SCC tissues,
      expressed both COX-1 and -2 proteins. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that the expression of COX proteins in both nonneoplastic and SCC
      affected tissues in horses is markedly different from that in other species. The
      reason for the potential benefit of COX-2 inhibitors in horses and other species
      is unknown. Further research needs to be performed to evaluate the efficacy of
      COX-2 inhibitors as cancer treatments in horses. Investigation of the mechanisms
      of tumor development in horses should be performed to increase understanding of
      this disease and ascertain how the mechanisms differ from those in other animals.

PMID- 17199423
TI  - Neutrophil myeloperoxidase measurements in plasma, laminar tissue, and skin of
      horses given black walnut extract.
AB  - OBJECTIVE: To compare measurements of myeloperoxidase (MPO) in plasma, laminar
      tissues, and skin obtained from control horses and horses given black walnut
      heartwood extract (BWHE). ANIMALS: 22 healthy 5- to 15-year-old horses.
      PROCEDURES: Horses were randomly assigned to 4 groups as follows: a control group
      given water (n = 5) and 3 experimental groups given BWHE (17) via nasogastric
      intubation. Experimental groups consisted of 5, 6, and 6 horses that received
      BWHE and were euthanatized at 1.5, 3, and 12 hours after intubation,
      respectively. Control horses were euthanatized at 12 hours after intubation.
      Plasma samples were obtained hourly for all horses. Laminar tissue and skin from
      the middle region of the neck were harvested at the time of euthanasia. Plasma
      and tissue MPO concentrations were determined via an ELISA; tissue MPO activity
      was measured by use of specific immunologic extraction followed by enzymatic
      detection. RESULTS: Tissues and plasma of horses receiving BWHE contained
      significantly higher concentrations of MPO beginning at hour 3. Laminar tissue
      and skin from horses in experimental groups contained significantly higher MPO
      activity than tissues from control horses. Concentrations and activities of MPO
      in skin and laminar tissues were similar over time. CONCLUSIONS AND CLINICAL
      RELEVANCE: In horses, BWHE administration causes increases in MPO concentration
      and activity in laminar tissue and skin and the time of increased MPO
      concentration correlates with emigration of WBCs from the vasculature. These
      findings support the hypothesis that activation of peripheral WBCs is an early
      step in the pathogenesis of acute laminitis.

PMID- 17199424
TI  - Serial alterations in digital hemodynamics and endothelin-1 immunoreactivity,
      platelet-neutrophil aggregation, and concentrations of nitric oxide, insulin, and
      glucose in blood obtained from horses following carbohydrate overload.
AB  - OBJECTIVE: To quantify changes in endothelium-derived factors and relate those
      changes to various aspects of digital hemodynamics during the prodromal stages of
      carbohydrate overload (CHO)-induced laminitis in horses. ANIMALS: 20 adult horses
      without abnormalities of the digit. PROCEDURES: Digital and jugular venous blood
      samples were collected at 1-hour intervals (for assessment of endothelin-1 [ET-1]
      immunoreactivity and measurement of glucose, insulin, and nitric oxide [NO]
      concentrations) or 4-hour intervals (CBC and platelet-neutrophil aggregate
      assessment) for 8 hours or 16 hours after induction of CHO-associated laminitis
      in horses treated with an ET-1 antagonist. Effects of treatment, collection site,
      and time and the random effects of horse on each variable were analyzed by use of
      a repeated-measures model. Where treatment and collection site had no significant
      effect, data were combined. RESULTS: Compared with baseline values, CHO resulted
      in changes in several variables, including a significant increase from baseline
      in digital blood ET-like immunoreactivity at 11 hours; digital blood ET-like
      immunoreactivity was significantly greater than that in jugular venous blood at
      8, 9, 11, and 12 hours. Digital and jugular venous blood concentrations of
      glucose increased from baseline significantly at 3, 4, and 5 hours; insulin
      concentration increased significantly at 5 hours; and the number of platelet
      neutrophil aggregates increased significantly at 12 hours. CONCLUSIONS AND
      CLINICAL RELEVANCE: In horses, concurrent increases in venous blood ET-1
      immunoreactivity, insulin and glucose concentrations, and platelet-neutrophil
      aggregates support a role of endothelial dysfunction in the pathogenesis of CHO
      induced laminitis.

PMID- 17199425
TI  - Induction of chemoresistance in a cultured canine cell line by retroviral
      transduction of the canine multidrug resistance 1 gene.
AB  - OBJECTIVE: To induce chemoresistance in a normal canine cell line through the
      transduction of the canine multidrug resistance 1 gene (mdr1). SAMPLE POPULATION:
      Madin-Darby canine kidney (MDCK) epithelial cell line. PROCEDURES: The full
      length canine mdr1 cDNA clone isolated in our laboratory was inserted into a
      Moloney murine leukemia virus-based vector to construct the retroviral vector,
      pLNC-cMDR1. After retroviral transduction of pLNC-cMDR1 into MDCK cells, the
      expression and function of the P-glycoprotein, a product of mdr1, were assessed
      by immunoblotting, measurement of rhodamine123 (Rh123) retention, and drug
      sensitivity assays. RESULTS: P-glycoprotein was strongly expressed in cells
      transduced with pLNC-cMDR1. This P-glycoprotein was fully functional, as
      demonstrated by the decreased Rh123 retention and the increased resistance to
      chemotherapeutic drugs. Measured as 50% inhibitory concentrations, resistance
      increased 59 times to vincristine and 25 times to doxorubicin in MDCK cells after
      transduction of pLNC-cMDR1. CONCLUSIONS AND CLINICAL RELEVANCE: Transduction of
      canine mdr1 is an effective method for inducing chemoresistance in normal canine
      cells. This system may be applicable to the induction of drug resistance in
      hematopoietic cells.

PMID- 17199426
TI  - Bioavailability of a commercial formulation of ivermectin after subcutaneous
      administration to sheep.
AB  - OBJECTIVE: To evaluate bioavailability and other pharmacokinetic variables of a
      commercial formulation of ivermectin after IV administration to sheep. ANIMALS: 6
      healthy adult sheep. PROCEDURES: A single dose of a commercial formulation of
      ivermectin (200 microg/kg) was administered IV to each sheep. After a washout
      period of 3 weeks, each sheep was administered ivermectin by SC injection. Plasma
      samples were obtained for up to 36 and up to 42 days after IV and SC
      administration, respectively. Ivermectin concentrations were quantified by use of
      high-performance liquid chromatography with fluorescence detection. RESULTS:
      Results obtained indicated that after IV administration, ivermectin is cleared
      slowly from plasma, tends to distribute and accumulate in the peripheral
      compartment, and is slowly eliminated from the body. After SC administration,
      noncompartmental analysis revealed that bioavailability of ivermectin is nearly
      complete (98.20%), has a slow mean absorption time of 0.96 days, and reaches a
      maximum plasma concentration of 19.55 ng/mL at 3.13 days. CONCLUSIONS AND
      CLINICAL RELEVANCE: The commercial formulation of ivermectin used in this study
      can be administered SC to sheep on the basis of a nearly complete
      bioavailability. In addition, the maximum plasma concentration and interval from
      SC injection until maximum plasma concentration is obtained are higher than those
      reported by other authors who used other routes of administration.

PMID- 17199427
TI  - Effect of strenuous exercise on urine concentrations of homovanillic acid,
      cortisol, and vanillylmandelic acid in sled dogs.
AB  - OBJECTIVE: To determine whether prolonged exercise by conditioned sled dogs
      affects urine concentrations of homovanillic acid (a metabolite of dopamine),
      vanillylmandelic acid (a metabolite of norepinephrine and epinephrine), and
      cortisol. ANIMALS: 24 conditioned Alaskan sled dogs (2 to 8.5 years old) that
      were in training for a multiday endurance race. PROCEDURES: Voided urine samples
      were collected from 4 groups of dogs (randomly selected from 54 dogs) after no
      exercise (control group; n = 6 dogs), completion of a 160km run (group A; 3),
      completion of a 420-km run (group B; 7), and completion of a 560-km run (group C;
      6). Urine cortisol concentrations were determined by use of an immunoassay
      technique; urine vanillylmandelic acid and homovanillic acid concentrations were
      measured via high-performance liquid chromatography. RESULTS: Compared with the
      control group, urine cortisol concentration in groups A, B, and C was
      significantly different (5.33 x 10(4) +/- 2.62 x 10(4) microg/dL vs 1.04 x 10(4)
      +/- 2.31 x 10(5) microg/dL, 8.88 x 10(4) +/- 5.49 x 10(4) microg/dL, and 6.31 x
      10(4) +/- 5.09 x 10(4) microg/dL, respectively). Urine homovanillic acid
      concentration did not differ among the 4 groups. Vanillylmandelic acid was not
      detected in any urine samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      indicated that prolonged exercise by sled dogs did not affect urine homovanillic
      acid concentration but did increase urinary cortisol secretion, which is
      indicative of adrenocortical stimulation. The apparent lack of vanillylmandelic
      acid in voided urine samples requires further investigation.

PMID- 17199429
TI  - Effects of TSH receptor mutations on binding and biological activity of
      monoclonal antibodies and TSH.
AB  - The effects of an extensive series of mutations in the TSH receptor (TSHR)
      leucine-rich domain (LRD) on the ability of thyroid-stimulating monoclonal
      antibodies (TSMAbs) and TSH to bind to the receptor and stimulate cyclic AMP
      production in TSHR-transfected CHO cells has been investigated. In addition, the
      ability of a mouse monoclonal antibody with blocking (i.e., antagonist) activity
      (RSR-B2) to interact with mutated receptors has been studied. Several amino acids
      distributed along an extensive part of the concave surface of the LRD were found
      to be important for binding and stimulation by the thyroid-stimulating human MAb
      M22 but did not appear to be important for TSH binding and stimulation. Most of
      these amino acids important for M22 interactions were also found to be important
      for the stimulating activity of six different mouse TSMAbs and a hamster TSMAb.
      Furthermore, most of these same amino acids were important for stimulation by
      TSHR autoantibodies in a panel of sera from patients with Graves' disease. Amino
      acid R255 was the only residue found to be unimportant for TSH stimulation but
      critical for stimulation by all thyroid-stimulating antibodies tested (23 patient
      serum TSHR autoantibodies, M22, and all seven animal TSMAbs). About half the
      amino acids (all located in the N-terminal part of the LRD) found to be important
      for M22 activity were also important for the blocking activity of RSR-B2 and
      although the epitopes for the two MAbs overlap they are different. As the two
      MAbs have similar affinities, their epitope differences are probably responsible
      for their different activities. Overall our results indicate that different
      TSMAbs and different patient sera thyroid-stimulating autoantibodies interact
      with the same region of the TSHR, but there are subtle differences in the actual
      amino acids that make contact with the different stimulators.

PMID- 17199430
TI  - Thyroid hormone regulates endogenous amyloid-beta precursor protein gene
      expression and processing in both in vitro and in vivo models.
AB  - Thyroid hormone negatively regulates the amyloid-beta precursor protein (APP)
      gene in thyroid hormone receptor (TR)-transfected neuroblastoma cells. A negative
      thyroid hormone response element (nTRE) that mediates this regulation has been
      identified in the first exon of the APP gene. We demonstrate in an in vivo system
      that expression of APP mRNA, APP protein, and APP secretase cleavage products in
      mouse brain is influenced by thyroid status. Adult female mice were made
      hyperthyroid or hypothyroid for 3 weeks and compared to euthyroid mice. APP gene
      product expression was increased in hypothyroid mouse brain and reduced in
      hyperthyroid mouse brain, when compared to euthyroid controls. We observed
      similar effects of thyroid hormone on endogenous APP gene expression in human
      neuroblastoma cells. The incidence of hypothyroidism increases with age, and
      localized hypothyroidism of central nervous system has been reported in some
      patients with Alzheimer's disease (AD). Reduced action of thyroid hormone on the
      APP gene may contribute to AD pathology by increasing APP expression and the
      levels of processed APP products. These findings may be an underlying mechanism
      contributing to the association of hypothyroidism with AD in the elderly, as well
      as identifying a potential therapeutic target. Pharmacologic supplementation of
      thyroid hormone, or its analogs, may reduce APP gene expression and beta amyloid
      peptide accumulation.

PMID- 17199431
TI  - Estrogen receptor (ER)-beta, but not ER-alpha, is present in thyroid vessels:
      immunohistochemical evaluations in multinodular goiter and papillary thyroid
      carcinoma.
AB  - OBJECTIVE: Estrogen receptors (ERs) have been demostrated in the vessel
      structures of several systems. Little is known on the presence of ERs in the
      thyroid vessels. DESIGN: We immunohistochemically evaluated both ER-alpha and ER
      beta immunoreactivity (IR) in both vascular and follicular thyroid cells in
      tissue samples from 17 cases of multinodular goiter (MNG) and 17 cases of
      papillary thyroid carcinoma (PTC). MAIN OUTCOME: ER-alpha IR was undetectable in
      either tissue examined. In 100% of MNG samples, nuclear ER-beta IR was detected
      in both endothelial and follicular cells. In PTC samples, endothelial nuclear ER
      beta IR was found in 100% of cases, whereas the nuclear staining of follicular
      cells was found in 83% of cases. The intensity of staining of the endothelial ER
      beta IR was comparable between MNG and PTC. However, when follicular cells were
      considered, a tendency toward a decrease in nuclear staining and a significant
      increase in cytoplasmic staining were found in PTC lesions as compared to MNG.
      CONCLUSIONS: This study demonstrated that ER-beta, but not ER-alpha, IR is
      present in the endothelium of thyroid vessels. Furthermore, although data need to
      be confirmed in larger observations, these results suggest the lack of
      differences in the pattern of vascular ER-beta IR between MNG and PTC.

PMID- 17199432
TI  - HLA-DR3 transgenic mice immunized with adenovirus encoding the thyrotropin
      receptor: T cell epitopes and functional analysis of the CD40 Graves'
      polymorphism.
AB  - The major histocompatibility (MHC) molecule HLA-DR3 is a susceptibility gene for
      Graves' disease (GD) in Caucasians. Mice lacking murine MHC and expressing human
      HLA-DR3 develop thyrotropin receptor (TSHR) antibodies and sometimes
      hyperthyroidism after vaccination with TSHR-DNA. MHC molecules present peptides
      processed from antigens to T cells. Therefore, we used DR3-transgenic mice to
      investigate recognition of TSHR ectodomain peptides. After immunization with TSHR
      A-subunit adenovirus (A-subunit-Ad) but not control-adenovirus (Control-Ad),
      splenocytes from DR3 mice responded to A-subunit protein in culture by producing
      interferon-gamma (IFN-gamma). When challenged with 29 overlapping TSHR peptides,
      splenocytes from A-subunit-Ad- or Control-Ad-immunized mice responded to several
      peptides. However, in splenocytes from A-subunit-Ad but not Control-Ad mice, a
      peptide containing TSHR residues 142-161 induced significantly more IFN-gamma
      than the same splenocytes in medium alone. Immunized DR3 mice also permitted
      testing the TSHR-specific function of the CD40 single nucleotide polymorphism (C
      vs. T) associated with GD. Of three human DR3 human Epstein-Barr virus lines
      (EBVL), two had C in both alleles (CC) and one was CT. However, these EBVL
      presented peptides poorly and there was no difference between CC vs. CT EBVL in
      peptide presentation to splenocytes from immunized mice. A peptide corresponding
      to residues 145-163 is one of seven suggested to be important in GD based on HLA
      binding affinities, T-epitope algorithms, and human studies. Consequently, as in
      human GD, TSHR amino acids 142-161 appear to include a major T cell epitope in
      HLA-DR3 transgenic mice immunized with A-subunit-Ad.

PMID- 17199433
TI  - Outcomes of patients with differentiated thyroid carcinoma following initial
      therapy.
AB  - This analysis was performed to determine the effect of initial therapy on the
      outcomes of thyroid cancer patients. The study setting was a prospectively
      followed multi-institutional registry. Patients were stratified as low risk
      (stages I and II) or high risk (stages III and IV). Treatments employed included
      near-total thyroidectomy, administration of radioactive iodine, and thyroid
      hormone suppression therapy. Outcome measures were overall survival, disease
      specific survival, and disease-free survival. Near-total thyroidectomy,
      radioactive iodine, and aggressive thyroid hormone suppression therapy were each
      independently associated with longer overall survival in high-risk patients. Near
      total thyroidectomy followed by radioactive iodine therapy, and moderate thyroid
      hormone suppression therapy, both predicted improved overall survival in stage II
      patients. No treatment modality, including lack of radioactive iodine, was
      associated with altered survival in stage I patients. Based on our overall
      survival data, we confirm that near-total thyroidectomy is indicated in high-risk
      patients. We also conclude that radioactive iodine therapy is beneficial for
      stage II, III, and IV patients. Importantly, we show for the first time that
      superior outcomes are associated with aggressive thyroid hormone suppression
      therapy in high-risk patients, but are achieved with modest suppression in stage
      II patients. We were unable to show any impact, positive or negative, of specific
      therapies in stage I patients.

PMID- 17199434
TI  - Characterization of follicular thyroid nodules at fine needle aspiration biopsy
      using double phase thallium-201 imaging: comparison of visual and
      semiquantitative analyses.
AB  - OBJECTIVE: To compare visual and semiquantitative indices of double phase
      thallium-201 thyroid scintigraphy (DTS) for differentiation of malignant nodules
      by indeterminate fine needle aspiration biopsy (FNAB) results. DESIGN: DTS
      (early; 15 minutes; delayed, 2 hour) were performed after injection of 37MBq of
      thallium-201 in 60 patients with indeterminate FNAB. MAIN OUTCOME: With grade 4
      and 5, sensitivity and specificity were 51.4% and 78.3%, respectively. With early
      lesion to nonlesion ratio (L/N) 1.49, sensitivity and specificity were 97.3% and
      39.1%, respectively. With delayed L/N 1.89, sensitivity and specificity were
      70.3% and 78.3%, respectively. With wash-out rate (WR) 18.93%, sensitivity and
      specificity were 89.2% and 82.6%. Early L/N was superior to delayed L/N and WR
      for the detection of malignant thyroid nodules. CONCLUSION: Visual assessment had
      a limited value for differentiation of follicular nodules. The optimal
      semiquantitative indices were 1.49 for early L/N and 1.89 for delayed L/N. Also,
      optimal WR was 18.93%. The early L/N was superior to delayed L/N and WR for the
      detection of malignant thyroid nodular lesions. However, visual assessment and
      early L/N of DTS showed similar results. Visual analysis and semiquantitative
      indices of DTS could not differentiate follicular carcinoma and follicular
      variant of papillary thyroid cancer.

PMID- 17199435
TI  - Continued suppression of serum TSH level may be attributed to TSH receptor
      antibody activity as well as the severity of thyrotoxicosis and the time to
      recovery of thyroid hormone in treated euthyroid Graves' patients.
AB  - The cause of continued suppression of serum thyroid-stimulating hormone (TSH)
      levels during antithyroid drug therapy in some Graves' patients is unclear.
      Recently, there has been a notable explanation involving the direct inhibition of
      TSH receptor antibody (TRAb) on TSH secretion in the pituitary gland. The purpose
      of this study is to verify the relation between TRAb or other clinical parameters
      and the continued suppression of serum TSH level during antithyroid drug therapy
      in patients with Graves' disease. We reviewed the medical records of patients
      with Graves' disease between 1995 and 2002 at Samsung Medical Center. We selected
      167 Graves' patients who had been euthyroid for at least 12 months after recovery
      of serum T3 and T4 levels during the antithyroid drug therapy. We analyzed the
      correlation of the interval until recovery of serum TSH with the pretreatment
      clinical parameters. We compared the recovery rates of suppressed TSH levels
      between pretreatment thyrotrophin-binding inhibitory immunoglobulin (TBII)
      positive (>15%) and TBII-negative patients. We also compared the clinical
      parameters between two groups at the time of diagnosis and after recovery of
      thyroid hormone. Pretreatment serum T3 level, (131)I uptake, TBII activity, and
      the time to recovery of T3 or T4/free T4 level showed significant positive
      correlations with the interval until recovery of serum TSH level ( p < 0.05).
      Recovery rates of serum TSH levels at 3 months after recovery of thyroid hormone
      were significantly lower in pretreatment TBII-positive patients than those in
      TBII-negative patients ( p < 0.01). Serum TSH levels were significantly lower in
      TBII-positive patients at 3 months after recovery of thyroid hormone ( p < 0.05).
      TBII activities inversely correlated only with serum TSH levels at 3months after
      recovery of thyroid hormone ( p < 0.001). In conclusion, continued suppression of
      serum TSH level may be attributed to TRAb activity as well as the pretreatment
      severity of thyrotoxicosis and the time to recovery of thyroid hormone in
      patients with Graves' disease during antithyroid drug therapy.

PMID- 17199436
TI  - Serum Ghrelin Levels in patients with Hashimoto's thyroiditis.
AB  - OBJECTIVE: Hypothyroidism is associated with changes in appetite and body weight.
      Ghrelin is an orexigenic peptide, and it stimulates appetite and increases food
      intake. However, the potential relationship between circulating ghrelin levels,
      hypothyroidism, and thyroid antibodies has not been adequately studied. DESIGN:
      Forty-seven patients with hypothyroidism due to Hashimoto's thyroiditis and 48
      euthyroid subjects were enrolled in the study. Thyroid hormones and antibodies,
      insulin, glucose, ghrelin levels, and lipid parameters were measured in all the
      subjects. MAIN OUTCOME: Hypothyroid group showed significantly decreased serum
      levels of ghrelin and ghrelin=body mass index (BMI) compared to euthyroid group
      (31.9 +/- 21.5 pg/mL vs. 50.5 +/- 34.8 pg/mL, p < 0.001; and 1.24 +/- 0.93 vs.
      2.12 +/- 1.53, p < 0.0001). In hypothyroid group, 6 months after treatment,
      ghrelin levels and ghrelin/BMI remained lower than euthyroid group (33.2 +/- 21.1
      pg/mL vs. 50.5 +/- 34.8 pg/mL, p < 0.001; and 1.27 +/- 0.86 vs. 2.12 +/- 1.53, p
      < 0.0001). Ghrelin levels were decreased in hypothyroid patients with high
      thyroid peroxidase antibody (TPOAb) titre compared to hypothyroid patients with
      low TPOAb titre (19.1 +/- 23.1 pg/ mL vs. 35.3 +/- 17.4 pg/mL, p < 0.01). Ghrelin
      levels correlated positively with free triiodothyronine (FT3) and free thyroxine
      (FT4), and negatively with age, thyroglobulin antibody (TAb), TPOAb, total
      cholesterol (T-C), low-density lipoprotein cholesterol (LDL-C), very low-density
      lipoprotein cholesterol (VLDL-C), and triglycerides (TG) in hypothyroid group. In
      euthyroid group, circulating ghrelin levels correlated negatively with age, FT3,
      FT4, TG, and VLDL-C levels. No significant correlation was observed between
      ghrelin and homeostasis model assessment for insulin resistance (HOMA-IR) and
      between ghrelin and quantitative insulin sensitivity check index (QUICKI) in both
      groups. Regression analysis revealed that FT3 level is the most important
      predictor of ghrelin levels. CONCLUSION: Thyroid hormones and antibodies seem to
      have a potential effect on serum ghrelin levels in patients with hypothyroidism.

PMID- 17199437
TI  - High prevalence of thyroid dysfunction and autoimmune thyroiditis in adolescents
      after elimination of iodine deficiency in the Eastern Black Sea Region of Turkey.
AB  - In the present study we evaluated the effects of iodine intake on the prevalence
      of thyroid dysfunction, autoimmunity, and goiter in two regions with different
      iodine status after two years of iodization in Turkey. In total 1733 adolescent
      subjects were enrolled into the study (993 from an iodine-sufficient area--the
      Eastern Black Sea Region (group 1) and 740 from an iodine-deficient area--Middle
      Anatolia (group 2)). We measured free thyroxine (FT(4)), thyrotropin (TSH),
      antithyroid peroxidase antibodies (Anti-TPO), antithyroglobulin antibodies (Anti
      Tg), and urinary iodine (UI), and examined the thyroid gland by ultrasound.
      Median urinary iodine excretion was found to be significantly different in group
      1 and group 2 (139 micro/l vs 61micro/l, p < 0.001). Hyperthyroidism was more
      frequent in group 1 (3.6% vs 0.7%; p < 0.001), but the hypothyroidism rate was
      similar between groups (1.8% vs 1.4 %; p>0.05). The percentage of anti-Tg
      positive subjects was found to be 17.6% in group 1 and 6.4% in group 2; that of
      anti-TPO positive subjects was 4.3% in group 1 and 1.5% in group 2. The
      prevalence of antithyroid antibody (anti-Tg and/or anti-TPO) positivity was
      significantly higher in group 1 than in group 2 (18.52% vs 6.62%; p < 0.001).
      Thyroid volumes of the hyperthyroid subjects in both groups were significantly
      higher than hypo- and euthyroid subjects. In conclusion, iodine supplementation
      in Turkey has resulted in the elimination of iodine deficiency in the Eastern
      Black Sea Region, and this has been accompanied by an increase in the prevalence
      of autoimmune thyroiditis and thyroid dysfunction.

PMID- 17199438
TI  - Sequential follow-up of serum thyroglobulin and whole body scan in thyroid cancer
      patients without initial metastasis.
AB  - OBJECTIVE: To investigate the usefulness of whole body scan (WBS) and serum
      thyroglobulin (Tg) measurement after thyroxine withdrawal during sequential
      follow-ups in patients with differentiated thyroid cancer (DTC). DESIGN: Two
      hundred and sixty-five consecutive DTC patients were enrolled. They were
      previously treated with near-total thyroidectomy and I-131 remnant ablation,
      without initial metastases or Tg antibodies. All had the first follow-up WBS and
      serum Tg measurement 6-12 months after initial treatment, and 165 patients
      received the second follow-up without further therapy. Positive/negative
      predictive values (PPV/NPV) were calculated by the outcome of patients being
      followed up for more than 8 years (mean+/-SD: 133+/-26 months). RESULTS: Serum Tg
      levels while the patients were off thyroxine therapy decreased spontaneously in
      39.3% of the cases without further therapy. The NPV of the first follow-up serum
      Tg level was excellent: <2 microg/L and <0.5 microg/L were 95.1% and 98.2%,
      respectively. However, the PPV of the first follow-up serum Tg level was low: >10
      microg/L and 2-10 microg/L were 40% and 9.6%, respectively. The trend of Tg
      levels was more informative; the PPV was 62.5% in cases with an increase of serum
      Tg of >10 microg/L and 16.6% with an increase of <5 microg/L. However, decreasing
      Tg levels may associate with rapid deterioration of disease, in which cases
      decrease of Tg indicated dedifferentiation of the tumor. The diagnostic WBS
      showed the same picture in 91.5% of the patients. Only one patient (0.6%) turned
      from negative study to positive during the follow-up. In the meanwhile his serum
      Tg levels increased from 0.56 to 13.6 microg/L. CONCLUSION: It is most
      informative when both the trend and the levels of Tg during sequential follow-up
      are considered. The diagnostic WBS may be performed for selected patients with
      indication based on Tg levels to localize the disease.

PMID- 17199439
TI  - L-T4 bioequivalence and hormone replacement studies via feedback control
      simulations.
AB  - FDA Guidance for testing bioequivalence of levothyroxine (L-T(4)) preparations
      has been challenged by several groups, based on multiple issues. The efficacy of
      single versus combined hormone therapy also is receiving additional scrutiny. To
      examine these concerns, we developed a new nonlinear feedback system simulation
      model of whole-body regulation mechanisms involving dynamics of T(3), T(4), TSH,
      plasma protein binding, extravascular regulatory enzyme systems, and the
      hypothalamic-pituitary-thyroid axis, all quantified from human data. To address
      bioequivalence, we explored how to best account for varying and unmeasured
      endogenous T(4) following dosing with exogenous oral L-T(4) in euthyroid
      volunteers in required pharmacokinetic (PK) studies, by simulating various dosing
      scenarios and developing a new and simple correction method. We computed and
      assessed dosing error effects and baseline corrections using simulator-predicted
      endogenous T(4) level variations, due to actual closed-loop effects, and compared
      these with approximate corrections computed directly from PK data. Predicted dose
      responses were quite linear, and for constant baseline, 7-day half-life, and our
      new formula-correction methods, we established some bounds on bioequivalent
      dosages. Simulated replacement after thyroidectomy required 141 microg L-T(4)
      only to normalize T(3) tissue levels and 162 microg L-T(4) to normalize plasma
      T(3) levels. A combined dose of approximately 103 microg L-T(4) plus
      approximately 6 microg T(3) ( approximately 18:1 ratio) was needed to normalize
      both plasma T(3) and T(4) and average tissue T(3) levels. However, simulated
      average tissue T(3) levels were normalized with standard L-T(4)-only therapy, and
      plasma T(3) levels were still within the normal range. We suggest a simple and
      more accurate correction for endogenous T(4) in PK studies. Current standard L
      T(4)-only treatment is supported for routine replacement needs.

PMID- 17199440
TI  - Molecular diagnosis of a BRAF papillary thyroid carcinoma with multiple
      chromosome abnormalities and rare adrenal and hypothalamic metastases.
AB  - OBJECTIVE: Molecular characterization of thyroid tumors is rarely applied to
      patient management. Our aim was to demonstrate the application of molecular and
      cell biology to patient care. DESIGN: Clinical and molecular case study. MAIN
      OUTCOMES: A 57-year-old man with papillary thyroid carcinoma presented with
      adrenal and several other presumed metastases, pulmonary nodules, and mediastinal
      lymphadenopathy. Bronchial carcinoma was entertained for the pulmonary lesions
      because of a tobacco history. Mediastinal lymph node biopsy was nondiagnostic.
      Cells from the biopsy were grown in tissue culture and characterized by
      immunocytochemical (ICC), allele-specific polymerase chain reaction (PCR),
      reverse transcription (RT)-PCR, DNA sequencing, and cytogenetics. A panel of
      agents were tested the cells for tumoricidal activity. The cells expressed
      thyroid-specific markers [thyroid-stimulating hormone receptor (TSH-R),
      thyroglobulin (TG), sodium iodide symporter (NIS)] and markers [thyroid
      transcription factor-1 (TTF-1), cytokeratin-7, epidermal growth factor receptor
      (EGF-R)] present in the primary tumor and adrenal metastasis. The BRAF V600E
      mutation was detected. The karyotype was 44-48,XY, + der(1)
      t(1;9)(p13;p13),add(9)(p13),-17,-18, + 0-3mar[cp20]. Lovastatin, gefitinib,
      paclitaxel, depsipeptide, and 17-AAG inhibited the growth of the cultured cells.
      Combinations of two or three drugs produced additive or synergistic effects
      depending upon the combination. CONCLUSIONS: Unusual metastases may be associated
      with multiple molecular and cytogenetic abnormalities. Thus, molecular and cell
      biological studies can allow otherwise difficult thyroid tumor diagnosis and may
      be used for targeted, individualized selection of potential treatments.

PMID- 17199442
TI  - Malignant teratoma of the thyroid: case report.
AB  - Teratomas in the neck are rare neoplasms. Most of them occur in infants less than
      1 year and are benign. In contrast, thyroid teratomas in adults are malignant and
      have fatal outcomes because of spread of tumor refractory to treatment. We report
      a case of a primary thyroid malignant teratoma in a 37-year-old woman. She was
      treated successfully with a combination of surgery, postoperative cis-platinum
      based chemotherapy, and radiation therapy to the neck. Although the time of
      follow-up is short (24 months), we attribute her successful outcome to the use of
      this intensive therapeutic approach.

PMID- 17199441
TI  - A novel mutation in the thyrotropin (thyroid-stimulating hormone) receptor gene
      in a case of congenital hypothyroidism.
AB  - Congenital hypothyroidism (CH) occurs approximately with a frequency of 1 in 3000
      4000 births, being a disease caused by defects in thyroid hormone synthesis
      associated either with goiter presence or with agenesis or ectopy of the thyroid
      gland. A study of some familial cases has allowed identification of mutations in
      several known genes, including that encode the thyroid-stimulating hormone
      receptor (TSHR). We report a familial case of CH that transmitted as a recessive
      trait and caused by a novel homozygous nonsense mutation in TSHR with an initial
      diagnosis of thyroid agenesis hypoplasia. Genomic DNA was obtained from two
      siblings and their parents; TSHR was amplified using pairs of overlapping exonic
      primers; and polymerase chain reaction products were automatically sequenced. The
      propositus was homozygous (genotype: M/M) for a novel C to G transversion
      (1431C>G), producing a nonsense mutation, Y444X, in the first intracellular loop
      of TSHR, rendering a truncated receptor. Thus, the observed unresponsiveness to
      TSHR may be due to absent insertion of the truncated receptor into the cell
      membrane (if it gets translated at all) or the truncation may lead to nonsense
      mediated mRNA degradation (its unresponsive to TSH). Both parents were
      heterozygous (wWt/M) and unrelated, as known from family history. The other
      daughter was homozygous for both wild-type alleles (wWt/wWt).

PMID- 17199443
TI  - Renal cyst uptake following I-131 treatment for thyroid cancer.

PMID- 17199444
TI  - An asymptomatic thoracic aortic aneurysm mimicking an intrathoracic goiter.

PMID- 17199445
TI  - Cystic papillary thyroid cancer.

PMID- 17199447
TI  - The measurement of rapid parathyroid hormone for predicting symptomatic
      hypocalcemia in postanesthesia care unit after total thyroidectomy is safe and
      effective.

PMID- 17199446
TI  - Paradoxical reaction on treatment with 131I.

PMID- 17199448
TI  - Iodine intake in Argentina.

PMID- 17199450
TI  - Mind over matter: exploring job stress among female blue-collar workers.
AB  - Although overall health has been defined holistically as the integration of a
      person's optimal mental, physical, social, intellectual, and spiritual well
      being, a mental health focus remains on the fringe of many public health efforts.
      This report describes recent efforts by the Centers for Disease Control and
      Prevention (CDC) to explore job stress among female blue-collar workers. Using a
      more holistic approach to understand its impact on blue-collar women's overall
      health, health-related quality of life (HRQOL) was used to assess optimal human
      performance. Attempting to encapsulate how overall health affects one's ability
      to participate and fulfill daily personal/professional tasks, HRQOL yields a
      broader understanding of the interaction between psychological well-being (mind)
      and physical functioning (matter). Embedding CDC HRQOL-4 measures into a
      questionnaire used as part of a larger mixed methods project, blue-collar women
      responded to questions about their health, including both mental and physical.
      For these female workers, mental health appeared to be of greater consequence,
      which could be interpreted as mind being more significant than matter. This paper
      highlights the findings related to HRQOL issues experienced by these female blue
      collar workers and summarizes recommendations for effective individual and
      organizational approaches to address job stress.

PMID- 17199451
TI  - Toward optimal health: Eva Selhub, M.D., discusses mind-body medicine for women.
      Interview by Jodi R. Godfrey.

PMID- 17199452
TI  - Serious gaps: how the lack of sex/gender-based research impairs health.

PMID- 17199453
TI  - Adherence to federal guidelines for reporting of sex and race/ethnicity in
      clinical trials.
AB  - BACKGROUND: The National Institutes of Health Revitalization Act of 1993 requires
      that NIH-funded clinical trials include women and minorities as subjects; other
      federal agencies have adopted similar guidelines. The objective of this study was
      to determine the current level of compliance with these guidelines in federally
      funded randomized controlled trials. METHODS: Randomized controlled trials
      published in nine influential medical journals in 2004 were identified by PubMed
      search. Studies where individuals were not the unit of analysis, those begun
      before 1994, and those not receiving federal funding were excluded. Included
      studies were examined to determine sample characteristics and presence of
      subgroup reporting. RESULTS: PubMed located 589 published papers. After exclusion
      of ineligible papers, 69 remained for analysis. Among 46 clinical studies
      enrolling both men and women, women were generally underrepresented, comprising
      on average 37% of the sample and only 24% of the sample when analysis was
      restricted to drug trials. Eighty-seven percent of the studies did not report any
      outcomes by sex or include sex as a covariate in modeling. Among all 69 studies,
      18% did not break down sample sizes by racial and ethnic groups, and 87% did not
      provide any analysis by racial or ethnic groups. Only 5 studies indicated that
      the generalizability of their results may be limited by lack of diversity among
      those studied. CONCLUSIONS: These findings illustrate inadequate compliance with
      the NIH guidelines. Researchers, editors, and journal audiences share the
      responsibility of ensuring compliance with our country's policies regarding
      federally funded research to effect healthcare improvements for all.

PMID- 17199454
TI  - Treatment considerations in women with schizophrenia.
AB  - Schizophrenia is a challenging and complex psychiatric disorder. It is a chronic
      disorder of thought, affect, and cognition that significantly disturbs the
      individual's ability to function in society and develop interpersonal
      relationships. The clinical presentation can be extremely varied, with symptoms
      including delusional thinking, disorganized thoughts and speech, hallucinatory
      behavior, and negative symptoms (e.g., blunted affect, avolition, alogia,
      anhedonia). Approximately 1% of the population is affected by schizophrenia
      worldwide, and women may experience different symptoms, have a later age of
      onset, may respond to different treatments, and may be more concerned about
      specific side effects than men. Women with schizophrenia traditionally have been
      treated in the same way as men and have generally had poorer comprehensive
      medical care. With the introduction of many new antipsychotic medications in
      recent years, this review focuses on sex differences in schizophrenia, with an
      emphasis on differences in treatment and side effects. Additionally, it presents
      patient counseling issues in sexuality and health outcomes.

PMID- 17199455
TI  - Impact of smoking cessation on bone mineral density in postmenopausal women.
AB  - BACKGROUND: Although clinical guidelines recommend smoking cessation to improve
      bone health, the impact of short-term smoking cessation (i.e., 1 year) on bone
      mineral density (BMD) is not known. We examined the effects of smoking cessation
      on BMD measurements, markers of bone turnover, and hormone profiles in
      postmenopausal women. METHODS: Postmenopausal women (n = 152) who smoked at least
      10 cigarettes per day were randomly assigned to behavioral counseling and either
      nicotine or placebo patch for smoking cessation (3-month treatment with a 1-month
      taper) and followed for an additional year. The BMD at various sites (hip, spine,
      wrist, and total body), serum and urine biochemical markers of bone turnover, and
      sex hormones were measured at baseline and again 1 year after smoking treatment.
      Women who continuously abstained from smoking between the end of treatment and 1
      year later (quitters) (n = 42) were compared with women who completed the study
      and continued to smoke (n = 77). RESULTS: Femoral trochanter BMD increased by
      2.9% among quitters vs. 0.6% among continued smokers (p = 0.02). Total hip BMD
      increased by 1.52% among quitters vs. 0.43% among continued smokers (p = 0.03).
      Changes in BMD at the femoral neck, radius, spine, and total body did not
      significantly differ between groups. The effects of smoking cessation on bone
      were mediated in part by weight gain. Smoking cessation was also associated with
      an increase in bone alkaline phosphatase. CONCLUSIONS: Smoking cessation,
      relative to continued smoking, increases BMD at the femoral trochanter and total
      hip in postmenopausal women.

PMID- 17199456
TI  - Elderly women diagnosed with nonspecific chest pain may be at increased
      cardiovascular risk.
AB  - BACKGROUND: Women are more likely than men to have nonspecific chest pain (NSCP)
      symptoms. The long-term outcomes in women discharged with a diagnosis of NSCP are
      unknown. METHODS: The Women's Health Initiative Observational Study enrolled
      postmenopausal women aged 50-79 years. After excluding those with prior
      cardiovascular disease (CVD), 83,622 women were studied. NSCP cases were defined
      as having an initial primary hospital discharge diagnosis of NSCP (ICD-9 codes
      786.50, 786.51, 786.59) without a prior diagnosis of coronary heart disease
      (CHD). Risks of subsequent CHD events were estimated from Cox proportional hazard
      ratio (HR) models stratified by clinic and adjusted for baseline age,
      cardiovascular risk factors, and hormone use. RESULTS: Over an average of 8 years
      of follow-up, 11% (230 of 2,092) of women with NSCP experienced a cardiovascular
      event compared with 9.5% (7,724 of 81,530) who did not. Compared with women
      without a hospitalization for NSCP during follow-up, those with NSCP had a
      greater than 2-fold higher risk of a subsequent hospitalization for clinically
      diagnosed angina (HR 2.18, 95% CI 1.66-2.86) and at least a 1.5-fold higher risk
      of nonfatal myocardial infarction (MI) (HR 1.59, 1.10-2.31), revascularization
      (HR 1.67, 1.28-2.20), and congestive heart failure (HR 1.75, 1.27-2.41). Women
      with NSCP who subsequently experienced a CHD event were more likely to be over
      age 65 or to have cardiovascular risk factors. CONCLUSIONS: Older women
      discharged with a diagnosis of NSCP may be at increased risk of CHD morbidity.
      Further research is needed to replicate these findings in other populations.

PMID- 17199457
TI  - Race/ethnicity, socioeconomic status, and lifetime morbidity burden in the
      women's health initiative: a cross-sectional analysis.
AB  - OBJECTIVES: We sought to assess the extent to which race/ethnicity and
      socioeconomic status (SES) are independently and jointly related to lifetime
      morbidity burden by comparing the impact of SES on lifetime morbidity among women
      of different racial/ethnic groups: white, black, Hispanic, American Indian/Alaska
      Native (AIAN), and Asian/Pacific Islander (API). METHODS: Using baseline data
      from the Women's Health Initiative (WHI), a national study of 162,000
      postmenopausal women, we measured lifetime morbidity burden using a modified
      version of the Charlson Index, and measured SES with educational attainment and
      household income. In multivariable simple polytomous logistic regression models,
      we first assessed the effect of SES on lifetime morbidity burden among women of
      each racial/ethnic group, then assessed the combined effect of race/ethnicity and
      SES. RESULTS: Five percent of all women in the study population had high lifetime
      morbidity burden. Women with high lifetime morbidity were more likely to be AIAN
      or black; poor; less educated; divorced, separated, or widowed; past or current
      smokers; obese; uninsured or publicly insured. Lower SES was associated with
      higher morbidity among most women. The extent to which morbidity was higher among
      lower SES compared to higher SES women was about the same among Hispanic women
      and white women, but was substantially greater among black and AIAN women
      compared with white women. CONCLUSIONS: This study demonstrates the importance of
      considering race/ethnicity and class together in relation to health outcomes.

PMID- 17199458
TI  - Secondary osteoporosis: are we recognizing it?
AB  - BACKGROUND: As a growing percentage of Americans will be reaching their elderly
      years in the next decade, the prevalence of osteoporosis and its effects will
      have an even greater impact on the healthcare system. Advancements in bone
      research and development of newer treatments have allowed for the establishment
      of more refined guidelines and a growing awareness of the need to prevent,
      screen, and diagnose osteoporosis. Thus, more women are now being screened with
      dual x-ray absorptiometry scans (DXA) than ever before. The importance of a true
      understanding of the test results obtained from such screening is paramount. In
      our institution, recommendations to consider a secondary evaluation are made by
      the DXA interpreters when the Z-score is low. Few, if any, studies have evaluated
      the rates of physician and patient adherence with specific recommendations
      provided on the bone density report. METHODS: To assess compliance with such
      recommendations provided in DXA interpretations, we investigated the number of
      ordering providers who actually pursued these advisements. RESULTS: We found that
      among providers ordering DXAs, primary care providers did not pursue
      recommendations to pursue a secondary workup as often as their subspecialty
      counterparts. We also found a significant amount of vitamin D
      deficiency/insufficiency and primary hyperparathyroidism in the population
      evaluated. CONCLUSIONS: Primary care providers should be further educated on
      treatable secondary causes of osteoporosis as opposed to an often reflexive
      response of prescribing a pharmacological antiresportive agent without other
      consideration.

PMID- 17199459
TI  - Comparison of SWAN and WISE menopausal status classification algorithms.
AB  - BACKGROUND: Classification of menopausal status is important for epidemiological
      and clinical studies as well as for clinicians treating midlife women. Most
      epidemiological studies, including the Study of Women's Health Across the Nation
      (SWAN), classify women based on self-reported bleeding history. METHODS: The
      Women's Ischemia Syndrome Evaluation (WISE) study developed an algorithm using
      menstrual and reproductive history and serum hormone levels to reproduce the
      menopausal status classifications assigned by the WISE hormone committee. We
      applied that algorithm to women participating in SWAN and examined
      characteristics of women with concordant and discordant SWAN and WISE
      classifications. RESULTS: Of the 3215 SWAN women with complete information at
      baseline (1995-1997), 2466 (76.7%) received concordant classifications (kappa =
      0.52); at the fifth annual follow-up visit, of the 1623 women with complete
      information, 1154 (72.7%) received concordant classifications (kappa = 0.57). At
      each time point, we identified subgroups of women with discordant SWAN and WISE
      classifications. These subgroups, ordered by chronological age, showed increasing
      trends for menopausal symptoms and follicle-stimulating hormone (FSH) and a
      decreasing trend for estrogen (p < 0.001). CONCLUSIONS: The WISE algorithm is a
      useful tool for studies that have access to blood samples for hormone data
      unrelated to menstrual cycle phase, with or without an intact uterus, and no
      resources for adjudication. Future studies may want to combine aspects of the
      SWAN and WISE algorithms by adding hormonal measures to the series of bleeding
      questions in order to determine more precisely where women are in the
      perimenopausal continuum.

PMID- 17199460
TI  - The impact of a brief obstetrics clinic-based intervention on treatment use for
      perinatal depression.
AB  - OBJECTIVE: The purpose of this study was to examine the association of prenatal
      depression screening and obstetrics clinician notification procedures with
      depression treatment use through 6 weeks postpartum. METHODS: An initial sample
      of 1298 women was screened for depression as part of routine clinical care at
      their first prenatal care appointment using the Edinburgh Postnatal Depression
      Scale (EPDS) at a university hospital obstetrics clinic in the United States.
      Women with an EPDS > 10 who agreed to participate in this longitudinal study
      completed assessments of depression and treatment use throughout pregnancy and
      through 6 weeks postpartum. Following screening and prior to their second
      prenatal visit, all women scoring > or = 10 on the EPDS received nurse-delivered
      depression feedback and referral, and all treating physicians were notified of
      the elevated EPDS status (i.e., > or = 10) of their patients. RESULTS: The
      majority (65%) of pregnant women with current major depressive disorder (MDD)
      were not receiving any depression treatment throughout the study period. Overall,
      women with EDPS > or = 10 who reported that their physician discussed depression
      with them (67%) were significantly more likely to seek treatment (compared with
      those who did not report physician discussion of depression with them) by the 1
      month prenatal follow-up but not by the 6 weeks postpartum follow-up. Initial
      depression severity and treatment use prior to screening were the strongest
      predictors of subsequent depression treatment use. CONCLUSIONS: Depression
      screening combined with systematic clinician follow-up showed a modest short-term
      impact on depression treatment use for perinatal depression but did not affect
      depression outcomes. Most women with MDD were not engaged in treatment throughout
      the follow-up period despite the interventions. More intensive and repeated
      monitoring might enhance the effect of clinician interventions to improve
      treatment use.

PMID- 17199461
TI  - Gender differences across race/ethnicity in use of health care among Medicare
      aged Americans.
AB  - BACKGROUND: Despite Medicare, medical services are not equally used by elderly
      women and men in the United States. Our purpose is to examine gender differences
      in healthcare utilization among older Americans, the persistence of gender
      differences across race/ethnicity, and the roles of sociodemographic, health, and
      economic factors to explain differences. METHODS: Data from the 1998-2000 Health
      and Retirement Study are used to investigate gender differences in use of
      hospital, outpatient surgery, home health, and physician services. Analyses are
      controlled for sociodemographic, health (medical conditions, functional health),
      and economic (income, wealth, education, health insurance) factors. RESULTS:
      Women are significantly less likely to use hospital service (odds ratio
      [OR]=0.83) and outpatient surgery (OR=0.85) but are more likely to use home
      health care (OR=1.27) and physician services (OR=1.45), controlling for
      sociodemographics. Differences in health needs and economic resources partially
      mediate the gender differences in physician and home healthcare utilization but
      do not explain the gender differences in hospital service and outpatient surgery.
      Notably, African American, Hispanic, and white women compared with men show
      significantly less use of hospital services. CONCLUSIONS: Gender differences in
      medical use vary according to the type of services used and are largely
      consistent across racial/ethnic groups. As the size of the Medicare population
      increases, promoting equitable use of healthcare resources by both women and men
      is an important issue in developing healthcare policy and designing public health
      strategies.

PMID- 17199464
TI  - Therapeutic blue light: a different ray of light on an age-old problem.

PMID- 17199462
TI  - Anger, hostility, and cardiac symptoms in women with suspected coronary artery
      disease: the Women's Ischemia Syndrome Evaluation (WISE) Study.
AB  - OBJECTIVE: To determine the relationship of anger and hostility to angiographic
      coronary artery disease (CAD), symptoms, and functional status among women with
      suspected CAD. METHODS: Data were collected from 636 women with suspected CAD
      referred for diagnostic angiography in the Women's Ischemia Syndrome Evaluation
      (WISE) Study. CAD was assessed as angiographic presence/absence of disease (> or
      =50% stenosis in any epicardial coronary artery). Hostility/anger, angina,
      symptoms, and functional status were assessed by the Cook-Medley Hostility
      Inventory, Spielberger Anger Expression Scale, cardiovascular symptom history,
      and the Duke Activity Status Index. RESULTS: Logistic regression revealed that
      anger-out (i.e., aggressive behavior in response to angry feelings) was
      independently associated with the presence/absence of angiographic CAD (OR =
      1.09, CI 1.01-1.17). Anger and hostility were higher among women reporting
      increased cardiovascular symptoms. In women without angiographic CAD, those with
      nonanginal cardiac symptoms had the highest anger-out, anger expression, hostile
      affect, and aggressive responding scores, and those with typical angina reported
      the lowest functional status. Among women with CAD, functional status was lowest
      in women with atypical angina. CONCLUSIONS: Among women with suspected CAD, anger
      out scores were associated with the presence of angiographic CAD. Anger/hostility
      traits were associated with increased symptoms, particularly with nonanginal
      chest pain in women without angiographic CAD. Relationships among psychosocial
      factors, cardiac symptoms, and angiographic CAD are potentially important in the
      management of women with suspected CAD.

PMID- 17199465
TI  - Effects of combined 405-nm and 880-nm light on Staphylococcus aureus and
      Pseudomonas aeruginosa in vitro.
AB  - OBJECTIVE: The aim of this study was to determine the effect of a combination of
      405-nm blue light and 880-nm infrared light on Staphylococcus aureus and
      Pseudomonas aeruginosa in vitro. BACKGROUND DATA: Reports indicate that certain
      wavelengths and treatment parameters of light promote the growth of bacteria, but
      our earlier study indicates that light at specific wavelengths and intensities
      are bactericidal for specific organisms (1). METHODS: Two common aerobes,
      Staphylococcus aureus and Pseudomonas aeruginosa were tested because of their
      frequent isolation from skin infections and wounds. Each organism was treated
      simultaneously with a combination of 405-nm and 880-nm light emitted by a cluster
      of Super Luminous Diodes (SLDs). Doses of 1, 3, 5, 10, and 20 Jcm2 were used.
      Colony counts were performed and compared to untreated controls using Student t
      tests and one-way ANOVA with Tukey and Scheffe post hoc analyses. RESULTS: The
      results revealed significant dose-dependent bactericidal effects of the combined
      blue and infrared light on Staphylococcus aureus (F 4,94 = 5.38, p = 0.001) and
      Pseudomonas aeruginosa (F 4,95 = 21.35, p < 0.001). With P. aeruginosa, the
      treatment reduced the number of bacteria colonies at all doses, achieving
      statistical significance at 1, 3, and 20 J cm2 doses and reducing bacterial
      colony by as much as 93.8%; the most effective dose being 20 J cm2. Irradiation
      of S. aureus resulted in statistically significant decreases in bacterial
      colonies at all dose levels; the most decrease, 72%, was also achieved with 20
      Jcm2. CONCLUSION: Appropriate doses of combined 405-nm and 880-nm phototherapy
      can kill Staphylococcus aureus and Pseudomonas aeruginosa in vitro, suggesting
      that a similar effect may be produced in clinical cases of bacterial infection.

PMID- 17199466
TI  - In vitro bactericidal effects of 405-nm and 470-nm blue light.
AB  - OBJECTIVE: The aim of this study was to determine the bactericidal effect of 405-
      and 470-nm light on two bacteria, Staphylococcus aureus and Pseudomonas
      aeruginosa, in vitro. BACKGROUND DATA: It is well-known that UV light kills
      bacteria, but the bactericidal effects of UV may not be unique since recent
      studies indicate that blue light produces a somewhat similar effect. The effects
      of blue light seem varied depending on wavelength, dose and the nature of the
      bacteria, hence this study. METHODS: Two common aerobes, Staphylococcus aureus
      and Pseudomonas aeruginosa, and anaerobic Propionibacterium acnes were tested.
      Each organism was treated with Super Luminous Diode probes with peak emission at
      405 and 470 nm. Treatment was timed to yield 1, 3, 5, 10, and 15 Jcm2 doses.
      Colony counts were performed and compared to untreated controls. RESULTS: The 405
      nm light produced a dose dependent bactericidal effect on Pseudomonas aeruginosa
      and Staphylococcus aureus (p < .05), achieving as much as 95.1% and nearly 90%
      kill rate for each, respectively. The 470-nm light effectively killed Pseudomonas
      aeruginosa at all dose levels, but only killed Staphylococcus aureus at 10 and 15
      J cm2. With this wavelength, as much as 96.5% and 62% reduction of Pseudomonas
      aeruginosa and Staphylococcus aureus was achieved, respectively. Neither of the
      two wavelengths proved bactericidal with anaerobic Propionibacterium acnes.
      CONCLUSION: The results indicate that, in vitro, 405- and 470-nm blue light
      produce dose dependent bactericidal effects on Pseudomonas aeruginosa and
      Staphylococcus aureus but not Propionibacterium acnes.

PMID- 17199467
TI  - Effects of 960-nm diode laser irradiation on calcium solubility of dental enamel:
      an in vitro study.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of 960 nm diode
      laser and acidulated phosphate fluoride on calcium solubility of human dental
      enamel. BACKGROUND DATA: Interest in diode lasers has grown steadily since its
      invention due to its inherent advantages and its range of applications. Several
      other laser types have shown good results in caries prevention; however, there
      are few studies on dental tissue interactions using diode lasers. METHODS: Acid
      resistance was evaluated using 65 enamel specimens, divided into five groups:
      control (C), fluoride (F), laser (L), laser + fluoride (LF), and fluoride + laser
      (FL). The laser was operated using the parameters of 6.5-W peak power, 5-msec
      pulse duration, 10-Hz repetition rate, and 33-mJ pulse energy. These parameters
      were previously tested regarding pulpal temperature rise and enamel morphology,
      and were determined to be safe. The amount of calcium lost during
      demineralization was measured. RESULTS: The calcium solubility of the laser group
      was 12% higher than of the control group (p > 0.05). Group F showed a 33.6%
      increase of acid resistance (p < 0.05). When laser was associated with fluoride,
      the calcium solubility increased significantly (p < 0.05) compared to both the
      control group and the laser group. Groups treated with fluoride showed the same
      results (p > 0.05). CONCLUSION: The 960-nm diode laser promoted a slight increase
      in calcium solubility. A statistically significant reduction on calcium
      solubility was achieved with the three treatments that involve fluoride (F, FL,
      and LF). The additional application of laser irradiation did not cause any
      significant increase or decrease in calcium solubility.

PMID- 17199468
TI  - Comparison of results of 500 microdiscectomies and 500 percutaneous laser disc
      decompression procedures for lumbar disc herniation.
AB  - OBJECTIVE: This article aimed to analyze the neurosurgical results of 500
      patients treated with microdiscectomies and 500 patients treated with
      percutaneous laser disc decompression. BACKGROUND DATA: It has been suggested in
      the literature that percutaneous laser disc decompression might be considered a
      serious and valid alternative to microdiscectomy in the treatment of patients
      with discogenic pain caused by herniated lumbar disc. METHODS: Patients with
      herniated discs were treated by microdiscectomy (n = 500) according to the Caspar
      technique, and patients with discogenic pain were treated with percutaneous laser
      disc decompression (n = 500) according to the Choy technique. The inclusion and
      exclusion criteria were the same for both groups of patients. Age, gender
      distribution, multiple levels involved, and associated pathologies were not
      statistically different. The results were evaluated for both groups with the
      MacNab criteria. The follow-up period was 2 years (+/-1 year). RESULTS: In the
      microdiscectomy group, 85.6% of patients (n = 428) had a good or excellent
      outcome; in the percutaneous laser disc decompression group, 83.8% of patients (n
      = 419) had a good or excellent outcome. Complications occurred in 2.2% (n = 11)
      in the microdiscectomy group and in 0% in the percutaneous laser disc
      decompression group. CONCLUSION: The analysis of results for the two groups
      supports the conclusion that percutaneous laser disc decompression is a safe,
      minimally invasive, and strong alternative treatment to microdiscectomy in
      patients affected by herniated discs.

PMID- 17199469
TI  - Pathological study of pulp treated with chemicals after Er:YAG laser preparation.
AB  - OBJECTIVE: The aim of this study was to clarify pulp reaction following cavity
      preparation with an Er:YAG laser and subsequent treatment with topically applied
      chemicals to achieve a high resin bond strength. BACKGROUND DATA: The application
      of chemicals has been found to effectively remove or reform the denatured layer
      produced by Er:YAG laser irradiation and has been proposed as a new strategy for
      improving resin bond strength. However, very little is known about pulp reaction
      to chemical procedures. METHODS: Class 5 dentin cavities were prepared with an
      Er:YAG laser in 128 teeth in nine adult dogs. The teeth were then coated with
      glutaraldehyde (GA group), or phosphoric acid and sodium hypochlorite (PA group)
      to reform or remove the denatured layer. All the cavities were then restored with
      composite resin. In the control group, no chemical application was carried out
      prior to restoration. The animals were sacrificed immediately after, and at 7 and
      90 days following treatment. The treated teeth were then extracted for
      histopathological examination of the pulp. RESULTS: Pathological evaluation of
      the pulp indicated a good condition in each group at each of the three
      observation time points. No bacterial growth was observed on the cavity walls or
      bacterial invasion into the dentinal tubules or pulp chambers in any of the
      groups at any of the observation periods. CONCLUSION: Our findings suggest that
      the application of chemicals to remove or reform denatured layers is effective in
      obtaining better composite resin restoration with no pulp damage.

PMID- 17199470
TI  - Effect of multiple exposures of low-level laser therapy on the cellular responses
      of wounded human skin fibroblasts.
AB  - OBJECTIVE: This study aimed to establish the behavior of wounded human skin
      fibroblasts (HSF) after heliumneon (HeNe) (632.8 nm) laser irradiation using one,
      two, or three exposures of different doses, namely, 2.5, 5.0, or 16.0 J/cm(2) on
      each day for 2 consecutive days. BACKGROUND DATA: Low-level laser therapy (LLLT)
      is a form of phototherapy used to promote wound healing in different clinical
      conditions. LLLT at than adequate wavelength, intensity, and dose can accelerate
      tissue repair. However, there is still conflicting information about the effect
      of multiple irradiations on the cellular responses of wounded cells. METHODS:
      Cellular responses to HeNe laser irradiation were evaluated by measuring changes
      in cell morphology, cell viability, cell proliferation, and damage caused by
      multiple irradiations. RESULTS: A single dose of 5.0 J/cm(2), and two or three
      doses of 2.5 J/cm(2) had a stimulatory or positive effect on wounded fibroblasts
      with an increase in cell migration and cell proliferation while maintaining cell
      viability, but without causing additional stress or damage to the cells. Multiple
      exposures at higher doses (16 J/cm(2)) caused additional stress, which reduces
      cell migration, cell viability, and ATP activity, and inhibits cell
      proliferation. CONCLUSION: The results show that the correct energy density or
      fluence (J/cm(2)) and number of exposures can stimulate cellular responses of
      wounded fibroblasts and promote cell migration and cell proliferation by
      stimulating mitochondrial activity and maintaining viability without causing
      additional stress or damage to the wounded cells. Results indicate that the
      cumulative effect of lower doses (2.5 or 5 J/cm(2)) determines the stimulatory
      effect, while multiple exposures at higher doses (16 J/cm(2)) result in an
      inhibitory effect with more damage.

PMID- 17199471
TI  - Microleakage of class V glass ionomer restorations after conventional and Er:YAG
      laser preparation.
AB  - OBJECTIVE: The aim of this study was to investigate the microleakage in class V
      cavities following Er:YAG laser or conventional preparation restored with two
      conventional glass ionomer cements (cGIC) and to evaluate the effect of
      conditioning on laser-prepared surfaces. BACKGROUND DATA: Information on this
      topic related to cGIC is scarce. METHODS: Sixty class V cavities were assigned to
      six groups: I and IV were Er:YAG-lased, II and V Er:YAG-lased and conditioned,
      and III and VI conventionally prepared and conditioned. Groups I, II, and III,
      were restored with Ketac Fil Plus Applicap; groups IV, V, and VI were restored
      with Fuji IX GP Capsule. Then, teeth were stored in distilled water (37 degrees
      C, 24 h), thermal cycled 1500 times (5-55 degrees C), placed in a 2% aqueous
      solution of methylene blue (37 degrees C, 24 h), embedded in acrylic resin,
      sectioned oro-facially, and analyzed for leakage. RESULTS: Statistically
      significant differences between occlusal and cervical regions were observed (p <
      0.05). Group III showed significantly more microleakage at the occlusal margin
      compared to group II (p = 0.022). Group V showed significantly more microleakage
      at the gingival margin than group VI (p = 0.022). Leakage on the occlusal margins
      was significantly higher in group III than in group VI (p = 0.038). Scanning
      electron microscopy indicated that conditioning of laser-prepared dentin with
      Ketac conditioner partially closed the tubules' orifices, whereas the use of GC
      conditioner completely obliterated the tubules. CONCLUSION: The application of
      Ketac Fil Plus to laser-prepared enamel and dentin resulted in a better and more
      reproducible seal compared to conventionally prepared tooth surfaces. When using
      the more viscous Fuji IX application, Er:YAG lasing did not improve marginal
      adaptation.

PMID- 17199472
TI  - Development of a surgical diode-laser system: controlling the mode of operation.
AB  - OBJECTIVE: The aim of this study was to develop a microcontroller based surgical
      diode laser system and to test it at two different modes (continuous [CW] and
      modulated) in vitro on lamb liver tissue. BACKGROUND DATA: In laser surgery,
      depending on the properties of laser source (wavelength, power, application time,
      and mode of operation), the effects observed on the tissue may change from
      carbonization to hyperthermia. The aim is to remove the target tissue without
      giving any thermal damage to the surrounding tissue. Carbonization should be
      avoided, thus controlling the mode of operation is very crucial. METHODS: The
      system consisted of a microcontroller based control unit, 980-nm high-power diode
      laser source, and fiber delivery unit. This system has the capability of
      delivering different modes of laser energy to the target tissue ranging from CW
      to 20-Hz modulated beams. The surgical diode laser system was tested on liver
      tissue in vitro. Efficiency of laser-tissue interaction was quantified in terms
      of thermal alteration per unit energy and corresponding carbonization level.
      RESULTS: Modulated mode resulted in larger coagulated area with minimum
      carbonizations. Carbonized area/thermally altered area (CarbA/TAA) ratio for CW
      mode of operation at 16 J is 0.35; however, this ratio was found to be 0.05 at
      modulated mode, when even 10 times higher energy (160 J) was delivered to the
      target tissue. CONCLUSION: Results emphasized the significance of mode of
      operation as well as the other laser parameters. Modulated mode was found to be a
      promising regime for safer laser surgery.

PMID- 17199473
TI  - Nd:YAG laser influence on microtensile bond strength of different adhesive
      systems for human dentin.
AB  - OBJECTIVE: The purpose of this study was to investigate the influence of Nd:YAG
      on microtensile bond strength (microTBS) of different adhesive systems for human
      dentin. BACKGROUND DATA: Lasers have been widely used in dentistry. New adhesive
      systems with different chemical compositions are introduced every year, and it is
      important to investigate the bonding of new adhesive systems to dentin irradiated
      with laser. METHODS: The occlusal surfaces of third molars were removed to obtain
      flat dentin surfaces. The teeth were randomly divided into six groups. Each
      adhesive system was applied, according to manufacturers' instructions, to surface
      dentine with and without Nd:YAG laser irradiation (0.9 W, 15 Hz, 60 mJ per
      pulse). A block of composite resin was built over the adhesive layer. The
      specimens were sectioned to obtain 0.70 x 0.70 mm of transversal section. Twenty
      test specimens were selected for each group, and were then submitted to microTBS
      on a universal testing machine. RESULTS: According to Student's t-test, for
      Single Bond, there was no statistically significant difference without (49.32
      MPa) and with (47.34 MPa) laser application (p = 0.60). For the Tyrian SPE/One
      Step Plus, microTBS value with laser (27.09 MPa) was statistically higher than
      without laser (19.13 MPa), as well as for Adper Prompt L-Pop (22.85 and 13.78
      Mpa; p < or = 0.01). CONCLUSION: The application of Nd:YAG laser to dentin
      provided an increase in the bond strength values for the Tyrian SPE/One Step Plus
      and Adper Prompt L-Pop adhesive systems, but did not influence the bond strength
      values of the Single Bond adhesive system.

PMID- 17199474
TI  - Comparative study of how low-level laser therapy and low-intensity pulsed
      ultrasound affect bone repair in rats.
AB  - OBJECTIVE: This study aimed to compare the consequences of low-level laser
      therapy (LLLT) and low-intensity pulsed ultrasound (LIPUS) on bone repair.
      BACKGROUND DATA: Many studies have assessed the effects of LLLT and LIPUS on bone
      repair, but a comparison of them is rare. METHODS: Male Wistar rats (n = 48) with
      tibial bone osteotomy were used. One group had the osteotomized limb treated with
      LLLT (GaAlAs laser, 780 nm, 30 mW, 112.5 J/cm(2)) and the second group with LIPUS
      (1.5 MHz, 30 mW/cm(2)), both for 12 sessions (five times per week); a third group
      was the control. After 20 days, rats were sacrificed and had their tibias
      submitted to a bending test or histomorphometric analysis. RESULTS: In the
      bending test, maximum load at failure of LLLT group was significantly higher (p <
      0.05). Bone histomorphometry revealed a significant increase in osteoblast number
      and surface, and osteoid volume in the LLLT group, and a significant increase in
      eroded and osteoclast surfaces in the LIPUS group. CONCLUSION: LIPUS enhanced
      bone repair by promoting bone resorption in the osteotomy area, while LLLT
      accelerated this process through bone formation.

PMID- 17199475
TI  - Effect of diode laser application with G-probe on ocular hypotony after
      trabeculectomy with mitomycin-C.
AB  - OBJECTIVE: The aim of this study was to assess the feasibility of a new technique
      to treat overfiltering blebs leading to hypotony after penetrating glaucoma
      surgery. BACKGROUND: There is no previous report on diode laser application with
      G-probe on ocular hypotony consequent to trabeculectomy with adjunctive mitomycin
      C. METHODS: This clinical trial was conducted on eight eyes of eight patients
      with hypotony after trabeculectomy with adjunctive mitomycin-C. Ten to 12 diode
      laser (810 nm) spots were applied by G-probe over the bleb area with 2000-2500 mw
      power and for 1500-2000 msec duration; if the bleb was thin, the laser was
      applied on its border. RESULTS: The mean age of patients was 29.1 +/- 12.4 years;
      two of them were female. Mean preoperative and postoperative intraocular pressure
      (IOPs) were 4.3 +/- 1.5 and 10.1 +/- 3.4 mm Hg, respectively (p = 0.017).
      Although the IOP increased in seven eyes (87.5%), the visual acuity increased >
      or =1 line in four (50%), remained stable in three (37.5%), and decreased 1 line
      in one (12.5%) after an average follow-up of 4 months. All of the blebs were
      notably smaller and pigmented. No complications occurred other than the need to
      start Timolol eye drops in one eye for controlling IOP and peaked pupil in two
      others. CONCLUSION: Diode laser application with G-probe appears to be a useful
      modality of treatment for ocular hypotony and overfiltering blebs resulting from
      trabeculectomy with mitomycin-C.

PMID- 17199476
TI  - Micromorphological analysis of dentinal structure after irradiation with Nd:YAG
      laser and immersion in acidic beverages.
AB  - OBJECTIVE: The purpose of this study was to analyze dentinal surfaces that were
      exposed to acidic beverages, then treated with Nd:YAG laser and afterwards
      exposed to acidic beverages again. BACKGROUND DATA: Dentin hypersensitivity can
      result from surface erosion caused by acidic beverages, which exposes and
      enlarges the dentinal tubules. Nd:YAG laser has been used as a treatment option.
      METHODS: Sixty-eight dentin samples were prepared and assigned to five groups:
      G1, control (n = 4); G2, 3-h immersion (n = 16); G3, 3-h immersion + Nd:YAG; G4,
      3-h immersion + Nd:YAG + 3-h immersion; and G5, 3-h immersion + Nd:YAG + 6-h
      immersion. Each group was divided into four subgroups, with different acid
      beverages: lemon (n = 4); passion fruit (n = 4); cola (n = 4); and wine (n = 4).
      Irradiation with the Nd:YAG was in contact mode, focused and perpendicular
      through a quartz fiber of 300 microm of diameter in scanning movements for 60 sec
      with a 10-sec interval and the paramenters 0.6 W, 10 Hz, 60 mJ, and 85 mJ/cm(2).
      Each subgroup was examined by scanning electron microscope. RESULTS: All the
      acidic beverages contributed to exposure and increased diameter of the dentinal
      tubules. CONCLUSIONS: Irradiation with Nd:YAG laser produced obliteration of and
      reduction in the number of dentinal tubules, thus modifying the original
      structure.

PMID- 17199477
TI  - Comparative study using 685-nm and 830-nm lasers in the tissue repair of
      tenotomized tendons in the mouse.
AB  - OBJECTIVE: The objective of this study was to evaluate the effects of 685- and
      830-nm laser irradiations, at different fluences on the healing process of
      Achilles tendon (Tendon calcaneo) of mice after tenotomy. BACKGROUND DATA: Some
      authors have shown that low-level laser therapy (LLLT) is able to accelerate the
      healing process of tendinuos tissue after an injury, increasing fibroblast cell
      proliferation and collagen synthesis. However, the mechanism by which LLLT acts
      on healing process is not fully understood. METHODS: Forty-eight male mice were
      divided into six experimental groups: group A, tenomized animals, treated with
      685 nm laser, at the dosage of 3 J/cm(2); group B, tenomized animals, treated
      with 685-nm laser, at the dosage of 10 J/cm(2); group C, tenomized animals,
      treated with 830-nm laser, at dosage of 3 J/cm(2); group D, tenomized animals,
      treated with 830-nm laser, at the dosage of 10 J/cm(2); group E, injured control
      (placebo treatment); and group F, non-injured standard control. Animals were
      killed on day 13 post-tenotomy, and their tendons were surgically removed for a
      quantitative analysis using polarization microscopy, with the purpose of
      measuring collagen fibers organization through the birefringence (optical
      retardation [OR]). RESULTS: All treated groups showed higher values of OR when
      compared to injured control group. The best organization and aggregation of the
      collagen bundles were shown by the animals of group A (685 nm, 3 J/cm(2)),
      followed by the animals of group C and B, and finally, the animals of group D.
      CONCLUSION: All wavelengths and fluences used in this study were efficient at
      accelerating the healing process of Achilles tendon post-tenotomy, particularly
      after the 685-nm laser irradiation, at 3 J/cm(2). It suggests the existence of
      wavelength tissue specificity and dose dependency. Further studies are required
      to investigate the physiological mechanisms responsible for the effects of laser
      on tendinuos repair.

PMID- 17199478
TI  - Standards for the design and conduct of systematic reviews with low-level laser
      therapy for musculoskeletal pain and disorders.

PMID- 17199479
TI  - Consensus agreement on the design and conduct of clinical studies with low-level
      laser therapy and light therapy for musculoskeletal pain and disorders.

PMID- 17199485
TI  - Hills recipe for nutrition: Scientific evidence. Clinical trials provide
      scientific basis for nutrition decisions.

PMID- 17199487
TI  - What is your diagnosis? Congenital hypothyroidism.

PMID- 17199486
TI  - Thoughts on the 2006 feline vaccine panel report.

PMID- 17199488
TI  - What is your diagnosis? Dorsomedial avulsion of the right second carpal bone with
      medial displacement of the proximal portion of the second metacarpal bone.

PMID- 17199489
TI  - Anesthesia case of the month. Hyperkalemic periodic paralysis.

PMID- 17199490
TI  - Systematic review of comparative studies examining alternatives to the harmful
      use of animals in biomedical education.
AB  - OBJECTIVE: To systematically review the published literature for controlled
      studies comparing learning outcomes of traditional methods that require the
      terminal use of animals (eg, dissection, live-animal surgery, and live-animal
      laboratory demonstrations) with outcomes obtained with alternative teaching
      methods. DESIGN: Systematic review. STUDY POPULATION: Controlled studies
      published between 1996 and 2004. PROCEDURES: PubMed was searched with the
      following keywords, used alone and in combination: educational alternatives,
      nonlethal teaching methods, veterinary alternatives, medical education, and
      nonterminal animal use. Cited references of retrieved reports were reviewed to
      identify additional reports. Reports were selected for review only if a
      comparison group was included. RESULTS: 17 studies that were randomized
      controlled trials or nonrandomized trials that included a comparison group were
      identified. Five involved veterinary students, 3 involved medical students, 6
      involved university undergraduate students, and 3 involved high school biology
      students. Sample size ranged from 14 to 283 students. Eleven studies appeared to
      be randomized, parallel-group trials, 4 involved comparative groups to which
      participants were not randomly assigned or for which the randomization process
      was not clear, 1 was a 2-period crossover study, and 1 involved a retrospective
      review of grades. In all 17 studies reviewed, results associated with the
      alternative method of instruction were not significantly different from or
      superior to results associated with the conventional method. CONCLUSIONS AND
      CLINICAL RELEVANCE: Although the number of controlled studies identified was
      small, the results seem to support more widespread adoption of alternative
      teaching methods in biomedical education.

PMID- 17199491
TI  - Epidural anesthesia with bupivacaine, bupivacaine and fentanyl, or bupivacaine
      and sufentanil during intravenous administration of propofol for
      ovariohysterectomy in dogs.
AB  - OBJECTIVE: To compare cardiovascular and systemic effects and analgesia during
      the postoperative period of epidural anesthesia performed with bupivacaine alone
      or with fentanyl or sufentanil in bitches maintained at a light plane of
      anesthesia with continuous infusion of propofol. STUDY DESIGN: Prospective
      randomized masked clinical trial. ANIMALS: 30 female dogs of various breeds.
      PROCEDURES: Dogs were allocated into 3 groups of 10 each. One group received
      fentanyl (2 microg/kg [0.91 microg/lb]) and bupivacaine (1 mg/kg [0.45 mg/lb]), 1
      group received sufentanil (1 microg/kg) and bupivacaine (1 mg/kg), and 1 group
      received bupivacaine (1 mg/kg). All dogs received acepromazine (0.1 mg/kg [0.045
      mg/lb]) and continuous infusion of propofol for sedation. The agents were
      administered into the lumbosacral space and diluted in saline (0.9% NaCl)
      solution to a total volume of 0.36 mL/kg (0.164 mL/lb). Cardiac and respiratory
      rates, arterial blood pressures, pH, and blood gases were evaluated. Analgesia,
      sedation level, serum cortisol concentrations, and plasma catecholamine
      concentrations were measured regularly for 6 hours. RESULTS: No important changes
      in cardiovascular, respiratory, or sedation variables were observed. Degree of
      analgesia in the postoperative period was higher in the sufentanil group,
      although use of fentanyl and bupivacaine also resulted in a sufficient level of
      analgesia. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the 3 anesthetic techniques
      permitted ovariohysterectomy with sufficient analgesia and acceptable
      neuroendocrine modulation of pain with minimal adverse effects.

PMID- 17199493
TI  - Response of feral cats to vaccination at the time of neutering.
AB  - OBJECTIVE: To determine whether administration of inactivated virus or modified
      live virus (MLV) vaccines to feral cats at the time of neutering induces
      protective serum antiviral antibody titers. DESIGN: Prospective study. ANIMALS:
      61 feral cats included in a trap-neuter-return program in Florida. PROCEDURES:
      Each cat received vaccines against feline panleukopenia virus (FPV), feline
      herpes virus (FHV), feline calicivirus (FCV), FeLV, and rabies virus (RV).
      Immediately on completion of surgery, vaccines that contained inactivated RV and
      FeLV antigens and either MLV or inactivated FPV, FHV, and FCV antigens were
      administered. Titers of antiviral antibodies (except those against FeLV) were
      assessed in serum samples obtained immediately prior to surgery and approximately
      10 weeks later. RESULTS: Prior to vaccination, some of the cats had protective
      serum antibody titers against FPV (33%), FHV (21%), FCV (64%), and RV (3%).
      Following vaccination, the overall proportion of cats with protective serum
      antiviral antibody titers increased (FPV [90%], FHV [56%], FCV [93%], and RV
      [98%]). With the exception of the FHV vaccine, there were no differences in the
      proportions of cats protected with inactivated virus versus MLV vaccines.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that exposure to FPV, FHV,
      and FCV is common among feral cats and that a high proportion of cats are
      susceptible to RV infection. Feral cats appeared to have an excellent immune
      response following vaccination at the time of neutering. Incorporation of
      vaccination into trap-neuter-return programs is likely to protect the health of
      individual cats and possibly reduce the disease burden in the community.

PMID- 17199494
TI  - Use of three-dimensional computed tomography for diagnosis and treatment planning
      for open-mouth jaw locking in a cat.
AB  - CASE DESCRIPTION: A 2.5-year-old spayed female Persian cat was evaluated for
      acute inability to close its mouth. CLINICAL FINDINGS: A wry-mouth malocclusion
      was evident, and the right side of the mandible was longer than the left side.
      The right mandibular tooth row appeared to be lowered. The lower jaw was
      persistently maintained in an open position. The presumptive diagnosis was open
      mouth jaw locking. Diagnostic imaging with computed tomography and 3-dimensional
      reconstruction was performed for definitive diagnosis and to achieve a better
      understanding of the lesions. Imaging revealed locking of the right ramus of the
      mandible, which was displaced ventrolaterally, causing the coronoid process to
      impinge on the right zygomatic arch. TREATMENT AND OUTCOME: A bilateral partial
      ostectomy of the rostroventral margins of the zygomatic arches with an autogenous
      fat graft implantation was performed. The cat recovered without complications and
      by the following morning was bright, alert, and responsive and eating canned cat
      food comfortably. One year after surgery, the owner reported that the cat had
      continued to function well, was eating normally, and had not had any observed
      locking episodes since surgery. CLINICAL RELEVANCE: Unlike radiographic imaging,
      computed tomography may be used to create 3-dimensional reconstructions of
      structures in cases of suspected open-mouth jaw locking; improve evaluation of
      the lesions; and improve decision-making and client education for diagnosis,
      treatment options, and prognosis.

PMID- 17199495
TI  - Indications, management, and outcome of long-term positive-pressure ventilation
      in dogs and cats: 148 cases (1990-2001).
AB  - OBJECTIVE: To determine outcome of positive-pressure ventilation (PPV) for 24
      hours or longer and identify factors associated with successful weaning from PPV
      and survival to hospital discharge in dogs and cats. DESIGN: Retrospective case
      series. ANIMALS: 124 dogs and 24 cats that received PPV for 24 hours or longer.
      PROCEDURES: Medical records were reviewed for signalment, primary diagnosis,
      reason for initiating PPV, measures of oxygenation and ventilation before and
      during PPV, ventilator settings, complications, duration of PPV, and outcome.
      Animals were categorized into 1 of 3 groups on the basis of the reason for PPV.
      RESULTS: Group 1 patients received PPV for inadequate oxygenation (67 dogs and 6
      cats), group 2 for inadequate ventilation (46 dogs and 16 cats), and group 3 for
      inadequate oxygenation and ventilation (11 dogs and 2 cats). Of the group 1
      animals, 36% (26/73) were weaned from PPV and 22% (16/73) survived to hospital
      discharge. In group 2, 50% (31/62) were weaned from PPV and 39% (24/62) survived
      to hospital discharge. In group 3, 3 of 13 were weaned from PPV and 1 of 13
      survived to hospital discharge. Likelihood of successful weaning and survival to
      hospital discharge were significantly higher for group 2 animals, and cats had a
      significantly lower likelihood of successful weaning from PPV, compared with
      dogs. Median duration of PPV was 48 hours (range, 24 to 356 hours) and was not
      associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested
      that long-term PPV is practical and successful in dogs and cats.

PMID- 17199496
TI  - Risk factors associated with outcome in dogs with tetanus: 38 cases (1987-2005).
AB  - OBJECTIVE: To assess the clinical course of disease and risk factors associated
      with outcome in dogs with tetanus. DESIGN: Retrospective case series. ANIMALS: 38
      dogs with tetanus. PROCEDURES: Data were collected from medical records of dogs
      with tetanus, including signalment; wound characteristics; initial clinical
      signs; severity of worst clinical signs; time to wound management, antimicrobial
      treatment, and antitoxin administration; and 28-day survival rate. Statistical
      analyses were performed to evaluate relationships between the potentially
      predictive variables and disease progression and outcome. RESULTS: The 28-day
      survival rate was 77% (among 35 uncensored dogs). The most common initial
      clinical signs in affected dogs were ocular (n = 18) and facial (11)
      abnormalities. Nineteen dogs progressed to recumbency with severe muscle spasms,
      and 14 dogs had high or low heart rate or blood pressure values. Eight dogs died
      or were euthanized because of complications of tetanus. There was a significant
      association between younger age and development of more severe clinical signs.
      Furthermore, a significant inverse relationship between development of severe
      clinical signs and survival was identified. There was no association between
      earlier initiation of wound management, antimicrobial administration, or
      antitoxin administration and either progression of signs or 28-day survival rate.
      Wound type was not associated with 28-day survival rate. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that younger dogs with tetanus may be more likely to
      develop severe clinical signs. The prognosis for survival in dogs with tetanus is
      good if abnormalities in heart rate or blood pressure values do not develop.

PMID- 17199497
TI  - Molecular identification of Phialophora oxyspora as the cause of mycetoma in a
      horse.
AB  - CASE DESCRIPTION: An 18-year-old mare was evaluated for an oral mass that
      developed after extraction of a broken incisor. CLINICAL FINDINGS: An ulcerated,
      firm, darkly pigmented, approximately 5-cm-diameter spherical mass involved the
      gingiva lateral and dorsal to the right first to third maxillary incisors.
      Osteolysis of the roots of the first and second right maxillary incisors and
      periosteal proliferation of the adjacent premaxilla margins were apparent on
      radiographs. Histologic examination of the mass revealed multiple coalescing and
      ramifying foci of abscess formation, each containing a well-defined, discrete,
      black mass (2 to 7 mm in diameter). Myriad fungal hyphae enmeshed in a black,
      granular, cementlike material were within each of the black structures. Mycetoma
      was the histologic diagnosis. The causative agent could not be identified via
      culture because of lack of distinguishing characteristics. Fungal DNA was
      isolated from frozen fungal cultures and paraffin sections. The D1/D2 domains of
      the large subunit P gene rDNA were amplified and sequenced. The sequences of the
      D1/D2 domains of both isolates were 96% homologous with those of Phialophora
      oxyspora. TREATMENT AND OUTCOME: The mass was surgically excised, the local area
      curetted, and the wound allowed to heal by second intention. Postoperative
      treatment consisted of administration of phenylbutazone and IV administration of
      sodium iodide followed by oral administration of potassium iodide. There was no
      evidence of recurrence 1 year later. CLINICAL RELEVANCE: Mycetomata should be a
      differential diagnosis for equine gingival masses. Identification of the fungal
      agent can be critical for selection of optimal treatments. Molecular methods may
      permit definitive identification when standard phenotypic-based identification
      criteria are inconclusive.

PMID- 17199498
TI  - Evaluation of the efficacy of prophylactic hoof health examination and trimming
      during midlactation in reducing the incidence of lameness during late lactation
      in dairy cows.
AB  - OBJECTIVE: To assess the efficacy of prophylactic hoof health examination and
      trimming during midlactation at reducing the incidence of lameness during late
      lactation in dairy cows. DESIGN: Randomized field trial. ANIMALS: 333 Holstein
      cows. PROCEDURES: Cows without apparent lameness were randomly allocated into 1
      of 2 groups approximately 204 days after calving. Cows allocated to the treatment
      group (n = 161) were examined on a tilt table for diagnosis and underwent hoof
      trimming procedures, if needed, for treatment of hoof disorders or lesions. Cows
      in the control group (n = 172) were not examined. Cows were assigned a locomotion
      score weekly for 28 weeks after allocation to a group. The number of cows
      classified as lame during late lactation (approx 205 to 400 days after calving)
      was compared between groups to assess the efficacy of prophylactic examination
      and trimming. RESULTS: Incidence of lameness during late lactation was 24% in
      cows in the control group and 18% in cows in the treatment group. CONCLUSIONS AND
      CLINICAL RELEVANCE: The 25% decrease in number of new cases of lameness in cows
      undergoing prophylactic hoof health examination and trimming during midlactation
      may be relevant for the well-being of dairy cows and should not represent a major
      economic burden to producers.

PMID- 17199500
TI  - Serum biochemical abnormalities in goats with uroliths: 107 cases (1992-2003).
AB  - OBJECTIVE: To characterize serum biochemical abnormalities in goats with
      uroliths. DESIGN: Retrospective case-control series. ANIMALS: 107 male goats with
      uroliths and 94 male goats with various nonrenal diseases (controls). PROCEDURES:
      For male goats, results of serum biochemical analyses collected from 1992 through
      2003 were retrieved from computerized records, as were signalment, clinical
      diagnoses, and discharge status. Results of analyses for BUN, creatinine,
      phosphorus, calcium, Na, K, Cl, total CO2, anion gap, and glucose were compared
      between goats with uroliths and control goats. RESULTS: Goats with uroliths had
      higher mean BUN, creatinine, total CO2, K, and glucose concentrations and lower
      mean phosphorus, Na, and Cl concentrations than control goats, with no difference
      in mean calcium concentration and anion gap. Goats with uroliths had higher
      frequency of azotemia, hypophosphatemia, hypochloridemia, and increased total CO2
      and lower frequency of decreased total CO2 than control goats. Urolithiasis
      occurred more frequently in castrated males than in sexually intact males and in
      dwarf African breeds than in other breeds. CONCLUSIONS AND CLINICAL RELEVANCE:
      Goats with uroliths often had hypophosphatemia at admission. Hypochloridemic
      metabolic alkalosis was the most common acid-base disorder. Rupture in the
      urinary tract system was associated with increased prevalence of hyponatremia and
      hyperkalemia. Clinicians should be aware of these abnormalities when determining
      fluid therapy.

PMID- 17199499
TI  - Eimeria macusaniensis infection in 15 llamas and 34 alpacas.
AB  - CASE DESCRIPTION: 15 llamas and 34 alpacas between 3 weeks and 18 years old with
      fecal oocysts or intestinal coccidial stages morphologically consistent with
      Eimeria macusaniensis were examined. Nineteen of the camelids were admitted dead,
      and 30 were admitted alive. Camelids admitted alive accounted for 5.5% of all
      camelid admissions during this period. CLINICAL FINDINGS: Many severely affected
      camelids had signs of lethargy, weight loss, decreased appetite, and diarrhea.
      Camelids with clinical infection also commonly had evidence of circulatory shock,
      fat mobilization, and protein loss. Nonsurviving camelids also had evidence of
      shock, edema, bile stasis, renal insufficiency, hepatic lipidosis, muscle damage,
      relative hemoconcentration, and sepsis. Postmortem examination frequently
      revealed complete, segmental replacement of the mucosa of the distal portion of
      the jejunum with coccidial meronts and gamonts. For 17 of 42 camelids, results of
      initial fecal examinations for E macusaniensis were negative. TREATMENT AND
      OUTCOME: Most camelids admitted alive were treated with amprolium hydrochloride,
      plasma, and various supportive treatments. Fifteen of the 30 treated camelids
      died or were euthanized. CLINICAL RELEVANCE: Findings suggest that E
      macusaniensis may be an important gastrointestinal tract pathogen in camelids of
      all ages. Clinical signs were frequently nonspecific and were often evident
      before results of fecal examinations for the parasite were positive. As with
      other coccidia, severity of disease was probably related to ingested dose, host
      immunity, and other factors. The clinical and herd relevance of positive fecal
      examination results must be determined.

PMID- 17199501
TI  - An interview with Stephen D. O'Connor, Ph.D. CEO, Nanostream, conducted by
      Glaser, Vicki.

PMID- 17199503
TI  - Real-time analysis of enzyme kinetics via micro parallel liquid chromatography.
AB  - A generic method for real-time monitoring of enzyme kinetics is described in this
      paper. This approach enables rapid development of assays for high-throughput
      screening or reaction monitoring in the linear range of the enzyme kinetic curve.
      In this paper, we used protein kinase A and kemptide (a well-studied assay
      system) to demonstrate assay optimization by using micro parallel liquid
      chromatography. The optimal substrate and enzyme concentrations were determined
      rapidly and conveniently compared with the traditional methods for determining
      these parameters. Additionally, the data collected from the same experiment
      permitted calculations of K (m) for the substrate, V (max), and time-course
      study. In general, this approach provides two advantages. First, the broad ranges
      of detectable product conversions facilitate selection and implementation of
      assay conditions for high-throughput screening. Second, the system permits
      determination of 50% inhibitory concentration values at less than 1% conversion
      of substrate to product, thereby validating screening hits in the linear range of
      the enzyme kinetic curve. Overall, this optimization process can be done in less
      than 8 h. To demonstrate the ability to monitor a wide range of assay conditions,
      we varied initial concentrations over eight orders of magnitude within a single
      experiment. Compared with a classical enzyme kinetics study, this method
      significantly speeds the target validation process and reduces time associated
      with assay development and high-throughput screening implementation.

PMID- 17199504
TI  - Configuration of a scintillation proximity assay for the activity assessment of
      recombinant human adenine phosphoribosyltransferase.
AB  - Adenine phosphoribosyltransferase plays a role in purine salvage by catalyzing
      the direct conversion of adenine to adenosine monophosphate. The involvement of
      the purine salvage pathway in tumor proliferation and angiogenesis makes adenine
      phosphoribosyltransferase a potential target for oncology drug discovery. We have
      expressed and characterized recombinant, N-terminally His-tagged human adenine
      phosphoribosyltransferase. Two assay formats were assessed for use in a high
      throughput screen: a spectrophotometric-based enzyme-coupled assay system and a
      radiometric ionic capture scintillation proximity bead assay format. Ultimately,
      the scintillation proximity assay format was chosen because of automated
      screening compatibility limitations of the coupled assay. We describe here the
      biochemical characterization of adenine phosphoribosyltransferase and the
      development of a robust, homogeneous, 384-well assay suitable for high throughput
      screening.

PMID- 17199505
TI  - Improved homogeneous proximity-based screening assay of potential inhibitors of
      17beta-hydroxysteroid dehydrogenases.
AB  - 17beta-Hydroxysteroid dehydrogenases (17beta-HSDs) are substrate- and tissue
      specific isoenzymes that regulate activation and inactivation of steroid
      hormones. Up-regulation and downregulation in expression of 17beta-HSDs are
      linked to onset of many steroid-dependent diseases, such as colon, prostate, and
      breast cancer; thus 17beta-HSDs are potential drug screening targets. Currently
      their enzymatic activities are usually measured using laborious chromatographic
      separations followed by radioactive detection of substrate and product. We have
      previously reported the use of a homogeneous luminescence resonance energy
      transfer-based immunoassay for 17beta-estradiol in screening of potential
      inhibitors of 17beta-HSD type 1 (17beta-HSD-1). By replacing the previously used
      cell-based enzyme reactions with recombinant enzyme reactions the sensitivity of
      the screening assay improved considerably. In addition, the single assay was able
      to detect the influence of a tested compound not only on 17beta-HSD-1 but also on
      17beta-HSD type 2 (17beta-HSD-2), catalyzing the opposite reaction. The screening
      results of the tested molecules obtained from the optimized immunoassay were very
      similar when compared with the results of high performance liquid chromatography
      separation analysis. The Z factors were 0.79 and 0.83 for 17beta-HSD-1 and 17beta
      HSD-2 assays, respectively. Thus the immunoassay measuring samples converted with
      the recombinant enzymes was a very suitable method for primary high throughput
      screening, and it could be used also in further characterization of potential
      drugs.

PMID- 17199506
TI  - A simple cell-based HTS assay system to screen for inhibitors of p53-Hdm2 protein
      protein interactions.
AB  - Green fluorescent protein-assisted readout for interacting proteins (GRIP) is a
      universal protein interaction discovery system that can be used to generate truly
      high throughput screening-compatible cellular assays to be used to screen for
      inhibitors of protein-protein interactions. The technology uses a "bait and prey"
      principle based on the distinct translocation behavior of the human cyclic AMP
      phosphodiesterase 4A4. Here we use the p53-Hdm2 Redistribution assay (Fisher
      BioImage ApS, Soborg, Denmark) as an example to describe the GRIP technology. The
      p53-Hdm2 Redistribution assay is a high content imaging assay based on the GRIP
      technology that is designed to measure the interaction between Hdm2 and the tumor
      suppressor p53. Hdm2 regulates p53 and inhibits its function by modulating its
      transcriptional activity and stability. Activation of p53 in tumor cells through
      inhibition of its physical interaction with Hdm2 is therefore a focus of cancer
      drug discovery. We have performed a pilot screen by screening 3,165 compounds
      from a diverse small-molecule library for inhibitors of the p53-Hdm2 interaction
      by using the p53-Hdm2 Redistribution assay. Here we show that by taking advantage
      of the translocation behavior of nonbound p53, it is possible to identify true
      inhibitors of the p53-Hdm2 interaction by extracting high content information
      from the acquired images.

PMID- 17199507
TI  - A nonadherent cell-based HTS assay for N-type calcium channel using calcium 3
      dye.
AB  - The N-type calcium channel is a member of the voltage-sensitive calcium channel
      family and plays a major role in the regulation of neurotransmitter release in
      the central and peripheral nervous systems. Inhibition of the N-type calcium
      channel by intrathecal administration of the channel-specific blocker omega
      conotoxin MVIIA (ziconotide) is efficacious in the treatment of severe chronic
      pain. While no orally active small molecules that block the N-type calcium
      channel are currently available, the discovery of such potentially valuable
      therapeutics would benefit from a reliable, high throughput assay. However, the
      assay of N-type calcium channel activity by measuring calcium influx using
      nonadherent cells in a high throughput fashion has not been achieved before,
      likely owing to a number of technical hurdles. For example, the measurement of
      calcium levels in nonadherent cells using conventional calcium indicators, such
      as Fluo-3 or Fluo-4, requires dyeloading the cells in suspension and subsequent
      removal of extracellular dye. This limits plate throughput and requires constant
      handling of the cells. To assay the N-type calcium channel activity using a
      nonadherent cell line in a high throughput manner, we investigated the
      application of no-wash calcium assay kits from Molecular Devices Corp.
      (Sunnyvale, CA): FLIPR Calcium, FLIPR Calcium Plus, and FLIPR Calcium 3. We show
      here that the FLIPR Calcium 3 assay kit can be used with nonadherent IMR-32 cells
      to measure potassium-evoked, omega-conotoxin MVIIA-reversible calcium flux with
      high throughput (15,000 data points/day), high quality (Z approximately 0.6), and
      minimal handling of the cells. Thus, this assay can be used to reliably and
      efficiently screen large compound libraries in the search for small molecule N
      type calcium channel blockers.

PMID- 17199508
TI  - Investigating cytoskeletal alterations as a potential marker of retinal and lens
      drug-related toxicity.
AB  - Actin filaments play a critical role in the normal physiology of lenticular and
      retinal cells in the eye. Disruption of the actin cytoskeleton has been
      associated with retinal pathology and lens cataract formation. Ocular toxicity is
      an infrequent observation in drug safety studies, yet its impact to the drug
      development process is significant. Recognizing compounds through screening with
      a potential ocular safety liability is one way to prioritize development
      candidates while reducing development attrition. Lens epithelial cells from
      human, dog, and rat origins and retinal pigmented epithelium cells from human,
      monkey, and rat origins were cultured and investigated with immunocytochemical
      techniques. Cells were treated using noncytotoxic doses of the compound, fixed,
      stained for actin with rhodamine phalloidin, and counterstained for nuclei with
      TOTO-3, followed by confocal imaging. Tamoxifen and several experimental
      compounds known to be in vivo lens and retinal toxicants caused a reduction in F
      actin fluorescence at noncytotoxic concentrations in all cells tested as observed
      by confocal microscopy. Developing an assay that predicts ocular toxicity helps
      the development process by prioritizing compounds for further investigation. Drug
      induced cytoskeletal alterations may be useful as a potential safety-screening
      marker of retinal and lens toxicity. The knowledge of actin molecular biology and
      the application of other mechanistic screens to toxicology are discussed.
      Reducing this work to a high-throughput platform will enable chemists to select
      compounds with a reduced risk of ocular toxicity.

PMID- 17199509
TI  - Relative quantitation of protein-protein interaction strength within the yeast
      two-hybrid system via fluorescence beta-galactosidase activity detection in a
      high-throughput and low-cost manner.
AB  - The yeast two-hybrid (Y2H) method is capable of delivering vast amounts of
      interacting positive yeast colonies from a single library screen, particularly if
      a multifunctional protein is used as bait. However, the selection of definitive
      colonies for further molecular analysis is limited by both technical practicality
      and high costs. Here we demonstrate a cost-effective and simple method for the
      rapid selection and ranking of those Y2H-positive interaction clones that are
      suitable for further analysis. We performed a Y2H screen for the identification
      of human transforming growth factor beta2- interacting proteins in a human skin
      keratinocyte library. The identified clones were ranked by the amount of beta
      galactosidase enzyme produced, as well as by the interaction strength of the
      positive colonies. The combination of high-throughput microplate fluorescence
      readers and specific fluorescence assays can be utilized for relative
      quantitation of protein-protein interaction strength of Y2H-positive colonies in
      crude yeast-cell lysates. We demonstrate here that the high sensitivity of the
      fluorescence approach can bypass cumbersome conventional methods of cell lysis
      used in beta-galactosidase assays, and still deliver accurate values for analysis
      of protein interaction data. Finally, we also achieved a better understanding of
      general aspects of beta-galactosidase measurements in the Y2H system, such as
      protein normalization, the influence of yeast culture incubation time on optimal
      beta-galactosidase detection, and the linearity of beta-galactosidase detection
      in crude cell lysates.

PMID- 17199510
TI  - Automated Tecan programming for bioanalytical sample preparation with EZTecan.
AB  - This paper reports the first successful automated Tecan (Tecan US, Research
      Triangle Park, NC) programming for bioanalytical sample analysis with an in-house
      developed software, called EZTecan. Based on the sample run list in the Watson
      Laboratory Information Management System (InnaPhase Corp., Philadelphia, PA),
      EZTecan can generate a Tecan program for bioanalytical sample preparation,
      including sample transfer, sample dilution, extraction, and reconstitution. Many
      built-in functions for EZTecan ensure the flexibility, quality, and efficiency of
      the liquid handling. It takes about 90 min to prepare two 96-well plates from
      sample transfer to reconstitution. Analytical results shown good inter- and intra
      assay accuracy and precision, which meet the +/-15% Good Laboratory Performance
      acceptance criteria. With EZTecan, bioanalysts can prepare samples without
      writing a single line of Tecan program.

PMID- 17199513
TI  - Foodborne disease trends and reports.

PMID- 17199514
TI  - Listeria monocytogenes in multiple habitats and host populations: review of
      available data for mathematical modeling.
AB  - Listeria monocytogenes has the ability to survive and multiply in diverse
      habitats and to cause infection in a variety of animal species and humans. We
      evaluated the literature on survival and multiplication within and transmission
      among multiple host populations and habitats, including man, sewage, general
      environment (soil, water, and vegetation), silage (fermented plant material),
      animals (including wild and domestic animals), and food processing plants. The
      available knowledge on L. monocytogenes transmission dynamics was translated into
      the key process nodes of interrelated host- and habitat-specific mathematical
      models, providing a starting framework for future modeling work and the ultimate
      development of a system-wide model for evaluation of its transmission, and
      strategies to reduce human exposure. Because of the ability of L. monocytogenes
      to survive and multiply in many habitats and hosts, and the number of possible
      transmission routes, it is highly unlikely that it could be eradicated from any
      habitat or host, including man. However, L. monocytogenes load within and
      transmission among habitats and host populations could probably be reduced. Based
      on the published information, we hypothesize that three recent anthropogenic
      practices increase the load within and transmission among reviewed habitats and
      host populations: extended refrigerated storage of ready-to-eat foods allowing L.
      monocytogenes growth in foods that are contaminated during production or
      subsequent handling; feeding domestic ruminants with silage often contaminated
      with L. monocytogenes; and dispersal of contaminated products of sewage treatment
      to agricultural fields and waters. Future mathematical modeling work could test
      how much the reduction of L. monocytogenes load and transmission in hosts and
      habitats associated with these anthropogenic practices would reduce human
      exposure and consequently human listeriosis.

PMID- 17199515
TI  - Development and evaluation of a real-time FRET probe based multiplex PCR assay
      for the detection of prohibited meat and bone meal in cattle feed and feed
      ingredients.
AB  - A novel real-time fluorescent multiplex polymerase chain reaction (PCR) assay for
      detecting and discriminating between bovine, ovine, and caprine contaminates in
      cattle feed was developed that simultaneously performs quality control monitoring
      on both the DNA extraction process and the level of PCR inhibition in the final
      DNA extract in a single PCR run. The assay used a single set of primers and two
      sets of FRET probes targeting the ruminant-specific mitochondrial cytochrome b
      gene. An internal control PCR reaction targeting a region of the chloroplast RNA
      polymerase beta-subunit (rpobeta) gene, which is conserved among plants, was
      incorporated into the ruminant multiplex PCR reaction in order to both monitor
      the DNA extraction method and to test for the presence of PCR inhibitors. The
      detection limit for bovine and ovine contaminates was evaluated over a period of
      two sets of six trials on 15 different types of cattle feed and feed ingredients
      spiked with known concentrations of bovine meat and bone meal (BMBM) and lamb
      meat and bone meal (LMBM). The assay was able to detect 0.05% w/w BMBM
      contamination and 0.1% w/w LMBM contamination in all samples of cattle feed and
      feed ingredients tested.

PMID- 17199516
TI  - Evaluation of effects of primary and secondary enrichment for the detection of
      Listeria monocytogenes by real-time PCR in retail ground chicken meat.
AB  - A SYBR Green I based real-time PCR assay with inlA-specific oligonucleotide
      primers was developed for easy and rapid detection of Listeria monocytogenes in a
      model food that usually has a high incidence of contamination with this pathogen.
      Results with pure cultures and artificially contaminated chicken meat samples
      indicate that the PCR assay was highly specific and sensitive. The melting point
      analysis of the 160 bp amplified DNA fragment was different for L. monocytogenes
      isolates of the two major phylogenetic divisions of the species, 1 and 2. The
      assay was then used to survey retail ground chicken meat for contamination with
      L. monocytogenes. Thirty-seven samples were enriched according to the United
      States Department of Agriculture culture assays to detect L. monocytogenes on
      meat. The use and efficiency of PCR assay was examined following both primary and
      secondary enrichments, which were also plated on chromogenic agar for enumeration
      of L. monocytogenes and nonpathogenic Listeria spp. to investigate the
      discrepancies between culture and PCR. Overall, L. monocytogenes was detected in
      75% of the samples. Primary enrichment yielded detection rates of 70% and 37% for
      culture and PCR, respectively. The corresponding rates for secondary enrichment
      were 54% and 70%, respectively. Test sensitivity is therefore influenced by the
      type of enrichment and is probably related not only to the limited growth of L.
      monocytogenes in the primary enrichment media (false-negative PCR results), but
      also to the high populations of nonpathogenic Listeria spp. in the secondary
      enrichment broths (false-negative culture results). The main challenge of rapid
      PCR-based detection of L. monocytogenes from food is the poor sensitivity of
      primary enrichment media. The improvement of enrichment conditions may help
      increase assay sensitivity.

PMID- 17199517
TI  - Analysis of fecal microbial flora for antibiotic resistance in ceftiofur-treated
      calves.
AB  - To evaluate the impact of ceftiofur treatment in calves on fecal shedding of
      ceftriaxone-resistant bacteria, 3 female Holstein dairy calves were treated by
      intramuscular injection with EXCENEL RTU (ceftiofur hydrochloride, Pharmacia and
      Upjohn) at a therapeutic dosage of 2.2 mg/kg/day for 5 consecutive days following
      label directions. Three untreated calves were housed separately and served as
      controls. One to 3 days following the initial administration of ceftiofur, there
      was a 14% and 2% increase of fecal bacteria resistant to 16 and 64 microg
      ceftriaxone/mL, respectively. This response remained unchanged from days 6 to 13,
      and increased resistance was seen at day 17. Randomly selected isolates of gram
      positive and gram-negative bacteria with elevated resistance to ceftriaxone
      (minimal inhibitory concentration (MIC) >or=64 microg ceftriaxone/mL) were
      isolated from calf feces and identified. In vitro conjugation experiments
      revealed that both the ceftriaxone-resistance gene bla (CMY-2) and class 1
      integron were transferred from two bacterial species to Salmonella spp. at a
      frequency of 10(7) to 10(5). MIC data revealed that Salmonella transconjugants
      acquired either reduced susceptibility or resistance to ceftriaxone as well as to
      multiple antibiotics. This genetic transfer occurred both within and between
      genera. Treatment of calves with therapeutic dosages of ceftiofur can
      significantly increase for at least 17 days following the initial treatment the
      fecal excretion of ceftriaxone-resistant bacteria, including Salmonella species.

PMID- 17199518
TI  - Molecular characterization and antibiotic resistance profiling of Salmonella
      isolated from retail Turkey meat products.
AB  - Contaminated poultry meat has been identified as one of the principal foodborne
      sources of Salmonella. Molecular characterization of Salmonella is important in
      addressing methods to control this pathogen. Seventy-four retail turkey meat
      samples were collected from various stores in Fargo, North Dakota in the fall of
      2003. Salmonella was recovered from 30 samples using the standard conventional
      culture method (FSIS, USDA). Isolated Salmonella were characterized by
      serotyping, pulsed-field gel electrophoresis (PFGE) analysis, plasmid analysis,
      and antibiotic resistance profiling. Five serotypes were identified among the
      isolates: Newport (n = 12), Hadar (n = 8), Heidelberg (n = 7), 4,12:nonmotile (n
      = 2), and Reading (n = 1). XbaI PFGE analysis revealed 13 PFGE types and
      succeeded in grouping the isolates according to their serotypes. Plasmid
      profiling identified 5 plasmid types (with 1 or 2 plasmids) among eleven isolates
      that harbored plasmids. Seventeen isolates were resistant to antibiotics. The
      Heidelberg serotype showed resistance to multiple antibiotics: 1 isolate had
      resistance to gentamicin, sulfamethoxazole, and streptomycin, and 6 isolates had
      resistance to tetracycline, gentamycin, sulfamethoxazole, kanamycin, and
      streptomycin. The Hadar serotype isolates were resistant to 2 or 3 antibiotics:
      tetracycline and streptomycin (1 isolate); tetracycline and kanamycin (1
      isolate); and tetracycline, kanamycin, and streptomycin (6 isolates). The
      4,12:nonmotile serotype isolates showed resistance to tetracycline only. The
      Newport and the Reading serotypes were susceptible to all 16 of the
      antimicrobials tested.

PMID- 17199519
TI  - Survival and recovery of Salmonella enterica serovar Typhimurium DT104 at low
      temperature and water activity in a broth system.
AB  - This study investigated the survival of Salmonella enterica serovar Typhimurium
      DT104 in a broth system under conditions of low temperature (4 degrees C) and low
      water activity (aw, 0.92 to 0.96). Incubation under these conditions resulted in
      significant reductions in the viability of stationary phase cells, determined by
      direct plating on selective XLD medium. Reductions in viable numbers were related
      to injury associated with initial osmotic shock (hyperosmosis) and further injury
      associated with longer-term storage under the above conditions. Such injured
      cells were, however, capable of recovering on a nonselective medium (TSA) and
      contributing to overall viable cell numbers in nonselective post-storage
      conditions. Storage at more extreme conditions, at lower aw values, led to cell
      death at rates influenced by storage temperature. Finally, the data obtained are
      considered in relation to pathogen survival on the surfaces of beef carcasses
      during chilling.

PMID- 17199520
TI  - Human lysozyme expressed in the mammary gland of transgenic dairy goats can
      inhibit the growth of bacteria that cause mastitis and the cold-spoilage of milk.
AB  - The addition of human milk components with intrinsic antimicrobial activity to
      livestock milk by genetic engineering has the potential to benefit milk safety
      and production as well as the health of the lactating animal. As a model for the
      dairy cow, we generated transgenic goats that expressed human lysozyme in their
      milk at 68% of the levels found in human milk. Milk from these transgenic animals
      had a bacteriostatic effect on both in vitro and in vivo growth of several
      microorganisms important to the dairy industry. In vitro, milk from transgenic
      animals was capable of slowing the growth of mastitis-causing strains of
      Escherichia coli (P < 0.02) and Staphylococcus aureus (P < 0.05) as well as the
      cold-spoilage organism Pseudomonas fragi (P < 0.02). The growth of an organism
      involved in cheese-making, Lactococcus lactis, was not affected by the presence
      of lysozyme in milk. The supplementation of control milk with purified lysozyme
      did not achieve the same inhibitory effect as milk from transgenic animals. In
      vivo, milk from transgenic animals supported less bacterial growth than control
      milk. This transgenic model demonstrates the possibilities offered by genetic
      engineering to enhance the antimicrobial nature of milk and the udder.

PMID- 17199521
TI  - Effect of an efflux pump inhibitor on the function of the multidrug efflux pump
      CmeABC and antimicrobial resistance in Campylobacter.
AB  - CmeABC, a multidrug efflux pump, contributes to the resistance of Campylobacter
      to a broad range of antimicrobials. We hypothesize that an efflux pump inhibitor
      (EPI) may inhibit the function of CmeABC and control antibiotic resistance in
      Campylobacter. In this study, we examined the effect of EPI Phe-Arg beta-naphthyl
      amide dihydrochloride (MC-207,110) on the susceptibility of Campylobacter to
      various antimicrobials. The presence of the EPI resulted in a 2- to 2048-fold
      reduction in the minimum inhibitory concentration (MIC) of antimicrobials known
      to be substrates of the CmeABC pump in all Campylobacter strains. Both intrinsic
      and acquired resistance of C. jejuni to erythromycin was decreased drastically
      (64- to 128-fold reduction in the MIC) in the presence of the EPI while the MICs
      of fluoroquinolones were only slightly decreased (2- to 4-fold). Examination of
      57 Campylobacter isolates from various origins further demonstrated that MC
      207,110 decreased the MICs of erythromycin (2- to 512-fold) in all isolates.
      Compared to wild-type strains, the isogenic CmeB mutants displayed smaller
      magnitudes of reduction in the MICs of antimicrobials in the presence of the EPI,
      indicating the inhibitory effect of the EPI is primarily CmeABC-dependent. The
      inhibitory effect of MC-207,110 was also dose-dependent, and as little as 0.5
      microg/mL of the EPI resulted in a decreased MIC for erythromycin in C. jejuni.
      More importantly, the presence of MC-207,110 decreased the frequency of emergence
      of erythromycin-resistant mutants in C. jejuni (<10(11), well below the normal
      frequency of approximately 10(8)). Together, these findings indicate that EPI MC
      207,110 inhibits the function of CmeABC efflux pump and potentiates the activity
      of antibiotics against Campylobacter. Inhibition of CmeABC by EPI is a promising
      approach in combating antibiotic resistance of Campylobacter in humans and animal
      reservoirs.

PMID- 17199522
TI  - Overview and summary of the Food Safety and Inspection Service risk assessment
      for Salmonella enteritidis in shell eggs, October 2005.
AB  - In 1998, the United States Department of Agriculture's Food Safety and Inspection
      Service (FSIS) and the Food and Drug Administration completed a risk assessment
      that indicated multiple interventions along the farm-to-table chain were needed
      to reduce the risk of human illness from Salmonella Enteritidis in shell eggs.
      Based on newly available data and improved modeling techniques, FSIS completed an
      updated risk assessment to examine the effect of pasteurization and refrigeration
      on reducing human illnesses from S. Enteritidis in shell eggs. The risk
      assessment model was written in Visual Basic for Applications (Microsoft,
      Redmond, WA) and run using Monte Carlo methods. The model estimated that if all
      shell eggs produced in the United States were pasteurized for a 3-log10 reduction
      of S. Enteritidis, the annual number of illnesses from S. Enteritidis in eggs
      would decrease from approximately 130,000 to 40,000. Pasteurization for a 5-log10
      reduction of S. Enteritidis was estimated to reduce the annual number of
      illnesses to 19,000. The model also estimated that if all eggs produced in the
      United States were stored and held at 7.2 degrees C within 12 hours of lay, the
      annual number of illnesses from S. Enteritidis in eggs would decrease from
      130,000 to 28,000. As a result, rapid cooling and pasteurization of shell eggs
      were predicted to be highly effective mitigations for reducing illnesses from
      consumption of S. Enteritidis in shell eggs.

PMID- 17199523
TI  - Seasonal shedding of Escherichia coli O157:H7 in ruminants: a new hypothesis.
AB  - Seasonal shedding of Escherichia coli O157:H7 in ruminants is well documented;
      however, viable explanations for this phenomenon are lacking. The fecal
      prevalence of E. coli O157:H7 in ruminants is the highest in the summer months,
      decreasing to low or undetectable levels in the winter. To determine if day
      length is correlated to seasonal shedding, nine reports of E. coli O157:H7
      prevalence in cattle were selected for similarity of sampling technique, culture
      methodology, cattle type, and ability to determine approximate sampling month and
      location, representing three regions in North America (southern Canada,
      midwestern United States, and the southern United States/Mexico). Correlation and
      regression analysis revealed a positive correlation existed between day length (r
      = 0.67; R2 = 0.45; P = 0.0009) and, to a lesser extent, ambient temperature (r =
      0.43; R2 = 0.19; P = 0.05) and E. coli O157:H7 prevalence. Based on these
      results, a study was conducted in a commercial feedlot to examine the effect of
      artificial lighting on E. coli O157 prevalence. Four pens of cattle received
      approximately 5 hours of artificial lighting daily (in addition to the natural
      light) for 60 days and four pens served as controls. Freshly voided fecal samples
      (representing approximately 30% of the steers/pen) were collected from the pen
      floor and cultured for E. coli O157 after 25 and 53 days of artificial lighting
      and 28 and 43 days following cessation of the lighting treatment. Fecal
      prevalence of E. coli O157 remained constant in the lighted pens whereas
      prevalence was lower (P < 0.01) in the control treatment after 53 days of
      lighting. Forty-three days following cessation of the lighting treatment,
      prevalence decreased in the lighted treatment group to levels comparable (P >
      0.20) to control levels. Understanding the mechanisms underlying the seasonality
      of this important foodborne pathogen will enable the implementation of effective
      control strategies when it is most prevalent.

PMID- 17199524
TI  - Human health impact of Salmonella contamination in imported soybean products: a
      semiquantitative risk assessment.
AB  - The objectives of our study were to estimate the number of reported cases of
      human salmonellosis in Denmark that can be attributed to the occurrence of
      Salmonella in soy-based animal feed and to assess whether certain serotypes can
      be considered of less importance to human health. The assessment was based on a
      comparison of Salmonella serotypes isolated from feedstuffs, swine, cattle, and
      humans, primarily collected through the Danish Salmonella surveillance programs,
      supplemented with international data sources. The results are presented in three
      different forms: a qualitative assessment of all serotypes isolated from animal
      feed and/or food-producing animals based on their detection in humans; a
      semiquantitative ranking of serotypes by the apparent differences in their public
      health impact; and an estimate of the number of reported cases of human
      salmonellosis that can be attributed to the occurrence of Salmonella in soy-based
      animal feed. Salmonella isolates included in this study belonged to 91 distinct
      serotypes. Of the 82 serotypes found in both production animals and humans, 45
      were also found in feed. In the period from 1999 to 2003, 14.4% of reported human
      infections were caused by serotypes also isolated from animal feed. Based on a
      modified version of a previously published risk model, we estimated that up to
      1.7% of the total number of reported human cases and 2.1% of domestically
      acquired infections in the period 1999-2003 could be attributed to feedborne
      serotypes acquired through the consumption of Danish pork and beef. We concluded
      that more than 90% of serotypes have the potential, if they occur in feedstuffs,
      for infecting humans via production animals or foods of animal origin.

PMID- 17199525
TI  - Factors associated with seeking medical care and submitting a stool sample in
      estimating the burden of foodborne illness.
AB  - Laboratory-based surveillance is a foundation for public health and is essential
      for determining the incidence of most foodborne diseases caused by bacterial
      pathogens; however, reported cases represent a subset of infections in the
      community. To identify the factors associated with seeking medical care and
      submitting a stool specimen among persons with acute diarrheal illness, we used
      multivariate logistic regression to analyze data from two 12- month population
      based telephone surveys conducted in the Foodborne Diseases Active Surveillance
      Network (FoodNet) from 2000 to 2003. Of 31,082 persons interviewed, 5% reported
      an acute diarrheal illness in the four weeks prior to the interview; of these,
      20% sought medical care. On multivariate analysis, among persons with an acute
      diarrheal illness, factors associated with seeking medical care included: male
      sex; age <5 or >or=65 years; household income <25,000 dollars; having health
      insurance; diarrhea duration >or=3 days; having bloody diarrhea, fever, vomiting,
      sore throat, or cough. Of those seeking medical care, 19% provided a stool
      sample. Bloody diarrhea (odds ratio [OR] 3.35; 95% confidence interval [CI] 1.18
      9.51) and diarrhea duration >or=3 days (OR 3.81; 95% CI: 1.50-9.69) were the most
      important factors associated with submission of a stool specimen. Cases of acute
      diarrheal illness ascertained through laboratory-based public health surveillance
      are likely to differ systematically from unreported cases and likely over
      represent those with bloody diarrhea and longer diarrhea duration.

PMID- 17199526
TI  - Thermal tolerance of acid-adapted and non-adapted Escherichia coli O157:H7 and
      Salmonella in ground beef during storage.
AB  - Thermal tolerance of acid-adapted Escherichia coli O157:H7 or Salmonella in
      ground beef was evaluated during storage at 4 degrees C or -20 degrees C. Both
      pathogens were adapted to acidic conditions (pH approximately 4.6) by growing in
      tryptic soy broth supplemented with 1% glucose. A five-strain cocktail of E. coli
      O157:H7 or Salmonella was grown separately in TSB (pH approximately 6.6) and TSB
      + 1% glucose for 24 h at 37 degrees C to provide cells with or without acid
      adaptation. Irradiated ground beef was inoculated with either acid-adapted or non
      adapted E. coli O157:H7 or Salmonella; the samples stored at 4 degrees C were
      subjected to heat treatment at 62 degrees C or 65 degrees C on days 1, 7, 14, 21,
      and 28, and the samples stored at -20 degrees C were subjected to heat treatment
      at 62 degrees C or 65 degrees C on days 1, 30, 60, 90, and 120. Decimal reduction
      time (D values) of the pathogens was determined as an indicator of thermal
      tolerance. Significantly higher D(62) values were observed on days 21 and 28 for
      non-adapted E. coli O157:H7 stored at 4 degrees C and on days 90 and 120 for non
      adapted E. coli O157:H7 stored at -20 degrees C (P < 0.05). Higher D(62) values
      were observed on days 21 and 28 among non-adapted Salmonella strains stored at 4
      degrees C and on day 28 for acid-adapted strains of Salmonella stored at 4
      degrees C (P < 0.05). Higher D(62) values for acid-adapted strains of Salmonella
      stored at -20 degrees C were observed on days 30, 60, and 90 (P < 0.05), when
      while no differences were observed in the D(65) values of acid-adapted and non
      adapted strains of E. coli O157:H7 and Salmonella throughout storage at both
      temperatures (P > 0.05). This suggests that acid adaptation of foodborne
      pathogens provides a certain level of protection against heat treatment at lower
      cooking temperatures, while at higher temperatures there were no observed
      differences between the sensitivity of acid-adapted and non-adapted strains in an
      actual food system over an extended period of refrigerated and frozen storage.

PMID- 17199527
TI  - Methodological quality assessment of review articles evaluating interventions to
      improve microbial food safety.
AB  - Review articles are a means of summarizing the potentially vast volume of
      research on a topic. However, the methodological quality of review articles
      varies, and reviews on the same topic may reach different conclusions. We
      evaluated 65 review articles published between 2000 and 2005 that addressed the
      effectiveness of microbial food safety interventions, using criteria for
      methodological soundness developed in the medical field. Overall, the
      methodological quality of the review articles was poor, with none of the reviews
      providing information on the method of locating primary research studies or the
      inclusion/exclusion criteria for selecting primary studies. None of the reviews
      included a critical appraisal of the methodological quality of the primary
      studies. Less than half of the reviews stated a focused research question,
      explored possible reasons for differences in the results of primary studies,
      discussed the generalizability of results, or proposed directions for future
      research. There is a need to improve the methodological quality of review
      articles on microbial food safety interventions if they are to be of use in
      policy and decision making.

PMID- 17199528
TI  - Modified culture protocol for isolation of Mycobacterium avium subsp.
      paratuberculosis from raw milk.
AB  - A modified culture method using C18-carboxypropylbetaine (CB-18) and microscopic
      screening was evaluated for time to and limit of detection of Mycobacterium avium
      subsp. paratuberculosis (MAP) in raw milk. Bulk-tank milk samples were spiked
      with six different concentrations (10(1) to 10(6) CFU/mL) of MAP. Samples were
      processed using two different protocols. The first protocol involved specimen
      processing with the zwitterionic detergent C18-carboxypropylbetaine (CB-18) and
      lytic enzymes followed by culture on modified Middlebrook 7H10 agar plates with
      microscopic screening. The second protocol used 0.75% hexadecylpyridinium
      chloride (HPC) for specimen processing, followed by culture on Herrold's egg yolk
      medium (HEYM). Both protocols were repeated eight independent times, and the
      detection limit and time to detection were compared. The presence of MAP in
      spiked milk samples was detected between 14 and 45 days (N [number of samples],
      46; mean, 22.7; median, 19.5) using the CB-18 and microscopic screening method,
      and between 21 and 63 days (N, 47; mean, 31; median, 28) using HEYM (P < 0.001).
      Time to detection also varied with MAP concentration (P < 0.001). Higher
      concentrations of MAP were detected earlier than lower concentrations and this
      finding was independent of the method used (P = 0.479). The two methods had
      similar detection limits but the modified culture method reduced the time to
      detect MAP in raw milk for the majority of concentrations.

PMID- 17199529
TI  - Low level nitrate or nitroethane preconditioning enhances the bactericidal effect
      of suboptimal experimental chlorate treatment against Escherichia coli and
      Salmonella Typhimurium but not Campylobacter in swine.
AB  - An experimental chlorate product that targets the respiratory nitrate reductase
      enzyme of bacteria such as Salmonella and Escherichia coli has shown promising
      results in reducing concentrations of these bacteria in the gut of food animals.
      Because expression of the target enzyme is induced by nitrate, we administered
      short-duration, low level nitrate or nitroethane preconditioning treatments to
      finishing swine to see if these would enhance the ability of an experimental
      chlorate product to kill these bacteria. Results from these studies showed that
      preconditioning the gut microflora of swine with low levels of nitrate or
      nitrocompounds enhanced (more than tenfold) the ability of the chlorate product
      to kill Salmonella and E. coli, but not Campylobacter. Further studies are needed
      before these compounds can be fed as feed additives to animals, although it is
      likely that nitrate preconditioning may be more near to market than the
      nitrocompounds, which may require more comprehensive review by regulatory
      authorities.

PMID- 17199533
TI  - A randomized, double-blind, placebo-controlled study to determine the safety and
      efficacy of cultured and expanded autologous fibroblast injections for the
      treatment of interdental papillary insufficiency associated with the papilla
      priming procedure.
AB  - BACKGROUND: The aim of this study was to assess the efficacy and safety of using
      autologous fibroblast injections following a minimally invasive papilla priming
      procedure to augment open interproximal spaces. METHODS: Twenty-one patients with
      open interproximal spaces were enrolled in this study, with 20 patients retained
      to study completion. Two primary sites were selected and randomized to receive
      autologous fibroblast injections or placebo injections beginning 1 week following
      the papilla priming procedure; two additional injections were performed 7 to 14
      days following the initial injections. Up to seven additional sites could be
      treated per patient, and the analyses were conducted for the primary and
      secondary sites. The primary efficacy parameter was the percentage change in
      papillary height of the primary treatment areas from baseline to the 4-month
      visit, as measured by a periodontal probe from the base of the contact area to
      the tip of the interproximal papilla. Digital image analysis and diagnostic
      models were used to confirm clinical measurements. A visual analog scale (VAS)
      was used by the examiner and subject to assess the defect change from baseline to
      2, 3, and 4 months. Tissue texture also was assessed by the examiner. RESULTS:
      The primary efficacy analysis failed to show a significant treatment effect at 4
      months, but the treatment areas showed a statistically significant mean
      percentage increase from baseline in papillary height (P = 0.0067; signed-rank
      test) at 2 months. The difference between test and placebo sites in papillary
      height at 2 months approached statistical significance (P = 0.0730), suggesting
      that the test treatment was superior to the placebo treatment. The examiner and
      subject VASs were statistically significantly different from baseline for both
      treatment groups, and the VAS was superior for the test sites over the placebo.
      Based on safety data, the test treatment was deemed safe. CONCLUSIONS: This early
      phase study using cell transplantation of autologous cultured and expanded
      fibroblasts following a papilla priming procedure suggests that the treatment is
      safe and may be efficacious for treating papillary insufficiency, especially in
      the early phases (2 months) of healing. The analysis of the investigator and
      subject VAS assessments indicates that the test treatment was superior to the
      placebo treatment. The finite measurement required to detect a change creates a
      problem that needs to be addressed in future studies.

PMID- 17199534
TI  - Success of dental implants placed in intraoral block bone grafts.
AB  - BACKGROUND: The purpose of this study was to evaluate the survival and success of
      dental implants placed in alveolar bone following augmentation using intraoral
      block bone grafts. METHODS: A consecutive retrospective study was conducted on
      patients who had onlay bone grafts for vertical or horizontal augmentations
      followed by dental implantation from 1999 to 2001. Files of 50 healthy patients
      who received 129 implants in augmented sites were reviewed. Implant survival,
      radiologic implant success (marginal bone loss), and complications were recorded.
      RESULTS: Follow-up from time of implantation ranged from 6 to 67 months (mean:
      24.3 +/- 11.2 months). Ranges of implant widths and lengths were 3.25 to 4.7 mm
      and 10 to 16 mm, respectively. The overall survival rate was 96.9% (four implants
      were removed). Marginal bone loss around implants ranged from 0 to 3.3 mm
      (average: 0.22 +/- 0.45 mm). Only 5% of the implants presented marginal bone loss
      > or =1.5 mm over the follow-up time. CONCLUSIONS: Intraoral bone block graft
      surgery is a predictable operation for the use of dental implants. Implant
      placement in augmented areas presents high survival and radiologic success rates
      with minimal bone loss.

PMID- 17199535
TI  - The effectiveness of subgingival scaling and root planing: an evaluation of
      therapy with and without the use of the periodontal endoscope.
AB  - BACKGROUND: A fiber-optic periodontal endoscope was developed to aid in the
      visualization of subgingival structures and to improve the diagnosis and
      management of periodontal diseases. The purpose of this study was to determine
      whether use of the periodontal endoscope with scaling and root planing (SRP)
      resulted in a decrease in residual calculus compared to SRP alone. METHODS:
      Fifteen subjects with 50 tooth pairs participated in this study. Each tooth per
      pair was randomized to receive SRP with or without the endoscope. Teeth were
      extracted, and a stereomicroscope and digital image analysis was used to
      determine percent residual calculus present in a masked fashion. RESULTS: There
      was 2.14% (P < 0.001) more residual calculus at control versus test sites. At
      buccal/lingual and interproximal surfaces, mean differences in residual calculus
      were 1.30% (P <0.015) and 2.93% (P < 0.001), respectively. Test treatment time
      decreased significantly as operator experience increased. There were no
      statistically significant differences between residual calculus for test and
      control teeth at shallower probing depths; however, at deeper probing depths, the
      use of the endoscope resulted in significantly less residual calculus.
      CONCLUSIONS: The use of the periodontal endoscope resulted in a statistically
      significant overall improvement in calculus removal during SRP, which was most
      evident in deeper probing depths. The clinical significance of this level of
      improvement is unknown.

PMID- 17199536
TI  - Cross-sectional evaluation of the presence of gingival recession in individuals
      with cleft lip and palate.
AB  - BACKGROUND: In dentistry, investigations in the field of periodontics in
      individuals with cleft lip and palate are scarce, with few studies on the
      prevalence, incidence, extension, and severity of periodontal alterations and
      their treatment in adults. METHODS: This study analyzed the prevalence,
      extension, and severity of recessions and the relationship with some etiologic
      factors in 200 individuals with cleft lip and palate aged 13 to 56 years.
      Examination comprised measurements of gingival recession, amount of keratinized
      mucosa, frenum insertions, and tooth positioning in the dental arch. RESULTS:
      Analysis of the results revealed that the prevalence of recession was high,
      because 75% of individuals in the sample had at least one tooth with gingival
      recession; 100% of individuals aged >43 years presented at least one recession,
      and most recessions were Miller Class I. The multiple linear regression
      demonstrated that recession is directly proportional to age (i.e., it increases
      with age); concerning the amount of keratinized mucosa, the proportion is inverse
      (i.e., the larger the recession, the smaller the amount of mucosa); and gingival
      inflammation also presented a positive correlation. CONCLUSIONS: Gingival
      recessions are caused by many etiologic factors, which usually act in
      combination. Thus, all factors causing recession should be analyzed so that
      planning and treatment of this clinical condition may be established, for
      achievement of optimal outcomes.

PMID- 17199537
TI  - Stability of clinical and radiographic results after guided tissue regeneration
      in infrabony defects.
AB  - BACKGROUND: The aim of this 5-year follow-up study was to evaluate clinically and
      radiographically the long-term results after guided tissue regeneration (GTR)
      therapy of infrabony defects using non-resorbable and bioabsorbable barriers.
      METHODS: Thirty-one patients with periodontitis and 50 infrabony defects that had
      been treated using GTR were recruited. Eleven defects were treated with non
      resorbable expanded polytetrafluoroethylene membranes and 39 defects with
      bioabsorbable barriers. At baseline and 6 and 60 +/- 3 months after surgery,
      clinical parameters and standardized radiographs were obtained. During surgery
      and 60 +/- 3 months thereafter, the distance from the cemento-enamel junction to
      the base of the bony defect (vertical probing bone level [PBL-V]) was measured.
      Bone gain was evaluated using digital subtraction radiography. RESULTS: At 6 and
      60 +/- 3 months after GTR, there was a statistically significant (P <0.001)
      reduction of probing depth (6 months: 4.31 +/- 1.76 mm; 60 months: 3.95 +/- 1.62
      mm) and vertical clinical attachment level gains (CAL-V) (6 months: 3.34 +/- 1.66
      mm; 60 months: 2.97 +/- 1.53 mm). From 6 to 60 months after GTR, three infrabony
      defects exhibited CAL-V loss >2 mm, and a small, statistically not significant
      mean CAL-V loss of 0.39 +/- 1.60 mm was observed. From baseline to 60 +/- 3
      months, a significant PBL-V gain of 1.78 +/- 2.67 mm (P <0.001) and increase in
      bone density were observed (P = 0.003). CONCLUSION: The CAL-V gain achieved after
      GTR in infrabony defects using both non-resorbable and bioabsorbable barriers was
      stable after 5 years in 47 of 50 defects.

PMID- 17199539
TI  - Wide-diameter implants: analysis of clinical outcome of 304 fixtures.
AB  - BACKGROUND: In the last decade, the use of wide-diameter implants (WDIs; diameter
      >3.75 mm) has increased. Although good clinical outcomes have been reported in
      recent literature, there are few reports on this topic. Thus, we planned a
      retrospective study on a large series of WDIs to evaluate the clinical outcome.
      METHODS: From October of 1996 to December of 2004, 205 patients were operated on,
      and 304 WDIs were inserted. The mean postloading follow-up was 30 months. Implant
      diameter and length ranged from 5.0 to 6.5 mm and from 8.0 to 15 mm,
      respectively. Because only five of 304 implants were lost (i.e., a survival rate
      of 98.4%) and no statistical differences were detected among the studied
      variables, no or reduced crestal bone resorption (CBR) was considered an
      indicator of success to evaluate the effect of several host-, surgery-, and
      implant-related factors. A general linear model (GLM) was performed to detect
      variables that were associated statistically with CBR. RESULTS: Only five of 304
      WDIs were lost, and no differences were detected among the studied variables. On
      the contrary, the GLM showed that distal teeth (i.e., premolars and molars),
      small implant diameter (i.e., 5.0 and 5.5 mm), and short implant length (i.e.,
      <13 mm) correlated with a statistically significant lower CBR. CONCLUSION: The
      use of WDIs is a viable treatment option, and it may provide benefits in
      posterior regions for long-term maintenance of various implant-supported
      prosthetic rehabilitations.

PMID- 17199538
TI  - Clinical significance of incision location on guided bone regeneration: human
      study.
AB  - BACKGROUND: Membrane exposure has been associated with poor clinical outcomes in
      guided bone regeneration. This prospective human study examined the effect of
      incision locations on flap survival and membrane exposure. METHODS: Twenty-nine
      implant-associated buccal dehiscence defects in 25 patients were augmented using
      particulate mineralized human allograft. Ten sites received a collagen
      bioabsorbable membrane, 10 sites received acellular dermal matrix, and nine sites
      were treated with bone graft alone. All implants achieved primary stability and
      passive flap tension at the time of flap closure. Incision location was measured
      as the distance from the initial incision line to the mucogingival junction. The
      same measurements were made at 2 weeks and 1 month to represent the length of the
      flap that survived. The length of the flap that survived at 2 weeks was compared
      to the mean width of buccal keratinized gingiva (KG) of adjacent teeth. Other
      clinical parameters recorded included incidence of early membrane exposure and
      gingival thickness at mid-crest and 6 mm buccal and lingual to the mid-crest at
      baseline. RESULTS: At 2 weeks, 10 sites experienced early exposure. Exposed sites
      that were not covered by 1 month remained exposed. Membrane-treated groups showed
      no significant difference between the width of adjacent buccal KG and the length
      of the flap that survived at 2 weeks. The length of the flap that survived beyond
      the mean width of adjacent KG was significantly greater for the graft alone group
      (1.6 +/- 0.4 mm; P = 0.002). When the gingival thicknesses of exposed and non
      exposed cases were compared, only palatal/lingual gingival thickness showed a
      significant difference (P = 0.002). CONCLUSIONS: Within the limits of the study,
      it was concluded that the location of the crestal incision might be a significant
      factor in reducing the incidence of membrane exposure by minimizing flap
      necrosis. The mean KG width of adjacent teeth may be used as a guide to determine
      the initial incision location. However, this effect may be less significant in
      palatal/lingual gingiva >3.0 mm.

PMID- 17199540
TI  - Periodontal disease in Kuna albinism: a comparative study.
AB  - BACKGROUND: In classic albinism, all parts of the body are normal except for the
      absence of melanin. It is believed that lack of this pigment in periodontal
      tissues might influence periodontal disease progression. This study was designed
      to determine the relationship between periodontal diseases and albinism by
      comparing the clinical periodontal status of a group of native Panamanian Kuna
      albinos (from San Blas, Panama) to Kuna non-albinos of the same communities.
      METHODS: An experimental group of 30 subjects (Kuna albinos aged > or =12 years)
      was selected and divided into three subgroups according to age. Likewise, a
      control group of 30 subjects (Kuna non-albinos) was selected and divided in
      subgroups. RESULTS: Assessment of oral hygiene and gingival inflammation in
      albinos by the Silness and Loe plaque index and Loe and Silness gingival index,
      respectively, was unremarkable compared to control groups. No statistically
      significant differences were found for number of teeth present, gingival index,
      plaque index, clinical attachment loss (CAL), probing depth, or gingival
      recession. As expected, age was a factor in the severity of the periodontal
      disease; 58% of individuals aged > or =36 years had at least one site with CAL >
      or =7 mm. CONCLUSION: Based on the overwhelming similarity of results found
      between experimental and control groups, albinism does not represent a clinical
      risk factor in the pathogenesis or exacerbation of periodontal diseases for these
      individuals.

PMID- 17199541
TI  - Anxiety, stress, depression, and patients' responses to periodontal treatment:
      periodontists' knowledge and professional behavior.
AB  - BACKGROUND: Anxiety, stress, and depression affect the use of health care
      services, treatment decision-making, and responses to periodontal treatment. This
      study explored periodontists' confidence in detecting patient anxiety, stress, or
      depression, as well as their knowledge concerning the relationships between these
      factors and patients' pain, use of pain medication, and wound healing after
      periodontal treatment. In addition, this research surveyed if (and which) special
      accommodations were offered when treating patients with high levels of anxiety,
      stress, or depression. METHODS: Data were collected from 171 members of the
      American Academy of Periodontology (response rate = 34.41%). Most respondents
      were male (82.2%), white (88.2%), and practiced in solo practices (60.9%).
      RESULTS: The respondents were more knowledgeable about the effects of anxiety and
      stress on pain, the use of pain medication, and wound healing than about the
      impact of depression on these outcomes. They agreed more strongly with statements
      that they were more confident in their ability to perceive when patients were
      anxious and stressed than when they were depressed. They also offered more
      special accommodations for patients with anxiety and stress than for patients
      with depression. CONCLUSIONS: The respondents were significantly less
      knowledgeable about the impact of depression on patients' responses to
      periodontal treatment than about the effect of anxiety and stress. Given the
      evidence concerning the relationships among depression, pain, pain medication
      use, and wound healing, it is important to educate periodontists about the role
      of anxiety and stress and the significance of depression on their patients'
      responses to periodontal therapy.

PMID- 17199542
TI  - Two subgingival plaque-sampling strategies used with RNA probes.
AB  - BACKGROUND: The purpose of this study was to compare the results of
      microbiological RNA-probe analysis after subgingival plaque sampling applying two
      different strategies. METHODS: In 220 patients, clinical examinations were
      obtained prior to commencement of therapy for aggressive or generalized severe
      chronic periodontitis (n = 113), after combined mechanical and antibiotic anti
      infective periodontal therapy (n = 43), or because of periodontal pockets despite
      adequate therapy (n = 64). Subgingival plaque samples were obtained from the
      three pockets with the deepest probing depths. Two sterile paper points were
      inserted simultaneously into the periodontal pockets. One paper point from each
      pocket was put into a separate transport vial; the second paper point was pooled
      (multiple site test [MT3]) with paper points from each of the two other sampling
      sites from the respective patient into a transport vial. The content of each vial
      was analyzed separately for Actinobacillus actinomycetemcomitans, Tannerella
      forsythensis, Porphyromonas gingivalis, and Treponema denticola (Td) with a
      commercially available RNA-probe test. RESULTS: For all tested pathogens, log
      transformed numbers of bacteria were higher in pooled samples compared to the
      mean values for the separate samples (P < or =0.01). However, for Td only,
      statistically significant differences in frequency were seen between the separate
      samples and MT3. These findings were observed over all samples as well as after
      evaluation of subgroups separately. CONCLUSIONS: Pooling of plaque samples
      increased the bacterial counts per analysis compared to separate samples and thus
      may increase the probability of detecting existing pathogens. However, this
      observation only was statistically significant for the frequency of Td.

PMID- 17199543
TI  - Comparison of subgingival bacterial sampling with oral lavage for detection and
      quantification of periodontal pathogens by real-time polymerase chain reaction.
AB  - BACKGROUND: Saliva has been studied for the presence of subgingival pathogens in
      periodontitis patients. With the anaerobic culture technique, the discrepancy
      between salivary recovery and subgingival presence has been significant, which
      makes this approach not suitable for practical use in the microbial diagnosis of
      periodontitis patients. The real-time polymerase chain reaction (PCR) technique
      represents a very sensitive technique to detect and quantify bacterial pathogens.
      The aim of the study was to compare the presence and numbers of Actinobacillus
      actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensis,
      Prevotella intermedia, and Micromonas micros in subgingival plaque and mouthwash
      samples by the anaerobic culture and real-time PCR techniques. METHODS: Pooled
      subgingival plaque samples and 10-ml mouthwash samples were collected from 21
      adult patients with periodontitis and analyzed by quantitative anaerobic culture
      and real-time PCR for A. actinomycetemcomitans, P. gingivalis, T. forsythensis,
      P. intermedia, and M. micros. RESULTS: The detection frequency of A.
      actinomycetemcomitans, P. gingivalis, and T. forsythensis in subgingival plaque
      was identical by culture and real-time PCR and was higher for P. intermedia and
      M. micros by real-time PCR. The highest detection frequencies for the target
      bacteria were found in mouthwash samples by real-time PCR. The additional value
      of the real-time PCR to detect target bacteria was 38% for P. gingivalis, 73% for
      T. forsythensis, 77% for P. intermedia, and 71% for M. micros. The sensitivity to
      detect target species in mouthwash by real-time PCR was 100% for all test species
      except for P. intermedia (93.8%). CONCLUSIONS: Rapid detection and quantification
      of periodontal pathogens in mouthwash samples are possible by real-time PCR. The
      procedure is significantly less time-consuming than subgingival sampling with
      paper points. This approach to detect major periodontal pathogens in mouthwash
      samples may simplify microbial diagnosis in periodontitis patients and may be
      used to monitor periodontal treatment.

PMID- 17199545
TI  - Pinch forces and instrument tip forces during periodontal scaling.
AB  - BACKGROUND: The prevalence of upper-extremity musculoskeletal disorders, such as
      tendinitis, is elevated among dental practitioners. An important risk factor for
      these disorders is forceful pinching; however, the pinch forces and instrument
      forces during scaling are unknown. METHODS: Six dentists and six senior-year
      dental students were recruited to use an instrumented periodontal scaler to
      perform their usual dental scaling work on patients. Thumb pinch force was
      measured by a pressure sensor, whereas the forces developed at the instrument tip
      were measured by a six-axis load cell. RESULTS: Dental students applied greater
      mean peak pinch force (35.7 +/- 3.8 N) compared to dentists (24.5 +/- 4.1 N) (P =
      0.001). On the other hand, the peak forces generated at the instrument tip, which
      were directly related to the productivity of the dental scaling task, were higher
      among the dentists. The application of pinch force by dentists was related to the
      required scaling forces, whereas students applied excessive pinch force to the
      tools. CONCLUSIONS: Increased experience in periodontal scaling leads to the
      application of less pinch force to accomplish scaling. Nonetheless, the applied
      peak pinch forces in both groups are high and may pose a risk for the development
      of musculoskeletal disorders of the distal upper extremity.

PMID- 17199544
TI  - Clinical and microbiological profiles of human immunodeficiency virus (HIV)
      seropositive Brazilians undergoing highly active antiretroviral therapy and HIV
      seronegative Brazilians with chronic periodontitis.
AB  - BACKGROUND: This study compares the periodontal clinical profile and the
      composition of the subgingival microbiota of human immunodeficiency virus (HIV)
      seropositive and HIV-seronegative subjects with chronic periodontitis. METHODS: A
      total of 172 subjects were distributed into two HIV-seropositive groups (37
      chronic periodontitis [H+CP+] and 35 periodontally healthy [H+CP-] individuals)
      and two HIV-seronegative groups (49 chronic periodontitis [H-CP+] and 51
      periodontally healthy [H-CP-] subjects). Subgingival samples were collected from
      six sites with the deepest probing depth in the periodontitis groups and six
      random sites in the groups with periodontal health. All HIV-infected patients had
      undergone highly active antiretroviral therapy (HAART) for at least 2 years. The
      presence and levels of 33 bacterial species were detected by DNA probes and the
      checkerboard method. Kruskal-Wallis and Mann-Whitney tests were used to seek for
      significant differences among and between groups. RESULTS: H-CP+ patients showed
      significantly more periodontal destruction and inflammation than H+CP+ patients,
      whereas H+CP- subjects presented a greater percentage of sites with bleeding than
      H-CP- subjects (P <0.01). Patients who were HIV seronegative showed higher
      prevalence and levels of most bacterial species than HIV seropositive patients.
      Periodontal pathogens including Tannerella forsythensis, Porphyromonas
      gingivalis, Prevotella nigrescens, Eubacterium nodatum, Fusobacterium nucleatum,
      and Selenomonas noxia were more frequently detected in H-CP+ subjects compared to
      H+CP+ and controls. In contrast, Enterococcus faecalis and Acinetobacter
      baumannii were more commonly found in HIV-infected than in non-HIV-infected
      subjects (P <0.05). CONCLUSION: Putative periodontal pathogens are more prevalent
      in the subgingival microbiota of HIV-seronegative patients with chronic
      periodontitis, whereas species not usually associated with periodontitis are
      detected in higher frequency in HIV-seropositive subjects under HAART.

PMID- 17199546
TI  - Gingival crevicular fluid prostaglandin E(2) and thiobarbituric acid reactive
      substance levels in smokers and non-smokers with chronic periodontitis following
      phase I periodontal therapy and adjunctive use of flurbiprofen.
AB  - BACKGROUND: It has been established that smoking is an important risk factor for
      the initiation and progression of chronic periodontitis (CP). This study
      investigates the effects of phase I periodontal therapy and adjunctive
      flurbiprofen administration on prostaglandin E(2) (PGE(2)) and thiobarbituric
      acid reactive substance (TBARS) levels in gingival crevicular fluid (GCF) samples
      from smoker and non-smoker patients with CP. METHODS: Twenty-one non-smoker and
      21 smoker patients with CP were divided into four groups according to treatment
      modalities. Group 1 (non-smokers with CP) and group 3 (smokers with CP) patients
      received daily 100-mg flurbiprofen tablets in a 2 x 1 regimen for 10 days
      together with scaling and root planing (SRP). Patients in group 2 (non-smokers
      with CP) and group 4 (smokers with CP) received placebo tablets in a 2 x 1
      regimen for 10 days together with SRP. Plaque index (PI), gingival index (GI),
      probing depth (PD), and clinical attachment level (CAL) measurements were
      recorded and GCF samples were collected at baseline and on day 10 of drug intake
      from each sampling area by a single examiner who was unaware of the treatment
      modality. Assays for GCF PGE(2) and TBARS were carried out by an enzyme-linked
      immunosorbent assay and fluorometric method, respectively. RESULTS: All groups
      showed statistically significant reductions in PI and GI scores following the
      phase I periodontal treatment on day 10 (P <0.05), but no statistical differences
      were observed in PD and CAL scores after the therapy. In groups 1 and 2, the
      reduction of GCF PGE(2) and TBARS levels were not significant after the therapy
      compared to baseline levels. In group 3, GCF PGE(2) and TBARS levels exhibited a
      statistically significant decrease (P <0.05) after the therapy. Group 4 showed
      significant reductions (P <0.05) in GCF PGE(2) levels after the therapy. No
      statistically significant reductions were observed in group 4 with regard to GCF
      TBARS levels. When groups 1 and 3 were compared according to GCF TBARS levels
      after the therapy, a more statistically significant reduction was observed in
      group 3 (P = 0.001). CONCLUSION: These results suggest that additional
      flurbiprofen administration may have more inhibitory effects on GCF levels of
      PGE(2) and TBARS in the groups of smokers compared to non-smokers with CP.

PMID- 17199547
TI  - Ossification of a novel cross-linked porcine collagen barrier in guided bone
      regeneration in dogs.
AB  - BACKGROUND: Collagen membranes for guided bone regeneration (GBR) and guided
      tissue regeneration (GTR) are used extensively as bioabsorbable barriers. Cross
      linking of collagen increases its biodurability and enables the control of its
      degradation kinetics and barrier function. A novel cross-linking technology was
      used to produce a porcine type I collagen membrane (GLYM). The purpose of this
      study was to evaluate the safety, efficacy, and degradation kinetics of GLYM
      compared to a non-cross-linked bilayer type I and III porcine collagen membrane
      (BCM) in surgically created defects in dogs. METHODS: After tooth extraction, two
      mandibular bilateral critical size defects were created in 12 beagle dogs that
      were randomly assigned to one of five groups: GLYM + bovine bone mineral (BBM),
      BCM + BBM, BBM alone, sham-operated, or GLYM alone. Dogs were euthanized after 8,
      16, and 24 weeks, and sites were prepared for qualitative, semiquantitative, and
      quantitative light microscopy analyses. RESULTS: Membrane-protected sites
      displayed bone filling between the BBM particles with almost complete restoration
      of the original ridge morphology that increased with time up to 16 weeks and
      remained unchanged at 24 weeks. Both membranes showed marked degradation within
      16 to 24 weeks, with BCM inconsistency that was undetectable in one of four sites
      at 8, 16, and 24 weeks. Membrane ossification was observed in all GLYM sites and
      in only one BCM site, which progressed with time to 24 weeks. Bone increased by
      approximately 1 mm on the lingual side, where the GLYM membrane was in direct
      contact with bone. CONCLUSIONS: Both membranes were safe and effective in
      supporting bone regeneration in critical size alveolar ridge defects in dogs and
      completely degraded within 24 weeks with marked BCM inconsistency. In areas of
      direct contact with bone, all GLYM sites were progressively ossified with time
      and augmented the original alveolar ridge. To the best of our knowledge, this is
      the first report of complete ossification of a collagen barrier membrane in GBR
      procedures.

PMID- 17199548
TI  - Calculus removal with diamond-coated ultrasonic inserts in vitro.
AB  - BACKGROUND: Efficient calculus removal is a primary goal in periodontal therapy.
      Diamond-coated ultrasonic inserts (DIs) offer promise for improved scaling and
      were evaluated in vitro. METHODS: Extracted human teeth with moderate to severe
      calculus had areas of calculus ( approximately 5 x 5 mm) delineated with small
      burs. Each calculus area was treated under 2.5x magnification to the point of
      visible root cleanliness with sharp Gracey curets (hand instruments [HIs]), plain
      ultrasonic inserts (PIs), or ultrasonic inserts with fine-grit diamond coating;
      the latter two were used in a magnetostrictive ultrasonic instrument at a medium
      power setting. Each curet or insert was used for four teeth and then replaced by
      a new instrument. The time needed to clean each tooth/surface was recorded. The
      total area treated and the area of the residual calculus were calculated using an
      imaging analysis program. RESULTS: The mean time required for clinical calculus
      removal was 29.7 seconds for DIs, 91.9 seconds for PIs, and 49.8 seconds for HIs
      (all P <0.0001 from each other). Overall, the mean percentage of residual
      calculus was 6.3% for DIs, 5.4% for PIs, and 3.1% for HIs (significant
      differences between HIs and the other treatments). CONCLUSIONS: In vitro calculus
      removal was faster with DIs, followed by HIs and PIs. More residual calculus was
      found with the DIs; however, the 1% to 3% difference (93.7% clean versus 94.6%
      clean versus 96.9% clean with DIs, PIs, and HIs, respectively) does not seem to
      be clinically significant.

PMID- 17199550
TI  - Cyclooxygenase-2-dependent prostaglandin E(2) upregulates interleukin (IL)-1alpha
      induced IL-6 generation in mouse cementoblasts.
AB  - BACKGROUND: Prostaglandin E(2) (PGE(2)), which exerts its biologic actions via EP
      receptors (EP(1), EP(2), EP(3,) and EP(4)), is a bioactive metabolite of
      arachidonic acid that is produced by cyclooxygenase (COX)-1 and/or COX-2. In the
      present study, we investigated whether a mouse cementoblast cell line, OCCM-30
      cells, that was stimulated with interleukin (IL)-1alpha produced COX-2-dependent
      PGE(2) and whether the produced PGE(2) affected IL-1alpha-induced IL-6
      production. METHODS: OCCM-30 cells were stimulated with vehicle or IL-1alpha in
      the presence or absence of indomethacin (a COX-1/COX-2 inhibitor), NS-398 (a
      specific COX-2 inhibitor), PGE(2), and EP receptor agonists. PGE(2) and IL-6
      levels were assayed by enzyme linked immunosorbent assay. RESULTS: IL-1alpha
      induced PGE(2) production in a time-dependent fashion. Indomethacin and NS-398
      completely inhibited IL-1alpha-induced PGE(2) production. 17-phenyl-omega-trinor
      PGE(2) (an EP(1) agonist) and an EP(4) agonist mimicked PGE(2) enhancement of IL
      1alpha-induced IL-6 production in OCCM-30 cells. CONCLUSIONS: From these data, we
      suggest that IL-1alpha induced PGE(2) production in a COX-2-dependent manner in
      OCCM-30 cells and that the COX-2-derived PGE(2) upregulates IL-1alpha-elicited IL
      6 production via EP(1) and/or EP(4) receptors. PGE(2) and IL-6 produced by
      cementoblasts may be involved in the pathogenesis of periodontal disease.

PMID- 17199551
TI  - In vitro effects of enamel matrix derivative on microvascular cells.
AB  - BACKGROUND: Periodontal regeneration requires a coordinated series of events that
      includes not only the recruitment of periodontal ligament (PDL)-specific cells,
      but vascular cells as well. The mechanisms of action of enamel matrix derivative
      (EMD) are poorly understood, and its effects on vascular cells are unknown. The
      objective of this study was to examine the extent to which EMD affects
      angiogenesis and PDL cell recruitment. METHODS: The effects of EMD on human
      microvascular endothelial cells (HMVECs) were determined by examining
      proliferation, chemotaxis, angiogenesis, and migration. Proliferation was
      determined using water-soluble tetrazolium salt (WST)-1 reagent. Chemotaxis was
      determined using microporous-culture well inserts. Angiogenesis was assessed on
      plates containing matrigel. The effects of HMVECs on the migration of PDL cells
      were assessed by evaluating PDL cell outgrowth from collagen gels cultured in the
      presence of HMVECs on fibrin matrix and surrounded by fibronectin-containing
      fibrin clots at 24 hours. Effects of EMD on PDL expression of vascular
      endothelial cell (VEGF) types (A, B, C, and D) and isoforms were determined using
      reverse transcription-polymerase chain reaction (RT-PCR). Production of VEGF,
      platelet-derived growth factor (PDGF)-AA, PDGF-BB, PDGF-AB, and transforming
      growth factor (TGF)-beta1 by EMD-stimulated PDL cells was assessed quantitatively
      in conditioned media using specific enzyme-linked immunosorbent assays (ELISAs).
      RESULTS: EMD at concentrations <50 microg/ml resulted in significant (P <0.05)
      stimulation of HMVEC proliferation. Compared to baseline, EMD also stimulated a
      100% increase in HMVEC chemotaxis when PDL cells were present (P <0.05). All
      doses of EMD tested (25, 50, and 100 microg/ml) increased angiogenesis in vitro.
      HMVECs, in combination with EMD at a concentration of 100 microg/ml, stimulated a
      750% increase in migration of PDL cells from collagen gels into fibrin clots
      compared to controls when neither was present. RT-PCR results indicated that PDL
      cells expressed VEGF-A, -B, and -C and multiple isoforms of VEGF-A, including
      VEGF(121), VEGF(165), and VEGF(189), whether or not EMD was present in the
      culture media. ELISAs determined a 400% increase in VEGF concentration by PDL C
      cells in EMD-stimulated conditioned media and a similar increase in TGF-beta(1)
      stimulated media. CONCLUSIONS: It is likely that EMD stimulates angiogenesis
      directly by stimulating endothelial cells and indirectly by stimulating the
      production of angiogenic factors (VEGF) by PDL cells. Importantly, the data are
      consistent with the concept that EMD enhances bidirectional communication between
      HMVEC and PDL cells during angiogenesis associated with healing.

PMID- 17199549
TI  - Matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase-1, and
      laminin-5 gamma2 chain immunolocalization in gingival tissue of endotoxin-induced
      periodontitis in rats: effects of low-dose doxycycline and alendronate.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) play important roles in tissue
      destruction mechanisms of periodontitis. MMP-8 and -13 are the major collagenases
      that act in extracellular matrix degradation in periodontal tissues. MMP-14 is a
      membrane-type MMP, and laminin (Ln)-5 is a basal membrane component. The aim of
      the present study was to evaluate the effects of doxycycline and alendronate on
      gingival tissue expression of MMP-8, -13, and -14; tissue inhibitors of MMP
      (TIMP)-1; and Ln-5 gamma2 chain in experimental periodontitis induced by
      Escherichia coli endotoxin (LPS) in rats. METHODS: Experimental periodontitis was
      induced by repeated injection of LPS. Forty-four adult male Sprague-Dawley rats
      were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS
      + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate
      were given as a single agent or as combination therapy during the 7 days of the
      experimental study period. On day 7, the rats were sacrificed, and the gingival
      tissues were analyzed immunohistochemically for expression of MMP-8, -13, and 
      14, Ln-5 gamma2 chain, and TIMP-1. Alveolar bone loss was evaluated
      morphometrically under a stereomicroscope. Data were tested statistically by
      Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. RESULTS:
      Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate,
      and combination groups than in the saline control group (all P <0.01). MMP-8
      expression was significantly higher in the LPS group than in the saline control
      group (P = 0.001). Individual administration of doxycycline or alendronate
      significantly decreased the expression of MMP-8 compared to LPS (P = 0.01).
      Combined drug administration reduced MMP-14 significantly compared to doxycycline
      (P = 0.004). No significant differences in Ln-5 gamma2 chain expression were
      found between the study groups (P >0.05). MMP-14 significantly correlated with
      the Ln-5 gamma2 chain in the LPS + alendronate group (P = 0.04) and with the
      amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P =
      0.03). CONCLUSIONS: Our findings suggest that alendronate and/or doxycycline may
      inhibit MMP-8 expression significantly; particularly, their combined
      administration may provide beneficial effects in periodontal treatment. Moreover,
      individual administration of alendronate and doxycycline results in significant
      increases in TIMP-1 expression in gingiva. However, these effects of combined low
      dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical
      human trials before these agents are used in dental practice.

PMID- 17199552
TI  - Effects of lactation on alveolar bone loss in experimental periodontitis.
AB  - BACKGROUND: The development and progression of periodontitis are accelerated by
      various systemic conditions. The present study was designed to determine whether
      lactation affects alveolar bone loss in rat models of experimental periodontitis.
      METHODS: Sixty-two female Wistar rats were bred with male rats and divided into
      three groups that were fed diets containing 0.9%, 0.3%, and 0.02% calcium. They
      were divided further into two subgroups of lactating and non-lactating animals.
      An elastic ring was placed around the neck of the right mandibular first molar to
      induce periodontitis (experimental side) on day 32 after mating. The left first
      molar was not fitted with an elastic ring (control side). After the lactation
      period, bone mineral density (BMD) was determined, and a histologic examination
      of the interdental alveolar bone was performed. RESULTS: On the experimental and
      control sides, BMD decreased significantly according to the amount of calcium in
      the diet; however, the magnitude of this decrease was much greater in the
      lactating group. Histologic examination revealed that in lactating and non
      lactating rats, the decrease in BMD was accompanied by a decrease in alveolar
      bone height on the experimental side, whereas similar results were not seen on
      the control side. CONCLUSIONS: Lactation could be a risk factor for alveolar bone
      loss, especially under conditions of calcium insufficiency. Increased systemic
      demand for calcium and an insufficient supply of calcium might enhance the
      development of alveolar bone loss in periodontitis.

PMID- 17199554
TI  - Influence of the period after ovariectomy on femoral and mandibular bone density
      and on induced periodontal disease.
AB  - BACKGROUND: This study investigated the influence of the period after ovariectomy
      on femoral and mandibular bone mineral density (BMD) and on induced periodontal
      disease. METHODS: One hundred and twenty-six female Holtzman rats were divided
      into nine groups: control, sham surgery (SHAM) with and without induction of
      periodontal disease for 51 and 150 days, and ovariectomy (OVX) with and without
      induction of periodontal disease for 51 and 150 days. Periodontal disease was
      induced by placing ligatures on the first lower molars during the last 30 days of
      each period. BMD was measured by dual-energy x-ray absorptiometry. Vertical bone
      loss was determined by measuring the distance from the alveolar bone crest to the
      cemento-enamel junction on the mesial side of the first lower molar. RESULTS:
      Statistical analyses (Kruskal-Wallis test) revealed a significant difference
      between the OVX and SHAM groups' global and femoral proximal epiphysis BMD (P
      <0.001) for 150 days and in the global evaluation for 51 days. For mandibular
      BMD, no difference was found between the groups of each period. Influence of the
      period on femoral BMD was found only for the SHAM groups, with lower BMD for the
      51-day period compared to the 150-day period (P <0.05). In the global evaluation
      of the mandible, a lower BMD was found after 51 days. The period was a
      contributing factor for the vertical bone loss, and it resulted in higher values
      for the 51-day period (P <0.05). CONCLUSION: The period influenced the femoral
      BMD and the vertical bone loss in induced periodontal disease.

PMID- 17199553
TI  - Osteopromotion with synthetic oligopeptide-coated bovine bone mineral in vivo.
AB  - BACKGROUND: Recombinant human bone morphogenetic protein (rhBMP)-2 has been shown
      to stimulate significant regeneration of alveolar bone and cementum in
      periodontal defects clinically. The aim of this study was to evaluate the
      osteopromotive effect of oligopeptide domain-coated bovine bone mineral granules
      in a rabbit calvarial defect model. METHODS: The peptide-coated bovine bone was
      fabricated by incubating the graft material in a solution of oligopeptide domain.
      The cell attachment and proliferation were measured in vitro. Peptide-coated
      (test group) or uncoated (control group) bone minerals were implanted into 10-mm
      calvarial defects in rabbits, and the animals were sacrificed at 1, 2, or 4 weeks
      post-surgery. RESULTS: The cells grown with peptide-coated bone showed
      significantly higher proliferation activity at all times compared to cells grown
      with peptide-uncoated bone mineral. At 2 weeks post-surgery, the control wounds
      showed a limited amount of osteoid formation in a centripetal pattern around the
      grafted bone, but the oligopeptide domain-coated grafted bone had formed new bone
      around the grafted area. At 4 weeks post-surgery, the control sites showed
      increased new bone formation, but they still showed a significant difference from
      the peptide-coated bone-implanted sites. CONCLUSIONS: At 2 and 4 weeks,
      accelerated new bone formation was observed within the experimental sites
      compared to control groups. The use of deproteinized bovine bone combined with a
      synthetic oligopeptide seems to be a more beneficial material for bone
      regeneration in the early healing period.

PMID- 17199555
TI  - Diffuse pigmentation of maxillary attached gingiva: four cases of the cultural
      practice of gingival tattoo.
AB  - BACKGROUND: Gingival pigmentation is a common finding, may be of endogenous or
      exogenous origin, and can have diagnostic significance. Diffuse gingival
      pigmentation may be physiologic in nature or can be due to environmental factors,
      drugs, endocrine disorders, or genetic conditions. We present four cases of
      diffuse gingival pigmentation due to traditional gingival tattooing and review
      the literature on this practice. METHODS: Four black females (aged 19 to 56
      years) of West African origin (Mauritania and Senegal), representing three
      different ethnic groups (Fulani, Mandinka, and Soninke) presented with various
      chief complaints. All exhibited diffuse pigmentation of the maxillary vestibular
      gingiva extending to the second premolar areas, without any associated
      radiographic abnormalities. The color ranged from intense blue gray to light gray
      or grayish pink. One case was biopsied for histopathologic evaluation. RESULTS:
      Questioning revealed that the women had had one or more sessions of traditional
      gingival tattooing. In one case, the procedure was performed in a dental office.
      The color range appeared to depend on the time that elapsed since the last
      procedure. The biopsy exhibited dense fibrous connective tissue containing
      aggregates of foreign material consistent with a foreign body tattoo.
      CONCLUSIONS: Gingival tattooing, a cultural practice prevalent in certain African
      ethnic groups, results in diffuse pigmentation. Outside of Africa, it may be
      misinterpreted as racial pigmentation or pose a diagnostic puzzle. The color and
      distribution pattern of diffuse gingival pigmentation often are quite suggestive,
      and the clinical diagnosis should be confirmed by patient history. In selected
      cases, biopsy may be necessary to exclude other diagnostic considerations.

PMID- 17199556
TI  - Treatment of gingival hyperpigmentation by erbium-doped:yttrium, aluminum, and
      garnet laser for esthetic purposes.
AB  - BACKGROUND: The normal color of gingiva is pink. Gingival hyperpigmentation is
      mostly caused by the physiologic deposition of melanin by melanocytes. In "gummy
      smile" patients, melanin gingival hyperpigmentation causes an esthetic problem
      and may cause physiologic disturbances. Methods to remove gingival
      hyperpigmentation vary, but it seems that the most reliable and satisfactory
      procedure is laser ablation. METHODS: Six white patients (five females and one
      male), who complain of having dark-brown to black gingival hyperpigmentation were
      included in the study. Three of them were smokers. Laser ablation was performed
      by an erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser (settings: 250
      mJ, 15 Hz, with water and air and using the defocused mode) without using topical
      or local anesthesia. Each patient required about 20 to 25 minutes for completion
      of the procedure. After 4 days, another laser ablation (with the same previous
      settings) was performed to ensure good results. Patients were evaluated a month
      after completion of treatment and on a semiannual basis. The follow-up period
      ranged between 6 and 18 months. RESULTS: In all patients, no discomfort, pain, or
      bleeding complications were found intraoperatively or 4 days postoperatively.
      Ablated wounds healed almost completely within 4 days. No recurrence of gingival
      hyperpigmentation was found during the follow-up periods. Achieved results were
      satisfactory for patients and the operator. CONCLUSIONS: Taking into account the
      advantages of using lasers, it seems to be that the depigmentation of melanin
      hyperpigmented gingiva by the Er:YAG laser is a reliable and satisfactory
      procedure. Esthetic results were satisfactory for patients and the operator, and
      no repigmentation was found during the follow-up period.

PMID- 17199557
TI  - Surgical treatment of infrabony defects with autologous platelet concentrate or
      bioabsorbable barrier membrane: a prospective case series.
AB  - BACKGROUND: Autologous platelet concentrate (APC) contains concentrated platelet
      derived growth factors that promote wound healing and tissue regeneration. The
      purpose of this prospective case series was to compare the treatment effects of
      an intralesional graft of APC to guided periodontal regeneration (GPR) using a
      bioabsorbable barrier membrane (MEM) over a 52-week period. METHODS: Five
      patients were recruited for the study from two private periodontal practices.
      There were four females and one male having a mean age of 33 +/- 10.23 years. The
      five selected contralateral teeth had similar, but not identical, combinations of
      1-, 2-, and 3-wall infrabony defects not involving furcations. Probing depths
      (PDs) of the defects were > or = 6 mm and had radiographic angular infrabony
      defects > or = 4 mm in depth. The patients had no local or systemic
      contraindications to minor oral surgical procedures and had not taken systemic
      antibiotics for > or = 6 months before the commencement of the study. All
      patients had completed cause-related periodontal therapy up to 6 months
      previously and had achieved a satisfactory level of oral hygiene. The selected
      teeth did not have purulent discharge from the pockets and responded normally to
      pulp sensibility testing. Patients were excluded if they smoked, were pregnant or
      lactating, or were allergic to any of the materials to be used in the treatment.
      At baseline and 8, 26, and 52 weeks after surgery, PDs, recession (REC), presence
      of plaque, and bleeding on probing were recorded, and standardized periapical
      radiographs were taken. At the time of surgery, the vertical distance to the
      deepest point of the infrabony defect was measured from the cemento-enamel
      junction (CEJ) to the buccal and lingual bone crests. The vertical distance to
      the base of the defect from the CEJ and defect angles were obtained from
      radiographs. The paired contralateral infrabony defects were treated with a graft
      APC or MEM after debridement and EDTA root surface conditioning. Surgical flaps
      were prepared and closed according to the papilla preservation method. Post
      surgical care was provided at 1, 2, 8, 26, and 52 weeks after surgery. A
      mouthwash of 0.2% chlorhexidine gluconate was used twice daily for the first 3
      weeks after surgery. Mean PD, REC, clinical attachment level (CAL), radiographic
      bone loss, and defect angle were computed and compared for each data collection
      point. RESULTS: From baseline to 52 weeks, a mean PD reduction of 3 +/- 1.41 mm
      (APC) and 3.6 +/- 1.67 mm (MEM), mean REC increase of 0.8 +/- 1.01 mm (APC) and
      0.6 +/- 1.14 mm (MEM), mean CAL gain of 2.2 +/- 1.79 mm (APC) and 3 +/- 1 mm
      (MEM), mean radiographic bone fill of 3.24 +/- 2.85 mm (APC) and 2.7 +/- 1.9 mm
      (MEM), and mean defect-angle increase of 15.25 degrees +/- 18.21 degrees (APC)
      and 22.4 degrees +/- 27.3 degrees (MEM) were calculated. CAL gain was not related
      clearly to defect angle at baseline, although radiographic bone fill was slightly
      greater for defect angles <39.4 degrees +/- 7.88 degrees. CONCLUSIONS: This case
      series of five similar, but not identical, bilateral paired infrabony defects
      suggests that an APC graft achieves a similar CAL gain and PD reduction to GPR
      using an MEM over a 52-week period. A larger, controlled clinical trial is needed
      to evaluate further the efficacy of autologous platelet-rich plasma for the
      treatment of infrabony defects.

PMID- 17199558
TI  - Immunopathogenesis in hepatitis C virus cirrhosis.
AB  - HCV (hepatitis C virus) has a high propensity to persist and to cause chronic
      hepatitis C, eventually leading to cirrhosis. Since HCV itself is not cytopathic,
      liver damage in chronic hepatitis C is commonly attributed to immune-mediated
      mechanisms. HCV proteins interact with several pathways in the host's immune
      response and disrupt pathogen-associated pattern recognition pathways, interfere
      with cellular immunoregulation via CD81 binding and subvert the activity of NK
      (natural killer) cells as well as CD4(+) and CD8(+) T-cells. Finally, HCV
      specific T-cells become increasingly unresponsive and apparently disappear, owing
      to several possible mechanisms, such as escape mutations in critical viral
      epitopes, lack of sufficient help, clonal anergy or expansion of regulatory T
      cells. The role of neutralizing antibodies remains uncertain, although it is
      still possible that humoral immunity contributes to bystander damage of virally
      coated cells via antibody-dependent cellular cytotoxicity. Cytotoxic lymphocytes
      kill HCV-infected cells via the perforin/granzyme pathway, but also release Fas
      ligand and inflammatory cytokines such as IFNgamma (interferon gamma). Release of
      soluble effector molecules helps to control HCV infection, but may also destroy
      uninfected liver cells and can attract further lymphocytes without HCV
      specificity to invade the liver. Bystander damage of these non-specific
      inflammatory cells will expand the tissue damage triggered by HCV infection and
      ultimately activate fibrogenesis. A clear understanding of these processes will
      eventually help to develop novel treatment strategies for HCV liver disease,
      independent from direct inhibition of HCV replication.

PMID- 17199559
TI  - Initial orthostatic hypotension: review of a forgotten condition.
AB  - Several studies have shown that standing up is a frequent (3-10%) trigger of loss
      of consciousness both in young and old subjects. An exaggerated transient BP
      (blood pressure) fall upon standing is the underlying cause. IOH (initial
      orthostatic hypotension) is defined as a transient BP decrease within 15 s after
      standing, >40 mmHg SBP (systolic BP) and/or >20 mmHg DBP (diastolic BP) with
      symptoms of cerebral hypoperfusion. It differs distinctly from typical
      orthostatic hypotension (i.e. BP decrease >20 mmHg SBP and/or >10 mmHg DBP after
      3 min of standing) as the BP decrease is transient. Only continuous beat-to-beat
      BP measurement during an active standing-up manoeuvre can document this
      condition. As IOH is only associated with active rising, passive tilting is of no
      diagnostic value. The pathophysiology of IOH is thought to be a temporal mismatch
      between cardiac output and vascular resistance. The marked decrease of vascular
      resistance during rising is similar to that observed at the onset of leg exercise
      and is absent during head-up tilting. It is attributed to vasodilatation in the
      working muscle through local mechanisms. Standing up causes an initial increase
      in venous return through the effects of contraction of leg and abdominal muscles.
      The consequent sudden increase in right atrial pressure may contribute to the
      fall in systemic vascular resistance through a reflex effect. This review alerts
      clinicians and clinician scientists to a common, yet often neglected, condition
      that occurs only upon an active change of posture and discusses its epidemiology,
      pathophysiology and management.

PMID- 17199560
TI  - Mycosis fungoides: a dermatological masquerader.
AB  - Mycosis fungoides (MF), a low-grade lymphoproliferative disorder, is the most
      common type of cutaneous T-cell lymphoma. Typically, neoplastic T cells localize
      to the skin and produce patches, plaques, tumours or erythroderma. Diagnosis of
      MF can be difficult due to highly variable presentations and the sometimes
      nonspecific nature of histological findings. Molecular biology has improved the
      diagnostic accuracy. Nevertheless, clinical experience is of substantial
      importance as MF can resemble a wide variety of skin diseases. We performed a
      literature review and found that MF can mimic >50 different clinical entities. We
      present a structured framework of clinical variations of classical, unusual and
      distinct forms of MF. Distinct subforms such as ichthyotic MF, adnexotropic
      (including syringotropic and folliculotropic) MF, MF with follicular mucinosis,
      granulomatous MF with granulomatous slack skin and papuloerythroderma of Ofuji
      are delineated in more detail.

PMID- 17199561
TI  - Guidelines for management of Bowen's disease: 2006 update.
AB  - This article represents a planned regular updating of the previous British
      Association of Dermatologists (BAD) guidelines for management of Bowen's disease.
      They have been prepared for dermatologists on behalf of the BAD. They present
      evidence-based guidance for treatment, with identification of the strength of
      evidence available at the time of preparation of the guidelines.

PMID- 17199562
TI  - Temporal changes in sebum excretion and propionibacterial colonization in
      preadolescent children with and without acne.
AB  - BACKGROUND: It is generally accepted that the onset of sebum secretion occurs
      before puberty in boys and girls as a result of increasing androgen output during
      the adrenarche. Propionibacteria are part of the commensal skin flora and, in
      adults, are found in highest numbers in sebum-rich areas of skin such as the face
      and upper trunk. Previous studies investigating the association between sebum
      output and propionibacterial population densities have been cross-sectional and
      have been carried out mainly in adults. OBJECTIVES: The purpose of this study was
      to examine the association between the onset of sebum secretion and expansion of
      the propionibacterial flora in a population of early adolescent children aged
      between 5.5 and 12 years, and to evaluate the temporal relation between the two
      factors longitudinally. In addition, the study aimed to evaluate the change with
      age in sebaceous gland activity and propionibacterial colonization on the skin
      and in the nares between children who developed acne and those who did not.
      METHODS: Biannual examinations of volunteers included age, pubertal (Tanner)
      stage, weight and height, lesion counting on the face, propionibacterial
      colonization on the skin surface and in the nares and sebum secretion. A
      longitudinal analysis based on all observations of each subject throughout the
      study was applied to examine the change of sebaceous gland activity and
      propionibacterial colonization with age and pubertal stage. A generalized
      estimating equation was used with a 0.05 level of significance. RESULTS: The
      commencement of sebum production was asynchronous, with only a small number of
      follicles initially starting to secrete sebum onto the skin surface. The number
      of secreting follicles and the area of sebum increased with age and pubertal
      stage (P < 0.0001, P < 0.05, respectively). Numbers of propionibacteria on the
      skin tended to increase after the age of 9 years, but not significantly so. In
      contrast, numbers of propionibacteria in the nares increased significantly with
      age (P < 0.0001) but not with pubertal maturation. Children who developed acne
      had higher sebum output and propionibacterial densities with increasing age than
      children who did not develop acne. This effect was significant for the increase
      of total sebum area with age in pubertal children (P = 0.0023), the increase in
      number of secreting follicles with age (P = 0.020) in prepubertal children, and
      the increase in propionibacteria densities in the nares with age (P = 0.0005) in
      pubertal children. Sebaceous gland activity and propionibacterial numbers on the
      skin surface remained unchanged with increasing age in children who did not
      develop acne. Propionibacterial population densities in the nares increased with
      age regardless of the development of acne. CONCLUSIONS: Onset of sebum secretion
      and consequently expansion of the propionibacterial skin flora occur earlier in
      children who develop acne than in children of the same age and pubertal status
      who do not develop acne. These observations suggest that postponing the onset of
      sebum production or the expansion of the propionibacterial skin flora until after
      puberty may represent ways of preventing the disease or minimizing its severity.
      Determinants of propionibacterial colonization on the skin and in the nares may
      be different.

PMID- 17199563
TI  - The role of heat shock protein 60, vascular endothelial growth factor and
      antiphospholipid antibodies in Behcet disease.
AB  - BACKGROUND: Behcet disease is a systemic inflammatory disease of unknown
      aetiology. T cells in this disease proliferate vigorously in response to a
      specific peptide of heat shock protein (HSP) 60 in an antigen-specific fashion.
      Vascular endothelial cell growth factor (VEGF) is a cytokine participating in the
      inflammatory process. One of the prominent features of Behcet disease is
      vasculitis as a result of endothelial dysfunction. Antiphospholipid antibodies
      (APA) may play a role in the development of thrombosis by inhibiting production
      of prostacyclin by endothelial cells. OBJECTIVES: To investigate the role of
      HSP60, VEGF and APA in Behcet disease and their relation to clinical
      manifestations and disease activity. METHODS: Thirty patients with Behcet disease
      were included; 17 were in the active stage and 13 were in the inactive. Fifteen
      age- and sex-matched healthy subjects served as controls. Complete clinical
      examination and Doppler examination were done. Serum levels of HSP60, VEGF and
      APA were performed. RESULTS: Serum levels of HSP60, VEGF and APA were
      significantly higher in patients than in controls; however, their level did not
      correlate with disease activity. The serum level of VEGF correlated significantly
      with the presence of vascular manifestations and ocular involvement. The serum
      level of APA was greater in patients with thrombosis. HSP60 has an important role
      in aetiopathogenesis of Behcet disease, which sheds new light on its autoimmune
      nature. CONCLUSIONS: An elevated serum level of VEGF may be a risk factor for the
      development of ocular disease contributing to poor visual outcome.

PMID- 17199564
TI  - Assessment of the presence of mucosal human papillomaviruses in malignant
      melanomas using combined fluorescent in situ hybridization and chemiluminescent
      immunohistochemistry.
AB  - BACKGROUND: The vast majority of studies aimed at detecting human papillomavirus
      (HPV) DNA in skin cancer have used sensitive polymerase chain reaction (PCR)
      methods but the PCR technique, despite its high sensitivity, is not suitable to
      ascertain whether (i) the presence of HPV can be related only to few cells
      harbouring the virus, (ii) the presence of HPV is due to a tumour surface
      contamination and (iii) the presence of HPV is localized in cancer cells, rather
      than in normal keratinocytes present in the tumour biopsy. In a recent work we
      have found mucosal high-risk (HR) HPV genotypes in primary melanoma by PCR.
      OBJECTIVES: To localize mucosal HR-HPV nucleic acids and tumoural melanocytic
      marker in the same sections of primary melanoma samples in order to understand
      the relationship between HPVs and melanoma cells. METHODS: We have developed a
      very sensitive method that combines an enzyme-amplified fluorescent in situ
      hybridization (ISH) for the detection of HPV nucleic acids (types 16 and 18) with
      a chemiluminescent immunohistochemistry (IHC) method for the detection of the
      tumoural melanocytic marker HMB-45 sequentially in the same section. Digital
      images of fluorescent ISH and chemiluminescent IHC were separately recorded,
      assigned different colours and merged using specific software for image analysis.
      RESULTS: The combined fluorescent ISH and chemiluminescent IHC demonstrated a
      sharp colocalization (in the range 60-80%) of HPV nucleic acids and melanoma
      marker inside the same sections of melanoma biopsies, with a strong specificity
      and sensitivity. CONCLUSIONS: The strong colocalization of mucosal HR-HPV nucleic
      acids and HMB-45 melanocytic marker emphasized that viral nucleic acids were
      specifically present in melanoma cells and supported a possible active role of
      HPV in malignant melanoma.

PMID- 17199565
TI  - Skin surveillance of a U.K. paediatric transplant population.
AB  - BACKGROUND: Solid organ transplant recipients are at increased risk of skin
      cancer. Melanoma is less common than nonmelanoma skin cancer (NMSC) although the
      relative proportion of melanoma among skin cancers has been shown to be higher in
      paediatric than adult recipients. Multiple melanocytic naevi and/or atypical
      naevi may be a risk factor for the development of melanoma. The relationship
      between naevus counts and phenotypic characteristics, disease-related variables
      and sun exposure has not been explored in paediatric transplant patients.
      OBJECTIVES: To determine the prevalence of premalignant and malignant skin
      lesions and to identify known risk factors associated with benign and atypical
      melanocytic naevi in a U.K. paediatric transplant population. METHODS: Paediatric
      (< or = 19 years) renal and liver transplant patients, who were 5 or more years
      post-transplantation, were reviewed over 12 months. Lifetime history of sun
      exposure, episodes of sunburn, sunny holidays, sunscreen use, sun bed use,
      demographic and transplantation details were collected using interview,
      questionnaire and case note review. A skin examination was performed for regional
      counts of malignant lesions, benign and atypical naevi. RESULTS: Ninety-eight
      patients (82 liver, 13 renal, three multiorgan) with a median follow up of 9
      years (range 5-16) were reviewed. Neither skin cancer nor premalignant lesions
      for NMSC were detected in this group. Eighty-five patients had benign naevi
      (median 6, range 1-57). Clinical risk factors for increased counts of benign
      naevi included increasing age (P = 0.03), more episodes of sunburn (P = 0.003)
      and prolonged treatment with cyclosporin (P = 0.009). The presence of atypical
      naevi in six patients was significantly associated with more episodes of sunburn
      (P = 0.006) and more transplants (P = 0.04). Other variables including phenotype,
      skin type, sun exposure, holidays abroad, residence abroad and total duration of
      immunosuppression did not correlate with benign or atypical naevus counts.
      CONCLUSIONS: Skin cancer was not observed in paediatric solid organ transplant
      recipients who were 5-16 years post-transplantation. Both benign and atypical
      naevus counts were higher in children with frequent episodes of sunburn. As both
      naevi and sunburn are risk factors for melanoma, we should target fair-skinned
      transplant recipients with naevi for intensive sun avoidance education. A
      prospective, longitudinal follow-up study should determine the onset of skin
      cancer post-transplantation and the significance of benign and atypical naevus
      counts in this cohort.

PMID- 17199566
TI  - Altered innate and adaptive immune responses in patients with hidradenitis
      suppurativa.
AB  - BACKGROUND: The clinical improvement of hidradenitis suppurativa reported in a
      small number of patients with antitumour necrosis factor (anti-TNF)-alpha
      therapies supports the hypothesis for an altered immune response in these
      patients. OBJECTIVES: To evaluate the state of the innate and adaptive immune
      responses in patients with hidradenitis suppurativa. METHODS: Fifty-three
      patients and six healthy controls were studied. Blood was sampled and
      subpopulations of lymphocytes were analysed by flow cytometry; monocytes were
      isolated and their function was evaluated from the concentrations of TNF-alpha
      and interleukin (IL)-6 in supernatants of cell cultures after triggering with
      endotoxins (lipopolysaccharides). TNF-alpha and IL-6 were estimated by an enzyme
      immunoassay. RESULTS: CD3/CD8 lymphocytes were lower in patients with involvement
      of the perineum than in controls; patients with involvement of the breast had
      higher levels of natural killer (NK) cells than controls. A negative correlation
      was found between years lapsing since initial presentation of lesions of
      hidradenitis and the percentage of NK cells. Monocytes isolated from healthy
      volunteers were more active for the secretion of TNF-alpha and IL-6 than those of
      patients with hidradenitis suppurativa. CONCLUSIONS: A reduction in the
      percentage of NK cells over time and a lower monocyte response to triggering by
      bacterial components is observed in patients with hidradenitis suppurativa.
      Further research is needed to clarify if these changes are connected to an
      autoimmune mechanism in the pathogenesis of hidradenitis suppurativa.

PMID- 17199567
TI  - Does adjuvant alpha-interferon improve outcome when combined with total skin
      irradiation for mycosis fungoides?
AB  - BACKGROUND: Patients with mycosis fungoides (MF) experience frequent disease
      recurrences following total skin electron irradiation (TSEI) and may benefit from
      adjuvant therapy. OBJECTIVES: To review the McGill experience with adjuvant alpha
      interferon (IFN) in the treatment of MF. METHODS: From 1990 to 2000, 50 patients
      with MF were treated with TSEI: 31 with TSEI alone and 19 with TSEI + IFN. Median
      TSEI dose was 35 Gy. In the TSEI + IFN group, IFN was given subcutaneously at 3 x
      10(6) units three times per week starting 2 weeks prior to start of TSEI,
      continued concurrently with the radiation and for an additional 12 months
      following TSEI. The TSEI alone group included 16 men and 15 women with a median
      age of 61 years (range 31-84). The TSEI + IFN group included 14 men and five
      women with a median age of 51 years (range 24-83). Clinical stage was IA, IB,
      IIA, IIB, III and IVA in 2, 9, 4, 8, 1 and 7 patients of the TSEI group and 0, 3,
      3, 7, 4 and 2 patients of the TSEI + IFN group. RESULTS: Median follow up for
      living patients was 70 months. All patients responded to treatment. Complete
      response (CR) rate was 65% following TSEI and 58% following TSEI + IFN (P = 0.6).
      Median overall survival (OS) was 61 months following TSEI and 38 months following
      TSEI + IFN (P = 0.4). Acute grade II-III dermatitis was seen in all patients.
      Fever, chills or myalgia were seen in 32% of patients treated with TSEI + IFN.
      CONCLUSIONS: Concurrent IFN and TSEI is feasible, with acceptable toxicity. Even
      when controlling for disease stage, the addition of IFN did not appear to
      increase CR rate, disease-free survival or OS.

PMID- 17199568
TI  - Transcriptional profiles in melanocytes from clinically unaffected skin
      distinguish the neoplastic growth pattern in patients with melanoma.
AB  - BACKGROUND: It is generally accepted that sunlight may contribute to the
      development of melanoma. OBJECTIVES: To analyse gene expression of melanocytes
      obtained from clinically unaffected skin of patients with melanoma and healthy
      controls before and after exposure to ultraviolet B radiation. METHODS: Using
      GeneChip array technology, the gene expression of melanocytes obtained from the
      two donor groups was profiled, in order to identify transcriptional differences
      affecting susceptibility to melanoma. RESULTS: The data collected did not show
      any difference between the expression profiles of melanocytes purified from
      normal donors and from patients with melanoma that was able to give a
      statistically significant class separation. However, by means of unsupervised
      clustering our data could be divided into two main classes. The first class
      included the transcriptome profiles of melanocytes obtained from skin samples of
      patients with a vertical growth phase (VGP) melanoma, while the second class
      included the transcriptome profiles of melanocytes obtained from skin samples of
      patients with a radial growth phase (RGP) melanoma. CONCLUSIONS: These data
      suggest that melanocytes in patients with VGP and RGP melanomas show significant
      differences in gene expression profiles, which allow us to classify patients with
      melanoma also from clinically unaffected skin.

PMID- 17199569
TI  - Melanomas arising from naevi and de novo melanomas--does origin matter?
AB  - BACKGROUND: It is widely accepted that some melanomas arise from pre-existing
      naevi, while others appear de novo. The proportions involved and the effect of
      melanoma origin on prognosis is unclear. OBJECTIVES: To determine whether
      melanomas reported by the patient to have developed from a pre-existing naevus
      are associated with a better or worse prognosis compared with those arising de
      novo when adjusted for confounding variables. METHODS: All patients attending a
      dedicated melanoma screening clinic between March 1997 and March 2002 were
      included. The distinction between melanoma arising without any pre-existing
      lesion (de novo) and those derived from a pre-existing lesion (naevus melanoma)
      was based on patient history. We categorized patients into three groups: those
      who gave a history of their lesion arising within a pre-existing naevus, those in
      whom the melanoma developed de novo and those in whom no conclusive history could
      be obtained. We compared prognostic indicators between the naevus and de novo
      melanoma groups. RESULTS: Of 8593 patients screened, 377 had a positive diagnosis
      of melanoma (in situ or invasive). Of these 42% had naevus melanomas, 34% new
      melanomas and 24% were uncertain. Patients presenting with a melanoma arising
      from a pre-existing naevus had a greater Breslow thickness despite presenting
      sooner than the de novo group, although no significant difference in thickness
      was found when other prognostic factors were controlled for. CONCLUSIONS: This
      prospective study shows that naevi that undergo malignant change may result in
      melanomas that are thicker and thus potentially have a worse prognosis than de
      novo melanomas. Although our results were not statistically significant when
      other risk factors were also taken into account, it is possible that a larger
      study would identify a significant association.

PMID- 17199570
TI  - Severity of hand eczema assessed by patients and dermatologist using a
      photographic guide.
AB  - BACKGROUND: The severity of hand eczema is of interest in epidemiological
      studies. Ideally, as no validated methods of self-assessment exist, a
      dermatologist should examine all subjects. However, this is very resource
      intensive. OBJECTIVES: To examine if severity grading performed by patients with
      hand eczema using a self-administered photographic guide was in agreement with
      the assessment performed by a trained dermatologist. Furthermore, to measure the
      correlation between the severity of hand eczema expressed on a visual analogue
      scale (VAS) and the clinical severity assessment, using the photographic guide.
      METHODS: Fifty-three consecutive outpatients with hand eczema were included, a
      number based on a prestudy statistical calculation. The patients were asked to
      grade current severity of their hand eczema by choosing one of four groups of
      photographs representing differing severities of hand eczema. On the same day all
      patients were examined by an experienced dermatologist, who graded the severity
      using the same photographic guide. The photographic guide was a modified version
      of a validated guide for use by physicians. In addition, the patients rated the
      severity of their hand eczema on a VAS. RESULTS: Fifty-one of the respondents
      completed the full questionnaire. For 37 of the 51 patients (73%) the clinical
      severity assessments of patient and dermatologist were identical. The measure of
      agreement, Cohen's kappa coefficient, was 0.61, indicating good inter-rater
      agreement. The correlation between the dermatologist-rated severity and the
      corresponding score by the patients on the VAS was only moderate (Spearman's rank
      correlation coefficient rho = 0.52). CONCLUSIONS: The photographic guide for the
      self-assessment of hand eczema is an easy instrument to use, and for research
      purposes can be a reliable tool for patients with hand eczema to grade severity.
      A VAS can only be considered as a mediocre tool for estimation of the
      dermatologist-rated clinical severity, but should be validated as an independent
      instrument to assess severity of hand eczema.

PMID- 17199571
TI  - The use of confocal laser-scanning microscopy in microsurgery for invasive
      squamous cell carcinoma.
AB  - BACKGROUND: Ex-vivo confocal laser-scanning microscopy offers rapid imaging of
      excised tissue specimens without conventional histotechnical procedures. As
      vertical sections are prepared, morphological features can be assessed according
      to standard criteria used in conventional histopathology. OBJECTIVES: To validate
      the diagnostic confocal examination of squamous cell carcinoma (SCC) in
      microscopy-guided surgery. METHODS: Four independent observers received
      standardized instructions about diagnostic confocal microscopy features of SCC.
      Subsequently, 120 confocal images of fresh excisions from SCC or normal skin,
      imaged using a commercially available, near-infrared, reflectance confocal laser
      scanning microscope, were evaluated by each observer. RESULTS: General
      morphology, such as location, size and shape of the cancer area could be
      visualized by the imaging system. Furthermore, densely packed and irregularly
      organized nuclei and nuclear atypia could be delineated. Overall, a sensitivity
      of 95% and a specificity of 96.25% were achieved by the four observers (positive
      predictive value 96.25%, negative predictive value 95.23%). CONCLUSIONS: This
      study provides a set of well-described morphological criteria with obvious
      diagnostic impact which should be used in further investigations. In the future,
      confocal laser-scanning microscopy may guide microsurgery of any skin cancer.

PMID- 17199572
TI  - Effect of smoking on skin elastic fibres: morphometric and immunohistochemical
      analysis.
AB  - BACKGROUND: It has been established during recent years that smoking is an
      independent risk factor for the development of premature facial wrinkling. The
      underlying mechanism is not well known, but elastic fibres of the dermis seem to
      be the major target of smoke components. OBJECTIVES: To determine quantitative
      and qualitative changes of the dermal elastic tissue of non-sun-exposed skin
      induced by smoking, as well as the possible mechanisms responsible for them.
      METHODS: Sixty-nine patients were recruited (20 nonsmokers, 19 former smokers and
      30 smokers). Using static morphometry and immunohistochemistry and lectin
      staining we analysed elastic fibres of the dermis and their major components,
      elastin and microfibrillar component. RESULTS: Significantly higher values for
      the number of elastic fibres mm(-2) and the percentage of the area filled by them
      in the reticular dermis were found in smokers. Cumulative tobacco dose showed
      statistically significant correlations with both morphological parameters
      (Spearman's rank correlation coefficient). Immunohistochemistry demonstrated that
      the two main components of elastic fibres were altered in smokers. Plasma
      protease inhibitors and lectin staining were negative in all the samples.
      CONCLUSIONS: Smoking is an independent risk factor for the increase of elastic
      fibres in the reticular dermis of nonexposed skin, and it acts on their two main
      structural components, elastin and microfibrillar component. This increase in the
      area of elastic fibres in smokers is not due to newly synthesized elastic
      material, but to their degradation, as occurs in solar elastosis and which acts
      in an additive manner.

PMID- 17199573
TI  - Characterization of the expression and activation of the epidermal growth factor
      receptor in squamous cell carcinoma of the skin.
AB  - BACKGROUND: Locally advanced skin cancers including squamous cell carcinoma (SCC)
      of the skin are increasing in incidence. Patients are often elderly with
      significant comorbidities and therapy can be difficult. New targeted therapies,
      such as treatment directed at the epidermal growth factor receptor (EGFR), may be
      effective and less toxic in these patients. However, before designing appropriate
      clinical trials it is necessary to characterize the expression and activation of
      targets such as the EGFR to evaluate the rationale of using EGFR inhibitors
      (EGFRIs) in the treatment of this type of cancer. OBJECTIVES: To characterize the
      expression and activation by phosphorylation of EGFR in SCC of the skin by
      quantitative Western blotting using the LiCor immunofluorescence detection system
      with validation by immunohistochemistry. Secondary objectives were to evaluate
      downstream targets of EGFR expression and activation in SCC of the skin and to
      examine the associations between EGFR, pathological features and clinical
      behaviour of these tumours. METHODS: Twenty-one mainly locally advanced skin SCCs
      collected in our institution and stored in our tissue bank over a 4-year period
      were used for the study. RESULTS: Nine of 21 (43%) tumours expressed EGFR above
      background. Of those nine, five expressed phosphorylated EGFR. There was no
      correlation with downstream activation of canonical signalling pathways,
      pathological features or clinical behaviour. CONCLUSIONS: EGFR is expressed in a
      minority of tumours and then is not always activated. These results show that,
      before designing a trial with a targeted agent such as an EGFRI in SCC of the
      skin, it is important to verify the presence of the appropriate target to
      maximize the best outcome.

PMID- 17199574
TI  - The risk for cutaneous malignant melanoma, melanoma in situ and intraocular
      malignant melanoma in relation to tobacco use and body mass index.
AB  - BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) and melanoma in
      situ (MIS) has been increasing during the last 50 years. Malignant melanoma (MM)
      is also the most common intraocular malignancy (IMM). Besides ultraviolet
      radiation, the cause of these tumours is largely unknown. OBJECTIVES: We designed
      a study to examine the effect of body mass index (BMI) and tobacco use on the
      risk for MM and MIS. METHODS: Analyses were performed on a nationwide cohort of
      339 802 Swedish construction workers. Exposure information was collected
      prospectively by questionnaires combined with personal interviews. RESULTS:
      Follow up yielded a total of 7 663 400 person-years during which 1639 workers
      developed MM/MIS. The risk for MM/MIS was reduced in current or previous smokers
      compared with those who had never smoked, both when analysing all smoking tobacco
      products combined and when analysing cigarette and pipe smokers separately. The
      risk was further diminished with longer duration of smoking and greater quantity
      of tobacco smoked. The effect was more evident in CMM/MIS than in IMM. Snuff
      taking conferred a decreased risk for CMM/MIS, and a BMI over normal weight range
      conferred an increased risk for CMM. CONCLUSIONS: Tobacco smoking was found to be
      inversely associated with the risk for CMM and MIS. The mechanism of action is
      unknown but it has been suggested to be due to the immune suppressive effect that
      tobacco exerts which would be protective against deleterious immune reactions
      caused by, for example, the sun. Neither is the mechanism behind the higher risk
      for CMM due to being overweight known. One hypothesis is that it is an effect of
      a hormonal imbalance. Further studies are required to elucidate these mechanisms.

PMID- 17199575
TI  - Characteristics and completeness of clinical trial registrations in psoriasis and
      atopic dermatitis.
AB  - BACKGROUND: Controversy over the failure to publish results of clinical trials
      linking antidepressant treatment to suicidal behaviour in adolescents has
      increased interest in clinical trial registration. OBJECTIVE: To assess numbers,
      characteristics and completeness of registrations of trials for psoriasis and
      atopic dermatitis registered at two web-based trial registries:
      ClinicalTrials.gov and isrctn.org. METHODS: In this cross-sectional study we
      identified trials by searching ClinicalTrials.gov and isrctn.org on 18 January
      2006 for trials registered up to 31 December 2005. We included only trials of
      therapeutic interventions for atopic dermatitis or psoriasis. We ascertained the
      date of submission of registration, the funding source of the trial, and whether
      a registration listed the specific name of the intervention studied, the specific
      outcome measure used (e.g. "Psoriasis Area and Severity Index"), the criterion
      used to gauge success on the outcome measure (e.g. > or = 75% decrease), and the
      time at which the outcome would be assessed (e.g. at 12 weeks). RESULTS: There
      were 156 registered trials, including 128 (82%) at ClinicalTrials.gov [36 (23%)
      in atopic dermatitis, 92 (59%) in psoriasis] and 28 (18%) at isrctn.org [23 (15%)
      in atopic dermatitis, 5 (3%) in psoriasis]. Pharmaceutical companies funded 87
      trials (56%), federal or governmental agencies 28 (18%), universities or
      organizations 21 (13%), and a combination of funders 20 (13%). Of atopic
      dermatitis trials (13 of 36) and (24 of 92) of psoriasis trials at
      ClinicalTrials.gov were registered in September 2005. The specific name of the
      intervention studied was listed in 150 registrations (96%), 89 (57%) listed the
      specific measure used, 69 (44%) listed the criteria to gauge success and 62 (40%)
      listed the time of assessment. CONCLUSIONS: While trial registrations in atopic
      dermatitis and psoriasis are increasing, more complete information in these
      registrations may increase their value for dermatologists and their patients.

PMID- 17199576
TI  - Validation of the U.K. Working Party diagnostic criteria for atopic eczema in a
      Xhosa-speaking African population.
AB  - BACKGROUND: Reliable diagnostic criteria for eczema are important for
      epidemiological comparisons. Although the U.K. diagnostic criteria for atopic
      eczema have performed well in an English language setting, limited data are
      available from other countries where cultural and linguistic factors may affect
      their validity. OBJECTIVES: We sought to determine the validity of the U.K.
      criteria for eczema in relation to clinical assessment by a dermatologist in a
      Xhosa-speaking South African population. METHODS: A cross-sectional survey of
      3067 children aged 3-11 years was conducted in rural, peri-urban and urban
      settings in South Africa. The prevalence of atopic eczema was determined using
      the U.K. diagnostic criteria and a clinical assessment by a dermatologist.
      Questions were translated into the local language (Xhosa). Trained researchers
      administered the questions to the children's parents or carers. The validity of
      the U.K. criteria was then determined by calculating the sensitivity,
      specificity, positive and negative predictive values, and Youden's Index in
      relation to the dermatologist's examination. RESULTS: The point prevalence of
      atopic eczema according to a dermatologist was 1.0% [95% confidence interval (CI)
      0.6-1.4], while the prevalence of visible flexural eczema according to the U.K.
      protocol was 1.8% (95% CI 1.3-2.2). The sensitivity and specificity of the U.K.
      criteria in this setting was 43.7% (95% CI 26.3-62.3) and 97.9% (97.3-98.4),
      respectively. The positive and negative predictive values of the U.K. criteria
      were 18.4% (95% CI 10.4-28.9) and 99.4% (95% CI 99.0-99.6), respectively. The
      presence of visible flexural eczema according to the U.K. photographic protocol
      was the best predictor of atopic eczema, with a sensitivity and specificity of
      81.2% (95% CI 63.5-92.7) and 99.0% (95% CI 98.6-99.3), respectively, and a
      positive and negative predictive value of 48.1% (95% CI 34.3-62.1) and 99.8% (95%
      CI 99.5-99.9), respectively. CONCLUSIONS: The validity of the full question-based
      version of the U.K. diagnostic criteria for atopic eczema in this South African
      setting is low, which may be due to a combination of translational and cultural
      issues. However, the one physical sign of visible flexural eczema performed well,
      suggesting that it alone might be a useful tool for future international
      comparative prevalence studies.

PMID- 17199577
TI  - Photodegradation of folic acid during extracorporeal photopheresis.
AB  - BACKGROUND: Photodegradation of folic acid (FA) by ultraviolet (UV) radiation is
      a well-documented photochemical reaction, and decreased serum levels of FA have
      been found in patients receiving photochemotherapy (psoralen plus UVA). During
      extracorporeal photopheresis (ECP) leucocytes and plasma are subjected to 8
      methoxypsoralen (8-MOP) plus UVA. OBJECTIVES: To investigate whether ECP leads to
      the photodegradation of FA in the extracorporeal system. METHODS: In 30 patients
      undergoing ECP on two consecutive days the FA levels were measured in the
      extracorporeal collected plasma prior to and after UVA exposure. Healthy donor
      plasma was exposed to 8-MOP and increasing doses of UVA in vitro. In five
      patients serum folate levels were determined before and after ECP. RESULTS: We
      found a mean reduction of 44% and 46% on the first and second day of treatment,
      respectively. This effect could be reproduced in vitro: the irradiation of
      healthy donor plasma with UVA led to a dose-dependent reduction of FA of up to
      54.75% at 16 J cm(-2). This was independent of the presence of 8-MOP and the base
      concentration of 5-methyltetrahydrofolate; minimal changes were observed for
      vitamin B(12) and homocysteine, not undergoing photodegradation. Serum folate
      levels did not change significantly before and after ECP. CONCLUSIONS: We
      conclude that extracorporeal exposure of plasma to UVA during ECP leads to
      photodegradation of FA. Further investigations are required to determine the
      biological effects of folate photoproducts and whether clinically relevant loss
      of FA might be a consequence of ECP.

PMID- 17199578
TI  - Effects of psoralen plus ultraviolet A irradiation on cultured epidermal cells in
      vitro and patients with vitiligo in vivo.
AB  - BACKGROUND: Both psoralen plus ultraviolet (UV) A (PUVA) and narrowband UVB (NB
      UVB) irradiation are effective treatments for vitiligo vulgaris. However, the
      mechanisms of PUVA and NB-UVB in repigmentation are not thoroughly clarified. Our
      previous results showed that NB-UVB irradiation directly promotes melanocyte (MC)
      migration and stimulates MC proliferation via keratinocytes (KCs). OBJECTIVES: In
      the present study, we used NB-UVB as a reference for comparison to investigate
      the immediate effects of PUVA on MC proliferation and migration. METHODS:
      Cultured MCs and KCs were treated with PUVA or irradiated with NB-UVB. The direct
      impact of PUVA treatment on MCs was assessed in terms of its effect on MC
      proliferation and migration. The indirect effect of PUVA treatment and NB-UVB
      irradiation on MC proliferation via KCs was also investigated. The activities of
      matrix metalloproteinase (MMP)-2 and MMP-9, known for their influence on cell
      migration, were evaluated in the PUVA-treated MC and KC supernatants. The
      concentrations of MC mitogens/growth factors in the PUVA-treated KC supernatants
      were also determined. In addition, the serum levels of MC mitogens/growth factors
      in healthy controls, in patients with active vitiligo and in patients with
      repigmenting vitiligo after PUVA treatment were determined to elucidate the
      mechanisms of how PUVA induces vitiligo repigmentation in vivo. RESULTS: Our
      results demonstrated that PUVA treatment did not significantly stimulate the
      release of MC mitogens/growth factors from KCs. The migration of MCs was also not
      enhanced after PUVA treatment. The expression of MMP-2 activity in supernatants
      derived from PUVA-treated MCs was significantly increased as compared with the
      control group. However, neither MMP-2 nor MMP-9 activity in KC supernatants was
      stimulated by PUVA treatment. In contrast to NB-UVB, immediate effects of PUVA on
      MC proliferation and migration were not observed in this study. Sera from
      patients with repigmenting vitiligo after PUVA treatment contained higher levels
      of basic fibroblast growth factor, stem cell factor and hepatocyte growth factor
      as compared with healthy controls and patients with active vitiligo. CONCLUSIONS:
      Our results indicate that in addition to immune suppression, PUVA treatment
      creates a favourable milieu for promoting the growth of MCs in patients with
      vitiligo instead of directly stimulating the regrowth of MCs. Based on our
      results, we propose that in the active stage of vitiligo, PUVA treatment is the
      therapy of choice to slow down the destruction of MCs and to create a favourable
      environment for MCs to survive. In the stable stage of vitiligo, NB-UVB
      irradiation should be used to stimulate the proliferation and migration of MCs
      directly.

PMID- 17199579
TI  - A double-blind, randomized quantitative comparison of calcitriol ointment and
      calcipotriol ointment on epidermal cell populations, proliferation and
      differentiation.
AB  - BACKGROUND: Calcitriol and calcipotriol are widely used in the topical treatment
      of psoriasis. However, studies comparing both treatment modalities are scarce.
      Especially, there are almost no studies comparing the effects on epidermal cell
      populations in a quantitative manner. OBJECTIVES: The aim of this study was to
      quantitatively compare the effects of topical calcitriol and topical calcipotriol
      on clinical scores and epidermal subpopulations. PATIENTS AND METHODS: From five
      patients with stable plaque psoriasis, skin biopsies were taken from two
      symmetrical regions on the trunk or extremities before and after treatment with
      either calcitriol or calcipotriol. Frozen sections were labelled
      immunofluorescently using direct immunofluorescence for beta-1 integrin and the
      Zenon labelling technique for keratin (K) 6, K10 and K15. The digital photographs
      of the stained sections were quantitatively analysed and the results of both
      treatments were compared. RESULTS: The clinical SUM-score improved significantly
      for both the calcitriol- and the calcipotriol-treated lesions. In the
      calcipotriol-treated group the expression of K10 and K15 increased and the
      expression of K6 decreased significantly. No changes were seen for the marker
      beta-1 integrin. In the calcitriol-treated group none of the markers changed
      significantly. A tendency towards significance was seen for the changes in the
      expression of K6 and K15 in favour of calcipotriol. CONCLUSIONS: Both calcitriol
      and calcipotriol gave a significant improvement in clinical scores. However,
      treatment with calcipotriol resulted in a normalization of K6, K10 and K15,
      whereas treatment with calcitriol did not. Comparison of both treatments showed a
      tendency towards significance for the above-mentioned markers for calcipotriol
      only.

PMID- 17199580
TI  - Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice
      weekly and 50 mg once weekly in patients with psoriasis.
AB  - BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in
      the U.S.A., Canada and Europe for treating adult patients with chronic moderate
      to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy,
      safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are
      comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase
      3 study and a global phase 3 study were subsequently enrolled in an open-label
      extension study (extension study) where they all received etanercept at a dose of
      50 mg once weekly for an initial 12 weeks. Patients who had received at least 24
      weeks of etanercept 25 mg twice weekly in the global phase 3 study and were
      enrolled in the extension study (n = 265) were assessed for efficacy and safety
      at extension study baseline and after 12 weeks of etanercept 50 mg once weekly.
      Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the
      Dermatology Life Quality Index and the Physician's Global Assessment of
      psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were
      compared with PK profiles from another set of patients in the extension study.
      Comparison was made between a subset of patients receiving etanercept 25 mg twice
      weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept
      50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score
      was 5.77 at extension study baseline after treatment with etanercept 25 mg twice
      weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once
      weekly. Similar results were observed in other efficacy endpoints. Etanercept 50
      mg once weekly was generally well tolerated. No new safety findings were
      reported. PK profiles overlapped extensively between the two dosing regimens.
      CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles
      were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in
      patients who had received at least 24 weeks of etanercept 25 mg twice weekly
      prior to receiving etanercept 50 mg once weekly in the extension study.

PMID- 17199581
TI  - Nephro-urological complications of epidermolysis bullosa in paediatric patients.
AB  - A small but important proportion of patients with epidermolysis bullosa (EB) may
      develop significant renal and urological complications which can have a major
      impact on their morbidity and mortality. During the last 10 years, five of a
      large group of children with EB under our care, with either dystrophic or
      junctional types of disease, experienced major nephro-urological complications.
      Two patients with recessive dystrophic EB (REDB) developed macroscopic haematuria
      - one had renal failure and underwent a renal biopsy showing IgA nephropathy. A
      third patient with RDEB also developed renal failure and his biopsy demonstrated
      postinfectious glomerulonephritis/type III membranoproliferative
      (mesangiocapillary) glomerulonephritis. Both patients with renal failure
      underwent peritoneal dialysis. Two patients with junctional EB developed
      obstructive uropathies, which required bladder reconstruction and the fashioning
      of a Mitrofanoff channel in one.

PMID- 17199582
TI  - CD30+ large cell transformation of mycosis fungoides after psoralen plus
      ultraviolet A photochemotherapy.
AB  - Psoralen plus ultraviolet A (PUVA) photochemotherapy is widely used for the
      therapy of mycosis fungoides (MF). Clinical progression of MF is often associated
      with an increase in the size of tumour cells known as transformation. We report
      two patients with CD30+ large cell transformation that appeared after low-dose
      PUVA therapy for MF. Clinical data, histopathology, immunohistopathology and T
      cell receptor gene rearrangement were studied. Nodules consisted of atypical
      large cells that expressed CD30. Monoclonal rearrangement of T-cell receptors was
      observed in one case. Low-dose PUVA therapy may be associated with CD30+ large
      cell transformation in patients with MF.

PMID- 17199583
TI  - A failure of mucocutaneous lymphangiogenesis may underlie the clinical features
      of lipoid proteinosis.
AB  - Lipoid proteinosis (LiP) (OMIM 247100) is a rare autosomal recessive disease
      caused by loss of function mutations in the extracellular matrix protein 1 gene,
      ECM1, on chromosome 1q21. LiP is characterized clinically by hoarseness in early
      infancy, followed by waxy papules and plaques on the face and body along with pox
      like and acneiform scars. We studied a 20-year-old Japanese woman with LiP. She
      was born of consanguineous parents. Biopsy specimens obtained from a nodule on
      the elbow were used for histopathology, immunohistology and electron microscopy.
      Exons 6 and 7 of ECM1 were amplified by polymerase chain reaction (PCR) from
      genomic DNA from the proband, her parents, her brother and an unrelated person.
      PCR products were sequenced to detect the mutation. Histopathological examination
      revealed an irregular mass of calcium beneath deposits of a hyaline material in
      the dermis. Immunofluorescence double staining showed that the CD31-positive
      microvascular density was increased but that staining for the lymphatic-specific
      hyaluronan receptor LYVE-1 was drastically diminished in lesional compared with
      nonlesional skin of the patient and with normal skin. Electron microscopy
      revealed marked concentric reduplication of basal laminae not only around blood
      vessels but also around solitary dermal cells positive for Weibel-Palade bodies
      scattered in the hyaline material. Sequencing of the PCR products revealed a
      homozygous frameshift mutation, 507delT, in exon 6. This led to a premature stop
      codon 23 bp downstream. The results of immunopathological and ultrastructural
      characterization suggest that a failure of mucocutaneous lymphangiogenesis may
      underlie the clinical features of LiP. Identification of mutation 507delT in a
      Japanese patient with LiP further supports the thesis that this mutation
      represents a recurrent mutation in ECM1 in patients with LiP. To our knowledge,
      this case represents the first report of calcinosis cutis occurring in LiP.

PMID- 17199584
TI  - MSH6 mutation in Muir-Torre syndrome: could this be a rare finding?

PMID- 17199585
TI  - Painless periungual pyogenic granulomata associated with reverse transcriptase
      inhibitor therapy in a patient with human immunodeficiency virus infection.

PMID- 17199586
TI  - Melanomas in renal transplant recipients: the London experience, and invitation
      to participate in a European study.

PMID- 17199588
TI  - Clinical utility of an interferon-gamma-based assay for mycobacterial detection
      in papulonecrotic tuberculid.

PMID- 17199589
TI  - T cell/keratinocyte interactions in psoriasis: where is the trigger?

PMID- 17199590
TI  - Dapsone in the management of "insect bite-like reaction" in a patient with
      chronic lymphocytic leukaemia.

PMID- 17199591
TI  - Indurated nodules and plaques showing a dense plasma cell infiltrate as a
      cutaneous manifestation of Castleman's disease.

PMID- 17199592
TI  - Selenium intoxication: undesirable effect of a fasting cure.

PMID- 17199593
TI  - Differential clinical response to alefacept in combination with methotrexate in
      two patients with refractory palmar psoriasis.

PMID- 17199594
TI  - Cutaneous horn can be a clinical manifestation of underlying sebaceous carcinoma.

PMID- 17199596
TI  - A case of sporadic Bazex-Dupre-Christol syndrome presenting with scarring
      folliculitis of the scalp.

PMID- 17199595
TI  - Pseudosystemic sclerosis as a complication of recombinant human interleukin 2
      (aldesleukin) therapy.

PMID- 17199597
TI  - Moral and cost dilemma of a psoriasis patient.

PMID- 17199598
TI  - Reiter syndrome triggered by adalimumab (Humira) and leflunomide (Arava) in a
      patient with ankylosing spondylarthropathy and Crohn disease.

PMID- 17199599
TI  - Efalizumab-induced aseptic meningitis.

PMID- 17199600
TI  - Tacrolimus vs. clobetasol propionate in the treatment of facial cutaneous lupus
      erythematosus: a randomized, double-blind, bilateral comparison study.

PMID- 17199601
TI  - "Mechanic's hands": a misleading cutaneous sign of the antisynthetase syndrome.

PMID- 17199602
TI  - A successful therapeutic trial of rituximab in the treatment of a patient with
      recalcitrant, high-titre epidermolysis bullosa acquisita.

PMID- 17199603
TI  - Spotted and rippled reticulate hypermelanosis: a possible variant of Dowling
      Degos disease.

PMID- 17199604
TI  - Primary cutaneous follicular B-cell lymphoma arising at the site of radiotherapy
      for breast cancer.

PMID- 17199605
TI  - Additional dermoscopic presentation of haemosiderotic dermatofibroma.

PMID- 17199607
TI  - Forensic science does not start in the lab: the concept of diagnostic field
      tests.
AB  - An attempt to improve an analytical system can focus either on the actual
      processing or on the input. In forensic science, much emphasis has been placed on
      improving laboratory procedures, as though the input is already the best that can
      be obtained. Means of improving the basic input have gained much less attention.
      Yet, it must be agreed that even the best laboratory cannot gain from an item
      more than has been contained in it when it arrived from the field. The detection
      of latent materials at the crime scene by physical or chemical techniques and the
      diagnostic examination of material already discovered belong to the concept of
      diagnostic field tests. This group also includes "mapping" for the presence of
      certain materials, such as latent fingerprints through the distribution of amino
      acids on the surface. These tests are conducted outside the laboratory, without
      sophisticated instrumentation, at the crime scene, the suspect's home, or
      elsewhere. A significant advantage of the use of diagnostic field tests is the
      ability to deal with "dissipating evidence" such as gunshot residue or explosive
      traces on the hands of suspects. If time is lost, there is a risk of losing such
      evidence, which is liable to deteriorate rapidly. In my presentation, I will
      discuss older and some newly developed forensic field tests, with specific
      emphasis on the Israeli experience.

PMID- 17199608
TI  - Differences among species in compact bone tissue microstructure of mammalian
      skeleton: use of a discriminant function analysis for species identification.
AB  - In order to develop an identification key for distinguishing between several
      mammalian species, bone structure of their compact bone tissue was analyzed using
      qualitative and quantitative characteristics. Ninety femora of adult male humans,
      pigs, cows, sheep, rabbits, and rats were studied. The average area, perimeter,
      minimum, and maximum diameter of 1863 Haversian canals and 1863 secondary osteons
      were measured using a digital image device. The observed data were first used to
      evaluate inter- and intraspecies diversity. After that, we applied a discriminant
      function analysis for differentiation of the species by these variables.
      Classification functions for investigated species give cross-validated correct
      classification rates for 76.17% of cases. This percentage value can be increased
      by integrating conclusions from the qualitative analysis.

PMID- 17199609
TI  - Ontogeny of femur subtrochanteric shape in Native Americans and American Blacks
      and Whites.
AB  - Femur subtrochanteric size and shape can be used to differentiate between adult
      Native Americans and American Blacks and Whites, but little is known about when
      shape differences are established during growth and development. Ontological
      changes in subtrochanteric shape were examined using 74 Native American and 61
      American Black/White subadult femora. At birth, the proximal femur diaphysis is
      relatively circular in both groups. Between birth and 5 years, the diaphysis
      becomes more mediolaterally broad, especially in Native Americans, due to
      differential growth between the mediolateral and anteroposterior planes. This
      change may be due to biomechanical stresses associated with developing a mature
      gait pattern. After the age of 5, growth occurs more equally in the two planes
      and shape does not change significantly. The adult shape of the proximal femur is
      established by c. 5 years of age and can be used to discriminate between Native
      American and American Black/White femora in older subadults.

PMID- 17199611
TI  - Computation of likelihood ratios in fingerprint identification for configurations
      of three minutiae.
AB  - Recent challenges to fingerprint evidence have brought forward the need for peer
      reviewed scientific publications to support the evidential value assessment of
      fingerprint. This paper proposes some research directions to gather statistical
      knowledge of the within-source and between-sources variability of configurations
      of three minutiae on fingermarks and fingerprints. This paper proposes the use of
      the likelihood ratio (LR) approach to assess the value of fingerprint evidence.
      The model explores the statistical contribution of configurations of three
      minutiae using Tippett plots and related measures to assess the quality of the
      system. Features vectors used for statistical analysis have been obtained
      following a preprocessing step based on Gabor filtering and image processing to
      extract minutia position, type, and direction. Spatial relationships have been
      coded using Delaunay triangulation. The metric, used to assess similarity between
      two feature vectors is based on an Euclidean distance measure. The within-source
      variability has been estimated using a sample of 216 fingerprints from four
      fingers (two donors). Between-sources variability takes advantage of a database
      of 818 ulnar loops from randomly selected males. The results show that the data
      driven approach adopted here is robust. The magnitude of LRs obtained under the
      prosecution and defense propositions stresses upon the major evidential
      contribution that small portions of fingermark, containing three minutiae, can
      provide regardless of its position on the general pattern.

PMID- 17199610
TI  - Interoperator test for anatomical annotation of earprints.
AB  - As part of the Forensic Ear Identification (FearID) research project, which aims
      to obtain estimators for the strength of evidence of earmarks found on crime
      scenes, a large database of earprints (over 1200 donors) has been collected.
      Starting from a knowledge-based approach where experts add anatomical annotations
      of minutiae and landmarks present in prints, comparison of pairs of prints is
      done using the method of Vector Template Matching (VTM). As the annotation
      process is subjective, a validation experiment was performed to study its
      stability. Comparing prints on the basis of VTM, it appears that there are
      interoperator effects, individual operators yielding significantly more
      consistent results when annotating prints than different operators. The operators
      being well trained and educated, the observed variation on both clicking
      frequency and choice of annotation points suggests that implementation of the
      above is not the best way to go about objectifying earprint comparison. Processes
      like the above are relevant for any forensic science dealing with identification
      (e.g., of glass, tool marks, fibers, faces, fingers, handwriting, speakers) where
      manual (nonautomated) processes play a role. In these cases, results may be
      operator dependent and the dependencies need to be studied.

PMID- 17199612
TI  - Amino acid alanine reactivity with the fingerprint reagent ninhydrin. A detailed
      ab initio computational study.
AB  - Ninhydrin is one of the most widely used reagents for chemical development of
      fingerprints on porous surfaces. The detection is based on the reaction of
      ninhydrin with a monoacidic component of the fingerprint to form an intensively
      colored compound named Ruhemann's Purple. A computational study of the mechanisms
      and reaction energetics of the formation of Ruhemann's Purple from ninhydrin and
      alanine is presented. Such a study is significant from a forensic science point
      of view because of the strong interest in the forensic chemistry and law
      enforcement communities in developing alternatives to the current generation of
      ninhydrin like chemicals for the detection and development of latent
      fingerprints. Information about the mechanism of reaction between ninhydrin and
      amino acids can ultimately help to design compounds with stronger chromo
      fluorogenic properties in aid of detecting fingerprints at crime scenes. The
      three most accepted mechanisms of formation have been considered using ab initio
      quantum mechanical calculations. At relatively high temperature ( approximately
      100 degrees C) all three mechanisms are energetically feasible. However since it
      is recommended that forensic analyses be performed at room temperature, a revised
      mechanism is proposed for the formation of Ruhemann's Purple under this
      condition.

PMID- 17199613
TI  - Bank security dye packs: synthesis, isolation, and characterization of
      chlorinated products of bleached 1-(methylamino)anthraquinone.
AB  - Banknote evidence is often submitted after a suspect has attempted to disguise or
      remove red dye stain that has been released because of an anti-theft device that
      activates after banknotes have been unlawfully removed from bank premises. Three
      chlorinated compounds have been synthesized as forensic chemical standards to
      indicate bank security dye bleaching as a suspect's intentional method for
      masking a robbery involving dye pack release on banknotes. A novel, facile
      synthetic method to provide three chlorinated derivatives of 1
      (methylamino)anthraquinone (MAAQ) is presented. The synthetic route involved
      Ultra Clorox bleach as the chlorine source, iron chloride as the catalyst, and
      MAAQ as the starting material and resulted in a three-component product mixture.
      Two mono-chlorinated isomers (2-chloro-1-(methylamino)anthraquinone and 4-chloro
      1-(methylamino)anthraquinone) and one di-chlorinated compound (2,4-dichloro-1
      (methylamino)anthraquinone) of the MAAQ parent molecule were detected by gas
      chromatography mass spectrometry (GC-MS), and subsequently isolated by liquid
      chromatography (LC) with postcolumn fraction collection. Although GC-MS is
      sensitive enough to detect all of the chlorinated products, it is not definitive
      enough to identify the structural isomers. Liquid-state nuclear magnetic
      resonance (NMR) spectroscopy was utilized to elucidate structurally the ortho-
      and para-mono-chlorinated isomers once enough material was properly isolated. A
      reaction mechanism involving iron is proposed to explain the presence of
      chlorinated MAAQ species on stolen banknotes after attempted bleaching.

PMID- 17199614
TI  - Least-square deconvolution: a framework for interpreting short tandem repeat
      mixtures.
AB  - Interpreting mixture short tandem repeat DNA data is often a laborious process,
      involving trying different genotype combinations mixed at assumed DNA mass
      proportions, and assessing whether the resultant is supported well by the
      relative peak-height information of the mixture sample. If a clear pattern of
      major-minor alleles is apparent, it is feasible to identify the major alleles of
      each locus and form a composite genotype profile for the major contributor. When
      alleles are shared between the two contributors, and/or heterozygous peak
      imbalance is present, it becomes complex and difficult to deduce the profile of
      the minor contributor. The manual trial and error procedures performed by an
      analyst in the attempt to resolve mixture samples have been formalized in the
      least-square deconvolution (LSD) framework reported here for two-person mixtures,
      with the allele peak height (or area) information as its only input. LSD operates
      on the peak-data information of each locus separately, independent of all other
      loci, and finds the best-fit DNA mass proportions and calculates error residual
      for each possible genotype combination. The LSD mathematical result for all loci
      is then to be reviewed by a DNA analyst, who will apply a set of heuristic
      interpretation guidelines in an attempt to form a composite DNA profile for each
      of the two contributors. Both simulated and forensic peak-height data were used
      to support this approach. A set of heuristic guidelines is to be used in forming
      a composite profile for each of the mixture contributors in analyzing the
      mathematical results of LSD. The heuristic rules involve the checking of
      consistency of the best-fit mass proportion ratios for the top-ranked genotype
      combination case among all four- and three-allele loci, and involve assessing the
      degree of fit of the top-ranked case relative to the fit of the second-ranked
      case. A different set of guidelines is used in reviewing and analyzing the LSD
      mathematical results for two-allele loci. Resolution of two-allele loci is
      performed with less confidence than for four- and three-allele loci. This paper
      gives a detailed description of the theory of the LSD methodology, discusses its
      limitations, and the heuristic guidelines in analyzing the LSD mathematical
      results. A 13-loci sample case study is included. The use of the interpretation
      guidelines in forming composite profiles for each of the two contributors is
      illustrated. Application of LSD in this case produced correct resolutions at all
      loci. Information on obtaining access to the LSD software is also given in the
      paper.

PMID- 17199616
TI  - Microbial metagenome profiling using amplicon length heterogeneity-polymerase
      chain reaction proves more effective than elemental analysis in discriminating
      soil specimens.
AB  - The combination of soil's ubiquity and its intrinsic abiotic and biotic
      information can contribute greatly to the forensic field. Although there are
      physical and chemical characterization methods of soil comparison for forensic
      purposes, these require a level of expertise not always encountered in crime
      laboratories. We hypothesized that soil microbial community profiling could be
      used to discriminate between soil types by providing biological fingerprints that
      confer uniqueness. Three of the six Miami-Dade soil types were randomly selected
      and sampled. We compared the microbial metagenome profiles generated using
      amplicon length heterogeneity-polymerase chain reaction analysis of the 16S rRNA
      genes with inductively coupled plasma optical emission spectroscopy analysis of
      13 elements (Al, B, Ca, Cu, Fe, K, Mg, Mn, Na, P, S, Si, and Zn) that are
      commonly encountered in soils. Bray-Curtis similarity index and analysis of
      similarity were performed on all data to establish differences within sites,
      among sites, and across two seasons. These data matrices were used to group
      samples that shared similar community patterns using nonmetric multidimensional
      scaling analysis. We concluded that while chemical characterization could provide
      some differentiation between soils, microbial metagenome profiling was better
      able to discriminate between the soil types and had a high degree of
      reproducibility, therefore proving to be a potential tool for forensic soil
      comparisons.

PMID- 17199615
TI  - Testing and evaluation of 43 "noncore" Y chromosome markers for forensic casework
      applications.
AB  - A developmental validation study was performed on three Y-STR multiplex systems,
      Multiplex III (MPIII), Multiplex IV (MPIV), and Multiplex V (MPV), to ascertain
      their potential applicability to forensic casework. MPIII contains eight Y-STRs,
      including DYS426, DYS435, DYS436, DYS441, DYS442, DYS446, DYS462, and Y-GATA-A10,
      and one InDel, YAP (DYS287). MPIV contains 21 Y-STR loci, including DYS443,
      DYS444, DYS445, DYS447, DYS448, DYS449, DYS452, DYS453, DYS454, DYS455, DYS456,
      DYS458, DYS463, DYS464, DYS468, DYS484, DYS522, DYS527, DYS531 DYS557, and
      DYS588. MPV contains 13 Y-STR loci, including DYS459, DYS476, DYS488, DYS513,
      DYS549, DYS561, DYS570, DYS575, DYS576, DYS590, DYS594, DYS598, and DYS607. Full
      genetic profiles were consistently obtained for all three multiplexes with 25-50
      pg of male DNA. No significant amplification was observed with 1 mug of female
      DNA. Each multiplex permitted the determination of the number of male donors in
      male:male DNA admixtures. Species specificity studies demonstrated some cross
      reactivity with some primate samples. Environmentally compromised blood samples
      produced full or partial profiles after exposure to various conditions for up to
      1 year. Full profiles were recovered from simulated casework specimens including
      cigarette butts and postcoital cervicovaginal swabs. Population data were
      collected to determine individual loci gene diversity and multiplex
      discriminatory capacity.

PMID- 17199617
TI  - A mechanistic model for the superglue fuming of latent fingerprints.
AB  - The use of superglue vapors to detect latent fingerprints, known as superglue
      fuming, is a chemical process that has not been fully described. The role of the
      fingerprint material in the process, leading to formation of methyl cyanoacrylate
      polymer at the site of the fingerprint, remains to be established. Films of
      liquid alkanes respond similarly to actual fingerprints in the fuming experiment.
      Their responses depended on the hydrocarbon used, viscosity, and film thickness.
      Aspects such as film thickness appear to be relevant for actual fingerprints as
      well. A model was proposed in light of these observations. The model compares the
      process with gas chromatography, in which molecules partition between the gas
      phase and a stationary phase. Aspects such as accumulation of superglue monomers
      by partitioning into a thin film (or wax) are consistent with the preferential
      response of fingerprints on surfaces relative to the background.

PMID- 17199618
TI  - Development of a GC-MS method for the simultaneous analysis of latent fingerprint
      components.
AB  - Latent fingerprint residue is a complex mixture of organic and inorganic
      compounds. A full understanding of the composition of this mixture and how it
      changes after deposition is lacking. Three solvent systems were compared for the
      simultaneous extraction and derivatization with ethyl chloroformate of selected
      amino and fatty acids from a nonporous substrate (Mylar for subsequent analysis
      by gas chromatography-mass spectrometry. A solvent system comprised of sodium
      hydroxide, ethanol, and pyridine was found to be the most effective. This method
      was applied to the analysis of latent fingerprint residue deposited on Mylar and
      preliminary data are presented. Twelve amino acids (e.g., serine, glycine, and
      aspartic acid) and 10 fatty acids (e.g., tetradecanoic, hexadecanoic, and
      octadecanoic acids) were identified. The potential application of this method to
      further the understanding of latent fingerprint chemistry has been demonstrated.

PMID- 17199619
TI  - Analytical methods used for the discrimination of substances suspected to be bar
      soap: a preliminary study.
AB  - The submission to forensic laboratories of unknown specimens suspected of being
      biological or chemical warfare agents has increased tremendously with the threat
      of terrorism. Oftentimes, a threatening correspondence that contains hoax
      materials is intended to make the recipient(s) believe they have been exposed to
      a toxin. In some cases, the perpetrator can use standard household products, such
      as detergents and soaps. Once these materials are received, they become forensic
      evidence and may be analyzed for identification and/or comparison with known
      seized material from a suspect(s). Two separate studies were conducted using
      different analytical protocols for bar soaps. In the first set, the forensic
      laboratory at the United States Secret Service conducted tests on 68 bars of soap
      using solid-phase microextraction and gas chromatography coupled with mass
      spectrometry. The 68 different soaps displayed unique total ion chromatogram
      profiles. Energy-dispersive X-ray analysis in conjunction with scanning electron
      microscopy was also used to characterize 46 of the 68 soaps as a preliminary
      study. In a second set of studies, as part of a homicide investigation, the
      laboratory at the California Department of Justice, Riverside, conducted
      examinations on 13 bars of soap by utilizing Fourier transform-infrared
      spectroscopy. The case study demonstrated that it is possible to distinguish some
      bar soaps using infrared analysis. Furthermore, the bar soaps could be
      distinguished from typical laundry detergents using this technique.

PMID- 17199620
TI  - The utility of whole genome amplification for typing compromised forensic
      samples.
AB  - Biological evidence has become invaluable in the crime laboratory; however, it
      may exist in limited quantity and/or quality. Given this, the ability to amplify
      total DNA obtained from evidence, in an unbiased manner, would be highly
      advantageous. Methods for whole genome amplification (WGA) have the potential to
      fulfill this role, resulting in a virtually unlimited supply of DNA. In the
      research presented, two WGA methods, improved primer extension preamplification
      and multiple displacement amplification (MDA), were tested using commercial kits.
      Control DNA, artificially degraded DNA, and DNA from fresh blood, aged blood,
      hair shafts, and aged bones underwent WGA, followed by short tandem repeat and
      mitochondrial DNA analysis. The methods did amplify DNA, but performed poorly on
      forensically relevant samples; the maximum amplicon size was reduced, and MDA
      often resulted in extraneous bands following polymerase chain reaction. Taken
      together, WGA appears to be of limited forensic utility unless the samples are of
      a very high quality.

PMID- 17199621
TI  - Two items of evidence, no putative source: an inference problem in forensic
      intelligence.
AB  - Intelligence analysts commonly associate cases on the basis of similarities found
      in compared characteristics of scientific evidence. The present paper studies
      some of the inferential difficulties associated with such operations. An analysis
      is proposed that breaks down the reasoning process into inference to common
      source, and inference to case linkage. The former requires an approach to the
      difficulty associated with evaluating the similarities of items of evidence from
      different cases with no putative source being available. The latter requires
      consideration to be given to the relevance of evidence. Throughout the paper,
      probability theory is used to describe the nature of the proposed inferences.
      Graphical models are also introduced with the aim of providing further insight
      into the dependence and independence relationships assumed to hold among the
      various propositions considered. Notions from decision theory are used to discuss
      ways in which intelligence analysts may assist investigators in deciding whether
      or not cases should be considered as linked.

PMID- 17199622
TI  - Serial murder by healthcare professionals.
AB  - The prosecution of Charles Cullen, a nurse who killed at least 40 patients over a
      16-year period, highlights the need to better understand the phenomenon of serial
      murder by healthcare professionals. The authors conducted a LexisNexis search
      which yielded 90 criminal prosecutions of healthcare providers that met inclusion
      criteria for serial murder of patients. In addition we reviewed epidemiologic
      studies, toxicology evidence, and court transcripts, to provide data on
      healthcare professionals who have been prosecuted between 1970 and 2006. Fifty
      four of the 90 have been convicted; 45 for serial murder, four for attempted
      murder, and five pled guilty to lesser charges. Twenty-four more have been
      indicted and are either awaiting trial or the outcome has not been published. The
      other 12 prosecutions had a variety of legal outcomes. Injection was the main
      method used by healthcare killers followed by suffocation, poisoning, and
      tampering with equipment. Prosecutions were reported from 20 countries with 40%
      taking place in the United States. Nursing personnel comprised 86% of the
      healthcare providers prosecuted; physicians 12%, and 2% were allied health
      professionals. The number of patient deaths that resulted in a murder conviction
      is 317 and the number of suspicious patient deaths attributed to the 54 convicted
      caregivers is 2113. These numbers are disturbing and demand that systemic changes
      in tracking adverse patient incidents associated with presence of a specific
      healthcare provider be implemented. Hiring practices must shift away from
      preventing wrongful discharge or denial of employment lawsuits to protecting
      patients from employees who kill.

PMID- 17199623
TI  - Digital analysis of experimental human bitemarks: application of two new methods.
AB  - Bitemark determination in forensic odontology is commonly performed by comparing
      the morphology of the dentition of the suspect with life-sized photographs of
      injury on the victim's skin using transparent overlays or computers. The purpose
      of this study is to investigate the suitability of two new different methods for
      identification of bitemarks by digital analysis. A sample of 50 volunteers was
      asked to make experimental bitemarks on the arms of each other. Stone study casts
      were prepared from upper and lower dental arches of each volunteer. The bitemarks
      and the study casts were photographed; the photos were entered into the computer
      and Adobe Photoshop software program was applied to analyze the results. Two
      methods (2D polyline and Painting) of identification were used. In the 2D
      polyline method, fixed points were chosen on the tips of the canines and a
      straight line was drawn between the two fixed points in the arch (intercanine
      line). Straight lines passing between the incisal edges of the incisors were
      drawn vertically on the intercanine line; the lines and angles created were
      calculated. In the painting method, identification was based on canine-to-canine
      distance, tooth width and the thickness, and rotational value of each tooth. The
      results showed that both methods were applicable. However, the 2D polyline method
      was more convenient to use and gave prompt computer-read results, whereas the
      painting method depended on the visual reading of the operator.

PMID- 17199624
TI  - Sex determination using nonmetric characteristics of the mandible in Koreans.
AB  - The mandible is the largest and hardest facial bone and retains its shape better
      than other bones in the forensic and physical anthropologic field. The mandible
      can be used to distinguish among ethnic groups and between sexes. We examined the
      morphological characteristics of the mandibles of 102 Koreans of either sex. Of
      13 nonmetric items of the mandible, the characteristic that best allowed the
      sexes to be distinguished was the contour of the lower border of the mandible:
      rocker-shaped mandibles predominated in males (68.1%), whereas most females
      (84.6%) exhibited a straight mandible. In addition, the mental region was shaped
      differently between the sexes: the shape of the chin in most males was generally
      bilobate or square (91.7%), whereas the chin in females was either square (45.5%)
      or pointed (54.5%). In this study, the positive predict values of male and female
      were 92.5% and 73.7%, respectively. Therefore, the nonmetric method used to
      analyze the mandible in this study can be used for sex discrimination.

PMID- 17199625
TI  - Accidental deaths caused by electricity in Sweden, 1975-2000.
AB  - This study analyzes accidental fatalities caused by electricity--at work and
      during leisure time--to evaluate risk factors, the role of alcohol, and to
      identify possible preventive strategies. In Sweden, data on fatalities by
      electrocution from 1975 through 2000 were collected from the National Cause-of
      Death Register. Additional cases were found in the archives of The Swedish
      National Electrical Safety Board. Suicides and deaths by lightning were excluded.
      Two hundred and eighty-five deaths were found, including occupational (n=132),
      leisure time (n=151), and unknown (n=2). Most deaths were caused by aerial power
      lines, and the most common place for an electrical injury was a railway area or
      residential property. Postmortem blood from 20% (n=47) of the tested cases was
      found positive for alcohol, and these persons were killed mainly during leisure
      time. During the study period, the overall incidence of electricity-related
      fatalities has decreased, in spite of increased use of electricity. This
      indicates that safety improvements have been successful.

PMID- 17199626
TI  - Alpha-amylase kinetic test in bodily single and mixed stains.
AB  - Recently, in Italy, a murder and a putative sexual violence was accomplished on a
      child. A bodily fluids mixture on the child's underwear between the victim
      (female) and the suspect (male) was ascertained by short tandem repeat (STR) DNA
      typing and, due to the absence of seminal fluid, saliva from the suspect and
      urine from the child was hypothesized. In order to investigate the possibility of
      specifically and rapidly detecting saliva stains both alone and mixed with other
      bodily fluids, we used a quantitative spectrophotometric technique, named Amylase
      test, for the detection of alpha-amylases. We determined alpha-amylase activity
      and reaction kinetic curves in several samples collected from the child's
      underwear. In order to confirm our intuition, we first tested saliva,
      perspiration, and urine, singularly and in mixtures; second, several forensic
      stains including saliva, perspiration, urine stains, saliva/perspiration, and
      saliva/urine mixture stains were tested. Evaluating alpha-amylase activity values
      and time-course curves' behavior of alpha-amylase reactions we were able to
      recognize successfully, in all cases, the presence of saliva and to distinguish
      it specifically from other bodily fluids containing alpha-amylase. A further
      confirmation of our result was provided by STR DNA typing on several areas of the
      underwear: a clear correlation between alpha-amylases activity and male DNA was
      detected on all the samples evaluated.

PMID- 17199627
TI  - Visual attention and expertise for forensic signature analysis.
AB  - Eye tracking was used to measure visual attention of nine forensic document
      examiners (FDEs) and 12 control subjects on a blind signature comparison trial.
      Subjects evaluated 32 questioned signatures (16 genuine, eight disguised, and
      eight forged) which were compared, on screen, with four known signatures of the
      specimen provider while their eye movements, response times, and opinions were
      recorded. FDEs' opinions were significantly more accurate than controls,
      providing further evidence of FDE expertise. Both control and FDE subjects looked
      at signature features in a very similar way and the difference in the accuracy of
      their opinions can be accounted for by different cognitive processing of the
      visual information that they extract from the images. In a separate experiment
      the FDEs re-examined a reordered set of the same 32 questioned signatures. In
      this phase each signature was presented for only 100 msec to test if eye
      movements are relevant in forming opinions; performance significantly dropped,
      but not to chance levels indicating that the examination process comprises a
      combination of both global and local feature extraction strategies.

PMID- 17199628
TI  - Commentary on: Datwyler SL, Weiblen GD. Weiblen. Genetic variation in hemp and
      marijuana (Cannabis sativa L.) according to amplified fragment length
      polymorphisms. J Forensic Sci 2006;51:371-5.

PMID- 17199631
TI  - Genetic analysis of 15 STR loci of Chinese Ewenki ethnic population.

PMID- 17199632
TI  - Minnesota population data on 15 STR loci using the Identifiler kit.

PMID- 17199633
TI  - Genetic data of 16 Y-chromosomal short tandem repeat loci in Africans from South
      Africa.

PMID- 17199634
TI  - Genetic analysis for Y chromosome short tandem repeat haplotypes of Chinese Han
      population residing in the Ningxia province of China.

PMID- 17199635
TI  - Analysis of short tandem repeat polymorphisms in the southwest Chinese
      population.

PMID- 17199636
TI  - Distribution of D6S1041, D10S1426, and GATA168F06 alleles in a Chinese population
      sample.

PMID- 17199637
TI  - Y-STR concordance study between Y-Plex5, Y-Plex6, Y-Plex12, PowerplexY, Y-Filer,
      MPI, and MPII.

PMID- 17199638
TI  - Population genetics of five Y-chromosomal short tandem repeat haplotypes in the
      Chinese Han population.

PMID- 17199639
TI  - Y chromosomal short tandem repeat haplotypes in the Japanese population.

PMID- 17199640
TI  - Haplotype diversity at 20 Y-chromosome microsatellites in an Indo-Caucasian
      population of Bengal, India.

PMID- 17199649
TI  - Lactic acid chemical peels as a new therapeutic modality in melasma in comparison
      to Jessner's solution chemical peels.
AB  - BACKGROUND: Many chemicals have been used in the skin peeling for melasma such as
      Jessner's solution and glycolic acid. Lactic acid is an alpha-hydroxy acid that
      has not been used before in chemical peeling of melasma. OBJECTIVE: The purpose
      of the present work was to evaluate the efficacy and safety of lactic acid in
      chemical peeling of melasma in comparison to Jessner's solution chemical peels.
      METHODS: This study was conducted at the Department of Dermatology and
      Venereology, Baghdad Hospital, in the period between April 2001 and August 2002.
      Thirty patients with melasma were included in this study. They were mostly of
      skin type IV according to Fitzpatrick's classification, 26 (86.67%) were women,
      and 4 (13.33%) were men, with an age range from 18 and 50 years (mean+/-SD,
      33.53+/-6.96 years). Full clinical examination was done to all patients including
      Wood's light. The severity of melasma was assessed by MASI (Melasma Area Severity
      Index). Pure lactic acid full strength (92%, pH 3.5) was used as a new peeling
      agent on the left side of the face while Jessner's solution was applied to the
      right side of the face. The chemical peeling sessions were done every 3 weeks
      until the desired response was achieved. Follow-up was carried out for 6 months
      after the last session. RESULTS: Six patients were defaulted from the study after
      the first session for unknown reasons. Twenty-four patients completed the study.
      Twenty (83.33%) were women and four were men (16.67%). Wood's light examination
      showed increased contrast in all patients of mostly epidermal melasma. The number
      of sessions ranged from 2 to 5. All patients showed marked improvement as
      calculated by MASI score before and after treatment, and the response was highly
      statistically significant. No side effect was recorded in all treated patients.
      CONCLUSION: Lactic acid was found to be an effective and safe peeling agent in
      the treatment of melasma, and it was as effective as Jessner's solution.

PMID- 17199650
TI  - Enhancement of viability of fat grafts in nude mice by endothelial progenitor
      cells.
AB  - BACKGROUND: A recent discovery showed that endothelial progenitor cells (EPCs)
      could augment collateral vessel growth to ischemic tissues. OBJECTIVE: The
      objective was to demonstrate the effects of EPCs on the vasculogenesis and
      survival of free transplanted fat tissues in nude mice. METHODS: EPCs from human
      donors were cultured in vitro for 7 days. Human fat tissues were injected
      subcutaneously into the scalps of 20 6-week-old nude male mice. EPCs stained with
      CM-DiI were mixed with the transplanted fat tissues and injected into the mice.
      EBM-2 medium was used as control group. The animals were euthanized 15 weeks
      after the procedure. Graft volume were measured, and histologic evaluation was
      performed. The central part of fat tissues was histologically evaluated 15 weeks
      after the fat injection. RESULTS: The survival volume of the experimental group
      was significantly greater than that of the control group (p< .05). Less cyst
      formation and fibrosis was obtained in the experimental group. Histologic
      evaluation of the central part of fat tissues 15 weeks after the fat injection
      showed that capillary densities increased markedly in the experimental group
      mice. CONCLUSION: The results indicate that EPCs have the ability to enhance the
      survival and the quality of the transplanted fat tissues.

PMID- 17199652
TI  - Incompetent great saphenous veins treated with endovenous 1,320-nm laser: results
      for 71 legs and morphologic evolvement study.
AB  - BACKGROUND: Endovenous lasers with various wavelengths have been utilized with
      good outcomes in treating leg varicose veins. The natural history and evolution
      of treated veins after endovenous procedures, however, have seldom been
      addressed. OBJECTIVE: This study determines the efficacy vein ablation and serial
      venous morphologic evolution of incompetent great saphenous veins (GSVs) after
      endovenous 1,320-nm laser treatment. METHODS: Fifty patients with symptomatic
      varicose veins secondary to GSV insufficiency treated with 1,320-nm endovenous
      laser ablation were enrolled. The treated varicose veins in each limb were mapped
      and sized before laser treatment. Vein wall diameters were measured with duplex
      ultrasound at follow-up visits. RESULTS: Seventy-one limbs in 50 patients were
      enrolled. During the mean 13.1-month follow-up, closure of GSVs was observed in
      94% of limbs (67/71). Vein diameters at 3 cm below saphenofemoral junction level
      were reduced to 81% at 2 days, 75% at 1 month, 48% at 3 months, and 39% at 5
      months. Average mean duration for treated GSVs to narrow as fibrotic cords
      (internal diameter,<2.5 mm) was 5.8 months. CONCLUSION: The endovenous 1,320-nm
      laser ablation procedures have excellent efficacy in treating incompetent GSVs.
      This excellent shrinkage behavior may be the basis for nice long-term results of
      patients treated with 1,320-nm Cooltouch endovenous laser.

PMID- 17199651
TI  - Dose- and time-dependent liquid sclerosant effects on endothelial cell death.
AB  - BACKGROUND: Intravenous sclerotherapy solutions can induce endothelial cell
      death. OBJECTIVE: The objective was to determine the relationship between
      sclerosant concentration and minimum contact time required for in endothelial
      cell death. METHODS: Cultured bovine aortic endothelial cells were exposed to a
      broad range of concentrations of two liquid sclerosants, polidocanol and sodium
      tetradecyl sulfate. Fluorescence microscopy was used to study cells using dyes
      specifically indicating changes in intracellular calcium levels, nitric oxide
      production, and loss of cell membrane integrity after sclerosant exposure.
      Fluorescence intensity measurements were used to identify the timing of cell
      death. RESULTS: Calcium signaling and nitric oxide pathways were activated by the
      administration of the sclerosants and were followed by cell death. The time to
      the activation and the cell death was dependent on the concentration of
      sclerosants. At 0.3% polidocanol or 0.1% sodium tetradecyl sulfate, cell death
      occurred within 15 minutes. At less than 0.003% polidocanol and at 0.005% sodium
      tetradecyl sulfate, cells remained alive after 60 minutes. CONCLUSION: Both
      sclerosants rapidly led to cell death at sufficiently high concentrations. At low
      sclerosant concentrations, cell viability was maintained beyond the recording
      time of the experiment. The timing of endothelial cell death is predictable based
      on sclerosant concentration during exposure.

PMID- 17199653
TI  - Postacne scarring: a qualitative global scarring grading system.
AB  - BACKGROUND: There is no global qualitative grading system for assessing the
      disease load and global severity of disease in a patient with postacne scarring.
      OBJECTIVE: The purpose of this article is to provide a simple qualitative grading
      system that would allow better communication between practitioners of a patient's
      global disease severity and the most appropriate corresponding therapy for that
      degree of acne scarring. METHODS: Four grades of postacne scarring are described,
      and appropriate therapeutic interventions are presented for each. Grade
      assignment is made by lesion morphologies and disease load as indicated by
      patient perception of severity (i.e., whether or not an individual can easily
      disguise his or her disease at social distances). RESULTS: A simple qualitative
      global acne scarring grading system is presented. LIMITATIONS: The determination
      of disease load in terms of patient perception of severity is intrinsically
      imperfect due to varying subjectivity among individuals. CONCLUSION: A global
      acne scarring grading system is presented that is simple to use and may optimize
      therapeutic intervention. This system would also allow investigators, educators,
      and proceduralists to compare their cases more accurately and to have a more
      objective discussion of the efficacy of operative interventions or therapies.

PMID- 17199654
TI  - Mesotherapy for facial skin rejuvenation: a clinical, histologic, and electron
      microscopic evaluation.
AB  - BACKGROUND AND OBJECTIVE: Mesotherapy, as broadly defined, represents a variety
      of minimally invasive techniques in which medications are directly injected into
      the skin and underlying tissue in order to improve musculoskeletal, neurologic,
      and cosmetic conditions. There are few clinical studies evaluating the efficacy
      and safety of mesotherapy in any form. This study evaluates the histologic and
      clinical changes associated with one of the simplest formulations of mesotheraphy
      commonly used for skin rejuvenation. STUDY DESIGN: Ten subjects underwent four
      sessions of mesotherapy involving multiple injections of a multivitamin and
      hyaluronic acid solution. Treatment was conducted at 4 monthly intervals. All
      subjects had pre- and post-treatment photographs and skin biopsies. Skin biopsies
      were evaluated with routine histology, mucin and elastin stains, and electron
      microscopy. Patient surveys were also evaluated. RESULTS: Evaluation of
      photographs at 0, 3, and 6 months revealed no significant clinical differences.
      Light microscopic examination of pre- and posttreatment specimens showed no
      significant changes. Electron microscopic analysis of collagen fibers
      measurements did show smaller diameter fibres posttreatment. CONCLUSION: No
      significant clinical or histologic changes were observed after multivitamin
      mesotherapy for skin rejuvenation. Multivitamin and hyaluronic acid solution
      facial mesotherapy does not appear to provide any significant benefit.

PMID- 17199655
TI  - Nonmelanoma skin cancer: is the incidence really increasing among patients
      younger than 40? A reexamination using 25 years of U.S. outpatient data.
AB  - OBJECTIVE: An increasing incidence of basal cell carcinomas and squamous cell
      carcinomas in patients younger than 40 years old diagnosed during years 1973 to
      2003 was found in a recent population-based study in Olmsted County, Minnesota.
      We performed additional analyses using nationally representative patient samples
      to confirm these trends. STUDY DESIGN: We analyzed a cross-sectional survey data
      on outpatient diagnoses, the National Ambulatory Medical Care Survey data from
      1979 to 2003, for melanoma skin cancer. RESULTS: A total of 4,100 office visits
      for nonmelanoma skin cancers were recorded, including 230 in patients younger
      than 40. Multivariate analysis indicated no significant increase in the number of
      office visits related to nonmelanoma skin cancer in younger patients [odds ratio
      (OR), 2.77; 95% CI, 0.75-10.26]. The mean age of office visits for nonmelanoma
      skin cancer did not change significantly. The ages of the office visit patients
      were 64.7 years and 69.02 years in the years 1979 and 2003, respectively.
      CONCLUSIONS: Based on a representative sample of outpatient visit diagnoses,
      visits are not increasing for nonmelanoma skin cancer among patients 40 years and
      younger in the United States, albeit direct measurement of tumor incidence was
      not possible with this database.

PMID- 17199657
TI  - Derm Access: a new triage system to rapidly identify suspicious skin lesions.
AB  - BACKGROUND: Many screening programs have been implemented for the general
      population; however, dermatology appointment wait times continue to be long.
      Changes in scheduling would allow patients with suspicious skin lesions access to
      more immediate care. OBJECTIVES: The objective was to introduce a method for
      decreasing dermatology appointment wait times to allow patients with a high-risk
      skin lesion to be seen in a more efficient manner. METHODS: A telephone screening
      method was developed to allow for the most suspicious lesions to be seen within
      72 hours if the patient wished to do so; appointment time slots were left open in
      physician schedules to accommodate these patients; and wait time, procedure, and
      treatment data were collected and compared against national wait time data.
      RESULTS: A total of 233 patients were seen during this study. A total of 146 of
      these patients were diagnosed with a cancerous or precancerous lesion. This was
      63% of the total study population. The mean wait time in actual working days was
      7.44 for this same period. CONCLUSION: This program substantially decreased
      patient anxiety, increased patient satisfaction, increased public relations for
      the practice, and increased public awareness of skin cancer. The Derm Access
      strategy can be implemented in any practice to reduce wait times for suspicious
      skin lesions.

PMID- 17199656
TI  - Baseline quality of life and anxiety in solid organ transplant recipients: a
      pilot study.
AB  - BACKGROUND: Solid organ transplant recipients on high doses of immunosuppression
      are at increased risk for the development of nonmelanoma skin cancer (NMSC).
      OBJECTIVE: The objective was to assess the possible factors impacting quality of
      life (QOL) in solid organ transplant recipients. METHODS: Patients were seen in a
      dermatology clinic integrated within the transplant center at a university-based
      hospital. One anxiety questionnaire and three QOL questionnaires were
      administered to each patient. A regression model was used to determine possible
      predictors of anxiety and lower QOL. RESULTS: The baseline scores on the QOL
      instruments and anxiety questionnaire indicate poor organ-specific and general
      QOL as well as high levels of anxiety. Time since transplant was predictive of
      lower QOL as measured by Skindex-16 (p<.01). While not significant, number of
      NMSCs correlated with higher anxiety as measured by the STAI (p=.055).
      CONCLUSIONS: While transplant patients enjoy longer survival, the quality of the
      extended life has room for improvement. Future studies will determine how QOL
      changes over time as these patients develop more numerous and aggressive skin
      cancers. Intervention with regular screening may not only lessen morbidity
      associated with skin cancer but may improve overall QOL in the posttransplant
      period.

PMID- 17199658
TI  - Panfacial squamous cell carcinoma.

PMID- 17199659
TI  - Instrument for biopsy of oral lesions: an improved chalazion forceps.

PMID- 17199661
TI  - Are melanocytic nevi influenced by pregnancy? A dermoscopic evaluation.
AB  - BACKGROUND: Dermoscopic data of melanocytic nevi (MN) in pregnancy are very
      limited and related to small groups of women. OBJECTIVE: This study
      systematically analyzes dermoscopic parameters in a wide series of MN during and
      after pregnancy. METHODS: Eighty-six MN on the back of 47 women were studied.
      Dermoscopic parameters, total dermoscopic score (TDS) according to Stolz's ABCD
      rule, and the sizes of the nevi were evaluated over time. RESULTS: Progressive
      lightening of the nevi resulted at the end of pregnancy (p<.05) and after
      delivery (p<.001). Pigment network showed a progressive reduction in prominence
      and thickness (end of pregnancy, p<.05; after delivery, p<.01). At the end of
      pregnancy, vessels increased (p<.05) and a higher TDS was observed, with a
      significant reduction in both after delivery (vessels, p<.05; TDS, p<.01). Area
      changes were not statistically significant. CONCLUSIONS: At the end of pregnancy,
      both vascular structures and TDS increased. These modifications were transient as
      the nevi recovered their prior appearance after delivery. The results indicate
      that an intrinsic influence of pregnancy may induce structural modifications
      without influencing the size of the nevi. Behavioral factors during the
      observational period, like a reduced exposure to sunlight reported by most of the
      women, may have influenced other characteristics, like global pigmentation and
      pigment network. The authors thank the Fondazione Cassa di Risparmio di Ferrara
      for its financial support, which enabled them to acquire the instrumentation
      necessary for this study.

PMID- 17199662
TI  - Burow's wedge advancement flap for lateral forehead defects.

PMID- 17199663
TI  - Dermoscopic-pathologic correlation in an unusual case of pigmented basal cell
      carcinoma.

PMID- 17199664
TI  - Cutaneous cartilaginous tumor.

PMID- 17199665
TI  - Mohs micrographic surgery and partial amputation preserving function and
      aesthetics in digits: case reports of invasive melanoma and digital
      dermatofibrosarcoma protuberans.

PMID- 17199666
TI  - Pigmented Bowen's disease clinically mimicking melanoma of the nail.

PMID- 17199667
TI  - T- and B-cutaneous pseudolymphomas treated by surgical excision and immediate
      reconstruction.

PMID- 17199668
TI  - NewFill for skin augmentation: a new filler or failure?

PMID- 17199670
TI  - A convenient source of carbon dioxide for sclerosant foams.

PMID- 17199671
TI  - Letter: injectable silicone for painful interdigital neurovascular clavi and
      verrucae.

PMID- 17199672
TI  - Successful use of botulinum toxin a for the treatment of neck and anterior chest
      wall flushing.

PMID- 17199674
TI  - Debridement and wound bed preparation.
AB  - Debridement can play a vital role in wound bed preparation and the removal of
      barriers that impair wound healing. In accordance with the TIME principles,
      debridement can help remove nonviable tissue, control inflammation or infection,
      decrease excess moisture, and stimulate a nonadvancing wound edge. There are many
      types of debridement, each with a set of advantages and disadvantages that must
      be clearly understood by the healthcare team. Failure to use the correct
      debridement method for a given type of wound may lead to further delays in
      healing, increase patient suffering, and unnecessarily increase the cost of care.
      This review article discusses the various methods of debridement, describes
      currently available debriding agents, evaluates the clinical data regarding their
      efficacy and safety, and describes strategies for the management of problematic
      nonhealing wounds.

PMID- 17199675
TI  - The use of systemic antibiotics in the treatment of chronic wounds.
AB  - The role of microorganisms in the etiology and persistence of chronic wounds
      remains poorly understood. The chronic wound bed houses a complex
      microenvironment that typically includes more than one bacterial species.
      Difficulty lies in determining when the presence of bacteria impedes wound
      healing, thereby warranting intervention. Indications for antibiotic therapy and
      optimal treatment regimens are ill defined. The goal of this article is to
      describe the appropriate role of systemic antibiotics in the management of
      chronic wounds. A common sense approach will be offered based on six clinically
      pertinent questions: Is infection present? Are systemic antibiotics necessary?
      Should treatment be enteral or parenteral? What antibiotic or combination of
      antibiotics should be used? What should be the duration of therapy? What special
      circumstances are present (i.e., concomitant illnesses, potential drug-drug
      interactions) that can impact therapy?

PMID- 17199676
TI  - Compression modalities and dressings: their use in venous ulcers.
AB  - Among the standard of care for venous ulcer treatment are the use of compression
      therapy to reverse the effect of venous hypertension and the use of occlusive
      dressings to maintain a moist wound-healing environment and for treatment of
      abnormalities of the ulcer bed. The use of multilayered elastic bandages for
      compression in patients with normal arterial flow currently provides the
      treatment with the highest level of evidence for treatment of venous ulcers.
      Additionally, treatment of the ulcer bed, especially with cadexemer iodine
      dressings, is also supported by evidence from randomized controlled trials,
      whereas newer dressings provide less well proven alternative opportunities to
      speed the healing of venous ulcers.

PMID- 17199677
TI  - Treatment of diabetic ulcers.
AB  - Diabetic ulcers are chronic wounds that are the result of repetitive trauma in
      the insensate foot. The presence of infection and peripheral vascular disease
      makes the treatment of these wounds demanding and requires a multidisciplinary
      approach. The main principles of the management include adherence to the
      principles of good wound care, such as aggressive debridement of all non-viable
      tissue, adequate off-loading of pressure, prompt treatment of infection and moist
      wound dressings. Over the last decade, new therapeutic modalities, including
      growth factors and living skin equivalents, have been available to the practicing
      physicians. Judicious use of advanced wound care products may provide the best
      means of treating these challenging wounds in an efficient and cost-effective
      way.

PMID- 17199678
TI  - Prevention and management of pressure ulcers.
AB  - Pressure ulcers represent a major health problem causing a considerable amount of
      suffering for patients and a high financial burden for healthcare systems. The
      geriatric population with an increased risk of pressure ulcer development is
      rising constantly as a result of chronic degenerative diseases that can lead to
      prolonged immobilization and poor nutrition. Evidence clearly indicates that
      preventive measures are essential to reduce the prevalence rates of pressure
      ulcers; therefore healthcare professionals must be able to identify the
      appropriate strategies to adopt, in order to meet the individual patient's
      requirements. Important advances have taken place in the world of pressure ulcer
      treatment during the past decade. These advances are reflected in the high rate
      of cures being obtained. This, together with the implementation of prevention
      guidelines, the excellent cost/effectiveness relationship of the techniques
      described, and other factors, means that the field of pressure ulcers management
      is no more an isolated and self-administered issue in medical practice. The areas
      discussed here are those in which there will be linear or, in some cases,
      exponential growth in the decades to come.

PMID- 17199679
TI  - Basic approach to inflammatory ulcers.
AB  - Cutaneous ulcers are a difficult problem. A multidisciplinary approach is often
      adapted in caring for patients with nonhealing wounds. Internists, surgeons,
      dermatologists, and nurses must work together to provide a patient with the most
      comprehensive care possible. Dermatologists are consulted for a number of
      reasons, particularly if the ulcers are secondary to an inflammatory process. In
      this discussion, we describe a basic and useful approach to the diagnosis and
      management of inflammatory ulcers. The spectrum of these conditions is wide,
      ranging from vasculitis, to pyoderma gangrenosum, to ulcers resulting from the
      antiphospholipid syndrome and cryoprecipitates. The present authors will
      emphasize that the approach needs to be all-encompassing, and not focused on the
      ulceration alone. Certain clues are critical to diagnosis. The management,
      whereas often difficult, can be very rewarding.

PMID- 17199680
TI  - Clinical research in dermatology: 10 steps to getting started.
AB  - Clinical research plays a very important role in the development of drugs and
      devices, including those for wound healing. The process of initiating a clinical
      trial can be rather daunting, particularly with the ever-increasing regulatory
      hurdles. Many clinicians are generally either not trained or have limited
      knowledge of these matters. In this short review, the present authors discuss the
      10 most important steps required in initiating a clinical trial. This information
      is applicable not only to wound healing studies, but also to other
      investigational trials.

PMID- 17199681
TI  - Wound bed score and its correlation with healing of chronic wounds.
AB  - Adequate wound bed preparation is essential for healing of leg ulcers, and
      consists of controlling exudate and edema, decreasing the bacterial burden,
      promoting healthy granulation tissue, and removing necrotic tissue. Currently,
      there is no classification system for wound bed preparation that has predictive
      value. Based on past work and the authors' experience, we have now developed and
      tested a new classification system that scores the following parameters: healing
      edges (wound edge effect), presence of eschar, greatest wound depth/granulation
      tissue, amount of exudate amount, edema, peri-wound dermatitis, peri-wound callus
      and or fibrosis, and a pink/red wound bed. Each parameter receives a score from 0
      (worst score) to 2 (best score), and all the parameter scores are added for a
      total score. Each wound can have a maximum score of 16 (the best score possible),
      to a minimum score of 0 (the worst score possible). We used this wound bed score
      (WBS) system in a study of 177 patients with venous ulcers who had been
      prospectively treated with and randomized to either conventional therapy
      (compression alone) or a living bilayered skin construct (BSC). We evaluated
      serial photographs at baseline to determine whether the results would be
      predictive of complete wound closure and could validate the WBS. We found that
      wounds that ultimately achieved full closure had a statistically significant
      higher WBS than those that did not heal (p = 0.0012). This was also true when
      separating wounds by treatment modality: standard therapy (p = 0.044) and
      treatment with a BSC (p = 0.011). When dividing the WBS in the following quartile
      groups: scores 4-10, 10-12, 12-13, and 13-16, the percentage of healed wounds
      correlated with the WBS (p = 0.0008). For all wounds, a one unit increase in
      total WBS resulted on average in a 22.8% increase in odds of healing (OR =
      1.228). This WBS seems to have validity in predicting complete wound closure in
      wounds treated with either standard therapy or advanced modalities, such as BSC.
      If confirmed and widely adopted in this and other types of wounds, it could be a
      useful tool in both the clinical and research setting.

PMID- 17199683
TI  - Reoperative surgery: importance of ectopic location and multigland disease.

PMID- 17199684
TI  - Away from surgery?

PMID- 17199685
TI  - Review of concepts of seroma formation and prevention in breast cancer surgery.

PMID- 17199686
TI  - Extracellular matrix as a bioactive material for soft tissue reconstruction.

PMID- 17199687
TI  - Reoperative parathyroid surgery: the importance of ectopic location and
      multigland disease.
AB  - BACKGROUND: Despite the availability of expert surgeons and preoperative imaging
      investigations, some patients require reoperation for persistent or recurrent
      hyperparathyroidisms. METHOD: Fifty consecutive patients were reviewed. RESULTS:
      There were 28 persistent cases (24 primary, 4 secondary) and 22 recurrent cases
      (15 primary, 7 secondary) and 98% had successful surgical treatment. Multigland
      disease was present in 24 of 39 (62%) of primary cases, 11 of 24 persistent and
      13 of 15 recurrent (P < 0.02). Four patients in the recurrent primary group had
      multiple endocrine neoplasia type 1, whereas the other 20 primary patients had
      sporadic multigland disease. Multigland disease was present in all secondary
      cases and was a very important factor in this entire series of patients (70%).
      Regrowth of a remnant of a gland biopsied or partially resected at an earlier
      operation was the cause of recurrence in 12 of 15 primary and 2 of 7 secondary
      cases (P < 0.05). The site of missed glands in persistent disease was ectopic in
      60%. Ectopic glands were found in the following sites: intrathyroidal 10 (8
      inferior and 2 superior), intrathymic 9, posterior mediastinum 4, base of skull
      2, carotid sheath 1 and supernumerary 5. Investigations to locate missing glands
      were positive in 28 of 43 sestamibi scans (65%), 14 of 34 ultrasound scans (41%),
      10 of 24 computed tomography scans (42%) and 11 of 13 selective venous sampling
      tests (85%). CONCLUSION: Some persistent cases are unavoidable because of ectopic
      locations and some recurrences are inevitable because of multigland disease.

PMID- 17199688
TI  - Localization and surgical treatment of the pancreatic insulinomas.
AB  - OBJECTIVES: Insulinomas are rare tumours that originate from the islet cells of
      the pancreas. The aims of this study were to gain an understanding of the
      clinical features of insulinomas and to establish the diagnostic and therapeutic
      strategies. METHODS: A review was carried out in 20 patients with insulinoma
      surgically treated in our institution over the last 10 years. Presenting
      symptoms, biochemical studies, preoperative and intraoperative localization
      studies, operative management and complications were analysed. RESULTS: The male
      to-female ratio was 8:12, with a mean age of 46.4 years. Each patient suffered
      from significant neuroglycopenic symptoms, usually manifested by dizziness,
      sweating, headache and confusion. The preoperative median serum levels of
      glucose, insulin and C-peptide at the termination of the fast were 37.5 mg/dL,
      23.5 microU/mL, 5.6 ng/mL, respectively. Preoperative tumour localization was
      achieved by means of ultrasonography (US), computed tomography, selective
      angiography or intra-arterial calcium injection with hepatic venous sampling, and
      sensitivities of these examinations were 81.8, 73.7, 94.1 and 100%, respectively.
      Intraoperative localization was carried out by a combination of manual palpation
      and intraoperative US with retrospective sensitivities of 80 and 100%,
      respectively. Enucleation was carried out in 16 patients and distal
      pancreatectomy in 4. The mortality and morbidity rates were 0 and 10%,
      respectively. One patient developed late diabetes mellitus type 1 after distal
      pancreatectomy. CONCLUSIONS: We conclude that the diagnosis of insulinoma can be
      made on the basis of the results of a supervised fast, careful palpation with
      intraoperative US is essential for intraoperative detection of insulinomas and
      surgical resection is the best choice for treatment of benign insulinomas.

PMID- 17199689
TI  - Surgical inclination and anatomy teaching at the University of Auckland.
AB  - BACKGROUND: Medical graduate interest in surgery has declined and medical
      students are less capable in anatomy than they once were. Declining interest in
      surgery is because of factors, including growing number of women entering medical
      school. There has been less emphasis in teaching anatomy at various medical
      schools in recent years. The aim of this study is to quantify surgical
      inclination in Auckland medical students to assess whether gender differences
      exist in surgical inclination and determine confidence in anatomy knowledge and
      resources used by Auckland medical students. METHOD: Survey design was cross
      sectional and included 25-point questionnaire using Likert scale response ranking
      and tick box replies. Two hundred and eighteen surveys were emailed to
      functioning addresses of fourth and fifth year students at University of
      Auckland, School of Medicine, New Zealand. RESULTS: Response rate was 71.6%.
      Twenty per cent of students were found to be surgically inclined (95% confidence
      interval, 0.15-0.26). The proportion of surgically inclined men was significantly
      higher than women (P < 0.05). Thirty-three per cent of all respondents (95%
      confidence interval, 0.26-0.41) felt their knowledge of anatomy was adequate to
      practice medicine safely. Textbooks and atlases were most commonly used to learn
      anatomy (P < 0.05). Radiology was the least commonly used method to learn anatomy
      (P < 0.05). Eighty-seven per cent (95% confidence interval, 0.81-0.92) of
      respondents agreed that revisiting dissection during surgical attachments would
      be helpful. CONCLUSION: Men are significantly more likely to be surgically
      inclined than women at the University of Auckland. A significantly greater
      proportion of students felt that their knowledge of gross anatomy was inadequate
      for safe medical practice. Students use traditional methods to learn anatomy more
      commonly than radiological methods. The majority of students surveyed would like
      to revisit cadaver dissection during clinical attachments in surgery.

PMID- 17199690
TI  - Surgical management of breast cancer in a small peripheral New Zealand hospital.
AB  - BACKGROUND: Peripheral hospitals are perceived to be at a disadvantage in
      providing treatment for breast cancer, especially with regard to breast
      conservative surgery (BCS) because of the requirement of adjuvant radiotherapy.
      Wairau Hospital is a 100-bed peripheral hospital in New Zealand with no on-site
      radiotherapy unit. METHODS: A retrospective audit of the surgical management of
      breast cancer between 1998 and 2002 was carried out. RESULTS: One hundred and
      fifty-seven presentations during the audit period. Despite the lack of tertiary
      resources, we report an overall BCS rate of 58.6%, consistent with the
      appropriate New Zealand guidelines. Of screen-detected cancers, 81.6% underwent
      BCS. Only five patients requested mastectomy and of those undergoing BCS, five
      patients refused subsequent adjuvant radiotherapy. This was because of frailty
      from age and comorbidities and the inconvenience of travel. CONCLUSION: High
      rates of BCS are possible in peripheral hospitals. We postulate that intensive
      support and a visiting outpatient oncological service help empower patients to
      seek BCS if appropriate. A strong partnership between surgical, radiological and
      oncological services is also vital.

PMID- 17199691
TI  - Breast specimen ultrasound and mammography in the prediction of tumour-free
      margins.
AB  - BACKGROUND: Adequacy of margins is important for local recurrence control in
      breast-conserving surgery for breast cancer. This study aims to compare the
      accuracy of intraoperative specimen ultrasonography (IOUS) and specimen
      mammography in the prediction of achieving adequate histologically tumour-free
      margins during breast-conserving surgery. METHODS: Between March 2003 and
      September 2004, a prospective study was carried out on 25 patients who underwent
      breast-conserving surgery. After wide excision, IOUS and specimen mammography
      were used to assess adequacy of margins. Further surgery was undertaken when
      either method showed an inadequate margin. The margins were assessed
      histologically and correlated with IOUS and mammographic findings. RESULTS: Using
      IOUS alone, higher rates of histologically tumour-free margins were achieved
      compared with mammography alone. Combined IOUS and mammography achieved similar
      or slightly higher rates of histologically tumour-free margins compared with IOUS
      alone. If the margin measured on IOUS is twice the desired histological margin,
      this will result in achieving a histologically tumour-free rate of >90%.
      Associated ductal carcinoma in situ was the only significant factor found to
      decrease the rate of achieving adequate margins. CONCLUSION: Intraoperative
      specimen ultrasonography is useful in predicting histologically tumour-free
      margins during breast conserving surgery for cancer.

PMID- 17199692
TI  - Selection of primary hip and knee arthroplasties for public hospitals in Western
      Australia: a clinical evidence approach.
AB  - BACKGROUND: The Australian Joint Registry records that there are approximately 84
      hip stem designs, 71 acetabular designs and 45 knee systems in common use in
      Australia, giving the surgeon an extensive and often bewildering choices.
      METHODS: Since the 1990s, there have been several attempts to rationalize the
      supply of the products of primary hip and knee arthroplasties to the public
      hospitals in Western Australia. To continue and improve the rationalization
      process, the recently awarded 'whole of health' tender was based on a thorough
      clinical and laboratory evaluation process. The method included commercial
      analysis by Health Supply Western Australia, clinical evaluation by a committee
      comprised of senior surgeons and technical assessment by biomedical engineers and
      scientists. The evaluation process was subdivided into qualitative criteria;
      being the commercial aspects of the tender (50%) and a fitness for purpose
      assessment comprising clinically based evidence (40%) and laboratory assessment
      of product quality (10%). RESULT: The tendering process concluded with the
      recommendation of 12 hip and 5 knee systems. CONCLUSIONS: A comprehensive method
      primarily based on clinical evidence was used to assess arthroplasty products
      tendered to Western Australia public hospitals. Generally, there was good
      compliance with the commercial aspects of the tender. In contrast, however,
      clinically based evidence assessment of many arthroplasty devices was difficult
      because of a distinct lack of quality published work. Inadequate quality control
      of several devices is also of concern. Evaluation of key performance indicators,
      including cost savings, acceptance by surgeons, tender compliance and revision
      rates, will determine the success of the tender.

PMID- 17199693
TI  - Experience of endoscopic ultrasound in an Australian tertiary hospital.
AB  - BACKGROUND: There is minimal prospective data on endoscopic ultrasound (EUS)
      experience in Australia. This study aimed to review the recent EUS experience of
      a single Australian tertiary hospital. METHODS: Data of all EUS carried out at St
      Vincent's Hospital, Melbourne, Australia were prospectively collected from August
      2002 to September 2005. Patient demographics, indications, anatomical sites of
      EUS and fine-needle aspiration (FNA) were extracted from the database. A subset
      of 231 patients were involved in a prospective study to assess the clinical
      effect of EUS: with accuracy and outcomes data derived from surgical histology
      and pre-EUS and post-EUS questionnaires. RESULTS: Five hundred and sixty-one
      procedures were carried out for 526 patients. Men comprised 57% (n = 300). Mean
      age was 60 years (range, 19-92 years). The indications were (i) oesophageal 30.7%
      (n = 172); (ii) pancreaticobiliary 29.6% (n = 166); (iii) mediastinal and lung
      20.7% (n = 116); (iv) gastric 15.9% (n = 89); and (v) duodenal 3.2% (n = 18).
      Endoscopic ultrasound-guided FNA was carried out in 30.3% procedures (170/561).
      Overall EUS accuracy was 84% (55/67 patients) and EUS-guided FNA accuracy was 88%
      (28/32 patients). There were no major complications. CONCLUSIONS: This is the
      largest reported Australian experience of EUS to date. Overall EUS was accurate,
      safe with no major complications or mortality and had useful outcomes. The role,
      expertise and accessibility of EUS in the Australian clinical setting are
      anticipated to continue to increase.

PMID- 17199694
TI  - New surgical consultants: is there a learning curve?
AB  - The purpose of this study was to determine whether newly established surgeons who
      have completed dedicated post-fellowship training are able to achieve surgical
      outcomes comparable to their more experienced peers. A cross-sectional study of
      consecutive patients undergoing total thyroidectomy (TT) or completion
      thyroidectomy was carried out. Outcomes measured included unplanned return to the
      operating theatre, postoperative infection, permanent recurrent laryngeal nerve
      (RLN) injury and permanent hypoparathyroidism. Outcomes were categorized
      according to whether surgery was carried out by an established surgeon (ES) or a
      newly appointed surgeon (NAS). Eight hundred and nine TT and completion
      thyroidectomy procedures were carried out in the period January 2002 to December
      2004. Of these, 515 (64%) were carried out by ES and 294 (36%) were carried out
      by NAS. The overall rate of permanent hypoparathyroidism and RLN injury was 1.4%
      (12/809) and 0.6% (5/809), respectively. The rate of permanent hypoparathyroidism
      was not significantly different between the two categories of surgeon (ES 1.35%
      vs NAS 1.7%; P = 0.7). The incidence of permanent RLN injury was not different
      between the two groups (ES 0.8% vs NAS 0.3%; P = 0.4). For NAS, the rate of
      permanent RLN injury for the first two years of independent practice did not
      differ significantly from 3 to 4 years of practice (0/123 vs 1/171; P = 0.4).
      Indications for surgery between the two groups were similar, with ES carrying out
      TT for benign goitre in 42% and cancer in 28%, and NAS 44 and 32%, respectively.
      Surgical outcomes for the newly established endocrine surgeon following
      subspecialty training are equivalent to those achieved by more experienced
      surgeons.

PMID- 17199695
TI  - Experience with the use of vacuum dressings in the management of acute
      enterocutaneous fistulas.
AB  - High-output enterocutaneous fistulas involving an open abdominal wound are a
      difficult management problem. We report our experience on the use of vacuum
      dressings. The potential benefits, problems and new recommendations for the use
      of vacuum dressings in the management of enterocutaneous fistulas are discussed.

PMID- 17199696
TI  - Concepts of seroma formation and prevention in breast cancer surgery.
AB  - BACKGROUND: Seroma formation is the commonest early sequel to breast cancer
      surgery especially when axillary dissection is undertaken. It is associated with
      significant morbidity and financial burden. The main pathophysiology of seroma is
      still poorly understood and remains controversial. The optimal ways to reduce the
      incidence of seroma formation are unknown. The aim of this paper is to review the
      concepts of pathophysiology of seroma formation following mastectomy and breast
      conserving surgery for cancer. The various techniques in practice to reduce its
      incidence and treatment are outlined. METHOD: MEDLINE search of published work on
      the subject with respect to its pathophysiology, prevention and treatment was
      carried out. Manual retrieval of relevant articles in the reference lists of the
      original papers from the MEDLINE was then carried out. RESULT: The
      pathophysiology and mechanism of seroma formation in breast cancer surgery
      remains controversial and not fully understood. Methods of prevention and
      treatment of seroma remain varied and inconclusive. CONCLUSION: Evidence suggests
      an increase in the incidence of seroma because of thermal trauma from
      electrocautery dissection, but this is indispensable for surgical haemostasis.
      Obliteration of dead space by various flap apposition techniques has been shown
      to be advantageous in reducing incidence and volume of seroma. Low-pressure
      suction drainage reduces seroma volume and duration of drainage leading to
      earlier drain removal. Preventive measures have to be tailored according to
      individual patient and operative factors.

PMID- 17199698
TI  - Magnification chromo-colonoscopy.
AB  - Chromoscopic colonoscopy using indigo carmine is indispensable for the accurate
      detection of flat neoplastic lesions. In particular, the dye spray technique
      facilitates the detection of both flat hyperplastic polyps and highly dysplastic
      lesions. However, magnification chromo-colonoscopy discriminates adenomas from
      hyperplastic polyps with greater accuracy than conventional methods by showing
      distinct and visible pit patterns. A pit pattern represents crypt orifices, which
      reflect the underlying histological structures and colonoscopists can make
      histological predictions by observing the pit patterns without obtaining biopsy
      specimens. The pit patterns are classified as types I, II, IIIL, IIIs, IV and V
      based on histological characterization of normal mucosa, hyperplastic polyp,
      polypoid adenoma, flat adenoma, tubulo-villous adenoma and cancerous tissue,
      respectively. In previous reports, overall accuracy ranged from 80 to 95%. In
      addition, magnification chromo-colonoscopy is useful for the diagnosis of early
      cancer associated with substantial invasion of the submucosa, in which type V
      pits are subclassified as types V-I and V-N. The presence of type V-N pits is
      significant in correlation to cancer with substantial invasion of the submucosa.
      Magnification chromo-colonoscopy is useful in clinical decision-making when
      deciding whether endoscopic resection or bowel resection is the appropriate
      initial procedure to treat lesions.

PMID- 17199697
TI  - Extracellular matrix as a bioactive material for soft tissue reconstruction.
AB  - The extracellular matrix (ECM) directs all phases of healing following trauma or
      disease and is therefore a natural source of prosthetic mesh material that can be
      used strategically to induce the repair and restoration of soft tissues following
      surgery. Biomaterials such as Surgisis (Cook Biotech Incorporated, West
      Lafayette, IN, USA), which are derived from natural ECM, provide the
      extracellular components necessary to direct the healing response, allow for the
      proliferation of new, healthy tissue and restore tissue integrity to the damaged
      site. The 3-D organization of these extracellular components distinguishes the
      Surgisis mesh from synthetic materials and is associated with constructive tissue
      remodelling instead of scar tissue. Common features of this ECM-assisted tissue
      remodelling include angiogenesis, recruitment of circulating progenitor cells and
      constructive remodelling of damaged tissue structures. The tissue response to
      this biologic mesh is discussed in the context of recent reports on clinical
      hernia repair.

PMID- 17199699
TI  - Determining normal values for intra-abdominal pressure.
AB  - BACKGROUND: Intra-abdominal pressure (IAP) measurements can be used for the early
      detection and management of the abdominal compartment syndrome. IAP values are
      widely thought to be atmospheric or subatmospheric. However, there are no reports
      that describe normal IAP values using urinary bladder pressure measurements in
      patients not suspected of having a raised IAP level. This study sought to
      determine these normal values to aid our interpretation of IAP measurements in
      post-surgical patients or patients with suspected increased IAP. METHODS: Urinary
      bladder pressure measurements were carried out in 40 men and 18 women awake
      medical or non-abdominal surgery inpatients with existing indwelling catheters.
      Measurements were made in the supine, 30 degrees and 45 degrees sitting
      positions. Comparisons were carried out to determine the effects on urinary
      bladder pressure of body position, sex and a suspected diagnosis of benign
      prostatic hypertrophy. RESULTS: Median values for IAP were higher if measured in
      a more upright position (P < 0.0001). Median values were supine, 9.5 cmH2O
      (range, 1-18 cmH2O); 30 degrees upright, 11.5 cmH2O (range, 3-19 cmH2O); and at
      45 degrees upright, 14.0 cmH2O (range, 4-22 cmH2O). Measurements recorded were
      neither atmospheric nor subatmospheric. IAP was higher in men compared with women
      in the supine and 30 degrees positions (P < 0.05) but not in the 45 degrees
      position (P = 0.083). There was no significant difference between patients with
      and without suspected benign prostatic hypertrophy. CONCLUSIONS: Normal IAP using
      urinary bladder pressure in awake patients are above atmospheric pressure. As a
      patient is moved from the supine into the upright position, IAP measurements
      increase.

PMID- 17199700
TI  - Extended medial gastrocnemius myocutaneous flap in repair of the quadriceps
      extension mechanism.
AB  - The gastrocnemius muscle is versatile in flap repair of defects from anterior
      knee to lower leg. We describe a case of extensor reconstruction using an
      extended medial gastrocnemius myocutaneous flap. A medial gastrocnemius flap was
      raised distal to its musculotendinous insertion. At its point of rotation, it was
      anchored to the anterior periosteum of the tibia, hence obliterating dead space
      and recreating the extensor mechanism of the knee. The patient had no flap loss
      and was able to ambulate independently. He showed no extensor lag. Our flap is
      unique in that it is the only medial gastrocnemius flap that has shown no
      extensor lag as well as complete flexion of the knee following a disrupted entire
      quadriceps mechanism. It is also the first myocutaneous gastrocnemius flap that
      has been described for this purpose.

PMID- 17199701
TI  - The Gordon Gordon-Taylor Memorial Lecture: surgical giants and giants among
      surgeons--the case of Abraham Colles.
AB  - Sir Gordon Gordon-Taylor was a surgical giant and a giant among surgeons. There's
      a distinction between the two. Surgical giants are technical geniuses who pave
      the way for others and set the standards against which others can measure their
      performance. Giants among surgeons contribute other things to the science and
      practice of surgery and sometimes to fields outside surgery. By these measures,
      Abraham Colles was not a surgical giant. He thought, wrote and taught about his
      interests. He enhanced the reputation of Irish surgery. In retrospect, his
      science and his ethics seem flawed by modern standards, but by the measures of
      his own time he was a model investigator and a man of outstanding moral probity.
      He is remembered for the eponymous Colles's fracture and for Colles's fascia and
      ligament. He held the Chair of Anatomy and Surgery in Dublin for 32 years and
      drew the admiration and affection of his contemporaries, colleagues and students.
      He was a giant among surgeons, and his name deserves commemoration.

PMID- 17199703
TI  - Adrenaline-induced digital ischaemia reversed with phentolamine.
AB  - Adrenaline autoinjectors are widely prescribed for self-treatment of anaphylactic
      syndromes. Accidental misfire into digits can cause prolonged significant
      ischaemia with serious outcomes. Phentolamine is a readily available treatment,
      which is easily and safely given in the emergency setting.

PMID- 17199704
TI  - Reiteration of core principles of the Keystone island flap.

PMID- 17199705
TI  - Keystone island flaps: a radiation oncologist's perspective.

PMID- 17199706
TI  - Occupation and carpal tunnel syndrome.

PMID- 17199707
TI  - Occupation and carpal tunnel syndrome.

PMID- 17199708
TI  - Occupation and carpal tunnel syndrome.

PMID- 17199710
TI  - Surgery is not just an art.

PMID- 17199711
TI  - Incidence and outcomes of knee and hip joint replacements in veterans and
      civilians.

PMID- 17199712
TI  - Incidence and outcomes of knee and joint replacement in veterans and civilians.

PMID- 17199713
TI  - Ectopic fat accumulation and metabolic syndrome.
AB  - The recent escalation of obesity from an individual health problem to a major
      public health issue reaching epidemic proportions has drawn attention to a
      constellation of abnormalities (abdominal obesity, hypertension and
      dyslipidaemia) collectively referred to as metabolic syndrome. As an indicator of
      insulin resistance and a harbinger of diabetes, this syndrome has been associated
      with major cardiovascular mortality and morbidity. Yet, the exact
      pathophysiological events leading to the development of metabolic syndrome remain
      unknown. We review some of the current literature on the pathogenesis of
      metabolic syndrome with an emphasis on the role of ectopic lipid accumulation.

PMID- 17199714
TI  - Therapeutic aspects of growth hormone and insulin-like growth factor-I treatment
      on visceral fat and insulin sensitivity in adults.
AB  - Growth hormone (GH) is generally considered to exert anti-insulin actions,
      whereas insulin-like growth factor I (IGF-I) has insulin-like properties.
      Paradoxically, GH deficient adults and those with acromegaly are both predisposed
      to insulin resistance, but one cannot extrapolate from these pathological
      conditions to determine the normal metabolic roles of GH and IGF-I on glucose
      homeostasis. High doses of GH treatment have major effects on lipolysis, which
      plays a crucial role in promoting its anti-insulin effects, whereas IGF-I acts as
      an insulin sensitizer that does not exert any direct effect on lipolysis or
      lipogenesis. Under physiological conditions, the insulin-sensitizing effect of
      IGF-I is only evident after feeding when the bioavailability of circulating IGF-I
      is increased. In contrast, many studies in GH deficient adults have consistently
      shown that GH replacement improves the body composition profile although these
      studies differ considerably in terms of age, the presence or absence of multiple
      pituitary hormone deficiency, and whether GH deficiency was childhood or adult
      onset. However, the improvement in body composition does not necessarily
      translate into improvements in insulin sensitivity presumably due to the anti
      insulin effects of high doses of GH therapy. More recently, we have found that a
      very low dose GH therapy (0.1 mg/day) improved insulin sensitivity without
      affecting body composition in GH-deficient adults and in subjects with metabolic
      syndrome, and we postulate that these effects are mediated by its ability to
      increase free 'bioavailable' IGF-I without the induction of lipolysis. These
      results raise the possibility that this low GH dose may play a role in preventing
      the decline of beta-cell function and the development of type 2 diabetes in these
      "high risk" subjects.

PMID- 17199715
TI  - Oral antidiabetic agents as cardiovascular drugs.
AB  - The increased risk of cardiovascular disease associated with type 2 diabetes is
      well documented. Lesser degrees of abnormal glucose metabolism including impaired
      fasting glycaemia and impaired glucose tolerance are also associated with
      increased cardiovascular risk. Studies showing improved cardiovascular outcomes
      with oral antidiabetic agents are limited, with the UKPDS demonstrating improved
      macrovascular outcomes only in a subgroup of obese patients with type 2 diabetes
      treated with metformin, and the heavily criticized STOP NIDDM trial showing a
      reduction in the number of cardiovascular events with the alpha glucosidase
      inhibitor acarbose. In recent years there has been an increase in the number of
      oral antidiabetic drugs available to treat the hyperglycaemia of diabetes. Some
      of these drugs have complex metabolic properties, additional to their
      antihyperglycaemic effect, improving endothelial function and markers of
      atherogenesis, with the potential to reduce cardiovascular morbidity and
      mortality, as supported by the recently published results of the PROACTIVE study.
      The results of further long-term cardiovascular outcome studies with these newer
      agents are awaited.

PMID- 17199716
TI  - Insulin glargine benefits patients with type 2 diabetes inadequately controlled
      on oral antidiabetic treatment: an observational study of everyday practice in
      12,216 patients.
AB  - AIMS: This observational study aimed to investigate the long-term efficacy and
      safety of adding insulin glargine (LANTUS((R))) to support oral antidiabetic
      (OAD) treatment in patients with type 2 diabetes in everyday practice. METHODS: A
      9-month, open-label, multicentre, observational study, with an optional 20-month
      extension phase, in which add-on insulin glargine therapy was initiated in 12,216
      patients with type 2 diabetes inadequately controlled on OADs. The insulin
      glargine dose was adjusted at the physician's discretion, reflecting everyday
      practice. The main outcome measures were changes in HbA(1c), fasting blood
      glucose (FBG), insulin dose and body mass index (BMI). RESULTS: At baseline, mean
      (+/- s.d.) age was 63.9 +/- 11.3 years; disease duration was >5 years in 47% of
      patients, 1-5 years in 39% of patients and <1 year in 10% of patients, while 4%
      of patients were newly diagnosed. Addition of insulin glargine to OAD therapy led
      to reductions in mean HbA(1c) (-1.5% from 8.7%) and FBG (-69 mg/dl from 202
      mg/dl) levels after 3 months, which were maintained after 9 months [HbA(1c): 
      1.7%; FBG: -71 mg/dl (-3.9 mmol/l)] without an increase in BMI. Similar glycaemic
      control was observed after 20 months in the 2721 patients in the extension study.
      Adverse drug reactions were documented in 26 patients (0.2%). Of 47 adverse
      events documented, 19 were due to hypoglycaemia. CONCLUSIONS: In everyday
      practice, patients with type 2 diabetes who are inadequately controlled on OADs
      benefit from add-on basal insulin treatment with insulin glargine as they
      demonstrate improved glycaemic control without weight gain.

PMID- 17199718
TI  - Prevalence and trends of metabolic syndrome in Korea: Korean National Health and
      Nutrition Survey 1998-2001.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a major international health problem.
      Limited information is available about the prevalence of MetS in Asia, especially
      in Korea. OBJECTIVE: To examine the prevalence and trends of MetS in a Korean
      population. In addition, we investigated the risk factors associated with MetS.
      DESIGN AND PARTICIPANTS: A total of 7445 participants aged >/=20 years from the
      Korean National Health and Nutrition Survey (KNHNS) 1998 and 5964 participants
      from the KNHNS 2001 were included in this analysis. The KNHNS is a cross
      sectional health survey of a nationally representative sample of the Korean
      population. The prevalence of MetS was determined using the National Cholesterol
      Education Program Adult Treatment Panel III criteria and the Asia-Pacific
      criteria for obesity based on waist circumference (APC-WC). RESULTS: Using the
      ATP III criteria, the age-adjusted prevalence of MetS among Korean adults was
      15.7% (13.7% male, 17.8% female) in 1998 and 14.4% (13.0% male, 16.2% female) in
      2001. Using the APC-WC criteria, the prevalence was 21.6% (19.4% male, 23.9%
      female) in 1998 and 21.4% (20.1% male, 23.4% female) in 2001. Of the five MetS
      components, increasing trends were found between 1998 and 2001 in the prevalence
      of hypertriglyceridaemia, low high-density lipoprotein cholesterol and central
      obesity for both men and women. Age, sex, body mass index and a family history of
      diabetes were associated with MetS. CONCLUSIONS: These results from a
      representative sample show that MetS is common in Korean adults. A systemic
      public health programme is required to prevent future increases in diabetes and
      cardiovascular complications.

PMID- 17199717
TI  - Mechanism for blockade of angiotensin subtype 1 receptors to lower plasma glucose
      in streptozotocin-induced diabetic rats.
AB  - AIMS: We investigated the mechanism(s) by which valsartan, a selective antagonist
      of angiotensin subtype 1 (AT(1)) receptor, decreased plasma glucose in
      streptozotocin (STZ)-induced diabetic rats. METHODS: The plasma glucose
      concentration was assessed by the glucose oxidase method. The concentration of
      beta-endorphin in plasma or medium incubating adrenal medulla was measured using
      an enzyme-linked immunosorbent assay. The mRNA levels of the subtype 4 form of
      glucose transporter (GLUT4) in soleus muscle and phosphoenolpyruvate
      carboxykinase (PEPCK) in the liver were detected by Northern blotting analysis,
      while the protein levels of GLUT4 in isolated soleus muscle and hepatic PEPCK
      were investigated using Western blotting analysis. RESULTS: A single intravenous
      injection of valsartan dose-dependently increased plasma beta-endorphin-like
      immunoreactivity (BER) in parallel with the lowering of plasma glucose
      concentration in STZ-induced diabetic rats. Naloxone and naloxonazine inhibited
      the plasma glucose-lowering action of valsartan at doses sufficient to block
      opioid micro-receptors. In contrast to its action in wild-type diabetic mice,
      valsartan failed to modify plasma glucose in opioid micro-receptor knockout
      diabetic mice. Bilateral adrenalectomy in STZ-induced diabetic rats eliminated
      both the plasma glucose-lowering action and the plasma BER-elevating action of
      valsartan. In the isolated adrenal medulla of STZ-induced diabetic rats,
      angiotensin II (Ang II) or valsartan did not affect spontaneous BER secretion.
      Activation of cholinergic receptors by 1.0 micromol/l acetylcholine (ACh)
      enhanced BER secretion from the isolated adrenal medulla of STZ-induced diabetic
      rats, but not in the presence of 1.0 nmol/l Ang II, while valsartan reversed this
      inhibition by Ang II in a concentration-dependent manner. Treatment of STZ
      induced diabetic rats with valsartan (0.2 mg/kg) three times daily for 3 days
      resulted in an increase in gene expression of GLUT4 in soleus muscle and impeded
      the reduction of elevated mRNA or protein level of hepatic PEPCK. Both of these
      effects were blocked by opioid micro-receptor antagonist. CONCLUSIONS: The
      results suggest that blockade of AT(1) receptor by valsartan may enhance the
      adrenal beta-endorphin secretion induced by ACh, activating the opioid micro
      receptors to increase glucose utilization and/or to decrease hepatic
      gluconeogenesis, resulting in the reduction of plasma glucose in STZ-induced
      diabetic rats.

PMID- 17199719
TI  - Brain-derived neurotrophic factor enhances glucose utilization in peripheral
      tissues of diabetic mice.
AB  - AIMS: Repetitive subcutaneous or intracerebroventricular administration of brain
      derived neurotrophic factor (BDNF) ameliorates glucose metabolism and enhances
      energy expenditure in obese diabetic C57BL/KsJ-db/db mice. To explore the
      mechanism of action through which BDNF regulates glucose metabolism, we examined
      the effects of BDNF on glucose utilization and norepinephrine (NE) content in
      peripheral tissues of diabetic mice. METHODS: [(14)C]2-deoxyglucose ([(14)C]2-DG)
      uptake into peripheral tissues was analysed after intravenous injection of
      [(14)C]2-DG in db/db and normal C57BL/6 mice, and [(14)C]2-DG uptake and NE
      content in peripheral tissues were analysed after subcutaneous administration of
      BDNF (20 mg/kg) to male db/db and normal mice for 8 days. RESULTS: [(14)C]2-DG
      uptake in the diaphragm, heart, gastrocnemius, soleus and interscapular brown
      adipose tissue (BAT) of db/db mice was significantly lower than in normal mice.
      Repetitive administration of BDNF to db/db mice for 8 days enhanced [(14)C]2-DG
      uptake in the diaphragm, heart, soleus, BAT and liver. The NE content in heart,
      skeletal muscle, interscapular BAT and liver of db/db mice given BDNF was high
      compared with db/db mice given vehicle, whereas no significant change in NE
      content in peripheral tissues was observed in normal mice given BDNF and those
      given vehicle. BDNF did not affect [(14)C]2-DG uptake or NE content in the white
      adipose tissue of db/db mice. CONCLUSIONS: These data indicate that BDNF
      ameliorates glucose metabolism by enhancement of glucose utilization in muscle
      and BAT, with this effect caused by modulation of the central and peripheral
      nervous systems.

PMID- 17199720
TI  - The relationship between insulin resistance and dyslipidaemia in cigarette
      smokers.
AB  - AIM: Considerable evidence shows that cigarette smokers tend to have the
      dyslipidemic pattern of high plasma triglyceride (TG) and low high-density
      lipoprotein cholesterol (HDL-C) concentrations, a highly atherogenic lipoprotein
      profile also typical of the insulin-resistant state even in the absence of
      cigarette smoking. However, because cigarette smokers are frequently insulin
      resistant, it is unclear if this dyslipidaemia is secondary to smoking, per se,
      or simply to the fact that smokers tend to be insulin resistant. The present
      study was initiated to determine whether this dyslipidaemia prevalent in
      cigarette smokers and characteristic of insulin-resistant individuals is a
      function of cigarette smoking or of insulin resistance. METHODS: As measured
      using vertical auto profile-II methodology, the lipid and lipoprotein
      concentrations were compared in 34 cigarette smokers divided into insulin
      sensitive and insulin-resistant subgroups. The two groups were similar in age and
      body mass index, differing only in their insulin-mediated glucose uptake as
      quantified by the steady-state plasma glucose concentration determined during the
      insulin suppression test. RESULTS: While levels of TG and very low-density
      lipoprotein cholesterol (VLDL-C) were significantly elevated in insulin-resistant
      cigarette smokers, total cholesterol (C), low-density lipoprotein cholesterol
      (LDL-C), narrow-density (ND) LDL-C, intermediate-density lipoprotein-C (IDL-C),
      HDL-C and non-HDL-C were not different in the two groups. The insulin-resistant
      smokers also had a preponderance of small, dense LDL particles, while the reverse
      was true of the insulin-sensitive cigarette smokers. CONCLUSIONS: These data
      suggest that the dyslipidaemia previously attributed to smoking occurs primarily
      in those smokers who are also insulin resistant.

PMID- 17199721
TI  - The impact of long chain n-3 polyunsaturated fatty acid supplementation on
      inflammation, insulin sensitivity and CVD risk in a group of overweight women
      with an inflammatory phenotype.
AB  - BACKGROUND: Inflammation is strongly related to obesity and the risk of
      cardiovascular disease (CVD). The metabolic benefits of long chain (LC) n-3
      polyunsaturated fatty acid (PUFA) may be attributable to its anti-inflammatory
      properties. OBJECTIVE: To investigate whether an individual's habitual
      inflammatory status influences the impact of a LC n-3 PUFA intervention on CVD
      risk. DESIGN: The study was a randomized crossover design. Subjects received LC n
      3 PUFA capsules or a placebo for 12 weeks, with 4-week washout between phases.
      Thirty women, in the top and bottom tertiles of baseline sialic acid
      concentration, formed raised inflammatory status (top, n = 12) and reference
      (bottom, n = 18) groups. Baseline data were analysed using one-way anova,
      differences between treatment phases were calculated at each timepoint and
      analysed using a random effects model. RESULTS: At baseline, the raised
      inflammatory status group had significantly higher body mass index and area under
      the curve (AUC) insulin than the reference group. With LC n-3 PUFA
      supplementation, both groups showed significantly higher plasma eicosapentaenoic
      acid and docosahexaenoic acid at 4 and 12 weeks (p < 0.001), and lower
      triacylglycerols (4 weeks p < 0.01 and 12 weeks p < 0.05). The difference in AUC
      insulin between the two treatment phases at 12 weeks was significantly greater in
      the raised inflammatory status group compared to the reference group (p < 0.05).
      Inflammatory markers were significantly lower after 12 weeks LC n-3 PUFA
      supplementation compared to baseline (C-reactive protein p < 0.05 and interleukin
      6 p < 0.01), but there was no significant group effect. CONCLUSIONS: Habitual
      inflammatory status influences the impact of LC n-3 PUFA supplementation, but it
      is not clear whether the effect of LC n-3 PUFA on AUC insulin is mediated through
      inflammatory mechanisms.

PMID- 17199722
TI  - Apolipoprotein E genotype affects the response to lipid-lowering therapy in
      Chinese patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To evaluate the effect of apolipoprotein E (apoE) genotype on baseline
      lipid levels and the response to hydroxy-methyl glutaryl coenzyme A reductase
      inhibitors (statins) therapy in Chinese patients with type 2 diabetes mellitus
      (DM). RESEARCH DESIGN AND METHODS: We consecutively recruited Chinese patients
      with type 2 DM requiring lipid-lowering therapy according to current guidelines.
      Patients were started on either simvastatin 10 mg daily or given an equivalent
      dose of lovastatin 20 mg. After 12 weeks of statin therapy, patients had fasting
      lipid profiles repeated. ApoE genotyping was performed by restriction fragment
      length polymorphism (RFLP). RESULTS: Ninety-six patients were studied. The
      epsilon3/epsilon3 genotype was in 62.5%, epsilon2/epsilon3 and epsilon3/epsilon4,
      16.7 and 20.8%, respectively. After adjusting for confounding variables, baseline
      total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels
      were significantly higher in those with epsilon3/epsilon4 compared with
      epsilon2/epsilon3 genotype (6.7 vs. 5.5 mm for TC, 4.5 vs. 3.6 mm for LDL-C; p =
      0.015 and p = 0.025, respectively). With statin therapy, epsilon3/epsilon4
      patients had significantly greater LDL-C lowering compared with epsilon2/epsilon3
      patients (48 vs. 27.7%; p = 0.04). There was no gender difference in baseline
      lipid parameters or response to statin therapy. CONCLUSIONS: ApoE genotype
      accounts for interindividual variability of baseline cholesterol levels, and
      response to statin therapy in Chinese patients with type 2 DM.

PMID- 17199723
TI  - Synergistic effects of conjugated linoleic acid and chromium picolinate improve
      vascular function and renal pathophysiology in the insulin-resistant JCR:LA-cp
      rat.
AB  - AIMS: Conjugated linoleic acid (CLA) is a natural constituent of dairy products,
      specific isomers of which have recently been found to have insulin sensitizing
      and possible antiobesity actions. Chromium is a micronutrient which, as the
      picolinate (CrP), has been shown to increase insulin sensitivity in animal
      models, including the JCR:LA-cp rat. We tested the hypothesis that these agents
      may have beneficial synergistic effects on the micro- and macrovasculopathy
      associated with hyperinsulinaemia and early type 2 diabetes. METHODS: Insulin
      resistant cp/cp rats of the JCR:LA-cp strain were treated with mixed isomers of
      CLA (1.5% w/w in the chow) and/or CrP at 80 microg/kg/day (expressed as Cr) from
      4 weeks of age to 12 weeks of age. Plasma insulin, lipid and adiponectin levels,
      aortic vascular function, renal function and glomerular sclerosis were assessed.
      RESULTS: CLA administration reduced food intake, body weight and fasting insulin
      in JCR:LA-cp rats. Plasma adiponectin levels were significantly elevated in rats
      treated with both CLA and CrP. Aortic hypercontractility was reduced and the
      relaxant response to the nitric oxide-releasing agent acetylcholine (Ach) was
      increased in CrP-treated rats. Striking reductions were also observed in the
      level of urinary albumin and the severity of glomerular sclerosis in rats treated
      specifically with CLA. CONCLUSIONS: CLA and CrP have beneficial effects
      ameliorating several of the pathophysiologic features of an insulin-resistant rat
      model. These supplements may be useful adjuncts in the management of patients
      with the metabolic syndrome and warrant further study.

PMID- 17199724
TI  - Weight changes following the initiation of new anti-hyperglycaemic therapies.
AB  - OBJECTIVE: The objective of this study was to quantify 1-year weight gain
      associated with the initiation of sulphonylurea (SU), metformin, insulin and
      thiazolidinedione (TZD) therapy in a representative real world population of type
      2 diabetic patients. RESEARCH DESIGN AND METHODS: The study population was 9546
      members of Kaiser Permanente North-west (KPNW) who initiated an anti
      hyperglycaemic drug between 1996 and 2002 and continued use of that drug for at
      least 12 months without adding other therapies. Change in weight was calculated
      as the annualized difference between baseline and follow-up weight and was
      adjusted for demographic and clinical characteristics. We then compared the
      weight changes observed in patients newly initiating SU, metformin, insulin and
      TZD therapies. RESULTS: After adjustment for demographic and clinical
      characteristics that might affect weight change, metformin initiators lost an
      average of 2.4 kg while all other groups gained weight. SU initiators gained the
      least (1.8 kg), followed by insulin initiators (3.3 kg) and TZD subjects (5.0
      kg). All comparisons were highly statistically significant. CONCLUSIONS: In an
      observational study of 1-year weight changes following the initiation of SUs,
      metformin, insulin or TZDs, we found similar but somewhat smaller weight changes
      than those previously reported in clinical trials. Our observed weight changes
      could not be explained by the many other factors we tested and seemed to apply
      across the full spectrum of diabetes patients. Our report provides valuable
      information that will allow the patient and clinician to anticipate, and perhaps
      address, expected weight changes that accompany the initiation of anti
      hyperglycaemic drugs.

PMID- 17199726
TI  - Effects of S 15511, a therapeutic metabolite of the insulin-sensitizing agent S
      15261, in the Zucker Diabetic Fatty rat.
AB  - AIM: S 15261 is a novel oral antihyperglycaemic drug with both insulin
      secretagogue and insulin-sensitizing effects. The study was designed to determine
      the biological activity of its two major metabolites, S 15511 and Y 415, and
      whether or not they have an additive effect. METHODS: Zucker Diabetic Fatty rats
      were treated for 28 days with S 15511 (10 mg/kg), Y 415 (10 mg/kg), or a
      combination at the same doses for a period of 4 weeks starting at 6-7 weeks of
      age. An additional group was pair-fed to the level of S 15511-treated animals to
      determine if possible effects were due to reduced food intake. RESULTS: S 15511
      alone and combined with Y 415 reduced energy intake and weight gain (-13% vs.
      controls; both p < 0.01). Baseline fasting plasma glucose levels were maintained
      by S 15511, S 15511 + Y 415 and pair-feeding (p < 0.01) for the entire treatment
      period (p < 0.01). Baseline insulin was maintained by pair-feeding only, whereas
      all other treated groups became hyperinsulinaemic (+110-276%; p < 0.05).
      Deterioration in insulin sensitivity [homeostasis model assessment (HOMA)-IR: +
      239%; p < 0.01] was attenuated by S 15511, S 15511 + Y 415 and pair-feeding (p <
      0.01) and was compensated for by improved insulin secretion (HOMA-beta; p <
      0.01). Oral glucose tolerance tests, performed on days 0, 14 and 28, showed that
      all groups had an impaired insulin response, but by day 28, S 15511, S 15511 + Y
      415 and pair-feeding had improved glucose disposal compared to the progressive
      deterioration in untreated controls (-44% to -48% vs. controls; p < 0.01),
      associated with progression to frank diabetes in these animals. CONCLUSION:
      Treatment with these agents in a genetic model of type 2 diabetes reveals that
      they all have a transient effect compared to the progressive worsening of vehicle
      treated controls. The improvements in glucose metabolism observed with S 15511
      are significant, however, suggesting it has more therapeutic activity than the Y
      415 metabolite of S 15261. It is associated with less frequent progression to
      diabetes; i.e. Y 415 exerts a non-significant effect alone and no significant
      additive effect when combined with S 15511. The mechanism of action of S 15511
      may be via increased insulin sensitivity and beta-cell response preservation up
      to day 21. Thus, previously reported insulin secretagogue effects are likely to
      be attributable to the parent compound.

PMID- 17199725
TI  - Insulin therapy in type 2 diabetes patients failing oral agents: cost
      effectiveness of biphasic insulin aspart 70/30 vs. insulin glargine in the US.
AB  - OBJECTIVES: To project the long-term clinical and economic outcomes of treatment
      with biphasic insulin aspart 30 (BIAsp 70/30, 30% soluble and 70% protaminated
      insulin aspart) vs. insulin glargine in insulin-naive type 2 diabetes patients
      failing to achieve glycemic control with oral antidiabetic agents alone (OADs).
      METHODS: Baseline patient characteristics and treatment effect data from the
      recent 'INITIATE' clinical trial served as input to a peer-reviewed, validated
      Markov/Monte-Carlo simulation model. INITIATE demonstrated improvements in HbA1c
      favouring BIAsp 70/30 vs. glargine (-0.43%; p < 0.005) and greater efficacy in
      reaching glycaemic targets among patients poorly controlled on OAD therapy.
      Effects on life expectancy (LE), quality-adjusted life expectancy (QALE),
      cumulative incidence of diabetes-related complications and direct medical costs
      (2004 USD) were projected over 35 years. Clinical outcomes and costs were
      discounted at a rate of 3.0% per annum. Sensitivity analyses were performed.
      RESULTS: Improvements in glycaemic control were projected to lead to gains in LE
      (0.19 +/- 0.24 years) and QALE (0.19 +/- 0.17 years) favouring BIAsp 70/30 vs.
      glargine. Treatment with BIAsp 70/30 was also associated with reductions in the
      cumulative incidences of diabetes-related complications, notably in renal and
      retinal conditions. The incremental cost-effectiveness ratio was $46 533 per
      quality-adjusted life year gained with BIAsp 70/30 vs. glargine (for patients
      with baseline HbA1c >/= 8.5%, it was $34 916). Total lifetime costs were compared
      to efficacy rates in both arms as a ratio, which revealed that the lifetime cost
      per patient treated successfully to target HbA1c levels of <7.0% and </= 6.5%
      were $80 523 and $93 242 lower with BIAsp 70/30 than with glargine, respectively.
      CONCLUSIONS: Long-term treatment with BIAsp 70/30 was projected to be cost
      effective for patients with type 2 diabetes insufficiently controlled on OADs
      alone compared to glargine. Treatment with BIAsp 70/30 was estimated to represent
      an appropriate investment of healthcare dollars in the management of type 2
      diabetes.

PMID- 17199727
TI  - Implications of hyperglycaemia and ethnicity in patients with acute coronary
      syndromes in New Zealand.
AB  - BACKGROUND: Admission blood glucose (ABG) is an independent predictor of death in
      patients with acute ST elevation myocardial infarction (STEMI). In New Zealand,
      mortality following myocardial infarction is disproportionally higher in Maori.
      Little information, however, exists concerning the predictive value of ABG in non
      ST elevation acute coronary syndromes (NSTEACS) events or indeed if similar
      ethnic differences exist in outcome in this patient population. AIM: To assess
      the predictive value of ABG and ethnicity in individuals admitted with acute
      coronary syndromes (ACS) on mortality. METHODS: A retrospective analysis of
      hospital discharge diagnosis of all ACS between 1 January 1999 and 31 December
      2002 at Waikato hospital, Hamilton, New Zealand. The primary outcome was all
      cause mortality. RESULTS: There were 4408 episodes of ACS with 1091 (25%) due to
      STEMI. There were 806 (18%) deaths. The presence of diabetes mellitus (DM) or an
      elevated ABG, in the absence of a history of DM, was associated with poor patient
      outcome. Early mortality is seen in individuals presenting with STEMI. People in
      the highest glucose category were older, more likely to be Maori, had a higher
      percentage of people with diabetes and remained in hospital longer, regardless of
      ACS type, than those in the lowest glucose category. Diabetes was more common in
      Maori (33%) than in Europeans (17.5%); p < 0.001. Significant risk factors for
      mortality were age, gender, diabetes, ethnicity, glucose and STEMI. For each
      mmol/l increase in glucose there is a 4.3% increase risk of dying. Adjusting for
      age and gender, Maori have a much higher mortality than Europeans (RR 2.12; p <
      0.00001) regardless of ACS type (STEMI or NSTEACS). CONCLUSIONS: Our study
      confirms the higher mortality following ACS, of Maori compared to New Zealanders
      of European origin. A raised ABG is a marker of this increased risk in all
      patients with ACS.

PMID- 17199728
TI  - Beneficial effects of gliclazide modified release compared with glibenclamide on
      endothelial activation and low-grade inflammation in patients with type 2
      diabetes.

PMID- 17199729
TI  - European differences in the association between the UCP2 -866G > A common gene
      variant and markers of body mass and fasting plasma insulin.

PMID- 17199730
TI  - The IRIS III study: pioglitazone improves metabolic control and blood pressure in
      patients with type 2 diabetes without increasing body weight.

PMID- 17199731
TI  - The 4G/4G PAI-1 genotype is associated with elevated plasma PAI-1 levels
      regardless of variables of the metabolic syndrome and smoking status. A
      population-based study in Spanish population.
AB  - Reported data about the effect of the 4G/5G PAI-1 polymorphism on plasma PAI-1
      levels are controversial. This study was designed to determine the relative
      effect of the 4G/5G PAI-1 polymorphism on high plasma PAI-1 levels after
      adjustment for metabolic syndrome - related variables, and to test if this effect
      is modified by the smoking status. Six hundred and thirty one unrelated subjects
      (292 men; 35-74 years), from a cross-sectional population-based epidemiological
      survey in the province of Segovia (Spain) were studied. The higher frequency of
      high PAI-1 levels was found in 4G/4G subjects (5G/5G 19.4%, 4G/5G 21.6%, 4G/4G
      33.7%, p = 0.003). A multiple regression model, adjusted for gender, age, BMI,
      waist circumference, triglycerides, HDL-cholesterol, HOMA IR and leptin, showed
      this adjOR: 4G/4G vs 5G/5G: 2.22, p = 0.008. When smoking status - 4G/5G PAI-1
      interaction was included as an independent variable these results were not
      modified. Our results indicate that the 4G/4G PAI-1 genotype might be strongly
      associated with high PAI-1 levels regardless of metabolic syndrome-related
      variables and smoking status.

PMID- 17199732
TI  - Pharmacological inhibition of TRalpha1 receptor potentiates the thyroxine effect
      on body weight reduction in rats: potential therapeutic implications in
      controlling body weight.
AB  - It has been previously reported that thyroid hormone receptor alpha1 (TRalpha1)
      is involved in the regulation of food intake and heart rhythm. Herein, we show
      that pharmacological inhibition of TRalpha1 by dronedarone, an amiodarone like
      compound (shown to antagonize thyroid hormone binding to TRalpha1), prevented the
      thyroid hormone induced increase in food intake and heart rate acceleration in
      rats. This resulted in a marked reduction in body weight. It is likely that
      thyroid analogs may prove potential therapeutic agents for controlling body
      weight.

PMID- 17199733
TI  - Metabolism of high density lipoprotein apolipoprotein A-I and cholesteryl ester
      in insulin resistant dog: a stable isotope study.
AB  - AIMS: In reverse cholesterol transport (RCT), hepatic Scavenger Receptor class B
      type I (SR-BI) plays an important role by mediating the selective uptake of high
      density lipoprotein cholesteryl ester (HDL-CE). However, little is known about
      this antiatherogenic mechanism in insulin resistance. HDL-CE selective uptake
      represents the main process for HDL-CE turnover in dog, a species lacking
      cholesteryl ester transfer protein activity. We therefore investigate the effects
      of diet induced insulin resistance on RCT. METHODS: Five beagle dogs, in healthy
      and insulin resistant states, underwent a primed constant infusion of
      [1,2(13)C(2)]acetate and [5,5,5-(2)H(3)]leucine, as labelled precursors of CE and
      apolipoprotein (apo) A-I, respectively. Data were analysed using modelling
      methods. RESULTS: HDL-apo A-I concentration did not change in insulin resistant
      state but apo A-I absolute production rate (APR) and fractional catabolic rate
      (FCR) were both higher (2.2- and 2.4-fold, respectively, p < 0.05). HDL-CE levels
      were lower (1.2-fold, p < 0.05). HDL-CE APR and FCR were both lower (2.3- and 2
      fold, respectively, p < 0.05), as well as selective uptake (2.6-fold, p < 0.05).
      CONCLUSIONS: Lower HDL-CE selective uptake suggests that RCT is impaired in obese
      insulin resistant dog.

PMID- 17199734
TI  - The addition of metformin in type 1 diabetes improves insulin sensitivity,
      diabetic control, body composition and patient well-being.
AB  - AIM: As many overweight people with T1DM are insulin resistant, adjuvant therapy
      with insulin sensitising agents, such as metformin, may be beneficial. This study
      evaluated the effect of adjuvant metformin in T1DM on insulin sensitivity,
      diabetic control, body composition, quality of life (QOL) and treatment
      satisfaction. MATERIALS AND METHODS: A 3-month prospective open-labelled pilot
      study of 16 patients aged 18-40 with T1DM and body mass index (BMI) >25 kg/m(2)
      was performed. The patients received 500-850 mg metformin twice daily. Insulin
      sensitivity, assessed by a frequently sampled intravenous glucose tolerance test
      [n=5], body composition, HbA(1c) and quality of life (QOL) were measured before
      and after treatment. A retrospective review of 30 patients with T1DM treated with
      metformin for at least 4 months was also performed. BMI, HbA(1c) and insulin
      requirements during metformin treatment was compared to pre-metformin data, and
      to patients treated with insulin only. RESULTS: In the pilot study, insulin
      sensitivity increased significantly from 0.86 +/- 0.33 x 10(-4)/min/(microU/ml)
      to 1.17 +/- 0.48 x 10(-4)/min/(microU/ml) after 3 months adjuvant therapy (p =
      0.043). This was associated with a decreased insulin requirement and mean daily
      blood glucose. There were no significant changes in HbA(1c) or body composition.
      QOL significantly improved (p < 0.002). The retrospective review revealed an
      initial reduction in HbA(1c) (0.8 +/- 1.4%, p = 0.001). This effect diminished
      with prolonged treatment. BMI decreased in patients remaining on metformin for a
      2-year period (0.5 +/- 0.5kg/m(2), p = 0.042). CONCLUSION: Adjuvant metformin can
      improve QOL, insulin sensitivity and glycaemic control in overweight adults with
      T1DM.

PMID- 17199735
TI  - Use of repaglinide on a pregnant woman during embryogenesis.
AB  - In the past few years, oral antihyperglycaemic agents have been considered as an
      alternative to insulin therapy in the treatment of gestational diabetes. There is
      still little information available on the safety of these drugs during pregnancy,
      but there have been several studies published regarding their use. Here we report
      on the case of a woman who took repaglinide up to the seventh week of pregnancy.
      Delivery occured with no complications and the newborn showed no malformations.
      Further studies are required to confirm the safety of repaglinide during
      pregnancy.

PMID- 17199736
TI  - Roles of the ribosomal protein S19 dimer and the C5a receptor in
      pathophysiological functions of phagocytic leukocytes.
AB  - Monocytes and neutrophils, the major phagocytic leukocytes, migrate to
      inflammatory sites by sensing chemoattractants such as anaphylatoxin C5a with
      membrane receptors such as C5a receptor. Upon stimulation, the leukocytes
      increase cytoplasmic Ca(2+) concentration and generate radical oxygen species.
      These leukocytes have different functions in inflammation. Neutrophils migrate
      more rapidly and induce vascular plasma leakage upon infiltration. Monocytes
      infiltrate tissue more slowly but have superior capacities of phagocytosis and
      antigen presentation. There must be mechanisms to separately recruit the
      leukocyte species at an inflammatory site. Ribosomal protein S19 (RP S19) is a
      component of ribosome. During apoptosis, RP S19 is dimerized and obtains a ligand
      capacity to C5a receptor. The RP S19 dimer attracts monocytes to phagocytically
      clear the apoptotic cells that released the dimer molecules. The phagocytic
      monocytes/macrophages then translocate to regional lymph nodes and present
      apoptotic cell-derived antigens. Oppositely, the RP S19 dimer inhibits C5a
      induced neutrophil migration and promotes apoptosis of neutrophils via the C5a
      receptor. The RP S19 dimer seems to prevent excessive tissue destruction induced
      by neutrophils. Skp is a molecular chaperon of Gram-negative bacteria. Skp also
      attracts monocytes and neutrophils as a ligand of C5a receptor. However, it
      promotes neither cytoplasmic Ca(2+) enhancement nor radical oxygen generation.

PMID- 17199738
TI  - Activated perilobular, not periacinar, pancreatic stellate cells contribute to
      fibrogenesis in chronic alcoholic pancreatitis.
AB  - The authors investigated the role of activated perilobular, not periacinar,
      pancreatic stellate cells, in fibrogenesis in chronic pancreatitis, based on the
      distribution of myofibroblasts. Twenty-four patients with clinically diagnosed
      chronic alcoholic pancreatitis were studied histopathologically,
      immunohistochemically and quantitatively. In all cases, fibrosis was patchily
      distributed in the perilobular, or interlobular, areas, accompanied by a
      cirrhosis-like appearance; it had extended into the intralobular area in advanced
      cases. Seven patients had a massive or confluent loss of exocrine tissue,
      resulting in extensive interlobular fibrosis; the more extensive the interlobular
      fibrosis, the smaller the lobules. Immunoreactivity to alpha-smooth muscle actin,
      a myofibroblast marker, was found mostly in the same areas of the fibrosis,
      mainly the interlobular, and less often the periacinar, areas; the average
      percentage area of perilobular myofibroblasts was significantly higher than that
      of periacinar myofibroblasts in 20 randomly selected lobules (P > 0.001), in
      which the average value for the former was 38.03% (range: 13.54-61.32%; SD,
      13.8%) and that for the latter was 4.85% (range 0.90-9.57%; SD, 2.22%). Fibrosis
      also immunostained positive for collagen types I and III. In conclusion,
      activated perilobular, not periacinar, pancreatic stellate cell contribute to
      fibrogenesis in chronic pancreatitis.

PMID- 17199737
TI  - Lack of association between BRAF V600E mutation and mitogen-activated protein
      kinase activation in papillary thyroid carcinoma.
AB  - The BRAF V600E mutation has been identified in a high proportion of papillary
      thyroid carcinoma (PTC). In cell lines and a transgenic mouse model it has been
      demonstrated that the mutation constitutively activates the mitogen-activated
      protein kinase (MAPK) pathway but in human PTC samples its effects remain
      unexamined. Herein the correlation of BRAF mutation and MAPK activation was
      examined in 42 human PTC samples. Activating mutations of the BRAF gene and all
      three RAS genes were detected by polymerase chain reaction-direct sequencing, and
      RET/PTC1 rearrangements were screened by nested reverse transcription-polymerase
      chain reaction. MAPK activation was assessed by immunohistochemistry and western
      blot analysis. Twenty-eight cases (66.7%) of BRAF V600E mutation, three cases
      (7.1%) of RET/PTC1 rearrangement but no cases of RAS genes mutation were
      identified. Activated MAPK was found in six cases (14.3%) with only two cases of
      mutant BRAF. In total 7.1% of PTC with BRAF mutation had activated MAPK.
      Furthermore, BRAF mutations were more prevalent in patients > or =45 years, but
      did not correlate with aggressive clinical behaviors. Absence of association
      between BRAF mutation and activation of MAPK pathway in PTC suggests the presence
      of mechanisms that downregulate MAPK activation.

PMID- 17199739
TI  - Angiomatous spindle cell lipoma: Report of three cases with immunohistochemical
      and ultrastructural study and reappraisal of former 'pseudoangiomatous' variant.
AB  - Pseudoangiomatous spindle cell lipoma (PASCL) is a rare variant of spindle cell
      lipoma that is composed of spindle fibroblast-like cells and mature adipose
      cells, and that is further characterized by intratumoral branching spaces
      regarded originally to be non-vascular (hence the adjective 'pseudoangiomatous').
      Reported herein are three cases of this tumor, with literature review of all six
      cases described previously. PASCL appears to have clinical features (age, sex,
      location, prognosis) similar to those of conventional spindle cell lipoma (SCL).
      Immunohistochemically, the spindle cells in all of the present cases were
      positive for CD34, as in conventional SCL. All lesions had at least mild
      positivity for sex steroid hormone receptors. The cells lining intratumoral
      dilated and branching spaces typical of this variant were strongly positive for
      lymphatic endothelial marker D2-40 in all cases, and for vascular markers CD31
      and F-VIII in one case. Ultrastructural study confirmed the endothelial nature of
      these cells. The results indicate that pseudoangiomatous SCL is truly angiomatous
      and should be termed as such. It could represent a sex steroid hormone-dependent
      lesion.

PMID- 17199740
TI  - Autopsy case of desminopathy involving skeletal and cardiac muscle.
AB  - Desminopathy is a familial or sporadic skeletal and cardiac muscular dystrophy
      caused by mutation in the desmin gene. Desmin-reactive deposits in the affected
      muscles are the morphological hallmarks of this disease. Herein is reported an
      autopsy case of a 57-year-old Japanese man with adult-onset skeletal muscle
      weakness and atrioventricular (A-V) conducting block, with a missense A337P
      mutation in exon 5 of the desmin gene. Disease onset occurred when the patient
      was 45 years old. The initial presentation was lower limb weakness, and the
      weakness progressed to the upper limbs. When the patient was 51 years old, a
      cardiac pacemaker was implanted due to complete A-V block. When the patient was
      53 years old, respiratory insufficiency occurred due to weakness of respiratory
      muscles, and the patient died at the age of 57 years. On autopsy,
      intrasarcoplasmic desmin-immunoreactive deposits were identified in the skeletal
      and cardiac muscle, and abnormal accumulations of granulofilamentous material
      were identified at the ultrastructural level. In the cardiac conducting system,
      calcification was observed at the bundle of His, and sporadic calcium deposits
      were observed at the left and right bundle branches.

PMID- 17199741
TI  - Trisomy 10p and translocation of 10q to 4p associated with selective dysgenesis
      of IgA-producing cells in lymphoid tissue.
AB  - A combined chromosomal abberation trisomy of the short arm of chromosome 10
      associated with translocation of 10q to chromosome 4p was found in a 14-month-old
      boy, who died after repeated bouts of pneumonia. The translocation involved the
      target region 4p16.3 of Wolf-Hirschhorn syndrome and/or Pitt-Rogers-Danks
      syndrome. The karyotype was 46,XY,der(4)t(4;10)(p16;q11.2),i(10)(p10),ish
      der(4)t(4;10)(p16.3;q11.2) (D4S96+,D4Z1+),i(10) (pter ++). In addition to growth
      retardation and external as well as internal dysmorphism, the patient had
      abnormalities of the immune system, such as thymic involution, generalized lymph
      node enlargement, unusual distribution of T cells in lymphoid follicles, and
      selective IgA deficiency. The IgA-producing cells were rarely found in lymph
      nodes but normally in intestinal mucosa. In contrast, in the lymph nodes, the
      paracortical T-lymphocytes were hyperplastic, but they rarely entered the primary
      follicles. It is assumed that the chromosomal abnormality may lead to the
      dysfunction of T lymphocytes and, further, to the dysgenesis of IgA-producing
      cells in lymph nodes but not in intestinal mucosa. This suggests that the thymus
      may differentially control the subsets of IgA-producing cells in lymph nodes and
      intestinal mucosa.

PMID- 17199742
TI  - Pure acinic cell carcinoma of the breast in an 80-year-old Japanese woman.
AB  - Acinic cell carcinoma of the breast is an uncommon neoplasm. Since the first case
      of this rare variant of breast carcinoma was reported in 1996, only 10 cases have
      been reported in the English-language literature. Reported herein is the first
      case of primary acinic cell carcinoma of the breast in a Japanese woman. To the
      naked eye, the tumor appeared well circumscribed and the cut surface was grayish
      pink and hemorrhaging. Microscopically, the tumor was predominantly made up of a
      monotonous proliferation of cells with a finely granular cytoplasm, resembling
      acinic cells of the parotid gland. Some neoplastic cells had a clear cytoplasm.
      In spite of extensive sampling, no common histological patterns of breast
      carcinoma such as in situ and invasive ductal carcinoma were recognized in the
      present case, indicating that the present case was pure acinic cell carcinoma. In
      addition, the immunohistochemical profile of this tumor was identical to that of
      the acinic cell carcinoma of the salivary gland: estrogen receptor, progesterone
      receptor, HER2 and cytokeratin (CK)20 were negative and amylase and CK7 were
      positive. The patient has been well for 22 months since the wide local excision
      of the tumor and no signs of salivary neoplasm are evident to date.

PMID- 17199745
TI  - Polymorphism of the ITS-2 region of the ribosomal DNA of the Triatominae Rhodnius
      domesticus, R. pictipes, R. prolixus and R. stali.
AB  - The polymerase chain reaction-restriction fragment length polymorphism technique
      (PCR-RFLP) was used to compare Rhodnius domesticus (Neiva & Pinto), R. pictipes
      (Stal), R. prolixus (Stal) and R. stali (Lent, Jurberg & Galvao) (Hemiptera:
      Reduviidae). The enzyme BstUI differentiated R. domesticus, R. pictipes and R.
      prolixus, and HhaI differentiated R. domesticus, R. pictipes and R. stali. With
      the fingerprinting analysis generated by these two enzymes, it was possible to
      clearly identify all four species in the study.

PMID- 17199743
TI  - MALT1, BCL10 and FOXP1 in salivary gland mucosa-associated lymphoid tissue
      lymphomas.
AB  - In view of the certain anatomic site-dependent frequency of chromosomal
      translocations involved in extranodal marginal zone B cell lymphoma of mucosa
      associated lymphoid tissue (MALT lymphoma) pathogenesis, 17 salivary gland MALT
      lymphoma cases were analyzed for MALT1 and FOXP1 translocations. B cell
      CLL/lymphoma 10 (BCL10) and forkhead box PA (FOXP1) protein expression were
      studied by immunohistochemistry and translocations identified using fluorescence
      in situ hybridization (FISH)-specific probes FOXP1, t(11;18)(q21;q21)/API2-MALT1
      and t(14;18)(q32;q21)/IgH-MALT1. None of the 11 analyzed cases showed FOXP1
      rearrangement or amplification. The t(11;18) was present in five of 13 cases and
      the t(14;18) in three of 13 cases. MALT1 translocations were mostly mutually
      exclusive except in a single case. FOXP1 protein expression showed differences in
      the proportion of tumor cells with nuclear expression but not in their intensity,
      with the exception of one case where very intense nuclear staining was noted.
      BCL10 nuclear expression was present in four of 17 cases, two of which lacked
      t(11;18). Our results suggest that MALT1-specific translocations and FOXP1
      rearrangements are not commonly involved in pathogenesis. A case with strong
      FOXP1 protein expression indicates the possibility that the upregulation of FOXP1
      expression is significant in a small subset of salivary gland MALT lymphomas.
      Also a single case in which both MALT1 translocations were present indicates that
      these are not always mutually exclusive.

PMID- 17199746
TI  - The zoophilic fruitfly Phortica variegata: morphology, ecology and biological
      niche.
AB  - Flies belonging to the subfamily Steganinae (Drosophilidae) display unusual
      zoophilic feeding habits at the adult and/or larval stage. Phortica variegata
      (Fallen) feeds on tears or eye liquid around the eyes of humans and carnivores.
      When feeding it is a potential vector of Thelazia callipaeda (Railliet and Henry)
      eyeworms. Adult and larval stages of this fly may be easily confused with other
      species belonging to the same genus, and little is known on the biology and
      ecology of P. variegata. In April-November 2005, a total of 969 P. variegata were
      collected in an area with a high prevalence of canine thelaziosis. The number of
      flies collected weekly was then related to climatic and environmental parameters
      (e.g. temperature, relative humidity and total rainfall) recorded daily at the
      collection site. The highest number of Phortica were collected during July
      August. The sex ratio (number of males : females) rose from approximately 0.5
      during May-July, to approximately 3.0 in August and 181 during September-October.
      Distributional data, representing 242 sites at which P. variegata has been
      collected in Europe, were analysed using a desktop implementation of the genetic
      algorithm for rule-set prediction (GARP) to model ecological requirements across
      Europe, as well as in Italy. P. variegata is shown to be mainly active at 20-25
      degrees C and 50-75% RH. The ecological niche model suggests with a high degree
      of confidence that large areas of Europe are likely to represent suitable habitat
      for this species, mostly concentrated in central Europe. The results reported
      here contribute basic knowledge on the ecology and geographical distribution of
      P. variegata flies, which will be fundamental to gaining a better understanding
      of their role as vectors of human and animal pathogens.

PMID- 17199747
TI  - Developmental profiles in tick water balance with a focus on the new Rocky
      Mountain spotted fever vector, Rhipicephalus sanguineus.
AB  - Recent reports indicate that the common brown dog tick, or kennel tick,
      Rhipicephalus sanguineus (Latreille) (Acari: Ixodidae) is a competent vector of
      Rocky Mountain spotted fever in the U.S.A. This tick is of concern to public
      health because of its high frequency of contact, as it has a unique ability to
      thrive within human homes. To assess the moisture requirements necessary for
      survival, water balance characteristics were determined for each developmental
      stage, from egg to adult. This is the first time that water relations in ticks
      have been assessed throughout the complete lifecycle. Notably, R. sanguineus is
      differentially adapted for life in a dry environment, as characterized by a
      suppressed water loss rate distinctive for each stage that distinguishes it from
      other ticks. Analysis of its dehydration tolerance limit and percentage body
      water content provides no evidence to suggest that the various stages of this
      tick can function more effectively containing less water, indicating that this
      species is modified for water conservation, not desiccation hardiness. All
      stages, eggs excepted, absorb water vapour from the air and can drink free water
      to replenish water stores. Developmentally, a shift in water balance strategies
      occurs in the transition from the larva, where the emphasis is on water gain
      (water vapour absorption from drier air), to the adult, where the emphasis is on
      water retention (low water loss rate). These results on the xerophilic-nature of
      R. sanguineus identify overhydration as the primary water stress, indicating that
      this tick is less dependent upon a moisture-rich habitat for survival, which
      matches its preference for a dry environment. We suggest that the controlled,
      host-confined conditions of homes and kennels have played a key role in promoting
      the ubiquitous distribution of R. sanguineus by creating isolated arid
      environments that enable this tick to establish within regions that are
      unfavourable for maintaining water balance.

PMID- 17199748
TI  - The effect of repellents Ocimum forskolei and deet on the response of Anopheles
      stephensi to host odours.
AB  - The behavioural response of Anopheles stephensi Liston (Diptera: Culicidae) to
      incubated host odours (from human and goat) and to human odour in combination
      with a repellent plant, Ocimum forskolei (Labiatae), or deet (N, N, diethyl
      toluamide) (20%) was tested in a dual-port olfactometer. An. stephensi was
      significantly attracted to both host odours compared with air alone, but showed
      no preference when given a choice between both host odours simultaneously. In
      choice tests, the addition of deet to human odour did not significantly divert
      mosquitoes to human odour alone, but did divert them to goat odour. O. forskolei
      combined with human odour diverted mosquitoes to goat or human odour alone.
      Combinations of human odour and O. forskolei, and human odour and deet were both
      as unattractive as air alone, and attracted mosquitoes equally when offered
      simultaneously. The results indicate that use of O. forskolei as a repellent
      would be beneficial in reducing vector biting if used in communities in areas
      with partially zoophilic mosquito species such as An. stephensi, and where
      animals are present.

PMID- 17199749
TI  - Effect of Novaluron (Rimon 10 EC) on the mosquitoes Anopheles albimanus,
      Anopheles pseudopunctipennis, Aedes aegypti, Aedes albopictus and Culex
      quinquefasciatus from Chiapas, Mexico.
AB  - Dengue fever is a serious problem in Mexico and vector control has not been
      effective enough at preventing outbreaks. Malaria is largely under control, but
      it is important that new control measures continue to be developed. Novaluron, a
      novel host-specific insect growth regulator and chitin synthesis inhibitor, has
      proved to be effective against agricultural pests, but its efficacy against
      larval mosquito vectors under field conditions remains unknown. In accordance
      with the World Health Organization Pesticide Evaluation Scheme, phase I, II and
      III studies were conducted to evaluate the efficacy and residual effect of
      Novaluron (Rimon 10 EC, Makhteshim, Beer-Sheva, Israel) on the malaria vectors
      Anopheles albimanus Wiedemann (Diptera: Culicidae) and Anopheles
      pseudopunctipennis Theobald, the dengue vectors Aedes aegypti (L) and Aedes
      albopictus Skuse and the nuisance mosquito Culex quinquefasciatus Say. Laboratory
      susceptibility tests yielded diagnostic concentrations for all five target
      species. Field trials to identify the optimum field dosage of Novaluron against
      Anopheles mosquitoes were carried out under semi-natural conditions in artificial
      plots and in vessels with wild mosquitoes. Efficacy was measured by monitoring
      mortality of larvae and pupae and the percentage of inhibition of emergence from
      floating cages. Dosages of Novaluron for field tests were based on pupal LC(99)
      (lethal concentration 99%) of An. pseudopunctipennis (0.166 mg/L) in plots and
      average pupal LC(99) of Ae. aegypti and Ae. albopictus (0.55 mg/L). At all
      dosages tested, Novaluron significantly reduced larval populations of An.
      albimanus, Culex coronator Dyar & Knab, Ae. albopictus and Cx. quinquefasciatus
      by approximately 90%, inhibited adult emergence of An. albimanus and An.
      pseudopunctipennis by approximately 97% for almost 4 months in experimental
      plots, and inhibited adult emergence of Ae. aegypti and Ae. albopictus by
      approximately 97% for up to 14 weeks. Recommended dosages of Novaluron for non
      container breeding and container breeding mosquitoes are 0.166 mg/L and 0.55
      mg/L, respectively. Overall, the residual effect was more sustained than that of
      temephos. The lowest dosage of Novaluron had less of an impact on non-target
      organisms than did temephos. Small-scale field trials in natural breeding sites
      treated with Novaluron at 0.6 L/ha eliminated adult emergence of An. albimanus
      and Cx. coronator for 8 weeks. For phase III studies, Novaluron was tested at the
      local and village levels, applying the optimum field rate to all natural breeding
      habitats within 1 km of a pair of neighbouring villages. Village-scale trials of
      Novaluron at 0.6 L/ha reduced An. albimanus larval populations for at least 8
      weeks and, more importantly, sharply reduced the densities of adult host-seeking
      mosquitoes approaching houses. We conclude that Novaluron is effective and
      environmentally safer than temephos.

PMID- 17199750
TI  - The effect of starvation on the susceptibility of teneral and non-teneral tsetse
      flies to trypanosome infection.
AB  - Transmission of vector-borne diseases depends largely on the ability of the
      insect vector to become infected with the parasite. In tsetse flies, newly
      emerged or teneral flies are considered the most likely to develop a mature,
      infective trypanosome infection. This was confirmed during experimental
      infections where laboratory-reared Glossina morsitans morsitans Westwood
      (Diptera: Glossinidae) were infected with Trypanosoma congolense or T. brucei
      brucei. The ability of mature adult tsetse flies to become infected with
      trypanosomes was significantly lower than that of newly emerged flies for both
      parasites. However, the nutritional status of the tsetse at the time of the
      infective bloodmeal affected its ability to acquire either a T. congolense or T.
      b. brucei infection. Indeed, an extreme period of starvation (3-4 days for
      teneral flies, 7 days for adult flies) lowers the developmental barrier for a
      trypanosome infection, especially at the midgut level of the tsetse fly. Adult G.
      m. morsitans became at least as susceptible as newly emerged flies to infection
      with T. congolense. Moreover, the susceptibility of adult flies, starved for 7
      days, to an infection with T. b. brucei was also significantly increased, but
      only at the level of maturation of an established midgut infection to a salivary
      gland infection. The outcome of these experimental infections clearly suggests
      that, under natural conditions, nutritional stress in adult tsetse flies could
      contribute substantially to the epidemiology of tsetse-transmitted
      trypanosomiasis.

PMID- 17199751
TI  - Population structure of an island malaria vector.
AB  - The impact of islands on the population structure of Anopheles flavirostris
      (Ludlow) (Diptera: Culicidae), the primary malaria vector in the Philippines, was
      assessed. A phylogenetic analysis of 16 cytochrome oxidase subunit 1 (CO1)
      haplotypes revealed three clades: one basal clade containing genetically
      disparate haplotypes from Mindanao, and two derived clades, one of which was
      largely confined to the largest island, Luzon, and one that was widespread except
      for Luzon. For the Luzon clade, nested clade analysis revealed an isolation-by
      distance effect, and a mismatch distribution analysis diagnosed a recent
      demographic expansion (sum of squared deviation, SDD = 0.0093, P= 0.075), which
      mirrors demographic attributes found in mainland primary malaria vectors and
      could inflate estimates of gene flow from F(ST). For the widespread clade,
      evidence of range expansion and past fragmentation and/or long distance
      colonization from the Visayas or Mindanao to Palawan is suggested. A south-to
      north range expansion of An. flavirostris is suggested; estimates of coalescence
      for the Luzon clade was 214 000 years ago (ya) (95% confidence interval 35 600
      298 000 ya), i.e. late Pleistocene. Present day rather than Pleistocene island
      association and some, but not all, sea barriers appeared to be important for An.
      flavirostris population structure. Our results suggest that endemic island
      malaria vector species need to be considered before any generalizations are made
      about the population structure of primary and secondary vectors.

PMID- 17199752
TI  - Footbath acaricide treatment to control cattle infestation by the tick Amblyomma
      variegatum.
AB  - Previous studies have shown that about 90% of adult Amblyomma variegatum
      Fabricius (Acari: Ixodidae) picked up daily by grazing cattle are still attached
      to the interdigital areas in the evening, when the animals return from pasture.
      It was therefore postulated that a targeted treatment, designed to kill the ticks
      attached to the feet, would limit infestation of the predilection sites.
      Footbaths filled with various pyrethroid formulations were used over 3 years, at
      the beginning of the rainy season (from mid-May to the end of July), to assess
      the efficacy of such a control method. It proved efficient in preventing the
      ticks from attaching to the predilection sites. Although five to 12 A. variegatum
      adults attached to each treated animal daily, and although the tick burden of the
      predilection sites of control cattle increased each day by four to 10 ticks, the
      average infestation of the predilection sites of treated cattle that were
      initially highly infested (over 100 ticks/animal) continuously decreased to reach
      a level of about 10-30 ticks/animal after 6-8 weeks of treatment. In herds with a
      lower initial tick burden (40-70 ticks/animal) this level was obtained within 2-3
      weeks and the mean infestation subsequently remained consistently low. Footbath
      treatment carried out every other day during the adult peak infestation period
      should therefore greatly limit losses due to ticks. This method was appreciated
      by traditional livestock farmers, essentially because it is not time-consuming
      and because it requires only c. 200 mL aqueous formulation per animal at each
      passage. The cost of the acaricide needed to treat one animal during the peak
      infestation period was assessed at c. euro 0.20. This control method might also
      have an impact on some species of tsetse flies and mosquitoes, thereby
      contributing to trypanosomiasis and malaria control.

PMID- 17199753
TI  - Identifying Canadian mosquito species through DNA barcodes.
AB  - A short fragment of mt DNA from the cytochrome c oxidase 1 (CO1) region was used
      to provide the first CO1 barcodes for 37 species of Canadian mosquitoes (Diptera:
      Culicidae) from the provinces Ontario and New Brunswick. Sequence variation was
      analysed in a 617-bp fragment from the 5' end of the CO1 region. Sequences of
      each mosquito species formed barcode clusters with tight cohesion that were
      usually clearly distinct from those of allied species. CO1 sequence divergences
      were, on average, nearly 20 times higher for congeneric species than for members
      of a species; divergences between congeneric species averaged 10.4% (range 0.2
      17.2%), whereas those for conspecific individuals averaged 0.5% (range 0.0-3.9%).

PMID- 17199754
TI  - Blood-feeding behaviour of the malarial mosquito Anopheles arabiensis:
      implications for vector control.
AB  - Feeding behaviour of the malaria vector Anopheles arabiensis Patton (Diptera:
      Culicidae) was monitored for 12 months (March 2003-February 2004) in the Konso
      District of southern Ethiopia (5 degrees 15'N, 37 degrees 28'E). More than 45 000
      An. arabiensis females were collected by host-baited sampling methods (light
      traps, human landing catches, cattle-baited traps) and from resting sites (huts
      and pit shelters). In the village of Fuchucha, where the ratio of cattle : humans
      was 0.6 : 1, 51% of outdoor-resting mosquitoes and 66% of those collected indoors
      had fed on humans, human baits outdoors caught > 2.5 times more mosquitoes than
      those indoors and the mean catch of mosquitoes from pit shelters was about five
      times that from huts. Overall, the vast majority of feeding and resting occurred
      outdoors. In the cattle camps of Konso, where humans slept outdoors close to
      their cattle, approximately 46% of resting mosquitoes collected outdoors had fed
      on humans despite the high cattle : human ratio (17 : 1). In both places,
      relatively high proportions of bloodmeals were mixed cow + human: 22-25% at
      Fuchucha and 37% in the cattle camps. Anthropophily was also gauged
      experimentally by comparing the numbers of mosquitoes caught in odour-baited
      entry traps baited with either human or cattle odour. The human-baited trap
      caught about five times as many mosquitoes as the cattle-baited one.
      Notwithstanding the potential pitfalls of using standard sampling devices to
      analyse mosquito behaviour, the results suggest that the An. arabiensis
      population is inherently anthropophagic, but this is counterbalanced by exophagic
      and postprandial exophilic tendencies. Consequently, the population feeds
      sufficiently on humans to transmit malaria (sporozoite rates: 0.3% for Plasmodium
      falciparum and 0.5% for P. vivax, by detection of circumsporozoite antigen) but
      also takes a high proportion of meals from non-human hosts, with 59-91% of
      resting mosquitoes containing blood from cattle. Hence, classical zooprophylaxis
      is unlikely to have a significant impact on the malaria vectorial capacity of An.
      arabiensis in Konso, whereas treating cattle with insecticide might do.

PMID- 17199755
TI  - Development changes of cuticular hydrocarbons in Chrysomya rufifacies larvae:
      potential for determining larval age.
AB  - Age determination is the basis of determining the postmortem interval using
      necrophagous fly larvae. To explore the potential of using cuticular hydrocarbons
      for determining the ages of fly larvae, changes of cuticular hydrocarbons in
      developing larvae of Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae)
      were investigated using gas chromatography with flame-ionization detection and
      gas chromatography-mass spectrometry. This study showed that the larvae produced
      cuticular hydrocarbons typical of insects. Most of the hydrocarbons identified
      were alkanes with the carbon chain length of 21-31, plus six kinds of alkenes.
      The hydrocarbon composition of the larvae correlated with age. The statistical
      results showed that simple peak ratios of n-C29 divided by another eight selected
      peaks increased significantly with age; their relationships with age could be
      modelled using exponential or power functions with R(2) close to or > 0.80. These
      results suggest that cuticular hydrocarbon composition is a useful indicator for
      determining the age of larval C. rufifacies, especially for post-feeding larvae,
      which are difficult to differentiate by morphology.

PMID- 17199756
TI  - Blowfly succession from possum (Trichosurus vulpecula) carrion in a sheep-farming
      zone.
AB  - The significance of brushtail possum, Trichosurus vulpecula Kerr (Diprotodontia:
      Phalangeridae) carcasses to the succession and production of Diptera species and
      its relevance to fly strike management in Tasmania, Australia was examined.
      Calliphora stygia (Fabricius), Lucilia sericata (Meigen) and Calliphora vicina
      Robineau-Desvoidy (Diptera: Calliphoridae) were found to be the most abundant and
      Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) always the least abundant (<
      1%) of the putative primary fly invading species to emerge. Carcasses that were
      left for up to 15 days in the field before being exposed to flies for 2 days also
      acted as breeding sites for large numbers of all primary fly species, with the
      exception of L. cuprina. Ordination analysis revealed no relationship between
      possum carcasses according to their length of exposure but did show significant
      negative associations between the number of putative secondary invaders
      (Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae), Chrysomya varipes
      (Macquart) (Diptera: Calliphoridae) and putative tertiary flies (Hydrotaea
      rostrata Robineau-Desvoidy (Diptera: Muscidae)) to the number of C. vicina or C.
      stygia to emerge. There was enormous variability in the numbers of
      secondary/tertiary fly species to emerge from carcasses (0-11 450) that
      negatively correlated with the proportion of all flies to emerge that were
      primary, and with the mean size of adult L. sericata. Although carcass
      temperatures, especially those with a large larval population, were elevated,
      this did not appear to result in significant pre-adult fly mortality. The most
      important primary fly strike species L. cuprina was only found in insignificant
      numbers, whereas three other members of the fly strike fauna C. stygia, L.
      sericata and Ch. rufifacies did use possum carrion as an important breeding
      resource, but left implications for fly strike management inconclusive.

PMID- 17199757
TI  - Lifetime reproductive output of Calliphora vicina and Lucilia sericata in outdoor
      caged and field populations; flight vs. egg production?
AB  - Females of the blowflies Calliphora vicina (Robineau-Desvoidy) and Lucilia
      sericata (Meigen) (Diptera: Calliphoridae) maintained in sheltered outdoor cages
      and supplied with excess food, oviposited later than would have been expected
      from the temperature-sum. The survival rates of the caged flies was high and the
      isolation of flies from predation, extreme temperatures and food shortages is
      likely to have contributed to this. Despite good survival rates, subsequent egg
      production over the greater part of the adult life span was reduced to
      approximately 24% for C. vicina and approximately 55% for L. sericata, of the
      potential expected from the published temperature-sums required for the
      maturation of successive egg batches. The data suggest that under field-cage
      conditions there is a considerable variation in egg development between
      individuals of the same age and that this variation should not be overlooked,
      since it may have significant implications in ecological and forensic
      investigations; however, the cause of this variability remains unclear. While
      lower than expected, the reproductive outputs recorded in the cages were
      nevertheless considerably greater than those that have been estimated for
      blowflies in the field and illustrate the potential for population increase in
      these species under favourable conditions. The possibility of a greater energy
      investment in flight activity relative to reproductive output in C. vicina
      compared to L. sericata is proposed.

PMID- 17199758
TI  - Feeding and indoor resting behaviour of the mosquito Anopheles longipalpis in an
      area of hyperendemic malaria transmission in southern Zambia.
AB  - Anopheles longipalpis (Theobald) (Diptera: Culicidae) is a predominantly
      zoophilic mosquito that has not been implicated in malaria transmission. However,
      this species was collected indoors with An. funestus s.l. in southern Zambia,
      where transmission of Plasmodium falciparum is hyperendemic, and we initially
      misidentified it morphologically and molecularly as An. funestus s.l. The indoor
      resting density and blood-feeding behaviour of An. longipalpis were investigated
      during the 2004-05 and 2005-06 transmission seasons in Mufwafwi village in
      southern Zambia. Numbers of endophilic An. longipalpis increased towards the end
      of the rainy season. Although specimens were collected during human landing
      catches, the feeding behaviour of An. longipalpis was significantly biased
      towards cattle (88.7%), with other bloodmeals originating from dogs, goats and
      chickens. None of the 177 specimens of An. longipalpis were infected with P.
      falciparum. These data are consistent with existing reports that An. longipalpis
      is not involved in malaria transmission. However, more extensive sampling is
      necessary. Importantly, the correct identification of An. longipalpis is crucial
      for malaria control programmes in areas where An. funestus s.l and An.
      longipalpis exist sympatrically so that scarce resources are not wasted on the
      control of a non-vector.

PMID- 17199759
TI  - Selective use of odour-baited, insecticide-treated targets to control tsetse
      flies Glossina austeni and G. brevipalpis in South Africa.
AB  - The effectiveness of odour-baited targets treated with 0.8% deltamethrin in
      controlling Glossina austeni Newstead and G. brevipalpis Newstead (Diptera:
      Glossinidae) was evaluated in Zululand, South Africa. Targets were initially
      deployed in the three habitat types (grassland, woodland and forest) of two
      adjacent areas at a density of four targets per km(2). One area functioned as the
      treatment block (c. 35 km(2)) and included the focus of the target deployment,
      and the second area functioned as a barrier block (c. 40 km(2)) against tsetse
      fly re-invasion from the untreated area to the south. After 8 months, targets
      were removed from open grassland in both areas and target density in wooded
      habitats and sand forest was increased to eight per km(2). Twelve months later,
      all targets were removed from the barrier block and used to increase target
      density in the wooded and sand forest habitats of the treatment block to 12 per
      km(2). This target density was maintained for 14 months. In the treatment area, a
      99% reduction in G. austeni females occurred after 13 months at a target density
      of eight per km(2) in wooded habitat; this was maintained for 22 months.
      Reduction in G. brevipalpis was less marked. The relatively poor reduction in G.
      brevipalpis is attributed to the high mobility of this species and its
      distribution throughout less wooded and more open habitats.

PMID- 17199761
TI  - Guest editorial: it takes a village to heal a wound.

PMID- 17199762
TI  - Negative-pressure wound therapy: a snapshot of the evidence.
AB  - Topical negative pressure (TNP) is a mode of therapy used to encourage wound
      healing. It can be used as a primary treatment for chronic/complex wounds or as
      an adjunct to surgery. Based on the evidence to date, the clinical effectiveness
      of negative-pressure therapy is still unclear. Although case reports and
      retrospective studies have demonstrated enhanced wound healing in acute/traumatic
      wounds, chronic wounds, infected wounds, wounds secondary to diabetes mellitus,
      sternal wounds and lower limb wounds, there are very few randomised controlled
      trials, with unclear results. The evidence is lacking for the use of TNP therapy
      for other indications to enhance wound healing such as patients with decubitus
      ulcers, diabetes and peripheral vascular disease and to improve skin graft take.
      There have been, as yet, no quality-of-life studies available for negative
      pressure therapy. Despite this, the usage of TNP has increased. This review
      provides an overview of clinical studies using TNP and proposes avenues for
      further research to elucidate the exact mechanism of TNP, in addition to large
      randomised controlled clinical trials of patients undergoing this therapy.

PMID- 17199763
TI  - The management of deep sternal wound infections using vacuum assisted closure
      (V.A.C.) therapy.
AB  - A group of international experts met in May 2006 to develop clinical guidelines
      on the practical application of vacuum assisted closure (V.A.C.)+ therapy in deep
      sternal wound infections. Group discussion and an anonymous interactive voting
      system were used to develop content. The recommendations are based on current
      evidence or, where this was not available, the majority consensus of the
      international group. The principles of treatment for deep sternal wound
      infections include early recognition and treatment of infection. V.A.C. therapy
      should be instigated early, following thorough wound irrigation and surgical
      debridement. V.A.C. therapy in deep sternal wound infections requires specialist
      surgical supervision and should only be undertaken by clinicians with adequate
      experience and training in the use of the technique.

PMID- 17199764
TI  - Silver dressings: their role in wound management.
AB  - Dressings have a part to play in the management of wounds; whether they are
      sutured or open, usually chronic wounds of many aetiologies which are healing by
      secondary intention. They traditionally provide a moist wound environment, but
      this property has been extended through simple to complex, active dressings which
      can handle excessive exudate, aid in debridement, and promote disorganised,
      stalled healing. The control of infection remains a major challenge.
      Inappropriate antibiotic use risks allergy, toxicity and most importantly
      resistance, which is much reduced by the use of topical antiseptics (such as
      povidone iodine and chlorhexidine). The definition of what is an antimicrobial
      and the recognition of infection has proven difficult. Although silver has been
      recognised for centuries to inhibit infection its use in wound care is relatively
      recent. Evidence of the efficacy of the growing number of silver dressings in
      clinical trials, judged by the criteria of the Cochrane Collaboration, is
      lacking, but there are good indications for the use of silver dressings, to
      remove or reduce an increasing bioburden in burns and open wounds healing by
      secondary intention, or to act as a barrier against cross contamination of
      resistant organisms such as MRSA. More laboratory, and clinical data in
      particular, are needed to prove the value of the many silver dressings which are
      now available. Some confusion persists over the measurement of toxicity and
      antibacterial activity but all dressings provide an antibacterial action,
      involving several methods of delivery. Nanocrystalline technology appears to give
      the highest, sustained release of silver to a wound without clear risk of
      toxicity.

PMID- 17199765
TI  - Reimbursement of dressings: a WUWHS statement.

PMID- 17199766
TI  - Does dermal thermometry predict clinical outcome in diabetic foot infection?
      Analysis of data from the SIDESTEP* trial.
AB  - The purpose of the study was to assess in patients with a diabetic foot infection
      (DFI), whether differences in skin temperature of the affected foot as compared
      to the corresponding site on the contralateral foot using dermal thermometry (DT)
      correlates with infection severity and clinical outcome. As part of the SIDESTEP
      DFI study, investigators took DT measurements at baseline and the discontinuation
      of intravenous therapy (DCIV) and performed a systematic evaluation of the
      infected limb to calculate a wound score. We compared the skin temperature
      differential between the limbs at the two assessments and determined the
      correlation between this value and surrogate markers of inflammation and the
      clinical response to treatment. Among patients enrolled in SIDESTEP, 332 were
      fully evaluable. The mean temperature differential between the limbs was 2.81 +/-
      5.75 degrees F at baseline and 2.43 +/- 4.84 degrees F at DCIV (mean change: 
      0.37; 95% confidence interval (CI): -0.98, 0.23; P= 0.225). Skin temperature
      differential at baseline did not correlate with white blood cell count, level of
      C-reactive protein or erythrocyte sedimentation rate or the infection severity
      score (r= 0.058, 0.148, -0.002, 0.067, respectively). We observed no overall
      trend between surface temperature differential at baseline and clinical outcome
      at DCIV, but patients with a skin temperature differential of > or =10 degrees F
      at baseline had a significantly lower clinical response than those whose
      differential was <10 degrees F (81.4% versus 94.3%; difference 12.9%; 95% CI:
      3.5, 27.3%, P= 0.007). While there was no overall relationship between skin
      temperature and poor clinical outcome, there may be a threshold effect in DT (<10
      degrees F versus >10 degrees F) between the limbs at baseline that predicts
      outcome of therapy.

PMID- 17199767
TI  - In vitro diffusion bed, 3-day repeat challenge 'capacity' test for antimicrobial
      wound dressings.
AB  - The aim of this study was to develop an in vitro wound infection model that
      allows the comparison of the bacterial kill rate of antimicrobial wound dressings
      over the course of 3 days, with renewed microbial challenges each day, under
      realistic wound-like conditions. A test bed model of a moderately exuding wound
      was constructed from a hydrogel containing releasable foetal calf serum (FCS),
      and cellulose discs dosed with test microbes (Methicillin-resistant
      Staphylococcus aureus and Pseudomonas aeruginosa) suspended in 50% FCS applied at
      the interface between the test dressing and the hydrogel test bed. Freshly
      prepared discs were used to challenge the same dressing over a 23-hour period for
      a course of 3 days. Different test dressings produced differing kill rates,
      allowing quantitative comparison of both their immediate activity and their
      capacity to continue working over 3 days, within a fluid-donating system similar
      to the situation in vivo. The reported method has significant advantages over
      established test procedures since it enables the researcher to assess the
      antimicrobial capacity of wound dressings to continue working under conditions
      that match those encountered in wounds. These key conditions are those that would
      be expected to impede the action of the dressing and protect the infecting
      organisms.

PMID- 17199768
TI  - Inflammatory inert poly(ethylene glycol)--protein wound dressing improves healing
      responses in partial- and full-thickness wounds.
AB  - In this study, a novel soft hydrogel system based on the poly(ethylene glycol)
      protein conjugates was evaluated as an occlusive wound dressing material. The
      hydrogel material, referred by the name of BioAquacare, contains up to 96% of the
      liquid and is formulated with phosphate-buffered saline and safe preservative to
      control bacterial load in the open wounds. Performance of the BioAquacare as a
      wound dressing material was assessed in partial- and full-thickness wounds in
      pigs. Wound analysis comprised macroscopic determination of the wound size,
      histological examination of the healing tissues and biochemical characterisation
      of wound exudates. The wounds treated with BioAquacare healed without any signs
      of inflammation, skin irritation, oedema or erythema. Cellular composition of the
      reepithelialised wounds was very similar to that of the normal skin, with a well
      developed stratum corneum and epithelial layer. It was observed that BioAquacare
      plays the role of a liquid compartment, which provides pronounced hydration
      effect and helps maintain a natural moist environment of the healing tissues.
      BioAquacare showed relatively low protein-absorbing activity, absorbing
      predominantly low-molecular-weight molecules, including interleukin (IL)-1beta,
      IL-6, transforming growth factor-beta1 and products of haemoglobin degradation.
      It is concluded that application of the moist BioAquacare dressing promotes fast
      reepithelialisation by creating favourable environment for keratinocytes
      proliferation and it also reduces scarring. The results show that BioAquacare can
      be considered as a safe, biocompatible and inflammatory inert wound dressing
      material.

PMID- 17199769
TI  - Estimating the risk of pressure ulcer development: is it truly evidence based?
AB  - The aim of the current method of screening patients is to identify risk factors
      that are considered to cause, or contribute to, pressure ulcer (PU) development.
      Yet screening has not resulted in a reduction in pressure ulcer development. The
      literature was reviewed to identify the level of evidence for the inclusion of
      risk factors in six published pressure ulcer risk-screening tools. Evidence for
      each risk factor was ranked according to the National Health and Medical Research
      Council levels of evidence with a modification. Three of 19 risk factors
      (mobility, continence and nutrition) included in more than one screening tool
      have been tested for association with pressure ulcer development. While varying
      degrees of immobility and decreased serum albumin are reported to significantly
      increase the risk for PU development, the direction of the relationship, i.e.
      causal or resultant of PU, is not always clear. No publications reported a
      significant causal link between incontinence and PU development. Inclusion of
      risk factors for PU in screening tools must be evidence based. Until other risk
      factors have been tested for positive predictive value, the Ramstadius approach
      to screening is the only evidence-based tool.

PMID- 17199770
TI  - Prognosis of stage I pressure ulcers and related factors.
AB  - The prognosis of stage I pressure ulcers cannot be predicted; therefore, nursing
      interventions for preventing their deterioration have not been clearly
      established. This study describes the clinical course of stage I pressure ulcers
      and prospectively investigates the factors related to their deterioration. Thirty
      one stage I pressure ulcers in 30 patients in a long-term care facility were
      studied, and morphological changes were assessed every day until the ulcers
      healed or deteriorated. The physiological changes were assessed by
      ultrasonography and thermography. Twenty ulcers healed, and 11 deteriorated. The
      characteristics of deterioration were as follows: (1) double erythema; (2) non
      blanchable erythema across the whole area determined by glass plate compression;
      (3) erythema away from the tip of the bony prominence; and (4) expanding erythema
      on the following day. We analysed the sensitivity, specificity, positive
      predictive value, negative predictive value and positive likelihood ratio for the
      diagnostic utility of the indicators of deterioration double erythema and
      distance from the tip of bony prominence, which can be instantly assessed without
      the use of any special device. The values were 36.4%, 95.0%, 80.0%, 73.1% and
      7.28, respectively. These results suggest that clinicians can predict the
      prognosis of stage I pressure ulcers by initial assessment and provide
      appropriate care based on the assessment.

PMID- 17199771
TI  - The potential of microscopic sterile sponge particles to induce foreign body
      reaction.
AB  - The sterile sponges may lose a significant amount of lint during their routine
      use in surgery, which is usually neglected. We designed an experimental model to
      evaluate the potential of sterile sponges to lose lint and to induce foreign body
      reaction in surgically created wounds. In 15 Wistar rats, separate subcutaneous
      pockets were created. Left-sided pockets were temporarily packed with sterile
      sponges, while the right-sided pockets remained empty. All the pockets were then
      irrigated with sterile saline. The presence of microscopic sponge particles was
      evaluated in the irrigation materials. After 4 weeks, the presence of
      inflammation and foreign body reaction were evaluated histologically. Microscopic
      sponge remnants were present in 14 of 15 samples collected from the left sides.
      The presence of foreign body giant cells with ingested sponge particles and
      formation of well-defined foreign body granulomas were observed only in samples
      collected from the left sides. A statistically significant difference was
      observed between the two sides when the intensity of inflammation was graded (P=
      0.012). Cotton sponges used in surgery are shown to have a potential of losing
      invisible microscopic particles that have a potential to induce foreign body
      reaction.

PMID- 17199773
TI  - Best practices in quantitative methods for developmentalists.

PMID- 17199783
TI  - Evaluation of renal tubular function in children taking anti-epileptic treatment.
AB  - AIM: To assess the effects of anti-epileptic drugs on renal tubular function.
      METHODS: Urinary N-acetyl-beta-D-glucosaminidase activity was measured in 114
      epileptic children (mean age 5.6 +/- 1.1 years) who were undergoing monotherapy
      with valproate (n = 46), carbamazepine (n = 34), lamotrigine (n = 13) and
      combined therapy with valproate+carbamazepine (n = 21). RESULTS: The urinary N
      acetyl-beta-D-glucosaminidase index of valproate (P < 0.01), carbamazepine (P <
      0.05) and polytherapy group (P < 0.01) were significantly elevated when compared
      with that of the control group. No significant difference in N-acetyl-beta-D
      glucosaminidase levels was found between the lamotrigine group and the control
      subjects. We found that the distribution of the N-acetyl-beta-D-glucosaminidase
      values of patients depended significantly on the length of therapy (P < 0.01).
      The level of urinary excretion of N-acetyl-beta-D-glucosaminidase was
      significantly higher in the patients who were taking long-term treatment (>10
      years) with valproate, carbamazepine and combined therapy than those taking
      therapy shorter than 10 years (P < 0.01). The mean serum concentrations of
      valproate and carbamazepine were 68.7 +/- 17.44 microg/mL and 5.41 +/- 1.23
      microg/mL, respectively. There was a significant correlation between the serum
      concentration of valproate and urinary N-acetyl-beta-D-glucosaminidase levels (r
      = 0.44, P < 0.01). There was also a significant correlation between the serum
      concentration of carbamazepine and N-acetyl-beta-D-glucosaminidase excretion (r =
      0.52, P < 0.01). CONCLUSION: The present study demonstrated that in patients
      treated with valproate and carbamazepine, an impairment of tubular function can
      be present, whereas lamotrigine does not cause any significant change.

PMID- 17199784
TI  - Atherosclerosis in haemodialysis patients without significant comorbidities:
      determinants of progression.
AB  - AIM: The aim of this prospective study was to assess the determinants of the
      progression of carotid artery intima-media thickness (CA-IMT) for 1 year in
      haemodialysis (HD) patients without significant comorbidities. METHODS: Fifty
      four HD patients younger than 55 years, without diabetes, obesity and any
      clinical evidence of cardiovascular disease (29 men, 25 women; mean age 33.3 +/-
      10 years; mean time on HD 49.4 +/- 43 months) were included in the 1-year study.
      CA-IMT was assessed at baseline and after 12 months. The difference in IMT
      between these two points of time was calculated (DeltaCA-IMT). C-reactive protein
      (CRP), erythrocyte sedimentation rate (ESR), haematocrit-corrected ESR, beta-2
      microglobulin, cardiac troponin I, lipid profile, fibrinogen, homocysteine, CaXP
      product, intact parathyroid hormone, haematocrit, albumin, uric acid levels,
      anthropometric parameters (age, body mass index), smoking, hypertension and left
      ventricular hypertrophy were recorded at baseline. RESULTS: The mean value for CA
      IMT at baseline (0.59 +/- 0.05 mm) was significantly lower than that at 12 months
      (0.64 +/- 0.07 mm) (P < 0.001). CA-IMT had increased in 41 patients (75.9%). Age
      (P = 0.02), CRP (P = 0.03), beta-2 microglobulin (P = 0.001) and left ventricular
      hypertrophy (P = 0.01) were independently related with CA-IMT at baseline. Age (P
      = 0.003) and CRP (P = 0.04) were the independent variables related with CA-IMT,
      measured at 12 months. DeltaCA-IMT correlated positively with age (r = 0.31, P <
      0.05). Age and sex were independent predictors of DeltaCA-IMT (R(2) for the model
      0.56). CONCLUSION: In addition to age and male sex, non-specific inflammation may
      have a possible role in the progression of atherosclerosis in HD patients without
      significant comorbidities.

PMID- 17199785
TI  - Heart valve calcifications in patients with end-stage renal disease: analysis for
      risk factors.
AB  - BACKGROUND: The prevalence of valve calcification (VC) in end-stage renal disease
      patients is high and information regarding risk factors is scarce. Our aims were
      to determine the prevalence of VC in our maintenance haemodialysis (HD)
      population and to examine some possible aetiologic factors for its occurrence.
      METHODS: We studied 90 patients (47 women) on maintenance HD for more than 12
      months. An M-mode two-dimensional echocardiogram was carried out to evaluate
      mitral, aortic VC and ventricular geometry. We calculated mean daily calcium
      intake for the phosphate intestinal chelaing in the previous year to
      echocardiogram date and also mean values from previous year of Ca, PO4, Ca x PO4,
      parathyroid hormone, lipide profile, nutritional and inflammatory marquers.
      Finally consumption of calcium and alfacalcidol was also noted. RESULTS: Thirty
      six patients (40%) presented with VC. Patients with VC were older and showed
      higher levels of serum calcium (92.00 +/- 7.54 vs 89.27 +/- 6.86 mg/L, P = 0.04),
      phosphorus (69.70 +/- 18.33 vs 44.90 +/- 12.43 mg/L, P < 0.0001), Ca x P product
      (6164.97 +/- 1797.64 vs 4024.70 +/- 1066.40 mg(2)/L(2), P < 0.0001) and poor
      ventricular geometry, as compared with patients without VC. Moreover, they
      required higher doses of alfacalcidol for treating secondary hyperparathyroidism
      (0.43 +/- 0.60 vs 0.11 +/- 0.46 microg/day, P < 0.0001). CONCLUSION: Findings of
      the present study are consistent with a role of altered calcium and phosphate
      metabolism in the pathogenesis of VC in HD patients.

PMID- 17199786
TI  - Influence of angiotensin converting enzyme inhibitor treatment on cardiac
      autonomic modulation in patients receiving haemodialysis.
AB  - BACKGROUND: Cardiovascular disease mortality among patients with end stage renal
      disease (ESRD) exceeds that which is predicted by traditional risk factors.
      Sudden death accounts for up to 15-38% of patients with ESRD found dead at home.
      Heart rate variability (HRV) is a reliable measure of autonomic modulation and
      has a very strong predictive value for ventricular arrhythmias and sudden death.
      A lower HRV is associated with increased risk. Modifying autonomic tone
      pharmacologically reduces death from dysrhythmia in the general population but
      has not been studied in ESRD. METHODS: We examined the effect of ramipril, an
      angiotensin converting enzyme inhibitor (ACEI) known in the general population to
      increase HRV, on cardiac function and heart rate variability in patients with
      renal failure. Eligible subjects on haemodialysis underwent a 2-week washout
      period free of ACEI or beta blockers, during which time hypertension was treated
      with amlodipine, which has been shown not to affect HRV. Haemodynamic and HRV
      measurements were obtained at baseline and after subjects were treated for 4
      weeks with an ACEI. RESULTS: Haemodynamics did not differ at 0 and 4 weeks.
      Baseline HRV values were markedly below those found in the general population,
      indicating pronounced predominance of sympathetic tone over vagal tone. Actual
      worsening of HRV with ACEI treatment was evident in several major time domains.
      The time domain SDNN (the standard deviation of all normal RR intervals) fell
      from 42.0 +/- 24.8 ms to 20.1 +/- 16.1 ms (P = 0.004) and the triangulation index
      fell from 178.0 +/- 94.0 to 115 +/- 59.2 (P = 0.01). A trend toward reduced HRV
      was seen in several other time domains. CONCLUSION: These findings suggest that,
      unlike the general population, treatment of ESRD patients with an angiotensin
      converting enzyme inhibitor may cause a deleterious shift toward increased
      cardiac sympathetic nervous system tone.

PMID- 17199787
TI  - Relationship between depressive affect and malnutrition-inflammation complex
      syndrome in haemodialysis patients.
AB  - BACKGROUND: Depression is associated with high mortality in haemodialysis (HD)
      patients, and can be associated with the poor oral intake that contributes to
      malnutrition. Malnutrition-inflammation complex syndrome (MICS) causes increased
      morbidity and mortality in HD patients. We investigated relationships between
      depressive affect, social support and various components of MICS in HD patients.
      METHODS: The subjects were 110 patients (65 men and 45 women, mean age 45.39 +/-
      14.73 years) on maintenance HD. The Beck Depression Inventory (BDI), Cognitive
      Depression Index (CDI), and the Multidimensional Scale of Perceived Social
      Support (MSPSS) were used to assess aspects of depressive affect in each subject.
      RESULTS: The mean dialysis duration was 53.04 +/- 38.15 months. The mean BDI and
      CDI scores were 12.10 +/- 7.43 and 8.40 +/- 5.72, respectively. Patients were
      divided into two subgroups according to CDI score (depressive affect >10 (n = 71)
      and non-depressive affect <or=10 (n = 39)). CDI score was correlated with
      malnutrition-inflammation score (MIS) (r = 0.24; P < 0.05), haemoglobin level (r
      = -0.23; P < 0.05) and MSPSS score (r = -0.28; P < 0.01). The subgroup with
      depressive affect had higher MIS (P < 0.01) and lower social support (P = 0.001)
      than the non-depressive affect group. Logistic regression analysis identified
      high MIS and low MSPSS score as independent risk factor for depression.
      CONCLUSIONS: The results suggest that MIS and MSPSS are the strongest predictors
      of depressive affect in HD patients. Further research is needed to understand the
      causal relationship between depressive affect and MICS in HD patients.

PMID- 17199788
TI  - Serum oxidized low-density lipoprotein is inversely correlated to telomerase
      activity in peripheral blood mononuclear cells of haemodialysis patients.
AB  - BACKGROUND: Telomerase preserves telomeres' function and structure preventing
      cellular senescence. Its activity is reduced in peripheral blood mononuclear
      cells (PBMC) of haemodialysis (HD) patients. The purpose of this study is to
      investigate the potential correlation between increased oxidative
      stress/inflammation and telomerase activity in PBMC of HD patients. METHODS:
      Telomerase activity was measured by PCR-ELISA in PBMC isolated from a group of 42
      HD patients and 39 subjects with estimated glomerular filtration rate >or=80
      mL/min (control group). Serum oxidized low-density lipoprotein (ox-LDL), tumour
      necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) were also measured
      in both groups by ELISA. RESULTS: Ox-LDL was negatively correlated to percentage
      telomerase activity in PBMC (r = -0.506, P = 0.000 in the whole group of 81 HD
      and normal subjects and r = -0.559, P < 0.001 in HD patients). TNF was also
      inversely associated with percentage telomerase activity in the whole group
      studied (r = -0.492, P = 0.000) while IL-10 was not. In stepwise multiple linear
      regression, taking into consideration the most important characteristics of the
      HD patients and control group, the only significant predictors for percentage
      telomerase activity in PBMC were ox-LDL and TNF (beta = -0.421, t = -4.083, P =
      0.000 and beta = -0.381, t = -3.691, P = 0.000, respectively) while examining
      separately HD patients, the predictors for the same parameter were ox-LDL and HD
      duration (beta = -0.671, t = -4.709, P = 0.000 and beta = -0.349, t = -2.447, P =
      0.023, respectively). CONCLUSION: Ox-LDL serum level is inversely correlated to
      telomerase activity in PBMC of HD patients. Our study proposes a new consequence
      of increased oxidative stress in HD patients: the premature cellular senescence
      potentially related to atherosclerosis through LDL oxidation.

PMID- 17199789
TI  - Proximal tubule endocytic apparatus as the specific renal uptake mechanism for
      vitamin D-binding protein/25-(OH)D3 complex.
AB  - The renal proximal tubule exhibits a very extensive apical endocytic apparatus
      that is involved in the reabsorption of molecules filtered in the glomeruli.
      Several key receptors appear to be involved in this function, which serves not
      only to conserve protein but also to reabsorb different vitamins in complex with
      their binding proteins. Recent research has established megalin as probably the
      most important receptor in this endocytosis process. Cubilin is another receptor
      identified in the proximal tubule endocytic apparatus. Because cubilin lacks
      transmembrane or cytoplasmic domains required for endocytosis, this receptor
      associates with megalin to recycle and internalize its ligands. Recent studies
      have shown that vitamin D-binding protein (DBP)/25-(OH)D3 complex is one of the
      megalin/cubilin ligands. Megalin knockout mice develop vitamin D deficiency and
      bone disease owing to an inability of the proximal tubules to capture the DBP/25
      (OH)D3 complexes from the glomerular filtrate. In the same way, kidney-specific
      megalin knockout mice have severe plasma vitamin D deficiency, hypocalcaemia and
      serious bone disease, like the complete megalin knockout mice. Anti-cubilin
      antibodies inhibit cellular uptake of DBP/25-(OH)D3 by up to 70%. Anti-megalin
      antibodies produced a similar reduction in DBP/25-(OH)D3 endocytosis. When both
      antibodies were applied, impairment of DBP/25-(OH)D3 was only slightly more
      impaired (around 80%), suggesting that cubilin and megalin function through the
      same endocytic pathway. Specific forms of renal Fanconi syndrome are associated
      with endocytic pathway dysfunction with disruption of megalin-mediated uptake
      DBP/25-(OH)D3 complex, producing metabolic bone disease in affected individuals
      as a prominent clinical finding.

PMID- 17199790
TI  - Troglitazone inhibits synthesis of transforming growth factor-beta1 and reduces
      matrix production in human peritoneal mesothelial cells.
AB  - AIM: Peritoneal matrix accumulation is a characteristic of peritoneal fibrosis
      (PF). Continuous ambulatory peritoneal dialysis (CAPD) patients with up
      regulation of transforming growth factor-beta1 (TGF-beta1) in their drained
      effluent show an increased risk of PF. Inhibition of TGF-beta1 expression in
      human peritoneal mesothelial cells (HPMC) may provide a potential treatment for
      PF. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are
      increasingly used in patients with diabetes, but their effects on extracellular
      matrix (ECM) turnover are unknown. The aims of this study were to investigate the
      effects of the PPAR-gamma agonist troglitazone on TGF-beta1 expression and matrix
      production in HPMC. METHODS: Human peritoneal mesothelial cells were cultured
      from human omentum by an enzyme digestion method, grown in a medium containing 30
      mmol/L D-glucose. TGF-beta1 expression and matrix production and turnover were
      measured in HPMC in the presence and absence of 15 micromol/L troglitazone. The
      mRNA expressions of TGF-beta(1), Collagen I (Col I) and fibronectin (FN) were
      determined by semiquantification reverse-transcriptive polymerase chain reaction
      (RT-PCR). The protein of TGF-beta1 was determined by ELISA and proteins of Col I,
      FN were determined by western blot. RESULTS: The mRNA expression and protein of
      TGF-beta(1), Col I, FN were significantly increased in HPMC stimulated with 30
      mmol/L D-glucose compared to the control group with F12 media (P < 0.01), which
      was reversed in the presence of troglitazone (15 micromol/L). Obvious decrease of
      TGF-beta(1) was found in troglitazone-treated groups as compared to groups
      stimulated with GS (P < 0.05). Exposure of HPMC to troglitazone reduced collagen
      I secretion (P < 0.05), and fibronectin secretion (P < 0.05). CONCLUSION:
      Troglitazone reduce the expression of TGF-beta(1) in HPMC stimulated by 30 mmol/L
      D-glucose, and reduces ECM production. These studies suggest that the PPAR-gamma
      agonists may have a specific role in ameliorating the course of progressive
      peritoneal fibrosis under long-term peritoneal dialysis states.

PMID- 17199791
TI  - Roxithromycin inhibits transforming growth factor-beta production by cultured
      human mesangial cells.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) plays an important role in
      progression of renal injury. However, few materials which inhibit TGF-beta have
      been known. Roxithromycin (ROX), macrolide antibiotics, is known to have anti
      inflammatory, immunomodulatory and tissue reparative effects besides its
      bacteriostatic activity, although the exact mechanism of its anti-inflammatory
      and immunomodulatory effects was not defined. We examined the effect of ROX on
      production of TGF-beta and type IV collagen by cultured human mesangial cells
      (HMC). METHODS: Human mesangial cells were incubated with several concentrations
      of ROX and TGF-beta and type IV collagen levels in the culture supernatants were
      measured by enzyme-linked immunoassay. Amount of TGF-beta mRNA was also
      quantified by using a colourimetric mRNA quantification kit and semiquantitative
      reverse transcriptase polymerase chain reaction. We also examined the effect of
      ROX on tyrosine kinase, MAP kinase and NF-kappaB stimulated by thrombin. RESULTS:
      Roxithromycin (0.1-10.0 microg/mL) inhibited TGF-beta production by HMC in a dose
      and time-dependent manner without inducing cell injury. ROX (10.0 microg/mL)
      also inhibited mRNA expression of TGF-beta in HMC. Thrombin (5 U/mL) stimulated
      TGF-beta production by HMC and ROX significantly inhibited the stimulating effect
      of thrombin on TGF-beta production. ROX also inhibited the increment of type IV
      collagen production stimulated by thrombin. ROX (10.0 microg/mL) suppressed the
      thrombin-induced NF-kappaB activation, although ROX did not inhibit the
      activation of tyrosine kinase and MAP kinase by thrombin. CONCLUSION:
      Roxithromycin has an inhibitory effect on TGF-beta production by HMC possibly via
      inhibition of NF-kappaB. ROX may be a potential agent for the treatment of
      glomerulosclerosis.

PMID- 17199792
TI  - A long story: from suspicion to identification of non-diabetic renal diseases in
      patients with diabetic mellitus.

PMID- 17199793
TI  - Non diabetic renal disease in type 2 diabetes mellitus.
AB  - AIM: The aim of this analysis of renal biopsies in people with type 2 diabetes
      was to know the prevalence and nature of non-diabetic renal disease (NDRD) and to
      note its correlation with the duration of diabetes, extent of proteinuria and
      presence or absence of retinopathy. METHODS: From January 2000 to December 2004,
      160 people with type 2 diabetes with clinically suspected NDRD underwent renal
      biopsy reported by a single pathologist. The case records of these patients were
      retrospectively analysed. Based on the biopsy findings, patients were grouped as
      Group I, isolated NDRD; Group II, NDRD with underlying diabetic
      glomerulosclerosis; and Group III, isolated diabetic glomerulosclerosis. The
      relation of histology with clinical profile in each group was noted and
      statistically analysed using strata 6 software. RESULTS: Of the 160 patients
      studied, 118 were males and 42 were females (2.8:1). The average age was 51.35
      years (30-79). Indications for renal biopsy included: nephrotic syndrome in 55
      (34.37%), acute renal failure (ARF) in 49 (30.62%), rapidly progressive renal
      failure (RPRF) in 24 (15%), absent retinopathy in 19 (11.87%), haematuria in 10
      (6.25%) and acute on chronic renal failure (CRF) in three (1.87%) patients. Group
      I included 68 patients (42.50%), Group II included 48 patients (30%) and Group
      III included 44 patients (27.50%). The mean duration of diabetes was 5.37, 10.12
      and 6.86 years in Groups I, II and III respectively. The duration of diabetes was
      significantly less in Group I compared with Group II and III combined (5.37 vs
      8.53; P < 0.001). Diabetic retinopathy was absent in 61 (38.13%) patients, of
      whom 41 (67.21%) had isolated NDRD. The most common NDRD were acute interstitial
      nephritis (18.1%), post infectious glomerulonephritis (17.24%), membranous
      nephropathy (11.20%) and focal segmental glomerulosclerosis (7.75%). CONCLUSIONS:
      Prevalence of NDRD (either isolated or superimposed on underlying diabetic
      glomerulosclerosis) is very high in appropriate clinical settings. The shorter
      duration of diabetes and the absence of retinopathy, especially when associated
      with nephrotic proteinuria, strongly predict NDRD.

PMID- 17199794
TI  - Angiotensin converting enzyme gene polymorphisms do not predict the course of
      idiopathic nephrotic syndrome in Swiss children.
AB  - AIM: Contradictory reports exist about a correlation of angiotensin I converting
      enzyme (ACE) gene polymorphisms to the outcome of idiopathic nephrotic syndrome
      (INS) in children. We investigated the frequency of ACE polymorphisms and their
      impact on the clinical course of INS in children in a Swiss hospital. METHODS:
      The ACE gene polymorphism (I, insertion; D, deletion) was assessed in 32 children
      - 22 with steroid-sensitive INS and 10 with steroid-resistant INS - with a median
      age at onset of INS of 2.9 years (range 1.1-15.0). Polymerase chain reaction
      amplification was performed on genomic DNA isolated from blood leucocytes.
      Results were correlated to clinical course and renal morphology. RESULTS: The ACE
      genotype was I/I, I/D and D/D in two, 12 and eight patients, respectively, with
      steroid-sensitive INS, and in one, eight and one patient, respectively, with
      steroid resistance. Renal morphology, available in 25 patients showed minimal
      change glomerulopathy in 17 patients (14 steroid-sensitive; three steroid
      resistant) and focal segmental glomerulosclerosis in eight (one steroid
      sensitive; seven steroid-resistant). There was no significant correlation between
      ACE genotype and steroid responsiveness, histology or outcome. ACE genotype was
      I/I, I/D and D/D in none, 12 and five patients, respectively, with minimal change
      glomerulopathy, and in one, five and two patients, respectively, with focal
      segmental glomerulosclerosis. Six patients with steroid-resistant nephrotic
      syndrome went into end stage renal disease; ACE genotype was I/I in one and I/D
      in five, but none were D/D. CONCLUSION: In contrast to previous reports, ACE gene
      polymorphism is irrelevant for clinical outcome, steroid responsiveness or
      morphology in Swiss children with INS.

PMID- 17199795
TI  - Renal anaemia: recent developments, innovative approaches and future directions
      for improved management.
AB  - The morbidity, mortality and economic burden of chronic kidney disease (CKD) and
      associated anaemia are substantial. With the increasing numbers of patients who
      are likely to be affected in the future, approaches are required to improve
      anaemia management without increasing the burden on health-care professionals. A
      multidisciplinary approach to treatment, where early initiation of erythropoiesis
      stimulating agents (ESA) is encouraged, may improve patient outcomes. Recent
      studies also suggest that the early use of iron therapy in patients with CKD not
      on dialysis may be associated with beneficial effects on haemoglobin levels.
      Another strategy to reduce the burden on health-care providers is to simplify
      anaemia management by extending the administration interval of ESA. Indeed,
      recent studies have explored the efficacy of extending the administration
      interval of ESA in clinical practice in CKD patients on dialysis and not on
      dialysis. The ability to maintain haemoglobin levels within guideline ranges at
      extended administration intervals may improve patient care and reduce the
      workload of health-care providers.

PMID- 17199796
TI  - Undiagnosed renal impairment in patients with and without diabetes with normal
      serum creatinine undergoing percutaneous coronary intervention.
AB  - HYPOTHESIS: The recent Dialysis Outcome Quality Initiative publication on the
      evaluation, classification and stratification of chronic kidney disease (CKD)
      states that individuals with a reduced glomerular filtration rate (GFR) is at
      greater risk for cardiovascular diseases and cardiac deaths. AIM: To determine
      the prevalence of kidney dysfunction in a cohort of 1390 patients with and
      without diabetes with normal serum creatinine undergoing percutaneous coronary
      intervention. METHODS: Kidney function was estimated using simplified MDRD,
      Cockcroft-Gault and Jeliffe formulas. RESULTS: Normal serum creatinine was
      observed in 93% patients. Mean estimated GFR in 1068 non-diabetic patients was
      significantly higher than in 322 diabetic patients (all formulas). Diabetic
      females had significantly lower creatinine and estimated GFR, higher high-density
      lipoprotein and platelet count than diabetic males. A very high prevalence of CKD
      up to 77% was found in studied diabetic patients. Clinically significant CKD (as
      defined by GFR < 60 mL/min) was found in 13.0-33.8% patients depending on the
      formula used to estimate GFR. CONCLUSION: The prevalence of CKD (stages 2-3) is
      high in diabetic patients undergoing percutaneous coronary intervention despite
      normal creatinine. The risk of contrast nephropathy with worse outcomes is
      enhanced in these patients, particularly in elderly and females. Evaluation of
      renal function is important in order to select the appropriate strategy to reduce
      the cardiovascular risk.

PMID- 17199797
TI  - Effect of ergocalciferol supplementation on serum parathyroid hormone and serum
      25-hydroxyvitamin D in chronic kidney disease.
AB  - AIM: To assess the impact of the administration of ergocalciferol on serum
      parathyroid hormone levels at different stages of chronic kidney disease (CKD).
      METHODS: A continuous series of 85 patients with stages 3-5 CKD but excluding
      patients on dialysis referred to the Kaiser Kidney Program were followed.
      Baseline serum intact parathyroid hormone (iPTH) and serum 25(OH)D levels were
      measured. All patients were administered ergocalciferol in doses ranging from 800
      iu/day to 100,000 iu/week. We obtained serum levels of iPTH and 25(OH)D for a
      post-treatment endpoint after a median treatment period of 90 days. RESULTS: Pre-
      and post-treatment serum iPTH levels displayed a mean difference of 2.8 pmol/L
      (95% CI 1.3-4.4, P < 0.001). Patients with stage 4 CKD had a mean difference of
      3.6 pmol/L (95% CI 1.7-5.5, P < 0.001) between pre- and post-iPTH levels. Serum
      iPTH levels decreased among CKD stages 3 and 5, but were not statistically
      significant. All CKD groups analysed in the present study had significant
      increases in serum 25(OH)D levels. None of the study population required
      cessation of vitamin D therapy and no adverse outcomes were reported. CONCLUSION:
      Ergocalciferol supplementation appears a safe and effective treatment for CKD
      populations which may raise levels of serum 25(OH)D levels and decrease iPTH
      levels.

PMID- 17199799
TI  - Renal mass showing normal ultrasonographic findings.

PMID- 17199798
TI  - From marrow oedema to osteonecrosis: common paths in the development of post
      transplant bone pain.
AB  - Osteonecrosis, the calcineurin-inhibitor-induced pain syndrome and transient
      marrow oedema may occur after renal transplantation, are generally painful and
      can be diagnosed by X-ray, radionuclide scan or magnetic resonance imaging. They
      share features of increased intraosseous pressure, compromised vascular supply,
      marrow oedema and the development of a 'bone compartment syndrome'.
      Glucocorticoid dosage is the most commonly implicated risk factor for
      osteonecrosis. Mechanisms may include the differentiation of mesenchymal stem
      cells to adipocytes causing increased intraosseous pressure and collapse of
      marrow sinusoids, as well as increased osteoblast and osteocyte apoptosis. Some
      of these effects may be ameliorated by lipid lowering drugs. Calcineurin
      inhibitors, particularly cyclosporine, may increase the risk of osteonecrosis
      because of vasoconstrictive effects and sirolimus may influence the development
      of osteonecrosis by potentiating the effects of calcineurin inhibitors or by
      influencing the lipid profile. For osteonecrosis, early stages are generally
      managed conservatively or with core decompression sometimes accompanied by bone
      grafting and more recently the injection of bone morphogenic protein. The use of
      iloprost to improve blood flow and bisphosphonates and RANK-ligand inhibition to
      reduce osteoclastic resorption of remaining trabecular structures are as yet
      unproven strategies. Unfortunately, the rate of total hip arthroplasty remains
      high. For the calcineurin-inhibitor-induced pain syndrome and transient marrow
      oedema, calcium channel blockers, the reduction or withdrawal of calcineurin
      inhibitors and core decompression have been used. Although a lack of randomized
      controlled trials makes management decisions difficult, early recognition of
      these bone pain syndromes affords the best opportunity for avoiding prolonged
      pain or joint replacement surgery.

PMID- 17199800
TI  - Carnitine'S protective effect on oxidative stress is mediated by heme oxygenase
      1.

PMID- 17199802
TI  - Mercury (micro)biogeochemistry in polar environments.
AB  - The contamination of polar regions with mercury that is transported as inorganic
      mercury from lower latitudes has resulted in the accumulation of methylmercury in
      the food chain of polar environments, risking the health of humans and wildlife.
      This problem is likely to be particularly severe in coastal marine environments
      where active cycling occurs. Little is currently known about how mercury is
      methylated in polar environments. Relating observations on mercury deposition and
      transport through polar regions to knowledge of the microbiology of cold
      environments and considering the principles of mercury transformations as have
      been elucidated in temperate aquatic environments, we propose that in polar
      regions (1) variable pathways for mercury methylation may exist, (2) mercury
      bioavailability to microbial transformations may be enhanced, and (3) microbial
      niches within sea ice are sites where active microorganisms are localized in
      proximity to high concentrations of mercury. Thus, microbial transformations, and
      consequently mercury biogeochemistry, in the Arctic and Antarctic are both unique
      and common to these processes in lower latitudes, and understanding their
      dynamics is needed for the management of mercury-contaminated polar environments.

PMID- 17199805
TI  - A sympathetic but critical assessment of nanotechnology initiatives.

PMID- 17199806
TI  - The politicization of science and technology: its implications for
      nanotechnology.
AB  - The development of nanotechnology intensifies challenges to the traditional
      understanding of how to pursue scientific and technological knowledge. Science
      can no longer be construed simply as the ideal of the quest for truth (i.e.,
      "pure science"). Science has become the source of economic power and political
      power. In this paper, I argue that nanotechnology is a cardinal exemplar of "this
      politicization." At the same time, I assert that this new scientific ethos offers
      the possibility of a better integration of ethical and philosophical reflections
      at the core of scientific and technological development.

PMID- 17199803
TI  - DNA and its cationic lipid complexes induce CpG motif-dependent activation of
      murine dendritic cells.
AB  - Unmethylated CpG motifs in bacterial DNA, but not in vertebrate DNA, are known to
      trigger an inflammatory response of antigen-presenting cells (APC). In this
      study, we investigated the cytokine release from murine dendritic cells (DC) by
      the addition of various types of DNA in the free or complexed form with cationic
      lipids. Naked plasmid DNA and Escherichia coli DNA with immunostimulatory
      unmethylated CpG motifs induced pro-inflammatory cytokine secretion from
      granulocyte-macrophage colony-stimulating factor (GM-CSF)-cultured bone marrow
      derived DC and the DC cell-line, DC2.4 cells, though vertebrate calf thymus DNA
      (CT DNA) with less CpG motifs did not. These characteristics differed from mouse
      peritoneal resident macrophages that do not respond to any naked DNA. The amount
      of cytokines released from the DC was significantly increased by complex
      formation with cationic lipids when CpG-motif positive DNAs were used. Unlike
      murine macrophages or Flt-3 L cultured DC, GM-CSF DC did not release inflammatory
      cytokines in response to the addition of CT DNA/cationic lipid complex,
      suggesting that the activation is completely dependent on CpG motifs. Taken
      together, the results of the present study demonstrate that murine DC produce pro
      inflammatory cytokines upon stimulation with CpG-containing DNAs and the
      responses are enhanced by cationic lipids. These results also suggest that DC are
      the major cells that respond to naked CpG DNA in vivo, although both DC and
      macrophages will release inflammatory cytokines after the administration of a
      DNA/cationic lipid complex.

PMID- 17199807
TI  - Drawing the boundaries of nanoscience--rationalizing the concerns?
AB  - Nanotechnology as an emerging field is strongly related to visionary prospects
      which are disposed to reappear as dystopian concerns. As long as nanotechnology
      does not provide reliable criteria for assessing these worries as rational or as
      irrational they remain a challenge for ethical reflection. Given this
      underdetermination, many nanovisions and their corresponding concerns should
      therefore be considered as "arational." For that reason, a "constructivist"
      stance is endorsed which does not seek to take part in discussions as to how
      ethicists should cope with controversial worries, but tries to observe how
      concerns are managed by different social actors. This perspective allows us to
      remodel some concerns such as "grey goo" not solely as a societal reaction, but
      also as challenging and irritating factors. As such they potentially initiate two
      different processes simultaneously: a differentiation in terms of demarcating
      science from non-science on the one hand, and a rationalization of concerns on
      the other. Analyzing these processes empirically allows to reconstruct how
      "arational" concerns are socially made rational or, on the contrary, irrational.

PMID- 17199808
TI  - The national nanotechnology initiative and the social good.
AB  - The purpose of the National Nanotechnology Initiative (NNI) is to promote
      nanotechnology in a way that benefits the citizens of the United States. It
      involves a commitment to support responsible development of nanotechnology. The
      NNI's enactment of this commitment is critically assessed. It is concluded that
      there are not adequate avenues within the NNI by which social and ethical issues
      can be raised, considered, and, when appropriate, addressed.

PMID- 17199809
TI  - Lessons from the sustainability movement: toward an integrative decision-making
      framework for nanotechnology.
AB  - The author argues that bioethicists must develop alternative approaches to
      facilitate the study of the conditions for the responsible development of
      nanotechnologies. Proponents of "sustainability" have developed a useful model to
      integrate multiple perspectives into the evaluation of the impact of technologies
      on global ecological integrity under conditions of uncertainty.

PMID- 17199810
TI  - Cognitive barriers in perception of nanotechnology.
AB  - This article is concerned with predictions of future events, such as
      technological achievements and changes in the human condition that they will
      bring about. Cognitive barriers arise when human agents are either asked or
      forced to make judgments and decisions with respect to unknown singular events.
      This article argues that barriers such as an aversion to not knowing and the
      impossibility to believe trump expert and ordinary human reasoning. These
      barriers apply to nanotechnology. To avoid undesired societal effects arising
      from them, this essay proposes a set of steps designed to foster responsible
      public dialogue.

PMID- 17199811
TI  - Using trading zones and life cycle analysis to understand nanotechnology
      regulation.
AB  - This article reviews the public health and environmental regulations applicable
      to nanotechnology using a life cycle model from basic research through end-of
      life for products. Given nanotechnology's immense promise and public investment,
      regulations are important, balancing risk with the public good. Trading zones and
      earth systems engineering management assist in explaining potential solutions to
      gaps in an otherwise complex, overlapping regulatory system.

PMID- 17199812
TI  - Nanotechnology: the challenge of regulating known unknowns.
AB  - Media reports of the health hazards posed by nano-sized particles (NSPs) have
      turned a white hot spotlight on the risks of nanotechnology. Worried about the
      risks posed to workers producing nano-materials, the Washington Post has labeled
      nanotechnology a "seat-of-the-pants occupational health experiment." This article
      examines our emerging knowledge base about the hazards of two types of exposure:
      inhalation of NSPs and topical application of products containing NSPs. It argues
      that a clear-eyed evaluation of the benefits and risks of nanotechnology is made
      extremely difficult by the marriage of a complex science with a venture
      capitalist-like hype. It then suggests that, absent additional statutory
      authority, governmental regulators cannot readily address the risks posed by
      these products. This regulatory inaction leaves a significant role for the
      private insurance market, a role that regulators should support in tangible ways
      outlined in the article.

PMID- 17199813
TI  - Transnational models for regulation of nanotechnology.
AB  - Like all technologies, nanotechnology will inevitably present risks, whether they
      result from unintentional effects of otherwise beneficial applications, or from
      the malevolent misuse of technology. Increasingly, risks from new and emerging
      technologies are being regulated at the international level, although governments
      and private experts are only beginning to consider the appropriate international
      responses to nanotechnology. In this paper, we explore both the potential risks
      posed by nanotechnology and potential regulatory frameworks that law may impose.
      In so doing, we also explore the various rationales for international regulation
      including the potential for cross-boundary harms, sharing of regulatory expertise
      and resources, controlling protectionism and trade conflicts, avoiding a "race to
      the bottom" in which governments seek economic advantage through lax regulation,
      and limiting the "nano divide" between North and South. Finally, we examine some
      models for international regulation and offer tentative thoughts on the prospects
      for each.

PMID- 17199814
TI  - Converging NBIC technologies for improving human performance: a critical
      assessment of the novelty and the prospects of the project.
AB  - This contribution focuses on two claims advanced by the proponents of the project
      of "Converging Technologies for Improving Human Performance." Firstly, it is
      maintained that this project represents something genuinely new and quite unique.
      Secondly, it is argued that the future prospects of the project are
      extraordinarily positive. In order to critically assess both claims this paper
      first focuses on the question of whether there is actually anything genuinely new
      about the project of improving human performance by means of converging NBIC
      technologies. In addition it is analyzed whether the project warrants that we be
      optimistic about its future prospects.

PMID- 17199815
TI  - The social conditions for nanomedicine: disruption, systems, and lock-in.
AB  - Here we consider two ways that nanomedicine might be disruptive. First, low-end
      disruptions that are intrinsically unpredictable but limited in scope, and
      second, high end disruptions that involve broader societal issues but can be
      anticipated, allowing opportunity for ethical reflection.

PMID- 17199816
TI  - Offense-defense aspects of nanotechnologies: a forecast of potential military
      applications.
AB  - Potential military applications of nanotechnology will evolve in the next few
      decades. The implications for both defense and offense should be carefully
      assessed. Nanotechnology can push major changes in stability, and shape the
      consequences of future conflict.

PMID- 17199817
TI  - Is the tobacco settlement constitutional?
AB  - In August 2005, the Competitive Enterprise Institute (CEI), a conservative
      advocacy organization, filed a lawsuit in Louisiana challenging the legality of
      the 1998 Master Settlement Agreement (MSA). The suit alleges that the MSA, under
      which the states receive monetary payments and the four major tobacco companies
      are insulated from price competition, violates the Compact Clause and other
      provisions of the U.S. Constitution. This lawsuit threatens to unravel of one of
      the most significant opportunities to improve public health in United States
      history. We consider the merits of the lawsuit, the problems with the MSA that it
      highlights, and the potential consequences of the suit for public health.

PMID- 17199818
TI  - Heterozygote carrier testing in high schools abroad: what are the lessons for the
      U.S.?
AB  - The main value of carrier detection in the general population is to determine
      reproductive risks. In this manuscript I examine the practice of providing
      carrier screening programs in the school setting. While the data show that high
      school screening programs can achieve high uptake, I argue that this may reflect
      a lack of full understanding about risks, benefits, and alternatives, and the
      right not to know. It may also reflect the inherent coercion in group testing,
      particularly for adolescents who are prone to peer pressure. The problem of
      carrier screening in the schools is compounded when the condition has a
      predilection for certain groups based on race, ethnicity or religion. I examine
      programs around the world that seek to test high school students for Tay Sachs
      and Cystic Fibrosis carrier status. I argue that carrier programs should be
      designed so as to minimize stigma and to allow individuals to refuse. The
      mandatory school environment cannot achieve this. Rather, I conclude that
      screening programs should be designed to attract young adults and not adolescents
      to participate in a more voluntary venue.

PMID- 17199819
TI  - Regulation of firearm dealers in the United States: an analysis of state law and
      opportunities for improvement.
AB  - Firearms were associated with 30, 136 deaths in the United States in 2003. Most
      guns are initially sold to the public through a network of retail dealers.
      Licensed firearm dealers are an important source of guns for criminals and gun
      traffickers. Just one percent of licensed dealers were responsible for more than
      half of all guns traced to crime. Federal law makes it difficult for ATF to
      inspect and revoke the licenses of problem gun dealers. State licensing systems,
      however, are a greatly under-explored opportunity for firearm dealer oversight.
      We identify and categorize these state systems to identify opportunities for
      interventions to prevent problem dealers from supplying guns to criminals,
      juveniles, or gun traffickers. Just seventeen states license gun dealers. Twenty
      three states permit routine inspections of dealers but only two mandate that
      those inspections occur on a regular basis. Twenty-six states impose record
      keeping requirements for gun sales. Only thirteen states require some form of
      store security measures to minimize firearm theft. We conclude with
      recommendations for a comprehensive system of state licensing and oversight of
      gun dealers. Our findings can be useful for the coalition of more than fifty U.S.
      mayors that recently announced it would work together to combat illegal gun
      trafficking.

PMID- 17199820
TI  - Supernumerary pregnancy, collective harm, and two forms of the nonidentity
      problem.
AB  - An interesting question, in both the moral and the legal context, is whether
      babies born of an infertility treatment-induced supernumerary pregnancy (or
      ITISP) are properly considered to have been harmed. One might wonder how such a
      question could even arise in the face of data that clearly demonstrate that ITISP
      leaves an unduly large number of babies blind, deaf, and palsied, and facing
      lifelong disabilities. In fact, however, a number of arguments, based on the
      problem of collective form and two forms of the so-called "nonidentity problem,"
      challenge the claim of harm in the ITISP context. The purpose of the present
      paper is to establish, as against these arguments, that harm has been imposed on
      the ITISP-damaged offspring.

PMID- 17199821
TI  - The balm of Gilead: is the provision of treatment to those who seroconvert in HIV
      prevention trials a matter of moral obligation or moral negotiation?
AB  - Must treatment be provided to subjects who acquire HIV during the course of a
      prevention study? An analysis of ethical foundation, regulation, and recent
      argumentation provides no basis for the obligation. We outline an alternative
      approach to the problem based on moral negotiation.

PMID- 17199822
TI  - Meeting the growing demands of genetic research.

PMID- 17199823
TI  - To tell or not to tell: disclosing medical error.

PMID- 17199824
TI  - The United States Supreme Court and health law: the year in review.

PMID- 17199826
TI  - Recent developments in health law. Constitutional law: despite reservations, the
      second circuit defers to state court's determination that a preponderance of the
      evidence standard is constitutional for recommitment of NRRMDD defendants--Ernst
      J. v. Stonea.

PMID- 17199827
TI  - Recent developments in health law. ERISA: subrogation, Sereboff, and the "make
      whole" doctrine: the D.C. circuit defines ambiguity in ERISA subrogation clauses-
      Moore v. Capital Care, Inc.

PMID- 17199828
TI  - Recent developments in health law. Civil rights: prisoners' right to treatment
      information under Pabon v. Wright.

PMID- 17199830
TI  - Guidelines for the best care of chronic wounds.

PMID- 17199831
TI  - Guidelines for the treatment of venous ulcers.

PMID- 17199832
TI  - Guidelines for the treatment of pressure ulcers.

PMID- 17199833
TI  - Guidelines for the treatment of diabetic ulcers.

PMID- 17199834
TI  - Guidelines for the treatment of arterial insufficiency ulcers.

PMID- 17199838
TI  - Effect of chronic diseases and associated psychological distress on health
      related quality of life.
AB  - BACKGROUND: The purpose of this study was to clarify the correlations between the
      presence of comorbidities and psychological distress and health-related quality
      of life (HRQL). This was a population-based cross-sectional study. METHODS:
      Parents and grandparents of students from seven randomly selected primary schools
      in the city centre were asked to answer questionnaires sent by their children.
      All subjects were questioned for somatic diseases, psychological distress and
      HRQL by Health Questionnaire, Hospital Anxiety and Depression scale and short
      form-12 health survey, respectively. RESULTS: Out of 5024 parents and
      grandparents (mean age 52.3 +/- 14.3 years, range 20-104 years) of primary school
      students 4605 returned the questionnaires, a figure that corresponds to the
      overall response rate of 91.6%. Chronic diseases substantially reduced HRQL and
      this effect did not differ markedly with the type of chronic disease. Association
      of comorbidities with psychological distress further impaired HRQL. As the number
      of chronic diseases was increased, HRQL and physical and mental functioning
      declined. The worst HRQL was observed in subjects who had five or more
      comorbidities associated with psychological distress. CONCLUSION: The present
      study indicates significant adverse effects of chronic diseases and psychological
      distress on HRQL in adults, the effect of psychological distress being the most
      important. Our results lead us to suggest that in the management of
      comorbidities, the detection of the presence and severity of associated
      psychological distress and its treatment, besides the specific treatment of
      comorbidities, may provide dramatic improvement in HRQL of the patients.

PMID- 17199837
TI  - Urban indigenous health.

PMID- 17199839
TI  - Assessment by human research ethics committees of potential conflicts of interest
      arising from pharmaceutical sponsorship of clinical research.
AB  - BACKGROUND: Conflicts of interest arising from pharmaceutical industry
      sponsorship of clinical research have the potential to bias research outcomes and
      ultimately prejudice patient care. It is unknown how Australian Human Research
      Ethics Committees (HREC) assess and manage such conflicts of interest. We aimed
      to gain an understanding of how HREC approach the problem of potential conflicts
      of interest arising from pharmaceutical sponsorship of clinical research. METHOD:
      We conducted a survey of HREC chairpersons in New South Wales. RESULTS: HREC vary
      widely in their approaches to conflicts of interest, including in their use of
      National Health and Medical Research Council guidelines, which were often
      misinterpreted or overlooked. Many committees rely primarily on researchers
      disclosing potential conflicts of interest, whereas a majority of HREC use
      disclosure to research participants as the primary tool for preventing and
      managing conflicts of interest. Almost no HREC place limitations on researcher
      relationships with pharmaceutical companies. CONCLUSION: These findings suggest
      reluctance on the part of HREC to regulate many potential conflicts of interest
      between researchers and pharmaceutical sponsors, which may arise from uncertainty
      regarding the meaning or significance of conflicts of interest in research, from
      ambiguity surrounding the role of HREC in assessing and managing conflicts of
      interest in research or from misinterpretation or ignorance of current National
      Health and Medical Research Council guidelines. Further review of policies and
      practices in this important area may prove beneficial in safeguarding clinical
      research and patient care while promoting continuing constructive engagement with
      the pharmaceutical industry.

PMID- 17199840
TI  - Analysis of multidisciplinary lung cancer practice.
AB  - BACKGROUND: The aim of this study was to describe the activity of a lung cancer
      multidisciplinary clinic (MDC) and examine whether this model of clinical
      practice results in adherence to best-practice guidelines. METHODS: Prospective
      analysis of demographic and clinical data in 431 patients referred to a lung
      cancer MDC for the management of known or suspected thoracic malignancy.
      Adherence was documented to clinically relevant guideline recommendations
      concerning timely and evidence-based lung cancer management. RESULTS: Of 431
      patients, 257 were diagnosed with primary lung cancer, mean age 68 years, 70% men
      and 90% current smokers or ex-smokers. Only 21% were referred with known
      malignancy and 28% were asymptomatic. Overall, 51% had stages I and II non-small
      cell lung cancer, with this bias towards early-stage disease greatest in patients
      from rural areas. Histological confirmation of lung cancer was obtained in 92%.
      There was a high rate of adherence to international guideline recommendations
      concerning timely lung cancer diagnosis, staging and treatment implementation.
      Similarly, there was adherence to selected key evidence based recommendations for
      lung cancer management contained in national guidelines. CONCLUSION: Within a
      MDC, patients receive timely diagnosis, staging and treatment according to
      evidence-based guideline recommendations. The high proportion of patients
      receiving active treatment has implications for resource allocation. There is a
      referral bias towards patients with early non-small-cell lung cancer,
      particularly in rural patients, suggesting that further education about advances
      in metastatic lung cancer management is required. This study would support the
      establishment of regional lung cancer services with links to fully resourced MDC.

PMID- 17199841
TI  - High-risk febrile neutropenia in Auckland 2003-2004: the influence of the
      microbiology laboratory on patient treatment and the use of pathogen-specific
      therapy.
AB  - BACKGROUND: International guidelines recommend routine microbiological assessment
      of patients with febrile neutropenia, but do not recommend a change from broad
      spectrum antibiotic therapy to pathogen-specific therapy when a clinically
      relevant organism has been isolated. The aim of the study was to determine the
      aetiology of febrile neutropenia in adult haematology patients at Auckland City
      Hospital, to document the changes in treatment made following isolation of a
      clinically relevant organism and to assess adverse outcomes in any patient who
      received pathogen-specific therapy after a positive culture result. METHODS: The
      results of all microbiological tests together with antibiotic therapy were
      recorded from consecutive patients with fever and a neutrophil count <0.5 x
      10(9)/L over 1 year beginning in May 2003. RESULTS: One thousand one hundred and
      ninety-six specimens were collected from 81 patients during 116 episodes of
      febrile neutropenia. A pathogen was isolated from blood cultures in 40 episodes:
      Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for
      35%. Isolation of a pathogen from blood cultures resulted in a change of
      treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes,
      antibiotic therapy was optimized to a single pathogen-specific agent. No adverse
      events or subsequent changes in antibiotic therapy occurred in any of these 12
      patients. Isolation of a pathogen from specimens other than blood seldom led to a
      change in therapy. CONCLUSION: Isolation of a pathogen from blood cultures often
      allows antibiotic therapy to be simplified to a pathogen-specific regimen.
      Further study of this approach is warranted.

PMID- 17199842
TI  - Sudden cardiac death in the young: a clinical genetic approach.
AB  - The sudden death of a young person is a devastating event for both the family and
      community. Over the last decade, significant advances have been made in
      understanding both the clinical and genetic basis of sudden cardiac death in the
      young. Many of the causes of sudden death in the young are due to genetic heart
      disorders, which can lead to both structural (e.g. hypertrophic cardiomyopathy)
      and arrhythmogenic (e.g. familial long QT syndrome) abnormalities. Most commonly,
      sudden cardiac death in the young can be the first presentation of an underlying
      heart problem, leaving the family at a loss as to why an otherwise healthy young
      person has died. Not only is this a tragic event for those involved, but it also
      presents a medical challenge to the clinician involved in the management of the
      surviving family members. Evaluation of families requires a multidisciplinary
      approach, which should include cardiologists, a clinical geneticist, a genetic
      counsellor and the forensic pathologist directly involved in the sudden death
      case. This multifaceted cardiac genetic service is crucial in the evaluation and
      management of the clinical, genetic, psychological and social complexities
      observed in families in which there has been a young sudden cardiac death.

PMID- 17199843
TI  - Assessment and treatment of pulmonary arterial hypertension: an Australian
      perspective in 2006.
AB  - Pulmonary arterial hypertension is a group of diseases which forms a small subset
      of those with elevated pulmonary artery pressure (pulmonary hypertension). The
      recent development of selective pulmonary vasodilator has lead to a substantial
      resurgence of interest in what have been previously regarded as rare and
      incurable diseases. This review aims to describe the spectrum of pulmonary
      vascular diseases, the evolving understanding as to pathogenesis, the evolving
      evidence of efficacy for drug therapies, trying to put this into a contemporary
      Australian context. Several key pathogenic pathways may be involved:
      prostacycline, Nitric Oxide-cGMP-phosphodiesterase 5 and endothelin- all of which
      are exploited for therapeutic benefit by newly available drug therapies. A
      recently modified classification system reasserts the importance of precise
      diagnosis. The cardinal symptom of exertional dyspnea warrants careful evaluation
      in an attempt to prevent (frequently occurring) substantial delay in diagnosis.
      Echocardiogram is the cornerstone of screening for pulmonary arterial
      hypertension; however, a detailed evaluation including a carefully performed
      right heart catheterisation with sufficient data to allow calculation of
      pulmonary vascular resistance is key to accurate diagnosis. These new approaches
      to therapy are already substantially improving quality of life and prognosis.

PMID- 17199844
TI  - Anger in palliative care: a clinical approach.
AB  - Anger in patients and families is a common problem in the care of persons with
      advanced disease. Whereas it is widely accepted that anger may be a justifiable
      reaction to significant illness and loss, it frequently creates difficulties for
      the doctors involved in care. In particular, there is often a personal impact on
      the doctor at whom anger is directed. This paper examines results of qualitative
      research with palliative care workers in the context of the broader published
      literature and the authors' clinical experiences. The ability to interact
      effectively with angry patients is a skill that is often learned with experience
      and is extremely useful in both transforming the patients' reaction into a more
      creative emotion and in developing a therapeutic relationship. Despite
      conscientious efforts, however, a few patients continue to be angry. A practical
      approach to anger, useful for the clinician directly involved in care, is
      outlined along with some strategies to adopt in the face of persistent anger.

PMID- 17199846
TI  - Characteristics and outcome of type 2 diabetes in urban Aboriginal people: the
      Fremantle Diabetes Study.
AB  - We analysed data from Aboriginal patients with type 2 diabetes recruited to the
      community-based Fremantle Diabetes Study and compared them with those from the
      Anglo-Celt participants. Diabetes prevalence among Aboriginal people in the
      Fremantle area was more than double that of Anglo-Celts and the average age at
      diagnosis was 14 years or younger. Glycaemic control, urinary albumin :creatinine
      and the proportion of smokers were all higher in the Aboriginal group and there
      was evidence of lower diabetes-related quality of life and high rates of
      disability at a young age. The Aboriginal patients died 18 years or younger than
      their Anglo-Celt counterparts. Specialized, culturally-sensitive and sustainable
      programmes are urgently needed to improve the management of diabetes in urban
      Aboriginal communities.

PMID- 17199845
TI  - Mycophenolate mofetil substitution for cyclosporine-dependent myasthenia gravis
      and nephrotoxicity.
AB  - Severe autoimmune myasthenia gravis is difficult to manage and may require
      immunosuppression with cyclosporine. However, cyclosporine dependency is
      associated with the risk of nephrotoxicity. Mycophenolate mofetil is a non
      nephrotoxic alternative which should be considered to rescue cyclosporine
      dependent, severe myasthenia gravis sufferers with renal impairment from
      progression to end-stage renal failure. However, the evidence is limited and
      studies have not assessed the outcome of a direct substitution in these
      cyclosporine-dependent patients. We study three such patients who successfully
      converted to mycophenolate mofetil, and briefly examine the evidence behind this
      option. We believe that total cyclosporine withdrawal is feasible, but strongly
      recommend overlapping mycophenolate mofetil treatment with cyclosporine.

PMID- 17199847
TI  - How deep a superficial gravity abscess?

PMID- 17199849
TI  - Tornwaldt's cysts are sometimes a bit of a headache.

PMID- 17199848
TI  - Lane-Hamilton syndrome: simultaneous occurrence of coeliac disease and idiopathic
      pulmonary haemosiderosis.

PMID- 17199851
TI  - Complete heart block: Henoch-Schonlein purpura or Lyme carditis?

PMID- 17199854
TI  - The efficacy and safety of laparoscopic nephrectomy in patients with three or
      more comorbidities.
AB  - OBJECTIVES: Laparoscopic surgery for kidney treatment is a common procedure.
      However, the efficacy of this procedure in patients with several comorbidities
      has not been well investigated. We conducted a retrospective comparison of
      results of laparoscopic surgery between patients with several comorbidities and
      patients with no comorbidity to access the efficacy and safety of this procedure.
      METHODS: The subjects were 20 patients with three or more comorbidities (group A)
      and 46 patients with less than three comorbidities (group B). These 66 patients
      were 48 men and 18 women with a mean age of 62.3 years (age range, 24-83 years).
      The data from these two groups were compared for American Society of
      Anesthesiology (ASA) physical status score, previous surgical history, duration
      of surgery, estimated blood loss, tumor size, complications during and after
      surgery, conversion rates, time to oral intake, and length of hospital stay.
      RESULTS: The initial ASA score and age were significantly higher for the patients
      with comorbidities (P < 0.0001, P = 0.0008, respectively). All other variables
      before, during, and after surgery were similar for both laparoscopic groups.
      However, the incidence of atelectasis of laparoscopy was higher than that of open
      surgery. CONCLUSIONS: Laparoscopic nephrectomy for patients with comorbidities is
      safe and minimally invasive. Further investigation to prevent atelectasis is
      necessary.

PMID- 17199853
TI  - Estrogens and aspects of prostate disease.
AB  - Estrogens have long been associated with the processes involved in prostate
      carcinogenesis, particularly in cancer suppression. However, the synergistic
      influence of low concentrations of estrogens, together with androgens, in
      promoting aberrant growth of the gland has also been recognized. As new insights
      into the complex molecular events implicated in growth regulation of the prostate
      are revealed, the role of the estrogens has become clearer. The present review
      considers this role in relation to the pathogenesis of prostate cancer and the
      potential cancer-repressive influence of the dietary estrogens.

PMID- 17199856
TI  - Evaluation of regional lymph node dissection in patients with upper urinary tract
      urothelial cancer.
AB  - OBJECTIVE: The role of the lymph node dissection (LND) in conjunction with
      nephroureterectomy (NU) in upper tract urothelial cell carcinoma (UT-UCC) remains
      undefined. We evaluated the manner in which the LND was applied at NU, the
      patterns of lymph node (LN) involvement and the preoperative variables that could
      identify patients at high risk for lymph node metastasis (LNM). METHODS: We
      examined clinical, radiological and pathological records of patients who
      underwent NU for UT-UCC between 1985 and 2004. The central pathology laboratory
      reviewed all specimens and graded tumors using the 2002 World Health
      Organization/International Society of Urologic Pathologists grading system.
      RESULTS: Of the NU performed in 252 patients for UT-UCC, 105 (42%) were N0, 28
      (11%) N+ and 119 (47%) Nx. Some form of LN resection was performed with NU in 53%
      of patients, with a median of four LN sampled (interquartile range, 2-10). After
      adjustment for tumor and patient characteristics, surgeon remained a significant
      predictor of LN resection (P < 0.0005). Of the evaluated variables, suspicious LN
      on preoperative computed tomography, present in 60% of N+ patients, was the only
      preoperative variable associated with the pathological finding of LNM (P <
      0.0005). CONCLUSIONS: LND in patients with UT-UCC is surgeon-dependent. Given the
      prognostic importance of LN status and the limited accuracy of preoperative
      staging of the regional LN, surgeons should perform a regional LND at the time of
      NU.

PMID- 17199855
TI  - Clinical presentation of epithelioid angiomyolipoma.
AB  - OBJECTIVE: Epithelioid angiomyolipomas (AML) of the kidney are malignant tumors
      with aggressive clinical behavior. METHODS: We reviewed cases of epithelioid AML
      recently diagnosed at our institution to highlight the spectrum of clinical
      presentations. RESULTS: In all cases, renal lesions seen on computed tomography
      were suspicious for renal cell carcinoma (RCC). Histologically, these tumors can
      resemble RCC. The diagnosis of epithelioid AML was established by positive
      staining for melanoma and smooth muscle cell markers, and presence of
      perivascular epithelioid cells. One patient presented with a renal tumor
      extending into the inferior vena cava to the level of the hepatic veins. Two
      patients developed recurrent, metastatic disease following nephrectomy. One
      patient with tuberous sclerosis and multiple, bilateral AML developed an
      enhancing renal tumor that did not contain any fat densities. A partial
      nephrectomy was performed and pathology revealed epithelioid AML adjacent to
      conventional AML. CONCLUSIONS: These tumors are distinguished from RCC by
      positive immunostaining for melanoma markers and smooth muscle cell markers. They
      resemble conventional RCC on imaging. Epithelioid AML may be locally aggressive
      and metastasize.

PMID- 17199857
TI  - Location of spina bifida occulta and ultrasonographic bladder abnormalities
      predict the outcome of treatment for primary nocturnal enuresis in children.
AB  - OBJECTIVE: We examined whether the existence of spina bifida occulta or
      ultrasonographic bladder abnormalities was related to the outcome of treatment
      for primary nocturnal enuresis in children. METHODS: Between April 1996 and
      September 2005, a total of 77 subjects (53 boys and 24 girls, aged 5-18 years;
      mean age, 9.9 years) with primary nocturnal enuresis were studied. Plain X-ray
      films of the spine and ultrasonographic bladder measurements (bladder wall
      thickness, bladder neck descent and bladder neck opening) were obtained and the
      correlations with the outcome of treatment using imipramine hydrochloride were
      assessed. RESULTS: On plain X-ray films of the spine, spina bifida occulta
      (lumbar vertebrae in three, lumbosacral vertebrae in 19 and sacral vertebrae in
      31) was recognized in 53 children (69%). Ultrasonographic bladder abnormalities
      were recognized in 40 children (52%). Children with lumbar and lumbosacral spina
      bifida occulta showed a higher rate of concomitant ultrasonographic bladder
      abnormalities (P = 0.006) and had a poorer response to treatment (P = 0.041)
      compared with the children who had sacral spina bifida occulta. Children with
      ultrasonographic bladder abnormalities had a worse response to treatment (P =
      0.005) compared to the children without bladder abnormalities. CONCLUSIONS: The
      presence of lumbar spina bifida occulta and ultrasonographic bladder
      abnormalities was related to the outcome of treatment for primary nocturnal
      enuresis in children, suggesting that spinal radiography and vesical
      ultrasonography may be useful predictive tests.

PMID- 17199858
TI  - System for simultaneous detection of 16 pathogens related to urethritis to
      diagnose mixed infection.
AB  - OBJECTIVE: Urethritis is not always caused by a single pathogen, and isolation of
      more than two pathogens from one patient is not uncommon. We developed a method
      to simultaneously detect 16 pathogens related to urethritis. METHODS: We designed
      specific primers used for amplification of urethritis pathogens in our 16-well
      microplate assay. Sixteen microliters of each reaction mixture containing
      template DNA was added to each well to amplify 16 pathogens simultaneously.
      RESULTS: After we evaluated the specificity and sensitivity of this microplate
      polymerase chain reaction method, we used it to detect pathogens in clinical
      samples. Of 163 clinical samples, 49.7% (81/163) were positive for specific
      pathogens, and 6.7% (11/163) showed mixed infection. A specific pathogen was not
      identified in 43.6% (71/163) of cases. CONCLUSIONS: We developed a 16-well
      microplate assay with 16 specific primers to identify pathogens associated with
      urethritis.

PMID- 17199859
TI  - Dorsal inlay graft urethroplasty for primary hypospadiac repair.
AB  - OBJECTIVE: Tubularized incised plate urethroplasty has become a popular technique
      for repairing distal and proximal hypospadias in many institutions. Dorsal inlay
      graft urethroplasty has been used in our institution since 2003 to reduce the
      risk of meatal stenosis. In the present study, we evaluated the results of the
      dorsal inlay graft procedure. METHODS: A total of 28 patients with no deep groove
      and no severe curvature underwent one-stage urethroplasty using an inner
      preputial-based dorsal inlay graft. The medical records of all patients were
      retrospectively reviewed with regard to complication rate and cosmetic
      appearance. RESULTS: Mean patient age at surgery was 21 months (range, 14 months
      to 4.6 years). Preoperatively the urethral meatus was coronal in two cases,
      distal shaft in 17, proximal shaft in six and penoscrotal in three. Nine patients
      required testosterone therapy before surgery. Mean operative time was 200 min
      (range, 154-249 min). Mean length of inlay graft was 20.9 mm (range, 12-30 mm).
      In all patients, a straight penis was achieved without dorsal plication of the
      corposa cavernosa, and the neomeatus with a slit-like appearance was positioned
      at the glans tip. At a mean of 22 months of follow up, a urethrocutaneous fistula
      developed in only one patient (3.6%), requiring repair surgery 6 months after
      urethroplasty. No patient had meatal stenosis, neourethral stricture or urethral
      diverticulum along the inlay graft. CONCLUSION: Dorsal inlay graft urethroplasty
      is an effective method for hypospadiac repair and leads to good cosmetic outcome
      with low risk of complications.

PMID- 17199860
TI  - Severity of erectile dysfunction in married impotent patients: interrelationship
      with anthropometry, hormones, metabolic profiles and lifestyle.
AB  - OBJECTIVE: This study was designed to evaluate the effects of risk factors for
      erectile dysfunction (ED) or cardiovascular disease on the disease severity in
      impotent men. METHODS: A total of 87 men, 25-75 years old (mean age, 53.4) were
      included in the study. Patients were evaluated with anthropometry, hormones,
      metabolic profiles and lifestyle. Baseline erectile function (EF) was evaluated
      using the International Index of Erectile Function (IIEF). The severity of ED was
      classified into the following four grades based on the six-item EF domain of the
      IIEF: severe (6-10); moderate (11-16); mild to moderate (17-21); and mild (22
      25). Patients were deemed to have metabolic syndrome (MS) if they had three or
      more of five criteria according to National Cholesterol Education Program, with
      some modification. RESULTS: Of 87 patients, 15 patients (17.2%) had mild, 11
      (12.6%) had mild to moderate, 33 (37.9%) had moderate and 28 (32.3%) had severe
      ED. There was no correlation between scores of IIEF or EF domain and continuous
      parameters. On the multivariate model used, hypertensive patients had 26-fold
      higher risk (odds ratio, 26.195; 95% confidence interval, 1.463-46.072; P =
      0.027) of severe ED than those without hypertension. Other factors were not
      significant. CONCLUSION: The results of the study indicate that MS might not
      influence the severity of ED in impotent men. However, our findings suggest that
      hypertension plays a role in the disease severity in these patients.

PMID- 17199861
TI  - Long-term results of first-line sequential high-dose carboplatin, etoposide and
      ifosfamide chemotherapy with peripheral blood stem cell support for patients with
      advanced testicular germ cell tumor.
AB  - OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in
      patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose
      chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide,
      ifosfamide chemotherapy followed by autologous peripheral blood stem cell
      transplantation (PBSCT) was investigated as first-line chemotherapy in patients
      with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular
      GCT patients with Indiana 'advanced disease' criteria received three cycles of
      bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus
      PBSCT, if elevated serum tumor markers were observed after three cycles of the
      BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the
      tumor marker(s) declined to normal range. Twenty-five patients received BEP and
      HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and
      25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and
      marker-positive partial responses, respectively. The other patients achieved no
      change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median
      follow-up time of 54 months. Severe toxicity included treatment-related death
      (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully
      applied in a multicenter setting. HD-CT demonstrated modest anticancer activity
      for Japanese patients with advanced testicular GCT and was well tolerated. This
      regimen might be examined for further investigation in randomized trials in first
      line chemotherapy for patients with poor-risk testicular GCT.

PMID- 17199862
TI  - Chronic acid ingestion promotes renal stone formation in rats treated with
      vitamin D3.
AB  - OBJECTIVE: Although hypercalciuria, a well-established adverse effect of vitamin
      D3, can be a risk factor of renal stone formation, the risk of nephrolithiasis
      has not been well defined. The consumption of a diet high in acid precursors is
      often cited as a risk factor for the development of calcium-based kidney stones.
      In the present study, we investigated the effect of chronic acid ingestion on
      kidney stone formation in rats treated with calcitriol (1-25[OH]2 D3). METHODS:
      Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 microg
      of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl),
      calcitriol-treated (three treatments of 0.5 microg of calcitriol per week) rats
      (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone
      samples were analyzed. RESULTS: The A-V rats exhibited elevated serum calcium
      concentrations, urinary calcium and phosphate excretion, urinary type I collagen
      cross-linked N-peptide (NTx)/creatinine values, mRNA expression of osteopontin in
      the kidney, and renal calcium contents as well as decreased bone mineral
      densities, compared with the C-C and C-V rats. Urinary citrate excretion was
      lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in
      the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats.
      CONCLUSIONS: The ingestion of NH4Cl, an acid precursor, promotes calcium
      phosphate kidney stone formation in calcitriol-treated rats. The chronic intake
      of a diet rich in acid precursors may be a risk factor for the development of
      kidney stones in subjects who are being treated with calcitriol.

PMID- 17199864
TI  - Two von Recklinghausen's disease cases with pheochromocytomas and
      gastrointestinal stromal tumors (GIST) in combination.
AB  - We here document two cases of von Recklinghausen's disease with both
      pheochromocytomas and gastrointestinal stromal tumors (GIST). It is very rare
      that these three disorders are found to occur simultaneously, although the fact
      that preoperative detection of GIST is difficult except with large tumors may be
      important in this respect. In the present cases, GIST were not evident on
      preoperative computed tomography and magnetic resonance imaging, and were
      identified unexpectedly during surgery. Our findings indicate that investigation
      of the intraperitoneal space should be performed during adrenalectomy for
      pheochromocytomas with von Recklinghausen's disease.

PMID- 17199863
TI  - Influence for testicular development and histological peculiarity in the testes
      of flutamide-induced cryptorchid rat model.
AB  - OBJECTIVES: To investigate influence for the testicular development and to assess
      the usefulness as an animal model, cryptorchid rats were induced by exposure to
      flutamide during the fetal period and their testes examined histologically.
      METHODS: Flutamide was injected into the abdomen of pregnant rats for 7 days from
      the 14th to 20th day of gestation. The male offspring in which cryptorchidism was
      observed at 28 days after birth were defined as the model rats. They were divided
      into four groups by dosage of flutamide (2.5 mg, 5 mg, 7.5 mg, 15 mg per day),
      and their testicular weight, spermatogenesis (modified Johnsen score), and germ
      cell apoptosis were examined histochemically at 10 weeks after birth. RESULTS:
      The incidence of cryptorchidism including both unilateral and bilateral in the
      2.5, 5, 7.5 and 15-mg flutamide groups was 58.3%, 81.9%, 93.6% and 91.0%,
      respectively. In the model rats, the undescended testes were located at the
      caudal end of the abdominal cavity, and these testes weighed less than the contra
      descended testes in each group. Histologically, apoptotic cells were markedly
      increased, the seminiferous tubules were degenerated and disturbance of spermatid
      differentiation was observed in the undescended testes compared with the normal
      or contra-lateral descended testes. CONCLUSIONS: We found out that the incidence
      of undescended testes increased in a flutamide dose-dependent manner. The
      findings of histological examination were independent of the administrated dose
      of flutamide and it is suggested that exposure of the testes to abdominal
      temperature causes spermatogenic arrest with germ cell apoptosis. The present
      animal model indicates high incidence of above 90%, has no surgical stress and
      dose not require special techniques. We believe that the present model is a
      useful tool for the understanding of pathogenesis and treatment of cryptorchidism
      and further biological research into spermatogenesis.

PMID- 17199865
TI  - Spontaneous disappearance of multiple lung metastases after nephroureterectomy
      from sarcomatoid carcinoma of the renal pelvis: a case report.
AB  - We report a case in which lung metastases disappeared spontaneously after
      nephroureterectomy from sarcomatoid carcinoma of the renal pelvis. A 58-year-old
      man presented with gross hematuria. Computed tomography (CT) revealed a left
      renal tumor and multiple lung metastases. Intravenous pyelography revealed a
      filling defect in the upper renal calyx. Urine cytology was positive. Left renal
      pelvic cancer was diagnosed and nephroureterectomy performed. The resected
      specimen was diagnosed pathologically as sarcomatoid carcinoma of the renal
      pelvis. Approximately 5 months later, CT revealed that the lung metastases had
      disappeared. There has been no evidence of disease for 46 months postoperatively.

PMID- 17199866
TI  - Case of carcinosarcoma of urinary bladder obtained a pathologically complete
      response by neoadjuvant chemoradiotherapy.
AB  - Carcinosarcoma of the bladder is an unusual malignancy characterized by an
      intimate admixture of malignant epithelial elements (carcinoma) and malignant
      soft tissue elements (sarcoma). To our knowledge, almost 80 cases have been
      reported, usually as case reports or small series. Patient with carcinosarcoma
      usually present with a high stage malignancy. Cystectomy or transurethral
      resection is the preferred treatment, often followed by radiation therapy,
      although prognosis is very bad. We herein report a case of carcinosarcoma of
      bladder obtained pathologically complete response by neoadjuvant
      chemoradiotherapy. She now shows no evidence of disease 30 months after the
      operation. To our knowledge, it is the first case where urinary bladder
      carcinosarcoma obtained a pathologically complete response by chemoradiotherapy.

PMID- 17199868
TI  - Testicular seminoma occurring 8 years after treatment of a metastatic
      extragonadal germ cell tumor.
AB  - A 30-year-old man was admitted with a chief complaint of left-sided scrotal
      enlargement, and was diagnosed as having testicular seminoma after orchiectomy.
      Eight years earlier, he had been treated with chemotherapy for an extragonadal
      germ cell tumor, without orchiectomy, leading to complete remission. His
      histological diagnosis at that time was a germ cell tumor, composed of
      choriocarcinoma and embryonal carcinoma. He was followed up without testicular
      biopsy. Routine pretreatment testicular biopsy in patients with extragonadal germ
      cell tumor is controversial, but regular long-term follow up and information on
      the risk of developing a metachronous testicular tumor are needed after treatment
      of extragonadal germ cell tumors, even when there seems to be a partial or
      complete clinical response.

PMID- 17199867
TI  - Effect of zoledronic acid on metastatic hormone-refractory prostate cancer
      resistant to taxane, estramustine, carboplatin, and dexamethasone.
AB  - This case report demonstrates the effect of zoledronic acid (ZA) on a patient
      with bone metastatic hormone-refractory prostate cancer (HRPC) resistant to
      taxane, estramustine phosphate, carboplatin, and dexamethasone. The pathogenesis,
      diagnosis, and management of bone metastasis on HRPC are also reviewed.

PMID- 17199869
TI  - Intrascrotal involvement of sarcoidosis presenting like testicular appendices.
AB  - A 31-year-old male visited our clinic with a complaint of painless intrascrotal
      mass in the left side. He had been diagnosed with pulmonary sarcoidosis 6 years
      prior. Scrotal ultrasound revealed a distinct mass measuring 18 mm x 16 mm at the
      left epididymal tail. An epididymectomy was performed for treatment and
      pathological diagnosis. Four nodules shaped like testicular appendices were also
      found on the testicular surface and subsequently removed. Histopathological
      examination established that both the epididymal and appendix-like lesions
      consisted of non-caseating epithelioid granulomas with giant cells, and were
      diagnosed as sarcoidosis. The patient has no recurrence of intrascrotal lesions
      after 6-month follow up. This is the first report of intrascrotal involvement of
      sarcoidosis presenting like testicular appendices.

PMID- 17199870
TI  - Function of cardiac M3 receptors.
AB  - 1. Since the initial identification of the M3 subtype of muscarinic acetylcholine
      receptors (M3-mAChR) in the heart, there have been increasing interest and
      advances in studies on the pathophysiological roles of M3-mAChR in the heart.
      Recent studies from several laboratories have provided compelling and solid
      evidence in support of the important roles of M3-mAChR in regulation and
      maintenance of cardiac function and in generation and progression of heart
      disease as well. 2. The functions of the cardiac M3-mAChR revealed thus far
      include (i) M3-mAChR regulation of heart rate and cardiac repolarization, (ii)
      modulation of inotropic effects, (iii) cytoprotection against ischaemic injuries
      of myocardium, (iv) regulation of cell-to-cell communication, and (v)
      participation in generation and maintenance of atrial fibrillation. 3. Signal
      transduction mechanisms underlying these pathophysiological functions have also
      been studied, which have allowed us to get insight into the following mechanistic
      aspects. (i) M3-mAChR activates a delayed rectifying K+ current I(KM3) to
      participate in cardiac repolarization, negative chronotropic actions, and anti
      dysrhythmic (suppresses ischaemic dysrhythmias) as well as pro-dysrhythmic
      (facilitates atrial fibrillation) actions. (ii) M3-mAChR interacts with gap
      junctional channel connexin 43 to maintain cell-cell communication and excitation
      propagation. (iii) M3-mAChR regulates intracellular phosphoinositide hydrolysis
      to improve cardiac contraction and haemodynamic function. (iv) M3-mAChR activate
      anti-apoptotic signalling molecules, enhances endogenous antioxidant capacity,
      and diminishes intracellular Ca2+ overload, all of which contribute to protecting
      the heart against ischaemic injuries. 4. This article provides an overview of the
      potential roles of the M3-mAChR in parasympathetic control of heart function
      under normal physiological conditions and in the setting of a variety of
      pathological processes including heart failure, myocardial ischaemia and
      dysrhythmias.

PMID- 17199871
TI  - Potential antioxidant activity of celecoxib and amtolmetin guacyl: in vitro
      studies.
AB  - 1. In vitro studies of the potential antioxidant activity of the selective cyclo
      oxygenase-2 inhibitor celecoxib and the non-steroid anti-inflammatory drug
      amtolmetin guacyl (AMG) were carried out. The study included experiments on the
      ability of these drugs to affect some indices of the oxidative stress [lipid
      peroxidation (LP), activity of antioxidant enzymes, glutathione (GSH) level] in
      rat stomach and colon mucosa and in liver. 2. Celecoxib and AMG did not change
      the activity of the enzymes GSH-peroxidase, oxidased glutathione (GSSG)-reductase
      and glucose-6-phosphate-dehydrogenase, as well as the GSH level in all tissue
      preparations. An increased superoxide dismutase (SOD) activity and a tendency to
      a decreased Fe/ascorbic acid-induced LP in stomach and colon mucosa were found,
      but only in the presence of AMG. 3. In the liver, both celecoxib and AMG
      decreased spontaneous and Fe/ascorbic acid-induced LP. SOD activity was enhanced
      only in the presence of AMG. 4. Experiments aimed at studying celecoxib and AMG
      in free oxygen radical-generating systems were also carried out. AMG and tolmetin
      (the main metabolite of AMG) inhibited OH*-provoked deoxyribose degradation in a
      Fenton system. Celecoxib had no effect on free radicals when tested in the same
      system. 5. In conclusion, the results of the present in vitro studies suggest
      that AMG and celecoxib possess antioxidant and metal-chelating abilities, which
      might contribute to their beneficial effects.

PMID- 17199872
TI  - Vascular alpha1-adrenoceptors in isolated perfused rat kidney: influence of
      ageing.
AB  - 1. The present study identifies alpha1-adrenoceptor subtype(s) involved in
      constrictor responses of the kidney and how ageing influences it. 2. The study
      was conducted on kidneys from F344BNF1 rats, which unlike F344 or Wistar rats
      used by many previous investigators do not exhibit glomerulonephritis at advanced
      age. 3. Noradrenaline (NA) and phenylephrine (PHE) (non-selective alpha1) and
      A61063 (selective alpha(1A)) adrenoceptor agonists elicited constriction of
      perfused kidneys of young and old rats. The pD2 values (index of renovascular
      reactivity) were significantly higher for A61603 than for either PHE or NA, and
      significantly decrease across age groups. 4. BMY 7378 or RS 100329, alpha(1D)- or
      alpha(1A)-adrenoceptor antagonists, respectively antagonized the constrictor
      responses and suppressed the maximal responses to all agonists in young adult rat
      kidneys. However, antagonism of PHE or A61063 by BMY 7378 in old rat kidneys was
      surmountable. 5. This study suggests that: (i) alpha(1A) and alpha(1D)
      adrenoceptor subtypes mediate vasoconstriction of perfused rat kidney; (ii)
      alpha(1A)-adrenoceptor subtype appears to predominate in renal vasculature based
      on agonist relative potencies. (iii) Ageing significantly decreases alpha1
      adrenoceptor-mediated vasoconstriction of rat kidney.

PMID- 17199873
TI  - Exogenous purines induce differential responses in the proximal and distal
      regions of the possum sphincter of Oddi.
AB  - 1. The aim of this study was to compare the effect of exogenous ATP and adenosine
      on spontaneous motility of the proximal and distal regions of the possum
      sphincter of Oddi (SO). 2. ATP or adenosine (1 microm-1 mm) was applied to distal
      SO or proximal-SO muscle rings in organ baths in the absence or presence of
      tetrodotoxin (TTX) or P1/P2 antagonists. 3. Both ATP and adenosine altered
      spontaneous activity, predominantly in proximal-SO rings. 4. Exogenous ATP
      induced a bi-phasic response consisting of a brief TTX-sensitive excitatory
      component, and a longer-lasting TTX-insensitive inhibitory component. 5. The
      excitatory ATP response likely involves P2X receptors, whereas the late
      inhibitory response likely involves P2Y receptors. 6. Exogenous adenosine
      decreased spontaneous SO activity, via a TTX-insensitive mechanism. 7. Exogenous
      purines modulate SO motility, acting primarily in the proximal region of the SO,
      via neural and non-neural mechanisms and multiple purine receptor subtypes.

PMID- 17199874
TI  - Heterogeneous effect of leucotriene CysLT1 receptor antagonists on antigen
      induced motor and inflammatory responses in guinea-pig airways.
AB  - 1. The effect of montelukast or MEN91507, selective leucotriene CysLT1 receptor
      antagonists, on antigen-induced airway inflammation and bronchoconstriction were
      compared in anaesthetized guinea-pigs. 2. In sensitized animals, ovalbumin (0.3
      mg kg(-1), i.v.)-induced microvascular leakage in trachea, intrapulmonary
      airways, total lung (parenchyma and intrapulmonary airways) and urinary bladder
      was reduced by MEN91507 (0.01-1 micromol kg(-1), i.v.), whereas montelukast (0.01
      1 micromol kg(-1), i.v.) antagonized the effect of the antigen only in the lung
      and urinary bladder. 3. Ovalbumin (1 mg kg(-1), i.v.)-induced bronchoconstriction
      was dose dependently antagonized by MEN91507 (10-30 micromol kg(-1), i.v.),
      whereas the effect of montelukast (0.1-30 micromol kg(-1), i.v.) was marginal (15
      30% inhibition). Neither MEN91507 nor montelukast (30 micromol kg(-1), i.v.)
      affected the bronchoconstrictor response induced by acetylcholine (0.3 micromol
      kg(-1), i.v.) in sensitized animals. 4. It is concluded that montelukast and
      MEN91507 display a differential activity against the effect of endogenous
      leucotrienes, despite the fact that both compounds show a similar antagonist
      profile against exogenous leucotrienes acting through CysLT1 receptors.

PMID- 17199875
TI  - Effect of short-term outlet obstruction on rat bladder nerve density and
      contractility.
AB  - 1 The present study was designed to investigate the relationship between
      innervation density and contractile responses to field stimulation and exogenous
      agonists at early time points after induction of bladder outlet obstruction (BOO)
      in rats. 2 When compared with sham-operated animals, 1, 3 and 7 days of BOO were
      associated with a 75%, 80% and 90% increase of bladder weight. Field stimulation
      caused a frequency-dependent increase in force of contraction. The force of
      contraction was reduced at each frequency in BOO rats with the greatest decrease
      after 1 day and a gradual but incomplete recovery thereafter. In contrast,
      contractile responses to ATP, carbachol and KCl were markedly reduced after 1 day
      of BOO and fully recovered after 7 days. The neurofilament staining was not
      altered by 1 day of BOO, but gradually decreased with increasing duration of BOO
      reaching the lowest levels after 7 days. 3 We conclude that impaired cellular
      contractility seems to underlie the early reductions of field stimulation-induced
      contraction, possibly reflecting surgical trauma of the tissue. However, at later
      time points a reduced nerve density, possibly reflecting a partial denervation,
      appears to be the main reason for impaired contractile response to field
      stimulation.

PMID- 17199876
TI  - Contractile activity of ATP and diadenosine tetraphosphate on urinary bladder in
      the rat: role of A1- and P2X-purinoceptors and nitric oxide.
AB  - 1. Both adenosine-5'-triphosphate (ATP) and diadenosine tetraphosphate (AP4A)
      produced a dose-dependent contraction of the isolated rat urinary bladder rings.
      AP(4)A dose-response curve was to the left of that of ATP, and maximum response
      was greater than that produced by ATP. 2. 8-cyclopentyl-1,3-dipropylxanthine
      (DPCPX), the A1-purinergic receptor blocker (0.01 mm) significantly inhibited the
      ATP- and AP4A-induced contractions at the whole dose range. The inhibition was
      between 31-41%, and 15-25% for ATP and AP4A respectively. 3. Pyridoxal phosphate
      6-azophenyl-2',4'-disulphonic acid (PPADS), the P2X-purinoceptor antagonist (0.01
      mm) potently inhibited the bladder contractions in response to ATP and AP4A by
      around 75-80%. 4. The nitric oxide (NO) precursor L-arginine reduced the bladder
      contractile response to ATP by about 22-41% and that of AP4A to a lesser extent
      by around 20-32%. 5. The nitric oxide synthase inhibitor, N(G)-nitro-L-arginine
      methyl ester (L-NAME, 0.1 mM), did not produce any significant effect on ATP
      except for a weak inhibition of about 14% at the lowest dose of ATP. The
      contractions in response to AP4A were only slightly reduced by L-NAME by about
      20%. 6. In conclusion, the contractile response of the bladder to ATP and to the
      dinucleotide AP4A is mediated mainly through P2X-purinoceptors and A1-purinergic
      receptors. In the detrusor muscle, NO donation possesses an inhibitory effect on
      ATP-mediated contractility more than that produced by the dinucleotide AP4A.

PMID- 17199877
TI  - In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant
      defence systems in different models of gastrointestinal injury.
AB  - 1. The in vivo effects of the non-steroid anti-inflammatory drug (NSAID)
      amtolmetin guacyl (AMG) on lipid peroxidation (LP) and on antioxidant enzyme and
      non-enzyme defence systems were investigated in models of stomach and colon
      damages, induced by other NSAIDs, by ethanol or by 2,4,6-trinitrobenzenesulfonic
      acid (TNBS). 2. Indomethacin increased LP, glutathione peroxidase (GSH-PX) and
      glucose-6-phosphate dehydrogenase (Glu-6-P-DH) activities and decreased
      glutathione levels in gastric mucosa. Pretreatment with AMG normalized some of
      the parameters affected by indomethacin. 3. Treatment of rats with ethanol for
      0.5 h led to a decrease in glutathione levels as well as activities of
      glutathione reductase and Glu-6-P-DH in gastric mucosa. AMG, administered 0.5 h
      before ethanol, limited the adverse actions of ethanol. 4. Amtolmetin guacyl
      failed to abolish the TNBS-induced changes in the followed-up parameters in colon
      mucosa and liver, but additional alterations (as with tolmetin) were not
      observed. 5. The beneficial profile of AMG in the various experimental models of
      free radical-induced damage investigated in this study suggests the possibility
      that this drug might possess antioxidant activity.

PMID- 17199878
TI  - The classical competitive antagonism of phentolamine on smooth muscle
      preparations, investigated by two procedures.
AB  - 1. In isolated smooth muscle tissues taken from rats, rabbits and guinea-pigs,
      all at 37.5 degrees C, the equilibrium dissociation constant (K(beta)) of the
      competitive, reversible alpha-adrenoceptor antagonist phentolamine varied between
      4 and 28 nm. 2. The concentration of the antagonist required to inhibit
      contractions to direct- or indirect-acting alpha-adrenenoceptor agonists by 50%
      (IC50) also varied between 5 and 30 nm. 3. From one tissue to another, the
      IC50/K(beta) ratio of the blocker varied from 1 to 2.5, the values being close to
      those predicted by classical receptor theory based on the law of mass action. 4.
      At 27.5 degrees C, using phenylephrine as the spasmogen in rat aorta, the
      IC50/K(beta) ratio for phentolamine was 3.1. 5. A significantly higher IC50
      compared with K(beta) for phentolamine indicates that the procedures for
      estimating affinity constants for a competitive antagonist are not equivalent.

PMID- 17199881
TI  - Successful treatment by double filtrate plasmapheresis in a pregnant woman with
      the rare P blood group and a history of multiple early miscarriages.
AB  - Individuals of P type, a rare blood group, have anti-PP(1)P(k) antibody in their
      serum, which causes spontaneous abortion in the early stages. We report a patient
      of p type suffering from multiple spontaneous abortions. We also review
      previously reported cases from published work. A 36-year-old woman (gravida 2,
      para 0) was referred to our hospital because of habitual abortion. At the third
      pregnancy, we started double filtration plasmapheresis (DFPP) from 7 weeks 3 days
      to remove the antibody. We attained rapid decline in the titer and normal fetal
      growth. Gradual tapering of the DFPP frequency caused neither a rebound of the
      titer nor growth retardation. During the course, she experienced only one episode
      of catheter infection as an adverse effect. At 37 weeks 3 days, after 57 DFPP
      repetitions, a 2496 g girl was delivered by cesarean section. The infant suffered
      neither from anemia nor from severe jaundice. A review of previous reports
      indicates that the titer of the pathogenic antibody should be kept as low as
      possible from the early gestational stage in P-incompatible habitual abortion
      cases, otherwise the case typically comes to an unfavorable outcome. Plasma
      exchanges with fresh plasma potentially induce contamination by either known or
      unknown pathogens. Such risks are reduced using DFPP because the volume of
      albumin solution that replaces fresh plasma is less than that by plasma exchange.
      The present case, along with previous reports, shows that DFPP is an effective
      therapy for treating P-incompatible pregnancy.

PMID- 17199880
TI  - An overview of regular dialysis treatment in Japan (as of 31 December 2004).
AB  - A statistical survey of 3932 nationwide hemodialysis (hereafter, dialysis)
      facilities was carried out at the end of 2004, and 3882 facilities (98.73%)
      responded. The population undergoing dialysis at the end of 2004 was 248 166, an
      increase of 10 456 patients (4.4%) from that at the end of 2003. The number of
      dialysis patients per million people was 1943.5. The crude death rate of dialysis
      patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of
      patients who underwent dialysis in 2004 was 65.8 years, and that of the total
      dialysis population was 63.3 years. The percentage distribution of patients who
      underwent dialysis according to a newly underlying disease showed that 41.3% of
      patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The
      frequency of calcium carbonate use for dialysis patients was 75.1% and that of
      sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride
      use does not necessarily have a strong correlation with the dose of calcium
      carbonate. Patients who received high doses of sevelamer hydrochloride tended to
      have a low concentration of arterial blood HCO(3-). Approximately 15% of dialysis
      patients used an intravenous vitamin D preparation, generally maxacalcitol. The
      longer the patients had been on dialysis, the higher the frequency of use of an
      intravenous vitamin D preparation. When the concentration of serum intact
      parathyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an
      orally administered vitamin D preparation decreased; but that of intravenous
      vitamin D preparation increased. The percentage of dialysis patients who received
      percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more
      than 50% in the patients who had been on dialysis for more than 10 years. The
      percentage of patients who received PEIT again was 35.0%. The percentage of
      patients who had been on hemodialysis for more than 10 years and received PEIT
      again was more than 50%.

PMID- 17199882
TI  - Elimination of 2-arachidonoylglycerol action by direct hemoperfusion through
      immobilized polymyxin B fibers: an experimental study in conscious guinea pigs.
AB  - Direct hemoperfusion through a network of immobilized polymyxin B fibers is used
      for the treatment of septic shock, but the mechanism underlying the clinical
      benefits remains unclear. The aims of the present study were to assess the
      actions of direct hemoperfusion through immobilized polymyxin B fibers on effects
      of exogenous endotoxin or 2-arachidonoylglycerol in conscious guinea pigs; and to
      examine the underlying mechanisms. In the present study, colonic motion was
      monitored continuously by telemetry using a force transducer attached to the
      taenia caecum, while blood pressure was monitored with a carotid artery catheter.
      To establish a hemoperfusion circuit in a freely moving, conscious guinea pig,
      catheters were implanted in the carotid artery and the jugular vein, tunneled
      subcutaneously, exteriorized at the back of the neck in contact with a
      lightweight tethering spring, and attached to a swivel device at the top of the
      cage. On the day after the operation, lipopolysaccharide (Escherichia coli,
      O111:B4; 1 mg/kg) or 2-arachidonoylglycerol (1 mg/kg) was given intraperitoneally
      (i.p.) and direct hemoperfusion through immobilized polymyxin B fibers was
      carried out for 2 h. The results showed that in guinea pigs treated with direct
      hemoperfusion through immobilized polymyxin B fibers, relaxation of colonic
      longitudinal muscle caused by lipopolysaccharide or 2-arachidonoylglycerol was
      significantly suppressed, as were decreases in blood pressure. We conclude that
      the actions following exogenous administration of 2-arachidonoylglycerol were
      eliminated by direct hemoperfusion through immobilized polymyxin B fibers. These
      results suggest that effectiveness of direct hemoperfusion through immobilized
      polymyxin B fibers in endotoxemia involves elimination of 2-arachidonoylglycerol
      action.

PMID- 17199883
TI  - Improved coronary vasodilatatory capacity by H.E.L.P. apheresis: comparing
      initial and chronic treatment.
AB  - Hypercholesterolemia impairs endothelial function and subsequently decreases
      coronary vasodilatatory capacity. We examined the quantitative effects of one
      single LDL apheresis on vasodilatatory capacity. Using N-13 ammonia as a tracer
      for dynamic quantitative positron emission tomography (PET), mean myocardial
      perfusion measurements were carried out before and 20 h later after LDL
      apheresis, both under resting conditions and after pharmacological vasodilatation
      with dipyridamole. LDL apheresis was carried out using the heparin induced
      extracorporeal LDL precipitation (H.E.L.P.) procedure. We examined 47 patients
      (12 women and 35 men), with angiographically-proven coronary artery disease. All
      of them suffered from hypercholesterolemia. Of the patients, 35 received a
      chronic weekly H.E.L.P. procedure (group A), while H.E.L.P. procedure treatment
      was started for the first time in 12 patients, who were subsequently enrolled in
      a chronic apheresis program (group B). H.E.L.P. apheresis was combined with
      cholesterol lowering drugs in all patients. Both groups underwent positron
      emission tomography twice (prior to LDL apheresis and 20 h later). In group A,
      LDL cholesterol levels decreased from 175 +/- 50 mg/dL to 60 +/- 21 mg/dL
      immediately after H.E.L.P. (77 +/- 25 mg/dL before the second PET). Corresponding
      values for fibrinogen levels were 287 +/- 75 mg/dL to 102 +/- 29 mg/dL (155 +/-
      52 mg/dL), minimal coronary resistance dropped from 0.56 +/- 0.20 to 0.44 +/-
      0.17 mm Hg x 100 g x min/mL (P < 0.0001). Plasma viscosity decreased by 7.8%. In
      group B, LDL cholesterol decreased from 187 +/- 45 mg/dL to 75 +/- 27 mg/dL (85
      +/- 29 mg/dL) and fibrinogen from 348 +/- 65 mg/dL to 126 +/- 38 mg/dL (168 +/-
      45 mg/dL). Minimal coronary resistance was reduced from 0.61 +/- 0.23 to 0.53 +/-
      0.19 mm Hg x 100 g x min/mL (P < 0.01). Plasma viscosity was observed to decrease
      by 7.6%. The strong LDL drop in patients under chronic H.E.L.P. treatment has a
      significant impact on coronary vasodilatatory capacity within 20 h leading to an
      improved overall cardiac perfusion. Nearly the same effect can be seen in
      patients after their first H.E.L.P. treatment.

PMID- 17199885
TI  - Survival of adult neurons lacking cholesterol synthesis in vivo.
AB  - BACKGROUND: Cholesterol, an essential component of all mammalian plasma
      membranes, is highly enriched in the brain. Both during development and in the
      adult, brain cholesterol is derived from local cholesterol synthesis and not
      taken up from the circulation. However, the contribution of neurons and glial
      cells to total brain cholesterol metabolism is unknown. RESULTS: Using
      conditional gene inactivation in the mouse, we disrupted the squalene synthase
      gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule
      cells and some precerebellar nuclei. Mutant mice showed no histological signs of
      neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited
      normal motor coordination. This revealed that these adult neurons do not require
      cell-autonomous cholesterol synthesis for survival or function. CONCLUSION: We
      conclude that at least some adult neurons no longer require endogenous
      cholesterol synthesis and can fully meet their cholesterol needs by uptake from
      their surrounding. Glia are a likely source of cholesterol in the central nervous
      system.

PMID- 17199886
TI  - The value of health care--a matter of discussion in Germany.
AB  - BACKGROUND: Interest in assessing the value of health-care services in Germany
      has considerably increased since the foundation of the Institut fur Qualitat und
      Wirtschaftlichkeit im Gesundheitswesen, IQWiG (Institute for Quality and
      Efficiency in Health Care). The practical application of value assessment
      illustrates how problematic the process can be. In all decisions made for the
      provision of health care, data concerning the measurable dimensions (quantity and
      quality of efficacy and effectiveness, validity of the results and costs) flow
      into a complex and not yet standardized decision-making process concerning public
      financing. Some of these decisions are based on data of uncertain validity,
      unknown reproducibility and unclear appropriateness. DISCUSSION: In this paper we
      describe the theoretical aspects of value from psychological and economic
      viewpoints and discuss national and international approaches. Methodic details
      and difficulties in assessing the value of health-care services are analysed. A
      definition of the intangible value of health-care services will be proposed which
      contains only three factors: the absolute risk reduction (usually a measure of
      efficacy), the validity of the scientific papers examined and the type of the
      expected effectiveness (prevention of death and disability, restitution of well
      being). The intangible value describes the additional benefit when comparing two
      possible actions, like treatment or observation only. CONCLUSION: The description
      of intangible value from the viewpoint of different stakeholders is a useful
      measure for subsequent steps (not discussed here) - the evaluation of costs and
      of patient benefit. A standardised, transparent, fair and democratic evaluation
      is essential for the definition of a basic benefit package.

PMID- 17199887
TI  - Improving the quality and efficiency of follow-up after curative treatment for
      breast cancer--rationale and study design of the MaCare trial.
AB  - BACKGROUND: After curative treatment for breast cancer women frequently attend
      scheduled follow-up examinations. Usually the follow-up is most frequent in the
      first 2-3 years (2-4 times a year); thereafter the frequency is reduced to once a
      year in most countries. Its main aim is to detect local disease recurrence, or a
      second primary breast cancer, but also to provide information and psychosocial
      support. However, the cost-effectiveness of these frequent visits is under much
      debate, leading to a search for less intensive and more cost-effective follow-up
      strategies. In this paper the design of the MaCare trial is described. This trial
      compares the cost-effectiveness of four follow-up strategies for curatively
      treated breast cancer patients. We investigate the costs and effects of nurse-led
      telephone follow-up and a short educational group programme. METHODS/DESIGN: The
      MaCare trial is a multi centre randomised clinical trial in which 320 breast
      cancer patients are randomised into four follow-up strategies, focussed on the
      first 18 months after treatment: 1) standard follow-up; 2) nurse-led telephone
      follow-up; 3) arm 1 with the educational group programme; 4) arm 2 with the
      educational group programme. Data is collected at baseline and 3, 6, 12 and 18
      months after treatment. The primary endpoint of the trial is cancer-specific
      quality of life as measured by the global health/QoL scale of the EORTC QLQ-C30.
      Secondary outcomes are perceived feelings of control, anxiety, patients'
      satisfaction with follow-up and costs. A cost-effectiveness analysis will be
      performed from a societal perspective. DISCUSSION: Reduced follow-up strategies
      for breast cancer have not yet been widely applied in clinical practice.
      Improvement of psychosocial support and information to patients could lead to a
      better acceptance of reduced follow-up. The MaCare trial combines a reduced
      follow-up strategy with additional psychosocial support. Less frequent follow-up
      can reduce the burden on medical specialists and costs. The educational group
      programme can improve QoL of patients, but also less frequent follow-up can
      improve QoL by reducing the anxiety experienced for each follow-up visit. Results
      of the trial will provide knowledge on both costs and psychosocial aspects
      regarding follow-up and are expected in 2009.

PMID- 17199888
TI  - Internalization of novel non-viral vector TAT-streptavidin into human cells.
AB  - BACKGROUND: The cell-penetrating peptide derived from the Human immunodeficiency
      virus-1 transactivator protein Tat possesses the capacity to promote the
      effective uptake of various cargo molecules across the plasma membrane in vitro
      and in vivo. The objective of this study was to characterize the uptake and
      delivery mechanisms of a novel streptavidin fusion construct, TAT47-57
      streptavidin (TAT-SA, 60 kD). SA represents a potentially useful TAT-fusion
      partner due to its ability to perform as a versatile intracellular delivery
      vector for a wide array of biotinylated molecules or cargoes. RESULTS: By
      confocal and immunoelectron microscopy the majority of internalized TAT-SA was
      shown to accumulate in perinuclear vesicles in both cancer and non-cancer cell
      lines. The uptake studies in living cells with various fluorescent endocytic
      markers and inhibiting agents suggested that TAT-SA is internalized into cells
      efficiently, using both clathrin-mediated endocytosis and lipid-raft-mediated
      macropinocytosis. When endosomal release of TAT-SA was enhanced through the
      incorporation of a biotinylated, pH-responsive polymer poly(propylacrylic acid)
      (PPAA), nuclear localization of TAT-SA and TAT-SA bound to biotin was markedly
      improved. Additionally, no significant cytotoxicity was detected in the TAT-SA
      constructs. CONCLUSION: This study demonstrates that TAT-SA-PPAA is a potential
      non-viral vector to be utilized in protein therapeutics to deliver biotinylated
      molecules both into cytoplasm and nucleus of human cells.

PMID- 17199889
TI  - Evidence for a wide extra-astrocytic distribution of S100B in human brain.
AB  - BACKGROUND: S100B is considered an astrocytic in-situ marker and protein levels
      in cerebrospinal fluid (CSF) or serum are often used as biomarker for astrocytic
      damage or dysfunction. However, studies on S100B in the human brain are rare.
      Thus, the distribution of S100B was studied by immunohistochemistry in adult
      human brains to evaluate its cell-type specificity. RESULTS: Contrary to glial
      fibrillary acidic protein (GFAP), which selectively labels astrocytes and shows
      only faint ependymal immunopositivity, a less uniform staining pattern was seen
      in the case of S100B. Cells with astrocytic morphology were primarily stained by
      S100B in the human cortex, while only 20% (14-30%) or 14% (7-35%) of all
      immunopositive cells showed oligodendrocytic morphology in the dorsolateral
      prefrontal and temporal cortices, respectively. In the white matter, however,
      most immunostained cells resembled oligodendrocytes [frontal: 75% (57-85%);
      temporal: 73% (59-87%); parietal: 79% (62-89%); corpus callosum: 93% (86-97%)].
      S100B was also found in ependymal cells, the choroid plexus epithelium, vascular
      endothelial cells, lymphocytes, and several neurones. Anti-myelin basic protein
      (MBP) immunolabelling showed an association of S100B with myelinated fibres,
      whereas GFAP double staining revealed a distinct subpopulation of cells with
      astrocytic morphology, which solely expressed S100B but not GFAP. Some of these
      cells showed co-localization of S100B and A2B5 and may be characterized as O2A
      glial progenitor cells. However, S100B was not detected in microglial cells, as
      revealed by double-immunolabelling with HLA-DR. CONCLUSION: S100B is localized in
      many neural cell-types and is less astrocyte-specific than GFAP. These are
      important results in order to avoid misinterpretation in the identification of
      normal and pathological cell types in situ and in clinical studies since S100B is
      continuously used as an astrocytic marker in animal models and various human
      diseases.

PMID- 17199890
TI  - In vivo myograph measurement of muscle contraction at optimal length.
AB  - BACKGROUND: Current devices for measuring muscle contraction in vivo have limited
      accuracy in establishing and re-establishing the optimum muscle length. They are
      variable in the reproducibility to determine the muscle contraction at this
      length, and often do not maintain precise conditions during the examination.
      Consequently, for clinical testing only semi-quantitative methods have been used.
      METHODS: We present a newly developed myograph, an accurate measuring device for
      muscle contraction, consisting of three elements. Firstly, an element for
      adjusting the axle of the device and the physiological axis of muscle
      contraction; secondly, an element to accurately position and reposition the
      extremity of the muscle; and thirdly, an element for the progressive pre
      stretching and isometric locking of the target muscle. Thus it is possible to
      examine individual in vivo muscles in every pre-stretched, specified position, to
      maintain constant muscle-length conditions, and to accurately re-establish the
      conditions of the measurement process at later sessions. RESULTS: In a sequence
      of experiments the force of contraction of the muscle at differing stretching
      lengths were recorded and the forces determined. The optimum muscle length for
      maximal force of contraction was established. In a following sequence of
      experiments with smaller graduations around this optimal stretching length an
      increasingly accurate optimum muscle length for maximal force of contraction was
      determined. This optimum length was also accurately re-established at later
      sessions. CONCLUSION: We have introduced a new technical solution for valid,
      reproducible in vivo force measurements on every possible point of the stretching
      curve. Thus it should be possible to study the muscle contraction in vivo to the
      same level of accuracy as is achieved in tests with in vitro organ preparations.

PMID- 17199891
TI  - Effects of backpacking holidays in Australia on alcohol, tobacco and drug use of
      UK residents.
AB  - BACKGROUND: Whilst alcohol and drug use among young people is known to escalate
      during short holidays and working breaks in international nightlife resorts,
      little empirical data are available on the impact of longer backpacking holidays
      on substance use. Here we examine changes in alcohol, tobacco and drug use when
      UK residents go backpacking in Australia. METHODS: Matched information on alcohol
      and drug use in Australia and the UK was collected through a cross sectional
      cohort study of 1008 UK nationals aged 18-35 years, holidaying in Sydney or
      Cairns, Australia, during 2005. RESULTS: The use of alcohol and other drugs by UK
      backpackers visiting Australia was common with use of illicit drugs being
      substantially higher than in peers of the same age in their home country.
      Individuals showed a significant increase in frequency of alcohol consumption in
      Australia compared to their behaviour in the UK with the proportion drinking five
      or more times per week rising from 20.7% (UK) to 40.3% (Australia). Relatively
      few individuals were recruited into drug use in Australia (3.0%, cannabis; 2.7%
      ecstasy; 0.7%, methamphetamine). However, over half of the sample (55.0%) used at
      least one illicit drug when backpacking. Risk factors for illicit drug use while
      backpacking were being regular club goers, being male, Sydney based, travelling
      without a partner or spouse, having been in Australia more than four weeks,
      Australia being the only destination on their vacation and drinking or smoking
      five or more days a week. CONCLUSION: As countries actively seek to attract more
      international backpacker tourists, interventions must be developed that target
      this population's risk behaviours. Developing messages on drunkenness and other
      drug use specifically for backpackers could help minimise their health risks
      directly (e.g. adverse drug reactions) and indirectly (e.g. accidents and
      violence) as well as negative impacts on the host country.

PMID- 17199892
TI  - Comparing sequences without using alignments: application to HIV/SIV subtyping.
AB  - BACKGROUND: In general, the construction of trees is based on sequence
      alignments. This procedure, however, leads to loss of informationwhen parts of
      sequence alignments (for instance ambiguous regions) are deleted before tree
      building. To overcome this difficulty, one of us previously introduced a new and
      rapid algorithm that calculates dissimilarity matrices between sequences without
      preliminary alignment. RESULTS: In this paper, HIV (Human Immunodeficiency Virus)
      and SIV (Simian Immunodeficiency Virus) sequence data are used to evaluate this
      method. The program produces tree topologies that are identical to those obtained
      by a combination of standard methods detailed in the HIV Sequence Compendium.
      Manual alignment editing is not necessary at any stage. Furthermore, only one
      user-specified parameter is needed for constructing trees. CONCLUSION: The
      extensive tests on HIV/SIV subtyping showed that the virus classifications
      produced by our method are in good agreement with our best taxonomic knowledge,
      even in non-coding LTR (Long Terminal Repeat) regions that are not tractable by
      regular alignment methods due to frequent duplications/insertions/deletions. Our
      method, however, is not limited to the HIV/SIV subtyping. It provides an
      alternative tree construction without a time-consuming aligning procedure.

PMID- 17199894
TI  - Proteomic analysis of tyrosine phosphorylation during human liver
      transplantation.
AB  - BACKGROUND: Ischemia-reperfusion (I/R) causes a dramatic reprogramming of cell
      metabolism during liver transplantation and can be linked to an alteration of the
      phosphorylation level of several cellular proteins. Over the past two decades, it
      became clear that tyrosine phosphorylation plays a pivotal role in a variety of
      important signalling pathways and was linked to a wide spectrum of diseases.
      Functional profiling of the tyrosine phosphoproteome during liver transplantation
      is therefore of great biological significance and is likely to lead to the
      identification of novel targets for drug discovery and provide a basis for novel
      therapeutic strategies. RESULTS: Using liver biopsies collected during the early
      phases of organ procurement and transplantation, we aimed at characterizing the
      global patterns of tyrosine phosphorylation during hepatic I/R. A proteomic
      approach, based on the purification of tyrosine phosphorylated proteins followed
      by their identification using mass spectrometry, allowed us to identify Nck-1, a
      SH2/SH3 adaptor, as a potential regulator of I/R injury. Using immunoblot, cell
      fractionation and immunohistochemistry, we demonstrate that Nck-1
      phosphorylation, expression and localization were affected in liver tissue upon
      I/R. In addition, mass spectrometry identification of Nck-1 binding partners
      during the course of the transplantation also suggested a dynamic interaction
      between Nck-1 and actin during I/R. CONCLUSION: Taken together, our data suggest
      that Nck-1 may play a role in I/R-induced actin reorganization, which was
      previously reported to be detrimental for the hepatocytes of the transplanted
      graft. Nck-1 could therefore represent a target of choice for the design of new
      organ preservation strategies, which could consequently help to reduce post
      reperfusion liver damages and improve transplantation outcomes.

PMID- 17199893
TI  - Nasopharyngeal carcinoma: molecular biomarker discovery and progress.
AB  - Nasopharyngeal carcinoma (NPC) is a rare malignancy in most part of the world and
      it is one of the most confusing, commonly misdiagnosed and poorly understood
      diseases. The cancer is an Epstein-Barr virus-associated malignancy with a
      remarkable racial and geographical distribution. It is highly prevalent in
      southern Asia where the disease occurs at a prevalence about a 100-fold higher
      compared with other populations not at risk. The etiology of NPC is thought to be
      associated with a complex interaction of genetic, viral, environmental and
      dietary factors. Thanks to the advancements in genomics, proteomics and
      bioinformatics in recent decades, more understanding of the disease etiology,
      carcinogenesis and progression has been gained. Research into these components
      may unravel the pathways in NPC development and potentially decipher the
      molecular characteristics of the malignancy. In the era of molecular medicine,
      specific treatment to the potential target using technologies such as
      immunotherapy and RNAi becomes formulating from bench to bedside application and
      thus makes molecular biomarker discovery more meaningful for NPC management. In
      this article, the latest molecular biomarker discovery and progress in NPC is
      reviewed with respect to the diagnosis, monitoring, treatment and prognostication
      of the disease.

PMID- 17199895
TI  - Comparative genomic analysis of prion genes.
AB  - BACKGROUND: The homologues of human disease genes are expected to contribute to
      better understanding of physiological and pathogenic processes. We made use of
      the present availability of vertebrate genomic sequences, and we have conducted
      the most comprehensive comparative genomic analysis of the prion protein gene
      PRNP and its homologues, shadow of prion protein gene SPRN and doppel gene PRND,
      and prion testis-specific gene PRNT so far. RESULTS: While the SPRN and PRNP
      homologues are present in all vertebrates, PRND is known in tetrapods, and PRNT
      is present in primates. PRNT could be viewed as a TE-associated gene. Using human
      as the base sequence for genomic sequence comparisons (VISTA), we annotated
      numerous potential cis-elements. The conserved regions in SPRNs harbour the
      potential Sp1 sites in promoters (mammals, birds), C-rich intron splicing
      enhancers and PTB intron splicing silencers in introns (mammals, birds), and hsa
      miR-34a sites in 3'-UTRs (eutherians). We showed the conserved PRNP upstream
      regions, which may be potential enhancers or silencers (primates, dog). In the
      PRNP 3'-UTRs, there are conserved cytoplasmic polyadenylation element sites
      (mammals, birds). The PRND core promoters include highly conserved CCAAT, CArG
      and TATA boxes (mammals). We deduced 42 new protein primary structures, and
      performed the first phylogenetic analysis of all vertebrate prion genes. Using
      the protein alignment which included 122 sequences, we constructed the neighbour
      joining tree which showed four major clusters, including shadoos, shadoo2s and
      prion protein-likes (cluster 1), fish prion proteins (cluster 2), tetrapode prion
      proteins (cluster 3) and doppels (cluster 4). We showed that the entire prion
      protein conformationally plastic region is well conserved between eutherian prion
      proteins and shadoos (18-25% identity and 28-34% similarity), and there could be
      a potential structural compatibility between shadoos and the left-handed parallel
      beta-helical fold. CONCLUSION: It is likely that the conserved genomic elements
      identified in this analysis represent bona fide cis-elements. However, this idea
      needs to be confirmed by functional assays in transgenic systems.

PMID- 17199896
TI  - A novel three-dimensional system to study interactions between endothelial cells
      and neural cells of the developing central nervous system.
AB  - BACKGROUND: During angiogenesis in the developing central nervous system (CNS),
      endothelial cells (EC) detach from blood vessels growing on the brain surface,
      and migrate into the expanding brain parenchyma. Brain angiogenesis is regulated
      by growth factors and extracellular matrix (ECM) proteins secreted by cells of
      the developing CNS. In addition, recent evidence suggests that EC play an
      important role in establishing the neural stem cell (NSC) niche. Therefore, two
      way communication between EC and neural cells is of fundamental importance in the
      developing CNS. To study the interactions between brain EC and neural cells of
      the developing CNS, a novel three-dimensional (3-D) murine co-culture system was
      developed. Fluorescent-labelled brain EC were seeded onto neurospheres; floating
      cellular aggregates that contain NSC/neural precursor cells (NPC) and smaller
      numbers of differentiated cells. Using this system, brain EC attachment, survival
      and migration into neurospheres was evaluated and the role of integrins in
      mediating the early adhesive events addressed. RESULTS: Brain EC attached,
      survived and migrated deep into neurospheres over a 5-day period. Neurospheres
      express the ECM proteins fibronectin and laminin, and brain EC adhesion to
      neurospheres was inhibited by RGD peptides and antibodies specific for the beta1,
      but not the alpha6 integrin subunit. CONCLUSION: A novel 3-D co-culture system
      for analysing the interactions between EC and neural cells of the developing CNS
      is presented. This system could be used to investigate the reciprocal influence
      of EC and NSC/NPC; to examine how NSC/NPC influence cerebral angiogenesis, and
      conversely, to examine how EC regulate the maintenance and differentiation of
      NSC/NPC. Using this system it is demonstrated that EC attachment to neurospheres
      is mediated by the fibronectin receptor, alpha5beta1 integrin.

PMID- 17199897
TI  - Multiple upstream modules regulate zebrafish myf5 expression.
AB  - BACKGROUND: Myf5 is one member of the basic helix-loop-helix family of
      transcription factors, and it functions as a myogenic factor that is important
      for the specification and differentiation of muscle cells. The expression of myf5
      is somite- and stage-dependent during embryogenesis through a delicate
      regulation. However, this complex regulatory mechanism of myf5 is not clearly
      understood. RESULTS: We isolated a 156-kb bacterial artificial chromosome clone
      that includes an upstream 80-kb region and a downstream 70-kb region of zebrafish
      myf5 and generated a transgenic line carrying this 156-kb segment fused to a
      green fluorescent protein (GFP) reporter gene. We find strong GFP expression in
      the most rostral somite and in the presomitic mesoderm during segmentation
      stages, similar to endogenous myf5 expression. Later, the GFP signals persist in
      caudal somites near the tail bud but are down-regulated in the older, rostral
      somites. During the pharyngula period, we detect GFP signals in pectoral fin
      buds, dorsal rostral myotomes, hypaxial myotomes, and inferior oblique and
      superior oblique muscles, a pattern that also corresponds well with endogenous
      myf5 transcripts. To characterize the specific upstream cis-elements that
      regulate this complex and dynamic expression pattern, we also generated several
      transgenic lines that harbor various lengths within the upstream 80-kb segment.
      We find that (1) the -80 kb/-9977 segment contains a fin and cranial muscle
      element and a notochord repressor; (2) the -9977/-6213 segment contains a strong
      repressive element that does not include the notochord-specific repressor; (3)
      the -6212/-2938 segment contains tissue-specific elements for bone and spinal
      cord; (4) the -2937/-291 segment contains an eye enhancer, and the -2937/-2457
      segment is required for notochord and myocyte expression; and (5) the -290/-1
      segment is responsible for basal transcription in somites and the presomitic
      mesoderm. CONCLUSION: We suggest that the cell lineage-specific expression of
      myf5 is delicately orchestrated by multiple modules within the distal upstream
      region. This study provides an insight to understand the molecular control of
      myf5 and myogenesis in the zebrafish.

PMID- 17199899
TI  - Radiological physics within the framework of PAHO technical cooperation programs.

PMID- 17199898
TI  - TPRpred: a tool for prediction of TPR-, PPR- and SEL1-like repeats from protein
      sequences.
AB  - BACKGROUND: Solenoid repeat proteins of the Tetratrico Peptide Repeat (TPR)
      family are involved as scaffolds in a broad range of protein-protein
      interactions. Several resources are available for the prediction of TPRs,
      however, they often fail to detect divergent repeat units. RESULTS: We have
      developed TPRpred, a profile-based method which uses a P-value-dependent score
      offset to include divergent repeat units and which exploits the tendency of
      repeats to occur in tandem. TPRpred detects not only TPR-like repeats, but also
      the related Pentatrico Peptide Repeats (PPRs) and SEL1-like repeats. The
      corresponding profiles were generated through iterative searches, by varying the
      threshold parameters for inclusion of repeat units into the profiles, and the
      best profiles were selected based on their performance on proteins of known
      structure. We benchmarked the performance of TPRpred in detecting TPR-containing
      proteins and in delineating the individual repeats therein, against currently
      available resources. CONCLUSION: TPRpred performs significantly better in
      detecting divergent repeats in TPR-containing proteins, and finds more individual
      repeats than the existing methods. The web server is available at
      http://tprpred.tuebingen.mpg.de, and the C++ and Perl sources of TPRpred along
      with the profiles can be downloaded from
      ftp://ftp.tuebingen.mpg.de/ebio/protevo/TPRpred/.

PMID- 17199901
TI  - The role of diagnostic and therapeutic radiology in the field of public health.

PMID- 17199903
TI  - History of the radiological health program of the Pan American Health
      Organization.

PMID- 17199904
TI  - The role of professional networks in radiology services.
AB  - Recent developments in public health policy have high-lighted the central role of
      the clinical work force in the success of policy implementation, and thus the
      need for effective human resource policies. Given the high level of
      professionalism in health services, a number of special issues arise, including
      the organizational structures that best support professional work. Experiences
      from global industries that rely on a highly expert work force show that
      hierarchical control structures need to be supplemented by a variety of networks.
      Networks are complex structures that are very different from normal hierarchies,
      and they need to be effectively understood. While they usually develop
      spontaneously, they are often not optimally structured, adequately supported, or
      effectively exploited by health service organizations. It is important to
      understand the nature of networks and how they can be promoted in order to ensure
      that clinicians are appropriately supported in providing and enhancing services.

PMID- 17199905
TI  - Accreditation of diagnostic imaging services in developing countries.
AB  - In recent decades, medical imaging has experienced a technological revolution.
      After conducting several surveys to assess the quality and safety of diagnostic
      imaging services in Latin America and the Caribbean, the Pan American Health
      Organization (PAHO) developed a basic accreditation program that can be
      implemented by the ministry of health of any developing country. Patterned after
      the American College of Radiology's accreditation program, the PAHO program
      relies on a national accreditation committee to establish and maintain
      accreditation standards. The process involves a peer review evaluation of: (1)
      imaging and processing equipment, (2) physician and technologist staff
      qualifications, (3) quality control and quality assurance programs, and (4) image
      quality and, where applicable, radiation dose. Public and private conventional
      radiography/fluoroscopy, mammography, and ultrasound services may request
      accreditation. The radiography/fluoroscopy accreditation program has three
      modules from which to choose: chest radiography, general radiography, and
      fluoroscopy. The national accreditation committee verifies compliance with the
      standards. On behalf of the ministry of health, the accreditation committee also
      issues a three-year accreditation certificate. As needed, the accreditation
      committee consults with foreign technical and clinical experts.

PMID- 17199906
TI  - [The quality of radiology services in five Latin American countries].
AB  - OBJECTIVE: To determine the correlation between certain quality indicators for
      imaging services and the accurate interpretation of radiological exams for four
      frequent complaints: breast lumps, gastrointestinal discomfort, back pain, and
      symptoms of tuberculosis. METHODS: Twenty-six radiology services in Argentina,
      Bolivia, Colombia, Cuba, and Mexico were assessed. The mammography and
      conventional radiographic/fluoroscopic equipment used in selected services were
      evaluated utilizing common protocols, data sheets, testing instruments, phantoms,
      and calibrated dosimetry systems. The studies were performed in medium-complexity
      facilities. Informed consent was obtained from all patients studied, and the
      confidentiality of results was guaranteed. The following parameters were
      documented: type of facility (public vs. private); population covered; patient
      workload; radiological and image-processing equipment and supplies; education and
      training of professional and technical staff; quality assurance and preventive
      maintenance programs, and adherence to radiation safety standards. The
      performance of x-ray units, image receptors and processors; darkroom and image
      viewing conditions; patient doses and image quality, were determined using
      standardized parameters in all cases. Independent panels of radiologists,
      recognized as experts by the local radiological society, assessed the quality of
      the clinical images obtained and performed a radiological interpretation for each
      patient using the same films and clinical history available to the institution's
      imaging physicians. The agreement between the panel of expert's reports and those
      of local radiologists was taken as an indicator of the radiological diagnostic
      accuracy. RESULTS: Analyses were carried out of 366 mammograms, 343 radiological
      procedures for gastrointestinal complaints, 319 X-rays of the spinal column, and
      157 chest radiographs. The agreement between the radiological interpretation of
      the panel of experts and of the local physician ranged from 70% to 100%, except
      in the case of spinal column films in Cuba (57.8%) and of mammograms in Mexico
      (33.3%), which the panel of experts found to be among those having the poorest
      quality. There was a significant positive correlation between the accuracy of the
      radiological interpretation and the quality of the radiological images. Image
      quality showed a positive correlation with the technicians' level of education
      and training. Studies performed in services that had automatic film processors
      and that complied with the indicators established for screen-film contact yielded
      better images and a higher proportion of studies with concordant results. More
      than 50% of the viewboxes did not satisfy the quality criteria for luminance and
      homogeneity. CONCLUSIONS: A good quality image is critical to achieving an
      accurate diagnosis. Emphasis should be placed on the continuing education of
      radiology technicians and on the acquisition and maintenance of adequate
      equipment and accessories, especially viewboxes, intensifying screens, and
      automatic film processors, given the impact they have on image quality.

PMID- 17199907
TI  - Screening mammography: a successful public health initiative.
AB  - This paper reviews the ability of screening mammography to reduce breast cancer
      death rates, and it discusses methods that maximize benefits and reduce false
      positive interpretations in a screening program. The review covers published
      results from screening mammography programs conducted in Europe and North
      America, along with quality assurance measures designed to ensure that similar or
      even better outcomes will be shared by other populations of screened women.
      Randomized trials in Europe and the United States of America have shown the
      benefit from screening women ages 40-70 years. Encouraged by the success of these
      trials, many Scandinavian countries now offer screening mammography to their
      populations as a public health service. These service screening programs have
      reduced breast cancer deaths as much as 63% among women who were screened. In the
      United States, where 61.5% of women age 40 and older report having had a
      mammogram in the preceding year, death rates from breast cancer have been falling
      despite an increasing incidence of the disease. The technical quality of
      mammography in the United States has improved as a result of advances in
      mammography equipment, including the film-screen systems. Also contributing to
      the improvement has been the implementation of federally mandated quality control
      testing at each mammography facility, as required by the Mammography Quality
      Standards Act (MQSA), which the Congress of the United States approved in 1992.
      Factors that result in increased detection of early-stage cancers include better
      technique, use of two mammographic views per breast, annual screening intervals,
      and improved interpretation. Mammography is one of the 10 major subject
      categories on the American Board of Radiology examinations. Furthermore, MQSA
      requires radiologists who practice mammography to obtain continuing medical
      education credits and to use standard interpretation assessments on every report.
      Manuals for technical quality control and breast imaging reporting, as well as
      education and self-assessment materials on interpretation, have been developed by
      the American College of Radiology. Even though mammography will not detect all
      breast cancers, it is still the best available screening test. The American
      Cancer Society recommends that annual screening mammography begin no later than
      age 40 years.

PMID- 17199908
TI  - [Positron emission tomography: a new modality in Brazilian nuclear medicine].
AB  - In nuclear medicine, radioactive substances are used to diagnose and treat
      disease. This medical specialty, that can provide information about the human
      body's physiologic and metabolic processes, has become a key diagnostic tool for
      the early detection of many different disorders, including various types of
      cancer. The present article describes the historical milestones in nuclear
      medicine; the basic physical principles underlying positron emission tomography
      (PET), which is an imaging method used to map the distribution of
      radiopharmaceuticals in the body for diagnostic and therapeutic purposes, and the
      current status of this modality in Brazil.

PMID- 17199909
TI  - [New technologies: needs and challenges in radiotherapy in Latin America].
AB  - The cumulative experience gathered over more than a century of practice of
      radiotherapy has demonstrated the latter's importance not only for the palliative
      treatment of a fraction of cancer cases, but mainly for the curative treatment of
      an even greater proportion of such cases. In light of the changes in technology,
      the ever-increasing access developing countries to such technology, and its
      current coverage in Latin America, any efforts in this area should be aimed at
      improving the quality of the radiotherapy services and centers that are already
      in place. This involves developing their technological assets to the fullest,
      expanding their services, and complying with the minimum quality requirements
      established for second-level facilities. Each center should be equipped to carry
      out all stages of the radiotherapy process, from simulation through treatment
      verification and patient follow-up, with a high level of quality (level 2). To
      achieve this, it should possess the necessary technology and properly-trained
      staff that are required for the purpose. Collaborative efforts in the Region
      should also prioritize helping countries implement national treatment standards
      for all stages of the radiotherapy process and promoting the implementation of
      validated quality assurance programs.

PMID- 17199910
TI  - Normal tissue complications after radiation therapy.
AB  - This paper describes the biological mechanisms of normal tissue reactions after
      radiation therapy, with reference to conventional treatments, new treatments, and
      treatments in developing countries. It also describes biological reasons for the
      latency period before tissue complications arise, the relationship of dose to
      incidence, the effect of increasing the size of the irradiated volume, early and
      late tissue reactions, effects of changes in dose fractionation and dose rate,
      and combined chemotherapy and radiotherapy responses. Examples are given of
      increases in knowledge of clinical radiobiology from trials of new protocols.
      Potential modification to treatments include the use of biological response
      modifiers. The introduction of "response prediction" modifications to treatments
      might also be available in the near future. Finally, the paper points out that in
      some radiotherapy centers, the biologically-effective doses prescribed for
      combined brachytherapy and teletherapy treatment of cervix cancer are lower than
      those prescribed in other centers. This issue needs to be addressed further. The
      wealth of preclinical and clinical data has led to a much greater understanding
      of the biological basis to radiotherapy. This understanding has underpinned a
      variety of new approaches in radiotherapy, including both physical and biological
      strategies. There is also the important issue of treatment of a large number of
      cancers in developing countries, for which efficacious resource-sparing protocols
      are being continuously developed. A unified scoring system should be widely
      accepted as the new standard in reporting the adverse effects of radiation
      therapy. Likewise, late toxicity should be reported on an actuarial basis as a
      mandatory endpoint.

PMID- 17199911
TI  - Postal dose audits for radiotherapy centers in Latin America and the Caribbean:
      trends in 1969-2003.
AB  - Since 1969 the International Atomic Energy Agency and the World Health
      Organization (along with the Pan American Health Organization, working with
      countries in Latin America and the Caribbean) have operated postal dosimetry
      audits based on thermoluminescent dosimetry (TLD) for radiotherapy centers. The
      purpose of these audits is to provide an independent dosimetry check of radiation
      beams used to treat cancer patients. The success of radiotherapy treatment
      depends on accurate dosimetry. Over the period of 1969 through 2003 the
      calibration of approximately 5,200 photon beams in over 1,300 radiotherapy
      centers in 115 countries worldwide was checked. Of these audits, 36% were
      performed in Latin America and the Caribbean, with results improving greatly over
      the years. Unfortunately, in several instances large TLD deviations have
      confirmed clinical observations of inadequate dosimetry practices in hospitals in
      various parts of the world or even accidents in radiotherapy, such as the one
      that occurred in Costa Rica in 1996. Hospitals or centers that operate
      radiotherapy services without qualified medical physicists or without dosimetry
      equipment have poorer results than do hospitals or centers that are properly
      staffed and equipped. When centers have poor TLD results, a follow-up program can
      help them improve their dosimetry status. However, to achieve audit results that
      are comparable to those for centers in industrialized countries, additional
      strengthening of the radiotherapy infrastructure in Latin America and the
      Caribbean is needed.

PMID- 17199913
TI  - Counseling patients exposed to ionizing radiation during pregnancy.
AB  - Health physicists and knowledgeable clinicians have the responsibility to counsel
      women of reproductive age about the reproductive risks of ionizing radiation
      exposure before conception or during pregnancy. It is important to realize that
      lay individuals have many misconceptions about the reproductive risks of ionizing
      radiation. Many patients who have already had or will undergo some type of
      radiological test are apprehensive about the reproductive and developmental risks
      of diagnostic radiological procedures. Epidemiological studies and animal studies
      indicate that high exposures of ionizing radiation can cause miscarriage,
      congenital malformations, growth retardation, stillbirth, and cancer. With the
      exception of cancer, there are threshold exposures for those outcomes, with
      exposures below certain radiation doses not increasing the reproductive or
      developmental risks. The threshold exposure for birth defects at the most
      sensitive stage of development is 0.2 Gy, and the threshold for growth
      retardation and miscarriage is even higher. However, embryonic loss can occur
      from low exposures during the preimplantation and presomite stages of development
      ("the all or none period"). This is a stage when the embryo is more likely to die
      than survive malformed. The most sensitive period for the induction of mental
      retardation is from the 8th week to the 15th week of gestation. The threshold for
      deterministic effects increases after early organogenesis and also as the
      exposure is protracted, e.g., with radionuclides or multiple radiological
      procedures. Awareness that the threshold dose for developmental effects increases
      as the fetus develops complicates counseling because we do not have definitive
      data on threshold exposures at all stages of gestation. Ionizing radiation
      exposures prior to pregnancy represent a very low risk for the increased
      incidence of genetic disease in the offspring of the parents who have had
      radiation exposures to the ovary or testes. Counseling patients requires
      knowledge of embryology, genetics, radiation teratology, and the principles of
      teratology in order for the counselor to provide sympathetic, accurate, scholarly
      advice.

PMID- 17199912
TI  - Overexposure of radiation therapy patients in Panama: problem recognition and
      follow-up measures.
AB  - This report summarizes and analyzes the responses of various organizations that
      provided assistance to the National Oncology Institute (Instituto Oncologico
      Nacional, ION) of Panama following the overexposure of 28 radiation therapy
      patients at the ION in late 2000 and early 2001. The report also looks at the
      long-term measures that were adopted at the ION in response to the overexposure
      incident, as well as implications that the incident has for other cancer
      treatment centers worldwide. In March 2001, the director of the ION was notified
      of serious overreactions in patients undergoing radiation therapy for cancer
      treatment. Of the 478 patients treated for pelvic cancers between August 2000 and
      March 2001, 3 of them had died, possibly from an overdose of radiation. In
      response, the Government of Panama invited international experts to carry out a
      full investigation of the situation. Medical physicists from the Pan American
      Health Organization (PAHO) were among those invited. They ascertained that 56
      patients treated with partially blocked teletherapy fields for cancers of the
      uterine cervix, endometrium, prostate, or rectum, had had their treatment times
      calculated using a computerized treatment planning system. PAHO's medical
      physicists calculated the absorbed doses received by the patients and found that,
      of these 56 patients, only 11 had been treated with acceptable errors of +/-5%.
      The doses received by 28 of the 56 patients had errors ranging from +10 to +105%.
      These are the patients identified by ION physicists as overexposed. Twenty-three
      of the 28 overexposed patients had died by September 2005, with at least 18 of
      the deaths being from radiation effects, mostly rectal complications. The
      clinical, psychological, and legal consequences of the overexposures crippled
      cancer treatments in Panama and prompted PAHO to assess radiation oncology
      practices in the countries of Latin American and the Caribbean. ION clinicians
      evaluated the outcome of 125 non-overexposed patients who had been treated in the
      same time period and for the same cancer sites as the overexposed patients. The
      clinicians uncovered a larger recurrence of cervical cancers than expected. The
      finding prompted PAHO to launch an initiative for the accreditation of radiation
      oncology centers in Latin America and the Caribbean, working in collaboration
      with professional societies for radiation oncologists, medical physicists, and
      radiotherapy technologists. The Latin American Association for Radiation Oncology
      (Asociacion Latinoamericana de Terapia Radiante Oncologica) has established an
      accreditation commission. Accreditation will require that centers implement a
      comprehensive radiation oncology quality assurance program that follows
      international guidelines. Statistical data on patient outcomes will be collected
      in order to document needs in radiotherapy centers in Latin America and the
      Caribbean and to define future strategies for cancer treatment.

PMID- 17199914
TI  - [Norms and standards for radiofrequency electromagnetic fields in Latin America:
      guidelines for exposure limits and measurement protocols].
AB  - New technologies that use electromagnetic fields (EMF) have proved greatly
      beneficial to humankind. EMF are used in a variety of ways in the transmission of
      electrical energy and in telecommunications, industry, and medicine. However,
      some studies have shown that EMF could be detrimental to one's health, having
      found an association between exposure to EMF on the one hand, and the incidence
      of some types of cancer as well as behavioral changes on the other. Although so
      far there is no concrete proof that exposure to low-intensity EMF is hazardous,
      researchers continue to study the issue in an attempt to reach a consensus
      opinion and to establish safety standards. While developing and establishing such
      norms and standards have traditionally been the responsibility of international
      specialized agencies, national health authorities should take an active part in
      this process. Currently the Pan American Health Organization is promoting
      scientific research, often in the form of epidemiologic studies, in order to
      propose uniform norms and standards. Some Latin American countries, including
      Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Peru, and
      Venezuela, have already enacted incomplete or partial legislation based on
      recommended international standards. This article describes the norms established
      in Latin America and the particular approach taken by each country.

PMID- 17199915
TI  - [Present and future of studies on endometriosis (part two)].

PMID- 17199916
TI  - [Summary of the second national conference on endometriosis].

PMID- 17199917
TI  - [Effect of triptorelin and an extended-interval dosing regimen in the treatment
      of patients with endometriosis and adenomyoma].
AB  - OBJECTIVE: To study the role of triptorelin in the treatment of patients with
      endometriosis, adenomyoma and fibromyoma and the effect of an extended-interval
      dosing regimen. METHODS: Seventy patients suffering from endometriosis,
      adenomyoma and fibromyoma were divided into two groups: extended-interval dosing
      (group E) and conventional dosing (group C). There were treated with injection of
      triptorelin 3.75 mg intramuscularly either every 6 weeks of totally four dose
      regimen (group E) or every 4 weeks of six dose regimen (group C). Comparison was
      made in improvement of symptoms, size of uterus and volume of tumor, as well as
      in serum levels of 17beta-estradiol, luteinizing hormone, and follicle
      stimulating hormone. RESULTS: In each group, symptoms and tumor growth
      significantly improved after treatment (P < 0.05). For the patients of both
      groups E and C, the levels of gonadotropins and gonadal steroids were obviously
      reduced throughout the treatment period and up to 8 - 10 weeks after the
      injection of the last dose (P < 0.05). The hormonal profile of group E was
      similar to group C (P > 0.05). CONCLUSIONS: Gonadotropin-releasing hormone
      agonist is efficacious in the treatment of endometriosis and adenomyoma through
      reducing the serum levels of follicle-stimulating hormone, luteinizing hormone
      and 17beta-estradiol. The curative effect is satisfactory in most patients
      receiving an extended interval dosing regimen. To reduce the cost of treatment,
      the extended-interval dosing regimen of triptorelin should be adopted in well
      equipped hospitals.

PMID- 17199918
TI  - [Intermediate and long term clinical effects of uterine arterial embolization in
      treatment of adenomyosis].
AB  - OBJECTIVE: To assess the intermediate and long term clinical effectiveness of
      uterine arterial embolization (UAE) in treatment of adenomyosis. METHODS: The
      standard UAE was performed in 189 patients with adenomyosis in our hospital from
      Jun 1999 to Jun 2004. The fresh gelfoam particles or polyvinyl alcohol particles
      (PVA) or sodium alginate microspheres for vascular embolization (KMG) mixed with
      antibiotics were used to embolize the arteries. The degree of dysmenorrhea and
      amount of menorrhea after the operation were investigated. RESULTS: (1) The
      number of the cases completely followed up was 168, with a ratio of 88.9%, and a
      follow-up time of (50 +/- 15) months. (2) The symptom of dysmenorrhea: in all 168
      patients, 159 had dysmenorrhea before the operation. Clinical effectiveness was
      observed in 82.4% (131/159) of patients after the operation, but in 17.6%
      (28/159) of patients there was no clinical effectiveness, and in 5.0% (8/159) of
      patients the dysmenorrhea recurred after the operation. (3) The clinical
      effectiveness between the patients with adenomyosis with and without myoma or
      between the patients with local and diffuse adenomyosis had no significant
      difference (P > 0.05). (4) The amount of menorrhea: in the 93 patients with
      hypermenorrhea, the amount of menorrhea returned to normal in 83.9% (78/93),
      oligomenorrhea occurred in 10.8% (10/93), the menorrhea of 2 patients was rare,
      transient amenorrhea occurred in one case, and the amount of menorrhea did not
      change in two patients. Among the 74 patients with normal menorrhea, the
      menorrhea amount did not change in 77.0% (57/74), oligomenorrhea occurred in
      20.3% (15/74), uterine amenorrhea occurred in two patients. The menorrhea amount
      of one patient with oligomenorrhea returned to normal after the UAE therapy. (5)
      Nine patients accepted hysterectomy due to reoccurrence of dysmenorrhea or
      ineffectiveness or hypermenorrhea. CONCLUSION: UAE has a good intermediate and
      long term effectiveness in treatment of adenomyosis.

PMID- 17199919
TI  - [Effects of levonorgestrel-releasing intrauterine system on pain and recurrence
      associated with endometriosis and adenomyosis].
AB  - OBJECTIVE: To observe the effects of levonorgestrel-releasing intrauterine system
      (LNG-IUS) in treatment of pain associated with endometriosis (EM) and adenomyosis
      (AM), and in prevention of disease recurrence. METHODS: Thirty-three cases of
      moderate to severe EM or AM patients received insertion of LNG-IUS immediately
      after conservative operation, or after recurrence of simple pain, and were self
      controlled respectively before and after insertion of LNG-IUS. The visual
      analogue scale (VAS) was compared, and the change of the lesion and the uterine
      size, as well as the serum steroid and CA(125) were observed. The side-effects,
      such as bleeding pattern were recorded. The bleeding period was compared between
      the cases injected with or without gonadotropin-releasing hormone agonist (GnRHa)
      before insertion of LNG-IUS. RESULTS: Baseline and follow-up VASs of EM were 8.09
      +/- 0.21 and 1.64 +/- 1.12 (P = 0.042), of AM were 8.41 +/- 1.59 and 3.99 +/-
      3.87 (P = 0.068), respectively. During nearly 2 years' follow-up, moderate
      dysmenorrhea recurred in only 1 case who was hyper-estrogenism at that time.
      Generally, irregular bleeding and spotting period were longer in this LNG-IUS
      treated group than those reported in literatures in which LNG-IUS was used for
      contraception. Persistent prolonged spotting was seen in most of the patients
      during 1 year follow-up. Average bleeding days in one month during the first 6
      months after insertion of LNG-IUS were both around 18 days, whether using GnRHa
      or not. CONCLUSIONS: LNG-IUS greatly reduces pain associated with EM and AM, and
      delays disease recurrence. Irregular bleeding and spotting is the main side
      effects. Administration of GnRHa in advance does not improve the bleeding
      symptoms.

PMID- 17199920
TI  - [Analysis of relative factors influencing recurrence of endometriosis after
      operation treatment].
AB  - OBJECTIVE: To explore the relative factors influencing the recurrence of
      endometriosis. METHODS: Three hundred and fifty-six patients of endometriosis
      were treated with surgery and then followed up for 3 years. Seventy-five
      recurrent cases among them were analyzed retrospectively. RESULTS: The recurrent
      rate was different in the <or= 24 year age group (chi(2) = 11.212, P < 0.05),
      while there was no difference in the other age groups. According to pathological
      type, the recurrent rate of mixed pattern (29.2%) was significantly higher than
      that of the simple chocolate cyst (17.5%; chi(2) = 4.622, P < 0.05). The higher
      the clinical stage of the endometriosis, the higher the recurrent rate (P <
      0.05). The recurrent rate of endometriosis in the third stage was different
      between laparoscopy and laparotomy (31.3% vs 11.3%; chi(2) = 7.971, P < 0.01).
      Mifepristone could prolong the interval of recurrence after operation [(13 +/- 4)
      vs (7 +/- 3) months; t = 4.575, P < 0.01]. CONCLUSIONS: Individualized
      therapeutic regimen should be made in treatment of endometriosis according to
      age, pathological type, and clinical stage. The recurrent rate could be reduced
      and the interval of recurrence could be prolonged using ovarian function
      inhibiting drugs for a short time post-operation.

PMID- 17199922
TI  - [Expression and significance of metallothionein in the placenta of women with low
      level lead exposure during pregnancy].
AB  - OBJECTIVE: To investigate the significance of metallothionein (MT) expression in
      the placenta of women exposed to low level lead during pregnancy. METHODS: Sixty
      seven pregnant women with blood lead level ranging from 1.5 micromol/L to 4.8
      micromol/L were randomly selected from the Department of Obstetrics of Qingdao
      Municipal Hospital between Mar 2005 and Mar 2006. Among them, 35 were with blood
      lead level less than 2.9 micromol/L (group A) and 32 more than 2.9 micromol/L
      (group B). Immunohistochemical streptavidin-peroxidase-biotin methods were used
      to observe the expression of MT in the placental tissue. RESULTS: (1) Among the
      67 pregnant women, the highest level of blood lead was 4.7 micromol/L, and the
      lowest level was 1.6 micromol/L. The blood lead level of groups A and B was (1.7
      +/- 0.3) micromol/L, and (3.1 +/- 0.4) micromol/L, with a significant difference
      between them (P < 0.05). (2) The positive expression of MT was mainly cytoplastic
      in the cytotrophoblast, decidual cell and small vascular endothelial cells. The
      positive cell staining was diffuse or scattered. (3) The positive staining of MT
      was 91% (29/32) and 74% (26/35) in the placental tissue of groups A and B,
      respectively, with a significant difference between them (P < 0.05). (4) The
      blood lead level of pregnant women was correlated with the expression of MT of
      placenta. CONCLUSIONS: Lead can induce the expression of MT in the placental
      tissue in a dose-dependent manner. MT is mainly located in the cytotrophoblast,
      decidual cell and small vascular endothelial cells of the placenta. MT expression
      in the placenta is important to the structural integrity and function of the
      placenta.

PMID- 17199921
TI  - [Screening for G1528C mutation in mitochondrial trifunctional protein gene in
      pregnant women with severe preeclampsia and new born infant].
AB  - OBJECTIVE: Severe preeclampsia, and hemolysis, elevated liver enzymes, and low
      platelet syndrome (HELLP) are serious complications of pregnancy, and evidence
      suggests a genetic basis for these conditions. A G1528C mutation in the alpha
      subunit of the mitochondrial trifunctional protein (MTP) gene has been identified
      in association with these conditions. The aim of this study is to explore the
      carrier rate of the G1528C mutation in the MTP gene in pregnant women with severe
      preeclampsia, HELLP syndrome and in their newborns, as well as in a normal
      pregnant population, so as to determine its association with maternal liver
      disease among women in Beijing. METHODS: A multicenter, prospective, case control
      study was carried out. Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) was used to screen the G1528C mutations in the MTP gene.
      One hundred and forty cord blood samples from cases with severe preeclampsia (n =
      130) and HELLP syndrome (n = 10) were collected. Ninety maternal peripheral blood
      samples among them (84 from severe preeclampsia and 6 from HELLP syndrome) were
      also collected for screening the common disease-causing mutation in Caucasians.
      Five hundred and sixty cord blood samples and 90 maternal peripheral blood
      samples obtained from normal pregnant women served as controls. RESULTS: The
      G1528C mutations in the MTP gene were not found in samples from women with severe
      preeclampsia and their newborns, from women with HELLP syndrome and their new
      borns, as well as in samples from the normal pregnant women and their new borns.
      CONCLUSIONS: The common disease-causing mutation of G1528C in MTP gene in
      Caucasians is probably not a common mutation in Chinese Han people in Beijing.
      Further study is needed to expand the sample size among HELLP syndrome and
      maternal liver diseases in Chinese population.

PMID- 17199923
TI  - [Correlation of adipocytokines and insulin resistance in normal pregnancy].
AB  - OBJECTIVE: To explore the dynamic changes of adipocytokines and its correlation
      with insulin resistance during different stages of normal pregnancy. METHODS:
      Sixty-seven healthy pregnant women (18 first, 19 second and 30 third trimester)
      as experimental groups and 46 healthy age-matched non-pregnant women as a control
      group were investigated in a case-control cross-sectional study. Serum soluble
      tumor necrosis factor receptor (sTNFR) was determined by enzyme linked
      immunoadsorbent assay (ELISA). Maternal serum leptin and adiponectin were
      detected by radial immunodiffusion. TNF-alphaR in placenta and fat tissue was
      examined by streptavidin/peroxidase. RESULTS: The sTNFR-I level was higher in
      pregnant women than that in the control group (729 +/- 167) ng/L, being
      significantly higher in second (1003 +/- 241) ng/L and third trimesters (1278 +/-
      306) ng/L (P < 0.001). sTNFR-II level of first, second and third trimester groups
      (1383 +/- 305) ng/L, (1772 +/- 293) ng/L, (1933 +/- 498) ng/L was higher than
      that in the control group (1002 +/- 221) ng/L (P < 0.001) and was increased with
      the progress of gestation. Leptin level in late trimester (89 +/- 57) microg/L
      was significantly higher than that in control group (61 +/- 37) microg/L (P <
      0.05). Adiponectin level in second (9 +/- 5) mg/L and third trimesters (10 +/- 4)
      mg/L was significantly lower than that in control group (14 +/- 7) mg/L (P <
      0.05). The sTNFR-I and sTNFR-II were expressed in placenta and fat tissue.
      CONCLUSION: The dynamic changes of adipocytokines contribute to occurrence of
      insulin resistance.

PMID- 17199924
TI  - [Exploration of the classification of polycystic ovarian syndrome].
AB  - OBJECTIVE: To investigate the clinical presentation, hormonal profile and
      metabolic abnormalities in subgroups of women with PCOS and explore a reasonable
      classification for PCOS. METHODS: A cross-sectional study of 192 women with PCOS
      (14 - 38 years of age) was performed. The patients were divided into 3 groups of
      A, B and C according to the revised 2003 consensus on diagnostic criteria and
      also divided into 2 groups according to body mass index (BMI): group A (n = 110),
      long term anovulation, clinical and biochemical evidence of high androgen level,
      ovary enlargement with its size larger than 10 ml or number of small follicles of
      2 - 9 mm >or= 12 under ultrasound with exclusion of other diseases caused by high
      androgen; group B (n = 46), long term anovulation, clinical and biochemical
      evidence of high androgen level; group C (n = 36), long term anovulation, ovary
      enlargement with its size larger than 10 ml or number of small follicles of 2 - 9
      mm >or= 12 under ultrasound with exclusion of other disease caused by high
      androgen; obesity PCOS group (OB-PCOS, n = 70), BMI >or= 25 (kg/m(2)); no obesity
      PCOS group (NOB-PCOS, n = 122), BMI < 25 (kg/m(2)). One hundred and four women
      with bilateral tubal block factor caused infertility served as control group.
      Anthropometric measurements, Ferriman Gallwey hirsutism scoring, presence of acne
      and acanthosis nigricans were noted. Hormonal profile was assessed by measuring
      follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone
      (FT), prolactin (PRL), sex hormone binding globulin (SHBG). The metabolic profile
      was investigated by measurements of oral glucose tolerance test (OGTT), serum
      lipid levels, including total cholesterol (Chol), triglycerides (TG), high
      density lipoprotein (HDL), and low-density lipoprotein (LDL). Hyperinsulinemia
      was estimated by measurement of fasting insulin (FINS) and insulin area under the
      curve (IAUC). The extent of insulin resistance (IR) and hyperandrogenism was
      estimated by homeostasis model assessment (HOMA) and free androgen index (FAI)
      respectively. RESULTS: (1) Clinical phenotypes: the presence of obesity was 36.4%
      (70/192), among which 80.0% (56/70) were central obesity. Higher rates of
      acanthosis nigricans were observed in OB-PCOS group (35.7%, 25/70) compared with
      NOB-PCOS group (7.4%, 9/122; P < 0.01). Waist to hip ratio (WHR) was lower in
      group C than those in groups A and B (P < 0.05). (2) Endocrinology: FAI level was
      higher in OB-PCOS group than in NOB-PCOS group (P < 0.01), whereas LH/FSH ratio
      was lower in OB-PCOS group compared with NOB-PCOS group (P < 0.01). FAI level was
      higher in groups A and B than in group C (P < 0.01). SHBG, LH/FSH ratio did not
      differ between groups A, B, and C. (3) Metabolism: the prevalence of IR was 43.2%
      (83/192). A higher prevalence was observed in group OB-PCOS (82.8%, 58/70)
      compared with group NOB-PCOS (20.5%, 25/122; P < 0.01). FINS, HOMA-IR, glucose
      area under the curve (GAUC), IAUC and TG were higher in group OB-PCOS than in
      group NOB-PCOS (P < 0.01), whereas HOMA-IR, lipid profile did not differ between
      groups A, B, and C. CONCLUSION: The classification according to the revised 2003
      consensus on diagnosis reflects the basic characteristics of PCOS; while the
      classification based on obesity shows the severity of hyperandrogenism and degree
      of IR, and thus has substantial significance for evaluation of metabolic
      complications.

PMID- 17199925
TI  - [Fluid-based thin-layer method for screening of squamous intraepithelial lesions
      in pregnant women].
AB  - OBJECTIVE: To investigate the clinical significance and safety of liquid-based
      cytology (thinprep cytologic test, TCT) in pregnant women and cytological
      characteristics of the smears during pregnancy. METHODS: TCT were performed in
      1951 pregnant women (group A), 3752 gynecological out-patients (group B) and 5069
      routine screening women (group C). The age of the women was ranged from 20 to 39
      years. The cytological preparations were analyzed using TCT method following the
      Bathesda system (TBS) standard. RESULTS: (1) The incidence of abnormal epithelial
      patterns in groups A, B and C was 23.58% (460/1951), 19.22% (721/3752) and 13.40%
      (679/5069) respectively (P < 0.01). (2) The incidence of infection in three
      groups was 19.02% (371/1951), 10.66% (400/3752) and 9.23% (468/5069) respectively
      (P < 0.05). (3) The incidence of cervical intraepithelial neoplasia (CIN) in
      three groups was 1.13%, 1.87% and 0.77% respectively. No significant difference
      was found between pregnant group (A) and non-pregnant group (B + C, P > 0.05).
      CONCLUSIONS: TCT smear screening is necessary, safe and acceptable for routine
      prenatal tests. There is no difference in the cervical squamous intraepithelial
      lesions between pregnant and non-pregnant women.

PMID- 17199926
TI  - [Management and prognosis in stage IV gestational trophoblastic neoplasia
      patients].
AB  - OBJECTIVE: To analyze the management and prognosis in stage IV gestational
      trophoblastic neoplasia (GTN) patients. METHODS: One thousand one hundred and
      thirty GTN patients were hospitalized and treated at Peking Union Medical College
      Hospital from year 1985 to 2004. Ninety-two of them were diagnosed as stage IV of
      GTN. Retrospective analyses were carried out on these patients in terms of
      management and prognosis. RESULTS: Of the 92 patients who had undergone
      treatment, complete remission (CR) was achieved in 33, partial remission in 37,
      and progress of the disease was seen in 22. Among all the CR patients, three had
      recurrence later. Thirty-three out of all the patients died during or after
      treatment. Among the 92 cases, 70 had one or two metastases, of whom 27 had CR,
      and 20 died. Of the 17 cases who had three metastases, 5 achieved CR, and 10
      died. Of the five cases with >or= 4 metastases, one had CR, and three died. The
      number of metastatic organs was correlated with prognosis (P = 0.034) and death
      (P = 0.018). CONCLUSIONS: Multi-drug and multi-route chemotherapy and (or)
      combined surgical intervention may improve the survival rate of the stage IV GTN
      patients. The management should be individualized for different patients with
      metastases. With the increase in the number of metastatic organs, the remission
      rate decreases.

PMID- 17199927
TI  - [Meta-analysis of uterine arterial embolization and myomectomy in treatment of
      uterine myoma].
AB  - OBJECTIVE: To evaluate the effectiveness and safety of uterine arterial
      embolization (UAE) in the management of symptomatic uterine myomas compared with
      myomectomy. METHODS: All clinical trials on UAE treating symptomatic uterine
      myomas indexed in PubMed and Chinese National Knowledge Infrastructure (CNKI)
      were reviewed using meta-analysis by Revman 4.1 software. The patients were
      classified into two groups, i.e., UAE trial group and control group. Intervention
      method in control group was surgery of uterine myomectomy. There were no
      differences between two groups in age, general physical status, and manifestation
      of uterine myoma. RESULTS: Six hundred and eighty patients with symptomatic
      uterine myoma in eight trials were included into this study according to
      selection criteria of Cochrane collaboration. Meta-analysis indicated that weight
      of every trial contributing to the study was related to its number of patients in
      direct ratio, but not related to quality scale of the trial. There were no
      statistical differences between these trials in evaluation criteria (P > 0.05).
      Relative risk (RR) between UAE patients and control group was 0.95, and 95% CI
      was 0.92 - 0.99. The success rate (92.3%) of UAE group was 95% of control group
      (96.7%), with a significant difference between them (P < 0.05). CONCLUSIONS:
      Surgical procedures to treat uterine myomas have more effective outcomes than
      UAE. Patients who select UAE procedure may have 95% opportunity to improve
      clinical symptoms and avoid some surgical risks, and also have a higher life
      quality in future, although this has to be testified by long term follow-up.

PMID- 17199928
TI  - [Genetic aberrations and human papillomavirus status in vulvar squamous cell
      carcinomas].
AB  - OBJECTIVE: To investigate chromosomal gains and losses in association with human
      papillomavirus status in the vulvar squamous cell carcinomas (VSCC). METHODS: We
      analyzed 21 VSCC with comparative genomic hybridization (CGH) and polymerase
      chain reaction. RESULTS: Each case had different degree of variances, including
      gains and losses of partial or whole chromosome. On average, each case had 4.9
      (102/21) abnormal regions; losses were more than gains, being respectively 2.6
      (54/21) and 2.3 (48/21). Main variations were gains on chromosomes 3q (43%,
      9/21), 8q (38%, 8/21), 12q (33%, 7/21) and 9p (19%, 4/21), and losses of 4p (52%,
      11/21), 3p (43%, 9/21) and 9p (10%, 2/21). Gains of 3q (73%) and 12q (64%) were
      significantly more common in human papillomavirus (HPV)-positive VSCC compared to
      HPV-negative VSCC (10%, 0; P < 0.01). Gains on chromosome 8q (70%) were more
      commonly seen in HPV-negative compared to HPV-positive VSCC (9%, P < 0.01).
      CONCLUSIONS: Chromosomal gains or losses are detected by CGH in VSCC. The data
      indicate that gains of 3q and 12q coincide with HPV infection in VSCC.

PMID- 17199936
TI  - HIV/AIDS research in China: arising up from skyline.

PMID- 17199929
TI  - [Contraceptive efficacy of bioadhesive benzalkonium chloride gel in comparison
      with nonoxynol-9 gel].
AB  - OBJECTIVE: To compare the contraceptive efficacy of a new spermicide, bioadhesive
      benzalkonium chloride (BZK) gel, with the traditional nonoxynol (NP-9) gel.
      METHODS: A total of 240 child-bearing age women volunteers were randomly divided
      into two groups: 120 using the BZK gel for contraception, and the other 120 using
      the NP-9 gel. Using life table method and log-rank test, we compared the
      pregnancy rates and discontinuation rates after follow-up for 6 months in two
      groups. RESULTS: No abnormal findings of cervical smears were detected before and
      after this clinical trial in all 240 women. The follow-up rates at 6 months were
      100.0% and 99.2% in the BZK group and the NP-9 group, respectively. The 6-month
      gross cumulative pregnancy rates of typical use were 1.72 and 0.91 per 100 women
      (P > 0.05), respectively. If we excluded the 2 pregnant women (1 in each group),
      who did not correctly or consistently use the spermicides for every intercourse,
      the cumulative pregnancy rates at 6 months in perfect use would be 0.87 and 0 per
      100 women (P > 0.05). And the gross cumulative discontinuation rates due to
      allergy or other adverse reactions at 6 months in typical use were 0 and 2.68 per
      100 women (P > 0.05), respectively. CONCLUSION: The contraceptive efficacy of
      bioadhesive BZK gel is the same as that of the NP-9 gel, and it is more
      acceptable in clinical use.

PMID- 17199937
TI  - Epidemiology, clinical and laboratory characteristics of currently alive HIV-1
      infected former blood donors naive to antiretroviral therapy in Anhui Province,
      China.
AB  - BACKGROUND: Unregulated commercial blood/plasma collection among farmers occurred
      between 1992 and 1995 in central China and caused the second major epidemic of
      human immunodeficiency virus type 1 (HIV-1) infection in China. It is important
      to characterize HIV-1-infected former blood donors and to study characteristics
      associated with disease progression for future clinical intervention and vaccine
      development. METHODS: A cross-sectional study was performed on HIV-1-infected
      former blood donors (FBDs) and age-matched HIV-seronegative local residents.
      Demographic, epidemiologic, clinical and key laboratory data were collected from
      all study participants. Both unadjusted and adjusted multivariate linear
      regressions were employed to analyze the association of the decrease of CD4(+) T
      cell counts with other characteristics. RESULTS: Two hundred and ninety-four HIV
      1-infected FBDs and 59 age-matched HIV-seronegative local residents were enrolled
      in this study. The unregulated blood/plasma collection occurred more than a
      decade (10.8 - 12.8 years) ago, which caused the rapid spread of HIV-1 infection
      and the high prevalence of co-infection with hepatitis C virus (HCV, 89.5%);
      hepatitis B virus (HBV) co-infection was observed in only 11 HIV(+)participants
      (3.7%). Deterioration in both clinical manifestation and laboratory parameters
      and increase of viral loads were observed in parallel with the decrease of CD4(+)
      T-cell counts. The decrease of total lymphocyte counts (P < 0.001) and hemoglobin
      levels (P < 0.001) and the appearance of dermatosis (P = 0.03) were observed in
      parallel with the decrease of CD4(+) T-cell counts whereas viral loads (P <
      0.001) and CD8(+) T-cell counts (P = 0.01) were inversely associated with CD4(+)
      T-cell counts. CONCLUSIONS: Co-infection with HCV but not HBV is highly prevalent
      among HIV-1-infected FBDs. CD4(+) T-cell counts is a reliable indicator for
      disease progression among FBDs. Total lymphocyte counts, hemoglobin level and
      appearance of dermatosis were positively associated with CD8(+) T-cell counts and
      viral loads were inversely associated with the decreased CD4(+) T-cell counts.

PMID- 17199938
TI  - Characteristics of HIV-1-specific CD8 T-cell responses and their role in loss of
      viremia in children chronically infected with HIV-1 undergoing highly active
      antiretroviral therapy.
AB  - BACKGROUND: Few studies have examined the properties of human immunodeficiency
      virus type 1 (HIV-1) epitope-specific cytotoxic T lymphocyte (CTL) responses in
      children. To address this issue, we characterized epitope-specific CTL responses
      and analyzed the determinants that may affect CTL responses before and after
      highly active antiretroviral therapy (HAART) in children with HIV-1 infection.
      METHODS: A total of 22 HIV-1-infected children and 23 uninfected healthy children
      as control were enrolled in the study. Circulating CD4 T cells and HIV-1 RNA load
      in plasma were routinely measured. Peripheral HIV-1-specific CTL frequency and
      HIV-1 epitope-specific, interferon-gamma (IFN-gamma)-producing T lymphocytes were
      measured using tetramer staining and enzyme-linked immunospot (ELISPOT) assay,
      respectively. Circulating dendritic cell (DC) subsets were monitored with FACS
      analysis. RESULTS: More than 80% of the children with HIV-1 infection exhibited a
      positive HIV-1-epitope-specific CTL response at baseline, but HIV-specific CTLs
      and IFN-gamma-producing lymphocytes decreased in patients who responded to HAART
      in comparison with non-responders and HAART-naive children. The duration of virus
      suppression resulted from HAART was inversely correlated with CTL frequency.
      While in HAART-naive children, HIV-1-specific CTL frequency was positively
      correlated with myeloid DC (mDC) frequency, although the cause and effect
      relationship between the DCs and CTLs remains unknown. CONCLUSIONS: HIV-1-epitope
      specific CTL responses are dependent on antigenic stimulation. The impaired DC
      subsets in blood might result in a defect in DC-mediated T cell responses. These
      findings may provide insight into understanding the factors and related
      mechanisms that influence the outcome of HIV-1 carriers to HAART or future
      antiviral therapies.

PMID- 17199939
TI  - HIV-specific T cell immunity across the entire HIV genome in Chinese men who have
      sex with men.
AB  - BACKGROUND: Man who has sex with man (MSM) is one of the high risk groups for
      spreading HIV/AIDS. It was reported that the most prevalent human
      immunodeficiency virus type 1 (HIV-1) strain among MSM is subtype B; however, T
      cell immunity remains unknown across the HIV-1 B genome in this population.
      METHODS: Using Elispot assay with synthetic peptides spanning the sequence of HIV
      1 consensus B, HIV-1-specific cytotoxic T-cell lymphocyte responses were
      quantified among 3 treated and 19 untreated HIV-1 infected MSM from Beijing,
      China. Cross-sectional association between viral loads and cellular immune
      responses were analyzed. RESULTS: Peptide pools corresponding to each HIV-1
      protein were used for Env, Gag, Pol, Nef, Tat/Rev, Vpr/Vpu and Vif. The results
      showed that the magnitude of T cell responses in the 3 treated HIV(+) MSM group
      [median, 770 spot forming cells (SFCs) per 10(6) peripheral blood mononuclear
      cells (PBMCs)] might be significantly lower than that in the 19 untreated HIV(+)
      MSM group (median, 6175 SFCs per 10(6) PBMCs). Nef, Gag and Pol are the most
      frequently targeted HIV-1 antigens; and 16 subjects (73%) were identified with
      vigorous T cell immunity against each of these three proteins. The overall
      magnitude of T cell immunity closely related to its breadth (r = 0.72, P < 0.05)
      and was inversely but weakly associated with viral loads (r = -0.15). Further
      analysis showed that both Gag (r = -0.24) and Pol specific T cells (r = -0.12)
      contributed to this inverse association whereas Nef specific T cells showed no
      association with viral loads. CONCLUSIONS: The magnitude of HIV-1 specific T
      cells is inversely but weakly associated with viral loads among MSM; HIV-specific
      T cell responses against conservative sequences (Gag and Pol) are the main
      contributors to this association among Chinese HIV(+) MSM. These findings have
      important implications for vaccine design.

PMID- 17199940
TI  - Activation and coreceptor expression of T lymphocytes induced by highly active
      antiretroviral therapy in Chinese HIV/AIDS patients.
AB  - BACKGROUND: At the end of 2005, 650,000 people lived with human immunodeficiency
      virus type-1 (HIV-1) in China, of whom 75 000 were AIDS patients. Many AIDS
      patients received highly active antiretroviral therapy (HAART) supported by the
      "China CARES" program but the immune responses of HAART were seldom reported.
      This study investigated the effect of HAART on the activation and coreceptor
      expression of T lymphocytes in Chinese HIV/AIDS patients and evaluated its effect
      on immune reconstitution. METHODS: Seventeen HIV/AIDS patients were enrolled and
      three-color-flow cytometry was used to detect the activation of HLA-DR CD38 and
      the coreceptor CCR5, CXCR4 expression on T lymphocytes in whole blood samples
      taken from the patients before and after 3- or 6-month HAART. RESULTS: The
      activation percents of CD4(+), CD8(+) T lymphocytes were significantly higher
      before therapy than the normal controls (HLA-DR/CD4: 40.47 +/- 18.85 vs 11.54 +/-
      4.10; CD38/CD4: 81.34 +/- 10.86 vs 53.34 +/- 11.44; HLA-DR/CD8: 63.94 +/- 12.71
      vs 25.67 +/- 9.18; CD38/CD8: 86.56 +/- 11.41 vs 58.84 +/- 6.16, all P < 0.01).
      After 6-month combined antiretroviral treatment, the activation of T lymphocytes
      in HIV/AIDS patients was significantly decreased (HLA-DR/CD4: 28.31 +/- 13.48;
      CD38/CD4: 69.88 +/- 12.64; HLA-DR/CD8: 46.56 +/- 18.64; CD38/CD8: 70.17 +/-
      14.54, all P < 0.01 compared with the pre-treatment values). Before the
      treatment, CCR5 expression on CD8(+) T lymphocytes was up-regulated while CXCR4
      expression on CD8(+) T lymphocytes downregulated in HIV/AIDS patients compared
      with the normal controls (CD8/CCR5: 70.91 +/- 10.03 vs 52.70 +/- 7.68; CD8/CXCR4:
      24.14 +/- 11.08 vs 50.05 +/- 11.68, all P < 0.01). After 6-month HAART, CCR5
      expression on CD8(+) T lymphocytes significantly decreased (56.35 +/- 12.96, P <
      0.01), while CXCR4 expression on CD8(+) T lymphocytes increased (36.95 +/- 9.96,
      P < 0.05) compared with the pre-treatment and the normal controls. A significant
      statistical relationship was observed between the expression of activation
      markers, CCR5 and the CD4(+) T lymphocyte counts after HAART (P < 0.05).
      CONCLUSIONS: Reduced activation of T lymphocytes and a normalization of
      coreceptor expression were observed in Chinese HIV/AIDS patients after HAART.
      Immunity can be restored in HIV/AIDS patients receiving HAART.

PMID- 17199941
TI  - Phenotypic resistance of resistant strains of HIV type-1 subtype B in China.
AB  - BACKGROUND: This study was aim to explore the characteristics of phenotypic
      resistance of resistant strains of HIV type-1 (HIV-1) subtype B and to compare
      the concordance between the phenotypic resistance and genotypic resistance.
      METHODS: The genotypic resistance assay for the HIV-1 clinical isolates was
      performed. One isolate without resistance mutation was chosen as a drug-sensitive
      reference strain and seven subtype B isolates with resistance mutations were
      phenotypically tested. Fifty percent inhibitory concentrations (IC50) between
      resistant and sensitive viruses were compared. The resistance extent was
      determined by the folds of the increased IC50. The concordance between the
      phenotypic resistance and genotypic resistance was also analyzed. RESULTS: IC50
      of resistant isolates were 0.0006 - 0.1300 micromol/L for zidovudine (AZT),
      0.0016 - 0.0390 micromol/L for lamivudine (3TC), 0.0104 - 0.4234 micromol/L for
      nevirapine (NVP), and 0.0163 - 0.1142 micromol/L for indinavir (IDV),
      respectively. Genotypic and phenotypic resistance assays indicated that the
      resistant strains were intermediately and highly resistant to nucleotide analog
      reverse transcriptase inhibitors and non-nucleotide analog reverse transcriptase
      inhibitors. The phenotypic assay was consistent with the genotypic assay. For
      measuring the potential resistance, the genotypic assay was more sensitive than
      the phenotypic. In evaluating the resistance to protease inhibitors, these two
      assays were discrepant. CONCLUSIONS: Both the phenotypic and genotypic assays
      indicate that the resistant viruses exist in HIV-infected patients in China who
      have received treatment. Phenotypic and genotypic assays have high concordance,
      and the genotypic assay could replace the phenotypic assay to predict the HIV-1
      resistance.

PMID- 17199943
TI  - CD69 expression on airway eosinophils and airway inflammation in a murine model
      of asthma.
AB  - BACKGROUND: Asthma is a chronic airway disease with inflammation characterized by
      physiological changes (airway hyper-responsiveness, AHR) and pathological changes
      (inflammatory cells infiltration and mucus production). Eosinophils play a key
      role in the allergic inflammation. But the causative relationship between
      eosinophils and airway inflammation is hard to prove. One of the reasons is lack
      of activation marker of murine eosinophils. We investigated the expression of
      CD69 on murine eosinophils in vitro, the relationship between the expression of
      CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on
      airway inflammation in asthmatic mice. METHODS: Eosinophils from peripheral blood
      of IL-5 transgenic mice (NJ.1638) were purified. Mice were divided into five
      groups: wild type mice sensitized and challenged with saline (WS group), wild
      type mice sensitized and challenged with ovalbumin (WO group), IL-5(-/-) mice
      sensitized and challenged with saline and transferred with purified eosinophils
      (ISE group), IL-5(-/-) mice sensitized and challenged with OVA and transferred
      with purified eosinophils (IOE group), IL-5(-/-) mice sensitized and challenged
      with OVA and transferred with purified eosinophils, pretreated with anti CD4
      monoclonal antibody (IOE+antiCD4mAb group). IL-5(-/-) mice were sensitized with
      OVA at day 0 and day 14, then challenged with OVA aerosol. On days 24, 25, 26 and
      27 purified eosinophils were transferred intratracheally to IL-5(-/-) mice. On
      day 28, blood and BALF were collected and CD69 expression on eosinophils measured
      by flowcytometry. RESULTS: Purified eosinophils did not express CD69. But
      eosinophils cultured with PMA + MA, IFN-gamma, IL-5 or GM-CSF expressed CD69
      strongly. Eosinophils from blood of WO, WS group did not express CD69 at all. The
      numbers of eosinophils in BALF of WO group, IOE group, ISE group and IOE +
      antiCD4mAb group were significantly higher than in mice of WS group which did not
      have eosinophils at all. CD69 expression on eosinophils in BALF of IOE and WO
      groups was strong. Eosinophils in BALF of ISE and IOE + antiCDmAb groups did not
      express CD69. The mucus production result was similar to CD69 expression. There
      were eosinophils infiltration in lung slides of all groups except WS group.
      CONCLUSION: Activation in airway of eosinophils could directly lead to airway
      inflammation.

PMID- 17199942
TI  - Evaluation of hyperbaric oxygen treatment of neuropsychiatric disorders following
      traumatic brain injury.
AB  - BACKGROUND: Improvement of clinical symptoms following hyperbaric oxygen (HBO)
      treatment of neuropsychiatric disorders arising from traumatic brain injury was
      proved by our previous study. This study was aim to obtain the evidence of other
      changes. METHODS: Three hundred and ten patients with neuropsychiatric disorders
      arising from traumatic brain injury were treated twice with hyperbaric oxygen.
      Cerebral single photon emissions computed tomography (SPECT) images and computed
      tomography scans (CT) before and after hyperbaric oxygen treatment, were
      compared. RESULTS: Before treatment, the proportion of abnormal cerebral changes
      detected by SPECT was 81.3% but only 15.2% by CT. After HBO treatment, 70.3% of
      SPECT scans showed no abnormalities and these patients were clinically improved.
      Treatment improved regional cerebral blood flow. CONCLUSION: SPECT was much more
      sensitive than CT in the diagnosis of neuropsychiatric disorders following
      hyperbaric oxygen treatment of neuropsychiatric disorders arising from traumatic
      brain injury.

PMID- 17199944
TI  - Effects of recombinant retroviral vector mediated human insulin like growth
      factor-1 gene transfection on skeletal muscle growth in rat.
AB  - BACKGROUND: This study transferred a recombinant gene encoding human insulin like
      growth factor-1 (hIGF-1) into modified primary skeletal myoblasts with a
      retroviral vector (pLgXSN) and determined whether the hIGF-1 promoted growth of
      skeletal muscle in rat. METHODS: hIGF-1cDNA was amplified in vitro from normal
      human liver cells by using RT-PCR and cloned into plasmid vector pLgXSN. The
      recombinant vector pLghIGF-1SN and control vector pLgGFPSN were transfected into
      packaging cell PT67 and G418 was used to select positive colony. Myoblasts were
      infected with a high titre viral supernatant and transduction efficiency was
      evaluated as GFP expression. The expression of hIGF-1 mRNA in myoblasts was
      investigated by immunocytochemistry and RT-PCR. MTT assays detected the growth of
      myoblasts in vitro. Myoblasts transduced with pLghIGF-1SN were injected into hind
      limb muscles of 10 - 12 week male SD rats. Formed tissues were harvested 4 weeks
      later. Myocyte diameter, mean weight of hind limb and body were measured to
      evaluate the skeletal muscle growth. RESULTS: Recombinant retroviral plasmid
      vector pLghIGF-1SN was constructed successfully. The titre of the packaged
      recombinant retrovirus was 1 x 10(6) cfu/ml. The transfection rate of PT67 cells
      reached 100% after G418 screening. hIGF-1 expression was positive in myoblast-IGF
      1. The proliferation rate of myoblast-IGF-1 in vitro was higher than GFP-myoblast
      or myoblast (P < 0.05). The mean weights of hind limb and body of rats injected
      myoblast-IGF-1 were higher than those of the rats injected with myoblast-GFP or
      myoblast (P < 0.05). Myocyte diameter had a significant increase in IGF-1 group
      compared to GFP group and myoblast group (P < 0.05). CONCLUSIONS: The
      transfection of the human IGF-1 gene mediated by a retroviral vector can promote
      the growth of skeletal muscle in rats. Genetically modified primary skeletal
      myoblasts provide a possibly effective approach to treat some skeletal muscle
      diseases.

PMID- 17199945
TI  - Overview of HIV drug resistance and its implications for China.

PMID- 17199947
TI  - Simultaneous analysis of tramadol, metoprolol and their metabolites in human
      plasma and urine by high performance liquid chromatography.

PMID- 17199946
TI  - Recent progress of pediatric cardiac surgery in China.

PMID- 17199948
TI  - Surgical treatment of posttraumatic foreign bodies in the heart or great vessels.
AB  - Posttraumatic foreign bodies in the heart or great vessels is rare, which may
      cause cardiac tamponade, bleeding, shock, infection, embolism, arrhythmia, valve
      dysfunction, etc. The foreign bodies can be removed by surgery or percutaneous
      intervention. In this report we reviewed our experience in managing posttraumatic
      foreign bodies in 13 patients at our institution from 1992 to 2002.

PMID- 17199950
TI  - Conference report: recent advances on thrombosis and haemostasis in Asian Pacific
      region: report of the Fourth Asian Pacific Congress on Thrombosis and
      Haemostasis.

PMID- 17199949
TI  - Primary tumors of the heart: the great masqueraders.

PMID- 17199951
TI  - Atrial fibrillation and rheumatic valvular heart disease: usefulness of very-low
      dose amiodarone.

PMID- 17199952
TI  - Long-term efficacy and safety of very-low-dose amiodarone treatment for the
      maintenance of sinus rhythm in patients with chronic atrial fibrillation after
      successful direct-current cardioversion.
AB  - BACKGROUND: Long-term maintenance of sinus rhythm after successful conversion of
      chronic atrial fibrillation (CAF), often ameliorates patients' symptoms, reduces
      the risk of ischemic stroke and improves cardiovascular hemodynamics. This
      prospective study aims to evaluate the long-term efficacy and safety of very low
      dose amiodarone (100 mg daily) for the maintenance of sinus rhythm after
      successful direct-current (DC) cardioversion in patients with CAF and rheumatic
      heart disease (RHD) post intervention. METHODS: This study was a randomized
      prospective trial. One day after successful DC cardioversion (remained normal
      sinus rhythm) in patients with CAF and RHD post intervention for more than six
      months and adequate anticoagulation, all were randomly administered either
      amiodarone 200 mg daily in group A or amiodarone 100 mg daily in group B.
      RESULTS: A total of 76 patients (40 men and 36 women) were examined from February
      1998 to December 1999. The mean age of the patients was (66 +/- 10) years, and
      the mean follow-up was (67 +/- 8) months (range 61 to 84 months). Actuarial rates
      of the maintenance of sinus rhythm were similar in the two groups after 5 years
      of follow-up. Four patients (11%) in group A but none in group B experienced
      significant adverse effects that necessitated withdrawal of amiodarone. No death
      occurred during the study period. CONCLUSION: A very low dose of amiodarone
      results in adequate long-term efficacy and is safe for maintaining sinus rhythm
      in patients with CAF and RHD post intervention after successful DC cardioversion.

PMID- 17199953
TI  - Radiofrequency catheter ablation in patients with symptomatic atrial
      flutter/tachycardia after orthotopic heart transplantation.
AB  - BACKGROUND: Atrial tachycardia or flutter is common in patients after orthotopic
      heart transplantation. Radiofrequency catheter ablation to treat this arrhythmia
      has not been well defined in this setting. This study was conducted to assess the
      incidence of various symptomatic atrial arrhythmias and the efficacy and safety
      of radiofrequency catheter ablation in these patients. METHODS:
      Electrophysiological study and catheter ablation were performed in patients with
      symptomatic tachyarrhythmia. One Halo catheter with 20 poles was positioned
      around the tricuspid annulus of the donor right atrium, or positioned around the
      surgical anastomosis when it is necessary. Three quadripolar electrode catheters
      were inserted via the right or left femoral vein and positioned in the recipient
      atrium, the bundle of His position, the coronary sinus. Programmed atrial
      stimulation and burst pacing were performed to prove electrical conduction
      between the recipient and the donor atria and to induce atrial arrhythmias.
      RESULTS: Out of 55 consecutive heart transplantation patients, 6 males [(58 +/-
      12) years] developed symptomatic tachycardias at a mean of (5 +/- 4) years after
      heart transplantation. Electrical propagation through the suture line between the
      recipient and the donor atrium was demonstrated during atrial flutter or during
      recipient atrium and donor atrium pacing in 2 patients. By mapping around the
      suture line, the earliest fragmented electrogram of donor atrium was assessed.
      This electrical connection was successfully ablated in the anterior lateral
      atrium in both patients. There was no electrical propagation through the suture
      line in the other 4 patients. Two had typical atrial flutter in the donor atrium
      which was successfully ablated by completing a linear ablation between the
      tricuspid annulus and the inferior vena cava. Two patients had atrial tachycardia
      which was ablated in the anterior septal and lateral donor atrium. There were no
      procedure-related complications. Patients were free of recurrent atrial
      tachyarrhythmias after a follow-up of (8 +/- 7) months. CONCLUSIONS: Four
      electrophysiological mechanisms have been found to contribute to the occurrence
      of symptomatic supraventricular arrhythmias following heart transplantation.
      Radiofrequency catheter ablation in patients with atrial flutter/tachycardia is
      feasible and safe after heart transplantation.

PMID- 17199954
TI  - Linear ablation of left atrium for the treatment of atrial fibrillation guided by
      double Lasso catheters and three dimensional electroanatomical mapping.
AB  - BACKGROUND: Linear ablation of left atrium (LA) guided by three dimensional (3-D)
      electroanatomical mapping (Carto) has been used in many centres worldwide for the
      treatment of atrial fibrillation (AF) instead of pure anatomical approaches.
      There were little data about linear ablation of LA guided by Carto and double
      Lasso catheters in China. We report the results of linear ablation of LA guided
      by both Carto and double Lasso catheters. METHODS: After the anatomical model of
      LA and all pulmonary veins (PVs) had been established, circumferential ablations
      of the left pulmonary vein antrum and the right pulmonary vein antrum were
      performed with 2 circumferential mapping catheters (Lasso) placed within the
      ipsilateral superior and inferior PVs. The endpoint of ablation was abolishment
      or dissociation of the pulmonary vein potentials (PVPs). Oral amiodarone or
      propafenone was taken for at least 3 months by patients with persistent AF,
      permanent AF or those whose PVPs had not been isolated completely. The recurrence
      of atrial tachyarrhythmias was observed 3 months after the procedure. RESULTS:
      There were 106 patients (mean age, 51.4 +/- 9.9 years). Seventy-eight patients
      had paroxysmal AF, 12 persistent AF and 16 permanent AF. Onset of atrial
      fibrillation occurred in 52 patients during ablation procedure. Thirty-two
      patients restored to sinus rhythm eventually after the procedure. Abolishment or
      dissociation of PVPs was accomplished during the procedure in 94 patients
      (88.7%). The duration of procedure and exposure to X-ray were (213 +/- 45)
      minutes and (32.5 +/- 12.8) minutes, respectively. Among the 87 patients followed
      up for over 3 months, 62 were free of atrial tachyarrhythmias (including 8
      patients who were still taking oral amiodarone). The success rate was 71.3% in
      the first procedure. Two patients had pericardial effusion treated by pericardial
      puncture and effusion drainage. No pulmonary vein stenosis, atrioesophageal
      fistula, stroke or procedural death occurred. CONCLUSIONS: Combination of double
      Lasso catheters with 3-D electroanatomical mapping to guide the linear ablation
      of left atrium procedure can confirm the isolation of PVPs.

PMID- 17199955
TI  - Impact of right upper pulmonary vein isolation on atrial vagal innervation and
      vulnerability to atrial fibrillation.
AB  - BACKGROUND: Based on the hypothesis that pulmonary vein isolation could result in
      the damage of the epicardial fat pads, this study aimed to investigated the
      impact of right upper pulmonary vein (RUPV) isolation on vagal innervation to
      atria. METHODS: Bilateral cervical sympathovagal trunks were decentralized in 6
      dogs. Metoprolol was given to block sympathetic effects. Multipolar catheters
      were placed into the right atrium (RA) and coronary sinus (CS). RUPV isolation
      was performed via transseptal procedure. Atrial effective refractory period
      (ERP), vulnerability window (VW) of atrial fibrillation (AF), and sinus rhythm
      cycle length (SCL) were measured at RA and distal coronary sinus (CSd) at
      baseline and vagal stimulation before and after RUPV isolation. Serial sections
      of underlying tissues before and after ablation were stained with haematoxylin
      and eosin. RESULTS: SCL decreased significantly during vagal stimulation before
      RUPV isolation (197 +/- 21 vs 13 +/- 32 beats per minute, P < 0.001), but
      remained unchanged after RUPV isolation (162 +/- 29 vs 140 +/- 39 beats per
      minute, P > 0.05). ERP increased significantly before RUPV isolation compared
      with that during vagal stimulation [(85.00 +/- 24.29) ms vs (21.67 +/- 9.83) ms
      at RA, P < 0.001; (90.00 +/- 15.49) ms vs (33.33 +/- 25.03) ms at CSd P < 0.005],
      but ERP at baseline hardly changed after RUPV isolation compared with that during
      vagal stimulation [(103.33 +/- 22.50) vs (95.00 +/- 16.43) ms at RA, P = 0.09;
      (98.33 +/- 24.83) vs (75.00 +/- 29.50) ms at CSd, P = 0.009]. The ERP shortening
      during vagal stimulation after RUPV isolation decreased significantly [(63.33 +/-
      22.51) ms vs (8.33 +/- 9.83) ms at RA, P < 0.005; (56.67 +/- 20.66) ms vs (23.33
      +/- 13.66) ms at CSd, P < 0.05]. AF was rarely induced at baseline before and
      after RUPV isolation (VW close to 0), while VW of AF to vagal stimulation
      significantly decreased after RUPV isolation [(40.00 +/- 10.95) vs 0 ms at RA, P
      < 0.001; (45.00 +/- 32.09) vs (15.00 +/- 23.45) ms at CS, P < 0.05]. The
      architecture of individual ganglia was significantly altered after ablation.
      CONCLUSIONS: The less ERP shortening to vagal stimulation and altered
      architecture of individual ganglia after right upper pulmonary vein isolation
      indicate that isolation may result in damage of the epicardial fat pads, thereby
      attenuating the vagal innervation to atria. The decreased vulnerability window of
      atrial fibrillation indicates that vagal denervation may contribute to its
      suppression.

PMID- 17199956
TI  - Effect of nifekalant on acute electrical remodelling in rapid atrial pacing
      canine model.
AB  - BACKGROUND: Nifekalant may prevent atrial fibrillation (AF) and possibly be
      useful in treatment of atrial tachyarrhythmia in patients with severe heart
      failure. This study investigated the electophysiologic effect of nifekalant on
      the acute atrial remodeling in rapid atrial pacing (RAP) model of canine.
      METHODS: Twelve mongrel dogs subjected to rapid stimulation (400 beats/min) at
      left atrial appendage (LAA) for 24 hours, were randomized into the control group
      (rapid pacing only, n = 6) and the nifekalant group (intravenous nifekalant
      therapy immediately after RAP, n = 6). Atrial electrophysiological parameters
      were measured in right atrium, coronary sinus, LAA, posterior wall of left atrium
      (PWLA) and left superior pulmonary vein (LSPV), before and after the RAP.
      RESULTS: In the control group, the effective refractory periods (ERP) were
      shortened greatly at all sites, paced dogs had substantially shorter ERPs in the
      high right atrium, LAA, and LSPV, but fewer changes in the PWLA, the coefficient
      variation of ERP (COV ERP) was increased significantly. After rapid atrial
      stimulation, the inducibility of AF increased significantly [induction number:
      pre-RAP vs post-RAP, 1.00 +/- 0.89 vs 8.17 +/- 2.79, P < 0.01; duration of AF:
      pre-RAP vs post-RAP, (450.34 +/- 362.59) ms vs (9975.77 +/- 4376.99) ms, P <
      0.01]. In the nifekalant group, although the ERPs were prolonged at all sites
      compared with those in pre-RAP state, only the value at LSPV differed
      significantly from that in pre-RAP state [pre-RAP vs post-RAP, (102.50 +/- 5.24)
      ms vs (132.51 +/- 5.20) ms, P < 0.01]; the COV ERP did not change statistically
      in this group. The inducibility of AF slightly increased but insignificantly
      after pacing [induction number: pre-RAP vs post-RAP, 0.83 +/- 0.75 vs 1.67 +/-
      0.82, P = 0.19; duration of AF: pre-RAP vs post-RAP, (378.67 +/- 317.88) ms vs
      (1124.08 +/- 1109.77) ms, P = 0.06]. Conduction time values did not alter
      significantly in either of the two groups after RAP. CONCLUSIONS: In canine RAP
      model, nifekalant inhibited ERP shortening and ERP heterogeneity increasing,
      decreased AF induction. Nifekalant can reverse acute electrical remodeling effect
      in this model.

PMID- 17199957
TI  - A multi-center study of hemodynamic characteristics exhibited by children with
      unexplained syncope.
AB  - BACKGROUND: Syncope is common in children and adolescents, with 15% estimated to
      have had at least one syncopal episode by age 18. In recent years, an increasing
      number of children, especially girls at their school age, have developed
      unexplained syncope. The mechanism of an unexplained syncope exhibited by
      children is incompletely studied; the association between different hemodynamic
      patterns and clinical features is also not clear. The aim of the study was to
      investigate the hemodynamic patterns of children with unexplained syncope and to
      examine the clinical relevance. METHODS: Two hundred and eight children [87 boys,
      121 girls, aged 3 - 19 years, mean (11.66 +/- 2.72) years] were selectively
      recruited from May 2000 to April 2006 when they presented syncope as their main
      complaint at the Multi-center Network for Childhood Syncope in Beijing, Hunan
      Province, Hubei Province, and Shanghai of China. All of the patients underwent
      head-up tilt tests; data were analyzed using SPSS version 10.0 for Windows.
      Continuous variables were expressed as the mean +/- standard deviation.
      Dichotomous variables were compared through a chi(2) test. A value of P < 0.05
      (two sided) was regarded as statistically significant. RESULTS: The age
      distribution of children with syncope was approximately normal. Head-up tilt
      tests was positive in 155 children, and the incidence of positive response of the
      baseline head-up tilt test for diagnosing unexplained syncope was 50.48%. The
      sensitivity value and diagnostic value of sublingual nitroglycerin head-up tilt
      test were both 74.52%. The hemodynamic pattern was normal in 53 children. The 155
      children, who were positive in head-up tilt tests, showed signs of postural
      orthostatic tachycardia syndrome (60, 28.8%), the vasoinhibitory pattern (72,
      34.6%), the cardioinhibitory pattern (5, 2.4%), and the mixed pattern (18, 8.7%).
      The gender distribution between the two age groups (age < 12 years vs age > or =
      12 years) was not different (P > 0.05). The distribution of hemodynamic patterns
      between the children of the two age groups (age < 12 years vs age > or = 12
      years), and the children with different complaints (dizziness vs syncope) was
      significantly different (P < 0.05), while the distribution between the children
      of different sexes and different lasting time of syncope (< or = 5 minutes vs > 5
      minutes) was not significantly different (P > 0.05). Different hemodynamic
      patterns were differentiated by differing syncope inducements, presymptoms, and
      complicated symptoms during and after syncope. CONCLUSION: The tested girls were
      more prone when compared with the boys to have unexplained syncope, and the peak
      age was around twelve years old. The incidence of positive response of head-up
      tilt tests was also relatively higher for the girls. The distribution of
      hemodynamic patterns for different ages was different. For children with
      unexplained syncope, we should use head-up tilttests to distinguish the
      hemodynamic patterns in order to adopt rational therapeutic measures.

PMID- 17199958
TI  - Deep brain stimulation in the treatment of secondary dystonia.
AB  - BACKGROUND: Dystonia is one of the most challenging movement disorders to treat.
      Medications and surgeries are the two methods to control dystonic symptoms. For
      patients with dystonia in whom symptoms are inadequately controlled with
      pharmacologic measures, the use of deep brain stimulation (DBS) can improve
      symptoms and enhance functional capacity. The best candidate for DBS is believed
      to be primary generalized dystonia, especially the DYT-1 type. Here, we report 9
      cases of secondary dystonia to explore the feasibility, indications and
      complications of DBS in the treatment of secondary dystonia. METHODS: From July
      2003 to June 2006, nine patients with secondary dystonia underwent surgery at
      Beijing Tiantan Hospital. Among them, 2 were diagnosed as having tardive
      dystonia, 1 had posttraumatic dystonia, 3 had a history of perinatal anoxia, 1
      had neonatal pathologic jaundice, and 2 had no exact contributory history; MRI
      showed bilateral lentiform nuclei degeneration in one patient. Six patients
      underwent bilateral subthalamic nucleus (STN)-DBS, two underwent unilateral STN
      DBS, the other underwent left STN and right globus pallidus internus (GPi)-DBS.
      RESULTS: With intraoperative microelectrode recording, the targeted nucleus was
      accurately localized. Tentative stimulation could decrease muscle tension to the
      same extent, but twisting was not obviously improved. Follow-up for 3 months to 3
      years showed satisfactory results in 3 patients with tardive dystonia and
      posttraumatic dystonia and that Burke-Fahn-Marsden Dystonia Scale (BFMS)
      decreased by more than 90%. The improvement of symptoms was progressive along
      with time. The other 6 patients had slight to moderate improvement. None of them
      had severe surgery-related complications. One had lead fracture 16 months after
      surgery and the lead was then evacuated. CONCLUSIONS: DBS could be an ideal
      treatment for patients with tardive and posttraumatic dystonia. For patients with
      perinatal anoxia and diffuse impairment in the basal ganglia, DBS seemed not to
      be a good choice. STN could be an ideal target. Intraoperative microelectrode
      recording and mild amelioration of muscle tension are indicators of correct
      target location. No severe complications occurred.

PMID- 17199959
TI  - Morphological and electrophysiological properties of single myocardial cells from
      Koch triangle of rabbit heart.
AB  - BACKGROUND: The morphological and electrophysiological characteristics of cardiac
      cells in Koch triangle are still disputed. We studied the appearance and
      electrical properties of these diverse myocytes to elucidate their complex
      electrophysiological phenomena. METHODS: Experiments were conducted using cooled
      charge coupling device (CCD) system and whole cell, patch clamp technique to
      determine the morphology, action potential and sodium current density of single
      viable myocytes enzymatically isolated from the Koch triangle of rabbit hearts.
      RESULTS: Morphologically, cardiac cells in shape of spider, tiny spindle, slender
      spindle, rod and strip were observed in percentage of 3.0 +/- 0.3, 35.0 +/- 5.0,
      15.0 +/- 2.0, 40.0 +/- 5.0 and 6.0 +/- 0.7 respectively. The cellular dimensions
      and capacitance gradually increased in the above order (all P < 0.05).
      Electrophysiologically, action potential configurations recorded from them were
      similar respectively to nodal (N), atrial nodal (AN), nodal Hisian (NH), atrial
      (A) and Hisian like potentials obtained from the intact atrioventricular nodal
      preparations. Diastolic depolarization appeared in all myocytes except for rod
      cells. Sodium current density increased in the order of tiny spindle, strip, rod,
      slender spindle cell (all P < 0.05), but could not be detected in spider-shaped
      cells. Linear regression analysis revealed that membrane capacitance was
      correlated negatively to the rate of diastolic depolarization r = -0.70, P <
      0.001, but positively to maximum depolarization potential, amplitude of action
      potential, upstroke velocity and maximum peak value of sodium current density r =
      0.84, 0.80, 0.87 and 0.75, respectively; all P < 0.001. CONCLUSIONS: The results
      demonstrated that spider-shaped, spindle, rod and strip cells in Koch triangle
      might correspond to pacemaking, transitional, atrial and Purkinje like cells,
      respectively. Furthermore, tiny spindle and slender spindle cells were referred
      to transitional cell alpha (TCalpha) and beta (TCbeta) accordingly considering
      their distinctive electrical properties. Different myocytes with diverse
      electrical properties constituted the infrastructure of sophisticated
      electrophysiological phenomena in Koch triangle. In view of the prominent
      percentage and electrical properties, tiny spindle and slender spindle cells were
      presumed to play important roles.

PMID- 17199960
TI  - Natural history of benign prostate hyperplasia.
AB  - BACKGROUND: Benign prostate hyperplasia is one of the most common diseases
      affecting the health of the aging males. Watchful waiting is an acceptable
      management strategy for benign prostate hyperplasia in which the patient is
      monitored by the physician but receives no active intervention. The
      epidemiological data on this are lacking in China. Our study was designed to
      evaluate the changes of signs and symptoms of patients with benign prostate
      hyperplasia during management by watchful waiting in China. METHODS: One hundred
      and forty-five patients with benign prostate hyperplasia aged > 50 years were
      enrolled in management by watchful waiting. All the patients were visited every 6
      months and were given an International Prostate Symptom Score and Quality of Life
      questionnaire to complete. They also had uroflowmetry and were assessed using
      ultrasonography to get the volume of prostate, transition zone and amount of
      residual urine. The Student's t test, the Chi-square test, and variance analysis
      were used in the statistical analysis. RESULTS: All patients were visited after 6
      months, the mean volume of transitional zone was found to have increased by 1.6
      ml (P < 0.01), International Prostate Symptom Score was increased by 0.8 (P <
      0.01) and Quality of Life was increased by 0.2 (P < 0.01), and there was no
      statistical change in other data. Among these patients, 17.9% (26/145) visited
      again after 12 months when the data failed to show a statistically significant
      difference among the three groups (0, 6, and 12 months). CONCLUSIONS: After one
      year's follow-up, the progression of benign prostate hyperplasia was slow and the
      clinical data did not undergo much change.

PMID- 17199961
TI  - Strong additive effect of calcitriol and cyclosporine A on lymphocyte
      proliferation in vitro and rat liver allotransplantations in vivo.
AB  - BACKGROUND: Vitamin D3 and its metabolites have been found to exert
      immunosuppressive effects both in vivo and in vitro. We investigated the
      synergistic effect of calcitriol and cyclosporine A (CsA) on lymphocyte
      proliferation in vitro and graft rejection following rat liver
      allotransplantations in vivo. METHODS: Alloantigen driven, human peripheral
      mononuclear cells' proliferation and cytokine production capacity were tested in
      the presence or absence of various concentrations of calcitriol or CsA. In vivo,
      liver allografts were transplanted in a high responder strain combination (SD to
      Wistar) rats and combination of subtherapeutical dose of CsA and calcitriol was
      administered in recipients, whereas the control recipients received single or no
      immunosuppressant. Proliferation of splenocyte from recipient was tested with
      mixed lymphocyte reaction. Serum interleukin-2 (IL-2) and interferon gamma (IFN
      gamma) concentrations were measured with enzyme linked immunosorbent assay.
      RESULTS: Combined medication of 10(-9) mol/L calcitriol and 100 ng/ml CsA
      inhibited human peripheral mononuclear cells' proliferation to alloantigen and
      the production of IL-2 and IFN-gamma but promoted that of IL-4 and IL-10.
      Similarly, combination of 250 ng x g(-1) x d(-1) calcitriol and 1.0 mg x g(-1) x
      d(-1) CsA showed an additive effect in liver transplant model. It restrained
      splenocyte proliferation to alloantigen from donor and significantly reduced
      serum concentration of IL-2 and IFN-gamma in recipients. Consequently, allograft
      rejection in combined medication group was minor (median William's grade was 1.0
      vs 3.0 in combined medication group and in the control group, P < 0.05) and the
      recipients' survival was evidently prolonged [(93.7 +/- 5.8) days vs (12.6 +/-
      1.4) days in combined medication group and in the control group, P < 0.01].
      CONCLUSION: A combination of calcitriol and CsA has an additive effect on
      limiting lymphocyte proliferation and prolonging liver graft survival. With its
      additional immunomodulating property, calcitriol is a potent immunosuppressant
      that can extend the therapeutic window of classical immunomodulators in
      prevention and treatment of liver graft rejection.

PMID- 17199962
TI  - Transplantation of human amniotic epithelial cells improves hindlimb function in
      rats with spinal cord injury.
AB  - BACKGROUND: Human amniotic epithelial cells (HAECs), which have several
      characteristics similar to stem cells, therefore could possibly be used in cell
      therapy without creating legal or ethical problems. In this study, we
      transplanted HEACs into the injured spinal cord of rats to investigate if the
      cells can improve the rats' hindlimb motor function. METHODS: HAECs were obtained
      from a piece of fresh amnion, labeled with Hoechst33342, and transplanted into
      the site of complete midthoracic spinal transections in adult rats. The rats (n =
      21) were randomly divided into three groups: Sham-operation group (n = 7), cells
      graft group (n = 7), and PBS group (n = 7). One rat of each group was killed for
      histological analysis at the second week after the transplantation. The other six
      rats of each group were killed for histological analysis after an 8-week
      behavioral testing. Hindlimb motor function was assessed by using the open-field
      BBB scoring system. Survival rate of the graft cells was observed at second and
      eighth weeks after the transplantation. We also detected the myelin sheath fibers
      around the lesions and the size of the axotomized red nucleus. A one-way ANOVA
      was used to compare the means among the groups. The significance level was set at
      P < 0.05. RESULTS: The graft HAECs survived for a long time (8 weeks) and
      integrated into the host spinal cord without immune rejection. Compared with the
      control group, HAECs can promote the regeneration and sprouting of the axons,
      improve the hindlimb motor function of the rats (BBB score: cells-graft group 9.0
      +/- 0.89 vs PBS group 3.7 +/- 1.03, P < 0.01), and inhibit the atrophy of
      axotomized red nucleus [cells-graft group (526.47 +/- 148.42) microm(2) vs PBS
      group (473.69 +/- 164.73) microm(2), P < 0.01]. CONCLUSION: Transplantation of
      HAECs can improve the hindlimb motor function of rats with spinal cord injury.

PMID- 17199963
TI  - Immunologic mechanisms and treatment of acute coronary syndromes.

PMID- 17199964
TI  - Tong-xie-ning, a Chinese herbal formula, in treatment of diarrhea-predominant
      irritable bowel syndrome: a prospective, randomized, double-blind, placebo
      controlled trial.

PMID- 17199965
TI  - Thrombomodulin gene polymorphism and thrombomodulin expression in essential
      hypertension.

PMID- 17199966
TI  - Comparison of the extraperitoneal and transperitoneal laparoscopic radical
      prostatectomy.

PMID- 17199968
TI  - Congenital insensitivity to pain with anhidrosis and progressing acro-osteolysis:
      a case report with 7-year follow-up.

PMID- 17199967
TI  - Cardiac ryanodine receptor gene (hRyR2) mutation underlying catecholaminergic
      polymorphic ventricular tachycardia in a Chinese adolescent presenting with
      sudden cardiac arrest and cardiac syncope.

PMID- 17199969
TI  - Recurrent perimedullary arteriovenous fistula at thoracic level.

PMID- 17199971
TI  - [Helicobacter pylori re-study topics for the future].

PMID- 17199972
TI  - [Evidence-based medicine on the relationship between Helicobacter pylori and
      gastroesophageal reflux disease].

PMID- 17199973
TI  - [Effects of Helicobacter pylori and Helicobacter pylori-related cytokines on
      apoptosis of gastric epithelial cells and mechanisms thereof].
AB  - OBJECTIVE: To investigate the influence of Helicobacter pylori (H. pylori) and H.
      pylori-related cytokines on the apoptosis of gastric epithelial cells and
      mechanisms thereof. METHODS: (1) Human gastric cancer cells of the line AGS and
      human gastric epithelial cells of the line GES-1 were cultured as control group,
      or incubated with H. pylori alone or H. pylori in combination with exogenous
      cytokines: interleukin (IL)-1beta, IL-8, or IL-10 for 24 hours. Then flow
      cytometry (FCM) was used to determine the rate of apoptosis. (2) The GES-1 and
      AGS cells were incubated with H. pylori for 24 hours and exogenous cytokines for
      2 hours respectively. Then RT-PCR was used to examine the level of Fas mRNA
      expression. (3) Another GES-1 and AGS cells were cultured as control group, or
      incubated with FasL alone or FasL + exogenous cytokine for 2 hours (incubated
      with IL-1beta, IL-8, or IL-10 for 2 hours before being added with FasL). Then FCM
      was used to detect the apoptosis rate. RESULTS: (1) In comparison to the
      apoptosis level of control group, H. pylori induced an increase in the apoptosis
      rate of GES-1 and AGS cells by 113.0% and 47.0% respectively (both P < 0.05). The
      H. pylori-induced apoptosis rates of GES-1 cells (by 29.6% or 25.8%) and AGS
      cells (by 19.7% or 21.1%) were reduced by IL-1beta or IL-10 (all P < 0.05). IL-8
      increased the H. pylori-induced apoptosis level of GES-1 cells by 19.9% (P <
      0.05). (2) In the baseline status, both GES-1 and AGS cells showed Fas mRNA
      expression. The Fas mRNA expressions of the GES-1 and AGS cells incubated with H.
      pylori were increased by 89.0% and 36.0% respectively (both P < 0.05) in
      comparison to that of the control group. IL-1beta and IL-10 had no significant
      effect on the basal Fas mRNA expressions in both GES-1 and AGS cells (all P >
      0.05). IL-8 up-regulated the basal Fas mRNA expression level of the GES-1 cells
      by 33.0% (P < 0.05). (3) IL-1beta and IL-10 inhibited the FasL-induced apoptosis
      rate of the GES-1 cells (by 30.3% and 32.5% respectively) and AGS cells (by 44.2%
      and 51.5% respectively) (all P < 0.05). IL-8 enhanced the FasL-induced apoptosis
      level of the GES-1 cells by 100% (P < 0.05). CONCLUSION: The gastric epithelium
      apoptosis induced by H. pylori may be in association with Fas receptor. IL-8 may
      enhance the H. pylori-induced apoptosis by up-regulating the Fas receptor
      expression. IL-1beta and IL-10 may modulate the apoptosis through other
      mechanisms.

PMID- 17199974
TI  - [The roles of Helicobacter pylori and pattern of gastritis in the pathogenesis of
      reflux esophagitis].
AB  - OBJECTIVE: Comparing the infection rates and density of Helicobacter pylori (H.
      pylori) and the patterns of gastritis in reflux esophagitis (RE) and non-erosive
      reflux disease (NERD) patients to investigate the role of H. pylori in the
      pathogenesis of RE. METHODS: Two hundred and twenty-three out-patients with
      typical gastroesophageal reflux symptoms who consecutively visited the hospital
      underwent ambulatory 24-hour pH monitoring and gastroscopy, and biopsy of the
      gastric mucosa. RE and NERD were diagnosed based on the presentation of
      endoscopy. Gastritis was divided into four different patterns: chronic non
      atrophic antritis (CNAA); chronic non-atrophic pan-gastritis (CNAG); chronic
      atrophic antritis (CAA); and chronic atrophic pan-gastritis (CAG). H. pylori
      infection was evaluated by Warthin-Starry staining. DeMeester score > or = 15 was
      considered as pathological acid reflux. RESULTS: Sixty-two patients (27.8%) were
      found to have RE, 161 (72.2%) were found to have NERD. Totally, 67 patients had
      H. pylori infection (30.0%). There was no significant difference in H. pylori
      infection rate between the RE and NERD groups (25.8% vs. 31.5%, P > 0.05). 45 of
      the 223 patients were diagnosed as with CNAA (20.2%), 88 (39.5%) with CNAG, 65
      (29.2%) with CAA, and 25 (11.2%) with CAG. The CAG rates in the RE and NERD
      groups were 6.5% and 13.0% respectively (P > 0.05). There were no differences in
      abnormal pH monitoring rate and DeMeester score among the different patterns of
      gastritis. In the sixty-seven H. pylori-positive GERD patients, the 24 h pH
      monitoring positive rate of the moderate-severe H. pylori colonization density
      group was 46.4%, significantly higher than that of the mild H. pylori
      colonization density group (73.5%, P < 0.05); and the mean intra-gastric pH value
      during 24 hours of the moderate-severe H. pylori colonization density group was
      2.3 +/- 0.8, significantly higher than that of the mild H. pylori colonization
      density group (2.0 +/- 1.1, P < 0.05). CONCLUSION: H. pylori infection is
      associated with the pattern of gastritis, but shows no relationship to the
      incidence of RE. High density of H. pylori colonization in gastric corpus may
      reduce the esophageal acid exposure. Diffuse atrophic gastritis may protect the
      patients from RE.

PMID- 17199976
TI  - [Influence of resistance of Helicobacter pylori to antibiotics on the
      Helicobacter pylori eradication regimens].
AB  - OBJECTIVE: To investigate the influence of resistance of Helicobacter pylori (H.
      pylori) to antibiotics on the efficacy of lansoprazole triple therapy for H.
      pylori eradication. METHODS: 157 patients, 102 males and 55 females, aged 42.7
      (18 - 70), with upper abdominal symptoms, 59 with chronic gastritis and 98 with
      peptic ulcer, underwent gastroendoscopy 157 H. pylori strains were isolated from
      the gastric biopsy specimens of these patients and cultured. Minimal inhibitory
      concentrations of 3 antibiotics (metronidazole and clarithromycin) were
      determined by E-test. The 157 patients were treated by triple therapies,
      including lansoprazole, metronidazole, and clarithromycin for 7 days.
      Reexamination was done at least 4 weeks after the therapy. RESULTS: The
      resistance rates of H. pylori to metronidazole and clarithromycin were 45.9%
      (72/157) and 18.5% (29/157) respectively. The reexamination showed an eradication
      rate of H. pylori of 61.8% (97/157). The eradication rates of the metronidazole
      sensitive and resistant strains were 89.4% (76/85) and 29.2% (21/72) respectively
      (P < 0.01), and the eradication rates of the clarithromycin-sensitive and
      resistant strains were 72.7% (93/128) and 16.0% (4/29) respectively (P < 0.01).
      Presence of a gastroduodenal ulcer, age and gender did not differ significantly
      between the eradicated and non-eradicated groups (all P > 0.05). CONCLUSION:
      Resistance of H. pylori to antibiotics is the most important cause of the failure
      of H. pylori eradication.

PMID- 17199978
TI  - [Difference analysis on proteome of Helicobacter pylori in patients with peptic
      ulcer, gastritis, and gastric cancer].
AB  - OBJECTIVE: To identify the different proteins of Helicobacter pylori (H. pylori)
      in gastric cancer, peptic ulcer, and gastritis initially. METHODS: H. pylori in
      the endoscopic biopsy specimens of gastric mucosa of patients with gastric
      cancer, peptic ulcer, or gastritis, 3 specimens for each disease, were separated
      and cultured. The whole-cell protein of the H. pylori was extracted by lysis
      buffer and sonication. The protein concentration of the bacteria cell lysates was
      measured by the Bradford method. The protein maps of H. pylori were obtained by
      two-dimensional gel electrophoresis (2-DE) and the different proteins in gastric
      cancer, peptic ulcer and gastritis were analyzed by Image Master v 5.0. Matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI
      Q-TOF-MS) were performed to identify the different proteins. The differential
      proteins were searched by the Mascot database at www.matrixscience.com. RESULTS:
      Four protein spots of H. pylori were over-expressed in the protein maps from
      gastric cancer in comparison with those from peptic ulcer and gastritis. Mass
      identification showed that the 4 proteins were thioredoxin, adenylate kinase,
      single-stranded DNA-binding protein, and ribosomal protein 50S L7/L12, with the
      Mowse scores of 94, 286, 139 and 132, and with the sequence coverage rates of
      77%, 33%, 33%, and 28% respectively. CONCLUSION: Anti-oxidant and inhibiting
      apoptosis, thioredoxin may be related to gastric carcinogenesis induced by H.
      pylori. Proteomics technology has a widespread perspective in the field of
      relationship between pathogenic bacteria and gastric cancer.

PMID- 17199977
TI  - [Expression of peroxisome proliferators-activated receptor-gamma and
      cyclooxygenase-2 in Helicobacter pylori infection-associated diseases and
      significance thereof].
AB  - OBJECTIVE: To investigate the expression of peroxisome proliferators-activated
      receptor-gamma (PPAR-gamma) and cyclooxygenase-2 (COX-2) in Helicobacter pylori
      (Hp)-associated gastric mucosal lesions and the relations among them. METHODS:
      Two-step immunohistochemical staining was used to detect the expression of PPAR
      gamma and COX-2 proteins in the gastric biopsy specimens from 209 patients with
      lesions of gastric mucosa, including 75 cases of chronic superficial gastritis
      (CSG), 24 cases of chronic atrophic gastritis (CAG), and 90 cases of intestinal
      metaplasia (MI) and dysplasia (DYS), and from 20 subjects with normal gastric
      mucosa negative in Hp as controls. In addition, 36 CSG patients were followed up
      for 10 years to observe the changes of expression of PPAR-gamma and COX-2.
      RESULTS: (1) The expression of COX-2 protein in the glandular cells of the CSG,
      CAG, and IM + DYS groups were 42.7%, 45.8%, and 61.1% respectively, all
      significantly higher than that of the control group (20%, P < 0.01 or 0.05). The
      expression of COX-2 protein in the inflammatory cells of the CSG, CAG, and IM +
      DYS groups were 32%, 29.2%, and 36.7% respectively, all significantly higher than
      that of the control group (0%, all P < 0.05). (2) In the CSG and IM + DYS groups
      the expression levels of COX-2 in both the inflammatory and glandular cells were
      both significantly higher in the Hp-positive patients than in the Hp-negative
      patients (P < 0.05 or 0.01). (3) The expression of PPAR-gamma protein in the
      glandular cells of the CSG, CAG, and IM + DYS groups were 18.7%, 29.2%, and 45.6%
      respectively, all significantly higher than that of the control group (0%, all P
      < 0.01); and the expression levels of PPAR-gamma protein in the inflammatory
      cells of the CSG, CAG, and IM + DYS groups were 22.5%, 20.8%, and 22.2%
      respectively, all significantly higher than that of the control group (0%, P <
      0.05 or 0.01). (4) In the CSG and IM + DYS groups the expression levels of PPAR
      gamma in the inflammatory cells of the Hp-positive patients were both
      significantly higher than those of the Hp-negative patients (both P < 0.01); and
      the. expression levels of PPAR-gamma in the glandular cells of the Hp-positive
      patients were both significantly higher than those of the Hp-negative patients
      (both P < 0.01). (5) The expression level of COX-2 in the inflammatory cells of
      the CSG patients with a persistent Hp infection after a period of ten years was
      33.3%, significantly lower than that a decade before (38.9%, P < 0.05). However,
      the expression level of PPAR-gamma in the inflammatory cells of the patients with
      a persistent Hp infection after a period of ten years was 30.6%, not
      significantly different from that a decade before (33.3%, P > 0.05). (6) The
      expression levels of COX-2 and PPAR-gamma in the glandular cells of the CSG
      patients with a persistent Hp infection after a period of ten years were 55.6%
      and 30.6% respectively, both significantly higher than those a decade before
      (47.2% and 22.2%, both P < 0.01). (7) In all Hp-negative disease groups the
      expression level of COX-2 in the inflammatory cells was not significantly
      correlated with the expression level of PPAR-gamma in the inflammatory cells(r =
      0.006 and 0.149, P > 0.05) In the Hp-negative disease groups, the expression
      level of COX-2 in the glandular cells was significantly positively correlated
      with the expression level of PPAR-gamma in the glandular cells in the IM + DYS
      group (r = 0.336, P < 0.05), however, not significantly correlated with the
      expression level of PPAR-gamma in the glandular cells in both CAG and CSG groups
      (r = 0.035 and 0.126, both P > 0.05). (8) In both the inflammatory cells and
      glandular cells the COX-2 expression was significantly positively correlated with
      the PAR-gamma expression in all disease groups with Hp positivity (r = 0.348 and
      0.645, P < 0.05 or 0.01). CONCLUSION: (1) Hp infection induces the overexpression
      of COX-2 and PPAR-gamma in the inflammatory and glandular cells within gastric
      mucosa, thus participating in the pathogenesis of gastric cancer (2) The
      expression of COX-2 induces by Hp is related to acute inflammation caused by Hp
      infection. In the glandular cells, significant increase of COX-2 and PPAR-gamma
      expression implies that along with time the expression of COX-2 and PPAR-gamma
      may change in advance of the morphological changes of the gastric mucosa.

PMID- 17199981
TI  - [Effects of fusion gene encoding the hVEGF165 and fused hirudin on restenosis of
      injured carotid artery induced by angioplasty].
AB  - OBJECTIVE: To study the effects of fusion gene encoding the hVEGF(165) and fused
      hirudin on restenosis of injured carotid artery. METHODS: A fusion gene encoding
      hVEGF(165) and fused hirudin (hVEGF(165)-FH) was constructed and clone into the
      eukaryotic expression vector pcDNA3.0, thus constructing the plasmid VEGF(165)
      FH/pcDNA3.0. Its activities to stimulate endothelial cell proliferation and to
      inhibit thrombosis were identified. Sixteen New Zealand rabbits underwent
      ligation of external carotid artery and a balloon was inserted into the common
      carotid artery for 30 minutes so as to construct model of restenosis of injured
      carotid artery. Then the rabbits were randomly divided into 4 equal groups. In
      the one-week and 3-week control groups, 400 microg of DNA of the plasmid pcDNA3.0
      were transfused into the arterial lumen at the injured part immediately after the
      angioplasty, and 400 microg of DNA of the plasmid VEGF(165)-FH/pcDNA3.0 were
      transfused in the 1-week and 3-week experimental groups. One week and 3 weeks
      after the treatment peripheral blood samples were collected to detect the
      activated partial thromboplastin time (APTT), thrombin time (TT), and platelet
      aggregation rate, and then the rabbits underwent angiography to observe the
      situation of restenosis. Then the rabbits were killed to take out the injured
      part of artery to undergo pathological examination and Western blotting. RESULTS:
      The values of APTT, TT, and platelet aggregation rate were not significantly
      different among the 4 groups. Angiography conducted 1 and 3 weeks later showed
      that restenosis was significantly mild in the 2 experimental groups in comparison
      with the 2 control groups, and severe restenosis was seen in the 3-week control
      group. Western blotting showed that expression of specific fused protein could be
      found in the 1-week and 3-week experimental group, the amount of the latter group
      being less than that of the former group; however, no expression of specific
      fused protein was found in the 2 control groups. Pathological examination showed
      that the narrowing of lumen 1-week and 3-week experimental groups were 11.50% and
      19.75%, both significantly milder than those of the 1-week and 3-week control
      groups (33.25% and 52.25% respectively, both f P < 0.05). VB staining showed that
      the (intima/media (I/M) ratio of the 1-week and 3-week experimental groups were
      0.12 and 0.35 respectively, both significantly lower than those of the 2 control
      groups (0.50 and 1.07 respectively, both P < 0.05). CONCLUSION: Accelerating re
      endothelialization and inhibiting thrombosis, the fused gene hVEGF(165)-FH
      effectively prevents restenosis after angioplasty, On the basis of endothelial
      repair, construction of fused genes with double even multiple targets may be a
      novel and potential therapeutic approach for restenosis after percutaneous
      coronary intervention.

PMID- 17199982
TI  - [Effects of chronic HBV infection on human hepatic cytochrome P450 3A4].
AB  - OBJECTIVE: To study the effect of HBV on human hepatic cytochrome P450 3A4
      (CYP3A4) in patients with chronic HBV infection. METHODS: Liver tissue samples
      were obtained from 21 patients undergoing hepatic surgery with (n = 10) or
      without (n = 11) chronic HBV infection and were homogenized, then hepatic
      microsomes were separated from the homogenate using a differential centrifugation
      method. The activity of CYP3A4 was determined by HPLC, and the expression of
      CYP3A4 protein was determined by Western-blotting. RESULTS: The V(max) of CYP3A4
      in patients with chronic HBV infection was 493 +/- 297 pmol/min/mg, significantly
      reduced (P = 0.03) comparing to the normal control group: 741 +/- 189
      pmol/min/mg. Western-blotting showed the the CYP3A4 protein expression in
      patients with chronic HBV infection was 3.04 +/- 1.63, which was significantly
      lower than that of the normal control group: 5.67 +/- 1.52 (P = 0.003). In
      contrast, no significant alteration of the K(m) of CYP3A4 was observed between
      two groups: 0.142 +/- 0.057 micromol/L; 0.121 +/- 0.024 micromol/L (P = 0.103).
      The enzymatic activity and protein expression of each liver sample had a high
      correlation. Correlation index was 0.7683 (P < 0.001). CONCLUSION: Chronic HBV
      infection tends to down-regulate the expression of hepatic CYP3A4 and reduce its
      activity, but does not affect its structure. When patients with chronic HBV
      infection are given drugs metabolized by CYP3A4, the drugs' side-effects brought
      by the variation of their metabolism should be taken into account.

PMID- 17199983
TI  - [Evaluation of the four simple methods in the diagnosis of diabetic peripheral
      neuropathy].
AB  - OBJECTIVE: To evaluate the efficacy of neuropathy symptom score/neuropathy
      disability score (NSS/NDS), Michigan Neuropathy Screening Instrument (MNSI),
      vibration perception threshold (VPT) and 24010 g monofilament examination in the
      diagnosis of diabetic peripheral neuropathy (DPN). METHODS: 240 patients with
      type 2 diabetes underwent the 4 simple tests: NSS/NDS, MNSI, VPT, and 10 g
      monofilament examination and nerve conduction velocity (NCV) examination. Using
      the results of NCV as golden criteria, the sensitivity, specificity, positive and
      negative predictive values, accuracy and kappa values of these tests were
      analyzed. RESULTS: The sensitivity, specificity, accuracy, and kappa value of
      MNSI score over 2 were 78.15%, 88.43%, 83.33%, and 0.67 respectively. The
      validity could be ranked in the following order with respect to the diagnosis of
      DPN: MNSI > VPT > NSS/NDS > 10 g monofilament examination. CONCLUSION: MNSI is a
      rapid, simple and reliable test for screening DPN in both diabetes clinics and
      epidemiological surveys.

PMID- 17199984
TI  - [Curative effects of cyclosporin A therapy upon myelodysplastic syndrome].
AB  - OBJECTIVE: To evaluate the efficacy of cyclosporin A (CsA) in treatment of
      myelodysplastic syndromes (MDS). METHODS: Thirty-three patients with MDS,
      including refractory anemia (RA, n = 24), refractory anemia with ringed
      sideroblasts (RAS, n = 2), and refractory anemia with excess blasts (RAEB, n =
      7), 23 males and 10 females, aged 46 (6 approximately 71), hospitalized in 4 CsA,
      grade 3 hospitals in Beijing who failed to respond to folic acid and vitamin B12,
      received CsA 3 approximately 5 mg x kg(-1)x d(-1), 2 times per days, taken orally
      in 2 separate doses for at least 3 months (2 approximately 27 months). During the
      course of treatment the dosage was adjusted according to the CsA blood
      concentration and curative effect. Follow-up was conducted for 14 months on
      average. The curative effect of those who took CSA for more than 2 months
      underwent statistical analysis, and for those who took CSA for less than 2 months
      only the side effects underwent statistical analysis. RESULTS: After 3 months of
      the treatment, the hematological improvement (HI) was observed in 18 of the 32
      evaluative patients (56.3%) by the criteria of the International Working Group
      (IWG). At the end of the follow-up 4 patients showed alteration of disease
      progression, including 1 case of complete remission (CR) and 3 cases of partial
      remission (PR), and 16 patients showed homological improvement, responders
      numbering 20 totally, with a response rate of 62.5% (20/32). One of the 20
      patients respondent to CsA died and 7 of the 12 patients who failed to respond to
      CsA died. CONCLUSION: Improving the clinical manifestations and lengthening the
      survival time, CsA therapy is effective in the patients with RA or RAEB, and both
      hypoplastic bone marrow and hyperplastic bone marrows respond to the therapy. CsA
      therapy is potentially the most effective therapy for MDS.

PMID- 17199985
TI  - [Down-regulation of expression of survivin and induction of apoptosis in the
      human Burkitt lymphomas cells by ligation of CD40-CD40L].
AB  - OBJECTIVE: To study the biological effects of ligation of CD40 mediated by
      soluble recombinant human CD40 ligand (srhCD40L) on the human malignant
      hematogenous cells and to explore the molecular mechanism thereof. METHODS: Human
      Burkitt lymphoma cells of the line CA46 were cultured. Flow cytometry was used to
      detect the expression of CD40 molecule on the cell surface. CA46 cells were put
      into 96-well plate and added with solutions of srhCD40L of the terminal
      concentrations of 0.04 microg/ml, 0.2 microg/ml, 1.0 microg/ml, and 5.0 microg/ml
      respectively, and 24, 28, 72, 96, and 120 hours later cell growth curve was
      drawn. MTT assay was used to other CA46 cells co-incubated with srhCD40L of the
      terminal concentrations of 0.04 microg/ml, 0.2 microg/ml, 1.0 microg/ml, and 5.0
      microg/ml respectively so as to calculate the proliferation inhibition rate. CA46
      cells were treated with srhCD40L of the concentrations of 1.0 microg/ml for 24,
      48, and 72 hours respectively, FCM was used to analyze the DNA cycle and TUNEL
      was used to calculate the apoptotic rate. Annexin-V labeling method was used to
      detect the positive rate of apoptotic cells. CA46 cells were treated with
      srhCD40L of the concentration of 1 microg/ml for 24, 48, 72, or 96 hours, semi
      quantitative RT-PCR was used to detect the mRNA expression of survivin, an anti
      apoptosis protein, and the protein expression of survivin was detected by Western
      blotting. RESULTS: The expression rate of CD40 in the human Burkitt CA46 cells
      was 99%. srhCD40L dose-dependently inhibited the proliferation of the CD46 cells.
      Treated by srhCD40L, the progress of cells at S stage into G(2)/M stage was
      inhibited. TUNEL showed that treated by srhCD40L (1.0 microg/ml) for 24, 48, and
      72 hours the apoptotic rates of the cells were 9%, 18%, and 35% respectively.
      Annexin-V showed that after incubation with srhCD40L (1.0 microg/ml) for 24 h the
      apoptotic rate was 10.04%. Two apoptotic peaks appeared 48 and 72 hours later.
      Semi-quantitative RT-PCR and Western blotting showed that the survivin mRNA
      expression and protein expression were both down-regulated. CONCLUSION: Ligation
      of CD40 by srhCD40L inhibits the proliferation of malignant hematogenous cells
      and induces their apoptosis. Expression of survivin mRNA and protein may be
      related to cell growth inhibition and to the apoptosis mediated by Ligation of
      CD40 by srhCD40L.

PMID- 17199986
TI  - [Binding fistulojejunostomy for the treatment of external pancreatic fistula].
AB  - OBJECTIVE: To evaluate the safety and feasibility of binding fistulojejunostomy,
      a new operative procedure, in the treatment of external pancreatic fistula.
      METHODS: Eight patients suffering from external pancreatic fistula, 4 males and 4
      females, aged 49 (22 approximately 69), underwent binding fistulojejunostomy: 2
      cm-length of fistula was isolated and a tube was inserted therein, the jejunum
      was transected and the distant cut end was everted for the length of 3 cm, the
      mucosa of the everted jejunum was destroyed with carbolic acid, the everted
      mucosa of jejunum and the fistula were brought together and sutured with silk,
      the everted jejunum was then turned back to wrap over the fistula, a silk tie was
      lopped around the entire circumference of the anastomosis, and lastly, the tube
      was led out of the abdominal wall. RESULTS: all 8 patients recovered smoothly
      without pancreatic leakage and other complications. CONCLUSION: Binding
      fistulojejunostomy is safe and effective for the treatment of external pancreatic
      fistula.

PMID- 17199991
TI  - [Prognostic factors of myasthenic crisis after extended thymectomy in patients
      with generalized myasthenia gravis].
AB  - OBJECTIVE: To investigate the prognostic factors of myasthenic crisis after
      extended thymectomy in patients with generalized myasthenia gravis (MG). METHODS:
      Extended thymectomy was performed on 176 patients with generalized MG, 74 males
      and 102 females, aged 4 - 67, of which 36 experienced postoperative myasthenic
      crisis and required prolonged mechanical ventilation. The relations among the
      age, sex, preoperative course of disease, pathologic type of thymus, Osserman
      classification, history of infection during 1 month preoperatively, history of
      myasthenic crisis 1 month preoperatively, thymoma, preoperative daily dose of
      pyridostigmine, preoperative steroid use, operation time, intra-operative blood
      loss, and intra-operative pleura injury and postoperative myasthenia crisis were
      analyzed. RESULTS: Univariate analysis showed that bulbar symptoms (OR = 8.494, P
      = 0.001), history of myasthenic crisis 1 month preoperatively (OR = 5.667, P =
      0.000), thymoma (OR = 2.147, P = 0.047), Osserman types III and IV (OR = 0.459, P
      = 0.000), history of infection during 1 month preoperatively (OR = 3.30, P =
      0.038), large pre-operative dose of pyridostigmine (OR = 1.019, P = 0.001), long
      operation time (OR = 1.012, P = 0.034), and more blood loss (186 ml +/- 163 ml)
      (OR = 1.004, P = 0.012), were all prognostic factors or postoperative myasthenic
      crisis. However, multivariate logistic regression analysis revealed that
      preoperative bulbar symptoms (OR = 7.709, P = 0.003), history of infection during
      1 month preoperatively (OR = 4.582, P = 0.037), history of myasthenic crisis 1
      month preoperatively (OR = 4.526, P = 0.001, large pre-operative dose of
      pyridostigmine (OR = 1.016, P = 0.001) were prognostic factors of postoperative
      myasthenic crisis. CONCLUSION: Preoperative bulbar symptoms, history of
      preoperative myasthenic crisis, history of preoperative infection, and large
      preoperative dose of, pyridostigmine are all independent influencing factors of
      postoperative myasthenic crisis. Ample preoperative care may prevent
      postoperative myasthenic crisis in the patients with such factors.

PMID- 17199992
TI  - [Clinical outcomes of treatment of glenohumeral osteoarthritis with new
      generation shoulder prosthesis].
AB  - OBJECTIVE: To investigate the clinical effects of arthroplasty with UNIVERS 3-D
      prosthesis, the representative of fourth generation of shoulder joint prosthesis
      proved to be more suitable to shoulder anatomy, in treatment of glenohumeral
      osteoarthritis. METHODS: Seventy-four patients with glenohumeral osteoarthritis,
      aged 67.07 (47 - 84), received shoulder arthroplasty with UNIVERS 3-D prosthesis
      and were followed up for 31.9 months (12 - 74 months). Roentgenography was
      conducted to observe the acromion, and acromion-humeral distance (AHD),
      glenohumeral distance (GHD), humerus height (HH), and humerus width (HW).
      Constant scoring and normalized Constant scoring were used to evaluate the
      function of the shoulder joint. RESULTS: The Constant score at the last follow-up
      was 68.40 +/- 16.91 points, significantly higher than that at beginning (34.094
      +/- 15.00, P < 0.05), The normalized Constant score at the last follow-up was
      92.27 +/- 22.53%, significantly higher than that at the beginning (45.29 +/-
      19.87%, P < 0.05). The post-operative pain, daily life, activity score, and
      myodynamia scores were all significantly higher than those evaluated pre
      operatively (all P < 0.05). Pre-operative roentgenography showed 93.47% of the
      cases with humeral head periarticular osteophytes located at the inferior side;
      36.96% with humeral head necrosis; 8.69% with humeral head cyst; and 39.13% with
      periarticular osteophytes of glenoid, and showed that AHD was shortened (1.83 +/-
      1.64 mm), and GHD, HH, and HW were all narrowed (10.91 +/- 3.03 mm; 5.71 +/- 4.32
      mm, and 3.34 +/- 4.82 mm respectively). After the operation, the AHD, GHD, and HH
      were all significantly increased, and HW did not significantly changed. The
      humeral inclination angle was changed postoperatively from 126 degrees to 142
      degrees. The incidence of radiolucent lines around the prosthesis of humeral
      shaft was 5.41%, most in the zones d, c, and e, all with the radiolucent index of
      less than 1. The overall complication rate was 12.2%. CONCLUSION: Treatment of
      glenohumeral osteoarthritis with UNIVERS 3-D prosthesis effectively reconstructs
      the anatomy of glenohumeral joint, and shows excellent clinical results with low
      incidence of radiolucency and postoperative complications.

PMID- 17199993
TI  - [Identification of the differentially expressed genes between primary breast
      cancer and paired lymph node metastasis through combining mRNA differential
      display and gene microarray].
AB  - OBJECTIVE: To identify and clone the genes related to breast cancer metastasis
      through comparing the mRNA expression profiling between primary breast cancer and
      paired lymph node metastasis. METHODS: First, primary breast cancer cells and
      paired lymph node metastasis tissues were used to identify their differentially
      expressed genes by using mRNA differential display, and fragments of
      differentially expressed genes were obtained by gel cutting and cloning to pGEM-T
      vector, then sequencing and blasting with the GenBank for their homologous genes.
      Then, the obtained genes were validated by using reverse dot blot hybridization
      and gene microarray. Finally, the mRNA expression levels in the 7 breast cancer
      cell lines with different metastasis behaviors were detected by real-time RT-PCR.
      RESULTS: The mRNA expression profiling of the metastatic breast cancers in lymph
      node was similar to that of their primary cancers. 16 differentially expressed
      gene fragments were obtained from mRNA differential display; four of them were
      found to be unknown genes, and had been accepted by the GenBank, with the
      accession numbers BG518428, BG518429, BM005520, and BM005521. Of the other 12
      genes, 8 were known genes, and 4 were genes with known sequences but unknown
      functions. The kinesin-like DNA binding protein (KNSL4) and dihydropyrimidine
      dehydrogenase (DYPD) were down-regulated in the metastatic tissues in comparison
      with the paired primary tissues, which was identified by both radioactivity
      labeled reverse dot blot hybridization and fluorescence-labeled gene microarray
      hybridization. KNSL4 mRNA expression had a down-regulation trend with increasing
      metastatic ability of breast cancer cell lines. CONCLUSIONS: The gene expression
      profiling of the lymph node metastasis is almost similar to that of their primary
      breast cancer, indicating that the metastatic cancer cells in lymph node are the
      subclone with higher metastasis ability of the primary cancer cells, and that
      some differentially expressed genes between them may be involved in the change of
      metastasis phenotype. KNSL4 and DYPD are potential metastasis-related genes, and
      KNSL4 mRNA expression is correlated with metastasis behaviors of the breast
      cancer cell lines, suggesting that KNSL4 may play an important role in the
      metastasis process of breast cancer.

PMID- 17199994
TI  - [Study on trans-differentiation of adult human myoblasts into neural precursor
      cells and its implantation in rats].
AB  - OBJECTIVE: To investigate the feasibility of inducing adult human myoblasts into
      neural precursor cells. METHODS: The myoblasts were isolated with mixed digestive
      enzyme from minced human temporal muscle samples, cultured and purified clonally.
      The 3rd passage cells were incubated with serum free medium including basic
      fibroblast growth factor (bFGF), epidermal growth factor (EGF) and leukemia
      inhibitory factor (LIF). Morphological change was investigated during incubation
      period. Immunofluorescence cytochemistry and RT-PCR analysis were used to assess
      cell differentiation and trans differentiation. RESULTS: After the induction,
      cells became non-adherent aggregates as neurospheres. The myoblast-derived
      neurospheres was immuno-positive for nestin. In differentiation condition, they
      looked like neurons and glial cells and expressed neuronal (microtubule
      associated protein 2, MAP-2), astrocytic (Glial fibrillary acidic protein, GFAP)
      and oligodendrocytic (Galactocerebroside, Galc) markers by immunocytochemistry.
      The result by RT-PCR was coincident with immunocytochemistry. The myoblast
      derived neurospheres expressed MAP-2 and GFAP after they were transplanted into
      the brain of rats with cerebral ischemia. CONCLUSION: Adult human myoblasts can
      be inducted to trans-differentiate into neural precursor cells.

PMID- 17199995
TI  - [Neutrophils induce the maturation and activation of immature dendritic cells
      during adaptive immune responses].
AB  - OBJECTIVE: To investigate whether polymorphonuclear neutrophilic leucocyte (PMN)
      can induce the maturation and activation of immature dendritic cells, thus
      promoting the Th1 immunity to microbial pathogens in vitro. METHODS: PMN isolated
      from mouse bone marrow were stimulated by lipopolysaccharide (LPS), and were
      cultured with immature DC (imDCs) isolated from mouse bone marrow for 18 hours.
      Then the analysis of DC surface markers CD40 and CD86 was done by flow cytometry,
      and ELISA was used to detect the levels of TNF-alpha and IL-12. Purified DC
      cocultured with LPS-PMN (PMN-DC) and imDC were incubated with fluorescein
      isothiocyanate conjugated OVA (FITC-OVA), and the phagocytic capacity of PMN-DC
      and imDC was assessed by flow cytometry. Splenic CD4(+) T cells from DO11.10 x
      C57BL/6 F1 hybrid mice were obtained, and then cultured with PMN-DC or imDC in
      the presence of OVA (323 - 339). The cells were double stained with anti-CD4-PE
      and 7-amino-actinomycin D. The cellular data were acquired for 56s with a flow
      cytometer and the assay of IFN-gamma and IL-4 was done by intracellular staining.
      RESULTS: LPS-PMN induced strong up-regulation of CD40 and CD86, and this capacity
      was remarkably inhibited after being neutralized by anti-TNF-alpha monoclonal
      antibody. LPS-PMN also stimulated imDCs to produce IL-12 and TNF-alpha. PMN-DCs
      demonstrated decreased phagocytic capacity compared with that of imDCs.
      Furthermore, the PMN-DC induced considerable DO11.10 T cell proliferation, and
      stimulated DO11.10 T cell to produce a large amount of IFN-gamma, but a
      relatively low amount of IL-4. CONCLUSION: LPS-PMN can induce the maturation and
      activation of imDCs, including the cytokine secretion, specific antigen
      presentation and Th1 differentiation, thus promoting the type I immunity to
      microbial pathogens.

PMID- 17199996
TI  - [Synthetic RGD-containing peptide K16GRGDSPC affected the adhesion, proliferation
      and osteogenic differentiation of rabbit bone marrow stromal cells on PLGA-[ASP
      PEG] scaffold materials].
AB  - OBJECTIVE: To explore the effects of synthetic RGD-containing peptide K16GRGDSPC
      covalent bonding with PLGA-[ASP-PEG] scaffold materials on the adhesion,
      proliferation and osteogenic differentiation of rabbit bone marrow stromal cells
      (BMSCs). METHODS: The peptide was synthesized by solid-phase synthesis method and
      characterized by mass spectrometry and high pressure liquid chromatography. PLGA
      [ASP-PEG] scaffold materials were modified with the peptide by cross linker Sulfo
      LC-SPDP and detected by XPS. The BMSCs obtained from rabbit were cultured on PLGA
      [ASP-PEG] modified with the peptide and those cultured on unmodified PLGA-[ASP
      PEG] were also observed as control group. The adhesion and proliferation
      behaviors of the cells were analyzed by conventional precipitation method,
      micropipette aspiration technique, MTT assay and Coomassie Brilliant Blue dyes.
      The osteogenic differentiation of the cells was showed by the activity of
      alkaline phosphatase (ALP) assayed by ALP Assay Kit and the mRNA levels of ALP,
      osteocalcin (OCN), osteopontin (OPN) and collagen I assessed by real-time PCR (RT
      PCR). Immunofluorescence stain was also used to detect the expression of core
      binding factor a1 (Cfba1) which was an osteogenic maker as well. RESULTS: The
      peptide was successfully manufactured and linked to the surface of the PLGA-[ASP
      PEG] by the cross-linker. The abilities of adhesion and proliferation and the
      expressions of osteogenic makers of the cells were significantly higher than
      those of control group (P < 0.05). CONCLUSION: RGD-containing peptide K16GRGDSPC
      could promote the adhesion, proliferation and osteogenic differentiation of BMSCs
      on the biomimetic bone-matrix materials.

PMID- 17199997
TI  - [Effects of beta-sitosterol on microtubular systems in cervical cancer cells].
AB  - OBJECTIVE: To investigate beta-sitosterol's inhibitory effects on SiHa cells'
      growth, and the effects on microtubular system in SiHa cell. METHODS:
      Proliferation inhibition of SiHa cell line was evaluated by MTT assay. Cell cycle
      of SiHa cells treated with beta-sitosterol was analyzed by flow cytometry. The
      expression and distribution of microtubule and microtubule associated protein 2
      in SiHa cells were investigated by confocal microscopy. Immunoblotting analysis
      was used to determine tubulin alpha, microtubule associated protein 2, and the
      proportion of polymerization of tubulin. RESULTS: beta-sitosterol could obviously
      inhibit the proliferation of SiHa cells, and induce the accumulation of cells in
      S phase (rather than the G2/M phase) and mitotic arrest in the cell cycle.
      Confocal microscopy showed an abnormal microtubular network in SiHa cell treated
      with beta-sitosterol for 5 days, and the expression of microtubule associated
      protein 2 was marked down-regulated. Further analysis by immunoblotting confirmed
      the down-regulation of beta-sitosterol on the expression for both microtubule
      associated protein 2 and tubulin alpha. Moreover, beta-sitosterol reduced the
      proportion of polymerization of microtubule in a time-dependent manner.
      CONCLUSION: beta-sitosterol could down-regulate the expression of tubulin alpha
      and microtubule associated protein 2 in SiHa cells, and inhibit the microtubular
      polymerization. Our results suggested an anti-microtubule characteristic of beta
      sitosterol which might contribute to the proliferation inhibition of SiHa cells.

PMID- 17199999
TI  - [An improved operation approach for bipedal rat model construction].
AB  - OBJECTIVE: To explore an improved operation approach to make up the ethical
      deficiency of classical bipedal rat model. METHODS: 20 SD rats were randomly
      divided into an improved group and a traditional group averagely. Improved group
      were operated with plexus brachialis nerve amputation, while traditional group
      with forelimbs amputation close to shoulder joint. Forelimb and shoulder joint
      movements were observed and electromyography of the peripheral muscles around
      shoulder joint were recorded to make certain the paralytic scope. Operation
      duration and axillary artery hurt probability of both the improved and
      traditional operation were compared to evaluate the operation risk of improved
      approach. Mean total upright time on 2 d, 1 w, 2 w, 4 w and 6 w post-operation
      and upright posture on 6 w post-operation were recorded to evaluate the human
      upright-posture-simulating effect of bipedal rats operated with improved
      approach. RESULTS: Compared with classical amputation approach, improved approach
      exhibited simpler operation procedure, shorter operation duration and lower
      axillary artery hurt probability. Electromyography revealed that all forelimb
      muscles and most shoulder-peripheral muscles were denervated, forelimbs of the
      improved bipedal rats were absolutely paralyzed and shoulder joint reserved only
      slight abduction function. The mean total upright time of improved bipedal rats
      was longer than the classical ones after 2 w post-operation, while upright
      posture showed no difference with classical bipedal rats. CONCLUSIONS: The
      improved operation approach not only simplified operation procedures, but also
      achieved even better effect than classical amputation operation and exempted
      bipedal rat model from the ethical shadow.

PMID- 17199998
TI  - [An experimental study of recombinant human erythropoietin on the treatment of
      acute myocardial infarction in rats].
AB  - OBJECTIVE: To observe the treatment and it's mechanisms of rHu-EPO on acute
      myocardial infarction of SD rats in vitro and vivo. METHODS: Cardiomyocytes were
      isolated from neonatal Sprague-Dawley rats. Hypoxia condition and oxidative
      stress were used to induce apoptosis. rHu-EPO was added to the culture system.
      Apoptosis was assessed by using Hoechst 33258 dyeing. Apoptosis index (AI) was
      then calculated. Thirty two rats were divided into three groups including sham
      operation group (Sham), acute myocardial infarction group (MI) and treated group
      (MI + EPO). Acute myocardial infarction model was made by ligating the anterior
      descending coronary artery. rHu-EPO was administered i.p. in MI + EPO group at
      the dose of 5000 units/kg of body weight immediately after the ligation and the
      next six days. At the fourteenth day all animals underwent hemodynamic
      measurements and then executed, the samples were examined with hematoxylin and
      eosin (HE) stain, immunohistochemistry technique (Bcl-2, Bax) and TdT-mediated
      dUTP nick end labeling (TUNEL) dyeing. RESULTS: rHu-EPO significantly down
      regulated the apoptosis of cardiomyocytes which underwent hypoxia or oxidative
      stress. In vivo experiment rHu-EPO protected the hemodynamic function of the rats
      from myocardial infarction and down-regulated the ratio of the positive cells for
      TUNEL and Bax. The ratio of the positive cells for Bcl-2 was up-regulated by rHu
      EPO. CONCLUSION: These findings suggested rHu-EPO improve myocardial infarction
      by attenuating apoptosis. Potential mechanism is to up-regulated Bcl-2 expression
      and down-regulated Bax expression.

PMID- 17200011
TI  - [Standardization of the pancreaticoduodenectomy operation to pancreatic head
      cancer].

PMID- 17200012
TI  - [The role of human fibroblast growth factor receptor 1-IIIb isoform in
      proliferation of pancreatic ductal cells and its effects to mitogen-activated
      protein kinase].
AB  - OBJECTIVE: To study the role of IIIb isoform of human fibroblast growth factor
      receptor 1 (FGFR1-IIIb) in proliferation of pancreatic ductal cells and its
      effects on mitogen-activated protein kinase (MAPK). METHODS: Human pancreatic
      ductal cells of the line TAKA-1 were cultured. The plasmid of human full-length
      FGFR1-IIIb isoform, pSVK4/FGFR1-IIIb, was stable transfected into the cultured
      TAKA-1 pancreatic ductal cells facilitated by lipofectamine. Un-transfected TAKA
      1 cells and TAKA-1 ductal cells transfected with blank plasmid were used as
      controls. The expression, distribution and character of protein of FGFR1-IIIb in
      the TAKA-1 cells were estimated by Western blotting, Northern blotting,
      immunofluorescence assay, and glycosylation assay. The function and mechanism of
      FGFR1-IIIb in the transfected pancreatic ductal cells stimulated by FGF were
      examined by MTT assay and MAPK assay. Tunicamycin, an inhibitor of N-terminal
      glycoprotein synthesis, was added into the culture fluid of the FGFR1-IIIb
      transfected TAKA-1 cells to observe the changes of the FGFR1 bands. RESULTS:
      FGFR1-IIIb, a glycosylated receptor at various levels at 120 kDa and between 130 
      150 kDa, was localized at moderate levels at the cell membrane and cytoplasm and
      at higher level in the perinuclear region of the cytoplasm of the pSVK4/FGFR1
      IIIb-transfected cells. FGF-1, -2, and -4 significantly increased the growth of
      FGFR1-IIIb-transfected TAKA-1 cells, and at the same time induced the p44/p42
      MAPK phosphorylation. CONCLUSION: Human FGFR1-IIIb receptor is a functional
      receptor in pancreatic ductal cells. FGF-1, -2, and -4 can increase the growth of
      FGFR1-IIIb-transfected pancreatic ductal cells, and the mechanism is that they
      can induce the p44/p42 MAPK phosphorylation.

PMID- 17200013
TI  - [Expression of S100A2 in secondarily radioresistant pancreatic cancer cells and
      significance thereof].
AB  - OBJECTIVE: To investigate the association of S100A2 expression with the secondary
      radioresistance in pancreatic cancer cells. METHODS: Human pancreatic cancer
      cells of the line SW1990, parental line, and the secondarily radioresistant human
      pancreatic cancer cells of the line SW1990/R were cultured and inoculated into
      the wells of a 6-well plate. 5-Aza-2'-deoxycytidine (5-aza-DC) of different
      concentrations was added into the culture fluid. Forty-eight hours later X-ray
      irradiation was conducted. Cloning efficiency assay was used to assess the cell
      survival. The cell cycle was analyzed by flow cytometry. The mRNA expression of
      S100A2 was examined by real-time RT-PCR and the protein expression of S100A2 was
      examined by immunofluorescence quantitative analysis. RESULTS: The S100A2 mRNA
      expression level of the SW1990 line was significantly higher than that of the
      SW1990/R line. Treated by 5-aza-dC, the S100A2 mRNA expression level of the
      SW1990/R line increased by 2 approximately 3 times. The S100A2 protein expression
      level of the SW1990 line was significantly higher than that of the SW1990/R line
      (t = 3.648, P = 0.022). Treated by 5-aza-dC, the S100A2 protein expression level
      of the SW1990/R line increased, by 5 times at most (t = -11.404, P = 0.001). The
      G(2)/M of the SW1990 line was 16.2%, significantly higher than that of the
      SW1990/R line (16.2%), and the G(2)/M levels of the SW1990/R line treated by 5
      aza-dC of different concentrations were all increased dose-dependently. The
      colony-forming rates of the SW1990/R line of the 5-aza-dC + irradiation groups
      were all significantly lower than that of the SW1990/R line of the pure
      irradiation group, even the dose of 5-aza-dC was as low as 0.025 microm. The SF2
      (cell survival rate with the irradiation dose of 2 Gy) of the 5-aza-dC +
      irradiation group was 0.122, significantly lower than that of the pure
      irradiation group (0.460). CONCLUSION: The expression level of S100A2 is low in
      the radioresistant pancreatic cancer cells, which may be one of the mechanisms of
      radioresistance of these cells.

PMID- 17200014
TI  - [Expression of Snail and E-cadherin in pancreatic carcinoma and clinical
      significance thereof].
AB  - OBJECTIVE: To investigate the expression of Snail, a newly discovered inhibitory
      transcription factor, and E-cadherin in pancreatic carcinoma (PC) and clinical
      significance thereof. METHODS: Immunohistochemistry was used to examine the
      expression of Snail and E-cadherin in 56 specimens of PC obtained during
      operation. PC cells of the line of Panc-1 and transfected with pCMV-Tag2B-Snail,
      a eucaryotic expression vector coding Snail, so as to obtain a stable clone named
      Panc-1-Snail. RT-PCR was used to detect the mRNA expression of Snail gene in the
      Panc-1-Snail cells. Immunofluorescence technique and Western blotting were used
      to detect the expression of E-cadherin in the Pan-1-Snail cells. Transwell cell
      culture chamber method was used to examine the invasion ability of the Panc-1-and
      Panc-1-Snail cells. RESULTS: Twenty of the 56 PC specimens (36%) were positive in
      Snail, mainly located in the nuclei. Seventeen of the 20 Snail-positive PC
      specimens were with and 3 without lymph node metastasis (P = 0.006); and 7 of the
      8 PC specimens with lymph node metastasis were Snail-positive and only 1 was
      Snail-negative (P = 0.001). Twenty-six PC specimens showed low expression of E
      cadherin with remarkable heterogeneity. Of the 20 Snail-positive PC specimens 13
      showed low expression of E-cadherin and only 7 showed normal expression of E
      cadherin; and 13 of the 36 Snail-negative PC specimens showed low expression of E
      cadherin (P = 0.038). RT-PCR showed strong Snail mRNA expression in the Pan-1
      cells. Both Western blotting and immunofluorescence technique showed the
      depression of E-cadherin expression. The Transwell chamber test showed that the
      number of penetrating Pan-1-Snail cells after 24-hour incubation was (174 +/-
      8)/200X field of view, significantly greater than that of the Pan-1 cells [(96 +/
      4)/200X field of view, P < 0.01]. CONCLUSION: Re-expressed in PC and
      accelerating the invasion of PC through depressing E-cadherin expression, Snail
      may present a new marker for predicting the aggressiveness of PC.

PMID- 17200016
TI  - [Dynamic monitoring of serum pepsinogen among high risk populations of gastric
      cancer in Zhuanghe county].
AB  - OBJECTIVE: To investigate the dynamic changes of serum pepsinogen (PG) among the
      high risk populations of gastric cancer. METHODS: Peripheral blood samples were
      collected from 444 subjects in the high risk areas of gastric cancer in Zhuanghe
      county, Liaoning province, who underwent screening of gastric cancer, 225 males
      and 219 females, aged 48.31 (21 - 76). ELISA was used to measure the serum PG I
      and PG II. The PG I/II ratio was calculated. Gastroscopy was conducted to take 4
      pieces of biopsy specimens from each subject to undergo pathological examination.
      Histological examination and serum Hp-IgG antibody determination by ELISA were
      performed to detect the infection of Helicobacter pylori (Hp). The above
      mentioned examinations were carried out at the first screening and 6, 12, and 30
      months later during follow-up. RESULTS: (1) In the age group 51 - 60, the
      percentage change in PG II of 6-month follow-up was 0.84, significantly lower
      than those of the 12-month follow-up (1.22, P = 0.019) and 30-month follow-up
      (1.24, P = 0.004), and the percentage change in PG I/II of the 6-month follow-up
      was 1.09, significantly higher than those of the 12-month follow-up (0.75, P =
      0.027) and 30-month follow-up (0.69, P = 0.001). However, there were no
      significant differences in serum PG I, serum PG II, and PG I/II ratio in other
      age groups. (2) The percentage change in serum PG I of the patients of
      superficial gastritis (SG) with mitigation of the 6-month follow-up was 0.69,
      significantly lower than that of the 12-month follow-up (0.97, P = 0.002). The
      percentage change in PG I/II of the patients of atrophic gastritis (AG) with
      mitigation of the 6-month follow-up was 1.13, significantly higher than that of
      the 12-month follow-up (0.75, P = 0.042). (3) The percentage change in PG I of
      the SG-->NOR (normal) group was 0.94, significantly higher than that of the SG-
      >AG group (0.79, P = 0.002). The percentage changes in PG I and PG II of the AG-
      >NOR group were 0.43 and 0.60 respectively, both significantly lower than those
      of the AG-->SG group (0.87, P = 0.000, and 1.11, P = 0.010). (4) The percentage
      change in PG I of the Hp negative-->Hp positive group was 0.94, significantly
      higher than that of the Hp negative-->Hp negative group (0.81, P = 0.026). The
      percentage changes in PG I and PG II of the Hp positive-->Hp negative group were
      0.74 and 0.86 respectively, both significantly lower than those of Hp positive-
      >Hp positive group (0.93 and 1.15 respectively, both P = 0.000), and the
      percentage change in PG I/II of the Hp positive-->Hp negative group was 0.90,
      significantly higher than that of the Hp positive-->Hp positive group (0.70, P =
      0.022). CONCLUSION: The percentage change of serum PG is correlated with time of
      follow-up, feature of stomach disease, and status of Hp infection. Dynamic
      detection of serum PG can be applied in monitoring the populations in high risk
      area of gastric cancer.

PMID- 17200018
TI  - [Transfecting rat heart with human pacemaker gene in vivo to create a biological
      pacemaker].
AB  - OBJECTIVE: To test the ability and safety of injecting the hHCN gene into the
      ventricle of intact rats to create a novel biological pacemaker and to explore
      the duration of the hHCN over-expression in vivo. METHODS: Adenoviral constructs
      incorporating hHCN4 and green fluorescent protein (GFP) were subepicardially
      injected into the rats' left ventricular wall in situ (n = 10). Control group was
      injected with adenoviral constructs of GFP alone (n = 10). ECGs were recorded
      every day within the initial three days after operation. Up to seven days after
      injection, all rats were anesthetized and subjected to cervical vagal trunks
      stimulation to permit the emergence of escape rhythm. Then pace-mapping was
      performed by the hand-hold electrode. Finally, hearts were removed for histology
      and immunofluorescence study. RESULTS: Ventricular arrhythmic events were not
      found during the first three days. During vagal stimulation, the rate of
      spontaneous rhythm in the hHCN4-injected group was significantly more rapid than
      that in the control group (69 bpm +/- 6 bpm vs 41 bpm +/- 10 bpm, P < 0.001).
      Pace-mapping confirmed the escape rhythm in the hHCN4-injected group was
      originated near the injection site. Immunofluorescence study showed the
      overexpression of hHCN4 on the site of injection. However, the duration of hHCN
      overexpression was no more than one month after injection. CONCLUSION: The
      overexpression of hHCN4 provides ventricular escape rhythm with the
      physiologically acceptable rate. Long-term feasibility of this approach needs to
      be tested.

PMID- 17200020
TI  - [The efficacy of early intervention for infants and toddlers with hearing loss].
AB  - OBJECTIVE: To investigate the efficacy of early intervention on language,
      pronunciation and cognitive developments of infants and toddlers with hearing
      loss and to build up an early intervention model. METHODS: Fifty-six children
      with moderate to profound sensorineural hearing loss aged 10 months to 2 years
      were divided into two groups. 20 children, aged 10 months to 2 years, received
      early intervention services after wearing hearing aids for 6 - 18 months, and 36
      children, aged 11 months to 2 years, didn't receive any intervention. The type
      and degree of hearing loss were measured by a series of auditory tests. Language
      and cognitive developments of the children with hearing loss and 28 age, and sex
      matched children with normal hearing, aged 10 to 23 months, were evaluated by the
      Gesell developmental schedules. The results were expressed as developmental
      quotient (DQ). Pronunciation test in mandarin Chinese was adopted to evaluate the
      speech development of the 56 children with hearing loss. RESULTS: (1) The
      language DQ according the Gesell developmental schedules of the children with
      hearing loss who received early intervention was (92.25 +/- 17.32), significantly
      higher than those children with hearing loss who didn't receive intervention
      (70.44 +/- 29.99, P = 0.00), whish was significantly lower than that of the
      normal hearing children (P = 0.00). However, there was no significant difference
      in language DQ between the children who received early intervention and the
      normal hearing children. There was no significant correlation between the degree
      of hearing loss and language DQ in the children who received early intervention
      (P = 0.27). (2) The personal-social developmental quotient (DQ) of the children
      who received intervention was (101.40 +/- 7.66), significantly higher than that
      of the children who didn't receive intervention (83.94 +/- 22.09, P = 0.00), that
      were significantly lower than that of the children with normal hearing (P =
      0.00). However, there were no significant difference in the personal-social DQ
      between the children who received early intervention and the children with normal
      hearing. No significant differences in the gross motor ability, fine motor
      ability and adaptive ability were observed between the two groups of children
      with hearing loss and normal hearing children. (3) The consonant pronunciation of
      the children with moderate to severe hearing loss who received early intervention
      was normal. Among those children only one case with profound hearing loss
      had/d/error. The consonant pronunciation of the children with moderate hearing
      loss who didn't receive early intervention of those was normal. One case with
      moderate-severe hearing loss and one case with severe hearing loss had/d/errors.
      Six cases with profound hearing loss had/d, m/errors. The tone of the children
      with moderate to severe hearing loss who received early intervention was normal.
      Three cases with profound hearing loss exhibited tone errors. Among the children
      who didn't receive early intervention, tone errors were found in two cases with
      moderate hearing loss, one case with moderate-severe hearing loss, one case with
      severe hearing loss, and twelve cases with profound hearing loss showed.
      CONCLUSION: The language, pronunciation and cognitive developments of the
      children who don't receive early intervention are significantly lower than those
      of the children with normal hearing. Early intervention can significantly improve
      the language, speech and cognitive abilities of children with hearing loss.

PMID- 17200021
TI  - [Transduction efficacy of recombinant type 1 and type 2 adeno-associated virus in
      the retinal cells].
AB  - OBJECTIVE: To investigate the transduction and gene expression of the recombinant
      adeno-associated viruses (rAAV) of the serotypes 1 and 2 in the retinal cells.
      METHODS: rAAV vectors of type 1 and type 2 encoding EGFP were infected into the
      cultured retinal pigmentary epithelium (RPE) cells of the line CRL-2302 and
      primarily cultured retinal neural cells from normal SD rats, and primarily
      cultured RPE cells from an adult cornea donor. The cultured RPE cells transduced
      by rAAV2-EGFP or rAAV2/1-EGFP were harvested at the 7 th and 14 th day after
      infection to be detected by fluorescence-activated cell sorter. The onset of EGFP
      gene expression and EGFP positive rate were detected by flow cytometry and
      fluorescence microscopy. Then, rAAV2/1-EGFP and rAAV2-EGFP were injected into the
      subretinal spaces of 32 SD rats to investigate the onset of EGFP fluorescence and
      its distribution in the fundus in vivo via fluorescence stereoscope. HE staining
      and immunohistochemistry were used to observe the infected cell type and immune
      response in the retina. RESULTS: The percentage of EGFP positive cells and mean
      intensity of EGFP fluorescence in the cells transduced by rAAV2-EGFP 7 and 14
      days after transduction were 13.50% +/- 1.70% and 15.60% +/- 0.82%, and 2.75 +/-
      0.12 and 3.80 +/- 0.72 respectively; and the EGFP positive cells and mean
      intensity of EGFP fluorescence in the cells transduced by rAAV2/1-EGFP were 1.09%
      +/- 0.5% and 1.98% +/- 0.45%, and 1.12 +/- 0.09 and 1.75 +/- 0.2 respectively.
      The EGFP fluorescence area in the retina were (5389 +/- 211) microm(2), (9832 +/-
      364) microm(2), (14 454 +/- 446) microm(2), (20 528 +/- 648) microm(2), and (20
      264 +/- 683) microm(2) respectively 3, 7, 14, and 75 days, and 4 month after
      transduction by rAAV2-EGFP in vivo; In the rat retina transduced by rAAV2/1-EGFP,
      the EGFP fluorescence areas were (9666 +/- 348) microm(2), (12 160 +/- 439)
      microm(2), (19 794 +/- 621) microm(2), (26 172 +/- 923) microm(2), and (26 022 +/
      965) microm(2) respectively 3, 7, 14, and 75 days, and 4 month after infection.
      CONCLUSION: rAAV2 efficiently transduces retinal cells both in vitro and in vivo.
      rAAV2/1 is a more effective gene-transferring vector to be used in retinal cells
      in vivo than rAAV2.

PMID- 17200023
TI  - [Development of a DNA chip screening mitochondrial DNA mutations in patients with
      diabetes mellitus].
AB  - OBJECTIVE: To establish a rapid and precise high-throughput mitochondrial (mt)
      DNA chip and to investigate the relationship between mtDNA tRNA Leu (UUR) and ND1
      gene mutations and diabetes mellitus. METHODS: A wild-type and mutant probes of
      28 loci in tRNA Leu (UUR) and ND1 gene were immobilized on the Hybond N + nylon
      membrane by UV-crosslinking, then the mtDNA chips were used to detect 28 loci
      mutation in 200 cases of type 2 diabetes mellitus and 210 matched healthy
      controls. All the mutations were further confirmed by DNA sequencing. Mfold and
      Antherprot softwares were used to predict the secondary structures of the mutant
      gene and protein. RESULTS: The mtDNA chip, which could detect 28 loci mutations,
      was successfully developed. In diabetic group, there were 2 (1.0%) cases of T3
      290C mutation, 6 (3.0%) of G3 316A (Ala-->Thr) mutation, 5 (2.5%) of T 3 394C
      (Tyr-->His) mutation, 1 (0.5%) of T3 593 C (Val-->Ala) mutation, 1 (0.5%) of A3
      606G (Leu-->Leu) mutation, 8 (4.0%) of A4 164G (Met-->Met) mutation, 2 (1.0%) of
      T4 216C (Met-->His) mutation. In the controls, 1 (0.5%) carrier of G3 316A
      mutation and 5 (2.4%) carriers of A4 164G mutation were found. There was
      significant difference between two groups for T3 394C mutation frequencies (P =
      0.027). The secondary structures of the mutant proteins of G3 316A, T3 394C, T3
      593C and T4 216C mutations were all different from those of the wild-types'.
      CONCLUSION: mtDNA chip is a rapid and reliable high-throughput method for
      mutations detection, and T3 394C mutation in ND1 gene might contribute to the
      pathogenesis of mitochondrial diabetes.

PMID- 17200022
TI  - [Effects of gene therapy with replication-defective adenovirus ericlosing Egr-1
      promoter and Smad7 cDNA on irradiation-induced pulmonary fibrosis: experiment
      with mice].
AB  - OBJECTIVE: To investigate the effects of gene therapy with replication-defective
      adenovirus enclosing Egr-1 promoter and Smad7 cDNA on irradiation-induced
      pulmonary fibrosis. METHODS: The recombinant replication-defective adenovirus AD.
      Egr-Smad7 enclosing Egr-1 promoter and Smad7 cDNA was constructed. 288 C57BL mice
      were randomly divided into 6 groups: AD. Egr-Smad7 group (Group RA, receiving
      intratracheal instillation of AD. Egr-Smad7 of the dose of 10(9) pfu/0.1 ml), AD.
      Egr-Smad7 + radiation group (Group RAR, receiving intratracheal instillation of
      AD. Egr-Smad7 of the dose of 10(9) pfu/0.1 ml and then radiation to the chest 14
      h later), replication-defective adenovirus group (Group AV, receiving
      intratracheal instillation of replication-defective adenovirus of the dose of
      10(9) pfu/0.1 ml), replication-defective adenovirus + irradiation group (Group
      AVR, receiving intratracheal instillation of replication-defective adenovirus of
      the dose of 10(9) pfu/0.1 ml and then radiation to the chest 14 h later), blank
      control group (Group C), and pure irradiation group (Group R), each group was re
      divided into 6 subgroups of 8 mice to be observed 0, 1, 2, 4, 8, and 12 weeks
      after the treatment. The mice were killed at different time points and their
      lungs were taken out. The levels of type I collagen, type III collagen,
      connective tissue growth factor (CTGF), and transforming growth factor-beta1 (TGF
      beta1) were detected by ELISA. The level of hydroxyproline was examined by
      alkaline hydrolysis method. The lung tissues were stained with HE to undergo
      pathological examination. RESULTS: The TGF-beta1 levels of the irradiation groups
      all increased, peaking in the second week (all P < 0.05), all significantly
      higher than those of Group C. However, the TGF-beta1 levels at different time
      points of Group RAR were all significantly lower then those of the other
      irradiation groups. The CTGF levels of different groups at different time points
      were all significantly higher than those of Group C (P < 0.05 or P < 0.01), and
      the CTGF levels of Groups RA and AV were decreased to almost normal 12 weeks
      after the irradiation. The levels of type I collagen and type III collagen of the
      1 and 2-week subgroups of Group RAR were significantly lower than those of Group
      C (all P < 0.01), then gradually increased, and were slightly higher than those
      Group C 12 weeks later. The levels of type I collagen and type III collagen at
      different time points of the other groups were all significantly higher than
      those of Group C (P < 0.05 or P < 0.01). However, The levels of type I collagen
      at different time points of Group RAR were all lower than those of the other
      groups except Group C, and the levels of type III collagen in the first to eighth
      weeks after irradiation of Group RAR were all lower than those of the other
      groups except Group C. The hydroxyproline level of the 1 and 2 week subgroups of
      Group RAR were significantly lower than those of Group C (all P < 0.01), and then
      gradually increased. The hydroxyproline levels of the other irradiation groups
      all gradually increased significantly, peaking at the 12 th week (all P < 0.01).
      1 approximately 2 weeks after irradiation Groups RAR, RA, and AV showed
      remarkable pulmonary congestion changes, even more remarkable then those in Group
      R, 8 approximately 12 week later, fibrosis changes were found in Group R and AVR,
      and 12 weeks later the histological structure of lung of Group AV, RAR, and RA
      returned almost normal. CONCLUSION: Radioactive rays induce Egr-1 promoter to
      regulated the expression of exogenous Smad7 gene that blocks the signal
      transduction of TGF-beta. Thus use of AD. Egr-Smad7 may become a novel strategy
      of gene therapy in prevention and treatment of pulmonary fibrosis.

PMID- 17200024
TI  - [Multi-slice computed tomography of myocardial bridge and mural coronary artery
      and clinical significance thereof].
AB  - OBJECTIVE: To investigate the diagnosis of myocardial bridge and mural coronary
      artery (MB-MCA) with multi-slice computed tomography (MSCT) and clinical
      significance thereof. METHODS: 900 patients suspected as with coronary artery
      disease (CHD) underwent 64-slice computed tomography performed by 3 radiologists
      independently. When consistency was obtained among the independent
      interpretations of the tomogram among them the diagnosis of MB-MCA could be
      confirmed. The length of MCA and thickness of MB were measured, and the situation
      of the nearby arteries were observed and recorded. Based on the above mentioned 3
      items the reference scoring criteria were established. RESULTS: 180 sites of MB
      NCA were found in 167 (18.56%) of the 900 patients, 112 males and 55 females,
      aged 54.46 (33 - 84). 167 of the 180 sites of MB-MCA were located on the LAD
      (92.7%). MCA could be covered by MB in a form of semi-circularity (63.89%,
      115/180) or circularity (36.11%, 65/180) The length of MCA was 18.7 mm +/- 10.2
      mm, and the thickness of MB was 1.7 mm +/- 1.2 mm. 70% of the arteries proximal
      and/or distal to the MB-MCA were tortuous. Length of MCA < 10 mm, half
      surrounding of MB, and smoothness of the proximal and distant vessels were scored
      as 1; length of MCA of 10 approximately 20 mm, thickness of MB < 1 mm, and
      tortuousness of the unilateral proximal or distant vessel were scored as 2; and
      length of MCA > 20 mm, thickness of MB > 1 mm, and tortuousness of the bilateral
      proximal and distant vessels were scored as 3. Coronary atherosclerosis was found
      in 88 of the 167 patients (52.69%). No significant correlation was found between
      coronary atherosclerosis and MB-MCA grade (u = 1.234, P > 0.05). CONCLUSION:
      Sixty-four-slice CT can be used to confirm the presence of MB = MCA and the
      morphology of coronary artery with MB-MCA. Coronary atherosclerosis is not
      significantly correlated with MB-MCA grade.

PMID- 17200025
TI  - [Quantitative method to describe the inner characteristics of hereditary
      nonpolyposis colorectal cancer family].
AB  - OBJECTIVE: To establish a quantitative method to describe the inner
      characteristics of hereditary nonpolyposis colorectal cancer (HNPCC) family.
      METHODS: All members of 25 HNPCC families with assembly of malignant tumors
      therein [with at least one patients with colorectal cancer (CRC)] in China
      underwent questionnaire survey. Other 32 HNPCC families with complete clinical
      data were collected from the published Chinese and foreign literatures related to
      clinical phenotype of Chinese HNPCC family. Altogether 57 HNPCC families
      fulfilling the Amsterdam Criteria (AC) I or II underwent analysis of the inner
      characteristics cumulatively. The following parameters were analyzed: familial
      median age when diagnosed as with the first malignant tumor (FMA-DFMT), familial
      median age when diagnosed as with the first CRC (FMA-DFCRC), familial proportion
      of CRC in first malignant tumors (FPCRC-FMT), familial proportion of CRC patients
      (FP-CRCP), number of involved generations, number of cancer patients, and type of
      family. RESULTS: In the ACI HNPCC families, the distribution patterns of both FMA
      DFMT and FMA-DFCRC were not normal distribution. Most of the FMA-DFMT and FMA
      DFCRC were from 35 years to 50 years with the medians of 44.0 years and 43.5
      years respectively. The FPCRC-FMT and FP-CRCP were less than 0.6 in 13.2% (7/53)
      and 7.5% (4/53) of the families respectively. The FMA-DFMT and FMA-DFCRC were not
      correlated with FPCRC-FMT, FP-CRCP, number of involved generations and cancer
      patients, and type of family (all P > 0.05). CONCLUSION: Compared to the
      traditional methods, the features of HNPCC families can be accurately described
      by a series of quantitative parameters.

PMID- 17200026
TI  - [Non-steroidal anti-inflammatory drug induced gastropathy and preventive effects
      of teprenone on the gastropathy in rats].
AB  - OBJECTIVE: To construct the model of non-steroidal anti-inflammatory drug (NSAID)
      induced gastropathy and observe the preventive effects of Teprenone on it in
      rats. METHODS: Ninety-one male Sprague-Dawley (SD) rats were divided into normal
      saline group, model group (I) and prophylaxis group (II). Group I includes four
      subgroups (Ia, Ib, Ic, Id) treated by indomethacin (5 mgxkg(-1)xd(-1)),
      combination of indomethacin (5 mgxkg(-1)xd(-1)) and prednisone (10 mgxkg(-1)xd(
      1)), celecoxib (100 mgxkg(-1)xd(-1)) and combination of celecoxib (100 mgxkg(
      1)xd(-1)) and prednisone (10 mgxkg(-1)xd(-1)) respectively. Group II also
      includes four subgroups (IIa, IIb, IIc, IId) pretreated by teprenone (12 mgxkg(
      1)xd(-1)) compared with group I. Lesion index (LI), pathohistology index,
      cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mRNA detected by RT-PCR
      were observed after 4 days. RESULTS: Compared with normal saline group, LI (11.00
      (1.00 - 22.5), 8.50 (0.75 - 14.50), 11.00 (3.50 - 14.75), P < 0.01) of three
      model subgroups (Ia, Ib, Id), and pathohistology indexes (1.00 (0.00 - 1.25),
      2.00 (0.00 - 5.00), 1.00 (0.00 - 3.00), 2.00 (0.00 - 2.00), P < 0.01) of the
      whole model group increased significantly (P < 0.05). Compared with corresponding
      model subgroups, LIs (0.00 (0.00 - 0.25), 1.00 (0.00 - 1.50), 0.00 (0.00 - 0.00),
      0.00 (0.00 - 1.00), P < 0.05) and pathohistology indexes (0.00 (0.00 - 0.00),
      0.00 (0.00 - 0.50), 0.00 (0.00 - 0.25), 0.00 (0.00 - 0.50), P < 0.05) of
      prophylaxis subgroups were decreased significantly (P < 0.05). There was obvious
      difference in LI between Ic and Ia as well as between Ic and Id (P < 0.05).
      Compared with normal saline group, COX-1 mRNA expression of the groups (Ia, Ib,
      Id, IIa, IIb and IId) increased (0.384 +/- 0.031, 0.354 +/- 0.026, 0.753 +/-
      0.049, 0.366 +/- 0.035, 0.381 +/- 0.036, 0.766 +/- 0.401, P < 0.001) while COX-2
      mRNA expression of the above groups decreased statistically (0.483 +/- 0.056,
      0.448 +/- 0.046, 0.461 +/- 0.050, 0.479 +/- 0.032, P < 0.001). CONCLUSIONS: These
      results suggested gastric mucosa lesions could be resulted from COX-2 inhibitors
      but better than those induced by traditional NSAID. Prednisone could promote the
      risk in NSAID induced gastropathy. In addition to COX-1 inhibition, other factors
      might also involved in NSAID induced gastropathy. Teprenone could prevented from
      NSAID induced gastropathy but the actions might be not associated with COXs.

PMID- 17200031
TI  - Impact of maternal nutrition and metabolism on health of the offspring.
AB  - Since the original publication of the theory of the fetal origins of adult
      diseases more than 15 years ago, extensive epidemiological studies have linked
      the environment in utero to adult health. Maternal nutrition and metabolism are
      major mechanisms by which the intrauterine environment programs the health of the
      offspring. Both growth-restricted and overgrown fetuses are at risk for postnatal
      disease. This paper summarizes the nutritional and metabolic causes of both these
      conditions and also reviews the interventions that have been tested to mitigate
      these effects.

PMID- 17200030
TI  - In vivo humoral and cellular reactions, and fate of injected bacteria Aeromonas
      hydrophila in freshwater prawn Macrobrachium rosenbergii.
AB  - Live non-opsonized and opsonized Aeromonas hydrophila were injected into
      juveniles of freshwater prawn Macrobrachium rosenbergii to study the cells
      involved in phagocytosis, distribution of bacteria, cellular reactions and
      clearance of both forms of bacteria from the system. The bacteria were rapidly
      distributed to various tissues viz., gills, heart, hepatopancreas within 1h, and
      the tissues revealed haemocytic nodule formation after 3 h of injection. There
      was rapid clearance of both the forms of bacteria from the circulation. However,
      clearance efficiency was significantly (P < 0.05) faster in the case of opsonized
      bacteria at 12 h after injection. Similarly, the nodule formation, that was
      prominent in cardiac musculature, was rapidly eliminated from the tissues of the
      group injected with opsonized bacteria as compared to non-opsonized bacteria
      injected group, thus confirming the existence of opsonic factors in haemolymph of
      this prawn. In another experiment, various dose levels of bacteria were injected
      intramuscularly into prawns and haemolymph was collected after 1, 6, 24, 72 h and
      7 days of injection to study various immune parameters. Although, no major
      alterations in the total and differential haemocyte counts were observed in
      bacteria injected prawns compared to control, there was a significant decline in
      phenoloxidase activity in the highest dose bacteria injected group at the earlier
      phase and a rise in agglutinin levels at the later phase of the experimental
      period in the higher dose groups.

PMID- 17200034
TI  - Re: Doping in the recombinant era.

PMID- 17200037
TI  - Management of chronic kidney disease-mineral bone disorder.

PMID- 17200038
TI  - Chronic kidney disease-mineral-bone disorder: a new paradigm.
AB  - Disturbances in mineral and bone metabolism are prevalent in chronic kidney
      disease (CKD) and an important cause of morbidity, decreased quality of life, and
      extraskeletal calcification that have been associated with increased
      cardiovascular mortality. These disturbances have traditionally been termed renal
      osteodystrophy and classified on the basis of bone biopsy. Kidney Disease:
      Improving Global Outcomes (KDIGO) recently sponsored a Controversies Conference
      to evaluate this definition. The recommendations were that (1) the term renal
      osteodystrophy be used exclusively to define alterations in bone morphology
      associated with CKD and (2) the term CKD-mineral and bone disorder (CKD-MBD) be
      used to describe the broader clinical syndrome that develops as a systemic
      disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is manifested
      by an abnormality of any one or a combination of the following: laboratory
      abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism; bone-changes
      in bone turnover, mineralization, volume, linear growth, or strength; and
      calcification-vascular or other soft-tissue calcification. The pathogenesis and
      clinical manifestations of these components of CKD-MBD are described in detail in
      this issue of Advances in Chronic Kidney Disease.

PMID- 17200039
TI  - Mineral metabolism and mortality in patients with chronic kidney disease.
AB  - Chronic kidney disease is associated with profound alterations in mineral
      metabolism. A growing body of evidence, based largely on observational studies,
      indicates that patient mortality is associated with altered mineral metabolism.
      Evidence is reviewed concerning the association between mortality and high
      concentrations of serum phosphorus, calcium, calcium-phosphate product, and
      parathyroid hormone. In addition, mortality may be independently associated with
      dialysate calcium concentration, type of phosphate binder therapy, and use of
      vitamin D analogs. Practices related to management of altered mineral metabolism
      may prove to be a promising means of improving outcomes for patients with chronic
      kidney disease.

PMID- 17200040
TI  - Vitamin D in patients with kidney disease: cautiously optimistic.
AB  - Nephrologists are well aware of the therapeutic effects of activated vitamin D in
      managing secondary hyperparathyroidism. Beyond bone and mineral metabolism,
      however, we are now beginning to appreciate the effects of activating the vitamin
      D receptor (VDR) in other cell types. Our group and others recently found a
      survival advantage associated with injectable vitamin D therapy in hemodialysis
      populations. The observational nature of these studies, however, subjects them to
      the possibility that confounding and bias may have accounted for their results.
      Therefore, it is unclear if indeed a survival benefit exists, if harm is incurred
      with this therapy or if activation of the VDR in cell types other than bone,
      intestine, and the parathyroid gland are applicable to our patients with kidney
      disease. The range of studies being planned include those targeting the
      cardiovascular effects of VDR activation, further understanding of the prevalence
      and consequences of vitamin D deficiency in patients with kidney disease, trials
      to examine the effects of VDR activation on intermediate cardiovascular and
      noncardiovascular endpoints, and trials targeting mortality endpoints. If
      consistent with the recent observations, these studies may provide nephrologists
      with an intervention to alter the otherwise poor outcomes in patients with kidney
      disease.

PMID- 17200041
TI  - Bone health in chronic kidney disease-mineral and bone disease.
AB  - Chronic kidney disease (CKD) is accompanied by disturbances in calcium,
      phosphate, vitamin D, and parathyroid hormone (PTH) homeostasis that play an
      important role in the pathophysiology of renal bone disease. The increased
      cardiovascular morbidity and mortality observed among patients with CKD has
      recently been recognized to be associated with these disturbances in mineral
      metabolism. Thus, disturbances in mineral metabolism observed in renal failure
      results in a multisystem disorder, making the development of a standardized
      definition of these disorders a top priority. Therefore, the Board of Directors
      of Kidney Disease: Improving Global Outcomes proposed to define the broader
      category of mineral disorders associated with CKD as CKD-mineral and bone
      disorder (CKD-MBD). This newly proposed definition will include the disorders of
      mineral metabolism, bone histology (renal osteodystrophy), and the extraskeletal
      manifestations such as vascular calcification. This new definition and
      stratification of disease should result in improvement not only in the clinical
      management of patients but also will facilitate the interpretation and
      translation of clinical research. Renal osteodystrophy is now considered as 1
      component of this disorder and will be defined as a morphologic alteration only,
      based on unification of the histomorphometric definitions that will include
      parameters of turnover, mineralization, and volume. An internationally accepted
      classification system will enable the consensus for bone biopsy evaluation as
      well as for the role of biomarkers. This article will focus on the newly proposed
      definitions of bone disease as part of CKD-MBD, based on the complex
      pathophysiologic process underlying bone disease in CKD stages 2 to 5.

PMID- 17200042
TI  - Clinical assessment of vascular calcification.
AB  - Cardiovascular calcification poses an increased risk for cardiovascular events in
      advanced phases of chronic kidney disease. This evidence has brought many
      investigators to focus their attention on the importance of detection of
      calcification and avoidance of further development of it with appropriate
      therapeutic choices. Physicians can use a variety of noninvasive imaging tools to
      identify cardiovascular calcification, some with merely qualitative and others
      with both qualitative and quantitative capabilities. Plain x-rays and
      ultrasonography can be used to identify macroscopic calcification of aorta and
      peripheral arteries, echocardiography is helpful for assessment of valvular
      calcification, and computed tomography technologies constitute the gold standard
      for quantification of cardiovascular calcification. The latter is also useful to
      monitor calcification progression and to assess the effect of different
      therapeutic strategies directed at modifying calcification progression. In this
      article, we review the clinical significance of vascular calcification and some
      of the evidence surrounding the most commonly employed noninvasive imaging
      techniques.

PMID- 17200043
TI  - Management of chronic kidney disease mineral-bone disorder.
AB  - Chronic kidney disease mineral-bone disorder (CKD-MBD) is a systemic disorder of
      abnormal serum levels of mineral-related biochemistries, abnormal bone, and
      extraskeletal calcification. Although we have gained understanding on how these
      components are interrelated, our therapeutic tools remain focused on only one
      aspect of CKD-MBD at a time. However, the management of these disorders is also
      interrelated; treatments may help one aspect of the disorder but cause or
      accelerate another. As such, management remains a major challenge to
      nephrologists and requires balancing risk and benefit of the various available
      therapies. Our challenge for the decade ahead is to determine which combinations
      of therapy can be used safely together to prevent morbidity and mortality in CKD.
      Furthermore, the pathophysiology that sets these events into motion begins well
      before the onset of ESRD. Future therapies and guidelines should, therefore, also
      emphasize the need for earlier detection and management of CKD, shaped by the
      results of valid clinical trials.

PMID- 17200044
TI  - Mechanisms of vascular calcification.
AB  - Vascular calcification is highly prevalent and correlated with high rates of
      cardiovascular mortality in chronic kidney disease patients. Recent evidence
      suggests that mineral, hormonal, and metabolic imbalances that promote phenotype
      change in vascular cells as well as deficiencies in specific mineralization
      inhibitory pathways may be important contributory factors for vascular
      calcification in these patients. This article reviews current mechanisms proposed
      for the regulation of vascular calcification and data supporting their potential
      contribution to this process in chronic kidney disease.

PMID- 17200046
TI  - Calcium in chronic kidney disease: recommended intake and serum targets.
AB  - Abnormal mineral metabolism has the potential to significantly increase mortality
      in patients with chronic kidney disease, especially by the time renal replacement
      therapy is required. While excess phosphorus and hyperphosphatemia have long been
      identified as risks for increased morbidity and mortality, the roles of calcium
      load and serum calcium levels have been less clear. Calcium-based recommendations
      in the K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in
      Chronic Kidney Disease were labeled as expert opinion. The rationale behind the
      opinion-based recommendations is reviewed along with additional supportive
      information that has become available since the bone and mineral guidelines were
      published.

PMID- 17200045
TI  - The ESRD uninsured matter.
AB  - Health-care insurance is the key to health-care access, yet the number of
      uninsured in the United States grows by a million persons per year and consists,
      in large part, of those who are financially unable to obtain medical coverage.
      Their unpaid medical bills add significantly to the cost of health insurance for
      those who do pay. Those without insurance receive care on a sporadic basis, and
      the risk of poor health-care outcomes is well established. The end-stage renal
      disease (ESRD) uninsured face unique problems related to chronicity of care and
      the system of chronic dialysis-care delivery. This article addresses the growing
      challenge of the ESRD uninsured in the United States and describes how the
      current system copes with the ESRD uninsured. More broadly, it discusses who the
      uninsured are (including undocumented immigrants), the health-care consequences
      of being without coverage, and how their care is currently financed. It also
      presents a health-care reform measure in Massachusetts designed to provide
      affordable insurance to those without coverage.

PMID- 17200047
TI  - Chronic kidney disease care and medicare reimbursement for preventive services.

PMID- 17200048
TI  - The prevalence of symptoms in end-stage renal disease: a systematic review.
AB  - Symptoms in end-stage renal disease (ESRD) are underrecognized. Prevalence
      studies have focused on single symptoms rather than on the whole range of
      symptoms experienced. This systematic review aimed to describe prevalence of all
      symptoms, to better understand total symptom burden. Extensive database, "gray
      literature," and hand searches were undertaken, by predefined protocol, for
      studies reporting symptom prevalence in ESRD populations on dialysis,
      discontinuing dialysis, or without dialysis. Prevalence data were extracted,
      study quality assessed by use of established criteria, and studies
      contrasted/combined to show weighted mean prevalence and range. Fifty-nine
      studies in dialysis patients, one in patients discontinuing dialysis, and none in
      patients without dialysis met the inclusion criteria. For the following symptoms,
      weighted mean prevalence (and range) were fatigue/tiredness 71% (12% to 97%),
      pruritus 55% (10% to 77%), constipation 53% (8% to 57%), anorexia 49% (25% to
      61%), pain 47% (8% to 82%), sleep disturbance 44% (20% to 83%), anxiety 38% (12%
      to 52%), dyspnea 35% (11% to 55%), nausea 33% (15% to 48%), restless legs 30%
      (8%to 52%), and depression 27% (5%to 58%). Prevalence variations related to
      differences in symptom definition, period of prevalence, and level of severity
      reported. ESRD patients on dialysis experience multiple symptoms, with pain,
      fatigue, pruritus, and constipation in more than 1 in 2 patients. In patients
      discontinuing dialysis, evidence is more limited, but it suggests they too have
      significant symptom burden. No evidence is available on symptom prevalence in
      ESRD patients managed conservatively (without dialysis). The need for greater
      recognition of and research into symptom prevalence and causes, and interventions
      to alleviate them, is urgent.

PMID- 17200049
TI  - End-stage renal disease use in hurricane-prone areas: should nephrologists
      increase the utilization of peritoneal dialysis?
AB  - Hurricane Katrina resulted in massive destruction of the gulf coast of the United
      States in 2005. In the immediate aftermath, displaced dialysis patients required
      urgent hemodialysis or additional peritoneal dialysis (PD) supplies. Massive
      damage to the health care infrastructure in these communities disrupted dialysis
      services for several months. As a result of this event and subsequent storms
      during the 2005 Atlantic hurricane season, many decisions regarding future
      services to dialysis patients in hurricane prone communities (HPCs) need to
      occur. Nephrologists, dialysis nurses, dialysis providers, and patients need to
      discuss the ramifications of and types of continued dialysis services in HPC.
      Nephrologists should encourage PD, and efforts to educate on other renal
      replacement therapies including PD and transplant should occur. With the
      potential for interruption of electrical, sewerage, and water services, more
      patients should consider PD. Recovery from future events begins with appropriate
      disaster planning. Many questions are considered and need answering in planning
      for dialysis services in HPC and other communities subject to natural disasters.
      This summary provides the basis to begin discussions when planning for dialysis
      services in communities prone to natural disasters.

PMID- 17200050
TI  - Stabilization of glomerular filtration rate in advanced chronic kidney disease: a
      two-year follow-up of a cohort of chronic kidney disease patients stages 4 and 5.
AB  - This study examines whether stabilization of the glomerular filtration rate (GFR)
      is possible in patients with advanced chronic kidney disease (CKD), managed in a
      CKD clinic. A cohort of 82 patients with stages 4 and 5 CKD was followed for a
      period of 2 years after initiation of erythropoietin for anemia to determine the
      GFR and the frequency of primary outcomes (dialysis, transplantation, or death).
      GFR, calculated by the abbreviated Modification of Diet in Renal Disease formula,
      was determined every 3 months. After 24 months, 35 subjects (43%) developed a
      primary outcome. Controlled for other risk factors, the risk of having a primary
      outcome increased 19.7% for every unit that the GFR decreased (95% confidence
      interval [CI], 11.9%-26.8%, P < .001) and decreased 21.7% for every unit that the
      hemoglobin increased (95% CI, 0.5%-38.4%, P < .001). Blacks had a 3.1 times
      higher risk (95% CI, 1.4-6.9, P = .006) of developing a primary outcome than
      other ethnicities. In subjects who did not develop primary outcomes (n = 47 or
      57%), GFR remained unchanged (19.5 +/- 9.1 at the end of the study v 20.8 +/- 5.3
      mL/min/1.73 m(2) at baseline, P = .16). The standardized mortality rate was 4.75
      and 9.77 per 100 person-year for stages 4 and 5, respectively. We conclude that
      stabilization of GFR over a 2-year period can be achieved in many patients with
      advanced CKD treated with erythropoietin in a CKD clinic. Although the precise
      reason for the stabilization of GFR cannot be elucidated from this study, our
      data are "proof of concept" that CKD outcomes can be improved in a CKD clinic
      setting.

PMID- 17200051
TI  - Parental knowledge of child sexual abuse symptoms.
AB  - The purpose of this study was to investigate parental knowledge of symptoms of
      child sexual abuse (CSA), and to determine the factors associated with that
      knowledge. A total of 150 parents listed symptoms of CSA in the following areas:
      physical/medical, emotional, sexual behavior, and behavior towards others.
      Results suggest that, although most parents are familiar with some of the
      symptoms of CSA, they are more likely to know emotional or behavioral reactions
      which could be suggestive of many other life stressors. Parents with higher
      socioeconomic status listed more symptoms, but race and parenting experience were
      not significant factors. Results suggest the need to inform parents of more
      indicative physical or sexual symptoms, and to target parents of lower SES
      background in awareness efforts. doi:10.1300/ J070v15n04_01.

PMID- 17200052
TI  - Sibling incest: reports from forty-one survivors.
AB  - An exploratory study was conducted with a convenience sample of 41 adult
      survivors of sibling incest using a retrospective survey design. Participants
      were interviewed about their childhood sexual experiences with a sibling. Most
      participants reported vaginal or oral intercourse and coercive experiences. Half
      of the sample reported sexual experiences with family members, as well as other
      child abuse. Half of the participants showed evidence of distorted beliefs about
      child sexual abuse. Disclosure of the incest during childhood was rare.
      doi:10.1300/ J070v15n04_02.

PMID- 17200053
TI  - Therapy for child sexual abuse:women talk about helpful and unhelpful therapy
      experiences.
AB  - Women with histories of childhood sexual abuse (CSA) were asked to describe what
      was helpful and unhelpful to them in therapy. From 191 completed postal
      questionnaires, a subsample of 20 participants was interviewed. This paper
      focuses on three specific areas of therapy raised by interviewees: (1)
      Establishing a therapeutic relationship; (2) talking about experiences and
      effects of CSA; and (3) dealing with errors in therapy. Findings suggest that to
      avoid making serious therapy errors, therapists (1) need special skills to be
      aware of the dynamics and effects of CSA and of abuse-focused therapy and to deal
      with abuse-related material, and (2) need to develop an equal and open therapy
      relationship that includes ongoing consultation with clients about their
      experiences of therapy. doi:10.1300/J070v15n04_03.

PMID- 17200054
TI  - How child protective services investigators decide to substantiate mothers for
      failure-to-protect in sexual abuse cases.
AB  - The purpose of this study was to determine how Child Protective Services (CPS)
      investigators decide to substantiate mothers for failure-to-protect from sexual
      abuse. A case-comparison study was used to compare 31 mothers who were and 62
      mothers who were not substantiated for failure-to-protect by CPS. The
      multivariate analysis showed that mothers who did not consistently believe the
      sexual abuse occurred and who did not consistently act protectively were more
      likely to be substantiated. In addition, if they knew about the abuse from more
      than one source were less supportive of the children; and had a substance abuse
      problem, a mental health problem or were being battered, then they were more
      likely to be substantiated. Investigators appear to apply criteria consistently
      to substantiate mothers. doi:10.1300/J070v15n04_04.

PMID- 17200055
TI  - Comments on how child protective services investigators decide to substantiate
      mothers for failure-to-protect in sexual abuse cases.
AB  - This commentary discusses the decisions of child protective service (CPS)
      investigators to substantiate mothers for failure to- protect (FTP) in child
      sexual abuse cases. Four areas are identified in which the scientific literature
      remains inadequate to fully inform child maltreatment researchers, CPS
      practitioners and child welfare policymakers on models and outcomes for FTP
      substantiation decisions. Attention is called to the need for more information
      about how differences in statutory definitions, common guidelines, and
      professional education and training influence FTP substantiation decisions.
      Current gaps in the knowledge base on FTP and nonoffending caregivers are
      highlighted. doi:10.1300/J070v15n04_05.

PMID- 17200056
TI  - Caregiver support and child sexual abuse: why does it matter?

PMID- 17200057
TI  - Commentary on how child protective service investigators decide to substantiate
      mothers for failure to protect in sexual abuse cases.

PMID- 17200058
TI  - The other side of child neglect charges: what happens when there are no standard
      criteria for charging a non-offending mother with neglect?

PMID- 17200060
TI  - Social support promoting health in older women.
AB  - Given the aging of women and their increased risk for health problems, it is
      important to explicate factors that may foster health promotion. While social
      support has been a concept of interest in predicting health promotion in women,
      the concept has been inconsistently defined and poorly explicated. A qualitative
      study was conducted to describe the types and processes of social support for
      health promotion in older women. Focus group interviews with 51 women, aged 55
      93, were held. Data were analyzed using open coding to categorize data with
      attention to consistency and variance. Data explicated aspects of social support
      unique to health promotion in community-dwelling older women. Broad categories
      identified included connectedness and collectivism. Findings validate existing
      conceptualizations and provide an expanded perspective of social support by
      demonstrating aspects of support unique to the social context of older, community
      dwelling women. Findings also provide a basis for development of socially
      relevant interventions designed to promote health and optimize health outcomes in
      older women.

PMID- 17200061
TI  - Past-users of HRT are osteopenic four months after discontinuation:an
      observational and cross-sectional study.
AB  - Hormonal replacement therapy (HRT) helps to prevent osteoporosis. The effect of
      short-term discontinuation of a long-term HRT on bone mineral density (BMD) in
      healthy post-menopausal women is unknown. Fifteen women on HRT (HRT users), 17
      who never used HRT (non-users) and 8 former HRT users (past-HRT users) were
      recruited. BMD was measured by DXA. Our results allow to hypothesize that BMD may
      decline after short-term HRT discontinuation, which would increase the fracture
      risks. Indeed, our results show that past-HRT users are osteopenic just as non
      users. However, these results should be re-examined using a prospective trial and
      a larger sample size.

PMID- 17200062
TI  - Treatment decision-making among older women with breast cancer.
AB  - This study examined breast cancer treatment decision-making among older adults,
      including professional and lay involvement. Thirty respondents were interviewed
      for this study; cancer survivors (70%) and newly diagnosed (30%) women with
      breast cancer. Respondents reported making treatment decisions in consultation
      with their oncologists. However, women differed on the extent to which they
      perceived their participation in the treatment process. Respondents' oncologists
      appear to be the primary factor associated with older women's breast cancer
      surveillance decision-making and adherence. The influence of women's support
      systems on their treatment decisions and surveillance activities appears to be
      minimal. Informal support systems, however, likely enhance women's ability to be
      active participants in their care. The growing need for interventions which
      target older women has been indicated. Interventions, however, cannot be
      adequately developed without first identifying the physical and psychosocial
      phenomena which affect decision-making.

PMID- 17200063
TI  - Configurations of informal social support among older lesbians.
AB  - Limited research has been conducted on the needs and concerns of older lesbians
      in the American population. The purpose of this paper is to present findings from
      a qualitative study of older (aged 55 and older) lesbians' experiences of and
      perspectives on aging, with a focus on their discussions of social support.
      Through an in-depth qualitative study with 25 older lesbians, we found that aging
      lesbians may be less likely to access formal social services due to perceptions
      of bias within the services and a potential lack of connection with those who do
      use services. However, participants were creative at formulating informal
      networks of support. Four heuristic categories (empowered, secure, independent,
      and precarious) of informal social support were developed to characterize the
      various ways in which participants configured their support systems. Social
      support within each category was conceptualized both in terms of intentionality
      and degree of connectedness. Being partnered did not necessarily equate with a
      strong sense of social support. Further research needs to be conducted on older
      lesbians in order to better characterize and respond to their needs as they age.

PMID- 17200066
TI  - Fostering social work gerontology competence: A collection of papers from the
      First National Gerontological Social Work Conference, February 27-March 2, 2003,
      Atlanta, Georgia, USA.

PMID- 17200064
TI  - Experienced health in older women with rheumatoid arthritis.
AB  - This study explored how older women with chronic illness and disability
      experience their own health. Data were collected in in-depth interviews with ten
      older women with rheumatoid arthritis. Data analysis and interpretation was
      carried out within a phenomenological- hermeneutic frame of understanding, which
      revealed five major themes: health as coping with everyday life, health as
      freedom, health as absence of inconvenience, health as togetherness and health as
      mental well-being. For older people with chronic illness and disability, good
      health found expression in general well-being. It was perceived as a state of
      equilibrium that the respondents sought to maintain through their own active
      choices.

PMID- 17200067
TI  - Developing visibility for aging in social work: the first NGSWC.
AB  - In March 2001, the Council on Social Work Education's (CSWE) Strengthening Aging
      and Gerontology Education for Social Work (SAGE-SW) project published an action
      agenda for social work and aging (CSWE/SAGE-SW, 2001). CSWE SAGE-SW, funded by
      the John A. Hartford Foundation from 1998 to 2004, had several charges in the
      first phase of funding, including the gathering of data through a thorough review
      of literature, focus groups, surveys and a variety of activities to garner expert
      input. This agenda, often referred to as the Blueprint, identified a number of
      serious issues regarding the lack of attention, preparation, leadership and
      interest in aging within the social work profession. It also provided some
      recommended actions to address these issues and help set the stage for the
      creation of the National Gerontological Social Work Conference. What were the
      issues at hand and why might a National Gerontological Social Work Conference
      (NGSWC) address some of these issues?

PMID- 17200068
TI  - Creating aging-enriched social work education:a process of curricular and
      organizational change.
AB  - The CSWE Geriatric Enrichment in Social Work Education Project, funded by the
      John A. Hartford foundation, aimed to change curricula and organizational
      structure in 67 GeroRich projects so that all students would graduate with
      foundation knowledge and skills to work effectively with older adults and their
      families. The emphasis was on change processes to infuse and sustain
      gerontological competencies and curricular resources in foundation courses. This
      article presents lessons learned and strategies for engaging faculty,
      practitioners and students in the curriculum and organizational change process.

PMID- 17200069
TI  - Infusing gerontology throughout the BSW curriculum.
AB  - How can social work educators ensure that all of their BSW students have the
      savvy and "know-how" to deal with the needs of our growing aging population? The
      development of broad-based, innovative gerontological learning opportunities in a
      BSW program in a small liberal arts and sciences college is presented in this
      article. Strategies for actively involving community representatives in
      curriculum changes and participatory learning experiences with students are
      shared. Ways to incorporate various disciplines in the BSW education are explored
      in addition to developing intergenerational projects, direct involvement of older
      persons in the educational process, and ways to unite field practice with theory.

PMID- 17200070
TI  - Strengthening aging content in the baccalaureate social work curricula: what
      students have to say.
AB  - Encouraging student's interest and preparing them for social work practice with
      older adults is increasingly important in view of the demographic changes that
      are taking place. This article describes a study that engages BSW students in a
      discussion of best models for promoting gerontological social work curriculum
      infusion. Using two focus groups, the authors explore barriers to student
      interest and potential strategies to recruit students for gerontological social
      work. Fear of their own decline and mortality, lack of exposure to older adults
      and aging issues emerge as the primary reasons for aversion to working with older
      adults. Strategies to promote student interest, organize curricula, and create an
      inclusive learning context are discussed.

PMID- 17200071
TI  - Geriatric enrichment: guaranteeing a place for aging in the curriculum.
AB  - Two years ago, the School of Social Work embarked upon a new and challenging
      initiative to create sustainable structural changes that enrich gerontological
      learning experiences for all our BSW and MSW students, faculty, fieldwork
      instructors and community practitioners. We envisioned that participation in this
      initiative would enable us to expand and embed geriatric content in the
      undergraduate and graduate curriculum, to increase our geriatric fieldwork
      placement opportunities, to evaluate and enhance our teaching and learning
      resources on aging, and to develop two new aging specific courses. Having reached
      our third year of operation, we find ourselves reflecting on what have been our
      successes, what could we have done differently, and where do we go in the future.
      This article will describe our process of developing a model of curriculum change
      that will guarantee a place for aging in both our undergraduate and graduate
      curricula.

PMID- 17200072
TI  - Building on the life-span perspective: a model for infusing geriatric social
      work.
AB  - The growth in the older adult population and the demand for better trained
      geriatric social workers challenge the existing curricula of social work
      programs. The Geriatric Enrichment Grant funded by the John A. Hartford
      foundation has provided financial support for curricular reform. Curriculum
      reform is a challenging undertaking at any level. Each program and educational
      institution experiences the process of curriculum reform in unique ways. This
      paper describes one program's experience of curriculum reform for the purpose of
      infusing geriatric content.

PMID- 17200073
TI  - Increasing aging content in social work curriculum: perceptions of key
      constituents.
AB  - This mixed methodology study examines the perceptions of key constituents
      regarding methods for effectively integrating aging content into the foundation
      curriculum of the BSW and MSW program at the University of Georgia School of
      Social Work. Students were asked to complete a survey to determine their
      perception of geriatric content that existed within the foundation coursework.
      Following an analysis of the survey results, eight semi-structured focus group
      discussions were conducted with a purposeful sample of students, faculty, field
      instructors, social work alumni, older adults from the community, and
      representatives from aging agencies. The intention of these focus groups was to
      find out what aging content should be infused within the curriculum. The focus
      group meetings were held in various locations throughout Northeast Georgia and in
      one remote location in South Georgia. Participants were interviewed about the
      necessary skills and knowledge for social workers practicing with an aging
      population in the areas of: essential intervention skills, program policies and
      regulations, critical information needed to develop client service plans,
      strategies for addressing service delivery fragmentation, and community
      collaboration to support intergenerational family needs. The results of this
      study will be discussed to provide suggestions on how existing foundation courses
      can integrate aging content.

PMID- 17200074
TI  - A competency approach to curriculum building: a social work mission.
AB  - This article discusses The John A. Hartford Foundation CSWE SAGE-SW Project
      through an historical reflection of curriculum development within the profession.
      The project's relationship to several curriculum building models is also
      explored. A curriculum development tool for combining the Hartford Competencies
      with theCSWEEPAS requirements is provided.

PMID- 17200075
TI  - Transforming the curriculum through the intergenerational lens.
AB  - Our society is aging at a rapid rate and with this trend comes many of the social
      and economic demands that the profession of Social Work addresses. Akey dilemma
      of the profession is how to interest and educate undergraduate social work
      students in aging and gerontology so that the needs of elderly can be supported.
      Social Work students notoriously are primarily interested in working with
      children and adolescents. With the support of the John A. Hartford Foundation's
      Geriatric Enrichment in Social Work Education grant, the authors developed a
      Spiral Perspective to infuse intergenerational content into the curriculum of
      their department and to give students exposure to geriatric content throughout
      their educational experience.

PMID- 17200076
TI  - Developing geriatric social work competencies for field education.
AB  - Preparing social workers to effectively practice with the growing older
      population requires the identification of geriatric competencies for the
      profession. The John A. Hartford Geriatric Social Work Initiative provided the
      impetus and direction for a national strategy to improve the quality of
      preparation of geriatric social workers. The Geriatric Social Work Practicum
      Partnership Program (PPP) is the project with the Hartford Initiative that
      emphasizes field education. The Geriatric Social Work Education Consortium
      (GSWEC), one of the PPP programs, initiated the development of competencies for
      work with older adults. GSWEC utilized Geriatric Social Work White Papers and the
      pioneering work of the Council on Social Work Education's (CSWE) Strengthening
      Aging and Gerontology Education for Social Work's (SAGE-SW) comprehensive
      competency list as well as conducted focus groups locally to delineate key
      competencies for field education. The Coordinating Center for the PPP, located at
      the New York Academy of Medicine, led in collaboratively developing knowledge
      based skill competencies for geriatric social work across all 6 demonstration
      sites (11 universities). The competencies adopted across sites include skills in
      the following five major domains: values and ethics; assessment (individuals and
      families, aging services, programs and policies); practice and interventions
      (theory and knowledge in practice, individual and family, aging services,
      programs and practice) interdisciplinary collaboration; and evaluation and
      research. The identified competencies have proven effective in evaluating
      students (n = 190) pre- and post PPP field education. The implications for
      further development of competency driven education for geriatric social work are
      discussed.

PMID- 17200077
TI  - Intergenerational service-learning: an innovative teaching strategy to infuse
      gerontology content into foundation courses.
AB  - This article provides an overview of intergenerational service- learning, an
      experiential pedagogy that involves students in learning outside the traditional
      classroom while providing a needed service in the community. Examples of
      intergenerational service-learning projects are presented that have been
      successfully utilized by the authors. These projects demonstrate the importance
      of using reflective practice assignments to help students deconstruct and
      reconstruct images, beliefs and paradigms about older adults. In addition,
      problems and opportunities in developing service-learning projects in urban and
      rural settings and with the Hispanic community are described, as well as some of
      the types of learning that may result from implementing service-learning
      experiences in various social work foundation courses.

PMID- 17200078
TI  - Increasing aging and advocacy competency: the intergenerational advocacy pilot
      project.
AB  - The Council on Social Work Education's (CSWE) Strengthening Aging and Gerontology
      Education for Social Work (SAGE-SW) project, funded by the John A. Hartford
      Foundation partnered with the National Committee to Preserve Social Security and
      Medicare (NCPSSM) to develop an Intergenerational Policy and Advocacy Project
      (IAP). This curriculum pilot project, based on a community organization model,
      was conducted with 13 baccalaureate social work (BSW) and master's social work
      (MSW) programs across the country and 122 students. The project was one method to
      pursue CSWE SAGE-SW's efforts to infuse aging content into social work foundation
      curricula, to support intergenerational teaching, to strengthen social work
      advocacy skills, and to provide social work students with positive experiences
      working with older adults. Pilot sites were asked to carry out the project as
      part of an existing course foundation or field practicum course. Project
      activities included collaboration with a variety of community agencies, holding
      issues or "town hall" forums in order to educate community members about critical
      policy issues affecting older adults; making contacts and establishing
      relationships with local, state and/or federal legislators; and conducting
      assessments of the service needs of older adults in the students' communities.
      Questionnaires, feedback, pre-post evaluations as well as brief accounts of each
      project are presented. Participants considered the IAP to be a successful project
      in terms of the objectives of increasing awareness and competency among social
      work students of aging issues and of promoting intergenerational linkages between
      older people and social work students.

PMID- 17200079
TI  - Developing an aging prepared community: collaboration among counties, consumers,
      professionals and organizations.
AB  - This paper reports on a collaborative process to create an "aging prepared
      community" in a four county region. The process benefited from a generous grant
      from the John A. Hartford Foundation that supported an 18 month planning period
      which included input from service providers and a vast array of aging persons and
      their families, including particular efforts to reach underserved populations
      from multicultural, inner- city and rural communities. Under the umbrella of the
      Elder Network of the Capital Region, the process is now beginning its
      implementation period with foci on the following: linking health, social service
      and faith communities; developing accessible health education and wellness
      programs; creating and implementing a regional system of information and
      assistance; and mounting a media campaign.

PMID- 17200080
TI  - Social work and aging in the emerging health care world.
AB  - Social work practice with older adults and their families is increasingly
      recognized by the profession as a major field of practice in a wide range of
      health care and community-based settings. This article reviews emerging trends
      and issues in the fields of aging and health care, drawing on gerontological
      health care research which bridges these areas. Given the growing number and
      diversity of older adults in our society, and dramatic changes in the
      organization and delivery of health care, the authors suggest skills and
      competencies essential to enhancing the well-being of older adults and their
      families in the 21st Century.

PMID- 17200081
TI  - End-of-life care and social work education: what do students need to know?.
AB  - Social workers are major service providers to people who are facing end-of-life
      issues including the terminally ill and their families. Yet, exemplary models for
      social work education and intervention methods are limited in rural states. A
      statewide survey conducted in Kentucky found only two social work courses
      dedicated to end-of-life care currently being offered by accredited undergraduate
      and graduate institutions. Another statewide survey found that many hospice
      social workers are relatively inexperienced and have a need and desire for more
      education on death, dying and loss. Also, unique cultural, economic and
      geographic areas, such as Appalachia are enigmas when it comes to the provision
      of end-of-life care. This partnership provides a varied perspective on delivery
      of end-of-life care services with an emphasis on social work interventions and
      education.

PMID- 17200082
TI  - Environmental issues affecting elder abuse victims in their reception of
      community based services.
AB  - This study examined the dominant factors that predict the utilization of services
      by 129 identified elder abuse victims who reside in the community. Utilizing the
      Andersen Model, services accepted or rejected were analyzed from individual,
      family and environmental perspectives. Results indicated that service utilization
      is related to three "need" factors: (1) Victim has cognitive and ADL impairments,
      (2) Victim has poor health status (self rated), and (3) The abuser is financially
      dependent on the victim and is also the primary caregiver of the victim.
      "Enabling" factor (1) Victim lives alone. "Predisposing" factors (1) Abuser is
      substance abuser and (2) Abuser is female. A great proportion of the elder abuse
      victims in this study accepted services from an agency that provided a single
      entry point into the service system and had highly trained personnel utilizing a
      case management approach.

PMID- 17200083
TI  - Research, macro practice and aging in the social work education curriculum.
AB  - This paper presents a model that used a macro emphasis for teaching research
      using older adults. Faculty developed the teaching model to address three key
      areas of concern in the education of Bachelor of Social Work (BSW) students for
      generalist practice: (1) research, (2) macro-level practice, and (3) aging. The
      paper explores the nature of these concerns and draws upon previous literature to
      delineate a teaching model designed to strengthen these areas of generalist
      practice by integrating content on macro-level concerns and aging into the
      curriculum of a research course. The development and evaluation of the research
      course within the context of a community and college project are described, as
      are the benefits for students, the social work program and the community.
      Preliminary findings indicate some support for the use of such a model.

PMID- 17200084
TI  - Insights into material and structural basis of bone fragility from diseases
      associated with fractures: how determinants of the biomechanical properties of
      bone are compromised by disease.
AB  - Minimal trauma fractures in bone diseases are the result of bone fragility.
      Rather than considering bone fragility as being the result of a reduced amount of
      bone, we recognize that bone fragility is the result of changes in the material
      and structural properties of bone. A better understanding of the contribution of
      each component of the material composition and structure and how these interact
      to maintain whole bone strength is obtained by the study of metabolic bone
      diseases. Disorders of collagen (osteogenesis imperfecta and Paget's disease of
      bone), mineral content, composition and distribution (fluorosis and
      osteomalacia); diseases of high remodeling (postmenopausal osteoporosis,
      hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis,
      pycnodysostosis); and other diseases (idiopathic male osteoporosis,
      corticosteroid-induced osteoporosis) produce abnormalities in the material
      composition and structure that lead to bone fragility. Observations in patients
      and in animal models provide insights on the biomechanical consequences of these
      illnesses and the nature of the qualities of bone that determine its strength.

PMID- 17200085
TI  - Genetics and gender in cardiothoracic and vascular anesthesia.

PMID- 17200086
TI  - Genomics basics: DNA structure, gene expression, cloning, genetic mapping, and
      molecular tests.
AB  - Genomics is the study of the structure and function of the human genome including
      genes and their surrounding DNA sequences. The over 3 billion base pairs of the
      human genome have now been sequenced and approximately 25,000 genes acknowledged.
      However, only 1% of the entire genome has been assigned to protein coding and
      decades more work is anticipated to define the functional relevance of noncoding
      DNA as well as the basis and consequences of sequence variations among
      individuals. For medical scientists, the focus remains on discovering both
      disease-causing and disease-susceptibility genes. For pharmaceutical companies,
      the opportunity to develop molecularly targeted therapy is not going unnoticed.
      For the practicing physician, the prospect of genomic medicine that incorporates
      molecular diagnosis and pathogenesis-targeted therapy requires basic
      understanding of terminology and concepts in molecular biology and the
      corresponding laboratory tests.

PMID- 17200087
TI  - Genetic influences on cerebral outcome after cardiac surgery.
AB  - Just as the influence of genetic variation on patient outcomes is being discussed
      in many other areas of medicine, so too are its effects on cerebral outcome after
      cardiac surgery now being described. Whereas early studies focused on
      neurocognitive outcome, where the single nucleotide polymorphisms of APOE4 and
      PL(A2) were the first investigated genetic targets, stroke is now being
      elaborated on with related single and multi-gene single nucleotide polymorphisms
      having been identified. Our work has established key links between post-cardiac
      surgery stroke and C-reactive protein (3'UTR 1846C/T) and interleukin-6 (-174
      G/C) single nucleotide polymorphisms.

PMID- 17200089
TI  - The genetic determinants of renal impairment following cardiac surgery.
AB  - Cardiac surgery is frequently performed, and acute renal dysfunction is a common
      adverse event following this procedure. Cardiac surgery-related renal injury
      independently predicts longer hospital stays and greater rates of morbidity and
      mortality. Although much work has been completed toward better understanding of
      this phenomenon, the state of knowledge concerning surgery-related renal injury
      remains limited. Currently, there is no effective paradigm to identify patients
      who are at risk for this condition; the specific mechanisms of renal injury
      during surgery are incompletely understood; and few therapies exist to prevent or
      treat this phenomenon. To better understand this common clinical problem, recent
      research has focused on the importance of genetic variability within the
      physiological and patho-physiological systems that underlie renal dysfunction
      following cardiac surgery. Emphasizing the importance of using genetics to
      elucidate molecular mechanisms of this disease, this article reviews the current
      literature on genetic polymorphisms and post cardiac surgery-related renal
      dysfunction.

PMID- 17200088
TI  - Genetics of coagulation: considerations for cardiac surgery.
AB  - Genetic variants in the coagulation system have been known since antiquity.
      Today, because of modern improvements in diagnosis and medical management, the
      clinician is likely to encounter a spectrum of coagulation factor deficiencies
      and identified polymorphic variants in the surgical population. Because
      perioperative hemorrhagic and thrombotic complications are potentially serious,
      it is important to understand the role that these defects and variants may play
      in predicting risk and optimizing patient management. The implications of
      coagulation genetics on the perioperative management of the cardiac surgery
      patient are reviewed.

PMID- 17200090
TI  - Genetics of postoperative complications following thoracic surgery.
AB  - The field of complex trait-gene interaction research has expanded exponentially
      in recent years, and new insights into the ways patients respond to surgical
      stimuli have arisen from this body of work. From a physiological systems
      perspective, thoracic surgical procedures (thoracotomy in particular) represent a
      massive input stimulus, and it is, therefore, not surprising that approximately
      30% of these patients experience an adverse postoperative event. The best risk
      prediction models have typically explained about 60% to 70% of the risk, leaving
      a large residual component unaccounted for. It is quite possible that there is a
      genetic (heritable) component to this residual risk. This article explores some
      of the concepts underlying gene-disease interactions, the preliminary work that
      has been done to date in this area, and finally discusses some of the more
      important methodological issues involved in complex trait association study
      design.

PMID- 17200092
TI  - On being comfortable with being uncomfortable: centering an Africanist vision in
      our gateway to global health.
AB  - African identity must be central to research on African health and development.
      This article focuses on three primary themes for advancing a different vision for
      understanding health issues in Africa. The first is the need to deconstruct
      conventional assumptions and theories that have been used to frame public health
      problems and solutions in Africa. The second is to insist that identity be
      central to how we frame issues of health and behavior in general and in Africa in
      particular. The third is the importance of the notion of "social cultural
      infrastructure" in defining African ways of knowing to guide public health
      research and intervention in Africa. Finally, the metaphor of the "African gate"
      is used to illuminate these themes while drawing on examples from an HIV- and
      AIDS-related stigma research in South Africa and its implications for addressing
      the critical global public-health issues of today.

PMID- 17200091
TI  - Inhaled milrinone: a new alternative in cardiac surgery?
AB  - The administration of milrinone through inhalation has been studied in only a few
      animal and human studies. Compared to the intravenous administration, inhaled
      milrinone has been shown to reduce pulmonary artery pressure without systemic
      hypotension. Therefore, this approach could represent an alternative to nitric
      oxide. This current state of knowledge of intravenous and inhaled milrinone is
      presented and summarized.

PMID- 17200094
TI  - Using narrative communication as a tool for health behavior change: a conceptual,
      theoretical, and empirical overview.
AB  - Narrative is the basic mode of human interaction and a fundamental way of
      acquiring knowledge. In the rapidly growing field of health communication,
      narrative approaches are emerging as a promising set of tools for motivating and
      supporting health-behavior change. This article defines narrative communication
      and describes the rationale for using it in health-promotion programs, reviews
      theoretical explanations of narrative effects and research comparing narrative
      and nonnarrative approaches to persuasion, and makes recommendations for future
      research needs in narrative health communication.

PMID- 17200093
TI  - Engaging parents in preventive parenting groups: do ethnic, socioeconomic, and
      belief match between parents and group leaders matter?
AB  - The authors evaluate the relation of ethnic, socioeconomic status (SES), and
      belief match between parents and group leaders and engagement in a preventive
      intervention for parents of preschoolers. Engagement was assessed through
      attendance, retention, and quality of participation in sessions with 171 parents
      and 11 group leaders. SES match predicted attendance, retention, and quality of
      participation. Parents attended more sessions, remained longer in the program,
      and participated more actively when their group leader came from comparable SES
      backgrounds. Ethnic match predicted retention only, with parents attending longer
      when their ethnicity matched their group leader's. Engagement was unrelated to
      the extent of match across different characteristics, nor was the link between
      ethnic match and retention mediated by SES or belief match. Results suggest that
      social, cultural, and belief similarities between parents and group leaders may
      be less salient in preventive parenting interventions than is assumed.
      Implications for research and practice are discussed.

PMID- 17200095
TI  - A psychoeducational program to prevent aggressive behavior among Japanese early
      adolescents.
AB  - This study evaluates the impact of a school-based intervention program on
      aggressive behavior among junior high school students in Japan. One hundred and
      four seventh-graders were enrolled in the program and completed Time 1, Time 2,
      and Time 3 surveys. The program was implemented in two classes between Time 1 and
      Time 2 surveys (the first treatment group) and in two other classes between Time
      2 and Time 3 surveys (the delayed treatment group). The program included four
      weekly lessons related to problem solving, stress management, and communication.
      The initial intervention group reported a significant increase in appropriate
      relationships with classmates. Aggressive behavior significantly decreased from
      Time 1 to Time 3 in both groups and from Time 2 to Time 3 in the delayed
      treatment group, but no treatment group effect was noted. Additional modification
      of the program may be needed to achieve decreases in aggressive behavior.

PMID- 17200096
TI  - Process evaluation of an effective church-based diet intervention: Body & Soul.
AB  - Body & Soul has demonstrated effectiveness as a dietary intervention among
      African American church members. The process evaluation assessed relationships
      between program exposure and implementation factors and study outcomes and
      characterized factors important for adoption, implementation, and maintenance.
      Data sources included participant surveys and qualitative interviews with program
      staff, church liaisons, and volunteer advisors who conducted motivational
      interviewing (MI) calls. Outcomes included changes in dietary intake and
      psychosocial variables. Process variables included program exposure,
      participation, and dose and perceptions about MI calls. Results showed that
      attendance at project events, receiving educational materials, and self-reported
      quality of the MI calls were associated with significantly (p < .05) greater
      fruit and vegetable intake, decreased fat consumption, and other secondary
      outcomes. Interviews indicated implementation and sustainability issues and needs
      including more training to enhance MI implementation as well as ongoing support
      and resources. The results have implications for future dissemination efforts of
      Body & Soul.

PMID- 17200097
TI  - Development of scales measuring the capacity of community-based initiatives.
AB  - This article describes the development of two measures for the capacity of local
      public health initiatives. Data obtained from a qualitative study of eight
      community-based initiatives served as the basis for the development of a survey
      instrument. It was administered to a national sample of both leaders and
      nonleaders of 291 such initiatives. Because survey results for leaders and
      nonleaders differed, results could not be combined into a single data set for
      analysis. Results for each data set were analyzed by employing exploratory
      principal components and factor analyses. A 44-item, six-factor scale resulted
      for leaders and a 38-item, five-factor scale resulted for nonleaders. The high
      degree of overlap (22 items) between the two scales resulted in a combined 60
      item instrument that can be administered to both leaders and nonleaders but
      analyzed separately.

PMID- 17200098
TI  - Smoking among low-income pregnant women: an ethnographic analysis.
AB  - This article presents findings from a qualitative study of 53 low-income women
      who were smokers at the onset of pregnancy. Study participants were interviewed
      during pregnancy to document smoking trajectories and factors contributing to, or
      undermining, harm reduction and quit attempts. Thirty percent of women quit
      smoking completely, 43% engaged in sustained harm reduction, and 26% reduced
      their smoking levels intermittently. Case studies of women are presented to
      illustrate reasons for quitting, harm reduction practices, and factors
      influencing relapse and smoking continuation. Women's motivations to quit are
      highlighted. Moral identity as a mother was found to be a key motivating factor
      behind women's quit attempts. Future programs targeting this population would do
      well to acknowledge moral identity as an issue and recognize the challenges of
      quitting for women with limited social support and little control over their
      immediate environment.

PMID- 17200099
TI  - Validation of a Parent-Adolescent Communication Scale for use in STD/HIV
      prevention interventions.
AB  - This study reports on the validation of a scale to assess adolescent girls'
      frequency of sexual communication with their parents. The Parent-Adolescent
      Communication Scale (PACS) was administered to 522 African American female
      adolescents ranging in age from 14 to 18. The PACS demonstrated satisfactory
      internal consistency (across multiple administrations) and acceptable test-retest
      reliability over a 12-month follow-up period. Concurrently, scores on the PACS
      were correlated with frequency of sexual communication with partner, sexual
      communication self-efficacy (boyfriend), perceived parental knowledge, family
      support, depression, and condom use with steady male sex partners. Prospectively,
      baseline PACS scores were correlated with frequency of sexual communication with
      partner and condom use. The present investigation indicates that the PACS is a
      reliable and valid measure of frequency of sexual communication between female
      adolescents and their parents. Utility of the PACS for researchers and
      practitioners is discussed.

PMID- 17200100
TI  - Weapon carrying in Israeli schools: the contribution of individual and school
      factors.
AB  - The present study employed an ecological perspective to examine the relative
      predictive power of individual and school contextual factors on weapon carrying
      at school. The study is based on a nationally representative sample of 10,400
      students in Grades 7 through 11 in 162 schools across Israel. Hierarchical
      logistic modeling examined the relationships between students and school-level
      variables and carrying weapons to school (guns, knives, and other weapons). The
      authors found that school context is associated with weapon carrying and
      increases the likelihood of having students with weapons in the school. For
      instance, schools with a large proportion of students from low-socioeconomic
      status (SES) families showed higher levels of weapon carrying. Furthermore,
      individual factors, such as victimization and fear, are positively associated
      with weapon carrying in school. The discussion highlights the importance of
      improving school climate to deal more effectively with weapon carrying to school.

PMID- 17200101
TI  - Statewide implementation of the 1% or Less Campaign.
AB  - The 1% or Less Campaign is an effective research-tested program for reducing
      saturated fat intake by encouraging individuals to switch to low-fat milk. All
      published studies have been conducted in small communities with mostly White
      populations. The 6-week intervention included a media campaign, public relations,
      and taste tests. Campaign effectiveness was measured using sales data and cross
      sectional telephone surveys. Survey results showed a significant increase in low
      fat milk consumption from 30.2% to 40.8% of milk drinkers (p < .001) with a
      reduced yet sustained increase at 3 months. This translates to approximately
      65,000 people switching to low-fat milk during the campaign with a sustained
      effect of approximately 32,000 people three months postcampaign. Sales data show
      an increase of low-fat milk sales from 32.7% to 39.9%. Results are similar to
      smaller community initiatives, indicating the program is effective in promoting
      population behavior change but may need booster sessions for sustained effects.

PMID- 17200103
TI  - The WORD (wholeness, oneness, righteousness, deliverance): a faith-based weight
      loss program utilizing a community-based participatory research approach.
AB  - Despite multidisciplinary efforts to control the nation's obesity epidemic,
      obesity has persisted as one of the U.S.'s top public health problems,
      particularly among African Americans. Innovative approaches to address obesity
      that are sensitive to the unique issues of African Americans are needed. Thus, a
      faith-based weight-loss intervention using a community-based participatory
      research approach was developed, implemented, and evaluated with a rural African
      American faith community. A two-group, quasi-experimental, delayed intervention
      design was used, with church as the unit of assignment (treatment n=2, control
      n=2) and individual as the unit of observation (treatment n=36, control n=37).
      Weekly small groups led by trained community members met for 8 weeks and
      emphasized healthy nutrition, physical activity, and faith's connection with
      health. The mean weight loss of the treatment group was 3.60+/-0.64 lbs. compared
      to the 0.59+/-0.59-lb loss of the control group.

PMID- 17200104
TI  - Development and validation of a high-throughput screen for inhibitors of SARS CoV
      and its application in screening of a 100,000-compound library.
AB  - The authors have developed a high-throughput screen (HTS) that allows for the
      identification of potential inhibitors of the severe acute respiratory syndrome
      coronavirus (SARS CoV) from large compound libraries. The luminescent-based assay
      measures the inhibition of SARS CoV-induced cytopathic effect (CPE) in Vero E6
      cells. The assay was validated in 96-well plates in a BSL3 containment facility.
      The assay is sensitive and robust, with Z values > 0.6, signal to background
      (S/B) > 16, and signal to noise (S/N) > 3. The assay was further validated with 2
      different diversity sets of compounds against the SARS CoV. The "hit" rate for
      both libraries was approximately 0.01%. The validated HTS assay was then employed
      to screen a 100,000-compound library against SARS CoV. The hit rate for the
      library in a single-dose format was determined to be approximately 0.8%.
      Screening of the 3 libraries resulted in the identification of several novel
      compounds that effectively inhibited the CPE of SARS CoV in vitro-compounds which
      will serve as excellent lead candidates for further evaluation. At a 10-microM
      concentration, 3 compounds with selective indexes (SI50) of > 53 were discovered.

PMID- 17200105
TI  - Proteomics discovery of metalloproteinase substrates in the cellular context by
      iTRAQ labeling reveals a diverse MMP-2 substrate degradome.
AB  - Elucidation of protease substrate degradomes is essential for understanding the
      function of proteolytic pathways in the protease web and how proteases regulate
      cell function. We identified matrix metalloproteinase-2 (MMP-2) cleaved proteins,
      solubilized pericellular matrix, and shed cellular ectodomains in the cellular
      context using a new multiplex proteomics approach. Tryptic peptides of intact and
      cleaved proteins, collected from conditioned culture medium of Mmp2(-/-)
      fibroblasts expressing low levels of transfected active human MMP-2 at different
      time points, were amine-labeled with iTRAQ mass tags. Peptide identification and
      relative quantitation between active and inactive protease transfectants were
      achieved following tag fragmentation during tandem MS. Known substrates of MMP-2
      were identified thereby validating this technique with many novel MMP-2
      substrates including the CX(3)CL1 chemokine fractalkine, osteopontin, galectin-1,
      and HSP90alpha also being identified and biochemically confirmed. In comparison
      with ICAT-labeling and quantitation, 8-9-fold more proteins and substrates were
      identified by iTRAQ. "Peptide mapping," the location of multiple peptides
      identified within a particular protein by iTRAQ in combination with their
      relative abundance ratios, enabled the domain shed and general location of the
      cleavage site to be identified in the native cellular substrate. Hence this
      advance in degradomics cell-based screens for native protein substrates casts new
      light on the roles for proteases in cell function.

PMID- 17200106
TI  - Toward a comprehensive atlas of the physical interactome of Saccharomyces
      cerevisiae.
AB  - Defining protein complexes is critical to virtually all aspects of cell biology.
      Two recent affinity purification/mass spectrometry studies in Saccharomyces
      cerevisiae have vastly increased the available protein interaction data. The
      practical utility of such high throughput interaction sets, however, is
      substantially decreased by the presence of false positives. Here we created a
      novel probabilistic metric that takes advantage of the high density of these
      data, including both the presence and absence of individual associations, to
      provide a measure of the relative confidence of each potential protein-protein
      interaction. This analysis largely overcomes the noise inherent in high
      throughput immunoprecipitation experiments. For example, of the 12,122 binary
      interactions in the general repository of interaction data (BioGRID) derived from
      these two studies, we marked 7504 as being of substantially lower confidence.
      Additionally, applying our metric and a stringent cutoff we identified a set of
      9074 interactions (including 4456 that were not among the 12,122 interactions)
      with accuracy comparable to that of conventional small scale methodologies.
      Finally we organized proteins into coherent multisubunit complexes using
      hierarchical clustering. This work thus provides a highly accurate physical
      interaction map of yeast in a format that is readily accessible to the biological
      community.

PMID- 17200107
TI  - Elucidation, quantitative refinement, and in vivo utilization of the HOXA13 DNA
      binding site.
AB  - Mutations in Hoxa13 cause malformations of the appendicular skeleton and
      genitourinary tract, including digit loss, syndactyly, and hypospadias. To
      determine the molecular basis for these defects, the DNA sequences bound by
      HOXA13 were empirically determined, revealing a novel high affinity binding site.
      Correlating the utilization of this high affinity binding site with genes
      exhibiting perturbed expression in Hoxa13 mutant limbs, we identified that HOXA13
      suppresses the expression of the BMP antagonist, Sostdc1. In the absence of
      HOXA13 function, Sostdc1 is ectopically expressed in the distal limb, causing
      reduced expression of BMP-activated genes and decreased SMAD phosphorylation.
      Limb chromatin immunoprecipitation revealed HOXA13 binding at its high affinity
      site in two conserved Sostdc1 regulatory sites in vivo. In vitro, HOXA13
      represses gene expression through the Sostdc1 high affinity binding sites in a
      dosage-dependent manner. Together, these findings confirm that the high affinity
      HOXA13 binding site deduced by quantitative analyses is used in vivo to
      facilitate HOXA13 target gene regulation, providing a critical advance toward
      understanding the molecular basis for defects associated with the loss of HOXA13
      function.

PMID- 17200109
TI  - Redox sensitivity of the ryanodine receptor interaction with FK506-binding
      protein.
AB  - The ryanodine receptor (RyR) calcium release channel functions as a redox sensor
      that is sensitive to channel modulators. The FK506-binding protein (FKBP) is an
      important regulator of channel activity, and disruption of the RyR2-FKBP12.6
      association has been implicated in cardiac disease. In the present study, we
      investigated whether the RyR-FKBP association is redox-regulated. Using co
      immunoprecipitation assays of solubilized native RyR2 from cardiac muscle
      sarcoplasmic reticulum (SR) with recombinant [(35)S]FKBP12.6, we found that the
      sulfydryl-oxidizing agents, H(2)O(2) and diamide, result in diminished RyR2
      FKBP12.6 binding. Co-sedimentation experiments of cardiac SR vesicles with
      [(35)S]FKBP12.6 also demonstrated that oxidizing reagents decreased FKBP binding.
      Matching results were obtained with skeletal muscle SR. Notably, H(2)O(2) and
      diamide differentially affected the RyR2-FKBP12.6 interaction, decreasing binding
      to approximately 75 and approximately 50% of control, respectively. In addition,
      the effect of H(2)O(2) was negligible when the channel was in its closed state or
      when applied after FKBP binding had occurred, whereas diamide was always
      effective. A cysteine-null mutant FKBP12.6 retained redox-sensitive interaction
      with RyR2, suggesting that the effect of the redox reagents is exclusively via
      sites on the ryanodine receptor. K201 (or JTV519), a drug that has been proposed
      to prevent FKBP12.6 dissociation from the RyR2 channel complex, did not restore
      normal FKBP binding under oxidizing conditions. Our results indicate that the
      redox state of the RyR is intimately connected with FKBP binding affinity.

PMID- 17200108
TI  - The dihydrolipoamide acetyltransferase is a novel metabolic longevity factor and
      is required for calorie restriction-mediated life span extension.
AB  - Calorie restriction (CR) extends life span in a wide variety of species. Recent
      studies suggest that an increase in mitochondrial metabolism mediates CR-induced
      life span extension. Here we present evidence that Lat1 (dihydrolipoamide
      acetyltransferase), the E2 component of the mitochondrial pyruvate dehydrogenase
      complex, is a novel metabolic longevity factor in the CR pathway. Deleting the
      LAT1 gene abolishes life span extension induced by CR. Overexpressing Lat1
      extends life span, and this life span extension is not further increased by CR.
      Similar to CR, life span extension by Lat1 overexpression largely requires
      mitochondrial respiration, indicating that mitochondrial metabolism plays an
      important role in CR. Interestingly, Lat1 overexpression does not require the
      Sir2 family to extend life span, suggesting that Lat1 mediates a branch of the CR
      pathway that functions in parallel to the Sir2 family. Lat1 is also a limiting
      longevity factor in nondividing cells in that overexpressing Lat1 extends cell
      survival during prolonged culture at stationary phase. Our studies suggest that
      Lat1 overexpression extends life span by increasing metabolic fitness of the
      cell. CR may therefore also extend life span and ameliorate age-associated
      diseases by increasing metabolic fitness through regulating central metabolic
      enzymes.

PMID- 17200110
TI  - Keratinocyte growth factor/fibroblast growth factor-7-regulated cell migration
      and invasion through activation of NF-kappaB transcription factors.
AB  - Keratinocyte growth factor (KGF)/fibroblast growth factor-7 (FGF-7) is a
      paracrine- and epithelium-specific growth factor produced by cells of mesenchymal
      origin. It acts exclusively through FGF-7 receptor (FGFR2/IIIb), which is
      expressed predominantly by epithelial cells, but not by fibroblasts, suggesting
      that it might function as a paracrine mediator of mesenchymal-epithelial
      interactions. KGF/FGF-7 plays an essential role in the growth of epithelial cells
      and is frequently overexpressed in cancers of epithelial origin such as
      pancreatic cancer, switching paracrine stimulation of KGF/FGF-7 to an autocrine
      loop. Less is known, however, about the signaling pathways by which KGF/FGF-7
      regulates the response of epithelial cells. To delineate the signaling pathways
      activated by KGF/FGF-7 and examine cellular response to KGF/FGF-7 stimulation, we
      performed functional analysis of KGF/FGF-7 action. In this report, we show that
      KGF/FGF-7 activated nuclear factor kappaB (NF-kappaB), which in turn induced
      expression of VEGF, MMP-9, and urokinase-type plasminogen activator and increased
      migration and invasion of KGF/FGF-7-stimulated human pancreatic ductal epithelial
      cells. Expression of phosphorylation-defective IkappaBalpha
      (IkappaBalphaS32A,S36A), which blocked NF-kappaB activation, inhibited KGF/FGF-7
      induced gene expression and cell migration and invasion. Our results demonstrate
      for the first time that KGF/FGF-7 induces NF-kappaB activation and that NF-kappaB
      plays an essential role in regulation of KGF/FGF-7-inducible gene expression and
      KGF/FGF-7-initiated cellular responses. Thus, these findings identify one
      signaling pathway for KGF/FGF-7-regulated cell migration and invasion and suggest
      that paracrine sources of KGF/FGF-7 are one of the malignancy-contributing
      factors from tumor stroma.

PMID- 17200111
TI  - Combined simulation and mutagenesis analyses reveal the involvement of key
      residues for peroxisome proliferator-activated receptor alpha helix 12 dynamic
      behavior.
AB  - The dynamic properties of helix 12 in the ligand binding domain of nuclear
      receptors are a major determinant of AF-2 domain activity. We investigated the
      molecular and structural basis of helix 12 mobility, as well as the involvement
      of individual residues with regard to peroxisome proliferator-activated receptor
      alpha (PPARalpha) constitutive and ligand-dependent transcriptional activity.
      Functional assays of the activity of PPARalpha helix 12 mutants were combined
      with free energy molecular dynamics simulations. The agreement between the
      results from these approaches allows us to make robust claims concerning the
      mechanisms that govern helix 12 functions. Our data support a model in which
      PPARalpha helix 12 transiently adopts a relatively stable active conformation
      even in the absence of a ligand. This conformation provides the interface for the
      recruitment of a coactivator and results in constitutive activity. The receptor
      agonists stabilize this conformation and increase PPARalpha transcription
      activation potential. Finally, we disclose important functions of residues in
      PPARalpha AF-2, which determine the positioning of helix 12 in the active
      conformation in the absence of a ligand. Substitution of these residues
      suppresses PPARalpha constitutive activity, without changing PPARalpha ligand
      dependent activation potential.

PMID- 17200112
TI  - Engineering the substrate specificity of Staphylococcus aureus Sortase A. The
      beta6/beta7 loop from SrtB confers NPQTN recognition to SrtA.
AB  - The Staphylococcus aureus transpeptidase Sortase A (SrtA) anchors virulence and
      colonization-associated surface proteins to the cell wall. SrtA selectively
      recognizes a C-terminal LPXTG motif, whereas the related transpeptidase Sortase B
      (SrtB) recognizes a C-terminal NPQTN motif. In both enzymes, cleavage occurs
      after the conserved threonine, followed by amide bond formation between threonine
      and the pentaglycine cross-bridge of cell wall peptidoglycan. Genetic and
      biochemical studies strongly suggest that SrtA and SrtB exhibit exquisite
      specificity for their recognition motifs. To better understand the origins of
      substrate specificity within these two isoforms, we used sequence and structural
      analysis to predict residues and domains likely to be involved in conferring
      substrate specificity. Mutational analyses and domain swapping experiments were
      conducted to test their function in substrate recognition and specificity. Marked
      changes in the specificity profile of SrtA were obtained by replacing the
      beta6/beta7 loop in SrtA with the corresponding domain from SrtB. The chimeric
      beta6/beta7 loop swap enzyme (SrtLS) conferred the ability to acylate NPQTN
      containing substrates, with a k(cat)/K(m)(app) of 0.0062 +/- 0.003 m(-1) s(-1).
      This enzyme was unable to perform the transpeptidation stage of the reaction,
      suggesting that additional domains are required for transpeptidation to occur.
      The overall catalytic specificity profile
      (k(cat)/K(m)(app)(NPQTN)/k(cat)/K(m)(app)(LPETG)) of SrtLS was altered 700,000
      fold from SrtA. These results indicate that the beta6/beta7 loop is an important
      site for substrate recognition in sortases.

PMID- 17200113
TI  - Multiple sequential steps involved in the binding of inhibitors to cytochrome
      P450 3A4.
AB  - Cytochrome P450 (P450) 3A4 is an extensively studied human enzyme involved in the
      metabolism of >50% of drugs. The mechanism of the observed homotropic and
      heterotropic cooperativity in P450 3A4-catalyzed oxidations is not well
      understood, and together with the cooperative behavior, a detailed understanding
      of interaction of drug inhibitors with P450 3A4 is important in predicting
      clinical drug-drug interactions. The interactions of P450 3A4 with several
      structurally diverse inhibitors were investigated using both kinetic and
      thermodynamic approaches to resolve the steps involved in binding of these
      ligands. The results of pre-steady-state absorbance and fluorescence experiments
      demonstrate that inhibitor binding is clearly a multistep process, even more
      complex than the binding of substrates. Based on spectrophotometric equilibrium
      binding titrations as well as isothermal titration calorimetry experiments, the
      stoichiometry of binding appears to be 1:1 in the concentration ranges studied.
      Using a sequential-mixing stopped-flow approach, we were also able to show that
      the observed multiphasic binding kinetics is the result of sequential events as
      opposed to the existence of multiple enzyme populations in dynamic equilibrium
      that interact with ligands at different rates. We propose a three-step minimal
      model for inhibitor binding, developed with kinetic simulations, consistent with
      our previously reported model for the binding of substrates, although it is
      possible that even more steps are involved.

PMID- 17200114
TI  - Protease-activating receptor-4 induces full platelet spreading on a fibrinogen
      matrix: involvement of ERK2 and p38 and Ca2+ mobilization.
AB  - Although the involvement of protease-activating receptor PAR1 and PAR4 is well
      established in platelet aggregation, their role in platelet adhesion and
      spreading has yet to be characterized. We investigated platelet adhesion and
      spreading on a fibrinogen matrix after PAR1 and PAR4 stimulation in correlation
      with the activation of two MAPKs, ERK2 and p38. Of the two PAR-activating
      peptides (PAR-APs), PAR1-AP and PAR4-AP, which both induce adhesion, only PAR4-AP
      induced full platelet spreading. Although both PAR1-AP and PAR4-AP induced ADP
      secretion, which is required for platelet spreading, only PAR4-AP induced
      sustained Ca(2+) mobilization. In these conditions of PAR4 induction, ERK2 and
      p38 activation were involved in platelet spreading but not in platelet adhesion.
      p38 phosphorylation was dependent on ADP signaling through P2Y12, its receptor.
      ERK2 phosphorylation was triggered through integrin alphaIIbbeta3 outside-in
      signaling and was dependent on the Rho pathway. ERK2 and p38 activation induced
      phosphorylation of the myosin light chain and actin polymerization, respectively,
      necessary for cytoskeleton reorganization. These findings provide the first
      evidence that thrombin requires PAR4 for the full spreading response. ERK2 and
      p38 and sustained Ca(2+) mobilization, involved in PAR4-induced platelet
      spreading, contribute to the stabilization of platelet thrombi at sites of high
      thrombin production.

PMID- 17200115
TI  - Inhibition of B56-containing protein phosphatase 2As by the early response gene
      IEX-1 leads to control of Akt activity.
AB  - The importance of PP2A in the regulation of Akt/PKB activity has long been
      recognized but the nature of the holoenzyme involved and the mechanisms
      controlling dephosphorylation are not yet known. We identified IEX-1, an early
      gene product with proliferative and survival activities, as a specific inhibitor
      of B56 regulatory subunit-containing PP2A. IEX-1 inhibits B56-PP2A activity by
      allowing the phosphorylation of B56 by ERK. This leads to sustained ERK
      activation. IEX-1 has no effect on PP2A containing other B family subunits. Thus,
      studying IEX-1 contribution to signaling should help the discovery of new
      pathways controlled by B56-PP2A. By using overexpression and RNA interference, we
      show here that IEX-1 increases Akt/PKB activity in response to various growth
      factors by preventing Akt dephosphorylation on both Thr(308) and Ser(473)
      residues. PP2A-B56beta and gamma subunits have the opposite effect and reverse
      IEX-1-mediated Akt activation. The effect of IEX-1 on Akt is ERK-dependent.
      Indeed: (i) a IEX-1 mutant deficient in ERK binding had no effect on Akt; (ii)
      ERK dominant-negative mutants reduced IEX-1-mediated increase in pAkt; (iii) a
      B56beta mutant that cannot be phosphorylated in the ERK.IEX-1 complex showed an
      enhanced ability to compete with IEX-1. These results identify B56-containing
      PP2A holoenzymes as Akt phosphatases. They suggest that IEX-1 behaves as a
      general inhibitor of B56 activity, enabling the control of both ERK and Akt
      signaling downstream of ERK.

PMID- 17200117
TI  - Src docks to A-kinase anchoring protein gravin, regulating beta2-adrenergic
      receptor resensitization and recycling.
AB  - Gravin (AKAP12) is a membrane-associated scaffold that provides docking for
      protein kinases, phosphatases, and adaptor molecules obligate for resensitization
      and recycling of beta(2)-adrenergic receptors. Gravin binds to the cell membrane
      in a Ca(2+)-sensitive manner and to receptors through well characterized protein
      protein interactions. Although the interaction of serine/threonine, cyclic AMP
      dependent protein kinase with protein kinase A-anchoring proteins is well
      described and involves a kinase regulatory subunit binding domain in the C
      terminus of these proteins, far less is known about tyrosine kinase docking to
      members of this family of scaffolds. The non-receptor tyrosine kinase Src
      regulates resensitization of beta(2)-adrenergic receptors and docks to gravin.
      Gravin displays nine proline-rich domains distributed throughout the molecule.
      One class I ligand for Src homology domain 3 docking, found in the N terminus
      ((10)RXPXXP(15)) of gravin, is shown to bind Src. Binding of Src to gravin
      activates the intrinsic tyrosine kinase of Src. Mutagenesis/deletion of the class
      I ligand (P15A,P16A) on the N terminus of gravin abolishes both the docking of
      Src to gravin as well as the receptor resensitization and recycling catalyzed by
      gravin. The Src-binding peptide-(1-51) of gravin behaves as a dominant-negative
      for AKAP gravin regulation of receptor resensitization/recycling. The tyrosine
      kinase Src plays an essential role in the AKAP gravin-mediated receptor
      resensitization and recycling, an essential aspect of receptor biology.

PMID- 17200116
TI  - Expression of the calcium-binding protein S100A4 is markedly up-regulated by
      osmotic stress and is involved in the renal osmoadaptive response.
AB  - Proteomic analysis of Inner Medullary Collecting Duct (IMCD3) cells adapted to
      increasing levels of tonicity (300, 600, and 900 mosmol/kg H(2)O) by two
      dimensional difference gel electrophoresis and mass spectrometry revealed several
      proteins as yet unknown to be up-regulated in response to hypertonic stress. Of
      these proteins, one of the most robustly up-regulated (22-fold) was S100A4. The
      identity of the protein was verified by high pressure liquid chromatography-mass
      spectrometry. Western blot analysis confirmed increased expression with increased
      tonicity, both acute and chronic. S100A4 protein expression was further confirmed
      by immunocytochemical analysis. Cells grown in isotonic conditions showed
      complete absence of immunostaining, whereas chronically adapted IMCD3 cells had
      uniform cytoplasmic localization. The protein is also regulated in vivo as in
      mouse kidney tissues S100A4 expression was many -fold greater in the papilla as
      compared with the cortex and increased further in the papilla upon 36 h of
      thirsting. Increased expression of S100A4 was also observed in the medulla and
      papilla, but not the cortex of a human kidney. Data from Affymetrix gene chip
      analysis and quantitative PCR also revealed increased S100A4 message in IMCD3
      cells adapted to hypertonicity. The initial expression of message increased at 8
      10 h following exposure to acute sublethal hypertonic stress (550 mosmol/kg
      H(2)O). Protein and message half-life in IMCD3 cells were 85.5 and 6.8 h,
      respectively. Increasing medium tonicity with NaCl, sucrose, mannitol, and
      choline chloride stimulated S100A4 expression, whereas urea did not. Silencing of
      S100A4 expression using a stable siRNA vector (pSM2; Open Biosystems) resulted in
      a 48-h delay in adaptation of IMCD3 cells under sublethal osmotic stress,
      suggesting S100A4 is involved in the osmoadaptive response. In summary, we
      describe the heretofore unrecognized up-regulation of a small calcium-binding
      protein, both in vitro and in vivo, whose absence profoundly delays
      osmoadaptation and slows cellular growth under hypertonic conditions.

PMID- 17200119
TI  - The local phospholipid environment modulates the activation of blood clotting.
AB  - Examples abound of membrane-bound enzymes for which the local membrane
      environment plays an important role, including the ectoenzyme that triggers blood
      clotting, the plasma serine protease, factor VIIa, bound to the integral membrane
      protein, tissue factor. The activity of this enzyme complex is markedly
      influenced by lipid bilayer composition and further by tissue factor partitioning
      into membrane microdomains on some cell surfaces. Unfortunately, little is known
      about how membrane microdomain composition controls factor VIIa-tissue factor
      activity, as reactions catalyzed by membrane-tethered enzymes are typically
      studied under conditions in which the experimenter cannot control the composition
      of the membrane in the immediate vicinity of the enzyme. To overcome this
      problem, we used a nanoscale approach that afforded complete control over the
      membrane environment surrounding tissue factor by assembling the factor
      VIIa.tissue factor complex on stable bilayers containing 67 +/- 1 phospholipid
      molecules/leaflet (Nanodiscs). We investigated how local changes in phospholipid
      bilayer composition modulate the activity of the factor VIIa.tissue factor
      complex. We also addressed whether this enzyme requires a pool of membrane-bound
      protein substrate (factor X) for efficient catalysis, or alternatively if it
      could efficiently activate factor X, which binds directly to the membrane
      nanodomain adjacent to tissue factor. We have shown that full proteolytic
      activity of the factor VIIa.tissue factor complex requires extremely high local
      concentrations of anionic phospholipids and further that a large pool of membrane
      bound factor X is not required to support sustained catalysis.

PMID- 17200118
TI  - Oxidoreductase interactions include a role for ERp72 engagement with mutant
      thyroglobulin from the rdw/rdw rat dwarf.
AB  - Newly synthesized thyroglobulin (Tg), the secretory glycoprotein that serves as
      precursor in thyroid hormone synthesis, normally forms transient covalent protein
      complexes with oxidoreductases of the endoplasmic reticulum (ER). The Tg-G2320R
      mutation is responsible for congenital hypothyroidism in rdw/rdw rats, in which a
      lack of secondary thyroid enlargement (goiter) implicates death of thyrocytes as
      part of disease pathogenesis. We found that mutant Tg-G2320R was retained within
      the ER with no detectable synthesis of thyroxine, had persistent exposure of free
      cysteine thiols, and was associated with activated ER stress response but
      incomplete ER-associated degradation (ERAD). Tg-G2320R associated with multiple
      ER resident proteins, most notably ERp72, including covalent Tg-ERp72
      interactions. In PC Cl3 thyrocytes, inducible overexpression of ERp72 increased
      the ability of cells to maintain Tg cysteines in a reduced state. Noncovalent
      interactions of several ER chaperones with newly synthesized Tg-G2320R diminished
      over time in parallel with ERAD of the mutant protein, yet a small ERAD-resistant
      Tg fraction remained engaged in covalent association with ERp72 even 2 days post
      synthesis. Such covalent protein aggregates may set the stage for apoptotic
      thyrocyte cell death, preventing thyroid goiter formation in rdw/rdw rats.

PMID- 17200120
TI  - PU.1, interferon regulatory factor (IRF) 2, and the interferon consensus sequence
      binding protein (ICSBP/IRF8) cooperate to activate NF1 transcription in
      differentiating myeloid cells.
AB  - Nf1 (neurofibromin 1) is a Ras-GAP protein that regulates cytokine-induced
      proliferation of myeloid cells. In previous studies, we found that the interferon
      consensus sequence-binding protein (ICSBP; also referred to as interferon
      regulatory factor 8) activates transcription of the gene encoding Nf1 (the NF1
      gene) in differentiating myeloid cells. We also found that NF1 activation
      requires cytokine-stimulated phosphorylation of a conserved tyrosine residue in
      the interferon regulatory factor (IRF) domain of ICSBP/IRF8. In this study, we
      found that ICSBP/IRF8 cooperates with PU.1 and interferon regulatory factor 2 to
      activate a composite ets/IRF-cis element in the NF1 promoter. We found that PU.1
      binds directly to the NF1-cis element, and DNA-bound PU.1 interacts with IRF2,
      recruiting IRF2 to the cis element. This interaction requires cytokine-induced
      phosphorylation of specific serine residues in the PU.1 PEST domain and of a
      conserved tyrosine residue in the IRF domain of IRF2. We found that ICSBP/IRF8
      interaction with the NF1-cis element requires pre-binding of PU.1 and IRF2. The
      conserved IRF domain tyrosine in ICSBP/IRF8 is required for interaction with the
      DNA-bound PU.1-IRF2 heterodimer. NF1 deficiency in myeloid progenitor cells
      results in cytokine hypersensitivity and myeloproliferation. Therefore, these
      studies identify a target gene for the previously observed tumor-suppressor
      effect of PU.1. Additionally, these studies identify a tumor-suppressor function
      for the "oncogenic" transcription factor, IRF2.

PMID- 17200121
TI  - Dynamic modification of a mutant cytoplasmic cysteine residue modulates the
      conductance of the human 5-HT3A receptor.
AB  - Structural models suggest that Arg(436) lies within five cytoplasmic portals of
      the 5-HT(3A) receptor. We tested both the accessibility of residue 436 and the
      influence of its charge on single channel conductance (gamma) by substituting
      Arg(436) with Cys and examining the effect of methanethiosulfonate (MTS) reagents
      on gamma. Inclusion of positively charged 2-aminoethyl-MTS (MTSEA) within the
      electrode solution reduced gamma of 5-HT(3A)(R436C) receptors in outside-out
      patches from 7.8 +/- 0.5 to 5.0 +/- 0.5 picosiemens (pS). To increase gamma, we
      substituted Arg(436) by Cys in the 5-HT(3A)(R432Q,R440A) mutant, yielding the 5
      HT(3A)(QCA) construct with a gamma of 17.7 +/- 0.4 pS. Modification of 5
      HT(3A)(QCA) receptors by MTSEA or 2-(trimethylammonium) ethyl-MTS reduced gamma
      to 8.7 +/- 0.5 and 6.7 +/- 0.4 pS, respectively, both significantly below that of
      channels exposed to nonpolar propyl-MTS. Extracellular MTSEA, but not 2
      (trimethylammonium) ethyl-MTS, crossed the membrane and in so doing slowly (tau =
      94 s) reduced gamma. MTSEA more rapidly (tau = 15 s) reduced the gamma of 5
      HT(3A)(QCA) receptors in inside-out patches, an effect reversed by the reducing
      agent dithiothreitol. Cys(436) modification by negatively charged 2-carboxyethyl
      MTS and 2-sulfonatoethyl-MTS increasedgamma to 23 +/- 1.0 and 26 +/- 0.7 pS,
      respectively. MTS reagents did not affect gamma values for 5-HT(3A)(QDA)
      constructs with Cys substituted for Lys(431) predicted to be outside the entrance
      to the portals. Collectively, the data demonstrate that the dynamic modification
      of the charge of a cytoplasmic residue regulates gamma, consistent with the
      existence of cytoplasmic portals that impose a rate-limiting barrier to ion
      conduction in Cys loop receptors.

PMID- 17200122
TI  - Oxysterols are novel activators of the hedgehog signaling pathway in pluripotent
      mesenchymal cells.
AB  - Pluripotent mesenchymal cells form a population of precursors to a variety of
      cell types, including osteoblasts and adipocytes. Aging tilts the balance in
      favor of adipocyte differentiation at the expense of osteoblast differentiation,
      resulting in reduced bone formation and osteopenic disorders, including
      osteoporosis, in humans and animals. Understanding the mechanisms involved in
      causing this apparent shift in differentiation and identifying factors that
      stimulate osteoblast formation while inhibiting adipogenesis are of great
      therapeutic interest. In this study we report that specific, naturally occurring
      oxysterols, previously shown to direct pluripotent mesenchymal cells toward an
      osteoblast lineage, exert their osteoinductive effects through activation of
      Hedgehog signaling pathway. This was demonstrated by 1) oxysterol-induced
      expression of the Hh target genes Gli-1 and Patched, 2) oxysterol-induced
      activation of a luciferase reporter driven by a multimerized Gli-responsive
      element, 3) inhibition of oxysterol effects by the hedgehog pathway inhibitor,
      cyclopamine, and 4) unresponsiveness of Smoothened-/- mouse embryonic fibroblasts
      to oxysterols. Using Patched-/- cells that possess high baseline Gli activity, we
      found that oxysterols did not dramatically shift the IC50 concentration of
      cyclopamine needed to inhibit Gli activity in these cells. Furthermore, binding
      studies showed that oxysterols did not compete with fluorescently labeled
      cyclopamine, BODIPY-cyclopamine, for direct binding to Smoothened. These findings
      demonstrate that oxysterols stimulate hedgehog pathway activity by indirectly
      activating the seven-transmembrane pathway component Smoothened. Osteoinductive
      oxysterols are, therefore, novel activators of the hedgehog pathway in
      pluripotent mesenchymal cells, and they may be important modulators of this
      critical signaling pathway that regulates numerous developmental and post
      developmental processes.

PMID- 17200123
TI  - NAD(P)H oxidases regulate HIF-2alpha protein expression.
AB  - Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is
      linked to the development of hereditary and sporadic renal cell carcinoma (RCC).
      In the absence of VHL, the alpha subunits of heterodimeric hypoxia-inducible
      transcription factors (HIF-1alpha and HIF-2alpha) are stabilized. Reactive oxygen
      species, generated by NAD(P)H oxidases, are involved in signaling cascades of
      malignant growth. We show that in VHL-deficient cells p22phox, Nox4 protein
      levels and NADPH-dependent superoxide generation are increased. Reintroduction of
      VHL into the VHL-deficient cells down-regulates the expression of p22phox and
      NADPH-dependent superoxide generation. Inhibition of the 26 S proteasome in VHL
      expressing cells increased p22phox protein levels, which correlated with an
      increase of NADPH-dependent superoxide generation. We also show that p22phox co
      immunoprecipitates with VHL in vivo. Moreover, p22phox is a target of
      ubiquitination. Importantly, in VHL-deficient cells, diphenyleneiodonium chloride
      (DPI), an inhibitor of Nox oxidases, decreased the expression of HIF-2alpha. Down
      regulation of Nox1, Nox4, and p22phox expression by small interfering RNA also
      decreased HIF-2alpha protein expression and inhibited Akt and 4E-BP1
      phosphorylation, suggesting that a translational mechanism is involved in
      maintaining HIF-2alpha in VHL-deficient cells. Colony formation by RCC 786-O in
      soft agar was markedly inhibited by DPI. Moreover, DPI significantly inhibited
      RCC 786-O tumor formation in athymic mice. Collectively, the data demonstrate
      that VHL protein exerts its tumor suppressor action, at least partially, via
      inhibition of p22phox-based Nox4/Nox1 NADPH oxidase-dependent reactive oxygen
      species generation.

PMID- 17200124
TI  - Prevention of peroxynitrite-induced apoptosis of motor neurons and PC12 cells by
      tyrosine-containing peptides.
AB  - Although peroxynitrite stimulates apoptosis in many cell types, whether
      peroxynitrite acts directly as an oxidant or the induction of apoptosis is
      because of the radicals derived from peroxynitrite decomposition remains unknown.
      Before undergoing apoptosis because of trophic factor deprivation, primary motor
      neuron cultures become immunoreactive for nitrotyrosine. We show here using
      tyrosine-containing peptides that free radical processes mediated by
      peroxynitrite decomposition products were required for triggering apoptosis in
      primary motor neurons and in PC12 cells cultures. The same concentrations of
      tyrosine-containing peptides required to prevent the nitration and apoptosis of
      motor neurons induced by trophic factor deprivation and of PC12 cells induced by
      peroxynitrite also prevented peroxynitrite-mediated nitration of motor neurons,
      brain homogenates, and PC12 cells. The heat shock protein 90 chaperone was
      nitrated in both trophic factor-deprived motor neurons and PC12 cells incubated
      with peroxynitrite. Tyrosine-containing peptides did not affect the induction of
      PC12 cell death by hydrogen peroxide. Tyrosine-containing peptides should protect
      by scavenging peroxynitrite-derived radicals and not by direct reactions with
      peroxynitrite as they neither increase the rate of peroxynitrite decomposition
      nor decrease the bimolecular peroxynitrite-mediated oxidation of thiols. These
      results reveal an important role for free radical-mediated nitration of tyrosine
      residues, in apoptosis induced by endogenously produced and exogenously added
      peroxynitrite; moreover, tyrosine-containing peptides may offer a novel strategy
      to neutralize the toxic effects of peroxynitrite.

PMID- 17200125
TI  - Roles of bound quinone in the single subunit NADH-quinone oxidoreductase (Ndi1)
      from Saccharomyces cerevisiae.
AB  - To understand the biochemical basis for the function of the rotenone-insensitive
      internal NADH-quinone (Q) oxidoreductase (Ndi1), we have overexpressed mature
      Ndi1 in Escherichia coli membranes. The Ndi1 purified from the membranes
      contained one FAD and showed enzymatic activities comparable with the original
      Ndi1 isolated from Saccharomyces cerevisiae. When extracted with Triton X-100,
      the isolated Ndi1 did not contain Q. The Q-bound form was easily reconstituted by
      incubation of the Q-free Ndi1 enzyme with ubiquinone-6. We compared the
      properties of Q-bound Ndi1 enzyme with those of Q-free Ndi1 enzyme, with higher
      activity found in the Q-bound enzyme. Although both are inhibited by low
      concentrations of AC0-11 (IC(50) = 0.2 microm), the inhibitory mode of AC0-11 on
      Q-bound Ndi1 was distinct from that of Q-free Ndi1. The bound Q was slowly
      released from Ndi1 by treatment with NADH or dithionite under anaerobic
      conditions. This release of Q was prevented when Ndi1 was kept in the reduced
      state by NADH. When Ndi1 was incorporated into bovine heart submitochondrial
      particles, the Q-bound form, but not the Q-free form, established the NADH-linked
      respiratory activity, which was insensitive to piericidin A but inhibited by KCN.
      Furthermore, Ndi1 produces H(2)O(2) as isolated regardless of the presence of
      bound Q, and this H(2)O(2) was eliminated when the Q-bound Ndi1, but not the Q
      free Ndi1, was incorporated into submitochondrial particles. The data suggest
      that Ndi1 bears at least two distinct Q sites: one for bound Q and the other for
      catalytic Q.

PMID- 17200126
TI  - Rapid turnover of mcl-1 couples translation to cell survival and apoptosis.
AB  - Inhibition of translation plays a role in apoptosis induced by a variety of
      stimuli, but the mechanism by which it promotes apoptosis has not been
      established. We have investigated the hypothesis that selective degradation of
      anti-apoptotic regulatory protein(s) is responsible for apoptosis resulting from
      translation inhibition. Induction of apoptosis by cycloheximide was detected
      within 2-4 h and blocked by proteasome inhibitors, indicating that degradation of
      short-lived protein(s) was required. Caspase inhibition and overexpression of Bcl
      x(L) blocked cycloheximide-induced apoptosis. In addition, cycloheximide induced
      rapid activation of Bak and Bax, which required proteasome activity. Mcl-1 was
      degraded by the proteasome with a half-life of approximately 30 min following
      inhibition of protein synthesis, preceding Bak/Bax activation and the onset of
      apoptosis. Overexpression of Mcl-1 blocked apoptosis induced by cycloheximide,
      whereas RNA interference knockdown of Mcl-1 induced apoptosis. Knockdown of Bim
      and Bak, downstream targets of Mcl-1, inhibited cycloheximide-induced apoptosis,
      as did knockdown of Bax. Apoptosis resulting from inhibition of translation thus
      involves the rapid degradation of Mcl-1, leading to activation of Bim, Bak, and
      Bax. Because of its rapid turnover, Mcl-1 may serve as a convergence point for
      signals that affect global translation, coupling translation to cell survival and
      the apoptotic machinery.

PMID- 17200128
TI  - Work-related asthma symptoms and attitudes to the workplace.
AB  - BACKGROUND: The Health & Safety Executive estimate that between 1500-3000 UK
      workers develop asthma through potentially avoidable workplace exposures each
      year. AIMS: To assess the perception of health, safety and the work environment
      by workers with symptoms suggestive of occupational asthma. METHODS: A total of
      97 workers referred to hospital specialists with symptoms suggestive of
      occupational asthma were studied in order to investigate their attitudes to the
      workplace, safety and health. A qualitative study design using semi-structured
      telephone interviews at 2 months and 12 months following enrolment was used at 6
      national UK centres with a special interest in occupational asthma. RESULTS: Many
      workers in the study felt let down by the workplace and management and perceived
      that a lack of health and safety measures had contributed to the development of
      their asthma symptoms. Many workers felt that their employers were 'uncaring' and
      were pursuing or considering medico-legal cases against them. CONCLUSIONS:
      Workers' perception of risk influences their behaviour in the workplace, and
      their own health beliefs potentially create barriers to changing this. It is
      essential to consider workers' perceptions when developing strategies to effect
      change within the workplace.

PMID- 17200127
TI  - Functional disorders: a cause of increasing work absence?

PMID- 17200129
TI  - Why I became an occupational physician...

PMID- 17200130
TI  - A man with four coronary arteries.

PMID- 17200131
TI  - Mutation scanning the GJB1 gene with high-resolution melting analysis:
      implications for mutation scanning of genes for Charcot-Marie-Tooth disease.
AB  - BACKGROUND: X-linked Charcot-Marie-Tooth type 1 disease has been associated with
      280 mutations in the GJB1 [gap junction protein, beta 1, 32 kDa (connexin 32,
      Charcot-Marie-Tooth neuropathy, X-linked)] gene. High-resolution melting analysis
      with an automated instrument can be used to scan DNA for alterations, but its use
      in X-linked disorders has not been described. METHODS: A 96-well LightScanner for
      high resolution melting analysis was used to scan amplicons of the GJB1 gene. All
      mutations reported in this study had been confirmed previously by sequence
      analysis. DNA samples were amplified with the double-stranded DNA-binding dye LC
      Green Plus. Melting curves were analyzed as fluorescence difference plots. The
      shift and curve shapes of melting profiles were used to distinguish controls from
      patient samples. RESULTS: The method detected each of the 23 mutations used in
      this study. Eighteen known mutations provided validation of the high-resolution
      melting method and a further 5 mutations were identified in a blind study.
      Altered fluorescence difference curves for all the mutations were easily
      distinguished from the wild-type melting profile. CONCLUSION: High-resolution
      melting analysis is a simple, sensitive, and cost-efficient alternative method to
      scan for gene mutations in the GJB1 gene. The technology has the potential to
      reduce sequencing burden and would be suitable for mutation screening of exons of
      large multiexon genes that have been discovered to be associated with Charcot
      Marie Tooth neuropathy.

PMID- 17200132
TI  - Is supine rest necessary before blood sampling for plasma metanephrines?
AB  - BACKGROUND: The impact of blood sampling in sitting vs supine positions on
      measurements of plasma metanephrines for diagnosis of pheochromocytoma is
      unknown. METHODS: We compared plasma concentrations of free metanephrines in
      samples from patients with primary hypertension obtained after supine rest with
      those obtained in the sitting position without preceding rest. We also assessed
      the effects on diagnostic test performance retrospectively in patients with and
      without pheochromocytoma, and we calculated cost-effectiveness for
      pheochromocytoma testing. RESULTS: Upper reference limits of plasma free
      metanephrines were higher in samples obtained from seated patients without
      preceding rest than from supine patients with preceding rest. Application of
      these higher upper reference limits to samples from supine patients with
      pheochromocytoma decreased the diagnostic sensitivity from 99% to 96%. In
      patients without pheochromocytoma, adjusting the plasma concentration for the
      effects of sitting while preserving the 99% sensitivity by use of the supine
      upper reference limits increased the number of false-positive test results from
      9% to 25%. CONCLUSIONS: To preserve high diagnostic sensitivity we recommend the
      use of upper reference limits determined from blood samples collected in the
      supine position. Under these conditions, negative test results for blood samples
      obtained with patients sitting are as effective for ruling out pheochromocytoma
      as negative results from samples obtained after supine rest. Repeat testing with
      samples obtained in the supine position offers a cost-effective approach for
      dealing with the increased numbers of false-positive results expected after
      initial sampling in the sitting position.

PMID- 17200133
TI  - Biomarkers of folate and vitamin B12 are related in blood and cerebrospinal
      fluid.
AB  - BACKGROUND: B-vitamins (folate, B(12)) are important micronutrients for brain
      function and essential cofactors for homocysteine (HCY) metabolism. Increased HCY
      has been related to neurological and psychiatric disorders. We studied the role
      of the B-vitamins in HCY metabolism in the brain. METHODS: We studied blood and
      cerebrospinal fluid (CSF) samples from 72 patients who underwent lumbar puncture.
      We measured HCY, methylmalonic acid (MMA), and cystathionine by gas
      chromatography-mass spectrometry; S-adenosylmethionine (SAM) and S
      adenosylhomocysteine (SAH) by liquid chromatography-tandem mass spectrometry; and
      the B-vitamins by HPLC or immunoassays. RESULTS: Concentrations were lower in CSF
      than serum or plasma for HCY (0.09 vs 9.4 micromol/L), SAH (13.2 vs 16.8 nmol/L),
      cystathionine (54 vs 329 nmol/L), and holotranscobalamin (16 vs 63 pmol/L),
      whereas concentrations in CSF were higher for MMA (359 vs 186 nmol/L) and SAM
      (270 vs 113 nmol/L; all P <0.05). CSF concentrations of HCY correlated
      significantly with CSF folate (r = -0.46), CSF SAH (r = 0.48), CSF-albumin (r =
      0.31), and age (r = 0.32). Aging was also associated with lower concentrations of
      CSF-folate and higher CSF-SAH. The relationship between serum and CSF folate
      depended on serum folate: the correlation (r) of serum and CSF-folate was 0.69 at
      serum folate <15.7 nmol/L. CSF concentrations of MMA and holotranscobalamin were
      not significantly correlated. CONCLUSIONS: CSF and serum/plasma concentrations of
      vitamin biomarkers are significantly correlated. Older age is associated with
      higher CSF-HCY and CSF-SAH and lower CSF-folate. These metabolic alterations may
      be important indicators of low folate status, hyperhomocysteinemia, and
      neurodegenerative diseases.

PMID- 17200134
TI  - Isoprostane measurement in plasma and urine by liquid chromatography-mass
      spectrometry with one-step sample preparation.
AB  - BACKGROUND: Isoprostane F(2alpha) (iPF(2alpha)-III) concentration in plasma and
      urine is widely accepted as a measure of oxidative stress. Gas chromatography
      mass spectrometry (GC/MS) methods for measuring iPF(2alpha)-III involve several
      steps of sample preparation and are labor-intensive, and ELISA methods, although
      easier to use, are less reliable. Therefore we developed a simple and sensitive
      method involving 1-step sample cleanup and HPLC/MS quantification. METHODS:
      Samples of plasma or urine were enriched with a deuterated (iPF(2alpha)-III-D4)
      standard, treated with KOH to liberate the bound isoprostanes, then loaded onto
      an immunoaffinity column, and the bound isoprostane was eluted with 95% ethanol.
      The concentrated sample was injected onto a C-18 HPLC column, and the isoprostane
      was eluted with a gradient of acetonitrile in water and analyzed by electrospray
      negative ionization, selectively monitoring the ions 353.2 (iPF(2alpha)-III) and
      357.2 (iPF(2alpha)-III-D4). The amount of isoprostane in the sample was
      calculated from the ratio of the intensities of the 2 ions. RESULTS: The
      described method has a detection limit of 0.5 ng/L, with a linear dynamic range
      of 1-5000 ng/L. The intra- and interassay imprecisions were 4.68% and 3.88%,
      respectively. The values obtained correlated strongly with the GC/MS procedure (r
      = 0.80), but the absolute values were approximately 4- to 5-fold lower, because
      the present method measures specifically 1 isomer of isoprostane, whereas the
      GC/MS method measures 4 isomers together. CONCLUSIONS: Because of its simplicity
      and lower limit of quantification, the present method provides a useful
      noninvasive tool for determining oxidative stress in patients.

PMID- 17200135
TI  - ProteinChip array profiling for identification of disease- and chemotherapy
      associated biomarkers of nasopharyngeal carcinoma.
AB  - BACKGROUND: We previously used ProteinChip array profiling analysis to discover a
      serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we
      used the same method to examine other biomarkers associated with NPC and response
      to chemotherapy (CT) in NPC patients. METHODS: We performed ProteinChip array
      analysis in 209 serum samples from 66 relapsed patients before and after salvage
      CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11
      patients in remission, and 35 healthy individuals. Intensities of the biomarker
      peaks were correlated with CT response of the patients and other clinical
      parameters. RESULTS: We discovered 13 candidate biomarkers associated with
      different clinical parameters. Two biomarkers (2803 and 3953 Da) were
      significantly increased in patients compared with controls at all stages of
      disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers
      correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were
      significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were
      significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers
      from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14
      855 Da) being significantly decreased and 1 (6701 Da) significantly increased in
      patients who did not respond to CT. Tandem mass spectrometric sequencing and/or
      immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of
      interalpha-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor
      4. CONCLUSIONS: Treatment-associated serum biomarkers found might serve to triage
      NPC patients for appropriate CT treatment.

PMID- 17200137
TI  - Abeta1-42 stimulates actin polymerization in hippocampal neurons through Rac1 and
      Cdc42 Rho GTPases.
AB  - A number of psychiatric and neurodegenerative disorders, such as Alzheimer's
      disease, are characterized by abnormalities in the neuronal cytoskeleton. Here,
      we find that the enhancement in actin polymerization induced by fibrillar amyloid
      beta peptide (Abeta) is associated with increased activity of Rac1/Cdc42 Rho
      GTPases. Rac1 upregulation involves the participation of Tiam1, a Rac guanine
      nucleotide exchange factor, where Abeta exposure leads to Tiam1 activation by a
      Ca(2+)-dependent mechanism. These results point to Rho GTPases as one of the
      targets in Abeta-induced neurodegeneration in Alzheimer's disease pathology, with
      a role in mediating changes in the actin cytoskeletal dynamics.

PMID- 17200136
TI  - Role for WNT16B in human epidermal keratinocyte proliferation and
      differentiation.
AB  - WNT signalling regulates a variety of cell functions including cell fate,
      polarity, and differentiation via the canonical or beta-catenin stabilisation
      pathway and/or the planar cell polarity or non-canonical pathway. We have
      previously demonstrated that two isoforms (A and B) from the WNT16 locus have
      differential expression in various adult human tissues. In this study we show
      that WNT16B but not WNT16A isoform was upregulated in basal cell carcinomas
      compared with normal skin. We further investigated the cellular and molecular
      functions of WNT16B in primary human epidermal keratinocytes and a keratinocyte
      cell line. Cellular expression of WNT16B neither stabilised beta-catenin nor
      activated the lymphoid enhancer factor or T-cell factor transcriptional reporter
      in primary keratinocytes. WNT16B activated the Jun-N-terminal kinase cascade
      suggesting the activation of a non-canonical WNT signalling pathway. Constitutive
      expression of WNT16B significantly enhanced the rate of cell proliferation and
      prolonged clonogenicity in primary keratinocytes. Silencing WNT16B by RNA
      interference reduced keratinocyte proliferation. Furthermore, overexpression of
      WNT16B induced a hyperproliferation phenotype in an organotypical culture system.
      This work presents the first evidence that WNT16B activates human keratinocyte
      proliferation possibly via a beta-catenin-independent non-canonical WNT
      transduction pathway.

PMID- 17200138
TI  - Cdc2-mediated Schwann cell migration during peripheral nerve regeneration.
AB  - Schwann cell migration facilitates peripheral nerve regeneration after injury. We
      have recently found increased activation of Cdc2 kinase in regenerating sciatic
      nerves. Here we show that Cdc2 phosphorylation of caldesmon regulates Schwann
      cell migration and nerve regeneration. A robust but transient increase in Cdc2
      expression was found in cultured Schwann cells prepared from the sciatic nerve in
      rats that had undergone crush injury for 7 days. These ;injury-preconditioned'
      Schwann cells exhibited enhanced migration compared with non-preconditioned
      control cells and treatment with the cdk inhibitor roscovitine prevented cell
      migration. After transduction with recombinant Cdc2 DNA adenoviral vectors,
      Schwann cells were implanted into sciatic nerves; those expressing wild-type Cdc2
      migrated further in the distal direction than those expressing dominant-negative
      Cdc2. We identified caldesmon as a downstream substrate of Cdc2 in Schwann cells
      and its phosphorylation by Cdc2 changed its subcellular localization.
      Overexpression of dominant-negative caldesmon significantly counteracted the
      migration effect caused by Cdc2. Finally, neurite outgrowth of cultured DRG
      sensory neurons, facilitated by co-culture with injury-preconditioned Schwann
      cells, was suppressed by roscovitine treatment. The results indicate that
      activation of the Cdc2-caldesmon pathway is necessary for Schwann cell migration
      and suggest a role for this pathway in peripheral axonal growth.

PMID- 17200139
TI  - Regulation of the arsenic-responsive transcription factor Yap8p involves the
      ubiquitin-proteasome pathway.
AB  - Toxic metals are ubiquitous in the environment and all organisms possess systems
      to evade toxicity and acquire tolerance. The Saccharomyces cerevisiae AP-1-like
      protein Yap8p (systematic name YPR199c; also known as Acr1p and Arr1p) confers
      arsenic tolerance by stimulating enhanced transcription of the arsenic-specific
      detoxification genes ACR2 and ACR3. Here, we report that Yap8p is regulated at
      the level of degradation. We show that Yap8p is stabilized in arsenite-exposed
      cells in a time- and dose-dependent manner. Yap8p degradation proceeds through
      the ubiquitin-proteasome pathway and is dependent on the ubiquitin-conjugating
      enzyme Ubc4p. Further, we show that mutants that are defective in the ubiquitin
      proteasome pathway display increased Yap8p levels and elevated expression of the
      Yap8p gene-target ACR3. Yap8p forms homodimers in vivo but dimerization is not
      regulated by arsenite. Instead, arsenite-stimulated Yap8p stabilization and
      transcriptional activation of ACR3 requires critical cysteine residues within
      Yap8p. Collectively, our data is consistent with a model where Yap8p is degraded
      by the ubiquitin-proteasome pathway in untreated cells, whereas arsenite-exposure
      results in Yap8p stabilization and gene activation. In this way, regulated
      degradation contributes to Yap8p control.

PMID- 17200140
TI  - Alternative RNA splicing complexes containing the scaffold attachment factor
      SAFB2.
AB  - The scaffold attachment factor SAFB1 and its recently discovered homologue SAFB2
      might provide an important link between pre-mRNA splicing, intracellular
      signalling and transcription. Using novel mono-specific antisera, we found
      endogenous SAFB2 protein has a different spatial distribution from SAFB1 within
      the nucleus where it is found in much larger nuclear complexes (up to 670 kDa in
      size), and a distinct pattern of expression in adult human testis. By contrast,
      SAFB1 protein predominantly exists either as smaller complexes or as a monomeric
      protein. Our results suggest stable core complexes containing components
      comprised of SAFB1, SAFB2 and the RNA binding proteins Sam68 and hnRNPG exist in
      parallel with free SAFB1 protein. We found that SAFB2 protein, like SAFB1, acts
      as a negative regulator of a tra2beta variable exon. Despite showing an
      involvement in splicing, we detected no stable interaction between SAFB proteins
      and SR or SR-related splicing regulators, although these were also found in
      stable higher molecular mass complexes. Each of the detected alternative splicing
      regulator complexes exists independently of intact nucleic acids, suggesting they
      might be pre-assembled and recruited to nascent transcripts as modules to
      facilitate alternative splicing, and/or they represent nuclear storage
      compartments from which active proteins are recruited.

PMID- 17200142
TI  - Cdc42 and ARP2/3-independent regulation of filopodia by an integral membrane
      lipid-phosphatase-related protein.
AB  - Filopodia are dynamic cell surface protrusions that are required for proper
      cellular development and function. We report that the integral membrane protein
      lipid-phosphatase-related protein 1 (LPR1) localizes to and promotes the
      formation of actin-rich, dynamic filopodia, both along the cell periphery and the
      dorsal cell surface. Regulation of filopodia by LPR1 was not mediated by cdc42 or
      Rif, and is independent of the Arp2/3 complex. We found that LPR1 can induce
      filopodia formation in the absence of the Ena/Vasp family of proteins, suggesting
      that these molecules are not essential for the development of the protrusions.
      Mutagenesis experiments identified residues and regions of LPR1 that are
      important for the induction of filopodia. RNA interference experiments in an
      ovarian epithelial cancer cell line demonstrated a role for LPR1 in the
      maintenance of filopodia-like membrane protrusions. These observations, and our
      finding that LPR1 is a not an active lipid phosphatase, suggest that LPR1 may be
      a novel integral membrane protein link between the actin core and the surrounding
      lipid layer of a nascent filopodium.

PMID- 17200143
TI  - The Shwartzman reaction repealed: an interview with Dr. Guido Sireci by Helene F.
      Rosenberg.

PMID- 17200144
TI  - IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells.
AB  - IL-4 has distinct effects on the differentiation and functional properties of
      CD8+ T cells. In vivo studies have shown that it is critical for the development
      of protective memory responses against tumors and infections by Leishmania and
      Plasmodium parasites. The intracellular signaling events mediated by IL-4/IL-4
      receptor (IL-4R) interactions on CD4+ T cells have been studied extensively;
      however, the nature of IL-4-induced signaling on CD8+ T cells has not been
      characterized. Using naive, activated, as well as differentiated CD8+ T cells, we
      show that IL-4 has a strong in vivo and in vitro antiapoptotic effect on
      activated and resting CD8+ T cells. We demonstrate that IL-4 induces the
      phosphorylation of the IL-4R, which is followed by the activation of at least two
      distinct intracellular signaling cascades: the Jak1/STAT6 and the insulin
      receptor substrate/PI-3K/protein kinase B pathways. We also found that IL-4
      induces the Jak3-mediated phosphorylation and nuclear migration of STAT1, STAT3,
      and STAT5 in naive, activated, as well as differentiated, IFN-gamma-producing
      CD8+ T cells. The induction of this broad signaling activity in CD8+ T cells
      coincides with a transcriptional activity of suppressors of cytokine signaling
      genes, which are decreased significantly in comparison with CD4+ T cells. To our
      knowledge, this report constitutes the first comprehensive analysis of the
      signaling events that shape CD8+ T cell responses to IL-4.

PMID- 17200141
TI  - Connexin43 increases the sensitivity of prostate cancer cells to TNFalpha-induced
      apoptosis.
AB  - To examine the effects of increased expression of connexin43 (Cx43) upon cell
      viability and response to cytotoxic agents, we expressed Cx43 in LNCaP and PC3
      prostate cancer cells by infection with a recombinant adenovirus (Ad-Cx43).
      Infection with Ad-Cx43 led to the formation of Cx43-containing gap junction
      plaques at appositional membranes and increased Lucifer Yellow transfer in LNCaP
      cells, but not in PC3 cells. The increased intercellular communication was
      blocked by co-infection with an adenovirus containing a dominant-negative Cx43
      (Ad-Cx43DN). Infection of LNCaP (but not PC3) cells with Ad-Cx43 greatly
      increased their sensitivity to killing by tumor necrosis factor alpha (TNFalpha),
      anti-Fas antibodies, and TRAIL as quantified using an MTS assay. The TNFalpha
      induced cell death was dependent on cell density, and it was associated with
      increased annexin V staining, an increased proportion of sub-G1 cells, and
      activation of caspase 8. The TNFalpha-induced effects on Ad-Cx43-infected LNCaP
      cells were blocked by co-infection with Ad-Cx43DN or by pre-incubation with
      neutralizing antibodies directed against TNFalpha receptor 1. These results
      demonstrate that TNFalpha induces apoptosis in LNCaP cells by signaling through
      TNFalpha receptor 1 and that expression of functional Cx43 gap junction channels
      increases their sensitivity to TNFalpha.

PMID- 17200145
TI  - Attenuated induction of epithelial and leukocyte serine antiproteases elafin and
      secretory leukocyte protease inhibitor in Crohn's disease.
AB  - Elafin (or skin-derived antileukoprotease) and secretory leukocyte protease
      inhibitor (SLPI) are serine antiproteases antagonizing human neutrophil elastase
      (HNE), thereby preventing tissue injury from excessive release of proteolytic
      enzymes by inflammatory cells. Furthermore, elafin and SLPI are "defensin-like"
      molecules with broad antimicrobial activity. The balance between proteases and
      antagonists may critically determine inflammatory processes in Crohn's disease
      (CD) and ulcerative colitis (UC). Real-time PCR was performed to quantitate
      colonic, proinflammatory cytokine IL-8, protease (HNE), and antiprotease mRNA
      (elafin and SLPI) in a total of 340 biopsies from 117 patients (47 CD, 45 UC, 25
      controls). Histological inflammation was scored, and HNE, elafin, and SLPI were
      localized and semiquantified by immunostaining in 51 colonic paraffin sections
      (23 CD, 11 UC, 17 controls). Proinflammatory IL-8, degree of histological
      inflammation, and granulocyte content were similar in UC and CD. Elafin stained
      predominantly in the epithelium and SLPI in mucosal inflammatory cells. HNE mRNA
      levels and immunostaining were increased equally in both forms of inflammatory
      bowel disease. Levels of mRNA and immunostaining of the antiproteases elafin and
      SLPI were enhanced strongly in inflamed versus noninflamed UC. It is surprising
      that comparing inflamed versus noninflamed CD, this increase was significantly
      less pronounced for elafin and even lacking for SLPI. Despite comparable degrees
      of inflammation and protease levels, the induction of both antiproteases was
      attenuated in CD. This could contribute to the transmural depth of tissue
      destruction in CD. Elafin and SLPI may be added to the list of defensin-like
      peptides with diminished induction in CD versus UC.

PMID- 17200146
TI  - Expression and function of cystine/glutamate transporter in neutrophils.
AB  - Reactive oxygen species (ROS) produced by neutrophils are essential in the host
      defense against infections but may be harmful to neutrophils themselves.
      Glutathione (GSH) plays a pivotal role in protecting cells against ROS-mediated
      oxidant injury. Cystine/glutamate transporter, designated as system xc- and
      consisting of two proteins, xCT and 4F2hc, is important to maintain GSH levels in
      mammalian-cultured cells. In the present paper, we have investigated system xc-
      in neutrophils. In human peripheral blood neutrophils, neither the activity of
      system xc- nor xCT mRNA was detected. The activity was induced, and xCT mRNA was
      expressed when they were cultured in vitro. The mRNA expression was much enhanced
      in the presence of opsonized zymosan or PMA. In contrast, mouse peritoneal
      exudate neutrophils, immediately after preparation, exhibited system xc- activity
      and expressed xCT mRNA. The activity and the expression were heightened further
      when they were cultured. Peritoneal exudate cells (mostly neutrophils) from xCT
      deficient (xCT-/-) mice had lower cysteine content than those from the wild-type
      mice. GSH levels in the xCT-/-cells decreased rapidly when they were cultured,
      whereas those in the wild-type cells were maintained during the culture.
      Apoptosis induced in culture was enhanced in the xCT-/-cells compared with the
      wild-type cells. These results suggest that system xc- plays an important role in
      neutrophils when they are activated, and their GSH consumption is accelerated.

PMID- 17200147
TI  - Protective role of IFN-gamma in collagen-induced arthritis conferred by
      inhibition of mycobacteria-induced granulocyte chemotactic protein-2 production.
AB  - Mice with a disrupted IFN-gamma system are remarkably susceptible to experimental
      autoimmune diseases, such as collagen-induced arthritis (CIA), which rely on the
      use of CFA. The inflammatory lesions of these IFN-gamma knockout (KO) mice are
      characterized by an excessive proportion of neutrophils. Here, we show that the
      increased severity of CIA in IFN-gammaR KO as compared with wild-type mice is
      accompanied by increased levels of the CXC chemokine granulocyte chemotactic
      protein-2 (GCP-2), a major neutrophil-attracting chemokine in mice. We
      demonstrated that the heat-killed mycobacteria present in CFA elicited production
      of GCP-2 in mouse embryo fibroblast cultures and that this production was
      inhibited by IFN-gamma. Inhibition of GCP-2 production by IFN-gamma was STAT-1
      dependent. IFN-gamma receptor KO mice treated with neutralizing anti-GCP-2
      antibodies were protected from CIA, indicating the in vivo importance of GCP-2 in
      the pathogenesis of CIA. Our data support the notion that one of the mechanisms
      whereby endogenous IFN-gamma mitigates the manifestations of CIA consists of
      inhibiting production of GCP-2, thereby limiting mobilization and infiltration of
      neutrophils, which are important actors in joint inflammation. These results may
      also be applicable to other experimental models of autoimmunity that rely on the
      use of CFA.

PMID- 17200148
TI  - Five years of letrozole compared with tamoxifen as initial adjuvant therapy for
      postmenopausal women with endocrine-responsive early breast cancer: update of
      study BIG 1-98.
AB  - PURPOSE: Previous analyses of the Breast International Group (BIG) 1-98 four-arm
      study compared initial therapy with letrozole or tamoxifen including patients
      randomly assigned to sequential treatment whose information was censored at the
      time of therapy change. Because this presentation may unduly reflect early
      events, the present analysis is limited to patients randomly assigned to the
      continuous therapy arms and includes protocol-defined updated results. PATIENTS
      AND METHODS: Four thousand nine hundred twenty-two of the 8,028 postmenopausal
      women with receptor-positive early breast cancer randomly assigned (double-blind)
      to the BIG 1-98 trial were assigned to 5 years of continuous adjuvant therapy
      with either letrozole or tamoxifen; the remainder of women were assigned to
      receive the agents in sequence. Disease-free survival (DFS) was the primary end
      point. RESULTS: At a median follow-up time of 51 months, we observed 352 DFS
      events among 2,463 women receiving letrozole and 418 events among 2,459 women
      receiving tamoxifen. This reflected an 18% reduction in the risk of an event
      (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .007). No predefined subsets
      showed differential benefit. Adverse events were similar to previous reports.
      Patients on tamoxifen experienced more thromboembolic events, endometrial
      pathology, hot flashes, night sweats, and vaginal bleeding. Patients on letrozole
      experienced more bone fractures, arthralgia, low-grade hypercholesterolemia, and
      cardiovascular events other than ischemia and cardiac failure. CONCLUSION: The
      present updated analysis, which was limited to patients on monotherapy arms in
      BIG 1-98, yields results similar to those from the previous primary analysis but
      more directly comparable with results from other trials of continuous therapy
      using a single endocrine agent.

PMID- 17200149
TI  - Gene-expression and immunohistochemical study of specific T-cell subsets and
      accessory cell types in the transformation and prognosis of follicular lymphoma.
AB  - PURPOSE: Despite the generally favorable clinical course in follicular lymphoma
      (FL), a minority of patients have a poor prognosis-with death within 3 years of
      diagnosis-most often due to transformation to aggressive disease. PATIENTS AND
      METHODS: In this study, we analyzed the potential of predicting early
      transformation on the basis of gene expression and immunologic parameters in FL
      biopsy samples taken at diagnosis. RESULTS: At the gene-expression level, FL is a
      highly uniform disease at the time of diagnosis, precluding the detection of
      sufficiently validated prognostic gene-expression profiles suitable for a
      clinical setting. Combinations of differentially expressed genes indicate that
      immunologic mechanisms play a differential role in the risk of early
      transformation. Using immunohistochemistry for specific cell populations, the
      spatial distribution to neoplastic follicles and the activation of CD4-positive T
      helper cells (P = .002) and specifically T-helper 1 (P = .004) were shown to be
      highly discriminatory to predict early transformation. A role for functional
      modulation of follicular dendritic cells could also be supported (P = .04). Other
      cell populations, including CD68-positive macrophages and regulatory T cells,
      were not differentially present. CONCLUSION: These results support the
      identification of FL as an immunologically functional disease in which an
      interaction of the tumor cells and the functional composition of the
      microenvironment determines the clinical behavior.

PMID- 17200150
TI  - Plasma phytoestrogens and subsequent breast cancer risk.
AB  - PURPOSE: Phytoestrogens are plant compounds that are structurally and
      functionally similar to mammalian estrogens. By competing for estrogen receptors,
      phytoestrogens possibly inhibit binding of the more potent endogenous estrogens
      and decrease their potential effects on breast cancer risk. We investigated the
      association between plasma phytoestrogen levels and breast cancer risk in a
      prospective manner. PATIENTS AND METHODS: We performed a nested case-control
      study within the Prospect cohort, one of the two Dutch cohorts participating in
      the European Prospective Investigation into Cancer and Nutrition. A total of 383
      women (87 pre- or perimenopausal women [mean age, 52 years] and 296
      postmenopausal women [mean age, 59 years]) who developed breast cancer were
      selected as case subjects and were matched to 383 controls, on date of blood
      sampling. Plasma levels of isoflavones (daidzein, genistein, glycitein, O
      desmethylangolensin, and equol) and lignans (enterodiol and enterolactone) were
      measured. The isotope dilution liquid chromatography/tandem mass-spectrometry
      method incorporating triply 13C-labeled standards was used for all analyses.
      Breast cancer odds ratios were calculated for tertiles of phytoestrogen plasma
      levels using conditional logistic regression analysis. RESULTS: For genistein,
      the risk estimate for the highest versus the lowest tertile was 0.68 (95% CI,
      0.47 to 0.98). Similar protective effects, although not statistically
      significant, were seen for the other isoflavones. Lignan levels did not appear to
      be related to breast cancer risk. Results were the same in pre- or perimenopausal
      women, and in postmenopausal women. CONCLUSION: High genistein circulation levels
      are associated with reduced breast cancer risk in the Dutch population. No
      effects of lignans on breast cancer risk were observed.

PMID- 17200151
TI  - SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon
      sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and
      torsinA.
AB  - Myoclonus-dystonia syndrome (MDS) is a genetically heterogeneous disorder
      characterized by myoclonic jerks often seen in combination with dystonia and
      psychiatric co-morbidities and epilepsy. Mutations in the gene encoding epsilon
      sarcoglycan (SGCE) have been found in some patients with MDS. SGCE is a
      maternally imprinted gene with the disease being inherited in an autosomal
      dominant pattern with reduced penetrance upon maternal transmission. In the
      central nervous system, epsilon-sarcoglycan is widely expressed in neurons of the
      cerebral cortex, basal ganglia, hippocampus, cerebellum and the olfactory bulb.
      epsilon-Sarcoglycan is located at the plasma membrane in neurons, muscle and
      transfected cells. To determine the effect of MDS-associated mutations on the
      function of epsilon-sarcoglycan we examined the biosynthesis and trafficking of
      wild-type and mutant proteins in cultured cells. In contrast to the wild-type
      protein, disease-associated epsilon-sarcoglycan missense mutations (H36P, H36R
      and L172R) produce proteins that are undetectable at the cell surface and are
      retained intracellularly. These mutant proteins become polyubiquitinated and are
      rapidly degraded by the proteasome. Furthermore, torsinA, that is mutated in DYT1
      dystonia, a rare type of primary dystonia, binds to and promotes the degradation
      of epsilon-sarcoglycan mutants when both proteins are co-expressed. These data
      demonstrate that some MDS-associated mutations in SGCE impair trafficking of the
      mutant protein to the plasma membrane and suggest a role for torsinA and the
      ubiquitin proteasome system in the recognition and processing of misfolded
      epsilon-sarcoglycan.

PMID- 17200152
TI  - Parkinson's disease-associated mutations in LRRK2 link enhanced GTP-binding and
      kinase activities to neuronal toxicity.
AB  - Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) cause late-onset
      Parkinson's disease indistinguishable from idiopathic disease. The mechanisms
      whereby missense alterations in the LRRK2 gene initiate neurodegeneration remain
      unknown. Here, we demonstrate that seven of 10 suspected familial-linked
      mutations result in increased kinase activity. Functional and disease-associated
      mutations in conserved residues reveal the critical link between intrinsic
      guanosine triphosphatase (GTPase) activity and downstream kinase activity. LRRK2
      kinase activity requires GTPase activity, whereas GTPase activity functions
      independently of kinase activity. Both LRRK2 kinase and GTPase activity are
      required for neurotoxicity and potentiate peroxide-induced cell death, although
      LRRK2 does not function as a canonical MAP-kinase-kinase-kinase. These results
      suggest a link between LRRK2 kinase activity and pathogenic mechanisms relating
      to neurodegeneration, further supporting a gain-of-function role for LRRK2
      mutations.

PMID- 17200153
TI  - Long-range conserved non-coding SHOX sequences regulate expression in developing
      chicken limb and are associated with short stature phenotypes in human patients.
AB  - Defects in long-range regulatory elements have recently emerged as previously
      underestimated factors in the genesis of human congenital disorders. Leri-Weill
      dyschondrosteosis is a dominant skeletal malformation syndrome caused by
      mutations in the short stature homeobox gene SHOX. We have analysed four families
      with Leri-Weill dyschondrosteosis with deletions in the pseudoautosomal region
      but still with an intact SHOX coding region. Using fluorescence in situ
      hybridization and single nucleotide polymorphism studies, we identified an
      interval of approximately 200 kb that was deleted in all tested affected family
      members but retained in the unaffected members and in 100 control individuals.
      Comparative genomic analysis of this interval revealed eight highly conserved non
      genic elements between 48 and 215 kb downstream of the SHOX gene. As mice do not
      have a Shox gene, we analysed the enhancer potential in chicken embryos using a
      green fluorescent protein reporter construct driven by the beta-globin promoter,
      by in ovo electroporation of the limb bud. We observed cis-regulatory activity in
      three of the eight non-genic elements in the developing limbs arguing for an
      extensive control region of this gene. These findings are consistent with the
      idea that the deleted region in the affected families contains several distinct
      elements that regulate Shox expression in the developing limb. Furthermore, the
      deletion of these elements in humans generates a phenotype apparently
      undistinguishable to those patients identified with mutations in the SHOX coding
      region and, for the first time, demonstrates the potential of an in vivo assay in
      chicken to monitor putative enhancer activity in relation to human disease.

PMID- 17200154
TI  - Physician-assisted suicide: Lord Joffe's Slippery Bill.

PMID- 17200155
TI  - My body, your body, our bodies.

PMID- 17200156
TI  - Vitamin E reduces glomerulosclerosis, restores renal neuronal NOS, and suppresses
      oxidative stress in the 5/6 nephrectomized rat.
AB  - Chronic kidney disease is accompanied by nitric oxide (NO) deficiency and
      oxidative stress, which contribute to progression. We investigated whether the
      antioxidant vitamin E could preserve renal function and NO bioavailability and
      reduce oxidative stress in the 5/6th nephrectomy (NX) rat model. We studied the
      following three groups of male Sprague-Dawley rats: sham (n = 6), 5/6 NX control
      (n = 6), and 5/6 NX treated with vitamin E (5,000 IU/kg chow; n = 5). The 5/6 NX
      group showed increased severity of glomerulosclerosis vs. sham, and this was
      ameliorated by vitamin E therapy. Both 5/6 NX groups showed similar elevations in
      plasma creatinine and proteinuria and decreased 24-h creatinine clearance
      compared with sham. There was increased NADPH-dependent superoxide production in
      5/6 NX rats vs. sham that was prevented by vitamin E. Total NO production was
      similarly reduced in both 5/6 NX groups. There was unchanged abundance of
      endothelial nitric oxide synthesis (NOS) in renal cortex and medulla and neuronal
      (n) NOS in medulla. However, in kidney cortex, 5/6 NX rats had lower nNOS
      abundance than sham, which was restored by vitamin E. An increased plasma
      asymmetric dimethylarginine occurred with 5/6 NX associated with decreased renal
      dimethylarginine dimethylaminohydrolase activity and increased type 1 protein
      arginine methyltransferase expression.

PMID- 17200158
TI  - Na channel expression and activity in the medullary collecting duct of rat
      kidney.
AB  - The expression and activity of epithelial Na(+) channels (ENaC) in the medullary
      collecting duct of the rat kidney were examined using a combination of whole cell
      patch-clamp measurements of amiloride-sensitive currents (I(Na)) in split-open
      tubules and Western blot analysis of alpha-, beta-, and gamma-ENaC proteins. In
      the outer medullary collecting duct, amiloride-sensitive currents were
      undetectable in principal cells from control animals but were robust when rats
      were treated with aldosterone (I(Na) = 960 +/- 160 pA/cell) or fed a low-Na diet
      (I(Na) = 440 +/- 120 pA/cell). In both cases, the currents were similar to those
      measured in principal cells of the cortical collecting duct from the same
      animals. In the inner medullary collecting duct, currents were much lower,
      averaging 120 +/- 20 pA/cell in aldosterone-treated rats. Immunoblots showed that
      all three ENaC subunits were expressed in the cortex, outer medulla, and inner
      medulla of the rat kidney. When rats were fed a low-Na diet for 1 wk, similar
      changes in alpha- and gamma-ENaC occurred in all three regions of the kidney; the
      amounts of full-length as well as putative cleaved alpha-ENaC protein increased,
      and the fraction of gamma-ENaC protein in the cleaved state increased at the
      expense of the full-length protein. The appearance of a presumably fully
      glycosylated form of beta-ENaC in Na-depleted animals was observed mainly in the
      outer and inner medulla. These findings suggest that the capability of hormone
      regulated, channel-mediated Na reabsorption by the nephron extends at least into
      the outer medullary collecting duct.

PMID- 17200159
TI  - Profiling of human mesangial cell subproteomes reveals a role for calmodulin in
      glucose uptake.
AB  - Proteomics combined with cell fractionation was used to identify proteins
      regulated by high glucose (HG) in human mesangial cells (HMC). Total membrane and
      cytosolic fraction proteins derived from HMC after 7 days of HG exposure were
      resolved by a two-dimensional gel electrophoresis approach. DeCyder software was
      used to analyze the HG-induced protein spot dysregulation. In the membrane
      subproteome, of the 92 spots that were matched across all gels, HG induced
      significant downregulation of only 4 protein spots. The dysregulated spots from
      the membrane subproteome included binding protein (BiP), calreticulin precursor
      protein, a 63-kDa transmembrane protein from a ER/Golgi intermediate, and beta
      subunit of collagen proline 4-hydroxylase. In the cytosolic subproteome, of the
      122 spots that were matched across all gels, HG induced downregulation of 3
      protein spots and upregulation of 2 protein spots significantly. Enolase 1,
      annexin VI, and gamma(2)-actin were decreased, whereas heat shock protein-70 kDa
      and calmodulin (CaM) were increased. Further confocal microscopy and Western
      immunoblotting of mesangial cells validated the increase in CaM. Immunoblotting
      of diabetic mouse and rat kidneys exhibited a marked increase in CaM at both
      early and late stages of diabetes, reflecting the potential physiological
      relevance of CaM upregulation. CaM-specific inhibitors blocked glucose transport
      stimulated by transforming growth factor-beta and insulin in mesangial cells. In
      conclusion, using a combination of cell fractionation and protein expression
      profiling, we identified a cohort of HG-dysregulated proteins in the HMC and
      identified a critical and as yet unrecognized role for CaM in glucose transport
      in mesangial cells.

PMID- 17200157
TI  - Lack of pendrin HCO3- transport elevates vestibular endolymphatic [Ca2+] by
      inhibition of acid-sensitive TRPV5 and TRPV6 channels.
AB  - The low Ca(2+) concentration ([Ca(2+)]) of mammalian endolymph in the inner ear
      is required for normal hearing and balance. We reported (Yamauchi et al., Biochem
      Biophys Res Commun 331: 1353-1357, 2005) that the epithelial Ca(2+) channels
      TRPV5 and TRPV6 (transient receptor potential types 5 and 6) are expressed in the
      vestibular system and that TRPV5 expression is stimulated by 1,25
      dihydroxyvitamin D(3), as also reported in kidney. TRPV5/6 channels are known to
      be inhibited by extracellular acidic pH. Endolymphatic pH, [Ca(2+)], and
      transepithelial potential of the utricle were measured in Cl(-)/HCO(3)(-)
      exchanger pendrin (SLC26A4) knockout mice in vivo. Slc26a4(-/-) mice exhibit
      reduced pH and utricular endolymphatic potential and increased [Ca(2+)].
      Monolayers of primary cultures of rat semicircular canal duct cells were grown on
      permeable supports, and cellular uptake of (45)Ca(2+) was measured individually
      from the apical and basolateral sides. Net uptake of (45)Ca(2+) was greater after
      incubation with 1,25-dihydroxyvitamin D(3). Net (45)Ca(2+) absorption was
      dramatically inhibited by low apical pH and was stimulated by apical alkaline pH.
      Gadolinium, lanthanum, and ruthenium red reduced apical uptake. These
      observations support the notion that one aspect of vestibular dysfunction in
      Pendred syndrome is a pathological elevation of endolymphatic [Ca(2+)] due to
      luminal acidification and consequent inhibition of TRPV5/6-mediated Ca(2+)
      absorption.

PMID- 17200160
TI  - The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid
      glands.
AB  - We previously demonstrated that extracellular calcium regulates vitamin D
      receptor (VDR) expression by parathyroid cells. Since the calcimimetic R-568
      potentiates the effects of calcium on the calcium-sensing receptor, it was
      hypothesized that administration of R-568 may result in increased VDR expression
      in parathyroid tissue. In vitro studies of the effect of R-568 on VDR mRNA and
      protein were conducted in cultures of whole rat parathyroid glands and human
      hyperplastic parathyroid glands. In vivo studies in Wistar rats examined the
      effect of R-568 and calcitriol alone and in combination. Incubation of rat
      parathyroid glands in vitro with R-568 (0.001-1 microM) resulted in a dose
      dependent decrease in parathyroid hormone (PTH) secretion and an increase in VDR
      expression (mean +/- SE). Incubation in 1 mM calcium + 0.001 microM R-568
      elicited an increase in VDR mRNA (306 +/- 46%) similar to the maximum increase
      detected with 1.5 mM calcium (330 +/- 42%). In vivo, VDR mRNA was increased after
      administration of R-568 (168 +/- 9%, P < 0.001 vs. control) or calcitriol (198 +/
      16%, P < 0.001 vs. control). Treatment with R-568 also increased VDR protein in
      normal rat parathyroid glands and in human parathyroid glands with diffuse, but
      not nodular, hyperplasia. In conclusion, the present study shows that the
      calcimimetic R-568 exerts a stimulatory effect on VDR expression in the
      parathyroid glands of study models and provides additional evidence for the use
      of calcimimetics in the treatment of secondary hyperparathyroidism.

PMID- 17200161
TI  - End-stage renal disease causes an imbalance between endothelial and smooth muscle
      progenitor cells.
AB  - Patients with end-stage renal disease (ESRD) on hemodialysis have an increased
      risk of cardiovascular disease (CVD). Circulating endothelial progenitor cells
      (EPC) contribute to vascular regeneration and repair, thereby protecting against
      CVD. However, circulating smooth muscle progenitor cells (SPC) may contribute to
      adverse vascular remodeling. We hypothesized that an imbalance occurs between EPC
      and SPC in ESRD patients and sampled progenitor cells from 45 ESRD patients
      receiving regular treatment. Our study is the first to show reduced numbers of
      CD34+KDR+ hematopoietic stem cell (HSC)-derived EPC (type I EPC). Furthermore,
      monocyte-derived EPC cultured from mononuclear cells (type II EPC) were reduced
      in number and had a reduced capacity to stimulate endothelial cell angiogenesis.
      In contrast, SPC outgrowth was unaffected. In vitro incubation with uremic serum
      impaired type II EPC outgrowth from healthy donor mononuclear cells and did not
      influence SPC outgrowth. The hemodialysis procedure itself induced HSC apoptosis
      and caused an acute depletion of circulating EPC. Taken together, the decreased
      number and impaired function of EPC are compatible with impaired endogenous
      vascular repair in hemodialysis patients, whereas the unaffected SPC numbers
      suggest that the potential of progenitor cells to contribute to adverse
      remodeling is retained. This EPC-SPC imbalance may contribute to the acceleration
      of CVD in ESRD patients and could offer novel therapeutic targets.

PMID- 17200162
TI  - Analysis of the Fc receptor-like-3 (FCRL3) locus in Caucasians with autoimmune
      disorders suggests a complex pattern of disease association.
AB  - CONTEXT: A four-marker haplotype in the 5' region of the Fc receptor-like 3 gene
      (markers FCRL3_3 to FCRL3_6) has been identified recently as contributing to
      rheumatoid arthritis (RA) susceptibility in the Japanese population. The promoter
      FCRL3_3*C allele also showed significant association with autoimmune thyroid
      disease and systemic lupus erythematosus. These findings raise the possibility
      that this locus may influence autoimmune disease susceptibility across many
      populations. PATIENTS AND DESIGN: We analyzed the same four 5' FCRL3 single
      nucleotide polymorphism markers, together with three additional exonic single
      nucleotide polymorphisms in the FCRL3 gene, in cohorts of white Caucasians with
      Graves' disease (n = 625), type 1 diabetes (n = 279), autoimmune Addison's
      disease (AAD; n = 200), and RA (n = 769). Healthy controls from the United
      Kingdom (n = 490) and New Zealand (n = 593) were used. RESULTS: Six of the seven
      FCRL3 markers showed association with AAD (P = 0.005-0.0001), with maximum
      evidence at the FCRL3_3*T allele [P([corrected]) = 0.0008; odds ratio (OR), 1.61;
      5-95% confidence intervals (CIs), 1.26-2.05]. The most common seven-marker FCRL3
      haplotype (TGGGAAA) was also found to be significantly associated with AAD
      (P([corrected]) = 1.1 x 10(-4); OR, 1.71; 5-95% CIs, 1.33-2.18). There was
      nominal evidence for allelic association at the marker FCRL3_8 in Graves' disease
      (OR, 1.50; 5-95% CIs, 1.06-2.13) and at FCRL3_9 with RA (OR, 1.25; 5-95% CIs,
      1.01-1.54). CONCLUSIONS: The FCRL3 haplotype that is associated with AAD in
      Caucasians appears to be protective for autoimmune diseases in the Japanese
      population, demonstrating that this haplotype is unlikely to contain a single
      primary etiological allele for autoimmunity. Our observations suggest that the
      susceptibility to autoimmunity at the FCRL3 locus is more complex than initially
      thought and may extend either side of the currently associated region to include
      the adjacent FCRL2 gene.

PMID- 17200163
TI  - Urine iodine measurements, creatinine adjustment, and thyroid deficiency in an
      adult United States population.
AB  - PURPOSE: The purpose of the study was to explore the relationships between urine
      iodine, creatinine, serum TSH, and total T(4) in a diverse population of U.S.
      adults with the aim of determining whether low urine iodine is associated with
      thyroid deficiency. METHODS: Using the Health and Nutrition Surveys III data set,
      we examined median TSH and total T(4) values according to deciles of urine iodine
      (with and without creatinine correction). Stepwise regression analysis was used
      to further explore these relationships in the context of possible confounding
      variables. Exclusion criteria included age less than 21 yr, pregnancy, and the
      presence of thyroid antibodies. RESULTS: Among the 5963 men and 5722 women,
      median urine iodine concentrations do not vary with increasing age, whereas
      median creatinine levels decrease (P < 0.001). Urine iodine and creatinine
      concentrations are lower among women (P < 0.001). TSH increases with age (P <
      0.001), whereas total T(4) decreases (P < 0.001). Neither TSH nor total T(4)
      median values are associated with urine iodine. If the urine iodine to creatinine
      ratio is used instead, an extensive redistribution of study subjects occurs that
      results in an apparent positive relationship between this ratio and TSH
      measurements. A multivariate regression analysis that accounts for age, body mass
      index, race, creatinine, iodine, estrogen use, smoking, and gender reveals only a
      weak association between levels of urine iodine and markers of thyroid function.
      CONCLUSIONS: Our analyses indicate that the U.S. nonpregnant adult population is
      iodine sufficient.

PMID- 17200164
TI  - Management of the child born small for gestational age through to adulthood: a
      consensus statement of the International Societies of Pediatric Endocrinology and
      the Growth Hormone Research Society.
AB  - OBJECTIVE: Low birth weight remains a major cause of morbidity and mortality in
      early infancy and childhood. It is associated with an increased risk of health
      problems later in life, particularly coronary heart disease and stroke. A meeting
      was convened to identify the key health issues facing a child born small for
      gestational age (SGA) and to propose management strategies. PARTICIPANTS: There
      were 42 participants chosen for their expertise in obstetrics, peri- and neonatal
      medicine, pediatrics, pediatric and adult endocrinology, epidemiology, and
      pharmacology. EVIDENCE: Written materials were exchanged, reviewed, revised, and
      then made available to all. This formed the basis for discussions at the meeting.
      Where published data were not available or adequate, discussion was based on
      expert clinical opinions. CONSENSUS PROCESS: Each set of questions was considered
      by all and then discussed in plenary sessions with consensus and unresolved
      issues identified. The consensus statement was prepared in plenary sessions and
      then edited by the group chairs and shared with all participants. CONCLUSIONS:
      The diagnosis of SGA should be based on accurate anthropometry at birth including
      weight, length, and head circumference. We recommend early surveillance in a
      growth clinic for those without catch-up. Early neurodevelopment evaluation and
      interventions are warranted in at-risk children. Endocrine and metabolic
      disturbances in the SGA child are recognized but infrequent. For the 10% who lack
      catch-up, GH treatment can increase linear growth. Early intervention with GH for
      those with severe growth retardation (height sd score, <-2.5; age, 2-4 yr) should
      be considered at a dose of 35-70 microg/kg x d. Long-term surveillance of treated
      patients is essential. The associations at a population level between low birth
      weight, including SGA, and coronary heart disease and stroke in later life are
      recognized, but there is inadequate evidence to recommend routine health
      surveillance of all adults born SGA outside of normal clinical practice.

PMID- 17200165
TI  - Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 activity in vivo limits
      glucocorticoid exposure to human adipose tissue and decreases lipolysis.
AB  - CONTEXT: The pathophysiological importance of glucocorticoids (GCs) is
      exemplified by patients with Cushing's syndrome who develop hypertension,
      obesity, and insulin resistance. At a cellular level, availability of GCs to the
      glucocorticoid and mineralocorticoid receptors is controlled by the isoforms of
      11beta-hydroxysteroid dehydrogenase (11beta-HSD). In liver and adipose tissue,
      11beta-HSD1 converts endogenous, inactive cortisone to active cortisol but also
      catalyzes the bioactivation of the synthetic prednisone to prednisolone.
      OBJECTIVE: The objective of the study was to compare markers of 11beta-HSD1
      activity and demonstrate that inhibition of 11beta-HSD1 activity limits
      glucocorticoid availability to adipose tissue. DESIGN AND SETTING: This was a
      clinical study. PATIENTS: Seven healthy male volunteers participated in the
      study. INTERVENTION: Intervention included carbenoxolone (CBX) single dose (100
      mg) and 72 hr of continuous treatment (300 mg/d). MAIN OUTCOME MEASURES:
      Inhibition of 11beta-HSD1 was monitored using five different mechanistic
      biomarkers (serum cortisol and prednisolone generation, urinary corticosteroid
      metabolite analysis by gas chromatography/mass spectrometry, and adipose tissue
      microdialysis examining cortisol generation and glucocorticoid-mediated glycerol
      release). RESULTS: Each biomarker demonstrated reduced 11beta-HSD1 activity after
      CBX administration. After both a single dose and 72 hr of treatment with CBX,
      cortisol and prednisolone generation decreased as did the urinary
      tetrahydrocortisol+5alpha-tetrahydrocortisol to tetrahydrocortisone ratio. Using
      adipose tissue microdialysis, we observed decreased interstitial fluid cortisol
      availability with CBX treatment. Furthermore, a functional consequence of 11beta
      HSD1 inhibition was observed, namely decreased prednisone-induced glycerol
      release into adipose tissue interstitial fluid indicative of inhibition of GC
      mediated lipolysis. CONCLUSION: CBX is able to inhibit rapidly the generation of
      active GC in human adipose tissue. Importantly, limiting GC availability in vivo
      has functional consequences including decreased glycerol release.

PMID- 17200166
TI  - Mapping of human autoantibody epitopes on aromatic L-amino acid decarboxylase.
AB  - CONTEXT: Aromatic l-amino acid decarboxylase (AADC) is target of autoantibodies
      in autoimmune polyendocrine syndrome I (APS I), especially in patients with
      autoimmune hepatitis. Little information is currently available on AADC
      autoantibody epitopes and on the interrelation between autoantibody-mediated
      inhibition of enzymatic activity and epitope specificity. DESIGN: We tested the
      immunoreactivity of full-length porcine AADC and of eight fragments of the enzyme
      with human serum from 18 patients with APS I, 199 with non-APS I autoimmune
      Addison's disease, 124 with type 1 diabetes mellitus, 36 with Graves' disease,
      and 141 healthy control subjects, and we evaluated the autoantibody-mediated
      enzymatic inhibition. RESULTS: AADC antibodies (Ab) were detected in 12 of 18
      (67%) APS I patients and in six of 199 (3%) autoimmune Addison's disease
      patients. Four patients with autoimmune hepatitis were all positive for AADCAb.
      None of the 141 healthy control subjects, 82 patients with nonautoimmune adrenal
      insufficiency, 124 with type 1 diabetes mellitus, and 36 with Graves' disease
      were found positive. Two epitope regions, corresponding to amino acids 274-299
      (E1) and 380-471 (E2) were identified. Localization of E1 was confirmed by
      displacement studies with synthetic peptides corresponding to peptides of porcine
      AADC. All 12 AADCAb-positive APS I sera reacted with E1, and seven of 12 (58%)
      reacted also with E2. E2-specific, but not E1-specific, autoantibodies were
      associated with a significant inhibition of in vitro AADC enzymatic activity.
      CONCLUSIONS: We mapped the human AADCAb epitopes to the middle and COOH-terminal
      regions of the enzyme. Autoantibodies to the COOH-terminal region induce a
      significant inhibition of enzymatic activity.

PMID- 17200167
TI  - Clinical presentations, biochemical phenotypes, and genotype-phenotype
      correlations in patients with succinate dehydrogenase subunit B-associated
      pheochromocytomas and paragangliomas.
AB  - CONTEXT: Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB)
      predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in
      apparently sporadic PGL directs appropriate treatment and family screening.
      OBJECTIVE: The objective of the study was to assess mutation-specific clinical
      and biochemical characteristics of SDHB-related PGL. DESIGN: The study design was
      retrospective descriptive. PATIENTS: PATIENTS included 29 patients (16 males)
      with SDHB-related abdominal or thoracic PGL. INTERVENTION: There was no
      intervention. MAIN OUTCOME MEASURES: Clinical presentations, plasma and urine
      concentrations of catecholamines and O-methylated metabolites, and genotype
      phenotype correlations were measured. RESULTS: Mean +/- sd age at diagnosis was
      33.7 +/- 15.7 yr. Tumor-related pain was among the presenting symptoms in 54% of
      patients and was the sole symptom in 14%. Seventy-six percent had hypertension,
      and 90% lacked a family history of PGL. All primary tumors but one originated
      from extraadrenal locations. Mean +/- sd tumor size was 7.8 +/- 3.7 cm. In this
      referral-based study, 28% presented with metastatic disease and all but one
      eventually developed metastases after 2.7 +/- 4.1 yr. Ten percent had additional
      head and neck PGLs. The biochemical phenotype was consistent with hypersecretion
      of both norepinephrine and dopamine in 46%, norepinephrine only in 41%, and
      dopamine only in 3%. Ten percent had normal catecholamine (metabolite) levels,
      consistent with biochemically silent PGL. No obvious genotype-phenotype
      correlations were identified. CONCLUSIONS: SDHB-related PGL often presents as
      apparently sporadic PGL with symptoms related to tumor mass effect rather than to
      catecholamine excess. The predominant biochemical phenotype consists of
      hypersecretion of norepinephrine and/or dopamine, whereas 10% of tumors are
      biochemically silent. The clinical expression of these tumors cannot be predicted
      by the genotype.

PMID- 17200168
TI  - Association between blood pressure and serum thyroid-stimulating hormone
      concentration within the reference range: a population-based study.
AB  - CONTEXT: The association between thyroid function and blood pressure is
      insufficiently studied. OBJECTIVE: The objective of the investigation was to
      study the association between TSH within the reference range and blood pressure.
      DESIGN AND SETTING: This was a cross-sectional, population-based study. SUBJECTS:
      A total of 30,728 individuals without previously known thyroid disease were
      studied. MAIN OUTCOME MEASURES: The main outcome measures were mean systolic and
      diastolic blood pressure and pulse pressure and odds ratio for hypertension
      (>140/90 mm Hg or current or previous use of antihypertensive medication),
      according to categories of TSH. RESULTS: Within the reference range of TSH (0.50
      3.5 mU/liter), there was a linear increase in blood pressure with increasing TSH.
      The average increase in systolic blood pressure was 2.0 mm Hg [95% confidence
      interval (CI) 1.4-2.6 mm Hg] per milliunit per liter increase in TSH among men,
      and 1.8 mm Hg (95% CI 1.4-2.3 mm Hg) in women. The corresponding increase in
      diastolic blood pressure was 1.6 mm Hg (95% CI 1.2-2.0 mm Hg) in men and 1.1 mm
      Hg (95% CI 0.8-1.3 mm Hg) in women. Comparing TSH of 3.0-3.5 mU/liter (upper part
      of the reference) with TSH of 0.50-0.99 mU/liter (lower part of the reference),
      the odds ratio for hypertension was 1.98 (95% CI 1.56-2.53) in men and 1.23 (95%
      CI 1.04-1.46) in women. CONCLUSION: Within the reference range of TSH, we found a
      linear positive association between TSH and systolic and diastolic blood pressure
      that may have long-term implications for cardiovascular health.

PMID- 17200169
TI  - Effect of calorie restriction with or without exercise on body composition and
      fat distribution.
AB  - CONTEXT: There is debate over the independent and combined effects of dieting and
      increased physical activity on improving metabolic risk factors (body composition
      and fat distribution). OBJECTIVE: The objective of the study was to conduct a
      randomized, controlled trial (CALERIE) to test the effect of a 25% energy deficit
      by diet alone or diet plus exercise for 6 months on body composition and fat
      distribution. DESIGN: This was a randomized, controlled trial. SETTING: The study
      was conducted at an institutional research center. PARTICIPANTS: Thirty-five of
      36 overweight but otherwise healthy participants (16 males, 19 females) completed
      the study. INTERVENTION: Participants were randomized to either control (healthy
      weight maintenance diet, n = 11), caloric restriction (CR; 25% reduction in
      energy intake, n = 12), or caloric restriction plus exercise (CR+EX; 12.5%
      reduction in energy intake + 12.5% increase in exercise energy expenditure, n =
      12) for 6 months. MAIN OUTCOME MEASURES: Changes in body composition by dual
      energy x-ray absorptiometry and changes in abdominal fat distribution by
      multislice computed tomography were measured. RESULTS: The calculated energy
      deficit across the intervention was not different between CR and CR+EX.
      Participants lost approximately 10% of body weight (CR: - 8.3 +/- 0.8, CR+EX: -
      8.1 +/- 0.8 kg, P = 1.00), approximately 24% of fat mass (CR: - 5.8 +/- 0.6,
      CR+EX: - 6.4 +/- 0.6 kg, P = 0.99), and 27% of abdominal visceral fat (CR: 0.9 +/
      0.2, CR+EX: 0.8 +/- 0.2 kg, P = 1.00). Both whole-body and abdominal fat
      distribution were not altered by the intervention. CONCLUSION: Exercise plays an
      equivalent role to CR in terms of energy balance; however, it can also improve
      aerobic fitness, which has other important cardiovascular and metabolic
      implications.

PMID- 17200171
TI  - Mortality in patients treated for Cushing's disease is increased, compared with
      patients treated for nonfunctioning pituitary macroadenoma.
AB  - CONTEXT: Increased mortality in patients with pituitary tumors after surgical
      treatment has been reported. However, it is unknown to what extent excess
      mortality is caused by pituitary tumors and their treatment in general and to
      what extent by previous exposure to hormonal overproduction. OBJECTIVE: The aim
      of the study was to compare mortality between patients treated for Cushing's
      disease and nonfunctioning pituitary macroadenomas (NFMAs). DESIGN: This was a
      follow-up study. PATIENTS: We included 248 consecutive patients with pituitary
      adenomas treated by transsphenoidal surgery in our hospital for NFMAs (n = 174)
      and ACTH-producing adenomas (n = 74). The mean duration of follow-up after
      surgery was 10.1 +/- 7.2 yr for the whole cohort. OUTCOME MEASURES: The
      standardized mortality ratio (SMR) was calculated for the whole cohort and also
      for the two diseases separately. Cox regression analysis was used to compare
      mortality in patients with Cushing's disease with NFMA patients. RESULTS:
      Patients with Cushing's disease (39.1 +/- 16.1 yr) were significantly younger at
      time of operation than NFMA patients (55.3 +/- 13.4 yr). The SMR for the whole
      cohort was 1.41 [95% confidence interval (CI), 1.05-1.86]. The SMR in NFMA
      patients was 1.24 (95% CI, 0.85-1.74) vs. 2.39 (95% CI, 1.22-3.9) in patients
      with Cushing's disease. In patients with Cushing's disease, compared with NFMAs,
      the age-adjusted mortality was significantly increased: hazard ratio 2.35 (95%
      CI, 1.13-4.09, P = 0.008). CONCLUSIONS: Mortality in patients previously treated
      for Cushing's disease is increased, compared with patients treated for NFMAs.
      This implies that previous, transient overexposure to cortisol is associated with
      increased mortality.

PMID- 17200170
TI  - Reduction in midthigh low-density muscle with aerobic exercise training and
      weight loss impacts glucose tolerance in older men.
AB  - CONTEXT: Intramuscular lipid content increases with aging and obesity and is
      directly related to impaired glucose tolerance and insulin resistance. OBJECTIVE:
      Our purpose was to determine the effects of aerobic exercise training (AEX) with
      and without weight loss (WL) on midthigh low-density muscle (LDM; a measure of im
      lipid) and whether changes in LDM impact glucose tolerance in sedentary older
      men. DESIGN: Forty-six men (60.4 +/- 1.1 yr) completed 6 months of AEX (n = 34)
      or AEX + WL (n = 12) and had oral glucose tolerance tests (OGTTs) and computed
      tomography measures of LDM and regional abdominal and thigh fat depot areas.
      RESULTS: At baseline, LDM area directly correlated with fasting plasma glucose
      (FPG), 120-min glucose (G(120)), and glucose area under the curve (G(AUC)) during
      an OGTT (r = 0.44, r = 0.51, and r = 0.54, respectively, P < 0.01). After the
      interventions, the AEX + WL group had greater decreases in LDM (-13.5 vs. +1.3%,
      respectively), FPG (-8.3 vs. +2.1%, respectively), G(120) (-22.5 vs. -3.6%,
      respectively), and G(AUC) (-17.3 vs. - 3.1%, respectively) than the AEX group. In
      the entire sample, the decreases in LDM correlated with reductions in FPG,
      G(120), and G(AUC) during an OGTT (r = 0.31, r = 0.34, and r = 0.41, P < 0.05).
      Changes in other regional fat depots did not independently correlate with glucose
      tolerance or insulin responses. CONCLUSION: AEX + WL is more efficacious than AEX
      for reducing LDM and glucose tolerance. The improvement in glucose tolerance may
      be partially mediated by decreases in LDM in older men.

PMID- 17200172
TI  - Discontinuation of antiresorptive therapies: a comparison between 1998-2001 and
      2002-2004 among osteoporotic women.
AB  - CONTEXT: Studies having reported high rates of discontinuation of antiresorptive
      therapies (ART) may not reflect their actual use. OBJECTIVES: We compared
      probability of discontinuation among women aged 70 yr or older with a diagnosis
      of osteoporosis or recent osteoporotic fracture having started ART (alendronate,
      risedronate, cyclical etidronate, raloxifene, nasal calcitonin) between 1998-2001
      or 2002-2004. PATIENTS AND METHODS: We constructed two cohorts of women using
      Regie de l'Assurance Maladie du Quebec databases. Discontinuation was defined as
      a lapse of 30 d or longer after completion of a refill. Switching from one ART to
      another was allowed. Probability of discontinuation was estimated using Kaplan
      Meier analysis. Multivariate Cox models were used to identify potential
      determinants of ART discontinuation over 1 yr. RESULTS: After 1 yr, probability
      of discontinuation was slightly lower in the 2002-2004 cohort than the 1998-2001
      cohort (52.2 vs. 57.5%; P < 0.001). This difference remained significant after
      adjusting for determinants [adjusted rate ratio (RR) 0.92, 95% confidence
      interval (CI) 0.87-0.98]. Significant determinants of ART discontinuation within
      1 yr included bone mineral density testing (RR 0.77; CI 0.73-0.82) performed
      within 2 yr prior to initiation of therapy and having consulted more than two
      pharmacies (RR 1.15; CI 1.06-1.25) in the year before starting therapy. In the
      2002-2004 cohort, when switching was allowed, women initiating a once-weekly
      regimen of alendronate or risedronate did not show a 1-yr risk of discontinuation
      different from women initiating daily regimens of the same drugs (RR 0.90; CI
      0.82-1.00). CONCLUSIONS: Even if new dosing regimens were introduced,
      discontinuation of ART among osteoporotic women remains high.

PMID- 17200173
TI  - Functional single-nucleotide polymorphisms in the secretogranin III (SCG3) gene
      that form secretory granules with appetite-related neuropeptides are associated
      with obesity.
AB  - CONTEXT: Genetic factors are important for the development of obesity. However,
      the genetic background of obesity still remains unclear. OBJECTIVE: Our objective
      was to search for obesity-related genes using a large number of gene-based single
      nucleotide polymorphisms (SNPs). DESIGN AND SETTING: We conducted case-control
      association analyses using 94 obese patients and 658 controls with 62,663 SNPs
      selected from the SNP database. SNPs that possessed P < or = 0.02 were further
      analyzed using 796 obese and 711 control subjects. One SNP (rs3764220) in the
      secretogranin III (SCG3) gene showed the lowest P value (P = 0.0000019). We
      sequenced an approximately 300-kb genomic region around rs3764220 and discovered
      SNPs for haplotype analyses. SCG3 was the only gene within a haplotype block that
      contained rs3764220. The functions of SCG3 were studied. PATIENTS: Obese subjects
      (body mass index > or = 30 kg/m(2), n = 890) and control subjects (general
      population; n = 658, body mass index < or = 25 kg/m(2); n = 711) were recruited
      for this study. RESULTS: Twelve SNPs in the SCG3 gene including rs3764220 were in
      almost complete linkage disequilibrium and significantly associated with an
      obesity phenotype. Two SNPs (rs16964465, rs16964476) affected the transcriptional
      activity of SCG3, and subjects with the minor allele seemed to be resistant to
      obesity (odds ratio, 9.23; 95% confidence interval, 2.77-30.80; chi(2) = 19.2; P
      = 0.0000067). SCG3 mRNA and immunoreactivity were detected in the paraventricular
      nucleus, lateral hypothalamic area, and arcuate nucleus, and the protein
      coexisted with orexin, melanin-concentrating hormone, neuropeptide Y, and
      proopiomelanocortin. SCG3 formed a granule-like structure together with these
      neuropeptides. CONCLUSIONS: Genetic variations in the SCG3 gene may influence the
      risk of obesity through possible regulation of hypothalamic neuropeptide
      secretion.

PMID- 17200174
TI  - Cardiovascular risk factors and ultrasound evaluation of intima-media thickness
      at common carotids, carotid bulbs, and femoral and abdominal aorta arteries in
      patients with classic congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency.
AB  - CONTEXT: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency, a tendency for obesity, high insulin, and high 24-h blood pressure
      levels has been reported in children and adolescents. Increased intima-media
      thickness (IMT) is considered a measure of subclinical atherosclerosis and a
      predictor of myocardial infarction and stroke. OBJECTIVE: The objective of the
      study was to evaluate glucose metabolism, lipid profile, IMT of the abdominal
      aorta, right and left common carotids, carotid bulbs, and common femoral arteries
      in adult CAH patients. SUBJECTS: Nineteen (10 females, nine males; 28 +/- 3.5 yr)
      patients (12 salt wasting and seven simple virilizing) and 19 (10 females, nine
      males) healthy subjects matched for anthropometric parameters (age, sex, body
      mass index, smoking habit, waist to hip ratio, and blood pressure). METHODS:
      Glucose metabolism was studied using the oral glucose tolerance test and the
      homeostasis model assessment-insulin resistance. The echo-Doppler was used for
      arterial ultrasound. 17-Hydroxyprogesterone, androstenedione, testosterone, ACTH,
      plasma renin activity, total and high-density lipoprotein cholesterol, and
      triglycerides were measured. RESULTS: CAH patients had significantly higher
      fasting plasma insulin (11.6 +/- 6.20 microU/ml vs 5.18 +/- 2.4 microU/ml; P <
      0.0001) and homeostasis model assessment-insulin resistance than controls (2.46
      +/- 1.92 vs 1.12 +/- 0.58; P = 0.0033). IMT of the studied arteries was higher in
      CAH patients than controls. There was no correlation between IMT and cumulative
      glucocorticoid doses and androgen levels. CONCLUSION: A reduced insulin
      sensitivity and increased IMT were demonstrated in adults with CAH, who
      consequently need a follow-up for cardiovascular risk.

PMID- 17200175
TI  - Heterozygous missense mutations in steroidogenic factor 1 (SF1/Ad4BP, NR5A1) are
      associated with 46,XY disorders of sex development with normal adrenal function.
AB  - CONTEXT: Steroidogenic factor 1 (SF1/AdBP4/FTZF1, NR5A1) is a nuclear receptor
      transcription factor that plays a key role in regulating adrenal and gonadal
      development, steroidogenesis, and reproduction. Targeted deletion of Nr5a1 (Sf1)
      in the mouse results in adrenal and gonadal agenesis, XY sex-reversal, and
      persistent Mullerian structures in males. Consistent with the murine phenotype,
      human mutations in SF1 were described initially in two 46,XY individuals with
      female external genitalia, Mullerian structures (uterus), and primary adrenal
      failure. OBJECTIVE: Given recent case reports of haploinsufficiency of SF1
      affecting testicular function in humans, we aimed to identify SF1 mutations in a
      cohort of individuals with a phenotypic spectrum of 46,XY gonadal
      dysgenesis/impaired androgenization (now termed 46,XY disorders of sex
      development) with normal adrenal function. METHODS AND PATIENTS: The study
      included mutational analysis of NR5A1 in 30 individuals with 46,XY disorders of
      sex development, followed by functional studies of SF1 activity. RESULTS:
      Heterozygous missense mutations in NR5A1 were found in four individuals (four of
      30, 13%) with this phenotype. These mutations (V15M, M78I, G91S, L437Q) were
      shown to impair transcriptional activation through abnormal DNA binding (V15M,
      M78I, G91S), altered subnuclear localization (V15M, M78I), or disruption of the
      putative ligand-binding pocket (L437Q). Two mutations appeared to be de novo or
      germline changes. The other two mutations appeared to be inherited in a sex
      limited dominant manner because the mother is heterozygous for the change.
      CONCLUSIONS: These studies demonstrate that SF1 mutations are more frequent than
      previously suspected causes of impaired fetal and postnatal testicular function
      in 46,XY individuals.

PMID- 17200176
TI  - A mutation in the fibroblast growth factor receptor 1 gene causes fully penetrant
      normosmic isolated hypogonadotropic hypogonadism.
AB  - CONTEXT: Kallmann syndrome (KS) consists of idiopathic hypogonadotropic
      hypogonadism (IHH) and anosmia/hyposmia. Currently, the fibroblast growth factor
      receptor 1 (FGFR1) gene is the only known autosomal dominant cause of KS, which
      is also associated with synkinesia, midfacial defects, and dental agenesis.
      OBJECTIVE: Mutations in FGFR1 typically demonstrate reduced penetrance, variable
      expressivity, and until recently have been exclusively identified in families
      with anosmia. The purpose of this study was to determine whether FGFR1 mutations
      were present in a unique family with autosomal dominant, fully penetrant,
      normosmic IHH. DESIGN: The study is a review of detailed clinical findings,
      dynamic endocrine studies, and performance of a molecular analysis of the FGFR1
      gene. SETTING: The study was carried out in an academic medical center. PATIENTS:
      All four affected individuals have complete IHH with full penetrance but no
      anosmia/hyposmia, and they have none of the FGFR1-associated anomalies. In
      addition, no other family member has anosmia. Inverventions: Interventions
      included detailed phenotype characterization including history, physical exam,
      smell testing, dynamic pituitary testing, brain imaging, and molecular analysis.
      MAIN OUTCOME MEASURES: Outcome was measured by the determination of the severity
      of IHH, olfactory function, and sequence of the FGFR1 gene. RESULTS: The same
      heterozygous nonsense mutation, Arg622X, was present in all four affected
      members, but not in three unaffected members or 100 controls. The mutation is
      predicted to encode a truncated protein or result in nonsense-mediated decay.
      CONCLUSIONS: Our findings indicate that mutations in the FGFR1 gene can cause
      normosmic, fully penetrant, complete IHH with little or no variable expressivity,
      and without the other FGFR1-associated anomalies typically found in KS.

PMID- 17200177
TI  - Alternative vascularization mechanisms in cancer: Pathology and therapeutic
      implications.
AB  - Although cancer cells are not generally controlled by normal regulatory
      mechanisms, tumor growth is highly dependent on the supply of oxygen, nutrients,
      and host-derived regulators. It is now established that tumor vasculature is not
      necessarily derived from endothelial cell sprouting; instead, cancer tissue can
      acquire its vasculature by co-option of pre-existing vessels, intussusceptive
      microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis, or
      vasculogenic mimicry. The best-known molecular pathway driving tumor
      vascularization is the hypoxia-adaptation mechanism. However, a broad and diverse
      spectrum of genetic aberrations is associated with the development of the
      "angiogenic phenotype." Based on this knowledge, novel forms of antivascular
      modalities have been developed in the past decade. When applying these targeted
      therapies, the stage of tumor progression, the type of vascularization of the
      given cancer tissue, and the molecular machinery behind the vascularization
      process all need to be considered. A further challenge is finding the most
      appropriate combinations of antivascular therapies and standard radio- and
      chemotherapies. This review intends to integrate our recent knowledge in this
      field into a rational strategy that could be the basis for developing effective
      clinical modalities using antivascular therapy for cancer.

PMID- 17200178
TI  - Linking selective vulnerability to cell death mechanisms in Parkinson's disease.

PMID- 17200180
TI  - Persistent Chlamydia pneumoniae infection of cardiomyocytes is correlated with
      fatal myocardial infarction.
AB  - Acute myocardial infarction (AMI) associated with unfavorable prognosis is likely
      to be the consequence of a diffuse active chronic inflammatory process that
      destabilizes the whole coronary tree and myocardium, suggesting a possible common
      causal agent underlying both conditions. The main objective of this study was to
      investigate whether Chlamydia pneumoniae (CP) infection occurred beyond the
      coronary plaques, namely in the myocardium of individuals who died of AMI. The
      presence of CP cell wall antigen (OMP-2) and CP-HSP60 was investigated in the
      myocardium and coronary plaques of 10 AMI and 10 age-matched control patients by
      immunohistochemistry, electron microscopy, and molecular biology. OMP-2 antigens
      were found in the unaffected myocardium of 9 of 10 AMI patients. Conversely, only
      1 of 10 control patients exhibited a positive staining for CP. Moreover, OMP-2
      and CP-HSP60 were detected in the whole coronary tree. CP presence was strongly
      associated with a T-cell inflammatory infiltrate. Our results suggest that CP may
      underlie both coronary and myocardial vulnerabilities in patients who died of AMI
      and corroborate the notion that CP may act by reducing cardiac reserves, thus
      worsening the ischemic burden of myocardium.

PMID- 17200179
TI  - Distinctive epidermal growth factor receptor/extracellular regulated kinase
      independent and -dependent signaling pathways in the induction of airway mucin 5B
      and mucin 5AC expression by phorbol 12-myristate 13-acetate.
AB  - Elevated expression of gel-forming mucin (MUC) genes MUC5AC and MUC5B is a major
      pathological feature in various airway diseases. In this study, we show that
      phorbol 12-myristate 13-acetate (PMA) is a potent stimulator for MUC5B gene
      expression under air-liquid interface conditions in three airway epithelial cell
      systems: primary cultures of normal human bronchial epithelial cells, the
      immortalized normal bronchial epithelial cell line HBE1, and the human lung
      adenocarcinoma cell line A549. Stimulation was time- and dose-dependent, could be
      demonstrated by promoter-reporter gene transfection, and was sensitive to
      mithramycin A, suggesting the involvement of a specificity protein 1-based
      transcriptional mechanism in the stimulation. PMA-induced MUC5B message and
      promoter-reporter gene activity were specifically sensitive to inhibition of
      protein kinase C delta, which was further confirmed by the forced expression of
      dominant-negative mutant of protein kinase C delta. Regarding downstream
      transduction, PMA-induced MUC5B expression was sensitive to inhibitors and
      dominant-negative expression of signaling molecules involved in Ras/mitogen
      activated protein kinase/extracellular signal-regulated kinase kinase kinase1
      mediated c-Jun N-terminal kinase and p38 pathways. This contrasted with the
      inhibition of PMA-induced MUC5AC expression by inhibitors of the Ras/epidermal
      growth factor receptor/extracellular regulated kinase signaling pathway. These
      results demonstrate for the first time that PMA-stimulated MUC5AC and MUC5B
      expressions are regulated through distinctive epidermal growth factor
      receptor/extracellular regulated kinase-dependent and -independent signaling
      pathways.

PMID- 17200181
TI  - B-cell epitope spreading is a critical step for the switch from C-protein-induced
      myocarditis to dilated cardiomyopathy.
AB  - Repeated inflammation in the heart is one of the initiation factors of dilated
      cardiomyopathy (DCM). In a previous study, we established a new animal model for
      DCM by immunization of rats with recombinant cardiac C-protein fragment 2 (CC2).
      The present study examined factors involved in the development of DCM. Analysis
      using overlapping peptides revealed that the major carditogenic epitope resides
      only in the residue 615-647 [CC2 peptide 12 (CC2P12)]. However, immunization with
      CC2P12 induced moderate inflammation without subsequent DCM. CDR3 spectratyping
      analysis of the T-cell repertoire demonstrated that Vbeta4-positive T cells were
      preferentially expanded in both CC2- and CC2P12-immunized rats. Although there
      was no significant difference in the T-cell characteristics, examinations of the
      B-cell epitope revealed that marked epitope spreading occurred in CC2-immunized
      but not CC2P12-immunized rats from 4 weeks after immunization. Consistent with
      this finding, immunization with CC2P12 and simultaneous transfer of anti-peptide
      antisera induced significantly more severe inflammation and fibrosis than CC2P12
      immunization alone. However, the transfer of the antisera without CC2P12
      immunization did not induce any pathology. These findings suggest that T-cell
      activation and B-cell epitope spreading in the CC2 molecule is a key step for the
      switch from myocarditis to the development of DCM.

PMID- 17200182
TI  - Alternative complement pathway in the pathogenesis of disease mediated by anti
      neutrophil cytoplasmic autoantibodies.
AB  - Clinical and experimental data indicate that anti-neutrophil cytoplasmic
      autoantibodies (ANCAs) cause glomerulonephritis and vasculitis. Here we report
      the first evidence that complement is an important mediator of ANCA disease.
      Transfer of anti-myeloperoxidase (MPO) IgG into wild-type mice or anti-MPO
      splenocytes into immune-deficient mice caused crescentic glomerulonephritis that
      could be completely blocked by complement depletion. The role of specific
      complement activation pathways was investigated using mice with knockout of the
      common pathway component C5, classic and lectin binding pathway component C4, and
      alternative pathway component factor B. After injection of anti-MPO IgG, C4-/-
      mice developed disease comparable with wild-type disease; however, C5-/- and
      factor B-/- mice developed no disease. To substantiate a role for complement in
      human ANCA disease, IgG was isolated from patients with myeloperoxidase ANCA (MPO
      ANCA) or proteinase 3 ANCA (PR3-ANCA) and from controls. Incubation of MPO-ANCA
      or PR3-ANCA IgG with human neutrophils caused release of factors that activated
      complement. IgG from healthy controls did not produce this effect. The findings
      suggest that stimulation of neutrophils by ANCA causes release of factors that
      activate complement via the alternative pathway, thus initiating an inflammatory
      amplification loop that mediates the severe necrotizing inflammation of ANCA
      disease.

PMID- 17200183
TI  - Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary
      fibrosis.
AB  - Neutrophil elastase is a serine protease stored in the azurophilic granules of
      leukocytes. It has been implicated in the pathology of several lung diseases and
      is generally presumed to contribute to the tissue destruction and extracellular
      matrix damage associated with these conditions. To delineate the role of
      neutrophil elastase in pulmonary inflammation and fibrosis, neutrophil elastase
      null mice were intratracheally instilled with bleomycin. In neutrophil elastase
      null mice, biochemical and morphological characteristics of pulmonary fibrosis
      were attenuated for at least 60 days after bleomycin administration despite a
      typical response to bleomycin as evidenced by assessment of indices of DNA and
      cell damage. Neutrophil burden of bleomycin-treated wild-type and neutrophil
      elastase-null mice was comparable, and marked neutrophilic alveolitis was
      manifest in bleomycin-treated neutrophil elastase-null mice. An absence of
      immunostaining for active transforming growth factor (TGF)-beta in lung tissue
      from bleomycin-treated neutrophil elastase-null mice suggested a defect in TGF
      beta activation, which was confirmed by biochemical assessment of TGF-beta levels
      in bronchoalveolar lavage fluid and lung tissue. These data point to novel and
      unexpected fibrogenic consequences of neutrophil elastase activity in the
      inflamed lung.

PMID- 17200185
TI  - Lack of endothelial nitric-oxide synthase leads to progressive focal renal
      injury.
AB  - Because endothelial nitric-oxide synthase (eNOS) is generally considered
      protective against renal injury, we examined eNOS knockout mice for kidney
      pathology. In 80% of the adults examined, the renal surface was marked by
      distinct indented scars containing crowded small glomeruli but lacking attached
      tubules. Although vasculature was intact in the scars, Bowman's space was dilated
      and glomerular tufts were degenerated. The atubular glomeruli were embedded in a
      dense interstitial matrix composed of cells positive for fibroblast (FSP-1) or
      macrophage (F4/80) markers, degenerated proximal tubules and collecting ducts,
      and diffuse fibrotic deposits. Surrounding regions of kidney contained mostly
      normal-appearing tubules, but enlarged or sclerotic glomeruli were also present.
      In neonatal animals, apoptosis and necrosis were concentrated in tubules within
      focal parenchymal zones, with narrowing of the glomerulotubular "neck." In
      summary, targeted deletion of eNOS in mice leads to progressive focal renal
      abnormalities, including glomerular hypoplasia, and tubular cell death, leading
      to separation of glomeruli from tubules and tubular disruption. These
      abnormalities begin developing during the normal up-regulation of eNOS in the
      maturing kidney and are similar to those of a variety of chronic renal disorders.
      Endogenous renal eNOS production therefore seems critical for the maintenance of
      nephron maturation and integrity.

PMID- 17200184
TI  - Regulation of autophagy by extracellular signal-regulated protein kinases during
      1-methyl-4-phenylpyridinium-induced cell death.
AB  - Increased autophagic vacuoles (AVs) occur in injured or degenerating neurons,
      under both developmental and pathological situations. Although regulation of
      starvation-induced autophagy has been extensively studied, less is known about
      autophagic responses to pathological damage. The neurotoxin 1-methyl-4
      phenylpyridinium (MPP(+)) produces mitochondria-targeted injury, which
      contributes to parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydro
      pyridine in mammals. Here, we demonstrate that MPP(+) elicited increased
      autophagy in SH-SY5Y cells, as assessed by electron microscopy,
      immunofluorescence for the autophagy protein LC3/Atg8, LC3 electrophoretic
      mobility shift, mitochondrial degradation, and monodansylcadaverine staining for
      late AVs/autolysosomes. During nutrient deprivation, class III
      phosphatidylinositol-3 kinase (PI3K) stimulates autophagy in concert with the
      autophagy-regulatory protein beclin 1/Atg6. Although PI3K inhibitors and RNA
      interference knockdown of beclin 1 effectively inhibited autophagy elicited by
      amino acid deprivation, neither reduced MPP+-induced autophagic stress. In
      contrast, inhibition of mitogen-activated protein kinase/extracellular signal
      regulated protein kinase kinase reduced AV content, mitochondrial degradation,
      and cell death in MPP+-treated cells. RNA interference studies targeting core Atg
      proteins also reduced AV content and cell death. Likewise, in primary midbrain
      dopaminergic neurons, MPP+ elicited increased AV content, which was reversed by
      inhibition of mitogen-activated protein kinase/extracellular signal-regulated
      protein kinase kinase but not PI3K. These results implicate a role for
      extracellular signal-regulated protein kinase (ERK) signaling upstream of MPP+
      elicited autophagic stress. Moreover, pathological stimulation of beclin 1
      independent autophagy is associated with neuronal cell death.

PMID- 17200187
TI  - Alphav beta6 integrin regulates renal fibrosis and inflammation in Alport mouse.
AB  - The transforming growth factor (TGF)-beta-inducible integrin alpha v beta6 is
      preferentially expressed at sites of epithelial remodeling and has been shown to
      bind and activate latent precursor TGF-beta. Herein, we show that alpha v beta6
      is overexpressed in human kidney epithelium in membranous glomerulonephritis,
      diabetes mellitus, IgA nephropathy, Goodpasture's syndrome, and Alport syndrome
      renal epithelium. To assess the potential regulatory role of alpha v beta6 in
      renal disease, we studied the effects of function-blocking alpha v beta6
      monoclonal antibodies (mAbs) and genetic ablation of the beta6 subunit on kidney
      fibrosis in Col4A3-/- mice, a mouse model of Alport syndrome. Expression of alpha
      v beta6 in Alport mouse kidneys was observed primarily in cortical tubular
      epithelial cells and in correlation with the progression of fibrosis. Treatment
      with alpha v beta6-blocking mAbs inhibited accumulation of activated fibroblasts
      and deposition of interstitial collagen matrix. Similar inhibition of renal
      fibrosis was observed in beta6-deficient Alport mice. Transcript profiling of
      kidney tissues showed that alpha v beta6-blocking mAbs significantly inhibited
      disease-associated changes in expression of fibrotic and inflammatory mediators.
      Similar patterns of transcript modulation were produced with recombinant soluble
      TGF-beta RII treatment, suggesting shared regulatory functions of alpha v beta6
      and TGF-beta. These findings demonstrate that alpha v beta6 can contribute to the
      regulation of renal fibrosis and suggest this integrin as a potential therapeutic
      target.

PMID- 17200186
TI  - Aggregated myocilin induces russell bodies and causes apoptosis: implications for
      the pathogenesis of myocilin-caused primary open-angle glaucoma.
AB  - Primary open-angle glaucoma with elevated intraocular pressure is a leading cause
      of blindness worldwide. Mutations of myocilin are known to play a critical role
      in the manifestation of the disease. Misfolded mutant myocilin forms secretion
      incompetent intracellular aggregates. The block of myocilin secretion was
      proposed to alter the extracellular matrix environment of the trabecular
      meshwork, with subsequent impediment of aqueous humor outflow leading to elevated
      intraocular pressure. However, the molecular pathogenesis of myocilin-caused
      glaucoma is poorly defined. In this study, we show that heteromeric complexes
      composed of wild-type and mutant myocilin were retained in the rough endoplasmic
      reticulum, aggregating to form inclusion bodies typical of Russell bodies. The
      presence of myocilin aggregates induced the unfolded protein response proteins
      BiP and phosphorylated endoplasmic reticulum-localized eukaryotic initiation
      factor-2alpha kinase (PERK) with the subsequent activation of caspases 12 and 3
      and expression of C/EBP homologous protein (CHOP)/GADD153, leading to apoptosis.
      Our findings identify endoplasmic reticulum stress-induced apoptosis as a pathway
      to explain the reduction of trabecular meshwork cells in patients with myocilin
      caused glaucoma. As a consequence, the phagocytotic capacity of the remaining
      trabecular meshwork cell population would be insufficient for effective cleaning
      of aqueous humor, constituting a major pathogenetic factor for the development of
      increased intraocular pressure in primary open-angle glaucoma.

PMID- 17200188
TI  - Expression of the metastasis suppressor KAI1 in decidual cells at the human
      maternal-fetal interface: Regulation and functional implications.
AB  - At the human maternal-fetal interface, the decidua forms a dense matrix that is
      believed to limit trophoblast invasion. We investigated whether the metastasis
      suppressor KAI1 (CD82) is expressed at the maternal-fetal interface.
      Immunohistochemistry showed strong expression of KAI1 in decidual cells, whereas
      trophoblast cells were negative for KAI1. In luteal phase endometrium, KAI1 was
      present in decidualizing endometrial stromal cells. We investigated whether KAI1
      expression in endometrial stromal cells is regulated by the decidualizing stimuli
      cAMP and progesterone or by the cytokine interleukin (IL)-1beta. Western blot
      analysis revealed induction of KAI1 protein by cAMP analog, but not by
      progesterone, in a delayed fashion. In contrast, IL-1beta rapidly stimulated KAI1
      expression at the transcript level and at the protein level. Cultured decidual
      cells from term placenta expressed a basal level of KAI1 protein that was
      elevated on cAMP stimulation. Silencing of KAI1 by RNA interference attenuated
      expression of decorin, a decidual product implicated in limiting trophoblast
      invasion. This study shows for the first time the expression of KAI1 in decidual
      cells at the human maternal-fetal interface, where the metastasis suppressor
      might participate in intercellular communication with trophoblast cells and the
      control of trophoblast invasion.

PMID- 17200189
TI  - Asbestos-induced peribronchiolar cell proliferation and cytokine production are
      attenuated in lungs of protein kinase C-delta knockout mice.
AB  - The signaling pathways leading to the development of asbestos-associated diseases
      are poorly understood. Here we used normal and protein kinase C (PKC)-delta
      knockout (PKCdelta-/-) mice to demonstrate multiple roles of PKC-delta in the
      development of cell proliferation and inflammation after inhalation of chrysotile
      asbestos. At 3 days, asbestos-induced peribronchiolar cell proliferation in wild
      type mice was attenuated in PKCdelta-/- mice. Cytokine profiles in
      bronchoalveolar lavage fluids showed increases in interleukin (IL)-1beta, IL-4,
      IL-6, and IL-13 that were decreased in PKCdelta-/- mice. At 9 days, microarray
      and quantitative reverse transcriptase-polymerase chain reaction analysis of lung
      tissues revealed increased mRNA levels of the profibrotic cytokine, IL-4, in
      asbestos-exposed wild-type mice but not PKCdelta-/- mice. PKCdelta-/- mice also
      exhibited decreased lung infiltration of polymorphonuclear cells, natural killer
      cells, and macrophages in bronchoalveolar lavage fluid and lung, as well as
      increased numbers of B lymphocytes and plasma cells. These changes were
      accompanied by elevated mRNA levels of immunoglobulin chains. These data show
      that modulation of PKC-delta has multiple effects on peribronchiolar cell
      proliferation, proinflammatory and profibrotic cytokine expression, and immune
      cell profiles in lung. These results also implicate targeted interruption of PKC
      delta as a potential therapeutic option in asbestos-induced lung diseases.

PMID- 17200190
TI  - Pre-B-cell leukemia transcription factor 1 regulates expression of valosin
      containing protein, a gene involved in cancer growth.
AB  - Valosin-containing protein (VCP) is involved in a wide variety of cellular
      functions. Our previous studies showed that the enhanced expression of VCP in
      cancer cells correlated with invasion and metastasis of cancers. Here, the
      regulatory mechanism for VCP transcription was investigated. Luciferase reporter
      constructs containing serially deleted 5'-flanking region of the VCP gene were
      transfected into MCF7 mammary carcinoma cell line, in which VCP was abundantly
      expressed. The deletion and mutation at the two binding motifs for pre-B-cell
      leukemia transcription factor 1 (PBX1) reduced the luciferase activity,
      indicating that these two PBX1 motifs mediated the transactivation of the VCP
      gene. Chromatin immunoprecipitation assay showed the binding of PBX-1 to the 5'
      flanking region of the VCP gene. The knockdown of PBX1 by siRNA decreased the
      expression level of VCP. VCP is reported to maintain cell viability after the
      treatment of tumor necrosis factor-alpha. The viability of tumor necrosis factor
      alpha-treated cells was significantly reduced in PBX1 knockdown MCF7. These
      findings indicate that PBX1 plays a crucial role in VCP expression and function
      and that the PBX-VCP pathway might be important for cell survival under cytokine
      stress.

PMID- 17200191
TI  - Lack of noggin expression by cancer cells is a determinant of the osteoblast
      response in bone metastases.
AB  - Prostate and mammary cancer bone metastases can be osteoblastic or osteolytic,
      but the mechanisms determining these features are unclear. Bone morphogenetic and
      Wnt proteins are osteoinductive molecules. Their activity is modulated by
      antagonists such as noggin and dickkopf-1. Differential expression analysis of
      bone morphogenetic and Wnt protein antagonists in human prostate and mammary
      cancer cell lines showed that osteolytic cell lines constitutively express in
      vitro noggin and dickkopf-1 and at least one of the osteolytic cytokines
      parathyroid hormone-related protein, colony-stimulating factor-1, and interleukin
      8. In contrast, osteoinductive cell lines express neither noggin nor dickkopf-1
      nor osteolytic cytokines in vitro. The noggin differential expression profile
      observed in vitro was confirmed in vivo in prostate cancer cell lines xenografted
      into bone and in clinical samples of bone metastasis. Forced noggin expression in
      an osteoinductive prostate cancer cell line abolished the osteoblast response
      induced in vivo by its intraosseous xenografts. Basal bone resorption and tumor
      growth kinetics were marginally affected. Lack of noggin and possibly dickkopf-1
      expression by cancer cells may be a relevant mechanism contributing to the
      osteoblast response in bone metastases. Concomitant lack of osteolytic cytokines
      may be permissive of this effect. Noggin is a candidate drug for the adjuvant
      therapy of bone metastasis.

PMID- 17200192
TI  - Identification and functional characterization of the hepatic stellate cell CD38
      cell surface molecule.
AB  - The activation of hepatic stellate cells (HSCs) is a critical event in hepatic
      fibrosis, because these cells are the main producers of extracellular matrix
      proteins in the liver and contribute to the modulation of inflammatory responses
      via the secretion of several cytokines and the expression of adhesion molecules.
      The goal of the present study was to characterize cell surface proteins that
      regulate HSC activation. To this end, a panel of monoclonal antibodies (mAbs) was
      generated. mAb 14.27 recognized a protein of 45 kd that was highly expressed on
      HSCs. Affinity purification of this protein followed by sequencing revealed that
      protein to be CD38. We subsequently demonstrated that CD38 was constitutively
      expressed by HSCs and that its expression increased after in vitro and in vivo
      activation. mAb 14.27 induced an increase in cytosolic Ca2+ levels in HSCs,
      showing that it functions as an agonistic antibody. Moreover, the effects
      mediated by the CD38 mAb included induction of the proinflammatory cytokine
      interleukin-6 and up-regulation of the adhesion molecules intercellular adhesion
      molecule-1, vascular cell adhesion molecule-1, and neural cell adhesion molecule.
      Collectively, our data suggest that CD38 can act as a regulator of HSC activation
      and effector functions.

PMID- 17200193
TI  - Accelerated wound closure in mice deficient for interleukin-10.
AB  - The impact of the local inflammatory response on the process of wound healing has
      been debated for decades. In particular, the question whether infiltrating
      macrophages and granulocytes promote or impede tissue repair has received much
      attention. In the present study, we show that wound healing is accelerated in
      mice deficient for the anti-inflammatory cytokine interleukin (IL)-10. IL-10-/-
      mice closed excisional wounds significantly earlier compared with IL-10-competent
      control littermates. This effect was attributable to accelerated
      epithelialization as well as enhanced contraction of the wound tissue in the
      mutant animals. Increased alpha-smooth muscle actin expression in IL-10-deficient
      mice suggests that augmented myofibroblast differentiation is responsible for the
      enhanced contraction of wounds in mutant mice. The number of macrophages
      infiltrating the wound tissue was significantly increased in IL-10-/- mice
      compared with control littermates suggesting that this cell type mediates the
      accelerated tissue repair. These results show for the first time that IL-10 can
      impede wound repair.

PMID- 17200195
TI  - Contrasting roles for axonal degeneration in an autoimmune versus viral model of
      multiple sclerosis: When can axonal injury be beneficial?
AB  - Although demyelination is a cardinal feature in multiple sclerosis, axonal injury
      also occurs. We tested whether a delay in axonal degeneration could affect the
      disease severity in two models for multiple sclerosis: experimental autoimmune
      encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus (TMEV)
      infection. We compared wild-type C57BL/6 (B6) mice with C57BL/Wld(s) (Wld) mice,
      which carry a mutation that delays axonal degeneration. In EAE, both mouse
      strains were sensitized with myelin oligodendrocyte glycoprotein (MOG)(35-55)
      peptide and showed a similar disease onset, MOG-specific lymphoproliferative
      responses, and inflammation during the acute stage of EAE. However, during the
      chronic stage, B6 mice continued to show paralysis with a greater extent of
      axonal damage, demyelination, and MOG-specific lymphoproliferative responses
      compared with Wld mice, which showed complete recovery. In TMEV infection, only
      Wld mice were paralyzed and had increased inflammation, virus antigen-positive
      cells, and TMEV-specific lymphoproliferative responses versus infected B6 mice.
      Because TMEV can use axons to disseminate in the brain, axonal degeneration in B6
      mice might be a beneficial mechanism that limits the virus spread, whereas slow
      axonal degeneration in Wld mice could favor virus spread. Therefore, axonal
      degeneration plays contrasting roles (beneficial versus detrimental) depending on
      the initiator driving the disease.

PMID- 17200194
TI  - Th1 immune response promotes severe bone resorption caused by Porphyromonas
      gingivalis.
AB  - Bacterial infections of the dental pulp result in soft tissue and alveolar bone
      destruction. It has been suggested that Th1 responses promote disease, whereas
      Th2 responses are protective. However, other studies have challenged this notion.
      To address this question, bone destruction was evaluated in mice immunized to
      develop strong and polarized Th1- or Th2-biased responses to the oral pathogen
      Porphyromonas gingivalis. Th1 bias was confirmed by the presence of high titers
      of serum IgG2a and the production of high levels of interferon (IFN)-gamma and no
      interleukin (IL)-4 by lymph node cells stimulated with P. gingivalis antigens. In
      contrast, Th2-biased animals had high titer IgG1 and no IgG2a, and their lymph
      node cells produced high levels of IL-4 but no IFN-gamma. Subsequent infection of
      the dental pulp with P. gingivalis caused extensive inflammation and alveolar
      bone destruction in Th1-biased mice, whereas Th2-biased mice and controls
      developed minimal lesions. Inflammatory granulomas in Th1-biased mice were
      heavily infiltrated with osteoclasts and had high local expression of IFN-gamma,
      IL-1alpha, and IL-1beta. Little or no IFN-gamma/IL-1alpha/IL-1beta and no obvious
      osteoclasts were detected in lesions of Th2-biased and control groups. These
      results directly demonstrate that specific Th1 responses promote severe infection
      stimulated alveolar bone loss.

PMID- 17200196
TI  - FasL and TRAIL induce epidermal apoptosis and skin ulceration upon exposure to
      Leishmania major.
AB  - Receptor-mediated apoptosis is proposed as an important regulator of keratinocyte
      homeostasis in human epidermis. We have previously reported that Fas/FasL
      interactions in epidermis are altered during cutaneous leishmaniasis (CL) and
      that keratinocyte death through apoptosis may play a pathogenic role for skin
      ulceration. To further investigate the alterations of apoptosis during CL, a
      keratinocyte cell line (HaCaT) and primary human epidermal keratinocytes were
      incubated with supernatants from Leishmania major-infected peripheral blood
      mononuclear cells. An apoptosis-specific microarray was used to assess mRNA
      expression in HaCaT cells exposed to supernatants derived from L. major-infected
      cultures. Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      mRNA and protein expression were significantly up-regulated, and apoptosis was
      detected in both HaCaT and human epidermal keratinocyte cells. The keratinocyte
      apoptosis was partly inhibited through blocking of Fas or FasL and even more
      efficiently through TRAIL neutralization. Up-regulation of Fas on keratinocytes
      in epidermis and the presence of FasL-expressing macrophages and T cells in
      dermis were previously reported by us. In this study, keratinocytes expressing
      TRAIL, as well as the proapoptotic receptor TRAIL-R2, were detected in skin
      biopsies from CL cases. We propose that activation of Fas and TRAIL apoptosis
      pathways, in the presence of inflammatory mediators at the site of infection,
      leads to tissue destruction and ulceration during CL.

PMID- 17200197
TI  - Islet beta-cell-specific T cells can use different homing mechanisms to
      infiltrate and destroy pancreatic islets.
AB  - Organ infiltration by T cells depends on the adhesion molecules expressed in
      these sites and on homing receptors expressed by the T cells. Here, we have
      studied which form of priming can enable T cells to home to pancreatic islets. To
      this end, we have used transgenic mice expressing the model autoantigen ovalbumin
      in pancreatic islets and transgenic ovalbumin-specific CD4 and CD8 T cells. We
      demonstrate that these T cells were imprinted with homing receptor patterns
      characteristic for the site of priming, such as alpha4beta7 integrin for mucosal
      antigen delivery or functionally active alpha4beta1 integrin for islet
      autoantigens. The adhesion molecules corresponding to these receptors were found
      to be constitutively expressed in islets, enabling T cells bearing these
      receptors to infiltrate the islets and to cause diabetes. Disease was prevented
      only by blockade of the endothelial adhesion molecule, ligand of homing receptors
      with which the T cells were imprinted. Thus, different priming locations induced
      different homing mechanisms, allowing T cells to target the islets. This may
      contribute to the susceptibility of islets to T-cell-mediated attack.
      Furthermore, it may pertain to the design of adhesion-modulating therapies alone
      or in combination with external autoantigen administration.

PMID- 17200198
TI  - Role of interleukin 10 during persistent infection with the relapsing fever
      Spirochete Borrelia turicatae.
AB  - Relapsing fever is an infection characterized by peaks of spirochetemia
      attributable to antibody selection against variable serotypes. In the absence of
      B cells, serotypes cannot be cleared, resulting in persistent infection. We
      previously identified differences in spirochetemia and disease severity during
      persistent infection of severe combined immunodeficiency mice with isogenic
      serotypes 1 (Bt1) or 2 (Bt2) of Borrelia turicatae. To investigate this further,
      we studied pathogen load, clinical disease, cytokine/chemokine production, and
      inflammation in mice deficient in B (Igh6-/-) or B and T (Rag1-/-) cells
      persistently infected with Bt1 or Bt2. The results showed that Igh6-/- mice,
      despite lower spirochetemia, had a significantly aggravated disease course
      compared with Rag1-/- mice. Measurement of cytokines revealed a significant
      positive correlation between pathogen load and interleukin (IL)-10 in blood,
      brain, and heart. Bt2-infected Rag1-/- mice harbored the highest spirochetemia
      and, at the same time, displayed the highest IL-10 plasma levels. In the brain,
      Bt1, which was five times more neurotropic than Bt2, caused higher IL-10
      production. Activated microglia were the main source of IL-10 in brain. IL-10
      injected systemically reduced disease and spirochetemia. The results suggest IL
      10 plays a protective role as a down-regulator of inflammation and pathogen load
      during infection with relapsing fever spirochetes.

PMID- 17200199
TI  - Adrenomedullin protects from experimental arthritis by down-regulating
      inflammation and Th1 response and inducing regulatory T cells.
AB  - Rheumatoid arthritis is a chronic autoimmune disease of unknown etiology
      characterized by chronic inflammation in the joints and subsequent destruction of
      the cartilage and bone. The present study proposes a new strategy for the
      treatment of arthritis: the administration of the immunomodulatory neuropeptide
      adrenomedullin. Treatment with adrenomedullin significantly reduced incidence and
      severity of collagen-induced arthritis, an experimental model of rheumatoid
      arthritis, completely abrogating joint swelling and destruction of cartilage and
      bone. The therapeutic effect of adrenomedullin was associated with a striking
      reduction of the two deleterious components of the disease, ie, the Th1-driven
      autoimmune and inflammatory responses. Adrenomedullin also induced the generation
      and/or activation of efficient CD4+ CD25+ regulatory T cells in arthritis with
      capacity to suppress autoreactive response and restore immune tolerance, which
      could play a pivotal role in the therapeutic effect of adrenomedullin on
      experimental arthritis contributing to the restoration of immune tolerance.

PMID- 17200200
TI  - Soluble mannosylated myelin peptide inhibits the encephalitogenicity of
      autoreactive T cells during experimental autoimmune encephalomyelitis.
AB  - We have previously shown that immunization with a mannosylated myelin peptide in
      complete adjuvant induces tolerance instead of disease in experimental autoimmune
      encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we
      demonstrate that treatment with a soluble mannosylated epitope of proteolipid
      protein (M-PLP(139-151)) significantly inhibits disease mediated by autoreactive
      myelin-specific T cells during EAE. Treatment with M-PLP(139-151), applied in
      different EAE models, significantly reduced the incidence of disease and the
      severity of clinical symptoms. Delayed-type hypersensitivity responses were
      abolished after peptide treatment, emphasizing the impact on peripheral T-cell
      reactivity. Histological analysis of spinal cord tissue from mice treated with M
      PLP(139-151) revealed the presence of only few macrophages and T cells. Moreover,
      little expression of interferon-gamma, interleukin-23, or major
      histocompatibility complex class II antigen was detected. Immune modulation by M
      PLP(139-151) was primarily antigen-specific because an irrelevant mannosylated
      peptide showed no significant effect on delayed-type hypersensitivity responses
      or on the course of EAE. Therefore, mannosylated antigens may represent a novel
      therapeutic approach for antigen-specific modulation of autoreactive T cells in
      vivo.

PMID- 17200201
TI  - Immunomodulator FTY720 induces myofibroblast differentiation via the
      lysophospholipid receptor S1P3 and Smad3 signaling.
AB  - The novel immunomodulator FTY720 is an effective immunosuppressive agent in
      experimental models of transplantation and autoimmunity and is currently
      undergoing phase III clinical trials for multiple sclerosis. Phosphorylated
      FTY720 is a structural analogue of sphingosine 1-phosphate (S1P) and therefore
      acts as a high-affinity agonist at four of the five G protein-coupled S1P
      receptors. It has been well established that there exists a crosstalk between S1P
      and transforming growth factor (TGF)-beta signaling. Because TGF-beta is the most
      prominent inductor of fibrosis and myofibroblasts are primarily responsible for
      excessive matrix protein formation, we examined whether FTY720, in analogy to TGF
      beta, induces differentiation of fibroblasts into myofibroblasts. Indeed, FTY720
      provoked myofibroblast differentiation comparable with that of TGF-beta. For
      biological efficacy, FTY720 required endogenous phosphorylation because
      inhibition of sphingosine kinase completely prevented FTY720 from inducing the
      differentiation process. Moreover, we identified the lysophospholipid receptor
      S1P3 as the crucial receptor subtype for FTY720-induced myofibroblast
      differentiation because the effect was abolished in fibroblasts isolated from
      S1P3 knockout mice. Finally, we determined that downstream of S1P3 signaling
      Smad3 activation is essential for myofibroblast differentiation in response to
      FTY720. Thus, FTY720 may have adverse fibrotic effects related to its activity on
      S1P3 signaling.

PMID- 17200202
TI  - Unique matrix structure in the rough endoplasmic reticulum cisternae of
      pseudoachondroplasia chondrocytes.
AB  - Mutations in cartilage oligomeric matrix protein (COMP) cause two skeletal
      dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia
      (MED/EDM1). Because COMP exists as a homopentamer, only one mutant COMP subunit
      may result in an abnormal complex that is accumulated in expanded rough
      endoplasmic reticulum (rER) cisternae, a hallmark of PSACH. Type IX collagen and
      matrilin-3 (MATN3), also accumulate in the rER cisternae of PSACH chondrocytes,
      but it is unknown how mutant COMP interacts with these proteins. The studies
      herein focus on defining the organization of these intracellularly retained
      proteins using fluorescence deconvolution microscopy. A unique matrix
      organization was identified in which type II procollagen formed a central core
      surrounded by a protein network of mutant COMP, type IX collagen, and MATN3. This
      pattern of matrix organization was found in multiple cisternae from single
      chondrocytes and in chondrocytes with different COMP mutations, indicating a
      common pattern of interaction. This suggests that stalling of mutant COMP and an
      interaction between mutant COMP and type II procollagen are initiating events in
      the assembly of matrix in the rER, possibly explaining why the material is not
      readily cleared from the rER. Altogether, these data suggest that mutant COMP
      initiates and perhaps catalyzes premature intracellular matrix assembly.

PMID- 17200204
TI  - Caveolin-1(-/-)- and caveolin-2(-/-)-deficient mice both display numerous
      skeletal muscle abnormalities, with tubular aggregate formation.
AB  - Here, we examine the role of "non-muscle" caveolins (Cav-1 and Cav-2) in skeletal
      muscle biology. Our results indicate that skeletal muscle fibers from male Cav-1(
      /-) and Cav-2(-/-) mice show striking abnormalities, such as tubular aggregates,
      mitochondrial proliferation/aggregation, and increased numbers of M-cadherin
      positive satellite cells. Notably, these skeletal muscle defects were more
      pronounced with increasing age. Because Cav-2-deficient mice displayed normal
      expression levels of Cav-1, whereas Cav-1-null mice exhibited an almost complete
      deficiency in Cav-2, these skeletal muscle abnormalities seem to be due to loss
      of Cav-2. Thus, Cav-2(-/-) mice represent a novel animal model-and the first
      genetically well-defined mouse model-that can be used to study the pathogenesis
      of tubular aggregate formation, which remains a poorly understood age-related
      skeletal muscle abnormality. Finally, because Cav-1 and Cav-2 were not expressed
      within mature skeletal myofibers, our results indicate that development of these
      abnormalities probably originates in stem/precursor cells, such as satellite
      cells or myoblasts. Consistent with this hypothesis, skeletal muscle isolated
      from male Cav-3(-/-) mice did not show any of these abnormalities. As such, this
      is the first study linking stem cells with the genesis of these intriguing muscle
      defects.

PMID- 17200203
TI  - Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin
      like growth factor-I receptor and Mammalian target of rapamycin.
AB  - Decorin, a small leucine-rich proteoglycan, affects the synthesis of the elastic
      fiber component fibrillin-1 in the kidney via hitherto unknown mechanisms. Here,
      we show that decorin binds to and induces phosphorylation of insulin-like growth
      factor-I (IGF-I) receptor in renal fibroblasts. Inhibition of the IGF-I receptor
      tyrosine kinase and its downstream target phosphoinositide-3 kinase prevented
      decorin-mediated synthesis of fibrillin-1. Furthermore, decorin induced
      phosphorylation of phosphoinositide-dependent kinase 1, protein kinase B/Akt,
      mammalian target of rapamycin (mTOR), and p70 S6 kinase. Accordingly, the
      enhanced synthesis of fibrillin-1 was blocked by rapamycin, an inhibitor of mTOR.
      Notably, IGF-I, which signals through the same pathway, also stimulated fibrillin
      1 synthesis. Systemic administration of rapamycin to mice subjected to unilateral
      ureteral obstruction, a model of renal fibrosis and increased fibrillin-1
      synthesis, markedly reduced the number of interstitial fibroblasts and fibrillin
      1 deposition. In streptozotocin-induced diabetes, IGF-I receptor was up-regulated
      in the kidneys from decorin-null mice. However, this could not compensate for the
      decorin deficiency, resulting ultimately in decreased fibrillin-1 content. This
      study provides evidence for the involvement of decorin and the IGF-I
      receptor/mTOR/p70 S6 kinase signaling pathway in the translational regulation of
      fibrillin-1.

PMID- 17200206
TI  - Hedgehog signaling promotes medulloblastoma survival via Bc/II.
AB  - Activation of the Hedgehog (Hh) pathway has been identified in several cancers,
      including medulloblastoma, but the mechanisms by which this pathway affects tumor
      survival and growth are incompletely understood. We investigated whether Hedgehog
      might promote survival of medulloblastoma cells via up-regulation of BclII. We
      found that mRNA levels of the Hedgehog pathway effector Gli1 were significantly
      associated with BclII expression in medulloblastoma and that Gli1 and BclII are
      both present in regions of decreased apoptosis in nodular medulloblastoma.
      Transient overexpression of Gli1 and Gli2 in medulloblastoma cultures induced a
      BclII transcriptional reporter and increased BclII protein levels, whereas stable
      overexpression of Gli1 was associated with increased BclII mRNA. The Hedgehog
      antagonist cyclopamine blocked expression of the Hh pathway targets PTCH1 and
      Gli1, lowered BclII levels, and increased apoptosis in DAOY and UW228
      medulloblastoma cells. Apoptotic induction caused by cyclopamine could be rescued
      in part by enforced expression of Gli1 or BclII. Hh pathway blockade also
      sensitized medulloblastoma to the effects of the proapoptotic agent lovastatin.
      These data demonstrate that BclII is an important mediator of Hh activity in
      medulloblastoma and suggest new strategies for combined chemotherapeutic
      regimens.

PMID- 17200205
TI  - Tumor cell transendothelial passage in the absorbing lymphatic vessel of
      transgenic adenocarcinoma mouse prostate.
AB  - The distribution and fine structure of the tumor-associated absorbing lymphatic
      vessel in the tumor mass of prostate adenocarcinoma and of seminal vesicle
      metastasis in transgenic mice was studied for the purpose of understanding the
      modality of tumor cell transendothelial passage from the extravasal matrix into
      the lymphatic vessel. In the tumor mass, two main cell populations were
      identified: stromal tumor cells and the invasive phenotype tumor (IPT) cells,
      having characteristics such as a highly electron-dense matrix rich in small
      granules lacking a dense core and massed nuclear chromatin, which is positive to
      immunostaining with anti-SV40 large T antigen antibody. Based on the
      ultrastructural pictures of different moments of the IPT cell transendothelial
      passage by ultrathin serial sections of the tumor-associated absorbing lymphatic
      vessel, the manner of its transendothelial passage through the intraendothelial
      channel, without involving intercellular contacts, was demonstrated. The presence
      of IPT cells in the parenchyma of satellite lymph node highlights its significant
      role in metastatic diffusion. The intraendothelial channel is the reply to the
      lack of knowledge regarding the intravasation of the tumor cell into the
      lymphatic circulation. The lymphatic endothelium would organize this channel on
      the basis of tumor cell-endothelial cell-extravasal matrix molecular
      interactions, which are as yet unidentified.

PMID- 17200207
TI  - Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive
      and noninvasive pituitary adenomas and increases invasion in human pituitary
      adenoma cell line.
AB  - The complete resection of pituitary adenomas (PAs) is unlikely when there is an
      extensive local dural invasion and given that the molecular mechanisms remain
      primarily unknown. DNA microarray analysis was performed to identify
      differentially expressed genes between nonfunctioning invasive and noninvasive
      PAs. Gene clustering revealed a robust eightfold increase in matrix
      metalloproteinase (MMP)-9 expression in surgically resected human invasive PAs
      and in the (nonfunctioning) HP75 human pituitary tumor-derived cell line treated
      with phorbol-12-myristate-13-acetate; these results were confirmed by real-time
      polymerase chain reaction, gelatin zymography, reverse transcriptase-polymerase
      chain reaction, Western blot, immunohistochemistry, and Northern blot analyses.
      The activation of protein kinase C (PKC) increased both MMP-9 activity and
      expression, which were blocked by some PKC inhibitors (Go6976,
      bisindolylmaleimide, and Rottlerin), PKC-alpha, and PKC-delta small interfering
      (si)RNAs but not by hispidin (PKC-beta inhibitor). In a transmembrane invasion
      assay, phorbol-12-myristate-13-acetate (100 nmol/L) increased the number of
      invaded HP75 cells, a process that was attenuated by PKC inhibitors, MMP-9
      antibody, PKC-alpha siRNA, or PKC-delta siRNA. These results demonstrate that MMP
      9 and PKC-alpha or PKC-delta may provide putative therapeutic targets for the
      control of PA dural invasion.

PMID- 17200208
TI  - SRC-family kinases are activated in non-small cell lung cancer and promote the
      survival of epidermal growth factor receptor-dependent cell lines.
AB  - The role of Src-family kinases (SFKs) in non-small cell lung cancer (NSCLC) has
      not been fully defined. Here we addressed this question by examining SFK
      phosphorylation in NSCLC biopsy samples and using genetic and pharmacological
      approaches to inhibit SFK expression and activity in cultured NSCLC cells.
      Immunohistochemical analysis of NSCLC biopsy samples using a Tyr416
      phosphorylation-specific, pan-SFK antibody revealed staining in 123 (33%) of 370
      tumors. Because c-Src is known to be both an upstream activator and downstream
      mediator of epidermal growth factor receptor (EGFR), we next investigated SFK
      phosphorylation in a panel of NSCLC cell lines, including ones that depend on
      EGFR for survival. The EGFR-dependent NSCLC cell lines HCC827 and H3255 had
      increased phosphorylation of SFKs, and treatment of these cells with an SFK
      inhibitor (PP1 or SKI-606) induced apoptosis. PP1 decreased phosphorylation of
      EGFR, ErbB2, and ErbB3 and strikingly enhanced apoptosis by gefitinib, an EGFR
      inhibitor. HCC827 cells transfected with c-Src short hairpin RNA exhibited
      diminished phosphorylation of EGFR and ErbB2 and decreased sensitivity to
      apoptosis by PP1 or gefitinib. We conclude that SFKs are activated in NSCLC
      biopsy samples, promote the survival of EGFR-dependent NSCLC cells, and should be
      investigated as therapeutic targets in NSCLC patients.

PMID- 17200209
TI  - Aneuploidy arises at early stages of Apc-driven intestinal tumorigenesis and
      pinpoints conserved chromosomal loci of allelic imbalance between mouse and
      human.
AB  - Although chromosomal instability characterizes the majority of human colorectal
      cancers, the contribution of genes such as adenomatous polyposis coli (APC),
      KRAS, and p53 to this form of genetic instability is still under debate. Here, we
      have assessed chromosomal imbalances in tumors from mouse models of intestinal
      cancer, namely Apc(+/1638N), Apc(+/1638N)/KRAS(V12G), and Apc(+/1638N)/Tp53-/-,
      by array comparative genomic hybridization. All intestinal adenomas from
      Apc(+/1638N) mice displayed chromosomal alterations, thus confirming the presence
      of a chromosomal instability defect at early stages of the adenoma-carcinoma
      sequence. Moreover, loss of the Tp53 tumor suppressor gene, but not KRAS
      oncogenic activation, results in an increase of gains and losses of whole
      chromosomes in the Apc-mutant genetic background. Comparative analysis of the
      overall genomic alterations found in mouse intestinal tumors allowed us to
      identify a subset of loci syntenic with human chromosomal regions (eg, 1p34-p36,
      12q24, 9q34, and 22q) frequently gained or lost in familial adenomas and sporadic
      colorectal cancers. The latter indicate that, during intestinal tumor
      development, the genetic mechanisms and the underlying functional defects are
      conserved across species. Hence, our array comparative genomic hybridization
      analysis of Apc-mutant intestinal tumors allows the definition of minimal
      aneuploidy regions conserved between mouse and human and likely to encompass rate
      limiting genes for intestinal tumor initiation and progression.

PMID- 17200210
TI  - Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging.
AB  - Vascular aging is associated with dysregulation of tumor necrosis factor (TNF)
      alpha expression. TNF-alpha is a master regulator of vascular proatherogenic
      phenotypic changes, and it has been linked to endothelial dysfunction and
      apoptosis. To test the hypothesis that anti-TNF-alpha treatment exerts
      vasculoprotective effects in aging, aged (29 months old) F344 rats were treated
      with etanercept (1 mg/kg/week for 4 weeks), which binds and inactivates TNF
      alpha. In aged carotid arteries, relaxations to acetylcholine were decreased, and
      endothelial O2* production was increased (as shown by dihydroethidine
      fluorescence measurements). Etanercept treatment significantly improved responses
      to acetylcholine and decreased vascular NAD(P)H oxidase activity and expression.
      In aged carotid and coronary arteries, there were increases in DNA fragmentation
      rate and caspase 3/7 activity (indicating an increased rate of apoptotic cell
      death), which were attenuated by etanercept treatment. In aged vessels, there was
      an up-regulation of inflammatory markers, including inducible nitric-oxide
      synthase and intercellular adhesion molecule-1, which was decreased by etanercept
      treatment. In carotid arteries of young animals, recombinant TNF-alpha elicited
      endothelial dysfunction, oxidative stress, and increased apoptosis and
      proinflammatory gene expression, mimicking many of the symptoms of vascular
      aging. Thus, we propose that anti-TNF-alpha treatment exerts anti-aging
      vasculoprotective effects.

PMID- 17200211
TI  - Overexpression of Notch1 ectodomain in myeloid cells induces vascular
      malformations through a paracrine pathway.
AB  - We previously reported that truncation of Notch1 (N1) by provirus insertion leads
      to overexpression of both the intracellular (N1(IC)) and the extracellular
      (N1(EC)) domains. We produced transgenic (Tg) mice expressing N1(EC) in T cells
      and in cells of the myeloid lineage under the regulation of the CD4 gene. These
      CD4C/N1(EC) Tg mice developed vascular disease, predominantly in the liver:
      superficial distorted vessels, cavernae, lower branching of parenchymal vessels,
      capillarized sinusoids, and aberrant smooth muscle/endothelial cell topography.
      The disease developed in lethally irradiated normal mice transplanted with Tg
      bone marrow or fetal liver cells as well as in Rag-/- Tg mice. In nude mice
      transplanted with fetal liver cells from (ROSA26 x CD4C/N1(EC)) F1 Tg mice,
      abnormal vessels were of recipient origin. Transplantation of Tg peritoneal
      macrophages into normal recipients also induced abnormal vessels. These Tg
      macrophages showed impaired functions, and their conditioned medium inhibited the
      proliferation of liver sinusoid endothelial cells in vitro. The Egr-1 gene and
      some of its targets (Jag1, FIII, FXIII-A, MCP-1, and MCP-5), previously
      implicated in hemangioma or vascular malformations, were overexpressed in Tg
      macrophages. These results show that myeloid cells can be reprogrammed by N1(EC)
      to induce vascular malformations through a paracrine pathway.

PMID- 17200212
TI  - Complement C1q reduces early atherosclerosis in low-density lipoprotein receptor
      deficient mice.
AB  - We explored the role of the classic complement pathway in atherogenesis by
      intercrossing C1q-deficient mice (C1qa-/-) with low-density lipoprotein receptor
      knockout mice (Ldlr-/-). Mice were fed a normal rodent diet until 22 weeks of
      age. Aortic root lesions were threefold larger in C1qa-/-/Ldlr-/- mice compared
      with Ldlr-/- mice (3.72 +/- 1.0% aortic root versus 1.1 +/- 0.4%; mean +/- SEM, P
      < 0.001). Furthermore, the cellular composition of lesions in C1qa-/-/Ldlr-/- was
      more complex, with an increase in vascular smooth muscle cells. The greater
      aortic root lesion size in C1qa-/-/Ldlr-/- mice occurred despite a significant
      reduction in C5b-9 deposition per lesion unit area, suggesting the critical
      importance of proximal pathway activity. Apoptotic cells were readily detectable
      by cleaved caspase-3 staining, terminal deoxynucleotidyl transferase dUTP nick
      end labeling assay, and electron microscopy in C1qa-/-/Ldlr-/-, whereas apoptotic
      cells were not detected in Ldlr-/- mice. This is the first direct demonstration
      of a role for the classic complement pathway in atherogenesis. The greater lesion
      size in C1qa-/-/Ldlr-/- mice is consistent with the emerging homeostatic role for
      C1q in the disposal of dying cells. This study suggests the importance of
      effective apoptotic cell removal for containing the size and complexity of early
      lesions in atherosclerosis.

PMID- 17200213
TI  - Summaries for patients. The effect of folic acid on hearing in older adults.

PMID- 17200214
TI  - Summaries for patients. Alcohol consumption and risk for coronary heart disease
      among men with hypertension.

PMID- 17200215
TI  - In the clinic. Type 2 diabetes.
AB  - It is nearly impossible to be a practicing internist in the United States and
      have a day of clinical work pass without encountering at least 1 patient with
      type 2 diabetes. Currently, over 20 million Americans and over 150 million
      worldwide have type 2 diabetes. Models estimate that this number will nearly
      double by the year 2050 so that about one third of adult Americans will have the
      disease. This In the Clinic feature includes answers to these and other
      practical, clinical questions... What are the diagnostic criteria for type 2
      diabetes in nonpregnant adults? Should we screen for type 2 diabetes? Can we
      prevent type 2 diabetes? What should the initial evaluation of patients with
      newly diagnosed type 2 diabetes include? What measures do U.S. stakeholders use
      to evaluate the quality of care for patients with type 2 diabetes? Only ACP
      members and individual subscribers can access the electronic features of In the
      Clinic. Non-subscribers who wish to access this issue of In the Clinic can elect
      "Pay for View." Subscribers can receive 1.5 category 1 CME credits by completing
      the CME quiz that accompanies this issue of In the Clinic. The content of In the
      Clinic is drawn from the clinical information and education resources of the
      American College of Physicians (ACP), including PIER (Physicians' Information and
      Education Resource) and MKSAP (Medical Knowledge and Self Assessment Program).
      Annals of Internal Medicine editors develop In the Clinic from these primary
      sources in collaboration with the ACP's Medical Education and Publishing division
      and with assistance of science writers and physician writers. Editorial
      consultants from PIER and MKSAP provide expert review of the content. Readers who
      are interested in these primary resources for more detail can consult
      www.acponline.org, http://pier.acponline.org, and other resources referenced
      within each issue of In the Clinic.

PMID- 17200216
TI  - Effects of folic acid supplementation on hearing in older adults: a randomized,
      controlled trial.
AB  - BACKGROUND: Age-related hearing loss is a common chronic condition of elderly
      persons. Low folate status has been associated with poor hearing. OBJECTIVE: To
      determine whether folic acid supplementation slows age-related hearing loss.
      DESIGN: Double-blind, randomized, placebo-controlled trial conducted from
      September 2000 to December 2004. SETTING: The Netherlands. PARTICIPANTS: 728
      older men and women recruited from municipal and blood bank registries with
      plasma total homocysteine concentrations 13 micromol/L or greater serum and
      vitamin B12 concentrations 200 pmol/L or greater at screening, and no middle ear
      dysfunction, unilateral hearing loss, or pathologic ear conditions unrelated to
      aging. INTERVENTION: Daily oral folic acid (800 microg) or placebo
      supplementation for 3 years. MEASUREMENTS: 3-year change in hearing thresholds,
      assessed as the average of the pure-tone air conduction thresholds of both ears
      of the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz)
      frequencies. RESULTS: Initial median hearing thresholds were 11.7 dB
      (interquartile range, 7.5 to 17.5 dB) for low frequencies and 34.2 dB
      (interquartile range, 22.5 to 50.0 dB) for high frequencies. Sixteen participants
      (2%) were lost to follow-up. After 3 years, thresholds of the low frequencies
      increased by 1.0 dB (95% CI, 0.6 to 1.4 dB) in the folic acid group and by 1.7 dB
      (CI, 1.3 to 2.1 dB) in the placebo group (difference, -0.7 dB [CI, -1.2 to -0.1
      dB]; P = 0.020). Folic acid supplementation did not affect the decline in hearing
      high frequencies. LIMITATIONS: The strict criterion for participation on the
      basis of serum homocysteine concentrations limits extrapolation to the general
      population. Folic acid fortification of food was prohibited in the Netherlands
      during the study, so baseline folate levels in participants were about half of
      those found in the U.S. population. CONCLUSIONS: Folic acid supplementation
      slowed the decline in hearing of the speech frequencies associated with aging in
      a population from a country without folic acid fortification of food. The effect
      requires confirmation, especially in populations from countries with folic acid
      fortification programs. Clinicaltrials.gov identifier: NCT00110604.

PMID- 17200217
TI  - Alcohol consumption and risk for coronary heart disease among men with
      hypertension.
AB  - BACKGROUND: Heavy alcohol consumption increases risk for hypertension, which is
      in itself a strong risk factor for cardiovascular disease (CVD). However, data on
      the association between alcohol consumption and CVD among individuals with
      hypertension are scarce. OBJECTIVE: To assess whether alcohol consumption is
      inversely associated with CVD among men with hypertension. DESIGN: Prospective
      cohort study. SETTING: United States. PARTICIPANTS: 11,711 men with hypertension
      from the Health Professionals Follow-Up Study. MEASUREMENTS: Alcohol consumption
      was assessed every 4 years by using a food-frequency questionnaire. Incident
      cases of nonfatal myocardial infarction (MI), fatal coronary heart disease, and
      stroke were documented from 1986 to 2002. RESULTS: During follow-up, 653 patients
      with MI were documented. Compared with patients abstaining from alcohol, the
      hazard ratio for participants with MI consuming 0.1 to 4.9 grams of alcohol per
      day was 1.09 (95% CI, 0.86 to 1.37); consuming 5 to 9.9 grams of alcohol per day
      was 0.81 (CI, 0.60 to 1.08 g/d); consuming 10 to 14.9 grams of alcohol per day
      was 0.68 (CI, 0.51 to 0.91 g/d); consuming 15 to 29.9 grams of alcohol per day
      was 0.72 (CI, 0.54 to 0.97 g/d); consuming 30 to 49.9 grams of alcohol per day
      was 0.67 (CI, 0.48 to 0.94 g/d); and consuming 50 or more grams of alcohol per
      day was 0.41 (CI, 0.22 to 0.77 g/d) (P < 0.001 for trend). Associations were
      similar for fatal and nonfatal MI. Alcohol consumption was not associated with
      total death or death due to CVD. Risks for total and ischemic stroke for patients
      consuming 10 to 29.9 g of alcohol per day were 1.40 (CI, 0.93 to 2.12) and 1.55
      (CI, 0.90 to 2.68) compared with that of abstainers. When corrected for
      measurement error in alcohol consumption, dietary variables, and body mass index,
      the hazard ratio for participants with MI per 12.5 grams per day increment of
      alcohol intake was 0.68 (CI, 0.46 to 1.00). LIMITATIONS: Hypertension, alcohol
      consumption, and CVD risk factors were assessed by self-report. Available data
      used to correct for measurement error were primarily restricted to dietary
      variables. CONCLUSIONS: In this population of men with hypertension, moderate
      alcohol consumption was associated with a decreased risk for MI but not with
      risks for total death or death due to CVD. As in the general population, men with
      hypertension who drink moderately and safely may not need to change their
      drinking habits.

PMID- 17200218
TI  - Susceptibility to measles, mumps, and rubella in newly arrived adult immigrants
      and refugees.
AB  - BACKGROUND: Despite effective vaccination programs for measles, mumps, and
      rubella in the United States and Canada, outbreaks continue to occur in
      susceptible subgroups, such as foreign-born persons. OBJECTIVE: To determine the
      susceptibility of newly arrived immigrants and refugees to measles, mumps, and
      rubella. DESIGN: Seroprevalence study. SETTING: Two hospitals and three community
      clinics in Montreal, Quebec, Canada. PATIENTS: 1480 adult immigrants and refugees
      who were recruited from October 2002 to December 2004. MEASUREMENTS:
      Sociodemographic and clinical data and serology for measles, mumps, and rubella.
      RESULTS: Thirty-six percent (range, 22% to 54%) of the study population was
      nonimmune to at least 1 of the 3 diseases. This proportion varied by age, sex,
      and region of origin. In multivariate analysis and after adjustment for region of
      origin, age, and socioeconomic factors, immigrant women had higher odds (odds
      ratio, 2.1) of being immune to measles (95% CI, 1.2 to 3.8) and an odds ratio of
      1.7 of being nonimmune to rubella (CI, 1.2 to 2.6) compared with immigrant men.
      LIMITATIONS: The results from the community-based convenience sample of
      immigrants may not be generalizable to all immigrant populations. CONCLUSIONS:
      Many new immigrants and refugees, particularly women, are susceptible to measles,
      mumps, or rubella and may benefit from targeted vaccination programs.

PMID- 17200219
TI  - Systematic review: efficacy and safety of rituximab for adults with idiopathic
      thrombocytopenic purpura.
AB  - BACKGROUND: Rituximab, a monoclonal anti-CD20 antibody, is increasingly used to
      treat idiopathic thrombocytopenic purpura (ITP). PURPOSE: To systematically
      review the literature on the efficacy and safety of rituximab for the treatment
      of adults with ITP. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Library,
      abstracts from the American Societies of Hematology and Clinical Oncology annual
      meetings, and bibliographies of relevant articles and reviews were searched in
      duplicate until April 2006. STUDY SELECTION: Descriptive and comparative studies
      in any language that met predefined inclusion criteria were eligible. Efficacy
      analysis was restricted to studies enrolling 5 or more patients. DATA EXTRACTION:
      Platelet count response, toxicities, dose, previous treatments, baseline platelet
      count, duration of ITP, study design, and sources of funding were extracted in
      duplicate. DATA SYNTHESIS: We identified 19 eligible reports on efficacy (313
      patients) and 29 on safety (306 patients). Weighted means for complete response
      (platelet count > 150 x 10(9) cells/L) and overall response (platelet count > 50
      x 10(9) cells/L) with rituximab were 43.6% (95% CI, 29.5% to 57.7%) and 62.5%
      (CI, 52.6% to 72.5%), respectively. Responses lasted from 2 to 48 months. Nearly
      all patients had received corticosteroids, and 53.8% had undergone splenectomy.
      Nine patients (2.9%) died. LIMITATIONS: There were no controlled studies, and no
      studies met all criteria for study quality. Reported deaths could not necessarily
      be attributed to rituximab. Overall, the number of rituximab-treated patients
      with ITP reported in the literature is small. CONCLUSIONS: Rituximab resulted in
      an overall platelet count response in 62.5% of adults with ITP. However, this
      finding derives from uncontrolled studies that also reported significant
      toxicities, including death in 2.9% of cases. These data suggest that providers
      should avoid indiscriminate use of rituximab and that randomized, controlled
      trials of rituximab for ITP are urgently needed.

PMID- 17200220
TI  - Narrative review: reversible cerebral vasoconstriction syndromes.
AB  - Reversible cerebral vasoconstriction syndromes (RCVS) comprise a group of diverse
      conditions, all characterized by reversible multifocal narrowing of the cerebral
      arteries heralded by sudden (thunderclap), severe headaches with or without
      associated neurologic deficits. Reversible cerebral vasoconstriction syndromes
      are clinically important because they affect young persons and can be complicated
      by ischemic or hemorrhagic strokes. The differential diagnosis of RCVS includes
      conditions associated with thunderclap headache and conditions that cause
      irreversible or progressive cerebral artery narrowing, such as intracranial
      atherosclerosis and cerebral vasculitis. Misdiagnosis as primary cerebral
      vasculitis and aneurysmal subarachnoid hemorrhage is common because of
      overlapping clinical and angiographic features. However, unlike these more
      ominous conditions, RCVS is usually self-limited: Resolution of headaches and
      vasoconstriction occurs over a period of days to weeks. In this review, we
      describe our current understanding of RCVS; summarize its key clinical,
      laboratory, and imaging features; and discuss strategies for diagnostic
      evaluation and treatment.

PMID- 17200221
TI  - Impact of race on the professional lives of physicians of African descent.
AB  - BACKGROUND: Increasing the racial and ethnic diversity of the physician workforce
      is a national priority. However, insight into the professional experiences of
      minority physicians is limited. This knowledge is fundamental to developing
      effective strategies to recruit, retain, and support a diverse physician
      workforce. OBJECTIVE: To characterize how physicians of African descent
      experience race in the workplace. DESIGN: Qualitative study based on in-person
      and in-depth racially concordant interviews using a standard discussion guide.
      SETTING: The 6 New England states in the United States. PARTICIPANTS: 25
      practicing physicians of African descent representing a diverse range of primary
      practice settings, specialties, and ages. MEASUREMENTS: Professional experiences
      of physicians of African descent. RESULTS: 1) Awareness of race permeates the
      experience of physicians of African descent in the health care workplace; 2) race
      related experiences shape interpersonal interactions and define the institutional
      climate; 3) responses to perceived racism at work vary along a spectrum from
      minimization to confrontation; 4) the health care workplace is often silent on
      issues of race; and 5) collective race-related experiences can result in "racial
      fatigue," with personal and professional consequences for physicians.
      LIMITATIONS: The study was restricted to New England and may not reflect the
      experiences of physicians in other geographic regions. The findings are meant to
      be hypothesis-generating and require additional follow-up studies. CONCLUSIONS:
      The issue of race remains a pervasive influence in the work lives of physicians
      of African descent. Without sufficient attention to the specific ways in which
      race shapes physicians' work experiences, health care organizations are unlikely
      to create environments that successfully foster and sustain a diverse physician
      workforce.

PMID- 17200222
TI  - BiDil for heart failure in black patients: implications of the U.S. Food and Drug
      Administration approval.
AB  - In 2005, the combination of hydralazine hydrochloride and isosorbide dinitrate
      was approved by the U.S. Food and Drug Administration (FDA) for treating heart
      failure in black patients. In departing from its long history of approving drugs
      for general clinical indications without regard to demographic classification,
      the FDA cited the need to address racial disparities in health as an important
      contributor to their decision. The authors argue that this decision, although
      perhaps well-intentioned, was based on flawed scientific interpretation of trial
      results that claimed differential drug response by race and ignored the
      considerable literature on the cause of racial disparities in health and health
      care. Because of its potential impact on future drug approvals, the FDA's
      decision is a setback in the scientific and policy discourse on medical
      therapeutics and race and specifically hinders the efforts aimed at eliminating
      health and health care disparities.

PMID- 17200223
TI  - BiDil for heart failure in black patients: The U.S. Food and Drug Administration
      perspective.
AB  - Critics of the U.S. Food and Drug Administration (FDA) approval of the fixed
      combination of hydralazine hydrochloride, 37.5 mg, and isosorbide dinitrate, 20
      mg, for treating heart failure in black patients have suggested that data were
      insufficient to distinguish treatment effects in black and white people; that
      distinctions based on race, rather than pathophysiology, were scientifically
      unreasonable; and that a "race-based" approval could be a commercial ploy to
      avoid a more expensive and prolonged full evaluation of a drug. The criticisms
      acknowledge that data supporting the approval came from a well-designed clinical
      trial in which self-identified black patients with heart failure who took
      hydralazine hydrochloride-isosorbide dinitrate with standard therapy experienced
      a statistically significant 43% (95% CI, 11% to 63%) reduction in mortality
      compared with those who took only the standard therapy. The criticisms do not
      always recognize that the decision to conduct the trial in only black patients
      reflected careful analyses of 2 previous trials in racially mixed patient
      populations that compared hydralazine hydrochloride-isosorbide dinitrate with
      placebo or with enalapril. Both trials showed little or no overall effect of
      hydralazine hydrochloride-isosorbide dinitrate in the mostly white patient
      population but hinted at a substantial effect in subsets of black patients.
      Perhaps most critically, the criticisms do not appreciate the urgency of strong
      scientific evidence of a substantial survival benefit in black patients. A
      serious attempt to avoid race-based approval by mandating study of a mixed
      population to identify a possible white patient-responder subset, particularly
      without a plausible hypothesis as to what that subset might be, would have
      required years of work, many thousands of patients, and wholly unreasonable delay
      in approval of a treatment whose effectiveness had been well-documented in the
      group for which it was intended.

PMID- 17200224
TI  - Folate supplementation and age-related hearing loss.

PMID- 17200225
TI  - Is it necessary to correct for measurement error in nutritional epidemiology?

PMID- 17200226
TI  - Black physicians' experience with race: should we be surprised?

PMID- 17200228
TI  - Defining "community" in emergency preparedness.

PMID- 17200229
TI  - Effects of a Mediterranean-style diet on cardiovascular risk factors.

PMID- 17200230
TI  - Estimated glomerular filtration rate.

PMID- 17200231
TI  - Successful thalidomide treatment of persistent chylous pleural effusion in
      disseminated lymphangiomatosis [corrected].

PMID- 17200234
TI  - T-cell-based diagnosis of neonatal multidrug-resistant latent tuberculosis
      infection.
AB  - Young children exposed to tuberculosis have a high risk of progression to severe
      tuberculosis disease, but diagnosis of recent infection is hindered by the poor
      sensitivity of the tuberculin skin test. Whether new blood tests can detect
      latent infection in this vulnerable group is unknown because there is no gold
      standard. We monitored a tuberculin skin test-negative infant whose mother had
      infectious multidrug-resistant tuberculosis with enzyme-linked immunospot, a
      blood test that enumerates Mycobacterium tuberculosis-specific T cells. The
      enzyme-linked immunospot test became persistently positive by 6 months, and 18
      months later the child developed active tuberculosis despite appropriate
      chemoprophylaxis. At this point, the magnitude of the enzyme-linked immunospot
      response increased >10-fold. Our findings demonstrate that this blood test
      detected latent infection with dormant, yet viable, bacilli and illustrate how
      enzyme-linked immunospot could improve diagnosis of childhood tuberculosis
      infection.

PMID- 17200233
TI  - Highly efficient concerted evolution in the ribosomal DNA repeats: total rDNA
      repeat variation revealed by whole-genome shotgun sequence data.
AB  - Repeat families within genomes are often maintained with similar sequences.
      Traditionally, this has been explained by concerted evolution, where repeats in
      an array evolve "in concert" with the same sequence via continual turnover of
      repeats by recombination. Another form of evolution, birth-and-death evolution,
      can also explain this pattern, although in this case selection is the critical
      force maintaining the repeats. The level of intragenomic variation is the key
      difference between these two forms of evolution. The prohibitive size and
      repetitive nature of large repeat arrays have made determination of the absolute
      level of intragenomic repeat variability difficult, thus there is little evidence
      to support concerted evolution over birth-and-death evolution for many large
      repeat arrays. Here we use whole-genome shotgun sequence data from the genome
      projects of five fungal species to reveal absolute levels of sequence variation
      within the ribosomal RNA gene repeats (rDNA). The level of sequence variation is
      remarkably low. Furthermore, the polymorphisms that are detected are not
      functionally constrained and seem to exist beneath the level of selection. These
      results suggest the rDNA is evolving via concerted evolution. Comparisons with a
      repeat array undergoing birth-and-death evolution provide a clear contrast in the
      level of repeat array variation between these two forms of evolution, confirming
      that the rDNA indeed does evolve via concerted evolution. These low levels of
      intra-genomic variation are consistent with a model of concerted evolution in
      which homogenization is very rapid and efficiently maintains highly similar
      repeat arrays.

PMID- 17200232
TI  - Serum response factor binding sites differ in three human cell types.
AB  - The serum response factor (SRF) is essential for embryonic development and
      maintenance of muscle cells and neurons. The mechanism by which this factor
      controls these divergent pathways is unclear. Here we present a genome-wide view
      of occupancy of SRF at its binding sites with a focus on those that vary with
      cell type. We used chromatin immunoprecipitation (ChIP) in combination with human
      promoter microarrays to identify 216 putative SRF binding sites in the human
      genome. We performed independent quantitative PCR validation at over half of
      these sites that resulted in 146 sites we assert to be true binding sites at over
      90% confidence. Nearly half of the sites are bound by SRF in only one of the
      three cell types we tested, providing strong evidence for the diverse roles for
      SRF in different cell types. We also explore possible mechanisms controlling
      differential binding of SRF in these cell types by assaying cofactor binding, DNA
      methylation, histone methylation, and histone acetylation at a subset of sites
      bound preferentially in smooth muscle cells. Although we did not see a strong
      correlation between SRF binding and epigenetics modifications, at these sites, we
      propose that SRF cofactors may play an important role in determining cell
      dependent SRF binding sites. ELK4 (previously known as SAP-1 [SRF-associated
      protein-1]) is ubiquitously expressed. Therefore, we expected it to occupy sites
      where SRF binding is common in all cell types. Indeed, 90% of SRF sites also
      bound by ELK4 were common to all three cell types. Together, our data provide a
      more complete understanding of the regulatory network controlled by SRF.

PMID- 17200236
TI  - Pediatrician characteristics associated with attention to spirituality and
      religion in clinical practice.
AB  - OBJECTIVE: The literature suggests that a majority of pediatricians believe that
      spirituality and religion are relevant in clinical practice, but only a minority
      gives them attention. This project explored this disparity by relating
      personal/professional characteristics of pediatricians to the frequency with
      which they give attention to spirituality and religion. METHODS: Pediatricians (N
      = 737) associated with 3 academic Midwestern pediatric hospitals responded to a
      survey that requested information concerning the frequency with which they (1)
      talked with patients/families about their spiritual and religious concerns and
      (2) participated with them in spiritual or religious practices (eg, prayer). The
      associations between these data and 10 personal and professional characteristics
      were examined. RESULTS: The results demonstrated the disparity, and the analysis
      identified 9 pediatrician characteristics that were significantly associated with
      more frequently talking with patients/families about their spiritual and
      religious concerns. The characteristics included increased age; a Christian
      religious heritage; self-description as religious; self-description as spiritual;
      the importance of one's own spirituality and religion in clinical practice; the
      belief that the spirituality and religion of patients/families are relevant in
      clinical practice; formal instruction concerning the role of spirituality and
      religion in health care; relative comfort asking about beliefs; and relative
      comfort asking about practices. All of these characteristics except pediatrician
      age were also significantly associated with the increased frequency of
      participation in spiritual and religious practices with patients/families.
      CONCLUSIONS: Attention to spiritual and religious concerns and practices are
      associated with a web of personal and professional pediatrician characteristics.
      Some characteristics pertain to the physician's personal investment in
      spirituality and religion in their own lives, and others include being
      uncomfortable with spiritual and religious concerns and practices. These
      associations shed light on the disparity between acknowledged spirituality and
      religion relevancy and inattention to it in clinical practice.

PMID- 17200235
TI  - A national assessment of knowledge, attitudes, and confidence of prehospital
      providers in the assessment and management of child maltreatment.
AB  - OBJECTIVE: The goal was to assess the knowledge and confidence in recognition,
      management, documentation, and reporting of child maltreatment among a
      representative sample of emergency medical services personnel in the United
      States. METHODS: A questionnaire was developed and pilot-tested, with the input
      of experts in emergency medical services and child maltreatment, to assess
      knowledge, attitudes, confidence, and training needs regarding assessment and
      treatment of child maltreatment. The questionnaire was distributed nationally to
      a random sample of prehospital providers by using a previously validated sampling
      plan. RESULTS: Of 2863 surveys sent to prehospital providers, 1237 (43%) were
      returned. Most prehospital providers reported receiving < or = 1 hour of
      continuing medical education regarding child maltreatment. Most (78%) asked for
      additional educational opportunities, with only 3% stating that they required no
      additional training. Participants lacked knowledge regarding the developmental
      abilities of children, management of families in which child maltreatment is
      suspected, key elements of the history that should be noted, and the degree of
      suspicion necessary for reporting. CONCLUSIONS: Prehospital providers expressed
      confidence in their abilities to recognize and to manage cases of child abuse and
      neglect; however, significant deficiencies were reported in several critical
      knowledge areas, including identification of child maltreatment, interviewing
      techniques, and appropriate documentation.

PMID- 17200237
TI  - Cost-effectiveness of routine childhood vaccination for hepatitis A in the United
      States.
AB  - OBJECTIVES: Economic analysis is an important component in formulating national
      policy. We evaluated the economic impact of hepatitis A vaccination of all US
      children ages 12 to 23 months as compared with no vaccination and with current
      implementation of the preexisting (issued in 1999), regional policy. METHODS: We
      developed a Markov model of hepatitis A that followed a single cohort from birth
      in 2005 through death or age 95 years. From the societal perspective, the model
      compared the outcomes that resulted from routine vaccination at age 1 year to 2
      scenarios: no hepatitis A vaccination and hepatitis A vaccination at levels
      observed in 2003 under the preexisting policy. We evaluated the economic impact
      of vaccination nationwide, in areas where vaccination was already recommended,
      and in areas where no previous recommendation existed. RESULTS: Without childhood
      vaccination, the approximately 4 million children in the 2005 birth cohort would
      be expected over their lifetimes to have 199,000 hepatitis A virus infections,
      including 74,000 cases of acute hepatitis A and 82 deaths, resulting in 134
      million dollars in hepatitis A-related medical costs and productivity losses.
      Compared with no vaccination, routine vaccination at age 1 year would prevent
      172,000 infections, at a cost of 28,000 dollars per quality-adjusted life year
      saved. Compared with maintaining the levels of hepatitis A vaccination under the
      preexisting regional policy, routine vaccination at age 1 year would prevent an
      additional 112,000 infections, at a cost of 45,000 dollars per quality-adjusted
      life year saved. CONCLUSIONS: The cost-effectiveness of nationwide hepatitis A
      vaccination compared with no vaccination, and the incremental cost-effectiveness
      of this recommendation compared with preexisting recommendations, is similar to
      that of other accepted public health interventions. In October 2005, the Advisory
      Committee on Immunization Practices recommended extending hepatitis A
      immunization to all US children ages 12 to 23 months.

PMID- 17200238
TI  - Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus
      simethicone in the treatment of infantile colic: a prospective randomized study.
AB  - OBJECTIVE: The goal was to test the hypothesis that oral administration of
      Lactobacillus reuteri in a prospective randomized study would improve symptoms of
      infantile colic. METHODS: Ninety breastfed colicky infants were assigned randomly
      to receive either the probiotic L. reuteri (10(8) live bacteria per day) or
      simethicone (60 mg/day) each day for 28 days. The mothers avoided cow's milk in
      their diet. Parents monitored daily crying times and adverse effects by using a
      questionnaire. RESULTS: Eighty-three infants completed the trial: 41 in the
      probiotic group and 42 in the simethicone group. The infants were similar
      regarding gestational age, birth weight, gender, and crying time at baseline.
      Daily median crying times in the probiotic and simethicone groups were 159
      minutes/day and 177 minutes/day, respectively, on the seventh day and 51
      minutes/day and 145 minutes/day on the 28th day. On day 28, 39 patients (95%)
      were responders in the probiotic group and 3 patients (7%) were responders in the
      simethicone group. No adverse effects were reported. CONCLUSIONS: In our cohort,
      L. reuteri improved colicky symptoms in breastfed infants within 1 week of
      treatment, compared with simethicone, which suggests that probiotics may have a
      role in the treatment of infantile colic.

PMID- 17200239
TI  - Improvement in booster seat use in Tennessee.
AB  - OBJECTIVE: Tennessee enacted an enhanced child safety restraint law in July 2004,
      which included new requirements for booster seat use among 4- to 8-year-old
      children. The goal of this study was to evaluate the appropriate use of child
      safety restraints and knowledge of the enhanced law before and after its
      implementation. METHODS: On-site child safety restraint assessments and brief
      driver interviews for cars with passengers 0 to 8 years of age were conducted at
      34 sites in 3 urban counties in Tennessee. Assessments were conducted 2 to 3
      months before implementation of the law and 1 year after implementation of the
      law. Appropriateness of restraint use was defined on the basis of language in the
      enhanced law. RESULTS: Data were obtained for 1247 child passengers transported
      by 1191 drivers; 333 of the children were 0 to 3 years of age, and 914 were 4 to
      8 years of age (the primary age group targeted by the enhanced law). Significant
      improvement in appropriate booster seat use was seen for 4- to 8-year-old
      passengers after implementation (39%), compared with use before implementation
      (29%). There was no improvement in the rate of appropriate restraint use for
      younger children (<4 years of age) after implementation. Black passengers 4 to 8
      years of age were twice as likely as white child passengers to be unrestrained,
      before and after implementation. Seventy-nine percent of drivers reported
      awareness of the new restraint law after implementation; the majority of drivers
      obtained information from television advertisements. CONCLUSIONS: Improvements in
      booster seat use were seen after adoption of an enhanced state law requiring use;
      however, racial differences in restraint use persisted among 4- to 8-year-old
      passengers. Additional study of barriers to booster seat use among drivers of
      black child passengers and unrestrained children is warranted.

PMID- 17200240
TI  - Breastfeeding and infant eczema in the first year of life in the KOALA birth
      cohort study: a risk period-specific analysis.
AB  - OBJECTIVE: We studied the association between breastfeeding and eczema, taking
      into account the possible influence of reverse causation, with risk period
      specific analyses. METHODS: Information on breastfeeding, determinants, and
      outcomes at 1 year of age was collected with repeated questionnaires for 2405
      mother-infant pairs participating in the KOALA (Child, Parent and Health:
      Lifestyle and Genetic Constitution [in Dutch]) birth cohort study. By using
      multivariate logistic regression analysis, we compared an overall analysis with
      risk period-specific analyses. RESULTS: By the age of 1 year, 535 infants (22.2%)
      had developed eczema. In an overall analysis, we found a weak nonsignificant
      trend toward a reduced risk of eczema in the first year of life with increasing
      duration of breastfeeding (lowest risk for those breastfed for > or = 7 months
      versus never breastfed). In the risk period-specific analysis (confined to
      infants "at risk" for eczema onset after 3 months of age), no indication for
      reverse causation was found (results were not very different, compared with the
      overall analysis). Infants who were breastfed from birth on had a slightly
      (although not statistically significantly) increased risk for eczema in the first
      3 months of life, compared with infants who were formula fed from birth on.
      CONCLUSIONS: Our results indicated that no strong effect of breastfeeding on
      eczema in the first year of life was present. This conclusion was strengthened by
      risk period-specific analysis, which made the influence of reverse causation
      unlikely.

PMID- 17200241
TI  - Physician advice about being overweight: association with self-reported weight
      loss, dietary, and physical activity behaviors of US adolescents in the National
      Health and Nutrition Examination Survey, 1999-2002.
AB  - OBJECTIVE: The goal was to examine the association of physician counseling about
      being overweight with attempted weight loss, dietary, and physical
      activity/inactivity behaviors of US teens. METHODS: We used data from the
      National Health and Nutrition Examination Surveys 1999-2000 and 2001-2002 for 16-
      to 19-year-old subjects with BMI for age of > or = 85th percentile (n = 716).
      Regression methods were used to examine the association of physician advice about
      teen weight status with covariate-adjusted differences in reported weight loss,
      dietary, and physical activity behaviors. RESULTS: Approximately 51% of
      overweight teens (BMI for age of > or = 95th percentile) but only 17% of at-risk
      teens (BMI for age of 85th to < 95th percentile) reported that they had been
      informed by a doctor about being overweight. More than 60% of those told by a
      doctor about being overweight had attempted weight loss in the past year,
      relative to 41% of those who did not receive this advice. Teens informed of their
      overweight status reported significantly smaller amounts of all foods and
      beverages and lower energy intake per kilogram of body weight in the 24-hour
      recall, relative to the comparison group. Physical activity and inactivity
      behaviors were unrelated to professional counseling about overweight status.
      CONCLUSION: Physician counseling regarding adolescent overweight status was
      associated with a positive impact on attempted weight loss and moderate dietary
      behaviors.

PMID- 17200242
TI  - Identification of overweight status is associated with higher rates of screening
      for comorbidities of overweight in pediatric primary care practice.
AB  - OBJECTIVES: The goals were to determine whether primary care provider
      identification of children as overweight was associated with additional screening
      or referrals and whether the types and numbers of visits to primary care differed
      for overweight and nonoverweight children. METHODS: Sequential parents/guardians
      at 13 diverse pediatric practices completed an in-office survey addressing health
      habits and demographic features. Medical records of each child from a sample of
      families were reviewed. Data were abstracted from the first visit and from all
      visits in the 14-month period before study enrollment. Analyses were limited to
      children > or = 2 years of age for whom BMI percentile could be calculated.
      RESULTS: The analytic sample included 1216 children (mean age: 7.9 years; 51%
      male) from 777 families (parents were 43% white, 18% black, 34% Hispanic, and 5%
      other; 49% of families had a child receiving Medicaid/uninsured). Among
      overweight children (BMI of > or = 95th percentile; n = 248), 28% had been
      identified as such in the record. Screening or referral for evaluation of
      comorbidities was more likely among overweight children who were identified in
      the record (54%) than among overweight children who were not identified (17%).
      Among children at risk of overweight (BMI of 85th to 94th percentile; n = 186),
      5% had been identified as such in the record and overall 15% were
      screened/referred. In logistic regression modeling, the children identified as
      overweight/at risk of overweight had 6 times greater odds of receiving any
      management for overweight. CONCLUSIONS: Low rates of identification of overweight
      status and evaluation or referrals for comorbidities were found. Identification
      of overweight status was associated with a greatly increased rate of screening
      for comorbidities.

PMID- 17200244
TI  - Sleep arrangements and behavior of bed-sharing families in the home setting.
AB  - OBJECTIVES: We aimed to provide a quantitative analysis of the sleep arrangements
      and behaviors of bed-sharing families to further understand the risks and
      benefits as well as the effects of infant age and room temperature on bed-sharing
      behaviors. METHODS: Forty infants who regularly bed shared with > or = 1 parent >
      or = 5 hours per night were recruited. Overnight video of the family and
      physiological monitoring of the infant was conducted in infants' homes. Infant
      sleep position, potential for exposure to expired air, head covering and
      uncovering, breastfeeding, movements, family sleep arrangements, responses to the
      infant, and interactions were logged. RESULTS: All infants slept with their
      mother. Fathers were included in 18 studies and siblings in 4. Infants usually
      slept beside the mother, separated from the father/siblings (if present), facing
      the mother, with head at mothers' breast level, touching, or with mother
      cradling. Median overnight breastfeeding duration was 40.5 minutes. Mothers
      commonly faced their infant, but infants were rarely in a position that
      potentially exposed them to maternal expired air. Fathers were seldom in contact
      with the infant during sleep. Of the 102 head-covering episodes observed in 22
      infants, 80% were because of changes in adult sleep position. Sixty-eight percent
      of head uncovering was facilitated by the mother; half of these events were
      prompted by the infant. A 1 degree C increase in room temperature decreased
      infant head covering by 0.2 hours. CONCLUSIONS: The mother-infant relationship is
      of prime importance during bed sharing, whether the father is present or not. The
      focus around breastfeeding often dictates the sleep position of the infant and
      mother, though room temperature may also influence this. In colder rooms infants
      tend to spend more time with their face covered by bedding. Frequent maternal
      interactions rely on the ability of the mother to arouse with little stimulation.
      Mothers, perhaps impaired by alcohol, smoking, or overtiredness, may not be able
      to respond appropriately.

PMID- 17200243
TI  - Hopeful thinking and level of comfort regarding providing pediatric palliative
      care: a survey of hospital nurses.
AB  - OBJECTIVE: The purpose of this work was to test the hypothesis that individual
      nurses' level of hope is associated with greater self-reported comfort and
      competence in providing palliative care. METHODS: We conducted a Web-based cross
      sectional survey at the Children's Hospital of Philadelphia, a large referral
      hospital, during the spring of 2005 with all of the employed nurses. The response
      rate was 44% (410 of 932 eligible nurses). The questions were adapted from
      published studies or written for this study regarding nurses' knowledge,
      attitudes, practices, and experiences regarding various aspects of palliative
      care. We used the Adult Dispositional Hope Scale. RESULTS: Respondents, asked to
      rate their degree of agreement (+2, strongly agree to -2, strongly disagree) with
      the statement that they were "comfortable working with dying children and their
      families," reported a mean score of 0.5. Regarding whether they "find it very
      difficult to talk about death and dying with children and families," the mean
      score was -0.1. Nurses specifically reported feeling most competent regarding
      pain management and least competent regarding talking with children and families
      about dying. After multivariable adjustment, greater number of years in nursing
      practice, more hours of palliative care education, and higher scores on the Hope
      Scale, each were significantly associated with higher levels of comfort working
      with dying children and the families, lower levels of difficulty talking about
      death and dying, and higher levels of palliative care competency. CONCLUSIONS:
      Nurses' level of hope is associated with their self-reported comfort and
      competence regarding palliative care.

PMID- 17200245
TI  - Barriers to the identification and management of psychosocial issues in children
      and maternal depression.
AB  - CONTEXT: Child psychosocial issues and maternal depression are underidentified
      and undertreated, but we know surprisingly little about the barriers to
      identification and treatment of these problems by primary care pediatricians.
      OBJECTIVES: The purpose of this work was to determine whether (1) perceived
      barriers to care for children's psychosocial issues and maternal depression
      aggregate into patient, physician, and organizational domains, (2) barrier
      domains are distinct for mothers and children, and (3) physician, patient, and
      practice/organizational characteristics are associated with different barrier
      domains for children and mothers. METHODS: We conducted a cross-sectional survey
      of the 50,818 US nonretired members of the American Academy of Pediatrics. Of a
      random sample of 1600 members, 832 (745 nontrainee members) responded. This was a
      mailed 8-page survey with no patients and no intervention. We measured physician
      assessment of barriers to providing psychosocial care for children's psychosocial
      problems and maternal depression. RESULTS: Pediatricians frequently endorse the
      lack of time to treat mental health problems (77.0%) and long waiting periods to
      see mental health providers (74.0%) as the most important barriers to the
      identification and treatment of children's psychosocial problems. For maternal
      depression, pediatricians most often endorsed lack of training in treatment
      (74.5%) and lack of time to treat (64.3%) as important barriers. Pediatricians'
      reports of barriers clustered into physician and organizational domains.
      Physician domains were distinct for children and mothers, but organizational
      domains were not. Several physician and practice characteristics are
      significantly associated with the 4 barrier scales, and different characteristics
      (eg, sociodemographic, attitudinal, and practice features) were related to each
      barrier area. CONCLUSIONS: Pediatricians endorse a wide range of barriers with
      respect to the diagnosis and treatment of children's mental health problems and
      maternal depression. The specificity of factors relating to various barrier areas
      suggests that overcoming barriers to the identification and treatment of child
      mental health problems and maternal depression in primary care pediatrics is
      likely to require a multifaceted approach that spans organizational, physician,
      and patient issues. In addition, comprehensive interventions will likely require
      social marketing approaches designed to engage diverse audiences of clinicians
      and their patients to participate.

PMID- 17200246
TI  - Potential for donation after cardiac death in a children's hospital.
AB  - OBJECTIVES: A task force was convened to decide whether a donation after cardiac
      death policy should be implemented at Children's Hospital Boston. As part of this
      process, we sought to determine the number of potential kidney donation after
      cardiac death donors in our PICUs. METHODS: We examined all 254 deaths in the
      Medical/Surgical ICU and the Cardiac ICU from 2002 to 2004 and identified
      potential donation after cardiac death donors. Inclusion criteria were age > or =
      3 months, mechanical ventilation, and creatinine < or = 1.5 mg/dL. Exclusion
      criteria were HIV infection, malignancy other than primary brain tumor or
      nonmelanoma skin cancer, evidence of ongoing infection, death despite
      resuscitation attempts, and brain death. RESULTS: Twenty-one of the 254 deaths
      met criteria for brain death, and 233 patients did not. Of the 116 patients > 3
      months of age for whom life support was withdrawn, 92 were not suitable for
      kidney donation after cardiac death. Of the 24 children identified as potentially
      eligible for donation after cardiac death, 14 died within 1 hour of withdrawal of
      support and could have proceeded with donation after cardiac death. In the other
      10 children, donation would have been aborted because of prolonged time to death.
      CONCLUSIONS: Of all patients who died in our ICUs, 5.5% would have been potential
      candidates for donation after cardiac death. Assuming the rates of parental
      consent are similar to that of our heart-beating organ donors (47%), a donation
      after cardiac death protocol could have potentially yielded 7 additional organ
      donors and 14 additional kidneys over this 3-year period.

PMID- 17200247
TI  - The economics of routine childhood hepatitis A immunization in the United States:
      the impact of herd immunity.
AB  - OBJECTIVES: Because of the herd-immunity phenomenon, the benefits of immunization
      against hepatitis A extend beyond those received by those who are vaccinated.
      This analysis estimates the impact of herd immunity on the cost-effectiveness of
      routine hepatitis A immunization among US children. PATIENTS AND METHODS: In an
      economic model, the costs and benefits of hepatitis A immunization were estimated
      for immunizing all US children at age 1 year over a 10-year period starting in
      2005. The future burden of disease from hepatitis A was also estimated with this
      model, and the fraction that would be prevented by herd immunity was modeled by
      using a previously published analysis of the relationship between hepatitis A
      vaccination coverage and declines in hepatitis A incidence. RESULTS: Without
      accounting for herd-immunity effects, the costs of routine immunization would
      average 32,000 dollars per quality-adjusted life-year gained for the first 10
      cohorts immunized starting with the 2005 birth cohort. Herd-immunity effects
      would be expected to produce substantial additional benefits, lowering the cost
      of the immunization program to 1000 dollars per quality-adjusted life-year gained
      for the first 10 cohorts. Herd-immunity benefits would be greatest for the first
      few cohorts, more than doubling the benefits of immunization, and would decline
      over time. In a univariate sensitivity analysis, estimates were most sensitive to
      vaccination costs but remained below 20,000 dollars per quality-adjusted life
      year under all of the assumptions. CONCLUSIONS: Herd-immunity effects more than
      double the savings from hepatitis A immunization during the first 10 years of the
      program. After accounting for these effects, immunization is close to cost
      neutral on a cost-per-quality-adjusted-life-year basis.

PMID- 17200248
TI  - Early life exposure to antibiotics and the subsequent development of eczema,
      wheeze, and allergic sensitization in the first 2 years of life: the KOALA Birth
      Cohort Study.
AB  - OBJECTIVES: Antibiotic exposure in early life may be associated with atopic
      disease development either by interfering with bacterial commensal flora or by
      modifying the course of bacterial infections. We evaluated early life exposure to
      antibiotics and the subsequent development of eczema, wheeze, and allergic
      sensitization in infancy. METHODS: Information on antibiotic use in the first 6
      months and eczema and wheeze until age 2 was collected by repeated questionnaires
      in 2764 families participating in the KOALA (Child, Parent and Health: Lifestyle
      and Genetic Constitution [in Dutch]) Birth Cohort Study in The Netherlands.
      Antibiotic intake was evaluated both as maternal antibiotic use during
      breastfeeding and infant oral medication. Venous blood samples taken from 815
      infants at 2 years of age were analyzed for total and specific immunoglobulin E
      against common food and inhalant allergens using a radioallergosorbent test.
      Multivariate logistic regression analysis was used to adjust for confounding
      factors. RESULTS: During the first 2 years, eczema was present in 32% of all
      infants, recurrent wheeze in 11%, and prolonged wheezing in 5%. At 2 years old,
      27% of children were sensitized against > or = 1 allergen. At 6 months old, 11%
      had been exposed to antibiotics through breast milk and 20% directly through
      medication. The risk for recurrent wheeze, and prolonged wheeze was higher in
      infants directly exposed to antibiotics through medication, also after excluding
      from the analyses children who wheezed in the same period as an antibiotic had
      been used (avoiding reverse causation). Antibiotic use through breastfeeding was
      associated with recurrent wheeze, but prolonged wheeze was not. Eczema and
      sensitization were not associated with antibiotic exposure. CONCLUSIONS: We
      demonstrated that early antibiotic use preceded the manifestation of wheeze but
      not eczema or allergic sensitization during the first 2 years of life. Different
      biological mechanisms may underlie the etiology of wheeze compared with eczema or
      sensitization. Antibiotic exposure through breastfeeding enhanced the risk for
      recurrent wheeze, but this needs further confirmation.

PMID- 17200249
TI  - XXY (Klinefelter syndrome): a pediatric quantitative brain magnetic resonance
      imaging case-control study.
AB  - OBJECTIVE: An extra X chromosome in males (XXY), known as Klinefelter syndrome,
      is associated with characteristic physical, cognitive, and behavioral features of
      variable severity. The objective of this study was to examine possible
      neuroanatomical substrates of these cognitive and behavioral features during
      childhood and adolescence. METHODS: MRI brain scans were acquired for 42 XXY and
      87 healthy XY age-matched control males. We compared these 2 groups on regional
      brain volumes and cortical thickness. RESULTS: Total cerebral volume and all
      lobar volumes except parietal white matter were significantly smaller in the XXY
      group, whereas lateral-ventricle volume was larger. Consistent with the cognitive
      profile, the cortex was significantly thinner in the XXY group in left inferior
      frontal, temporal, and superior motor regions. CONCLUSION: The brain-imaging
      findings of preferentially affected frontal, temporal, and motor regions and
      relative sparing of parietal regions are consistent with observed cognitive and
      behavioral strengths and weaknesses in XXY subjects.

PMID- 17200250
TI  - SunSafe in the Middle School Years: a community-wide intervention to change early
      adolescent sun protection.
AB  - OBJECTIVE: Rising rates of skin cancer associated with early-life sun exposure
      make it important to improve adolescent sun-protection practices. Our study
      objective was to determine if a multicomponent community-wide intervention could
      alter the decline in sun protection that begins in early adolescence. METHODS: A
      randomized, controlled trial was conducted in 10 communities to assess the impact
      of the SunSafe in the Middle School Years program. The intervention sought to (1)
      educate and activate adults and peers to role model and actively promote sun
      protection practices and (2) create a pro-sun protection community environment.
      It targeted school personnel, athletic coaches, lifeguards, and clinicians and
      enlisted teens as peer advocates. Annual observations of cross-sectional samples
      of teens at community beach/pool sites were used to assess the impact of 1 and 2
      years of intervention exposure compared to grade-matched controls. The outcome
      was percent of body surface protected by sunscreen, clothing, or shade. RESULTS:
      Observers determined the sun protection level of 1927 adolescents entering 6th to
      8th grades. After 2 years of intervention exposure, adolescents at the beach/pool
      in intervention communities were significantly better protected than those in
      control communities. Over 2 years, the percent of body surface area protected
      declined by 23% in the control arm but only 8% in intervention arm. After
      intervention, the average percent of body surface protected at intervention sites
      (66.1%) was significantly greater than control sites (56.8%). Teens in
      intervention communities reported sun-protection advice from more adult sources,
      were more likely to use sunscreen, and applied it more thoroughly than control
      site teens. CONCLUSIONS: Our multicomponent model addressing adolescent sun
      protection shows the power of engaging teens and adults from across the community
      as role models and educators. This new ecological approach shows promise in
      changing adolescent sun protection behaviors and reducing skin cancer risks.

PMID- 17200251
TI  - The effect of birth in secondary- or tertiary-level hospitals in Finland on
      mortality in very preterm infants: a birth-register study.
AB  - OBJECTIVE: Our goal was to test the hypothesis that the level of the delivery
      hospital affects 1-year mortality of very preterm infants in Finland. PATIENTS
      AND METHODS: This retrospective national medical birth-register study included
      2291 very preterm infants (gestational age of < 32 weeks at birth or birth weight
      of < or = 1500 g) born in 14 level II (central) and 5 level III (university)
      hospitals in 2000-2003. The main outcome measures were adjusted total mortality
      (including stillbirths) and mortality of live-born infants until the age of 1
      year. RESULTS: Both the total 1-year mortality and the 1-year mortality of live
      born infants were higher in level II hospitals compared with level III hospitals.
      Total mortality was higher in very preterm infants who were not born during
      office hours. In theory, delivery of all very preterm infants in level III
      instead of level II hospitals translates into an annual prevention of 69 of the
      170 total deaths and prevention of 18 of the 45 deaths of live-born infants.
      CONCLUSIONS: Resources in neonatal intensive care should be increased, especially
      during non-office hours, to have an equally distributed service through the 24
      hour day. More efficient regionalization of very preterm deliveries may improve 1
      year survival of very preterm infants in Finland.

PMID- 17200252
TI  - A randomized, controlled trial of heparin versus placebo infusion to prolong the
      usability of peripherally placed percutaneous central venous catheters (PCVCs) in
      neonates: the HIP (Heparin Infusion for PCVC) study.
AB  - BACKGROUND: Mechanical and infectious complications shorten the effective
      duration of peripherally inserted central venous catheters. Heparin use to
      prevent such complications and prolong the usability of peripherally inserted
      central venous catheters is inconclusive. OBJECTIVE: Our goal was to evaluate the
      effectiveness of heparin in prolonging the usability of peripherally inserted
      central venous catheters in neonates. DESIGN/METHODS: We performed a multicenter,
      randomized, controlled trial of heparin infusion (0.5 U/kg per hour) versus
      placebo for peripherally inserted central venous catheters in neonates. The
      primary outcome was duration of catheter use. Secondary outcomes were occlusion,
      catheter-related sepsis, thrombosis, and adverse effects of heparin. To detect a
      168-hour (1-week) difference in the duration of catheter use, 192 patients were
      needed. Kaplan-Meier and Cox regression analyses were performed. RESULTS: A total
      of 201 neonates were enrolled (heparin group: n = 100; control group: n = 101).
      Baseline demographics were similar between the groups. Duration of catheter use
      was longer in the infants in the heparin versus the placebo group. Study center,
      gender, birth weight, and type and position of the catheter were not predictors
      of duration of catheter use. For those in the heparin versus the placebo group,
      the incidence of elective catheter removal (therapy completed) was 63% vs 42%, of
      occlusion was 6% vs 31%, of thrombosis was 20% vs 21%, and of catheter-related
      sepsis was 10% vs 6%, respectively. No adverse events were noted. CONCLUSIONS:
      Heparin infusion prolonged the duration of peripherally inserted central venous
      catheter usability, which permitted a higher percentage of neonates to complete
      therapy without increasing adverse effects.

PMID- 17200253
TI  - First report of autologous cord blood transplantation in the treatment of a child
      with leukemia.
AB  - We present the case of a 3-year-old girl with acute lymphoblastic leukemia who
      developed isolated central nervous system relapse while receiving chemotherapy 10
      months after diagnosis. The child achieved a second remission on retreatment with
      systemic and intrathecal chemotherapy. She then underwent myeloablative
      chemotherapy and radiation therapy followed by infusion of her own umbilical cord
      blood, which the parents had saved after her delivery. She is now doing well and
      is in complete remission 20 months after cord blood transplantation. In this
      first report of autologous cord blood transplantation for treatment of childhood
      leukemia, we discuss the safety and feasibility of this procedure as well as some
      of the uncertainties surrounding autologous cord blood collection and usage.

PMID- 17200254
TI  - Is dieting advice from magazines helpful or harmful? Five-year associations with
      weight-control behaviors and psychological outcomes in adolescents.
AB  - OBJECTIVE: The purpose of this study was to evaluate the association between
      frequent reading of magazine articles about dieting/weight loss and weight
      control behaviors and psychological outcomes 5 years later in a sample of
      adolescents. PARTICIPANTS AND METHODS: Data are from Project EAT (Eating Among
      Teens), a 5-year longitudinal study of eating, activity, weight, and related
      variables in 2516 middle and high school students. In 1999 (time 1), participants
      completed surveys and had their height and weight measured. In 2004 (time 2),
      participants were resurveyed. RESULTS: For female adolescents, the frequency of
      healthy, unhealthy, and extreme weight-control behaviors increased with
      increasing magazine reading after adjusting for time 1 weight-control behaviors,
      weight importance, BMI, and demographic covariates. The odds of engaging in
      unhealthy weight-control behaviors (such as fasting, skipping meals, and smoking
      more cigarettes) were twice as high for the most frequent readers compared with
      those who did not read magazine articles about dieting and weight loss. The odds
      of using extreme weight-control behaviors (such as vomiting or using laxatives)
      were 3 times higher in the highest frequency readers compared with those who did
      not read such magazines. There were no significant associations for either weight
      control behaviors or psychological outcomes for male adolescents. CONCLUSIONS:
      Frequent reading of magazine articles about dieting/weight loss strongly
      predicted unhealthy weight-control behaviors in adolescent girls, but not boys, 5
      years later. Findings from this study, in conjunction with findings from previous
      studies, suggest a need for interventions aimed at reducing exposure to, and the
      importance placed on, media messages regarding dieting and weight loss.

PMID- 17200255
TI  - An unusual case of severe therapy-resistant hypertension in a newborn.
AB  - Hypertension can occur in up to 2% of neonates, and the spectrum of potential
      causes is broad. Prompt and thorough evaluation with a main focus on kidney
      disease is key for appropriate therapy. Here we describe a 2-day-old neonate with
      feeding intolerance and elevated blood pressure readings. Within 24 hours after
      birth, the infant's blood pressure increased significantly, with sustained mean
      arterial pressure >85. Renal Doppler ultrasound showed decreased venous blood
      flow in the right kidney with an abnormal Doppler wave form suggestive of
      unilateral renal venous thrombosis. Despite aggressive antihypertensive therapy
      including hydralazine and enalaprilat, hypertension remained sustained. On day-of
      life 4, the infant developed clinical signs of hypertensive encephalopathy and
      significant cardiac dysfunction. A renal angiography showed complete, likely
      thrombotic occlusion of the right renal artery. Renal MAG3 imaging showed minimal
      function of the affected kidney, and a nephrectomy secondary to medically
      uncontrollable hypertension and worsening cardiac dysfunction was performed. The
      child is developing normally in all aspects on follow-up evaluations at 6 months
      and 1 year of age. Reevaluation of the working diagnosis in neonates with
      hypertension can be necessary to optimize the outcome. The overall prognosis can
      be excellent even in newborns with profound cardiac and neurologic involvement.

PMID- 17200257
TI  - The status of academic general pediatrics: no longer endangered?
AB  - Our study objective was to assess the current state of general academic
      pediatrics in the United States. A confidential survey of division directors was
      conducted. At the beginning and end of the survey period, programs were called to
      verify the director's name. Of 199 divisions surveyed, 119 were returned. The
      number of physician and nonphysician division faculty has grown from a mean of
      12.1 (+/-8.2) and 1.7 (+/-1.8), respectively, 5 years ago to 15.6 (+/-11.7) and
      2.1 (+/-2.6). Over a 15- to 18-month period, 21% of programs had a change in
      division director leadership. Over 90% of divisions rated the clinical care and
      education missions as "very important," with research and advocacy thus rated by
      29% and 50%. Ninety-five percent of divisions have primary responsibility for
      residency continuity clinics, 51% residency program, and 64% medical student
      clerkship. The mean number of annual outpatient visits was 29,821 (26,487).
      Academic general pediatrics divisions have grown and play a large role in
      clinical care, education, and research at their institutions. There is a need for
      continued focus on recruitment, fellowship training, faculty development, and
      leadership development. Although these divisions are now well established, many
      continue to feel "endangered" because of funding uncertainties in supporting
      their missions.

PMID- 17200256
TI  - Childhood mental ability in relation to food intake and physical activity in
      adulthood: the 1970 British Cohort Study.
AB  - OBJECTIVE: The purpose of this work was to examine the relation of scores on
      tests of mental ability in childhood with food consumption and physical activity
      in adulthood. METHODS: Based on a cohort of >17,000 individuals born in Great
      Britain in 1970, 8282 had complete data for mental ability scores at 10 years of
      age and reported their food intake and physical activity patterns at 30 years of
      age. RESULTS: Children with higher mental ability scores reported significantly
      more frequent consumption of fruit, vegetables (cooked and raw), wholemeal bread,
      poultry, fish, and foods fried in vegetable oil in adulthood. They were also more
      likely to have a lower intake of chips (French fries), nonwholemeal bread, and
      cakes and biscuits. There was some attenuation in these associations after
      adjustment for markers of socioeconomic position across the life course, which
      included educational attainment, with statistical significance lost in some
      analyses. Higher mental ability was positively associated with exercise habit, in
      particular, intense activity (defined by being out of breath/sweaty). The
      associations between mental ability and these behaviors were similar in both men
      and women, and they were somewhat stronger for verbal than nonverbal ability.
      CONCLUSIONS: It is plausible that the skills captured by IQ tests, such as the
      ability to comprehend and reason, may be important in the successful management
      of a person's health behaviors.

PMID- 17200258
TI  - The use of the World Wide Web by medical journals in 2003 and 2005: an
      observational study.
AB  - OBJECTIVES: The 2- to 6-page print journal article has been the standard for 200
      years, yet this format severely limits the amount of detailed information that
      can be conveyed. The World Wide Web provides a low-cost option for posting
      extended text and supplementary information. It also can enhance the experience
      of journal editors, reviewers, readers, and authors through added functionality
      (eg, online submission and peer review, postpublication critique, and e-mail
      notification of table of contents.) Our aim was to characterize ways that
      journals were using the World Wide Web in 2005 and note changes since 2003.
      METHODS: We analyzed the Web sites of 138 high-impact print journals in 3 ways.
      First, we compared the print and Web versions of March 2003 and 2005 issues of 28
      journals (20 of which were randomly selected from the 138) to determine how often
      articles were published Web only and how often print articles were augmented by
      Web-only supplements. Second, we examined what functions were offered by each
      journal Web site. Third, for journals that offered Web pages for reader
      commentary about each article, we analyzed the number of comments and
      characterized these comments. RESULTS: Fifty-six articles (7%) in 5 journals were
      Web only. Thirteen of the 28 journals had no supplementary online content. By
      2005, several journals were including Web-only supplements in >20% of their
      papers. Supplementary methods, tables, and figures predominated. The use of
      supplementary material increased by 5% from 2% to 7% in the 20-journal random
      sample from 2003 to 2005. Web sites had similar functionality with an emphasis on
      linking each article to related material and e-mailing readers about activity
      related to each article. There was little evidence of journals using the Web to
      provide readers an interactive experience with the data or with each other.
      Seventeen of the 138 journals offered rapid-response pages. Only 18% of eligible
      articles had any comments after 5 months. CONCLUSIONS: Journal Web sites offer
      similar functionality. The use of online-only articles and online-only
      supplements is increasing.

PMID- 17200260
TI  - Infection in the first 2 years of life and autism spectrum disorders.
AB  - OBJECTIVE: The purpose of this work was to investigate the association between
      infections in the first 2 years and subsequent diagnosis of autism spectrum
      disorders. METHODS: We conducted a case-control study among children born at
      Kaiser Permanente Northern California from 1995 to 1999. Case subjects (n = 403)
      were children with an autism diagnosis recorded in Kaiser Permanente databases.
      Control subjects (n = 2100) were randomly sampled from the remaining children
      without autism and frequency matched to case subjects on gender, birth year, and
      birth hospital. Information on infections and covariates were obtained from
      Kaiser Permanente and birth certificate databases. RESULTS: Overall, infection
      diagnoses in the first 2 years of life were recorded slightly less often for
      children with autism than control children (95.0% vs 97.5%). Among specific
      diagnoses, upper respiratory infections were significantly less frequently
      diagnosed and genitourinary infections more frequently diagnosed in children with
      autism. In the first 30 days of life, the frequency of having an infection was
      slightly higher among children with autism (22.6% vs 18.7%). CONCLUSIONS:
      Children with subsequent diagnoses of autism do not have more overall infections
      in the first 2 years of life than children without autism. Data suggest that
      children with autism may have modestly elevated rates of infection in the first
      30 days and that, during the first 2 years, children with autism may be at higher
      risk for certain types of infections and lower risk for others. Additional
      studies that explore the associations between prenatal and early childhood
      infections and autism may help clarify the role of infection and the immune
      system in the etiology of autism spectrum disorder.

PMID- 17200259
TI  - Accuracy and interpretation of rapid influenza tests in children.
AB  - BACKGROUND: Influenza rapid antigen detection (rapid tests) can provide timely
      identification of infection and aid in clinical decision-making. Although the
      interpretation of test results depends on test characteristics and influenza
      prevalence, this information is limited in routine clinical practice. OBJECTIVE:
      We sought to assess the times at which rapid tests are most predictive of
      influenza infection. METHODS: The New Vaccine Surveillance Network enrolled
      children aged < 5 years who were hospitalized with respiratory symptoms or fever
      from October 2000 through September 2004. Nasal and throat swabs were obtained,
      and influenza virus was detected by culture and reverse-transcription polymerase
      chain reaction. Provider-ordered rapid influenza tests were compared with the
      criterion standard (culture and reverse-transcription polymerase chain reaction)
      to determine their sensitivity and specificity. The New Vaccine Surveillance
      Network also enrolled children in outpatient settings during the 2002-2003 and
      2003-2004 influenza seasons and determined the weekly influenza prevalence among
      symptomatic children. Trends in weekly predictive values of the rapid tests were
      estimated over the influenza seasons. RESULTS: Rapid influenza tests had an
      overall sensitivity of 63% and specificity of 97%. In 2002-2003, the prevalence
      of influenza in symptomatic outpatient children peaked at 21% and stayed above
      10% for approximately 4 weeks. In contrast, in 2003-2004, influenza prevalence
      peaked at 60% and remained above 20% for approximately 6 weeks. The positive
      predictive value of the rapid tests approached 80% when influenza prevalence was
      > or = 15% but decreased to < 70% when influenza prevalence was < 10%.
      CONCLUSIONS: Influenza prevalence varies between and within seasons. On the basis
      of our estimates, rapid tests are of limited use when prevalence is < 10%. The
      appropriate interpretation of rapid influenza tests requires local influenza
      surveillance and timely communication of this information to the practitioners.

PMID- 17200261
TI  - To what extent do pediatricians accept computer-based dosing suggestions?
AB  - OBJECTIVE: Pediatric medication errors occur frequently among hospitalized
      patients and are often related to dosing. Computerized physician order entry
      systems with decision support can decrease dosing errors, as well as other types
      of errors; however, their use in pediatrics has not been extensively studied. Our
      objective was to determine physician acceptance of dosing and frequency decision
      support elements in an inpatient pediatric computerized physician order entry
      system at 1 academic medical center. PATIENTS AND METHODS: We performed a
      retrospective analysis of all electronic medication orders entered for pediatric
      inpatients at a large, urban teaching hospital between April 15, 2004, and
      December 31, 2004. Rates of physician acceptance of computerized physician order
      entry system-generated dosing and frequency suggestions were determined. RESULTS:
      We analyzed 54,413 orders in the computerized physician order entry system, of
      which 27,313 orders had dosing or frequency decision support. Of the orders with
      decision support, approximately one third (8822) were accepted exactly by
      prescribers. Of the 18,491 remaining orders, 8708 were changed for dose, 2466 for
      frequency, and 7317 for both. Among the 18,491 orders that were changed, the
      majority 11,322 deviated by a substantial amount (>50%) from the total daily dose
      initially suggested by the decision support feature. Overall, patient weight was
      missing 31.3% of the time, although patient age alone sometimes was sufficient
      for the computer to make a dosing suggestion. CONCLUSIONS: Although dosing
      decision support systems have the potential to improve care, more work needs to
      be done to determine and optimize their effectiveness. Commercial vendors of
      dosing knowledge bases need to deliver effective products, because most health
      care organizations will not have the resources to customize decision support
      rules.

PMID- 17200262
TI  - Prevention of pediatric medication errors by hospital pharmacists and the
      potential benefit of computerized physician order entry.
AB  - OBJECTIVES: The purpose of this work was to characterize medication errors and
      adverse drug events intercepted by a system of pediatric clinical pharmacists and
      to determine whether the addition of a computerized physician order entry system
      would improve medication safety. METHODS: The study included 16,938 medication
      orders for 678 admissions to the pediatric units of a large academic community
      hospital. Pediatric clinical pharmacists reviewed medication orders and monitored
      subsequent medication use. Medication errors and adverse drug events were
      identified by daily review of documentation, voluntary reporting, and
      solicitation. Each potentially harmful medication error was judged whether or not
      it was intercepted and, if not, whether it would have been captured by a
      computerized physician order entry system. RESULTS: Overall, 865 medication
      errors occurred, corresponding with a rate of 5.2 per 100 medication orders. A
      near-miss rate of 0.96% and a preventable adverse drug event rate of 0.09% were
      observed. Overall, 78% of potentially harmful prescribing errors were
      intercepted; however, none of the potentially harmful errors occurring at
      administration was intercepted and accounted for 50% of preventable adverse drug
      events. A computerized physician order entry system could capture additional
      potentially harmful prescribing and transcription errors (54%-73%) but not
      administration errors (0% vs 6%). CONCLUSIONS: A system of pediatric clinical
      pharmacists effectively intercepted inpatient prescribing errors but did not
      capture potentially harmful medication administration errors. The addition of a
      computerized physician order entry system to pharmacists is unlikely to prevent
      administration errors, which pose the highest risk of patient injury.

PMID- 17200263
TI  - Caregiver health literacy and the use of child health services.
AB  - OBJECTIVES: Eighty million US adults have low health literacy, a risk factor for
      increased health care use among adults. The purpose of this work was to assess
      the association between caregiver health literacy and the use and cost of child
      health services. METHODS: We conducted a cross-sectional study of caregiver-child
      dyads from a sample of children aged 12 months to 12 years presenting to the
      pediatric emergency department of an urban, public hospital. Caregiver health
      literacy was measured by the Short Test of Functional Health Literacy in their
      preferred language (English or Spanish). Child health care use was measured by a
      12-month retrospective review of the public hospital system's electronic database
      and of state Medicaid billing records for 4 types of visits: preventive care,
      urgent care, emergency care, and hospital care. Cost of child health care use was
      provided by Medicaid billing records. Multivariate analysis included caregiver
      education, age, and language proficiency, as well as child age, special health
      care needs, ethnicity, and health-insurance coverage. RESULTS: A total of 290
      dyads were enrolled in the study. Twenty-two percent of caregivers had low
      (inadequate or marginal) health literacy. Caregivers with low health literacy
      were more likely to have less than a high school education, to have limited
      English proficiency, and to have been born outside the United States. There were
      no differences in health care use or cost between children of caregivers with low
      health literacy and children of caregivers with adequate health literacy. Three
      caregiver characteristics were associated with increased use of child health care
      services: born outside the United States, age at child's birth <24 years, and
      limited English proficiency. CONCLUSIONS: One in 5 caregivers of young children
      has low health literacy. Caregiver health literacy, however, was not associated
      with disparities in the use of child health services in this inner-city, ethnic
      minority population.

PMID- 17200264
TI  - At what age can children report dependably on their asthma health status?
AB  - OBJECTIVE: This study examined psychometric properties and feasibility issues
      surrounding child-reported asthma health status data. METHODS: In separate
      interviews, parents and children completed 3 visits. Child questionnaires were
      interviewer administered. The primary instrument was the Children's Health Survey
      for Asthma-Child Version, used to compute 3 scales (physical health, activities,
      and emotional health). The following were assessed: reliability (internal
      consistency and test-retest reliability), validity (general health status,
      symptom burden, and lung function), and feasibility (completion time, missing
      data, and inconsistent responses). RESULTS: A total of 414 parent-child pairs
      completed the study (mean child age: 11.5 years). Reliability estimates for the
      activities and emotional health scales were > .70 in all but 1 age category; 5 of
      9 age groups had acceptable internal consistency ratings (> or = .70) for the
      physical health scale. Cronbach's alpha tended to increase with child age. In
      general, test-retest correlations between forms and intraclass correlation
      coefficients were strong for all ages but tended to increase with child age.
      Correlations between forms ranged from .57 (7-year-old subjects, physical health)
      to .96 (14-year-old subjects, activities). Intraclass correlation coefficients
      ranged from .76 (13-year-old subjects, emotional health) to .94 (15-16-year-old
      subjects, physical health). Children with less symptom burden reported higher
      mean Children's Health Survey for Asthma-Child Version scores (indicating better
      health status) for each scale, at significant levels for nearly all age groups.
      Children's Health Survey for Asthma-Child Version completion times decreased from
      12.9 minutes at age 7 to 6.9 minutes at age 13. CONCLUSIONS: This research
      indicates that children with asthma as young as 7 may be dependable and valuable
      reporters of their health. Data quality tends to improve with age.

PMID- 17200265
TI  - Will pediatricians adopt the new rotavirus vaccine?
AB  - OBJECTIVES: Our objective was to determine the following among US pediatricians:
      (1) perceptions regarding burden of rotavirus disease and need for a vaccine; (2)
      intentions for recommending a newly licensed rotavirus vaccine; (3) perceived
      barriers to implementation; and (4) factors associated with plans for vaccine
      adoption. PATIENTS AND METHODS: A network of 431 pediatricians was recruited from
      a random sample of American Academy of Pediatrics' members. The network was
      designed to be representative of the American Academy of Pediatrics with respect
      to region of the country, practice type, and practice setting. During January and
      February 2006, physicians were surveyed by Internet or mail. The survey contained
      a paragraph summarizing results of the new rotavirus vaccine trial. Respondents
      were asked about intentions to use the vaccine and anticipated barriers. RESULTS:
      The survey response rate was 71%. Of the respondents, 52% strongly agreed and 37%
      somewhat agreed with the need for a rotavirus vaccine. If recommended for routine
      use, 50% would strongly recommend and 34% would recommend but not strongly; 52%
      would begin to use within 6 months and 27% from 6 months to 1 year. The top 3
      "definite" barriers to implementation included concerns about uniform coverage of
      vaccine by insurers, lack of adequate reimbursement, and parental reluctance
      because of withdrawal of previous rotavirus vaccine. In multivariate analysis,
      factors associated with very likely adoption of the vaccine included perception
      of a high burden of rotavirus disease and a high level of confidence in
      prelicensure studies of vaccine safety. The presence of physician concerns about
      safety of the new vaccine and the perception of parental concerns about vaccine
      safety in general were negatively associated with adoption. CONCLUSIONS: The
      majority of pediatricians reported willingness to implement the new rotavirus
      vaccine, most within 6 months. Major barriers to optimal implementation included
      provider concerns about reimbursement issues and parental acceptance of the
      vaccine.

PMID- 17200266
TI  - Efficacy, immunogenicity, and safety of a pentavalent human-bovine (WC3)
      reassortant rotavirus vaccine at the end of shelf life.
AB  - BACKGROUND: Rotavirus is the leading cause of dehydrating acute gastroenteritis
      in infants worldwide. Previous studies of a live pentavalent human-bovine
      reassortant rotavirus vaccine have shown it to be efficacious across a range of
      potencies. OBJECTIVE: Our goal was to evaluate the efficacy, immunogenicity, and
      safety of pentavalent rotavirus vaccine at the end of shelf life in healthy
      infants. PATIENTS AND METHODS: During 2002-2004, 1312 healthy infants
      approximately 6 to 12 weeks old from the United States (47%) and Finland (53%)
      were randomly assigned to receive 3 oral doses of vaccine (vaccine at
      approximately 1.1 x 10(7) infectious U per dose) or placebo approximately 4 to 10
      weeks apart. Infants were to be followed for acute gastroenteritis through 1
      rotavirus season after vaccination and for adverse events postvaccination.
      RESULTS: Three doses of pentavalent rotavirus vaccine at the end of shelf life
      demonstrated efficacy against rotavirus gastroenteritis caused by human G
      serotypes included in the vaccine (G1-G4). Efficacy against severe rotavirus
      gastroenteritis was 100%, and efficacy against any rotavirus gastroenteritis
      regardless of severity was 72.5%. A threefold rise in G1 serum neutralizing was
      observed in 57% and in anti-rotavirus immunoglobulin A in 96% of pentavalent
      rotavirus vaccine recipients. No statistically significant increase in vomiting,
      diarrhea, or irritability was observed among pentavalent rotavirus vaccine
      recipients compared with placebo recipients within the 7-day period from each
      dose. A statistically significant increase in fevers (> or = 100.5 degrees F,
      rectal equivalent) was observed among pentavalent rotavirus vaccine recipients
      compared with placebo recipients after dose 1. CONCLUSIONS: This pentavalent
      human-bovine rotavirus vaccine was generally well tolerated, efficacious, and
      immunogenic at the end of shelf life.

PMID- 17200267
TI  - Cystic fibrosis diagnosed after 2 months of age leads to worse outcomes and
      requires more therapy.
AB  - OBJECTIVE: Newborn screening for cystic fibrosis remains controversial because
      improved pulmonary function has not been established. Studies to date have not
      accounted for differences in treatments delivered to clinically diagnosed
      children and newborn-screened controls. Here, we compare outcomes and treatment
      of patients clinically diagnosed within the newborn-screening reporting window
      (early-clinically diagnosed), those presenting after this period (late-clinically
      diagnosed), and patients diagnosed by newborn screening. PATIENTS AND METHODS: In
      a cross-sectional analysis of cohorts retrospectively ascertained, patients who
      were homozygous deltaF508 with cystic fibrosis, attending specialist cystic
      fibrosis centers, and 1 to 10 years of age between 2000 and 2002 were identified
      from the United Kingdom Cystic Fibrosis Database and stratified into newborn
      screened, early-clinically diagnosed, or late-clinically diagnosed cohorts. Two
      analyses were performed: (1) after restricting to the most recent year of data
      collection, early-clinically diagnosed and late-clinically diagnosed cohorts were
      matched to newborn-screened patients by patient age and year of data collection
      (133 patients per cohort were identified); and (2) for all years of data
      collection, annual sets of data for early-clinically diagnosed and late
      clinically diagnosed patients were matched to newborn-screened patients by
      patient age and year of data collection (291 data sets per cohort were
      identified). Median height and weight z scores, proportion of patients with
      height and weight <10th percentile, prevalence of chronic Pseudomonas aeruginosa
      infection, Shwachman-Kulczyki morbidity scores, percent predicted forced
      expiratory volume in 1 second, and numbers of long-term therapies were compared.
      RESULTS: In both analyses, newborn screening was associated with higher height z
      score, higher Shwachman-Kulczyki score, lower likelihood of height <10th
      percentile, and fewer long-term therapies compared with late-clinically diagnosed
      patients. No other differences were found. CONCLUSIONS: Newborn screening was
      associated with improved growth, reduced morbidity, and reduced therapy, yet
      generated equivalent pulmonary outcome compared with late clinical diagnosis,
      suggesting that newborn screening may slow cystic fibrosis lung disease
      progression.

PMID- 17200268
TI  - No improvement in outcome of nationwide extremely low birth weight infant
      populations between 1996-1997 and 1999-2000.
AB  - OBJECTIVE: Our goal was to investigate whether outcome in extremely low birth
      weight infants changes over time in Finland. PATIENTS AND METHODS: All infants
      with a birth weight <1000 g born in Finland in 1996-1997 and 1999-2000 were
      included in the study. Perinatal and follow-up data were collected in a national
      extremely low birth weight infant research register. Data concerning cerebral
      palsy and visual impairment were obtained from hospitals, the national discharge,
      and visual impairment registers. RESULTS: A total of 529 and 511 extremely low
      birth weight infants were born during 1996-1997 and 1999-2000. No changes were
      detected in prenatal, perinatal, neonatal, and postneonatal mortality rates
      between the periods. The survival rates including stillborn infants were 40% and
      44%. The incidence of respiratory distress syndrome and septicemia increased from
      1996-1997 to 1999-2000 (75% vs 83% and 23% vs 31%). The overall incidence of
      intraventricular hemorrhage increased (29% vs 37%), but the incidence of
      intraventricular hemorrhage grades 3 through 4 did not (16% vs 17%). The rates of
      oxygen dependency at the age corresponding with 36 gestational weeks, retinopathy
      of prematurity stages 3 to 5, cerebral palsy, and severe visual impairment did
      not change. Mortality remained higher in 1 university hospital area during both
      periods compared with the other 4 areas, but no regional differences in morbidity
      were detected during the later period. CONCLUSIONS: No significant changes were
      detected in birth or mortality rate in extremely low birth weight infants born in
      Finland during the late 1990s, but some neonatal morbidities seemed to increase.
      Regional differences in mortality were detected in both cohorts. Repeated long
      term follow-up studies on geographically defined very preterm infant cohorts are
      needed for establishing reliable outcome data of current perinatal care. Regional
      differences warrant thorough audits to assess causalities.

PMID- 17200269
TI  - Improved neurodevelopmental outcomes for extremely low birth weight infants in
      2000-2002.
AB  - BACKGROUND: Neurodevelopmental impairment of extremely low birth weight infants
      increased in the 1990s. Modern therapeutic changes may have influenced more
      recent neonatal outcomes. OBJECTIVE: We sought to compare neonatal therapies and
      outcomes among all extremely low birth weight infants born in 2000-2002 (period
      III) to 2 previous periods: 1982-1989 (period I) and 1990-1999 (period II).
      METHODS: The population included 496 extremely low birth weight infants born at
      our perinatal center during period I, 749 during period II, and 233 during period
      III. Therapies, rates of death, and survival with and without impairment at 20
      months' corrected age were compared. RESULTS: Between periods I and II, survival
      increased from 49% to 68% as did neonatal morbidity. This resulted in increased
      survival without impairment but also increased survival with impairment. Changes
      in therapy during period III included an increase in antenatal steroid use and a
      decrease in postnatal steroid use, although the rate of chronic lung disease did
      not change. Sepsis decreased, as did severe intraventricular hemorrhage. On
      follow-up, the rate of cerebral palsy decreased from 13% to 5%, resulting in a
      decrease in neurodevelopmental impairment from 35% to 23%. As a result, during
      period III versus II, survival without impairment increased, whereas survival
      with impairment decreased. CONCLUSION: Since 2000, neurodevelopmental impairment
      has decreased among extremely low birth weight infants. A variety of perinatal
      and neonatal factors were associated with the improved outcomes including
      increased antenatal steroid use and cesarean section delivery, as well as
      decreased sepsis, severe cranial ultrasound abnormalities, and postnatal steroid
      use despite no change in the rate of chronic lung disease.

PMID- 17200270
TI  - Is a "wage-payment" model for research participation appropriate for children?
AB  - OBJECTIVE: Our goal was to evaluate the applicability of a "wage-payment" model
      to inducements for children to participate in research. SUBJECTS AND METHODS: We
      interviewed 42 children and adolescents between the ages of 4 and 16 years who
      had diabetes, asthma, seizures, or no chronic medical condition. The interview
      explored hypothetical participation decisions for up to 4 research scenarios. To
      evaluate factors that would influence children and adolescents' decision-making
      for research participation, we probed for the impact of monetary and other
      incentives. The interviews were transcribed and coded for specific themes related
      to money or other rewards and incentives. RESULTS: Older children, mainly those
      >9 years of age, showed an appreciation for the role and value of money through
      (a) an accurate concept of the material value of money in society or (b) asking
      for a realistic amount of money in exchange for their research participation.
      Younger children, primarily those <9 years of age, showed an inability to
      appreciate the role and value of money by: (a) asking for excessive monetary
      amounts that bore no relationship to the sum warranted by participation; (b)
      having no concept of what that money could buy; (c) not comprehending the meaning
      of a wage as earning a reward for working; or (d) justifying proposed amounts
      with reasons unrelated to the time and effort involved. CONCLUSIONS: An age
      appropriate token of appreciation as an inducement for research participation is
      appropriate for the younger child who is <9 years old, because they generally
      have an inadequate understanding of the value of money and, therefore, the
      meaning of a wage. A wage-payment model for compensating older children (>9 years
      of age) and adolescents for the time and effort of research participation is
      appropriate because they generally understand the meaning and value of a wage.

PMID- 17200271
TI  - Effects of selective serotonin reuptake inhibitors and venlafaxine during
      pregnancy in term and preterm neonates.
AB  - OBJECTIVES: Our goals were to (a) describe neonatal behavioral signs in a group
      of newborns exposed in utero to selective serotonin reuptake inhibitors or
      venlafaxine at the time of delivery, (b) compare the rate of neonatal behavioral
      signs, prematurity, and admission to specialized neonatal care between a group of
      exposed and unexposed newborns, and (c) compare the effects in exposed preterm
      and term newborns. PATIENTS AND METHODS: This was a retrospective cohort study
      including mothers taking selective serotonin reuptake inhibitors or venlafaxine
      during the third trimester and mothers who were not taking any antidepressants,
      psychotropic agents, or benzodiazepines at the time of delivery of their
      newborns. Neonatal behavioral signs included central nervous, respiratory, and
      digestive systems, as well as hypoglycemia and the need for phototherapy.
      RESULTS: Seventy-six mothers taking antidepressants and 90 untreated mothers and
      their newborns were analyzed. Smoking, alcohol intake, and substance abuse were
      more frequent among treated mothers. In infants in the exposed group, signs
      involving the central nervous and the respiratory systems were often observed
      (63.2% and 40.8%, respectively). These signs appeared during the first day of
      life, with a median duration of 3 days for exposed newborns. The signs resolved
      in 75% of cases within 3 to 5 days for term and premature newborns, respectively.
      All exposed premature newborns presented behavioral manifestations compared with
      69.1% of term exposed newborns. Median length of stay was almost 4 times longer
      for exposed premature newborns than for those who were unexposed (14.5 vs 3.7
      days). CONCLUSIONS: Neonatal behavioral signs were frequently found in exposed
      newborns, but symptoms were transient and self-limited. Premature infants could
      be more susceptible to the effects of selective serotonin reuptake inhibitors and
      venlafaxine.

PMID- 17200272
TI  - Low-income uninsured children with special health care needs: why aren't they
      enrolled in public health insurance programs?
AB  - OBJECTIVE: We examined potential barriers to enrollment in public programs among
      low-income children with special health care needs who are uninsured. Barriers
      considered include parents not knowing about the Medicaid and State Children's
      Health Insurance programs, not believing that their child is eligible for public
      coverage, not perceiving the enrollment processes as easy, and not wanting to
      enroll their child in a public program. METHODOLOGY: The source of data is the
      2001 National Survey of Children With Special Health Care Needs. A series of 5
      questions about the child's health needs, known as the Children With Special
      Health Care Needs Screener, was used to identify children with special health
      care needs. Uninsurance is defined as having no insurance coverage at the time of
      the survey. Low-income families are defined as those with household incomes below
      200% of the federal poverty level. The analytic sample consists of 968 low-income
      uninsured children with special health care needs. We examined the socioeconomic
      and demographic characteristics of the sample, the reasons the children lack
      coverage, and the awareness and perception measures, both individually and
      combined as a summary measure. RESULTS: Many low-income parents with uninsured
      children with special health care needs do not have full information about
      Medicaid and State Children's Health Insurance programs or do not have positive
      perceptions of the application processes. Although 93.5% had heard of at least 1
      of the 2 programs, only 54.6% believed that their child was eligible for public
      coverage, and just 48.1% believed that the application processes were easy.
      Almost all said that they would enroll their child if told he or she was eligible
      for public coverage. CONCLUSIONS: Understanding why uninsured children with
      special health care needs do not participate in public programs is important,
      because these programs have the potential to cover almost all of this population.
      Initiatives to increase enrollment should yield real dividends given that the
      vast majority of low-income uninsured children with special health care needs
      have parents who say they would enroll their children in public coverage.

PMID- 17200273
TI  - Binge drinking and associated health risk behaviors among high school students.
AB  - OBJECTIVES: Underage drinking contributes to the 3 leading causes of death
      (unintentional injury, homicide, and suicide) among persons aged 12 to 20 years.
      Most adverse health effects from underage drinking stem from acute intoxication
      resulting from binge drinking. Although binge drinking, typically defined as
      consuming > or = 5 drinks on an occasion, is a common pattern of alcohol
      consumption among youth, few population-based studies have focused specifically
      on the characteristics of underage binge drinkers and their associated health
      risk behaviors. METHODS: We analyzed data on current drinking, binge drinking,
      and other health risk behaviors from the 2003 National Youth Risk Behavior
      Survey. Prevalence estimates and 95% confidence intervals were calculated by
      using SAS and SUDAAN statistical software. Logistic regression was used to
      examine the associations between different patterns of alcohol consumption and
      health risk behaviors. RESULTS: Overall, 44.9% of high school students reported
      drinking alcohol during the past 30 days (28.8% binge drank and 16.1% drank
      alcohol but did not binge drink). Although girls reported more current drinking
      with no binge drinking, binge-drinking rates were similar among boys and girls.
      Binge-drinking rates increased with age and school grade. Students who binge
      drank were more likely than both nondrinkers and current drinkers who did not
      binge to report poor school performance and involvement in other health risk
      behaviors such as riding with a driver who had been drinking, being currently
      sexually active, smoking cigarettes or cigars, being a victim of dating violence,
      attempting suicide, and using illicit drugs. A strong dose-response relationship
      was found between the frequency of binge drinking and the prevalence of other
      health risk behaviors. CONCLUSIONS: Binge drinking is the most common pattern of
      alcohol consumption among high school youth who drink alcohol and is strongly
      associated with a wide range of other health risk behaviors. Effective
      intervention strategies (eg, enforcement of the minimum legal drinking age,
      screening and brief intervention, and increasing alcohol taxes) should be
      implemented to prevent underage alcohol consumption and adverse health and social
      consequences resulting from this behavior.

PMID- 17200274
TI  - Adverse associations of sleep problems in Australian preschoolers: national
      population study.
AB  - OBJECTIVE: In contrast to school-aged children, the impact of sleep problems in
      preschool-aged children is not well documented. We aimed to determine
      relationships between preschool-aged child sleep problems and child behavior;
      health-related quality of life; verbal, preliteracy, and early numeracy skills;
      diagnosis of attention-deficit/hyperactivity disorder; and injury. PARTICIPANTS
      AND METHODS: Participants included families (n = 4983) participating in the first
      wave of the Longitudinal Study of Australian Children, a nationally
      representative study of Australian children aged 4 to 5 years surveyed from March
      to November 2004. Measures consisted of a primary caregiver's report of whether
      their child had a sleep problem (none versus mild versus moderate/severe);
      specific sleep patterns occurring > or = 4 nights per week; health-related
      quality of life (by using the Pediatric Quality of Life Inventory 4.0); behavior
      (by using the Strengths and Difficulties Questionnaire) and parent-reported
      diagnosis of attention-deficit/hyperactivity disorder; and injury requiring
      medical attention in the past 12 months. Tests of receptive vocabulary and
      preliteracy/numeracy skills (by using the Who Am I? developmental assessment and
      the adapted Peabody Picture Vocabulary Test, 3rd Edition) were directly
      administered to each child. RESULTS: Sleep problems were common, and compared
      with children without sleep problems, children with sleep problems had poorer
      child health-related quality of life, more behavior problems, and higher rates of
      attention-deficit/hyperactivity disorder. Difficulty going to sleep and morning
      tiredness had greater adverse associations than snoring or night waking.
      CONCLUSIONS: Given that sleep problems are very common, the adverse outcomes
      shown here could affect the transition to school for a very large number of
      preschoolers.

PMID- 17200275
TI  - Pediatric hospital and intensive care unit capacity in regional disasters:
      expanding capacity by altering standards of care.
AB  - BACKGROUND: Federal planners have suggested that one strategy to accommodate
      disaster surges of 500 inpatients per million population would involve altering
      standards of care. No data are available indicating the extent of alterations
      necessary to meet disaster surge targets. OBJECTIVE: Our goal was to, in a Monte
      Carlo simulation study, determine the probability that specified numbers of
      children could be accommodated for PICU and non-ICU hospital care in a disaster
      by a set of strategies involving altered standards of care. METHODS: Simulated
      daily vacancies at each hospital in New York City were generated as the
      difference between peak capacity and daily occupancy (generated randomly from a
      normal distribution on the basis of empirical data for each hospital).
      Simulations were repeated 1000 times. Capacity for new patients was explored for
      normal standards of care, for expansion of capacity by a discretionary 20%
      increase in vacancies by altering admission and discharge criteria, and for more
      strictly reduced standards of care to double or quadruple admissions for each
      vacancy. Resources were considered to reliably serve specified numbers of
      patients if that number could be accommodated with a probability of 90%. RESULTS:
      Providing normal standards of care, hospitals in New York City would reliably
      accommodate 250 children per million age-specific population. Hypothetical strict
      reductions in standards of care would reliably permit hospital care of 500
      children per million, even if the disaster reduced hospital resources by 40%. On
      the basis of historical experience that as many as 30% of disaster casualties may
      be critically ill or injured, existing pediatric intensive care beds will
      typically be insufficient, even with modified standards of care. CONCLUSIONS:
      Extending resources by hypothetical alterations of standards of care would
      usually satisfy targets for hospital surge capacity, but ICU capacity would
      remain inadequate for large disasters.

PMID- 17200276
TI  - Adolescent depression screening in primary care: feasibility and acceptability.
AB  - OBJECTIVE: Despite available depression treatments, only one fourth to one third
      of depressed adolescents are receiving care. The problem of underdiagnosis and
      underreferral might be redressed if assessment of suicidality and depression
      became a more formal part of routine pediatric care. Our purpose for this study
      was to explore the feasibility and acceptability of implementing adolescent
      depression screening into clinical practice. METHODS: In this study we
      implemented a 2-stage adolescent identification protocol, a first-stage pen-and
      paper screen and a second-stage computerized assessment, into a busy primary care
      pediatric practice. Providers tracked the number of eligible patients screened at
      both health maintenance and urgent care visits and provided survey responses
      regarding the burden that screening placed on the practice and the effect on
      patient/parent-provider relationships. RESULTS: Seventy-nine percent of
      adolescent patients presenting for health maintenance visits were screened, as
      were the majority of patients presenting for any type of visit. The average
      completion time for the paper screen was 4.6 minutes. Providers perceived parents
      and patients as expressing more satisfaction than dissatisfaction with the
      screening procedures and that the increased time burden could be handled. All
      providers wished to continue using the paper screen at the conclusion of the
      protocol. CONCLUSIONS: Instituting universal systematic depression screening in a
      practice with a standardized screening instrument met with little resistance by
      patients and parents and was well perceived and accepted by providers.

PMID- 17200277
TI  - New developments in the treatment of hypoplastic left heart syndrome.
AB  - In the current decade, the prognosis of newborns with hypoplastic left heart
      syndrome, previously considered a uniformly fatal condition, has dramatically
      improved through refinement of rapidly evolving treatment strategies. These
      strategies include various modifications of staged surgical reconstruction,
      orthotopic heart transplantation, and hybrid palliation using ductal stenting and
      bilateral pulmonary artery banding. The variety of treatment approaches are based
      on different surgical philosophies, and each approach has its unique advantages
      and disadvantages. Nonetheless, multiple experienced centers have reported
      improved outcomes in each one of those modalities. The purpose of this review is
      to outline recent developments in the array of currently available management
      strategies for neonates with hypoplastic left heart syndrome. Because the vast
      majority of deaths in this patient population occur within the first months of
      life, the focus of the review will be evaluation of the impact of these
      management strategies on survival in the neonatal and infant periods.

PMID- 17200278
TI  - Will esophageal impedance replace pH monitoring?
AB  - Esophageal impedance, a technique based on the fact that the passage of a bolus
      changes the impedance between esophageal segments, is being used more and more.
      Multiple esophageal impedance combined with pH monitoring is advocated to become
      the preferred technique to measure acid and nonacid gastroesophageal reflux.
      Compared with pH monitoring, impedance has the advantage of being independent of
      pH and, as a consequence, is better adapted to measure reflux (especially in the
      postprandial period when reflux is buffered) and detect symptoms associated with
      nonacid- or weakly acid-reflux episodes. Conversely, the analysis of an impedance
      tracing requires more time and knowledge than a pH tracing and is possibly
      subjected to higher interobserver variability. Day-to-day reproducibility and
      interobserver variability are considerable. Episodes detected only by pH
      monitoring or impedance are numerous in pediatrics; therefore, pH monitoring and
      impedance should be associated in analyses of multiple esophageal impedance
      combined with pH monitoring. Up to now, there has been a striking absence of
      literature showing attempts to link data from diagnostic procedures to clinical
      outcome in symptomatic patients. Furthermore, data suggesting that impedance does
      offer a clear-cut benefit in pediatric clinical routine are missing. High cost of
      the material and the investment in time necessary for interpretation of the
      recording remain a handicap. However, because pH monitoring is part of impedance
      technology, it is likely that the latter will soon replace pH monitoring despite
      the current need of scientific evidence demonstrating a relation between
      symptoms, esophageal damage or response to reflux treatment, and results of
      multiple esophageal impedance combined with pH monitoring.

PMID- 17200279
TI  - Legal and ethical considerations: risks and benefits of postpartum depression
      screening at well-child visits.
AB  - Pediatric professionals are being asked to provide an increasing array of
      services during well-child visits, including screening for psychosocial and
      family issues that may directly or indirectly affect their pediatric patients.
      One such service is routine screening for postpartum depression at pediatric
      visits. Postpartum depression is an example of a parental condition that can have
      serious negative effects for the child. Because it is a maternal condition, it
      raises a host of ethical and legal questions about the boundaries of pediatric
      care and the pediatric provider's responsibility and liability. In this article
      we discuss the ethical and legal considerations of, and outline the risks of
      screening or not screening for, postpartum depression at pediatric visits. We
      make recommendations for pediatric provider education and for the roles of
      national professional organizations in guiding the process of defining the
      boundaries of pediatric care.

PMID- 17200280
TI  - Identifying children with autism early?

PMID- 17200281
TI  - Stimulant-drug therapy for attention-deficit disorder (with or without
      hyperactivity) and sudden cardiac death.

PMID- 17200282
TI  - The meaning of "early" diagnosis in a new era of cystic fibrosis care.

PMID- 17200283
TI  - The limits of viability and the uncertainty of neuroprotection: challenges in
      optimizing outcomes in extreme prematurity.

PMID- 17200284
TI  - Access to optimal emergency care for children.
AB  - Millions of pediatric patients require some level of emergency care annually, and
      significant barriers limit access to appropriate services for large numbers of
      children. The American Academy of Pediatrics has a strong commitment to
      identifying barriers to access to emergency care, working to surmount these
      obstacles, and encouraging, through education and system changes, improved levels
      of emergency care available to all children.

PMID- 17200285
TI  - Cord blood banking for potential future transplantation.
AB  - In recent years, umbilical cord blood, which contains a rich source of
      hematopoietic stem and progenitor cells, has been used successfully as an
      alternative allogeneic donor source to treat a variety of pediatric genetic,
      hematologic, immunologic, and oncologic disorders. Because there is diminished
      risk of graft-versus-host disease after transplantation of cord stem cells using
      matched related donors, the use of less-than-completely matched HLA cord blood
      stem cells may incur less risk of graft-versus-host disease than mismatched cells
      from either a related or unrelated "walking" donor, although this remains to be
      proven. Gene-therapy research involving modification of autologous cord blood
      stem cells for the treatment of childhood genetic disorders, although
      experimental at the present time, may prove to be of value. These scientific
      advances have resulted in the establishment of not-for-profit and for-profit cord
      blood-banking programs for allogeneic and autologous cord blood transplantation.
      Many issues confront institutions that wish to establish or participate in such
      programs. Parents often seek information from their physicians about this new
      biotechnology option. This document is intended to provide information to guide
      physicians in responding to parents' questions about cord blood donation and
      banking and the types and quality of cord blood banks. Provided also are
      recommendations about appropriate ethical and operational standards, including
      informed consent policies, financial disclosures, and conflict-of-interest
      policies for physicians, institutions, and organizations that operate or have a
      relationship with cord blood-banking programs.

PMID- 17200286
TI  - Prevention of rotavirus disease: guidelines for use of rotavirus vaccine.
AB  - On February 3, 2006, a bovine-based pentavalent rotavirus vaccine (RotaTeq, Merck
      & Co Inc, Whitehouse Station, NJ) was licensed by the US Food and Drug
      Administration for use in infants in the United States. The American Academy of
      Pediatrics recommends routine immunization of infants with 3 doses of pentavalent
      rotavirus vaccine administered orally at 2, 4, and 6 months of age. The first
      dose should be administered between 6 and 12 weeks of age; immunization should
      not be initiated for infants older than 12 weeks of age. Subsequent doses should
      be administered at 4- to 10-week intervals, and all 3 doses of vaccine should be
      administered by 32 weeks of age. Pentavalent rotavirus vaccine can be
      coadministered with other childhood vaccines. Pentavalent rotavirus vaccine is
      contraindicated for infants with a serious allergic reaction to any vaccine
      component or to a previous dose of vaccine.

PMID- 17200287
TI  - The importance of play in promoting healthy child development and maintaining
      strong parent-child bonds.
AB  - Play is essential to development because it contributes to the cognitive,
      physical, social, and emotional well-being of children and youth. Play also
      offers an ideal opportunity for parents to engage fully with their children.
      Despite the benefits derived from play for both children and parents, time for
      free play has been markedly reduced for some children. This report addresses a
      variety of factors that have reduced play, including a hurried lifestyle, changes
      in family structure, and increased attention to academics and enrichment
      activities at the expense of recess or free child-centered play. This report
      offers guidelines on how pediatricians can advocate for children by helping
      families, school systems, and communities consider how best to ensure that play
      is protected as they seek the balance in children's lives to create the optimal
      developmental milieu.

PMID- 17200288
TI  - Preventing and treating homesickness.
AB  - Homesickness is the distress and functional impairment caused by an actual or
      anticipated separation from home and attachment objects such as parents. It is
      characterized by acute longing and preoccupying thoughts of home. Almost all
      children, adolescents, and adults experience some degree of homesickness when
      they are apart from familiar people and environments. Pediatricians and other
      health care professionals are in a unique position to assist families in
      understanding the etiology, prevention, and treatment of homesickness. In the
      case of planned separations, such as summer camp, techniques are provided that
      may aid in prevention. In the case of unanticipated or traumatic separations,
      such as hospitalization, effective treatment strategies are available.

PMID- 17200289
TI  - Office-based counseling for unintentional injury prevention.
AB  - Unintentional injuries are the leading cause of death for children older than 1
      year. Pediatricians should include unintentional injury prevention as a major
      component of anticipatory guidance for infants, children, and adolescents. The
      content of injury-prevention counseling varies for infants, preschool-aged
      children, school-aged children, and adolescents. This report provides guidance on
      the content of unintentional injury-prevention counseling for each of those age
      groups.

PMID- 17200290
TI  - Recommended immunization schedules for children and adolescents--United States,
      2007.

PMID- 17200291
TI  - Intratracheal sildenafil in the newborn with pulmonary hypertension.

PMID- 17200292
TI  - The need to assess benefits and not just risks of 100% oxygen for newborn
      resuscitation.

PMID- 17200293
TI  - Give Synagis via home health.

PMID- 17200294
TI  - Predictive model for Lyme meningitis: a reply.

PMID- 17200296
TI  - The research failed, but the patients are doing well.

PMID- 17200295
TI  - Treated hypotension in extremely low birth weight infants.

PMID- 17200297
TI  - Trends in asthma prevalence and recommended number of childhood immunizations are
      not parallel.

PMID- 17200298
TI  - The economic burden of all-terrain vehicle-related pediatric deaths in the United
      States.

PMID- 17200299
TI  - Further efforts to reduce the incidence of neural tube defects.

PMID- 17200300
TI  - How much sucrose is too much sucrose?

PMID- 17200301
TI  - Distinguishing between cooperative and unimodal downhill protein folding.
AB  - Conventional cooperative protein folding invokes discrete ensembles of native and
      denatured state structures in separate free-energy wells. Unimodal noncooperative
      ("downhill") folding, however, proposes an ensemble of states occupying a single
      free-energy well for proteins folding at >/=4 x 10(4) s(-1) at 298 K. It is
      difficult to falsify unimodal mechanisms for such fast folding proteins by
      standard equilibrium experiments because both cooperative and unimodal mechanisms
      can present the same time-averaged structural, spectroscopic, and thermodynamic
      properties when the time scale used for observation is longer than for
      equilibration. However, kinetics can provide the necessary evidence. Chevron
      plots with strongly sloping linear refolding arms are very difficult to explain
      by downhill folding and are a signature for cooperative folding via a transition
      state ensemble. The folding kinetics of the peripheral subunit binding domain POB
      and its mutants fit to strongly sloping chevrons at observed rate constants of >6
      x 10(4) s(-1) in denaturant solution, extrapolating to 2 x 10(5) s(-1) in water.
      Protein A, which folds at 10(5) s(-1) at 298 K, also has a well-defined chevron.
      Single-molecule fluorescence energy transfer experiments on labeled Protein A in
      the presence of denaturant demonstrated directly bimodal distributions of native
      and denatured states.

PMID- 17200302
TI  - Ab and T cell epitopes of influenza A virus, knowledge and opportunities.
AB  - The Immune Epitope Database and Analysis Resources (IEDB) (www.immuneepitope.org)
      was recently developed to capture epitope related data. IEDB also hosts various
      bioinformatics tools that can be used to identify novel epitopes as well as to
      analyze and visualize existing epitope data. Herein, a comprehensive analysis was
      undertaken (i) to compile and inventory existing knowledge regarding influenza A
      epitopes and (ii) to determine possible cross-reactivities of identified epitopes
      among avian H5N1 and human influenza strains. At present, IEDB contains >600
      different epitopes derived from 58 different strains and 10 influenza A proteins.
      By using the IEDB analysis resources, conservancy analyses were performed, and
      several conserved and possibly cross-reactive epitopes were identified.
      Significant gaps in the current knowledge were also revealed, including paucity
      of Ab epitopes in comparison with T cell epitopes, limited number of epitopes
      reported for avian influenza strains/subtypes, and limited number of epitopes
      reported from proteins other than hemagglutinin and nucleoprotein. This analysis
      provides a resource for researchers to access existing influenza epitope data. At
      the same time, the analysis illustrates gaps in our collective knowledge that
      should inspire directions for further study of immunity against the influenza A
      virus.

PMID- 17200303
TI  - Nonoperative treatment compared with plate fixation of displaced midshaft
      clavicular fractures. A multicenter, randomized clinical trial.
AB  - BACKGROUND: Recent studies have shown a high prevalence of symptomatic malunion
      and nonunion after nonoperative treatment of displaced midshaft clavicular
      fractures. We sought to compare patient-oriented outcome and complication rates
      following nonoperative treatment and those after plate fixation of displaced
      midshaft clavicular fractures. METHODS: In a multicenter, prospective clinical
      trial, 132 patients with a displaced midshaft fracture of the clavicle were
      randomized (by sealed envelope) to either operative treatment with plate fixation
      (sixty-seven patients) or nonoperative treatment with a sling (sixty-five
      patients). Outcome analysis included standard clinical follow-up and the Constant
      shoulder score, the Disability of the Arm, Shoulder and Hand (DASH) score, and
      plain radiographs. One hundred and eleven patients (sixty-two managed operatively
      and forty-nine managed nonoperatively) completed one year of follow-up. There
      were no differences between the two groups with respect to patient demographics,
      mechanism of injury, associated injuries, Injury Severity Score, or fracture
      pattern. RESULTS: Constant shoulder scores and DASH scores were significantly
      improved in the operative fixation group at all time-points (p = 0.001 and p <
      0.01, respectively). The mean time to radiographic union was 28.4 weeks in the
      non-operative group compared with 16.4 weeks in the operative group (p = 0.001).
      There were two nonunions in the operative group compared with seven in the
      nonoperative group (p = 0.042). Symptomatic malunion developed in nine patients
      in the nonoperative group and in none in the operative group (p = 0.001). Most
      complications in the operative group were hardware-related (five patients had
      local irritation and/or prominence of the hardware, three had a wound infection,
      and one had mechanical failure). At one year after the injury, the patients in
      the operative group were more likely to be satisfied with the appearance of the
      shoulder (p = 0.001) and with the shoulder in general (p = 0.002) than were those
      in the nonoperative group. CONCLUSIONS: Operative fixation of a displaced
      fracture of the clavicular shaft results in improved functional outcome and a
      lower rate of malunion and nonunion compared with nonoperative treatment at one
      year of follow-up. Hardware removal remains the most common reason for repeat
      intervention in the operative group. This study supports primary plate fixation
      of completely displaced midshaft clavicular fractures in active adult patients.

PMID- 17200304
TI  - Influence of preoperative functional status on outcome after total hip
      arthroplasty.
AB  - BACKGROUND: International registries with large, heterogeneous patient
      populations provide excellent research opportunities for studying factors that
      influence treatment outcomes after total hip arthroplasty. In the present study,
      we used a European multinational database to investigate whether there is an
      association between three functional variables (preoperative pain, mobility, and
      motion) and functional outcome. METHODS: We performed a retrospective cohort
      study on preoperative and follow-up clinical data that were prospectively entered
      into the International Documentation and Evaluation System European hip registry
      between 1967 and 2002. The inclusion criteria for this study were an age of more
      than twenty years, an underlying diagnosis of osteoarthritis, and a Charnley
      class-A functional designation at the time of surgery. A total of 12,925 patients
      (13,766 total hip arthroplasties) who met these criteria were entered into the
      analysis. Three functional variables (pain, mobility, and motion) that were
      assessed preoperatively were evaluated postoperatively at various follow-up
      examinations for a maximum of ten years. RESULTS: Six thousand four hundred and
      one patients could walk longer than ten minutes preoperatively; of these, 57.1%
      had a walking capacity of more than sixty minutes at the time of the most recent
      follow-up. In comparison, 6896 patients had a preoperative walking capacity of
      less than ten minutes and only 38.9% of these patients could walk more than sixty
      minutes at the time of the most recent follow-up. The difference was significant
      (p < 0.01). Similarly, 10,375 patients had a preoperative hip flexion range of
      >70 degrees ; of these, 74.7% had a flexion range of >90 degrees at the time of
      the most recent follow-up. In comparison, 2793 patients had a preoperative hip
      flexion range of <70 degrees and only 62.6% of these patients had a flexion range
      of >90 degrees at the time of the most recent follow-up. The difference was also
      significant (p < 0.01). Lasting, complete, or almost complete pain relief was
      achieved by >80% of the patients following total hip arthroplasty regardless of
      their preoperative categorization of pain. CONCLUSIONS: Patients with poor
      preoperative walking capacity and hip flexion are less likely to achieve an
      optimal outcome with regard to walking and motion. In contrast, there is no
      correlation between the preoperative pain level and pain alleviation, which is
      generally good and long-lasting after total hip arthroplasty.

PMID- 17200305
TI  - Long-term results of surgery for brachial plexus birth palsy.
AB  - BACKGROUND: The long-term results of surgical treatment of brachial plexus birth
      palsy have not been reported. We present the findings of a nationwide study, with
      a minimum five-year follow-up, of the outcomes of surgery for brachial plexus
      birth palsy in Finland. METHODS: Of 1,717,057 newborns, 1706 with brachial plexus
      birth palsy requiring hospital treatment were registered in Finland between 1971
      and 1997. Of these patients, 124 (7.3%) underwent surgery on the brachial plexus
      at a mean age of 2.8 months (range, 0.4 to 13.2 months). The most commonly
      performed surgical procedure was direct neurorrhaphy after neuroma resection. One
      hundred and twelve patients (90%) returned for a clinical and radiographic follow
      up examination after a mean of 13.3 years. Activities of daily living were
      recorded on a questionnaire, and the affected limb was assessed with use of joint
      specific functional measures. RESULTS: Two-thirds (63%) of the patients were
      satisfied with the functional outcome, although one-third of all patients needed
      help in activities of daily living. One-third of the patients, including all nine
      with a clavicular nonunion from the surgical approach, experienced pain in the
      affected limb. All except four patients used the hand of the unaffected limb as
      the dominant hand. Shoulder function was moderate, with a mean Mallet score of
      3.0. Both elbow and hand function were good, with a mean score on the Gilbert
      elbow scale of 3 and a mean Raimondi hand score of 4. Incongruence of the
      glenohumeral joint was noted in sixteen (16%) of the ninety-nine patients in whom
      it was assessed, and incongruence of the radiohumeral joint was noted in twenty
      one (21%). The extent of the brachial plexus injury was found to be strongly
      associated with the final shoulder, elbow, and hand function in a multivariate
      analysis. CONCLUSIONS: Following surgical treatment of brachial plexus birth
      palsy, substantial numbers of the patients continued to need help performing
      activities of daily living and had pain in the affected limb, with the pain due
      to a clavicular nonunion in one-fourth of the patients. The strongest prognostic
      factor predicting outcome appears to be the extent of the primary plexus injury.

PMID- 17200306
TI  - Total joint arthroplasty: When do fatal or near-fatal complications occur?
AB  - BACKGROUND: With the recent trend toward minimally invasive total joint
      arthroplasty and the increased emphasis on faster recovery and shorter hospital
      stays, it has become increasingly important to recognize the timing and severity
      of the various complications associated with elective total joint arthroplasty to
      ensure that early patient discharge is a safe practice. METHODS: We evaluated the
      systemic and local complications associated with primary unilateral lower
      extremity arthroplasties performed during one year in 1636 patients. A total of
      966 patients had a primary total hip arthroplasty, and 670 had a primary total
      knee arthroplasty. All complications that occurred in the hospital and for six
      weeks following the index surgery were recorded. The circumstances leading to the
      complications and the details of the therapeutic intervention for each
      complication were recorded. Analyses were performed to predict the factors that
      predispose patients to serious complications. RESULTS: One patient (0.06%) in the
      cohort died during the hospital stay. There were a total of 104 major (life
      threatening) complications, including cardiac arrest (one), tachyarrhythmia
      (thirty-three), pulmonary edema or congestive heart failure (ten), myocardial
      infarction (six), hypotensive crisis (four), pulmonary embolus (twenty-five),
      acute renal failure (fourteen), stroke (six), bowel obstruction or perforation
      (three), and pneumothorax (one). There were seventeen major local complications.
      Ninety-four (90%) of the major complications occurred within four days after the
      index surgery. Although older age, increased body mass, and preexistent
      comorbidities were important predisposing factors for serious medical
      complications, 58% of the patients who had life-threatening complications develop
      had no identifiable predisposing factors. CONCLUSIONS: This study demonstrated
      that most of the complications of lower-extremity total joint replacement occur
      within the time-frame of the typical hospital stay. Given the serious nature of
      some of these complications and the inability to identify many of the patients
      who may be at risk, we caution against early discharge of patients from the
      hospital after elective total joint arthroplasty in the lower extremity.

PMID- 17200307
TI  - Factors associated with prolonged wound drainage after primary total hip and knee
      arthroplasty.
AB  - BACKGROUND: Prolonged wound drainage following total hip or total knee
      arthroplasty has been associated with an increased risk of postoperative
      morbidity. The purpose of this study was to determine the pharmacologic,
      surgical, and patient-specific factors that are associated with prolonged wound
      drainage and the relationship of this complication to the length of hospital stay
      and the rate of wound infections. METHODS: We conducted a retrospective
      observational study of 1211 primary total hip arthroplasties and 1226 primary
      total knee arthroplasties. Prospectively collected data included body mass index,
      intraoperative blood loss, surgical time, type of prophylaxis against deep venous
      thrombosis, and length of hospital stay. The association of these factors with
      the duration of postoperative wound drainage was analyzed. An acute infection
      developed after fifteen primary total hip arthroplasties and ten primary total
      knee arthroplasties. The patients with an acute postoperative infection were
      compared with their uninfected counterparts, and an odds ratio was determined to
      estimate the risk of prolonged wound drainage resulting in a wound infection.
      RESULTS: Morbid obesity was strongly associated with prolonged wound drainage in
      the total hip arthroplasty group (p = 0.001) but not in the total knee
      arthroplasty group (p = 0.590). An increased volume of drain output was an
      independent risk factor for prolonged wound drainage in both groups. Patients who
      received low-molecular-weight heparin for prophylaxis against deep venous
      thrombosis had a longer time until the postoperative wound was dry than did those
      treated with aspirin and mechanical foot compression or those who received
      Coumadin (warfarin); this difference was significant on the fifth postoperative
      day (p = 0.003) but not by the eighth postoperative day. Prolonged wound drainage
      resulted in a significantly longer hospital stay in both groups (p < 0.001). Each
      day of prolonged wound drainage increased the risk of wound infection by 42%
      following a total hip arthroplasty and by 29% following a total knee
      arthroplasty. CONCLUSIONS: Morbid obesity, the use of low-molecular-weight
      heparin, and a higher drain output were associated with a prolonged time until
      the postoperative wound was dry following a primary total hip arthroplasty,
      whereas a higher drain output was the only risk factor associated with prolonged
      drainage following a primary total knee arthroplasty. Prolonged drainage was
      associated with a higher rate of infection following a primary total hip
      arthroplasty, whereas obesity was the only identified independent risk factor for
      postoperative infection following a primary total knee arthroplasty.

PMID- 17200308
TI  - Diagnosis of femoral neck fractures in patients with a femoral shaft fracture.
      Improvement with a standard protocol.
AB  - BACKGROUND: An ipsilateral fracture of the femoral neck is seen in association
      with 1% to 9% of femoral shaft fractures, and 20% to 50% of these injuries are
      missed initially. Recognition of an associated femoral neck fracture prior to
      stabilization of the femoral shaft fracture is imperative to avoid or minimize
      complications of displacement and osteonecrosis. METHODS: A protocol to look for
      a femoral neck fracture in all patients with a femoral shaft fracture was
      instituted at a single level-I trauma center. This protocol consisted of a
      dedicated anteroposterior internal rotation plain radiograph, a fine (2-mm) cut
      computed tomographic scan through the femoral neck, and an intraoperative
      fluoroscopic lateral radiograph prior to fixation as well as postoperative
      anteroposterior and lateral radiographs of the hip in the operating room prior to
      awakening the patient. A chi-square analysis comparing pre-protocol and post
      protocol fracture prevalences was used to assess the relative risk of missing an
      associated femoral neck fracture. RESULTS: Two hundred and sixty-eight
      consecutive patients with a femoral shaft fracture formed the basis of the study
      group. Of 254 who were followed for at least two months, sixteen were identified
      as having an associated ipsilateral femoral neck fracture with use of the
      protocol. Thirteen associated femoral neck fractures were identified before the
      patient entered the operating room for definitive fixation, and twelve of them
      were identified with the fine-cut computed tomographic scan. One fracture was
      identified intraoperatively. There was one iatrogenic fracture and one delayed
      diagnosis of a femoral neck fracture. With this protocol, we reduced the delay in
      diagnosis by 91% as compared with our experience in the year prior to the
      initiation of the protocol. CONCLUSIONS: In the presence of a femoral shaft
      fracture, evaluation of the femoral neck with fine-cut computed tomography and
      dedicated internal rotation hip radiographs significantly improves the ability to
      diagnose an associated femoral neck fracture.

PMID- 17200309
TI  - The proximal origin of the hamstrings and surrounding anatomy encountered during
      repair. A cadaveric study.
AB  - BACKGROUND: Avulsion of the proximal origin of the hamstrings has become a more
      frequently recognized athletic injury. Most orthopaedic surgeons rarely operate
      in this anatomic area. The purpose of the present study was to define the anatomy
      of the proximal origin of the hamstrings and its relationship to neurovascular
      and muscular structures encountered during a repair of a complete avulsion.
      METHODS: Fourteen fresh-frozen hip-to-foot human cadaveric specimens were
      dissected in the prone position. The proximal origin of the hamstrings and its
      relationship to the surrounding neurologic and muscular structures were
      documented and measured with use of digital calipers. RESULTS: Six of the
      fourteen specimens were from female donors. The average age of the donors at the
      time of death was 68 +/- 13 years. The average height of the donors was 66 +/-
      3.5 in (167 +/- 8.9 cm), and the average weight was 142 +/- 39 lb (64 +/- 17.7
      kg). The semitendinosus and biceps femoris have a common tendinous site of origin
      on the ischium. A number of measurements were obtained. The musculotendinous
      junctions of the semitendinosus and biceps femoris separated at an average of 9.9
      +/- 1.5 cm from the most proximal origin site on the ischium. The average
      distance from the proximal border of the semitendinosus/biceps femoris origin to
      the inferior border of the gluteus maximus was 6.3 +/- 1.3 cm. At the lateral
      border of the ischium, the average distance from the inferior gluteal nerve and
      artery to the inferior border of the gluteus maximus was 5.0 +/- 0.8 cm. The
      sciatic nerve was an average of 1.2 +/- 0.2 cm from the most lateral aspect of
      the ischial tuberosity. The site of origin of the semitendinosus/biceps femoris
      was oval, with average measurements of 2.7 +/- 0.5 cm from proximal to distal and
      of 1.8 +/- 0.2 cm from medial to lateral. The site of origin of the
      semimembranosus was crescent-shaped, with average measurements of 3.1 +/- 0.3 cm
      from proximal to distal and of 1.1 +/- 0.5 cm from medial to lateral.
      CONCLUSIONS: The semitendinosus and biceps femoris have a common tendon of origin
      on the ischium, and the semimembranosus originates just laterally. The proximal
      origin of the hamstrings has intimate relationships with the inferior gluteal
      nerve and artery and the sciatic nerve, which may be at risk during surgical
      dissection and retraction.

PMID- 17200310
TI  - Compaction bone-grafting in prosthetic shoulder arthroplasty.
AB  - BACKGROUND: Compaction bone-grafting has been suggested as a means of improving
      the stability of the humeral component in shoulder arthroplasty, but the clinical
      and radiographic results of the procedure have not been reported in the
      literature, to our knowledge. To address this deficit, we report on a series of
      shoulder arthroplasties performed with compaction bone-grafting to secure humeral
      component fixation. These prostheses were implanted in shoulders demonstrating a
      suboptimal interference fit of the humeral component. METHODS: Fifty-eight
      shoulders in fifty-three patients were treated with prosthetic shoulder
      arthroplasty that included compaction bone-grafting. Clinical assessments were
      performed at regular intervals with use of visual analog scales for pain,
      shoulder comfort and function, and overall quality of life, and with use of
      patient self-assessments including the American Shoulder and Elbow Surgeons Score
      and the validated Simple Shoulder Test. A detailed radiographic analysis was
      performed by three raters to determine whether radiolucent lines were present
      immediately postoperatively and at a later follow-up interval. The humeral tilt
      angle was determined by measuring the angle between the humeral axis and the
      component. Subsidence was also evaluated. The mean of the raters' measurements
      was used in the analysis. RESULTS: The mean duration of follow-up was sixty-nine
      months (range, twenty-six to 148 months). No loose stems were observed, and no
      humeral component was revised. At the time of follow-up, there was significant
      improvement in the Simple Shoulder Test scores and all visual analog scores (p <
      0.0001 in each instance). Thirty-four stems had no radiolucent line at the time
      of follow-up, and the mean maximum thickness of the lucent lines was 0.21 mm in
      the entire group of fifty-eight shoulders. Most lucent lines occurred near the
      distal stem tip. The mean tilt of the valgus and varus humeral components was 2.2
      degrees and 2.6 degrees , respectively, on the immediate postoperative
      radiographs. No humeral component shifted from varus to valgus or vice versa. The
      duration of follow-up was not correlated with the maximum thickness of the
      humeral component lucency, and the presence or absence of a prosthetic glenoid
      was also unrelated to the maximum thickness of the lucency. CONCLUSIONS:
      Compaction bone-grafting in shoulder arthroplasty can yield stable and durable
      fixation of the humeral component, as seen clinically and radiographically,
      without use of cement. Our findings provide evidence that compaction bone
      grafting in shoulder arthroplasty is an option to ensure intermediate-term
      fixation (at a mean of five years) of humeral components that have a suboptimal
      fit.

PMID- 17200311
TI  - Internal oblique radiographs for diagnosis of nondisplaced or minimally displaced
      lateral condylar fractures of the humerus in children.
AB  - BACKGROUND: Several radiographic criteria based on only standard anteroposterior
      and lateral radiographs have been suggested for predicting the stability of
      lateral condylar fractures of the humerus in children. Despite adherence to these
      guidelines, further displacement often occurs after the initial diagnosis and
      stability assessment. The purpose of this study was to define the usefulness of
      an internal oblique radiograph in the assessment of these fractures. METHODS: We
      prospectively studied fifty-four lateral humeral condylar fractures in fifty-four
      children seen between March 2002 and December 2004 to determine the efficacy of
      internal oblique radiographs in gauging the amount of displacement and the
      fracture pattern. Plain anteroposterior, lateral, internal oblique, and external
      oblique radiographs were initially made for all fifty-four patients, and three
      dimensional computed tomography scans were performed for seven patients. RESULTS:
      A large percentage (70%) of the fractures were seen to have different amounts of
      displacement on the anteroposterior and internal oblique radiographs, and a large
      percentage (75%) were seen to have different fracture patterns, according to the
      criteria suggested by Finnbogason et al., on the two views. The internal oblique
      radiograph was more accurate for demonstrating the fracture gap (thirty cases
      were seen to have more displacement on that view) and for demonstrating the
      fracture pattern (twenty cases were seen to have more instability on the internal
      oblique view). We also confirmed the direction of the fracture line and the
      location of the fragment more accurately with three-dimensional computed
      tomography. CONCLUSIONS: It is not optimal to evaluate the amount of displacement
      and the stability of a lateral condylar fracture of the humerus in children on
      the basis of just anteroposterior and lateral elbow radiographs. Classifications
      should be based on the greatest displacement seen on at least three radiographic
      views, especially the internal oblique view.

PMID- 17200312
TI  - Maturity assessment and curve progression in girls with idiopathic scoliosis.
AB  - BACKGROUND: Scoliosis progression during adolescence is closely related to
      patient maturity. Maturity has various indicators, including chronological age,
      height and weight changes, and skeletal and sexual maturation. It is not certain
      which of these indicators correlates most strongly with scoliosis progression.
      The purpose of the present study was to evaluate various maturity measurements
      and how they relate to scoliosis progression. METHODS: Physically immature girls
      with idiopathic scoliosis were evaluated every six months through their growth
      spurt with serial spinal radiographs; hand skeletal ages; Oxford pelvic scores;
      Risser sign determinations; height; weight; sexual staging; and serologic studies
      of the levels of selected growth factors, estradiol, bone-specific alkaline
      phosphatase, and osteocalcin. These measurements were then correlated with the
      curve-acceleration phase. RESULTS: The period and pattern of curve acceleration
      began during Risser stage 0 for all patients. Skeletal maturation scores derived
      with the use of the Tanner-Whitehouse-III RUS method, particularly those for the
      metacarpals and phalanges, were superior to all other indicators of maturity.
      Regression of the scores provided good estimates of maturity relative to the
      period of curve progression (Pearson r = 0.93). The initiation of this period
      occurred simultaneously with digital changes from Tanner-Whitehouse-III stage F
      to G. At this stage, curves also separated into rapid, moderate, and low
      acceleration patterns, with specific curve types in the rapid and moderate
      acceleration groups. The low-acceleration group was not confined to a specific
      curve type. CONCLUSIONS: The curve-acceleration phase separates curves into
      various types of curve progression. The Tanner-Whitehouse-III RUS scores are
      highly correlated with timing relative to the curve-acceleration phase and
      provide better maturity determination and prognosis determination during
      adolescence than the other parameters tested. Accurate skeletal maturity
      determination should be used as the primary maturity measurement in girls with
      idiopathic scoliosis.

PMID- 17200313
TI  - Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a
      rabbit achilles tendon model.
AB  - BACKGROUND: A repaired tendon needs to be protected for weeks until it has
      accrued enough strength to handle physiological loads. Tissue-engineering
      techniques have shown promise in the treatment of tendon and ligament defects.
      The present study tested the hypothesis that bone marrow-derived mesenchymal stem
      cells can accelerate tendon-healing after primary repair of a tendon injury in a
      rabbit model. METHODS: Fifty-seven New Zealand White rabbits were used as the
      experimental animals, and seven others were used as the source of bone marrow
      derived mesenchymal stem cells. The injury model was a sharp complete transection
      through the midsubstance of the Achilles tendon. The transected tendon was
      immediately repaired with use of a modified Kessler suture and a running
      epitendinous suture. Both limbs were used, and each side was randomized to
      receive either bone marrow-derived mesenchymal stem cells in a fibrin carrier or
      fibrin carrier alone (control). Postoperatively, the rabbits were not
      immobilized. Specimens were harvested at one, three, six, and twelve weeks for
      analysis, which included evaluation of gross morphology (sixty-two specimens),
      cell tracing (twelve specimens), histological assessment (forty specimens),
      immunohistochemistry studies (thirty specimens), morphometric analysis (forty
      specimens), and mechanical testing (sixty-two specimens). RESULTS: There were no
      differences between the two groups with regard to the gross morphology of the
      tendons. The fibrin had degraded by three weeks. Cell tracing showed that labeled
      bone marrow-derived mesenchymal stem cells remained viable and present in the
      intratendinous region for at least six weeks, becoming more diffuse at later time
      periods. At three weeks, collagen fibers appeared more organized and there were
      better morphometric nuclear parameters in the treatment group (p < 0.05). At six
      and twelve weeks, there were no differences between the groups with regard to
      morphometric nuclear parameters. Biomechanical testing showed improved modulus in
      the treatment group as compared with the control group at three weeks (p < 0.05)
      but not at subsequent time-periods. CONCLUSIONS: Intratendinous cell therapy with
      bone marrow-derived mesenchymal stem cells following primary tendon repair can
      improve histological and biomechanical parameters in the early stages of tendon
      healing.

PMID- 17200314
TI  - Prevalence of heterotopic ossification following total disc replacement. A
      prospective, randomized study of two hundred and seventy-six patients.
AB  - BACKGROUND: Despite reports of good clinical outcomes in patients treated with
      lumbar and cervical disc replacements, varying degrees of heterotopic bone have
      been observed around these devices. The purposes of the present study were to
      determine the prevalence of heterotopic ossification following lumbar disc
      replacement and to investigate whether heterotopic ossification results in loss
      of motion or negatively affects clinical outcome. METHODS: All preoperative and
      postoperative radiographs from a completed prospective, randomized, United States
      Food and Drug Administration-regulated trial comparing replacement with the
      CHARITE Artificial Disc with anterior interbody arthrodesis were analyzed. In
      each of 276 patients treated with disc replacement, heterotopic ossification was
      categorized with use of a validated 5-point radiographic classification system
      both preoperatively and at all protocol-specified follow-up intervals to two
      years. The range of motion on flexion and extension radiographs made
      preoperatively was compared with that on radiographs made two years
      postoperatively, and the motion was correlated with the presence or absence of
      heterotopic ossification. Similarly, validated clinical outcome measures were
      correlated with the presence or absence of heterotopic ossification at two years.
      RESULTS: The prevalence of heterotopic ossification in the 276 consecutive
      patients treated with lumbar disc replacement with the CHARITE Artificial Disc
      was 4.3%. There were four cases of Class-I heterotopic ossification and eight
      cases of Class-II heterotopic ossification. In five of the twelve patients,
      heterotopic bone was visible as early as six weeks postoperatively, and eleven of
      the twelve patients had evidence of heterotopic ossification by three months
      postoperatively. The postoperative range of motion exceeded the preoperative
      range in all of the patients with heterotopic ossification. With the numbers
      available, no difference in either the range of motion or the clinical outcome at
      twenty-four months postoperatively was found between the patients who had and
      those who did not have heterotopic ossification. CONCLUSIONS: Heterotopic
      ossification is infrequent in patients treated with the CHARITE Artificial Disc,
      and it does not impact the range of motion or clinical outcome.

PMID- 17200315
TI  - Press-fit condylar design total knee arthroplasty. Fourteen to seventeen-year
      follow-up.
AB  - BACKGROUND: The Press-Fit Condylar total knee arthroplasty implant design has
      been used by many orthopaedic surgeons over the last twenty years. The design has
      survived with relatively minor modifications and remains a popular implant system
      today. The present study represents the fourteen to seventeen-year results for
      our patients who were described in our previous report on the eight to ten-year
      results. METHODS: The senior author performed 160 consecutive total knee
      arthroplasties with use of the Press-Fit Condylar cruciate-retaining device in
      134 patients between 1986 and 1989. The mean age of the patients at the time of
      the index procedure was 70.5 years. Follow-up data were available for sixty-three
      of sixty-four surviving knees. Surviving patients were followed for a mean of
      15.8 years. The knees were evaluated on the basis of Knee Society function and
      clinical scores, radiographs, and survivorship analysis. RESULTS: The mean Knee
      Society function score was 65, and the mean clinical score was 89. The overall
      survival rate of the knee was 91.5% with revision for any reason as the end point
      and 97.2% with aseptic loosening as the end point. The rate of revision of the
      tibial insert because of wear-related aseptic loosening was 2.5%. We found no
      relationship between revision and the shelf life or method of sterilization of
      the polyethylene insert. Radiolucent lines were present in 62% (twenty-one) of
      thirty-four knees; all radiolucent lines were nonprogressive. None of the
      implants were loose according to the criteria of the Knee Society. CONCLUSIONS:
      This long-term analysis indicates that the Press-Fit Condylar total knee implant
      is a successful implant system with excellent longevity.

PMID- 17200316
TI  - Alendronate improves screw fixation in osteoporotic bone.
AB  - BACKGROUND: Animal studies have demonstrated the efficacy of the use of
      bisphosphonates to enhance screw fixation in bone. In this prospective,
      randomized study of pertrochanteric fractures treated with external fixation, we
      tested whether systemic administration of bisphosphonates would improve the
      fixation of hydroxyapatite-coated screws implanted in osteoporotic bone. METHODS:
      Sixteen consecutive patients with a pertrochanteric fracture were selected.
      Inclusion criteria were female gender, an age of at least sixty-five years, and a
      bone mineral density T-score of less than -2.5 standard deviations. Exclusion
      criteria included bisphosphonate treatment during the two-year period prior to
      the fracture. Fractures were fixed with a pertrochanteric fixator and four
      hydroxyapatite-coated pins. Two pins were implanted in the femoral head (pin
      positions 1 and 2), and two were placed in the femoral diaphysis (pin positions 3
      and 4). The patients were randomized either to therapy with alendronate for a
      three-month postoperative period (Group A) or to no therapy (Group B). The Group
      A patients received an oral dose of 70 mg of alendronate per week. The fixators
      were removed after three months. RESULTS: All of the fractures healed, and no
      loss of reduction, nonunion, or delayed union was observed. The combined mean
      extraction torque (and standard deviation) of the pins implanted at positions 1
      and 2 (cancellous bone) was 2558 +/- 1103 N/mm in Group A and 1171 +/- 480 N/mm
      in Group B (p < 0.0005). The combined mean extraction torque of the pins
      implanted at positions 3 and 4 (cortical bone) was 4327 +/- 1720 N/mm in Group A
      and 4075 +/- 1022 N/mm in Group B. CONCLUSIONS: These data show that weekly
      systemic administration of alendronate improves pin fixation in cancellous bone
      in elderly female patients with osteoporosis. We observed a twofold increase in
      extraction torque with the pins implanted in cancellous bone. These results
      support the use of alendronate in the treatment of osteoporotic pertrochanteric
      fractures to improve screw fixation in the femoral head.

PMID- 17200317
TI  - Epiphysiodesis with infusion of stromal cell-derived factor-1 in rabbit growth
      plates.
AB  - BACKGROUND: The mechanism of physeal closure is poorly understood, although both
      mechanical and biological factors may play a role in the process. In this study,
      we evaluated the effect of the application of a chemokine stromal cell-derived
      factor-1 (SDF-1) to rabbit physes in vivo with regard to growth inhibition.
      METHODS: A continuous infusion system consisting of a fenestrated catheter and an
      osmotic pump were implanted into the right proximal tibial physis of twenty six
      week-old New Zealand White rabbits. Ten of the pumps were loaded with human
      recombinant SDF-1alpha, and ten were loaded with phosphate-buffered saline
      solution (sham treatment). The left leg was used as the uninvolved control. The
      growth of the tibiae was followed radiographically for eight weeks, and
      histologic analysis was performed for both the SDF-1-treated rabbits and the sham
      treated rabbits at two, four, and eight-week time-points. RESULTS: Radiographic
      evaluation showed a significant growth inhibition in the SDF-1alpha-treated
      physes (4.5 +/- 3.0 mm; p = 0.007) compared with the sham-treated physes after
      eight weeks. No difference was noted when the sham-treated leg was compared with
      the contralateral, control leg (0.2 +/- 2.9 mm; p = 0.465). Histologic evaluation
      showed marked physeal disorganization, narrowing, and proteoglycan loss and a
      significant decrease in physeal height (p < 0.0001) for the SDF-1-treated group.
      Reversible growth slowing was noted in the uninvolved, control leg of the SDF-1
      treated group at six weeks, with resolution of the difference by eight weeks.
      CONCLUSIONS: SDF-1 may be used to induce physeal closure through a targeted
      infusion system. However, transient systemic effects of SDF-1 may exist and must
      be evaluated further prior to its clinical use for epiphysiodesis.

PMID- 17200318
TI  - Selective and nonselective cyclooxygenase-2 inhibitors and experimental fracture
      healing. Reversibility of effects after short-term treatment.
AB  - BACKGROUND: Cyclooxygenase-2-specific anti-inflammatory drugs (coxibs) and
      nonspecific nonsteroidal anti-inflammatory drugs have been shown to inhibit
      experimental fracture-healing. The present study tested the hypothesis that these
      effects are reversible after short-term treatment. METHODS: With use of a
      standard model of fracture-healing, identical ED50 dosages of either a
      nonsteroidal anti-inflammatory drug (ketorolac), a coxib (valdecoxib), or vehicle
      (control) were orally administered to rats for either seven or twenty-one days
      and fracture-healing was assessed with biomechanical, histological, and
      biochemical analyses. RESULTS: When healing was assessed at twenty-one days, the
      seven-day treatment produced only a trend for a higher rate of nonunion in
      valdecoxib and ketorolac-treated animals as compared with controls. No
      differences were observed at thirty-five days. The twenty-one-day treatment
      produced significantly more nonunions in valdecoxib-treated animals as compared
      with either ketorolac-treated or control animals (p < 0.05), but these
      differences disappeared by thirty-five days. The dose-specific inhibition of
      these drugs on prostaglandin E2 levels and the reversibility of the effects after
      drug withdrawal were assessed in fracture calluses and showed that ketorolac
      treatment led to twofold to threefold lower levels of prostaglandin E2 than did
      valdecoxib. Withdrawal of either drug after six days led to a twofold rebound in
      these levels by fourteen days. Histological analysis showed delayed remodeling of
      calcified cartilage and reduced bone formation in association with valdecoxib
      treatment. CONCLUSIONS: Cyclooxygenase-2-specific drugs inhibit fracture-healing
      more than nonspecific nonsteroidal anti-inflammatory drugs, and the magnitude of
      the effect is related to the duration of treatment. However, after the
      discontinuation of treatment, prostaglandin E2 levels are gradually restored and
      the regain of strength returns to levels similar to control.

PMID- 17200319
TI  - Total hip arthroplasty with a cemented, polished, collared femoral stem and a
      cementless acetabular component. A follow-up study at a minimum of ten years.
AB  - BACKGROUND: Recent studies have suggested that cemented femoral components with a
      polished surface may provide superior long-term fixation when compared with
      femoral components with a roughened surface. The purpose of this study was to
      evaluate the results of total hip arthroplasty with a cemented femoral component
      with a polished surface finish and compare them with the results of total hip
      arthroplasty performed with a similar design of cemented femoral component with a
      rougher surface finish. METHODS: We retrospectively reviewed a consecutive group
      of 132 patients (149 hips) in whom primary total hip arthroplasty had been
      performed by one surgeon using a cemented collared femoral component with a
      polished (0.1-microm Ra) surface finish and a cementless acetabular component.
      Ninety-eight patients (115 hips) were followed for a minimum of ten years. We
      compared the survivorship of this prosthesis with that of a femoral component of
      similar design but with rougher surfaces (matte or grit-blasted). RESULTS: No
      polished stems were revised because of aseptic loosening or demonstrated
      radiographic evidence of loosening; however, eight hips (5.4%) with a polished
      stem demonstrated osteolysis distal to the greater or lesser tro-chanter. In
      contrast, six stems (2.0%) with a matte surface finish of 0.8-microm Ra were
      revised because of aseptic loosening, and an additional five stems were seen to
      be loose radiographically. Eleven stems (9.2%) with a grit-blasted surface finish
      of 2.1-microm Ra were revised because of aseptic loosening, and an additional
      four stems were seen to be loose radiographically. The difference in the
      prevalence of revision due to aseptic loosening between the group with the 0.1
      microm Ra surface and the group with the 2.1-microm Ra surface was significant (p
      = 0.001), as was the difference between the prevalence of revision due to aseptic
      loosening between the group with the 0.8-microm Ra surface and the group with the
      2.1-microm Ra surface (p = 0.001). No cups were revised because of aseptic
      loosening, and one hip had radiographic signs of acetabular loosening.
      CONCLUSIONS: This study demonstrated excellent durability of a prosthesis
      consisting of a cemented, collared, polished femoral component and a cementless
      acetabular component. While no hips were revised because of aseptic loosening,
      distal femoral osteolysis was observed in eight hips (5.4%), a higher prevalence
      than has been reported by others after similar durations of follow-up of tapered,
      collarless, polished femoral components.

PMID- 17200320
TI  - Safe zone for the placement of medial malleolar screws.
AB  - BACKGROUND: Hardware placement for fracture fixation can put soft-tissue
      structures at risk for injury or abutment. The prominence of the hardware is a
      frequent cause of pain after the fixation of ankle fractures. This study was
      designed to assess the risk of injury or abutment of the posterior tibial tendon
      with the placement of medial malleolar screws. METHODS: Ten unmatched cadaveric
      limbs that had been disarticulated at the knee were used, and the medial
      malleolus was exposed by dissection of the skin. With use of fluoroscopy and
      direct visualization of the deep fascia, three Kirschner wires were placed
      through the tip of the medial malleolus and directed parallel to the medial
      articular surface. The first wire was placed in the center of the anterior
      colliculus. Two additional wires were placed parallel and posterior to the
      initial wire at 5-mm intervals. The wires were overdrilled, and 4.0-mm screws
      were inserted over the Kirschner wires. The specimens were dissected to inspect
      for trauma and the proximity of the screws to the posterior tibial tendon. The
      medial malleolus was divided into three zones on the basis of anatomic landmarks.
      Zone 1 is the anterior colliculus; Zone 2, the intercollicular groove; and Zone
      3, the posterior colliculus. RESULTS: Screws placed in Zone 1 (the anterior
      colliculus) did not contact the posterior tibial tendon in any specimens. Screws
      placed in Zone 2 (the intercollicular groove) were, on the average, 2 mm from the
      posterior tibial tendon. Screws placed in Zone 3 (the posterior colliculus)
      resulted in tendon abutment in all ten specimens and in tendon injury in five of
      the ten specimens. CONCLUSIONS: Screws inserted posterior to the anterior
      colliculus place the posterior tibial tendon at significant risk for injury or
      abutment.

PMID- 17200321
TI  - Platelet-rich plasma inhibits demineralized bone matrix-induced bone formation in
      nude mice.
AB  - BACKGROUND: It is unclear whether platelet-rich plasma is a clinically effective
      adjunct to osteoinductive agents such as demineralized bone matrix. It contains
      platelet-derived growth factor (PDGF), which decreases osteoinduction by human
      demineralized bone matrix in nude-mouse muscle, suggesting that platelet-rich
      plasma may also have a negative impact. This study tested the hypothesis that
      platelet-rich plasma reduces demineralized bone matrix-induced bone formation and
      that this effect varies with donor-dependent differences in platelet-rich plasma
      and demineralized bone matrix. METHODS: Human platelet-rich plasma was prepared
      from blood from six men (average age [and standard error of the mean], 29.2 +/-
      2.4 years). Platelet numbers were determined, and growth factors were quantified
      before and after platelet activation. Human demineralized bone matrix from two
      donors (demineralized bone matrix-1 and demineralized bone matrix-2) was mixed
      with activated platelet-rich plasma and was implanted bilaterally in the
      gastrocnemius muscle in eighty male nude mice (eight implants per variable).
      Fifty-six days after implantation, the hindlimb calf muscles were harvested for
      histological analysis. Osteoinduction was evaluated with use of a qualitative
      score and morphometric measurements of ossicle size, new bone formation, and
      residual demineralized bone matrix. RESULTS: Compared with platelet-poor plasma,
      platelet-rich plasma preparations exhibited a fourfold increase in the platelet
      count, a fifteenfold increase in the amount of transforming growth factor-beta, a
      sixfold increase in the amount of PDGF-BB, a fivefold increase in the amount of
      PDGF-AA, and a twofold increase in the amount of PDGF-AB. Demineralized bone
      matrix-1 was more osteoinductive than demineralized bone matrix-2, as determined
      on the basis of a greater ossicle area. The effect of platelet-rich plasma was
      either neutral or inhibitory depending on the demineralized bone matrix batch.
      When used with demineralized bone matrix-1, platelet-rich plasma did not alter
      the qualitative score or overall ossicle size, but it decreased the new bone
      area. When used with demineralized bone matrix-2, platelet-rich plasma reduced
      the qualitative score, ossicle area, and new bone area and increased the amount
      of residual demineralized bone matrix. The effects on osteoinduction also varied
      with the donor of the platelet-rich plasma. CONCLUSIONS: Platelet-rich plasma
      decreased the osteoinductivity of demineralized bone matrix implanted in
      immunocom-promised mice, and the activities of both demineralized bone matrix and
      platelet-rich plasma were donor-dependent.

PMID- 17200322
TI  - Inflammatory and immunological responses to hyaluronan preparations. Study of a
      murine biocompatibility model.
AB  - BACKGROUND: Intra-articular injection of hyaluronan preparations is a popular
      treatment for osteoarthritis of the knee. Recently, clinical reports have
      described acute inflammatory reactions in joints following these injections. The
      purpose of this study was to use a murine pouch model to study the local
      inflammatory and possibly immunological effects of three commercially available
      hyaluronan-derived products. METHODS: Each of three different hyaluronan products
      (Synvisc, Hyalgan, and Supartz) was injected into air pouches established in
      groups of BALB/c mice. A positive control group (with particle-induced
      inflammation) and a negative control group (injected with saline solution) were
      also included. After fourteen days, the mice were killed and the air pouches were
      explanted and prepared for histological evaluation of the local inflammatory
      reaction. The antibody response was measured with use of ELISA (enzyme-linked
      immunosorbent assay) of serum samples obtained after the mice were killed.
      RESULTS: Histological analysis revealed a significant increase in total membrane
      cellularity (p < 0.001 to p < 0.03) after the use of all hyaluronan preparations.
      The increased cellularity was attributed to an inflammatory cell influx, rather
      than accumulation of fibroblasts, and elevated lymphocyte counts were observed in
      membranes stimulated by Synvisc (hylan G-F 20). The ELISA data revealed an
      antibody response to the Synvisc preparation. This immunological response was
      directed against a non-hyaluronan portion of the product, as indicated by the
      lack of cross-reactivity with the other hyaluronan products. CONCLUSIONS: These
      findings demonstrate that all three hyaluronan preparations, as currently
      manufactured, can cause an inflammatory soft-tissue reaction, but only the non
      hyaluronan portion of the Synvisc product created an immunological response. It
      appears likely that this component may be the target of adverse responses in
      patients.

PMID- 17200323
TI  - Twenty-five-year chondrocyte viability in fresh osteochondral allograft. A case
      report.

PMID- 17200324
TI  - Donor cell survival in a fresh osteochondral allograft at twenty-nine years. A
      case report.

PMID- 17200325
TI  - Odontoid process fracture in children: delayed diagnosis and successful
      conservative management with a halo cast. A report of two cases.

PMID- 17200327
TI  - Symposium integrating evidence-based medicine into clinical practice.

PMID- 17200326
TI  - Exchange nailing of ununited fractures.
AB  - Exchange nailing is most appropriate for a nonunion without substantial bone
      loss. There is no clear consensus regarding the use of exchange nailing in the
      presence of active, purulent infection. The exchange nail should be at least 1 mm
      larger in diameter than the nail being removed, and it has been recommended that
      it be up to 4 mm larger when the nail being removed was greatly undersized. Canal
      reaming should progress until osseous tissue is observed in the reaming flutes.
      Exchange nailing is an excellent choice for aseptic nonunions of noncomminuted
      diaphyseal femoral fractures, with union rates reported to range from 72% to
      100%. On the basis of the available literature, exchange nailing cannot be
      recommended for distal femoral nonunions at this time. Exchange nailing is an
      excellent choice for aseptic nonunions of noncomminuted diaphyseal tibial
      fractures, with union rates reported to range from 76% to 96%. On the basis of
      the available literature, exchange nailing is generally not indicated for humeral
      nonunions.

PMID- 17200328
TI  - Perceptions and competence in evidence-based medicine: Are surgeons getting
      better? A questionnaire survey of members of the Dutch Orthopaedic Association.
AB  - BACKGROUND: The Journal of Bone and Joint Surgery, American Volume (The Journal)
      recently initiated a section called "Evidence-Based Orthopaedics." Furthermore, a
      level-of-evidence rating is now used in The Journal to help readers in clinical
      decision-making. Little is known about whether this recent emphasis has
      influenced surgeons' perceptions about and competence in evidence-based medicine.
      Therefore, we examined perceptions and competence in evidence-based medicine
      among Dutch orthopaedic surgeons. METHODS: Members of the Dutch Orthopaedic
      Association were surveyed to examine their attitudes toward evidence-based
      medicine and their competence in evidence-based medicine. We evaluated
      competences using a newly developed instrument tailored to surgical practice.
      RESULTS: Of the 611 members, 367 surgeons (60%) responded. Orthopaedic surgeons
      welcomed evidence-based medicine. Practical evidence-based medicine resources
      were perceived as the best method to move from opinion-based or experience-based
      to evidence-based practice. Four variables were significantly and positively
      associated with the competence instrument: (1) a younger age, particularly
      between thirty-six and forty-five years (p = 0.007), (2) experience of less than
      ten years (p = 0.032), (3) having a PhD degree (p < 0.001), and (4) working in an
      academic or teaching setting (p = 0.004). The majority of the respondents were
      aware of The Journal's evidence-based medicine section (84%) and level-of
      evidence ratings (65%), and 20% used The Journal's evidence-based medicine
      abstracts in clinical decision-making. This increased awareness of evidence-based
      medicine was also reflected in the frequent use of Cochrane reviews in clinical
      decision-making (27% of the respondents). Surgeons who used and those who were
      aware of but did not use The Journal's evidence-based medicine abstracts or
      Cochrane reviews in clinical decision-making had significantly higher competence
      instrument scores than those who were unaware of these resources (p = 0.03 and p
      < 0.001, respectively). CONCLUSIONS: Evidence-based medicine is welcomed by Dutch
      orthopaedic surgeons. The recent emphasis on evidence-based medicine is reflected
      in an increased awareness about The Journal's evidence-based medicine section,
      levels of evidence, and the largest evidence-based medicine resource: the
      Cochrane reviews. Younger orthopaedic surgeons had better knowledge about
      evidence-based medicine. The development and use of evidence-based resources as
      well as preappraised summaries such as The Journal's evidence-based medicine
      abstracts and Cochrane reviews were perceived as the best way to move from
      opinion-based to evidence-based orthopaedic practice.

PMID- 17200329
TI  - Practice management education in orthopaedic surgical residencies.

PMID- 17200331
TI  - HER2 inhibition: from discovery to clinical practice.

PMID- 17200332
TI  - Targeting Fanconi anemia/BRCA2 pathway defects in cancer: the significance of
      preclinical pharmacogenomic models.
AB  - Defects in the Fanconi anemia (FA) pathway occur in subsets of diverse human
      cancers. The hypersensitivity of FA pathway-deficient cells to DNA interstrand
      cross-linking and possibly other agents renders these genes attractive targets
      for a genotype-based, individualized anticancer therapy. A prerequisite before
      clinical trials is the validation and quantification of this hypersensitivity in
      suitable preclinical pharmacogenomic models. In addition, the effects of
      combinational therapy need to be evaluated and novel agents sought. We discuss
      here the pitfalls and limitations in the interpretation of common FA models when
      applied to the validation of FA gene defects as therapeutic targets. In general,
      all preclinical models are prone to certain artifacts and, thus, promising
      results in a single or few models rarely translate into clinical success.
      Nevertheless, the extraordinary robustness of FA pathway-deficient cells to
      interstrand cross-linking agents, which are observable in virtually any model
      independent of species, cell type, or technique used to engineer the gene defect,
      in various in vitro and in vivo settings, renders these gene defects particularly
      attractive for targeted therapy. Clinical trials are now under way.

PMID- 17200333
TI  - Reversing hepatocellular carcinoma progression by using networked biological
      therapies.
AB  - The liver is distinguished from other tissues by (a) its detoxifying function,
      (b) its resistance to apoptosis, and (c) its regenerative response to damage.
      Hepatocellular carcinoma arises when chronic insults, such as hepatitis or iron
      overload, constitutively activate this regenerative program. Here, we propose
      that the proliferative response of the liver to damage underlies the resistance
      of hepatocellular carcinoma to cytotoxic therapy, and that hepatocellular
      carcinoma growth should therefore be more readily controlled by using a networked
      combination of noncytotoxic interventions to interrupt the damage-inducible
      regenerative pathway. To this end, hepatocellular carcinoma boasts a wealth of
      potential drug targets, including viral replication, the antiapoptotic
      immunosuppressant alpha-fetoprotein, hepatic iron overload, inflammatory
      signaling, extracellular proteases, and growth factors. By blocking these
      positive feedback loops in parallel, and so returning the host environment to a
      more normal state, epigenetic repression of tumor-suppressor gene function may be
      reversed and tumor dormancy restored. Noncytotoxic maneuvers that short circuit
      damage resistance loops may thus represent an indirect form of gene therapy
      meriting incorporation into hepatocellular carcinoma clinical trials.

PMID- 17200335
TI  - Ubiquitin COOH-terminal hydrolase 1: a biomarker of renal cell carcinoma
      associated with enhanced tumor cell proliferation and migration.
AB  - PURPOSE: Renal cell carcinoma (RCC) accounts for 2% to 3% of all malignancies. It
      represents one of the most radiation- and chemotherapy-resistant tumors and
      surgical resections are only effective in organ-defined disease. However, RCC is
      an immunogenic tumor with response rates to immunotherapies between 10% and 20%
      of the treated patients. Due to the currently inefficient therapies and the low 5
      year survival rates of RCC patients, novel diagnostic, prognostic, and
      therapeutic markers are urgently needed for this disease. EXPERIMENTAL DESIGN:
      Proteome-based approaches were used to identify (a) differentially expressed
      proteins in RCC compared with normal kidney epithelium and (b) proteins that are
      able to induce an antibody response in RCC patients. Based on these experiments,
      a promising candidate was subsequently validated by reverse transcription-PCR,
      Western blot analyses, and immunohistochemistry. In addition, functional assays
      were done in generated transfectants. RESULTS: The ubiquitin COOH-terminal
      hydrolase L1 (UCHL1) was found to be differentially expressed in both RCC lesions
      and RCC cell lines and immunoreactive using patients' sera. UCHL1 expression was
      often down-regulated in primary RCC when compared with normal kidney epithelium
      but dependent on the RCC subtype, the von Hippel-Lindau phenotype, and the tumor
      grading. Moreover, the frequency and the level of UCHL1 expression were higher in
      metastases when compared with primary RCC lesions. Gain-of-function transfectants
      exhibited a significant higher proliferation and migration rate than UCHL1
      negative RCC cells. CONCLUSIONS: UCHL1 expression seems to be associated with the
      metastatic phenotype of RCC and therefore might serve as potential biomarker for
      the diagnosis and prognosis of RCC patients.

PMID- 17200334
TI  - The histone deacetylase inhibitor suberoylanilide hydroxamic acid induces growth
      inhibition and enhances gemcitabine-induced cell death in pancreatic cancer.
AB  - PURPOSE: Pancreatic cancer is an aggressive human malignancy that is generally
      refractory to chemotherapy. Histone deacetylase inhibitors are novel agents that
      modulate cell growth and survival. In this study, we sought to determine whether
      a relatively new histone deacetylase inhibitor, suberoylanilide hydroxamic acid
      (SAHA), inhibits pancreatic cancer cell growth. EXPERIMENTAL DESIGN: The effects
      of SAHA on the growth of three pancreatic cancer cell lines (BxPC3, COLO-357, and
      PANC-1) were examined with respect to cell cycle progression, p21 induction and
      localization, and interactions with the nucleoside analogue gemcitabine. RESULTS:
      SAHA induced a G(1) cell cycle arrest in BxPC-3 cells and COLO-357 cells but not
      in PANC-1 cells. This arrest was dependent, in part, on induction of p21 by SAHA,
      as p21 was not induced in PANC-1 cells, and knockdown of p21 using small
      interfering RNA oligonucleotides nearly completely suppressed the effects of SAHA
      on cell cycle arrest in COLO-357 and partly attenuated the effects of SAHA in
      BxPC-3. COLO-357 and BxPC-3 cells, but not PANC-1 cells, were also sensitive to
      gemcitabine. In the gemcitabine-resistant PANC-1 cells, a 48-h cotreatment with
      SAHA rendered the cells sensitive to the inhibitory and proapoptotic effects of
      gemcitabine. An additive effect on growth inhibition by SAHA and gemcitabine was
      observed in COLO-357 and BxPC-3 cells. Moreover, analysis of p21 distribution in
      COLO-357 cells revealed that SAHA induced the cytoplasmic localization of both
      p21 and phospho-p21. CONCLUSIONS: These data indicate that SAHA exerts
      proapoptotic effects in pancreatic cancer cells, in part, by up-regulating p21
      and sequestering it in the cytoplasm, raising the possibility that SAHA may have
      therapeutic potential in the treatment of pancreatic cancer.

PMID- 17200336
TI  - Requirement of aryl hydrocarbon receptor overexpression for CYP1B1 up-regulation
      and cell growth in human lung adenocarcinomas.
AB  - PURPOSE: CYP1B1 and CYP1A1 expression is up-regulated by activation of the aryl
      hydrocarbon receptor (AhR) through binding of ligands such as cigarette smoke
      components. We examined the association between AhR, CYP1B1, and CYP1A1
      expression in noninvasive bronchioloalveolar carcinomas (BAC) and lung
      adenocarcinomas and investigated the effects of AhR overexpression on cell
      physiology. EXPERIMENTAL DESIGN: AhR, CYP1B1, and CYP1A1 expression was examined
      in 107 lung adenocarcinomas and 57 BAC by immunohistochemistry. AhR expression in
      lung adenocarcinoma H1355 cells was stably reduced by RNA interference (RNAi).
      AhR, CYP1B1, and CYP1A1 expression was examined using real-time reverse
      transcription-PCR. Cell physiology was evaluated by measuring anchorage
      independent growth and intracellular reactive oxygen species. RESULTS: Expression
      of AhR and CYP1A1 was associated in smoking adenocarcinoma patients, whereas
      expression of AhR and CYP1B1 was associated regardless of smoking status. The
      level of CYP1B1, but not CYP1A1, was positively associated with AhR
      overexpression in BAC. 2,3,7,8-Tetrachlorobenzo-p-dioxin-induced CYP1A1/1B1
      expression was reduced in AhR RNAi clones. In the absence of 2,3,7,8
      tetrachlorobenzo-p-dioxin, CYP1B1 mRNA levels were reduced in AhR RNAi clones,
      whereas CYP1A1 mRNA levels were barely detectable. Furthermore, anchorage
      independent growth and intracellular oxidative stress were significantly reduced
      in AhR RNAi cells. CONCLUSIONS: In the absence of exogenous AhR ligands (such as
      cigarette smoke components), AhR overexpression up-regulated the expression of
      CYP1B1 in the early stage of lung adenocarcinoma. Elevated AhR expression in lung
      adenocarcinoma cells could increase intracellular oxidative stress and promote
      cell growth, implying that disrupting AhR expression might prevent the early
      development of lung adenocarcinomas.

PMID- 17200337
TI  - Radiation effects on development of HER2-positive breast carcinomas.
AB  - PURPOSE: Neither hormone-related nor genetics risk factors have been associated
      with the development of highly proliferative HER2-positive breast carcinomas.
      Because the majority of HER2-positive tumors present the amplification of the
      oncogene, we asked whether genomic instability triggered by irradiation might be
      involved in the induction of HER2-overexpressing breast carcinomas. EXPERIMENTAL
      DESIGN: Sixty-six infiltrating breast carcinomas from patients treated with
      radiation therapy for Hodgkin's lymphoma or other pediatric solid tumors and a
      control series of 61 consecutive sporadic breast tumors were analyzed by
      immunohistochemistry for HER2 expression with HercepTest. A panel of antibodies
      against estrogen receptor, progesterone receptor, c-kit, cytokeratin 5/6, p53,
      and ki67 antigen was also used to identify differentiation subsets and molecular
      characteristics of the analyzed breast carcinomas. RESULTS: Although no
      differences between the two tumor series were found with respect to HER2
      expression scored 2+ and 3+, the percentage of 3+ HER2-positive tumors was
      significantly higher in patients irradiated during breast maturation compared
      with patients irradiated after breast maturation (35.3% versus 12.5%, P = 0.046).
      In the latter group, 52.5% of the breast carcinomas showed basal-like
      differentiation (estrogen receptor, progesterone receptor, and HER2 negative)
      versus only 5.9% in the group irradiated during breast development (P < 0.0001).
      Analysis adjusted for age confirmed the significant increase in basal-like tumor
      development in patients irradiated within 4 years of menarche, but also showed
      that the differences between patients irradiated before and after puberty in HER2
      3+ tumor frequencies are due to age-related differences in HER2 3+ tumor onset.
      CONCLUSION: Together, our data indicate that the development of HER2-positive
      tumors correlates with timing rather than type of carcinogenic hits and provide
      clear evidence that radiation is a risk factor for breast carcinomas showing
      basal-like differentiation.

PMID- 17200338
TI  - Clonality and prognostic implications of p53 and epidermal growth factor receptor
      somatic aberrations in multiple primary lung cancers.
AB  - PURPOSE: For treatment decision and prognostic applications, we evaluated
      p53/epidermal growth factor receptor (EGFR) somatic aberrations in multiple
      primary lung cancers to differentiate multifocal tumors from intrapulmonary
      metastasis. EXPERIMENTAL DESIGN: Fifty-eight multiple primary lung cancers of
      1,037 patients in a 10-year period were identified to investigate somatic
      mutations and altered expression of p53 and EGFR for clonality assessment.
      Genomic DNA was extracted from microdissected cells of paraffin-embedded multiple
      primary lung cancer tissues. Overexpression and somatic mutations in exons of p53
      (exons 5-8) and tyrosine kinase domain of EGFR (exons 18-22) were examined by
      immunohistochemical staining and DNA sequencing, respectively. RESULTS: High
      frequency of somatic mutations in p53 (33 of 58, 56.9%) and/or EGFR (44 of 58,
      75.9%) resulted in high discrimination rate of tumor clonality (50 of 58, 86.2%)
      of multiple primary lung cancers. Twenty-two cases (37.9%) were assessed as
      having the same clonality and 28 cases (48.3%) were determined as having
      different clonality, which further supported the carcinogenic theory of field
      cancerization. Notably, the occurrence of lymph node metastasis was more commonly
      observed in tumors with the same clonality (P = 0.045) and was associated with
      poor patient 5-year survival rate (P = 0.001). However, no correlation was found
      between tumor clonality and patient survival (P = 0.630). The EGFR somatic
      aberrations in 58 multiple primary lung cancers, including vascular invasion
      associated with EGFR overexpression (P = 0.012) and mutation (P = 0.025), further
      suggested the potential benefits of target therapy of inoperable multiple primary
      lung cancers. CONCLUSIONS: Our results suggest that analysis of somatic
      alterations in p53 and EGFR can significantly improve the clonality assessment
      and impact management of multiple primary lung cancer patients.

PMID- 17200339
TI  - Parthenolide, a natural inhibitor of Nuclear Factor-kappaB, inhibits lung
      colonization of murine osteosarcoma cells.
AB  - PURPOSE: The transcription factor nuclear factor-kappaB (NF-kappaB) regulates the
      expression of several genes important for tumor metastasis and is constitutively
      active in the highly metastatic murine osteosarcoma cell line LM8. Parthenolide,
      a sesquiterpene lactone, was reported to inhibit the DNA binding of NF-kappaB.
      The purpose of this study is to investigate the usefulness of parthenolide as
      target for antimetastatic therapies. EXPERIMENTAL DESIGN: We examined the effect
      of parthenolide on metastasis-associated phenotypes in vitro and in murine
      experimental lung metastasis models by s.c. and i.v. inoculation of LM8 cells.
      RESULTS: We found that parthenolide strongly induced apoptosis and inhibited cell
      proliferation and the expression of vascular endothelial growth factor in vitro.
      In the in vivo metastasis models, parthenolide treatment suppressed lung
      metastasis when treatment was initiated concurrently with s.c. or i.v.
      inoculation of tumor cells, whereas lung metastasis was not reduced when
      parthenolide was given after the homing of tumor cells. The growth of s.c. tumors
      that developed at the inoculation site was not suppressed by parthenolide. We
      also found that the genetic inhibition of NF-kappaB activity by expressing mutant
      IkappaBalpha suppressed lung metastasis in vivo but not s.c. tumor growth. This
      supports our notion that the metastasis-preventing effect of parthenolide is
      mediated at least in part by inhibition of NF-kappaB activity. CONCLUSIONS: These
      findings suggested that NF-kappaB is a potential molecular target for designing
      specific prophylactic interventions against distant metastasis and that
      parthenolide is a hopeful candidate for an antimetastatic drug.

PMID- 17200340
TI  - Expression of the hypoxia marker carbonic anhydrase 9 is associated with
      anaplastic phenotypes in meningiomas.
AB  - PURPOSE: Hypoxia in the tumor microenvironment triggers a variety of genetic and
      adaptive responses that regulate tumor growth. Tumor hypoxia is often associated
      with more malignant phenotypes, resistance to therapy, and poor survival. The
      purpose of this study was to evaluate the prevalence of hypoxia in meningiomas
      using the endogenous hypoxia marker carbonic anhydrase 9 (CA9) and to relate the
      expression of CA9 to tumor vascularity, histopathologic grade, and clinical
      variables, such as recurrent tumor status. EXPERIMENTAL DESIGN: Expression of CA9
      and CD34, an endothelial cell marker, was examined in serial paraffin-embedded
      sections by immunohistochemistry in 25 grade 1, 17 grade 2, and 20 grade 3
      meningiomas. Areas of immunoreactivity were semiquantitatively scored and
      correlated to clinical variables using Statistical Analysis System statistical
      software. RESULTS: Approximately 50% (29 of 62) of all meningiomas contained
      regions of hypoxia as judged by expression of CA9, and this expression was
      significantly associated with higher-grade histology (P = 0.001). In contrast,
      vascularity, as assessed by the percentage of vascular hotspots, was inversely
      associated with tumor grade (P = 0.023) and was not associated with CA9
      expression. Among lower-grade meningiomas, CA9 expression tended to be more
      common in recurrent tumors. CONCLUSIONS: Tumor hypoxia is an endogenous feature
      of meningiomas, and therapeutic regimens should include strategies to target the
      subpopulation of hypoxic as well as the normoxic cells within the tumor. Hypoxia
      in meningiomas is associated with an aggressive phenotype. Further studies to
      define the contribution of hypoxia to meningioma pathophysiology are warranted.

PMID- 17200341
TI  - Determination of microvessel density by quantitative real-time PCR in esophageal
      cancer: correlation with histologic methods, angiogenic growth factor expression,
      and lymph node metastasis.
AB  - PURPOSE: Angiogenesis and lymphangiogenesis are important steps in tumor growth
      and dissemination and are of prognostic importance in solid tumors. The
      determination of microvessel density (MVD) by immunohistology is subject to
      considerable variability between different laboratories and observers. We
      compared MVD determination by immunohistology and quantitative real-time PCR and
      correlated the results with clinical variables. EXPERIMENTAL DESIGN: The
      expression of endothelial antigens vascular endothelial cadherin (CD144), P1H12
      (CD146), tie-2, and VEGFR-2, and lymphatic endothelial markers VEGFR-3, Prox, and
      LYVE was assessed by quantitative PCR (qPCR) in primary surgical samples. The
      expression of angiogenetic growth factors VEGF-A, VEGF-C, VEGF-D, angiopoietin-1,
      and angiopoietin-2 was quantified by PCR and correlated with MVD and clinical
      variables. RESULTS: The expression of endothelial antigens vascular endothelial
      cadherin (CD144), P1H12 (CD146), tie-2, and VEGFR-2 correlated with each other in
      54 samples of primary esophageal cancer (P < 0.0001 for all comparisons). MVD
      determined immunohistologically by CD31 staining in a subgroup of 35 patients
      correlated significantly with the qPCR method. The expression of angiogenetic
      growth factors VEGF-A, VEGF-C, VEGF-D, angiopoietin-1, and angiopoietin-2 was
      significantly associated with MVD (P < 0.0001 for all comparisons). Analysis of
      the expression of lymphendothelial markers VEGFR-3, Prox, and LYVE revealed
      concordant results, indicating that quantification of lymphendothelial cells is
      possible by qPCR. The presence of lymph node metastasis on surgical specimens was
      significantly correlated with MVD (P < 0.003), VEGFR-2 (P < 0.048), and VEGF-C (P
      < 0.042) expression. CONCLUSIONS: These results indicate that quantification of
      MVD by qPCR in surgical samples of esophageal carcinoma yields similar results
      with immunohistology. Interestingly, the extent of angiogenesis and
      lymphangiogenesis was not related in individual tumor samples. Lymph node
      metastases could be predicted by MVD and VEGF-C expression.

PMID- 17200342
TI  - 4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates
      with pathologic grade and prognosis.
AB  - PURPOSE: Cell signaling pathways include a complex myriad of interconnected
      factors from the membrane to the nucleus, such as erbB family receptors and the
      phosphoinositide-3-kinase/Akt/mTOR and Ras-Raf-ERK cascades, which drive
      proliferative signals, promote survival, and regulate protein synthesis.
      EXPERIMENTAL DESIGN: To find pivotal factors in these pathways, which provide
      prognostic information in malignancies, we studied 103 human breast tumors with
      an immunohistochemical profile, including total and phosphorylated (p) proteins:
      human epidermal growth factor receptor 2 (HER2), epidermal growth factor
      receptor, extracellular signal-regulated kinase 1/2, Akt, 4E-binding protein 1
      (4EBP1), eukaryotic initiation factor 4E, phosphorylated ribosomal protein S6
      kinase 1, phosphorylated ribosomal protein S6, and Ki67. Western blot and reverse
      lysate protein arrays were also done in a subset of tumors. RESULTS:
      Significantly, activation of the phosphoinositide-3-kinase/Akt/mTOR cascade was
      detected in a high proportion of tumors (41.9%). Tumors with HER2 overexpression
      showed higher p-Akt as compared with negative tumors (P < 0.001). Levels of p-Akt
      correlated with the downstream molecules, p-4EBP1 (P = 0.001) and p-p70S6K (P =
      0.05). Although 81.5% of tumors expressed p-4EBP1, in 16.3% of these tumors,
      concomitant activation of the upstream factors was not detected. Interestingly, p
      4EBP1 was mainly expressed in poorly differentiated tumors (P < 0.001) and
      correlated with tumor size (P < 0.001), presence of lymph node metastasis (P =
      0.002), and locoregional recurrences (P = 0.002). Coexpression of p-4EBP1 and p
      eIF4G correlated with a high tumor proliferation rate (P = 0.012). CONCLUSION: In
      this study, p-4EBP1 was the main factor in signaling pathways that associate with
      prognosis and grade of malignancy in breast tumors. Moreover, p-4EBP1 was
      detected in both HER2-positive and HER2-negative tumors. This factor seems to be
      a channeling point at which different upstream oncogenic alterations converge and
      transmit their proliferative signal, modulating protein translation.

PMID- 17200343
TI  - Caveolin 1 is overexpressed and amplified in a subset of basal-like and
      metaplastic breast carcinomas: a morphologic, ultrastructural,
      immunohistochemical, and in situ hybridization analysis.
AB  - PURPOSE: The distribution and significance of caveolin 1 (CAV1) expression in
      different breast cell types and role in breast carcinogenesis remain poorly
      understood. Both tumor-suppressive and oncogenic roles have been proposed for
      this protein. The aims of this study were to characterize the distribution of
      CAV1 in normal breast, benign breast lesions, breast cancer precursors, and
      metaplastic breast carcinomas; to assess the prognostic significance of CAV1
      expression in invasive breast carcinomas; and to define whether CAV1 gene
      amplification is the underlying genetic mechanism driving CAV1 overexpression in
      breast carcinomas. EXPERIMENTAL DESIGN: CAV1 distribution in frozen and paraffin
      embedded whole tissue sections of normal breast was evaluated using
      immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1
      expression was immunohistochemically analyzed in benign lesions, breast cancer
      precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive
      breast carcinomas from patients treated with surgery followed by anthracycline
      based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by
      chromogenic in situ hybridization. RESULTS: In normal breast, CAV1 was expressed
      in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal
      epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39
      metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the
      later cohort, CAV1 expression was significantly associated with 'basal-like'
      immunophenotype and with shorter disease-free and overall survival on univariate
      analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1
      expression. CONCLUSIONS: The concurrent CAV1 amplification and overexpression
      call into question its tumor-suppressive effects in basal-like breast carcinomas.

PMID- 17200344
TI  - Inactivation of SMAD4 tumor suppressor gene during gastric carcinoma progression.
AB  - PURPOSE: Mothers against decapentaplegic homologue 4 (SMAD4) is a tumor
      suppressor gene associated with gastrointestinal carcinogenesis. The aim of the
      present study is to more precisely characterize its role in the development and
      progression of human gastric carcinoma. EXPERIMENTAL DESIGN: The expression of
      SMAD4 was investigated in 283 gastric adenocarcinomas and related lesions, as
      well as in 9 gastric carcinoma cell lines. We also analyzed the methylation
      status of SMAD4 gene by using methylation-specific PCR, examined loss of
      heterozygosity (LOH) of this gene locus by using a vicinal marker, and detected
      exon mutation of SMAD4 through exon-by-exon amplification. Moreover, we assessed
      whether MG132, a proteasome inhibitor, affected the SMAD4 protein level. RESULTS:
      We found loss of SMAD4 protein expression in the cytoplasm (36 of 114, 32%) and
      in the nucleus (46 of 114, 40%) of gastric cancer cells. The loss of nuclear
      SMAD4 expression in primary tumors correlated significantly with poor survival,
      and was an independent prognostic marker in multivariate analysis. We also found
      a substantial decrease in SMAD4 expression at both the RNA and protein level in
      several human gastric carcinoma cell lines. In addition, we found that LOH (20 of
      70, 29%) and promoter hypermethylation (4 of 73, 5%) were associated with the
      loss of SMAD4 expression. SMAD4 protein levels were also affected in certain
      gastric carcinoma cell lines following incubation with MG132. CONCLUSION: Taken
      together, our results indicate that the loss of SMAD4, especially loss of nuclear
      SMAD4 expression, is involved in gastric cancer progression. The loss of SMAD4 in
      gastric carcinomas was due to several mechanisms, including LOH,
      hypermethylation, and proteasome degradation.

PMID- 17200345
TI  - Clonal and parallel evolution of primary lung cancers and their metastases
      revealed by molecular dissection of cancer cells.
AB  - PURPOSE: Several models of cancer progression, including clonal evolution,
      parallel evolution, and same-gene models, have been proposed to date. The purpose
      of this study is to investigate the authenticity of these models by comparison of
      accumulated genetic alterations between primary and corresponding metastatic lung
      cancers. EXPERIMENTAL DESIGN: A whole-genome allelic imbalance scanning using a
      high-resolution single nucleotide polymorphism array and mutational analysis of
      the p53, EGFR, and KRAS genes were done on eight sets of primary and metastatic
      lung cancers. Based on the genotype data, the natural history of each case was
      deduced, and candidate metastasis suppressor loci were determined. RESULTS: Five
      to 20 chromosomal regions showed allelic imbalance in each tumor. Accumulated
      genetic alterations were similar between primary and corresponding metastatic
      tumors, and the majority(>67%) of genetic alterations detected in metastatic
      tumors was also detected in the corresponding primary tumors. On the other hand,
      in seven of the eight cases, there were genetic alterations accumulated only in
      metastatic tumors. Among these alterations, allelic imbalances at chromosome
      11p15 and 11p11-p13 regions were the most frequent ones (4 of 8, 50%). Likewise,
      four cases showed genetic alterations detected only in primary tumors.
      CONCLUSIONS: The natural history of each case indicated that the process of
      metastasis varies among cases, and that all three models are applicable to lung
      cancer progression. According to the clonal and parallel evolution models, it is
      possible that a metastasis suppressor gene(s) for lung cancer is present on
      chromosome 11p.

PMID- 17200346
TI  - Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant
      progression of multiple human cancers.
AB  - PURPOSE: CLIC4, a member of a family of intracellular chloride channels, is
      regulated by p53, c-Myc, and tumor necrosis factor-alpha. Regulation by factors
      involved in cancer pathogenesis, together with the previously shown proapoptotic
      activity of CLIC4, suggests that the protein may have a tumor suppressor
      function. To address this possibility, we characterized the expression profile,
      subcellular localization, and gene integrity of CLIC4 in human cancers and
      determined the functional consequences of CLIC4 expression in tumor epithelium
      and stromal cells. EXPERIMENTAL DESIGN: CLIC4 expression profiles were analyzed
      by genomics, proteomics, bioinformatics, and tissue microarrays. CLIC4
      expression, as a consequence of crosstalk between stroma and epithelium, was
      tested in vitro by coculture of breast epithelial tumor cells and normal
      fibroblasts, and the functional consequences of CLIC4 expression was tested in
      vivo in xenografts of human breast tumor cell lines reconstituted with CLIC4 or
      mixed with fibroblasts that overexpress CLIC4 transgenically. RESULTS: In cDNA
      arrays of matched human normal and tumor tissues, CLIC4 expression was reduced in
      renal, ovarian, and breast cancers. However, CLIC4 protein levels were variable
      in tumor lysate arrays. Transcript sequences of CLIC4 from the human expressed
      sequence tag database and manual sequencing of cDNA from 60 human cancer cell
      lines (NCI60) failed to reveal deletion or mutations in the CLIC4 gene. On
      matched tissue arrays, CLIC4 was predominantly nuclear in normal human epithelial
      tissues but not cancers. With advancing malignant progression, CLIC4 staining
      became undetectable in tumor cells, but expression increased in stromal cells
      coincident with up-regulation of alpha-smooth muscle actin, suggesting that CLIC4
      is up-regulated in myofibroblasts. Coculture of cancer cells and fibroblasts
      induced the expression of both CLIC4 and alpha-smooth muscle actin in fibroblasts
      adjacent to tumor nests. Introduction of CLIC4 or nuclear targeted CLIC4 via
      adenovirus into human breast cancer xenografts inhibited tumor growth, whereas
      overexpression of CLIC4 in stromal cells of xenografts enhanced tumor growth.
      CONCLUSION: Loss of CLIC4 in tumor cells and gain in tumor stroma is common to
      many human cancers and marks malignant progression. Up-regulation of CLIC4 in
      tumor stroma is coincident with myofibroblast conversion, generally a poor
      prognostic indicator. Reactivation and restoration of CLIC4 in tumor cells or the
      converse in tumor stromal cells could provide a novel approach to inhibit tumor
      growth.

PMID- 17200347
TI  - High human papillomavirus oncogene mRNA expression and not viral DNA load is
      associated with poor prognosis in cervical cancer patients.
AB  - PURPOSE: Cervical cancer is now known to be caused by infection with an oncogenic
      type of the human papillomavirus (HPV). However, little is known about the
      continued role of HPV once cancer has been established. Here, we describe the
      quantitative relation between HPV DNA copy number and mRNA expression of the
      viral oncogenes (E6 and E7) and the prognostic value of both measures in cervical
      cancer patients. EXPERIMENTAL DESIGN: We studied the number of viral DNA copies
      and the level of HPV E6/E7 mRNA expression in 75 HPV 16-positive or HPV 18
      positive International Federation of Gynecology and Obstetrics stage Ib and IIa
      cervical cancer patients. Measurements were done with quantitative PCR. DNA copy
      number analysis was done on pure tumor cell samples enriched with flow sorting.
      mRNA expression data were compensated for the percentage of tumor cells included.
      RESULTS: The number of viral DNA copies was not predictive of survival in
      cervical cancer patients. In contrast, high HPV E6/E7 mRNA expression was
      strongly related to an unfavorable prognosis (P = 0.006). In a multivariate Cox
      model for overall survival, including all known prognostic variables and
      stratified for HPV type, the level of E6/E7 mRNA expression was an independent
      prognostic indicator, second only to lymph node status. No correlation was
      observed between DNA copy number and the level of HPV E6/E7 mRNA expression,
      which reflects that not all DNA copies are equally transcriptionally active.
      CONCLUSIONS: Cervical cancer patients with high HPV E6/E7 oncogene mRNA
      expression have a worse survival independently from established prognostic
      factors.

PMID- 17200348
TI  - Quantification of the heterogeneity in breast cancer cell lines using whole-cell
      impedance spectroscopy.
AB  - PURPOSE: Quantification of the heterogeneity of tumor cell populations is of
      interest for many diagnostic and therapeutic applications, including determining
      the cancerous stage of tumors. We attempted to differentiate human breast cancer
      cell lines from different pathologic stages and compare that with a normal human
      breast tissue cell line by characterizing the impedance properties of each cell
      line. EXPERIMENTAL DESIGN: A microelectrical impedance spectroscopy system has
      been developed that can trap a single cell into an analysis cavity and measure
      the electrical impedance of the captured cell over a frequency range from 100 Hz
      to 3.0 MHz. Normal human breast tissue cell line MCF-10A, early-stage breast
      cancer cell line MCF-7, invasive human breast cancer cell line MDA-MB-231, and
      metastasized human breast cancer cell line MDA-MB-435 were used. RESULTS: The
      whole-cell impedance signatures show a clear difference between each cell line in
      both magnitude and phase of the electrical impedance. The membrane capacitance
      calculated from the impedance data was 1.94 +/- 0.14, 1.86 +/- 0.11, 1.63 +/-
      0.17, and 1.57 +/- 0.12 muF/cm(2) at 100 kHz for MCF-10A, MCF-7, MDA-MB-231, and
      MDA-MB-435, respectively. The calculated resistance for each cancer cell line at
      100 kHz was 24.8 +/- 1.05, 24.8 +/- 0.93, 24.9 +/- 1.12, and 26.2 +/- 1.07 MOhm,
      respectively. The decrease in capacitances of the cancer cell lines compared with
      that of the normal cell line MCF-10A was 4.1%, 16.0%, and 19.1%, respectively, at
      100 kHz. CONCLUSIONS: These findings suggest that microelectrical impedance
      spectroscopy might find application as a method for quantifying progression of
      cancer cells without the need for tagging or modifying the sampled cells.

PMID- 17200349
TI  - Clinical relevance of E2F family members in ovarian cancer--an evaluation in a
      training set of 77 patients.
AB  - PURPOSE: The major obstacle in treating ovarian cancer is the rapid development
      of platinum resistance during therapy. Deregulation of members of the E2F family
      of transcription factors is crucially involved in carcinogenesis and probably in
      mechanisms underlying platinum resistance. We therefore investigated the
      relevance of the whole set of E2F family members in predicting clinical outcome
      and their significance in predicting platinum resistance. EXPERIMENTAL DESIGN:
      Real-time PCR of all E2F family members was done from 77 ovarian carcinomas,
      defined as our training set, and 8 healthy control samples. The correlation with
      clinicopathologic characteristics, platinum resistance, and survival was
      investigated. Furthermore, the cross-talk of E2F family members was assessed for
      its value in predicting survival and platinum resistance. RESULTS: The
      proliferation-promoting E2F1 and E2F2 were associated with grade 3 tumors and
      residual disease >2 cm in diameter after initial surgery. Survival analyses
      showed low expression of E2F1 or E2F2 to be significantly associated with
      favorable disease-free and overall survival (E2F1, P = 0.039 and 0.047,
      respectively; E2F2, P = 0.009 and 0.006, respectively). In contrast, high
      expression of inhibiting E2F4 or E2F7 predicted favorable disease-free and
      overall survival (E2F4, P = 0.047 and 0.042, respectively; E2F7, P = 0.048 and
      0.042, respectively). A high E2F2 to E2F4 ratio was the most valuable prognostic
      variable for disease-free survival in multivariate analysis (hazard ratio, 6.494;
      P = 0.002). Tumors considered platinum resistant were associated with lower E2F4
      and E2F7 expression (P = 0.012 and 0.009, respectively) compared with platinum
      sensitive tumors. Again, ratios of E2F1 or E2F2 to E2F7 were the most favorable
      variables in predicting platinum resistance. CONCLUSIONS: We here show that
      deregulation of both proliferation-promoting and proliferation-inhibiting E2F
      transcription factors and their cross-talk is crucially involved in the tumor
      biology of ovarian cancer and influences clinical outcome. Furthermore, down
      regulation of E2F7 may contribute to mechanisms underlying platinum resistance,
      and calculation of ratios of proliferation-promoting E2F1 to E2F7 could serve as
      a putative predictor of platinum resistance.

PMID- 17200350
TI  - Expression of adipose differentiation-related protein: a predictor of cancer
      specific survival in clear cell renal carcinoma.
AB  - PURPOSE: We recently found that adipose differentiation-related protein (ADFP) is
      a potential diagnostic and prognostic biomarker for clear cell subtype renal cell
      carcinoma (RCC). To further evaluate the correlation between ADFP expression
      levels and clinicopathologic characteristics and patient outcome, we
      retrospectively examined patients with clear cell RCC. EXPERIMENTAL DESIGN: A
      series of 432 consecutive patients with sporadic clear cell RCC who underwent
      nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP
      expression levels in the primary tumors and in 18 metastases were measured by
      real-time quantitative PCR. The clinicopathologic and prognostic data were
      collected, as well as the von Hippel-Lindau disease (VHL) gene alteration status
      in selected cases. RESULTS: ADFP expression was apparently high in cases without
      a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL
      alteration-positive clear cell RCC, whereas it was down-regulated in
      undifferentiated tumors with a spindle/pleomorphic component or metastatic
      lesions. Univariate analyses showed that high ADFP expression was associated with
      better cancer-specific survival and cancer-free survival. Further Cox
      multivariate analyses combined with the split-sample validation method showed
      that ADFP expression still remains an independent predictor for cancer-specific
      survival in all tumor stages and in advanced metastatic cases, whereas the
      predictive value of ADFP expression for cancer recurrence is rather weak.
      CONCLUSIONS: The ADFP expression may represent the tumor differentiation status,
      and the detection of the expression levels provides useful prognostic information
      for cancer-specific survival in patients with clear cell RCC.

PMID- 17200351
TI  - Two distinct types of blood vessels in clear cell renal cell carcinoma have
      contrasting prognostic implications.
AB  - PURPOSE: Intratumoral microvascular density (MVD) has been controversial as an
      indicator of prognosis in clear cell renal cell carcinoma (CCRCC). Classification
      of the intratumoral blood vessels based on differential expressions of blood
      vessel markers has not been correlated with patient prognosis in CCRCC. In this
      study, we aimed to evaluate the association of different categories of blood
      vessels with the patients' outcomes. EXPERIMENTAL DESIGN: Seventy-eight CCRCC
      patients who underwent nephrectomy alone were enrolled. Paraffin-embedded CCRCC
      tissues, together with 16 nonmalignant kidney cortex tissues, were used in tissue
      microarray analyses and conventional section analyses. The characteristics of
      intratumoral blood vessels were identified by multiple blood vessel markers and
      pericyte markers. A computerized image analysis program was used to
      quantitatively calculate the vascular density. RESULTS: Two distinct types of
      microvessels were identified in CCRCC: undifferentiated (CD31(+)/CD34(-)) and
      differentiated (CD34(+)) vessels. A higher undifferentiated MVD significantly
      correlated with higher tumor grades and shorter patient survival. In contrast, a
      higher differentiated MVD significantly correlated with lower tumor grade and
      longer survival. Multivariate analyses showed that undifferentiated MVD was an
      independent prognostic factor for patient survival. An inverse correlation
      between undifferentiated MVD and differentiated MVD was also identified in CCRCC.
      CONCLUSIONS: This is the first report showing distinct types of vasculature in
      CCRCC correlated with contrasting prognoses. A refined classification of CCRCC
      based on vasculature is therefore important for evaluating prognosis, and it may
      also have therapeutic implications.

PMID- 17200353
TI  - Risk of second cancer in nongastric marginal zone B-cell lymphomas of mucosa
      associated lymphoid tissue: a population-based study from northern Italy.
AB  - PURPOSE: The aim of this study was to define the risk of second cancer in
      nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT).
      EXPERIMENTAL DESIGN: We considered for the analysis 157 patients with a confirmed
      histology of marginal zone B-cell lymphoma of MALT, presenting with a clinically
      prevalent extranodal site of disease, except for stomach. All patients came from
      two hematologic institutions of Northern Italy. We compared the occurrence of
      second cancer with respect to the general population by calculating the
      standardized incidence ratio, with the age- and sex-specific incidence rates of a
      cancer registry of Northern Italy (Lombardia) as a reference. RESULTS: A history
      of solid neoplasia was present in 29 (18%) patients for a total number of 30
      neoplasms: 25 solid tumors, 2 hematologic diseases (1 Hodgkin's lymphoma and 1
      essential thrombocythemia), and 3 nonmelanoma in situ skin cancers. In 4
      patients, the site of cancer and lymphoma was the same. In 21 cases the solid
      tumor preceded the MALToma, in 3 the neoplasm was concomitant, whereas in 6 it
      was subsequent. For the entire group, the standardized incidence ratio of an
      additional malignancy was 0.8 [95% confidence interval (95% CI), 0.55-1.17; P =
      0.2]. After excluding nonmelanoma skin cancer, the standardized incidence ratio
      of a second tumor was 0.75 (95% CI, 0.5-1.12; P = 0.2). After excluding all
      previous malignancies, the standardized incidence ratio of a second cancer was
      1.32 (95% CI, 0.69-2.55; P = 0.4). The comparison of risks between males and
      females was not significant in each group analysis. CONCLUSIONS: Patients with
      nongastric MALT lymphomas are not at increased risk for other neoplasms compared
      with the general population of the same geographic area.

PMID- 17200352
TI  - Pathologic and molecular heterogeneity in imatinib-stable or imatinib-responsive
      gastrointestinal stromal tumors.
AB  - PURPOSE: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the
      intestinal tract. Nearly all tumors express KIT protein, and most have an
      activating mutation in either KIT or PDGFRA. Therapy with selective tyrosine
      kinase inhibitors achieves a partial response or stable disease in approximately
      80% of patients with advanced GIST. However, after an initial clinical response,
      some patients develop imatinib resistance. Our goal was to investigate the
      spectrum of pathologic response and molecular alterations in a group of GIST
      patients, clinically defined as having imatinib-stable/imatinib-responsive
      lesions, who underwent surgical resection. EXPERIMENTAL DESIGN: Forty-three tumor
      nodules from 28 patients were available for pathologic and molecular analysis,
      which included genotyping for primary and secondary KIT/PDGFRA-mutations, cell
      cycle alterations, and biochemical activation status of KIT and downstream
      targets. The transcriptional changes of a subset of these tumors were compared
      with a group of imatinib-naive GISTs on a U133A Affymetrix expression platform.
      RESULTS: The histologic response did not correlate with imatinib therapy duration
      or with proliferative activity. Second-site KIT mutation was identified in only
      one tumor nodule. Activation of KIT and downstream targets was consistent in all
      tumors analyzed. Ultrastructurally, a subset of tumors showed a smooth muscle
      phenotype, which correlated with overexpression of genes involved in muscle
      differentiation and function. CONCLUSIONS: The histologic response to imatinib is
      heterogeneous and does not correlate well with clinical response. Second-site KIT
      mutations are rare in imatinib-responsive GISTs compared with imatinib-resistant
      tumors. The gene signature of imatinib-response in GISTs showed alterations of
      cell cycle control as well as up-regulation of genes involved in muscle
      differentiation and function.

PMID- 17200354
TI  - Prognostic value of tumor architecture, tumor-associated vascular
      characteristics, and expression of angiogenic molecules in pancreatic endocrine
      tumors.
AB  - PURPOSE: It is difficult to predict the biological behavior of pancreatic
      endocrine tumors (PETs). Our aim was to evaluate the prognostic significance of
      certain variables in PETs. EXPERIMENTAL DESIGN: The following variables were
      examined in 37 patients with PETs and then compared with other clinicopathologic
      characteristics: histologic tumor structure; microvessel density (MVD) measured
      by three different methods, including a unique method involving calculation of
      solid area MVD; endothelial proliferation; and the immunohistochemical expression
      of vascular endothelial growth factor-A and CXC chemokine CXCL-12. Intratumoral
      vascular structures were analyzed by double immunofluorescence using 30-microm
      thick sections. RESULTS: The presence of focal and intensive solid growth of
      tumor cells (large solid nests; P = 0.003), low solid area MVD (P = 0.002), a
      high endothelial cell proliferation index (EPI; P = 0.005), and high expression
      of CXCL-12 in PET cells (P = 0.018) were significant unfavorable prognostic
      indicators. The predominant structure of the overall tumor histology and the
      expression of vascular endothelial growth factor-A did not separate aggressive
      PETs. In areas of focal solid growth, tumor-associated blood vessels had
      obviously low MVD and high EPI, and their structures were poorly formed with
      highly abnormal features, in comparison with other areas. High expression of CXCL
      12 in tumor cells was significantly associated with variables representing tumor
      growth, hematogenous tumor spread, low MVD, high EPI, and the presence of large
      solid nests. CONCLUSIONS: This study has provided novel findings on the
      prognostic features of tumor architecture and tumor-associated angiogenesis in
      PETs. CXCL-12 is the first candidate molecule in association with neoangiogenesis
      in PETs.

PMID- 17200355
TI  - Nonsynonymous coding single-nucleotide polymorphisms spanning the genome in
      relation to glioblastoma survival and age at diagnosis.
AB  - PURPOSE: Our aim was to discover possible inherited factors associated with
      glioblastoma age at diagnosis and survival. Although new genotyping technologies
      allow greatly expanded exploration of such factors, they pose many challenges.
      EXPERIMENTAL DESIGN: In this pilot study, we (a) genotyped 112 newly diagnosed
      glioblastoma patients ascertained through a population-based study (group 1) with
      the ParAllele assay panel of approximately 10,000 nonsynonymous coding single
      nucleotide polymorphisms (SNP), (b) used several statistical and bioinformatic
      techniques to identify 17 SNPs potentially related to either glioblastoma age at
      diagnosis or survival, and (c) genotyped 16 of these SNPs using conventional PCR
      methods in an independent group of 195 glioblastoma patients (group 2). RESULTS:
      In group 2, only one of the 16 SNPs, rs8057643 (located on 16p13.2), was
      significantly associated with glioblastoma age at diagnosis (nominal P = 0.0017;
      Bonferroni corrected P = 0.054). Median ages at diagnosis for those with 0, 1, or
      2 T alleles were 66, 57, and 59 years in group 1 and 64, 57, and 55 years in
      group 2 (combined P = 0.001). Furthermore, Cox regression analyses of time to
      death with number of T alleles adjusted for gender and patient group yielded a
      hazard ratio of 0.82 (95% confidence interval, 0.68-0.98; P = 0.03). CONCLUSIONS:
      Although limited by a relatively small sample size, this pilot study, using well
      characterized, unambiguous disease characteristics, illustrates the necessity of
      independent replication owing to the likelihood of false positives. Several other
      challenges are discussed, including attempts to incorporate information on the
      potential functional importance of SNPs in genome-disease association studies.

PMID- 17200356
TI  - Expression of cellular FLICE inhibitory protein, caspase-8, and protease
      inhibitor-9 in Ewing sarcoma and implications for susceptibility to cytotoxic
      pathways.
AB  - PURPOSE: Ewing sarcoma is a common pediatric bone tumor with an unfavorable
      prognosis for metastatic or recurrent disease. Cellular immunotherapy may provide
      new treatment options and depends on the cytolytic death receptor and
      perforin/granzyme pathways. Expression of death receptor pathway inhibitor
      cellular FLICE inhibitory protein (cFLIP), initiator caspase-8, and granzyme B
      inhibitor protease inhibitor-9 (PI-9) have been reported to determine
      susceptibility to cell- and chemotherapy-mediated killing in several tumor types.
      Here, we have studied their in vitro and in vivo expression in Ewing sarcoma and
      the implications for susceptibility to cytotoxicity. EXPERIMENTAL DESIGN: Ewing
      sarcoma cell lines (n = 8) were tested for cFLIP, PI-9, and caspase-8 expression.
      Functional significance was tested by anti-Fas antibody (death receptor pathway)
      or natural killer cell (perforin/granzyme pathway) treatment.
      Immunohistochemistry was done on 28 sections from 18 patients. In half of the
      cases, sequential material, including metastases, was available. RESULTS:
      Although all tested Ewing sarcoma cell lines expressed cFLIP, resistance to
      CD95/Fas-mediated apoptosis was only observed in two cell lines lacking caspase-8
      expression. PI-9 was expressed at low levels in four of eight Ewing sarcoma cell
      lines, but positive cell lines remained susceptible to perforin/granzyme-mediated
      killing. In primary Ewing sarcoma, including metastases, cFLIP was abundantly
      expressed in 18 of 18 patients. Caspase-8 was expressed in all patients but
      showed more intertumoral and intratumoral variation in both intensity and
      heterogeneity of staining. PI-9, in contrast, was undetectable. CONCLUSIONS: The
      expression patterns of cFLIP, caspase-8, and the absence of PI-9 provide a
      rationale to preferentially exploit the perforin/granzyme pathway in cytotoxic
      therapies against Ewing sarcoma.

PMID- 17200357
TI  - Alum with interleukin-12 augments immunity to a melanoma peptide vaccine:
      correlation with time to relapse in patients with resected high-risk disease.
AB  - PURPOSE: We attempted to augment immunity to melanoma antigens using interleukin
      12 (IL-12) with aluminum hydroxide (alum) for sustained release or granulocyte
      macrophage colony-stimulating factor (GM-CSF) added to a multipeptide vaccine.
      EXPERIMENTAL DESIGN: Sixty patients with high-risk resected melanoma were
      randomized to receive melanoma peptides gp100(209-217) (210M), MART-1(26-35)
      (27L), and tyrosinase(368-376) (370D) with adjuvant Montanide ISA 51 and either
      IL-12 at 30 ng/kg with alum (group A), IL-12 at 100 ng/kg with alum (group B), or
      IL-12 at 30 ng/kg with 250 mug GM-CSF (group C). RESULTS: Three patients had
      stage IIC (5%), 50 had stage III (83%), and 7 had stage IV (12%) melanoma. Most
      toxicities were grade 1/2 and resolved rapidly. Significant toxicity included
      grade 3 colitis and visual changes and grade 3 headache resolving after stopping
      IL-12 but continuing peptide vaccine. A higher rate of post-vaccine 6-month
      immune response to gp100 and MART-1 was observed in group A (15 of 19) or B (19
      of 20) that received IL-12 plus alum versus group C with IL-12/GM-CSF (4 of 21; P
      < 0.001). Post-vaccine enzyme-linked immunospot response rates to peptide
      analogues in group B were higher than group A (P = 0.031 for gp100 and P = 0.010
      for MART-1); both were higher than group C (P < 0.001 for gp100 and P < 0.026 for
      MART-1). With a median of 24 months of follow-up, 23 patients have relapsed. Post
      vaccine immune response to MART-1 was associated with relapse-free survival (P =
      0.012). CONCLUSIONS: IL-12 with alum augmented an immune response to melanoma
      antigens compared with IL-12 with GM-CSF. Immune response was associated with
      time to relapse.

PMID- 17200358
TI  - Increased dose density is feasible: a pilot study of adjuvant epirubicin and
      cyclophosphamide followed by paclitaxel, at 10- or 11-day intervals with
      filgrastim support in women with breast cancer.
AB  - PURPOSE: Because Cancer and Leukemia Group B 9741 trial showed a benefit for
      every 14-day administration of chemotherapy compared with every 21-day treatment,
      we hypothesized that even greater dose density would be more effective. We
      conducted a pilot trial to assess the feasibility of dose-dense chemotherapy
      consisting of a standard regime at 10- to 11-day intervals in the
      adjuvant/neoadjuvant setting. A 2-day window was allowed for scheduling
      logistics. EXPERIMENTAL DESIGN: Thirty-nine women with early-stage breast
      carcinoma were accrued from April 2004 to October 2004. Median age was 47 years
      (range, 26-67 years). Patients received therapy with 100 mg/m(2) epirubicin and
      600 mg/m(2) cyclophosphamide (EC) q 10 to 11 days for four cycles followed by 175
      mg/m(2) paclitaxel q 10 to 11 days for four cycles, all with filgrastim support
      (300 microg s.c. daily) from day 2 to 24 h before the next treatment. RESULTS:
      Thirty-five (90%) patients completed all planned therapy. The median
      intertreatment interval was 10 days (range, 8-28 days). Cycles (80.7%) were
      delivered at no more than 10- to 11-day intervals. There were five dose
      reductions of 25% for grade 3 nonhematologic toxicity in five patients. Six (16%)
      patients developed febrile neutropenia defined as temperature >38 degrees C with
      absolute neutrophil count <1,000/microL. All febrile neutropenia was during
      therapy with EC. Other grade 3 toxicities included bone pain, hand and foot
      syndrome, neuropathy, mucositis, nausea, and vomiting. CONCLUSIONS: Therapy with
      EC for four cycles followed by paclitaxel for four cycles at 10- to 11-day
      intervals is feasible. The approximately 30% reduction in intertreatment interval
      compared with every 14-day treatment could increase the efficacy of adjuvant
      chemotherapy.

PMID- 17200360
TI  - Clinical and in vitro studies of imatinib in advanced carcinoid tumors.
AB  - PURPOSE: Effective systemic therapy options for carcinoid tumors are lacking. We
      conducted in vitro studies and a phase II clinical trial to explore the activity
      of imatinib in carcinoid tumors. EXPERIMENTAL DESIGN: Cells of the human
      bronchial carcinoid cell line NCI-H727 and the human pancreatic carcinoid cell
      line BON-1 were treated with increasing concentrations of imatinib using standard
      procedures to assess in vitro growth-inhibitory activity. A clinical trial using
      a two-stage phase II design to assess the response rate and safety profile of
      imatinib at a dose of 400 mg given twice daily in patients with advanced
      carcinoid tumors was completed. RESULTS: In both cell lines, there was a dose-
      and time-dependent cytotoxic effect. The clinical trial enrolled 27 evaluable
      patients. Median duration on trial was 16 weeks. One patient had a partial
      response, 17 had stable disease, and 9 had progressive disease by the Response
      Evaluation Criteria in Solid Tumors criteria. Median progression-free survival
      time was 24 weeks. Median overall survival is 36 months. Seven patients who
      achieved a biochemical response had a superior progression-free survival time
      compared with patients without biochemical response (115 weeks compared with 24
      weeks; P = 0.003). An increase in plasma basic fibroblast growth factor was
      associated with a shorter progression-free survival duration (P = 0.02).
      CONCLUSIONS: Our data suggest that imatinib is active in vitro and has a modest
      clinical activity in carcinoid patients. Changes in tumor markers may help select
      patients who are likely to benefit from therapy.

PMID- 17200359
TI  - Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and
      cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal
      growth factor receptor 2-positive operable breast cancer: an update of the
      initial randomized study population and data of additional patients treated with
      the same regimen.
AB  - PURPOSE: Findings from our previously published phase III randomized trial showed
      a high pathologic complete remission (CR) rate in patients with human epidermal
      growth factor receptor 2-positive breast cancer after the concurrent
      administration of trastuzumab and paclitaxel, followed by concurrent trastuzumab
      and 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) preoperative
      chemotherapy. The safety and efficacy data of initial population were updated,
      with inclusion of additional experience with the same therapy. STUDY DESIGN: The
      initial randomized study population of 42 patients were randomly assigned to
      either four cycles of paclitaxel followed by four cycles of FEC or to the same
      chemotherapy with simultaneous weekly trastuzumab for 24 weeks. All data were
      updated through November 2005. RESULTS: Pretreatment characteristics of the
      initial patients and of the second cohort were similar. In the second cohort,
      pathologic CR rate was 54.5% (95% confidence interval, 32.2-75.6%) and the
      pathologic CR rate among all patients treated with chemotherapy plus trastuzumab
      was 60% (95% confidence interval, 44.3-74.3%). Three patients in the chemotherapy
      only group have recurred, and one has died. There has been no recurrences in the
      patients randomized to chemotherapy plus trastuzumab, and the estimated disease
      free survival at 1 and 3 years was 100% (P = 0.041). In additional cohort treated
      with chemotherapy and trastuzumab at the median follow-up of 16.3 months, no
      patients had recurred. No new safety concerns were observed in this study.
      CONCLUSION: Our expanded cardiac safety data and the updated efficacy data showed
      that the natural history of this subset of breast cancer patients can be
      substantially modified by this treatment approach.

PMID- 17200361
TI  - Obesity and sex steroids during gonadotropin-releasing hormone agonist treatment
      for prostate cancer.
AB  - PURPOSE: To evaluate effects of obesity on sex steroid levels during treatment
      with a gonadotropin-releasing hormone agonist in men with prostate cancer.
      EXPERIMENTAL DESIGN: Forty-nine hormone-naive men with recurrent or locally
      advanced prostate cancer were included in the analyses. All subjects were treated
      with leuprolide 3-month depot for 48 weeks. Serum levels of estradiol, sex
      hormone-binding globulin, total testosterone, and free testosterone were assessed
      at baseline, 24 weeks, and 48 weeks. Subjects were categorized by body mass index
      (BMI) and percent body fat. RESULTS: Pretreatment serum sex hormone-binding
      globulin and total testosterone levels were significantly lower in overweight and
      obese men than in men with normal BMI. In the overall study population, mean
      serum testosterone concentrations decreased from 372 +/- 18 ng/dL at baseline to
      13 +/- 1 ng/dL at week 48 (P < 0.001). Free testosterone decreased from 6.75 +/-
      0.33 ng/dL at baseline to 0.21 +/- 0.02 ng/dL at week 48 (P < 0.001). During
      treatment with leuprolide, obese men had significantly higher total and free
      testosterone levels than men with normal BMI. Compared with normal men, total and
      free testosterone levels during treatment were 1.8-fold and 2.3-fold higher in
      obese men. Similar results were observed when subjects were categorized by body
      fat. CONCLUSIONS: Despite lower pretreatment serum testosterone levels, obese men
      have higher total and free testosterone levels during leuprolide treatment than
      men with normal BMI. These differences may contribute to the association between
      obesity and increased prostate cancer mortality.

PMID- 17200363
TI  - Antitumor activity of novel indirubin derivatives in rat tumor model.
AB  - PURPOSE: The novel indirubin derivatives 5'-nitro-indirubinoxime, 5'-fluoro
      indirubinoxime, and 5'-trimethylacetamino-indirubinoxime were designed and tested
      for antitumor activity both in vitro and in vivo using rat tumor model.
      EXPERIMENTAL DESIGN: Three-week-old male Sprague-Dawley rats were inoculated s.c.
      on the left flank with 10(7) RK3E-ras rat kidney epithelial cells harboring k-ras
      gene. Alternatively, 5 x 10(6) RK3E-ras cells were injected into the oral mucosa.
      Indirubin derivative treatment began on the 3rd or 6th day after oral or s.c.
      cell injection, respectively. Indirubin derivatives were directly injected into
      the tumor every other day for a total of five times. Animals were monitored daily
      and tumor volume was measured by caliper. RESULTS: Indirubin derivatives showed
      potent antiproliferative activity on various human cancer cells and oncogenic
      RK3E-ras rat kidney cells, with IC(50) ranging from 1 to 12 mumol/L. Treatment
      with indirubin derivatives induced the activation of caspase-7 followed by
      apoptosis in RK3E-ras cells. Indirubin derivatives showed strong antitumor
      activity in rat solid and oral tumor models. Direct injection of indirubin
      derivatives every other day for 10 days induced significant inhibition of tumor
      growth in Sprague-Dawley rats bearing RK3E-ras-induced tumors. Histologically,
      treatment with indirubin derivatives caused significant inhibition of tumor
      formation with increased apoptosis and decreased tumor cell proliferation.
      CONCLUSIONS: Our data showed that novel indirubin derivatives 5'-nitro
      indirubinoxime, 5'-fluoro-indirubinoxime, and 5'-trimethylacetamino
      indirubinoxime effectively arrested the tumor growth by inhibiting cell
      proliferation and inducing apoptosis. These findings provide the potential value
      of indirubin derivatives as novel candidates for antitumor agents.

PMID- 17200362
TI  - Pilot study of rosiglitazone therapy in women with breast cancer: effects of
      short-term therapy on tumor tissue and serum markers.
AB  - PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a
      steroid nuclear receptor that is activated by natural compounds such as specific
      fatty acids and synthetic drugs such as thiazolidinedione antidiabetic agents.
      Expressed in normal and malignant mammary epithelial cells, activation of
      PPARgamma is associated with antiproliferative effects on human breast cancer
      cells in preclinical studies. The purpose of this study was to test the
      hypothesis that PPARgamma ligand therapy might inhibit tumor growth and
      progression in human breast cancer. EXPERIMENTAL DESIGN: We conducted a pilot
      trial of short-term (2-6 weeks) treatment with the thiazolidinedione
      rosiglitazone in 38 women with early-stage (T(is)-T(2), N(0-1), M(0)) breast
      cancer, administered between the time of diagnostic biopsy and definitive
      surgery. RESULTS: Short-term treatment with rosiglitazone (8 mg/d) did not elicit
      significant effects on breast tumor cell proliferation using Ki67 expression as a
      measure of cell proliferation and surrogate marker of tumor growth and
      progression. In pretreatment tumors notable for nuclear expression of PPARgamma
      by immunohistochemistry, down-regulation of nuclear PPARgamma expression occurred
      following rosiglitazone administration (P = 0.005). No PPARG mutations were
      identified, and the incidence of P12A and H446H polymorphisms did not differ
      relative to U.S. controls (P = 0.5). Treatment with rosiglitazone resulted in
      increased serum adiponectin (P < 0.001), decreased insulin levels (P = 0.005),
      and increased insulin sensitivity (P = 0.004). Rosiglitazone was well tolerated
      without serious adverse events. CONCLUSION: Our data indicate that short-term
      rosiglitazone therapy in early-stage breast cancer patients leads to local and
      systemic effects on PPARgamma signaling that may be relevant to breast cancer.

PMID- 17200364
TI  - Manipulation of base excision repair to sensitize ovarian cancer cells to
      alkylating agent temozolomide.
AB  - PURPOSE: To improve the treatment of women with ovarian cancer, we are
      investigating the modulation of a prominent DNA-damaging agent, temozolomide, by
      manipulating the DNA base excision repair (BER) pathway via BER inhibitor,
      methoxyamine, and overexpression of N-methylpurine DNA glycosylase (MPG).
      EXPERIMENTAL DESIGN: Enhancement of temozolomide via methoxyamine and MPG
      overexpression was analyzed using in vitro assays, including 3-(4-5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      salt (MTS) assay, apoptosis via Annexin staining, and Western blotting for H2AX
      phosphorylation to quantitate DNA damage. RESULTS: Our data show that we can
      effectively modulate the activity of the chemotherapeutic agent, temozolomide,
      via modulator methoxyamine, in three ovarian cancer cell lines, SKOV-3x, Ovcar-3,
      and IGROV-1. This enhancement of temozolomide-induced cytotoxicity is not
      dependent on p53 status as we transfected an ovarian cancer cell line with a
      dominant-negative p53-expressing plasmid (IGROV-1mp53) and obtained similar
      results. Our results show that MPG-overexpressing IGROV-1 and IGROV-1mp53 cells
      are significantly more sensitive to the clinical chemotherapeutic temozolomide in
      combination with methoxyamine as assayed by cytotoxicity, apoptosis, and levels
      of DNA damage than either agent alone. CONCLUSIONS: These studies show that
      although clinical trials in ovarian cancer to determine temozolomide single-agent
      efficacy are in development, through manipulation of the BER pathway, an increase
      in response to temozolomide is achieved. The combination of temozolomide plus
      methoxyamine has potential for second-line therapy for patients who have failed
      standard platinum plus paclitaxel chemotherapy.

PMID- 17200366
TI  - The effects of histone deacetylase inhibitors on the induction of differentiation
      in chondrosarcoma cells.
AB  - PURPOSE: Histologically, chondrosarcomas represent the degree of chondrogenic
      differentiation, which is associated with the prognosis of the disease. Histone
      acetylation and deacetylation play key roles in the regulation of chondrocytic
      differentiation. Here, we describe the antitumor effects of histone deacetylase
      (HDAC) inhibitors as differentiating reagents on chondrosarcomas. EXPERIMENTAL
      DESIGN: We examined the effects of a HDAC inhibitor, depsipeptide, on the growth
      of chondrosarcoma cell lines. We also investigated the modulation of the
      expression levels of extracellular matrix genes and the induction of phenotypic
      change in chondrosarcoma cells treated with depsipeptide. Finally, we examined
      the antitumor effect of depsipeptide on chondrosarcoma in vivo. RESULTS:
      Depsipeptide inhibited the growth of chondrosarcoma cells by inducing cell cycle
      arrest and/or apoptosis. HDAC inhibitors increased the expression of the alpha1
      chain of type II collagen (COL2A1) gene due to the enhanced histone acetylation
      in the promoter and enhancer. Depsipeptide also up-regulated the expressions of
      aggrecan and the alpha2 chain of type XI collagen (COL11A2) mRNA in a dose
      dependent manner. Moreover, long-term treatment with a low dose of depsipeptide
      resulted in the induction of differentiation into hypertrophic phenotype, as
      shown by the increment of the alpha1 chain of type X collagen (COL10A1)
      expression in chondrosarcoma cells. In vivo studies and histologic analyses
      confirmed that depsipeptide significantly inhibited tumor growth and induced
      differentiation into the hypertrophic and mineralized state in chondrosarcoma
      cells. CONCLUSIONS: These results strongly suggest that HDAC inhibitors may be
      promising reagents for use as a differentiating chemotherapy against
      chondrosarcomas.

PMID- 17200365
TI  - Inhibition of breast cancer cell growth in vitro and in vivo: effect of
      restoration of Wwox expression.
AB  - PURPOSE: The WWOX gene is down-regulated in breast cancer and loss of Wwox
      expression correlates with important clinical features of breast cancer. Thus, we
      have examined the effect of restoration of Wwox expression in breast cancer
      derived cells. EXPERIMENTAL DESIGN: Wwox protein expression was restored by the
      following: (a) infection with a recombinant adenovirus carrying WWOX cDNA (Ad
      WWOX) or (b) treatment with the DNA methyltransferase inhibitor, 5-aza-2'
      deoxycytidine, to activate the endogenous WWOX gene, in breast cancer-derived
      cells in vitro and in vivo. RESULTS: Restoration of Wwox expression led to
      suppression of growth of Wwox-deficient breast cancer-derived cells, through
      activation of the intrinsic caspase pathway, but did not affect growth of Wwox
      sufficient MCF7 cells. Intratumoral Wwox restoration, through Ad-WWOX infection
      or endogenous Wwox reactivation by 5-aza-2'-deoxycytidine injection, suppressed
      tumor growth in nude mice by inducing apoptosis. Alteration of global methylation
      levels was not observed. CONCLUSIONS: The results confirm that overexpression of
      exogenous Wwox inhibits breast cancer cell growth in vitro and in vivo and,
      perhaps more importantly, shows that restoration of endogenous Wwox expression,
      and likely other proteins, by treatment with a de novo methyltransferase
      inhibitor, also inhibits breast cancer cell growth and reverses breast cancer
      xenograft growth.

PMID- 17200368
TI  - Parathyroid hormone-related protein induces cachectic syndromes without directly
      modulating the expression of hypothalamic feeding-regulating peptides.
AB  - PURPOSE: Parathyroid hormone-related protein (PTHrP) is a causative factor of
      humoral hypercalcemia of malignancy (HHM) and concurrent anorexia and wasting.
      Because changes in the expression of hypothalamic feeding-regulating peptides can
      directly affect appetites and thereby can cause anorexia and wasting, we
      addressed whether the cachectic syndromes induced by PTHrP rely on the action of
      hypothalamic feeding-regulating peptides. EXPERIMENTAL DESIGN: Rats were
      inoculated with a LC-6 human cancer xenograft that secreted PTHrP, and the mRNA
      levels of the hypothalamic feeding-regulating peptide genes and serum leptin
      levels were examined before and after the development of HHM by in situ
      hybridization histochemistry and ELISA, respectively. Some rats were given the
      anti-PTHrP antibody. RESULTS AND CONCLUSION: The mRNA levels for the orexigenic
      peptides, such as the agouti-related protein and the neuropeptide Y in the
      arcuate nucleus (Arc), were significantly increased after the development of HHM,
      whereas the mRNA levels for the anorexigenic peptides, such as the
      proopiomelanocortin in the Arc, the cocaine and amphetamine-regulated transcript
      in the Arc, and the corticotropin-releasing factor in the paraventricular
      nucleus, were significantly decreased after the development of HHM. Plasma leptin
      levels were also reduced in cachectic rats, and the administration of anti-PTHrP
      antibody to the cachectic rats not only improved the cachectic symptoms but also
      restored the mRNA levels of these orexigenic and anorexigenic peptides, except
      for orexin. Thus, PTHrP induces HHM and concurrent cachectic syndromes by
      mechanisms other than directly modulating the leptin or hypothalamic feeding
      regulated peptides.

PMID- 17200367
TI  - Modifying dendritic cells via protein transfer for antitumor therapeutics.
AB  - PURPOSE: The modification of therapeutic dendritic cells (DC) with various
      immunostimulatory molecules represents a useful means for improving the antitumor
      efficacy of DC transfer-based immunotherapy. We have evaluated the feasibility of
      modifying therapeutic DCs with multiple immunostimulatory molecules using a time
      efficient, protein transfer (or protein "painting")-based method. EXPERIMENTAL
      DESIGN: Bone marrow-derived DCs were painted with either control protein human
      IgG (hIgG) or three immunostimulatory molecules, SLC, 4-1BBL, and TRANCE (the
      triad protein). Painted DCs were injected intratumorally into mice bearing
      established tumors. Subsequently, the capacities of painted DCs to migrate to the
      draining lymph nodes, recruit the host T cells, promote Th1 cytokine responses,
      and elicit therapeutic antitumor responses were evaluated. RESULTS: The triad
      protein transfer yields a uniform population of DCs that coexpress all three of
      the proteins. Compared with the hIgG-painted DCs, the triad protein-painted DCs
      migrate more efficiently to the draining lymph nodes and show enhanced
      capabilities to induce T cell infiltration of tumors and to promote Th1 cytokine
      responses in vivo. Furthermore, in both the EG.7 and TRAMP-C2 tumor models,
      compared with the DCs painted with hIgG or only one of the three proteins, the
      triad protein-painted DCs, upon adoptive transfer, elicit stronger therapeutic
      responses against established tumors. Importantly, the antitumor responses of the
      triad protein-painted DCs are mediated by systemic antitumor immunity.
      CONCLUSIONS: This study establishes, for the first time, the feasibility of
      optimizing DC transfer-based immunotherapy via combinatorial protein transfer of
      therapeutic DCs with an array of immunostimulatory molecules.

PMID- 17200369
TI  - Emerging role of platelet-derived growth factor receptor-beta inhibition in
      radioimmunotherapy of experimental pancreatic cancer.
AB  - PURPOSE: Thus far, the therapy of pancreatic cancer remains an insurmountable
      challenge. Not a solitary therapeutic modality in the battery of available
      therapeutic options is capable to cure or, at the very least, stop the
      progression of this disease in any meaningful way. The purpose of reported here
      studies was to implement a multimodality approach to radioimmunotherapy of
      pancreatic cancer and, ultimately, to develop a course of therapy with the
      clinical value. EXPERIMENTAL DESIGN: Animal model was NCr-nu/nu mouse bearing
      s.c. xenografts of SW1990 pancreatic adenocarcinoma. Radioimmunotherapy based on
      (131)ICC49, a TAG-72-targeting monoclonal antibody, was augmented with imatinib,
      a potent inhibitor of platelet-derived growth factor receptor-beta. The
      postulated interactions between these two modalities depended on the imatinib
      induced drop in the tumor interstitial fluid pressure and the subsequent increase
      of (131)ICC49 uptake into the tumor, resulting in improved tumor responses to
      radioimmunotherapy. RESULTS: Biodistribution studies revealed a 50% improvement
      in the tumor uptake of (131)ICC49 in mice treated with imatinib. Tumor
      development was practically arrested for approximately 3 weeks in response to the
      treatment composed of (131)ICC49 and imatinib with tumor quadrupling time (T(Q))
      of 40.8 days. (131)ICC49 alone and imatinib alone also delayed the tumor growth
      to T(Q) of 30.2 and 31.2 days, respectively. Unanticipated was the significant
      response of SW1990 to a brief treatment with imatinib given i.p. at 100 mg/kg
      b.i.d. for 3 days. Xenografts in control mice receiving injection of PBS had T(Q)
      of 23 days. CONCLUSIONS: The inclusion of imatinib in the radioimmunotherapy
      regimen is beneficial and it does not produce any overt side effects. The
      improved responses of pancreatic cancer xenografts to the multimodality treatment
      comprising radioimmunotherapy and platelet-derived growth factor receptor-beta
      inhibition suggest that this approach to therapy of pancreatic cancer may also be
      successful in patients.

PMID- 17200370
TI  - Virotherapy with a type 2 herpes simplex virus-derived oncolytic virus induces
      potent antitumor immunity against neuroblastoma.
AB  - PURPOSE: We recently constructed an oncolytic virus from type 2 herpes simplex
      virus (HSV-2) that selectively targets and kills tumor cells with an activated
      Ras signaling pathway. Designated FusOn-H2, this virus has shown several discrete
      killing mechanisms. Here, we evaluated the antitumor immune responses after FusOn
      H2-mediated virotherapy in a syngeneic murine neuroblastoma model. EXPERIMENTAL
      DESIGN: We directly injected FusOn-H2 into established tumors and then measured
      its antitumor effect and the accompanying tumor-specific immune responses.
      Several oncolytic HSVs constructed from HSV-1 were included in the same
      experiments for comparisons. RESULTS: Our data show that tumor destruction by
      FusOn-H2 in vivo induces potent antitumor immune responses in this syngeneic
      neuroblastoma model. The elicited cellular immunity not only eradicated
      neuroblastoma cells in vitro but also inhibited the growth of tumors at sites
      distant from the virus injection site. Moreover, adoptive transfer of splenocytes
      from mice receiving virotherapy to naive mice resulted in a measurable antitumor
      effect. CONCLUSION: We conclude that the ability of FusOn-H2 to induce tumor
      specific cellular immunity expands the oncolytic repertoire of this virus and
      increases the likelihood that its use in patients would produce significant
      therapeutic benefits.

PMID- 17200371
TI  - Monitoring response to anticancer therapy by targeting microbubbles to tumor
      vasculature.
AB  - PURPOSE: New strategies to detect tumor angiogenesis and monitor response of
      tumor vasculature to therapy are needed. Contrast ultrasound imaging using
      microbubbles targeted to tumor endothelium offers a noninvasive method for
      monitoring and quantifying vascular effects of antitumor therapy. We investigated
      the use of targeted microbubbles to follow vascular response of therapy in a
      mouse model of pancreatic adenocarcinoma. EXPERIMENTAL DESIGN: Microbubbles
      conjugated to monoclonal antibodies were used to image and quantify vascular
      effects of two different antitumor therapies in s.c. and orthotopic pancreatic
      tumors in mice. Tumor-bearing mice were treated with anti-vascular endothelial
      growth factor (VEGF) monoclonal antibodies and/or gemcitabine, and the
      localization of microbubbles to endoglin (CD105), VEGF receptor 2 (VEGFR2), or
      VEGF-activated blood vessels (the VEGF-VEGFR complex) was monitored by contrast
      ultrasound. RESULTS: Targeted microbubbles showed significant enhancement of
      tumor vasculature when compared with untargeted or control IgG-targeted
      microbubbles. Video intensity from targeted microbubbles correlated with the
      level of expression of the target (CD105, VEGFR2, or the VEGF-VEGFR complex) and
      with microvessel density in tumors under antiangiogenic or cytotoxic therapy.
      CONCLUSIONS: We conclude that targeted microbubbles represent a novel and
      attractive tool for noninvasive, vascular-targeted molecular imaging of tumor
      angiogenesis and for monitoring vascular effects specific to antitumor therapy in
      vivo.

PMID- 17200373
TI  - Therapeutic synergy of human papillomavirus E7 subunit vaccines plus cisplatin in
      an animal tumor model: causal involvement of increased sensitivity of cisplatin
      treated tumors to CTL-mediated killing in therapeutic synergy.
AB  - PURPOSE: The goal of this study was to investigate the therapeutic potentials of
      combining chemotherapy with human papillomavirus (HPV) E7 subunit vaccines in an
      animal tumor model and to determine the underlying therapeutic mechanisms.
      EXPERIMENTAL DESIGN: Animals bearing HPV E6/E7-expressing tumors were treated
      intratumorally with a selected cytotoxic drug, cisplatin, twice at 1-week
      interval and s.c. with E7 subunit vaccines thrice at 1-week interval. Tumor
      chemoimmunoresponse was measured by tumor size. Ag-specific CTL activities and
      tumor histology were checked in mice under treatments. Apoptosis, in vivo T-cell
      subset depletion, adoptive CTL transfer, and tumor regression were used to
      determine the mechanisms for antitumor therapeutic effects. RESULTS: Combined
      therapy using cisplatin plus E7 subunit vaccines improved cure and recurrence
      rates of tumors and long-term antitumor immunity dramatically more than single
      therapy alone. In particular, both components of E7 subunit vaccines were
      required for induction of Ag-specific CTL as well as therapeutic synergy when
      combined with cisplatin. This therapeutic synergy was abrogated by depletion of
      CD8(+) T cells in vivo and was concomitant with histologic changes (such as heavy
      infiltration of lymphocytes and reduced tumor cell density). Finally, the
      increased sensitivity of cisplatin-treated tumors to CTL-mediated killing was
      found to be responsible for therapeutic synergy. CONCLUSIONS: E7 subunit vaccines
      plus cisplatin mediate antitumor therapeutic synergy through the increased
      sensitivity of cisplatin-treated tumors to CTL-mediated killing. Moreover, E7
      based therapeutic vaccines have the potential to improve chemotherapy in patients
      with cervical cancer.

PMID- 17200372
TI  - The combi-targeting concept: in vitro and in vivo fragmentation of a stable combi
      nitrosourea engineered to interact with the epidermal growth factor receptor
      while remaining DNA reactive.
AB  - PURPOSE: JDA58 (NSC 741282), a "combi-molecule" optimized in the context of the
      "combi-targeting concept," is a nitrosourea moiety tethered to an
      anilinoquinazoline. Here, we sought to show its binary epidermal growth factor
      receptor (EGFR)/DNA targeting property and to study its fragmentation in vitro
      and in vivo. EXPERIMENTAL DESIGN: The fragmentation of JDA58 was detected in
      cells in vitro and in vivo by fluorescence microscopy and tandem mass
      spectrometry. EGFR phosphorylation and DNA damage were determined by Western
      blotting and comet assay, respectively. Tumor data were examined for statistical
      significance using the Student's t test. RESULTS: JDA58 inhibited EGFR tyrosine
      kinase (IC(50), 0.2 micromol/L) and blocked EGFR phosphorylation in human DU145
      prostate cancer cells. It induced significant levels of DNA damage in DU145 cells
      in vitro or in vivo and showed potent antiproliferative activity both in vitro
      and in a DU145 xenograft model. In cell-free medium, JDA58 was hydrolyzed to
      JDA35, a fluorescent amine that could be observed in tumor cells both in vitro
      and in vivo. In tumor cells in vitro or in vivo, or in plasma collected from
      mice, the denitrosated species JDA41 was the predominant metabolite. However,
      mass spectrometric analysis revealed detectable levels of the hydrolytic product
      JDA35 in tumor cells both in vitro and in vivo. CONCLUSIONS: The results in toto
      suggest that growth inhibition in vitro and in vivo may be sustained by the
      intact combi-molecule plus JDA35 plus JDA41, three inhibitors of EGFR, and the
      concomitantly released DNA-damaging species. This leads to a model wherein a
      single molecule carries a complex multitargeted-multidrug combination.

PMID- 17200374
TI  - Pterostilbene, an active constituent of blueberries, suppresses aberrant crypt
      foci formation in the azoxymethane-induced colon carcinogenesis model in rats.
AB  - PURPOSE: Epidemiologic studies have linked the consumption of fruits and
      vegetables to reduced risk of several types of cancer. Laboratory animal model
      studies have provided evidence that stilbenes, phenolic compounds present in
      grapes and blueberries, play a role in inhibiting the risk of certain cancers.
      Pterostilbene, a naturally occurring stilbene from blueberries, was tested for
      its preventive activity against colon carcinogenesis. EXPERIMENTAL DESIGN:
      Experiments were designed to study the inhibitory effect of pterostilbene against
      the formation of azoxymethane-induced colonic aberrant crypt foci (ACF)
      preneoplastic lesions in male F344 rats. Beginning at 7 weeks of age, rats were
      treated with azoxymethane (15 mg/kg body weight s.c., once weekly for 2 weeks).
      One day after the second azoxymethane treatment, rats were fed experimental diets
      containing 0 or 40 ppm of pterostilbene. At 8 weeks after the second azoxymethane
      treatment, all rats were sacrificed, and colons were evaluated for ACF formation
      and for inhibition of inducible nitric oxide synthase (iNOS) and proliferating
      cell nuclear antigen. Effects on mucin MUC2 were also determined. RESULTS:
      Administration of pterostilbene for 8 weeks significantly suppressed azoxymethane
      induced formation of ACF (57% inhibition, P < 0.001) and multiple clusters of
      aberrant crypts (29% inhibition, P < 0.01). Importantly, dietary pterostilbene
      also suppressed azoxymethane-induced colonic cell proliferation and iNOS
      expression. Inhibition of iNOS expression by pterostilbene was confirmed in
      cultured human colon cancer cells. CONCLUSIONS: The results of the present study
      suggest that pterostilbene, a compound present in blueberries, is of great
      interest for the prevention of colon cancer.

PMID- 17200375
TI  - Explaining the familial colorectal cancer risk associated with mismatch repair
      (MMR)-deficient and MMR-stable tumors.
AB  - PURPOSE: There is a paucity of data quantifying the familial risk of colorectal
      cancer associated with mismatch repair (MMR)-deficient and MMR-stable tumors. To
      address this, we analyzed a population-based series of 1,042 colorectal cancer
      probands with verified family histories. EXPERIMENTAL DESIGN: Constitutional DNA
      from probands was systematically screened for MYH variants and those with cancers
      displaying microsatellite instability (MSI) for germ-line MMR mutations;
      diagnoses of familial adenomatous polyposis and juvenile polyposis were
      established based on clinical phenotype and mutational analysis. Familial
      colorectal cancer risks were enumerated from age-, sex-, and calendar-specific
      population incidence rates. Segregation analysis was conducted to derive a model
      of the residual familial aggregation of colorectal cancer. RESULTS: Germ-line
      predisposition to colorectal cancer was identified in 37 probands [3.4%; 95%
      confidence interval (95% CI), 2.4-4.6]: 29 with MLH1/MSH2 mutations, 2 with
      familial adenomatous polyposis, 1 with juvenile polyposis, and 5 with biallelic
      MYH variants. The risk of colorectal cancer in first-degree relatives of probands
      with MSI and MMR-stable cancers was increased 5.01-fold (95% CI, 3.73-6.59) and
      1.31-fold (95% CI, 1.07-1.59), respectively. MSH2/MLH1 mutations were responsible
      for 50% of the overall excess familial risk and 80% of the risk associated with
      MSI cancers but 32% of the familial risk was unaccounted for by known loci.
      Genetic models based on major gene loci did not provide a better explanation of
      the residual familial aggregation than a simple polygenic model. CONCLUSIONS: The
      information from our analyses should be useful in quantifying familial risks in
      clinical practice and in the design of studies to identify novel disease alleles.

PMID- 17200376
TI  - CanWest set to challenge ban on DTCA.

PMID- 17200377
TI  - New Liberal leader champions R&D boost.

PMID- 17200378
TI  - Quebec allows Vioxx class-action suit.

PMID- 17200379
TI  - Furor over proposed offshore teleradiology.

PMID- 17200380
TI  - Auditor-General slams regulatory regime.

PMID- 17200381
TI  - Plans afoot for national network of for-profit urgent care centres.

PMID- 17200382
TI  - Ottawa creates clearing house for cancer information.

PMID- 17200384
TI  - International aid doldrums.

PMID- 17200383
TI  - Prominent researcher is CMAJ's new editor-in-chief.

PMID- 17200385
TI  - The rash of secondary syphilis.

PMID- 17200386
TI  - Canada's public health system: building support for front-line physicians.

PMID- 17200387
TI  - Paraesophageal hernia.

PMID- 17200388
TI  - Lambert-Eaton myasthenic syndrome.

PMID- 17200389
TI  - Reliability of disclosure forms of authors' contributions.
AB  - BACKGROUND: The contribution disclosure forms used by medical journals to assess
      and confirm authorship are surveys of self-reported behaviour that follow the
      cognitive rules of psychometric instruments. We sought to analyze how
      autobiographical memory, defined as memory for events and issues related to
      oneself, affected the reliability of contribution forms for the judging of
      authorship of research articles. METHODS: We conducted a prospective study, which
      ultimately included 919 authors of 201 articles submitted to a general medical
      journal from July 2001 through December 2002. A authorship disclosure form with a
      checklist of 11 possible contribution choices for all authors was sent first to
      each article's corresponding author, who was asked to fill it out for all
      authors. A blank form was then sent to each author individually to disclose his
      or her own contribution to that article. The main outcome measure was test-
      retest differences between the corresponding authors' self-declarations,
      expressed in percent as the gross difference rate (GDR) for each article.
      RESULTS: More than two-thirds of the corresponding authors (69.7%) differed in at
      least 1 contribution choice between the 2 disclosure statements made about their
      own contributions. The reliability of their answers was low to moderate (GDRs >
      10%), especially for contributions on the provision of study materials or
      patients or final approval of the article (GDR 22.9%), guarantor of the study
      (GDR 20.9%) and drafting of the manuscript (GDR 20.4%). As a proxy for their
      coauthors' contributions, corresponding authors also differed from them in the
      perception of noncorresponding authors' contributions, disagreeing in 69.4% of
      cases. Of the 718 noncorresponding authors, 204 (28.4%) met all the criteria for
      authorship set out by the International Committee of Medical Journal Editors
      according to the statement given by the corresponding author. When they described
      their own contributions, this prevalence increased to 40.5%. INTERPRETATION:
      Psychological factors such as autobiographical memory may confound contribution
      disclosures as an evaluation tool for authorship on scientific articles and
      affect responsible authorship and publication practices.

PMID- 17200392
TI  - For-profit versus not-for-profit delivery of long-term care.

PMID- 17200390
TI  - Protective measures and human antibody response during an avian influenza H7N3
      outbreak in poultry in British Columbia, Canada.
AB  - BACKGROUND: In 2004 an outbreak of avian influenza of the H7N3 subtype occurred
      among poultry in British Columbia, Canada. We report compliance with recommended
      protective measures and associated human infections during this outbreak.
      METHODS: We sought voluntary participation by anyone (cullers, farmers and their
      families) involved in efforts to control the poultry outbreak. Recruitment was by
      advertisements at the worker deployment site, in local media and through
      newsletters sent directly to farmers. Sera were tested for antibody to H7N3 by
      microneutralization assay. A subset of 16 sera (including convalescent sera from
      2 unprotected workers with conjunctivitis from whom virus had been isolated) was
      further tested by Western blot and routine and modified hemagglutination
      inhibition assays. RESULTS: A total of 167 people (20% to 25% of all workers)
      participated between May 7 and July 26, 2004. Of these, 19 had experienced
      influenza-like illness and 21 had experienced red or watery eyes. There was no
      significant association between illness reports and exposure to infected birds.
      Among 65 people who entered barns with infected birds, 55 (85%) had received
      influenza vaccine, 48 (74%) had received oseltamivir, and 55 (85%), 54 (83%) and
      36 (55%) reported always wearing gloves, mask or goggles, respectively. Antibody
      to the H7 subtype was not detected in any sera. INTERPRETATION: During the BC
      outbreak, compliance with recommended protective measures, especially goggles,
      was incomplete. Multiple back-up precautions, including oseltamivir prophylaxis,
      may prevent human infections and should be readily accessible and consistently
      used by those involved in the control of future outbreaks of avian influenza in
      poultry. Localized human avian influenza infections may not result in serologic
      response despite confirmed viral detection and culture.

PMID- 17200391
TI  - Community-associated MRSA: superbug at our doorstep.

PMID- 17200393
TI  - Lead and mercury exposures: interpretation and action.
AB  - Lead and mercury are naturally occurring elements in the earth's crust and are
      common environmental contaminants. Because people concerned about possible
      exposures to these elements often seek advice from their physicians, clinicians
      need to be aware of the signs and symptoms of lead and mercury poisoning, how to
      investigate a possible exposure and when intervention is necessary. We describe 3
      cases of patients who presented to an occupational medicine specialist with
      concerns of heavy metal toxicity. We use these cases to illustrate some of the
      issues surrounding the investigation of possible lead and mercury exposures. We
      review the common sources of exposure, the signs and symptoms of lead and mercury
      poisoning and the appropriate use of chelation therapy. There is a need for a
      clear and consistent guide to help clinicians interpret laboratory
      investigations. We offer such a guide, with information about population norms,
      lead and mercury levels that suggest exposure beyond that seen in the general
      population and levels that warrant referral for advice about clinical management.

PMID- 17200394
TI  - Obesity registers.

PMID- 17200395
TI  - [Malnutrition in developing countries].

PMID- 17200397
TI  - Safe prescribing.

PMID- 17200398
TI  - Do you really know how tall you are?

PMID- 17200399
TI  - Preventing adverse drug events.

PMID- 17200400
TI  - Prescribing powers for pharmacists.

PMID- 17200402
TI  - Training Canada's future clinician-teachers and researchers.

PMID- 17200403
TI  - Novel technique for critical care training.

PMID- 17200404
TI  - Registration requirements.

PMID- 17200405
TI  - Canadian mnemonics for heart sounds.

PMID- 17200406
TI  - Free access to medical information: a moral right?

PMID- 17200408
TI  - Enhanced mast cell activation in mice deficient in the A2b adenosine receptor.
AB  - Antigen-mediated cross-linking of IgE bound to mast cells via the high affinity
      receptor for IgE triggers a signaling cascade that results in the release of
      intracellular calcium stores, followed by an influx of extracellular calcium. The
      collective increase in intracellular calcium is critical to the release of the
      granular contents of the mast cell, which include the mediators of acute
      anaphylaxis. We show that the sensitivity of the mast cell to antigen-mediated
      degranulation through this pathway can be dramatically influenced by the A2b
      adenosine receptor. Loss of this Gs-coupled receptor on mouse bone marrow-derived
      mast cells results in decreased basal levels of cyclic AMP and an excessive
      influx of extracellular calcium through store-operated calcium channels following
      antigen activation. Mice lacking the A2b receptor display increased sensitivity
      to IgE-mediated anaphylaxis. Collectively, these findings show that the A2b
      adenosine receptor functions as a critical regulator of signaling pathways within
      the mast cell, which act in concert to limit the magnitude of mast cell
      responsiveness when antigen is encountered.

PMID- 17200409
TI  - Anti-TNF-alpha therapy induces a distinct regulatory T cell population in
      patients with rheumatoid arthritis via TGF-beta.
AB  - The induction of regulatory T (T reg) cells holds considerable potential as a
      treatment for autoimmune diseases. We have previously shown that CD4+CD25hi T reg
      cells isolated from patients with active rheumatoid arthritis (RA) have a defect
      in their ability to suppress proinflammatory cytokine production by CD4+CD25-
      [corrected] T cells. This defect, however, was overcome after anti-tumor necrosis
      factor (TNF)-alpha antibody (infliximab) therapy. Here, we demonstrate that
      infliximab therapy gives rise to a CD4+CD25hiFoxP3+ T reg cell population, which
      mediates suppression via transforming growth factor (TGF)-beta and interleukin
      10, and lacks CD62L expression, thereby distinguishing this T reg cell subset
      from natural T reg cells present in healthy individuals and patients with active
      RA. In vitro, infliximab induced the differentiation of CD62L- T reg cells from
      CD4+CD25- T cells isolated from active RA patients, a process dependent on TGF
      beta. In spite of the potent suppressor capacity displayed by this CD62L- T reg
      cell population, the natural CD62L+ T reg cells remained defective in infliximab
      treated patients. These results suggest that anti-TNF-alpha therapy in RA
      patients generates a newly differentiated population of T reg cells, which
      compensates for the defective natural T reg cells. Therefore, manipulation of a
      proinflammatory environment could represent a therapeutic strategy for the
      induction of T reg cells and the restoration of tolerance.

PMID- 17200410
TI  - Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by
      inducible costimulator ligand.
AB  - Although there is evidence for distinct roles of myeloid dendritic cells (DCs
      [mDCs]) and plasmacytoid pre-DCs (pDCs) in regulating T cell-mediated adaptive
      immunity, the concept of functional DC subsets has been questioned because of the
      lack of a molecular mechanism to explain these differences. In this study, we
      provide direct evidence that maturing mDCs and pDCs express different sets of
      molecules for T cell priming. Although both maturing mDCs and pDCs upregulate the
      expression of CD80 and CD86, only pDCs upregulate the expression of inducible
      costimulator ligand (ICOS-L) and maintain high expression levels upon
      differentiation into mature DCs. High ICOS-L expression endows maturing pDCs with
      the ability to induce the differentiation of naive CD4 T cells to produce
      interleukin-10 (IL-10) but not the T helper (Th)2 cytokines IL-4, -5, and -13.
      These IL-10-producing T cells are T regulatory cells, and their generation by
      ICOS-L is independent of pDC-driven Th1 and Th2 differentiation, although, in the
      later condition, some contribution from endogenous IL-4 cannot be completely
      ruled out. Thus, in contrast to mDCs, pDCs are poised to express ICOS-L upon
      maturation, which leads to the generation of IL-10-producing T regulatory cells.
      Our findings demonstrate that mDC and pDCs are intrinsically different in the
      expression of costimulatory molecules that drive distinct types of T cell
      responses.

PMID- 17200411
TI  - IL-25 regulates Th17 function in autoimmune inflammation.
AB  - Interleukin (IL)-25 is a member of the IL-17 family of cytokines. However, unlike
      the other members of this family, IL-25 promotes T helper (Th) 2 responses. We
      now show that IL-25 also regulates the development of autoimmune inflammation
      mediated by IL-17-producing T cells. We have generated IL-25-deficient (il25-/-)
      mice and found that they are highly susceptible to experimental autoimmune
      encephalomyelitis (EAE). The accelerated disease in the il25-/- mice is
      associated with an increase of IL-23 in the periphery and a subsequent increase
      in the number of inflammatory IL-17-, IFNgamma-, and TNF-producing T cells that
      invade the central nervous system. Neutralization of IL-17 but not IFNgamma in
      il25-/- mice prevented EAE, suggesting that IL-17 is a major disease-promoting
      factor. IL-25 treatment at several time points during a relapse-remitting model
      or chronic model of EAE completely suppressed disease. IL-25 treatment induced
      elevated production of IL-13, which is required for suppression of Th17 responses
      by direct inhibition of IL-23, IL-1beta, and IL-6 expression in activated
      dendritic cells. Thus, IL-25 and IL-17, being members of the same cytokine
      family, play opposing roles in the pathogenesis of organ-specific autoimmunity.

PMID- 17200412
TI  - Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease.
AB  - The scurfy mutant mouse strain suffers from a fatal lymphoproliferative disease
      leading to early death within 3-4 wk of age. A frame-shift mutation of the
      forkhead box transcription factor Foxp3 has been identified as the molecular
      cause of this multiorgan autoimmune disease. Foxp3 is a central control element
      in the development and function of regulatory T cells (T reg cells), which are
      necessary for the maintenance of self-tolerance. However, it is unclear whether
      dysfunction or a lack of T reg cells is etiologically involved in scurfy
      pathogenesis and its human correlate, the IPEX syndrome. We describe the
      generation of bacterial artificial chromosome-transgenic mice termed "depletion
      of regulatory T cell" (DEREG) mice expressing a diphtheria toxin (DT) receptor
      enhanced green fluorescent protein fusion protein under the control of the foxp3
      gene locus, allowing selective and efficient depletion of Foxp3+ T reg cells by
      DT injection. Ablation of Foxp3+ T reg cells in newborn DEREG mice led to the
      development of scurfy-like symptoms with splenomegaly, lymphadenopathy,
      insulitis, and severe skin inflammation. Thus, these data provide experimental
      evidence that the absence of Foxp3+ T reg cells is indeed sufficient to induce a
      scurfy-like phenotype. Furthermore, DEREG mice will allow a more precise
      definition of the function of Foxp3+ T reg cells in immune reactions in vivo.

PMID- 17200413
TI  - Jump-starting kinesin.
AB  - When it is not actively transporting cargo, conventional Kinesin-1 is present in
      the cytoplasm in a folded conformation that cannot interact effectively with
      microtubules (MTs). Two important and largely unexplored aspects of kinesin
      regulation are how it is converted to an active species when bound to cargo and
      the related issue of how kinesin discriminates among its many potential cargo
      molecules. Blasius et al. (see p. 11 of this issue) report that either binding of
      the cargo linker c-Jun N-terminal kinase-interacting protein 1 (JIP1) to the
      light chains (LCs) or binding of fasciculation and elongation protein zeta1
      (FEZ1) to the heavy chains (HCs) is insufficient for activation but that
      activation occurs when both are present simultaneously. A related paper by Cai et
      al. (see p. 51 of this issue) provides structural insight into the conformation
      of the folded state in the cell obtained by fluorescence resonance energy
      transfer analysis.

PMID- 17200414
TI  - Two binding partners cooperate to activate the molecular motor Kinesin-1.
AB  - The regulation of molecular motors is an important cellular problem, as motility
      in the absence of cargo results in futile adenosine triphosphate hydrolysis. When
      not transporting cargo, the microtubule (MT)-based motor Kinesin-1 is kept
      inactive as a result of a folded conformation that allows autoinhibition of the N
      terminal motor by the C-terminal tail. The simplest model of Kinesin-1 activation
      posits that cargo binding to nonmotor regions relieves autoinhibition. In this
      study, we show that binding of the c-Jun N-terminal kinase-interacting protein 1
      (JIP1) cargo protein is not sufficient to activate Kinesin-1. Because two regions
      of the Kinesin-1 tail are required for autoinhibition, we searched for a second
      molecule that contributes to activation of the motor. We identified fasciculation
      and elongation protein zeta1 (FEZ1) as a binding partner of kinesin heavy chain.
      We show that binding of JIP1 and FEZ1 to Kinesin-1 is sufficient to activate the
      motor for MT binding and motility. These results provide the first demonstration
      of the activation of a MT-based motor by cellular binding partners.

PMID- 17200415
TI  - Two distinct modes of myosin assembly and dynamics during epithelial wound
      closure.
AB  - Actomyosin contraction powers the sealing of epithelial sheets during
      embryogenesis and wound closure; however, the mechanisms are poorly understood.
      After laser ablation wounding of Madin-Darby canine kidney cell monolayers, we
      observed distinct steps in wound closure from time-lapse images of myosin
      distribution during resealing. Immediately upon wounding, actin and myosin II
      regulatory light chain accumulated at two locations: (1) in a ring adjacent to
      the tight junction that circumscribed the wound and (2) in fibers at the base of
      the cell in membranes extending over the wound site. Rho-kinase activity was
      required for assembly of the myosin ring, and myosin II activity was required for
      contraction but not for basal membrane extension. As it contracted, the myosin
      ring moved toward the basal membrane with ZO-1 and Rho-kinase. Thus, we suggest
      that tight junctions serve as attachment points for the actomyosin ring during
      wound closure and that Rho-kinase is required for localization and activation of
      the contractile ring.

PMID- 17200416
TI  - Kinesin-1 structural organization and conformational changes revealed by FRET
      stoichiometry in live cells.
AB  - Kinesin motor proteins drive the transport of cellular cargoes along microtubule
      tracks. How motor protein activity is controlled in cells is unresolved, but it
      is likely coupled to changes in protein conformation and cargo association. By
      applying the quantitative method fluorescence resonance energy transfer (FRET)
      stoichiometry to fluorescent protein (FP)-labeled kinesin heavy chain (KHC) and
      kinesin light chain (KLC) subunits in live cells, we studied the overall
      structural organization and conformation of Kinesin-1 in the active and inactive
      states. Inactive Kinesin-1 molecules are folded and autoinhibited such that the
      KHC tail blocks the initial interaction of the KHC motor with the microtubule. In
      addition, in the inactive state, the KHC motor domains are pushed apart by the
      KLC subunit. Thus, FRET stoichiometry reveals conformational changes of a protein
      complex in live cells. For Kinesin-1, activation requires a global conformational
      change that separates the KHC motor and tail domains and a local conformational
      change that moves the KHC motor domains closer together.

PMID- 17200417
TI  - Spatial targeting of type II protein kinase A to filopodia mediates the
      regulation of growth cone guidance by cAMP.
AB  - The second messenger cyclic adenosine monophosphate (cAMP) plays a pivotal role
      in axonal growth and guidance, but its downstream mechanisms remain elusive. In
      this study, we report that type II protein kinase A (PKA) is highly enriched in
      growth cone filopodia, and this spatial localization enables the coupling of cAMP
      signaling to its specific effectors to regulate guidance responses. Disrupting
      the localization of PKA to filopodia impairs cAMP-mediated growth cone attraction
      and prevents the switching of repulsive responses to attraction by elevated cAMP.
      Our data further show that PKA targets protein phosphatase-1 (PP1) through the
      phosphorylation of a regulatory protein inhibitor-1 (I-1) to promote growth cone
      attraction. Finally, we find that I-1 and PP1 mediate growth cone repulsion
      induced by myelin-associated glycoprotein. These findings demonstrate that the
      spatial localization of type II PKA to growth cone filopodia plays an important
      role in the regulation of growth cone motility and guidance by cAMP.

PMID- 17200418
TI  - Conjugated bile acids regulate hepatocyte glycogen synthase activity in vitro and
      in vivo via Galphai signaling.
AB  - The regulation of glycogen synthase activity by bile acids in primary hepatocytes
      and in the intact liver was investigated. Bile acids (deoxycholic acid, DCA;
      taurocholic acid, TCA) activated AKT and glycogen synthase (GS) in primary rat
      hepatocytes. Incubation with a phosphatidyl inositol-3 kinase inhibitor or
      expression of dominant-negative AKT in primary rat hepatocytes abolished
      activation of AKT and GS by DCA and TCA. TCA, but not DCA, activated Galpha(i)
      proteins in primary rat hepatocytes. Treatment of cells with pertussis toxin or
      expression of dominant-negative Galpha(i) blocked TCA-induced activation of AKT
      and of GS but did not alter AKT or GS activation caused by DCA. TCA caused
      activation of AKT and GS in intact rat liver. Expression of dominant-negative
      Galpha(i) reduced TCA-induced activation of AKT and of GS in intact rat liver.
      Together, our findings demonstrate that bile acids are physiological regulators
      of glycogen synthase in rat liver and that conjugated bile acids use a Galpha(i)
      coupled G protein-coupled receptor to regulate GS activity in vitro and in vivo.

PMID- 17200419
TI  - Uncovering the pharmacology of the G protein-coupled receptor GPR40: high
      apparent constitutive activity in guanosine 5'-O-(3-[35S]thio)triphosphate
      binding studies reflects binding of an endogenous agonist.
AB  - In cells lacking expression of Ca(2+)-mobilizing G proteins, coexpression of
      human GPR40 and Galpha(q) allowed medium- and long-chain fatty acids to elevate
      intracellular [Ca(2+)]. This was also observed when human embryonic kidney (HEK)
      293 cells were transfected with a GPR40-Galpha(q) fusion protein. The kinetic of
      elevation of intracellular [Ca(2+)] slowed with increasing fatty acid chain
      length, suggesting different ligand on-rates, whereas the addition of fatty acid
      free bovine serum albumin reduced signals, presumably by binding the fatty acids.
      To allow effective ligand equilibration, GPR40-Galpha(q) was used in guanosine 5'
      O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding assays. After expression
      of GPR40-Galpha(q) in HEK293 cells and membrane preparation basal binding of
      [(35)S]GTPgammaSinGalpha(q) immunoprecipitates was high and not elevated
      substantially by fatty acids. However, treatment of membranes with fatty acid
      free bovine serum albumin reduced the basal [(35)S]GTPgammaS binding in a
      concentration-dependent manner and allowed the responsiveness and pharmacology at
      GPR40 of each of the fatty acids thiazolidinediones and a novel small-molecule
      agonist to be uncovered. Membranes of rat INS-1E cells that express GPR40
      endogenously provided similar observations. The high apparent constitutive
      activity of GPR40-Galpha(q) was also reversed by a small-molecule GPR40
      antagonist, and basal [(35)S]GTPgammaS binding was prevented by the selective
      Galpha(q)/Galpha(11) inhibitor YM-254890. The current studies provide novel
      insights into the pharmacology of GPR40 and indicate that G protein-coupled
      receptors which respond to fatty acids, and potentially to other lipid ligands,
      can be occupied by endogenous agonists before assay and that this may mask the
      pharmacology of the receptor and may be mistaken for high levels of constitutive
      activity.

PMID- 17200420
TI  - flp gene disruption in a parasitic nematode reveals motor dysfunction and unusual
      neuronal sensitivity to RNA interference.
AB  - The potato cyst nematode Globodera pallida is a serious pest of potato crops.
      Nematode FMRFamide-like peptides (FLPs) are one of the most diverse neuropeptide
      families known, and modulate sensory and motor functions. As neuromuscular
      function is a well-established target for parasite control, parasitic nematode
      FLP signaling has significant potential in novel control strategies. In the
      absence of transgenic parasitic nematodes and the reported ineffectiveness of
      neuronal gene RNAi in Caenorhabditis elegans, nothing is known about flp function
      in nematode parasites. In attempts to evaluate flp function in G. pallida, we
      have discovered that, unlike in C. elegans, these genes are readily susceptible
      to RNAi. Silencing any of the five characterized G. pallida flp genes (Gp-flp-1, 
      6, -12, -14, or -18) incurred distinct aberrant behavioral phenotypes consistent
      with key roles in motor function. Further delineation of these effects revealed
      that double-stranded RNA exposure time (> or = 18 h) and concentration (> or =
      0.1 microg/ml) were critical to the observed effects, which were reversible. G.
      pallida flp genes are essential to coordinated locomotory activities, do not
      display redundancy, and are susceptible to RNAi, paving the way for the
      investigation of RNAi-mediated flp gene silencing as a novel plant parasite
      control strategy.

PMID- 17200421
TI  - NASA--has its biological groundwork for a trip to Mars improved?
AB  - In a 1991 editorial in The FASEB Journal, Robert W. Krauss commented on a recent
      report of the Presidential Advisory Committee on the Future of the U.S. Space
      Program (Augustine report). He concluded that, although a manned mission to Mars
      with life sciences as the priority was endorsed by the Committee, it failed to
      deal realistically with one huge gap; biological sciences have never been given
      high priority. According to Krauss, this left a void that will cripple, perhaps
      fatally, any early effort to ensure long-term survival on any mission of extended
      duration. The gap included insufficient flight time for fundamental biological
      space research and insufficient funds. Krauss expressed his opinions 15 years
      ago. Have we better knowledge of space biology now? This question becomes more
      acute now that President George W. Bush recently proposed a manned return to the
      moon by 2015 or 2020, with the moon to become our staging post for manned
      missions to Mars. Will we be ready so soon? A review of the progress in the last
      15 years suggests that we will not. Because of the Columbia disaster, flight
      opportunities for biological sciences in shuttle spacelabs and in Space Station
      laboratories compete with time for engineering problems and construction. Thus,
      research on gravity, radiation, and isolation loses out to problems deemed to be
      of higher priority. Radiation in deep space and graded gravity in space with on
      board centrifuges are areas that must be studied before we undertake prolonged
      space voyages. Very recent budgetary changes within National Aeronautics and
      Space Administration threaten to greatly reduce the fundamental space biology
      funds. Are we ready for a trip to Mars? Like Krauss 15 years ago, I think not for
      some time.

PMID- 17200423
TI  - Evolvement of "clinical pharmacy". 1969.

PMID- 17200422
TI  - Core requirements of the adenine riboswitch aptamer for ligand binding.
AB  - The adenine riboswitch aptamer, the A box, positively regulates gene expression
      upon adenine binding. To provide insight into structure-function relationships,
      important for the adenine riboswitch aptamer, we have created alignments for six
      aptamer sequences that reveal the core requirements. In addition, 2-aminopurine
      (2AP) binding studies have been used to test the consensus sequence derived from
      the alignment. Overall, the consensus secondary structure is consistent with 2AP
      binding studies. However, a position in the core, previously identified as
      variable, shows restriction in nucleotide sequence. Furthermore, this restriction
      is found to be related with the ligand specificity of the riboswitch. The
      implications of this relationship for the riboswitch gene regulation mechanism
      are discussed.

PMID- 17200424
TI  - Pharmacy's directions. 1969.

PMID- 17200425
TI  - Analysis of empiric antimicrobial strategies for cellulitis in the era of
      methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND: The rise in community-onset methicillin-resistant Staphylococcus
      aureus (MRSA) infections potentially complicates the empiric management of
      cellulitis. The threshold at which drugs active against MRSA, such as clindamycin
      and trimethoprim/sulfamethoxazole (TMP/SMX), should be incorporated into empiric
      therapy is unknown. OBJECTIVE: To evaluate the cost-effectiveness of using
      cephalexin, TMP/SMX, or clindamycin for outpatient empiric therapy of cellulitis,
      given various likelihoods of infection due to MRSA. METHODS: A decision analysis
      of the empiric treatment of cellulitis was performed from the perspective of a
      third-party payer. The model included initial therapy with cephalexin,
      clindamycin, or TMP/SMX, followed by treatment with linezolid in cases of
      clinical failure. Probability and cost estimates were obtained from clinical
      trials, epidemiologic data, and publicly available cost data and were subjected
      to sensitivity analysis. RESULTS: Under the base-case scenario (37% probability
      of infection by S. aureus and a 27% MRSA prevalence), cephalexin was the most
      cost-effective option. Clindamycin became a more cost-effective therapy at MRSA
      probabilities from 41-80% when the probability of staphylococcal infection was
      greater than 40%. TMP/SMX was cost-effective only at very high likelihoods of
      MRSA infection. Variables with the most influence in the model were probability
      of S. aureus being methicillin-resistant, cost of linezolid, probability of a
      cure with cephalexin for a non-MRSA infection, and probability of infection due
      to S. aureus. CONCLUSIONS: Cephalexin remains a cost-effective therapy for
      outpatient management of cellulitis at current estimated MRSA levels. Cephalexin
      was the most cost-effective choice over most of the modeled range of
      probabilities, with clindamycin becoming more cost-effective at high likelihoods
      of MRSA infection. TMP/SMX is unlikely to be cost-effective for treatment of
      simple cellulitis. Further studies of the microbiology of cellulitis, the
      epidemiology of MRSA, and the clinical effectiveness of clindamycin and TMP/SMX
      in skin and soft tissue infections are needed.

PMID- 17200426
TI  - Meta-analysis of risk of malignancy with immunosuppressive drugs in inflammatory
      bowel disease.
AB  - BACKGROUND: There is a concern as to whether long-term administration of
      immunosuppressants in patients with inflammatory bowel disease (IBD) would
      increase the risk of malignancy. OBJECTIVE: To compare the risks of developing
      malignancy between patients with IBD treated with immunosuppressive agents and
      patients with IBD not receiving these agents. METHODS: A systematic literature
      review was conducted, and a meta-analysis was performed on data retrieved from
      cohort studies that followed patients with IBD who received immunosuppressive
      agents for more than a year and documented the incidence of newly developed
      malignancy. An electronic search was conducted using MEDLINE (1966-September
      2006), the Cochrane Library (issue 3, 2006), and Japana Centra Revuo Medicina
      (1981-September 2006). Medical subject headings used in the searches were
      azathioprine, 6-mercaptopurine, cyclosporine, methotrexate, tacrolimus,
      inflammatory bowel disease, and neoplasms. We imposed no language limitation in
      the searches. Additionally, a manual search of reference listings from all
      articles retrieved from the electronic databases was performed. Using data
      obtained from control groups or population-based studies, the incidence of newly
      developed malignancy in patients with IBD treated with immunosuppressive agents
      was compared with that of patients with IBD who were not receiving
      immunosuppressive agents. Statistical analysis for the change in risk of
      developing malignancy was performed using the weighted mean difference (WMD)
      normalized to per person-year and its 95% confidence interval. RESULTS: Nine
      cohort studies met the inclusion criteria for this meta-analysis. Analysis of
      these studies showed no discernible difference (WMD -0.3 x 10(-3)/person-year;
      95% CI -1.2 x 10(-3) to 0.7 x 10(-3)) in the incidence of any kind of malignancy
      in patients with IBD who received immunosuppressants compared with those who did
      not receive immunosuppressants. No significant difference in WMD was observed
      when the data from patients with either Crohn's disease (CD) or ulcerative
      colitis (UC) were analyzed separately. CONCLUSIONS: Our findings suggest that the
      administration of immunosuppressive agents in patients with either CD or UC
      probably does not confer a significantly increased risk of malignancy compared
      with patients with IBD who are not receiving these agents.

PMID- 17200427
TI  - Optimal low-density lipoprotein cholesterol lowering--morning versus evening
      statin administration.
AB  - OBJECTIVE: To determine the best time to administer statins for optimal lowering
      of low-density lipoprotein cholesterol (LDL-C) by reviewing the clinical evidence
      evaluating the chronobiologic effects of morning versus evening statin
      administration. DATA SOURCES: Using the MeSH terms HMG-CoA reductase inhibitors,
      statins, morning and evening dosing, and clinical trials, a literature review was
      conducted to identify articles in MEDLINE (1966-December 2006), International
      Pharmaceutical Abstracts (1970-December 2006), and IOWA Drug Information Systems
      (1985-December 2006). DATA SYNTHESIS: Seven English-language studies evaluating
      morning and evening statin administration were identified and evaluated. Based on
      the available data, simvastatin demonstrated a pronounced LDL-C percentage
      reduction with evening dosing. Although not statistically significant, a trend in
      the LDL-C percentage reduction favoring evening statin administration was noted
      with lovastatin, pravastatin, and rosuvastatin. Atorvastatin demonstrated similar
      LDL-C reduction regardless of administration time. With the exception of
      simvastatin, the trials comparing morning versus evening effects of statins on
      LDL-C have several significant methodologic shortcomings, including small sample
      size, lack of statistical power, and inappropriate exclusion criteria that did
      not include or did not mention drug-induced effects on lipids. CONCLUSIONS: There
      are sufficient data to support evening administration of simvastatin to achieve
      optimal lowering of LDL-C levels. Rigorous and robust trials are necessary to
      determine the best administration time to achieve optimal LDL-C lowering for
      lovastatin, pravastatin, rosuvastatin, atorvastatin, and fluvastatin.

PMID- 17200428
TI  - Probable statin-induced testicular pain.
AB  - OBJECTIVE: To describe a case of a patient experiencing testicular pain on 3
      occasions after taking 3 different statins. CASE SUMMARY: A 54-year-old man with
      hyperlipidemia was started on lovastatin therapy. His other medications included
      aspirin, levothyroxine, buspirone, and atenolol. Seven months after starting
      lovastatin, the patient experienced testicular discomfort that resolved upon
      discontinuation of the drug. Afterward, he started simvastatin and again
      experienced testicular discomfort. The simvastatin was changed to atorvastatin,
      and the pain resolved. However, 3 months after starting atorvastatin, the patient
      developed testicular pain, which resolved after the drug was stopped. During each
      of the episodes, the patient's pain increased when he was sitting, driving, or
      wearing tight clothing. The Naranjo probability scale indicates that statins
      probably caused the patient's pain. DISCUSSION: Testicular pain is rarely caused
      by medications. Product labeling for statins does not list urinary adverse events
      as common. However, labeling for atorvastatin and pravastatin lists rare urologic
      adverse effects. A literature search did not reveal any previously reported cases
      of testicular adverse effects from statins. However, statins have been shown to
      inhibit cholesterol synthesis in the testis. Some data indicate that statins
      reduce serum testosterone concentrations, but other data indicate that statins
      have no effect on sex hormones or spermatogenesis. Data are also available
      indicating that aspirin might affect testosterone concentrations and testicular
      function. It is difficult to know whether either of the above hormonal mechanisms
      was associated with our patient's testicular discomfort, but the time course and
      challenge/rechallenge aspects of the case suggest that the statins were the
      cause. CONCLUSIONS: Urologic adverse effects of statins rarely occur but should
      not be overlooked by medical providers.

PMID- 17200429
TI  - Rapid desensitization protocols for patients with cardiovascular disease and
      aspirin hypersensitivity in an era of dual antiplatelet therapy.
AB  - OBJECTIVE: To review the available protocols for rapid desensitization of
      patients with aspirin hypersensitivity and apply the data for use in patients
      with cardiovascular disease who would benefit from the dual antiplatelet therapy.
      DATA SOURCES: A literature search was conducted via MEDLINE from 1966 to December
      2006. Main search terms included: aspirin sensitivity, aspirin allergy, aspirin
      desensitization, aspirin-induced asthma, aspirin therapy, and aspirin intolerance
      syndrome. STUDY SELECTION AND DATA EXTRACTION: Articles describing rapid aspirin
      desensitization protocols were selected for review. Literature pertaining to
      aspirin hypersensitivity, drug desensitization, and the use of aspirin and dual
      antiplatelet therapy was also examined. Three rapid desensitization protocols
      were identified and evaluated. DATA SYNTHESIS: While landmark studies
      demonstrated that dual antiplatelet therapy with aspirin and clopidogrel
      significantly reduces mortality and morbidity in acute coronary syndromes and
      coronary stenting, patients with aspirin hypersensitivity are frequently managed
      with clopidogrel alone with no supporting data. Approximately 10% of the
      population experiences hypersensitivity to aspirin, which can manifest as asthma
      exacerbations, rhinorrhea, angioedema, urticaria, and anaphylaxis. The
      hypersensitivity reaction is mediated through aspirin-directed antibodies or by
      excessive leukotriene production. The desensitization process involved depletion
      of these mediators, as well as down-regulation of leukotriene receptors. Two
      groups of investigators developed rapid protocols to desensitize patients with
      aspirin hypersensitivity safely and effectively. The rapid protocol developed by
      Wong provides benefits over other protocols with its low starting dose and
      completion in less than 3 hours, low incidence of adverse effects, and high
      success rate in aspirin desensitization. CONCLUSIONS: The Wong protocol is an
      attractive option for the rapid desensitization of patients requiring dual
      antiplatelet therapy with aspirin and clopidogrel in the perimyocardial
      infarction period.

PMID- 17200430
TI  - Prevention of postoperative nausea and vomiting.
AB  - OBJECTIVE: To review the literature on the prevention of postoperative nausea and
      vomiting (PONV) in adults. DATA SOURCES: Literature retrieval was accessed
      through MEDLINE (1966-December 2006) using the terms postoperative nausea and
      vomiting, prevention and treatment. Article references were hand-searched for
      additional relevant articles and abstracts. STUDY SELECTION AND DATA EXTRACTION:
      All studies published in English were evaluated. Those dealing with prevention
      and treatment of PONV in adults were included in the review. DATA SYNTHESIS:
      Evidence suggests that providing prophylactic antiemetic medications in high-risk
      surgical patients is warranted. 5-HT3 receptor antagonists are widely used, with
      no one agent being clearly superior. However, studies have shown other types of
      agents to be more cost-effective. CONCLUSIONS: The first step in the prevention
      of PONV is assessment and reduction of risk factors. Although nonpharmacologic
      therapies may play a role in the treatment of PONV, the mainstay of therapy for
      PONV is pharmacologic modalities. Patients at moderate to high risk for PONV need
      prophylactic antiemetic therapy. High-risk patients may require combination
      therapy with 2 or 3 agents from different antiemetic classes. Rescue antiemetic
      therapy is needed by patients who actually develop PONV. The agents of choice in
      such cases should be from antiemetic classes different from those used for
      prophylaxis of PONV.

PMID- 17200431
TI  - Clopidogrel-precipitated rhabdomyolysis in a stable heart transplant patient.
AB  - OBJECTIVE: To report the case of an orthotopic heart transplant recipient who
      developed rhabdomyolysis precipitated by the addition of clopidogrel to the
      existing regimen of cyclosporine and atorvastatin, which had been tolerated for
      more than 3 years without adverse effects or laboratory evidence of myositis.
      CASE SUMMARY: Fourteen years after cardiac transplantation, a 58-year-old woman
      began a planned 4 week course of clopidogrel 75 mg/day following coronary
      angioplasty and placement of a stent in the left circumflex coronary artery.
      Almost 4 weeks later, she presented with severe muscle pain and weakness and
      laboratory evidence of rhabdomyolysis, with marked elevations of plasma creatine
      kinase (96,000 U/L) and urine myoglobin (332,872 microg/L) as well as early acute
      renal failure (serum creatinine 2.9 mg/dL). Symptoms and laboratory abnormalities
      resolved with cessation of cyclosporine, atorvastatin, and clopidogrel.
      Clopidogrel was not restarted, while atorvastatin and cyclosporine were; the
      patient had no recurrence of symptoms up to 15 months later. DISCUSSION: Both
      atorvastatin and cyclosporine, as well as clopidogrel's active thiol derivative,
      are metabolized by the cytochrome P450 3A4 isoenzyme. Cyclosporine is also a
      moderate inhibitor of this isoenzyme. We postulate that competition between
      atorvastatin and clopidogrel for CYP3A4 receptors, already partially inhibited by
      cyclosporine, led to increased atorvastatin concentrations, resulting in the
      acute onset of rhabdomyolysis. This theory is further supported by the patient's
      continued ability to tolerate the combination of atorvastatin and cyclosporine,
      without clopidogrel, on rechallenge. Use of the Naranjo probability scale
      revealed that rhabdomyolysis was probably precipitated by the addition of
      clopidogrel to the stable baseline regimen of cyclosporine and atorvastatin.
      CONCLUSIONS: Practitioners must be conscious of the potential for adverse effects
      when prescribing clopidogrel to heart transplant patients who are concomitantly
      receiving cyclosporine and a statin. If concomitant administration is required,
      careful clinical and laboratory monitoring of the patient is necessary.

PMID- 17200432
TI  - Cerebral blood flow autoregulation and edema formation during pregnancy in
      anesthetized rats.
AB  - Eclampsia is considered a form of hypertensive encephalopathy in which an acute
      elevation in blood pressure causes autoregulatory breakthrough, blood-brain
      barrier disruption, and edema formation. We hypothesized that pregnancy
      predisposes the brain to eclampsia by lowering the pressure of autoregulatory
      breakthrough and enhancing cerebral edema formation. Because NO production is
      increased in pregnancy, we also investigated the role of NO in modulating
      autoregulation. Cerebral blood flow autoregulation was determined by
      phenylephrine infusion and laser Doppler flowmetry. Four groups were studied:
      untreated nonpregnant (n=7) and late-pregnant (days 19 to 21; n=8) Sprague-Dawley
      rats and nonpregnant (n=8) and late-pregnant (n=8) animals treated with an NO
      synthase inhibitor (N(G)-nitro-l-arginine methyl ester; 0.5 to 0.7 g/L). Brain
      water content and blood-brain barrier permeability to sodium fluorescein were
      determined after breakthrough. Pregnancy caused no change in autoregulation or
      the pressure of breakthrough. However, treatment with the NO synthase inhibitor
      significantly increased the pressure of autoregulatory breakthrough (nonpregnant:
      183.6+/-3.0 mm Hg versus 212.0+/-2.8 mm Hg, P<0.05; late-pregnant: 180.8+/-3.2 mm
      Hg versus 209.3+/-4.7 mm Hg, P<0.05). After autoregulatory breakthrough, only
      late-pregnant animals showed a significant increase in cerebral edema formation,
      which was attenuated by NO synthase inhibition. There was no difference in blood
      brain barrier permeability between nonpregnant and late-pregnant animals in
      response to acute hypertension, suggesting that pregnancy may predispose the
      brain to eclampsia by increasing cerebral edema through increased hydraulic
      conductivity.

PMID- 17200433
TI  - Age-specific relationship of aortic pulse wave velocity with left ventricular
      geometry and function in hypertension.
AB  - Aortic pulse wave velocity (PWV), generally considered an intrinsic marker of
      arterial stiffness, might depend in part on the velocity of myocardial fiber
      shortening, but the relation between PWV and myocardial function in humans has
      been understudied. A total of 237 untreated hypertensive subjects over a wide age
      range (18 to 88 years) underwent aortic PWV determination and echocardiography,
      from which the mean velocity of circumferential fiber shortening was calculated
      as a measure of the velocity of myocardial shortening, and relative wall
      thickness was taken as a measure of left ventricular concentric remodeling.
      Patients were divided in 3 age groups (<40 years, 40 to 59 years, and >or=60
      years). In the young, aortic PWV was directly associated with heart rate
      corrected velocity of circumferential fiber shortening (r=0.39; P=0.002) but not
      to relative wall thickness (r=-0.01; P=0.95). The opposite was found in the older
      group, in which aortic PWV was accompanied by a concentric left ventricular
      geometric pattern (r=0.44 with relative wall thickness; P=0.009) and a reduced
      velocity of circumferential fiber shortening (r=-0.54; P<0.001) and stress
      corrected midwall fractional shortening (r=-0.56; P<0.001). Intermediate values
      were found in the middle-aged group (r=0.23; P<0.01 with relative wall thickness;
      r=-0.07, P value not significant with velocity of circumferential fiber
      shortening). In conclusion, the relation between aortic PVW and the left
      ventricle is strongly age dependent. These data suggest that, in young people,
      aortic PWV is partly determined by an increased velocity of myocardial
      shortening. With increasing age, a relationship between aortic PWV (as a measure
      of arterial stiffness) and left ventricular concentric geometry emerges, which
      ultimately leads to a depressed ventricular systolic function.

PMID- 17200434
TI  - Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1.
AB  - Accumulating evidence suggests that mineralocorticoid receptor blockade
      effectively reduces proteinuria in hypertensive patients. However, the mechanism
      of the antiproteinuric effect remains elusive. In this study, we investigated the
      effects of aldosterone on podocyte, a key player of the glomerular filtration
      barrier. Uninephrectomized rats were continuously infused with aldosterone and
      fed a high-salt diet. Aldosterone induced proteinuria progressively, associated
      with blood pressure elevation. Notably, gene expressions of podocyte-associated
      molecules nephrin and podocin were markedly decreased in aldosterone-infused rats
      at 2 weeks, with a gradual decrease thereafter. Immunohistochemical studies and
      electron microscopy confirmed the podocyte damage. Podocyte injury was
      accompanied by renal reduced nicotinamide-adenine dinucleotide phosphate oxidase
      activation, increased oxidative stress, and enhanced expression of aldosterone
      effector kinase Sgk1. Treatment with eplerenone, a selective aldosterone receptor
      blocker, almost completely prevented podocyte damage and proteinuria, with
      normalization of elevated reduced nicotinamide-adenine dinucleotide phosphate
      oxidase activity. In addition, proteinuria, podocyte damage, and Sgk1
      upregulation were significantly alleviated by tempol, a membrane-permeable
      superoxide dismutase, suggesting the pathogenic role of oxidative stress.
      Although hydralazine treatment almost normalized blood pressure, it failed to
      improve proteinuria and podocyte damage. In cultured podocytes with consistent
      expression of mineralocorticoid receptor, aldosterone stimulated membrane
      translocation of reduced nicotinamide-adenine dinucleotide phosphate oxidase
      cytosolic components and oxidative stress generation in podocytes. Furthermore,
      aldosterone enhanced the expression of Sgk1, which was inhibited by
      mineralocorticoid receptor antagonist and tempol. In conclusion, podocytes are
      injured at the early stage in aldosterone-infused rats, resulting in the
      occurrence of proteinuria. Aldosterone can directly modulate podocyte function,
      possibly through the induction of oxidative stress and Sgk1.

PMID- 17200436
TI  - Mechanisms of oxidative stress-induced increase in salt sensitivity and
      development of hypertension in Sprague-Dawley rats.
AB  - High salt intake produces vascular changes that contribute to the development of
      hypertension in salt-sensitive individuals. Because reactive oxygen species play
      a role in the pathogenesis of cardiovascular diseases, we investigated whether
      oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats
      were divided in different groups and received tap water (vehicle), 30 mmol/L of l
      buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus
      HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days.
      Compared with vehicle, BSO treatment caused oxidative stress and mild increase in
      blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased
      response to endothelium-independent vasorelaxants. In HS-treated rats, the
      response to vasoactive agents, as well as blood pressure, was unaffected.
      Concomitant treatment of rats with BSO and HS produced a marked increase in blood
      pressure and a decreased response to both endothelium-dependent and endothelium
      independent vasorelaxants with an increase in EC(50). Incubation of aortic tissue
      from BSO-treated rats with sodium nitroprusside showed decreased cGMP
      accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol
      decreased oxidative stress, normalized blood pressure, and restored NO signaling
      and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude
      that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces
      NO levels by decreasing the NO synthase activity. These phenomena collectively
      result in reduced responsiveness to both endothelium -dependent and endothelium-
      independent vasorelaxants and may contribute to salt-sensitive hypertension.

PMID- 17200435
TI  - Elevated blood pressure in transgenic lipoatrophic mice and altered vascular
      function.
AB  - The role of perivascular fat in the control of vascular function was studied
      using lipoatrophic A-ZIP/F1 transgenic mice. Only a small amount of brown fat was
      found around the aorta but not around mesenteric arteries. Blood pressure of A
      ZIP/F1 mice became higher than wild-type (WT) mice from 10 weeks of age. The
      presence of perivascular fat reduced the contraction of WT aorta to phenylephrine
      and serotonin, whereas this effect was either absent or less prominent in A
      ZIP/F1 aorta. In WT mice, transfer of solution incubated with aorta with fat to
      aorta with fat removed caused a relaxation response, but not in A-ZIP/F1 mice,
      indicating the release of a relaxation factor from perivascular fat in WT aorta.
      This factor was acting through the activation of calcium-dependent potassium
      channels. Perfusion of phenylephrine to the isolated mesenteric bed caused a
      higher increase in perfusion pressure in A-ZIP/F1 than in WT mice. Contractile
      response of aorta to angiotensin II (Ang II) was mediated by Ang II type 1
      receptors and was higher in A-ZIP/F1 than in WT mice. Expression of Ang II type 1
      receptors but not Ang II type 2 receptors was higher in aorta of A-ZIP/F1 than WT
      mice. Treatment with an Ang II type 1 receptor antagonist (TCV 116, 10 mg/kg per
      day) for 2 weeks normalized the blood pressure of A-ZIP/F1 mice. These results
      suggest that the absence of perivascular fat tissue, which enhances the
      contractile response of the blood vessels to agonists, and an upregulation of
      vascular Ang II type 1 receptors in A-ZIP/F1 mice, are some of the mechanisms
      underlying the blood pressure elevation in these lipoatrophic mice.

PMID- 17200437
TI  - Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors.
AB  - The endothelium regulates vascular tone through the release of a number of
      soluble mediators, including NO, prostaglandin I2, and endothelium-derived
      hyperpolarizing factor. Epoxyeicosatrienoic acids are cytochrome P450 epoxygenase
      metabolites of arachidonic acid. They are synthesized by the vascular endothelium
      and open calcium-activated potassium channels, hyperpolarize the membrane, and
      relax vascular smooth muscle. Endothelium-dependent relaxations to acetylcholine,
      bradykinin, and shear stress that are not inhibited by cyclooxygenase and NO
      synthase inhibitors are mediated by the endothelium-derived hyperpolarizing
      factor. In arteries from experimental animals and humans, the non-NO, non
      prostaglandin-mediated relaxations and endothelium-dependent hyperpolarizations
      are blocked by cytochrome P450 inhibitors, calcium-activated potassium channel
      blockers, and epoxyeicosatrienoic acid antagonists. Acetylcholine and bradykinin
      stimulate epoxyeicosatrienoic acid release from endothelial cells and arteries.
      These findings indicate that epoxyeicosatrienoic acids act as endothelium-derived
      hyperpolarizing factors and regulate arterial tone.

PMID- 17200439
TI  - The -20 and -217 promoter variants dominate differential angiotensinogen
      haplotype regulation in angiotensinogen-expressing cells.
AB  - A number of naturally occurring polymorphisms exist in the human angiotensinogen
      locus, some of which have been associated with essential hypertension,
      preeclampsia, and other medical disorders. However, to date there has been no
      comprehensive determination of the significance of specific haplotypes in
      relation to the regulation of angiotensinogen expression. We cloned the promoters
      extending from -1219 to +125 bp from 11 ethnically diverse individuals to acquire
      a representative cross-section of known haplotype diversity. Eight nonredundant
      haplotypes were identified, fused to luciferase, and studied for their effect on
      transcriptional regulation in human astrocyte, proximal tubule, and hepatocyte
      cell lines endogenously expressing angiotensinogen and in a mouse adipocyte cell
      line. The studies were carried out under baseline conditions, in the presence of
      the angiotensinogen enhancer, and in response to hormonal stimulation by
      dexamethasone, beta-estradiol, or testosterone. A statistical model was then
      constructed to assess the significance of individual polymorphisms. The
      polymorphisms with the greatest effect on transcription in these cell lines were
      located at -20 and -217. There were modest haplotype-specific effects of the
      angiotensinogen enhancer and no haplotype-specific effects of beta-estradiol,
      dexamethasone, or testosterone treatment. We conclude the following: (1) the -20
      and -217 polymorphisms have the largest influence on angiotensinogen
      transcription, (2) other polymorphisms have a much smaller impact on
      angiotensinogen transcription, and (3) the transcriptional influence of the
      promoter polymorphisms may act cell specifically. Therefore, our data support a
      hypothesis that polymorphisms in the angiotensinogen promoter may act cell
      specifically to differentially regulate the level of angiotensinogen
      transcription in angiotensin-producing tissues.

PMID- 17200440
TI  - Cardiac tissue engineering in an in vivo vascularized chamber.
AB  - BACKGROUND: Cardiac tissue engineering offers the prospect of a novel treatment
      for acquired or congenital heart defects. We have created vascularized pieces of
      beating cardiac muscle in the rat that are as thick as the adult rat right
      ventricle wall. METHOD AND RESULTS: Neonatal rat cardiomyocytes in Matrigel were
      implanted with an arteriovenous blood vessel loop into a 0.5-mL patented tissue
      engineering chamber, located subcutaneously in the groin. Chambers were harvested
      1, 4, and 10 weeks after insertion. At 4 and 10 weeks, all constructs that grew
      in the chambers contracted spontaneously. Immunostaining for alpha-sarcomeric
      actin, troponin, and desmin showed that differentiated cardiomyocytes present in
      tissue at all time points formed a network of interconnected cells within a
      collagenous extracellular matrix. Constructs at 4 and 10 weeks were extensively
      vascularized. The maximum thickness of cardiac tissue generated was 1983 microm.
      Cardiomyocytes increased in size from 1 to 10 weeks and were positive for the
      proliferation markers Ki67 and PCNA. Connexin-43 stain indicated that gap
      junctions were present between cardiomyocytes at 4 and 10 weeks. Echocardiograms
      performed between 4 and 10 weeks showed that the tissue construct contracted
      spontaneously in vivo. In vitro organ bath experiments showed a typical cardiac
      muscle length-tension relationship, the ability to be paced from electrical field
      pulses up to 3 Hz, positive chronotropy to norepinephrine, and positive inotropy
      in response to calcium. CONCLUSIONS: In summary, the use of a vascularized tissue
      engineering chamber allowed generation of a spontaneously beating 3-dimensional
      mass of cardiac tissue from neonatal rat cardiomyocytes. Further development of
      this vascularized model will increase the potential of cardiac tissue engineering
      to provide suitable replacement tissues for acquired and congenital defects.

PMID- 17200441
TI  - Hyperhomocysteinemia alters cardiac substrate metabolism by impairing nitric
      oxide bioavailability through oxidative stress.
AB  - BACKGROUND: Hyperhomocysteinemia (HHcy) has been considered a vascular disease
      associated with increased levels of oxidative stress that results in scavenging
      of NO. However, little is known of the impact of HHcy on cardiac function and
      especially myocardial metabolism. METHODS AND RESULTS: L-Homocysteine was
      intravenously infused into conscious dogs, and the dogs were fed methionine to
      increase plasma homocysteine to 10 micromol/L for acute and 24 micromol/L for
      chronic HHcy. There was no significant change in hemodynamics with HHcy.
      Veratrine-induced, NO-dependent, coronary vasodilation (Bezold-Jarisch reflex)
      was reduced by 32% but was restored by simultaneous intravenous infusion of
      ascorbic acid or apocynin. Acute and chronic HHcy significantly increased uptake
      of glucose and lactate and decreased uptake of free fatty acid by the heart. HHcy
      significantly decreased bradykinin- or carbachol-induced reduction of myocardial
      oxygen consumption in vitro, and this effect was completely restored by
      coincubation with ascorbic acid, Tempol, or apocynin. Western blot analysis
      indicated an increase in Nox2 (82%) and a reduction in endothelial nitric oxide
      synthase (39%), phospho-endothelial nitric oxide synthase (39%), and superoxide
      dismutase-1 (45%). Microarray analysis of gene expression in heart tissue from
      chronic HHcy indicated a switch in cardiac phenotype to enzymes that metabolize
      glucose. CONCLUSIONS: HHcy directly modulates substrate use by the heart
      independent of changes in hemodynamics or ventricular function by reducing NO
      bioavailability through the generation of superoxide. The progression of cardiac
      or coronary heart disease associated with HHcy should be evaluated in light of
      the impact of alterations in the regulation of cardiac metabolism and substrate
      use.

PMID- 17200442
TI  - Tumor necrosis factor-alpha induces endothelial dysfunction in Lepr(db) mice.
AB  - BACKGROUND: We hypothesized that the inflammatory cytokine tumor necrosis factor
      alpha (TNF) produces endothelial dysfunction in type 2 diabetes. METHODS AND
      RESULTS: In m Lepr(db) control mice, sodium nitroprusside and acetylcholine
      induced dose-dependent vasodilation, and dilation to acetylcholine was blocked by
      the NO synthase inhibitor N(G)-monomethyl-L-arginine. In type 2 diabetic
      (Lepr(db)) mice, acetylcholine- or flow-induced dilation was blunted compared
      with m Lepr(db), but sodium nitroprusside produced comparable dilation. In
      Lepr(db) mice null for TNF (db(TNF-)/db(TNF-)), dilation to acetylcholine or flow
      was greater than in diabetic Lepr(db) mice and comparable to that in controls.
      Plasma concentration of TNF was significantly increased in Lepr(db) versus m
      Lepr(db) mice. Real-time polymerase chain reaction and Western blotting showed
      that mRNA and protein expression of TNF and nuclear factor-kappaB were higher in
      Lepr(db) mice than in controls. Administration of anti-TNF or soluble receptor of
      advanced glycation end products attenuated nuclear factor-kappaB and TNF
      expression in the Lepr(db) mice. Immunostaining results show that TNF in mouse
      heart is localized predominantly in vascular smooth muscle cells rather than in
      endothelial cells and macrophages. Superoxide generation was elevated in vessels
      from Lepr(db) mice versus controls. Administration of the superoxide scavenger
      TEMPOL, NAD(P)H oxidase inhibitor (apocynin), or anti-TNF restored endothelium
      dependent dilation in Lepr(db) mice. NAD(P)H oxidase activity, protein expression
      of nitrotyrosine, and hydrogen peroxide production were increased in Lepr(db)
      mice (compared with controls), but these variables were restored to control
      levels by anti-TNF. CONCLUSIONS: Advanced glycation end products/receptor of
      advanced glycation end products and nuclear factor-kappaB signaling play pivotal
      roles in TNF expression through an increase in circulating and/or local vascular
      TNF production in the Lepr(db) mouse with type 2 diabetes. Increases in TNF
      expression induce activation of NAD(P)H oxidase and production of reactive
      oxidative species, leading to endothelial dysfunction in type 2 diabetes.

PMID- 17200444
TI  - Elevated homocysteine is associated with reduced regional left ventricular
      function: the Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: An elevated homocysteine (Hcy) level has been reported to be a risk
      factor for the development of congestive heart failure in individuals free of
      myocardial infarction. In this study, we aim to investigate the relationship
      between Hcy levels and regional left ventricular function in an asymptomatic
      population. METHOD AND RESULTS: Regional peak systolic midwall circumferential
      strains were calculated from 1178 tagged magnetic resonance imaging studies in
      participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Left
      ventricular regions were defined by coronary territories (left anterior
      descending, left circumflex, right coronary artery). For the 1178 study
      participants (66+/-10 years of age, 58% males), the median (interquartile range)
      of Hcy was 9.1 (9.0 to 9.3). After adjustment for traditional risk factors, race,
      height, weight, left ventricular end-diastolic mass/volume, serum creatinine, and
      measures of atherosclerosis, reduced regional myocardial circumferential
      shortening across sex-specific quartiles of plasma Hcy in the left anterior
      descending (P=0.038) and left circumflex (P=0.009) regions persisted, which
      indicated an important association of reduced function with elevated Hcy.
      Multiple linear regression analyses confirmed that circumferential systolic
      dysfunction was associated with log transformed Hcy levels in the left anterior
      descending (P=0.004) and left circumflex (P=0.0002) regions. In the fully
      adjusted model, the odds ratio for left ventricular strains below the 10th
      percentile with 1 SD increases in log-transformed Hcy was 1.33 (95% confidence
      interval, 1.04 to 1.70; P=0.022) for the left anterior descending, 1.28 (95%
      confidence interval, 1.00 to 1.64; P=0.046) for the left circumflex, and 1.32
      (95% confidence interval, 1.03 to 1.69; P=0.025) for the right coronary artery
      region. CONCLUSIONS: In this asymptomatic population, an elevated Hcy level is
      associated with reduced regional left ventricular systolic function detected by
      tagged magnetic resonance imaging.

PMID- 17200443
TI  - Rapid detection of myocardial infarction by subsecond, free-breathing delayed
      contrast-enhancement cardiovascular magnetic resonance.
AB  - BACKGROUND: An ultrafast, delayed contrast-enhancement cardiovascular magnetic
      resonance technique that can acquire subsecond, "snapshot" images during free
      breathing (subsecond) is becoming widely available. This technique provides
      myocardial infarction (MI) imaging with complete left ventricular coverage in <
      30 seconds. However, the accuracy of this technique is unknown. METHODS AND
      RESULTS: We prospectively compared subsecond imaging with routine breath-hold
      delayed contrast-enhancement cardiovascular magnetic resonance (standard) in
      consecutive patients. Two cohorts with unambiguous standards of truth were
      prespecified: (1) patients with documented prior MI (n=135) and (2) patients
      without MI and with low likelihood of coronary disease (lowest Framingham risk
      category; n=103). Scans were scored masked to identity and clinical information.
      Sensitivity, specificity, and accuracy of subsecond imaging for MI diagnosis were
      87%, 96%, and 91%, respectively. Compared with the standard technique (98%, 100%,
      99%), the subsecond technique had modestly reduced sensitivity (P=0.0001), but
      specificity was excellent. Missed infarcts were generally small or subendocardial
      (87%). Overall, regional transmural extent of infarction scores were highly
      concordant (2083/2294; 91%); however, 51 of 337 regions (15%) considered
      predominantly infarcted (> 50% transmural extent of infarction) by the standard
      technique were considered viable (< or = 25% transmural extent of infarction) by
      the subsecond technique. Quantitative analysis demonstrated moderately reduced
      contrast-to-noise ratios for subsecond imaging between infarct and remote
      myocardium (12.0+/-7.2 versus 20.1+/-6.6; P<0.0001) and infarct and left
      ventricular cavity (-2.5+/-2.7 versus 3.6+/-3.7; P<0.0001). CONCLUSIONS: MI can
      be rapidly detected by subsecond delayed contrast-enhancement cardiovascular
      magnetic resonance during free breathing with high accuracy. This technique could
      be considered the preferred approach in patients who are more acutely ill or
      unable to hold their breath. However, compared with standard imaging, sensitivity
      is mildly reduced, and the transmural extent of infarction may be underestimated.

PMID- 17200445
TI  - Early outcomes of tricuspid valve replacement in young children.
AB  - BACKGROUND: Early outcomes after tricuspid valve replacement in young children
      are ill defined. The experience of the Pediatric Cardiac Care Consortium (45
      centers, 1984 to 2002) was reviewed to evaluate the results of tricuspid valve
      replacement in children <6 years of age. METHODS AND RESULTS: Ninety-seven
      patients who underwent initial tricuspid valve replacement are included in the
      present analysis. The most frequent cardiac diagnoses were Ebstein's anomaly
      (40%), pulmonary atresia (11%), and tetralogy of Fallot (8%). Age at tricuspid
      valve replacement was 2.9+/-1.7 years (mean+/-SD). Mean patient weight was 12.7+/
      6.1 kg. The major outcome was survival to discharge. Associations among age,
      diagnosis, valve type/size, and outcome were evaluated through the use of chi2
      analysis and logistic regression model fitting approaches. Hospital mortality was
      26% and was very high (64%) in patients <1 year of age. A large size-to-weight
      ratio was the strongest predictor of mortality based on multivariable analysis
      (P<0.001). Mortality was 54% for patients with a size-to-weight ratio >2.5. Other
      complications included heart block requiring a pacemaker (13%) and thrombosis
      (5%). Pacemaker implantation was associated with the use of a mechanical valve
      (23% versus 6% bioprosthetic valve; P=0.01) CONCLUSIONS: Tricuspid valve
      replacement in young children is associated with high mortality, especially in
      infants <1 year of age. Surgical options other than tricuspid valve replacement
      such as transplantation may need to be considered in infants.

PMID- 17200446
TI  - Images in cardiovascular medicine. Serial assessment of liquefaction necrosis of
      mitral annular calcification by echocardiography and multislice computed
      tomography.

PMID- 17200448
TI  - Images in cardiovascular medicine. Left main coronary artery compression
      syndrome: evaluation with 64-slice cardiac multidetector computed tomography.

PMID- 17200447
TI  - Images in cardiovascular medicine. Papillary fibroelastoma of the aortic valve:
      appearance in 64-slice spiral computed tomography, magnetic resonance imaging,
      and echocardiography.

PMID- 17200450
TI  - A view from Latvia.

PMID- 17200449
TI  - Letter by Selvaraj and Chauhan regarding article, "Upsurge in T-wave alternans
      and nonalternating repolarization instability precedes spontaneous initiation of
      ventricular tachyarrhythmias in humans".

PMID- 17200451
TI  - Degenerating heart valves: fill them up with filamin?

PMID- 17200453
TI  - Congenital and acquired pulmonary vein stenosis.

PMID- 17200452
TI  - Connecting the missing link between dilated cardiomyopathy and viral myocarditis:
      virus, cytoskeleton, and innate immunity.

PMID- 17200454
TI  - Survival methods.

PMID- 17200455
TI  - Who's afraid of ligand-macromolecule interactions in complex physiological
      systems?

PMID- 17200456
TI  - Folk neurology and the remaking of identity.

PMID- 17200458
TI  - Nicotinic and opioid receptor interactions in nicotine addiction.

PMID- 17200457
TI  - Disrupting calcium channel expression to lower blood pressure: new targeting of a
      well-known channel.

PMID- 17200459
TI  - Calcium: a role for neuroprotection and sustained adaptation.
AB  - Sustained increases in intracellular calcium following prolonged seizures or
      other neurological insults have been thought to be responsible for neuronal cell
      death for well over two decades. For example, a seizure or a stroke can lead to
      excessive release of glutamate, an endogenous excitotoxin. Overactivation of
      receptors that interact with glutamate will raise calcium levels to stimulate a
      variety of signaling pathways that can impair neuronal respiration and eventually
      kill neurons. On the contrary, recent evidence shows that under numerous
      conditions calcium can prevent neurons from dying. Experimental epilepsy and
      ischemia models show that protection of neurons appears to depend upon the age of
      the animal, the amount and route of calcium elevation, timing of initial insults,
      and brain regions involved. This review will discuss novel findings on the
      protective signaling role of calcium under a wide range of pathological
      conditions.

PMID- 17200461
TI  - Animal models and brain circuits in drug addiction.
AB  - Animal models in the field of addiction are considered to be among the best
      available models of neuropsychiatric disease. These models have undergone a
      number of refinements that allow deeper understanding of the circuitry involved
      in initiating drug seeking and relapse. Notably, the demonstrable involvement of
      classic corticostriatal habit circuitry and the engagement of prefrontal cortical
      circuits in extinction training may have relevance to the therapeutic modulation
      of habit circuitry and drug addiction in humans.

PMID- 17200462
TI  - The cover. Piette's House at Montfoucault.

PMID- 17200463
TI  - A piece of my mind. A place in the sun.

PMID- 17200464
TI  - University of Maryland School of Medicine: 200 years for nation's first public
      medical school.

PMID- 17200460
TI  - The prokineticins: a novel pair of regulatory peptides.
AB  - Secreted peptides play broad regulatory roles in brain function and elsewhere in
      the body. Prokineticins are a pair of newly identified regulatory peptides that
      signal through two highly homologous G protein-coupled receptors. Prokineticins
      possess a unique structural motif of five disulfide bonds and a completely
      conserved N-terminal hexapeptide sequence that is essential to biological
      activity. Diverse biological functions, including roles in development and cell
      differentiation, have been assigned to the prokineticins. A network of genes,
      subject to various transcriptional factors, may functionally converge on the
      prokineticins as regulatory targets.

PMID- 17200465
TI  - Arthritis clinical trial results revealed.

PMID- 17200466
TI  - Healing power found in "nano knitting".

PMID- 17200467
TI  - Changing premedical requirements.

PMID- 17200468
TI  - Changing premedical requirements.

PMID- 17200469
TI  - Changing premedical requirements.

PMID- 17200470
TI  - Evaluating education in evidence-based practice.

PMID- 17200471
TI  - Left ventricular hypertrophy regression and atrial fibrillation incidence.

PMID- 17200472
TI  - Fluid replacement for severe hyponatremia.

PMID- 17200473
TI  - Does this patient have a migraine?

PMID- 17200474
TI  - Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing
      primary percutaneous coronary intervention: a randomized controlled trial.
AB  - CONTEXT: Reperfusion with percutaneous transluminal coronary intervention (PCI)
      is effective at improving outcomes in patients with acute ST-elevation myocardial
      infarction (STEMI). However, in patients without prompt reestablishment of brisk
      coronary flow and tissue perfusion, mortality remains high, providing an
      opportunity for novel treatments, including anti-inflammatory agents. OBJECTIVE:
      To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody
      that binds the C5 component of complement, as an adjunct to PCI in improving 30
      day mortality from STEMI. DESIGN, SETTING, AND PATIENTS: This trial was a
      prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the
      intravenous administration of pexelizumab in conjunction with primary PCI in
      STEMI with prespecified high-risk electrocardiographic findings. The trial was
      intended to enroll 8500 patients, but in conjunction with the US Food and Drug
      Administration enrollment was modified to 5745 patients presenting from 296
      hospitals in 17 countries from July 13, 2004, to May 11, 2006. INTERVENTIONS: Two
      thousand eight hundred eighty-five patients were randomly assigned to receive
      placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus
      prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24
      hours. Patients were randomized within 6 hours of symptom onset. MAIN OUTCOME
      MEASURES: The primary end point was all-cause mortality through day 30. Secondary
      end points were death through day 90 and the composite of death, cardiogenic
      shock, or congestive heart failure through days 30 and 90. RESULTS: No difference
      in mortality through day 30 was observed between the pexelizumab and placebo
      treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in
      the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI],
      0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart
      failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265
      patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P =
      .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%)
      receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). CONCLUSION:
      In this large clinical trial of patients treated with primary PCI for STEMI,
      mortality was low and unaffected by administration of pexelizumab. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00091637.

PMID- 17200475
TI  - Clinical prediction rule for identifying children with cerebrospinal fluid
      pleocytosis at very low risk of bacterial meningitis.
AB  - CONTEXT: Children with cerebrospinal fluid (CSF) pleocytosis are routinely
      admitted to the hospital and treated with parenteral antibiotics, although few
      have bacterial meningitis. We previously developed a clinical prediction rule,
      the Bacterial Meningitis Score, that classifies patients at very low risk of
      bacterial meningitis if they lack all of the following criteria: positive CSF
      Gram stain, CSF absolute neutrophil count (ANC) of at least 1000 cells/microL,
      CSF protein of at least 80 mg/dL, peripheral blood ANC of at least 10,000
      cells/microL, and a history of seizure before or at the time of presentation.
      OBJECTIVE: To validate the Bacterial Meningitis Score in the era of widespread
      pneumococcal conjugate vaccination. DESIGN, SETTING, AND PATIENTS: A multicenter,
      retrospective cohort study conducted in emergency departments of 20 US academic
      medical centers through the Pediatric Emergency Medicine Collaborative Research
      Committee of the American Academy of Pediatrics. All children aged 29 days to 19
      years who presented at participating emergency departments between January 1,
      2001, and June 30, 2004, with CSF pleocytosis (CSF white blood cells > or =10
      cells/microL) and who had not received antibiotic treatment before lumbar
      puncture. MAIN OUTCOME MEASURE: The sensitivity and negative predictive value of
      the Bacterial Meningitis Score. RESULTS: Among 3295 patients with CSF
      pleocytosis, 121 (3.7%; 95% confidence interval [CI], 3.1%-4.4%) had bacterial
      meningitis and 3174 (96.3%; 95% CI, 95.5%-96.9%) had aseptic meningitis. Of the
      1714 patients categorized as very low risk for bacterial meningitis by the
      Bacterial Meningitis Score, only 2 had bacterial meningitis (sensitivity, 98.3%;
      95% CI, 94.2%-99.8%; negative predictive value, 99.9%; 95% CI, 99.6%-100%), and
      both were younger than 2 months old. A total of 2518 patients (80%) with aseptic
      meningitis were hospitalized. CONCLUSIONS: This large multicenter study validates
      the Bacterial Meningitis Score prediction rule in the era of conjugate
      pneumococcal vaccine as an accurate decision support tool. The risk of bacterial
      meningitis is very low (0.1%) in patients with none of the criteria. The
      Bacterial Meningitis Score may be helpful to guide clinical decision making for
      the management of children presenting to emergency departments with CSF
      pleocytosis.

PMID- 17200476
TI  - Association between performance measures and clinical outcomes for patients
      hospitalized with heart failure.
AB  - CONTEXT: Assessment of quality of care in heart failure has focused on the
      development and use of process-based performance measures, with the presumption
      that these processes are associated with improved clinical outcomes. However,
      this link remains largely untested. OBJECTIVE: To examine the relationship
      between current American College of Cardiology/American Heart Association
      (ACC/AHA) performance measures for patients hospitalized with heart failure and
      relevant clinical outcomes. DESIGN, SETTING, AND PATIENTS: The Organized Program
      to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure, a
      registry and performance improvement program for patients hospitalized with heart
      failure. Sixty- to ninety-day postdischarge follow-up data were prospectively
      collected from 5791 patients at 91 US hospitals in a prespecified 10% sample
      between March 2003 and December 2004. Mean patient age was 72.0 years, 51% were
      male, 78% were white, and 42% had ischemic etiology. Multivariable and propensity
      adjusted analyses were performed to assess the process-outcome relationship for
      each performance measure in eligible patients. Additionally, we evaluated the
      process-outcome link of a potential performance measure for beta-blockade at
      discharge among eligible patients hospitalized with heart failure. MAIN OUTCOME
      MEASURES: Sixty- to ninety-day mortality and combined mortality/rehospitalization
      rates. RESULTS: Mortality during follow-up was 8.6% and
      mortality/rehospitalization was 36.2%. None of the 5 ACC/AHA heart failure
      performance measures was significantly associated with reduced early mortality
      risk, and only angiotensin-converting enzyme inhibitor or angiotensin receptor
      blocker use at discharge was associated with 60- to 90-day postdischarge
      mortality or rehospitalization. Beta-blockade at the time of hospital discharge,
      currently not a heart failure performance measure, was strongly associated with
      reduced risk of mortality (hazard ratio, 0.48; 95% confidence interval, 0.30
      0.79; P = .004) and mortality/rehospitalization during follow-up. CONCLUSIONS:
      Current heart failure performance measures, aside from prescription of an
      angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at
      discharge, have little relationship to patient mortality and combined
      mortality/rehospitalization in the first 60 to 90 days after discharge.
      Additional measures and better methods for identifying and validating heart
      failure performance measures may be needed to accurately assess and improve care
      of patients with heart failure.

PMID- 17200477
TI  - Enhancement of claims data to improve risk adjustment of hospital mortality.
AB  - CONTEXT: Comparisons of risk-adjusted hospital performance often are important
      components of public reports, pay-for-performance programs, and quality
      improvement initiatives. Risk-adjustment equations used in these analyses must
      contain sufficient clinical detail to ensure accurate measurements of hospital
      quality. OBJECTIVE: To assess the effect on risk-adjusted hospital mortality
      rates of adding present on admission codes and numerical laboratory data to
      administrative claims data. DESIGN, SETTING, AND PATIENTS: Comparison of risk
      adjustment equations for inpatient mortality from July 2000 through June 2003
      derived by sequentially adding increasingly difficult-to-obtain clinical data to
      an administrative database of 188 Pennsylvania hospitals. Patients were
      hospitalized for acute myocardial infarction, congestive heart failure,
      cerebrovascular accident, gastrointestinal tract hemorrhage, or pneumonia or
      underwent an abdominal aortic aneurysm repair, coronary artery bypass graft
      surgery, or craniotomy. MAIN OUTCOME MEASURES: C statistics as a measure of the
      discriminatory power of alternative risk-adjustment models (administrative,
      present on admission, laboratory, and clinical for each of the 5 conditions and 3
      procedures). RESULTS: The mean (SD) c statistic for the administrative model was
      0.79 (0.02). Adding present on admission codes and numerical laboratory data
      collected at the time of admission resulted in substantially improved risk
      adjustment equations (mean [SD] c statistic of 0.84 [0.01] and 0.86 [0.01],
      respectively). Modest additional improvements were obtained by adding more
      complex and expensive to collect clinical data such as vital signs, blood culture
      results, key clinical findings, and composite scores abstracted from patients'
      medical records (mean [SD] c statistic of 0.88 [0.01]). CONCLUSIONS: This study
      supports the value of adding present on admission codes and numerical laboratory
      values to administrative databases. Secondary abstraction of difficult-to-obtain
      key clinical findings adds little to the predictive power of risk-adjustment
      equations.

PMID- 17200478
TI  - Will my patient fall?
AB  - CONTEXT: Effective multifactorial interventions reduce the frequent falling rate
      of older patients by 30% to 40%. However, clinical consensus suggests reserving
      these interventions for high-risk patients. Limiting fall prevention programs to
      high-risk patients implies that clinicians must recognize features that predict
      future falls. OBJECTIVE: To identify the prognostic value of risk factors for
      future falls among older patients. DATA SOURCES AND STUDY SELECTION: Search of
      MEDLINE (1966-September 2004), CINAHL (1982-September 2004), and authors' own
      files to identify prospective cohort studies of risk factors for falls that
      performed a multivariate analysis of such factors. DATA EXTRACTION: Two reviewers
      independently determined inclusion of articles and assessed study quality.
      Disagreements were resolved by consensus. Included studies were those identifying
      the prognostic value of risk factors for future falls among community-dwelling
      persons 65 years and older. Clinically identifiable risk factors were identified
      across 6 domains: orthostatic hypotension, visual impairment, impairment of gait
      or balance, medication use, limitations in basic or instrumental activities of
      daily living, and cognitive impairment. DATA SYNTHESIS: Eighteen studies met
      inclusion criteria and provided a multivariate analysis including at least 1 of
      the risk factor domains. The estimated pretest probability of falling at least
      once in any given year for individuals 65 years and older was 27% (95% confidence
      interval, 19%-36%). Patients who have fallen in the past year are more likely to
      fall again [likelihood ratio range, 2.3-2.8]. The most consistent predictors of
      future falls are clinically detected abnormalities of gait or balance (likelihood
      ratio range, 1.7-2.4). Visual impairment, medication variables, decreased
      activities of daily living, and impaired cognition did not consistently predict
      falls across studies. Orthostatic hypotension did not predict falls after
      controlling for other factors. CONCLUSIONS: Screening for risk of falling during
      the clinical examination begins with determining if the patient has fallen in the
      past year. For patients who have not previously fallen, screening consists of an
      assessment of gait and balance. Patients who have fallen or who have a gait or
      balance problem are at higher risk of future falls.

PMID- 17200479
TI  - Law as a tool to facilitate healthier lifestyles and prevent obesity.

PMID- 17200481
TI  - JAMA patient page. Meningitis.

PMID- 17200480
TI  - Pexelizumab does not "complement" percutaneous coronary intervention in patients
      with ST-elevation myocardial infarction.

PMID- 17200483
TI  - Diffusion tensor imaging: scientific advance, clinical tool, or just a pretty
      picture?

PMID- 17200484
TI  - Learning to walk: challenges for spinal muscular atrophy clinical trials.

PMID- 17200485
TI  - Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and
      Alzheimer disease.
AB  - BACKGROUND: Neuroimaging in mild cognitive impairment (MCI) and Alzheimer disease
      (AD) generally shows medial temporal lobe atrophy and diminished glucose
      metabolism and cerebral blood flow in the posterior cingulate gyrus. However, it
      is unclear whether these abnormalities also impact the cingulum fibers, which
      connect the medial temporal lobe and the posterior cingulate regions. OBJECTIVE:
      To use diffusion tensor imaging (DTI), by measuring fractional anisotropy (FA),
      to test 1) if MCI and AD are associated with DTI abnormalities in the
      parahippocampal and posterior cingulate regions of the cingulum fibers; 2) if
      white matter abnormalities extend to the neocortical fiber connections in the
      corpus callosum (CC); 3) if DTI improves accuracy to separate AD and MCI from
      healthy aging vs structural MRI. METHODS: DTI and structural MRI were preformed
      on 17 patients with AD, 17 with MCI, and 18 cognitively normal (CN) subjects.
      RESULTS: FA of the cingulum fibers was significantly reduced in MCI, and even
      more in AD. FA was also significantly reduced in the splenium of the CC in AD,
      but not in MCI. Adding DTI to hippocampal volume significantly improved the
      accuracy to separate MCI and AD from CN. CONCLUSION: Assessment of the cingulum
      fibers using diffusion tensor imaging may aid early diagnosis of Alzheimer
      disease.

PMID- 17200486
TI  - Headache and cerebral venous air embolism.

PMID- 17200487
TI  - A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson
      disease.
AB  - OBJECTIVE: To determine if future studies of coenzyme Q(10) and GPI-1485 in
      Parkinson disease (PD) may be warranted. METHODS: We conducted a randomized,
      double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in
      early untreated PD using placebo data from the DATATOP study to establish the
      futility threshold. RESULTS: The primary outcome measure (change in total Unified
      Parkinson's Disease Rating Scale scores over 1 year) did not meet the
      prespecified criteria for futility for either agent. Secondary analyses using
      calibration controls and other more recent placebo data question the
      appropriateness of the predetermined definition of futility, and suggest that a
      more restrictive threshold may be needed. CONCLUSIONS: Coenzyme Q(10) and GPI
      1485 may warrant further study in Parkinson disease, although the data are
      inconsistent. Additional factors (cost, availability of other agents, more recent
      data on placebo outcomes, other ongoing trials) should also be considered in the
      selection of agents for Phase III studies.

PMID- 17200488
TI  - More severe disability of North Africans vs Europeans with multiple sclerosis in
      France.
AB  - OBJECTIVE: To compare the clinical disease progression in European (E) and North
      African (NA) patients with multiple sclerosis (MS) patients in France. METHODS:
      We compared the clinical features of MS in 211 NA patients and 2,945 E patients
      in a French population-based cohort with definite MS according to McDonald's
      criteria. RESULTS: Among the NA patients with MS, 66.4% were women vs 72.9% of
      the E patients (p = 0.04), 15.6% had a primary progressive form of MS vs 11.7% of
      the E patients (p = 0.08), and the mean age at onset was 29.9 +/- 9.8 years in
      the NA patients vs 32.9 +/- 10.6 years in the E patients (p < 0.0001). In the NA
      patients, there was a higher proportion of patients with incomplete recovery from
      the first relapse (p < 0.0001), a shorter time between the first two relapses (p
      = 0.02), a higher number of relapses in the first 5 years (p = 0.03), and a
      shorter time to reach an Expanded Disability Status Scale score of 4.0 (p =
      0.001) or 6.0 (p < 0.0001). The only statistical difference in these factors
      between NA patients born in France and those born in North Africa was the mean
      age at onset of symptoms: it was earlier in NA patients born in France (p <
      0.0001). CONCLUSIONS: The course of multiple sclerosis is more aggressive in
      North African than in European patients.

PMID- 17200489
TI  - Risk of ischemic stroke and lifetime estrogen exposure.
AB  - BACKGROUND: Estrogen loss has been related to higher incidence of stroke in
      postmenopausal women, but randomized trials have demonstrated an increased risk
      of stroke in women receiving hormone replacement therapy (HRT). OBJECTIVE: To
      assess the relationship between exposure to endogenous ovarian hormones and the
      risk of noncardioembolic ischemic stroke. METHODS: We conducted a multicenter,
      age-matched, case-control study in postmenopausal women (case: nonembolic
      ischemic stroke; control: no stroke) comparing duration of ovarian activity or
      lifetime estrogen exposure, which was defined as age at menarche to age at
      menopause. Embolic cardiopathy and unreliable gynecologic data were exclusion
      criteria. Cardiovascular disease risk factors were recorded. The relationships of
      the principal variables to the risk of stroke were assessed using a conditional
      logistic regression analysis. RESULTS: There were 430 cases and 905 controls in
      the study. In the multivariate analysis, hypertension (odds ratio [OR]: 2.73; 95%
      CI: 2.09 to 3.58; p < 0.0001), diabetes (OR: 3.38; 95% CI: 2.53 to 4.52; p <
      0.0001), hyperlipidemia (OR: 1.31; 95% CI: 1.01 to 1.7; p = 0.045), lifespan of
      ovarian activity <34 years (OR: 1.51; 95% CI: 1.13 to 2.03; p = 0.005), and
      menarche at <13 years of age (OR 1.49; 95% CI: 1.15 to 1.92; p = 0.002) were
      independently related to an increased risk of stroke. Obesity (OR: 0.73; 95% CI:
      0.56 to 0.95; p = 0.021) was related to a lower risk of stroke. CONCLUSIONS:
      Longer lifetime exposure to ovarian estrogens may protect against
      noncardioembolic ischemic stroke. However, a very early age of exposure onset
      could be disadvantageous.

PMID- 17200490
TI  - Recanalization after thrombolysis in stroke patients: predictors and prognostic
      implications.
AB  - OBJECTIVE: To estimate rates, predictors, and prognostic importance of
      recanalization in an unselected series of patients with stroke treated with IV
      thrombolysis. METHODS: We performed a CT angiography or transcranial Doppler
      (TCD) follow-up examination 24 hours after IV thrombolysis in 64 patients with
      documented occlusion of the intracranial internal carotid or middle cerebral
      artery (MCA). Complete recanalization was defined by a rating of 3 on the
      Thrombolysis in Myocardial Infarction or 4/5 on the Thrombolysis in Brain
      Ischemia grading scales. Information about risk factors, clinical features, and
      outcome was prospectively collected by standardized procedures. RESULTS: Complete
      recanalization was achieved in 36 of the 64 patients (56.3%). There was a
      nonsignificant trend of recanalization rates to decline with a more proximal site
      of occlusion: 68.4% (M2 segment of MCA), 53.1% (M1 segment), and 46.2% (carotid
      T) (p for trend = 0.28). Frequencies of vessel reopening were markedly reduced in
      subjects with diabetes (9.1% vs 66.0% in nondiabetics, p < 0.001) and less so in
      subjects with additional extracranial carotid occlusion (p = 0.03). Finally,
      complete recanalization predicted a favorable stroke outcome at day 90
      independently of the information provided by age, NIH Stroke Scale, and onset-to
      needle time. CONCLUSIONS: We found a high rate of vessel recanalization after IV
      thrombolysis occlusion. However, recanalization was infrequent in patients with
      diabetes and extracranial carotid occlusion. Information on recanalization was a
      powerful, early predictor for clinical outcome.

PMID- 17200491
TI  - Intraosseous hemangioma in parietal bone.

PMID- 17200493
TI  - Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G
      (MERRF) in tRNALys.
AB  - We describe a patient who presented with parkinsonism associated with the A8344G
      myoclonus epilepsy, ataxia, and myopathy with ragged red fibers mutation in the
      tRNA(Lys) gene. In addition, neurogenic changes and mitochondrial myopathy with
      ragged red fibers were observed. Neither myoclonus epilepsy nor other clinical
      signs described in association with A8344G were noted. Similar to previously
      reported patients with parkinsonism and mtDNA deletions, the symptoms of our
      patient responded favorably to levodopa therapy.

PMID- 17200492
TI  - Zonisamide improves motor function in Parkinson disease: a randomized, double
      blind study.
AB  - OBJECTIVE: To evaluate the efficacy, safety and tolerability of daily doses of
      25, 50, and 100 mg of zonisamide (ZNS) administered as adjunctive treatment in
      patients with Parkinson disease (PD). METHODS: We conducted a multicenter,
      randomized, double-blind, parallel-treatment, placebo-controlled study in Japan.
      Patients with PD who showed insufficient response to levodopa treatment were
      given placebo for 2 weeks and then treated for 12 weeks with 25, 50, or 100
      mg/day of ZNS or placebo, in addition to levodopa, followed by a 2-week dose
      reduction period. The primary endpoint was change from baseline in the total
      score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part III at the
      final assessment point. Secondary endpoints included changes from baseline in
      total daily "off" time; total scores of UPDRS Parts I, II, and IV; and Modified
      Hoehn and Yahr Scale score. Safety analysis was based on the incidence of adverse
      events. RESULTS: There was significant improvement in the primary endpoint in the
      25-mg and 50-mg groups vs placebo. The duration of "off" time was significantly
      reduced in the 50-mg and 100-mg groups vs placebo. Dyskinesia was not increased
      in ZNS groups. The incidence of adverse effects was similar between the 25-mg, 50
      mg, and placebo groups but higher in the 100-mg group. CONCLUSIONS: Zonisamide is
      safe, effective and well tolerated at 25 to 100 mg/day as an adjunctive treatment
      in patients with Parkinson disease.

PMID- 17200494
TI  - Endurance training: an effective and safe treatment for patients with LGMD2I.
AB  - We studied the effect of aerobic training on conditioning in patients with limb
      girdle muscular dystrophy type 2I (LGMD2I). Nine patients with LGMD2I cycled
      fifty 30-minute sessions at 65% of their maximal oxygen uptake over 12 weeks.
      Training significantly improved work capacity, paralleled by self-reported
      improvements. Creatine kinase levels did not increase significantly, and muscle
      morphology was unaffected. Moderate-intensity endurance training is a safe method
      to increase exercise performance and daily function in patients with LGMD2I.

PMID- 17200495
TI  - Cognitive prognosis of patients with tuberous sclerosis complex.
AB  - To assess cognitive outcome in patients with tuberous sclerosis complex (TSC) and
      identify predictive risk factors, we reviewed records of 107 patients who
      underwent comprehensive neuropsychiatric evaluation. Fifty-seven percent of
      patients with TSC had normal-range IQ/developmental quotient (DQ). Cognitive
      outcome was strongly associated with refractory seizures and TSC2 mutation. In
      TSC, IQ/DQ is bimodally distributed, and more than half of individuals are in the
      normal range.

PMID- 17200497
TI  - A 34-year-old man with progressive behavioral and language disturbance.

PMID- 17200496
TI  - Vertebral artery hypoplasia: a predisposing factor for posterior circulation
      stroke?
AB  - We determined in 725 sequentially admitted first-ever stroke patients, using
      color-coded duplex flow imaging of the V2 segment, whether vertebral artery
      hypoplasia (VAH) (diameter < or = 2.5 mm) was more frequent (13%) in posterior
      circulation territory infarction (247) than in strokes in other territories
      (4.6%). This difference is significant (p < 0.001), whereas all other risk
      factors (hypertension, hyperlipidemia, diabetes, smoking) were equally (p > 0.05)
      distributed. Patients with VAH may be predisposed to stroke in the posterior
      circulation.

PMID- 17200499
TI  - Increased incidence of deep venous thrombosis in ALS.

PMID- 17200498
TI  - Objective assessment of bilateral conjunctival injection during cluster headache
      attacks.

PMID- 17200500
TI  - Familial oculoleptomeningeal amyloidosis associated with primary angiitis of the
      CNS.

PMID- 17200501
TI  - The portrayal of coma in contemporary motion pictures.

PMID- 17200502
TI  - Wish to die in end-stage ALS.

PMID- 17200503
TI  - Practice parameter: evaluation and treatment of depression, psychosis, and
      dementia in Parkinson disease (an evidence-based review): report of the Quality
      Standards Subcommittee of the American Academy of Neurology.

PMID- 17200504
TI  - Inhaled corticosteroids for chronic obstructive pulmonary disease: a status
      report.

PMID- 17200505
TI  - Tidal recruitment and overinflation in acute respiratory distress syndrome: yin
      and yang.

PMID- 17200506
TI  - RAGE in lung tumors.

PMID- 17200507
TI  - Study of infliximab treatment in asthma.

PMID- 17200508
TI  - Aging, the aging lung, and senile emphysema are different.

PMID- 17200510
TI  - Should individuals who are tuberculin skin test negative and positive to RD1-IFN
      gamma assay receive preventive therapy?

PMID- 17200512
TI  - Peripheral nerve blocks of the hand.

PMID- 17200513
TI  - Predictive validity of a computerized emergency triage tool.
AB  - BACKGROUND: Emergency department (ED) triage prioritizes patients on the basis of
      the urgency of need for care. eTRIAGE is a Web-based triage decision support tool
      that is based on the Canadian Triage and Acuity Scale (CTAS), a five level triage
      system (CTAS 1 = resuscitation, CTAS 5 = nonurgent). OBJECTIVES: To examine the
      validity of eTRIAGE on the basis of resource utilization and cost as measures of
      acuity. METHODS: Scores on the CTAS, specialist consultations, computed
      tomography use, ED length of stay, ED disposition, and estimated ED and hospital
      costs (if the patient was subsequently admitted to hospital) were collected for
      each patient over a six month period. These data were queried from a database
      that captures all regional ED visits. Correlations between CTAS score and each
      outcome were measured by using logistic regression models (categorical
      variables), univariate analysis of variance (continuous variables), and the
      Kruskal-Wallis analysis of variance (costs). A multivariate regression model that
      used cost as the outcome was used to identify interaction between the variables
      presented. RESULTS: Over the six month study, 29,524 patients were triaged by
      using eTRIAGE. When compared with CTAS level 3, the odds ratios for consultation,
      CT scan, and admission were significantly higher in CTAS 1 and 2 and were
      significantly lower in CTAS 4 and 5 (p < 0.001). When compared with CTAS levels 2
      5 combined, the odds ratio for death in CTAS 1 was 664.18 (p < 0.001). The length
      of stay also demonstrated significant correlation with CTAS score (p < 0.001).
      Costs to the ED and hospital also correlated significantly with increasing acuity
      (median costs for CTAS levels in Canadian dollars: CTAS 1 = 2,690 dollars, CTAS 2
      = 433 dollars, CTAS 3 = 288 dollars, CTAS 4 = 164 dollars, CTAS 5 = 139 dollars,
      and p < 0.001). Significant interactions between the data collected were found in
      a multivariate regression model, although CTAS score remained highly associated
      with costs. CONCLUSIONS: Acuity measured by eTRIAGE demonstrates excellent
      predictive validity for resource utilization and ED and hospital costs. Future
      research should focus on specific presenting complaints and targeted resources to
      more accurately assess eTRIAGE validity.

PMID- 17200514
TI  - The financial impact of ambulance diversions and patient elopements.
AB  - OBJECTIVES: Admission process delays and other throughput inefficiencies are a
      leading cause of emergency department (ED) overcrowding, ambulance diversion, and
      patient elopements. Hospital capacity constraints reduce the number of treatment
      beds available to provide revenue-generating patient services. The objective of
      this study was to develop a practical method for quantifying the revenues that
      are potentially lost as a result of patient elopements and ambulance diversion.
      METHODS: Historical data from 62,588 patient visits to the ED of a 450-bed
      nonprofit community teaching hospital in central Pennsylvania between July 2004
      and June 2005 were used to estimate the value of potential patient visits
      foregone as a result of ambulance diversion and patients leaving the ED without
      treatment. RESULTS: The study hospital may have lost 3,881,506 dollars in net
      revenue as a result of ambulance diversions and patient elopements from the ED
      during a 12-month period. CONCLUSIONS: Significant revenue may be foregone as a
      result of throughput delays that prevent the ED from utilizing its existing bed
      capacity for additional patient visits.

PMID- 17200515
TI  - Pitfalls in the diagnosis of cerebellar infarction.
AB  - BACKGROUND: Cerebellar infarctions are an important cause of neurologic disease.
      Failure to recognize and rapidly diagnose cerebellar infarction may lead to
      serious morbidity and mortality due to hydrocephalus and brain stem infarction.
      OBJECTIVES: To identify sources of preventable medical errors, the authors
      obtained pilot data on cerebellar ischemic strokes that were initially
      misdiagnosed in the emergency department. METHODS: Fifteen cases of misdiagnosed
      cerebellar infarctions were collected, all seen, or reviewed by the authors
      during a five-year period. For each patient, they report the presenting symptoms,
      the findings on neurologic examination performed in the emergency department,
      specific areas of the examination not performed or documented, diagnostic
      testing, the follow-up course after misdiagnosis, and outcome. The different
      types of errors leading to misdiagnosis are categorized. RESULTS: Half of the
      patients were younger than 50 years and presented with headache and dizziness.
      All patients had either incomplete or poorly documented neurologic examinations.
      Almost all patients had a computed tomographic scan of the head interpreted as
      normal, and most of these patients underwent subsequent magnetic resonance
      imaging showing cerebellar infarction. The initial incorrect diagnoses included
      migraine, toxic encephalopathy, gastritis, meningitis, myocardial infarction, and
      polyneuropathy. The overall mortality in this patient cohort was 40%. Among the
      survivors, about 50% had disabling deficits. Pitfalls leading to misdiagnosis
      involved the clinical evaluation, diagnostic testing, and establishing a
      diagnosis and disposition. CONCLUSIONS: This study demonstrates how the diagnosis
      of cerebellar infarction can be missed or delayed in patients presenting to the
      emergency department.

PMID- 17200516
TI  - An ideal model for out-of-hospital airway management?

PMID- 17200519
TI  - 2006: signaling breakthroughs of the year.
AB  - With nominations from leading scientists studying cell signaling, the STKE
      editors compile a list of the year's most important advances. Signaling
      breakthroughs included molecules and processes both outside cells and inside
      cells, from channels in the membrane to chromatin in the nucleus. The nominated
      research ranged from structural and functional revelations to approaches for the
      global analysis of signaling pathways. Receptors were highlighted with unexpected
      proteins functioning as receptors, as well as surprising functions for known
      receptors. This year also brought new insights into the impact of cell signaling
      on human physiology and disease.

PMID- 17200521
TI  - Sub-capital hip fracture: best treatment options.

PMID- 17200520
TI  - How do microRNAs regulate gene expression?
AB  - Several thousand human genes, amounting to about one-third of the whole genome,
      are potential targets for regulation by the several hundred microRNAs (miRNAs)
      encoded in the genome. The regulation occurs posttranscriptionally and involves
      the approximately 21-nucleotide miRNA interacting with a target site in the mRNA
      that generally has imperfect complementarity to the miRNA. The target sites are
      almost invariably in the 3'-untranslated region of the messenger RNA (mRNA),
      often in multiple copies. Metazoan miRNAs were previously thought to down
      regulate protein expression by inhibiting target mRNA translation at some stage
      after the translation initiation step, without much effect on mRNA abundance.
      However, recent studies have questioned these suppositions. With some targets, an
      increase in the rate of mRNA degradation by the normal decay pathway contributes
      to the decrease in protein expression. miRNAs can also inhibit translation
      initiation, specifically the function of the cap-binding initiation factor,
      eIF4E. Repressed target mRNAs as well as miRNAs themselves accumulate in
      cytoplasmic foci known as P-bodies, where many enzymes involved in mRNA
      degradation are concentrated. However, P-bodies may also serve as repositories
      for the temporary and reversible storage of untranslated mRNA, and reducing the
      expression (knockdown) of several distinct P-body protein components can
      alleviate miRNA-mediated repression of gene expression.

PMID- 17200522
TI  - Treatment for unstable intertrochanteric fractures in elderly patients: internal
      fixation versus cone hemiarthroplasty.
AB  - PURPOSE: To evaluate the effectiveness of internal fixation versus cone
      hemiarthroplasty for the treatment of unstable intertrochanteric fractures in
      elderly patients. METHODS: The choice of treatment was based on the year of
      admission: between 2001 and 2003, 42 patients (mean age, 73 years) underwent cone
      hemiarthroplasty using a cementless press fit through a posterior approach,
      whereas between 1999 and 2001, 45 patients (mean age, 75 years) underwent
      internal fixation using a dynamic hip screw through a lateral approach in a
      supine position. Patients with stable fractures with intact lesser trochanter,
      immobility before injury, age younger than 60 years, or with associated injuries
      (such as another fracture) were excluded. Patients were encouraged active
      rehabilitation in bed. Bony union was determined by clinical and radiological
      examinations. Patients were followed up at 6-week intervals in the first sixth
      months and every 3 months thereafter until bony union was achieved. In the final
      follow-up, 32 cone hemiarthroplasty patients and 38 internal fixation patients
      were available for evaluation according to Merle d'Aubigne and Postel criteria.
      RESULTS: There were no significant differences between the 2 groups in terms of
      sex, age, fracture type, Singh index, follow-up period, hospital stay, operating
      time, and receipt of blood transfusions. Clinical results of both groups were
      similar. Hemiarthroplasty patients were allowed full weight bearing significantly
      earlier than the internal fixation patients. CONCLUSION: Cone hemiarthroplasty
      can be an alternative treatment for unstable intertrochanteric fractures in
      elderly patients so as to achieve earlier mobilisation.

PMID- 17200523
TI  - Elderly patients with two episodes of fragility hip fractures form a special
      subgroup.
AB  - PURPOSE: To identify the demographic features of patients aged 65 years or older
      admitted with 2 episodes of fragility hip fractures. METHODS: From July 2003 to
      December 2004 inclusive, 50 consecutive elderly patients underwent surgery for a
      second episode of hip fracture. Patients in a very poor physical condition and
      therefore unfit for surgery were excluded. Risk factors of fractures in both
      episodes and whether risk factors were corrected after the first episode were
      analysed. Detailed radiological assessment and charting of elderly mobility
      scores and Barthel index were completed and the one-year mortality rate
      documented. The rehabilitation periods for the 2 episodes of hip fracture were
      compared. RESULTS: Most patients were female and had trochanteric fractures. In
      patients aged 65 to 75 years, the incidence of femoral neck fracture occurred as
      often as trochanteric fracture; while trochanteric fracture was predominant in
      older patients. Subclinical osteomalacia and undiagnosed hyperthyroidism was
      found in 3 of the 7 younger patients. Only 30% of them were on treatment for
      osteoporosis after the first fracture, which underlines the importance of
      osteoporosis treatment in these patients. CONCLUSION: Elderly patients with 2
      episodes of fragility hip fractures form a special subgroup among geriatric hip
      fracture patients. Fall prevention programmes and treatment for osteoporosis are
      recommended.

PMID- 17200524
TI  - Intra-operative error during Austin Moore hemiarthroplasty.
AB  - PURPOSE: To examine the frequency of technical errors during implantation of the
      Austin Moore prosthesis in a public hospital. METHODS: Radiographs and charts of
      147 consecutive uncemented Austin Moore hemiarthoplasty patients were
      retrospectively reviewed with particular reference to intra-operative errors
      associated with early failure of the prosthesis. RESULTS: 48% of the patients had
      at least one error pertinent to implantation and 14% sustained intra-operative
      fractures. The error rates between relatively junior doctors and consultants were
      not significantly different. CONCLUSION: The uncemented Austin Moore prosthesis
      is a technically demanding prosthesis that is difficult to implant well. Greater
      selectivity should be exercised when considering its use for femoral neck
      fractures.

PMID- 17200525
TI  - Retrograde nailing for distal third femoral shaft fractures: a prospective study.
AB  - PURPOSE: To evaluate the postoperative knee function and results of unreamed
      retrograde nailing for distal third femoral shaft fractures. METHODS: Between
      January 2002 and 2003 inclusive, a consecutive series of 27 patients (with 28
      fractures) who underwent retrograde nailing were prospectively evaluated. Outcome
      measures were union time, initiation of weight bearing, deformity and shortening,
      functional length of the nail, knee function assessed using a modified Knee
      Society Knee Score. Correlations between union time and other variables were also
      studied. RESULTS: In these patients 26 (93%) of the 28 fractures achieved union,
      of which 5 underwent dynamisation; the mean union time for the other 21 fractures
      was 4.4 months. Angular malalignment was present in 4 patients and shortening in
      4 others. There was negligible correlation between union time and variables of
      nail-canal diameter mismatch, functional length of nail, fracture geometry, or
      initiation of partial weight bearing ambulation. Knee flexion of more than 100
      degrees was achieved in 26 patients. 19 patients had anterior knee pain and 10
      had instability. By the end of one year, excellent or good scores for pain and
      function were recorded in 77% and 73% respectively, of the 26 patients.
      CONCLUSION: In view of such favourable union rates but significant deterioration
      in overall knee joint function, at best retrograde nailing is a reliable
      alternative in the management of selected complicated fractures of the distal
      femoral shaft.

PMID- 17200526
TI  - One-stage combined surgery with or without preoperative traction for
      developmental dislocation of the hip in older children.
AB  - PURPOSE: To compare one-stage combined surgery with and without preoperative
      traction, in older children with developmental dislocation of the hip (DDH).
      METHODS: Records of 9 children who underwent combined surgery for DDH with
      preoperative traction in 12 hips (group 1) and 12 undergoing the same procedure
      without preoperative traction in 16 hips (group 2) were retrospectively reviewed.
      The surgery consisted of open reduction, Salter's innominate osteotomy and
      femoral shortening with derotation varus osteotomy. The mean age of the patients
      at the time of operation was 5.8 years. The mean follow-up period was 5.9 years.
      RESULTS: At final follow-up, clinical outcome in group 1 was worse than that in
      group 2, though radiographic assessment demonstrated no significant difference
      between the groups. CONCLUSION: One-stage combined surgery without preoperative
      traction is effective in the treatment of DDH in older children, and has a lower
      complication rate, but radiographically the groups did not differ.

PMID- 17200527
TI  - Modified Ilizarov technique for infected nonunion of the femur: the principle of
      distraction-compression osteogenesis.
AB  - PURPOSE: To evaluate the treatment outcome of the modified Ilizarov technique in
      infected nonunion of the femur. METHODS: Between 1989 and 2002, records of 20
      patients with infected nonunion of the femur treated with the modified Ilizarov
      technique were retrospectively reviewed. The modified Ilizarov frame was fixed
      after necrectomy of the dead infected bone and tissues. A proximal or distal
      corticotomy was performed following biological principles. For regeneration of
      gap, segmental transport was performed in 11 patients with a gap of more than 5
      cm; acute docking followed by lengthening at the corticotomy site was performed
      in 9 patients with a gap of smaller than 5 cm. Mobilisation was started early
      with active participation of the physical therapist and the patients. Bone and
      functional results were measured and complications were categorised according to
      the Association for the Study and Application of the Method of Ilizarov
      guidelines. RESULTS: The mean follow-up period was 62.8 months. Bony union and
      eradication of the infection was achieved in all patients except one who
      underwent amputation due to uncontrolled infection. Bone results were excellent
      in 13 patients, good in 4, fair in one, poor in one, and treatment failure
      (amputation) in one. Functional results were excellent in 3 patients, good in 9,
      fair in 3, poor in 4, and failure in one. A total of 71 complications occurred:
      35 problems, 6 obstacles, and 30 true complications. The mean healing index was
      38.3 day/cm (standard deviation, 1.6 day/cm). CONCLUSION: The Ilizarov technique
      is a good salvage operation for infected nonunion of the femur. Limb salvage is
      preferable to prosthesis if the limb is viable, adequately innervated and the
      patient is mentally and financially committed to save the limb.

PMID- 17200528
TI  - Acute compression and lengthening by the Ilizarov technique for infected nonunion
      of the tibia with large bone defects.
AB  - PURPOSE: To assess the Ilizarov technique in treating large infected tibial
      defects by resection of the infected focus, its acute compression, and gradual
      distant site lengthening. METHODS: 27 men (mean age, 39 years) with infected
      nonunion and large bone defects of the tibia underwent complete resection of the
      nonunion site, debridement, sequestrectomy, lavage, and Ilizarov ring fixator
      application. Patients underwent acute compression of the defect site, followed by
      distant site metaphyseal corticotomy for simultaneous lengthening. The mean
      length of resection was 10 (range, 6-17) cm. The mean follow-up was 27 (range, 25
      39) months. RESULTS: The mean lengthening achieved was 10 cm, mean union time 6.3
      months, and mean duration of consolidation 10.2 months. Functional results were
      excellent in 19 patients and good in 5. The union time was longer in older
      patients. CONCLUSION: Acute compression and simultaneous lengthening can be used
      safely for treatment of large bone defects in the tibia. This avoids secondary
      operations at the docking site and reduces the duration of treatment.

PMID- 17200529
TI  - Complex regional pain syndrome complicating total knee arthroplasty.
AB  - PURPOSE: To compare the long-term outcome of patients diagnosed with complex
      regional pain syndrome-type 1 (CRPS-1) after total knee arthroplasty (TKA) with
      those of uncomplicated TKA knees and preoperative osteoarthritic knees. METHODS:
      Medical records of 1280 patients who underwent TKA for osteoarthritis were
      retrospectively reviewed; 8 were diagnosed as having symptoms and signs
      consistent with CRPS after TKA. Patients with primary inflammatory arthritis,
      signs of component loosening, malpositioning, or of infected arthroplasty were
      excluded. No patient had signs of CRPS prior to operative intervention. The 8
      patients were compared with 2 groups of age- and sex-matched controls:
      uncomplicated TKA knees and preoperative osteoarthritic knees. Patients were
      followed up for a mean of 54 (range, 13-111) months and their range of movement,
      Western Ontario and McMaster Universities Osteoarthritis Index, SF-36
      questionnaire scores, and Knee Society scores were assessed and compared.
      RESULTS: After appropriate treatment, most CRPS complicated patients had similar
      scores on SF-36, Western Ontario and McMaster Universities Osteoarthritis Index,
      and Knee Society scores when compared with uncomplicated TKA patients. Scores for
      CRPS complicated patients were significantly improved when compared with
      preoperative osteoarthritic patients. The incidence of CRPS after TKA was 0.7%.
      CONCLUSION: When managed early, patients complicated with CRPS after TKA have a
      similar prognosis to patients with uncomplicated TKA.

PMID- 17200530
TI  - Diagnosis of post-traumatic complex regional pain syndrome of the hand: current
      role of sympathetic skin response and three-phase bone scintigraphy.
AB  - PURPOSE: To evaluate the role of sympathetic skin response (SSR) and three-phase
      bone scintigraphy (TPBS) in the diagnosis of complex regional pain syndrome
      (CRPS). METHODS: 60 patients with CRPS of the hand were recruited. TPBS was
      performed using a bolus injection of 20 mCi of Tc-99m methylene diphosphonate in
      an antecubital vein and blood flow (first phase) image, blood pool (second phase)
      image, and delayed (third phase) image obtained. Patients were considered to have
      CRPS when the blood pool and blood flow images showed diffuse asymmetric uptake,
      or when the delayed image indicated increased asymmetric periarticular uptake.
      SSR was measured simultaneously in the affected and unaffected hands. Standard
      surface electromyogram disc electrodes were applied to the palm and dorsum of
      both hands. Electrical stimuli were applied to the skin at the base of little and
      ring fingers of the unaffected hand. Patients were considered abnormal when
      response was absent or the peak-to-peak amplitude was <50% of the contralateral
      hand in at least 2 readings. RESULTS: The delayed phase of TPBS tested positive
      in all; the first and second phases tested positive in 54 (90%) and 56 (93%) of
      the patients, respectively. Four of the 6 patients with a negative first phase
      had had symptoms persisting for more than 6 months, and the other 2 for about 3
      to 6 months. No patient presenting within 3 months had a negative scan. SSR was
      absent in 16 (27%) patients and normal in 44 (73%). 11 (79%) of 14 patients who
      presented more than 6 months after symptom onset displayed an abnormal SSR, while
      only 10% of those presenting within 3 to 6 months and 11% of those presenting
      within 3 months had an abnormal SSR. 12 (75%) of the 16 patients with abnormal
      SSR had associated decreased sweating, compared with 2 (4.5%) of the 44 patients
      with a normal SSR. CONCLUSION: TPBS is a very sensitive corroborative test to
      confirm the clinical suspicion of CRPS during the initial stages, but not in late
      cases. SSR can be used to document the sympathetic dysfunction in cases having an
      associated sweating abnormality and may have some diagnostic value in late cases
      of CRPS, when TPBS is less reliable.

PMID- 17200531
TI  - Locking compression plate in the treatment of forearm fractures: a prospective
      study.
AB  - PURPOSE: To evaluate the use of locking compression plates (LCPs) in diaphyseal
      forearm fractures. METHODS: 9 women and 23 men (mean age, 35; range, 12-70 years)
      with 45 forearm fractures were treated by open reduction and internal fixation
      with 3.5-mm stainless steel LCPs. All patients were followed up monthly until
      union; the mean duration being 20 months. Radiographic assessment was performed
      at 3, 6, 12, and 18 months. Clinical assessments regarding pain and function were
      undertaken at the final follow-up. RESULTS: Two patients had delayed union but
      none had nonunion. There was no deep infection and only one superficial
      infection. Two refractures occurred after implant removal, both were of simple
      transverse type and at the sites of the original fractures. 33% of the fractures
      were reduced anatomically. 56% of the fractures healed with no or minimal callus
      formation and 44% with moderate callus formation. In total, 13% of the
      anatomically reduced fractures had moderate or abundant callus formation. 22
      patients opted for removal of the implants (29 LCPs), after a mean of 16 (range,
      9-21) months. CONCLUSION: The LCP is an effective bridging device used for
      treating comminuted fractures, but for treating simple fractures its superiority
      over conventional plating is yet to be proven.

PMID- 17200532
TI  - Thumb polydactyly: clinical outcome after reconstruction.
AB  - PURPOSE: To evaluate clinical and cosmetic outcomes of reconstruction in thumb
      polydactyly and prognostic value of the Wassel classification. METHODS: Between
      1993 and 2000 inclusive, out of the patients with thumb polydactyly (involving 80
      thumbs) operated on, 34 patients (36 thumbs) were available for review and
      underwent clinical and radiological assessment. Outcomes in terms of the Tada
      score and complications were recorded. RESULTS: The mean age of patients at the
      time of operation was 2.8 (range, 0.6-47) years. The mean follow-up period was 5
      (range, 2.4-10) years. According to the Wassel classification, 12 were type-II
      thumb polydactyly, 3 type-III, 11 type-IV, 6 type-V, one type-VI, and 3 type-VII.
      There was no perioperative mortality or wound infection. More than 88% of the
      patients were satisfied or very satisfied with functional and cosmetic outcomes.
      Postoperative complications such as scar hypertrophy, pulp atrophy, joint
      deformity, and instability were common but minor. Ridge nail deformity after the
      Bilhaut Cloquet procedure was amenable to secondary corrective procedures. All
      types of operated thumb polydactyly achieved similar mean Tada scores (14.7- 16.6
      out of 20). The Wassel classification category, age, and surgical procedures were
      found to have no prognostic value with regard to the Tada score and presence of
      complications. CONCLUSION: Surgery on thumb polydactyly is rewarding. The Wassel
      classification category can be used as a guide for treatment, although it fails
      to predict the occurrence of postoperative complications or Tada scores. Our
      patients' results can serve as guidelines of expected outcomes after
      reconstructive procedures in different sub-types of thumb polydactyly.

PMID- 17200533
TI  - Morphological adaptation of the bone graft and fused bodies after non
      instrumented anterior interbody fusion of the lower cervical spine.
AB  - PURPOSE: To assess the remodelling process of the bone graft and fused bodies
      after non-instrumented anterior interbody fusion with autogenous iliac graft in
      patients with spondylosis, infections, fractures, or disorders of the cervical
      spine. METHODS: 68 patients aged 18 to 58 years who underwent non-plated anterior
      lower cervical interbody fusion with an iliac graft were retrospectively studied.
      Diagnoses of the patients were degenerative disc diseases (n=32), disc herniation
      (n=15), fractures (n=13), and tuberculosis (n=8). The Robinson and Smith
      technique was used to treat degenerative disc diseases and protruded disc, and
      the Bailey and Badgley procedure for fractures or tuberculosis of the cervical
      spine. 34, 25, and 9 patients underwent one-, 2-, and 3-segment fusions,
      respectively. 18 of the 25 patients underwent two-segment fusion with a single
      large bone block, and 7 with 2 separate bone blocks for each segment. Four of the
      9 patients underwent three-segment fusion with a single large bone block, and 5
      used separate grafts for each segment independently. Plain and stress radiography
      was primarily used to assess the fusion. Computed tomography and magnetic
      resonance imaging were also used in some patients. Some anterior graft extrusion
      (amounting to less than 10% of corresponding anteroposterior body width) was used
      to observe the remodelling during graft-take and thereafter. Postoperative
      cervical traction for 2 to 4 weeks, then cervical collar immobilisation for 4 to
      12 weeks were strictly followed according to the numbers of fused segments. A
      halo vest was applied in 4 patients with fracture undergoing 3-segment fusion as
      they could not tolerate the prolonged bed rest or rigid cervical brace. RESULTS:
      The mean time for the graft to fuse was 8.6 (range, 7-14) weeks in patients who
      underwent each segment fusion with independent free grafts, and 10 and 14 weeks
      in those who underwent 2- and 3-segment single large graft fusion, respectively.
      The final loss of disc height and joint angle were negligible, regardless of the
      extent of fusion. Bony absorption of the anteriorly protruded part of the graft
      began at postoperative week 10 (range, 6-28), which coincided with the time of
      graft-take and initiation of remodelling. CONCLUSION: The earliest sign of bony
      absorption of the anteriorly protruded part of the graft indicated the initiation
      of the graft-take and the graft remodelling. The inwaisting sign of the
      surgically fused block of vertebral bodies was a morphological adaptation.
      Despite the altered biomechanics of the spine in the fused area, the inwaisting
      sign indicated maintenance of normal function at the parafusion motion segments.

PMID- 17200534
TI  - One-stage lateral rhachotomy and posterior spinal fusion with compression hooks
      for Pott's paralysis in the elderly.
AB  - PURPOSE: To evaluate the safety and effectiveness of one-stage lateral rhachotomy
      and posterior fusion with compression hooks, for the treatment of Pott's
      paralysis in the elderly. METHODS: 11 elderly patients underwent lateral
      rhachotomy (costotransversectomy and pediculectomy) to debride the tuberculosis
      focus extending into the epidural space and to decompress the spinal cord. After
      debridement, the interbody cavity was packed with autologous iliac bone chips.
      For stabilisation, posterior fusion was performed using a compression lamina hook
      system. Patients were followed up for at least 2 years for complications.
      Neurological status was assessed using the Frankel score. The kyphotic deformity
      was measured on lateral radiographs taken before surgery and at follow-up.
      RESULTS: During separation of the adhesion around the abscess, a dural tear
      occurred in one patient and a pleural tear in another. Both tears were
      successfully repaired. One patient had mild pneumonia after surgery. The Frankel
      scores of the 11 patients improved from C or D before surgery to D or E after
      surgery. No relapse of spinal tuberculosis was encountered. The mean deformity
      angle was 25.5 degrees before surgery and 23.2 degrees at the final follow-up.
      Spinal fusion was achieved in all patients. CONCLUSION: Without the need of
      thoracotomy, one-stage lateral rhachotomy with posterior spinal fusion using
      compression hooks was an effective option for treating Pott's paralysis in the
      elderly.

PMID- 17200535
TI  - Biocompatability of hydroxyapatite composite as a local drug delivery system.
AB  - PURPOSE: To investigate the biocompatibility of hydroxyapatite composite
      (hydroxyapatite, plaster of Paris, and chitosan) impregnated with gentamicin,
      fosfomycin, imipenem, or amphotericin B. METHODS: The interactions of the extract
      from each drug against osteoblast were tested using the methylthiotetrazole test.
      RESULTS: Extracts from all drugs showed good biocompatibility at concentrations
      varying from 10 microgram/ml to 1000 microgram/ml. Imipenem and amphotericin B at
      a concentration of 1000 microgram/ml had a significantly higher percentage of
      cell viability than the control group. No morphological change of osteoblast was
      observed in all drug tests at any concentrations. CONCLUSION: The hydroxyapatite
      composite had a good biocompatibility for carrying gentamicin, fosfomycin,
      imipenem, or amphotericin B.

PMID- 17200536
TI  - Comminuted simultaneous bilateral tibial tubercle avulsion fractures: a case
      report.
AB  - A 16-year-old male had simultaneous bilateral tibial tubercle avulsion fractures
      after making a sudden stop while running at full speed. The left knee injury
      (type V) was minimally displaced, was treated conservatively with closed
      reduction, and the patient recovered uneventfully. The right tibial tubercle
      injury was unusual. The tuberosity and anterior aspect of the proximal epiphysis
      remained as one, but there was severe intra-articular comminution posterior to
      the displaced tubercle fragment. The right knee injury (type III) required open
      reduction and internal fixation to reduce the apophyseal fragment and 2 intra
      articular displaced fragments. The patient's recovery was complicated by a
      severe, persistent flexion deformity on the right side. Eventually, the patient
      required manipulation under anaesthesia, extensive continuous passive
      mobilisation and a turnbuckle extension splint. A residual 5-degree flexion
      deformity remained at 16 months post-injury. This case highlights the importance
      of identifying any intra-articular fragments, their careful anatomical reduction,
      and aggressive mobilisation when treating tibial tubercle avulsion fractures.

PMID- 17200537
TI  - Concomitant ipsilateral traumatic dislocation of the hip and knee following high
      energy trauma: a case report.
AB  - Traumatic dislocation of the hip or knee can occur after high-energy trauma and
      is often associated with concomitant injuries and secondary complications.
      Concomitant traumatic dislocation of both hip and knee is rare. We describe a
      case of combined ipsilateral posterior hip dislocation with a posterior
      acetabular fracture and a complete open knee dislocation with disruption of the
      popliteal artery that resulted in amputation.

PMID- 17200538
TI  - Osteonecrosis of the medial tibial plateau: a case report.
AB  - Medial tibial plateau osteonecrosis is a disease that lacks distinguishing signs
      and symptoms, especially in the early stage, and requires clinicians to exercise
      a high degree of suspicion to prevent disease progression. We present a case of
      spontaneous osteonecrosis of the medial tibial plateau in a 59-year-old woman.
      Within 5 months of the onset of symptoms, the entire medial tibial plateau
      collapsed down into the metaphyseal region, causing severe varus deformity,
      instability, and inability to walk without crutches and a hinged knee brace.
      Initial symptoms of medial joint line pain and generalised swelling of the knee
      were attributed to early degenerative changes. Subsequent radiographs were
      misinterpreted as simple medial compartment arthritis. Due to severe bone loss
      and significant lateral collateral ligament attenuation, a total joint
      arthroplasty was required, using a stemmed tibial component with medial metal
      block and bone graft augmentation. The speed of bone collapse and the extension
      into the metaphysis, requiring complex joint arthroplasty, makes this case
      unique.

PMID- 17200539
TI  - Osteonecrosis of the femoral head caused by bone marrow blockage: a case report.
AB  - Interruption of the blood flow may occur in intra-osseous arteries within the
      femoral head. We report a 72-year-old woman who developed osteonecrosis of the
      femoral head 11 months after surgery involving massive cementing of a segmental
      distal femoral rotating hinge prosthesis to treat nonunion of the distal femur.
      The bone cement filled the cavity up to the femoral neck and the superolateral
      portion of the femoral head, blocking the bone marrow.

PMID- 17200540
TI  - Fixation failure of the clavicular hook plate: a report of three cases.
AB  - Open reduction and internal fixation for unstable fractures of the lateral end of
      the clavicle (Neer type II) is not complication-free. Most clavicle fractures can
      be successfully treated by conservative methods. Neer type II fractures have a
      reportedly high rate of nonunion, therefore internal fixation is recommended.
      However, the need for surgical treatment remains controversial as nonunion seldom
      produces a poor functional outcome. We report 3 cases of fixation failure
      following treatment with a clavicular hook plate. None of the patients required
      re-fixation surgery and all achieved bony union with a good functional result.

PMID- 17200541
TI  - Closed reduction for traumatic posterior dislocation of the shoulder using the
      'lever principle': two case reports and a review of the literature.
AB  - Traumatic posterior dislocation of the shoulder is frequently missed because of
      its rarity and the absence of characteristic symptoms. Several signs should be
      emphasised: an overlap of the humeral head and glenoid rim in a true
      anteroposterior view and the light-bulb sign in the anteroposterior view. To make
      an accurate and early diagnosis, use of multidirectional radiographs combined
      with computed tomography is recommended. Closed reduction was successfully
      performed under general anaesthesia using the DePalma method with slight
      modification--the lever principle--by pushing the medial side of the upper arm
      laterally to adduct the shoulder as far as possible. The dynamics of the lever
      principle make it a safer and more effective method of achieving a closed
      reduction of a posterior dislocation of the shoulder than the conventional method
      of solely pushing the humeral head anteriorly, especially in patients with
      locking of the glenohumeral joint and impression fractures.

PMID- 17200542
TI  - Intraosseous epidermoid cyst of the finger phalanx: a case report.
AB  - Epidermoid cysts of the finger phalanx are rare pseudotumours. They are benign
      lesions with a satisfactory outcome after excision. We describe a case of an
      epidermoid cyst in the distal phalanx of the ring finger. It was treated
      successfully and the patient had excellent functional results and radiological
      healing at one-year follow-up.

PMID- 17200543
TI  - True digital artery aneurysm of the ring finger: a case report.
AB  - True aneurysms of the digital artery are very rare. Only 13 cases, caused by
      chronic trauma from occupational or sports-related overuse, have been reported.
      We present the first case of a true aneurysm of the digital artery of the left
      ring finger caused by chronic repetitive trauma from a wedding ring. The patient
      was a 44-year-old teacher who presented with a 1.5-cm subcutaneous mass on the
      radial aspect of the proximal phalanx of the finger, just proximal to the
      proximal interphalangeal joint. Exploration of the mass revealed a 1-cm aneurysm
      continuous with the radial digital artery. The aneurysm was excised and the
      proximal and distal ends of the radial digital artery ligated. Microscopic
      examination of the excised specimen confirmed the diagnosis of a true aneurysm
      with the lumen filled with an organising thrombus. The patient had an uneventful
      recovery with good wound healing, intact sensation, and normal capillary return.

PMID- 17200544
TI  - Severe scoliosis associated with Costello syndrome: a case report.
AB  - Costello syndrome is characterised by dwarfism, unique cutaneous lesions, a
      distinct facial gestalt, and mental retardation. There have been no detailed
      reports of severe spinal deformities requiring surgical treatment as a
      complication of Costello syndrome. We report a case of a 10-year-old girl with
      progressive scoliosis associated with Costello syndrome. She underwent anterior
      release and posterior surgical correction and fusion from T5 to L2 using a third
      generation hook and rod system plus spinous process wiring. Congenital portal
      vein deficiency and coagulopathy were other major complications. At 15-month
      follow-up, the patient had good balance and no evidence of instrumentation
      failure.

PMID- 17200545
TI  - Tarsal tunnel syndrome caused by a talocalcaneal joint amyloidoma in a long-term
      haemodialysis patient: a case report.
AB  - We present a case of tarsal tunnel syndrome caused by an amyloidoma arising from
      the talocalcaneal joint in a 64-year-old man with a long history of
      haemodialysis. He presented with numbness in the medial plantar area of the right
      foot without any antecedent trauma. The numbness was minimal at rest but
      gradually worsened, causing difficulty, when walking. Paraesthesia was present on
      the medial sole of the right foot. A positive Tinel-like sign was noted 2.5 cm
      below the medial malleolus. Magnetic resonance imaging demonstrated a round
      lesion, 1 cm in diameter, in the calcaneus, which was hypointense on T1-weighted
      images and hyperintense on T2-weighted images. In addition, a mass, 1 cm in
      diameter with a signal isointense to that of muscle was found adjacent to the
      talocalcaneal joint. The medial plantar nerve was decompressed after removing a
      solid, 1-cm diameter mass from the talocalcaneal joint. At 6 months post surgery,
      the numbness had completely resolved. No recurrence was observed at the 24-month
      follow-up.

PMID- 17200546
TI  - Fracture of the os trigonum: a case report.
AB  - The os trigonum is an inconsistently present accessory bone of the foot situated
      at the posterolateral aspect of the talus. It may be radiographically confused
      with fractures of the posterior process of the talus. Fracture of the os trigonum
      per se is extremely rare. Hyperplantarflexion of the ankle is the mechanism of
      injury in which the os trigonum is compressed between the posterior malleolus of
      the tibia and the tuber calcaneus. Computed tomography is the choice of imaging
      modality in cases where fractures of posterior talus structures, including the os
      trigonum, are suspected. A high index of suspicion is necessary to diagnose a
      fracture of the os trigonum after a severe plantarflexion injury to the ankle.
      Conservative treatment is usually successful. We report a case of a fracture of
      the os trigonum, its clinical features, treatment and significance.

PMID- 17200547
TI  - Isolated dorsal midtarsal (Chopart) dislocation: a case report.
AB  - A case of isolated dorsal midtarsal (Chopart) dislocation resulting from blunt
      trauma is reported. The mechanism of injury, management, and long-term outcome
      are discussed. A 45-year-old inebriated man fell from a 4-m height and landed on
      his feet. He had immediate bilateral foot and back pain. Radiographs showed a
      burst fracture of the second lumbar vertebra, a left Pott's fracture, and an
      isolated dorsal dislocation of the right midtarsal (Chopart) joint. No
      neurovascular deficits or signs of compartment syndrome were noted. The image
      intensifier showed the unstable midtarsal joint with dorsal translation of the
      navicular and cuboid from the talus and calcaneum, respectively. Closed reduction
      of the midtarsal joint was performed with 2 transfixing 3.5-mm AO cortical
      screws. The right foot was immobilised in a short leg cast for 6 weeks; screws
      were removed 14 weeks later. At 76-month follow-up, the patient had returned to
      work as a construction worker, but still had right midfoot pain on prolonged
      walking or standing, because of persistent plantar opening up and dorsal
      ossification of the midtarsal joints and degenerative change at the talonavicular
      joint. With hindsight, open reduction may have led to a better outcome through
      repair of the plantar ligamentous structures, especially the plantar
      calcaneonavicular (spring) ligament.

PMID- 17200548
TI  - Letter to the Editor: Pseudomalignant myositis ossificans mimicking osteosarcoma:
      a case report.

PMID- 17200549
TI  - Analysis of protein phosphatases: toolbox for unraveling cell signaling networks.
AB  - Protein phosphatases reverse the covalent modifications of numerous cellular
      proteins imposed by the activation of protein kinases. Although protein
      phosphatases generally demonstrate broader substrate specificity than protein
      kinases, at least in vitro, these enzymes have evolved complex mechanisms to
      target specific physiological substrates and respond to physiological stimuli to
      control numerous physiological events. This chapter provides a brief overview of
      the challenges that faced researchers in protein phosphatases in years past and
      highlights numerous state-of-the-art techniques (described in greater detail in
      other chapters in this volume) available to today's scientists. These methods
      should equip investigators with a rich toolbox of reagents and techniques and
      promise a brighter future for the study of eukaryotic protein phosphatases. These
      experimental approaches should also facilitate future investigations directed at
      unraveling the role of phosphatases in signaling networks in human health and
      disease.

PMID- 17200550
TI  - A brief introduction to the protein phosphatase families.
AB  - This chapter introduces the main families of protein phosphatases encoded by the
      human genome and discusses their classification, overall structure, regulation,
      and physiological functions in human health and diseases. The topics of
      redundancy, diversity, and dynamic expression in individual cell types are
      briefly introduced, and the importance of technological approaches to phosphatase
      research is emphasized.

PMID- 17200552
TI  - Synthesis and use of the protein phosphatase affinity matrices microcystin
      sepharose and microcystin-biotin-sepharose.
AB  - Microcystin-based affinity matrices have been utilized to demonstrate the
      association of signaling proteins with protein phosphatases and for the
      purification of low-abundance microcystin-sensitive protein phosphatases. Here,
      we describe the procedure for the synthesis and use of microcystin-Sepharose and
      microcystin-biotin-Sepharose.

PMID- 17200551
TI  - Small-molecule inhibitors of ser/thr protein phosphatases: specificity, use and
      common forms of abuse.
AB  - Natural product extracts have proven to be a rich source of small molecules that
      potently inhibit the catalytic activity of certain PPP-family ser/thr protein
      phosphatases. To date, the list of inhibitors includes okadaic acid (produced by
      marine dinoflagelates, Prorocentrum sp. and Dinophysis sp.), calyculin A,
      dragmacidins (isolated from marine sponges), microcystins, nodularins
      (cyanobacteria, Microcystis sp. and Nodularia sp.), tautomycin, tautomycetin,
      cytostatins, phospholine, leustroducsins, phoslactomycins, fostriecin (soil
      bacteria, Streptomyces sp.), and cantharidin (blister beetles, approx 1500
      species). Many of these compounds share structural similarities, and several have
      become readily available for research purposes. Here we will review the
      specificity of available inhibitors and present methods for their use in studying
      sensitive phosphatases. Common mistakes in the employment of these compounds will
      also be addressed briefly, notably the widespread misconception that they only
      inhibit the activity of PP1 and PP2A. Inhibitors of PP2B (calcineurin) will only
      be mentioned in passing, except to state that, in our hands, cypermethrin,
      deltamethrin, and fenvalerate, which are sold as potent inhibitors of PP2B, do
      not inhibit the catalytic activity of PP2B.

PMID- 17200553
TI  - Utilizing protein phosphatase inhibitors to define PP2A as a regulator of ataxia
      telangiectasia mutated.
AB  - Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase that
      plays a central role in controlling the cellular response to DNA double-strand
      breaks caused by ionizing radiation. Ionizing radiation induces the
      autophosphorylation of ATM on serine 1981; however, the precise mechanisms that
      regulate ATM autophosphorylation are not fully understood. By treating cells with
      okadaic acid, a cell-permeable protein phosphatase inhibitor, together with
      assays to quantify the activity of particular protein phosphatases, we have
      demonstrated that the autophosphorylation of ATM on serine 1981 is regulated by a
      protein phosphatase 2A-like activity. Here, we describe the series of experiments
      that employed protein phosphatase inhibitors to establish that ATM was regulated
      by a type-2A protein phosphatase.

PMID- 17200555
TI  - An in vivo assay to quantify stable protein phosphatase 2A (PP2A) heterotrimeric
      species.
AB  - Protein phosphatase 2A (PP2A) regulates a broad spectrum of cellular processes.
      The enzyme is, in fact, largely a collection of varied heterotrimeric species
      composed of a catalytic (C) subunit and regulatory (B-type) subunit bound
      together by a structural (A) subunit. One important feature of the C subunit is
      that its carboxy-terminus can be modified by phosphorylation and methylation. The
      mechanisms that trigger such posttranslational modifications, as well as their
      consequences, are still under investigation. However, data collected thus far
      indicate that these modifications alter the binding to B subunits for an AC
      dimer, thereby affecting the makeup of the PP2A species in the cell. In this
      chapter, we describe an in vivo assay for assessing stable PP2A heterotrimer
      formation that is based on specific subcellular localizations of PP2A
      heterotrimers. This assay can be used to study the impact of a wide variety of
      alterations (such as mutations and covalent modifications) on PP2A heterotrimer
      formation. We specifically describe the use of this assay to quantify the effects
      of methylation on the stable formation of PP2ARts1p and PP2ACdc55p heterotrimers.

PMID- 17200554
TI  - An automated fluorescence-based method for continuous assay of PP2A activity.
AB  - Protein serine/threonine phosphatase (PP2A) is a major cellular enzyme implicated
      in the control of numerous signaling processes. The accurate measurement of PP2A
      activity in crude cell lysates, immune complexes, and purified preparations
      provides insight into the function and regulation of this essential enzyme,
      which, in turn, can lead to a better understanding of the signaling pathways that
      it modulates. The method presented here utilizes 6,8-difluoro-4
      methylumbelliferyl phosphate (DiFMUP) and a FLEXstation for the continuous
      measure of PP2A activity associated with many different protein preparations.
      This automated fluorescence-based assay offers several distinct advantages over
      colorimetric and radioactive assays of phosphatase activity including (1)
      decreased substrate preparation time, (2) real-time kinetic data, (3) high
      sensitivity, and (4) the capability to analyze a wide variety of phosphatases.

PMID- 17200556
TI  - Mutagenesis and expression of the scaffolding Aalpha and Abeta subunits of PP2A:
      assays for measuring defects in binding of cancer-related Aalpha and Abeta
      mutants to the regulatory B and catalytic C subunits.
AB  - Protein phosphatase 2A (PP2A) holoenzymes are composed of three subunits: one
      scaffolding A subunit, one regulatory B subunit, and one catalytic C subunit. The
      A subunit exists as two isoforms: Aalpha and Abeta. The C subunit also exists as
      two isoforms (Calpha and Cbeta) and B subunits fall into three families (B, B',
      and B") comprising over 15 members. The Aalpha and Abeta subunits consist of 15
      nonidentical repeats, which are composed of two amphipathic alpha helices that
      are connected by a loop (intrarepeat loop). These loops are instrumental in
      binding regulatory B and catalytic C subunits. The genes encoding the Aalpha and
      Abeta subunits are relatively frequent targets for mutation in human cancer. The
      mutations often affect the intrarepeat loops and cause defects in the binding of
      specific B subunits or of B and C subunits. Here, we describe in vitro and in
      vivo binding assays for measuring these defects. Knowing which B subunits are
      affected in binding to the mutant A subunits sheds light on which holoenzymes
      might be involved in growth control and cancer.

PMID- 17200557
TI  - Isolation and characterization of PP2A holoenzymes containing FLAG-tagged B
      subunits.
AB  - Protein serine/threonine phosphatase 2A (PP2A) is a major cellular enzyme
      implicated in the control of a wide variety of biological processes. The
      predominant form of PP2A in cells is a heterotrimeric holoenzyme (ABC) consisting
      of a scaffolding (A) subunit, a regulatory (B) subunit, and a catalytic (C)
      subunit. Although numerous signal transduction pathways are known to be regulated
      by PP2A, the identity of the PP2A holoenzymes controlling each pathway remains
      unclear. Studies aimed at elucidating substrates for individual PP2A holoenzymes
      have been hindered by the limited availability of purified endogenous holoenzymes
      and the inability to differentiate cellular roles of closely related PP2A
      holoenzymes. In this chapter, we describe a strategy for the functional
      expression of select FLAG-tagged regulatory B subunits in human embryonic kidney
      293 cells and subsequent purification of PP2A holoenzymes containing the FLAG
      tagged B subunit and endogenous A and C subunits (ABFLAGC). Biochemical analyses
      of the purified ABFLAGC holoenzymes reveal that they exhibit virtually
      indistinguishable specific activities and sensitivities to inhibitors as compared
      to the corresponding endogenous PP2A holoenzymes. The strategy described herein
      provides a straightforward method to purify individual PP2A holoenzymes from
      target mammalian cells for subsequent in vitro studies, as well as a powerful
      approach to identify cellular substrates and roles for each holoenzyme.

PMID- 17200558
TI  - Purification of PP2A holoenzymes by sequential immunoprecipitation with anti
      peptide antibodies.
AB  - Understanding the multiple functions of protein phosphatase 2A (PP2A) rests on
      elucidating the enzymatic properties of over 50 different possible forms of the
      PP2A holoenzyme. We describe a procedure for highly purifying each one of these
      forms. This procedure is based on coexpressing in 293 cells one scaffolding A
      subunit, one regulatory B subunit, and one catalytic C subunit, each tagged with
      a different sequence, and purifying the trimeric holoenzyme by three consecutive
      immunoprecipitations with antibodies against the tags. In a few hours and from a
      small number of cells, sufficient enzyme can be purified for enzymatic studies.
      Purification of six different holoenzymes in parallel can easily be accomplished.

PMID- 17200559
TI  - Purification of PP2Ac from bovine heart.
AB  - The catalytic subunit of PP2A (PP2Ac) can be purified in milligram quantities
      from bovine heart using ethanol precipitation, ammonium sulfate precipitation,
      ion exchange and size exclusion chromatography. The detailed procedure is
      described to purify PP2Ac over 4 d.

PMID- 17200560
TI  - Visualization of intracellular PP1 targeting through transiently and stably
      expressed fluorescent protein fusions.
AB  - Protein phosphatase 1 (PP1) is a ubiquitous serine/threonine phosphatase that
      regulates many cellular processes, including cell division, signaling,
      differentiation, and metabolism. It is expressed in mammalian cells as three
      closely related isoforms: alpha, beta/delta, and gamma1. These isoforms differ in
      their relative affinities for proteins, termed targeting subunits, that mediate
      their intracellular localization and substrate specificity. Because of the
      dynamic nature of these interactions, it is important to find experimental
      approaches that permit direct analyses of PP1 localization and PP1-targeting
      subunit interactions in live cells. When transiently or stably expressed as
      fluorescent protein (FP) fusions, the three isoforms are active phosphatases with
      distinct localization patterns and can interact with both endogenous and
      exogenous targeting subunits. Their changing spatio-temporal distributions can be
      monitored both throughout the cell cycle and following cellular perturbations by
      time-lapse fluorescence microscopy, and turnover rates of intracellular pools of
      the protein calculated by fluorescence recovery after photobleaching (FRAP).
      Interactions with targeting subunits can be visualized in vivo by fluorescence
      resonance energy transfer (FRET), using techniques such as sensitized emission,
      acceptor photobleaching, or fluorescence lifetime imaging.

PMID- 17200561
TI  - Yeast two-hybrid screens to identify Drosophila PP1-binding proteins.
AB  - Protein phosphatase type 1 (PP1) is one of the major classes of serine/threonine
      protein phosphatases and has been found in all eukaryotic cells examined to date.
      Metazoans from Drosophila to humans have multiple genes encoding catalytic
      subunits of PP1 (PP1c), which are involved in a wide range of biological
      processes. Studies in the fruit fly Drosophila melanogaster have revealed some of
      the essential functions of the PP1c genes. However, the PP1c isoforms have
      pleiotropic and overlapping functions, making it difficult to characterize their
      many biological roles and identify their specific in vivo substrates. Regulatory
      subunits of PP1 provide the key to understanding the role of PP1, as they are
      responsible for directing PP1c to different intracellular locations and/or
      affecting their activity or substrate specificity. The existence of isoform
      specific PP1 regulatory subunits might also help to explain the unique roles of
      different PP1 catalytic subunits. Drosophila is an excellent model organism in
      which to characterize the role of PP1 catalytic and regulatory subunits, because
      it combines molecular and biochemical approaches with powerful genetics, in a
      well-characterized animal model. In this chapter, we will describe how the two
      hybrid system can be used to identify Drosophila PP1c-interacting proteins and
      study their interactions with different PP1c isoforms and variants. With the
      appropriate bait and library constructs, this method should also be equally
      applicable to identifying binding subunits of related phosphatases or PP1c from
      other organisms.

PMID- 17200562
TI  - Identification of cellular protein phosphatase-1 regulators.
AB  - Protein phosphatase-1 (PP1) is a major phosphoserine/phosphothreonine phosphatase
      that regulates multiple physiological events in all eukaryotic cells. Action of
      PP1 in cells is dictated by the association of PP1 catalytic subunit with one or
      more regulatory subunits that define both its catalytic function and subcellular
      localization. This chapter describes key methods used to identify PP1-binding
      proteins and assess their ability to modulate PP1 functions in mammalian cells.
      These methods include affinity isolation of cellular PP1 complexes, analysis of
      direct PP1 binding, modulation of PP (protein phosphatase) activity, and testing
      for the presence of the newly identified PP1 complex in cells and cellular
      compartments. Together these techniques set the foundation for further studies
      that can establish the physiological significance of this PP1 complex.

PMID- 17200563
TI  - Assay for three-way interaction of protein phosphatase-1 (Glc7) with regulatory
      subunits plus phosphatase inhibitor-2.
AB  - A method is described using yeast conjugation to assay the interactions of a
      protein phosphatase-1 (PP1) inhibitor protein with holoenzymes formed in situ by
      expression of regulatory subunit fusion proteins that recruit endogenous Glc7,
      the yeast ortholog of PP1. Mutations in the canonical recognition motif VxF used
      to bind PP1 (Glc7) allow for analysis of direct from indirect (three-way)
      interactions.

PMID- 17200565
TI  - Purification of smooth muscle myosin phosphatase using a thiophosphorylated
      myosin light-chain-affinity resin.
AB  - Many protein kinases are able to catalyze the thiophosphorylation of protein
      substrates via a phospho-transfer reaction using adenosine-5'-o(3
      thiotriphosphate) (ATPgammaS) (1), but, in general, thiophosphorylated proteins
      are very poor substrates for protein phosphatases (2,3). As a result, the protein
      substrate is essentially trapped in the phosphorylated state. This
      thiophosphorylation can be exploited in order to generate a strategy for the
      selective purification of protein phosphatases. Indeed, a number of
      thiophosphorylated protein substrates have been successfully used for the
      affinity purification of protein phosphatases (4-7). Here we describe the use of
      thiophosphorylated smooth muscle myosin regulatory light chains for the selective
      purification of the smooth muscle myosin phosphatase holoenzyme.

PMID- 17200564
TI  - Phosphorylation of the protein phosphatase type 1 inhibitor protein CPI-17 by
      protein kinase C.
AB  - CPI-17 is a cytosolic protein of 17 kDa that becomes a potent inhibitor of
      certain type 1 protein serine/threonine phosphatases, including smooth muscle
      myosin light-chain phosphatase (MLCP), when phosphorylated at Thr38. Several
      protein kinases are capable of phosphorylating CPI-17 at this site in vitro;
      however, in intact tissue, compelling evidence only exists for phosphorylation by
      protein kinase C (PKC). Agonist-induced activation of heterotrimeric G proteins
      of the Gq/11 family via seven-transmembrane domain-containing, G protein-coupled
      receptors results in phospholipase Cbeta-mediated hydrolysis of membrane
      phosphatidylinositol 4,5-bisphosphate to generate inositol 1,4,5-trisphosphate
      (IP3) and 1,2-diacylglycerol (DAG). IP3 triggers Ca2+ release from the
      sarcoplasmic reticulum. DAG and Ca2+ together activate classical isoforms of PKC,
      and DAG activates novel PKC isoforms without a requirement for Ca2+. Activated
      PKC phosphorylates CPI-17 at Thr38, enhancing its potency of inhibition of MLCP
      approx 1000-fold. The myosin light-chain kinase (MLCK):MLCP activity ratio is
      thereby increased at the prevailing cytosolic free-Ca2+ concentration ([Ca2+]i),
      resulting in an increase in phosphorylation of the 20-kDa light chains of myosin
      II (LC20) catalyzed by Ca2+- and calmodulin-dependent MLCK and contraction of the
      smooth muscle. Physiologically, this mechanism can account for some instances of
      Ca2+ sensitization of smooth muscle contraction (i.e., an increase in force in
      response to agonist stimulation without a change in [Ca2+]i).

PMID- 17200566
TI  - Proteins interacting with Saccharomyces cerevisiae type 1 protein phosphatase
      catalytic subunit identified by single-step affinity purification and mass
      spectrometry.
AB  - The catalytic subunit of type 1 protein phosphatase (PP1C) interacts with a large
      number of polypeptides in eukaryotic cells from yeast to man and these regulatory
      subunits can both modulate the activity of PP1C and target it to different
      subcellular locations. Thus, PP1 is really a family of protein phosphatases that
      share a common catalytic subunit, and identifying and characterizing the PP1
      associated proteins is therefore critical to understanding the cellular roles of
      PP1 and its ability to dephosphorylate specific substrates. Here we describe
      methods for affinity isolation of PP1C-containing protein complexes in the yeast
      Saccharomyces cerevisiae and the identification of the associated polypeptides by
      mass spectrometry. The basic method we describe could be easily adapted to study
      PP1C-associated proteins in other lower or higher eukaryotes and for
      characterizing the protein-protein interactions of other protein phosphatases in
      yeast.

PMID- 17200567
TI  - Expression of protein histidine phosphatase in Escherichia coli, purification,
      and determination of enzyme activity.
AB  - A protein histidine phosphatase (PHP) from vertebrates was first identified in
      2002. Here we describe the expression of that PHP in Escherichia coli and
      purification of the recombinant protein. In addition, a detailed protocol is
      provided describing determination of PHP activity in vitro. Proteins
      phosphorylated on histidine residues in general cannot be easily obtained. This
      also applies to the substrates of PHP. To circumvent that obstacle, assay
      conditions are introduced enabling scientists to study PHP activity using a
      substrate within crude homogenates of cells and tissues.

PMID- 17200568
TI  - The use of RNA interference to analyze protein phosphatase function in mammalian
      cells.
AB  - The use of RNA interference to knock down protein phosphatases has proven to be a
      valuable approach to understanding the functions of these enzymes in mammalian
      cells. Many protein phosphatases exist as multisubunit and multigene families,
      which has made it difficult to assess their physiological functions using
      traditional approaches. The ability to selectively knock down specific subunits
      and individual isoforms with RNA interference has begun to make it possible to
      determine the contributions of individual phosphatase proteins to cellular
      signaling. This chapter describes methods for knocking down protein phosphatases
      with small interfering RNAs in easily transfectable cells and by the introduction
      of short-hairpin RNAs into less tractable cells using lentivirus vectors.

PMID- 17200569
TI  - Recognition of a PP2C interaction motif in several plant protein kinases.
AB  - Protein phosphatase 2Cs (PP2Cs) constitute a major class of phosphatases in
      plants. PP2Cs play important roles in many signaling pathways by countering the
      action of specific protein kinases. In addition to their role in several
      environmental stress-related signal transduction pathways, they are also involved
      in plant metabolism. Protein phosphatases often physically associate with their
      protein kinase counterparts. One approach to understanding PP2C function is to
      identify their interacting protein kinases. We describe a yeast two-hybrid assay
      system used in our lab to determine the interaction between members of the PP2C
      family and protein kinases in the SOS2 family. This chapter and the cited
      articles describing related work might be of help in discovering interactions
      between other protein phosphatases and kinases.

PMID- 17200570
TI  - Use of yeast genetic tools to define biological roles of novel protein
      phosphatases.
AB  - Regulatable gene expression is a powerful genetic tool for analyzing the function
      of a given gene product. The use of tetracycline-regulatable promoters in yeast
      represents a substantial improvement over previously described methods for gene
      regulation. Here we show how this approach can be used to analyze the biological
      role of serine/threonine phosphatase catalytic or putative regulatory subunits by
      constructing chromosomal or plasmid-borne conditional mutants. This is
      particularly useful given the large variety of important biological processes
      performed by these of enzymes, often necessaries for cell survival, which makes
      in some cases infeasible the generation of null mutants.

PMID- 17200571
TI  - Targeting of PP2C in budding yeast.
AB  - Type 2C Ser/Thr phosphatases or PP2Cs are monomeric metal-requiring protein
      phosphatases that are present in prokaryotes and eukaryotes. In the yeast
      Saccharomyces cerevisiae, there are seven PP2Cs called PTCs (phosphatase 2C).
      Molecular genetic studies have implicated PTCs in many different functions,
      including RNA splicing, the unfolded protein response, mitogen-activated protein
      kinase (MAPK) pathway, and cell-cycle regulation. We have shown that three PTCs
      (Ptc1, Ptc2, and Ptc3), regulate the stress-activated high-osmolarity glycerol
      (HOG) mitogen-activated protein kinase (MAPK) pathway. Proteomics studies have
      provided additional possible functions for these phosphatases by identifying
      interacting proteins. These studies have also provided the possible means by
      which these phosphatases are targeted to their substrates. For example, Nbp2-Ptc1
      was identified as an interacting pair in yeast two-hybrid studies, and Nbp2 was
      found together with Ptc1 and HOG pathway kinases. We have shown that Nbp2 is an
      adapter in this pathway, mediating interaction between Ptc1 and the Pbs2 MAP/ERK
      kinase in the HOG pathway.

PMID- 17200572
TI  - Phosphatase targets in TOR signaling.
AB  - Cells undergo growth or increase in mass in the presence of nutrients. A key
      signaling molecule that responds to the presence of nutrients is the target of
      rapamycin (TOR). TOR is a highly conserved protein kinase and is the target of
      the growth inhibitor rapamycin. In response to nutrients, TOR promotes the
      phosphorylation of its downstream targets, leading to increased protein synthesis
      and decreased protein turnover. In yeast, a major mechanism for the downstream
      regulation of TOR effectors is by inhibition of the type 2A-related phosphatase
      SIT4. TOR negatively regulates SIT4 by promoting the association of SIT4 with
      TAP42. When TOR is inactivated by rapamycin treatment or nitrogen starvation,
      downstream effectors of TOR such as the serine/threonine protein kinase NPR1 and
      the TAP42 interacting protein TIP41 are dephosphorylated in a SIT4-dependent
      manner. The phosphorylation state of NPR1 and TIP41 provides a convenient readout
      in yeast to assay for TOR and SIT4 activities under growth-promoting or growth
      inhibitory conditions.

PMID- 17200573
TI  - Functional characterization of small CTD phosphatases.
AB  - The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase
      (RNAP) II undergoes reversible phosphorylation with each round of transcription
      essential for the regulation of gene expression. A family of small CTD
      phosphatases (SCPs) was identified based on a homology search to TFIIF
      associating CTD phosphatase 1 (FCP1). Unlike FCP1, SCP preferentially catalyze
      the dephosphorylation of Ser5 within the CTD and is especially active toward RNAP
      II phosphorylated by TFIIH (1). Recently, SCP1 was demonstrated as a
      transcriptional regulator that acts to silence neuronal genes (2). This chapter
      describes the procedures for various assays involved in the discovery and
      functional characterization of SCPs.

PMID- 17200574
TI  - Genome-scale discovery and characterization of class-specific protein sequences:
      an example using the protein phosphatases of Arabidopsis thaliana.
AB  - The increasing pace of acquisition of fully sequenced genomes makes desirable a
      program of discovery and characterization of protein sequences of biologically
      significant structural classes. An example is protein phosphatases, involved in
      modulating reversible protein phosphorylation events underlying the whole gamut
      of cellular biology. The ready availability of software that can be downloaded to
      run on a personal computer, or accessed on a server via the Web, allows
      appropriate sequences to be collected and analyzed. A process is outlined here
      that has been successfully employed in the description of the genomic complement
      of protein phosphatase catalytic subunits from the model plant Arabidopsis
      thaliana. However, the methods are general and readily adapted to deal with any
      desired class of protein, from any organism of interest.

PMID- 17200575
TI  - Yeast substrate-trapping system for isolating substrates of protein tyrosine
      phosphatases.
AB  - Protein tyrosine phosphorylation, controlled by the activities of both protein
      tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), plays critical
      roles in a wide variety of cellular events. However, in contrast to the PTKs, our
      understanding of the biological functions of PTPs has been limited to date. This
      is mainly the result of the difficulty in identifying the substrate molecules of
      individual PTPs. We described a genetic method to screen for PTP substrates,
      which we have named the "yeast substrate-trapping system." This method is based
      on the yeast two-hybrid system with two essential modifications: the conditional
      expression of a PTK to tyrosine-phosphorylate the prey protein, and screening
      using a substrate-trap PTP mutant as bait. This system is conceptually applicable
      to all the PTPs, because it is based on PTP-substrate interaction in vivo, namely
      the substrate recognition of individual PTPs. The identification of physiological
      substrates will shed light on the physiological functions of individual PTPs.

PMID- 17200577
TI  - Rocky mountain spotted fever.

PMID- 17200578
TI  - Six days in Charity Hospital: two doctors' ordeal in Hurricane Katrina.
AB  - Hurricane Katrina devastated the city of New Orleans as well as a large section
      of the Gulf Coastal region of the United States. Herein, we present a first-hand
      view of physicians who were actually running the hospital of a major medical
      center during this natural disaster. This event demonstrates the vulnerability of
      basic human services, including health care even in industrialized, wealthy
      countries.

PMID- 17200579
TI  - Ablation pit treatment for corneal decompensation.
AB  - Historically, the management of cloudy, decompensated corneas centered around
      replacement of corneal tissue with either a through-and-through or partial
      thickness replacement. This article presents a technique that is a radical
      departure from prior methods.

PMID- 17200580
TI  - Combined trabeculotomy-trabeculectomy as a first surgical procedure for primary
      congenital glaucoma.
AB  - Early surgical results (mean follow-up = 163 days) following combined
      trabeculotomy-trabeculectomy as a first surgical procedure for 20 consecutive
      cases in 14 children with primary congenital glaucoma were retrospectively
      examined. Mean pretreatment intraocular pressure was 25.55 +/- 9.58 mmHg,
      decreasing to 14.55 +/- 6.15 mmHg following treatment. Primary combined
      trabeculotomy-trabeculectomy was a useful initial procedure to control
      intraocular pressure in primary congenital glaucoma.

PMID- 17200581
TI  - Comparison of the inferior oblique weakening by disinsertion or disinsertion
      resection and tucking in the patient with infantile esotropia.
AB  - The effectiveness of disinsertion vs disinsertion-resection and tucking procedure
      of the inferior oblique muscle for infantile esotropia was studied. Preoperative
      muscle overaction scores were +3.2 +/- 0.6 and +3.3 +/- 0.48 for the two groups,
      respectively. Postoperatively, there was + 0.52 average score in five Group I
      cases, whereas there were none in Group 2. We conclude that the disinsertion
      resection and tucking procedure is more effective than simple disinsertion.

PMID- 17200582
TI  - The red eye.
AB  - A red eye is a cardinal sign of ocular inflammation. Most cases are benign and
      can be managed by the primary care provider. The key is recognizing cases
      requiring ophthalmological consultation by differentiating between ciliary and
      conjunctival injection. Ciliary injection indicates inflammation of the cornea,
      iris, or ciliary body, whereas conjunctival injection mainly affects the
      posterior conjunctival blood vessels.

PMID- 17200583
TI  - Are high-water-content contact lenses safe?
AB  - We examined the role of tear secretion on contact lens water content during
      selection. Tear secretion was estimated using Schirmer's tests. High-water
      content contact lenses compromised the tear film more than low-water-content
      contact lenses, hence they should not be advised in low or marginal Schirmer's
      test cases.

PMID- 17200584
TI  - The histopathological effect of intracameral ropivacaine in different
      concentrations on corneal endothelium.
AB  - We evaluated the histopathological changes occurring in corneal endothelium after
      intracameral injection ropivacaine into rats. Intracamerally administered
      ropivacaine in 1, 0.5, and 0.1% concentrations resulted in impairment of
      hexagonal structure of corneal endothelial cells and intercellular junctions,
      destruction of microvilli on the cell surface, roughness of cell borders,
      picnotic nucleus, diffuse vacuolization, and crystalysis in mitochondria.

PMID- 17200585
TI  - Ophthalmic chapters of Serefeddin Sabuncuoglu's illustrated surgical book
      (Cerrahiyyetu'l Haniyye) in the 15th century.
AB  - Serefeddin Sabuncuoglu wrote Cerrahiyyetu'l Haniyye (Imperial Surgery) in 1465.
      It was the first illustrated surgical textbook in the Turkish-Islamic medical
      literature. Only three handwritten copies exist. Cerrahiyyetu'l Haniyye consists
      of three chapters (412 pp.) covering a wide range of surgical specialties,
      including medical and surgical management of such ophthalmic diseases as
      chalazion, symblepharon, lymphangiectasia, pannus, proptosis, and hypopyon.

PMID- 17200586
TI  - Functional health status of patients at initial visit in primary eye clinic
      assessed using the Japanese versions of the COOP charts.
AB  - Patient health status was evaluated using Japanese versions of COOP charts. The
      subconjunctival hemorrhage group scored 3.6 in overall health and 3.7 in change
      in health. The painful outer eye disease group scored higher than 3.0 in feeling,
      pain, change in health, and quality of life. The seeing floaters group scored
      higher than 3.0 in feeling, overall health, change in health, and quality of
      life.

PMID- 17200587
TI  - Comparison of corneal edema caused by cataract surgery with different phaco times
      in diabetic and non-diabetic patients.
AB  - Corneal thickness changes caused by phacoemulsification times were compared in
      diabetic and non-diabetic patients. Corneal thicknesses were greater in the first
      postoperative week both in diabetic and non-diabetic patients than in later
      follow-up. Later corneal thicknesses were not different according to phacotimes
      or diabetic status. In terms of corneal thickness changes, uncomplicated
      phacoemulsification is safe in diabetics and non-diabetics.

PMID- 17200588
TI  - Triamcinolone pseudo-cataract.
AB  - This is an interventional case report of a pseudo-cataract formation by the
      adherence of triamcinolone particles to the posterior surface of the lens
      following a 2-mg intravitreal injection for treatment of macular edema associated
      with non-ischemic central retinal vein occlusion. These deposits unusually
      persisted beyond 6 months.

PMID- 17200590
TI  - Histopathological study of a case with branch retinal vein occlusion.
AB  - A retinal specimen from a 68-year-old patient with glaucoma and branch retinal
      vein occlusion was examined by light and electron microscopy. The venous and
      arterial lumina were filled with erythrocytes, and many erythrocytes extravasated
      into the venous wall. We suggest that constant rubbing of endothelial cells of
      the occluded vein results in damage and erythrocyte extravasation was caused by
      diapedesis.

PMID- 17200589
TI  - Metastatic tumor of orbit presenting as pulsatile proptosis.
AB  - Pulsatile proptosis is caused by vascular lesion of orbit or by herniation of
      brain through bony defect in orbit. Pulsatile proptosis secondary to a metastatic
      tumor of orbit is very uncommon. We report a 69-year-old male who presented with
      pulsatile proptosis owing to metastasis of an asymptomatic renal cell carcinoma.

PMID- 17200591
TI  - Bee sting of the cornea: a case study and review of the literature.
AB  - Bee stings of the cornea are rarely reported, but have the potential for causing
      serious ophthalmological injuries. We present a case of corneal bee sting with
      retained stinger apparatus. A 35-year-old patient presented with an acute,
      corneal bee sting of the right eye 12 hours after he was stung. The patient
      suffered from pain, blurred vision, and epiphora. The right eye showed edema of
      the upper and lower eyelid, conjunctival hyperemia, chemosis, and striate
      keratitis of the paracentral cornea by biomicroscopic examination. The stinger
      was identified in the depth of the corneal infiltration. Visual acuity was 5/10.
      It was removed surgically. After 2 months, the eye only showed a minimal residual
      corneal opacification. Visual acuity was 10/10. We present a case of bee sting to
      the cornea with retained stinger apparatus and treatment of this unusual
      presentation.

PMID- 17200592
TI  - Bilateral -14.0 diopters index myopia successfully treated with cataract surgery:
      a case report.
AB  - We report a 60-year-old man with bilateral nuclear cataract and -14.0 diopters
      index myopia. Following uncomplicated phacoemulsifications and posterior chamber
      intraocular lens implantations on both eyes, right and left axial lengths were
      22.58 and 22.60 mm with otobiomeric A-scan ultrasound, respectively. Three-month
      corrected visual acuity was 20/20 in the right eye with a -1.00 x 130 degrees
      cylinder and 20/20 in the left eye with -0.50 spheres and -1.00 x 100 degrees
      cylinders.

PMID- 17200594
TI  - The cost of schizophrenia: lessons from an international comparison.
AB  - BACKGROUND: A number of studies have attempted to estimate the aggregate burden
      of mental illness in particular countries. It has been observed that the economic
      costs vary by country. This is particularly true for estimates of the cost of
      schizophrenia, a severe mental illness that can lead to major psychiatric
      disability. The reasons for this may be due to differences in populations,
      measurement methods or quality of care. AIMS OF THE STUDY: This paper reviews
      three key studies of the cost of schizophrenia in Canada, the United States and
      the United Kingdom with an emphasis on a US-Canada comparison. The detailed focus
      allows for an in-depth study of the factors that lead to different cost
      estimates. A secondary aim of this paper is to illustrate the importance of
      direct and indirect costs in the measurement of economic burden. METHODS: We
      explore various hypotheses about why three major studies of the economic burden
      of schizophrenia suggest large differences in the estimated per capita costs when
      expressed in the same currency. We discuss adjustments that may be made in the
      reported cost estimates to account for factors such as higher wages or lower
      administrative costs, in order to make them more comparable. RESULTS: In spite of
      the many adjustments, the estimated per capita resources spent on care for people
      with schizophrenia in Canada is less than half of the corresponding amount in the
      US (1,122 million dollars compared to 2,306 million dollars). Even though
      adjusting for per capita income narrows the apparent gap between the Canadian and
      US figures, it still remains very large. Since adjusting for per capita income
      almost certainly over-adjusts for resources spent in the US as compared to
      Canada, it is clear that the true difference is very large. Even though the per
      capita direct costs in Canada are only about a third as large as the
      corresponding US figure, the UK figure is less than half of Canada's.
      Coincidentally, if one assumes that the true prevalence rate in the UK is similar
      to that estimated for Canada and adjusts figures accordingly, the result is an
      estimate for direct costs that is quite similar to the Canadian one. DISCUSSION
      AND LIMITATIONS: With respect to direct costs, a key finding in the paper is the
      very large difference in the per capita cost of treatment of schizophrenia in
      Canada and the United States. From the standpoint of Canadian public policy, the
      worrisome policy question that this raises is whether the findings reflect, on
      average, a relatively less satisfactory level of treatment for those with
      schizophrenia in Canada. An important limitation is that we do not analyze
      quality of care data. Our detailed item by item comparison of the estimates
      attempts to rule out alternative explanations in order to discover whether a
      quality difference may actually exist. IMPLICATIONS FOR HEALTH POLICIES: This
      research reviews US and international estimates of the economic burden of
      schizophrenia. In the process of summarizing what is known, a remarkable
      difference in the direct cost of schizophrenia is uncovered. Possible
      methodological and economic explanations are investigated (e.g., adjustments for
      different financial currencies and study methodologies). Nevertheless, the
      results appear robust to a variety of sensitivity analyses. From the standpoint
      of public policy, the worrisome question that this raises is whether these
      findings reflect, on average, a relatively lower quality of care for Canadians
      with schizophrenia or wasteful care for Americans with schizophrenia.

PMID- 17200595
TI  - Convergence of service, policy, and science toward consumer-driven mental health
      care.
AB  - BACKGROUND: A common theme is emerging in sentinel reports on the United States
      health care system. Consumer relevance and demands on service systems and
      practices are influencing how mental health care is delivered and how systems
      will be shaped in the future. AIMS OF THE STUDY: The present report seeks to
      assemble a confluence of consumer-driven themes from noteworthy reports on the
      state of the mental health system in the U.S. It also explores innovative
      efforts, promising practices, collaborative efforts, as well as identification of
      barriers to consumer-directed care, with possible solutions. METHOD: The report
      reviews the relevant public mental health policy and data used in published work.
      RESULTS: The findings indicate an increasing public and private interest in
      promoting consumer-driven care, even though historical systems of care
      predominate, and often create, barriers to wide-spread redesign of a consumer
      centered mental health care system. Innovative consumer-driven practices are
      increasing as quality, choice, and self-determination become integral parts of a
      redesigned U.S. mental health care system. DISCUSSION AND LIMITATIONS: The use of
      consumer-driven approaches in mental health is limited at best. These programs
      challenge industry norms and traditional practices. Limitations include the need
      for additional and thorough evaluations of effectiveness (cost and clinical) and
      replicability of consumer-directed programs. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: Consumer-driven services indicate that mental health consumers
      are expecting to be more participative in their mental health care. This
      expectation will influence how traditional mental health services and providers
      become more consumer-centric and meet the demand. IMPLICATIONS FOR HEALTH
      POLICIES: Public and private interest in consumer-driven health care range from
      creating cost-conscious consumers to individualized control of recovery. The
      health care sector should seek to invest more resources in the provision of
      consumer-driven health care programs. The results of this study have implications
      and are informative for other countries where consumer-directed care is delivered
      in either the private or public health care systems. IMPLICATIONS FOR FURTHER
      RESEARCH: More research is needed to obtain further evidence on the use of
      consumer-driven services and their overall effectiveness.

PMID- 17200596
TI  - Costs of nine common mental disorders: implications for curative and preventive
      psychiatry.
AB  - BACKGROUND: Mental disorders are highly prevalent and are associated with
      substantial disease burden, but their economic costs have been relatively less
      well researched. Moreover, few cost-of-illness studies used population-based
      psychiatric surveys for estimating direct medical, direct non-medical and
      indirect costs, and were able to do so for several well diagnosed mental
      disorders. AIMS: To calculate the cost of nine common mental disorders. The costs
      were calculated at individual level (per capita costs), and at population level
      per one million population for both prevalence (current cases) and incidence (new
      cases). METHOD: Data were derived from the Netherlands Mental Health Survey and
      Incidence Study (Nemesis), a population-based psychiatric cohort study among
      5,504 adults in the age bracket of 18-65 years. DSM-III-R disorders were assessed
      with help of the Composite International Diagnostic Interview (CIDI). The costs
      of health service uptake, patients' out-of-pocket costs, and production losses
      were calculated for the reference year 2003. Robust regression methods, with
      1,000 bootstrap replications, were used to estimate the excess costs of the
      distinct mental disorders and their 95% confidence intervals, while adjusting for
      physical illnesses and concurrent mental disorders in the regression equation.
      RESULTS: The annual per capita excess costs of the mood disorders (5,009 euros)
      were higher than those of the anxiety disorders (3,587 euros) and alcohol-related
      disorders (1,431 euros). Being more prevalent, the excess costs of anxiety
      disorders are higher than those of mood disorders at population level. The annual
      influx of new cases (incidence) accounts for 39.2% of the costs at population
      level. It appeared that in the general population, in the productive age of 18-65
      years, the bulk of the costs (85%) were related to production losses. DISCUSSION:
      The study has some strengths and limitations. The data were derived from a large
      and representative population-based sample. Disorders were assessed with a
      reliable instrument. The costs were comprehensive in that they included direct
      medical, direct non-medical and indirect costs. The costs attributable to mental
      disorders were obtained with robust regression models while adjusting for the
      presence of somatic illnesses. For several reasons the costs figures must be seen
      as conservative lower bounds of the true costs. (i) People who were hospitalised
      were likely to be underrepresented in the sample, and it is well known that
      hospitalisation is one of the major cost drivers. (ii) Resource use was based on
      self-report, and this is likely to have resulted in underreporting. (iii) Work
      loss days were included in the analysis, but work cutback data were unavailable,
      while it is known that the costs due to work cutback can be substantial.
      IMPLICATIONS: (i) The costs of mental disorders are comparable to those of
      physical illnesses. This throws some light on the allocation of budgets for
      research and development in mental versus physical illnesses. (ii) At population
      level a substantial part of the costs are caused by new cases, and this is a
      strong argument for strengthening the role of preventive psychiatry in public
      health with the aim to reduce incidence and avoid the future costs. (iii) In
      particular, reducing the incidence of major depression, panic disorder,
      agoraphobia and dysthymia should be considered as public health priorities,
      because these disorders are associated with substantial disability, and have, in
      addition, important economic ramifications. (iv) The bulk of the costs are due to
      production losses; this makes employers pertinent stakeholders in mental health
      promotion, and thoughts should be given to the question how to involve them more
      actively in health promotion. (v) It is well to emphasise that adoption of the
      above mentioned policies will require that first more prevention trials and cost
      effectiveness studies are conducted in the selected disorders.

PMID- 17200597
TI  - Health care resource use associated with integrated psychological treatment.
AB  - BACKGROUND: Mental health policies, advocating outpatient as well as community
      mental health care for the severely mentally ill, are aiming towards health
      system cost containment and patient quality of life. Programs with cognitive
      behavioral therapy, such as the Integrated Psychological Therapy (IPT), added to
      standard medical therapy for patients with schizophrenia have been associated
      with improved outcomes. A Quebec version of the IPT program was integrated in
      outpatient clinics and improvements were observed in overall symptoms, subjective
      experiences, cognitive and social functioning, and quality of life. In light of
      these results we deemed it relevant to describe the health system cost and
      patient resource use associated with the program. The costs related to IPT have
      not been previously reported and this study will elucidate on effective health
      services and budget allocation needed to include IPT. AIMS: To describe health
      care resource use and related costs associated with participating in an IPT
      program included as standard medical therapy in nine clinical settings. METHODS:
      A cohort of patients with schizophrenia participating in the IPT program were
      followed up to one year preceding the start of the program and concurrently until
      the end to compare the resource use and costs incurred by patients with
      schizophrenia during their participation. A health and social service system and
      patient perspective was adopted, and the medical and non-medical costs associated
      with the IPT program were measured. Valuation (2001 CDN dollars) was based on
      information provided by provincial billing systems. Statistical differences were
      assessed using the Wilcoxon signed-rank test. RESULTS: The IPT program induced a
      one time fixed cost (2347 dollars) for the training of mental health
      professionals and costs related to patient participation (1350 dollars). Our
      results show that there was an average decrease in health care system resource
      use per patient during the IPT program (26,133 dollars) as opposed to the
      preceding year (26,750 dollars). There was a significant decrease in the number
      of visits and in physician fees paid out to psychiatrists, the number of
      hospitalizations and related costs, and visits to the emergency department per
      patient during the IPT program as compared to the preceding year. No significant
      difference was observed in patient related costs which averaged 7295 dollars and
      7537 dollars, before and during the IPT program, respectively. DISCUSSION:
      Although the IPT program induces a one time fixed cost for training, the
      integration of IPT, as part of an individualized standard medical therapy, is
      associated with a change from inpatient towards outpatient resource use with no
      significant increase in health system related costs. IMPLICATIONS FOR HEALTH CARE
      PROVISION AND USE: Given clinical and quality of life improvements, the findings
      suggest that offering IPT to more patients with severe mental illness may prove
      more cost beneficial by decreasing the health system related costs per user in
      the long term. IMPLICATIONS FOR FURTHER RESEARCH: Additional research is needed
      to examine in parallel the long-term clinical and cost impact of the IPT program
      in different clinical settings (young adults to long term mentally ill). This
      will elucidate to which patient population IPT is most cost-effective.

PMID- 17200598
TI  - DNA-protein interactions and bacterial chromosome architecture.
AB  - Bacteria, like eukaryotic organisms, must compact the DNA molecule comprising
      their genome and form a functional chromosome. Yet, bacteria do it differently. A
      number of factors contribute to genome compaction and organization in bacteria,
      including entropic effects, supercoiling and DNA-protein interactions. A gamut of
      new experimental techniques have allowed new advances in the investigation of
      these factors, and spurred much interest in the dynamic response of the
      chromosome to environmental cues, segregation, and architecture, during both
      exponential and stationary phases. We review these recent developments with
      emphasis on the multifaceted roles that DNA-protein interactions play.

PMID- 17200599
TI  - Nanopore-facilitated, voltage-driven phosphatidylserine translocation in lipid
      bilayers--in cells and in silico.
AB  - Nanosecond, megavolt-per-meter pulses--higher power but lower total energy than
      the electroporative pulses used to introduce normally excluded material into
      biological cells--produce large intracellular electric fields without
      destructively charging the plasma membrane. Nanoelectropulse perturbation of
      mammalian cells causes translocation of phosphatidylserine (PS) to the outer face
      of the cell, intracellular calcium release, and in some cell types a subsequent
      progression to apoptosis. Experimental observations and molecular dynamics (MD)
      simulations of membranes in pulsed electric fields presented here support the
      hypothesis that nanoelectropulse-induced PS externalization is driven by the
      electric potential that appears across the lipid bilayer during a pulse and is
      facilitated by the poration of the membrane that occurs even during pulses as
      brief as 3 ns. MD simulations of phospholipid bilayers in supraphysiological
      electric fields show a tight association between PS externalization and membrane
      pore formation on a nanosecond time scale that is consistent with experimental
      evidence for electropermeabilization and anode-directed PS translocation after
      nanosecond electric pulse exposure, suggesting a molecular mechanism for
      nanoelectroporation and nanosecond PS externalization: electrophoretic migration
      of the negatively charged PS head group along the surface of nanometer-diameter
      electropores initiated by field-driven alignment of water dipoles at the membrane
      interface.

PMID- 17200600
TI  - Capacitance fluctuations causing channel noise reduction in stochastic Hodgkin
      Huxley systems.
AB  - Voltage-dependent ion channels determine the electric properties of axonal cell
      membranes. They not only allow the passage of ions through the cell membrane, but
      also contribute to an additional charging of the cell membrane resulting in the
      so-called capacitance loading. The switching of the channel gates between an open
      and a closed configuration is intrinsically related to the movement of gating
      charge within the cell membrane. At the beginning of an action potential, the
      transient gating current is opposite to the direction of the current of sodium
      ions through the membrane. Therefore, the excitability is expected to become
      reduced due to the influence of a gating current. Our stochastic Hodgkin-Huxley
      like modeling takes into account both the channel noise-i.e. the fluctuations of
      the number of open ion channels-and the capacitance fluctuations that result from
      the dynamics of the gating charge. We investigate the spiking dynamics of
      membrane patches of a variable size and analyze the statistics of the spontaneous
      spiking. As a main result, we find that the gating currents yield a drastic
      reduction of the spontaneous spiking rate for sufficiently large ion channel
      clusters. Consequently, this demonstrates a prominent mechanism for channel noise
      reduction.

PMID- 17200601
TI  - Mobility of Min-proteins in Escherichia coli measured by fluorescence correlation
      spectroscopy.
AB  - In the bacterium Escherichia coli, selection of the division site involves pole
      to-pole oscillations of the proteins MinD and MinE. Different oscillation
      mechanisms based on cooperative effects between Min-proteins and on the exchange
      of Min-proteins between the cytoplasm and the cytoplasmic membrane have been
      proposed. The parameters characterizing the dynamics of the Min-proteins in vivo
      are not known. It has therefore been difficult to compare the models
      quantitatively with experiments. Here, we present in vivo measurements of the
      mobility of MinD and MinE using fluorescence correlation spectroscopy. Two
      distinct timescales are clearly visible in the correlation curves. While the
      faster timescale can be attributed to cytoplasmic diffusion, the slower timescale
      could result from diffusion of membrane-bound proteins or from protein exchange
      between the cytoplasm and the membrane. We determine the diffusion constant of
      cytoplasmic MinD to be approximately 16 microm(2) s(-1), while for MinE we find
      about 10 microm(2) s(-1), independently of the processes responsible for the
      slower time-scale. The implications of the measured values for the oscillation
      mechanism are discussed.

PMID- 17200602
TI  - Active gels: dynamics of patterning and self-organization.
AB  - The actin cytoskeleton is an active gel which constantly remodels during cellular
      processes such as motility and division. Myosin II molecular motors are involved
      in this active remodeling process and therefore control the dynamic self
      organization of cytoskeletal structures. Due to the complexity of in vivo
      systems, it is hard to investigate the role of myosin II in the reorganization
      process which determines the resulting cytoskeletal structures. Here we use an in
      vitro model system to show that myosin II actively reorganizes actin into a
      variety of mesoscopic patterns, but only in the presence of bundling proteins. We
      find that the nature of the reorganization process is complex, exhibiting
      patterns and dynamical phenomena not predicted by current theoretical models and
      not observed in corresponding passive systems (excluding motors). This system
      generates active networks, asters and even rings depending on motor and bundling
      protein concentrations. Furthermore, the motors generate the formation of the
      patterns, but above a critical concentration they can also disassemble them and
      even totally prevent the polymerization and bundling of actin filaments. These
      results may suggest that tuning the assembly and disassembly of cytoskeletal
      structures can be obtained by tuning the local myosin II concentration/activity.

PMID- 17200603
TI  - Validation of an algorithm for delay stochastic simulation of transcription and
      translation in prokaryotic gene expression.
AB  - The quantitative modeling of gene transcription and translation requires a
      treatment of two key features: stochastic fluctuations due to the limited copy
      numbers of key molecules (genes, RNA polymerases, ribosomes), and delayed output
      due to the time required for biopolymer synthesis. Recently proposed algorithms
      allow for efficient simulations of such systems. However, it is critical to know
      whether the results of delay stochastic simulations agree with those from more
      detailed models of the transcription and translation processes. We present a
      generalization of previous delay stochastic simulation algorithms which allows
      both for multiple delays and for distributions of delay times. We show that delay
      stochastic simulations closely approximate simulations of a detailed
      transcription model except when two-body effects (e.g. collisions between
      polymerases on a template strand) are important. Finally, we study a delay
      stochastic model of prokaryotic transcription and translation which reproduces
      observations from a recent experimental study in which a single gene was
      expressed under the control of a repressed lac promoter in E. coli cells. This
      demonstrates our ability to quantitatively model gene expression using these new
      methods.

PMID- 17200604
TI  - Collective effects in ciliar arrays.
AB  - Collective effects in one-dimensional ciliar arrays are studied analytically and
      numerically. A new phase oscillator description for ciliar motion is introduced
      which depends only on a single parameter. It allows the systematic study of
      hydrodynamic interactions between cilia exhibiting arbitrary beating patterns. It
      is shown that if the hydrodynamic interactions do not alter the beating pattern
      of the cilia no synchronization of ciliar motion occurs. This is in particular
      the case in arrays with low ciliar densities. But hydrodynamic interactions can
      lead to formation of a collective (metachronal) wave which is stable for periodic
      boundary conditions. In finite arrays free boundaries destroy this collective
      motion. The dispersion relation for metachronal waves is found to be non
      universal, i.e., to depend crucially on the microscopic details of the ciliar
      beating pattern.

PMID- 17200605
TI  - Computer-aided design of modular protein devices: Boolean AND gene activation.
AB  - Many potentially useful synthetic gene networks require the expression of an
      engineered gene if and only if two different DNA-binding proteins exist in
      sufficient concentration. While some natural and engineered systems activate gene
      expression according to a logical AND-like behavior, they often utilize
      allosteric or cooperative protein-protein interactions, rendering their
      components unsuitable for a toolbox of modular parts for use in multiple
      applications. Here, we develop a quantitative model to demonstrate that a small
      system of interacting fusion proteins, called a protein device, can activate an
      engineered gene according to the Boolean AND behavior while using only modular
      protein domains and DNA sites. The fusion proteins are created from
      transactivating, DNA-binding, non-DNA binding, and protein-protein interaction
      domains along with the corresponding peptide ligands. Using a combined kinetic
      and thermodynamic model, we identify the characteristics of the molecular
      components and their rates of constitutive production that maximize the fidelity
      of AND behavior. These AND protein devices facilitate the creation of complex
      genetic programs and may be used to create gene therapies, biosensors and other
      biomedical and biotechnological applications that turn on gene expression only
      when multiple DNA-binding proteins are simultaneously present.

PMID- 17200606
TI  - [Not inferior, is it?].

PMID- 17200607
TI  - Reports by some massage therapists of a sense of 'special connection' that is
      sometimes experienced with clients/patients.
AB  - BACKGROUND: The aim of this study was to provide exploratory qualitative data on
      anecdotal reports by some physical therapists that they sometimes experience a
      sense of 'special connection' with patients or clients. PARTICIPANTS AND METHODS:
      21 self-selected massage therapists provided written comments about their
      experience of therapy in response to a questionnaire (free-form response format)
      asking about the experience of connection. RESULTS: 20 out of 21 therapists
      reported a sense of 'special connection'. Content analysis suggested 10 themes,
      the main ones relating to the special connection being: (a) a sense of oneness or
      unity with the patient; (b) intimacy, trust and the touching of souls; (c)
      meditative, trance-like, floating relaxation; (d) 2-way flow of energy, and the
      mutual contribution of patient and therapist characteristics in forming this
      connection; (e) that it tends to be there or not but if there, it varies in
      degree. CONCLUSION: These reports are similar in some respects to descriptions
      given by healers of the experience of healing, suggesting that some massage
      therapists, and possibly some other complementary or conventional therapists
      engage, unknowingly, in a process of healing while they practice the therapy for
      which they have been trained.

PMID- 17200608
TI  - Teaching complementary and alternative medicine in a reform curriculum.
AB  - BACKGROUND: The increasing utilization of complementary and alternative medicine
      (CAM) contrasts with a lack of CAM in medical school education. Therefore, CAM
      therapies were introduced to the Charite University Medical School (Berlin,
      Germany) reform curriculum. METHODS AND RESULTS: Teaching concept: A CAM seminar
      provides basic knowledge about naturopathy, homeopathy, and Traditional Chinese
      medicine (TCM), plus their utilization, empirical research, and underlying
      philosophies. Experiential and dialogical didactic techniques are employed.
      EVALUATION: Students evaluated one of the seminars using the 'Heidelberg
      Inventory for Educational EVALUATION' (Heidelberger Inventar zur
      Lehrveranstaltungs-EVALUATION, HILVE). Student participation and classroom
      atmosphere were rated as very good. All other categories were rated above
      average, except workload and excessive demands. Demand for Education: 69% of all
      3rd- and 7th-semester students (n = 74) answered a questionnaire about their
      opinions on CAM, and the extent and sources of their knowledge. Acupuncture and
      homeopathy were the best-known methods, primarily from courses or seminars.
      Personal experience with CAM was reported by 44% of the students. Depending on
      the method 73-96% of the respondents supported the inclusion of CAM therapies
      into the medical school curriculum. Acknowledged advantages of CAM were its use
      as an alternative or additional treatment (73-82%), fewer side effects (44%), and
      cost reduction (37%). DISCUSSION: The presented concept helps medical students
      develop a reflected opinion on CAM. The students rated the quality of the seminar
      as above average. The high support for university CAM education reflects the
      students' desire for more knowledge. Interest in other philosophies of disease
      and therapy may prepare them for a more integrative and pluralistic approach to
      medicine.

PMID- 17200609
TI  - [Differences between patients of conventional and anthroposophic family
      physicians].
AB  - BACKGROUND: In Germany, complementary medicine, including anthroposophic
      medicine, is becoming increasingly popular. As a consequence, there is an
      increasing need to confirm the benefits of such treatment approaches by
      scientific studies. Knowledge about patients who choose either conventional or
      complementary medicine is basic for any controlled study in this field. PATIENTS
      AND METHODS: 800 patients from 4 anthroposophic (group A) and 4 matched
      conventional family practitioners (group S) filled out two questionnaires.
      Questionnaire 1 included questions on patients' social and health status.
      Questionnaire 2 was a standardized personality inventory test on beliefs about
      personal control over health. RESULTS: Group A had more female patients than
      group S, but there were no differences in age. Also, the proportion of patients
      with a university degree was higher in group A. Of group A, only half as many
      patients as of group S reported to be smokers or overweight. Concerning patients'
      sporting activities the groups showed no differences. In group S, 52% of patients
      suffered from a chronic disease, in group A, 59%. Patients of both groups wanted
      more consultation time, although patients of group A already spent more time with
      their physician than patients of group S. In group A, twice as many patients as
      in group S believe that their lifestyle has an impact on their health, but in
      both groups only 15% behave accordingly. Both groups judge the importance of the
      doctor equal. More than half of all patients wish they can use both complementary
      and conventional therapies. CONCLUSION: Patients of conventional and
      anthroposophic physicians are comparable in many aspects. Anthroposophic patients
      specifically choose their practitioner and treatment and require longer
      consultation time, although they do not expect better treatment results.

PMID- 17200610
TI  - The supply of complementary and alternative medicine in Swiss hospitals.
AB  - OBJECTIVES: Over the past few years, a considerable increase in complementary and
      alternative medicine (CAM) has been observed, particularly in primary care. In
      contrast little is known about the supply of CAM in Swiss hospitals. This study
      aims at the investigation of amount and structure of CAM activities of Swiss
      hospitals. MATERIALS AND METHODS: We designed a cross-sectional survey using a 2
      step, questionnaire- based approach acquiring overview information form hospital
      managers in a first questionnaire leading to detailed information on CAM usage at
      medical department level (head of department). This second questionnaire provides
      data of physician-based and non-physician-based CAM supply. RESULTS: The size of
      hospitals was significantly associated with the provision of CAM. 33% of the
      hospital managers indicated 1 or more medical doctor (MD) using CAM in their
      hospital compared to 37% of confirmation on department level (Kappa value 0.5).
      Mostly different CAM methods were applied. Acupuncture was used most frequently.
      However only 13 hospitals (11%) occupied more than 3 CAM MDs and only 5 hospitals
      had more than 2 full-time equivalents for MDs. Furthermore, 74.7% of these
      personnel resources were dedicated for outpatient care. In terms of CAM methods
      anthroposophic medicine accounted for more than half of the total personnel
      costs. On the other hand usage of non-physician based CAM accounted for 41%
      according to hospital managers compared to 64% of CAM usage according to medical
      departments (Kappa values 0.31). Reflexology of the foot was used most
      frequently. CONCLUSION: Total supply of CAM in Swiss hospitals is low and
      concentrates on few hospitals. Acupuncture is the widest spread discipline but
      anthroposophic medicine spends the most resources. The study shows that a high
      patient demand for CAM faces low supply in hospitals.

PMID- 17200611
TI  - [Acupuncture--needle-pricking within a complex intervention].
AB  - The results of the large acupuncture studies initiated by the German Federal
      Committee of Physicians and Health Insurers raised several new questions
      concerning acupuncture effects. Based on the current evidence it is postulated
      that not yet entirely defined specific und unspecific factors contribute to
      outcome in acupuncture treatment. Consequently, acupuncture has to be regarded as
      a 'complex intervention' consisting of several components. A phased approach to
      evaluate 'complex intervention' is presented and transferred to acupuncture
      research. According to this phased approach unspecific factors contributing to
      acupuncture effects have to be identified and increasingly considered in future
      acupuncture research. Thus, several research methods to identify and evaluate
      unspecific acupuncture effects are suggested, e.g. qualitative methods.
      Therefore, the particular German situation of acupuncture, provided by physicians
      and state-licensed non-medical therapists ('Heilpraktiker'), is taken into
      account. Furthermore, it is discussed to what extent unspecific acupuncture
      effects can be assessed within randomized controlled trials.

PMID- 17200612
TI  - Reporting data on homeopathic treatments (RedHot): a supplement to CONSORT*.
AB  - When homeopathy is tested in clinical trials, understanding and appraisal are
      likely to be improved if published reports contain details of prescribing
      strategies and treatments. An international Delphi panel was convened to develop
      consensus guidelines for reporting homeopathic methods and treatments. The panel
      agreed 28 treatment- and provider-specific items that supplement the CONSORT
      (Consolidated Standards of Reporting Trials) Statement items 2, 3, 4 and 19. The
      authors recommend these for adoption by authors and journals when reporting
      trials of homeopathy.

PMID- 17200613
TI  - [Homeopathy in [corrected] spontaneous bacterial peritonitis].
AB  - The case of a 44-year-old patient with spontaneous bacterial peritonitis caused
      by E. coli is described and discussed. The patient with hypalbuminemia, ascites,
      a medical history of chronic pancreatitis, chronic alcohol abuse and a
      duodenopancreatectomy 6 months before showed a very slow response to conventional
      treatment but a good response to homeopathic therapy with Arsenicum album C200
      and Pulsatilla C200. The discussion focuses on the methodology of single case
      evaluations according to cognition based medicine.

PMID- 17200615
TI  - EDs in crisis.

PMID- 17200614
TI  - Induction of the interferon-inducible RNA-degrading enzyme, RNase L, by stress
      inducing agents in the human cervical carcinoma cells.
AB  - RNA-degradation is one of the fundamental mechanisms of interferon (IFN)
      inducible antiviral response in mammalian cells. This is primarily brought about
      by the IFN-inducible 2',5'-oligoadenylate (2-5A)-cofactor dependent ribonuclease
      L (RNase L). RNase L also functions as a tumor suppressor gene in case of
      prostate cancer due to its role in apoptosis. We report that RNase L is induced
      by stress-inducing agents such as double-stranded RNA [poly(I:C)],
      chemotherapeutic drugs, hydrogen peroxide (H(2)O(2)), calcium chloride (CaCl(2))
      and tumor necrosis factor-alpha (TNF) in the human cervical carcinoma (HeLa)
      cells. The level of RNase L was not detected in the untreated cells. Induction of
      RNase L by such stress-inducing agents correlated with degradation of cellular
      RNA, fragmentation of chromatin-DNA and induction of apoptosis. We checked the
      stress-inducible transcription factor, nuclear factor kappa B (NF-kappaB), which
      was persistently activated by cycloheximide but not by other agents after 24
      hours indicating no role of NFkappaB in the RNase L-induction. However, as
      expected, TNF-induced NF-kappaB activity was stimulated within 10-30 minutes
      through degradation of IkappaB-alpha. Our results strongly suggest that the IFN
      inducible RNase L is induced by a broad range of stress-inducing signals such as
      double-stranded RNA (dsRNA) produced during viral infection, membrane- and
      osmotic shock caused by CaCl(2) and oxidative stress induced by H(2)O(2),
      inflammation stimulated by TNF-alpha and chemotherapy. Thus, in addition to its
      antiviral function, the IFN-inducible RNase L may play an important role during
      stress-response through RNA-degradation and apoptosis.

PMID- 17200616
TI  - Are we ready yet? A nurse asks all nurses to take a stand against the war in
      Iraq.

PMID- 17200617
TI  - Katrina's nurses: murderers?

PMID- 17200619
TI  - Stillbirth and newborn death.

PMID- 17200629
TI  - Nursing gets attention from philanthropists.

PMID- 17200630
TI  - How many red flags does it take?

PMID- 17200631
TI  - Book of the year awards 2006.

PMID- 17200632
TI  - A losing battle. America's broken health care system cost one woman her life.
      Interview by Julie Winokur.

PMID- 17200633
TI  - Helping Hands Health Center.

PMID- 17200634
TI  - SSRIs and the syndrome of inappropriate antidiuretic hormone secretion.
AB  - Selective serotonin reuptake inhibitors, which include some of the mostly widely
      prescribed drugs in the United States, produce fewer adverse effects than other
      types of antidepressants. But their use can be associated with disruption of the
      action of antidiuretic hormone in the body, which wreaks havoc with homeostasis.
      This may lead to the syndrome of inappropriate antidiuretic hormone secretion
      (SIADH), which is characterized by hyponatremia, a potentially fatal condition
      that is typically asymptomatic until it becomes severe. SIADH is more likely in
      some populations, including people who are elderly or who take diuretics. Serum
      sodium levels should be monitored closely in those at higher risk.

PMID- 17200636
TI  - The ABCs of CPR--again.
AB  - Survival rates for cardiac arrests that occur in hospitals and outside them
      continue to be low (17% and 6%, respectively), and fewer than one-third of
      patients who have an out-of-hospital cardiac arrest receive cardiopulmonary
      resuscitation (CPR). Consequently, a number of changes were made to the 2005
      American Heart Association Guidelines for Cardiopulmonary Resuscitation and
      Emergency Cardiovascular Care. The changes were intended to simplify CPR in order
      to increase its use and effectiveness by both clinicians and nonprofessionals.
      This article summarizes the primary changes to the recommendations, including a
      universal 30-to-2 compression-to-ventilation ratio for all lone rescuers, the
      need for compressions of sufficient depth and number, and the replacement of the
      three-shock model of initial defibrillation with one that recommends a single
      shock, now seen as an adequate precursor to CPR.

PMID- 17200649
TI  - Travel job focus.

PMID- 17200650
TI  - True mental health parity.

PMID- 17200651
TI  - Letters from Iraq. Always be ready.

PMID- 17200652
TI  - A subtle shift. How will you know when you've found your calling?

PMID- 17200653
TI  - Light-induced changes in protein nitration in photoreceptor rod outer segments.
AB  - PURPOSE: Light has been shown to modulate protein nitration in rat retinas. To
      better understand the role of protein nitration in photoreceptor cell death
      induced by intense light, we examined retinal protein nitration and identified
      target proteins in rod outer segments (ROS). METHODS: Cyclic light-reared rats,
      treated or not with the antioxidant, dimethylthiourea (DMTU), were exposed to
      intense green light for 8 h. A subset of these rats was kept in the dark for 24 h
      after 8 h of light exposure. Western analysis of ROS proteins with an anti
      nitrotyrosine antibody was performed to examine changes in protein nitration. 2D
      immunoblots with anti-nitrotyrosine antibody followed by liquid chromatography
      tandem mass spectrometry was used to identify nitrated proteins in ROS. The
      expression levels of three nitric oxide synthase (NOS) isoforms, inducible,
      neuronal-, and endothelial-NOS were semi-quantified by immunoblot analysis.
      RESULTS: Western analysis revealed that the level of ROS protein nitration
      increased during the dark recovery period after 8 h of light treatment in both
      DMTU treated and untreated rats. However, DMTU effectively reduced protein
      nitration in ROS during light exposure and during the subsequent dark recovery
      period. Using 2D-immunoblotting followed by liquid chromatography tandem mass
      spectrometry analysis, we identified ten ROS proteins as nitration targets. Most
      of these proteins were glycolytic enzymes. The level of inducible-NOS in the
      retina was increased by light exposure. CONCLUSIONS: The effect of DMTU in
      reducing ROS protein nitration during and after light suggests the involvement of
      protein nitration during light-induced photoreceptor cell death. Nitration of
      glycolytic enzymes specifically may alter their activities. Increased levels of
      iNOS during and after intense light exposure suggest that this isoform is
      responsible for intense light induced protein nitration in ROS during the dark
      recovery period. The limited nitration seen in ROS during light exposure may
      reflect a quenching effect by endogenous antioxidants on the generation of
      reactive oxygen and nitrogen species.

PMID- 17200654
TI  - Rapid detection of SAG 926delA mutation using real-time polymerase chain
      reaction.
AB  - PURPOSE: Mutation 926delA of the arrestin/S-antigen SAG gene is the main cause of
      Oguchi disease in the Japanese. The purpose of this study was to develop a rapid
      diagnostic assay to detect mutations in the SAG gene. METHODS: Two sequence
      specific primers and fluorophore-labeled probes for exon 11 of the SAG gene were
      designed, and the region spanning the mutations was amplified by polymerase chain
      reaction (PCR) using the LightCycler detection system (Roche Diagnostics,
      Mannheim, Germany). The mutations were then identified by melting curve analyses
      of the hybrid formed between the PCR product and a specific fluorescent probe.
      RESULTS: We clearly distinguished each SAG genotype (homozygous and heterozygous
      926delA and wild type) by the distinct melting peaks at different temperatures.
      One thermal cycling required approximately 54 min to process, and the results
      were 100% in concordance with the genotypes determined by DNA sequencing.
      CONCLUSIONS: We have succeeded in developing a rapid method to detect the most
      frequent mutation in the SAG gene. This method will help in identifying gene
      mutations associated with Oguchi disease with a rapid and reliable identification
      or the exclusion of the frequent mutations in the SAG gene.

PMID- 17200655
TI  - Novel triple missense mutations of GUCY2D gene in Japanese family with cone-rod
      dystrophy: possible use of genotyping microarray.
AB  - PURPOSE: To report a novel mutation in the GUCY2D gene in a Japanese family with
      autosomal dominant cone-rod dystrophy (adCORD), and to examine the possible use
      of arrayed primer extension (APEX)-based genotyping chip in detecting mutations.
      METHODS: Genomic DNA was extracted from the peripheral blood of family members
      with adCORD. It was PCR-amplified, fragmented, and hybridized to APEX-based
      genotyping microarrays on which known disease-associated sequence variations were
      arrayed for patients with early-onset retinal dystrophy. All coding exons of the
      GUCY2D gene were directly sequenced. The PCR amplicon carrying a novel mutation
      was subcloned, and each clone was sequenced. RESULTS: Five single nucleotide
      polymorphisms in AIPL1, RPGRIP1, and GUCY2D were detected in the proband by
      microarray screening, and all were validated by direct sequencing. A novel
      heterozygous triple missense mutation of c.2540_2542delinsTCC
      (p.Gln847_Lys848delinsLeuGln amino acid substitutions) was found in both the
      proband and his father, and the three nucleotide changes were located on the same
      chromosome. Electroretinography (ERGs) demonstrated a significant reduction in
      rod function and a complete absence of cone function in both affected
      individuals. CONCLUSIONS: A novel heterozygous triple consecutive missense
      mutation in the GUCY2D gene has been linked to adCORD. Our study demonstrates
      that the APEX-based gene screening can be used to identify simultaneously disease
      modifying sequence changes as well as disease-causing mutations, once proper and
      comprehensive sites of sequence variations of the disease are arrayed.

PMID- 17200657
TI  - Effect of photoreceptor degeneration on RNA splicing and expression of AMPA
      receptors.
AB  - PURPOSE: Glutamate is the most important neurotransmitter for excitatory
      synapses, and its ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptor is widely expressed in the vertebrate retina. AMPA receptors
      are hetero-oligomers composed of subsets of four distinct subunits termed GluR1
      4. This study was conducted to examine the developmental progression of the flip
      to-flop alternative splicing switch of AMPA receptors in wild-type and rd mouse
      retina. METHODS: The flop:flip ratio and expression levels of GluR1-4 from
      postnatal day 8 (P8) to P40 were calculated using quantitative real-time
      polymerase chain reaction (PCR) analysis and immunoblot analysis. The time course
      of photoreceptor degeneration in rd mice was histologically analyzed. RESULTS: In
      wild-type mouse retina, the flop:flip ratio in GluR1, but not GluR2-4,
      dramatically increased between P16 and P20. In rd mice, photoreceptor
      degeneration progressed from P10 to P20. GluR1 flop:flip ratio in rd mice was
      normal compared with wild-type mice before P16, however, the dramatic increase
      between P16 and P20 was completely suppressed. The suppression in the later phase
      of retinal degeneration was specific to GluR1 and was not observed in GluR2-4.
      Moreover, the expression levels of GluR1, GluR3, and GluR4 were increased in rd
      mice. CONCLUSIONS: These results suggest that the inherited form of photoreceptor
      degeneration in rd mice contributes to the regulation of the flip-to-flop exon
      switch in GluR1 and the expression levels of AMPA receptors.

PMID- 17200658
TI  - Conjunctival expression of thymosin-beta4 in vernal keratoconjunctivitis.
AB  - PURPOSE: Thymosin-beta4 (Tbeta4) is a small actin-sequestrating peptide that
      modulates inflammation and healing in different tissues. The aim of this study
      was to investigate the molecular and biochemical expression of Tbeta4 in the
      healthy conjunctiva and in the conjunctiva of patients with vernal
      keratoconjunctivitis (VKC), a severe allergic eye disease characterized by
      chronic inflammation and marked tissue remodeling. METHODS: Conjunctival tissues,
      obtained from seven VKC patients and five sex/age-matched healthy subjects, were
      evaluated for Tbeta4 expression by relative real time-PCR and light/confocal
      microscopy. The distribution patterns of Tbeta4 in conjunctival sections as well
      as Tbeta4 expression by mast cells (AA1), eosinophils (EG2), and
      fibroblast/myofibroblasts (Thy1/alpha-SMA) in VKC tissues was also evaluated by
      double immunofluorescence. RESULTS: Compared to healthy specimens, Tbeta4 mRNA
      appeared upregulated in VKC conjunctival biopsies as detected by real-time PCR.
      In the healthy conjunctiva, Tbeta4 protein expression was confined to the
      conjunctival epithelium, while a weak staining was observed in the stroma. In VKC
      conjunctival sections, Tbeta4 immunoreactivity was selectively increased in the
      stroma where, by confocal analysis of VKC papillary formations, Tbeta4 appeared
      to be mostly localized in eosinophils and activated fibroblasts/myofibroblasts.
      CONCLUSIONS: Our data provides the first evidence of Tbeta4 expression in the
      conjunctival tissues. The upregulation of both Tbeta4 mRNA and protein in the
      conjunctival stroma, and its peculiar localization in eosinophils and
      myofibroblasts populating VKC lesions, suggest a possible role for Tbeta4 in
      tissue inflammation and remodeling occurring in VKC.

PMID- 17200656
TI  - Interphotoreceptor retinoid-binding protein gene structure in tetrapods and
      teleost fish.
AB  - PURPOSE: The interphotoreceptor retinoid-binding protein (IRBP) gene possesses an
      unusual structure, encoding multiple Repeats, each consisting of about 300 amino
      acids. Our goals were to gain insight into the function of IRBP, and to test the
      current model for the evolution of IRBP, in which Repeats were replicated from a
      simpler ancestral gene. METHODS: We employed a bioinformatics approach to analyze
      IRBP loci in recently completed or near-complete genome sequences of several
      vertebrates and nonvertebrate chordates. IRBP gene expression in zebrafish was
      evaluated by reverse transcriptase PCR (RT-PCR) and in situ mRNA hybridizations
      with gene-specific probes. RESULTS: Patterns of exons and introns in the IRBP
      genes of tetrapods were highly similar, as were predicted amino acid sequences
      and Repeat structures. IRBP gene structure in teleost fish was more variable, and
      we report a new gene structure for two species, the Japanese puffer fish
      (Takifugu rubripes) and the zebrafish (Danio rerio). These teleost genomes
      contain a two-gene IRBP locus arranged head-to-tail in which the first gene, Gene
      1, is intronless and contains a single large exon encoding three complete
      Repeats. It is followed by a second gene, Gene 2, which corresponds to the
      previously reported gene consisting of two Repeats spread across four exons and
      three introns. Each of the two zebrafish genes is transcribed. Gene 2 is
      expressed in the photoreceptors and RPE, and Gene 1 is expressed in the inner
      nuclear layer and weakly in the ganglion cell layer. CONCLUSIONS: The tetrapod
      IRBP gene structure is highly conserved while the teleost fish gene structure was
      a surprise: It appears to be a two-gene locus with distinct Repeat organization
      in each open reading frame. This gene structure and gene expression data are
      consistent with possible neofunctionalization or sub-function partitioning of
      Gene 1 and Gene 2 in the zebrafish. We suggest that the two-gene locus in teleost
      fish arose as a consequence of either the known whole genome duplication or
      single gene tandem duplication.

PMID- 17200659
TI  - Tyrosinase gene family and Vogt-Koyanagi-Harada disease in Japanese patients.
AB  - PURPOSE: The aim of the present study was to examine the genetic background of
      Vogt-Koyanagi-Harada (VKH) disease in a Japanese population by analyzing the
      tyrosinase gene family (TYR, TYRP1, and dopachrome tautomerase (DCT)). METHODS:
      87 VKH patients and 122 healthy controls were genotyped using seven
      microsatellite markers on the candidate loci. We analyzed microsatellite (MS)
      polymorphisms at regions within tyrosinase gene family loci. In addition, the
      haplotype frequencies were also estimated and statistical analysis was performed.
      HLA-DRB1 genotyping was performed by the PCR-restriction fragment length
      polymorphism (RFLP) method. RESULTS: No significant evidence for an association
      was found. HLA-DRB1*0405 showed a highly significant association with VKH disease
      compared with the healthy controls (Pc=0.000000079), as expected. CONCLUSIONS: We
      concluded that there is no genetic susceptibility or increased risk attributed to
      the tyrosinase gene family. Our results suggest the need for further genetic
      study and encourage a search for novel genetic loci and predisposing genes in
      order to elucidate the genetic mechanisms underlying VKH disease.

PMID- 17200660
TI  - Sorbitol causes preferential selection of Muller glial precursors from late
      retinal progenitor cells in vitro.
AB  - PURPOSE: The replacement of glucose by sorbitol in growth medium causes selection
      of astroglial cells from heterogeneous primary cultures derived from the brains
      of newborn mice. The present study was undertaken to investigate the effects of
      sorbitol on in vitro selection of Muller glial precursors from expanded late
      retinal progenitor cells (RPCs). METHODS: RPCs used in these studies were
      isolated from the neural retina of postnatal day one green fluorescent protein
      (GFP) transgenic mice. The resulting GFP positive neurospheres were dissociated
      into a single cell suspension and grown on poly-D-lysine/laminin coated tissue
      culture flasks or slides to generate adherent RPCs. These adherent cells were
      treated with glucose free medium containing 25 mM sorbitol for 7 days and the
      expression of retinal-specific cell markers was determined by
      immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and
      immunoblot analysis RESULTS: In vitro studies showed that sorbitol treatment of
      late RPCs altered cellular morphology. Immunocytochemical studies showed an
      increase in the proportion of cells expressing glial cell markers, most of which
      co-expressed CRALBP, GFAP, and vimentin. An increase in the proportion of cells
      expressing PKCalpha, a bipolar cell marker, was also observed. RT-PCR analysis
      showed down-regulation of nestin transcripts with a concomitant increase in
      CRALBP, GFAP, vimentin and PKCalpha. These findings were confirmed by immunoblot
      analysis, where down-regulation of nestin expression with simultaneous up
      regulation of CRALBP, GFAP and PKCalpha was observed. CONCLUSIONS: Sorbitol
      treatment of multipotent late RPCs, in the absence of glucose, results in the
      preferential selection of Muller glial precursors and their subsequent
      differentiation into cells that morphologically resemble Muller cells and co
      express multiple glial markers.

PMID- 17200661
TI  - Molecular changes in selected epithelial proteins in human keratoconus corneas
      compared to normal corneas.
AB  - PURPOSE: The purpose of the study was to determine molecular changes in selected
      epithelial proteins in human keratoconus (KC) corneas compared to normal corneas.
      METHODS: Two-dimensional (2-D) gel electrophoretic profiles of epithelial cell
      proteins from normal and keratoconus corneas were compared, and the selected
      protein spots that showed either up- or downregulation were identified. The
      desired spots were identified after trypsin digestion and mass spectrometric
      analysis. Based on the results, two proteins, alpha-enolase and beta-actin, were
      further analyzed by immunohistochemical and western blot methods, using
      respective antibodies. To determine the presence of mRNA of the two proteins in
      the epithelial cells, RT-PCR studies were performed. RESULTS: On comparison of
      the 2-D gel electrophoretic protein profiles, two protein spots were identified
      in normal corneas that were either absent or present at lower levels in
      keratoconus corneas. The two spots were determined to be alpha-enolase (48 kDa)
      and beta-actin (42 kDa) by matrix-assisted laser desorption ionization-time of
      flight (MALDI-TOF), and ES-MS/MS mass spectrometric methods. Immunohistochemical
      analysis revealed that alpha-enolase and beta-actin were present at extremely low
      levels in the epithelial superficial and wing cells of the keratoconus corneas
      compared to these cells of normal corneas. 2-D gel electrophoresis followed by
      western blot analysis revealed relatively greater degradation of the two proteins
      in the keratoconus corneas compared to normal corneas. RT-PCR analysis showed the
      mRNA expression of the two proteins in the epithelial cells of both normal and
      keratoconus corneas. CONCLUSIONS: The results showed relatively low or negligible
      levels of alpha-enolase and beta-actin in the wing and superficial epithelial
      cells of keratoconus corneas compared to normal corneas. This was attributed to
      relatively greater degradation of the two proteins in keratoconus corneas
      compared to normal corneas.

PMID- 17200662
TI  - Progressive sutural cataract associated with a BFSP2 mutation in a Chinese
      family.
AB  - PURPOSE: To identify the mutation underlying the segregation of progressive
      sutural congenital cataracts in a four-generation Chinese pedigree. METHODS:
      Genomic DNA was extracted from the peripheral blood samples of members of the
      pedigree. A genome-wide scan was performed using microsatellite markers spaced at
      about 10 cM intervals. Linkage analysis was carried out using a Linkage software
      package. Ten additional microsatellite markers for the positive region were
      selected for precise targeting, and haplotype data were processed using Cyrillic
      software to define the region of the disease gene. Mutation detection was carried
      out by sequencing candidate genes. RESULTS: Significant evidence of linkage was
      obtained at marker D3S1279 (LOD score [Z] =2.32, recombination fraction
      [theta]=0.0). Precise targeting and haplotype analysis traced the disease gene to
      a 38.6 cM region bounded by D3S1267 and D3S1614 at 3q21.1- q26.2 near BFSP2,
      which encodes a lens-specific beaded filament protein. Sequencing results
      revealed a 3-bp deletion of nucleotides 696-698 (GAA) in exon 3 of BFSP2, which
      is predicted to cause an in-frame deletion of glutamic acid residue 233 from the
      polypeptide encoded by the mutant gene. This deletion was seen neither in any
      unaffected member of the family nor in 50 unrelated control individuals.
      CONCLUSIONS: We observed progressive isolated sutural cataract associated with a
      deletion mutation of the BFSP2 gene in a Chinese pedigree. It highlights the
      physiological importance of the beaded filament protein and supports the role of
      BFSP2 in human cataract formation.

PMID- 17200664
TI  - Gene expression profile of the adult human retinal ganglion cell layer.
AB  - PURPOSE: Pathophysiological events in the retinal ganglion cell layer (GCL) are a
      prominent feature of several optic neuropathies including glaucoma. The purpose
      of this study was to identify and catalog genes whose expression in the human
      retina is restricted to the GCL. METHODS: Laser capture microdissection (LCM)
      technology was used to isolate tissue from the perimacular retina of three human
      donors without retinal or optic nerve disease. RNA was isolated from the (1)
      retinal GCL and (2) the inner and outer nuclear layers of the same retina, and
      the gene expression profiles of both fractions were determined using Affymetrix
      Hu133Plus 2.0 GeneChips. Data were analyzed to identify those genes whose
      expression is substantially more prevalent in the GCL when compared to the outer
      retinal layers. Differential expression of selected genes was confirmed by real
      time PCR and immunohistochemistry. RESULTS: The results show that mRNA levels of
      previously described ganglion cell markers, e.g. the neurofilament genes (NEFH,
      NEF3, or NEFL) and the Brn3a transcription factor (POU4F1), were highly enriched
      in the isolated GCL fraction. In contrast, transcripts for genes associated with
      phototransduction (RHO), photoreceptor development (NR2E3), or interphotoreceptor
      matrix constituents (IMPG1) were nearly absent from the GCL fraction. Using
      bioinformatics approaches over 80 genes were identified whose expression in the
      human retina appears to be limited to the GCL. CONCLUSIONS: We have successfully
      used LCM technology to generate gene expression profiles of highly enriched GCL
      fractions of the normal human retina. These data not only provide clues to the
      normal function of retinal ganglion cells but also serve as a resource in the
      development of ganglion cell specific markers or transfection vectors, and the
      identification of candidate genes for hereditary forms of glaucoma.

PMID- 17200663
TI  - Confocal immunolocalization of bovine serum albumin, serum retinol-binding
      protein, and interphotoreceptor retinoid-binding protein in bovine retina.
AB  - PURPOSE: Recently it has been shown that the transport as well as clearance of
      retinol from isolated rod photoreceptors requires an extracellular factor.
      Interphotoreceptor retinoid-binding protein (IRBP) is a component of the
      interphotoreceptor matrix (IPM) and is known to bind visual cycle retinoids.
      Serum albumin and serum retinol-binding protein (sRBP), proteins capable of
      binding retinoids, have also been reported to be components of the IPM. It is of
      interest to know the components present in the IPM that are capable of binding
      visual cycle retinoids and that also facilitate rhodopsin regeneration. The
      purpose of this study was to determine the localization of serum albumin, sRBP,
      and IRBP in bovine retina using immunofluorescence analysis. METHODS: Fresh
      bovine eyes, obtained from a local abattoir, were fixed immediately after
      enucleation. Tissue sections (100 microm) were incubated with primary antibodies
      to bovine serum albumin (BSA), sRBP, and IRBP. Sections were washed then
      incubated 4 h with 4'-6-Diamidino-2-phenylindole (DAPI), Alexa Fluor(R) 488 goat
      antimouse, and Alexa Fluor 568 goat antirabbit secondary antibodies. Sections
      were analyzed using a laser scanning confocal microscope equipped with Nomarski
      optics. Western immunoblot analysis of bovine retinal tissues and protein
      standards was performed using the primary antibodies to BSA, sRBP, and IRBP to
      show specificity to their respective antigens. RESULTS: Immunoblot analysis
      showed that monoclonal anti-BSA was highly specific for BSA detecting only a
      single band at about 67 kDa. Antihuman sRBP and antibovine IRBP were also highly
      specific, recognizing a single band at about 25 and about 133 kDa, respectively.
      No immunopositive bands were observed in bovine neural retinal when probed with
      the anti-sRBP antibody; however, a single immunoreactive band at about 67 and
      about 133 kDa was detected in bovine neural retina by the anti-BSA and IRBP
      antibodies, respectively. Immunofluorescence analysis showed labeling for IRBP
      throughout the IPM. IRBP labeling was especially associated with the outer
      segments of photoreceptors and also with the apical surface of the retinal
      pigment epithelium. Immunofluorescence labeling for serum albumin was associated
      only with the lumen of retinal and choroidal blood vessels. Staining for both
      serum albumin and sRBP in the IPM was negative. CONCLUSIONS: Immunofluorescence
      analysis of fresh bovine eyes using antibodies to BSA and sRBP clearly shows that
      serum albumin and sRBP are not components of bovine IPM. IRBP, on the other hand,
      is localized to the IPM where it is available for the binding and transport of
      visual cycle retinoids. From these data we conclude that serum albumin and sRBP
      are not factors that could participate in the binding as well as transport of
      visual cycle retinoids in the IPM of bovine retina.

PMID- 17200665
TI  - Stimulation of apical and basolateral VEGF-A and VEGF-C secretion by oxidative
      stress in polarized retinal pigment epithelial cells.
AB  - PURPOSE: To investigate whether oxidative stress modulates vascular endothelial
      growth factor (VEGF)-A and VEGF-C expression and polarized secretion in a human
      retinal pigment epithelium cell line (ARPE-19). METHODS: Long-term culture of
      ARPE-19 cells in Dulbecco's modified Eagle medium (DMEM)/F12 containing 1% fetal
      bovine serum (FBS) on transwell filters (12 mm or 6 mm, pore size 0.4 microm) was
      performed to produce polarized retinal pigment epithelium (RPE) monolayers. The
      integrity of polarized monolayer was established by measurement of
      transepithelial resistance (TER) and presence of tight junctions assessed by
      zonula occludens (ZO-1) and occludin expression and apical Na/K ATPase
      localization. Paracellular permeability was studied using radiolabeled mannitol.
      Confluent cells were treated with tertiary butyl hydrogen peroxide (tBH) for
      varying durations (0-5 h) and doses (50-200 microM). VEGF-A and -C expression was
      evaluated by western blot and quantitative RT-PCR, while secretion to the apical
      and basolateral surfaces was quantitated by ELISA. RESULTS: Polarity of ARPE-19
      cells was verified by the localization of tight junction proteins, ZO-1 and its
      binding partner occludin by confocal microscopy as well as by localization of
      Na,K-ATPase at the apical surface. The TER in confluent ARPE-19 cells averaged
      48.7+/-2.1 Omega. cm(2) and tBH treatment (0-5 h) did not alter TER significantly
      (46.9+/-1.9 Omega. cm(2); p>0.05 versus controls) or ZO-1 expression. Whole cell
      mRNA in nonpolarized ARPE-19 increased with tBH at 5 h both for VEGF-A and VEGF-C
      and the increase was significant (p<0.05 vs controls). A similar, maximal
      increase at 5 h tBH treatment was also observed for VEGF-A and VEGF-C cellular
      protein levels. The secretion of VEGF-A and VEGF-C in nonpolarized ARPE showed an
      increase with tBH exposure. The levels of secretion of VEGF-A and -C were
      significantly higher in polarized monolayers and were stimulated significantly
      with tBH at both apical and basolateral domains. The secretion of VEGF-A
      increased with 150 microM of tBH treatment as a function of time (1-5 h) with
      maximal increases at 5 h from 410 to 2080 pg/10(6) cells on the apical and 290 to
      1680 pg/10(6) cells on basolateral domains. The pattern of VEGF-C secretion was
      similar. VEGF-A secretion was dose-dependent for the tBH range of 50-200 microM
      and apical secretion tended to be higher than basolateral secretion. CONCLUSIONS:
      Our data show that oxidative stress to RPE from tBH upregulates secretion of both
      VEGF-A and C. The secretion to the apical side was higher than that of
      basolateral side for VEGF-A and C. Given the role of VEGF in choroidal
      neovascularization, these data may be of value in understanding pathogenic
      mechanisms and designing antiangiogenic therapies.

PMID- 17200666
TI  - Gene expression changes in the retina following optic nerve transection.
AB  - PURPOSE: To obtain and analyze the gene expression profiles of the retina
      following optic nerve transection (ONT). METHODS: An axotomy animal model was
      generated by taking a cross section of the optic nerve with care not to damage
      the adjacent blood supply. The extent of cell loss was evaluated by counting
      cells in the ganglion cell layer (GCL) of flat-mounted retinas stained with
      cresyl violet. Gene expression profiles of control and ONT retinas were analyzed
      with Agilent's rat oligo microarray slides. Differentially expressed genes were
      identified from three independent experiments and clustered based on their
      functions with expression analysis systematic explorer software. Real-time
      quantitative and semiquantitative RT-PCR were used to validate changes in gene
      expression levels. RESULTS: Gene expression changes in axotomized retinas were
      analyzed with rat oligo microarray slides containing 22,575 oligonucleotide
      probes that represent over 20,000 genes and expressed sequence tags (ESTs). The
      expression of 493 genes was increased more than 1.5 fold, including 85 that were
      upregulated more than 2 fold, and the expression of 113 genes was decreased 1.5
      fold or more, including 21 that were downregulated more than 2 fold.
      Differentially expressed genes were clustered based on their functions. Several
      novel genes expressed in the GCL have been identified and their expression
      patterns in different tissues were analyzed. Among the genes differentially
      regulated in retinas with induced retinal ganglion cell (RGC) death, we have
      identified 13 genes that are mapped to known glaucoma loci and can be considered
      for mutation screening in patients with inherited forms of glaucoma. CONCLUSIONS:
      The gene expression profiles of the ONT retinas can be used to identify RGC
      expressed genes, which may be essential for the morphological and physiological
      characteristics of RGCs. The results of this study can also be used to evaluate
      the molecular changes taking place in the retina in response to RGC loss.

PMID- 17200667
TI  - Nucleotide sequence variation within the human tyrosine kinase B neurotrophin
      receptor gene: association with antisocial alcohol dependence.
AB  - To identify sequence variants in genes that may have roles in neuronal responses
      to alcohol, we resequenced the 5' region of tyrosine kinase B neurotrophin
      receptor gene (NTRK2) and determined linkage disequilibrium (LD) values,
      haplotype structure, and performed association analyses using 43 single
      nucleotide polymorphisms (SNPs) covering the entire NTRK2 region in a Finnish
      Caucasian sample of 229 alcohol-dependent subjects with antisocial personality
      disorder (ASPD) and 287 healthy controls. Individually, three SNPs were
      associated with alcohol dependence and alcohol abuse (AD) (P-value from 0.0019 to
      0.0059, significance level was set at P<or=0.01 corrected for multiple testing),
      whereas a common 18 locus haplotype within the largest LD block of NTRK2, a 119
      kb region containing the 5' flanking region and exons 1-15, was marginally
      overrepresented in control subjects compared to AD individuals (global P=0.057).
      Taken together, these results support a role for the NTRK2 gene in addiction in a
      Caucasian population with AD and a subtype of ASPD.

PMID- 17200668
TI  - PALB2, which encodes a BRCA2-interacting protein, is a breast cancer
      susceptibility gene.
AB  - PALB2 interacts with BRCA2, and biallelic mutations in PALB2 (also known as
      FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia. We identified
      monoallelic truncating PALB2 mutations in 10/923 individuals with familial breast
      cancer compared with 0/1,084 controls (P = 0.0004) and show that such mutations
      confer a 2.3-fold higher risk of breast cancer (95% confidence interval (c.i.) =
      1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer
      susceptibility gene and further demonstrate the close relationship of the Fanconi
      anemia-DNA repair pathway and breast cancer predisposition.

PMID- 17200669
TI  - A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility
      variant for Crohn disease in ATG16L1.
AB  - We performed a genome-wide association study of 19,779 nonsynonymous SNPs in 735
      individuals with Crohn disease and 368 controls. A total of 7,159 of these SNPs
      were informative. We followed up on all 72 SNPs with P <or= 0.01 with an allele
      based disease association test in 380 independent Crohn disease trios, 498 Crohn
      disease singleton cases and 1,032 controls. Disease association of rs2241880 in
      the autophagy-related 16-like 1 gene (ATG16L1) was replicated in these samples (P
      = 4.0 x 10(-8)) and confirmed in a UK case-control sample (P = 0.0004). By
      haplotype and regression analysis, we found that marker rs2241880, a coding SNP
      (T300A), carries virtually all the disease risk exerted by the ATG16L1 locus. The
      ATG16L1 gene encodes a protein in the autophagosome pathway that processes
      intracellular bacteria. We found a statistically significant interaction with
      respect to Crohn disease risk between rs2241880 and the established CARD15
      susceptibility variants (P = 0.039). Together with the lack of association
      between rs2241880 and ulcerative colitis (P > 0.4), these data suggest that the
      underlying biological process may be specific to Crohn disease.

PMID- 17200670
TI  - Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo
      methylation in cancer.
AB  - Many genes associated with CpG islands undergo de novo methylation in cancer.
      Studies have suggested that the pattern of this modification may be partially
      determined by an instructive mechanism that recognizes specifically marked
      regions of the genome. Using chromatin immunoprecipitation analysis, here we show
      that genes methylated in cancer cells are specifically packaged with nucleosomes
      containing histone H3 trimethylated on Lys27. This chromatin mark is established
      on these unmethylated CpG island genes early in development and then maintained
      in differentiated cell types by the presence of an EZH2-containing Polycomb
      complex. In cancer cells, as opposed to normal cells, the presence of this
      complex brings about the recruitment of DNA methyl transferases, leading to de
      novo methylation. These results suggest that tumor-specific targeting of de novo
      methylation is pre-programmed by an established epigenetic system that normally
      has a role in marking embryonic genes for repression.

PMID- 17200671
TI  - Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to
      childhood cancer.
AB  - PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic
      BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood
      malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN)
      in seven families affected with Fanconi anemia and cancer in early childhood,
      demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi
      anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of
      childhood cancer.

PMID- 17200672
TI  - Fanconi anemia is associated with a defect in the BRCA2 partner PALB2.
AB  - The Fanconi anemia and BRCA networks are considered interconnected, as BRCA2 gene
      defects have been discovered in individuals with Fanconi anemia subtype D1. Here
      we show that a defect in the BRCA2-interacting protein PALB2 is associated with
      Fanconi anemia in an individual with a new subtype. PALB2-deficient cells showed
      hypersensitivity to cross-linking agents and lacked chromatin-bound BRCA2; these
      defects were corrected upon ectopic expression of PALB2 or by spontaneous
      reversion.

PMID- 17200673
TI  - Epigenetic stem cell signature in cancer.
AB  - Embryonic stem cells rely on Polycomb group proteins to reversibly repress genes
      required for differentiation. We report that stem cell Polycomb group targets are
      up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation
      than non-targets, supporting a stem cell origin of cancer in which reversible
      gene repression is replaced by permanent silencing, locking the cell into a
      perpetual state of self-renewal and thereby predisposing to subsequent malignant
      transformation.

PMID- 17200674
TI  - Role of calcineurin in the regulation of human lung mast cell and basophil
      function by cyclosporine and FK506.
AB  - BACKGROUND AND PURPOSE: Cyclosporine and FK506 are thought to act by targeting
      the Ca2+-dependent protein phosphatase, calcineurin. The aim of the present study
      was to determine whether cyclosporine and FK506 stabilize mast cells and
      basophils by interacting with calcineurin. EXPERIMENTAL APPROACH: The effects of
      cyclosporine and FK506 on the IgE-mediated release of histamine from mast cells
      and basophils were evaluated. The presence of calcineurin in cells was determined
      by Western blotting. Ca2+-dependent protein phosphatase activities were assessed
      in cell extracts using a synthetic phosphorylated peptide that is known to serve
      as a substrate for calcineurin. KEY RESULTS: FK506 was about 100-fold more potent
      than cyclosporine as an inhibitor of IgE-dependent histamine release from mast
      cells and basophils. Immunoblotting of solubilized preparations of purified cells
      demonstrated the presence of calcineurin in mast cells and basophils. In enzyme
      assays, mast cells expressed approximately 7-fold higher Ca2+-dependent protein
      phosphatase activity than basophils. Whereas cyclosporine effectively inhibited
      Ca2+-dependent protein phosphatase activity in cell extracts, FK506 was
      considerably less effective. CONCLUSIONS AND IMPLICATIONS: FK506 and cyclosporine
      inhibit the stimulated release of histamine from mast cells and basophils.
      However, the ability of cyclosporine, but not FK506, to inhibit Ca2+-dependent
      protein phosphatase activity questions whether FK506 stabilizes mast cells and
      basophils by interacting with calcineurin.

PMID- 17200675
TI  - Renal mesangial cells: moving on sphingosine kinase-1.
AB  - Sphingosine kinase-1 (SphK1) catalyses the phosphorylation of sphingosine to
      sphingosine-1-phosphate (S1P), which acts on at least five specific G-protein
      coupled receptors and also intracellularly. SphK1 has been implicated in cell
      proliferation, cancer growth, chemoresistance, immune cell functions and cell
      migration. In this issue of the British Journal of Pharmacology, Klawitter et al.
      demonstrate that extracellular nucleotides stimulate the migration of renal
      mesangial cells. The nucleotides furthermore upregulated SphK1 expression and
      activity, and this enzyme was required for nucleotide-induced migration. Together
      with previous findings, these data raise exciting questions: by which mechanism
      does SphK1 regulate migration in mesangial cells, how is the interplay of
      purinoceptors and S1P receptors organized in these cells, and how would SphK1
      deficient mice respond to kidney damage?

PMID- 17200676
TI  - Extracellular nucleotides induce migration of renal mesangial cells by
      upregulating sphingosine kinase-1 expression and activity.
AB  - BACKGROUND AND PURPOSE: Extracellular nucleotides act as potent mitogens for
      renal mesangial cells (MC). In this study we determined whether extracellular
      nucleotides trigger additional responses in MCs and the mechanisms involved.
      EXPERIMENTAL APPROACH: MC migration was measured after nucleotide stimulation in
      an adapted Boyden-chamber. Sphingosine kinase-1 (SK-1) protein expression was
      detected by Western blot analysis and mRNA expression quantified by real-time
      PCR. SK activity was measured by an in vitro kinase assay using sphingosine as
      substrate. KEY RESULTS: Nucleotide stimulation caused biphasic activation of SK
      1, but not SK-2. The first peak occurred after minutes of stimulation and was
      followed by a second delayed peak after 4-24 h of stimulation. The delayed
      activation of SK-1 is due to increased SK-1 mRNA steady-state levels and de novo
      synthesis of SK-1 protein, and depends on PKC and the classical MAPK cascade. To
      see whether nucleotide-stimulated cell responses require SK-1, we selectively
      depleted SK-1 from cells by using small-interference RNA (siRNA). MC migration is
      highly stimulated by ATP and UTP; this is mimicked by exogenously added S1P.
      Depletion of SK-1 by siRNA drastically reduced the effect of ATP and UTP on cell
      migration but not on cell proliferation. Furthermore, MCs isolated from SK-1
      deficient mice were completely devoid of nucleotide-induced migration.
      CONCLUSIONS AND IMPLICATIONS: These data show that extracellular nucleotides
      besides being mitogenic also trigger MC migration and this cell response
      critically requires SK-1 activity. Thus, pharmacological intervention of SK-1 may
      have impacts on situations where MC migration is important such as during
      inflammatory kidney diseases.

PMID- 17200677
TI  - Effects of etanercept, a tumour necrosis factor-alpha antagonist, in an
      experimental model of periodontitis in rats.
AB  - BACKGROUND AND PURPOSE: Etanercept is a tumour necrosis factor antagonist with
      anti-inflammatory effects. The aim of our study was to evaluate, for the first
      time, the therapeutic efficacy of in vivo inhibition of TNF-alpha in an
      experimental model of periodontitis. EXPERIMENTAL APPROACH: Periodontitis was
      induced in adult male Sprague-Dawley rats by placing a nylon thread ligature
      around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg-1,
      s.c., after placement of the ligature. KEY RESULTS: Periodontitis in rats
      resulted in an inflammatory process characterized by oedema, neutrophil
      infiltration and cytokine production that was followed by the recruitment of
      other inflammatory cells, production of a range of inflammatory mediators, tissue
      damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg-1,
      s.c., after placement of the ligature) significantly reduced the degree of (1)
      periodontitis inflammation and tissue injury (histological score), (2)
      infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of
      nitrotyrosine and cytokines (eg TNF-alpha)) and (4) apoptosis (Bax and Bcl-2
      expression). CONCLUSIONS AND IMPLICATIONS: Taken together, our results clearly
      demonstrate that treatment with etanercept reduces the development of
      inflammation and tissue injury, events associated with periodontitis.

PMID- 17200678
TI  - A multicompartment vascular model for inferring baseline and functional changes
      in cerebral oxygen metabolism and arterial dilation.
AB  - Functional hemodynamic responses are the composite results of underlying
      variations in cerebral oxygen consumption and the dilation of arterial vessels
      after neuronal activity. The development of biophysically based models of the
      cerebral vasculature allows the separation of the neuro-metabolic and neuro
      vascular influences on measurable hemodynamic signals such as functional magnetic
      resonance imaging or optical imaging. We describe a multicompartment model of the
      vascular and oxygen transport dynamics associated with stimulus-driven neuronal
      activation. Our model offers several unique features compared with previous
      formulations such as the ability to estimate baseline blood flow, volume, and
      oxygen consumption from functional data. In addition, we introduce a capillary
      compliance model, arterial and venous oxygen permeability, and model the dynamics
      of extravascular tissue oxygenation. We apply this model to multimodal optical
      spectroscopic and laser speckle imaging of the rat somato-sensory cortex during
      nine conditions of whisker stimulation. By fitting the model using a psuedo
      Bayesian framework to incorporate multimodal observations, we estimate baseline
      blood flow to be 94 (+/-15) mL/100 g min and baseline oxygen consumption to be
      6.7 (+/-1.3) mL O(2)/100 g min. We calculate parametric, linear increases in
      arterial dilation (R(2)=0.96) and CMRO(2) (R(2)=0.87) responses over the nine
      conditions. Other parameters estimated by the model include vascular transit time
      and volume reserve, oxygen content, saturation, diffusivity rate constants, and
      partial pressure of oxygen in the vascular compartments and in the extravascular
      tissue. Finally, we compare this model to earlier work and find that the
      multicompartment model more accurately describes the observed oxygenation changes
      when compared with a single compartment version.

PMID- 17200679
TI  - Stroke induces ependymal cell transformation into radial glia in the
      subventricular zone of the adult rodent brain.
AB  - Adult ependymal cells are postmitotic and highly differentiated. Radial glial
      cells are neurogenic precursors. Here, we show that stroke acutely stimulated
      adult ependymal cell proliferation, and dividing ependymal cells of the lateral
      ventricle had genotype, phenotype, and morphology of radial glial cells in the
      rat. The majority of radial glial cells exhibited symmetrical division about the
      cell cleavage plane, and a radial fiber was maintained throughout each stage of
      cell mitosis. Increases of radial glial cells parallel expansion of neural
      progenitors in the subventricular zone (SVZ). Furthermore, after stroke radial
      glial cells derived from the SVZ supported neuron migration. These results
      indicate that adult ependymal cells divide and transform into radial glial cells
      after stroke, which could function as neural progenitor cells to generate new
      neurons and act as scaffolds to support neuroblast migration towards the ischemic
      boundary region.

PMID- 17200681
TI  - Molecular mechanisms involved in the reciprocal regulation of cyclooxygenase and
      nitric oxide synthase enzymes.
AB  - The nitric oxide (NO) and cyclooxygenase (COX) pathways share a number of
      similarities. NO is the mediator generated from the NO synthase (NOS) pathway and
      COX converts arachidonic acid to prostaglandins (PGs), prostacyclin, and
      thromboxane A2. Two major forms of NOS and COX have been identified to date. The
      constitutive isoforms of these enzymes play an important role in the regulation
      of several physiological states. On the other hand, in an inflammatory setting,
      the inducible isoforms of these enzymes are induced in a variety of cells
      resulting in the production of large amounts NO and PGs, which play pathological
      roles in several disease states. An important link between the NOS and COX
      pathways was made by our group when we demonstrated that NO activates the COX
      enzymes, an event leading to overt production of PGs, suggesting that COX enzymes
      represent important endogenous 'receptor' targets for modulating the multifaceted
      roles of NO. More importantly, mechanistic studies of how NO activates the COX
      enzymes have been undertaken and additional pathways through which NO modulates
      PG production unraveled. The purpose of this article is to cover the advances,
      which have occurred over the years and in particular to summarize experimental
      data that outline how the discovery that NO modulates PG production has impacted
      and extended our understanding of these two systems in physiopathological events.

PMID- 17200680
TI  - Mortality effect of coronary calcification and phosphate binder choice in
      incident hemodialysis patients.
AB  - The risk of death in hemodialysis patients treated with calcium-containing
      phosphate binders or sevelamer is not known. We assessed all-cause mortality in
      127 patients new to hemodialysis assigned to calcium-containing binders or
      sevelamer after a median follow-up of 44 months from randomization. This was a
      predetermined secondary end point of a randomized clinical trial designed to
      assess progression of coronary artery calcium (CAC) scores in the two treatment
      arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects
      randomized to calcium-containing phosphate binders and 11 in subjects randomized
      to sevelamer. Baseline CAC score was a significant predictor of mortality after
      adjustment for age, race, gender, and diabetes with increased mortality
      proportional to baseline score (P=0.002). Mortality was borderline significantly
      lower in subjects randomized to sevelamer (5.3/100 patient years, confidence
      interval (CI) (2.2-8.5) compared to those randomized to calcium-containing
      binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death
      for patients treated with calcium-containing phosphate binders persisted after
      full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In
      subjects new to hemodialysis baseline CAC score was a significant predictor of
      all-cause mortality. Treatment with sevelamer was associated with a significant
      survival benefit as compared to the use of calcium-containing phosphate binders.

PMID- 17200682
TI  - Respiratory syncytial virus nephropathy in rats.
AB  - The pathogenesis of minimal change nephrotic syndrome (MCNS) remains unclear.
      Respiratory tract viruses could contribute to MCNS, and respiratory syncytial
      virus (RSV) is the most common one. In this study, we planned to investigate the
      effects of RSV on the proteinuria and glomerular structure of rats and to explore
      the role of RSV in the pathogenesis of MCNS. Rats were inoculated with 6 x 10(2),
      10(4), and 10(6) PFU (plaque-forming units) RSV and killed on days 4, 8, 14, 28,
      and 60 postinoculation (RSV(4), RSV(8), RSV(14), RSV(28), and RSV(60)). The
      proteinuria and serum parameters were measured; renal histology was observed by
      light microscopy and electron microscopy; immune complex deposits were detected
      by immunofluorescence microscopy; and RSV RNA and RSV titer were determined by in
      situ hybridization and plaque assay, respectively. After inoculation, the
      proteinuria increased, especially in 6 x 10(6) PFU RSV(14),(28). The serum
      albumin of 6 x 10(6) PFU RSV(14),(28) and different-titer RSV(60) decreased.
      Slight hypercellularity in minority glomeruli and swelling in partial tubular
      epithelial cells were observed in RSV(4),(8), whereas a relief of the above
      changes and no abnormalities were detected in RSV(14) and RSV(28),(60),
      respectively, under a light microscope. Extensive foot process effacement was
      observed in 6 x 10(6) PFU RSV(14),(28),(60) under an electron microscope. No
      immune complex deposits were detected in the renal tissues. RSV RNA signal and
      RSV titer of renal tissues, depending on the dose of inoculum, reached their
      climax on day 8 postinoculation. Our study reports for the first time that RSV
      can lead to nephropathy in rats on days 14-60 postinoculation, especially in 6 x
      10(6) PFU RSV-inoculated rats, which may be a new exploration of the pathogenesis
      of MCNS.

PMID- 17200684
TI  - Ethnic differences for developing rheumatic fever in a low-income group living in
      Hawaii.
AB  - The risk factors responsible for acute rheumatic fever (ARF) are complex, in
      part, because group A streptococcus (GAS) infection is a prerequisite for this
      disease. We attempted to differentiate socioeconomic from genetic risk factors by
      studying subjects in a Hawaii pediatric cardiology clinic who qualified for
      Medicaid. This ethnically diverse group was unique because they maintained a low
      socioeconomic but generally healthy lifestyle with more limited risks than those
      living in extremely impoverished conditions. METHODS: Questionnaires were
      administered to consenting subjects in the clinic, who were divided into those
      diagnosed with ARF (n = 26) and those with other (primarily congenital) heart
      diseases (n = 41). RESULTS: The socioeconomic status of the ARF and non-ARF
      groups was lower than that of the Hawaii population in general, and little
      differences were noted between the groups. The ARF group, however, had slightly
      larger household sizes and more children than the non-ARF group. The greatest
      difference was in ethnicity. By the Fisher exact test, the number of Polynesians
      belonging to the ARF group was significantly greater than all other ethnicities
      (P = .005). Polynesians had an odds ratio > 4.80 of developing ARF, which
      increased to 6.33 when number of children per household was considered.
      CONCLUSION: The potential contribution of genetic predisposing factors for
      developing ARF was analyzed in subjects living in a homogeneously low
      socioeconomic level relative to the general Hawaii population. Polynesians were
      at highest risk when compared to other ethnicities living in similar
      socioeconomic conditions.

PMID- 17200685
TI  - Effect of reparation of repeat sequences in the human alpha-synuclein on
      fibrillation ability.
AB  - The aggregation and fibrillation of alpha-synuclein has been implicated as a
      causative factor in the Parkinson's disease. The hexamer motif KTKEGV is found in
      each of the seven imperfect repeat sequences in the N-terminal half of alpha
      synuclein. The motif is not fully conserved in the sixth and seventh repeats. We
      created mutants in which the motif was repaired to be fully conserved in either
      (Rep6 and Rep7) or both (Rep67) of these two repeats. The Rep6 and Rep67 mutants
      showed a greatly reduced propensity to aggregate and fibrillate while all three
      mutants showed greater resistance to HFIP-induced formation of the alpha-helix
      intermediate. Resistance to formation in the partially folded intermediate may
      repress the folding of alpha-synuclein, consequently interfering with the
      aggregation and fibril formation. These results demonstrated that KTKEGV repeats
      may have a significant role in keeping native unfolded status of alpha-synuclein.

PMID- 17200683
TI  - The vascular endothelin system in hypertension--recent patents and discoveries.
AB  - The discovery of endothelin two decades ago has now evolved into an intricate
      vascular endothelin (ET) system. Several ET isoforms, receptors, signaling
      pathways, agonists, antagonists, and clinical applications have been identified
      and documented in first-rate patents. The role of ET as one of the most potent
      endothelium-derived vasoconstricting factors is now complemented by a newly
      discovered role in vascular relaxation. ET synthesis is initiated by the
      transcription of ET genes in endothelial cells and the generation of the gene
      products preproET and big ET, which are further cleaved by specific ET converting
      enzymes into ET-1, -2, -3 and -4 isoforms. ET isoforms bind with different
      affinities to ET(A) and ET(B2) receptors in vascular smooth muscle, and stimulate
      [Ca(2+)](i), protein kinase C, mitogen-activated protein kinase and other
      signaling mechanisms of smooth muscle contraction, growth and proliferation. ET
      also binds to endothelial ET(B1) receptors, which mediate the release of
      vasodilator substances such as nitric oxide, prostacyclin and endothelium-derived
      hyperpolarizing factor. Endothelial ET(B1) receptors may also function in ET re
      uptake and clearance. Although the effects of ET on vascular function and growth
      are well-recognized, the role of ET and its receptors in the regulation of blood
      pressure and in the pathogenesis of hypertension is not clearly established. Salt
      dependent hypertension in experimental animals and some forms of moderate to
      severe hypertension in human may show elevated levels of plasma or vascular ET;
      however, other forms of hypertension show normal ET levels. The currently
      available ET receptor antagonists reduce blood pressure in some forms of
      experimental hypertension. Careful examination of recent patents may identify
      more effective and specific modulators of the vascular ET system for clinical use
      in human hypertension.

PMID- 17200686
TI  - Gamma protocadherin expression in the embryonic chick nervous system.
AB  - Protocadherin gamma (pcdh-gamma) family expression was examined in the embryonic
      chick central nervous system by in situ hybridization. Transcripts were
      visualized in discrete regions of fore-, mid-, and hindbrain at stages 23 and 25
      and in spinal cord and optic lobe at stages 27 and 43, respectively. Results
      suggest that pcdh-gamma may function cooperatively with other cell adhesion
      molecules in neuronal differentiation and establishment of neural networks in
      several areas of the developing brain, particularly regions involved in visual
      processing.

PMID- 17200687
TI  - Increased susceptibility to metabolic alterations in young adult females exposed
      to early malnutrition.
AB  - Early malnutrition during gestation and lactation modifies growth and metabolism
      permanently. Follow up studies using a nutritional rehabilitation protocol have
      reported that early malnourished rats exhibit hyperglycemia and/or
      hyperinsulinemia, suggesting that the effects of early malnutrition are permanent
      and produce a "programming" effect on metabolism. Deleterious effects have mainly
      been observed when early-malnutrition is followed by a high-carbohydrate or a
      high-fat diet. The aim of this study was to evaluate whether following a balanced
      diet subsequent to malnutrition can deter the expression of metabolic disease and
      lead rats to exhibit metabolic responses, similar to those of well-nourished
      controls. Young rats, born from dams malnourished during gestation and lactation
      with a low protein diet, were provided with a regular balanced chow diet upon
      weaning. At 90 days of age, the effects of rehabilitation were determined under
      three different feeding conditions: ad libitum, fasting or fasting-reefed
      satiated.Early-malnourished rats showed an increased rate of body weight gain.
      Males under ad libitum conditions showed an elevated concentration of hepatic
      glycogen and low values of insulin. In the fasting-reefed satiated condition,
      only early-malnourished females showed an alteration in glucose response and
      glucagon level, compared with their well-nourished controls. Data indicate that a
      balanced diet along life after early malnutrition can mask the expression of
      metabolic disorders and that a metabolic challenges due to a prolonged fasting
      and reefed state unmask metabolic deficiencies in early-malnourished females.

PMID- 17200688
TI  - Are heat shock proteins therapeutic target for Parkinson's disease?
AB  - Heat shock proteins (HSPs), known as molecular chaperone to assist protein
      folding, have recently become a research focus in Parkinson's disease (PD)
      because the pathogenesis of this disease is highlighted by the intracellular
      protein misfolding and inclusion body formation. The present review will focus on
      the functions of different HSPs and their protective roles in PD. It is
      postulated that HSPs may serve as protein folding machinery and work together
      with ubiquitin-proteasome system (UPS) to assist in decomposing aberrant
      proteins. Failure of UPS is thought to play a key role in the pathogenesis of PD.
      In addition, HSPs may possess anti-apoptotic effects and keep the homeostasis of
      dopaminergic neurons against stress conditions. The critical role of HSPs and
      recent discovery of some novel HSPs inducers suggest that HSPs may be potential
      therapeutic targets for PD and other neurodegenerative disorders.

PMID- 17200689
TI  - Proteomic identification of 14-3-3zeta as an adapter for IGF-1 and Akt/GSK-3beta
      signaling and survival of renal mesangial cells.
AB  - Recently we demonstrated that IGF-1 expression is increased in the diabetic
      kidney and that it may involve in renal hypertrophy and extracellular matrix
      protein (ECM) accumulation in mesangial cells as seen in diabetic glomerulopathy.
      The present study investigates the molecular mechanism(s) of IGF-1 and
      Akt/glycogen synthase kinase-3beta (GSK-3beta) signaling pathway in the
      regulation of fibronectin and cyclin D1 expression and survival of renal
      mesangial cells. A proteomic approach is also employed to identify protein
      targets of IGF-1 signaling via GSK-3beta inhibition in mesangial cells. We show
      that IGF-1 (100 ng/ml) significantly increases the protein kinase Akt/PKB
      activity (1.5-2-fold, p<0.05) within 1-5 minutes, which is completely blocked by
      the presence of 100 nM Wortmannin (phosphatidyl-inositol 3-kinase inhibitor). Akt
      activation is coupled with Ser9 phosphorylation and inactivation of its down
      stream target GSK-3beta. IGF-1 increases the cyclic AMP-responsive element (CRE)
      binding transcription factor CREB phosphorylation at Ser 133 and CRE-binding
      activity in mesangial cells, which parallels cyclin D1 and fibronectin
      expressions. Both proteins are known to have CRE-sequences in their promoter
      regions upstream of the transcription start site. Suppression of GSK-3beta by
      SB216763 (100 nM) increases CREB phosphorylation, cyclin D1 and fibronectin
      levels. Two dimensional gel electrophoresis followed by MALDI-TOF mass
      spectrometric analysis of mesangial proteins reveals that IGF-1 treatment or an
      inhibition of GSK-3beta increases the expression of the phosphorylated Ser/Thr
      binding signal adapter protein 14-3-3zeta. Immuno-precipitation of 14-3-3zeta
      followed by Western blotting validates the association of phosphorylated GSK
      3beta with 14-3-3zeta in renal mesangial cells. Stable expression of a
      constitutively active GSK-3beta(Ser9Ala) induces cell death while overexpression
      of HA-tagged 14-3-3zeta increases cell viability as measured by MTT assays. These
      results indicate that the Akt/GSK-3beta pathway and the adapter protein 14-3
      3zeta may play an important role in IGF-1 signaling and survival of mesangial
      cells in diabetic nephropathy.

PMID- 17200690
TI  - Intrarenal oxidative stress and augmented angiotensinogen are precedent to renal
      injury in Zucker diabetic fatty rats.
AB  - The Zucker diabetic fatty (ZDF) rat is a model of type II diabetes and metabolic
      syndrome based on impaired glucose tolerance caused by the inherited insulin
      resistance gene. The ZDF rat exhibits progressive nephropathy; however, the
      detailed mechanisms have remained unclear. This study was performed to examine
      the possible involvement of enhanced intrarenal angiotensinogen in the
      development of renal injury in ZDF rats. Genetic pairs of male ZDF rats and
      control lean rats (N=6 each) were maintained from 12 to 17 weeks of age. At 17
      weeks of age, fasting blood glucose and urinary 8-isoprostane levels were
      significantly higher in ZDF rats compared with the controls. Systolic blood
      pressure progressively increased in ZDF rats from 120+/-1 to 137+/-1 mmHg during
      this period. In contrast, systolic blood pressure did not increase in the
      controls. Kidney angiotensinogen protein levels were significantly increased in
      ZDF rats compared with the controls (1.83+/-0.34 vs. 1.00+/-0.17, relative
      ratio). Expression of angiotensin II type 1a receptor mRNA was similar between
      these groups. The measured indices of renal damage in the present study
      (glomerular sclerosis, interstitial expansion, glomerular macrophage
      infiltration, and renal arterial proliferation) were not significantly increased
      at this stage in ZDF rats. However, we previously showed that the increased
      reactive oxygen species-related angiotensinogen enhancement plays an important
      role in the development of renal injury in a genetic salt-sensitive hypertension.
      Thus, the present data suggest that elevated reactive oxygen species and reactive
      oxygen species-associated augmentation of intrarenal angiotensinogen may initiate
      the development of renal injury in ZDF rats.

PMID- 17200691
TI  - Distinct domain-dependent effect of syntaxin1A on amiloride-sensitive sodium
      channel (ENaC) currents in HT-29 colonic epithelial cells.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC), a plasma membrane
      protein mediates sodium reabsorption in epithelial tissues, including the distal
      nephron and colon. Syntaxin1A, a trafficking protein of the t-SNARE family has
      been reported to inhibit ENaC in the Xenopus oocyte expression and artificial
      lipid bilayer systems. The present report describes the regulation of the
      epithelial sodium channel by syntaxin1A in a human cell line that is
      physiologically relevant as it expresses both components and also responds to
      aldosterone stimulation. In order to evaluate the physiological significance of
      syntaxin1A interaction with natively expressed ENaC, we over-expressed HT-29 with
      syntaxin1A constructs comprising various motifs. Unexpectedly, we observed the
      augmentation of amiloride-sensitive currents with wild-type syntaxin1A full
      length construct (1-288) in this cell line. Both gammaENaC and neutralizing
      syntaxin1A antibodies blocked native expression as amiloride-sensitive sodium
      currents were inhibited while munc18-1 antibody reversed this effect. The coiled
      coiled domain H3 (194-266) of syntaxin1A inhibited, however the inclusion of the
      transmembrane domain to this motif (194-288) augmented amiloride sensitive
      currents. More so, data suggest that ENaC interacts with multiple syntaxin1A
      domains, which differentially regulate channel function. This functional
      modulation is the consequence of the physical enhancement of ENaC at the cell
      surface in cells over-expressed with syntaxin(s). Our data further suggest that
      syntaxin1A up-regulates ENaC function by multiple mechanisms that include PKA,
      PLC, PI3 and MAP Kinase (p42/44) signaling systems. We propose that syntaxin1A
      possesses distinct inhibitory and stimulatory domains that interact with ENaC
      subunits, which critically determines the overall ENaC functionality/regulation
      under distinct physiological conditions.

PMID- 17200694
TI  - Half a century of medical history.

PMID- 17200693
TI  - Urokinase separation from cell culture broth of a human kidney cell line.
AB  - A single step ion-exchange chromatography on a sulfo-propyl (SP)- Sepharose
      column was performed to separate both the high molecular weight (HMW)- and low
      molecular weight (LMW)- forms of enzymatically active urokinase type plasminogen
      activator from human kidney (HT1080) cell culture media. The level of urokinase
      secreted by the cell line reached to about 145 Plough units/ml culture broth
      within 48 h of cultivation. The conditioned cell culture media was applied
      directly to the column without any prior concentration steps. Polyacrylamide gel
      electrophoresis of the column eluates in the presence of sodium dodecyl sulphate
      showed that the cell line secretes three forms of two-chain high molecular weight
      (HMW) urokinase of molecular weights (M(r)) 64,000, 60,900 and 55,000. In
      addition, two low molecular weight (LMW) forms of M(r) 22,000 and 20,000;
      proteolytic cleavage products of HMW, were also found. The HMW and LMW forms had
      intrinsic plasminogen dependent proteolytic activity as judged by zymographic
      analysis. The specific activity of the pooled peak fractions increased
      (approximately 93-fold) to values as high as 1481 Plough units/ mg protein. Both
      HMW as well as LMW forms were obtained in significantly high yields.

PMID- 17200692
TI  - Prion-derived copper-binding peptide fragments catalyze the generation of
      superoxide anion in the presence of aromatic monoamines.
AB  - OBJECTIVES: Studies have proposed two opposing roles for copper-bound forms of
      prion protein (PrP) as an anti-oxidant supporting the neuronal functions and as a
      pro-oxidant leading to neurodegenerative process involving the generation of
      reactive oxygen species. The aim of this study is to test the hypothesis in which
      putative copper-binding peptides derived from PrP function as possible catalysts
      for monoamine-dependent conversion of hydrogen peroxide to superoxide in vitro.
      MATERIALS AND METHODS: Four peptides corresponding to the copper (II)-binding
      motifs in PrP were synthesized and used for analysis of peptide-catalyzed
      generation of superoxide in the presence of Cu (II) and other factors naturally
      present in the neuronal tissues. RESULTS: Among the Cu-binding peptides tested,
      the amino acid sequence corresponding to the Cu-binding site in the helical
      region was shown to be the most active for superoxide generation in the presence
      of Cu(II), hydrogen peroxide and aromatic monoamines, known precursors or
      intermediates of neurotransmitters. Among monoamines tested, three compounds
      namely phenylethylamine, tyramine and benzylamine were shown to be good
      substrates for superoxide-generating reactions by the Cu-bound helical peptide.
      CONCLUSIONS: Possible roles for these reactions in development of prion disease
      were suggested.

PMID- 17200695
TI  - The practice of practical education: male students and female apprentices in the
      Lying-in Hospital of Gottingen University, 1792-1815.

PMID- 17200696
TI  - Medicine, race and the general good: the career of Thomas N G Te Water (1857
      1926), South African doctor and medical politician.

PMID- 17200697
TI  - Institutional care for the mentally defective, 1914-1948: diversity as a response
      to individual needs and an indication of lack of policy coherence.

PMID- 17200698
TI  - Deeds and words in the suffrage military hospital in Endell Street.

PMID- 17200699
TI  - Problematizations and path dependency: HIV/AIDS policies in Denmark and Sweden.

PMID- 17200700
TI  - Physician-scientist, heal thyself . . .
AB  - Historically, physician-scientists have had dual roles in caring for patients and
      in performing investigative research that could potentially lead to new
      diagnostics and therapeutics. Physician-scientists conducted teaching rounds in
      the hospital, surrounded by eager house staff and medical students, and were
      often avidly pursued as the most important sources of new knowledge for trainees.
      But alas, times have changed. Now physician-scientists are rarely seen in the
      hospital; they are most often spotted at their desks tapping out yet another
      grant application. Most struggle to find the time to mentor students and clinical
      trainees, let alone to care for patients in the hospital, even though these
      interactions are often the motivating forces for scientific creativity.

PMID- 17200701
TI  - Tales from the crypts: regulatory peptides and cytokines in gastrointestinal
      homeostasis and disease.
AB  - The gastrointestinal (GI) tract is composed of a diverse set of organs that
      together receive extracorporeal nutrition and convert it to energy substrates and
      cellular building blocks. In the process, it must sort through all that we ingest
      and discriminate what is useable from what is not, and having done that, it
      discards what is "junk." To accomplish these many and varied tasks, the GI tract
      relies on endogenous enteric hormones produced by enteroendocrine cells and the
      enteric nervous system. In many instances, the mediators of these tasks are small
      peptides that home to the CNS and accessory gut organs to coordinate oral intake
      with digestive secretions. As the contents of ingested material can contain
      harmful agents, the gut is armed with an extensive immune system. A breach of the
      epithelial barrier of the GI tract can result in local and eventually systemic
      disease if the gut does not mount an aggressive immune response.

PMID- 17200702
TI  - Gastrointestinal regulation of food intake.
AB  - Despite substantial fluctuations in daily food intake, animals maintain a
      remarkably stable body weight, because overall caloric ingestion and expenditure
      are exquisitely matched over long periods of time, through the process of energy
      homeostasis. The brain receives hormonal, neural, and metabolic signals
      pertaining to body-energy status and, in response to these inputs, coordinates
      adaptive alterations of energy intake and expenditure. To regulate food
      consumption, the brain must modulate appetite, and the core of appetite
      regulation lies in the gut-brain axis. This Review summarizes current knowledge
      regarding the neuroendocrine regulation of food intake by the gastrointestinal
      system, focusing on gastric distention, intestinal and pancreatic satiation
      peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms
      governing nutrient sensing and peptide secretion by enteroendocrine cells,
      including novel taste-like pathways. The increasingly nuanced understanding of
      the mechanisms mediating gut-peptide regulation and action provides promising
      targets for new strategies to combat obesity and diabetes.

PMID- 17200703
TI  - The role of gut hormones in glucose homeostasis.
AB  - The gastrointestinal tract has a crucial role in the control of energy
      homeostasis through its role in the digestion, absorption, and assimilation of
      ingested nutrients. Furthermore, signals from the gastrointestinal tract are
      important regulators of gut motility and satiety, both of which have implications
      for the long-term control of body weight. Among the specialized cell types in the
      gastrointestinal mucosa, enteroendocrine cells have important roles in regulating
      energy intake and glucose homeostasis through their actions on peripheral target
      organs, including the endocrine pancreas. This article reviews the biological
      actions of gut hormones regulating glucose homeostasis, with an emphasis on
      mechanisms of action and the emerging therapeutic roles of gut hormones for the
      treatment of type 2 diabetes mellitus.

PMID- 17200704
TI  - Corticotropin-releasing factor receptors and stress-related alterations of gut
      motor function.
AB  - Over the past few decades, corticotropin-releasing factor (CRF) signaling
      pathways have been shown to be the main coordinators of the endocrine,
      behavioral, and immune responses to stress. Emerging evidence also links the
      activation of CRF receptors type 1 and type 2 with stress-related alterations of
      gut motor function. Here, we review the role of CRF receptors in both the brain
      and the gut as part of key mechanisms through which various stressors impact
      propulsive activity of the gastrointestinal system. We also examine how these
      mechanisms translate into the development of new approaches for irritable bowel
      syndrome, a multifactorial disorder for which stress has been implicated in the
      pathophysiology.

PMID- 17200705
TI  - Celiac disease: pathogenesis of a model immunogenetic disease.
AB  - Celiac disease is characterized by small-intestinal mucosal injury and nutrient
      malabsorption in genetically susceptible individuals in response to the dietary
      ingestion of wheat gluten and similar proteins in barley and rye. Disease
      pathogenesis involves interactions among environmental, genetic, and
      immunological factors. Although celiac disease is predicted by screening studies
      to affect approximately 1% of the population of the United States and is seen
      both in children and in adults, 10%-15% or fewer of these individuals have been
      diagnosed and treated. This article focuses on the role of adaptive and innate
      immune mechanisms in the pathogenesis of celiac disease and how current concepts
      of immunopathogenesis might provide alternative approaches for treating celiac
      disease.

PMID- 17200706
TI  - The pancreatic stellate cell: a star on the rise in pancreatic diseases.
AB  - Pancreatic stellate cells (PaSCs) are myofibroblast-like cells found in the areas
      of the pancreas that have exocrine function. PaSCs are regulated by autocrine and
      paracrine stimuli and share many features with their hepatic counterparts,
      studies of which have helped further our understanding of PaSC biology.
      Activation of PaSCs induces them to proliferate, to migrate to sites of tissue
      damage, to contract and possibly phagocytose, and to synthesize ECM components to
      promote tissue repair. Sustained activation of PaSCs has an increasingly
      appreciated role in the fibrosis that is associated with chronic pancreatitis and
      with pancreatic cancer. Therefore, understanding the biology of PaSCs offers
      potential therapeutic targets for the treatment and prevention of these diseases.

PMID- 17200709
TI  - A dominant role for glucose in beta cell compensation of insulin resistance.
AB  - Increased insulin secretion and expansion of pancreatic beta cell mass work
      together to maintain normal glucose levels when insulin resistance develops.
      Changes in glucose concentration have long been known to have profound effects
      upon the rates of insulin secretion and beta cell mass, but various other agents
      can also cause changes, raising questions about which mechanisms are dominant.
      Evidence favoring a dominant role for glucose is provided by Terauchi et al. in
      this issue of the JCI (see the related article beginning on page 246). Mice
      haploinsufficient for beta cell glucokinase (Gck) were unable to increase their
      beta cell mass in response to insulin resistance produced by high-fat feeding.
      Gck is known to be the glucose sensor for glucose metabolism in beta cells. The
      study also provides strong evidence that insulin receptor substrate 2 (Irs2),
      which is known to have major effects on beta cell growth and survival, is a key
      downstream mediator of the effects of glucose found in this study.

PMID- 17200707
TI  - Inflammation, atrophy, and gastric cancer.
AB  - The association between chronic inflammation and cancer is now well established.
      This association has recently received renewed interest with the recognition that
      microbial pathogens can be responsible for the chronic inflammation observed in
      many cancers, particularly those originating in the gastrointestinal system. A
      prime example is Helicobacter pylori, which infects 50% of the world's population
      and is now known to be responsible for inducing chronic gastric inflammation that
      progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review
      provides an overview of recent progress in elucidating the bacterial properties
      responsible for colonization of the stomach, persistence in the stomach, and
      triggering of inflammation, as well as the host factors that have a role in
      determining whether gastritis progresses to gastric cancer. We also discuss how
      the increased understanding of the relationship between inflammation and gastric
      cancer still leaves many questions unanswered regarding recommendations for
      prevention and treatment.

PMID- 17200710
TI  - Prostaglandin-secreting cells: a portable first aid kit for tissue repair.
AB  - After intestinal injury, both the number and type of intestinal epithelial cells
      must be restored. Intestinal stem cells, located at the base of the intestinal
      crypt, repopulate the depleted crypt in a process known as compensatory
      proliferation. In this issue of the JCI, Brown et al. describe a new mechanism by
      which this process is regulated (see the related article beginning on page 258).
      Surprisingly, they find that a subset of stromal cells present within the
      intestinal tissue and expressing the proliferative factor prostaglandin
      endoperoxidase synthase 2 (Ptgs2) is repositioned next to the intestinal stem
      cell compartment where local production of PGE(2) controls injury-induced
      epithelial cell proliferation.

PMID- 17200708
TI  - Menetrier disease and gastrointestinal stromal tumors: hyperproliferative
      disorders of the stomach.
AB  - Menetrier disease and gastrointestinal stromal tumors (GISTs) are
      hyperproliferative disorders of the stomach caused by dysregulated receptor
      tyrosine kinases (RTKs). In Menetrier disease, overexpression of TGF-alpha, a
      ligand for the RTK EGFR, results in selective expansion of surface mucous cells
      in the body and fundus of the stomach. In GISTs, somatic mutations of the genes
      encoding the RTK KIT (or PDGFRA in a minority of cases) result in constitutive
      kinase activity and neoplastic transformation of gut pacemaker cells
      (interstitial cells of Cajal). On the basis of the involvement of these RTKs in
      the pathogenesis of these disorders, Menetrier disease patients have been
      effectively treated with a blocking monoclonal antibody specific for EGFR and
      GIST patients with KIT and PDGFRA tyrosine kinase inhibitors.

PMID- 17200711
TI  - Beta blocker specificity: a building block toward personalized medicine.
AB  - Drugs known as beta blockers, which antagonize the beta-adrenergic receptor (beta
      AR), are an important component of the treatment regimen for chronic heart
      failure (HF). However, a significant body of evidence indicates that genetic
      heterogeneity at the level of the beta(1)-AR may be a factor in explaining the
      variable responses of HF patients to beta blockade. In this issue of the JCI,
      Rochais et al. describe how a single amino acid change in beta(1)-AR alters its
      structural conformation and improves its functional response to carvedilol, a
      beta blocker currently used in the treatment of HF (see the related article
      beginning on page 229). This may explain why some HF patients have better
      responses not only to carvedilol but to certain other beta blockers as well. The
      data greatly enhance our mechanistic understanding of myocardial adrenergic
      signaling and support the development of "tailored" or "personalized" medicine,
      in which specific therapies could be prescribed based on a patient's genotype.

PMID- 17200712
TI  - Macrophage heterogeneity and tissue lipids.
AB  - Macrophages are present as resident cells in adipose tissue, and blood monocytes
      are recruited in increased numbers to sites of lipid accumulation in
      atherosclerosis, a modified form of inflammation in the arterial wall. Recent
      findings reported by 3 separate groups in this issue of the JCI provide evidence
      for distinct monocyte subsets, differential chemokine receptor usage, and
      phenotypic modulation of macrophages in murine models of genetic and high-fat
      diet-induced disease (see the related articles beginning on pages 175, 185, and
      195). These studies raise prospects for selective therapeutic targets to
      ameliorate macrophage hyperinflammatory responses, while sparing host defense and
      repair mechanisms.

PMID- 17200713
TI  - Atherogenic remnant lipoproteins: role for proteoglycans in trapping,
      transferring, and internalizing.
AB  - Unraveling the mechanisms controlling remnant lipoprotein clearance is important,
      as these lipoproteins are highly atherogenic. The most critical molecule in this
      process is apoE, which mediates high-affinity binding of remnant lipoproteins to
      members of the LDL receptor (LDLR) family and cell-surface heparan sulfate
      proteoglycans (HSPGs), which have been shown to play major independent as well as
      cooperative roles in remnant lipoprotein clearance. While all the players may
      have been identified, our understanding of how they interact and function
      together continues to evolve. In this issue of the JCI, MacArthur et al. (see the
      related article beginning on page 153) demonstrated that HSPGs under normal
      physiological conditions are critically important in the clearance of remnant
      lipoproteins, independent of LDLR family members. The complexity of VLDL and
      chylomicron remnant clearance was exemplified by the studies of Jones et al.,
      also in this issue (see the related article beginning on page 165). Despite
      defective clearance of LDL in mice with a deficiency in the adaptor protein
      controlling internalization of the LDLR, called autosomal recessive
      hypercholesterolemia (ARH), remnant lipoprotein clearance was not grossly
      abnormal. A likely explanation is that the abnormal LDLRs bind the remnants and
      then transfer them to another acceptor for internalization. While the studies
      clearly demonstrate that the LDLR-related protein 1 is not involved and suggest a
      role for an additional unidentified receptor, it remains a possibility that HSPGs
      are responsible for remnant uptake by hepatocytes in the presence of defective
      LDLR internalization.

PMID- 17200714
TI  - Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining
      sensitivity to BCL2 antagonist ABT-737.
AB  - Antiapoptotic B cell leukemia/lymphoma 2 (BCL2) family proteins are expressed in
      many cancers, but the circumstances under which these proteins are necessary for
      tumor maintenance are poorly understood. We exploited a novel functional assay
      that uses BCL2 homology domain 3 (BH3) peptides to predict dependence on
      antiapoptotic proteins, a strategy we call BH3 profiling. BH3 profiling
      accurately predicts sensitivity to BCL2 antagonist ABT-737 in primary chronic
      lymphocytic leukemia (CLL) cells. BH3 profiling also accurately distinguishes
      myeloid cell leukemia sequence 1 (MCL1) from BCL2 dependence in myeloma cell
      lines. We show that the special sensitivity of CLL cells to BCL2 antagonism
      arises from the requirement that BCL2 tonically sequester proapoptotic BIM in
      CLL. ABT-737 displaced BIM from BCL2's BH3-binding pocket, allowing BIM to
      activate BAX, induce mitochondrial permeabilization, and rapidly commit the CLL
      cell to death. Our experiments demonstrate that BCL2 expression alone does not
      dictate sensitivity to ABT-737. Instead, BCL2 complexed to BIM is the critical
      target for ABT-737 in CLL. An important implication is that in cancer, BCL2 may
      not effectively buffer chemotherapy death signals if it is already sequestering
      proapoptotic BH3-only proteins. Indeed, activator BH3-only occupation of BCL2 may
      prime cancer cells for death, offering a potential explanation for the marked
      chemosensitivity of certain cancers that express abundant BCL2, such as CLL and
      follicular lymphoma.

PMID- 17200715
TI  - Liver heparan sulfate proteoglycans mediate clearance of triglyceride-rich
      lipoproteins independently of LDL receptor family members.
AB  - We examined the role of hepatic heparan sulfate in triglyceride-rich lipoprotein
      metabolism by inactivating the biosynthetic gene GlcNAc N-deacetylase/N
      sulfotransferase 1 (Ndst1) in hepatocytes using the Cre-loxP system, which
      resulted in an approximately 50% reduction in sulfation of liver heparan sulfate.
      Mice were viable and healthy, but they accumulated triglyceride-rich lipoprotein
      particles containing apoB-100, apoB-48, apoE, and apoCI-IV. Compounding the
      mutation with LDL receptor deficiency caused enhanced accumulation of both
      cholesterol- and triglyceride-rich particles compared with mice lacking only LDL
      receptors, suggesting that heparan sulfate participates in the clearance of
      cholesterol-rich lipoproteins as well. Mutant mice synthesized VLDL normally but
      showed reduced plasma clearance of human VLDL and a corresponding reduction in
      hepatic VLDL uptake. Retinyl ester excursion studies revealed that clearance of
      intestinally derived lipoproteins also depended on hepatocyte heparan sulfate.
      These findings show that under normal physiological conditions, hepatic heparan
      sulfate proteoglycans play a crucial role in the clearance of both intestinally
      derived and hepatic lipoprotein particles.

PMID- 17200716
TI  - Disruption of LDL but not VLDL clearance in autosomal recessive
      hypercholesterolemia.
AB  - Genetic defects in LDL clearance result in severe hypercholesterolemia and
      premature atherosclerosis. Mutations in the LDL receptor (LDLR) cause familial
      hypercholesterolemia (FH), the most severe form of genetic hypercholesterolemia.
      A phenocopy of FH, autosomal recessive hypercholesterolemia (ARH), is due to
      mutations in an adaptor protein involved in LDLR internalization. Despite
      comparable reductions in LDL clearance rates, plasma LDL levels are substantially
      lower in ARH than in FH. To determine the metabolic basis for this difference, we
      examined the synthesis and catabolism of VLDL in murine models of FH (Ldlr(-/-))
      and ARH (Arh(-/-)). The hyperlipidemic response to a high-sucrose diet was
      greatly attenuated in Arh(-/-) mice compared with Ldlr(-/-) mice despite similar
      rates of VLDL secretion. The rate of VLDL clearance was significantly higher in
      Arh(-/-) mice than in Ldlr(-/-) mice, suggesting that LDLR-dependent uptake of
      VLDL is maintained in the absence of ARH. Consistent with these findings,
      hepatocytes from Arh(-/-) mice (but not Ldlr(-/-) mice) internalized beta
      migrating VLDL (beta-VLDL). These results demonstrate that ARH is not required
      for LDLR-dependent uptake of VLDL by the liver. The preservation of VLDL remnant
      clearance attenuates the phenotype of ARH and likely contributes to greater
      responsiveness to statins in ARH compared with FH.

PMID- 17200717
TI  - Obesity induces a phenotypic switch in adipose tissue macrophage polarization.
AB  - Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and
      contribute to insulin resistance. We hypothesized that macrophages migrating to
      adipose tissue upon high-fat feeding may differ from those that reside there
      under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+)
      population of ATMs in adipose tissue of obese mice that was not seen in lean
      mice. ATMs from lean mice expressed many genes characteristic of M2 or
      "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet
      induced obesity decreased expression of these genes in ATMs while increasing
      expression of genes such as those encoding TNF-alpha and iNOS that are
      characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs
      from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at
      levels similar to those from lean mice. The antiinflammatory cytokine IL-10,
      which was overexpressed in ATMs from lean mice, protected adipocytes from TNF
      alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in
      the activation state of ATMs from an M2-polarized state in lean animals that may
      protect adipocytes from inflammation to an M1 proinflammatory state that
      contributes to insulin resistance.

PMID- 17200718
TI  - Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate
      within atherosclerotic plaques.
AB  - Monocytes participate critically in atherosclerosis. There are 2 major subsets
      expressing different chemokine receptor patterns: CCR2(+)CX3CR1(+)Ly-6C(hi) and
      CCR2(-)CX3CR1(++)Ly-6C(lo) monocytes. Both C-C motif chemokine receptor 2 (CCR2)
      and C-X(3)-C motif chemokine receptor 1 (CX3CR1) are linked to progression of
      atherosclerotic plaques. Here, we analyzed mouse monocyte subsets in apoE
      deficient mice and traced their differentiation and chemokine receptor usage as
      they accumulated within atherosclerotic plaques. Blood monocyte counts were
      elevated in apoE(-/-) mice and skewed toward an increased frequency of CCR2(+)Ly
      6C(hi) monocytes in apoE(-/-) mice fed a high-fat diet. CCR2(+)Ly-6C(hi)
      monocytes efficiently accumulated in plaques, whereas CCR2(-)Ly-6C(lo) monocytes
      entered less frequently but were more prone to developing into plaque cells
      expressing the dendritic cell-associated marker CD11c, indicating that phagocyte
      heterogeneity in plaques is linked to distinct types of entering monocytes. CCR2(
      ) monocytes did not rely on CX3CR1 to enter plaques. Instead, they were partially
      dependent upon CCR5, which they selectively upregulated in apoE(-/-) mice. By
      comparison, CCR2(+)Ly-6C(hi) monocytes unexpectedly required CX3CR1 in addition
      to CCR2 and CCR5 to accumulate within plaques. In many other inflammatory
      settings, these monocytes utilize CCR2, but not CX3CR1, for trafficking. Thus,
      antagonizing CX3CR1 may be effective therapeutically in ameliorating CCR2(+)
      monocyte recruitment to plaques without impairing their CCR2-dependent responses
      to inflammation overall.

PMID- 17200719
TI  - Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give
      rise to macrophages in atheromata.
AB  - Macrophage accumulation participates decisively in the development and
      exacerbation of atherosclerosis. Circulating monocytes, the precursors of
      macrophages, display heterogeneity in mice and humans, but their relative
      contribution to atherogenesis remains unknown. We report here that the Ly-6C(hi)
      monocyte subset increased dramatically in hypercholesterolemic apoE-deficient
      mice consuming a high-fat diet, with the number of Ly-6C(hi) cells doubling in
      the blood every month. Ly-6C(hi) monocytes adhered to activated endothelium,
      infiltrated lesions, and became lesional macrophages. Hypercholesterolemia
      associated monocytosis (HAM) developed from increased survival, continued cell
      proliferation, and impaired Ly-6C(hi) to Ly-6C(lo) conversion and subsided upon
      statin-induced cholesterol reduction. Conversely, the number of Ly-6C(lo) cells
      remained unaffected. Thus, we believe that Ly-6C(hi) monocytes represent a newly
      recognized component of the inflammatory response in experimental
      atherosclerosis.

PMID- 17200720
TI  - Real-time optical recording of beta1-adrenergic receptor activation reveals
      supersensitivity of the Arg389 variant to carvedilol.
AB  - Antagonists of beta-adrenergic receptors (beta-ARs) have become a main
      therapeutic regimen for the treatment of heart failure even though the mechanisms
      of their beneficial effects are still poorly understood. Here, we used
      fluorescent resonance energy transfer-based (FRET-based) approaches to directly
      monitor activation of the beta(1)-AR and downstream signaling. While the commonly
      used beta-AR antagonists metoprolol, bisoprolol, and carvedilol displayed varying
      degrees of inverse agonism on the Gly389 variant of the receptor (i.e., actively
      switching off the beta(1)-AR), surprisingly, only carvedilol showed very specific
      and marked inverse agonist effects on the more frequent Arg389 variant. These
      specific effects of carvedilol on the Arg389 variant of the beta(1)-AR were also
      seen for control of beating frequency in rat cardiac myocytes expressing the 2
      receptor variants. This FRET sensor permitted direct observation of activation of
      the beta(1)-AR in living cells in real time. It revealed that beta(1)-AR variants
      dramatically differ in their responses to diverse beta blockers, with possible
      consequences for their clinical use.

PMID- 17200723
TI  - The US's changing competitiveness in the biomedical sciences.

PMID- 17200721
TI  - Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in
      response to high-fat diet-induced insulin resistance.
AB  - Glucokinase (Gck) functions as a glucose sensor for insulin secretion, and in
      mice fed standard chow, haploinsufficiency of beta cell-specific Gck (Gck(+/-))
      causes impaired insulin secretion to glucose, although the animals have a normal
      beta cell mass. When fed a high-fat (HF) diet, wild-type mice showed marked beta
      cell hyperplasia, whereas Gck(+/-) mice demonstrated decreased beta cell
      replication and insufficient beta cell hyperplasia despite showing a similar
      degree of insulin resistance. DNA chip analysis revealed decreased insulin
      receptor substrate 2 (Irs2) expression in HF diet-fed Gck(+/-) mouse islets
      compared with wild-type islets. Western blot analyses confirmed upregulated Irs2
      expression in the islets of HF diet-fed wild-type mice compared with those fed
      standard chow and reduced expression in HF diet-fed Gck(+/-) mice compared with
      those of HF diet-fed wild-type mice. HF diet-fed Irs2(+/-) mice failed to show a
      sufficient increase in beta cell mass, and overexpression of Irs2 in beta cells
      of HF diet-fed Gck(+/-) mice partially prevented diabetes by increasing beta cell
      mass. These results suggest that Gck and Irs2 are critical requirements for beta
      cell hyperplasia to occur in response to HF diet-induced insulin resistance.

PMID- 17200722
TI  - Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic
      epithelial proliferation during injury.
AB  - We identified cellular and molecular mechanisms within the stem cell niche that
      control the activity of colonic epithelial progenitors (ColEPs) during injury.
      Here, we show that while WT mice maintained ColEP proliferation in the rectum
      following injury with dextran sodium sulfate, similarly treated Myd88(-/-) (TLR
      signaling-deficient) and prostaglandin-endoperoxide synthase 2(-/-) (Ptgs2(-/-))
      mice exhibited a profound inhibition of epithelial proliferation and cellular
      organization within rectal crypts. Exogenous addition of 16,16-dimethyl PGE(2)
      (dmPGE(2)) rescued the effects of this injury in both knockout mouse strains,
      indicating that Myd88 signaling is upstream of Ptgs2 and PGE(2). In WT and Myd88(
      /-) mice, Ptgs2 was expressed in scattered mesenchymal cells. Surprisingly, Ptgs2
      expression was not regulated by injury. Rather, in WT mice, the combination of
      injury and Myd88 signaling led to the repositioning of a subset of the Ptgs2
      expressing stromal cells from the mesenchyme surrounding the middle and upper
      crypts to an area surrounding the crypt base adjacent to ColEPs. These findings
      demonstrate that Myd88 and prostaglandin signaling pathways interact to preserve
      epithelial proliferation during injury using what we believe to be a previously
      undescribed mechanism requiring proper cellular mobilization within the crypt
      niche.

PMID- 17200724
TI  - Comparison of capillary zone electrophoresis and isotachophoresis determination
      of dimethindene enantiomers in pharmaceuticals using charged carboxyethyl-beta
      cyclodextrin as a chiral selector.
AB  - Charged cyclodextrin-mediated capillary electrophoretic methods (capillary zone
      electrophoresis [CZE] and isotachophoresis [ITP]) in a hydrodynamically closed
      separation system with suppressed electroosmotic flow and UV absorbance
      photometric detection (for CZE) or conductivity detection (for ITP) were
      developed for a highly effective separation and quantitation of dimethindene
      enantiomers in various pharmaceutical formulations (solution, gel, capsules).
      Optimized electrolyte systems were based on low-mobility buffer constituents
      (epsilon-aminocaproic acid, beta-alanine, potassium acetate, acetic acid),
      negatively charged (at pH > 4.5) carboxyethyl-beta-cyclodextrin (CE-beta-CD),
      serving as chiral selector, and methylhydroxyethylcellulose, serving as an
      electroosmotic flow suppressor. Complete enantioseparations of dimethindene in
      the presence of low concentrations of CE-beta-CD (2.5 mg/ml in CZE, 6.0 mg/ml in
      ITP) clearly indicated a role of charge of this chiral selector in
      enantioresolution. It also outlined the potential of charged CD-derivatives as
      chiral selectors for various CE techniques. The proposed methods were
      successfully validated, appraising parameters of sensitivity, linearity,
      precision, accuracy/recovery, and robustness, and then, they were applied to
      pharmaceutical samples. Consistent results obtained by both CE methods indicate
      their usefulness for routine use.

PMID- 17200725
TI  - Effects of (+)SKF 10047, a sigma-1 selective agonist, on isolation-induced
      aggression in male mice.
AB  - sigma-1 Receptors have been identified in numerous brain regions, including areas
      such as hypothalamus and amygdala, which have long been linked to the regulation
      of aggression. However, there is no clear information with respect to the
      possible effects of sigma-1 ligands on aggressive behavior in laboratory animals.
      Consequently, the present study examined the effects of (+)SKF 10047 (0.5-6
      mg/kg, i.p.), a sigma-1 prototypical agonist, on isolation-induced aggression in
      male mice, using an ethopharmacological approach. Individually housed mice were
      exposed to anosmic "standard opponents" 30 min after drug administration. Ten
      minutes of diadic interactions were staged between a singly housed and an anosmic
      mouse in a neutral area. The encounters were videotaped, and the accumulated time
      allocated by subjects to 10 broad behavioral categories was estimated using an
      ethologically based analysis. Results showed that (+)SKF 10047 (6 mg/kg) produced
      a significant reduction of offensive behaviors, without affecting immobility.
      Social investigation behaviors were also slightly increased after drug treatment
      (2-6 mg/kg). These results suggest a role for sigma-1 receptors in aggression
      modulation in mice.

PMID- 17200726
TI  - Effect of blood transfusion on gene expression of transforming growth factor beta
      1 and the alpha subunit of interleukin-2 receptor in a model of colonic wound
      healing.
AB  - Blood transfusions have been shown in the past to compromise wound healing in
      experimental models of colonic anastomosis. Transforming growth factor beta
      (TGFbeta) has been proposed to play a major role in the process of colonic wound
      healing, and its expression is believed to be modulated by interleukin-2 (IL2).
      According to an earlier report, the postoperative administration of the histamine
      receptor-2 antagonist ranitidine increases the blood levels of soluble IL2
      receptor in humans undergoing abdominal surgery and could thus affect molecular
      determinants of colonic anastomosis. In this study we examined the effect of
      blood transfusions, with and without ranitidine administration, on the gene
      expression of TGFbeta(1) and the specificity-conveying alpha subunit of the
      receptor for IL2, in rat perianastomotic tissue. Analysis of gene expression by
      semiquantitative RT-PCR revealed a tendency for downregulation of both genes,
      albeit in a statistically nonsignificant manner. This effect was not prevented by
      the postoperative administration of ranitidine. On the other hand, there appears
      to be a significant correlation between expression of TGFbeta(1) and that of IL2
      receptor alpha subunit, irrespective of treatment.

PMID- 17200727
TI  - Effect of fructose-rich high-fat diet on glucose sensitivity and atherosclerosis
      in nonhuman primate.
AB  - The present study examined a new model of impaired glucose tolerance (IGT) in a
      nonhuman primate fed with a high-fructose and high-fat (HFF) diet that contained
      15% lard, 31% fructose, and 1% cholesterol. Female cynomolgus monkeys (age, 3-4
      years) were divided into two groups: 1) those fed with normal control diet (N =
      5) and 2) those fed with HFF diet (N = 5). In the HFF diet group, total
      cholesterol and low-density lipoprotein cholesterol in blood were significantly
      increased four- to fivefold when compared with the normal control diet group. No
      difference in the blood glucose, insulin, hemoglobin A1c, and triglyceride levels
      was detected between the two groups. Plasma levels of adiponectin, but not of
      resistin, were significantly higher in HFF diet at 20 weeks after HFF diet
      feeding. Oral glucose tolerance test was performed before HFF diet feeding and at
      12 and 24 weeks after HFF diet feeding, but no significant changes in glucose
      sensitivity were observed even 24 weeks after HFF diet feeding. Twenty-four weeks
      after HFF diet feeding, accumulated foam cells and infiltrated macrophages were
      histologically detected in the thoracic aorta, in addition to a fatty liver.
      Interestingly, the pancreatic beta cells appeared normal in the HFF diet group.
      These results show that a chronic HFF diet does not induce IGT but can cause
      atherosclerotic lesions in conjunction with the generation of a fatty liver
      phenotype in cynomolgus monkey; however, the present results are very preliminary
      and they need to be validated in larger-scale studies in the future.

PMID- 17200728
TI  - Effects of chemotherapy and/or radiotherapy on survivin expression in ovarian
      cancer.
AB  - Survivin, a member of apoptosis protein inhibitor family, is upregulated in
      various malignancies, especially in chemotherapy- and/or radiation-resistant cell
      lines. In this study, the correlation between the level of survivin expression
      and degree of apoptosis was investigated in three ovarian cancer lines (two
      chemoresistant cell lines SKOV-3 and OVCAR-3, as well as one chemosensitive cell
      line OV2008) treated with 5 microg/ml of cisdiamminedichloroplatinum (cisplatin,
      CDDP) for 24 h, 2 Gy of (60)Co irradiation, or 5 microg/ml CDDP for 3 h plus 2 Gy
      of (60)Co, respectively. We also evaluated the survivin mRNA abundance in
      patients with advanced ovarian cancers during CDDP treatment. In the ovarian
      cancer cell lines, survivin mRNA abundance and protein contents were
      significantly increased after the treatments while the apoptotic rates did not
      change in SKOV-3 and OVCAR-3. Moreover, in OVA2008 cells the expression of
      survivin decreased and the apoptotic rate significantly increased after CDDP and
      combined treatments. Survivin mRNA was not detectable in normal ovarian tissues
      and benign ovarian tumors. However, it was observed in the resected tumor
      specimens from 20 patients with advanced ovarian cancer. These results suggested
      that survivin may play an important role in the resistance to chemotherapy and
      radiotherapy in ovarian cancer cell lines and in the progression of ovarian
      tumors. Survivin may also provide a pivotal prognostic implication for epithelial
      ovarian carcinomas.

PMID- 17200729
TI  - Pleiotropic effects of statins and related pharmacological experimental
      approaches.
AB  - Statins, the most widely prescribed cholesterol-lowering drugs, are considered to
      be first-line therapeutics for the prevention of coronary heart disease and
      atherosclerosis. Statins act by inhibiting the enzyme 3-hydroxy-3-methylglutaryl
      CoA (HMG-CoA) reductase, the rate-limiting enzyme in endogenous cholesterol
      biosynthesis, which catalyzes the reduction of HMG-CoA to mevalonic acid.
      Inhibition of this enzyme has proven to be effective for lowering plasma total
      cholesterol, low-density lipoprotein-cholesterol, and triglyceride levels in
      humans and can therefore be useful to treat atherosclerotic and dyslipidemic
      disorders. However, the clinical benefits of statins appear to extend beyond
      their lipid-lowering effects. Besides reducing cholesterol biosynthesis,
      inhibition of mevalonate by statins also leads to a reduction in the synthesis of
      important intermediates, such as the isoprenoids farnesyl pyrophosphate and
      geranylgeranyl pyrophosphate. These intermediates are involved in the
      posttranslational prenylation of several proteins (e.g., Ras, Rho, Rac) that
      modulate a variety of cellular processes including cellular signaling,
      differentiation, and proliferation. Given the central role of these isoprenylated
      proteins in endothelial function, atherosclerotic plaque stability, platelet
      activity, coagulation, oxidation, and inflammatory and immunologic responses, it
      could be anticipated that these compounds may exert multiple beneficial effects
      in a broad spectrum of disorders including cardiovascular disease, osteoporosis,
      Alzheimer's disease and related vascular dementia, viral and bacterial infection,
      etc. This article summarizes these cholesterol-lowering-independent effects of
      statins, termed "pleiotropic effects", and the underlying mechanisms, as well as
      the preclinical experimental approaches that would be useful to evaluate the
      effects of statins.

PMID- 17200730
TI  - Gateways to clinical trials.
AB  - 5-Methyltetrahydrofolate, (R)-flurbiprofen; Ad5CMV-p53, adalimumab, alefacept,
      alemtuzumab, Alequel, alicaforsen sodium, almotriptan, anakinra, aprepitant,
      aripiprazole, armodafinil; Bevacizumab, bortezomib, bosentan; Canfosfamide
      hydrochloride, ciclesonide, clofarabine, Cypher; Darbepoetin alfa, diclofenac
      potassium, drotrecogin alfa (activated), duloxetine hydrochloride; Eel
      calcitonin, eletriptan, eplerenone, everolimus, ezetimibe; Frovatriptan;
      Gefitinib, gamma-hydroxybutyrate sodium; HKI-272, HYB-165; Ibutamoren mesylate,
      imatinib mesylate, interleukin-21, ixabepilone; KRN-951; L-Arginine
      hydrochloride, levodopa/carbidopa/entacapone; Micafungin sodium, motexafin
      gadolinium, mycophenolic acid sodium salt; Nesiritide; Peginterferon alfa-2a,
      pitavastatin calcium, pralatrexate, pregabalin, pVAX/L523S-Ad.L523S; Rasagiline
      mesylate, recombinant human nerve growth factor, regadenoson, rF-PSA, rimonabant,
      rizatriptan, rofecoxib, rosuvastatin calcium, rV-B7.1, rV-PSA; Sipuleucel-T,
      sirolimus-eluting stent, solifenacin succinate, sorafenib, sunitinib malate;
      Talactoferrin alfa, Taxus, tegaserod maleate, teriparatide, tipifarnib;
      Valdecoxib, vandetanib, vatalanib succinate; WT1-peptide vaccine; Xaliproden
      hydrochloride. (c) 2006 Prous Science. All rights reserved.

PMID- 17200732
TI  - Time-resolved methods in biophysics. 3. Fluorescence lifetime correlation
      spectroscopy.
AB  - We present a thorough introduction into the recently developed fluorescence
      lifetime correlation spectroscopy (FLCS). The theoretical basis of FLCS is
      explained, and the method is applied to the study of a dynamic transition between
      two fluorescence lifetime states in a dye-protein complex.

PMID- 17200733
TI  - Proton translocation by the cytochrome bc1 complexes of phototrophic bacteria:
      introducing the activated Q-cycle.
AB  - The cytochrome bc1 complexes are proton-translocating, dimeric membrane
      ubiquinol:cytochrome c oxidoreductases that serve as "hubs" in the vast majority
      of electron transfer chains. After each ubiquinol molecule is oxidized in the
      catalytic center P at the positively charged membrane side, the two liberated
      electrons head out, according to the Mitchell's Q-cycle mechanism, to different
      acceptors. One is taken by the [2Fe-2S] iron-sulfur Rieske protein to be passed
      further to cytochrome c1. The other electron goes across the membrane, via the
      low- and high-potential hemes of cytochrome b, to another ubiquinone-binding site
      N at the opposite membrane side. It has been assumed that two ubiquinol molecules
      have to be oxidized by center P to yield first a semiquinone in center N and then
      to reduce this semiquinone to ubiquinol. This review is focused on the operation
      of cytochrome bc1 complexes in phototrophic purple bacteria. Their membranes
      provide a unique system where the generation of membrane voltage by light-driven,
      energy-converting enzymes can be traced via spectral shifts of native carotenoids
      and correlated with the electron and proton transfer reactions. An "activated Q
      cycle" is proposed as a novel mechanism that is consistent with the available
      experimental data on the electron/proton coupling. Under physiological
      conditions, the dimeric cytochrome bc1 complex is suggested to be continually
      primed by prompt oxidation of membrane ubiquinol via center N yielding a bound
      semiquinone in this center and a reduced, high-potential heme b in the other
      monomer of the enzyme. Then the oxidation of each ubiquinol molecule in center P
      is followed by ubiquinol formation in center N, proton translocation and
      generation of membrane voltage.

PMID- 17200734
TI  - Redox compounds influence on the NAD(P)H:FMN-oxidoreductase-luciferase
      bioluminescent system.
AB  - A review of the mechanisms of the exogenous redox compounds influence on the
      bacterial coupled enzyme system: NAD(P)H:FMN-oxidoreductase-luciferase has been
      done. A series of quinones has been used as model organic oxidants. The three
      mechanisms of the quinones' effects on bioluminescence were suggested: (1)
      inhibition of the NADH-dependent redox reactions; (2) interactions between the
      compounds and the enzymes of the coupled enzyme system; and (3) intermolecular
      energy migration. The correlation between the kinetic parameters of
      bioluminescence and the standard redox potential of the quinones proved that the
      inhibition of redox reactions was the key mechanism by which the quinones
      decrease the light emission intensity. The changes in the fluorescence anisotropy
      decay of the endogenous flavin of the enzyme preparations showed the direct
      interaction between quinones and enzymes. It has been demonstrated that the
      intermolecular energy migration mechanism played a minor role in the effect of
      quinones on the bioluminescence. A comparative analysis of the effect of
      quinones, phenols and inorganic redox compounds on bioluminescent coupled enzyme
      systems has been carried out.

PMID- 17200735
TI  - Conformational analysis of the blue-light sensing protein YtvA reveals a
      competitive interface for LOV-LOV dimerization and interdomain interactions.
AB  - The Bacillus subtilis protein YtvA is related to plant phototropins in that it
      senses UVA-blue-light by means of the flavin binding LOV domain, linked to a
      nucleotide-binding STAS domain. The structural basis for interdomain interactions
      and functional regulation are not known. Here we report the conformational
      analysis of three YtvA constructs, by means of size exclusion chromatography,
      circular dichroism (CD) and molecular docking simulations. The isolated YtvA-LOV
      domain (YLOV, aa 25-126) has a strong tendency to dimerize, prevented in full
      length YtvA, but still observed in YLOV carrying the N-terminal extension (N
      YLOV, aa 1-126). The analysis of CD data shows that both the N-terminal cap and
      the linker region (aa 127-147) between the LOV and the STAS domain are helical
      and that the central beta-scaffold is distorted in the LOV domains dimers. The
      involvement of the central beta-scaffold in dimerization is supported by docking
      simulation of the YLOV dimer and the importance of this region is highlighted by
      light-induced conformational changes, emerging from the CD data analysis. In
      YtvA, the beta-strand fraction is notably less distorted and distinct light
      driven changes in the loops/turn fraction are detected. The data uncover a common
      surface for LOV-LOV and intraprotein interaction, involving the central beta
      scaffold, and offer hints to investigate the molecular basis of light-activation
      and regulation in LOV proteins.

PMID- 17200736
TI  - 2,5-Dimethylphenacyl carbamate: a photoremovable protecting group for amines and
      amino acids.
AB  - 2,5-Dimethylphenacyl (DMP) carbamates (1a-c) released the corresponding free
      amines or amino acids in high chemical yields, albeit with quantum yields Phi of
      only 0.04-0.09, upon irradiation in either aprotic or protic solvents. The
      photoreaction proceeded principally from the triplet excited state via the E
      photoenol. The lifetimes of the triplet enol and the E- and Z-enols in the ground
      state were determined by laser flash photolysis. The primary photoinitiated
      transformation liberated a carbamic acid derivative, which subsequently
      decarboxylated to the amino group-containing compound. Exhaustive irradiation of
      a DMP-protected aniline (1a) in acetonitrile did not provide aniline in
      quantitative chemical yields, because it was involved in reductive cleavage of
      the starting material as an electron donor, thereby decreasing the overall
      deprotection yield (86%). Phenylalanine methyl ester, liberated from 1c, was,
      however, obtained in excellent chemical yield (97%). It was also found that the
      carbamates, while thermally stable, released amines with higher quantum yields in
      acidic methanol solutions. The DMP chromophore is proposed as an excellent
      photoremovable protecting group for amino acids and, under specific conditions,
      for amines in organic synthesis and biochemistry.

PMID- 17200737
TI  - The solar UV radiation level needed for cutaneous production of vitamin D3 in the
      face. A study conducted among subjects living at a high latitude (68 degrees N).
AB  - Populations at high latitudes experience several winter months with insufficient
      UV solar radiation to induce a significant cutaneous production of vitamin D.
      This unique study was designed to pursue an in vivo threshold of UV radiation
      needed for cutaneous production of vitamin D to take place if only the face was
      exposed to UV radiation. The vitamin D status were measured by analyzing blood
      samples weekly from a study group of 15 subjects over a period of 2 months during
      late winter, when UV radiation can be expected to increase substantially from
      rising solar elevations. Statistical analysis showed no significant positive
      association between the mean UV radiation dose and the mean 25(OH)D (25-hydroxy
      vitamin D) for the group. On an individual basis, however, we found indications
      that subjects with very low initial concentration of 25(OH)D (<30 nmol l(-1))
      seemed to respond to UV radiation as early as in the beginning of March. For
      other individuals diet seemed to be the dominant controlling factor for 25(OH)D
      levels.

PMID- 17200738
TI  - A dye-sensitized solar cell driven electrochromic device.
AB  - A new dye-sensitized solar cell driven electrochromic device has been fabricated.
      The device consists of an electrochromic display and a solar cell in a single
      nanocrystalline film. The optimization of the electrochromic and the solar cell
      functions was carried out. An applied potential of 1.0 V was required for
      coloring and the best solar energy conversion efficiency 1.1% was achieved. The
      efficiency may be compared to an efficiency of 4.6% obtained in a similar dye
      sensitized solar cell without the display property. Coloring and bleaching times
      of the device were less than one second and a transmittance change from 38.7%
      (bleached) to 15.9% (colored) at best was achieved. The optimization of the
      electrochromic property of the device lead to decreasing efficiency of the solar
      cell and vice versa.

PMID- 17200739
TI  - Effect of low-level alpha-radiation on bioluminescent assay systems of various
      complexity.
AB  - This study addresses the effects of low-level alpha-radiation on bioluminescent
      assay systems of different levels of organization: in vivo and in vitro. Three
      bioluminescent assay systems are used: intact bacteria, lyophilized bacteria, and
      bioluminescent system of coupled enzyme reactions. Solutions of 241Am(NO3)3 are
      used as a source of alpha-radiation. It has been shown that activation processes
      predominate in all the three bioluminescent assay systems subjected to short-term
      exposure (20-55 h) and inhibition processes in the systems subjected to longer
      term exposure to radiation. It has been found that these effects are caused by
      the radiation component of 241Am3+ impact. The intensity of the 241Am3+ effect on
      the bioluminescent assay systems has been shown to depend on the 241Am3+
      concentration, level of organization and integrity of the bioluminescent assay
      system. The bioluminescent assay systems in vivo have been found to be highly
      sensitive to 241Am3+ (up to 10(-17) M).

PMID- 17200740
TI  - Fluorescent dyes undergoing intramolecular proton transfer with improved
      sensitivity to surface charge in lipid bilayers.
AB  - 4'-(Dialkylamino)-3-hydroxyflavones are characterized by an excited-state proton
      transfer reaction between two tautomeric excited states, which results in two
      emission bands well separated on the wavelength scale. Due to the high
      sensitivity of the relative intensities of the two emission bands to solvent
      polarity, hydrogen bonding and local electric fields, these dyes found numerous
      applications in biomembrane studies. In order to further improve their
      fluorescence characteristics, we have synthesized new dyes where the 2-phenyl
      group is substituted with a 2-thienyl group. In organic solvents, the new dyes
      exhibit red shifted absorption and dual fluorescence. Although they show lower
      sensitivity to solvent polarity and H-bond donor ability (acidicity) than their
      parent 3-hydroxyflavone dyes, they exhibit a much higher sensitivity to solvent H
      bond acceptor ability (basicity). Moreover, when tested in lipid vesicles of
      different surface charge, the new dyes show much better resolved dual emission
      and higher sensitivity to the surface charge of lipid bilayers than the parent
      dyes. The response of the new dyes to surface charge is probably connected with
      the H-bond basicity of the membrane surface, which is the highest for negatively
      charged surfaces. As a consequence, the new dyes appear as prospective
      fluorophores for the development of new fluorescent probes for biomembranes.

PMID- 17200741
TI  - Visible light decomposition of ammonia to N2 with Ru(bpy)3(2+) sensitizer.
AB  - Visible light decomposition of aqueous NH3 to N2 was investigated using a
      photocatalyst aqueous solution based on molecular photoelectron relay systems of
      either sensitizer (tris(2,2'-bipyridine)ruthenium(II), (Ru(bpy)3(2+))/potassium
      peroxodisulfate(K(2)S(2)O(8)) or Ru(bpy)3(2+)/methylviologen dichloride(MV2+)/O2,
      capable of using visible light instead of UV-driven semiconductors such as TiO2.
      It was confirmed by using an in situ visible absorption spectral change under
      irradiation that the Ru(II) complex is oxidized to the Ru(III) complex by
      K(2)S(2)O(8), and that the Ru(III) complex formed is stable without NH3, while
      the added NH3 was oxidized by the Ru(III) complex to produce the Ru(II) complex.
      In the presence of 1 mM NH3 aqueous solution, the Ru(III) complex was the
      predominant species under the photostationary state, but in the presence of 100
      mM NH3, Ru(II) predominated. Gas-chromatographic analysis of the gaseous phase in
      the presence of 8.1 M NH3 showed that the photochemical oxidation of ammonia
      yielded N2. It was also demonstrated by using the in situ visible absorption
      spectrum under irradiation of the NH3 (1 M)/Ru(bpy)3(2+) (0.1 mM)/MV2+ (10 mM)
      system under Ar that MV+* is accumulated, showing that NH3 works as an electron
      donor for MV+* accumulation with simultaneous formation of the oxidized product
      of ammonia ((NH3)ox) without producing N2. It was suggested that the reduced
      product (MV+*) and the oxidized product ((NH3)ox) are in a kind of dynamic
      equilibrium prohibiting further oxidation of (NH3)ox by Ru(bpy)3(3+) to N2. In
      the O2 atmosphere, the oxidation of MV+* to MV2+ takes place to accumulate
      Ru(III) complex, so that (NH3)ox was further oxidized to N2. The high activity of
      IrO2 as a cocatalyst in this system was demonstrated.

PMID- 17200742
TI  - Differential interactions of phytochrome A (Pr vs. Pfr) with monoclonal
      antibodies probed by a surface plasmon resonance technique.
AB  - Phytochromes are red- and far-red light-reversible photoreceptors for
      photomorphogenesis in plants. Phytochrome A is a dimeric chromopeptide that
      mediates very low fluence and high irradiance responses. To analyze the surface
      properties of phytochrome A (phyA), the epitopes of 21 anti-phyA monoclonal
      antibodies were determined by variously engineered recombinant phyA proteins and
      the dissociation constants of seven anti-phyA monoclonal antibodies with phyA
      were measured using a surface plasmon resonance (SPR)-based resonant mirror
      biosensor (IAsys). Purified oat phyA was immobilized on the sensor surface using
      a carboxymethyl dextran cuvette in advance, and the interactions of each chosen
      monoclonal antibody against phyA in either red light absorbing form (Pr) or far
      red light absorbing form (Pfr) at different concentrations were monitored. The
      binding profiles were analyzed using the FAST Fit program of IAsys. The resultant
      values of dissociation constants clearly demonstrated the differential affinities
      between the phyA epitopes and the monoclonal antibodies dependent upon Pr vs. Pfr
      conformations. Monoclonal antibody mAP20 preferentially recognized the epitope at
      amino acids 653-731 in the Pr form, whereas mAA02, mAP21 and mAR07/mAR08
      displayed preferential affinities for the Pfr's surfaces at epitopes 494-601 (the
      hinge region between the N- and C-terminal domains), 601-653 (hinge in PASI
      domain), and 772-1128 (C-terminal domain), respectively. The N-terminal extension
      (1-74) was not recognized by mAP09 and mAP15, suggesting that the N-terminal
      extreme is not exposed in the native conformation of phyA. On the other hand, the
      C-terminal domain becomes apparently exposed on Pr-to-Pfr phototransformation,
      suggesting an inter-domain cross-talk. The use of surface plasmon resonance
      spectroscopy offers a new approach to study the surface properties of
      phytochromes associated with the photoreversible structural changes, as well as
      for the study of protein-protein interactions of phytochromes with their
      interacting proteins involved in light signaling events in plants.

PMID- 17200743
TI  - Three dimensional visualisation of human facial exposure to solar ultraviolet.
AB  - A three dimensional computer model of the human face has been developed to
      represent solar ultraviolet exposures recorded by dosimeter measurements on a
      manikin headform under low cloud conditions and various solar zenith angles.
      Additionally, polysulfone dosimeters have been successfully miniaturised to
      provide the detailed measurements required across the face. The headform used in
      this research was scanned at 709 individual locations to make a wireframe mesh
      consisting of 18 vertical contours and 49 horizontal contours covering half the
      manikin's frontal facial topography. Additionally, the back of the headform and
      neck have also been scanned at 576 locations. Each scanned location has been used
      as a viable dosimeter position on the headform and represents a grid intersection
      point on the developed computer wireframe. A series of exposures recorded by
      dosimeters have been translated into three dimensional exposure ratio maps,
      representing ambient solar ultraviolet exposure. High dosimeter density has
      allowed for the development of individual topographic contour models which take
      into account complex variation in the face and improve upon previously employed
      techniques which utilise fewer dosimeters to interpolate exposure across facial
      contours. Exposure ratios for solar zenith angle ranges of 0 degrees -30 degrees,
      30 degrees -50 degrees, and 50 degrees -80 degrees have been developed.

PMID- 17200744
TI  - ESIPT-exhibiting protein probes: a sensitive method for rice proteins detection
      during starch extraction.
AB  - The 2-(4'-isothiocyanate-2'-hydroxyphenyl)benzoxazole dye was successfully
      applied as label of rice proteins during the alkaline extraction of starch.
      Direct fluorescence measurements were used to observe the presence of proteins
      labelled in different steps of rice starch extraction. The results were compared
      to those obtained with the well-known biuret colorimetric test. Whereas the
      colorimetric test indicates the absence of protein after the third extraction
      step, the fluorescence emission of the conjugate could be observed in all
      extraction steps. The separation of different rice proteins could also be
      observed.

PMID- 17200745
TI  - Excitation-induced dynamics of external pH pattern in Chara corallina cells and
      its dependence on external calcium concentration.
AB  - The influence of cell excitation and external calcium level on the dynamics of
      light-induced pH bands along the length of Chara corallina cells is studied in
      the present paper. Generation of an action potential (AP) transiently quenched
      these pH patterns, which was more pronounced at 0.05-0.1 mM Ca2+ than at higher
      concentrations of Ca2+ (0.6-2 mM) in the medium. After transient smoothing of the
      pH bands, some alkaline peaks reemerged at slightly shifted positions in media
      with low Ca2+ concentrations, while at high Ca2+ concentrations, the alkaline
      spots reappeared exactly at their initial positions. This Ca2+ dependency has
      been revealed by both digital imaging and pH microelectrodes. The stabilizing
      effect of external Ca2+ on the locations of recovering alkaline peaks is
      supposedly due to formation of a physically heterogeneous environment around the
      cell owing to precipitation of CaCO3 in the alkaline zones at high Ca2+ during
      illumination. The elevation of local pH by dissolving CaCO3 facilitates the
      reappearance of alkaline spots at their initial locations after temporal
      suppression caused by cell excitation. At low Ca2+ concentrations, when the
      solubility product of CaCO3 is not attained, the alkaline peaks are not
      stabilized by CaCO3 dissolution and may appear at random locations.

PMID- 17200747
TI  - Engineering of mesostructured silicas by pseudomorphism.
AB  - Pseudomorphic transformation is introduced as an effective and versatile method
      to independently optimize the morphology of the grains and the structural
      properties of mesostructured silicas. In this account a short overview is given
      of the preparation of MCM-41 and MCM-48 mesophases as non-aggregated and
      homogeneously distributed particles with sizes ranging from 5 to 800 microm.

PMID- 17200748
TI  - Synthesis and characterization of a spin crossover iron(II)-iron(III) mixed
      valence supramolecular pseudo-dimer exhibiting chiral recognition, hydrogen
      bonding, and pi-pi interactions.
AB  - Reaction of iron(II) and the 3 : 1 Schiff base condensate of 5-methylpyrazole-3
      carboxaldehyde and tris(2-aminoethyl)amine in air gives a pseudo-dimer complex
      with a triple helix structure made of Delta-Delta and Lambda-Lambda pairings of
      spin crossover iron(II) and low spin iron(III) cations that are held together by
      three pi-pi and hydrogen bonding interactions.

PMID- 17200746
TI  - Effect of water molecules on the fluorescence enhancement of Aflatoxin B1
      mediated by Aflatoxin B1:beta-cyclodextrin complexes. A theoretical study.
AB  - In order to explain the observed fluorescence enhancement of Aflatoxin B1 (AFB1)
      when forming AFB1:beta-cyclodextrin (AFB1:beta-CD) inclusion complexes, we have
      performed a theoretical (quantum chemistry calculations) study of AFB1 and
      AFB1:beta-CD in vacuum and in the presence of aqueous solvent. The AM1 method was
      used to calculate the absorption and emission wavelengths of these molecules.
      With the help of density functional theory (DFT) and time-dependent DFT (TDDFT)
      vibrational frequencies and related excitation energies of AFB1 and AFB1.(H2O)m =
      4,5,6,11 were calculated. On the basis of these calculations we propose a
      plausible mechanism for the fluorescence enhancement of AFB1 in the presence of
      beta-CD: (1) before photoexcitation of AFB1 to its S1 excited state, there is a
      vibrational coupling between the vibrational modes involving the AFB1 carbonyl
      groups and the bending modes of the nearby water molecules (CG + WM); (2) these
      interactions allow a thermal relaxation of the excited AFB1 molecules that
      results in fluorescence quenching; (3) when the AFB1 molecules form inclusion
      complexes with beta-CD the CG + WM interaction decreases; and (4) this gives rise
      to a fluorescence enhancement.

PMID- 17200749
TI  - Pi-pi stacking assisted binding of aromatic amino acids by copper(II)-aromatic
      diimine complexes. Effects of ring substituents on ternary complex stability.
AB  - Ternary Cu(ii) complexes containing an aromatic diimine (DA = di(2
      pyridylmethyl)amine (dpa), 4,4'-disubstituted 2,2'-bipyridine (Y(2)bpy; Y = H
      (bpy), Me, Cl, N(Et)(2), CONH(2) or COOEt) or 2,2'-bipyrimidine) and an aromatic
      amino acid (AA = l-phenylalanine (Phe), p-substituted phenylalanine (XPhe; X =
      NH(2), NO(2), F, Cl or Br), l-tyrosine (Tyr), l-tryptophan (Trp) or l-alanine
      (Ala)) were characterized by X-ray diffraction, spectroscopic and potentiometric
      measurements. The structures of [Cu(dpa)(Trp)]ClO(4).2H(2)O and
      [Cu((CONH(2))(2)bpy)(Phe)]ClO(4).H(2)O in the solid state were revealed to have
      intramolecular pi-pi interactions between the Cu(ii)-coordinated aromatic ring
      moiety, Cu(DA) (Mpi), and the side chain aromatic ring of the AA (Lpi). The
      intensities of Mpi-Lpi interactions were evaluated by the stability constants of
      the ternary Cu(ii) complexes determined at 25 degrees C and I = 0.1 M (KNO(3)),
      which revealed that the stability enhancement of the Cu(DA)(AA) systems due to
      the interactions is in the order (CONH(2))(2)bpy < bpy < Me(2)bpy <
      (Et(2)N)(2)bpy with respect to DA. The results indicate that the electron density
      of coordinated aromatic diimines influences the intensities of the stacking
      interactions in the Cu(DA)(AA) systems. The Mpi-Lpi interactions are also
      influenced by the substituents, X, of Lpi and are in linear relationship with
      their Hammett sigma(p) values with the exception of X = Cl and Br.

PMID- 17200750
TI  - Preparation and characterization of mixed-ligand cobalt(III) complexes containing
      (3-aminopropyl)dimethylphosphine (pdmp). Conformation of the six-membered pdmp
      chelate ring.
AB  - Several new cobalt(III) complexes containing (3-aminopropyl)dimethylphosphine
      (pdmp) have been prepared, and their molecular structures have been determined. A
      dichloro complex of trans(Cl,Cl)-cis(P,P)-[CoCl(2)(pdmp)(2)]PF(6) (1) was
      prepared from trans-[CoCl(2)(py)(4)]Cl.6H(2)O and pdmp. X-Ray crystallography
      confirmed the (C(2))-chair(2) conformation of two six-membered pdmp chelate rings
      in 1, while the analogous 1,3-bis(dimethylphosphino)propane (dmpp) complex trans
      [CoCl(2)(dmpp)(2)]ClO(4) (3) exhibited the (D(2d))-twist(2) conformation.
      Substitution reactions of 1 for ethane-1,2-diamine (en), pentane-2,4-dionate
      (acac), and N,N-dimethyldithiocarbamate (dtc) gave the mixed-ligand tris(chelate)
      type complexes of [Co(en)(2)(pdmp)]Cl(2)(PF(6)) (5),
      [Co(acac)(pdmp)(2)](PF(6))(2) (7), and [Co(dtc)(3-n)(pdmp)(n)](PF(6))(n) [n = 1
      (9) or 2 (10)], respectively. The conformer of the complex cation in 5 was
      assigned as lel.ob.chair by X-ray analysis. In the case of the acac complex 7,
      both trans(P,N) (7a) and trans(N,N) (7b) isomers were isolated, and the complex
      cations were characterized as syn-chair(2) and anti-chair(2) conformers,
      respectively, with respect to the six-membered pdmp chelate rings. These
      conformers coincide with the most stable ones anticipated by the DFT optimum
      geometry calculations. In the crystal structure of trans(P,N)
      [Co(dtc)(pdmp)(2)](BPh(4))(2) (10') one of the pdmp chelate rings adopted a skew
      boat (twist) conformation, which reduced the intramolecular steric ring-ring
      interaction effectively. The DFT optimized geometries for several isomers and/or
      conformers of [CoCl(2)(pdmp)(2)](+) were compared.

PMID- 17200751
TI  - Grafting of cyclopentadienyl ruthenium complexes on aminosilane linker modified
      mesoporous SBA-15 silicates.
AB  - Cyclopentadienyl ruthenium phosphane and carbene complexes are grafted on the
      surface of mesoporous SBA-15 molecular sieves through an aminosilane linker. The
      nature of the support after the grafting is examined by powder XRD, TEM and N(2)
      adsorption/desorption analysis. Elemental analysis, FT-IR, DRIFTS, TG-MS and MAS
      NMR studies confirm the successful grafting of the complexes on the surface. The
      grafted materials are applied for catalytic aldehyde olefination and
      cyclopropanation.

PMID- 17200752
TI  - New bimetallic compounds based on the bis(thiosemicarbazonato) motif.
AB  - Zinc and copper bis(thiosemicarbazonato) complexes containing more than one metal
      centre have been prepared with a view to examining their application for
      molecular imaging. The zinc complexes are fluorescent with excitation and
      emission at relatively long wavelengths. The dinuclear copper complex undergoes
      two sequential, quasi-reversible reductions.

PMID- 17200753
TI  - Synthesis, structure and properties of {M4O4} cubanes containing nickel(II) and
      cobalt(II).
AB  - A survey of the crystal structures containing simple {M4O4} cubane units is
      reported. It shows that the average M-M distance in these complexes is relatively
      constant for a given metal ion M. The structures are all distorted from the
      idealised cube to a T(d) structure, and most show a further distortion which,
      however, usually maintains some elements of symmetry. A system for classifying
      the different types of ligand in these complexes is proposed. Two new cubanes of
      cobalt(II) and nickel(II) with the ligand (R,R)-bis-1,2-(1-methylbenzimidazol-2
      yl)ethane-1,2-diol, (R,R)- or its enantiomer have been isolated and the crystal
      structure of the cobalt(II) complex confirms the cubane structure. Electronic, CD
      and (1)H NMR spectra and magnetic susceptibility data are reported. The magnetic
      data for these and other compounds in the literature are discussed in terms of
      the structural parameters.

PMID- 17200754
TI  - Magnetic properties and molecular structures of binuclear (2-pyrazinecarboxylate)
      bridged complexes containing Re(IV) and M(II) (M = Co, Ni).
AB  - Three novel Re(iv) compounds, the mononuclear complex Bu(4)N[ReBr(5)(Hpyzc)] (1)
      and the heterobimetallic complexes [ReBr(5)(mu-pyzc)M(dmphen)(2)].2CH(3)CN [M =
      Co (2), Ni (3)] (Hpyzc = 2-pyrazinecarboxylic acid, dmphen = 2,9-dimethyl-1,10
      phenanthroline), have been synthesized and their crystal structures determined by
      single-crystal X-ray diffraction. The structure of 1 consists of
      [ReBr(5)(Hpyzc)](-) complex anions and tetrabutylammonium cations, Bu(4)N(+). The
      Re(iv) is surrounded by five bromide anions and a N-donor Hpyzc monodentate
      ligand, in a distorted octahedral environment. The structures of 2 and 3 consist
      of dinuclear units [ReBr(5)(mu-pyzc)M(dmphen)(2)], with the metal ions linked by
      a pyzc bridge ligand, being bidentate toward M(II) and monodentate toward Re(IV).
      The environment of Re(IV) is the same as in 1, whereas M(II) is six-coordinate,
      being surrounded by four nitrogen atoms of two bidentate dmphen ligands and one
      oxygen atom and one nitrogen atom of the pyzc anion. The magnetic properties of 1
      3 were investigated in the temperature range 2.0-300 K. 1 shows the expected
      magnetic behavior for a mononuclear Re(IV) complex with a weak intermolecular
      antiferromagnetic coupling at low temperatures. The bimetallic complexes exhibit
      an intramolecular ferromagnetic coupling between Re(IV) and the M(II) ion (Co,
      Ni).

PMID- 17200755
TI  - A cadmium hydroxide complex of a N3S-donor ligand containing two hydrogen bond
      donors: synthesis, characterization, and CO2 reactivity.
AB  - Treatment of the ebnpa (N-2-(ethylthio)ethyl-N,N-bis((6-neopentylamino-2
      pyridyl)methyl)amine) ligand with a molar equivalent amount of
      Cd(ClO(4))(2).5H(2)O in CH(3)CN followed by the addition of [Me(4)N]OH.5H(2)O
      yielded the cadmium hydroxide complex [(ebnpaCd)(2)(mu-OH)(2)](ClO(4))(2) (1).
      Complex 1 has a binuclear cation in the solid-state with secondary hydrogen
      bonding and CH/pi interactions involving the ebnpa ligand. In acetonitrile, 1
      forms a binuclear/mononuclear equilibrium mixture. The formation of a mononuclear
      species has been confirmed by conductance measurements of 1 at low
      concentrations. Variable temperature studies of the binuclear/mononuclear
      equilibrium provided the standard enthalpy and entropy associated with the
      formation of the monomer as DeltaH degrees = +31(2) kJ mol(-1) and DeltaS degrees
      = +108(8) J mol(-1) K(-1), respectively. Enhanced secondary hydrogen-bonding
      interactions involving the terminal Cd-OH moiety may help to stabilize the
      mononuclear complex. Treatment of 1 with CO(2) in acetonitrile results in the
      formation of a binuclear cadmium carbonate complex, [(ebnpaCd)(2)(mu
      CO(3))](ClO(4))(2) (2).

PMID- 17200756
TI  - Synthesis and structures of bimetallic and polymeric zinc coordination compounds
      supported by salicylaldiminato and anilido-aldimine ligands.
AB  - A series of bimetallic zinc complexes bearing salicylaldiminato (1b-3b) or
      anilido-aldimine (4c-5c) ligand frameworks, in which the metal centres are
      separated by aliphatic spacer groups containing 3-6 methylene units, were
      targeted. X-Ray analysis of salicylaldiminato derivative 2b, with a 4 carbon
      spacer group, revealed a coordination polymer in the solid state where each zinc
      centre is ligated by two salicylaldiminato ligands. Contrastingly, the structure
      of the anilido-aldimine complex 4c, with a 3 carbon methylene spacer group, was
      found to be a discrete bimetallic complex. These differences are attributed to
      the differing steric protection at the anilido vs phenoxy donors, the latter more
      readily facilitating bridges between metal centres.

PMID- 17200757
TI  - Density functional theory study of twelve-atom germanium clusters: conflict
      between the Wade-Mingos rules and optimum vertex degrees.
AB  - Density functional theory (DFT) at the hybrid B3LYP level has been applied to
      Ge(12)(z) bare germanium clusters (z = -6, -4, -2, 0, +2, +4, +6) starting from
      11 initial configurations. The Wade-Mingos rules are seen to have limited value
      in rationalizing the results since they frequently require vertex degrees higher
      than the optimum vertex degree of 4 for germanium. Thus the expected I(h) regular
      icosahedron is no longer the global minimum for Ge(12)(2-) although it remains a
      low energy structure for Ge(12)(2-) lying only 5.6 kcal mol(-1) above a bicapped
      arachno structure conforming to the Wade-Mingos rules. The three lowest energy
      structures for Ge(12)(4-) within 11 kcal mol(-1) are a prolate (elongated)
      polyhedron with six quadrilateral faces and eight triangular faces, the dual of
      the bisdisphenoid with four trapezoidal and four pentagonal faces, and a
      polyhedron with two quadrilateral and 16 triangular faces related but not
      identical to the polyhedron found in the known tetracarbon carboranes
      R(4)C(4)B(8)H(8). The lowest energy structures for the neutral Ge(12) are seen to
      be distorted versions of the icosahedron and the bicapped 10-vertex arachno
      lowest energy structures for Ge(12)(2-). The low energy structures for the even
      more hypoelectronic Ge(12)(2+) and Ge(12)(4+) are even more unusual including a
      hexacapped octahedron, a tetracapped square antiprism, and a double cube for
      Ge(12)(2+) and a C(2v) structure with a central unique degree 6 vertex for
      Ge(12)(4+).

PMID- 17200759
TI  - Multidimensional NMR spectroscopy for the study of histone H4-Ni(II) interaction.
AB  - The N-terminal 30-amino acid tail of histone H4, a nuclear protein, was studied
      as a model for the interaction of this protein with Ni(ii) ions. The behaviour of
      the ends-blocked Ac-SGRGKGGKGLGKGGA(15)K(16)R(17)H(18)R(19)KVLRDNIQGIT-Am
      fragment towards Ni(ii) was analyzed with multidimensional NMR (1D, 2D TOCSY,
      NOESY) and UV-Vis spectroscopy. As expected, the coordination involved the
      imidazolic nitrogen of the His(18) residue and the three deprotonated amidic
      nitrogens of the His(18), Arg(17) and Lys(16) residues, respectively. A model for
      the structure of the complex was calculated from the inter-residual NOEs recorded
      in 2D NOESY spectra. The structure obtained shows that the interaction with the
      metal is responsible for deep changes in the conformation of the peptide,
      blocking the side chain of Arg(17) and Lys(16) residues above the coordination
      plane. These structural modifications may be physiologically relevant to the
      mechanism of nickel carcinogenesis.

PMID- 17200758
TI  - Molecular and electronic structure of square planar complexes [PdII(tbpy)(L N,O
      IP)]0, [PdII(tbpy)(LN,O ISQ)](PF6), and [PdII(tbpy)(L N,O
      IBQ)](PF6)(BF4).2CH2Cl2: an o-iminophenolato based ligand centered, three
      membered redox series.
AB  - Three Pd(II) complexes which are members of the same electron-transfer series
      have been synthesized. Refluxing of the reaction mixture containing equimolar
      amounts of PdCl(2), 2-(2-trifluoromethyl)anilino-4,6-di-tert-butylphenol
      (H(2)L(N,O)), 4,4'-di-tert-butyl-2,2'-dipyridyl ((t)bpy), and 3 equiv of
      triethylamine in MeOH under an argon atmosphere followed by exposure to air and
      addition of KPF(6) after cooling to room temperature yields reddish brown
      crystals of paramagnetic (S = 1/2) [Pd(L(N,O)(ISQ))((t)bpy)](PF6) (2). Reaction
      of 2 with one equiv of [CoCp2] in dry and degassed CH(2)Cl(2) using anaerobic
      conditions gives diamagnetic [Pd(L(N,O)(IP))((t)bpy)] (1), which is the one
      electron reduced form of 2. One-electron oxidation of 2 in CH(2)Cl(2) under argon
      with one equiv of NOBF4 affords diamagnetic
      [Pd(L(N,O)(IBQ))((t)bpy)](PF6)(BF4).2CH(2)Cl(2) (3). Complexes 1, 2, and 3
      constitute three members of the same electron-transfer series. They are ideally
      suited to distinctly distinguish the geometrical and spectroscopic features of
      the N,O-coordinated, closed-shell, diamagnetic o-iminophenolate (L(N,O)(IP))2-,
      the corresponding open-shell pi-radical o-iminobenzosemiquinonate (L(N,O)(ISQ))1
      .(S(rad) = 1/2), and the closed-shell o-iminobenzoquinone (L(N,O)(IBQ))0 forms.
      All complexes were characterized by X-ray crystallography (100 K), cyclic
      voltammetry, EPR, and UV-vis spectroscopy. Complex 2 exhibits three reversible
      electron transfer waves in the cyclic voltammogram. Structural characterization
      of complex 3 reveals an interesting strong ion pairing between the BF4 anion and
      the complex dication with a short C-F distance of 2.7 A.

PMID- 17200760
TI  - Thrombosis and Haemostasis: an interdisciplinary and translational endeavour.

PMID- 17200761
TI  - Antioxidative defense in endothelial cells: new kids on the block.

PMID- 17200762
TI  - Alternatively spliced tissue factor - one cut too many?

PMID- 17200763
TI  - Tissue factor-positive microparticles in blood associated with coagulopathy in
      cancer.

PMID- 17200764
TI  - Alternatively spliced human tissue factor (asHTF) is not pro-coagulant.
AB  - It has been proposed that alternatively-spliced human tissue factor (asHTF) is
      pro-coagulant. We have evaluated the function of asHTF in a mammalian expression
      system. Full-length human tissue factor (HTF) and asHTF were cloned from smooth
      muscle cells and over-expressed in HEK293 cells. As expected, a marked pro
      coagulant activity (FX activation, thrombin generation) was observed on the
      surface, in lysates, and on microparticles from HTF transfected cells. In
      contrast, no pro-coagulant activity of asHTF was observed.

PMID- 17200765
TI  - Rapid activation of haemostasis after hormonal emergency contraception.
AB  - Hormonal emergency contraception (EC) is a well established contraceptive method,
      recommended to all women, although the effects on haemostais are not fully
      evaluated. The aim of this study was to evaluate whether exposure to EC has
      effects on well established cardiovascular risk factors, and also to examine
      whether differences exist between two EC treatments. In a prospective randomized
      cross over design 11 women used two different EC methods, one with estrogen and
      levonorgestrel (EE-EC) and one with levonorgestrel only (LNG-EC). Plasma
      concentrations of haemostatic factors (APC resistance, antithrombin, fibrinogen,
      prothrombin fragment 1 + 2, free protein S, factorVII and PAI-1), sex-hormone
      binding globulin (SHBG), the apolipoprotein (apo)B/apoA1 ratio and C-reactive
      protein (CRP) were followed frequently during the following 48 hours. A rapid
      haemostatic activation was induced with both treatments, although more pronounced
      with EE-EC. Already two hours after EC, the plasma concentrations of haemostatic
      parameters and SHBG were significantly different from baseline concentrations. An
      ETP-based APC-resistance method showed increased APC resistance with EE-EC and
      decreased APC resistance with LNG-EC. The ApoB/ApoA1 ratio was affected in a
      favourable direction with EE-EC.CRP increased slightly regardless of treatment.
      Even a very short exposure to exogenous sex hormones causes prompt effects on
      hepatic protein synthesis and the coagulation system. This must be taken into
      consideration whenever exogenous steroid hormones are administered, especially to
      individuals with a genetic predisposition to thrombosis or transiently disturbed
      haemostasis.

PMID- 17200766
TI  - Relatively increased von Willebrand factor activity after off-pump coronary
      artery bypass graft surgery.
AB  - High shear forces can induce structural changes in the shape of the von
      Willebrand factor (VWF) molecule, making it more sensitive for ADAMTS-13, a
      specific VWF protease. This leads to proteolysis of the highest-molecular-weight
      multimers, which are the most effective in platelet-mediated hemostasis under
      conditions of high shear stress. The use of cardiopulmonary bypass (CPB) is
      accompanied with high shear forces and could therefore lead to diminished VWF
      activity. Therefore, we studied VWF activity in patients undergoing myocardial
      revascularization. We enrolled 60 patients undergoing coronary artery bypass
      graft (CABG) surgery with and without CPB (30 in each group). ADAMTS-13 activity,
      VWF antigen (VWF:Ag) and propeptide levels were measured directly before and
      after the procedure. VWF activity was determined using both the ristocetin
      cofactor activity (VWF:Rcof) and collagen binding (VWF:CB) assays. VWF:Rcof and
      VWF:CB, both corrected for VWF:Ag, were significantly increased after the
      procedure in the off-pump group (p < 0.001 and p = 0.05, respectively), but not
      in the CPB group. Postoperative VWF:Ag and VWF-propeptide levels significantly
      increased in both groups. ADAMTS-13 activity increased after both types of
      surgery after correction for hemodilution. Postoperative VWF:Rcof levels
      correlated with postoperative D-dimer levels (p = 0.025) and were associated with
      early cognitive decline in the off-pump group (p = 0.025). Our data indicate that
      VWF activity is increased after off-pump CABG, but not after CABG with CPB. Since
      release of VWF is comparable in both groups, shear stress-induced proteolysis due
      to the use of CPB may be responsible for the decreased VWF activity.

PMID- 17200767
TI  - Clot structure modification by fondaparinux and consequence on fibrinolysis: a
      new mechanism of antithrombotic activity.
AB  - Fondaparinux is a synthetic pentasaccharide consisting of the minimal sequence of
      heparin which interacts with antithrombin (AT). It represents a new class of
      selective factor Xa inhibitors without any antithrombin activity. It has been
      shown to exhibit potent antithrombotic properties in clinical studies. However,
      the mechanism of its antithrombotic action has not yet been fully established. In
      the present study it was shown that fondaparinux, used at pharmacological
      concentration (500 ng/ml), rendered the clot more susceptible to fibrinolysis
      induced by t-PA: plasma fibrin clots formed in the presence of fondaparinux and
      perfused with t-PA were degraded at a faster rate than those formed in the
      absence of fondaparinux. This fibrinolytic activity of fondaparinux is mainly due
      to a modification of clot structure characterized by a loose fibrin conformation
      with less branched fibers and the presence of large pores in comparison to
      control clots which present a tighter conformation. The difference in fibrin
      structure was responsible for an increase in clot porosity leading to a better
      availability of t-PA to the fibrin network. It is related to the decrease in
      thrombin generation, in an AT-dependent pathway. It was also demonstrated that in
      the presence of exogenous thrombomodulin, the inhibition of TAFI activation by
      fondaparinux could contribute, to a lesser extent, to the increased thrombus
      lysis. The increase in t-PA induced thrombus lysis could contribute to the
      antithrombotic activity of fondaparinux.

PMID- 17200768
TI  - No interaction between factor V Leiden and hyperhomocysteinemia or MTHFR 677TT
      genotype in venous thrombosis. Results of a meta-analysis of published studies
      and a large case-only study.
AB  - Homocysteine may have a thrombogenic effect through inhibition of inactivation of
      factor Va by activated protein C. Because factor V Leiden also leads to
      resistance of factor V to activated protein C, it would be possible that both
      factors show interaction for the risk of venous thrombosis. This has been
      reported in some studies, but not in others. We performed a metaanalysis to
      investigate a possible interaction between factor V Leiden and
      hyperhomocysteinemia, including 825 subjects with venous thrombosis and 2,109
      controls, for the risk of venous thrombosis. In addition, we assessed a possible
      interaction between factor V Leiden and MTHFR 677TT genotype (the most common
      genetic determinant of homocysteine levels), including 2,547 subjects with venous
      thrombosis and 4,327 controls. We also investigated the interaction effect of
      factor V Leiden and hyperhomocysteinemia in a large case-only study using data of
      the VITRO study, including 2,077 subjects with first-time venous thrombosis. The
      meta-analysis yielded no evidence for additive or multiplicative interaction
      between factor V Leiden and hyperhomocysteinemia [relative excess risk due to
      interaction (RERI) -1.77 (95%CI -8.61 to 5.08) and multiplicative interaction
      term 0.86 (95%CI 0.35 to 2.14)]. The case-only study also showed no interaction
      effect [0.58 (95%CI 0.29 to 1.16)]. Also the metaanalysis on factor V Leiden and
      MTHFR 677TT yielded no evidence of interaction; RERI 0.13 (95%CI -3.60 to 3.86)
      and multiplicative interaction term 1.23 (95%CI 0.72 to 2.11). Both the meta
      analyses of published studies and a large case-only study did not show evidence
      for interaction between factor V Leiden and hyperhomocysteinemia for risk of
      venous thrombosis.

PMID- 17200769
TI  - Plasminogen binds to plasmin-modulated factor Xa by Ca(2+) - and C-terminal
      lysine-dependent and -independent interactions.
AB  - Plasminogen binding to receptors involves both C-terminal lysine- dependent and 
      independent interactions. The latter are poorly understood. Our earlier work
      demonstrated a novel Ca (2+) -enhanced bivalent interaction between plasmin
      cleaved FXa (FXa33/13) and plasminogen truncated at Lys78 (Lys-Pg). Here we
      hypothesized that the effects of Ca (2+) may enable dissection of the C-terminal
      lysine-dependent and -independent interactions. To evaluate the role of the Glu
      plasminogen (Glu-Pg) amino acids 1 - 77, binding of FXa33/13 to immobilized Glu
      Pg was compared to Lys-Pg by surface plasmon resonance. Under identical
      conditions, approximately half the amount of FXa33/13 bound to Glu-Pg. The
      simplest fit of data suggested a 2:1 plasminogen:FXa33/13 stoichiometry for both,
      which were proportionately enhanced by Ca (2+) . Only Lys-Pg demonstrated
      significant Ca (2+) -independent binding to FXa33/13. In the presence of Ca (2+)
      , weak C-terminal lysine-independent binding could be detected, but only for Glu
      Pg. The elastase-generated plasminogen fragment encompassing the angiostatin-like
      kringle domains 1 to 3 (K1 - 3) inhibited binding of FXa33/13 to Lys-Pg, whereas
      fragments corresponding to kringle 4- and kringle 5-protease domain had no
      effect. Immobilized K1 - 3 binding to FXa33/13 had both Ca (2+) -dependent and 
      independent components. The principal K (d) for the interaction was 10-fold
      higher than Lys-Pg. In the presence of Ca (2+) , eACA inhibited FXa33/13 binding
      to K1 - 3 by 30%, but eliminated binding in the absence of Ca (2+) . These
      studies suggest that Ca (2+) -dependent and -independent binding of Lys-Pg to
      FXa33/13 are C-terminal lysine-dependent. The N-terminal 1 - 77 amino acids of
      Glu-Pg confer significant C-terminal lysine-independent binding, which may play a
      role during the initiating stages of plasminogen activation.

PMID- 17200770
TI  - A novel inhibitor of activated thrombin-activatable fibrinolysis inhibitor
      (TAFIa) - part I: pharmacological characterization.
AB  - We have discovered a novel small-molecule (3-phosphinoylpropionic acid) inhibitor
      of activated thrombin activatable fibrinolysis inhibitor (TAFIa), BX 528, which
      had an IC (50) of 2 nM in an enzymatic assay and 50 nM in an in-vitro clot lysis
      assay, with 3,500- to 35,000-fold selectivity against other carboxypeptidases,
      such as CPN, CPZ and CPD, and 5- and 12-fold selectivity against CPE (CPH) and
      CPB, respectively. At 10 micro M, BX 528 had no significant activity (<50%
      inhibition or antagonism) in a panel of 137 enzymes and receptors. It had no
      effects on blood coagulation and platelet aggregation up to 300 and 10 micro M,
      respectively. The plasma half-life following intravenous administration was 0.85
      hours in rats and 4.5 hours in dogs. No significant metabolism was detected in
      human, dog or rabbit hepatic microsomes, and no significant inhibition of
      cytochrome P450 3A4 and 2D6 up to 30 micro M. No cytotoxic or cell proliferative
      effects were found in three hepatic and renal cell lines up to 300 micro M and no
      mutagenic activity was seen in the Ames II screen. There were no significant
      hemodynamic effects in rats and dogs up to 100 and 30 mg/kg with peak plasma drug
      concentrations of approximately 1,000 and 300 micro M, respectively. In an in
      vivo complement activation model in guinea pigs, BX 528 showed minimal inhibition
      of plasma CPN activity up to 60 mg/kg with peak plasma concentrations up to 250
      micro M. Thus, these data demonstrate that BX 528 is a novel, potent, selective
      and safe TAFIa inhibitor.

PMID- 17200771
TI  - A novel inhibitor of activated thrombin activatable fibrinolysis inhibitor
      (TAFIa) - part II: enhancement of both exogenous and endogenous fibrinolysis in
      animal models of thrombosis.
AB  - We have discovered a novel small-molecule TAFIa inhibitor, BX 528, which is
      potent, highly selective against other carboxypeptidases and safe. The present
      study was to determine if BX 528 can enhance exogenous and endogenous
      thrombolysis in four different animal models. In the first three models, a
      thrombus was induced by FeCl (2) (dogs) or laser (rats) injury of the femoral
      artery, or formed ex vivo and implanted in the jugular vein in rabbits. A low
      dose of exogenous t-PA was given to induce a low-level thrombolysis on an
      established thrombus. Co-treatment with BX 528 further enhanced the thrombolytic
      effects induced by the exogenous t-PA and, thus, reduced thrombosis in all three
      animal models. In a second rat model, fibrin deposition in the lungs was induced
      by batroxobin, which was spontaneously resolved in 30 minutes due to the
      activation of endogenous fibrinolysis. Pre-treatment with lipopolysaccharide
      (LPS) attenuated this spontaneous fibrinolysis. Co-treatment with 10 mg/kg BX 528
      prevented the LPS-induced attenuation of endogenous fibrinolysis. Thus, these
      studies demonstrated that inhibition of TAFIa by BX 528, our newly discovered
      small-molecule TAFIa inhibitor, enhanced both the exogenous (induced by a low
      dose of t-PA) and endogenous (LPS-induced resistance) thrombolysis without
      increasing the bleeding risk in four different animal models of thrombosis in
      different species (rat, dog and rabbit) employing different thrombogenic stimuli
      (FeCl (2) , laser, ex vivo and batroxobin) to induce thrombus formation in
      different tissues (artery, vein and lung microcirculation).

PMID- 17200772
TI  - Polymorphism A36G of the tumor necrosis factor receptor 1 gene is associated with
      PAI-1 levels in obese women.
AB  - The tumor necrosis factor (TNF) pathway may be implicated in etiopathogenesis of
      PAI-1 overexpression during obesity. The aim of this study was to investigate the
      influence of polymorphism A36G of the TNF receptor 1 (TNFRSF1A +36A/G) on plasma
      concentrations of PAI-1 in 163 obese (31 with the metabolic syndrome, MetS) and
      150 lean, healthy women. Genotypic and allele frequencies did not significantly
      differ between obese and lean subjects. TNFRSF1A genotypes were significantly
      associated with sTNFR1 plasma levels in obese women only (p < 0.01); TNFRSF1A
      +36G/G obese carriers exhibited higher sTNFR1 and PAI-1 levels than A carriers (p
      < 0.01 and p < 0.05, respectively). In obese women, the presence of the MetS
      significantly potentiated the elevation of sTNFR1 and PAI-1 levels observed in
      the TNFRSF1A + 36G/G carriers. Our results suggest that association between
      TNFRSF1A +36G/G genotype and the MetS renders obese women more prone to
      activation of the TNF pathway reflected by high circulating sTNFR1 and PAI-1
      levels.

PMID- 17200773
TI  - Proteomic discovery of 21 proteins expressed in human plasma-derived but not
      platelet-derived microparticles.
AB  - Microparticles (MPs) are small membrane vesicles generated by essentially all
      cell types. In the plasma, most MPs are derived from platelets, but those from
      other sources, particularly leukocytes (macrophages, lymphocytes, and
      neutrophils), endothelial cells, and even smooth muscle cells can be detected and
      appear to play an important role in normal physiology and various diseases. In
      previous work we analyzed the proteome of MPs generated from isolated platelets
      (platelet MPs). Here, we report on a comparative analysis of microparticles
      isolated from plasma (plasma MPs) versus platelet MP using two complementary
      methods of comparative analysis. The first method, spectral count analysis,
      yielded 21 proteins detected in plasma MPs (with a total spectral count of 10 or
      greater) that were essentially absent in platelet MPs (with a total spectral
      count of 1 or 0). An additional two proteins (von Willebrand Factor, albumin)
      were present in both types of MPs but enriched in the plasma MPs. The second
      method, isotope-coded affinity tag (ICAT) labeling of proteins, supported the
      spectral count results for the more abundant proteins and provided better
      relative quantitation of differentially expressed proteins. Proteins present only
      in the plasma MPs include several associated with apoptosis (CD5-like antigen,
      galectin 3 binding protein, several complement components), iron transport
      (transferrin, transferrin receptor, haptoglobin), immune response (complement
      components, immunoglobulin J and kappa chains), and the coagulation process
      (protein S, coagulation factor VIII).

PMID- 17200774
TI  - Danaparoid sodium reduces ischemia/reperfusion-induced liver injury in rats by
      attenuating inflammatory responses.
AB  - This study was undertaken to examine the mechanism by which danaparoid sodium
      (DS), a heparinoid that contains mainly heparan sulfate, prevents reperfusion
      induced hepatic damage in a rat model of ischemia/reperfusion (I/R)-induced liver
      injury. Administration of DS significantly reduced liver injury and inhibited the
      decrease in hepatic tissue blood flow in rats. DS attenuated hepatic I/R-induced
      increases in hepatic tissue levels of tumor necrosis factor (TNF) and
      myeloperoxidase (MPO) in vivo. In contrast, neither monocytic TNF production nor
      neutrophil activation was inhibited by DS in vitro. DS enhanced I/R-induced
      increases in levels of calcitonin-gene related peptide (CGRP), a neuropeptide
      released from sensory neurons, and of 6-ketoprostaglandin (PG) F (1a) , a stable
      metabolite of PGI (2) , in liver tissues. The therapeutic effects of DS were not
      seen in animals pretreated with capsazepine, an inhibitor of sensory neuron
      activation. The distribution of heparan sulfate in the perivascular area was
      significantly increased by DS administration in this rat model. DS significantly
      increased CGRP release from isolated rat dorsal root ganglion neurons (DRG) in
      vitro, while DX-9065a, a selective inhibitor of activated factor X, did not. DS
      enhanced anandamide-induced CGRP release from DRG in vitro. These observations
      strongly suggested that DS might reduce I/R-induced liver injury in rats by
      attenuating inflammatory responses. These therapeutic effects of DS might be at
      least partly explained by its enhancement of sensory neuron activation, leading
      to the increase the endothelial production of PGI (2) .

PMID- 17200775
TI  - Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in
      endothelial cells: a novel antioxidative mechanism.
AB  - Lipoxins and their aspirin-triggered carbon-15 epimers have emerged as mediators
      of key events in endogenous anti-inflammation and resolution. However, the
      implication of these novel lipid mediators on cardiovascular diseases such as
      hypertension, atherosclerosis, and heart failure has not been investigated. One
      of the major features shared by these pathological conditions is the increased
      production of reactive oxygen species (ROS) generated by vascular NAD(P)H oxidase
      activation. In this study, we have examined whether an aspirin-triggered lipoxin
      A (4) analog (ATL-1) modulates ROS generation in endothelial cells (EC). Pre
      treatment of EC with ATL-1 (1 - 100 nM) completely blocked ROS production
      triggered by different agents, as assessed by dihydrorhodamine 123 and
      hydroethidine. Furthermore, ATL-1 inhibited the phosphorylation and translocation
      of the cytosplamic NAD(P)H oxidase subunit p47 (phox) to the cell membrane as
      well as NAD(P)H oxidase activity. Western blot and immunofluorescence microscopy
      analyses showed that ATL-1 (100 nM) impaired the redox-sensitive activation of
      the transcriptional factor NF- kappaB, a critical step in several events
      associated to vascular pathologies. These results demonstrate that ATL-1
      suppresses NAD(P)H oxidase-mediated ROS generation in EC, strongly indicating
      that lipoxins may play a protective role against the development and progression
      of cardiovascular diseases.

PMID- 17200776
TI  - Impaired pericyte recruitment and abnormal retinal angiogenesis as a result of
      angiopoietin-2 overexpression.
AB  - Angiopoietin-2 (Ang2) is among the relevant growth factors induced by hypoxia and
      plays an important role in the initiation of retinal neovascularizations. Ang2 is
      also involved in incipient diabetic retinopathy, as it may cause pericyte loss.
      To investigate the impact of Ang2 on developmental and hypoxia-induced
      angiogenesis, we used a transgenic mouse line overexpressing human Ang2 in the
      mouse retina. Transgenic mice displayed a reduced coverage of capillaries with
      pericytes (-14%; p < 0.01) and a 46% increase of vascular density of the
      capillary network at postnatal day 10 compared to wild type mice. In the model of
      oxygen-induced retinopathy (OIR), Ang2 overexpression resulted in enhanced
      preretinal (+103%) and intraretinal neovascularization (+29%). Newly formed
      intraretinal vessels in OIR were also pericyte-deficient (-26%; p < 0.01). The
      total expression of Ang2 in transgenic mice was seven-fold, compared with wild
      type controls. Ang2 modulated expression of genes encoding VEGF (+65%) and Ang1
      (+79%) in transgenic animals. These data suggest that Ang2 is involved in
      pericyte recruitment, and modulates intraretinal, and preretinal vessel formation
      in the eye under physiological and pathological conditions.

PMID- 17200777
TI  - Inhibition of clot formation process by treatment with the low-molecular-weight
      heparin nadroparin in patients with carotid artery disease undergoing angioplasty
      and stenting. A thromboelastography study on whole blood.
AB  - Low-molecular-weight heparins (LMWHs) have become the corner stone of
      antithrombotic treatment but their administration protocol needs to be optimized
      for certain groups of patients. In this paper, we studied the influence of
      nadroparin treatment on clot formation process assessed by thromboelastography in
      patients with carotid artery disease undergoing angioplasty and stenting.
      Standard thromboelastography assays (in-TEM and ex-TEM) and minimal TF-triggered
      thromboelastography assay in citrated whole blood were performed in normal
      volunteers (n = 20), in patients with carotid artery disease receiving only
      antiplatelet treatment (n = 30), and in patients undergoing angioplasty receiving
      nadroparin 5750 anti-Xa IU s.c. twice daily (n = 60). Blood samples were
      collected four hours after a second injection of nadroparin. In a subgroup of
      LMWH-patients (n = 18) blood samples were also obtained prior to first injection
      of LMWH. Antiplatelet treatment had no effect on any parameter of the
      thromboelastographic pattern. Nadroparin treatment resulted in significant
      prolongation of clotting time (CT) and clot formation time (CFT) and
      significantly reduced a -angle in minimal TF-triggered thromboelastography and 30
      - 38% of nadroparin treated patients had thromboelastographic parameters beyond
      the normal maximum limit. In-TEM test revealed a significant prolongation of
      clotting time while ex-TEM was not modified, and 20 to 30% of the patients had
      thromboelastographic parameters beyond the normal maximum limit. Anti factor-Xa
      activity in platelet-poor plasma (PPP) was also measured, and statistical
      analysis showed that prolongation of CFT of minimal TF-triggered TEM was
      significantly correlated to the levels of anti-Xa activity in patients ' plasma
      (p = 0.04; r (2) = 0.7). There was no statistical correlation for any other
      parameter in all tests. In conclusion, the present study shows that nadroparin
      treatment in patients with carotid artery disease undergoing endovascular
      procedures induces significant modification of the thrombus kinetics assessed by
      minimal TF-triggered whole blood thromboelastography. The clinical relevance of
      these findings has to be evaluated in future studies.

PMID- 17200778
TI  - Tissue factor-positive microparticles: cellular origin and association with
      coagulation activation in patients with colorectal cancer.
AB  - The pathogenesis of hypercoagulability in cancer is not entirely understood. We
      hypothesized that in cancer patients circulating tissue factor-positive
      microparticles (TF (+) MPs) are increased and associated with hemostatic system
      activation. In 20 patients with advanced colorectal cancer and in 20 age- and sex
      matched controls, number and cellular origin of TF (+) MPs were determined in
      plasma by flow cytometry. D-dimer was determined as an indicator of hemostatic
      system activation. Compared to controls, the median (interquartile range) number
      of TF (+) MPs was two-fold higher in cancer patients: 25.9 (15.4 - 42.0) x 10 (3)
      /ml plasma versus 13.1 (11.9 - 19.7) x 10 (3) /ml plasma, p = 0.007. This was
      mainly due to a higher amount of TF (+) MPs from platelets (13.4 [5.0 - 17.4] x
      10 (3) /ml plasma vs. 5.8 [4.5 - 7.5] x 10 (3) /ml plasma, p = 0.017). TF (+) MPs
      correlated with D-dimer ( ? = 0.48, p = 0.002). High levels of TF (+) MPs in
      cancer patients and their correlation with D-dimer suggest that TF (+) MPs might
      be involved in hemostasis activation in cancer patients.

PMID- 17200779
TI  - Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic
      mouse model via recovery of hypercoagulability.
AB  - Diabetic nephropathy, a major complication of diabetes mellitus that leads to
      mortality, has been shown to involve a dysregulation of the coagulation system.
      Annexin-2, a co-receptor for plasminogen and tissue plasminogen activator on
      endothelial cells, is one of the molecules required to maintain the
      antithrombogenic properties of endothelial cells. Previously, we showed that
      recombinant annexin-2 protein (rAN II) modulated impaired fibrinolytic activity
      in the carotid arteries of rats. In the present study, to investigate its
      protective effects against diabetic nephropathy, rAN II was administered to KK-Ay
      mice, a murine model of type 2 diabetes, for eight weeks, and albuminuria, kidney
      size, and histological glomerular lesions were investigated. The mean weight of
      kidneys from KK-Ay mice treated with rAN II was significantly less than that of
      those treated with PBS (control) (p < 0.02). Furthermore, the level of
      albuminuria observed in rAN II-treated KK-Ay mice was significantly less than
      that of the control group (rAN II, 0.90+/-0.12 microg/day; PBS, 1.55+/-0.31
      microg/day; p < 0.01); also, the area of diffuse glomerular lesions was
      significantly smaller (rAN II, 41.51+/-4.54%; PBS, 81.81+/-8.10%; p < 0.01).
      Bleeding time, prothrombin time (PT), and active partial thromboplastin time
      (APTT) did not significantly differ between the two groups. Our results suggest
      that rAN II may inhibit the progression of diabetic nephropathy in KK-Ay mice
      without influencing the coagulation system, indicating that annexin-2 may be
      considered as a possible new therapeutic tool for patients with diabetic
      nephropathy.

PMID- 17200780
TI  - Immunization of LDL receptor-deficient mice with beta2-glycoprotein 1 or human
      serum albumin induces a more inflammatory phenotype in atherosclerotic plaques.
AB  - Antiphospholipid antibodies are a risk factor for venous and arterial thrombosis
      and may contribute to the development of atherosclerosis.The aim of this study
      was to investigate whether antibodies to human beta2-glycoprotein 1 (beta2GP1),
      as a model of antiphospholipid antibodies, modify the phenotype of
      atherosclerotic lesions. LDL receptor-deficient mice were immunized with human
      beta2GP1, human serum albumin (HSA), or not immunized, and fed a high-cholesterol
      diet for 14 weeks. Some mice also received pravastatin. Immunization with human
      beta2GP1 or HSA resulted in formation of autoantibodies recognizing murine
      beta2GP1 or murine albumin, respectively. We quantified atherosclerotic lesion
      development and mRNA levels of inflammation associated proteins in the thoraco
      abdominal aorta as well as lesion development,cellular composition and collagen
      content in the aortic roots. Immunization with beta2GP1 or HSA had no effect on
      lesion size,but modified the expression in plaque areas of several inflammation
      associated proteins. Expression of matrix metalloproteinase-9, tissue factor,
      interferon-gamma and CD25 was highest in the thoraco-abdominal aorta of beta2GP1
      immunized mice, lowest in non-immunized mice and intermediate in HSA-immunized
      animals. Immunization with beta2GP1, but not HSA, resulted in a lower smooth
      muscle cell and collagen content of lesions in aortic roots. Statin treatment
      partially reversed the effects of beta2GP1 immunization. We conclude that
      immunization with beta2GP1, and to a lesser extent with HSA, leads to
      modifications in the cellular and protein composition of atherosclerotic plaques,
      which are associated with a more inflammatory phenotype. Statin treatment
      partially prevents these changes.

PMID- 17200781
TI  - Design and characterization of dipetacompinR10H, a dipetalogastin II-derived,
      classical competitive thrombin inhibitor.
AB  - The design of small chimeric thrombin inhibitors based on the structure of
      dipetalogastin II has been previously described. These proteins are effective
      inhibitors of thrombin showing slow binding or slow, tight-binding kinetics. We
      report here about dipetacompinR10H, a new dipetalogastin II-derived chimeric
      thrombin inhibitor, which exhibits classical competitive kinetics. The
      dissociation constant K (i) of dipetacompinR10H was determined to be 17.1 +/- 0.8
      pM. In various coagulation assays it showed a comparable anticoagulant activity
      like r-hirudin and r-dipetalogastin II. DipetacompinR10H ' s inhibition of
      thrombin was specific, since no inhibition of other serine proteases like factor
      Xa, plasmin, trypsin or chymotrypsin has been observed.

PMID- 17200782
TI  - Simple and safe exclusion of pulmonary embolism in outpatients using quantitative
      D-dimer and Wells' simplified decision rule.
AB  - A safe and effective management strategy is pivotal in excluding pulmonary
      embolism (PE). The combination of Wells' simplified dichotomous clinical decision
      rule and D-dimer test is non-invasive and could be highly efficient, though its
      safety has not been widely studied. We evaluated safety and efficiency of this
      combination in excluding PE. Wells clinical decision rule was performed in 941
      consecutive patients with suspected PE and, if patients had a score <or=4.0
      points, a VIDAS D-dimer test followed. Patients with a normal D-dimer
      concentration had no further tests, PE was considered excluded, and patients did
      not receive anticoagulant treatment. Patients, in whom PE was excluded, were
      followed up for three months. Four hundred fifty patients (51.2%) had a clinical
      decision score =4.0 points and a normal D-dimer concentration. In 45 of these
      patients, during the initial diagnostic period additional objective testing,
      although not indicated, was performed, and PE was established in two patients.
      During three months of follow up no venous thromboembolic events (VTE) occurred.
      Therefore, the overall VTE failure rate was two of 450 (0.4% [95%CI 0-1.1]); the
      overall prevalence of PE was 12.3%. The diagnostic protocol could be completed
      and allowed a decision to be made in 90% of the study patients. This study has
      prospectively established the safety of a combination of a dichotomized clinical
      decision rule and D-dimer test in ruling out PE. The strategy proved highly
      efficient, since more than 50% of patients could be managed without the need for
      more invasive and expensive tests.

PMID- 17200783
TI  - The importance of tissue factor source in the management of Factor VII
      deficiency.

PMID- 17200784
TI  - Coexistence of three genetic risk factors in a Spanish thrombophilic family:
      Factor V Leiden, prothrombin 20210 and a new type I antithrombin deficiency.

PMID- 17200785
TI  - Formation of mixed platelet-PMN leukocyte aggregates in the platelet function
      analyzer (PFA-100) device.

PMID- 17200786
TI  - IL-4 modulates tissue factor expression by human B lymphocytes in response to
      phorbol myristate acetate.

PMID- 17200787
TI  - The R2464C missense mutation in the von Willebrand factor gene causes a novel
      abnormality of multimer electrophoretic mobility and falls into the subgroup of
      type 2 von Willebrand disease 'unclassified'.

PMID- 17200788
TI  - Low soluble thrombomodulin activity and antigen is associated with a family
      history of heart disease while a high level is associated with a personal history
      of heart disease in type 2 diabetes.

PMID- 17200789
TI  - Protein C deficiency screening using a thrombin-generation assay.

PMID- 17200790
TI  - A further note on thrombosis in patients with homozygous beta thalassemia.

PMID- 17200791
TI  - Consequences of prenatal toxin exposure for mental health in children and
      adolescents: a systematic review.
AB  - Drug use during pregnancy is common and the developing foetus may be exposed to a
      range of environmental toxins that have long-term consequences for
      neurodevelopment. We conducted a systematic review of the literature to explore
      the results of longitudinal cohort studies that have examined this question. Out
      of 2,977 abstracts identified, 7 previous systematic reviews and 95 original
      articles met further selection criteria. These mostly addressed the
      neurodevelopmental effects of exposure to lead, polychlorinated biphenyls,
      mercury, cocaine, alcohol, marijuana, cigarettes and antidepressants. Radiation,
      opiates, steroids, amphetamines and caffeine have received much less attention.
      Findings are difficult to interpret because risk factors tend to cluster together
      and interact. However, some findings are consistent. Lead and PCB's have a
      general effect on brain development, whilst marijuana and alcohol appear to have
      long-term effects specifically on attentional skills. The effects of alcohol
      increase with maternal age and binge drinking is more important than average
      intake. The effects of cocaine diminish with age and are largely mediated through
      psychosocial factors, whilst the relation between smoking and later delinquency
      is largely mediated by genetically inherited factors. Exposure to toxins during
      pregnancy may constitute an important but relatively unacknowledged cause of
      child psychiatric morbidity.

PMID- 17200792
TI  - Exposure to HIV in Brazilian adolescents: the impact of psychiatric
      symptomatology.
AB  - OBJECTIVES: To examine associations between psychiatric symptomatology and HIV
      positive status in adolescents who sought HIV testing at a public health center
      in Brazil. METHOD: In a cross-sectional study, 388 adolescents assessed for their
      HIV status were also evaluated for psychiatric symptomatology using the Symptom
      Checklist-90-R (SCL-90-R). The impact of potential confounding variables such as
      risk behaviors was ascertained using the Brazilian version of the Risk Assessment
      Battery (RAB). RESULTS: Overall seropositivity rate was 6.2%. Seropositives had
      significantly higher scores in all dimensions of psychiatric symptomatology in
      the SCL-90-R (P < 0.05 and effect sizes > 0.5 in all dimensions). In multiple
      analyses, with the inclusion of 3 composite variables (sex-risk, drug-risk, and
      psychiatric symptomatology), only psychiatric symptoms were associated with
      positive HIV status (OR = 1.88, CI95% = 1.06-3.34; P = 0.032). CONCLUSIONS: Our
      findings suggest that amongst young people asking for HIV testing in Brazil,
      seropositivity is associated with psychological symptoms and that screening for
      the latter would therefore be appropriate in this context.

PMID- 17200793
TI  - Childhood depression: a place for psychotherapy. An outcome study comparing
      individual psychodynamic psychotherapy and family therapy.
AB  - BACKGROUND: Although considered clinically effective, there is little systematic
      research confirming the use of Individual Psychodynamic Psychotherapy or Family
      Therapy as treatments for depression in children and young adolescents. AIMS: A
      clinical trial assessed the effectiveness of these two forms of psychotherapy in
      treating moderate and severe depression in this age group. METHODS: A randomised
      control trial was conducted with 72 patients aged 9-15 years allocated to one of
      two treatment groups. RESULTS: Significant reductions in disorder rates were seen
      for both Individual Therapy and Family Therapy. A total of 74.3% of cases were no
      longer clinically depressed following Individual Therapy and 75.7% of cases were
      no longer clinically depressed following Family Therapy. This included cases of
      Dysthymia and "Double Depression" (co-existing Major Depressive Disorder and
      Dysthymia). There was also an overall reduction in co-morbid conditions across
      the study. The changes in both treatment groups were persistent and there was
      ongoing improvement. At follow up six months after treatment had ended, 100% of
      cases in the Individual Therapy group, and 81% of cases in the Family Therapy
      group were no longer clinically depressed. CONCLUSIONS: This study provides
      evidence supporting the use of focused forms of both Individual Psychodynamic
      Therapy and Family Therapy for moderate to severe depression in children and
      young adolescents.

PMID- 17200794
TI  - Retinal vasculitis and vitreous hemorrhage associated with mixed connective
      tissue disease: retinal vasculitis in MCTD.
AB  - BACKGROUND: Retinal vasculitis associated with mixed connective tissue disease
      (MCTD) has rarely been reported in the literature. We describe a rare case of a
      patient with serious retinal vasculopathy and vitreous hemorrhages associated
      with MCTD. CASE: A 53-year-old woman with MCTD who has had recurrent retinal
      vasculitis and vitreous hemorrhage in the right eye since 2000 presented with
      blurred vision in the right eye in April 2003. The best-corrected visual acuity
      was counting finger in the right eye. The patient was clinically diagnosed as
      having retinal and vitreous hemorrhages and retinal infarction. Prednisolone was
      administered orally in a daily dose of 20 mg. RESULTS: The retinal and vitreous
      hemorrhage improved in 7 days. The best-corrected visual acuity improved to more
      than 20/20 on prednisolone alone. CONCLUSION: MCTD can be associated with retinal
      vasculitis and vitreous hemorrhage which in our case responded well to systematic
      low doses of corticosteroid therapy.

PMID- 17200795
TI  - Prevalence and causes of blindness and visual impairment among school children in
      south-western Nigeria.
AB  - The aim of the study was to assess the prevalence and identify the causes of
      blindness and visual impairment in school children of Ilesa-East Local Government
      Area of Osun State, Nigeria. A total of 1144 school children in primary and
      secondary schools were selected using a 2-stage random sampling method and
      examined to determine the prevalence and causes of blindness and visual
      impairment. A total of 17 (1.48%) children were blind or visually impaired. These
      comprised of 11 (0.96%) children who were visually impaired and 4 (0.3%) who were
      severely visually impaired. Only 2 (0.15%) school children were blind. The causes
      of visual impairment were refractive error 10 (0.87%) and immature cataract 1
      (0.08%), causes of severe visual impairment included corneal opacities 2 (0.2%),
      amblyopia leading to squint 1 (0.08%) and 1 cataract 1 (0.08%). The causes of
      blindness in school children were corneal scars presumed to be due to vitamin A
      deficiency 1 (0.08%) and keratoconus 1 (0.08%). Causes of blindness and visual
      impairment in children attending regular schools in Nigeria were treatable.
      Prevention, early recognition and prompt treatment of these diseases by regular
      screening of school children would definitely reduce unnecessary visual handicap
      in Nigerian school children so that they can attain their full potential in the
      course of their education. Also, information from this study is relevant for the
      purpose of planning eye care programmes for the prevention of blindness in
      Nigerian school children. This will go a long way in the prevention of
      unnecessary blindness and visual impairment in school children.

PMID- 17200796
TI  - Astrobiology and biological chirality.
AB  - The emerging discipline of astrobiology could gain valuable support from research
      dealing with the problems of biological chirality. The most profitable fields of
      common interest are: (a) living organisms under extraterrestrial conditions, (b)
      extraterrestrial signatures of life and (c) origin(s) of biological chirality.
      These areas of complementary and overlapping fields are analysed on the basis of
      selected references.

PMID- 17200797
TI  - Effect of hypoxia on the binding and subcellular distribution of iron regulatory
      proteins.
AB  - Iron regulatory proteins 1 and 2 (IRP1, IRP2) are key determinants of uptake and
      storage of iron by the liver, and are responsive to oxidative stress and hypoxia
      potentially at the level of both protein concentration and mRNA-binding activity.
      We examined the effect of hypoxia (1% O(2)) on IRP1 and IRP2 levels (Western
      blots) and mRNA-binding activity (gel shift assays) in human hepatoma HepG2
      cells, and compared them with HEK 293 cells, a renal cell line known to respond
      to hypoxia. Total IRP binding to an iron responsive element (IRE) mRNA probe was
      increased several fold by hypoxia in HEK 293 cells, maximally at 4-8 h. An
      earlier and more modest increase (1.5- to 2-fold, peaking at 2 h and then
      declining) was seen in HepG2 cells. In both cell lines, IRP1 made a greater
      contribution to IRE-binding activity than IRP2. IRP1 protein levels were
      increased slightly by hypoxia in HEK 293 but not in HepG2 cells. IRP1 was
      distributed between cytosolic and membrane-bound fractions, and in both cells
      hypoxia increased both the amount and IRE-binding activity of the membrane
      associated IRP1 fraction. Further density gradient fractionation of HepG2
      membranes revealed that hypoxia caused an increase in total membrane IRP1, with a
      shift in the membrane-bound fraction from Golgi to an endoplasmic reticulum (ER)
      enriched fraction. Translocation of IRP to the ER has previously been shown to
      stabilize transferrin receptor mRNA, thus increasing iron availability to the
      cell. Iron depletion with deferoxamine also caused an increase in ER-associated
      IRP1. Phorbol ester caused serine phosphorylation of IRP1 and increased its
      association with the ER. The calcium ionophore ionomycin likewise increased ER
      associated IRP1, without affecting total IRE-binding activity. We conclude that
      IRP1 is translocated to the ER by multiple signals in HepG2 cells, including
      hypoxia, thereby facilitating its role in regulation of hepatic gene expression.

PMID- 17200799
TI  - Design and feasibility of a randomized behavioral intervention to reduce
      distributive injection risk and improve health-care access among hepatitis C
      virus positive injection drug users: the Study to Reduce Intravenous Exposures
      (STRIVE).
AB  - Hepatitis C virus (HCV) is hyperendemic among injection drug users (IDUs).
      However, few scientifically proven interventions to prevent secondary
      transmission of HCV from infected IDUs to others exist. This report describes the
      design, feasibility, and baseline characteristics of participants enrolled in the
      Study to Reduce Intravenous Exposure (STRIVE). STRIVE was a multisite, randomized
      control trial to test a behavioral intervention developed to reduce distribution
      of used injection equipment (needles, cookers, cottons, and rinse water) and
      increase health-care utilization among antibody HCV (anti-HCV) positive IDUs.
      STRIVE enrolled anti-HCV positive IDU in Baltimore, New York City, and Seattle;
      participants completed behavioral assessments and venipuncture for HIV, HCV-RNA,
      and liver function tests (LFTs) and were randomized to attend either a six
      session, small-group, peer-mentoring intervention workshop or a time-matched,
      attention-control condition. Follow-up visits were conducted at 3 and 6 months.
      At baseline, of the 630 HCV-positive IDUs enrolled (mean age of 26 years, 60%
      white, 76% male), 55% reported distributive needle sharing, whereas 74, 69, and
      69% reported sharing cookers, cottons, and rinse water, respectively. Health-care
      access was low, with 41% reporting an emergency room as their main source of
      medical care. Among those enrolled, 66% (418/630) were randomized: 53% (222/418)
      and 47% (196/418) to the intervention and control conditions, respectively.
      Follow-up rates were 70 and 73% for the 3- and 6-month visits, respectively. As
      distributive sharing of used injection equipment was common while reports of
      receiving HCV care were low, these findings indicate an urgent need for HCV
      related interventions with IDUs and demonstrate the acceptability and feasibility
      to do so.

PMID- 17200798
TI  - Impact of the 2004 influenza vaccine shortage on patients from inner city health
      centers.
AB  - In the fall of 2004, the FDA and British authorities suspended the license of one
      of only two manufacturers that provided the US supply of inactivated influenza
      vaccine. With a 50% reduction in supply, a severe vaccine shortage resulted. This
      situation necessitated the development of priority groups for vaccination
      including those > or =65 years, when ordinarily, influenza vaccine is recommended
      for those > or =50 years old. A sample of patients > or =50 years old (n = 336),
      who had been seen at one of four inner-city health centers, was interviewed in
      summer 2005 using computer-assisted telephone interviewing. Associations of
      survey responses were examined for three groups: those vaccinated in the 2003
      2004 and 2004-2005 influenza seasons (n = 142), those vaccinated in 2003-2004 but
      not vaccinated in 2004-2005 because of the shortage (n = 63), and those
      unvaccinated in both seasons (n = 83). Bivariate and multivariate logistic
      regression analyses were used to determine factors significantly influencing the
      likelihood of vaccination status. A significantly larger proportion of patients
      50-64 years of age were unvaccinated due to the shortage (73%) compared to those
      who were vaccinated during both seasons (36%, P < 0.001), but there were no
      racial disparities in vaccination rates. Compared with patients who were
      vaccinated during both seasons, those who were unvaccinated due to the shortage
      were more frequently employed, self-reported their health positively, saw their
      physician less frequently, rated the US government's response to the shortage as
      "terrible," and blamed the US government for the shortage. Vaccination during the
      influenza vaccine shortage appears to have followed preferential vaccination of
      the CDC-established priority group (> or =65 years) and did not result in racial
      disparities in inner-city health centers.

PMID- 17200800
TI  - Identifying students with self-report of asthma and respiratory symptoms in an
      urban, high school setting.
AB  - Strategies for identifying urban youth with asthma have not been described for
      high school settings. African-American high school students are rarely included
      in asthma studies, despite a high risk of asthma mortality when compared to other
      age and race groups. Identification and follow-up of children with uncontrolled
      respiratory symptoms are necessary to reduce the burden of asthma morbidity and
      mortality, especially in underserved areas. We describe a process used to
      identify high school students who could benefit from intervention based on self
      report of asthma and/or respiratory symptoms, and the costs associated with
      symptom-identification. Letters announcing a survey were mailed to parents of 9th
      11th graders by an authorized vendor managing student data for the school
      district. Scan sheets with student identifiers were distributed to English
      teachers at participating schools who administered the survey during a scheduled
      class. Forms were completed by 5,967 of the 7,446 students assigned an English
      class (80% response). Although prevalence of lifetime asthma was 15.8%, about 11%
      of students met program criteria for enrollment through report of an asthma
      diagnosis and recent symptoms, medication use, or health care utilization.
      Another 9.2% met criteria by reported symptoms only. Cost of symptom
      identification was $5.23/student or $32.29/program-eligible student. There is a
      need for school-based asthma programs targeting urban adolescents, and program
      initiation will likely require identification of students with uncontrolled
      symptoms. The approach described was successfully implemented with a relatively
      high response rate. Itemized expenses are presented to facilitate modifications
      to reduce costs. This information may benefit providers, researchers, or
      administrators targeting similar populations.

PMID- 17200801
TI  - Sarcoidosis presenting as an osteolytic skull lesion: a case report and review of
      literature on skull sarcoidosis.
AB  - Bone sarcoidosis of the skull is an infrequent presentation of sarcoidosis. We
      describe a 51-year-old man who consulted due to inflammatory-appearing nodulation
      in the right supraorbital region. Images showed a solitary osteolytic lesion
      extending to soft tissues with increased scintigraphic uptake. The
      anatomopathological study revealed the presence of non-caseating epithelioid
      granulomas, compatible with sarcoidosis. Steroid treatment led to a marked
      remission of the lesion, without evidence of relapse during a follow-up period of
      1 year. The literature dealing with skull sarcoidosis is reviewed.

PMID- 17200802
TI  - Lymphomatoid granulomatosis and diffuse alveolar damage associated with
      methotrexate therapy in a patient with rheumatoid arthritis.
AB  - We report on a patient of rheumatoid arthritis (RA) who sequentially developed an
      axillary mass and a fatal interstitial pneumonia during a 2-year course of
      methotrexate (MTX) therapy. Autopsy revealed a systemic lymph node involvement
      and the diagnosis of Epstein-Barr virus (EBV)-related lymphoproliferative disease
      (LPD) with the features of lymphomatoid granulomatosis was made. The lung tissue
      specimens revealed a typical diffuse alveolar damage (DAD), and small nodules
      consisting of atypical B lymphocytes showing positive staining for EBV were
      sparsely recognized only in basal lungs. This is the first report of a RA patient
      receiving MTX therapy sequentially developing MTX-associated lymphomatoid
      granulomatosis and DAD.

PMID- 17200803
TI  - Autoinduction of RpoS biosynthesis in the biocontrol strain Pseudomonas sp. M18.
AB  - The rpoS gene from Pseudomonas sp. M18, which encodes predicted protein (an
      alternative sigma factor s, sigma(S), or sigma(38)) with 99.5% sequence identity
      with RpoS from Pseudomonas aeruginosa PAO1, was first cloned. In order to
      investigate the mechanism of rpoS expression, an rpoS null mutant, named M18S,
      was constructed with insertion of aacC1 cassette bearing a gentamycin resistance
      gene. With introduction of a plasmid containing an rpoS'-'lacZ translational
      fusion (pMERS) to wild-type strain M18 or M18S, it was first found that beta
      galactosidase activity expressed in strain M18S (pMERS) decreased to fourfold of
      that expressed in the strain M18 (pMERS). When strain M18S (pMERS) was introduced
      with another plasmid pBBS containing the wild-type rpoS gene, its beta
      galactosidase expression level was enhanced and almost restored to that in strain
      M18 (pMERS). Similarly, expression of beta-galactosidase from a chromosomal
      fusion of the promoter of the wild-type rpoS gene with lacZ (rpoS-lacZ) was
      enhanced fivefold in the presence of a plasmid with the wild-type rpoS gene. With
      these findings, it is suggested that RpoS sigma factor may be involved in
      autoinducing its own gene expression in Pseudomonas sp. M18.

PMID- 17200804
TI  - Mercury resistance in bacterial strains isolated from tailing ponds in a gold
      mining area near El Callao (Bolivar State, Venezuela).
AB  - Bacterial resistance to mercury (Hg) was investigated in strains isolated from Hg
      contaminated tailing ponds located in the gold mining area of El Callao (Bolivar
      State, Venezuela). High frequencies of resistance were detected to both inorganic
      Hg and organomercurials among these strains. A broad range of resistance levels
      was observed when determining minimal inhibitory concentrations of Hg(2+). Some
      strains were able to grow in liquid medium containing 25 muM: Hg(2+), whereas
      others grew at 300 muM: Hg(2+). Of 190 Hg-resistant strains tested, 58.2% were
      additionally shown to be resistant to ampicillin (40 mg/L), 33.3% to
      chloramphenicol (30 mg/L), 24.9% to streptomycin (30 mg/L), 23.3% to tetracycline
      (30 mg/L), and 1.6% to kanamycin (30 mg/L). Furthermore, we found that 20% of the
      Hg-resistant strains were simultaneously resistant to as many as four of these
      antibiotics, at the concentrations tested. The presence of large plasmids in
      62.9% of 53 Hg-resistant strains screened prompted us to investigate the
      horizontal transfer of resistance determinants. Mating experiments were performed
      using Escherichia coli and Pseudomonas aeruginosa as recipient strains. The
      results obtained confirmed that indigenous Hg-resistant bacteria colonizing the
      tailing ponds can effectively transfer the phenotype to potentially pathogenic
      species.

PMID- 17200805
TI  - Ethyl methanesulfonate mutagenesis-enhanced mineral phosphate solubilization by
      groundnut-associated Serratia marcescens GPS-5.
AB  - Twenty-three bacterial isolates were screened for their mineral phosphate
      solubilizing (MPS) ability on Pikovskaya and National Botanical Research
      Institute's phosphate (NBRIP) agar. The majority of the isolates exhibited a
      strong ability to solubilize hydroxyapatite in both solid and liquid media. The
      solubilization in liquid medium corresponded with a decrease in the pH of the
      medium. Serratia marcescens GPS-5, known for its biocontrol of late leaf spot in
      groundnut, emerged as the best solubilizer. S. marcescens GPS-5 was subjected to
      ethyl methanesulfonate (EMS) mutagenesis, and a total of 1700 mutants, resulting
      after 45 minutes of exposure, were screened on buffered NBRIP medium for
      alterations in MPS ability compared with that of the wild type. Seven mutants
      with increased (increased-MPS mutants) and 6 mutants with decreased (decreased
      MPS mutants) MPS ability were isolated. All seven increased-MPS mutants were
      efficient at solubilizing phosphate in both solid and liquid NBRIP medium. Among
      the increased-MPS mutants, EMS XVIII Sm-35 showed the maximum (40%) increase in
      the amount of phosphate released in liquid medium compared with wild-type S.
      marcescens GPS-5, therefore, it would be a useful microbial inoculant in
      groundnut cultivation. EMS III Sm W, a nonpigmented mutant, showed the lowest
      solubilization of phosphate among the 6 decreased-MPS mutants.

PMID- 17200808
TI  - Materials and interfaces with medicine and dentistry. Proceedings of a symposium
      held at the ASME Winter Annual Meeting. November 2003.

PMID- 17200807
TI  - Using variable rate models to identify genes under selection in sequence pairs:
      their validity and limitations for EST sequences.
AB  - Using likelihood-based variable selection models, we determined if positive
      selection was acting on 523 EST sequence pairs from two lineages of sunflower and
      lettuce. Variable rate models are generally not used for comparisons of sequence
      pairs due to the limited information and the inaccuracy of estimates of specific
      substitution rates. However, previous studies have shown that the likelihood
      ratio test (LRT) is reliable for detecting positive selection, even with low
      numbers of sequences. These analyses identified 56 genes that show a signature of
      selection, of which 75% were not identified by simpler models that average
      selection across codons. Subsequent mapping studies in sunflower show four of
      five of the positively selected genes identified by these methods mapped to
      domestication QTLs. We discuss the validity and limitations of using variable
      rate models for comparisons of sequence pairs, as well as the limitations of
      using ESTs for identification of positively selected genes.

PMID- 17200806
TI  - Patterns of group I intron presence in nuclear SSU rDNA of the Lichen family
      Parmeliaceae.
AB  - Group I introns are commonly reported within nuclear SSU ribosomal DNA of
      eukaryotic micro-organisms, especially in lichen-forming fungi. We have studied
      the primary and secondary structure of 70 new nuclear SSU rDNA group I introns of
      Parmeliaceae (Ascomycota: Lecanorales) and compared them with those available in
      databases, covering more than 60 species. The analyzed samples of Parmeliaceae
      fell into two groups, one having an intron at the 1506 site and another lacking
      this one but having another at the 1516 or 1521 position. Introns at the 1521
      position seem to be transposed from 1516 sites. Introns at the 1516 position were
      similar in structure to ones previously reported at this site and known from
      other lecanoralean fungi, while those at the 1506 position showed structural
      differences and no similar introns are known from related fungi. The study of the
      distribution of group I introns within a large monophyletic ensemble of fungi has
      revealed an unexpected correlation between intron types and ecological and
      geographical parameters. The introns at the 1516 position occurred in mainly
      arctic, boreal, and temperate lichens, while those at position 1506 were present
      in mainly tropical and subtropical to oceanic mild-temperate taxa. Further, the
      1516 introns occurred in genera with few distributed species that could represent
      older taxa, while the 1506 ones were mainly in species-rich genera that could be
      of recent speciation, as many species have wide distribution areas. The
      transition between two different environments has been accompanied by a change in
      introns gained and lost.

PMID- 17200809
TI  - A folic acid-based functionalized surface for biosensor systems.
AB  - The performance of a biosensor depends largely on its interface with the
      biological system. This interface imparts a biologically relevant function to the
      device and provides a measure of specificity towards the biological analyte of
      interest. This paper documents the choice of folic acid as the functional
      component of a cantilever sensor to recognize nasopharyngeal (KB) cancer cells. A
      conjugation chemistry protocol has been outlined to deploy folic acid onto a
      titanium-coated sensor surface using a silane linker. The presence and biological
      activity of the sensor was verified by means of an immunospecific (ELISA)
      procedure. The overall performance of the folic acid-based cantilever sensor was
      measured using cancerous KB cell-binding experiments.

PMID- 17200810
TI  - Cell/surface interactions on laser micro-textured titanium-coated silicon
      surfaces.
AB  - This paper examines the effects of nano-scale titanium coatings, and micro
      groove/micro-grid patterns on cell/surface interactions on silicon surfaces. The
      nature of the cellular attachment and adhesion to the coated/uncoated micro
      textured surfaces was elucidated by the visualization of the cells and relevant
      cytoskeletal & focal adhesion proteins through scanning electron microscopy and
      immunofluorescence staining. Increased cell spreading and proliferation rates are
      observed on surfaces with 50 nm thick Ti coatings. The micro-groove geometries
      have been shown to promote contact guidance, which leads to reduced scar tissue
      formation. In contrast, smooth surfaces result in random cell orientations and
      the increased possibility of scar tissue formation. Immunofluorescence cell
      staining experiments also reveal that the actin stress fibers are aligned along
      the groove dimensions, with discrete focal adhesions occurring along the ridges,
      within the grooves and at the ends of the cell extensions. The implications of
      the observed cell/surface interactions are discussed for possible applications of
      silicon in implantable biomedical systems.

PMID- 17200811
TI  - Membrane thickness design of implantable bio-MEMS sensors for the in-situ
      monitoring of blood flow.
AB  - This paper presents some ideas for the membrane thickness design of of
      implantable bio-micro-electro-mechanical systems (bio-MEMS) for the in situ
      monitoring of blood flow. The objective is to develop a smart wireless sensing
      unit for non-invasive early stenosis detection in heart bypass grafts. The design
      includes considerations of nonlinear material models, multiscale blood flows, and
      appropriate analyical models for data interpretation, as well as preliminary
      studies of the pressure and flow sensing concepts. The paper also examines the
      use of surface coatings for the design on biocompatibility and non-adhesion of
      blood platelets and constituents. The implications of the results are discussed
      for in vivo deployment of such sensor systems.

PMID- 17200812
TI  - Piezoelectric generators for biomedical and dental applications: effects of
      cyclic loading.
AB  - This paper presents the results of a study of the effect of cyclic loading
      parameters on the performance of piezo crystals. The output power of the crystals
      was observed to increase with parameters such as the cyclic frequency and the
      dynamic load range. However, the output power also decreased with increasing mean
      load. The efficiency of the crystal was calculated based on the mechanical energy
      applied to the piezo crystal. The ratio of the electrical output to mechanical
      energy input was taken as the efficiency of the crystal. This ratio was seen to
      increase with the cycling frequency, and also with the dynamic load range.
      However, increasing mean load caused the efficiency to drop significantly. The
      implications of the results are discussed for possible applications implanted
      bioMEMS and microelectronics systems.

PMID- 17200813
TI  - Engineering long term clinical success of advanced ceramic prostheses.
AB  - Biocompatability and, in some applications, esthetics make all-ceramic prostheses
      compelling choices but despite significant improvements in materials properties
      and toughening mechanisms, these still have significant failure rates. Factors
      that contribute to the degradation in strength and survival include material
      selection and prosthesis design which set the upper limit for performance.
      However, fabrication operations introduce damage that can be exacerbated by
      environmental conditions and clinical function. Using all-ceramic dental crowns
      as an example, experimentally derived models provide insight into the
      relationships between materials properties and initial critical loads to failure.
      Analysis of fabrication operations suggests strategies to minimize damage.
      Environmental conditions can create viscoplastic flow of supporting components
      which can contribute additional stress within the prosthesis. Fatigue is a
      particularly challenging problem, not only providing the energy to propagate
      existing damage but, when combined with the wet environment, can create new
      damage modes. While much is known, the influence of these new damage modes has
      not been completely elucidated. The role of complex prosthesis geometry and its
      interaction with other factors on damage initiation and propagation has yet to be
      well characterized.

PMID- 17200814
TI  - Bioinspired design of dental multilayers.
AB  - This paper considers the use of bioinspired functionally graded structures in the
      design of dental multi-layers that are more resistant to sub-surface crack
      nucleation. Unlike existing dental crown restorations that give rise to high
      stress concentration, the functionally graded layers (between crown materials and
      the joins that attach them to dentin) are shown to promote significant reductions
      in stress and improvements in the critical crack size. Special inspiration is
      drawn from the low stress concentrations associated with the graded distributions
      in the dentin-enamel-junction (DEJ). The implications of such functionally graded
      structures are also discussed for the design of dental restorations.

PMID- 17200815
TI  - Creep induced rate effects on radial cracks in multilayered structures.
AB  - This paper considers foundation and epoxy creep induced loading rate effects on
      radial cracks in multilayered structures. These include top layers of glass or
      silicon that are bonded to polycarbonate foundations with epoxy. The creep
      properties of the epoxy join and the polycarbonate foundation are determined
      using compression experiments and spring-dashpot models. The measured creep
      parameters are then incorporated into an analytical mechanics model, and finite
      element simulations are used to predict the effects of creep on the critical
      loads for radial cracking at different loading rates. The models suggest that the
      combined effects of creep and slow crack growth must be considered in the
      predictions of the critical loads required for radial cracking in the systems
      containing glass top layers. Since slow crack growth does not occur in silicon,
      the model considering the creep effect is used to predict the critical loads for
      radial cracking in the systems containing silicon top layers. In both of the
      structures, analytical solutions are obtained for bi-layer structures and finite
      element simulations are used for tri-layer structures. Our results show that the
      analytical solutions obtained by bi-layer structures provide good estimations for
      tri-layer structures when the epoxy thickness is less than 100 mum. The
      predictions obtained for both systems are shown to provide improved predictions
      by comparing with experimental results reported by Lee et al. [J. Am. Ceram.
      Soc., 2002, 85(8), 2019-2024]. In both systems, the modeling of join/substrate
      creep is shown to be important for the accurate prediction of loading rate
      effects on radial cracking.

PMID- 17200816
TI  - Contact damage in an yttria stabilized zirconia: implications.
AB  - This paper presents the results of a combined experimental and computational
      study of contact damage in a 3 mole% yttria partially stabilized zirconia (3-YSZ)
      that is relevant to hip implants and dental restorations. Contact-induced loading
      in real applications is idealized using Hertzian contact model to explain
      plasticity phenomena and failure mechanisms observed under monotonic and cyclic
      loading. Under monotonic loading, the elastic moduli increase with increasing
      loading levels. Under cyclic loading, the ceramic specimens fail with progressive
      cone cracking. X-ray analyses reveal that stress-induced phase transformation
      (from tetragonal to monoclinic phases) occurs under cyclic contact loading above
      the critical load levels (approximately 8.5 kN). Furthermore, when the cyclic
      loading level (5.0 kN) is less than a critical load levels (7.5 kN) that is
      required to induce surface cone cracks, significant plastic damage is observed in
      the subsurface zone underneath the contact area. These suggest that the cyclic
      contact loading induce both plastic damage and tetragonalto-monoclinic phase
      transformation in the 3-YSZ, leading to significant degradation in long-term
      strength. The implications of the results are discussed for the design of
      zirconia femoral heads in total hip replacements and zirconia crowns in dental
      restoration.

PMID- 17200817
TI  - Lattice energy and mechanical stiffness of hydroxyapatite.
AB  - The lattice energy of the stoichiometric hydroxyapatite is calculated using three
      methods: the thermochemical method called Born-Fajans-Haber cycle (BHFC), the
      semi-empirical electrostatic method based on the generalized Kapustinskii
      equation, and the Glasser-Jenkins unit cell volume method. The three values of
      the lattice energy of the hydroxyapatite derived by the three methods are within
      4% difference to each other (BHFC: 34,191 KJ/mole, generalized Kapustinskii
      equation: 32,808.9 KJ/mole, unit cell volume: 32,997.4 KJ/mole). The Voigt and
      Reuss effective elastic moduli of 19 simple ionic crystals, including those of
      the hydroxyapaptite, are calculated and are found to be linearly dependent on
      their volumetric lattice energy density (LED).

PMID- 17200818
TI  - Cell/surface interactions and adhesion on bioactive glass 45S5.
AB  - This paper examines the effects of surface texture (smooth versus rough) on
      cell/surface interactions on the bioactive glass, 45S5. The cell surface
      interactions associated with cell spreading are studied using cell culture
      experiments. Subsequent energy dispersive x-ray spectroscopy is also used to
      reveal the distributions of calcium, phosphorous, sodium and oxygen on the
      surfaces of the bioactive glasses. The implications of the results are then
      discussed for the applications of textured bioactive glasses in medicine.

PMID- 17200819
TI  - On the measurement of human osteosarcoma cell elastic modulus using shear assay
      experiments.
AB  - This paper presents a method for determining the elastic modulus of human
      osteosarcoma (HOS) cells. The method involves a combination of shear assay
      experiments and finite element analysis. Following in-situ observations of cell
      deformation during shear assay experiments, a digital image correlation (DIC)
      technique was used to determine the local displacement and strain fields. Finite
      element analysis was then used to determine the Young's moduli of HOS cells. This
      involved a match of the maximum shear stresses estimated from the experimental
      shear assay measurements and those calculated from finite element simulations.

PMID- 17200820
TI  - Annealing study of palladium-silver dental alloys: Vickers hardness measurements
      and SEM microstructural observations.
AB  - Three Pd-Ag dental alloys for metal-ceramic restorations, W-1 (Ivoclar Vivadent),
      Rx 91 (Pentron) and Super Star (Heraeus Kulzer), were subjected to isothermal
      annealing for 0.5 hr periods in a nitrogen atmosphere at temperatures from
      approximately 400 degrees to 950 degrees C. The annealing behavior was
      investigated by Vickers hardness measurements (1 kg load) and SEM microstructural
      observations. The highest Vickers hardness occurred at approximately 700 degrees
      C for W-1 and 650 degrees C for Rx 91. For Super Star, there were two peaks in
      hardness at approximately 500 degrees and 650 degrees C. Additional use of light
      indenting loads (25 g for W-1; 10 g for Rx 91 and Super Star) revealed that
      hardness variations during annealing for W-1 and Rx 91 were related to the
      palladium solid solution matrix phase. For Super Star, the lower-temperature peak
      was controlled by multi-phase regions and the higher-temperature peak by the
      matrix phase. While microstructural changes due to annealing were evident with
      the SEM for Rx 91 and Super Star, no correlation was possible for W-1 because of
      its finer-scale microstructure. Although commercial Pd-Ag alloys have a
      relatively narrow composition range, their microstructures and annealing behavior
      can vary because of differences in proportions of secondary elements utilized for
      porcelain adherence and grain refinement elements, as well as other proprietary
      strategies employed by the manufacturers.

PMID- 17200821
TI  - Fatigue limits and SEM/TEM observations of fracture characteristics for three Pd
      Ag dental casting alloys.
AB  - The fatigue limits and fracture characteristics for three Pd-Ag dental casting
      alloys (Super Star, Heraeus Kulzer; Rx 91, Pentron; W-1, Ivoclar Vivadent) were
      studied. Specimens meeting the dimensions for ADA Specifications No. 5 and 38,
      and having the as-cast surface condition, were subjected to heat treatment
      simulating dental porcelain firing cycles and fatigued in air at room temperature
      under uniaxial tension-compression at 10 Hz. A ratio of compressive stress
      amplitude to tensile stress amplitude (R-ratio) of -1 was used. Alloy
      microstructures and fracture surfaces were examined with a scanning electron
      microscope and a transmission electron microscope. Fatigue limits for the three
      alloys had low values of approximately 15% of the yield strength for 0.2%
      permanent tensile strain. Complex fracture surfaces with characteristic
      striations were observed for all three fatigued alloys. Planar slip of
      dislocations occurred in the Pd solid solution matrix, along with dislocation
      precipitate interactions and dislocation networks in the interfaces between the
      precipitates and surrounding matrix. Twinning occurred in the Pd solid solution
      matrix of Rx 91, and within discontinuous precipitates in Super Star and Rx 91.
      The low fatigue limits for these alloys are attributed to their complex
      microstructures and perhaps to casting defects.

PMID- 17200822
TI  - Ion leaching of a glass-ionomer glass: an empirical model and effects on setting
      characteristics and strength.
AB  - The release of ions from a glass-ionomer glass, which in the polyacid matrix
      effects the cross-linking and setting of a cement, can be modelled and initiated
      by acid-treatment in a dilute acid. This study examined the effect of time of
      acetic acid leaching on the working time, setting time, and strength of a model
      GIC. A reactive fluoride glass was immersed in hot acetic acid for 0 (control),
      5, 15, 35, 65, 95 and 125 min, filtered and dried. The glass was mixed with an
      experimental GI liquid in a capsule system and the mixed pastes assessed for
      working and initial setting time. Compressive strength testing was undertaken
      according to ISO9917:2003. Immersion time had a significant effect on both
      working and setting time of the resultant pastes only up to 65 min of immersion,
      and corresponded with a thin-film ion diffusion model. Compressive strength did
      not vary significantly with immersion time. The glass-ionomer setting reaction
      can be conveniently retarded by immersion of the powder in acetic acid, without
      affecting strength. A reactivity model was developed, whereby the effects of
      various changes to the leaching process may be usefully examined.

PMID- 17200823
TI  - HPLC analysis of components released from dental composites with different resin
      compositions using different extraction media.
AB  - Components released from dental composite resins are essential factors in the
      assessment of biocompatibility of these materials. The effect of different
      extraction media on monomer release from composite resins based on different
      monomer types was evaluated. Three types of visible light cured composite resins
      were formulated based on the following monomers: triethylene glycol
      dimethacrylate (TEGDMA), bisphenol A glycerolate dimethacrylate (BisGMA), and
      urethane dimethacrylate (UDMA). Seventy-five composite resin discs were
      fabricated and light cured for 1 min in the absence of oxygen. Extraction media
      used were: distilled water, saline solution, artificial saliva, serum-free
      culture medium, and culture medium with 10% fetal calf serum. The analysis of
      extracts from the composite resins was carried out by High Performance Liquid
      Chromatography (HPLC). Quantifiable amounts of TEGDMA were released into the
      aqueous media. However, BisGMA and UDMA were not detectable in any of the
      extracts from the composite resins. Statistical analysis by one-way ANOVA
      followed by Tukey's test showed that there was a significant difference in TEGDMA
      release between culture media and other media (p < 0.05). From the results of
      this experiment it can be concluded that TEGDMA-based composite resins can
      release a high quantity of monomer into aqueous environments. The type of
      extraction medium may have a significant effect on monomer release from composite
      resins.

PMID- 17200824
TI  - In vitro microhardness of glass ionomer cements.
AB  - This study evaluated the surface microhardness of four glass ionomer cements and
      a composite resin (Fuji IX, Ketac Molar, Vidrion R, Vitromolar and Z 250). Ten
      specimens of each glass ionomer cement with 8.0 mm diameter and 5.0 mm high
      dimensions were made and Vicker's microhardness measurements were taken at 1 day
      and 1 week after initial setting reaction. The results were analyzed using
      Student's T test and Tukey test (p < 0.05) and demonstrated that the values of
      microhardness increased after 1 week, with the exception of Fuji IX. Resin
      composite Z250 presented the greatest values for microhardness.

PMID- 17200825
TI  - Comparative study of the wear behavior of composites for posterior restorations.
AB  - This investigation sought to compare the abrasive wear rates of resin composites
      designed for posterior applications. Seventy-five specimens were fabricated with
      conventional hybrid (Charisma and Filtek Z250) or packable composites (Filtek
      P60, Solitaire II and Tetric Ceram HB), according to a randomized complete block
      design (n = 15). Specimens were finished and polished metallographically and
      subjected to abrasive wear which was performed under a normal load of 13N at a
      frequency of 2 Hz using a pneumatic device (MSM/Elquip) in the presence of a
      mucin-containing artificial saliva. Wear was quantified profilometrically in five
      different locations of each specimen after 1,000, 5,000, 10,000, 50,000 and after
      every each 50,000 through 250,000 cycles. A split-plot ANOVA showed a significant
      difference between the wear resistance of composites (alpha = 0.05). Tukey's test
      ascertained that while the composites Filtek Z250 and Charisma wore significantly
      less than any other of the materials tested, Tetric Ceram HB experienced the
      greatest wear rates. Filtek P60 and Solitaire II showed intermediate rates of
      material removal. The wear pattern of composites proved to be biphasic with the
      primary phase having the faster wear rate. In conclusion, packable resin
      composites may not have superior wear compared to conventional hybrid composites.

PMID- 17200826
TI  - Effect of commercial mouthwashes on the corrosion resistance of Ti-10Mo
      experimental alloy.
AB  - The purpose of this work was to evaluate the effect of three commercial
      mouthwashes on the corrosion resistance of Ti-10Mo experimental alloy.
      Experiments were made at 37.0 +/- 0.5 degrees C in a conventional three
      compartment double wall glass cell containing commercial mouthwashes. Three
      mouthwashes with different active ingredients were tested: (I) 0.05% sodium
      fluoride + 0.03% triclosan; (II) 0.5 g/l cetylpyridinium chloride + 0.05% sodium
      fluoride; (III) 0.12% chlorohexidine digluconate. The assessment of the
      individual effect of active ingredients was studied by using 0.05% sodium
      fluoride. Commercially pure titanium (CP Ti) was used as control. Microstructures
      from Ti-10Mo experimental alloy and CP Ti were also evaluated using optical
      microscopy. Ti-10Mo as-cast alloy shows the typical rapidly cooled dendrites
      microstructure (beta phase) while CP Ti has exhibited a metastable martensitic
      microstructure. Electrochemical behavior of dental materials here studied was
      more affected by mouthwash type than by Ti alloy composition or microstructure.
      In both alloys passivation phenomenon was observed. This process may be mainly
      related to Ti oxides or other Ti species present in spontaneously formed film.
      Small differences in passive current densities values may be connected with
      changes in film porosity and thickness. Protective characteristics of this
      passive film are lower in 0.05% sodium fluoride + 0.03% triclosan mouthwash than
      in the other two mouthwashes tested.

PMID- 17200827
TI  - Evaluation of surface characteristics of dental composites using profilometry,
      scanning electron, atomic force microscopy and gloss-meter.
AB  - The aim of this in vitro investigation was to compare various roughness and
      topography measurement methods to characterize the surface quality in several
      types of resin composites. The initial surface quality of several resin
      composites was compared. The materials evaluated were of three categories: i)
      hybrid: TPH Spectrum; ii) reinforced microfill: Micronew and iii) microhybrid:
      Synergy Duo, Esthet-X, Point.4 and Palfique Estelite. Three Groups of identical
      disk-shaped specimens (10 x 1.5 mm) were prepared from each material (n = 6) and
      polished with Soflex discs. Macro-roughness (Ra) was measured with Group 1 by 2-D
      profilometry. Atomic Force Microscopy (AFM) gave 3-D images and micro-roughness
      (Ra) of Group 2. Surface optical gloss at 60 degrees was determined for Group 3.
      Specimens of each material were also studied by scanning electron microscopy.
      Macro-Ra values (microm) ranged from 0.30 to 0.56. Micro-Ra values ranged from
      0.03 to 0.14 and they differed from macro-Ra values in ranking order. Percentage
      Gloss values ranged from 30.6 to 70.1%. The results revealed that micro-roughness
      showed a high correlation with gloss values (r = 0.93), whilst macro-roughness
      did not (r = 0.62). Moreover, the AFM method showed higher capability to
      distinguish surface roughness compared with the 2-D profilometry and to reveal
      more detailed definition of surface texture than the examination under SEM.

PMID- 17200828
TI  - Combined effect of staining substances on the discoloration of esthetic Class V
      dental restorative materials.
AB  - The purpose of this study was to determine the combined effect of an organic
      substance (mucin as a substitute for salivary organic substances), chlorhexidine,
      and an iron compound/tea solution on the changes in the color of esthetic Class V
      dental restorative materials. Color of a glass ionomer, resin-modified glass
      ionomer, compomer and flowable resin composite of A2 shade, respectively, was
      determined according to the CIELAB color scale relative to the standard
      illuminant D65. Color was measured at baseline, and after sequential immersion in
      the following substances: Step-1, mucin in PBS (MCP) for 48 h; Step-2,
      chlorhexidine (CHX) for 24 h; Step-3, iron compound (IRN) or tea solution (TEA)
      up to 7 days; and Step-4, ultrasonic cleaning for 1 h. Color change (DeltaE(ab
      )*) was calculated by the equation: DeltaE(ab)* = [(DeltaL*)(2) + (Deltaa*)(2) +
      (Deltab*)(2)](1/2), of which DeltaL(*) indicates changes in value, Deltaa(*)
      indicates changes in red-green parameter and Deltab(*) indicates changes in
      yellow-blue parameter. DeltaE(ab)* values after immersion in MCP and CHX were
      compared, and DeltaE(ab)* values after immersion in IRN or TEA, and subsequent
      ultrasonic cleaning were compared with respect to the restorative material and
      immersion substance. DeltaE(ab)* and changes in the color parameters (DeltaL(*),
      DeltaC(ab)* and DeltaH(ab)*) were analyzed by repeated measures, analysis of
      variance and a post-hoc test at the 0.05 level of significance. Color changes
      after immersion in MCP were acceptable (DeltaE(ab)* < 3.3), and those after
      immersion in CHX were generally acceptable. The range of DeltaE(ab)* values after
      immersion in IRN was 3.1-19.6, and that after ultrasonic cleaning was 2.4-9.6.
      The range of DeltaE(ab)* values after immersion in TEA was 10.7-21.1, and that
      after ultrasonic cleaning was 11.9-14.5. Color changes of four Class V
      restorative materials after combined treatment with mucin, chlorhexidine and an
      iron compound/tea solution were not acceptable. Colors did not recover to their
      original values after ultrasonic cleaning. Modifications on the surface of a
      restoration should be considered to reduce stain accumulation.

PMID- 17200829
TI  - Age-hardening behavior of a low-gold dental alloy.
AB  - The age-hardening behaviors of a low gold dental alloy were studied by means of
      differential scanning calorimetry, hardness testing, X-ray diffraction, optical
      microscopy and transmission election microscopy. Two distinct hardening behaviors
      were found at two different aging temperatures. Age-hardening at 290 degrees C
      was attributed to the formation of the metastable AuCuI' ordered phase, and the
      gradual softening in the overaging stage resulted from the slow growth of this
      phase. The rapid increase in hardness in the early stage at 495 degrees C was due
      to the precipitation of the metastable AuCuI' or/and AuCuII' ordered phases, and
      the rapid decrease in hardness in the overaging stage was a consequence of the
      growth of these phases and the loss of the coherency strain at the interface
      between the spindal-like AuCuI platelets and the matrix.

PMID- 17200830
TI  - Intraoral osteotomies using piezosurgery for distraction in an infant with Pierre
      Robin sequence.
AB  - Airway management in infants with Pierre Robin sequence (PRS) is often
      challenging. Advancement of the tongue base using mandibular distraction in
      neonates can avoid tracheotomy and is increasingly propagated. The osteotomies
      can be performed via intra- and extraoral approaches. Nowadays, for precise bone
      cutting, piezosurgical devices have been introduced in maxillofacial surgery,
      which we used for osteotomies via the intraoral approach in the 7-week-old
      patient presented in this study. Instead of a preoperative CT scan, a 3D data set
      was generated preoperatively in the operating theatre using a 3D C-arm system.
      After bilateral transcutaneous pin placement and osteotomies, a second 3D data
      set was acquired. Primary and secondary reconstructions clearly visualized the
      patient's bone despite the low level of ossification in newborns and the presence
      of a large amount of metal implants. In view of the low level of radiation
      exposure going along with the 3D C-arm imaging, a follow-up examination after
      removal of the distractors was performed. With this report of a 7-week-old female
      infant with the diagnosis of PRS, we want to extend the surgical and diagnostic
      armamentarium for the treatment of infants with PRS.

PMID- 17200832
TI  - Evaluation of the prescription and utilization patterns of statins in an Italian
      local health unit during the period 1994-2003.
AB  - OBJECTIVES: The prescription pattern of statins in the Local Health Unit (LHU) of
      Treviso (northern Italy) over a 10-year period was evaluated, with the aim of
      evaluating the persistence with and adherence to therapy. METHODS: Data on 21,393
      subjects who received at least one prescription for statins during the period
      between January 1, 1994 and December 31, 2003 were retrieved from the LHU
      database in order to track the pharmacological history of individual patients.
      The data included age, sex, drug formulation, strength, number of drug packages
      prescribed, and prescription date. The adopted indicators for drug utilization
      included the Defined Daily Dose (DDD), the Received Daily Dose (RDD), and a
      surrogated Prescribed Daily Dose (sPDD), extrapolated from available prescription
      data. An Adherence to Therapy Index (ATI) was calculated from the ratio between
      the amount of drug actually prescribed and the amount of sPDD. Based on the ATI,
      patients were grouped into non-adherent, poor-adherent, and good-adherent groups.
      The distribution of adherence level among patient-age classes and statin
      prescribed patients in primary or secondary prevention was evaluated. RESULTS:
      All drug-utilization indicators showed an increase in statin use over the study
      period in terms of both the number of prescribed patients and the sPDD.
      Persistence with and adherence to therapy remained low, with a 50%
      discontinuation rate in the first year, and persistent patients did not follow
      the therapy regularly. Patients in secondary prevention were the most adherent to
      their drug regimen, although only 41% of these had a good compliance.
      CONCLUSIONS: Our findings suggest an increase in statin use which is, however,
      accompanied by poor patient persistence with and adherence to statin therapy.

PMID- 17200831
TI  - Inhibitory potential of nonsteroidal anti-inflammatory drugs on UDP
      glucuronosyltransferase 2B7 in human liver microsomes.
AB  - OBJECTIVE: A number of nonsteroidal anti-inflammatory drugs (NSAIDs) are subject
      to glucuronidation in humans, and UDP-glucuronosyltransferase (UGT) 2B7 is
      involved in the glucuronidation of many NSAIDs. The objective of this study was
      to identify a NSAID with potent inhibitory potential against UGT2B7 using liquid
      chromatography with tandem mass spectrometry (LC-MS/MS). METHODS: A rapid
      screening method for detecting the inhibitory potential of various drugs against
      UGT2B7 was established using a LC-MS/MS system. The effects of nine NSAIDs
      (acetaminophen, diclofenac, diflunisal, indomethacin, ketoprofen, mefenamic acid,
      naproxen, niflumic acid, and salicylic acid) against UGT2B7-catalyzed 3'-azido-3'
      deoxythymidine glucuronidation (AZTG) were investigated in human liver microsomes
      (HLM) and recombinant human UGT2B7. RESULTS: Mefenamic acid inhibited AZTG most
      potently, with an IC(50) value of 0.3 microM, and its inhibition type was not
      competitive. The IC(50) values for diclofenac, diflunisal, indomethacin,
      ketoprofen, naproxen, and niflumic acid against AZTG were 6.8, 178, 51, 40, 23,
      and 83 microM, respectively, while those for acetaminophen and salicylic acid
      were >100 microM. The IC(50) values for NSAIDs against AZTG in recombinant human
      UGT2B7 were similar to those obtained in HLM. CONCLUSION: The method established
      in this study is useful for identifying drugs with inhibitory potential against
      human UGT2B7. Among the nine NSAIDs investigated, mefenamic acid had the
      strongest inhibitory effect on UGT2B7-catalyzed AZTG in HLM. Thus, caution might
      be exercised when mefenamic acid is coadministered with drugs possessing UGT2B7
      as a main elimination pathway.

PMID- 17200833
TI  - The effect of simvastatin, ezetimibe and their combination on the lipid profile,
      arterial stiffness and inflammatory markers.
AB  - OBJECTIVE: Arterial stiffness and highly sensitive C-reactive protein (hsCRP)
      serum level predict the risk for cardiovascular events. The most commonly used
      drugs for lowering cholesterol levels, the statins, also have anti-inflammatory
      effects and can decrease arterial stiffness. Ezetimibe is the first drug of a new
      class of cholesterol absorption inhibitors in common use and, to date, its effect
      on arterial stiffness has not yet been studied. The aim of this study was to
      compare the effect of simvastatin and ezetimibe, both singly and in combination,
      on arterial stiffness and hsCRP serum concentration in hypercholesterolemic
      patients. METHODS: Forty hypercholesterolemic patients were studied. Group1
      comprised previously untreated patients, who received simvastatin at doses of 40
      mg/day during the study; group 2 comprised patients previously treated with
      simvastatin at 40 mg/day, who received simvastatin at 80 mg/day during the study;
      group 3 consisted of patients previously untreated, who received ezetimibe at
      doses of 10 mg/day during the study; group 4 comprised patients previously
      treated with simvastatin at 40 mg/day, who received simvastatin at 40 mg/day and
      ezetimibe at 10 mg/day during the study. Arterial stiffness expressed as the
      Augmentation Index (AIx) (assessed by pulse wave analysis), the lipid profile and
      the hsCRP level were measured at baseline and after 3 months of treatment.
      RESULTS: The reduction in low-density lipoprotein (LDL) after treatment was
      significantly greater in groups 1 and 4 (39.9 and 35.7%) than in groups 2 and 3
      (17.7 and 16.9%; p = 0.005). The AIx decreased significantly only in group 1
      patients, from 30.2 +/- 8.3% before treatment to 21.6 +/- 6.5% after treatment (p
      < 0.001). Changes in hsCRP paralleled the changes in AIx, with a significant
      decrease in patients in group 1 only, from 2.8 +/- 2.5 mg/L before treatment to
      1.6 +/- 1.5 mg/L after treatment (p = 0.016). CONCLUSION: Ezetimibe as a
      monotherapy had no effect on arterial stiffness or hsCRP, while the
      administration of simvastatin at 40 mg per day improved arterial stiffness and
      CRP. However, increasing the dose of simvastatin or administering ezetimibe in
      combination with simvastatin had no beneficial effects on arterial stiffness.

PMID- 17200834
TI  - Influence of initial use of serotonergic antidepressants on antiparkinsonian drug
      use in levodopa-using patients.
AB  - OBJECTIVE: To assess whether there is an association between initial use of
      serotonergic antidepressants and changes in antiparkinsonian drug treatment.
      METHODS: A retrospective cohort study was performed with the PHARMO record
      linkage system. All patients from 1994 until 2004 of 40 years or older who were
      first time users of an antidepressant and who had used a levodopa-containing drug
      at least 180 days before initiation of the antidepressant were included. The
      maximum follow-up time was 180 days. The first change in antiparkinsonian drug
      treatment, defined as an increase in the daily dosage of any antiparkinsonian
      drug, the start of a new antiparkinsonian drug or a change in the dosage form
      during the follow-up period, was taken as an endpoint. Antidepressants were
      classified in two ways: according to their class [selective serotonin reuptake
      inhibitors (SSRI), tricyclic antidepressants (TCA) or other antidepressants] or
      by the extent of their inhibition of serotonin reuptake (high, intermediate or
      low). RESULTS: A total of 221 patients was included in our study. The adjusted
      hazard ratio for a change in antiparkinsonian drug treatment was 0.7 (95% CI 0.3
      1.5) comparing SSRI with TCA users, and it was 0.9 (95% CI 0.4-2.1) comparing
      users of other antidepressants with TCA users. The adjusted hazard ratio for a
      change in antiparkinsonian drug treatment was 0.6 (95% CI 0.3-1.4) comparing
      users of antidepressants with high versus low extent of inhibition of serotonin
      reuptake, and it was 0.7 (95% CI 0.3-1.4) comparing users of antidepressants with
      intermediate versus low extent of inhibition of serotonin reuptake. CONCLUSION:
      Based on these observations, we found no evidence to be more cautious using SSRIs
      or serotonergic antidepressants compared to other antidepressants in patients
      with Parkinson's disease.

PMID- 17200835
TI  - Medication administered to children from 0 to 7.5 years in the Avon Longitudinal
      Study of Parents and Children (ALSPAC).
AB  - OBJECTIVE: To present data on the parentally-reported use of all types of
      medicinal products in children from 0 to 7.5 years, in a large cohort in south
      west England. METHODS: Participants in the population-based Avon Longitudinal
      Study of Parents and Children (ALSPAC) have been sent self-completion postal
      questionnaires since they were enrolled during pregnancy. The use of medicinal
      products has been obtained from questionnaires sent out when the study children
      were 4 weeks, 54, 78 and 91 months old. RESULTS: The data included prescription,
      over-the-counter and complementary and alternative medicines. Around three
      quarters of study children were exposed to some form of medicinal product before
      8 weeks of age. Dermatological preparations were the most commonly used products
      in young babies. Activated dimeticone, for treatment of colic and flatulence, was
      given to 16% of babies and gripe water was used by 13%. Other commonly reported
      products included oral and topical antifungals and ophthalmic antibiotics.
      Several OTC products, not licensed for use in this age group, were reported. At
      each of the older ages surveyed, over 95% of children had used some form of
      medicinal product within the previous 12-18 months. Use of several product
      categories was higher at 54 months than at 78 or 91 months, such as topical
      steroids, analgesics (mostly paracetamol) and systemic antibiotics (mainly
      amoxicillin). Conversely, use of other categories, such as asthma medication,
      throat preparations (sprays and lozenges) and anti-inflammatory products,
      increased with increasing age. CONCLUSION: Parentally-reported use of medicinal
      products in the ALSPAC study children appears to be consistent with data from
      other sources. The use of medicinal products by young children is high and does
      not always conform to the product labelling.

PMID- 17200837
TI  - The effect of topiramate on energy balance in obese men: a 6-month double-blind
      randomized placebo-controlled study with a 6-month open-label extension.
AB  - OBJECTIVE: Topiramate (TPM) has been reported to reduce body weight beyond a
      placebo in the treatment of obese participants, but the effect of this agent on
      components of energy balance has not yet been established in humans. Thus, the
      aim of this study was to study the impact of TPM on food preferences, measures of
      satiety, food intake, resting metabolic rate (RMR), and 24-h energy expenditure.
      METHODS: The study design consisted of a 6-month, single-center, randomized,
      double-blind, parallel group, placebo-controlled trial with a 6-month open-label
      extension. The study included 68 sedentary men with abdominal obesity (waist
      circumference > or = 100 cm), of between 25 and 55 years of age, with a
      dyslipidemic profile and a body mass index (BMI) > or = 27 and < or = 40 kg/m(2).
      RESULTS: Treatment with TPM produced significant changes in anthropometric
      variables and body composition compared with placebo. However, at the end of the
      1-year study, the placebo/TPM group showed similar weight loss and reduction in
      body fatness compared with the TPM/TPM group. For instance, at the end of the 12
      month intervention, mean percentage of body weight loss from baseline was about 
      5% in both groups (-4 kg fat loss). Topiramate treatment reduced energy intake,
      be it in the context of an ad libitum buffet-type meal or under free living
      conditions. The 24-h daily energy expenditure (DEE) assessed by whole-body
      indirect calorimetry adjusted for body weight and age was not altered by TPM
      treatment. CONCLUSION: Topiramate treatment produced significantly greater weight
      loss than placebo and the majority of this loss was explained by a decrease in
      body fat stores. Most of the weight loss effect produced by TPM therapy was
      observed within a period of 6 months. Finally, TPM treatment had an impact on
      energy balance through a reduction in food intake that appears to have created an
      energy deficit of about 30,000-40,000 kcal compared with treatment with the
      placebo over 6 months.

PMID- 17200838
TI  - The effect of MK-0524, a prostaglandin D(2) receptor antagonist, on prostaglandin
      D (2)-induced nasal airway obstruction in healthy volunteers.
AB  - INTRODUCTION: Nasal congestion in allergic rhinitis results from tissue edema and
      vasodilatation in the nasal mucosa. Of the mediators released by mast cells in
      response to allergens, prostaglandin (PG) D(2) is regarded as the most potent
      inducer of nasal congestion. Intranasal administration of PGD(2) reproduces the
      nasal blockade experienced by patients with seasonal allergic rhinitis (SAR) via
      its action on the PGD(2) (DP) receptor to induce nasal vasodilatation. Intranasal
      challenge with PGD(2) can be a useful tool for evaluating DP-receptor
      antagonists. OBJECTIVE: The main purpose of this study was to examine the ability
      of MK-0524, a DP receptor antagonist in development for the treatment of SAR, to
      block PGD(2) induced nasal congestion in healthy volunteers. METHODS: To this
      end, a double-blind, placebo-controlled, randomized, 3-period study was performed
      in 15 healthy subjects. During each period, subjects received MK-0524 25 mg, MK
      0524 100 mg or placebo qd for 3 days. Twenty-four hours following the last dose,
      nasal provocations with PGD(2) were performed to determine the PD(75), which is
      the intranasal dose of PGD(2) that provokes a 75% increase in baseline total
      nasal airway resistance as performed by active anterior rhinomanometry. RESULTS:
      Following treatment with MK-0524, the PD(75) (mean+/-SD) was significantly
      shifted from 15.8 +/- 18.3 mug/nostril during the placebo period to more than 512
      mug/nostril both following the 25- and 100-mg (maximum challenge dose tested)
      dose regimen. CONCLUSION: Whether this >45 fold increase in PD(75) will induce a
      clinically meaningful effect of MK-0524 will require clinical study in
      participants with SAR.

PMID- 17200836
TI  - Inhibition of CYP3A4 and CYP3A5 catalyzed metabolism of alprazolam and quinine by
      ketoconazole as racemate and four different enantiomers.
AB  - OBJECTIVE: The antifungal drug ketoconazole (KTZ) is known as an inhibitor of,
      especially, the CYP3A subfamily, which catalyzes the metabolism of a large
      variety of drugs. Interactions between KTZ and CYP3A substrates have been
      reported both in vivo and in vitro. Most of them, however, involved the KTZ
      racemate. KTZ racemate and the separate enantiomers, 2R,4R; 2R,4S; 2S,4S, and
      2S,4R, were evaluated for their selectivity in inhibiting alprazolam and quinine
      metabolism. METHODS: The inhibition of alprazolam and quinine metabolism was
      studied in an in vitro system of human liver microsomes (HLM), recombinant of
      CYP3A4 and CYP3A5. The concentrations of formed 3-hydroxyquinine and 4- and alpha
      hydroxyalprazolam were measured by HPLC and LC-MS, respectively. RESULTS: Quinine
      3-hydroxylation was catalyzed to a similar extent by CYP3A4 and CYP3A5. The
      formation rate of 4-hydroxyalprazolam was higher than that of alpha
      hydroxyalprazolam for each HLM, CYP3A4 and CYP3A5. KTZ racemate and enantiomers
      showed differential inhibitory effects of quinine and alprazolam metabolism.
      Quinine metabolism catalyzed by HLM, CYP3A4 and CYP3A5 was potently inhibited by
      the trans-enantiomer KTZ 2S,4S, with IC(50) value of 0.16 microM for HLM, 0.04
      microM for CYP3A4 and 0.11 microM for CYP3A5. The same enantiomer showed the
      lowest IC(50) values of 0.11 microM for HLM and 0.04 microM for CYP3A5 with
      respect to alprazoalm 4-hydroxylation and also the same pattern for
      alprazolamalpha-hydroxylation, 0.13 microM for HLM and 0.05 microM for CYP3A5.
      Alprazolam metabolism (both alpha- and 4- hydroxylations) catalyzed by CYP3A4 was
      inhibited potently by the cis-enantiomer KTZ 2S,4R, with IC(50) values of 0.03
      microM. CONCLUSIONS: Alprazolam and quinine metabolism is catalyzed by both
      CYP3A4 and CYP3A5. The present study showed that different KTZ enantiomers
      inhibit CYP3A4 and CYP3A5 to different degrees, indicating that structural
      differences among the enantiomers would be related to their inhibitory potency on
      these two enzymes.

PMID- 17200839
TI  - LigProf: a simple tool for in silico prediction of ligand-binding sites.
AB  - With the increasing amount of data provided by both high-throughput sequencing
      and structural genomics studies, there is a growing need for tools to augment
      functional predictions for protein sequences. Broad descriptions of function can
      be provided by establishing the presence of protein domains associated with a
      particular function. To extend the domain-based annotation, LigProf provides
      predictions of potential ligands that bind to a protein, as well as critical
      residues that stabilize ligands. A P-value statistic for estimating the
      significance of motif occurrence is provided for all sites. Although the
      usefulness of the method will rise with increasing numbers of
      crystallographically solved molecules deposited in the PDB database, we show that
      it can already be applied successfully to the highly represented ligand-bound
      protein kinase domains of viral and human origin. The LigProf webserver is freely
      available at: http://www.cropnet.pl/ligprof . At present, LigProf descriptors
      annotate and extend major protein families from the PfamA database.

PMID- 17200841
TI  - Emergence of rare sapovirus genotype among infants and children with acute
      gastroenteritis in Japan.
AB  - A total of 1,154 fecal specimens from infants and children with acute
      gastroenteritis in five cities in Japan (Maizuru, Tokyo, Sapporo, Saga, and
      Osaka), collected from July 2003 to June 2005, were tested for the presence of
      diarrheal viruses by reverse transcriptase multiplex PCR. Overall, 469 of 1,154
      (40.6%) were positive for diarrheal viruses, of which 49 (10.4%) were positive
      for sapovirus. The peak of sapovirus infection shifted from April-June in 2003
      2004 to October-December in 2004-2005. The observations show that maximum
      sapovirus prevalence can occur during warmer seasons. Sapovirus was subjected to
      molecular genetic analysis by sequencing. The results indicated that sapovirus
      genogroup I was a dominant group (100%). Sapovirus strains detected in this study
      were further classified into four genotypes (GI/1, GI/4, GI/6, and GI/8). Of
      these, sapovirus GI/1 was the most predominant, followed by sapovirus GI/6; these
      accounted for 93% (13 of 14) and 7% (1 of 14), respectively, in 2003-2004.
      However, it was noteworthy that sapovirus GI/6 suddenly emerged to become the
      leading genotype, accounting for 77% (27 of 35) of isolates in 2004-2005. This is
      believed to be the first report of the changing distribution of sapovirus
      genotypes and of the emergence of the rare sapovirus GI/6.

PMID- 17200842
TI  - First isolation of vancomycin-resistant enteroccoci and spread of a single clone
      in a university hospital in northwestern Turkey.
AB  - Reported here is the first isolation of vancomycin-resistant Enterococcus (VRE)
      at a hospital in northwestern Turkey and a description of the ensuing outbreak
      investigation. The first isolate was obtained from a wound culture of a patient
      in an intensive care unit. Thereafter, a total of 205 rectal swabs, 67 skin swabs
      and 123 environmental samples were screened, revealing five more VRE isolates.
      All isolates showed similar antibiotic resistance patterns, except for two that
      differed regarding gentamicin resistance. The vanA gene was present in all
      isolates. Pulsed-field gel electrophoresis demonstrated that all isolates
      belonged to a single clone, with the gentamicin-resistant isolates demonstrating
      two-band differences. This is the first outbreak to be caused by spread of a
      single VRE clone in Turkey; it was successfully controlled by strict adherence to
      appropriate infection control practices.

PMID- 17200840
TI  - Stenotrophomonas maltophilia pneumonia in cancer patients without traditional
      risk factors for infection, 1997-2004.
AB  - In order to elucidate the spectrum of Stenotrophomonas maltophilia pneumonia in
      cancer patients without traditional risk factors, 44 cancer patients (cases) with
      S. maltophilia pneumonia in whom S. maltophilia pneumonia risk factors were not
      present were compared with two S. maltophilia pneumonia risk groups (controls)
      including 43 neutropenic non-intensive care unit (ICU) and 21 non-neutropenic ICU
      patients. The case and control patients had similar demographic and underlying
      clinical characteristics. Compared with case patients with S. maltophilia
      pneumonia, neutropenic patients had higher exposure to carbapenem antibiotics (58
      vs. 41%; p < 0.03), more frequent hematologic malignancy (95 vs. 64%; p <
      0.0003), and they presented with concurrent bacteremia more often (23 vs. 0%; p <
      0.0005). Patients with S. maltophilia pneumonia in the ICU needed vasopressor
      therapy more frequently than cases (62 vs. 5%; p < 0.0001). Hospital-acquired S.
      maltophilia pneumonia was more common among controls than cases (98 vs. 61%; p <
      0.000002). Among the cases, 15 (34%) received outpatient oral antimicrobial
      therapy, while 29 were hospitalized and eight (28%) were subsequently admitted to
      the ICU. The mean duration of ICU stay, even among these eight patients (19 +/-
      40 days), was comparable to that of patients with neutropenia (23 +/- 26 days)
      and those who developed S. maltophilia pneumonia during their ICU stay (34 +/- 22
      days; p = 0.46). The overall infection-associated mortality in the 108 patients
      with S. maltophilia pneumonia was 25%. Twenty percent of patients without
      traditional risk factors for S. maltophilia pneumonia died due to progressive
      infection. In a multivariate logistic regression analysis, only admission to the
      ICU predicted death (odds ratio 33; 95% confidence interval, 4.51-241.2; p <
      0.0006). The results of this study indicate S. maltophilia pneumonia is a serious
      infection even in non-neutropenic, non-ICU patients with cancer.

PMID- 17200843
TI  - Contrast-enhanced magnetic resonance angiography of persistent fifth aortic arch
      in children.
AB  - BACKGROUND: Cine angiography and echocardiography have been utilized to diagnose
      congenital aortic arch anomalies. However, the visualization of great vessels by
      echocardiography is limited, while cine angiography requires cardiac
      catheterization with ionizing radiation. Contrast-enhanced magnetic resonance
      angiography (MRA) is a noninvasive modality suitable for visualization of
      congenital aortic arch anomalies. OBJECTIVE: To evaluate the utility of contrast
      enhanced MRA in the diagnosis of persistent fifth aortic arch, a rare congenital
      aortic arch anomaly, and to compare the diagnostic accuracy of MRA with that of
      echocardiography and cine angiography. MATERIALS AND METHODS: In four pediatric
      patients, contrast-enhanced MRA studies were performed for diagnosing persistent
      fifth aortic arch. The findings of MRA were compared with echocardiographic
      findings and confirmed by cine angiography and operation. RESULTS: Transthoracic
      surface echocardiography noted an aberrant vessel arising from the ascending
      aorta in two of four patients; the etiology of this vessel was uncertain. In the
      other two patients a diagnosis of coarctation was made. Of the four patients,
      only one was diagnosed with interruption of the aortic arch. Contrast-enhanced
      MRA clarified uncertain echocardiographic findings, enabling the correct
      diagnosis of persistent fifth aortic arch with fourth aortic arch interruption in
      all four patients. CONCLUSION: Contrast-enhanced MRA is a safe, accurate, and
      fast imaging technique for the evaluation of persistent fifth aortic arch and may
      obviate the need for conventional cine angiography. Cardiac catheterization may
      be reserved for some types of complicated congenital heart disease and for
      obtaining hemodynamic information.

PMID- 17200844
TI  - Radiography after unexpected death in infants and children compared to autopsy.
AB  - BACKGROUND: Postmortem radiography may reveal skeletal and soft-tissue
      abnormalities of importance for the diagnosis of cause of death. OBJECTIVE: To
      review the radiographs of children under 3 years of age who had died suddenly and
      unexpectedly. To compare the radiological and autopsy findings evaluating
      possible differences in children dying of SIDS and of an explainable cause.
      MATERIALS AND METHODS: A total of 110 consecutive skeletal surveys performed
      between 1998 and 2002 were reviewed. All but one were performed before autopsy
      and comprised AP views of the appendicular and axial skeleton and thorax/abdomen,
      lateral views of the axial skeleton and thorax, and two oblique views of the
      ribs. Radiography and autopsy findings were compared. RESULTS: Causes of death
      were classified as SIDS/borderline SIDS (n = 52) and non-SIDS (n = 58), with one
      case of abuse. In 102 infants there were 150 pathological findings, 88 involving
      the chest, 24 skeletal, and 38 miscellaneous findings. The radiological
      pathological agreement was poor concerning pulmonary findings. Skeletal findings
      were sometimes important for the final diagnosis. CONCLUSIONS: Radiography
      revealed many skeletal and soft-tissue findings. Pulmonary pathology was most
      frequently found, but showed poor agreement with autopsy findings. Recognizing
      skeletal findings related to abuse is important, as these may escape recognition
      at autopsy.

PMID- 17200845
TI  - Determination of water-soluble and insoluble (dilute-HCl-extractable) fractions
      of Cd, Pb and Cu in Antarctic aerosol by square wave anodic stripping
      voltammetry: distribution and summer seasonal evolution at Terra Nova Bay
      (Victoria Land).
AB  - Eight PM10 aerosol samples were collected in the vicinity of the "Mario
      Zucchelli" Italian Antarctic Station (formerly Terra Nova Bay Station) during the
      2000-2001 austral summer using a high-volume sampler and precleaned cellulose
      filters. The aerosol mass was determined by differential weighing of filters
      carried out in a clean chemistry laboratory under controlled temperature and
      humidity. A two-step sequential extraction procedure was used to separate the
      water-soluble and the insoluble (dilute-HCl-extractable) fractions. Cd, Pb and Cu
      were determined in the two fractions using an ultrasensitive square wave anodic
      stripping voltammetric (SWASV) procedure set up for and applied to aerosol
      samples for the first time. Total extractable metals showed maxima at midsummer
      for Cd and Pb and a less clear trend for Cu. In particular, particulate metal
      concentrations ranged as follows: Cd 0.84-9.2 microg g(-1) (average 4.7 microg g(
      1)), Pb 13.2-81 microg g(-1) (average 33 microg g(-1)), Cu 126-628 microg g(-1)
      (average 378 microg g(-1)). In terms of atmospheric concentration, the values
      were: Cd 0.55-6.3 pg m(-3) (average 3.4 pg m(-3)), Pb 8.7-48 pg m(-3) (average 24
      pg m(-3)), Cu 75-365 pg m(-3) (average 266 pg m(-3)). At the beginning of the
      season the three metals appear widely distributed in the insoluble (HCl
      extractable) fraction (higher proportions for Cd and Pb, 90-100%, and lower for
      Cu, 70-90%) with maxima in the second half of December. The soluble fraction then
      increases, and at the end of the season Cd and Pb are approximately
      equidistributed between the two fractions, while for Cu the soluble fraction
      reaches its maximum level of 36%. Practically negligible contributions are
      estimated for crustal and sea-spray sources. Low but significant volcanic
      contributions are estimated for Cd and Pb (approximately 10% and approximately
      5%, respectively), while there is an evident although not quantified marine
      biogenic source, at least for Cd. The estimated natural contributions (possibly
      including the marine biogenic source) cannot account for the high fractions of
      the metal contents, particularly for Pb and Cu, and this suggests that pollution
      from long-range transport is the dominant source.

PMID- 17200846
TI  - Multivariate optimization of a microwave-assisted leaching procedure using dilute
      acid solutions, for FAAS determination of Cu, Fe, Mn, and Zn in
      multivitamin/multimineral supplements.
AB  - This paper reports the development of a microwave-assisted procedure for leaching
      of copper, iron, manganese, and zinc from multivitamin/multimineral supplements
      by use of dilute acid before determination by flame atomic absorption
      spectrometry (FAAS). A Doehlert design was used to find optimum conditions for
      the procedure by use of response-surface methodology. Three variables (acid
      concentration in the leaching solution, irradiation time, and irradiation power)
      were used as factors in the optimization study for two acids, HCl and HNO(3).
      Final working conditions were established as a compromise between the optimum
      values for each analyte, taking into consideration the robustness of the
      procedure. The best leaching results were obtained with HNO(3) and the acid
      concentration, irradiation time, and irradiation power used were 0.70 mol L(-1),
      15 min and 360 W, respectively. The accuracy of the optimized procedure was
      evaluated by comparison with a well-established closed-vessel microwave
      dissolution technique.

PMID- 17200849
TI  - Study of the dynamics of surface molecules by time-resolved sum-frequency
      generation spectroscopy.
AB  - Sum-frequency generation (SFG) is a nonlinear laser-spectroscopy technique
      suitable for analysis of adsorbed molecules. The sub-monolayer sensitivity of SFG
      spectroscopy enables vibrational spectra to be obtained with high specificity for
      a variety of molecules on a range of surfaces, including metals, oxides, and
      semiconductors. The use of ultra-short laser pulses on time-scales of picoseconds
      also makes time-resolved measurements possible; this can reveal ultrafast
      transient changes in molecular arrangements. This article reviews recent time
      resolved SFG spectroscopy studies revealing site-hopping of adsorbed CO on metal
      surfaces and the dynamics of energy relaxation at water/metal interfaces.

PMID- 17200847
TI  - Monitoring of PAHs in air by collection on XAD-2 adsorbent then microwave
      assisted thermal desorption coupled with headspace solid-phase microextraction
      and gas chromatography with mass spectrometric detection.
AB  - Microwave-assisted thermal desorption (MAD) coupled to headspace solid-phase
      microextraction (HS-SPME) has been studied for in-situ, one-step, sample
      preparation for PAHs collected on XAD-2 adsorbent, before gas chromatography with
      mass spectrometric detection. The PAHs on XAD-2 were desorbed into the extraction
      solution, evaporated into the headspace by use of microwave irradiation, and
      absorbed directly on a solid-phase microextraction fiber in the headspace. After
      desorption from the SPME fiber in the hot GC injection port, PAHs were analyzed
      by GC-MS. Conditions affecting extraction efficiency, for example extraction
      solution, addition of salt, stirring speed, SPME fiber coating, sampling
      temperature, microwave power and irradiation time, and desorption conditions were
      investigated. Experimental results indicated that extraction of 275 mg XAD-2,
      containing 10-200 ng PAHs, with 10-mL ethylene glycol-1 mol L(-1) NaCl solution,
      7:3, by irradiation with 120 W for 40 min (the same as the extraction time), and
      collection with a PDMS-DVB fiber at 35 degrees C, resulted in the best extraction
      efficiency. Recovery was more than 80% and RSD was less than 14%. Optimum
      desorption was achieved by heating at 290 degrees C for 5 min. Detection limits
      varied from 0.02 to 1.0 ng for different PAHs. A real sample was obtained by
      using XAD-2 to collect smoke from indoor burning of joss sticks. The amounts of
      PAHs measured varied from 0.795 to 2.53 ng. The method is a simple and rapid
      procedure for determination of PAHs on XAD-2 absorbent, and is free from toxic
      organic solvents.

PMID- 17200850
TI  - Matrix-matched quantitative analysis of trace-elements in calcium carbonate
      shells by laser-ablation ICP-MS: application to the determination of daily scale
      profiles in scallop shell (Pecten maximus).
AB  - A micro-scale method has been developed for analysis of trace-element
      concentration profiles in the calcium carbonate shell of the Great Scallop
      (Pecten maximus). UV laser ablation at 266-nm coupled with ICP-MS detection was
      used to analyse daily calcite striae of shell samples to obtain high temporal
      resolution of trace element incorporation. Analysis of scallop shells was
      carefully examined to determine the quality of calcium carbonate ablation and
      calibration. An accurate external calibration method based on matrix matching was
      developed. Twelve sodium-free enriched calcium carbonate standards containing up
      to twenty-four elements were prepared, by co-precipitation with aqueous ammonia
      and NH(4)HCO(3), and subsequently back-calibrated in the laboratory. These
      CaCO(3) standards were found to be homogenous and their use enabled sensitive
      quantitative analysis (detection limits of a few ng g(-1)) over a wide range of
      concentrations (0.1 to 500 microg g(-1)). Use of these CaCO(3) standards was also
      evaluated by analysis of three calcium-rich certified reference materials.
      Because calibration was consistent with the certified results, this analytical
      method is a sensitive tool for analysis of environmental calcium carbonate
      matrices. Repeated analysis of scallop shell samples collected simultaneously at
      the same location showed that the trace elements are homogeneously distributed
      along a stria. The reliability of such in-situ records of biogenic calcium
      carbonate (scallop shells) is apparent from the inter-individual and inter-annual
      reproducibility of the trace element profiles.

PMID- 17200852
TI  - Time-resolved fluoroimmunoassay for ractopamine in swine tissue.
AB  - This study describes the development and validation of a time-resolved
      fluoroimmunoassay (TR-FIA) for screening ractopamine (RAC) in swine tissue. The
      method is based on the direct competitive-type immunoassay using europium-labeled
      anti-RAC monoclonal antibody as a tracer and RAC-ovalbumin as a solid-phase
      antigen. When RAC was spiked at levels of 1-10 microg kg(-1), recoveries ranged
      from 88.2 to 118.5% for swine liver and muscle with coefficients of variation
      from 7.1 to 20.5%. The detection limit was 0.1 microg kg(-1). The proposed TR-FIA
      method was applied to the determination of RAC in an actual residue study and the
      applicability was confirmed by liquid chromatography-tandem mass spectrometry.

PMID- 17200851
TI  - Immobilization of hemoglobin on SBA-15 applied to the electrocatalytic reduction
      of H2O2.
AB  - The direct electron transfer between hemoglobin (Hb) and an electrode was
      realized by first immobilizing the protein onto SBA-15. The results of the
      immobilization showed that the adsorption was pH-dependent with a maximum
      adsorption near the isoelectric point of the protein, and SBA-15 with a larger
      pore diameter showed greater adsorption capacity for Hb. UV-vis spectroscopy and
      nitrogen adsorption analysis indicated that Hb was adsorbed within the channel of
      SBA-15 and no significant denaturation occurred to the protein. The Hb/SBA-15
      composite obtained was used for the fabrication of a Hb biosensor to detect
      hydrogen peroxide. A pair of well-defined redox peaks at -0.337 and -0.370 V on
      the Hb/SBA-15 composite modified glassy carbon electrode was observed, and the
      electrode reactions showed a surface-controlled process with a single proton
      transfer at a scan rate range from 20 to 1,000 mV/s. The sensor showed a fast
      amperometric response, a low detection limit (2.3 x 10(-9) M) and good stability
      for the detection of H(2)O(2). The electrochemical results indicated that the
      immobilized Hb still retained its biological activity.

PMID- 17200853
TI  - Determination of organic additives in mortars by near-IR spectroscopy. A novel
      approach to designing a sample set with high-variability components.
AB  - Industrial mortars consist primarily of a mixture of cement and an aggregate plus
      a small amount of additives that are used to modify specific properties. Using
      too high or too low additive rates usually results in the loss of desirable
      properties in the end product. This entails carefully controlling the amounts of
      additives added to mortar in order to ensure correct dosing and/or adequate
      homogeneity in the final mixture. Near-IR (NIR) spectroscopy has proved effective
      for this purpose as it requires no sample pretreatment and affords expeditious
      analyses. The purpose of this work was to determine two organic additives (viz.
      Ad1 and Ad2) in mortars by using partial least squares regression multivariate
      calibration models constructed from NIR spectroscopic data. The additives are
      used to expedite setting and increase cohesion between particles in the mortar.
      In order to ensure that the sample set contained natural variability in the
      samples, we used a methodology based on experimental design to construct a
      representative set of samples. This novel design is based on a hexagonal
      antiprism that encompasses the concentration ranges spanned by the analytes and
      the variability inherent in each additive. The D-optimality criterion was used to
      obtain various combinations between Ad1 and Ad2 additive classes. The partial
      least squares calibration models thus constructed for each additive provided
      accurate predictions: the intercept and the slope of the plots of predicted
      values versus reference values for each additive were close to 0 and 1,
      respectively, and their confidence ranges included the respective value. The
      ensuing analytical methods were validated by using an external sample set.

PMID- 17200854
TI  - Desorption of BTEX from activated charcoal using accelerated solvent extraction:
      evaluation of occupational exposures.
AB  - A procedure for the determination of benzene, toluene, ethylbenzene and o-xylene,
      m-xylene and p-xylene (BTEX) in occupational environments is proposed. These
      compounds are extracted from activated charcoal using accelerated solvent
      extraction. Operational parameters are optimized and quantitative recovery is
      obtained using acetonitrile as the extraction solvent and 1-mL extraction cells,
      a preheat time of 2 min, a temperature of 160 degrees C, a pressure of 1,500 psi,
      a static period of 5 min, a flush volume of 110%, two cycles and a purge time of
      90 s. Determination of BTEX compounds is carried out by gas chromatography using
      a flame ionization detector. The recoveries, obtained for a confidence level of
      95%, are 91 +/- 4, 100 +/- 3, 104 +/- 2, 93 +/- 4, 99 +/- 2 and 99 +/- 2% for
      benzene, toluene, ethylbenzene, o-xylene, m-xylene and p-xylene, respectively.
      The detection limits are 0.5 microg for benzene, 0.7 microg for toluene and 1.0
      microg for the other compounds. The proposed procedure has been applied to real
      samples collected in several workplaces, like a microbiology laboratory, an
      analytical chemistry laboratory, a printer's, a car repair shop and a petrol
      station. From the results obtained, it can be concluded that the occupational
      exposures determined are always acceptable because they are lower than the tenth
      part of the recommended exposure limits (VLA-ED and VLA-EC).

PMID- 17200855
TI  - Electrocatalytic determination of reduced glutathione in human erythrocytes.
AB  - The determination of reduced glutathione (GSH) in human erythrocytes using a
      simple, fast and sensitive method employing a glassy carbon electrode modified
      with cobalt tetrasulfonated phthalocyanine (CoTSPc) immobilized in poly(L: 
      lysine) (PLL) film was investigated. This modified electrode showed very
      efficient electrocatalytic activity for anodic oxidation of GSH, decreasing
      substantially the anodic overpotentials for 0.2 V versus Ag/AgCl. The modified
      electrode presented better performance in 0.1 mol l(-1) piperazine-N,N'-bis(2
      ethanesulfonic acid) buffer at pH 7.4. The other experimental parameters, such as
      the concentration of CoTSPc and PLL in the membrane preparation, pH, type of
      buffer solution and applied potential, were optimized. Under optimized
      operational conditions, a linear response from 50 to 2,160 nmol l(-1) was
      obtained with a high sensitivity of 1.5 nA l nmol(-1) cm(-2). The detection limit
      for GSH determination was 15 nmol l(-1). The proposed sensor presented good
      repeatability, evaluated in terms of the relative standard deviation (1.5%) for n
      = 10. The modified electrode was applied for determination of GSH in erythrocyte
      samples and the results were in agreement with those obtained by a comparative
      method described in the literature The average recovery for these fortified
      samples was 100 +/- 1)%. Applying a paired Student's-t test to compare these
      methods, we could observe that, at the 95% confidence level, there was no
      statistical difference between the reference and the proposed methods.

PMID- 17200856
TI  - Comparison of multivariate calibration models for glucose, urea, and lactate from
      near-infrared and Raman spectra.
AB  - Partial least-squares (PLS) calibration models have been generated from a series
      of near-infrared (near-IR) and Raman spectra acquired separately from sixty
      different mixed solutions of glucose, lactate, and urea in aqueous phosphate
      buffer. Independent PLS models were prepared and compared for glucose, lactate,
      and urea. Near-IR and Raman spectral features differed substantially for these
      solutes, with Raman spectra enabling greater distinction with less spectral
      overlap than features in the near-IR spectra. Despite this, PLS models derived
      from near-IR spectra outperformed those from Raman spectra. Standard errors of
      prediction were 0.24, 0.11, and 0.14 mmol L(-1) for glucose, lactate, and urea,
      respectively, from near-IR spectra and 0.40, 0.42, and 0.36 mmol L(-1) for
      glucose, lactate, and urea, respectively, from Raman spectra. Differences between
      instrumental signal-to-noise ratios were responsible for the better performance
      of the near-IR models. The chemical basis of model selectivity was examined for
      each model by using a pure component selectivity analysis combined with analysis
      of the net analyte signal for each solute. This selectivity analysis showed that
      models based on either near-IR or Raman spectra had excellent selectivity for the
      targeted analyte. The net analyte signal analysis also revealed that analytical
      sensitivity was higher for the models generated from near-IR spectra. This is
      consistent with the lower standard errors of prediction.

PMID- 17200858
TI  - Characteristics of the Raman spectra of single-walled carbon nanotube bundles
      under electrochemical potential control.
AB  - Resonant Raman scattering spectra of single-walled carbon nanotube-sodium dodecyl
      sulfate (SWNT-SDS) bundles adsorbed on Au electrodes have been investigated in
      aqueous electrolytes. Raman intensities of the radial breathing mode (RBM) with
      785-nm laser excitation were monitored at different electrode potentials between 
      0.5 and +0.8 V relative to the SCE. Six resolved RBM peaks assignable to
      different diameter tubes all decreased in intensity when the electrode was
      positively biased, because of depletion of valence-band electrons associated with
      resonant excitation. The attenuation occurred at more positive potentials for
      narrower-diameter tubes with higher RBM frequencies consistent with their larger
      bandgaps. The results suggest the Fermi level is equilibrated in bundled SWNTs in
      contrast with the large Fermi-level shifts reported for isolated SWNTs.

PMID- 17200857
TI  - Polar herbicides, pharmaceutical products, perfluorooctanesulfonate (PFOS),
      perfluorooctanoate (PFOA), and nonylphenol and its carboxylates and ethoxylates
      in surface and tap waters around Lake Maggiore in Northern Italy.
AB  - A survey of contamination of surface and drinking waters around Lake Maggiore in
      Northern Italy with polar anthropogenic environmental pollutants has been
      conducted. The target analytes were polar herbicides, pharmaceuticals (including
      antibiotics), steroid estrogens, perfluorooctanesulfonate (PFOS), perfluoroalkyl
      carboxylates (including perfluorooctanoate PFOA), nonylphenol and its
      carboxylates and ethoxylates (NPEO surfactants), and triclosan, a bactericide
      used in personal-care products. Analysis of water samples was performed by solid
      phase extraction (SPE) then liquid chromatography-triple-quadrupole (tandem) mass
      spectrometry (LC-MS-MS). By extraction of 1-L water samples and concentration of
      the extract to 100 microL, method detection limits (MDLs) as low as 0.05-0.1 ng
      L(-1) were achieved for most compounds. Lake-water samples from seven different
      locations in the Southern part of Lake Maggiore and eleven samples from different
      tributary rivers and creeks were investigated. Rain water was also analyzed to
      investigate atmospheric input of the contaminants. Compounds regularly detected
      at very low concentrations in the lake water included: caffeine (max.
      concentration 124 ng L(-1)), the herbicides terbutylazine (7 ng L(-1)), atrazine
      (5 ng L(-1)), simazine (16 ng L(-1)), diuron (11 ng L(-1)), and atrazine-desethyl
      (11 ng L(-1)), the pharmaceuticals carbamazepine (9 ng L(-1)), sulfamethoxazole
      (10 ng L(-1)), gemfibrozil (1.7 ng L(-1)), and benzafibrate (1.2 ng L(-1)), the
      surfactant metabolite nonylphenol (15 ng L(-1)), its carboxylates (NPE(1)C 120 ng
      L(-1), NPE(2)C 7 ng L(-1), NPE(3)C 15 ng L(-1)) and ethoxylates (NPE( n )Os, n =
      3-17; 300 ng L(-1)), perfluorinated surfactants (PFOS 9 ng L(-1), PFOA 3 ng L(
      1)), and estrone (0.4 ng L(-1)). Levels of these compounds in drinking water
      produced from Lake Maggiore were almost identical with those found in the lake
      itself, revealing the poor performance of sand filtration and chlorination
      applied by the local waterworks.

PMID- 17200859
TI  - Application of support vector machines to 1H NMR data of fish oils: methodology
      for the confirmation of wild and farmed salmon and their origins.
AB  - Support vector machines (SVMs) were used as a novel learning machine in the
      authentication of the origin of salmon. SVMs have the advantage of relying on a
      well-developed theory and have already proved to be successful in a number of
      practical applications. This paper provides a new and effective method for the
      discrimination between wild and farm salmon and eliminates the possibility of
      fraud through misrepresentation of the country of origin of salmon. The method
      requires a very simple sample preparation of the fish oils extracted from the
      white muscle of salmon samples. (1)H NMR spectroscopic analysis provides data
      that is very informative for analysing the fatty acid constituents of the fish
      oils. The SVM has been able to distinguish correctly between the wild and farmed
      salmon; however ca. 5% of the country of origins were misclassified.

PMID- 17200860
TI  - Determination of nitrobenzene by differential pulse voltammetry and its
      application in wastewater analysis.
AB  - A new method for the determination of nitrobenzene (NB) by differential pulse
      voltammetry (DPV) based on an adsorptive stripping technique was developed.
      Cyclic voltammetry (CV) was used in a comparative investigation into the
      electrochemical reduction of NB at a glassy carbon electrode (GCE). With this
      electrode, the sharp peak of NB appeared at -0.71 V (vs. Ag/AgCl). The
      experimental parameters were optimized. Studies on the effect of pH on the peak
      height and peak potential were carried out over the pH range ca. 9.0-11.5 with
      sodium carbonate/sodium hydrogen carbonate buffer solution. A solution of pH 9.9
      was chosen as analytical medium. Cathodic peak currents were found to be linearly
      related to the concentration of NB over the range ca. 12.3-1.23 x 10(4) microg L(
      1) with relative standard deviations of ca. 3.26-6.75%. The detection limit of NB
      in water was 5.42 microg L(-1). The interference of organic and inorganic species
      on the voltammetric response was also studied. The proposed method was applied to
      the determination of NB in wastewater samples with an average recovery of ca.
      95.9-102.4%.

PMID- 17200861
TI  - Influence of structural factors on the enhanced activity of moxifloxacin: a
      fluorescence and EPR spectroscopic study.
AB  - Partition coefficients of moxifloxacin in liposomes of dimyristoyl-L-alpha
      phosphatidylcholine or dimyristoyl-L-alpha-phosphatidylglycerol and water were
      determined by spectrophotometry and fluorimetry. The K (p) values obtained were
      larger than those reported for most of the other fluoroquinolones, a consequence
      of the structural changes observed in the molecule of moxifloxacin, which in turn
      change its acid/base properties. Introduction of a methoxy group at position 8
      and a diazabicyclonyl ring at position 7 in the basic fluoroquinolone structure
      alters the charge distribution at the physiological pH of 7.4, and these changes
      seem to be responsible for its improved antibacterial potency and broader
      spectrum of activity. Location studies have also been performed using
      fluorescence and electron paramagnetic resonance (EPR) spectroscopies. The
      results show that moxifloxacin must be located near the phospholipid headgroups,
      similar to other fluoroquinolones, but contributions from a hydrophobic component
      were also detected. These results suggest that the enhanced activity of this drug
      may be related to a more facilitated entrance into the bacterial cell, perhaps
      including a mediator step involving electrostatic interaction with a hydrophobic
      component; this step then controls the extent or orientation of insertion and
      improves the electrostatic interaction.

PMID- 17200862
TI  - Interaction of nucleoside diphosphate kinase B with heterotrimeric G protein
      betagamma dimers: consequences on G protein activation and stability.
AB  - It is generally accepted that G protein coupled receptors (GPCR) activate
      heterotrimeric G proteins by inducing a GDP/GTP exchange at the G protein alpha
      subunit. In addition, the transfer of high energetic phosphate by nucleoside
      diphosphate kinase (NDPK) and/or the beta subunit of G proteins (Gbeta) can
      induce G protein activation. Recent evidence suggests that the NDPK isoform B
      (NDPK B) forms a complex with Gbetagamma dimers. In this complex, NDPK B acts as
      a protein histidine kinase phosphorylating Gbeta at histidine residue 266
      (His266). The high energetic phosphoamidate bond on His266 allows for a phosphate
      transfer specifically onto GDP and thus local formation of GTP, which binds to
      and thereby activates the respective G protein alpha subunit. Apparently, this
      process occurs independent of the classical GPCR-induced GDP/GTP exchange at
      least for members of the G(s) and G(i) subfamilies of heterotrimeric G proteins.
      By using a mutant of Gbeta(1) in which His266 was replaced by Leu, it was
      recently demonstrated that NDPK B/Gbetagamma-mediated G(s) activation contributes
      by about 50% to basal cAMP formation and contractility in rat cardiac myocytes.
      Besides its apparent role in G protein activation, the complex formation of NDPK
      B with Gbetagamma dimers might be essential for G protein stability. Depletion of
      either the NDPK B orthologue or Gbeta(1) isoforms in zebrafish embryos led to a
      similar phenotype displaying contractile dysfunction in the heart accompanied by
      a complete loss of heterotrimeric G protein expression. In conclusion, the
      interaction of NDKP B with Gbetagamma dimers might play an important role in
      signal transduction, and alterations in this novel pathway might be of
      pathophysiological importance.

PMID- 17200863
TI  - Evaluation of pituitary macroadenomas with multidetector-row CT (MDCT):
      comparison with MR imaging.
AB  - INTRODUCTION: It is important to have information on cavernous sinus extension
      and bony destruction in pituitary macroadenomas before surgery, but magnetic
      resonance (MR) imaging cannot always depict them. In the present study we sought
      to determine whether multidetector-row computed tomography (MDCT) could provide
      preoperative information in addition to that provided by MR imaging in pituitary
      macroadenoma. METHODS: The subjects comprised 33 consecutive patients (15 women,
      18 men; mean age 50 years) with surgically proven macroadenoma. For MDCT, using
      the soft-tissue window and bone window, three orthogonal multiplanar
      reconstruction images were generated from venous-phase contrast-enhanced 0.5-mm
      isotropic voxel data. MDCT and MR images were evaluated with regard to: (1)
      clarity of tumor margins; (2) identification of the normal pituitary gland; (3)
      identification of erosion or destruction of the sellar floor; and (4)
      visualization of the adjacent optic pathways. RESULTS: MDCT more clearly
      demonstrated the lateral tumor margin than MR imaging (P = 0.002). No significant
      differences in visualization of the normal pituitary gland were noted between
      MDCT and dynamic MR imaging (P = 0.7). MDCT more clearly demonstrated sellar
      floor erosion or destruction at the sphenoid sinus than MR imaging (P < 0.001).
      MR imaging was superior to MDCT for visualizing the adjacent optic pathways (P <
      0.001). CONCLUSION: MDCT is superior to MR imaging for assessing lateral tumor
      margin and the sellar floor at the sphenoid sinus. MDCT offers useful
      preoperative information in addition to that obtained from MR imaging.

PMID- 17200864
TI  - Perfusion MRI before and after acetazolamide administration for assessment of
      cerebrovascular reserve capacity in patients with symptomatic internal carotid
      artery (ICA) occlusion: comparison with 99mTc-ECD SPECT.
AB  - INTRODUCTION: Impaired cerebral vascular reserve (CVR) in patients with
      symptomatic internal carotid artery (ICA) occlusion is regarded as a possible
      indication for performing extra-/intracranial (EC/IC) bypass surgery. As
      perfusion MR imaging (MRI) can demonstrate cerebral haemodynamics at capillary
      level, our hypothesis was that perfusion MRI could be used in these patients for
      the evaluation of CVR following acetazolamide challenge in a similar way to
      single photon emission CT (SPECT) and might provide additional information.
      METHODS: Enrolled in the study were 12 patients (mean age 61.3 years; 11 male, 1
      female) with symptomatic unilateral ICA occlusion proven by angiography. Both
      perfusion MRI and 99m-technetium-ethyl-cysteinate dimer ((99m)Tc-ECD) SPECT were
      performed before and after injection of acetazolamide (Diamox ,1000 mg i.v.). CVR
      parameters including regional cerebral blood flow (rCBF) and volume (rCBV), and
      mean transit times (MTT) were measured by perfusion MRI. RESULTS: The patients
      with impaired CVR proven by SPECT (n = 9) had a negative mean rCBF increment (
      46.52%), negative rCBV increment (-13.5%) and delayed MTT (mean +2.98 s),
      respectively, on the occluded side (Student's t-test all P < 0.05). The patients
      with sufficient CVR (n = 3) had a mean rCBF increment of 1.2%, a decrement of
      rCBV of 10.46%, and a mean MTT shortening of 0.27 s following the acetazolamide
      injection. CONCLUSIONS: Perfusion MRI before and after acetazolamide
      administration compares favourably with (99m)Tc-ECD SPECT for the detection of
      impaired CVR. The impact that perfusion MRI studies (before and after
      acetazolamide administration) might have on the treatment decision in patients
      with ICA occlusion has yet to be determined by a prospective study.

PMID- 17200865
TI  - Focal neuronal loss, reversible subcortical focal T2 hypointensity in seizures
      with a nonketotic hyperglycemic hyperosmolar state.
AB  - INTRODUCTION: Neuroimaging in seizures associated with nonketotic hyperglycemia
      (NKH) is considered normal. We report magnetic resonance imaging (MRI)
      abnormalities in four patients with NKH and seizures. METHODS: We prospectively
      evaluated clinical and radiological abnormalities in four patients with NKH
      during the period March 2004 to December 2005. RESULTS: All patients presented
      with seizures, either simple or complex partial seizures or epilepsia partialis
      continua. Two of them had transient hemianopia. MRI showed subcortical T2
      hypointensity in the occipital white matter and in or around the central sulcus
      (two patients each), T2 hyperintensity of the overlying cortex (two patients),
      focal overlying cortical enhancement (three patients) and bilateral striatal
      hyperintensity (one patient). Diffusion-weighted imaging (DWI) performed in three
      patients showed restricted diffusion. The ictal semiology and
      electroencephalographic (EEG) findings correlated with the MRI abnormalities. On
      clinical recovery, the subcortical T2 hypointensity and striatal hyperintensity
      reversed in all patients. The initial cortical change evolved to FLAIR
      hyperintensity suggestive of focal cortical gliosis. The radiological
      differential diagnosis considered initially included encephalitis, malignancy and
      hemorrhagic infarct rendering a diagnostic dilemma. CONCLUSION: We identified
      subcortical T2 hypointensity rather than hyperintensity as a characteristic
      feature of seizures associated with NKH. Only very few similar reports exist in
      literature. Reversible bilateral striatal T2 hyperintensity in NKH has not been
      reported to the best of our knowledge.

PMID- 17200867
TI  - The dural entrance of cerebral bridging veins into the superior sagittal sinus:
      an anatomical comparison between cadavers and digital subtraction angiography.
AB  - INTRODUCTION: Intracranial venous structures have received increasing attention
      due to improved neuroimaging techniques and increased awareness of cerebral
      venous disease. To date, few studies have attempted to investigate the dural
      entrance of the cerebral bridging vein (BV). The aim of this study was to use the
      superior sagittal sinus (SSS) as an example to identify anatomical features of
      the dural entrance of the BVs into the SSS in both human cadavers and digital
      subtraction angiography (DSA) images. METHODS: A total of 30 adult and 7 fetal
      human cadavers and 36 patients were examined with anatomical dissections,
      vascular casting and DSA. The number, diameter and angle of the BVs entering the
      SSS were measured and compared between the cadavers and DSA images. RESULTS: The
      results demonstrated that (1) the way a BV entered the SSS varied in three
      dimensions, and thus the BV dural entrance was difficult to precisely localize by
      DSA, (2) the distribution pattern of the dural entrance of the BVs into the SSS
      was relatively constant and a nontributary segment of the SSS was centered at the
      coronal suture and was identifiable by DSA, and (3) nearly all the BVs (97%,
      561/581) entered the SSS at an angle opposite to the direction of blood flow.
      CONCLUSION: Unique anatomical features of the dural entrance of a BV into the SSS
      should be considered in neuroimaging interpretation of the sinus and its
      associated veins.

PMID- 17200866
TI  - Statistical parametric mapping and statistical probabilistic anatomical mapping
      analyses of basal/acetazolamide Tc-99m ECD brain SPECT for efficacy assessment of
      endovascular stent placement for middle cerebral artery stenosis.
AB  - INTRODUCTION: Statistical parametric mapping (SPM) and statistical probabilistic
      anatomical mapping (SPAM) were applied to basal/acetazolamide Tc-99m ECD brain
      perfusion SPECT images in patients with middle cerebral artery (MCA) stenosis to
      assess the efficacy of endovascular stenting of the MCA. METHODS: Enrolled in the
      study were 11 patients (8 men and 3 women, mean age 54.2 +/- 6.2 years) who had
      undergone endovascular stent placement for MCA stenosis. Using SPM and SPAM
      analyses, we compared the number of significant voxels and cerebral counts in
      basal and acetazolamide SPECT images before and after stenting, and assessed the
      perfusion changes and cerebral vascular reserve index (CVRI). RESULTS: The
      numbers of hypoperfusion voxels in SPECT images were decreased from 10,083 +/-
      8,326 to 4,531 +/- 5,091 in basal images (P = 0.0317) and from 13,398 +/- 14,222
      to 7,699 +/- 10,199 in acetazolamide images (P = 0.0142) after MCA stenting. On
      SPAM analysis, the increases in cerebral counts were significant in acetazolamide
      images (90.9 +/- 2.2 to 93.5 +/- 2.3, P = 0.0098) but not in basal images (91 +/-
      2.7 to 92 +/- 2.6, P = 0.1602). The CVRI also showed a statistically significant
      increase from before stenting (median 0.32; 95% CI -2.19-2.37) to after stenting
      (median 1.59; 95% CI -0.85-4.16; P = 0.0068). CONCLUSION: This study revealed the
      usefulness of voxel-based analysis of basal/acetazolamide brain perfusion SPECT
      after MCA stent placement. This study showed that SPM and SPAM analyses of
      basal/acetazolamide Tc-99m brain SPECT could be used to evaluate the short-term
      hemodynamic efficacy of successful MCA stent placement.

PMID- 17200869
TI  - Tracking the neurodegeneration of parkinsonian disorders--a pilot study.
AB  - The purpose of the study was to explore the possibilities of using diffusion
      tensor imaging (DTI) and tractography (DTT) for the differential diagnosis and
      monitoring of disease progression in idiopathic Parkinson's disease (IPD),
      compared with the atypical parkinsonian disorders multiple system atrophy (MSA)
      and progressive supranuclear palsy (PSP). A 3.0-T MR scanner was used. DTI was
      acquired using a single-shot EPI sequence with diffusion encoding in 32
      directions and a voxel size of 2 x 2 x 2 mm3. DTI data were analysed and DTT was
      performed using the PRIDE fibre tracking tool supplied by the manufacturer. The
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC) within each
      tract were determined. DTI and DTT images in patients with moderate to advanced
      MSA demonstrated degeneration of the middle cerebellar peduncles and pontine
      crossing tracts, with decreased FA and increased ADC. This accounted for most of
      the pontine and cerebellar atrophy characteristic of this disease. In contrast,
      patients with PSP showed a selective degeneration of the superior cerebellar
      peduncle. Three-dimensional images of whole-brain white matter tracts
      demonstrated a reduction of cortical projection fibres in all patients with PSP.
      Visualization of the selective degeneration of individual fibre tracts, using DTI
      and DTT, adds qualitative data facilitating the differential diagnosis of
      parkinsonian disorders. Repeated measurements of FA and ADC values in a whole
      fibre tract might be used for monitoring disease progression and studying the
      effect of treatment in neuroprotective trials. The results are preliminary
      considering the small number of subjects in the study.

PMID- 17200868
TI  - Endovascular treatment of intracranial aneurysms with matrix coils: immediate
      posttreatment results, clinical outcome and follow-up.
AB  - INTRODUCTION: Endovascular aneurysm repair with coils has become a safe and
      effective alternative to surgical clipping. Efforts have been made to create
      coils that will facilitate aneurysm healing and reduce recurrence. The purpose of
      this study was to review the safety and durability of our aneurysm treatment
      using Matrix coils. METHODS: A total of 39 aneurysms in 38 patients, aged 30 to
      77 years, were treated using Matrix coils in 42 procedures. Two procedures were
      unsuccessful, and 12 were done using only Matrix coils. Aneurysm volume, packing
      density and percentage length of Matrix coils were calculated. The treatment
      results, procedural complication rate and clinical outcome were analyzed. Follow
      up examinations were available for 34 procedures with a mean follow-up of 4.9
      months (maximum 13.5 months). RESULTS: Angiographic results were similar to those
      following the use of platinum coils, with complete occlusion or a residual neck
      in 82.5% of procedures. Six procedures (14%) were complicated with platelet
      aggregation. Recanalization occurred in 32% of the patients. Nine patients (26%)
      had major recanalization and were retreated. One patient had a re-bleed 5 months
      after the treatment resulting in severe disability. The mean packing density of
      39.2% in the recanalized aneurysms was similar to that in the nonrecanalized
      group. CONCLUSION: In our series, treatment with Matrix coils had a complication
      rate similar to that reported with platinum coils. However, we had a higher
      percentage of major recanalizations requiring retreatment. We believe that the
      absorption of the polymer contributes to the failure of formation of a stable
      scar within the aneurysm.

PMID- 17200871
TI  - KIR haplotype content at the allele level in 77 Northern Irish families.
AB  - There has been an explosion in population studies determining the frequency of
      KIR genes. However, there is still limited knowledge of allele and haplotype
      frequencies in different populations. The present study aims to determine the
      haplotype frequencies using allele information on ten genes and presence/absence
      of the other seven genes in the parents of 77 families. There were 26 of 154
      different genotypes without using allele information and 143 of 154 different
      genotypes using allele information. These genotypes came from 96 of 308 different
      haplotypes. Of these, 41 were A and 55 were B. Forty-nine haplotypes occurred
      only once. In total, 181 (58.8%) of haplotypes were A and 127 (41.2%) were B.
      Three different haplotypes carried two copies of KIR2DL4, two different
      haplotypes were truncated with both KIR2DL4 and KIR3DL1/S1 missing, and three
      different haplotypes were negative for both KIR2DL2 and KIR2DL3; two of these
      haplotypes carried KIR2DS2. A further haplotype, present in two individuals,
      appeared to have two alleles of KIR2DL5A present. The percentages of individuals
      who were homozygous for the A haplotype, heterozygous for the A and B haplotype
      and homozygous for the B haplotype were 35.1%, 47.4% and 17.5% respectively. The
      genes KIR3DL1, KIR2DS4 and KIR2DL3 were present on 31, 32 and 15 different B
      haplotypes, respectively, and 64, 65 and 40 of the total B haplotypes,
      respectively. Sixty B haplotypes had both KIR3DL1 and KIR2DS4, and four
      haplotypes had KIR2DS4 and KIR2DL3. However, in 40 of 41 different and 180 of 181
      total A haplotypes, KIR3DL1, KIR2DS4 and KIR2DL3 were all present (we did not
      allele-type for KIR2DL1 and therefore could not determine presence/absence on
      those haplotypes). At the allele level, homozygosity was found in 22.1%, 9.7% and
      12.6% for KIR2DL4, KIR3DL2 and KIR3DL1 genes, respectively, but 62.6% and 53% for
      KIR2DL3 and KIR2DS4 genes, respectively, despite the fact that no one allele
      dominated the frequency in any of these genes.

PMID- 17200870
TI  - Mapping of susceptibility and protective loci for acute GVHD in unrelated HLA
      matched bone marrow transplantation donors and recipients using 155
      microsatellite markers on chromosome 22.
AB  - Despite matching donors and recipients for the human leukocyte antigens (HLAs)
      expressed by the major histocompatibility genomic region of the short arm of
      chromosome 6, several recipients still develop acute graft-versus-host disease
      (aGVHD) after bone marrow transplantation (BMT). This is possibly due to non-HLA
      gene polymorphisms, such as minor histocompatibility antigens (mHas) and genes
      coding for cytokines. However, a detailed genetic background for aGVHD has not
      yet been established. To find novel susceptibility and/or protective loci for
      aGVHD, a whole genome-wide association study of donors and recipients needs to be
      performed. As the first step to such a study, we retrospectively analyzed
      polymorphisms of 155 microsatellite markers spread across the long arm of
      chromosome 22 in 70 pairs of HLA-matched unrelated BMT donors and recipients. We
      performed individual typing and then compared the markers' allele frequencies (1)
      between all the aGVHD (grades III and IV GVHD) and GVHD-free (grade 0 GVHD)
      groups in donors and recipients and (2) between the aGVHD and aGVHD-free groups
      in donor/recipient pairs that were matched and mismatched for the microsatellite
      marker's allele. Screening of the microsatellite markers revealed five loci with
      a significant difference between the aGVHD and GVHD-free groups and revealed
      eight loci on chromosome 22, where the microsatellite allele mismatched markers
      were associated with aGVHD. This screening analysis suggests that several aGVHD
      associated susceptible and protective loci exist on chromosome 22, which may
      encompass novel gene regions that need to be elucidated for their role in aGVHD.

PMID- 17200874
TI  - Transmission of violent offending and crime across three generations.
AB  - BACKGROUND: We previously reported 24-fold risk (OR) of violent crime and 17-fold
      risk for criminal offending among adult children of homicide recidivistic
      offenders (HR). However, there exist neither published data on the quantitative
      risk for crime or violent offending among parents of violent offenders, nor data
      on the transmission of the increased prevalence of crime across three
      generations. METHODS: In this naturalistic case-control cohort study all HR
      subjects (G2, n = 35) were extracted from the total of 1584 homicide offenders
      who were convicted in Finland during 1981-1993. The criminal records and prison
      documents from their parents (G1, n = 68), and the matched controls (n = 136),
      were studied, and compared with the previously published data from their children
      (G3, n = 11) and the controls (n = 220). RESULTS: Among the G1 parents of HR, the
      odds ratio (OR) for committing any crime was 5.0 (95% CI = 1.3-23.1) but the risk
      for violent offending was not significantly increased (OR = 3.1, 95% CI = 0.3
      37.6). The prevalence of index persons convicted for any crime (versus controls)
      was 13.2% (versus 2.9%) in G1 and 36.4% (versus 3.2%) in G3. Only 4.4% (versus
      1.5%) of G1 index parents, as compared to 18.2% (versus 0.9%) of G3 had
      convictions for violent crimes. The disparity of the proportions of criminal
      offenders between index versus control groups had increased across generations (P
      = 0.0023). This was also the case with violent offenders (P = 0.0019).
      CONCLUSIONS: The homicide recidivistic offenders had parents with 5-fold risk for
      any crime but, without significant risk for violent offending. The results
      provide the first evidence of transmission of crime across three generations, and
      also of the increased risk of crime among parents of violent offenders.

PMID- 17200872
TI  - Vitamin B6 deficiency augments endogenous oxalogenesis after intravenous L
      hydroxyproline loading in rats.
AB  - The effects of an intravenous hydroxyproline load on endogenous oxalogenesis were
      compared in rats fed a standard diet or a vitamin B6-deficient diet. Twelve male
      Wistar rats were randomized to two groups and were fed either a standard diet
      (control group) or a vitamin B6-deficient diet for 3 weeks. Then the animals were
      intravenously administered 100 mg (762.6 micromol)/ml hydroxyproline. In the
      control group, infusion of hydroxyproline increased the 5-h urinary oxalate and
      glycolate excretion above baseline to 0.27% (2.02 +/- 1.11 micromol) and 0.32%
      (2.43 +/- 1.60 micromol) of the administered dose (mol/mol), while it was
      respectively 2.01% (15.24 +/- 2.13 micromol) and 0.00% (-0.02 +/- 0.19 micromol)
      of the dose in the vitamin B6-deficient group. Therefore, vitamin B6 deficiency
      augmented endogenous synthesis of oxalate from hydroxyproline by 7.56-fold
      (15.24/2.02) compared with that in the control group. Urinary citrate excretion
      was significantly lower at baseline and all other times in the vitamin B6
      deficient group compared with the control group. In conclusions, L-hydroxyproline
      loading augmented endogenous oxalogenesis in the vitamin B6-deficient group
      without causing hyperglycolic aciduria, and also led to significant
      hypocitraturia. These findings suggest that hydroxyproline is not metabolized to
      oxalate via glycolate, but rather via the 4-hydroxyglutamate to glyoxylate
      pathway (usually requiring vitamin B6-dependent enzymes) even in the presence of
      vitamin B6 deficiency.

PMID- 17200877
TI  - The current state of mental health care in Italy: problems, perspectives, and
      lessons to learn.
AB  - After legislative changes in 1978, Italian psychiatry underwent a thorough
      overhaul, with the gradual closure of all Mental Hospitals. A nation-wide network
      of Departments of Mental Health now deliver outpatient and inpatient care, but
      also run semi-residential and residential facilities (the latter with 2.9 beds
      per 10,000 inhabitants). Hospital care is delivered through small psychiatric
      units (with no more than 15 beds). There are also many private inpatient
      facilities operating in Italy, and the number of private inpatient beds per
      10,000 inhabitants exceeds the number of public beds; overall there are 1.7 acute
      beds per 10,000 inhabitants - one of Europe's currently lowest numbers. There is
      marked quanti- and qualitative variation in the provision of out- and inpatient
      care throughout the country, and service utilization patterns are similarly
      uneven. Studies examining quality of life report a fairly high degree of patient
      satisfaction, whereas patients' families frequently bear a heavy burden. In
      conclusion, the Italian reform law led to the establishment of a broad network of
      facilities to meet diverse care needs. Further efforts are required to improve
      quality of care and to develop a more effectively integrated system. Greater
      attention must be paid to topics such as quality of care and outcomes, public and
      private sector balance, and the coordination of various resources and agencies.

PMID- 17200875
TI  - Effect of the olive oil phenol hydroxytyrosol on human hepatoma HepG2 cells.
      Protection against oxidative stress induced by tert-butylhydroperoxide.
AB  - BACKGROUND: Scientific evidence suggests that olive oil's beneficial effects are
      related to the high level of antioxidants, including phenolic compounds such as
      hydroxytyrosol. In vivo studies have shown that olive oil HTy is bioavailable and
      its biological activities, similar to those reported for other natural
      antioxidants such as quercetin, include prevention of LDL oxidation. Previous
      studies from our laboratory have shown that HTy and other phenolics in olive oil
      are absorbed and metabolized by cultured human hepatoma HepG2 cells where
      glucuronidated and methylated conjugates were the main derivatives formed,
      resembling the metabolic profile of olive oil phenols observed in human plasma
      and urine. AIM OF THE STUDY: The effect of olive oil phenol (HTy) on cell
      viability and redox status of cultured HepG2 cells, and the protective effect of
      HTy against an oxidative stress induced by tertbutylhydroperoxide (t-BOOH) were
      investigated. METHODS: Lactate dehydrogenase activity as marker for cell
      integrity, concentration of reduced glutathione (GSH), generation of reactive
      oxygen species (ROS) and activity of the antioxidant enzyme glutathione
      peroxidase (GPx) as markers of redox status and determination of malondialdehyde
      (MDA) as marker of lipid peroxidation were measured. RESULTS: No changes in cell
      integrity or intrinsic antioxidant status resulted from a direct treatment with
      10-40 microM HTy. Pre-treatment of HepG2 with 10-40 microM HTy for 2 or 20 h
      completely prevented cell damage as well as the decrease of reduced glutathione
      and increase of malondialdehyde evoked by t-BOOH in HepG2 cells. Reactive oxygen
      species generation and the significant increase of glutathione peroxidase
      activity induced by t-BOOH were greatly reduced when cells were pretreated with
      HTy. CONCLUSION: The results clearly show that treatment of HepG2 cells with the
      olive oil phenolic HTy may positively affect their antioxidant defense system,
      favoring cell integrity and resistance to cope with a stressful situation.

PMID- 17200878
TI  - Adult mental health care in England.
AB  - The policy background and current overall provision of mental health services for
      working age and older adults in England are described. Following the introduction
      of a new National Service Framework in 1999, an annual service mapping exercise
      was introduced. Data presented draw heavily on the mapping for 2003. This is
      supplemented by hospital admission statistics data from the new patient-based
      mental health minimum data set, introduced from April 2003, and a number of other
      corroborative sources. Data about services for older people are more restricted
      in scope and detail. Close attention is given to the extent to which data from
      these routine sources can be considered accurate.

PMID- 17200876
TI  - Long-term consumption of fermented soybean-derived Chungkookjang enhances
      insulinotropic action unlike soybeans in 90% pancreatectomized diabetic rats.
AB  - BACKGROUND: We previously reported that Chungkookjang (CKJ), fermented unsalted
      soybeans, exhibited better anti-diabetic action than cooked soybeans (CSB) in
      vitro, but its effectiveness and mechanism have not been studied in vivo. AIM OF
      THE STUDY: We investigated whether CKJ modulated insulin resistance, insulin
      secretion, and pancreatic beta-cell growth and survival in 90% pancreatectomized
      (Px) diabetic rats. METHODS: The Px rats weighing 201 +/- 12 g were divided into
      four groups and fed for 8 weeks with a CSB diet, a CKJ diet, a casein diet, or a
      casein diet plus rosiglitazone (20 mg/kg body weight/day). With the exception of
      protein sources and contents of isoflavonoid aglycones and glycosides, the
      composition of the diets was made identical by adding soybean oil and cellulose
      to a casein diet. At the end of the experimental periods, hyperglycemic clamp was
      performed in conscious, unstressed and overnight fasted Px rats to measure
      insulin secretion capacity. Insulin/IGF-1 signaling was measured by
      immunoblotting in isolated islets from the treated rats, and beta-cell mass,
      proliferation and apoptosis were also determined by immunohistochemistry.
      RESULTS: After 8-week administration, CSB did not modulate glucose-stimulated
      insulin secretion, but surprisingly, CKJ enhanced insulin secretion. In addition,
      CKJ potentiated insulin/IGF-1 signaling in islets via the induction of insulin
      receptor substrate-2 expression, leading to increasing pancreatic duodenal
      homeobox-1, insulin promoter transcription factor. In parallel with the
      enhancement of the signaling, CKJ elevated pancreatic beta-cell hyperplasia by
      increasing its proliferation and decreasing apoptosis, whereas CSB did not.
      CONCLUSION: Based on these results, the fermentation of soybeans predominantly
      with Bacillus subtilis generated isoflavonoid aglycones and small peptides, which
      improved insulinotropic action in islets of type 2 diabetic rats. Overall, the
      anti-diabetic action of CKJ was superior to CSB in type 2 diabetic rats.

PMID- 17200879
TI  - Neuropsychological assessment of adult patients with attention
      deficit/hyperactivity disorder.
AB  - Adults with persistent attention-deficit/hyperactivity disorder (ADHD) may show
      cognitive deficits as compared to healthy control subjects. The aim of this study
      was to compare a sample of adult outpatients with ADHD on medication to healthy
      controls on a comprehensive neuropsychological assessment battery. Thirty adults
      with ADHD under stable psychopharmacological treatment and 27 healthy controls
      matched for age, gender, and IQ were assessed with ten tests measuring
      performance with regard to attention, memory, executive function, and fine motor
      control. Lower performance in patients as compared to controls was found in tests
      of verbal and visual memory, speed of visuo-motor search, set shifting, and
      divided attention. Indicators of response inhibition and simple response speed
      were less affected. Adults with ADHD show indicators of lowered cognitive
      performance under medication. These are related more to memory and attention
      under high mental load than to response inhibition or simple attention or motor
      performance.

PMID- 17200882
TI  - Nanoscopic and redox characterization of engineered horse cytochrome C
      chemisorbed on a bare gold electrode.
AB  - In this paper, we exploit the potential offered by site-directed mutagenesis to
      achieve direct adsorption of horse cyt c on a bare gold electrode surface. To
      this issue, the side chain T102 has been replaced by a cysteine. T102 is close to
      the surface exposed C-terminal residue (E104), therefore the T102C mutation is
      expected to generate an exposed cysteine side chain able to facilitate protein
      binding to the electrode via the sulphur atom (analogously to what observed for
      yeast iso-1-cyt c). Scanning Tunnelling and Tapping Mode Atomic Force Microscopy
      measurements show that the T102C mutant stably adsorbs on an Au(111) surface and
      retains the morphological characteristics of the native form. Cyclic voltammetry
      reveals that the adsorbed variant is electroactive; however, the heterogeneous
      electron transfer with the electrode surface is slower than that observed for
      yeast iso-1-cyt c. We ascribe it to differences in the tertiary architecture of
      the two proteins, characterized by different flexibility and stability. In
      particular, the region where the N- and C-terminal helices get in contact (and
      where the mutation occurs) is analyzed in detail, since the interactions between
      these two helices are considered crucial for the stability of the overall protein
      fold.

PMID- 17200883
TI  - Effect of nicking the C-terminal region of the Clostridium botulinum serotype D
      neurotoxin heavy chain on its toxicity and molecular properties.
AB  - A unique strain of Clostridium botulinum serotype D 4947 produces toxin complexes
      that are composed of un-nicked components, including a neurotoxin (BoNT) and
      auxiliary proteins. This BoNT showed aberrant elution upon Superdex gel
      filtration, indicating a much lower molecular weight, due to hydrophobic
      interaction with the column. Limited trypsin proteolysis of BoNT produces two
      nicks; first nick yielded a BoNT 50 kDa light chain disulfide linked to a 100 kDa
      heavy chain (Hc), and a second nick arose in Hc C-terminal 10 kDa. The second
      nick occurred in the putative binding domain of the BoNT molecule and induced
      alterations in its secondary structure, leading to a significant reduction of
      mouse toxicity in comparison with that of the fully-activated singly nicked BoNT.
      These results help to clarify the role of the C-terminal half of the Hc in the
      oral toxicity of single-chain and more complex forms of BoNT.

PMID- 17200881
TI  - The extrinsic proteins of Photosystem II.
AB  - Years of genetic, biochemical, and structural work have provided a number of
      insights into the oxygen evolving complex (OEC) of Photosystem II (PSII) for a
      variety of photosynthetic organisms. However, questions still remain about the
      functions and interactions among the various subunits that make up the OEC. After
      a brief introduction to the individual subunits Psb27, PsbP, PsbQ, PsbR, PsbU,
      and PsbV, a current picture of the OEC as a whole in cyanobacteria, red algae,
      green algae, and higher plants will be presented. Additionally, the role that
      these proteins play in the dynamic life cycle of PSII will be discussed.

PMID- 17200880
TI  - Current status of the role of Cl(-) ion in the oxygen-evolving complex.
AB  - This minireview summarizes the current state of knowledge concerning the role of
      Cl(-) in the oxygen-evolving complex (OEC) of photosystem II (PSII). The model
      that proposes that Cl(-) is a Mn ligand is discussed in light of more recent
      work. Studies of Cl(-) specificity, stoichiometry, kinetics, and retention by
      extrinsic polypeptides are discussed, as are the results that fail to detect Cl(
      ) ligation to Mn and results that show a lack of a requirement for Cl(-) in PSII
      catalyzed H(2)O oxidation. Mutagenesis experiments in cyanobacteria and higher
      plants that produce evidence for a correlation between Cl(-) retention and stable
      interactions among intrinsic and extrinsic polypeptides are summarized, and
      spectroscopic data on the interaction between PSII and Cl(-) are discussed.
      Lastly, the question of the site of Cl(-) action in PSII is discussed in
      connection with the current crystal structures of the enzyme.

PMID- 17200885
TI  - Modelling neural informational propagation and functional auditory sensory memory
      with temporal multi-scale operators.
AB  - In this paper we prove that both diffusion and the leaky integrators cascade
      based transport mechanisms have as their inherent property the effect of temporal
      multi-scaling. The two transport mechanisms are modeled not as convolution based
      algorithms but as causal physical processes. This implies that propagation of
      information through a neural map may act as a mechanism for achieving temporal
      multi-scale analysis in the auditory system. Specifically, we are interested in
      the effects of such a transport process on the formation and the dynamics of
      auditory sensory memory. Two temporal models of information propagation are
      discussed and compared in terms of their ability to model auditory sensory memory
      effects and the biological plausibility of their structure: the causal diffusion
      based operator (CD) and the leaky integrator cascade based operator (LINC). We
      show that temporal multi-scale representations achieved by both models exhibit
      the effects similar to those of auditory sensory memory (filtering, time delay
      and binding of information). As regards higher-level functions of auditory
      sensory memory such as change detection, the LINC operator seems to be a
      biologically more plausible solution for modeling temporal cortical processing.

PMID- 17200884
TI  - Enzymatic properties of newly found green turtle egg white ribonuclease.
AB  - Egg white ribonuclease was first found in green turtle eggs. The general
      properties were studied on substrate specificity, the optimum pH and temperature,
      and the effect of pH and temperature on the RNase activity. The enzyme studied
      was specific for poly (C) and degraded poly (U) at the lower rate and had the pH
      optimum at 7.0 and the optimum temperature at 40 degrees C. It was stable at
      alkaline range (pH 8.0-10.0) and up to 60 degrees C in pH 9.0 for 1 h, and
      unstable at acidic side for all temperatures. All of the properties studied
      showed similarity to RNase A. However, the optimum pH, broad range of optimum
      temperature and pH stability were different from RNase A. To evaluate the
      relationship of the structure and enzymatic properties, the 3D-structure of this
      enzyme was engineered by program MODELLER using two RNases (2BWL and 2BLZ) as
      starting models. The differences found in activity might be affected from the
      structure of micro environmental changing caused by amino acids deletion and
      substitution on the molecule.

PMID- 17200886
TI  - Simulation of high-frequency sinusoidal electrical block of mammalian myelinated
      axons.
AB  - High frequency alternating current (HFAC) sinusoidal waveforms can block
      conduction in mammalian peripheral nerves. A mammalian axon model was used to
      simulate the response of nerves to HFAC conduction block. Sinusoidal waveforms
      from 1 to 40 kHz were delivered to eight simulated axon diameters ranging from
      7.3 to 16 microm. Conduction block was obtained between 3 to 40 kHz. The minimum
      peak to peak current at which block was obtained, defined as the block threshold,
      increased with increasing frequency. Block threshold varied inversely with axon
      diameter. Upon initiation, the HFAC waveform produced one or more action
      potentials. These simulation results closely parallel previous experimental
      results of high frequency motor block of the rat sciatic and cat pudendal nerve.
      During HFAC block, the axons showed a dynamic steady state depolarization of
      multiple nodes, strongly suggesting a depolarization mechanism for HFAC
      conduction block.

PMID- 17200887
TI  - Spectrum of cyanide toxicity and allocation in Heliconius erato and Passiflora
      host plants.
AB  - The larvae of three races of Heliconius erato were fed various species of
      Passiflora containing varying levels of cyanoglucosides. The mortality rate of
      larvae and pupae rose when larvae were fed species of Passiflora capable of
      releasing larger quantities of cyanide. When larvae were fed species of
      Passiflora with these properties, the resulting adult butterflies also released
      higher levels of cyanide. This may serve as a defense mechanism. The compounds
      responsible for the release of cyanide were not evenly distributed throughout the
      adult butterfly's body. The thorax contained the highest concentration of
      cyanogenic substances, followed by the head, wings, and abdomen. The younger
      tissues of Passiflora plants had higher levels of cyanide-releasing compounds
      than stems and mature leaves. Cyanogenic glycoside distribution within the plants
      is consistent with optimal allocation theory. The levels of cyanide-releasing
      substances in plants varied depending on the season.

PMID- 17200889
TI  - Role of (3Z,6Z,8E)-dodecatrien-1-ol in trail following, feeding, and mating
      behavior of Reticulitermes hesperus.
AB  - Trail pheromones mediate communication among western subterranean termites,
      Reticulitermes hesperus Banks. Repetitive passages of >or=28 termites were
      required to establish a pheromone trail and trails needed to be reinforced
      because they lasted <48 hr. The minimal threshold concentration for inducing
      responses from termite workers and secondary reproductives was between 0.01 and
      0.1 fg/cm of (3Z,6Z,8E)-dodecatrien-1-ol (henceforth, dodecatrienol). Workers
      showed optimal trail-following behavior to dodecatrienol at a concentration of 10
      fg/cm. Trails with concentrations >10 pg/cm were repellent to workers. Workers
      did not detect pheromone gradients, responding equally to increasing or
      decreasing gradients of dodecatrienol, and termite workers were not able to
      differentiate between different concentrations of dodecatrienol. Termites
      preferred dodecatrienol trails to 2-phenoxyethanol trails. Antennae played a key
      role in trail pheromone perception. Dodecatrienol acted as an arrestant for
      worker termites (10 fg/cm2) and male alates (5 ng/cm2), whereas sternal gland
      extracts from females attracted male alates. Workers and alates, upon contact
      with filter paper disks treated with higher doses (10 fg/cm2 and 5 ng/cm2,
      respectively) of dodecatrienol, were highly excited (increased antennation and
      palpation) and repeatedly returned to the treated disks. Dodecatrienol did not
      act as a phagostimulant when offered on a paper towel disk. Reticulitermes
      hesperus is highly responsive to dodecatrienol, and it may play an important role
      in orientation of workers and alates.

PMID- 17200888
TI  - Differential attraction of Heliothis subflexa males to synthetic pheromone lures
      in Eastern US and Western Mexico.
AB  - The mate attraction signal of Heliothis subflexa (Hs) females consists of a
      multicomponent sex pheromone blend. In this study, we assessed the intraspecific
      importance of three groups of compounds found in Hs pheromone glands: three
      acetate esters (Z7-16:OAc, Z9-16:OAc, and Z11-16:OAc), two 14-carbon aldehydes
      (14:Ald and Z9-14:Ald), and one 16-carbon alcohol (Z11-16:OH). Because the
      relative importance of pheromone components may vary in different regions, we
      conducted experiments in Eastern US (North Carolina) and Western Mexico
      (Jalisco). Our experiments in Eastern US showed that when the acetates were
      omitted from a 7-component blend in rubber septa, fewer males were caught in cone
      traps. Subsequent experiments conducted both in Eastern US and Western Mexico
      indicated that the addition of Z9-16:OAc alone does not increase attraction of
      male Hs, while Z11-16:OAc does. The Hs male response to Z7-16:OAc differed
      between the two regions. In Eastern US, significantly more males were attracted
      to a minimal three-component blend to which Z7-16:OAc was added, but this was not
      the case in Western Mexico. The two 14-carbon aldehydes also showed differential
      attraction between the two regions. 14:Ald and Z9-14:Ald appeared not to play any
      role in the sexual communication of Hs in Eastern US, but reduced trap catches in
      Western Mexico. The alcohol Z11-16:OH was tested in two concurrent dose-response
      studies with Hs males in Western Mexico, one using a minimal blend and one using
      a complete blend. The minimal three-component blend provided a more
      discriminating tool for delineating dose-response effects of Z11-16:OH than the
      seven-component blend. In the minimal blend, the optimal dose of Z11-16:OH was
      1%, while in the complete blend similar numbers of males were caught when the
      alcohol ranged from 1 to 25%.

PMID- 17200890
TI  - Zea mays: benzoxazolinone detoxification under sulfur deficiency conditions--a
      complex allelopathic alliance including endophytic Fusarium verticillioides.
AB  - Benzoxazolinone detoxification is similar in plants grown under sulfur deficiency
      conditions and in control plants grown with an optimal S supply. However, when S
      deficient plants were treated with metolachlor before benzoxazolin-2(3H)-one
      (BOA) incubation, detoxification was reduced, as indicated by a lower
      accumulation of the detoxification products BOA-6-O-glucoside and glucoside
      carbamate and by a loss of BOA-6-OH glucosyltransfease activity. Root colonizing
      microorganisms and the endophytic fungus Fusarium verticillioides participated in
      benzoxazolinone detoxification by converting the compound to 2-acetamidophenol
      (AAP) or O-hydroxyphenyl malonamic acid (OHPMA), a process accompanied by the
      appearance of phenoxazinone. Maize roots, however, absorbed AAP and OHPMA only in
      traces. Absorbed traces of OHPMA stimulated maize radicle growth, and traces of
      AAP stimulated cress. Phenoxazinone inhibited the growth of cress radicles at
      concentrations higher than 500 microM, whereas maize radicles were hardly
      affected. F. verticillioides did not convert benzoxazolinone to any known
      microbial degradation product when the medium of maize seedlings was inoculated
      with the fungus under sterile condition. Plant-fungus interactions seem to be
      important in plant survival of allelopathic attacks. This study points to a
      complicated network of allelopathic interactions that are influenced by biotic
      and abiotic factors, including herbicides.

PMID- 17200891
TI  - The male abdominal glands of Leucophaea maderae: chemical identification of the
      volatile secretion and sex pheromone function.
AB  - In Leucophaea maderae, male calling behavior involves the release of a sex
      pheromone from the abdominal sternal glands. An extract of sternal glands
      attracted conspecific females over a distance. The compounds present were
      identified as hydroxy-3-butan-2-one, (2R, 3R)-butanediol, senecioic acid, and (E)
      2-octenoic acid. The same components are also present in male tergal glands. The
      identified compounds were tested on their own and in mixtures. Their biological
      function is discussed.

PMID- 17200893
TI  - Percutaneous retrieval of a retained appendicolith.

PMID- 17200892
TI  - Thyroid hormone and the growth plate.
AB  - Thyroid hormone was first identified as a potent regulator of skeletal maturation
      at the growth plate more than forty years ago. Since that time, many in vitro and
      in vivo studies have confirmed that thyroid hormone regulates the critical
      transition between cell proliferation and terminal differentiation in the growth
      plate, specifically the maturation of growth plate chondrocytes into hypertrophic
      cells. However these studies have neither identified the molecular mechanisms
      involved in the regulation of skeletal maturation by thyroid hormone, nor
      demonstrated how the systemic actions of thyroid hormone interface with the local
      regulatory milieu of the growth plate. This article will review our current
      understanding of the role of thyroid hormone in regulating the process of
      endochondral ossification at the growth plate, as well as what is currently known
      about the molecular mechanisms involved in this regulation.

PMID- 17200894
TI  - Sac hygroma after endovascular abdominal aortic aneurysm repair: successful
      treatment with endograft relining.
AB  - Aneurysm sac expansion following endovascular abdominal aortic aneurysm repair
      (EVAR) is typically associated with endoleaks that can be readily diagnosed on
      computed tomographic angiography (CTA), ultrasound, or catheter-directed
      arteriography. Sac hygromas are a cause of sac expansion without apparent
      endoleak and are presumed to be a result of ultrafiltration of serum manifested
      by accumulation of fibrinous, gelatinous material within the aneurysm sac
      following EVAR. Although there are no reported associated ruptures, sac expansion
      is nevertheless disconcerting and intervention is presumably indicated. We report
      a case of an expanding aneurysm after EVAR secondary to sac hygroma that was
      successfully treated with relining of the existing, original endograft.

PMID- 17200895
TI  - Percutaneous transhepatic use of a cutting balloon in the treatment of a benign
      common bile duct stricture.

PMID- 17200896
TI  - Prospective nonrandomized trial of manual compression and Angio-Seal and
      Starclose arterial closure devices in common femoral punctures.
AB  - We compared the use of manual compression and Angio-Seal and Starclose arterial
      closure devices to achieve hemostasis following common femoral artery (CFA)
      punctures in order to evaluate safety and efficacy. A prospective nonrandomized,
      single-center study was carried out on all patients undergoing CFA punctures over
      1 year. Hemostasis was achieved using manual compression in 108 cases, Angio-Seal
      in 167 cases, and Starclose in 151 cases. Device-failure rates were low and not
      significantly different in the two groups (manual compression and closure
      devices; p = 0.8). There were significantly more Starclose (11.9%) patients
      compared to Angio-Seal (2.4%), with successful initial deployment subsequently
      requiring additional manual compression to achieve hemostasis (p < 0.0001). A
      significant number of very thin patients failed to achieve hemostasis (p =
      0.014). Major complications were seen in 2.9% of Angio-Seal, 1.9% of Starclose,
      and 3.7% of manual compression patients, with no significant difference
      demonstrated; 4.7% of the major complications were seen in female patients
      compared to 1.3% in males (p = 0.0415). All three methods showed comparable
      safety and efficacy. Very thin patients are more likely to have failed hemostasis
      with the Starclose device, although this did not translate into an increased
      complication rate. There is a significant increased risk of major puncture-site
      complications in women with peripheral vascular disease.

PMID- 17200897
TI  - Fibromuscular dysplasia-related renal artery stenosis associated with aneurysm:
      successive endovascular therapy.
AB  - Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular
      disease. FMD of the renal arteries is one of the leading causes of curable
      hypertension. The simultaneous occurrence of FMD and renal artery aneurysm has
      been described previously. In this case, we present a fibrodysplastic lesion and
      an aneurysm in a renal artery treated with a percutaneous transluminal
      angioplasty and coil embolization.

PMID- 17200898
TI  - Radiological interventions for correction of central venous port catheter
      migrations.
AB  - The purpose of the study is to evaluate radiological-interventional central
      venous port catheter corrections in migrated/malpositioned catheter tips. Thirty
      patients with migrated/malpositioned port catheter tips were included in this
      retrospective analysis. To visualize the catheter patency, a contrast-enhanced
      port catheter series was performed, followed by transfemoral port catheter
      correction with various 5F angiographic catheters (pigtail, Sos Omni), goose-neck
      snare, or combinations thereof. One patient showed spontaneous reposition of the
      catheter tip. In 27 of 29 patients (93%), radiological-interventional port
      catheter correction was successful. In two patients, port catheter malposition
      correction was not possible because of the inability to catch either the catheter
      tip or the catheter in its course, possibly due to fibrin sheath formation with
      attachment of the catheter to the vessel wall. No disconnection or port catheter
      dysfunction was observed after correction. In migrated catheter tips,
      radiological-interventional port catheter correction is a minimally invasive
      alternative to port extraction and reimplantation. In patients with a fibrin
      sheath and/or thrombosis, port catheter correction is often more challenging.

PMID- 17200899
TI  - Use of the 4F Rosch inferior mesenteric catheter in embolization procedures in
      the pelvis: a review of 300 cases.
AB  - The aim of this study is to evaluate the use of a 4F Rosch inferior mesenteric
      (RIM) catheter for pelvic embolization procedures. Between October 2000 and
      January 2006, 364 patients (357 female, 7 male; age: 23-67 years) underwent
      embolization of various pathologies [uterine fibroids (n = 324), pure adenomyosis
      of the uterus (n = 19), postpartum hemorrhage (n =1), traumatic or postoperative
      hemorrhage (n = 9), bleeding related to cervical cancer (n =7), AV malformation
      of the uterus (n = 2) and high-flow priapism (n = 2)] at a single institution. In
      all cases, bilateral catheterization was primarily attempted with the use of a 4F
      hook-shaped braided endhole catheter (Rosch-Inferior-Mesenteric, RIM-Catheter,
      Cordis, Miami, FL). Frequency of initial failure to catheterize the vascular
      territory of interest and carry out the embolization were recorded and the types
      of difficulty encountered were noted. Catheterization of the main stem of the
      vessel territory of interest with the use of a unilateral femoral approach and
      the 4F RIM catheter was successful in 334/364 (91.8%) the embolization cases.
      Bilateral catheterization of the internal iliac arteries using a single common
      femoral artery access and the 4F RIM catheter was achieved in 322/364 (88.5%)
      patients. In 12/364 (3.3%) patients, a contralateral puncture was performed and
      the same 4F catheter was used. In 28/364 (7.7%) cases the 4F RIM catheter was
      exchanged for a catheter with a cobra-shaped or sidewinder configuration. The 4F
      RIM catheter is a simple and valuable alternative to catheters and techniques
      commonly employed for pelvic artery embolization.

PMID- 17200900
TI  - Pain relief following percutaneous vertebroplasty: results of a series of 283
      consecutive patients treated in a single institution.
AB  - The aim of this study was to assess if percutaneous vertebroplasty (PVP) could
      relieve back pain, reduce drug consumption, and improve the mobility of patients
      with metastases and vertebral compression fractures. From August 2002 to July
      2004, 283 patients (216 females; mean age: 73.8 +/- 9.9 years) underwent PVP on
      749 vertebrae. Pain was evaluated with the pain intensity numeric rating scale
      (PI-NRS) (0 = no pain; 10 = worst pain) before the procedure and at the end point
      in September 2004 (follow-up:1-24 months; median: 7 months). A reduction of at
      least two points of the PI-NRS score was considered clinically relevant. Two
      hundred four patients were available for evaluation at the end point. Overall
      results showed a reduction of the median pain score from 8 at baseline to 1 at
      the end point (p < 0.0001); a clinically relevant pain reduction was observed in
      176/205 patients (86%); 89/147 patients (61%) gave up a brace support (p <
      0.0001); and 117/190 patients (62%) gave up drug therapy. Results were similar in
      different subgroups stratified according to age, underlying pathology, number of
      fractured or treated vertebrae, and length of follow-up. This study adds evidence
      that PVP is effective in treating painful vertebral fractures. A significant
      reduction in drug assumption and significant mobility improvement can also be
      achieved.

PMID- 17200901
TI  - Feasibility of angioplasty and stenting for abdominal aortic lesions adjacent to
      previously stented visceral artery lesions in patients with Takayasu arteritis.
AB  - Two young female patients with Takayasu arteritis presented with symptomatic long
      segment abdominal aortic stenosis in the vicinity of previously deployed celiac
      and renal artery stents that projected markedly into the narrowed aortic lumen.
      Crushing or distortion of the visceral artery stents during aortic angioplasty
      was avoided by performing simultaneous or alternating balloon dilatations in the
      aorta and in the visceral artery stents. Consequently, the visceral artery stents
      remained patent and shortened longitudinally, allowing unhindered deployment of
      Wallstents in the adjacent aorta and abolition of a pressure gradient across the
      aortic lesions. Access to side branches covered by the Wallstent was obtained
      without difficulty, enabling the performance of balloon dilatation in multiple
      side branches and ostial stent deployment in a renal artery. These techniques
      could increase the scope of endovascular therapy in the treatment of patients
      with Takayasu arteritis.

PMID- 17200902
TI  - Long-term outcome of a hepatocellular carcinoma 7(1/2) years after surgery and
      repeated radiofrequency ablation: case report and review of the literature.
AB  - An interesting case is presented of a 78-year-old patient with cirrhosis who was
      managed with combined treatment (surgery and radiofrequency (RF) ablation) for
      hepatocellular carcinoma (HCC) and has survived for 7(1/2) years. Elevation of
      the alpha-FP (alpha-fetoprotein) levels was noted 2 years after surgery. CT
      demonstrated two lesions: one central at the remaining right liver lobe, and the
      other at the excision site. Biopsy of the lesions confirmed the diagnosis of HCC
      for both of them. RF ablation of these two lesions was performed in one session
      with technical success. Four and a half years after the first RF ablation a new
      recurrence was demonstrated at the CT follow-up control. RF ablation was again
      applied successfully. The imaging findings and the therapeutic percutaneous
      management of this patient along with the natural course of HCC and its
      recurrence are discussed, and the literature concerning risk factors is reviewed.

PMID- 17200903
TI  - Distal embolization after stenting of the vertebral artery: diffusion-weighted
      magnetic resonance imaging findings.
AB  - PURPOSE: We retrospectively evaluated our experience with stenting of the
      vertebral artery in an effort to determine the risk of distal embolization
      associated with the procedure. METHODS: Between June 2000 and May 2005, 35
      patients with 38 stenting procedures for atherosclerotic disease of the vertebral
      origin in our institution were identified. The average age of the patients was
      60.3 years (range 32-76 years). Sixteen of these patients (with 18 stents) had MR
      imaging of the brain with diffusion-weighted imaging and an apparent diffusion
      coefficient map within 2 days before and after procedure. RESULTS: On seven of
      the 16 postprocedural diffusion-weighted MR images, a total of 57 new
      hyperintensities were visible. All these lesions were focal in nature. One
      patient demonstrated a new diffusion-weighted imaging abnormality in the anterior
      circulation without MR evidence of posterior circulation ischemia. Six of 16
      patients had a total of 25 new lesions in the vertebrobasilar circulation in
      postprocedural diffusion-weighted MR images. One patient in this group was
      excluded from the final analysis because the procedure was complicated by basilar
      rupture during tandem stent deployment in the basilar artery. Hence, new
      diffusion-weighted imaging abnormalities were noted in the vertebrobasilar
      territory in 5 of 15 patients after 17 stenting procedures, giving a 29% rate of
      diffusion-weighted imaging abnormalities per procedure. No patient with bilateral
      stenting had new diffusion-weighted imaging abnormalities. CONCLUSION: Stenting
      of stenoses of the vertebral artery origin may be associated with a significant
      risk of asymptomatic distal embolization. Angiography, placement of the guiding
      catheter, inflation of the stent balloon, and crossing the lesion with guidewires
      or balloon catheters may potentially cause distal embolization. Further studies
      to evaluate measures to increase the safety of vertebral artery stenting, such as
      the use of distal protection devices or short-term postprocedural
      anticoagulation, should be considered for patients with clear indications for
      this procedure.

PMID- 17200904
TI  - Clinicopathologic features and results of transcatheter arterial
      chemoembolization for osteosarcoma.
AB  - PURPOSE: To evaluate the effect of transcatheter arterial chemoembolization
      (TACE) for osteosarcoma and to describe the clinicopathologic features produced
      by TACE as well as the effect of different embolic materials. METHODS: From
      January 1998 to December 2003, preoperative TACE was carried out in 32 patients.
      The preoperative and postoperative clinical response, levels of alkaline
      phosphatase (AKP), leukocyte count, and clinicopathologic features were recorded.
      We also compared the effect of different embolic materials: adriblastine gelatin
      microspheres, anhydrous alcohol, common bletilla tuber, and gelatin sponge
      particles. RESULTS: The levels of AKP were significantly decreased after
      treatment (p < 0.05), but there was no significant difference in the leukocyte
      count. Large areas of necrosis were found histologically within 85.5% tumors
      after TACE. Embolic agents such as adriblastine microspheres, anhydrous alcohol,
      and common bletilla tuber have better clinical effects than gelatin sponge
      particles, but there was no significant difference among the first three embolic
      materials. After treatment, no serious complications were noted. During
      successful follow-up for 86 months, the survival rate after TACE at 1, 2, and 5
      years was 95.5%, 72%, and 42% respectively. CONCLUSION: TACE accelerated tumor
      necrosis and shrank the tumor volume, thus making adequate tumor resection
      possible. The optimal time to operate is 10-14 days after TACE. TACE in
      combination with limb salvage surgery and postoperative periodical chemotherapy
      may be beneficial for increasing local control rates.

PMID- 17200905
TI  - Percutaneous ethanol injection of unresectable medium-to-large-sized hepatomas
      using a multipronged needle: efficacy and safety.
AB  - Fine needles with an end hole or multiple side holes have traditionally been used
      for percutaneous ethanol injection (PEI) of hepatomas. This study retrospectively
      evaluates the safety and efficacy of PEI of unresectable medium-to-large (3.5-9
      cm) hepatomas using a multipronged needle and with conscious sedation. Twelve
      patients, eight men and four women (age 51-77 years; mean: 69) received PEI for
      hepatomas, mostly subcapsular or exophytic in location with average tumor size of
      5.6 cm (range: 3.5-9.0 cm). Patients were consciously sedated and an 18G
      retractable multipronged needle (Quadrafuse needle; Rex Medical, Philadelphia,
      PA) was used for injection under real-time ultrasound guidance. By varying the
      length of the prongs and rotating the needle, the alcohol was widely distributed
      within the tumor. The progress of ablation was monitored by contrast-enhanced
      ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) after
      each weekly injection and within a month after the final (third) injection and 3
      months thereafter. An average total of 63 mL (range: 20-154 ml) of alcohol was
      injected per patient in an average of 2.3 sessions. Contrast-enhanced CT,
      ultrasound, or MRI was used to determine the degree of necrosis. Complete
      necrosis was noted in eight patients (67%), near-complete necrosis (90-99%) in
      two (16.7%), and partial success (50-89%) in two (16.7%). Follow-up in the first
      9 months showed local recurrence in two patients and new lesions in another.
      There was no mortality. One patient developed renal failure, liver failure, and
      localized perforation of the stomach. He responded to medical treatment and
      surgery was not required for the perforation. One patient had severe
      postprocedural abdominal pain and fever, and another had transient
      hyperbilirubinemia; both recovered with conservative treatment. PEI with a
      multipronged needle is a new, safe, and efficacious method in treating medium-to
      large-sized hepatocellular carcinoma under conscious sedation. Its survival
      benefits require further investigations.

PMID- 17200906
TI  - The epistemology of evidence-based medicine.

PMID- 17200907
TI  - Laparoscopy for every acute appendicitis? The authors reply.

PMID- 17200909
TI  - The effect of escalating feedback on the acquisition of psychomotor skills for
      laparoscopy.
AB  - BACKGROUND: In the acquisition of new skills that are difficult to master, such
      as those required for laparoscopy, feedback is a crucial component of the
      learning experience. Optimally, feedback should accurately reflect the task
      performance to be improved and be proximal to the training experience. In
      surgery, however, feedback typically is in vivo. The development of virtual
      reality training systems currently offers new training options. This study
      investigated the effect of feedback type and quality on laparoscopic skills
      acquisition. METHODS: For this study, 32 laparoscopic novices were prospectively
      randomized into four training conditions, with 8 in each group. Group 1 (control)
      had no feedback. Group 2 (buzzer) had audio feedback when the edges were touched.
      Group 3 (voiced error) had an examiner voicing the word "error" each time the
      walls were touched. Group 4 (both) received both the audio buzzer and "error"
      voiced by the examiner All the subjects performed a maze-tracking task with a
      laparoscopic stylus inserted through a 5-mm port to simulate the fulcrum effect
      in minimally invasive surgery (MIS). A computer connected to the stylus scored an
      error each time the edge of the maze was touched, and the subjects were made
      aware of the error in the aforementioned manner. Ten 2-min trials were performed
      by the subjects while viewing a monitor. At the conclusion of training, all the
      subjects completed a 2-min trial of a simple laparoscopic cutting task, with the
      number of correct and incorrect incisions recorded. RESULTS: Group 4 (both) made
      significantly more correct incisions than the other three groups (F = 12.13; df =
      3, 28; p < 0.001), and also made significantly fewer errors or incorrect
      incisions (F = 14.4; p < 0.0001). Group 4 also made three times more correct
      incisions and 7.4 times fewer incorrect incisions than group 1 (control).
      CONCLUSIONS: The type and quality of feedback during psychomotor skill
      acquisition for MIS have a large effect on the strength of skills generalization
      to a simple MIS task and should be given serious consideration in curriculum
      design for surgical training using simulation tasks.

PMID- 17200908
TI  - The current role of laparoscopic surgery for gastroesophageal reflux disease in
      infants and children.
AB  - BACKGROUND: The benefits of surgery for gastroesophageal reflux disease (GERD) in
      infants and children have been questioned in the recent literature. The goal of
      this review was to determine the best current practice for the diagnosis and
      management of this disease. METHODS: The literature was reviewed for all recent
      English language publications on the management of GERD in 8- to 10-year-old
      patients. RESULTS: In infants and children, GERD has multiple etiologies, and an
      understanding of these is important for determining which patients are the best
      surgical candidates. Proton pump inhibitors (PPIs) have become the mainstay of
      current treatment for primary GERD. Although laparoscopic surgery appears to be
      better than open surgery, there remains some morbidity and complications that
      careful patient selection can minimize. CONCLUSION: Surgery for GERD should be
      performed only after failure of medical management or for specific problems that
      mandate it.

PMID- 17200910
TI  - Gastric emptying of glucose solution and associated plasma concentrations of GLP
      1, GIP, and PYY before and after fundoplication.
AB  - BACKGROUND: This study was designed to assess the relationship between gastric
      emptying of glucose solution and the ensuing plasma concentrations of glucagon
      like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic
      polypeptide (GIP) in patients having undergone fundoplication for
      gastroesophageal reflux (GERD). SUBJECTS AND METHODS: In 10 male patients the
      emptying of 50% glucose solution was determined scintigraphically and its
      relationship with plasma glucose, GLP-1, PYY, and GIP concentrations was studied
      before and 3 months after fundoplication. RESULTS: In the first 30 min after
      glucose ingestion, emptying was significantly (p = 0.048) faster after
      fundoplication than before. Emptying and GLP-1 and GIP correlated: the faster the
      emptying during the first 30 min the greater the concentrations integrated over
      that period (p = 0.04; p = 0.01; p = 0.02). Emptying and PYY concentrations were
      unrelated. In the 120-180 min. period, blood glucose concentrations were lower
      the faster the emptying in the initial 30 min (p = 0.06) and the entire 50-min
      recording period (p = 0.03) had been. The GLP-1 concentrations integrated over
      the first 30 min correlated inversely with the integrated plasma glucose during
      the third hour after ingestion (p = 0.004). CONCLUSIONS: After fundoplication,
      gastric emptying may, if accelerated in its initial phases, give rise to greater
      and earlier increases in plasma glucose, GLP-1, and GIP concentrations and thus
      to reactive hypoglycemia.

PMID- 17200912
TI  - Detection of carcinoembryonic antigen messenger RNA-expressing cells in
      peripheral blood 7 days after curative surgery is a novel prognostic factor in
      colorectal cancer.
AB  - BACKGROUND: The significance of detection of circulating cancer cells in blood
      during surgery in patients with colorectal cancer (CRC) remains controversial.
      Experimental study revealed that the cancer cells injected from the vein
      disappeared completely until 7 days. The aim of this study was to clarify that
      the detection of circulating cancer cells in blood taken later than 7 days after
      curative surgery may be a prognostic factor. METHODS: Two hundred consecutive
      patients with CRC who underwent potentially curative surgery were the subjects.
      Peripheral blood was collected between 7 and 10 days after resection. Cancer
      cells were detected using reverse transcriptase-polymerase chain reaction
      targeting carcinoembryonic antigen (CEA) messenger RNA (mRNA). The median follow
      up period was 52 months (range: 34-69 months). RESULTS: The overall positive
      incidence of CEA mRNA was 22%. Detection of CEA mRNA was not significantly
      related to conventional clinicopathological findings. Recurrence has been
      confirmed in 55 patients (28%). The recurrence rate was significantly higher in
      patients with rectal cancer, deep penetration, lymph node metastasis,
      preoperative chemoradiotherapy and positive CEA mRNA. The CEA mRNA positive
      patients showed significantly poorer disease free survival (DFS) and overall
      survival (OS) than the negative patients (DFS, P = 0.007; OS, P = 0.04).
      Multivariate analysis revealed that the positive expression of CEA mRNA (P <
      0.01) as well as the tumor location and TNM stage classification was identified
      as the significant risk factors for recurrence. CONCLUSIONS: Detection of CEA
      mRNA expressing cells in peripheral blood 7 days after curative surgery is a
      novel independent factor predicting recurrence in patients with CRC.

PMID- 17200911
TI  - Tonotopic distribution of short-term adaptation properties in the cochlear nerve
      of normal and acoustically overexposed chicks.
AB  - Cochlear nerve adaptation is thought to result, at least partially, from the
      depletion of neurotransmitter stores in hair cells. Recently, neurotransmitter
      vesicle pools have been identified in chick tall hair cells that might play a
      role in adaptation. In order to understand better the relationship between
      adaptation and neurotransmitter release dynamics, short-term adaptation was
      characterized by using peristimulus time histograms of single-unit activity in
      the chick cochlear nerve. The adaptation function resulting from 100-ms pure tone
      stimuli presented at the characteristic frequency, +20 dB relative to threshold,
      was well described as a single exponential decay process with an average time
      constant of 18.6+/-0.8 ms (mean+/-SEM). The number of spikes contributed by the
      adapting part of the response increased tonotopically for characteristic
      frequencies up to approximately 0.8 kHz. Comparison of the adaptation data with
      known physiological and anatomical hair cell properties suggests that depletion
      of the readily releasable pool is the basis of short-term adaptation in the
      chick. With this idea in mind, short-term adaptation was used as a proxy for
      assessing tall hair cell synaptic function following intense acoustic
      stimulation. After 48 h of exposure to an intense pure tone, the time constant of
      short-term adaptation was unaltered, whereas the number of spikes in the adapting
      component was increased at characteristic frequencies at and above the exposure
      frequency. These data suggest that the rate of readily releasable pool emptying
      is unaltered, but the neurotransmitter content of the pool is increased, by
      exposure to intense sound. The results imply that an increase in readily
      releasable pool size might be a compensatory mechanism ensuring the strength of
      the hair cell afferent synapse in the face of ongoing acoustic stress.

PMID- 17200914
TI  - [40 years beta-adrenoceptor blockers in psychiatry].
AB  - Beta-adrenoceptor blockers belong to the most successful drug classes of
      medicine. Mainly they are used in internal medicine. 40 years ago beta
      adrenoceptor blockers have occasionally been used in psychiatry for the treatment
      of anxiety disorders. Over the past four decades, the effects of beta
      adrenoceptor blockers in the treatment of schizophrenic and manic psychoses,
      withdrawal syndromes and aggressive behaviour with temper outbursts has been
      investigated. Beta-adrenoceptor blockers are also used in the treatment of side
      effects of psychopharmacological agents like neuroleptic or antidepressant
      induced tachycardias, lithium-induced tremor, antipsychotic-induced akathisia or
      tardive dyskinesia as well. Since the mid-nineties it has been attempted to
      improve the efficacy of antidepressant agents by means of the 5-HT-(1a)
      receptorantagonist pindolol. Presumedly memory consolidation of traumatic events
      can be enhanced by adrenergic activation. Therefore some open clinical trials
      investigated the effects of propranolol, a lipid soluble drug, which crosses the
      blood-brain barrier easily, to reduce the manifestation of PTSD. The present
      review presents the results of the literature with respect to the indications for
      beta-blockers in psychiatry. Considering evidence-based-medicine criteria beta
      blockers are indicated to treat lithium-induced tremor, antipsychotic-induced
      akathisia and to reduce aggressive behavior of patients with brain-injuries.

PMID- 17200913
TI  - Timing of resection of liver metastases synchronous to colorectal tumor: proposal
      of prognosis-based decisional model.
AB  - BACKGROUND: Timing of hepatectomy for synchronous metastases of colorectal cancer
      is still debated. The aim of this retrospective study was to analyze prognostic
      factors after synchronous and delayed liver resections to define selection
      criteria for choosing timing of hepatectomy. METHODS: The study was performed on
      127 patients with synchronous metastases undergoing radical hepatectomy. We
      divided patients according to the timing of hepatectomy: 70 synchronous (group A)
      and 57 delayed (group B). RESULTS: Overall survival was similar between the two
      groups (5-year survival 30.8% vs. 32.0% A vs. B, P = .406). The multivariate
      analysis evidenced four independent prognostic factors in group A: male sex (P =
      .04), T4 (P = .0035), more than three metastases (P = .0001), and metastatic
      infiltration of nearby structures (P < .0001). There were no statistically
      significant prognostic factors in group B. Patients with more than three
      metastases had a significantly worse survival in group A than in group B (3-year
      survival, 15.0% vs. 34.3%, P = .007); similarly, borderline significant
      difference was encountered in patients with T4 primary tumor (3-year survival,
      16.7% vs. 60%, P = .064) CONCLUSIONS: Patients with liver metastases synchronous
      with colorectal cancer with T4 primary tumor, metastasis infiltration of
      neighboring structures, and especially with more than three metastases should
      receive neoadjuvant chemotherapy before liver resection.

PMID- 17200915
TI  - [Oxcarbazepine in the treatment of epilepsy].
AB  - BACKGROUND: Oxcarbazepine (OXC; Timox) is a new antiepileptic drug (AED)
      chemically related to carbamazepine (CBZ), with comparable efficacy but superior
      safety according to controlled clinical trials. In a prospective, post-marketing
      surveillance (PMS) study the efficacy and tolerability of OXC were investigated
      under conditions of daily routine practice. METHODS: The treatment of 1385 male
      and female epilepsy patients aged between 1 month and 94 years, who were newly
      stabilized on OXC or changed over from another AED, was documented in 362 centers
      over a period of 8 weeks. Efficacy and tolerability were assessed by documenting
      the frequency of seizures and adverse drug reactions (ADRs) and by global
      efficacy and tolerability ratings obtained from the patients and investigators.
      RESULTS: Before the PMS study, 688/1335 patients (49.7 %) had received pre
      treatment with CBZ, 342 (24.7 %) had received another AED and 335 (25.6 %) had
      had no AED pre-treatment (initial OXC monotherapy). In 161 patients pre-treated
      with CBZ (23,4 % of 688) an immediate (overnight) switch to OXC was performed
      while most others were switched during a titration phase. Of the patients with
      CBZ pre-treatment 21 % were switched to OXC at the recommended dose ratio of 1 :
      1.4 - 1 : 1.6 (CBZ : OXC) while roughly 60 % were changed to OXC with a lower
      ratio. In the total sample the median OXC maintenance dose was 900 mg/day. During
      treatment with OXC the frequency of seizures per 4 weeks decreased by an average
      of 76 % in comparison to a retrospective pre-phase. 74 % of the patients showed
      an improved seizure situation, and 40.5 % became seizure-free under OXC (patients
      with initial monotherapy became seizure-free in 62 % of the cases). 71 % of the
      patients showed a reduction of their seizure frequency versus baseline by > or =
      50 %. ADRs were reported in 10,8 % of the participants (incidence: 1 in 459 days
      of exposition to OXC; overnight switching from CBZ to OXC: 1 event in 1284 days).
      Only 2.5 % of the patients terminated OXC administration due to ADRs while 92 %
      continued treatment with OXC beyond the end of the study. CONCLUSIONS: The
      results underline the high antiepileptic efficacy and good tolerability of OXC
      previously demonstrated in controlled clinical trials. When changing from CBZ to
      OXC, immediate (overnight) switching showed particularly favorable results.

PMID- 17200916
TI  - Bromoallenes as allyl dication equivalents in the presence or absence of
      palladium(0): direct construction of bicyclic sulfamides containing five- to
      eight-membered rings by tandem cyclization of bromoallenes.
AB  - A highly regioselective synthesis of bicyclic sulfamides is described. Based on
      our recent discovery that bromoallenes can act as allyl dication equivalents in
      the presence of a palladium catalyst and alcohol, we investigated tandem
      cyclization of bromoallenes bearing a sulfamide group. It is found that some
      bromoallenes act as allyl dication equivalents even in the absence of a
      palladium(0) catalyst to afford cyclosulfamides containing five- or six-membered
      rings. While the palladium-free cyclization is dependent on the substrate
      structure affording the bicyclic sulfamides through the first cyclization onto
      the proximal or central carbon atom of the bromoallenes, the palladium-catalyzed
      reaction strongly promotes the first cyclization onto the central allenic carbon
      atom to afford bicyclic sulfamides containing a seven- or eight-membered ring.
      Formation of two types of bicyclic sulfamides from single bromoallenes by simply
      changing the reaction conditions is also described.

PMID- 17200917
TI  - Self-assembly of halogenated cobaltacarborane compounds: boron-assisted C--H...X-
      B hydrogen bonds?
AB  - Full structural characterisation and complete synthetic procedures for three
      monohalogenated cobaltacarborane compounds closo-[3-Co(eta5-C5H5)-8-X-1,2
      C2B9H10] (X=Cl (1), Br (2), I (3)) and the dibromo derivative closo-[3-Co(eta5
      C5H5)-8,9-Br2-1,2-C2B9H9] (4) are reported. The supramolecular structures of 1,
      3, and 4 reveal the existence of intermolecular C--HX--B interactions. The role
      of these interactions has been investigated through a CSD search and subsequent
      analysis of the reported crystalline compounds. The results show that halogens
      become reasonably good hydrogen-bond acceptors when bonded to boron and, in this
      respect, are comparable in strength to metal-bound halogens.

PMID- 17200918
TI  - Shape-controlled synthesis and self-assembly of hexagonal covellite (CuS)
      nanoplatelets.
AB  - Single-crystalline, hexagonal covellite (CuS) nanoplatelets were successfully
      synthesized through a facile, inexpensive, reproducible, and improved
      solvothermal process in toluene at 120 degrees C for 24 h with hexadecylamine as
      a capping agent and copper acetate and carbon disulfide as precursors. These
      nanoplatelets are about 26+/-1.5 nm in diameter and 8+/-1.2 nm thick, and have a
      tendency to self-assemble into pillarlike nanostructures with face-to-face
      stacks, raftlike nanostructures with side-by-side arrays, and stratiform
      nanostructures with layer-by-layer self-assembly. The crystal shape, morphology,
      and crystallographic orientation of the covellite obtained were investigated by
      means of XRD, TEM, and high-resolution TEM, and a potential self-assembly
      mechanism was proposed.

PMID- 17200919
TI  - Microporous organic materials from hydrophobic dipeptides.
AB  - In the last few years dipeptides with two hydrophobic residues (hydrophobic
      dipeptides) have emerged as an unexpected source of stable microporous organic
      materials. Supramolecular self-assembly of the rather small building blocks is
      dictated by stringent demands on the hydrogen-bond formation by the peptide main
      chains and the aggregation of hydrophobic entities in the side chains. A
      systematic survey of structures derived from single-crystal X-ray diffraction
      studies has revealed the existence of two large classes of structures, differing
      in the dimensionality of the hydrogen-bonding patterns in the crystals and the
      nature of the channels. The present review summarizes the structural properties
      of the microporous dipeptides and discusses their potential applications.

PMID- 17200920
TI  - Synthesis by radical cyclization and cytotoxicity of highly potent bioreductive
      alicyclic ring fused [1,2-a]benzimidazolequinones.
AB  - The key step in the synthesis of new five, six and seven-membered alicyclic ring
      [1,2-a]-fused bioreductive benzimidazolequinones was radical cyclisation. Six and
      seven-membered tributyltin hydride-mediated homolytic aromatic substitutions of
      nucleophilic N-alkyl radicals onto the benzimidazole-2-position occurred in high
      yields (63-70 %) when quaternising the pyridine-like 3-N of imidazole with
      camphorsulfonic acid and using large excesses of the azo-initiator, 1,1'
      azobis(cyclohexanecarbonitrile), to supplement the non-chain reaction.
      Elaboration of benzimidazoles to the benzimidazolequinones occurred in excellent
      yields. The IC50 values for the cytotoxicity of benzimidazolequinones towards the
      human skin fibroblast cell line GM00637 were in the nanomolar range, as
      determined by using the MTT assay. The benzimidazolequinones were much more
      cytotoxic than indolequinone analogues. 1,2,3,4-Tetrahydropyrido[1,2
      a]benzimidazole-6,9-dione was the most potent compound prepared being more than
      300 times more cytotoxic than the clinically used bioreductive drug, mitomycin C.
      The latter benzimidazolequinone was more potent under hypoxic conditions
      (associated with solid tumors), being 4.4 times more cytotoxic than under aerobic
      conditions, while mitomycin C was 1.8 times more selective towards hypoxia. The
      cyclopropane fused pyrido[1,2-a]benzimidazolequinone, 1a,2,3,9b-tetrahydro-1H
      cyclopropa[3,4]pyrido[1,2-a]benzimidazole-5,8-dione was less cytotoxic and
      selective than the five-membered ring analogue, 1,1a,8,8a
      tetrahydrocyclopropa[3,4]pyrrolo[1,2-a]benzimidazole-3,6-dione. Modifying the
      structure of the most potent pyrido[1,2-a]benzimidazolequinone by attaching
      methyl substituents onto the quinone moiety increased reductive potentials and
      decreased cytotoxicity and selectivity towards hypoxia.

PMID- 17200922
TI  - A combined computational and experimental approach for the analysis of the
      enantioselective potential of a new macrocyclic receptor for N-protected alpha
      amino acids.
AB  - A new macrocyclic receptor incorporating a thiourea moiety has been synthesised.
      Crystal structures of the macrocycle showed that the receptor has a rigid
      backbone but the thiourea moiety can orientate itself to bind to a DMSO solvent
      molecule. Force-field (MMFFs) calculations were performed to model the macrocycle
      and its binding properties with respect to N-protected amino acids, which were
      measured experimentally by NMR titration. Binding free energies were calculated
      by using the mode integration algorithm (MINTA) or free-energy perturbation
      (FEP). Excellent qualitative agreement with experiment was obtained. To further
      exploit the accuracy of the free-energy predictions for this system, the faster
      free-energy algorithm MINTA was used as a prediction tool to test the binding
      affinity of the macrocycle towards a series of several other amino acid
      derivatives, which speeded up considerably the screening process and reduced
      laboratory costs.

PMID- 17200921
TI  - Recent developments in the metal-catalyzed reactions of metallocarbenoids from
      propargylic esters.
AB  - The transition-metal-catalyzed intramolecular cycloisomerization of propargylic
      carboxylates provides functionalized bicyclo[n.1.0]enol esters in a very
      diastereoselective manner and, depending on the structure, with partial or
      complete transfer of chirality from enantiomerically pure precursors. The
      subsequent methanolysis gives bicyclo[n.1.0] ketones, hence resulting in a very
      efficient two-step protocol for the syntheses of alpha,beta-unsaturated
      cyclopropyl ketones, key intermediates for the preparation of natural products.
      The results from mechanistic computational studies suggest that they probably
      proceed through cyclopropyl metallocarbenoids, formed by endo-cyclopropanation,
      that undergo a 1,2-acyl migration. Finally, the potential of the intermolecular
      reaction and the related pentannulation of propargylic esters bearing pendant
      aromatic rings are also discussed.

PMID- 17200923
TI  - 9-fluorenylphosphines for the Pd-catalyzed sonogashira, suzuki, and Buchwald
      Hartwig coupling reactions in organic solvents and water.
AB  - The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes
      (alkyl=Me, Et, iPr, -Pr, -C18H25) in>95% yields, for which lithiation and
      reaction with R2PCl (R=Cy, iPr, tBu) generates 9-alkyl, 9-PR2-fluorenes which
      constitute electron-rich and bulky phosphine ligands. The in-situ-formed
      palladium-phosphine complexes ([Na2PdCl4], phosphonium salt, base, substrates)
      were tested in the Sonogashira, Suzuki, and Buchwald-Hartwig reactions of aryl
      chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl
      chlorides at 100-120 degrees C leads to>90% yields with 1 mol% of Pd catalyst.
      The Suzuki coupling of aryl chlorides typically requires 0.05 mol% of Pd catalyst
      at 100 degrees C in dioxane for quantitative product formation. To carry out
      "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine
      was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium
      salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble
      catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl
      chlorides can be quantitatively converted into the respective coupling products
      by using 0.1-0.5 mol% of catalyst in pure water at 100 degrees C. Difficult
      substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and
      aryl chlorides are coupled at 100 degrees C by using 0.1-0.5 mol% of catalyst in
      pure water to obtain the respective N-heterocycles in quantitative yields. The
      copper-free aqueous Sonogashira coupling of aryl bromides generates the
      respective tolane derivatives in>95% yield.

PMID- 17200924
TI  - A new class of binuclear gallium hydrides: synthesis and properties of
      [{GaCl(hpp)H}2] (hpp=1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidate).
AB  - Herein we report on the synthesis and characterization of the first
      representative of a new class of gallium hydrides, namely [{GaCl(hpp)H}2]
      (hpp=1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidate). Our X-ray diffraction
      data suggest the presence of weak H--H contacts between adjacent [{GaCl(hpp)H}2]
      molecules in the crystal. With the aid of quantum-chemical calculations, the
      pathway of its formation starting with the adduct H2ClGaNMe3 and the pyrimidine
      hppH were analyzed. [{GaCl(hpp)H}2] slowly decomposes at 25 degrees C, a process
      which presumably leads under H2 elimination to [{GaCl(hpp)}2]. Although we were
      not yet able to characterize [{GaCl(hpp)}2] experimentally, DFT calculations
      provide information about its likely structure. According to these calculations,
      the molecule features a Ga--Ga single bond.

PMID- 17200925
TI  - Cognitive performance in elderly women: significance of the 19bp
      insertion/deletion polymorphism in the 5' flank of the dopamine beta-hydroxylase
      gene, educational level, body fat measures, serum triglyceride, alcohol
      consumption and age.
AB  - BACKGROUND: Genetic and environmental factors influence cognitive aging. The gene
      encoding dopamine beta-hydroxylase (DBH) could be one such factor since this
      hydroxylase converts dopamine to norepinephrine both of which are involved in
      cognition regulation. OBJECTIVE: To assess the effect of the 19bp
      insertion/deletion polymorphism in the 5' flank of the DBH gene on cognitive
      performance in elderly women relative to other factors of cognitive aging.
      METHODS: We examined a cross-sectional sample of 1371 postmenopausal women.
      Cognitive abilities were assessed by the 6-item orientation-memory-concentration
      test. The 19bp insertion/deletion polymorphism of the DBH gene was genotyped and
      apolipoprotein E (APOE) epsilon4 allele status was determined. In addition blood
      pressure, body fat mass and blood lipids were measured. Information was also
      obtained by personal interviews. Data were analyzed by regression analysis.
      RESULTS: Cognition was univariately associated with DBH genotype (p = 0.04). A
      univariate association of borderline significance was observed for APOE epsilon4
      allele status (p = 0.07). Exclusion of women with severe cognition impairment did
      not alter the strength of the association with the DBH gene polymorphism markedly
      (p = 0.06) but obliterated the weak association between APOE epsilon4 allele
      status and cognition. The association of the DBH gene polymorphism with cognition
      persisted after adjustment for other variables (p = 0.03). CONCLUSIONS: The 19bp
      insertion/deletion polymorphism of the DBH gene influences cognition in elderly
      women and might have a stronger effect than APOE epsilon4 allele status on mild
      cognitive impairment. Both genetic polymorphisms had a significantly smaller
      impact on cognition than age, education, alcohol consumption and body fat
      measures.

PMID- 17200926
TI  - Osmium(II) and ruthenium(II) arene maltolato complexes: rapid hydrolysis and
      nucleobase binding.
AB  - Density functional calculations show that aquation of [Os(eta6-arene)(XY)Cl]n+
      complexes is more facile for complexes in which XY=an anionic O,O-chelated ligand
      compared to a neutral N,N-chelated ligand, and the mechanism more dissociative in
      character. The O,O-chelated XY=maltolato (mal) [M(eta6-p-cym)(mal)Cl] complexes,
      in which p-cym=p-cymene, M=OsII (1) and RuII (2), were synthesised and the X-ray
      crystal structures of 1 and 22 H2O determined. Their hydrolysis rates were rapid
      (too fast to follow by NMR spectroscopy). The aqua adduct of the OsII complex 1
      was 1.6 pKa units more acidic than that of the RuII complex 2. Dynamic NMR
      studies suggested that O,O-chelate ring opening occurs on a millisecond timescale
      in coordinating proton-donor solvents, and loss of chelated mal in aqueous
      solution led to the formation of the hydroxo-bridged dimers [(eta6-p-cym)M(mu
      OH)3M(eta6-p-cym)]+. The proportion of this dimer in solutions of the OsII
      complex 1 increased with dilution and it predominated at micromolar
      concentrations, even in the presence of 0.1 M NaCl (conditions close to those
      used for cytotoxicity testing). Although 9-ethylguanine (9-EtG) binds rapidly to
      Os(II) in 1 and more strongly (log K=4.4) than to RuII in 2 (log K=3.9), the OsII
      adduct [Os(eta6-p-cym)(mal)(9EtG)]+ was unstable with respect to formation of the
      hydroxo-bridged dimer at micromolar concentrations. Such insights into the
      aqueous solution chemistry of metal-arene complexes under biologically relevant
      conditions will aid the rational design of organometallic anticancer agents.

PMID- 17200927
TI  - Well-defined cationic alkyl- and alkoxide-aluminum complexes and their reactivity
      with epsilon-caprolactone and lactides.
AB  - We describe the synthesis, structure, and reactivity of low-coordinate Al-alkyl
      and -alkoxide cationic complexes incorporating the sterically bulky
      aminophenolate bidentate ligand 6-(CH(2)NMe(2))-2-CPh(3)-4-Me-C(6)H(2)O- (N,O).
      These complexes are derived from the ionization of neutral dialkyl Al complexes
      (N,O)Al2) (1 a, R=Me; 1 b, R=iBu), readily obtained by alkane elimination between
      AlR3 and the corresponding aminophenol ligand, with the alkyl abstracting
      reagents B(C(6)F(5))3 and [Ph(3)C][B(C(6)F(5))4]. The reactions of 1 a,b with
      B(C(6)F(5))3 yield complicated mixtures or decomposition products, however the
      ionization of the Al-diisobutyl derivative 1 b with [Ph(3)C][B(C(6)F(5))4]
      affords a stable four-coordinate Al-PhBr cationic adduct [(N,O)Al(iBu)(PhBr)]+
      (3+), as deduced from elemental analysis data. Complex 3+ readily coordinates
      Lewis bases such as THF to form the corresponding adduct [(N,O)Al(iBu)(thf)]+
      (4+), and also rapidly chain-transfers with 1-hexene to yield the three
      coordinate Al-hexyl cation [(N,O)Al-hexyl]+ (5+). Both cations 3+ and 5+ slowly
      dimerize to form unprecedented organoaluminum dications [(N,O)AlR+]2 (3'++,
      R=iBu; 5'++, R=hexyl) as deduced from X-ray crystallographic analysis. Cation 3+
      reacts quickly with iPrOH to form a stable Lewis acid/base adduct
      [(N,O)Al(iBu)(HOiPr)]+ (6+), which constitutes the first X-ray characterized
      adduct between an Al-alkyl complex and a simple ROH. The Al-ROH proton in 6+ is
      readily abstracted by NMe(2)Ph to form the neutral isopropoxide Al complex
      [(N,O)Al(iBu)(OiPr)] (7). Upon reaction with THF, cation 6+ undergoes an
      intramolecular proton transfer to yield the ammonium Al-THF complex [(eta1
      HN,O)Al(iBu)(OiPr)(thf)] (8 b+), in which the aminophenolate is eta1-coordinated
      to the Al center. Cation 8 b+ can then be converted to the desired Al-alkoxide
      derivative [(N,O)Al(OiPr)(thf)](+) (10+), by an intramolecular protonolysis
      reaction, as confirmed by X-ray crystallography. The synthesized Al-alkyl cations
      form robust four-coordinate adducts in the presence of cyclic esters such as
      epsilon-caprolactone and (D,L)-lactide, but no insertion chemistry occurs,
      illustrating the poor ability of the Al-R+ moiety to ring-open. In contrast, the
      Al-alkoxide cation 10+ polymerizes epsilon-caprolactone in a controlled manner
      with excellent activity, but is inactive in the polymerization of (D,L)-lactide
      and L-lactide. Control experiments with L-lactide show that cation 10+ ring-opens
      L-lactide to yield a robust five-coordinated Al--lactate cation [(N,O)Al(eta2-L
      lactate-OiPr)(thf)]+ (13+), derived from a monoinsertion of L-lactide into the Al
      -OiPr bond of 10+, that does not further react. Cation 13+ may be regarded as a
      structurally characterized close mimic of the initial intermediate in the ring
      opening polymerization (ROP), of lactides by [{LX}M(OR)(L)] (where LX-=bidentate
      monoanionic ligand and L=labile ligand) metal complex initiators.

PMID- 17200928
TI  - Contraction process of an electroactive actuator based on a one microsecond
      atomistic molecular dynamics simulation.
AB  - The contraction process of an electroactive actuator constituted by calix[4]arene
      units and quaterthiophene segments has been investigated at the microscopic level
      by using atomistic molecular dynamics simulations in dichloromethane solution
      using explicit solvent molecules. Results derived from a 1 mus trajectory of the
      oxidized and deprotonated actuator indicate that the contraction occurs through a
      non-concerted mechanism in which each actuating units present in the system
      behave independently. The efficiency of the contraction process can be reduced by
      the presence of secondary conformational transitions in the calix[4]arene
      scaffolds. Accordingly, the drastic reduction of the molecular length expected
      during the contraction process can be limited by such transitions, which involve
      the rotational isomerism of a phenolate ring. However, such type of
      conformational transitions does not compromise the actuator power due to its
      intrinsic capacity to adopt compact molecular arrangements. On the other hand,
      the rate of the contraction process is influenced by the presence of solvent
      molecules, which have been found to reduce it by a factor of about 1000.

PMID- 17200929
TI  - Structure and bonding in cyclic isomers of BAl2Hnm (n=3-6, m=-2 to +1):
      preference for planar tetracoordination, pyramidal tricoordination, and
      divalency.
AB  - The structure and energetics of cyclic BAl2Hnm (n=3-6, m=-2 to +1), calculated at
      the B3LYP/6-311+G** and QCISD(T)/6-311++G** levels, are compared with their
      corresponding homocyclic boron and aluminium analogues. Structures in which the
      boron and aluminium atoms have coordination numbers of up to six are found to be
      minima. There is a parallel between structure and bonding in isomers of BAl2H(3)2
      and BSi2H3. The number of structures that contain hydrogens out of the BAl2 ring
      plane is found to increase from BAl2H3(2-) to BAl2H6+. Double bridging at one
      bond is common in BAl2H5 and BAl2H6+. Similarly, species with lone pairs on the
      divalent boron and aluminium atoms are found to be minima on the potential energy
      surface of BAl2H(3)2-. BAl2H4- (2 b) is the first example of a structure with
      planar tetracoordinate boron and aluminium atoms in the same structure. Bridging
      hydrogen atoms on the B--Al bond prefer not to be in the BAl2 plane so that the
      pi MO is stabilised by pi-sigma mixing. This stabilisation increases with
      increasing number of bridging hydrogen atoms. The order of stability of the
      individual structures is decided by optimising the preference for lower
      coordination at aluminium, a higher coordination at boron and more bridging
      hydrogen atoms between B--Al bonds. The relative stabilisation energy (RSE) for
      the minimum energy structures of BAl2Hnm that contain pi-delocalisation are
      compared with the corresponding homocyclic aluminium and boron analogues.

PMID- 17200930
TI  - The crystal structure of anhydrous beta-caffeine as determined from X-ray powder
      diffraction data.
AB  - The crystal structure of the low-temperature form of anhydrous caffeine has been
      determined by using X-ray powder-diffraction data with a combined simulated
      annealing/Rietveld method. Anhydrous caffeine crystallizes with five
      crystallographically independent molecules in a monoclinic C-centred unit cell
      with dimensions of a=43.0390(17), b=15.0676(6) and c=6.95314(14) A and a beta
      angle of 99.027(2) degrees.

PMID- 17200931
TI  - Classical and distonic radical cations: a valence bond approach.
AB  - The conventional radical cations arising from the ionization of CH(3)CH(2)X (X=F,
      OH, NH(2), Cl, SH, PH(2)), and their distonic isomers, CH(2)CH(2)XH(.+), were
      studied by means of standard Moller-Plesset and G2 methods, and by an ab initio
      valence bond method. Among the conventional structures, two distinct states are
      considered. In the so-called c' states, the unpaired electron is in an orbital
      that lies in the plane of the heavy atoms, while the c'' states have their
      unpaired electron in an orbital lying out of the plane. It is shown that c'
      states are, as a rule, more stable than the c'' states, by up to approximately 20
      kJ mol(-1) depending on the nature of X, owing to a stabilizing interplay of
      resonating structures. While the geometries of the c'' states are rather similar
      to those of the neutral molecules, some of the c' states display very different
      geometries, characterized by elongated C--C bonds, particularly when X=F or, to a
      lesser extent, when X=OH or Cl. These peculiar geometric features are
      rationalized by the valence bond analysis, which reveals that the C--C bond in
      these species is better viewed as a two-center, one-electron bond. The distonic
      radical cations are generally more stable than the conventional ones (by 20-100
      kJ mol(-1)), except for the less electronegative X groups of the series, namely
      X=SH and PH(2). In these two cases, together with X=NH(2), the radical cation
      displays a classical distonic structure, as regards the geometry and electronic
      state. On the other hand, considerable C--X elongation is found for X=F or Cl. In
      these last cases, the valence bond analysis shows that the radical cation is
      better viewed as an ion-molecule complex between an ionized ethylene and a
      neutral HX molecule. The electronic structure of the distonic radical cation with
      X=OH lies between the two previous limiting descriptions.

PMID- 17200932
TI  - On a possible growth mechanism for polycyclic aromatic hydrocarbon di-cations:
      C(7)H(6)(2+) + C(2)H(2).
AB  - The mechanism of the bond-forming reaction between C(7)H(6) (2+) and C(2)H(2) to
      yield C(9) entities has been investigated by density functional theory
      calculations with close comparison with experimental data. It is shown that the
      reaction produces the C(9)H(6) (2+) and C(9)H(7) (2+) di-cations with geometries
      most probably derived from the indene skeleton. In comparison, the formation of
      linear structures of di-cations is much more energy-demanding and therefore
      appears improbable.

PMID- 17200933
TI  - The combined catalytic action of solid acids with nickel for the transformation
      of polypropylene into carbon nanotubes by pyrolysis.
AB  - The effects of both organically modified montmorillonite (OMMT) and Ni(2)O(3) on
      the carbonization of polypropylene (PP) during pyrolysis were investigated. The
      results from TEM and Raman spectroscopy showed that the carbonized products of PP
      were mainly multiwalled carbon nanotubes (MWNTs). Surprisingly, a combination of
      OMMT and Ni(2)O(3) led to high-yield formation of MWNTs. X-ray powder diffraction
      (XRD) and GC-MS were used to investigate the mechanism of this combination for
      the high-yield formation of MWNTs from PP. Bronsted acid sites were created in
      degraded OMMT layers by thermal decomposition of the modifiers. The resultant
      carbenium ions play an important role in the carbonization of PP and the
      formation of MWNTs. The degradation of PP was induced by the presence of
      carbenium ions to form predominantly products with lower carbon numbers that
      could be easily catalyzed by the nickel catalyst for the growth of MWNTs.
      Furthermore, carbenium ions are active intermediates that promote the growth of
      MWNTs from the degradation products with higher carbon numbers through hydride
      transfer reactions. The XRD measurements showed that Ni(2)O(3) was reduced into
      metallic nickel (Ni) in situ to afford the active sites for the growth of MWNTs.

PMID- 17200934
TI  - Simple bis-thiocarbono-hydrazones as sensitive, selective, colorimetric, and
      switch-on fluorescent chemosensors for fluoride anions.
AB  - Bis-thiocarbono-hydrazones are found to be a class of sensitive, selective,
      ratiometric, and colorimetric chemosensors for anions such as fluoride (F(-)) or
      acetate (Ac(-)). The sensitivities, or the binding constants of the sensors with
      anions, were found to be strongly dependent on the substituents appended on the
      pi-conjugation framework, the delocalization bridge CH==N, the aromatic moiety,
      and the hetero atom in the C==X group (X=O, S) of the sensors. Single-crystal
      structures and (1)H NMR titration analysis shows that the --CH==N-- moiety is a
      hydrogen-bond donor, and it is proposed that an additional CHF hydrogen bond is
      formed for the sensors in the presence F(-). A sensor bearing anthracenyl groups
      is demonstrated as a switch-on fluorescent chemosensor for F(-) and Ac(-). The
      recognition of F(-) in acetonitrile (MeCN) by a sensor with nitrophenyl
      substituents is tolerant to MeOH (MeCN/MeOH=10:1, v/v) and water
      (MeCN/H(2)O=30:1, v/v); at these solvent ratios the absorption intensity of the
      sensor-F(-) complex solution at maximal absorption wavelength was attenuated to
      half of the original value in pure MeCN.

PMID- 17200935
TI  - A color version of the Hinsberg test: 1 degrees -3 degrees amine indicator.
AB  - The Hinsberg test to recognize the type of amine (1 degrees -3 degrees amines),
      which has been established for more than 100 years and well documented in
      textbooks, is not possible without conducting complicated organic reactions. We
      report for the first time unique chemosensors that are capable of showing
      selective color changes toward 1 degrees -3 degrees amines as a color version of
      the Hinsberg test. This simple and straightforward qualitative analysis, using
      the synthesized novel compounds herein, can be considered a new innovative tool
      for discriminating 1 degrees -3 degrees amines as an alternative to the
      historical Hinsberg test.

PMID- 17200936
TI  - Morphology, mechanisms and pathology of musculoskeletal ageing.
AB  - In general terms, the recognized alterations in circulating humoral factors
      (hormones, cytokines, growth factors) that occur in ageing, coupled with innate
      cellular senescence exaggerated by the slow turnover of many connective tissue
      cell populations and the age-associated alterations in matrix molecule cross
      linking, predispose the elderly to altered connective tissue biology. These
      changes can be profound, leading to poor mobility, altered ability to withstand
      cold, weakness and an increased risk of falls, fractures and age-associated
      'degenerative' diseases, such as osteoarthritis and osteoporosis. As
      understanding of the causes of altered connective tissue function with age
      increases, it is becoming clearer that many of the predisposing factors (growth
      hormone, cytokines, load/life style) are potential targets for improving quality
      of life in the elderly.

PMID- 17200937
TI  - The aged breast.
AB  - There is a clear association between the development of breast cancer and
      increasing age, with 80% of cancers occurring in women more than 50 years of age
      and one-third in women over 70 years. Following the menopause the breast
      undergoes involution, with the main changes affecting the terminal ductal lobular
      unit. There is an increase in oestrogen receptor alpha (ERalpha)-positive cells,
      a decrease in proliferation but, in comparison to premenopausal breasts, a
      greater number of ERalpha-proliferating cells. The breast cancers that occur in
      women >/= 75 years are more likely to be ER-positive, with a low growth rate and
      limited expression of HER-2 and p53. It is proposed that uneven involution of the
      breast, the persistence of at-risk lesions, the presence of ERalpha-proliferating
      cells and local oestrogen metabolism in breast adipose tissue are factors in the
      development of breast cancers with a well-differentiated phenotype.

PMID- 17200938
TI  - The ageing male reproductive tract.
AB  - Ageing of the male reproductive system is characterized by changes in the
      endocrine system, hypogonadism, erectile dysfunction and proliferative disorders
      of the prostate gland. Stochastic damage accumulating within ageing leads to
      progressive dysregulation at each level of the hypothalamic-pituitary-gonadal
      (HPG) axis and in local auto/paracrine interactions, thereby inducing
      morphological changes in reproductive target organs, such as the prostate, testis
      and penis. Despite age-related changes in the HPG axis, endocrine functions are
      generally sufficient to maintain fertility in elderly men. Ageing of the male
      reproductive system can give rise to clinically relevant manifestations, such as
      benign prostatic hyperplasia (BPH), prostate cancer (PCa) and erectile
      dysfunction (ED). In this review, we discuss morphological/histological changes
      occurring in these organs and current views and concepts of the underlying
      pathology. Moreover, we emphasize the molecular/cellular pathways leading to
      reduced testicular/penile function and proliferative disorders of the prostate
      gland.

PMID- 17200939
TI  - The endocrine system and ageing.
AB  - Complex changes occur within the endocrine system of ageing individuals. This
      article explores the changes that occur in the metabolism and production of
      various hormones and discusses the resulting clinical consequences. As
      individuals age there is a decline in the peripheral levels of oestrogen and
      testosterone, with an increase in luteinizing hormone, follicle-stimulating
      hormone and sex hormone-binding globulin. Additionally there is a decline in
      serum concentrations of growth hormone, insulin-like growth factor-I and
      dehydroepiandrosterone and its sulphate-bound form. Even though there are complex
      changes within the hypothalmo-pituitary-adrenal/thyroid axis, there is minimal
      change in adrenal and thyroid function with ageing. The clinical significance of
      these deficiencies with age are variable and include reduced protein synthesis,
      decrease in lean body mass and bone mass, increased fat mass, insulin resistance,
      higher cardiovascular disease risk, increase in vasomotor symptoms, fatigue,
      depression, anaemia, poor libido, erectile deficiency and a decline in immune
      function. For each endocrine system, studies have been carried out in an attempt
      to reverse the effects of ageing by altering the serum hormonal levels of older
      individuals. However, the real benefits of hormonal treatment in older
      individuals are still being evaluated.

PMID- 17200940
TI  - Ageing of the conduit arteries.
AB  - Conduit arteries become stiffer with age due to alterations in their morphology
      and the composition of the their major structural proteins, elastin and collagen.
      The elastic lamellae undergo fragmentation and thinning, leading to ectasia and a
      gradual transfer of mechanical load to collagen, which is 100-1000 times stiffer
      than elastin. Possible causes of this fragmentation are mechanical (fatigue
      failure) or enzymatic (driven by matrix metallo proteinases (MMP) activity), both
      of which may have genetic or environmental origins (fetal programming).
      Furthermore, the remaining elastin itself becomes stiffer, owing to calcification
      and the formation of cross-links due to advanced glycation end-products (AGEs), a
      process that affects collagen even more strongly. These changes are accelerated
      in the presence of disease such as hypertension, diabetes and uraemia and may be
      exacerbated locally by atherosclerosis. Raised MMP activity, calcification and
      impaired endothelial function are also associated with a high level of plasma
      homocysteine, which itself increases with age. Impaired endothelial function
      leads to increased resting vascular smooth muscle tone and further increases in
      vascular stiffness and mean and/or pulse pressure. The effect of increased
      stiffness, whatever its underlying causes, is to reduce the reservoir/buffering
      function of the conduit arteries near the heart and to increase pulse wave
      velocity, both of which increase systolic and pulse pressure. These determine the
      peak load on the heart and the vascular system as a whole, the breakdown of
      which, like that of any machine, depends more on the maximum loads they must bear
      than on their average. Reversing or stabilising the increased arterial stiffness
      associated with age and disease by targeting any or all of its causes provides a
      number of promising new approaches to the treatment of systolic hypertension and
      its sequelae, the main causes of mortality and morbidity in the developed world.

PMID- 17200941
TI  - p53: at the crossroad between cancer and ageing.
AB  - The p53 tumour suppressor plays an undisputed role in cancer. p53's tumour
      suppressive activity stems from its ability to respond to a variety of stresses
      to trigger cell cycle arrest, apoptosis or senescence, thereby protecting against
      malignant transformation. An increasing body of evidence suggests that p53 also
      drives organismal ageing. Although genetic models with altered p53 function
      display age-related phenotypes and thus provide in vivo evidence that p53
      contributes to the ageing process, p53's role in organismal ageing remains
      controversial. Anti-cancer therapies that target p53 and reactivate or enhance
      its activity are considered good alternatives for treating various neoplasms.
      Therefore, it is important to determine whether these clinical approaches
      compromise tissue homeostasis and contribute to ageing. This review presents a
      number of models with altered p53 function and discusses how these models
      implicate p53 as part of a molecular network that integrates tumour suppression
      and ageing.

PMID- 17200942
TI  - Skin ageing and its treatment.
AB  - The effects of chronic sun exposure on skin are readily apparent when skin not
      typically exposed to the sun and skin regularly exposed to the sun are compared.
      While the sun is not the only aetiological factor in the dynamic process of skin
      ageing, it is the primary exogenous cause among several internal and
      environmental elements. Thus, photo-ageing, the main focus of this article, is a
      subset of extrinsic skin ageing. The influence of the sun in extrinsic skin
      ageing, as well as its role in potentially altering the normal course of
      intrinsic (also known as natural or cellular) ageing, is discussed. Telomeres,
      the specialized structures found at the ends of chromosomes, are believed to be
      integral to cellular ageing as well as in the development of cancer. The ageing
      process, both intrinsic and extrinsic, is also believed to be influenced by the
      formation of free radicals, also known as reactive oxygen species. The loss of
      collagen is considered the characteristic histological finding in aged skin.
      Wrinkling and pigmentary changes are directly associated with photo-ageing and
      are considered its most salient cutaneous manifestations. Such photodamage
      represents the cutaneous signs of premature ageing. In addition, deleterious
      consequences of chronic sun exposure, specifically various forms of photo-induced
      skin cancer, are also linked to acute and chronic sun exposure. The only known
      strategies aimed at preventing photo-ageing include sun avoidance, using
      sunscreens to block or reduce skin exposure to UV radiation, using retinoids to
      inhibit collagenase synthesis and to promote collagen production, and using anti
      oxidants, particularly in combination, to reduce and neutralize free radicals.

PMID- 17200943
TI  - Reproductive ageing in women.
AB  - The traditional view in respect to female reproduction is that the number of
      oocytes at birth is fixed and continuously declines towards the point when no
      more oocytes are available after menopause. In this review we briefly discuss the
      embryonic development of female germ cells and ovarian follicles. The ontogeny of
      the hypothalamic-pituitary-gonadal axis is then discussed, with a focus on
      pubertal transition and normal ovulatory menstrual cycles during female adult
      life. Biochemical markers of menopausal transition are briefly examined. We also
      examine the effects of age on female fertility, the contribution of chromosomal
      abnormalities of the oocyte to the observed decline in female fertility with age
      and the possible biological basis for the occurrence of such abnormalities.
      Finally, we consider the effects of maternal age on obstetric complications and
      perinatal outcome. New data that have the potential to revolutionize our
      understanding of mammalian oogenesis and follicular formation, and of the female
      reproductive ageing process, are also briefly considered.

PMID- 17200944
TI  - Renal ageing.
AB  - The function of the kidney, as well as its morphology, changes markedly with age.
      The glomerular filtration rate falls progressively, independent of overt
      pathology. Glomerular, vascular and accompanying parenchymal changes occur and
      other disorders associated with ageing, such as diabetes and hypertension, have a
      stochastic deleterious effect on both form and function. Declining renal function
      with age has important implications, not only for individual homeostasis but also
      for the use of drug therapy and for the receipt and donation of organs for
      transplantation. Molecular mechanisms and cellular changes underlying some of the
      functional and structural changes associated with ageing are becoming clearer, as
      are some of the ways in which genetic background, age and disease can combine to
      produce functional damage.

PMID- 17200945
TI  - Ageing and hearing loss.
AB  - Although many adults retain good hearing as they age, hearing loss associated
      with ageing is common among elderly persons. There are a number of
      pathophysiolological processes underlying age-related changes to functional
      components in the inner ear. Genetic factors determine the ageing process but are
      under the influence of intrinsic and environmental factors. It is difficult to
      distinguish changes of normal ageing from those of other contributing factors.
      The effects of age-related deafness can have significant physical, functional and
      mental health consequences. Although a deficit in hearing can be corrected to
      some degree by a hearing aid or other appropriate amplification devices, hearing
      related rehabilitative needs are much more than simply amplifying external sound.
      Only by better understanding the process of ageing and its effect on the auditory
      function can we better accommodate elderly people in our day-to-day interactions.
      We review here the structure and function of the inner ear, pathophysiology
      associated with age-related hearing loss (ARHL), heritability, allelism and
      modifier genes of ARHL, and evaluate the genetic analyses for identification of
      genetic factors that are involved.

PMID- 17200947
TI  - Autophagy, organelles and ageing.
AB  - As a result of insufficient digestion of oxidatively damaged macromolecules and
      organelles by autophagy and other degradative systems, long-lived postmitotic
      cells, such as cardiac myocytes, neurons and retinal pigment epithelial cells,
      progressively accumulate biological 'garbage' ('waste' materials). The latter
      include lipofuscin (a non-degradable intralysosomal polymeric substance),
      defective mitochondria and other organelles, and aberrant proteins, often forming
      aggregates (aggresomes). An interaction between senescent lipofuscin-loaded
      lysosomes and mitochondria seems to play a pivotal role in the progress of
      cellular ageing. Lipofuscin deposition hampers autophagic mitochondrial turnover,
      promoting the accumulation of senescent mitochondria, which are deficient in ATP
      production but produce increased amounts of reactive oxygen species. Increased
      oxidative stress, in turn, further enhances damage to both mitochondria and
      lysosomes, thus diminishing adaptability, triggering mitochondrial and lysosomal
      pro-apoptotic pathways, and culminating in cell death.

PMID- 17200949
TI  - The pathology of ageing: concepts and mechanisms.
AB  - The rising numbers and proportion of aged individuals in the population is a
      global demographic trend. The diseases associated with ageing are becoming more
      prevalent, and the associated healthcare costs are having a significant economic
      impact in all countries. With these changes have come great advances in our
      understanding of the mechanisms of ageing. The mechanisms of cellular ageing at a
      genetic, protein and organelle level are becoming clearer, as are some of the
      more complex associations between environment and ageing. System ageing is also
      becoming better understood, and the potential biological advantages of ageing are
      being explored. Many of the advances in these fields are opening up the prospect
      of targeted therapeutic intervention for ageing and age related disease.

PMID- 17200948
TI  - Hallmarks of telomeres in ageing research.
AB  - Telomeres are repetitive DNA sequences at the ends of linear chromosomes.
      Telomerase, a cellular reverse transcriptase, helps maintain telomere length in
      human stem cells, reproductive cells and cancer cells by adding TTAGGG repeats
      onto the telomeres. However, most normal human cells do not express telomerase
      and thus each time a cell divides some telomeric sequences are lost. When
      telomeres in a subset of cells become short (unprotected), cells enter an
      irreversible growth arrest state called replicative senescence. Cells in
      senescence produce a different constellation of proteins compared to normal
      quiescent cells. This may lead to a change in the homeostatic environment in a
      tissue-specific manner. In most instances cells become senescent before they can
      become cancerous; thus, the initial growth arrest induced by short telomeres may
      be thought of as a potent anti-cancer protection mechanism. When cells can be
      adequately cultured until they reach telomere-based replicative senescence,
      introduction of the telomerase catalytic protein component (hTERT) into
      telomerase-silent cells is sufficient to restore telomerase activity and extend
      cellular lifespan. Cells with introduced telomerase are not cancer cells, since
      they have not accumulated the other changes needed to become cancerous. This
      indicates that telomerase-induced telomere length manipulations may have utility
      for tissue engineering and for dissecting the molecular mechanisms underlying
      genetic diseases, including cancer.

PMID- 17200950
TI  - Ageing and the brain.
AB  - In this review, the evidence for changes in the human brain with ageing at both
      the macroscopic and microscopic levels is summarized. Loss of neurons is now
      recognized to be more modest than initial studies suggested and only affects some
      neuron populations. Accompanying loss of neurons is some reduction in the size of
      remaining neurons. This reflects a reduced size of dendritic and axonal
      arborizations. Some of the likely causes of these changes, including free radical
      damage resulting from a high rate of oxidative metabolism in neurons, glycation
      and dysregulation of intracellular calcium homeostasis, are discussed. The roles
      of genes and environmental factors in causing and responding to ageing changes
      are explored.

PMID- 17200946
TI  - Immunosenescence of ageing.
AB  - Ageing is a complex process that negatively impacts the development of the immune
      system and its ability to function. The mechanisms that underlie these age
      related defects are broad and range from defects in the haematopoietic bone
      marrow to defects in peripheral lymphocyte migration, maturation and function.
      The thymus is a central lymphoid organ responsible for production of naive T
      cells, which play a vital role in mediating both cellular and humoral immunity.
      Chronic involution of the thymus gland is thought to be one of the major
      contributing factors to loss of immune function with increasing age. It has
      recently been demonstrated that thymic atrophy is mediated by a shift from a
      stimulatory to a suppressive cytokine microenvironment. In this review we present
      an overview of the morphological, cellular and biochemical changes that have been
      implicated in the decline of thymic and peripheral immune function with ageing.
      We conclude with the clinical implications of age-associated immunosenescence to
      vaccine development for tumours and infectious disease. A fundamental
      understanding of the complex mechanisms by which ageing attenuates immune
      function will enable translational research teams to develop new therapies and
      vaccines specifically aimed at overcoming these defects in immunological function
      in the aged.

PMID- 17200951
TI  - Reprogramming of genetic networks during initiation of the Fetal Alcohol
      Syndrome.
AB  - Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from
      maternal alcohol use. We used a non a priori approach to prioritize candidate
      pathways during alcohol-induced teratogenicity in early mouse embryos. Two
      C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams
      with alcohol (2x 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a
      higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg)
      significantly protected B6J embryos but slightly promoted FASD in B6N embryos.
      Microarray transcript profiling was performed on the embryonic headfold 3 hr
      after the first maternal alcohol injection (GEO data series accession GSE1074).
      This analysis revealed metabolic and cellular reprogramming that was substrain
      specific and/or PK11195-dependent. Mapping ethanol-responsive KEGG (Kyoto
      Encyclopedia of Genes and Genomes) pathways revealed down-regulation of ribosomal
      proteins and proteasome, and up-regulation of glycolysis and pentose phosphate
      pathway in B6N embryos; and significant up-regulation of tight junction, focal
      adhesion, adherens junction, and regulation of the actin cytoskeleton (and near
      significant up-regulation of Wnt signaling and apoptosis) pathways in both
      substrains. Expression networks constructed computationally from these altered
      genes identified entry points for EtOH at several hubs (MAPK1, ALDH3A2, CD14,
      PFKM, TNFRSF1A, RPS6, IGF1, EGFR, PTEN) and for PK11195 at AKT1. Our findings are
      consistent with the growing view that developmental exposure to alcohol alters
      common signaling pathways linking receptor activation to cytoskeletal
      reorganization. The programmatic shift in cell motility and metabolic capacity
      further implies cell signals and responses that are integrated by the
      mitochondrial recognition site for PK11195.

PMID- 17200952
TI  - Differential susceptibility of leukocyte subsets to cytotoxic T cell killing:
      implications for HIV immunopathogenesis.
AB  - BACKGROUND: Cytotoxic T lymphocytes (CTL) are crucial for the host defense
      against viral infection. In many cases, this anti-viral immune response
      contributes to host pathogenesis, through inflammation and tissue destruction.
      Few studies have explored the relative susceptibility of infected cells to CTL
      killing, and the range of cell types that may be effectively killed by CTLs in
      vivo, both of which are key to understanding both immune control of infection and
      immune-related pathogenesis. METHODS: We developed and optimized a highly
      sensitive method to quantify the relative susceptibility of leukocyte subsets to
      CTL-mediated killing. Maximal sensitivity was achieved by uniquely measuring cell
      death occurring during the assay culture. RESULTS: We found that leukocyte
      subsets have a wide range of susceptibility to antigen-specific CTL-mediated
      lysis. Generally, T cells were more susceptible than B or NK cells, with CD4 T
      cells being more susceptible than CD8 T cells. In all lymphocyte lineages,
      susceptibility was greater for more differentiated subsets compared with their
      naive counterparts; however, for dendritic cells, immature cells are more
      susceptible than mature cells. We focused on the susceptibility of T cell
      subsets, and found that naive cells are far more resistant than memory cells, and
      in particular, CCR5+ or HLA-DR+ memory cells are highly susceptible to CTL
      mediated killing. CONCLUSIONS: These results provide an explanation for the
      observation that certain subsets of CD4 T cells are ablated during chronic HIV
      infection, and indicate which subsets are most likely to contain the persistent
      viral reservoir.

PMID- 17200953
TI  - Automated laser scanning cytometry: a powerful tool for multi-parameter analysis
      of drug-induced apoptosis.
AB  - BACKGROUND: Simultaneous analysis of multiple intracellular events is critical
      for assessing the effect of biological response modifiers, including the efficacy
      of chemotherapy. Here we used the automated laser scanning cytometry (LSC) for
      multi-parameter analysis of drug-induced tumor cell apoptosis. MATERIALS: Using 2
      mercaptopyridine-N-oxide-hydrate sodium salt, or the commonly used
      chemotherapeutic agents etoposide and camptothecin, we performed simultaneous
      analyses of apoptosis-related morphological features as well as fluorescence
      based biochemical changes in a 96-well format. RESULTS: We demonstrate the scope
      of LSC as a platform for comparing multiple variables between different cell
      populations, distinguishing unique events at a single cell level within a sample
      population, and enabling simultaneous screenings in a single assay at multiple
      dosages and time-points. CONCLUSION: These data underscore the power of LSC for
      simultaneous multi-parameter analysis, which could have implications for
      screening or assessing the efficacy of drug responses in heterogeneous cell
      populations and at the single cell level.

PMID- 17200954
TI  - Simultaneous analysis of steady-state intracellular pH and cell morphology by
      automated laser scanning cytometry.
AB  - BACKGROUND: Cytosolic pH (pHi) changes are critical in cellular response to
      diverse stimuli, including cell survival and death signaling. The potential
      drawback in flow-based analysis is the inability to simultaneously visualize the
      cells during pHi measurements. Here, the suitability of laser scanning cytometer
      (LSC) in pHi measurement was investigated. AIM: Using the two extensively
      reported pH-sensitive fluorescent probes, 2,7-bis(2-Carboxyethyl)-5(6)
      carboxyfluorescein acetoxymethyl ester (BCECF-AM) and 5-(and-6)-carboxy SNARF-1
      acetoxymethyl ester, we evaluated the potential of automated LSC as a platform
      for simultaneous determination of pHi and cell morphology. The effect of a
      variety of buffer systems-commonly employed for pHi measurements-on cell
      morphology before pH clamping with the ionophore, nigericin, was also assessed.
      METHODS: Measurement of cytosolic pH was performed using pH-sensitive fluorescent
      probes BCECF-AM and SNARF-1. pH clamping was carried out using nigericin and
      samples were analyzed on the LSC or CyAn ADP Flow Cytometer. RESULTS: The pHi
      clamping conditions were optimized as 140 mM potassium and 10 microM nigericin.
      The suitable buffers used for pH clamping: 140 mM KCl, 1 mM MgCl2, 2 mM
      CaCl(2).2H2O, 5 mM glucose, 20 mM MES and 140 mM KCl, 1 mM MgCl2, 2 mM
      CaCl(2).2H2O, 5 mM glucose, and 20 mM Tris. Results obtained with the LSC
      strongly correlated with those obtained by flow cytometry. CONCLUSION: We report
      here that LSC is an excellent and highly reproducible platform for pHi
      determination, and provides the added advantage of simultaneous imaging of cells
      before, during, and after pH measurements.

PMID- 17200956
TI  - Statistical considerations for enumeration of circulating tumor cells.
AB  - BACKGROUND: Circulating tumor cells (CTCs) in patients with carcinomas are
      extremely rare. In metastatic breast cancer, the presence of >or=5 CTCs in 7.5 ml
      of blood has been associated with short survival. As this threshold has clinical
      implications, it is important to recognize the limitations associated with the
      detection and enumeration of CTCs. METHODS: Statistical analyses were performed
      on data generated from a multi-center clinical trial that utilized the
      CellSearchtrade mark System to isolate and enumerate CTCs in 7.5 ml blood
      samples. The statistical issues associated with each step of the process, from
      blood collection to final image analysis and CTC enumeration, were determined and
      implemented into a model. RESULTS: A model describing the statistics of the
      different process steps that are needed for the isolation and detection of CTCs
      was developed. The model uses the Poisson distribution for blood collection and
      empirically determined distributions for the isolation and identification of
      CTCs. The variability between readers was identified as one of the main sources
      of errors responsible for the current threshold level of five CTCs. CONCLUSIONS:
      Elimination of the errors made in the identification of tumor cells isolated from
      7.5 ml of blood could potentially reduce the CTC threshold for the identification
      of patients with a poor prognosis from the current value of five CTCs to one CTC
      per 7.5 ml of blood.

PMID- 17200955
TI  - Increased immunofluorescence sensitivity using 532 nm laser excitation.
AB  - OBJECTIVE: We evaluated the use of a high power, diode pulsed solid-state laser
      emitting 532 nm light for immunofluorescence applications. We compared the
      sensitivity and utility of this laser with the standard 488 nm excitation.
      METHODS: A flow cytometer was equipped with both a 488 nm and a 532 nm laser;
      fluorescence emissions from each laser were collected using the same filters and
      the same detector system. Cells or compensation beads (e.g. latex beads coated
      with anti-kappa antibodies) were stained with monoclonal antibodies conjugated to
      phycoerythrin (PE) as well as the PE tandem dyes TRPE, Cy5PE, Cy5.5PE, and Cy7PE.
      The sensitivity of detection of these reagents as well as those in heavily
      compensated channels was quantified by measuring the spreading error for a
      primary detector into a secondary detector. RESULTS: Measurement of the
      fluorescence emission of PE and PE-tandem dyes was considerably more sensitive
      when using 532 nm excitation (150 mW) as compared with 488 nm excitation (20 mW).
      In addition, as the absolute number of photoelectrons collected was greater,
      there was less measurement-error-induced spread into the compensated channels. As
      an example, when comparing the spreading error of PE labeled cells into the TRPE
      detector, the green laser was found to be 15-fold more sensitive as compared with
      the blue laser. In addition, the blue laser produced more autofluoresent signal
      from cells as compared with the green laser. Together, these advantages of the
      532 nm excitation line provides for a significantly improved detection of
      immunofluorescence staining.

PMID- 17200957
TI  - The use of flow cytometry to study the germination of Bacillus cereus endospores.
AB  - BACKGROUND: At present the study of endospore germination is conducted using
      microbiological methods which are slow and yield data based on the means of large
      heterogeneous populations. Flow cytometry (FCM) offers the potential to rapidly
      quantify and identify germination and outgrowth events for large numbers of
      individual endospores. METHODS: Standard methods were employed to arrest the
      germination of Bacillus cereus endospores at defined stages. Endospores were then
      stained with SYTO 9 alone or carboxyfluorescein diacetate (CFDA) together with
      Hoechst 33342 and analysed using FCM. Comparisons were made between FCM as a
      method to measure germination rate and standard microbiological techniques.
      RESULTS: Germinating endospores displayed increases in permeability to SYTO 9 and
      hydrolysis of CFDA compared with controls. Statistically significant correlations
      were found between the standard plate count method and both FCM methods for
      measuring the percentage of germinating and outgrowing endospores up to 75 min
      after addition of germinant. CONCLUSIONS: Using FCM, the percentage of
      germinating or outgrowing endospores at various time points during germination
      and/or outgrowth can be quantified. FCM with CFDA/Hoechst 33342 staining may be
      used to estimate overall germination rate, whereas FCM with SYTO 9 staining may
      be used to quantify ungerminated, germinating and outgrowing endospores.

PMID- 17200958
TI  - Towards an understanding of apoptosis detection by SYTO dyes.
AB  - BACKGROUND: SYTO probes are gaining momentum as reliable and easy to use markers
      of apoptotic cell death, but the phenomenon underlying reduced SYTO fluorescence
      in apoptotic cells as compared with normal cells is still not fully elucidated.
      Herein, we attempt to provide further insights into mechanisms of reduced SYTO16
      fluorescence during apoptosis. METHODS: Human follicular lymphoma cell lines were
      subjected to diverse apoptotic and oncotic stimuli with subsequent
      multiparametric flow cytometric and fluorescence imaging analysis. SYTO green
      (SYTO11-16), TMRM, PI, 7AAD, and Hoechst 33342 probes were applied for
      multivariate analysis of temporal sequence of apoptotic events. Sorting of cells
      differing in the level of SYTO16 fluorescence and subsequent characterization of
      obtained subpopulations were also performed. RESULTS: Loss of SYTO16 fluorescence
      (SYTOlow/PI+ events) has been observed in cells exposed to oncotic stimuli,
      whereas SYTOhigh/PI+ events did not prevail at any treatment scenario. We tracked
      similarities and discrepancies between SYTO16 and TMRM probes. Often, SYTO16 and
      TMRM exhibited the same staining profiles, as loss of their fluorescence was
      detected in a single cell population. However, both mitochondrial uncoupler FCCP
      and a small-molecule Bcl-2 inhibitor, HA14-1, appeared to induce distinct
      staining profiles of SYTO16 and TMRM, with the decrease in TMRM fluorescence
      preceding the loss of SYTO16 fluorescence. Importantly, in both cases (FCCP and
      HA14-1) the decrease of SYTO16 fluorescence was blocked by pharmacological
      inhibition of caspases (with z-VAD-fmk). CONCLUSIONS: The data demonstrate that
      loss of SYTO16 is caspase-dependent, as is not a mere indicator of Deltapsim
      dissipation. Commonly observed similarities between SYTO and TMRM may stem from
      the fast kinetics of apoptotic events once cell death is initiated.

PMID- 17200959
TI  - New assay using fluorogenic substrates and immunofluorescence staining to measure
      cysteine cathepsin activity in live cell subpopulations.
AB  - BACKGROUND: Cathepsins are endosomal/lysosomal proteases that play important
      roles in regulating cell physiological processes in cardiovascular, neurological,
      musculoskeletal, and immunological systems. Pathophysiological processes are
      often associated with a change in cathepsin expression and activity, leading to
      the possibility of using cathepsins as disease markers for diagnosis and
      prognosis. METHODS: We describe a new assay utilizing an argon laser flow
      cytometer to measure activities of cysteine cathepsins B, L, and S in live cells
      using cell permeable fluorogenic cresyl violet-conjugated peptides as selective
      substrates. Substrate concentration dependency and time kinetics studies were
      performed. The activity assay was combined with immunofluorescence staining to
      detect cell lineage-specific molecules and assess cathepsin activities in a
      heterogeneous cell population. RESULTS: Substrate concentrations utilized were
      not limiting, because MFI significantly increased in a macrophage cell line
      stimulated with bacterial lipopolysaccharide. Selective cathepsin inhibitors
      demonstrated the selectivity of substrate cleavage. Cells fixed and stored before
      analysis had no loss of fluorescence product. Activities of cathepsins B, L and S
      in splenic B cells, T cells and macrophages identified by immunofluorescence
      staining were analyzed. CONCLUSION: This novel technique determines cathepsin
      activities on a per cell basis without requiring purification of different cell
      types from a heterogeneous cell population.

PMID- 17200960
TI  - Treatment of recurrent pulmonary vein stenoses with endovascular stenting and
      adjuvant oral sirolimus.
AB  - The increasing use of radiofrequency catheter ablation for the cure of atrial
      fibrillation has led to iatrogenic pulmonary vein stenosis as a new clinical
      entity. The optimal diagnostic modality and treatment for pulmonary vein stenosis
      and restenosis remain unclear. We report the successful treatment of pulmonary
      vein restenosis following percutaneous balloon angioplasty, and for the first
      time, following surgical bovine pericardial patch angioplasty, with endovascular
      stenting and adjuvant oral sirolimus. Both patients remain asymptomatic at 1 year
      follow-up without evidence of restenosis.

PMID- 17200961
TI  - Factors affecting outcomes after radical cystectomy in African Americans.
AB  - BACKGROUND: Previous studies indicate that African Americans with bladder cancer
      have a worse outcome than Caucasians. Delay in seeking care and higher stage at
      presentation have been cited as possible reasons for the observed differences.
      The authors hypothesized that differences in hospital volume where patients
      undergo radical cystectomy may be responsible for race-based differences in
      outcomes after the procedure. METHODS: The authors analyzed data from the Health
      Care Cost and Utilization Project and identified 4862 patients who had undergone
      radical cystectomy between 1998 and 2002. In-hospital mortality, complications,
      and length of stay (LOS) in hospital were compared between patients grouped by
      race. Hospitals were categorized into tertiles by the average number of radical
      cystectomies performed per year (1-4 radical cystectomies, 5-10 radical
      cystectomies, and >10 radical cystectomies). Univariate and multivariate analyses
      were performed to determine predictors of mortality, complications, LOS, and the
      likelihood that patients would undergo cystectomy at a high/medium-volume
      hospital. RESULTS: African Americans had the highest in-patient mortality,
      complications, and LOS after radical cystectomy. They also were the least likely
      to undergo radical cystectomy at a high/medium-volume hospital. When the analyses
      were controlled for potential confounding factors, there was no difference in in
      hospital mortality by race, but differences persisted in the other 3 outcome
      variables. African Americans had higher odds of complications (odds ratio [OR],
      1.57; P = .001), longer LOS (25%; P = .001), and lower odds of undergoing
      cystectomy at a high/medium-volume hospital (OR, 0.74; P = .03) compared with
      Caucasians. CONCLUSIONS: Race was an important factor in determining outcomes
      after radical cystectomy for bladder cancer. African Americans were less likely
      to undergo cystectomy at a high-volume hospital, thereby placing them at a higher
      risk of postoperative complications which ultimately may affect their survival.

PMID- 17200962
TI  - Phase II trial of dose-dense doxorubicin plus gemcitabine followed by paclitaxel
      plus carboplatin in patients with advanced urothelial carcinoma and impaired
      renal function.
AB  - BACKGROUND: Cisplatin-based therapy is standard in patients with advanced
      urothelial carcinoma but a large proportion are ineligible due to renal
      impairment. The safety and activity of a dose-dense carboplatin-based regimen in
      this patient population were explored. METHODS: Patients with advanced urothelial
      carcinoma who were ineligible for cisplatin were eligible based on at least 1 of
      the following: 1) serum creatinine >1.5 mg/dL; 2) creatinine clearance of >30
      mL/min/1.73 m(2) and <60 mL/min/1.73 m(2); and/or 3) prior nephrectomy. Patients
      received treatment with doxorubicin plus gemcitabine every other week x 5 cycles
      followed by paclitaxel plus carboplatin weekly x 12 cycles. RESULTS: Twenty-five
      patients were treated. Myelosuppression was the major toxicity, with 28% of
      patients experiencing grade 3-4 neutropenia; there were only 2 (8%) episodes of
      febrile neutropenia. Grade > or = 3 nonhematologic toxicities were infrequent
      with the exception of grade > or = 3 thrombotic episodes in 4 (16%) patients.
      There were 5 complete responses and 9 partial responses for an overall response
      rate of 56% (95% confidence interval [CI]: 35%-76%). The median survival was 15
      months (95% CI: 11-30). At a median follow-up for survivors of 45 months, 7 (28%)
      patients are disease-free. CONCLUSIONS: Dose-dense sequential chemotherapy is
      tolerable and active in patients with urothelial carcinoma and renal impairment.
      Prolonged disease-free survival is achievable in a subset of patients with
      primary unresectable disease or lymph-node only metastases treated with
      carboplatin-based therapy +/- surgical consolidation. Randomized trials are
      needed to define the optimal regimen in patients with advanced urothelial
      carcinoma and renal impairment.

PMID- 17200963
TI  - Chemotherapy for metastatic melanoma: time for a change?
AB  - Melanoma is a neoplasm with a rising incidence. Early-stage melanoma is curable,
      but advanced, metastatic melanoma almost uniformly is fatal, and patients with
      such advanced disease have a short median survival. Systemic therapy remains
      unsatisfactory, inducing complete durable responses in a small minority of
      patients. For the current review, the authors focused on the current role of
      cytotoxic chemotherapy in the treatment of metastatic melanoma and the future
      prospects for improvements for multiagent chemotherapy and chemotherapy combined
      with immunomodulatory and/or molecularly targeted agents. They discuss roles of
      single-agent chemotherapy, combination chemotherapy, combinations of chemotherapy
      with immunomodulatory or hormone agents, biochemotherapy, and combination
      chemotherapy with targeted therapies.

PMID- 17200964
TI  - Provider roles in the recruitment of underrepresented populations to cancer
      clinical trials.
AB  - BACKGROUND: Providers play a vital role in the successful recruitment of
      underrepresented patients to cancer clinical trials because they often introduce
      the opportunity of clinical trials. The purpose of the current systematic review
      was to describe provider-related factors influencing recruitment of
      underrepresented populations to cancer clinical trials. METHODS: To find original
      studies on the recruitment of underrepresented populations to cancer clinical
      trials, electronic databases from January 1966 to December 2005 were searched;
      hand-searched titles in 34 journals from January 2003 to January 2006; and
      reference lists were examined of eligible articles. Title and abstract reviews
      were conducted to identify relevant studies. Potential articles were then
      abstracted using a structured instrument and a serial review process by 2
      investigators. RESULTS: Eighteen studies were eligible for review: 13 targeted
      healthcare providers, 3 targeted patients/participants, and 2 targeted both
      providers and patients. The study designs included randomized controlled trial,
      concurrent controlled trial, case-control, descriptive, and qualitative. A lack
      of available protocols and/or a lack of provider awareness about clinical trials
      prevented providers from discussing the opportunity of clinical trials in 2
      studies. In 14 studies, patient accrual was affected by provider attitudinal
      barriers relating to patient adherence to the study protocol, patient mistrust of
      research, patient costs, data collection costs, and/or patient eligibility.
      Providers' communication methods were barriers in 5 studies and promoters in 1
      study. CONCLUSIONS: A heterogeneous body of evidence suggests that several
      provider-related factors influence recruitment of underrepresented groups to
      clinical trials. Future recruitment efforts should address these factors.

PMID- 17200965
TI  - Calcium, dietary, and lifestyle factors in the prevention of colorectal adenomas.
AB  - BACKGROUND: Many studies have suggested a role for calcium in reducing the risk
      of colorectal adenomas and cancer but its effectiveness may be dependent on
      interactions with other dietary and/or lifestyle factors. We examined the
      association between calcium and prevalence of adenomas and assessed whether the
      association was stronger in biologically plausible subgroups. METHODS: Cross
      sectional data from 222 cases and 479 adenoma-free controls who underwent
      colonoscopies and completed food frequency and lifestyle questionnaires were used
      in the analyses. Multivariable logistic regression was used to estimate the
      association between calcium and prevalence of adenomas. Stratified analyses and
      the likelihood ratio test were used to examine effect modification by various
      demographic, lifestyle, and behavioral factors. RESULTS: Overall, little
      association was observed comparing total calcium intake of > or = 900 mg/day to <
      500 mg/day (adjusted odds ratio [OR] = 0.85, 95% confidence interval [CI]: 0.53
      1.37). However, stronger associations were observed in patients with lower fat
      intake and in those who regularly (> or = 15 times/month) took nonsteroidal
      antiinflammatory drugs (NSAIDs). Specifically, total calcium intake of > or = 900
      mg/day was associated with a lower prevalence of adenomas among patients with
      lower fat intake (OR = 0.47, 95% CI: 0.25-0.91) but not among those with higher
      fat intake (OR = 1.20, 95% CI: 0.61-2.35; P-value for interaction = .01). For
      NSAIDs, the associations were OR = 0.37 (95% CI: 0.16-0.86) for regular NSAID
      users and OR = 1.27 (95% CI: 0.73-2.22) with infrequent or nonuse of NSAIDs,
      respectively (P = .06). CONCLUSIONS: The data suggest that a lower-fat diet and
      regular NSAID use may enhance calcium's effectiveness as a colorectal cancer
      preventive agent.

PMID- 17200966
TI  - Alpha,omega-functionalized 2,4-dimethylpentane dyads and 2,4,6-trimethylheptane
      triads through asymmetric hydrogenation.

PMID- 17200967
TI  - Carbene chemistry: stereoregular polymers from diazo compounds.

PMID- 17200968
TI  - The structures and optical spectra of hydrated transplutonium ions in the solid
      state and in solution.

PMID- 17200969
TI  - Modulation of characteristics of a ruthenium-coordinated flavin analogue that
      shows an unusual coordination mode.

PMID- 17200970
TI  - Triphenylamine-dendronized pure red iridium phosphors with superior OLED
      efficiency/color purity trade-offs.

PMID- 17200971
TI  - All-carbon quaternary stereogenic centers by enantioselective cu-catalyzed
      conjugate additions promoted by a chiral N-heterocyclic carbene.

PMID- 17200972
TI  - Differential fragmentation patterns of pectin oligogalacturonides observed by
      nanoelectrospray quadrupole ion-trap mass spectrometry using automated spectra
      interpretation.
AB  - Oligogalacturonides of different degrees of polymerization (DP) and methyl
      esterification (DE) were structurally analyzed by nanoESI quadrupole ion-trap
      mass spectrometry. The fragmentation patterns of the oligogalacturonides were
      compared using the program 'Virtual Expert Mass Spectrometrist' (VEMS) for
      structural annotation. In the analyzed oligogalacturonides of lower DP, the
      generation of C/Y ions, i.e. ions retaining the glycosidic oxygen, was higher
      than that of B/Z ions. In general, with oligogalacturonides of higher DP, the B/Z
      ions were generated more abundantly. Oligogalacturonides with free carboxylic
      acid groups underwent higher water loss compared to fully methyl-esterified
      oligogalacturonides under the same fragmentation conditions. Cross-ring cleavage,
      in which fragmentation occurs across the ring system of the galacturonate residue
      and signified by unique mass losses, was observed to be higher in fully methyl
      esterified oligogalacturonides than in non-methyl-esterified ones. This study
      demonstrates the different fragmentation patterns of oligogalacturonides as
      influenced by the presence or absence of methyl ester groups. For a detailed
      analysis of unknown oligogalacturonides, cross-ring fragmentation gives more
      structural information than glycosidic bond cleavage. One implication of this is
      that more structural information is obtained when analyzing methyl-esterified
      oligogalacturonides than non-methyl-esterified ones in an ion-trap instrument.
      This is of particular importance in pectin chemistry, where mass spectrometry has
      become the technique of choice for structural determination. Although this study
      was not designed to explain the mechanisms of oligogalacturonide fragmentation,
      possible explanations for why non-methyl-esterified oligogalacturonides undergo
      more water loss than methyl-esterified ones will be postulated. In addition, the
      VEMS program was extended to automatically interpret and assign the fragment ions
      peaks generated in this study.

PMID- 17200973
TI  - Determination of roxatidine in human plasma by liquid chromatography/electrospray
      mass spectrometry and application to a clinical pharmacokinetic study.
AB  - A rapid and sensitive liquid chromatography/mass spectrometry (LC/MS) method was
      developed and validated for the determination of roxatidine in human plasma.
      Roxatidine was extracted by single liquid-liquid extraction with tert-butyl
      methyl ether, and the chromatographic separation was performed on a C8 column.
      The total analytical run time was relatively short (5 min), and the limit of
      assay quantification was 2 ng/mL using 0.1 mL of human plasma. Roxatidine and the
      internal standard, propranolol, were monitored in selected ion monitoring (SIM)
      mode at m/z 307.3 and 260.3, respectively. The standard curve was linear over a
      concentration range from 2-500 ng/mL, and the correlation coefficients were
      >0.999. The mean intra- and inter-day assay accuracy ranged from 103.4-108.8% and
      102.3-110.0%, respectively, and the mean intra- and inter-day precision was
      between 3.3-8.8% and 5.3-6.2%, respectively. The developed assay method was
      successfully applied to a pharmacokinetic study in human volunteers after oral
      administration of roxatidine acetate hydrochloride at a dose of 75 mg.

PMID- 17200974
TI  - Increasing the sensitivity of delta13C and delta15N abundance measurements by a
      high sensitivity elemental analyzer connected to an isotope ratio mass
      spectrometer.
AB  - A common elemental analyzer system connected to a temperature-controlled gas
      chromatography (GC) column and coupled to an isotope ratio mass spectrometer was
      improved to decrease the determination limit for a simultaneous stable isotope
      ratio measurement of nitrogen and carbon dioxide. The additional use of a special
      ashtray system to collect the combustion residuals permitted more time-efficient
      work. These modifications to the elemental analyzer allowed precise measurements
      to be made down to 1.5 microg nitrogen and 10 microg carbon for stable isotope
      analysis. Low system background values and an acceptable signal-to-noise ratio
      have made an additional blank correction for these low sample measurements
      unnecessary. We provide a precision of this stable isotope analysis for lowest
      amounts of 1.2-2 microg nitrogen with a standard deviation of +/-0.496 per
      thousand (n = 27) and for 8.2-15 microg carbon with a standard deviation of +/
      0.257 per thousand (n = 31) across different sample runs under stipulated
      conditions. This application can be established in an automatic mode without
      cryofocusing procedures.

PMID- 17200975
TI  - Rapid identification of C21 steroidal saponins in Cynanchum versicolor Bunge by
      electrospray ionization multi-stage tandem mass spectrometry and liquid
      chromatography/tandem mass spectrometry.
AB  - Electrospray ionization multi-stage tandem mass spectrometry (ESI-MSn) and liquid
      chromatography coupled with on-line electrospray ionization tandem mass
      spectrometry (LC/ESI-MSn) were performed to elucidate the clearage rule of nine
      investigated C21 steroidal saponins and identify them in the saponin fraction of
      90% ethanolic extracts from the root and rhizome of Cynanchum versicolor Bunge.
      The fragments of C21 steroidal saponins in positive and negative ESI-MSn were
      used to deduce their mass spectral fragmentation mechanisms, and their structures
      were further confirmed by ESI-MSn in positive mode. The MSn spectra of the
      [M+Na]+ ions for saponins provided a wealth of structural information on
      glycosidic bond cleavage, which allowed a straightforward interpretation of
      spectra, with respect to the identifications of features such as the sequences of
      sugars attached to saponins and sugar type. By using LC/ESI-MSn, nine C21
      steroidal saponins were detected in the saponin fraction of C. versicolor, and an
      isomer of atratoglaucoside A was elucidated simultaneously. All nine compounds
      showed an abundant ion for the loss of 46 Da (HCOOH) from [M+Na]+. The losses of
      monosaccharide sequences and aglycone as neutral fragmentation from [M+Na-HCOOH]+
      were also acquired as the characteristic ions of these C21 steroidal saponins. It
      provided important information on monosaccharide sequences and in particular on
      sugar types and could be used to identify and elucidate other C21 steroidal
      saponins. These studies allowed us to rapidly identify C21 steroidal saponins
      from Radix cynanchi atrati. It is indicated that the described method had wide
      applicability to rapidly screen and provide structural confirmation on C21
      steroidal saponins in crude materials.

PMID- 17200976
TI  - Secondary metabolism of olive secoiridoids. New microcomponents detected in
      drupes by electrospray ionization and high-resolution tandem mass spectrometry.
AB  - Olive drupe tissues have been selected as a possible source of information about
      the secondary metabolism of oleaceae secoiridoids. The structures of a number of
      new microcomponents, detected and isolated by a combined high-performance liquid
      chromatography (HPLC)-fraction collector/ultraviolet electrospray ionization mass
      spectrometry (UV/ESI-MS) apparatus, can be inferred from the data obtained by
      high-resolution tandem mass spectrometry in a QqTOF instrument. Some of them (1,
      2, 3 and 4) are closely correlated to oleuropein. Others, such as neo-nuzhenide
      (5) and 2''-hydroxyoleuropein (6), typical of other oleaceae families, have never
      been found in olive tissues.

PMID- 17200977
TI  - Immuno-mass spectrometry assay of EPI-HNE4, a recombinant protein inhibitor of
      human elastase.
AB  - In order to increase the sensitivity of liquid chromatography/mass spectrometry
      (LC/MS) assays of recombinant proteins for pharmacokinetics studies, we have
      developed an immuno-mass spectrometry assay for EPI-hNE4, a 6237 Da protein
      currently developed for respiratory distress syndromes. After immunocapture of
      the analyte in human plasma with magnetic beads coated with anti-EPI-hNE4
      antibodies, the intact protein was eluted and separated in reversed-phase LC and
      then analysed by tandem mass spectrometry (MS/MS) in selected reaction monitoring
      (SRM) mode. The problem of analytical interference due to endogenous binding
      antibodies was addressed by successive steps of acidification and neutralisation
      before immunocapture. Furthermore, potential variations in the recovery of
      analyte during sample extraction were compensated for by addition of an internal
      standard recognised by the antibodies. The precision of the assay remained
      therefore below 15%. A significant increase in assay sensitivity was achieved
      since the extraction step allowed sample concentration and removal of matrix
      components interfering with the electrospray ionisation process. Using 0.4 mL of
      plasma, a limit of quantification at 0.5 ng/mL (80 pM) was reached, which
      represents a 10-fold improvement in sensitivity over our previous work using
      sample precipitation. This technique was able to monitor EPI-hNE4 kinetics in the
      plasma of human subjects for 36 h after an intravenous administration of 0.125
      mg/kg.

PMID- 17200978
TI  - Mass spectrometric detection of CP4 EPSPS in genetically modified soya and maize.
AB  - The potential of protein fractionation hyphenated to mass spectrometry (MS) to
      detect and characterize the transgenic protein present in Roundup Ready soya and
      maize has been investigated. Genetically modified (GM) soya and maize contain the
      5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene from Agrobacterium
      tumefaciens CP4, which confers resistance to the herbicide glyphosate. The GM
      soya and maize proteomes were fractionated by gel filtration, anion-exchange
      chromatography and sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS
      PAGE) prior to MS. This facilitated detection of a tryptic peptide map of CP4
      EPSPS by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF)
      MS and nanoelectrospray ionization quadrupole time-of-flight (nanoESI-QTOF) MS.
      Subsequently, sequence information from the CP4 EPSPS tryptic peptides was
      obtained by nanoESI-QTOF MS/MS. The identification was accomplished in 0.9% GM
      soya seeds, which is the current EU threshold for food-labeling requirements.

PMID- 17200979
TI  - Recommended criteria for the mass spectrometric identification of target peptides
      and proteins (<8 kDa) in sports drug testing.
AB  - Mass spectrometry has become an invaluable tool for the identification of
      prohibited peptide hormones and proteins in doping control analysis. Regulatory
      authorities have established criteria for identifying banned drugs in doping
      control specimens, but these criteria do not address the specific issues for high
      molecular weight protein drugs such as molecular weight determination of multiply
      charged molecules, analysis of chemically or enzymatically derived degradation
      products, identification of amino acid sequence tags, etc. Technical
      considerations such as sample preparation methods (e.g. immunoaffinity
      purification), resulting analytes (e.g. intact compounds vs. chemically or
      enzymatically derived peptides), ionization modes, analyzer resolution, and the
      information provided by respective techniques are discussed in light of sports
      drug testing requirements using typical application examples.

PMID- 17200982
TI  - Double cation adduction in matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry of electron deficient anthraquinone derivatives.
AB  - Six anthraquinone derivatives were analyzed using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS). Clear
      (pseudo) molecular ions were observed for all the compounds. Interestingly, for
      some derivatives, strong ions with double cation adduction were also recorded in
      the positive mode. It is remarkable that all these ions are singly charged. In
      this work, possible mechanisms for the double cation adduction were investigated
      and discussed. It appears that the double cation adduction was due to the
      electron deficient nature of the derivatives, and formed by taking up two singly
      charged cations and one electron. Substituents on the anthraquinone ring were
      found to have a significant effect on the double cation adduction. In contrast,
      no considerable influence of the acidity of MALDI matrix/solution was observed,
      even on the double proton adduction. Furthermore, it was demonstrated that double
      cation adduction might occur in the MALDI gas-phase plume. In addition to the
      anthraquinones, three more electron deficient compounds of different types, i.e.
      a perylene bisimide derivative (PB), 3,7-decanoylamino-4,8-dihydrobenzo[1,2-b:4,5
      b']dithiophene-4,8-dione (TQ) and 6,6-phenyl C61-butyric acid methyl ester
      (PCBM), were also analyzed with MALDI TOF MS. The results indicate that the
      'abnormal' double cation adduction might be a 'normal' phenomenon in the MALDI
      TOF MS analysis of many electron deficient compounds.

PMID- 17200983
TI  - 16th World Congress on Ultrasound in Obstetrics and Gynecology, 3-7 September
      2006, London, UK: presentations and awards.

PMID- 17200981
TI  - The role of MDR-related proteins in the prognosis of adult acute myeloid
      leukaemia (AML) with normal karyotype.
AB  - Cytogenetic abnormalities are among the most important factors affecting the
      outcome of patients with acute myeloid leukaemia (AML), but approximately 40-50%
      of AML cases display a normal karyotype at diagnosis. Multidrug resistance (MDR)
      proteins overexpression is associated with worse prognosis in acute leukaemias,
      but its role in normal karyotype AML is less defined. We analysed the expression
      of P-glycoprotein (PGP), MDR-related protein (MRP) and lung resistance protein
      (LRP) in 135 adult patients with normal karyotype AML and its correlation with
      other biological features of the disease, to evaluate the impact of MDR proteins
      on response to therapy and on survival. Increased PGP expression was associated
      with lower rate of complete remission (CR; p = 0.006), similarly to advanced age.
      Cases overexpressing PGP displayed also a shorter event-free survival (EFS; 4 vs.
      10 months, p = 0.035) and the increased expression of at least one MDR protein
      was associated with a reduced overall survival (OS; p = 0.038). Also age was
      predictive of worse prognosis. Our data confirm the prognostic role of MDR
      proteins, in particular of PGP, also in AML patients with normal karyotype at
      diagnosis. This finding could be used to stratify patients with different
      prognosis and to design risk-adapted therapeutic strategies.

PMID- 17200980
TI  - Intramolecular interchain reactions in bidesmosidic glycosides, a new insight
      into carbohydrate rearrangements induced by electrospray ionisation.
AB  - Glycoconjugates are a class of complex molecules that are widely distributed in
      the plant kingdom and in some marine organisms. This class of compounds has a
      wide range of biological activities such as anti-inflammatory, antimicrobial,
      antifungal, anticancer, antiulcer, and immunoenhancing actions.1-3 Some of them
      also show various toxic activities such as cytotoxic, hemolytic, cardiotoxic, and
      teratogenic. Among these compounds, steroidal and triterpenoid saponins have long
      been known as components of widely used herbal drugs and pharmaceutical
      preparations; ginseng, Tribulus terrestris, Quillaja saponaria, and Digitalis
      ssp. are just a few examples. Thus, identification of saponins in herbal drugs
      used worldwide is of significance in phytochemical and toxicological quality
      control studies, and for the production of safe health products. Therefore, there
      is continuing demand for methods to rapidly identify and characterize these
      natural products.

PMID- 17200984
TI  - Protective effects of N-acetyl-L-cysteine against acute carbon tetrachloride
      hepatotoxicity in rats.
AB  - In recent years, N-acetyl-L-cysteine (NAC) has been widely investigated as a
      potentially useful protective and antioxidative agent to be applied in many
      pathological states. The aim of the present work was further evaluation of the
      mechanisms of the NAC protective effect under carbon tetrachloride-induced acute
      liver injuries in rats. The rat treatment with CCl4 (4 g/kg, intragastrically)
      caused pronounced hepatolysis observed as an increase in blood plasma bilirubin
      levels and hepatic enzyme activities, which agreed with numerous previous
      observations. The rat intoxication was accompanied by an enhancement of membrane
      lipid peroxidation (1.4-fold) and protein oxidative damage (protein carbonyl
      group and mixed protein-glutathione disulphide formations) in the rat liver. The
      levels of nitric oxide in blood plasma and liver tissue significantly increased
      (5.3- and 1.5-fold, respectively) as blood plasma triacylglycerols decreased (1.6
      fold). The NAC administration to control and intoxicated animals (three times at
      doses of 150 mg/kg) elevated low-molecular-weight thiols in the liver. The NAC
      administration under CCl4-induced intoxication prevented oxidative damage of
      liver cells, decreased membrane lipid peroxidation, protein carbonyls and mixed
      protein-glutathione disulphides formation, and partially normalized plasma
      triacylglycerols. At the same time the NAC treatment of intoxicated animals did
      not produce a marked decrease of the elevated levels of blood plasma ALT and AST
      activities and bilirubin. The in vitro exposure of human red blood cells to NAC
      increased the cellular low-molecular-weight thiol levels and retarded tert
      butylhydroperoxide-induced cellular thiol depletion and membrane lipid
      peroxidation as well as effectively inhibited hypochlorous acid-induced
      erythrocyte lysis. Thus, NAC can replenish non-protein cellular thiols and
      protect membrane lipids and proteins due to its direct radical-scavenging
      properties, but it did not attenuate hepatotoxicity in the acute rat CCl4
      intoxication model.

PMID- 17200985
TI  - Effect of oral vitamin E supplementation on oxidative stress in guinea-pigs with
      short-term hypothermia.
AB  - Effects of oral vitamin E supplementation on blood malondialdehyde (MDA),
      glutathione (GSH) and vitamin E levels and superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px) enzyme activities in acute hypothermia of guinea
      pigs were investigated. Thirty male guinea pigs, weighing 500-800 g were randomly
      divided into one of three experimental groups: A (control, without cooling), B
      (hypothermic) and C (hypothermic with vitamin E supplementation). The guinea-pigs
      of group C received daily oral supplementation of 460 mg kg(-1) bw vitamin E for
      4 days before inducing hypothermia. Twenty-four hours after the last vitamin E
      supplementation, the guinea-pigs of the B and C groups were cooled by immersion
      into cold water (10-12 degrees C), and the control guinea-pigs were immersed into
      water of body temperature (37 degrees C) up to the neck for 5 min without using
      any anaesthetic or tranquilizer. Rectal body temperatures of groups were measured
      and blood samples for biochemical analysis were collected immediately after the
      cooling. The body temperature, GSH and vitamin E levels and GSH-Px enzyme
      activity of hypothermic guinea-pigs were lower (p < 0.05), but SOD enzyme
      activity was not different (p > 0.05) from those of control animals. Although,
      the body temperature of hypothermic with vitamin E supplementation group was
      lower (p < 0.05), all other parameters of this group were not different (p >
      0.05) from the controls. It was concluded that oral supplementation of vitamin E
      can alleviate the lipid peroxidation-induced disturbances associated with
      hypothermia by increasing the serum vitamin E level to normal. However, more
      studies are needed to prove whether this vitamin can improve quality of life
      during the cold seasons.

PMID- 17200987
TI  - Fetal imaging: a brief history of the future.

PMID- 17200986
TI  - Interpretation of interleukin-2 receptor alpha positive cells during induction
      chemotherapy for adult acute myelogenous leukaemia patients.
AB  - To correlate clinical outcomes with the expression of interleukin-2 receptor
      alpha (CD25) positive cells during induction chemotherapy (IC) in adult patients
      with acute myeloid leukaemia (AML), we investigated the prognostic importance of
      subsets of peripheral blood (PB) CD45+CD25+ cells. Seventy-five patients with
      newly diagnosed AML received the same initial IC; and serial PB samples were
      taken. The gated CD45/CD25 cell populations were used to compare the intensity of
      immunophenotypic signals based on the treatment timeline. Patients who responded
      poorly to IC demonstrated exceptionally higher levels of PB CD45+CD25+ cells by
      percentage (p = 0.003) or by absolute count (p = 0.046) on the seventh day (D +
      7) of initial IC. In addition, patients in complete remission (CR) (n = 61)
      demonstrated relatively lower levels of steady PB CD45+CD25+ after standard IC.
      These results suggest that the expression of CD25 can be used to predict the
      response to IC during an early period of treatment.

PMID- 17200988
TI  - 3D and 4D ultrasound in fetal cardiac scanning: a new look at the fetal heart.
AB  - Over the last decade we have been witness to a burgeoning literature on three
      dimensional (3D) and four-dimensional (4D) ultrasound-based studies of the fetal
      cardiovascular system. Recent advances in the technology of 3D/4D ultrasound
      systems allow almost real-time 3D/4D fetal heart scans. It appears that 3D/4D
      ultrasound in fetal echocardiography may make a significant contribution to
      interdisciplinary management team consultation, health delivery systems, parental
      counseling, and professional training. Our aim is to review the state of the art
      in 3D/4D fetal echocardiography through the literature and index cases of normal
      and anomalous fetal hearts.

PMID- 17200989
TI  - Statistical methods for constructing gestational age-related reference intervals
      and centile charts for fetal size.

PMID- 17200990
TI  - Maternal cardiac function in fetal growth-restricted and non-growth-restricted
      small-for-gestational age pregnancies.
AB  - OBJECTIVE: To compare maternal cardiac function in women with intrauterine growth
      restriction (IUGR) to those with small-for-gestational age (SGA) pregnancies (non
      IUGR). METHODS: This was a cross-sectional study involving maternal
      echocardiography and uterine, umbilical and fetal middle cerebral artery Doppler
      assessment in 52 normotensive women at 20-36 weeks' gestation with SGA fetuses
      (26 IUGR and 26 non-IUGR). RESULTS: In the IUGR (compared to the non-IUGR) group,
      maternal cardiac output (CO) was lower (4.7 vs. 6.1 L/min, P<0.001) and total
      vascular resistance (TVR) was higher (1444 vs. 1088 dynes/s/cm5, P<0.001). The
      lower CO was due to a lower preload, demonstrated by a reduced stroke volume
      (59.9 vs. 73.6 mL, P<0.01) and smaller left atrial diameter (LAD) (31.5 vs. 34.1
      mm, P=0.01). Mean arterial pressure and diastolic function were similar between
      the groups. Logistic regression and receiver-operating characteristics curve
      analysis for detection of IUGR demonstrated that a model using TVR, LAD, fetal
      middle cerebral artery pulsatility index and gestational age, had a sensitivity
      of 96.2% and a specificity of 84.6%. CONCLUSIONS: Maternal echocardiography can
      provide a very sensitive tool for identifying IUGR pregnancies.

PMID- 17200992
TI  - Sonographic examination of the fetal central nervous system: guidelines for
      performing the 'basic examination' and the 'fetal neurosonogram'.

PMID- 17200993
TI  - Immediate and long-term outcomes in children with prenatal diagnosis of selected
      isolated congenital heart defects.
AB  - OBJECTIVES: To compare the immediate postinterventional and long-term outcomes of
      children with a prenatal and those with a postnatal diagnosis of isolated
      congenital heart defects. METHODS: This was a retrospective study of 257 children
      admitted over a 10-year period to our pediatric cardiology unit with one of four
      different cardiac lesions: transposition of the great arteries, atrioventricular
      canal defect, tetralogy of Fallot and pulmonary atresia; 208 were diagnosed
      postnatally and 49 prenatally. Management was identical in the two patient
      groups. RESULTS: The median age at admission was 22 days in the postnatal group
      and 10 days in the prenatal group. In the prenatal group there was a higher
      median preoperative O2 saturation level (P=0.07), fewer cases of preoperative
      cardiac failure (P=0.03), fewer cases of preoperative closure of the duct
      (P=0.04), a shorter median duration of postoperative mechanical ventilation
      (P=0.03), less need for resurgery (P=0.02) and a shorter median duration of stay
      in the intensive care unit (P=0.05). Postoperative survival was 96% in the
      prenatal group and 90% in the postnatal group. Assessment of long-term survival
      revealed a longer catheter intervention-free interval in the prenatal group
      (P=0.03). At the 1-year follow-up, residual impaired cardiac function was less
      frequent in the prenatal than in the postnatal group (P=0.04). Overall survival
      at maximum follow-up was 92% in the prenatal and 84% in the postnatal group.
      CONCLUSIONS: Prenatal diagnosis of isolated congenital heart defects allows
      admission for surgery in a more stable condition and is associated with lower
      short-term and long-term morbidity and mortality.

PMID- 17200995
TI  - Fetuses with features of first-trimester peritonitis and a favorable outcome.

PMID- 17200994
TI  - Trends in antidepressant overdoses.
AB  - BACKGROUND: Debate continues about antidepressants and suicide. However, there
      are few recent nation-wide data about antidepressant overdoses. The purpose of
      this study was to describe United States trends from 1983 through 2003 in
      antidepressant overdoses as well as trends in health care utilization and
      mortality. METHODS: Data were obtained from the American Association of Poison
      Control Centers' (AAPPC) Toxic Exposure Surveillance System (TESS), the National
      Hospital Ambulatory Medical Care Survey (NHAMCS) of emergency departments, and
      the National Hospital Discharge Survey(NHDS). RESULTS: Antidepressant overdose
      reports rose dramatically in the United States (from 0.61 per 10,000 population
      in 1983 to 3.26 per 10,000 population in 2003) chiefly due to the rise in
      selective serotonin reuptake inhibitor (SSRI) ingestion. However, fatalities per
      antidepressant overdose report declined from 73 per 10,000 reported ingestions to
      32 per 10,000 ingestions. Tricyclic antidepressant (TCA) overdoses had higher
      rates of hospitalization (78.7 vs. 64.7% hospitalized) and much higher fatality
      rates than did SSRI overdose reports (0.73 vs. 0.14% mortality). If the 55,977
      SSRI overdoses in 2003 had represented TCA overdoses, then (other things being
      equal) approximately 410 fatalities would have been expected but only 106 people
      died. Emergency department visits associated with antidepressant overdose
      increased along with all emergency department visits. Hospitalization associated
      with antidepressant overdose increased in the early 1980s but then reached a
      plateau while overall hospitalizations declined. CONCLUSIONS: The dramatic rise
      in United States antidepressant overdoses has not been reflected in
      antidepressant overdose fatalities nor in hospitalizations. If the marked
      increase in antidepressant overdoses in the United States had involved TCAs
      rather than SSRIs, then there would have been roughly 300 excess deaths annually.

PMID- 17200997
TI  - Solution structure of domain 6 from a self-splicing group II intron ribozyme: a
      Mg(2+) binding site is located close to the stacked branch adenosine.
AB  - Group II intron self-splicing is essential for the correct expression of
      organellar genes in plants, fungi, and yeast, as well as of bacterial genes. Self
      excision of these autocatalytic introns from the primary RNA transcript is
      achieved in a two-step mechanism that is apparently analogous to that of the
      eukaryotic spliceosome. The 2'-OH of a conserved adenosine (the branch point)
      located within domain 6 (D6) acts as the nucleophile in the first step of
      splicing. Despite the biological importance of group II introns, little is known
      about their structural organization and usage of metal ions in catalysis. Here we
      report the first solution structure of a catalytically active D6 construct
      encompassing the branch point and the neighboring helical regions from the
      mitochondrial yeast intron ai5gamma. The branch adenosine is the single unpaired
      nucleotide, and, in contrast to the spliceosomal branch site, resides within the
      helix, being partially stacked between two flanking GU wobble pairs. We
      identified a novel prominent Mg(2+) binding site in the major groove of the
      branch site. Importantly, Mg(2+) addition does not impair the stacking of the
      branch adenosine, rather it strengthens the interaction with the flanking
      uridines, as shown by NMR and fluorescence studies. This means that domain 6
      presents the branch adenosine in a stacked fashion to the core of group II
      introns upon folding to the active conformation.

PMID- 17200996
TI  - Observation of an unusually facile fragmentation pathway of gas-phase peptide
      ions: a study on the gas-phase fragmentation mechanism and energetics of tryptic
      peptides modified with 4-sulfophenyl isothiocyanate (SPITC) and 4
      chlorosulfophenyl isocyanate (SPC) and their 18-crown-6 complexes.
AB  - Various peptide modifications have been explored recently to facilitate the
      acquisition of sequence information. N-terminal sulfonation is an interesting
      modification because it allows unambiguous de novo sequencing of peptides,
      especially in conjunction with MALDI-PSD-TOF analysis; such modified peptide ions
      undergo fragmentation at energies lower than those required conventionally for
      unmodified peptide ions. In this study, we systematically investigated the
      fragmentation mechanisms of N-terminal sulfonated peptide ions prepared using two
      different N-terminal sulfonation reagents: 4-sulfophenyl isothiocyanate (SPITC)
      and 4-chlorosulfophenyl isocyanate (SPC). Collision-induced dissociation (CID) of
      the SPC-modified peptide ions produced a set of y-series ions that were more
      evenly distributed relative to those observed for the SPITC-modified peptides;
      y(n-1) ion peaks were consistently and significantly larger than the signals of
      the other y-ions. We experimentally investigated the differences between the
      dissociation energies of the SPITC- and SPC-modified peptide ions by comparing
      the MS/MS spectra of the complexes formed between the crown ether 18-crown-6 (CE)
      and the modified peptides. Upon CID, the complexes formed between 18-crown-6
      ether and the protonated amino groups of C-terminal lysine residues underwent
      either peptide backbone fragmentation or complex dissociation. Although the crown
      ether complexes of the unmodified ([M + CE + 2H]2+) and SPC-modified ([M* + CE +
      2H]2+) peptides underwent predominantly noncovalent complex dissociation upon
      CID, the low-energy dissociations of the crown ether complexes of the SPITC
      modified peptides ([M' + CE + 2H]2+) unexpectedly resulted in peptide backbone
      fragmentations, along with a degree of complex dissociation. We performed quantum
      mechanical calculations to address the energetics of fragmentations observed for
      the modified peptides.

PMID- 17200998
TI  - The cytotoxicity of saponins correlates with their cellular internalization.

PMID- 17200999
TI  - Remote modulation of amine basicity by a phenylsulfone and a phenylthio group.

PMID- 17201000
TI  - Guest-dependent flexible coordination networks with fluorinated ligands.
AB  - Guest-dependent flexible coordination networks are formed from 1,4-bis(4
      pyridylmethyl)tetrafluorobenzene (bpf), 4,4'-bis(4
      pyridylmethyl)octafluorobiphenyl (bpfb), 2,6-bis(4
      pyridylmethyl)hexafluoronaphthalene (2,6-bpfn), and 2,7-bis(4
      pyridylmethyl)hexafluoronaphthalene (2,7-bpfn) with Cd(NO3)2 in the presence of
      various organic compounds. The reaction of bpf affords one-dimensional cyclic
      chains, two-dimensional rhombus grid sheets, and three-dimensional diamond
      frameworks with threefold interpenetration. The reaction of bpfb mainly affords
      two-dimensional rhombus grid sheets with twofold parallel interpenetration. The
      reaction of 2,6-bpfn affords a one-dimensional ladder and two-dimensional rhombus
      grid, twisted grid, and herringbone sheets. The reaction of 2,7-bpfn affords two
      dimensional rhombus grid sheets and grid sheets with dumbbell-shaped cavities.
      This diversity of network topologies is induced by interactions between the guest
      molecules and the flexible ligand frameworks.

PMID- 17201001
TI  - Dissecting the general physicochemical properties of noncovalent interactions
      involving tyrosine side chain as a second-shell ligand in biomolecular metal
      binding site mimetics: an experimental study combining fluorescence, 13C NMR
      spectroscopy and ESI mass spectrometry.
AB  - Detailed physicochemical features inherent in the dynamic cation-pi interactions
      of aromatic amino acid side chains in the secondary coordination spheres around
      metal ions were extracted and mapped by intrinsic tyrosine fluorescence titration
      experiments with two homologous, artificially engineered metal-binding scaffolds
      which mimic metal-binding sites in metalloproteins. A newly formulated method for
      the treatment of fluorescence titration data allows straightforward assessment of
      both the magnitudes and properties of metal-chelation-assisted cation-aromatic
      interactions (K2) underlying a proposed two-step metallosupramolecular
      association process. The unprecedented linear platform-motif correlations between
      the two contrasting scaffolds in their changes in tyrosine fluorescence on
      binding of 3d metal cations help to elucidate the properties of general cation
      arene recognition corresponding to the metal-responsive characteristics of the
      second-shell Tyr residue surrounding the metal-binding sites in the
      supramolecular context, and thereby define a new noncovalent design principle for
      metal-ion recognition in aqueous solution. As supported by NMR spectroscopic and
      ESI-MS analyses and molecular mechanics force field calculations, the systematic
      study exemplifies the concept of using steady-state tyrosine fluorescence as a
      powerful tool for comprehensive descriptions of cation-pi interactions in the
      extended environment of a metal-binding site. We established that the
      physicochemical properties pertaining to indirect metal-arene interactions are
      highly dependent on the electronic properties of the metal ions. This work
      suggests that second-shell cation-pi interactions may play more diverse roles,
      including modulation of structure, reactivity, and function of metal-binding
      sites, than the previously well-established direct cation-pi interactions
      involving hard cations (e.g., alkali metal ions). Moreover, such a study will
      continue to complement theoretical predications and/or the early experimental
      investigations in organic solvents.

PMID- 17201002
TI  - Influence of helical twisting power on the photoswitching behavior of chiral
      azobenzene compounds: applications to high-performance switching devices.
AB  - Five photochromic chiral azobenzene compounds and one nonphotochromic chiral
      compound were synthesized and characterized by IR, 1H NMR spectroscopy, and
      elemental analysis. Cholesteric liquid crystalline phases were induced by mixing
      of the nonphotochromic chiral compound and one of the photochromic chiral
      azobenzene compounds in a host nematic liquid crystal (E44). The helical pitch of
      the induced cholesteric phase was determined by Cano's wedge method and the
      helical twisting power (HTP) of each sample was thus determined. The helical
      twisting powers of azobenzene compounds were decreased upon UV irradiation, due
      to trans-->cis photoisomerization of azobenzene molecules. Among the azobenzene
      compounds synthesized in our study, Azo-5, with isomannide (radical) as chiral
      photochromic dopant, showed the highest HTP and contrast ratio (Tmax/Tmin).
      Photoswitching between compensated nematic phase and cholesteric phase was
      achieved through reversible trans<-->cis photoisomerization of the chiral
      azobenzene molecules through irradiation with UV and visible light, respectively.
      Transmission rates (contrast ratios) increased with decreasing helical pitch
      length in the induced cholesteric phase. The influence of helical twisting power
      on the photoswitching behavior of chiral azobenzene compounds is discussed in
      detail.

PMID- 17201003
TI  - Lamellar and three-dimensional hybrid compounds formed by cyclohexene- and
      cyclohexanedicarboxylates of Pb, La, and Cd.
AB  - To establish factors that determine the formation of three-dimensional hybrid
      structures of metal dicarboxylates involving metal-oxygen-metal linkages, we have
      investigated metal dicarboxylates derived from 1,2-cyclohexene as well as 1,2-,
      1,3-, and 1,4-cyclohexane dicarboxylic acids. Thus, we have synthesized a 1,2
      cyclohexenedicarboxylate of Cd, [Cd(1,2-CHeDC)(H2O)] (I), a 1,2
      cyclohexanedicarboxylate of Pb, [Pb(1,2-CHDC)] (II), and three 1,4
      cyclohexanedicarboxylates of La [La2(1,4-CHDC)3(H2O)4] (III), [La3(1,4
      HCHDC)2(1,4-CHDC)5(H2O)2].H2O (IV) and [La2(1,4-CHDC)3(H2O)].2.5 H2O (V) under
      hydrothermal conditions and determined their structures. A mixed dicarboxylate
      involving both 1,3- and 1,4-cyclohexenedicarboxylates of Pb, [Pb3O(1,3-CHDC)(1,4
      CHDC)].0.5 H2O (VI) and a 1,4-cyclohexanedicarboxylate of Pb, [Pb(6)O(2)(1,4
      CHDC)3(1,4-HCHDC)2], have also been synthesized and characterized. While the 1,2
      dicarboxylates have layered structures, the 1,4-dicarboxylates and the mixed
      dicarboxylates possess three-dimensional structures. Interestingly, both the 1,2
      and 1,4-dicarboxylates are true hybrid compounds composed of infinite M-O-M
      linkages. The equatorial-equatorial (e,e) conformation is adopted commonly in all
      these compounds, although less stable conformations are encountered occasionally.
      The formation of the layered and the three-dimensional structures can be
      understood based on the relative disposition of the two carboxylic groups, the
      1,4-isomer favoring the three-dimensional structure. Based on the results of the
      present study along with the available literature, we conclude that in order to
      obtain three-dimensional hybrid structures with metal-oxygen-metal networks, it
      appears necessary to make use of the 1,4-cyclohexanedicarboxylic acid.

PMID- 17201004
TI  - Investigation of the mechanism of action of pyrogallol-phloroglucinol
      transhydroxylase by using putative intermediates.
AB  - Pyrogallol-phloroglucinol transhydroxylase from Pelobacter acidigallici, a
      molybdopterin-containing enzyme, catalyzes a key reaction in the anaerobic
      degradation of aromatic compounds. In vitro, the enzymatic reaction requires
      1,2,3,5-tetrahydroxybenzene as a cocatalyst and the transhydroxylation occurs
      without exchange with hydroxy groups from water. To test our previous proposal
      that the transfer of the hydroxy group occurs via 2,4,6,3',4',5'
      hexahydroxydiphenyl ether as an intermediate, we synthesized this compound and
      investigated its properties. We also describe the synthesis and characterization
      of 3,4,5,3',4',5'-hexahydroxydiphenyl ether. Both compounds could substitute for
      the cocatalyst in vitro. This indicates that the diphenyl ethers can intrude into
      the active site and initiate the catalytic cycle. Recently, the X-ray crystal
      structure of the transhydroxylase (TH) was published16 and it supports the
      proposed mechanism of hydroxy-group transfer.

PMID- 17201006
TI  - A fluorous, Pummerer cyclative-capture strategy for the synthesis of N
      heterocycles.
AB  - A fluorous, cyclative-capture strategy based on a new Pummerer cyclization
      process allows rapid access to tagged, heterocyclic frameworks. Convenient
      modification of the fluorous, heterocyclic scaffolds by using a variety of
      approaches including Pd-catalyzed cross-couplings is possible. Traceless,
      reductive cleavage of the fluorous-phase tag or oxidative cleavage and further
      elaboration, completes a strategy for the high-throughput, fluorous-phase
      synthesis of a diverse range of N-heterocycles.

PMID- 17201005
TI  - Near-infrared absorbing ligand-oxidized dinuclear phthalocyanines.
AB  - Ligand-oxidized annulated dinuclear phthalocyanine zinc(II) and lithium(I)
      complexes absorbing in the NIR region (lambda=1000-2200 nm) with high extinction
      coefficients are described. Analogous mononuclear Pc complexes were used for
      comparison. The oxidized Pcs were characterized in solution by electronic
      absorption, EPR and NMR spectra. The NIR transitions were explained by using MO
      diagrams calculated semiempirically. The reversible oxidation behavior of the
      phthalocyanine complexes was also estimated by cyclic voltammetry. These new
      extremely long wavelength absorbing phthalocyanines are interesting as materials
      with new electronic properties.

PMID- 17201007
TI  - Feasibility of fetal cardiac magnetic resonance imaging: preliminary experience.

PMID- 17201008
TI  - Retrocecal-periappendicular abscess in pregnancy: diagnosis by ultrasound and
      magnetic resonance imaging.

PMID- 17201009
TI  - Management of a placental chorioangioma with endoscopic devascularization and
      intrauterine transfusions.

PMID- 17201010
TI  - Natural-abundance 15N--13C correlation spectra of vitamin B-12.
AB  - Two-dimensional nitrogen-carbon NMR correlation spectra have been derived by a
      new reconstruction technique based on standard two-dimensional HMQC and HMBC
      spectra, and operating with natural 15N and 13C isotopic abundances. Compared
      with conventional three-dimensional spectroscopy in which 15N and 13C spins must
      be present in the same molecule, the reconstruction method offers two orders of
      magnitude improvement in sensitivity. Vitamin B-12 serves as an illustrative
      example.

PMID- 17201012
TI  - The accuracy of first trimester ultrasound in the diagnosis of hydatidiform mole.
AB  - OBJECTIVE: Previous studies have examined ultrasound findings in
      histopathologically confirmed cases of hydatidiform mole. The aim of this study
      was to assess the first-trimester ultrasonographic findings in all women
      suspected of having hydatidiform mole on ultrasound and those subsequently
      diagnosed with hydatidiform mole after histological examination of removed
      products of conception after surgical evacuation of the uterus. The aim was to
      obtain a true sensitivity and positive predictive value for ultrasound in the
      diagnosis of hydatidiform mole. METHODS: A retrospective analysis was performed
      of all cases of sonographically suspected hydatidiform mole and histologically
      proven hydatidiform mole presenting to the Early Pregnancy Unit of an inner city
      hospital over a 4-year period. The sensitivity and positive predictive value
      (PPV) of ultrasound in the detection of histologically proven hydatidiform mole
      was calculated. RESULTS: The study group consisted of 90 women; 56 were suspected
      of having hydatidiform mole on ultrasound, and of these 27 (48%) had hydatidiform
      mole confirmed after histopathological examination of the products of conception,
      while no changes suggestive of hydatidiform mole were present in the other 29
      cases. Overall, 61 women had hydatidiform mole confirmed on histology-41 (67%)
      partial hydatidiform moles (PHM) and 20 (33%) complete hydatidiform moles (CHM).
      The ultrasound findings in the 34 cases not suspected of hydatidiform mole were
      an empty sac in 8/34 (24%) women and a delayed miscarriage in the other 26/34
      (76%). The overall sensitivity and positive predictive value for the ultrasound
      diagnosis of hydatidiform mole was 44% and 48%, respectively. For PHMs the
      respective values were 20% and 22% and for CHMs they were 95% and 40%.
      CONCLUSION: Ultrasonography is more reliable for diagnosing CHMs than for PHMs.
      Overall, the sensitivity of ultrasound for accurately predicting hydatidiform
      mole is 44%, and one in two women with an abnormal scan will have the disease
      confirmed on histology.

PMID- 17201013
TI  - Targeted therapy for threatened preterm labor based on sonographic measurement of
      the cervical length: a randomized controlled trial.
AB  - OBJECTIVE: False positive diagnosis of preterm labor is common. As a consequence,
      medications including corticosteroids to promote fetal lung maturity and
      tocolysis are prescribed unnecessarily. We tested the hypothesis that management
      of threatened preterm labor based on measurement of cervical length by
      ultrasonography can reduce the number of women who receive inappropriate
      treatment. METHODS: Forty-one women with threatened preterm labor for whom a
      clinical decision was made to prescribe antenatal corticosteroids and tocolysis
      were randomized to have their cervical length measured by transvaginal ultrasound
      (n=21) or to receive therapy as planned (n=20). Fourteen women in the ultrasound
      group had a cervix longer than 15 mm and the therapy was withheld, while the
      other seven with a short cervix were managed in the same way as the control
      group. RESULTS: Three women (14%) in the ultrasound group were treated
      inappropriately with antenatal corticosteroids because they remained undelivered
      for more than a week. This compared favorably with the control group where 18 out
      of 20 (90%) received corticosteroids unnecessarily (relative risk (RR) 0.16; 95%
      confidence interval (CI), 0.05-0.39). Tocolysis was given to only seven women
      (33.3%) in the ultrasound group compared with 20 (100%) in the control group (RR
      0.3; 95% CI, 0.15-0.54). There were no babies in either group who were born
      prematurely without being given a full course of antenatal corticosteroid
      therapy. CONCLUSION: Women with threatened preterm labor and cervical length more
      than 15 mm should not receive tocolysis. The issue of the safety of withholding
      corticosteroid therapy in this clinical scenario warrants further study.

PMID- 17201015
TI  - Re: ductus venosus shunting in growth-restricted fetuses and the effect of
      umbilical circulatory compromise.

PMID- 17201016
TI  - Reliability and validity of tissue volume measurement by three-dimensional
      ultrasound: an experimental model.
AB  - OBJECTIVE: To determine the validity and the intra- and interobserver reliability
      of volume measurements of an endometrium-like model using a three-dimensional
      (3D) ultrasound rotational technique. METHODS: A 3D ultrasound dataset was
      obtained from a sample of bovine liver containing a portion of chicken chest
      muscle (CCM). The process was repeated seven times using pieces of CCM of
      different sizes, resulting in seven datasets. Each portion of CCM was then placed
      in a water-filled volume-scaled tube and the 'actual' volumes were calculated by
      water displacement. For each dataset, ten volumes were calculated by each of two
      observers using a (VOCAL) with a 15 degrees rotational step. Reliability was
      assessed by calculating intraclass correlation coefficients (ICC) and validity by
      examining the percentage difference from the actual volume using limits of
      agreement. RESULTS: The volume measurement of organic tissues using the 3D
      ultrasound rotational method was highly reliable (intraobserver ICC, 0.998 for
      Observer 1 and 0.997 for Observer 2; interobserver ICC, 0.997) and valid (the
      bias and 95% limits of agreement of the percentage difference from the actual
      volume was only 0.57 (-3.07 to 4.21) % for Observer 1 and - 0.17 (-4.34 to 4.0) %
      for Observer 2). CONCLUSIONS: The 3D sonographic measurement, using VOCAL with a
      15 degrees rotational step, of small and irregular tissues is reliable and valid,
      suggesting that it is a useful technique for measurement of the endometrial
      volume and other volumes of similar size.

PMID- 17201017
TI  - Does three-dimensional power Doppler ultrasound help in discrimination between
      benign and malignant ovarian masses?
AB  - OBJECTIVES: To determine if tumor vascularity as assessed by three-dimensional
      (3D) power Doppler ultrasound can be used to discriminate between benign and
      malignant ovarian tumors, if adding 3D power Doppler ultrasound to gray-scale
      imaging improves differentiation between benignity and malignancy, and if 3D
      power Doppler ultrasound adds more to gray-scale ultrasound than does two
      dimensional (2D) power Doppler ultrasound. METHODS: One hundred and six women
      scheduled for surgery because of an ovarian mass were examined with transvaginal
      gray-scale ultrasound and 2D and 3D power Doppler ultrasound. The color content
      of the tumor scan was rated subjectively by the ultrasound examiner on a visual
      analog scale. Vascularization index (VI), flow index (FI) and vascularization
      flow index (VFI) were calculated in the whole tumor and in a 5-cm(3) sample taken
      from the most vascularized area of the tumor. Logistic regression analysis was
      used to build models to predict malignancy. RESULTS: There were 79 benign tumors,
      six borderline tumors and 21 invasive malignancies. A logistic regression model
      including only gray-scale ultrasound variables (the size of the largest solid
      component, wall irregularity, and lesion size) was built to predict malignancy.
      It had an area under the receiver-operating characteristics (ROC) curve of 0.98,
      sensitivity of 100%, false positive rate of 10%, and positive likelihood ratio
      (LR) of 10 when using the mathematically best cut-off value for risk of
      malignancy (0.12). The diagnostic performance of the 3D flow index with the best
      diagnostic performance, i.e. VI in a 5-cm(3) sample, was superior to that of the
      color content of the tumor scan (area under ROC curve 0.92 vs. 0.80, sensitivity
      93% vs. 78%, false positive rate 16% vs. 27% using the mathematically best cut
      off value). Adding the color content of the tumor scan or FI in a 5-cm(3) sample
      to the logistic regression model including the three gray-scale variables
      described above improved diagnostic performance only marginally, an additional
      two tumors being correctly classified. CONCLUSIONS: Even though 2D and 3D power
      Doppler ultrasound can be used to discriminate between benign and malignant
      ovarian tumors, their use adds little to a correct diagnosis of malignancy in an
      ordinary population of ovarian tumors. Objective quantitation of the color
      content of the tumor scan using 3D power Doppler ultrasound does not seem to add
      more to gray-scale imaging than does subjective quantitation by the ultrasound
      examiner using 2D power Doppler ultrasound.

PMID- 17201018
TI  - The value of measuring endometrial thickness and volume on transvaginal
      ultrasound scan for the diagnosis of incomplete miscarriage.
AB  - OBJECTIVE: To identify ultrasound measurements that are the best predictors of
      the presence of retained products of conception (RPOC) within the uterine cavity
      in women with clinical diagnosis of incomplete miscarriage. METHODS: This was a
      prospective observational study, set in a dedicated early pregnancy assessment
      unit in a London teaching hospital. Endometrial thickness and the volume of
      suspected retained products of conception were measured by transvaginal
      ultrasound scan preoperatively. Indications for surgical intervention were heavy
      vaginal bleeding or continuous bleeding lasting > 7 days. The main outcome
      measure was histological evidence of chorionic villi in surgical specimens.
      RESULTS: Among the patients, 109 (85%) had evidence of chorionic villi on
      histology, whilst decidua was only found in the remaining 19 (15%). There was no
      identifiable cut-off for endometrial thickness or volume that could be used to
      differentiate between retained products of conception and decidua. CONCLUSION:
      Measurements of endometrial thickness or volume on ultrasound scan are not good
      tests for diagnosing an incomplete miscarriage.

PMID- 17201019
TI  - Assessing somatic symptoms.

PMID- 17201020
TI  - Breastfeeding.

PMID- 17201021
TI  - Is salmeterol safe in asthma?

PMID- 17201023
TI  - Pipeline problems are increasing the urge to merge.

PMID- 17201022
TI  - What's in a number?
AB  - Ten years ago, the first estimates of the existing number of drug targets were
      made. This month's issue features an article and poster that together summarize
      current drug targets and associated characteristics, providing a basis to better
      understand the potential for future therapeutic exploitation.

PMID- 17201024
TI  - Andrea Pfeifer.

PMID- 17201025
TI  - Avoiding premature licensing.

PMID- 17201026
TI  - Panitumumab.

PMID- 17201027
TI  - Circumventing the cut-off for enrichment analysis.
AB  - Three tools for threshold-free enrichment analysis of microarray data are
      introduced: GSEA (gene set enrichment analysis), ermineJ and DRIM (discovering
      rank imbalanced motifs). GSEA offers an interface to a specific algorithm and a
      well-defined pipeline for the identifying enrichment in diverse gene sets and the
      creation of signature profiles. ermineJ offers a combined front end to three
      different algorithms, two of which perform a cut-off-free enrichment analysis.
      DRIM comprises an implementation of a new algorithm and is specifically designed
      for the search of new transcription-factor-binding sites based on expression
      patterns. Together, these tools demonstrate an emerging trend in high-throughput
      data analysis-the joint analysis of raw results with external knowledge.

PMID- 17201028
TI  - Long-term management strategies to achieve optimal function in patients with
      bipolar disorder.
AB  - Predictors of poor functional outcome in patients with bipolar disorder include
      psychiatric and medical comorbidity, interepisode subsyndromal symptoms,
      psychosis during manic or mixed episode, and low premorbid functioning. Cognitive
      dysfunction may also contribute to functional impairment. Psychosocial
      intervention has shown success in improving syndromal outcomes for people with
      bipolar disorder. Lithium, lamotrigine, olanzapine, and aripiprazole have all
      shown substantial improvements in relapse rates compared with placebo.
      Combination therapy with antipsychotics and antidepressants has also been shown
      to produce improvement in symptoms in people with bipolar disorder. However,
      limited evidence is available for the effects of these treatments on cognitive
      outcomes. This review discusses treatment strategies for the long-term management
      of bipolar disorder and functional outcome measures associated with these
      treatments.

PMID- 17201029
TI  - New directions in the treatment of atypical depression.
AB  - Atypical depression, one of the 4 historically important ways of subdividing
      depression, was first used by West and Dally to describe a patient subgroup that
      was nonresponsive to imipramine but responsive to iproniazid. The definition was
      later refined to include reverse vegetative and hysteroid dysphoria symptoms,
      presaging adoption of the current DSM definition in 1984. However, focusing on
      hysteroid dysphoria symptoms drew attention away from anxiety symptoms, some of
      which are more strongly linked to atypical depression. Studies that have
      attempted to validate atypical depression have reinforced reverse vegetative
      symptoms criteria and have shown that atypical depression is probably more common
      than melancholia. Studies suggest that atypical depression is not preferentially
      responsive to monoamine oxidase inhibitors, but rather less responsive to
      tricyclic antidepressants.

PMID- 17201030
TI  - Theme issue on poverty and human development: Call for papers on interventions to
      improve health among the poor.

PMID- 17201031
TI  - My patient power revolution.

PMID- 17201032
TI  - Suicide and documentation: a must-read.

PMID- 17201033
TI  - Suicide and documentation: a must-read.

PMID- 17201034
TI  - Suicide and documentation: a must-read.

PMID- 17201035
TI  - Language and discrimination.

PMID- 17201036
TI  - Pulmonary lymphangioleiomyomatosis in combination with uterine leiomyoma in a
      postmenopausal woman.

PMID- 17201037
TI  - Patient's page. Vitamin K for newborns.

PMID- 17201038
TI  - Feline practitioners reach out.

PMID- 17201040
TI  - Sees need for balance of animal welfare with other issues.

PMID- 17201039
TI  - New pastures in production medicine.

PMID- 17201041
TI  - Bibliography. Current world literature. Degenerative and cognitive diseases.

PMID- 17201042
TI  - [Adrenergic beta-Antagonists in prevention of cardiovascular complications in
      major non-cardiac surgery].

PMID- 17201043
TI  - [New achievements in the percutaneous transcatheter treatment of congenital heart
      disorders].

PMID- 17201044
TI  - The microbial hydroxylation of levonorgestrel.
AB  - The microbial transformation of levonorgestrel (1) by Cunningham elegans resulted
      in the formation of five hydroxylated metabolites, 13-ethyl-10beta, 17beta
      dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one(2), 13-ethyl-6beta,17beta
      dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (3) 13-ethyl 6beta, 10beta,
      17beta-trihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (4) 13-ethyl-15alpha
      17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (5) and 13-ethyl
      11alpha, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4en-20-yn-3-one. The
      fermentation of one with Rhizopus stolonifer, Fusarium lini and Curvularia lunata
      afforded compound 2 as a major metabolise. These metabolites were structurally
      characterized on the basis of spectroScopic techniques. Metabolite 6 was
      identified as a new compound. Compounds 2 2 ad 5 displayed inhibitory activity
      against the acetylcholinesterase ( AChE, EC. 3.1.1.7) with IC50 values of 79.2
      and 24.5 microM, respectively. The metabolites 2 and 5 also showed inhibitory
      activity against the butyryLcholinesterase ( BChE, E.C 3.1.1.8) with IC50 values
      ranging between 9.4 and 309.8 microM.

PMID- 17201046
TI  - Medical risk in patients with bipolar disorder and schizophrenia.
AB  - Patients with schizophrenia and bipolar disorder are vulnerable to developing key
      modifiable risk factors for cardiovascular disease, such as obesity, smoking,
      hypertension, dyslipidemia, and type 2 diabetes mellitus. In addition, mood
      stabilizers, anticonvulsants, and antipsychotic medications, which are commonly
      used to treat schizophrenia and bipolar disorder, have been linked to risk for
      adverse metabolic changes in patients. This review reports the prevalence of
      medical risk factors in the general population as well as in those patients with
      schizophrenia or bipolar disorder and discusses treatment strategies and
      lifestyle changes that patients can make in order to reduce their risks for
      certain diseases.

PMID- 17201045
TI  - The art and science of switching of antipsychotic medications, part 1.
AB  - In the presentation "Prevalence of and Factors Influencing the Switching of
      Antipsychotic Medications," Weiden defines the recovery approach for the
      treatment of schizophrenia, focuses on reasons for switching antipsychotic
      medications, and offers recommendations for evaluating switch studies. In
      "Combining and Switching Medications in Bipolar Disorder," Young discusses the
      similarities and differences between schizophrenia and bipolar disorder, offers
      recommendations for switching medications in bipolar disorder, and evaluates
      studies of atypical antipsychotics in the treatment of bipolar disorder.
      Buckley's presentation, "Differential Pharmacology of Atypical Antipsychotics:
      Clinical Implications," examines response rates in patients with schizophrenia
      after switching antipsychotic medications, outlines receptor-binding profiles of
      atypical antipsychotics, highlights adverse events that may occur when switching
      antipsychotic medications, and offers recommendations for treating those adverse
      events.

PMID- 17201047
TI  - Professional misconduct--sexual relationship with a patient.

PMID- 17201048
TI  - Professional misconduct--inadequate care.

PMID- 17201049
TI  - Professional misconduct--forgery to obtain drugs.

PMID- 17201050
TI  - Bibliography. Current world literature. History and philosophy.

PMID- 17201051
TI  - Bibliography. Current world literature. Clinical therapeutics.

PMID- 17201052
TI  - Classification is not EZ.

PMID- 17201054
TI  - Bibliography. Current world literature. Technology, education and training.

PMID- 17201053
TI  - Double-layered TiO2-SiO2 nanostructured films with self-cleaning and
      antireflective properties.
AB  - Dual function of self-cleaning and antireflection can be created in double
      layered TiO2-SiO2 nanostructured films. The film were prepared by (1) layer-by
      layer deposition of multilayered SiO2 nanoparticles with
      polydiallyldimethylammonium (PDDA) cations, (2) layer-by-layer deposition of
      multilayered titanate nanosheets with polications on PDDA/SiO2 multilayer films,
      and (3) burning out the polymer and converting titanate nanosheets into TiO2 by
      hearing at 500 degrees C. The as-prepared films, consisting of a porous SiO2
      bottom layer and a dense TiO2 top layer, improved the transmittance of glass or
      quartz substrates, as demonstrated by transmission spectra collected at normal
      incidence. The photocatalytic properties of the films were studied by the change
      of the water contact angle together with the decay of the IR absorption of the
      hydrocarbon chain of octadecylphosphonic-acid-modified films under 2.6 mW cm-2 UV
      illumination. Both the antireflective and the photocatalytic properties of the
      films were dependent on the number of PDDA/nanosheet bilayers deposited. however,
      excellent surface wettability of the films for water was obtained, independent of
      the preparation conditions. The experimental findings are discussed in terms of
      the special structure of the double-layered nanostructured film.

PMID- 17201055
TI  - [Minutes from the May 19th, 2006 meeting of the Oncology and Radiotherapy
      College. Location: National Institute of Oncology, Conference Hall. Present are
      16 College members and invited guests].

PMID- 17201056
TI  - [Minutes from the June 23rd, 2006 meeting of the Oncology and Radiotherapy
      College. Location: National Institute of Oncology, Conference Hall. Present are
      16 College members].

PMID- 17201057
TI  - [DNA structure from A to Z--biological implications of structural diversity of
      DNA].
AB  - Deoxyribonucleic acid (DNA) is a biopolymer of nucleotides, usually adopting a
      double-stranded helical form in cells, with complementary base pairing holding
      the two strands together. The most stable is B-DNA conformation, although
      numerous other double helical structures can occur under specific conditions (A
      DNA, Z-DNA, P-DNA). The existence of multiple-stranded (triplex, tetraplex) forms
      in vivo and their biological function in cells are subject of intensive studies.

PMID- 17201058
TI  - [Chemically methylated DNA repair in Escherichia coli--the role of alkB protein].
AB  - Methylating agents belong to mutagens occurring most frequently in our
      environment. They methylate mainly the nitrogen bases in DNA and RNA, affecting
      their functions. In E. coli the alkylated bases are repaired by proteins and
      enzymes either permanently present in the cells (Ogt, Ada) or produced
      transiently (Ada, AlkB, AlkA, Aid), after induction of the Ada defence system.
      Alkylating agents induce also the SOS system, which enhances the synthesis of
      about 40 proteins, including those participating in recombination, replication
      and mutagenesis of DNA. All DNA interactions, modifications and repairs
      constitute an amazing and highly efficiently functioning cellular system. Among
      the repair proteins there are some which affect the alkylated bases in a non
      conventional way, very rarely occurring in nature. Especially amazing is the
      mechanism of action of dioxogenase AlkB, which combines the repair of methyl-,
      ethyl- and etheno-base derivatives with oxidation and dissociation of the
      modified groups, leading to direct recovery of natural bases. This review
      attempts to elucidate the role of the individual proteins involved in the repair
      processes.

PMID- 17201059
TI  - [The innate antiretroviral defense of human cells, based on the DNA editing].
AB  - The editing process may play an essential role in the antiviral cell defense. The
      human cytidine deaminase APOBEC3G, that catalyses the deoxycytidine to
      deoxyuridine deamination reaction in the reverse transcript of the HIV-1 genome,
      leads to instability of the viral DNA, if only HIV-1 virion is defective and
      lacks the Vif protein. This mechanism has an affect on G-A hipermutation
      appearing in the provirus DNA and defective HIV-1 viral RNA, yielded in infected
      cell. Such hipermutation has previously been discovered in the viral HIV-1
      genome, produced in peripheral blood mononuclears that were long-term cultured
      after collection from infected patient. Probably, the deamination reaction that
      is inhibited in the wild type HIV-1 by the Vif protein, occurs rarely during
      infection and thus increases viral diversity and drug's resistance. In this
      review, we present the results of latest studies concerning the mechanism of
      viral DNA deamination, specifity of this process and APOBEC3G - HIV-1 Vif
      interactions, that may be useful in designing the new anti-HIV therapies.

PMID- 17201061
TI  - [Aptamers in clinical diagnostics].
AB  - Aptamers are single-stranded DNA or RNA oligonucleotides selected in vitro from
      combinatorial libraries in a process called SELEX (Systematic Evolution of
      Ligands by EXponential Enrichment). Aptamers play a role of artificial nucleic
      acid ligands that can recognize and bind to various organic or inorganic target
      molecules with high specificity and affinity. They can discriminate even between
      closely related targets and can be easily chemically modified for radioactive,
      fluorescent and enzymatic labeling or biostability improvement. Aptamers can thus
      be considered as universal receptors that rival antibodies in diagnostics as a
      tool of molecular recognition. To date aptamers have been successively used
      instead of monoclonal antibodies in flow cytometry, immunochemical sandwich
      assays and in vivo imaging as well to detect wide range of small or large
      biomolecules.

PMID- 17201060
TI  - [Trans-acting short interfering RNAs].
AB  - RNA is now considered a key factor in the regulation of gene expression. There
      are several classes of small regulatory RNAs in plants, functioning in
      posttranscriptional gene silencing (PTGS) or epigenetic DNA modification. Trans
      acting short interfering RNAs (tasiRNAs) form a class of small regulatory RNAs
      which has been distinguished only recently. To date, five genes encoding tasiRNAs
      have been identified in Arabidopsis thaliana. TasiRNAs derive from non-coding RNA
      precursors which are initially targeted for cleavage by a miRNA. Cleavage
      products are then converted into dsRNAs by a RNA dependent RNA polymerase and
      sequentially cleaved into 21-nt tasiRNAs. Like the majority of plant miRNAs,
      tasiRNAs regulate gene expression at the posttranscriptional level, guiding
      cleavage of ARF and PPR transcripts. Here, we briefly present tasiRNAs and
      speculate whether they form a homogeneous class of siRNAs.

PMID- 17201062
TI  - [Bacterial type II topoisomerases as targets for antibacterial drugs].
AB  - Bacterial type II DNA topoisomerases are essential enzymes for correct genome
      functioning and cell growth. Gyrase is responsible for maintaining negative
      supercoiling of bacterial chromosome, whereas topoisomerase IV acts in
      disentangling daughter chromosomes following replication. Type II DNA
      topoisomerases possess an ATP binding site, which can be treated as a target for
      antibacterial drugs. Resolving crystal structures of protein fragments consisting
      of an ATP binding site complexed with ADPNP/antibiotics have proven to be
      valuable for the understanding of the mode of action of existing antibacterial
      agents and presented new possibilities for novel drug design. Coumarins,
      quinolones and cyclothialidines are diverse group of antibiotics that interfere
      with type II DNA topoisomerases, however their mode of action is different.
      Recently a new class of antibiotics, simociclinones, was characterized. Their
      mechanism of action towards gyrase is entirely distinct from already known modes
      of action, therefore demonstrating the potential for development of novel anti
      bacterial agents.

PMID- 17201063
TI  - [AMP-activated protein kinase--the key role in metabolic regulation].
AB  - AMP-activated protein kinase (AMPK) is the central component of a protein kinase
      cascade that acts as an energy sensor maintaining the energy balance at the
      cellular as well as at the whole body level. Within the healthy cell, metabolic
      stress leading to an increase in AMP concentration results in AMPK activation.
      Once activated, AMPK "switches off" many anabolic pathways e.g. fatty acid and
      protein synthesis while "switches on" catabolic pathways such as fatty acid
      oxidation or glycolysis which serve to restore intracellular ATP level. Adipocyte
      derived hormones leptin and adiponectin activate AMPK in peripheral tissues
      increasing energy expenditure. AMPK also regulates food intake due to response to
      hormonal and nutrient signals in hypothalamus. Antidiabetic drugs that mimic the
      action of insulin activate the AMPK signaling pathways. Further studies are
      needed to clarify the importance of the AMPK activation for therapeutic effects
      of this drugs.

PMID- 17201064
TI  - [The heat shock response and HSP70 gene expression in male germ cells].
AB  - Apoptosis of spermatogenic cells is an essential process that allows to maintain
      correct proportion between somatic and germ cells. In addition, apoptosis induced
      by cellular stress is an important checkpoint mechanism that eliminates damaged
      male germ cells. The response to cellular stress (e.g. hyperthermia) in somatic
      cells includes activation of the heat shock transcription factor 1 (HSF1) leading
      to induction and accumulation of the heat shock proteins (HSPs), mainly HSP70i,
      which allows cell survival. In major contrast, in meiotic and post-meiotic germ
      cells Hsp70i genes are not induced in elevated temperature. Instead, activation
      of HSF1 leads to caspase-3-dependent apoptosis and spermatogenic cells are
      actively eliminated. Although HSP70i proteins are repressed in spermatocytes and
      spermatids, another HSP70 proteins are specifically expressed in those cells,
      which are necessary for spermatogenesis. However, Hsp70.2/Hst70 gene, the major
      testis-specific Hsp70 expressed mostly in spermatocytes, is down-regulated by
      HSF1 and spermatogenic cells undergoing stress-induced apoptosis lack
      HSP70.2/HST70 protein.

PMID- 17201065
TI  - [Plant ABC transporters--the family with tradition].
AB  - ATP binding cassette (ABC) transporters, which are found in all species, are
      known mainly for their ability to confer drug resistance. They have been
      thoroughly studied in mammals, where they became the center of interest for
      clinical reasons related to the resistance of tumor cells to chemotherapy
      treatment. Less is known about plant members of the ABC family, however, growing
      number of reports on their role in different physiological processes attract
      attention. The vacuolar ABC transporters in plants characterized to date are
      involved in the intracellular sequestration of cytotoxins (e.g. herbicides), as
      well as the products of endogenous metabolism like chlorophyll catabolites.
      Others localized within plasma membrane are active in the transport of secondary
      metabolites or phytohormones. Finally certain transporters are present in cell
      organelles and play a role in such processes as P oxidation. Here, we briefly
      introduce these proteins, and describe structural characteristic and
      physiological aspect of their activity in a plant cell.

PMID- 17201066
TI  - [Multifunctional 14-3-3 proteins of plant cell].
AB  - The 14-3-3 proteins are a family of highly conserved proteins found in all
      eukaryotes - from the yeasts to mammals. They regulate several cellular processes
      recognizing unique conservative, mostly phosphorylated motif of partner proteins.
      Binding of the 14-3-3 proteins regulates their partners through a variety of
      mechanisms, such as altering their catalytic activity, subcellular localization,
      stability or altering their interactions with other protein molecules. The native
      14-3-3 proteins are present in form of homo- and hetero-dimers. The most
      structurally variable N-and C-termini are responsible for isoform specific
      protein-protein interactions, and cellular localization. In plant cell, 14-3-3
      proteins appear to play an important role in regulation of key enzymes of carbon
      and nitrogen metabolism, modulation ion pumps and channels. They are also
      involved in signal transduction pathways and even in gene expression.

PMID- 17201067
TI  - [Opioid receptors and their selective ligands].
AB  - Opioid receptors (micro, delta, and kappa) belong to a large family of G protein
      coupled receptors and play an important physiological role. Stimulation of these
      receptors triggers analgesic effects and affects the function of gastrointestinal
      tract. The discovery of opioid peptides, which are endogenous ligands of opioid
      receptors, including delta-selective enkephalins, kappa-selective dynorphins, and
      micro-selective endomorphins, initiated their structure-activity relationship
      studies. For the last 30 years, hundreds of analogs of opioid peptides have been
      synthesized in an effort to obtain the compounds more active, selective, and
      resistant to biodegradation than the endogenous ligands. Different unnatural
      amino acids, as well as cyclisation procedures, leading to conformationaly
      restricted analogs, were employed. All these modifications resulted in obtaining
      very selective agonists and antagonists with high affinity at micro-, dlta-, and
      kappa-opioid receptors, which are extremely useful tools in further studies on
      the pharmacology of opioid receptors in a mammalian organism.

PMID- 17201068
TI  - [Biochemical mechanisms of neurotoxic lead activity].
AB  - This article presents the latest study results on lead (Pb2+) neurotoxicity, in
      order to draw attention of the Polish public to the issue and initiate a nation
      wide programme eliminating lead contamination effects, especially in children. We
      discuss the after-effect of exposure to lead in concentrations lower than
      presently accepted as 'safe'. The pathway of lead transport to the brain, and the
      effects of lead accumulation in neurons, oligodendroglia and astroglia, are
      examined. We also present the impairing influence of lead on the cognitive brain
      functions and learning abilities as a result of affecting three main
      neurotransmission systems: dopaminergic, cholinergic and glutaminergic. The
      present knowledge on the influence of lead on receptors, neutransmitter release
      and synaptic proteins.

PMID- 17201070
TI  - Interleukin-6 in acute exercise and training: what is the biological relevance?
AB  - It is now recognized that contracting skeletal muscle may synthesize and release
      interleukin-6 (IL-6) into the interstitium as well as into the systemic
      circulation in response to a bout of exercise. Although several sources of IL-6
      have been demonstrated, contracting muscles contributes to most of the IL-6
      present in the circulation in response to exercise. The magnitude of the exercise
      induced IL-6 response is dependent on intensity and especially duration of the
      exercise, while the mode of exercise has little effect. Several mechanisms may
      link muscle contractions to IL-6 synthesis: Changes in calcium homeostasis,
      impaired glucose availability, and increased formation of reactive oxygen species
      (ROS) are all capable of activating transcription factors known to regulate IL-6
      synthesis. Via its effects on liver, adipose tissue, hypothalamic-pituitary
      adrenal (HPA) axis and leukocytes, IL-6 may modulate the immunological and
      metabolic response to exercise. However, prolonged exercise involving a
      significant muscle mass in the contractile activity is necessary in order to
      produce a marked systemic IL-6 response. Furthermore, exercise training may
      reduce basal IL-6 production as well as the magnitude of the acute exercise IL-6
      response by counteracting several potential stimuli of IL-6. Accordingly, a
      decreased plasma IL-6 concentration at rest as well as in response to exercise
      appears to characterize normal training adaptation.

PMID- 17201069
TI  - [Structure, function and mechanisms of action of ATPases from the AAA superfamily
      of proteins].
AB  - AAA ATPases are found in all living organisms. Their common feature is the
      presence of a highly conserved the AAA domain referred to as AAA module that is
      responsible for ATP binding and hydrolysis. The AAA domain is required for proper
      function of AAA proteins. It contains 200-250 residues, among them there are two
      classical motifs, Walker A (GX4GKT) and Walker B (HyDE). AAA proteins participate
      in variety of cellular processes, including cell-cycle regulation, protein
      proteolysis and disaggregation, organelle biogenesis and intracellular transport.
      Some of them function as molecular chaperones, subunits of proteolytic complexes
      or independent proteases (FtsH, Lon). They also act as DNA helicases and
      transcription factors. This review describes the structure, function and
      mechanisms of action of the most known AAA proteins.

PMID- 17201071
TI  - Exercise and Toll-like receptors.
AB  - Toll-like receptors (TLRs) are highly conserved trans-membrane proteins that play
      an important role in the detection and recognition of microbial pathogens. The
      key product of TLR signalling in antigen presenting cells is the production of
      inflammatory cytokines and proteins. The TLR pathway plays an important role in
      mediating whole body inflammation, which has been implicated in the development
      of chronic disease. An accumulation of chronic, low-grade inflammation is common
      in individuals that live a sedentary lifestyle; however, the mechanism underlying
      this connection is not fully understood. There is evidence to show that TLRs may
      be involved in the link between a sedentary lifestyle, inflammation, and disease.
      Recent studies have shown that both acute aerobic and chronic resistance exercise
      resulted in decreased monocyte cell-surface expression of TLRs. Furthermore, a
      period of chronic exercise training decreases both inflammatory cytokine
      production and the cell-surface expression of TLR4 on monocytes. These effects
      may contribute to post-exercise immunodepression and the reported higher
      susceptibility to infection in athletes. However over the long-term, a decrease
      in TLR expression may represent a beneficial effect because it decreases the
      inflammatory capacity of leukocytes, thus altering whole body chronic
      inflammation. The precise physiological stimulus mediating an exercise-induced
      decrease in cell-surface TLR expression is not known; however a number of
      possible signals have been implicated including anti-inflammatory cytokines,
      stress hormones and heat shock proteins.

PMID- 17201072
TI  - The implication of alterations in leukocyte subset counts on immune function.
AB  - Changes elicited by physical exercise in the numbers or the activity of blood T
      lymphocytes, NK cells and neutrophils are sometimes considered as indicators of
      altered immunocompetence. By comparing the pathological conditions, in which the
      changes in the numbers of cells resemble observations in the exercise studies,
      however we notice large discrepancies in the clinical manifestations.
      Supplementary information regarding the differences in cytokines and mediators
      responsible for altered distributions helps to explain this difference and the
      significance of altered distribution of the cells for immunocompetence.
      Alterations in the numbers and activities of T lymphocytes, NK cells and
      neutrophils may serve as markers of sympathetic and glucocorticoid activities,
      which per se may influence immunocompetence not necessarily deterioration.

PMID- 17201073
TI  - Systemic inflammatory responses to maximal versus submaximal lengthening
      contractions of the elbow flexors.
AB  - We compared changes in markers of muscle damage and systemic inflammation after
      submaximal and maximal lengthening muscle contractions of the elbow flexors.
      Using a cross-over design, 10 healthy young men not involved in resistance
      training completed a submaximal trial (10 sets of 60 lengthening contractions at
      10% maximum isometric strength, 1 min rest between sets), followed by a maximal
      trial (10 sets of three lengthening contractions at 100% maximum isometric
      strength, 3 min rest between sets). Lengthening contractions were performed on an
      isokinetic dynamometer. Opposite arms were used for the submaximal and maximal
      trials, and the trials were separated by a minimum of two weeks. Blood was
      sampled before, immediately after, 1 h, 3 h, and 1-4 d after each trial. Total
      leukocyte and neutrophil numbers, and the serum concentration of soluble tumor
      necrosis factor-alpha receptor 1 were elevated after both trials (P < 0.01), but
      there were no differences between the trials. Serum IL-6 concentration was
      elevated 3 h after the submaximal contractions (P < 0.01). The concentrations of
      serum tumor necrosis factor-alpha, IL-1 receptor antagonist, IL-10, granulocyte
      colony stimulating factor and plasma C-reactive protein remained unchanged
      following both trials. Maximum isometric strength and range of motion decreased
      significantly (P < 0.001) after both trials, and were lower from 1-4 days after
      the maximal contractions compared to the submaximal contractions. Plasma
      myoglobin concentration and creatine kinase activity, muscle soreness and upper
      arm circumference all increased after both trials (P < 0.01), but were not
      significantly different between the trials. Therefore, there were no differences
      in markers of systemic inflammation, despite evidence of greater muscle damage
      following maximal versus submaximal lengthening contractions of the elbow
      flexors.

PMID- 17201074
TI  - Physiological improvements and health benefits during an exercise-based
      comprehensive rehabilitation program in medically complex patients.
AB  - OBJECTIVES: To determine the effects of an exercise-based comprehensive
      rehabilitation program on the physiological, health, and cost benefit in
      medically complex patients. DESIGN: Case series SETTING: Comprehensive
      rehabilitation centers. PARTICIPANTS: Elderly chronically ill men (n = 39, age =
      75.3 +/- 1.4) and women (n = 74, age = 76.5 +/- 0.9 years). INTERVENTION:
      Patients participated in individualized physical therapy with therapeutic
      exercises (stretching, strengthening, endurance, balance, sitting and standing
      dynamic exercises) three times/week for three months under the supervision of a
      physician. MEASUREMENTS: Upper (back) and lower (leg flexors) extremity strength,
      aerobic power as measured by metabolic equivalents (METS) at 80% of age predicted
      maximal heart rate (APMHR), physical functioning and mental health as assessed by
      the Short Form-36 (SF-36) questionnaire, and medical events (falls, physician
      visits, and hospitalizations) questionnaire was collected at baseline and after
      three months of the program. RESULTS: Strength measures improved by approximately
      30% (P < 0.05) as well as aerobic power improved by approximately 25% (P < 0.05)
      over the three-month period. There were significant improvements in two of the SF
      36 Physical Component Scales: Physical Functioning (P < 0.05) and Role Physical
      (P < 0.05); plus, there were significant improvements in all four of the Mental
      Component Scales: Vitality (P < 0.05), Social Functioning (P < 0.05), Role
      Emotional (P < 0.05), and Mental Health (P < 0.05). There were significant
      reductions in fall rate (P < 0.05), physician visits (P < 0.05), and
      hospitalizations (P < 0.05). CONCLUSION: Patients improve physical capacity,
      which result in improvements in health status with concurrent reductions in
      healthcare utilization during a comprehensive rehabilitation program.

PMID- 17201075
TI  - Moderate exercise early after influenza virus infection reduces the Th1
      inflammatory response in lungs of mice.
AB  - We have previously shown that moderate exercise significantly increased survival
      after influenza virus (A/PR/8/34) infection in mice. We hypothesized that this
      brief duration of exercise would either increase innate immune defences and/or
      shift the immune response from a Th1 inflammatory to a Th2 anti-inflammatory
      response resulting in decreased lung pathology. Adult male BALB/cByJ mice (5-6
      months old) were infected with 50 microL of A/PR/8/34 virus (40HAU) intranasally
      and randomized to either an exercise (EX) or sedentary (SED) group. EX mice
      performed 20-30 min of moderate exercise (8-12 m/min) on a motorized treadmill 4
      hr post-infection and then exercised similarly for 4 consecutive days. SED mice
      were exposed to similar environmental conditions but did not exercise. Mice from
      both EX and SED groups were sacrificed 1, 3, or 5 days post-infection (p.i.) and
      lungs, mediastinal lymph nodes (MLNs) and spleens were harvested. EX
      significantly reduced total cellular infiltration and IFN-gamma gene expression
      in lungs at Days 3 and 5 p.i. and there was a qualitative shift in the expression
      of cytokines in the lung from a Th1 to a Th2 response. There was also a tendency
      toward a reduction in influenza M1 protein mRNA expression. There was no
      difference in IFN-beta protein levels between groups. These data suggest that
      moderate exercise when applied early after infection shifts the immune response
      away from a Th1 profile in mice infected with influenza virus. This exercise
      induced shift in immune response may be responsible for improved survival after
      influenza virus infection.

PMID- 17201076
TI  - Regulation of immediate early gene expression by exercise: short cuts for the
      adaptation of immune function.
AB  - Onset of physical activity induces a wide variety of rapid biophysical and
      biochemical responses that act on cells and lead to a wide range of phenotypic
      adaptations. Here we elucidate the role of immediate early gene (IEG) expression
      as a first line of transcriptional response that mediates protein neosynthesis
      and leads to adaptation of immune function. New posttranscriptional mechanisms
      have been described that speed up transcriptional responses. These include RNA
      RNA interactions such as those exploited by miRNAs and stimulus-dependent
      cytoplasmic polyadenylation. We describe these shortcuts that modulate expression
      and discuss the challenges of accurately measuring them using various
      transcriptomic screening and quantification approaches. Although there is high
      complexity of the upstream as well as the downstream pathways that lead to IEG
      expression, IEG expression itself may only show a limited number of response
      patterns. Focusing transcriptomic approaches in exercise immunology at the IEG
      level may facilitate the discovery of exercise-specific transcriptional
      signatures.

PMID- 17201078
TI  - The application of a modified technique of SCP under DHCA during total aortic
      arch replacement combined with stented elephant trunk implantation.
AB  - We reviewed the perfusion experiences of 60 cases with a modified technique of
      selected cerebral perfusion (SCP) under deep hypothermic circulatory arrest
      (DHCA) during ascending aorta and total aortic arch replacement combined with
      transaortic stented graft implantation into the descending aorta for acute and
      chronic type A aortic dissection. Right auxiliary artery cannulation was
      routinely used for cardiopulmonary bypass (CPB) and SCP in this procedure.
      Generally, this technique requires two main pumps for two arterial lines before
      we applied the modified technique; one for CPB and the other for SCP. In order to
      simplify the circuit of the extracorporeal circuit (ECC) to operate easily, the
      arterial line was separated into two branches with a Y-connector on the operating
      table, one for axillary artery perfusion and the other for graft perfusion
      connected to the ECC set-up. This method is easy for the perfusionist to install
      and convenient for the surgeon. This is a safe and simple to use modified
      technique for SCP under DHCA during ascending aorta and total aortic arch
      replacement combined with transaortic stented graft implantation into the
      descending aorta.

PMID- 17201077
TI  - Comparison of two different extracorporeal circuits on cerebral embolization
      during cardiopulmonary bypass in children.
AB  - OBJECTIVE: To compare the effect of two different extracorporeal circuits on the
      counts of high-intensity transient signals (HITS) during pediatric
      cardiopulmonary bypass (CPB). METHODS: Transcranial Doppler was used to detect
      HITS associated with extracorporeal sources during the period of aortic
      crossclamping in the middle cerebral artery of children undergoing CPB. Based on
      body size, children were assigned one of two extracorporeal circuits (A or B).
      Circuit A included a D-705 oxygenator and associated reservoir, and circuit B
      included a Lilliput oxygenator and reservoir. Patients were further classified
      into two groups according to the complexity of surgical repair: single simple
      lesions or multiple complex lesions. RESULTS: We studied 109 pediatric patients.
      Surgery for multiple complex lesions was associated with longer periods of aortic
      crossclamping and CPB (p < 0.0001). The median count of extracorporeal HITS was
      12 (25th, 75th percentiles: 3, 51). The type of extracorporeal circuit (p =
      0.012) and the complexity of surgical repair (p < 0.0001) had an effect on the
      HITS counts. The use of circuit A was associated with higher HITS counts during
      surgery for multiple complex lesions compared to single simple lesions (p <
      0.0001). Conversely, no differences were found with the use of circuit B between
      these two surgical groups (p > 0.25). During surgery for multiple complex
      lesions, patients treated with circuit A showed higher HITS counts than those
      with circuit B (p < 0.01), but there were no circuit-related differences in HITS
      counts (p = 0.30) during single simple lesions. CONCLUSION: Variations in the
      design characteristics of extracorporeal circuits can increase cerebral emboli
      during CPB in children. This may be related to the reduced ability of some
      circuits to remove emboli during long periods of CPB for complex congenital heart
      surgery.

PMID- 17201080
TI  - Prevention of cryoprecipitation during cardiopulmonary bypass in a patient with
      HIV-HCV co-infections.
AB  - BACKGROUND: There are no guidelines for the management of patients with
      cryoglobulins during cardiopulmonary bypass (CPB) necessitating core hypothermia.
      OBJECTIVE: To evaluate a simple, pragmatic protocol of in vitro temperature
      dependent cryoprecipitation of serum in patients with cryoglobulinemia before
      elective cardiac surgery with CPB. METHODS: A 44-year-old female patient was
      known for chronic hepatitis C and type III cryoglobulinemia. Elective surgery was
      planned for an aortic arch aneurysm. A differential serum cryoprecipitation
      profile was established in vitro prior to surgery. RESULTS: Whereas, at
      temperatures < or = 15 degrees C, cryoglobulin levels were > or = 0.112 g/L
      (normal value < 0.05 g/L), at 20 degrees C and above, the precipitate was < or =
      0.016 g/L. Accordingly, surgery was performed without any cryoglobulin-related
      complications at an extracorporeal circulation temperature of 22-24 degrees C, to
      minimise the risk of cryoprecipitation. CONCLUSION: In elective cases of surgery
      with CPB and hypothermia, temperature-dependent differential serum
      cryoprecipitation profile may be an easy and efficient way to assess a safe
      peroperative level of temperature to avoid complications due to cryoglobulins,
      without enhancing the patient's tissue ischemia risks.

PMID- 17201079
TI  - Delayed thrombin generation is not associated with fibrinopeptide formation
      during prolonged cardiopulmonary bypass with hirudin anticoagulation.
AB  - Patients with heparin-induced thrombocytopenia urgently requiring surgery with
      cardiopulmonary bypass (CPB) present a unique management challenge that must be
      addressed by the use of alternative anticoagulants. Although clinical success
      with the direct thrombin inhibitor hirudin has been reported, there is sparse
      information in the literature supporting the efficacy of this drug as an anti
      thrombotic to prevent fibrin formation during CPB. In this report, we describe
      the efficacy of this drug to prevent thrombin-mediated fibrin formation during
      CPB.

PMID- 17201082
TI  - The contribution of arterio-venous extracorporeal lung assist to gas exchange in
      a porcine model of lavage-induced acute lung injury.
AB  - This prospective large-animal study was performed to evaluate the contribution of
      arterio-venous extracorporeal lung assist (AV-ECLA) to pulmonary gas exchange in
      a porcine lavage-induced acute lung injury model. Fifteen healthy female pigs,
      weighing 50.3 +/- 3.8 kg (mean +/- SD), were included. After induction of general
      anaesthesia and controlled ventilation, an arterial line and a pulmonary artery
      catheter were inserted. Saline lung lavage was performed until the PaO2 decreased
      to 51 +/- 16 mmHg. After a stabilization period of 60 min, the femoral artery and
      vein were cannulated and a low-resistance membrane lung was interposed. Under
      apnoeic oxygenation, variations of sweep-gas flow were performed every 20 min in
      order to evaluate the membrane lung's efficacy, in terms of carbon dioxide (CO2)
      removal and oxygen (O2) uptake. Although AV-ECLA is highly effective in
      eliminating CO2, if combined with apnoeic oxygenation, normocapnia was not
      achievable. AV-ECLA's contribution to oxygenation during severe hypoxemia was
      antagonized by a significant increase in the pulmonary shunt fraction.

PMID- 17201081
TI  - Isolated lung perfusion for pulmonary metastases, a review and work in progress.
AB  - Pulmonary metastasectomy is a widely accepted treatment for many patients with
      pulmonary metastases from various solid tumors. Nevertheless, 5-year survival is
      disappointing, with rates of 25-40%, and many patients develop recurrences.
      Isolated lung perfusion (ILuP) is a promising new technique to deliver high-dose
      chemotherapy to the lungs, while minimising systemic toxicities. This procedure
      is technically safe and feasible; however, clinical value and efficacy remain
      unclear. The aim of this paper is to give a review of literature on ILuP in
      humans, and to describe the development of the perfusion procedure in our
      institute.

PMID- 17201083
TI  - Anticoagulation management in patients undergoing open heart surgery by activated
      clotting time and whole blood heparin concentration.
AB  - OBJECTIVE: To investigate the changes in perioperative anticoagulation management
      using a heparin-concentration-based system (HMS), and its effect on postoperative
      outcome. METHODS: A total of 39 patients undergoing elective primary open heart
      surgery were randomly assigned to a heparin-concentration-based system approach
      (study group: 17 patients) or a standard ACT-based anticoagulation system
      (control group: 22 patients). MEASUREMENTS AND MAIN RESULTS: Patients in the
      study group received a statistically significant higher dose of heparin (median
      29000 IU with IQR 22 500-33 500 IU versus median 19 000 IU with IQR 17 775-21 500
      IU; p < 0.001) and a smaller dose of protamine (median 170 mg with IQR 145-190 mg
      versus median 200 mg with IQR 180-250 mg; p = 0.008) compared to the control
      group. Postoperative platelet count was significantly higher in the study group
      (164 +/- 45 x 10(9)/L versus 125 +/- 27 x 10(9)/L, p = 0.002). None of the study
      patients, but six patients in the control group required transfusion of blood
      products (p = 0.02). No differences were recorded in postoperative antithrombin
      activity, bleeding, and other clinical outcomes. CONCLUSION: The HMS system, by
      facilitating maintenance of a stable heparin concentration, and by determining an
      appropriate dose of protamine, is associated with reduced platelet consumption
      and does not increase AT-III consumption and postoperative bleeding.

PMID- 17201084
TI  - Effects of centrifugal and roller pumps on survival of autologous red cells in
      cardiopulmonary bypass surgery.
AB  - BACKGROUND: Either a roller pump or a centrifugal pump can be used in the
      extracorporeal circuit during surgery with cardiopulmonary bypass. In this study,
      we assessed the effect of these two pumps on the 24-h post-transfusion survival
      values of autologous red blood cells (RBC). STUDY DESIGN AND METHODS: Fourteen
      male patients subjected to extracorporeal bypass procedures were studied. In
      seven patients, the autologous red cells were collected following the
      cardiopulmonary bypass procedure using the roller pump, and in seven patients,
      autologous red cells were collected following the cardiopulmonary procedure using
      the centrifugal pump. The 24-h post-transfusion survival values of the autologous
      RBC were measured using the 51 disodium chromate/99m technetium double isotope
      procedure. The effects of the extracorporeal bypass procedures using the roller
      pump and the centrifugal pump were also assessed by the measurements of
      hematocrit, platelet count, plasma hemoglobin, and serum lactate dehydrogenase
      levels. RESULTS: The 51 disodium chromate 24-h post-transfusion survival values
      of the autologous RBC were similar whether the roller pump or the centrifugal
      pump was used in the extracorporeal circulation, as were the hematocrit, platelet
      count, plasma hemoglobin and serum lactate dehydrogenase levels. CONCLUSION: The
      24-h post-transfusion survival values of autologous RBC, measured by the 51
      disodium chromate/99m technetium double isotope procedure, were not significantly
      different, whether the roller pump or the centrifugal pump was used in the
      extracorporeal circuit using membrane oxygenators during cardiopulmonary surgical
      procedures.

PMID- 17201085
TI  - A new oxygenator change-out system and procedure.
AB  - Official reports relate that, in the US, one patient/month dies as a result of
      the emergency oxygenator change-out procedure, and the permanent injury of some
      patients is the result of current oxygenator change-out procedures or oxygenator
      failures, both in extracorporeal circulation (ECC) and extracorporeal membrane
      oxygenation (ECMO). The aim of this article is to evaluate a new system and
      procedure, dedicated to oxygenator change-out, represented by two three-way
      stopcocks inserted in the ECC line in use. A dedicated back-up oxygenator and
      circuit can be easily primed and connected to the dedicated connector on the
      stopcocks, then blood flow is diverted to the new oxygenator without interruption
      of the ECC. Tests performed showed that oxygenator change-out can be completed by
      perfusionists in 62.13 +/- 11.12 sec. Results obtained show that the new system
      and procedure allows fast, safe and reproducible oxygenator change-out without
      interruption of the ECC.

PMID- 17201086
TI  - Leucocyte depletion in a drowning victim during rewarming with extracorporeal
      circulation may limit pulmonary oedema.
AB  - INTRODUCTION: We report two drowning victims with hypothermic circulatory arrest
      who were resuscitated with the use of extracorporeal circulation (ECC). The first
      patient developed severe post-bypass pulmonary oedema and inspired us to use a
      leucocyte-depletion filter in the second patient to attenuate leucocyte-mediated
      pulmonary reperfusion injury. METHODS: In the first patient, a standard
      extracorporeal circuit was used. In the second patient, systemic leucocyte
      depletion was applied using leucocyte-depletion filters (Pall RS 1, Pall,
      Portsmouth, UK), in the venous side of the extracorporeal circuit. Circulating
      leucocyte counts were measured and arterial blood gas analysis and chest X-rays
      were performed. RESULTS: Both patients showed a decrease of the circulating
      leucocyte counts during rewarming and had nearly similar leucocyte counts on
      arrival at the intensive care unit (ICU). The first patient developed severe
      pulmonary oedema, with poor arterial blood gases, whereas the second patient, who
      had leucocyte-depletion by filtration, did not develop severe pulmonary oedema,
      and had good arterial blood gases. CONCLUSION: Profound leucocyte-depletion by
      means of filtration may have contributed to limit leucocyte-mediated pulmonary
      reperfusion injury.

PMID- 17201087
TI  - Re: Likosky and Groom. A patient and system's level perspective.

PMID- 17201088
TI  - Selective increase in serum IgE following enfuvirtide administration in HIV-1
      infected multidrug resistant patients.
AB  - Enfuvirtide (ENF) is the first HIV-1 entry inhibitor used in clinical practice
      and is currently administered via the subcutaneous route. We here evaluated
      whether ENF administration leads to a change in humoral parameters, including
      IgE, possibly related to ENF-associated injection site reactions (ISRs). A 24
      week prospective study was conducted in multidrug resistant patients enrolled in
      the ENF Early Access Program characterized by CD4 counts < or =100
      cells/microlitre and no other active antiretroviral drug. Licensed commercial
      laboratory assays were used to measure the parameters considered in this study.
      Results are reported as medians (interquartiles IQR). Statistical analyses were
      performed using Wilcoxon sign rank, Wilcoxon rank sum and Kruskall Wallis tests.
      Total IgM, IgA and IgG did not change significantly throughout the study.
      Conversely, a significant increase in IgE was observed in all patients, in those
      with normal as well as in those with altered IgE at baseline (BL). ISRs such as
      induration and number of nodules were more frequent in patients with altered BL
      IgE. IgE increased significantly in all patients, regardless of the different
      stratifications in their BL CD4 counts. Of note, the ENF-induced increase in CD4
      occurred significantly in all patients, independently of their BL IgE levels. The
      immunological response associated with ENF treatment is accompanied by a
      selective increase in IgE levels. Determination of IgE could be used in the
      monitoring ISRs associated with ENE

PMID- 17201089
TI  - Early evidence of lymphoproliferative disorder: post-transplant monitoring of
      Epstein-Barr infection in adult and pediatric patients.
AB  - Transplant patients are at high risk of post-transplant lymphoproliferative
      disorder (PTLD). A strong correlation between Epstein-Barr virus (EBV) and PTLD
      is observed in pediatric patients with primary infection after transplant.
      Because many patients have responded to reversal of immunosuppressive therapy, an
      early identification of EBV is essential for the reduction of immunosuppression
      and/or introduction of antiviral therapy to prevent PTLD. Polymerase chain
      reaction (PCR) is a specific and sensitive method to identify EBV DNA in blood.
      The aim of our study was to establish a protocol for monitoring EBV infection in
      transplanted patients for early identification those at high risk of PTLD. Viral
      presence in peripheral blood leukocytes (PBL) and serum samples was revealed by
      Nested PCR; positive specimens were quantified with Real Time PCR (RT-PCR). DNA
      in PBL was observed in 12 cases and 6 showed EBV in sera. Quantitative analysis
      showed a wide range of EBV DNA copies in leukocytes that were higher than in
      sera. Two patients displayed high viral load values in both PBL and sera
      associated with clinical evidence of PTLD. Our data suggest that the study of the
      EBV load represents an essential approach in the diagnosis of PTLD and the
      analysis of serum samples could provide useful information in the post-transplant
      monitoring of high-risk patients.

PMID- 17201091
TI  - Plasmid profiles and randomly amplified polymorphic DNA analysis of Salmonella
      enterica serotype Enteritidis strains from outbreaks and sporadic cases in
      Turkey.
AB  - The aim of the study was to investigate the characteristics of Salmonella
      serotype Enteritidis strains isolated from outbreaks and sporadic cases in Turkey
      by plasmid profiles and randomly amplified polymorphic DNA (RAPD) patterns. A
      total of 64 S. Enteritidis clinical strains were selected from the culture
      collection of the Enterobacteria Laboratory of Ankara University Medical School
      Department of Microbiology and Clinical Microbiology for molecular analysis using
      the plasmid profiles and RAPD method. Fifty-six isolates (88%) harbored one to
      four plasmids ranging in size from 2.5 to 100 kbp. 57 kbp plasmids were the most
      common plasmids, and forty-four strains (69%) carried 57 kbp plasmids alone or
      together with other plasmids. The outbreak strains carried the same plasmid
      profile: three plasmids sized 57, 40, 3.0 kbp. None of the strains analyzed
      displayed any RAPD bands with the primer OPB-17. By using primer p-1254, 42
      strains (66%) were divided into fourteen RAPD patterns. Ten of the outbreak
      strains (77%) showed >80% similarity by cluster analysis program. Analysis of
      RAPD-PCR with primer p-1254 proved an easy, rapid and discriminative method
      complementing antibiogram and plasmid profiles in routine laboratories, and may
      contribute to the investigations of S. Enteritidis which still cause outbreaks in
      Turkey. This study presents the first report on S. Enteritidis isolates in Turkey
      investigated by plasmid profiles and RAPD methods.

PMID- 17201090
TI  - A comparative evaluation between real time Roche COBas TAQMAN 48 HCV and bDNA
      Bayer Versant HCV 3.0.
AB  - The HCV virus is a common human pathogen made of a single stranded RNA genome
      with 9600nt. This work compared two different commercial methods used for HCV
      viral load, the bDNA Bayer Versant HCV 3.0 and the RealTime Roche COBAS TaqMan 48
      HCV. We compared the reproducibility and linearity of the two methods. Seventy
      five plasma samples with genotypes 1 to 4, which represent the population (45%
      genotype 1; 24% genotype 2; 13% genotype 3; 18% genotype 4) were directly
      processed with the Versanto method based upon signal amplification; the same
      samples were first extracted (COBAS Ampliprep - TNAI) and then amplified using
      RealTime PCR (COBAS TaqMan 48). The results obtained indicate the same
      performance for both methods if they have genotype 1, but in samples with
      genotypes 2, 3 and 4 the RealTime PCR Roche method gave an underestimation in
      respect to the Bayer bDNA assay.

PMID- 17201092
TI  - Growth of Salmonella enterica in model mixed cultures during a two-step
      enrichment.
AB  - Growth of Salmonella enterica was studied in model mixed cultures with
      Citrobacter freundii or Escherichia coli in buffered peptone water (BPW) and in
      Rappaport-Vassiliadis medium with soya (RVS) with modified concentrations of
      MgCl2 and malachite green, and at modified incubation temperatures. Selected S.
      enterica strains were inoculated in BPW (10(0) cfu/ml) together with selected
      strains of Citrobacter freundii (up to 10(8) cfu/ml) or selected strains of
      Escherichia coli (up to 10(8) cfu/ml), incubated overnight and then subcultured
      (1: 100) in RVS variants. Growth of individual bacterial species was followed by
      the quantitative real-time polymerase chain reaction (PCR). Optimal culture
      conditions during the second selective step were: MgCl2.6 H2O concentration of 29
      g/l, malachite green concentration of 36 mg/1l, and the incubation temperature of
      41.5 degrees C. Citr. freundii was found to be a potent competitor and E. coli
      was a weaker competitor. At optimal culture conditions, competition was reduced
      and the density of S. enterica cultures reached the level of 10(4) cfu/ml after
      not later than 2 h of selective enrichment. The results obtained provide a basis
      for the development of a short two-step enrichment to be used in rapid real-time
      PCR-based methods for the detection of S. enterica in food and other matrices.

PMID- 17201093
TI  - Evaluation of Cobas Amplicor MTB test to detect Mycobacterium tuberculosis in
      pulmonary and extrapulmonary specimens.
AB  - Tuberculosis (TB) is one of the major public health problems in the world.
      Effective control of TB depends on rapid and correct diagnosis and appropriate
      treatment. The aim of this study was to evaluate the performance of Cobas
      Amplicor MTB (CA-MTB) test for pulmonary and extrapulmonary specimens isolated in
      our laboratory. A total of 424 specimens obtained from the suspected TB patients
      from January 2003 to August 2004 were included in this study. All specimens (173
      pulmonary and 251 extrapulmonary specimens) were processed, stained, cultured and
      assayed using the CA-MTB test for identification of Mycobacterium tuberculosis.
      The CA-MTB test results were compared to culture and acid-fast staining as gold
      standard. The sensitivity, specificity, positive and negative predictive values
      of CA-MTB were determined as 73%, 100%, 100%, and 97% for pulmonary specimens,
      and 45%, 100%, 100% and 96% for extrapulmonary specimens respectively. The
      sensitivity of the test for acid-fast bacilli (AFB) smear positive pulmonary and
      extrapulmonary specimens was 92% and 75%. These results indicate that the CA-MTB
      is a rapid test for detection of tuberculosis in pulmonary specimens, but does
      not perform well enough in extrapulmonary specimens.

PMID- 17201094
TI  - In vitro efficacy of Linezolid on clinical strains of Mycobacterium tuberculosis
      and other mycobacteria.
AB  - Linezolid, an oxazolidinone that acts by inhibiting protein synthesis, was
      evaluated in strains of tuberculosis and non-tubercular mycobacteria resistant to
      one or more drugs isolated in northern Sardinia. The in vitro activity of
      Linezolid (Pfizer) was assessed on different isolates of Mycobacterium spp. from
      clinical samples by the Proportional Method. Linezolid demonstrated an excellent
      activity against the 24 strains of M. tuberculosis and against M. gordonae, M.
      marinum, M. aurum, M. phlei, and M. avium, with MIC values ranging from 0.5 to 2
      microg/ml. Linezolid can be used in combination with the standard antitubercular
      medications, or as an effective therapeutic alternative in infections caused by
      M. tuberculosis or by other species of non-tubercular mycobacteria.

PMID- 17201095
TI  - Identification and antibiotic susceptibility of bacterial isolates from probiotic
      products available in Italy.
AB  - This study was carried out to assay the bacterial viability and the probable
      contamination of a range of probiotic products available in Italy and to test the
      susceptibility of the isolates. Eleven dried food supplements and five fermented
      functional foods were examined using different isolation media under standardized
      cultivation conditions. The identification was made by conventional phenotypic
      characteristics and biochemical tests. Among isolates from the probiotic products
      antibiotic susceptibility was detected using the E-test (ABBiodisk). Our results
      demonstrate that nine food supplements and two fermented foods claimed species
      which could not be isolated, whereas potential pathogens (i.e. Micromonas micros)
      were isolated. Lactobacilli displayed species-dependent antibiotic resistance.
      Atypical resistance occurred for penicillin in Lactobacillus acidophilus and
      Lactobacillus bulgaricus and for erythromycin in Lactobacillus lactis and
      Lactobacillus salivarius. A broad range of MICs was observed for cephalosporins
      and fluroquinolones. Aminoglycosides had poor activity against Lactobacillus
      isolates. Two of the four isolates of Bifidobacterium exhibited high resistance
      to trimethroprim/sulfametoxazole and to fluoroquinolones. Our results suggest
      that some probiotic products claim species that cannot always be isolated, and
      are sometimes contaminated by potential pathogens. Moreover, the probable
      transferable erythromycin or penicillin resistance among the lactobacilli
      isolated should be taken into account.

PMID- 17201097
TI  - Chlamydophila pneumoniae in horses: a seroepidemiological survey in Italy.
AB  - We tested 731 sera from apparently healthy light horses against Chlamydophila
      pneumoniae, by a microimmuno-fluorescence (MIF) test. To verify cross-reactions
      with other species of chlamvdiae, all sera with an antibody titre > or = 32 to C.
      pneumoniae were tested against both C. psittaci and C. abortus. Antibodies to C.
      pneumoniae were detected in 194 out of 731 (26.5%) samples tested, with antibody
      titres ranging from 32 to 1024. No antibody titre > or = 32 was detected in sera
      to C. abortus. Only few sera with a high antibody titre to C. pneumoniae reacted
      weakly with C. psittaci at the dilution of 1:32.

PMID- 17201096
TI  - Differences in microbiological composition of saliva and dental plaque in
      subjects with different drinking habits.
AB  - Several foods have been shown to contain natural components (especially
      polyphenols) which display anti-adhesive properties against Streptococcus mutans,
      the aetiological agent responsible for dental crown caries, as well as inhibition
      of glucosyltransferases, which are the S. mutans enzymes involved in the
      synthesis of an adherent, water-insoluble glucan from sucrose. Other studies have
      demonstrated an in vitro action on oral plaque biofilm formation and desorption.
      This study evaluated whether the activity displayed in vitro by food compounds
      could affect the microbiological composition of saliva and dental plaque of
      subjects with a diet rich in these foods, comparing the results with those
      obtained from subjects with a different diet. The foods considered were: coffee,
      barley coffee, tea and wine. A total of 93 subjects were recruited into the
      study. Six samples of both plaque and saliva were collected from each subject at
      roughly one-monthly intervals. Total bacteria, total streptococci, S. mutans and
      lactobacilli counts were determined by culture in both saliva and dental plaque.
      The highest bacterial titres were recorded for the control population, while each
      drinking habit subgroup showed counts roughly one log lower than the controls.
      These differences in bacterial counts proved statistically significant (P<0.05).
      As far as dental plaque was concerned, while total counts did not significantly
      vary per mg of plaque in the subjects belonging to the different drinking habit
      subgroups, a significant decrease (P<0.05) was observed in those subjects
      drinking coffee, tea, barley coffee and wine when mutans streptococci and
      lactobacilli were evaluated. In several cases a more than one log decrease was
      observed. Plaque indices were also determined, and a significant (P<0.05)
      reduction in values was recorded in the subjects belonging the specific drinking
      habit subgroups compared to the control group. This study indicates that there is
      a correlation between consumption of specific foods and oral health in terms of
      reduced plaque deposition and lower counts of odontopathogens.

PMID- 17201099
TI  - Power and client-centred practice: an insider exploration of occupational
      therapists' experiences.
AB  - BACKGROUND: Although problems with power sharing are frequently described in
      discussions about client-centred practice, little research has explored
      occupational therapists' experiences with this model of service delivery. To
      critically examine this aspect of occupational therapy, an insider study was
      conducted. PURPOSE: The objectives of the study were to explore therapists'
      experiences with client-centred practice and to reveal how power works within
      this practice and in the health service environment. METHOD: Semi-structured
      interviews with 9 therapists were conducted, and a thematic analysis of these
      transcripts was completed. A variety of institutional documents were reviewed and
      analysed. RESULTS: Three main themes were identified: the different
      interpretations of occupational therapy discourse, the power of context, and the
      continuum of client-therapist interactions. CLINICAL IMPLICATIONS: It is
      important to consider the various competing discourses and institutional
      practices that frame the therapeutic relationship when evaluating methods to
      improve client-centred practice.

PMID- 17201098
TI  - Molecular study of genes involved in virulence regulatory pathways in Bacillus
      anthracis vaccine strain "Carbosap".
AB  - This study investigated the genetic bases of attenuation in the Bacillus
      anthracis vaccine strain "Carbosap" used in Italy against anthrax in cattle and
      sheep. Twelve genes involved in virulence regulatory pathways underwent sequence
      analysis in comparison with a B. anthracis virulent strain.

PMID- 17201100
TI  - Health education for people with macular degeneration: learning experiences and
      the effect on daily occupations.
AB  - BACKGROUND: Discovering New Ways, a program for people with macular degeneration,
      was developed based on a health education model incorporating occupation.
      PURPOSE: The purpose of this study was to evaluate the participants' learning
      experience in the program and the significance for their daily occupations.
      METHOD: Within an experimental design format, a content analysis was performed.
      Ninety-two people with macular degeneration were interviewed 1 and 16 months
      after the intervention. RESULTS: Participants in the individual intervention
      program stated that they mastered occupational tasks as a result of the provision
      of assistive devices. Participants in the health education program stated that
      the problem-solving toolbox provided them with hope and confidence to master
      daily occupations. The participants'experience of learning within the health
      education program has provided important feedback regarding the structure of the
      health education model and its learning process. PRACTICE IMPLICATIONS: The
      health education model may be seen as a model to design early interventions for
      individuals with health conditions which can impact occupational performance.

PMID- 17201101
TI  - [The importance of playfulness in occupational therapy with adult clients].
AB  - BACKGROUND: As there is little documentation pertaining to playfulness in adults,
      its therapeutic potential remains uncertain. PURPOSE AND METHODOLOGY: A
      qualitative approach was used in order to develop a conceptual model of
      playfulness in adults and to discuss its potential uses in occupational therapy.
      RESULTS: The model identifies the influential sources and the consequences of
      playfulness in adults. The identified consequences support both the privileged
      intervention in occupational therapy, in other words, the meaningful activity,
      and the objectives of the intervention, those which include being the capacity to
      act, health and well-being. For these reasons, the proposed model presents
      interesting potential for occupational therapy intervention. CLINICAL
      IMPLICATIONS: This conceptual model presents a unique and innovative vision of
      playfulness in adults that could offer a new perspective on meaningful activity.
      It suggests that playfulness could become an important tool in occupational
      therapy in developing the capacity to act. Consequently, the model proposes an
      innovative client-based approach.

PMID- 17201102
TI  - Critical elements of spirituality as identified by adolescent mental health
      clients.
AB  - BACKGROUND: Client spirituality has been recognized as a central component of
      Canadian occupational therapy, but little research has been conducted in this
      area. PURPOSE: This exploratory study attempted to gain insight into the relevant
      elements of spirituality and its importance to inpatient adolescent mental health
      clients. METHOD: An adolescent spirituality questionnaire was developed from
      definitions of spirituality in the literature, modified by a focus group
      consisting of members of the target population, and administered to 11
      respondents. RESULTS: Elements related to the individual and lifelong pursuits of
      the individual were most closely associated with spirituality while those items
      traditionally connected with spirituality and with external pursuits, activities,
      and relationships are considered less relevant by this population. Results
      suggest that spirituality is important to a majority of inpatient adolescent
      mental health clients. PRACTICE IMPLICATIONS: It is suggested that more studies
      drawing information on spirituality directly from specific client populations are
      essential for the occupational therapy community to improve its comprehension of,
      and to better its ability to address in practice, the critical area of client
      spirituality.

PMID- 17201103
TI  - Discharge planning with older adults: toward a negotiated model of decision
      making.
AB  - BACKGROUND: Occupational therapists are frequently involved in discharge
      accommodation decision making with older adults. PURPOSE: The literature
      regarding this process is reviewed. The ways in which risk avoidance and autonomy
      promotion philosophies influence decisions are examined and a new approach is
      proposed. SUMMARY: One approach is based on risk avoidance, where decisional
      control rests with professionals, but the client is left out of the process.
      Another is that of autonomy promotion, in which decisional control rests with the
      client. When risks are high, this can result in ethical dilemmas. The importance
      of the environment, its relationship to occupational performance, and differing
      interpretations of client-centred processes are important considerations.
      PRACTICE IMPLICATIONS: In response to the inadequacy of models grounded in risk
      avoidance or autonomy promotion, occupational therapists are challenged to move
      toward a balanced approach to decision making with older people, grounded in
      partnership, shared power, and negotiation.

PMID- 17201104
TI  - [Medical ethics and pharmaceutical industry's practices (editorial)].

PMID- 17201105
TI  - [Neuroendocrine differentiation and markers of cell proliferation in a group of
      patients with prostate adenocarcinoma and normal or high serum prostate-specific
      antigen levels].
AB  - OBJECTIVE: Study the morphologic characteristics of neuroendocrine cells in
      prostate cancer with normal versus elevated prostate specific antigen (PSA).
      MATERIALS AND METHODS: 372 cases of prostate cancer were identified during a 13
      year period, of which 19 displayed normal PSA (group I). Sixteen controls with
      elevated PSA and similar histopathological characteristics (group II) were
      included. We studied the degree of tumor necrosis, vascular and perineural
      invasion. Synaptophysin (SP), neuron specific enolase (NSE), PSA, Ki-67 and p53
      inmunoreactivity were also analyzed. RESULTS: Group I positive findings were 61%
      PSA, 28.6% SP. 7.1% NSE, 50%p53, and 78.6% Ki-67. Group II positive findings were
      93% PSA, 13.3% SP, 26.6% NSE 46.6% p53, and 66.7% Ki-67. When we used a <80% cut
      off point for PSA immunoreactivity in tumor cells, 69.2% of group I and 21.4% of
      group II were found. CONCLUSIONS: The sole histopathological finding that showed
      statistical significance was the tissular expression of the specific prostatic
      antigen in 80% of neoplasic cells in group I. The increase of neuroendocrine
      cells was associated with a smaller number of tissular antigen producing cells, a
      finding that could be more apparent if we were to study a larger sample size.

PMID- 17201106
TI  - [Prevalence of hepatitis B virus infection in patients suffering from acute and
      chronic liver disease in three public hospitals in Durango, Mexico].
AB  - OBJECTIVE: We carried out an observational, descriptive, and retrospective
      epidemiological study in order to determine the prevalence of hepatitis B virus
      infection (HBV) in patients with acute and chronic liver disease in three public
      hospitals of Durango, Mexico. MATERIAL AND METHODS: Sixty five adult patients
      were included in the study. Fifty eight (89%) were inpatients and 7 were
      outpatients. Twenty three patients suffered from acute hepatitis, 10 chronic
      hepatitis, 29 liver cirrhosis, 2 hepatocellular carcinoma, and I fulminant
      hepatitis. A questionnaire was administered to all participants that included
      sociodemographic and epidemiological data. In addition, serum samples were
      analyzed for hepatitis B surface antigen (HBsAg) by an immunoassay (A UZYME
      Monoclonal), manufactured by ABBOTT Diagnostics (North Chicago, IL, USA).
      RESULTS: Out of the 65 patients, 2 (3%) were positive for HBsAg. Of the two
      positive cases, one had chronic hepatitis and other liver cirrhosis. Both
      positive cases had histories of blood transfusion, surgery, and alcohol abuse. In
      addition, one of them had a history of acupuncture. Previous traveling (within
      Mexico, abroad or both) was more frequently observed in HBsAg positive patients
      than in HBsAg negative patients (p <0.05). CONCLUSION: We concluded that the
      prevalence of HBV infection in patients with liver disease in the city of Durango
      is low. This prevalence is comparable or lower than the one reported in other
      Mexican cities, and lower than other countries.

PMID- 17201107
TI  - [Knowledge and attitudes of Mexican population concerning solar radiation].
AB  - BACKGROUND: The effects of solar radiation in human health is dependent upon
      environment, behavior, and genetic characteristics. OBJECTIVE: Identify
      phenotypic features, attitudes, knowledge and preventive measures concerning sun
      exposure among a local population. METHODS: People older than 15 years were
      interviewed concerning time of sun exposure, photoprotection, and general
      knowledge about adverse effects of sun irradiation. RESULTS: 964 questionnaires
      were analyzed. White-skin population represented 7.4%, light-brown 24.8%, dark
      brown 67.8%. Exposure time on working days was up to 15 min in 27.8%, and more
      than 60 min in 38.8%. On weekends, time exposure was similar. 30% did not take
      any preventive measures 41% wore hats and 11.8% used sunscreens. Among
      participants, 85.4% were aware that sun exposure caused skin cancer, 64. 1% knew
      that mortality is increased, 83.4% reported that excessive sun exposure is
      related to aging of the skin, and 26.5% believed tanning is healthy. CONCLUSIONS:
      In spite of thefact that a great majority of the population recognized that sun
      exposure produces aging and skin cancer, their exposure is widespread. This
      survey may be a valuable tool to design preventive public health campaigns that
      target high risk groups.

PMID- 17201108
TI  - [Utility of conceptual schemes and mental maps on the teaching-learning process
      of residents in pediatrics].
AB  - BACKGROUND: The present study was done at the internal medicine service oft he
      Hospital lnfantil in the State of Sonora, Mexico. We tried to address the
      question of the use of conceptual schemes and mind maps and its impact on the
      teaching-learning-evaluation process among medical residents. OBJECTIVE: Analyze
      the effects of conceptual schemes, and mind maps as a teaching and evaluation
      tool and compare them with multiple choice exams among Pediatric residents.
      MATERIAL AND METHODS: Twenty two residents (RI, RII, RIII)on service rotation
      during six months were assessed initially, followed by a lecture on a medical
      subject. Conceptual schemes and mind maps were then introduced as a teaching
      learning-evaluation instrument. Comprehension impact and comparison with a
      standard multiple choice evaluation was done. The statistical package (JMP
      version 5, SAS inst. 2004) was used. RESULTS: We noted that when we used
      conceptual schemes and mind mapping, learning improvement was noticeable among
      the three groups of residents (P < 0.001) and constitutes a better evaluation
      tool when compared with multiple choice exams (P < 0.0005). CONCLUSION: Based on
      our experience we recommend the use of this educational technique for medical
      residents in training.

PMID- 17201109
TI  - [Intersection between gender and socioeconomic status in medical sciences career
      choice].
AB  - OBJECTIVE: Analyze the relationship between gender identity and socioeconomic
      level associated with career choice among undergraduate students selecting the
      area of health sciences. MATERIAL AND METHODS: Our sample was comprised of first
      year medical nutrition, dentistry and nursing students (n=637) admitted to the
      Universidad Autonoma Metropolitana - Xochimilco. A self administered
      questionnaire was used. The dependent variable was career choice. Independent
      variables included socioeconomic status, gender norms in student's homes, and
      gender stereotype internalization. RESULTS: More female nursing students came
      from low socioeconomic strata, while medical students had a higher socioeconomic
      status. Among males, more nursing and medical students belonged to a higher
      socioeconomicstrata. Nutrition and dentistry students belonged to a medium
      strata. In comparison with males from high socioeconomic strata more male
      participants reported that household chores were divided among men and women. For
      women, as the socioeconomic level increased, the participation of men and women
      also increased. In the indicators of internalization of gender stereotypes,
      nursing students had the highest rates in the submission scale, but the lowest
      for masculinity and machismo. As the socioeconomic strata increased, the
      characteristics of masculinity and machismo also increased. CONCLUSIONS: The
      present results seem to indicate that among women of low socioeconomic strata
      more traditional gender stereotypes prevail which lead them to seek career
      choices considered femenine. Among men, there is a clear relationship between
      career choice, socioeconomic level and internalization of gender stereotypes.

PMID- 17201110
TI  - [Diagnosis of Wegener's granulomatosis in patients with ocular inflamatory
      disease].
AB  - OBJECTIVE: Report the ophthalmologic manifestations among patients with Wegener
      's Granulomatosis (WG). METHOD: We reviewed the database of the Instituto de
      Oftalmologia Fundacion Conde de Valenciana in order to collect information
      regarding complete ophthalmic examination, laboratory and cabinet tests,
      treatment, and disease progression. RESULTS: We included 11 patients with WG (18
      eyes). Seven men and four women, mean age 43.7 years (range = 28-55). Three
      patients had a prior diagnosis of WG and the remaining eight patients were
      diagnosed by our study team. Seven subjects developed a bilateral affection and
      four had unilateral involvement. The clinical presentation was necrotizing
      scleritis with peripheral ulcerative keratitis (PUK) (7/18), diffuse scleritis
      (3/18), nodular scleritis (1/18), non-granulomatous uveitis (1/18), optic
      ischemic neuropathy (1/18), retrobulbar neuritis (1/18), serous retinal
      detachment (2/18), and dacryocystitis (2/18). Final visual acuity was better or
      equal to 20/40 (13/18), 20/400 (3/18), finger-counting or no-perception of light
      in 1/18. Currently, seven patients are symptom free. CONCLUSIONS: The most
      frequent ophthalmic manifestations among our patients with WG were: necrotizing
      scleritis and PUK. In most cases, WG was diagnosed after ophthalmic
      manifestations; however, all patients displayed prior systemic or ocular
      symptoms.

PMID- 17201111
TI  - [Exenatide: use in humans].
AB  - Exenatide is the first synthetic agonist of the GLP-1 (glucagon-like peptide 1)
      receptor approved for clinical use in patients with type 2 diabetes. The
      multiplicity of its effects over glucose metabolism, appetite, body weight and
      its potential capacity to preserve the ?cell mass, makes it an attractive
      therapeutic alternative. This article attempts to review the current literature
      on pharmacokinetics, pharmacodynamics, efficacy, and safety of exenatide in
      humans, derived from the early phase I and II studies, and from the clinical
      controlled trials that led to its approval for clinical use as a combination
      therapy with sulphonylureas and metformin.

PMID- 17201112
TI  - [West Nile virus: a reality in Mexico].
AB  - West Nile virus (WNV) is a RNA virus of the Flaviridae, genus flavivirus family.
      It is a neuropathogenic virus causing disease in birds, horses and humans. WNVis
      transmitted by the vector mosquito Culex sp. The virus life 's cycle includes
      mosquitoes as vectors and birds as natural hosts. Humans are accidental hosts.
      Since the introduction of the Epidemiological Surveillance Program at the
      Ministry ofHealth. we have documented 90 positive test results among birds out of
      1,223 cases studied in Mexico as of September IS. 2005. The incubation period in
      humans after a mosquito bite ranges from 3 to 14 days. Disease is characterized
      by early onset fever, general malaise, decreased appetite, nausea, vomiting,
      headaches, myalgias, enlarged lymph nodes andrash. Neurological manifestations
      include encephalitis andflaccid paralysis, which are present in less than 1% of
      subjects infected with WNV. Older patients display more adverse outcomes
      including death. The diagnosis is made by the determination of specific IgM and
      JgG antibodies in serum and/or cerebrospinal fluid. There is no antiviral
      treatment to date against WNV but interferon ?2b, and WNVspec4ic-immunoglobulin
      have been used Prevention is therefore the key to control the infection.

PMID- 17201113
TI  - [A 54 year old woman with heartbeats, blurred vision, mental confusion, and
      hypoglycemia].

PMID- 17201114
TI  - [Crusted scabies (Norwegian scabies) a case report].
AB  - Different types of scabies have been described based on their clinical outcome,
      one of which is the Crusted (Norwegian) type. This is an extreme manifestation of
      scabies that can be observed mainly among immunosupressed patients. A case ofa 42
      year-old homosexual man is described. The patient was diagnosed with HIV,
      presenting pruritic lesions with a 4 month evolution in trunk and extremities.
      Lesions included xerosis, decapitated papules, badges with erythema, residual
      hyperchromic stains, multiple abrasions and ungueal pigmentation in both feet. At
      the beginning it was treated as apsorasiform dermatitis with steroids and
      antipruritics without success. Through a biopsy the suspected diagnosis of
      Crusted (Norwegian) scabies was confirmed. The patient was treated with a dose of
      oral ivermectin and topical benzyl benzoate and showed remission after two days.

PMID- 17201115
TI  - [Isolated renal mucormicosis].
AB  - Mucormycosis is an infection caused by a class Zygomycetes fungi. The
      rhinocerebral and pulmonary are the most common clinical presentations. Renal
      mucormycosis is a very rare form. To date, only 25 cases have been reported in
      the literature. We describe the case of a patient with leukemia who developed
      isolated renal mucormycosis and review the literature.

PMID- 17201116
TI  - [Bilateral dorsal elastofibroma].

PMID- 17201117
TI  - [Genomics in Down syndrome].

PMID- 17201118
TI  - [Goethe's philosophical-medical masks, in Faust].
AB  - At the beginning of the XXI century the health profession is engaged in a medical
      ethical and moral crisis and society, hurt by the pandemic of violence and
      impunity, feels the effect of a state of legal crisis unable to find a viable
      scientific or humanistic answer. This manuscript, is the result of an
      investigation into the Johann Wolfgang Goethe's tragedy of the nineteenth
      century, Faust. It demonstrates the coincidence of real life subjects and objects
      with literary subjects and objects represented, by means of the interpretation of
      the paradigms, problems, dilemmas and identified cases of medical ethical-morals:
      daimon, reflection-solitude, free will, good-evil, Eros, learned ignorance,
      genes, epistemology, medical etiquette, paternalism, anatomy of the personality,
      Hyppocratism, will, good sense of humor, bubonic plague. Faust can be construed
      as a new path for change--towards the common good--of the physician if traced by
      their will and recovering the represented real objects, decides to meditate free
      and lonely on its professional exercise, medical knowledge and the doctor-patient
      relationship.

PMID- 17201119
TI  - Analysis of a mutant p53 protein arising in a medulloblastoma from a mouse
      transgenic for the JC virus early region.
AB  - BACKGROUND: JC virus (JCV) is a polyomavirus that causes progressive multifocal
      leukoencephalopathy (PML) in humans and is highly oncogenic in experimental
      animals. Transgenic mice with JCV T-antigen develop cerebellar tumors, which
      resemble human medulloblastomas, containing two distinct cell subpopulations, T
      antigen positive and negative. In T-negative clones, a novel mutant p53 was
      detected (p53(mt)). MATERIALS AND METHODS: We have compared p53(mt) to wild-type
      p53 (p53wt) in p53-null cells. RESULTS: p53(mt) had lost the transcriptional
      transactivation activity of p53(wt), and unlike p53(wt), partially localized to
      the cytoplasm. Unlike mutant p53 from many human cancers, p53(mt) did not show a
      gain of function or a dominant negative phenotype. Adenovirus expressing p53(wt)
      but not p53(mt) inhibited cell growth and induced apoptosis of p53-null cells.
      CONCLUSION: During the course of tumor evolution of the JCV T-antigen mouse
      medulloblastoma, a mutation occurred that inactivated p53 allowing tumor
      progression even in the absence of continued T-antigen expression.

PMID- 17201120
TI  - Endogenous expression of CD80 co-stimulatory molecule facilitates in vivo tumor
      regression of oral squamous carcinoma.
AB  - BACKGROUND: Most tumor tissues, especially those of non-hematopoietic origin, do
      not express CD80 co-stimulatory molecules, possibly as a mechanism to evade
      immune surveillance. The objective of this study was to determine whether
      abundant endogenous CD80 expression on oral squamous cell carcinoma (SCC) early
      during tumor progression can facilitate immune elimination and reverse immune
      tolerance. MATERIALS AND METHODS: The growth of regressor and progressor oral SCC
      lines with differing endogenous CD80 expression were examined in immune-competent
      and -deficient mice. Immune effectors were determined by T-cell depletion
      experiments and immunohistochemistry. RESULTS: Our studies show regression of
      early tumor growth when immunocompetent animals are inoculated with oral SCC
      progressor cell lines expressing abundant endogenous CD80. The CD80-induced
      antitumor response was due largely to induced T-cell responses. CONCLUSION: Our
      findings suggest that inadequate CD80 expression during early oral SCC formation
      may contribute to the escape of tumors from immune elimination. This information
      can be useful in the design of new approaches to generate more effective
      immunotherapy against this disease.

PMID- 17201121
TI  - COX-independent antineoplastic effects of sulindac in oral cancer are mediated by
      survivin down-regulation.
AB  - BACKGROUND: Cyclooxygenase (COX) inhibitors are reported to exert anti
      proliferative and pro-apoptotic effects on cancer. The effects of COX inhibitors
      on oral squamous cell carcinoma (SCC) and survivin expression were assessed.
      MATERIALS AND METHODS: Primary oral SCC were analyzed immunohistochemically, and
      oral SCC cell lines were assessed using RT-PCR, Western blot, cell proliferation
      and apoptosis assays, following treatment with various COX inhibitors, SiRNA
      against survivin, or survivin forced expression. RESULTS: Survivin was expressed
      in all studied tumors. SiRNA against survivin or treatment with sulindac, but not
      other COX inhibitors, decreased survivin expression and tumor cell proliferation
      and increased apoptosis. Forced expression of survivin attenuated sulindac's
      effects. CONCLUSION: Survivin is implicated as a marker and treatment target in
      oral SCC, inhibition of which causes reduction of cell proliferation and
      induction of apoptosis. Down-regulation of survivin expression by sulindac
      provides an explanation for its antineoplastic effects.

PMID- 17201123
TI  - Identification and evaluation of potential anti-cancer drugs on human
      neuroendocrine tumor cell lines.
AB  - The aim of this study was to investigate drug sensitivity in neuroendocrine tumor
      cell lines. MATERIALS AND METHODS: In vitro drug sensitivity screening was
      performed using the fluorometric microculture cytotoxicity assay in one human
      pancreatic carcinoid and two human bronchial carcinoid cell lines. In addition, a
      normal human retinal pigment epithelial cell line was used for comparison. A
      total of 18 drugs with different mechanisms of action were tested. RESULTS: The
      most active agents were brefeldin A, emetine, bortezomib and idarubicin, having
      IC5o values <1 microM in all four cell lines. In addition, the three tumor cell
      lines showed sensitivity for sanguinarine, Bayll-7085, mitoxantrone, doxorubicin,
      beta-lapachone, NSC 95397 and CGP-74514A. CONCLUSION: The cell lines were
      sensitive for several drugs acting in different ways, covering a broad spectrum
      of mechanisms of action. Some of these compounds may possibly be used in clinical
      trials and show therapeutic effect in patients with neuroendocrine tumors.

PMID- 17201122
TI  - TRAIL expression up-regulated by interferon-gamma via phosphorylation of STAT1
      induces myeloma cell death.
AB  - BACKGROUND: Although the cellular and molecular biological effects of interferon
      (IFN)-alpha have been well-investigated, the effects of IFN-gamma are less
      understood. MATERIALS AND METHODS: Eleven human myeloma cell lines with various
      myeloma-specific chromosomal translocations and overexpression of oncogenes were
      cultured with 1000 U/ml of IFN-gamma. In the KMS-20 cells, which showed growth
      inhibition due to IFN-gamma, trail expression, status of the Janus kinase
      (JAK)/STAT pathway were analyzed. RESULTS: KMS-20 cells showed marked up
      regulation of trail, activation of STAT1 and TRAIL hyperproduction induced by IFN
      gamma. CONCLUSION: The effects of IFN-gamma on growth inhibition of KMS-20 cells
      were characterized by activation of the JAK/STAT signalling pathway, particularly
      STAT1 phosphorylation, enhanced secretion of TRAIL, and auto/paracrine usage of
      secreted TRAIL to induce apoptotic cell death. From these results, IFN-gamma may
      be considered one of the drugs to be used in future multidrug chemotherapeutic
      regimens for myeloma patients.

PMID- 17201124
TI  - Antitumor and antimetastatic activity of a novel water-soluble low molecular
      weight beta-1, 3-D-glucan (branch beta-1,6) isolated from Aureobasidium pullulans
      1A1 strain black yeast.
AB  - Though it has been reported that beta-glucans or protein-binding hetero-glucans
      isolated from mushrooms have antitumor activity, the antitumor and antimetastatic
      actions of purified, structurally defined polysaccharides (such as beta-glucans)
      have not been proven yet. A new low molecular weight (approximately 100 kDa) beta
      glucan was isolated from Aureobasidium pullulans black yeast, and was found to
      have low viscosity and to be water-soluble. The industrial production of this P
      glucan was achieved from the culture media of A. pullulans. The effects of water
      soluble low-molecular-weight (LMW) beta-(1-->3) and 50-80% branched beta-(1-->6)
      glucan isolated from A. pullulans on tumor growth and metastasis to the liver
      were examined in mice intrasplenically with implanted colon 26 tumor cells. In
      addition, to clarify the antitumor and antimetastatic actions of LMW beta-(1,3
      1,6) glucan, the effects on immune functions in the small intestine were also
      examined. The intraperitoneal (5 and 15 mg/kg) and oral (50 mg/kg) administration
      of LMW P-(1.3-1.6) glucan inhibited the tumor growth and liver metastasis in mice
      intrasplenically implanted with colon 26 cells. The numbers of natural killer
      (NK)- and interferon (IFN)-gamma-positive cells in the small intestine of colon
      26-bearing mice were lower than those in normal mice. The intraperitoneally and
      orally administered LMW beta-(1,3-1,6) glucan prevented the reduction of the
      number of NK- and IFN-gamma-positive cells induced by the tumor growth after
      implantation of colon 26 cells. These findings suggest that the antitumor and
      antimetastatic actions of LMW beta-(1,3-1,6) glucan may involve the enhancement
      of intestinal immune functions through increases in NK- and IFN-gamma-positive
      cell numbers.

PMID- 17201125
TI  - Atrial natriuretic peptide and long acting natriuretic peptide inhibit ERK 1/2 in
      prostate cancer cells.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) and long acting natriuretic peptide
      (LANP) have anticancer effects in human prostate adenocarcinomas. MATERIALS AND
      METHODS: ANP, LANP and cyclic GMP's effects on extracellular signal-regulated
      kinase (ERK) 1/2 kinase were examined in human prostate adenocarcinoma cells.
      RESULTS: ANP and LANP decreased the activation of ERK 1/2 over a concentration
      range of 0.01 microM to 10 microM. ANP and LANP's maximal inhibition of the
      phosphorylation of ERK 1/2 kinase were 94% and 88% (p < 0.0001), respectively.
      ANP had significant effects within five min at its 10 microM concentration. The
      inhibition of ERK 1/2 lasted for at least two h, where it was maximal, secondary
      to both peptides. Their ability to inhibit ERK 1/2 was inhibited by cyclic GMP
      antibody and cyclic GMP itself inhibited ERK 1/2 phosphorylation. CONCLUSION: ANP
      and LANP both inhibit ERK 1/2 kinase mediated via cyclic GMP as part of their
      anticancer mechanism(s) of action.

PMID- 17201126
TI  - Changes in nucleic acid and protein levels in atrophying skeletal muscle in
      cancer cachexia.
AB  - BACKGROUND: To investigate factors responsible for muscle loss in cachexia
      changes in nucleic acid and protein levels have been determined and compared with
      those induced by a tumour-produced cachectic factor, proteolysis-inducing factor
      (PIF). MATERIALS AND METHODS: Mice were transplanted with the MAC16 tumour, while
      non-tumour bearing mice received PIF (1.5 mg/kg; i.v.) over a 24 h period.
      RESULTS: There was an exponential decrease in RNA and protein in gastrocnemius
      muscle with weight loss without an effect on the DNA content. Levels of myosin
      followed the decrease in total protein, while actin levels remained constant.
      There was also a significant loss of protein from soleus muscle and spleen, but
      not from heart, liver and kidney. PIF also produced a significant loss of RNA and
      protein in spleen and reduced the protein content of soleus muscle. CONCLUSION:
      This suggests that PIF may be responsible for changes in protein and RNA content
      of tissues with the development of cachexia.

PMID- 17201127
TI  - The proliferative response of hela cells to 2-deoxy-D-glucose under hypoxic or
      anoxic conditions: an analogue for studying some properties of in vivo solid
      cancers.
AB  - BACKGROUND: Hypoxic cancer cells located beyond the diffusion path of sufficient
      oxygen are considered a nidus of therapeutic failure. Due to the dependence of
      many malignantly transformed cells on glycolysis for metabolic energy, inhibiting
      this and other sources of energy should seriously reduce cell viability and
      proliferation, additively or even synergistically. MATERIALS AND METHODS: To try
      and duplicate in vitro some of the features of in vivo cancer cells likely to
      resist therapy, HeLa cells were incubated with sub-lethal concentrations of 2
      deoxy-D-glucose under aerobic, hypoxic or virtually anoxic conditions, verified
      by increased synthesis of Hif-1alpha, and their replication and survival
      determined. MK 886, an inhibitor of mitochondrial function was used to estimate
      participation of that organelle in energy metabolism. RESULTS: Culture of
      cervical cancer-derived HeLa cells with 2-deoxy-D-glucose under these restrictive
      conditions did not reduce their proliferation or viability to the expected
      extent. Their surprisingly robust survival included the anticipated increase in
      dependence upon glycolysis and implied a likely entrainment of other constitutive
      and possibly facultative energy sources and pathways. Increased synthesis of Hif
      1alpha, increased binding to its consensus sequence and reduced inhibition from
      MK 886 in cells under oxygen-deficient environments confirmed the presence of
      restrictive conditions. CONCLUSION: Efforts to suppress HeLa cell survival by
      reducing glucose consumption and metabolic energy from ambient oxygen may require
      inhibition of multiple energy sources, possibly not all of them identified. In
      vitro assessment of agents directed against sources of metabolic energy or of
      other therapeutic agents against these or additional potential targets should
      include studies under hypoxia and relative anoxia. In this way, the possible
      responses of in vivo hypoxic or anoxic cancer cells believed to contribute to
      therapeutic failure may be estimated.

PMID- 17201128
TI  - Role of activation peptide of procathepsin D in proliferation and invasion of
      lung cancer cells.
AB  - BACKGROUND: Procathepsin D (pCD) secreted by cancer cells, increases
      proliferation, metastasis and progression of breast cancer, however its role in
      lung cancer is still unclear. The purified pCD and its synthetic activation
      peptide (AP) have shown similar proliferative effect on various cancer cell
      lines. The aim of this study is to clarify the role ofpCD and its AP in lung
      cancer by stable expression of pCD and pCD lacking its AP, in NCI-H23 lung cancer
      cells. MATERIALS AND METHODS: The stable transfected clones were tested for cell
      proliferation, invasion and growth in nude mice. The effect of exogenous addition
      of purified pCD and its mutant proteins was also analyzed by proliferation assay.
      RESULTS: The invasion and proliferation in vitro and tumor growth in vivo,
      demonstrated that the expression of pCD enhances the carcinogenic properties of
      NCI-H23 cells and that the AP is essential for these activities. Exogenous
      addition of purified proteins on various lung cancer cell lines showed that
      neither catalytic activity nor glycosylation are involved in the growth-promoting
      activity. CONCLUSION: This is the first report of pCD cDNA expression in lung
      cancer cells that enhances the growth and invasion of these cells both in vitro
      and in vivo.

PMID- 17201130
TI  - Evaluation of cancer chemopreventive agents using clones derived from a human
      prostate cancer cell line.
AB  - BACKGROUND: The successful use of clonal selection through fluctuation analysis
      of human cancer cells as a means for studying tumor progression has been
      previously reported. MATERIALS AND METHODS: Three clones derived from a parental
      population of human prostate cancer (LNCaP) cells were selected based on
      proliferation, hormone sensitivity and anchorage-independent growth. The effects
      of five potential cancer preventive agents were evaluated using cell
      proliferation, anchorage-independent growth and apoptosis as end-points. RESULTS:
      Clone 21 cells, which represent a presumptive normal phenotype, were generally
      more sensitive than Clone 17 and Clone 6 cells, which represent a more malignant
      phenotype, to fluasterone, 7beta-HF, L-selenomethionine and troglitazone in
      assays for proliferation and/or apoptosis. CONCLUSION: The results confirm the
      efficacy of the above agents as cancer chemopreventive agents and support our
      contention that clonal selection of established human cancer cells provides a
      model to study the efficacy of chemopreventive agents.

PMID- 17201129
TI  - Xenotransplantation of human ovarian tissue pieces in gonadotropin-stimulated
      SCID mice: the effect of ovariectomy.
AB  - The number of follicles were compared in different developmental stages after the
      cryopreservation of human ovarian tissue by open freezing system followed by
      xenotransplantation into severe combined immunodeficient (SCID)-mice under
      stimulation, with and without ovariectomy. Ovarian tissue, cryopreserved for
      fertility preservation was partly examined by LIVE/DEAD viability staining or was
      transplanted in the neck muscle of 32 SCID-mice. The development of follicles,
      estradiol production, vaginal cytology and uterus weight was assessed after 15
      weeks under gonadotropin stimulation, with or without ovariectomy. Viable
      follicles were detected in all frozen/thawed specimens using the LIVE/DEAD assay.
      Ovariectomy caused a significant improvement of survival of follicles in the
      preantral and antral stages in the gonadotropin-stimulated animals (p < 0.001),
      whereas there was no significant effect on the primordial and primary follicle
      counts. In the non-ovariectomised group, only isolated primordial and primary
      follicles could be detected. The total follicle amount was significantly higher
      in the ovariectomised group (n=17, 9.2 +/- 7.8, mean +/-SD) than in the non
      ovariectomized group (n=15, 0.3 +/- 1.0). This study demonstrates that
      ovariectomy of stimulated recipient SCID-mice is essential for the development of
      follicles after xenotransplantation of cryopreserved human ovarian grafts.

PMID- 17201131
TI  - Regulation of tumor signaling pathways by AZD3409 in vitro.
AB  - BACKGROUND: The antineoplastic activity of AZD3409 was evaluated in relation to
      paclitaxel in human breast (MDA-MB-231, BT-474) and ovarian (A2780, A2780cp)
      cancer cell lines. Biomarkers of apoptosis, protein prenylation, survival,
      angiogenesis and cellular growth were determined. MATERIALS AND METHODS:
      Cytotoxicity was evaluated by MTS assay, and apoptosis was evaluated by TUNEL.
      Biomarkers were measured by Western blots and ELISA. RESULTS: The IC50
      concentrations of AZD3409 in MDA-MB-231, BT-474, A2780 and A2780cp were 19.16,
      5.69, 3.19, and 8.86 microM, respectively. The corresponding apoptogenic EC50
      concentrations were 6.81, 4.15, 1.54 and 4.59 microM. CONCLUSION: Famesylation of
      HDJ-2 was inhibited in all cell lines. Secretion of VEGF, bFGF and MMP-1 were
      inhibited in the breast lines but augmented in the ovarian lines. AZD3409
      increased Akt activation in breast lines and decreased it in ovarian lines,
      without effect on MEK or ERK activation. AZD3409 cytotoxicity is mediated in part
      by inhibition of farnesylation.

PMID- 17201132
TI  - Uniform MDM2 overexpression in a panel of glioblastoma multiforme cell lines with
      divergent EGFR and p53 expression status.
AB  - BACKGROUND: Overexpression and deletion mutation of the epidermal growth factor
      receptor (EGFR) gene, as well as murine double minute 2 (MDM2) overexpression
      have been linked to the absence of p53 gene mutations in human glioblastoma
      multiforme (GBM). MATERIALS AND METHODS: EGFR and MDM2 messenger (m)RNA
      expression profiles and p53 status were examined by reverse transcription
      polymerase chain rection (RT-PCR) and gene sequencing, respectively, in a set of
      human wild-type (wt) p53 GBM cell lines (U-87MG, U-87MG.wtEGFR and U
      87MG.deltaEGFR) that exclusively differ in EGFR expression (endogenous wt EGFR
      expression, exogenous wt EGFR overexpression and exogenous 801-bp deletion-mutant
      [delta] EGFR overexpression, respectively), as well as in two human mutant p53
      GBM cell lines that differ approximately two-fold in endogenous wt EGFR mRNA
      expression. RESULTS: Regardless of the underlying heterogeneity in EGFR mRNA
      expression and p53 status, MDM2 was similarly overexpressed among the cell lines.
      CONCLUSION: These data suggest that in human GBM (i) overexpression of wt or
      deltaEGFR and of MDM2 may constitute independent genetic events, (ii)
      overexpression of wt EGFR and mutation of p53 in GBM, although considered
      mutually exclusive in vivo, are not reciprocally prohibitive per se, and (iii)
      p53 mutations do not necessarily preclude MDM2 overexpression. In addition, this
      set of human GBM cell lines may constitute a suitable model for evaluating MDM2
      targeted therapies in the context of various accompanying genetic alterations.

PMID- 17201133
TI  - Gefitinib-related gene signature in bladder cancer cells identified by a cDNA
      microarray.
AB  - BACKGROUND: The aim of this study was to identify key genes linked to the
      molecular action of gefitinib, a promising anticancer agent on human bladder
      cancer cell lines. MATERIALS AND METHODS: cDNA microarrays were used to profile
      feature genes in 5637 and T24 cells before and after treatment with gefitinib.
      PCR-based direct sequencing and Western blot analysis were performed to examine
      the mutation status and protein levels of EGFR in the cell lines. RESULTS:
      Gefitinib significantly inhibited the proliferation of 5637 cells, while showing
      little inhibitory effect on T24 cells. Theses effects were independent of the
      mutation status and protein levels of EGFR. cDNA microarray analysis identified
      15 feature genes classified as a cell cycle, apoptotic pathway and transcription.
      Notably, levels of expression of the cell invasion-related genes, YY1 and E
      cadherin, were increased in 5637 cells sensitive to gefitinib. CONCLUSION: Unique
      genes involved in the action of gefitinib were identified. Particularly, the
      upregulation of YY1 and E-cadherin may account for the efficacy of gefitinib in
      bladder cancer.

PMID- 17201134
TI  - Tumorigenic potential and the molecular mechanism of the carcinogenic effect
      exerted by 2-nitroanisole.
AB  - The host-mediated in vitro/in vivo assay system was used to evaluate the
      tumorigenic potential of the aromatic nitro compound 2-nitroanisole (2-NA). After
      intraperitoneal administration of the compound, resident macrophages were
      recovered by peritoneal lavage from treated and untreated mice and cultured in
      soft agar. 2-NA was shown to be carcinogenic, and the tumorigenic potential was
      evaluated. Additionally, by establishment of a transformed peritoneal macrophage
      cell line, the underlying molecular mechanism of 2-NA's carcinogenic effect was
      studied.

PMID- 17201135
TI  - Expression of interleukin-17 in human colorectal cancer.
AB  - The proinflammatory cytokine IL-17 plays a potential role in T-cell mediated
      angiogenesis and promotes tumourigenicity of human cervical cancer. The objective
      of this study was to determine whether IL-17 protein level is altered in
      colorectal tumours (n=74) compared with paired normal mucosa and in plasma from
      patients (n=61) with colorectal cancer (CRC) compared with a healthy group
      (n=78). Analyses by ELISA showed that IL-17 protein was undetectable in 48.6% of
      the patients with cancer, as well as corresponding normal tissue which may in
      part reflect an individual difference. No significant difference was observed
      regarding IL-17 protein levels between cancer and matched normal tissue or in
      plasma between patients and the healthy group. Immunohistochemistry (n=20)
      revealed heterogenous immunoreactivity in 65% of the cases. The results of this
      study suggest that IL-17 plays a minor or partial role in CRC.

PMID- 17201136
TI  - FGFR-2 and -3 play an important role in initial stages of oral oncogenesis.
AB  - BACKGROUND: FGFR-2 and FGFR-3 (fibroblast growth factor receptors) have been
      shown to play an important role in several processes including carcinogenesis.
      This study was designed to determine gradual FGFR-2 and FGFR-3 expression in
      sequential stages of oral carcinogenesis in an experimental animal system of
      Syrian golden hamsters. MATERIALS AND METHODS: Tissue sections ranging from
      normal mucosa to squamous cell carcinoma were studied using monoclonal antibodies
      against FGFR-2 and FGFR-3 proteins. RESULTS: A significant elevation was revealed
      in both FGFR-2 and FGFR-3 expression during the stages of dysplasia and early
      invasion, while in the later stages of oral carcinogenesis the expression of both
      FGFR-2 and FGFR-3 decreased although not significantly. CONCLUSION: Our findings
      indicate that FGFR-2 and FGFR-3 seem to play an important role in the initial
      stages of oral cancer progression.

PMID- 17201137
TI  - Preventive effect of fluvastatin on ulcerative colitis-associated carcinogenesis
      in mice.
AB  - An increased incidence of colorectal carcinoma is known to occur in patients with
      ulcerative colitis (UC), which displays a cycle of recurrence-remission in the
      colorectal mucosa. Fluvastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl
      coenzyme A reductase, is a hypocholesterolemic agent effective in animals and
      humans. Repeated administration of 3% dextran sulfate sodium subsequent to a
      single intraperitoneal injection of azoxymethane induces chronic UC resulting in
      an increased incidence of high-grade dysplasia and submucosal-invasive
      adenocarcinomas in the mouse colorectum. The effects of fluvastatin as an
      antioxidant on colorectal carcinogenesis in mice with UC were investigated.
      Treatment with fluvastatin in mice with UC abolished the anemia caused by
      colorectal carcinogenesis, and markedly lowered plasma lipid levels resulting in
      a reduction of colitis and carcinogenesis, shown by inhibition of the decrease in
      colorectal length, the increased number of foci of gland loss with inflammatory
      cell infiltration indicating the severity of UC and incidence of colorectal
      dysplasia, respectively, with a reduction in anti-8-hydroxy-2'-deoxyguanosine (8
      OHdG) antibody (a biological marker of in vivo oxidative DNA damage)-positive
      cells of the colorectal mucosa and the activity of the DNA-synthesizing enzyme
      thymidine kinase in colorectal tissues.

PMID- 17201138
TI  - Polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) and
      thymidylate synthase enhancer region (TSER) as a risk factor of
      cholangiocarcinoma in a Korean population.
AB  - BACKGROUND: 5,10-Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in
      folate metabolism, plays a major role in the provision of methyl groups for DNA
      methylation; thymidylate synthase (TS) is a rate-limiting enzyme in the synthesis
      of dTMP and DNA repair. The clinical role of genetic polymorphisms of MTHFR and
      that of the TS enhancer region (TSER) were demonstrated in several clinical
      studies with colorectal, esophageal, gastric and breast cancer. However, there
      have never been any studies on the association between cholangiocarcinoma (CCC)
      and genetic polymorphisms of MTHFR and TSER. Therefore, the polymorphism of MTHFR
      and TSER, which share a common substrate, 5,10-methylenetetrahydrofolate, in CCC
      was examined, concurrently. The influence of these polymorphisms on plasma
      homocysteine levels was also investigated. PATIENTS AND METHODS: Blood samples
      were obtained from 47 patients with CCC and 204 healthy control donors. Using
      polymerase chain reaction and restriction fragment length polymorphism (PCR
      RFLP), the C to T transition at position 677 of MTHFR and tandem repeat of 28bp
      in the enhancer region of TS gene were analyzed. Plasma homocysteine levels were
      also determined. RESULTS: According to the logistic regression model, a
      combination of MTHFR 677CC with the TSER 2R(+) genotype had a relative risk of
      5.38 (95% CI, 1.23-23.56) of developing CCC compared to MTHFR 677CC with TSER 2R(
      ) (p = 0.0257). The level of homocysteine was lower in CCC patients than healthy
      controls without statistical significance (8.27 +/- 4.17 vs. 9.40 +/- 2.57, p =
      0.093). CONCLUSION: Our data suggest a role of MTHFR 677CC with the TSER 2R(+)
      genotype in increasing the risk of CCC. This study is the first to suggest an
      association between CCC and the polymorphisms of MTHFR and TSER.

PMID- 17201141
TI  - Cytotoxic efficacy and influence on cellular phospholipid metabolism of 2-hydroxy
      and 2-O-acetyl-octadecylphosphocholines.
AB  - The cytotoxic efficacy and influence on phospholipid composition of the new
      alkylphosphocholines (APC) 2-hydroxy and 2-O-acetyl-octadecylphosphocholines both
      synthesised in R- and S-configuration (R/S-OH and R/S-O-acetyl) were examined in
      vitro using HL-60 and MDA-MB-468 cells. IC50- and LC50-values were measured by
      MTT- and cell count assay. All tested APC showed higher or similar cytotoxic
      efficacy compared to the well known APC hexadecylphosphocholine (HePC). However,
      while S-configured APC (IC50) revealed considerably higher cytotoxic activities,
      only R- (natural)-configured APC caused significant changes in the phospholipid
      composition of tumour cells. Further investigations revealed an increase in R-O
      acyl and loss of PC up to 70% in the membrane of both cell lines. Similar to PC,
      R-O-acyl bears two long non-polar hydrocarbon chains and stabilises cell
      membranes structurally, thus, possibly explaining less cytotoxicity and lack of
      apoptosis induction by R-configured APC. Nevertheless, an enrichment of R-O-acyl
      up to 70% at the expense of PC in cell membrane is tremendous and may inhibit
      tumour development by influencing the intracellular lipid signalling. In
      conclusion, our findings reveal the antitumoral efficacy of all tested new APC
      and offer new perspectives in drug development targeting phospholipid metabolism.

PMID- 17201140
TI  - COX-2 inhibitor celecoxib suppresses tumor growth and lung metastasis of a murine
      mammary cancer.
AB  - BACKGROUND: The antitumor growth and antimetastatic actions of celecoxib [a
      selective cyclooxygenase-2 (COX-2) inhibitor] were investigated in a metastatic
      murine mammary cancer model. MATERIALS AND METHODS: Mice bearing mammary tumors,
      developed after inoculation of syngeneic BALBIc mice with a mammary carcinoma
      cell line carrying a p53 mutation, were treated with celecoxib at 0, 7.5 and 15
      mg/kg five times a week for seven weeks. RESULTS: Tumor volumes were
      significantly reduced in association with an increase in apoptosis and a decrease
      in DNA synthesis in tumor tissues. In vitro studies demonstrated a significant
      increase in the number of cells undergoing apoptosis, with significantly elevated
      activities of caspase-3 and caspase-9, but not caspase-8, and a dose-dependent
      decrease in mitochondrial membrane potential, indicating the mitochondrial
      pathway of apoptosis. In addition, treatment with celecoxib showed cell cycle
      arrest in the G -phase and decreased cell population in the S- and G2/M-phases.
      Furthermore, tumor microvessel formation and mRNA levels for VEGF-A and COX-2
      were markedly decreased. CONCLUSION: Celecoxib may be useful as an adjuvant
      therapy for breast cancer containing p53 mutations due to its ability to both
      induce p53-independent mitochondria-mediated apoptosis and exert anti-angiogenic
      potential.

PMID- 17201142
TI  - Highly-methylated colorectal cancers show poorly-differentiated phenotype.
AB  - The combined methylation status of pl6, pl4, HLTF, SOCS-1, CDH13, RUNX3 and CHFR
      was examined in 58 resected primary colorectal cancers using methylation-specific
      PCR, and the methylation status was correlated with the clinicopathological
      features of the affected patients. A significant difference in histology (p =
      0.0041) was observed when the number of methylated genes of poorly-differentiated
      colorectal cancers was compared to that of other differentiated ones. Poorly
      differentiated colorectal cancers preferentially exhibited gene methylation.

PMID- 17201144
TI  - The emerging world of microRNAs.
AB  - MicroRNAs (miRNAs) are a family of naturally occurring, evolutionary conserved,
      small (approximately 19-23 nucleotides), non-protein-coding RNA molecules that
      generally negatively regulate post-transcriptional gene expression. miRNAs are
      estimated to account for >3% of all human genes and to control expression of
      thousands of target mRNAs, with multiple miRNAs targeting each mRNA. A role for
      miRNAs has been identified in both normal physiological and pathological
      conditions, including metabolism, proliferation, cell death, differentiation and
      development, insulin secretion from pancreatic beta cells, viral infection and
      cancer. Antisense technologies have been successfully used to control miRNA
      expression in vitro and in vivo. Further analysis of this interesting class of
      small RNAs, in normal and pathological conditions, will enable us determine their
      potential to be exploited as therapeutic targets in disease.

PMID- 17201143
TI  - Aberrant methylation of the CHFR gene is frequently detected in non-invasive
      colorectal cancer.
AB  - BACKGROUND: Aberrant methylation of the CHFR gene associated with gene silencing
      has been reported in several primary tumors. In order to define the role of CHFR
      in the tumorigenic pathway of the colorectum, the methylation of CHFR was
      examined in tumors from colorectal cancer patients. MATERIALS AND METHODS: Ninety
      eight colorectal cancer patients were examined using a methylation-specific PCR
      (MSP) for CHFR CpG island in primary tumors. RESULTS: An aberrant methylation of
      the CHFR gene was detected in 25 out of 98 (26%) primary colorectal cancers. No
      methylation was detected in the corresponding normal tissue specimens. This
      finding suggested that an aberrant methylation of the CHFR gene occurs frequently
      in colorectal cancers. After a methylation analysis of all samples, the
      clinicopathological data were correlated with these results. A significant
      difference was found in the tumor (p = 0.035), thus, indicating that in early
      colorectal cancer the CHFR gene was more frequently methylated than in advanced
      cases. CONCLUSION: These findings suggest that CHFR might act as a tumor
      suppressor in at least some colorectal cancers and that CHFR methylation might,
      therefore, be a particular phenomenon of early colorectal cancer.

PMID- 17201139
TI  - HER-2 and NF-kappaB as the targets for therapy-resistant breast cancer.
AB  - HER-2 (also called ErbB2 or Neu) tyrosine kinase, one of the four members of ErbB
      receptor family (ErbB1, i.e., EGFR ErbB2, ErbB3 and ErbB4), plays a critical role
      in the control of diverse cellular functions involved in differentiation,
      proliferation, migration and cell survival via multiple signal transduction
      pathways. Overexpression of HER-2, observed in HER-2-positive breast cancer
      patients, is believed to cause the tumor resistance to an array of anti-cancer
      agents and poor prognosis. Although HER-2 antibodies have shown growth inhibitory
      effects, more efficient molecular targets against HER-2-mediated tumor resistance
      need to be developed. The molecular mechanisms underlying HER-2-mediated tumor
      resistance, especially the connections between HER-2 and therapy-resistant
      signaling networks, need to be further investigated. NF-kappaB, a key stress
      transcription factor that can initiate a pro-survival network, was found to be
      activated in many cancer cells overexpressing HER-2 and to be responsible for the
      radiation resistance in HER-2 transfected breast cancer cells. Recent findings in
      literature and data from this laboratory suggest a possible co-operation between
      HER-2 and NF-KB in signaling tumor resistance to radiotherapy. This review will
      discuss the mechanisms of HER-2 mediated NF-kappaB signaling pathway and
      potential target for therapeutic intervention.

PMID- 17201145
TI  - The protection against trimetrexate cytotoxicity in human bone marrow by sequence
      dependent administration of raloxifene, 5-fluorouracil/trimetrexate.
AB  - BACKGROUND: Currently, one of the most effective strategies for the treatment and
      prevention of breast cancer is the use of drugs that block estrogen action in the
      breast. The success of the first clinically relevant selective estrogen receptor
      modulator (SERM), tamoxifen, provided the foundation for further testing of this
      drug to reduce breast cancer incidence in high-risk women. However, the negative
      effects associated with the long-term use of tanrhoxifen have initiated the
      search for compounds that are more effective but less toxic. The discovery of
      raloxifene (RAL), which functions as a potent antiestrogen in the breast but an
      estrogen receptor (ER) agonist in the bone and cardiovascular system with very
      little uterotropic activity, provided an alternative strategy to the targeted use
      of tamoxifen. The aim of this study was to evaluate RAL in combination with 5
      fluorouracil (5-FU)/trimetrexate (TMX) to determine the most effective regimes
      and cellular mechanism of action to mitigate trimetrexate cytotoxicity in human
      bone marrow cells. MATERIALS AND METHODS: The cell viability was performed using
      the Quick Cell Proliferation Assay by exposing the cells to TMX, 5-FU and RAL
      alone; RAL 24 h prior to 5-FU followed 2 h by TMX, and 5-FU 2 h prior to TMX
      followed 24 h by RAL determined the sequence-dependent interaction between TMX, 5
      FU and RAL on the proliferation. RESULTS: The growth rate in MCF-7 in late RAL
      was 34.75 +/- 4.79% of the control, whereas in bone marrow the same drug
      combination exhibits a significant protection against TMX cytotoxicity with late
      RAL yielding 51.25 +/- 4.43% of the control. The findings were also supported by
      Cell flow cytometry and Western blot analysis. CONCLUSION: Sequence-dependent
      administration of RAL in combination with 5-FU/TMX can act against TMX toxicity
      in human bone marrow, while not affecting the maximum inhibitory effect of TMX in
      breast cancer.

PMID- 17201146
TI  - Analyses of promoter hypermethylation for RUNX3 and other tumor suppressor genes
      in nasopharyngeal carcinoma.
AB  - BACKGROUND: Aberrant methylation of cytosine in promoter CpG islands is a
      recognized contributory process to carcinogenesis. This study explores the
      methylation profile of RUNX3 in combination with p16, RASSF1A, CDH1 and hMLH1 in
      nasopharyngeal carcinoma (NPC) patients. MATERIALS AND METHODS: Genomic DNA was
      extracted from 19 fresh frozen NPC biopsies, which were then subjected to
      bisulfite conversion and methylation-specific PCR for analysis of promoter
      hypermethylation for the five respective genes. Three cell lines, SNU1, RKO and
      LS174T, were used as controls. RESULTS: The incidences of promoter methylation
      were as follows: RUNX3 0/19 (0%), p16 6/19 (32%), RASSF1A 13/19 (68%), CDH1 9/19
      (47%) and hMLH1 4/19 (21%). Ninety-five percent of the tumor specimens displayed
      aberrant methylation in at least one of these genes. No significant correlation
      between methylation status of these genes and clinical parameters was found.
      CONCLUSION: Methylation of multiple genes is involved in critical pathways for
      cancer development in NPC. Promoter hypermethylation for RUNX3 was, however, not
      present.

PMID- 17201147
TI  - Relationship between N-linked oligosaccharide chains of human serum
      immunoglobulin G and serum tumor markers with non-small cell lung cancer
      progression.
AB  - BACKGROUND: It has been demonstrated that increased expression of the sialyl
      Le(x) sugar chains on cancer cells influences cellular adhesion to vascular
      endothelial cells. Therefore, it was thought that alterations in the sugar chain
      structure of E-cadherin, a calcium dependent adhesion molecule, influence the
      metastasis of cancer cells. MATERIALS AND METHODS: In this study, N-linked
      oligosaccharides of human serum immunoglobulin G (IgG) were analyzed in 12
      patients with non-small cell lung cancer (NSCLC) (6 localized cancer: 3
      adenocarcinomas and 3 squamous cell carcinomas; 6 metastatic cancer: 3
      adenocarcinomas and 3 squamous cell carcinomas) and 10 healthy controls using
      fluorophore-associated carbohydrate electrophoresis (FACE). The relationship
      between changes in sugar chain structure and serum concentrations of
      carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) were
      evaluated. CEA levels in the sera were determined using an enzyme immunoassay,
      and CYFRA21-1 levels were determined using an enzyme chemiluminescent
      immunoassay. RESULTS: Fri (monogalactosyl IgG oligosaccharides) and Fr2
      (digalactosyl IgG oligosaccharides) decreased, while Fr4 (agalactosyl IgG
      oligosaccharides) significantly increased (p < 0.01-0.05) with NSCLC progression.
      The Fr4/Fr1+Fr2 ratio increased with NSCLC progression, and the ratios in
      localized and metastatic NSCLC were significantly higher than in healthy controls
      (p < 0.01 and p < 0.01, respectively). There was a strong correlation between
      serum CEA levels and Fr4 (r = 0.91) and a significant correlation between serum
      CEA levels and the Fr4/Fr1+Fr2 ratio (r = 0.83, p < 0.05) in patients with lung
      adenocarcinoma. There was a significant correlation between serum CYFRA21-1
      levels and Fr4 (r = 0.88, p < 0.001) and a positive correlation between serum
      CYFRA21-1 levels and the Fr4/Fr1+Fr2 ratio (r = 0.38) in patients with lung
      squamous cell carcinoma. CONCLUSION: The analysis of serum IgG N-linked
      oligosaccharide chain structures by FACE may be an auxiliary indicator of serum
      tumor markers for monitoring NSCLC progression.

PMID- 17201148
TI  - Homozygous deletions of the INK4a/ARF locus in renal cell cancer.
AB  - BACKGROUND: Genetic alterations of p14ARF contribute to dysfunction of p53
      pathways by disruption of MDM2-mediated inhibition of p53. P14(ARF) was
      investigated by focusing on the homozygous deletion (HD) in the INK4a/ARF locus
      and hypermethylation of the p14(ARF) promoter in renal cell cancer (RCC).
      MATERIALS AND METHODS: Using 6 RCC cell lines, RT-PCR and Western blotting was
      performed for p14(ARF). DNA from 34 RCCs was analyzed for HD in the INK4a/ARF
      locus, promoter hypermethylation and p53 gene mutation. RESULTS: HD was confirmed
      in 4 out of 6 cell lines and in 8 out of 34 (23.5%) RCC specimens, which
      correlated with the presence of metastasis, high tumor grade and had a tendency
      to more advanced stage (I vs. II-IV). No hypermethylation of the p14(ARF)
      promoter or p53 mutation was detected among the RCC specimens. CONCLUSION: These
      results indicate that the deletion in the INK4a/ARF locus might contribute to
      tumor progression in RCC at least partly by functional inactivation of wild-type
      p53.

PMID- 17201149
TI  - Expression of VEGF and its receptors and angiogenesis in bone and soft tissue
      tumors.
AB  - BACKGROUND: Tumor angiogenesis and vascularization are essential requirements for
      the growth and metastasis of tumors. There is evidence that overexpression of the
      vascular endothelial growth factor (VEGF) is correlated with an adverse prognosis
      in some tumors. The expression of VEGF, its receptors and microvessel density
      (MVD) of bone and soft tissue tumors was evaluated. MATERIALS AND METHODS: Tissue
      specimens of 60 patients including 30 malignant and 30 benign tumors confirmed by
      biopsy were examined. Expression of VEGF and its receptors (flt-1 and KDR/flk-1)
      was observed by immunohistochemistry. Tumor angiogenesis was assessed
      morphologically by measuring intratumoral MVD. RESULTS: Semi-quantitative
      evaluation of immunoreactivity showed that VEGF was significantly higher in
      malignant tumors than in benign tumors. A correlation was found between the
      immunoreactivity of VEGF and KDR. Moreover, correlations were found either
      between MVD and VEGF or between MVD and KDR/flk-1. CONCLUSION: Signal
      transduction, in particular by VEGF and KDR, potentially contributes to the
      angiogenesis of bone and soft tissue tumor.

PMID- 17201150
TI  - Gypenosides induced apoptosis in human colon cancer cells through the
      mitochondria-dependent pathways and activation of caspase-3.
AB  - The effects of the gypenosides (Gyp), a component of Gynostemma pentaphyllum
      Makino, on the cell viability, cell cycle and induction of apoptosis were
      investigated in human colon cancer colo 205 cells. Gyp was cytotoxic to colo 205
      cells with an IC50 of 113.5 microg/ml. The decreasing number of viable cells
      appeared to be due to the induction of cell cycle arrest and apoptotic cell
      death, since Gyp induced morphological changes and internucleosomal DNA
      fragmentation and increased the sub-G1 group. The production of reactive oxygen
      species and Ca2+ and the depolarization of mitochondrial membrane potential were
      observed, dose- and time-dependently, after treatment with various concentrations
      of Gyp. Gyp treatment also gradually decreased the expression of the anti
      apoptotic proteins Bcl-2 and Bcl-xl, but increased the expression of the pro
      apoptotic protein Bax. Gyp increased the levels of p53 and promoted the release
      of cytochrome c and the activation of caspase-3 before leading to apoptosis.
      These results provide information towards an understanding of the mechanisms by
      which Gyp induces cell cycle arrest and apoptosis in human colon cancer cells.

PMID- 17201151
TI  - OK432-activated natural killer cells enhanced trastuzumab (Herceptin)-mediated
      antibody-dependent cellular cytotoxicity in patients with advanced cancer.
AB  - BACKGROUND: Adoptive immunotherapy using natural killer (NK) cells from cancer
      patients yielded only modest success. Whether Herceptin and OK432-activated NK
      cells (NK cells obtained by stimulating peripheral blood mononuclear cells with
      OK432 and interleukin-2) improve the outcome of adoptive immunotherapy against
      HER-2/neu positive tumor cells via antibody-dependent cellular cytotoxicity, was
      examined in vitro. MATERIALS AND METHODS: A 51Cr release assay was performed to
      assess cytotoxicity. OK432-activated NK cells and lymphokine-activated killer
      (LAK) cells from healthy donors and cancer patients were used as effectors. Three
      cell lines expressing different amounts of HER-2/neu served as targets. RESULTS:
      In the case of effectors from patients, OK432-activated NK cells showed higher
      cytotoxicity than that of LAK cells, and the cytotoxicity of OK432-activated NK
      cells against the SK-BR-3 cell line (over-expressing HER-2/neu) was increased by
      Herceptin. CONCLUSION: Combination of Herceptin and OK432-activeted NK cells may
      improve the efficacy of the treatment for HER-2/neu-positive malignancy.

PMID- 17201153
TI  - PAI-1 expression levels in esophageal and colorectal cancers are closely
      correlated to those in corresponding normal tissues.
AB  - To investigate the mechanism of PAI-1 overexpression in esophageal and colorectal
      cancers, PAI-1 expression levels in these cancers were compared to those in
      corresponding normal tissues. Quantitative RT-PCR was performed for the PAI-1
      gene in esophageal and colorectal cancer tissues and in the corresponding normal
      tissues and the association between PAI-1 expression levels in these tissues was
      evaluated. There was a significant correlation between esophageal and colorectal
      cancer and the corresponding normal PAI-1 expressions with a Spearman's rank
      correlation coefficient of 0.77 (p < 0.0001) and 0.81 (p < 0.0001), respectively.
      In previous studies, PAI-1 overexpression was found to be significantly
      associated with the malignancy of esophageal and colorectal cancers. Taken
      together, PAI-1 overexpression in esophageal and colorectal cancers might
      originate from higher PAI-1 expression in corresponding normal tissues and result
      in a malignant phenotype of these cancers.

PMID- 17201152
TI  - Cytotoxic activity of selected trifluoromethyl ketones against oral tumor cells.
AB  - Several trifluoromethyl ketones (TF1-4) and related non-fluorinated ketones (TF5
      and 6) were tested for their relative cytotoxicity on four human tumor cell lines
      (oral squamous cell carcinoma HSC-2, HSC-3, HSC-4 and promyelocytic leukemia HL
      60) and three normal human cells [gingival fibroblasts (HGF), pulp cells (HPC)
      and periodontal ligament fibroblasts (HPLF)]. Trifluoromethylated a-diketone
      (TF1, CF3COCOPh) and alpha-hydroxy ketones (TF2, CF3CH(OH)COPh; TF3,
      CF3CH(OH)COCH2Ph) showed higher tumor-specific cytotoxic activity than the
      corresponding non-fluorinated analogs (TF5, CH3COCOPh; TF6, CH3CH(OH)COPh), while
      the anti-tumor potency of trifluoromethyl ketone (TF4, CF3COCH2Ph) was lower.
      Among four tumor cell lines, HL-60 cells were the most sensitive to TF1-4,
      followed by HSC-2 and HSC-3 cells. HSC-4 cells were the most resistant in most
      cases. Agarose gel electrophoresis showed that TF1-3 did not induce
      intemucleosomal DNA fragmentation nor activated caspase-3. The cytotoxic
      activities of TF1-3 were not significantly affected by FeCl3. Electron microscopy
      of TF2- or 3-treated HL-60 cells showed the development of autophagosomes in HL
      60 cells, without the production of an apoptotic body, or affecting the
      mitochondria and cell surface microvilli. The autophagy inhibitor, 3
      methyladenine (3-MA), partially inhibited the TF2- or 3-induced cytotoxicity.
      These data suggest the induction of non-apoptotic cell death by TF2 or 3.

PMID- 17201154
TI  - Reduced heterochromatin protein 1-beta (HP1beta) expression is correlated with
      increased invasive activity in human melanoma cells.
AB  - Heterochromatin protein 1 (HP1) is associated with heterochromatin formation and
      the regulation of gene expression. In this study, we demonstrated that decreased
      HP1beta, but not HPla, mRNA and protein expression, correlates with invasive
      potential in five human melanoma cell lines, and we used immunohistochemistry to
      confirm that HP1beta expression is suppressed during melanoma progression. HPIP
      levels are decreased in (V600E)B-RAF-transformed mouse melanocytes, suggesting
      that HP1beta-mediated suppressive mechanisms correlate with melanoma oncogenesis.
      Expression of microphthalmia associated-transcription factor (MITF), an important
      melanocyte differentiation factor, is reduced in melanoma, which is correlated
      with poor prognosis. In CRL1579, SK-MEL-28 and HMV-II human melanoma cells in
      which HP1beta expression is reduced by RNAi, MITF RNA levels and invasiveness
      activities are differentially altered and are not correlated with each other. Our
      findings indicate that the (V600E)B-RAF mutation induces HPIbeta down-regulation,
      which causes epigenetic gene regulation associated with melanoma progression.

PMID- 17201155
TI  - Lymph node metastases displaying lower Ki-67 immunostaining activity than the
      primary breast cancer.
AB  - The aim of the study was to verify by Ki-67 immunostaining if any difference
      exists in the cell proliferating fraction between primary breast tumors (PTs) and
      matching positive axillary lymph nodes (ALNs). PATIENTS AND METHODS:
      Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in
      160 node-positive breast carcinomas and in their respective lymph node
      metastases. RESULTS: An increase of Ki-67 immunoreactive cells in ALN compared
      with that of PTs was observed in 84% of cases (ALN: mean 17%, PTs: mean 8%; p <
      0.001), whereas 16% of the cases showed Ki-67 value two to six times lower in the
      ALNs than in the corresponding PTs (ALN: mean 3.2%, PTs mean 12.5%; p < 0.005).
      The decrease of Ki-67 positive cells in the ALN was independent from the
      histotype and the histological grade of the tumor. CONCLUSION: A different cell
      proliferation fraction between PTs and matching positive ALNs was demonstrated
      and underlined that the existence of a group of patients with decreased number of
      Ki-67 immunoreactive cells in lymph node metastases compared with that of the
      primary tumors could be taken into account in the choice of therapeutic strategy.

PMID- 17201156
TI  - Curcumin-induced cell cycle arrest and apoptosis in human acute promyelocytic
      leukemia HL-60 cells via MMP changes and caspase-3 activation.
AB  - Curcumin (diferuloylmethane), is a natural product derived from the root of the
      plant Curcuma longa. For centuries, it has been used as a spice and as a herbal
      medicine in Chinese populations. Curcumin has been shown to inhibit cell
      proliferation, cell cycle arrest, cyclooxygenase (COX)-1 and -2 expression and
      apoptosis in several human cancer cell lines. The aim of this investigation was
      to clarify the mechanisms by which curcumin induced cytotoxicity and apoptosis in
      human leukemia HL-60 cells. The effects of curcumin on the levels of reactive
      oxygen species (ROS), Ca+2 production, cyclin E, cdc25c, wee1, Bcl-2, Bax, the
      changes of mitochondrial membrane potential (MMP), cytochrome c release and the
      activation of caspase-3 were also investigated in the HL-60 cells. Results of
      flow cytometry and DAPI staining assays indicated that curcumin induced
      cytotoxicity and apoptosis in the examined cells. The results from flow cytometry
      assay indicated that curcumin induced ROS and Ca+2 productions, decreased the
      levels of MMP and increased the activity of caspase-3, leading to cell apoptosis.
      Western blot assay also revealed that curcumin increased the levels of Bax and
      the release of cytochrome c, and decreased the levels of Bcl-2 in the examined
      cells. The inhibition of caspase-3 activation by z-VAD-fmk (broad-spectrum
      caspase inhibitor) completely blocked curcumin-induced apoptosis in HL-60 cells.

PMID- 17201157
TI  - False-positives in fine-needle aspiration cytology of breast disease can be
      reduced with p63 immunostaining--a preliminary report.
AB  - Myoepithelial cells of the mammary gland are considered to be a key to
      distinguishing benign from malignant disease in fine-needle aspiration (FNA)
      cytology. However, identification of these cells with Papanicolaou staining is
      not easy. The identification of myoepithelial cells was investigated using p63
      antibodies to carry out immunostaining of FNA specimens that had been used at the
      time of Papanicolaou staining for 37 patients who yielded false-positives in FNA.
      Positively-stained cells were observed in overlying cell clusters or the
      background in 67.6% of the patients. There is a possibility that over-diagnosis
      could have been avoided by performing p63 staining for these patients. The
      controls consisted of stamp samples of fresh specimens obtained from 23 patients
      at the time of surgery for invasive carcinoma and the results of p63
      immunostaining did not reveal any positive staining of tumor cells. Accordingly,
      these results indicate that there is a strong likelihood that there is no
      invasive carcinoma when many p63-positive cells are observed in the tumor cell
      population or the background and that p63 immunostaining has the potential to aid
      in reducing false-positives at the time of FNA diagnosis of breast disease.

PMID- 17201159
TI  - Decreased expression of tumor protein p53-induced nuclear protein 1 (TP53INP1) in
      breast carcinoma.
AB  - BACKGROUND: Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a stress
      induced protein and plays a role in cell cycle arrest and p53-mediated apoptosis.
      In this study, TP53INP1 expression in human breast carcinoma was investigated.
      MATERIALS AND METHODS: TP53INP1 and aberrant p53 expression were investigated
      immunohistochemically in 81 cases of breast carcinoma. RESULTS: Diffuse and
      intense TP53INP1 expression was observed in the normal mammary gland. Decreased
      TP53INP1 expression was found in 45 cases (55.6%) of breast carcinoma. The
      TP53INP1 expression level was inversely linked to tumor size, positive lymph node
      metastasis, high histological grade and aberrant p53 expression. CONCLUSION:
      Decreased expression of TP53INP1 is involved in breast carcinoma progression.

PMID- 17201158
TI  - Curcumin-induced apoptosis of human colon cancer colo 205 cells through the
      production of ROS, Ca2+ and the activation of caspase-3.
AB  - Curcumin (diferuloylmethane), the yellow pigment in turmeric (Curcuma longa), is
      known to inhibit proliferation of cancer cells by arresting them at various
      phases of the cell cycle and to induce apoptosis in tumor cells. Curcumin-induced
      apoptosis mainly involves the activation of caspase-3 and mitochondria-mediated
      pathway in various cancer cells of different tissue origin. In the present study,
      the induction of apoptosis and cytotoxicity by curcumin in colon cancer colo 205
      cells was investigated by using flow cytometry. The results demonstrated that
      curcumin induced cytotoxicity and apoptosis dose- and time-depedently. Curcumin
      induced the production of reactive oxygen species (ROS) and Ca+2, decreased the
      levels of mitochondria membrane potential and induced caspase-3 activity.
      Curcumin also promoted the expression of Bax, cytochrome C, p53 and p21 but
      inhibited the expression of Bcl-2. These observations suggest that curcumin may
      have a possible therapeutic potential in colon cancer patients.

PMID- 17201160
TI  - Epidermal growth factor receptor changes during breast cancer metastasis.
AB  - BACKGROUND: Since the anti-HER2 monoclonal antibody trastuzumab made its
      triumphant advance into breast cancer therapy, new selective agents, including
      pan-HER inhibitors are entering clinical practice. MATERIALS AND METHODS: This
      study investigates the expression of the four HER-family members, HER1-4, in 48
      primary breast carcinomas (PBC) and corresponding distant metastases (CDM) by
      immunohistochemistry and fluorescence in situ hybridisation. RESULTS: Concordance
      rate between PBC and CDM was 79% for HERI and HER2, 67% for HER3 and 56% or HER4.
      Expression of HER1-3 was associated with poor prognosis compared to HER-negative
      disease (p = 0.036). HER4 overexpression was associated with a better outcome (p
      = 0.003). CONCLUSION: Though most tumours demonstrate a stable HER expression
      pattern, both loss and acquisition of HER receptor overexpression can occur
      during metastasis. HER4 overexpression predicts prolonged survival compared to
      receptor negative disease, while the opposite is true for HER1-3. Consequences
      for modem antibody therapy are discussed.

PMID- 17201161
TI  - Effect of resveratrol and mixtures of resveratrol and mitomycin C on cancer cells
      under irradiation.
AB  - The radiation-biological effects of resveratrol (Res) alone or with mitomycin C
      (MMC) were investigated under various conditions in human breast cancer cells
      (MCF-7). The data of the survival curves obtained in aerated media (acting
      species: 42% OH, 54% 02*-) showed that Res possesses antitumor activity and also
      acts as an efficient radical scavenger. This property was extremely enhanced in
      the presence of MMC. In media saturated with N2O (90% OH, 10% H) Res at low
      concentrations acted as a radiation-protecting agent, but at higher
      concentrations its cytostatic effect predominated. At the same time, the MMC
      activity was reduced. In anaerobic media, Res demonstrated its radiation
      protecting ability, but in mixtures the MMC-ability was reduced in comparison to
      that of pure MMC due to competition reactions between Res and MMC for the
      available free radicals. Finally, in a cell suspension containing formate as a
      specific scavenger for OH and H radicals (pH = 7.4), Res successfully competed
      for these species and showed antitumor activity. Considering the reaction rate
      constants of the involved substrates and the implemented concentrations in each
      medium, the kinetic probability of each survival curve was calculated. Based on
      these data it was evident that the bifunctional property of Res (acting as
      radiation protector and also having antitumor activity) was based on an electron
      ejection process from its excited single state and on its reactivity with the
      primary radicals (OH, H, e(aq)-).

PMID- 17201162
TI  - Toll-like receptor interference in myeloid dendritic cells through head and neck
      cancer.
AB  - BACKGROUND: In head and neck squamous cell carcinoma (HNSCC) the secretion of
      various immunosuppressive mediators contributes to large-scale effects on the
      immune functions. The influence of HNSCC on the Toll-like receptor (TLR)
      expression profiles of human myeloid dendritic cells (MDCs), which have been
      identified in human solid tumor tissue of the head and neck, was analysed.
      MATERIALS AND METHODS: MDCs were isolated from peripheral blood by 'magnetic bead
      separation' and subsequently incubated with supernatants of HNSCC permanent cell
      lines. TLR expression profiles were investigated using Af cytometry and SDS-PAGE.
      RESULTS: Human MDC from peripheral blood were found to express all human TLRs
      except TLR4 and TLR9. Incubation of MDC with supernatants of HNSCC resulted in an
      increased expression of TLR7. CONCLUSION: The data suggest an interference of
      TLR7 expression through HNSCC and provide novel evidence of TLR alterations as a
      potential tumor promoting event in head and neck cancer.

PMID- 17201163
TI  - Cyclin A and E2F1 overexpression correlate with reduced disease-free survival in
      node-negative breast cancer patients.
AB  - BACKGROUND: Available prognostic factors do not accurately identify node-negative
      breast cancer patients at high risk of disease recurrence and progression.
      PATIENTS AND METHODS: Cyclin A and E2F1 expression levels were evaluated in 75
      consecutive node-negative breast cancer patients with a median follow-up of 10
      years. Both parameters were tested for correlation with all the available
      clinicopathological parameters and with the clinical evolution of the disease.
      RESULTS: Cyclin A was overexprNed in 45.3% of patients and significantly related
      to large tumor size, high Ki67 and high E2F1 expression levels. No relationship
      was observed between cyclin A and tumor estrogen receptor (ER) status, grading or
      patient age. Seventeen patients relapsed within 5 years from diagnosis. Twelve
      (71%) of them showed cyclin A overexpression in comparison with 22 (38%) out of
      the 58 who did not relapse (p = 0.02). Disease-free survival (DFS) was
      significantly shorter in patients with cyclin A-overexpressing tumors compared to
      non-overexpressing ones (p = 0.01). DFS was also significantly longer in low vs.
      high Ki67 expression (p = 0.003) and in low vs. high E2F1 expression (p = 0.02).
      On multivariate analysis, the simultaneous high expression of all three
      parameters (cyclin A, Ki67 and E2Fl) was a strong independent prognostic factor
      for shorter DFS (HR 13.4). CONCLUSION: These findings suggest that assessment of
      cyclin A and/or E2F1 expression levels, associated with Ki67, might be useful for
      a better prognostic evaluation of node-negative breast cancer patients and
      support the need for further studies to evaluate their suitability for use in the
      routine clinical management of these patients.

PMID- 17201164
TI  - Inhibition of pancreatic and lung adenocarcinoma cell survival by curcumin is
      associated with increased apoptosis, down-regulation of COX-2 and EGFR and
      inhibition of Erk1/2 activity.
AB  - BACKGROUND: Several studies suggested that curcumin inhibits growth of malignant
      cells via inhibition of cyclooxygenase-2 (COX-2) activity. Other studies
      indicated that epidermal growth factor receptor (EGFR) is also inhibited by
      curcumin in vitro and in vivo. Moreover, recent investigations revealed an
      intracellular cross-talk between EGFR signaling and the COX-2 pathway. Our aim
      was to evaluate whether the curcumin inhibitory effect on the survival of cancer
      cells is associated with simultaneous down-regulation of COX-2 and EGFR and
      inhibition of Erk1/2 (extra-cellular signal regulated kinase) signaling pathway.
      MATERIALS AND METHODS: Lung and pancreas adenocarcinoma cell lines co-expressing
      COX-2 and EGFR (PC-14 and p34, respectively) and those expressing EGFR but
      deficient in COX-2 (H1299 and Panc-1, respectively) were exposed for 72 h to
      curcumin (0-50 microM). Cell viability was assessed by the XTT assay. Apoptosis
      was determined by FACS analysis. COX-2, EGFR, ErbB-2 and p-Erk1/2 expressions
      were measured by Western blot analysis. RESULTS: Curcumin's inhibitory effect on
      survival and apoptosis of lung and pancreatic adenocarcinoma cell lines was
      significantly higher in the COX-2-expressing cells than in the COX-2-deficient
      cells. In the p34 and PC-14 cells, curcumin decreased COX-2, EGFR and p-Erk1/2
      expressions in a dose-dependent manner. However, in the Panc-1 and H1299 cell
      lines, which did not express COX-2, curcumin did not affect EGFR levels.
      CONCLUSION: Curcumin co-inhibited COX-2 and EGFR expression and decreased Erk1/2
      activity. This inhibition was associated with decreased survival and enhanced
      induction of apoptosis in lung and pancreatic adenocarcinoma cells.

PMID- 17201165
TI  - CHS 828 kill tumour cells by inhibiting the nuclear factor-kappaB translocation
      but unlikely through down-regulation of proteasome.
AB  - CHS 828 (N-(6-chlorophenoxyhexyl)-N'cyano-N"-4-pyridylguanidine) has shown
      promising activity in many preclinical systems and in phase I/II clinical trials.
      The nuclear transcription factor kappa B (NF-kappaB) has been identified as a
      target for CHS 828. The aim of this study was to confirm the inhibitory effect of
      CHS 828 on NF-kappaB translocation and to explore its possible effect on the
      proteasome using 7 cell lines. Translocation of NF-kappaB from the cytoplasm to
      the nucleus was analysed using a quantitative cytometric system, ArrayScan. The
      activity of the proteasome was assayed by monitoring the hydrolysis of a
      fluorogenic substrate. In parallel, the in vitro cytotoxic effect of CHS 828 was
      analyzed using a 72-h microtiter plate-based cytotoxicity assay (FMCA). CHS 828
      inhibited NF-kappaB translocation in the cell lines where it was able to inhibit
      the tumour cell growth. However, the results did not prove any effect of CHS 828
      on proteasome activity when compared to a proteasome inhibitor activity.

PMID- 17201166
TI  - Growth-suppressive function of phosphatidylethanolamine-binding protein in
      anaplastic thyroid cancer.
AB  - BACKGROUND: A cDNA microarray analysis of anaplastic thyroid cancer cell lines
      (ACL) was recently performed and the down-regulation of phosphatidylethanolamine
      binding protein (PBP) [RAF kinase inhibitor protein (RKIP)] in ACL compared to
      normal thyroid tissues was identified. MATERIALS AND METHODS: The expression
      levels of PBP in primary anaplastic and papillary thyroid cancer, thyroid cancer
      cell lines (anaplastic, papillary and follicular) and several normal human organs
      were examined. To examine the function of PBP, cell-growth assays were performed.
      RESULTS: PBP expression was reduced in anaplastic thyroid cancers, compared to
      either normal thyroid tissues or differentiated thyroid cancers. PBP was
      expressed ubiquitously in normal human tissues. Exogenous PBP expression
      suppressed ACL growth, and suggested a tumor suppressive function of PBP in ACL.
      CONCLUSION: This is the first report demonstrating that PBP may be a tumor
      suppressor whose loss is associated with development of anaplastic thyroid cancer
      from differentiated thyroid cancer.

PMID- 17201167
TI  - Histamine inhibits cell proliferation and modulates the expression of Bcl-2
      family proteins via the H2 receptor in human pancreatic cancer cells.
AB  - In this study, the mechanisms involved in the inhibitory effect of histamine (HA)
      on PANC-1 cell proliferation were investigated. The action of HA on cell growth
      was evaluated by determining the cell doubling time from experimental growth
      curves and analysing the cell cycle using a flow cytometer. The expression of
      proteins related to cell death and proliferation (PCNA, p53, c-Fos and Bcl-2
      family proteins) was studied using Western blot, immunocytochemistry and flow
      cytometric analysis. The results indicated that HA produced an accumulation of
      PANC-1 cells in GO/Gl-phase and increased the doubling time via H2HA (H2R)
      stimulation. Expression of p53, c-Fos and Bcl-2 were not modulated by HA.
      However, HA decreased PCNA and Bax expression, while it increased the Bcl-x
      level. In summary, the antiproliferative effect exerted by HA was associated with
      a G0/G1-phase arrest and a modulation of the Bcl-2 family proteins.

PMID- 17201168
TI  - Intratumoral application of standardized mistletoe extracts down regulates tumor
      weight via decreased cell proliferation, increased apoptosis and necrosis in a
      murine model.
AB  - The cytotoxic in vitro activity of standardized mistletoe extracts (ME) was
      examined by established assays towards the human ductal breast carcinoma cell
      line BT474. A dose-dependent (optimum 25 mg/mL medium) and significantly (p <
      0.05) enhanced cytotoxic activity towards the BT474 cells was demonstrated. In
      vivo experiments on the antitumor activity of ME-A and ME-M were performed in a
      BALB/c-mouse / BT474 ductal breast carcinoma model. ME-A and ME-M were
      intratumorally administered according to an application schedule which was found
      to be optimal concerning dosage and time of administration. Standardized
      intratumoral application of ME-A and ME-M induced a significantly (p < 0.05)
      decreased tumor weight in experimental mice. Histological investigations were
      performed comprising analysis of mitosis and proliferation rates (Ki67
      expression), as well as necrosis and apoptosis induction (ssDNA detection). As
      compared to tumors of control mice with intratumoral phosphate-buffered saline
      (PBS) injections, tumors of the ME-A and ME-M treated groups showed a decreased
      cell proliferation rate, as well as an increased cell necrosis and apoptosis
      rate. Standardized mistletoe extracts, interfering with defined tumor cell
      functions, e.g., proliferation, necrosis and apoptosis, may have an impact on
      local cancer treatment.

PMID- 17201170
TI  - Activity of bortezomib in glioblastoma.
AB  - BACKGROUND: Chemotherapy is the commonly accepted standard therapy for most types
      of brain tumor, especially in medulloblastoma, primitive neuroectodermal tumor
      and astrocytoma. However, no efficient therapy has been established to date for
      glioblastoma multiforme. The aim of the present study was to analyze the activity
      of bortezomib in glioblastoma cell lines in comparison with that in a pediatric
      acute lymphoblastic leukemia cell line. MATERIALS AND METHODS: Glioblastoma
      multiforme T98G, glioblastoma-astrocytoma U373M and T-lineage acute lymphoblastic
      leukemia CCRF-CEM cell lines were used. Proteasome inhibitor, bortezomib and 14
      other anticancer drugs were tested using the MTT assay. RESULTS: Compared to the
      acute lymphoblastic cell line, both glioblastoma cell lines showed relatively
      good sensitivity to bortezomib, as well as to cisplatin, carboplatin, etoposide
      and actinomycin-D. The lines showed intermediate sensitivity to thiotepa and
      daunorubicin, but were highly resistant to first-line drugs used in the therapy
      of acute lymphoblastic leukemia, such as prednisolone, L-asparaginase,
      vincristine, doxorubicin and cytarabine. Bortezomib, which is not a substrate for
      PGP and MRP1, did not show cross resistance to drugs transported by these
      proteins. CONCLUSION: Our results support the necessity for further research on
      the role of bortezomib in the therapy of glioblastoma.

PMID- 17201169
TI  - Anticancer potential of silymarin: from bench to bed side.
AB  - Silymarin consists of a family of flavonoids (silybin, isosilybin, silychristin,
      silydianin and taxifoline) commonly found in the dried fruit of the milk thistle
      plant Silybum marianum. Although silymarin's role as an antioxidant and
      hepatoprotective agent is well known, its role as an anticancer agent has begun
      to emerge. Extensive research within the last decade has shown that silymarin can
      suppress the proliferation of a variety of tumor cells (e.g., prostate, breast,
      ovary, colon, lung, bladder); this is accomplished through cell cycle arrest at
      the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21
      and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl
      xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of
      inflammatory transcription factors (e.g., NF-kappaB). Silymarin can also down
      regulate gene products involved in the proliferation of tumor cells (cyclin D1,
      EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and
      metastasis (adhesion molecules). The antiinflammatory effects of silymarin are
      mediated through suppression of NF-kappaB-regulated gene products, including COX
      2, LOX, inducible iNOS, TNF and IL-1. Numerous studies have indicated that
      silymarin is a chemopreventive agent in vivo against a variety of
      carcinogens/tumor promoters, including UV light, 7,12-dimethylbenz(a)anthracene
      (DMBA), phorbol 12-myristate 13-acetate (PMA) and others. Silymarin has also been
      shown to sensitize tumors to chemotherapeutic agents through down-regulation of
      the MDR protein and other mechanisms. It binds to both estrogen and androgen
      receptors, and down-regulates PSA. In addition to its chemopreventive effects,
      silymarin exhibits antitumor activity against human tumors (e.g., prostate and
      ovary) in rodents. Various clinical trials have indicated that silymarin is
      bioavailable and pharmacologically safe. Studies are now in progress to
      demonstrate the clinical efficacy of silymarin against various cancers.

PMID- 17201171
TI  - HIF-1alpha mRNA is not associated with histopathological regression following
      neoadjuvant chemoradiation in esophageal cancer.
AB  - BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) expression was reported
      to be associated with tumor growth, progression and resistance to radio
      /chemotherapy. Whether HIF-1alpha mRNA or protein expression is associated with
      histomorphological response or prognosis following neoadjuvant chemoradiation and
      surgery in resectable, locally-advanced esophageal cancer was analyzed. PATIENTS
      AND METHODS: Fifty-three patients received neoadjuvant chemoradiation (cisplatin,
      5-fluorouracil, 36 Gy) followed by transthoracic en bloc esophagectomy. HIF
      1alpha mRNA and protein expressions were analyzed by quantitative RT-PCR and
      immunostaining. RESULTS: In squamous cell carcinoma, HIF-1alpha mRNA expression
      was significantly higher than in paired normal epithelium (p < 0.001). Normal
      squamous epithelium showed significant elevated expression in adenocarcinomas,
      suggesting a field effect (p < 0.04). HIF-1alpha protein expression showed a
      significant regulation following chemoradiation. Neither HIF-1alpha mRNA nor
      protein expression was associated with histomorphological regression or
      prognosis. CONCLUSION: HIF-1alpha mRNA expression is differentially upregulated
      in esophageal squamous cell carcinoma compared to adenocarcinomas, but does not
      predict tumor regression or prognosis.

PMID- 17201172
TI  - Retinoblastoma suppressor associated protein 46 (RbAp46) attenuates the beta
      catenin/TCF signaling through up-regulation of GSK-3beta expression.
AB  - BACKGROUND: BETA-Catenin plays a critical role in embryonic development and
      tumorigenesis through its function in cell-cell adhesion and in the Wnt-dependent
      signaling pathway. Thus, the expression of this important protein is strictly and
      dynamically regulated. MATERIALS AND METHODS: A stable cell line from mammary
      epithelial cells MCF10AT3B that ectropically expresses the retinoblastoma
      suppressor (Rb) associated protein 46 (RbAp46) was established, and used Western
      blot, luciferase and cell growth assays to study the effects of constitutive
      RbAp46 expression. RESULTS: MCF10AT3B cells expressing recombinant RbAp46
      exhibited a decreased rate of cell growth. In RbAp46-expressing cells,
      betacatenin protein was highly phosphorylated and the steady state levels of beta
      catenin protein were significantly decreased. Accordingly, the beta-catenin/TCF
      nuclear signaling was dramatically reduced in RbAp46 expressing cells. In
      addition, expression levels of glycogen synthase kinase-3beta (GSK-3beta) were
      increased in RbAp46 expressing cells. CONCLUSION: RbAp46 plays an important role
      in regulation of beta-catenin expression and the beta-catenin/TCF signaling
      pathway presumably through regulation of GSK-3beta expression.

PMID- 17201173
TI  - The characterization of gefitinib sensitivity and adverse events in patients with
      non-small cell lung cancer.
AB  - BACKGROUND: Factors predicting gefitinib sensitivity and adverse events in non
      small cell lung cancer (NSCLC) remain controversial. PATIENTS AND METHODS:
      Correlations among clinicopathological characteristics, gefitinib sensitivity and
      adverse events were studied in 154 patients with NSCLC, whereas epidermal growth
      factor receptor (EGFR) mutations were analyzed in 44 patients. RESULTS: Female,
      non-smoker, adenocarcinoma of stage I-II, and gefitinib effectiveness correlated
      with longer time to progression (TTP) and overall survival (OS), while the rate
      of interstitial lung disease in patients undergoing thoracic radiotherapy and
      stomatitis in females or those who never smoked were significantly higher. EGFR
      mutations were identified in 18 cases, and among 34 gefitinib-treated patients,
      16 patients harboring mutations tended to do better, both in terms of TTP and OS.
      The results of the mutation analysis from surgical and non-surgical specimens
      were identical. CONCLUSION: Certain clinicopathological characteristics and EGFR
      mutations can be either predictive of gefitinib sensitivity or adverse events.

PMID- 17201174
TI  - Xanthorrhizol exhibits antiproliferative activity on MCF-7 breast cancer cells
      via apoptosis induction.
AB  - Xanthorrhizol is a natural sesquiterpenoid compound isolated from the rhizome of
      Curcuma xanthorrhiza Roxb (Zingiberaceae). Xanthorrhizol was tested for a variety
      of important pharmacological activities including antioxidant and anti
      inflammatory activities. An antiproliferation assay using the MTT method
      indicated that xanthorrhizol inhibited the proliferation of the human breast
      cancer cell line, MCF-7, with an EC50 value of 1.71 microg/ml. Three parameters
      including annexin-V binding assay, Hoechst 33258 staining and accumulation of sub
      G1 population in DNA histogram confirmed the apoptosis induction in response to
      xanthorrhizol treatment. Western-blotting revealed down-regulation of the anti
      apoptotic bcl-2 protein expression. However, xanthorrhizol did not affect the
      expression of the pro-apoptotic protein, bax, at a concentration of 1 microg/ml,
      2.5 microg/ml and 5 microg/ml. The level of p53 was greatly increased, whilst
      PARP-1 was cleaved to 85 kDa subunits, following the treatment with xanthorrhizol
      at a dose-dependent manner. These results, thereby, suggest that xanthorrhizol
      has antiproliferative effects on MCF-7 cells by inducing apoptosis through the
      modulation of bcl-2, p53 and PARP-1 protein levels.

PMID- 17201175
TI  - Expression of erythropoietin receptor in human Merkel cell carcinoma of the
      eyelid.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) of the eyelid is a rare malignant solid
      tumor of the elderly, which demonstrates a large, firm, reddish nodule mimicking
      an angiomatous lesion. The expression of erythropoietin (Epo) and Epo receptor
      (EpoR), as well as vascular endothelial growth factor (VEGF), VEGF receptor
      (VEGFR) and basic fibroblast growth factor (bFGF) were examined in human MCC
      tissues. MATERIALS AND METHODS: Three patients diagnosed with MCC of the eyelid
      underwent surgical excision. Isolated tissues were fixed by 4% paraformaldehyde
      and then were examined using immunohistochemistry. RESULTS: The carcinoma cells
      consisted of irregular tumor nests with linear stroma and showed hypercellularity
      indicated by small round nuclei with several mitoses. While immunoreactivity of
      Epo was undetectable, an increased expression of EpoR was noted in the carcinoma
      cells. Cytoplasmic immunoreactivity for EpoR was detected in a variety of
      carcinoma cells, including mitotic cells. VEGF, VEGFR, and bFGF, other angiogenic
      factors were not expressed in the MCC tissues. CONCLUSION: EpoR was highly
      expressed in MCC of the eyelid, suggesting that the Epo-EpoR pathway plays an
      important role in the formation of MCC.

PMID- 17201176
TI  - The prion-like protein Doppel (Dpl) interacts with the human receptor for
      activated C-kinase 1 (RACK1) protein.
AB  - BACKGROUND: Doppel (Dpl) is a homologue of the prion protein (PrPC). In contrast
      to PrP(C), Dpl is dispensable for prion disease, but appears to have an essential
      function in male spermatogenesis. Recently, Dpl has been found to be aberrantly
      expressed in astrocytic and leukaemic tumor specimens, showing a peculiar
      cytosolic cellular localization. The aim of this study was to clarify some of the
      putative Dpl interacting proteins. MATERIALS AND METHODS: A yeast two hybrid
      system was employed and the results were verified by co-immunoprecipitation using
      transfected cells. RESULTS: Several potential Dpl-binding candidates were
      identified and, among them, the receptor for activated C-kinase (RACK1) protein
      was further investigated. RACK1 deletion mutants showed that some of its WD
      containing domains were directly involved in the binding with Dpl. Our data
      showed that Dpl interacts with RACK1 by means of its structured globular carboxyl
      terminal region. CONCLUSION: This new Dpl interacting partner might suggest
      functional hypotheses about the role of this protein in an astrocytoma context
      where Dpl was found ectopically expressed.

PMID- 17201177
TI  - Fractionated ionizing radiation exposure induces apoptosis through caspase-3
      activation and reactive oxygen species generation.
AB  - BACKGROUND: Radiation therapy (RT) is a well established therapeutic modality for
      the treatment of solid tumors. In particular, post-operative RT is considered the
      standard treatment adjuvant to surgery since its ability to prolong median
      survival of patients with malignant astrocytoma has been shown; nevertheless the
      ionizing radiation (IR) treatment fails in a considerable number of astrocytoma
      patients. MATERIALS AND METHODS: Using an ADF human astrocytoma cell line the
      molecular mechanisms involved in the DNA damage induced by fractionated
      irradiation (FIR) and single IR treatment have been investigated. RESULTS: FIR
      and single IR treatment inhibited the growth of the ADF human astrocytoma cell
      line. FACS analysis revealed that FIR treatment, but not single IR treatment,
      induced growth inhibition associated with the induction of apoptosis. Apoptosis
      was related to caspase-3 activation and reactive oxygen species (ROS) generation.
      ROS formation depends on the up-regulation of the cytochrome P450 enzyme gene. On
      the contrary, 12.5 Gy induced necrotic cell death up-regulating the HSPD1, HSPCB,
      HSPCA and HSPB1 genes. CONCLUSION: FIR treatment induced cell death through
      caspase-3 and ROS-mediated apoptosis.

PMID- 17201178
TI  - Development of rational in vitro models for drug resistance in breast cancer and
      modulation of MDR by selected compounds.
AB  - BACKGROUND: [corrected] The effectiveness of chemotherapy is limited by the
      emergence of multidrug resistance (MDR). MDR is caused by the activity of various
      ATP binding cassette (ABC) transporters that pump anticancer drugs out of the
      cells in an ATP-dependent manner. Additionally some other cellular mechanisms of
      MDR have been reported. The purpose of this study was to investigate mechanisms
      of MDR in drug resistant MCF-7 cell lines and to modulate P-glycoprotein (P-gp)
      and MRP1-based MDR. MATERIALS AND METHODS: Paclitaxel (MCF-7/Pac), docetaxel (MCF
      7/Doc), doxorubicin (MCF-7/Dox) and vincristine (MCF-7/Vinc) resistant sublines
      were developed from the parent MCF-7 cell line (MCF-7/S) by stepwise selection in
      dose increments over two years. Flow cytometry, MTT cytotoxicity assay, RT-PCR,
      caspase-3 activity assay and checkerboard combination assay were performed to
      investigate the degree of resistance developed in sublines and to reverse drug
      resistance phenotype. RESULTS: The flow cytometry histograms of drug accumulation
      assays demonstrated that the drug-resistant cell lines are P-gp and MRPI
      positive. RT-PCR results showed that the resistant sublines express both MDR1 and
      MRP1 genes. Resistance indices of each subline to each anticancer drug were
      determined using the MTT cytotoxicity assay and it was found that all the
      sublines were resistant to their respective agents. Caspase-3 activities of the
      cell lines were also determined. Caspase-3 activity is an important indicator of
      apoptosis in the cell. The reversal of MDR was attempted by two cinnamylidene
      ketone and two organosilicon compounds. The results indicated that these
      compounds modulated P-gp effectively, but they were not very effective at
      reversing MRP1 activity in the MCF-7 sublines. Four selective anticancer drugs
      (paclitaxel, docetaxel, doxorubicin and vincristine) and four synthetic MDR
      modulators [2-(2-methoxycinnamylidene) indan-1-one (cinnamylidene-1), 2-(2-
      methoxycinnamylidene)-3, 4-dihydro-2H-naphthelen-1-one) (cinnamylidene-2), ALIS
      409 and ALIS 421] were applied to the sublines in combination. The fractional
      inhibitory indices illustrated that combined applications of cinnamylidene
      ketones and organosilicon compounds with paclitaxel, docetaxel or vincristine
      exerted significant antiproliferative effects on the resistant sublines.
      CONCLUSION: This report demonstrates the development of rational models for drug
      resistance MCF-7 cell lines and reversal of acquired drug resistance.

PMID- 17201179
TI  - In vitro biocompatibility between mitomycin-C (MMC) and bacillus Calmette-Guerin
      (BCG).
AB  - BACKGROUND: Mitomycin-C (MMC) and bacillus Calmette-Guerin (BCG) intravesical
      instillations are widely and effectively used as adjuvant treatment for
      superficial bladder cancer. In an attempt to improve the efficacy of intravesical
      therapy, MMC and BCG have also been used in a sequential or an alternating mode.
      The aim of this study was to assess the in vitro biocompatibility between these
      agents. MATERIALS AND METHODS: The effect of MMC on BCG clumping tendency was
      assessed by estimating the number of colony forming units (CFU) of BCG in
      suspension, during incubation at 37 degrees C for 3 h, with repeated recordings
      of the suspension optical density (OD). Preparations containing either BCG plus
      MMC or BCG plus an equivalent amount of sterile water were cultivated using the
      non-radiometric system BACTEC MGIT 960. The final concentrations of the agents,
      following transfer of the preparations into the tubes of the system, were 1.25
      mg/ml for BCG and 1 mg/ml for MMC. During the cultivation process, the tubes of
      the system were automatically checked every 60 min for fluorescence emission,
      which is an indication of mycobacteria growth. A comparative cultivation of the
      same preparations on Lowenstein-Jensen solid medium was also performed. RESULTS:
      The OD of the BCG preparation remained almost unaffected for 3 h and was
      minimally altered by inclusion of MMC. After 34-38 h of cultivation in the BACTEC
      MGIT 960 system, all 7 cultures of the BCG+sterile water preparations became
      positive. In contrast, no BCG+MMC specimen became positive after an incubation
      period of 42 days. Following re-cultivation of the 7 negative BCG+MMC specimens,
      6 remained negative, whereas 1 specimen became positive after an incubation
      period of 22 days. On Lowenstein-Jensen medium, growth of mycobacteria was noted
      only in the BCG+sterile water specimens and not in the BCG+MMC specimens.
      CONCLUSION: The results of this study indicate that, although MMC has no apparent
      effect on BCG tendency to form clumps in suspension, it may inhibit its growth in
      vitro. However, this does not necessarily compromise BCG anti-tumour activity. As
      the in vivo interaction of the drugs may be different, the efficacy of the
      combined BCG+MMC treatment should be defined in clinical trials.

PMID- 17201180
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on leukocyte function-associated
      antigen-1 mediated splenocyte adhesion.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental
      contaminant that induces various types of immunotoxicity. One effect of exposure
      to this contaminant is alteration in cell adhesiveness. Leukocyte function
      associated antigen-1 (LFA-1) plays an important role not only in T-cell
      recruitment into sites of inflammation and lymphoid tissues, but also in T-cell
      activation and in the development of specific immune responses. We, therefore,
      examined whether the alteration in cell adhesiveness is associated with the
      modulation of LFA-1 expression and its second messengers following exposure to
      TCDD. In vitro, 10 nM TCDD exposure suppressed splenocyte adhesion. In addition,
      the adhesiveness was reduced after in vivo exposure to TCDD (15 microg/kg) for
      six weeks with a one week interval and after additional in vitro stimulation with
      anti-CD3. The inhibition of adherence after TCDD exposure was related to a
      decreased expression of LFA-I, and expression patterns of Rap1 following TCDD
      exposure correlated with those of LFA-1 expression. However, TCDD did not
      selectively alter LFA-1 or Rapl expression in T-cell subsets. TCDD caused
      apparent changes in PI 3-kinase expression levels and the expression patterns of
      H-Ras correlated with those of PI 3-kinase expression. These data suggest that
      TCDD exposure down-regulates the conformation and ligand binding affinity of LFA
      1 by Rapl and PI 3-kinase signaling pathways with the decreased expression of LFA
      1, and consequently leads to a decrease in the LFA-1-mediated adhesion.

PMID- 17201181
TI  - Adjuvant electrochemotherapy for the treatment of incompletely resected canine
      mast cell tumors.
AB  - BACKGROUND: Electrochemotherapy (ECT) is a novel anticancer therapy that combines
      the delivery of trains of appropriate waveforms with the local administration of
      chemotherapy agents. The purpose of this investigation was to assess the adjuvant
      potentials of ECT for the treatment of incompletely excised mast cell tumors
      (MCT). MATERIALS AND METHODS: Twenty-eight privately-owned dogs with incompletely
      removed MCT were treated with intralesional bleomycin (1.5 IU/cm2) followed by
      the application of trains of biphasic pulses (8 pulses, 1300 V/cm, 50 + 50 micros
      duration, 1 Hz frequency). RESULTS: The overall response rate was 85% with a mean
      estimated time to recurrence of 52.76 +/- 6.5 months (range: 39.99 to 65.54
      months, 95% CI). At the time of writing this report, the median survival time was
      not reached. Three dogs died of metastatic disease that they developed at the
      same time of local recurrence, one developed multiple cutaneous nodules at
      different locations and one with recurrence was re-treated and is currently
      disease-free after 22 months. No major local or systemic toxicities were noted
      for the duration of the study. CONCLUSION: ECT is a safe and effective therapy
      for incompletely excised MCTs in companion animals. Its ease of administration,
      lack of toxicities and low cost make it an attractive alternative to standard
      treatments and warrants further investigation.

PMID- 17201182
TI  - T lymphocyte cytokine production patterns in hashimoto patients with elevated
      calcitonin levels and their relationship to tumor initiation.
AB  - The aim of the study was to evaluate the possible changes in CD4+ and CD8+ T-cell
      cytokine production patterns in Hashimoto's thyroiditis (HT) with elevated
      calcitonin (CT). Fourteen consecutive patients with verified HT were included in
      the present study. Patients were divided into two groups. Group I: 7 HT patients
      with elevated CT levels (>10 pg/ml); Group II: 7 HT patients with CT levels <10
      pg/ml). All patients underwent intracellular cytokine detection in CD4+ and CD8+
      T-cells of peripheral blood mononuclear cells (PBMC) by flow cytometry. Patients
      with elevated CT levels (group I) had significantly higher percentages of CD8+
      cells producing IFN-gamma compared to healthy donors. A detailed analysis of
      cytokine production patterns revealed that this was accompanied by an increased
      frequency of single IFN-gamma positive cells, i.e., cells not expressing most of
      the other cytokines tested. Similarly, patients in group I also showed higher
      percentages of CD8+ TNF-alpha positive cells than healthy donors. In this case,
      cells co-expressing TNF-alpha and IFN-gamma were found at significantly higher
      frequencies. No increase in Th1 type cytokines, such as IFN-gamma or TNF-alpha,
      was detectable in CD4+ T-cells. In contrast, CD4+ T-cells from group I patients
      showed significantly higher percentages of cells producing Th2 cytokines, such as
      IL-4 or IL-13. The lack of increased Th1 cytokine production accompanied by an
      increased Th2 cytokine production seems to be a special feature of HT patients
      with elevated CT levels that may reflect a pathogenetic mechanism for tumor
      initiation.

PMID- 17201183
TI  - Cyclin D1 and MLH1 levels in laryngeal cancer are linked to chromosomal
      imbalance.
AB  - BACKGROUND: Carcinogenesis results from the accumulation of genetic alterations
      forming a functional network leading to genetic instability as a cardinal
      feature. Thus, the hypothesis that down-regulation of MLH1 in combination with
      aberrant cell cycle control may contribute to chromosomal instability in LSCC was
      tested. PATIENTS AND METHODS: Fifty-two patients, diagnosed with primary LSCC,
      none of whom had a history of hereditary cancer, were evaluated by comparative
      genomics. The expression of selected proteins controlling the cell cycle and
      mismatch repair was assessed with immunostaining. RESULTS: In our set, 1720
      chromosomal imbalances were found, as well as altered protein synthesis including
      a decrease in RB1 and CDKN2A (10.2% and 44% of cases, respectively), an increase
      in CCND1 (47%) and a decrease in MLH1 (22.7%). Variation analysis correlating
      proteins, chromosomal imbalances and clinicohistopathological features of disease
      disclosed an association between chromosomal gains, low histopathological grade
      of tumour and CCND1 over-expression accompanied by a decrease in MLH1 expression
      (p < 0.01). CONCLUSION: CCND1 and MLH1 seem functionally interconnected in regard
      to chromosomal imbalances in larynx cancer.

PMID- 17201184
TI  - Treatment of peritoneal carcinomatosis using carboplatin-loaded hydroxyapatite
      particles.
AB  - The anti-tumor effects and tissue distribution of carboplatin (CBDCA)
      incorporated into hydroxyapatite (HAP) particles was studied. MATERIALS AND
      METHODS: Seven days after the intraperitoneal (i.p.) implantation of AH130 tumor
      cells into Donryu rats, the animals were randomized into four groups: group I was
      treated with saline i.p.; Group II, with CBDCA i.v.; group III with CBDCA i.p.;
      and group IV with HAP-CBDCA i.p. RESULTS: The survival rate of group IV was
      better than that of the other groups (p < 0.05). The area under the ascitic
      platinum concentration-time curve and tissue concentrations of platinum in the
      omentum after 24 hours of treatment were higher in group IV than in groups II or
      III (p < 0.05). The platinum concentrations in the kidneys of group IV were lower
      than in group III (p < 0.05). CONCLUSION: The HAP-CBDCA combination enhances the
      anti-tumor effects of the drug and reduces the nephrotoxicity in rats with
      peritoneal carcinomatosis.

PMID- 17201185
TI  - Influence of interleukin-6 on the invasiveness of human colorectal carcinoma.
AB  - BACKGROUND: Plasma interleukin-6 (IL-6) level correlates with patient survival in
      colorectal carcinoma and is regarded as a prognostic factor. In this study, the
      role of IL-6 in colorectal carcinoma proliferation, chemotaxis and invasion was
      investigated. MATERIALS AND METHODS: Proliferation and invasion were measured in
      four colorectal carcinoma cell lines. The effect of IL-6 (10, 50, 100 ng/ml) on
      progression (the ability to grow, adhere, chemotax and invade) was also measured.
      RESULTS: Physiological (10 ng/ml) and pharmacological (50 and 100 ng/ml)
      concentrations of IL-6 did not significantly affect growth. However, IL-6 (10
      ng/ml) significantly increased attachment to basement membrane (p < 0.05). IL-6
      (50 ng/ml) significantly increased the chemotaxis, anchorage-independent growth
      and invasiveness of SW-480 (one of the four cell lines) (p < 0.05). IL-6 (100
      ng/ml) resulted in negative feedback inhibition of these effects. CONCLUSION: IL
      6 plays an important role in the progression of colorectal carcinoma.

PMID- 17201186
TI  - Gonadotropin-releasing hormone analogues alter gene expression of
      metalloproteinases and their tissue inhibitors in human breast cancer epithelial
      cells.
AB  - Luteinizing hormone-releasing hormone (LHRH or GnRH) is not only produced by
      hypothalamus, but also by other normal and cancer tissues. GnRH peptide agonists
      and antagonists inhibit the proliferation of breast cancer cells, but their
      effect on the expression of metalloproteinases (MMPs) and their tissue inhibitors
      (TIMPs) has not been studied despite the fact that growth and invasiveness of
      breast cancer cells in adjacent and distant sites is associated with the
      expression of MMPs. In the present study, the effects of [D-Leu6, desGly10]GnRH
      NHEt (commercially available) and [D-Tic3, Deg6, desGlyl0]GnRH-NHEt on gene
      expression of MMPs and TIMPs in the breast cancer cell line MCF-7 were examined
      with semi-quantitative RT-PCR. Results showed that incubation of MCF-7 cells with
      30 microM of the synthetic GnRH analogues for 48 h in serum-containing medium
      resulted in a decrease of MMP-9 expression and increase in MT1- and MT2-MMP mRNA
      levels. Furthermore, both synthetic analogues induced a significant decrease in
      TIMP-1 and TIMP-3 mRNA levels and increase in TIMP-2 mRNA levels. The impact of
      the observed changes on the expression of MMPs and TIMPs warrants further
      investigation on the effects of GnRH analogues on the invasiveness and metastatic
      potential of breast cancer cells.

PMID- 17201188
TI  - Functional analysis and case-control study of -160C/A polymorphism in the E
      cadherin gene promoter: association with cancer risk.
AB  - BACKGROUND: A C-->A polymorphism within the CDH1 (E-cadherin) promoter seems to
      be associated with a reduced efficiency of gene transcription in vitro. Due to
      the crucial role of E-cadherin in epithelia, tissue-specific effect of C-->A
      change on CDH1 transcription was tested and a case-control study was performed on
      patients affected with epithelial tumors. PATIENTS AND METHODS: The -178/+93 CDH1
      region containing either C or A nucleotide was inserted upstream of the
      Luciferase reporter gene in the pGL-2 vector, and the construct activity was
      assessed by transient transfection assay in HeLa and HCT116 cells. RESULTS: A
      significantly lower activity for pGL-2A was found compared to pGL-2C, both in
      HeLa (54% decrease) and in HCT116 (67% decrease) cells. Genotyping of 246
      controls and 505 patients affected with breast, gastric, colorectal, cervical and
      endometrial cancers demonstrated an association between the A allele and an
      increased risk of colorectal, gastric and endometrial tumors (1.66-, 1.81- and
      2.35-fold, respectively). CONCLUSION: Our data support the notion that the A
      allele may act as a low-penetrance cancer susceptibility gene.

PMID- 17201187
TI  - In situ analysis of doxorubicin uptake and cytotoxicity in a 3D culture model of
      human HT-1080 fibrosarcoma cells.
AB  - In solid tumors, chemotherapeutics must adequately diffuse through the
      extracellular compartment to achieve their cytotoxic effect. Using quantitative
      microspectrofluorometry, both Doxorubicin penetration through three-dimensional
      (3D) collagen I matrices and its subsequent intranuclear accumulation into HT
      1080 cells cultured in this microenvironment were directly assessed. Evidence
      that collagen delayed the Doxorubicin penetration for 1 h is presented. During
      that period, drug concentrations were lower in the nuclei in 3D compared to 2D
      matrices. Anthracyclines were also found to exhibit similar cytotoxicity in 2D
      and 3D after long term incubation. In conclusion, in this 3D culture model,
      collagen type I matrices delayed the early distribution of low molecular weight
      therapeutics and failed to affect their long-term cytotoxic effects, as
      previously reported. This model may provide a rationale for avoiding the
      emergence of intrinsic chemoresistance in tissue.

PMID- 17201189
TI  - Expressed emotion: a review of assessment instruments.
AB  - Expressed emotion (EE) refers to the quality of the emotional climate between a
      relative and a family member with a serious psychiatric disorder. Well
      established, it has proven to be a reliable predictor of the relapse rate of
      psychiatric patients. In this article, the Camberwell Family Interview (CFI), the
      standard instrument, and 11 alternative EE measures will be presented and
      discussed with regard to their psychometric properties. It is concluded that the
      CFI remains the best instrument for assessing the quality of the relationship.

PMID- 17201190
TI  - Foundations of psychosocial dynamic personality theory of collective people.
AB  - The concept of personality emerged as a part of the development of individualism
      in the western world to understand the quality of the newborn (individual). In
      premodern society, roles were the elements that constituted the person.
      Presently, about 80% of the people (Africa, Asia, and South America) in the world
      still live in a collective, authoritarian system. Personality theories that have
      been developed in Europe and North America seem to be limited in understanding
      and predicting the behavior of these people. One major difference between
      individualistic and collective peoples is their degree of individuation from the
      family. Western social-political systems enable individuals at the end of their
      development course to form an independent personality (or self) that is unique
      and different from others. For westerners, personality structures and processes
      enable us to predict behavior. Psychopathology is attributed to an intrapsychic
      disorder within the personality. Typically, psychotherapy aims to restore that
      order. For people who live in collective social systems, individuation does not
      take place. Therefore, norms, values, roles, and familial authority directives
      predict behavior more than personality. Psychopathology among these people has to
      do with interpersonal disorder within the family. Therefore, psychotherapy should
      aim to restore that order. This manuscript suggests foundations of a new
      psychosocial dynamic theory of personality to better fit our understanding of
      people living in collective societies.

PMID- 17201191
TI  - Psychotherapy and social support: integrating research on psychological helping.
AB  - Psychotherapy interactions and social support conversations have many
      similarities, as well as some important differences. Researchers studying these
      two manifestations of psychological helping--often known as formal and informal
      helping--usually apply a separate set of concepts and methods to each and tend to
      locate their work in separate bodies of literature. This paper argues that such a
      division of the field is unnecessary and unproductive. It outlines several ways
      in which the two bodies of literature might inform each other and argues for
      conceptual integration of the two fields.

PMID- 17201192
TI  - Social support interventions: do they work?
AB  - Presence of support has repeatedly been linked to good long-term health outcomes
      based on demonstrations of better immune function, lower blood pressures, and
      reduced mortality (among others). Despite a massive literature on the benefits of
      support, there is surprisingly little hard evidence about how, and how well,
      social support interventions work. Using a computerized search strategy, 100
      studies that evaluated the efficacy of such interventions were located. The
      presenting problems ranged from cancer, loneliness, weight loss, and substance
      abuse to lack in parenting skills, surgery, and birth preparation. For the
      purpose of review and evaluation, studies were subdivided into (1) group vs.
      individual interventions, (2) professionally led vs. peer-provided treatment, and
      (3) interventions where an increase of network size or perceived support was the
      primary target vs. those where building social skills (to facilitate support
      creation) was the focus. On the whole, this review provided some support for the
      overall usefulness of social support interventions. However, because of the large
      variety of existing different treatment protocols and areas of application, there
      is still not enough evidence to conclude which interventions work best for what
      problems. Specific methodological and conceptual difficulties that plague this
      area of research and directions for future research are discussed.

PMID- 17201193
TI  - Neuropsychological consequences of HIV in children: a review of current
      literature.
AB  - Pediatric HIV has reached epidemic proportions. In 1997, 1.1 million children
      younger than 15 were living with HIV or AIDS. The virus affects children
      cognitively and developmentally due to the immaturity of their nervous systems
      and immune systems. Studies in the area of neuropsychological deficits are as yet
      limited in number and less well developed than studies on adult HIV. However,
      despite methodological weaknesses, the literature has proven conclusively that
      pediatric HIV affects children cognitively, developmentally, emotionally,
      psychologically, behaviorally, and educationally. Although treatments are
      allowing these children to live longer, the effects of the virus remain,
      requiring special care. This review examines the mechanisms behind HIV in
      children, the neuropsychological findings to date, and the limitations of this
      work. Possible useful future approaches in understanding the neuropsychological
      course of the disorder, as well as directions for treatment and prevention are
      addressed.

PMID- 17201194
TI  - Bilingualism, brain injury, and recovery: implications for understanding the
      bilingual and for therapy.
AB  - Psychologists and other therapists are seeing an increasingly large number of
      bilingual individuals. Such clients are a special challenge when there has been
      some type of brain injury or disease because of the seemingly unpredictable
      effect such disorders may have on language skills, impacting either or both of
      the client's languages and interfering with internal speech that plays a role in
      higher cognitive functions such as insight and awareness. While there are many
      clinical assumptions about which language will show the least impairment or
      recover the best, such suppositions based on clinical lore are often
      contradictory. A review of the literature finds that the outcome of brain injury
      may be influenced by factors such as cerebral representation of a secondary
      language, method of language acquisition, age of acquisition, premorbid language
      proficiency, and style of learning in an individual. Neuropsychological concepts
      that can explain these findings are examined, along with their implications for
      therapy, and rehabilitation.

PMID- 17201195
TI  - Development of ELISA to detect antibodies specific to Mycobacterium avium subsp.
      paratuberculosis with truncated 34 kDa proteins.
AB  - To develop ELISA to detect antibodies specific to Mycobacterium avium subsp.
      paratuberculosis (M. paratuberculosis), the carboxyl termini of the 34 kDa
      proteins of M. paratuberculosis and Mycobacterium avium subsp. avium (M. avium)
      were expressed in Escherichia coli expression system. Antibodies specific to M.
      paratuberculosis were detected with the truncated 34 kDa protein of M.
      paratuberculosis in ELISA after pre-absorption of serum samples with the
      truncated 34 kDa protein of M. avium. All the serum samples from cattle confirmed
      to be infected with M. paratuberculosis were positive and those from healthy
      cattle were negative in the present ELISA system. These results indicate that the
      established ELISA detects antibodies specific to M. paratuberculosis with high
      specificity and sensitivity and is an useful tool for the screening of Johne's
      disease.

PMID- 17201196
TI  - Seroepidemiological survey of morbillivirus infection in Kuril harbor seals
      (Phoca vitulina stejnegeri) of Hokkaido, Japan.
AB  - Serological analysis was performed to detect morbillivirus infection in Kuril
      harbor seals in Hokkaido, Japan. Serum samples were collected from the seals at
      Nosappu (231 sera), Akkeshi (16), and Erimo (75) between 1998 and 2005.
      Antibodies to phocine distemper virus (PDV) were detected by ELISA in seals from
      Nosappu and Erimo. Antibodies to PDV were found in 56% (5/9) of the sampled seals
      from Nosappu in 1998, versus only 5% (3/66) for 2003, 1% (1/79) for 2004, and 1%
      (1/77) for 2005. These suggest epidemic caused by the virus in or before 1998. As
      antibody-positive seals included juvenile seals in 2003 and 2005, sporadic
      infections of the virus are thought to have occurred in recent years. In Erimo,
      antibodies to PDV were found in 50% (14/28) of sampled seals in 2004, versus only
      13% (1/8) for 1999, 7% (1/15) for 2003, and 0% (0/24) for 2005. These suggest
      sporadic infection by the virus before 2003 and the epizootic between after
      autumn in 2003, when samples of 2003 were collected, and 2004. Since antibodies
      to canine distemper virus (CDV) were detected in one adult seal from Nosappu in
      each year from 2003 to 2005, sporadic infections of the virus were suggested.
      There were no difference in incidence of seals with antibodies to the viruses
      between males and females and between juveniles and adults.

PMID- 17201197
TI  - Pesticide/herbicide pollutants in the Kafue River and a preliminary investigation
      into their biological effect through catalase levels in fish.
AB  - The study determined the types of pesticide/herbicide pollutants in water,
      sediment and fish from the Kafue River. A preliminary investigation of the
      oxidative stress from these pesticides/herbicides was also assessed by
      measurement of catalase activity. Water, sediment and fish samples were collected
      upstream, midstream and downstream the Kafue river in Chingola, Kitwe, Kafue
      National Park and Kafue Town. Water, sediment and fish muscle were sampled and
      analysed for pesticides using Gas chromatography. For catalase activity fish
      liver samples only were examined. The pesticides/herbicides detected in all
      samples collectively included: Heptachlor, pp'-DDE, Cypermethrin, Chlordane,
      Toxaphene, Terbufos, Kelthane, Endosulfan, Dieldrin, pp'-DDD, pp'-DDT, Atrazine,
      Disulfoton, d-trans-Allethrin and Endrin. On the other hand, catalase activity
      was detected in all fish liver samples from all sites. Its levels increased
      significantly from Chingola upstream to sites downstream with highest being in
      Kafue town. This study therefore, demonstrates that there is widespread
      contamination of the Kafue River with pesticides/ herbicides. It also
      demonstrates that organochlorides are found throughout the river especially in
      fish samples. The spectrum of pesticides/herbicides was much wider in fish
      probably due to bioaccumulation. It was also observed that fish are subjected to
      oxidative stress as determined by catalase levels. The stress is more pronounced
      downstream where the catalase levels were significantly higher than Chingola. The
      observation that more pesticide varieties are also found downstream may suggest a
      likely causative effect of the pesticides on oxidative stress although this needs
      further investigation. This study further tentatively highlights the potential
      dangers of these agro-related substances to dependants of the Kafue River water
      body and the need to carry out risk assessments and thereafter institute
      corrective measures to help reduce contamination and adverse effects.

PMID- 17201198
TI  - The prevalent genotypes of bovine viral diarrhea virus in Japan, Germany and the
      United States of America.
AB  - Genotypes and subgenotypes of bovine viral diarrhea virus (BVDV) field isolates
      from Japan, Germany and the United States of America (USA) were identified, and
      the prevalent pattern of BVDV in individual countries was estimated genetically.
      Subgenotypes were determined based on phylogenetic analyses of nucleotide
      sequences of a part of the E2-coding gene of BVDV. Forty-five, 61 and 56 BVDV
      strains were isolated from naturally infected cattle in Japan, Germany and USA,
      respectively, between 1980 and 2003. The most prevalent BVDV in these three
      countries was BVDV-1b. The second most prevalent BVDV strains were 1a, 1d and
      BVDV-2 in Japan, Germany and USA, respectively. The most prevalent subgenotype 1b
      in each country constructed individual small clusters in the subgenotype 1b
      branch in the phylogenetic tree. Although cattle and/or cattle products were
      moving among the three countries as part of international trade, the distribution
      of BVDV in the field in each country showed long-standing individual patterns.

PMID- 17201199
TI  - Possible conservation units of the sun bear (Helarctos malayanus) in Sarawak
      based on variation of mtDNA control region.
AB  - The mitochondrial DNA control region of the sun bear (Helarctos malayanus) was
      sequenced using 21 DNA samples collected from confiscated sun bears to identify
      conservation units, such as evolutionarily significant units and management
      units, in Sarawak, Borneo Island. A total of 10 haplotypes were observed,
      indicating the presence of at least two lineages in the sun bear population in
      Sarawak. Presumably, these two lineages could represent evolutionarily
      significant units. However, the geographical distributions of the two lineages
      remained unknown due to the lack of information regarding the exact capture
      locations of the confiscated sun bears. It is essential to elucidate the
      geographical distributions of these lineages in order to create a proper
      conservation plan for the sun bears in Sarawak. Therefore, further studies
      examining the haplotype distributions using DNA samples from known localities are
      essential.

PMID- 17201201
TI  - Accelerated detection of extended-spectrum beta-lactamases in clinical isolates
      of Enterobacteriaceae.
AB  - A prospective study is carried out to evaluate the performance of a protocol for
      the accelerated detection of extended-spectrum beta-lactamases (ESBLs) in
      clinical isolates of Escherichia coli, Klebsiella pneumoniae and other Gram
      negative bacteria. A modified double-disc test (MDDT) is incorporated in a Gram
      negative template for routine susceptibility testing. The MDDT identified
      accurately ESBLs in all isolates subsequently confirmed as ESBL-producers by the
      standard Clinical Laboratory Standards Institute (CLSI) combined disc method. Of
      1213 isolates tested, 98 (8%) were positive for ESBLs by MDDT and 95 (7.8%) were
      positive by the CLSI method. ESBLs were detected in 48 (7.8%) E. coli, 21 (8%) K.
      pneumoniae, 12 (5.8%) Proteus mirabilis, 13 (18.8%) Providencia stuartii and four
      (6.8%) Enterobacter cloacae isolates. Time required for ESBL detection by the
      MDDT method was one day. The protocol described provides a simple, rapid and low
      cost method for early detection of ESBLs in Gram-negative bacteria.

PMID- 17201200
TI  - Summary health statistics for U.S. children: National Health Interview Survey,
      2005.
AB  - OBJECTIVES: This report presents both age-adjusted and unadjusted statistics from
      the 2005 National Health Interview Survey (NHIS) on selected health measures for
      children under 18 years of age, classified by sex, age, race, Hispanic origin,
      family structure, parent education, family income, poverty status, health
      insurance coverage, place of residence, region, and current health status. The
      topics covered are asthma, allergies, learning disability, Attention Deficit
      Hyperactivity Disorder (ADHD), prescription medication use, respondent-assessed
      health status, school-loss days, usual place of health care, time since last
      contact with a health care professional, selected measures of health care access
      and utilization, and dental care. SOURCE OF DATA: NHIS is a multistage
      probability sample survey conducted annually by interviewers of the U.S. Census
      Bureau for the Centers for Disease Control and Prevention's National Center for
      Health Statistics and is representative of the civilian noninstitutionalized
      population of the United States. Data are collected for all family members during
      face-to-face interviews with adults present at the time of interview. Additional
      information about children is collected for one randomly selected child per
      family in face-to-face interviews with an adult proxy respondent familiar with
      the child's health. SELECTED HIGHLIGHTS: In 2005, most U.S. children under 18
      years of age had excellent or very good health (82%). However, 9% of children had
      no health insurance coverage, and 5% of children had no usual place of health
      care. Thirteen percent of children had ever been diagnosed with asthma. An
      estimated 7% of children 3-17 years of age had a diagnosed learning disability,
      and an estimated 7% of children had ADHD.

PMID- 17201202
TI  - Better diagnosis and treatment of throat infections caused by group A beta
      haemolytic streptococci.
AB  - This study aims to assess the diagnostic value of a rapid streptococcal antigen
      test in addition to four clinical features in patients with sore throat, using
      throat culture and antibody titre as reference tests, and to evaluate the
      efficacy of the current antibiotics used in the treatment of throat infections
      caused by group A beta-haemolytic streptococcus (GABHS). Four clinical features
      (fever [history of] > or = 38 degrees C, lack of cough, tonsillar exudate, and
      anterior cervical lymphadenopathy) are recorded in 355 patients aged four years
      to > or =15 years. A rapid antigen diagnostic test (RADT) is performed, as well
      as a throat culture. Antistreptolysin O (ASO) titre is performed in patients 11
      years. GABHS from patients are tested for susceptibility to different
      antibiotics. Throat cultures were positive for GABHS in 19% patients. Rapid tests
      were positive in 24%. Compared with throat culture, the rapid test gave a
      sensitivity of 91%, specificity of 91%, positive predictive value of 73% and a
      negative predictive value of 98%. For patients with three or four clinical
      features, however, the sensitivity was considerably higher at 97%. Using the ASO
      test as a reference, no association was found between RADT and culture results.
      Zithromax showed the highest prescription rate (25.5%) and produced a high cure
      rate (91%) in patients with GABHS pharyngitis.

PMID- 17201203
TI  - Comparison of biopsy-based methods for the detection of Helicobacter pylori
      infection.
AB  - Various biopsy-based methods for the detection of Helicobacter pylori are
      evaluated to determine their sensitivity, specificity, positive predictive value
      (PPV) and negative predictive value (NPV), followed by polymerase chain reaction
      (PCR) for the 16S ribosomal RNA (rRNA) gene of H. pylori (16S PCR) to confirm the
      results. Seventyfive patients (65% [49] males, age range: 17-77 years, mean 42+/
      14.6 years) with dyspeptic symptoms are included in the study. Gastric antrum
      biopsy specimens collected during endoscopy are tested using a urea agar base
      enriched with 40% urea solution (eUAB, Oxoid)), a commercial rapid urease test
      (Pronto Dry, Medical Instrument Corp, Switzerland), histopathology and 16S PCR.
      The eUAB test showed 97% sensitivity, 86% specificity, 84% PPV, 97% NPV and 91%
      accuracy when the diagnosis of H. pylori infection was made with positive Pronto
      Dry and histopathology. Pronto Dry showed 100% sensitivity, 82% specificity, 80%
      PPV, 100% NPV and 89% accuracy when the diagnosis of H. pylori infection was made
      on positive histopathology and eUAB. Thus, the eUAB can be used as a rapid urease
      test. It is economical and has a sensitivity and specificity comparable to a
      commercially available rapid urease test to detect urease activity of H. pylori
      in gastric biopsy.

PMID- 17201204
TI  - Young adult reference ranges for thyroid function tests on the Centaur
      immunoassay analyser.
AB  - This study aims to establish reference ranges for thyroid tests in young Saudi
      adults using the Centaur immunoassay method. Physical examination is performed
      and thyroid function tests include thyroid stimulating hormone (TSH), free
      thyroxine (FT4) and free triiodothyronine (FT3). These are performed on 291 young
      Saudi adults (182 [63%] females and 109 [37%] males; average age: 27 years [range
      18-50]). Clinical thyroid abnormality, related symptoms and/or abnormal thyroid
      function tests exclude a person from the study and thus a total of 276 subjects
      (171 [62%] females and 105 [38%] males) are used to establish the new reference
      ranges. Combined female and male ranges for TSH, FT4, and FT3 were found to be
      0.48-6.30 miu/L (9.00-18.62 pmol/L and 3.39-6.85 pmol/L, respectively). Mean TSH
      and FT4 levels were significantly different (P<0.0001) from those quoted by the
      manufacturer. Ranges for TSH were 0.48-6.30 miu/L (female) and 0.52-4.89 miu/L
      (male) (P=0.08). Female ranges for FT4 and FT3 were 9.00-17.15 pmol/L and 3.39
      5.82 pmol/L, respectively. Male ranges were 9.92-18.62 pmol/L (P=0.0001) and 4.36
      6.85 pmol/L (P<0.0001). The range of TSH levels in the young local Saudi
      population proved to be higher than that quoted by the manufacturer. FT4 range
      was lower and narrower than that quoted by the manufacturer. Significant
      differences between female and male populations suggest that partitioning of the
      reference ranges by gender is necessary.

PMID- 17201205
TI  - Role of leucocytes in damage to the vascular endothelium during ischaemia
      reperfusion injury.
AB  - During this investigation, a model of tourniquet-induced forearm ischaemia
      reperfusion injury is employed to investigate the role of leucocytes in damage to
      the vascular endothelium during ischaemia-reperfusion injury. Leucocyte
      entrapment is investigated by measuring the concentration of leucocytes in venous
      blood leaving the arm. Neutrophil and monocyte leucocyte subpopulations are
      isolated by density gradient centrifugation techniques. Cell surface expression
      of CD11b and the intracellular production of hydrogen peroxide are measured via
      flow cytometry. Plasma concentrations of elastase and von Willebrand factor (vWF)
      are measured using enzyme-linked immunosorbemt assay (ELISA) techniques. During
      ischaemia-reperfusion, there was an increase in CD11b cell surface expression on
      neutrophils (P=0.040) and monocytes (P=0.049), and a decrease in peripheral blood
      leucocytes (P=0.019). There was an increase in the intracellular production of
      hydrogen peroxide by leucocyte subpopulations (P=0.027 [neutrophils], P=0.091
      [monocytes]) and in the plasma elastase concentration (P=0.05). There was also a
      trend to increasing plasma concentration of vWF (P=0.0562), which was measured as
      a marker of endothelial damage. Ischaemia-reperfusion results in increased
      adhesiveness, entrapment and activation of leucocytes. Even following a mild
      ischaemic insult, this leucocyte response was followed immediately by evidence of
      endothelial damage. These results may have important implications for
      understanding the development of chronic diseases that involve mild ischaemic
      episodes.

PMID- 17201206
TI  - Combined use of honey, bee propolis and myrrh in healing a deep, infected wound
      in a patient with diabetes mellitus.

PMID- 17201207
TI  - Interleukin (IL)-1beta, IL-6 and IL-8 in nasal secretions: a common role for
      innate immunity in viral bronchial infection in infants?

PMID- 17201208
TI  - Role of interleukin-1beta and tumour necrosis factor-alpha on hydroxyapatite
      induced phagocytosis by murine macrophages (RAW264.7 cells).

PMID- 17201209
TI  - Genetic heterogeneity of the cytolethal distending toxin B (cdtB) gene locus
      among isolates of Campylobacter lari.

PMID- 17201210
TI  - Molecular diagnosis of native mitral valve endocarditis due to Corynebacterium
      striatum.

PMID- 17201211
TI  - Immune-mediated paraneoplasia.
AB  - Cancers induce a loss of homeostasis through the uncontrolled production and
      release of a variety of biologically active cellular products, natural compounds
      produced in unnatural quantities within abnormal anatomical locations. Often,
      there is an immune response to which the cancerous growth may succumb, or have
      the characteristics required to survive. If, during its proliferation, the cancer
      should coincidentally express a potent autoantigen then the organ in which that
      antigen is normally located may be damaged by the resultant immune response.
      Paradoxically, this aberrant immunological activity rarely has any appreciable
      inhibitory effects on the causal cancer. This inconsistency may result from the
      cancer's ability to block the host's immunological activity, while the affected
      organ situated elsewhere has no such capacity. Some predisposition, such as
      trauma to the affected organ, may prove a prerequisite that provides access to
      hitherto immunologically privileged sites. The effects of the subsequent loss of
      tolerance are often the first indication of a health problem, prompting the
      patient to seek medical help. Immune-mediated paraneoplasia is identified by
      antibody activity with any of a small but growing collection of organ-specific
      antigens demonstrated to have a distinct disease association and an apparent
      involvement in autoimmunity. Examples of the most common are described as
      introduction to this unusual collection of autoimmune diseases, for which in some
      cases the cause is known, and these may provide insight into the cause of those
      that are not.

PMID- 17201212
TI  - [Some problems of state regulation in sanatorium and resort service].

PMID- 17201213
TI  - [Electric impulse therapy of hypertensive patients].
AB  - Patients with mild arterial hypertension and hypersympathicotonia treated with
      electroimpulse therapy improved their clinicofunctional state, blood pressure
      (especially systolic pressure), its variability, sympathic activity, central
      regulation of cardiac rhythm, capillary reserves.

PMID- 17201214
TI  - [Electrostimulation of the skeletal muscles in sanatorium rehabilitation of
      patients with myocardial infarction].
AB  - Passive physical training with ESMA device was used in rehabilitation of 81 men
      with complicated myocardial infarction treated in sanatorium Taraskul. The
      training had no negative clinical and hemodynamic reactions, increased exercise
      tolerance, reduced volume of heart chambers, aggravated neither arrhythmia nor
      autonomic imbalance. This method of physical training is recommended if standard
      rehabilitative programs are impossible.

PMID- 17201215
TI  - [Correction of free radical processes in patients with ischemic heart disease
      using bicycle exercise with free choice of load].
AB  - The aim of the study was to examine changes in the system lipid peroxidation
      antioxidant defense (LPO-AOD) in patients with ischemic heart disease (IHD)
      exercising on the bicycle in free load regime. A course of standard medication in
      IHD patients reduced the level of lipid peroxidation by 15.1% (p < 0.05), on the
      average, malonic dialdehyde (MDA)--by 21.4% (p < 0.05), but at the end of the
      treatment these parameters did not reach those of healthy subjects and remained
      higher than they had. The addition of bicycle exercise in the treatment reduced
      LPO to the level of healthy subjects. AOD also changed in trained IHD patients:
      catalase activity rose in the trained patients by 22.6% (p < 0.001), on the
      average, that of superoxide dismutase--by 19.0% (p < 0.05). Total antioxidant
      activity of erythrocytes in trained patients rose by 24.0% (p < 0.01), total
      antioxidant activity of plasma increased by 43.3%. Thus, free bicycle exercise
      raises antiradical potential of blood in IHD patients. The effect of the exercise
      was the highest on the enzymes of AOD system.

PMID- 17201216
TI  - [The role of the stabilogram biocontrol method in walking function recovery in
      patients with poststroke hemipareses].
AB  - Effects of stability training (ST) with the method of biocontrol by stabilogram
      on walking function were studied in 32 patients with poststroke hemipareses with
      the disease duration from 1 month to 2 years. The findings evidence that
      biofeedback by stabilogram has a positive effect not only on static and dynamic
      stability of patients with poststroke hemiparesis but also on functional mobility
      of the patients. It improves such important gait characteristics as speed, length
      and symmetry of the step.

PMID- 17201218
TI  - [Intensive physical conditioning as nonspecific prophylaxis of respiratory
      diseases in children].
AB  - We studied efficacy of using intensive physical conditioning as prophylaxis of
      respiratory diseases in young children and health status of children exposed to
      physical conditioning in childhood (a total of 44 children aged from 1.5 months
      to 1 year; 58 children aged from 2.5 to 13.5 years). The proposed method of
      conditioning significantly diminished incidence of respiratory infections,
      enhanced local immunity of the upper respiratory tract and prevented development
      of chronic diseases at later age.

PMID- 17201217
TI  - [Aeroionotherapy in prevention of acute respiratory diseases in children].
AB  - Our studies show pathogenetic validity of using biocontrolled aeroionotherapy in
      children often having acute respiratory infections. A course impact of negative
      aeroions corrected functional disorders in children, reduced frequency of acute
      respiratory infections, durations of the illness.

PMID- 17201220
TI  - [The role of nutrition in maintenance of adaptive reserves and lowering the risk
      of stress disorders].

PMID- 17201219
TI  - [Efficacy of magnetotherapy in diabetic peripheral neuropathy in children].

PMID- 17201222
TI  - [Ozone therapy in gastroduodenal pathology associated with Helicobacter pylori].
AB  - Three methods of ozone therapy (intravenous injection of ozonized physiologic
      saline, oral intake of ozonized low-mineral water and combination of the two
      treatments) were compared by efficacy in 215 patients with gastroduodenal
      pathology associated with Helicobacter pilori. All the techniques of ozone
      therapy proved effective in relation to regress of clinical symptoms,
      regeneration processes, eradication of Helicobacter pylori, but the combined
      regimen was the best.

PMID- 17201221
TI  - [Magnesium-containing mineral waters in the treatment of patients with cardial
      manifestations of gastroesophageal reflux disease].
AB  - Drinking of sulphate-magnesium-calcium water by patients with gastroesophageal
      reflux disease of the first degree with cardial manifestations has a prokinetic
      and anti-inflammatory action leading to attenuation of gastroesophageal reflux
      and positive cardiovascular changes. Marked therapeutic efficacy of the water is
      due to specific action of magnesium ions having membrane-stabilizing, sedative
      effects, pronounced prokinetic and sympatholytic actions which manifest with
      weakening of ergotropic actions, higher efficacy of cardiac activity. These
      convert to a noticeable clinical response--regress of clinical symptoms and
      potentiation of anti-arrhythmic effects.

PMID- 17201223
TI  - [Interference currents in combined therapy of chronic pyelonephritis in
      children].
AB  - Investigations performed by the authors proved pathogenetic validity of
      interference therapy of chronic pyelonephritis in children. A course of
      interference currents has a positive effect on partial renal functions, excretion
      of beta2-microglobulin, urodynamics of the lower urinary tract, humoral and cell
      links of immunity, lipid peroxidation in red cell membranes. Advantages of
      interference currents impact on the reflex-segmentary zone and urinary bladder
      projection area in children with concomitant neurogenic dysfunction of the
      urinary bladder are shown.

PMID- 17201225
TI  - [Transcranial micropolarization in the treatment of specific speech disorders in
      children].
AB  - Efficacy of transcranial micropolarization (TCMP) was studied in the treatment of
      34 children aged 3-6 years with disorders of expressive speech (DES). The course
      of TCMP improved speech activity, increased active vocabulary and listening
      attention. Children who were able to use phrases in their speech used longer
      phrases after the therapy. The analysis of quantitative EEG demonstrated
      potentiation of alpha-rhythm power in the temporal and occipital areas,
      attenuation of the power in theta-band (4-8.5 Hz) in the central and frontal
      zones of the cortex after TCMP treatment.

PMID- 17201224
TI  - [Modulated low-frequency electrotherapy in patients with hyoid lipodystrophy].

PMID- 17201226
TI  - [Main principles of physiotherapy of copulative dysfunction in men].

PMID- 17201227
TI  - [Effects of physical factors on morphofunctional condition of cell cultures].

PMID- 17201228
TI  - [Differential administration of physical factors in correction of sex
      dysfunctions in athletes. Practice guideline for physicians].

PMID- 17201229
TI  - On the cover. Paper wasp.

PMID- 17201230
TI  - Selective IgM immunodeficiency: retrospective analysis of 36 adult patients with
      review of the literature.
AB  - OBJECTIVE: To review and compare previously reported cases of selective IgM
      immunodeficiency (SIgMID) with the largest adult cohort obtained from a
      retrospective analysis of an allergy and immunology practice. DATA SOURCES:
      Publications were selected from the English-only PubMed database (1966-2005)
      using the following keywords: IgM immunodeficiency alone and in combination with
      celiac disease, autoimmune disease, malignancy, and infection. Bibliographic
      references of relevant articles were used. STUDY SELECTION: Reported adult SIgMID
      cases were reviewed and included in a comparative database against our cohort.
      RESULTS: Previously described patients with SIgMID include 155 adults and 157
      patients of unspecified age. Thirty-six adult patients were identified with
      SIgMID from a database of 13,700 active adult patients (0.26%, 1:385). The mean
      +/- SD serum IgM level was 29.74 +/- 8.68 mg/dL (1 SD). The mean +/- SD age at
      the time of diagnosis of SIgMID was 55 +/- 13.5 years. Frequency of presenting
      symptoms included the following: recurrent upper respiratory tract infections,
      77%; asthma, 47%; allergic rhinitis, 36%; vasomotor rhinitis, 19%; angioedema,
      14%; and anaphylaxis, 11%. Serologically, 13% of patients had positive
      antinuclear antibodies (ANAs), 5% had serologic evidence of celiac disease, and
      nearly all had non-AB blood type. Patients also had low levels of IgM
      isohemagglutinins. No patients developed lymphoproliferative disease or
      panhypogammaglobulinemia, and none died of life-threatening infections,
      malignancy, or fulminant autoimmune-mediated diseases during a mean follow-up
      period of 3.7 years. CONCLUSIONS: The prevalence of SIgMID in our adult
      population was 0.26% and may be more common than previously thought. Non-life
      threatening respiratory disorders were common comorbid conditions.

PMID- 17201231
TI  - The expanding role of leukotriene receptor antagonists in chronic asthma.
AB  - OBJECTIVE: To provide a comprehensive review of studies that evaluate the effects
      of leukotriene receptor antagonists in adult chronic asthma. DATA SOURCES: A
      literature search using MEDLINE, Clinical Evidence, and the Cochrane Library was
      performed using the following keywords: randomized controlled trial, asthma,
      cysteinyl leukotriene, leukotriene receptor antagonist, antileukotriene,
      montelukast, zafirlukast, pranlukast, inflammation, lung function, exacerbations,
      and symptoms. STUDY SELECTION: Relevant peer-reviewed articles (mostly randomized
      controlled trials, meta-analyses, and reviews) published up to July 2006 were
      selected and extracted. RESULTS: Leukotriene receptor antagonists are beneficial
      across a range of asthma severities and may have a particular role in exercise
      induced asthma, aspirin-sensitive asthma, and individuals with concomitant
      allergic rhinitis. CONCLUSION: In the management of chronic asthma, leukotriene
      receptor antagonists have emerged as a useful oral nonsteroidal anti-inflammatory
      adjunct both as monotherapy and in combination with other classes of drugs.
      Monitoring their effects in terms of lung function alone may result in clinicians
      missing beneficial effects on inflammatory biomarkers, airway
      hyperresponsiveness, and exacerbations.

PMID- 17201232
TI  - Acoustic rhinometry in the practice of allergy.
AB  - OBJECTIVE: To provide a comprehensive practical overview of the use of acoustic
      rhinometry in the practice of allergy. DATA SOURCES: An all-inclusive PubMed
      search was conducted for articles on acoustic rhinometry that were published in
      peer-reviewed journals, between 1989 and 2006, using the keywords acoustic
      rhinometry, allergic rhinitis, and nasal provocation testing. STUDY SELECTION:
      The expert opinion of the authors was used to select studies for inclusion in
      this review. RESULTS: Acoustic rhinometry is a sound-based technique used to
      measure nasal cavity area and volume. It has been validated by comparison to
      measurements with computed tomography and magnetic resonance imaging. Acoustic
      rhinometry requires minimal patient cooperation and may be used in adults,
      children, and infants. It is used by medical practitioners to diagnose and
      evaluate therapeutic responses in conditions such as rhinitis and to measure
      nasal dimensions during allergen provocation testing. Acoustic rhinometry also
      provides a visual reflection of the nasal response to therapy, which may be
      useful in increasing compliance to prescribed medications. CONCLUSIONS: Acoustic
      rhinometry is a safe, noninvasive, objective, and validated measure of nasal
      obstruction that appears to be of practical use in the diagnosis and management
      of inflammatory diseases of the upper airways.

PMID- 17201233
TI  - Interleukin 7 receptor alpha-chain-mutation severe combined immunodeficiency
      without lymphopenia: correction with haploidentical T-cell-depleted bone marrow
      transplantation.
AB  - BACKGROUND: Severe combined immunodeficiency (SCID) is a rare primary
      immunodeficiency characterized by abnormal lymphocyte development and
      lymphopenia. It often presents during the first year of life with recurrent,
      opportunistic infections, failure to thrive, and malabsorption. OBJECTIVE: To
      advocate newborn screening for SCID. METHODS: We reviewed the case histories of
      dizygotic twins with Pneumocystis carinii pneumonia (PCP) at the age of 6 months.
      RESULTS: Full-term fraternal twin girls were born to nonconsanguineous parents.
      Twin A developed recurrent oral candidiasis at 2 months, followed by pneumococcal
      bacteremia and PCP. At 5 months she had failure to thrive, but her absolute
      lymphocyte count was normal (5,887 cells/mm3). Subsequently, twin B presented
      with acute respiratory distress and was also diagnosed as having PCP; her
      absolute lymphocyte count was 5,852 cells/mm3. Flow cytometric analysis of
      peripheral blood lymphocytes from both girls demonstrated a T-B+NK+ phenotype
      consistent with interleukin 7 receptor alpha-chain-mutation SCID. Both girls
      received a haploidentical T-cell-depleted bone marrow transplant from their
      mother. In the interim, a homozygous point mutation in the interleukin 7 receptor
      alpha-chain gene was identified in twin B. Both parents were found to be
      carriers. Twin A died of chronic lung disease 8 months after transplantation;
      twin B is currently thriving. CONCLUSIONS: Early diagnosis and treatment of SCID
      are associated with an increased rate of survival and improved long-term outcome.
      Some patients with SCID can present without lymphopenia. Thus, we advocate that
      more sensitive screening tests be considered for inclusion in the newborn
      screening program currently used in most states.

PMID- 17201234
TI  - Pectin anaphylaxis and possible association with cashew allergy.
AB  - BACKGROUND: Inhalation of pectin has been identified as a cause of occupational
      asthma. However, allergic reactions to orally ingested pectin have not been
      reported. OBJECTIVES: To describe a child with pectin-induced food anaphylaxis
      and to discuss its possible relationship to cashew allergy. METHODS: A 3 1/2-year
      old boy developed anaphylaxis once after eating cashews and later after eating a
      pectin-containing fruit "smoothie." He also has a history of generalized pruritus
      after eating grapefruit. Skin tests or radioallergosorbent tests (RASTs) were
      performed to pectin and other suspected food allergens. RESULTS: The child had a
      positive skin prick test reaction to pectin and a high RAST reaction to cashew
      and pistachio. He had a low-level positive RAST reaction to grapefruit. Results
      of allergy tests for the other potential food allergens were negative. The pectin
      in the smoothie was confirmed to be of citrus origin. Review of previous case
      reports of pectin-induced occupational asthma revealed several patients with
      allergies to and cross-reactivity with cashew. CONCLUSIONS: Ingestion, not only
      inhalation, of pectin can cause hypersensitivity reactions. Cashew, and possibly
      pistachio, allergy may be associated with pectin allergy, and the possibility of
      pectin allergy should be considered in cashew- or pistachio-allergic patients who
      have unexplained allergic reactions.

PMID- 17201236
TI  - Effect of montelukast on symptoms and exhaled nitric oxide levels in 7- to 14
      year-old children with seasonal allergic rhinitis.
AB  - BACKGROUND: Cysteinyl leukotrienes have been found to exert potent inflammatory
      effects in the upper airways and play a fundamental role in the pathogenesis of
      allergic rhinitis. Previous studies have reported increased levels of exhaled
      nitric oxide (eNO) in patients with allergic rhinitis without asthma symptoms.
      OBJECTIVE: To investigate the role of treatment with montelukast on symptoms, eNO
      levels, and peripheral eosinophil counts of children with seasonal allergic
      rhinitis during pollen season. METHODS: A randomized, double-blind, parallel
      group study performed between April and June 2005 in 57 children aged 7 to 14
      years with seasonal allergic rhinitis was performed. The study comprised a 1-week
      screening period, a 1-week run-in period, and a 2-week treatment period with once
      daily montelukast, 5 mg, or matching placebo. RESULTS: No significant difference
      at baseline was found in symptom scores, eNO levels, and blood eosinophil counts
      between the treatment and placebo groups. After 2 weeks of montelukast treatment,
      improvements from the baseline in the daytime nasal, composite, and daytime eye
      symptoms scores were significantly greater in the montelukast group compared with
      the placebo group (P < .001, P < .001, and P < .01, respectively). A significant
      decrease was also found in eosinophil counts (P < .001) in the montelukast group
      compared with the placebo group after treatment. Montelukast treatment did not
      produce a significant effect on eNO levels compared with placebo (P = .96).
      CONCLUSION: Montelukast treatment provided significant improvement in symptoms
      and peripheral eosinophil counts of school-age children with seasonal allergic
      rhinitis; however, it did not show a significant effect on eNO levels.

PMID- 17201235
TI  - Effectiveness of instillation of triamcinolone acetonide into the middle ear for
      eosinophilic otitis media associated with bronchial asthma.
AB  - BACKGROUND: Eosinophilic otitis media (EOM) is a newly recognized middle ear
      disease found in asthmatic patients. EOM is characterized by a highly viscous
      middle ear effusion that contains many eosinophils and is extremely unresponsive
      to conventional treatments for common otitis media. To our knowledge, no systemic
      study regarding the efficacy of treatments for EOM has been performed. OBJECTIVE:
      To determine the effectiveness of instillation of triamcinolone acetonide, which
      is a suspension of steroids, into the mesotympanum and eustachian tube as a
      treatment for patients with EOM. METHODS: We studied the efficacy of the
      instillation of triamcinolone acetonide in 43 ears of 24 patients with EOM.
      Efficacy was evaluated according to the length of the period without middle ear
      effusion or otorrhea. We also determined the otomicroscopic findings and the
      hearing levels before and after therapy. For controls, 27 ears of 14 patients
      treated by topical administration of betamethasone were similarly evaluated.
      RESULTS: The middle ear effusion or otorrhea was controlled for more than 3 weeks
      after 1 instillation of triamcinolone acetonide in 35 ears, and the efficacy rate
      (81%) was significantly higher than that in the controls (7 ears, 26%). In the
      triamcinolone acetonide group, the average air conduction hearing level at the
      speech frequency range was significantly improved, and deterioration of the bone
      conduction hearing threshold was rarely found during therapy. CONCLUSION: The
      instillation of triamcinolone acetonide into the mesotympanum and eustachian tube
      is an effective treatment for patients with EOM.

PMID- 17201237
TI  - Validation of a single survey that can be used for case identification and
      assessment of asthma control: the Breathmobile Program.
AB  - BACKGROUND: Underdiagnosis of asthma and underrecognition of disease severity in
      lower socioeconomic populations continue to be significant health care concerns
      despite national efforts to better educate health care providers. OBJECTIVE: To
      validate a 1-page survey as a point-in-time tool identifying uncontrolled vs
      controlled asthma and moderate-to-severe disease activity in an urban, lower
      socioeconomic pediatric population. METHODS: A previously validated survey (the
      Breathmobile Case Identification Survey) was evaluated as a point-in-time tool
      for identifying children with poorly controlled disease. Clinical validation was
      achieved in children (n = 1,826) presenting to a school-based asthma program for
      either an initial (n = 666) or a follow-up (n = 1,170) visit. Responses were
      compared with a comprehensive evaluation by a physician specialist as the gold
      standard. Response patterns were used to construct multimodel tiered scoring
      algorithms for baseline and follow-up visits that identify children with
      uncontrolled asthma, and children are likely to have moderate-to-severe disease
      activity at that time. RESULTS: Surveys scored using the developed algorithms
      identified children with uncontrolled asthma (sensitivity: baseline, 77.0%;
      follow-up, 71.6%; specificity: baseline, 72.7%; follow-up, 71.5%) and detected
      moderate-to-severe disease activity (sensitivity: baseline, 69.2%; follow-up,
      77.4%; specificity: baseline, 70.2%; follow-up, 70.3%). CONCLUSIONS: The
      Breathmobile Case Identification Survey can be used in lower-socioeconomic, urban
      populations as a point-in-time tool for identifying children with uncontrolled vs
      controlled asthma and moderate-to-severe disease activity.

PMID- 17201238
TI  - Factors associated with acute health care use in a national adult asthma
      management program.
AB  - BACKGROUND: The use of acute health care resources for asthma is considerable.
      Disease severity is an established risk factor, but ethnicity and health care
      factors are less well studied. OBJECTIVE: To investigate the independent
      associations of ethnicity and health care factors with acute resource use for
      asthma. METHODS: Longitudinal data from a national adult asthma management
      program providing universal access to care were analyzed. Outcome measures were
      unscheduled physician visits with urgent nebulization, emergency department (ED)
      visits, and hospitalizations. RESULTS: In multivariate analyses, markers of
      disease severity were found to be significantly associated with all acute
      resource use. After controlling for disease severity, ethnicity was associated
      with increased risk of all acute resource use; Indian (vs Chinese) ethnicity was
      associated with increased risk of unscheduled physician visits (hazard ratio
      [HR], 1.32; 95% confidence interval [CI], 1.03-1.70), ED visits (HR, 1.61; 95%
      CI, 1.12-2.32), and hospitalizations (HR, 1.49; 95% CI, 1.03-2.16). Malay
      ethnicity was associated with unscheduled physician visits (HR, 1.30; 95% CI,
      1.01-1.68) and ED visits (HR, 1.55; 95% CI, 1.09-2.19). Default of follow-up
      appointments was associated with unscheduled physician visits (HR, 1.47; 95% CI,
      1.08-2.00), ED visits (HR, 2.35; 95% CI, 1.59-3.45), and hospitalizations (HR,
      1.74; 95% CI, 1.09-2.76). Poor inhaler technique was associated with ED visits
      (HR, 1.86; 95% CI, 1.05-3.30) and smoking with unscheduled physician visits (HR,
      1.38; 95% CI, 1.09-1.76). CONCLUSIONS: In addition to markers of asthma severity,
      ethnicity, smoking, discontinuity of care, and self-care behavior are risk
      factors for acute resource utilization and represent target groups and elements
      of asthma intervention for improving asthma outcomes.

PMID- 17201239
TI  - Expression of vascular endothelial growth factor and hypoxia-inducible factor in
      the airway of asthmatic patients.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent proangiogenic
      cytokine, and it also increases vascular permeability. It is well known that VEGF
      levels are increased in the airway of asthmatic patients. Hypoxia-inducible
      factor (HIF) induces a rapid and strong increase in VEGF expression. OBJECTIVES:
      To evaluate the relationship between VEGF level and clinical characteristics and
      to determine whether VEGF expression is associated with HIF expression in
      asthmatic patients. METHODS: Bronchoscopy was performed on 30 asthmatic patients
      and 14 control subjects. The concentration of VEGF in the bronchoalveolar lavage
      fluid (BALF) was examined using enzyme-linked immunosorbent assay. We measured
      VEGF, HIF-1alpha, and HIF-2alpha expression on biopsy specimens by means of
      immunoreactivity. RESULTS: The VEGF level in the BALF was significantly higher in
      asthmatic patients than in controls. The VEGF level correlated with eosinophil
      counts in the BALF in asthmatic subjects (r = 0.501; P < .01). However, the VEGF
      level did not correlate with percentage of forced expiratory volume in 1 second
      and airway hyperresponsiveness. Asthmatic patients exhibited higher VEGF, HIF
      1alpha, and HIF-2alpha immunoreactivity in the submucosa than did controls.
      Furthermore, VEGF expression correlated significantly with HIF-1alpha (r = 0.614;
      P = .02) and HIF-2alpha (r = 0.881; P = .001) expression. CONCLUSION: These
      findings suggest that VEGF may play an important role in inflammation and that
      VEGF level is related to HIF in bronchial asthma.

PMID- 17201241
TI  - Elective penicillin skin testing in a pediatric outpatient setting.
AB  - BACKGROUND: Adverse reactions associated with penicillin-type antibiotics are
      common in pediatric practice, leading to the subsequent unnecessary use of
      alternative antibiotics. IgE-mediated penicillin allergy represents only a
      fraction of these adverse reactions. OBJECTIVES: To examine (1) the trend of
      penicillin skin test reactivity during a recent 10-year interval, (2) the
      relative distribution of specific reagents related to a positive skin test
      result, and (3) skin test reactivity as a function of reaction history. METHODS:
      Penicillin testing using 3 reagents--benzylpenicilloyl polylysine, penicillin G,
      and sodium penicilloate (penicillin A)--was conducted in a prospective study of
      359 consecutive patients referred to an outpatient pediatric allergy clinic
      between January 1, 1993, and May 31, 2003. We also retrospectively reviewed
      penicillin skin test results for 562 children previously tested between January
      1, 1979, and December 31, 1992. RESULTS: Between 1993 and 2003, the prevalence of
      penicillin skin test sensitivity markedly declined. Of all the positive skin test
      results between 1979 and 2002, either penicillin G or sodium penicilloate or both
      identified 34%, with sodium penicilloate alone responsible for 8.5%. The rate of
      positive skin test reactions was not significantly different between patients
      with vs without a history of suggestive IgE-mediated reactions. CONCLUSIONS: A
      marked decline in penicillin skin test sensitivity in the pediatric age group is
      identified. The minor determinant reagents penicillin G and sodium penicilloate
      are both necessary for determining potential penicillin allergy. Relating history
      alone to potential penicillin sensitivity is unreliable in predicting the
      presence or absence of a positive skin test result.

PMID- 17201240
TI  - Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL
      13 genes.
AB  - BACKGROUND: Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet
      the pathogenetic mechanisms underlying this disorder remain ill defined.
      OBJECTIVE: To determine if specific single nucleotide polymorphisms (SNPs) of
      interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are
      associated with DA. METHODS: Sixty-two workers with DA confirmed by specific
      inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were
      analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. RESULTS:
      No associations were found with individual SNPs and DA. When stratified according
      to specific diisocyanate exposure, a significant association was found between
      IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate
      (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01)
      only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was
      significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35
      12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype
      combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype
      combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95%
      CI, 1.57-26.12; P = .01). CONCLUSIONS: Gene-environmental interactions may
      contribute to the pathogenesis of DA, and gene-gene interactions may modulate
      this relationship.

PMID- 17201242
TI  - Management of anaphylaxis in child care centers: evaluation 6 and 12 months after
      an intervention program.
AB  - BACKGROUND: Many young children with a history of allergic reactions or
      anaphylaxis spend considerable time in child care centers. We previously reported
      that a significant knowledge deficit exists in anaphylaxis recognition,
      evaluation, and treatment and that greater anaphylaxis education is needed among
      child care providers. OBJECTIVE: To determine whether child care centers can
      recognize, evaluate, and treat anaphylactic episodes in children aged 1 to 6
      years 6 months and 1 year after attending an allergy seminar. METHODS: All 39
      child care centers participating in the original study were selected to complete
      6-month and 1-year follow-up surveys using a similar questionnaire. Those who did
      not attend the seminar or complete all the previous surveys were excluded.
      RESULTS: At 6 months and 1 year, 37 and 29 centers, respectively, completed
      surveys. There was a significant improvement regarding when to administer
      intramuscular epinephrine compared with before the allergy seminar. However, only
      48% of the centers at 6 months (P = .02) and 31% at 1 year (P = .002) knew how to
      correctly administer intramuscular epinephrine compared with 77% four weeks after
      the seminar. With time, there was a significant decline in correctly recognizing
      typical anaphylaxis symptoms, including abdominal cramping, chest tightness,
      shortness of breath, low blood pressure, and diarrhea, whereas symptoms such as
      hives, swelling, and wheezing continued to be identified correctly. CONCLUSIONS:
      There is a need for renewed anaphylaxis education among child care providers.
      Initially, this intervention significantly increased the ability of child care
      center staff to recognize, evaluate, and treat anaphylaxis, but knowledge
      diminished gradually at 6-month and 1-year follow-up.

PMID- 17201243
TI  - Optimizing allergic disease prevention screening in newborns.

PMID- 17201244
TI  - Contact dermatitis to levobunolol eyedrops superimposed on IgE-mediated
      rhinoconjunctivitis.

PMID- 17201245
TI  - Asthma, cockroaches, and protozoal forms: chance or not chance?

PMID- 17201246
TI  - [Androgen regulates penile erection at the peripheral level].
AB  - Androgen has been claimed for so long as a pivotal hormone in regulating male
      sexual function, acting both at the central and peripheral level. We believe that
      androgen is indeed the main synchronizer of sexual activity regulating libido and
      enzymes as nitric oxide synthase (NOS) and phosphodiesterase type 5 ( PDE5) ,
      which are crucial for the erectile process. The main action of androgen is to
      timely adjust the erectile process as a function manifestation of sexual desire,
      therefore finalizing erection to sex.

PMID- 17201247
TI  - [Expression of Bax and Bcl-2 gene in rat testis tissues induced by testicular
      denervation].
AB  - OBJECTIVE: To detect the changes of the expression of Bax and Bcl-2 gene in the
      denervated testis, and to explore the possible mechanisms underlying the
      apoptosis of germ cells induced by testicular denervation at the genetic
      translation level. METHODS: Eighteen mature SD rats (350-375 g) were equally
      divided into 3 groups: a sham operation group( SO) , a superior spermatic nerve
      group (SSN) and an inferior spermatic nerve group (ISN) , and the latter two
      received bilateral surgical removal of the superior spermatic nerve and the
      inferior spermatic nerve, respectively. The animals were killed I month after the
      operation. ISH SP-method was used to detect the expression of Bax and Bcl-2
      protein. RESULTS: Significant up-regulation of Bax protein was detected in both
      the treatment groups 1 month after surgery( P <0. 05) , and the level of Bcl-2
      protein remained unchanged. CONCLUSION: Bax gene is involved in the apoptosis of
      germ cells induced by testicular denervation.

PMID- 17201250
TI  - [Influence of two different vitrification cryopreservation methods on spindles of
      mouse oocytes].
AB  - OBJECTIVE: To investigate the influence of two different vitrification
      cryopreservation methods on the spindles of mouse M II oocytes. METHODS: Three
      groups were included in the experiment, Group A, Group B and the control ( fresh
      oocytes). Mouse oocytes were vitrified by using cryoloop, with ethylene glycol(
      EG) in Group A and with EG + dimethyl sulphoxide ( DMSO) in Group B as
      cryoprotectants, and then the oocytes were placed directly into liquid nitrogen.
      Three hours after the frozen oocytes were thawed they were fixed, and the
      microtubule and chromosome were stained by indirect immunofluorescent method.
      RESULTS: The survival rates of the oocytes after treated by the two vitrification
      cryopreservation methods had no difference ( 80. 3% vs 87. 5% , P > 0. 05) . The
      rate of the intact spindles in Group A was much lower than that of the control
      and Group B ( 15. 2% vs 78.7% , 15. 2% vs 77. 5% , P < 0. 05). But there was no
      difference between the latter two groups (78. 7% vs 77. 5% , P >0. 05). The
      oocytes with normal chromosome in Group A were much less than in the control and
      Group B (17.4% vs 76. 6% , 17. 4% vs 72. 5% , P <0. 05) , with no difference
      between the latter two groups(76. 6% vs 72. 5% , P >0. 05) ; The oocytes with
      abnormal chromosome were more in Group A than in the control and Group B (82. 6%
      vs 19. 1% , 82. 6% vs 27. 5% , P <0. 05) , with no difference between the latter
      two groups (19.1% vs 27.5% , P >0.05). CONCLUSION: The changed vitrification
      cryopreservation method helps conserve the intact spindle configuration of mouse
      oocytes.

PMID- 17201249
TI  - [Effects of ganoderma lucidum spores on cytochrome C and mitochondrial calcium in
      the testis of NIDDM rats].
AB  - OBJECTIVE: To observe the effects of Ganoderma lucidum spores on Cytochrome C
      (Cyt-C) and mitochondrial calcium in the testis of NIDDM rats. METHODS: Fifty
      male Wistar rats were divided randomly into three groups: model, ganoderma and
      normal control, the first two groups injected with 2% STZ through vena caudalis,
      and the last one with half-and-half sodium citrate/citrate buffer solution. Two
      weeks after normal diet, glucose tolerance tests were performed and the rats with
      abnormal glucose tolerance from the model and ganoderma groups received high-fat
      and high-carbohydrate food, the ganoderma group given Ganoderma lucidum spores
      (250mg/[ kg x d] ) in addition, both for 10 weeks. Glucose tolerance tests were
      repeated 1 day before the end of the experiment and the rats were castrated and
      relevant indexes measured. RESULTS: The NIDDM model was successfully constructed.
      In the model group, the levels of mitochondrial Cyt-C and mitochondrial calcium
      were significantly lower (P <0. 05) while that of the plasma Cyt-C was
      significantly higher than in the ganoderma and the control groups. CONCLUSION:
      Cyt-C and calcium ion are involved in the damage of the testis. Ganoderma lucidum
      spores can protect the testis of NIDDM rats.

PMID- 17201248
TI  - [Correlation between brain-derived neurotrophic factor expression in the nerve
      system and erectile dysfunction in diabetic rats].
AB  - OBJECTIVE: To observe the correlation between brain-derived neurotrophic factor
      (BDNF) expression in the nerve system of diabetes mellitus (DM) rats and diabetic
      erectile dysfunction (ED). METHODS: DM rats were induced by injecting
      streptozotocin and erectile function test was done by injecting apomorphine (APO)
      at 1 month, 2 months, 3 months and 4 months. Then the brain, lumbosacral spinal
      cord, thoracic and lumbar sympathetic trunks, penis and prostate were taken from
      the diabetic and normal rats of the same age. The BDNF positive neurons and nerve
      fibers were shown by immunohistochemistry or fluorescence immunohistochemistry.
      The number and the grey density of BDNF positive cells and fibers were detected
      by image analysis. RESULTS: Compared with the control group, the erection
      frequency of the DM rats decreased at 2 months (P <0. 05) , and significantly at
      3 and 4 months (P > 0.01) , and the BDNF positive neurons and nerve fibers in the
      cerebral cortex, lumbosacral spinal cord, thoracic and lumbar sympathetic trunks,
      penis and prostate of 1-month DM rats were reduced (P <0. 05). As time went on,
      BDNF declined progressively. CONCLUSION: BDNF decreases in the central and
      peripheral nerve system in the early stage of diabetes mellitus, wich is closely
      correlated with diabetic ED.

PMID- 17201252
TI  - [Effect of oxidative damage to human sperm in vitro on mitochondrial tRNa LeuUUR
      gene].
AB  - OBJECTIVE: To study the oxidative damage to human sperm mitochondrial tRNA LeuUUR
      gene by reactive oxygen species (ROS) in vitro. METHODS: Spermatozoa of normal
      physiological function selected from semen samples by Percoll gradient
      centrifugation technique were used as normal sperm models, which were divided
      into two groups of 20 cases each, a damage group and a control group, the former
      treated with hypoxanthine xanthine oxidase system and the latter left untreated,
      both incubated at 37 degrees C in aerobic environment for 60 minutes. Sperm DAN
      was extracted, and digestion by the enzymes fpg and ligation-mediated PCR ( LM
      PCR) was performed to map the damage to mitochondrial tRNA LeuUUR gene. The
      spermatozoa were labeled with specific fluorescent probe of Rhodamine 123 to
      measure mitochondrial membrane potential ( MMP) by flow cytometry and observe
      sperm function. RESULTS: Compared with the control group, after the normal
      spermatozoa were incubated with ROS, MMP of the spermatozoa significantly
      decreased ( 116. 27+/-11.72 vs 64.00+/-4. 88) , P <0.05. Digestion by the enzymes
      fpg and LM-PCR showed damage to mitochondrial tRNA LeuUUR, gene. CONCLUSION:
      Reactive oxygen species may inflict oxidative damage on sperm mitochondrial tRNA
      LeuUUR gene and thus affect sperm function ( as shown by significant decrease in
      MMP), resulting in infertility.

PMID- 17201251
TI  - [Aildenafil citrate: a new potent and highly selective phosphodiesterase type 5
      inhibitor for the treatment of erectile dysfunction].
AB  - OBJECTIVE: To evaluate the efficacy and safety of aildenafil citrate, an oral
      phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction.
      METHODS: Integrated analyses were made of 8-week, randomized, double-blind,
      placebo-controlled phase 2 clinical trials involving 250 men with mild-to-severe
      erectile dysfunction of various etiologies who received aildenafil citrate 30 or
      60 mg (n = 167) or placebo (n = 83). RESULTS: The statistic results of
      International Index of Erectile Function, Patient Sexual Encounter Profile (SEP)
      diaries and Global Assessment Question (GAQ) were significantly higher in the
      aildenafil citrate patients than in the placebo controls. The main drug-related
      adverse events were flushing, headache, dizziness and naupathia, which were mild
      and could be self-relieved. CONCLUSION: The aildenafil citrate therapy
      significantly ameliorated erectile function and was well tolerated by a wide
      range of patients with erectile dysfunction.

PMID- 17201254
TI  - [Experimental study of augmentation phalloplasty using tunica vaginalis grafts in
      bilateral albuginea of penile corpus].
AB  - OBJECTIVE: To study the effect and complications of augmentation phalloplasty by
      implanting autogenous tunica vaginalis grafts into the bilateral albuginea of the
      penile corpus. METHODS: Five mongrel dogs underwent augmentation phalloplasty
      with bilateral autogenous tunica vaginalis grafts. The increase in the volume of
      the corpora cavernosa was achieved by applying autogenous tunica vaginalis grafts
      to longitudinal openings made bilaterally in the albuginea along the whole length
      of the penile cavernous corpora. The perimeter of the penile cavernous corpora
      was measured in the flaccid state and during erection and dynamic infusion
      cavernosometry (DIC) was conducted for each dog before and after the operation.
      Histology of the penis was examined using hematoxylin and eosin stains. RESULTS:
      The average increase in the perimeter of the penile cavernous corpora was 21. 1%
      in the erectile state but unobvious in the flaccid state 3 months after surgery.
      There were no statistically significant differences in cavernosometric parameters
      before and after the operation, and neither were there any other severe
      postoperative complications. The grafts had mild inflammatory reaction and
      fibrosis with apparent reformation of the tunica albuginea over the patch site.
      CONCLUSION: The augmentation phalloplasty technique with bilateral autogenous
      tunica vaginalis grafts was proved to be effective and reliable with few
      complications, particularly conspicuous in increasing the volume of the erectile
      tissues during erection.

PMID- 17201253
TI  - [Big Y chromosome not significantly influences outcomes of in vitro fertilization
      and embryo transfer].
AB  - OBJECTIVE: To evaluate the influence of big Y chromosome on the outcomes of in
      vitro fertilization and embryo transfer. METHODS: Data of 127 cycles of IVF/ICSI
      ET, performed in our Reproductive Medicine Center from March 2001 to June 2003
      were analyzed. The patients were divided into two groups according to the length
      of chromosome: Group A, 56 cycles with big Y chromosome RESULTS: No significant
      difference was observed in the quality of embryos and in the and Group B, 71
      cycles with normal karyotype. rates of fertilization, cleavage, clinical
      pregnancy, implantation, miscarriage, ectopic pregnancy, dead infant delivery,
      malformation, CONCLUSION: Big Y chromosome has no significant influence on the
      baby boy delivery and baby girl delivery between the two groups. development of
      embryos and the outcome of pregnancy.

PMID- 17201255
TI  - [RNA interference inhibits VEGF expression and growth of PC-3 in prostate
      carcinoma].
AB  - OBJECTIVE: To construct a eukaryotic expression vector carrying human VEGF RNAi
      and to study the effect of RNA interference on VEGF expression in prostate
      carcinoma. METHODS: VEGF RNAi was synthesized, inserted into the RNA interference
      eukaryotic expression vector, and confirmed by the result sequencing. The vector
      was transfected into prostate cancer PC-3, the VEGF expression detected by
      Western blot and the cell inhibiting rate determined by MTT. RESULTS: The VEGF
      RNAi eukaryotic expression vector was successfully constructed. Compared with the
      empty vector group and the control group, the amount of VEGF protein expression
      was obviously decreased in the VEGF RNAi group. The inhibiting rates were 23.5% ,
      33. 5% and 40. 8% at 24, 48 and 72 h respectively. CONCLUSION: VEGF RNAi can
      inhibit the protein expression and growth of PC-3, which provides an experimental
      base for the biological therapy of prostate cancer.

PMID- 17201256
TI  - [Relationship between ethanol intake and sexual function in rats].
AB  - OBJECTIVE: To investigate the relationship between the intake of ethanol and
      sexual function of rats. METHODS: Sixty adult male Wistar rats were randomly
      divided into five groups: the control, 10% , 20% , 30% and 40 ethanol groups,
      which received. . 9% sodium chloride, 10% , 20% , 30% and 40% ethanol solutions
      respectively at a dose of 2 ml through gastric tubes once a day. Three months
      later, we observed the effects of ethanol on the sexual function of the rats by
      their sexual behaviors, the number of apomorphine-induced penile erections, and
      the content of testosterone in the serum and nitric oxide synthase ( NOS) in the
      penis. RESULTS: Compared with the control group, the number of apomorphine
      induced penile erections in the 10% and 20% ethanol groups was not inhibited
      significantly (P > 0.05), but the latent period of mounting and intromission in
      the 10% ethanol group was prolonged and the sexual behaviors in the 20% ethanol
      group were inhibited except the latent period of ejaculation. The sexual
      behaviors and the number of apomorphine-induced penile erections of the 30% and
      40% ethanol groups were inhibited significantly (P < 0.05). Testosterone in the
      serum and NOS activity in the penis of the experimental groups were reduced (Pat
      < 0.05). CONCLUSION: An adequate volume of ethanol does not induce sexual
      dysfunction in rats, but long term and excessive intake of ethanol may cause
      penile erectile dysfunction.

PMID- 17201257
TI  - [Treatment and prognosis of scrotal extramammary Paget's disease: a report of 23
      cases].
AB  - OBJECTIVE: To evaluate the clinical manifestation, management and prognostic
      characteristics of scrotal extramammary Pagets disease (EMPD). METHODS: Twenty
      three cases of EMPD were identified and retrospectively reviewed, and the
      clinical findings, surgical treatment, pathologic features and prognostic
      characteristics were evaluated. The patients ranged in age from 49 to 72 years
      (mean 62. 4 years). The diagnoses were delayed by 12 to 132 months (67. 6 on
      average) in 9 cases at Stage A1 , 12 at A2, 1 at B and 1 at D. The rate of
      initial misdiagnosis was 91.3% (21/23). Twenty of the patients underwent
      operations, 2 received radiotherapy and 1 chemotherapy. RESULTS: Twenty-two
      patients of the total number were followed up for 7 to 223 months, averaging at
      119, therapy and 1 chemotherapy. of whom 12 remained cancer free, 1 died of
      tumor, 3 died of intercurrent disease, 4 experienced local recurrence, 1 relapsed
      with inguinal lymph node metastasis and 1 developed inguinal lymph node
      metastasis exclusively. Those with relapses received the second surgery, and 5 of
      them survived without cancer and 1 died of intercurrent disease. CONCLUSION: The
      primary treatment of choice for scrotal EMPD is radical excision. Precise,
      histological examination before and during the operation is of crucial
      importance. The positive excisal margins are one of the key causes of local
      recurrence, and the involvement of dermis by Pagets cells may suggest possible
      metastasis. Scrotal EMPD tends to occur as a slowly growing lesion, mainly in the
      elderly, and has a good prognosis in cases of non-invasion. Otherwise the
      prognosis is poor.

PMID- 17201258
TI  - [Management of the impalpable testis in children].
AB  - OBJECTIVE: To explore the management of the impalpable testis in children.
      METHODS: From April 2003 to August 2005, 36 children aged 20 months to 8 years
      with impalpable testes underwent inguinal and laparoscopy explorations. The
      clinical data were reviewed, including the indications of laparoscopy and
      inguinal explorations and the correspondence between the ultrasonic and surgical
      RESULTS: Of the 36 cases (36 / 361 ) of impalpable testis (41 testes),
      laparoscopy and inguinal explorations revealed 18 results. testes to be vanishing
      ones, 21 located intra-abdominally and 2 scrotal nubbins. Manifestations were
      divided into 4 types according to the laparoscopic findings, and 9 testes fell
      into Type I, 9 Type II, 13 Type III and 10 Type IV. Orchidopexies were performed
      by traditional and laparoscopic techniques. The positive diagnoses by ultrasound
      accounted for 75% (27/36). The volumes of the contralateral testes of the
      cryptorchid children were larger than those with intra-abdominal testes and
      testicular nubbins. One case of testicular atrophy was detected by ultrasound in
      the follow-up period. CONCLUSION: Laparoscopy should be performed as a routine in
      children with impalpable testes. Children with Type II testes need not undergo
      inguinal exploration. Inguinal and scrotal explorations are necessary for
      children with Type I testes. Preoperative ultrasonic examination of the
      contralateral testis helps to evaluate vanishing testes or testicular nubbins.

PMID- 17201259
TI  - [Penile squamous carcinoma in circumcised patients: a report 17 cases].
AB  - OBJECTIVE: To discuss the diagnosis and treatment of penile carcinoma in
      circumcised men. METHODS: We reviewed 17 cases of penile carcinoma detected 1
      month to 16 years after circumcision performed in our hospital from January, 1997
      to December, 2004. RESULTS: Of the total number, 11 cases were diagnosed as
      penile carcinoma 1 - 12 months and the others 3 - 16 years after the
      circumcision. Sixteen of them were treated by partial penectomy, anti 1 first by
      extensive circumcision and later by partial and total penectomy successively
      after recurrence. Cloquet nodes biopsy showed 16 cases to be pathologically well
      differentiated and I case moderately differentiated penile squamous carcinoma.
      One died of extensive metastasis, but the other 16 remained disease-free
      survivals. CONCLUSION: Circumcised adult men, especially those over 40 years of
      age, are likely to develop penile carcinoma. Patients with inflammation, plaque
      or ulcer in the prepuce should be checked by pathological biopsy and followed up
      closely. For Stage-I penile squamous carcinoma, partial penectomy is shown to be
      an effective therapeutic option, and Cloquet's nodes biopsy is necessary for all
      patients.

PMID- 17201260
TI  - [A survey of sexual psychology and attitude of Chinese peace-keepers in Liberia].
AB  - OBJECTIVE: To investigate the sexual psychology and sexual attitude of the
      Chinese peace-keepers in Liberia, attempting a correct guidance and psychological
      intervention in this aspect. METHODS: In the middle of the mission tour, a survey
      was conducted among 314 Chinese male peace-keeping soldiers with a self-designed
      questionnaire. RESULTS: More than 90% of the soldiers learned some sexual
      knowledge by themselves; quite a proportion of them were relatively deficient in
      sexual knowledge and lacked sexual education; 77% of them were afraid of AIDS
      even after sexual education. Married soldiers showed more maturity in sexual
      psychology than CONCLUSION: Appropriate psychological intervention the
      unmarried(P <0.05) , but with no differences in sexual attitude( P >0. 05). and
      guidance directed at the particulate population of peace-keepers may help them
      adopt a rational attitude towards their sexual drive and desire and convert,
      their sexual energy into further impetus to better creative performance in the
      peace-keeping mission.

PMID- 17201261
TI  - [Progress in studies of glutathione S-transferase P1 and prostate cancer].
AB  - Prostate cancer ( PCa) is an important genitourinary malignancy with increasing
      morbidity and mortality. Glutathione S-transferase P1 ( GSTP1) , as a phrase- II
      enzyme, has an important role in the activation and detoxification of
      carcinogens. There is a close association between GSTP1 gene polymorphisms and
      the risk of Pca. GSTP1 CpG island hypermethylation can reliably distinguish Pca
      from benign prostatic hyperplasia( BPH) and promises to be an important molecular
      marker for the diagnosis of Pca. This paper summarizes the association of GSTP1
      with the diagnosis and risk of Pca.

PMID- 17201262
TI  - [Ion channels and asthenospermia].
AB  - Asthenospermia is one of the familiar causes of male infertility. Recently, more
      and more studies have discovered that some diseases result from gene defect and
      functional variation of ion channels, known as ion channelopathies. Meanwhile, it
      has been found that even though many diseases do not fall into the category of
      the ion channelopathies, some links or passages during the disease development
      are closely related with the malfunction of ion channels, and many drugs can
      prevent and cure these diseases by acting on ion channels. The relationship of
      sperm physiology and pathophysiology with ion channels is gradually becoming one
      of the hot topics in the current researches. Recent progress in the researches on
      the relationship between sperm motility and ion channels ( including cation
      channel s and anion channels) is briefly reviewed in this article.

PMID- 17201263
TI  - [Biological function of CoQ10 and its effect on the quality of spermatozoa].
AB  - Oxidative damage is one of the important factors inducing the regression of sperm
      quality. CoQ10 is a liposoluble antioxidant that exists in mitochondria and its
      levels in semen and spermatozoa have an important role in the oxidation
      resistance of the male genital system. Exogenous administration of CoQ10 can
      improve the sperm quality and reproductive ability of infertile patients as well
      as exert the effects of an adjunctive therapy on male infertility. This review
      describes the biological function of CoQ10 and its effect on the quality of
      spermatozoa and its effect as an adjunctive therapy on male infertility.

PMID- 17201264
TI  - [Experimental study on the effects of jujingwan on oligospermia].
AB  - OBJECTIVE: To investigate the effects of Jujingwan on the spermatozoal
      ultrastructure and apoptosis of germ cells in oligospermia patients. METHODS: We
      treated 50 oligospermia patients with Jujingwan and observed the spermatozoal
      ultrastructure, the apoptosis of germ cells and the changes in the DNA ploidy
      proportion of spermatogenic cells by electron microscopy and FCM before the
      treatment and 3, 6, 9 and 12 months after it. RESULTS: Jujingwan increased sperm
      acrosome base density 6 months after the treatment and remarkably improved the
      integrity of acrosome membrane 12 months after it, with no obvious pathological
      changes in the nuclei and tails. Three months after the treatment, cell debris
      and apoptotic cells decreased significantly as compared with pre-treatment (P <
      0. 05) , and very significantly 12 months after the treatment (P <0. 01). The
      proportion of haploid spermatozoa increased very significantly (P <0.01) , and
      the lost primary spermatocytes decreased significantly (P <0. 05) compared with
      pre-treatment. CONCLUSION: Jujingwan can increase the density of sperm acrosome
      base and improve the pathological changes of acrosome membrane in oligospermia
      patients; it can improve the activity of acrosome enzyme and the integrity of
      acrosome membrane, decrease the apoptosis rate of germ cells and sperm and
      increase the percentage of haploid spermatozoa; it can also reduce the percentage
      of apoptotic bodies and diploid sperm cells. It is indicated that Jujingwan can
      inhibit the apoptosis of germ cells and sperm and improve spermatogenesis in
      oligospermia patients.

PMID- 17201265
TI  - [Xuanju compound capsule combined with erogenous focus exercise is effective for
      premature ejaculation].
AB  - OBJECTIVE: To investigate the effect of the Chinese medicine Xuanju compound
      capsule combined with erogenous focus exercise on premature ejaculation. METHODS:
      Fifty-two patients with premature ejaculation were divided into a treatment group
      (n = 28) and a control group ( n = 24) , both treated by erogenous focus exercise
      and the former given Xuanju compound capsule in addition. After four weeks of
      treatment, comparisons were made of the sexual satisfaction between the two
      groups. RESULTS: The cure rate and the rate of improvement of sexual satisfaction
      were 21.43% and 67. 86% respectively in the treatment group, significantly higher
      than in the control group. CONCLUSION: Xuanju compound capsule combined with
      erogenous focus exercise is highly effective in the treatment of premature
      ejaculation, with few adverse effects.

PMID- 17201267
TI  - [Cell therapy in the light of evidence-based medicine].
AB  - The results of clinical studies dedicated to treatment with stem cells and other
      cell technologies were analyzed from the position of evidence-based medicine.
      Literature data on the safety of cell therapy and the effectiveness of new
      treatment technologies were summarized according to systems and organs. Cell
      therapy is becoming more and more applicable to clinical practice in patients
      with all groups ofpathology. Its safety and effectiveness has been proved in
      principle, although there are no affirmed algorithms. The authors formulate the
      main principles of further clinical investigations and substantiate the necessity
      to conduct research according to blind randomized protocols, which allow meta
      analysis.

PMID- 17201266
TI  - [Tadalafil and patients preference in the treatment of erectile dysfunction].
AB  - ED treatment has changed fundamentally since phosphodiesterase type 5 inhibitor
      (PDE5-I) came into clinical use. There are three kinds of PDE5-I available at
      present, Sildenafil, Vardenafil and Tadalafil. Tadalafil distinguishes from the
      other two by its uniquely long half-life, which lasts 17.5h, which a
      pharmacodynamic duration of 36h and not influenced by food and alcohol. Thus it
      may enable ED patients to accomplish a spontaneous intercourse without the need
      of prior preparation without, which can boost their confidence and self-esteem
      and, the most important, improve the relationship with their partner. To know
      patient preference counts quite a lot in optimizing the medication ED treatment.

PMID- 17201268
TI  - [The clinicomethodological aspects of the etiology of coronary artery disease].
AB  - Having analyzed more than 150 original papers dedicated to the study of cardial
      pathology risk factors from clinical (specific) and methodological (philosophic)
      points of view, the authors put forward a hypothesis of the etiology of diseases
      (by the example of coronary artery disease) as a "critical mass" of these risk
      factors. Reasoning from it, the authors suggest the ways of using this statement
      by large quantitative evaluation of clinical data, and application of mathematic
      modeling to the diagnostics and prognostics of cardial pathology in each
      particular case.

PMID- 17201269
TI  - [Clinical significance of echocardiographic techniques of right heart
      examination].
AB  - Study of the role and function of the right heart and the peculiarities of their
      remodeling in a range of diseases (heart valvular diseases, pulmonary
      thromboembolism and its complications, cardiomyopathy, combined cardiorespiratory
      pathology, heart failure, essential hypertension etc.) is of great scientific and
      practical interest. An optimal right ventricular (RV) examination should be
      precise, reflect its function objectively, be feasible in everyday clinical
      practice, and provide accurate prognosis. The last decade has been marked by
      search for possibilities to evaluate the systolic and diastolic R Vfunction,
      especially after clinical introduction of Doppler EchoCG. However, publications
      dedicated to the protocol of EchoCG study of the RV, the normal values of its
      structure and function, and their clinical interpretation are still rare. The
      authors of the present work analyze studies on the investigation of the R V and
      offer a protocol with a method of calculation of EchoCG parameters and their
      reference values concerning the right heart.

PMID- 17201270
TI  - [Present-day problems of venous thromboses].
AB  - Venous thrombosis (VT) is a frequent pathology associated with a high mortality.
      A high risk of VT is associated with a variety of diseases, syndromes, and
      situations, connected with a congenital predisposition (thrombophilia) or not.
      Clinical and instrumental data in VT are non-specific. The diagnosis of these
      conditions is very difficult. Correct and timely treatment decreases mortality
      associated with pulmonary arterial thromboembolism (PATE). Unfortunately, this
      index is still very high: a lot of patients die within first minutes and even
      seconds of the moment of pulmonary arterial obturation with a thrombus. All this
      suggests that PATE belongs to diseases that are easier to prevent than to treat.
      In connection with this, a doctor examining a patient must always keep the
      possibility of VT and PATE in mind and evaluate the risk of their development,
      thus taking a decision concerning the necessity, duration, and a method of
      preventive treatment.

PMID- 17201271
TI  - [The main reasons for late diagnosis and errors in the early period of treatment
      of intrahospital myocardial infarction in a general hospital].
AB  - The purpose of the study was to investigate the reasons for late diagnosis and
      late transfer of hospitalized patients with myocardial infarction (MI) to a
      specialized cardiological department. The study shows that the main reasons are
      an atypical clinical picture of MI and a low "infarct alert" of doctors of
      different specialties. The authors analyzed the fullness of urgent medical aid
      and the beginning of treatment in cases of intrahospital MI in patients being
      treated in different hospital departments. The analysis revealed the main
      objective and subjective factors that cause a low frequency of administration of
      thrombolytics, anticoagulants, and disaggregants.

PMID- 17201272
TI  - [Treatment of patients with essential hypertension using bifunctional 24-hour
      blood pressure and ECG monitoring].
AB  - The results of 24-hour blood pressure monitoring (BPM) help to divide patients
      into therapeutic groups according to the leading hemodynamic mechanism offorming
      essential arterial hypertension (EAH). In patients with a mean day heart rate of
      > or =73 bpm antihypertensive therapy should begin with beta1-adrenoblockers when
      not contraindicated. In patients with a mean day heart rate of < or =73 bpm
      antihypertensive therapy may be started with preparations of other pharmaceutical
      groups. In this study, Plendil or Concor was administered as a chronotherapy;
      later their combination was used, and diuretics or ACE inhibitors were added when
      necessary. At any stage of the study, starting from the second week of therapy,
      if blood pressure (BP) was normal and there were ischemic episodes according to
      matched 24-hour BPM and ECG, Cardiket and, when not contraindicated, Aspirin,
      were added. The offered algorithm of choice of therapy made it possible to
      achieve a good antihypertensive effect in 84% of patients and a satisfactory
      effect in 7% of patients, which was accompanied by a tendency towards the
      shortening of total ischemia duration and lowering the frequency of myocardial
      hypokinesia. The effect of the therapy was poor only in 9% of patients, 2% of
      whom one left the study due to adverse reactions before BP was normalized. BP was
      normalized on the 8th week of treatment in 75% of patients. It is appropriate to
      include matched 24-hour BPM and ECG in the follow-up of patients with EAH and
      coronary artery disease upon discharge under the conditions of routine physical
      load. According to 24-hour BPM, mean day heart rate and total length of ischemia
      grow during this period due to an increase in physical and emotional load, which
      requires correction of the therapy.

PMID- 17201273
TI  - [Peculiarities of inflammatory intoxication syndrome in elderly patients with
      extrahospital pneumonia].
AB  - The aim of the study was to evaluate the clinical and diagnostical features of
      extrahospital pneumonia (EHP) in elderly patients to optimize their complex
      medical providence under the conditions of a pulmonological department. In
      particular, the authors studied the manifestations of endogenous inflammatory
      intoxication syndrome (EIIS). The subjects, 142 elderly patients (more than 60
      years of age) with EHP, and the controls, 125 patients under 40, were treated in
      the Pulmonology Department, Burdenko Military Hospital, in 2002-2004. The results
      of the study show that EIIS does not play the leading part in the clinical
      picture in elderly EHP patients; its manifestations are often not as prominent as
      those in the young and thus they can only serve as an approximate indicator for
      complex clinicoradiological examination, undertaken in order to reveal and
      determine the severity of this dangerous disease.

PMID- 17201274
TI  - [Metabolic and hemodynamic effects of pioglitazone in obese patients with type 2
      diabetes].
AB  - The purpose of the study was to evaluate the effectiveness and safety of
      pioglitazon, a hypoglycemizing preparation belonging to the group of
      thiazolidinediones, in treatment of diabetes mellitus (DM) type 2. Twenty DM type
      2 patients were included in the study. The use of pioglitazon during 12 weeks
      resulted in a significant decrease in glycated hemoglobin, fasting glycemia, and
      postprandial reduction in insulinemia and insulinoresistance index HOMA-IR, as
      well as an improvement of lipid blood spectrum and the lessening of visceral
      obesity. Besides, a positive effect on arterial pressure was noted. The study
      revealed no significant adverse effects; good tolerance to treatment was noted in
      90% of the patients.

PMID- 17201275
TI  - [The significance of cardiovascular risk factors and C-reactive protein to the
      development of atherosclerosis in women with systemic lupus erythematosus].
AB  - Compared with general population, women suffering from systemic lupus
      erythematosus (SLE) have signs of coronary artery disease (CAD) five to eight
      times more often, especially in young age. Early development of atherosclerosis
      in patients with SLE is caused by conventional cardiovascular risk factors and
      specific ones, associated with the disease and its therapy. A slight increase in
      such an inflammatory marker as C-reactive protein (CRP) is thought to reflect the
      presence of subclinical inflammation in the vascular wall, connected with
      atherosclerotic process. The authors analyzed the frequency of clinical and
      subclinical (an increase in the thickness of intima-media complex (IMC))
      atherosclerotic manifestations, the summary coronary risk, the prevalence of
      conventional risk factors, and CRP level in 133 female patients with SLE and in
      50 healthy donors. Compared to the control group, SLE patients were younger,
      developed cardiovascular diseases (CAD, stenocardia, myocardial infarction, and
      cerebral stroke (p = 0.05) as well as arterial hypertension more often, had
      higher levels of hs-CRP and triglycerides, and lower levels of high density
      lipoprotein cholesterol (HDLC). There was a positive correlation between hs-CRP
      level and the activity of the disease according to ECLAM score, ES value, IgG and
      IgM levels, hematological disturbances (anemia, leucopenia, and/or
      thrombocytopenia) , and a negative correlation with total cholesterol level, HDLC
      there was a moderate correlation between hs-CRP and a maximal IMC value.

PMID- 17201276
TI  - [The effects of trimetazidine on left ventricular function and physical exercise
      tolerance in patients with ischemic cardiomyopathy].
AB  - Trimetazidine is a new metabolic antiischemic agent, which increases the
      tolerance of cardiomyocytes to ischemia. The aim of the study was to evaluate the
      effect of additional trimatazidine therapy in patients with ischemic
      cardiomyopathy (ICMP) in comparison with standard therapy of cardiac
      insufficiency. According to the results of the study, trimetazidine improves the
      clinical status, functional class of cardiac insufficiency, left ventricular
      ejection fraction, in ICMP patients. Trimetazidine increases physical exercise
      tolerance according to the results of six-minute walking test. Thus, the
      optimization of myocardial energetic metabolism may be a promising perspective in
      the treatment of coronary heart disease with systolic dysfunction.

PMID- 17201277
TI  - [The effects of mexicor on thrombocyte aggregation, blood viscosity,
      hemodynamics, and the clinical course of coronary artery disease].
AB  - The authors analyze their experience in the application of mexicor, a Russian
      cytoprotector, in 50patients with chronic coronary artery disease (CAD) and 51
      patients with acute coronary syndrome. In additional to cytoprotective action,
      the use of mexidor in complex therapy of CAD lowers the functional activity of
      thrombocytes, eliminates high blood viscosity syndrome, and lowers low density
      lipoprotein cholesterol level. These favorable changes in hemorheological
      parameters improves myocardial perfusion, lowers the strength and frequency of
      coronary pain attacks, retards postinfarction left ventricular remodeling, and
      increases the quality of life of patients with various CAD forms.

PMID- 17201279
TI  - [The pharmacoepidemiology of drugs used in treatment of patients with chronic
      obstructive pulmonary disease].
AB  - For one hundred fifty eight patients with chronic obstructive pulmonary disease
      (COPD) were the subjects of a pharmacoepidemiological study. The study found that
      both pharmaceuticals indicated for the treatment of this disease, and drugs of
      low effectiveness, were used in treatment of these patients very intensively.
      Each hospital led its own policy of the distribution of expenses associated with
      COPD treatment.

PMID- 17201278
TI  - [Peculiarities of pharmacotherapy in patients with chronic heart failure].
AB  - A pharmacoepidemiological study of drug consumption was performed on 352 patients
      with III to IV NYHA functional class chronic heart failure (CHF) in different
      hospitals of Kursk region. The study found that only 51% of expenses related to
      pharmacological providence of CHF patients were associated with the drugs used
      directly for the treatment of CHF. Undesirable drug combinations are used more
      often in city hospitals and hospitals belonging to certain organizations than in
      the regional clinical hospital.

PMID- 17201280
TI  - [Definitions of general pathology as predictors of doctor's intervention into the
      natural course of diseases].
AB  - Using modern grouping of general pathological processes, human diseases have been
      divided into three categories according to the initial postulate i.e. the ability
      of the doctor to control the general pathological processes: syndromes and
      diseases underlied by fully reversible general pathological processes; syndromes
      and diseases in which general pathological processes are partially reversible;
      syndromes and diseases which are not controlled by the doctor in principle due to
      the fact that they are underlied by general pathological processes which cannot
      be reversed by a modern doctor.

PMID- 17201282
TI  - [Year of decision].

PMID- 17201281
TI  - [A clinico-morphological analysis of three cases of sudden cardiac death of young
      people].
AB  - Three cases of sudden cardiac death (SCD) of young military men were analyzed.
      Clinicomorphological features and factors associated with SCD in military men
      were studied. The study found that SCD had occurred under the conditions of
      psychoemotional stress, where markers of the stress-related lesion of organs and
      systems responsible for adaptation were present. The last to appear were signs of
      myocardiodystrophy, myocardial hypertrophy, and microfocal cardiosclerosis, as
      well as functional cardiovascular system disorder in the form of pathological
      orthostatic reaction. Sudden death was also associated with anomalous coronary
      arterial development and smoking.

PMID- 17201283
TI  - [Venomous and poisonous animals. II. Viper bites].
AB  - Vipers are the main cause of the snake envenomations on all continents except
      Australia where they are none. Viper envenomation may lead to a minimal
      inflammatory syndrome with clinical (pain, edema) and biological
      (hyperleukocytosis, proteinuria) manifestations that may be accompanied by
      hypotension or shock. Emergency situations are due to hemorrhagic syndrome. In
      frequent cases in which envenomation is limited to a dramatic decrease in
      coagulation factors without clinical manifestations, severe local or systemic
      hemorrhage may occur especially if treatment is delayed. Necrotic complications
      around the bite or in distant vital organs are not uncommon and require careful
      medical and surgical surveillance. Intravenous antivenom therapy is the only
      effective treatment. It should be given as soon as possible but can be effective
      even when administered several days after the bite.

PMID- 17201285
TI  - [Fifth International Medical Science Congress in Madagascar].

PMID- 17201284
TI  - [Phlebotomine sandflies and transmission of disease agents around the
      Mediterranean basin].
AB  - Around 800 species of phlebotomine sandflies are widely distributed in tropical
      and temperate areas. Some sand flies are documented vectors of human disease
      agents including parasitic protozoa, (Leishmania spp), bacteria (Bartonella
      bacilliformis) and viruses (phlebovirus). In addition to presenting morphologic,
      taxonomic and biologic aspects of Phlebotomine sandflies, this report focuses on
      ecologic, epidemiologic, ethologic, and anthropic factors contributing to the
      proliferation of sand flies as exemplified by zoonotic cutaneous and visceral
      leishmaniases around the Mediterranean basin.

PMID- 17201286
TI  - [Implementation of the hypertension network in Mali (RHYTM)].
AB  - In view of the rising prevalence of arterial hypertension and its complications
      throughout sub-Saharan Africa including in rural areas, the Association of the
      Rural Doctors of Mali asked its NGO partner, Sant6 Sud, for assistance in setting
      up a medical network dedicated to hypertension. This report describes the
      implementation of the Mali Hypertension Network (French acronym, RHYTM) that
      involved three stages, i.e., physician training, development of appropriate
      protocols and field trials. The physician training stage was carried out over a
      one-week period and covered all the aspects of hypertension. In the second stage
      international guidelines were used as a basis for development of appropriate
      protocols for the rural setting. Field trials were conducted in the villages to
      verify the feasibility of the protocols and functionality of the network.
      Treatment of hypertension depends mainly on lifestyle and dietetic measures with
      emphasis on reducing salt intake. Drug treatment is based primarily on first
      intention use of thiazidic diuretics. Management of this chronic pathology runs
      up against socio-cultural, economic and logistic obstacles. These problems are
      discussed and possible solutions are proposed. This preliminary experience will
      provide epidemiologic and clinical data on a sample population including more
      than 80000 people and explore the possibility of extending the network to other
      zones in this area of Africa.

PMID- 17201287
TI  - [Sanitary inspection of poultry].
AB  - The purpose of this technical notice is to provide public health agents with
      guidelines for sanitary inspection of poultry. Focusing on zoonosis-related
      hazards, this step-by-step notice presents the symptoms and lesions that must be
      checked for to approve or to reject poultry for human consumption.

PMID- 17201288
TI  - [Vectorial transmission of malaria in shrubby Savannah area at Ganse, Ivory
      Coast].
AB  - A longitudinal entomologic study was carried out in the village of Ganse located
      in the Northeastern Ivory Coast from July 2000 to July 2001. The threefold
      purpose of the study was to index Plasmodium-carrying Anopheles species by
      capturing mosquitoes on human volunteers, collecting larvae in different dwelling
      types, and evaluating the involvement each species in the malaria transmission. A
      total of 4 species belonging to the Anopheles genus were collected in the
      village. Identification of circumsporozoite protein using the ELISA technique
      demonstrated that three species were plasmodium vectors. These species belonged
      to the An. gambiae complex (An. gambiae s.s. 100%), to the An. funestus group
      (An. funestus s.s. 95.6%) and to the An. nill group (An. nili s.s. 100%). The
      estimated mean sporozoite index was 5.9% for An. gambiae s.l., 4.3% for the An.
      funestus group and 2.6% for the An. nili group. The main larva breeding sites
      were standing water such as puddles for An. gambiae s.l., streams with tall
      plants for the An. funestus group and the Comoe River for An. nili group. Because
      peak breeding of these three species occurs at three successive times; i.e., in
      May, September and July respectively, transmission of P. falciparum is continuous
      throughout the year. The transmission rate is high since we recorded up to up to
      410 infected bites per person per year. In addition to showing the presence of
      An. rivulorum-like, our findings in the area demonstrates the important role of
      An. nili s.s. in the transmission and the complexity of the vectorial system.

PMID- 17201289
TI  - [Childhood cutaneous leishmaniasis in Tunisia: retrospective study of 60 cases].
AB  - Cutaneous leishmaniasis (CL) is a widespread parasitic disease that represents a
      major public health problem in several countries including Tunisia. The aim of
      this study was to determine the characteristics of childhood CL in a university
      hospital center in Tunis. The files of all children treated for of CL in the
      Dermatology Department of Habib Thameur Hospital over a 23-year period were
      reviewed. A total of 60 children were included. The mean age was 9.2 years and
      the sex ratio was 0.93. All patients lived or had stayed in an endemic area.
      Infectious risk was highest in autumn (41.6%). The most frequent clinical finding
      consisted of crusty nodules (53.3%) that were most often the only manifestation
      (63.3%) and usually located on the face (65%). Clinical diagnosis was confirmed
      by either peripheral blood smear (56.6%) or histological examination (35%). The
      treatment of choice was Glucantime administered by the intralesional route in 70%
      of patients or by intramuscular route in 30%. The outcome was favorable in all
      cases within 2 weeks to 6 months. Sequels were noted in 9 cases (18%) in the form
      of pigmented (7 cases) or atrophic (2 cases) residual scars. The frequency of
      childhood CL is relatively high especially during the second decade of life.
      Childhood CL is characterized by a generally favorable outcome and lack of
      distinguishing clinical characteristics form adult CL. If possible, therapeutic
      abstention is more widely in the children due to the high risk of adverse
      reactions.

PMID- 17201290
TI  - [Enteric parasites and AIDS in Haiti: utility of detection and treatment of
      intestinal parasites in family members].
AB  - Intestinal parasites and human immunodeficiency virus (HIV) are major health
      problems in Haiti. Both entities are known to interact strongly with cell
      mediated immunity. The purpose of this study undertaken in Port-au-Prince, Haiti
      was to evaluate the risk of enteric parasite transmission between HIV-infected
      patients and family members. Routine examination of stool specimens for parasites
      was conducted in 90 HIV-infected undergoing treatment for intestinal disorders
      due mainly to Cryptosporidium sp. (62%) and 123 healthy family member volunteers.
      A stool sample preserved in 10% formalin solution was examined to detect protozoa
      (MIF, modified Ziehl-Neelsen stain, Uvibio fluorescence technique, Weber stain)
      and helminth ova (Bailenger technique). In addition to Cryptosporidium sp., 14
      parasitic species were identified: 6 Rhizopoda, 3 Flagellata (including Giardia
      duodenalis), 1 Coccidia (Cyclospora cayetanensis), 3 Nematoda (mainly Ascaris
      lumbricoides) and 1 Cestoda (Hymenolepis nana). This is the first time that 5
      protozoa, i.e., Blastocystis hominis, Entamoeba hartmanni, E. polecki,
      Chilomastix mesnili, and Enteromonas hominis, have been reported in Haiti. As
      expected, enteric parasites were less common in HIV-infected subjects undergoing
      medical treatment (11.1%) than in uninfected family members (41.5%) (p = 0.0000).
      Multiple intestinal parasitism (infection by 2 to 4 parasites) was observed in
      19.5% of family members. The findings of this study indicate that detecting and
      treating intestinal parasites in subjects living in close contact with HIV
      infected patients as well as informing family members of the importance of
      personal hygiene in Haiti are highly recommended measures to preserve the health
      of AIDS patients.

PMID- 17201291
TI  - [Detection of anti-Lassa antibodies in the Western Forest area of the Ivory
      Coast].
AB  - Lassa fever is an African viral hemorrhagic fever (VHF) known to be endemic in a
      number of West African countries including Nigeria, Sierra Leone, Liberia and
      Guinea. Despite having common borders with Liberia and Guinea, Cote d'Ivoire has
      never reported any cases of Lassa fever. In March 2000, as part of a research
      project on VHF--mainly yellow fever, Lassa fever and Ebola fever--in Guinea and
      Cote d'Ivoire, an exploratory survey was conducted to assess knowledge about VHF
      and immunological status against Lassa virus among forest workers in the Duekoue
      and Guiglo regions. One hundred and sixty-three male forest workers were
      interviewed using a questionnaire designed to assess risk factors for VHF
      exposure and personal medical history over the last 12 months. Detection of IgG
      antibodies against Lassa virus was performed by immunofluorescence assay with
      Lassa virus antigens from the Josiah and Las/AV strains. The overall prevalence
      of IgG antibodies was 26% (42/161). Among the Lassa IgG positive subjects, 38.5%
      were loggers including 20% that were positive at a serum dilution of 1/40 and
      46.7% were national park workers or forest rangers including 69% that were
      positive at a dilution of 1/40 and more. Forty-one percent of subjects had heard
      of VHF including 14% who attributed it to animals and 2% who attributed it to
      plants. Contact with rodents was frequent and more than 50% of subjects had
      either eaten or skinned rodents. Although the prevalence of anti-Lassa IgG
      antibodies seemed high in the study population, no conclusion can be about level
      of exposure to Lassa virus.

PMID- 17201292
TI  - [Epidemiology of childhood tuberculosis in Libreville, Gabon from 1997 to 2001].
AB  - The purpose of this retrospective study was to determine the epidemiological
      features of tuberculosis patients under the age of 15 years treated at the
      Tuberculosis Control Center in Libreville, Gabon from 1997 to 2001 as a basis for
      improving management. Study criteria included age, sex, BCG vaccination status,
      social level, type of tuberculosis, HIV status and outcome of treatment.
      Statistical analysis was performed using EPI INFO software. The childhood
      tuberculosis rate was 9% with a sex ratio of 1.02 and the most common age group
      was 0 to 4 years. Three fourths of children were from poor zones and 90% had
      received BCG vaccination. The incidence of tuberculosis did not increase from
      year to year. The location of tuberculosis was pulmonary in 77% of cases (n=433)
      and extrapulmonary in 23% (n=129). No case involving meningitis or miliary
      disease was observed. Sputum bacilloscopy was positive in 21% of cases involving
      pulmonary tuberculosis and HIV serology was positive in 4.4% of children tested.
      The success rate was 54%. Tuberculosis-related mortality was 0.7% but 37% of
      children were lost from follow-up. Efforts to control tuberculoses by screening
      children exposed to bacilliferous conditions and vaccinating newborns must be
      continued. Treatment for tuberculosis must be given free of charge and under
      medical supervision as recommended by the World Health Organization.

PMID- 17201293
TI  - [Prognosis of uterine rupture during labor: a 293-case series compiled at the
      Bouake University Hospital Center (Ivory Coast)].
AB  - The purpose of this retrospective comparative study carried out between January
      1, 1996 and December 31, 2001 was to determine the incidence of uterine rupture
      in the maternity ward of the Bouake University Hospital Center and evaluate
      prognosis for the mother and child in function of transportation distance to the
      Center. Patients were divided into two groups, i.e., patients transported from an
      arbitrarily defined safety zone within a 100-kilometer radius of the city and
      patients from outlying areas beyond the safety zone. The overall incidence of
      uterine rupture was 2.44%, i.e., one of 41 deliveries. Hysterectomy was performed
      more often in women from outlying areas: 83.34 % versus 28.57% (p = 0.0000).
      Mortality secondary to uterine rupture was 411.26% overall with a higher rate in
      patients from outlying areas than patients from the safety zone: 29.91% versus
      8.97% respectively (p = 0.0052). Fetal mortality was 100% for patients from
      outlying areas. The prognosis of uterine rupture is less favorable for both the
      mother and child in patients transported from outlying areas.

PMID- 17201294
TI  - [Extent of visual impairment in a population attending an ophthalmology center in
      Africa. Findings in 828 cases at the Tropical Ophthalmology Institute of Africa
      in Bamako, Mali].
AB  - The purpose of this prospective observational study was to evaluate the extent of
      visual impairment in a socially and professionally active population attending
      the Tropical Ophthalmology Institute of Africa (IOTA). Thanks to high recruitment
      rate at the IOTA, which is the third reference eye centre, a total of 828
      patients ranging from 18 and 50 years of age and consulting for the first time
      were included between February 1 and May 4, 2003. Each patient underwent a
      thorough ocular examination. Data were recorded using a dedicated study form.
      Most patients (40%) consulted for reduced visual acuity. Diagnosis determined
      organic disease in 75.6% of cases (626 patients) and ametropia (including
      presbyopia) in 18.5% (153 patients). In the remaining 6% of cases (49 patients),
      ophthalmic examination was normal. Bilateral blindness was observed in 5.8% of
      cases (48 patients). The main cause of bilateral blindness was cataract (19.2%).
      The third most common cause (14.6%) was ocular manifestations of HIV infection,
      confirming that the epidemiology of blindness is changing and that HIV/AIDS
      should be taken into account. Unilateral blindness accounted for 11.5% of cases
      (95 patients). The main causes of unilateral blindness were trauma (50.5%),
      infection (26%) and degenerative disease (18%). Low vision accounted for 8.5% of
      cases (70 patients). The main cause of low vision was ametropia. This is one of
      the few hospital-based studies on causes of blindness in West Africa. The major
      finding is the high prevalence of blinding ocular complications of HIV infection.
      Another important finding is the high incidence of low vision that is often
      disregarded in West Africa.

PMID- 17201295
TI  - [Type 2 diabetes mellitus in children in black Africa: description of first five
      cases in Togo].
AB  - The purpose of this report is to describe epidemiological, clinical and
      therapeutic features of the first five cases of childhood type 2 diabetes
      mellitus (T2DM) documented in Togo. The five children were admitted to either the
      Barruet Clinic (n=4) or Tokoin de Lome University Hospital Centre (n=1) between
      1999 and 2004. All presented one or more of the following risk factors for T2DM:
      obesity, familial history of T2DM, acanthosis nigricans, polycystic ovary
      syndrome, dyslipidemia, and high blood pressure. Age at diagnosis was 15 years in
      two cases and 13, 11 and 12 years in the other three cases (mean, 13.2 + 1.79
      years). There were three females and two males. All five patients were obese and
      had risk factors for obesity (high fat intake, sedentary lifestyle and lack of
      physical exercise). All had a familial history of T2DM and two had Acanthosis
      nigricans. All five patients were treated initially with insulin that was
      gradually discontinued in favor of exercise and diet in four. These are the first
      reported cases of childhood T2DM in Togo. An education campaign is necessary to
      inform the population on about the risk factors for T2DM.

PMID- 17201296
TI  - [Abdominal pregnancy: description of a case observed in Madagascar].
AB  - We report a case of primary abdominal pregnancy observed at the maternity clinic
      in Befelatanana, Madagascar. A 36-year-old woman, gravida 2, para 2, with no
      medical history presented at 40 weeks and 2 days of amenorrhea for sudden
      disappearance of fetal movements. Prenatal visits had been performed on an
      irregular basis by a private-practice midwife. Fetal death was confirmed by
      ultrasonographic examination and subsequent plain abdominal radiographic imaging
      suggested abdominal pregnancy. Laparotomy confirmed diagnosis of primitive
      abdominal pregnancy. Postoperative recovery was uneventful. Based on this rare
      case, the literature is reviewed and the importance of clinical follow-up and
      ultrasonography in detection and management is stressed.

PMID- 17201297
TI  - [Subcutaneous rupture of hydatid cyst of liver: dealing with a rare observation].
AB  - Hydatid cyst of liver is a parasitosis of endemic proportions in Tunisia. The
      purpose of this report is to describe a case involving subcutaneous rupture of a
      hydatid cyst of liver in a 41-year-old patient. Diagnosis was established by
      ultrasonography and CT-scan. The patient underwent surgical treatment and
      recovered uneventfully. Subcutaneous rupture remains an uncommon complication.
      This is only the second case reported in the literature up to now.

PMID- 17201298
TI  - [Gangrene with pyocyanic infection and osteitis in a patient presenting endemic
      Kaposi's sarcoma: case report from Benin].
AB  - Infectious complications involving chronic skin ulcers have been well document
      but superinfection of ulcerated Kaposi's sarcoma nodules by multiresistant germs
      has rarely been reported. The purpose of this report is to describe a case in a
      57-year-old HIV-negative black African man. Kaposi's sarcoma nodules appeared
      suddenly and spread rapidly on the right leg with pain and fever. Onset was
      associated with a laboratory-documented inflammatory syndrome and two metatarsal
      bone defects. Amputation of the leg was required due to the presence of
      multiresistant germs: Pseudomonas aeruginosa, multiresistant Staphylococus aureus
      and Candida albicans. Occurrence of bone lesions beneath superinfected Kaposi's
      sarcoma nodules poses a challenge for differential diagnosis of the underlying
      cause, i.e. either Kaposi's sarcoma or infectious osteitis. Since etiologic
      diagnosis of bone defects requires facilities that are rarely available in an
      African hospital, surgical treatment is the only alternative if antimicrobial
      therapy fails.

PMID- 17201300
TI  - [Toxoplasmosis in French Guiana. Atypical (neo-)tropical features of a
      cosmopolitan parasitosis].
AB  - Toxoplasmosis, a typical cosmopolitan parasitosis, is a major health problem in
      French Guiana. Three factors account for this situation, i.e., (1) severity of
      toxoplasmosis in patients with HIV infection that is particularly prevalent in
      the area, (2) high risk of congenital transmission as shown by the steadily
      increasing prevalence of seropositivity in function of age in most of the
      Guianese population and (3) recent identification of severe primary toxoplasmosis
      infection in immunocompetent patients. In AIDS patients, the epidemiologic
      aspects of toxoplasmosis are correlated to the special features of the HIV
      positive population in French Guiana and its clinical expression, mainly in the
      form of cerebral toxoplasmosis, does not suggest involvement of a particularly
      virulent strain of Toxoplasma. Similarly congenital toxoplasmosis does not
      present special tropical features other than problems associated with prevention,
      diagnosis and follow-up in poor and/or remote settings. These features are fully
      compatible with the classic domestic cat cycle of Toxoplasma gondii. However
      severe forms of primary infection, particularly in immunocompetent adults, appear
      to be associated with atypical features. These forms appear to be correlated with
      a forest-based cycle involving wild cats, which are still numerous in French
      Guiana, and their prey. Ingestion of undercooked wildcat prey, which is also a
      delicacy for man, can also be a source of contamination as can be consumption of
      untreated river water infected with oocysts excreted by felines. Observation of
      higher toxoplasmosis seroprevalence in wild noncarnivorous mammals that live by
      foraging on the ground in uninhabited forest zones suggests that infection can
      also be due to ingestion of oocysts eliminated into the soil. Since there are no
      domestic cats in the area, it must be assumed that these oocysts are shed by wild
      felines. More convincing proof can be seen in the fact that T. gondi strains
      presenting polymorphism, similarities and atypical genetic features can be found
      both in this animal reservoir, particularly in jaguars, and in patients
      presenting the more severe form of toxoplasmosis. In addition to the purely
      scientific interest of confirming the existence of the forest-based cycle,
      knowledge of this atypical form of toxoplasmosis that is probably not confined to
      French Guiana or to the Amazon region has obvious practical medical implications
      not only for diagnosis but also for therapy and prevention.

PMID- 17201299
TI  - [Epidemics caused by group X meningoccal meningitis in Africa in 2006].

PMID- 17201301
TI  - [Malaria in the central highlands of Madagascar: control strategies].
AB  - The purpose of this article is to present data on malaria in the central highland
      plateaux of Madagascar and strategies to improve the national malaria control
      program. Use of rapid diagnosis strips, early home-based fever management with
      pre-packaged chloroquine treatment kits and proposed new therapeutic combination
      based on artemisinine are discussed for management of patients with high
      suspicion of malaria attack. Preventive measures including alternated targeted
      and full-house indoor spraying for vector control, use of insecticide-impregnated
      bednets, implementation of intermittent preventive treatment in risk groups,
      optimization of the epidemic early detection and warning system using the Lot
      Quality Assurance Sampling method for epidemiological investigation if the alert
      threshold is exceeded, and provision of rapid diagnosis strips are presented.

PMID- 17201302
TI  - [Food safety at schools in the Abidjan area (Ivory Coast)].

PMID- 17201303
TI  - [Hepatic veno-occlusive disease due to dietary toxins in a five-year-old child in
      Senegal].

PMID- 17201304
TI  - [Emerging infectious diseases: which threats?].

PMID- 17201305
TI  - It is illegal and unethical to use nitrous oxide/ oxygen conscious sedation
      without scavenging.

PMID- 17201306
TI  - Prevalence of early childhood caries in 3- to 5-year-old children in Philadelphia
      district, Mpumalanga Province.
AB  - INTRODUCTION: Early Childhood Caries (ECC) can be defined as dental caries in
      preschool children. There is a lack of data on the prevalence of ECC at a global,
      national, regional and district level. Hence the severity and extent of the
      disease is unknown. OBJECTIVES: The purpose of the study was to establish the
      prevalence of ECC among 3- to 5-year-old children from the Philadelphia district
      in Mpumalanga. METHODS: A cross sectional study was conducted on 269 children
      aged between 3 and 5 years. The caries status was determined using the decayed,
      missing and filled teeth (dmft) index as described by WHO 1997. RESULTS The
      percentage caries free individuals were 74.6%, 44.2% and 46.6% and the dmft
      values were 0.93, 2.69 and 2.18 for 3-, 4- and 5-year-olds respectively. The mean
      mt and ft values for 3- and 4-year-olds was zero. Among the 5-year-olds, the mean
      mt and ft values was 0.01 and 0.02 respectively. CONCLUSION: For a rural
      community the prevalence of ECC is high. Virtually all caries in preschool
      children from this community is left untreated. There is a need for a properly
      planned preventive strategy for this community.

PMID- 17201307
TI  - Recent advances in local anaesthesia.
AB  - This paper describes developments in the field of dental local anaesthesia.
      Recently introduced injectable agents, advances in the field of topical
      anaesthesia and new delivery systems are discussed.

PMID- 17201308
TI  - Notes from Neil.

PMID- 17201309
TI  - General practitioner's pathology case 9. Focal epithelial hyperplasia.

PMID- 17201310
TI  - General practitioner's radiology case 46.

PMID- 17201312
TI  - Smoking and dental implants--a review.

PMID- 17201311
TI  - Sedation corner 13.

PMID- 17201314
TI  - [Problems of the classification and organization of minor glands located in the
      walls of the hollow internal organs].
AB  - The paper reviews the problems of the classification and anatomical structure of
      minor glands located in the walls of the organs of digestive, respiratory, and
      urogenital systems. A number of adequate terms for the description of the
      structure of the glands, is proposed. Some new data are presented, together with
      the description of most important regularities in the morphogenesis of various
      minor glands, including: similar pattern and heterochronism in the rate of
      ontogenetic development of minor glands, common manifestations of age involution
      of the minor glands in different organs, taking place at different ages, close
      microtopographical relations with the lymphoid structures in the organ's walls.

PMID- 17201313
TI  - [Significance of neuronal, endothelial and inducible NO-synthase isoforms in the
      cardiac muscle histophysiology].
AB  - This review summarizes the information on the interrelations between
      intracellular localization of NO-synthases (NOS) and their regulatory functions
      within different compartments of a cardiomyocyte in the light of general
      conception of Barouch et al. (2002) on the intracellular "spatial
      compartmentalization" of NOS isoforms. Participation of NO in cardiomyocyte
      function control is based on complex spatial compartmentalization of NOS
      isoforms: neuronal (NOS1), inducible (NOS2) and endothelial (NOS3), which possess
      unequal activities resulting in hundredfold differences in the concentrations of
      gas produced. Regulatory role of constititive Ca-dependent NOS1 and NOS3 is
      associated with production of low NO concentrations, which cause a decline in
      cardiomyocyte contractility and a reduction in heart rate. Conversely, Ca
      independent inducible NOS2 appears only in the damaged myocardium with a
      compromised contractile function. NOS2 produces high unregulated NO
      concentrations, which are connected with the generation of peroxynitrites and NO
      cytotoxic action. NOS3 is associated with the membranes of cardiomyocyte caveoli
      and T-tubules, while NOS1 is localized on the sarcoplasmic reticulum membranes.
      NOS isoform compartmentalization promotes regulation of different circuits in NO
      signaling pathways in myocardium, and this principle is a key for understanding
      of contradictions existing in NO biology in the heart. Changes in NOS subcellular
      compartmentalization lead to the increased NO synthesis, reduction of the
      specificity of its effects, disruption of calcium cycle mechanisms,
      electromechanical uncoupling and myocardial contractility failure. The mechanisms
      of selective effects of different NO-ergic regulatory pathways on the activity of
      five major targets in pacemaker and working cardiomyocytes, are discussed.

PMID- 17201315
TI  - [Primary structural moduli of the dorsal thalamic nuclei and motor cortex in
      man].
AB  - The aim of this work was to study the primary structural modular organization of
      neurons in dorsal thalamic nuclei (ventral anterior, ventral lateral, anterior
      medial, anterior ventral, anterior dorsal, medial, nucleus reticularis) and motor
      cortex (areas 4 and 6) in man using the methods of Nissl, Kluver-Barrera and
      Golgi silver nitrate impregnation. It was shown that in both dorsal thalamic
      nuclei and motor cortex neurons had regular organization--they were forming small
      groups or short chains and meet specific criteria. These neuronal associations,
      formed single structural units, that were called primary structural moduli.
      Comparison of primary structural moduli found in dorsal thalamic nuclei and motor
      cortex has demonstrated the identity of their organizational principle. The
      differences were only in the cells, that formed primary structural moduli. Thus,
      in human dorsal thalamic nuclei and motor cortex two principles of neuronal
      organization into primary structural moduli were detected--group and chain.

PMID- 17201316
TI  - [Spinal cord regeneration in rats after thoracic segmentectomy: growth and
      regeneration of nerve fibers].
AB  - As it was described in a previous paper (Morphology, 2005, v.127, Iss. 2), spinal
      cord (SC) consolidation after thoracic segmentectomy in rats took place via
      connective tissue scar formation in the area of trauma, which was accelerated
      when SC defect was filled with by the collagen gel (Spherogel). In this paper, on
      the basis of semithin section analysis and transmission electron microscopic
      study, it was shown that regenerating nerve fibers crossed the connective tissue
      within the formations, which were structurally identical to peripheral nerves. In
      the zones of rarified SC substance, caudally to the site of trauma, myelination
      of growing axons was realized by glial cells without the formation of the nerve
      truncs. In the white matter, within the fasciculi of SC lumbar segments, multiple
      thin regenerating fibers were seen in the area of degenerated myelinated nerve
      fibers.

PMID- 17201317
TI  - [Morphometric characteristic of epitheliocytes of choroid plexus of human brain
      ventricles in aging].
AB  - Epitheliocytes of choroid plexus vili of lateral (glomus), III and IV (lateral
      portion) brain ventricles were studied in humans aged 22 to 89 years. Height,
      width and profile area of the cells, as well as nuclear and cytoplasmic profile
      areas were measured and nucleo-cytoplasmic indexes were calculated. The shape of
      epitheliocytes was found to be variable and to be associated with their location
      on the vilus surface. Epitheliocyte height, cytoplasmic and cell profile area
      were maximal in the choroid plexus of lateral ventricle, nuclear profile area and
      epitheliocyte nucleo-cytoplasmic index--in the choroid plexus of IV ventricle.
      These differences in epitheliocyte parameters are thought to be associated with
      the peculiarities of their functioning. In the process of aging, the dimensions
      of epitheliocytes and their nuclei were found to decrease, while the nucleo
      cytoplasmic index was reduced, reflecting the development of adaptational
      remodeling.

PMID- 17201318
TI  - [Role of nitric oxide in apoptosis of retinal neurons in human fetuses].
AB  - The localization of NADPH-diaphorase (NADPH-d), inducible NO-synthase (iNOS) and
      TUNEL-immunoreactive neurons was studied in the retina of human fetuses in the I
      III trimesters of pregnancy. High NADPH-d activity was found in internal segments
      of photosensory cells, amacrine and ganglion cells. The population of NADPH-d
      positive amacrine cells included three types of neurons. Neurons of the 1st type
      had large size and scarce dendritic field, occupying the inner nuclear and outer
      plexiform layers. Small neurons of the 2nd type were located in the inner
      plexiform layer. Ectopic amacrine cells of 3rd type could be found in the outer
      part of the ganglion cell layer. High density of the NADPH-d-positive neurons was
      detected in the central portion of retina surrounding fovea centralis and the
      optic disk area. The activity of NADPH-d was found to grow progressively in
      ontogenesis and to correlate with the appearance of immunoreactive iNOS in
      neurons. Immunoreactive iNOS marked a subpopulation of amacrine and ganglion
      cells which appeared in weeks 20-21 of gestation and attained maximal
      immunoreactivity by the end of the III trimester. TUNEL-immunoreactive nuclei of
      the neurons with the signs of the apoptotic destruction were found in weeks 30-31
      of gestation. The highest apoptotic index was found in the population of ganglion
      cells. The data obtained strongly suggest that NO is a factor, mediating the
      neuronal apoptosis during the critical period of a differentiation of
      interneuronal connections in the human retina.

PMID- 17201319
TI  - [Changes in the ultrastructure of histohematic barrier in the rat right atrium
      after short-term and prolonged heat stress].
AB  - In experiments on rats, changes of the ultrastructure of myocardial histo-hematic
      barriers in the right atrium during short-term and prolonged heat stress were
      studied. Short-term heat exposure (40 degrees C, 30 and 60 min) increased the
      rectal temperature by 3.0-3.5 degrees C. Immediately after heat exposure and 24
      and 48 h following the exposure, the destructive and compensatory adaptive
      alterations in the microcirculatory bed were detected, accompanied by an edema of
      the pericapillary space and the changes in the size of mitochondria under the
      cardiomyocyte sarcolemma. Prolonged heating (40 degrees C, 4 h daily for 28 days)
      led to an increase in the rectal temperature by 0.4-1.6 degrees C. Changes in the
      microcirculatory bed had both dystrophic and compensatory adaptive nature.
      Erythrocyte and thrombocyte sludge and erythrocyte lysis were found in the lumen
      of microvessels. The number of endocytotic vesicles in endotheliocytes was
      variable; endotheliocyte nuclei had increased electron density and irregular
      outline. Myelin-like structures and apoptotic bodies were found in the
      pericapillary spaces. Under the cardiomyocyte sarcolemma the accumulation of
      mitochondria and sarcoplasmic vacuolization were noted. Comparison of short- and
      long-term effects of heat on histohematic barriers in the right atrium shows more
      significant changes after prolonged heat stress.

PMID- 17201320
TI  - [Ultrastructure of macrophages detected after implantation of the Alloplant
      allogenic biomaterial].
AB  - The ultrastructure of macrophages detected in rats after subcutaneous
      implantation of the dispersed allogenic Alloplant biomaterial was studied. It was
      found that with the Alloplant biomaterial implantation the conditions were
      created promoting the concentration and complete maturation of different
      macrophage subpopulations. Their functional activity and interaction with other
      cellular populations result in complete regeneration of the connective tissue.
      The data obtained confirm the concept of main regulatory role of macrophages in
      the intercellular interactions during tissue repair and support the hypothesis of
      bicomponent mechanism of collagen fiber formation in the place of the Alloplant
      biomaterial implantation.

PMID- 17201321
TI  - [The characteristic of proliferative activity of thymocytes and peripheral blood
      lymphocytes in the offspring of females with experimental chronic liver diseases
      of various aetiology].
AB  - The aim of the study was a comparative analysis of the proliferative activity of
      thymocytes and peripheral blood lymphocytes in the offspring of female rats with
      chronic liver pathology of various genesis. In adult female Wistar rats toxic and
      autoimmune forms of liver lesions were modeled. The offspring of these
      experimental animals was studied at different time points of postnatal
      ontogenesis. Proliferative activity of thymocytes and lymphocytes was estimated
      by counting the proportion of cells with multiple nucleolar organizing regions
      (AgNORs) and using the cytofluorometric method with acridine orange. In the
      offspring of experimental animals, the depression of proliferative activity of
      thymocytes as well as the increase of the proliferative activity of peripheral
      blood lymphocytes were found at all the time points studied. This was indicated
      by a change in a relative number of AgNORs-activated cells and a decrease of
      nucleic acid content in cortical thymocytes.

PMID- 17201322
TI  - [Histophysiology of lymphocyte-tissue complexes in human fetal intestine].
AB  - Using histochemical and immunological methods, the development of lymphocyte
      tissue complexes in the distal part of human fetal intestine (appendix, Peyer's
      patch) was studied in relation to the changes taking place in the ileocecal lymph
      nodes. It was found that this autonomous gut immune system started to function in
      the second trimester of fetal development. It is dominated by T-cell system of
      the immunity. After the appearance of meconium in the intestinal lumen, the
      phenotypical diversity of lymphocytes within the organ was increased, but it did
      not reach the level found in mature organism. The ileocecal lymph nodes are
      distinguished by their lymphocyte composition as a T-cell depot in this
      interorgan and intertissue system, which provides essential homeostasis of the
      developing fetus.

PMID- 17201323
TI  - [Changes in the pancreas structure after exposure of the body to gravitational
      overloads].
AB  - The aim of this study was to determine the changes in the pancreas structure
      after acute and chronic exposure of organism to gravitational overloads (GO). The
      experiments were conducted in 36 outbred albino male rats, 12 rats formed the
      control group. GO effect was modeled using the centrifuge; the value of the
      overload thus created amounted to 4,0-6,0 gravitational units. Pancreas structure
      was studied using histological, electron microscopic and morphometric methods. It
      was found that after acute exposure to GO, mainly the reactive changes were
      demonstrated all the pancreatic structures studied: acinocytes, endocrinocytes,
      blood vessels and nervous apparatus. Chronic exposure to GO resulted in both
      reactive modifications, similar to those described after an acute exposure, and
      various compensatory-adaptive and destructive changes.

PMID- 17201324
TI  - [Structure-functional changes in the rat pancreas after glucose injection].
AB  - Electron microscopic method was used to study the effect of hyperglycemia on the
      pancreas of albino rats (n = 20) after intraperitoneal administration of 40%
      glucose solution (daily, for 5 days). The data obtained suggest that repeated
      administration of glucose was accompanied by marked changes in the structure B
      endocrinocytes, indicative of the increased secretion of the insulin. This
      resulted in the appearance of new small pancreatic islets, that consisted of B
      endocrinocytes and acino-insular cells. Most frequently acinar-insular cells were
      located at the periphery of newly formed islets. The latter often had a symplast
      type structural organization.

PMID- 17201325
TI  - [Dynamics of proliferation and apoptosis in the human bulbourethral glands in the
      process of aging].
AB  - The dynamics of the processes of proliferation and apoptosis in the epithelium of
      the bulbourethral glands in men aged 17-90 years was studied using monoclonal
      antibodies against PCNA and p53. Higher levels of cell reproduction and cell
      death were noted in the glandular duct epithelium as compared to those in
      secretory portions. Age-related increase in apoptosis which correlated with the
      activation of the glandular cell proliferation was shown. In old men, apoptosis
      in the bulbourethral glands was accompanied by the tendency to reduced cell
      proliferation. The correlation between the processes of cell reproduction and
      cell death in the epithelium of the bulbourethral glands, as well as their
      dependence on blood androgen levels, are discussed.

PMID- 17201326
TI  - [Morpho-functional parameters of the corpus luteum in healthy women and in
      patients of reproductive age with uterine myoma].
AB  - Ovarian corpus luteum of menstruation at the stage of its peak activity was
      studied in normal women and in patients with proliferative uterine myoma using
      ultrasonography (intravaginal color Doppler imaging), laboratory analyses
      (progesterone and estrogen concentrations in peripheral blood) and morphological
      (histological, histochemical and morphometric) methods. In patients with
      proliferative uterine myoma, the defective corpus luteum was detected, as
      indicated by the prevalence of small granulosa lutein cells, insignificant amount
      and uneven distribution of lipid inclusions in their cytoplasm, marked reduction
      of progesterone concentration in peripheral blood, unechogenicity, low degree of
      vascularization and increase in the value of resistance index of ovarian stromal
      arteries.

PMID- 17201327
TI  - [Cytochemical study of dehydrogenase activity in the tissues of the pig female
      genital system after injection of xenogenic cerebrospinal fluid (a cytochemical
      study)].
AB  - The experimental study was performed to evaluate the biological effects of
      parenteral injection of cerebrospinal fluid (SCF) on the uterus, uterine tubes
      and the ovary of piglets aged 60 days. Lactating cows aged 4-6 years after first
      calving were taken as SCF donors, since their SCF contained maximal spectrum of
      biologically active substances. For injection the whole SCF, SCF after passage
      through bacterial filters and SCF supernatant were used. The effect of SCF was
      assessed using histological and histochemical (succinate- and lactate
      dehydrogenases demonstration) methods. It was found that SCF preparations studied
      had differential effect on oxidative-reduction processes in the tissues of
      reproductive system organs of immature pigs, that is associated with the broad
      spectrum of biologically active substances in mammalian SCF.

PMID- 17201328
TI  - [Use of zinc-containing dehydrating fixatives for neurohistological studies].
AB  - The suitability of zinc-containing dehydrating fixatives for neurohistological
      study of paraffin sections using Nissl staining and immunocytochemical techniques
      was examined. It was found that zinc-containing dehydrating fixatives (zinc
      ethanol-formaldehyde and zinc-acetone-isopropanol-formaldehyde) had a capacity
      for good preservation of both structure and antigenic properties of the nervous
      tissue and could be recommended for application in neurohistological studies.

PMID- 17201329
TI  - [Discussion on the sensory innervation of the brain].
AB  - In reply to the article of an opponent, the author presents new personally
      obtained data on the similarity of some brain neurons possessing asynaptic
      dendrites and innervating the perivascular space, pia mater (from inside), or
      having the direct contact with the ventricular cerebrospinal fluid, to the local
      autonomic Dogiel's II type neurons of the viscera. Author also demonstrates
      personal electron micrographs showing the terminals of asynaptic dendrites of
      brain neurons which are not different in any aspect of their ultrastructure from
      the terminals of visceral receptors. The facts are presented, that, in author's
      opinion, refute the opponent's conceptions on the impossibility of the various
      receptor functions of the cilia in general, and in ciliated neurons, in
      particular, on the development of sensory neurons from the neural crest only, and
      on the impossibility of the sensory innervation of the brain tissues, in
      principle.

PMID- 17201330
TI  - [Evolutionary approach to the understanding of structural and functional
      organization of Golgi apparatus].
AB  - This article analyzes the literature data related to the discussion of the main
      models of intracellular protein transport, including vesicular and cistern
      maturation-progression models. The existence of an important Golgi complex (GC)
      component--continuous tubular structures--is emphasized and their possible
      participation in the intracellular transport is discussed. A brief review is
      presented, describing the peculiarities of intracellular traffic in eukaryotic
      species belonging to different stages along the evolutionary process. The
      evidence suggests that in higher eukaryotes, the dynamic membranous GC system was
      formed on the basis of tubular networks that performs protein sorting and
      selective protein transport.

PMID- 17201331
TI  - [Main directions of the improvement of quality of educational literature in
      histology, cytology and embryology].

PMID- 17201332
TI  - [The degree title arrived. Room for growth].

PMID- 17201333
TI  - [The shaken baby syndrome].
AB  - The shaken baby syndrome is caused by a violent jerk or shaking of a child's or
      infant's head; on some occasions this syndrome is defined as a form of child
      abuse. This relatively unknown syndrome can produce multiple lesions in the
      victim; these lesions are not evident externally in the majority of cases. The
      authors have reviewed numerous articles so that they can define this syndrome's
      basic characteristics which bear much weight in the early detection of this
      syndrome and moreover on adequate prevention of this syndrome by health
      professionals since this syndrome may cause grave and permanent repercussions in
      the child which undergoes it.

PMID- 17201334
TI  - [Aging, nutrition and social care. One "ABS" in Barcelona].
AB  - According to a report by the Spanish Society of Public Health and Sanitary
      Administration in 1998, the general population is undergoing demographic changes
      due to an increase in life span and a decrease in the birth rate. With an
      increase in age, there is a greater risk to suffer a nutritional deficit;
      constantly on the rise, poor nutrition leads to poor health among Europeans. The
      physical and mental health state of the elderly depends to a high degree on
      eating habits during one's entire adult life. On the other hand, as health
      professionals we are interested in knowing the availability of resources the
      elderly can avail themselves to in order to satisfy their needs for affection,
      love, acceptance, sense of belonging, identity and security; which is to say
      their social network. The objective of our study was to know the
      sociodemographical characteristics, the nutritional state and the social network
      for persons above 65 years of age in the "Eixample" District in Barcelona.

PMID- 17201336
TI  - [Nursing report on patients' release. Do observations coincide?].
AB  - The Nursing Report upon a patient's release guarantees treatment continuity. The
      nursing supervisor carries out an annual internal audit of all reports. A second
      investigator reviews this audit. The authors want to show how a degree of
      concordance between these two observations is achieved. The authors analyzed 31
      items in all the reports, a total of 233, filled out by the gynecology service in
      2004. The Kappa index was used to evaluate the degree of concordance. The second
      investigator analyzed 15% of these reports. The kappa index was calculated and
      the authors evaluated the discrepancies of those items with k less than or equal
      to 0.80; concepts were redefined. The second investigator revises 15% of the
      reports and carried out a new analysis of the discrepancies. Finally this second
      researcher supervised the remaining 70% of the reports and carried out a final
      analysis.

PMID- 17201335
TI  - [Work responsibilities. Critical care unit].
AB  - The authors quantify the work load nurses have, analyzing the relationship
      between the level of treatment planned and the operative level by means of a
      prospective study carried out over a three month period at the Anesthesia and
      Reanimation Unit at the Clinical University Hospital in Santiago de Compostela;
      this study had a total of 233 patients. The authors observed that the work load
      for nurses lie above the recommended values and there exists a difference between
      the planned treatment level and the operative treatment level.

PMID- 17201337
TI  - [Primary enuresis in children. Clinical procedure management].
AB  - By means of a management according to strategic processes method, the author
      designs a nursing sub-process "to control primary enuresis in children"; the
      author unfolds the mobilization phases and stages, the stabilization process, the
      management control method and the produce improvement method. In order to carry
      out the working procedures, those involved applied the NANDA-NOC-NIC nursing
      methods which permitted a nursing practice based on the observed evidence.

PMID- 17201338
TI  - [Syphilis in the XVII century, treatment in a hospital in Toledo].
AB  - The author analyzes the work developed by the Nursing staff in a hospital
      specializing in the treatment of buboes. This evaluation is based upon the rules
      which were set by the policies of this center; furthermore, it is supplemented by
      treatment for this disease used during that time period.

PMID- 17201339
TI  - [Osteoporosis. Long-term health risks].
AB  - This article provides an explanation for menopause and the factors which bear an
      influence on its development. The authors analyze the preventive role of dietary
      habits. A later article will analyze the function of physical exercise.

PMID- 17201340
TI  - [Cutting and incision tools: the scalpel: blades].
AB  - The blades of a scalpel form an extensive set of stainless steel cutting sheets
      which have a fenestration where they link to a scalpel's handle comfortably;
      these handles can be small, number 3 or large, number 4.

PMID- 17201341
TI  - [Progress in the treatment of gastrointestinal cancers due to introduction of
      neoadjuvant concept].
AB  - Formerly the treatment of gastrointestinal cancers was exclusively surgical.
      Though the results were improved by increased radicality, the real progress was
      achieved by the introduction of multimodal therapy, particularly by the
      neoadjuvant concept. The basic prerequisite for neoadjuvant treatment is precise
      staging and risk assessment. According to staging patients can be divided into
      three categories: (1) Early cancers, confined to the mucosal and submucosal
      layers, are approached with primary surgery. (2) Systemically metastasized tumors
      receive merely palliative treatment. (3) Locally advanced cancers are treated by
      neoadjuvant therapy. Due to neoadjuvant treatment the tumor can be downsized (or
      downstaged) in some patients. These are the responders benefiting from the
      therapy, because of the increased RO-resection rate, decreased recurrence rate
      and improved survival. The non-responders, by contrast have poor prognosis.
      Neoadjuvant treatment considerably improved the chance for cure for patients with
      gastrointestinal cancers, thus this method became an evidence based treatment for
      locally advanced gastrointestinal cancers.

PMID- 17201342
TI  - [Molecular mechanisms in development of colorectal cancer metastasis].
AB  - The colorectal cancer can be mainly treated by surgery. Metastases are
      responsible for the poor prognosis. Development of metastases is a difficult,
      multi-level regulated process with complex molecular interactions. During the
      past decade, these mechanisms have become better known. Some parts of it had been
      clarified, others are still targets of the research. Analysis of this system can
      lead to find substances or methods, which could inhibit the development of
      metastases. Our aim was an exposition of the factors taking part in the process
      of development of colorectal metastases.

PMID- 17201343
TI  - [Surgical treatment of morbid obesity].
AB  - Morbid obesity is a multicausal disease with great importance because of the life
      threatening associated co-morbidities. Its treatment has many different aspects
      and needs multidisciplinary collaborations. The most powerful way of treatment is
      the surgical intervention which demands thorough preoperative investigations and
      patient selection. The bariatric surgical procedures went through significant
      development and many of them have only historical importance. Different
      interventions can be classified to malabsorptive, restrictive and combined
      subgroups. In Europe the laparoscopic adjustable gastric banding seems to be the
      most widely applied procedure which is purely a restrictive intervention. Apart
      from the low rate of complications it has many advantages which were not
      characteristic of the formerly used procedures. These include: minimal
      invasiveness, reversibility, preservation of the gastrointestinal anatomy,
      adjustability for demands of care.

PMID- 17201344
TI  - [Anterior approach for liver resection in the cases of the treatment of large
      liver tumors].
AB  - The authors compare the results of the patients who underwent right
      hemihepatectomy through anterior approach with those by conventional
      hemihepatectomy. In 119 patients hemihepatectomy was done, 52 of them were
      anterior approaches. We used this technique when the tumor was large, or it
      seemed to be fragile and its mobilisation could be dangerous or infiltrated the
      diaphragm or the the hepatic vein's preparation was difficult or impossible. We
      started the operation with dissecting parenchyma from the anterior surface toward
      hilus without preparation and ligation of the affected vessels and bile duct. No
      patient died following anterior technique. Death and reoperation occurred in two
      cases following conventional hemihepatectomy. The operation time and the average
      nursing days was not significantly different. The blood transfusion was
      significantly less during anterior approach. However, between the two groups, in
      those cases when the operations were performed because of liver malignancies,
      there were no differences regarding to survival rate after 62 months follow up in
      contrast with the literature. The anterior technique used and modified by authors
      can be performed safely. The blood consumption is significantly less in the cases
      of anterior technique. There was no significant difference between the groups
      regarding to the operation-time and the average nursing days. The median survival
      rate was similar in both groups. Our team suggest this method of the anterior
      approach for liver resection in the above mentioned cases.

PMID- 17201345
TI  - [Minimally invasive video-assisted thyroidectomy (MIVAT)].
AB  - Minimally invasive video-assisted thyroidectomy (MIVAT) was published in 1998. In
      this paper authors describe their initial experiences with this new technique,
      which is the first publication in their country on this topic based on authors
      knowledge. Ten patients were selected for MIVAT. Selection criteria were nodule
      size less than 30 mm, thyroid lobe volume less than 20 ml, no thyroiditis, no
      previous neck surgery or irradiation. The procedure was carried out through a 20
      25 mm central incision above the sternal notch. Dissection was performed under
      endoscopic vision, using endoscopic, some special and conventional instruments.
      Authors performed 1 total thyroidectomy, 6 lobectomies, 2 lobectomies with
      subtotal resection on the opposite side, and 1 resection of thyroid isthmus. Mean
      operative time was 77 minutes. No conversion to open procedure was performed. No
      recurrent laryngeal nerve palsy or postoperative hypocalcemia were observed
      postoperatively. The mean hospital stay was 2 days. The cosmetic result and the
      postoperative distress were considered very good by the patients. The authors
      conclude that MIVAT is a safe and feasible procedure. The indications are
      limited, but in this small group of patients offer excellent cosmetic results
      with less postoperative distress.

PMID- 17201346
TI  - [Surgical aspects of breast cancer screening at our hospital].
AB  - In addition to discussing effectiveness of breast cancer screening initiated
      within the National Public Health Programme, the problem of how to treat non
      palpable, early invasive and in situ breast cancer (DCIS) is considered. The
      theoretical issue of the sentinel lymph node and its impact on biopsy practice
      have also been dealt with. In the authors' region, screening was introduced in
      1999 and after a short break has been continued since 2002. Patient data of three
      periods, each of two years, each with ten years' interval (1982-1983, 1992-1993,
      2002-2003) have been analysed. Changes in the number of surgical operations and
      tumour size, incidence of in situ cancer, lymph node involvement and distribution
      of types of surgery have been studied. Biopsy of the sentinel lymph node has been
      applied since May, 2003 (with 45 biopsies performed until 31 December, 2004). The
      number of persons participating in the screening programme has gradually
      increased, the number of surgical operations because of breast cancer increased
      from period to period. Size of the detected tumours has decreased, the percentage
      of non-palpable cases has been significant (445 surgical interventions during the
      years 2002-2004: surgery: 19%). The proportion of DCIS has increased to nearly
      four times as compared to data of years immediately preceding the era of
      screening (1993-1998: 11 cases, 2%; 1999-2004: 62 cases, 7.5%). Specificity of
      sentinel lymph node biopsy was 90%, with a sensitivity of 65%. The proportion of
      breast saving surgery has increased above 50%. The authors regard screening as
      successful, in their opinion, its benefits cannot be questioned, in spite of some
      controversial issues. As to the treatment of non-palpable, early invasive cancer,
      they underline the importance of preoperative evaluation--cytology, core biopsy-
      and establishing dignity. The issues of localisation--wire hook marking--and
      histological processing--large blocks--have also been dealt with. In spite of the
      fact that the risk for potential malignancy of DCIS lesions has not yet been
      fully clarified, adequate treatment is indicated; the authors take stand on the
      issues of indication for surgery, postoperative radiotherapy and use of
      Tamoxifen. Indications and contraindications of sentinel lymph node biopsy have
      been summed up.

PMID- 17201347
TI  - [The effect of mammographic screening on tumor size, axillary node status and the
      degree of histologic anaplasia].
AB  - Breast cancer is the most frequent malignant tumor in women in Hungary.
      Significant reduction of mortality has been brought about not only by the
      increasing efficiency of complex therapy but also by regular mammographic
      screening. Of the histopathological data of 633 patients operated with primary
      breast tumor at the 1st Surgical Clinic of the Debrecen Medical University
      between January 1st 2000 and December 31st 2004, the authors analyzed tumor
      diameter, axillary node status and the degree of histologic anaplasia and
      compared them with the data of mammographic screening. RESULTS: Of the
      "screened"patients, 70.7% were diagnosed with T1 size tumors, 28.5% with T2 size,
      and 0.8% with tumors bigger than that. In the "unscreened" patients, our findings
      were 44.3%, 45.9% and 9.8% respectively. Within T1 tumors, Tla tumors were found
      in 11%, TIb in 37.6% and T1c in 51.4% in the "screened" group of patients, while
      the "unscreened" group's results were 2.3%, 12.6% and 85% respectively. 72.7% of
      the "screened" patients and 56.2% of the "unscreened" patients were found to be
      axillary node-negative. A study of the degree of histologic anaplasia showed G-I
      tumors in 15.6%, G-IIs in 62.1% and G-IIIs in 22.3% of the "screened" patients.
      The corresponding values for the "unscreened" patients were 6.1%, 53.8% and
      40.1%, respectively. The differences were highly significant (p < 0.001) in all
      the parameters investigated. The authors have found a significant increase in the
      proportion of node-negative patients and patients with smaller tumors even after
      the first round of mammographic screening and at less than 50% participation. It
      is to be hoped that a 20% reduction in mortality can be achieved by further
      increasing the rate of participation.

PMID- 17201349
TI  - [Leiomyoma of the large bowel].
AB  - The authors present a case study of a 48 year old man who was admitted to the
      hospital because of gall stone disease and a palpable abdominal tumour.
      Diagnostic laparoscopy was performed: chronic cholecystitis and an apple size
      tumour were found. The tumour was connected with colon ascendens. Laparotomy was
      performed and both the tumour and gallbladder were removed. The histological
      examination showed leiomyoma of the large bowel.

PMID- 17201348
TI  - [Reconstructive vascular surgery with long-term refrigerated homografts].
AB  - In most cases of vascular repair a graft implantation is needed. Homografts have
      been proven to be suitable conduits when no autogenous graft is available. High
      viability index of vein homograft was confirmed during long term refrigerated
      storage in tissue culture medium, however there was no data of successful
      implanted cases. We report two cases of great saphenous vein (GSV) homograft
      implantation with excellent early results. In the first case graft-popliteal
      bypass was performed with vein homograft after septic ilio-femoral Dacron graft
      explantation and aorto-bifemoral Silver bypass procedure. Septic crossover
      synthetic bypass was replaced with GSV homograft in the second case. Long term
      storage of vein allografts at 4 C is a valuable and cost-effective option for
      revascularization and we propose wide-scale introduction of this method.

PMID- 17201350
TI  - [Rare case of duplex colon invagination].
AB  - Authors recite the records of a patient (26) with a 3-year history of dubious
      abdominal complaints and subileus resulting in numerous examinations and surgical
      observations, with the diagnosis of lower abdominal pain of unknown origin. He
      was acutely admitted to the department of surgery because of haemorrhage ex ano
      and convulsive left abdominal pain. Image creative examinations revealed ileus of
      a probable invagination origin. Partial resection of the transverse colon with
      "end to end" anastomosis was performed. Histology verified Peutz-Jeghers
      syndrome. The authors draw attention to the fact that although invaginations are
      rare above 18 years, when verified preoperatively, elective procedures can be
      carried out with lower risk to the patient.

PMID- 17201351
TI  - Beyond statistical inference: a decision theory for science.
AB  - Traditional null hypothesis significance testing does not yield the probability
      of the null or its alternative and, therefore, cannot logically ground scientific
      decisions. The decision theory proposed here calculates the expected utility of
      an effect on the basis of (1) the probability of replicating it and (2) a utility
      function on its size. It takes significance tests--which place all value on the
      replicability of an effect and none on its magnitude--as a special case, one in
      which the cost of a false positive is revealed to be an order of magnitude
      greater than the value of a true positive. More realistic utility functions
      credit both replicability and effect size, integrating them for a single index of
      merit. The analysis incorporates opportunity cost and is consistent with
      alternate measures of effect size, such as r2 and information transmission, and
      with Bayesian model selection criteria. An alternate formulation is functionally
      equivalent to the formal theory, transparent, and easy to compute.

PMID- 17201352
TI  - Grounding the figure: surface attachment influences figure-ground organization.
AB  - We investigated whether the lower region effect on figure-ground organization
      (Vecera, Vogel, and Woodman, 2002) would generalize to contextual depth planes in
      vertical orientations, as is predicted by a theoretical analysis based on the
      ecological statistics of edges arising from objects that are attached to surfaces
      of support. Observers viewed left/right ambiguous figure-ground displays that
      occluded middle sections of four types of contextual inducers: two types of
      attached, receding, vertical planes (walls) that used linear perspective and/or
      texture gradients to induce perceived depth and two types of similar trapezoidal
      control figures that used either uniform color or random texture to reduce or
      eliminate perceived depth. The results showed a reliable bias toward seeing as
      "figure" the side of the figure-ground display that was attached to the receding
      depth plane, but no such bias for the corresponding side in either of the control
      conditions. The results are interpreted as being consistent with the attachment
      hypothesis that the lower region cue to figure-ground organization results from
      ecological biases in edge interpretation that arise when objects are attached to
      supporting surfaces in the terrestrial gravitational field.

PMID- 17201353
TI  - The effect of novel distractors on performance in focused attention tasks: a
      cognitive-psychophysiological approach.
AB  - In the present study, we examined whether or not novel stimuli affect performance
      in a focused attention task. Participants responded to a central target while an
      irrelevant distractor in the visual display was occasionally changed. In
      Experiment 1, both target and distractor were presented centrally within the
      focus of attention. In Experiment 2, a central target was presented along with an
      irrelevant distractor at a peripheral location, outside the focus of attention.
      Novel distractors were associated with longer latencies and enhanced orienting
      responses (as measured by skin conductance responses) only when presented at an
      attended location. In contrast, as is demonstrated in Experiment 3, the same
      peripheral novel distractors interfered with task performance when they possessed
      task-relevant information. These results indicate that there is a fundamental
      difference between novel stimuli and task-relevant stimuli. Whereas the former
      exert influence only within the focus of attention, the latter affect performance
      even when positioned in an unattended location. Our findings have important
      implications for the operation of visual attention.

PMID- 17201354
TI  - Color singleton pop-out does not always poop out: an alternative to visual
      search.
AB  - Folk psychology suggests that when an observer views a scene, a unique item will
      stand out and draw attention to itself. This belief stands in contrast to
      numerous studies in visual search that have found that a unique target item
      (e.g., a unique color) is not identified more quickly than a nonunique target. We
      hypothesized that this finding is the result of task demands of visual search,
      and that when the task does not involve visual search, uniqueness will pop out.
      We tested this hypothesis in a task in which observers were presented an array of
      letters and asked to respond aloud, as quickly as possible, with the identity of
      any one of the letters. The observers were significantly more likely to respond
      with a uniquely colored letter than would be expected by chance. In a task in
      which observers blurt out the first thing that they see, unique pop-out does not
      poop out.

PMID- 17201355
TI  - Feature bindings endure without attention: evidence from an explicit recall task.
AB  - Are integrated objects the unit of capacity of visual working memory, or is
      continued attention needed to maintain bindings between independently stored
      features? In a delayed recall task, participants reported the color and shape of
      a probed item from a memory array. During the delay, attention was manipulated
      with an exogenous cue. Recall was elevated at validly cued positions, indicating
      that the cue affected item memory. On invalid trials, participants most
      frequently recalled either both features (perfect object memory) or neither of
      the two features (no object memory); the frequency with which only one feature
      was recalled was significantly lower than predicted by feature independence as
      determined in a single-feature recall task. These data do not support the view
      that features are remembered independently when attention is withdrawn. Instead,
      integrated objects are stored in visual working memory without need for continued
      attention.

PMID- 17201356
TI  - Change blindness and the primacy of object appearance.
AB  - A large body of work suggests that the visual system is particularly sensitive to
      the appearance of new objects. This is based partly on evidence from visual
      search studies showing that onsets capture attention whereas many other types of
      visual event do not. Recently, however, the notion that object onset has a
      special status in visual attention has been challenged. For instance, an object
      that looms toward an observer has also been shown to capture attention. In two
      experiments, we investigated whether onset receives processing priority over
      looming. Observers performed a change detection task in which one of the display
      objects either loomed or receded, or a new object appeared. Results showed that
      looming objects were more resistant to change blindness than receding objects.
      Crucially, however, the appearance of a new object was less susceptible to change
      blindness than both looming and receding. We argue that the visual system is
      particularly sensitive to object onsets.

PMID- 17201357
TI  - Two noncontiguous locations can be attended concurrently: evidence from the
      attentional blink.
AB  - When two targets (T1 and T2) are inserted in a rapid stream of visual distractors
      (RSVP), detection/ identification accuracy of T2 is impaired at intertarget lags
      shorter than about 500 msec. This phenomenon, the attentional blink (AB), has
      been regarded as a hallmark of the inability of the visual system to process
      multiple items. Yet, paradoxically, the AB is much reduced when T2 is presented
      directly after T1 (known as lag-1 sparing). Because lag-1 sparing is said to
      depend on observers' spatial attention being set to process the first target, we
      predicted that if observers are set to monitor two RSVP streams, they could
      process more than two items; that is, two instances of lag-1 sparing would be
      obtained concurrently. The results of three experiments indicated that this was
      the case. When observers searched for two targets in each of two synchronized
      RSVP streams, lag-1 sparing occurred concurrently in both streams. These results
      suggest that the visual system can handle up to four items at one moment under
      RSVP circumstances.

PMID- 17201358
TI  - Task-irrelevant visual motion and flicker attenuate the attentional blink.
AB  - Our reduced ability to correctly report two sequentially presented targets is
      seen in the robust effect known as the attentional blink (AB; Raymond, Shapiro,
      and Arnell, 1992). One recent report (Olivers and Nieuwenhuis, 2005) strikingly
      reveals the AB to be virtually abolished when non-task-demanding music occurs in
      the background. The authors suggest that a diffuse attentional state is the
      mediating factor. Here, we seek to broaden the finding's generality by
      determining if task-irrelevant visual motion and flicker also attenuate the AB.
      In our experiments, the AB task was presented together with a background field of
      moving dots that could move away from or toward the central AB task, or flicker.
      In the control condition, the dots remained static. The AB was attenuated--though
      to different degrees--in all experimental conditions, but not in the static
      condition. Our findings add to the generality of the previous conclusions, and we
      emphasize an account based on the overallocation of attention.

PMID- 17201359
TI  - Spatial working memory and inhibition of return.
AB  - Recently we showed that maintaining a location in spatial working memory affects
      saccadic eye movement trajectories, in that the eyes deviate away from the
      remembered location (Theeuwes, Olivers, and Chizk, 2005). Such saccade deviations
      are assumed to be the result of inhibitory processes within the oculomotor
      system. The present study investigated whether this inhibition is related to the
      phenomenon of inhibition of return (IOR), the relatively slow selection of
      previously attended locations as compared with new locations. The results show
      that the size of IOR to a location was not affected by whether or not the
      location was kept in working memory, but the size of the saccade trajectory
      deviation was affected. We conclude that inhibiting working memory-related eye
      movement activity is not the same as inhibiting a previously attended location in
      space.

PMID- 17201361
TI  - Distraction as a determinant of processing speed.
AB  - Processing speed is often described as a fundamental resource determining
      individual (e.g., I.Q.) and group (e.g., developmental) differences in cognition.
      However, most tests that measure speed present many items on a single page.
      Because many groups with slowed responding are also distractible, we compared
      younger and older adults on high-distraction (i.e., standard) versus low
      distraction versions of two classic speed tasks. Reducing distraction improved
      the performance of older adults but had little or no effect on younger adults,
      suggesting that the ability to limit attentional access to task-relevant
      information can affect performance on tests designed to measure processing speed.

PMID- 17201360
TI  - Mental rubbernecking to negative information depends on task context.
AB  - We previously demonstrated mental rubbernecking during the simple cognitive act
      of refreshing a just activated representation. Participants saw two neutral and
      one negative word presented simultaneously and, 425 msec later, were cued to
      mentally refresh (i.e., think of) one of the no-longer-present words. They were
      slower to refresh a neutral word than the negative word (Johnson et al., 2005,
      Experiment 6A). The present experiments extended that work by showing mental
      rubbernecking when negative items were sometimes the target of refreshing, but
      not when negative items were present but never the target of refreshing,
      indicating that expectations influence mental rubbernecking. How expectations
      might modulate the impact of emotional distraction is discussed.

PMID- 17201363
TI  - Cross-domain transfer of quantitative discriminations: is it all a matter of
      proportion?
AB  - Meck and Church (1983) estimated a 5:1 scale factor relating the mental
      magnitudes representing number to the mental magnitudes representing duration. We
      repeated their experiment with human subjects. We obtained transfer regardless of
      the objective scaling between the ranges; a 5:1 scaling for number versus
      duration (measured in seconds) was not necessary. We obtained transfer even when
      the proportions between the endpoints of the number range were different. We
      conclude that, at least in human subjects, transfer from a discrimination based
      on continuous quantity (duration) to a discrimination based on discrete quantity
      (number) is mediated by the cross-domain comparability of within-domain
      proportions. The results of our second and third experiments also suggest that
      the subjects compare a probe with a criterion determined by the range of stimuli
      tested rather than by trial-specific referents, in accordance with the
      pseudologistic model of Killeen, Fetterman, and Bizo (1997).

PMID- 17201364
TI  - Attention modulates the learning of multiple contingencies.
AB  - We employed a novel version of the serial reaction time task to test the idea
      that human implicit learning allows the simultaneous learning of multiple
      independent contingencies and that this learning may proceed in the absence of
      attention. Using probabilistic sequences, we showed that both a primary sequence
      (the focus of the experimental task) and a statistically independent secondary
      sequence could be learned across 4,800 target localization trials, provided the
      perceptual load of the primary task was low. However, learning of the secondary
      sequence was abolished under conditions of high perceptual load. These findings
      suggest that there are attentional limitations on the learning of multiple
      contingencies.

PMID- 17201362
TI  - Aging and individual differences in rapid two-choice decisions.
AB  - The effects of aging on performance were examined in signal detection, letter
      discrimination, brightness discrimination, and recognition memory, with each
      subject tested on all four tasks. Ratcliff's (1978) diffusion model was fit to
      the data for each subject for each task, and it provided a good account of
      accuracy and the distributions of correct and error response times. The model's
      analysis of the components of processing showed that aging had three main
      effects: The nondecision components of processing were slower and the decision
      criteria were more conservative for 60- to 74-year-old and 75- to 85-year-old
      subjects than for college students, but the quality of the evidence on which
      decisions were based was as good for the older subjects as for college students
      on some of the tasks. Individual differences among subjects in components of
      processing tended to be preserved across the tasks, as was shown by strong
      correlations across the tasks in the parameters of the model that represent the
      components of processing. For example, if the evidence on which a subject's
      decisions were based was good in one task, it tended to be good in all four
      tasks.

PMID- 17201365
TI  - Visual noise reveals category representations.
AB  - How are categories represented in human memory? Exemplar models assume that a
      category is represented by individual instances from that category that have been
      experienced. More generally, a category might be represented by multiple
      templates stored in memory. A new item is classified according to its similarity
      to these templates. Prototype models represent a category with a single summary
      abstraction (i.e., a single template), often the central tendency of the
      experienced items. A new item is classified according to its similarity to these
      category prototypes. Here, we show how a technique for correlating observers'
      responses with external noise can be used not only to distinguish single- from
      multiple-template representations, but also to induce the form of these
      templates. The technique is applied to two tasks requiring categorization of
      simple visual patterns; the results demonstrate that observers used multiple
      traces to represent their categories, and thus highlight the procedure's
      potential for use in more complex settings.

PMID- 17201366
TI  - Perceptual learning in contrast detection: presence and cost of shifts in
      response criteria.
AB  - Contemporary theoretical accounts of perceptual learning typically assume that
      observers are either unbiased or stably biased across the course of learning.
      However, standard methods for estimating thresholds, as they are typically used,
      do not allow this assumption to be tested. We present an approach that allows for
      this test specific to perceptual learning for contrast detection. We show that
      reliable decreases in detection thresholds and increases in hit rates are not
      uniformly accompanied by reliable increases in sensitivity (d'), but are
      regularly accompanied by reliable liberal shifts in response criteria (c). In
      addition, we estimate the extent to which sensitivity could have increased in the
      absence of these liberal shifts. The results pose a challenge to the assumption
      that perceptual learning has limited or no impact on response criteria.

PMID- 17201367
TI  - Extinction of conditioned inhibition through nonreinforced presentation of the
      inhibitor.
AB  - In previous studies that have tried to extinguish conditioned inhibition through
      nonreinforced presentations of the inhibitor, researchers have repeatedly failed
      to find evidence for such extinction. The present study revealed that extinction
      can be achieved through nonreinforcement of the inhibitor, depending on
      properties of the reinforcer. In a human causal learning experiment, we found
      complete extinction in a scenario in which the reinforcer could take on negative
      values. Thereby, this scenario reflected the assumed symmetrical continuum on
      which associative strength can vary, according to the Rescorla-Wagner theory of
      associative learning. In contrast to this, the inhibitory cue retained its
      inhibitory potential in another condition, in which the scenario did not allow
      negative values of the reinforcer.

PMID- 17201368
TI  - Additive and interactive effects of word frequency and masked repetition in the
      lexical decision task.
AB  - In previous studies, additive effects of masked repetition and word frequency on
      lexical decision latency have been reported. This additive pattern was replicated
      in Experiment 1 with the use of low-frequency words (range, 1-7 per million)
      selected at random. In contrast, in Experiment 2, in which low-frequency words
      known to be familiar to the subjects were used, the masked repetition priming
      effect was greater for low-frequency than for high-frequency words. It is
      suggested that the absence of an interaction between masked repetition and
      frequency observed in previous studies and in the present Experiment 1 was due to
      the fact that very-low-frequency words often have an unstable representation in
      the subjects' lexicon and, consequently, sometimes fail to produce repetition
      priming effects in full.

PMID- 17201369
TI  - On the time course of letter perception: a masked priming ERP investigation.
AB  - In an experiment measuring event-related brain potentials (ERPs), single-letter
      targets were preceded by briefly presented masked letter primes. Name and case
      consistency were manipulated across primes and targets so that the prime was
      either the same letter as the target (or not), and was presented in the same case
      as the target (or not). Separate analyses were performed for letters whose upper-
      and lowercase forms had similar features (or not). The results revealed an effect
      of prime-target visual similarity between 120 and 180 msec, an effect of case
      specific letter identity between 180 and 220 msec, and an effect of case
      independent letter identity between 220 and 300 msec. We argue that these ERP
      results reflect processing in a hierarchical system for letter recognition that
      involves both case-specific and case-independent representations of alphabetic
      stimuli.

PMID- 17201370
TI  - Interpreting spatial terms involves simulating interactions.
AB  - Recent research in spatial language has demonstrated that the interpretation of a
      spatial term depends not only on the geometry of the configuration of the objects
      being spatially related, but also on extrageometric information, including
      information about the objects and their interaction. Such effects could emerge
      from activation of general knowledge of the association between the objects;
      thus, they should be widely observed. In contrast, they could be more restricted,
      emerging only in situations in which the spatial language task positions objects
      in a manner that is consistent with a simulation of their interaction. In two
      experiments, we test each of these ideas and demonstrate that extrageometric
      information augments geometric information in the interpretation of spatial terms
      only when the situation enables the interaction.

PMID- 17201371
TI  - Humans' folk physics is not enough to explain variations in their tool-using
      behavior.
AB  - Two experiments examined adult humans' folk physics (i.e., their naturally
      occurring and spontaneous understanding of the physical world) using variations
      of trap-table problems used to study chimpanzees' folk physics. When presented
      with these problems, people unnecessarily avoided retrieving a reward by pulling
      a rake on the side of a table with a trapping hole--even though it was highly
      unlikely that the hole would trap the reward. However, when the distance between
      the reward and the trap was sufficiently large and the distance that the reward
      had to travel to be retrieved was sufficiently short, people preferred to
      retrieve a reward by pulling the rake on the side of the table with the trap.
      These results underscore that behavior during tool-use tasks has many possible
      causes, only one of which might be a subject's folk physics.

PMID- 17201372
TI  - Expertise and its embodiment: examining the impact of sensorimotor skill
      expertise on the representation of action-related text.
AB  - In two experiments, we explored how novice and expert athletes represent the
      everyday and sport-specific objects and actions that they read about. Novice and
      expert ice hockey players (Experiment 1) and football players (Experiment 2) read
      sentences describing everyday or sport-specific situations and then judged
      whether a pictured item (either matching the action implied in the previous
      sentence or not) was mentioned in the preceding sentence. The sentences in
      Experiment 1 consisted of everyday and hockey-specific scenarios. The sentences
      in Experiment 2 depicted football scenarios implying football-specific or non
      football-specific actions anyone might perform. Everyone responded most quickly
      to items that matched the sentence-implied actions for everyday and non-sport
      specific actions. Only athletes showed this effect for their respective sport
      specific scenarios. Differentiating between the same item in different action
      orientations is thought to be driven by embodied knowledge containing the
      sensorimotor characteristics of what one is reading about. We show that
      possessing this type of representation depends on experience interacting with
      objects and performing the actions in question.

PMID- 17201374
TI  - The planning and execution of short auditory sequences.
AB  - Action planning, but not action execution, in speeded tasks is typically faster
      when responses and their effects are compatible than when they are incompatible.
      We tested whether response-effect compatibility (REC) affects the execution of
      music-like sequential actions that require temporal regularity rather than
      rapidity. Musicians responded to metronomic visual stimuli by producing sequences
      of three taps at a specific tempo on three vertically aligned keys. Each tap
      triggered a tone. Key-to-tone mapping was either compatible or incompatible in
      terms of spatial height and pitch height. The results indicated that tap timing
      was more accurate with compatible than with incompatible mappings, both for taps
      produced before (Tap 1) and after (Taps 2 and 3) the onset of auditory feedback.
      Thus, the observed influence of REC on action execution was not due exclusively
      to actual auditory feedback. The anticipation of distal action effects may be
      involved in planning the dynamics of temporally precise movements.

PMID- 17201373
TI  - An event-based account of coordination stability.
AB  - Constraints underlying bimanual coordination have traditionally been explained by
      dynamic interactions between the effectors. However, the present experiments
      demonstrate that a fundamental constraint on bimanual performance is the manner
      in which task goals are represented. In Experiment 1, participants vocalized
      during in-phase and anti-phase bimanual movements. As expected, most participants
      spontaneously exhibited temporal coupling between the manual and vocal responses.
      However, the form of coupling differed for the in-phase and anti-phase
      conditions. For anti-phase movements, there was a strong bias to produce two
      vocalizations per cycle; for in-phase movements, participants were equally likely
      to produce one or two vocalizations per cycle. We hypothesized that the
      spontaneous vocalizations probed the cognitive representation of the task, and
      the results indicated that anti-phase movements did entail a more complex event
      structure than in-phase movements did. In Experiment 2, we manipulated the event
      structure by having participants vocalize either once or twice per hand cycle. As
      predicted, coordination stability was reduced when the event structure was more
      complex.

PMID- 17201375
TI  - Evidence for time-based models of free recall.
AB  - Is memory temporally organized? According to temporal distinctiveness models of
      memory, temporally isolated items should be better remembered than temporally
      crowded items in free recall tasks. Here, we tested this class of model by
      varying the temporal isolation of items either predictably (Experiment 1) or
      unpredictably (Experiment 2) in a free recall task. In both experiments, item
      recall probability increased as a function of the temporal gaps both before and
      after the item. The results are taken as support for temporal distinctiveness
      models of memory, in which items are represented and recalled in terms of their
      positions along a temporal dimension.

PMID- 17201376
TI  - Word frequency and the mixed-list paradox in immediate and delayed serial recall.
AB  - In free recall tasks, when low- and high-frequency items are mixed within the to
      be-remembered lists, the usual recall advantage found for high-frequency words is
      eliminated or reversed. Recently, this mixed-list paradox has also been
      demonstrated for short-term serial recall (Hulme, Stuart, Brown, and Morin,
      2003). Although a number of theoretical interpretations of this mixed-list
      paradox have been proposed, researchers have also suggested that it could simply
      be a result of participant-controlled strategies (M. J. Watkins, LeCompte, and
      Kim, 2000). The present study was designed to assess whether this explanation
      could be applied to immediate and delayed serial recall. The results showed that
      high-frequency words were recalled better than low-frequency words in pure lists,
      but that this effect was eliminated in mixed lists, whether they were given under
      intentional or incidental learning conditions. This pattern suggests that the
      mixed-list paradox cannot be explained by participant-controlled strategies.

PMID- 17201378
TI  - 1/f noise in human cognition: is it ubiquitous, and what does it mean?
AB  - Researchers in psychology are paying increasing attention to temporal
      correlations in performance on cognitive tasks. Recently, Thornton and Gilden
      (2005) introduced a spectral method for analyzing psychological time series; in
      particular, this method is tailored to distinguish transient serial correlations
      from the persistent correlations characterized by 1/f noise. Thornton and Gilden
      applied their method to word-naming data to support the claimed ubiquity of 1/f
      noise in psychological time series. We argue that a previously presented method
      for distinguishing transient and persistent correlations (e.g., Wagenmakers,
      Farrell, and Ratcliff, 2004) compares favorably with the new method presented by
      Thornton and Gilden. We apply Thornton and Gilden's method to time series from a
      range of cognitive tasks and show that 1/f noise is not a ubiquitous property of
      psychological time series. Finally, we assess the theoretical developments in
      this area and argue that the development of well-specified models of the
      principles or mechanisms of human cognition giving rise to 1/f noise is long
      overdue.

PMID- 17201377
TI  - The influence of an external symbol system on number parity representation, or
      what's odd about 6?
AB  - The aim of this study was to investigate whether language-specific properties
      influence mental number processing. German Sign Language (DGS) numbers differ
      from those in spoken German not only in terms of modality but also in their basic
      language structure. A group of 20 congenitally deaf German signers participated
      in a number parity (odd/even) judgment task with DGS and printed German number
      words. The results indicated that two-handed DGS number signs are processed in a
      decomposed way. This language-specific effect also generalized to another
      linguistic number notation, German number words, but not to Arabic digit
      notation. These differences are discussed with respect to two possible routes to
      number parity.

PMID- 17201380
TI  - Solvation of H3O+ by phenol: hydrogen bonding vs pi complexation.
AB  - Ab initio calculations at the second-order Moller-Plesset perturbation theoretic
      level have been carried out to study the solvation of protonated water by phenol
      molecules. The results show that in addition to classical O-H...O hydrogen bonds,
      C-H...O, pi...H-O, and pi...H-C bonds are also formed, thus stabilizing the
      H3O+(C(6)H(5)OH)3 complex.

PMID- 17201381
TI  - Molecular constants of aluminum monohalides: caveats for computations of simple
      inorganic molecules.
AB  - Quantum chemical calculations have become an everyday tool in chemistry. There
      are commercial program packages and downloadable basis sets for most needs.
      However, many chemists rarely go beyond the routine use of these programs,
      rarely, if ever, checking the original references for basis sets. In this letter,
      we point out some of the pitfalls of such an approach. Structural parameters of
      the aluminum-monohalides, AlF, AlCl, AlBr, and AlI, have been calculated using
      the Gaussian 03 program package and different basis set combinations.

PMID- 17201382
TI  - Heavy ion radiolysis of liquid pyridine.
AB  - The radiation chemical yields of the main products produced in liquid pyridine
      radiolysis (molecular hydrogen and dipyridyl) have been examined as a function of
      particle linear energy transfer (LET) with protons, helium ions, and carbon ions
      of a few to 30 MeV and compared to gamma-radiolysis published in a previous work
      (J. Phys. Chem. A 2005, 109, 461). Anthracene and biphenyl scavenging techniques
      have been used to clarify the role of the triplet excited state. An increase in
      triplet scavenger concentration leads to a decrease in pyridine triplet excited
      state with a concurrent decrease in dipyridyl, but formation of the latter does
      not primarily involve pyridyl radicals expected to be produced in the
      decomposition of the triplet excited state. A decrease in the yield of dipyridyl
      and an increase in molecular hydrogen are observed with increasing track average
      LET. The dipyridyl yield with 10 MeV carbon ions is 0.20 molecules/100 eV, which
      is only 16% of that of observed with gamma-rays. The low yield of dipyridyl with
      carbon ions is attributed to intratrack triplet-triplet (T-T) annihilation
      processes due to the increase in local triplet excited-state concentrations with
      increasing LET. An increasing yield of molecular hydrogen with increasing LET is
      probably due to an increase in the formation and subsequent decay of singlet
      excited states produced by the T-T annihilation. A complete mechanism for the
      radiolysis of liquid pyridine is presented.

PMID- 17201383
TI  - Dissociation dynamics of sequential ionic reactions: heats of formation of tri-,
      di-, and monoethylphosphine.
AB  - The sequential ethene (C2H4) loss channels of energy-selected ethylphosphine ions
      have been studied using threshold photoelectron photoion coincidence (TPEPICO)
      spectroscopy in which ion time-of-flight (TOF) distributions are recorded as a
      function of the photon energy. The ion TOF distributions and breakdown diagrams
      have been modeled in terms of the statistical RRKM theory for unimolecular
      reactions, providing 0 K dissociation onsets, E0, for the ethene loss channels.
      Three RRKM curves were used to model the five measurements, since two of the
      reactions differ only by the internal energy of the parent ion. This series of
      dissociations provides a detailed check of the calculation of the product energy
      distribution for sequential reactions. From the determined E0's, the heats of
      formation of several ethylphosphine neutrals and ions have been determined:
      Delta(f)H degrees 298K[P(C(2)H(5))3] = -152.7 +/- 2.8 kJ/mol, Delta(f)H degrees
      298K[P(C(2)H(5))3+] = 571.6 +/- 4.0 kJ/mol, Delta(f)H degrees 298K[HP(C(2)H(5))2]
      = -89.6 +/- 2.1 kJ/mol, Delta(f)H degrees 298K[HP(C(2)H(5))2+] = 669.9 +/- 2.5
      kJ/mol, Delta(f)H degrees 298K[H(2)PC(2)H(5)] = -36.5 +/- 1.5 kJ/mol, Delta(f)H
      degrees 298K[H(2)PC(2)H(5)+] = 784.0 +/- 1.9 kJ/mol. These values have been
      supported by G2 and G3 calculations using isodesmic reactions. Coupled cluster
      calculations have been used to show that the C2H4 loss channel, which involves a
      hydrogen transfer step, proceeds without a reverse energy barrier.

PMID- 17201385
TI  - Probing the structure and bonding in Al6N- and Al6N by photoelectron spectroscopy
      and ab initio calculations.
AB  - The electronic and geometrical structure of a nitrogen-doped Al6- cluster (Al6N-)
      is investigated using photoelectron spectroscopy and ab initio calculations.
      Photoelectron spectra of Al6N- have been obtained at three photon energies with
      seven resolved spectral features. The electron affinity of Al6N has been
      determined to be 2.58 +/- 0.04 eV. Global minimum structure searches for A6N- and
      its corresponding neutral form are performed using several theoretical methods.
      Vertical electron detachment energies, calculated using three different methods
      for the lowest energy structure and a low-lying isomer, are compared with the
      experimental data. The ground-state structure of Al6N- is established from the
      joint experimental and theoretical study to consist of an Al2 dimer bonded to the
      top of a quasi-planar tetracoordinated N unit, Al4N-, or it can be viewed as a
      distorted trigonal prism structure with the N atom bonded in one of the prism
      faces. For neutral Al6N, three low-lying isomers are found to compete for the
      global minimum, two of which are built from the tetracoordinated Al4N unit. The
      chemical bonding in Al6N- is discussed on the basis of molecular orbital and
      natural bond analyses.

PMID- 17201384
TI  - The role of the beta-ionone ring in the photochemical reaction of rhodopsin.
AB  - Time-dependent density functional theory (TDDFT) calculations on the
      photoabsorption process of the 11-cis retinal protonated Schiff base (PSB)
      chromophore show that the Franck-Condon relaxation of the first excited state of
      the chromophore involves a torsional twist motion of the beta-ionone ring
      relative to the conjugated retinyl chain. For the ground state, the beta-ionone
      ring and the retinyl chain of the free retinal PSB chromophore form a -40 degrees
      dihedral angle as compared to -94 degrees for the first excited state. The double
      bonds of the retinal are shorter for the fully optimized structure of the excited
      state than for the ground state suggesting a higher cis-trans isomerization
      barrier for the excited state than for the ground state. According to the present
      TDDFT calculations, the excitation of the retinal PSB chromophore does not
      primarily lead to a reaction along the cis-trans torsional coordinate at the C11
      C12 bond. The activation of the isomerization center seems to occur at a later
      stage of the photo reaction. The results obtained at the TDDFT level are
      supported by second-order Moller-Plesset (MP2) and approximate singles and
      doubles-coupled cluster (CC2) calculations on retinal chromophore models; the MP2
      and CC2 calculations yield for them qualitatively the same ground state and
      excited-state structures as obtained in the density functional theory and TDDFT
      calculations.

PMID- 17201386
TI  - Electronic and geometric stabilities of clusters with transition metal
      encapsulated by silicon.
AB  - Silicon clusters mixed with a transition metal atom, MSin, were generated by a
      double-laser vaporization method, and the electronic and geometric stabilities
      for the resulting clusters with transition metal encapsulated by silicon were
      examined experimentally. By means of a systematic doping with transition metal
      atoms of groups 3, 4, and 5 (M = Sc, Y, Lu, Ti, Zr, Hf, V, Nb, and Ta), followed
      by changes of charge states, we explored the use of an electronic closing of a
      silicon caged cluster and variations in its cavity size to facilitate metal-atom
      encapsulation. Results obtained by mass spectrometry, anion photoelectron
      spectroscopy, and adsorption reactivity toward H2O show that the neutral cluster
      doped with a group 4 atom features an electronic and a geometric closing at n =
      16. The MSi(16) cluster with a group 4 atom undergoes an electronic change in (i)
      the number of valence electrons when the metal atom is substituted by the
      neighboring metals with a group 3 or 5 atom and in (ii) atomic radii with the
      substitution of the same group elements of Zr and Hf. The reactivity of a halogen
      atom with the MSi(16) clusters reveals that VSi(16)F forms a superatom complex
      with ionic bonding.

PMID- 17201387
TI  - Ground and excited state resonance Raman spectra of an azacrown-substituted
      [(bpy)Re(CO)3L]+ complex: characterization of excited states, determination of
      structure and bonding, and observation of metal cation release from the azacrown.
AB  - A [(bpy)Re(CO)3L+] complex (bpy = 2,2'-bipyridine) in which L contains a phenyl
      azacrown ether that is attached to Re via an amidopyridyl linking group has been
      studied by steady state and nanosecond time-resolved resonance Raman
      spectroscopy. Vibrational band assignments have been aided by studies of model
      complexes in which a similar electron-donating dimethylamino group replaces the
      azacrown or in which an electron-donor group is absent, and by density functional
      theory calculations. The ground state resonance Raman spectra show nu(bpy) and
      nu(CO) bands of the (bpy)Re(CO)3 group when excitation is exclusively in
      resonance with the Re --> bpy metal-to-ligand charge-transfer (MLCT) transition,
      whereas L ligand bands are dominant when it is in resonance with the strong intra
      ligand charge-transfer (ILCT) transition present for L ligands with electron
      donor groups. Transient resonance Raman (RR) spectra obtained on single color
      (385 nm) pulsed excitation of the complexes in which an electron-donor group is
      absent show bpy*- bands of the MLCT excited state, whereas those of the complexes
      with electron-donor groups show both bpy*- bands and a down-shifted nu(CO) band
      that together are characteristic of an L-to-bpy ligand-to-ligand charge-transfer
      (LLCT) excited state. Samples in which a metal cation (Li+, Na+, Ca2+, Ba2+) is
      bound to the azacrown in the ground state show bands from both excited states,
      consistent with a mechanism in which the LLCT state forms after metal cation
      release from the MLCT state. Nanosecond time-resolved RR spectra from two-color
      (355 nm pump, 500 nm probe) experiments on the electron-donor systems show L
      ligand bands characteristic of the LLCT state; the same bands are observed from
      samples in which a metal cation is bound to the azacrown in the ground state, and
      their time dependence is consistent with the proposed mechanism in which the rate
      constant for ion release in the MLCT state depends on the identity of the metal
      cation.

PMID- 17201388
TI  - High-pressure vibrational spectroscopy of energetic materials: hexahydro-1,3,5
      trinitro-1,3,5-triazine.
AB  - Vibrational spectroscopy has been used to investigate the room-temperature high
      pressure phases of the energetic material hexahydro-1,3,5-trinitro-1,3,5-triazine
      (RDX). The pressure-induced alterations in the spectral profiles were studied in
      a compression sequence to 30.2 GPa using Raman spectroscopy and to 26.6 GPa using
      far-infrared spectroscopy. At pressures near 4.0 GPa, several changes become
      immediately apparent in the Raman spectrum, such as large frequency shifts, mode
      splittings, and intensity changes, which are associated with a phase transition
      from alpha-RDX to gamma-RDX. Our study extends the kinetic stability of gamma-RDX
      to pressures near 18.0 GPa. Evidence for a new phase was found at pressures
      between 17.8 and 18.8 GPa and is based on the appearance of new vibrational bands
      and associated changes in intensity patterns. The new phase has vibrational
      characteristics that are similar to those of beta-RDX, suggesting the two
      polymorphs share a related crystal structure.

PMID- 17201389
TI  - Matrix isolation infrared spectroscopic and theoretical study of noble gas
      coordinated rhodium-dioxygen complexes.
AB  - Reactions of rhodium atoms with dioxygen molecules in solid argon have been
      investigated using matrix isolation infrared absorption spectroscopy. The rhodium
      dioxygen complexes, Rh(eta2-O2), Rh(eta2-O2)2, and Rh(eta2-O2)2(eta1-OO), are
      produced spontaneously on annealing. The Rh(eta2-O2) complex rearranges to the
      inserted RhO2 molecule under visible light irradiation. Experiments doped with
      xenon in argon show that the rhodium-dioxygen complexes are coordinated by one or
      two noble gas atoms in solid noble gas matrixes. Hence, the Rh(eta2-O2), Rh(eta2
      O2)2, and Rh(eta2-O2)2(eta1-OO) molecules trapped in solid noble gas matrixes
      should be regarded as the Rh(eta2-O2)(Ng)2, Rh(eta2-O2)2(Ng)2, and Rh(eta2
      O2)2(eta1-OO)(Ng) (Ng = Ar or Xe) complexes. The product absorptions are
      identified on the basis of isotopic substitution and density functional theory
      calculations.

PMID- 17201390
TI  - Ionization of aromatic sulfides in nonpolar media: free vs reaction-controlled
      electron transfer.
AB  - The primary products of the bimolecular free electron transfer (FET) from
      aromatic sulfides (PhSCH2Ph, PhSCHPh2, PhSCPh3) to n-butyl chloride radical
      cations are two radical cation conformers: a dissociative and a metastable one.
      In analogy with formerly studied donor systems, this result seems to reflect
      femtosecond oscillations in the ground state of the sulfides such as torsion
      motions around the Ar-S bond. This motion is accompanied by a marked electron
      fluctuation within the HOMO (or the n) orbitals. The FET products observed in the
      nanosecond time scale such as the metastable sulfide radical cations (Ar-S
      CR3*+), the dissociation products R3C+; and R3C*, and their (experimentally)
      nondetectable counterparts Ar-S* as well as Ar-S+ can be understood with the
      simplified assumption of two extreme conformations, namely a planar and a twisted
      donor molecule. Using mediator radical cations (benzene, butylbenzene, biphenyl),
      the stepwise reduction of the free energy of the electron transfer from -DeltaH =
      2.5 to <or=0.5 eV changes the dissociation pattern of the sulfide radical cations
      toward a uniform product such as the metastable sulfide radical cation. From
      that, we tentatively interpret the mechanism of the studied electron transfer as
      diffusion-controlled (collision-determined FET) at higher -DeltaH values and as
      reaction-controlled at -DeltaH below 0.5 eV.

PMID- 17201391
TI  - Reaction of O2 with the hydrogen atom in water up to 350 degrees C.
AB  - The reaction of the H* atom with O2, giving the hydroperoxyl HO2* radical, has
      been investigated in pressurized water up to 350 degrees C using pulse radiolysis
      and deep-UV transient absorption spectroscopy. The reaction rate behavior is
      highly non-Arrhenius, with near diffusion-limited behavior at room temperature,
      increasing to a near constant limiting value of approximately 5 x 10(10) M(-1) s(
      1) above 250 degrees C. The high-temperature rate constant is in near-perfect
      agreement with experimental extrapolations and ab initio calculations of the gas
      phase high-pressure limiting rate. As part of the study, reaction of the OH*
      radical with H2 has been reevaluated at 350 degrees C, giving a rate constant of
      (6.0 +/- 0.5) x 10(8) M(-1) s(-1). The mechanism of the H* atom reaction with the
      HO2* radical is also investigated and discussed.

PMID- 17201392
TI  - Experimental and theoretical studies of the reaction of the OH radical with alkyl
      sulfides: 1. Direct observations of the formation of the OH-DMS adduct-pressure
      dependence of the forward rate of addition and development of a predictive
      expression at low temperature.
AB  - A pulsed laser photolysis-pulsed laser-induced fluorescence (PLP-PLIF) system was
      employed to study the kinetics and mechanisms of reactions (1) OH + h6-DMS -->
      products and (2) OH + d6-DMS --> products. We report direct observations of the
      rate coefficients for the formation and dissociation of the h6-OHDMS and d6-OHDMS
      adducts over the pressure range 50-650 Torr and between 240 and 245 K, together
      with measurements of the oxygen dependence of the effective rate coefficients for
      reactions 1 and 2 under similar conditions. The effective rate coefficients
      increased as a function of O2 concentration reaching their limiting values in
      each case. The values of the adduct formation rate, obtained from the O2
      dependencies, were in excellent agreement with values determined from direct
      observation of adduct equilibration in N2. OH regeneration is insignificant. The
      rate coefficients for the formation of the adduct isotopomers showed slight
      differences in their falloff behavior and do not approach the high-pressure limit
      in either case. The equilibrium constants obtained show no dependence on
      isotopomer and are in good agreement with previous work. A "second-law" analysis
      of the temperature dependence of the equilibrium constant gives an adduct bond
      strength (DeltaH degrees =-10.9 +/- 1.0 kcal mol(-1)), also in good agreement
      with previously reported values. Using the entropy calculated from the ab initio
      vibrational frequencies, we obtain a "third-law" value for the reaction enthalpy
      at 240 K, DeltaH(240K) degrees = -10.5 kcal mol(-1) in good agreement with the
      other approach. The rate coefficient for the reactions of the adducts with O2 was
      obtained from an analysis of the O2 dependence and was determined to be 6.3 +/-
      1.2 x 10(-13) cm3 molecule(-1) s(-1), with no dependence on pressure or
      isotopomer. The pressure and temperature dependence for all of the elementary
      processes in the initial steps of the dimethylsulfide (DMS) oxidation mechanism
      have been characterized in the range 238-245 K, allowing the formulation of an
      expression which can be used to calculate the effective rate coefficient for
      reaction 1 at any pressure and oxygen concentration. The expression can calculate
      the effective rate coefficient for reaction 1 to +/- 40% over the range 220-260
      K, with the largest errors at the extremes of this range. Gaussian 03 has been
      used to calculate the structure of the OH-DMS adduct and its deuterated
      isotopomer. We find similar bound structures for both isotopomers. The calculated
      enthalpies of formation of the adducts are lower than the experimentally
      determined values.

PMID- 17201393
TI  - Charge localization in stacked radical cation DNA base pairs and the benzene
      dimer studied by self-interaction corrected density-functional theory.
AB  - The incomplete cancellation of the electron self-interaction can be a serious
      shortcoming of density-functional theory especially when treating odd-electron
      systems. In this work, several popular and potentially viable correction schemes
      are applied in order to characterize the electronic structure of stacked
      molecular pairs, consisting of a neutral molecule and adjacent radical cation, as
      a function of separation distance. The unphysical sharing of the positive charge
      between adjacent molecules separated by 6-7 A is corrected for by applying a new
      empirical scheme proposed by VandeVondele and Sprik [Phys. Chem. Chem. Phys.
      2005, 7, 1363] with a unique choice of parameters. This method is subsequently
      applied to characterize the electronic structure of two neighboring guanines
      excised from a canonical Arnott B-DNA structure and will be used in future
      investigations of certain model DNA fibers.

PMID- 17201394
TI  - Theoretical prediction of the heats of formation of C2H5O* radicals derived from
      ethanol and of the kinetics of beta-C-C scission in the ethoxy radical.
AB  - Thermochemical parameters of three C(2)H(5)O* radicals derived from ethanol were
      reevaluated using coupled-cluster theory CCSD(T) calculations, with the aug-cc
      pVnZ (n = D, T, Q) basis sets, that allow the CC energies to be extrapolated at
      the CBS limit. Theoretical results obtained for methanol and two CH(3)O* radicals
      were found to agree within +/-0.5 kcal/mol with the experiment values. A set of
      consistent values was determined for ethanol and its radicals: (a) heats of
      formation (298 K) DeltaHf(C(2)H(5)OH) = -56.4 +/- 0.8 kcal/mol (exptl: -56.21 +/-
      0.12 kcal/mol), DeltaHf(CH(3)C*HOH) = -13.1 +/- 0.8 kcal/mol,
      DeltaHf(C*H(2)CH(2)OH) = -6.2 +/- 0.8 kcal/mol, and DeltaHf(CH(3)CH(2)O*) = -2.7
      +/- 0.8 kcal/mol; (b) bond dissociation energies (BDEs) of ethanol (0 K)
      BDE(CH(3)CHOH-H) = 93.9 +/- 0.8 kcal/mol, BDE(CH(2)CH(2)OH-H) = 100.6 +/- 0.8
      kcal/mol, and BDE(CH(3)CH(2)O-H) = 104.5 +/- 0.8 kcal/mol. The present results
      support the experimental ionization energies and electron affinities of the
      radicals, and appearance energy of (CH(3)CHOH+) cation. Beta-C-C bond scission in
      the ethoxy radical, CH(3)CH2O*, leading to the formation of C*H3 and CH(2)=O, is
      characterized by a C-C bond energy of 9.6 kcal/mol at 0 K, a zero-point-corrected
      energy barrier of E0++ = 17.2 kcal/mol, an activation energy of Ea = 18.0
      kcal/mol and a high-pressure thermal rate coefficient of k(infinity)(298 K) = 3.9
      s(-1), including a tunneling correction. The latter value is in excellent
      agreement with the value of 5.2 s(-1) from the most recent experimental kinetic
      data. Using RRKM theory, we obtain a general rate expression of k(T,p) = 1.26 x
      10(9)p(0.793) exp(-15.5/RT) s(-1) in the temperature range (T) from 198 to 1998 K
      and pressure range (p) from 0.1 to 8360.1 Torr with N2 as the collision partners,
      where k(298 K, 760 Torr) = 2.7 s(-1), without tunneling and k = 3.2 s(-1) with
      the tunneling correction. Evidence is provided that heavy atom tunneling can play
      a role in the rate constant for beta-C-C bond scission in alkoxy radicals.

PMID- 17201395
TI  - Excited-state proton transfer in 7-hydroxy-4-methylcoumarin along a hydrogen
      bonded water wire.
AB  - TDDFT, RI-CC2, and CIS calculations have been performed for the nondissociative
      excited-state proton transfer (ESPT) in the S1 state of 7-hydroxy-4
      methylcoumarin (7H4MC) along a H-bonded water wire of three water molecules
      bridging the proton donor (OH) and the proton acceptor (C[double bond]O) groups
      (7H4MC.(H2O)3). The observed structural reorganization in the water-wire cluster
      is interpreted as a proton-transfer (PT) reaction along the H2O solvent wire. The
      shift of electron density within the organic chromophore 7H4MC due to the optical
      excitation appears to be the driving force for ESPT. All the methods used show
      that the reaction path occurs in the 1pipi* state, and no crossing with a Rydberg
      type 1pisigma* state is found. TDDFT and RI-CC2 calculations predict an exoergic
      reaction of the excited-state enol-to-keto transformation. The S1 potential
      energy curve reveals well-defined Cs minima of enol- and keto-clusters, separated
      by a single barrier with a height of 17-20 kcal/mol. After surmounting this
      barrier, spontaneous PT along the water wire is observed, leading without any
      further barrier to the keto structure. The TDDFT and RI-CC2 methods appear to be
      reliable approaches to describe the energy surfaces of ESPT. The CIS method
      predicts an endoergic ESPT reaction and an energy barrier, which is too high.

PMID- 17201396
TI  - Description of carbo-oxocarbons and assessment of exchange-correlation
      functionals for the DFT description of carbo-mers.
AB  - Mono- and polycyclic valence isomers of carbo-[3]oxocarbon C(9)O(3) and carbo
      [5]oxocarbon C(15)O(5) have been characterized on the singlet spin state
      potential energy surface. By contrast to their geometry, their relative stability
      is highly sensitive to the calculation level. The performance of LDA, GGA, meta
      GGA, and hybrid functionals is compared to that of HF, post-HF, and
      multiconfigurational calculations. The results obtained for C(9)O(3) are compared
      to those obtained for hydrocarbon analogues such as &[3]pericyclyne C9(H2)3 and
      carbo-[3]radialene C9(CH2)3 and are analyzed on the basis of an energy
      decomposition scheme. The respective role of the exchange and correlation
      counterparts of the functional in the discrepancy of the results is discussed.

PMID- 17201397
TI  - Crystal and molecular structure of 4,6-bis(nitroimino)-1,3,5-triazinan-2-one:
      theoretical and X-ray studies.
AB  - This paper provides an overview of recent progress on structural data on the
      title compound. Theoretical work based on quantum mechanical calculations was
      performed to gain some understanding on the heterocyclic tautomerism potentially
      exhibited by the compound. The computational studies encompassed a wide range of
      tautomers/conformers, allowing the determination of the most probable molecular
      structure. In the gas phase, the nitroimine tautomers are computed to be
      substantially more stable than the nitramine tautomers. Among three plausible
      nitroimine forms, special attention was given to 4,6-bis(nitroimino)-1,3,5
      triazinan-2-one, whose crystal structure was unequivocally solved by X-ray
      diffraction. The crystals are orthorhombic, space group Pnma with a = 6.187(2)A,
      b = 13.252(5)A, c = 8.802(4)A, and Z = 4. The structure was solved by direct
      methods and refined to a final R = 0.0326. The molecule has an approximate mirror
      plane relating the two symmetry related halves. The nitroimine groups are
      positioned in a syn-syn conformation. The least-squares (LS) plane of the
      heterocyclic ring and the nitroimine ([double bond]N-NO2) substituent LS plane
      make an angle of 10.05(11) degrees. The crystal structure is held together via
      hydrogen bonds that assemble the molecules in chains running along the b-axis.
      Every H-atom is involved in bifurcated hydrogen bonds.

PMID- 17201398
TI  - Structural and electronic properties of hetero-transition-metal Keggin anions: a
      DFT Study of alpha/beta-[XW12O40]n- (X = CrVI, VV, TiIV, FeIII, CoIII, NiIII,
      CoII, and ZnII) relative stability.
AB  - Density functional theory calculations have been carried out to investigate the
      electronic structures and the alpha/beta relative stability of Keggin-typed
      [XW(12)O(40)]n- anions with transition metal as heteroatom X (X = Cr(VI), V(V),
      Ti(IV), Fe(III), Co(III), Ni(III), Co(II) and Zn(II)). Nice agreement in
      geometries between computation and experiment has been obtained, and the higher
      stability of the alpha isomer over the beta one has been confirmed. Structural
      parameter analysis reveals that the {M(3)O(13)} triads in both alpha and beta
      isomers contract considerably with the increase of the negative anionic charge,
      while the overall size of both isomers shrinks only slightly. Fragment molecular
      orbital analysis shows that except alpha/beta-[TiW(12)O(40)]4-, the electronic
      structures of Keggin anions can be described by the insertion of the e and/or t2
      orbital of XO4n- into the frontier orbitals of W(12)O(36) cage, and this leads to
      the specific redox property, which is different from that of the Keggin anions
      with main-group elements as heteroatoms. Energy decomposition analysis shows that
      the enhanced intrinsic stability of the alpha isomer in Td arrangement of
      W(12)O(36) shell and the larger deformation of the alpha over the beta isomer are
      two dominating factors and contribute oppositely to the alpha/beta relative
      stability.

PMID- 17201399
TI  - Theoretical study on the motion of a La atom inside a C82 cage.
AB  - The motion of a single lanthanum atom inside a C82 (C2v) fullerene cage has been
      investigated by means of the hybrid density functional method (B3LYP). The
      obtained potential energy surface (PES) suggests that the encapsulated La atom
      can oscillate only around the minimum energy potential well, which is apparently
      different from the scenario of a giant bowl-shaped movement at room temperature
      described by Nishibori et al. (Nishibori, E.; Takata, M.; Sakata, M.; Tanaka, H.;
      Hasegawa, M.; Shinohara, H. Chem. Phys. Lett. 2000, 330, 497-502.) Interestingly,
      our calculations show that the La atom may probably undergo a boat-shaped
      movement when the temperature is high enough. In addition, the computed 13C NMR
      spectrum of the C2v [La@C82]- is in an excellent agreement with the experimental
      nuclear magnetic resonance (NMR) spectrum (Tsuchiya, T.; Wakahara, T.; Maeda, Y.;
      Akasaka, T.; Waelchli, M.; Kato, T.; Okubo, H.; Mizorogi, N.; Kobayashi, K.;
      Nagase, S. Anew. Chem. 2005, 117, 3346-3349), which confirms that the isomer of
      La@C82 with the C2v symmetry is the most stable.

PMID- 17201400
TI  - How the shape of the NH2 group depends on the substituent effect and H-bond
      formation in derivatives of aniline.
AB  - The geometry and electronic structure of the amino group in aniline and its
      derivatives are very sensitive to both intramolecular interactions such as
      substituent effects and intermolecular ones such as H-bonding. An analysis of
      experimental geometries retrieved from the CSD base and computational modeling of
      aniline and its derivatives and their H-bonded complexes by use of B3LYP/6
      311+G** and MP2/aug-cc-pVDZ showed that the degree of pyramidalization of the
      amino group depends on H-bonding, which exists in two forms, (i) NH...B (base)
      and (ii) N...HB (Bronsted acid), both of which affect the shape of the NH2 group.
      The effect may be significantly enhanced by a substituent through resonance
      interaction from electron-attracting substituents. The NH...B interactions lead
      to a substantial planarization of the group, whereas N...HB interactions do not.
      The natural bond orbital analysis allowed the authors to show that the changes in
      occupancy of the "lone pair" orbital and in geometry parameters describing
      pyramidalization of the group depend on the substituent constants.

PMID- 17201401
TI  - Designing molecules with optimal properties using the linear combination of
      atomic potentials approach in an AM1 semiempirical framework.
AB  - The linear combination of atomic potentials (LCAP) approach is implemented in the
      AM1 semiempirical framework and is used to design molecular structures with
      optimized properties. The optimization procedure uses property derivative
      information to search molecular space and thus avoid direct enumeration and
      evaluation of each molecule in a library. Two tests are described: the
      optimization of first hyperpolarizabilities of substituted aromatics and the
      optimization of a figure of merit for n-type organic semiconductors.

PMID- 17201402
TI  - Nuclear magnetic resonance chemical shifts and quadrupole couplings for different
      hydrogen-bonding cases occurring in liquid water: a computational study.
AB  - Nuclear magnetic resonance (NMR) parameters are determined theoretically for the
      oxygen and hydrogen/deuterium nuclei of differently hydrogen-bonded water
      molecules in liquid water at 300 K. The parameters are the chemical shift, the
      shielding anisotropy, the asymmetry parameter of shielding, the nuclear
      quadrupole coupling constant, and the asymmetry parameter of the nuclear
      quadrupole coupling. We sample instantaneous configurations from a Car-Parrinello
      molecular dynamics simulation and feed nuclear coordinates into a quantum
      chemical program for the calculation of NMR parameters using density-functional
      theory with the three-parameter hybrid exchange-correlation (B3LYP) functional.
      In the subsequent analysis, molecules are divided into groups according to the
      number of hydrogen bonds they possess, and the full average NMR tensors are
      calculated separately for each group. The classification of the hydrogen-bonding
      cases is performed using a simple distance-based criterion. The analysis reveals
      in detail how the NMR tensors evolve as the environment changes gradually from
      gas to liquid upon increasing the number of hydrogen bonds to the molecule of
      interest. Liquid-state distributions of the instantaneous values of the NMR
      properties show a wide range of values for each hydrogen-bonding species with
      significant overlap between the different cases. Our study shows how local
      changes in the environment, along with classical thermal averaging, affect the
      NMR parameters in liquid water. For example, a broken or alternatively extra
      hydrogen bond induces major changes in the NMR tensors, and the effect is more
      pronounced for hydrogen or deuterium than for oxygen. The data sheds light on the
      usefulness of NMR experiments in investigating the local coordination of liquid
      water.

PMID- 17201404
TI  - Discovery of aminofurazan-azabenzimidazoles as inhibitors of Rho-kinase with high
      kinase selectivity and antihypertensive activity.
AB  - The discovery, proposed binding mode, and optimization of a novel class of Rho
      kinase inhibitors are presented. Appropriate substitution on the 6-position of
      the azabenzimidazole core provided subnanomolar enzyme potency in vitro while
      dramatically improving selectivity over a panel of other kinases. Pharmacokinetic
      data was obtained for the most potent and selective examples and one (6n) has
      been shown to lower blood pressure in a rat model of hypertension.

PMID- 17201406
TI  - Discovery and refinement of a new structural class of potent peptide deformylase
      inhibitors.
AB  - New classes of antibiotics are urgently needed to counter increasing levels of
      pathogen resistance. Peptide deformylase (PDF) was originally selected as a
      specific bacterial target, but a human homologue, the inhibition of which causes
      cell death, was recently discovered. We developed a dual-screening strategy for
      selecting highly effective compounds with low inhibition effect against human
      PDF. We selected a new scaffold in vitro that discriminated between human and
      bacterial PDFs. Analyses of structure-activity relationships identified potent
      antibiotics such as 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (6b) with the
      same mode of action in vivo as previously identified PDF inhibitors but without
      the apoptotic effects of these inhibitors in human cells.

PMID- 17201405
TI  - Development of dihydropyridone indazole amides as selective Rho-kinase
      inhibitors.
AB  - Rho kinase (ROCK1) mediates vascular smooth muscle contraction and is a potential
      target for the treatment of hypertension and related disorders. Indazole amide 3
      was identified as a potent and selective ROCK1 inhibitor but possessed poor oral
      bioavailability. Optimization of this lead resulted in the discovery of a series
      of dihydropyridones, exemplified by 13, with improved pharmacokinetic parameters
      relative to the initial lead. Indazole substitution played a critical role in
      decreasing clearance and improving oral bioavailability.

PMID- 17201408
TI  - Synthesis and biological evaluation of quinoline salicylic acids as P-selectin
      antagonists.
AB  - Leukocyte recruitment of sites of inflammation and tissue injury involves
      leukocyte rolling along the endothelial wall, followed by firm adherence of the
      leukocyte, and finally transmigration of the leukocyte across cell junctions into
      the underlying tissue. The initial rolling step is mediated by the interaction of
      leukocyte glycoproteins containing active moieties such as sialyl Lewisx (sLex)
      with P-selectin expressed on endothelial cells. Consequently, inhibition of this
      interaction by means of a small molecule P-selectin antagonist is an attractive
      strategy for the treatment of inflammatory diseases such as arthritis. High
      throughput screening of the Wyeth chemical library identified the quinoline
      salicylic acid class of compounds (1) as antagonists of P-selectin, with potency
      in in vitro and cell-based assays far superior to that of sLex. Through iterative
      medicinal chemistry, we identified analogues with improved P-selectin activity,
      decreased inhibition of dihydrooratate dehydrogenase, and acceptable CYP
      profiles. Lead compound 36 was efficacious in the rat AIA model of rheumatoid
      arthritis.

PMID- 17201409
TI  - 2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H]quinoline-4-carboxylic
      acid (PSI-697): identification of a clinical candidate from the quinoline
      salicylic acid series of P-selectin antagonists.
AB  - P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial
      cell surface, which subsequently leads to firm adherence and leukocyte
      transmigration through the vessel wall into the surrounding tissues. P-selectin
      is upregulated on the surface of both platelets and endothelium in a variety of
      atherosclerosis-associated conditions. Consequently, inhibition of this
      interaction by means of a small molecule P-selectin antagonist is an attractive
      strategy for the treatment of atherosclerosis. High-throughput screening and
      subsequent analoging had led to the identification of compound 1 as the lead
      candidate. Herein, we report the continuation of this work and the discovery of a
      second-generation series, the tetrahydrobenzoquinoline salicylic acids. These
      compounds have improved pharmacokinetic properties, and a number of them have
      shown oral efficacy in mouse and rat models of atherogenesis and vascular injury.
      The lead 31 (PSI-697), is currently in clinical development for the treatment of
      atherothrombotic vascular events.

PMID- 17201411
TI  - Comparison of shape-matching and docking as virtual screening tools.
AB  - Ligand docking is a widely used approach in virtual screening. In recent years a
      large number of publications have appeared in which docking tools are compared
      and evaluated for their effectiveness in virtual screening against a wide variety
      of protein targets. These studies have shown that the effectiveness of docking in
      virtual screening is highly variable due to a large number of possible
      confounding factors. Another class of method that has shown promise in virtual
      screening is the shape-based, ligand-centric approach. Several direct comparisons
      of docking with the shape-based tool ROCS have been conducted using data sets
      from some of these recent docking publications. The results show that a shape
      based, ligand-centric approach is more consistent than, and often superior to,
      the protein-centric approach taken by docking.

PMID- 17201410
TI  - Structure-activity relationship study of prion inhibition by 2-aminopyridine-3,5
      dicarbonitrile-based compounds: parallel synthesis, bioactivity, and in vitro
      pharmacokinetics.
AB  - 2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as
      mimetics of dominant-negative prion protein mutants and inhibit prion replication
      in cultured cells. Here, we report findings from a comprehensive structure
      activity relationship study of the 6-aminopyridine-3,5-dicarbonitrile scaffold.
      We identify compounds with significantly improved bioactivity (approximately 40
      fold) against replication of the infectious prion isoform (PrPSc) and suitable
      pharmacokinetic profiles to warrant evaluation in animal models of prion disease.

PMID- 17201412
TI  - Discovering potassium channel blockers from synthetic compound database by using
      structure-based virtual screening in conjunction with electrophysiological assay.
AB  - Potassium ion (K+) channels are attractive targets for drug discovery because of
      the essential roles played in biological systems. However, high-throughput
      screening (HTS) cannot be used to screen K+ channel blockers. To overcome this
      disadvantage of HTS, we have developed a virtual screening approach for
      discovering novel blockers of K+ channels. On the basis of a three-dimensional
      model of the eukaryotic K+ channels, molecular docking-based virtual screening
      was employed to search the chemical database MDL Available Chemicals Directory
      (ACD). Compounds were ranked according to their relative binding energy,
      favorable shape complementarity, and potential to form hydrogen bonds with the
      outer mouth of the K+ channel model. Twenty candidate compounds selected from the
      virtual screening were examined using the whole-cell voltage-clamp recording in
      rat dissociated hippocampal neurons. Among them, six compounds (5, 6, 8, 18-20)
      potently blocked both the delayed rectifier (IK) and fast transient K+ currents
      (IA). When applied externally, these six compounds preferentially blocked IK with
      potencies 2- to 500-fold higher than that of tetraethylammonium chloride.
      Intracellular application of the six compounds had no effect on both K+ currents.
      In addition, the interaction models and binding free energy calculations
      demonstrated that hydrophobic interaction and solvent effects play important
      roles in the inhibitory activities of these compounds. The results demonstrated
      that structure-based computer screening strategy could be used to identify novel,
      structurally diverse compounds targeting the pore binding pocket of the outer
      mouth of voltage-gated K+ channels. This study provides an alternative way of
      finding new blockers of voltage-gated K+ channels, while the techniques for high
      throughput screening of K+ channel drugs remain in development.

PMID- 17201414
TI  - Plasma protein binding affinity and its relationship to molecular structure: an
      in-silico analysis.
AB  - In-silico plasma protein binding (PPB) models have been generated on human and
      rat in-house datasets, and on a human dataset sourced from the literature. From
      the results reported herein, it is apparent that models built on datasets
      relevant to the chemotypes under investigation in lead optimization programs will
      perform considerably better in this role than those generated on diverse
      compounds sourced from the literature. The in-house human and rat partial least
      squares regression (PLS) models have cross-validated q2 values of 0.53 and 0.42
      on the training sets, respectively. On the independent test and validation sets,
      they display similar predictive ability, with logK prediction errors of
      approximately 0.5 log units. This compares to approximately 0.25 log units
      variability expected for experiment. Given the considerable interspecies PPB
      differences, the prediction of PPB in one species using measurements in the other
      is no better than a prediction from an in-silico model generated on that species.

PMID- 17201415
TI  - New beta-alanine derivatives are orally available glucagon receptor antagonists.
AB  - A weak human glucagon receptor antagonist with an IC50 of 7 microM was initially
      found by screening of libraries originally targeted to mimic the binding of the
      glucagon-like peptide (GLP-1) hormone to its receptor. Optimization of this hit
      for binding affinity for the glucagon receptor led to ligands with affinity in
      the nanomolar range. In addition to receptor binding, optimization efforts were
      made to stabilize the molecules against fast metabolic turnover. A potent
      antagonist of the human human glucagon receptor was obtained that had 17% oral
      availability in rats with a plasma half-life of 90 min. The major metabolites of
      this lead were identified and used to further optimize this series with respect
      to pharmacokinetic properties. This final optimization led to a potent glucagon
      antagonist that was orally available in rats and dogs and was efficacious in
      lowering blood glucose levels in a diabetic animal model.

PMID- 17201413
TI  - Isofagomine- and 2,5-anhydro-2,5-imino-D-glucitol-based glucocerebrosidase
      pharmacological chaperones for Gaucher disease intervention.
AB  - Gaucher disease, resulting from deficient lysosomal glucocerebrosidase (GC)
      activity, is the most common lysosomal storage disorder. Clinically important GC
      mutant enzymes typically have reduced specific activity and reduced lysosomal
      concentration, the latter due to compromised folding and trafficking. We and
      others have demonstrated that pharmacological chaperones assist variant GC
      folding by binding to the active site, stabilizing the native conformation of GC
      in the neutral pH environment of the endoplasmic reticulum (ER), enabling its
      trafficking from the ER to the Golgi and on to the lysosome. The mutated GC fold
      is generally stable in the lysosome after pharmacological chaperone dissociation,
      owing to the low pH environment for which the fold was evolutionarily optimized
      and the high substrate concentration, enabling GC to hydrolyze glucosylceramide
      to glucose and ceramide. The hypothesis of this study was that we could combine
      GC pharmacological chaperone structure-activity relationships from distinct
      chemical series to afford potent novel chaperones comprising a carbohydrate-like
      substructure that binds in the active site with a hydrophobic substructure that
      binds in a nearby pocket. We combined isofagomine and 2,5-anhydro-2,5-imino-D
      glucitol active site binding substructures with hydrophobic alkyl adamantyl
      amides to afford novel small molecules with enhanced ability to increase GC
      activity in patient-derived fibroblasts. The cellular activity of N370S and G202R
      GC in fibroblasts is increased by 2.5- and 7.2-fold with isofagmine-based
      pharmacological chaperones N-adamantanyl-4-((3R,4R,5R)-3,4-dihydroxy-5
      (hydroxymethyl)piperidin-1-yl)-butanamide (3) and N-adamantanyl-4-((3R,4R,5R)-3,4
      dihydroxy-5-(hydroxymethyl)piperidin-1-yl)pentanamide (4), respectively, the best
      enhancements observed to date.

PMID- 17201416
TI  - Metabolism-based identification of a potent thrombin receptor antagonist.
AB  - The metabolism of our prototypical thrombin receptor antagonist 1, Ki = 2.7 nM,
      was studied and three major metabolites (2, 4, and 5) were found. The structures
      of the metabolites were verified independently by synthesis. Compound 4 was shown
      to be a potent antagonist of the thrombin receptor with a Ki = 11 nM.
      Additionally, compound 4 showed a 3-fold improvement in potency with respect to 1
      in an agonist-induced ex-vivo platelet aggregation assay in cynomolgus monkeys
      after oral administration; this activity was sustained with 60% inhibition
      observed at 24 h post-dose. Compound 4 was highly active in functional assays and
      showed excellent oral bioavailability in rats and monkeys. Compound 4 showed a
      superior rat enzyme induction profile relative to compound 1, allowing it to
      replace compound 1 as a development candidate.

PMID- 17201417
TI  - Polyamine-substituted gadolinium chelates: a new class of intracellular contrast
      agents for magnetic resonance imaging of tumors.
AB  - A new class of intracellular contrast agents (CA) for magnetic resonance imaging
      has been developed, based on Gd(DTPA) with two positively charged amide-linked
      substituents. Uptake of Gd(DTPA) into cultured tumor cell lines (B16 mouse
      melanoma, MH3924A Morris hepatoma) was below the detection limit while CA with
      the melanin-binding pharmacophore 2-(diethylamino)ethylamine reached
      intracellular concentrations of ca. 0.03 fmol/cell (ca. 20 microM) for melanoma
      and 0.02 fmol/cell for hepatoma (24 h at 10 microM CA). With the polyamine
      substituents bis(2-aminoethyl)amine or spermidine, CA uptake increased up to 3
      fold for melanoma (0.083 fmol/cell) and 9-fold for hepatoma (0.18 fmol/cell).
      Uptake of polyamine-substituted CA was reduced by the polyamine transport
      inhibitor benzyl viologen. Molar relaxivities for three Gd-DTPA-polyamine
      complexes were in the range 5.6-6.9 for the free complex in solution and 7.7-23.5
      s-1 mM-1 for Morris hepatoma cell pellets. T1-weighted magnetic resonance imaging
      at 2.35 T of rats with MH3924A tumors showed contrast enhancement in tumor at 1
      and 24 h postinjection of polyamine-substituted CA.

PMID- 17201418
TI  - Discovery and metabolic stabilization of potent and selective 2-amino-N-(adamant
      2-yl) acetamide 11beta-hydroxysteroid dehydrogenase type 1 inhibitors.
AB  - Starting from a rapidly metabolized adamantane 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) inhibitor 22a, a series of E-5-hydroxy-2
      adamantamine inhibitors, exemplified by 22d and (+/-)-22f, was discovered. Many
      of these compounds are potent inhibitors of 11beta-HSD1 and are selective over
      11beta-HSD2 for multiple species (human, mouse, and rat), unlike other reported
      species-selective series. These compounds have good cellular potency and improved
      microsomal stability. Pharmacokinetic profiling in rodents indicated moderate to
      large volumes of distribution, short half-lives, and a pharmacokinetic species
      difference with the greatest exposure measured in rat with 22d. One hour postdose
      liver, adipose, and brain tissue 11beta-HSD1 inhibition was confirmed with (+/-)
      22f in a murine ex vivo assay. Although 5,7-disubstitued-2-adamantamines provided
      greater stability, a single, E-5-position, polar functional group afforded
      inhibitors with the best combination of stability, potency, and selectivity.
      These results indicate that adamantane metabolic stabilization sufficient to
      obtain short-acting, potent, and selective 11beta-HSD1 inhibitors has been
      discovered.

PMID- 17201419
TI  - Partial retro-inverso, retro, and inverso modifications of hydrazide linked
      bifunctional peptides for opioid and cholecystokinin (CCK) receptors.
AB  - Partially modified retro-inverso, retro, and inverso isomers of hydrazide linked
      bifunctional peptides were designed, synthesized, and evaluated for bioactivities
      at delta/mu opioid receptors and CCK-1/CCK-2 receptors. All modifications of the
      CCK pharmacophore moiety affected bioactivities for the CCK-1 and CCK-2 receptors
      (up to 180-fold increase in the binding affinity with higher selectivity) and for
      the delta and mu opioid receptors. The results indicate that the opioid and CCK
      pharmacophores in one molecule interact with each other to induce topographical
      changes for both pharmacophores.

PMID- 17201423
TI  - Electronic properties of neutral dyes in the channels of zeolite L: a combined
      spectroscopic and quantum chemical study.
AB  - Three low molecular weight model compounds for poly(phenylene-ethynylene)s were
      inserted into the channels of zeolite L by using gas phase insertion. The
      absorption and emission spectra in solution and dye/zeolite L are reported. Two
      compounds show emission properties in zeolite L comparable to that in solution.
      In contrast, the bipyridine containing compound shows a red shift toward longer
      excitation wavelengths. Matrix rank analysis of the emission spectra gave three
      contributing species. Quantum chemical calculations provide different
      conformations depending on the Si/Al distribution of the framework and the
      extraframework cations and attached protons.

PMID- 17201422
TI  - Are diamond nanoparticles cytotoxic?
AB  - Finely divided carbon particles, including charcoal, lampblack, and diamond
      particles, have been used for ornamental and official tattoos since ancient
      times. With the recent development in nanoscience and nanotechnology, carbon
      based nanomaterials (e.g., fullerenes, nanotubes, nanodiamonds) attract a great
      deal of interest. Owing to their low chemical reactivity and unique physical
      properties, nanodiamonds could be useful in a variety of biological applications
      such as carriers for drugs, genes, or proteins; novel imaging techniques;
      coatings for implantable materials; and biosensors and biomedical nanorobots.
      Therefore, it is essential to ascertain the possible hazards of nanodiamonds to
      humans and other biological systems. We have, for the first time, assessed the
      cytotoxicity of nanodiamonds ranging in size from 2 to 10 nm. Assays of cell
      viability such as mitochondrial function (MTT) and luminescent ATP production
      showed that nanodiamonds were not toxic to a variety of cell types. Furthermore,
      nanodiamonds did not produce significant reactive oxygen species. Cells can grow
      on nanodiamond-coated substrates without morphological changes compared to
      controls. These results suggest that nanodiamonds could be ideal for many
      biological applications in a diverse range of cell types.

PMID- 17201424
TI  - Ordering in asymmetric block copolymer films by a compressible fluid.
AB  - We examine the morphological structures of asymmetric poly(ethylene oxide)-b
      poly(1,1'-dihydroperflurooctyl methacrylate) (PEO-b-PFOMA) thin films upon
      annealing in a compressible fluid, supercritical CO2 (Sc-CO2). The strong
      affinity between PFOMA and CO2 is found to induce phase segregation when
      annealing PEO-b-PFOMA films at the same temperature as compared with vacuum. In
      vacuum, PEO-b-PFOMA films remain disordered from 80 to 180 degrees C, whereas, in
      Sc-CO2 at 13.9 MPa, an upper order-disorder transition (UODT) between 116 and 145
      degrees C is found. In Sc-CO2, the observed ordered structure is layers of PEO
      spheres embedded in the matrix of PFOMA, followed by a brush layer, in which PEO
      wets the substrate. The swelling isotherms of PFOMA and PEO in CO2 are correlated
      with the Sanchez-Lacombe equation of state (SLEOS) to estimate the interaction
      parameters, XPFOMA-CO2 and XPEO-CO2. The phase segregation (order) induced by CO2
      relative to vacuum at a given temperature is explained in terms of two factors:
      (1) copolymer volume fraction upon dilution with CO2, phi, and (2) the relative
      interaction parameter, DeltaX= XPEO-CO2 - XPFOMA-CO2. The latter factor favors
      order and is dominant at low temperatures over the phi factor, which always
      favors disorder. At high temperatures (above the T(ODT)), the preferential
      swelling of PFOMA by CO2 is less pronounced ( DeltaX decreases), and the
      copolymer is disordered.

PMID- 17201425
TI  - Ab initio investigation of structure and cohesive energy of crystalline urea.
AB  - The structure and cohesive energy of crystalline urea have been investigated at
      the ab initio level of calculation. The performance of different Hamiltonians in
      dealing with a hydrogen-bonded molecular crystal as crystalline urea is assessed.
      Detailed calculations carried out by adopting both HF and some of the most
      popular DFT methods in solid-state chemistry are reported. Local, gradient
      corrected, and hybrid functionals have been adopted: SVWN, PW91, PBE, B3LYP, and
      PBE0. First, a 6-31G(d,p) basis set has been adopted, and then the basis set
      dependence of computed results has been investigated at the B3LYP level. All
      calculations were carried out by using a development version of the periodic ab
      initio code CRYSTAL06, which allows full optimization of lattice parameters and
      atomic coordinates. With the 6-31G(d,p) basis set, structural features are well
      reproduced by hybrid methods and GGA. LDA gives lattice parameters and hydrogen
      bond distances that are too small relative to experiment, while at the HF level
      the opposite trend is observed. Results show that hybrid methods are more
      accurate than HF and both LDA and GGA functionals, with a trend in the computed
      properties similar to that of hydrogen-bonded molecular complexes. When BSSE and
      ZPE are taken into account, all methods, except LDA, give computed cohesive
      energies that are underestimated with respect to the experimental sublimation
      enthalpy. Dispersion energy, not properly taken into account by DFT methods,
      plays a crucial role. Such a deficiency also affects dramatically the computed
      crystalline structure, especially when large basis sets are adopted. We show that
      this is an artifact due to the BSSE. Indeed, with small basis sets the BSSE gives
      an extra-binding that compensates for the missing dispersion forces, thus
      yielding structures in fortuitous agreement with experiment.

PMID- 17201426
TI  - High-spin radical cations of alternating poly(m-p-anilines).
AB  - Three alternating poly(m-p-anilines) have been synthesized via palladium
      catalyzed amination reactions. Polymers were oxidized to radical cations by the
      use of chemical and electrochemical methods. The presence of radical cations was
      manifested by the appearance of two new bands in UV-vis spectra and a strong EPR
      signal. Moreover, EPR spectra at low temperatures confirmed the formation of a
      high-spin state. The magnetization measurements of polymers oxidized to radical
      cations revealed the paramagnetic-type behavior with weak antiferromagnetic
      interactions. Radical cations underwent the degradation processes in the presence
      of air, which led to the decrease of spin concentration.

PMID- 17201427
TI  - Mechanism and kinetics of dehydration of epsomite crystals formed in the presence
      of organic additives.
AB  - The thermal dehydration of epsomite (MgSO4*7H2O) crystals grown in the presence
      and absence of organic additives (phosphonates, carboxylic acids, and polyacrylic
      acid derivatives) was studied by means of thermogravimetry (TG), differential
      scanning calorimetry (DSC), X-ray thermodiffraction (XRTD), and environmental
      scanning electron microscopy (ESEM). In situ XRTD analyses (in air, 30% relative
      humidity) show an -->epsomite hexahydrite (MgSO4*6H2O) transition at 25-38
      degrees C, followed by formation of amorphous phase(s) at T > 43-48 degrees C,
      and MgSO4 crystallization at approximately 300 degrees C. Kinetic parameters
      (E(alpha) and A) were determined for the main dehydration step (25-160 degrees
      C), which corresponds to a MgSO4*7H2O-->MgSO4*H2O transition, by applying two
      isoconversional methods to nonisothermal TG data obtained at different heating
      rates (beta= 1, 3, and 5 K*min-1). In situ, hot-stage ESEM observations of the
      thermal dehydration of epsomite crystals are consistent with the nonisothermal
      kinetic study and, along with XRTD results, allow us to propose a dehydration
      mechanism which includes an early nucleation and growth event, followed by the
      advancement of the reaction interface (3D phase boundary reaction). Both E(alpha)
      and A values increase in the presence of the most effective crystallization
      inhibitors tested. H-bonding between additives and epsomite crystal surfaces is
      consistent with Fourier transform infrared spectroscopy (FTIR) and may account
      for this effect. The increase of E(alpha) values can be related to the excess
      energy required to break additive-water bonds in the reactant. These results are
      likely to further our understanding of the interaction mechanisms between salt
      hydrates and organic additives which act as growth inhibitors/modifiers.

PMID- 17201428
TI  - Conformations of banana-shaped molecules studied by 2H NMR spectroscopy in liquid
      crystalline solvents.
AB  - ClPbis11BB and Pbis11BB, two banana-shaped mesogens differing by a chlorine
      substituent on the central phenyl ring, show a nematic and a B2 phase,
      respectively. To obtain information on the structural features responsible for
      their different mesomorphic behavior, a study of the preferred conformations of
      these mesogens has been performed by NMR spectroscopy in two nematic media (Phase
      IV and ZLI1167), which should mimic the environment of the molecules in their own
      mesophases, avoiding problems of sample alignment by a magnetic field. To this
      aim, 2H NMR experiments have been performed on selectively deuterated isotopomers
      of ClPbis11BB and Pbis11BB and of two parent molecules, ClPbisB and PbisB,
      assumed as models in previous theoretical and experimental conformational
      studies. We found that only a limited number of conformations is compatible with
      experimental data, often very different from those inferred from theoretical
      calculations in vacuo, indicating a strong influence of the liquid crystalline
      environment on molecular conformation. No significant differences between
      chlorinated and non-chlorinated molecules were found, this suggesting that
      chlorine does not change the molecular conformational equilibrium, as previously
      proposed.

PMID- 17201429
TI  - Wormlike micelles of polyoxyethylene alkyl ether mixtures C10E5 + C14E5 and C14E5
      + C14E7: hydrophobic and hydrophilic chain length dependence of the micellar
      characteristics.
AB  - The wormlike micelles formed with the binary mixtures of surfactant
      polyoxyethylene alkyl ethers (CiEj), C10E5 + C14E5 (Mix1) and C14E5 + C14E7
      (Mix2), were characterized by static (SLS) and dynamic light scattering (DLS)
      experiments. The SLS results have been analyzed with the aid of the light
      scattering theory for micelle solutions, thereby yielding the molar mass Mw(c) as
      a function of c along with the cross-sectional diameter d of the micelle. The
      observed Kc/DeltaR0 as a function of c, the mean-square radius of gyration (S2)
      and the hydrodynamic radius RH as functions of Mw have been well described by the
      theories for the wormlike spherocylinder model. It has been found that the
      micellar length increases with increasing concentration c or with raising
      temperature T irrespective of the composition of the surfactant mixtures. The
      length of the Mix1 and Mix2 micelles at fixed c and T steeply increases with
      increasing weight fraction wt of C14E5 in both of the surfactant mixtures,
      implying that the micelles greatly grow in length when the surfactant component
      with longer alkyl group or with shorter oxyethylene group increases in the
      mixture. The results are in line with the findings for the micelles of the single
      surfactant systems where the CiEj micelles grow in length to a greater extent for
      larger i and smaller j. Although the values of d and the spacing s between the
      adjacent surfactant molecules on the micellar surface do not significantly vary
      with composition of the surfactant mixture, the stiffness parameter lambda-1
      remarkably decreases with wt in both Mix1 and Mix2 micelles, indicating that the
      stiffness of the micelle is controlled by the relative strength of the repulsive
      force due to the hydrophilic interactions between oxyethylene groups to the
      attractive one due to the hydrophobic interactions between alkyl groups among the
      surfactant molecules.

PMID- 17201430
TI  - Lateral intermolecular forces between biomembrane lipids in two dimensions: 1,2
      dipalmitin at the heptane/water interface compared with phospholipids.
AB  - The lateral interaction forces between phospholipids in two-dimensional arrays
      are fundamental to understanding membrane biophysics. In previous studies the
      related thermodynamic functions have been measured for spread phospholipid
      monolayers at the oil/water interface over a range of temperatures and densities,
      and the two-dimensional virial coefficients obtained. These coefficients have
      been computed from a model that emphasizes the head group zwitterion
      interactions. In this study we examine the contribution of the diglyceride
      portion of phospholipid molecules to the lateral intermolecular forces.
      Measurements of the heptane/water interfacial tension as a function of the
      concentration of 1,2-dipalmitoyl glycerol (DP) in the heptane were made over a
      range of low surface pressures at 25 degrees C. Infrared measurements on the DP
      solutions show that the solutions are ideal. The results are interpreted to give
      two-dimensional virial coefficients for the adsorbed monolayer. The second virial
      coefficient B2(T) for DP is +0.31 nm2/molecule, in marked contrast to the much
      larger positive values found for the corresponding phospholipids at the same
      interface and temperature, and clearly indicating an attractive component to the
      lateral potentials of mean force between pairs of DP molecules. The contribution
      of the diglyceride moiety to the pair potentials of the phospholipids thus
      appears to be minor but not negligible. The differences in the second virial
      coefficients for DP and the phospholipids are interpreted primarily in terms of
      the orientation of the ester carbonyl dipoles, also drawing on spectroscopic and
      diffraction evidence from related structures.

PMID- 17201431
TI  - Poly(allylamine)-encapsulated water-soluble CdSe nanocrystals.
AB  - Water-soluble CdSe nanocrystal/poly(allylamine) clusters with sizes ranging
      between 50 and 200 nm were prepared using 3-amino-1-propanol as a compatibilizing
      agent. Photoluminescence (PL) quantum yields (QY) up to 20% were achieved in
      water without the need to clad these CdSe nanocrystals (NCs) with higher band gap
      inorganic layers. The polymer-to-nanocrystal ratio plays an important role in the
      internal structure and stability of these polymer/NC clusters, as determined by
      static and dynamic light scattering in conjunction with PL studies. These results
      were modeled by using an effective-mass approximation and perturbation theory on
      the change in dielectric constant of the immediate NC environment. The time
      evolution of the average cluster radius of gyration and hydrodynamic radius
      revealed that a higher polymer-to-NC ratio leads to increased PL stability and
      QY. This is a result of a denser cluster configuration, which affords improved NC
      passivation. Increasing the ionic strength results in greater nanocluster
      compaction and higher PL QYs. Decreasing the pH value below 12 resulted in
      dramatic reduction in PL brightness, despite cluster densification, due to
      partial ionization and dissolution of the amine-based NC surface-capping agents.

PMID- 17201432
TI  - Understanding the effects of surface chemistry on Q: mechanical energy
      dissipation in alkyl-terminated (C1-C18) micromechanical silicon resonators.
AB  - The rate of mechanical energy dissipation in 300-nm-thick, megahertz-range
      micromechanical silicon resonators is sensitive to single monolayer changes in
      surface chemistry. Resonators terminated with a single monolayer of methyl groups
      have significantly higher quality factors (Q's), and thus lower mechanical energy
      dissipation, than comparable resonators terminated with either long-chain alkyl
      monolayers (C2H2n+1, n = 2-18) or monolayers of hydrogen atoms. This effect
      cannot be attributed to mechanical energy dissipation within the alkyl monolayer,
      as a 9-fold increase in alkyl chain length does not lead to an observable
      increase in dissipation. Similarly, this effect is not correlated with the
      chemical structure of the silicon-monolayer interface (e.g., the density of Si-H
      vs Si-C bonds.) Instead, the chemical trends in resonator quality and stability
      are consistent with a dissipation mechanism involving the coupling of long-range
      strain fields to localized, electronically active defects in the monolayer
      coatings.

PMID- 17201433
TI  - Properties of confined and sheared rhodamine B films studied by SFA-FECO
      spectroscopy.
AB  - We have used a surface forces apparatus and multiple beam interferometry to
      measure the absorbance of thin films of rhodamine B in water/ethylene glycol
      solutions while applying and measuring normal and lateral (shear) forces. Both
      normal and shear forces induced changes in the absorption spectra indicating a
      change in molecular alignment, and rhodamine-rhodamine and rhodamine-surface
      interactions. We also measured differences in the absorbance spectra in different
      regions of the contact indicating, as expected, that the stresses are not uniform
      throughout the contact area. We also observed crystallization (solidification)
      parallel to the shearing direction.

PMID- 17201434
TI  - Spontaneous vesicle formation of single chain and double chain cationic
      surfactant mixtures.
AB  - The concentration vs composition diagram of aggregate formation of the
      dodecyltrimethylammonium bromide (DTAB) and didodecyldimethylammonium bromide
      (DDAB) mixture in aqueous solution at rather dilute region was constructed by
      analyzing the surface tension, turbidity, and electrical conductivity data and
      inspected by cryo-TEM images and dynamic light scattering data. Although the
      aqueous solution of DTAB forms only micelles, the transition from monomer to
      small aggregates and then to vesicle was found at 0.1 < X2 <or=1, where X2 is the
      mole fraction of DDAB in the DTAB-DDAB mixture, while vesicle particles were
      formed directly from monomer solution at 0 < X2 < 0.1. Furthermore, the
      transition from vesicle to micelle was found at 0 < X2 < 0.4 at higher
      concentrations. An addition of DTAB to DDAB solution lowered considerably the
      DDAB concentration of the vesicle formation, which is attributable to asymmetric
      distribution of DTAB molecules between inner and outer monolayers of the vesicle
      bilayer. The shape and size of aggregates were obtained from surface tension,
      cryo-TEM, and light scattering data.

PMID- 17201435
TI  - Mechanisms behind the faceting of catanionic vesicles by polycations: chain
      crystallization and segregation.
AB  - Vesicles composed of an anionic and a cationic surfactant, with a net negative
      charge, associate strongly with a hydrophobically modified polycation (LM200) and
      with an unmodified polycation with higher charge density (JR400), forming
      viscoelastic gel-like structures. Calorimetric results show that in these gels,
      LM200 induces a rise of the chain melting temperature (Tm) of the vesicles,
      whereas JR400 has the opposite effect. For both polymer-vesicle systems, the
      shear viscosity exhibits an inflection point at Tm, and for the LM200 system the
      measured relaxation times are significantly higher below Tm. The neat vesicles
      and the polycation-bound vesicles have a polygonal-like faceted shape when the
      surfactant chains in the bilayer are crystallized, as probed by cryo-transmission
      electron microscopy. Above Tm, the neat and the LM200-bound vesicles regain a
      spheroidal shape, whereas those in the JR400 system remain with a deformed
      faceted shape even above Tm. These shape changes are interpreted in terms of
      different mechanisms for the polymer-vesicle interaction, which seem to be highly
      dependent on polymer architecture, namely charge density and hydrophobic
      modification. A crystallization-segregation mechanism is proposed for the LM200
      vesicle system, while, for the JR400-vesicle one, charge polarization-lateral
      segregation effects induced by the polycation in the catanionic bilayer are
      envisaged.

PMID- 17201436
TI  - Fluorescence, circular dichroism, light scattering, and microscopic
      characterization of vesicles of sodium salts of three N-acyl peptides.
AB  - Aggregation behavior of three N-acyl peptide surfactants, sodium N-(4-n
      dodecyloxybenzoyl)-L-alyl-L-valinate (SDBAV), L-valyl-L-alaninate (SDBVA), and L
      valyl-L-valinate (SDBVV), were investigated. The amphiphiles have very low
      critical aggregation concentration (cac). Fluorescence anisotropy studies using
      1,6-diphenyl-1,3,5-hexatriene (DPH) as a fluorescent probe indicated formation of
      bilayer aggregates in dilute solution. Transmission electron micrographs showed
      the existence of large vesicles in dilute solution. Circular dichroism spectra
      suggested formation of helical aggregates. The vesicle formation was found to be
      more favored at neutral pH. Dynamic light scattering was used to measure
      hydrodynamic radius of the vesicles. The microviscosity of the vesicles formed by
      the amphiphiles was determined by use of fluorescence anisotropy and the lifetime
      of the DPH probe. The vesicles formed by the surfactants are stable at
      temperatures above body temperature and for a long period of time. Fluorescence
      probe studies, however, indicated transformation of vesicles to rod-like micelles
      at surfactant concentrations much higher than the cac value. Addition of sodium
      chloride also transformed the vesicles to rod-like micelles.

PMID- 17201437
TI  - Solvatochromic studies of ionic liquid/organic mixtures.
AB  - Room-temperature ionic liquids (ILs) have potential for many different
      applications, including catalysis and synthesis. Organics are often present
      during IL applications; therefore, a more fundamental understanding of the
      interactions between IL and organics is necessary. A systematic study of the
      effects of organic cosolvents, cations, and anions on the solvent strength of
      IL/organic mixtures will allow for a greater understanding and potential for
      tuning of ILs for specific purposes. Solvent strength is commonly quantified
      using spectroscopic probes. We report the solvent strength of IL/organic mixtures
      using Reichardt's dyes 30 and 33, Kamlet-Taft parameters, and phenol blue. The
      results show that the polarity of ILs is largely unaffected by the organic
      cosolvent; that is, the probes are preferentially solvated by the ILs. However,
      more specific solvation forces, such as hydrogen bonding, can be influenced
      indirectly by the strength of the anion/cation interaction, giving
      counterintuitive results.

PMID- 17201438
TI  - Microscopic description of elementary growth processes and classification of
      structural defects in pentacene thin films.
AB  - Elementary growth processes such as kink initiation, adding a molecule to a kink,
      and adding a molecule between two neighboring kinks and between two grains are
      theoretically studied in pentacene films by adding one molecule at a time to a
      predefined aggregate. For each molecule, the potential energy surface is
      calculated using the MM3 molecular mechanics force field, which allowed one to
      identify useful parameters like the energy barrier for diffusion and the energy
      to create kinks, as well as defect configurations. Depending on the properties of
      the potential energy surface and the resulting growth-condition-dependent
      probabilities of initiating defect configurations in the film, three types of
      pentacene defects are identified: a thermally activated defect, an intrinsic
      defect, and a kinetic defect. Upon film growth, most defects relax into the ideal
      crystal configuration. Bulk defects that resist relaxation have densities lower
      than 10(16) defects/cm3 at typical growth conditions. Grain boundary defects, on
      the other hand, are very stable. Moreover, interstitial molecules at grain
      boundaries are identified as a source of compressive stress.

PMID- 17201440
TI  - Coherent versus uncorrelated nanoscale heterogeneities in L1(0) solid solutions
      and their signatures from local and extended probes.
AB  - The structural properties of the phase coexistence of chemically ordered L1(0)
      and chemically disordered structures within binary alloys are investigated, using
      the NiMn system as an example. Theoretical and numerical predictions of the
      signatures that one might expect in data from local and extended probes are
      presented in an attempt to explain the presence of antiferromagnetism in NiMn
      when no L1(0) signatures appear in diffraction data. Two scenarios are
      considered. In the first scenario, the tetragonal L1(0) structure and fcc
      chemically disordered structure are distributed evenly into uncorrelated domains
      of specified average diameter. The diffraction limit, below which the two
      structures can only be distinguished using a local probe, is quantified with
      respect to the domain diameter by applying straightforward diffraction analysis.
      In the second scenario, domains with chemical ordering oriented in different
      directions are required to maintain their atomic coherence with each other. A
      numerical treatment is used to illustrate the long-range strain that results from
      elastic energy considerations, and the effects on the structure factor (extended
      probe) and pair distribution function (local probe) are investigated.

PMID- 17201439
TI  - Stability of different zinc(II)-diamine complexes in aqueous solution with
      respect to structure and dynamics: a QM/MM MD study.
AB  - In the context of our detailed study of the chemical behavior of aquo- and ammine
      Zn(II) complexes, ab initio quantum mechanical/molecular mechanical (QM/MM)
      molecular dynamics (MD) simulations were performed at the Hartree-Fock (HF) level
      for the zinc(II)-diamine complexes in aqueous solution. The initial structures of
      cis and trans isomers of the tetraaquodiamminezinc(II) complex were found to
      transform into the triaquodiamminezinc(II) complex by releasing one water ligand
      after approximately 6 and approximately 22 ps of simulation time, respectively.
      The structural and dynamical properties of these three zinc complexes, i.e., cis
      [Zn(NH3)2(H2O)4]2+, trans-[Zn(NH3)2(H2O)4]2+, and [Zn(NH3)2(H2O)3]2+, were
      analyzed in terms of radial distribution functions (RDF), coordination number
      distributions (CND), angular distribution functions (ADF), tilt and theta angle
      distributions, ligands' mean residence times (MRTs), and ion-ligand stretching
      frequencies. One considerably elongated Zn-O bond of 2.43 A was observed in the
      case of the cis isomer for one of the water ligands located in the trans position
      to an ammonia ligand. In the trans isomer the average Zn-O bond length was
      observed to be 2.23 A, while in the triaquodiamminezinc(II) complex two distinct
      Zn-O bonds, namely 2.12 A for the ligands in the trigonal plane and 2.26 A for
      axial water molecules, were observed. As both of the octahedral isomers are
      transformed into the pentacoordinated structure within the picosecond range, they
      might be regarded as "metastable species or intermediates", while the
      triaquodiamminezinc(II) complex is the most stable species of the zinc(II)
      diamine complex in aqueous solution.

PMID- 17201441
TI  - Computational approach to nuclear magnetic resonance in 1-Alkyl-3
      methylimidazolium ionic liquids.
AB  - A quantum-chemical computational approach to accurately predict the nuclear
      magnetic resonance (NMR) properties of 1-alkyl-3-methylimidazolium ionic liquids
      has been performed by the gauge-including atomic orbitals method at the B3LYP/6
      31++G** level using different simulated ionic liquid environments. The first
      molecular model chosen to describe the ionic liquid system includes the gas-phase
      optimized structures of ion pairs and separated ions of a series of imidazolium
      salts containing methyl, butyl, and octyl substituents and PF6-, BF4-, and Br-
      anions. In addition, a continuum polarizable model of solvation has been applied
      to predict the effects of the medium polarity on the molecular properties of 1,3
      dimethylimidazolium hexafluorophosphate (MmimPF6). Furthermore, the specific
      acidic and basic solute-solvent interactions have been simulated by a discrete
      solvation model based on molecular clusters formed by MmimPF6 species and a
      discrete number of water molecules. The computational prediction of the NMR
      spectra allows a consistent interpretation of the dispersed experimental evidence
      in the literature. The following are main contributions of this work: (a)
      Theoretical results state the presence of a chemical equilibrium between ion-pair
      aggregates and solvent-separated counterions of 1-alkyl-3-methylimidazolium salts
      which is tuned by the solvent environment; thus, strong specific (acidic and
      basic) and nonspecific (polarity and polarizability) solvent interactions are
      predicted favoring the dissociated ionic species. (b) The calculated 1H and 13C
      NMR properties of these ionic liquids are revealed as highly dependent on the
      nature of solute-solvent interactions. Thus, the chemical shift of the hydrogen
      atom in position two of the imidazolium ring is deviated to high values by the
      specific interactions with water molecules, whereas nonspecific interaction with
      water (as a solvent) affects, in the opposite direction, this 1H NMR parameter.
      (c) Last, current calculations support the presence of hydrogen bonding between
      counterions, suggesting the importance of this interaction in the properties of
      the solvent in the 1-alkyl-3-methylimidazolium ionic liquids.

PMID- 17201442
TI  - Standard thermodynamic properties of H3PO4(aq) over a wide range of temperatures
      and pressures.
AB  - The densities and heat capacities of solutions of phosphoric acid, 0.05 to 1 mol
      kg-1, were measured using flow vibrating tube densitometry and differential
      Picker-type calorimetry at temperatures up to 623 K and at pressures up to 28
      MPa. The standard molar volumes and heat capacities of molecular H3PO4(aq) were
      obtained, via the apparent molar properties corrected for partial dissociation,
      by extrapolation to infinite dilution. The data on standard derivative properties
      were correlated simultaneously with the dissociation constants of phosphoric acid
      from the literature using the theoretically founded SOCW model. This made it
      possible to describe the standard thermodynamic properties, particularly the
      standard chemical potential, of both molecular and ionized phosphoric acid at
      temperatures up to at least 623 K and at pressures up to 200 MPa. This
      representation allows one to easily calculate the first-degree dissociation
      constant of H3PO4(aq). The performance of the SOCW model was compared with the
      other approaches for calculating the high-temperature dissociation constant of
      the phosphoric acid. Using the standard derivative properties, sensitively
      reflecting the interactions between the solute and the solvent, the high
      temperature behavior of H3PO4(aq) is compared with that of other weak acids.

PMID- 17201443
TI  - Molecular and thermal diffusion coefficients of alkane-alkane and alkane-aromatic
      binary mixtures: effect of shape and size of molecules.
AB  - New molecular and thermal diffusion coefficients of binary mixtures of normal
      decane-normal alkanes and methylnaphthalene-normal alkanes are measured at
      atmospheric pressure and T = 25 degrees C. The normal alkanes used in this work
      include nC5-nC20. Thermal diffusion coefficients were measured in a
      thermogravitational column. Molecular diffusion coefficients were measured using
      an open-ended capillary tube technique. Results show a significant effect of
      molecular shape and size on thermal and molecular diffusion coefficients.
      Molecular diffusion coefficients show a monotonic behavior in both aromatic
      normal alkane and normal decane-normal alkane mixtures. Thermal diffusion
      coefficients reveal a nonmonotonic trend with molecular size in the normal decane
      normal alkane mixtures. This is the first report of the nonmonotonic behavior in
      the literature. The data presented in this paper provide an accurate self
      molecular diffusion coefficient for nC10 from binary data.

PMID- 17201444
TI  - Local ordering in liquids: solvent effects on the hyperfine couplings of the
      cyclohexadienyl radical.
AB  - Ordering of solvent molecules in the vicinity of a dipolar free radical affects
      its hyperfine coupling constants (hfcs). Specifically, it is demonstrated how the
      variation of the experimental methylene proton and muon hfcs of the muoniated
      cyclohexadienyl radical in several solvents and solvent mixtures of varying
      polarity can be accounted for by a dipole-dipole reaction field model that is
      based on the model of Reddoch and Konishi (J. Chem. Phys. 1979, 70, 2121) which
      was developed to explain the solvent dependence of the 14N hfc in the di-tert
      butyl-nitroxide radical. Ab initio calculations were carried out with the
      cyclohexadienyl radical in an electric field to model the electric field arising
      from the electric dipole moments of the surrounding solvent molecules. An
      extension of the model that includes the dipole-quadrupole interaction can
      account for the larger hfc in benzene compared with that in octadecane, and it is
      predicted that the hfc will be proportional to the concentration of quadrupole
      moments to the 4/3 power. The influence of hydrogen bonding between the radicals'
      pi electrons and the OH groups of the solvent on the hfcs is also discussed.
      Comparison with gas-phase data permits a separation of vibrational effects and
      reveals that approximately 28% of the temperature dependence in water is due to
      increasing solvent disorder.

PMID- 17201445
TI  - Structural and dynamic properties of concentrated alkali halide solutions: a
      molecular dynamics simulation study.
AB  - The physicochemical properties of alkali halide solutions have long been
      attributed to the collective interactions between ions and water molecules in the
      solution, yet the structure of water in these systems and its effect on the
      equilibrium and dynamic properties of these systems are not clearly understood.
      Here, we present a systematic view of water structure in concentrated alkali
      halide solutions using molecular dynamics simulations. The results of the
      simulations show that the size of univalent ions in the solution has a
      significant effect on the dynamics of ions and other transport properties such as
      the viscosity that are correlated with the structural properties of water in
      aqueous ionic solution. Small cations (e.g., Li+) form electrostatically
      stabilized hydrophilic hydration shells that are different from the hydration
      shells of large ions (e.g., Cs+) which behave more like neutral hydrophobic
      particles, encapsulated by hydrogen-bonded hydration cages. The properties of
      solutions with different types of ion solvation change in different ways as the
      ion concentration increases. Examples of this are the diffusion coefficients of
      the ions and the viscosities of solutions. In this paper we use molecular
      dynamics (MD) simulations to study the changes in the equilibrium and transport
      properties of LiCl, RbCl, and CsI solutions at concentrations from 0.22 to 3.97
      M.

PMID- 17201446
TI  - Energetics and dynamics in MbCN: CN--vibrational relaxation from molecular
      dynamics simulations.
AB  - The dynamics of the cyanide anion bound to sperm-whale myoglobin is investigated
      using atomistic simulations. With density-functional theory, a 2D potential
      energy surface for the cyanide-heme complex is calculated. Two deep minima with a
      stabilization energy of approximately 50 kcal/mol corresponding to two different
      binding orientations (Fe-CN and Fe-NC) of the ligand are found. The Fe-CN
      conformation is favored over Fe-NC by several kcal/mol. Mixed quantum
      mechanics/molecular mechanics calculations show that the binding orientation
      affects the bond strength of the ligand, with a significantly different bond
      length and a 25 cm-1 shift in the fundamental CN-frequency. For the molecular
      dynamics (MD) simulations, a 3-center fluctuating charge model for the Fe-CN unit
      is developed that captures polarization and ligand-metal charge transfer.
      Stability arguments based on the energetics around the active site and the CN-
      frequency shifts suggest that the Fe-CN conformation with epsilon-protonation of
      His epsilon 64 are most likely, which is in agreement with experiment. Both
      equilibrium and nonequilibrium MD simulations are carried out to investigate the
      relaxation time scale and possible relaxation pathways in bound MbCN. The
      nonequilibrium MD simulations with a vibrationally excited ligand reveal that
      vibrational relaxation takes place on a time scale of hundreds of picoseconds
      within the active site. This finding supports the hypothesis that the
      experimentally observed relaxation rate (3.6 ps) reflects the repopulation of the
      electronic ground state.

PMID- 17201447
TI  - Liquid-structure forces and electrostatic modulation of biomolecular interactions
      in solution.
AB  - Molecular interactions in solution are controlled by the bulk medium and by the
      forces originating in the structured region of the solvent close to the solutes.
      In this paper, a model of electrostatic and liquid-structure forces for dynamics
      simulations of biomolecules is presented. The model introduces information on the
      microscopic nature of the liquid in the vicinity of polar and charged groups and
      the associated non-pairwise character of the forces, thus improving upon
      conventional continuum representations. The solvent is treated as a polar and
      polarizable medium, with dielectric properties described by an inhomogeneous
      version of the Onsager theory. This treatment leads to an effective position
      dependent dielectric permittivity that incorporates saturation effects of the
      electric field and the spatial variation of the liquid density. The non-pairwise
      additivity of the liquid-structure forces is represented by centers of force
      located at specific points in the liquid phase. These out-of-the-solute centers
      are positioned at the peaks of liquid density and exert local, external forces on
      the atoms of the solute. The density is calculated from a barometric law, using a
      Lennard-Jones-type solute-liquid effective interaction potential. The conceptual
      aspects of the model and its exact numerical solutions are discussed for single
      alkali and halide ions and for ion-pair interactions. The practical aspects of
      the model and the simplifications introduced for efficient computation of forces
      in molecular solutes are discussed in the context of polar and charged amino acid
      dimers. The model reproduces the contact and solvent-separated minima and the
      desolvation barriers of intermolecular potentials of mean force of amino acid
      dimers, as observed in atomistic dynamics simulations. Possible refinements based
      on an improved treatment of molecular correlations are discussed.

PMID- 17201448
TI  - Cation-pi interactions stabilize the structure of the antimicrobial peptide
      indolicidin near membranes: molecular dynamics simulations.
AB  - We implemented molecular dynamics simulations of the 13-residue antimicrobial
      peptide indolicidin (ILPWKWPWWPWRR-NH2) in dodecylphosphocholine (DPC) and sodium
      dodecyl sulfate (SDS) micelles. In DPC, a persistent cation-pi interaction
      between TRP11 and ARG13 defined the structure of the peptide near the interface.
      A transient cation-pi interaction was also observed between TRP4 and the choline
      group on DPC lipids. We also implemented simulation of a mutant of indolicidin in
      the DPC micelle where TRP11 was replaced by ALA11. As a result of the mutation,
      the boat-shaped conformation is lost and the structure becomes significantly less
      defined. On the basis of this evidence, we argue that cation-pi interactions
      determine the experimentally measured, well-defined boat-shaped structure of
      indolicidin. In SDS, the lack of such interactions and the electrostatic binding
      of the terminal arginine residues to the sulfate groups leads to an extended
      peptide structure. To the best of our knowledge, this is the first time that a
      cation-pi interaction between peptide side chains has been shown to stabilize the
      structure of a small antimicrobial peptide. The simulations are in excellent
      agreement with available experimental measurements: the backbone of the peptide
      is more ordered in DPC than in SDS; the tryptophan side chains pack against the
      backbone in DPC and point away from the backbone in SDS; the rms fluctuation of
      the peptide backbone and peptide side chains is greater in SDS than in DPC; and
      the peptide backbone order parameters are higher in DPC than in SDS.

PMID- 17201449
TI  - Protein interactions studied by SAXS: effect of ionic strength and protein
      concentration for BSA in aqueous solutions.
AB  - We have studied a series of samples of bovine serum albumin (BSA) solutions with
      protein concentration, c, ranging from 2 to 500 mg/mL and ionic strength, I, from
      0 to 2 M by small-angle X-ray scattering (SAXS). The scattering intensity
      distribution was compared to simulations using an oblate ellipsoid form factor
      with radii of 17 x 42 x 42 A, combined with either a screened Coulomb, repulsive
      structure factor, SSC(q), or an attractive square-well structure factor, SSW(q).
      At pH = 7, BSA is negatively charged. At low ionic strength, I < 0.3 M, the total
      interaction exhibits a decrease of the repulsive interaction when compared to the
      salt-free solution, as the net surface charge is screened, and the data can be
      fitted by assuming an ellipsoid form factor and screened Coulomb interaction. At
      moderate ionic strength (0.3-0.5 M), the interaction is rather weak, and a hard
      sphere structure factor has been used to simulate the data with a higher volume
      fraction. Upon further increase of the ionic strength (I >or= 1.0 M), the overall
      interaction potential was dominated by an additional attractive potential, and
      the data could be successfully fitted by an ellipsoid form factor and a square
      well potential model. The fit parameters, well depth and well width, indicate
      that the attractive potential caused by a high salt concentration is weak and
      long-ranged. Although the long-range, attractive potential dominated the protein
      interaction, no gelation or precipitation was observed in any of the samples.
      This is explained by the increase of a short-range, repulsive interaction between
      protein molecules by forming a hydration layer with increasing salt
      concentration. The competition between long-range, attractive and short-range,
      repulsive interactions accounted for the stability of concentrated BSA solution
      at high ionic strength.

PMID- 17201451
TI  - Red antenna states of photosystem I from cyanobacteria Synechocystis PCC 6803 and
      Thermosynechococcus elongatus: single-complex spectroscopy and spectral hole
      burning study.
AB  - Hole-burning and single photosynthetic complex spectroscopy were used to study
      the excitonic structure and excitation energy-transfer processes of
      cyanobacterial trimeric Photosystem I (PS I) complexes from Synechocystis PCC
      6803 and Thermosynechococcus elongatus at low temperatures. It was shown that
      individual PS I complexes of Synechocystis PCC 6803 (which have two red antenna
      states, i.e., C706 and C714) reveal only a broad structureless fluorescence band
      with a maximum near 720 nm, indicating strong electron-phonon coupling for the
      lowest energy C714 red state. The absence of zero-phonon lines (ZPLs) belonging
      to the C706 red state in the emission spectra of individual PS I complexes from
      Synechocystis PCC 6803 suggests that the C706 and C714 red antenna states of
      Synechocystis PCC 6803 are connected by efficient energy transfer with a
      characteristic transfer time of approximately 5 ps. This finding is in agreement
      with spectral hole-burning data obtained for bulk samples of Synechocystis PCC
      6803. The importance of comparing the results of ensemble (spectral hole burning)
      and single-complex measurements was demonstrated. The presence of narrow ZPLs
      near 710 nm in addition to the broad fluorescence band at approximately 730 nm in
      Thermosynechococcus elongatus (Jelezko et al. J. Phys. Chem. B 2000, 104, 8093
      8096) has been confirmed. We also demonstrate that high-quality samples obtained
      by dissolving crystals of PS I of Thermosynechococcus elongatus exhibit stronger
      absorption in the red antenna region than any samples studied so far by us and
      other groups.

PMID- 17201450
TI  - Modification and optimization of the united-residue (UNRES) potential energy
      function for canonical simulations. I. Temperature dependence of the effective
      energy function and tests of the optimization method with single training
      proteins.
AB  - We report the modification and parametrization of the united-residue (UNRES)
      force field for energy-based protein structure prediction and protein folding
      simulations. We tested the approach on three training proteins separately: 1E0L
      (beta), 1GAB (alpha), and 1E0G (alpha + beta). Heretofore, the UNRES force field
      had been designed and parametrized to locate native-like structures of proteins
      as global minima of their effective potential energy surfaces, which largely
      neglected the conformational entropy because decoys composed of only lowest
      energy conformations were used to optimize the force field. Recently, we
      developed a mesoscopic dynamics procedure for UNRES and applied it with success
      to simulate protein folding pathways. However, the force field turned out to be
      largely biased toward -helical structures in canonical simulations because the
      conformational entropy had been neglected in the parametrization. We applied the
      hierarchical optimization method, developed in our earlier work, to optimize the
      force field; in this method, the conformational space of a training protein is
      divided into levels, each corresponding to a certain degree of native-likeness.
      The levels are ordered according to increasing native-likeness; level 0
      corresponds to structures with no native-like elements, and the highest level
      corresponds to the fully native-like structures. The aim of optimization is to
      achieve the order of the free energies of levels, decreasing as their native
      likeness increases. The procedure is iterative, and decoys of the training
      protein(s) generated with the energy function parameters of the preceding
      iteration are used to optimize the force field in a current iteration. We applied
      the multiplexing replica-exchange molecular dynamics (MREMD) method, recently
      implemented in UNRES, to generate decoys; with this modification, conformational
      entropy is taken into account. Moreover, we optimized the free-energy gaps
      between levels at temperatures corresponding to a predominance of folded or
      unfolded structures, as well as to structures at the putative folding-transition
      temperature, changing the sign of the gaps at the transition temperature. This
      enabled us to obtain force fields characterized by a single peak in the heat
      capacity at the transition temperature. Furthermore, we introduced temperature
      dependence to the UNRES force field; this is consistent with the fact that it is
      a free-energy and not a potential energy function. beta

PMID- 17201453
TI  - Binding geometry and photophysical properties of DNA-threading binuclear
      ruthenium complexes.
AB  - The DNA binding conformation and the photophysical properties of the semiflexible
      binuclear ruthenium complex [micro-bidppz(phen)4Ru2]4+ (2) were studied with
      optical spectroscopy and compared to the rigid, planar homologue in syn
      conformation [micro-dtpf(phen)4Ru2]4+ (3) and the parent "light-switch" complex
      [Ru(phen)2dppz]2+ (1). Comparison of calculated and observed absorption bands of
      the bridging ligand, bidppz, confirm earlier suggestions that 2 is significantly
      nonplanar, both free in solution and when intercalated into poly(dAdT)2, but the
      conclusion that the intercalated conformation is an anti rotamer is not
      substantiated by comparison of linear and circular dichroism spectra of 2 and 3.
      The behavior of the emission quantum yield as a function of temperature is
      similar for the two binuclear complexes 2 and 3 in different protic solvents, and
      a quantitative analysis suggests that, in solution, the solvent is more strongly
      hydrogen bonded to the excited state of 2 than to 1. However, the observation
      that for 2 the radiative rate constant increases to a value similar to 1 upon
      intercalation into DNA suggests that the difference between 1 and 2 in accepting
      hydrogen bonds is less pronounced when intercalated.

PMID- 17201452
TI  - Molecular dynamics with the United-residue force field: ab initio folding
      simulations of multichain proteins.
AB  - The implementation of molecular dynamics with the united-residue (UNRES) force
      field is extended to treat multichain proteins. Constant temperature was
      maintained in the simulations with Berendsen or Langevin thermostats. The method
      was tested on three alpha-helical proteins (1G6U and GCN4-p1, each with two
      chains, and 1C94, with four chains). Simulations were carried out for both the
      isolated single chains and the multichain complexes. The proteins were folded by
      starting from the extended conformation with random initial velocities and with
      the chains parallel to each other. No symmetry constraints or structure
      information were included for the single chains or the multichain complexes. In
      the case of single-chain simulations, a high percentage of the trajectories (100%
      for 1G6U, 90% for GCN4-p1, and 80% for 1C94) converged to nativelike structures
      (assumed as the experimental structure of a monomer in the multichain complex),
      showing that, for the proteins studied in this work with the UNRES force field,
      the interactions between chains are not critical for stabilization of the
      individual chains. In the case of multichain simulations, the native structures
      of the 1G6U and GCN4-p1 complexes, but not that of 1C94, are predicted
      successfully. The association of the subunits does not follow a unique mechanism;
      the monomers were observed to fold both before and simultaneously with their
      association.

PMID- 17201454
TI  - Comment on "kinetics of solute adsorption at solid/solution interfaces: a
      theoretical development of the empirical pseudo-first and pseudo-second order
      kinetic rate equations, based on applying the statistical rate theory of
      interfacial transport".

PMID- 17201456
TI  - Pharmacokinetic interactions with thiazolidinediones.
AB  - Type 2 diabetes mellitus is a complex disease combining defects in insulin
      secretion and insulin action. New compounds called thiazolidinediones or
      glitazones have been developed for reducing insulin resistance. After the
      withdrawal of troglitazone because of liver toxicity, two compounds are currently
      used in clinical practice, rosiglitazone and pioglitazone. These compounds are
      generally used in combination with other pharmacological agents. Because they are
      metabolised via cytochrome P450 (CYP), glitazones are exposed to numerous
      pharmacokinetic interactions. CYP2C8 and CYP3A4 are the main isoenzymes
      catalysing biotransformation of pioglitazone (as with troglitazone), whereas
      rosiglitazone is metabolised by CYP2C9 and CYP2C8. For both rosiglitazone and
      pioglitazone, the most relevant interactions have been described in healthy
      volunteers with rifampicin (rifampin), which results in a significant decrease of
      area under the plasma concentration-time curve [AUC] (54-65% for rosiglitazone,
      p<0.001; 54% for pioglitazone, p<0.001), and with gemfibrozil, which results in a
      significant increase of AUC (130% for rosiglitazone, p<0.001; 220-240% for
      pioglitazone, p<0.001). The relevance of such drug-drug interactions in patients
      with type 2 diabetes remains to be evaluated. However, in the absence of clinical
      data, it is prudent to reduce the dosage of each glitazone by half in patients
      treated with gemfibrozil. Conversely, rosiglitazone and pioglitazone do not seem
      to significantly affect the pharmacokinetics of other compounds. Although some
      food components have also been shown to potentially interfere with drugs
      metabolised with the CYP system, no published study deals specifically with these
      possible CYP-mediated food-drug interactions with glitazones.

PMID- 17201458
TI  - Sequential updating of a new dynamic pharmacokinetic model for caffeine in
      premature neonates.
AB  - BACKGROUND AND OBJECTIVE: Caffeine treatment is widely used in nursing care to
      reduce the risk of apnoea in premature neonates. To check the therapeutic
      efficacy of the treatment against apnoea, caffeine concentration in blood is an
      important indicator. The present study was aimed at building a pharmacokinetic
      model as a basis for a medical decision support tool. METHODS: In the proposed
      model, time dependence of physiological parameters is introduced to describe
      rapid growth of neonates. To take into account the large variability in the
      population, the pharmacokinetic model is embedded in a population structure. The
      whole model is inferred within a Bayesian framework. To update caffeine
      concentration predictions as data of an incoming patient are collected, we
      propose a fast method that can be used in a medical context. This involves the
      sequential updating of model parameters (at individual and population levels) via
      a stochastic particle algorithm. RESULTS: Our model provides better predictions
      than the ones obtained with models previously published. We show, through an
      example, that sequential updating improves predictions of caffeine concentration
      in blood (reduce bias and length of credibility intervals). The update of the
      pharmacokinetic model using body mass and caffeine concentration data is studied.
      It shows how informative caffeine concentration data are in contrast to body mass
      data. CONCLUSION: This study provides the methodological basis to predict
      caffeine concentration in blood, after a given treatment if data are collected on
      the treated neonate.

PMID- 17201459
TI  - Clinical scoring system for the prediction of target site penetration of
      antimicrobials in patients with sepsis.
AB  - BACKGROUND AND OBJECTIVES: The present study investigated the usefulness of
      routinely employed scoring systems in predicting tissue penetration of
      antimicrobials. In addition, a novel, easy to use scoring system was designed for
      the estimation of tissue penetration of antimicrobials in patients with sepsis.
      METHODS: Tissue pharmacokinetics were assessed in skeletal muscle and
      subcutaneous adipose tissue by use of the microdialysis technique in 34 patients
      with sepsis. Tissue penetration of antimicrobials was retrospectively determined
      by the ratios of the area under the concentration-time curves (AUC) in soft
      tissues (AUCtissue) to the AUC in plasma (AUCplasma). Mortality and sepsis scores
      currently used in intensive care were consecutively calculated and correlated
      with the AUCtissue:AUCplasma ratio. Single laboratory and clinical parameters
      showing the highest correlation with tissue penetration were identified and used
      in the novel Tissue Penetration Prediction Score (TPPS). RESULTS: The currently
      used scoring systems Simplified Acute Physiology Scores 3 (r=-0.33, p=0.006),
      Acute Physiology and Chronic Health Evaluation III (r=-0.27, p=0.03) and Sepsis
      Related (or Sequential) Organ Failure Assessment (r=-0.32, p=0.01) showed
      significant overall correlations with tissue penetration. However, their
      predictive power for the concentrations of antimicrobials in muscle tissue was
      not satisfying. The parameters oxygen saturation, serum lactate concentration and
      the dose per time unit of norepinephrine (noradrenaline) administered showed the
      best correlation with tissue penetration and were used in the TPPS. Its overall
      correlation (r=-0.52, p=0.000007) as well as correlations for the concentrations
      of antimicrobials in muscle (r=-0.46, p=0.006) and adipose tissue (r=-0.59,
      p=0.0003) were better than the currently used scoring systems. CONCLUSION: The
      TPPS may prove to be a powerful tool for the estimation of antimicrobial tissue
      penetration at the bedside in septic patients. This score may allow for adequate
      individual dose adjustment in septic patients. However, this needs to be verified
      in subsequent prospective clinical trials.

PMID- 17201457
TI  - Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ
      transplant recipients.
AB  - This review aims to provide an extensive overview of the literature on the
      clinical pharmacokinetics of mycophenolate in solid organ transplantation and a
      briefer summary of current pharmacodynamic information. Strategies are suggested
      for further optimisation of mycophenolate therapy and areas where additional
      research is warranted are highlighted. Mycophenolate has gained widespread
      acceptance as the antimetabolite immunosuppressant of choice in organ transplant
      regimens. Mycophenolic acid (MPA) is the active drug moiety. Currently, two
      mycophenolate compounds are available, mycophenolate mofetil and enteric-coated
      (EC) mycophenolate sodium. MPA is a potent, selective and reversible inhibitor of
      inosine monophosphate dehydrogenase (IMPDH), leading to eventual arrest of T- and
      B-lymphocyte proliferation. Mycophenolate mofetil and EC-mycophenolate sodium are
      essentially completely hydrolysed to MPA by esterases in the gut wall, blood,
      liver and tissue. Oral bioavailability of MPA, subsequent to mycophenolate
      mofetil administration, ranges from 80.7% to 94%. EC-mycophenolate sodium has an
      absolute bioavailability of MPA of approximately 72%. MPA binds 97-99% to serum
      albumin in patients with normal renal and liver function. It is metabolised in
      the liver, gastrointestinal tract and kidney by uridine diphosphate
      gluconosyltransferases (UGTs). 7-O-MPA-glucuronide (MPAG) is the major metabolite
      of MPA. MPAG is usually present in the plasma at 20- to 100-fold higher
      concentrations than MPA, but it is not pharmacologically active. At least three
      minor metabolites are also formed, of which an acyl-glucuronide has
      pharmacological potency comparable to MPA. MPAG is excreted into the urine via
      active tubular secretion and into the bile by multi-drug resistance protein 2
      (MRP-2). MPAG is de-conjugated back to MPA by gut bacteria and then reabsorbed in
      the colon. Mycophenolate mofetil and EC-mycophenolate sodium display linear
      pharmacokinetics. Following mycophenolate mofetil administration, MPA maximum
      concentration usually occurs in 1-2 hours. EC-mycophenolate sodium exhibits a
      median lag time in absorption of MPA from 0.25 to 1.25 hours. A secondary peak in
      the concentration-time profile of MPA, due to enterohepatic recirculation, often
      appears 6-12 hours after dosing. This contributes approximately 40% to the area
      under the plasma concentration-time curve (AUC). The mean elimination half-life
      of MPA ranges from 9 to 17 hours. MPA displays large between- and within-subject
      pharmacokinetic variability. Dose-normalised MPA AUC can vary more than 10-fold.
      Total MPA concentrations should be interpreted with caution in patients with
      severe renal impairment, liver disease and hypoalbuminaemia. In such individuals,
      MPA and MPAG plasma protein binding may be altered, changing the fraction of free
      MPA available. Apparent oral clearance (CL/F) of total MPA appears to increase in
      proportion to the increased free fraction, with a reduction in total MPA AUC.
      However, there may be little change in the MPA free concentration. Ciclosporin
      inhibits biliary excretion of MPAG by MRP-2, reducing enterohepatic recirculation
      of MPA. Exposure to MPA when mycophenolate mofetil is given in combination with
      ciclosporin is approximately 30-40% lower than when given alone or with
      tacrolimus or sirolimus. High dosages of corticosteroids may induce expression of
      UGT, reducing exposure to MPA. Other co-medications can interfere with the
      absorption, enterohepatic recycling and metabolism of mycophenolate. Most
      pharmacokinetic investigations of MPA have involved mycophenolate mofetil rather
      than EC-mycophenolate sodium therapy. In population pharmacokinetic studies, MPA
      CL/F in adults ranges from 14.1 to 34.9 L/h (ciclosporin co-therapy) and from
      11.9 to 25.4 L/h (tacrolimus co-therapy). Patient bodyweight, serum albumin
      concentration and immunosuppressant co-therapy have a significant influence on
      CL/F. The majority of pharmacodynamic data on MPA have been obtained in patients
      receiving mycophenolate mofetil therapy in the first year after kidney
      transplantation. Low MPA AUC is associated with increased incidence of biopsy
      proven acute rejection. Gastrointestinal adverse events may be dose related.
      Leukopenia and anaemia have been associated with high MPA AUC, trough
      concentration and metabolite concentrations in some, but not all, studies. High
      free MPA exposure has been identified as a risk factor for leukopenia in some
      investigations. Targeting a total MPA AUC from 0 to 12 hours (AUC12) of 30-60
      mg.hr/L is likely to minimise the risk of acute rejection and may reduce
      toxicity. IMPDH monitoring is in the early experimental stage. Individualisation
      of mycophenolate therapy should lead to improved patient outcomes. MPA AUC12
      appears to be the most useful exposure measure for such individualisation.
      Limited sampling strategies and Bayesian forecasting are practical means of
      estimating MPA AUC12 without full concentration-time profiling. Target
      concentration intervention may be particularly useful in the first few months
      post-transplant and prior to major changes in anti-rejection therapy. In patients
      with impaired renal or hepatic function or hypoalbuminaemia, free drug
      measurement could be valuable in further interpretation of MPA exposure.

PMID- 17201461
TI  - Human amygdala activity during the expression of fear responses.
AB  - The initial learning and subsequent behavioral expression of fear are often
      viewed as independent processes with potentially unique neural substrates.
      Laboratory animal studies of Pavlovian fear conditioning suggest that the
      amygdala is important for both forming stimulus associations and for subsequently
      expressing learned behavioral responses. In the present article, human amygdala
      activity was studied during the autonomic expression of conditional fear in two
      differential conditioning experiments with event-related functional magnetic
      resonance imaging and concurrent recording of skin conductance responses (SCRs).
      Trials were classified on the basis of individual participants' SCRs. Significant
      amygdala responding was detected only during trials on which a signal both
      predicted shock and elicited significant conditional SCR. Conditional stimulus
      presentation or autonomic activity alone was not sufficient. These results
      indicate that amygdala activity may specifically reflect the expression of
      learned fear responses and support the position that this region plays a central
      role in the expression of emotional reactions.

PMID- 17201460
TI  - Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected
      patients without liver function impairment: influence of liver fibrosis.
AB  - BACKGROUND AND OBJECTIVE: To assess the influence of hepatitis C virus (HCV) co
      infection and the extent of liver fibrosis on lopinavir/ritonavir
      pharmacokinetics in HIV-infected patients without liver function impairment.
      METHODS: Cross-sectional, comparative study enrolling HIV-infected adults
      receiving lopinavir/ritonavir (400 mg/100 mg twice daily). HIV/HCV co-infected
      patients were grouped as having advanced fibrosis (HCV+/FIB+, n=7) or not
      (HCV+/FIB-, n=8) based on the FIB-4 index. A full concentration-time profile was
      obtained for each patient, and blood samples were collected before (0), and 1, 2,
      4, 6, 8, 10 and 12 hours after a lopinavir/ritonavir dose. Lopinavir and
      ritonavir concentrations in plasma were determined by high-performance liquid
      chromatography. Maximum and minimum plasma concentrations (Cmax and Cmin), area
      under the plasma concentration-time curve from 0 to 12 hours (AUC12), apparent
      oral clearance at steady state (CLss/F), and apparent volume of distribution
      after oral administration (Vd/F) were calculated for each individual using a non
      compartmental approach. RESULTS: Twenty-six HCV- and 22 HCV+patients were
      enrolled. Lopinavir and ritonavir pharmacokinetics were comparable between HCV-
      and HCV+patients. However, the Vd/F of lopinavir was 125% higher in
      HCV+/FIB+patients than in HCV-patients (p=0.015) and 107% higher than in HCV+/FIB
      (p=0.040) patients. The CLss/F of ritonavir was 40% lower in HCV+/FIB+patients
      than in HCV-patients (p=0.005) and 44% lower than in HCV+/FIB-patients (p=0.040).
      Thus, for ritonavir AUC12, Cmax and Cmin in HCV+/FIB+patients were 63%, 86% and
      100% higher, respectively, when compared with those parameters in HCV-patients
      (p=0.005, p=0.012 and p=0.015, respectively), and 80%, 86% and 100% higher,
      respectively, when compared with levels in HCV+/FIB- patients (p=0.040, p=0.040
      and p=0.029, respectively). CONCLUSION: Lopinavir exposure is similar in HIV
      infected patients with or without HCV co-infection and without liver function
      impairment. However, ritonavir exposure may be higher in this setting,
      particularly in individuals with advanced liver fibrosis.

PMID- 17201462
TI  - Fear conditioning and extinction: influence of sex and menstrual cycle in healthy
      humans.
AB  - Although sex differences have been demonstrated in behavioral paradigms of fear
      conditioning, the findings have been inconsistent, and fear extinction has been
      little studied. The present study investigated the influence of sex and menstrual
      cycle phase on the recall of fear extinction. Three groups of healthy adult
      participants were studied: women at 2 different phases of the menstrual cycle
      (early follicular [early cycle] and late follicular [midcycle]) and men.
      Participants underwent a 2-day fear conditioning and extinction protocol. The
      paradigm entailed habituation, fear conditioning, and extinction learning on Day
      1 and extinction recall and fear renewal on Day 2. Skin conductance served as the
      dependent variable. During fear acquisition on Day 1, men showed significantly
      larger conditioned responses relative to women; early cycle and midcycle women
      did not differ. No significant group differences were found during extinction
      learning. On Day 2, men and early cycle women expressed greater extinction memory
      than midcycle women. These data confirm sex differences in conditioned fear
      acquisition and suggest that midcycle hormones attenuate extinction recall.

PMID- 17201463
TI  - Enhanced memory performance on an internal-internal source monitoring test
      following acute psychosocial stress.
AB  - Research on the effect of acute stress and high levels of glucocorticoids on
      memory has largely focused on memory tasks involving the medial temporal lobe
      (e.g., declarative memory). Less is known, however, about the effects of stress
      and glucocorticoids on more strategic memory processes regulated by the
      prefrontal cortex (e.g., source monitoring). In the current study, the authors
      investigated whether exposure to acute psychosocial stress would result in
      altered source monitoring performance relative to the performance of a
      nonstressed control group. To this end, the authors assigned nonsmoking, healthy,
      young men to either a stress (n = 22) or a control (n = 18) condition, after
      which the men were given an internal source monitoring test. Results show that
      relative to control participants, stressed participants made fewer source
      monitoring errors. This study suggests that stress may have differential effects
      on memory, depending on whether the memory test is regulated by the prefrontal
      cortex or the medial temporal lobe.

PMID- 17201464
TI  - Illusory changes in head position induced by neck muscle vibration can alter the
      perception of elbow position.
AB  - Acuity for elbow joint position sense (JPS) is reduced when head position is
      modified. Movement of the head is associated with biomechanical changes in the
      neck and shoulder musculoskeletal system, which may explain changes in elbow JPS.
      The present study aimed to determine whether elbow JPS is also influenced by
      illusory changes in head position. Simultaneous vibration of sternocleidomastoid
      (SCM) and the contralateral splenius was applied to 14 healthy adult human
      subjects. Muscle vibration or passive head rotation was introduced between
      presentation and reproduction of a target elbow position. Ten out of 14 subjects
      reported illusions consistent with lengthening of the vibrated muscles. In these
      10 subjects, absolute error for elbow JPS increased with left SCM/right splenius
      vibration but not with right SCM/left splenius vibration. Absolute error also
      increased with right rotation, with a trend for increased error with left
      rotation. These results demonstrated that both actual and illusory changes in
      head position are associated with diminished acuity for elbow JPS, suggesting
      that the influence of head position on upper limb JPS depends, at least
      partially, on perceived head position.

PMID- 17201465
TI  - The human mu-opioid receptor gene polymorphism 118A > G decreases cortical
      activation in response to specific nociceptive stimulation.
AB  - The authors sought to investigate the role of a common single nucleotide
      polymorphism in the mu-opioid receptor gene (OPRM1) 118A > G for nociceptive
      sensory processing using event-related potentials (ERPs). Specific nociceptive
      (carbon dioxide [CO-sub-2]: 40% volume-to-volume [vol/vol] and 60% vol/vol) and
      nonnociceptive (hydrogen sulfide, 2 parts per million [ppm] and 4 ppm) stimuli
      were applied to the nasal mucosa of 45 volunteers. ERPs were recorded from a
      central lead. In this random sample, we found 37 noncarriers, 7 heterozygous
      carriers, and 1 homozygous carrier of the variant OPRM1 118G allele (allelic
      frequency, 10%). Amplitudes of nociceptive ERP in carriers of this allele were,
      on average, half as high as those of noncarriers. In discriminant analysis, ERP
      amplitude N1 response to the weaker nociceptive stimuli was the only ERP
      parameter that discriminated statistically significantly between carriers and
      noncarriers of the variant 118G allele. On the basis of N1-CO-sub-2 (40%
      vol/vol), the authors correctly backclassified 68.6% of the cases as carriers or
      noncarriers of the allele. The OPRM1 118A > G polymorphism specifically modulates
      nociceptive but not nonnociceptive cortical activation.

PMID- 17201466
TI  - 17-Beta estradiol administration attenuates deficits in sustained and divided
      attention in young ovariectomized rats and aged acyclic female rats.
AB  - Recent evidence suggests that estrogen may interact with the basal forebrain
      cholinergic system to influence learning. The authors examined whether the loss
      of estrogen following ovariectomy (Experiment 1) or the disruption to the
      estrogen cycle during aging (Experiment 2) impaired performance of the 5-choice
      serial reaction time task (5-CSRT)--a sustained and divided attention task
      sensitive to cholinergic challenges in rats. In Experiment 1, posttraining
      ovariectomy in young rats did not disrupt baseline performance but did impair
      performance when attention was challenged by variation in the intertrial interval
      (ITI) or in the intermittent presentation of a novel distracting auditory
      stimulus. Administration of 17-beta estradiol rescued these impairments. Through
      the use of a within-subjects design, Experiment 2 revealed that 17-beta estradiol
      did not influence the baseline performance of 21-month-old female rats trained on
      the 5-CSRT task from a young age but did improve performance when attention was
      challenged by varying the ITI or by presenting a distracting auditory cue. The
      results indicate that 17-beta estradiol administration can improve specific
      components of attention in young ovariectomized rats and gonadally intact aged
      female rats.

PMID- 17201467
TI  - Feeding differences in pubertal and aged golden hamsters (Mesocricetus auratus)
      are related to specific cerebral expression pattern of histamine subtype 3
      receptor.
AB  - The hibernating golden hamster (Mesocricetus auratus) is becoming a useful rodent
      model to study the neurophysiological role of some neuromediators on vital
      behaviors such as sleep and thermoregulation. Recent works have shown that the
      histamine neuroreceptor subtypes (H-sub(1-3)R) are able to modulate such
      behaviors. Here, specific subtype(s) and cerebral nuclei that were actively
      operating on feeding behaviors in pubertal and adult hamsters were identified. Of
      the subtypes assessed, H-sub-3R antagonist (thioperamide) provoked significant (p
      < .001) changes in behavior (very low total food and water intake) in adults,
      whereas it did not significantly modify these behaviors in pubertals. The H-sub
      3R antagonist's role seemed to be related to elevated amounts of stress-induced
      damaged neurons displaying, mainly, shrunken crenated cell membranes and altered
      synaptic processes in limbic areas such as amygdala, cortex, and hippocampus. At
      the transcription level, an evident expression pattern of H-sub-3R messenger RNA
      appeared in pubertals, especially in neurons of the cortex and hippocampus,
      whereas the same trend was featured in amygdalar areas of hibernating adult
      hamsters, suggesting early H-sub-3R regulatory activities, at least in limbic
      sites of this rodent model.

PMID- 17201468
TI  - Prolonged alterations in the serotonin neural system following the cessation of
      adolescent anabolic-androgenic steroid exposure in hamsters (Mesocricetus
      auratus).
AB  - In hamsters (Mesocricetus auratus), anabolic-androgenic steroid (AAS) exposure
      during adolescence facilitates offensive aggression that is modulated, in part,
      by serotonin (5-HT) signaling and development and by signaling and expression of
      5-HT1B receptors. To examine whether these effects are persistent or reversible,
      the authors administered AAS to hamsters, then examined them for aggression at 1,
      4, 11, 18, or 25 days following cessation of AAS treatment. Then, 1 day later,
      hamsters were killed by transcardial perfusion and examined for 5-HT afferents to
      and 5-HT1B receptor-containing neuronal puncta and somata in areas of the brain
      altered by AAS, namely, the anterior hypothalamus, ventrolateral hypothalamus,
      and medial amygdala. Although aggression resulting from AAS exposure returned to
      control, nonaggressive levels by 18 days following cessation of AAS treatment,
      alterations in 5-HT afferent innervation and 5-HT1B receptor localization were
      observed throughout the extended time period examined. These data suggest that
      adolescent AAS exposure may have long-term, irreversible effects on 5-HT neural
      systems and that return to nonaggressive behavioral phenotypes following
      adolescent AAS exposure may not be a function of plasticity in central 5-HT
      systems.

PMID- 17201469
TI  - The role of CA3 and CA1 in the acquisition of an object-trace-place paired
      associate task.
AB  - The hippocampus mediates associative learning involving spatial and temporal
      information. Specifically, paired associations in which a trace interval
      separates the elements appear to be associated within CA1. In contrast, CA3
      appears to be involved in associations containing spatial elements. This suggests
      that CA3, but not CA1, is involved as long as the spatial association does not
      contain temporal elements; conversely, CA1 is involved when a temporal element is
      included, regardless of whether there are spatial elements present. In the
      present study, rats were run on an object-trace-place paired-associate learning
      paradigm. Rats with CA3 as well as rats with CA1 lesions showed deficits in the
      acquisition of this task. These results suggest that CA1 is involved in making
      arbitrary associations involving a temporal (trace) element, whereas CA3 is
      involved in making associations that involve spatial elements; furthermore, CA1
      and CA3 interact in the presence of both spatial and temporal information.

PMID- 17201472
TI  - Comparison of nutritive and nonnutritive stimuli in intestinal and oral
      conditioned taste aversion paradigms.
AB  - The intestinal taste aversion paradigm has previously demonstrated that animals
      could orally discriminate between carbohydrate and fat subsequent to pairing a
      gastrointestinal (GI) infusion of 1 nutrient with lithium chloride (LiCl),
      whereas they could not discriminate between 2 nonnutritive flavors (A. L. Tracy,
      R. J. Phillips, M. M. Chi, T. L. Powley, & T. L. Davidson, 2004). The present
      experiments assessed the relative salience of nutritive and nonnutritive stimuli
      when presented either intestinally or orally. Two compound stimuli, each
      comprising 1 nutrient and 1 nonnutritive flavor, were presented in training and
      were paired with LiCl or saline. Subsequent oral intake of the nutrients alone,
      the flavors alone, or the compounds was measured. Results showed that rats
      discriminated both nutrients and flavors independently after GI or oral training,
      whereas the compounds were discriminated only after oral training, indicating
      substantive differences in the processing of these stimuli. This suggests that
      nutrient activation of the GI tract may potentiate learning about nonnutritive
      flavors analogously to taste-potentiated odor conditioning. The ability to learn
      about the oral properties of stimuli in the GI tract suggests a new account of
      delayed taste aversion learning as well as learning about the positive nutritive
      consequences of food consumption.

PMID- 17201470
TI  - Effects of lesions of the bed nucleus of the stria terminalis, lateral
      hypothalamus, or insular cortex on conditioned taste aversion and conditioned
      odor aversion.
AB  - The effects of permanent forebrain lesions on conditioned taste aversions (CTAs)
      and conditioned odor aversions (COAs) were examined in 3 experiments. In
      Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence
      on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced
      severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs
      or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA
      acquisition but had no influence on COA acquisition. The implications of these
      findings are discussed with regard to the forebrain influence on parabrachial
      nucleus function during CTA acquisition.

PMID- 17201473
TI  - Place learning strategy of substantia nigra pars compacta-lesioned rats.
AB  - The substantia nigra pars compacta (SNc) and the dorsal striatum are often
      considered to be necessary for stimulus-response (S-R) habit learning, whereas
      the dorsal hippocampus is considered to be necessary for relational (declarative)
      memory. Spatial learning is a kind of relational learning that occurs when a rat
      is released from different locations (variable start) in a water maze to find a
      submerged platform that is kept in a constant location. However, when the rat is
      always released from the same starting position (constant start), it can learn to
      find the platform oriented by a fixed configuration of cues, that is, by S-R
      learning. To test the critical role of the SNc in S-R and relational learning,
      the authors tested adult male Wistar rats, sham-operated or with a lesion in the
      SNc, in these 2 versions of the water maze task. The SNc lesion was induced by
      bilateral intranigral infusion of 0.5 micromol 1-methyl-4-phenyl- 1,2,3,6
      tetrahydropyridine. Although the SNc-lesioned rats learned the variable-start
      version as effectively as sham rats did, they were significantly impaired in
      learning the constant-start version of the task.

PMID- 17201474
TI  - Long-term functional outcome following transient middle cerebral artery occlusion
      in the rat: correlation between brain damage and behavioral impairment.
AB  - The assessment of both histological and functional long-term outcomes after
      cerebral ischemia is increasingly recommended for preclinical studies. Whereas
      correlations between behavioral impairments and primary ischemic lesion are
      documented, little is known about their relationships with remote nonischemic
      regions that undergo secondary degeneration, such as the thalamus. Anesthetized
      rats were subjected to mild (30 min) or severe (60 min) occlusion of the middle
      cerebral artery. Two months after ischemia, sensorimotor behavior was assessed
      according to the neurological score, limb-placing, adhesive-removal, and
      staircase tests; the final histological lesion was measured after this
      assessment. Cortical damage was correlated to all transient and long-lasting
      sensorimotor deficits, whereas striatal lesion was more consistently reflected by
      the forelimb-placing reflexes and adhesive-removal motor deficits. By contrast,
      the thalamic atrophy was not correlated to early neurological impairment, but
      rather to the late sensory deficit at the adhesive-removal test and to the
      skilled forepaw reaching alteration at the staircase test. This suggests that
      thalamus contributes, albeit moderately, to the ischemia-induced long-lasting
      sensorimotor deficits, some of which represent relevant targets for therapeutic
      interventions.

PMID- 17201475
TI  - Orbital frontal cortex ablations of rock squirrels (Spermophilus variegatus)
      disinhibit innate antisnake behavior.
AB  - The antisnake behavior of rock squirrels (Spermophilus variegatus) was examined
      to determine the role of the orbital frontal cortex in regulating physiological
      arousal and behavioral excitability during encounters with a rattlesnake
      predator. Rock squirrels with orbital frontal cortex ablations and sham-surgery
      control squirrels were presented with a caged rattlesnake pre- and postsurgery.
      Orbital frontal cortex ablations had no substantial effect on the expression of
      gross motor behavior in dealing with the rattlesnake, but they augmented the
      speed of snake recognition and clearly disinhibited sympathetic arousal as
      manifested by increased tail piloerection and tail-flagging activity, which is a
      specific antisnake behavior. Natural selection from snakes has probably shaped
      the neural organization of the orbital frontal cortex to afford adaptive
      behavioral flexibility during snake encounters.

PMID- 17201476
TI  - Effects of labor contractions on catecholamine release and breathing frequency in
      newborn rats.
AB  - Plasma catecholamines in newborn rats (0-2 hr old) were analyzed following
      vaginal birth, cesarean section with simulated labor contractions, or cesarean
      section without labor contractions. Upon delivery, pups were exposed to key
      elements of the rat's natural birth process, that is, umbilical cord occlusion,
      tactile stimulation, and cooling. Only pups exposed to actual or simulated labor
      showed an immediate rise in norepinephrine and epinephrine. Initial postpartum
      respiratory frequencies were higher in vaginal than in cesarean delivered pups
      and, in all groups, inversely correlated with catecholamine titers, suggesting
      respiratory distress or transient tachypnea at lower catecholamine levels. These
      findings establish a rat model for analyzing effects of labor on neonatal
      adaptive response during the transition from prenatal to postnatal life.

PMID- 17201477
TI  - Prenatally elevated physiological arousal interferes with perceptual learning in
      bobwhite quail (Colinus virginianus) embryos.
AB  - Neonatal studies suggest elevated arousal can negatively influence perceptual and
      cognitive processes during early development. The authors explored this issue
      during the prenatal period by pharmacologically elevating physiological arousal
      in bobwhite quail (Colinus virginianus) embryos during exposure to a maternal
      call, then assessing preference for the familiar call following hatching. Embryos
      receiving norepinephrine showed a prenatal elevation in heart rate and failed to
      demonstrate a preference for the familiar call following hatching. Embryos not
      receiving norepinephrine showed no elevation in heart rate and demonstrated a
      preference for the familiar call. These results indicate elevated arousal can
      interfere with perceptual learning during the prenatal period and provide
      additional evidence for an optimal window of arousal necessary to foster species
      typical perceptual functioning during early development.

PMID- 17201478
TI  - Lesions to the medial preoptic nucleus differentially affect singing and nest box
      directed behaviors within and outside of the breeding season in European
      starlings (Sturnus vulgaris).
AB  - Little is known about how the brain regulates context-appropriate communication.
      European starlings produce song in various social contexts. During the breeding
      season, males with nest sites sing high levels of sexually motivated song in
      response to a female. Outside of this context, song rates are not affected by
      female presence. The medial preoptic nucleus (POM) regulates male sexual
      behavior, and studies in songbirds implicate the POM in sexually motivated song.
      Recent data suggest that the role of the POM might extend to song produced in
      other contexts as well. To examine this possibility, effects of bilateral
      electrolytic lesions of the POM on singing and other behaviors in adult male
      starlings within sexually relevant and nonsexual contexts were studied. Lesions
      to the POM exclusively reduced song and nest box-directed behaviors within highly
      sexually relevant contexts. Unexpectedly, POM lesions increased song in a
      nonsexual context, suggesting an inhibitory role for the POM in this context.
      These data suggest that the POM interacts with the song control system so that
      song occurs in an appropriate social context in response to appropriate stimuli.

PMID- 17201480
TI  - Odorant identification and quality perception following methyl bromide-induced
      lesions of the olfactory epithelium.
AB  - Using a 5-odorant identification confusion matrix task, the authors assessed the
      consequence of olfactory epithelial damage on odorant quality perception in the
      rat. After establishing prelesion identification performance, each rat's
      epithelium was subjected to 330 ppm methyl bromide gas for 6 hr. Comparison of
      prelesion and 3-day postlesion performance demonstrated a significant decrease in
      identification as a consequence of 95%-98% epithelial destruction. Further, there
      was a differential effect of lesion on the ability of different animals to
      identify the different individual odorants. Evaluation of the anatomical state of
      the epithelium relative to performance on the identification task demonstrated a
      significant relationship between the extent and location of anatomical sparing
      and changes in individual odorant identifications. Assessment of pre- and
      postlesion quality perception for the individual rats demonstrated a highly
      significant shift in quality perception that was independent of any decrease in
      performance. These results provide strong support for the proposition that the
      regional variations in mucosal sensitivities within and across olfactory receptor
      gene expression zones are fundamentally important for the encoding of odorant
      quality.

PMID- 17201479
TI  - Predicting odorant quality perceptions from multidimensional scaling of olfactory
      bulb glomerular activity patterns.
AB  - Odorants and their perceptions differ along multiple dimensions, requiring that a
      critical examination of any putative neural code directly assess the
      multidimensional nature of the encoding process. Previous work has examined
      simple, systematic odorant differences that, regardless of coding strategy, would
      be expected to produce simple, systematic predictions in neural and behavioral
      responses. In the present study, an odorant identification confusion matrix task
      that extracts precise quality relationships across odorants was used to determine
      whether spatially specific glomerular activity patterns predict perceptual
      quality relationships for odorants that cannot easily be classified a priori
      along a single chemical dimension. Multidimensional scaling (MDS) analysis of
      odorant pattern similarity measures derived from the comparison of [14C]-2
      deoxyglucose glomerular activity pattern data yielded a two-dimensional odorant
      activity space that was highly significantly predictive of similarly obtained
      odorant perceptual spaces, uniformly across animals. These results strongly
      support the relevance of global spatial patterns in the olfactory bulb to the
      encoding of odor quality.

PMID- 17201481
TI  - Ethanol-related traits in mice selectively bred for differential sensitivity to
      methamphetamine-induced activation.
AB  - Acute drug stimulation has been proposed to be an endophenotype for drug abuse.
      The authors previously reported the short-term selective breeding of lines of
      mice for low (LMACT) and high (HMACT) stimulation to methamphetamine (MA). These
      mice were used to examine whether common genes influence the locomotor response
      to MA and ethanol. Additionally, the authors tested these mice for ethanol
      drinking, locomotor sensitization, and clearance. LMACT mice were less stimulated
      by ethanol and consumed more ethanol than HMACT mice, but the lines did not
      differ in ethanol-induced sensitization. A small difference in ethanol clearance
      rate (0.1 mg/ml/h) likely had little impact on behavior. Some common genes may
      influence the locomotor response to MA and ethanol, as well as ethanol drinking.

PMID- 17201482
TI  - Attentional dysfunction, impulsivity, and resistance to change in a mouse model
      of fragile X syndrome.
AB  - On a series of attention tasks, male mice with a mutation targeted to the fragile
      X mental retardation 1 (Fmrl) gene (Fmrl knockout [KO] mice) committed a higher
      rate of premature responses than wild-type littermates, with the largest
      differences seen when task contingencies changed. This finding indicates impaired
      inhibitory control, particularly during times of stress or arousal. The KO mice
      also committed a higher rate of inaccurate responses than controls, particularly
      during the final third of each daily test session, indicating impaired sustained
      attention. In the selective attention task, the unpredictable presentation of
      potent olfactory distractors produced a generalized disruption in the performance
      of the KO mice, whereas for controls, the disruption produced by the distractors
      was temporally limited. Finally, the attentional disruption seen following an
      error was more pronounced for the KO mice than for controls, further implicating
      impaired regulation of arousal and/or negative affect. The present study provides
      the first evidence that the Fmrl KO mouse is impaired in inhibitory control,
      attention, and arousal regulation, hallmark areas of dysfunction in fragile X
      syndrome. The resistance to change also seen in these mice provides a behavioral
      index for studying the autistic features of this disorder.

PMID- 17201483
TI  - Aggressive male APP23 mice modeling behavioral alterations in dementia.
AB  - In addition to cognitive deterioration, Alzheimer's disease patients exhibit
      behavioral and psychological signs and symptoms of dementia. Behavioral
      alterations are a major source of caregiver stress and an important contributor
      in the decision to institutionalize patients. The amyloid precursor protein (APP)
      23 transgenic mouse model develops amyloid plaques from the age of 6 months
      onward and exhibits tau pathology, which is absent in most other amyloid-based
      models. Besides mimicking the demented patients' memory deficits, these
      transgenic mice present with various behavioral disturbances, thereby
      approximating the clinical situation remarkably well. Using an isolation
      induced/resident-intruder paradigm of aggression, the authors revealed increased
      aggressiveness in male APP23 mice at the ages of 6 and 12 months. The presence of
      aggressive disturbances in this valuable mouse model opens perspectives to
      evaluate aggression-modulating therapies.

PMID- 17201484
TI  - Profile of immediate early gene expression in the lumbar spinal cord of low
      thoracic paraplegic mice.
AB  - Induction of immediate early gene (IEG) expression is believed to constitute one
      of the earliest steps in plasticity and long-term modification of neuronal
      properties. Although behavioral evidence of neuronal plasticity at the
      sublesional level after spinal cord injury exists, spatiotemporal changes of IEGs
      in spinal segments located caudally to such an injury have never been examined.
      Here, the authors studied spatiotemporal changes of c-fos, nor-1, nur77, nurr1,
      and retinoid x receptor (rxr) messenger RNA expression in the lumbar segments L1
      L2 after low-thoracic spinal transection (Tx). C-fos expression generally
      increased in the dorsal horn with significant levels reached at 3 days and 14
      days post-Tx. Basal nor-1 transcript levels decreased in the intermediate zone
      and dorsal horn areas at 7 days. Nur77 levels were nonsignificantly depressed
      throughout that period of time, whereas nurr1 and rxr transcripts were not
      detected before or after Tx. In conclusion, the results provide evidence of
      distinct roles for c-fos and nor-1 in reorganization and plasticity of neuronal
      networks typically involved in sensorimotor integration and locomotor control.

PMID- 17201485
TI  - Sexual experience increases nitric oxide synthase in the medial preoptic area of
      male rats.
AB  - Nitric oxide in the medial preoptic area (MPOA) is important for the expression
      and sensitization of male sexual behavior. In this article, the authors report
      that repeated sexual experience (mating for 2 hr on each of 3 days) increased
      levels of nitric oxide synthase (NOS) in the MPOA of male rats, regardless of
      whether they mated on the day they were given an overdose of sodium
      phenobarbital. This effect resulted from the previous experience and not acute
      mating, as NOS was not increased 2 hr after the first mating in previously naive
      males. Experience-induced increases in NOS in the MPOA may be one mechanism
      through which sexual experience facilitates sexual behavior in male rats.

PMID- 17201486
TI  - Anterior cingulate activity and level of cognitive conflict: explicit
      comparisons.
AB  - The role of anterior cingulate cortex (ACC) in attention is a matter of debate.
      One hypothesis suggests that its role is to monitor response-level conflict, but
      explicit evidence is somewhat lacking. In this study, the activation of ACC was
      compared in (a) color and number standard Stroop tasks in which response
      preparation and interference shared modality (response-level conflict) and (b)
      color and number matching Stroop tasks in which response preparation and
      interference did not share modality (non-response-level conflict). In the
      congruent conditions, there was no effect of task type. In the interference
      conditions, anterior cingulate activity in the matching tasks was less than that
      in the standard tasks. These results support the hypothesis that ACC specifically
      mediates generalized modality-independent selection processes invoked by response
      competition.

PMID- 17201488
TI  - Developmental changes in personal goal orientation from young to late adulthood:
      from striving for gains to maintenance and prevention of losses.
AB  - Using a multimethod approach, the authors conducted 4 studies to test life span
      hypotheses about goal orientations across adulthood. Confirming expectations, in
      Studies 1 and 2 younger adults reported a primary growth orientation in their
      goals, whereas older adults reported a stronger orientation toward maintenance
      and loss prevention. Orientation toward prevention of loss correlated negatively
      with well-being in younger adults. In older adults, orientation toward
      maintenance was positively associated with well-being. Studies 3 and 4 extend
      findings of a self-reported shift in goal orientation to the level of behavioral
      choice involving cognitive and physical fitness goals. Studies 3 and 4 also
      examine the role of expected resource demands. The shift in goal orientation is
      discussed as an adaptive mechanism to manage changing opportunities and
      constraints across adulthood.

PMID- 17201487
TI  - A systemic-wholistic approach to differential aging: longitudinal findings from
      the Berlin Aging Study.
AB  - Wholistic perspectives on differential change focus on multiple-indicator
      information at a person level. They supplement the modeling of average
      trajectories at a variable level. The authors extended cross-sectional work in
      the Berlin Aging Study (J. Smith & P. B. Baltes, 1997) to 6-year longitudinal
      cluster analyses (n = 132). At baseline, 3 subgroups were identified with
      distinct within-person psychological profiles across cognitive, personality, and
      social integration constructs. Over time, highly similar subgroup profiles were
      found, and about two thirds of the participants could be classified as remaining
      in the same subgroups. Baseline subgroups differed in level and slope of change
      and in 2 outcomes, well-being and mortality. Independent of subgroup membership,
      subgroup-to-subgroup change was associated with greater decline and predicted
      poststudy mortality. These findings demonstrate the usefulness of a wholistic
      approach for long-term prediction of outcomes and within-person systemic
      variability.

PMID- 17201489
TI  - Using the concept of wisdom to enhance the expression of wisdom knowledge: not
      the philosopher's dream but differential effects of developmental preparedness.
AB  - In this study, the authors explored whether wisdom-related performance could be
      enhanced by an instruction referring to the abstract concept of wisdom ("try to
      give a wise response"). The authors used three levels of activation of the
      concept of wisdom as well as intelligence-activation and control conditions in a
      heterogeneous sample of three age groups (N = 318). Results showed no general
      effect of the wisdom-concept instructions but did show an aptitude (resource)
      treatment interaction: Participants high in preparedness resources associated
      with wisdom exhibited some gains, whereas the performance of resource-low
      participants actually declined after the instruction. Implications and
      consequences with respect to ways of enhancing the expression of wisdom-related
      knowledge are discussed.

PMID- 17201490
TI  - An age apart: the effects of intergenerational contact and stereotype threat on
      performance and intergroup bias.
AB  - An experimental study examined the effect of intergenerational contact and
      stereotype threat on older people's cognitive performance, anxiety, intergroup
      bias, and identification. Participants completed a series of cognitive tasks
      under high or low stereotype threat (through comparison with younger people). In
      line with stereotype threat theory, threat resulted in worse performance.
      However, this did not occur if prior intergenerational contact had been more
      positive. This moderating effect of contact was mediated by test-related anxiety.
      In line with intergroup contact theory, more positive contact was associated with
      reduced prejudice and reduced ingroup identification. However this occurred in
      the high threat, but not low threat, condition. The findings suggest that
      positive intergenerational contact can reduce vulnerability to stereotype threat
      among older people.

PMID- 17201491
TI  - Modeling late-life adaptation in affective well-being under a severe chronic
      health condition: the case of age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) was used as a case model to longitudinally
      study adaptation in affective well-being under a prevalent chronic health
      condition. Measures of positive and negative affect, obtained at 5 subsequent
      measurement occasions with 3-month intervals in between, were analyzed in 90
      older adults diagnosed with AMD. The authors proposed a pattern of adaptation
      that shows initial decline in affective well-being after disease outbreak,
      followed by a turnaround into a restorative phase of increase, implying nonlinear
      intraindividual trajectories, with changes substantially related to disease
      duration. Analysis was conducted by means of a nonlinear mixed models approach.
      Results confirmed the hypothesized adaptation pattern for positive affect but not
      for negative affect, which was found more stable across measurement occasions.

PMID- 17201492
TI  - Dealing with negative social exchanges in later life: coping responses, goals,
      and effectiveness.
AB  - Negative exchanges have been shown to detract from psychological well-being in
      later life, but little research has investigated how older adults respond to such
      exchanges. The authors examined older adults' coping responses, goals, and
      effectiveness following a specific negative social exchange. The findings
      revealed that participants' coping responses and the effectiveness of these
      responses varied as a function of their coping goals. The results underscore the
      importance of considering older adults' coping responses and goals when
      evaluating factors that affect the impact of negative social exchanges on well
      being in later life.

PMID- 17201493
TI  - Age differences in the organization of emotion knowledge: effects involving
      valence and time frame.
AB  - Older and younger adults attend to and remember emotion information differently.
      The present study builds on this work by investigating age-related differences in
      the schematic organization of emotion knowledge. Younger and older adults
      reported on their experiences of positive and negative affect, both today and in
      general. Of primary interest was judgment speed as a function of matches (e.g.,
      positive-positive) or mismatches (e.g., negative-positive) in valence and time
      frame across consecutive trials. Older adults exhibited stronger valence-related
      priming effects and weaker time-frame-related priming effects, relative to
      younger adults. Results remained significant when controlling for individual
      differences in speed, speed variability, motor priming, temperament, and life
      satisfaction. The discussion focuses on the manner in which age differences in
      the schematic organization of emotion knowledge might contribute to age
      differences in the self-concept, affective processing, and emotional experience.

PMID- 17201494
TI  - Development and structural dynamics of personal life investment in old age.
AB  - The development of personal life investment (PLI) during old age was investigated
      with longitudinal and cross-sectional data from the Berlin Aging Study (N = 516,
      ages = 70-103 years). PLI measures motivational energy expended in life domains
      that require (obligatory PLI) or do not require (optional PLI) investment in old
      age. The authors used structural modeling to determine developmental trajectories
      and dynamics of the PLI types. On average, obligatory PLI remained unchanged
      between 70 and 101 years. Optional PLI declined during the transition to the 4th
      age (between 80 and 90 years). When change on the intraindividual level was
      considered, reductions in optional PLI were not related to changes in obligatory
      PLI, but declining obligatory PLI was associated with declining optional PLI.

PMID- 17201495
TI  - Visual search for change in older adults.
AB  - Previous research has demonstrated that younger adults are surprisingly poor at
      detecting substantial changes to visual scenes. Little is known, however, about
      age differences in this phenomenon. In the 2 experiments reported here, older
      adults were slower than younger adults in detecting changes to simple visual
      stimuli. This age difference was beyond what would be expected given known age
      related changes in processing speed. Examination of eye movement behavior during
      the search for change suggested that age-related changes in the useful field of
      view and degree of cautiousness play a significant role. Speed of processing and
      3 age-related eye movement behaviors explained 85% of the variance in change
      detection latency, eliminating the effect of age.

PMID- 17201496
TI  - A comparison of higher order auditory processes in younger and older adults.
AB  - The authors conducted 3 experiments investigating the effects of aging on higher
      order auditory processes. They compared younger and older adults with respect to
      (a) their auditory channel capacity, (b) the extent of their top-down control
      over auditory gain, and (c) their ability to focus attention on a narrow band of
      frequencies. To ensure that subclinical cochlear processing deficits in older
      adults (e.g., higher thresholds, poorer discrimination of frequency and intensity
      differences) did not limit performance, the authors used only stimuli that were
      perfectly discriminable by all participants. No age differences were found in any
      of these experiments, suggesting that some higher order auditory processes (e.g.,
      top-down control over auditory gain, auditory attention) are preserved in normal
      aging, despite numerous age-related declines in peripheral auditory
      functionality.

PMID- 17201497
TI  - Cognitive decline in old age: separating retest effects from the effects of
      growing older.
AB  - Repeated administration of cognitive tests improves test performance, making it
      difficult for researchers to gauge the true extent of age-related cognitive
      decline. The authors examined this issue using data from the Rush Religious
      Orders Study and linear mixed-effects models. At annual intervals for up to 8
      years, more than 800 older Catholic clergy members completed the same set of 19
      cognitive tests from which previously established composite measures of cognitive
      domains were derived. Retest effects on some measures were substantial and
      continued to accumulate even after 8 annual test readministrations, but effects
      on other measures were minimal. Across cognitive measures, retest effects were
      not related to age, sex, or education. Individual differences in retest effects
      were substantial but not consistent across cognitive measures. The results
      suggest that retest-based improvement in cognitive test performance can be
      substantial and persistent.

PMID- 17201499
TI  - Lexical competition and phonological encoding in young and older speakers.
AB  - The influence of age on word retrieval was investigated with a speeded picture
      naming study. Five hundred forty-one pictures were presented to young and older
      adults, and the influence of name agreement and name frequency was analyzed by
      multiple regression. The results showed that both name agreement and name
      frequency are significant predictors of picture naming performance in young and
      older adults. The results also suggest that older adults are more strongly
      influenced by name agreement than are young adults. These results indicate that
      competition during lexical selection may be a particularly age-sensitive stage in
      language production.

PMID- 17201498
TI  - Adult age differences in the effects of goals on self-regulated sentence
      processing.
AB  - The authors examined age differences in adults' allocation of effort when reading
      text for either high levels of recall accuracy or high levels of efficiency.
      Participants read a series of sentences, making judgments of learning before
      recall. Older adults showed less sensitivity than the young to the accuracy goal
      in both reading time allocation and memory performance. Memory accuracy and
      differential allocation of effort to unlearned items were age equivalent, so age
      differences in goal adherence were not attributable to metacognitive factors.
      However, comparison with data from a control reading task without monitoring
      showed that learning gains among older adults across trial were reduced relative
      to those of the young by memory monitoring, suggesting that monitoring may be
      resource consuming for older learners. Age differences in the responsiveness to
      (information-acquisition) goals could be accounted for, in part, by independent
      contributions from working memory and memory self-efficacy. Our data suggest that
      both processing capacity ("what you have") and beliefs ("knowing you can do it")
      can contribute to individual differences in engaging resources ("what you do") to
      effectively learn novel content from text.

PMID- 17201500
TI  - Age differences in the sixth personality factor: age differences in interpersonal
      relatedness among Canadians and Hong Kong Chinese.
AB  - Cross-cultural studies on personality in which a combined etic-emic approach has
      been used have found a 6th personality factor--Interpersonal Relatedness--in
      addition to the usual Big Five. The authors examined age differences in
      Interpersonal Relatedness among Canadians and Hong Kong Chinese after
      statistically controlling for the Big Five. Age differences in some aspects of
      Interpersonal Relatedness were found among Hong Kong Chinese but not among
      Canadians, suggesting that development of some personality characteristics may
      differ across cultures.

PMID- 17201501
TI  - The negativity bias is eliminated in older adults: age-related reduction in event
      related brain potentials associated with evaluative categorization.
AB  - Studies of younger adults have found that negative information has a stronger
      influence than positive information across a wide range of domains. T. A. Ito, J.
      T. Larsen, N. K. Smith, and J. T. Cacioppo (1998) reported that during evaluative
      categorization, extreme negative images produced greater brain activity than did
      equally extreme positive images in younger adults. Older adults have been
      reported to optimize affect and attend less to negative information. In this
      article, the negativity bias was examined in 20 older versus 20 younger adults
      during evaluative categorization, with a focus on brain activity occurring
      roughly 500 ms after presentation of visual stimuli. Results demonstrated a
      significant decrease in brain activity to both positive and negative stimuli (p <
      .05) and an elimination of the negativity bias in older adults.

PMID- 17201502
TI  - The influence of emotional valence on age differences in early processing and
      memory.
AB  - This study examined older and younger adults' attentional biases and subsequent
      incidental recognition memory for distracting positive, negative, and neutral
      words. Younger adults were more distracted by negative stimuli than by positive
      or neutral stimuli, and they correctly recognized more negative than positive
      words. Older adults, however, attended equally to all stimuli yet showed reliable
      recognition only for positive words. Thus, although an attentional bias toward
      negative words carried over into recognition performance for younger adults,
      older adults' bias appeared to be limited to remembering positive information.

PMID- 17201503
TI  - Attentional disregulation: a benefit for implicit memory.
AB  - The authors investigated the effect of age and time of testing on the ability to
      control attention and addressed the possibility that older adults' susceptibility
      to distraction may sometimes facilitate performance on a later cognitive task.
      Using a modification of a G. Rees, C. Russell, C. D. Frith, and J. Driver (1999)
      procedure, the authors asked the participants to make same or different judgments
      on line drawings superimposed with task-irrelevant letter strings. Memory for the
      distractors was subsequently tested with an implicit memory task. Both older and
      young adults demonstrated greater memory for distractors at nonoptimal times of
      day than at optimal times of day; however, older adults showed considerably
      better memory for the distractors than did young adults.

PMID- 17201504
TI  - First-time mothers' expectations of parenthood: What happens when optimistic
      expectations are not matched by later experiences?
AB  - Becoming a parent is a major developmental transition of adulthood. Individuals
      often have optimistic expectations about parenthood, yet this transition also
      presents a number of challenges. The authors investigated whether new parents
      have overly optimistic expectations about parenthood and, if they do, how this
      influences their adjustment to this role. The sample consisted of 71 first-time
      mothers who completed questionnaires during pregnancy and at 4 months postpartum.
      The study assessed women's expectations of caring for their infant and the
      influence parenthood would have on their well-being and their relationships with
      others. Most women's expectations were matched or exceeded by their parenting
      experiences. However, where experiences were negative relative to expectations,
      there was greater depression symptomatology and poorer relationship adjustment.

PMID- 17201505
TI  - Gender differences in physical aggression: A prospective population-based survey
      of children before and after 2 years of age.
AB  - There has been much controversy over the past decades on the origins of gender
      differences in children's aggressive behavior. A widely held view is that gender
      differences emerge sometime after 2 years of age and increase in magnitude
      thereafter because of gender-differentiated socialization practices. The
      objective of this study was to test for (a) gender differences in the prevalence
      of physical aggression in the general population of 17-month-old children and (b)
      change in the magnitude of these differences between 17 and 29 months of age.
      Contrary to the differential socialization hypothesis, the results showed
      substantial gender differences in the prevalence of physical aggression at 17
      months of age, with 5% of boys but only 1% of girls manifesting physically
      aggressive behaviors on a frequent basis. The results suggest that there is no
      change in the magnitude of these differences between 17 and 29 months of age.

PMID- 17201506
TI  - Children's emotion regulation: Self-report and physiological response to peer
      provocation.
AB  - The authors examined the notion that children's emotion regulation (ER) is a
      uniform skill by (a) investigating the concordance between self-report of ER and
      physiological measures and by (b) examining ER in a specific context (e.g., peer
      provocation) and context-free manner (e.g., during a semistructured interview of
      ER abilities). Seventy-two children in middle childhood (average age = 9 years)
      participated. Time-locked measures of heart rate reactivity and recovery were
      obtained in response to provoking comments, and vagal regulation was measured
      throughout the provocation session. Children who reported greater dysregulation
      showed increased heart rate reactivity to provocative comments (i.e., steeper
      heart rate slope) but no difference in heart rate recovery. The context-free but
      not the context-specific self-report measure was associated with a failure to
      suppress vagal tone. Implications for ER measurement and children's peer
      relations are discussed.

PMID- 17201507
TI  - The psychophysiology of adult attachment relationships: Autonomic reactivity in
      marital and premarital interactions.
AB  - To better understand the origins of autonomic reactivity during marital
      interactions, this study examined the psychophysiological profiles of
      prototypically secure (vs. insecure) and deactivating (vs. hyperactivating)
      adults while they talked about areas of disagreement with their (pre)marital
      partners. Adults who idealized their caregivers and/or normalized harsh childhood
      experiences during the Adult Attachment Interview (i.e., deactivating adults)
      manifested heightened electrodermal reactivity, a sign of emotional inhibition,
      while attempting to resolve conflict in their relationships, whereas individuals
      who became angrily or passively caught up while discussing their early lives
      (i.e., hyperactivating adults) later showed increases in heart rate while
      conversing with their partners, suggesting behavioral activation. In contrast,
      security was associated with low levels of electrodermal change from baseline in
      the context of this normatively mild marital stressor. Results were generally
      consistent for 40 younger engaged and 40 mature married couples.

PMID- 17201509
TI  - Maternal depression and early positive parenting predict future conduct problems
      in young children with attention-deficit/hyperactivity disorder.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) are at risk for
      adverse outcomes such as substance abuse and criminality, particularly if they
      develop conduct problems. Little is known about early predictors of the
      developmental course of conduct problems among children with ADHD, however.
      Parental psychopathology and parenting were assessed in 108 children who first
      met Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for
      ADHD at 4-7 years old. When demographic variables and baseline ADHD and conduct
      problems were controlled, maternal depression predicted conduct problems 2-8
      years following the initial assessment, whereas positive parenting during the
      structured parent- child interaction task predicted fewer future conduct
      problems. These findings suggest that maternal depression is a risk factor,
      whereas early positive parenting is a protective factor, for the developmental
      course of conduct problems among children with ADHD.

PMID- 17201508
TI  - 12-month-old infants allocate increased neural resources to stimuli associated
      with negative adult emotion.
AB  - Young infants use caregivers' emotional expressions to guide their behavior in
      novel, ambiguous situations. This skill, known as social referencing, likely
      involves at least 3 separate abilities: (a) looking at an adult in an unfamiliar
      situation, (b) associating that adult's emotion with the novel situation, and (c)
      regulating their own emotions in response to the adult's emotional display. The
      authors measured each of these elements individually as well as how they related
      to each other. The results revealed that 12-month-olds allocated more attention,
      as indicated by event-related potential measures, to stimuli associated with
      negative adult emotion than to those associated with positive or neutral emotion.
      Infants' interaction with their caregiver was affected by adult emotional
      displays. In addition, how quickly infants referenced an adult predicted both
      their brain activity in response to pictures of stimuli associated with negative
      emotion as well as some aspects of their behavior regulation. The results are
      discussed with respect to their significance for understanding why infants
      reference and regulate their behavior in response to adult emotion. Suggestions
      for further research are provided.

PMID- 17201510
TI  - Adaptive elements of aging: Self-image discrepancy, perfectionism, and eating
      problems.
AB  - Age-related changes in personality variables that may contribute to the reduction
      of symptoms of eating disorders with adult development were examined.
      Undergraduate sorority women (n = 52; mean age = 19.85 years) were compared with
      alumnae of the same sorority (n = 34; mean age = 33.74 years). Eating pathology
      was correlated with greater discrepancy between the real (current) and the ideal
      (desired) self-image and with perfectionism. Both self-image discrepancy and
      perfectionism were markedly lower among the alumnae. Variance in these variables
      together accounted for the lowered level of eating pathology among the older
      participants. Specific content domains of the real and ideal self-image and
      different facets of perfectionism showed distinctive age-related changes and
      differential relationships with eating pathology.

PMID- 17201511
TI  - The development of context sensitivity in children's graphic copying strategies.
AB  - The authors report on a series of 5 experiments in which 462 5- to 10-year-old
      children and 109 adults were required to copy geometric figures either with no
      constraints or following prior exposure to primes consisting of different
      parsings of the figures. The analysis focused on the graphic strategies adopted
      by the participants to copy the models. Three developmental steps were revealed
      in the baseline copying condition. Priming experiments demonstrated that the age
      developmental step correspondence varied as a function of the type of prime used.
      However, the impact of priming differed according to age. It was limited at 6
      years, whereas its size was noticeable at the other ages. These results are
      discussed in the light of developmental models that hypothesize a major role
      either for endogeneous factors in cognitive development or for exogeneous and
      contextual factors.

PMID- 17201512
TI  - Children's attention to beliefs in interactive persuasion tasks.
AB  - Whether and when children can apply their developing understanding of belief to
      persuasion was examined using interactive puppet tasks. Children selected 1 of 2
      arguments to persuade a puppet to do something (e.g., pet a dog) after hearing
      the puppet's belief (e.g., "I think puppies bite"). Across 2 studies, 132
      children (ages 3-7 years) engaged in these persuasion tasks and in false-belief
      reasoning tasks, presented in puppet and story formats. Belief-relevant argument
      selection increased with age, as did appropriate reasoning about false beliefs,
      and occurred more in puppet than story tasks. Results suggest that improvements
      in belief reasoning in early childhood may be reflected in social interactions
      such as persuasion.

PMID- 17201513
TI  - What counts as by? Young children's use of relative distance to judge nearbyness.
AB  - The authors investigated how 3- and 4-year-old children and adults use relative
      distance to judge nearbyness. Participants judged whether several blocks were by
      a landmark. The absolute and relative distance of the blocks from the landmark
      varied. In Experiment 1, judgments of nearbyness decreased as the distance from
      the landmark increased, particularly for 4-year-olds and adults. In Experiment 2,
      4-year-olds and adults were more likely to judge objects at an intermediate
      distance as by the landmark when intervening objects were absent than when
      intervening objects were present. In Experiment 3, participants of all ages were
      more likely to judge objects at a short distance as by the landmark when
      intervening objects were absent. Reliance on relative distance to judge
      nearbyness becomes more systematic and applicable to larger spatial extents
      across development.

PMID- 17201514
TI  - Older but wilier: In-group accountability and the development of subjective group
      dynamics.
AB  - To test social and cognitive variables that may affect the development of
      subjective group dynamics, the authors had 224 children between the ages of 5 and
      12 years evaluate an in-group and an out-group and normative and deviant in-group
      members under conditions of high or low accountability to in-group peers. In
      group bias and relative favorability to normative versus deviant in-group members
      (differential evaluation) increased when children were accountable to peers and
      as a function of perceptions of peer group acceptance of these members
      (differential inclusion). These effects were significantly larger among older
      children. Multiple classification ability was unrelated to judgments of group
      members. This study shows that the development of subjective group dynamics
      involves an increase in sensitivity to the normative aspects of the intergroup
      context.

PMID- 17201515
TI  - Knowing who dunnit: Infants identify the causal agent in an unseen causal
      interaction.
AB  - Preverbal infants can represent the causal structure of events, including
      distinguishing the agentive and receptive roles and categorizing entities
      according to stable causal dispositions. This study investigated how infants
      combine these 2 kinds of causal inference. In Experiments 1 and 2, 9.5-month-olds
      used the position of a human hand or a novel puppet (causal agents), but not a
      toy train (an inert object), to predict the subsequent motion of a beanbag.
      Conversely, in Experiment 3, 10- and 7-month-olds used the motion of the beanbag
      to infer the position of a hand but not of a toy block. These data suggest that
      preverbal infants expect a causal agent as the source of motion of an inert
      object.

PMID- 17201516
TI  - The role of domain-specific practice, handedness, and starting age in chess.
AB  - The respective roles of the environment and innate talent have been a recurrent
      question for research into expertise. The authors investigated markers of talent,
      environment, and critical period for the acquisition of expert performance in
      chess. Argentinian chess players (N = 104), ranging from weak amateurs to
      grandmasters, completed a questionnaire measuring variables including individual
      and group practice, starting age, and handedness. The study reaffirms the
      importance of practice for reaching high levels of performance, but it also
      indicates a large variability: The slower player needed 8 times as much practice
      to reach master level than the faster player. Additional results show a
      correlation between skill and starting age and indicate that players are more
      likely to be mixed-handed than individuals in the general population; however,
      there was no correlation between handedness and skill within the sample of chess
      players. Together, these results suggest that practice is a necessary but not
      sufficient condition for the acquisition of expertise, that some additional
      factors may differentiate chessplayers and nonchessplayers, and that starting age
      of practice is important.

PMID- 17201517
TI  - Effects of a teen pregnancy prevention program on teens' attitudes toward
      sexuality: A latent trait modeling approach.
AB  - The purpose of this study was to examine the effects of program interventions in
      a school-based teen pregnancy program on hypothesized constructs underlying
      teens' attitudes toward sexuality. An important task related to this purpose was
      the validation of the constructs and their stability from pre- to
      postintervention measures. Data from 1,136 middle grade students were obtained
      from an earlier evaluation of an abstinence-based teen pregnancy prevention
      program (S. Weed, I. Ericksen, G. Grant, & A. Lewis, 2002). Latent trait
      structural equation modeling was used to evaluate the impact of the intervention
      program on changes in constructs of teens' attitudes toward sexuality. Gender was
      also taken into consideration. This investigation provides credible evidence that
      both 1st- and 2nd-order constructs related to measures of teens' attitudes toward
      risky sexual behavior are sufficiently stable and sensitive to detect program
      effects.

PMID- 17201518
TI  - Conditional probability versus spatial contiguity in causal learning:
      Preschoolers use new contingency evidence to overcome prior spatial assumptions.
AB  - This study examines preschoolers' causal assumptions about spatial contiguity and
      how these assumptions interact with new evidence in the form of conditional
      probabilities. Preschoolers saw a toy that activated in the presence of certain
      objects. Children were shown evidence for the toy's activation rule in the form
      of patterns of probability: The toy was more likely to activate either when
      objects made contact with its surface (on condition) or when objects were several
      inches above its surface (over condition). In Experiment 1, 61 three-year-olds
      saw a deterministic activation rule. In Experiments 2 and 3, 48 four-year-olds
      saw an activation rule that was probabilistic. In Experiment 4, 30 four-year-olds
      saw a screening-off pattern of activation. In all 4 experiments, children used
      new evidence in the form of patterns of probability to make accurate causal
      inferences, even in the face of conflicting prior beliefs about spatial
      contiguity. However, children were more likely to make correct inferences when
      causes were spatially contiguous, particularly when faced with ambiguous
      evidence.

PMID- 17201519
TI  - Staying in or moving away from structured activities: Explanations involving
      parents and peers.
AB  - Adolescent participation in structured activities, meaning those with adult
      leaders, regular meetings, and skill-building activities, is related to good
      adjustment. Participation in unstructured, unsupervised, peer-oriented activities
      is related to poor adjustment. Structured activity participation is high in early
      adolescence and then declines, raising the question of why youths leave
      structured activities. The authors examined explanations involving parents and
      peers. They used longitudinal data from 861 youths (ages 13-17 years). Results
      showed that, compared with youths who stayed in structured activities, those who
      switched to hanging out on the streets were less likely to have peers in
      structured activities and had less positive feelings about the home context and
      more negative interactions with parents. In addition, delinquency predicted
      switching to hanging out in the streets and never joining structured activities
      in the first place. The results concerning parents support a theoretical
      explanation of how parents might unintentionally affect youths' leisure choices.
      Furthermore, the authors found some indications that positive feelings at home
      might protect youths who switch from structured activities to hanging out on the
      streets from increases in delinquency.

PMID- 17201520
TI  - Effortful control among low-income preschoolers in three cities: Stability,
      change, and individual differences.
AB  - Existing developmental models of effortful control focus more on the roles of
      child characteristics and parenting and focus less on the contributions of
      poverty-related stressors to individual differences in children's self-regulatory
      competence. Using a representative sample of low-income, predominantly African
      American and Latino children (n = 439), the author examined effortful control at
      ages 2-4 and again 16 months later. Delayed gratification showed moderate
      stability and improvement over time. Risk factors were associated with individual
      differences in these developmental patterns, net of child age, gender,
      temperament, and child-mother connectedness. Low birth weight compromised
      preschoolers' delayed gratification and executive control. Exposure to more
      sociodemographic and residential stressors jeopardized children's executive
      control but did not jeopardize delayed gratification.

PMID- 17201521
TI  - Children's fearfulness as a moderator of parenting in early socialization: Two
      longitudinal studies.
AB  - Findings from 2 longitudinal studies replicate and considerably extend past work
      on child temperament as a moderating link between parenting and successful
      socialization outcomes. In Study 1 (N = 106 mothers and children), child
      fearfulness, mother-child positive relationship, and maternal power assertion
      were assessed at 22 and 33 months; the outcome--children's moral self--was
      assessed at 56 months. In Study 2 (N = 102 mothers, fathers, and children), child
      fearfulness and parent-child positive relationship were assessed at 7 and 15
      months; parents' power assertion was assessed at 15 months. The outcomes were
      children's receptive, willing stance toward the parent at 25 months, and rule
      compatible conduct without supervision at 38 months. Child fearfulness
      significantly moderated the impact of parenting: In both studies, for relatively
      fearless children, mother-child positive relationship predicted future successful
      socialization outcomes in mother-child dyads. There was no analogous moderation
      effect in father-child dyads in Study 2. For relatively fearful children,
      fathers' power assertion in Study 2 predicted poor socialization outcomes. All
      Temperament x Parenting interactions appeared limited to measures obtained in the
      2nd year.

PMID- 17201523
TI  - Age-related changes in odor discrimination.
AB  - Odor naming and recognition memory are poorer in children than in adults. This
      study explored whether such differences might result from poorer discriminative
      ability. Experiment 1 used an oddity test of discrimination with familiar odors
      on 6-year-olds, 11-year-olds, and adults. Six-year-olds were significantly poorer
      at discrimination relative to 11-year-olds and adults, who did not differ.
      Experiment 2 used the same procedure but with hard-to-name visual stimuli and
      compared only 6-year-olds with adults (as with the remaining experiments in this
      study). There was no difference in performance between these groups. Experiment 3
      used the same procedure as Experiment 1 but with less familiar odors. Six-year
      olds were significantly poorer at discrimination than adults. In Experiment 4 the
      researchers controlled for verbal labeling by using an articulatory suppression
      task, with the same basic procedure as in Experiment 1. Six-year-old performance
      was the same as for Experiment 1 and significantly poorer than that of adults.
      Impoverished olfactory discrimination may underpin performance deficits
      previously observed in children. These all may result from their lesser
      experience with odors, relative to adults.

PMID- 17201522
TI  - The development of infant discrimination of affect in multimodal and unimodal
      stimulation: The role of intersensory redundancy.
AB  - This research examined the developmental course of infants' ability to perceive
      affect in bimodal (audiovisual) and unimodal (auditory and visual) displays of a
      woman speaking. According to the intersensory redundancy hypothesis (L. E.
      Bahrick, R. Lickliter, & R. Flom, 2004), detection of amodal properties is
      facilitated in multimodal stimulation and attenuated in unimodal stimulation.
      Later in development, however, attention becomes more flexible, and amodal
      properties can be perceived in both multimodal and unimodal stimulation. The
      authors tested these predictions by assessing 3-, 4-, 5-, and 7-month-olds'
      discrimination of affect. Results demonstrated that in bimodal stimulation,
      discrimination of affect emerged by 4 months and remained stable across age.
      However, in unimodal stimulation, detection of affect emerged gradually, with
      sensitivity to auditory stimulation emerging at 5 months and visual stimulation
      at 7 months. Further temporal synchrony between faces and voices was necessary
      for younger infants' discrimination of affect. Across development, infants first
      perceive affect in multimodal stimulation through detecting amodal properties,
      and later their perception of affect is extended to unimodal auditory and visual
      stimulation. Implications for social development, including joint attention and
      social referencing, are considered.

PMID- 17201524
TI  - Gender identity and adjustment in black, Hispanic, and white preadolescents.
AB  - The generality of S. K. Egan and D. G. Perry's (2001) model of gender identity
      and adjustment was evaluated by examining associations between gender identity
      (felt gender typicality, felt gender contentedness, and felt pressure for gender
      conformity) and social adjustment in 863 White, Black, and Hispanic 5th graders
      (mean age = 11.1 years). Relations between gender identity and adjustment varied
      across ethnic/racial groups, indicating that S. K. Egan and D. G. Perry's model
      requires amendment. It is suggested that the implications of gender identity for
      adjustment depend on the particular meanings that a child attaches to gender
      (e.g., the specific attributes the child regards as desirable for each sex);
      these meanings may vary across and within ethnic/racial groups. Cross
      ethnic/racial investigation can aid theory building by pointing to constructs
      that are neglected in research with a single ethnic/racial group but that are
      crucial components of basic developmental processes.

PMID- 17201525
TI  - APOE genotype and cognitive functioning in a large age-stratified population
      sample.
AB  - There is evidence that the cognitive effects of Alzheimer's disease can be seen
      decades before disease diagnosis. If this is the case, then the apolipoprotein E
      (APOE) *E4 allele might be expected to have effects on cognitive functioning
      earlier in the life span. To assess such effects, the authors examined data on
      the *E4 allele and cognitive functioning from a population sample of 6,560
      Caucasians covering the age groups of 20-24, 40-44, and 60-64 years. Participants
      were assessed on tests of episodic memory, working memory, mental speed, reaction
      time, and reading vocabulary. Although performance on all tests except reading
      vocabulary declined across age groups, there was no effect of the APOE *E4 allele
      at any age. These results indicate that APOE *E4 does not have preclinical
      effects early in the life span on these cognitive functions. Cognitive aging
      effects between the ages of 20 and 64 years must not be due to preclinical
      Alzheimer's disease.

PMID- 17201526
TI  - Reversal of the concreteness effect for verbs in patients with semantic dementia.
AB  - The authors assessed comprehension of carefully matched classes of words,
      manipulating grammatical subcategory (noun and verb) and semantic (concrete and
      abstract) characteristics for participants with semantic dementia (SD) or
      probable Alzheimer's disease (AD). Participants selected the best of four words
      that matched a verbal description. Participants with AD or SD were significantly
      impaired with verbs compared with nouns. Moreover, participants with SD showed
      significantly greater difficulty with motion verbs compared to cognition verbs.
      The authors argue that two factors contribute to the difficulty with motion verbs
      for patients with SD. First, the verb semantic network is very poorly organized
      relative to the noun semantic network, leaving verbs more vulnerable to a
      progressive neurodegenerative disease. Second, visual feature knowledge is
      degraded in patients with SD because of the anatomic distribution of the disease
      in visual association cortex, causing relatively greater difficulty for concrete
      verbs compared to abstract verbs.

PMID- 17201527
TI  - Disparate letter and semantic category fluency deficits in autopsy-confirmed
      frontotemporal dementia and Alzheimer's disease.
AB  - Patients with autopsy-confirmed frontotemporal dementia (FTD; n = 16) and
      Alzheimer's disease (AD; n = 32) were compared on first-letter and semantic
      category fluency tasks. Despite being matched on age, education, and dementia
      severity, FTD patients performed worse overall and showed similar impairment in
      letter and semantic category fluency, whereas AD patients showed greater
      impairment in semantic category than letter fluency. A measure of the disparity
      between letter and semantic category fluency (the semantic index) was effective
      in differentiating FTD from AD patients, and this disparity increased with
      increasing severity of dementia. These unique patterns of letter and semantic
      category fluency deficits may be indicative of differences in the relative
      contribution of frontal-lobe-mediated retrieval deficits and temporal-lobe
      mediated semantic deficits in FTD and AD.

PMID- 17201529
TI  - The latent structure of attention-deficit/hyperactivity disorder in a clinic
      referred sample.
AB  - The question of whether attention-deficit/hyperactivity disorder (ADHD)
      represents a continuum of attentional and executive dysfunction or a natural
      category has yet to be extensively investigated. Subjective report and
      neuropsychological data from 437 individuals referred for neuropsychological
      evaluation were analyzed using latent class and taxometric analyses (mean above
      minus below a cut [MAMBAC], maximum eigenvalue [MAXEIG], and latent mode
      [LMODE]). Results indicated no significant evidence for a taxonic representation
      of ADHD across multiple procedures and indicator sets. Similarly, there was no
      evidence that ADHD subtypes represent a qualitative distinction. These findings
      may suggest that current diagnostic conceptualizations are inadequate for
      accurately identifying and characterizing individuals with problems related to
      attention and executive dysfunction. Alternatively, the null findings may have
      resulted from inadequate indicator selection. A dimensional model may better
      facilitate accurate identification of individuals at risk for functional
      impairment.

PMID- 17201528
TI  - Early cognitive deficits in Swedish gene carriers of Huntington's disease.
AB  - The primary focus of this study was to examine whether there is early
      neuropsychological impairment in presymptomatic Huntington's disease (HD). A
      broad neuropsychological assessment battery was administered to 24 asymptomatic
      gene carriers (HD+) and 31 noncarriers (HD-). The gene carriers revealed inferior
      cognitive functioning as compared with the noncarriers in memory and executive
      functions. When the gene carriers were assigned to 2 groups based on predicted
      years to onset (with 15 and over being HD+ late and under 15 being HD+ near), the
      HD+ near group performed significantly worse than the HD+ late group in all
      domains but ability to shift conceptually and visuospatial memory. Results
      suggest that early cognitive deficits are detectable prior to motor symptoms,
      first in memory functions and then in executive functions and perceptual motor
      speed.

PMID- 17201530
TI  - Visual information processing in high-functioning individuals with autism
      spectrum disorders and their parents.
AB  - The authors assessed visual information processing in high-functioning
      individuals with pervasive developmental disorders (PDD) and their parents. The
      authors used tasks for contrast sensitivity, motion, and form perception to test
      visual processing occurring relatively early and late in the magnocellular-dorsal
      and parvocellular-ventral pathways. No deficits were found in contrast
      sensitivity for low or high spatial frequencies or for motion or form perception
      between individuals with PDD in comparison with a matched control group.
      Individuals with PDD performed equally with or better than controls on motion
      detection tasks. In addition, the authors did not find differences on any of the
      tasks between parents of the PDD group and matched control parents. These results
      indicate that high-functioning individuals with PDD and their parents are able to
      process visual stimuli that rely on early or late processing in the magnocellular
      dorsal and parvocellular-ventral pathways as well as controls.

PMID- 17201531
TI  - Quantitative electroencephalographic profiles for children with autistic spectrum
      disorder.
AB  - The present study examined quantitative electroencephalographic (QEEG) profile
      for children with autistic spectrum disorder (ASD). Five-minute QEEG data were
      obtained from 90 normal controls (NCs) and 66 children with ASD. Spectrum
      analyses revealed that ASD children showed significantly less relative alpha and
      more relative delta than NC. Specifically, 26% of ASD children and 2% of NCs
      showed 1.5 SDs of relative alpha below the normative mean. Children with this
      QEEG profile had 17 times the risk of having ASD than those without such a
      profile. Sensitivity and specificity of relative alpha were 91% and 73%,
      respectively. Split-half cross-validation yielded a sensitivity of 76%.

PMID- 17201532
TI  - Interhemispheric integration in psychopathic offenders.
AB  - The goal of the present study was to determine whether a reduced capacity for
      interhemispheric integration can explain the attention deficits seen in
      psychopathic individuals under conditions that place substantial demands on left
      hemisphere-specific resources. The present study examined the performance of 54
      incarcerated psychopathic and nonpsychopathic male offenders on a same-different
      global-local paradigm that permits manipulation of both the magnitude of
      processing demands and the demand for interhemispheric coordination. Prior
      studies with similar paradigms have demonstrated that the cerebral hemispheres
      can function more efficiently as relatively independent processors on simple
      tasks, whereas communication between the hemispheres improves performance when
      processing demands are heavy. Analyses indicated that psychopathic offenders are
      not deficient in interhemispheric integration but provided additional evidence
      consistent with the left hemisphere activation hypothesis of psychopathy.

PMID- 17201533
TI  - Impaired orienting of attention in left unilateral neglect: a componential
      analysis.
AB  - Twenty-six patients suffering from damage to the right side of the brain, 19 of
      whom exhibited signs of left neglect, as well as 32 matched controls, ran 3
      spatial cuing tasks. Patients were also tested with 2 cancellation tests, a line
      bisection test, the copy of a complex drawing, and a visual extinction procedure.
      Results first showed correlations between extinction and cancellation tests
      performance on one hand, and between line bisection and copy on the other hand.
      Second, results demonstrated that an engagement deficit toward contralesional
      targets appeared to be the most striking feature of neglect, and the engagement
      score was correlated with the cancellation score and extinction. Most patients
      with neglect also presented a deficit in disengagement, a deficit of inhibition
      of return, and probably a deficit of alertness. Deficits in engagement and in
      disengagement, as well as poor scores in cancellation tests, seemed to be related
      with posterior cortical and subcortical lesions. Most important, even if an
      endogenous deficit (frequently related with a thalamic lesion) could aggravate
      the neglect behavior, neglect syndrome was mainly explained by a deficit of
      exogenous attention.

PMID- 17201534
TI  - Visual memory for shapes in deaf signers and nonsigners and in hearing signers
      and nonsigners: atypical lateralization and enhancement.
AB  - Deaf and hearing individuals who either used sign language (signers) or not
      (nonsigners) were tested on visual memory for objects and shapes that were
      difficult to describe verbally with a same/different matching paradigm. The use
      of 4 groups was designed to permit a separation of effects related to sign
      language use (signers vs. nonsigners) and effects related to auditory deprivation
      (deaf vs. hearing). Forty deaf native signers and nonsigners and 51 hearing
      signers and nonsigners participated in the study. Signing individuals (both deaf
      and hearing) were more accurate than nonsigning individuals (deaf and hearing) at
      memorizing shapes. For the shape memory task but not the object task, deaf
      signers and nonsigners displayed right hemisphere (RH) advantage over the left
      hemisphere (LH). Conversely, both hearing groups displayed a memory advantage for
      shapes in the LH over the RH. Results indicate that enhanced memory performance
      for shapes in signers (deaf and hearing) stems from the visual skills acquired
      through sign language use and that deafness, irrespective of language background,
      leads to the use of a visually based strategy for memory of difficult-to-describe
      items.

PMID- 17201535
TI  - The semantic and episodic subcomponents of famous person knowledge: dissociation
      in healthy subjects.
AB  - Fifty-two subjects between ages 40 and 79 years were administered a questionnaire
      assessing their ability to recall semantic information about famous people from 4
      different decades and to recollect its episodic source of acquisition together
      with autonoetic consciousness via the remember-know paradigm. In addition, they
      underwent a battery of standardized neuropsychological tests to assess episodic
      and semantic memory and executive functions. The analyses of age reveal
      differences for the episodic source score but no differences between age groups
      for the semantic scores within each decade. Regardless of the age of people, the
      analyses also show that semantic memory subcomponents of the famous person test
      are highly associated with each other as well as with the source component. The
      recall of semantic information on the famous person test relies on participants'
      semantic abilities, whereas the recall of its episodic source depends on their
      executive functions. The present findings confirm the existence of an episodic
      semantic distinction in knowledge about famous people. They provide further
      evidence that personal source and semantic information are at once distinct and
      highly interactive within the framework of remote memory.

PMID- 17201536
TI  - Serum uric acid and cognitive function in community-dwelling older adults.
AB  - Among possible markers of age-related cognitive decline, uric acid (UA) is
      controversial because it has antioxidant properties but is increased in diseases
      that often lead to cognitive impairment. In this study of 96 elderly adults,
      participants with mildly elevated (but normal) serum UA were 2.7 to 5.9 times
      more likely to score in the lowest quartile of the sample on measures of
      processing speed, verbal memory, and working memory. Even after controlling for
      age, sex, race, education, diabetes, hypertension, smoking, and alcohol abuse,
      the multivariate-adjusted odds of poor verbal memory and working memory remained
      significant (ps < .05). Despite its antioxidant properties, these findings
      suggest that even mild elevations of UA might increase the risk of cognitive
      decline among older adults.

PMID- 17201537
TI  - Extreme right-handedness, older brothers, and sexual orientation in men.
AB  - Two of the most consistent correlates of sexual orientation in men are handedness
      and fraternal birth order (i.e., number of older brothers). In the present study,
      the relationship among handedness, older brothers, and sexual orientation was
      studied in 4 samples of heterosexual and gay or bisexual men (N = 944). Unlike
      previous studies, which have only observed an increased rate of non-right
      handedness in gay or bisexual men relative to heterosexual men, an elevated rate
      of extreme right-handedness was found in gay or bisexual men relative to
      heterosexual men. The results also demonstrated that older brothers moderate the
      relationship between handedness and sexual orientation. Specifically, older
      brothers increase the odds of being gay or bisexual in moderate right-handers
      only; in both non-right-handers and extreme right-handers, older brothers do not
      affect (or decrease) the odds of being gay or bisexual. The results have
      implications for an early neurodevelopmental origin to sexual orientation in men.

PMID- 17201538
TI  - "Express yourself": culture and the effect of self-expression on choice.
AB  - Whereas self-expression is valued in the United States, it is not privileged with
      such a cultural emphasis in East Asia. Four studies demonstrate the psychological
      implications of this cultural difference. Studies 1 and 2 found that European
      Americans value self-expression more than East Asians/East Asian Americans.
      Studies 3 and 4 examined the roles of expression in preference judgments. In
      Study 3, the expression of choice led European Americans but not East Asian
      Americans to be more invested in what they chose. Study 4 examined the connection
      between the value of expression and the effect of choice expression and showed
      that European Americans place greater emphasis on self-expression than East Asian
      Americans, and this difference explained the cultural difference in Study 3. This
      research highlights the importance of the cultural meanings of self-expression
      and the moderating role of cultural beliefs on the psychological effect of self
      expression.

PMID- 17201539
TI  - Cancer and the threat of death: the cognitive dynamics of death-thought
      suppression and its impact on behavioral health intentions.
AB  - Five studies examined the cognitive association between thoughts of cancer and
      thoughts of death and their implication for screening intentions. Study 1 found
      that explicit contemplation of cancer did not increase death-thought
      accessibility. In support of the hypothesis that this reflects suppression of
      death-related thoughts, Study 2 found that individuals who thought about cancer
      exhibited elevated death-thought accessibility under high cognitive load, and
      Study 3 demonstrated that subliminal primes of the word cancer led to increased
      death-thought accessibility. Study 4 revealed lower levels of death-thought
      accessibility when perceived vulnerability to cancer was high, once again
      suggesting suppression of death-related thoughts in response to conscious threats
      associated with cancer. Study 5 extended the analysis by finding that after
      cancer salience, high cognitive load, which presumably disrupts suppression of
      the association between cancer and death, decreased cancer-related self-exam
      intentions. Theoretical and practical implications for understanding terror
      management, priming and suppression, and responses to cancer are discussed.

PMID- 17201540
TI  - Unpacking attitude certainty: attitude clarity and attitude correctness.
AB  - Attitude certainty has been the subject of considerable attention in the
      attitudes and persuasion literature. The present research identifies 2 aspects of
      attitude certainty and provides evidence for the distinctness of the constructs.
      Specifically, it is proposed that attitude certainty can be conceptualized, and
      empirically separated, in terms of attitude clarity (the subjective sense that
      one knows what one's attitude is) and attitude correctness (the subjective sense
      that one's attitude is correct or valid). Experiment 1 uses factor analysis and
      correlational data to provide evidence for viewing attitude clarity and attitude
      correctness as separate constructs. Experiments 2 and 3 demonstrate that attitude
      clarity and attitude correctness can have distinct antecedents (repeated
      expression and consensus feedback, respectively). Experiment 4 reveals that these
      constructs each play an independent role in persuasion and resistance situations.
      As clarity and correctness increase, attitudes become more resistant to
      counterattitudinal persuasive messages. These findings are discussed in relation
      to the existing attitude strength literature.

PMID- 17201541
TI  - Does social exclusion motivate interpersonal reconnection? Resolving the
      "porcupine problem".
AB  - Evidence from 6 experiments supports the social reconnection hypothesis, which
      posits that the experience of social exclusion increases the motivation to forge
      social bonds with new sources of potential affiliation. Threat of social
      exclusion led participants to express greater interest in making new friends, to
      increase their desire to work with others, to form more positive impressions of
      novel social targets, and to assign greater rewards to new interaction partners.
      Findings also suggest potential boundary conditions to the social reconnection
      hypothesis. Excluded individuals did not seem to seek reconnection with the
      specific perpetrators of exclusion or with novel partners with whom no face-to
      face interaction was anticipated. Furthermore, fear of negative evaluation
      moderated responses to exclusion such that participants low in fear of negative
      evaluation responded to new interaction partners in an affiliative fashion,
      whereas participants high in fear of negative evaluation did not.

PMID- 17201542
TI  - Social exclusion decreases prosocial behavior.
AB  - In 7 experiments, the authors manipulated social exclusion by telling people that
      they would end up alone later in life or that other participants had rejected
      them. Social exclusion caused a substantial reduction in prosocial behavior.
      Socially excluded people donated less money to a student fund, were unwilling to
      volunteer for further lab experiments, were less helpful after a mishap, and
      cooperated less in a mixed-motive game with another student. The results did not
      vary by cost to the self or by recipient of the help, and results remained
      significant when the experimenter was unaware of condition. The effect was
      mediated by feelings of empathy for another person but was not mediated by mood,
      state self-esteem, belongingness, trust, control, or self-awareness. The
      implication is that rejection temporarily interferes with emotional responses,
      thereby impairing the capacity for empathic understanding of others, and as a
      result, any inclination to help or cooperate with them is undermined.

PMID- 17201543
TI  - Authoritarian dynamics and unethical decision making: high social dominance
      orientation leaders and high right-wing authoritarianism followers.
AB  - When dilemmas require trade-offs between profits and ethics, do leaders high in
      social dominance orientation (SDO) and followers high in right-wing
      authoritarianism (RWA) make decisions that are more unethical than those made by
      others? This issue was explored in 4 studies with female participants performing
      managerial role-playing tasks. First, dyads comprising a person who was either
      low or high in SDO and a person who was either low or high in RWA negotiated for
      a leadership position. People high in SDO were more likely to obtain leader
      positions than to obtain follower positions. No other effects were significant.
      Second, leaders high in SDO partnered with an agreeable (confederate) follower
      made decisions that were more unethical than those of leaders low in SDO. Third,
      followers high in RWA were more acquiescent to and supportive of an unethical
      (confederate) leader than were followers low in RWA. Fourth, high SDO leader-high
      RWA follower dyads made decisions that were more unethical than those made in
      role-reversed dyads because leaders had more influence. Implications of these
      results for conceptualizing SDO, RWA, and authoritarian dynamics are discussed.

PMID- 17201544
TI  - A question of belonging: race, social fit, and achievement.
AB  - Stigmatization can give rise to belonging uncertainty. In this state, people are
      sensitive to information diagnostic of the quality of their social connections.
      Two experiments tested how belonging uncertainty undermines the motivation and
      achievement of people whose group is negatively characterized in academic
      settings. In Experiment 1, students were led to believe that they might have few
      friends in an intellectual domain. Whereas White students were unaffected, Black
      students (stigmatized in academics) displayed a drop in their sense of belonging
      and potential. In Experiment 2, an intervention that mitigated doubts about
      social belonging in college raised the academic achievement (e.g., college
      grades) of Black students but not of White students. Implications for theories of
      achievement motivation and intervention are discussed.

PMID- 17201545
TI  - Less is more: the lure of ambiguity, or why familiarity breeds contempt.
AB  - The present research shows that although people believe that learning more about
      others leads to greater liking, more information about others leads, on average,
      to less liking. Thus, ambiguity--lacking information about another--leads to
      liking, whereas familiarity--acquiring more information--can breed contempt. This
      "less is more" effect is due to the cascading nature of dissimilarity: Once
      evidence of dissimilarity is encountered, subsequent information is more likely
      to be interpreted as further evidence of dissimilarity, leading to decreased
      liking. The authors document the negative relationship between knowledge and
      liking in laboratory studies and with pre- and postdate data from online daters,
      while showing the mediating role of dissimilarity.

PMID- 17201546
TI  - On models and vases: body dissatisfaction and proneness to social comparison
      effects.
AB  - When and why do media-portrayed physically attractive women affect perceivers'
      self-evaluations? In 6 studies, the authors showed that whether such images
      affect self-evaluations depends jointly on target features and perceiver
      features. In Study 1, exposure to a physically attractive target, compared with
      exposure to an equally attractive model, lowered women's self-evaluations. Study
      2 showed that body-dissatisfied women, to a greater extent than body-satisfied
      women, report that they compare their bodies with other women's bodies. In Study
      3, body-dissatisfied women, but not body-satisfied women, were affected by both
      attractive models and nonmodels. Furthermore, in Study 4, it was body
      dissatisfied women, rather than body-satisfied women, who evaluated themselves
      negatively after exposure to a thin (versus a fat) vase. The authors replicated
      this result in Study 5 by manipulating, instead of measuring, body
      dissatisfaction. Finally, Study 6 results suggested that body dissatisfaction
      increases proneness to social comparison effects because body dissatisfaction
      increases self-activation.

PMID- 17201547
TI  - What do you learn about someone over time? The relationship between length of
      acquaintance and consensus and self-other agreement in judgments of personality.
AB  - Theory and research examining length of acquaintance and consensus among
      personality judgments have predominantly examined each dimension of personality
      separately. In L. J. Cronbach's (1955) terminology, this trait-centered approach
      combines consensus on elevation, differential elevation, and differential
      accuracy in personality judgments. The current article extends D. A. Kenny's
      (1991, 1994) weighted average model (WAM)--a theoretical model of the factors
      that influence agreement among personality judgments--to separate out two of
      Cronbach's components of consensus: stereotype accuracy and differential
      accuracy. Consistent with the predictions based on the WAM, as length of
      acquaintance increased, self-other agreement and consensus differential accuracy
      increased, stereotype accuracy decreased, and trait-level or raw profile
      correlations generally remained unchanged. Discussion focuses on the conditions
      under which a relationship between length of acquaintance and consensus and self
      other agreement among personality evaluations emerges and how impressions change
      over time.

PMID- 17201548
TI  - Parental personality as an inner resource that moderates the impact of ecological
      adversity on parenting.
AB  - Parents' personality was examined as a moderator of the impact of demographic
      risk on parenting in a longitudinal study (N=102 families). Parents' personality
      and demographic risk (i.e., education level, age, family income, and family size)
      were assessed when children were infants, and parents' power assertion, warmth,
      and positive affect were observed in naturalistic interactions 2.5 years later.
      Parents' personality moderated the adverse impact of demographic risk on
      parenting. For parents who had memories of unstable and unhappy childhood
      experiences and who reported low conventionality, higher risk was linked to more
      power assertion, but there was no such link for those parents who recalled happy
      childhood experiences and who embraced conventions. For both parents who lacked a
      sense of optimism and social trust, and for fathers who reported low
      conventionality, higher risk was linked to less affectively positive parenting,
      but there was no such link for parents who were optimistic and trusting or for
      fathers who were conventional. Higher risk was linked to more power assertion,
      but only for mothers low in Extraversion and for fathers high in Neuroticism.

PMID- 17201549
TI  - Changes in women's mate preferences across the ovulatory cycle.
AB  - Previous research has shown that women's mate preferences change across the
      ovulatory cycle in a number of ways. The leading explanation for these changes-
      the good genes hypothesis--predicts that women should prefer presumed markers of
      genetic benefits ("good genes") most strongly when they are fertile and
      evaluating men as possible short-term mates. Research testing this hypothesis has
      almost exclusively examined preferences for purported markers of good genes.
      Little is known about how preferences for men who display traits valued in long
      term, investing mates (e.g., warmth and faithfulness) change across the cycle.
      The authors had women at different points in their ovulatory cycle rate
      videotapes of men in terms of how attractive they found each man as a short-term
      and long-term mate. The authors then examined how women's preferences for traits
      typically valued in long-term and/or short-term mates varied according to women's
      fertility status. The results supported the good genes hypothesis. Implications
      of these findings for models of human mating are discussed.

PMID- 17201551
TI  - Conflict and criterion setting in recognition memory.
AB  - Recognition memory requires both retrieval processes and control processes such
      as criterion setting. Decision criteria were manipulated by offering different
      payoffs for correct "old" versus "new" responses. Criterion setting influenced
      the following late-occurring (1,000+ ms), conflict-sensitive event-related brain
      potential (ERP) components: the stimulus-locked late posterior negativity (LPN)
      and the response-locked error-related negativity (ERN). The LPN-ERN were most
      negative to hits under conservative payoff conditions involving conflict between
      the correct old response and the payoff for new responses. This same conservative
      hit condition was most frequently associated with response reversals when fast
      initial judgments were followed by slower judgments. Postresponse ERP activity
      may index conflict-sensitive processes underlying postretrieval cognitive control
      mechanisms involved with assessing responses to current items and updating
      response criteria on later trials.

PMID- 17201552
TI  - The mirror effect and mixture signal detection theory.
AB  - The mirror effect for word frequency refers to the finding that low-frequency
      words have higher hit rates and lower false alarm rates than high-frequency
      words. This result is typically interpreted in terms of conventional signal
      detection theory (SDT), in which case it indicates that the order of the
      underlying old item distributions mirrors the order of the new item
      distributions. However, when viewed in terms of a mixture version of SDT, the
      order of hits and false alarms does not necessarily imply the same order in the
      underlying distributions because of possible effects of mixing. A reversal in
      underlying distributions did not appear for fits of mixture SDT models to data
      from 4 experiments.

PMID- 17201553
TI  - Psychometric intelligence dissociates implicit and explicit learning.
AB  - The hypothesis that performance on implicit learning tasks is unrelated to
      psychometric intelligence was examined in a sample of 605 German pupils.
      Performance in artificial grammar learning, process control, and serial learning
      did not correlate with various measures of intelligence when participants were
      given standard implicit instructions. Under an explicit rule discovery
      instruction, however, a significant relationship between performance on the
      learning tasks and intelligence appeared. This finding provides support for
      Reber's hypothesis that implicit learning, in contrast to explicit learning, is
      independent of intelligence, and confirms thereby the distinction between the 2
      modes of learning. However, because there were virtually no correlations among
      the 3 learning tasks, the assumption of a unitary ability of implicit learning
      was not supported.

PMID- 17201554
TI  - Event-related potential indicators of text integration across sentence
      boundaries.
AB  - An event-related potentials (ERPs) study examined word-to-text integration
      processes across sentence boundaries. In a two-sentence passage, the
      accessibility of a referent for the first content word of the second sentence
      (the target word) was varied by the wording of the first sentence in one of the
      following ways: lexically (explicitly using a form of the target word);
      conceptually (using a paraphrase of the target word), and situationally
      (encouraging an inference concerning the referent of the target word). A baseline
      condition had no coreference between the two sentences. ERP results on the target
      word indicated multiple effects related to word identification and word-to
      referent mapping processes. Both the explicit and paraphrase conditions, but not
      the inference condition, showed a reduced N400 relative to the baseline
      condition, consistent with immediate integration by lexico-semantic processes. A
      300-ms effect (P300) was found in the paraphrase condition. The results were
      consistent with an immediate integration hypothesis and furthermore
      differentiated a lexical (N200), a conceptual (P300), and a situational (N400)
      component for this integration. The conceptual basis appears not to extend to
      predictive inferences.

PMID- 17201555
TI  - Associative symmetry versus independent associations in the memory for object
      location associations.
AB  - The formation of associations between objects and locations is a vital aspect of
      episodic memory. More specifically, remembering the location where one
      experienced an object and, vice versa, the object one encountered at a specific
      location are both important elements for the memory of an event. Whether episodic
      associations are holistic representations of individual components or whether
      there are unidirectional, separately modifiable connections between them has been
      investigated nearly exclusively using verbal stimuli. A preliminary conclusion
      concerning this controversy is that verbal associations are, at least, highly
      correlated (M. J. Kahana, 2002). This theoretical debate, which in the past has
      undergone a major empirical effort, is still of relevance for the concurrent
      global matching models of associative memory (S. E. Clark & S. D. Gronlund,
      1996). The authors used variations of a novel object-location learning paradigm
      to complement the accumulated evidence regarding the nature of episodic
      associations.

PMID- 17201556
TI  - A response-time approach to comparing generalized rational and take-the-best
      models of decision making.
AB  - The authors develop and test generalized versions of take-the-best (TTB) and
      rational (RAT) models of multiattribute paired-comparison inference. The
      generalized models make allowances for subjective attribute weighting,
      probabilistic orders of attribute inspection, and noisy decision making. A key
      new test involves a response-time (RT) approach. TTB predicts that RT is
      determined solely by the expected time required to locate the 1st discriminating
      attribute, whereas RAT predicts that RT is determined by the difference in summed
      evidence between the 2 alternatives. Critical test pairs are used that partially
      decouple these 2 factors. Under conditions in which ideal observer TTB and RAT
      strategies yield equivalent decisions, both the RT results and the estimated
      attribute weights suggest that the vast majority of subjects adopted the
      generalized TTB strategy. The RT approach is also validated in an experimental
      condition in which use of a RAT strategy is essentially forced upon subjects.

PMID- 17201557
TI  - Aware and (dis)liking: item-based analyses reveal that valence acquisition via
      evaluative conditioning emerges only when there is contingency awareness.
AB  - Evaluative conditioning (EC) refers to changes in the liking of an affectively
      neutral stimulus (the conditioned stimulus, or CS) following the pairing of that
      stimulus with another stimulus of affective value (the unconditioned stimulus, or
      US). In 3 experiments, the authors assessed contingency awareness, that is,
      awareness of the CS-US associations, by relying on participants' responses to
      individual items rather than using a global method of assessment. They found that
      EC emerged on contingency aware CSs only. Of note, whether the CSs were evaluated
      explicitly (Experiments 1 and 2) or implicitly (Experiment 3) did not make a
      difference. This pattern supports the idea that awareness of the CS-US
      associations may be required for valence acquisition via EC.

PMID- 17201558
TI  - Layout geometry in the selection of intrinsic frames of reference from multiple
      viewpoints.
AB  - Four experiments investigated the roles of layout geometry in the selection of
      intrinsic frames of reference in spatial memory. Participants learned the
      locations of objects in a room from 2 or 3 viewing perspectives. One view
      corresponded to the axis of bilateral symmetry of the layout, and the other
      view(s) was (were) nonorthogonal to the axis of bilateral symmetry. Judgments of
      relative direction using spatial memory were quicker for imagined headings
      parallel to the symmetric axis than for those parallel to the other viewing
      perspectives. This advantage disappeared when the symmetric axis was eliminated.
      Moreover, there was more consistency across participants in the selection of
      intrinsic axes when the layout contained an axis of bilateral symmetry than when
      it did not. These results indicate that the layout geometry affects the selection
      of intrinsic frames of reference supporting the intrinsic model of spatial memory
      proposed by W. Mou and T. P. McNamara (2002) and by A. L. Shelton and T. P.
      McNamara (2001).

PMID- 17201559
TI  - Available but unattended conceptual information in working memory: temporarily
      active semantic content or persistent memory for prior operations?
AB  - In 2 experiments, the authors investigated available but unattended information
      following working memory task demands. The experimental task presented a memory
      set containing exemplars from 2 conceptual categories. Following instructions to
      focus attention on only 1 category, priming of both categories was assessed with
      category comparisons of exemplar pairs. Priming was greatest for the focused
      category and for exemplars from the memory set (direct priming). Priming also
      extended to new exemplars of both categories (indirect priming) and showed little
      decline over more than 1 min of intervening processes. Finally, changing between
      category exemplars and features across memory set and comparison phases
      eliminated the indirect priming. These results support a persistent, operation
      specific, procedural account of available but unattended conceptual information
      in working memory.

PMID- 17201560
TI  - Aging, source memory, and misrecollections.
AB  - The authors propose an illusory recollection account of why cognitive aging is
      associated with episodic memory deficits. After listening to statements presented
      by either a female or a male speaker, older adults were prone to misrecollecting
      past events. The authors' illusory recollection account is instantiated in a new
      illusory recollection signal detection model that provides a better fit of older
      adults' data than does the standard signal detection model. They observed that
      age-related differences in source memory (as measured by source d' scores)
      virtually disappear after accounting for the occurrence of illusory
      recollections. These data suggest that age-related source memory impairments are
      not due to older adults' remembering less diagnostic source information and
      having to guess more. Instead, older adults appear to misremember past events
      more often than younger adults.

PMID- 17201561
TI  - Verb aspect and the activation of event knowledge.
AB  - The authors show that verb aspect influences the activation of event knowledge
      with 4 novel results. First, common locations of events (e.g., arena) are primed
      following verbs with imperfective aspect (e.g., was skating) but not verbs with
      perfect aspect (e.g., had skated). Second, people generate more locative
      prepositional phrases as completions to sentence fragments with imperfective than
      those with perfect aspect. Third, the amplitude of the N400 component to location
      nouns varies as a function of aspect and typicality, being smallest for
      imperfective sentences with highly expected locations and largest for
      imperfective sentences with less expected locations. Fourth, the amplitude of a
      sustained frontal negativity spanning prepositional phrases is larger following
      perfect than following imperfective aspect. Taken together, these findings
      suggest a dynamic interplay between event knowledge and the linguistic stream.

PMID- 17201562
TI  - Within-category discontinuity interacts with verbal rule complexity in perceptual
      category learning.
AB  - A test of the predicted interaction between within-category discontinuity and
      verbal rule complexity on information-integration and rule-based category
      learning was conducted. Within-category discontinuity adversely affected
      information-integration category learning but not rule-based category learning.
      Model-based analyses suggested that some information-integration participants
      improved performance by recruiting more "units" in the discontinuous condition.
      Verbal rule complexity adversely affected rule-based category learning but not
      information-integration category learning. Model-based analyses suggested that
      the rule based effect was on both decision criterion learning and variability in
      decision criterion placement. These results suggest that within-category
      discontinuity and decision rule complexity differentially impact information
      integration and rule-based category learning and provide information regarding
      the detailed processing characteristics of these two proposed category learning
      systems.

PMID- 17201563
TI  - Reversing the truth effect: learning the interpretation of processing fluency in
      judgments of truth.
AB  - Repeated statements receive higher truth ratings than new statements. Given that
      repetition leads to greater experienced processing fluency, the author proposes
      that fluency is used in truth judgments according to its ecological validity.
      Thus, the truth effect occurs because people learn that fluency and truth tend to
      be positively correlated. Three experiments tested this notion. Experiment 1
      replicated the truth effect by directly manipulating processing fluency;
      Experiment 2 reversed the effect by manipulating the correlation between fluency
      and truth in a learning phase. Experiment 3 generalized this reversal by showing
      a transfer of a negative correlation between perceptual fluency (due to color
      contrast) and truth to truth judgments when fluency is due to prior exposure
      (i.e., repetition).

PMID- 17201564
TI  - Separating bias and sensitivity in judgments of associative memory.
AB  - Ratings of the degree of association between words are linearly related to normed
      associative strengths, but the intercept is high, and the slope is shallow (the
      judgments of associative memory [JAM] function). Two experiments included
      manipulations intended to decrease the intercept and increase the slope.
      Discrimination training on many pairs of words and constraining ratings to sum to
      a constant both reduced the intercept but failed to change the slope. The
      intercept of the JAM function appears to contain a bias component that can be
      manipulated independently of the slope, which reflects sensitivity to associative
      strengths.

PMID- 17201565
TI  - The role of memory for past test in the underconfidence with practice effect.
AB  - According to the Memory for Past Test (MPT) heuristic, judgments of learning
      (JOLs) may be based, in part, on memory for the correctness of answers on a
      previous test. The authors explored MPT as the source of the underconfidence with
      practice effect (UWP; A. Koriat, L. Sheffer, & H. Ma'ayan, 2002), whereby Trial 1
      overconfidence switches to underconfidence by Trial 2. Immediate and delayed JOLs
      were contrasted because only immediate JOLs demonstrate UWP. Consistent with MPT
      for immediate JOLs, Trial 1 test performance better predicted Trial 2 JOLs than
      did Trial 2 test performance. Delayed JOLs showed the reverse. Furthermore, items
      forgotten on Trial 1 but remembered on Trial 2 contributed disproportionately to
      UWP, but only with immediate JOLs.

PMID- 17201566
TI  - Transfer of noncorresponding spatial associations to the auditory Simon task.
AB  - Four experiments examined transfer of noncorresponding spatial stimulus-response
      associations to an auditory Simon task for which stimulus location was
      irrelevant. Experiment 1 established that, for a horizontal auditory Simon task,
      transfer of spatial associations occurs after 300 trials of practice with an
      incompatible mapping of auditory stimuli to keypress responses. Experiments 2-4
      examined transfer effects within the auditory modality when the stimuli and
      responses were varied along vertical and horizontal dimensions. Transfer occurred
      when the stimuli and responses were arrayed along the same dimension in practice
      and transfer but not when they were arrayed along orthogonal dimensions. These
      findings indicate that prior task-defined associations have less influence on the
      auditory Simon effect than on the visual Simon effect, possibly because of the
      stronger tendency for an auditory stimulus to activate its corresponding
      response.

PMID- 17201567
TI  - Pushing the limits of imagination: mental practice for learning sequences.
AB  - In 2 experiments, the efficacy of motor imagery for learning to type number
      sequences was examined. Adults practiced typing 4-digit numbers. Then, during
      subsequent training, they either typed in the same or a different location,
      imagined typing, merely looked at each number, or performed an irrelevant task.
      Repetition priming (faster responses for old relative to new numbers) was
      observed on an immediate test and after a 3-month delay for participants who
      imagined typing. Improvement across the delay in typing old and new numbers was
      found for the imagined and actual typing conditions but not for the other
      conditions. The findings suggest that imagery can be used to acquire and retain
      representations of sequences and to improve general typing skill.

PMID- 17201568
TI  - Threat-related attentional bias in anxious and nonanxious individuals: a meta
      analytic study.
AB  - This meta-analysis of 172 studies (N = 2,263 anxious,N = 1,768 nonanxious)
      examined the boundary conditions of threat-related attentional biases in anxiety.
      Overall, the results show that the bias is reliably demonstrated with different
      experimental paradigms and under a variety of experimental conditions, but that
      it is only an effect size of d = 0.45. Although processes requiring conscious
      perception of threat contribute to the bias, a significant bias is also observed
      with stimuli outside awareness. The bias is of comparable magnitude across
      different types of anxious populations (individuals with different clinical
      disorders, high-anxious nonclinical individuals, anxious children and adults) and
      is not observed in nonanxious individuals. Empirical and clinical implications as
      well as future directions for research are discussed.

PMID- 17201569
TI  - If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary
      adrenocortical axis in humans.
AB  - The notion that chronic stress fosters disease by activating the hypothalamic
      pituitary-adrenocortical (HPA) axis is featured prominently in many theories. The
      research linking chronic stress and HPA function is contradictory, however, with
      some studies reporting increased activation, and others reporting the opposite.
      This meta-analysis showed that much of the variability is attributable to
      stressor and person features. Timing is an especially critical element, as
      hormonal activity is elevated at stressor onset but reduces as time passes.
      Stressors that threaten physical integrity, involve trauma, and are
      uncontrollable elicit a high, flat diurnal profile of cortisol secretion.
      Finally, HPA activity is shaped by a person's response to the situation; it
      increases with subjective distress but is lower in persons with posttraumatic
      stress disorder.

PMID- 17201570
TI  - Comprehending envy.
AB  - The authors reviewed the psychological research on envy. The authors examined
      definitional challenges associated with studying envy, such as the important
      distinction between envy proper (which contains hostile feelings) and benign envy
      (which is free of hostile feelings). The authors concluded that envy is
      reasonably defined as an unpleasant, often painful emotion characterized by
      feelings of inferiority, hostility, and resentment caused by an awareness of a
      desired attribute enjoyed by another person or group of persons. The authors
      examined questions such as why people envy, why envy contains hostile feelings,
      and why it has a tendency to transmute itself. Finally, the authors considered
      the role of envy in helping understand other research domains and discussed ways
      in which people cope with the emotion.

PMID- 17201571
TI  - The nature of procrastination: a meta-analytic and theoretical review of
      quintessential self-regulatory failure.
AB  - Procrastination is a prevalent and pernicious form of self-regulatory failure
      that is not entirely understood. Hence, the relevant conceptual, theoretical, and
      empirical work is reviewed, drawing upon correlational, experimental, and
      qualitative findings. A meta-analysis of procrastination's possible causes and
      effects, based on 691 correlations, reveals that neuroticism, rebelliousness, and
      sensation seeking show only a weak connection. Strong and consistent predictors
      of procrastination were task aversiveness, task delay, self-efficacy, and
      impulsiveness, as well as conscientiousness and its facets of self-control,
      distractibility, organization, and achievement motivation. These effects prove
      consistent with temporal motivation theory, an integrative hybrid of expectancy
      theory and hyperbolic discounting. Continued research into procrastination should
      not be delayed, especially because its prevalence appears to be growing.

PMID- 17201572
TI  - The influence of outcome desirability on optimism.
AB  - People are often presumed to be vulnerable to a desirability bias, namely, a
      tendency to be overoptimistic about a future outcome as a result of their
      preferences or desires for that outcome. In this article, this form of wishful
      thinking is distinguished from the more general concepts of motivated reasoning
      and overoptimism, and the evidence for this bias is reviewed. The authors argue
      that despite the prevalence of the idea that desires bias optimism, the empirical
      evidence regarding this possibility is limited. The potential for desires to
      depress rather than enhance optimism is discussed, and the authors advocate for
      greater research attention to mediators of both types of effects. Nine possible
      mediational accounts are described, and critical issues for future research on
      the desirability bias are discussed.

PMID- 17201574
TI  - The evidence for a neurobiological model of childhood antisocial behavior.
AB  - Children with persistent antisocial and aggressive behavior are diagnosed as
      having disruptive behavior disorder. The authors review evidence that antisocial
      children, and especially those who persist with this behavior as they grow older,
      have a range of neurobiological characteristics. It is argued that serotonergic
      functioning and stress-regulating mechanisms are important in explaining
      individual differences in antisocial behavior. Moreover, low fear of punishment
      and physiological underactivity may predispose antisocial individuals to seek out
      stimulation or take risks and may help to explain poor conditioning and
      socialization. The authors propose a theoretical model highlighting the interplay
      between neurobiological deficits and cognitive and emotional functioning as
      mediators of the link between early adversity and antisocial behavior problems in
      childhood. Implications for intervention programs are discussed.

PMID- 17201576
TI  - Integrating generational perspectives in nursing.
AB  - Although nurses from four different generations work closely together, tension
      may occur as the different generational perspectives result in misinterpretation
      and misunderstanding. Learning to create integrated and collegial relationships
      with people from different generations is a critical skill for nurses who work in
      multigenerational teams. This article will begin with a review of the historical
      perspective of the four generational cohorts currently in the workplace. This
      review will set a foundation for understanding each generation's unique set of
      work and personal values. Then the article will discuss various sources of
      multigenerational misunderstandings and conclude with a discussion of approaches
      to strengthen intergenerational work teams. The article will emphasize that
      learning to appreciate the diverse points of view, leverage the strengths, and
      value the differences in colleagues from various generations can enable
      individuals to form creative, adaptable, and cohesive work groups.

PMID- 17201573
TI  - Autobiographical memory specificity and emotional disorder.
AB  - The authors review research showing that when recalling autobiographical events,
      many emotionally disturbed patients summarize categories of events rather than
      retrieving a single episode. The mechanisms underlying such overgeneral memory
      are examined, with a focus on M. A. Conway and C. W. Pleydell-Pearce's (2000)
      hierarchical search model of personal event retrieval. An elaboration of this
      model is proposed to account for overgeneral memory, focusing on how memory
      search can be affected by (a) capture and rumination processes, when mnemonic
      information used in retrieval activates ruminative thinking; (b) functional
      avoidance, when episodic material threatens to cause affective disturbance; and
      (c) impairment in executive capacity and control that limits an individual's
      ability to remain focused on retrieval in the face of distraction.

PMID- 17201577
TI  - Leading a multigenerational nursing workforce: issues, challenges and strategies.
AB  - Today's nursing workforce is made up of staff and nursing leaders from four
      different generational cohorts. Generational diversity, including workforce
      differences in attitudes, beliefs, work habits, and expectations, has proven
      challenging for nursing leaders. The purpose of this article is to assist nursing
      leaders to reframe perceptions about generational differences and to view these
      differences in attitudes and behaviors as potential strengths. Developing the
      skill to view generational differences through a different lens will allow the
      leader to flex their leadership style, enhance quality and productivity, reduce
      conflict, and maximize the contributions of all staff. This article provides an
      overview of the generational cohorts and presents strategies which nursing
      leaders can use to coach and motivate, communication with, and reduce conflict
      for each generational cohort of nurses.

PMID- 17201578
TI  - Addressing multigenerational conflict: mutual respect and carefronting as
      strategy.
AB  - This article addresses the challenges faced by nurses as they work side-by-side
      with nurses from a variety of generational cohorts. First a brief overview of the
      generational characteristics of the four generational cohorts in today's
      workplace is presented. Next the importance of each nurse using respect and
      carefronting as antidotes to generational conflict is discussed. Finally the role
      of nursing leadership in facilitating respect and carefronting is noted.

PMID- 17201579
TI  - Adapting your teaching to accommodate the net generation of learners.
AB  - Educators are faced with the challenge of adapting their teaching styles to
      accommodate a new generation of learners. The Net Generation or Millennials, who
      are now entering colleges and universities, have learning expectations, styles,
      and needs different from past students. This article assists educators in
      teaching the Net Generation by highlighting the characteristics of the Net
      Generation and providing examples of how to adapt teaching strategies to
      accommodate the Net Generation, in light of their preferences for digital
      literacy, experiential learning, interactivity, and immediacy.

PMID- 17201580
TI  - Inter-group conflict in health care: UK students' experiences of bullying and the
      need for organisational solutions.
AB  - This paper addresses bullying of United Kingdom (UK) nursing students whilst on
      work placement as a specific issue of inter-group difficulty that currently
      affects nurses and students working in the UK National Health Service. The
      authors begin by discussing the concept of bullying and sharing the types of
      bullying reported in two recent studies involving UK nursing students. Both
      studies illustrate the effects that negative workplace experiences can have on
      new entrants to the profession. After reviewing various individual solutions
      which have been recommended for reducing bullying, they suggest that the most
      effective solution is for health care organisations offering placement training
      to become much more proactive in creating a culture that will not tolerate
      bullying behaviour by staff at any level. The literature suggests bullying is a
      phenomenon affecting workplaces in many countries. Thus the issues described in
      this article, and the solutions offered have relevance to a variety of health
      care settings.

PMID- 17201581
TI  - Safe staffing in Massachusetts: a year of legislative action.

PMID- 17201582
TI  - Is the Doctor of Nursing Practice ethical?

PMID- 17201583
TI  - MedlinePlus: key resource for both health consumers and health professionals.

PMID- 17201584
TI  - Differences in home cage behavior and endocrine parametres in rats of four
      strains.
AB  - OBJECTIVE: The majority of studies that involve behavioral testing in different
      rat strains is based on measuring behavioral responses to stressful situations in
      a novel environment. Very little is known on the spontaneous behavior in rat
      strains. The aim of the present study was to compare home cage behavior and basal
      hormone levels in two outbred rat strains, Sprague-Dawley (SD) and Wistar as well
      as two inbred strains, Lewis and Spontaneously Hypertensive Rats (SHR). METHODS:
      Twenty-eight male rats from four strains of rats (n=7/strain) were used in this
      study. Behavior of each rat in his home cage was recorded by a video camera for
      45 minutes during the dark phase of the day. The parameters considered included
      rearing, jumps, ambulation, grooming, feeding/drinking and no movements. Blood
      plasma was analyzed for aldosterone, plasma renin activity (PRA),
      adrenocorticotropin hormone (ACTH) and corticosterone by specific
      radioimmunoassays. RESULTS: One-way ANOVA revealed significant inter-strain
      differences in counts of jumps and rearing. In comparison with Sprague-Dawley and
      Wistar rats, Lewis rats displayed significantly more jumps and rearing.
      Statistical analysis showed significant inter-strain differences in the levels of
      aldosterone and of plasma renin activity. The highest levels of aldosterone were
      found in Lewis rats. Plasma renin activity was significantly lower in SHR than in
      Sprague-Dawley rats. Correlation analysis failed to reveal any relationships
      between behavioral and endocrine parameters. Significant strain differences were
      observed also in relative weights of the spleen, adrenals and thymus. CONCLUSION:
      Plasma renin activity and basal mineralocorticoid secretion did not show parallel
      pattern if compared among different rat strains. Locomotor activity in the home
      cage, which could represent general activity to be considered in evaluating
      emotional responses, was highest in the Lewis rats.

PMID- 17201585
TI  - Weight change and androgen levels during contraceptive treatment of women
      affected by polycystic ovary.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of oral
      contraceptive Diane 35 (ethinylestradiol + cyproteroneacetate EE/CPA) which is
      widely used in the treatment of PCOS in Europe, on body weight, lipid levels and
      endocrine parameters in non-obese women with PCOS. SUBJECTS AND METHODS: Nineteen
      PCOS women were examined in the early follicular phase of menstrual cycle, blood
      samples for the estimation of cholesterol (C), HDL cholesterol (HDL-C),
      triglycerides (TG), testosterone (T), androstenedione (A), dehydroepiandrosterone
      sulfate (DHEAS) and sex hormone binding globulin (SHBG) were taken before the
      start of treatment with Diane 35 and again after 7 +/- 3.8 months of treatment
      with Diane 35. Body weight (W) was recorded at the time of both examinations.
      RESULTS: After the treatment with Diane 35 the levels of W (p<0.05), total C
      (p<0.05), TG (p<0.004) and SHBG (p<0.0001) increased significantly. In addition,
      significant negative correlation between SHBG levels before treatment and
      increase of W after Diane 35 was found (r= -0.56; p<0.02). Increase of W
      correlated negatively with T before treatment (r= 0.58; p< .02) and positively
      with the change in T level after treatment (r=0.50; p<0.05). CONCLUSIONS:
      Increase of body weight in a significant number of PCOS-affected women was seen
      after treatment with Diane 35 and it is assumed to blunt ameliorating effects of
      this treatment on androgen levels. Considering our findings, we conclude that the
      treatment with CPA/EE can result in significant weight gain ameliorating positive
      effects of the treatment on androgen levels. These findings could underline the
      necessity of the finding new therapeutical options for PCOS, besides
      contraception. Studies concerning body composition during contraceptive treatment
      in PCOS would be also useful in the future.

PMID- 17201586
TI  - Exogenous IL-1beta induces its own expression, but not that of IL-6 in the
      hypothalamus and activates HPA axis and prolactin release.
AB  - OBJECTIVE: Proinflammatory cytokines IL-1beta, and IL-6 are synthesized in the
      brain, where they exert local regulatory functions. Our aim was to find out
      whether, along with the activation of hypothalamo-pituitary-adrenocortical (HPA)
      axis and prolactin (PRL), the acute systemic enhancement of IL-1beta affects its
      own production in the hypothalamus as well as that of IL-6. METHOD: Forty five
      minutes after a single i.p. administration of recombinant rat IL-1beta (5
      microg/kg) to male Long Evans rats we estimated the expression of IL-1beta and IL
      6 mRNA in the hypothalamus by real time PCR, ACTH, corticosterone (CORT), and PRL
      by RIA RESULTS: IL-1beta administration stimulated the expression of IL-1beta
      mRNA in the hypothalamus by 99 %, but not that of IL-6. It also significantly
      activated plasma levels of ACTH, PRL, CORT, and CORT production in adrenal gland.
      CONCLUSION: These results indicate that acute peripheral enhancement of IL-1beta
      may induce neuroendocrine changes also via the immediate activation of its own
      expression in the hypothalamus, but not that of IL-6 expression in the
      hypothalamus was found.

PMID- 17201587
TI  - BRAF mutations in papillary thyroid carcinoma.
AB  - Papillary thyroid carcinoma (PTC) is the most frequent malignant neoplasm of the
      thyroid originating from the thyroid follicular cell (TFC). Although the
      formation of PTC is believed to result from rearrangements of RET or TRK
      oncogenes or MET point mutations, these structural aberrations or point mutations
      do not correlate with the clinicopathological features of PTC and do not seem to
      be a useful prognostic marker of the disease. Therefore, further experiments
      should be carried out in order to find new practical clinical markers. Recently,
      oncogene BRAF has become a subject of great interest. The mutation of BRAF gene
      is characteristic for PTC and poorly differentiated and/or undifferentiated
      cancers derived from PTC. The occurrence of BRAF mutation has often been observed
      in various human tumours. The presence of mutation was confirmed in melanoma,
      colon cancer, gliomas and lung cancer. In the majority of cases, there is only
      one type of point mutation - V600E. The RAS/RAF/MEK/MAPK kinase pathway mediates
      the cellular response to mitogenic signals. BRAF gene mutation results in
      increased kinase activity, leading to excessive activation of the above mitogenic
      pathway and to uncontrolled proliferation of cancer cells. Some correlation was
      noticed between BRAF gene mutation and the clinical stage of the neoplastic
      disease in question. Preliminary investigations indicate that the presence of
      BRAF mutation might be a valuable diagnostic and prognostic marker of the
      disease. Further investigations could also bring further improvements into the
      therapeutic management of thyroid cancer. There are reports emphasizing the
      possibility of using the inhibitors of BRAF proteins in the treatment of PTC.
      Certainly, in order to confirm the diagnostic usefulness of this marker, further
      studies should be carried out.

PMID- 17201589
TI  - Componential analysis of interpersonal perception data.
AB  - We examine the advantages and disadvantages of 2 types of analyses used in
      interpersonal perception studies: componential and noncomponential. Componential
      analysis of interpersonal perception data (Kenny, 1994) partitions a judgment
      into components and then estimates the variances of and the correlations between
      these components. A noncomponential analysis uses raw scores to analyze
      interpersonal perception data. Three different research areas are investigated:
      consensus of perceptions across social contexts, reciprocity of attraction, and
      individual differences in self-enhancement. Finally, we consider criticisms of
      componential analysis. We conclude that interpersonal perception data necessarily
      have components (e.g., perceiver, target, measure, and their interactions), and
      that the researcher needs to develop a model that best captures the researcher's
      questions.

PMID- 17201588
TI  - No associations between genetic polymorphisms of TGF-beta, PAI-1, and COL1A1, and
      bone mineral density in Caucasian females.
AB  - OBJECTIVE: The aim of this study was to examine whether variants in genes for
      transforming growth factor beta1 (TGF-beta1; Leu10>Pro and Arg25>Pro),
      plasminogen activator inhibitor 1 (PAI-1; 4G>5G variant) and collagen 1 (COL1A1;
      Sp1 variant) may be useful in identifying individuals with increased
      susceptibility to early postmenopausal bone loss within the population of Czech
      women. METHODS: Polymorphisms were genotyped (by PCR and restriction analysis) in
      1400 females representatively selected from the Czech population as well as in
      218 postmenopausal osteoporotic women 40-70 years of age (mean age 58,7 years)
      and a 151 postmenopausal females within the same age range (mean age 59,1 years)
      with normal BMD. RESULTS: We have not found any statistically significant
      differences in the frequency of individual genotypes or alleles of analyzed
      variants between the groups of osteoporotic patients (OP), population group (PG)
      and control group (CG). The frequency of the individual genotypes in the analyzed
      groups was as follows 1) TGF-beta1 gene: Leu10Leu10 OP 30.2 %, PG 35.6 %, CG 35.1
      %; Leu10Pro10 OP 52.1 %, PG 47.1 %, CG 50.0 %; Pro10Pro10 OP 17.7 %, PG 17.3 %,
      CG 14.9 %; 2) TGF-beta1 gene Arg25 homozygotes OP 83.8 %, PG 86.1%, CG 89.3 %,
      Pro25 carriers OP 16.2 %, PG 13.9 %, CG 10.7 %, 3) PAI-1 gene: 4G4G OP 34.9 %, PG
      31.8, CG 28.5 %, 5G4G OP 43.6 %, PG 46.7 %, CG 50.3 %, 5G5G OP 21.5 %, PG 21.5%,
      CG 21.2%, and 4) COL1A-1 ("SS" homozygotes, OP 63.0%, PG 63.7%, CG 64.6 %, "s"
      carriers OP 37.0 %, PG 36.3 %, CG 35.1 %). CONCLUSIONS: Variants in genes for TGF
      beta1 (Leu10>Pro and Arg25>Pro), PAI-1 (4G>5G) and COL1A1 (Sp1 variant) are not
      associated with low BMD in postmenopausal Czech Caucasian females.

PMID- 17201590
TI  - Positive conceptions of perfectionism: approaches, evidence, challenges.
AB  - Almost 30 years ago, Hamachek (1978) suggested that 2 forms of perfectionism be
      distinguished, a positive form labeled "normal perfectionism" and a negative form
      labeled "neurotic perfectionism." Focusing on the positive, we present an
      overview of the different empirical conceptions of the 2 forms of perfectionism
      and a common framework for the 2 basic approaches: the dimensional approach
      differentiating 2 dimensions of perfectionism (perfectionistic strivings and
      perfectionistic concerns) and the group-based approach differentiating 2 groups
      of perfectionists (healthy perfectionists and unhealthy perfectionists).
      Moreover, we review the evidence demonstrating that (a) perfectionistic strivings
      are associated with positive characteristics and (b) healthy perfectionists show
      higher levels of positive characteristics compared to unhealthy perfectionists
      and nonperfectionists. Although questions on core facets, positive effects, and
      developmental antecedents of positive forms of perfectionism remain, our findings
      suggest that self-oriented perfectionistic strivings are positive, if
      perfectionists are not overly concerned about mistakes and negative evaluations
      by others.

PMID- 17201591
TI  - The new reinforcement sensitivity theory: implications for personality
      measurement.
AB  - In this article, we review recent modifications to Jeffrey Gray's (1973, 1991)
      reinforcement sensitivity theory (RST), and attempt to draw implications for
      psychometric measurement of personality traits. First, we consider Gray and
      McNaughton's (2000) functional revisions to the biobehavioral systems of RST.
      Second, we evaluate recent clarifications relating to interdependent effects that
      these systems may have on behavior, in addition to or in place of separable
      effects (e.g., Corr, 2001; Pickering, 1997). Finally, we consider ambiguities
      regarding the exact trait dimension to which Gray's "reward system" corresponds.
      From this review, we suggest that future work is needed to distinguish
      psychometric measures of (a) fear from anxiety and (b) reward-reactivity from
      trait impulsivity. We also suggest, on the basis of interdependent system views
      of RST and associated exploration using formal models, that traits that are based
      upon RST are likely to have substantial intercorrelations. Finally, we advise
      that more substantive work is required to define relevant constructs and
      behaviors in RST before we can be confident in our psychometric measures of them.

PMID- 17201592
TI  - Intergroup threat and outgroup attitudes: a meta-analytic review.
AB  - This article examines the relationship between intergroup threat and negative
      outgroup attitudes. We first qualitatively review the intergroup threat
      literature, describing the shift from competing theories toward more integrated
      approaches, such as the integrated threat theory (ITT; W. G. Stephan and Stephan,
      2000). The types of threats discussed include: realistic threat, symbolic threat,
      intergroup anxiety, negative stereotypes, group esteem threat, and
      distinctiveness threat. We then conducted a quantitative meta-analysis examining
      the relationships between various intergroup threats and outgroup attitudes. The
      meta-analysis, involving 95 samples, revealed that 5 different threat types had a
      positive relationship with negative outgroup attitudes. Additionally, outgroup
      status moderated some of these relationships. Implications and future directions
      are considered.

PMID- 17201593
TI  - Evolutionary origins of leadership and followership.
AB  - Drawing upon evolutionary logic, leadership is reconceptualized in terms of the
      outcome of strategic interactions among individuals who are following different,
      yet complementary, decision rules to solve recurrent coordination problems. This
      article uses the vast psychological literature on leadership as a database to
      test several evolutionary hypotheses about the origins of leadership and
      followership in humans. As expected, leadership correlates with initiative
      taking, trait measures of intelligence, specific task competencies, and several
      indicators of generosity. The review finds no link between leadership and
      dominance. The evolutionary analysis accounts for reliable age, health, and sex
      differences in leadership emergence. In general, evolutionary theory provides a
      useful, integrative framework for studying leader-follower relationships and
      generates various novel research hypotheses.

PMID- 17201594
TI  - Vicarious retribution: the role of collective blame in intergroup aggression.
AB  - We provide a new framework for understanding 1 aspect of aggressive conflict
      between groups, which we refer to as vicarious retribution. Vicarious retribution
      occurs when a member of a group commits an act of aggression toward the members
      of an outgroup for an assault or provocation that had no personal consequences
      for him or her but which did harm a fellow ingroup member. Furthermore,
      retribution is often directed at outgroup members who, themselves, were not the
      direct causal agents in the original attack against the person's ingroup. Thus,
      retribution is vicarious in that neither the agent of retaliation nor the target
      of retribution were directly involved in the original event that precipitated the
      intergroup conflict. We describe how ingroup identification, outgroup
      entitativity, and other variables, such as group power, influence vicarious
      retribution. We conclude by considering a variety of conflict reduction
      strategies in light of this new theoretical framework.

PMID- 17201599
TI  - Personal use of work computers: distraction versus destruction.
AB  - To explore definitions, frequencies, and motivation for personal use of work
      computers, we analyzed 329 employees' responses to an online survey, which asked
      participants to self-report frequencies for 41 computer behaviors at work. This
      sample (65% female, 74% European ethnicity, mean age of 36 years) was formed by
      soliciting participants through Internet Usenet groups, emails, and listservs.
      Results support a distinction between computer use that is counterproductive and
      that which is merely not productive. Nonproductive Computer Use occurred more
      when employees were younger (r = -0.31, p < 0.01), had Internet access at work
      longer (r = +0.16, p < 0.01), and had faster Internet connections at work than at
      home (r = +0.14, p < 0.01). Counterproductive Computer Use occurred more when
      Internet access was newer (r = -0.16, p < 0.01) and employees knew others who had
      been warned about misuse (r = +0.11, p < 0.05). While most employees who engaged
      in computer counterproductivity also engaged in computer nonproductivity, the
      inverse was uncommon, suggesting the need to distinguish between the two when
      establishing computer policies and Internet accessibility.

PMID- 17201600
TI  - Gender, Internet use, and sexual behavior orientation among young Nigerians.
AB  - This study examined the influence of gender and Internet use on the sexual
      behavior orientation of young adults in Nigeria. Using an ex-post-facto design,
      data were collected from a total of 231 participants. Results of the hierarchical
      regression model provided support for the influence of gender and Internet use on
      sexual behavior orientation among young Nigerians. Further, results also revealed
      an interaction effect; as the use of the Internet increased, male participants
      reported a greater extent of risky sexual behavior orientation than their female
      counterparts. The findings were explained in the context of the theoretical
      foundations of the study, while practical implications for combating youths'
      risky sexual behavior orientation were highlighted.

PMID- 17201601
TI  - Personality and self-reported use of mobile phones for games.
AB  - Mobile phones are popular devices that may generate problems for a section of the
      community. A previous study using the Eysenck Personality Questionnaire found
      that extraverts with low self-esteem reported more problems with their mobile
      phone use. The present study used the NEO FI and Coopersmith Self-Esteem
      Inventory to predict the self reported mobile phone use of 112 participants.
      Multiple regression found that people low on agreeableness were more likely to
      use their mobile phones to play games. The findings imply an interplay between
      personality traits and excessive or problematic use on mobile phones that is
      relevant to proposed innovations such as gambling on mobile phones.

PMID- 17201602
TI  - Does virtual intimacy exist? A brief exploration into reported levels of intimacy
      in online relationships.
AB  - This study examined the levels of intimacy reported by individuals in face-to
      face and computer-mediated (or "virtual") romantic relationships. As suggested by
      the media and promised by online dating services, some degree of intimacy was
      reported in computer-mediated relationships, but stronger intimacy was reported
      in all participants' face-to-face relationships. Results also indicated that
      individuals who had online, virtual relationships reported less intimacy in their
      own face-to-face relationships compared to individuals who had engaged
      exclusively in face-to-face relationships, suggesting that people may turn to
      virtual relating after challenges in their face-to-face experiences.

PMID- 17201603
TI  - Why are adolescents addicted to online gaming? An interview study in Taiwan.
AB  - The purpose of this study was twofold: to investigate the conscious and
      unconscious psychological motivations of online game addicts, and to further
      discuss the relationship between surface and source motivations. Ten Taiwanese
      adolescents with online game addiction were selected for in-depth interviews.
      Through sentence completion test and semi-structured interviews, data were
      collected and analyzed from the following four realms: (1) surface motivations,
      (2) source motivations, (3) self-conception, and (4) interpersonal relationships
      in real life. After content analysis, five categories with distinct themes were
      formed: (1) addicts' psychological needs and motivations; (2) online games as the
      everyday focus of the addicts; (3) the interplay of real self and virtual self;
      (4) online games as the compensatory or extensive satisfaction for addicts'
      needs; and (5) addicts' self-reflections. The implications of the present study
      are discussed.

PMID- 17201604
TI  - What is the internet? Taiwanese high school students' perceptions.
AB  - This study gathered 588 Taiwan high school students' responses about their
      perceptions of the Internet. The high school students highlighted the views that
      the Internet was a technology and a tool. Further analyses revealed that the
      students in lower grades and female students tended to conceptualize that the
      Internet was mainly a technology. On the other hand, the students in higher
      grades or male students emphasized other pragmatic aspects of the Internet, such
      as using it for functional or pleasure purposes, for instance, using the Internet
      as a tool, a toy, or a method of guiding a tour.

PMID- 17201605
TI  - Motivations for play in online games.
AB  - An empirical model of player motivations in online games provides the foundation
      to understand and assess how players differ from one another and how motivations
      of play relate to age, gender, usage patterns, and in-game behaviors. In the
      current study, a factor analytic approach was used to create an empirical model
      of player motivations. The analysis revealed 10 motivation subcomponents that
      grouped into three overarching components (achievement, social, and immersion).
      Relationships between motivations and demographic variables (age, gender, and
      usage patterns) are also presented.

PMID- 17201609
TI  - Posters Most Relevant to Child and Adolescent Psychopharmacology: The 46th Annual
      National Institute of Mental Health (NIMH) New Clinical Drug Evaluation Unit
      (NCDEU) Meeting, Boca Raton, Florida, USA, June 12-15, 2006.

PMID- 17201610
TI  - The efficacy and tolerability of quetiapine versus divalproex for the treatment
      of impulsivity and reactive aggression in adolescents with co-occurring bipolar
      disorder and disruptive behavior disorder(s).
AB  - OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of
      quetiapine and divalproex for the treatment of impulsivity and reactive
      aggression in adolescents with co-occurring bipolar disorder and disruptive
      behavior disorders. METHOD: Patients were included in this post hoc analysis if
      they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited
      Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current
      diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime
      and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct
      disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the
      36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria.
      These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or
      divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded
      study. The primary efficacy measure was change in PANSS Excited Component (EC)
      score over the study period and at each time point. RESULTS: Repeated measures
      analysis of variance (ANOVA) demonstrated statistically significant within
      treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p <
      0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the
      PANSS EC. There were no statistically significant treatment group differences in
      PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed
      regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was
      no significant difference in the rate of improvement in the PANSS EC scores
      between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28].
      CONCLUSIONS: Quetiapine and divalproex showed similar efficacy for the treatment
      of impulsivity and reactive aggression related to co-occurring bipolar and
      disruptive behavior disorders in adolescents. Quetiapine and divalproex are both
      useful as monotherapy for the treatment of impulsivity and reactive aggression in
      adolescents with bipolar and disruptive behavior disorders. Placebo-controlled
      studies are necessary.

PMID- 17201611
TI  - A naturalistic evaluation of intramuscular ziprasidone versus intramuscular
      olanzapine for the management of acute agitation and aggression in children and
      adolescents.
AB  - OBJECTIVE: The aim of this study was to compare the efficacy and safety of
      intramuscular ziprasidone versus intramuscular (i.m.) olanzapine in treating
      aggression in youth. METHODS: A retrospective chart review of 100 hospitalized
      patients less than 18 years of age treated with either i.m. ziprasidone or i.m.
      olanzapine for agitation or aggression was conducted. Comparisons were performed
      using statistical analysis of data collected from medical records. RESULTS:
      Baseline demographics were similar in the i.m. olanzapine and ziprasidone
      treatment groups regarding age and ethnicity; however, gender differences did
      reach statistical significance (p < 0.001). Dosing between children and
      adolescents significantly differed in the olanzapine group, whereas dosing was
      comparable in the ziprasidone group. No significant differences between the
      olanzapine and ziprasidone treatment groups were noted regarding length of stay,
      efficacy of the study medications, number of restraints, and duration of
      restraints. Ziprasidone subjects received significantly more doses of emergency
      medication during their hospital stay and significantly more doses of ziprasidone
      were administered with concomitant lorazepam or antihistamines. CONCLUSIONS: The
      results suggest i.m. ziprasidone and intramuscular olanzapine may be equally
      effective in treating aggression in youth. These agents may also be similar with
      regard to safety because no clinically significant adverse events were reported
      for either treatment group. The possibility of poor documentation of adverse
      events and side effects prevents formulating definitive conclusions regarding
      safety from this study.

PMID- 17201612
TI  - Developmental differences according to age at onset in juvenile bipolar disorder.
AB  - BACKGROUND: This study on a large sample of unselected, consecutive children and
      adolescents referred to a third-level hospital who received a diagnosis of
      bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as
      compared with adolescent-onset BD, presents specific clinical features in terms
      of severity, functional impairment, course, prevalent mood, pattern of co
      morbidity, and treatment outcome. METHODS: A total of 136 patients, 81 males
      (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
      diagnosis of BD according to a structured clinical interview Schedule for
      Affective Disorders and Schizophrenia for School-Age Children-Present and
      Lifetime Version (KSADS-PL), were included in the study. RESULTS: Eighty patients
      (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an
      adolescents-onset BD. Compared with the adolescent-onset BD, patients with
      childhood-onset were more frequently males and had a more frequent co-morbidity
      with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant
      disorder (ODD). An episodic course was found in only 42.5% of bipolar children,
      but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment
      outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not
      differentiate the two groups. CONCLUSIONS: Our findings suggest that a very early
      age at onset may identify a form of BD with a more frequent subcontinuous course
      and a heavy co-morbidity with ADHD.

PMID- 17201613
TI  - A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an
      exploratory study.
AB  - dl-Methylphenidate (MPH) has been widely used to treat attention
      deficit/hyperactivity disorder (ADHD) for the last half century. It had been
      exclusively available in the racemic form, i.e., a 50:50 mixture of d- and l
      isomers. However, a single enantiomer formulation, d-MPH (dexmethylphenidate),
      became available for general clinical use in 2002. For this reason, the intrinsic
      pharmacological differences in the effects of d- and l-MPH have recently come
      under intense investigation. The primary therapeutic effects of MPH are generally
      recognized to reside in the d-isomer. The present investigation provides
      quantitative values for a broad range of receptor-level interactions of the
      individual MPH isomers to better characterize the distinction between dl-MPH
      versus d-MPH versus l-MPH as it relates to binding affinity at sites associated
      with relevant central nervous system (CNS) pharmacology, as well as peripheral
      physiology. Overall, there were few differences in binding affinities between d
      MPH and the racemate whereas there were more apparent differences between d-MPH
      and l-MPH. d-MPH exhibited prominent affinity at the norepinephrine transporter
      (NET) site, even exceeding such affinity at the dopamine transporter (DAT). These
      results further demonstrate that affinity for catecholaminergic sites largely
      resides in the d-MPH isomer. Although binding affinity was not demonstrable at
      the serotonin (5-HT) transporter site (SERT), novel findings of the study
      included affinity for the 5-HT1A and 5-HT2B receptor sites for both d- and l-MPH,
      with d-MPH exerting by far the most predominant effects at these sites. Thus, the
      emerging data of favorable therapeutic effects of ADHD treatment with d-MPH (and
      dl-MPH) may be underpinned by affinity and potential pharmacologic effects at NET
      and DAT sites, as well as sites relevant to serotonergic neurotransmission that
      may modulate mood, cognition, and motor behavior. However, the present
      exploratory studies reflect receptor binding affinities only. The specific
      pharmacological activities (i.e., agonism vs. antagonism) of these compounds
      await further exploration.

PMID- 17201614
TI  - Placebo-controlled study of the effects of atomoxetine on bladder control in
      children with nocturnal enuresis.
AB  - INTRODUCTION: Nocturnal enuresis is a condition in which children at least 5
      years of age are incontinent of urine at night. Atomoxetine, a potent inhibitor
      of the presynaptic norepinephrine transporter, is used to treat attention
      deficit/hyperactivity disorder (ADHD). This study tested the hypothesis that
      atomoxetine will provide significant therapeutic benefit for nocturnal enuresis
      in patients with the diagnosis of nocturnal enuresis. METHODS: Atomoxetine's
      efficacy for improving nocturnal enuresis was studied in 87 pediatric subjects
      using an outpatient, multicenter, randomized, double-blind, parallel, placebo
      controlled study. Efficacy was determined by measuring the mean number of dry
      nights per week using an intent-to-treat analysis of the primary outcome measure,
      the Dry Night Log-Parent Report (DNL-PR), a daily parent diary. RESULTS: Baseline
      and end point DNL-PR data were available from 42 atomoxetine-treated and 41
      placebo-treated subjects. Atomoxetine increased the average number of dry nights
      per week by 1.47 compared with .60 for placebo (F = 7.06; df = (1, 75); p =
      0.01). Fifteen atomoxetine-treated subjects (35.7%) had an increase of at least 2
      dry nights per week compared with only 6 (14.6%) placebo-treated subjects
      (Fisher's exact test; p = 0.042). There were no significant differences in
      adverse events between the groups. CONCLUSIONS: Compared with placebo,
      atomoxetine treatment was associated with a significant increase in dry nights in
      children with nocturnal enuresis.

PMID- 17201615
TI  - Atomoxetine treatment in children and adolescents with attention-deficit
      hyperactivity disorder: what are the long-term health-related quality-of-life
      outcomes?
AB  - OBJECTIVE: Numerous investigations have examined the efficacy of pharmacological
      treatment for attention-deficit/hyperactivity disorder (ADHD) in children.
      However, relatively few studies have addressed the impact of treatment on long
      term subjective, psychosocial outcomes, such as health-related quality of life
      (HRQL). This study examines the long-term effects of pharmacological treatment
      with atomoxetine on HRQL in children and adolescents with ADHD. METHODS:
      Participants included 6- to 17-year-old children and adolescents (n = 912) with
      ADHD enrolled in a 24-month, multicenter, open-label trial of atomoxetine.
      Outcomes included clinician ratings of ADHD, parent ratings of ADHD, and a widely
      used measure of HRQL (The Child Health Questionnaire (CHQ)). Treatment response
      rates were calculated based on a CHQ improvement of at least 1 standard error of
      measurement. RESULTS: Significant improvements in HRQL were found following both
      acute and long-term treatment for psychosocial but not physical health. Of
      participants who completed treatment (n = 312 or 34.2% of those enrolled), 81%
      responded to acute treatment and 78% responded to long-term treatment.
      Improvements noted after acute treatment were maintained during long-term
      treatment with the majority of participants (86%) continuing to respond to
      treatment. CONCLUSIONS: Atomoxetine is associated with improvements in HRQL, and
      the improvements are generally stable over time.

PMID- 17201616
TI  - The influence of risperidone on attentional functions in children and adolescents
      with attention-deficit/hyperactivity disorder and co-morbid disruptive behavior
      disorder.
AB  - This study aims to examine the influence of risperidone on various attentional
      functions, including intensity and selectivity aspects of attention plus
      inhibitory control in children with attention deficit/hyperactivity disorder
      (ADHD) with co-morbid Disruptive Behavior Disorders (DBD) and normal IQ. Children
      with ADHD and DBD, aged 8-15 years, were treated with risperidone (mean daily
      dose: 1.5 mg; n = 23) and examined with three attentional paradigms before and
      after a 4-week treatment period. Age- and IQ-matched normal controls (n = 23)
      were also tested without medication on the same two occasions. No influence of
      the medication could be detected for any neuropsychological variable, neither as
      a positive enhancement nor as adverse side effects. However, clinical symptoms of
      ADHD and DBD assessed on the IOWA Conners Scale significantly improved after the
      4-week treatment period. Divergent behavioral and cognitive effects of
      risperidone on ADHD symptoms were observed, with a significant reduction in
      behavioral symptoms, whereas no positive treatment effects were found on
      laboratory tasks of impulsivity. Thus, the cognitive effects of risperidone seem
      to differ from the cognitive effects of stimulant treatments in children with
      ADHD + DBD. However, no negative impact of risperidone was observed on
      attentional functions either, i.e., there was no slowing of cognitive speed.

PMID- 17201617
TI  - Attention-deficit hyperactivity disorder symptoms in a clinic sample of children
      and adolescents with pervasive developmental disorders.
AB  - OBJECTIVES: The aims of this systematic chart review were to determine the
      frequency of attention-deficit/hyperactivity disorder (ADHD) in a clinic sample
      of children and adolescents with autism spectrum disorders (ASD), to compare ADHD
      symptoms in children with Autistic Disorder, Asperger's Disorder, and pervasive
      developmental disorders-not otherwise specified (PDD-NOS), to compare ADHD
      symptoms in individuals with and without ADHD-related chief complaints, and to
      determine the correlation between ADHD Rating Scale (ADHD RS) scores and age.
      METHOD: This systematic chart review examined data from children and adolescents
      who were consecutively referred to a university-based autism psychopharmacology
      program. All individuals were diagnosed by semistructured interview for ASD and
      ADHD, and ADHD symptoms were assessed using ADHD RS scores. RESULTS: Of 83
      children, 78% fulfilled Diagnostic and Statistical Manual of Mental Disorders,
      4th edition (DSM-IV) criteria for ADHD and exceeded the 93rd percentile norm for
      the ADHD RS. Hyperactivity-impulsivity scores were significantly greater in
      individuals with autism than those with other ASDs. DSM-IV ADHD diagnosis was
      represented equally in individuals with and without ADHD as their chief
      complaints. ADHD RS hyperactivity-impulsivity and total scores were negatively
      correlated with age. CONCLUSION: ADHD symptoms are pervasive in clinically
      referred children and adolescents with ASD.

PMID- 17201618
TI  - Psychotropic medication use in human immunodeficiency virus-infected youth
      receiving treatment at a single institution.
AB  - A cross-sectional study designed to document the use of psychotropic medication
      in a population of human immunodeficiency virus (HIV)-infected children and
      adolescents (n = 64) found 45% of the sample had been prescribed at least one
      psychotropic medication over a 4-year period. The most common medication category
      prescribed was antidepressants (30%), followed by stimulant-type medications
      (25%). This study suggests that psychotropic medications are commonly prescribed
      to HIV-infected children and adolescents. Close partnership with mental health
      professionals to develop treatment approaches for psychiatric disorders in youth
      living with HIV is recommended.

PMID- 17201620
TI  - Substance use, suicidality, and adolescent-onset schizophrenia: an Israeli 10
      year retrospective study.
AB  - OBJECTIVE: The aim of this study was to investigate the link between the use of
      specific types of substances and suicidality in adolescent inpatients with
      schizophrenia and schizoaffective disorder. METHODS: We performed a 10-year
      naturalistic retrospective study of 178 adolescent inpatients diagnosed as
      suffering from either schizophrenia or schizoaffective disorder. A comparison was
      made between the suicide-attempting adolescent inpatients and the non-attempting
      subjects, by the use of specific types of substances, measurements of psychotic,
      depressive, and aggressive symptoms, and clinical data reported during their
      hospitalization. RESULTS: The suicide attempters reported considerably greater
      usage of inhalants and lysergic acid diethylamide (LSD). Alcohol and methylene
      dioxy-methylamphetamine (MDMA) were also used significantly more by this group.
      However, no differences were found in the usage of cannabis, amphetamines,
      cocaine, and opiates. The suicide-attempting patients were found to have had more
      previous psychiatric admissions, a greater level of deliberate self-harm
      behavior, and a higher level of suicide ideation, but a decreased severity of
      psychotic symptoms. CONCLUSIONS: This study is the first report of the
      association between specific types of substances and suicidality in the high-risk
      population of adolescent psychotic inpatients. The strong association between
      inhalants, LSD, alcohol, and MDMA with suicidality is relevant to suicide
      prevention and intervention programs in adolescent-onset schizophrenia.

PMID- 17201619
TI  - Safety and efficacy of rivastigmine in adolescents with Down syndrome: a
      preliminary 20-week, open-label study.
AB  - Individuals with Down syndrome (DS) exhibit a cholinergic deficiency similar to
      that found in Alzheimer's disease. Cholinesterase inhibitors, used to treat
      Alzheimer's disease, may improve cognitive function in individuals with DS. This
      is the first investigation of the safety and efficacy of rivastigmine (an acetyl
      and butyryl cholinesterase inhibitor) on specific cognitive domains in pediatric
      DS. Eleven subjects with DS (ages 10-17 years) were treated with a liquid
      formulation of rivastigmine. Four subjects experienced no adverse events (AEs).
      Seven subjects reported AEs that were mild, transient and consistent with adverse
      events typically noted with cholinesterase inhibitors. Significant improvements
      were found in overall adaptive function (Vineland Adaptive Behavior Scales and
      Clinician's Interview-Based Impression of Change), attention (Leiter Attention
      Sustained tests A and B), memory (NEPSY: Narrative and Immediate Memory for Names
      subtests) and language (Test of Verbal Expression and Reasoning and Clinical
      Evaluation of Language Fundamentals-Preschool) domains. Improved language
      performance was found across all functional levels. These results underscore the
      need for larger, controlled studies employing a carefully constructed test
      battery capable of measuring the full scope of performance across multiple
      domains and a wide range of functional levels.

PMID- 17201621
TI  - Stimulants, neuroleptics, and children's friendship training for children with
      fetal alcohol spectrum disorders.
AB  - BACKGROUND: Peer relationship problems are a significant part of the clinical
      presentation of children with Fetal Alcohol Spectrum Disorders (FASD). Many of
      these children have been prescribed psychotropic medications by community
      practitioners. The present study reports on the interaction between medication
      status and parent and teacher-reported outcomes for parent-assisted Children's
      Friendship Training (CFT). METHODS: Seventy seven children (40 boys and 37 girls,
      age range was 71-139 months) diagnosed with FASD were given 12 sessions of CFT.
      Parent- and teacher-reported social outcomes were compared across four subgroups
      of children who were prescribed either stimulant or neuroleptic medication,
      neither or both types of medications. RESULTS: According to parent and teacher
      reports, children prescribed neuroleptic medication showed greater improvement on
      all outcome measures when compared to children not prescribed neuroleptics. In
      contrast, children prescribed stimulant medication either failed to show
      improvement or showed poorer outcomes when compared to children not prescribed
      stimulants. IMPLICATIONS: Children with FASD frequently present with symptoms of
      inattention and hyperactivity. The present results suggest physicians routinely
      ask about prenatal alcohol exposure as part of history taking to treat children
      more effectively who appear to be displaying attention-deficit/hyperactivity
      disorder symptomatology but who may have FASD.

PMID- 17201623
TI  - The challenges of psychopharmacological management of children with severe
      developmental disabilities.

PMID- 17201624
TI  - The cost of over-the-counter substance abuse.

PMID- 17201625
TI  - Reboxetine use in the treatment of attention-deficit/hyperactivity disorder.

PMID- 17201626
TI  - Methylphenidate and hypertension.

PMID- 17201628
TI  - Antioxidants in the prevention of renal disease.
AB  - Reactive oxygen species (ROS) play a key role in the pathophysiological processes
      of renal diseases. The cellular damage is mediated by an alteration in the
      antioxidant status, which increases the concentration of ROS in the stationary
      state (oxidative stress). Oxidative stress mediates a wide range of renal
      impairments, from acute renal failure, rhabdomyolysis, obstructive nephropathy,
      hyperlipidemia, and glomerular damage to chronic renal failure and hemodialysis.
      Therefore, interventions favoring the scavenging and/or depuration of ROS
      (dietary and pharmacological antioxidants) should attenuate or prevent the
      oxidative stress, thereby mitigating against the subsequent renal damage.

PMID- 17201629
TI  - Green tea extract thermogenesis-induced weight loss by epigallocatechin gallate
      inhibition of catechol-O-methyltransferase.
AB  - Epidemiological studies have shown that intake of tea catechins is associated
      with a lower risk of cardiovascular disease. The antioxidative activity of tea
      derived catechins has been extensively studied. Reports have shown that green tea
      extract intake is associated with increased weight loss due to diet-induced
      thermogenesis, which is generally attributed to the catechin epigallocatechin
      gallate. That catechin-polyphenols are known to be capable of inhibiting catechol
      O-methyltransferase (the enzyme that degrades norepinephrine) is a possible
      explanation for why the green tea extract is effective in stimulating
      thermogenesis by epigallocatechin gallate to augment and prolong sympathetic
      stimulation of thermogenesis. Knowledge about thermogenesis-induced weight loss
      produced by green tea's epigallocatechin gallate and its ability to inhibit
      catechol-O-methyltransferase is important for health benefits and for prolonging
      the action of norepinephrine in the synaptic cleft.

PMID- 17201630
TI  - Effect of genistein with carnitine administration on lipid parameters and obesity
      in C57Bl/6J mice fed a high-fat diet.
AB  - Soy products are mainly composed of proteins, phytochemicals such as isoflavones,
      soy lipids, and carbohydrates. It is unclear whether an individual component
      alone or a combined effect of multiple bioactive compounds contributes to the
      beneficial properties of soy. We investigated the effect of dietary genistein
      (the principal soy isoflavone) alone and combined with L-carnitine to evaluate
      possible synergistic effects on the intentionally induced prediabetic state
      characterized by insulin resistance and obesity in C57Bl/6J mice fed a high-fat
      diet (HD). In the HD-alone group, abdominal and back fat relative to total body
      weight were significantly higher compared with other groups including those fed
      normal diet (ND). Among the HD groups, final weight gains of the HD plus
      genistein (HD+G) and HD plus genistein plus L-carnitine (HD+G+C) groups were
      lower compared with that of the control (HD-alone). Especially in liver, the
      results showed that genistein with carnitine transcriptionally up-regulated
      expressions of acyl-coenzyme A synthetase (ACS) and carnitine
      palmitoyltransferase-I (CPT-I) by approximately 50% and 40%, respectively,
      compared with genistein alone. However, the up-regulation of CPT-I did not
      directly reflect the enzyme activity of CPT-I. On the other hand, the effects of
      genistein and genistein with carnitine on the expressions of ACS and CPT-I in
      muscle were not significant. Our study suggests that genistein with carnitine
      exerts anti-obesity effects, probably by modulating peroxisome proliferator
      activated receptor-associated genes. However, further work is needed to elucidate
      the possible mechanisms by which genistein and carnitine intervene.

PMID- 17201631
TI  - L-carnitine stimulates lipolysis via induction of the lipolytic gene expression
      and suppression of the adipogenic gene expression in 3T3-L1 adipocytes.
AB  - We investigated the lipolytic effects of L-carnitine in 3T3-L1 adipocytes. L
      carnitine at 10-S100 nM suppressed lipid accumulation. The release of glycerol
      and free fatty acid into the medium was significantly increased by 1.5- and 1.7-
      fold, respectively, by the addition of 100 nM L-carnitine compared with the
      control (P < .05). The mRNA levels of hormone-sensitive lipase, carnitine
      palmitoyltransferase I-a, and acyl-coenzyme A oxidase, all of which participate
      in lipid catabolism, were increased in the presence of 100 nM L-carnitine by 2.8
      , 2.2-, and 1.6-fold, respectively (P < .05). However, the expression of
      peroxisome proliferator-activated receptor-gamma and adipose-specific fatty acid
      binding protein, which are involved in adipogenesis, were down-regulated by L
      carnitine in 3T3-L1 adipocytes (P < .05). These results suggest an anti-obesity
      action of L-carnitine. L-carnitine may modulate lipid metabolism by stimulation
      of lipolysis and beta-oxidation accompanied by corresponding changes in gene
      expression and suppression of adipogenic gene expression.

PMID- 17201632
TI  - Eucommia ulmoides Oliver leaf extract increases endogenous antioxidant activity
      in type 2 diabetic mice.
AB  - Eucommia ulmoides Oliver (Du-zhong) leaf extract was investigated for its
      antioxidant effects in type 2 diabetic animals, C57BL/KsJ-db/db mice. Du-zhong
      extract equivalent to 1% dried whole Du-zhong leaf (0.187 g of extract/100 g of
      diet) was added to the experimental diets for 6 weeks. The Du-zhong extract
      supplement significantly lowered blood glucose concentrations and elevated plasma
      paraoxonase activity compared with the control group. The activities of
      erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GSH-Px) were significantly higher in the Du-zhong group compared with
      the control group, while glutathione reductase (GR) activity was not different
      between groups. The activities of SOD, GSH-Px, and GR in liver and kidney were
      not affected by Du-zhong extract supplementation, whereas the CAT activity was
      significantly higher in the Du-zhong group than in the control group. Du-zhong
      extract supplementation resulted in lower levels of hydrogen peroxide and lipid
      peroxide in erythrocytes, liver, and kidney. These results suggest that the
      antioxidant activity of Du-zhong extract is potentially beneficial for the
      prevention and management of complications of type 2 diabetes.

PMID- 17201634
TI  - Inhibition of atherosclerosis in low-density lipoprotein receptor-negative mice
      by sesame oil.
AB  - Diet has profound effects on the development of atherosclerosis. Fatty acid
      composition, antioxidants, and other components such as lignans have major
      effects on the atherosclerotic process. Sesame oil has both mono- and
      polyunsaturated fatty acid constituents in equal proportions. In addition, it
      also has high levels of numerous antioxidants and inducers of peroxisome
      proliferator-activated receptor. The objective of this study was to determine the
      anti-atherosclerotic effects of sesame oil. In this study, male low-density
      lipoprotein (LDL) receptor (LDLR) -/- mice were fed atherogenic diet or
      atherogenic diet reformulated with the same level of sesame oil (sesame oil
      diet). Plasma lipids and atherosclerotic lesions were quantified after 3 months
      of feeding. Sesame oil-containing diet significantly reduced the atherosclerotic
      lesion formation and plasma cholesterol, triglyceride, and LDL cholesterol levels
      in LDLR -/- mice. These findings suggest that sesame oil could inhibit
      atherosclerosis lesion formation effectively, perhaps because of the synergistic
      actions of fatty acid and nonsaponifiable components.

PMID- 17201633
TI  - Effects of the Schisandra fructus water extract on cytokine release from a human
      mast cell line.
AB  - Schisandra fructus has been used for treatment of cough and thirst in Korea.
      However, its therapeutic mechanisms remain largely unclear. To investigate the
      biological effect of Schisandra fructus water extract (SFWE), we examined the
      effect of SFWE on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore
      A23187-induced pro-inflammatory cytokine secretion in the human mast cell line
      HMC-1. HMC-1 cells were stimulated with PMA plus A23187 in the presence or
      absence of SFWE. Tumor necrosis factor (TNF)-alpha, interleukin 6 (IL-6), and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) productions were
      measured by enzyme-linked immunosorbent assay and reverse transcription
      polymerase chain reaction. Inhibitory IkappaB/nuclear factor-kappaB (NF-kappaB)
      expression was assessed by western blot. SFWE suppressed PMA plus A23187-induced
      TNF-alpha, IL-6, and GM-CSF production in dose-dependent manners. Furthermore,
      SFWE inhibited IkappaB degradation and NF-kappaB nuclear translocation. These
      results suggest that SFWE inhibits the secretion of pro-inflammatory cytokines in
      HMC-1 cells through blockade of IkappaB degradation and NF-kappaB activation.
      Taken together, these findings may help elucidate the mechanism of action of this
      medicine in the modulation of mast cell activation in inflammatory conditions.

PMID- 17201635
TI  - Influence of genistein isoflavone on matrix metalloproteinase-2 expression in
      prostate cancer cells.
AB  - We investigated the expression of matrix metalloproteinase (MMP)-2 in human LNCaP
      and PC3 prostate cancer cell lines in response to genistein exposure. Initially
      we studied the phytosensitivity of the cells to genistein using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to determine
      percentage cell viability/inhibition and the terminal deoxynucleotidyl
      transferase-mediated fluorescein-dUTP nick end-labeling apoptosis assay to assess
      the type of cell death. The results revealed that genistein inhibited growth and
      proliferation in both PC3 (hormone-dependent) and LNCaP (hormone-independent)
      prostate cancer cell lines, that there was no significant difference in
      sensitivity to genistein between PC3 and LNCaP cells, and that the effect of
      genistein on the cells was dose- and time-dependent. The results also revealed
      that inhibition of cell growth in both PC3 and LNCaP cells was predominantly due
      to apoptotic cell death. These results were consistent with data in previous
      studies. This was followed by determination of the MMP-2 profile in response to
      genistein treatment. The results indicated a significant dose- and time-dependent
      inhibition of MMP-2 expression levels in both cells, with a highly significant
      negative correlation between MMP-2 levels and concentration of genistein. This is
      of phytotherapeutic significance in view of the pivotal role of MMP-2 expression
      in the pathogenesis of prostate cancer. Increasing expression of MMPs has been
      identified in many human cancers, including prostate cancer. Our findings
      indicate that genistein could be a potent therapeutic inhibitor of MMP-2 in line
      with current concepts of targeted treatment.

PMID- 17201636
TI  - A comparative evaluation of the anticancer properties of European and American
      elderberry fruits.
AB  - European elderberry (Sambucus nigra), recognized in Europe for its health
      promoting properties for many generations, is known to contain a range of
      anthocyanins, flavonoids, and other polyphenolics that contribute to the high
      antioxidant capacity of its berries. American elderberry (Sambucus canadensis),
      on the other hand, has not been cultivated, bred, and promoted as a medicinal
      plant like its better-characterized European counterpart. In this study, aqueous
      acetone extracts of the berries from these two species were fractionated and
      tested in a range of assays that gauge anticarcinogenic potential. Both
      cultivated S. nigra and wild S. canadensis fruits demonstrated significant
      chemopreventive potential through strong induction of quinone reductase and
      inhibition of cyclooxygenase-2, which is indicative of anti-initiation and
      antipromotion properties, respectively. In addition, fractions of S. canadensis
      extract showed inhibition of ornithine decarboxylase, an enzyme marker related to
      the promotion stage of carcinogenesis. Analysis of active fractions using mass
      spectrometry and liquid chromatography-mass spectrometry revealed, in addition to
      flavonoids, the presence of more lipophilic compounds such as sesquiterpenes,
      iridoid monoterpene glycosides, and phytosterols.

PMID- 17201638
TI  - Antioxidant capacity of Venezuelan honey in wistar rat homogenates.
AB  - The antioxidant effect of several polyphenolic compounds is well known. However,
      little is known about the antioxidant capacity of Venezuelan honey, which has a
      high content of polyphenolic compounds. In this work, the antioxidant capacity of
      a genuine honey produced in Merida, Venezuela was studied using the ferrous iron
      oxidation with xylenol orange method, the thiobarbituric acid method, and the
      determination of antioxidant activity. We found that this honey has the capacity
      to decrease significantly the concentration of lipid hydroperoxides and
      malondialdehyde, produced during the lipid peroxidation process, in a comparable
      way with other widely studied antioxidants such as melatonin and vitamin E. It
      was found that the antioxidant activity in the 50% honey dilution, the highest
      concentration we tested, was equivalent to a concentration of uric acid of 0.62
      mM.

PMID- 17201637
TI  - Asarum sieboldii extracts attenuate growth, acid production, adhesion, and water
      insoluble glucan synthesis of Streptococcus mutans.
AB  - Asarum sieboldii has been used in traditional folk medicine to treat dental
      caries and periodontal disease. In the present study, we investigated the
      inhibitory effect of the ethanol and aqueous extracts of A. sieboldii on the
      growth, acid production, adhesion, and water-insoluble glucan synthesis of
      Streptococcus mutans. The ethanol and aqueous extracts of A. sieboldii inhibited
      the growth and acid production of S. mutans. In the bacterial adherence assay,
      the ethanol and aqueous extracts of A. sieboldii significantly lowered the
      adherence of S. mutans. We also found that the ethanol and aqueous extracts of A.
      sieboldii significantly inhibited the synthesis of water-insoluble glucan by
      crude glucosyltransferase. These results suggest that A. sieboldii extracts may
      inhibit the caries-inducing properties of S. mutans. Further studies are
      necessary to clarify the active constituents of A. sieboldii extracts responsible
      for such biomolecular activities.

PMID- 17201639
TI  - Antioxidant capacity of crude extracts from clones of banana and plane species.
AB  - Banana and plane are the most important fruits in world trade, behind citric
      plants. In this work we studied the antioxidant capacity of banana and plane
      varieties of fruits obtained from interspecies crossed varieties of Musa
      acuminata and Musa balbisiana, named Harton plane, Cavendish banana, and Manzano
      banana. With this purpose we evaluated banana and plane crude extracts using the
      ferrous ion oxidation with xylenol orange method, the thiobarbituric acid method,
      determination of antioxidant activity, and effect on superoxide anion and
      hydroxyl radical and the radicals generated by ultraviolet light. The experiments
      showed that all extracts have the capacity to decrease the concentrations of
      lipid hydroperoxides and malondialdehyde, produced in the lipid peroxidation
      process, in a manner comparable to that of other widely studied antioxidants like
      melatonin and vitamin E. Moreover, all extracts had the capacity to inhibit the
      generation of superoxide anion, hydroxyl radical, and the radicals generated by
      ultraviolet light. When antioxidant activity was calculated, a value was found
      that was equivalent to a concentration of uric acid between 0.20 and 0.30 mM at
      the highest concentration of extract used, with uric acid being a potent
      antioxidant at 1 mM.

PMID- 17201640
TI  - Hepatoprotective and antioxidant activities of Vernonia amygdalina on
      acetaminophen-induced hepatic damage in mice.
AB  - Vernonia amygdalina Del. (Family Compositae) is used in Nigerian folk medicine as
      a tonic and remedy against constipation, fever, high blood pressure, and many
      infectious diseases. We have evaluated the hepatoprotective and antioxidant
      effects of an aqueous extract of V. amygdalina leaves against acetaminophen
      induced hepatotoxicity and oxidative stress in mice in vivo. Activities of liver
      marker enzymes in serum (glutamate-oxaloacetate transaminase, glutamate-pyruvate
      transaminase, lactate dehydrogenase, and alkaline phosphatase) and bilirubin
      levels were determined colorimetrically, while catalase activity, lipid
      peroxidation products, thiobarbituric acid-reactive substances (TBARS), iron, and
      total protein concentrations were measured in liver homogenate. Acetaminophen
      challenge (300 mg/kg, i.p) for 7 days caused significant (P < .01) increases in
      the levels of bilirubin, liver enzymes, TBARS, and iron, while catalase activity
      and total protein level were reduced significantly (P < .01). Preadministration
      of V. amygdalina resulted in a dose-dependent (50-100 mg/kg) reversal of
      acetaminophen-induced alterations of all the liver function parameters by 51.9
      84.9%. Suppression of acetaminophen-induced lipid peroxidation and oxidative
      stress by the extract was also dose-dependent (50-100 mg/kg). The results of this
      study suggest that V. amygdalina elicits hepatoprotectivity through antioxidant
      activity on acetaminophen-induced hepatic damage in mice.

PMID- 17201641
TI  - Cardioprotective effect of squalene on lipid profile in isoprenaline-induced
      myocardial infarction in rats.
AB  - We studied the cardioprotective effect of squalene on isoprenaline-induced
      myocardial infarction in male albino rats with respect to changes in the levels
      of lipid components in plasma and heart tissue. Prior administration of 2%
      squalene in feed for 45 days significantly reduced the isoprenaline-induced
      elevation in the levels of cholesterol, triglycerides, and free fatty acids in
      plasma and heart tissue of rats following myocardial infarction. It exerted an
      antilipidemic effect by reducing the level of low-density lipoprotein cholesterol
      with a parallel rise in the level of high-density lipoprotein cholesterol in
      plasma of experimental rats. A tendency to prevent the isoprenaline-induced
      depletion of phospholipids in the myocardium of experimental rats was also
      observed. In the present study, the pretreatment with squalene significantly
      counteracted the isoprenaline-induced lipid peroxidation and maintained the rats
      at near normal status. The results of the present study indicate that the overall
      cardioprotective effect of squalene is probably related to an inhibition of lipid
      accumulation by its hypolipidemic properties and/or its antioxidant properties.

PMID- 17201642
TI  - Behavioral and histologic neuroprotection of aqueous garlic extract after
      reversible focal cerebral ischemia.
AB  - The objective of the present study was to investigate the effects of aqueous
      garlic extract (AGE) on neurobehavioral activities, malondialdehyde (MDA) and
      reduced glutathione (GSH) levels, glutathione peroxidase (GPx), glutathione
      reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD),
      catalase (CAT), and sodium-potassium ATPase (Na(+),K(+)-ATPase) activities, and
      glutamate and aspartate content in a middle cerebral artery (MCA) occlusion
      (MCAO) model of acute cerebral ischemia in rats. The right MCA of male Wistar
      rats was occluded for 2 hours using intraluminal 4-0 monofilament, and
      reperfusion was allowed for 22 hours. MCAO caused significant depletion in GSH
      and its dependent enzymes (GPx, GR, and GST) and significant elevation of MDA,
      glutamate, and aspartate. The activities of Na(+),K(+)- ATPase, SOD, and CAT were
      decreased significantly by MCAO. The neurobehavioral activities (grip strength,
      spontaneous motor activity, and motor coordination) were also decreased
      significantly in the MCAO group. All of the alterations induced by ischemia were
      significantly attenuated by pretreatment with AGE (500 mg/mL/kg of body weight,
      i.p.) 30 minutes before the induction of MCAO and correlated well with
      histopathology by decreasing the neuronal cell death following MCAO and
      reperfusion. These findings suggest that AGE effectively modulates
      neurobehavioral and neurochemical changes in focal ischemia, most probably by
      virtue of its antioxidant properties.

PMID- 17201643
TI  - Tropical green leafy vegetables prevent garlic-induced hepatotoxicity in the rat.
AB  - Garlic (Allium sativum) is popularly consumed because of its role in the
      treatment and management of several diseases. However, unregulated and chronic
      intake of garlic can cause damage to cells through the production of free
      radicals. This study was carried out in order to assess the ability of some
      tropical green leafy vegetables (Telfairia occidentalis, Solanum macrocapon,
      Corchorus olitorius, Baselia alba, Cnidoscolus acontifolus, Amarantus cruentus,
      and Ocimum gratissimum) to prevent garlic-induced hepatotoxicity in rats. Wistar
      strain albino rats were fed diet containing 4% garlic along with or without 40%
      green leafy vegetable supplement for 14 days. Thereafter, the feeding trial was
      terminated, the serum of the blood was prepared, and the liver, spleen,
      intestine, and organ were isolated for gross pathological investigation. The
      results of the study revealed that there was a significant increase (P < .05) in
      serum glutamate-oxaloacetate transaminase (SGOT) and glutamate-pyruvate
      transaminase (SGPT) of the albino rats fed diet containing 4% garlic supplement
      when compared with the rats fed the basal diet without garlic and vegetable (40%)
      supplement. However, there was a significant decrease (P < .05) in the serum
      total protein and albumin levels in those rats. Conversely, there was a
      consistent significant decrease (P < .05) in the SGOT and SGPT of the rats fed
      diet containing garlic (4%) and T. occidentalis (40%) and C. acontifolus (40%)
      supplement compared with those rats fed diet containing garlic (4%) supplement,
      while there were no consistent significant decrease in those rats fed diet with
      garlic (4%) alongside with 40% of other leafy vegetables (S. macrocanum, C.
      olitorius, B. alba, A. cruentus, and O. gratissimum). An increase in serum level
      of total protein and albumin was also observed in the rats fed T. occidentalis
      and C. acontifolus. Thus, T. occidentalis and C. acontifolus proved to be better
      vegetables in preventing garlic-induced hepatotoxicity compared with the other
      vegetables used in this study.

PMID- 17201644
TI  - Comparative essential oil composition and antifungal effect of bitter fennel
      (Foeniculum vulgare ssp. piperitum) fruit oils obtained during different
      vegetation.
AB  - The chemical composition of the flower and unripe and ripe fruits from fennel
      (bitter) (Foeniculum vulgare ssp. piperitum) has been examined by gas
      chromatography and gas chromatography-mass spectrometry. The main identified
      components of the flower and unripe and ripe fruit oils were estragole (53.08%,
      56.11%, and 61.08%), fenchone (13.53%, 19.18%, and 23.46%), and alpha
      phellandrene (5.77%, 3.30%, and 0.72%), respectively. Minor qualitative and major
      quantitative variations for some compounds of essential oils were determined with
      respect to the different parts of F. vulgare. The oils exerted varying levels of
      antifungal effects on the experimental mycelial growth of Alternaria alternata,
      Fusarium oxysporum, and Rhizoctonia solani. The 40 ppm concentrations of fennel
      oils showed inhibitory effect against mycelial growth of A. alternaria, whereas
      10 ppm levels were ineffective. The analyses show that fennel oils exhibited
      different degrees of fungistatic activity depending on the doses.

PMID- 17201645
TI  - Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats.
AB  - The present study was designed to investigate the antihyperglycemic effect of
      Umbelliferone (UMB) in normal and streptozotocin (STZ)-diabetic rats. Diabetes
      was induced in adult male albino rats of the Wistar strain, weighing 180-200 g,
      by administration of STZ (40 mg/kg of body weight) intraperitoneally. Diabetic
      rats showed an increase in levels of blood glucose and glycosylated hemoglobin
      (HbA(1c)) and activities of gluconeogenic enzymes such as glucose-6-phosphatase
      and fructose-1,6-bisphosphatase, and a decrease in levels of plasma insulin,
      hemoglobin (Hb), and liver glycogen and activities of glucokinase and glucose-6
      phosphate dehydrogenase. Intraperitoneal administration of UMB (10, 20, and 30
      mg/kg of body weight) and glibenclamide (600 micro g/kg of body weight) in 10%
      dimethyl sulfoxide dissolved in water, for 45 days, produced significantly
      decreased levels of blood glucose and HbA(1c) and activities of glucose-6
      phosphatase and fructose-1,6-bisphosphatase, while elevating levels of plasma
      insulin, Hb, and liver glycogen and activities of glucokinase and glucose-6
      phosphate dehydrogenase to near normal levels in STZ-diabetic rats when compared
      with normal control rats. Normal rats treated with UMB (30 mg/kg of body weight)
      also showed a significant effect on glycemic control. Thus, our results show that
      UMB at 30 mg/kg of body weight possesses a promising antihyperglycemic effect
      that is comparable with glibenclamide.

PMID- 17201646
TI  - Regulatory behavior and skin temperature in mid-aged male rats on three different
      isoflavone-containing diets.
AB  - Soy isoflavones, the most abundant phytoestrogens, are known as endocrine
      modulators and appear to be an effective treatment in some women during
      perimenopause when symptoms such as hot flashes may be reduced. This study
      examined the effects of dietary soy isoflavones on regulatory behaviors such as
      body weight, food and water intake, and skin tail temperature by feeding male
      Long-Evans rats one of the three standard chows (Phyto-free, Phyto-200, and Phyto
      600) containing approximately 10-15 ppm, 200 ppm, and 600 ppm of isoflavones,
      respectively. In an apparent dose-dependent manner, body weight was decreased as
      a function of increasing isoflavone levels in the diets. The average skin tail
      temperature of Phyto-600-fed rats (25.5 degrees C) was significantly lower than
      Phyto-free (27.5 degrees C) values by approximately 2 degrees C. The rats on the
      Phyto-200 diet (26.6 degrees C) displayed a temperature in between the Phyto-free
      and Phyto-600 values. Similar to the body weight results, skin tail temperature
      was decreased in an apparent dose-dependent manner as a function of increasing
      isoflavone concentrations in the diets. These results suggest that consumption of
      soy isoflavones alters regulatory behaviors (such as body weight and food and
      water intake) and skin temperature regulation that may help explain, in part, the
      beneficial effects of soy isoflavones on obesity and hot flashes in humans.

PMID- 17201647
TI  - Dietary herbal supplements with phenylephrine for weight loss.
AB  - This study was designed to evaluate the efficacy and safety of a dietary herbal
      supplement containing citrus aurantium and phenylephrine in the treatment of
      obesity. Two pilot studies enrolled healthy subjects with body mass indexes 25-40
      kg/m(2) to similar 8-week weight loss programs. Safety was assessed by physical
      examination and laboratory tests at screening and 8 weeks. The first pilot study
      randomized eight subjects to citrus aurantium (herbal phenylephrine) or placebo.
      Body composition by DEXA scan, waist circumference, and resting metabolic rate
      (RMR) were measured at baseline and 8 weeks. Food intake and appetite ratings
      were measured at baseline and week 2. The second pilot study randomized 20
      subjects to two 2-hour RMR tests a week apart after phenylephrine (20 mg) or
      placebo followed by phenylephrine (20 mg) three times a day for 8 weeks. In the
      first pilot study, the citrus aurantium group gained 1.13 +/- 0.27 (mean +/- SEM)
      kg compared with 0.09 +/- 0.28 kg in the placebo group (P < .04). RMR at baseline
      rose more in the citrus aurantium group, 144.5 +/- 15.7 kcal/24 hours, than the
      placebo group, 23.8 +/- 28.3 kcal/24 hours (P < .002), but not at 8 weeks. DEXA,
      waist circumference, food intake, and hunger ratings were not different. In the
      second pilot study, the phenylephrine group lost 0.8 +/- 3.4 kg in 8 weeks (not
      significant), and RMR increased more in the phenylephrine group (111.5 +/- 32.6
      vs. 37.4 +/- 22.7 kcal/24 hours, P = .02). There were no significant safety
      issues in either study. Although no toxicity was seen, these pilot studies
      suggest phenylephrine is not efficacious for weight loss.

PMID- 17201648
TI  - Globin digest: no evidence for a weight loss mechanism.
AB  - This study was designed to document the mechanism through which globin digest, a
      dietary herbal supplement, might cause weight loss by exploring possible fat
      malabsorption, calorie malabsorption, energy expenditure, and fat oxidation. Six
      healthy subjects were placed on an outpatient diet for 14 days and given a meal
      containing 40.9 g of fat on days 5 and 11, and stools were collected for 72 hours
      after each meal for analysis of fecal fat content. Four grams of globin digest
      was given with one meal and placebo with the other. In another separate study,
      six subjects were placed on a 100-g fat, weight-maintaining diet for 14 days. All
      food was prepared by the Pennington Center (Baton Rouge, LA) metabolic kitchen.
      Globin digest (2 g) or placebo was given with each of three meals per day, and
      stool was collected for calorie determinations during the last 72 hours of each
      week. Subjects received globin digest during one of the 2 weeks and placebo
      during the other. Resting metabolic rate and respiratory quotient were measured
      on the last day of each 1-week period. There was no increase in 72-hour fecal fat
      or fecal calories by bomb calorimetry during either of the studies. There was no
      difference in the respiratory quotient. Globin digest did result in an increase
      in resting metabolic rate. However, this increase was not statistically
      significant. Globin digest, if effective, does not cause weight loss or fat loss
      through fat malabsorption or a relative increase in fat oxidation. Future studies
      are needed to document the efficacy of globin digest for weight loss in humans
      before further mechanistic investigation is attempted.

PMID- 17201649
TI  - Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma
      cholesterol in rats fed high-fat and high-cholesterol diet.
AB  - The flavonoid naringin was investigated for its differential effects on hepatic
      cholesterol regulation when supplemented for 3 weeks and 6 weeks. Sprague-Dawley
      rats were fed a high-fat and high-cholesterol diet with or without 0.02% naringin
      supplement for 3 or 6 weeks. Supplementation with naringin resulted in a
      significant decrease in the plasma cholesterol and triglyceride concentrations in
      the 6-week trial. Although high-density lipoprotein (HDL)-cholesterol was not
      altered in either trial, the HDL-cholesterol/total cholesterol ratio (in percent)
      was significantly higher, and the atherogenic index was significantly lower in
      the naringin-supplemented groups in the 6-week trial. The hepatic cholesterol
      content was also lowered by naringin supplementation only in the 6-week trial.
      The hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was lower in
      the rats supplemented with naringin for 6 weeks, while the hepatic acyl-coenzyme
      A:cholesterol acyltransferase activity was lower in both the 3-week and 6-week
      trials. Results indicate that supplementation with naringin for 3 weeks did not
      exhibit a hypolipidemic effect when given with a HFHC diet. Naringin can,
      however, be beneficial for lowering hepatic cholesterol biosynthesis and levels
      of plasma lipids when supplemented for 6 weeks in this animal model.

PMID- 17201650
TI  - Antihypertensive effects of Gynura procumbens extract in spontaneously
      hypertensive rats.
AB  - Aqueous extracts of Gynura procumbens (Lour.) Merr. were orally administered to
      spontaneously hypertensive (SHR) rats for 4 weeks, and antihypertensive effects
      were determined. Oral administration of 500 mg/kg of G. procumbens (Lour.) Merr.
      extract (GPE) resulted in significantly lower blood pressure in SHR rats compared
      with SHR rats not given GPE (P < .05). Furthermore, GPE-administered rats had
      significantly lower serum lactate dehydrogenase, creatine phosphate kinase, and
      increased nitric oxide (NO), a known vasodilator, compared with the non-GPE
      administered SHR group (P < .05). These results suggest that oral administration
      of aqueous GPE may be useful for prevention and treatment of hypertension through
      increasing NO production in blood vessels.

PMID- 17201651
TI  - Morinda pubescens JE Smith (Morinda tinctoria Roxb) fruit extract accelerates
      wound healing in rats.
AB  - This study investigated the wound healing properties of the chloroform extract of
      Morinda pubescens fruit in rats. Topical application of M. pubescens fruit
      extract at 20 mg/mL and 10 mg/mL concentrations appreciably accelerated wound
      healing in rats compared with controls. Complete wound contraction was achieved,
      and fresh hair began to grow in the entire wounded area within 15 days in animals
      treated with the 20 mg/mL chloroform fruit extract of M. pubescens compared with
      only 60% contraction without hair growth in control rats.

PMID- 17201652
TI  - Corni fructus scavenges hydroxy radicals and decreases oxidative stress in
      endothelial cells.
AB  - Corni fructus has been used as a tonic, analgesic, and diuretic in Korean herbal
      medicine. The present investigation was undertaken to evaluate the antioxidative
      effect of corni fructus and its capacity to protect cells against oxidative
      damage. The radical scavenging activity of corni fructus extracts was measured
      using 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the antioxidant activity was
      determined by measuring the peroxide value in a linoleic acid emulsion system. In
      addition, human umbilical vein endothelial cells (HUVECs) were treated with corni
      fructus extracts and incubated with H(2)O(2) to investigate protection against
      apoptosis induction. Both ethanol and water extracts of corni fructus produced
      higher DPPH radical scavenging activity than hexane, chloroform, and ethyl
      acetate extracts. Strong antioxidative activities of both water and ethanol
      extracts were observed in an emulsion system containing linoleic acid and
      phosphate buffer. The incubation of HUVECs with the addition of ethanol extract
      significantly decreased H(2)O(2)-initiated damage of endothelial cells, but the
      water extract did not. The pretreatment with ethanol extract, but not with water
      extract, significantly decreased apoptotic damage of the H(2)O(2)-treated HUVECs
      and kept the morphological normality. This study demonstrates that corni fructus
      is a potent antioxidant substance, and suggests that further investigation is
      needed to characterize the difference between extract types and to identify its
      antioxidant compounds.

PMID- 17201654
TI  - Exploiting 4-1BB costimulation for enhancing antiviral vaccination.
AB  - 4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is
      emerging as an important costimulatory molecule, particularly in the regulation
      of CD8(+) T cell responses. Costimulation through 4-1BB, such as by utilizing
      agonistic anti-4-1BB monoclonal antibodies, has been well studied in various
      tumor models. However, 4-1BB is also an important regulator of antiviral CD8(+) T
      cell responses. This review summarizes these findings and describes how 4-1BB is
      beginning to be exploited in terms of boosting antiviral vaccine responses.

PMID- 17201655
TI  - Filoviruses and the balance of innate, adaptive, and inflammatory responses.
AB  - The Filoviruses Marburg virus and Ebola virus are among the deadliest of human
      pathogens, causing fulminant hemorrhagic fevers typified by overmatched specific
      immune responses and profuse inflammatory responses. Keys to both vaccination and
      treatment may reside, first, in the understanding of immune dysfunctions that
      parallel Filoviral disease and, second, in devising ways to redirect and restore
      normal immune function as well as to mitigate inflammation. Here, we describe how
      Filoviral infections may subvert innate immune responses through perturbances of
      dendritic cells and neutrophils, with particular emphasis on the downstream
      effects on adaptive immunity and inflammation. We suggest that pivotal events may
      be subject to therapeutic intervention as Filoviruses encounter immune processes.

PMID- 17201656
TI  - Influenza virus infection of the murine uterus: a new model for antiviral
      immunity in the female reproductive tract.
AB  - Secretory IgA (S-IgA) mediates local immunity to influenza virus in the murine
      upper respiratory tract and may play an important role in local immunity to
      various microorganisms in the female reproductive tract as well. Although the
      presence of IgA in cervicovaginal or uterine secretions has been correlated with
      immunity to a number of pathogens, there has been no direct demonstration of the
      mediation of uterine antiviral immunity by S-IgA. Influenza virus, although not a
      normal pathogen of the reproductive tract, was used to develop a model for the
      investigation of mucosal immunity in the uterus. PR8 (H1N1) influenza virus
      injected into the ovarian bursa of BALB/c mice grew well, with peak titers
      between days 3 and 5. Intravenous injection of polymeric IgA anti-influenza virus
      monoclonal antibody before or 30 min after viral challenge protected mice against
      viral infection. We believe this work to be the first direct demonstration of S
      IgA-mediated antiviral uterine immunity. It provides a model for further
      investigation of immunity in the female reproductive tract.

PMID- 17201657
TI  - Hepatitis B virus DNA in unusual serological profiles of hepatitis B surface
      antigen-positive sera.
AB  - On the basis of a seroepidemiological survey of hepatitis B virus (HBV) infection
      conducted on 6208 random serum samples from four provinces of Thailand, we found
      19 of 246 (7.7%) hepatitis B surface antigen (HBsAg)-positive samples with
      unusual serological constellations of HBV infection. Ten samples tested positive
      for HBsAg, anti-HBc (anti-hepatitis B core antibody), and anti-HBs (anti
      hepatitis B surface antibody) markers (group I), 3 specimens were HBsAg and anti
      HBs positive without detectable anti-HBc (group II), and the remaining 6
      specimens showed only HBsAg (group III). In group I, 7 of 10 HBsAg-positive sera
      could be confirmed by HBsAg neutralization, yielding positive results for all
      samples. None of the group II sera were available in sufficient amounts for
      confirmation. In group III, five of six sera were confirmed by HBsAg
      neutralization, with four showing a positive reaction. HBV DNA was detected in 7
      of 10 (70%) specimens in group I, in 1 of 3 (33.3%) specimens in group II, and in
      3 of 6 (50%) specimens in group III. On the basis of HBsAg neutralization, HBV
      DNA was found in five of seven (71.4%) HBsAg-positive samples in group I and in
      three of four (75%) HBsAg-positive samples in group III, whereas the one
      confirmed HBsAg-negative sample in group III also remained negative for HBV DNA.
      Amino acid sequences were compared with those specifying the "a" determinant of
      the wild-type virus, particularly focusing on HBV-S protein variations between
      positions 110 and 160. Among 11 HBV DNA-positive sera, G145A was detected in 2
      samples in group I, with the remaining samples identical to the wild-type virus.
      These unusual serological profiles may be due to the altered immune response of
      the host or to HBV variants.

PMID- 17201658
TI  - Comparison of a dipstick dot-ELISA with commercial assays for anti-dengue virus
      IgM antibodies.
AB  - Dengue virus infections have undergone dramatic expansion in range, affecting
      several tropical and subtropical regions of the world. Dengue virus causes life
      threatening complications characterized by dengue hemorrhagic fever and dengue
      shock syndrome. No standard validated test systems are available for serological
      diagnosis of dengue virus infection. This creates problems in the diagnosis and
      proper management of patients. Evaluation of a Defense Research and Development
      Establishment (DRDE) dengue virus dipstick dot-ELISA test, developed in house,
      vis-a-vis commercially available immunodiagnostic kits was carried out for
      detection of IgM antibodies. The DRDE dengue dipstick dot-ELISA was performed on
      the basis of the dot-ELISA principle. Commercial tests, namely, the Panbio Dengue
      IgM Capture ELISA system (Panbio, Sinnamon Park, Australia) and Pathozyme Dengue
      M (Omega Diagnostics, Alva, UK), were performed according to the manufacturers'
      protocols. Ninety-one serum samples collected from the states of Kerala and
      Delhi, India during August and November of 2004 were used in the present study.
      The overall agreement among all three tests was found to be only 72.16% for IgM
      antibodies. Correlations between the DRDE dipstick dot-ELISA and the Panbio kit,
      between the DRDE dipstick dot-ELISA and the Pathozyme Dengue M kit, and between
      the Panbio kit and the Pathozyme Dengue M kit were found to be 96, 93, and 94%,
      respectively. Although the Panbio kit is widely used in various laboratories in
      India, the DRDE dipstick dot-ELISA promises to be a useful kit because of its
      field applicability and comparable sensitivity.

PMID- 17201659
TI  - Characterization and application of monoclonal antibodies against turbot
      (Scophthalmus maximus) Rhabdovirus.
AB  - Five monoclonal antibodies (mAbs), 1G8, 1H9, 2D2, 2D3, and 2F5, against
      Scophthalmus maximus rhabdovirus (SMRV) were prepared. Characterization of the
      mAbs included indirect enzyme-linked immunosorbent assay, isotyping, viral
      inhibition assay, immunofluorescence staining of virus-infected cell cultures,
      and Western blot analysis. Isotyping revealed that 1G8 and 1H9 were of the IgG2b
      subclass and that the other three were IgM. 2D2, 2D3, and 2F5 partially inhibited
      SMRV infection in epithelioma papulosum cyprinid (EPC) cell culture. Western
      blotting showed that all five mAbs could react with two SMRV proteins with
      molecular masses of approximately 30 kDa (P) and 26 kDa (M). These two proteins
      were localized within the cytoplasm of SMRV-infected EPC cells by
      immunofluorescence assay. Also, progressive foci of viral replication in cell
      cultures were monitored from 6 to 24 h, using mAb 2D3 as the primary antibody. A
      flow cytometry procedure was used to detect and quantify SMRV-infected (0.01
      PFU/cell) EPC cells with mAb 2D3, and 10.8% of cells could be distinguished as
      infected 36 h postinfection. Moreover, mAb 2D3 was successfully applied for the
      detection of viral antigen in cryosections from flounder tissues by
      immunohistochemistry tests.

PMID- 17201660
TI  - Effects of porcine reproductive and respiratory syndrome virus-infected antigen
      presenting cells on T cell activation and antiviral cytokine production.
AB  - The ability of porcine reproductive and respiratory syndrome virus (PRRSV) to
      suppress T cell expression of CD25 (alpha chain of interleukin [IL]-2 receptor),
      interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) was
      determined by flow cytometry in naive porcine T cells in response to mitogen
      (concanavalin A) and cytokine inducers (phorbol 12-myristate 13-acetate plus
      ionomycin [PMA/I]). Four PRRSV isolates of varying clinical virulence and three
      different types of porcine myeloid antigen-presenting cells (APCs) were used. T
      cells cultured with monocytes infected with virulent PRRSV (VR-2385, SDSU-73, and
      VR-2332), but not with a vaccine strain (Ingelvac PRRS MLV; Boehringer Ingelheim
      Vetmedica, St. Joseph, MO), demonstrated significantly reduced CD25 expression
      (%CD25(+)) and IFN-gamma expression (%IFN-gamma (+)) compared with T cells
      incubated with uninoculated monocyte cultures. T cells cultured with monocytes
      infected with all four PRRSV isolates demonstrated significantly reduced %TNF
      alpha (+). The significant reduction of %CD25(+), %IFN-gamma (+), and %TNF-alpha
      (+) was not detected in T cells cultured with monocyte-derived macrophages (MDMs)
      and immature monocyte-derived dendritic cells (MDCs) infected with any PRRSV
      isolates. Heat-inactivated PRRSV did not induce significantly reduced T cell
      responses in any APC cultures. The reduction of T cell response in monocyte
      cultures was not due to PRRSV-induced T cell death. Gene expression of IL-10
      detected by semiquantitative reverse transcriptase-polymerase chain reaction was
      significantly increased in virulent PRRSV-infected monocyte cultures after PMA/I,
      but not concanavalin A, stimulation compared with IL-10 gene expression from
      uninoculated monocyte cultures. Increased IL-10 gene expression contributed to
      significantly reduced %IFN-gamma (+) and %TNF-alpha (+), but not %CD25(+), as
      determined by IL-10 neutralization assay. This study reports that PRRSV has the
      ability to suppress T cell responses. The suppressive ability of PRRSV is
      associated with viral virulence and is mediated by virus-infected monocytes, but
      not by virus-infected MDMs and immature MDCs.

PMID- 17201661
TI  - Ethnicity and difference in dengue virus-specific memory T cell responses in
      Cuban individuals.
AB  - The different risk factors associated with dengue hemorrhagic fever pathogenesis
      needs yet additional clarification. The exceptional epidemiological circumstances
      in Cuba allow their evaluation in a well-defined situation. In the present study
      the memory T cell response of 80 Cuban donors previously infected with dengue-1
      and dengue-2 during the 1977 and 1981 epidemics, and belonging to different
      ethnic groups, was examined. White people showed, in contrast to black people,
      stronger and remarkably cross-reactive dengue virus-specific memory CD4(+) T
      lymphocyte proliferation and interferon-gamma release. The observed variation in
      T cell response according to ethnicity could be related to the immunopathogenesis
      of dengue hemorrhagic fever, and may partially explain the epidemiological
      evidence that black individuals are at lower risk for the most severe dengue
      clinical course compared with white individuals.

PMID- 17201662
TI  - T cell responses to respiratory syncytial virus fusion and attachment proteins in
      human peripheral blood mononuclear cells.
AB  - The cellular immune response to respiratory syncytial virus (RSV) is considered
      important in both protection and immunopathogenesis. We have studied the HLA
      class I- and class II-restricted T cell responses to RSV fusion (F) and
      attachment (G) proteins in peripheral blood mononuclear cells (PBMCs) obtained
      from healthy young adults. PBMCs were stimulated with autologous cells infected
      with recombinant modified vaccinia virus Ankara (rMVA) expressing RSV F (rMVA-F)
      or G (rMVA-G). In rMVA-F-stimulated bulk cultures F-specific CD4(+) and CD8(+) T
      cell responses were demonstrated, whereas in rMVA-G-stimulated cultures only G
      specific CD4(+) T cell responses were detected. Using a set of overlapping
      peptides spanning the F protein, a number of the F-specific T cell responses
      could be mapped to different antigenic regions, whereas for the G protein only
      CD4(+) T cell responses recognizing the central conserved domain could be
      detected. These results suggest that the RSV glycoprotein-specific T cell
      response is directed to a number of different epitopes. Further studies must be
      performed to confirm the apparent inability of the RSV G protein to induce CD8(+)
      T cell responses. The rMVA-based in vitro stimulation protocol will be useful to
      define protein-specific T cell responses in different viral systems.

PMID- 17201663
TI  - Simian immunodeficiency virus-induced CD4+ T cell deficits in cytokine secretion
      profile are dependent on monkey origin.
AB  - Facets of the immune response early after human immunodeficiency virus (HIV)
      infection influence the course of disease. In the simian immunodeficiency virus
      (SIV)-rhesus monkey system, a global dysfunction of CD4(+) T cell cytokine
      secretion was reported to develop early after infection [McKay PF, Barouch DH,
      Schmitz JE, Veazey RS, Gorgone DA, Lifton MA, Williams KC, and Letvin NL: J Virol
      2003;77:4695-4702]. Because differences have been found in SIV pathogenesis
      depending on the origin of the monkeys, we investigated the correlation between
      animal background, defined by country of origin (India or China), and circulating
      T cell cytokine secretion as well as cycling ability within the first 3 mo of SIV
      infection. An early loss of CD4(+) T cells that produce interferon (IFN)-gamma
      and interleukin (IL)-2, those that produce IFN-gamma but not tumor necrosis
      factor (TNF)-alpha, as well as those that do not express IFN-gamma but can
      express IL-2 or TNF-alpha, was observed in animals of Indian, but not of Chinese,
      origin after SIV infection. After infection CD4(+) T cells in Chinese macaques
      developed an increased proliferating pool of T cells compared with Indian
      animals. These data reveal host diversity in the global effects of SIV infection
      on functional subsets of immune cells, which can add to a better understanding of
      differences observed in populations from diverse ethnic origins.

PMID- 17201664
TI  - Evaluation of a self-inactivating lentiviral vector expressing simian
      immunodeficiency virus gag for induction of specific immune responses in vitro
      and in vivo.
AB  - Humoral and cellular immune responses have been shown to play a fundamental role
      in controlling simian and/or simian-human immunodeficiency virus (SIV-SHIV)
      replication in infected macaques. Therefore, the appropriate induction of both
      compartments of the immune system should be elicited after immunization. In this
      context, viral vectors have been proven effective in inducing both humoral and
      cellular immune responses during immunization protocols after direct injection in
      vivo. Among them, recombinant self-inactivating lentiviral vectors represent a
      useful strategy for vaccine development because they efficiently transduce and
      express foreign genes into a wide variety of mammalian cells. Here we report on
      the development and evaluation of a self-inactivating HIV-based lentiviral vector
      expressing a codon-optimized SIV Gag sequence (TY2-SIVGagDX), which when used to
      transduce dendritic cells mediated in vitro expansion of Gag-specific T cells
      derived from an SHIV-infected cynomolgus monkey, as measured by interferon (IFN)
      gamma enzyme-linked immunospot (ELISPOT) and (51)Cr release standard assays. To
      evaluate the ability to elicit specific immune responses in vivo, TY2-SIVGagDX
      was also employed in a vaccination protocol after a single intramuscular
      injection in BALB/c mice. Results indicated that the vector was able to
      efficiently induce both cellular and humoral responses, as measured by IFN-gamma
      ELISPOT assay and antibody production. These data further confirm that lentiviral
      vectors encoding viral genes represent an advantageous delivery system for
      vaccine development.

PMID- 17201665
TI  - Effective induction of type 1 cytotoxic T cell responses in mice with DNA vaccine
      encoding two hepatitis C virus cytotoxic T lymphocyte epitopes.
AB  - The aims of this study were to explain whether a multiple cytotoxic T lymphocyte
      (CTL) epitope-based anti-hepatitis C virus (HCV) DNA vaccine can induce specific
      CTL responses to each HCV CTL epitope independently and long-term CD8(+) T cell
      memory responses, and to determine the cytokine secretion pattern and subtype of
      epitope-specific cytotoxic T cells. A multi-CTL epitope gene, which consists of
      two epitopes of HCV (H-2(d)-restricted HCV core(133142) and E1(315322)), was
      cloned into the eukaryotic expression vector pcDNA3.1. BALB/c mice (H-2(d)
      restricted) were vaccinated intramuscularly with this multi-CTL epitope-based DNA
      vaccine. The epitope-specific CTLs against target cells (P815,H-2(d) restricted)
      pulsed with various CTL epitope peptides were detected by lactate dehydrogenase
      release assay, and the precursor frequency of epitope-specific CTLs was
      determined by limiting dilution analysis. Cytokines (interleukin [IL]-2, IL-4,
      and interferon-) in culture supernatants were determined by enzyme-linked
      immunosorbent assay. The multi-CTL epitope-based DNA vaccine directed against two
      HCV CTL epitopes could induce specific CTL responses to each of the two CTL
      epitopes independently and long-term CD8(+) T cell memory responses. The epitope
      specific cytotoxic T cells produced helper T cell type 1 cytokines. This work
      demonstrated that multiepitope DNA vaccination is a potential strategy to control
      HCV infection.

PMID- 17201666
TI  - Influence of aluminum-based adjuvant on the immune response to multiantigenic
      formulation.
AB  - Several adjuvants have been described and tested in humans. However, the aluminum
      based adjuvants remain the most widely used component in vaccines today. Emerging
      data suggest that aluminum phosphate and aluminum hydroxide adjuvants do not
      promote a strong commitment to the helper T cell type 2 (Th2) pathway when they
      are coadministered with some Th1 adjuvants. In this regard, subtle differences
      between both aluminum-based adjuvants have been demonstrated. We have previously
      shown that subcutaneous immunization, in aluminum phosphate, of a mixture
      comprising the surface and core antigens of hepatitis B virus (HBV) and the
      multiepitopic protein CR3 of human immunodeficiency virus type 1 elicits a CR3
      specific Th1 immune response. In these experiments, the antigens were adjuvated
      at the same time. As the final selection of the best adjuvant should be based on
      experimental evidence, we asked whether aluminum hydroxide allows a better Th1
      immune deviation than aluminum phosphate. We also studied several ways to mix the
      antigens and the impact on CR3-specific interferon (IFN)-gamma secretion. Our
      findings indicate that aluminum hydroxide allows better Th1 immunodeviation than
      aluminum phosphate adjuvant for the mixture of HBV antigens and CR3. In addition,
      CR3-specific IFN-gamma secretion of the various formulations tested was the same
      irrespective of the order in which the antigens were combined.

PMID- 17201667
TI  - Transforming growth factor-beta inhibits coxsackievirus-mediated autoimmune
      myocarditis.
AB  - Clinical myocarditis is a precursor to dilated cardiomyopathy and a principal
      cause of heart failure. Nearly 30% of all recently diagnosed cases of myocarditis
      are attributable to infection with coxsackie B virus (CBV), the most frequently
      associated pathogen. CBV initially replicates in the pancreas and quickly spreads
      to the heart, inducing chronic autoimmunity. To determine whether
      immunosuppressive cytokines could act to limit the extent of autoimmunity to the
      heart, we infected transgenic mice that express immunosuppressive cytokines in
      the pancreas. Herein, we demonstrate that transgenic expression of transforming
      growth factor-beta (1) (TGF-beta) within the pancreatic beta cells prevented mice
      from developing autoimmune myocarditis after CBV infection. In contrast,
      transgenic expression of interleukin-4 did not inhibit virus-mediated heart
      disease. Furthermore, we show that TGF-beta expression reduced viral replication
      while promoting the recruitment of macrophages into the pancreas. These results
      illustrate the benefit of TGF-beta in controlling not only viral replication, but
      also CBV-mediated autoimmunity.

PMID- 17201668
TI  - CXCR4 or CCR5 tropism of human immunodeficiency virus type 1 isolates does not
      determine the immunological milieu in patients responding to antiretroviral
      therapy.
AB  - Here we address whether CCR5 or CXCR4 tropism of the predominant viral strain
      detected before or on combination antiretroviral therapy (ART) explains why some
      human immunodeficiency virus (HIV)-infected patients who begin ART with advanced
      HIV disease retain low interferon (IFN)-gamma responses, despite recovery of
      CD4(+) T cell counts. Tropism was determined by culture and confirmed by gp120 V3
      loop sequence of multiple plasma samples in eight adult male patients who began
      treatment with <50 CD4(+) T cells/microL. Four patients had mixed infections, one
      had only R5 HIV, and three had only X4 HIV. Of these, two carried CCR5Delta32.
      Viral tropism was not related to CD4(+) T cell counts or HIV RNA levels. When
      immunological responses were monitored over several years, IFN-gamma responses to
      cytomegalovirus were below the median value of uninfected controls and similar in
      patients with R5, X4, or mixed infection. Interleukin-5 responses were low and
      plasma soluble CD30 levels were high at treatment onset, but resolved with
      control of HIV replication irrespective of HIV tropism. Levels of LAG-3
      (lymphocyte activation gene-3 protein) were elevated in patients with
      uncontrolled HIV replication. Hence the immunological milieu did not reflect HIV
      tropism.

PMID- 17201670
TI  - Transcriptional analysis of host responses to Marek's disease viral infection.
AB  - This study was aimed at investigating the genes that control host responses to
      Marek's disease virus (MDV). Spleen tissues from infected and age-matched
      uninfected control chickens were examined 4, 7, 14, and 21 d postinfection for
      gene expression differences, using both microarray and quantitative real-time
      polymerase chain reaction (PCR) methodologies. Up to 51% of genes assayed during
      microarray analysis showed a significant change (p < or = 0.05) in expression
      after MDV infection, of which cell surface molecules, transcription and signal
      transduction molecules, housekeeping and metabolism mediators, and cytokines and
      cytokine receptors were most commonly differentially expressed. Setting a fold
      change threshold (> or =2), 14 of 84 genes showed differential expression over
      time. In addition, some genes showed differential expression at more than one
      time point. For example, the granzyme-A homolog gene remained upregulated in
      infected chickens, with fold changes of 7.98, 13.91, and 9.07 at 7, 14, and 21 d
      postinfection, respectively. Other genes that were differentially expressed at
      more than one time point were invariant chain, IgM, and CD3. Quantitative real
      time PCR analysis was used to validate microarray results for a subset of genes
      showing a :2-fold change in expression. Expression of all but one gene (CD28) was
      confirmed. Identification of genetic mechanisms initiated by in vivo infection
      with MDV expands the current understanding of immune response to the virus in
      addition to host response elements associated with viral pathogenesis.

PMID- 17201669
TI  - Herpes simplex virus type 1 induction of chemokine production is unrelated to
      viral load in the cornea but not in the nervous system.
AB  - Herpes simplex virus type 1 elicits a strong host inflammatory response after
      corneal infection. The purpose of the current study was to compare the production
      of chemokines induced by viral infection at sites known to harbor virus after
      ocular inoculation in order to determine the relationship between viral load and
      chemokine expression. Using highly resistant IFN-alpha1 transgenic mice whose
      transgene is under the control of the glial fibrillary acidic protein promoter in
      comparison with the more sensitive wild-type counterparts, we compared the
      expression of chemokines versus the amount of infectious virus recovered from the
      anterior segment of the eye and nervous system. Consistent with our predicted
      outcome, the level of infectious virus recovered in the iris, trigeminal ganglia,
      and brainstem of resistant versus sensitive mice correlated with chemokine
      production; that is, the less virus recovered the less chemokine (CCL2, CCL3,
      CCL5, CXCL9, and CXCL10) produced. In contrast to the nervous system and iris,
      there was no correlation between chemokine expression and level of infectious
      virus recovered in the cornea. We interpret these results as suggesting chemokine
      expression within the cornea in response to herpes simplex virus type 1 infection
      is driven by factors other than antigenic stimulation.

PMID- 17201671
TI  - Immunovirologic characteristics of human immunodeficiency virus-infected patients
      consisting mainly of injecting drug users on highly active antiretroviral
      treatment with prolonged virologic failure.
AB  - Immunovirologic parameters of 24 heavily antiretroviral drug-pretreated patients
      with prolonged virologic treatment failure under highly active antiretroviral
      therapy, and who harbored highly resistant human immunodeficiency virus (HIV)
      isolates, were studied in this retrospective cross-sectional study. Most of the
      patients were injecting drug users (71%) and male (88%). All patients were
      studied for CD4(+) cell count, HIV viral load, resistance mutations, and viral
      phenotype. The patients showed a high accumulation of resistance-associated
      mutations, their CD4(+) cell count and viral load directly correlated with their
      respective values at initiation of therapy, and the presence of K103N was
      inversely associated with lower viral load. On the other hand, patients with
      K103N had the same level of CD4(+) cell count compared with patients without this
      mutation. Among the patients, a majority with a specific viral phenotype was not
      present. Rather, a dual-tropic virus was found most frequently, suggesting a
      preferential suppression of X4-specific strains and less cytopathogenicity during
      antiretroviral therapy and a greater proportion of R5X4 viruses due to an
      adaptation to that pressure.

PMID- 17201672
TI  - Transcriptome of local innate and adaptive immunity during early phase of
      infectious bronchitis viral infection.
AB  - To understand the mechanistic basis of local innate and adaptive immunity against
      infectious bronchitis virus (IBV) at the molecular level, we examined the gene
      transcription profile of tracheal epithelial layers 3 d after infection of
      chickens with an attenuated IBV-Massachusetts strain. Results suggested that the
      transcription levels of 365 genes were either upregulated or downregulated (2
      fold and higher) after IBV infection. Among the upregulated 250 genes, 25 were
      directly immune-related genes. These upregulated immune response genes included
      TLR2, TLR3, interferon-induced antiviral genes (Mx), and genes responsible for
      cytotoxic T cell killing such as Fas antigen and granzyme-A. Overall, a diversity
      of innate immunity and helper T cell type 1 (Th1)-biased adaptive immunity are
      activated in the host's early defense against IBV invasion, and they are
      responsible for the rapid clearance of virus from the local infection.

PMID- 17201674
TI  - Visualizing flexibility at molecular resolution: analysis of heterogeneity in
      single-particle electron microscopy reconstructions.
AB  - It is becoming increasingly clear that many macromolecules are intrinsically
      flexible and exist in multiple conformations in solution. Single-particle
      reconstruction of vitrified samples (cryo-electron microscopy, or cryo-EM) is
      uniquely positioned to visualize this conformational flexibility in its native
      state. Although heterogeneity remains a significant challenge in cryo-EM single
      particle analysis, recent efforts in the field point to a future where it will be
      possible to tap into this rich source of biological information on a routine
      basis. In this article, we review the basic principles behind a few relatively
      new and generally applicable methods that show particular promise as tools to
      analyze macromolecular flexibility. We also discuss some of their recent
      applications to problems of biological interest.

PMID- 17201675
TI  - Phase boundaries and biological membranes.
AB  - Bilayer mixtures of lipids are used by many researchers as chemically simple
      models for biological membranes. In particular, observations on three-component
      bilayer mixtures containing cholesterol show rich phase behavior, including
      several regions of two-phase coexistence and one region of three-phase
      coexistence. Yet, the relationship between these simple model mixtures and
      biological membranes, which contain hundreds of different proteins and lipids, is
      not clear. Many of the model mixtures have been chosen for study because they
      exhibit readily observed phase separations, not because they are good mimics of
      cell membrane components. If the many components of cell membranes could be
      grouped in some way, then understanding the phase behaviors of biological
      membranes might be enhanced. Furthermore, if the underlying interaction energies
      between lipids and proteins can be determined, then it might be possible to model
      the distributions of lipids and proteins in a bilayer membrane, even in complex
      mixtures.

PMID- 17201676
TI  - Calculation of protein-ligand binding affinities.
AB  - Accurate methods of computing the affinity of a small molecule with a protein are
      needed to speed the discovery of new medications and biological probes. This
      paper reviews physics-based models of binding, beginning with a summary of the
      changes in potential energy, solvation energy, and configurational entropy that
      influence affinity, and a theoretical overview to frame the discussion of
      specific computational approaches. Important advances are reported in modeling
      protein-ligand energetics, such as the incorporation of electronic polarization
      and the use of quantum mechanical methods. Recent calculations suggest that
      changes in configurational entropy strongly oppose binding and must be included
      if accurate affinities are to be obtained. The linear interaction energy (LIE)
      and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are
      analyzed, as are free energy pathway methods, which show promise and may be ready
      for more extensive testing. Ultimately, major improvements in modeling accuracy
      will likely require advances on multiple fronts, as well as continued validation
      against experiment.

PMID- 17201677
TI  - IL-17 family cytokines and the expanding diversity of effector T cell lineages.
AB  - Since its conception two decades ago, the Th1-Th2 paradigm has provided a
      framework for understanding T cell biology and the interplay of innate and
      adaptive immunity. Naive T cells differentiate into effector T cells with
      enhanced functional potential for orchestrating pathogen clearance largely under
      the guidance of cytokines produced by cells of the innate immune system that have
      been activated by recognition of those pathogens. This secondary education of
      post-thymic T cells provides a mechanism for appropriately matching adaptive
      immunity to frontline cues of the innate immune system. Owing in part to the
      rapid identification of novel cytokines of the IL-17 and IL-12 families using
      database searches, the factors that specify differentiation of a new effector T
      cell lineage-Th17-have now been identified, providing a new arm of adaptive
      immunity and presenting a unifying model that can explain many heretofore
      confusing aspects of immune regulation, immune pathogenesis, and host defense.

PMID- 17201678
TI  - Ontogeny of the hematopoietic system.
AB  - Blood cells are constantly produced in the bone marrow (BM) of adult mammals.
      This constant turnover ultimately depends on a rare population of progenitors
      that displays self-renewal and multilineage differentiation potential, the
      hematopoietic stem cells (HSCs). It is generally accepted that HSCs are generated
      during embryonic development and sequentially colonize the fetal liver, the
      spleen, and finally the BM. Here we discuss the experimental evidence that argues
      for the extrinsic origin of HSCs and the potential locations where HSC generation
      might occur. The identification of the cellular components playing a role in the
      generation process, in these precise locations, will be important in
      understanding the molecular mechanisms involved in HSC production from
      undifferentiated mesoderm.

PMID- 17201679
TI  - The death domain superfamily in intracellular signaling of apoptosis and
      inflammation.
AB  - The death domain (DD) superfamily comprising the death domain (DD) subfamily, the
      death effector domain (DED) subfamily, the caspase recruitment domain (CARD)
      subfamily, and the pyrin domain (PYD) subfamily is one of the largest domain
      superfamilies. By mediating homotypic interactions within each domain subfamily,
      these proteins play important roles in the assembly and activation of apoptotic
      and inflammatory complexes. In this chapter, we review the molecular complexes
      assembled by these proteins, the structural and biochemical features of these
      domains, and the molecular interactions mediated by them. By analyzing the
      potential molecular basis for the function of these domains, we hope to provide a
      comprehensive understanding of the function, structure, interaction, and
      evolution of this important family of domains.

PMID- 17201680
TI  - The host defense of Drosophila melanogaster.
AB  - To combat infection, the fruit fly Drosophila melanogaster relies on multiple
      innate defense reactions, many of which are shared with higher organisms. These
      reactions include the use of physical barriers together with local and systemic
      immune responses. First, epithelia, such as those beneath the cuticle, in the
      alimentary tract, and in tracheae, act both as a physical barrier and local
      defense against pathogens by producing antimicrobial peptides and reactive oxygen
      species. Second, specialized hemocytes participate in phagocytosis and
      encapsulation of foreign intruders in the hemolymph. Finally, the fat body, a
      functional equivalent of the mammalian liver, produces humoral response molecules
      including antimicrobial peptides. Here we review our current knowledge of the
      molecular mechanisms underlying Drosophila defense reactions together with
      strategies evolved by pathogens to evade them.

PMID- 17201682
TI  - Fc receptor-like molecules.
AB  - Discovery of a large family of Fc receptor-like (FCRL) molecules, homologous to
      the well-known receptors for the Fc portion of immunoglobulin (FCR), has
      uncovered an impressive abundance of immunoglobulin superfamily (IgSF) genes in
      the human 1q21-23 chromosomal region and revealed significant diversity for these
      genes between humans and mice. The observation that FCRL representatives are
      members of an ancient multigene family that share a common ancestor with the
      classical FCR is underscored by their linked genomic locations, gene structure,
      shared extracellular domain composition, and utilization of common cytoplasmic
      tyrosine-based signaling elements. In contrast to the conventional FCR, however,
      FCRL molecules possess diverse extracellular frameworks, autonomous or dual
      signaling properties, and preferential B lineage expression. Most importantly,
      there is no strong evidence thus far to support a role for them as Ig-binding
      receptors. These characteristics, in addition to their identification in
      malignancies and autoimmune disorders, predict a fundamental role for these
      receptors as immunomodulatory agents in normal and subverted B lineage cells.

PMID- 17201684
TI  - Exciton photophysics of carbon nanotubes.
AB  - The goal of this chapter is to review the importance of excitons to single-wall
      carbon nanotube (SWNT) optics. We have developed the presentation for both
      researchers in the SWNT field who want to learn more about the unusual aspects of
      SWNT exciton photophysics and researchers more knowledgeable about the physics of
      excitons, but not about SWNT physics. Excitons in SWNTs are special because
      graphite has two energy bands at the Fermi energy related to time-reversal
      symmetry and because SWNTs are actually one dimensional. This review discusses
      both theoretical and experimental points of view, thus aiming to provide a
      summary of the most important work in the field, as well as to identify open
      questions.

PMID- 17201683
TI  - Regulation of cellular and humoral immune responses by the SLAM and SAP families
      of molecules.
AB  - SAP (SLAM-associated protein) was identified in 1998 as an adaptor molecule
      involved in the intracellular signaling pathways elicited through the cell
      surface receptor SLAM and as the protein defective in the human immunodeficiency
      X-linked lymphoproliferative disease (XLP). During the past eight years, it has
      been established that the SLAM family of cell surface receptors (SLAM, 2B4, NTB
      A, Ly9, CD84) and the SAP family of adaptors (SAP, EAT-2, ERT) play critical
      roles in lymphocyte development, differentiation, and acquisition of effector
      functions. Studies of these proteins have shown unexpected roles in cytokine
      production by T cells and myeloid cells, T cell-dependent humoral immune
      responses, NK cell-mediated cytotoxicity, and NKT cell development. This review
      highlights recent findings that have improved our understanding of the roles of
      the SLAM and SAP families of molecules in immune regulation and discusses how
      perturbations in the signaling pathways involving these proteins can result in
      different disease states.

PMID- 17201681
TI  - Structural basis of integrin regulation and signaling.
AB  - Integrins are cell adhesion molecules that mediate cell-cell, cell-extracellular
      matrix, and cell-pathogen interactions. They play critical roles for the immune
      system in leukocyte trafficking and migration, immunological synapse formation,
      costimulation, and phagocytosis. Integrin adhesiveness can be dynamically
      regulated through a process termed inside-out signaling. In addition, ligand
      binding transduces signals from the extracellular domain to the cytoplasm in the
      classical outside-in direction. Recent structural, biochemical, and biophysical
      studies have greatly advanced our understanding of the mechanisms of integrin
      bidirectional signaling across the plasma membrane. Large-scale reorientations of
      the ectodomain of up to 200 A couple to conformational change in ligand-binding
      sites and are linked to changes in alpha and beta subunit transmembrane domain
      association. In this review, we focus on integrin structure as it relates to
      affinity modulation, ligand binding, outside-in signaling, and cell surface
      distribution dynamics.

PMID- 17201685
TI  - Stomatal development.
AB  - Stomata are cellular epidermal valves in plants central to gas exchange and
      biosphere productivity. The pathways controlling their formation are best
      understood for Arabidopsis thaliana where stomata are produced through a series
      of divisions in a dispersed stem cell compartment. The stomatal pathway is an
      accessible system for analyzing core developmental processes including position
      dependent patterning via intercellular signaling and the regulation of the
      balance between proliferation and cell specification. This review synthesizes
      what is known about the mechanisms and genes underlying stomatal development. We
      contrast the functions of genes that act earlier in the pathway, including
      receptors, kinases, and proteases, with those that act later in the cell lineage.
      In addition, we discuss the relationships between environmental signals, stomatal
      development genes, and the capacity for controlling shoot gas exchange.

PMID- 17201686
TI  - The biology of arabinogalactan proteins.
AB  - Arabinogalactan proteins is an umbrella term applied to a highly diverse class of
      cell surface glycoproteins, many of which contain glycosylphosphatidylinositol
      lipid anchors. The structures of protein and glycan moieties of arabinogalactan
      proteins are overwhelmingly diverse while the "hydroxproline contiguity
      hypothesis" predicts arabinogalactan modification of members of many families of
      extracellular proteins. Descriptive studies using monoclonal antibodies reacting
      with carbohydrate epitopes on arabinogalactan proteins and experimental work
      using beta-Yariv reagent implicate arabinogalactan proteins in many biological
      processes of cell proliferation and survival, pattern formation and growth, and
      in plant microbe interaction. Advanced structural understanding of
      arabinogalactan proteins and an emerging molecular genetic definition of
      biological roles of individual arabinogalactan protein species, in conjunction
      with potentially analogous extracellular matrix components of animals, stimulate
      hypotheses about their mode of action. Arabinogalactan proteins might be soluble
      signals, or might act as modulators and coreceptors of apoplastic morphogens;
      their amphiphilic molecular nature makes them prime candidates of mediators
      between the cell wall, the plasma membrane, and the cytoplasm.

PMID- 17201687
TI  - Quality improvement in public health emergency preparedness.
AB  - Quality improvement (QI) methods have been used in many industries to improve
      performance and outcomes. This chapter reviews key QI concepts and their
      application to public health emergency preparedness (PHEP). We conclude that for
      QI to flourish and become standard practice, changes to the status quo are
      necessary. In particular, public health should build its capabilities in QI,
      enhance implementation, and align incentives to facilitate use of QI.

PMID- 17201689
TI  - Cyclic electron transport around photosystem I: genetic approaches.
AB  - The light reactions in photosynthesis convert light energy into chemical energy
      in the form of ATP and drive the production of NADPH from NADP+. The reactions
      involve two types of electron flow in the chloroplast. While linear electron
      transport generates both ATP and NADPH, photosystem I cyclic electron transport
      is exclusively involved in ATP synthesis. The physiological significance of
      photosystem I cyclic electron transport has been underestimated, and our
      knowledge of the machineries involved remains very limited. However, recent
      genetic approaches using Arabidopsis thaliana have clarified the essential
      functions of this electron flow in both photoprotection and photosynthesis. Based
      on several lines of evidence presented here, it is necessary to reconsider the
      fundamental mechanisms of chloroplast energetics.

PMID- 17201690
TI  - The plant heterotrimeric G-protein complex.
AB  - Heterotrimeric G-protein complexes couple extracellular signals via cell surface
      receptors to downstream enzymes called effectors. Heterotrimeric G-protein
      complexes, together with their cognate receptors and effectors, operate at the
      apex of signal transduction. In plants, the number of G-protein complex
      components is dramatically less than in other multicellular eukaryotes. An
      understanding of how multiple signals propagate transduction through the G
      protein node can be found in the unique structural and kinetic properties of the
      plant heterotrimeric G-protein complex. This review addresses these unique
      features and speculates on why the repertoire of G-protein signaling elements is
      dramatically simpler than that in all other multicellular eukaryotes.

PMID- 17201692
TI  - Insulin-mimetic and insulin-sensitizing activities of a pentacyclic triterpenoid
      insulin receptor activator.
AB  - Five pentacyclic triterpenoids isolated from Campsis grandiflora were tested for
      insulin-mimetic and insulin-sensitizing activity. The compounds enhanced the
      activity of insulin on tyrosine phosphorylation of the IR (insulin receptor) beta
      subunit in CHO/IR (Chinese-hamster ovary cells expressing human IR). Among the
      compounds tested, CG7 (ursolic acid) showed the greatest enhancement and CG11
      (myrianthic acid) the least. We characterized the effect of CG7 further, and
      showed that it acted as an effective insulin-mimetic agent at doses above 50
      mug/ml and as an insulin-sensitizer at doses as low as 1 mug/ml. Additional
      experiments showed that CG7 increased the number of IRs that were activated by
      insulin. This indicates that a major mechanism by which CG7 enhances total IR
      auto-phosphorylation is by promoting the tyrosine phosphorylation of additional
      IRs. CG7 not only potentiated insulin-mediated signalling (tyrosine
      phosphorylation of the IR beta-subunit, phosphorylation of Akt and glycogen
      synthase kinase-3beta), but also enhanced the effect of insulin on translocation
      of glucose transporter 4 in a classical insulin-sensitive cell line, 3T3-L1
      adipocytes. The results of the present study demonstrate that a specific
      pentacyclic triterpenoid, CG7, exerts an insulin-sensitizing effect as an IR
      activator in CHO/IR cells and adipocytes. The enhancement of insulin activity by
      CG7 may be useful for developing a new class of specific IR activators for
      treatment of Type 1 and Type 2 diabetes.

PMID- 17201693
TI  - Quaternary structure and biochemical properties of mycobacterial RNase E/G.
AB  - The RNase E/G family of endoribonucleases plays the central role in numerous post
      transcriptional mechanisms in Escherichia coli and, presumably, in other
      bacteria, including human pathogens. To learn more about specific properties of
      RNase E/G homologues from pathogenic Gram-positive bacteria, a polypeptide
      comprising the catalytic domain of Mycobacterium tuberculosis RNase E/G (MycRne)
      was purified and characterized in vitro. In the present study, we show that
      affinity-purified MycRne has a propensity to form dimers and tetramers in
      solution and possesses an endoribonucleolytic activity, which is dependent on the
      5'-phosphorylation status of RNA. Our data also indicate that the cleavage
      specificities of the M. tuberculosis RNase E/G homologue and its E. coli
      counterpart are only moderately overlapping, and reveal a number of sequence
      determinants within MycRne cleavage sites that differentially affect the
      efficiency of cleavage. Finally, we demonstrate that, similar to E. coli RNase E,
      MycRne is able to cleave in an intercistronic region of the putative 9S precursor
      of 5S rRNA, thus suggesting a common function for RNase E/G homologues in rRNA
      processing.

PMID- 17201694
TI  - An increase in plasma adiponectin multimeric complexes follows hypocaloric diet
      induced weight loss in obese and overweight pre-menopausal women.
AB  - Adiponectin is involved in the regulation of glucose and fatty acid metabolism,
      influences whole-body insulin sensitivity and protects arterial walls against the
      development of atherosclerosis. Plasma adiponectin is decreased in obese, insulin
      resistant and Type 2 diabetic patients. Adiponectin circulates in plasma as high
      , medium- and low-molecular-weight ('mass') forms (HMW, MMW and LMW
      respectively). The HMW form is believed to be closely associated with insulin
      sensitivity. The aim of the present study was to investigate whether diet-induced
      changes in body weight and insulin sensitivity were associated with changes in
      the quantity of adiponectin multimeric complexes. A total of 20 overweight or
      obese women (age, 39.4+/-9.5 years; body mass index, 32.2+/-6.4 kg/m(2))
      underwent 12 weeks of low caloric diet (600 kcal/day less than energy
      requirements; where 1 kcal is approximately 4.184 kJ). Plasma samples were drawn
      before and after the study for biochemical analysis and Western blot detection of
      adiponectin multimeric complexes. The hypocaloric diet resulted in a weight
      reduction (89.8+/-16.4 kg compared with 83.1+/-15.6 kg; P<0.001) and an
      improvement in whole-body insulin sensitivity, as measured by HOMA (homoeostasis
      model assessment index; 1.9+/-0.8 compared with 1.5+/-0.7; P=0.013). Increases in
      the quantities of the HMW, MMW and LMW forms by 5.5, 8.5 and 18.1% respectively,
      were observed (P<0.05 for all of the forms). Total plasma adiponectin was
      increased by 36% with borderline significance (P=0.08). No correlations between
      changes in adiponectin complexes and changes in indices of insulin sensitivity
      were observed. In conclusion, diet-induced weight loss improved insulin
      sensitivity as well as increased the amount of HMW, MMW and LMW adiponectin
      complexes in plasma.

PMID- 17201695
TI  - Electrolytes disturbances and seizures.

PMID- 17201696
TI  - Seizures and antiepileptic drugs: does exposure alter normal brain development?
AB  - Seizures and antiepileptic drugs (AEDs) affect brain development and have long
      term neurological consequences. The specific molecular and cellular changes, the
      precise timing of their influence during brain development, and the full extent
      of the long-term consequences of seizures and AEDs exposure have not been
      established. This review critically assesses both the basic and clinical science
      literature on the effects of seizures and AEDs on the developing brain and finds
      that evidence exists to support the hypothesis that both seizures and
      antiepileptic drugs influence a variety of biological process, at specific times
      during development, which alter long-term cognition and epilepsy susceptibility.
      More research, both clinical and experimental, is needed before changes in
      current clinical practice, based on the scientific data, can be recommended.

PMID- 17201697
TI  - Development of performance indicators for the primary care management of
      pediatric epilepsy: expert consensus recommendations based on the available
      evidence.
AB  - PURPOSE: To use available evidence and expert consensus to develop performance
      indicators for the evaluation and management of pediatric epilepsy. METHODS: We
      used a three-step process to develop the performance indicators. First, research
      findings were compiled into evidence tables focusing on different clinical
      issues. Second, an advisory panel of clinicians, educational and public health
      experts, and families of children with epilepsy reviewed the evidence. The
      advisory group used the evidence to draft a preliminary set of performance
      indicators for pediatric epilepsy management. Third, 13 internationally
      recognized experts in pediatric neurology or epilepsy rated the value of these
      indicators on a 5-point scale [1 (essential) to 5 (not necessary)] in a two-round
      Delphi process. Positive consensus was reached if >or=80% of experts gave an
      indicator a "1" rating and negative consensus if >80% gave an indicator a "5"
      rating. Indicators that achieved positive consensus during either round of the
      Delphi process constituted the final set of indicators. RESULTS: Of the 68 draft
      performance indicators, the expert panel members achieved positive consensus on
      30 performance indicators: eight indicators related to diagnostic strategies and
      seizure classification, nine related to antiepileptic drug use, six related to
      cognitive and behavioral issues, six related to quality of life, and three
      related to specialty referrals. CONCLUSIONS: We identified 30 potential
      indicators for evaluating the care provided to pediatric patients with epilepsy.
      The next step is to examine the relation of these performance indicators to
      clinical outcomes and health care utilization among pediatric patients with
      epilepsy.

PMID- 17201698
TI  - Status epilepticus after stroke is associated with increased long-term case
      fatality.
AB  - PURPOSE: The aim of this study was to determine the long-term case fatality of
      patients with a first episode of status epilepticus (SE group) of cerebrovascular
      etiology, as compared with that in acute stroke patients without SE (AS group).
      METHODS: Patients with SE who had been prospectively admitted to an epidemiologic
      study were retrospectively compared with a cohort of patients from the local
      stroke registry. The main outcome end point was overall survival. Survival curves
      were generated according to the Kaplan-Meier method and compared by using the log
      rank test. An extended Cox model was used to examine the impact of patient group
      on the risk of death. Covariates considered potential confounders included age at
      diagnosis, sex, type of stroke, affected hemisphere, and localization of lesions.
      RESULTS: Of 166 patients who entered the study, 93 patients were in the SE group,
      and 73 patients were in the AS group; 53 SE patients and 35 AS patients died
      during the study. Patient group (SE vs. AS) showed no significant impact on
      survival (p=0.0832) in univariate analysis. In contrast, the results from a
      multivariable analysis suggest that after 6 months, patients with SE were at
      about twice the risk of death as were patients with AS [hazard ratio of 2.12 with
      95% confidence interval, 1.04-4.32, p=0.0392]. CONCLUSIONS: The occurrence of SE
      in patients with cerebrovascular disease indicates a high risk of death within 3
      years. In contrast, the case fatality risk attributable to recurrent status or
      seizures is lower.

PMID- 17201699
TI  - Valproic acid-induced hepatopathy: nine new fatalities in Germany from 1994 to
      2003.
AB  - PURPOSE: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for
      generalized and focal epilepsies. We provide an update on hepatotoxic side
      effects in Germany between 1994 and 2003. METHODS: We mailed a questionnaire to
      all members of the German Section of the International League Against Epilepsy,
      asking for VPA-induced side effects, especially severe side effects such as
      hepatopathy. RESULTS: As a result of our questionnaire, we found 31 cases of
      reversible hepatotoxicity and nine cases of lethal hepatopathies in Germany from
      1994 to 2003. CONCLUSIONS: The outcome of patients with severe hepatotoxicity is
      better than that in the past. The risk of a VPA-induced hepatopathy is not
      limited to patients younger than 2 years, receiving polytherapy, or patients with
      congenital or acquired metabolic diseases.

PMID- 17201700
TI  - Assessing the disease burden due to epilepsy by disability adjusted life year in
      rural China.
AB  - PURPOSE: To demonstrate the application of Disability Adjusted Life Year (DALY)
      as an aid in health outcome measures to evaluate the epilepsy disease burden in
      rural China and to provide Chinese data to achieve a better understanding of
      disease burden due to epilepsy. METHODS: The DALY is the sum of the number of
      years of survival with disability (Years Lived with Disability, YLD) and the
      number of years lost because of premature mortality (Years of Life Lost, YLL). We
      calculated the YLD based on the prevalence survey of epilepsy among 66,393 people
      sampled in Heilongjiang, Henan, Jiangsu, Ningxia, Shanghai, and Shanxi provinces
      in 2000. The epilepsy mortality data from Chinese literature provided the YLL due
      to epilepsy. We applied sensitivity analysis to evaluate the influence of
      uncertainty on the epilepsy mortality value and disability weight in the study.
      RESULTS: In 2000, epilepsy caused 1.83 and 2.48 DALY lost per 1,000 population in
      Henan and Ningxia province, which had the lowest and the highest DALY lost among
      the six study areas. Overall, epilepsy caused 1.41 YLLs and 0.67 YLDs per 1,000
      population; thus the DALYs lost because of epilepsy was 2.08 per 1,000
      population, representing the epilepsy disease burden in rural China. CONCLUSIONS:
      The DALY measure, which includes the extent of disability from epilepsy, provides
      a useful tool for the epilepsy disease burden assessment. The disease burden of
      epilepsy in China is considered higher than previous estimations.

PMID- 17201701
TI  - Influence of major antiepileptic drugs on attention, reaction time, and speed of
      information processing: results from a randomized, double-blind, placebo
      controlled withdrawal study of seizure-free epilepsy patients receiving
      monotherapy.
AB  - PURPOSE: All major antiepileptic drugs (AEDs) have been reported to be associated
      with cognitive side effects. Uncertainty exists regarding the degree of cognitive
      effects, primarily because many studies do not adhere to basic standards of
      methodology and design. The aim of this study was to assess the effect of
      discontinuation of AEDs in patients receiving monotherapy on measures of
      attention, reaction time, and speed of information processing. METHODS: The 150
      subjects who had been seizure free>2 years on drug monotherapy went through a
      randomized, double-blind, placebo-controlled study. Each patient was included for
      12 months or until seizure relapse. Cognitive function was assessed with the
      California Computerized Assessment Package at baseline and 7 months after
      discontinuation. RESULTS: The major finding in this study is that discontinuation
      of major AEDs significantly improved performance on tests that require complex
      cognitive processing under time pressure. The difference in speed of cognitive
      processing between the two groups on these tasks was between 24 to 43 ms. Simple
      tasks of attention and reaction time revealed no significant differences between
      the discontinuation group and the nondiscontinuation group. Most of the subjects
      in the study were medicated with carbamazepine (CBZ) and valproate (VPA). The
      outcome of discontinuation of CBZ was similar to the outcome for the total study
      population, whereas withdrawal of VPA revealed only a nonsignificant tendency in
      the same direction. CONCLUSIONS: The results suggest that seizure-free epilepsy
      patients receiving monotherapy can obtain improvement in cognitive function if
      they discontinue AED treatment.

PMID- 17201702
TI  - Postictal but not interictal hemispatial neglect in patients with seizures of
      lateralized onset.
AB  - PURPOSE: Unilateral spatial neglect, defined as a failure to report, respond, or
      orient to stimuli that are presented contralaterally, has been widely documented
      after brain damage to right, and to a lesser degree, left frontotemporoparietal
      networks. Group studies involving patients with seizures with a lateralized focus
      have demonstrated transient dysfunctions in memory and language; however, so far,
      only two case reports have described transient neglect after an epileptic
      seizure. METHODS: To assess the existence and consistency of this phenomenon, we
      evaluated 33 epilepsy patients on a line-bisection task in interictal and
      postictal states as compared with an age- and sex-matched control group. RESULTS:
      Spatial neglect, as determined by this test, was found in the postictal but not
      interictal examination in patients with right parietal epileptic foci and was
      maximal for the left-positioned lines, whereas no neglect was found in other
      groups. CONCLUSIONS: Our findings indicate that patients with right parietal foci
      can present a transient neglect phenomenon on the line-bisection task in the
      postictal period, even in the absence of overt clinical neglect signs. These
      findings might be useful in establishing the laterality and even localization of
      epileptic foci based on the postictal neuropsychological evaluation.

PMID- 17201703
TI  - Epilepsy and the impact of an epileptology clinic for patients with mental
      retardation and associated disabilities in an institutional setting.
AB  - PURPOSE: Epilepsy is a common problem in institutionalized patients with multiple
      handicaps. Limited data exist on the characteristics of epilepsy in this patient
      population and the impact of systematic evaluation by an epilepsy service.
      METHODS: We evaluated 138 patients with epilepsy, institutionalized at a facility
      that cares for 324 patients with multiple handicaps. Evaluation included EEG,
      MRI, and video-EEG monitoring. The medication regimen was changed according to
      seizure diagnosis and the status of seizure control. Follow-up was available for
      >or=6 months in 110 patients, 1 year for 89, and 1.5 years for 49 patients. We
      analyzed the seizure and epilepsy diagnosis in this population, as well as the
      seizure frequency after evaluation and treatment. RESULTS: The 76 male and 62
      female patients' ages ranged from 14 to 73 years. Seventy-three patients had
      fewer than one seizure per month, whereas 29 patients had at least one seizure
      per month. Of 131 patients taking antiepileptic drugs (AEDs), 62 were receiving
      monotherapy, and 69 were receiving two or more AEDs. At the last follow-up,
      overall 55% of patients had reduced seizure frequency, including 23% who became
      seizure free. Two of 36 patients had spontaneous seizure recurrence after being
      seizure free with no AEDs for 4 months in one patient and 3 years for the other.
      Attempts were made to discontinue phenobarbital, primidone, and clonazepam in 21
      patients. However, these were discontinued in only five patients. CONCLUSIONS:
      Epilepsy is heterogeneous in institutionalized patients with multiple handicaps.
      It is often responsive to medical therapy. Evaluation and treatment by epilepsy
      specialists had an overall favorable impact on seizure control.

PMID- 17201704
TI  - Do false predictions of seizures depend on the state of vigilance? A report from
      two seizure-prediction methods and proposed remedies.
AB  - PURPOSE: Available seizure-prediction algorithms are accompanied by high numbers
      of false predictions to achieve high sensitivity. Little is known about the
      extent to which changes in EEG dynamics contribute to false predictions. This
      study addresses potential causes and the circadian distribution of false
      predictions as well as their relation to the sleep-wake cycle. METHODS: In 21
      patients, each with 24 h of interictal invasive EEG recordings, two methods, the
      dynamic similarity index and the mean phase coherence, were assessed with respect
      to time points of false predictions. Visual inspection of the invasive EEG data
      and additional scalp electroencephalogram data was performed at times of false
      predictions to identify possible correlates of changes in the EEG dynamics.
      RESULTS: A dependency of false predictions on the time of day is shown.
      Renormalized to the duration of the period patients are asleep and awake, 86% of
      all false predictions occurred during sleep for the dynamic similarity index and
      68% for the mean phase coherence, respectively. Combining two reference
      intervals, one during sleep and one in an awake state, the dynamic similarity
      index increases its performance by reducing the number of false predictions by
      almost 50% without major changes in sensitivity. No obvious dependence of false
      predictions was noted on visible epileptic activity, such as spikes, sharp waves,
      or subclinical ictal patterns. CONCLUSIONS: Changes in the EEG dynamics related
      to the sleep-wake cycle contribute to limits of specificity of both seizure
      prediction methods investigated. This may provide a clue for improving prediction
      methods in general. The combination of reference states yields promising results
      and may offer opportunities to increase further the performance of prediction
      methods.

PMID- 17201705
TI  - Lithium-induced confusional states: nonconvulsive status epilepticus or triphasic
      encephalopathy?
AB  - Lithium therapy can cause a confusional state by direct toxicity, precipitation
      of nonconvulsive status epilepticus, or by interplay with other neuroleptic
      medications to produce neuroleptic malignant syndrome or serotonin syndrome.
      These conditions resemble each other clinically, but EEG may help differentiate
      among them. We reviewed the EEG patterns with triphasic waves or rhythmic delta
      activity in lithium toxic patients and discuss clinical and EEG differentiation
      among syndromes. Lithium toxicity poses significant diagnostic challenges from
      EEG and clinical perspectives.

PMID- 17201707
TI  - Lack of efficacy and potential aggravation of myoclonus with lamotrigine in
      Unverricht-Lundborg disease.
AB  - PURPOSE: Unverricht-Lundborg disease (ULD) is a progressive myoclonus epilepsy
      with tonic-clonic seizures, action myoclonus, mild ataxia, without dementia.
      Persistence of invalidating action myoclonus is a major problem. Drugs like
      phenytoin can aggravate ULD. In this study, we retrospectively analyzed the
      effect of add-on lamotrigine (LTG) in the five patients under our care who
      received LTG. METHOD: Three men and two women, aged 20-50 years who had ULD
      confirmed by molecular biology, followed in two epilepsy centers, received add-on
      LTG at 50-300 mg/d. All of them had valproate. The other drugs used in cotherapy
      were high-dose piracetam, benzodiazepines phenobarbital, topiramate, and
      primidone. The assessment of LTG was based on detailed interview and clinical
      examination. Aggravation was diagnosed when myoclonic jerks (MJ) increased
      without irregular intake of medication, inappropriate lifestyle, encephalopathic
      or metabolic complications, or overdosage. RESULTS: In two patients, LTG
      exacerbated MJ in a dose-dependent manner. In one patient, a delayed, severe
      exacerbation of myoclonus occurred that only ceased after LTG withdrawal and
      introduction of levetiracetam. These three patients had minor forms of ULD. In
      two patients with moderate to severe forms of ULD, LTG had no effect. CONCLUSION:
      Although symptoms may fluctuate in ULD, it was possible to pinpoint lack of
      improvement (2/5), dose-related exacerbation of myoclonus (2/5), and putative
      late-onset aggravation (1/5) in five patients treated with adjunctive LTG. LTG
      does not appear to be a sensible treatment option in ULD.

PMID- 17201706
TI  - Pentylenetetrazole kindling affects sleep in rats.
AB  - PURPOSE: The aim of the study was to define sleep disturbances in
      pentylenetetrazole (PTZ)-kindled rats and to explore the effects of the nootropic
      drug piracetam (Pir; 100 mg/kg) and the noncompetitive N-methyl-D-aspartate
      (NMDA)-antagonist MK-801 (0.3 mg/kg), which normalized learning performance in
      PTZ-kindled rats, on altered sleep parameters. METHODS: This is the first report
      showing a significant reduction in paradoxical sleep (PS) as a consequence of PTZ
      kindling. A correlation analysis revealed a significant correlation between
      seizure severity and PS deficit. RESULTS: Pir did not interfere with seizure
      severity, and the substance did not ameliorate the PS deficit. However, the
      substance disconnected the correlation between seizure severity and PS deficit.
      MK-801, which reduced the severity of kindled seizures, counteracted the PS
      deficit efficaciously. CONCLUSIONS: The results suggest that seizure severity and
      alterations in sleep architecture are two factors in the comprehensive network
      underlying learning impairments associated with epilepsy. Considering the results
      obtained in the experiments with Pir, reduction of seizure severity does not
      guarantee the reduction of impairments in the domain of learning.

PMID- 17201708
TI  - Psychiatric comorbidity in juvenile myoclonic epilepsy.
AB  - OBJECTIVE: To assess the prevalence of psychiatric disturbances among patients
      with juvenile myoclonic epilepsy (JME). METHODS: Forty-three patients with JME
      (22 female, 21 male, mean age 32.4+/-13, range 15-63) were assessed by means of
      the Structured Clinical Interviews for DSM-IV (SCID-I and SCID-II). Current and
      lifetime psychiatric diagnoses were assigned. RESULTS: Thirty-five percent of the
      JME patients suffered from one or more psychiatric disorders (Axis I and Axis
      II). Personality disorders were present in 23% and Axis I disorders in 19%.
      Altogether, 47% had a psychiatric disorder at any time of their life.
      CONCLUSIONS: Psychiatric diagnoses are slightly higher than in representative
      community samples. The substantially increased number of personality disorders in
      JME patients might be attributed to frontal lobe deficits.

PMID- 17201709
TI  - Interictal depression, anxiety, personality traits, and psychological
      dissociation in patients with temporal lobe epilepsy (TLE) and extra-TLE.
AB  - PURPOSE: This study was performed to investigate the relation between symptoms of
      interictal depression, anxiety, personality traits, and psychological
      dissociation with the localization and lateralization of the epileptogenic zone
      in patients with partial epilepsy. METHODS: All patients were diagnosed according
      to the localization-related concept of the 1989 International League Against
      Epilepsy (ILAE) Classification of Epilepsies and Epileptic Syndromes, and the
      localization and lateralization of the epileptogenic zone was established by
      using the clinical criteria for noninvasive presurgical evaluation. This resulted
      in 67 patients with temporal lobe epilepsy (TLE) and 64 patients with extra-TLE.
      All patients were assessed on the various aspects of psychopathology by using a
      comprehensive battery of standardized diagnostic instruments. RESULTS: We did not
      find the hypothesized excess of psychiatric symptoms in patients with (mesial)
      TLE in comparison with patients with extra-TLE. We also found no differences
      between patients with the lateralization of epilepsy in the left versus the right
      hemisphere. CONCLUSIONS: TLE per se cannot be considered a risk factor in
      developing more or more severe symptoms of psychopathology in patients with
      partial epilepsy. Concomitant factors, such as the duration of epilepsy, seizure
      frequency, and frontal lobe dysfunction may play an additional role. Our findings
      support the hypothesis of a multifactorial explanation for the psychiatric
      symptoms in patients with epilepsy.

PMID- 17201710
TI  - Postictal mania versus postictal psychosis: differences in clinical features,
      epileptogenic zone, and brain functional changes during postictal period.
AB  - PURPOSE: To clarify the differences between postictal mania (PIM) and postictal
      psychosis (PIP). METHODS: Five patients with PIM were compared to 17 patients
      with PIP, with respect to clinical, epileptological, electrophysiological, and
      neuroimaging features. PIM was distinguished from PIP by the symptoms observed in
      the postictal period based on the ICD-10 criteria. RESULTS: Postictal manic
      episodes lasted for a longer period than postictal psychotic episodes. Patients
      with PIM had more recurrent postictal episodes than patients with PIP. The age at
      onset of epilepsy in patients with PIM was older than that in patients with PIP.
      PIM was associated with frontal lobe and temporal lobe epilepsies, whereas PIP
      was associated with temporal lobe epilepsy. The estimated epileptogenic zone was
      on the language dominant side in PIM, whereas there was no predominant
      hemispheric laterality in PIP. Electroencephalography (EEG) performed during the
      early period of postictal manic and psychotic episodes showed decreased frequency
      of interictal epileptiform discharges in both PIM and PIP. Single-photon emission
      computed tomography (SPECT) during postictal manic and psychotic episodes showed
      increased perfusion in the temporal and/or frontal lobes in both PIM and PIP.
      Three patients with PIM showed increased perfusion during postictal episodes on
      bilateral or the language nondominant side, which were contralateral to the
      estimated epileptogenic zone, whereas three patients with PIP showed increased
      perfusion on the areas, which were ipsilateral to the estimated epileptogenic
      zone. CONCLUSIONS: PIM has a distinct position among the mental disorders
      observed in the postictal period.

PMID- 17201711
TI  - Long-term prognosis and psychosocial outcomes after surgery for MTLE.
AB  - PURPOSE: To assess the seizure-freedom rates and self-perceived psychosocial
      changes associated with the long-term outcome of epilepsy surgery in patients
      with refractory medial temporal lobe epilepsy associated with hippocampal
      sclerosis. METHODS: A standard questionnaire was given to 183 patients who
      underwent surgery between 1988 and 2004, and 110 were completed. RESULTS: The
      mean duration of follow-up after surgery was 7 years, with a maximum of 17 years.
      The probability that patients were seizure-free after surgery was dependent on
      the definition of the seizure freedom. For the patients who were seizure-free
      since surgery (Engel's class Ia), the probability was 97.6% at 1 year after
      surgery, 85.2% at 2 years after surgery, 59.5% at 5 years after surgery, and
      42.6% at 10 years after surgery. For the patients who still experienced rare
      disabling seizures after surgery but were seizure-free at least 1 year before the
      time of assessment, the probability was of 97.6% at 1 year after surgery, 95% at
      2 years after surgery, 82.8% at 5 years after surgery, and 71.1% at 10 years
      after surgery. The psychosocial long-term outcome, as measured by indices of
      driving, employment, familial and social relationships, and marital status, was
      similar to the psychosocial short-term outcome. It did not depend on seizure
      freedom or on follow-up time interval and was not influenced statistically by
      seizure frequency in cases of persisting seizures. Most but not all patients
      noticed a substantial overall improvement in their psychosocial condition; 48%
      drove (increased by 7%), 47% improved (14% worsened) in their employment status,
      and 68% improved (5% worsened) in their familial and social relationships.
      Overall, 91% of patients were satisfied with the surgery, and 92% did not regret
      their decision. CONCLUSIONS: The results of this study suggest that temporal lobe
      surgery has real long-term benefits. Two specific conclusions emerge: (a) the
      long-term rates of freedom from seizure depend on how seizure freedom is defined,
      and (b) the psychosocial long-term outcome does not change dramatically over
      years and does not depend on seizure freedom.

PMID- 17201712
TI  - Depression in temporal lobe epilepsy surgery patients: an FDG-PET study.
AB  - PURPOSE: Depression is common in temporal lobe epilepsy (TLE) and after temporal
      lobectomy, and its etiology is obscure. In nonepileptic depression (including
      depression associated with other neurologic disorders), a consistent PET imaging
      finding is frontal lobe hypometabolism. Many TLE patients have hypometabolism
      involving frontal regions. Thus in data available from routine clinical
      assessments in an epilepsy surgery unit, we tested the hypothesis that the
      pattern of hypometabolism, particularly in the frontal lobe, may be associated
      with the depression seen in patients with TLE and TLE surgery. METHODS: We
      studied 23 medically refractory TLE patients who underwent anterior temporal
      lobectomy and who had preoperative FDG-PET scanning. All patients had pre- and
      postoperative psychiatric assessment. By using statistical parametric mapping
      (SPM-99), patterns of hypometabolism were compared between patients who had a
      preoperative history of depression (n=9) versus those who did not (n=14) and
      between those in whom postoperative depression developed (n=13) versus those in
      whom it did not (n=10). A significant region of hypometabolism was set at p<0.001
      for a cluster of >or=20 contiguous voxels. RESULTS: Patients with a history of
      depression at any time preoperatively showed focal hypometabolism in ipsilateral
      orbitofrontal cortex compared with those who did not (t=4.64; p<0.001). Patients
      in whom depression developed postoperatively also showed hypometabolism in the
      ipsilateral orbitofrontal region (t=5.10; p<0.001). CONCLUSIONS: Although this
      study is methodologically limited, and other explanations merit consideration,
      orbitofrontal cortex dysfunction, already implicated in the pathophysiology of
      nonepileptic depression, may also be relevant to the depression of TLE and
      temporal lobectomy.

PMID- 17201713
TI  - A prospective study of postictal psychoses with emphasis on the periictal type.
AB  - PURPOSE: To assess prospectively episodes of postictal psychosis. METHODS: We
      followed 108 consecutive patients with temporal lobe epilepsy, who were divided
      into three groups: those without psychotic episodes (n=87, N group), those with
      interictal psychosis (n=13, IIP group), and those with postictal psychosis (n=8,
      PIP group). The first episode of postictal psychosis, which was defined as a
      psychotic episode that occurred within 1 week after the end or within 3 days
      before the beginning of seizure clusters, was assessed with the Brief Psychiatric
      Rating Scale (BPRS) and Social Dysfunction and Aggression Scale (SDAS) during the
      observation period. RESULTS: The duration of illness was significantly different
      between the N and PIP groups (p=0.004) and between the N and IIP groups
      (p=0.039). The average initial BPRS score (obtained 3.0 days after the end of the
      seizure cluster) was 19.7, and then decreased to 5.8 after 1 week, and finally
      normalized at 1.5 after 1 month. A statistically significant decrease in BPRS
      scores was found between the initial assessment and those obtained after 1 week
      (p=0.011). Those who had psychotic episodes without a lucid interval tended to
      have episodes more often than monthly, and experienced additional seizure
      recurrence even during the psychotic episodes. Two patients exhibited a frank
      manic phase, and three patients showed excessively aggressive behavior, as
      determined by the SDAS. CONCLUSIONS: Postictal psychosis should be subdivided
      into the nuclear type, with an established clinical picture as an indirect
      aftereffect of seizure activity, and the atypical periictal type, which is a
      direct manifestation of limbic discharge.

PMID- 17201714
TI  - Sexual dysfunctions and blood hormonal profile in men with focal epilepsy.
AB  - PURPOSE: To evaluate the incidence of sexual dysfunction in men with focal
      epilepsy and to establish their hormonal profiles. METHODS: We prospectively
      analyzed sexual functions and hormone blood levels in 40 male patients (age
      ranged from 18 to 44 years, with an average age of 27.6+/-5.6 years) with
      refractory focal epilepsy. We used the Czech version of the structured
      questionnaire entitled International Inventory of Erectile Function (IIEF) to
      assess the patients' sexual functions. The subscales of this questionnaire
      separately evaluate erectile function (IIEF I), orgasmic function (IIEF II),
      sexual desire (IIEF III), intercourse satisfaction (IIEF IV), and overall
      satisfaction with sex life (IIEF V). In all of the patients, the following blood
      tests were performed: quantitative assessment of blood levels of prolactin (PRL),
      total testosterone (total-T), free androgen index (FAI), sexual hormone-binding
      globulin (SHBG), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS),
      progesterone (PRG), follicle-stimulating hormone (FSH), and luteinizing hormone
      (LH). All these quantitative laboratory data were correlated with other clinical
      variables and with the results of the IIEF. chi2 and Wilcoxon tests were used for
      the statistical analysis. A p-value<0.05 was considered to be statistically
      significant. RESULTS: At least one of the types of sexual dysfunction, as defined
      by IIEF (IIEF I, II, and III), was found in 22 (55%) of the 40 patients (55%).
      Erectile dysfunction (IIEF I) was found in six (15%) of 40 patients, orgasmic
      dysfunction (IIEF II) in six (15%) of 40 patients, and loss of sexual desire
      (IIEF III) in 16 (40%) of 40 patients. According to other subscales of IIEF, 22
      (55%) of 40 patients were not satisfied with sexual intercourse (IIEF IV), and 20
      (50%) of 40 patients were not satisfied with their sex livee (IIEF V). None of
      the subscales of IIEF was significantly correlated with the age of the patients
      or with the duration of epilepsy. In patients with at least one of the sexual
      dysfunctions (IIEF I, II, and III), we found a statistically significant increase
      of FSH and SHBG, and a decrease of DHEAS and FAI in comparison with those in the
      patients with normal sexual functions. In patients with erectile dysfunction, we
      found the same changes and a significant increase of E2. In patients with
      orgasmic dysfunction, we found a statistically significant decrease of DHEAS. In
      patients with dysfunction of sexual desire, we noticed a significant increase of
      SHBG and a decrease of DHEAS and FAI. All patients with orgasmic dysfunction were
      being treated with carbamazepine (CBZ) in monotherapy or combination therapy. In
      patients with at least one type of sexual dysfunction (IIEF I, II, and III), we
      found a higher proportion of valproate treatment in monotherapy or combination
      therapy in comparison with CBZ. CONCLUSIONS: Our study showed a relatively high
      incidence of sexual dysfunction and dissatisfaction with sexual intercourse and
      sex life, as defined by the IIEF I-V questionnaire, in men with refractory focal
      epilepsy. The most frequent dysfunction in these patients is the impairment of
      sexual desire. However, our study indicates some specific hormonal changes
      related to various types of sexual dysfunction that are not related to
      antiepileptic drug treatment.

PMID- 17201715
TI  - Mesial temporal lobe epilepsy impairs advanced social cognition.
AB  - PURPOSE: Although memory, language, and executive functions have been extensively
      studied in patients with mesial temporal lobe epilepsy (MTLE), investigations
      into advanced social cognitive abilities have been neglected. In the present
      study, we investigated the ability to detect social faux pas and studied possible
      mediating clinical and demographic variables in patients with MTLE compared with
      patients with an epilepsy not originating within the MTLE and healthy controls.
      METHODS: The 27 MTLE patients (16 were investigated pre- and 11 postoperatively),
      27 patients with an extramesiotemporal epilepsy (except frontal lobe epilepsy),
      and 12 healthy controls performed a shortened version of the faux-pas test.
      Additionally, we used standardized tests to measure intelligence. Only patients
      with intact reading-comprehension abilities were included in the study. RESULTS:
      MTLE patients, both pre- and postoperative, performed the faux-pas test
      significantly worse than patients with extramesiotemporal lobe epilepsy and
      healthy controls. The latter two groups showed comparable performance. No
      statistical association was found between the MTLE patients' deficit in
      recognizing a faux pas and the variables IQ, age, age at seizure onset, and
      duration of epilepsy. CONCLUSIONS: We report for the first time that patients
      with MTLE are specifically impaired in recognizing faux pas, suggesting that MTLE
      as such is a specific etiology of deficits in higher-order social cognition.

PMID- 17201716
TI  - Cerebral malaria and sequelar epilepsy: first matched case-control study in
      Gabon.
AB  - PURPOSE: Cerebral malaria (CM) is suspected to be a potential cause of epilepsy
      in tropical areas. The purpose of this article was to evaluate the relationship
      between CM and epilepsy in Gabon. METHODS: A matched case-control study was
      carried out on a sample of subjects aged six months to 25 years and hospitalized
      between 1990 and 2004 in three hospitals in Libreville, Gabon. Cases were defined
      as patients suffering from epilepsy and confirmed by a neurologist. Controls were
      defined as patients without epilepsy. The exposure of interest was CM according
      to WHO criteria. RESULTS: In total, 296 cases and 296 controls were included. Of
      these, 36 (26 cases and 10 controls) had a CM history. The adjusted odds ratio
      (aOR) to develop epilepsy after CM was 3.9 [95% CI: 1.7-8.9], p<0.001. Additional
      risk factors were identified: family history of epilepsy: aOR=6.0 [95% CI: 2.6
      14.1], p<0.0001, and febrile convulsions: aOR=9.2 [95% CI 4.0-21.1], p<0.0001.
      CONCLUSIONS: This first case-control study on that issue suggests that epilepsy
      related CM is an underrecognized problem. It emphasizes the need for further
      studies to better evaluate the role of convulsions during CM.

PMID- 17201717
TI  - A survey of public awareness, understanding, and attitudes toward epilepsy in
      Greece.
AB  - PURPOSE: To assess familiarity, understanding, and attitude toward epilepsy in
      Greece and identification of negative predictive factors. METHODS: A 19-item
      questionnaire was administered to 750 adults. The magnitude of social stigma
      toward epileptic people with epilepsy was measured with a quantitative scale of
      social rejection. Statistical analysis with chi-square and multiple regression
      analysis were used to identify factors associated with negative attitudes.
      RESULTS: Of our respondents 38.8% knew someone with epilepsy and 50.8% had
      witnessed a seizure. Nineteen percent believed that epilepsy is a type of mental
      retardation, 15% believed it is a type of insanity, 91.8% considered epilepsy as
      a brain disorder while 5.2% considered it as a supernatural phenomenon. Seventy
      seven percent considered epilepsy as a curable disease while 57.5% believed that
      the risk of inheriting it is very high. Regarding marriage to a patient with
      epilepsy 45.4% rejected it while regarding his employment 37.7% were positive,
      47.8% were skeptical while 12.8% were against it. The Greek public's rejection
      tendency toward epileptic people was generally low. Negative predictive factors
      were older age, low educational level, unfamiliarity with epilepsy, and erroneous
      beliefs about epilepsy. CONCLUSIONS: The Greek public is familiar with epilepsy
      but has a suboptimal level of appropriate understanding of essential aspects of
      the disease. The overall public's level of rejection toward people with epilepsy
      is low but certain groups of people are highly rejective. Information campaigns
      targeting specific population subgroups are necessary in Greece in order to
      improve the public's understanding of epilepsy and tolerance toward people with
      epilepsy.

PMID- 17201718
TI  - Direct and indirect costs of refractory epilepsy in a tertiary epilepsy center in
      Germany.
AB  - PURPOSE: There are only few studies on the costs of epilepsy in Germany.
      Therefore, we performed a pilot study to estimate the direct and indirect costs
      of refractory epilepsy in a German epilepsy center. METHODS: A "prevalence
      based," cross-sectional convenience sample of adults with active epilepsy
      attending the outpatient clinic of our tertiary epilepsy center was evaluated.
      Seizure-free patients and patients presenting with their first seizure were
      excluded. Direct and indirect costs were prospectively recorded over a three
      month period using questionnaires and a patient diary. Cost driving factors were
      identified. RESULTS: One hundred one patients were included (40.7+/-15.2 years;
      disease duration: 18.1+/-15.3 years; 6 patients had focal epilepsy with simple
      partial seizures only, 28 with complex partial seizures, 43 with secondarily
      generalized tonic-clonic seizures; 20 had idiopathic generalized epilepsy with
      generalized tonic-clonic seizures). The total costs of epilepsy per patient were
      in average euro 2610+/-4200 over the three-month period. Direct cost contributed
      39% to the total costs. Costs of anticonvulsant medication were the main
      contributor to the direct costs while indirect costs were caused mainly by losses
      due to early retirement. Cost driving factors included higher seizure frequency,
      longer disease duration, ictal falls, and situationally inappropriate complex
      behavior during or after the seizure. CONCLUSIONS: Indirect costs were higher
      than direct costs in adult patients with active epilepsy attending a German
      epilepsy center. Medication contributed the most to the direct costs and early
      retirement was the main factor for the indirect costs. The costs of poorly
      controlled epilepsy in this German study were above average of the European costs
      of epilepsy.

PMID- 17201719
TI  - Evaluation of acceptance and commitment therapy for drug refractory epilepsy: a
      randomized controlled trial in South Africa--a pilot study.
AB  - PURPOSE: Psychological interventions in the treatment of epilepsy have been
      developed and evaluated for many years but the amount of research has hardly made
      an impact on how epilepsy is treated. The purpose of this study was to develop
      and evaluate a psychological treatment program consisting of acceptance and
      commitment therapy (ACT) together with some behavioral seizure control technology
      shown to be successful in earlier research. METHODS: The method consisted of a
      randomized controlled trial group design with repeated measures (n=27). All
      participants had an EEG verified epilepsy diagnosis with drug refractory
      seizures. Participants were randomized into one of two conditions, ACT or
      supportive therapy (ST). Therapeutic effects were measured by examining changes
      in quality of life (SWLS and WHOQOL) and seizure index (frequency x duration).
      Both treatment conditions consisted of only nine hours of professional therapy
      distributed in two individual and two group sessions during a four-week period.
      RESULTS: The results showed significant effects over all of the dependent
      variables for the ACT group as compared to the ST group at six- and twelve-month
      follow-ups. CONCLUSIONS: The results from this study suggest that a short-term
      psychotherapy program combined with anticonvulsant drugs may help to prevent the
      long-term disability that occurs from drug refractory seizures.

PMID- 17201720
TI  - Micturition and emotion-induced reflex epilepsy: case report and review of the
      literature.

PMID- 17201721
TI  - The frequency of reversible parkinsonism and cognitive decline associated with
      valproate treatment: a study of 364 patients with different types of epilepsy.
AB  - PURPOSE: We report the frequency of parkinsonism and cognitive decline (P/CD) in
      patients treated with valproate (VPA) after 1 year of treatment and at least 1
      year of follow-up. METHODS: Three hundred sixty-four patients with various
      epileptic syndromes and seizure types were treated with VPA mono- or polytherapy
      for more than 1 year. RESULTS: We found five cases of P/CD (1.37%; 95% CI, 0.18
      2.56%). Among 140 patients with different adverse effects (AEs) of VPA, P/CD were
      among the rarest in frequency but significant in terms of drug discontinuation
      (five of 17). CONCLUSIONS: Early identification of this type of AE and
      discontinuation of the drug led to complete recovery in affected patients.

PMID- 17201722
TI  - Use of levetiracetam in hospitalized patients.
AB  - PURPOSE: The objective of the study was to analyze the short-term efficacy and
      safety of levetiracetam (LEV) to treat repetitive seizures in hospitalized
      patients. METHODS: During admission to a tertiary hospital, we retrospectively
      identified patients with repetitive seizures who were treated for the first time
      with LEV during a hospital stay. LEV was considered effective if seizure
      cessation or >75% seizure reduction occurred in the 24 h after starting LEV
      (compared with the previous 48 h), requiring no further antiepileptic drug (AED)
      treatment. RESULTS: Thirty patients (12 men, 18 women) were included. Mean age
      was 59.7 years. Most frequent seizure type was focal motor in 12 (40%) of 30
      patients. Most frequent etiology was stroke: nine (30%) of 30 patients. Relevant
      medical conditions included atrial fibrillation (three) and hepatic disease
      (three). Concomitant medications included oral anticoagulants (seven),
      corticosteroids (two), and chemotherapy (two). Four patients received LEV as the
      only AED. Six patients with focal SE and 20 (66.6%) patients with clusters of
      seizures but not in SE received LEV as add-on treatment after lack of response to
      first-line AEDs. Mean LEV dose during first day was 1,119 mg. Mean daily
      maintenance dose was 1,724 mg. LEV was effective in 24 (80%) patients, all four
      patients who received it as the only AED, four of six patients with focal SE, and
      16 of 20 patients with clusters of seizures. Three (10%) elderly patients with
      seizures secondary to stroke and chronic obstructive pulmonary disease (COPD)
      reported moderate/severe somnolence and dizziness, leading to treatment
      discontinuation in one. On discharge, 20 (66.7%) patients continued on LEV, nine
      (30%) as the only AED. CONCLUSIONS: LEV is effective and safe to treat repetitive
      seizures in hospitalized patients, including patients in focal SE.

PMID- 17201723
TI  - Rhythmic ictal nonclonic hand (RINCH) motions: a distinct contralateral sign in
      temporal lobe epilepsy.
AB  - PURPOSE: To describe a new ictal sign in temporal lobe seizures-rhythmic ictal
      nonclonic hand (RINCH) motions and to determine its lateralizing significance and
      other ictal manifestations associated with it. METHODS: We identified 15 patients
      with temporal lobe epilepsy who demonstrated RINCH motions and reviewed video-EEG
      recordings of all their seizures. We analyzed the epilepsy characteristics and
      all clinical features of recorded seizures, with particular attention to RINCH
      motions. RESULTS: RINCH motions were unilateral, rhythmic, nonclonic, nontremor
      hand motions. RINCH motions were usually followed by posturing, sometimes with
      some overlap. They involved the hand contralateral to the temporal lobe of
      seizure onset in 14 of 15 patients. CONCLUSIONS: RINCH motions are a distinct
      ictal sign that could be considered a specific type of automatism. They appear to
      be a lateralizing contralateral sign and are associated with dystonic posturing
      in temporal lobe epilepsy.

PMID- 17201724
TI  - Orgasm-induced seizures: a study of six patients.
AB  - PURPOSE: Reflex seizures are known as the epileptic seizures triggered by some
      specific stimuli in sensitive patients. They are often classified according to
      the stimuli that trigger them rather than by the type of the seizure. Epileptic
      seizures induced by sexual orgasm are very rare in the literature. METHODS: We
      report six patients with different epileptic syndromes who experienced seizures
      after sexual intercourse and orgasm. RESULTS: All patients are women whose
      epileptogenic focus was in the right temporal in four and left frontal in one
      patient. One patient had pure generalized reflex epilepsy. CONCLUSIONS: Seizures
      induced by orgasm are very rare, with female and right hemisphere dominance
      requiring complex mechanisms to occur.

PMID- 17201725
TI  - Nonlesional frontal lobe epilepsy (FLE) of childhood: clinical presentation,
      response to treatment and comorbidity.
AB  - RATIONALE: Few studies have looked at long-term epileptic and cognitive outcome
      of frontal lobe epilepsy (FLE) in children. Most are limited by inclusion of
      lesional and nonlesional patients. GOAL: To define the epileptic and functional
      outcome of children with nonlesional FLE. METHODS: We reviewed medical records
      and neuropsychological evaluations of patients with nonlesional FLE diagnosed
      between 1994 and 2004. We included children with either focal or regional frontal
      EEG and/or functional imaging abnormalities. We reviewed their charts for seizure
      and neuropsychological outcome. RESULTS: We included 21 children. Twelve (57.1%)
      presented with daily seizures. Seizures were nocturnal in 8 of 21, secondarily
      generalized in 6 of 21, adversive in 5 of 21, and focal motor in 6 of 21.
      Although, initial seizure control was poor in 14 of 21, long-term control was
      achieved in 10 of 21 after 14.6+/-22.3 months. Early development was normal in 12
      of 21 but at later formal neuropsychological evaluation only 3 of 12 still had a
      normal profile. The majority of children had learning difficulties requiring
      special education prior to seizure onset (6 of 10). A clearly defined regression
      after seizure onset was observed in three children. The majority exhibited
      attention deficit and hyperactivity or impulsivity (14 of 21), behavioral
      problems (8 of 21), and cognitive impairments (10 of 21). Early seizure control
      was associated with a better cognitive outcome. CONCLUSION: Nonlesional FLE is
      associated with poor seizure and behavioral outcomes. Whether this is secondary
      to MRI-silent developmental lesions or to the progressive repercussion of
      seizures on frontal lobe functions remains uncertain. A prospective study with
      early neuropsychological assessment could help confirm the latter.

PMID- 17201726
TI  - The risk of lower mental outcome in infantile spasms increases after three weeks
      of hypsarrhythmia duration.
AB  - To assess the correlation between hypsarrhythmia duration and mental outcome in
      infantile spasms (IS) the medical records of 48 infants with IS were reviewed
      retrospectively and psychological assessments undertaken at follow-up at the age
      of 3 to 13 years. We found 18 (38%) cryptogenic IS cases with typical
      hypsarrhythmia and 30 symptomatic with modified hypsarrhythmia-further classified
      into 15 cases as multifocal, 10 as pseudoperiodic and 5 as unilateral
      hypsarrhythmia. A short treatment lag (one to two weeks) occurred in 25, three to
      four weeks in 10 cases. Spasms ceased within one month after treatment in 23
      infants. At follow-up 15 children had normal mental outcome (borderline
      included). A correlation between hypsarrhythmia duration longer than three weeks
      and lower mental outcome was found using the logistic regression model. The
      duration of hypsarrhythmia represents a sensitive prognostic parameter in IS; the
      risk of mental retardation increases after three weeks of hypsarrhythmia.

PMID- 17201727
TI  - Reduced absorption of lipophilic anti-epileptic medications when used
      concomitantly with the anti-obesity drug orlistat.

PMID- 17201728
TI  - Sleep and metabolic control: waking to a problem?
AB  - 1. The aim of the present review is to outline: (i) the association between sleep
      and metabolism; (ii) how sleep duration influences the development of disease;
      and (iii) how sex differences, ageing and obesity may potentially influence the
      relationship between sleep, metabolic control and subsequent disease. 2. Sleep is
      associated with a number of endocrine changes, including a change in insulin
      action in healthy young individuals. Sleep duration shows a prospective U-shaped
      relationship with all-cause mortality, cardiovascular disease and Type 2
      diabetes. 3. Chronic sleep restriction is becoming more common. Experimental
      sleep restriction impedes daytime glucose control and increases appetite. 4. The
      sex hormones oestrogen and testosterone influence sleep duration and quality and
      may account for sex differences in the prevalence of sleep-related disorders. 5.
      Ageing is associated with a decreased sleep duration, decreased muscle mass and
      impaired insulin action. 6. Obesity impairs insulin action and is associated with
      the incidence and severity of obstructive sleep apnoea. 7. Sleep plays an
      integral role in metabolic control. Consequently, insufficient sleep may
      represent a modifiable risk factor for the development of Type 2 diabetes. The
      challenge ahead is to identify how sex differences, ageing and obesity could
      potentially influence the relationship between sleep and metabolism.

PMID- 17201729
TI  - Effect of BAY 41-2272 in the pulmonary hypertension induced by heparin-protamine
      complex in anaesthetized dogs.
AB  - 1. BAY 41-2272 is a potent activator of the nitric oxide-independent site of
      soluble guanylate cyclase and has been recently introduced as a new therapeutic
      agent to treat chronic pulmonary hypertension (PH) in neonatal sheep. Because the
      in vivo heparin-protamine interaction may lead to severe PH, the aim of the
      present study was to evaluate the effects of BAY 41-2272 in the PH induced by
      heparin-protamine interaction in anaesthetized dogs. 2. Sixteen male dogs (10
      mongrel dogs and six Beagles) were anaesthetized and instrumented for acquisition
      of mean arterial blood pressure (MABP), mean pulmonary arterial pressure (MPAP),
      heart rate (HR), pulmonary capillary wedge pressure (PCWP), cardiac index (CI)
      and indices of systemic and pulmonary vascular resistance (ISVR and IPVR,
      respectively). Plasma cGMP levels and S(p)o(2) were evaluated. 3. Intravenous
      administration of heparin (500 IU/kg) followed 3 min later by protamine (10
      mg/kg) caused marked PH, as evaluated by the increase in MPAP, PCWP and IPVR.
      This was accompanied by a significant fall in MABP and a transient increase in
      HR. Infusion of BAY 41-2272 (10 microg/kg per h, starting 10 min before heparin
      administration) augmented plasma cGMP levels and slightly and significantly
      increased HR and CI, without affecting the other cardiovascular parameters. The
      elevation in IPVR, MPAP and PCWP triggered by the heparin-protamine interaction
      was significantly reduced in animals exposed to BAY 41-2272. 4. In vehicle
      treated dogs, the S(p)o(2) values decreased significantly at the peak of the PH
      and this was significantly attenuated by treatment with BAY 41-2272. In addition,
      BAY 41-2272 (10 micromol/L) had no effect on the activated partial thromboplastin
      time of citrated plasma after the addition of heparin-protamine. 5. In
      conclusion, BAY 41-2272 was effective in reducing canine PH induced in vivo by
      the heparin-protamine interaction, thus indicating its potential in the treatment
      of this type of disorder.

PMID- 17201730
TI  - Ca2+-dependent differential development of carbachol-induced desensitization to
      receptor agonists and high K+ in guinea-pig taenia caeci.
AB  - 1. Carbachol (CCh)-induced desensitization to CCh was interrupted by a transient
      resensitization during its early stage, with concomitant changes at the
      muscarinic receptor/G-protein level in smooth muscle of guinea-pig taenia caeci.
      To assess whether such a peculiar desensitizing process may heterologously
      regulate smooth muscle contraction, we examined the developmental processes of
      CCh-induced desensitization to histamine and high K(+) and compared it with that
      to CCh. 2. Under Ca(2+)-containing physiological conditions, treatment with 10(
      4) mol/L CCh for 30 min induced heterologous desensitization to histamine and
      high K(+). The development of desensitization to histamine was interrupted by a
      transient resensitization at 1 min in a manner similar to that to CCh. In
      contrast, CCh-induced desensitization to high K(+) reached a peak at 1 min and
      was followed by a gradual resensitization up to a partial restoration at 30 min.
      3. Under Ca(2+)-free conditions containing 0.2 mmol/L EGTA, treatment with 10(-4)
      mol/L CCh for 30 min failed to induce heterologous desensitization to either
      histamine or high K(+), whereas the CCh treatment developed homologous
      desensitization to CCh in a simple time-dependent manner without a
      resensitization phase. 4. These results suggest that cellular responsiveness to
      receptor agonists and non-receptor-mediated depolarizing stimulation is
      differentially regulated by Ca(2+)-dependent heterologous desensitization in
      smooth muscle.

PMID- 17201731
TI  - The specific free radical scavenger edaravone suppresses bleomycin-induced acute
      pulmonary injury in rabbits.
AB  - 1. Intratracheal instillation of bleomycin induces a condition in rabbits that
      serves as a useful model of human pulmonary fibrosis. Bleomycin-induced
      production of reactive oxygen species leads to acute lung inflammation and
      induction of apoptosis, which is followed by pulmonary fibrosis at a later
      chronic stage. In the present study, we tested whether edaravone, a free radical
      scavenger, would suppress bleomycin-induced acute pulmonary inflammation. 2.
      Rabbits were divided into three groups (n = 10 in each): (i) a bleomycin-treated
      group, which received intratracheal instillation of 2 mg/kg bleomycin; (ii) a
      bleomycin + edaravone group, which received a 10 day regimen of daily intravenous
      injections of edaravone (3 mg/kg per day) beginning 3 days before bleomycin
      instillation; and (iii) a saline control group. Rabbits were killed for analysis
      7 days after bleomycin administration. 3. In lung tissues from the bleomycin
      treated group, marked infiltration of inflammatory cells, consisting mainly of
      lymphocytes, neutrophils and eosinophils, was observed. In addition,
      significantly increased numbers of TUNEL-positive (apoptotic) and transforming
      growth factor-beta-positive cells were seen. All these effects were significantly
      attenuated by treatment with edaravone. 4. The findings of the present study
      suggest that edaravone may be useful in the prevention of acute lung injury
      resulting from the production of reactive oxygen species.

PMID- 17201732
TI  - Effects of fenofibrate and xuezhikang on high-fat diet-induced non-alcoholic
      fatty liver disease.
AB  - 1. Fenofibrate and xuezhikang are two types of drugs widely used in the treatment
      of dyslipidaemia in China. The main purpose of present study was to test the
      efficacies and explore the potential mechanisms of action of the two lipid
      lowering agents on high-fat diet-induced non-alcoholic fatty liver disease
      (NAFLD). 2. Rats were randomly divided into four groups, with eight rats per
      group. One group was given normal diet, whereas the other three groups were fed a
      high-fat diet. Forty-two days later, two of the high-fat diet-fed groups were
      administered fenofibrate (100 mg/kg, p.o.) and xuezhikang (300 mg/kg, p.o.) for
      another 42 consecutive days. The other two groups were administered placebo
      (saline) by gavage. 3. Typical pathological symptoms of NAFLD occurred in the
      high-fat diet groups. Fenofibrate and xuezhikang treatment markedly improved
      NAFLD, ameliorating dyslipidaemia and fat accumulation in the liver, improving
      insulin resistance and ameliorating oxidative stress. Hepatic steatosis, necro
      inflammation and collagen deposition were lessened in the drug-treated groups.
      However, both xuezhikang and fenofibrate failed to reverse hepatomegaly and
      fenofibrate even aggravated it. Xuezhikang reversed aminotransferase
      abnormalities, but fenofibrate had less of an effect. 4. The common therapeutic
      mechanism of action of fenofibate and xuezhikang likely involves inhibition of
      the hepatic expression of tumour necrosis factor-alpha. Fenofibrate upregulated
      mRNA levels of peroxisome proliferator-activated receptor (PPAR) alpha in the
      liver, whereas xuezhikang had no effect on the hepatic expression of PPARalpha
      and this may explain, in part, their different effects on the NAFLD rats. 5. The
      results suggest that fenofibrate and xuezhikang may have potential clinical
      application in the treatment of NAFLD. However, the side-effects of fenofibrate
      and the underlying constituents of xuezhikang need to be determined and
      investigated further.

PMID- 17201733
TI  - Cyclo-oxygenase-2 inhibition attenuates the progression of nephropathy in
      uninephrectomized diabetic rats.
AB  - 1. Cyclo-oxygenase (COX)-2 is involved in constitutive production of prostanoids
      in the kidney and plays a role in the control of renal function and morphology.
      Renal cortical COX-2 expression and function is increased in experimental models
      of diabetes (DM). However, pathophysiological roles of this phenomenon in the
      diabetic kidney have not been fully elucidated. To address this issue, we studied
      the nephroprotective potential of long-term (16 weeks) COX-2 inhibition in
      uninephrectomized streptozotocin-diabetic rats (D). 2. Diabetic rats received
      either a low or high dose of the selective COX-2 inhibitor MF-tricyclic (MF; 1 or
      5 mg/kg per day in chow). Another group of D rats received high-dose MF as late
      intervention starting at 8 weeks of DM (D-MFlate). The effects of treatments were
      compared with age-matched uninephrectomized diabetic and non-diabetic rats
      receiving drug-free chow (D-VE and C-VE, respectively). 3. No differences in
      blood pressure and metabolic control were observed between groups of D rats
      throughout the study. The D-VE group developed progressive albuminuria and
      glomerulosclerosis, associated with increased excretion of the thromboxane (TX)
      A(2) metabolite TxB(2). Treatment with MF attenuated albuminuria in diabetic rats
      with late intervention, but not in D rats treated with MF from the onset of DM.
      Moreover, D-MFlate rats demonstrated a significant reduction in the development
      of glomerulosclerosis. These effects coincided with prevention of diabetes
      induced rise in urinary TxB(2) excretion. 4. In conclusion, long-term COX-2
      inhibition is associated with modest nephroprotection in uninephrectomized
      diabetic rats when administered as late intervention. These effects are
      independent of metabolic control and blood pressure.

PMID- 17201734
TI  - Effect of alpha-adrenoceptor subtype-selective inverse agonists on non-pregnant
      and late-pregnant cervical resistance in vitro in the rat.
AB  - 1. The aim of the present study was to compare and elucidate the effects of
      alpha(1)-adrenoceptor (alpha(1)-AR) subtype-selective inverse agonists on non
      pregnant and late-pregnant rat cervical tone. 2. Cervical resistance was
      investigated in in vitro stretching tests in the absence or presence of alpha(1)
      AR subtype-selective inverse agonists (WB 4101, AH 11110A and BMY 7378; all at
      10(-6) mol/L), whereas the mRNA levels and density of the alpha(1)-AR subtypes
      and the G-protein-activating effects of the inverse agonists were determined by
      reverse transcription-polymerase chain reaction, western blot and [(35)S]
      GTPgammaS binding techniques, respectively. 3. The inverse agonists did not cause
      any change in resistance in non-pregnant and 18-day-pregnant samples. WB 4101
      increased cervical resistance from Day 20, whereas AH 11110A had no effect and
      BMY 7378 exhibited such an action only on Day 21. Phenylephrine (10(-4) mol/L)
      had no effect on cervical resistance on Day 22. The mRNA levels and density of
      all alpha(1)-AR subtypes were increased on Day 18, but no further changes were
      observed after that. The [(35)S]-GTPgammaS binding studies revealed increased G
      protein activation of alpha(1A)-AR and a moderate G-protein activation of
      alpha(1B)- and alpha(1D)-AR. The effect of WB 4101 to increase [(35)S]-GTPgammaS
      binding was blocked by pertussis toxin (50 ng/mL). Phenylephrine caused a slight
      and significant decrease in the amount of activated G-protein on Day 22. 4. The
      effects of inverse agonists on the alpha(1A)-AR can enhance cervical resistance
      in the late-pregnant rat in vitro. This action is mediated, at least in part, by
      a pertussis toxin-sensitive G(i)-protein. This effect of the alpha(1A)-AR inverse
      agonist WB 4101 may offer a new therapeutic target in the prevention of premature
      labour.

PMID- 17201735
TI  - Impaired effect of salt loading on nitric oxide-mediated relaxation in aortas
      from stroke-prone spontaneously hypertensive rats.
AB  - 1. The present study was designed to characterize the effects of salt on
      vasorelaxation via the nitric oxide (NO)/cGMP pathway in stroke-prone
      spontaneously hypertensive rats (SHRSP), which are highly salt sensitive. 2. Male
      8-week-old SHRSP were given 1% NaCl solution as drinking water for 4 weeks,
      whereas control animals were given water only. 3. In aortic rings from salt
      loaded SHRSP, relaxations in response to acetylcholine and sodium nitroprusside
      were significantly impaired compared with those in the control. In the presence
      of zaprinast, a cGMP-specific cyclic nucleotide phosphodiesterase (PDE)-5
      inhibitor, the cGMP levels induced by these drugs were significantly reduced by
      salt loading, but remained unchanged in the absence of zaprinast. The protein
      levels of endothelial NO synthase, soluble guanylate cyclase (sGC) and cGMP
      dependent protein kinase (PKG) remained unchanged with salt loading, but those of
      PDE-5 decreased significantly and those of phosphorylated PKG tended to decrease,
      although the change was not statistically significant. Salt loading significantly
      impaired the relaxation in response to 8-bromo-cGMP. 4. These results indicate
      that, in aortas from SHRSP, salt loading causes impairment of relaxation in
      response to NO, which may be due to a decrease in cGMP production by sGC and
      impairment of the relaxation pathway downstream of cGMP, which, in turn, probably
      causes a decrease in PKG activity. Reduced PDE-5 protein expression may act, in
      part, as a compensatory response to impairment of cGMP-mediated relaxation.

PMID- 17201736
TI  - Effects of landiolol on mechanical and metabolic changes in rat reperfused
      ischaemic hearts.
AB  - 1. The aim of the present study was to clarify the effects of landiolol, a short
      acting selective beta(1)-adrenoceptor blocking agent, on mechanical and metabolic
      changes in postischaemic perfused hearts. 2. Rat isolated hearts (n = 30) were
      randomly separated into non-ischaemic or ischaemic groups. The latter group was
      further divided into Krebs'-Henseleit solution (KHS)- and landiolol (30, 100 or
      300 micromol/L)-treated groups. Ischaemic hearts were subjected to 25 min global
      ischaemia and 20 min reperfusion under atrial pacing. Time-course changes in left
      ventricular (LV) end-diastolic pressure (LVEDP), LV developed pressure (LVDP),
      peak positive velocity of change of LV pressure (LVdP/dt(max)) and coronary flow
      were observed along with tissue contents of adenosine triphosphate (ATP),
      creatine phosphate, inorganic phosphate (Pi), malondialdehyde (MDA) and lactate
      dehydrogenase (LDH) release in coronary effluent. The effects of landiolol on rat
      isolated aortic preparations under KCl contraction were also investigated. 3.
      Ischaemia-reperfusion significantly impaired cardiodynamics, such as LVEDP, LVDP
      and LVdP/dt(max), decreased myocardial ATP content and increased Pi and LDH
      release. In the 30 micromol/L landiolol-treated group, cardiovascular parameters
      impaired by ischaemia-reperfusion and increased LDH release were further
      exacerbated and myocardial MDA content was significantly increased. In the 300
      micromol/L landiolol-treated group, cardiac contractile dysfunction was improved
      and myocardial MDA, ATP and Pi contents were preserved. All measurements in the
      100 micromol/L landiolol-treated group were similar to those in the ischaemic KHS
      group. Furthermore, significant relaxations of isolated aortic preparations were
      obtained with landiolol 30-1000 micromol/L, suggesting a possible calcium
      antagonism with landiolol. 4. In conclusion, landiolol, at low concentrations,
      aggravated myocardial ischaemia-reperfusion injuries, whereas at high
      concentrations it ameliorated them. The former effect may be mediated by the
      production of reactive oxygen species, whereas the latter may involve calcium
      antagonist activity.

PMID- 17201737
TI  - Endotoxin-induced acute lung injury is enhanced in rats with spontaneous
      hypertension.
AB  - 1. Acute lung injury (ALI), or acute respiratory distress syndrome, is a major
      cause of mortality in endotoxaemia. The present study tested whether the
      endotoxaemia-induced changes and associated ALI were enhanced in rats with
      established hypertension and to examine the possible mechanisms involved. 2.
      Fifty spontaneously hypertensive rats (SHR) and the same number of normotensive
      Wistar Kyoto (WKY) rats, aged 12-15 weeks, were used. The experiments were
      performed in conscious, unanaesthetized rats. Endotoxaemia was produced by
      intravenous lipopolysaccharide (LPS; 10 mg/kg). N(G)-Nitro-L-arginine methyl
      ester (L-NAME; 10 mg/kg, i.v.), L-N(6)-(1-iminoethyl)-lysine (L-Nil; 5 mg/kg,
      i.v.) and 3-morpholinosydnonimine (SIN-1; 5 mg/kg, i.v.) were given 5 min before
      LPS to observe the effects of nitric oxide synthase (NOS) inhibition and nitric
      oxide (NO) donation. 3. We monitored arterial pressure and heart rate and
      evaluated ALI by determining the lung weight/bodyweight ratio, lung weight gain,
      leakage of Evans blue dye, the protein concentration in bronchoalveolar lavage
      and histopathological examination. Plasma nitrate/nitrite, methyl guanidine, pro
      inflammatory cytokines, including tumour necrosis factor-alpha and interleukin
      1beta, and lung tissue cGMP were determined. Expression of mRNA for inducible and
      endothelial NOS was examined using reverse transcription-polymerase chain
      reaction. 4. Lipopolysaccharide caused systemic hypotension, ALI and increases in
      plasma nitrate/nitrite, methyl guanidine, pro-inflammatory cytokines and lung
      cGMP content. The LPS-induced changes were greater in SHR than in WKY rats.
      Pretreatment with L-NAME or L-Nil attenuated, whereas the NO donor SIN-1
      aggravated, the endotoxin-induced changes. 5. In conclusion, rats with genetic
      hypertension are more susceptible to endotoxaemia and this results in a greater
      extent of ALI compared with normotensive WKY rats.

PMID- 17201738
TI  - Effects of hyperbaric oxygen on glucose, lactate, glycerol and anti-oxidant
      enzymes in the skeletal muscle of rats during ischaemia and reperfusion.
AB  - 1. Hyperbaric (HBO(2)) and topical oxygen represent two accepted options to
      oxygenate tissues. The aim of the present study was to investigate the effect of
      HBO(2) on energy metabolism and anti-oxidant enzymes in a rat model of ischaemia
      reperfusion (IR) skeletal muscle injury. 2. In the first study, 16 rats were
      randomized to a HBO(2)-treated group (Group 1; n = 8) and an untreated group
      (Group 2; n = 8). Under general anaesthesia, right hind limb ischaemia was
      produced by application of a rubber-band tourniquet for 3 h. After 2 h ischaemia,
      Group 1 rats received HBO(2) during the last hour of ischaemia. The HBO(2)
      consisted of 100% oxygen delivered at 282.8 kPa absolute pressure. Group 2 rats
      were not treated. Following the ischaemic period, the tourniquet was released for
      1 h. A microdialysis probe was used to sample lactate, glucose and glycerol
      concentrations in the muscle extracellular tissue every 15 min throughout each
      experiment. 3. In the second study, 24 rats were randomized into four groups (n =
      6 each). The first two groups were subjected to the IR injury protocol outlined
      above and either treated (Group 1) or untreated (Group 2) with HBO(2). Group 3
      rats were anaesthetized, did not undergo IR injury, but underwent HBO(2)
      treatment. Group 4 rats were anaesthetized but did not undergo either IR injury
      or HBO(2) treatment. At end of each experiment, the biceps femoris muscle was
      removed and assayed for superoxide dismutase (SOD) and catalase (CAT) activity.
      Malondialdehyde (MDA) was measured to estimate the extent of membrane lipid
      peroxidation. 4. Three hours of skeletal muscle ischaemia resulted in a gradual
      decrease in the glucose concentration and a gradual increase in the lactate
      concentration within the extracellular fluid of the affected skeletal muscle
      tissue. Treatment with HBO(2) had no effect on the glucose concentration;
      however, HBO(2) significantly attenuated the ischaemia-induced increase in
      lactate and glycerol. In both groups, glucose concentration increased rapidly
      during reperfusion; glucose concentration returned to pre-ischaemic levels 15 min
      after reperfusion both with and without HBO(2). 5. Catalase activity and MDA
      increased significantly after 1 h of reperfusion. The HBO(2) attenuated the
      reperfusion-induced increase in CAT activity and MDA. 6. The results of the study
      suggest that HBO(2) may have some beneficial effect by decreasing lactate and
      glycerol levels and modulating anti-oxidant enzyme activity in postischaemic
      skeletal muscle in our rat model of tourniquet-induced IR skeletal muscle injury.

PMID- 17201739
TI  - Mouse strain-specific differences in cardiac metabolic enzyme activities observed
      in a model of isoproterenol-induced cardiac hypertrophy.
AB  - 1. Alterations in myocardial energy metabolism accompany pressure overload
      induced hypertrophy. We previously described a novel model of catecholamine
      induced hypertrophy in which A/J mice exhibit more robust cardiac hypertrophy
      than B6 mice. Accordingly, we assessed the influence of mouse strain on the
      activities of key myocardial metabolic enzymes and whether there are strain
      related metabolic adaptations to short-term, high-dose isoproterenol (ISO)
      administration. 2. Thirty-nine male mice (19 A/J mice, 20 B6 mice), aged 12-15
      weeks, were randomly assigned to receive either ISO (100 mg/kg, s.c.) or vehicle
      (sterile water) daily for 5 days. On Day 6, all hearts were excised, weighed,
      freeze clamped and assayed for pyruvate dehydrogenase (PDH), medium chain acyl
      CoA dehydrogenase, carnitine palmitoyl transferase I and citrate synthase
      activities. Plasma fatty acids (FA) were also measured. 3. The ISO-treated A/J
      mice demonstrated greater percentage increases in gravimetric heart
      weight/bodyweight ratio than ISO-treated B6 mice (24 vs 3%, respectively; P <
      0.001). All enzyme activities were significantly greater in vehicle-treated B6
      mice than in A/J mice, illustrating a greater capacity for aerobic metabolism in
      B6 mice. Administration of ISO reduced PDHa (active form) activity in B6 mice by
      47% (P < 0.001), with no significant change seen in A/J mice. Free FA levels were
      not significantly different between groups; thus, the differences in PDHa were
      not due to changes in FA. 4. The basal activity of myocardial metabolic enzymes
      is greater in B6 mice than in A/J mice and ISO alters myocardial PDH activity in
      a mouse strain-dependent manner. Compared with A/J mice, B6 mice demonstrate less
      ISO-induced cardiac hypertrophy, but greater activity of key enzymes regulating
      FA and carbohydrate oxidation, which may protect against the development of
      hypertrophy. The metabolic adaptations associated with ISO-induced hypertrophy
      differ from those reported with pressure overload hypertrophy.

PMID- 17201740
TI  - Cardiac-specific overexpression of catalase prolongs lifespan and attenuates
      ageing-induced cardiomyocyte contractile dysfunction and protein damage.
AB  - 1. Oxidative stress plays a role in senescence-associated organ deterioration.
      This is supported by the beneficial effects of anti-oxidants against ageing
      related organ damage, although their role in cardiac ageing has not been
      elucidated. 2. The aim of the present study was to examine the impact of cardiac
      specific overexpression of catalase, an enzyme for H(2)O(2) detoxification, on
      cardiac contractile function and protein damage in young (3-4 months) and old (26
      28 months) male mice. Lifespan was analysed using the Kaplan-Meier survival
      curve. Cardiomyocyte contractile indices at various stimulus frequencies (0.1-5.0
      Hz) were analysed, including peak shortening (PS), time to 90% PS, time to 90%
      relengthening (TR(90)) and maximal velocity of shortening/relengthening (+/
      dL/dt). Protein damage was assessed using protein carbonyl formation. Catalase
      transgenic mice showed longer lifespan than wild-type FVB mice. The catalase
      transgene itself did not alter bodyweight or organ weight, or myocyte function.
      Ageing depressed +/-dL/dt and prolonged TR(90), but had no effect on other
      indices in FVB mice. Increased frequency triggered decreases in PS amplitude were
      exaggerated in aged FVB myocytes. Interestingly, ageing-induced mechanical
      defects were significantly attenuated in myocytes from catalase mice. Protein
      carbonyl formation was elevated in aged FVB compared with young FVB mice, which
      was significantly diminished in catalase mice. The proteomes of the myocardium of
      young or old FVB and catalase mice were compared using two-dimensional gel
      electrophoresis and mass spectrometry. Six proteins with differential expression
      between young and old FVB groups were tentatively identified, some of which were
      reversed by catalase. 3. In summary, the present data suggest that catalase
      protects cardiomyocytes from ageing-induced contractile defects and protein
      damage.

PMID- 17201741
TI  - Pulmonary vascular reactivity of spontaneously hypertensive rats is exacerbated
      in response to the central administration of exogenous nitric oxide.
AB  - 1. Centrally, nitric oxide (NO) is a sympathoinhibitory substance. Spontaneously
      hypertensive rats (SHR) have an impaired central nitroxidergic system and,
      consequently, NO-mediated decrease in sympathetic activity is exacerbated in SHR
      compared with Wistar-Kyoto (WKY) rats. We have demonstrated previously that acute
      hypoxic pulmonary vasoconstriction (HPV) is enhanced by central NO
      administration. Therefore, in the present study, we hypothesized that
      accentuation of the HPV by NO would be exacerbated in SHR compared with WKY rats.
      2. Mean pulmonary arterial pressure, systemic mean arterial blood pressure,
      cardiac output and heart rate were measured in pentobarbitone-anaesthetized,
      artificially ventilated, male SHR and WKY rats. The brief, transient response to
      a bolus intracerebroventricular (i.c.v.) dose of N(G)-nitro-L-arginine methyl
      ester (L-NAME; 150 microg in 10 microL) was recorded in all rats. Upon recovery,
      rats were exposed to acute hypoxia (10% O(2) for 4 min) before and after the
      i.c.v. administration of the NO donor 3-[4-morpholinyl]-sydnonimine-hydrochloride
      (SIN-1; 100 microg in 10 microL). 3. In WKY rats, central inhibition of NO
      synthesis by L-NAME caused a mild increase in tonic pulmonary vascular tone and
      induced a large systemic pressor response. These responses were not observed in
      SHR. In contrast, SIN-1 failed to alter tonic pulmonary vascular tone, although
      it enhanced the HPV in WKY rats and, significantly more so, in SHR. 4. These
      results confirm that accentuation of the HPV by NO is exacerbated in SHR compared
      with WKY rats. The mechanism(s) by which the HPV is accentuated by central NO
      remains to be fully elucidated, but is likely to be associated with the
      sympathoinhibitory effects of NO and, if so, supports the idea that the
      nitroxidergic system of the SHR is impaired. Further electrophysiological studies
      are essential to confirm these assumptions.

PMID- 17201742
TI  - Endogenous nitric oxide attenuates beta-adrenoceptor-mediated relaxation in rat
      aorta.
AB  - 1. Divergent evidence suggests that the intracellular signalling pathways for
      beta-adrenoceptor-mediated vascular relaxation involves either cAMP/protein
      kinase (PK) A or endothelial nitric oxide (NO) release and subsequent activation
      of cGMP/PKG. The present study identifies the relative roles of NO and cAMP, as
      well as dependence on the endothelium for beta-adrenoceptor-mediated relaxation
      of rat isolated aortas. 2. Cumulative concentration-response curves to
      isoprenaline (0.01-3 micromol/L) in phenylephrine (0.1 micromol/L)-preconstricted
      endothelium-intact and -denuded aortas were constructed. Isoprenaline-mediated
      relaxation was partially reduced by endothelium removal and the presence of the
      NO synthase inhibitor N(G)-monomethyl-L-arginine (0.1 mmol/L), but not by the
      cAMP antagonist (Rp)-cyclic adenosine-3',5'-monophosphorothioate (Rp-cAMPS; 0.5
      mmol/L). 3. In contrast, in endothelium-denuded aortas, the isoprenaline-mediated
      relaxation was inhibited by Rp-cAMPS and this inhibition was lost in the presence
      of the NO donor sodium nitroprusside (1 nmol/L). This effect was not due to
      phosphodiesterase (PDE) activity because the non-selective PDE inhibitor 3
      isobutyl-1-methylxanthine (1 micromol/L) failed to affect the isoprenaline
      vasorelaxant response. 4. The K(+) channel blocker tetraethylammonium (TEA; 1
      mmol/L) attenuated isoprenaline-induced relaxation in endothelium-denuded aorta,
      but its effect was non-additive with Rp-cAMPS, suggesting that the K(+) channel
      component may involve cAMP. In endothelium-intact aortas, TEA but not Rp-cAMPS
      reduced isoprenaline relaxation, suggesting an additional non-cAMP component. 5.
      These findings suggest that beta-adrenoceptors induce vascular smooth muscle
      relaxation by acting through the NO-cGMP pathway and, when that is disrupted by
      endothelium removal or the presence of an NO synthase inhibitor, the cAMP pathway
      in smooth muscles is used. The lack of cAMP participation in endothelium-intact
      vessels may be because NO suppresses or overrides the cAMP effect.

PMID- 17201743
TI  - Genetic polymorphisms of cytochrome P450 enzymes 2C9 and 2C19 in a healthy
      Iranian population.
AB  - 1. The genetically polymorphic cytochrome P450 enzymes 2C9 (CYP2C9) and 2C19
      (CYP2C19) are involved in the metabolism and elimination of a number of widely
      used drugs. The polymorphisms give rise to substantial interindividual and
      interethnic variability in drug excretion rates and final serum concentrations.
      For this reason, therapeutic responses and adverse drug reactions may vary from
      one person to another. In the present study we determined CYP2C9 and CYP2C19
      genotypes in a random Iranian population to compare allele frequencies with
      previous findings in other ethnic groups. 2. Allelic variants of CYP2C9
      (*1/*2/*3) and CYP2C19 (*1/*2/*3) were determined in 200 unrelated healthy
      Iranian volunteers by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) assays. 3. Fifteen subjects (7.5%) were homozygous for
      the CYP2C9*2 allele, whereas 21 individuals (10.5%) were heterozygous for this
      allele and 164 subjects (82%) had the wild-type allele (CYP2C9*1). No CYP2C9*3
      was detected in the population sampled. Six subjects (3%) were homozygous for
      CYP2C19*2, whereas 44 individuals (22%) were heterozygous for this allele. In the
      remaining subjects (75%), no CYP2C19*2 was found. In addition, no CYP2C19*3 was
      detected in the population sampled. 4. Based on our data, the frequency of the
      CYP2C9*2 allelic variant in Iranians is similar to that in other Caucasian
      populations; however, the frequency of the CYP2C9*3 allele differed significantly
      (P < 0.05). Conversely, there was no difference in the frequency of CYP2C19
      allelic variants between the present study and other studies evaluating this
      allele in Caucasian populations (P > 0.05).

PMID- 17201744
TI  - Interactions between metoclopramide and morphine: enhanced antinociception and
      motor dysfunction in rats.
AB  - 1. Opioid analgesics and anti-emetics are often used concomitantly to treat pain
      and nausea and vomiting in people with malignant disease. We investigated
      interactions between the opioid analgesic morphine and the anti-emetic
      metoclopramide, a dopamine D2 receptor antagonist, on nociception and gross motor
      function. 2. To assess for antinociceptive interactions, 11 Sprague-Dawley rats
      were injected intraperitoneally with morphine (5.0 mg/kg) or saline in
      combination with metoclopramide (0.5, 1.5 and 5.0 mg/kg) or saline and, 30 min
      later, the tail-flick latencies to a noxious thermal stimulus (49 degrees C
      water) were measured. Immediately thereafter we induced reperfusion hyperalgesia
      in the rats' tails using a tourniquet cuff and tested nociception again. Because,
      in addition to its ability to block D2 receptors, metoclopramide is also a weak 5
      HT(3) receptor antagonist, we assessed in a further 11 rats whether any
      antinociceptive interactions occurred between morphine (5.0 mg/kg) and
      ondansetron (0.2 and 2.0 mg/kg), an anti-emetic that selectively antagonizes 5
      HT(3) receptors. To assess for motor interactions, we injected another group of
      nine rats with morphine (5.0 mg/kg) or saline in combination with metoclopramide
      (0.5 and 5.0 mg/kg) or saline and tested the ability of the animals to run on an
      80 mm diameter rod rotating at 25 r.p.m. for 30 min. 3. Metoclopramide was not
      inherently analgesic or antihyperalgesic, but the highest dose of metoclopramide
      (5.0 mg/kg) enhanced the analgesic and antihyperalgesic effects of morphine.
      Neither dose of ondansetron was analgesic or antihyperalgesic or enhanced the
      antinociceptive actions of morphine. 4. Only the high dose of metoclopramide
      compromised running performance when administered with saline. However,
      coadministering morphine with metoclopramide (both doses) decreased motor
      performance. 5. Therefore, metoclopramide, possibly through its actions on D2
      receptors and not 5-HT(3) receptors, enhances the analgesic and antihyperalgesic
      effects of morphine, but morphine exacerbates metoclopramide-induced motor
      dysfunction in rats.

PMID- 17201745
TI  - Carnitine palmitoyl transferase-I inhibition is not associated with cardiac
      hypertrophy in rats fed a high-fat diet.
AB  - 1. Cardiac lipotoxicity is characterized by hypertrophy and contractile
      dysfunction and can be triggered by impaired mitochondrial fatty acid oxidation
      and lipid accumulation. The present study investigated the effect of dietary
      fatty acid intake alone and in combination with inhibition of mitochondrial fatty
      acid uptake with the carnitine palmitoyl transferase (CPT)-I inhibitor
      oxfenicine. Long-chain fatty acids activate peroxisome proliferator-activated
      receptors (PPAR), thus mRNA levels of PPAR target genes were measured. 2. Rats
      were untreated or given the CPT-I inhibitor oxfenicine (150 mg/kg per day) and
      were fed for 8 weeks with either: (i) standard low-fat chow (10% of energy from
      fat); (ii) a long-chain saturated fatty acid diet; (iii) a long-chain unsaturated
      fatty acid diet; or (iv) a medium-chain fatty acid diet (which bypasses CPT-I).
      High-fat diets contained 60% of energy from fat. 3. Cardiac triglyceride content
      was increased in the absence of oxfenicine in the saturated fat group compared
      with other diets. Oxfenicine treatment further increased cardiac triglyceride
      stores in the saturated fat group and caused a significant increase in the
      unsaturated fat group. Despite elevations in triglyceride stores, left
      ventricular mass, end diastolic volume and systolic function were unaffected. 4.
      The mRNA levels of PPAR-regulated genes were increased by the high saturated and
      unsaturated fat diets compared with standard chow or the medium chain fatty acid
      chow. Oxfenicine did not further upregulate PPARalpha target genes within each
      dietary treatment group. 5. Taken together, the data suggest that consuming a
      high-fat diet or inhibiting CPT-I do not result in cardiac hypertrophy or cardiac
      dysfunction in normal rats.

PMID- 17201746
TI  - Mechanisms mediating serotonin-induced contraction of colonic myocytes.
AB  - 1. 5-Hydroxytryptamine (5-HT) has an important role in the pathogenesis of
      irritable bowel syndrome. To investigate the effects of 5-HT on the contractile
      activity of myocytes of the guinea-pig proximal colon, cell imaging before and
      after contraction was undertaken and images were analysed using image-analysis
      software. Ion currents and membrane potentials were measured. Cytoplasmic free
      Ca(2+) was recorded using a confocal microscope following loading of the cells
      with the fluorescent probe Fura-2AM. 2. 5-Hydroxytryptamine reduced cell length
      in a dose-dependent manner (EC(50) = 0.189 micromol/L). Under current clamp, 10
      micromol/L 5-HT reduced action potential amplitude (measured as peak height) and
      decreased action potential duration, as well as depolarizing the resting
      potential from -68.4 +/- 3.6 to -22.96 +/- 4.65 mV. Iberiotoxin (1 micromol/L)
      blocked the effects of 5-HT in reducing the time to repolarization (T(90)) and
      nicardipine (5 micromol/L) blocked the effects of 5-HT in reducing action
      potential amplitude. 3. In the whole-cell mode, 5-HT enhanced L-type Ca(2+)
      currents, large conductance K(+) channel (BK(Ca)) currents and spontaneous
      transient outward currents (STOC). In addition, 5-HT increased intracellular
      Ca(2+) levels. Ondansetron (10 micromol/L) blocked the effects of 5-HT in
      enhancing L-type Ca(2+) currents, BK(Ca) currents and STOC. 4. In conclusion, 5
      HT induces contraction of colonic myocytes, mostly as a result of Ca(2+) release
      from the sarcoplasmic reticulum (SR) following activation of 5-HT(3) receptors
      and the inositol 1,4,5-trisphosphate pathway. In addition, the effect of 5-HT in
      decreasing action potential amplitude is mediated by the release of Ca(2+) from
      the SR, as well as by enhanced L-type Ca(2+) current. 5-Hydroxytryptamine
      decreased action potential duration by enhancing BK(Ca) current.

PMID- 17201747
TI  - Comparison of the electrophysiological properties of the sheep isolated costal
      and diaphragmatic parietal pleura.
AB  - 1. Pleural permeability may contribute to pleural fluid turnover. The
      transmesothelial resistance (R(TM)), is an established surrogate of mesothelial
      permeability. The aim of the present study was to compare the
      electrophysiological properties of costal and diaphragmatic parietal pleura. 2.
      Specimens of the parietal pleura were isolated from 12 adult sheep from the chest
      wall and the diaphragm. Electrophysiological measurements were conducted with the
      Ussing system. Specimens of the parietal pleura of both types (diaphragmatic and
      costal) were compared histologically and total protein content measurements were
      also made. 3. The R(TM) of the diaphragmatic parietal pleura was significantly
      higher than that of the costal parietal pleura throughout the experiment. The
      diaphragmatic parietal pleura contains more cuboidal cells than the costal
      parietal pleura and its protein content was higher, however this difference was
      not statistically significant. 4. The costal parietal pleura consists of a more
      'leaky' mesothelium than the diaphragmatic pleura. The morphological differences
      between the two types of parietal pleura may underline the electrophysiological
      findings.

PMID- 17201748
TI  - A mouse model for assessing the impact of ingested nutrients on gastric emptying
      rate.
AB  - 1. The nutrient content of meals can affect the rate of gastric emptying. The aim
      of the present study was to assess whether the gastric emptying breath test could
      detect nutrient-induced delays in gastric emptying. 2. Following ingestion of a
      non-nutrient, carbohydrate- or lipid-containing liquid, mice were placed into
      chambers and breath samples were collected at intervals. Analysis of the rate of
      (13)CO(2) excretion allowed the calculation of gastric half-excretion time. 3.
      Gastric half-excretion time was significantly delayed by the incorporation of
      carbohydrate or lipid into the test liquid. 4. The present study has shown that
      the breath test is sensitive enough to detect changes induced by altering the
      nutrient and caloric content of test meals.

PMID- 17201749
TI  - Coronal sealing ability of three sectional obturation techniques--SimpliFill,
      Thermafil and warm vertical compaction--compared with cold lateral condensation
      and post space preparation.
AB  - The purpose of this study was to evaluate the effect post space preparation has
      on the coronal seal of root canals obturated with cold lateral condensation of
      gutta-percha compared with the corsonal sealing ability of three sectional
      obturation techniques not requiring post space preparation. Sixty-eight human
      maxillary central incisors were divided equally into four groups: cold lateral
      condensation (Group I), SimpliFill (Group II), Thermafil (Group III) and warm
      vertical compaction (Group IV). After coronal flaring, all four groups were
      cleaned and shaped with Lightspeed rotary instruments to a size 60 master apical
      rotary. After obturation Peeso Reamers were used to create a post space for Group
      I, while Groups 2, 3 and 4 incorporated the post space in the obturation
      (sectional technique) and did not require making a post space after obturation.
      The teeth were then stored in 100% humidity for 1 week and then kept in rhodamine
      B fluorescent dye for 3 weeks. The teeth were then split open, and the linear dye
      penetration from a coronal to apical direction (coronal seal) was evaluated with
      a fluorescent light microscope. Statistical analysis showed that Group I (cold
      lateral condensation followed by post space made with Peeso Reamers) leaked
      significantly more (P < 0.05) than the remaining three sectional obturation
      groups. It was concluded that stresses generated during post space preparation
      might be detrimental to the seal obtained by the obturation. Sectional
      obturations with their superior sealing ability offer a viable alternative.

PMID- 17201750
TI  - Visualisation of human dental pulp vasculature by immunohistochemical and
      immunofluorescent detection of CD34: a comparative study.
AB  - CD34 is considered a pan-endothelial cell marker for paraffin-embedded sections.
      In this study, both immunohistochemistry and immunofluorescence were applied in
      human dental pulp specimens of moderate thickness (10 microm) in order to observe
      the vasculature of this tissue using CD34. Both techniques revealed a homogenous
      staining pattern with capillaries and larger vessels showing complete and strong
      membrane staining reflecting the high capacity of the pulp for regeneration and
      response to different stimuli. A novel approach in the identification of the
      pulpal vasculature by Cy5-conjugated anti-CD34 is introduced in this study. By
      this technique the dense capillary plexus of the sub-odontoblastic region, which
      is responsible for the reaction of the tissue to any physical or chemical stimuli
      or pathological condition, can be clearly identified, while immunohistochemistry
      did not reveal such a detailed staining pattern.

PMID- 17201751
TI  - Debris retention and wear in three different nickel-titanium rotary instruments.
AB  - The aim of this in vitro study was to compare three nickel-titanium (Ni-Ti)
      rotary instruments: EndoWave, K3 and ProFile, with respect to their debris
      retention and wear. Thirty simulated root canal models made from resin blocks
      with 40 degrees canal curvature were used. They were divided into three groups of
      10 samples each; EndoWave, K3 and ProFile were used in Groups A, B and C
      respectively. They were prepared with four serial size files. The weight of each
      file was measured to evaluate debris retention and wear at four representative
      time points: prior to root canal preparation (W1), immediately after root canal
      preparation (W2), after ultrasonic cleaning (W3), after further additional
      cleaning (W4). The weight of debris on each file after root canal instrumentation
      and ultrasonic cleaning was calculated as D1: (W2 - W4) and D2: (W3 - W4)
      respectively. Also, wear of the file was calculated as WF: (W1 - W4). There was a
      significant difference in the amount of debris remaining on the file among the
      three files; EndoWave retained more debris (D1) than K3 and ProFile (P < 0.001,
      one-way anova). ProFile had the largest amount of debris (D2) remaining after
      ultrasonic cleaning (P < 0.001). Wear was not detectable in this study. Under the
      conditions of this study, immediately after root canal preparation, EndoWave
      retained the largest amount of debris, while ProFile retained the most debris
      even after ultrasonic cleaning.

PMID- 17201752
TI  - Evaluation of the antibacterial substantivity of several intra-canal agents.
AB  - The aim of this in vitro study was to compare the antimicrobial substantivity of
      2% chlorhexidine gluconate (CHX), 100 mg ml(-1) doxycycline and 2.6% sodium
      hypochlorite (NaOCl) in bovine root dentine. Eighty dentine tubes prepared from
      bovine incisors were infected in vitro for 14 days with Enterococcus faecalis.
      The specimens were divided into five groups as follows: doxycycline HCl; CHX;
      NaOCl; infected dentine tubes (positive control); and sterile dentine tubes
      (negative control). Dentine chips were collected with round burs into tryptic soy
      broth. After culturing, the number of colony-forming units (CFU) was counted. In
      all experimental groups, the number of CFU was minimum in the first cultures, and
      the results obtained were significantly different from each other at any time
      period (P < 0.05). In the first culture, the NaOCl group and doxycycline HCl
      group showed the lowest and highest number of CFU, respectively. In each group,
      the number of CFU increased significantly by time-lapse (P < 0.05). In
      conclusion, the substantivity of CHX was significantly greater than NaOCl and
      doxycycline.

PMID- 17201753
TI  - In vitro computer analysis of crown discolouration from commonly used endodontic
      sealers.
AB  - The aim of this study was to assess the degree of staining of tooth crowns by
      commonly used endodontic sealers using a computer analysis method. Crown
      discolouration by root canal sealers AH26, Endofill, Tubliseal, Zinc oxide
      eugenol (ZnOE), Apatite root canal sealer III as well as gutta-percha and Cavizol
      (a filling material containing ZnOE) were tested on extracted human premolar
      teeth. The roots of the teeth were resected 3 mm below the cemento-enamel
      junction. The pulp chambers were then cleaned and irrigated. The samples were
      divided into nine groups of five samples each and filled with test materials. Ten
      teeth were used as control groups: five positive (amalgam) and five negative
      (distilled water). The degree of tooth discolouration was analysed at 3, 6 and 9
      months. The crown discolouration was assessed by computer analysis of digital
      images taken from the samples using the CIE Lab colour system. Statistical
      analysis was carried out using anova, repeated measure anova and Tukey's HSD
      tests. All sealers caused a degree of tooth discolouration, which increased with
      time. Endofill and ZnOE caused the greatest discolouration and Apatite root canal
      sealer III caused the least discolouration after 9 months. The most
      discolouration during the test periods occurred in the cervical third of the
      crown.

PMID- 17201754
TI  - Evaluation of the antifungal effects of mineral trioxide aggregate materials.
AB  - The aim of this study was to evaluate and compare the antifungal effect of white
      coloured mineral trioxide aggregate (WMTA) and grey mineral trioxide aggregate
      (GMTA) using a tube-dilution test. MTA preparations were freshly mixed and tested
      after 24 h on Candida albicans. The experiment was carried out in 24-well culture
      plates. Fifty wells were used and divided into four experimental groups (freshly
      mixed WMTA, freshly mixed GMTA, 24 h-set WMTA and 24 h-set GMTA) of 10 wells each
      and control groups of five wells each. Plates of Sabouraud dextrose agar mixed
      with C. albicans served as positive control, and Sabouraud dextrose agar without
      C. albicans served as negative control. Fresh inoculate of C. albicans was
      prepared by growing an overnight culture from a stock culture. Aliquots of C.
      albicans were then taken from the stock culture and plated on the agar compound
      of the experimental and control groups. All plates were incubated at 37 degrees C
      for 1, 24 and 72 h. Growth of fungi was monitored daily by the presence of
      turbidity. Results showed that in the freshly mixed as well as 24 h-set MTA
      cements fungal growth was observed during 1-h incubation, whereas by increasing
      the incubation time, no fungal growth was observed in 24 and 72 h. It was
      concluded that MTA cements (freshly mixed and 24-h set) were effective against C.
      albicans.

PMID- 17201755
TI  - In vitro evaluation of endodontic debris removal as obtained by rotary
      instrumentation coupled with ultrasonic irrigation.
AB  - The cleaning capacity of rotary Ni-Ti instrumentation using Profile GT files,
      coupled with irrigation energised by ultrasound, was evaluated. Thirty-six human
      mandibular incisors were instrumented in vitro using the crown-down technique
      with the Profile GT system to 1 mm from the anatomical apex to a size 30.04 taper
      file. The instrumented teeth were then divided randomly into four groups where
      various final irrigations were used: Group I: 100 ml of 1% NaOCl with a Luer-Lok
      syringe (control group); Group II, Group III and Group IV: final irrigation with
      100 ml of 1% NaOCl energised by ultrasound for 1, 3 and 5 min, respectively.
      After biomechanical preparation, the apical thirds of the roots were submitted to
      histological processing and examination. The specimens were analysed at 40x
      magnification and the images submitted to morphometric analysis with an
      integration grid. anova showed a statistically significant difference (P < 0.01)
      between the irrigation techniques. Group I (Luer-Lok syringe) showed the highest
      percentage of debris (35.81 +/- 4.49) and was statistically different from the
      other groups energised by ultrasound: Group II (27.28 +/- 4.49), Group III (24.39
      +/- 5.72) and Group IV (18.46 +/- 5.25). It was concluded that rotary
      instrumentation using Ni-Ti files associated with final irrigation of 1% NaOCl
      energised by ultrasound leads to better debris removal from the apical third of
      mesio-distally flattened root canal.

PMID- 17201756
TI  - Endodontic retreatment of a maxillary second molar with three separate buccal
      roots.
AB  - A rare case of a four-rooted maxillary second molar in a 39-year-old male patient
      is reported. After clinical and radiographic examination, two separate mesio
      buccal roots were detected, and a treatment plan consisting treatment of the
      mesio-buccal roots and retreatment of the disto-buccal and palatal roots was made
      to resolve the previous treatment failure. The tooth was treated by orthograde
      endodontic retreatment in two visits. Mesio-buccal canals that were located in
      the separate mesio-buccal roots (which were missed in previous treatment) were
      found and treated. The case report underlines the importance of complete
      knowledge about root canal morphology and possible variations, coupled with full
      clinical and radiographic examination, in order to increase the ability of
      clinicians to treat difficult cases.

PMID- 17201759
TI  - Letter to the president of the Australian Society of Endodontology.

PMID- 17201765
TI  - Expression of immune responsive genes in cell lines from two different Anopheline
      species.
AB  - Malaria infection results in increased expression of immune responsive genes,
      including those encoding antimicrobial peptides such as Gambicin (Gam1) and
      Cecropin A (Cec1). Understanding how these genes are regulated will provide
      insights how the mosquito immune system is activated by Plasmodium. We previously
      have shown that Cec1 was primarily regulated by the Imd-Relish (REL2) pathway in
      the Anopheles gambiae Sua1B cell line. We show here that expression of Defensin A
      (Def1) and Gam1 was reduced after RNA interference against components of the Imd
      REL2 pathway in An. gambiae cell lines. Interestingly, promoter reporters of
      these antimicrobial peptides were expressed at very low level in the cell line
      MSQ43 from Anopheles stephensi. Surprisingly, over-expression of either NF-kappaB
      transcription factor REL1 or REL2 alone is sufficient to induce the expression of
      Cec1, Gam1 and Def1. These results suggest that expression of these antimicrobial
      peptides (AMP) in vivo may be regulated by both the Toll and Imd pathways. We
      also show here for the first time that Tep4, a gene encoding a thioester
      containing protein, is regulated by REL2. Taken together, these results suggest
      that there are significant overlaps of genes regulated by the Toll-Rel1 and Imd
      Rel2 pathways. Further, the different expression patterns in two different
      Anopheline cell lines provide a platform to identify other key positive and
      negative regulators of the antimicrobial peptide genes.

PMID- 17201766
TI  - 'Suicide' of crickets harbouring hairworms: a proteomics investigation.
AB  - Despite increasing evidence of host phenotypic manipulation by parasites, the
      underlying mechanisms causing infected hosts to act in ways that benefit the
      parasite remain enigmatic in most cases. Here, we used proteomics tools to
      identify the biochemical alterations that occur in the head of the cricket
      Nemobius sylvestris when it is driven to water by the hairworm Paragordius
      tricuspidatus. We characterized host and parasite proteomes during the expression
      of the water-seeking behaviour. We found that the parasite produces molecules
      from the Wnt family that may act directly on the development of the central
      nervous system (CNS). In the head of manipulated cricket, we found differential
      expression of proteins specifically linked to neurogenesis, circadian rhythm and
      neurotransmitter activities. We also detected proteins for which the function(s)
      are still unknown. This proteomics study on the biochemical pathways altered by
      hairworms has also allowed us to tackle questions of physiological and molecular
      convergence in the mechanism(s) causing the alteration of orthoptera behaviour.
      The two hairworm species produce effective molecules acting directly on the CNS
      of their orthoptera hosts.

PMID- 17201767
TI  - Intact mariner-like element in tobacco budworm, Heliothis virescens (Lepidoptera:
      Noctuidae).
AB  - An intact mariner-like element was isolated from the genome of tobacco budworm,
      Heliothis virescens. This is the first report of an intact mariner element after
      the initial identification of Mos1 from Drosophila mauritiana. The full-length
      Hvmar1 has 30 bp inverted terminal repeats and a complete 1065 bp open reading
      frame (ORF) encoding the transposase with a 'D,D(34)D' motif in the catalytic
      domain. Polymerase chain reaction results show that at least one insertion of the
      Hvmar1 element is conserved in this Heliothis strain. Phylogenetic analysis
      demonstrated that Hvmar1 belongs to the irritans subfamily.

PMID- 17201768
TI  - Juvenile hormone and colony conditions differentially influence cytochrome P450
      gene expression in the termite Reticulitermes flavipes.
AB  - In lower termites, the worker caste is a totipotent immature stage that is
      capable of differentiating into other adult caste phenotypes. We investigated the
      diversity of family 4 cytochrome P450 (CYP4) genes in Reticulitermes flavipes
      workers, with the specific goal of identifying P450s potentially involved in
      regulating caste differentiation. Seven novel CYP4 genes were identified.
      Quantitative real-time PCR revealed the tissue distribution of expression for the
      seven CYP4s, as well as temporal expression changes in workers in association
      with a release from colony influences and during juvenile hormone (JH)-induced
      soldier caste differentiation. Several fat-body-related CYP4 genes were
      differentially expressed after JH treatment. Still other genes changed expression
      in association with removal from colony influences, suggesting that primer
      pheromones and/or other colony influences impact their expression. These findings
      add to a growing database of candidate termite caste-regulatory genes, and
      provide explicit evidence that colony factors influence termite gene expression.

PMID- 17201769
TI  - Molecular cloning and heterologous expression of an alpha-adrenergic-like
      octopamine receptor from the silkworm Bombyx mori.
AB  - A cDNA encoding an octopamine (OA) receptor (BmOAR1) was isolated from the nerve
      tissue of silkworm (Bombyx mori) larvae. Comparison of amino acid sequences
      showed that BmOAR1 is highly identical to OA receptors isolated from Periplaneta
      americana (Pa oa(1)), Apis mellifera (AmOA1), and Drosophila melanogaster (OAMB
      or DmOA1A). BmOAR1 was stably expressed in HEK-293 cells. OA above 1 microM led
      to an increase in intracellular cyclic AMP concentration ([cAMP](i)). The
      synthetic OA-receptor agonist demethylchlordimeform also elevated [cAMP](i) to
      the same maximal level (approximately 5-fold over the basal level) as that
      induced by OA. However, other biogenic amines, tyramine and dopamine, and
      chlordimeform were without effects. The [cAMP](i) level raised by OA was lowered
      by antagonists; the rank order of antagonist activity was chlorpromazine >
      mianserin = yohimbine. Cyproheptadine and metoclopramide had little effect. OA
      above 100 nM induced a transient or sustained increase in intracellular Ca(2+)
      concentration ([Ca(2+)](i)), depending on the concentration of OA. Sequence
      homology and functional analysis data indicate that BmOAR1 is an alpha-adrenergic
      like OA receptor of B. mori.

PMID- 17201770
TI  - Functional characterization of Musca glutamate- and GABA-gated chloride channels
      expressed independently and coexpressed in Xenopus oocytes.
AB  - Ligand-gated chloride channels (LGICs) are important targets for insecticides and
      parasiticides. Genes encoding subunits of two LGICs, a glutamate-gated chloride
      channel (MdGluCl-alpha) and a gamma-aminobutyric acid (GABA)-gated chloride
      channel (MdRdl), were cloned from house-flies (Musca domestica L.). These genes
      were first expressed independently in Xenopus laevis oocytes by cRNA injection in
      order to investigate the pharmacology of these ligand-gated channels using two
      electrode voltage-clamp electrophysiology. It was found that L-glutamate and GABA
      activated the MdGluCl-alpha homo-oligomers with an EC(50) value of 30 microM and
      the MdRdl homo-oligomers with an EC(50) value of 101 microM, respectively. Both
      channels were chloride ion-permeable, and the MdRdl channel was more sensitive to
      chloride channel blockers, such as gamma-hexachlorocyclohexane (gamma-HCH),
      fipronil and picrotoxinin, than the MdGluCl-alpha channel. MdGluCl-alpha required
      only 1-2 days of incubation after cRNA injection to be expressed in oocytes,
      whereas 4-7 days of incubation was necessary to achieve MdRdl expression.
      However, when the cRNA of MdGluCl-alpha was injected at a dose of 1% (w/w) 1 day
      after the injection of the cRNA of MdRdl, a significant increase in the current
      amplitude of responses to GABA was observed, and the incubation period necessary
      for MdRdl expression became shorter. These results suggest that MdGluCl-alpha
      assists in the expression of MdRdl when the two are coexpressed.

PMID- 17201771
TI  - Analysis of transcriptional activity mediated by Drosophila melanogaster ecdysone
      receptor isoforms in a heterologous cell culture system.
AB  - Ecdysteroid regulation of gene transcription in Drosophila melanogaster and other
      insects is mediated by a heterodimer comprised of Ultraspiracle (USP) and one of
      three ecdysone receptor (EcR) isoforms (A, B1 and B2). This study revealed that
      the EcR/USP heterodimer displays isoform-specific capabilities. EcRB1 is normally
      induced with a form of USP that is missing its DNA-binding domain (DBD), although
      potentiation by juvenile hormone (JH) III is reduced. The EcRA and B2 isoforms,
      however, display almost no response to ecdysteroids with the DBD(-) USP. A
      mutation, K497E, in the shared ligand-binding domain of the EcR isoforms caused
      elevated EcRB2-specific affinity for a canonical ecdysone response element. The
      effects of directed modification and mutagenesis offer a strategy for developing
      hypotheses and considerations for studying in vivo function.

PMID- 17201772
TI  - Specific interactions among odorant-binding proteins of the African malaria
      vector Anopheles gambiae.
AB  - In this report we present results from a comprehensive study undertaken toward
      the identification of proteins interacting with odourant-binding proteins (OBPs)
      of the African malaria vector Anopheles gambiae with a focus on the interactions
      among different OBPs. From an initial screen for proteins that interact with a
      member of the Plus-C group of OBPs, OBP48, which is primarily expressed in female
      antennae and downregulated after a blood meal, a number of interacting proteins
      were identified, which included five classic OBPs and OBP48 itself. The
      interacting OBPs as well as a number of other classic and Plus-C group OBPs that
      were not identified in the initial screen, were expressed in lepidopteran cells
      and subsequently examined for in vitro interactions in the absence of exogenously
      added ligands. Co-immunoprecipitation and chemical cross-linking studies suggest
      that OBP48 is capable of homodimerizing, heterodimerizing and forming higher
      order complexes with those examined examples of classical OBPs identified in the
      initial screen but not with other classical or Plus-C group OBPs that failed to
      appear in the screen. The latter OBPs are, however, also capable of forming
      homodimers in vitro and, at least in the case of two examined classic OBPs,
      heterodimers as well. These results suggest a previously unsuspected potential of
      nonrandom combinatorial complexity that may be crucial for odour discrimination
      by the mosquito.

PMID- 17201773
TI  - Structure and expression of a novel gene family showing male germline specific
      expression in Drosophila melanogaster.
AB  - We report the characterization of two novel genes of Drosophila melanogaster,
      named mst36Fa and mst36Fb. They define a novel gene family, showing identical
      time and tissue-specificity limited to male germ cells where their transcription
      starts during meiotic prophase. These two genes encode for two slightly basic
      proteins highly homologous to each other and fairly rich in leucine and glutamic
      acid. Although strictly clustered, these genes utilize different promoter regions
      as revealed by examination of transgenic flies bearing mst36F-promoter-lacZ
      reporter constructs and by reverse transcription-polymerase chain reaction
      assays. Our data suggest that at least one gene (mst36Fa) of the cluster is under
      translational repression until spermiogenesis suggesting a putative role in the
      spermatides differentiation. The present study is aimed at the structural
      analysis of these genes.

PMID- 17201774
TI  - Cathepsin L function in insect moulting: molecular cloning and functional
      analysis in cotton bollworm, Helicoverpa armigera.
AB  - Moulting is an essential process of insect development but little is known about
      cysteine proteases in the process. Here, we detail a proteolytic activity profile
      from fifth larval instar to new pupae of the lepidopteran Helicoverpa armigera.
      At fifth to sixth instar moulting, the activities were significantly higher than
      those in non-moulting stages, and were inhibited by the cysteine protease
      inhibitor, 2S, 3S-trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester (E
      64), or by the cathepsin L-selective inhibitor CLIK148. Further, a 1513 bp
      cathepsin L cDNA (Har-CL) was isolated from the H. armigera larval cuticle and
      epidermis layer. Har-CL gene expression, which is correlated closely with
      ecdysone, was higher during larval moulting. Injection of E-64 or CLIK148
      resulted in delayed fifth to sixth instar moulting, suggesting an essential role
      for cathepsin L in larval moulting.

PMID- 17201775
TI  - Use of quantitative real-time polymerase chain reaction to estimate the size of
      the house-fly Musca domestica genome.
AB  - House-flies, Musca domestica, are carriers of more than 100 devastating diseases
      that have severe consequences for human and animal health. A key bottleneck to
      progress in controlling the devastating human diseases transmitted by house-flies
      is lack of knowledge of the basic molecular biology of this species. However,
      before sequencing of the house-fly genome can be seriously considered it is
      important to know the size of the genome. In this paper, we used quantitative
      real-time polymerase chain reaction to calculate genome size of the house-fly in
      side-by-side experiments with Drosophila melanogaster (known genome size of 180
      Mb). Our results indicate the size of the house-fly genome is 295 +/- 10 Mb and
      that of D. melanogaster is 184 Mb. Thus, the house-fly genome is only about 1.6
      fold larger than the genome of D. melanogaster. This indicates that the size of
      the house-fly genome makes it an excellent candidate for whole genome sequencing
      and that quantitative real-time polymerase chain reaction is an accurate method
      for the estimation of the size of insect genomes.

PMID- 17201776
TI  - cDNA cloning, heat shock regulation and developmental expression of the hsp83
      gene in the Mediterranean fruit fly Ceratitis capitata.
AB  - This report presents the cDNA cloning, heat shock regulation and developmental
      expression of the hsp90 gene homologue of the Mediterranean fruit fly Ceratitis
      capitata (medfly). The isolated cDNA contained the coding region, the 3'UTR and
      most of the 5'UTR of the medfly hsp90 homologue, which was named Cchsp83. The
      deduced CcHSP83 polypeptide contained all the highly conserved amino acid
      segments that characterize the cytosolic members of the HSP90 family. Genomic
      analysis showed that the Cchsp83 gene is unique and was mapped at the 94C
      division of the sixth polytene chromosome. The size of the Cchsp83 mRNA was found
      to be approximately 2.7 kb. The predicted molecular mass of the CcHSP83 protein
      was 81.4 kDa, while the apparent molecular weight estimated by SDS-PAGE was
      approximately 90 kDa. Phylogenetic analysis based on 14 insect HSP90 amino acid
      sequences was consistent with the known phylogeny at low taxonomic level. The
      Cchsp83 gene is constitutively expressed in all stages of medfly development and
      is induced from a low level to several-fold by heat, depending on the
      developmental stage. Heat shock induction begins at 30 degrees C, reaching a
      maximum between 35 and 41 degrees C. Cchsp83 RNA expression is highly regulated
      during embryonic development; however, the temporal fluctuations in RNA levels
      during embryogenesis were not followed by similar fluctuations in the levels of
      the protein.

PMID- 17201777
TI  - Methionine-rich storage protein gene in the rice stem borer, Chilo suppressalis,
      is expressed during diapause in response to cold acclimation.
AB  - Gene expressions of acclimatized and non-acclimatized diapausing larvae were
      examined in Chilo suppressalis using a subtraction technique. A gene encoding a
      methionine-rich storage protein, CsSP1, was cloned and its complete cDNA sequence
      was determined. Potentially, CsSP1 encoded a 758-amino acid protein, with a
      calculated molecular weight of 88.8 kDa. The expression level of CsSP1 was higher
      in nondiapausing larvae than in diapausing ones. The CsSP1 expression was up
      regulated in diapausing larvae when the temperature of cold acclimation was
      shifted to 5 degrees C. The up-regulated level was maintained at 40 days after
      incubation at 5 degrees C. In nondiapausing larvae, CsSP1 expression was down
      regulated when the temperature was below developmental zero. Involvement of CsSP1
      in diapause, cold tolerance acquisition and postdiapause development in C.
      suppressalis is discussed.

PMID- 17201779
TI  - Vision following extended congenital blindness.
AB  - Animal studies suggest that early visual deprivation can cause permanent
      functional blindness. However, few human data on this issue exist. Given enough
      time for recovery, can a person gain visual skills after several years of
      congenital blindness? In India, we recently had an unusual opportunity to work
      with an individual whose case history sheds light on this question. S.R.D. was
      born blind, and remained so until age 12. She then underwent surgery for the
      removal of dense congenital cataracts. We evaluated her performance on an
      extensive battery of visual tasks 20 years after surgery. We found that although
      S.R.D.'s acuity is compromised, she is proficient on mid- and high-level visual
      tasks. These results suggest that the human brain retains an impressive capacity
      for visual learning well into late childhood. They have implications for current
      conceptions of cortical plasticity and provide an argument for treating
      congenital blindness even in older children.

PMID- 17201780
TI  - Object substitution masking interferes with semantic processing: evidence from
      event-related potentials.
AB  - Object substitution masking (OSM) refers to impaired target identification caused
      by common onset, but delayed offset, of a surrounding dot mask. This effect has
      been hypothesized to reflect reentrant processes that result in the mask
      replacing the target representation. However, little is known about the depth of
      processing associated with masked targets in this paradigm. We investigated this
      issue by examining the effect of OSM on the N400 component of the event-related
      potential, which reflects the degree of semantic mismatch between a target and
      its context. Participants read a context word followed by a semantically related
      or unrelated target word surrounded by dots. As expected, delayed dot offset
      significantly reduced accuracy in identifying the target. The N400 amplitude was
      also diminished by OSM. These findings offer the first evidence that substitution
      interferes with target processing prior to semantic analysis, demonstrating an
      important difference between OSM and other visual phenomena, such as the
      attentional blink, in which semantic processing is independent of awareness.

PMID- 17201781
TI  - The time course of orthographic and phonological code activation.
AB  - The present study used event-related potentials (ERPs) to examine the time course
      of orthographic and phonological priming in the masked priming paradigm.
      Participants monitored visual target words for occasional animal names, and ERPs
      to nonanimal critical items were recorded. These critical items were preceded by
      different types of primes: Orthographic priming was examined using transposed
      letter (TL) primes (e.g., barin-BRAIN) and their controls (e.g., bosin-BRAIN);
      phonological priming was examined using pseudohomophone primes (e.g., brane
      BRAIN) and their controls (e.g., brant-BRAIN). Both manipulations modulated the
      N250 ERP component, which is hypothesized to reflect sublexical processing during
      visual word recognition. Orthographic (TL) priming and phonological
      (pseudohomophone) priming were found to have distinct topographical distributions
      and different timing, with orthographic effects arising earlier than phonological
      effects.

PMID- 17201782
TI  - Satisfaction guaranteed: the effect of spatial biases on responses to likert
      scales.

PMID- 17201783
TI  - The neglect of musicians: line bisection reveals an opposite bias.

PMID- 17201784
TI  - Lending a hand: social regulation of the neural response to threat.
AB  - Social contact promotes enhanced health and well-being, likely as a function of
      the social regulation of emotional responding in the face of various life
      stressors. For this functional magnetic resonance imaging (fMRI) study, 16
      married women were subjected to the threat of electric shock while holding their
      husband's hand, the hand of an anonymous male experimenter, or no hand at all.
      Results indicated a pervasive attenuation of activation in the neural systems
      supporting emotional and behavioral threat responses when the women held their
      husband's hand. A more limited attenuation of activation in these systems
      occurred when they held the hand of a stranger. Most strikingly, the effects of
      spousal hand-holding on neural threat responses varied as a function of marital
      quality, with higher marital quality predicting less threat-related neural
      activation in the right anterior insula, superior frontal gyrus, and hypothalamus
      during spousal, but not stranger, hand-holding.

PMID- 17201785
TI  - Sex differences in intellectual performance: analysis of a large cohort of
      competitive chess players.
AB  - Only 1% of the world's chess grandmasters are women. This underrepresentation is
      unlikely to be caused by discrimination, because chess ratings objectively
      reflect competitive results. Using data on the ratings of more than 250,000
      tournament players over 13 years, we investigated several potential explanations
      for the male domination of elite chess. We found that (a) the ratings of men are
      higher on average than those of women, but no more variable; (b) matched boys and
      girls improve and drop out at equal rates, but boys begin chess competition in
      greater numbers and at higher performance levels than girls; and (c) in locales
      where at least 50% of the new young players are girls, their initial ratings are
      not lower than those of boys. We conclude that the greater number of men at the
      highest levels in chess can be explained by the greater number of boys who enter
      chess at the lowest levels.

PMID- 17201787
TI  - Try it, you'll like it: the influence of expectation, consumption, and revelation
      on preferences for beer.
AB  - Patrons of a pub evaluated regular beer and "MIT brew" (regular beer plus a few
      drops of balsamic vinegar) in one of three conditions. One group tasted the
      samples blind (the secret ingredient was never disclosed). A second group was
      informed of the contents before tasting. A third group learned of the secret
      ingredient immediately after tasting, but prior to indicating their preference.
      Not surprisingly, preference for the MIT brew was higher in the blind condition
      than in either of the two disclosure conditions. However, the timing of the
      information mattered substantially. Disclosure of the secret ingredient
      significantly reduced preference only when the disclosure preceded tasting,
      suggesting that disclosure affected preferences by influencing the experience
      itself, rather than by acting as an independent negative input or by modifying
      retrospective interpretation of the experience.

PMID- 17201786
TI  - Motion-perception deficits and reading impairment: it's the noise, not the
      motion.
AB  - We tested the hypothesis that deficits on sensory-processing tasks frequently
      associated with poor reading and dyslexia are the result of impairments in
      external-noise exclusion, rather than motion perception or magnocellular
      processing. We compared the motion-direction discrimination thresholds of adults
      and children with good or poor reading performance, using coherent-motion
      displays embedded in external noise. Both adults and children who were poor
      readers had higher thresholds than their respective peers in the presence of high
      external noise, but not in the presence of low external noise or when the signal
      was clearly demarcated. Adults' performance in high external noise correlated
      with their general reading ability, whereas children's performance correlated
      with their language and verbal abilities. The results support the hypothesis that
      noise-exclusion deficits impair reading and language development and suggest that
      the impact of such deficits on the development of reading skills changes with
      age.

PMID- 17201788
TI  - Stages of abstraction and exemplar memorization in pigeon category learning.
AB  - It has been proposed that human category learning consists of an early
      abstraction-based stage followed by a later exemplar-memorization stage. To
      investigate whether similar processing stages extend to category learning in a
      nonverbal species, we applied a prototype-exception paradigm to investigating
      pigeon category learning. Five birds and 8 humans learned six-dimensional
      perceptual categories constructed to include prototypes, typical items, and
      exceptions. We evaluated the birds' and humans' categorization strategies at
      different points during learning. Early on in both species, prototype performance
      improved rapidly as exception performance remained below chance, indicating an
      initial mastery of the categories' general structure. Later on, exception
      performance improved selectively and dramatically, indicating exception-item
      resolution and exemplar memorization. Abstraction- and exemplar-based formal
      models reinforced these interpretations. The results suggest a psychological
      transition in pigeon category learning from abstraction- to exemplar-based
      processing similar to that found in humans.

PMID- 17201789
TI  - Power and perspectives not taken.
AB  - Four experiments and a correlational study explored the relationship between
      power and perspective taking. In Experiment 1, participants primed with high
      power were more likely than those primed with low power to draw an E on their
      forehead in a self-oriented direction, demonstrating less of an inclination to
      spontaneously adopt another person's visual perspective. In Experiments 2a and
      2b, high-power participants were less likely than low-power participants to take
      into account that other people did not possess their privileged knowledge, a
      result suggesting that power leads individuals to anchor too heavily on their own
      vantage point, insufficiently adjusting to others' perspectives. In Experiment 3,
      high-power participants were less accurate than control participants in
      determining other people's emotion expressions; these results suggest a power
      induced impediment to experiencing empathy. An additional study found a negative
      relationship between individual difference measures of power and perspective
      taking. Across these studies, power was associated with a reduced tendency to
      comprehend how other people see, think, and feel.

PMID- 17201790
TI  - Scaling of theory-of-mind understandings in Chinese children.
AB  - Prior research demonstrates that understanding of theory of mind develops at
      different paces in children raised in different cultures. Are these differences
      simply differences in timing, or do they represent different patterns of cultural
      learning? That is, to what extent are sequences of theory-of-mind understanding
      universal, and to what extent are they culture-specific? We addressed these
      questions by using a theory-of-mind scale to examine performance of 140 Chinese
      children living in Beijing and to compare their performance with that of 135
      English-speaking children living in the United States and Australia. Results
      reveal a common sequence of understanding, as well as sociocultural differences
      in children's developing theories of mind.

PMID- 17201791
TI  - The role of conscious reasoning and intuition in moral judgment: testing three
      principles of harm.
AB  - Is moral judgment accomplished by intuition or conscious reasoning? An answer
      demands a detailed account of the moral principles in question. We investigated
      three principles that guide moral judgments: (a) Harm caused by action is worse
      than harm caused by omission, (b) harm intended as the means to a goal is worse
      than harm foreseen as the side effect of a goal, and (c) harm involving physical
      contact with the victim is worse than harm involving no physical contact. Asking
      whether these principles are invoked to explain moral judgments, we found that
      subjects generally appealed to the first and third principles in their
      justifications, but not to the second. This finding has significance for methods
      and theories of moral psychology: The moral principles used in judgment must be
      directly compared with those articulated in justification, and doing so shows
      that some moral principles are available to conscious reasoning whereas others
      are not.

PMID- 17201792
TI  - Persistent difference in short-term memory span between sign and speech:
      implications for cross-linguistic comparisons.

PMID- 17201793
TI  - No difference in short-term memory span between sign and speech.

PMID- 17201794
TI  - Epidemiology of non-gastroenteropancreatic (neuro)endocrine tumours.
AB  - The widespread availability and reliability of immunohistochemical techniques in
      the last three decades have allowed researchers to identify cells with common
      neuroendocrine markers in virtually every organ. As a whole, these neuroendocrine
      cells form the so-called diffuse neuroendocrine system. Tumours arising from the
      cells of the diffuse neuroendocrine system are defined as (neuro)endocrine
      tumours (NETs). NETs have been increasingly described in recent years. However,
      despite the increase in the number of published papers focused on NET, we still
      lack adequate epidemiological data, particularly for non-gastroenteropancreatic
      (GEP) NETs. Furthermore, the real incidence of neuroendocrine differentiation for
      most sites is not completely known and is probably underestimated. As a
      consequence, data on the clinical features of many NET subgroups are not well
      known or confusing. For all of these reasons, we have attempted to evaluate the
      epidemiology of non-GEP NETs, reviewing the limited data available in the
      literature.

PMID- 17201795
TI  - Abnormal expression of PPAR gamma isoforms in the subcutaneous adipose tissue of
      patients with Cushing's disease.
AB  - BACKGROUND: Obesity is a clinical feature of patients with Cushing's disease.
      Peroxisome proliferators-activated receptor (PPAR)gamma is the master regulator
      of adipogenesis; however, the expression of PPARgamma isoforms in the
      subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown.
      AIM AND METHODS: The expression of PPARgamma1 and PPARgamma2 was evaluated by
      real-time reverse transcription polymerase chain reaction (RT-PCR) and
      immunofluorescence (PPARgamma2 only) in SAT samples of 7 patients with untreated
      active Cushing's disease (Cushing(UNTR)), 8 with Cushing's disease in remission
      (Cushing(REM)) after pituitary adenomectomy, 15 normal lean subjects
      (Control(LEAN)), and 15 obese patients (Control(OBE)). RESULTS: Control(LEAN) had
      a higher degree of PPARgamma1 than PPARgamma2 (PPARgamma2/PPARgamma1 ratio, 0.55
      +/- 0.35). PPARgamma2/PPARgamma1 ratio decreased in Cushing(UNTR) (0.10 +/-
      0.043, P < 0.03 vs. Control(LEAN) and Control(OBE)), because of either increased
      PPARgamma1 or reduced PPARgamma2 expression. PPARgamma2/PPARgamma1 ratio was 0.48
      +/- 0.07 in Cushing(REM) patients (P < 0.04 vs. Cushing(UNTR), P < 0.03 vs.
      Control(OBE)). PPARgamma2/PPARgamma1 ratio was higher in Control(OBE) 0.90 +/-
      0.38 than in Control(LEAN) (P < 0.005 vs. Control(LEAN), P < 0.03 vs.
      Cushing(REM), P < 0.009 vs. Cushing(UNTR)). PPARgamma2/PPARgamma1 ratio was
      related to serum cortisol levels only in patients with Cushing'disease (r =
      0.688, P < 0.02). CONCLUSIONS: Cushing(UNTR) patients had an abnormal expression
      of PPARgamma isoforms in SAT related to serum cortisol levels. Although further
      studies are necessary, it is conceivable that variations in the expression of
      PPARgamma isoforms might have a role in the abnormal adipogenesis of patients
      with Cushing's disease.

PMID- 17201796
TI  - Combined clinical, thyroid ultrasound and cytological features help to predict
      thyroid malignancy in follicular and Hupsilonrthle cell thyroid lesions: results
      from a series of 505 consecutive patients.
AB  - OBJECTIVE: The cytological patterns of follicular and Hupsilonrthle cell nodules
      are included among the indeterminate results of fine-needle aspiration cytology,
      because distinction between benign and malignant lesion can only be made on
      histological criteria. The diagnostic value of atypia at cytology, clinical
      parameters and echographic patterns were examined to establish the risk of
      malignancy in 505 patients with follicular and Hupsilonrthle cell thyroid nodules
      at cytology. DESIGN AND PATIENTS: The study included 505 consecutive patients who
      had undergone thyroidectomy from the period 2002-2005. RESULTS: Histological
      diagnosis of malignancy was carried out in 125 of 505 (25%) patients, the
      follicular variant of papillary carcinoma being the most frequent histotype. Only
      atypia at cytology (P < 0.0001) and spot microcalcifications at ultrasound (P =
      0.009) were predictive of malignancy. Male gender, normal thyroid volume, single
      nodularity, nodule hypoechogenicity, size and blurred margins were associated
      with malignancy, although not significantly. An arbitrary clinical score allowed
      the identification of patients with high (41%, 110 patients) and low (16%, 242
      patients) risk of malignancy. Combining the clinical score with the presence of
      atypia at cytology we could identify 30 patients (6%) in whom the risk of
      malignancy was as high as 63%. CONCLUSIONS: Twenty-five per cent of patients with
      a cytological result of follicular and Hupsilonrthle cell thyroid lesion had a
      final diagnosis of malignancy. Only atypia at cytology and spot
      microcalcifications at thyroid ultrasound were significantly associated with
      malignancy. Other clinical parameters and thyroid ultrasound patterns can be used
      to set up a clinical score useful for predicting the individual risk of
      malignancy before surgery.

PMID- 17201797
TI  - Functional characterization of a novel insulin receptor mutation contributing to
      Rabson-Mendenhall syndrome.
AB  - OBJECTIVE/PATIENTS: Rabson-Mendenhall syndrome (RMS) is a rare, recessively
      inherited disorder of extreme insulin resistance due to mutations in the insulin
      receptor gene. We have identified a pair of siblings with RMS attributable to
      compound heterozygosity for two insulin receptor mutations, one previously
      unreported, and have characterized the novel receptor mutation functionally.
      MEASUREMENTS: Insulin receptor sequencing was performed to identify the
      mutations. Expression levels of the mature receptor were determined in
      lymphoblastoid cells from the affected subjects. Further studies of immortalized
      cell lines transfected with mutant and wild type (WT) receptors were undertaken
      to characterize the effects of the novel mutation on [(125)I]-labelled insulin
      binding, proreceptor processing and insulin-stimulated receptor
      autophosphorylation. RESULTS: Sequencing of the insulin proreceptor coding
      sequence revealed both siblings to be compound heterozygotes for the missense
      mutations Arg209His and Gly359Ser in the mature insulin receptor. The former
      mutation has been described in homozygous form in Donohue syndrome, while the
      latter is novel. Insulin receptor expression in lymphoblastoid cell lines was
      present at only 10-30% of that in control cells; studies of immortalized cells
      transfected with mutant and WT receptors confirmed the reduced expression of the
      mutant. The degree of impairment of insulin binding and insulin-stimulated
      receptor autophosphorylation were commensurate with the decrease in expression of
      the mature receptor. CONCLUSIONS: Loss of function of the novel insulin receptor
      (INSR) G359S variant is largely accounted for by aberrant proreceptor processing
      rather than intrinsically impaired signal transduction by the mutant receptor.

PMID- 17201798
TI  - Effects of low-dose continuous combined hormone replacement therapy on glucose
      homeostasis and markers of cardiovascular risk in women with type 2 diabetes.
AB  - BACKGROUND: Low-dose hormone replacement therapy (HRT) has attracted interest for
      the treatment of postmenopausal symptoms in diabetes because of concerns about
      increased risk of coronary heart disease (CHD) and stroke with conventional HRT
      containing conjugated equine oestrogens (CEEs) and medroxyprogesterone acetate
      (MPA). OBJECTIVES: We assessed the effects on glucose homeostasis and
      cardiovascular risk factors of continuous oral 17beta oestradiol (1 mg) and
      norethisterone (0.5 mg) in postmenopausal women with type 2 diabetes. DESIGN:
      Double-blind, randomized placebo-controlled trial. ASSESSMENTS: Hyperinsulinaemic
      isoglycaemic clamp and cardiovascular risk factors were assessed before and after
      3 months of treatment. RESULTS: Twenty-eight women completed the study. HRT
      decreased fasting glucose compared with placebo [-9.4% with HRT vs.+2.3% for
      placebo, 95% confidence interval (CI) -23.2 to -0.3] and total cholesterol (-13.7
      vs.+1.0%, 95% CI -22.4 to -3.1%) No significant effect was seen on metabolic
      clearance rate of glucose, glycated haemoglobin (HbA1c), triglycerides, high
      density lipoprotein (HDL)-cholesterol or C-reactive protein (CRP). CONCLUSIONS:
      In women with type 2 diabetes, low-dose HRT decreased fasting glucose and total
      cholesterol without detectable adverse effects on glucose clearance,
      triglycerides and CRP as reported with conventional HRT.

PMID- 17201799
TI  - Plasma 1,25-dihydroxyvitamin D levels in primary hyperparathyroidism depend on
      sex, body mass index, plasma phosphate and renal function.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is characterized by elevated
      plasma levels of PTH and calcium with reduced plasma phosphate. Physiologically,
      renal 1alpha,25-dihydroxyvitamin D [1,25(OH)(2)D] production is stimulated by PTH
      and phosphate deprivation, and inhibited by 1,25(OH)(2)D itself and calcium. AIM:
      To investigate relations between circulating levels of 1,25(OH)(2)D, 25
      dihydroxyvitamin D (25OHD), PTH, calcium, phosphate, renal function and skeletal
      complications in patients with PHPT. DESIGN: Cross-sectional study. MATERIAL: Two
      hundred and fifty-two consecutive hypercalcaemic Caucasian patients aged 24-91
      (median 65.9) years (85.3% females) with PHPT. RESULTS: In patients with PHPT,
      plasma 1,25(OH)(2)D was increased by 27%[107 (9-250) pmol/l, median (range)]
      compared to controls [84 (18-172) pmol/l, P < 0.001]. In univariate models,
      plasma 1,25(OH)(2)D depended inversely on age (r = -0.23, P < 0.001) and plasma
      phosphate (r = -0.23, P < 0.001) and positively on plasma calcium (r = 0.14, P <
      0.05), plasma 25OHD (r = 0,15, P < 0.05) and creatinine clearance rate (r = 0.32,
      P < 0.001). In the final multiple regression model, plasma 1,25(OH)(2)D depended
      positively on renal function (r(p) = 0.43, P < 0.001) and female sex (r(p) =
      0.15, P < 0.05) but inversely on body mass index (BMI; r(p) = -0.23, P < 0.005)
      and plasma phosphate (r(p) = -0.18, P < 0.05). Plasma 1,25(OH)(2)D correlated
      positively with renal calcium excretion and inversely with lumbar spine bone
      mineral density (BMD) but was not associated with risk of fractures or renal
      stones. CONCLUSION: Patients with PHPT have elevated plasma 1,25(OH)(2)D levels
      but, to a large extent, individual values overlap controls. The increase in
      plasma 1,25(OH)(2)D depends on renal function, hypophosphataemia and the female
      sex and is attenuated by high BMI. High plasma 1,25(OH)(2)D is associated with
      higher plasma calcium levels.

PMID- 17201800
TI  - Effects of evening vs morning thyroxine ingestion on serum thyroid hormone
      profiles in hypothyroid patients.
AB  - OBJECTIVE: Standard drug information resources recommend that l-thyroxine be
      taken half an hour before breakfast on an empty stomach, to prevent interference
      of its intestinal uptake by food or medication. We observed cases in which TSH
      levels improved markedly after changing the administration time of l-thyroxine to
      the late evening. We therefore conducted a pilot-study to investigate whether l
      thyroxine administration at bedtime improves TSH and thyroid hormones, and
      whether the circadian rhythm of TSH remains intact. DESIGN Patients were studied
      on two occasions: on a stable regimen of morning thyroxine administration and two
      months after switching to night-time thyroxine using the same dose. On each
      occasion patients were admitted for 24 h and serial blood samples were obtained.
      PATIENTS: We investigated 12 women treated with l-thyroxine because of primary
      hypothyroidism, who used no medication known to interfere with l-thyroxine
      uptake. MEASUREMENTS: Patients were admitted to hospital and blood samples were
      obtained at hourly intervals for 24 h via an indwelling catheter. Following this
      first hospital admission, all women were asked to switch the administration time
      from morning to bedtime or vice versa. After 2 months they were readmitted for a
      24-h period of hourly blood sampling. Blood samples were analysed for serum TSH
      (immunometric assay), FT4 and T3 (competitive immunoassay), T4 and rT3
      (radioimmunoassay), serum TBG (immunometric assay) and total protein and albumin
      (colourimetric methods). RESULTS: A significant difference in TSH and thyroid
      hormones was found after switching to bedtime administration of l-thyroxine.
      Twenty-four-hour average serum values amounted to (mean +/- SD, morning vs
      bedtime ingestion): TSH, 5.1 +/- 0.9 vs 1.2 +/- 0.3 mU/l (P < 0.01); FT4, 16.7 +/
      1.0 vs 19.3 +/- 0.7 pmol/l (P < 0.01); T3, 1.5 +/- 0.05 vs 1.6 +/- 0.1 nmol/l (P
      < 0.01). There was no significant change in T4, rT3, albumin and TBG serum
      levels, nor in the T3/rT3 ratio. The relative amplitude and time of the nocturnal
      TSH surge remained intact. CONCLUSIONS: l-thyroxine taken at bedtime by patients
      with primary hypothyroidism is associated with higher thyroid hormone
      concentrations and lower TSH concentrations compared to the same l-thyroxine dose
      taken in the morning. At the same time, the circadian TSH rhythm stays intact.
      Our findings are best explained by a better gastrointestinal uptake of l
      thyroxine during the night.

PMID- 17201801
TI  - Short-term fasting-induced autonomic activation and changes in catecholamine
      levels are not mediated by changes in leptin levels in healthy humans.
AB  - OBJECTIVE: In animal models, the adipocyte-secreted hormone leptin increases
      energy expenditure by increasing sympathetic outflow but its role in humans
      remains to be elucidated. We evaluated whether inducing hypoleptinaemia (with and
      without administration of leptin at replacement doses) for 3 days would influence
      catecholamine levels and sympathetic and parasympathetic activity in healthy
      humans. METHODS: We studied six normal-weight subjects in the General Clinical
      Research Center (GCRC) under three conditions: baseline fed state (control study)
      and two 72-h fasting studies (to decrease leptin levels), with administration of
      either placebo or replacement-dose recombinant methionyl human leptin (r
      metHuLeptin) in a randomized, double-blind fashion. In each condition, 24-h
      urinary catecholamine levels, heart rate and heart rate variability (HRV), a
      standard tool for assessing cardiac autonomic modulation, were measured. RESULTS:
      Study parameters remained stable during the control condition and the baseline
      assessment of all three studies. In response to 72-h fasting, which decreased
      serum leptin levels by 80%, 24-h urinary norepinephrine and dopamine levels and
      heart rate increased while cardiac vagal modulation decreased (all P < 0.05).
      Replacement-dose r-metHuLeptin to keep leptin levels within the physiological
      range during fasting did not alter fasting-associated changes in heart rate,
      catecholamine levels or cardiac vagal tone. CONCLUSIONS: The findings of this
      controlled, interventional study indicate that changes in heart rate,
      catecholamine levels and cardiac vagal modulation associated with 72-h fasting
      are independent of regulation by leptin. Thus, changes in leptin levels within
      the physiological range do not seem to play a role in regulating autonomic
      function during short-term starvation in healthy humans.

PMID- 17201802
TI  - Serum thyroglobulin concentrations predict disease-free remission and death in
      differentiated thyroid carcinoma.
AB  - OBJECTIVE: Most studies on the diagnostic value of serum thyroglobulin (Tg)
      concentrations in differentiated thyroid carcinoma (DTC) use fixed cut-off levels
      in heterogeneous groups of patients with respect to initial therapy and do not
      provide prognostic data. The objective was to investigate the prognostic values
      of serum Tg for disease-free remission and death, measured at fixed time-points
      after initial therapy using receiver operator characteristic (ROC) curve
      analyses. DESIGN: Single-centre observational study with 366 consecutive patients
      with DTC, who had all been treated according to the same protocol for initial
      therapy and follow-up. METHODS: Tg concentrations were measured at five fixed
      time-points after initial surgery. Tg cut-off values with the highest accuracy
      were calculated with ROC analyses. RESULTS: During the 8.3 +/- 4.6 years of
      follow-up, 84% of the patients were cured. Pre-ablative Tg levels were an
      independent prognostic indicator for disease-free remission (Tg cut-off value
      27.5 microg/l, positive predictive value 98%). The highest diagnostic accuracies
      of serum Tg for tumour presence were found during TSH-stimulated Tg measurements,
      6 months after initial therapy (Tg cut-off value 10 microg/l; sensitivity 100%,
      specificity 93%). DTC-related mortality was 14%. TSH-stimulated Tg levels before
      ablation and 6 months after initial therapy were independent prognostic
      indicators for death. CONCLUSION: Optimal institutional Tg cut-off levels for
      diagnosis and prognosis should be defined using ROC analyses for each condition
      and time-point. Tg measurements 6 months after initial therapy during TSH
      stimulation had an excellent diagnostic value. Tg levels are independent
      prognostic indicators for disease-free remission and death. Using this strategy,
      high-risk patient groups can be selected based on Tg levels, in addition to
      conventionally used prognostic indicators.

PMID- 17201803
TI  - The transition to menopause reinforces adiponectin production and its
      contribution to improvement of insulin-resistant state.
AB  - OBJECTIVE: To evaluate the influence of menopausal status on the serum
      adiponectin concentration and investigate whether the contribution of adiponectin
      to insulin resistance is modified by menopausal status. SUBJECTS: We conducted a
      population-based, cross-sectional study of 207 premenopausal and 206
      postmenopausal Japanese women. MEASUREMENTS: Data on anthropometric
      characteristics, fasting serum adiponectin, glucose and insulin concentrations
      were used. Insulin resistance (homeostasis model assessment of insulin
      resistance: HOMA-IR) was calculated. RESULTS: Postmenopausal women had
      significantly higher HOMA-IRs than premenopausal women [1.50 (1.42, 1.59) vs 1.18
      (1.12, 1.24), geometric mean (1 standard error range), P = 0.005]. Paradoxically,
      adiponectin levels in postmenopausal women were also significantly higher than
      those in premenopausal women [10.3 (9.95, 10.7) vs 9.04 (8.71, 9.39), P = 0.028].
      Multiple regression analysis showed that body mass index (BMI) was the only
      significantly independent predictor [standardized partial regression coefficients
      (sbeta) = 0.319, P < 0.001] for HOMA-IR among premenopausal women, whereas both
      BMI and adiponectin were the significant predictors among postmenopausal (sbeta =
      0.334 and -0.141, P < 0.001 and < 0.05, respectively). When the subjects were
      restricted to those without metabolic disorders including high blood pressure,
      hypertriglyceridaemia, hypo-HDL cholesterolaemia and high fasting glucose,
      adiponectin (sbeta = -0.249, P < 0.05) was the only significant predictor for
      HOMA-IR among postmenopausal women but BMI was not significant (sbeta = 0.223, P
      = 0.075). CONCLUSIONS: The transition to menopause increases serum adiponectin
      concentrations. And the significant and negative association between adiponectin
      and HOMA-IR was observed only after menopause. Therefore, adiponectin may play a
      role in the improvement of an incipient insulin-resistant state after, rather
      than before, menopause.

PMID- 17201804
TI  - Unmasking of central hypothyroidism following growth hormone replacement in adult
      hypopituitary patients.
AB  - BACKGROUND: The effect of GH replacement on thyroid function in hypopituitary
      patients has hitherto been studied in small groups of children and adults with
      conflicting results. OBJECTIVE: We aimed to define the effect and clinical
      significance of adult GH replacement on thyroid status in a large cohort of GH
      deficient patients. PATIENTS AND METHOD: We studied 243 patients with severe GH
      deficiency due to various hypothalamo-pituitary disorders. Before GH treatment,
      159 patients had treated central hypothyroidism (treated group) while 84 patients
      were considered euthyroid (untreated group). GH dose was titrated over 3 months
      to achieve serum IGF-1 concentration in the upper half of the age-adjusted normal
      range. Serial measurements of serum T4, T3, TSH and quality of life were made at
      baseline and at 3 and 6 months after commencing GH replacement. RESULTS: In the
      untreated group, we observed a significant reduction in serum T4 concentration
      without a significant increase in serum T3 or TSH concentration; 30/84 patients
      (36%) became hypothyroid and needed initiation of T4 therapy. Similar but lesser
      changes were seen in the treated group, 25 of whom (16%) required an increase in
      T4 dose. Patients who became hypothyroid after GH replacement had lower baseline
      serum T4 concentration, were more likely to have multiple pituitary hormone
      deficiencies and showed less improvement in quality of life compared with
      patients who remained euthyroid. CONCLUSION: GH deficiency masks central
      hypothyroidism in a significant proportion of hypopituitary patients and this is
      exposed after GH replacement. We recommend that hypopituitary patients with GH
      deficiency and low normal serum T4 concentration should be considered for T4
      replacement prior to commencement of GH in order to provide a robust baseline
      from which to judge the clinical effects of GH replacement.

PMID- 17201805
TI  - Decreased spinal and femoral neck volumetric bone mineral density (BMD) in men
      with primary osteoporosis and their first-degree male relatives: familial effect
      on BMD in men.
AB  - OBJECTIVE: Low bone mass may be caused by a reduction in the amount of bone or
      density of bone or both. The purpose of this study was to examine differences in
      bone volume and volumetric bone mineral density (vBMD) in men with primary
      osteoporosis and their first-degree male relatives (FDMR). DESIGN: We used dual
      energy X-ray absorptiometry (DXA) to measure areal density, then calculated bone
      volume and volumetric density in 121 men with primary osteoporosis, 73 FDMR and
      66 normal men. We used regression methods adjusting for age, height and weight to
      determine deficits in bone volume and vBMD at the spine and femoral neck between
      men with spinal fractures due to primary osteoporosis, FDMR and normal men.
      RESULTS: Men with osteoporosis had a tendency to smaller bone volume in the spine
      and femoral neck (P = 0.08 and P = 0.09, respectively) and lower volumetric bone
      density at the spine (by about 50%) and femoral neck (by about 30%) compared with
      healthy controls (P < 0.0001). FDMR had no deficit in bone volume but did have
      lower volumetric density at the spine (by 10.2%) compared with healthy controls
      (P < 0.0001). CONCLUSIONS: A deficit in bone mineral accrual may underlie the
      pathogenesis of primary osteoporosis in men, resulting in low vBMD. This is
      likely to be determined by genetic factors, although shared common environmental
      factors may also be important.

PMID- 17201806
TI  - Current prescribing practices and opinions about growth hormone therapy: results
      of a nationwide survey of paediatric endocrinologists.
AB  - BACKGROUND: With the advent of several new treatment indications for recombinant
      hGH, endocrinologists are being asked to make some difficult decisions regarding
      eligibility for treatment. The purpose of this study was to summarize prevailing
      attitudes about GH diagnosis and treatment among paediatric endocrinologists.
      METHODS: We sent surveys to all active US members of the Lawson Wilkins Pediatric
      Endocrine Society (LWPES) listed in the 2004-05 directory (excluding our own
      group of physicians). Thirty-eight per cent of the surveys were returned and 182
      met eligibility for analysis. Surveys were divided into four parts: demographic
      data, answers reflecting current diagnosis practices for GH deficiency and
      treatment with GH, attitudes and clinical practice for the idiopathic short
      stature (ISS) diagnosis, and four case studies. Through a series of questions, we
      elicited the influence towards prescribing GH of current height, growth velocity,
      predicted height, pubertal progression and other variables. Results were entered
      into a Microsoft Access database and statistical evaluation was conducted.
      RESULTS: Eighty-eight per cent of respondents answered 'no' to the statement that
      there is good consensus on who should be treated with GH and over 90% answered
      'no' to the statement that secretagogue testing was the best way to determine if
      a child would benefit from GH. Factors listed by respondents as important for
      prescribing GH include: growth velocity less than the 25th percentile, target
      height less than the 5th percentile and pubertal stage greater than Tanner 2.
      Current height was also important; however, answers varied as to what height
      percentile indicated the need for treatment. When queried about prescribing
      practices for nonstraightforward cases, 62% of respondents answered that the cost
      of GH influenced their decision to treat, 55% responded that concerns of future
      unknown side-effects affected their decision and 37% noted family persistence
      influenced their decision. In response to queries about ISS, 82% answered that
      they were currently using the new indication and 69% answered that there was a
      need for the indication. The statement that short stature could be a disability
      received a 'yes' response from 78%. Answers to the four cases reflected lack of
      consensus, with one-third of all respondents answering that they would treat each
      case, one-third choosing to treat more than two of the cases and one-third
      treating less than two of the cases. CONCLUSION: Endocrinologists differed in
      their answers about cause for treatment with GH but in general favoured use of
      poor growth velocity, poor target height and low IGF-1 levels as indications to
      treat a paediatric patient with GH.

PMID- 17201808
TI  - Effect of long-term orlistat treatment on serum levels of advanced glycation end
      products in women with polycystic ovary syndrome.
AB  - BACKGROUND Women with polycystic ovary syndrome (PCOS) exhibit elevated serum
      advanced glycation end-products (AGE) compared with healthy subjects. Short-term
      administration of orlistat has been shown to reduce the postmeal increase in
      serum AGE levels in women with PCOS and in controls. OBJECTIVE: To evaluate the
      long-term effect of orlistat and a low-calorie diet on serum AGE levels, and on
      the hormonal and metabolic profile of obese PCOS and normal women. DESIGN: A
      clinical trial of 6 months of orlistat administration with an energy-restricted
      diet [basic metabolic rate (BMR) 600 kcal/day] in all subjects. SUBJECTS: Twenty
      nine women with PCOS [aged 27.52 +/- 5.77 years; body mass index (BMI) 35.43 +/-
      5.31 kg/m(2)] and 18 controls (aged 32.06 +/- 5.64 years; BMI 36.39 +/- 6.47
      kg/m(2)). MEASUREMENTS: Serum AGE levels (U/ml), hormonal and metabolic profile.
      RESULTS: PCOS and controls did not differ in BMI (P = 0.58), waist-to-hip ratio
      (WHR) (P = 0.44), fasting insulin concentration (P = 0.45) and glucose-to-insulin
      ratio (GIR) (P = 0.34). PCOS women exhibited statistically higher AGE (P < 0.001)
      and testosterone levels (P < 0.001) compared with controls. After 6 months of
      orlistat treatment, AGE levels showed a statistically significant decrease in
      both groups (PCOS: baseline 9.08 +/- 1.84, post-orlistat 8.56 +/- 1.95, P =
      0.001; controls: baseline 5.02 +/- 0.62, post-orlistat 4.91 +/- 0.69, P = 0.03),
      independently of the BMI reduction in the PCOS group. A significant reduction was
      observed in BMI (PCOS: P < 0.001; controls: P < 0.001), WHR (PCOS: P = 0.002;
      controls: P = 0.04), fasting insulin (PCOS: P < 0.001; controls: P = 0.008), and
      testosterone concentrations in PCOS (P < 0.001). SHBG concentration (PCOS: P =
      0.004; controls: P = 0.008) and GIR (PCOS: P < 0.001; controls: P = 0.03) were
      significantly increased. A significant improvement was also observed in insulin
      resistance indices post-treatment in both groups. CONCLUSIONS: Our data suggest
      that orlistat has a beneficial effect in reducing elevated AGE levels and
      improving the hormonal and metabolic profile in women with PCOS after 6 months of
      treatment, independently of BMI changes.

PMID- 17201807
TI  - Hormonal, pituitary magnetic resonance, LHX4 and HESX1 evaluation in patients
      with hypopituitarism and ectopic posterior pituitary lobe.
AB  - OBJECTIVE: LHX4 and HESX1 are important in early stages of pituitary development
      and their mutations can be associated with an ectopic posterior lobe (EPL) in the
      pituitary of patients with hypopituitarism. The EPL can be located at the median
      eminence or at the path of the pituitary stalk. The aim of this study was to
      analyse LHX4 and HESX1 and characterize the hormonal deficiency profiles,
      establishing relationships with magnetic resonance imaging (MRI) findings in
      these patients. PATIENTS AND DESIGN: Sixty-two patients with hypopituitarism
      associated with EPL were submitted to evaluation of pituitary function, analysis
      of MRI with EPL location and molecular analysis of LHX4 and HESX1 using
      polymerase chain reaction (PCR), digestion with restriction enzyme and automatic
      sequencing. RESULTS: Forty-two patients had a nonvisualized pituitary stalk
      (NPS), and 20 a visualized pituitary stalk (VPS). Most patients (95%) with NPS
      had combined pituitary hormone deficiency (CPHD), with ACTH deficiency in 85%. In
      patients with VPS, CPHD was found in 50% and ACTH deficiency occurred in only
      20%. The frequency of the location of EPL was similar in patients with VPS and
      NPS: 35% at median eminence and 65% at the path of the stalk. No mutations in
      LHX4 and HESX1 were identified. Three new polymorphisms in LHX4 were found.
      CONCLUSIONS: ACTH deficiency is frequent in patients with hypopituitarism and NPS
      (85%), the location of EPL at the median eminence was not predictive of the
      hormonal profile [isolated GH deficiency (IGHD) or CPHD], and LHX4 and HESX1
      genes mutations remain rare causes of hypopituitarism associated with EPL.

PMID- 17201809
TI  - Mutational analyses of WNT7A and HDAC11 as candidate tumour suppressor genes in
      sporadic malignant pancreatic endocrine tumours.
AB  - OBJECTIVE: We and others have reported loss of heterozygosity (LOH) on chromosome
      3p25 in sporadic malignant pancreatic endocrine tumours (PETs). A common region
      of deletion on chromosome 3p25 contains numerous genes, including VHL and
      PPARgamma, that have been excluded previously as candidate tumour suppressor
      genes by DNA sequencing analysis. We have analysed whether WNT7A or HDAC11 was
      biallelically inactivated in a group of well-characterized PETs. PATIENTS AND
      DESIGN: Ten PETs from eight patients were selected from a previous study, where
      LOH on chromosome 3p25 was found in 11 out of 22 sporadic PETs. These tumours
      were examined for inactivating mutations of WNT7A and HDAC11 by direct sequencing
      of all exons and intron-exon boundaries. Inactivation of WNT7A expression by
      aberrant CpG island methylation and WNT7A protein expression were evaluated by
      methylation-specific polymerase chain reaction (PCR) and immunohistochemistry,
      respectively. HDAC11 protein expression was also examined. RESULTS: No point
      mutations, deletion or insertions were detected in either WNT7A or HDAC11 in any
      of the PETs. Two polymorphisms were identified in the third exon of the WNT7A
      gene. CpG methylation of the WNT7A gene was not detected and the WNT7A and HDAC11
      proteins were normally expressed. CONCLUSION: The absence of tumour-specific
      somatic events in WNT7A and HDAC11 suggests that these genes are unlikely to have
      a classical tumour suppressor gene role in sporadic malignant PETs. The putative
      3p25 tumour suppressor remains to be identified.

PMID- 17201810
TI  - Co-expression of ghrelin and its receptor in pancreatic endocrine tumours.
AB  - OBJECTIVE: Expression of ghrelin has been reported in pancreatic endocrine
      tumours, but data on ghrelin receptor protein expression are lacking. The aim of
      this study was to examine the ghrelin receptor, as well as ghrelin, in a selected
      series of these tumours, including multiple endocrine neoplasia 1 (MEN1)
      associated tumours, and to correlate data with clinical features including body
      mass index. DESIGN: Immunohistochemical detection of ghrelin and its receptor was
      performed on frozen tissue from 31 tumours: 9 MEN1 and 22 sporadic. Twenty
      tumours were analysed by quantitative PCR. Plasma ghrelin was assessed in 26
      patients. RESULTS: Twenty-one (68%) of 31 tumours showed immunoreactivity for
      ghrelin (8/9 MEN1) and 19/20 expressed ghrelin mRNA. Ghrelin receptor protein was
      detected in 21/30 (70%) tumours (4/8 MEN1), and mRNA was detected in all analysed
      tumours. Insulinomas had significantly higher levels of receptor mRNA than other
      tumours. Five patients had elevated plasma ghrelin (> 2 SD above the control
      group mean). No significant difference in mean plasma ghrelin levels was found
      between patients (908 +/- 569 ng/l) and controls (952 +/- 164 ng/l). Mean BMI was
      24.3 kg/m(2). There was no association between ghrelin or receptor expression and
      survival. CONCLUSIONS: We report the first immunohistochemical data on expression
      of the ghrelin receptor in pancreatic endocrine tumours: 70% of tumours in our
      material. Concomitant ghrelin and receptor expression was seen in 50% of tumours,
      indicating an autocrine loop. Ghrelin was expressed in 68% of tumours (8/9 MEN1).
      Despite frequent ghrelin expression, elevated circulating ghrelin is rare in
      these patients.

PMID- 17201811
TI  - A diurnal variation in testicular hormone production is maintained following
      gonadotrophin suppression in normal men.
AB  - OBJECTIVE: A diurnal variation in serum testosterone in adult men is well
      recognized, but whether this occurs during exogenous testosterone administration
      and the degree to which it is endogenous to the testis is unclear. DESIGN: A
      clinical research centre investigation of testicular function in normal men.
      PATIENTS: Twenty normal men were recruited, 10 of whom were investigated during
      administration of testosterone with etonogestrel to suppress gonadotrophin
      secretion. MEASUREMENTS: Hourly blood samples were taken over 24 h for
      measurement of testosterone, inhibin B, LH, FSH and cortisol. Urinary excretion
      of testosterone and the testicular steroid epitestosterone was also measured.
      RESULTS: In the controls, a diurnal variation in serum testosterone and LH but
      not FSH was detected. The treated group had similar testosterone concentrations
      but showed no diurnal variation. Periodicity was also detected in inhibin B
      concentrations in 5 of the controls and in 9 of the treated group, who also
      showed synchrony not seen in the controls. Both groups showed diurnal variation
      in cortisol. Urinary testosterone excretion did not show a diurnal variation in
      either group, but this was apparent for epitestosterone with a morning peak in
      both groups despite the markedly lower excretion in the treated men. CONCLUSIONS:
      The diurnal variation of testosterone in normal men is due to a change in
      secretion rather than in clearance and is largely LH driven. An endogenous rhythm
      in both testicular steroidogenesis (epitestosterone) and Sertoli cell function
      (inhibin B) is also present.

PMID- 17201812
TI  - SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis:
      frequency and phenotypic variability.
AB  - OBJECTIVE: The frequency of SHOX mutations in children with idiopathic short
      stature (ISS) has been found to be variable. We analysed the SHOX gene in
      children with ISS and Leri-Weill dyschondrosteosis (LWD) and evaluated the
      phenotypic variability in patients harbouring SHOX mutations. PATIENTS: Sixty
      three ISS, nine LWD children and 21 affected relatives. METHODS: SHOX gene
      deletion was evaluated by fluorescence in situ hybridization (FISH), Southern
      blotting and segregation study of polymorphic marker. Point mutations were
      assessed by direct DNA sequencing. RESULTS: None of the ISS patients presented
      SHOX deletions, but two (3.2%) presented heterozygous point mutations, including
      the novel R147H mutation. However, when ISS patients were selected by sitting
      height : height ratio (SH/H) for age > 2 SD, mutation frequency detection
      increased to 22%. Eight (89%) LWD patients had SHOX deletions, but none had point
      mutations. Analysis of the other relatives in the families carrying SHOX
      mutations identified 14 children and 17 adult patients. A broad phenotypic
      variability was observed in all families regarding short stature severity and
      Madelung deformities. However, the presence of disproportional height, assessed
      by SH/H, was observed in all children and 82% of adult patients, being the most
      common feature in our patients with SHOX mutations. CONCLUSION: Patients with
      SHOX mutations present a broad phenotypic variability. SHOX mutations are very
      frequent in LWD (89%), in opposition to ISS (3.2%) in our cohort. The use of SH/H
      SDS as a selection criterion increases the frequency of SHOX mutation detection
      to 22% and should be used for selecting ISS children to undergo SHOX mutation
      molecular studies.

PMID- 17201813
TI  - The role of desmopressin in bilateral and simultaneous inferior petrosal sinus
      sampling for differential diagnosis of ACTH-dependent Cushing's syndrome.
AB  - OBJECTIVE: Bilateral inferior petrosal sinus sampling (BIPSS) with corticotrophin
      releasing hormone (CRH) stimulation is currently the gold standard test for the
      differential diagnosis of ACTH-dependent Cushing's syndrome. Reports on the use
      of desmopressin in this approach are limited. The aim of this study was to
      evaluate the use of desmopressin during BIPSS in a cohort of patients with ACTH
      dependent Cushing's syndrome. DESIGN: A retrospective case-record study.
      PATIENTS: Fifty-six patients with confirmed ACTH-dependent Cushing's syndrome
      underwent BIPSS with desmopressin stimulation when presenting negative pituitary
      tumour imaging. MEASUREMENTS: Central to peripheral (CEN:PER) ACTH gradient,
      lateralization of the ACTH source and surgical tumour confirmation were
      evaluated. RESULTS: A CEN:PER ACTH gradient was found in 40 patients under basal
      conditions (CEN:PER >or= 2) and in 47 patients after desmopressin stimulation
      (CEN:PER >or= 3). Ectopic ACTH-producing tumours (three lung carcinoid tumour,
      one thymus carcinoid tumour and one thymus hyperplasia) were confirmed in five
      out of nine patients without the CEN:PER ACTH gradient, and four cases were false
      negative for Cushing's disease. Lateralization (IPS:IPS >or= 1.4) was observed in
      80.8% of patients under basal conditions (38/47) and in 97.8% after desmopressin
      (46/47), and it was surgically confirmed in 78.7%. There were no false-positive
      cases. Sensitivity and specificity were 92.1% and 100%, respectively.
      CONCLUSIONS: Desmopressin improves the differential diagnosis of ACTH-dependent
      Cushing's syndrome by amplifying the CEN:PER and IPS:IPS ACTH gradients, and is
      therefore a useful ACTH secretagogue in BIPSS.

PMID- 17201814
TI  - Ghrelin does not regulate the GH response to insulin-induced hypoglycaemia in
      children but could be involved in the regulation of cortisol secretion.
AB  - OBJECTIVE: Ghrelin activates the growth hormone secretagogue receptor GHS-R. It
      strongly stimulates GH secretion and has a role in energy homeostasis. The
      relationship between plasma ghrelin and cortisol levels during insulin-induced
      hypoglycaemia in prepubertal and pubertal children has not yet been investigated.
      The aim of the present study was to establish whether insulin-induced
      hypoglycaemia stimulates ghrelin secretion and whether changes in ghrelin
      concentrations are related to changes in GH and cortisol in children. DESIGN AND
      PATIENTS: We studied a group of 20 children and adolescents (five girls, 15 boys,
      mean age 10.8 +/- 3.7 years) undergoing insulin tolerance tests (ITTs) for
      clinical investigation of GH deficiency. MEASUREMENTS: Stimulation tests were
      performed to investigate the relationship between ghrelin, GH, cortisol and
      glucose levels according to age and pubertal stage by determining the ghrelin
      profiles during insulin-induced hypoglycaemia (at 0, 60 and 120 min). RESULTS:
      Ghrelin was significantly and inversely related to body weight, height, body mass
      index (BMI) and age of children (P < 0.05). Significant changes in ghrelin levels
      (P = 0.00013) were found after the insulin bolus, with a decline at 60 min and an
      increase to baseline values at 120 min. Changes in cortisol levels were
      negatively correlated with changes in ghrelin at 60 min (r = -0.59, P = 0.004)
      and at 120 min (r = -0.605, P = 0.003). CONCLUSIONS: This study shows that
      ghrelin might not regulate the GH response to insulin-induced hypoglycaemia in
      prepubertal and pubertal children. A role for ghrelin in the regulation of
      cortisol secretion can be hypothesized concerning the negative correlation
      between changes in ghrelin and cortisol. Furthermore, the results imply that
      ghrelin secretion is age dependent and is a function of growth.

PMID- 17201815
TI  - Hypercalcaemia in a patient with a gastrointestinal stromal tumour.

PMID- 17201816
TI  - Unusual late development of dopamine agonist resistance in two women with
      hyperprolactinaemia associated with transition from micro to macroadenoma.

PMID- 17201817
TI  - Metastatic prolactinoma presenting as a cervical spinal cord tumour in multiple
      endocrine neoplasia type one (MEN-1).

PMID- 17201818
TI  - Impaired cardiopulmonary parameters in young women with polycystic ovary
      syndrome.

PMID- 17201822
TI  - Factors influencing the short-term outcome following thoracic surgery in 98 dogs.
AB  - OBJECTIVES: To evaluate the factors influencing the short-term (<14 days) outcome
      of thoracic surgery in dogs. METHODS: A retrospective review of 98 dogs
      undergoing thoracotomy over a five-year period was undertaken. RESULTS: A pre
      operative diagnosis was achieved in 69 per cent of cases. Intrathoraic neoplasia
      had the lowest pre-operative diagnosis rate (5.5 per cent). Mortality rates of 21
      per cent were recorded and were significantly higher for intrathoracic neoplasia
      (50 per cent) and significantly lower for persistent ductus arteriosus (7.4 per
      cent) and vascular ring anomaly (0 per cent). Median sternotomy was the preferred
      approach for pyothorax (85 per cent) and penetrating thoracic injuries (66 per
      cent). Intercostal thoracotomy was the preferred approach for all other diseases.
      Postoperative complications occurred in 39 per cent of cases. Wound complications
      were more common for pyothorax (45 per cent) and following median sternotomy (71
      per cent). Thoracic drains were placed in 77 per cent of cases and complications
      were recorded in 23 per cent. Pyothorax and chylothorax had thoracic drains
      maintained for significantly longer periods of time. Longer thoracic drain
      duration was correlated significantly with increased complication rates. CLINICAL
      SIGNIFICANCE: The short-term outcome following thoracic surgery is influenced by
      diagnosis. The thoracic approach is determined by intrathoracic disease, but may
      influence outcome by affecting the incidence of postoperative wound
      complications. The risk of thoracic drain complications increases with drain
      duration, which is influenced by the underlying disease. Drains should be
      maintained for the minimal amount of time possible.

PMID- 17201823
TI  - Thoracic bite trauma in dogs: a comparison of clinical and radiological
      parameters with surgical results.
AB  - OBJECTIVES: Canine bite wounds may cause severe underlying tissue trauma even
      with no clinically evident puncture wounds. In order to assess the ability of pre
      operative diagnostic parameters to predict the extent of internal damage
      inflicted by a thoracic bite wound, the clinical, radiological and surgical data
      of 45 dogs that sustained thoracic bite trauma were recorded. METHODS: Clinical,
      radiographic and surgical parameters from 45 dogs of various breeds with thoracic
      bite trauma, were analysed (P<0.05). All dogs were treated according to a
      previously described protocol and had exploratory surgery including a
      thoracotomy. RESULTS: Mainly small-breed dogs were traumatised. Clinical and
      radiological data were suggestive of internal trauma but not reliable as accurate
      indicators for internal lesions. Only radiological evidence of lung contusion was
      significantly associated with the presence of surgically confirmed lung contusion
      (P=0.006). Dogs with postoperative wound complications had a significantly higher
      risk of dying than those without complications (P=0.04). CLINICAL SIGNIFICANCE:
      This study concludes that according to protocol an optimal management of thoracic
      bite wounds in small dogs includes surgical exploration of the wound and the
      thoracic cavity in the presence of flail or pseudo-flail chest, fractured ribs,
      radiological evidence of lung contusion, pneumothorax or any combination of
      these.

PMID- 17201821
TI  - Use of biochemical markers of osteoarthritis to investigate the potential disease
      modifying effect of tibial plateau levelling osteotomy.
AB  - OBJECTIVES: To evaluate the hypothesis that the concentration of the 1/20/5D4
      epitope of keratan sulphate, cartilage oligomeric matrix protein and total
      sulphated glycosaminoglycans in synovial fluids from dogs with cranial cruciate
      ligament disease would be affected by tibial plateau levelling osteotomy. In
      addition, to evaluate the hypothesis that medial meniscal release or meniscal
      injury would alter the expression of these candidate biomarkers. METHODS: Forty
      one dogs with naturally occurring cranial cruciate ligament disease were
      recruited prospectively. Synovial fluids were collected from the index joint
      before surgery and six weeks and six months postsurgery. Following tibial plateau
      levelling osteotomy, synovial fluids were assayed for 1/20/5D4 epitope of keratan
      sulphate and cartilage oligomeric matrix protein concentration using an
      inhibition ELISA and for sulphated glycosaminoglycans using a direct dye-binding
      assay. RESULTS: The sulphated glycosaminoglycans ratio did not change
      significantly during the study. Medial meniscal injury at entry was associated
      with lower concentrations of synovial fluid cartilage oligomeric matrix protein
      (P<0.05, unpaired t test). There was no association between medial meniscal
      release and the changes in marker concentrations, either from 0 to six weeks or 0
      to six months. CLINICAL SIGNIFICANCE: Tibial plateau levelling osteotomy did not
      significantly alter the expression of the named candidate biomarkers. These
      findings reflect the limited nature of the arthrotomy or indicate that tibial
      plateau levelling osteotomy does not influence the progression of osteoarthritis
      (OA). From these studies, there is no evidence that tibial plateau levelling
      osteotomy affects cartilage metabolism.

PMID- 17201824
TI  - Comparison of three techniques for the diagnosis of urinary tract infections in
      dogs with urolithiasis.
AB  - OBJECTIVES: To identify an appropriate sampling technique(s) to accurately detect
      the bacteria causing urinary tract infections in dogs with urolithiasis. METHODS:
      Twenty-one dogs with urolithiasis were included in the study. Three types of
      samples were taken from each dog. Urine was collected by cystocentesis, and a
      urinary bladder mucosal biopsy and urolith were retrieved during cystotomy. The
      samples were then cultured on blood agar and MacConkey's agar to identify the
      bacteria associated with urinary tract infections. RESULTS: Bacterial urinary
      tract infection was found in 16 cases (76.19 per cent). The most prevalent
      bacteria found to cause urinary tract infection were Escherichia coli (n=7),
      followed by coagulase-positive Staphylococcus species (n=4), Klebsiella
      pneumoniae (n=2), Pseudomonas aeruginosa (n=2) and Proteus mirabilis (n=1). In
      the case of a positive urine culture, the same bacteria were also cultured from
      the urinary bladder mucosal biopsy alone or from both the urinary bladder mucosal
      biopsy and urolith. However, in the case of a negative urine culture, bacteria
      were found to be present in the urinary bladder mucosal biopsy or urolith
      cultures in 23.81 per cent of dogs. The uroliths that gave positive culture
      results were either infection-induced uroliths composed of struvite and calcium
      carbonate phosphate, ammonium acid urate only or metabolic uroliths composed of
      calcium oxalate and calcium phosphate, or calcium phosphate only. All the
      uroliths that gave negative culture results were metabolic uroliths composed of
      calcium oxalate and/or calcium phosphate, and uric acid and calcium phosphate.
      CLINICAL SIGNIFICANCE: When the culture from the urine obtained by cystocentesis
      is negative, cultures of urinary bladder mucosal biopsy and urolith are
      recommended in dogs with urolithiasis in order to accurately assess the
      microbiological status of the urinary tract.

PMID- 17201825
TI  - Bilothorax following cholecystectomy in a dog.
AB  - A 10-year-old, entire female Pyrenean shepherd dog was presented for acute onset
      of gastroenteritis. An abdominal ultrasound examination showed the presence of a
      suspected gall bladder mucocele. After surgery for cholecystectomy, the dog
      showed signs of an acute onset of respiratory distress due to bilothorax. The
      bilothorax responded well to medical treatment that comprised of thoracocentesis
      and oral steroids.

PMID- 17201826
TI  - Traumatic bilateral ureteric rupture in two dogs.
AB  - Two cases of bilateral ureteric rupture in dogs are reported. Both dogs were
      presented following road traffic accidents with signs of depression and abdominal
      distension. Both animals were azotaemic and abdominal fluid analysis was
      consistent with uroabdomen. In case 1, the injuries affected the proximal portion
      of both ureters and the dog was euthanased. In case 2, the ruptures were located
      more distally and a ureteroneocystostomy was performed, with contralateral
      ureteronephrectomy. This dog is clinically normal 16 months postoperatively.

PMID- 17201827
TI  - Two cases of dysuria as a complication of single-session bilateral triple pelvic
      osteotomy.
AB  - Dysuria is a rare, but nevertheless severe postoperative complication associated
      with single-session bilateral triple pelvic osteotomy. Two cases are described in
      which contrast radiography of the lower urinary tract was used to diagnose
      urethral compression due to pelvic canal narrowing. Relief of the pressure on the
      urethra was achieved with an external fixation device, which distracted the
      acetabular fragments of the pelvis. In both cases the dysuria was resolved. The
      significance of this complication and its possible causes, especially regarding
      surgical technique, are discussed.

PMID- 17201828
TI  - Vaginoperitoneal fistula after ovariohysterectomy in three bitches.
AB  - Vaginoperitoneal fistulation was detected in three neutered bitches undergoing
      retrograde positive contrast vaginourethrography. This is a rarely detected
      complication of ovariohysterectomy and appears to result in no clinical signs.

PMID- 17201829
TI  - Infection of a total hip prosthesis in a dog caused by Achromobacter(Alcaligenes)
      xylosoxidans.
AB  - A four-year-old male, neutered Labrador retriever was presented with progressive
      left hindlimb lameness 10 months following total hip replacement. Radiography
      revealed changes consistent with infection and culture of joint fluid from the
      left coxofemoral joint revealed Achromobacter (Alcaligenes) xylosoxidans. The
      prosthesis was removed. Culture of the acetabular cup confirmed Achromobacter
      xylosoxidans. Achromobacter xylosoxidans is an uncommon but serious cause of
      nosocomial epidemics in hospitals for human beings. To the authors' knowledge,
      this is the first report of total hip prosthetic infection with Achromobacter
      xylosoxidans. Little is reported about its pathogenicity in human beings and the
      authors failed to retrieve any reports of its clinical significance in animals.

PMID- 17201830
TI  - Rectovaginal fistula following colectomy with an end-to-end anastomosis stapler
      for a colorectal adenocarcinoma.
AB  - An 11-year-old, female neutered Labrador retriever was presented with a micro
      invasive differentiated papillar adenocarcinoma at the colorectal junction. A
      colorectal end-to-end anastomosis stapler device was used to perform resection
      and anastomosis using a transanal technique. A rectovaginal fistula was diagnosed
      two days later. An exploratory laparotomy was conducted and the fistula was
      identified and closed. Early dehiscence of the colon was also suspected and
      another colorectal anastomosis was performed using a manual technique. Comparison
      to a conventional manual technique of intestinal surgery showed that the use of
      an automatic staple device was quicker and easier. To the authors' knowledge,
      this is the first report of a rectovaginal fistula occurring after end-to-end
      anastomosis stapler colorectal resection-anastomosis in the dog. To minimise the
      risk of this potential complication associated with the limited surgical
      visibility, adequate tissue retraction and inspection of the anastomosis site are
      essential.

PMID- 17201831
TI  - Tracheal necrosis following tracheal intubation in a dog.
AB  - Tracheal rupture and stenosis are well-reported problems in human beings and cats
      following endotracheal intubation. However, this problem has been rarely reported
      in dogs. This case report describes a case of tracheal necrosis 5 days following
      endotracheal intubation in a dog associated with overinflation of the
      endotracheal tube cuff and multiple changes in position.

PMID- 17201832
TI  - What is your diagnosis? Symmetrical lupoid onychodystrophy.

PMID- 17201837
TI  - ICD Implantation in infants and small children: the extracardiac technique.
AB  - BACKGROUND: There is no clear methodology for implantation of an internal
      cardioverter-defibrillator (ICD) in infants and small children. The aim of this
      study was to assess efficacy and safety of an extracardiac ICD implantation
      technique in pediatric patients. PATIENTS AND METHODS: An extracardiac ICD system
      was implanted in eight patients (age: 0.3-8 years; body weight: 4-29 kg). Under
      fluoroscopic guidance a defibrillator lead was tunneled subcutaneously starting
      from the anterior axillar line along the course of the 6th rib until almost
      reaching the vertebral column. After a partial inferior sternotomy, bipolar
      steroid-eluting sensing and pacing leads were sutured to the atrial wall (n = 2)
      and to the anterior wall of the right ventricle (n = 8). The ICD device was
      implanted as "active can" in the upper abdomen. Sensing, pacing, and
      defibrillation thresholds (DFTs) as well as impedances were verified
      intraoperatively and 3 months later, respectively. RESULTS: In seven of eight
      patients, intraoperative DFT between subcutaneous lead and device was <15 J. In
      the eighth patient ICD implantation was technically not feasible due to a DFT >20
      J. During follow-up (mean 14.5 months) appropriate and effective ICD discharges
      were noted in two patients. DFT remained stable after 3 months in four of six
      patients retested. A revision was required in one patient due to lead migration
      and in another patient due to a lead break. CONCLUSIONS: In infants and small
      children, extracardiac ICD implantation was technically feasible. Experience and
      follow-up are still limited. The course of the DFT is unknown, facing further
      growth of the patients.

PMID- 17201838
TI  - Validation of criteria for selective his bundle and para-hisian permanent pacing.
AB  - BACKGROUND: His Bundle (HB) pacing is a valid alternative to right ventricular
      pacing for patients with preserved His-ventricle conduction who are candidates
      for permanent stimulation. Permanent pacing in the HB area enables Selective HB
      pacing (SHBP) or para-Hisian pacing (PHP) to be achieved. The aim of our study
      was to draw up a set of easy criteria to differentiate and validate the two kinds
      of stimulations according to the pacing output and the ECG/EKG signals. METHODS
      AND RESULTS: From February to July 2005, 17 patients eligible for a pacemaker
      (PM) procedure underwent implantation with the Medtronic SelectSecure lead
      (Medtronic, Minneapolis, MN, USA) screwed into the HB area.SHBP was defined when
      the intrinsic QRS was equal, in both duration and morphology, to the paced QRS,
      the His-Ventricular (H-V) interval was equal to Pace-Ventricular interval (Vp-V)
      and, at low output, only the HB was captured, while increasing the output
      resulted in both the HB and right ventricular (RV) being captured (widening of
      QRS at high output). Conversely, PHP was defined when the intrinsic QRS differed
      from the paced one, either in morphology or in duration and, at high output, both
      the RV and HB were captured (non-SHBP), while decreasing the output resulted in
      losing HB capture (widening of QRS at low output). According to these criteria,
      SHBP was achieved in 11 patients, while in the remaining 6, PHP was obtained. No
      adverse events were reported. CONCLUSIONS: The above criteria enabled SHBP and
      PHP to be validated easily and clearly. A longer follow-up will be needed in
      order to ascertain whether the clinical outcome of these two approaches differs.

PMID- 17201839
TI  - Intrathoracic far-field electrocardiogram allows continuous monitoring of
      ischemia after total coronary occlusion.
AB  - INTRODUCTION: Recording of intrathoracic far-field electrocardiograms (FF-ECG)
      via can and electrodes of implantable cardioverter-defibrillators (ICD) is a
      promising method for continuous monitoring of myocardial ischemia. We assessed
      the hypothesis that experimentally induced ischemia provokes segment changes in
      the FF-ECG that can be detected by the ICD. METHODS AND RESULTS: In seven pigs
      with an ICD implanted in the left pectoral region and electrodes placed in the
      right ventricle and the superior vena cava, we occluded all major coronary
      arteries in proximal and distal locations for 180 s each. Surface and FF-ECGs
      were compared for presence and time course of ischemic ST segment changes.
      Reliable detection of ischemia by ST segment analysis was possible in all (38/38)
      experiments. Maximum deviation from baseline was larger in FF-ECG (1.21 mV) than
      surface ECG leads (0.23 mV, P < 0.01) for all occlusion sites. Ischemia could be
      detected earlier (P < 0.05) in the FF-ECG, with a sensitivity of 100%, 93%, and
      100% after occlusions in the left anterior descending, left circumflex, and right
      coronary arteries, respectively. CONCLUSION: Intrathoracic FF-ECG allows reliable
      and reproducible detection of experimentally induced ischemia originating from
      all major coronary arteries and therefore could be an interesting tool for
      clinicians in monitoring high risk patients.

PMID- 17201840
TI  - Perioperative biventricular pacing leads to improvement of hemodynamics in
      patients with reduced left-ventricular function--interim results.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been introduced as a new
      therapeutic modality in patients with chronic heart failure. However, most
      studies have investigated the hemodynamic effects in congestive, but not
      postoperative heart failure. OBJECTIVE: The following study investigates
      hemodynamic effects of perioperative temporary biventricular pacing in patients
      undergoing open heart surgery. In 54 patients one left and one right ventricular
      epicardial wire was placed during open heart operations. Hemodynamic parameters
      were measured immediately after the operation and 6 as well as 24 hours
      postoperatively. Transesophageal echocardiography was performed 1 hour
      postoperatively. RESULTS: Of the 54 patients (59.2%), 32 responded to
      biventricular pacing with an increase in cardiac output; in these patients
      synchronized ventricular contraction could be verified echocardiographically.
      This hemodynamic benefit persisted 6 hours and 24 hours postoperatively. The
      remaining 22 patients did not show any hemodynamic improvement from biventricular
      stimulation. CONCLUSION: Biventricular pacing leads to significant rise in
      cardiac output in approximately 59% of patients with severely reduced left
      ventricular function and widened QRS complexes. Further studies are necessary to
      define clearly the clinical characteristics of patients who show remodeling by
      CRT.

PMID- 17201841
TI  - Pacemaker-induced superior vena cava syndrome: clinical evaluation of long-term
      follow-up.
AB  - BACKGROUND: Pacemaker-induced superior vena cava (SVC) syndrome is a rare but
      serious complication of permanent pacemaker implantation. Because of its rarity,
      little is known about the long-term prognoses of such patients. METHODS: Five
      patients, mean age 62 +/- 11.4 years, with pacemaker-induced SVC syndrome for
      more than 10 years were investigated. The clinical evaluation included: exercise
      testing, thrombophilia lab tests, and a chest CT. RESULTS: Two of the patients
      manifested complications of SVC syndrome which included thoracoabdominal
      subcutaneous collaterals. One of these patients simultaneously developed an
      increase in the pacing threshold which required the implantation of epicardial
      leads. Three of the five patients had normal age-adjusted VO(2) AT und VO(2) max.
      Four of the patients were both heterozygous for a polymorphism of PAI-1 and were
      homozygous for a polymorphism of t-PA. One of these patients also was
      heterozygous for a polymorphism of factor V and glycoprotein IIb/IIIa. The chest
      CTs revealed extensive and varying collateral circulation patterns in all of the
      patients. CONCLUSIONS: The development of pacemaker-induced SVC syndrome is the
      result of various predisposing factors including thrombophilia. Many patients
      retain normal age-adjusted cardiopulmonary capacity and demonstrate stable
      clinical findings on the long-term as the result of the development of extensive
      collateral vessel systems. The most serious complication was the combination of
      SVC syndrome and the simultaneous malfunctioning of one of the leads requiring
      implantation of a new lead.

PMID- 17201842
TI  - Laser assistance for extraction of chronically implanted endocardial leads:
      infectious versus noninfectious indications.
AB  - BACKGROUND: Powered sheaths, including Excimer laser sheaths, were introduced for
      the removal of transvenous pacing and defibrillator leads. The purpose of this
      study was to develop an algorithm to better predict which patients are likely to
      benefit from these devices. METHODS: We reviewed 283 consecutive patients in whom
      a total of 500 leads (302 pacing and 198 defibrillator leads) were extracted over
      a 5-year period at our operative facilities. Laser assist was utilized whenever
      moderate traction failed. RESULTS: In 128 patients, 203 leads were removed for
      noninfectious indication. In 155 patients, 297 leads for infectious indications,
      including sepsis 22% (111), pocket infection 23% (115), and erosion 14% (71).
      Laser assistance was required for 6%+/- 5% (+/- 95% confidence interval) of
      septic leads, 51%+/- 7% of leads associated with erosion or pocket infection and
      60%+/- 7% of noninfected leads (P = 0.001). Laser assistance was necessary more
      often for leads implanted >12 months (53%+/- 5%) than 12 months or less (6%+/-
      5%) (P = 0.001) and for ventricular (52%+/- 6%) compared to atrial (35%+/- 7%)
      leads (P = 0.001). CONCLUSIONS: Chronically implanted leads (>12 months),
      especially noninfected leads and leads associated with erosion or pocket
      infection, should be referred for extraction with powered sheaths to ensure
      successful removal. However, leads that are associated with systemic sepsis can
      generally be removed without powered sheaths.

PMID- 17201843
TI  - Magnetocardiography study on ventricular depolarization-current pattern in
      patients with brugada syndrome and complete right-bundle branch blocks.
AB  - BACKGROUND: The objective of this study is to use magnetocardiography to
      determine the existence of a small abnormal current during ventricular
      depolarization in patients with Brugada syndrome. To understand this small
      difference in abnormal current during ventricular depolarization, we compared
      abnormal currents of patients with cases of complete right-bundle-branch block
      (CRBBB). METHODS AND RESULTS: We developed a whole-heart electrical bull's eye
      map (WHEBEM) that uses magnetocardiograms (MCGs) to visualize the current
      distribution in a circular map. MCGs of Brugada syndrome patients (n = 16), CRBBB
      patients (n = 10), and controls (n = 12) at rest were recorded. In the WHEBEMs of
      Brugada syndrome patients, the magnitude of the S-wave current in the upper-right
      direction of the anterior side is larger than that of the controls. In addition,
      the R-wave current direction is similar to that of the controls, and the R-wave
      vector is distributed over a larger area than that of the controls. On the other
      hand, the CRBBB patients have a distribution of R-wave currents over a larger
      area in the left anteromedian region and the left posteromedian region. Moreover,
      in all CRBBB patients, S-wave currents with a large magnitude have the same
      direction distributed over a small area. CONCLUSIONS: The WHEBEM findings suggest
      that there is an abnormal current in the direction to the upper right (in the S
      wave) in the anterosuperior region of Brugada syndrome patients. We thus conclude
      that a WHEBEM has the potential to detect characteristics of heart disease.

PMID- 17201844
TI  - Convective cooling effect on cooled-tip catheter compared to large-tip catheter
      radiofrequency ablation.
AB  - BACKGROUND: Both actively cooled-tip and large-tip catheters are currently
      available clinically to create large endomyocardial lesions during application of
      radiofrequency (RF) energy. The purpose of this study was to compare the effect
      of convective cooling at physiologic flow rates on RF lesion size using both
      actively cooled and large-tip catheters. METHODS: Porcine hearts were sectioned
      into 72 pieces and placed in a temperature-controlled saline bath (37 degrees C)
      with varying directed flow rates (0, 1, 2, and 3 L/min). Cooled-tip RF ablation
      (4 mm tip) was performed for 1 minute on 36 tissue sections with power manually
      titrated to keep tip temperature below 40 degrees C. Large-tip catheter ablation
      (10 mm tip) was performed at 65 degrees C target temperature for 1 minute on 36
      tissue sections. For each catheter, flow rates were randomized between
      applications. The tissue pieces were sectioned and measured to determine lesion
      depth, width, and volume. RESULTS: Lesion dimensions were independent of the flow
      rate for the cooled-tip catheter (mean volumes: 382.0 +/- 121.6, 419.9 +/- 133.4,
      375.9 +/- 169.1, and 346.7 +/- 173.4 mm(3) for 0, 1, 2, and 3 L/min flow rate,
      respectively, P = 0.78). For the large-tip catheter, lesion size varied
      significantly with flow, such that higher flow rates produced larger lesions
      (mean volumes: 120.7 +/- 50.7, 256.5 +/- 97.9, 393.4 +/- 149.9, and 548.9 +/-
      157.0 mm(3) for 0, 1, 2, and 3 L/min flow rate respectively, P < 0.001)
      CONCLUSION: During RF ablation, blood flow rate significantly affects lesion size
      for large-tip but not cooled-tip catheters. At low flow rates (0-1 L/min) cooled
      tip catheters create larger lesions, while at high flow rates (3 L/min) large-tip
      catheters create larger lesions.

PMID- 17201845
TI  - Randomized study of propofol effect on electrophysiological properties of the
      atrioventricular node in patients with nodal reentrant tachycardia.
AB  - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is probably the
      most common form of paroxysmal supraventricular tachycardia. Percutaneous
      catheter ablation is a technique to interrupt cardiac conduction pathways
      selectively. The anesthetist is challenged to provide a safe anesthetic which
      takes into account the electrophysiologist's requirements for minimal cardiac
      conduction interference. Propofol is an ideal drug. However, previous studies
      have shown that the infusion of propofol has sometimes been associated with
      bradyarrhythmias or conversion of arrhythmias to sinusal rhythm. The purpose of
      this report is to verify the interferences of propofol in the
      electrophysiological properties of the atrioventricular (AV) node conduction
      system in patients with AVNRT. METHODS: Patients were randomly assigned to
      receive either a placebo or propofol at sedative doses. An electrophysiological
      study was performed consisting of measuring the anterograde (AERPFP) and
      retrograde effective refractory period of the fast (RERPFP) and the anterograde
      effective refractory period of the slow (AERPSP) AV nodal pathway. Reciprocating
      tachycardia was induced and the cycle length (CL) and atrial-His (AH), His
      ventricular (HV), and ventriculoatrial (VA) intervals were measured. RESULTS:
      Propofol did not cause alteration (P > 0.05) in the AERPFP or RERPFP and the
      AERPSP AV nodal pathway. The AH, HV, and VA intervals were not affected.
      Sustained reciprocating tachycardia could be induced in the all patients. All
      slow pathways were successfully identified and ablated. CONCLUSION: Propofol has
      no effect on the electrophysiological properties of the AV node conduction
      system. It is thus a suitable anesthetic agent for use in patients undergoing
      ablative procedures.

PMID- 17201846
TI  - Low energy biphasic waveform cardioversion of atrial arrhythmias in pediatric
      patients and young adults.
AB  - BACKGROUND: Low-dose biphasic waveform cardioversion has been used for the
      termination of atrial arrhythmias in adult patients. The energy required for
      termination of atrial arrhythmias in pediatric patients is not known. The
      objective of this study is to determine the minimum energy required for
      successful external cardioversion of atrial arrhythmias in pediatric patients
      using biphasic waveform current. METHODS: Prospective study of all patients less
      than 24 years of age with and without congenital heart disease undergoing
      synchronized cardioversion for atrial arrhythmias. Patients were assigned to
      receive an initial biphasic energy shock of 0.2-0.5 J/kg and if unsuccessful in
      terminating the arrhythmia, subsequent sequential shocks of 1 and 2 J/kg would be
      administered until cardioversion was achieved. The end point of the cardioversion
      protocol was successful cardioversion or delivery of three shocks. RESULTS:
      Between June 2005 and June 2006, 16 patients underwent biphasic cardioversion for
      atrial flutter or fibrillation. The mean age was 14.7 +/- 6.4 years (range: 2
      weeks to 24 years). The mean weight was 51 +/- 21 kg (range: 3.8-82 kg). Seven
      patients had normal cardiac anatomy, three had a single ventricle (Fontan), two
      had a Senning operation; the remaining four patients had varied forms of
      congenital heart disease. The median length of time that the patients were in
      tachycardia was 12 hours (range: 5 minutes to 2 months). Using either
      transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE),
      no thrombi were identified in any patient. All patients were successfully
      cardioverted with biphasic waveform energy. The successful energy shock was 0.35
      +/- 0.19 J/kg (range: 0.2-0.9 J/kg). All but one patient were successfully
      cardioverted with less than 0.5 J/kg. The transthoracic impedance range was
      between 41 and 144 Omega; one patient had an impedance of 506 Omega (2-week-old
      infant with a weight of 3.8 kg). The mean current delivered was 5.4 +/- 2.2 A
      (range: 1-11 A). CONCLUSION: Low-dose energy using biphasic waveform shocks can
      be used for successful termination of atrial arrhythmias in pediatric patients
      with and without congenital heart disease.

PMID- 17201847
TI  - Acute and chronic effects of extensive radiofrequency lesions in the canine caval
      veins: implications for ablation of atrial arrhythmias.
AB  - BACKGROUND: Although radiofrequency (RF) ablation within the caval veins has been
      increasingly used to treat a variety of atrial tachyarrhythmias, the consequences
      of RF ablation in the caval veins are unknown. We explored the acute and chronic
      angiographic and pathological effects of extensive RF ablation in the caval
      veins. METHODS: Under fluoroscopy guidance, conventional (4 mm tip, 60 degrees C,
      60 seconds) RF applications (n = 6-7) were delivered in each vena cava (from +/-2
      cm into the vein to the veno-atrial junction) of 15 dogs (10 +/- 3 kg). Animals
      were killed 1 hour and 5 weeks after ablation for histological analysis.
      Angiography was performed before ablation (acute dogs only) and at sacrifice to
      assess the degree of vascular stenosis. RESULTS: In acute dogs (n = 5), luminal
      narrowing was noted in 10/10 (100%) targeted veins (mild in two; moderate in
      three and severe in five, including two total occlusions). In the six chronic
      animals that completed the protocol (four died during follow-up), stenosis was
      also observed in 12/12 (100%) ablated veins (mild in six; moderate in four and
      severe in two). Of these, one superior vena cava was suboccluded with development
      of extensive collateral circulation. Histologically, acute lesions displayed
      typical transmural coagulative necrosis, whereas chronic lesions revealed intimal
      proliferation, necrotic muscle replaced with collagen, endovascular contraction,
      and disruption and thickening of the internal elastic lamina. CONCLUSION: In this
      model, extensive RF ablation in the caval veins may result in significant
      vascular stenosis. These findings may have implications for catheter ablation of
      arrhythmias originating within the caval veins.

PMID- 17201848
TI  - Significance and utility of plasma brain natriuretic peptide concentrations in
      patients with idiopathic ventricular arrhythmias.
AB  - BACKGROUND: Secretion of B-type natriuretic peptide (BNP) appears to be regulated
      mainly by wall tension, and an increase in the plasma BNP concentration is
      considered to reflect ventricular structural and functional abnormalities. The
      aim of this study was to clarify the significance and utility of the measurement
      of the plasma BNP in the setting of idiopathic ventricular arrhythmias (I
      VT/PVCs). METHODS: This study included 135 patients with symptomatic, monomorphic
      I-VT/PVCs (73 women; 53 +/- 17 years; 50 ventricular tachycardias [VTs], 85
      premature ventricular contractions) who underwent radiofrequency catheter
      ablation. None had structural heart disease or renal dysfunction. RESULTS: The
      plasma BNP concentration exceeded the normal range (>18.4 pg/mL; high BNP
      concentration) in 79 patients (56%). The high BNP concentration was found more
      often in I-VT/PVCs originating from the left ventricle (LV; 74%) than the right
      ventricle (RV; 49%; P < 0.01). The plasma BNP concentration correlated with the
      age (P = 0.0001) and frequency of premature ventricular contractions (P <
      0.0001), and left-sided I-VT/PVCs and the presence of controlled hypertension
      were independent predictors of a high BNP concentration (both P < 0.05). In
      patients with a successful ablation and high BNP concentration before the
      ablation, the BNP concentration decreased to the normal range in 61% of patients
      after ablation. In patients with a failed ablation, the BNP concentration did not
      decrease to the normal range after ablation in any of the patients (P < 0.0005).
      CONCLUSIONS: The plasma BNP concentration was elevated in about 60% of the
      patients with symptomatic I-VT/PVCs. Normalization of the high BNP concentration
      after ablation may indicate a successful ablation.

PMID- 17201849
TI  - Group purchasing organizations: optimizing cardiac device selection, therapy
      delivery, and fiscal responsibility.
AB  - Group purchasing organizations (GPOs) have played a major role in supporting
      health care delivery in recent years as the healthcare industry has faced
      stronger economic pressures. Consequently, a position statement was drafted to
      act as a guideline for a GPO in creating a fiscally responsible, yet unrestricted
      environment for physicians to select the most appropriate cardiac device for
      their patients. This cardiac device selection guideline is to be implemented in
      hundreds of member hospitals but may be of use in non-member hospitals as well.
      The guideline will only be effective when the physicians or cardiac device
      caregivers have the knowledge and skills to optimally program and match device
      therapies and algorithms to individual patient needs.

PMID- 17201850
TI  - A lamb in wolff's clothing.
AB  - A symptomatic woman with an electrocardiogram (ECG)-based diagnosis of Wolff
      Parkinson-White (WPW) syndrome underwent electrophysiologic studies that revealed
      a likely fasciculo-ventricular tract.

PMID- 17201851
TI  - Inappropriate shock: a failure of SVT discriminators in a dual chamber ICD?
AB  - Inappropriate shock remains a major issue in patients with implantable
      cardioverter defibrillators. We examine an inappropriate shock delivered in a
      patient with atrial tachycardia that conducted 1:1. We reconstruct the device
      algorithms that led to therapy delivery and discuss programming changes that
      could be considered.

PMID- 17201852
TI  - Optimization of device programming for cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy may lead to remarkable improvement in clinical
      status in selected patients with heart failure. However, approximately 20-30% of
      patients may not respond to this treatment. One of the reasons for this may be
      suboptimal programming of the device, which has particular considerations as
      compared to standard pacemakers. Hemodynamic response to pacing may be affected
      by timing of the atrioventricular (AV) interval, affecting synchronicity of
      atrial and ventricular contraction. In addition current biventricular devices
      have separate right and left ventricular channels that allow programming of an
      interventricular (VV) interval with right or left ventricular preexcitation. This
      article focuses on the parameters that may be optimized for biventricular pacing,
      and reviews the different techniques currently available for this application,
      with special emphasis paid to echocardiography.

PMID- 17201853
TI  - Using computers to improve the psychosocial care of implantable cardioverter
      defibrillator recipients.
AB  - Person-to-person psychosocial interventions (e.g., psychological, social) enhance
      the well-being of implantable cardioverter defibrillator (ICD) patients.
      Computerized care, though, represents an opportunity to further capitalize on
      techniques that have already been deemed effective. This includes the provision
      of tailored, effective patient education; reducing device-specific anxiety; and
      enhancing social support networks. The aim of this paper is to identify the ways
      in which computerized psychosocial care could potentially enhance the well-being
      of ICD recipients. For example, computers may be particularly adept at providing
      patient education due to the ease in which content can be adapted to meet patient
      needs. Further, evidenced-based treatments for anxiety and depression (e.g.,
      cognitive behavioral therapy) have demonstrated good applicability to
      computerized formats. Social support can also be provided online in the form of
      bulletin boards, email list-servs, or structured online support groups. Despite
      the existence of some limitations, the use of computers in affecting psychosocial
      outcomes in implantable defibrillator recipients warrants greater attention.

PMID- 17201854
TI  - Latent atriofascicular pathway participating in a wide complex tachycardia:
      differentiation from ventricular tachycardia.
AB  - Accessory pathways with anterograde decremental conduction properties usually are
      characterized by presence of antegrade preexcitation during atrial pacing. We
      report a 38-year-old man with frequent episodes of palpitation. No evidence of
      ventricular preexcitation was seen during sinus rhythm or atrial pacing. All
      electrophysiologic maneuvers were compatible with an antidromic tachycardia using
      atriofascicular pathway as the antegrade limb and the atrioventricular nodal
      pathway as retrograde limb. Radiofrequency ablation at recording site of
      accessory pathway potential resulted in cure of tachycardia with no recurrence
      during 3-month follow-up. This report indicated that atriofascicular pathway
      mediated tachycardia should be considered in differential diagnosis of all cases
      of wide complex tachycardia with left bundle branch morphology and left axis.

PMID- 17201855
TI  - Bundle brunch reentrant ventricular tachycardia with two distinct conduction
      patterns in a patient with complete right bundle branch block.
AB  - We report a rare case of bundle branch reentrant ventricular tachycardia [BBRVT].
      A 67-year-old female was admitted for management of wide QRS tachycardia (right
      bundle branch block [RBBB] and a southwest axis). The mapping procedure revealed
      the tachycardia circuit consisted of the left anterior fascicle (LAF) as an
      antegrade, and the right bundle as a retrograde pathway. She presented RBBB
      during sinus rhythm. LAF ablation changed the tachycardia configuration to a
      northwest axis and prolonged the cycle length. Left posterior fascicle ablation
      terminated the tachycardia, and complete atrioventricular block occurred, which
      showed the unidirectional conduction over the right bundle.

PMID- 17201856
TI  - Cardiac magnetic resonance and cardiac magnetic field mapping in a patient with
      stress-induced cardiomyopathy (tako-tsubo).
AB  - We encountered a 65-year-old woman with typical electrocardiogram (ECG) changes
      and new-onset left ventricular dysfunction with apical ballooning that exhibited
      typical changes of tako-tsubo-like cardiomyopathy. We used cardiac magnetic
      resonance (CMR) and cardiac magnetic field mapping (CMFM) to detect changes in
      structural, mechanical, and electrophysiological myocardial properties during
      follow-up. CMR displayed an acute myocardial injury, but neither fibrosis nor
      necrosis. CMFM exhibited severely disturbed repolarization with an inhomogeneous
      magnetic field. These pathological findings persisted much longer than the
      abnormalities detected by CMR and the ECG.

PMID- 17201857
TI  - Multiple premature beats triggered ventricular arrhythmias during pilsicainide
      infusion in a patient with inferior ST-segment elevation.
AB  - A 17-year-old man was referred to our hospital for treatment of common paroxysmal
      atrial flutter. His electrocardiogram at rest showed subtle ST-segment elevation
      in leads II, III, and aV(F). Intravenous pilsicainide caused further ST-segment
      elevation in the inferior leads, new ST-segment depression in leads V2-V6, two
      distinct forms of premature ventricular complexes (PVCs) triggering short runs of
      polymorphic ventricular tachycardia (VT). An infusion of isoproterenol suppressed
      these arrhythmias and normalized the ST-segment. Pilsicainide may induce PVCs and
      polymorphic VT in atypical Brugada syndrome.

PMID- 17201858
TI  - Successful use of a transvenous dual-chamber automatic implantable cardiac
      defibrillator after a classic Fontan operation for tricuspid atresia.
AB  - We report the first successful totally percutaneous pacing and defibrillation of
      a single ventricle in a 52-year-old woman who had undergone a classic Fontan
      operation (atriopulmonary connection) for tricuspid atresia 21 years earlier.
      Left ventricular pacing and sensing was obtained with a bipolar lead in the
      lateral cardiac vein, and defibrillation was obtained with a coronary sinus coil
      lead and an "active can" in the retromammary position to optimize the current
      vector. This approach has significant potential benefits because it avoids a
      repeat thoracotomy, with its associated mortality and morbidity.

PMID- 17201859
TI  - Discordant regulation of CRP and NT-proBNP plasma levels after electrical
      cardioversion of persistent atrial fibrillation.

PMID- 17201860
TI  - Negative symptoms of schizophrenia: a problem that will not go away.
AB  - OBJECTIVE: Negative symptoms of schizophrenia are a common, enduring, and
      debilitating component of the psychopathology of schizophrenia. Although efforts
      thus far to elucidate a distinct schizophrenia subtype based upon negative
      symptoms have yielded mixed results, there are nevertheless neurobiological
      correlates of the negative symptom typology. METHOD: A review of nosology,
      typology, and assessment tools for determining core negative symptoms in
      schizophrenia. RESULTS: Negative symptoms can be difficult to evaluate
      objectively. Current rating scales 'capture' key domains of negative symptoms, in
      spite of considerable overlap between these domains. However, each objective
      assessment trades off methodological rigor and detail against brevity of
      assessment and ease of use. CONCLUSION: The description of new methods for
      measuring these devastating symptoms, coupled with the ongoing development of
      novel antipsychotics and agents that augment antipsychotics have fuelled renewed
      interest in the evaluation of negative symptoms and optimism that better
      treatments for negative symptoms can be found.

PMID- 17201861
TI  - Acute bipolar mania: a systematic review and meta-analysis of co-therapy vs.
      monotherapy.
AB  - INTRODUCTION: The aim of this meta-analysis was to systematically review the
      effectiveness of co-therapy compared with monotherapy for people with bipolar
      mania. METHOD: MEDLINE, Embase, Psychinfo, The Cochrane Library and reference
      lists of retrieved studies were searched without language restrictions for
      randomized controlled trials evaluating co-therapy compared with monotherapy for
      acute bipolar mania. Each trial was assessed for susceptibility to bias. Data on
      mania outcomes, withdrawals, extrapyramidal symptoms and weight were extracted
      and pooled effect estimates summarized as relative risks (RR) or differences in
      mean values (MD) where appropriate. RESULTS: Eight eligible studies were included
      (1124 participants). Significant reductions in mania (Young Mania Rating Scale,
      YMRS) scores were shown for haloperidol, olanzapine, risperidone and quetiapine
      as co-therapy compared with monotherapy with a mood stabilizer. For atypical
      antipsychotics combined, the pooled difference in mean scores was 4.41 (95% CI:
      2.74, 6.07). Significantly more participants on co-therapy met the response
      criterion (at least 50% reduction in YMRS score), RR 1.53 (1.31, 1.80). With some
      drugs, co-therapy decreased tolerability compared with monotherapy, and resulted
      in greater weight gain. There were insufficient data to compare one co-therapy
      regimen with another. CONCLUSION: The addition of antipsychotic treatment to
      established mood-stabilizer treatment is more effective than mood-stabilizer
      treatment alone.

PMID- 17201862
TI  - Perceived parental rearing of bipolar offspring.
AB  - OBJECTIVE: To explore the impact of growing up with a parent with a bipolar
      disorder. First, we compared parental rearing behavior perceived by young adult
      offspring of bipolar parents with parental rearing behavior perceived by same
      aged young adults from the general population. Secondly, we examined the
      associations between perceived parental rearing behavior and parental
      psychopathology and psychopathology in offspring. METHOD: Subjects were 129
      offspring of 80 bipolar parents and their spouses and 1122 young adults from the
      general population. In offspring the Structured Clinical Interview for DSM-IV was
      used to assess DSM-IV diagnoses and the EMBU was used to assess perceived
      parental rearing in both groups. RESULTS: In general, offspring growing up in a
      family with a bipolar parent perceived their mothers as less rejecting, more
      emotionally warm and less overprotecting and their fathers as less emotionally
      warm and less overprotecting compared with young adults from the general
      population. Perceived rejection was related to psychopathology in offspring.
      CONCLUSION: Overall, parental rearing in families with a parent with a bipolar
      disorder is not more dysfunctional, as perceived by their offspring, than in
      families from the general population. Offspring with a bipolar disorder perceive
      their parents as more rejecting.

PMID- 17201863
TI  - Is psychosis in DSM-IV mania due to severity? The relevance of selected
      demographic and comorbid social-phobic features.
AB  - OBJECTIVE: We tested whether factors other than episode severity contributed to
      psychosis in mania. METHOD: Psychiatrists collected systematic clinical data on
      1090 hospitalized DSM-IV manic patients in France, and completed the Mania Rating
      Scale (MRS) and the Scale for the Assessment of Positive Symptoms (SAPS).
      RESULTS: Using DSM-IV specifiers, 21.9% were non-severe, 28.2% severe without
      psychosis, and 49.9% severe with psychosis. On the MRS, patients with psychosis
      scored significantly higher (P < 0.0001) than non-severe, but did not differ from
      the severe without psychosis. We found significant correlations between both the
      Hallucination and the Delusion subscores of the SAPS and the MRS, as well as
      correlations between age, single marital status, comorbid social phobia and
      psychotic mania. CONCLUSION: Apart from episode severity, social isolation -
      associated with younger age, single marital status and social phobia - seems to
      make a contribution to the origin of manic psychosis largely independent from
      such severity.

PMID- 17201864
TI  - Altered omega-3 polyunsaturated fatty acid status in depressed post-myocardial
      infarction patients.
AB  - OBJECTIVE: Lower levels of long-chain omega-3 polyunsaturated fatty acids (n-3
      LCPUFAs) and increased inflammation have been associated with both depressive
      disorder and myocardial infarction (MI). The present study investigated whether
      patients who develop depression post-MI, have higher arachidonic
      acid/eicosapentanoic acid (AA/EPA) ratios than non-depressed post-MI patients and
      whether depressed post-MI patients have signs of increased inflammation as
      measured by C-reactive protein (CRP). METHOD: Serum AA/EPA ratio and plasma CRP
      levels were quantified in 50 post-MI patients, of which 29 were depressed and 21
      non-depressed. RESULTS: Compared with the non-depressed group, depressed post-MI
      patients had significantly higher AA/EPA ratios. No significant difference was
      observed in CRP levels. CONCLUSION: Depressed post-MI patients had lower levels
      of n-3 LCPUFAs as measured by mean AA/EPA ratio and no signs of increased
      inflammation as determined by CRP levels.

PMID- 17201865
TI  - Impulsiveness in obsessive-compulsive disorder: results from a family study.
AB  - OBJECTIVE: Although obsessive-compulsive disorder (OCD) is usually conceptualized
      as an anxiety disorder some studies suggested it to be a deficit of impulse
      control. The purpose of this study was to assess impulsiveness in OCD families
      and compare it to control families. METHOD: Seventy cases and their 139 relatives
      were compared with 70 controls and their 134 relatives from a German family study
      on OCD (German Epidemiologic Network for OCD Studies). All subjects were
      interviewed and diagnosed according DSM-IV criteria and were administered the
      Barratt Impulsiveness Scale (BIS) and PADUA-Inventory to assess obsessive
      compulsive symptoms. RESULTS: OCD subjects had significantly higher scores of
      cognitive impulsiveness. However, first-degree relatives of OCD cases and of
      controls had comparable BIS-11 scores. Significant associations of aggressive
      obsessions and checking with cognitive impulsiveness were found. CONCLUSION: OCD
      is a severe mental disorder that is characterized by a lack of cognitive
      inhibition. However, impulsiveness does not represent a familial trait in
      families of OCD subjects.

PMID- 17201866
TI  - Parent-teacher disagreement regarding psychopathology in children: a risk factor
      for adverse outcome?
AB  - OBJECTIVE: To investigate if parent-teacher discrepancies in reports of
      behavioral/emotional problems in children predict poor outcome. METHOD: A total
      of 1154 4- to 12-year-old children from the general population were followed up.
      At the first assessment, parent and teacher ratings were obtained with the Child
      Behavior Checklist (CBCL) and Teacher's Report Form (TRF). Fourteen years later,
      DSM-IV diagnoses were assessed, and ratings of self-reported and parent-rated
      behavioral and emotional problems were obtained. RESULTS: CBCL and TRF scores
      predicted most of the outcomes, but in general, discrepancies between CBCL and
      TRF scores did not. There were some exceptions. For instance, higher parental vs.
      teacher ratings of aggressive behaviors increased the risk of suicide
      attempts/self-mutilation. CONCLUSION: Risk factors for self-mutilating behaviors
      may be supplemented with parent-reported aggressive behaviors that are not
      observed by the teachers. In general, whereas CBCL and TRF scale scores were
      useful predictors of outcome, parent-teacher discrepancies were not.

PMID- 17201867
TI  - Comorbid personality disorder and treatment use in a community sample of youths:
      a 20-year follow-up.
AB  - OBJECTIVE: The impact of comorbid personality disorder (PD) on subsequent
      treatment and psychotropic drug use was examined in a representative sample of
      over 700 individuals. METHOD: Axis I disorders and PD were assessed by self- and
      mother-report at mean ages 13 and 22 years, and by self-report at mean age 33.
      Mothers reported treatment use by participants before mean age 33; participants
      reported treatment and psychotropic drug use at mean age 33. RESULTS: Individuals
      with multiple axis I disorders without PD, axis I disorder-PD comorbidity, and
      single disorders were compared simultaneously to individuals not diagnosed.
      Overall, odds of subsequent and past year treatment or psychotropic drug use or
      both were highest when PD co-occurred with a mood, an anxiety, a disruptive, or a
      substance use disorder. CONCLUSION: Co-occurring personality pathology may
      contribute to elevated mental health service use, including use of psychotropic
      drugs, among young adults in the community.

PMID- 17201868
TI  - Violence from young women involuntarily admitted for severe drug abuse.
AB  - OBJECTIVE: To simultaneously evaluate actuarial and dynamic predictors of severe
      in-patient violence among women involuntarily admitted for severe drug abuse.
      METHOD: All patients admitted to special facilities for involuntary treatment of
      absconding-prone, previously violent, drug abusing women in Sweden were assessed
      with the Staff Observation Aggression Scale, revised. Actuarial data on risk
      factors for violence were collected and considered in an extended Cox
      proportional hazards model with multiple events and daily assessments of the
      Broset Violence Checklist as time-dependent covariates. RESULTS: Low-grade
      violence and being influenced by illicit drugs were the best predictors of severe
      violence within 24 h. Significant differences in risk for violence between
      different institutions were also found. CONCLUSION: In-patient violence risk is
      rapidly varying over time with being influenced by illicit drugs and exhibiting
      low-grade violence being significant dynamic predictors. Differences in violence
      between patients could not be explained by patient characteristics.

PMID- 17201869
TI  - Is the dementia rate increasing in Beijing? Prevalence and incidence of dementia
      10 years later in an urban elderly population.
AB  - OBJECTIVE: To examine the time trend of dementia morbidity over the past decade
      in Beijing, China. METHOD: In 1997, 1593 community-dwelling elderly aged 60+
      years were examined and followed-up over 2-years to identify incident dementia. A
      similar cohort study of dementia conducted in the same district 10 years prior
      was used as historical comparison to examine the time trend of dementia
      incidence. RESULTS: Forty prevalent dementia cases were identified at the initial
      examination for a prevalence of 2.51% (95% CI: 1.74-3.28) and 25 incident cases
      were identified at the follow-up visit for an incidence of 0.90% (0.55-1.25)
      among residents aged 60+ years. Alzheimer's dementia (AD) was the most common
      type of dementia in both prevalent and incident cases. CONCLUSION: The prevalence
      and incidence rates of dementia in Beijing were slightly higher than those 10
      years ago, which was partly because of population aging. AD became the most
      common subtype of dementia.

PMID- 17201870
TI  - Do your patients suffer from excessive yawning?
AB  - OBJECTIVE: Yawning has been described in relation to drugs such as serotonin
      reuptake inhibitors, levodopa, dopamine agonists, MAO B inhibitor, morphine,
      methadone, buprenorphine, dextromethorphan, benzodiazepine, lidocaine, and
      flecaine. This is a report of two patients, on long-term escitalopram therapy
      (more than 8 weeks) with stable dosing, who presented excessive yawning.
      Escitalopram is widely used in major depressive disorder and generalized anxiety
      disorder. METHOD: A clinical description of two cases. RESULTS: Two females (62
      and 59 years old, respectively) developed excessive daytime yawning. It was not
      associated with sedation or a feeling of needing sleep. The dosage was reduced
      and yawning disappeared some hours later. The patients' depression did not recur.
      CONCLUSION: Yawning has been described in relation to different selective
      serotonin reuptake inhibitors and remitted following their discontinuation; it is
      interesting that the reported yawning in these two cases disappeared with the
      reduction of dosage, rather than the interruption of treatment.

PMID- 17201871
TI  - Attention to side effects enhances medical adherence.

PMID- 17201872
TI  - The changing face of non-variceal, upper gastrointestinal hemorrhage.

PMID- 17201873
TI  - Irritable bowel syndrome in the 21st century: perspectives from Asia or South
      east Asia.
AB  - Asian irritable bowel syndrome (IBS) studies not only confirm the truth of this
      functional disorder but also describe the current disease situation of this
      continent, with its variable socioeconomic backgrounds. Most Asian community IBS
      prevalence is within 5-10%, regardless of gender or ethnic character. As well as
      meeting the main Rome II criteria, Asian IBS subjects also have many minor
      symptoms. Thus this recommendation remains useful to diagnose Asian IBS. Also,
      female patients commonly express constipation-predominant (C-) symptoms. Extra
      colonic symptoms are common in Asia, for example dyspepsia, insomnia and
      irritable urinary bladder. Asian IBS subjects do experience psychological
      disturbances including anxiety, depression, agoraphobia and neuroticism.
      Accordingly, their quality of life is poor and there is absenteeism leading to
      excessive physician visits. Abnormal gut motor and sensory functions have been
      indicated among the Asian IBS subjects. Now, there is evidence of altered colonic
      neuroimmune function leading to gut hypersensitivity and dysmotility. An Asia
      Pacific trial also confirmed tegaserod efficacy on female C-IBS subjects. More
      than 90% of nurses have very limited IBS knowledge, and are unable even to
      explain it clearly. In conclusion, Western recommended criteria clearly diagnose
      Asian IBS and many factors are mutual leading to IBS. Current IBS treatments
      remain useful but additional reeducation for medical professionals appears to be
      needed.

PMID- 17201874
TI  - Silent myocardial ischemia in coronary artery disease patients under aspirin
      therapy presenting with upper gastrointestinal hemorrhage.
AB  - AIM: To identify the risk factors for myocardial ischemia in patients undergoing
      aspirin therapy for coronary artery disease (CAD) presenting with upper
      gastrointestinal hemorrhage and to ascertain the impacts on mortality and length
      of hospital stay. METHODS: Adults with CAD under aspirin therapy (100 mg once
      daily) presenting to the emergency department with upper gastrointestinal
      hemorrhage were retrospectively recruited and divided into group A (ischemia) and
      group B (non-ischemia). Charts were reviewed for various demographic, laboratory
      and outcome data. Electrocardiograms were interpreted blindly by a senior
      cardiologist. RESULTS: A total of 152 patients, 72.4% men and 27.6% women, were
      analyzed. Of these, 31 patients had ischemia and were placed in group A and 121
      patients did not have ischemia and were in group B. Independent multivariate
      predictors of myocardial ischemia were history of triple vessel disease (odds
      ratio [OR], 9.24; 95% confidence interval [CI], 2.00-42.72), lower diastolic
      blood pressure (OR, 1.09; 95% CI, 1.02-1.16), lower hematocrit (OR, 1.41; 95% CI,
      1.16-1.70), and higher blood urea nitrogen (OR, 0.94; 95% CI, 0.89-0.98).
      Patients with myocardial ischemia had significantly longer hospital length of
      stay (8.7 +/- 4.0 days vs 5.4 +/- 1.7 days; P < 0.001) and higher in-hospital
      mortality (16.1%vs 2.5%; P < 0.01) than did those without myocardial ischemia.
      CONCLUSION: Myocardial ischemia is a relatively common complication in CAD
      patients under aspirin therapy presenting with upper gastrointestinal hemorrhage.
      A history of CAD with triple vessel disease, higher blood urea nitrogen, lower
      diastolic blood pressure and lower hematocrit may help identify patients who are
      at increased risk of myocardial ischemia, which tends to be associated with
      higher in-hospital mortality and increased length of hospital stay.

PMID- 17201875
TI  - Cardiac involvement in Crohn's disease: echocardiographic study.
AB  - BACKGROUND: Crohn's Disease (CD) commonly presents extra-intestinal
      manifestations, but cardiac involvement is considered rare. The aim of the
      present study was to assess cardiac involvement in CD and its possible
      correlation with activity, duration, localization and therapy. PATIENTS AND
      METHODS: A group of 68 patients with CD and a control group of 60 healthy
      subjects were subjected to a transthoracic echocardiogram with Doppler study.
      RESULTS: The study found overall morphologic alterations in 47/68 CD patients
      (69.11%) versus 12/60 controls (20.0%; P < 0.01); mitral valve prolapse in 20/68
      CD patients (29.4%) versus 4/60 controls (6.6%; P < 0.01); and pericardial
      effusion in 13/68 CD patients (19.1%)versus 1/60 controls (1.6%; P < 0.01). The
      following findings were frequent, but without statistical significance: mitral
      insufficiency, 9/68 CD (13.2%) versus 3/60 controls (5.0%); tricuspidalic
      insufficiency, 8/68 CD (11.7%) versus 3/60 controls (5%); aortic insufficiency,
      3/68 CD (4.4%) versus none in the control group; and decreased left ventricle
      ejection fraction, 5/68 CD (7.3%) versus none in the control group. Pericardial
      effusion was found to be related to CD activity (r = 0.375; P = 0.002) as well as
      decreased ejection fraction (r = 0.358; P = 0.003). No correlation with age, sex,
      duration, therapy or localization of disease was found. CONCLUSIONS: These
      findings suggest that CD frequently determines cardiac involvement, although it
      is usually subclinical. The alteration of cytokine network, especially the
      elevated levels of tumor necrosis factor-alpha, could be implicated in the
      cardiac alterations because it was observed, as for raised oxidative stress, in
      other heart diseases.

PMID- 17201876
TI  - Gastric tube cancer: immunohistochemical study of 10 lesions in six patients.
AB  - BACKGROUND AND AIM: Gastric tube cancer (GTC), defined as carcinoma arising in
      the reconstructed gastric tube after esophagectomy, has been increasingly
      reported, but its pathogenesis remains unclear. Therefore, the aim of this study
      was to examine clinically and pathologically 10 GTCs in six patients. METHODS: In
      addition to examination of the clinicopathological features of GTCs, the adjacent
      gastric tube mucosa was also evaluated immunohistochemically using gastric
      foveolar markers (MUC5AC and human gastric mucin), pyloric gland markers (MUC6
      and M-GGMC-1), and intestinal markers (MUC2 and CD10). RESULTS: All patients were
      men and three patients had multiple GTCs. All GTCs were located on the middle to
      lower portion of the gastric tube. Nine GTCs had tubular and/or papillary
      adenocarcinoma components, and another was signet-ring cell carcinoma. Intestinal
      metaplasia was found in non-neoplastic mucosa adjacent to nine GTCs. Metaplastic
      goblet cells adjacent to five GTCs expressed both gastric and intestinal markers,
      which were similar to the corresponding GTC cells, indicating a close association
      between the GTCs and metaplastic goblet cells. The other three GTCs expressed
      only intestinal markers, which may support the suggestion that the intestinal
      phenotype is expressed later in cancerous development. CONCLUSION: Pathogenesis
      of GTCs could be identical to that of ordinary gastric cancer. Cancerous
      multiplicity associated with esophageal cancer may also play a role in the
      development of GTCs.

PMID- 17201877
TI  - Relationship between molecular markers and endoscopic findings in laterally
      spreading tumors.
AB  - BACKGROUND AND AIM: Characteristic clinicopathological features of laterally
      spreading tumors (LSTs) have been reported by endoscopists; however, only a few
      studies have been conducted on the biological features. These studies were not
      fully associated with the endoscopic findings of LSTs. The aim of this study was
      to estimate the biological features of each type of endoscopic finding of LST
      using two molecular markers, matrix metalloproteinase-7 (MMP-7) and beta-catenin.
      METHODS: Expression of the molecular markers and the endoscopic findings were
      compared in 22 LSTs and 14 subpedunculated polyps. MMP-7 and beta-catenin were
      immunostained. Three types of representative endoscopic findings of LST were
      defined as segments in LSTs. They were 15 granular segments, seven large nodular
      segments, and seven flat segments that corresponded to the area composed of
      aggregates of similar size granules, large nodules of diameter more than 10 mm,
      and a flat surface with no granule, respectively. RESULTS: Expression of MMP-7
      and coexpression of MMP-7 and beta-catenin were higher in large nodular segments
      than in granular segments (P < 0.0167). Among the three types of segments, flat
      segments showed the highest expression densities of beta-catenin accumulated in
      the nucleus. Large nodular segments and subpedunculated polyps showed similar
      expression patterns for the molecular markers. CONCLUSIONS: This study provides
      new and important information on the relationship between the molecular markers
      and endoscopic findings of LSTs.

PMID- 17201878
TI  - Increase of mast cells may be associated with infiltration of eosinophils and
      proliferation of microvessels in gastric eosinophilic granuloma.
AB  - BACKGROUND: Gastric eosinophilic granuloma (GEG) is a rare disease. Recently this
      disease has begun to increase in China. In the present study, the function and
      the role of mast cells (MC) in the pathogenesis of GEG were investigated.
      METHODS: Paraffin-embedded tissue sections from 23 GEG patients and 15 gastric
      ulcer (GU) patients, were stained with antihuman mast cell tryptase for counting
      the MC and degranulated MC. Antihuman CD34 antibody was used for detecting the
      microvessel density (MVD) with immunohistochemical technique. Mast cell
      degranulation was also studied using electron microscopy. RESULTS: The quantity
      of both MC and degranulated MC were higher in both GEG and GU than in normal
      gastric mucosa. The proportion of degranulated MC was higher in the GEG but in GU
      it was similar to normal mucosa. The MVD was higher in both GU and GEG than that
      in the normal gastric mucosa and it was higher in the high-MC group than in the
      low-MC group in GEG. The positive correlation between eosinophil and MC was
      present only in GEG, not in GU. CONCLUSIONS: The infiltration of eosinophils and
      MVD may be associated with the increase of MC in GEG. This suggests that in
      addition to eosinophils, MC might be the important cells in the pathogenesis of
      GEG.

PMID- 17201879
TI  - Effect of oral esomeprazole on recurrent bleeding after endoscopic treatment of
      bleeding peptic ulcers.
AB  - BACKGROUND: After endoscopic treatment of bleeding peptic ulcer, a high-dose
      infusion of omeprazole substantially reduces the risk of recurrent bleeding. The
      role of oral proton pump inhibitors for these patients is uncertain. The purpose
      of the present study was to assess whether the use of oral esomeprazole would
      reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding
      peptic ulcers. METHODS: Patients with actively bleeding ulcers or ulcers with non
      bleeding visible vessels were treated with an epinephrine injection followed by
      thermocoagulation. After hemostasis had been achieved, they were randomly
      assigned in a double-blind fashion to receive esomeprazole (40 mg p.o. twice
      daily for 3 days) or placebo. The outcome measures studied were recurrent
      bleeding, blood transfusion requirement, surgery and death. RESULTS: A total of
      70 patients were enrolled, 35 in each group. Bleeding recurred within 30 days in
      two patients (5.7%) in the esomeprazole group, as compared with three (8.6%) in
      the placebo group (P = 0.999). Blood transfusion requirement was 2.8 +/- 1.4
      units in the esomeprazole group and 2.7 +/- 1.3 units in the placebo group (P =
      0.761). Duration of hospitalization was 4.82 +/- 1.8 days in the esomeprazole
      group and 4.58 +/- 2.7 days in the placebo group (P = 0.792). No patients needed
      surgery for control of bleeding and no patients died in both groups. CONCLUSIONS:
      After successful endoscopic treatment of bleeding peptic ulcer, oral use of
      esomeprazole might offer no additional benefit on the risk of recurrent bleeding.

PMID- 17201880
TI  - Transabdominal gastroesophageal devascularization without transection for
      bleeding varices: results and indicators of prognosis.
AB  - BACKGROUND: Esophagogastric devascularization is an operation that can be
      performed for endoscopically uncontrolled variceal bleeding in hospitals having
      only basic surgical instruments and is therefore an appropriate procedure for
      small hospitals in developing countries. The aim of this study was to analyze one
      hospital's experience of this operation in consecutive patients with variceal
      bleeding. METHODS: Between 1996 and 2003, 45 patients (30 male, 15 female) who
      had a mean age of 40 years (range 7-78 years) underwent devascularization
      procedures. Of the 45, 23 had cirrhosis and 22 had non-cirrhotic portal
      hypertension (11 extrahepatic portal venous obstruction, 11 non-cirrhotic portal
      fibrosis), and 18 patients had emergency procedures and 27 were elective.
      Mortality, morbidity, rebleeding rates and the prognostic factors for death were
      assessed. RESULTS: Elective and emergency mortality was one (3.7%) and 11 (61%)
      patients, respectively. There was no rebleeding in hospital. At follow up (mean
      48 months, range 3-92 months) overall survival in patients with cirrhosis was 7
      out of 20 and in patients with non-cirrhotic portal hypertension was 19 of 21.
      Five (17%) had recurrent variceal hemorrhage, of whom three, all cirrhotic
      patients, died. Preoperative prognostic indicators for death were emergency
      surgery, a Child-Pugh score >or=10, preoperative blood transfusion >or=20 units
      and renal failure. CONCLUSIONS: Gastroesophageal devascularization effectively
      controls variceal bleeding especially in non-cirrhotic patients with portal
      hypertension. In the elective situation it carries a low mortality and rebleed
      rate. In emergencies the prognosis is poor with advanced cirrhosis, following
      large quantities of blood transfusion and deranged renal function. It is
      suggested that this operation be offered especially to non-cirrhotic patients in
      hospitals in developing countries where facilities for more sophisticated
      procedures are not available.

PMID- 17201881
TI  - Different effects of polymorphisms of tumor necrosis factor-alpha and interleukin
      1 beta on development of peptic ulcer and gastric cancer.
AB  - BACKGROUND AND AIM: In Western countries, polymorphism of pro-inflammatory
      cytokine genes is associated with the development of gastric cancer and duodenal
      ulcer. The aim of this study was to clarify the association of polymorphisms of
      interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha with susceptibility
      to peptic ulcer diseases and gastric cancer in Japan. METHODS: The IL-1beta-511/
      31 and TNF-alpha-308/-857/-863/-1031 genotypes were determined in Helicobacter
      pylori-positive patients with gastritis only (n = 164), gastric ulcers (n = 110),
      duodenal ulcers (n = 94), or gastric cancers (n = 105), and in H. pylori-negative
      controls (n = 172). RESULTS: Carriage of the alleles TNF-alpha-857 T (odd ratio
      [OR], 1.826; 95% confidence interval [CI], 1.097-3.039), TNF-alpha-863 A (OR,
      1.788; 95% CI, 1.079-2.905) and TNF-alpha-1031 C (OR, 1.912; 95% CI, 1.152-3.171)
      was associated with increased risk for gastric ulcer development. Carriage of the
      alleles TNF-alpha-857 T (OR, 1.686; 95% CI, 1.003-2.832), TNF-alpha-863 A (OR,
      1.863; 95% CI, 1.118-3.107) and TNF-alpha-1031 C (OR 2.074; 95% CI, 1.244-3.457)
      was also associated with increased risk of gastric cancer development. There was
      no relationship between the development of H. pylori-related diseases and
      polymorphisms of IL-1beta-511/-31 and TNF-alpha-308. The simultaneous carriage of
      three different high-producer alleles of TNF-alpha-857/-863/-1031 significantly
      increased the risk of gastric ulcer (OR, 6.57; 95% CI, 2.34-18.40) and gastric
      cancer (OR, 5.20; 95% CI, 1.83-14.78). CONCLUSIONS: Polymorphisms in TNF-alpha
      rather than IL-1beta are associated with increased risk for gastric ulcers and
      gastric cancer in Japan. The simultaneous carriage of more than one high-producer
      allele of TNF-alpha further increased the risks for gastric ulcer and cancer.

PMID- 17201882
TI  - Efficacy of rifabutin-based triple therapy in Helicobacter pylori infected
      patients after two standard treatments.
AB  - BACKGROUND AND AIM: Even with the current most effective treatment regimens for
      Helicobacter pylori infection, a considerable number of patients will be
      resistant to eradication. The aim of the present study was to evaluate the H.
      pylori eradication rate in patients resistant to standard therapies when treated
      with a triple therapy of pantoprazole, rifabutin and amoxicillin. METHODS: Ninety
      two consecutive patients diagnosed with H. pylori infection resistant to two
      previous treatment regimens were treated with pantoprazole, rifabutin and
      amoxicillin for 10 days. The persistence or eradication of H. pylori was
      determined by a 13C-urea breath test performed 4 weeks after the treatment.
      RESULTS: Per protocol eradication was achieved in 62.2% of patients and the
      intention-to-treat eradication was 60.8%. Only two patients were excluded for
      adverse events related to the treatment. CONCLUSIONS: The eradication rate is
      acceptable as a third-line therapy, particularly in centers with high cure rate
      for first line therapy. Another important value of this study is the good
      tolerance for the treatment observed in our patients. It is possible that
      rifabutin-based triple therapy may be of use in hospital centers that do not have
      disposable culture and susceptibility methods against H. pylori.

PMID- 17201883
TI  - Colonic amoebiasis and spirochetosis: morphological, ultrastructural and
      microbiological evaluation.
AB  - BACKGROUND: The present study reports on a prompt diagnosis of colonic amoebiasis
      with colonic spirochetosis by Brachyspira aalborgi and B. pilosicoli; such
      diagnosis allowed exclusion of other diseases and resolution of the case after
      specific treatment. METHODS AND RESULTS: A 37-year-old Italian man with a history
      of several months' mucosal diarrhea travelled to Greece, Romania and Tunisia.
      After his last trip he presented with an increase of up to 3-5 discharges daily,
      associated with bloody diarrhea, supporting the clinical suspect of inflammatory
      bowel disease. Colonoscopy revealed erosions from the cecum to the rectum, and
      ulcers both in the descending and sigmoid colon. Structures resembling amoebic
      trophozoites and sinusoidal microorganisms were observed in the colonic biopsies
      at histopathology and electron microscopy. Entamoeba histolytica DNA was detected
      by small-subunit rDNA polymerase chain reaction (PCR) from feces, rectal biopsies
      and isolated trophozoites. Spirochetes were identified from feces, colonic
      biopsies and cultures using a 16S rDNA restriction fragment length polymorphism
      PCR specific for the detection of B. aalborgi and B. pilosicoli. After therapy,
      the patient was restored to health. CONCLUSIONS: The rapid identification of E.
      histolytica, B. aalborgi and B. pilosicoli using traditional and specific and
      sensitive molecular methods permitted an accurate diagnosis and a specific
      therapy. It is suggested that mixed infection by parasites and spirochetes might
      occur more frequently than expected: it would be of extreme interest and
      importance to intensify clinical findings, and one infection should not prompt
      the pathologist/clinician to stop looking.

PMID- 17201884
TI  - Analysis of differential gene expression between chronic hepatitis B patients and
      asymptomatic hepatitis B carriers.
AB  - BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection remains a serious
      global health problem, inducing a spectrum of diseases, including asymptomatic
      HBV carriage (ASC) and chronic hepatitis B (CHB). ASC and CHB represent different
      immunological states and their prognoses are diverse. To clarify molecular
      mechanisms underlying the two infection states, the differentially expressed
      genes between the two states were screened and identified. METHODS: Subtracted
      complementary DNA libraries by suppression subtractive hybridization, dot blot
      hybridization and quantitative real-time PCR were used to identify the
      differentially expressed genes between subjects with CHB and those with ASC.
      RESULTS: RNA from peripheral blood mononuclear cells from CHB and ASC subjects
      was subjected to suppression subtractive hybridization and resulted in isolation
      of subtracted complementary DNA clones. Eighty-eight randomly sampled clones were
      rescreened by dot blot hybridization, from which 29 clones were identified as
      differentially expressed genes. The differential expression of three genes was
      confirmed by real-time PCR in 23 subjects with CHB and 21 with ASC. CONCLUSIONS:
      Differentially expressed genes in peripheral blood mononuclear cells between CHB
      and ASC have been isolated by suppression subtractive hybridization, including
      some new genes. Of the up-regulated genes in CHB, most are known to be responsive
      to inflammatory conditions. These genes might provide clues in elucidating the
      mechanisms of the two different HBV infection states and designing therapeutic
      targets for HBV infection.

PMID- 17201886
TI  - Multiple viral hepatitis in injection drug users and associated risk factors.
AB  - BACKGROUND: While infections due to hepatitis B virus (HBV) and hepatitis C virus
      (HCV) have been well-studied in injection drug users (IDUs), hepatitis A virus
      (HAV) infection and coinfection with multiple hepatitis viruses have received
      less attention. METHODS: Hepatitis serology as well as sociodemographic and drug
      related parameters were explored in patients (n = 1512) admitted for opiate
      detoxification. RESULTS: Antibodies to HAV were positive in 57.7%, to HBV in
      53.0%, and to HCV in 75.0% of the sample. Lack of any hepatic marker was reported
      in 11.2%; one marker was positive in 24.7%; two markers were positive in 31.2%;
      and all markers were positive in 32.9%. In patients with one positive marker,
      58.8% had had exposure to HCV, and 27% had exposure to HAV. In patients with two
      positive markers, 46.7% were HAV/HCV and 41.8% HBV/HCV antibody positive.
      Presence of HBV and HCV antibodies was associated with older age, longer duration
      of (i.v.) heroin use, and a higher number of rehabilitation treatment episodes
      (anova), current coconsumption of cocaine was associated with presence of
      antibodies to either HAV, HBV, and HCV. CONCLUSIONS: Coinfection with hepatic
      viruses is highly relevant in IDUs, although HAV does not necessarily share the
      same risk factors relevant for HBV or HCV transmission. The need for outreach
      vaccination programs is emphasized for HAV and HBV in the target population.
      Primary prevention should be implemented before initiation or at early stages of
      a drug career. Epidemiology and transmission of HAV in IDUs requires further
      research.

PMID- 17201885
TI  - Immune response in addicts with chronic hepatitis C treated with interferon and
      ribavirin.
AB  - BACKGROUND: The role played by the immune system in the progression of chronic
      hepatitis C (CHC) is not completely clear. Opioids may facilitate the outbreak of
      infections through marked immunomodulating effects on the immune response against
      a virus. To asses if addicts can be treated successfully with interferon (IFN)
      during detoxification treatment, we evaluated some immune response mediators in
      addicts affected by CHC. METHOD: A cohort of heroin users with CHC were enrolled
      during the detoxification period, divided into two groups and treated with IFN
      pegilate plus ribavirin (group A treated during methadone administration and
      group B treated at week 8 after methadone treatment completed). A group of
      patients with CHC and no history of drug addiction were enrolled as controls.
      Leukocyte subpopulation NK, CD4+, CD8+ and some cytokines Th1 (IFNgamma,
      interleukin [IL]2) and Th2 (IL-6, IL-10) were evaluated prior to, during and
      after methadone treatment. Sustained virological response was evaluated 24 weeks
      after antiviral treatment was completed. RESULTS: During methadone treatment,
      significantly (P < 0.05) higher cytokine Th1 and NK and lower cytokine Th2 levels
      were observed in groups A and B compared with levels obtained before treatment in
      the same groups. Relapse occurred at 56 +/- 8 weeks in 34/55 group A patients, at
      24 +/- 8 weeks in 33/52 group B patients and at 24 +/- 4 weeks in group C, there
      being a significant difference (P < 0.05) between group A and B and between group
      A and C. No significant differences between all groups were detected in CD4+ and
      CD8+ cell counts. CONCLUSIONS: Our results revealed that drug addicts with CHC
      can be treated successfully with IFN pegilate and ribavirin. This therapy can be
      recommended during the early phase of detoxification treatment to achieve a
      sustained response.

PMID- 17201887
TI  - Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric
      oxide synthesis.
AB  - BACKGROUND: The arginine-degrading enzyme, arginine deiminase conjugated to
      polyethylene glycol (ADI-SS PEG 20,000 mw), reduces extracellular arginine, has
      minimal toxicity, decreases tumor burden and improves liver function in patients
      with chronic hepatitis C virus infection (HCV) and inoperable hepatocellular
      carcinoma (HCC). Reduced extracellular arginine inhibits viral replication
      through unknown mechanisms. It is hypothesized that ADI-SS PEG 20,000 mw reduces
      HCV viral titers through nitric oxide (NO)-dependent effects. METHODS: The
      effects of ADI-SS PEG 20,000 mw (dose, 160 IU/m2; three cycles of four once
      weekly i.m. injections) on HCV titers, serum NO and plasma arginine, were
      evaluated using archived plasma from patients with HCC and HCV and in vitro cell
      model measurements of HCV replication. RESULTS: ADI-SS PEG 20,000 mw selectively
      inhibited HCV replication in vitro (IC50 = 0.027 IU/mL). Fifteen HCC/HCV patients
      completed treatment. The HCV titers were reduced by up to 99% in five out of 10
      (50%) HCV-serotype 1b patients (P = 0.0093). These patients also experienced
      significant improvements in liver function (P = 0.0091). There were concomitant
      reductions of plasma arginine and serum NO levels. The HCV titer was not reduced
      in HCV-type 2c patients. CONCLUSION: Reduction of extracellular arginine by ADI
      SS PEG 20,000 mw in HCC patients reduces HCV viral titers and improves liver
      function, possibly through suppression of NO.

PMID- 17201888
TI  - Excess mortality of hepatocellular carcinoma and morbidity of liver cirrhosis and
      hepatitis in HCV-endemic areas in an HBV-endemic country: geographic variations
      among 502 villages in southern Taiwan.
AB  - AIMS: The aim of this study was to investigate excess mortality for
      hepatocellular carcinoma (HCC) and prevalence of hepatitis and liver cirrhosis
      (LC) in hepatitis C virus (HCV)-endemic areas in Taiwan, which is a hepatitis B
      virus (HBV)-endemic country. METHODS: Tainan County, located in southern Taiwan,
      consists of 533 villages in 31 townships. A total of 56 702 subjects >or= 40
      years old (mean age, 60.9 +/- 11.8 years) were enrolled from 502 of the 533
      villages between April and November 2004 (n >or= 20/village). Serum blood HBV
      surface antigen (HBsAg), antibody to HCV (anti-HCV) and alanine transaminase
      (ALT) levels and platelet counts were measured. Township-specific mortality for
      liver cancer (ICD = 155) for both sexes between 1992 and 2001 were obtained from
      official publications. RESULTS: The prevalence of anti-HCV in Tainan County was
      10.2% (township range, 2.6-30.9%; village range, 0-90.5%). The prevalence of
      HBsAg was 10.9% (township range, 5.5-17.2%; village range, 0-30.8%). The
      prevalence of hypertransaminemia (serum ALT > 40 IU/L) was 12.8%. At township
      levels, prevalence of anti-HCV (r2 = 0.92, P < 0.001), HBsAg and anti-HCV
      (multiple r2 = 0.94) were correlated with hypertransaminemia prevalence by single
      and multiple linear analysis, respectively. At village levels, prevalence of anti
      HCV (r2 = 0.52, P < 0.001), HBsAg and anti-HCV (multiple r2 = 0.53) were each
      correlated with prevalence of hypertransaminemia, respectively. The prevalence of
      thrombocytopenia (<150,000 platelets/microL) was 5.5%, and adopted as a surrogate
      prevalence for LC. At township levels, prevalence of anti-HCV (r2 = 0.58) was the
      only factor correlated by multivariate analysis with prevalence of
      thrombocytopenia. At village levels, prevalence of anti-HCV and female-to-male
      ratio (multiple r2 = 0.43) were each independently associated with prevalence of
      thrombocytopenia. At township levels, HBsAg prevalence (r2 = 0.42) was more
      correlated with HCC mortality than anti-HCV prevalence (r2 = 0.28) for male
      subjects, while anti-HCV prevalence (r2 = 0.45) was more correlated with HCC
      mortality than HBsAg prevalence (r2 = 0.14) for female subjects. Prevalence of
      HBV and HCV infection were associated by multivariate analysis with both male
      (multiple r2 = 0.62) and female (multiple r2 = 0.53) HCC mortality. CONCLUSIONS:
      Prevalence of anti-HCV showed significant correlations with prevalence of
      hypertransaminemia, thrombocytopenia and liver cancer mortality. The findings
      indicate excessive mortality due to HCC, and LC and hepatitis prevalence in HCV
      endemic areas in Taiwan, an HBV-endemic country.

PMID- 17201889
TI  - Antifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver
      fibrosis.
AB  - BACKGROUND: Anti-inflammation strategies are one of the proposed therapeutic
      approaches to hepatic fibrosis. Tetrandrine (C(38)H(42)O(8)N(2), molecular
      weight: 622; Tet), an alkaloid isolated from the Chinese medicinal herb Stephania
      tetrandra, has been shown to exert anti-inflammatory activity in pulmonary
      diseases. The purpose of the present study was to investigate the in vitro and in
      vivo effects of Tet on hepatic fibrosis. METHODS: A cell line of rat hepatic
      stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF
      beta1) or tumor necrosis factor-alpha (TNF-alpha). The inhibitory effects of Tet
      on the nuclear factor kappaB (NFkappaB) signaling cascade and molecular markers
      including intercellular adhesion molecule-1 (ICAM-1) and alpha-smooth muscle
      actin (alpha-SMA) secretion were assessed. Fibrosis was induced by
      dimethylnitrosamine (DMN) administration in rats for 4 weeks. Fibrotic rats were
      randomly assigned to one of the four groups: vehicle (0.7% carboxyl methyl
      cellulose, CMC), Tet (1 mg/kg), Tet (5 mg/kg), or silymarin (50 mg/kg), each
      given by gavage twice daily for 3 weeks starting after 1 week of DMN
      administration. At the end of the study, liver tissues were scored for fibrosis
      and analyzed for molecular markers of fibrosis. RESULTS: Tetrandrine (0.5-5.0
      micromol/L) concentration-dependently inhibited NFkappaB transcriptional activity
      induced by TNF-alpha, including IkappaBalpha phosphorylation and mRNA expressions
      of ICAM-1 in HSC-T6 cells. In addition, Tet also inhibited TGF-beta1-induced
      alpha-SMA secretion and collagen deposition in HSC-T6 cells. Fibrosis scores of
      livers from DMN-treated rats with high-dose Tet (1.3 +/- 0.3) were significantly
      reduced in comparison with DMN-treated rats receiving saline (2.0 +/- 0.2).
      Hepatic collagen content of DMN rats was significantly reduced by either Tet or
      silymarin treatment. Double-staining results showed that alpha-SMA- and NFkappaB
      positive cells were decreased in the fibrotic livers by Tet and silymarin
      treatment. In addition, mRNA expression of ICAM-1, alpha-SMA, and TGF-beta1 was
      attenuated by Tet treatment. Moreover, levels of plasma aspartate
      aminotransferase and alanine aminotransferase activities were reduced by Tet and
      silymarin treatment. CONCLUSION: Tetrandrine exerts antifibrotic effects in both
      HSC-T6 cells and in rats with DMN-induced fibrosis.

PMID- 17201890
TI  - Evaluation of platelet kinetics in patients with liver cirrhosis: similarity to
      idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: Thrombocytopenia is a common manifestation of liver cirrhosis (LC),
      but its underlying mechanism is not fully understood. The purpose of the present
      paper was to evaluate the platelet kinetics in LC patients by examining several
      non-invasive convenient markers. METHODS: Fifty-seven LC patients, 32 patients
      with idiopathic thrombocytopenic purpura (ITP), 12 with aplastic anemia (AA), and
      29 healthy individuals were studied. Plasma thrombopoietin was measured by enzyme
      linked immunosorbent assay. Absolute reticulated platelet (RP) count and plasma
      glycocalicin were used as indices for thrombopoiesis, and the indices for
      platelet turnover were the RP proportion and the plasma glycocalicin normalized
      to the individual platelet count (GCI). RESULTS: There was no difference in
      thrombopoietin levels between LC patients and healthy controls. The RP proportion
      and GCI were significantly higher and the absolute RP count and glycocalicin
      significantly lower in LC patients than in healthy controls. These markers in ITP
      and LC patients were comparable, but significantly different from those in AA
      patients. The bone marrow megakaryocyte density in LC and ITP patients was
      similar, and significantly higher than in AA patients. CONCLUSIONS: Cirrhotic
      thrombocytopenia is a multifactorial condition involving accelerated platelet
      turnover and moderately impaired thrombopoiesis. Thrombopoietin deficiency is
      unlikely to be the primary contributor to cirrhotic thrombocytopenia.

PMID- 17201891
TI  - Risk factors for liver transplantation waiting list mortality.
AB  - BACKGROUND AND AIM: The gap between the demand for liver transplantation and
      organ donation rates has a major impact on waiting list mortality. Understanding
      the risk factors that predict liver transplant waiting list death may help
      optimize organ allocation policy and reduce waiting list deaths. METHODS: We
      analyzed risk factors associated with waiting list mortality in the Liver
      Transplant Unit Victoria for the period 1988 through 2004. RESULTS: The mean
      annual waiting list mortality for the period examined was 10.2% (10.6% for adult
      and 6.4% for pediatric patients). Factors associated with waiting list death
      included female sex, fulminant hepatic failure, primary non-function, blood group
      O, more urgent United Network for Organ Sharing (UNOS)-derived medical status, a
      Child-Turcotte-Pugh (CTP) score >or=11, a model for end-stage liver disease
      (MELD) score >or=20, and a pediatric end-stage liver disease score >or=20. UNOS
      derived medical status, CTP class, and MELD score were significant at the
      multivariate level. CONCLUSIONS: Disease severity scores, such as MELD, predict
      the risk of liver transplantation waiting list mortality. Use of such scores in
      organ allocation in Australian liver transplant units may result in reduced
      waiting list mortality.

PMID- 17201892
TI  - Effect of bile duct obstruction on the expression of intestinal mRNA related to
      cholesterol and bile acid metabolism in the rat.
AB  - BACKGROUND AND AIM: The liver and small intestine play an important role in
      maintaining cholesterol and bile acid balance within the body. The purpose of
      this study was to evaluate the effect of bile duct ligation (BDL) on the
      expression of intestinal and hepatic genes that are important for cholesterol and
      bile acid metabolism. METHODS: Rats were allocated to the BDL group or the sham
      operation group. Blood, liver and small intestine were obtained after 24, 72 and
      168 h from both groups. Serum and hepatic lipids were measured by colorimetric
      assays and hepatic and intestinal mRNA related to lipid metabolism was studied by
      reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Hepatic
      apolipoprotein (Apo) AIV, multidrug resistant protein (Mrp)2, adenosine
      triphosphate (ATP) binding cassette transporter (Abc)g5 and Abcg8 expression
      constantly decreased after BDL. Intestinal Apo AIV, Apo CIII, Mrp2, Abcg5 and
      Abcg8 expression remarkably decreased 24 h after BDL and recovered 72 and 168 h
      after BDL. Hepatic small heterodimer partner (Shp) expression did not change
      after BDL. Conversely, intestinal Shp expression remarkably decreased 24 h after
      BDL (16% of sham operation) and slightly recovered 168 h after BDL (58% of sham
      operation). CONCLUSION: Several intestinal mRNA expressions important for lipid
      (Apo AIV, Apo CIII, Abcg5 and Abcg8) and bile acid (Mrp2 and Shp) metabolism were
      decreased in the early phase of obstructive jaundice and the expression of these
      intestinal mRNA recovered in the late phase of obstructive jaundice.

PMID- 17201893
TI  - Education and imaging. Gastrointestinal: cecal ileus.

PMID- 17201894
TI  - Education and imaging. Hepatobiliary and pancreatic: gas-forming pyogenic liver
      abscess.

PMID- 17201895
TI  - Education and imaging. Gastrointestinal: ischemic colitis with thrombosis of the
      inferior mesenteric vein.

PMID- 17201896
TI  - Education and imaging. Hepatobiliary and pancreatic: percutaneous liver biopsy
      complicated by hemothorax.

PMID- 17201897
TI  - Education and imaging. Gastrointestinal: Whipple's disease.

PMID- 17201898
TI  - Intestinal tuberculosis mimicking fistulizing Crohn's disease.
AB  - A patient is reported with intestinal tuberculosis that mimicked fistulizing
      Crohn's disease endoscopically. He had complete resolution of symptoms after a
      full course of antituberculosis therapy. Gastroenterologists and general
      physicians should aware of the possibility of intestinal tuberculosis in areas
      with a high prevalence of tuberculosis infection.

PMID- 17201899
TI  - Low dose amiodarone associated cirrhosis.

PMID- 17201900
TI  - Adenoendocrine cell carcinoma of the gallbladder: differentiation of the
      endocrine component.

PMID- 17201901
TI  - Participant satisfaction with fecal occult blood test screening for colorectal
      cancer.

PMID- 17201902
TI  - Isolated gastric metastasis from renal cell carcinoma 10 years after radical
      nephrectomy.

PMID- 17201904
TI  - Protocol for the smoking, nicotine and pregnancy (SNAP) trial: double-blind,
      placebo-randomised, controlled trial of nicotine replacement therapy in
      pregnancy.
AB  - BACKGROUND: Smoking in pregnancy remains a public health challenge. Nicotine
      replacement therapy (NRT) is effective for smoking cessation in non-pregnant
      people, but because women metabolise nicotine and cotinine much faster in
      pregnancy, it is unclear whether this will be effective for smoking cessation in
      pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking,
      nicotine and pregnancy (SNAP) trial will investigate whether or not nicotine
      replacement therapy (NRT) is effective, cost-effective and safe when used for
      smoking cessation by pregnant women. METHODS/DESIGN: Over two years, in 5 trial
      centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be
      randomised as they attend hospital for ante-natal ultrasound scans. Women will
      receive either nicotine or placebo transdermal patches with behavioural support.
      The primary outcome measure is biochemically-validated, self-reported, prolonged
      and total abstinence from smoking between a quit date (defined before
      randomisation and set within two weeks of this) and delivery. At six months after
      childbirth self-reported maternal smoking status will be ascertained and two
      years after childbirth, self-reported maternal smoking status and the behaviour,
      cognitive development and respiratory symptoms of children born in the trial will
      be compared in both groups. DISCUSSION: This trial is designed to ascertain
      whether or not standard doses of NRT (as transdermal patches) are effective and
      safe when used for smoking cessation during pregnancy.

PMID- 17201905
TI  - Barriers to apply cardiovascular prediction rules in primary care: a postal
      survey.
AB  - BACKGROUND: Although cardiovascular prediction rules are recommended by
      guidelines to evaluate global cardiovascular risk for primary prevention, they
      are rarely used in primary care. Little is known about barriers for application.
      The objective of this study was to evaluate barriers impeding the application of
      cardiovascular prediction rules in primary prevention. METHODS: We performed a
      postal survey among general physicians in two Swiss Cantons by a purpose designed
      questionnaire. RESULTS: 356 of 772 dispatched questionnaires were returned
      (response rate 49.3%). About three quarters (74%) of general physicians rarely or
      never use cardiovascular prediction rules. Most often stated barriers to apply
      prediction rules among rarely- or never-users are doubts concerning over
      simplification of risk assessment using these instruments (58%) and potential
      risk of (medical) over-treatment (54%). 57% report that the numerical information
      resulting from prediction rules is often not helpful for decision-making in
      practice. CONCLUSION: If regular application of cardiovascular prediction rules
      in primary care is in demand additional interventions are needed to increase
      acceptance of these tools for patient management among general physicians.

PMID- 17201906
TI  - Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers.
AB  - BACKGROUND: Many breast, pancreatic, colonic and non-small-cell lung carcinoma
      lines express CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen, CEA), and
      antibodies to both can affect tumor cell growth in vitro and in vivo. Here, we
      compare both antigens as a function of histological phenotype in breast,
      pancreatic, lung, ovarian, and prostatic cancers, including patient-matched
      normal, primary tumor, and metastatic breast and colonic cancer specimens.
      METHODS: Antigen expression was determined by immunohistochemistry (IHC) using
      tissue microarrays with MN-15 and MN-3 antibodies targeting the A1B1- and N
      domains of CEACAM6, respectively, and the MN-14 antibody targeting the A3B3
      domain of CEACAM5. IHC was performed using avidin-biotin-diaminobenzide staining.
      The average score +/- SD (0 = negative/8 = highest) for each histotype was
      recorded. RESULTS: For all tumors, the amount of CEACAM6 expressed was greater
      than that of CEACAM5, and reflected tumor histotype. In breast tumors, CEACAM6
      was highest in papillary > infiltrating ductal > lobular > phyllodes; in
      pancreatic tumors, moderately-differentiated > well-differentiated > poorly
      differentiated tumors; mucinous ovarian adenocarcinomas had almost 3-fold more
      CEACAM6 than serous ovarian adenocarcinomas; lung adenocarcinomas > squamous
      tumors; and liver metastases of colonic carcinoma > primary tumors = lymph nodes
      metastases > normal intestine. However, CEACAM6 expression was similar in
      prostate cancer and normal tissues. The amount of CEACAM6 in metastatic colon
      tumors found in liver was higher than in many primary colon tumors. In contrast,
      CEACAM6 immunostaining of lymph node metastases from breast, colon, or lung
      tumors was similar to the primary tumor. CONCLUSION: CEACAM6 expression is
      elevated in many solid tumors, but variable as a function of histotype. Based on
      previous work demonstrating a role for CEACAM6 in tumor cell migration, invasion
      and adhesion, and formation of distant metastases (Blumenthal et al., Cancer Res
      65: 8809-8817, 2005), it may be a promising target for antibody-based therapy.

PMID- 17201908
TI  - Thickening of the pulmonary artery wall in acute intramural hematoma of the
      ascending aorta.
AB  - BACKGROUND: The occurrence of pulmonary artery obstruction in the course of acute
      aortic dissection is an unusual complication. The mechanism implicated is the
      rupture of the outer layer of the aorta and the subsequent hemorrhage into the
      adventitia of the pulmonary artery that causes its wall thickening and, at times,
      produces extrinsic obstruction of the vessel. There are no reports of this
      complication in acute intramural hematoma. CASE PRESENTATION: An 87-year-old
      woman was admitted to the hospital in shock after having had severe chest pain
      followed by syncope. An urgent transesophageal echocardiogram revealed the
      presence of acute intramural hematoma, no evidence of aortic dissection, severe
      pericardial effusion with cardiac tamponade, and periaortic hematoma that
      involved the pulmonary artery generating circumferential wall thickening of its
      trunk and right branch with no evidence of flow obstruction. Urgent surgery was
      performed but the patient died in the operating room. The post mortem
      examination, in the operating room, confirmed that there was an extensive
      hematoma around the aorta and beneath the adventitial layer of the pulmonary
      artery, with no evidence of flow obstruction. CONCLUSION: This is the first time
      that this rare complication is reported in the scenario of acute intramural
      hematoma and with the transesophageal echocardiogram as the diagnostic tool.

PMID- 17201907
TI  - Gene expression profiles of primary colorectal carcinomas, liver metastases, and
      carcinomatoses.
AB  - BACKGROUND: Despite the fact that metastases are the leading cause of colorectal
      cancer deaths, little is known about the underlying molecular changes in these
      advanced disease stages. Few have studied the overall gene expression levels in
      metastases from colorectal carcinomas, and so far, none has investigated the
      peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the
      present study is to investigate and compare the gene expression patterns of
      primary carcinomas (n = 18), liver metastases (n = 4), and carcinomatoses (n =
      4), relative to normal samples from the large bowel. RESULTS: Transcriptome
      profiles of colorectal cancer metastases independent of tumor site, as well as
      separate profiles associated with primary carcinomas, liver metastases, or
      peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of
      chromosome arm 5p are common in peritoneal carcinomatoses and several candidate
      genes (including PTGER4, SKP2, and ZNF622) mapping to this region were
      overexpressed in the tumors. Expression signatures stratified on TP53 mutation
      status were identified across all tumors regardless of stage. Furthermore, the
      gene expression levels for the in vivo tumors were compared with an in vitro
      model consisting of cell lines representing all three tumor stages established
      from one patient. CONCLUSION: By statistical analysis of gene expression data
      from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are
      able to identify genetic patterns associated with the different stages of
      tumorigenesis.

PMID- 17201910
TI  - Radiosensitization by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide
      under oxia and hypoxia in human colon cancer cells.
AB  - BACKGROUND: The sensitizing effects of 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline
      1,4-dioxide (DCQ) and ionizing radiation (IR) were determined in four colon
      cancer cells and in FHs74Int normal intestinal cells. METHODS: Cell cycle
      modulation, TUNEL assay, clonogenic survival and DNA damage were examined under
      oxia or hypoxia. Effects on apoptotic molecules and on p-Akt and Cox-2 protein
      expression were investigated. RESULTS: The four cell lines responded differently
      to DCQ+IR; HT-29 cells were most resistant. Combination treatment caused
      significant increases in preG1 (apoptosis) in HCT-116, while G2/M arrest occurred
      in DLD-1. DCQ potentiated IR effects more so under hypoxia than oxia. Pre
      exposure of DLD-1 to hypoxia induced 30% apoptosis, and G2/M arrest in oxia. The
      survival rate was 50% lower in DCQ+IR than DCQ alone and this rate further
      decreased under hypoxia. FHs74Int normal intestinal cells were more resistant to
      DCQ+IR than cancer cells.Greater ssDNA damage occurred in DLD-1 exposed to DCQ+IR
      under hypoxia than oxia. In oxia, p-Akt protein expression increased upon IR
      exposure and drug pre-treatment inhibited this increase. In contrast, in hypoxia,
      exposure to IR reduced p-Akt protein and DCQ restored its expression to the
      untreated control. Apoptosis induced in hypoxic DLD-1 cells was independent of
      p53-p21 modulation but was associated with an increase in Bax/Bcl-2 ratio and the
      inhibition of the Cox-2 protein. CONCLUSION: DCQ is a hypoxic cell
      radiosensitizer in DLD-1 human colon cancer cells.

PMID- 17201909
TI  - Oesophageal cancer mortality in Spain: a spatial analysis.
AB  - BACKGROUND: Oesophageal carcinoma is one of the most common cancers worldwide.
      Its incidence and mortality rates show a wide geographical variation at a world
      and regional level. Geographic mapping of age-standardized, cause-specific death
      rates at a municipal level could be a helpful and powerful tool for providing
      clues leading to a better understanding of its aetiology. METHODS: This study
      sought to describe the geographic distribution of oesophageal cancer mortality
      for Spain's 8077 towns, using the autoregressive spatial model proposed by Besag,
      York and Mollie. Maps were plotted, depicting standardised mortality ratios,
      smoothed relative risk (RR) estimates, and the spatial pattern of the posterior
      probability of RR being greater than 1. RESULTS: Important differences associated
      with area of residence were observed in risk of dying from oesophageal cancer in
      Spain during the study period (1989-1998). Among men, excess risk appeared across
      the north of the country, along a band spanning the length of the Cantabrian
      coastline, Navarre, the north of Castile & Leon and the north-west of La Rioja.
      Excess risk was likewise observed in the provinces of Cadiz and part of Seville
      in Andalusia, the islands of Tenerife and Gran Canaria, and some towns in the
      Barcelona and Gerona areas. Among women, there was a noteworthy absence of risk
      along the mid-section of the Cantabrian seaboard, and increases in mortality, not
      observed for men, in the west of Extremadura and south-east of Andalusia.
      CONCLUSION: These major gender- and area-related geographical differences in risk
      would seem to reflect differences in the prevalence of some well-established and
      modifiable risk factors, including smoking, alcohol consumption, obesity and
      diet. In addition, excess risks were in evidence for both sexes in some areas,
      possibly suggesting the implication of certain local environmental or socio
      cultural factors. From a public health standpoint, small-area studies could be
      very useful for identifying locations where epidemiological research and
      intervention measures ought to receive priority, given the potential for reducing
      risk in certain places.

PMID- 17201911
TI  - In silico whole-genome screening for cancer-related single-nucleotide
      polymorphisms located in human mRNA untranslated regions.
AB  - BACKGROUND: A promising application of the huge amounts of genetic data currently
      available lies in developing a better understanding of complex diseases, such as
      cancer. Analysis of publicly available databases can help identify potential
      candidates for genes or mutations specifically related to the cancer phenotype.
      In spite of their huge potential to affect gene function, no systematic attention
      has been paid so far to the changes that occur in untranslated regions of mRNA.
      RESULTS: In this study, we used Expressed Sequence Tag (EST) databases as a
      source for cancer-related sequence polymorphism discovery at the whole-genome
      level. Using a novel computational procedure, we focused on the identification of
      untranslated region (UTR)-localized non-coding Single Nucleotide Polymorphisms
      (UTR-SNPs) significantly associated with the tumoral state. To explore possible
      relationships between genetic mutation and phenotypic variation, bioinformatic
      tools were used to predict the potential impact of cancer-associated UTR-SNPs on
      mRNA secondary structure and UTR regulatory elements. We provide a comprehensive
      and unbiased description of cancer-associated UTR-SNPs that may be useful to
      define genotypic markers or to propose polymorphisms that can act to alter gene
      expression levels. Our results suggest that a fraction of cancer-associated UTR
      SNPs may have functional consequences on mRNA stability and/or expression.
      CONCLUSION: We have undertaken a comprehensive effort to identify cancer
      associated polymorphisms in untranslated regions of mRNA and to characterize
      putative functional UTR-SNPs. Alteration of translational control can change the
      expression of genes in tumor cells, causing an increase or decrease in the
      concentration of specific proteins. Through the description of testable
      candidates and the experimental validation of a number of UTR-SNPs discovered on
      the secreted protein acidic and rich in cysteine (SPARC) gene, this report
      illustrates the utility of a cross-talk between in silico transcriptomics and
      cancer genetics.

PMID- 17201912
TI  - Intravital imaging of fluorescent markers and FRET probes by DNA tattooing.
AB  - BACKGROUND: Advances in fluorescence microscopy and mouse transgenesis have made
      it possible to image molecular events in living animals. However, the generation
      of transgenic mice is a lengthy process and intravital imaging requires
      specialized knowledge and equipment. Here, we report a rapid and undemanding
      intravital imaging method using generally available equipment. RESULTS: By DNA
      tattooing we transfect keratinocytes of living mice with DNA encoding fluorescent
      biosensors. Subsequently, the behavior of individual cells expressing these
      biosensors can be visualized within hours and using conventional microscopy
      equipment. Using this "instant transgenic" model in combination with a corrected
      coordinate system, we followed the in vivo behavior of individual cells
      expressing either FRET- or location-based biosensors for several days. The
      utility of this approach was demonstrated by assessment of in vivo caspase-3
      activation upon induction of apoptosis. CONCLUSION: This "instant skin
      transgenic" model can be used to follow the in vivo behavior of individual cells
      expressing either FRET- or location-based probes for several days after tattooing
      and provides a rapid and inexpensive method for intravital imaging in murine
      skin.

PMID- 17201913
TI  - Bronchiolitis obliterans organizing pneumonia (BOOP) after thoracic radiotherapy
      for breast carcinoma.
AB  - Common complications of thoracic radiotherapy include esophagitis and radiation
      pneumonitis. However, it is important to be aware of uncommon post-radiotherapy
      complications such as bronchiolitis obliterans organizing pneumonia (BOOP). We
      report on two patients with carcinoma of the breast who developed an interstitial
      lung disease consistent with BOOP. BOOP responds to treatment with
      corticosteroids and the prognosis is generally good despite of the need for long
      term administration of corticosteroids as relapses can occur during tapering of
      steroids. This report provides guidelines for the evaluation and treatment of
      patients with pulmonary infiltrates after radiotherapy.

PMID- 17201914
TI  - Identification of amino acid residues involved in substrate specificity of plant
      acyl-ACP thioesterases using a bioinformatics-guided approach.
AB  - BACKGROUND: The large amount of available sequence information for the plant acyl
      ACP thioesterases (TEs) made it possible to use a bioinformatics-guided approach
      to identify amino acid residues involved in substrate specificity. The Conserved
      Property Difference Locator (CPDL) program allowed the identification of putative
      specificity-determining residues that differ between the FatA and FatB TE
      classes. Six of the FatA residue differences identified by CPDL were incorporated
      into the FatB-like parent via site-directed mutagenesis and the effect of each on
      TE activity was determined. Variants were expressed in E. coli strain K27 that
      allows determination of enzyme activity by GCMS analysis of fatty acids released
      into the medium. RESULTS: Substitutions at four of the positions (74, 86, 141,
      and 174) changed substrate specificity to varying degrees while changes at the
      remaining two positions, 110 and 221, essentially inactivated the thioesterase.
      The effects of substitutions at positions 74, 141, and 174 (3-MUT) or 74, 86,
      141, 174 (4-MUT) were not additive with respect to specificity. CONCLUSION: Four
      of six putative specificity determining positions in plant TEs, identified with
      the use of CPDL, were validated experimentally; a novel colorimetric screen that
      discriminates between active and inactive TEs is also presented.

PMID- 17201915
TI  - Vitamin E and selenium plasma concentrations in weanling pigs under field
      conditions in Norwegian pig herds.
AB  - BACKGROUND: The status of alpha-tocopherol (vit E) and selenium (Se) has been
      shown to influence disease resistance in pigs, and may be important for the
      health of weanling pigs. METHODS: Plasma levels of both vit E and Se were
      followed in weanling pigs under field conditions in six Norwegian pig herds.
      Plasma vit E and Se were measured in 3 sows from each herd and 4 piglets in the
      litter of each sow at the day before weaning (day -1); and in the same piglets at
      days 4, 8 and 18 after weaning. RESULTS: Mean plasma vit E was 4.0 microg/ml in
      the sows and 2.6 microg/ml in the piglets at day -1, fell to 1.6 microg/ml in the
      weanling pigs at day 4, and remained low. Mean plasma Se was 0.22 microg/g in the
      sows and 0.08 microg/g in the piglets at day -1, rose to 0.10 microg/g in the
      weanlings at day 4, and continued rising. CONCLUSION: The results suggest that
      vit E and Se supplementation to piglets and weanling pigs in Norway may still be
      suboptimal, but that levels of the two nutrients partially compensate for each
      other in the weaning period.

PMID- 17201916
TI  - Ethnomedicine and dominant medicine in multicultural Australia: a critical
      realist reflection on the case of Korean-Australian immigrants in Sydney.
AB  - BACKGROUND: Viewed through the micro focus of an interpretive lens, medical
      anthropology remains mystified because interpretivist explanations seriously
      downplay the given context in which individual health seeking-behaviours occur.
      This paper draws upon both the interpretivist and political economy perspectives
      to reflect on the ethno medical practices within the Korean-Australian community
      in Sydney. METHODS: We draw on research data collected between 1995 and 1997 for
      an earlier study of the use of biomedical and traditional medicine by Korean
      Australians in Sydney. A total of 120 interviews were conducted with a range of
      participants, including biomedical doctors, traditional health professionals,
      Korean community leaders and Korean migrants representing a range of socio
      economic backgrounds and migration patterns. RESULTS AND DISCUSSION: First, the
      paper highlights the extent to which the social location of migrants in a host
      society alters or restructures their initial cultural practices they bring with
      them. Second, taking hanbang medicine in the Korean-Australian community as an
      illustrative case, the paper explores the transformation of the dominant
      biomedicine in Australia as a result of the influx of ethnomedicine in the era of
      global capitalism and global movement. CONCLUSION: In seeking to explain the
      popularity and supply of alternative health care, it is important to go beyond
      the culture of each kind of health care itself and to take into consideration the
      changes occurring at societal, national and global levels as well as
      consequential individual response to the changes. New social conditions influence
      the choice of health care methods, including herbal/alternative medicine, health
      foods and what are often called New Age therapies.

PMID- 17201917
TI  - Occlusion, TMDs, and dental education.
AB  - The paradigmatic shift to evidence-based dentistry (EBD) that relates to occlusal
      therapy, selective occlusal adjustment (OA) and stabilization splints therapy
      (SS) for TMDs has had an unfavourable impact on the teaching of many of the
      important aspects of occlusion needed in dental practice. The teaching of OA
      systematically in dental schools has been nearly abandoned because of the belief
      that OA is an irreversible procedure and gives the impression that it is without
      merit elsewhere in the management of occlusion. However, a particular dose of
      knowledge and practice of occlusion that is necessary for all aspects of dental
      care should be taught systematically in dental schools. The uses and misuses of
      OA and SS and their limitations should be emphasized because of their importance
      to bring clinical reality into the dental curriculum. Thus, and irrespective of
      EBD induced contradictions, OA and SS should still have a significant place in
      systematically teaching of occlusal therapy. However, there are many more aspects
      of the management of occlusion that should to be considered. Hopefully, because
      of their importance, other aspects of the management of occlusion will once again
      become a significant part of the dental curriculum.

PMID- 17201918
TI  - SirT1 modulates the estrogen-insulin-like growth factor-1 signaling for postnatal
      development of mammary gland in mice.
AB  - INTRODUCTION: Estrogen and insulin-like growth factor-1 (IGF-1) play important
      roles in mammary gland development and breast cancer. SirT1 is a highly conserved
      protein deacetylase that can regulate the insulin/IGF-1 signaling in lower
      organisms, as well as a growing number of transcription factors, including NF
      kappaB, in mammalian cells. Whether SirT1 regulates the IGF-1 signaling for
      mammary gland development and function, however, is not clear. In the present
      study, this role of SirT1 was examined by studying SirT1-deficient mice. METHODS:
      SirT1-deficient (SirT1(ko/ko)) mice were generated by crossing a new strain of
      mice harboring a conditional targeted mutation in the SirT1 gene (SirT1(co/co))
      with CMV-Cre transgenic mice. Whole mount and histology analyses,
      immunofluorescence staining, immunohistochemistry, and western blotting were used
      to characterize mammary gland development in virgin and pregnant mice. The effect
      of exogenous estrogen was also examined by subcutaneous implantation of a slow
      releasing pellet in the subscapular region. RESULTS: Both male and female
      SirT1(ko/ko) mice can be fertile despite the growth retardation phenotype. Virgin
      SirT1(ko/ko) mice displayed impeded ductal morphogenesis, whereas pregnant
      SirT1(ko/ko) mice manifested lactation failure due to an underdeveloped
      lobuloalveolar network. Estrogen implantation was sufficient to rescue ductal
      morphogenesis. Exogenous estrogen reversed the increased basal level of IGF-1
      binding protein-1 expression in SirT1(ko/ko) mammary tissues, but not that of
      IkappaB alpha expression, suggesting that increased levels of estrogen enhanced
      the production of local IGF-1 and rescued ductal morphogenesis. Additionally,
      TNFalpha treatment enhanced the level of the newly synthesized IkappaB alpha in
      SirT1(ko/ko) cells. SirT1 deficiency therefore affects the cellular response to
      multiple extrinsic signals. CONCLUSION: SirT1 modulates the IGF-1 signaling
      critical for both growth regulation and mammary gland development in mice. SirT1
      deficiency deregulates the expression of IGF-1 binding protein-1 and attenuates
      the effect of IGF-1 signals, including estrogen-stimulated local IGF-1 signaling
      for the onset of ductal morphogenesis. These findings suggest that the enzymatic
      activity of SirT1 may influence both normal growth and malignant growth of
      mammary epithelial cells.

PMID- 17201919
TI  - Anthropometric measures and nutritional status in a healthy elderly population.
AB  - BACKGROUND: Anthropometric evaluation is an essential feature of geriatric
      nutritional evaluation for determining malnutrition, being overweight, obesity,
      muscular mass loss, fat mass gain and adipose tissue redistribution.
      Anthropometric indicators are used to evaluate the prognosis of chronic and acute
      diseases, and to guide medical intervention in the elderly. We evaluated
      anthropometric measurements and nutritional status as they relate to age and
      gender in healthy elderly people. METHODS: The study analyzed data from the
      national survey "Health needs and health service use by older-than-60-year-old
      beneficiaries of the Mexican Institute of Social Security (IMSS)". The present
      study included only individuals who reported no chronic disease in the last 20
      years and had no hospital admission in the two months prior to the survey.
      Anthropometric measurements included weight, height, body mass index (BMI), body
      circumference (arm, waist, hip and calf), waist to hip ratio (WHR), elbow
      amplitude and knee-heel length. RESULTS: Application of the inclusion criteria
      resulted in a study population elderly of 1,968, representing 12.2% of the
      original number in the national survey in urban areas beneficiaries of the IMSS.
      The study population comprised 870 women and 1,098 men, with a mean age of 68.6
      years. The average weights were 62.7 kg for women and 70.3 kg for men (p < 0.05),
      and the mean heights were 1.52 m for women and 1.63 m for men (p < 0.05). Age
      related changes in anthropometric values were identified. BMI values indicated
      that 62.3% of the population was overweight, and 73.6% of women and 16.5% of men
      had high fat tissue distribution. CONCLUSION: Our findings suggest that applying
      the BMI thresholds that identify being overweight in the general adult population
      may lead to an overestimation in the number of overweight elderly Similar
      problems appear to exist when assessing waist circumference and WHR values.
      Prospective studies are required to determine the associations between health and
      BMI, waist circumference and WHR in the elderly.

PMID- 17201920
TI  - How young can children reliably and validly self-report their health-related
      quality of life?: an analysis of 8,591 children across age subgroups with the
      PedsQL 4.0 Generic Core Scales.
AB  - BACKGROUND: The last decade has evidenced a dramatic increase in the development
      and utilization of pediatric health-related quality of life (HRQOL) measures in
      an effort to improve pediatric patient health and well-being and determine the
      value of healthcare services. The emerging paradigm shift toward patient-reported
      outcomes (PROs) in clinical trials has provided the opportunity to further
      emphasize the value and essential need for pediatric patient self-reported
      outcomes measurement. Data from the PedsQL DatabaseSM were utilized to test the
      hypothesis that children as young as 5 years of age can reliably and validly
      report their HRQOL. METHODS: The sample analyzed represented child self-report
      age data on 8,591 children ages 5 to 16 years from the PedsQL 4.0 Generic Core
      Scales DatabaseSM. Participants were recruited from general pediatric clinics,
      subspecialty clinics, and hospitals in which children were being seen for well
      child checks, mild acute illness, or chronic illness care (n = 2,603, 30.3%), and
      from a State Children's Health Insurance Program (SCHIP) in California (n =
      5,988, 69.7%). RESULTS: Items on the PedsQL 4.0 Generic Core Scales had minimal
      missing responses for children as young as 5 years old, supporting feasibility.
      The majority of the child self-report scales across the age subgroups, including
      for children as young as 5 years, exceeded the minimum internal consistency
      reliability standard of 0.70 required for group comparisons, while the Total
      Scale Scores across the age subgroups approached or exceeded the reliability
      criterion of 0.90 recommended for analyzing individual patient scale scores.
      Construct validity was demonstrated utilizing the known groups approach. For each
      PedsQL scale and summary score, across age subgroups, including children as young
      as 5 years, healthy children demonstrated a statistically significant difference
      in HRQOL (better HRQOL) than children with a known chronic health condition, with
      most effect sizes in the medium to large effect size range. CONCLUSION: The
      results demonstrate that children as young as the 5 year old age subgroup can
      reliably and validly self-report their HRQOL when given the opportunity to do so
      with an age-appropriate instrument. These analyses are consistent with recent FDA
      guidelines which require instrument development and validation testing for
      children and adolescents within fairly narrow age groupings and which determine
      the lower age limit at which children can provide reliable and valid responses
      across age categories.

PMID- 17201921
TI  - Yeast genomic expression patterns in response to low-shear modeled microgravity.
AB  - The low-shear microgravity environment, modeled by rotating suspension culture
      bioreactors called high aspect ratio vessels (HARVs), allows investigation in
      ground-based studies of the effects of microgravity on eukaryotic cells and
      provides insights into the impact of space flight on cellular physiology. We have
      previously demonstrated that low-shear modeled microgravity (LSMMG) causes
      significant phenotypic changes of a select group of Saccharomyces cerevisiae
      genes associated with the establishment of cell polarity, bipolar budding, and
      cell separation. However, the mechanisms cells utilize to sense and respond to
      microgravity and the fundamental gene expression changes that occur are largely
      unknown. In this study, we examined the global transcriptional response of yeast
      cells grown under LSMMG conditions using DNA microarray analysis in order to
      determine if exposure to LSMMG results in changes in gene expression. RESULTS:
      LSMMG differentially changed the expression of a significant number of genes
      (1372) when yeast cells were cultured for either five generations or twenty-five
      generations in HARVs, as compared to cells grown under identical conditions in
      normal gravity. We identified genes in cell wall integrity signaling pathways
      containing MAP kinase cascades that may provide clues to novel physiological
      responses of eukaryotic cells to the external stress of a low-shear modeled
      microgravity environment. A comparison of the microgravity response to other
      environmental stress response (ESR) genes showed that 26% of the genes that
      respond significantly to LSMMG are involved in a general environmental stress
      response, while 74% of the genes may represent a unique transcriptional response
      to microgravity. In addition, we found changes in genes involved in budding, cell
      polarity establishment, and cell separation that validate our hypothesis that
      phenotypic changes observed in cells grown in microgravity are reflected in
      genome-wide changes. This study documents a considerable response to yeast cell
      growth in low-shear modeled microgravity that is evident, at least in part, by
      changes in gene expression. Notably, we identified genes that are involved in
      cell signaling pathways that allow cells to detect environmental changes, to
      respond within the cell, and to change accordingly, as well as genes of unknown
      function that may have a unique transcriptional response to microgravity. We also
      uncovered significant changes in the expression of many genes involved in cell
      polarization and bud formation that correlate well with the phenotypic effects
      observed in yeast cells when grown under similar conditions. These results are
      noteworthy as they have implications for human space flight.

PMID- 17201922
TI  - Sequence and structural features of carbohydrate binding in proteins and
      assessment of predictability using a neural network.
AB  - BACKGROUND: Protein-Carbohydrate interactions are crucial in many biological
      processes with implications to drug targeting and gene expression. Nature of
      protein-carbohydrate interactions may be studied at individual residue level by
      analyzing local sequence and structure environments in binding regions in
      comparison to non-binding regions, which provide an inherent control for such
      analyses. With an ultimate aim of predicting binding sites from sequence and
      structure, overall statistics of binding regions needs to be compiled. Sequence
      based predictions of binding sites have been successfully applied to DNA-binding
      proteins in our earlier works. We aim to apply similar analysis to carbohydrate
      binding proteins. However, due to a relatively much smaller region of proteins
      taking part in such interactions, the methodology and results are significantly
      different. A comparison of protein-carbohydrate complexes has also been made with
      other protein-ligand complexes. RESULTS: We have compiled statistics of amino
      acid compositions in binding versus non-binding regions- general as well as in
      each different secondary structure conformation. Binding propensities of each of
      the 20 residue types and their structure features such as solvent accessibility,
      packing density and secondary structure have been calculated to assess their
      predisposition to carbohydrate interactions. Finally, evolutionary profiles of
      amino acid sequences have been used to predict binding sites using a neural
      network. Another set of neural networks was trained using information from single
      sequences and the prediction performance from the evolutionary profiles and
      single sequences were compared. Best of the neural network based prediction could
      achieve an 87% sensitivity of prediction at 23% specificity for all carbohydrate
      binding sites, using evolutionary information. Single sequences gave 68%
      sensitivity and 55% specificity for the same data set. Sensitivity and
      specificity for a limited galactose binding data set were obtained as 63% and 79%
      respectively for evolutionary information and 62% and 68% sensitivity and
      specificity for single sequences. Propensity and other sequence and structural
      features of carbohydrate binding sites have also been compared with our similar
      extensive studies on DNA-binding proteins and also with protein-ligand complexes.
      CONCLUSION: Carbohydrates typically show a preference to bind aromatic residues
      and most prominently tryptophan. Higher exposed surface area of binding sites
      indicates a role of hydrophobic interactions. Neural networks give a moderate
      success of prediction, which is expected to improve when structures of more
      protein-carbohydrate complexes become available in future.

PMID- 17201923
TI  - Parent proxy-report of their children's health-related quality of life: an
      analysis of 13,878 parents' reliability and validity across age subgroups using
      the PedsQL 4.0 Generic Core Scales.
AB  - BACKGROUND: Health-related quality of life (HRQOL) measurement has emerged as an
      important health outcome in clinical trials, clinical practice improvement
      strategies, and healthcare services research and evaluation. While pediatric
      patient self-report should be considered the standard for measuring perceived
      HRQOL, there are circumstances when children are too young, too cognitively
      impaired, too ill or fatigued to complete a HRQOL instrument, and reliable and
      valid parent proxy-report instruments are needed in such cases. Further, it is
      typically parents' perceptions of their children's HRQOL that influences
      healthcare utilization. Data from the PedsQL DatabaseSM were utilized to test the
      reliability and validity of parent proxy-report at the individual age subgroup
      level for ages 2-16 years as recommended by recent FDA guidelines. METHODS: The
      sample analyzed represents parent proxy-report age data on 13,878 children ages 2
      to 16 years from the PedsQL 4.0 Generic Core Scales DatabaseSM. Parents were
      recruited from general pediatric clinics, subspecialty clinics, and hospitals in
      which their children were being seen for well-child checks, mild acute illness,
      or chronic illness care (n = 3,718, 26.8%), and from a State Children's Health
      Insurance Program (SCHIP) in California (n = 10,160, 73.2%). RESULTS: The
      percentage of missing item responses for the parent proxy-report sample as a
      whole was 2.1%, supporting feasibility. The majority of the parent proxy-report
      scales across the age subgroups exceeded the minimum internal consistency
      reliability standard of 0.70 required for group comparisons, while the Total
      Scale Scores across the age subgroups approached or exceeded the reliability
      criterion of 0.90 recommended for analyzing individual patient scale scores.
      Construct validity was demonstrated utilizing the known groups approach. For each
      PedsQL scale and summary score, across age subgroups, healthy children
      demonstrated a statistically significant difference in HRQOL (better HRQOL) than
      children with a known chronic health condition, with most effect sizes in the
      medium to large effect size range. CONCLUSION: The results demonstrate the
      feasibility, reliability, and validity of parent proxy-report at the individual
      age subgroup for ages 2-16 years. These analyses are consistent with recent FDA
      guidelines which require instrument development and validation testing for
      children and adolescents within fairly narrow age groupings and which determine
      the lower age limit at which reliable and valid responses across age categories
      are achievable. Even as pediatric patient self-report is advocated, there remains
      a fundamental role for parent proxy-report in pediatric clinical trials and
      health services research.

PMID- 17201924
TI  - Expression of Cre recombinase in dopaminoceptive neurons.
AB  - BACKGROUND: Dopamine-activated signaling regulates locomotor and emotional
      responses and alterations in dopamine-signaling are responsible of several
      psychomotor disorders. In order to identify specific functions of these pathways,
      the Cre/loxP system has been used. Here, we describe the generation and the
      characterization of a transgenic mouse line expressing the Cre recombinase in
      dopaminoceptive neurons. To this purpose, we used as expression vector a 140 kb
      yeast artificial chromosome (YAC) containing the dopamine D1 receptor gene
      (Drd1a). RESULTS: In the chosen line, D1Cre, the spatio-temporal pattern of Cre
      expression closely recapitulated that of the endogenous Drd1a gene, as assessed
      by immunohistological approaches in embryonic and adult stages. Efficiency of
      recombination was confirmed by crossing D1Cre with three different loxP lines
      (Creb1loxP, CaMKIVloxP and GRloxP) and with the R26R reporter. In the three loxP
      lines studied, recombination was restricted to the area of Cre expression.
      CONCLUSION: In view of the patterns of recombination restricted to the major
      dopaminoceptive regions as seen in the context of the CREB, CaMKIV and GR
      mutations, the D1Cre line will be a useful tool to dissect the contributions of
      specific genes to biological processes involving dopamine signaling.

PMID- 17201926
TI  - Polymyxin B as inhibitor of LPS contamination of Schistosoma mansoni recombinant
      proteins in human cytokine analysis.
AB  - BACKGROUND: Recombinant proteins expressed in Escherichia coli vectors are
      generally contaminated with endotoxin. In this study, we evaluated the ability of
      Polymyxin B to neutralize the effect of LPS present as contaminant on Schistosoma
      mansoni recombinant proteins produced in E. coli in inducing TNF-alpha and IL-10.
      Peripheral blood mononuclear cells from individuals chronically infected with S.
      mansoni were stimulated in vitro with recombinant Sm22.6, Sm14 and P24 antigens
      (10 microg/mL) in the presence of Polymyxin B (10 microg/mL). RESULTS: The levels
      of cytokines were measured using ELISA. There was greater than 90% reduction (p <
      0.05) in the levels of TNF-alpha and IL-10 when Polymyxin B was added to the
      cultures stimulated with LPS. In cultures stimulated with S. mansoni recombinant
      proteins in the presence of Polymyxin B, a reduction in the levels of TNF-alpha
      and IL-10 was also observed. However, the percentage of reduction was lower when
      compared to the cultures stimulated with LPS, probably because these proteins are
      able to induce the production of these cytokines by themselves. CONCLUSION: This
      study showed that Polymyxin B was able to neutralize the effect of endotoxin, as
      contaminant in S. mansoni recombinant antigens produced in E. coli, in inducing
      TNF-alpha and IL-10 production.

PMID- 17201928
TI  - Estimation of the stress related to conservative scoliosis therapy: an analysis
      based on BSSQ questionnaires.
AB  - BACKGROUND: Adolescent girls treated with a brace for scoliosis are submitted to
      prolonged stress related to both the disease and the therapy. Currently proposed
      quality of life questionnaires are focused on the outcome of therapy. Bad
      Sobernheim Stress Questionnaire (BSSQ) enables monitoring of patients being under
      treatment with a brace or exercises. The aim of the study was to assess the
      stress level in conservatively managed scoliotic girls using BSSQ. MATERIALS AND
      METHODS: 111 girls, aged 14.2 +/- 2.2 years, mean Cobb angle of the primary curve
      42.8 degrees +/- 17.0 degrees and mean Bunnell angle of 11.4 degrees +/- 4.5
      degrees were examined with two versions of BSSQ (Deformity and Brace). The
      analysis considered the type of treatment, curve location, correlation of the
      total score with age, Cobb angle and Bunnell rotation angle. RESULTS: The BSSQ
      Deformity revealed the median of 17 points in patients managed with exercises
      (from 4 to 24 points), 18 in patients managed with a brace (from 8 to 24 points)
      and 12 in patients before surgery (from 3 to 21 points). Braced patients who
      completed both questionnaires (n = 50) revealed significantly higher score with
      BSSQ Deformity (median = 18) comparing to BSSQ Brace (median = 9). There was a
      correlation between the total score of BSSQ Deformity and the Cobb angle (r = 
      0.34), Bunnell primary curve rotation (r = -0.34) and Bunnell sum of rotation (r
      = -0.33) but not with the age of patients. CONCLUSION: Scoliotic adolescents
      managed with exercises and brace suffered little stress from the deformity. The
      brace increased the level of stress over the stress induced by the deformity. The
      stress level correlated with clinical deformity (Bunnell angle), radiological
      deformity (Cobb angle) and the type of treatment (exercises, bracing, surgery).
      Bad Sobernheim Stress Questionnaires are simple and helpful in the management of
      girls treated conservatively for idiopathic scoliosis.

PMID- 17201927
TI  - Prevalence of human papillomavirus genotypes and their variants in high risk West
      Africa women immigrants in South Italy.
AB  - BACKGROUND: The distribution of human papillomaviruses (HPVs) varies greatly
      across populations and HPV surveys have been performed in different geographical
      regions in order to apply appropriate vaccine strategies. Little information,
      however, exists regarding HPV genotypes distribution in immigrant women from
      countries at high incidence for cervical cancer. The aim of this study was to
      determine the spectrum of HPVs and their variants among HIV-positive and HIV
      negative women immigrants in South Italy mainly from West Africa and with a
      history of prostitution. RESULTS: Cervical cytological samples have been
      collected from 14 HIV-positive and 31 HIV-negative immigrants (38 out of 45 were
      born in Nigeria), attending a gynecological outpatient clinic in the Campania
      region. Human papillomaviruses were detected by broad spectrum consensus-primer
      pairs MY09/MY11 and GP5+/GP6+-based polymerase chain reaction and characterized
      by nucleotide sequence analysis. Altogether, 42.2% (19/45) of samples were HPV
      positive with detection rates of 57.1% (8/14) in HIV-positive and 35.5% (11/31)
      in HIV-negative women. Among the twelve different viral genotypes identified,
      HPV33, 58, 70 and 81 were the prevalent genotypes with a frequency of 6.7% each,
      followed by HPV16, 35, 42, 54, 31, 52, 56 and 67, in descending order of
      prevalence. Sequence homology studies performed on the L1 amplified fragments of
      HPV16, 52 and 58 isolates allowed the identification of nucleotide changes
      distinctive of non-European variants. CONCLUSION: The overall HPV prevalence
      (42.2%) was high in this immigrant women group with the most common viral types
      other than HPV16 and 18, against which current vaccine strategies have been
      developed. The distribution of HPV genotypes and their variants in high-risk
      immigrants reflects that of their original countries. The surveillance of risk
      groups that may act as viral reservoirs of uncommon genotypes within different
      countries are necessary to determine the severity of HPV infection with the
      different viral types and to monitor a possible shift of prevalent strains
      following vaccination.

PMID- 17201925
TI  - Pancreatic islet cell therapy for type I diabetes: understanding the effects of
      glucose stimulation on islets in order to produce better islets for
      transplantation.
AB  - While insulin replacement remains the cornerstone treatment for type I diabetes
      mellitus (T1DM), the transplantation of pancreatic islets of Langerhans has the
      potential to become an important alternative. And yet, islet transplant therapy
      is limited by several factors, including far too few donor pancreases. Attempts
      to expand mature islets or to produce islets from stem cells are far from
      clinical application. The production and expansion of the insulin-producing cells
      within the islet (so called beta cells), or even creating cells that secrete
      insulin under appropriate physiological control, has proven difficult. The
      difficulty is explained, in part, because insulin synthesis and release is
      complex, unique, and not entirely characterized. Understanding beta-cell function
      at the molecular level will likely facilitate the development of techniques to
      manufacture beta-cells from stem cells. We will review islet transplantation, as
      well as the mechanisms underlying insulin transcription, translation and glucose
      stimulated insulin release.

PMID- 17201929
TI  - Detection of weakly conserved ancestral mammalian regulatory sequences by primate
      comparisons.
AB  - BACKGROUND: Genomic comparisons between human and distant, non-primate mammals
      are commonly used to identify cis-regulatory elements based on constrained
      sequence evolution. However, these methods fail to detect functional elements
      that are too weakly conserved among mammals to distinguish them from non
      functional DNA. RESULTS: To evaluate a strategy for large scale genome annotation
      that is complementary to the commonly used distal species comparisons, we
      explored the potential of deep intra-primate sequence comparisons. We sequenced
      the orthologs of 558 kb of human genomic sequence, covering multiple loci
      involved in cholesterol homeostasis, in 6 non-human primates. Our analysis
      identified six non-coding DNA elements displaying significant conservation among
      primates but undetectable in more distant comparisons. In vitro and in vivo tests
      revealed that at least three of these six elements have regulatory function.
      Notably, the mouse orthologs of these three functional human sequences had
      regulatory activity despite their lack of significant sequence conservation,
      indicating that they are ancestral mammalian cis-regulatory elements. These
      regulatory elements could be detected even in a smaller set of three primate
      species including human, rhesus and marmoset. CONCLUSION: We have demonstrated
      that intra-primate sequence comparisons can be used to identify functional
      modules in large genomic regions, including cis-regulatory elements that are not
      detectable through comparison with non-mammalian genomes. With the available
      human and rhesus genomes and that of marmoset, which is being actively sequenced,
      this strategy can be extended to the whole genome in the near future.

PMID- 17201931
TI  - Cervical mature teratoma 17 years after initial treatment of testicular
      teratocarcinoma: report of a late relapse.
AB  - BACKGROUND: Late relapses of testicular germ cell tumor are uncommon. We report a
      case of cervical mature teratoma appeared 17 years after treatment of testicular
      teratocarcinoma. CASE PRESENTATION: A 20-year-old patient underwent left sided
      orchiectomy followed by systemic therapy and retroperitoneal residual mass
      resection in 1989. He remained in complete remission for 200 months. In 2005 a
      huge left supraclavicular neck mass with extension to anterior mediastinum
      appeared. Radical surgical resection of the mass was performed and pathologic
      examination revealed mature teratoma. CONCLUSION: This is one of the longest long
      term reported intervals of a mature teratoma after treatment of a testicular
      nonseminoma germ cell tumor. This case emphasizes the necessity for follow up of
      testicular cancer throughout the patient's life.

PMID- 17201930
TI  - The co-evolved Helicobacter pylori and gastric cancer: trinity of bacterial
      virulence, host susceptibility and lifestyle.
AB  - Helicobacter pylori is an important yet unproven etiological agent of gastric
      cancer. H. pylori infection is more prevalent in developing Asian countries like
      India and it is usually acquired at an early age. It has been two decades since
      Marshall and Warren (1984) first described curved bacilli in the stomach of ulcer
      and gastritis patients. This discovery has won them the Nobel Prize recently, but
      the debate whether H. pylori is a pathogen or a commensal organism is still hot.
      Associations with disease-specific factors remain elusive years after the genome
      sequences were made available. Cytotoxin-associated antigen A (CagA) and the so
      called plasticity region cluster genes are implicated in pathogenesis of the
      carcinoma of stomach. Another virulence factor VacA whose role is still
      debatable, has recently been projected in pathology of gastric cancer. Studies of
      the evolution through genetic variation in H. pylori populations have provided a
      window into the history of human population migrations and a possible co
      evolution of this pathogen with its human host. Possible symbiotic relationships
      were seriously debated since the discovery of this pathogen. The debate has been
      further intensified as some studies proposed H. pylori infection to be beneficial
      in some humans. In this commentary, we attempt to briefly discuss about H. pylori
      as a human pathogen, and some of the important issues linked to its
      pathophysiology in different hosts. 'We dance around in a ring and suppose, the
      secret sits in the middle and knows'--Robert Frost.

PMID- 17201932
TI  - Asymptomatic schwannoma of the heart.
AB  - We present a case of an asymptomatic right atrial mass detected on a screening
      ECHO. Pre-operative imaging and intraoperative frozen section suggested an atrial
      myxoma, but the extracardiac nature of the mass and its adherence to the right
      superior pulmonary vein and interatrial septum were inconsistent with this.
      Detailed histological assessment confirmed the diagnosis of atrial schwannoma.
      Limited case reports have shown complete resection is curative.

PMID- 17201933
TI  - Factors associated with premature mortality among young injection drug users in
      Vancouver.
AB  - BACKGROUND: Young injection drug users (IDUs) may be at increased risk of
      premature mortality due to the health risks associated with injection drug use
      including overdoses and infections. However, there has been little research
      conducted on mortality causes, rates and associations among this population. We
      undertook this study to investigate patterns of premature mortality, prior to age
      30 years, among young IDUs. METHODS: Since 1996, 572 young (< or = 29 years) IDUs
      have been enrolled in the Vancouver Injection Drug Users Study (VIDUS). Semi
      annually, participants have completed an interviewer-administered questionnaire
      and have undergone serologic testing for HIV and hepatitis C (HCV). Mortality
      data have been continually updated through linkages with the Provincial Coroner's
      Office. Crude and age-specific mortality rates, standardized mortality ratios,
      and life expectancy measures were calculated using person-time methods.
      Predictors of mortality were identified using Cox regression analyses. FINDINGS:
      Twenty-two participants died prior to age 30 years during the follow-up period
      for an overall crude mortality rate of 1,368 per 100,000 person-years. Overall,
      young IDUs were 16.4 times (95% confidence interval [CI]; 9.1-27.1) more likely
      to die; young women IDUs were 54.1 times (95%CI; 29.6-90.8) and young men IDUs
      were 12.9 times (95%CI; 5.5, 25.3) more likely to die when compared to the
      Canadian non-IDU population of the same age. The leading observed cause of death
      among females was: homicide (N = 9); and among males: suicide (N = 3) and
      overdose (N = 3). In Cox regression analyses, factors associated with mortality
      were, HIV infection (Hazard Ratio [HR]: 4.55; CI: 1.92-10.80) and sex work (HR:
      2.76; CI: 1.16-6.56). INTERPRETATION: Premature mortality was 13 and 54 times
      higher among young men and women who use injection drugs in Vancouver than among
      the general population in Canada. The majority of deaths among the women were
      attributable to homicide, suggesting that interventions should occur not only
      through harm reduction services but also through structural interventions at the
      legal and policy level.

PMID- 17201935
TI  - A model worth considering?
AB  - A business-science hybrid model for medical research that focuses on
      collaboration rather than competition seems worth exploring.

PMID- 17201934
TI  - The chemokine and chemokine receptor superfamilies and their molecular evolution.
AB  - The human chemokine superfamily currently includes at least 46 ligands, which
      bind to 18 functionally signaling G-protein-coupled receptors and two decoy or
      scavenger receptors. The chemokine ligands probably comprise one of the first
      completely known molecular superfamilies. The genomic organization of the
      chemokine ligand genes and a comparison of their sequences between species shows
      that tandem gene duplication has taken place independently in the mouse and human
      lineages of some chemokine families. This means that care needs to be taken when
      extrapolating experimental results on some chemokines from mouse to human.

PMID- 17201936
TI  - Harry Potter and the structural biologist's (Key)stone.

PMID- 17201937
TI  - Moonlight in Vermont illuminates plant development.

PMID- 17201939
TI  - The challenge of overactive bladder therapy: alternative to antimuscarinic
      agents.
AB  - Contemporary, the management of overactive bladder (OAB), a medical condition
      characterized by urgency, with or without urge urinary incontinence, frequency
      and nocturia, in absence of genitourinary pathologies or metabolic factors that
      could explain these symptoms, is complex, and a wide range of conservative
      treatments has been offered, including bladder training, biofeedback, behavioral
      changes, oral or intravesical anticholinergic agents, S3 sacral neuromodulation
      and peripheral electrical stimulation. Clinical efficacy of these treatments
      remains an open issue and several experimental and clinical studies were carried
      out in the last years improving the results of medical treatment. Here we review
      the pathophysiology of micturition reflex, the current therapies for OAB and the
      rationale for alternative treatments. Furthermore we critically address the
      potential use of medications targeting the central nervous system (CNS) and the
      primary sensory nerves of the bladder wall, we review the use of agonists of
      nociceptin/orphanin protein (NOP) receptor and finally we report the results
      obtained by intradetrusor injection of botulinum toxin.

PMID- 17201940
TI  - Laparoscopic-assisted nephroureterectomy after radical cystectomy for
      transitional cell carcinoma.
AB  - OBJECTIVE: To report our experience with laparoscopic-assisted nephroureterectomy
      for upper tract transitional cell carcinomas after radical cystectomy and urinary
      diversion. MATERIALS AND METHODS: Seven patients (53-72 years-old) underwent
      laparoscopic-assisted nephroureterectomy 10 to 53 months after radical cystectomy
      for transitional cell carcinoma at our institution. Surgical technique, operative
      results, tumor features, and outcomes of all patients were retrospectively
      reviewed. RESULTS: Mean operative time was 305 minutes with a significant amount
      of time spent on the excision of the ureter from the urinary diversion. Estimate
      blood loss and length of hospital stay averaged 180 mL and 10.8 days,
      respectively. Intraoperative and postoperative complications occurred in two
      patients each. There was one conversion to open surgery. Pathology confirmed
      upper-tract transitional cell carcinoma in all cases. Metastatic disease occurred
      in two patients after a mean follow-up of 14.6 months. CONCLUSIONS:
      Nephrouretectomy following cystectomy is a complex procedure due to the altered
      anatomy and the presence of many adhesions. A laparoscopic-assisted approach can
      be performed safely in properly selected cases but does not yield the usual
      benefits seen with other laparoscopic renal procedures.

PMID- 17201941
TI  - Long-term results of simple enucleation for the treatment of small renal cell
      carcinoma.
AB  - OBJECTIVE: We have analyzed our institutional experience with simple enucleation
      for the treatment of small renal tumors for elective indications. MATERIALS AND
      METHODS: A total of 30 patients underwent elective nephron-sparing surgery (NSS)
      from May 1997 to January 2001. All patients underwent NSS by means of
      enucleation. The tumor bed was coagulated carefully for haemostatic and partly
      for oncological reasons. Median follow-up was 71 months (range: 49-91 months).
      RESULTS: Pathological review according to the 2002 TNM classification showed that
      70 % (21 of 30) of tumors were pT1a, 26.7 % (8 of 30) pT1b and 3.3 % (1 of 30)
      pT3a. Median tumor size was 3.7 cm. (range: 3.0 - 5.5 cm). There was no
      perioperative mortality (within the first 30 days). Bleeding had not been
      recorded during perioperative period. Urinary leakage was observed in 1 patient
      (3.3%). No case of local recurrence was observed. Five and 7-year cumulative
      survival was 96.6% and 93.3%, respectively. Five and 7-year cancer specific
      survival was 100% and 96.5%, respectively. CONCLUSIONS: Simple tumor enucleation
      is a safe and acceptable approach for elective NSS. It provides excellent long
      term progression-free and cancer specific survival rates, and is not associated
      with an increased risk of local recurrence compared to partial nephrectomy.

PMID- 17201942
TI  - Carcinoma of the renal pelvis and ureter.
AB  - OBJECTIVE: To assess the occurrence of upper urinary tract urothelial tumors
      (UUTT) in Brazil. MATERIALS AND METHODS: We performed a clinical and
      histopathologic study of 33 patients who were diagnosed with a malignant neoplasm
      in the renal pelvis or ureter in the period of 1994 to 2004, in a single
      institution. RESULTS: Among the patients with upper urinary tract carcinoma, 70%
      were males and 30% females, with mean age of 65 +/- 16 years (ranging from 31 to
      91 years). Nineteen patients presented renal pelvis tumor (58%), 9 ureteral tumor
      (27%) and 5 synchronic pelvic and ureteral tumors (15%). Renal pelvis tumors
      represented 2.8% of all the urothelial neoplasms, and 11.4% of all renal
      neoplasms treated in the same period. Ureteral tumors represented 1.6% of all the
      urothelial malignancies surgically managed in these 11 years. Tobacco smoking was
      the most common risk factor, and analgesic abuse was not reported by those
      patients. Most carcinomas were high-grade and muscle-invasive. Mean time to
      diagnosis was 7 months, being hematuria the most common symptom. CONCLUSIONS: A
      high association was also found between UUTT and bladder urothelial carcinoma.
      UUTT were mostly seen in men in their seventies and related to a high overall and
      cancer-related mortality rate. The overall disease-specific survival was 40%,
      much lower than found in most of the reported series.

PMID- 17201943
TI  - Extracorporeal shockwave lithotripsy versus ureteroscopy for distal ureteric
      calculi: efficacy and patient satisfaction.
AB  - OBJECTIVE: We compared the efficacy of extracorporeal shock wave lithotripsy
      (ESWL) and ureteroscopy (URS) for the treatment of distal ureteral calculi with
      respect to patient satisfaction. MATERIALS AND METHODS: This is a prospective
      study where a total of 212 patients with solitary, radiopaque distal ureteral
      calculi were treated with ESWL (n = 92) using Dornier lithotriptor S (MedTech
      Europe GmbH) or URS (n = 120). Patient and stone characteristics, treatment
      parameters, clinical outcomes, and patient satisfaction were assessed for each
      group. RESULTS: The 2 groups were comparable in regard to patient age, sex, stone
      size, and side of treatment. The stone-free status for ESWL and URS at 3 months
      was 81.5% and 97.5%, respectively (p < 0.0001). In addition, 88% of patients who
      underwent ESWL versus 20% who underwent URS were discharged home the day of
      procedure. Minor complications occurred in 3.3% and 8.3% of the ESWL and URS
      groups, respectively (p = 0.127). No ureteral perforation or stricture occurred
      in the URS group. Postoperative flank pain and dysuria were more severe in the
      URS than ESWL group, although the differences were not statistically significant
      (p = 0.16). Patient satisfaction was high for both groups, including 94% for URS
      and 80% for ESWL (p = 0.002). CONCLUSIONS: URS is more effective than ESWL for
      the treatment of distal ureteral calculi. ESWL was more often performed on an
      outpatient basis, and showed a trend towards less flank pain and dysuria, fewer
      complications and quicker convalescence. Patient satisfaction was significantly
      higher for URS according to the questionnaire used in this study.

PMID- 17201944
TI  - Microvascular invasion is an independent prognostic factor in patients with
      prostate cancer treated with radical prostatectomy.
AB  - OBJECTIVE: Current published data regarding the prognostic value of microvascular
      invasion (MVI) in patients with prostate cancer (PCa) have yielded mixed results.
      Furthermore, most important series had surgical procedures performed by multiple
      surgeons and surgical specimens analyzed by multiple pathologists. We determined
      the relation of MVI with other pathologic features and whether this finding can
      be used as an independent prognostic factor in patients with PCa. MATERIALS AND
      METHODS: We selected 428 patients with clinically localized PCa treated with
      radical prostatectomy (RP). MVI was correlated to other pathologic features. The
      Kaplan-Meier method was used to evaluate survival curves and statistical
      significance was determined by the log-rank test. Multivariate analysis was
      performed through a Cox proportional hazards regression model. RESULTS: Eleven
      percent out of the 428 patients presented MVI. Except for the lack of association
      with biopsy Gleason score, MVI was related to all clinical and pathologic
      features of RP specimens. Mean follow up after surgery was 53.9 +/- 20.1 months.
      Patients with MVI presented a recurrence rate of 44.6% compared to only 20.2% for
      patients without MVI (Log-rank test - p < 0.001). After Cox regression analysis,
      MVI was an independent prognostic feature related to biochemical recurrence.
      CONCLUSIONS: MVI is associated to advanced pathologic features of PCa and is an
      important prognostic factor regarding disease recurrence in patients treated with
      RP. These findings support the recommendations to the routine evaluation of this
      variable in pathologic reports of RP specimens.

PMID- 17201945
TI  - Splenosis. A diagnosis to be considered.
AB  - The term splenosis applies to the autotransplanted splenic tissue resulting from
      seeding in the context of past splenic trauma or surgery. We report a 42-year-old
      man with a history of splenectomy observed for an incidentally found retrovesical
      mass thought to be an ectopic testicle. The abdominal laparotomy revealed
      multiple focuses of pelvic splenosis. As splenosis can be diagnosed through
      specific imaging studies one should always consider it in differential diagnosis
      of a mass discovered years after splenic surgery or trauma.

PMID- 17201946
TI  - Urothelial-type adenocarcinoma of the prostate mimicking metastatic colorectal
      adenocarcinoma.
AB  - Adenocarcinoma arising in urinary bladder or prostatic urethra is uncommon. When
      they occur, the tumor can be mistaken for metastatic lesions, especially from the
      colon. Here we report the fifth case of a primary urothelial-type adenocarcinoma
      arising in the prostate which showed enteric differentiation. The patient was a
      55 year-old male whose prostatic needle core biopsy showed a high grade
      adenocarcinoma which was initially thought to be metastatic colon cancer. A
      follow-up colonoscopy was unremarkable. Subsequent prostatectomy revealed a high
      grade adenocarcinoma which was positive for cytokeratins 7 and 20,
      carcinoembryonic antigen, CDX2, and high molecular weight cytokeratin, and
      negative for prostate specific antigen, prostate specific acid phosphatase and
      AMACR. A diagnosis of urothelial-type adenocarcinoma of the prostate was
      rendered. We review the literature regarding this entity, and discuss the
      differential diagnosis, emphasizing utility of immunohistochemistry in making the
      diagnosis. Finally, we speculate on the behavior of these rare tumors.

PMID- 17201947
TI  - Elective appendicovesicostomy in association with Monfort abdominoplasty in the
      treatment of prune belly syndrome.
AB  - OBJECTIVE: To evaluate the role of elective appendicovesicostomy in association
      with Monfort abdominoplasty to avoid urinary tract infection (UTI) and renal
      damage in the post-operative follow-up of patients with prune belly syndrome.
      MATERIALS AND METHODS: We followed 4 patients operated in our institution
      (UNIFESP) (Monfort, orchidopexy and Mitrofanoff) and compared them to 2 patients
      treated similarly, but without an appendicovesicostomy, in a second institution
      (UFBA). We evaluated postoperative clinical complications, UTI and preservation
      of renal parenchyma. Patients were followed as outpatients with urinalysis,
      ultrasonography (US) and occasionally with renal scintigraphy. RESULTS: Mean
      follow-up was 23.5 months. Immediate post-operative course was uneventful. We
      observed that only one patient with the Mitrofanoff channel persisted with UTI,
      while the 2 patients used as controls persisted with recurrent pyelonephritis (>
      2 UTI year). CONCLUSION: Our data suggest that no morbidity was added by the
      appendicovesicostomy to immediate postoperative surgical recovery and that this
      procedure may have a beneficial effect in reducing postoperative UTI events and
      their consequences by reducing the postvoid residuals in the early abdominoplasty
      follow-up. However, we recognize that the series is small and only a longer
      follow-up with a larger number of patients will allow us to confirm our
      suppositions. We could not make any statistically significant assumptions
      regarding differences in renal preservation due to the same limitations.

PMID- 17201949
TI  - Pudendal nerve latency time in normal women via intravaginal stimulation.
AB  - INTRODUCTION & OBJECTIVES: Studies of motor conduction for the efferent
      functional assessment of the pudendal nerve in women with pelvic dysfunctions
      have been conducted through researching distal motor latency times. The
      transrectal approach has been the classic approach for this electrophysiological
      examination. The objective of the present study is to verify the viability of the
      transvaginal approach in performing the exam, to establish normal values for this
      method and to analyze the influence of age, stature and parity in the latency
      value of normal women. MATERIALS AND METHODS: A total of 23 volunteers without
      genitourinary pathologies participated in this study. In each, pudendal motor
      latency was investigated through the transvaginal approach, which was chosen due
      to patient's higher tolerance levels. RESULTS: The motor response represented by
      registering the M-wave was obtained in all volunteers on the right side (100%)
      and in 13 volunteers on the left side (56.5%). The mean motor latency obtained in
      the right and left was respectively: 1.99 +/- 0.41 and 1.92 +/- 0.48 milliseconds
      (ms). There was no difference between the sides (p = 0.66). Latency did not
      correlate with age, stature or obstetric history. The results obtained in the
      present study were in agreement with those found by other researchers using the
      transrectal approach. CONCLUSION: The vaginal approach represents an alternative
      for pudendal nerve distal motor latency time, with similar results to those
      achieved through the transrectal approach. Normative values obtained herein might
      serve as a comparative basis for subsequent physiopathological studies.

PMID- 17201948
TI  - Urogenital involvement in the Klippel-Trenaunay-Weber syndrome. Treatment options
      and results.
AB  - OBJECTIVE: Klippel-Trenaunay-Weber syndrome (KTWS) is a congenital condition
      characterized by vascular malformations of the capillary, venous and lymphatic
      systems associated to soft tissue and bone hypertrophy in the affected areas.
      This syndrome may involve bladder, kidney, urethra, ureter and genitals. We
      report the treatment of 7 KTWS patients with urogenital involvement. MATERIALS
      AND METHODS: From 1995 to 2005, 7 patients with KTWS were evaluated and the
      charts of these patients were reviewed. RESULTS: Patients' median age was 19
      years (range 4 to 46-years) and only 1 was female. The clinical presentation
      included genital deformities in 3 cases, hematuria in 2 and urethrorragia in 2,
      one of which associated with cryptorchidism and phimosis. Three patients had an
      association of pelvic and genital malformations, including 2 patients with
      hematuria due to vesical lesions and 1 patient with left ureterohydronephrosis
      due to a pelvic mass. Two patients had urethral lesions. Treatment included
      endoscopic laser coagulation for 1 patient with recurrent hematuria and 1 patient
      with urethrorrhagia, pelvic radiotherapy for 1 patient with hematuria and
      circumcision in 2 patients with genital deformities. One patient required
      placement of a double-J catheter to relieve obstruction. Hematuria and
      urethrorragia were safely and effectively controlled with laser applications.
      Circumcision was also effective. The patient treated with radiotherapy developed
      a contracted bladder and required a continent urinary diversion. CONCLUSIONS:
      Urogenital involvement in patients with KTWS is not rare and must be suspected in
      the presence of hematuria or significant cutaneous deformity of the external
      genitalia. Surgical treatment may be warranted in selected cases.

PMID- 17201950
TI  - Technique of kidney transplantation in mice with anti-reflux urinary
      reconstruction.
AB  - Experimental models of organ transplantation play a crucial role in establishing
      the principles of transplantation immunobiology. Murine transplant models of
      vascularized organs are particularly useful for immunobiological studies because
      there are more immunological tools available. However, the technique of kidney
      transplant in mice is very challenging. A difficult aspect of this model is
      urinary reconstruction, which is frequently associated to complications. In this
      article, the technique of mouse kidney transplantation using an anti-reflux
      system (modified extravesical ureteroneocystostomy) is described and illustrated
      for the first time. Although technically demanding, this procedure is feasible
      and may reduce the incidence of urine leakage and reflux.

PMID- 17201971
TI  - Susceptibility of Plodia interpunctella (Lepidoptera: Pyralidae) developmental
      stages to high temperatures used during structural heat treatments.
AB  - Heating the ambient air of a whole, or a portion of a food-processing facility to
      50 to 60 degrees C and maintaining these elevated temperatures for 24 to 36 h, is
      an old technology, referred to as heat treatment. There is renewed interest in
      adopting heat treatments around the world as a viable insect control alternative
      to fumigation with methyl bromide. There is limited published information on
      responses of the Indian meal moth, Plodia interpunctella (Hubner), exposed to
      elevated temperatures typically used during heat treatments. Time-mortality
      relationships were determined for eggs, fifth-instars (wandering-phase larvae),
      pupae, and adults of P. interpunctella exposed to five constant temperatures
      between 44 and 52 degrees C. Mortality of each stage increased with increasing
      temperature and exposure time. In general, fifth-instars were the most heat
      tolerant stage at all temperatures tested. Exposure for a minimum of 34 min at 50
      degrees C was required to kill 99% of the fifth-instars. It is proposed that heat
      treatments aimed at controlling fifth-instars should be able to control all other
      stages of P. interpunctella.

PMID- 17201972
TI  - Longevity and pheromone output in stored-product Bostrichidae.
AB  - Information on longevity and on the effect of ageing on pheromone signalling in
      Bostrichidae infesting stored products is important because pheromones play a
      crucial role in mediating aggregation by the species in storages. The longevity
      of starved and unstarved Prostephanus truncatus (Horn) and Rhyzopertha dominica
      (Fabricius) were determined at 28+/-1 degrees C, 65+/-2% RH and L12:D12 cycle.
      Additionally, the effects of ageing on rate of pheromone emission were
      investigated in R. dominica by comparing emission rates of the aggregation
      pheromones Dominicalure-1 (DL1) and Dominicalure-2 (DL2) released by adult males
      ranging from 4, 8, 12, 24 and 48 weeks of age. Mean survival time of starved male
      and female P. truncatus was 8.6+/-0.6 and 9.1+/-0.4 days, respectively. Starved
      R. dominica males lived for 5.7+/-0.2 days, and females for 4.7+/-0.1 days.
      However, mean survival times were not significantly different for starved males
      vs. females of either species. Mean survival time of unstarved male and female P.
      truncatus was 27.5+/-2.0 and 18.0+/-3.3 weeks, respectively, and for unstarved
      male and female R. dominica was 26.1+/-2.8 and 16.7+/-2.9 weeks, respectively.
      Difference in mean survival times of unstarved males vs. females in both P.
      truncatus and R. dominica were significant. Between species, no significant
      difference was observed in mean survival time between unstarved males of P.
      truncatus or R. dominica, nor between females of both species. Rate of pheromone
      emission in R. dominica was higher when the insects were relatively young (4, 8
      and 12 weeks old), but declined by almost 55% in treatments where the insect were
      at about 24 or 48 weeks old, suggesting that recruitment potential of R. dominica
      might reduce substantially as the insects age.

PMID- 17201974
TI  - Differential effect of Agaricus host species on the population development of
      Megaselia halterata (Diptera: Phoridae).
AB  - Twelve isolates from the genus Agaricus (Fungi, Basidiomycota) were investigated
      for their ability to support development of the phorid fly, Megaselia halterata
      (Wood), which is an important pest of the commercial white button mushroom
      Agaricus bisporus. Combined effects of oviposition of adult female M. halterata
      and larval development in mushroom compost inoculated with Agaricus mycelium were
      determined using bioassays. The numbers of M. halterata offspring that developed
      were affected by the Agaricus isolate used, and there was a significant
      separation between resistant and susceptible isolates. In a bioassay where the
      female phorids had a choice of all 12 isolates for oviposition, three isolates
      produced >200 adults per 100 g compost pot while the remaining nine isolates had
      <20 adults per pot. Where there was no choice of Agaricus isolate for
      oviposition, five isolates resulted in >100 adults per 100 g compost pot while
      the remainder resulted in <4 adults per pot. With the susceptible isolates, there
      was a positive correlation between increasing concentration of mycelium in the
      substrate and phorid development until the concentration exceeded 40% after which
      numbers of emerging phorids declined. Genetic identity of Agaricus isolates was
      determined using ITS sequencing and phylogenetic methods, which revealed two
      major cluster groups. Isolates supporting the development of large populations of
      M. halterata were located in one of these clusters (group I), and were either
      Agaricus bisporus or other species from the same Agaricus section Duploannulatae.
      Isolates that did not support the development of M. halterata populations were
      located in a different cluster (group II) and were more genetically distant from
      A. bisporus, e.g. Agaricus sections Arvenses, Minores and Xanthodermatei. Species
      of Agaricus with resistance to M. halterata could have significant potential for
      the breeding and cultivation of phorid-free mushrooms.

PMID- 17201973
TI  - Diversity of lepidopteran stem borers on monocotyledonous plants in eastern
      Africa and the islands of Madagascar and Zanzibar revisited.
AB  - Surveys were completed in Eritrea, Ethiopia, Kenya, Madagascar, Mozambique,
      Tanzania, Uganda and Zanzibar to assess the lepidopteran stem borer species
      diversity on wild host plants. A total of 24,674 larvae belonging to 135 species
      were collected from 75 species of wild host plants belonging to the Poaceae,
      Cyperaceae and Typhaceae. Amongst them were 44 noctuid species belonging to at
      least nine genera, 33 crambids, 15 pyralids, 16 Pyraloidea species not yet
      identified, 25 tortricids and three cossids. The noctuid larvae represented 73.6%
      of the total number of larvae collected, with 66.3, 3.5 and 3.8% found on
      Poaceae, Cyperaceae and Typhaceae, respectively. The Crambidae, Pyralidae,
      Tortricidae and Cossidae represented 19.8, 1.9, 2.5 and 0.1% of the total larvae
      collected, respectively, with 90.4% of the Crambidae and Pyralidae collected from
      Poaceae, and 99.7% of the Tortricidae collected from Cyperaceae. The lepidopteran
      stem borer species diversity in the wild host plants was far more diverse than
      previously reported.

PMID- 17201975
TI  - Microsatellite marker analysis of peach-potato aphids (Myzus persicae, Homoptera:
      Aphididae) from Scottish suction traps.
AB  - The peach-potato aphid Myzus persicae (Sulzer) is an important vector of plant
      viruses. A network of suction traps collects aerial samples of this aphid in
      order to monitor and help predict its spatial distribution and likely impact on
      virus transmission in crops. A suction trap catch is thought to be a good
      representation of the total aphid pool. Sensitive molecular markers have been
      developed that determine the genetic composition of the M. persicae population.
      In Scotland, UK, these were applied to field collections revealing a limited
      number of clones. Molecular markers are less successful when applied to specimens
      that have been preserved in an ethanol-based trap fluid designed to preserve
      morphology. An assessment of different DNA extraction and PCR techniques is
      presented and the most efficient are used to analyse M. persicae specimens caught
      in the Dundee suction trap in 2001, a year when exceptionally high numbers were
      caught. The results reveal that the majority of the M. persicae caught belonged
      to two highly insecticide resistant clones. In addition, it was possible to
      compare the relative frequencies of genotypes caught in the trap with those
      collected at insecticide treated and untreated field sites in the vicinity. These
      results indicate that, in addition to suction trap data, the ability to sample
      field sites provides valuable early warning data which have implications for pest
      control and virus management strategies.

PMID- 17201977
TI  - Effects of cattle treatment with a cypermethrin/cymiazol spray on survival and
      reproduction of the dung beetle species Euoniticellus intermedius (Coleoptera:
      Scarabaeidae).
AB  - In a bioassay to determine non-target ecotoxicological effects of a pyrethroid
      spray (Ektoban) on dung beetles, dung from both cypermethrin/cymiazol-treated and
      control cattle was collected one, two, three, five, seven, 14, 21 and 28 days
      after treatment and fed to a treatment and control group (respectively) of
      beetles of the species Euoniticellus intermedius (Reiche). This was done to
      assess whether a spray formulation of cypermethrin may affect dung beetles
      differently than previously tested pour-on formulations. Following three beetle
      generations for two weeks each, the experiment retrieved no significant
      differences in adult or larval survival, egg production, fecundity and fertility
      between the control and treatment group. These results demonstrated that the used
      spray formulation of cypermethrin is likely to be far less detrimental to dung
      beetles than previously tested pour-ons.

PMID- 17201978
TI  - Detection and characterization of new genotypes of Myzus antirrhinii (Hemiptera:
      Aphididae) in Japan, with evidence for their production of sexual morphs.
AB  - Two forms of Myzus persicae (Sulzer), F-15 and R306N', resembling M. antirrhinii
      (Macchiati) in esterase profile have been found in Japan. To determine the
      genetic relationship of F-15 and R306N' with M. antirrhinii, clonal lineages of F
      15, R306N' and those of 14 other forms of M. persicae collected in Japan were
      analysed for 17 polymorphic microsatellite DNA loci. Two microsatellite multi
      locus (MS) genotypes of M. persicae and two MS genotypes, Ma3 and Ma4, of M.
      antirrhinii from Australia were used as references. The 16 Japanese forms were
      represented by different MS genotypes. F-15 and R306N' had, respectively, 44.1%
      and 35.3% of their alleles at the 17 loci in common with Ma3 and Ma4, and some of
      the common alleles were peculiar in size. F-15 and R306N' shared 22.6% and 29.6%,
      respectively, of their alleles with the other 16 MS genotypes of M. persicae. The
      corresponding values for Ma3 and Ma4 were both 27.4%. F-15 and R306N' were
      grouped reliably with the two Australian MS genotypes of M. antirrhinii both by
      neighbour-joining method based on shared allele distance and by a Bayesian method
      with Markov Chain Monte Carlo algorithm. These results suggest that F-15 and
      R306N' are genetically closely related to M. antirrhinii and isolated from the
      gene pool of M. persicae despite their ability to produce sexual morphs. It is
      therefore proposed that F-15 and R306N' should be classified as M. antirrhinii.

PMID- 17201976
TI  - The ecology of Helicoverpa spp. (Lepidoptera: Noctuidae) in the Riverina region
      of south-eastern Australia and the implications for tactical and strategic
      management.
AB  - Decisions on the choice of appropriate tactical and strategic control techniques
      require an understanding of the seasonal distribution and ecology of the target
      species. To address this need, data were collected from 1997 to 2000 using crop
      surveys, field sampling and pheromone trapping to monitor the population trends
      of Helicoverpa armigera (Hubner) and H. punctigera (Wallengren) in the Riverina
      region of south-eastern Australia. The data gathered are compared to predictions
      from the HElicoverpa Armigera and Punctigera Simulation (HEAPS) model, that
      simulates Helicoverpa population dynamics to assist in identifying the drivers of
      regional populations and provide a framework to make informed decisions. The
      results highlight the contrasting seasonal dynamics of H. punctigera and H.
      armigera within the region. Helicoverpa punctigera populations peak in the
      spring, driven by large scale spring migration into the region and subsequently
      decline. Helicoverpa armigera populations, conversely, are characterized by a
      period of spring recruitment of adults from overwintering pupae within the
      region, followed by a within-season population increase leading to severe late
      season pressure. The within-season increase of H. armigera is a result of the
      succession of crop and non-crop hosts with the main driver being sequentially
      sown, unsprayed maize. Tactical and strategic management options are discussed in
      light of these findings.

PMID- 17201979
TI  - Life history of Spodoptera exigua (Lepidoptera: Noctuidae) on various host
      plants.
AB  - The incubation period of Spodoptera exigua (Hubner) was not influenced by the
      host plant, whereas larval development time and pupal period were affected.
      Larval development time was longest on shallot and lady's finger, followed by
      cabbage and long bean. Larvae did not develop beyond the first instar when fed on
      chilli. The pupal period was longer on lady's finger than on cabbage, shallot and
      long bean. Overall, adult longevity was not influenced by the host plant but
      there was a difference between female and male longevity among the host plants.
      Survival of S. exigua was affected by the host plant at the larval stage. The
      number of larval instars varied between 5 and 8 within and between the studied
      host plants. Long bean was found to be the most suitable host plant and provide
      the best food quality for S. exigua compared to the other host plants, as it
      allowed faster development, fewer larval instars and a higher survival rate.

PMID- 17201980
TI  - Geographic biotype and host-associated local adaptation in a polyphagous species,
      Lambdina fiscellaria (Lepidoptera: Geometridae) feeding on balsam fir on
      Anticosti Island, Canada.
AB  - The debate about mechanisms underlying the evolution of host specialization by
      herbivorous insects remains open. Natural selection may act locally and lead to
      different patterns of geographic variation in life history traits of polyphagous
      herbivores. The hypothesis of genetically-based trade-offs in offspring
      performance on different hosts has been proposed but this has rarely been
      demonstrated. Under laboratory conditions, the biological performance of two
      populations of the hemlock looper Lambdina fiscellaria (Guenee), a highly
      polyphagous lepidopteran, was compared when reared on three different tree host
      species: balsam fir, eastern hemlock and sugar maple. One population originated
      from Anticosti Island, Quebec, Canada, where the insect has evolved without
      having access to two of the three tree species tested, the other being from the
      mainland where all tree species are present. When reared on balsam fir foliage,
      which was naturally available to each population, larvae from Anticosti Island
      underwent four instars compared with five for the mainland population, indicating
      the existence of geographic biotypes in L. fiscellaria. When reared on the
      foliage of non-naturally available host trees, larvae from Anticosti Island had a
      higher incidence of supernumerary instars. This is a unique example where local
      adaptation to environmental conditions of an insect herbivore is expressed
      through a differential number of larval instars. Moreover, the Anticosti Island
      population showed a higher growth related index on the host available to both
      populations indicating that a fitness trade-off was the evolutionary process
      underlying the local adaptation of this population on balsam fir.

PMID- 17201981
TI  - Habitat difference in abundance of willow leaf beetle Phratora vulgatissima
      (Coleoptera: Chrysomelidae): plant quality or natural enemies?
AB  - Herbivorous insects are influenced by both 'bottom-up' forces mediated through
      host plants and 'top-down' forces from natural enemies. Few studies have tried to
      evaluate the relative importance of the two forces in determining the abundance
      of insects. The leaf beetle Phratora vulgatissima Linnaeus sometimes occurs at
      high densities and severely damages the willow Salix cinerea in forest habitats.
      For willows growing in open agricultural landscapes (farmland S. cinerea), the
      leaf beetle generally occurs at low densities and plants receive little damage.
      The purpose of the present study was to evaluate the relative importance of host
      plant quality and natural enemies behind the observed difference in P.
      vulgatissima abundance. Female egg-laying and larval performance (growth and
      survival) were studied on caged willow branches in the field to investigate if
      plant quality differs between S. cinerea trees growing in forest and farmland
      habitats. The survival of eggs exposed to natural enemies was examined to see if
      predation could explain the low abundance of leaf beetles on farmland willows.
      The results indicated no difference in plant quality; female egg laying and
      larval performance did not differ between the forest and the farmland. However,
      heteropteran predators (true bugs) were more abundant, and the survival of eggs
      was lower, on plants in the farmland habitat than in the forest habitat. The data
      suggest that the low abundance of P. vulgatissima on farmland willows could not
      be explained by a poor quality of plants, but more likely by high predation from
      heteropterans.

PMID- 17201982
TI  - Biodiversity vs. biocontrol: positive and negative effects of alternative prey on
      control of slugs by carabid beetles.
AB  - Environment-friendly farming techniques seek to increase invertebrate
      biodiversity in part with the intention of encouraging greater numbers of
      predators that will help to control crop pests. However, in theory, this effect
      may be negated if the availability of a greater abundance and diversity of
      alternative prey diverts predators away from feeding on pests. The hypothesis
      that access to alternative prey can lead to reduced pest suppression under semi
      field conditions was tested. Alternative prey type and diversity were manipulated
      in 70 mesocosms over 7+ weeks in the presence of the carabid Pterostichus
      melanarius (Illiger), a known predator of slugs, and reproducing populations of
      the slug Deroceras reticulatum (Muller). Significantly fewer slugs survived where
      no alternative prey were provided. Maximum slug numbers and biomass were found in
      treatments containing either carabids plus a high diversity of alternative prey
      (many species of earthworm and three of Diptera larvae) or a single additional
      prey (blowfly larvae, Calliphora vomitoria Linnaeus). In these treatments slug
      numbers and biomass were as high as in plots lacking predators. The effects of
      alternative prey were taxon-specific. Alternative prey strongly affected carabid
      fitness in terms of biomass and egg load. The fittest predators (those with
      access to high alternative prey diversity or C. vomitoria larvae) reduced slug
      numbers the least. The mean individual slug weights were greater in treatments
      with alternative prey than where no alternative prey were provided to the
      carabids. These results suggest that pests may survive and reproduce more rapidly
      in patches where predators have access to alternative prey.

PMID- 17201983
TI  - Retroverted epiglottis presenting as a variant of globus pharyngeus.
AB  - We describe a series of four patients who presented with 'high globus
      pharyngeus', who all had an abnormally curled epiglottis tip touching and
      indenting the tongue base. The actual incidence of 'curling epiglottis', as well
      as the potential impact of this variation in persistent globus symptoms, is not
      known. We therefore describe for the first time a series of patients with this
      anatomical variant of the epiglottis, each of whom experienced unresolved globus
      symptoms despite receiving intensive medical treatment. In the literature, the
      success rate for improvement in symptoms following medical treatment ranges from
      68 to 80 per cent. Following CO2 laser partial epiglottectomy, all four patients
      experienced complete relief of their symptoms. We advocate consideration of this
      treatment for high globus pharyngeus that fails to respond to conservative
      treatment, in cases with proven curled epiglottis on endoscopic examination.

PMID- 17201984
TI  - Impact of sleep nasendoscopy on the outcome of mandibular advancement splint
      therapy in subjects with sleep-related breathing disorders.
AB  - AIM: To evaluate the impact of positive sleep nasendoscopy, with simultaneous
      mandibular advancement, on the outcome of mandibular advancement splint therapy
      in 120 subjects with sleep-related breathing disorders. METHODOLOGY: Overnight
      polysomnography and sleep nasendoscopy were performed prior to splint therapy.
      Follow-up sleep studies, with the appliance in situ, were undertaken for those
      patients with obstructive sleep apnoea. Subjective outcome measures assessed
      daytime sleepiness and snoring. RESULTS: One hundred and seven (89 per cent)
      subjects completed the study. Follow-up sleep studies confirmed the efficacy of
      treatment, with patients showing a mean reduction in apnoea/hypopnoea index (from
      18.9 to 4.9, p<0.001), Epworth sleepiness scale scores (from 11 to seven,
      p<0.001) and partner-recorded snoring scores (from 14 to eight, p<0.001).
      CONCLUSION: Sleep nasendoscopy, with concomitant mandibular advancement to mimic
      the treatment effect, could be of prognostic value in determining successful
      mandibular advancement splint therapy.

PMID- 17201985
TI  - Glial heterotopia of the middle ear.
AB  - A choristoma is the presence of histologically normal tissue in an area where it
      is not normally located. The most frequently reported choristoma of the middle
      ear is salivary choristoma. Heterotopic brain tissue is very uncommon in the
      middle ear and mastoid. We present a rare case of glial choristoma of the middle
      ear, together with a review of the literature.

PMID- 17201987
TI  - What is the severity of globus sensation in individuals who have never sought
      health care for it?
AB  - OBJECTIVES: To assess the pattern and severity of globus-type symptoms, as
      measured by the Glasgow Edinburgh throat scale, in individuals who had never
      sought health care for a feeling of something in the throat, in order to generate
      the first useful normative dataset for the Glasgow Edinburgh throat scale.
      METHODS: One hundred and seventy-four participants recruited from non-ENT clinics
      completed the Glasgow Edinburgh throat scale. They were distributed among three
      age groups (21-45, 46-65 and >65 years). RESULTS: The commonest throat symptoms
      reported were 'coughing to clear the throat', followed by 'catarrh down the
      throat' and 'discomfort/irritation in the throat'. CONCLUSIONS: The results of
      the study--a normative dataset for the Glasgow Edinburgh throat scale--may form
      the basis for: (a) the use of the Glasgow Edinburgh throat scale in primary care
      to identify patients for whom referral to secondary care may be appropriate; (b)
      monitoring the natural history of globus sensation; and (c) assessing response to
      intervention, in terms of resolution to baseline population levels of symptom
      severity.

PMID- 17201986
TI  - Role of three-dimensional computed tomography reconstruction in the management of
      elongated styloid process: a preliminary study.
AB  - Elongated styloid process is a relatively common cause of facial and neck pain,
      but it is often misdiagnosed due to its varied clinical presentation. Since an
      elongated styloid process is often confirmed by radiological means, it would be
      helpful to find a more accurate mode of depicting the styloid process. In this
      prospective study, 39 cases were evaluated. A three-dimensional computed
      tomography (3D CT) reconstruction of the styloid process was performed in 18
      cases. In these patients, we compared the length and medial angulation of the
      symptomatic styloid process as viewed on an orthopantomogram and a 3D CT
      reconstruction. It was noted that a 3D CT reconstruction was more accurate in
      depicting the styloid process. This investigation can be considered as the 'gold
      standard' in the radiological diagnosis of an elongated styloid process.

PMID- 17201988
TI  - Lemierre's--the sinister sore throat.
AB  - Lemierre's syndrome is a rare and sometimes life threatening condition that
      requires prompt management. A case is reported of a previously healthy young male
      with Lemierre's syndrome. He developed internal jugular vein and cavernous sinus
      thrombosis, metastatic abscesses in the temporal lobe and lungs, temporal lobe
      venous infarction and severe thrombocytopaenia. Discussed are aspects of clinical
      presentation, diagnosis and management issues.

PMID- 17201989
TI  - The choice of chromogen and reliability of contact rhinoscopy in the irradiated
      nasopharynx.
AB  - A cross-sectional randomised single blind study was conducted to assess how
      concentrations of chromogen (vital stain) and the characteristics of the
      assessors affect the assessment of contact rhinoscopy. Twenty-eight patients who
      had undergone external radiotherapy for nasopharyngeal carcinoma were assessed by
      contact rhinoscopy using 0.5 per cent and 1 per cent methylene blue stain on
      opposite sides of the nasopharynx. Three independent observers assessed the
      visual clarity of the 45 contact endoscopic images showing squamous metaplasia
      according to a visual analogue scale. The intraclass correlation coefficients
      were 0.916 to 0.957 and 0.839 to 0.964 for intra-observer reliability of
      assessors in the groups of 0.5 per cent and 1 per cent stains, respectively. The
      intraclass correlation coefficients for inter-observer reliability of assessors
      were 0.884 and 0.885 in the groups of 0.5 per cent and 1 per cent stains,
      respectively. The mean scores of clarity of the cellular details were
      statistically higher in the group of 1 per cent stain among all assessors. These
      results showed that the assessment of squamous metaplasia by contact endoscopy is
      highly reliable irrespective of the clinical experience and knowledge of
      histopathology of the assessors. One per cent methylene blue should be the vital
      stain of choice in contact endoscopy.

PMID- 17201990
TI  - A review of retraction pockets: past, present and future management.
AB  - Retraction pockets can lead to hearing loss and cholesteatoma. Distinguishing
      stable from progressive disease is challenging to any otologist. The management
      of retraction pockets is a contentious issue with present treatment options often
      plagued with recurrence. The purpose of this article is to summarize recent
      developments in the aetiology of retraction pockets of the pars tensa, its
      diagnostic and management problems and to define possible future therapeutic
      options.

PMID- 17201991
TI  - Endoscopic control of the sphenopalatine artery for epistaxis: long-term results.
AB  - The aim of this study was to prospectively evaluate post-operative cessation of
      bleeding and late recurrence of epistaxis in a cohort of patients treated by
      endoscopic ligation of the sphenopalatine artery. Participants comprised patients
      undergoing sphenopalatine artery ligation for posterior epistaxis at three east
      Scotland hospitals. Main outcome measures were recurrence of epistaxis in the
      immediate post-operative period and at long-term follow up (minimum nine months).
      Forty-three patients (30 men and 13 women) underwent 45 procedures; two patients
      underwent bilateral ligation. Two patients suffered recurrence as in-patients.
      Two patients experienced subsequent epistaxis requiring medical treatment. Two
      further patients suffered minor late epistaxis not requiring treatment. Success
      in preventing significant recurrence was 93 per cent. All recurrences requiring
      intervention occurred within one month of surgery. None of the patients in this
      series reported nasal complications. We found sphenopalatine artery ligation to
      be an effective means of achieving long-term control of posterior epistaxis.

PMID- 17201992
TI  - Responses of the entomopathogenic nematode, Steinernema riobrave to its insect
      hosts, Galleria mellonella and Tenebrio molitor.
AB  - Potential hosts for infective juveniles of entomopathogenic nematodes can vary
      considerably in quality based on the characteristics of the host species/stage,
      physiological status (e.g. stress, feeding on toxins), and infection status
      (heterospecific or conspecific infection). In this study, we investigated
      responses of the entomopathogenic nematode Steinernema riobrave to hosts
      (Galleria mellonella or Tenebrio molitor) that were previously parasitized with
      conspecifics or injected with the nematode-symbiotic bacterium, Xenorhabdus sp.,
      to determine if there is a preference for previously parasitized/injected hosts
      and when this preference might occur. In no-choice bioassays, the number of
      juveniles infecting both host species decreased with increasing time post
      infection. However, infective juveniles continued to infect previously
      parasitized hosts up to 72 h. Significant preference was exhibited by S. riobrave
      for 24 h post-infection G. mellonella larvae over uninfected, and by 24 h post
      injection G. mellonella larvae over 48 h post-injection larvae. No significant
      preference was exhibited by S. riobrave for T. molitor hosts previously
      parasitized with conspecifics or those injected with bacteria in any treatment
      combination. Such preference for, or continued infection of parasitized insects,
      has the potential to impact nematode efficacy.

PMID- 17201993
TI  - Subjective needs of people with dementia: a review of the literature.
AB  - OBJECTIVE: Insight into the individual care needs of the growing number of people
      with dementia is necessary to deliver more customized care. Our study aims to
      provide an overview of the literature on the subjective needs of people with
      dementia. METHOD: Electronic databases were searched for publications on
      subjective needs between January 1985 and July 2005, and reference lists were
      cross-referenced. Extracts of needs were classified within problem areas of the
      (Dutch) National Dementia Program and quality of life domains, and the extracts
      were classified as a "need" (an implicitly communicated felt state of
      deprivation), "want" (expression of a need) or "demand" (suitable solution to
      fulfill a need). RESULTS: Subjective needs were found in 34 studies with various
      research aims, such as awareness and coping. Few studies aimed to measure needs
      of people with dementia. The most frequently reported needs of people with
      dementia were the need to be accepted and respected as they are, the need to find
      adequate strategies to cope with disabilities, and the need to come to terms with
      their situation. Explicit wants or demands were reported less frequently than
      needs. CONCLUSION: The high number of reported needs and the limited number of
      wants and demands show that people with dementia do not frequently mention how
      they want their needs to be met. Most reported needs are not instrumental, but
      are related to well-being and coping. Further research to inventory these needs
      could help achieve more demand-directed and better attuned care in the future.

PMID- 17201994
TI  - Soluble cell adhesion molecules in late-life depression.
AB  - BACKGROUND: Late-life depression has been associated with vascular diseases and
      with increases in circulating cytokines and cell adhesion molecules in the
      prefrontal cortex. We hypothesized that soluble intercellular adhesion molecule-1
      (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) would be
      increased in late-life major depression. METHODS: Serum levels of sICAM-1 and
      sVCAM-1 were measured in subjects over 60 with major depression (N = 23),
      subsyndromal depression (N = 20) and controls (N = 25). Depression severity was
      assessed using the Montgomery-Asberg (MDRS) and Geriatric Depression (GDS) rating
      scales. RESULTS: There was no significant increase in sICAM-1 (p = 0.240) or
      sVCAM-1 (p = 0.600) in depression nor was there any correlation of either
      molecule with depression severity. Adjusting for differences in cognitive
      impairment did not alter these findings. There was also no difference between
      subjects with an early onset of depression (before 60) and those with late-onset
      depression. CONCLUSIONS: These findings do not provide evidence that previously
      reported increases in serum cytokines in depression are due to peripheral
      vascular disease. Although we assessed subjects for vascular diseases it is
      possible that subtle but important differences between groups may still have been
      present and may have contributed to our negative findings. Our results suggest
      central nervous system mechanisms, such as related to HPA axis activation, may be
      responsible for the enhanced inflammatory response in depression.

PMID- 17201995
TI  - Preparation of antidepressants for use in preclinical research.
AB  - Obtaining drugs for use in basic and preclinical research has become increasingly
      difficult and in many instances is dependent upon the company's interest in the
      proposed research. In this paper, we describe a simple procedure for extracting
      the antidepressants sertraline, paroxetine, fluoxetine, venlafaxine, citalopram,
      escitalopram, duloxetine and atomoxetine from their readily available
      pharmaceutical preparations. With the exception of citalopram, escitalopram and
      duloxetine in which the free base was the final product, the hydrochloride salt
      forms of these drugs were prepared. This procedure provides these antidepressants
      in gram quantities in recovered yields ranging from 53% to 100% at over 99%
      purity and is in principle applicable to other drugs as well.

PMID- 17201996
TI  - PET measurement of serotonin transporter occupancy: a comparison of escitalopram
      and citalopram.
AB  - The selective serotonin reuptake inhibitor (SSRI) citalopram (R,S-citalopram) is
      a racemic compound of two enantiomers. On the basis of in-vitro studies,
      inhibition of the human serotonin transporter (5-HTT) is achieved by the S
      enantiomer (S-citalopram or escitalopram). The aim of the present PET study was
      to compare 5-HTT occupancy after single equimolar doses (with respect to S
      enantiomer) in humans in vivo using R,S-citalopram (20 mg) and S-citalopram (10
      mg) using PET and the radioligand [(11)C]MADAM. The design was a single-dose,
      double-blind, two-way crossover study in eight healthy male subjects. The 5-HTT
      binding potential at baseline and after single doses of study drugs was used to
      calculate 5-HTT occupancy in seven brain regions. Serum concentrations of the
      study drugs were determined in order to calculate the apparent inhibition
      constant (K(i),(app)), a secondary parameter of interest for the comparison. In
      all brain regions examined, occupancy was numerically higher after treatment with
      R,S-citalopram [66+/-19% to 78+/-17% (mean+/-s.d.) depending on the region] than
      after S-citalopram (59+/-15% to 69+/-13%; overall comparison: F=14.8, d.f.=1, 90,
      p<0.001). In line with this the apparent inhibition constant was significantly
      lower for R,S-citalopram than for S-citalopram (overall comparison: F=6.7,
      d.f.=1, 90, p<0.05). The small but significant difference in occupancy and
      K(i),(app) found between R,S-citalopram and S-citalopram suggests that not only S
      citalopram but also R-citalopram to some degree occupies the 5-HTT in the human
      brain in vivo.

PMID- 17201997
TI  - RNA interference in parasitic helminths: current situation, potential pitfalls
      and future prospects.
AB  - RNA interference (RNAi) has become an invaluable tool for the functional analysis
      of genes in a wide variety of organisms including the free-living nematode
      Caenorhabditis elegans. Recently, attempts have been made to apply this
      technology to parasitic helminths of animals and plants with variable success.
      Gene knockdown has been reported for Schistosoma mansoni by soaking or
      electroporating different life-stages in dsRNA. Similar approaches have been
      tested on parasitic nematodes which clearly showed that, under certain
      conditions, it was possible to interfere with gene expression. However, despite
      these successes, the current utility of this technology in parasite research is
      questionable. First, problems have arisen with the specificity of RNAi. Treatment
      of the parasites with dsRNA resulted, in many cases, in non-specific effects.
      Second, the current RNAi methods have a limited efficiency and effects are
      sometimes difficult to reproduce. This was especially the case in strongylid
      parasites where only a small number of genes were susceptible to RNAi-mediated
      gene knockdown. The future application of RNAi in parasite functional genomics
      will greatly depend on how we can overcome these difficulties. Optimization of
      the dsRNA delivery methods and in vitro culture conditions will be the major
      challenges.

PMID- 17201998
TI  - Avian blood parasites in an endangered columbid: Leucocytozoon marchouxi in the
      Mauritian Pink Pigeon Columba mayeri.
AB  - There is increasing evidence that pathogens can play a significant role in
      species decline. This study of a complete free-living species reveals a cost of
      blood parasitism to an endangered host, the Pink Pigeon Columba mayeri, endemic
      to Mauritius. We investigated the prevalence and effect of infection of the blood
      parasite, Leucocytozoon marchouxi, in the free-living Pink Pigeon population.
      Overall, L. marchouxi infection prevalence detected was 18.3%. Juveniles were
      more likely to be infected than older birds and there was geographical variation
      in infection prevalence. Survival of birds infected with L. marchouxi was lower
      than that of uninfected birds to 90 days post-sampling. This study suggests that
      while common haematozoa are well tolerated in healthy adults, these parasites may
      have greater pathogenic potential in susceptible juveniles. The study is unusual
      given its completeness of species sampling (96%) within a short time-period, the
      accurate host age data, and its focus on blood parasites in a threatened bird
      species. Species for which long-term life-history data are available for every
      individual serve as valuable models for dissecting the contribution of particular
      pathogens to species decline.

PMID- 17202000
TI  - Risk of schizophrenia in second-generation immigrants: a Danish population-based
      cohort study.
AB  - BACKGROUND: Urban birth, a risk factor for schizophrenia, is more frequent among
      second-generation immigrants. The aim of the current study was to determine
      whether the increased risk for schizophrenia found in second-generation
      immigrants is explained by the degree of urbanization of birthplace and/or
      factors related to parentage, such as geographic origin or history of residence
      abroad during upbringing. METHOD: Using data from the Danish Civil Registration
      System (CRS), we established a population-based cohort of 2.0 million Danes
      (persons born in Denmark). Schizophrenia in cohort members was identified by
      cross-linkage with the Danish Psychiatric Central Register. RESULTS: The relative
      risk of developing schizophrenia was 1.93 [95% confidence interval (CI) 1.79
      2.08] and 2.96 (95% CI 2.49-3.51) among persons with one or both parents foreign
      born respectively compared to native Danes. Adjustment for urbanization of
      birthplace and parental characteristics reduced these risks slightly. However,
      urbanization had a lesser effect in second-generation immigrants than in Danes.
      History of residence abroad was a risk factor for schizophrenia, regardless of
      whether parents were foreign-born or native Danes. CONCLUSION: The increased risk
      found in second-generation immigrants cannot be explained by urbanization or
      parental characteristics pertaining to age, mental illness, geographic origin or
      residence abroad during a child's upbringing.

PMID- 17201999
TI  - Generalized anxiety disorder and depression: childhood risk factors in a birth
      cohort followed to age 32.
AB  - BACKGROUND: The close association between generalized anxiety disorder (GAD) and
      major depressive disorder (MDD) prompts questions about how to characterize them
      in future diagnostic systems. We tested whether risk factors for MDD and GAD are
      similar or different. METHOD: The representative 1972-73 Dunedin birth cohort of
      1037 males and females was followed to age 32 with 96% retention. Adult GAD and
      MDD were diagnosed at ages 18, 21, 26, and 32 years, and juvenile
      anxiety/depression were also taken into account. Thirteen prospective risk
      measures indexed domains of family history, adverse family environment, childhood
      behavior, and adolescent self-esteem and personality traits. RESULTS: Co-morbid
      MDD+GAD was antedated by highly elevated risk factors broadly across all domains.
      MDD+GAD was further characterized by the earliest onset, most recurrence, and
      greatest use of mental health services and medication. Pure GAD had levels of
      risk factors similar to the elevated levels for co-morbid MDD+GAD; generally,
      pure MDD did not. Pure GAD had risks during childhood not shared by pure MDD, in
      domains of adverse family environment (low SES, somewhat more maltreatment) and
      childhood behavior (internalizing problems, conduct problems, somewhat more
      inhibited temperament). Pure MDD had risks not shared by pure GAD, in domains of
      family history (of depression) and personality (low positive emotionality).
      CONCLUSIONS: Specific antecedent risk factors for pure adult MDD versus GAD may
      suggest partly different etiological pathways. That GAD and co-morbid MDD+GAD
      share many risk markers suggests that the presence of GAD may signal a pathway
      toward relatively more severe internalizing disorder.

PMID- 17202001
TI  - Can we predict suicide and non-fatal self-harm with the Beck Hopelessness Scale?
      A meta-analysis.
AB  - BACKGROUND: Hopelessness is considered a pre-eminent risk factor for suicide and
      non-fatal self-harm. We aimed to quantify the ability of the Beck Hopelessness
      Scale (BHS) to predict these two outcomes. METHOD: Medline, Embase, PsycINFO and
      Cinahl were searched to January 2006. We included cohort studies in which the BHS
      was applied and patients were followed-up to establish subsequent suicide or non
      fatal self-harm. Four studies provided usable data on suicide, and six studies
      provided data on non-fatal self-harm. Summary sensitivity, specificity,
      likelihood ratios and diagnostic odds ratios (DORs) were calculated for each
      study. Random effects meta-analytic pooling across studies at the standard cut
      off point (> or =9) was undertaken and summary receiver operating characteristic
      (ROC) curves constructed. RESULTS: For suicide, pooled sensitivity was 0.80 [95%
      confidence interval (CI) 0.68-0.90], pooled specificity was 0.42 (95% CI 0.41
      0.44), and the pooled DOR was 3.39 (95% CI 1.29-8.88). For non-fatal self-harm,
      pooled sensitivity was 0.78 (95% CI 0.74-0.82), pooled specificity was 0.42 (95%
      CI 0.38-0.45), and the pooled DOR was 2.27 (95% CI 1.53-3.37). CONCLUSION: The
      standard cut-off point on the BHS identifies a high-risk group for potential
      suicide, but the magnitude of the risk is lower than previously reported
      estimates. The standard cut-off point is also capable of identifying those who
      are at risk of future self-harm, but the low specificity rate means it is
      unlikely to be of use in targeting treatment designed to lower the rate of
      repetition.

PMID- 17202002
TI  - Income-related inequality in mental health in Britain: the concentration index
      approach.
AB  - BACKGROUND: Reduction of health inequalities is a major policy goal in the UK.
      While there is general recognition of the disadvantaged position of people with
      mental health problems, the extent of inequality, particularly the association
      with socio-economic characteristics, has not been widely studied. We aimed to
      measure income-related inequality in the distribution of psychiatric disorders
      and to compare with inequality in other health domains. METHOD: The concentration
      index (CI) approach was used to examine income-related inequality in mental
      health using data from the Psychiatric Morbidity Survey 2000 for Britain.
      RESULTS: There is marked inequality unfavourable to lower income groups with
      respect to mental health disorders. The extent of inequality increases with the
      severity of problems, with the greatest inequality observed for psychosis. Income
      related inequality for psychiatric disorders is higher than for general health in
      the UK. Standardized CIs suggest that these inequalities are not due to the
      demographic composition of the income quintiles. CONCLUSIONS: Income-related
      inequalities exist in mental health in Britain. As much of the observed
      inequality is probably due to factors associated with income and not due to the
      demographic composition of the income quintiles, it may be that these
      inequalities are potentially 'avoidable'.

PMID- 17202003
TI  - Testing the self-medication hypothesis of depression and aggression in cannabis
      dependent subjects.
AB  - BACKGROUND: A self-medication hypothesis has been proposed to explain the
      association between cannabis use and psychiatric and behavioral problems.
      However, little is known about the reasons for use and reactions while
      intoxicated in cannabis users who suffer from depression or problems controlling
      violent behavior. METHOD: We assessed 119 cannabis-dependent subjects using the
      Schedules of Clinical Assessment in Neuropsychiatry (SCAN), parts of the
      Addiction Severity Index (ASI), and questionnaires on reasons for cannabis use
      and reactions to cannabis use while intoxicated. Participants with lifetime
      depression and problems controlling violent behavior were compared to subjects
      without such problems. Validity of the groupings was corroborated by use of a
      psychiatric treatment register, previous use of psychotropic medication and
      convictions for violence. RESULTS: Subjects with lifetime depression used
      cannabis for the same reasons as others. While under the influence of cannabis,
      they more often experienced depression, sadness, anxiety and paranoia, and they
      were less likely to report happiness or euphoria. Participants reporting problems
      controlling violent behavior more often used cannabis to decrease aggression,
      decrease suspiciousness, and for relaxation; while intoxicated they more often
      reacted with aggression. CONCLUSIONS: Subjects with prior depression do not use
      cannabis as a mean of self-medication. They are more likely to experience
      specific increases of adverse symptoms while under the influence of cannabis, and
      are less likely to experience specific symptom relief. There is some evidence
      that cannabis is used as a means of self-medication for problems controlling
      aggression.

PMID- 17202004
TI  - Predicting costs of mental health care: a critical literature review.
AB  - BACKGROUND: Cost evaluation research in the mental health field is being
      increasingly recognized as a way to achieve a more effective deployment of scarce
      resources. However, there is a paucity of studies that seek to identify
      predictors of psychiatric service utilization and costs. This paper aims to
      critically review the published research in the field of psychiatric service
      utilization and costs, and discusses current methodological developments in this
      field. METHOD: Sixteen studies were identified and are critically reviewed.
      RESULTS: No single variable alone can explain variations in costs between
      patients; instead, a range of different clinical and non-clinical variables
      provides a greater explanation of cost variations. Having a history of previous
      psychiatric service use is the most consistent predictor of higher psychiatric
      costs. Only one study considers indirect costs incurred by users, their families
      and friends and society as a whole, with the remaining 15 studies focusing on
      direct mental health care costs. There is a lack of studies that consider the
      future psychiatric service utilization and costs of care of children and older
      people. The cross-validation of predictive models is not yet routine, with only
      four of the studies including a cross-validation procedure. CONCLUSIONS: The
      predictive approach in mental health cost evaluation has relevance for both
      mental health policy and practice. However, there is a paucity of studies that
      focus on children, older people and indirect costs. Furthermore, there remain a
      number of methodological challenges to address.

PMID- 17202005
TI  - State affective instability in borderline personality disorder assessed by
      ambulatory monitoring.
AB  - BACKGROUND: Although affective instability is an essential criterion for
      borderline personality disorder (BPD), it has rarely been reported as an outcome
      criterion. To date, most of the studies assessing state affective instability in
      BPD using paper-pencil diaries did not find indications of this characteristic,
      whereas in others studies, the findings were conflicting. Furthermore, the
      pattern of instability that characterizes BPD has not yet been identified.
      METHOD: We assessed the affective states of 50 female patients with BPD and 50
      female healthy controls (HC) during 24 hours of their everyday life using
      electronic diaries. RESULTS: In contrast to previous paper-and-pencil diary
      studies, heightened affective instability for both emotional valence and distress
      was clearly exhibited in the BPD group but not in the HC group. Inconsistencies
      in previous papers can be explained by the methods used to calculate instability
      (see Appendix). In additional, we were able to identify a group-specific pattern
      of instability in the BPD group characterized by sudden large decreases from
      positive mood states. Furthermore, 48% of the declines from a very positive mood
      state in BPD were so large that they reached a negative mood state. This was the
      case in only 9% of the HC group, suggesting that BPD patients, on average, take
      less time to fluctuate from a very positive mood state to a negative mood state.
      CONCLUSION: Future ambulatory monitoring studies will be useful in clarifying
      which events lead to the reported, sudden decrease in positive mood in BPD
      patients.

PMID- 17202006
TI  - Perioperative management of familial dysautonomia: a systematic review.
AB  - BACKGROUND AND OBJECTIVE: Familial dysautonomia (FD), a rare genetic disorder, is
      characterized by autonomic instability, pulmonary infections, oesophageal
      dysmotility, spinal abnormalities and episodic "dysautonomic crisis"
      characterized by rash, vomiting, sweating and hypertension. Frequent anaesthetic
      complications have been reported. METHODS: We performed a comprehensive
      literature search of perioperative management of FD using an OVID-based search
      strategy. Identified reports were reviewed to identify perioperative
      complications as well as anaesthetic techniques and perioperative management
      strategies developed to minimize or prevent these complications. RESULTS:
      Eighteen case reports or series of perioperative management of FD were identified
      in the literature for a total of 179 patients undergoing 290 anaesthetics.
      Intraoperative cardiovascular lability, including cardiac arrests and
      postoperative pulmonary complications were commonly reported. Preoperative
      hydration, minimizing the use of volatile anaesthetic agents, postoperative
      ventilation, use of regional anaesthesia and minimally invasive surgical
      techniques reduced the incidence of these complications. CONCLUSIONS: While
      patients with FD are reported to have a relatively high rate of various
      perioperative complications, a full understanding of its pathophysiology can be
      used to develop a perioperative management strategy to anticipate and prevent
      many of these complications.

PMID- 17202008
TI  - Comparison of diphenhydramine and lidocaine for prevention of pain after
      injection of propofol: a double-blind, placebo-controlled, randomized study.
AB  - BACKGROUND AND OBJECTIVE: Pain on injection is still a problem with propofol. The
      purpose of the study was to compare the effectiveness of diphenhydramine and
      lidocaine on pain caused by propofol at the site of injection. METHODS: One
      hundred and eighty ASA I-II adults undergoing elective surgery were randomly
      assigned into three groups of 60 each. Group I (placebo) received 2 mL normal
      saline, Group II received 2 mL (40 mg) 2% lidocaine and Group III received 2 mL
      (20 mg) diphenhydramine intravenously (i.v.) during a 1-min venous occlusion,
      followed by propofol into a cephalic forearm vein of the antecubital fossa. Pain
      assessment was made immediately after propofol injection. RESULTS: In the placebo
      group 25 (41.7%) patients experienced pain during propofol injection as compared
      to 2 (3.3%) and 3 (5.0%) in the lidocaine and diphenhydramine groups,
      respectively. The prevalence of pain and pain score were significantly less in
      both the lidocaine and diphenhydramine groups than in the placebo group (P =
      0.00). No difference was found between the diphenhydramine and lidocaine groups
      (P = 0.60). CONCLUSION: Previous injection of diphenhydramine with venous
      occlusion can be considered as an alternative to lidocaine for reducing the
      prevalence of pain caused by injection of propofol into peripheral veins.

PMID- 17202007
TI  - Levobupivacaine 0.75% vs. lidocaine 4% for topical anaesthesia: a clinical
      comparison in cataract surgery.
AB  - BACKGROUND: The aim of this study was to compare the efficacy of topical
      levobupivacaine drops 0.75% vs. lidocaine drops 4% in cataract surgery. METHODS:
      We examined 203 patients undergoing cataract surgery by phacoemulsification. They
      were randomized into two groups: one received four drops of lidocaine 4% and the
      other received four drops of levobupivacaine 0.75%. The onset and offset times of
      sensory block were evaluated. Application, intraoperative and postoperative
      subjective pain was quantified by the patients using a verbal pain score.
      Complications, rates of supplemental anaesthesia, and the satisfaction of surgeon
      and patients were also recorded. RESULTS: The mean sensory onset and offset times
      were significantly higher for the levobupivacaine group (P < 0.01). Pain score
      was lower in the levobupivacaine group than in the lidocaine one and the
      difference was statistically significant at all stages (P < 0.01). The mean
      satisfaction scores of patients and surgeon were also statistically higher for
      levobupivacaine (P < 0.01). No significant differences for complications and
      rates of supplemental anaesthesia were found. CONCLUSIONS: Topical
      levobupivacaine 0.75% shows the same efficacy and safety as lidocaine 4% in
      cataract surgery by phacoemulsification. There was an adequate block with a good
      level of satisfaction of surgeon and patients. Levobupivacaine 0.75% offers a new
      and acceptable choice for topical anaesthesia in cataract surgery.

PMID- 17202009
TI  - Recovery of older patients undergoing ambulatory anaesthesia with isoflurane or
      sevoflurane.
AB  - BACKGROUND: Delayed recovery of cognitive function is a well-recognized
      phenomenon in older patients. The potential for the volatile anaesthetic used to
      contribute to alterations in postoperative cognitive function in older patients
      following minor surgical procedures has not been determined. We compared
      emergence from isoflurane and sevoflurane anaesthesia in older surgical patients
      undergoing urological procedures of short duration. METHODS: Seventy-one
      patients, 60 yr of age or older, undergoing anaesthesia expected to last less
      than 60 min for ambulatory surgery, were randomly assigned to receive isoflurane
      or sevoflurane. A standardized anaesthetic protocol was used, with intravenous
      fentanyl 1 microg kg(-1) and propofol 1.5-2.0 mg kg(-1) administered to induce
      anaesthesia. Anaesthesia was maintained with either sevoflurane or isoflurane in
      65% nitrous oxide and oxygen. Early and intermediate recovery times were
      recorded. The Mini Mental State Examination and digit repetition forwards and
      backwards were administered at baseline, and at 1, 3 and 6 h postoperatively, to
      assess cognitive function. RESULTS: There were no between-group differences in
      (sevoflurane vs. isoflurane, mean +/- standard error of the mean) times to
      removal of the laryngeal mask airway (7.7 +/- 0.6 vs. 7.1 +/- 0.4 min), verbal
      response time (10.1 +/- 0.7 vs. 9.9 +/- 0.7 min) and orientation (12.1 +/- 0.7
      vs. 12.1 +/- 0.7 min). Intermediate recovery, as measured by time to readiness
      for discharge from the post anaesthesia care unit (44.9 +/- 1.5 vs. 44.3 +/- 1.5
      min), was similar in the two groups. Postoperative indices of cognitive function
      and attention were comparably reduced at 1 h, but returned to baseline in both
      groups at 6 h. CONCLUSIONS: Isoflurane and sevoflurane anaesthesia resulted in
      similar clinical and neurocognitive recovery profiles in older patients
      undergoing ambulatory surgical procedures of short duration.

PMID- 17202011
TI  - Fatal endotracheal haemorrhage in a patient undergoing repair of a large
      ascending aortic aneurysm.

PMID- 17202010
TI  - Preoperative oral dextromethorphan vs. clonidine to prevent tourniquet-induced
      cardiovascular responses in orthopaedic patients under general anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: Preoperative oral dextromethorphan and intravenous
      clonidine attenuate arterial pressure and heart rate increases during tourniquet
      inflation under general anaesthesia. The effect of preoperative oral clonidine on
      these variables has not been investigated. METHODS: We designed this study to
      compare the effect of preoperative oral dextromethorphan or clonidine on
      haemodynamic changes during tourniquet inflation in 75 patients undergoing lower
      limb surgery under general anaesthesia. Patients were randomly assigned into
      three groups: dextromethorphan 30 mg (n = 25), clonidine 3 microg kg(-1) (n = 25)
      and placebo (n = 25). Anaesthesia was maintained with isoflurane 1.2% and N2O 50%
      in oxygen with endotracheal intubation. Dextromethorphan, clonidine or placebo
      was given orally in a double-blinded fashion 90 min before induction of
      anaesthesia. Systolic, diastolic and mean arterial pressure and heart rate were
      measured at 0, 30, 45, 60 min after the start of tourniquet inflation, before
      tourniquet release and 20 min after tourniquet deflation. RESULTS: Systolic,
      diastolic and mean arterial pressure were significantly lower in the clonidine
      group compared with control after 45, 60 min tourniquet inflation and before
      tourniquet release (P < 0.05). Twenty minutes after deflation, diastolic and mean
      arterial pressure in the control group were still increased and significantly
      higher compared with the clonidine group (P < 0.05). Development of more than a
      30% increase in systolic arterial pressure during tourniquet inflation was more
      frequent in the control group than in the other groups. CONCLUSIONS: Preoperative
      oral clonidine 3 microg kg(-1) significantly prevented tourniquet-induced
      systemic arterial pressure increase in patients under general anaesthesia better
      than oral dextromethorphan.

PMID- 17202013
TI  - Comparison of the GlideScope video laryngoscope vs. the intubating laryngeal mask
      for females with normal airways.
AB  - BACKGROUND AND OBJECTIVE: In this randomized clinical study, we compared the
      intubation success rates of the intubating laryngeal mask airway with the
      GlideScope in patients with normal airways. The primary hypothesis was that the
      intubating laryngeal mask airway was equally effective as the GlideScope in terms
      of successful intubation times. METHODS: Sixty ASA I and II adult patients
      undergoing elective gynaecological surgery were randomly allocated into either
      the intubating laryngeal mask airway group or the GlideScope group. After a
      standard anaesthetic intravenous induction, orotracheal intubation was performed.
      Time taken for successful tracheal intubation, ease of device insertion,
      difficulty of tracheal intubation, manoeuvres needed to aid tracheal intubation,
      number of intubation attempts, haemodynamic changes every 2.5 min interval for 5
      min and complications during tracheal intubation were recorded. RESULTS: Time to
      successful intubation was longer (mean 68.4 s +/- 23.5 vs. 35.7 s +/- 10.7; P <
      0.05), mean difficulty score was higher (mean 16.7 +/- 16.3 vs. 7.3 +/- 13.1; P <
      0.05) and more intubation attempts were required in the intubating laryngeal mask
      airway group. CONCLUSION: The GlideScope improved intubation time and difficulty
      score for tracheal intubation when compared with the intubating laryngeal mask
      airway in our patients. Blind intubation through the intubating laryngeal mask
      airway offers no advantages over the GlideScope in patients with normal airways.
      Despite its limitations, the intubating laryngeal mask airway is a valuable
      adjunct, especially in cases of difficult airway management when it can provide
      ventilation in between intubation attempts.

PMID- 17202012
TI  - Ephedrine, phenylephrine and BIS during propofol anaesthesia.

PMID- 17202014
TI  - Effects of preload alterations on peak early diastolic mitral annulus velocities
      evaluated by tissue Doppler echocardiography.
AB  - BACKGROUND AND OBJECTIVE: Tissue Doppler echocardiography is proposed to be a
      relatively preload independent tool for assessment of diastolic function. No data
      exist on anaesthetized patients in whom myocardial contractility, vascular tone
      and baroreceptor reflexes are depressed. The aim of this study was to evaluate
      the effects of preload alterations on tissue velocities in patients during
      general anaesthesia for coronary arterial bypass surgery. METHODS: Fifteen
      patients referred for elective aorto-coronary bypass surgery were examined by
      tissue Doppler echocardiography. Early diastolic velocities in the septal and
      lateral portion of the mitral annulus were measured during preload interventions
      induced by tilting of the operating table in patients during general anaesthesia
      both before surgery and after chest closure. To verify changes in preload we used
      right atrial pressure and pulmonary artery occlusion pressure. RESULTS: Tissue
      velocities in both the septal and lateral portion of the mitral annulus were
      significantly higher when preload was increased, compared to when it was
      decreased. Alterations in diastolic velocities in the septal portion of the
      mitral annulus prior to surgery: 0.8 +/- 0.2 cm s-1, P < 0.001, after surgery:
      1.1 +/- 0.2 cm s-1, P < 0.001. Alterations in diastolic velocities in the lateral
      portion of the mitral annulus prior to surgery: 1.4 +/- 0.2 cm s-1, P < 0.001,
      after surgery: 1.1 +/- 0.3 cm s-1, P < 0.01. Concomitant changes in right atrial
      pressure and pulmonary artery occlusion pressure were 11 +/- 1 and 12 +/- 1 mmHg
      before surgery and 13 +/- 1 and 12 +/- 1 mmHg after surgery (P < 0.001 for all),
      respectively. CONCLUSION: These results show that tissue velocities of the mitral
      annulus are preload dependent in patients during general anaesthesia both before
      and after coronary surgery.

PMID- 17202020
TI  - [Regulating radiological protection and the role of health authorities].
AB  - This article summarizes the development of protection against ionizing radiation
      and explains current thinking in the field. It also looks at the decisive role
      that regulatory agencies for radiological protection must play and the important
      contributions that can be made by health authorities. The latter should take an
      active part in at least three aspects: the formal education of health personnel
      regarding radiological protection; the medical care of individuals who are
      accidentally overexposed, and the radiological protection of patients undergoing
      radiological procedures. To this end, health professionals must possess
      sufficient knowledge about radiological protection, promote the use of proper
      equipment, and apply the necessary quality assurance procedures. Through their
      effective intervention, national health authorities can greatly contribute to
      reducing unnecessary doses of radiation during medical procedures involving
      radiation sources and decrease the chances that radiological accidents will take
      place.

PMID- 17202022
TI  - Objective and subjective evaluation of the acoustic comfort in classrooms.
AB  - The acoustic comfort of classrooms in a Brazilian public school has been
      evaluated through interviews with 62 teachers and 464 pupils, measurements of
      background noise, reverberation time, and sound insulation. Acoustic measurements
      have revealed the poor acoustic quality of the classrooms. Results have shown
      that teachers and pupils consider the noise generated and the voice of the
      teacher in neighboring classrooms as the main sources of annoyance inside the
      classroom. Acoustic simulations resulted in the suggestion of placement of
      perforated plywood on the ceiling, for reduction in reverberation time and
      increase in the acoustic comfort of the classrooms.

PMID- 17202023
TI  - The basal ganglia: an overview of circuits and function.
AB  - The technique of electrical stimulation of brain tissue-known clinically as deep
      brain stimulation (DBS)-is at the fore of treatment of human neurological
      disease. Here we provide a general overview highlighting the anatomy and
      circuitry of the basal ganglia (BG). We introduce common disease states
      associated with BG dysfunction and current hypotheses of BG function. Throughout
      this introductory review we direct the reader to other reviews in this special
      issue of Neuroscience and Biobehavioral Reviews highlighting the interaction
      between basic science and clinical investigation to more fully understand the BG
      in both health and disease.

PMID- 17202024
TI  - Treating asthma with a self-management model of illness behaviour in an
      Australian community pharmacy setting.
AB  - Asthma affects a considerable proportion of the population worldwide and presents
      a significant health problem in Australia. Given its chronic nature, effective
      asthma self-management approaches are important. However, despite research and
      interventions targeting its treatment, the management of asthma remains
      problematic. This study aimed to develop, from a theoretical basis, an asthma
      self-management model and implement it in an Australian community pharmacy
      setting in metropolitan Sydney, using a controlled, parallel-groups repeated
      measures design. Trained pharmacists delivered a structured, step-wise, patient
      focused asthma self-management program to adult participants over a 9-month
      period focusing on identification of asthma problems, goal setting and strategy
      development. Data on process- clinical- and psychosocial-outcome measures were
      gathered. Results showed that participants set an average of four new goals and
      six repeated goals over the course of the intervention. Most common goal-related
      themes included asthma triggers, asthma control and medications. An average of
      nine strategies per participant was developed to achieve the set goals. Common
      strategies involved visiting a medical practitioner for review of medications,
      improving adherence to medications and using medications before exercise.
      Clinical and psychosocial outcomes indicated significant improvements over time
      in asthma symptom control, asthma-related self-efficacy and quality of life, and
      negative affect. These results suggest that an asthma self-management model of
      illness behaviour has the potential to provide patients with a range of process
      skills for self-management, and deliver improvements in clinical and psychosocial
      indicators of asthma control. The results also indicate the capacity for the
      effective delivery of such an intervention by pharmacists in Australian community
      pharmacy settings.

PMID- 17202025
TI  - Social capital, trust in the health-care system and self-rated health: the role
      of access to health care in a population-based study.
AB  - This paper investigates the relationship between institutional trust in the
      health-care system, i.e. an institutional aspect of social capital, and self
      rated health, and whether the strength of this association is affected by access
      to health-care services. The 2004 public health survey in the Scania region of
      Sweden is a cross-sectional study; a total of 27,963 respondents aged 18-80 years
      answered a postal questionnaire, which represents 59% of the random sample.
      Logistic regression model was used to investigate the association between
      institutional trust and self-rated health. Multivariate analyses of self-rated
      health were performed in order to investigate the importance of possible
      confounders (age, country of origin, education, economic stress, generalized
      trust in other people, and care-seeking behaviour) on this association. A 28.7%
      proportion of the men and 33.2% of the women reported poor self-rated health. A
      total of 15.0% and 58.3% of the respondents reported "very high" and "rather
      high" trust in the health-care system, respectively. Almost one-third of all
      respondents reported low institutional trust. Respondents born outside Sweden,
      with low/medium education, low generalized trust and low institutional trust had
      significantly higher odds ratios of poor self-rated health. Multiple adjustments
      for age, country of origin, education, economic stress, and horizontal trust had
      some effect on the significant relationship between institutional trust and poor
      self-rated health, for both men and women, but the additional introduction of
      care-seeking behaviour in the model substantially reduced the odds ratios. In
      conclusion, low trust in the health-care system is associated with poor self
      rated health. This association may be partly mediated by "not seeking health care
      when needed". However, this is a cross-sectional exploratory study and the
      causality may go in both directions.

PMID- 17202026
TI  - Nanoparticles in wastewater from a science-based industrial park - coagulation
      using polyaluminum chloride.
AB  - The Hsinchu Science-based Industrial Park (HSIP) is the hi-tech manufacturing hub
      of Taiwan. Wastewater from the HSIP contains numerous nano-sized silicate
      particles whose size distributions peak at 2 and 90 nm. A 3-5 mg l(-1) as Al dose
      of polyaluminum chloride (PACl) was used in the field to coagulate these
      particles, but the removal efficiency was low. Laboratory scale tests indicated
      that although PACl coagulation removed 52% of the turbidity and 48% of the
      chemical oxygen demand (COD) from water, its effect on nano-particle removal was
      minimal. About 58% of the soluble COD was associated with colloidal Si particles.
      A light scattering test and transmission electron microscopy (TEM) demonstrated
      that the nano-particles agglomerated in approximately linear aggregates of sizes
      100-300 nm. Prolonged contact between residual PACl and the nano-particles
      generated large aggregates with sizes of up to 10 microm and a fractal dimension
      of 2.24-2.63. The results presented herein should be of interest in the
      processing of "high-tech" wastewater that contains nanosized silica particles.

PMID- 17202027
TI  - The effects of sediment-laden waters on irrigated lands along the lower Yellow
      River in China.
AB  - Expansion of irrigation in the Yellow River (Huang He in Chinese) Basin of China
      is a major accomplishment of the post-revolutionary period in China. Irrigation
      reliance on the Yellow River was anticipated to not only supply greater
      reliability of water for crops, but also to improve the productivity of aeolian,
      saline and alkali soils because of the high sediment loads in the river.
      Irrigation expansion also was a significant factor in affecting human
      modification of the landscape ecosystem in the lower reaches of the Yellow River.
      Based on field investigation and sampling of the amount and distribution of used
      suspended sediment load in irrigated areas, this paper analyzes the impact of the
      suspended sediment on soil texture, fertility and salinity and the consequences
      to the landscape ecosystem. Results indicate that soil quality has indeed been
      improved through irrigation and related deposition of sediment, but some local
      problems created by long periods of irrigation should not be ignored in the
      future.

PMID- 17202028
TI  - Agronomic application of olive mill wastewaters with phosphate rock in a semi
      arid Mediterranean soil modifies the soil properties and decreases the
      extractable soil phosphorus.
AB  - Olive mill wastewater (OMW), a by-product of the olive-mill industry, is produced
      in large amounts in Mediterranean countries. The presence of indigenous phosphate
      deposits in some countries like Tunisia provides an incentive for direct
      application or local chemical treatment at low cost to improve the solubility of
      low reactive phosphate rocks (PRs). The use of naturally occurring low-molecular
      weight organic acids (LMWOAs) that are present in OMW represents a new
      perspective in PR research and a possible solution for the recycling of the OMW.
      The present work was aimed at evaluating, under natural situations (field of
      olive trees), the effects of agronomic application of OMW (amounts applied: 30,
      60 m(3) ha(-1)) with PR (amounts applied: 150 kg ha(-1)) on olive trees soil
      properties. We measured organic C, nitrogen (N), extractable phosphorus (P),
      exchangeable calcium (Ca), and exchangeable potassium (K), as well as other
      properties (pH and electrical conductivity). Our data provide evidence that
      agronomic application of OMW with PR has important effects on soil properties.
      Increases in organic C, total N, extractable P and exchangeable potassium (K)
      were found after the first agronomic application of OMW and PR. These increases
      were only temporary, following the second agronomic application of OMW and PR,
      significant reductions were detected in the extractable soil P (19.67 mg kg(-1)
      in the control soil vs. 8.99 mg kg(-1) in the amended soil). Changes in the
      extractable soil P could alter plant productivity and plant community structure
      because shifts in nutriment availability can affect the balance between limiting
      and non-limiting nutrients.

PMID- 17202029
TI  - Quantification of the regional carbon cycle of the biosphere: policy, science and
      land-use decisions.
AB  - This paper addresses some issues related to the carbon cycle and its utilization
      by society. Traditional uses for agriculture, forestry, as a source of fuel and
      other products, and for pastoral farming, among others, have recently been
      supplemented by identifying its potential for mitigating the increasing
      concentration of greenhouse gases in the atmosphere. Through the Kyoto Protocol,
      carbon has become a commodity and the CO(2)-absorbing capability of the
      vegetation and soils an economically valuable asset. The multi-facetted roles of
      the C cycle and its sensitivity to human activities present a demand for
      techniques that permit accurate, timely and affordable characterization of the
      various components of this cycle, especially on land where most human activities
      take place. Such techniques must satisfy a range of demands in terms of purpose,
      clients for the information, and biosphere properties. However, if successful,
      they offer the potential to support monitoring, reporting, policy setting, and
      management of terrestrial biospheric resources. The context for these
      requirements and possibilities is illustrated with reference to the China Carbon
      Sequestration Project and its findings.

PMID- 17202030
TI  - Amphileptus aeschtae nov. spec. and Amphileptus eigneri nov. spec. (Ciliophora,
      Pleurostomatida), two new marine pleurostomatid ciliates from China.
AB  - The morphology and infraciliature of two pleurostomatid ciliates, Amphileptus
      aeschtae nov. spec. and Amphileptus eigneri nov. spec., collected from shrimp
      culturing ponds of the Bohai Sea, China, were investigated using live
      observations and the protargol impregnation method. The new species A. aeschtae
      is identified by the presence of 200-300 macronuclear nodules and several
      contractile vacuoles along the ventral side of the cell. A. eigneri differs from
      its congeners, inter alia, by the marine habitat, the presence of many
      contractile vacuoles along the ventral margin and the number of somatic kineties
      on both sides. Loxophyllum ozakii Shigematsu, 1953 is transferred to
      Kentrophyllum.

PMID- 17202083
TI  - Introduction: improving oncology nursing through advances in quality-of-life
      issues.

PMID- 17202084
TI  - Advances in how clinical nurses can evaluate and improve quality of life for
      individuals with cancer.
AB  - PURPOSE/OBJECTIVES: To describe advances in the ways that clinical nurses
      understand, assess, and work to improve quality of life (QOL) for individuals
      with cancer since the 1995 Oncology Nursing Society's State-of-the-Knowledge
      Conference on QOL. DATA SOURCES: Published research and clinical articles. DATA
      SYNTHESIS: The number of QOL assessment tools and methods for understanding QOL
      results has increased. However, scant literature has focused on how clinical
      oncology nurses evaluate QOL and the methods they use to affect QOL for
      individuals with cancer. CONCLUSIONS: Based on the nurse-patient relationship,
      clinical nurses are able to assess QOL in individuals with cancer and intervene
      appropriately to improve QOL. IMPLICATIONS FOR NURSING: Clinical nurses can
      involve individuals with cancer in rating their QOL to assist in providing high
      quality care that is directed at positively affecting QOL.

PMID- 17202085
TI  - Measurement issues in quality-of-life assessments.
AB  - PURPOSE/OBJECTIVES: To describe issues to be considered when measuring the
      quality of life (QOL) of patients with cancer. DATA SOURCES: Published articles
      and books, conference proceedings, and abstracts. DATA SYNTHESIS: A review of the
      existing literature reveals an emerging field of research and considerable
      discussion of measurement issues. Consensus is growing about measurement
      approaches to this subjective concept; however, agreement differs regarding
      specific aspects of measurement approaches and interpretation of data.
      CONCLUSIONS: The purpose of the QOL assessment and how the data will be analyzed
      are the main determinants of the choice of assessment and measurement approaches.
      Differences regarding how QOL is measured may be encountered based on a clinical
      or research purpose. IMPLICATIONS FOR NURSING: QOL assessments may be used as
      part of data collection to address a specific research question or may be used to
      guide clinical practice. Research findings used to guide clinical practice should
      be evaluated for validity, reliability, and fit of the sample before being
      incorporated into clinical practice. QOL assessment in clinical practice may be
      used as an exploratory tool to identify potential problems or may be used to
      evaluate the effectiveness of a targeted intervention.

PMID- 17202087
TI  - Infusing culture into oncology research on quality of life.
AB  - PURPOSE/OBJECTIVES: To review the literature relevant to understanding culturally
      informed oncology research, particularly as it relates to health-related quality
      of life. DATA SOURCES: Published articles and books. DATA SYNTHESIS: A cultural
      perspective to the prevailing theory and research methods used in oncology
      research with respect to quality of life is imperative. A multidimensional and
      practical framework can be applied to increase cultural competence in research by
      addressing the purpose of the research, theoretical framework, and methodologic
      approaches. CONCLUSIONS: Culturally competent, multicultural research will help
      the scientific community better comprehend disparities that exist in health
      related quality of life so that benefits can be experienced by all patients.
      IMPLICATIONS FOR NURSING: Nursing practice and research must continue its
      leadership role to infuse cultural competence and reduce disparities in the
      healthcare system.

PMID- 17202086
TI  - Advances in defining, conceptualizing, and measuring quality of life in pediatric
      patients with cancer.
AB  - PURPOSE/OBJECTIVES: To describe the notable advances in defining,
      conceptualizing, and measuring quality of life (QOL) in pediatric patients with
      cancer since the 1995 Oncology Nursing Society's State-of-the-Knowledge
      Conference on QOL. DATA SOURCES: Published research, clinical papers, and
      hospital policies. DATA SYNTHESIS: QOL ratings from children and adolescents are
      being solicited increasingly in research and clinical assessments during
      treatment and survivorship using various methods but are not solicited from
      terminally ill patients; qualitatively induced models of pediatric cancer-related
      QOL now are being tested using quantitative methods. CONCLUSIONS: Children aged
      five years and older are able to report their cancer-related QOL; reliable and
      valid QOL instruments exist for all phases of treatment except end of life.
      IMPLICATIONS FOR NURSING: Nurses can involve children and adolescents in rating
      their QOL for research and clinical purposes and can apply theory-based QOL
      models to direct care.

PMID- 17202088
TI  - Participation of the C-terminal region of the D1-polypeptide in the first steps
      in the assembly of the Mn4Ca cluster of photosystem II.
AB  - Amino acid residue D1-Asp(170) of the D1-polypeptide of photosystem II was
      previously shown to be implicated in the binding and oxidation of the first
      manganese to be assembled into the Mn(4)Ca cluster of the oxygen-evolving complex
      (OEC). According to recent x-ray crystallographic structures of photosystem II,
      D1-Glu(333) is proposed to participate with D1-Asp(170) in the coordination of
      Mn4 of the OEC. Other residues in the C-terminal region of the D1-polypeptide are
      proposed to coordinate nearby manganese of the cluster. Site-directed
      replacements in Synechocystis sp. PCC 6803 at D1-His(332), D1-Glu(333), D1
      Asp(342), D1-Ala(344), and D1-Ser(345) were examined with regard to their ability
      to influence the binding and oxidation of the first manganese in manganese
      depleted photosystem II core complexes. Direct and indirect measurements reveal
      in all mutants, but most marked in D1-Glu(333) replaced by His, an impaired
      ability of Mn(2+) to reduce Y(Z)., indicating a reduced ability (elevated K(m))
      compared with WT to bind and oxidize the first manganese of the OEC. The effect
      on the K(m) of these mutations is, however, considerably weaker than some of
      those constructed at D1-Asp(170) (replacement by Asn, Ala, and Ser). These
      observations imply that the C-terminal residues ultimately involved in manganese
      coordination contribute to the high affinity binding at D1-Asp(170) likely
      through electrostatic interactions. That these residues are far from D1-Asp(170)
      in the primary structure of the D1-polypeptide, imply that the C terminus of the
      D1-polypeptide is already close to its mature conformation at the first stages of
      assembly of the Mn(4)Ca cluster.

PMID- 17202089
TI  - Clinical impact of chronic renal insufficiency on endovascular aneurysm repair.
AB  - Endovascular aneurysm repair of abdominal aortic aneurysms has become a viable
      alternative to open repair. A significant proportion of this patient population
      has chronic renal insufficiency. The surgical outcomes associated with
      endovascular repair in 342 patients, with and without chronic renal
      insufficiency, are reported. Perioperative mortality, length of admission, length
      of intensive care unit admission, and rates of acute renal failure, congestive
      heart failure, myocardial infarction, conversion to open surgery, progression to
      hemodialysis, and incidence of endoleaks were retrospectively reviewed and
      analyzed. Endovascular repair demonstrated higher rates of acute renal failure,
      longer length of stay, and longer intensive care unit admissions in patients with
      chronic renal insufficiency. Patients with severe renal dysfunction demonstrated
      markedly elevated mortality and morbidity. These results indicate that chronic
      renal insufficiency is not an absolute contraindication to endovascular repair in
      patients with moderate renal dysfunction, but patients with severe renal
      dysfunction perform poorly after aortic reconstruction.

PMID- 17202090
TI  - CryoPlasty therapy of the superficial femoral and popliteal arteries: a single
      center experience.
AB  - Long-term patency remains a significant hurdle in the minimally invasive
      treatment of arteriosclerosis in the superficial femoral and popliteal arteries.
      New technologies designed to address the sources of restenosis have recently been
      introduced. CryoPlasty therapy (Boston Scientific, Natick, Mass) is a new
      approach designed to significantly reduce injury, elastic recoil, stent
      implantation, neointimal hyperplasia, and constrictive remodeling. The technique
      combines the dilatation forces of percutaneous transluminal angioplasty with cold
      thermal energy applied to the plaque and vessel wall. The cumulative effect of
      limiting the sources of restenosis with CryoPlasty therapy was shown to
      demonstrate longer term patency in a prospective, multicenter, Investigational
      Device Exemption study of the PolarCath Peripheral Dilatation System. The
      CryoPlasty therapy experience of 1 center is reported, in which 47 lesions in 32
      consecutive patients (34 procedures, 33 limbs) were treated. The technical
      success rate was 96%. There were no type 3 flow-limiting dissections, and only 4
      (8.5%) lesions were stented. There were no unanticipated adverse events,
      specifically no thrombus, acute occlusions, distal embolizations, aneurysms, or
      groin complications. With an average follow-up of 12 months, only 5 lesions have
      recurred, 4 requiring re-intervention. The 12-month freedom from restenosis for
      lesions and limbs treated was 82.2% and 84.4%, respectively. These results are
      similar to the findings of the Investigational Device Exemption study and are
      encouraging. CryoPlasty therapy appears to be a viable endovascular therapeutic
      option to achieve longer term patency without compromising options for future
      interventions. The lack of early occlusions may be due to a low rate of spiral
      dissection that may be a particular benefit of this form of angioplasty.

PMID- 17202091
TI  - Endoluminal management of arterioportal fistulae in liver transplant recipients:
      a single-center experience.
AB  - Transcatheter embolization of arterioportal fistulae in liver transplant
      recipients is restricted to symptomatic arterioportal fistulae. Angiograms of
      liver transplant recipients from a single university medical center were
      retrospectively reviewed. Hemodynamically significant arterioportal fistulae were
      defined as those exhibiting opacification of the main portal vein of the
      transplanted hepatic graft or its first order branch with or without portal
      venous changes by Doppler ultrasound imaging. Six arterioportal fistulae were
      found. Doppler ultrasound imaging detected 50% of all arterioportal fistulae and
      all 3 hemodynamically significant arterioportal fistulae. Three successful
      embolizations were performed. Follow-up (37 to 67 months) demonstrated patent
      hepatic arteries and no parenchymal ischemic changes with graft preservation.
      High-throughput arterioportal fistulae may require larger intrahepatic artery
      branch embolization. There is a window of opportunity for embolizing significant
      arterioportal fistulae before their progression to large symptomatic, high
      through-put arterioportal fistulae with their added risk of ischemic changes
      before and after embolization.

PMID- 17202092
TI  - Endovascular exclusion of popliteal artery aneurysms with expanded
      polytetrafluoroethylene stent-grafts: early results.
AB  - There is increasing interest in using endovascular methods instead of surgical
      reconstruction to treat popliteal artery aneurysms. Exclusive use of the Viabahn
      stent-graft, a nitinol stent covered with expanded polytetrafluoroethylene, was
      assessed in the treatment of patients who presented with popliteal artery
      aneurysms in the absence of acute limb ischemia. Technical success, endoleaks,
      graft patency, freedom from amputation, and aneurysm sac flow and size changes
      were assessed by duplex ultrasound. From June 2004 to March 2006, 16 men (mean
      age, 76 years; range, 65-83) underwent endovascular exclusion of 23 popliteal
      artery aneurysms (mean diameter, 2.5 cm; range, 1.3-6.7 cm). Nine lesions had
      partial thrombus on preprocedural duplex imaging. Nineteen of the 23 limbs
      treated had at least 2-vessel tibial artery runoff. Procedures were performed
      under local anesthesia using ipsilateral percutaneous antegrade arterial access.
      All patients received 75 mg/day of clopidogrel afterward. Follow-up assessments
      included direct clinical examinations and duplex ultrasonography performed 1, 3,
      6, and 12 months after the procedure. Primary patency and amputation-free
      survival were calculated using Kaplan-Meier analysis. Complete aneurysm exclusion
      (technical success) was achieved in all cases. During the mean follow-up of 7
      months (range, 1-21 months), 22 of 23 treated limbs remained asymptomatic. One
      stent-graft thrombosis occurred 6 months after the procedure and was successfully
      treated with percutaneous mechanical thrombectomy, balloon angioplasty of a stent
      graft stenosis, and insertion of an uncovered nitinol stent. No popliteal artery
      aneurysm sac size enlargements or endoleaks were detected. At 12 months, the
      treated limb mean ankle-brachial index was 1.0 (range, 0.82-1.31) and the primary
      and secondary patency rates were 93% and 100%, respectively. Early results with
      Viabahn endovascular stent-graft exclusion of asymptomatic popliteal artery
      aneurysms are promising. Patient selection for endovascular repair depends on
      suitable popliteal artery anatomy, extent of aneurysmal degeneration, and quality
      of tibial arterial runoff.

PMID- 17202094
TI  - Creation of arteriovenous fistulas upregulates venous eNOS.

PMID- 17202093
TI  - A multidisciplinary approach to carotid paragangliomas.
AB  - The surgical management of carotid paragangliomas can be problematic. A
      multidisciplinary approach was used to include vascular surgery, otolaryngology,
      and neuroradiology to treat these patients over 9 years. From January 1992 to
      July 2001, a multidisciplinary team evaluated patients with carotid
      paragangliomas. Analyzed patient data included age, gender, diagnostic
      evaluation, tumor size, preoperative tumor embolization, operative exposure, need
      for extracranial arterial sacrifice/reconstruction, postoperative morbidity
      including cranial nerve dysfunction, and long-term follow-up. Twenty-five carotid
      paragangliomas in 20 patients underwent multidisciplinary evaluation and
      management. Average age was 51 years (range, 28-83 years), and 52% were male.
      Diagnostic evaluation included computed tomography in 76%, magnetic resonance
      imaging/magnetic resonance angiography in 52%, catheter angiography in 60%, and
      duplex ultrasonography in 16%. An extended neck exposure was required in 11 cases
      (44%), mandibulotomy was used once (4%), and mandibular subluxation was never
      required. The external carotid artery (ECA) was sacrificed in 8 cases (32%). The
      carotid bifurcation was resected in 1 patient (4%) requiring interposition
      reconstruction of the internal carotid artery. Preoperative tumor embolization
      was performed for 13 tumors (52%). Operative blood loss for patients undergoing
      preoperative embolization (Group I) was comparable to the nonembolized group
      (group II): group I lost 365 +/-180 mL versus 360 +/- 101 mL for group II (P =
      .48). This occurred despite larger tumors (group I - 4.2 cm versus group II - 2.1
      cm, P = .03) and a higher mean Shamblin class (group I - 2.5 versus group II -
      1.45, P = .001) for group I. There were no perioperative mortalities. Transient
      cranial nerve dysfunction occurred in 13 CBTs (52%), 2 (8%) of which remained
      present after 4 months. Patients with carotid paragangliomas benefit from a
      multidisciplinary team approach. Neuroradiology has been used for selective
      preoperative embolization, which has decreased estimated blood loss during
      excision of larger complex tumors. A combined surgical team of otolaryngology and
      vascular surgery provides for exposure of the distal internal carotid artery as
      high as the skull base, limited permanent cranial nerve dysfunction, and
      selective early division and excision of the external carotid artery for complete
      tumor resection.

PMID- 17202095
TI  - Comparison of intraoperative completion flowmeter versus duplex ultrasonography
      and contrast arteriography for carotid endarterectomy.
AB  - Intraoperative completion studies of the internal carotid artery following
      carotid endarterectomy are recommended to ensure technical perfection of the
      repair. Transit time ultrasound flowmeter does not require trained technicians,
      requires less time than other completion studies such as duplex ultrasonography
      and contrast arteriography, and is noninvasive. Flowmetry was compared with
      duplex ultrasonography and contrast arteriography to determine if the relatively
      simpler flowmetry could replace these two more widely accepted completion studies
      in the intraoperative assessment of carotid endarterectomy. Comparative
      intraoperative assessment was performed in 116 carotid endarterectomies using all
      three techniques between December 1, 2000 and November 30, 2003. Eversion
      endarterectomy was performed in 51 cases and standard endarterectomy with
      prosthetic patching in 65 cases. Patients underwent completion flowmetry, duplex
      ultrasonography, and contrast arteriography studies of the exposed arteries,
      which were performed by vascular fellows or senior surgical residents under
      direct supervision of board-certified vascular surgeons. Duplex ultrasonography
      surveillance was performed 1 and 6 months postoperatively and annually
      thereafter. Mean follow-up was 18 months (range, 6-42 months). The combined
      ipsilateral stroke and death rate was 0%. The mean internal carotid artery flow
      using flowmetry was 249 mL/min (range, 60-750 mL/min). Five (4.3%) patients had
      flow < 100 mL/min as measured with flowmetry, but completion contrast
      arteriography and duplex ultrasonography were normal and none of the arteries
      were re-explored. One carotid endarterectomy was re-explored based on completion
      duplex ultrasonography that showed markedly elevated internal carotid artery peak
      systolic velocity (> 500 cm/sec); however, exploration was normal and completion
      flowmetry and contrast arteriography were normal. Duplex ultrasonography studies
      revealed internal carotid artery peak systolic velocities > 150 cm/sec in 15
      patients, but flowmetry and contrast arteriography were normal in all 15 cases
      and none of the arteries were re-explored. There was no correlation between flow
      rates measured using flowmetry and peak systolic velocities measured using duplex
      ultrasonography. One abnormal contrast arteriogram showed an intimal flap that
      was revised, but duplex ultrasonography and flowmetry were normal. Severe
      recurrent internal carotid artery stenosis developed in 2 patients at 6 and 9
      months, but all 3 completion intraoperative studies at the time of the original
      operation were normal. Based on these results, wide variability in flowmetry
      values limits its potential usefulness to detect non-flow-limiting lesions and
      replace contrast arteriography or duplex ultrasonography as an intraoperative
      carotid endarterectomy completion study. Duplex ultrasonography was also of
      limited to no value, whereas contrast arteriography rarely documented a lesion
      that required repair.

PMID- 17202096
TI  - Aortoenteric fistula: a late complication of endovascular repair of an
      inflammatory abdominal aortic aneurysm.
AB  - Endovascular repair provides a reasonable alternative to open repair for the
      treatment of abdominal aortic aneurysms in select cases. Although the
      endovascular approach may be preferable for inflammatory aneurysms, aggressive
      surveillance is needed to monitor for long-term complications. A 61-year-old man
      underwent endovascular exclusion of a symptomatic inflammatory abdominal aortic
      aneurysm with an AneuRx bifurcated aortic prosthesis. He presented with
      gastrointestinal bleeding 51/2 months later and was found to have an aortoenteric
      fistula involving the third portion of the duodenum. The aneurysm had expanded
      significantly at the proximal neck. The patient underwent successful removal of
      the device, aortic ligation, and extraanatomic bypass. Aortoenteric fistula is a
      rare but now established complication of endovascular aneurysm repair. The
      pathophysiology in these cases remains unclear. The presence of inflammation and
      endoleak may predispose to further aneurysmal degeneration.

PMID- 17202098
TI  - Multiple penetrating atherosclerotic ulcers of the aorta: report of a case.
AB  - A 69-year-old hypertensive man who had 7 pseudoaneurysms caused by penetrating
      atherosclerotic ulcers underwent 2-staged endovascular grafting in the thoracic
      and thoracoabdominal aorta and a conventional graft replacement of the abdominal
      aorta. He had an uneventful postoperative course; follow-up computed tomography
      demonstrated that all aneurysmal lesions treated by endovascular grafting
      completely disappeared. He has been free from any aortic events 20 months after
      the last surgery.

PMID- 17202099
TI  - Traumatic pseudoaneurysm of the popliteal artery after blunt trauma: case report
      and a review of the literature.
AB  - Pseudoaneurysms of the popliteal artery following trauma are rare lesions. We
      present 3 cases of pseudoaneurysms of the popliteal artery (4, 20, and 45 years
      old respectively) with a delayed presentation, following blunt trauma, presenting
      over a 3-year period, and a short review of the relevant literature. A delayed
      pattern of presentation, over 2 years after blunt popliteal trauma, was observed
      in all patients. They presented with a painful pulsatile mass in the popliteal
      fossa, and their peripheral pulses were normal. Orthopedic and rheumatologic
      evaluation findings were negative. Diagnostic evaluation included triplex,
      arteriography, and computed tomography angiography. A posterior popliteal
      approach was used, and after aneurysmal excision, reversed great saphenous vein
      and lesser saphenous vein (1 patient) grafts were used. After 2 to 4 years of
      follow-up, all grafts remain patent and the patients have fully functional limbs.
      A literature search revealed 70 cases of pseudoaneurysms of the popliteal artery
      reported in civilian settings. These lesions should be repaired shortly because
      their complications (rupture, thromboembolic episodes) carry a high risk for limb
      dysfunction and amputation. Penetrating or blunt trauma is the main causative
      factor (62.5%), but iatrogenic trauma accounts for an increasing number of
      reports (37.5%). Strict follow-up of popliteal trauma is essential. A high level
      of suspicion and awareness can lead to early diagnosis and treatment of
      pseudoaneurysms of the popliteal artery and prevent the serious complications
      associated with these lesions.

PMID- 17202097
TI  - Iatrogenic limb ischemia caused by angiography closure devices.
AB  - Described are 2 cases of lower limb ischemia that resulted after deployment of 2
      different arterial closure devices. One patient presented acutely with lower limb
      ischemia after an Angio-Seal (St Jude Medical, Minnetonka, Minn) device deployed
      at the conclusion of cerebral artery aneurysm embolization. The second patient,
      who underwent angioplasty for aortic recoarctation, presented with claudication 1
      week after deployment of the Perclose (Perclose, Redwood City, Calif) device. The
      use of such devices can result in significant complications, and cardiologists,
      interventional radiologists, and vascular surgeons are advised to have a high
      index of suspicion for such complications and work in close conjunction to
      provide prompt and adequate treatment.

PMID- 17202100
TI  - Surgical treatment of ovarian vein thrombosis.
AB  - Ovarian vein thrombosis is a rare but serious condition that may cause sepsis in
      the postpartum patient or may be associated with thrombosis of the inferior vena
      cava or renal vein. A 30-year-old woman presented 2 weeks postpartum with sudden
      onset of dyspnea and rightsided pleuritic chest pain. She was diagnosed with a
      large pulmonary embolus and thrombosis of the right ovarian vein. After failure
      of percutaneous embolization of the right ovarian vein, the patient underwent
      open surgical excision of the right ovarian vein. The management of ovarian vein
      thrombosis may involve systemic anticoagulation, antibiotics, thrombolysis, open
      surgical treatment, or a combination of these.

PMID- 17202101
TI  - Primary intimal sarcoma of the aorta associated with a dacron graft and resulting
      in arterial rupture.
AB  - Primary arterial neoplasms are rare lesions which have been most frequently
      associated with local or constitutional symptomatology, and with distal
      embolization. Perirenal aortic disruption with pseudoaneurysm formation due to an
      intimal sarcoma adjacent to a previously placed prosthetic graft is reported in a
      66-year-old man. This case supports the premise that the presence of a vascular
      prosthesis might result in the induction of an arterial wall malignancy. This
      should be considered when an intraluminal mass is identified in the absence of
      other arterial pathology. Although the prognosis of these tumors is poor, their
      preoperative recognition may enhance treatment outcomes.

PMID- 17202102
TI  - The forest and the trees: the human costs of cancer.

PMID- 17202103
TI  - Retinoblastoma survivors: sarcomas and surveillance.

PMID- 17202104
TI  - Conflict-of-interest rules worry some scientists.

PMID- 17202106
TI  - Democratic Congress could mean more money and more oversight for NIH.

PMID- 17202107
TI  - Efforts to communicate clinical trial results to patients face uphill climb.

PMID- 17202108
TI  - Stat bite: Smokers and education level.

PMID- 17202109
TI  - Patient time costs associated with cancer care.
AB  - BACKGROUND: Although costs of medical care for cancer have been investigated
      extensively, patient time costs associated with cancer care have rarely been
      estimated systematically. In this study, we estimated patient time costs
      associated with cancer care in patients aged 65 years and older in the United
      States. METHODS: We identified 763,527 patients with breast, colorectal, corpus
      uteri, gastric, head and neck, lung, melanoma of the skin, ovary, prostate,
      renal, and urinary bladder cancers from linked Surveillance, Epidemiology, and
      End Results-Medicare files and 1,145,159 noncancer control subjects among
      Medicare enrollees who were matched by sex, age-group, and geographic location.
      Frequency of service use was calculated by category for patients and control
      subjects using Medicare claims data from 1995 to 2001. For each service category,
      time estimates were combined with service frequency and an hourly value of
      patient time. Net patient time costs were summed in the initial, continuing, and
      last-year-of-life phases of care for each tumor site. Net time cost estimates for
      the initial phase of care were applied to national estimates of numbers of new
      cancers in 2005 to obtain national time costs for the initial phase of care.
      RESULTS: Net patient time costs during the initial phase of care ranged from 271
      dollars (95% confidence interval [CI] = 213 dollars to 329 dollars) and 842
      dollars (95% CI = 806 dollars to 878 dollars) for melanoma of the skin and
      prostate cancer, respectively, to 5348 dollars (95% CI = 4978 dollars to 5718
      dollars) and 5605 dollars (95% CI = 5273 dollars to 5937 dollars) for gastric and
      ovarian cancers, respectively. Net patient time costs for care during the last
      year of life ranged from 1509 dollars (95% CI = 1343 dollars to 1675 dollars) for
      melanoma of the skin to 7799 dollars (95% CI = 7433 dollars to 8165 dollars),
      7435 dollars (95% CI = 7207 dollars to 7663 dollars), and 7388 dollars (95% CI =
      7018 dollars to 7758 dollars) for gastric, lung, and ovarian cancers,
      respectively. In 2005, patient time costs for the initial phase of care were 2.3
      billion dollars. CONCLUSIONS: Patient time costs for cancer care in the United
      States are substantial and vary by tumor site and phase of care, likely
      reflecting differences in stage at diagnosis and availability and intensity of
      treatment.

PMID- 17202111
TI  - Statin use and risk of colorectal cancer.
AB  - BACKGROUND: Statins have anticancer activity in various cell types, including
      colon cancer cells. Although epidemiologic data on the relationship between
      statin use and the risk of colorectal cancer are limited, one case-control study
      reported a 50% reduction in colorectal cancer risk among statin users. We
      conducted a population-based case-control study to assess this association with
      respect to statin type, dose, and duration of use. METHODS: Case patients with
      adenocarcinoma of the colon or rectum were ascertained from participating
      hospitals in Massachusetts and the Massachusetts Cancer Registry from January 1,
      2001, through November 30, 2004. Age-, sex-, and precinct-matched control
      subjects were chosen from Massachusetts town lists. Information on statin use and
      other relevant data were obtained by telephone interview. We used multivariable
      conditional logistic regression models to estimate odds ratios (ORs). All tests
      for statistical significance were two-sided. RESULTS: Among 1809 case patients
      and 1809 matched control subjects, regular use of statins for at least 3 months
      was not associated with the risk of colorectal cancer (OR = 0.92, 95% confidence
      interval [CI] = 0.78 to 1.09). There was no consistent trend across dose or
      duration of use (e.g., for > or = 10 years of use, OR = 0.86, 95% CI = 0.51 to
      1.45). The risk of stage IV cancer was, however, statistically significantly
      lower among statin users than among nonusers (OR = 0.49, 95% CI = 0.26 to 0.91).
      There was no evidence of an interaction between statin use and nonsteroidal anti
      inflammatory drug use. CONCLUSIONS: Overall, use of statins did not appear to be
      associated with reduced risk of colorectal cancer. The reduced risk of stage IV
      cancer observed among statin users requires confirmation.

PMID- 17202110
TI  - Risk of soft tissue sarcomas by individual subtype in survivors of hereditary
      retinoblastoma.
AB  - BACKGROUND: Survivors of hereditary retinoblastoma have an increased risk for
      second malignancies, especially soft tissue sarcomas. However, the risks of
      individual histologic subtypes of soft tissue sarcomas have not been evaluated.
      METHODS: We estimated the risk for six subtypes of soft tissue sarcomas
      (fibrosarcoma, liposarcoma, histiocytoma, leiomyosarcoma, rhabdomyosarcoma, and
      others) in a cohort of 963 one-year survivors of hereditary retinoblastoma among
      patients diagnosed at two US institutions from 1914 through 1984. We calculated
      standardized incidence ratios (SIRs) for specific subtypes of soft tissue
      sarcomas by comparison with population data from the Connecticut Tumor Registry
      or from National Cancer Institute Surveillance, Epidemiology, and End Results
      database. We also calculated the cumulative risk for all soft tissue sarcomas
      combined. RESULTS: We observed 69 soft tissue sarcomas in 68 patients with
      hereditary retinoblastoma. Risks were elevated for soft tissue sarcomas overall
      (SIR = 184, 95% confidence interval [CI] = 143 to 233) and for individual
      subtypes. Leiomyosarcoma was the most frequent subtype (SIR = 390, 95% CI = 247
      to 585), with 78% of leiomyosarcomas diagnosed 30 or more years after the
      retinoblastoma diagnosis (SIR = 435, 95% CI = 258 to 687). Among patients treated
      with radiotherapy for retinoblastoma, we found statistically significantly
      increased risks of soft tissue sarcomas in the field of radiation. Irradiated
      patients also had increased risks of soft tissue sarcomas, especially
      leiomyosarcomas, outside the field of radiation, and risks of soft tissue
      sarcomas were increased in nonirradiated patients as well, indicating a genetic
      predisposition to soft tissue sarcomas independent of radiation. The cumulative
      risk for any soft tissue sarcoma 50 years after radiotherapy for retinoblastoma
      was 13.1% (95% CI = 9.7% to 17.0%). CONCLUSION: Long-term follow-up of a cohort
      of survivors of hereditary retinoblastoma revealed a statistically significant
      excess of leiomyosarcoma and other soft tissue sarcomas that persists decades
      after the retinoblastoma diagnosis. Retinoblastoma survivors should undergo
      regular medical surveillance for sarcomas in their adult years.

PMID- 17202112
TI  - Lysosomes and trivalent arsenic treatment in acute promyelocytic leukemia.
AB  - BACKGROUND: Cells from patients with t(15;17) acute promyelocytic leukemia (APL)
      express the fusion protein between the promyelocytic leukemia protein and
      retinoic acid receptor alpha (PML/RAR alpha). Patients with APL respond to
      differentiation therapy with all-trans-retinoic acid, which induces PML/RAR alpha
      degradation. When resistance to all-trans-retinoic acid develops, an effective
      treatment is arsenic trioxide (arsenite), which also induces this degradation. We
      investigated the mechanism of arsenite-induced PML/RAR alpha degradation.
      METHODS: NB4-S1 APL cells were treated with clinically relevant concentrations of
      arsenite. Lysosomes were visualized with a lysosome-specific dye. Lysosomal
      protein esterase was measured by immunoblot analysis. Lysosomal cathepsin L was
      detected by immunogold labeling and transmission electron microscopy, and its
      activity was measured in cytosolic cellular fractions. In vitro degradation
      assays of PML/RAR alpha in cell lysates were performed with and without protease
      inhibitors and assessed by immunoblot analysis. Only nonparametric two-sided
      statistical analyses were used. The nonparametric Wilcoxon test was used for
      group comparison, and the nonlinear regression technique was used for analysis of
      dose-response relationship as a function of arsenite concentration. RESULTS:
      Arsenite treatment destabilized lysosomes in APL cells. Lysosomal proteases,
      including cathepsin L, were released from lysosomes 5 minutes to 6 hours after
      arsenite treatment. PML/RAR alpha was degraded by lysate from arsenite-treated
      APL cells, and the degradation was inhibited by protease inhibitors. At both 6
      and 24 hours, substantially fewer arsenite-treated APL cells, than untreated
      cells, contained cathepsin L clusters, a reflection of cathepsin L
      delocalization. Cells with cathepsin L clusters decreased as a function of
      arsenite concentration at rates of -2.03% (95% confidence interval [CI] = -4.01
      to -.045; P = .045) and -2.39% (95% CI = -4.54 to -.024; P = .029) in 6- and 24
      hour treatment groups, respectively, per 1.0 microM increase in arsenite
      concentration. Statistically significantly higher cytosolic cathepsin L activity
      was detected in lysates of arsenite-treated APL cells than in control lysates.
      For example, the mean increase in cathepsin activity at 6 hours and 1.0 microM
      arsenite was 26.3% (95% CI = 3.3% to 33%; P < .001), compared with untreated
      cells. CONCLUSIONS: In APL cells, arsenite may cause rapid destabilization of
      lysosomes.

PMID- 17202113
TI  - Magnetic resonance imaging of temperature-sensitive liposome release: drug dose
      painting and antitumor effects.
AB  - BACKGROUND: In preclinical studies, lysolipid-based temperature-sensitive
      liposomes (LTSLs) containing chemotherapy drugs administered in combination with
      local hyperthermia have been found to increase tumor drug concentrations and
      improve antitumor efficacy of the drugs. We used a novel magnetic resonance
      imaging (MRI) method to measure the temporal and spatial patterns of drug
      delivery in a rat fibrosarcoma model during treatment with LTSLs containing
      doxorubicin and an MRI contrast agent (manganese) (Dox/Mn-LTSLs) administered at
      different times with respect to hyperthermia. METHODS: Rats bearing 10- to 12-mm
      fibrosarcomas (n = 6-7 per group) were treated with Dox/Mn-LTSLs (at a dose of 5
      mg doxorubicin/kg body weight) before and/or during 60 minutes of local tumor
      hyperthermia administered via a catheter inserted at the center of the tumor.
      Drug distribution was monitored continuously via MRI. Magnetic resonance changes
      were used to calculate intratumoral doxorubicin concentrations throughout
      treatment. Tumors were monitored until they reached five times their volume on
      the day of treatment or 60 days. Doxorubicin concentrations and times for tumors
      to reach five times their volume on the day of treatment were analyzed using the
      Kruskal-Wallis test and the Kaplan-Meier product-limit method, respectively. All
      statistical tests were two-sided. RESULTS: Administration of Dox/Mn-LTSLs before,
      during, and both before and during hyperthermia yielded central, peripheral, and
      uniform drug distributions, respectively. Doxorubicin accumulated more quickly
      and reached higher concentrations in the tumor when Dox/Mn-LTSLs were
      administered during hyperthermia than when administered before hyperthermia
      (rate: 9.8 versus 1.8 microg/min, difference = 8.0 microg/min, 95% confidence
      interval [CI] = 6.8 to 12.8 microg/min, P = .003; concentration: 15.1 versus 8.0
      ng/mg, difference = 7.1 ng/mg, 95% CI = 3.6 to 10.6 ng/mg, P = .028). LTSL
      administered during hyperthermia also yielded the greatest antitumor effect, with
      a median time for tumors to reach five times their volume on the day of treatment
      of 34 days (95% CI = 30 days to infinity) compared with 18.5 days (95% CI = 16 to
      23 days) for LTSL before hyperthermia and 22.5 days (95% CI = 15 to 25 days) for
      LTSL before and during hyperthermia. CONCLUSIONS: In this rat fibrosarcoma model,
      LTSLs were most effective when delivered during hyperthermia, which resulted in a
      peripheral drug distribution.

PMID- 17202114
TI  - Folate and risk of breast cancer: a meta-analysis.
AB  - BACKGROUND: Epidemiologic findings are inconsistent concerning risk for breast
      cancer associated with low folate intake or blood folate levels. We performed a
      meta-analysis of prospective and case-control studies to examine folate intake
      and levels in relation to risk of breast cancer. METHODS: We searched MEDLINE for
      studies of this association that were published in any language from January 1,
      1966, through November 1, 2006. Study-specific risk estimates were pooled by use
      of a random-effects model. All statistical tests were two-sided. RESULTS: Folate
      intake in increments of 200 microg/day was not associated with the risk of breast
      cancer in prospective studies (estimated summary relative risk [RR] = 0.97, 95%
      confidence interval [CI] = 0.88 to 1.07, for dietary folate [eight studies;
      302,959 participants and 8367 patients with breast cancer], and RR = 1.01, 95% CI
      = 0.97 to 1.05, for total folate [six studies; 306,209 participants and 8165
      patients with breast cancer]) but was statistically significantly inversely
      associated with risk in case-control studies (estimated summary odds ratio [OR] =
      0.80, 95% CI = 0.72 to 0.89, for dietary folate [13 studies; 8558 case patients
      and 10,812 control subjects], and OR = 0.93, 95% CI = 0.81 to 1.07, for total
      folate [three studies; 2184 case patients and 3233 control subjects]). High blood
      folate levels versus low levels were not statistically significantly associated
      with the risk of breast cancer in prospective studies (OR = 0.81, 95% CI = 0.59
      to 1.10 [three studies]) or in case-control studies (OR = 0.41, 95% CI = 0.15 to
      1.10 [two studies]). Among the two prospective studies and two case-control
      studies that stratified by alcohol consumption, high folate intake (comparing the
      highest with the lowest category) was associated with a statistically significant
      decreased risk of breast cancer among women with moderate or high alcohol
      consumption (summary estimate = 0.51, 95% CI = 0.41 to 0.63) but not among women
      with low or no alcohol consumption (summary estimate = 0.95, 95% CI = 0.78 to
      1.15). Few studies examined whether the relation between folate intake and breast
      cancer was modified by intakes of methionine or vitamins B6 and B12, and the
      findings were inconsistent. CONCLUSION: No clear support for an overall
      relationship between folate intake or blood folate levels and breast cancer risk
      was found. Adequate folate intake may reduce the increased risk of breast cancer
      that has been associated with moderate or high alcohol consumption.

PMID- 17202115
TI  - Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal
      Study cohort.
AB  - Recent studies have suggested the involvement of loci on the Y chromosome in
      prostate cancer. We studied the relative risk (RR) of prostate cancer in relation
      to sex ratio of offspring in a cohort of 38,934 Israeli men who were followed
      from the birth of their offspring (in 1964 through 1976) until 2005. Cox models
      were used to adjust for changes in incidence over time, age, the man's year of
      birth, and social and ethnic variables. A total of 712 men were diagnosed with
      prostate cancer. Compared with men who had at least one son, men with only
      daughters had an increased risk of prostate cancer (adjusted RR = 1.40, 95%
      confidence interval [CI] = 1.20 to 1.64, P<.0001). In men with one, two, or three
      or more offspring, the relative risks associated with absence of sons were 1.25
      (95% CI = 1.00 to 1.56), 1.41 (95% CI = 1.04 to 1.91), and 1.60 (95% CI = 1.05 to
      2.43), respectively. Men with no daughters showed no statistically significantly
      altered risk, compared with men who had offspring of both sexes. The relative
      risk of prostate cancer decreased as the number of sons increased
      (P(trend)<.0001) but did not change with the number of daughters. These findings
      suggest that a Y chromosome locus may be involved in prostate cancer risk in this
      population.

PMID- 17202116
TI  - Hypothyroidism in patients with metastatic renal cell carcinoma treated with
      sunitinib.
AB  - Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet
      derived growth factor receptors, and it has antitumor activity in metastatic
      renal cell carcinoma and gastrointestinal stromal tumors. To further investigate
      the fatigue associated with sunitinib therapy, thyroid function tests were
      performed on patients with metastatic renal cell carcinoma who were receiving
      sunitinib. Seventy-three patients with metastatic renal cell carcinoma were
      treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of
      them had thyroid function test results available. Fifty-six (85%) of the 66
      patients had one or more abnormality in their thyroid function test results,
      consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal
      thyroid function tests had signs and/or symptoms possibly related to
      hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and
      symptoms improved in nine of them. Thyroid function test abnormalities appear to
      be common in patients with metastatic renal cell carcinoma treated with
      sunitinib, and routine monitoring is warranted.

PMID- 17202118
TI  - Re: Variations in hospice use among cancer patients.

PMID- 17202119
TI  - Bevacizumab-induced cardiovascular events: a consequence of cholesterol emboli
      syndrome?

PMID- 17202120
TI  - Has demand for clinical trial participants outpaced supply?

PMID- 17202122
TI  - Mass spectrometry technologies for proteomics.
AB  - In the late 1980s, the advent of soft ionization techniques capable of generating
      stable gas phase ions from thermally unstable biomolecules, namely matrix
      assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI),
      laid the way for the development of a set of powerful alternatives to the
      traditional Edman chemistry for the structural characterization of peptides and
      proteins. The rapid protein identification capabilities that, coupled with two
      dimensional gel electrophoresis, provided insights into all sorts of biological
      systems since the dawn of proteomics and have been exploited in the last few
      years for the development of more powerful and automatable gel-free strategies,
      mainly based on multidimensional chromatographic separations of peptides from
      proteolytic digests. In parallel to the evolution of ion sources, mass analysers
      and scan modes, the invention of new elegant biochemical strategies to
      fractionate or simplify highly complex mixtures, or to introduce isotopic labels
      in peptides in a variety of ways now makes also possible large-scale, high
      coverage quantitative studies in a wide dynamic range. In this review, we provide
      the fundamental concepts of mass spectrometry (MS) and describe the technological
      progress of MS-based proteomics since its earliest days. Representative
      literature examples of their true power, either when employed as exploratory or
      as targeted techniques, is provided as well.

PMID- 17202123
TI  - Identifying neuropeptide and protein hormone receptors in Drosophila melanogaster
      by exploiting genomic data.
AB  - Most neuropeptide and protein hormone receptors belong to the large superfamily
      of G-protein-coupled receptors (GPCRs). These cell membrane proteins steer many
      important processes such as development, reproduction, homeostasis and behaviour
      when activated by their corresponding ligands. The first insect genome, that of
      the fruitfly Drosophila melanogaster, was sequenced in 2000, and about 200 GPCRs
      have been annnotated in this model insect. About 50 of these receptors were
      predicted to have neuropeptides or protein hormones as their ligands. Since 2000,
      the cDNAs of most of these candidate receptors have been cloned and for many
      receptors the endogenous ligand has been identified. In this review, we will give
      an update about the current knowledge of all Drosophila neuropeptide and protein
      hormone receptors, and discuss their phylogenetic relationships.

PMID- 17202124
TI  - Designing experiments that aid in the identification of regulatory networks.
AB  - Predictive mathematical models of the interactions of a genetic network can
      provide insight into the mechanisms of gene regulation, the role of various genes
      within a network and how multiple genes interact leading to complex traits.
      However, identification of the parameters and interactions is currently a
      limiting step in the development of such models. This work reviews the state of
      the art for design of experiments in biological systems and demonstrates the need
      for improved design of experiments through the use of a model system. Appropriate
      design of experiments has a profound impact on the ability to identify a model
      and on the quality of resulting identified model. Key issues include the
      selection of appropriate input sequences (e.g. random, independent multivariate
      inputs) and the selection of the sampling frequencies. This work demonstrates
      that these issues are especially important in the identification of biochemical
      networks and that the traditional biochemical approach is incapable of truly
      identifying the behavior present in such networks.

PMID- 17202125
TI  - Functional genomics of abiotic stress tolerance in cereals.
AB  - Abiotic stresses such as extreme temperatures, low water availability, high salt
      and mineral deficiencies or toxicities severely diminish productivity of cereal
      crops. These stresses are becoming increasingly important because of the
      declining availability of good quality water, land degradation and community
      pressures to move away from chemical intervention in agriculture. Of the major
      cereals, wheat and barley are grown in the most hostile and consequently lowest
      yielding environments. Extensive genetic studies and surveys of landrace and wild
      germplasm have indicated extensive variation for abiotic stress tolerance but
      this has been difficult to exploit due to the relatively poor background
      knowledge of the molecular basis for stress in these species. Interconnected
      signal transduction pathways that lead to multiple responses to abiotic stresses
      have been difficult to study using traditional approaches because of their
      complexity and the large number of genes and gene products involved in the
      various defensive and developmental responses of the plant. Functional genomics
      is now widely seen as providing tools for dissecting abiotic stress responses in
      wheat and barley, through which networks of stress perception, signal
      transduction and defensive responses can be examined from gene transcription,
      through protein complements of cells, to the metabolite profiles of stressed
      tissues.

PMID- 17202127
TI  - Characterizing phosphoproteins and phosphoproteomes using mass spectrometry.
AB  - The reversible phosphorylation of proteins plays a major role in many vital
      cellular processes by modulating protein function and transmitting signals within
      cellular pathways and networks. Because phosphorylation is dynamic and the sites
      of modification cannot be predicted by an organism's genome, proteomic
      measurements are required to identify sites of and changes in the phosphorylation
      state of proteins. The low stoichiometry of phosphorylation sites that accompany
      the multifarious nature of protein phosphorylation in biological systems
      continues to challenge the dynamic range of present mass spectrometry (MS)
      technologies and proteomic measurements, despite the preponderance of research
      and analytical methods devoted to this area. This review addresses some of the
      strategies and limitations involving the use of MS to map and quantify changes in
      protein phosphorylation sites for samples that range from a single protein to an
      entire proteome, and presents several compelling reasons as to why comprehensive
      phosphorylation site analysis has proven to be so elusive without a hypothesis
      driven experimental approach to elicit more meaningful and confident results.

PMID- 17202126
TI  - Transcriptomics, proteomics and interactomics: unique approaches to track the
      insights of bioremediation.
AB  - Microbial mediated bioremediation has a great potential to effectively restore
      contaminated environment, but the lack of information about factors regulating
      the growth and metabolism of various microbial communities in polluted
      environment often limits its implementation. Newly seeded techniques such as
      transcriptomics, proteomics and interactomics offer remarkable promise as tools
      to address longstanding questions regarding the molecular mechanisms involved in
      the control of mineralization pathways. During mineralization, transcript
      structures and their expression have been studied using high-throughput
      transcriptomic techniques with microarrays. Generally however, transcripts have
      no ability to operate any physiological response; rather, they must be translated
      into proteins with significant functional impact. These proteins can be
      identified by proteomic techniques using powerful two-dimensional polyacrylamide
      gel electrophoresis (2-DE). Towards the establishment of functional proteomics,
      the current advances in mass spectrometry (MS) and protein microarrays play a
      central role in the proteomics approach. Exploring the differential expression of
      a wide variety of proteins and screening of the entire genome for proteins that
      interact with particular mineralization regulatory factors would help us to gain
      insights into bioremediation.

PMID- 17202128
TI  - Altered brain lipid composition in cyclooxygenase-2 knockout mouse.
AB  - Cyclooxygenase (COX)-2 plays an important role in brain arachidonic acid (20:4n
      6) metabolism, and its expression is upregulated in animal models of
      neuroinflammation and excitotoxicity. Our hypothesis was that brain lipid
      composition would be altered in COX-2 knockout (COX-2(-/-)) compared with wild
      type (COX-2(+/+)) mice, reflecting the important role of COX-2 in brain lipid
      metabolism. Concentrations of different lipids were measured in high-energy
      microwaved brain from COX-2(-/-) and COX-2(+/+) mice. Compared with the COX
      2(+/+) mouse brain, the brain of the COX-2(-/-) mouse had a statistically
      significant 15% increase in phosphatidylserine (PtdSer) and significant 37, 27,
      and 32% reductions in triacylglycerol and cholesterol concentrations and in the
      cholesterol-to-phospholipid ratio, respectively. The normalized concentration of
      palmitic acid (16:0) was increased in PtdSer, as was the brain concentration of
      unesterified arachidic acid (20:0). A lifetime absence of COX-2 produces multiple
      changes in brain lipid composition. These changes may be related to reported
      changes in fatty acid kinetics and in resistance to neuroinflammation and
      excitotoxicity in the COX-2(-/-) mouse.

PMID- 17202129
TI  - Effects of forced uncoupling protein 1 expression in 3T3-L1 cells on
      mitochondrial function and lipid metabolism.
AB  - Obesity-related increase in body fat mass is a risk factor for many diseases,
      including type 2 diabetes. Controlling adiposity by targeted modulation of
      adipocyte enzymes could offer an attractive alternative to current dietary
      approaches. Brown adipose tissue, which is present in rodents but not in adult
      humans, expresses the mitochondrial uncoupling protein 1 (UCP1) that promotes
      cellular energy dissipation as heat. Here, we report on the direct metabolic
      effects of forced UCP1 expression in white adipocytes derived from a murine (3T3
      L1) preadipocyte cell line. After stable integration, the ucp1 gene product was
      continuously expressed during differentiation and reduced the total lipid
      accumulation by approximately 30% without affecting other adipocyte markers, such
      as cytosolic glycerol-3-phosphate dehydrogenase activity and leptin production.
      The expression of UCP1 also decreased glycerol output and increased glucose
      uptake, lactate output, and the sensitivity of cellular ATP content to nutrient
      removal. However, oxygen consumption and beta-oxidation were minimally affected.
      Together, our results suggest that the reduction in intracellular lipid by
      constitutive expression of UCP1 reflects a downregulation of fat synthesis rather
      than an upregulation of fatty acid oxidation.

PMID- 17202130
TI  - The role of TNF-alpha in chronic inflammatory conditions, intermediary
      metabolism, and cardiovascular risk.
AB  - The recent insight that inflammation contributes to the development of
      atherosclerosis and type 2 diabetes mellitus constitutes a major breakthrough in
      understanding the mechanisms underlying these conditions. In addition, it opens
      the way for new therapeutic approaches that might eventually decrease the
      prevalence of these public health problems. Tumor necrosis factor-alpha (TNF
      alpha) has been shown to play a key role in these processes and thus might be a
      potential therapeutic target. Increased concentrations of TNF-alpha are found in
      acute and chronic inflammatory conditions (e.g., trauma, sepsis, infection,
      rheumatoid arthritis), in which a shift toward a proatherogenic lipid profile and
      impaired glucose tolerance occurs. Although therapeutic blockade of TNF-alpha
      worsens the prognosis in patients with abscesses and granulomatous infections,
      this strategy is highly beneficial in the case of chronic inflammatory
      conditions, including rheumatoid arthritis. Current investigations assessing the
      impact of anti-TNF agents on intermediary metabolism suggest that TNF-alpha
      blockade may improve insulin resistance and lipid profiles in patients with
      chronic inflammatory diseases.

PMID- 17202131
TI  - Conserved intermolecular salt bridge required for activation of protein kinases
      PKR, GCN2, and PERK.
AB  - The protein kinases PKR, GCN2, and PERK phosphorylate translation initiation
      factor eIF2alpha to regulate general and genespecific protein synthesis under
      various cellular stress conditions. Recent x-ray crystallographic structures of
      PKR and GCN2 revealed distinct dimeric configurations of the kinase domains.
      Whereas PKR kinase domains dimerized in a back-to-back and parallel orientation,
      the GCN2 kinase domains displayed an antiparallel orientation. The dimerization
      interfaces on PKR and GCN2 were localized to overlapping surfaces on the N
      terminal lobes of the kinase domains but utilized different intermolecular
      contacts. A key feature of the PKR dimerization interface is a salt bridge
      interaction between Arg(262) from one protomer and Asp(266) from the second
      protomer. Interestingly, these two residues are conserved in all eIF2alpha
      kinases, although in the GCN2 structure, the two residues are too remote to
      interact. To test the importance of this potential salt bridge interaction in
      PKR, GCN2, and PERK, the residues constituting the salt bridge were mutated
      either independently or together to residues with the opposite charge. Single
      mutations of the Asp (or Glu) and Arg residues blocked kinase function both in
      yeast cells and in vitro. However, for all three kinases, the double mutation
      designed to restore the salt bridge interaction with opposite polarity resulted
      in a functional kinase. Thus, the salt bridge interaction and dimer interface
      observed in the PKR structure is critical for the activity of all three eIF2alpha
      kinases. These results are consistent with the notion that the PKR structure
      represents the active state of the eIF2alpha kinase domain, whereas the GCN2
      structure may represent an inactive state of the kinase.

PMID- 17202132
TI  - Phosphorylation of protein phosphatase 1 by cyclin-dependent protein kinase 5
      during nerve growth factor-induced PC12 cell differentiation.
AB  - The transcription factor Egr-1 activates cyclin-dependent protein kinase 5 (Cdk5)
      during nerve growth factor (NGF)-induced differentiation of PC12 cells into
      neurons (Harada, T. Morooka, T., Ogawa, S., and Nishida, E. (2001) Nat. Cell
      Biol. 3, 453-459). The downstream target of Cdk5 in the Egr-1/Cdk5 pathway is not
      clear. In this study, we observed that phosphorylation of protein phosphatase 1
      (PP1) on Thr(320) is reduced in brain extracts from Egr-1(-/-) mice, indicating
      that a kinase downstream of Egr-1 phosphorylates PP1. In HEK 293 cells co
      transfected with PP1 and Cdk5, Cdk5 phosphorylates PP1. In vitro, Cdk5 purified
      from bovine brain phosphorylates bacterially expressed recombinant PP1. In NGF
      treated PC12 cells, inhibition of Cdk5 by olomoucine or silencing Cdk5 expression
      by small interfering RNA strategy, suppresses PP1 phosphorylation. Silencing Cdk5
      expression by small interfering RNA also blocks NGF-induced neurite outgrowth.
      Overexpression of PP1 (wild type) promotes NGF-induced differentiation of PC12
      cells, whereas that of PP1 (T320A) has no effect. Our data indicate that PP1 is a
      downstream target of the NGF/Egr-1/Cdk5 pathway during NGF-induced
      differentiation of PC12 cells and suggest that PP1 phosphorylation promotes
      neuronal differentiation.

PMID- 17202134
TI  - IDI2, a second isopentenyl diphosphate isomerase in mammals.
AB  - We recently described the identification of a novel isopentenyl diphosphate
      isomerase, IDI2 in humans and mice. Our current data indicate that, in humans,
      IDI2 is expressed only in skeletal muscle. Expression constructs of human IDI2 in
      Saccharomyces cerevisiae can complement isomerase function in an idi1-deficient
      yeast strain. Furthermore, IDI2 has the ability to catalyze the isomerization of
      [(14)C]IPP to [(14)C]DMAPP. Enzyme kinetic analysis of partially purified IDI2
      demonstrate the novel isozyme has a maximal relative specific activity of 1.2 x
      10(-1) +/- 0.3 micromol min(-1) mg(-1) at pH 8.0 with a K(IPP)(m) value of 22.8
      microm IPP. Both isozymes, IDI1 and IDI2 are localized to the peroxisome by a
      PTS1-dependent pathway. Finally, our data suggest that IDI2 is regulated
      independently from IDI1, by a mechanism that may involve PPARalpha.

PMID- 17202133
TI  - Functional and intracellular signaling differences associated with the
      Helicobacter pylori AlpAB adhesin from Western and East Asian strains.
AB  - Following adhesion of Helicobacter pylori to gastric epithelial cells,
      intracellular signaling leads to cytokine production, which causes H. pylori
      related gastric injury. Two adjacent homologous genes (alpA and alpB), which
      encode H. pylori outer membrane proteins, are thought to be associated with
      adhesion and cytokine induction. We co-cultured gastric epithelial cells with
      wild type H. pylori strains and their corresponding alpA/alpB-deleted mutants
      (DeltaalpAB). Results were confirmed by complementation. Flow cytometry confirmed
      that AlpAB was involved in cellular adhesion. Deletion of alpAB reduced
      interleukin (IL)-6 induction in gastric epithelial cells. Deletion of alpAB
      reduced IL-8 induction with East Asian but not with Western strains. All AlpAB
      positive strains tested activated the extracellular signal-regulated kinase, c
      Fos, and cAMP-responsive element-binding protein. Activation of the Jun-N
      terminal kinase, c-Jun, and NF-kappaB was exclusive to AlpAB from East Asian
      strains. DeltaalpAB mutants poorly colonized the stomachs of C57BL/6 mice and
      were associated with lower mucosal levels of KC and IL-6. Our results suggest
      that AlpAB may induce gastric injury by mediating adherence to gastric epithelial
      cells and by modulating proinflammatory intracellular signaling cascades. Known
      geographical differences in H. pylori-related clinical outcomes may relate to
      differential effects of East Asian and Western types of AlpAB on NF-kappaB
      related proinflammatory signaling pathways.

PMID- 17202135
TI  - The glucose transporter 4-regulating protein TUG is essential for highly insulin
      responsive glucose uptake in 3T3-L1 adipocytes.
AB  - Insulin stimulates glucose uptake in fat and muscle by redistributing GLUT4
      glucose transporters from intracellular membranes to the cell surface. We
      previously proposed that, in 3T3-L1 adipocytes, TUG retains GLUT4 within
      unstimulated cells and insulin mobilizes this retained GLUT4 by stimulating its
      dissociation from TUG. Yet the relative importance of this action in the overall
      control of glucose uptake remains uncertain. Here we report that transient, small
      interfering RNA-mediated depletion of TUG causes GLUT4 translocation and enhances
      glucose uptake in unstimulated 3T3-L1 adipocytes, similar to insulin. Stable TUG
      depletion or expression of a dominant negative fragment likewise stimulates GLUT4
      redistribution and glucose uptake, and insulin causes a 2-fold further increase.
      Microscopy shows that TUG governs the accumulation of GLUT4 in perinuclear
      membranes distinct from endosomes and indicates that it is this pool of GLUT4
      that is mobilized by TUG disruption. Interestingly, in addition to translocating
      GLUT4 and enhancing glucose uptake, TUG disruption appears to accelerate the
      degradation of GLUT4 in lysosomes. Finally, we find that TUG binds directly and
      specifically to a large intracellular loop in GLUT4. Together, these findings
      demonstrate that TUG is required to retain GLUT4 intracellularly in 3T3-L1
      adipocytes in the absence of insulin and further implicate the insulin-stimulated
      dissociation of TUG and GLUT4 as an important action by which insulin stimulates
      glucose uptake.

PMID- 17202136
TI  - A histidine-rich cluster mediates the ubiquitination and degradation of the human
      zinc transporter, hZIP4, and protects against zinc cytotoxicity.
AB  - Zinc is an essential nutrient. Genetic evidence for this nutritional requirement
      in humans is the zinc deficiency disease, acrodermatitis enteropathica. This
      disorder is caused by mutations in hZIP4 (SLC39A4), a zinc importer required for
      zinc uptake in enterocytes and other cell types. Studies in mice have
      demonstrated that levels of the mZIP4 mRNA are reduced by elevated dietary zinc,
      resulting in a decreased abundance of the ZIP4 protein at the plasma membrane.
      Moreover, studies in cultured cells have demonstrated that low micromolar
      concentrations of zinc stimulate the endocytosis of the mZIP4 protein resulting
      in a reduction in cellular zinc uptake. In this study, we demonstrate an
      additional level of hZIP4 regulation involving ubiquitination and degradation of
      this transporter in elevated zinc concentrations. Mutational analysis identified
      a cytoplasmic histidine-rich domain that was essential for ubiquitin-dependent
      degradation of ZIP4 and protection against zinc toxicity. However, this motif was
      dispensable for zinc-induced endocytosis. These findings indicate that ubiquitin
      mediated degradation of the ZIP4 protein is critical for regulating zinc
      homeostasis in response to the upper tier of physiological zinc concentrations,
      via a process that is distinct from zinc-stimulated endocytosis.

PMID- 17202137
TI  - Activation of multifarious transcription of an adhesion protein ap65-1 gene by a
      novel Myb2 protein in the protozoan parasite Trichomonas vaginalis.
AB  - Multifarious transcription of the adhesion protein ap65-1 gene in the human
      pathogen, Trichomonas vaginalis, is critically regulated by the coordination of
      two similar but opposite oriented DNA regulatory regions, MRE-1/MRE-2r and MRE
      2f, both of which are binding sites for multiple Myb-like proteins. In the
      present study, MRE-1/MRE-2r was demonstrated to be composed of multiple
      overlapping promoter elements, among which the entire region is required for
      growth-related ap65-1 transcription, and the 5'-MRE-1 antagonizes the suppressive
      activity of the 3'-MRE-2r in iron-inducible transcription. The recombinant Myb2
      protein derived from a previously identified myb2 gene was demonstrated to
      recognize distinct sequence contexts in MRE-2r and MRE-2f, whereas Myb2 in the
      nuclear lysate preferentially binds to MRE-2f to MRE-2r. Iron repletion resulted
      in persistent repression of the myb2 gene, and temporal activation/deactivation
      of Myb2 promoter entry, which was also activated by prolonged iron depletion. The
      hemagglutinintagged Myb2 when overexpressed during iron-depleted conditions
      facilitated basal and growth-related ap65-1 transcription to a level that was
      achieved in iron-replete cells, whereas ironinducible ap65-1 transcription was
      abolished with knockdown of Myb2. These findings demonstrated that Myb2 is
      involved in activation of growth-related and iron-inducible transcription of the
      ap65-1 gene, possibly through differential promoter selection in competition with
      other Myb proteins.

PMID- 17202138
TI  - Transforming growth factor-beta-independent regulation of myogenesis by SnoN
      sumoylation.
AB  - Recent progress has been made on the role of oncoproteins c-Ski and related SnoN
      in the control of cellular transformation. c-Ski/SnoN potently repress
      transforming growth factor-beta (TGF-beta) antiproliferative signaling through
      physical interaction with signal transducers called Smads. Overexpression of c
      Ski/SnoN also induces skeletal muscle differentiation, but how c-Ski/SnoN
      function in myogenesis is largely unknown. During our investigation on the role
      of sumoylation in TGF-beta signaling, we inadvertently found that SnoN is
      modified by small ubiquitin-like modifier-1 (SUMO-1). Here, we biochemically
      characterize SnoN sumoylation in detail and report the physiological function of
      the modification. Sumoylation occurs primarily at lysine 50 (Lys-50). PIAS1 and
      PIASx proteins physically interact with SnoN to stimulate its sumoylation, thus
      serving as SUMO-protein isopeptide ligases (E3) for SnoN sumoylation. SnoN
      sumoylation does not alter its metabolic stability or its ability to repress TGF
      beta signaling. Notably, loss of sumoylation in the Lys-50 site (via a Lys-to-Arg
      point mutation) potently activates muscle-specific gene expression and enhances
      myotube formation. Our study suggests a novel role for SUMO modification in the
      regulation of myogenic differentiation.

PMID- 17202139
TI  - Tautomerism of histidine 64 associated with proton transfer in catalysis of
      carbonic anhydrase.
AB  - The imidazole (15)N signals of histidine 64 (His(64)), involved in the catalytic
      function of human carbonic anhydrase II (hCAII), were assigned unambiguously.
      This was accomplished by incorporating the labeled histidine as probes for
      solution NMR analysis, with (15)N at ring-N(delta1) and N(epsilon2), (13)Cat ring
      Cepsilon1, (13)C and (15)N at all carbon and nitrogen, or (15)N at the amide
      nitrogen and the labeled glycine with (13)C at the carbonyl carbon. Using the pH
      dependence of ring-(15)N signals and a comparison between experimental and
      simulated curves, we determined that the tautomeric equilibrium constant (K(T))
      of His(64) is 1.0, which differs from that of other histidine residues. This
      unique value characterizes the imidazole nitrogen atoms of His(64) as both a
      general acid (a) and base (b): its epsilon2-nitrogen as (a) releases one proton
      into the bulk, whereas its delta1-nitrogen as (b) extracts another proton from a
      water molecule within the water bridge coupling to the zinc-bound water inside
      the cave. This accelerates the generation of zinc-bound hydroxide to react with
      the carbon dioxide. Releasing the productive bicarbonate ion from the inside
      separates the water bridge pathway, in which the next water molecules move into
      beside zinc ion. A new water molecule is supplied from the bulk to near the
      delta1-nitrogen of His(64). These reconstitute the water bridge. Based on these
      features, we suggest here a catalytic mechanism for hCAII: the tautomerization of
      His(64) can mediate the transfers of both protons and water molecules at a
      neutral pH with high efficiency, requiring no time- or energy-consuming
      processes.

PMID- 17202140
TI  - Affinity and kinetic analysis of Fcgamma receptor IIIa (CD16a) binding to IgG
      ligands.
AB  - Binding of pathogen-bound immunoglobulin G (IgG) to cell surface Fc gamma
      receptors (FcgammaRs) triggers a wide variety of effector functions. The binding
      kinetics and affinities of IgG-FcgammaR interactions are hence important
      parameters for understanding FcgammaR-mediated immune functions. We have measured
      the kinetic rates and equilibrium dissociation constants of IgG binding to a
      soluble FcgammaRIIIa fused with Ig Fc (sCD16a) using the surface plasmon
      resonance technique. sCD16a interacted with monomeric human IgG and its subtypes
      IgG1 and IgG3 as well as rabbit IgG with on-rates of 6.5 x 10(3), 8.2 x 10(3),
      1.1 x 10(4) and 1.8 x 10(4) m(-1) s(-1), off-rates of 4.7 x 10(-3), 5.7 x 10(-3),
      5.9 x 10(-3), and 1.9 x 10(-2) s(-1), and equilibrium dissociation constants of
      0.72, 0.71, 0.56, and 1.1 mum, respectively. The kinetics and affinities measured
      by surface plasmon resonance agreed with those obtained from real time flow
      cytometry and competition inhibition binding experiments using cell surface
      CD16a. These data add to our understanding of IgG-FcgammaR interactions.

PMID- 17202141
TI  - Protein kinase A-dependent translocation of Hsp90 alpha impairs endothelial
      nitric-oxide synthase activity in high glucose and diabetes.
AB  - Diabetes mellitus (DM) and high glucose (HG) are known to reduce the
      bioavailability of nitric oxide (NO) by modulating endothelial nitric-oxide
      synthase (eNOS) activity. eNOS is regulated by several mechanisms including its
      interaction with heat shock protein (Hsp) 90. We previously discovered that DM in
      vivo and HG in vitro induced the translocation of Hsp90alpha to the outside of
      aortic endothelial cells. In this report we tested the hypothesis that
      translocation of Hsp90alpha is responsible for the decline in NO production
      observed in HG-treated cells. We found that HG increased phosphorylation of
      Hsp90alpha in a cAMP-dependent protein kinase A-dependent manner, and that this
      event was required for translocation of Hsp90alpha in porcine aortic endothelial
      cells. Furthermore, preventing translocation of Hsp90alpha protected from the HG
      induced decline in eNOS.Hsp90alpha complex and NO production. Notably, DM
      increased phosphorylation of Hsp90alpha and reduced its association with eNOS in
      the aortic endothelium of diabetic rats. These studies suggest that translocation
      of Hsp90alpha is a novel mechanism by which HG and DM impair eNOS activity and
      thereby reduce NO production.

PMID- 17202142
TI  - alpha-ketoglutaric semialdehyde dehydrogenase isozymes involved in metabolic
      pathways of D-glucarate, D-galactarate, and hydroxy-L-proline. Molecular and
      metabolic convergent evolution.
AB  - Azospirillum brasilense possesses an alternative pathway of l-arabinose
      metabolism in which alpha-ketoglutaric semialdehyde (alphaKGSA) dehydrogenase
      (KGSADH) is involved in the last step, the conversion of alphaKGSA to alpha
      ketoglutarate. In the preceding studies, we identified a set of metabolic genes
      of the l-arabinose pathway including the KGSADH gene (Watanabe, S., Kodaki, T.,
      and Makino, K. (2006) J. Biol. Chem. 281, 2612-2623; Watanabe, S., Kodaki, T.,
      and Makino, K. (2006) J. Biol. Chem. 281, 28876-28888; Watanabe, S., Shimada, N.,
      Tajima, K., Kodaki, T., and Makino, K. (2006) J. Biol. Chem. 281, 33521-33536).
      Here, we describe that A. brasilense possesses two different KGSADH isozymes from
      l-arabinose-related enzyme (KGSADH-I); that is, d-glucarate/d-galactarate
      inducible KGSADH-II and hydroxy-l-proline-inducible KGSADH-III. They were
      purified homogeneously from A. brasilense cells grown on d-galactarate or hydroxy
      l-proline, respectively. When compared with KGSADH-I, amino acid sequences of
      KGSADH-II and KGSADH-III were significantly similar but not totally identical.
      Physiological characterization using recombinant enzymes revealed that KGSADH-II
      and KGSADH-III showed similar high substrate specificity for alphaKGSA and
      different coenzyme specificity; that is, NAD(+)-dependent KGSADH-II and NADP(+)
      dependent KGSADH-III. In the phylogenetic tree of the aldehyde dehydrogenase
      (ALDH) superfamily, KGSADH-II and KGSADH-III were poorly related to the known
      ALDH subclasses including KGSADH-I. On the other hand, ALDH-like ycbD protein
      involved in d-glucarate/d-galactarate operon from Bacillus subtilis is closely
      related to the methylmalonyl semialdehyde dehydrogenase subclass but not A.
      brasilense KGSADH isozymes. To estimate the correct function, the corresponding
      gene was expressed, purified, and characterized. Kinetic analysis revealed the
      physiological role as NADP(+)-dependent KGSADH. We conclude that three different
      types of KGSADH appeared in the bacterial evolutional stage convergently.
      Furthermore, even the same pathway such as l-arabinose and d-glucarate/d
      galactarate metabolism also evolved by the independent involvement of KGSADH.

PMID- 17202143
TI  - Heparin binding induces a conformational change in pigment epithelium-derived
      factor.
AB  - Pigment epithelium-derived factor (PEDF) is a noninhibitory serpin found in
      plasma and in the extracellular space. The protein is involved in different
      biological processes including cell differentiation and survival. In addition, it
      is a potent inhibitor of angiogenesis. The function is likely associated with
      binding to cell surface receptors in a heparin-dependent way (Alberdi, E. M.,
      Weldon, J. E., and Becerra, S. P. (2003) BMC Biochem. 4, 1). We have investigated
      the structural basis for this observation and show that heparin induces a
      conformational change in the vicinity of Lys(178). This structural change was
      evident both when binding to intact heparin and specific heparin-derived
      oligosaccharides at physiological conditions or simply when exposing PEDF to low
      ionic strength. Binding to other glycosaminoglycans, heparin-derived
      oligosaccharides smaller than hexadecasaccharides (dp16), or type I collagen did
      not affect the structure of PEDF. The conformational change is likely to expose
      the epitope involved in binding to the receptor and thus regulates the
      interactions with cell surface receptors.

PMID- 17202144
TI  - Insulin-like growth factor 1/insulin signaling activates androgen signaling
      through direct interactions of Foxo1 with androgen receptor.
AB  - The androgen-androgen receptor (AR) system plays vital roles in a wide array of
      biological processes, including prostate cancer development and progression.
      Several growth factors, such as insulin-like growth factor 1 (IGF1), can induce
      AR activation, whereas insulin resistance and hyperinsulinemia are correlated
      with an elevated incidence of prostate cancer. Here we report that Foxo1, a
      downstream molecule that becomes phosphorylated and inactivated by
      phosphatidylinositol 3-kinase/Akt kinase in response to IGF1 or insulin,
      suppresses ligand-mediated AR transactivation. Foxo1 reduces androgen-induced AR
      target gene expressions and suppresses the in vitro growth of prostate cancer
      cells. These inhibitory effects of Foxo1 are attenuated by IGF1 but are enhanced
      when it is rendered Akt-nonphosphorylatable. Foxo1 interacts directly with the C
      terminus of AR in a ligand-dependent manner and disrupts ligand-induced AR
      subnuclear compartmentalization. Foxo1 is recruited by liganded AR to the
      chromatin of AR target gene promoters, where it interferes with AR-DNA
      interactions. IGF1 or insulin abolish the Foxo1 occupancy of these promoters. Of
      interest, a positive feedback circuit working locally in an autocrine/intracrine
      manner may exist, because liganded AR up-regulates IGF1 receptor expression in
      prostate cancer cells, presumably resulting in higher IGF1 signaling tension and
      further enhancing the functions of the receptor itself. Thus, Foxo1 is a novel
      corepressor for AR, and IGF1/insulin signaling may confer stimulatory effects on
      AR by attenuating Foxo1 inhibition. These results highlight the potential
      involvement of metabolic syndrome and hyperinsulinemia in prostate diseases and
      further suggest that intervention of IGF1/insulin-phosphatidylinositol 3-kinase
      Akt signaling may be of clinical value for prostate diseases.

PMID- 17202145
TI  - The Cytoplasmic domain of transferrin receptor 2 dictates its stability and
      response to holo-transferrin in Hep3B cells.
AB  - Transferrin receptor 2 (TfR2) is a homolog of transferrin receptor 1 (TfR1), the
      receptor responsible for the uptake of iron-loaded transferrin (holo-Tf) into
      cells. Unlike the ubiquitous TfR1, TfR2 is predominantly expressed in the liver.
      Mutations in TfR2 gene cause a rare autosomal recessive form of the iron overload
      disease, hereditary hemochromatosis. Previous studies demonstrated that holo-Tf
      increases TfR2 levels by stabilizing TfR2 at the protein level. In this study we
      constructed two chimeras, one of which had the cytoplasmic domain of TfR2 and the
      remaining portion of TfR1 and the other with the cytoplasmic and transmembrane
      domain of TfR1 joined to the ectodomain of TfR2. Similar to TfR2, the levels of
      the chimera containing only the cytoplasmic domain of TfR2 increased in a time-
      and dose-dependent manner after the addition of holo-Tf to the medium. The half
      life of the chimera increased 2.7-fold in cells exposed to holo-Tf like the
      endogenous TfR2 in HepG2 cells. Like TfR2 and unlike TfR1, the levels of the
      chimera did not respond to intracellular iron content. These results suggest that
      although holo-Tf binding to the ectodomain is necessary, the cytoplasmic domain
      of TfR2 is largely responsible for its stabilization by holo-Tf.

PMID- 17202146
TI  - Cannabinoids induce glioma stem-like cell differentiation and inhibit
      gliomagenesis.
AB  - Glioma stem-like cells constitute one of the potential origins of gliomas, and
      therefore, their elimination is an essential factor for the development of
      efficient therapeutic strategies. Cannabinoids are known to exert an antitumoral
      action on gliomas that relies on at least two mechanisms: induction of apoptosis
      of transformed cells and inhibition of tumor angiogenesis. However, whether
      cannabinoids target human glioma stem cells and their potential impact in
      gliomagenesis are unknown. Here, we show that glioma stem-like cells derived from
      glioblastoma multiforme biopsies and the glioma cell lines U87MG and U373MG
      express cannabinoid type 1 (CB(1)) and type 2 (CB(2)) receptors and other
      elements of the endocannabinoid system. In gene array experiments, CB receptor
      activation altered the expression of genes involved in the regulation of stem
      cell proliferation and differentiation. The cannabinoid agonists HU-210 and JWH
      133 promoted glial differentiation in a CB receptor-dependent manner as shown by
      the increased number of S-100beta- and glial fibrillary acidic protein-expressing
      cells. In parallel, cannabinoids decreased the cell population expressing the
      neuroepithelial progenitor marker nestin. Moreover, cannabinoid challenge
      decreased the efficiency of glioma stem-like cells to initiate glioma formation
      in vivo, a finding that correlated with decreased neurosphere formation and cell
      proliferation in secondary xenografts. Gliomas derived from cannabinoid-treated
      cancer stem-like cells were characterized with a panel of neural markers and
      evidenced a more differentiated phenotype and a concomitant decrease in nestin
      expression. Overall, our results demonstrate that cannabinoids target glioma stem
      like cells, promote their differentiation, and inhibit gliomagenesis, thus giving
      further support to their potential use in the management of malignant gliomas.

PMID- 17202147
TI  - Heat shock protein 27 functions in inflammatory gene expression and transforming
      growth factor-beta-activated kinase-1 (TAK1)-mediated signaling.
AB  - Heat shock protein (HSP) 27 has long been known to be a component of the p38
      mitogen-activated protein kinase (MAPK) signaling pathway. p38 MAPK has important
      functions in the inflammatory response, but the role of HSP27 in inflammation has
      remained unknown. We have used small interfering RNAs to suppress HSP27
      expression in HeLa cells and fibroblasts and found that it is required for pro
      inflammatory cell signaling and the expression of pro-inflammatory genes. HSP27
      is needed for the activation by interleukin (IL)-1 of TAK1 and downstream
      signaling by p38 MAPK, JNK, and their activators (MKK-3, -4, -6, -7) and IKKbeta.
      IL-1-induced ERK activation appears to be independent of HSP27. HSP27 is required
      for both IL-1 and TNF-induced signaling pathways for which the most upstream
      common signaling protein is TAK1. HSP27 is also required for IL-1-induced
      expression of the pro-inflammatory mediators, cyclooxygenase-2, IL-6, and IL-8.
      HSP27 functions to drive cyclooxygenase-2 and IL-6 expression by augmenting the
      activation of the kinase downstream of p38 MAPK, MK2, resulting in stabilization
      of cyclooxygenase-2 and IL-6 mRNAs. The mechanism may not occur in cells of
      myeloid lineage because HSP27 protein was undetectable in human monocytes and
      murine macrophages.

PMID- 17202148
TI  - Identification of the extracellular matrix (ECM) binding motifs of tissue
      inhibitor of metalloproteinases (TIMP)-3 and effective transfer to TIMP-1.
AB  - Tissue inhibitor of metalloproteinases (TIMPs) are the endogenous inhibitors of
      the zinc-dependent endopeptidases of the matrix metalloproteinase families. There
      are four mammalian TIMPs (TIMP-1 to -4) but only TIMP-3 is sequestered to the
      extracellular matrix (ECM). The molecular basis for the TIMP-3:ECM association
      has never been fully investigated until now. In this report, we identify the
      unique amino acid configuration that constitutes the basis of the ECM binding
      motif in TIMP-3. By systematically exchanging the subdomains of the TIMPs and
      exhaustive mutation of TIMP-3, we have identified the surface residues directly
      responsible for ECM association. Contrary to the accepted view, we have found
      that TIMP-3 interacts with the ECM via both its N- and C-terminal domains. The
      amino acids involved in ECM binding are all basic in nature: Lys-26, Lys-27, Lys
      30, Lys-76 of the N-terminal domain and Arg-163, Lys-165 of the C-terminal
      domain. Replacement of these residues with glutamate (E) and glutamine (Q)
      (K26/27/30/76E + R163/K165Q) resulted in a soluble TIMP-3 devoid of ECM-adhering
      ability. Using the ECM binding motif derived from TIMP-3, we have also created a
      TIMP-1 mutant (K26/27/30 + K76 transplant) capable of ECM association. This is
      the first instance of TIMPs being intentionally rendered soluble or ECM-bound.
      The ability to prepare TIMPs in soluble or ECM-bound forms also opens new avenues
      for future TIMP research.

PMID- 17202149
TI  - Calcium-dependent and -independent binding of soybean calmodulin isoforms to the
      calmodulin binding domain of tobacco MAPK phosphatase-1.
AB  - The recent finding of an interaction between calmodulin (CaM) and the tobacco
      mitogen-activated protein kinase phosphatase-1 (NtMKP1) establishes an important
      connection between Ca(2+) signaling and the MAPK cascade, two of the most
      important signaling pathways in plant cells. Here we have used different
      biophysical techniques, including fluorescence and NMR spectroscopy as well as
      microcalorimetry, to characterize the binding of soybean CaM isoforms, SCaM-1 and
      -4, to synthetic peptides derived from the CaM binding domain of NtMKP1. We find
      that the actual CaM binding region is shorter than what had previously been
      suggested. Moreover, the peptide binds to the SCaM C-terminal domain even in the
      absence of free Ca(2+) with the single Trp residue of the NtMKP1 peptides buried
      in a solvent-inaccessible hydrophobic region. In the presence of Ca(2+), the
      peptides bind first to the C-terminal lobe of the SCaMs with a nanomolar
      affinity, and at higher peptide concentrations, a second peptide binds to the N
      terminal domain with lower affinity. Thermodynamic analysis demonstrates that the
      formation of the peptide-bound complex with the Ca(2+)-loaded SCaMs is driven by
      favorable binding enthalpy due to a combination of hydrophobic and electrostatic
      interactions. Experiments with CaM proteolytic fragments showed that the two
      domains bind the peptide in an independent manner. To our knowledge, this is the
      first report providing direct evidence for sequential binding of two identical
      peptides of a target protein to CaM. Discussion of the potential biological role
      of this interaction motif is also provided.

PMID- 17202150
TI  - Ceramidase enhances phospholipase C-induced hemolysis by Pseudomonas aeruginosa.
AB  - We previously reported the purification, molecular cloning, and characterization
      of a neutral ceramidase from Pseudomonas aeruginosa strain AN17 (Okino, N., Tani,
      M., Imayama, S., and Ito, M. (1998) J. Biol. Chem. 273, 14368-14373; Okino, N.,
      Ichinose, S., Omori, A., Imayama, S., Nakamura, T., and Ito, M. (1999) J. Biol.
      Chem. 274, 36616-36622). Interestingly, the gene encoding the enzyme is adjacent
      to that encoding hemolytic phospholipase C (plcH) in the genome of Pseudomonas
      aeruginosa, which is a well known pathogen for opportunistic infections. We
      report here that simultaneous production of PlcH and ceramidase was induced by
      several lipids and PlcH-induced hemolysis was significantly enhanced by the
      action of the ceramidase. When the strain was cultured with sphingomyelin or
      phosphatidylcholine, production of both enzymes drastically increased, causing
      the increase of hemolytic activity in the cell-free culture supernatant. Ceramide
      and sphingosine were also effective in promoting the production of ceramidase but
      not that of PlcH. Furthermore, we found that the hemolytic activity of a Bacillus
      cereus sphingomyelinase was significantly enhanced by addition of a recombinant
      Pseudomonas ceramidase. TLC analysis of the erythrocytes showed that ceramide
      produced from sphingomyelin by the sphingomyelinase was partly converted to
      sphingosine by the ceramidase. A ceramidase-null mutant strain caused much less
      hemolysis of sheep erythrocytes than did the wild-type strain. Sphingosine was
      detected in the erythrocytes co-cultured with the wild-type strain but not the
      mutant strain. Finally, we found that the enhancement of PlcH-induced hemolysis
      by the ceramidase occurred in not only sheep but also human erythrocytes. These
      results may indicate that the ceramidase enhances the PlcH-induced cytotoxicity
      and provide new insights into the role of sphingolipid-degrading enzymes in the
      pathogenicity of P. aeruginosa.

PMID- 17202153
TI  - Evidence behind the WHO guidelines: hospital care for children. What are the
      clinical indicators of PCP?

PMID- 17202152
TI  - Virus-induced transcriptional activation of host FUT genes associated with neo
      expression of Ley in cytomegalovirus-infected and sialyl-Lex in varicella-zoster
      virus-infected diploid human cells.
AB  - Cell surface carbohydrate structures including sialyl-Lewis X (sLe(x)) and Lewis
      Y (Le(y)) are important ligands in normal and malignant tissues. The aim here was
      to determine the possible influence on the expression of such antigens by two
      viruses varicella-zoster virus (VZV) and cytomegalovirus (CMV) involved in
      persistent infections of humans. We found that infection of human diploid
      fibroblasts with both viruses resulted in transcriptional activation of several
      fucosyltransferase (FUT) genes that were either dormant or expressed at low
      levels in uninfected cells. Both viruses induced FUT3, FUT5, and FUT6, encoding
      alpha1,3- and/or alpha1,4-specific fucosyltransferases. CMV, but not VZV, induced
      transcription of FUT1 (encoding an alpha1,2-specific fucosyltransferase), FUT7,
      and FUT9. The changes in transcription of FUT genes were expectedly associated
      with expression of Le(y) in CMV-infected cells and sLe(x) in the VZV-infected
      fibroblasts although no expression of these antigens was observed in uninfected
      cells. One major explanation for this difference between CMV- and VZV-infected
      cells was that CMV, but not VZV, induced expression of FUT1, necessary for Le(y)
      expression. The induced carbohydrate antigens in CMV- and VZV-infected cells
      could be of significance for virus spread and possible escape from immune
      responses.

PMID- 17202151
TI  - The dTDP-4-dehydro-6-deoxyglucose reductase encoding fcd gene is part of the
      surface layer glycoprotein glycosylation gene cluster of Geobacillus tepidamans
      GS5-97T.
AB  - The glycan chain of the S-layer protein of Geobacillus tepidamans GS5-97(T)
      consists of disaccharide repeating units composed of L-rhamnose and D-fucose, the
      latter being a rare constituent of prokaryotic glycoconjugates. Although
      biosynthesis of nucleotide-activated L-rhamnose is well established, D-fucose
      biosynthesis is less investigated. The conversion of alpha-D-glucose-1-phosphate
      into thymidine diphosphate (dTDP)-4-dehydro-6-deoxyglucose by the sequential
      action of RmlA (glucose-1-phosphate thymidylyltransferase) and RmlB (dTDP-glucose
      4,6-dehydratase) is shared between the dTDP-D-fucose and the dTDP-L-rhamnose
      biosynthesis pathway. This key intermediate is processed by the dTDP-4-dehydro-6
      deoxyglucose reductase Fcd to form dTDP-alpha-D-fucose. We identified the fcd
      gene in G. tepidamans GS5-97(T) by chromosome walking and performed functional
      characterization of the recombinant 308-amino acid enzyme. The in vitro activity
      of the enzymatic cascade (RmlB and Fcd) was monitored by high-performance liquid
      chromatography and the reaction product was confirmed by (1)H and (13)C nuclear
      magnetic resonance spectroscopy. This is the first characterization of the dTDP
      alpha-D-fucopyranose biosynthesis pathway in a Gram-positive organism. fcd was
      identified as 1 of 20 open reading frames contained in a 17471-bp S-layer
      glycosylation (slg) gene cluster on the chromosome of G. tepidamans GS5-97(T).
      The sgtA structural gene is located immediately upstream of the slg gene cluster
      with an intergenic region of 247 nucleotides. By comparison of the SgtA amino
      acid sequence with the known glycosylation pattern of the S-layer protein SgsE of
      Geobacillus stearothermophilus NRS 2004/3a, two out of the proposed three
      glycosylation sites on SgtA could be identified by electrospray ionization
      quadrupole-time-of-flight mass spectrometry to be at positions Ser-792 and Thr
      583.

PMID- 17202154
TI  - Physical activity and health: evidence from a study of deprived communities in
      England.
AB  - This study aims to explore the relationship between physical activity levels and
      the self-reported health status of residents living in deprived communities in
      England. A cross-sectional interview survey was conducted in communities in
      receipt of funding from the New Deal for Communities (NDC) regeneration
      programme. A sample of 848 addresses was selected by random sampling from within
      each of the 39 NDC areas, and one adult from each household was selected for
      interview. A total of 19 574 residents were interviewed between July and October
      2002. The main outcome measures were physical activity level and health status
      assessed using four self-reported health measures: health in the last 12 months,
      health change in the last 12 months, long-standing illness or disability and a
      mental health-related quality-of-life score. There are large regional and
      demographic variations in respect of NDC residents' physical activity levels. The
      areas with the lowest levels of physical activity are mainly located in northern
      industrial towns. Residents who did little or no physical activity were more than
      twice as likely to feel that their health was not good (adjusted OR 2.54, 95% CI
      2.35-2.75).

PMID- 17202156
TI  - Cooperative binding of the yeast Spt10p activator to the histone upstream
      activating sequences is mediated through an N-terminal dimerization domain.
AB  - The yeast Spt10p activator is a putative histone acetyltransferase (HAT)
      possessing a sequence-specific DNA-binding domain (DBD) which binds to the
      upstream activation sequences (UAS elements) in the histone gene promoters.
      Spt10p binds to a pair of histone UAS elements with extreme positive
      cooperativity. The molecular basis of this cooperativity was addressed. Spt10p
      (640 residues) is an elongated dimer, but the isolated DBD (residues 283-396) is
      a monomer and binds non-cooperatively to DNA. A Spt10p fragment comprising the N
      terminal domain (NTD), HAT domain and DBD (residues 1-396) binds cooperatively
      and is a dimer, whereas an overlapping Spt10p fragment comprising the DBD and C
      terminal domains (residues 283-640) binds non-cooperatively and is a monomer.
      These observations imply that cooperative binding requires dimerization. The
      isolated NTD (residues 1-98) is a dimer and is responsible for dimerization. We
      propose that cooperativity involves a conformational change in the Spt10p dimer
      which facilitates the simultaneous recognition of two UAS elements. In vivo,
      deletion of the NTD results in poor growth, but does not prevent the binding at
      the HTA1 promoter, suggesting that dimerization is biologically important.
      Residues 1-396 are sufficient for normal growth, indicating that the critical
      functions of Spt10p reside in the N-terminal domains.

PMID- 17202157
TI  - DNA methylation immediately adjacent to active histone marking does not silence
      transcription.
AB  - Active promoters generally contain histone H3/H4 hyperacetylation and tri
      methylation at H3 lysine 4, whereas repressed promoters are associated with DNA
      methylation. Here we show that the repressed erythroid-specific carbonic
      anhydrase II (CAII) promoter has active histone modifications localized around
      the transcription start, while high levels of CpG methylation are present
      directly upstream from these active marks. Despite the presence of active histone
      modifications, the repressed promoter requires hormone-induced activation for
      efficient preinitiation complex assembly. Transient and positional changes in
      histone H3/H4 acetylation and local changes in nucleosome density are evident
      during activation, but the bipartite epigenetic code is stably maintained. Our
      results suggest that active histone modifications may prevent spreading of CpG
      methylation towards the promoter and show that repressive DNA methylation
      immediately adjacent to a promoter does not necessarily repress transcription.

PMID- 17202155
TI  - Control of the yeast telomeric senescence survival pathways of recombination by
      the Mec1 and Mec3 DNA damage sensors and RPA.
AB  - Saccharomyces cerevisiae telomerase-negative cells undergo homologous
      recombination on subtelomeric or TG(1-3) telomeric sequences, thus allowing Type
      I or Type II post-senescence survival, respectively. Here, we find that the DNA
      damage sensors, Mec1, Mec3 and Rad24 control Type II recombination, while the
      Rad9 adaptor protein and the Rad53 and Chk1 effector kinases have no effect on
      survivor type selection. Therefore, the Mec1 and Mec3 checkpoint complexes
      control telomeric recombination independently of their roles in generating and
      amplifying the Mec1-Rad53-Chk1 kinase cascade. rfa1-t11 mutant cells, bearing a
      mutation in Replication Protein A (RPA) conferring a defect in recruiting Mec1
      Ddc2, were also deficient in both types of telomeric recombination. Importantly,
      expression of an Rfa1-t11-Ddc2 hybrid fusion protein restored checkpoint
      dependent arrest, but did not rescue defective telomeric recombination.
      Therefore, the Rfa1-t11-associated defect in telomeric recombination is not
      solely due to its failure to recruit Mec1. We have also isolated novel alleles of
      RFA1 that were deficient in Type I but not in Type II recombination and
      proficient in checkpoint control. Therefore, the checkpoint and recombination
      functions of RPA can be genetically separated, as can the RPA-mediated control of
      the two types of telomeric recombination.

PMID- 17202159
TI  - TRED: a transcriptional regulatory element database, new entries and other
      development.
AB  - Transcriptional factors (TFs) and many of their target genes are involved in gene
      regulation at the level of transcription. To decipher gene regulatory networks
      (GRNs) we require a comprehensive and accurate knowledge of transcriptional
      regulatory elements. TRED (http://rulai.cshl.edu/TRED) was designed as a resource
      for gene regulation and function studies. It collects mammalian cis- and trans
      regulatory elements together with experimental evidence. All the regulatory
      elements were mapped on to the assembled genomes. In this new release, we
      included a total of 36 TF families involved in cancer. Accordingly, the number of
      target promoters and genes for TF families has increased dramatically. There are
      11,660 target genes (7479 in human, 2691 in mouse and 1490 in rat) and 14,908
      target promoters (10,225 in human, 2985 in mouse and 1698 in rat). Additionally,
      we constructed GRNs for each TF family by connecting the TF-target gene pairs.
      Such interaction data between TFs and their target genes will assist detailed
      functional studies and help to obtain a panoramic view of the GRNs for cancer
      research.

PMID- 17202160
TI  - PolyA_DB 2: mRNA polyadenylation sites in vertebrate genes.
AB  - Polyadenylation of nascent transcripts is one of the key mRNA processing events
      in eukaryotic cells. A large number of human and mouse genes have alternative
      polyadenylation sites, or poly(A) sites, leading to mRNA variants with different
      protein products and/or 3'-untranslated regions (3'-UTRs). PolyA_DB 2 contains
      poly(A) sites identified for genes in several vertebrate species, including
      human, mouse, rat, chicken and zebrafish, using alignments between cDNA/ESTs and
      genome sequences. Several new features have been added to the database since its
      last release, including syntenic genome regions for human poly(A) sites in seven
      other vertebrates and cis-element information adjacent to poly(A) sites. Trace
      sequences are used to provide additional evidence for poly(A/T) tails in
      cDNA/ESTs. The updated database is intended to broaden poly(A) site coverage in
      vertebrate genomes, and provide means to assess the authenticity of poly(A) sites
      identified by bioinformatics. The URL for this database is
      http://polya.umdnj.edu/PolyA_DB2.

PMID- 17202161
TI  - GenBank.
AB  - GenBank (R) is a comprehensive database that contains publicly available
      nucleotide sequences for more than 240 000 named organisms, obtained primarily
      through submissions from individual laboratories and batch submissions from large
      scale sequencing projects. Most submissions are made using the web-based BankIt
      or standalone Sequin programs and accession numbers are assigned by GenBank staff
      upon receipt. Daily data exchange with the EMBL Data Library in Europe and the
      DNA Data Bank of Japan ensures worldwide coverage. GenBank is accessible through
      NCBI's retrieval system, Entrez, which integrates data from the major DNA and
      protein sequence databases along with taxonomy, genome, mapping, protein
      structure and domain information, and the biomedical journal literature via
      PubMed. BLAST provides sequence similarity searches of GenBank and other sequence
      databases. Complete bimonthly releases and daily updates of the GenBank database
      are available by FTP. To access GenBank and its related retrieval and analysis
      services, begin at the NCBI Homepage (www.ncbi.nlm.nih.gov).

PMID- 17202163
TI  - REBASE--enzymes and genes for DNA restriction and modification.
AB  - REBASE is a comprehensive database of information about restriction enzymes, DNA
      methyltransferases and related proteins involved in the biological process of
      restriction-modification. It contains fully referenced information about
      recognition and cleavage sites, isoschizomers, neoschizomers, commercial
      availability, methylation sensitivity, crystal and sequence data. Experimentally
      characterized homing endonucleases are also included. All newly sequenced genomes
      are analyzed for the presence of putative restriction systems and these data are
      included within the REBASE. The contents or REBASE may be browsed from the web
      (http://rebase.neb.com/rebase/rebase.ftp.html) and selected compilations can be
      downloaded by ftp (ftp.neb.com). Additionally, monthly updates can be requested
      via email.

PMID- 17202162
TI  - New developments in the InterPro database.
AB  - InterPro is an integrated resource for protein families, domains and functional
      sites, which integrates the following protein signature databases: PROSITE,
      PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER.
      The latter two new member databases have been integrated since the last
      publication in this journal. There have been several new developments in
      InterPro, including an additional reading field, new database links, extensions
      to the web interface and additional match XML files. InterPro has always provided
      matches to UniProtKB proteins on the website and in the match XML file on the FTP
      site. Additional matches to proteins in UniParc (UniProt archive) are now
      available for download in the new match XML files only. The latest InterPro
      release (13.0) contains more than 13 000 entries, covering over 78% of all
      proteins in UniProtKB. The database is available for text- and sequence-based
      searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by
      anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan
      search tool is now also available via a web service at
      http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.

PMID- 17202164
TI  - Sharing of worldwide distributed carbohydrate-related digital resources: online
      connection of the Bacterial Carbohydrate Structure DataBase and GLYCOSCIENCES.de.
AB  - Functional glycomics, the scientific attempt to identify and assign functions to
      all glycan molecules synthesized by an organism, is an emerging field of science.
      In recent years, several databases have been started, all aiming to support
      deciphering the biological function of carbohydrates. However, diverse encoding
      and storage schemes are in use amongst these databases, significantly hampering
      the interchange of data. The mutual online access between the Bacterial
      Carbohydrate Structure DataBase (BCSDB) and the GLYCOSCIENCES.de portal, as a
      first reported attempt of a structure-based direct interconnection of two glyco
      related databases is described. In this approach, users have to learn only one
      interface, will always have access to the latest data of both services, and will
      have the results of both searches presented in a consistent way. The
      establishment of this connection helped to find shortcomings and inconsistencies
      in the database design and functionality related to underlying data concepts and
      structural representations. For the maintenance of the databases, duplication of
      work can be easily avoided, and will hopefully lead to a better worldwide
      acceptance of both services within the community of glycoscienists. BCSDB is
      available at http://www.glyco.ac.ru/bcsdb/ and the GLYCOSCIENCES.de portal at
      http://www.glycosciences.de/.

PMID- 17202165
TI  - TBestDB: a taxonomically broad database of expressed sequence tags (ESTs).
AB  - The TBestDB database contains approximately 370,000 clustered expressed sequence
      tag (EST) sequences from 49 organisms, covering a taxonomically broad range of
      poorly studied, mainly unicellular eukaryotes, and includes experimental
      information, consensus sequences, gene annotations and metabolic pathway
      predictions. Most of these ESTs have been generated by the Protist EST Program, a
      collaboration among six Canadian research groups. EST sequences are read from
      trace files up to a minimum quality cut-off, vector and linker sequence is
      masked, and the ESTs are clustered using phrap. The resulting consensus sequences
      are automatically annotated by using the AutoFACT program. The datasets are
      automatically checked for clustering errors due to chimerism and potential cross
      contamination between organisms, and suspect data are flagged in or removed from
      the database. Access to data deposited in TBestDB by individual users can be
      restricted to those users for a limited period. With this first report on
      TBestDB, we open the database to the research community for free processing,
      annotation, interspecies comparisons and GenBank submission of EST data generated
      in individual laboratories. For instructions on submission to TBestDB, contact
      tbestdb@bch.umontreal.ca. The database can be queried at
      http://tbestdb.bcm.umontreal.ca/.

PMID- 17202166
TI  - DroSpeGe: rapid access database for new Drosophila species genomes.
AB  - The Drosophila species comparative genome database DroSpeGe
      (http://insects.eugenes.org/DroSpeGe/) provides genome researchers with rapid,
      usable access to 12 new and old Drosophila genomes, since its inception in 2004.
      Scientists can use, with minimal computing expertise, the wealth of new genome
      information for developing new insights into insect evolution. New genome
      assemblies provided by several sequencing centers have been annotated with known
      model organism gene homologies and gene predictions to provided basic comparative
      data. TeraGrid supplies the shared cyberinfrastructure for the primary
      computations. This genome database includes homologies to Drosophila melanogaster
      and eight other eukaryote model genomes, and gene predictions from several
      groups. BLAST searches of the newest assemblies are integrated with genome maps.
      GBrowse maps provide detailed views of cross-species aligned genomes. BioMart
      provides for data mining of annotations and sequences. Common chromosome maps
      identify major synteny among species. Potential gain and loss of genes is
      suggested by Gene Ontology groupings for genes of the new species. Summaries of
      essential genome statistics include sizes, genes found and predicted, homology
      among genomes, phylogenetic trees of species and comparisons of several gene
      predictions for sensitivity and specificity in finding new and known genes.

PMID- 17202167
TI  - BRENDA, AMENDA and FRENDA: the enzyme information system in 2007.
AB  - The BRENDA (BRaunschweig ENzyme DAtabase) enzyme information system
      (http://www.brenda.uni-koeln.de) is the largest publicly available enzyme
      information system worldwide. The major parts of its contents are manually
      extracted from primary literature. It is not restricted to specific groups of
      enzymes, but includes information on all identified enzymes irrespective of the
      enzyme's source. The range of data encompasses functional, structural, sequence,
      localisation, disease-related, isolation, stability information on enzyme and
      ligand-related data. Each single entry is linked to the enzyme source and to a
      literature reference. Recently the data repository was complemented by text
      mining data in AMENDA (Automatic Mining of ENzyme DAta) and FRENDA (Full
      Reference ENzyme DAta). A genome browser, membrane protein prediction and full
      text search capacities were added. The newly implemented web service provides
      instant access to the data for programmers via a SOAP (Simple Object Access
      Protocol) interface. The BRENDA data can be downloaded in the form of a text file
      from the beginning of 2007.

PMID- 17202169
TI  - SYSTOMONAS--an integrated database for systems biology analysis of Pseudomonas.
AB  - To provide an integrated bioinformatics platform for a systems biology approach
      to the biology of pseudomonads in infection and biotechnology the database
      SYSTOMONAS (SYSTems biology of pseudOMONAS) was established. Besides our own
      experimental metabolome, proteome and transcriptome data, various additional
      predictions of cellular processes, such as gene-regulatory networks were stored.
      Reconstruction of metabolic networks in SYSTOMONAS was achieved via comparative
      genomics. Broad data integration is realized using SOAP interfaces for the well
      established databases BRENDA, KEGG and PRODORIC. Several tools for the analysis
      of stored data and for the visualization of the corresponding results are
      provided, enabling a quick understanding of metabolic pathways, genomic
      arrangements or promoter structures of interest. The focus of SYSTOMONAS is on
      pseudomonads and in particular Pseudomonas aeruginosa, an opportunistic human
      pathogen. With this database we would like to encourage the Pseudomonas community
      to elucidate cellular processes of interest using an integrated systems biology
      strategy. The database is accessible at http://www.systomonas.de.

PMID- 17202168
TI  - HMDB: the Human Metabolome Database.
AB  - The Human Metabolome Database (HMDB) is currently the most complete and
      comprehensive curated collection of human metabolite and human metabolism data in
      the world. It contains records for more than 2180 endogenous metabolites with
      information gathered from thousands of books, journal articles and electronic
      databases. In addition to its comprehensive literature-derived data, the HMDB
      also contains an extensive collection of experimental metabolite concentration
      data compiled from hundreds of mass spectra (MS) and Nuclear Magnetic resonance
      (NMR) metabolomic analyses performed on urine, blood and cerebrospinal fluid
      samples. This is further supplemented with thousands of NMR and MS spectra
      collected on purified, reference metabolites. Each metabolite entry in the HMDB
      contains an average of 90 separate data fields including a comprehensive compound
      description, names and synonyms, structural information, physico-chemical data,
      reference NMR and MS spectra, biofluid concentrations, disease associations,
      pathway information, enzyme data, gene sequence data, SNP and mutation data as
      well as extensive links to images, references and other public databases.
      Extensive searching, relational querying and data browsing tools are also
      provided. The HMDB is designed to address the broad needs of biochemists,
      clinical chemists, physicians, medical geneticists, nutritionists and members of
      the metabolomics community. The HMDB is available at: www.hmdb.ca.

PMID- 17202170
TI  - CYCLONET--an integrated database on cell cycle regulation and carcinogenesis.
AB  - Computational modelling of mammalian cell cycle regulation is a challenging task,
      which requires comprehensive knowledge on many interrelated processes in the
      cell. We have developed a web-based integrated database on cell cycle regulation
      in mammals in normal and pathological states (Cyclonet database). It integrates
      data obtained by 'omics' sciences and chemoinformatics on the basis of systems
      biology approach. Cyclonet is a specialized resource, which enables researchers
      working in the field of anticancer drug discovery to analyze the wealth of
      currently available information in a systematic way. Cyclonet contains
      information on relevant genes and molecules; diagrams and models of cell cycle
      regulation and results of their simulation; microarray data on cell cycle and on
      various types of cancer, information on drug targets and their ligands, as well
      as extensive bibliography on modelling of cell cycle and cancer-related gene
      expression data. The Cyclonet database is also accessible through the BioUML
      workbench, which allows flexible querying, analyzing and editing the data by
      means of visual modelling. Cyclonet aims to predict promising anticancer targets
      and their agents by application of Prediction of Activity Spectra for Substances.
      The Cyclonet database is available at http://cyclonet.biouml.org.

PMID- 17202171
TI  - SNAPPI-DB: a database and API of Structures, iNterfaces and Alignments for
      Protein-Protein Interactions.
AB  - SNAPPI-DB, a high performance database of Structures, iNterfaces and Alignments
      of Protein-Protein Interactions, and its associated Java Application Programming
      Interface (API) is described. SNAPPI-DB contains structural data, down to the
      level of atom co-ordinates, for each structure in the Protein Data Bank (PDB)
      together with associated data including SCOP, CATH, Pfam, SWISSPROT, InterPro, GO
      terms, Protein Quaternary Structures (PQS) and secondary structure information.
      Domain-domain interactions are stored for multiple domain definitions and are
      classified by their Superfamily/Family pair and interaction interface. Each set
      of classified domain-domain interactions has an associated multiple structure
      alignment for each partner. The API facilitates data access via PDB entries,
      domains and domain-domain interactions. Rapid development, fast database access
      and the ability to perform advanced queries without the requirement for complex
      SQL statements are provided via an object oriented database and the Java Data
      Objects (JDO) API. SNAPPI-DB contains many features which are not available in
      other databases of structural protein-protein interactions. It has been applied
      in three studies on the properties of protein-protein interactions and is
      currently being employed to train a protein-protein interaction predictor and a
      functional residue predictor. The database, API and manual are available for
      download at: http://www.compbio.dundee.ac.uk/SNAPPI/downloads.jsp.

PMID- 17202172
TI  - SNPSTR: a database of compound microsatellite-SNP markers.
AB  - There has been widespread and growing interest in genetic markers suitable for
      drawing population genetic inferences about past demographic events and to detect
      the effects of selection. In addition to single nucleotide polymorphisms (SNPs),
      microsatellites (or short tandem repeats, STRs) have received great attention in
      the analysis of human population history. In the SNPSTR database
      (http://www.imperial.ac.uk/theoreticalgenomics/data-software) we catalogue a
      relatively new type of compound genetic marker called SNPSTR which combines a
      microsatellite marker (STR) with one or more tightly linked SNPs. Here, the
      SNP(s) and the microsatellite are less than 250 bp apart so each SNPSTR can be
      considered a small haplotype with no recombination occurring between the two
      individual markers. Thus, SNPSTRs have the potential to become a very useful tool
      in the field of population genetics. The SNPSTR database contains all inferable
      human SNPSTRs as well as those in mouse, rat, dog and chicken, i.e. all model
      organisms for which extensive SNP datasets are available.

PMID- 17202173
TI  - MIPSPlantsDB--plant database resource for integrative and comparative plant
      genome research.
AB  - Genome-oriented plant research delivers rapidly increasing amount of plant genome
      data. Comprehensive and structured information resources are required to
      structure and communicate genome and associated analytical data for model
      organisms as well as for crops. The increase in available plant genomic data
      enables powerful comparative analysis and integrative approaches. PlantsDB aims
      to provide data and information resources for individual plant species and in
      addition to build a platform for integrative and comparative plant genome
      research. PlantsDB is constituted from genome databases for Arabidopsis,
      Medicago, Lotus, rice, maize and tomato. Complementary data resources for cis
      elements, repetive elements and extensive cross-species comparisons are
      implemented. The PlantsDB portal can be reached at
      http://mips.gsf.de/projects/plants.

PMID- 17202175
TI  - GlycoMapsDB: a database of the accessible conformational space of glycosidic
      linkages.
AB  - Conformational energy maps of the glycosidic linkages are a valuable resource to
      gain information about preferred conformations and flexibility of carbohydrates.
      Here we present GlycoMapsDB, a new database containing more than 2500 calculated
      conformational maps for a variety of di- to pentasaccharide fragments contained
      in N- and O-glycans. Oligosaccharides representing branchpoints of N-glycans are
      included in the set of fragments, thus the influence of neighbouring residues is
      reflected in the conformational maps. During refinement of new crystal
      structures, maps contained in GlycoMapsDB can serve as a valuable resource to
      check whether the torsion values of a glycosidic linkage are located in an
      'allowed' region similar to the Ramachandran plot analysis for proteins. This
      might help to improve the structural quality of the glycan data contained in the
      Protein Data Bank (PDB). A link between GlycoMapsDB and the PDB has been
      established so that the glycosidic torsions of all glycans contained in the PDB
      can be retrieved and compared to calculated data. The service is available at
      www.glycosciences.de/modeling/glycomapsdb/.

PMID- 17202174
TI  - MaizeGDB's new data types, resources and activities.
AB  - MaizeGDB is the Maize Genetics and Genomics Database. Available at MaizeGDB are
      diverse data that support maize research including maps, gene product
      information, loci and their various alleles, phenotypes (both naturally occurring
      and as a result of directed mutagenesis), stocks, sequences, molecular markers,
      references and contact information for maize researchers worldwide. Also
      available through MaizeGDB are various community support service bulletin boards
      including the Editorial Board's list of high-impact papers, information about the
      Annual Maize Genetics Conference and the Jobs board where employment
      opportunities are posted. Reported here are data updates, improvements to
      interfaces and changes to standard operating procedures that have been made
      during the past 2 years. MaizeGDB is freely available and can be accessed online
      at http://www.maizegdb.org.

PMID- 17202178
TI  - Heart conduction disorders related to antimalarials toxicity: an analysis of
      electrocardiograms in 85 patients treated with hydroxychloroquine for connective
      tissue diseases.
AB  - OBJECTIVE: The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ)
      are used in long-term treatment of connective tissue diseases (CTDs). A high
      incidence of heart conduction disorders, including bundle-branch block and
      incomplete or complete atrioventricular block, has been observed among patients
      treated with CQ. Since no data were available for HCQ, we studied
      electrocardiograms (ECGs) in 85 unselected patients with CTD treated with HCQ as
      the sole antimalarial. METHODS: Eighty-five unselected out-patients treated with
      HCQ for a minimum of 1 yr, and without established cardiac diseases had standard
      12-lead ECGs. RESULTS: Two incomplete right bundle-branch blocks and one left
      bundle-branch block were observed. No atrioventricular block was observed. The
      mean PR interval was 137 +/- 20 ms (range 99-188). The mean QTc interval was 410
      ms (range 349-464). The mean heart rate was 73 beats/min (range 53-102).
      CONCLUSION: PR interval, QTc interval and heart rate were not different from
      normal values. The rate of heart conduction disorders was similar to what is
      expected in the general population, and contrasted with prior results in CQ
      treated patients. Our results add further evidence on the safety of HCQ compared
      with CQ.

PMID- 17202177
TI  - Down-regulation of leucocyte immunoglobulin-like receptor expression in the
      synovium of rheumatoid arthritis patients after treatment with disease-modifying
      anti-rheumatic drugs.
AB  - OBJECTIVES: To compare the expression of leucocyte immunoglobulin-like receptors
      (LILRs) also known as ILTs and LIRs in rheumatoid arthritis (RA) synovial
      membrane before and after treatment with disease-modifying anti-rheumatic drugs
      (DMARDs) and investigate regulation of LILR-expression and function in vitro.
      METHODS: A study was performed on serial synovial biopsies obtained from 10 RA
      patients before and after treatment with DMARDs. Expression of the activating
      LILRA2 (ILT1 or LIR-7) and inhibitory LILRB2 (ILT4 or LIR-2) and LILRB3 (ILT5 or
      LIR-3) was evaluated by immunohistochemical staining, and quantified by a
      validated scoring system. Peripheral blood mononuclear cells and in vitro derived
      macrophages were used to determine effects of DMARDs on expression and function
      of LILRs. RESULTS: Abundant expression of LILRB2, B3 and A2 was found in synovial
      tissue of all patients before treatment. Number of inflammatory cells expressing
      both inhibitory and activating LILRs dramatically decreased in patients who
      responded to treatment, but remained high in those who did not. However,
      treatment of macrophages with DMARDs in vitro did not down-regulate LILR
      expression. On the other hand, reduction in LILR expression in RA synovia was
      associated with decreased inflammatory infiltrates in those who responded to
      treatment. Cross-linking of LILRA2 on macrophages caused substantial production
      of tumour necrosis factor (TNF-alpha) in a dose- and time-dependent manner that
      was strongly inhibited by dexamethasone. CONCLUSIONS: We show that expression of
      LILRs in RA synovium was significantly reduced only in patients who responded to
      treatment. However, clinical responses may not be due to direct effects of DMARDs
      on LILR expression but due to partial inhibition of LIRA2-mediated TNF-alpha
      production by steroids leading to suppression of inflammation.

PMID- 17202179
TI  - Induction of a high-CO2-inducible, periplasmic protein, H43, and its application
      as a high-CO2-responsive marker for study of the high-CO2-sensing mechanism in
      Chlamydomonas reinhardtii.
AB  - The unicellular green alga Chlamydomonas reinhardtii can acclimate to a broad
      range of environmental CO(2) concentrations. We observed that the cells
      synthesized a specific 43 kDa protein, H43, in the periplasmic space under
      photoautotrophic high-CO(2) conditions. Under low-CO(2) conditions, H43
      disappeared. However, H43 mRNA expression was observed even under heterotrophic
      low-CO(2) conditions when the cells were grown with 17.4 mM acetate in darkness.
      When the cells were treated with 4,4'-dithiocyanatostilbene-2,2'-disulfonate
      (DIDS) and mersalyl to modify cell surface proteins, H43 mRNA expression was
      strongly affected under both heterotrophic and photoautotrophic conditions. The
      H43 induction pattern in a mitochondrial respiration-deficient mutant dum-1 that
      lacks cytochrome c oxidase was the same, but the level was much lower than that
      in the wild type. Even under illumination, the dissolved CO(2) concentration in
      the culture rapidly increased slightly following the addition of acetate and
      dramatically increased even further by the inhibition of photosynthesis with
      DCMU. Radiotracer experiments with [U-(14)C]acetate revealed that (14)CO(2)
      release from cells was greater in darkness than in the light due to the great
      stimulation of internal CO(2) evolution, resulting in an increase in external
      CO(2) concentration. Strong light inhibited H43 induction and DCMU promoted the
      induction under photoheterotrophic low-CO(2) conditions. The results demonstrate
      that H43 is strictly regulated by a concentration of CO(2) resulting from
      respiration and photosynthesis. Our results suggest that Chlamydomonas induces
      high-CO(2)-responsive protein H43 by sensing the concentration of ambient CO(2)
      with the contribution of cell surface protein.

PMID- 17202180
TI  - AHK5 histidine kinase regulates root elongation through an ETR1-dependent
      abscisic acid and ethylene signaling pathway in Arabidopsis thaliana.
AB  - The Arabidopsis thaliana genome encodes a small family of histidine (His) protein
      kinases, some of which have redundant functions as ethylene receptors, whereas
      others serve as cytokinin receptors. The most poorly characterized of these is
      authentic histidine kinase 5 (AHK5; also known as cytokinin-independent 2, CKI2).
      Here we characterize three independent ahk5 mutants, and show that they have a
      common phenotype. Our results suggest that AHK5 His-kinase acts as a negative
      regulator in the signaling pathway in which ethylene and ABA inhibit the root
      elongation through ETR1 (an ethylene receptor).

PMID- 17202181
TI  - Characterization of a splicing variant of plant Aurora kinase.
AB  - Aurora kinases play a key role in chromosome segregation and cytokinesis. In
      plants, three Aurora kinases (AtAUR1-AtAUR3) have been identified in Arabidopsis
      thaliana. Here, we report an AtAUR2 splicing variant (AtAUR2S), which lacks the
      fourth exon encoding a part of the kinase domain of AtAUR2. AtAUR2S was shown to
      have lost its kinase activity to phosphorylate histone H3 at Ser10; however, it
      maintained its ability to bind to histone H3. The localization pattern of AtAUR2S
      was the same as that of AtAUR2. The findings suggest that AtAUR2S affects cell
      division by competing with AtAUR2.

PMID- 17202182
TI  - ARR1 directly activates cytokinin response genes that encode proteins with
      diverse regulatory functions.
AB  - Plant cells respond to cytokinins by changing their gene expression patterns. The
      histidyl-aspartyl (His-Asp) phosphorelay mediates the signal from cytokinin
      receptors to type-B response regulators including ARR1, which transactivate
      cytokinin primary response genes. However, the overall architecture of the signal
      cascade leading to cytokinin-responsive phenomena is still unclear, mainly
      because it is not known how the His-Asp phosphorelay is connected to downstream
      phenomena. To reveal events immediately downstream from the phosphorelay-mediated
      transcriptional activation, we searched for direct-target genes of ARR1 by
      exploiting ARR1DeltaDDK-GR, a chimeric transcription factor that transactivates
      ARR1 direct-target genes in transgenic plants by glucocorticoid induction. We
      identified 23 direct-target genes, most of which were found to be cytokinin
      primary response genes. The arr1-1 mutation clearly affected the primary response
      in at least 17 genes, meaning that they respond primarily to cytokinins through
      the function of ARR1. The 17 genes encode proteins with diverse functions,
      including type-A response regulators, cytokinin metabolic enzymes and putative
      disease resistance response proteins. These results provide novel evidence
      indicating that the His-Asp phosphorelay is connected to diverse regulatory
      levels of cytokinin-responsive phenomena through ARR1 direct-target genes.

PMID- 17202183
TI  - Regulation of summer dormancy by water deficit and ABA in Poa bulbosa ecotypes.
AB  - BACKGROUND AND AIMS: Survival of many herbaceous species in Mediterranean
      habitats during the dry, hot summer depends on the induction of summer dormancy
      by changes in environmental conditions during the transition between the winter
      (growth) season to the summer (resting) season, i.e. longer days, increasing
      temperature and drought. In Poa bulbosa, a perennial geophytic grass, summer
      dormancy is induced by long days, and the induction is enhanced by high
      temperature. Here the induction of summer dormancy in a Mediterranean perennial
      grass by water deficit under non-inductive photoperiodic conditions is reported
      for the first time. METHODS: Plants grown under 22/16 degrees C and non-inductive
      short-day (9 h, SD) were subjected to water deficit (WD), applied as cycles of
      reduced irrigation, or sprayed with ABA solutions. They were compared with plants
      in which dormancy was induced by transfer from SD to inductive long-day (16 h,
      LD). Responses of two contrasting ecotypes, from arid and mesic habitats were
      compared. Dormancy relaxation in bulbs from these ecotypes and treatments was
      studied by comparing sprouting capacity in a wet substrate at 10 degrees C of
      freshly harvested bulbs to that of dry-stored bulbs at 40 degrees C. Endogenous
      ABA in the bulbs was determined by monoclonal immunoassay analysis. KEY RESULTS:
      Dormancy was induced by WD and by ABA application in plants growing under non
      inductive SD. Dormancy induction by WD was associated with increased levels of
      ABA. Bulbs were initially deeply dormant and their sprouting capacity was very
      low, as in plants in which dormancy was induced by LD. Dormancy was released
      after 2 months dry storage at 40 degrees C in all treatments. ABA levels were not
      affected by dormancy relaxation. CONCLUSIONS: Summer dormancy in P. bulbosa can
      be induced by two alternative and probably additive pathways: (1) photoperiodic
      induction by long-days, and (2) water deficit. Increased levels of endogenous ABA
      are involved in both pathways.

PMID- 17202184
TI  - Mating system of Brazilian Oryza glumaepatula populations studied with
      microsatellite markers.
AB  - BACKGROUND AND AIMS: A knowledge of natural populations' breeding systems is
      important in order to implement in situ and ex situ management and conservation
      practices. Using microsatellite markers, three Oryza glumaepatula populations
      from Brazil were studied to determine the breeding system and genetic structure
      parameters of this species. METHODS: Each population represented by ten families
      with ten individuals per family was studied using eight microsatellite primers.
      Families of the Rio Xingu population (XI) were obtained from the greenhouse,
      whereas families from Rio Solimoes (SO) and Rio Paraguay (PG) were collected from
      the wild. Amplified products electrophoresed on non-denaturing polyacrylamide
      gels were visualized with a silver staining procedure. The mating system
      parameters were analysed based on the mixed mating model (software MLTR) while
      genetic structure analyses of the three populations and their families were
      performed using the FSTAT software. KEY RESULTS: The mean numbers of alleles per
      loci were 2.5, 3.9 and 2.5, respectively for the XI, PG and SO populations.
      Compared with their families, higher values for the observed heterozygosity and
      gene diversity were estimated for the parental populations. The subdivision
      (based on R(ST)) and inbreeding (F(IS)) in the SO and PG populations had similar
      effects, while inbreeding was the main effect in the families. Multilocus
      outcrossing rates varied from 0.011 to 0.223 in the three populations, indicating
      divergence in the outcrossing rates among O. glumaepatula populations. For the
      species (considering SO and PG populations together) an intermediate value was
      observed (tm = 0.116). Biparental inbreeding varied from 0.008 to 0.123,
      contributing to the selfing rate in these populations. More than 50 % of the
      outcrossing occurred between related individuals. CONCLUSIONS: The results
      indicated divergence in the mating system among O. glumaepatula populations, with
      consequences for conservation practices. The mating system of this species was
      classified as mixed with a predominance of self-fertilization.

PMID- 17202186
TI  - Nkx2.2-repressor activity is sufficient to specify alpha-cells and a small number
      of beta-cells in the pancreatic islet.
AB  - The homeodomain protein Nkx2.2 (Nkx2-2) is a key regulator of pancreatic islet
      cell specification in mice; Nkx2.2 is essential for the differentiation of all
      insulin-producing beta-cells and of the majority of glucagon-producing alpha
      cells, and, in its absence, these cell types are converted to a ghrelin cell
      fate. To understand the molecular functions of Nkx2.2 that regulate these early
      cell-fate decisions during pancreatic islet development, we created Nkx2.2
      dominant-derivative transgenic mice. In the absence of endogenous Nkx2.2, the
      Nkx2.2-Engrailed-repressor derivative is sufficient to fully rescue glucagon
      producing alpha-cells and to partially rescue insulin-producing beta-cells.
      Interestingly, the insulin-positive cells that do form in the rescued mice do not
      express the mature beta-cell markers MafA or Glut2 (Slc2a2), suggesting that
      additional activator functions of Nkx2.2 are required for beta-cell maturation.
      To explore the mechanism by which Nkx2.2 functions as a repressor in the islet,
      we assessed the pancreatic expression of the Groucho co-repressors, Grg1, Grg2,
      Grg3 and Grg4 (Tle1-Tle4), which have been shown to interact with and modulate
      Nkx2.2 function. We determined that Grg3 is highly expressed in the embryonic
      pancreas in a pattern similar to Nkx2.2. Furthermore, we show that Grg3
      physically interacts with Nkx2.2 through its TN domain. These studies suggest
      that Nkx2.2 functions predominantly as a transcriptional repressor during
      specification of endocrine cell types in the pancreas.

PMID- 17202185
TI  - Controlled overexpression of Pax6 in vivo negatively autoregulates the Pax6
      locus, causing cell-autonomous defects of late cortical progenitor proliferation
      with little effect on cortical arealization.
AB  - Levels of expression of the transcription factor Pax6 vary throughout
      corticogenesis in a rostro-lateral(high) to caudo-medial(low) gradient across the
      cortical proliferative zone. Previous loss-of-function studies have indicated
      that Pax6 is required for normal cortical progenitor proliferation, neuronal
      differentiation, cortical lamination and cortical arealization, but whether and
      how its level of expression affects its function is unclear. We studied the
      developing cortex of PAX77 YAC transgenic mice carrying several copies of the
      human PAX6 locus with its full complement of regulatory regions. We found that
      PAX77 embryos express Pax6 in a normal spatial pattern, with levels up to three
      times higher than wild type. By crossing PAX77 mice with a new YAC transgenic
      line that reports Pax6 expression (DTy54), we showed that increased expression is
      limited by negative autoregulation. Increased expression reduces proliferation of
      late cortical progenitors specifically, and analysis of PAX77<---->wild-type
      chimeras indicates that the defect is cell autonomous. We analyzed cortical
      arealization in PAX77 mice and found that, whereas the loss of Pax6 shifts caudal
      cortical areas rostrally, Pax6 overexpression at levels predicted to shift
      rostral areas caudally has very little effect. These findings indicate that Pax6
      levels are stabilized by autoregulation, that the proliferation of cortical
      progenitors is sensitive to altered Pax6 levels and that cortical arealization is
      not.

PMID- 17202187
TI  - Abelson kinase (Abl) and RhoGEF2 regulate actin organization during cell
      constriction in Drosophila.
AB  - Morphogenesis involves the interplay of different cytoskeletal regulators.
      Investigating how they interact during a given morphogenetic event will help us
      understand animal development. Studies of ventral furrow formation, a
      morphogenetic event during Drosophila gastrulation, have identified a signaling
      pathway involving the G-protein Concertina (Cta) and the Rho activator RhoGEF2.
      Although these regulators act to promote stable myosin accumulation and apical
      cell constriction, loss-of-function phenotypes for each of these pathway members
      is not equivalent, suggesting the existence of additional ventral furrow
      regulators. Here, we report the identification of Abelson kinase (Abl) as a novel
      ventral furrow regulator. We find that Abl acts apically to suppress the
      accumulation of both Enabled (Ena) and actin in mesodermal cells during ventral
      furrow formation. Further, RhoGEF2 also regulates ordered actin localization
      during ventral furrow formation, whereas its activator, Cta, does not. Taken
      together, our data suggest that there are two crucial preconditions for apical
      constriction in the ventral furrow: myosin stabilization/activation, regulated by
      Cta and RhoGEF2; and the organization of apical actin, regulated by Abl and
      RhoGEF2. These observations identify an important morphogenetic role for Abl and
      suggest a conserved mechanism for this kinase during apical cell constriction.

PMID- 17202188
TI  - The mouse seminal vesicle shape mutation is allelic with Fgfr2.
AB  - The mouse seminal vesicle shape (svs) mutation is a spontaneous recessive
      mutation that causes branching morphogenesis defects in the prostate gland and
      seminal vesicles. Unlike many other mutations that reduce prostatic and/or
      seminal vesicle branching, the svs mutation dramatically reduces branching
      without reducing organ growth. Using a positional cloning approach, we identified
      the svs mutant lesion as a 491 bp insertion in the tenth intron of Fgfr2 that
      results in changes in the pattern of Fgfr2 alternative splicing. An engineered
      null allele of Fgfr2 failed to complement the svs mutation proving that a partial
      loss of FGFR2(IIIb) isoforms causes svs phenotypes. Thus, the svs mutation
      represents a new type of adult viable Fgfr2 allele that can be used to elucidate
      receptor function during normal development and in the adult. In the developing
      seminal vesicles, sustained activation of ERK1/2 was associated with branching
      morphogenesis and this was absent in svs mutant seminal vesicles. This defect
      appears to be the immediate downstream effect of partial loss of FGFR2(IIIb)
      because activation of FGFR2(IIIb) by FGF10 rapidly induced ERK1/2 activation, and
      inhibition of ERK1/2 activation blocked seminal vesicle branching morphogenesis.
      Partial loss of FGFR2(IIIb) was also associated with down-regulation of several
      branching morphogenesis regulators including Shh, Ptch1, Gli1, Gli2, Bmp4, and
      Bmp7. Together with previous studies, these data suggest that peak levels of
      FGFR2(IIIb) signaling are required to induce branching and sustain ERK1/2
      activation, whereas reduced levels support ductal outgrowth in the prostate gland
      and seminal vesicles.

PMID- 17202189
TI  - Wnt11/beta-catenin signaling in both oocytes and early embryos acts through LRP6
      mediated regulation of axin.
AB  - Current models of canonical Wnt signaling assume that a pathway is active if beta
      catenin becomes nuclearly localized and Wnt target genes are transcribed. We show
      that, in Xenopus, maternal LRP6 is essential in such a pathway, playing a pivotal
      role in causing expression of the organizer genes siamois and Xnr3, and in
      establishing the dorsal axis. We provide evidence that LRP6 acts by degrading
      axin protein during the early cleavage stage of development. In the full-grown
      oocyte, before maturation, we find that axin levels are also regulated by Wnt11
      and LRP6. In the oocyte, Wnt11 and/or LRP6 regulates axin to maintain beta
      catenin at a low level, while in the embryo, asymmetrical Wnt11/LRP6 signaling
      stabilizes beta-catenin and enriches it on the dorsal side. This suggests that
      canonical Wnt signaling may not exist in simple off or on states, but may also
      include a third, steady-state, modality.

PMID- 17202190
TI  - Molecular analysis of coordinated bladder and urogenital organ formation by
      Hedgehog signaling.
AB  - The urogenital and reproductive organs, including the external genitalia, bladder
      and urethra, develop as anatomically aligned organs. Descriptive and experimental
      embryology suggest that the cloaca, and its derivative, the urogenital sinus,
      contribute to the formation of these organs. However, it is unknown how the
      primary tissue lineages in, and adjacent to, the cloaca give rise to the above
      organs, nor is bladder formation understood. While it is known that sonic
      hedgehog (Shh) is expressed by the cloacal epithelia, the developmental programs
      that regulate and coordinate the formation of the urogenital and reproductive
      organs have not been elucidated. Here we report that Shh mutant embryos display
      hypoplasia of external genitalia, internal urethra (pelvic urethra) and bladder.
      The importance of Shh signaling in the development of bladder and external
      genitalia was confirmed by analyzing a variety of mutant mouse lines with
      defective hedgehog signaling. By genetically labeling hedgehog-responding tissue
      lineages adjacent to the cloaca and urogenital sinus, we defined the contribution
      of these tissues to the bladder and external genitalia. We discovered that
      development of smooth muscle myosin-positive embryonic bladder mesenchyme
      requires Shh signaling, and that the bladder mesenchyme and dorsal (upper)
      external genitalia derive from Shh-responsive peri-cloacal mesenchyme. Thus, the
      mesenchymal precursors for multiple urogenital structures derive from peri
      cloacal mesenchyme and the coordination of urogenital organ formation from these
      precursors is orchestrated by Shh signals.

PMID- 17202191
TI  - RNA recognition mechanism of the minimal active domain of the human
      immunodeficiency virus type-2 nucleocapsid protein.
AB  - NCp8 of HIV-2 contains two CCHC-type zinc fingers connected by a linker, and is
      involved in many critical steps of the virus life cycle. It was previously shown
      that the first zinc finger flanked by the linker is the minimal active domain for
      specific binding to viral RNA. In our previous study, we determined the three
      dimensional structure of NCp8-f1, including the minimal active domain, and found
      that a hydrogen bond between Asn(11) N(delta)H and Arg(27) O stabilized the
      conformation of the linker in the vicinity of the zinc finger [Kodera et al.
      (1998) Biochemistry 37, 17704-17713]. In this study, RNA binding activities of
      NCp8-f1 and three types of its mutant peptides were analysed by native PAGE
      assay. The activity and three-dimensional structure of NCp8-f1/N11A, in which
      alanine is substituted for Asn(11) thereby affecting the conformation of the
      linker, was analyzed and compared with those of NCp8-f1. We demonstrated that the
      existence of Arg(4) and/or Lys(5) and Arg(26) and/or Arg(27) were necessary for
      binding RNA. Furthermore, the linker's flexible orientation, which is controlled
      by the hydrogen bond between Asn(11) N(delta)H and Arg(27) O, appears to be a
      structural basis for NCp8 existing as a multi-functional protein.

PMID- 17202192
TI  - Site-selective post-translational modification of proteins using an unnatural
      amino acid, 3-azidotyrosine.
AB  - An efficient method for site-selective modification of proteins using an
      unnatural amino acid, 3-azidotyrosine has been developed. This method utilizes
      the yeast amber suppressor tRNA(Tyr)/mutated tyrosyl-tRNA synthetase pair as a
      carrier of 3-azidotyrosine in an Escherichia coli cell-free translation system,
      and triarylphosphine derivatives for specific modification of the azido group.
      Using rat calmodulin (CaM) as a model protein, we prepared several unnatural CaM
      molecules, each carrying an azidotyrosine at predetermined positions 72, 78, 80
      or 100, respectively. Post-translational modification of these proteins with a
      conjugate compound of triarylphosphine and biotin produced site-selectively
      biotinylated CaM molecules. Reaction efficiency was similar among these proteins
      irrespective of the position of introduction, and site-specificity of
      biotinylation was confirmed using mass spectrometry. In addition, CBP-binding
      activity of the biotinylated CaMs was confirmed to be similar to that of wild
      type CaM. This method is intrinsically versatile in that it should be easily
      applicable to introducing any other desirable compounds (e.g., probes and cross
      linkers) into selected sites of proteins as far as appropriate derivative
      compounds of triarylphosphine could be chemically synthesized. Elucidation of
      molecular mechanisms of protein functions and protein-to-protein networks will be
      greatly facilitated by making use of these site-selectively modified proteins.

PMID- 17202193
TI  - Augmented chemosensitivity in black-eyed white Mitfmi-bw mice, lacking
      melanocytes.
AB  - Microphthalmia-associated transcription factor (Mitf) is responsible for
      differentiation of melanocytes, and a recessive Mitf mutant, black-eyed white
      (bw) mouse, is characterized by the lack of melanocytes in the skin and inner
      ear. To search for the hitherto unknown roles of melanocytes, we analysed the
      ventilatory responses of unanaesthetized bw mice by whole body plethysmography.
      During air breathing, bw mice showed lower breathing frequency and larger tidal
      volume, compared with age-matched wild-type mice, although there was no
      difference in the minute ventilation. Importantly, bw mice present normal
      haematocrit values and red blood cell counts. We next measured the immediate
      ventilatory responses to acute hypoxia (10% O2) and to hyperoxic hypercapnia (10%
      CO2). Hypoxic and hypercapnic ventilatory responses represent the functions of
      the chemoreceptors in the carotid body and the brainstem, respectively. The bw
      mice retain the peripheral hypoxic and central hypercapnic sensing functions, but
      exhibited augmented ventilatory responses to both hypoxia and hypercapnia.
      Unexpectedly, RT-PCR analysis has shown the expression of melanocyte-specific
      Mitf mRNA in the brain of bw mice, suggesting the presence of leptomeningeal
      melanocytes. These findings suggest a functional link between skin melanocytes
      and the central respiratory controller that generates respiratory rhythm and
      pattern.

PMID- 17202195
TI  - Visualization of RecA filaments and DNA by fluorescence microscopy.
AB  - We have developed two experimental methods for observing Escherichia coli RecA
      DNA filament under a fluorescence microscope. First, RecA-DNA filaments were
      visualized by immunofluorescence staining with anti-RecA monoclonal antibody.
      Although the detailed filament structures below submicron scale were unable to be
      measured accurately due to optical resolution limit, this method has an advantage
      to analyse a large number of RecA-DNA filaments in a single experiment. Thus, it
      provides a reliable statistical distribution of the filament morphology.
      Moreover, not only RecA filament, but also naked DNA region was visualized
      separately in combination with immunofluorescence staining using anti-DNA
      monoclonal antibody. Second, by using cysteine derivative RecA protein, RecA-DNA
      filament was directly labelled by fluorescent reagent, and was able to observe
      directly under a fluorescence microscope with its enzymatic activity maintained.
      We showed that the RecA-DNA filament disassembled in the direction from 5' to 3'
      of ssDNA as dATP hydrolysis proceeded.

PMID- 17202194
TI  - Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex.
AB  - Members of the family of WASP-family Verprolin homologous proteins (WAVEs)
      activate the Arp2/3 complex to induce actin polymerization. The WAVE family
      comprises three proteins, namely, WAVE1, WAVE2 and WAVE3. Among them, WAVE2 is
      crucial for activation of the Arp2/3 complex for the formation of branched actin
      filaments in lamellipodia. Activation of mitogen-activated protein (MAP) kinase
      signalling results in the phosphorylation of the WAVE family proteins; however,
      which of the three WAVE proteins is phosphorylated is unclear. We found that in
      vitro WAVE2 is directly phosphorylated by a MAP kinase, i.e. extracellular signal
      regulated kinase (ERK) 2. The proline-rich region and the verprolin, cofilin and
      acidic (VCA) region of WAVE2 were phosphorylated. Interestingly, the
      phosphorylated VCA region had a higher affinity for the Arp2/3 complex. However,
      the phosphorylation of the VCA region resulted in reduced induction of Arp2/3
      mediated actin polymerization in vitro. The role of the phosphorylation of the
      proline-rich region was not determined.

PMID- 17202196
TI  - Assessment of condom use among Bolivian truck drivers through the lens of social
      cognitive theory.
AB  - This study demonstrates that Bolivian long distance truck drivers are a high risk
      population of HIV infection and transmission, supporting other global studies
      involving truck drivers and their high risk. The aims of this investigation were
      to estimate the prevalence of high risk behaviors and to identify predictors of
      condom use in this population. Analysis was completed on survey results from 246
      male truckers (aged 18-67). About one in three of the truck drivers (30%)
      reported having had a sexually transmitted infection sometime in their past. More
      than half (56%) reported having sex with casual partners. Other risks involved
      unprotected anal sex. Age and two social cognitive constructs (outcome
      expectations and perceived social norms) predicted condom use from logistic
      regression analysis. The authors discuss the need for expanded HIV/sexually
      transmitted infection prevention programs that incorporate social cognitions.

PMID- 17202197
TI  - Patient dose from 3D rotational neurovascular studies.
AB  - The use of image-guided interventional radiological techniques is increasing in
      prevalence and complexity. Imaging system developments have helped improve the
      information available to interventionalists to plan and guide procedures.
      Information on doses to patients resulting from alternative imaging techniques or
      protocols is useful for both the process of justifying particular procedures and
      in optimizing the resultant exposures. Such information is not always available,
      especially for new or developing imaging techniques. We have undertaken a study
      of doses to patients associated with two alternative imaging methods for pre
      intervention assessment of intracranial aneurysms. In the first technique the
      aneurysm is assessed from a series of digital subtraction angiography (DSA) runs
      taken at different imaging projections. The second technique involved acquiring
      images from one single image run while the imaging system rotated 180 degrees
      around the patient's head. In this technique, the aneurysm was then evaluated
      from a 3D reconstruction of the projection images. Effective doses were
      calculated using a computer model to simulate the exposure geometry and
      parameters. The mean dose from the DSA protocol used at our centre was 3.4 mSv
      and from the 3D rotational angiography (RA) technique was 0.20 mSv.

PMID- 17202198
TI  - Early endothelial and haematological response to cryoplasty compared with balloon
      angioplasty of the superficial femoral artery--a pilot study.
AB  - The purpose of the present study was to assess the course of adhesion molecules
      (intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM),
      e-selectin, p-selectin and monocyte chemoatlractant protein 1 (MCP-1)), growth
      factors (transforming growth factor beta (TGFbeta) and basic fibroblast growth
      factor (bFGF)) and the cytokine tumour necrosis factor alpha (TNFalpha) after
      both angioplasty and cryoplasty. Recently cryoplasty has been suggested as a new
      method to oppose neointimal hyperplasia resulting in restenosis formation. While
      in vitro models have shown that the application of cryothermal energy to the
      endothelium during angioplasty leads to apoptosis induction and reduced
      proliferation rates, no human in vivo proof for an inhibition of neointimal
      hyperplasia exists. For restenosis initiation adhesion molecules, growth factors
      and cytokines play an important role. One possibility to investigate the
      endothelial response to angioplasty is the measurement of the soluble forms of
      adhesion molecules, growth factors and cytokines that are released into the
      circulation after denuding the vessel wall. In the present study we assessed the
      distribution pattern of the soluble forms of e-selectin, p-selectin, ICAM, VCAM,
      MCP-1, TGFbeta, bFGF and TNFalpha after angiography, angioplasty and cryoplasty
      of the femoropopliteal artery in the early course of 4 weeks in 29 patients with
      peripheral arterial occlusive disease. During the 4 weeks after intervention
      levels of e-selectin, ICAM, VCAM and MCP-1 increased after both angioplasty and
      cryoplasty. The course of the screened biomarkers was similar between angioplasty
      and cryoplasty. P-selectin and TGFbeta both decreased after cryoplasty, but not
      significantly. The present results show that the release of adhesion molecules,
      growth factors and cytokines is similar between balloon angioplasty and
      cryoplasty.

PMID- 17202199
TI  - BD ProbeTec ET assay for the diagnosis of gonorrhoea in a high-risk population: a
      protocol for replacing traditional microscopy and culture techniques.
AB  - OBJECTIVES: To evaluate the Neisseria gonorrhoeae Becton Dickinson (BD) ProbeTec
      strand displacement assay (SDA) on female endocervical swab and male first void
      urine against culture for Neisseria gonorrhoeae on female endocervical and
      urethral swab for the diagnosis of N gonorrhoeae infection in genitourinary
      medicine (GUM) attendees. To determine an algorithm for implementation of N
      gonorrhoeae infection screening by SDA in these patients taking account of the
      desirability of having a N gonorrhoeae isolate in people with N gonorrhoeae
      infection. METHODS: Initially, 1582 patients attending the GUM clinic were tested
      for N gonorrhoeae infection by SDA and routine microscopy, and culture. On the
      basis of the results, a protocol for diagnosis of N gonorrhoeae infection by SDA,
      with culture specimens only from patients with a listed risk factor for acquiring
      N gonorrhoeae infection, was devised and implemented. A post implementation audit
      was done to assess the effectiveness of this protocol for routine service use.
      RESULTS: There was good concurrence between the N gonorrhoeae SDA and culture
      results with a N gonorrhoeae infection prevalence rate of 3.4% by both methods.
      All men and 85% of women with N gonorrhoeae infection had an identifiable risk
      factor for acquiring infection. Overall, 38% men and 60% women attending the GUM
      clinic had this listed risk factor for acquiring N gonorrhoeae. Post
      implementation audit confirmed the initial findings. CONCLUSION: Nucleic acid
      amplification techniques like the SDA are sensitive and specific for diagnosis of
      N gonorrhoeae. We were able to list certain risk factors, which were predictive
      of those patients most likely to have N gonorrhoeae infection. To obtain timely
      sensitivity data, a culture specimen should also be submitted at the same time
      from patients deemed to have a listed risk factor for acquiring Neisseria
      gonorrhoeae infection.

PMID- 17202200
TI  - 25-gauge vs 20-gauge system for pars plana vitrectomy: a prospective randomised
      clinical trial.
AB  - AIM: To compare 25-gauge vs 20-gauge system for pars plana vitrectomy in a
      prospective, randomised, controlled clinical trial. METHODS: Three-port pars
      plana vitrectomy was performed in 60 patients belonging to 2 groups. Evaluations
      were performed preoperatively, intraoperatively, during the first three
      postoperative days, at 1 week, and at 1 and 3 months. The main outcome measure
      was time for surgery, divided into duration of wound opening, vitrectomy, retinal
      manipulation and wound closure. RESULTS: The total duration of surgery showed no
      significant difference between the groups (p = 0.67). The 25-gauge group showed
      significantly shorter duration of wound opening (p<0.001) and wound closure
      (p<0.001). In contrast, the vitrectomy duration was significantly longer in the
      25-gauge group (p<0.001). Conjunctival injection and subjective postoperative
      pain showed significantly lower irritation in the 25-gauge group (p<0.001 for
      both). CONCLUSION: The 25-gauge vitrectomy system offered significantly improved
      patient comfort during the first postoperative week. The smaller surgical
      openings facilitated wound healing and minimised pain. Duration of surgery was
      comparable between the two systems-the shorter time needed for wound opening and
      closure in the 25-gauge group being equalised by the longer vitrectomy duration.
      Intraoperative as well as retinal manipulation and illumination caused more
      surgical difficulties using the 25-gauge system.

PMID- 17202201
TI  - The North Jutland County Diabetic Retinopathy Study (NCDRS) 2. Non-ophthalmic
      parameters and clinically significant macular oedema.
AB  - BACKGROUND: The influence of non-ophthalmic parameters on the prevalence of
      clinically significant macular oedema has not been unambiguously established. The
      present study was initiated with the aim of clarification. METHODS: This cross
      sectional study comprised 656 type 1 and 328 type 2 diabetic subjects undergoing
      retinopathy screening in the county of North Jutland. The association between the
      presence of clinically significant macular oedema and blood pressure, HbA1c, BMI,
      age, onset of diabetes, duration of diabetes, blood-pressure-reducing medication,
      lipid-lowering medication, neuropathy and urinary albumin excretion was explored
      using multiple logistic regression analysis. RESULTS: We found no significant
      association between the presence of clinically significant macular oedema and any
      of the examined parameters in type 1 diabetic subjects. In type 2 diabetic
      subjects, the duration of diabetes, HbA1c, neuropathy and increased urinary
      albumin excretion was significantly associated with the presence of clinically
      significant macular oedema. CONCLUSIONS: The risk factors for clinically
      significant macular oedema differ in type 1 and type 2 diabetic subjects and can
      account only in part for this manifestation.

PMID- 17202203
TI  - Long-term results of sealed capsule irrigation using distilled water to prevent
      posterior capsule opacification: a prospective clinical randomised trial.
AB  - BACKGROUND: We investigated long-term safety and efficacy of sealed capsule
      irrigation (SCI) during cataract surgery to prevent posterior capsule
      opacification (PCO). METHODS: One eye of each of 17 patients (mean age: 70.1+/
      9.7 years) who presented with bilateral cataracts was randomly chosen for SCI
      treatment. After phacoemulsification, the capsular bag was vacuum sealed with the
      PerfectCapsule device (Milvella) followed by SCI using distilled water for two
      minutes. No vacuum loss occurred during irrigation. Each patient's fellow eye
      served as a control. One hydrophilic acrylic intraocular lens model was implanted
      in all eyes. Five patients had to be excluded due to deep anterior chamber, small
      pupil or unilateral surgery. Follow-up examinations took place one day and one,
      three, six, 12 and 24 months after surgery. We evaluated safety parameters,
      anterior capsule (AC) overlapping and PCO. RESULTS: Postoperatively, mean best
      corrected visual acuity, pachymetry, endothelial cell count, intraocular
      pressure, AC overlapping and PCO showed no statistically significant difference
      between SCI and the control group (p>0.05, Wilcoxon test). CONCLUSION: SCI is a
      safe procedure and enables the specific pharmacological targeting of lens
      epithelial cells inside the capsular bag. Using distilled water, however, it is
      not possible to reduce PCO development significantly. Thus, alternative
      substances should be evaluated.

PMID- 17202204
TI  - Refractive errors in neurofibromatosis type 1 and type 2.
AB  - OBJECTIVE: To document the prevalence of refractive errors in patients with
      neurofibromatosis type 1 (NF1) and type 2 (NF2) and to compare it with that of
      age- and sex-matched controls. METHODS: 82 patients with NF1, 21 patients with
      NF2 and 103 age- and sex-matched controls were evaluated in this prospective
      observational case-control study. Cycloplegic autorefraction and dilated fundus
      examination were performed. Myopia was defined as the spherical equivalent
      refraction of at least -0.50 diopters (D), hyperopia as the spherical equivalent
      refraction of at least 2.0 D and astigmatism as the cylinder of at least 1.0 D.
      Main outcome measures were refractive error, IQ, years of education, height,
      weight and body mass index (BMI). RESULTS: The prevalence of myopia was 23.1% in
      patients with NF1, 23.8% in patients with NF2 and 16.5% in age- and sex-matched
      controls. These differences were significant (p<0.03, p<0.03), and adjusting for
      intelligence, education, height, weight and BMI increased the significance of
      this finding (p<0.001, p<0.001). The prevalences of astigmatism and hyperopia
      were similar in both groups. CONCLUSION: A high prevalence of myopia seems to be
      an additional feature of NF1 and NF2.

PMID- 17202205
TI  - Photodynamic treatment versus photodynamic treatment associated with systemic
      steroids for idiopathic choroidal neovascularisation.
AB  - AIM: To compare photodynamic therapy (PDT) with PDT associated with systemic
      steroids (SS) for the control of juxta/subfoveal idiopathic choroidal
      neovascularisation (ICNV). METHODS: Patients with juxta/subfoveal ICNV were
      randomised and then treated. Visual gain and loss were defined as improvement in
      or worsening for two or more lines of best-corrected visual acuity (BCVA),
      respectively. Choroidal neovascularisation size after treatment was classified as
      "increased" and "reduced" if it was increased or reduced by >200 microm(2),
      respectively. RESULTS: 10 patients were treated with PDT, 10 with SS followed by
      PDT. The median follow-up time was 22 and 21 months for the "steroid+PDT group"
      and the "PDT group", respectively. At 1 year, in the PDT group, five patients had
      stable/improved BCVA, and five became worse; the mean number of PDT was 2.3; in
      the steroid+PDT group, all patients were stable/improved and the mean number of
      PDT was 1.2. The difference between the two groups was significant (p<0.05). At 1
      year, the ICNV size after treatment was better in the steroid+PDT group than in
      the PDT group (p<0.05). CONCLUSION: The use of SS before PDT has shown better
      BCVA outcome than PDT alone (p<0.05), reducing the mean number of PDT
      applications (1.2 vs 2.3, respectively), with smaller scar size.

PMID- 17202206
TI  - High-frequency epigenetic repression and silencing of retroviruses can be
      antagonized by histone deacetylase inhibitors and transcriptional activators, but
      uniform reactivation in cell clones is restricted by additional mechanisms.
AB  - Integrated retroviral DNA is subject to epigenetic gene silencing, but the viral
      and host cell properties that influence initiation, maintenance, and reactivation
      are not fully understood. Here we describe rapid and high-frequency epigenetic
      repression and silencing of integrated avian sarcoma virus (ASV)-based vector
      DNAs in human HeLa cells. Initial studies utilized a vector carrying the strong
      human cytomegalovirus (hCMV) immediate-early (IE) promoter to drive expression of
      a green fluorescent protein (GFP) reporter gene, and cells were sorted into two
      populations based on GFP expression [GFP(+) and GFP(-)]. Two potent epigenetic
      effects were observed: (i) a very broad distribution of GFP intensities among
      cells in the GFP(+) population as well as individual GFP(+) clones and (ii) high
      frequency GFP reporter gene silencing in GFP(-) cells. We previously showed that
      histone deacetylases (HDACs) can associate with ASV DNA soon after infection and
      may act to repress viral transcription at the level of chromatin. Consistent with
      this finding, we report here that treatment with the histone deacetylase
      inhibitor trichostatin A (TSA) induces GFP activation in GFP(-) cells and can
      also increase GFP expression in GFP(+) cells. In the case of the GFP(-)
      populations, we found that after removal of TSA, GFP silencing was reestablished
      in a subset of cells. We used that finding to enrich for stable GFP(-) cell
      populations in which viral GFP reporter expression could be reactivated by TSA;
      furthermore, we found that the ability to isolate such populations was
      independent of the promoter driving the GFP gene. In such enriched cultures, hCMV
      IE-driven, but not the viral long terminal repeat-driven, silent GFP reporter
      expression could be reactivated by the transcriptional activator prostratin.
      Microscopy-based studies using synchronized cells revealed variegated
      reactivation in cell clones, indicating that secondary epigenetic effects can
      restrict reactivation from silencing. Furthermore we found that entry into S
      phase was not required for reactivation. We conclude that HDACs can act rapidly
      to initiate and maintain promoter-independent retroviral epigenetic repression
      and silencing but that reactivation can be restricted by additional mechanisms.

PMID- 17202207
TI  - Efficient DNA packaging of bacteriophage PRD1 requires the unique vertex protein
      P6.
AB  - The assembly of bacteriophage PRD1 proceeds via formation of empty procapsids
      containing an internal lipid membrane, into which the linear double-stranded DNA
      genome is subsequently packaged. The packaging ATPase P9 and other putative
      packaging proteins have been shown to be located at a unique vertex of the PRD1
      capsid. Here, we describe the isolation and characterization of a suppressor
      sensitive PRD1 mutant deficient in the unique vertex protein P6. Protein P6 was
      found to be an essential part of the PRD1 packaging machinery; its absence leads
      to greatly reduced packaging efficiency. Lack of P6 was not found to affect
      particle assembly, because in the P6-deficient mutant infection, wild-type (wt)
      amounts of particles were produced, although most were empty. P6 was determined
      not to be a specificity factor, as the few filled particles seen in the P6
      deficient infection contained only PRD1-specific DNA. The presence of P6 was not
      necessary for retention of DNA in the capsid once packaging had occurred, and P6
      deficient DNA-containing particles were found to be stable and infectious, albeit
      not as infectious as wt PRD1 virions. A packaging model for bacteriophage PRD1,
      based on previous results and those obtained in this study, is presented.

PMID- 17202208
TI  - Novel beta-barrel fold in the nuclear magnetic resonance structure of the
      replicase nonstructural protein 1 from the severe acute respiratory syndrome
      coronavirus.
AB  - The nonstructural protein 1 (nsp1) of the severe acute respiratory syndrome
      coronavirus has 179 residues and is the N-terminal cleavage product of the viral
      replicase polyprotein that mediates RNA replication and processing. The specific
      function of nsp1 is not known. Here we report the nuclear magnetic resonance
      structure of the nsp1 segment from residue 13 to 128, which represents a novel
      alpha/beta-fold formed by a mixed parallel/antiparallel six-stranded beta-barrel,
      an alpha-helix covering one opening of the barrel, and a 3(10)-helix alongside
      the barrel. We further characterized the full-length 179-residue protein and show
      that the polypeptide segments of residues 1 to 12 and 129 to 179 are flexibly
      disordered. The structure is analyzed in a search for possible correlations with
      the recently reported activity of nsp1 in the degradation of mRNA.

PMID- 17202209
TI  - Human cytomegalovirus UL38 protein blocks apoptosis.
AB  - Apoptosis is an innate cellular defense response to viral infection. The slow
      replicating human cytomegalovirus (HCMV) blocks premature death of host cells
      prior to completion of the infection cycle. In this study, we report that the
      HCMV UL38 gene encodes a cell death inhibitory protein. A mutant virus lacking
      the pUL38 coding sequence, ADdlUL38, grew poorly in human fibroblasts, failed to
      accumulate viral DNA to wild-type levels, and induced excessive death of infected
      cells. Cells expressing pUL38 were resistant to cell death upon infection and
      effectively supported the growth of ADdlUL38. Cells infected with the pUL38
      deficient virus showed morphological changes characteristic of apoptosis,
      including cell shrinkage, membrane blebbing, vesicle release, and chromatin
      condensation and fragmentation. The proteolytic cleavage of two key enzymes
      involved in apoptosis, namely, caspase 3 and poly(ADP-ribose) polymerase, was
      activated upon ADdlUL38 infection, and the cleavage was blocked in cells
      expressing pUL38. The pan-caspase inhibitor Z-VAD-FMK largely restored the growth
      of ADdlUL38 in normal fibroblasts, indicating that the defective growth of the
      mutant virus mainly resulted from premature death of host cells. Furthermore,
      cells expressing pUL38 were resistant to cell death induced by a mutant
      adenovirus lacking the antiapoptotic E1B-19K protein or by thapsigargin, which
      disrupts calcium homeostasis in the endoplasmic reticulum. Taken together, these
      results indicate that the HCMV protein pUL38 suppresses apoptosis, blocking
      premature death of host cells to facilitate efficient virus replication.

PMID- 17202211
TI  - Cytotoxic T-lymphocyte responses to human papillomavirus type 16 E5 and E7
      proteins and HLA-A*0201-restricted T-cell peptides in cervical cancer patients.
AB  - Previously, we found that human papillomavirus type 16 (HPV-16) E5 protein is a
      tumor rejection antigen and can induce cytotoxic T-lymphocyte (CTL) activity.
      Therefore, in this study, human leukocyte antigen A*0201 (HLA-A*0201)-restricted
      human CTL epitopes of HPV-16 E5 protein were identified using a bioinformatics
      approach, and the abilities of these predicted peptides to induce an immune
      response in HLA-A*0201 transgenic mice were confirmed by assaying E5-specific
      CTLs and in vitro-generated CTLs from normal peripheral blood T lymphocytes of
      HLA-A2-positive human donors. Second, the CTL responses to HLA-A*0201 CTL
      epitopes (E5 63-71 and E7 11-20) were examined in HPV-16-infected patients with
      HLA-A2. Third, the effect of HLA-A-type alleles on CTL activities in response to
      the entire E5 and E7 proteins was examined in cervical cancer patients. E5 and E7
      peptides (but not the whole proteins) stimulated E5- and E7-specific CTL recall
      responses in HPV-16- and HLA-A2-positive cervical cancer patients, and HPV-16 E5
      and E7 proteins stimulated naive T cells in HPV-16-negative cervical cancer
      patients with HLA-A11 and -A24 haplotypes. In summary, this is the first
      demonstration that E5 63-71 is an HLA-A*0201-restricted T-cell epitope of HPV-16
      E5.

PMID- 17202210
TI  - A structured viroid RNA serves as a substrate for dicer-like cleavage to produce
      biologically active small RNAs but is resistant to RNA-induced silencing complex
      mediated degradation.
AB  - RNA silencing is a potent means of antiviral defense in plants and animals. A
      hallmark of this defense response is the production of 21- to 24-nucleotide viral
      small RNAs via mechanisms that remain to be fully understood. Many viruses encode
      suppressors of RNA silencing, and some viral RNAs function directly as silencing
      suppressors as counterdefense. The occurrence of viroid-specific small RNAs in
      infected plants suggests that viroids can trigger RNA silencing in a host,
      raising the question of how these noncoding and unencapsidated RNAs survive
      cellular RNA-silencing systems. We address this question by characterizing the
      production of small RNAs of Potato spindle tuber viroid (srPSTVds) and
      investigating how PSTVd responds to RNA silencing. Our molecular and biochemical
      studies provide evidence that srPSTVds were derived mostly from the secondary
      structure of viroid RNAs. Replication of PSTVd was resistant to RNA silencing,
      although the srPSTVds were biologically active in guiding RNA-induced silencing
      complex (RISC)-mediated cleavage, as shown with a sensor system. Further analyses
      showed that without possessing or triggering silencing suppressor activities, the
      PSTVd secondary structure played a critical role in resistance to RISC-mediated
      cleavage. These findings support the hypothesis that some infectious RNAs may
      have evolved specific secondary structures as an effective means to evade RNA
      silencing in addition to encoding silencing suppressor activities. Our results
      should have important implications in further studies on RNA-based mechanisms of
      host-pathogen interactions and the biological constraints that shape the
      evolution of infectious RNA structures.

PMID- 17202212
TI  - Natural antibody and complement mediate neutralization of influenza virus in the
      absence of prior immunity.
AB  - Early control of virus replication by the innate immune response is essential to
      allow time for the generation of a more effective adaptive immune response. As an
      important component of innate immunity, complement has been shown to be necessary
      for protection against numerous microbial infections. This study was undertaken
      to investigate the role of complement in neutralizing influenza virus. Results
      demonstrated that the classical pathway of complement mediated serum
      neutralization of influenza virus. Although nonimmune serum neutralized influenza
      virus, the mechanism of virus neutralization (VN) required antibody, as sera from
      RAG1-deficient mice lacked VN activity; moreover, purified natural immunoglobulin
      M (IgM) restored VN activity to antibody-deficient sera. The mechanism of VN by
      natural IgM and complement was associated with virion aggregation and coating of
      the viral hemagglutinin receptor; however, viral lysis did not significantly
      contribute to VN. Additionally, reconstitution of RAG1-deficient mice with
      natural IgM resulted in delayed morbidity during influenza virus infection.
      Collectively, these results provide evidence that natural IgM and the early
      components of the classical pathway of complement work in concert to neutralize
      influenza virus and that this interaction may have a significant impact on the
      course of influenza viral pneumonia.

PMID- 17202213
TI  - Enzymatic defects of the nsP2 proteins of Semliki Forest virus temperature
      sensitive mutants.
AB  - We have analyzed the biochemical consequences of mutations that affect viral RNA
      synthesis in Semliki Forest virus temperature-sensitive (ts) mutants. Of the six
      mutations mapping in the multifunctional replicase protein nsP2, three were
      located in the N-terminal helicase region and three were in the C-terminal
      protease domain. Wild-type and mutant nsP2s were expressed, purified, and assayed
      for nucleotide triphosphatase (NTPase), RNA triphosphatase (RTPase), and protease
      activities in vitro at 24 degrees C and 35 degrees C. The protease domain mutants
      (ts4, ts6, and ts11) had reduced protease activity at 35 degrees C but displayed
      normal NTPase and RTPase. The helicase domain mutation ts1 did not have enzymatic
      consequences, whereas ts13a and ts9 reduced both NTPase and protease activities
      but in different and mutant-specific ways. The effects of these helicase domain
      mutants on protease function suggest interdomain interactions within nsP2. NTPase
      activity was not directly required for protease activity. The similarities of the
      NTPase and RTPase results, as well as competition experiments, suggest that these
      two reactions utilize the same active site. The mutations were also studied in
      recombinant viruses first cultivated at the permissive temperature and then
      shifted up to the restrictive temperature. Processing of the nonstructural
      polyprotein was generally retarded in cells infected with viruses carrying the
      ts4, ts6, ts11, and ts13a mutations, and a specific defect appeared in ts9. All
      mutations except ts13a were associated with a large reduction in the production
      of the subgenomic 26S mRNA, indicating that both protease and helicase domains
      influence the recognition of the subgenomic promoter during virus replication.

PMID- 17202214
TI  - Theory of lethal mutagenesis for viruses.
AB  - Mutation is the basis of adaptation. Yet, most mutations are detrimental, and
      elevating mutation rates will impair a population's fitness in the short term.
      The latter realization has led to the concept of lethal mutagenesis for curing
      viral infections, and work with drugs such as ribavirin has supported this
      perspective. As yet, there is no formal theory of lethal mutagenesis, although
      reference is commonly made to Eigen's error catastrophe theory. Here, we propose
      a theory of lethal mutagenesis. With an obvious parallel to the epidemiological
      threshold for eradication of a disease, a sufficient condition for lethal
      mutagenesis is that each viral genotype produces, on average, less than one
      progeny virus that goes on to infect a new cell. The extinction threshold
      involves an evolutionary component based on the mutation rate, but it also
      includes an ecological component, so the threshold cannot be calculated from the
      mutation rate alone. The genetic evolution of a large population undergoing
      mutagenesis is independent of whether the population is declining or stable, so
      there is no runaway accumulation of mutations or genetic signature for lethal
      mutagenesis that distinguishes it from a level of mutagenesis under which the
      population is maintained. To detect lethal mutagenesis, accurate measurements of
      the genome-wide mutation rate and the number of progeny per infected cell that go
      on to infect new cells are needed. We discuss three methods for estimating the
      former. Estimating the latter is more challenging, but broad limits to this
      estimate may be feasible.

PMID- 17202215
TI  - Understanding the failure of CD8+ T-cell vaccination against simian/human
      immunodeficiency virus.
AB  - Although CD8+ T cells play an important role in controlling viral infections,
      boosting specific CD8+ T cells by prophylactic vaccination with simian
      immunodeficiency virus (SIV) epitopes fails to provide sterilizing immunity.
      Viral replication rates and viral contraction rates after the peak viremia hardly
      depend on the presence of memory CD8+ T cells. To study these paradoxical
      findings, we parameterize novel mathematical models for acute SIV and human
      immunodeficiency virus infection. These models explain that failure of
      vaccination is due to the fact that effector/target ratios are too low during the
      viral expansion phase. Because CD8+ T cells require cell-to-cell contacts, immune
      protection requires high effector/target ratios at the primary site of infection.
      Effector/target ratios become favorable for immune control at the time of the
      peak in the viral load when the virus becomes limited by other factors, such as
      the availability of uninfected target cells. At the viral set point,
      effector/target ratios are much higher, and perturbations of the number of CD8+
      effector cells have a large impact on the viral load. Such protective
      effector/target ratios are difficult to achieve with nucleic acid- or protein
      based vaccines.

PMID- 17202216
TI  - Initiation at the third in-frame AUG codon of open reading frame 3 of the
      hepatitis E virus is essential for viral infectivity in vivo.
AB  - To determine the initiation strategy of the hepatitis E virus (HEV) open reading
      frame 3 (ORF3), we constructed five HEV mutants with desired mutations in the
      ORF1 and ORF2 junction region and tested their levels of in vivo infectivity in
      pigs. A mutant with a C-terminally truncated ORF3 is noninfectious in pigs,
      indicating that an intact ORF3 is required for in vivo infectivity. Mutations
      with substitutions in the first in-frame AUG in the junction region or with the
      same T insertion at the corresponding position of HEV genotype 4 did not affect
      the virus infectivity or rescue, although mutations with combinations of the two
      affected virus recovery efficiency, and a single mutation at the third in-frame
      AUG completely abolished virus infectivity in vivo, indicating that the third in
      frame AUG in the junction region is required for virus infection and is likely
      the authentic initiation site for ORF3. A conserved double stem-loop RNA
      structure, which may be important for HEV replication, was identified in the
      junction region. This represents the first report of using a unique homologous
      pig model system to study the molecular mechanism of HEV replication and to
      systematically and definitively identify the authentic ORF3 initiation site.

PMID- 17202217
TI  - The level of viral antigen presented by hepatocytes influences CD8 T-cell
      function.
AB  - CD8 T cells exert their antiviral function through cytokines and lysis of
      infected cells. Because hepatocytes are susceptible to noncytolytic mechanisms of
      viral clearance, CD8 T-cell antiviral efficiency against hepatotropic viruses has
      been linked to their capacity to produce gamma interferon (IFN-gamma) and tumor
      necrosis factor alpha (TNF-alpha). On the other hand, intrahepatic cytokine
      production triggers the recruitment of mononuclear cells, which sustain acute and
      chronic liver damage. Using virus-specific CD8 T cells and human hepatocytes, we
      analyzed the modulation of virus-specific CD8 T-cell function after recognition
      peptide-pulsed or virally infected hepatocytes. We observed that hepatocyte
      antigen presentation was generally inefficient, and the quantity of viral antigen
      strongly influenced CD8 T-cell antiviral function. High levels of hepatitis B
      virus production induced robust IFN-gamma and TNF-alpha production in virus
      specific CD8 T cells, while limiting amounts of viral antigen, both in hepatocyte
      like cells and naturally infected human hepatocytes, preferentially stimulated
      CD8 T-cell degranulation. Our data document a mechanism where virus-specific CD8
      T-cell function is influenced by the quantity of virus produced within
      hepatocytes.

PMID- 17202218
TI  - Upstream AP1- and CREB-binding sites confer high basal activity on the adeno
      associated virus type 5 capsid gene promoter.
AB  - In contrast to the prototype adeno-associated virus type 2 (AAV2), the capsid
      gene P41 promoter of AAV5, within viral constructs that lack inverted terminal
      repeat sequences, displays a high basal level of expression in 293 cells in the
      absence of coinfecting adenovirus. Here we demonstrate that this was due to
      differences in the relative strengths of the core promoter elements and to the
      presence of active binding sites for the transcription factors CREB and AP1
      within the upstream region of P41 that are absent from the AAV2 capsid gene
      promoter P40. These differences also governed the relative basal activity of the
      AAV capsid gene promoters within near-full-length viral genomes.

PMID- 17202219
TI  - Dual selection pressure by drugs and HLA class I-restricted immune responses on
      human immunodeficiency virus type 1 protease.
AB  - To determine the influence of human immunodeficiency virus type 1 (HIV-1)
      specific CD8+ T cells on the development of drug resistance mutations in the HIV
      1 protease, we analyzed protease sequences from viruses from a human leukocyte
      antigen class I (HLA class I)-typed cohort of 94 HIV-1-positive individuals. In
      univariate statistical analyses (Fisher's exact test), minor and major drug
      resistance mutations as well as drug-associated polymorphisms showed associations
      with HLA class I alleles. All correlations with P values of 0.05 or less were
      considered to be relevant without corrections for multiple tests. A subset of
      these observed correlations was experimentally validated by enzyme-linked
      immunospot assays, allowing the definition of 10 new epitopes recognized by CD8+
      T cells from patients with the appropriate HLA class I type. Several drug
      resistance-associated mutations in the protease acted as escape mutations;
      however, cells from many patients were still able to generate CD8+ T cells
      targeting the escape mutants. This result presumably indicates the usage of
      different T-cell receptors by CD8+ T cells targeting these epitopes in these
      patients. Our results support a fundamental role for HLA class I-restricted
      immune responses in shaping the sequence of the HIV-1 protease in vivo. This role
      may have important clinical implications both for the understanding of drug
      resistance pathways and for the design of therapeutic vaccines targeting drug
      resistant HIV-1.

PMID- 17202220
TI  - Andes and Prospect Hill hantaviruses differ in early induction of interferon
      although both can downregulate interferon signaling.
AB  - Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease which is
      thought to result from a dysregulated immune response to infection with
      pathogenic hantaviruses, such as Sin Nombre virus or Andes virus (ANDV). Other
      New World hantaviruses, such as Prospect Hill virus (PHV), have not been
      associated with human disease. Activation of an antiviral state and cell
      signaling in response to hantavirus infection were examined using human primary
      lung endothelial cells, the main target cell infected in HPS patients. PHV, but
      not ANDV, was found to induce a robust beta interferon (IFN-beta) response early
      after infection of primary lung endothelial cells. The level of IFN induction
      correlated with IFN regulatory factor 3 (IRF-3) activation, in that IRF-3
      dimerization and nuclear translocation were detected in PHV but not ANDV
      infection. In addition, phosphorylated Stat-1/2 levels were significantly lower
      in the ANDV-infected cells relative to PHV. Presumably, this reflects the lower
      level of IRF-3 activation and initial IFN induced by ANDV relative to PHV. To
      determine whether, in addition, ANDV interference with IFN signaling also
      contributed to the low Stat-1/2 activation seen in ANDV infection, the levels of
      exogenous IFN-beta-induced Stat-1/2 activation detectable in uninfected versus
      ANDV- or PHV-infected Vero-E6 cells were examined. Surprisingly, both viruses
      were found to downregulate IFN-induced Stat-1/2 activation. Analysis of cells
      transiently expressing only ANDV or PHV glycoproteins implicated these proteins
      in this downregulation. In conclusion, while both viruses can interfere with IFN
      signaling, there is a major difference in the initial interferon induction via
      IRF-3 activation between ANDV and PHV in infected primary endothelial cells, and
      this correlates with the reported differences in pathogenicity of these viruses.

PMID- 17202221
TI  - ATP-dependent minor groove recognition of TA base pairs is required for template
      melting by the E1 initiator protein.
AB  - Template melting is an essential step in the initiation of DNA replication, but
      the mechanism of template melting is unknown for any replicon. Here we
      demonstrate that melting of the bovine papillomavirus type 1 ori is a sequence
      dependent process which relies on specific recognition of TA base pairs in the
      minor groove by the E1 initiator. We show that correct template melting is a
      prerequisite for the formation of a stable double hexamer with helicase activity
      and that ori mutants that fail to melt correctly are defective for ori unwinding
      and DNA replication in vivo. Our results also indicate that melting of the DNA is
      achieved by destabilization of the double helix along its length through multiple
      interactions with E1, each of which is responsible for melting of a few base
      pairs, resulting in the extensive melting that is required for initiation of DNA
      replication.

PMID- 17202222
TI  - The IE2 60-kilodalton and 40-kilodalton proteins are dispensable for human
      cytomegalovirus replication but are required for efficient delayed early and late
      gene expression and production of infectious virus.
AB  - The human cytomegalovirus (HCMV) IE2 86-kDa protein is an essential
      transactivator of viral and cellular gene expression. Additional proteins of 60
      and 40 kDa are expressed from the IE2 gene at late times postinfection and are
      identical to the C terminus of IE2 86. We have constructed HCMV recombinants that
      express wild-type full-length IE2 86 but do not express the IE2 40- and 60-kDa
      proteins. Each of these recombinants is viable, indicating that neither the 60
      kDa nor the 40-kDa protein is required for virus replication, either alone or in
      combination. Cells infected with the IE2 60 and IE2 40 deletion mutants, however,
      exhibit decreased expression of selected viral genes at late times. In
      particular, expression of the viral DNA replication factor UL84 is affected by
      the deletion of IE2 40, and expression of the tegument protein pp65 (ppUL83) is
      affected by the deletion of both IE2 40 and IE2 60. IE2 60 and IE2 40 are also
      required for the production of normal levels of infectious virus. Finally, IE2 40
      appears to function as a repressor of major immediate-early transcription in the
      infected cell. These results begin to define functions for the IE2 60- and IE2 40
      kDa proteins and indicate that these products contribute both to the expression
      of selected viral genes and to the overall progression of the infection.

PMID- 17202223
TI  - Characterization of the nuclear export signal in the coronavirus infectious
      bronchitis virus nucleocapsid protein.
AB  - The nucleocapsid (N) protein of infectious bronchitis virus (IBV) localizes to
      the cytoplasm and nucleolus and contains an eight-amino-acid nucleolar retention
      motif. In this study, a leucine-rich nuclear export signal (NES) (291-LQLDGLHL
      298) present in the C-terminal region of the IBV N protein was analyzed by using
      alanine substitution and deletion mutagenesis to investigate the relative
      contributions that leucine residues make to nuclear export and where these
      residues are located on the structure of the IBV N protein. The analysis
      indicated that Leu296 and Leu298 are required for efficient nuclear export of the
      protein. Structural information indicated that both of these amino acids are
      available for interaction with protein complexes involved in this process.
      However, export of N protein from the nucleus/nucleolus was not inhibited by
      leptomycin B treatment, indicating that N protein nuclear export is independent
      of the CRM1-mediated export pathway.

PMID- 17202224
TI  - Evolution of CXCR4-using human immunodeficiency virus type 1 SF162 is associated
      with two unique envelope mutations.
AB  - CCR5-using human immunodeficiency virus type 1 (HIV-1) isolates typically gain
      CXCR4 use via multiple mutations in V3 and often V1/V2 regions of envelope, and
      patterns of mutations are distinct for each isolate. Here, we report that
      multiple CXCR4-using variants of a parental CCR5-using HIV-1 isolate, SF162,
      obtained by either target cell selection or CCR5 inhibition have a common
      mutation pattern characterized by the same two V3 mutations and that these
      mutations preexisted in some of the SF162 stocks. These results imply that SF162
      has a single pathway for acquiring CXCR4 use and that prolonged culture is
      sufficient to select for R5X4 variants.

PMID- 17202225
TI  - Transforming growth factor beta enhances respiratory syncytial virus replication
      and tumor necrosis factor alpha induction in human epithelial cells.
AB  - Asthma is characterized as a chronic inflammatory disease associated with
      significant tissue remodeling. Patients with asthma are more susceptible to virus
      induced exacerbation, which subsequently can lead to increased rates of
      hospitalization and mortality. While the most common cause of asthma-related
      deaths is respiratory viral infections, the underlying factors in the lung
      environment which render asthmatic subjects more susceptible to viral
      exacerbation are not yet identified. Since transforming growth factor beta (TGF
      beta) is a critical cytokine for lung tissue remodeling and asthma phenotype, we
      have focused on the effects of TGF-beta on viral replication and virus-induced
      inflammation. Treatment of human epithelial cells with TGF-beta increased
      respiratory syncytial virus (RSV) replication by approximately fourfold. Tumor
      necrosis factor alpha (TNF-alpha) mRNA and protein expression were also
      significantly increased above levels with RSV infection alone. The increase in
      RSV replication and TNF-alpha expression after TGF-beta treatment was concomitant
      with an increase in virus-induced p38 mitogen-activated protein kinase
      activation. Our data reveal a novel effect for TGF-beta on RSV replication and
      provide a potential mechanism for the exaggerated inflammatory response observed
      in asthmatic subjects during respiratory viral infections.

PMID- 17202226
TI  - Subcellular location of serum- and glucocorticoid-induced kinase-1 in renal and
      mammary epithelial cells.
AB  - Serum- and glucocorticoid-induced kinase-1 (SGK1) is involved in aldosterone
      induced Na(+) reabsorption by increasing epithelial Na(+) channel (ENaC) activity
      in cortical collecting duct (CCD) cells, but its exact mechanisms of action are
      unknown. Although several potential targets such as Nedd4-2 have been described
      in expression systems, endogenous substrates mediating SGK1's physiological
      effects remain to be identified. In addition, subcellular localization studies of
      SGK1 have provided controversial results. We determined the subcellular location
      of SGK1 using SGK1-autofluorescent protein (AFP) fusion proteins. Rabbit CCD
      (RCCT-28A) cells were transiently transfected with a construct encoding for SGK1
      AFP and were stained or cotransfected with markers for various subcellular
      compartments. In live cells, transiently expressed SGK1-AFP clearly colocalized
      with the mitochondrial marker rhodamine 123. Similarly, SGK1-AFP colocalized with
      the mitochondrial marker MitoTracker when stably expressed using a retroviral
      system in either RCCT-28A cells or the mammary epithelial cell line MCF10A. To
      determine which region of SGK1 is responsible for this subcellular localization,
      we generated RCCT-28A cell lines stably expressing SGK1 mutants. The results
      indicate that the NH(2)-terminal 60-amino acid region of SGK1 is necessary and
      sufficient for its subcellular localization. Localization of SGK1 to the
      mitochondria raises the possibility that SGK1 may play a role in regulating
      energy metabolism.

PMID- 17202227
TI  - The actin cytoskeleton regulates exocytosis of all neutrophil granule subsets.
AB  - A comprehensive analysis of the role of the actin cytoskeleton in exocytosis of
      the four different neutrophil granule subsets had not been performed previously.
      Immunoblot analysis showed that, compared with plasma membrane, there was less
      actin associated with secretory vesicles (SV, 75%), gelatinase granules (GG,
      40%), specific granules (SG, 10%), and azurophil granules (AG, 5%). Exocytosis of
      SV, SG, and AG was measured as increased plasma membrane expression of CD35,
      CD66b, and CD63, respectively, with flow cytometry, and GG exocytosis was
      measured as gelatinase release with an ELISA. N-formylmethionyl-leucyl
      phenylalanine (FMLP) stimulated exocytosis of SV, GG, and SG with an ED(50) of
      15, 31, and 28 nM, respectively, with maximal response at 10(-7) M FMLP by 5 min,
      while no exocytosis of AG was detected. Disruption of the actin cytoskeleton by
      latrunculin A and cytochalasin D induced a decrease in FMLP-stimulated CD35
      expression after an initial increase. Both drugs enhanced the rate and extent of
      FMLP-stimulated GG, SG, and AG exocytosis, while the EC(50) for FMLP was not
      altered. We conclude that the actin cytoskeleton controls access of neutrophil
      granules to the plasma membrane, thereby limiting the rate and extent of
      exocytosis of all granule subsets. Differential association of actin with the
      four granule subsets was not associated with graded exocytosis.

PMID- 17202228
TI  - Co-occurrence of affective and schizophrenia spectrum disorders with PINK1
      mutations.
AB  - OBJECTIVE: To investigate a possible association of mutations in the PTEN-induced
      putative kinase 1 (PINK1) gene with psychiatric disorders in a large family with
      monogenic parkinsonism. METHOD: 20 members of a family (4 homozygous, 11
      heterozygous and 5 non-mutation carriers) were investigated for the presence of
      psychiatric disorders using the structured clinical interview for Diagnostic and
      Statistical Manual of Mental Disorders, 4th edition (DSM-IV); information on
      three additional heterozygous mutation carriers was obtained according to the
      family history research diagnostic criteria. RESULTS: We found predominantly
      affective and schizophrenia spectrum disorders in 11 (61%) of the 18 mutation
      carriers and in 1 (20%) of the 5 mutation-negative cases. CONCLUSIONS: First,
      affective and psychotic symptoms may be part of the phenotypic spectrum or even
      the sole manifestation of PINK1 mutations. Second, patients with familial
      movement disorders associated with psychiatric conditions may serve as a valuable
      study population to explore (genetic) causes of neuropsychiatric disease.

PMID- 17202229
TI  - Evidence that congenital hydrocephalus is a precursor to idiopathic normal
      pressure hydrocephalus in only a subset of patients.
AB  - OBJECTIVE: To identify the proportion of patients in a large idiopathic normal
      pressure hydrocephalus (INPH) cohort with large head circumference (HC) who
      presumably have congenital hydrocephalus that has not become clinically apparent
      until late in life. METHODS: HC was measured in 158 patients diagnosed with
      communicating INPH and assigned to HC centile range adjusted for height and sex.
      The proportion of patients with INPH and HC above the 97th, 90th or 50th centiles
      was compared with the proportion expected in a normal population. RESULTS: The
      proportion of patients with HC >90th centile was significantly larger than would
      be expected in a normal distribution (19.6% vs 10%, p = 0.0001), as was the
      proportion of patients with HC >97th centile (8.9% vs 3%, p = 0.0001). The
      relative association between INPH and HC >97th centile was nearly tripled
      (relative association 2.95; CI 1.36 to 6.41), but the relative association
      between INPH and HC >50th centile was not significantly higher than predicted
      (relative association 1.13; CI 0.95 to 1.34). CONCLUSION: A significantly larger
      proportion of elderly adults with INPH have a HC greater than the 90th or 97th
      centile than predicted by population norms, supporting the concept that
      compensated congenital hydrocephalus that does not become symptomatic until late
      in life is one aetiology of INPH, but is not responsible for all INPH. The
      mechanism that leads to the development of INPH in most patients remains elusive.

PMID- 17202230
TI  - Calibration of visually guided reaching is driven by error-corrective learning
      and internal dynamics.
AB  - The sensorimotor calibration of visually guided reaching changes on a trial-to
      trial basis in response to random shifts in the visual feedback of the hand. We
      show that a simple linear dynamical system is sufficient to model the dynamics of
      this adaptive process. In this model, an internal variable represents the current
      state of sensorimotor calibration. Changes in this state are driven by error
      feedback signals, which consist of the visually perceived reach error, the
      artificial shift in visual feedback, or both. Subjects correct for > or =20% of
      the error observed on each movement, despite being unaware of the visual shift.
      The state of adaptation is also driven by internal dynamics, consisting of a
      decay back to a baseline state and a "state noise" process. State noise includes
      any source of variability that directly affects the state of adaptation, such as
      variability in sensory feedback processing, the computations that drive learning,
      or the maintenance of the state. This noise is accumulated in the state across
      trials, creating temporal correlations in the sequence of reach errors. These
      correlations allow us to distinguish state noise from sensorimotor performance
      noise, which arises independently on each trial from random fluctuations in the
      sensorimotor pathway. We show that these two noise sources contribute comparably
      to the overall magnitude of movement variability. Finally, the dynamics of
      adaptation measured with random feedback shifts generalizes to the case of
      constant feedback shifts, allowing for a direct comparison of our results with
      more traditional blocked-exposure experiments.

PMID- 17202231
TI  - Cortical FMRI activation to sequences of tones alternating in frequency:
      relationship to perceived rate and streaming.
AB  - Human listeners were functionally imaged while reporting their perception of
      sequences of alternating-frequency tone bursts separated by 0, 1/8, 1, or 20
      semitones. Our goal was to determine whether functional magnetic resonance
      imaging (fMRI) activation of auditory cortex changes with frequency separation in
      a manner predictable from the perceived rate of the stimulus. At the null and
      small separations, the tones were generally heard as a single stream with a
      perceived rate equal to the physical tone presentation rate. fMRI activation in
      auditory cortex was appreciably phasic, showing prominent peaks at the sequence
      onset and offset. At larger-frequency separations, the higher- and lower
      frequency tones perceptually separated into two streams, each with a rate equal
      to half the overall tone presentation rate. Under those conditions, fMRI
      activation in auditory cortex was more sustained throughout the sequence duration
      and was larger in magnitude and extent. Phasic to sustained changes in fMRI
      activation with changes in frequency separation and perceived rate are comparable
      to, and consistent with, those produced by changes in the physical rate of a
      sequence and are far greater than the effects produced by changing other physical
      stimulus variables, such as sound level or bandwidth. We suggest that the neural
      activity underlying the changes in fMRI activation with frequency separation
      contribute to the coding of the co-occurring changes in perceived rate and
      perceptual organization of the sound sequences into auditory streams.

PMID- 17202233
TI  - Etomidate reduces initiation of backpropagating dendritic action potentials:
      implications for sensory processing and synaptic plasticity during anesthesia.
AB  - Anesthetics may induce specific changes that alter the balance of activity within
      neural networks. Here we describe the effects of the GABA(A) receptor
      potentiating anesthetic etomidate on sensory processing, studied in a cerebellum
      like structure, the electrosensory lateral line lobe (ELL) of mormyrid fish, in
      vitro. Previous studies have shown that the ELL integrates sensory input and
      removes predictable features by comparing reafferent sensory signals with a
      descending electromotor command-driven corollary signal that arrives in part
      through parallel fiber synapses with the apical dendrites of GABAergic
      interneurons. These synapses show spike timing-dependent depression when
      presynaptic activation is associated with postsynaptic backpropagating dendritic
      action potentials. Under etomidate, almost all neurons become tonically
      hyperpolarized. The threshold for action potential initiation increased for both
      synaptic activation and direct intracellular depolarization. Synaptically evoked
      inhibitory postsynaptic potentials (IPSPs) were also strongly potentiated and
      prolonged. Current source density analysis showed that backpropagation of action
      potentials through the apical dendritic arborization in the molecular layer was
      reduced but could be restored by increasing stimulus strength. These effects of
      etomidate were blocked by bicuculline or picrotoxin. It is concluded that
      etomidate affects both tonic and phasic inhibitory conductances at GABA(A)
      receptors and that increased shunting inhibition at the level of the proximal
      dendrites also contributes to increasing the threshold for action potential
      backpropagation. When stimulus strength is sufficient to evoke backpropagation,
      repetitive association of synaptic excitation with postsynaptic action potential
      initiation still results in synaptic depression, showing that etomidate does not
      interfere with the molecular mechanism underlying plastic modulation.

PMID- 17202234
TI  - Impact of experience on the representation of object-centered space in the
      macaque supplementary eye field.
AB  - Many neurons in the macaque supplementary eye field (SEF) exhibit object-centered
      spatial selectivity, firing at different rates when the monkey plans a saccade to
      the left or right end of a horizontal bar. Is this property natural to the SEF or
      is it a product of specialized training in the laboratory? To answer this
      question, we monitored the activity of single SEF neurons in two monkeys before
      and after training to select eye-movement targets by an object-centered rule.
      During stage 1, the monkeys performed a color delayed-match-to-sample (DMS) task
      in which a red or green central cue dictated an eye movement to the matching end
      of a horizontal bar. Many neurons at this stage exhibited object-centered spatial
      selectivity. During stage 2, the monkeys performed a color-conditional object
      centered task in which a green or red central cue instructed an eye movement to
      the left or right end of a gray bar. More neurons exhibited object-centered
      spatial selectivity during this stage than during stage 1. During stage 3, the
      monkeys again performed the color DMS task. The fraction of neurons exhibiting
      object-centered spatial selectivity remained at a level comparable to that
      observed during stage 2 and above that observed during stage 1. Thus object
      centered spatial selectivity was present before training on an object-centered
      rule, was enhanced as a product of object-centered training, and outlasted active
      use of an object-centered rule. We conclude that neural representations of object
      centered space, naturally present in the primate brain, can be sharpened by
      training.

PMID- 17202235
TI  - MAPK signaling pathways mediate AMPA receptor trafficking in an in vitro model of
      classical conditioning.
AB  - The mitogen-activated protein kinase (MAPK) signal transduction pathways have
      been implicated in underlying mechanisms of synaptic plasticity and learning.
      However, the differential roles of the MAPK family members extracellular signal
      regulated kinase (ERK) and p38 in learning remain to be clarified. Here, an in
      vitro model of classical conditioning was examined to assess the roles of ERK and
      p38 MAPK in this form of learning. Previous studies showed that NMDA-mediated
      trafficking of synaptic glutamate receptor 4 (GluR4)-containing AMPA receptors
      (AMPARs) underlies conditioning in this preparation and that this is accomplished
      through GluR4 interactions with the immediate-early gene protein Arc and the
      actin cytoskeleton. Here, it is shown that attenuation of conditioned responses
      (CRs) by ERK and p38 MAPK antagonists is associated with significantly reduced
      synaptic localization of GluR4 subunits. Western blotting reveals that p38 MAPK
      significantly increases its activation levels during late stages of conditioning
      during CR expression. In contrast, ERK MAPK activation is enhanced in early
      conditioning during CR acquisition. The results suggest that MAPKs have a central
      role in the synaptic delivery of GluR4-containing AMPARs during in vitro
      classical conditioning.

PMID- 17202232
TI  - BOLD coherence reveals segregated functional neural interactions when adapting to
      distinct torque perturbations.
AB  - In the natural world, we experience and adapt to multiple extrinsic
      perturbations. This poses a challenge to neural circuits in discriminating
      between different context-appropriate responses. Using event-related fMRI, we
      characterized the neural dynamics involved in this process by randomly delivering
      a position- or velocity-dependent torque perturbation to subjects' arms during a
      target-capture task. Each perturbation was color-cued during movement preparation
      to provide contextual information. Although trajectories differed between
      perturbations, subjects significantly reduced error under both conditions. This
      was paralleled by reduced BOLD signal in the right dentate nucleus, the left
      sensorimotor cortex, and the left intraparietal sulcus. Trials included "NoGo"
      conditions to dissociate activity related to preparation from execution and
      adaptation. Subsequent analysis identified perturbation-specific neural processes
      underlying preparation ("NoGo") and adaptation ("Go") early and late into
      learning. Between-perturbation comparisons of BOLD magnitude revealed negligible
      differences for both preparation and adaptation trials. However, a network-level
      analysis of BOLD coherence revealed that by late learning, response preparation
      ("NoGo") was attributed to a relative focusing of coherence within cortical and
      basal ganglia networks in both perturbation conditions, demonstrating a common
      network interaction for establishing arbitrary visuomotor associations.
      Conversely, late-learning adaptation ("Go") was attributed to a focusing of BOLD
      coherence between a cortical-basal ganglia network in the viscous condition and
      between a cortical-cerebellar network in the positional condition. Our findings
      demonstrate that trial-to-trial acquisition of two distinct adaptive responses is
      attributed not to anatomically segregated regions, but to differential functional
      interactions within common sensorimotor circuits.

PMID- 17202237
TI  - Role of adaptation in C. elegans thermotaxis. Focus on "Short-term adaptation and
      temporal processing in the cryophilic response of Caenorabditis elegans".

PMID- 17202236
TI  - What generates whisking? Focus on: "The whisking rhythm generator: a novel
      mammalian network for the generation of movement".

PMID- 17202238
TI  - Activity-dependent peptidergic modulation of the plateau-generating neuron B64 in
      the feeding network of Aplysia.
AB  - Many behaviors display various forms of activity-dependent plasticity. An example
      of such plasticity is the progressive shortening of the duration of protraction
      phase of feeding responses of Aplysia that occurs when feeding responses are
      repeatedly elicited. A similar protraction-duration shortening is observed in
      isolated ganglia of Aplysia when feeding-like motor programs are elicited through
      a prolonged stimulation of the command-like neuron CBI-2. Here, we investigate a
      cellular mechanism that may underlie this activity-dependent shortening of
      protraction duration of feeding motor programs. CBI-2 contains two neuropeptides,
      CP2 and FCAP. Previous work showed that CP2 shortens protraction duration of CBI
      2 elicited programs. We show here that the same is true for FCAP. We also show
      that both CP2 and FCAP modulated the biophysical properties of a plateau
      generating neuron, B64, that plays an important role in terminating the
      protraction phase of feeding motor programs. We find that prestimulation of CBI
      2, as well as superfusion of CP2 and FCAP, lowered the threshold for activation
      of the plateau potential in B64. The threshold-lowering actions of CBI-2
      prestimulation were occluded by superfusion of FCAP and CP2. Furthermore, at
      elevated temperature, conditions under which peptide release is prevented in
      Aplysia, prestimulation of CBI-2 does not lower the plateau-potential threshold,
      whereas superfusion of CP2 and FCAP does. Our findings are consistent with the
      hypothesis that peptides released from CBI-2 lower the threshold for activation
      of plateau potential in B64, thereby contributing to the shortening of
      protraction duration when CBI-2 is repeatedly activated.

PMID- 17202240
TI  - Changes in excitability of the cortical projections to the human tibialis
      anterior after paired associative stimulation.
AB  - Paired associative stimulation (PAS) based on Hebb's law of association can
      induce plastic changes in the intact human. The optimal interstimulus interval
      (ISI) between the peripheral nerve and transcranial magnetic stimulus is not
      known for muscles of the lower leg. The aims of this study were to investigate
      the effect of PAS for a variety of ISIs and to explore the efficacy of PAS when
      applied during dynamic activation of the target muscle. PAS was applied at 0.2 Hz
      for 30 min with the tibialis anterior (TA) at rest. The ISI was varied randomly
      in seven sessions (n = 5). Subsequently, PAS was applied (n = 14, ISI = 55 ms)
      with the TA relaxed or dorsi-flexing. Finally, an optimized ISI based on the
      subject somatosensory evoked potential (SEP) latency plus a central processing
      delay (6 ms) was used (n = 13). Motor-evoked potentials (MEPs) were elicited in
      the TA before and after the intervention, and the size of the TA MEP was
      extracted. ISIs of 45, 50, and 55 ms increased and 40 ms decreased TA MEP
      significantly (P = 0.01). PAS during dorsi-flexion increased TA MEP size by 92%
      (P = 0.001). PAS delivered at rest resulted in a nonsignificant increase;
      however, when the ISI was optimized from SEP latency recordings, all subjects
      showed significant increases (P = 0.002). No changes in MEP size occurred in the
      antagonist. Results confirm that the excitability of the corticospinal
      projections to the TA but not the antagonist can be increased after PAS. This is
      strongly dependent on the individualized ISI and on the activation state of the
      muscle.

PMID- 17202239
TI  - The whisking rhythm generator: a novel mammalian network for the generation of
      movement.
AB  - Using the rat vibrissa system, we provide evidence for a novel mechanism for the
      generation of movement. Like other central pattern generators (CPGs) that
      underlie many movements, the rhythm generator for whisking can operate without
      cortical inputs or sensory feedback. However, unlike conventional mammalian CPGs,
      vibrissa motoneurons (vMNs) actively participate in the rhythmogenesis by
      converting tonic serotonergic inputs into the patterned motor output responsible
      for movement of the vibrissae. We find that, in vitro, a serotonin receptor
      agonist, alpha-Me-5HT, facilitates a persistent inward current (PIC) and evokes
      rhythmic firing in vMNs. Within each motoneuron, increasing the concentration of
      alpha-Me-5HT significantly increases the both the magnitude of the PIC and the
      motoneuron's firing rate. Riluzole, which selectively suppresses the Na(+)
      component of PICs at low concentrations, causes a reduction in both of these
      phenomena. The magnitude of this reduction is directly correlated with the
      concentration of riluzole. The joint effects of riluzole on PIC magnitude and
      firing rate in vMNs suggest that the two are causally related. In vivo we find
      that the tonic activity of putative serotonergic premotoneurons is positively
      correlated with the frequency of whisking evoked by cortical stimulation. Taken
      together, these results support the hypothesized novel mammalian mechanism for
      movement generation in the vibrissa motor system where vMNs actively participate
      in the rhythmogenesis in response to tonic drive from serotonergic
      premotoneurons.

PMID- 17202241
TI  - Chronic high-inspired CO2 decreases excitability of mouse hippocampal neurons.
AB  - To examine the effect of chronically elevated CO(2) on excitability and function
      of neurons, we exposed mice to 8 and 12% CO(2) for 4 wk (starting at 2 days of
      age), and examined the properties of freshly dissociated hippocampal neurons
      obtained from slices. Chronic CO(2)-treated neurons (CC) had a similar input
      resistance (R(m)) and resting membrane potential (V(m)) as control (CON).
      Although treatment with 8% CO(2) did not change the rheobase (64 +/- 11 pA, n = 9
      vs. 47 +/- 12 pA, n = 8 for CC 8% vs. CON; means +/- SE), 12% CO(2) treatment
      increased it significantly (73 +/- 8 pA, n = 9, P = 0.05). Furthermore, the 12%
      CO(2) but not the 8% CO(2) treatment decreased the Na(+) channel current density
      (244 +/- 36 pA/pF, n = 17, vs. 436 +/- 56 pA/pF, n = 18, for CC vs. CON, P =
      0.005). Recovery from inactivation was also lowered by 12% but not 8% CO(2).
      Other gating properties of Na(+) current, such as voltage-conductance curve,
      steady-state inactivation, and time constant for deactivation, were not modified
      by either treatment. Western blot analysis showed that the expression of Na(+)
      channel types I-III was not changed by 8% CO(2) treatment, but their expression
      was significantly decreased by 20-30% (P = 0.03) by the 12% treatment. We
      conclude from these data and others that neuronal excitability and Na(+) channel
      expression depend on the duration and level of CO(2) exposure and maturational
      changes occur in early life regarding neuronal responsiveness to CO(2).

PMID- 17202243
TI  - Evaluating information transfer between auditory cortical neurons.
AB  - Transfer entropy, presented as a new tool for investigating neural assemblies,
      quantifies the fraction of information in a neuron found in the past history of
      another neuron. The asymmetry of the measure allows feedback evaluations. In
      particular, this tool has potential applications in investigating windows of
      temporal integration and stimulus-induced modulation of firing rate. Transfer
      entropy is also able to eliminate some effects of common history in spike trains
      and obtains results that are different from cross-correlation. The basic transfer
      entropy properties are illustrated with simulations. The information transfer
      through a network of 16 simultaneous multiunit recordings in cat's auditory
      cortex was examined for a large number of acoustic stimulus types. Application of
      the transfer entropy to a large database of multiple single-unit activity in
      cat's primary auditory cortex revealed that most windows of temporal integration
      found during spontaneous activity range between 2 and 15 ms. The normalized
      transfer entropy shows similarities and differences with the strength of cross
      correlation; these form the basis for revisiting the neural assembly concept.

PMID- 17202242
TI  - Distinct synaptic dynamics of heterogeneous pacemaker neurons in an oscillatory
      network.
AB  - Many rhythmically active networks involve heterogeneous populations of pacemaker
      neurons with potentially distinct synaptic outputs that can be differentially
      targeted by extrinsic inputs or neuromodulators, thereby increasing possible
      network output patterns. To understand the roles of heterogeneous pacemaker
      neurons, we characterized differences in synaptic output from the anterior
      burster (AB) and pyloric dilator (PD) neurons in the lobster pyloric network.
      These intrinsically distinct neurons are strongly electrically coupled, coactive,
      and constitute the pyloric pacemaker ensemble. During pyloric oscillations, the
      pacemaker neurons produce compound inhibitory synaptic connections to the
      follower lateral pyloric (LP) and pyloric constrictor (PY) neurons, which fire
      out of phase with AB/PD and with different delay times. Using pharmacological
      blockers, we separated the synapses originating from the AB and PD neurons and
      investigated their temporal dynamics. These synapses exhibited distinct short
      term dynamics, depending on the presynaptic neuron type, and had different
      relative contributions to the total synaptic output depending on waveform shape
      and cycle frequency. However, paired comparisons revealed that the amplitude or
      dynamics of synapses from either the AB or PD neuron did not depend on the
      postsynaptic neuron type, LP or PY. To address the functional implications of
      these findings, we examined the correlation between synaptic inputs from the
      pacemakers and the burst onset phase of the LP and PY neurons in the ongoing
      pyloric rhythm. These comparisons showed that the activity of the LP and PY
      neurons is influenced by the peak phase and amplitude of the synaptic inputs from
      the pacemaker neurons.

PMID- 17202244
TI  - Temporal properties of posterior parietal neuron discharges during working memory
      and passive viewing.
AB  - Working memory is mediated by the discharges of neurons in a distributed network
      of brain areas. It was recently suggested that enhanced rhythmicity in neuronal
      activity may be critical for sustaining remembered information. To test whether
      working memory is characterized by unique temporal discharge patterns, we
      analyzed the autocorrelograms and power spectra of spike trains recorded from the
      posterior parietal cortex of monkeys performing a visuospatial working-memory
      task. We compared the intervals of active memory maintenance and fixation and
      repeated the same analysis in spike trains from monkeys never trained to perform
      any kind of memory task. The most salient effect we observed was a decrease of
      power in the 5- to 10-Hz frequency range during the presentation of visual
      stimuli. This pattern was observed both in the working-memory condition and the
      control condition, although it was more prominent in the former, where it
      persisted after cue presentation when the monkeys actively remembered the spatial
      location of the stimulus. Low-frequency power suppression resulted from relative
      refractory periods that were significantly longer in the working-memory condition
      and presumably emerged from local-circuit inhibition. We also detected a spectral
      peak in the 15- to 20-Hz range, although this was more prominent during fixation
      than during the stimulus and working-memory periods. Our results are in line with
      previous reports in prefrontal cortex and indicate that unique temporal patterns
      of single-neuron firing characterize persistent delay activity, although these do
      not involve the appearance of enhanced oscillations.

PMID- 17202245
TI  - Modulation of human BCRP (ABCG2) activity by anti-HIV drugs.
AB  - OBJECTIVES: The safety and effectiveness of highly active antiretroviral therapy
      (HAART) is challenged by viral resistance to antiretrovirals and the frequent
      occurrence of drug interactions which may limit the access of these drugs to the
      target sites. In particular, drug distribution and elimination may be modified by
      active efflux transporters. While P-glycoprotein is well evaluated in this
      regard, the interaction of antiretrovirals with the ABC transporter BCRP (ABCG2)
      is far from being elucidated. The aim of this study was therefore to investigate
      the influence of all important anti-HIV drugs on BCRP activity in vitro in one
      assay to allow unrestricted comparison of the results. METHODS: BCRP inhibition
      was assessed by an increase in pheophorbide A accumulation in MDCKII-BCRP cells
      and compared with the corresponding parental cell line MDCKII lacking human BCRP.
      RESULTS: According to the IC(50) estimation, the rank order for BCRP inhibition
      was lopinavir > nelfinavir > delavirdine > efavirenz > saquinavir > atazanavir >
      amprenavir > abacavir. Whereas nevirapine and zidovudine exerted weak inhibition,
      the inhibitory potency for ritonavir and tipranavir could not be estimated due to
      their low solubility and all other tested compounds (indinavir, didanosine,
      emtricitabine, lamivudine, stavudine, tenofovir and zalcitabine) were devoid of
      an effect. CONCLUSIONS: Taken together, our study demonstrates significant
      inhibition of BCRP by many anti-HIV drugs. These results suggest that inhibition
      of BCRP might contribute to drug-drug interactions observed during HAART in vivo
      and possibly also the superior effectiveness of combination antiretroviral
      therapy.

PMID- 17202247
TI  - Uncoupling protein-3: clues in an ongoing mitochondrial mystery.
AB  - Uncoupling protein (UCP) 3 (UCP3) is a mitochondrial anion carrier protein with
      highly selective expression in skeletal muscle. Despite a great deal of interest,
      to date neither its molecular mechanism nor its biochemical and physiological
      functions are well understood. Based on its high degree of homology to the
      original UCP (UCP1), early studies examined a role for UCP3 in thermogenesis.
      However, evidence for such a function is lacking. Recent studies have focused on
      two distinct, but not mutually exclusive, hypotheses: 1) UCP3 mitigates reactive
      oxygen species (ROS) production, and 2) UCP3 is somehow involved in fatty acid
      (FA) translocation. While supportive evidence exists for both hypotheses, the
      interpretation of the corresponding evidence has created some controversy.
      Mechanistic studies examining mitigated ROS production have been largely
      conducted in vitro, and the physiological significance of the findings is
      questioned. Conversely, while physiological evidence exists for FA translocation
      hypotheses, the evidence is largely correlative, leaving causal relationships
      unexplored. This review critically assesses evidence for the hypotheses and
      attempts to link the outcomes from mechanistic studies to physiological
      implications. Important directions for future studies, using current and novel
      approaches, are discussed.

PMID- 17202246
TI  - Urearetics: a small molecule screen yields nanomolar potency inhibitors of urea
      transporter UT-B.
AB  - Functional studies in knockout mice indicate a critical role for urea
      transporters (UTs) in the urinary concentrating mechanism and in renal urea
      clearance. However, potent and specific urea transport blockers have not been
      available. Here, we used high-throughput screening to discover high-affinity,
      small molecule inhibitors of the UT-B urea transporter. A collection of 50,000
      diverse, drug-like compounds was screened using a human erythrocyte lysis assay
      based on UT-B-facilitated acetamide transport. Primary screening yielded
      approximately 30 UT-B inhibitors belonging to the phenylsulfoxyoxazole,
      benzenesulfonanilide, phthalazinamine, and aminobenzimidazole chemical classes.
      Screening of approximately 700 structurally similar analogs gave many active
      compounds, the most potent of which inhibited UT-B urea transport with an EC50 of
      approximately 10 nM, and approximately 100% inhibition at higher concentrations.
      Phenylsulfoxyoxazoles and phthalazinamines also blocked rodent UT-B and had good
      UT-B vs. UT-A specificity. The UT-B inhibitors did not reduce aquaporin-1 (AQP1)
      facilitated water transport. In AQP1-null erythrocytes, "chemical UT-B knockout"
      by UT-B inhibitors reduced by approximately 3-fold UT-B-mediated water transport,
      supporting an aqueous pore pathway through UT-B. UT-B inhibitors represent a new
      class of diuretics, "urearetics," which are predicted to increase renal water and
      solute clearance in water-retaining states.

PMID- 17202248
TI  - Early in vivo assessment of angiostatic therapy efficacy by molecular MRI.
AB  - Noninvasive diagnostic imaging methods to establish the efficacy of angiostatic
      therapies are becoming increasingly important with the first Food and Drug
      Administration approvals of such agents. Magnetic resonance molecular imaging is
      an imaging technique that allows the visualization of pathological processes in
      vivo with a better spatial resolution as compared with nuclear methods, such as
      photon emission tomography and single photon emission computed tomography. In
      this study, we used alpha(v)beta3 targeted bimodal liposomes to quantitate
      angiogenesis in a tumor mouse model with magnetic resonance imaging (MRI) and to
      evaluate the therapeutic efficacy of the angiogenesis inhibitors anginex and
      endostatin. The MRI findings were validated with fluorescence microscopy and
      showed a very good correlation with the microvessel density. In conclusion, this
      study provides evidence that molecular MRI can be used to noninvasively measure
      the efficacy of angiogenesis inhibitors during the course of therapy.

PMID- 17202249
TI  - Regulation of capacitative calcium entries by alpha1-syntrophin: association of
      TRPC1 with dystrophin complex and the PDZ domain of alpha1-syntrophin.
AB  - Calcium mishandling in Duchenne dystrophic muscle suggested that dystrophin, a
      membrane-associated cytoskeleton protein, might regulate calcium signaling
      cascade such as calcium influx pathway. It was previously shown that abnormal
      calcium entries involve uncontrolled stretch-activated currents and store
      operated Ca2+ currents supported by TRPC1 channels. Moreover, our recent work
      demonstrated that reintroduction of minidystrophin in dystrophic myotubes
      restores normal capacitative calcium entries (CCEs). However, until now, no
      molecular link between the dystrophin complex and calcium entry channels has been
      described. This study is the first to show by coimmunoprecipitation assays the
      molecular association of TRPC1 with dystrophin and alpha1-syntrophin in muscle
      cells. TRPC1 was also associated with alpha1-syntrophin in dystrophic muscle
      cells independently of dystrophin. Furthermore, glutathione S-transferase (GST)
      pull-down assays showed that TRPC1 binds to the alpha1-syntrophin PDZ domain.
      Transfected recombinant alpha1-syntrophin formed a complex with TRPC1 channels
      and restored normal CCEs in dystrophic muscle cells. We suggest that normal
      regulation of CCEs in skeletal muscle depends on the association between TRPC1
      channels and alpha1-syntrophin that may anchor the store-operated channels to the
      dystrophin-associated protein complex (DAPC). The loss of this molecular
      association could participate in the calcium alterations observed in dystrophic
      muscle cells. This study provides a new model for the regulation of calcium
      influx by interaction with the scaffold of the DAPC in muscle cells.

PMID- 17202250
TI  - VLA-4 blockade suppresses endotoxin-induced uveitis: in vivo evidence for
      functional integrin up-regulation.
AB  - Leukocyte adhesion to the vascular wall is a critical early step in the
      pathogenesis of inflammatory diseases and is mediated in part by the leukocyte
      integrin, VLA-4, which binds to endothelial vascular cell adhesion molecule
      (VCAM) -1. Here, we investigate VLA-4's role in endotoxin-induced uveitis (EIU).
      At various time points (6-48 h) after EIU induction, the severity of the
      inflammation was evaluated by quantifying cell and protein content in the aqueous
      fluid, firm leukocyte adhesion in the retinal vessels, and the number of
      extravasated leukocytes into the vitreous. Functional activation of VLA-4 in vivo
      was investigated in our previously introduced autoperfused micro flow chamber
      assay. Firm adhesion of EIU leukocytes to immobilized VCAM-1 under physiological
      blood flow conditions was significantly increased compared with normal controls
      (P<0.05), suggesting an important role for VLA-4 in EIU. VLA-4 blockade in vivo
      significantly suppressed all uveitis-related inflammatory parameters studied,
      decreasing the clinical score by 45% (P<0.01), protein content in the aqueous
      fluid by 21% (P<0.01), retinal leukostasis by 68% (P<0.01), and leukocyte
      accumulation in the vitreous by 75% (P<0.01). Our data provide novel evidence for
      functional up-regulation of VLA-4 during EIU and suggest VLA-4 blockade as a
      promising therapeutic strategy for treatment of acute inflammatory eye diseases.

PMID- 17202251
TI  - Current trends and controversies over pre-operative chemotherapy for women with
      operable breast cancer.
AB  - The multi-disciplinary approach, including surgery, chemotherapy, endocrine
      therapy and radiation therapy, has become the standard treatment for primary
      breast cancer patients. The indication of pre-operative chemotherapy has been
      extended to women with potentially operable breast cancer based on the results of
      large randomized studies and has become an attractive option that extends the
      chance of breast conservation. The clinical and pathological responses to pre
      operative chemotherapy correlates with long-term outcome. The anthracycline
      containing regimen is now considered the standard. Sequential administration of
      non-cross-resistant drugs, namely taxanes, improves local tumor response but its
      long-term benefit has been controversial. Prediction of response to pre-operative
      chemotherapy still remains a challenge. Identification of useful predictive
      markers and development of molecular-targeted drugs is the key to individualized
      therapy in the future.

PMID- 17202252
TI  - Lymphopenic mice reconstituted with limited repertoire T cells develop severe,
      multiorgan, Th2-associated inflammatory disease.
AB  - Lymphopenia and restricted T cell repertoires in humans are often associated with
      severe eosinophilic disease and a T cell Th2 bias. To examine the pathogenesis of
      this phenomenon, C57BL/6 Rag2-/- mice received limited (3 x 10(4)) or large (2 x
      10(6)) numbers of CD4 T cells. Three to 5 months after transfer, mice that had
      received 3 x 10(4) T cells, but not those that received 2 x 10(6), developed
      fulminant macrophage pneumonia with eosinophilia, Ym1 deposition, and
      methacholine-induced airway hyperresponsiveness, as well as eosinophilic
      gastritis; esophagitis and other organ damage occurred in some cases. Donor cells
      were enriched for IL-4, IL-5, and IL-13 producers. When 3 x 10(4) cells were
      transferred into CD3epsilon-/- hosts, the mice developed strikingly elevated
      serum IgE. Prior transfer of 3 x 10(5) CD25+ CD4 T cells into Rag2-/- recipients
      prevented disease upon subsequent transfer of CD25- CD4 T cells, whereas 3 x
      10(4) regulatory T cells (Tregs) did not, despite the fact that there were equal
      total numbers of Tregs in the host at the time of transfer of CD25- CD4 T cells.
      Limited repertoire complexity of Tregs may lead to a failure to control induction
      of immunopathologic responses, and limitation in repertoire complexity of
      conventional cells may be responsible for the Th2 phenotype.

PMID- 17202253
TI  - The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and
      contributes to the long survival of CD8 memory T cells.
AB  - We previously described unique features of the IL-15 receptor (IL-15R)alpha. IL
      15Ralpha by itself forms stable complexes with IL-15 on cell surfaces and
      presents IL-15 in trans to neighboring natural killer/T cells. Moreover, the
      membrane IL-15/IL-15Ralpha complexes (membIL-15) undergo endosomal
      internalization but survive lysosomal degradation, allowing the complexes to
      recycle back to the cell surface. Here, we show that membIL-15+ cells act as a
      persistent source of IL-15 for the surrounding microenvironment (intercellular
      reservoir effect). Additionally, membIL-15+ cells give rise to augmented
      retention of IL-15 in the circulation as well as in tissues. Curiously, IL-15
      retention was particularly associated with lungs, rather than with lymph nodes,
      in normal unstimulated mice, which correlated with the preferential homing of
      antigen-specific CD8 T cells to lungs during their contraction phase in an IL
      15Ralpha-dependent manner. Furthermore, membIL-15, unlike soluble IL-15, caused
      sustained IL-15 signal transduction in the target cells. Collectively, these
      characteristics define IL-15 as a unique cytokine with prolonged in vivo survival
      and sustained biological action on the target cells, which may account for the
      proposed persistent action of IL-15 that helps the long-term survival of
      functional CD8 memory T cells in vivo.

PMID- 17202254
TI  - Neural substrates of envisioning the future.
AB  - The ability to envision specific future episodes is a ubiquitous mental
      phenomenon that has seldom been discussed in the neuroscience literature. In this
      study, subjects underwent functional MRI while using event cues (e.g., Birthday)
      as a guide to vividly envision a personal future event, remember a personal
      memory, or imagine an event involving a familiar individual. Two basic patterns
      of data emerged. One set of regions (e.g., within left lateral premotor cortex;
      left precuneus; right posterior cerebellum) was more active while envisioning the
      future than while recollecting the past (and more active in both of these
      conditions than in the task involving imagining another person). These regions
      appear similar to those emerging from the literature on imagined (simulated)
      bodily movements. A second set of regions (e.g., bilateral posterior cingulate;
      bilateral parahippocampal gyrus; left occipital cortex) demonstrated
      indistinguishable activity during the future and past tasks (but greater activity
      in both tasks than the imagery control task); similar regions have been shown to
      be important for remembering previously encountered visual-spatial contexts.
      Hence, differences between the future and past tasks are attributed to
      differences in the demands placed on regions that underlie motor imagery of
      bodily movements, and similarities in activity for these two tasks are attributed
      to the reactivation of previously experienced visual-spatial contexts. That is,
      subjects appear to place their future scenarios in well known visual-spatial
      contexts. Our results offer insight into the fundamental and little-studied
      capacity of vivid mental projection of oneself in the future.

PMID- 17202255
TI  - Chloroplast biogenesis: the use of mutants to study the etioplast-chloroplast
      transition.
AB  - In angiosperm plants, the etioplast-chloroplast transition is light-dependent. A
      key factor in this process is the protochlorophyllide oxidoreductase A (PORA),
      which catalyzes the light-induced reduction of protochlorophyllide to
      chlorophyllide. The import pathway of the precursor protein prePORA into
      chloroplasts was analyzed in vivo and in vitro by using homozygous loss-of
      function mutants in genes coding for chlorophyllide a oxygenase (CAO) or for
      members of the outer-envelope solute-channel protein family of 16 kDa (OEP16),
      both of which have been implied to be key factors for the import of prePORA. Our
      in vivo analyses show that cao or oep16 mutants contain a normally structured
      prolamellar body that contains the protochlorophyllide holochrome. Furthermore,
      etioplasts from cao and oep16 mutants contain PORA protein as found by mass
      spectrometry. Our data demonstrate that both CAO and OEP16 are dispensable for
      chloroplast biogenesis and play no central role in the import of prePORA in vivo
      and in vitro as further indicated by protein import studies.

PMID- 17202256
TI  - Enhancement of learning and memory after activation of cerebral Rho GTPases.
AB  - The mechanism whereby the morphology and connectivity of the dendritic tree is
      regulated depends on an actin dynamics that, in turn, is controlled by Rho
      GTPases, a family of small GTP-binding proteins encompassing Rho, Rac, and Cdc42
      subfamilies. Cytotoxic necrotizing factor 1 (CNF1), a protein toxin from
      Escherichia coli, constitutively activates Rho GTPases, thus leading to
      remodeling of the actin cytoskeleton in intact cells. Here, we show that the
      modulation of cerebral RhoA and Rac1 activity induced by CNF1 in mice leads to
      (i) rearrangement of cerebral actin cytoskeleton, (ii) enhanced neurotransmission
      and synaptic plasticity, and (iii) improved learning and memory in various
      behavioral tasks. The effects persist for weeks and are not observed in mice
      treated with a recombinant CNF1, in which the enzymatic activity was abolished by
      substituting serine to cysteine at position 866. The results suggest that
      learning ability can be improved through pharmacological manipulation of neural
      connectivity.

PMID- 17202257
TI  - MAPK regulation of maternal and zygotic Notch transcript stability in early
      development.
AB  - Spatiotemporal modulation of the evolutionarily conserved, intercellular Notch
      signaling pathway is important in the development of many animals. Examples
      include the regulation of neural-epidermal fate decisions in neurogenic ectoderm
      of Drosophila and somitogenesis in vertebrate presomitic mesoderm. In both these
      and most other cases, it appears that Notch-class transmembrane receptors are
      ubiquitously expressed. Modulation of the pathway is achieved primarily by the
      localized expression of the activating ligand or by alteration of receptor
      specificity through a glycosyl transferase. In contrast, we present this report
      of an instance where the abundance of the Notch-class mRNA itself is dynamically
      regulated. Taking advantage of the long cell cycle of the two-cell-stage embryo
      of the leech Helobdella robusta, we show that this regulation is achieved at the
      levels of both transcript stability and transcription. Moreover, MAPK signaling
      plays a significant role in regulating accumulation of the transcript by virtue
      of its effect on Hro-notch mRNA stability. Intracellular injection of
      heterologous reporter mRNAs shows that the Hro-notch 3' UTR, containing seven AU
      rich elements, is key to regulating transcript stability. Thus, we show that
      regulation of the Notch pathway can occur at a previously underappreciated level,
      namely that of transcript stability. Given that AU-rich elements occur in the 3'
      UTR of Notch-class genes in Drosophila, human, and Caenorhabditis elegans,
      regulation of Notch signaling by modulation of mRNA levels may be operating in
      other animals as well.

PMID- 17202258
TI  - Promoting motions in enzyme catalysis probed by pressure studies of kinetic
      isotope effects.
AB  - Use of the pressure dependence of kinetic isotope effects, coupled with a study
      of their temperature dependence, as a probe for promoting motions in enzymatic
      hydrogen-tunneling reactions is reported. Employing morphinone reductase as our
      model system and by using stopped-flow methods, we measured the hydride transfer
      rate (a tunneling reaction) as a function of hydrostatic pressure and
      temperature. Increasing the pressure from 1 bar (1 bar = 100 kPa) to 2 kbar
      accelerates the hydride transfer reaction when both protium (from 50 to 161 s(-1)
      at 25 degrees C) and deuterium (12 to 31 s(-1) at 25 degrees C) are transferred.
      We found that the observed primary kinetic isotope effect increases with pressure
      (from 4.0 to 5.2 at 25 degrees C), an observation incompatible with the Bell
      correction model for hydrogen tunneling but consistent with a full tunneling
      model. By numerical modeling, we show that both the pressure and temperature
      dependencies of the reaction rates are consistent with the framework of the
      environmentally coupled tunneling model of Kuznetsov and Ulstrup [Kuznetsov AM,
      Ulstrup J (1999) Can J Chem 77:1085-1096], providing additional support for the
      role of a promoting motion in the hydride tunneling reaction in morphinone
      reductase. Our study demonstrates the utility of "barrier engineering" by using
      hydrostatic pressure as a probe for tunneling regimes in enzyme systems and
      provides added and independent support for the requirement of promoting motions
      in such tunneling reactions.

PMID- 17202259
TI  - Structural similarity between the flagellar type III ATPase FliI and F1-ATPase
      subunits.
AB  - Construction of the bacterial flagellum in the cell exterior proceeds at its
      distal end by highly ordered self-assembly of many different component proteins,
      which are selectively exported through the central channel of the growing
      flagellum by the flagellar type III export apparatus. FliI is the ATPase of the
      export apparatus that drives the export process. Here we report the 2.4 A
      resolution crystal structure of FliI in the ADP-bound form. FliI consists of
      three domains, and the whole structure shows extensive similarities to the alpha
      and beta subunits of F0F1-ATPsynthase, a rotary motor that drives the chemical
      reaction of ATP synthesis. A hexamer model of FliI has been constructed based on
      the F1-ATPase structure composed of the alpha3beta3gamma subunits. Although the
      regions that differ in conformation between FliI and the F1-alpha/beta subunits
      are all located on the outer surface of the hexamer ring, the main chain
      structures at the subunit interface and those surrounding the central channel of
      the ring are well conserved. These results imply an evolutionary relation between
      the flagellum and F0F1-ATPsynthase and a similarity in the mechanism between FliI
      and F1-ATPase despite the apparently different functions of these proteins.

PMID- 17202260
TI  - Direct observation in solution of a preexisting structural equilibrium for a
      mutant of the allosteric aspartate transcarbamoylase.
AB  - Many signaling and metabolic pathways rely on the ability of some of the proteins
      involved to undergo a substrate-induced transition between at least two
      structural states. Among the various models put forward to account for binding
      and activity curves of those allosteric proteins, the Monod, Wyman, and Changeux
      model for allostery theory has certainly been the most influential, although a
      central postulate, the preexisting equilibrium between the low-activity, low
      affinity quaternary structure and the high-activity, high-affinity quaternary
      structure states in the absence of substrates, has long awaited direct
      experimental substantiation. Upon substrate binding, allosteric Escherichia coli
      aspartate transcarbamoylase adopts alternate quaternary structures, stabilized by
      a set of interdomain and intersubunit interactions, which are readily
      differentiated by their solution x-ray scattering curves. Disruption of a salt
      link, which is observed only in the low-activity, low-affinity quaternary
      structure, between Lys-143 of the regulatory chain and Asp-236 of the catalytic
      chain yields a mutant enzyme that is in a reversible equilibrium between at least
      two states in the absence of ligand, a major tenet of the Monod, Wyman, and
      Changeux model. By using this mutant as a magnifying glass of the structural
      effect of ligand binding, a comparative analysis of the binding of carbamoyl
      phosphate (CP) and analogs points out the crucial role of the amine group of CP
      in facilitating the transition toward the high-activity, high-affinity quaternary
      state. Thus, the cooperative binding of aspartate in aspartate transcarbamoylase
      appears to result from the combination of the preexisting quaternary structure
      equilibrium with local changes induced by CP binding.

PMID- 17202261
TI  - Multiple aromatic side chains within a disordered structure are critical for
      transcription and transforming activity of EWS family oncoproteins.
AB  - Chromosomal translocations involving the N-terminal approximately 250 residues of
      the Ewings sarcoma (EWS) oncogene produce a group of EWS fusion proteins (EFPs)
      that cause several distinct human cancers. EFPs are potent transcriptional
      activators and interact with other proteins required for mRNA biogenesis,
      indicating that EFPs induce tumorigenesis by perturbing gene expression. Although
      EFPs were discovered more than a decade ago, molecular analysis has been greatly
      hindered by the repetitive EWS activation domain (EAD) structure, containing
      multiple degenerate hexapeptide repeats (consensus SYGQQS) with a conserved
      tyrosine residue. By exploiting total gene synthesis, we have been able to
      systematically mutagenize the EAD and determine the effect on transcriptional
      activation by EWS/ATF1 and cellular transformation by EWS/Fli1. In both assays,
      we find the following requirements for EAD function. First, multiple tyrosine
      residues are essential. Second, phenylalanine can effectively substitute for
      tyrosine, showing that an aromatic ring can confer EAD function in the absence of
      tyrosine phosphorylation. Third, there is little requirement for specific peptide
      sequences and, thus, overall sequence composition (and not the degenerate
      hexapeptide repeat) confers EAD activity. Consistent with the above findings, we
      also report that the EAD is intrinsically disordered. However, a sensitive
      computational predictor of natural protein disorder (PONDR VL3) identifies
      potential molecular recognition features that are tyrosine-dependent and that
      correlate well with EAD function. In summary we have uncovered several molecular
      features of the EAD that will impact future studies of the broader EFP family and
      molecular recognition by complex intrinsically disordered proteins.

PMID- 17202262
TI  - Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian
      behavior by the suprachiasmatic nuclei.
AB  - The suprachiasmatic nucleus (SCN), the brain's principal circadian pacemaker,
      coordinates adaptive daily cycles of behavior and physiology, including the
      rhythm of sleep and wakefulness. The cellular mechanism sustaining SCN circadian
      timing is well characterized, but the neurochemical pathways by which SCN neurons
      coordinate circadian behaviors remain unknown. SCN transplant studies suggest a
      role for (unidentified) secreted factors, and one potential candidate is the SCN
      neuropeptide prokineticin 2 (Prok2). Prok2 and its cognate prokineticin receptor
      2 (Prokr2/Gpcr73l1) are widely expressed in both the SCN and its neural targets,
      and Prok2 is light-regulated. Hence, they may contribute to cellular timing
      within the SCN, entrainment of the clock, and/or they may mediate circadian
      output. We show that a targeted null mutation of Prokr2 disrupts circadian
      coordination of the activity cycle and thermoregulation. Specifically, mice
      lacking Prokr2 lost precision in timing the onset of nocturnal locomotor
      activity; and under both a light/dark cycle and continuous darkness, there was a
      pronounced temporal redistribution of activity away from early to late circadian
      night. Moreover, the coherence of circadian behavior was significantly reduced,
      and nocturnal body temperature was depressed. Entrainment by light is not,
      however, dependent on Prokr2, and bioluminescence real-time imaging of
      organotypical SCN slices showed that the mutant SCN is fully competent as a
      circadian oscillator. We conclude that Prokr2 is not necessary for SCN cellular
      timekeeping or entrainment, but it is an essential link for coordination of
      circadian behavior and physiology by the SCN, especially in defining the onset
      and maintenance of circadian night.

PMID- 17202263
TI  - Crystal structure of the C-terminal domain of Ebola virus VP30 reveals a role in
      transcription and nucleocapsid association.
AB  - Transcription of the highly pathogenic Ebola virus depends on VP30, a
      nucleocapsid-associated Ebola virus-specific transcription factor. The
      transcription activator VP30 was shown to play an essential role in Ebola virus
      replication, most likely by stabilizing nascent mRNA. Here we present the crystal
      structure of the C-terminal domain (CTD) of VP30 (VP30(CTD)) at 2.0-A resolution.
      VP30(CTD) folds independently into a dimeric helical assembly. The VP30(CTD)
      dimers assemble into hexamers that are present in virions, by an oligomerization
      domain located in the N terminus of VP30. Mutagenesis of conserved charged amino
      acids on VP30(CTD) revealed that two regions, namely a basic cluster around Lys
      180 and Glu-197, are required for nucleocapsid interaction. However, only
      mutagenesis of the basic cluster was shown to impair transcription activation,
      suggesting that both processes are regulated independently. The structure and the
      mutagenesis results reveal a potential pocket for small-molecule inhibitors that
      might prevent VP30 activity and thus virus propagation as it has been shown
      previously by peptides, which interfere with VP30 homooligomerization.

PMID- 17202264
TI  - Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling
      in dilated and hypertrophic cardiomyopathy.
AB  - Physical activity protects against cardiovascular disease, and physiological
      cardiac hypertrophy associated with regular exercise is usually beneficial, in
      marked contrast to pathological hypertrophy associated with disease. The
      p110alpha isoform of phosphoinositide 3-kinase (PI3K) plays a critical role in
      the induction of exercise-induced hypertrophy. Whether it or other genes
      activated in the athlete's heart might have an impact on cardiac function and
      survival in a setting of heart failure is unknown. To examine whether progressive
      exercise training and PI3K(p110alpha) activity affect survival and/or cardiac
      function in two models of heart disease, we subjected a transgenic mouse model of
      dilated cardiomyopathy (DCM) to swim training, genetically crossed cardiac
      specific transgenic mice with increased or decreased PI3K(p110alpha) activity to
      the DCM model, and subjected PI3K(p110alpha) transgenics to acute pressure
      overload (ascending aortic constriction). Life-span, cardiac function, and
      molecular markers of pathological hypertrophy were examined. Exercise training
      and increased cardiac PI3K(p110alpha) activity prolonged survival in the DCM
      model by 15-20%. In contrast, reduced PI3K(p110alpha) activity drastically
      shortened lifespan by approximately 50%. Increased PI3K(p110alpha) activity had a
      favorable effect on cardiac function and fibrosis in the pressure-overload model
      and attenuated pathological growth. PI3K(p110alpha) signaling negatively
      regulated G protein-coupled receptor stimulated extracellular responsive kinase
      and Akt (via PI3K, p110gamma) activation in isolated cardiomyocytes. These
      findings suggest that exercise and enhanced PI3K(p110alpha) activity delay or
      prevent progression of heart disease, and that supraphysiologic activity can be
      beneficial. Identification of genes important for hypertrophy in the athlete's
      heart could offer new strategies for treating heart failure.

PMID- 17202266
TI  - The ci/bH moiety in the b6f complex studied by EPR: a pair of strongly
      interacting hemes.
AB  - X-band EPR features in the region of 90-150 mT have previously been attributed to
      heme ci of the b6 complex [Zhang H, Primak A, Bowman MK, Kramer DM, Cramer WA
      (2004) Biochemistry 43:16329-16336] and interpreted as arising from a high-spin
      species. However, the complexity of the observed spectrum is rather untypical for
      high-spin hemes. In this work, we show that addition of the inhibitor 2-n-nonyl-4
      hydroxyquinoline N-oxide largely simplifies heme ci's EPR properties. The
      spectrum in the presence of 2-n-nonyl-4-hydroxyquinoline N-oxide is demonstrated
      to be caused by a simple S = 5/2, rhombic species split by magnetic dipolar
      interaction (A(xx )= 7.5 mT) with neighboring heme bH. The large spacing of lines
      in the uninhibited system, by contrast, cannot be rationalized solely on the
      basis of magnetic dipolar coupling but is likely to encompass strong
      contributions from exchange interactions. The role of the H2O/OH- molecule
      bridging heme ci's Fe atom and heme bH's propionate side chain in mediating these
      interactions is discussed.

PMID- 17202265
TI  - WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells.
AB  - Recent studies have identified a subpopulation of highly tumorigenic cells with
      stem/progenitor cell properties from human breast cancers, and it has been
      suggested that stem/progenitor cells, which remain after breast cancer therapy,
      may give rise to recurrent disease. We hypothesized that progenitor cells are
      resistant to radiation, a component of conventional breast cancer therapy, and
      that that resistance is mediated at least in part by Wnt signaling, which has
      been implicated in stem cell survival. To test this hypothesis, we investigated
      radioresistance by treating primary BALB/c mouse mammary epithelial cells with
      clinically relevant doses of radiation and found enrichment in normal progenitor
      cells (stem cell antigen 1-positive and side population progenitors). Radiation
      selectively enriched for progenitors in mammary epithelial cells isolated from
      transgenic mice with activated Wnt/beta-catenin signaling but not for background
      matched controls, and irradiated stem cell antigen 1-positive cells had a
      selective increase in active beta-catenin and survivin expression compared with
      stem cell antigen 1-negative cells. In clonogenic assays, colony formation in the
      stem cell antigen 1-positive progenitors was unaffected by clinically relevant
      doses of radiation. Radiation also induced enrichment of side population
      progenitors in the human breast cancer cell line MCF-7. These data demonstrate
      that, compared with differentiated cells, progenitor cells have different cell
      survival properties that may facilitate the development of targeted
      antiprogenitor cell therapies.

PMID- 17202267
TI  - Searching with iterated maps.
AB  - In many problems that require extensive searching, the solution can be described
      as satisfying two competing constraints, where satisfying each independently does
      not pose a challenge. As an alternative to tree-based and stochastic searching,
      for these problems we propose using an iterated map built from the projections to
      the two constraint sets. Algorithms of this kind have been the method of choice
      in a large variety of signal-processing applications; we show here that the scope
      of these algorithms is surprisingly broad, with applications as diverse as
      protein folding and Sudoku.

PMID- 17202269
TI  - Contrasts between Antarctic and Arctic ozone depletion.
AB  - This work surveys the depth and character of ozone depletion in the Antarctic and
      Arctic using available long balloon-borne and ground-based records that cover
      multiple decades from ground-based sites. Such data reveal changes in the range
      of ozone values including the extremes observed as polar air passes over the
      stations. Antarctic ozone observations reveal widespread and massive local
      depletion in the heart of the ozone "hole" region near 18 km, frequently
      exceeding 90%. Although some ozone losses are apparent in the Arctic during
      particular years, the depth of the ozone losses in the Arctic are considerably
      smaller, and their occurrence is far less frequent. Many Antarctic total
      integrated column ozone observations in spring since approximately the 1980s show
      values considerably below those ever observed in earlier decades. For the Arctic,
      there is evidence of some spring season depletion of total ozone at particular
      stations, but the changes are much less pronounced compared with the range of
      past data. Thus, the observations demonstrate that the widespread and deep ozone
      depletion that characterizes the Antarctic ozone hole is a unique feature on the
      planet.

PMID- 17202268
TI  - Postnatal lymphatic partitioning from the blood vasculature in the small
      intestine requires fasting-induced adipose factor.
AB  - Lymphatic vessels develop from specialized venous endothelial cells. Using
      knockout mice, we found that fasting-induced adipose factor (Fiaf) is required
      for functional partitioning of postnatal intestinal lymphatic and blood vessels.
      In wild-type animals, levels of intestinal Fiaf expression rise during the first
      postnatal day and peak at day 2, which coincides with the onset of the lymphatico
      venous partitioning abnormality in Fiaf-/- mutants on a mixed 129/SvJ:C57BL/6
      genetic background. Fiaf deficiency is not associated with disruption of the
      blood vasculature or with lymphatic endothelial recruitment of smooth muscle
      cells. We identified Prox1, a critical regulator of lymphangiogenesis, as a
      downstream target for Fiaf signaling in the intestinal lymphatic endothelium.
      This organ-specific lymphovascular abnormality can be rescued by allowing
      embryonic Fiaf-/- intestinal isografts to develop in Fiaf+/+ recipients.

PMID- 17202271
TI  - Evidence for last interglacial chronology and environmental change from Southern
      Europe.
AB  - Establishing phase relationships between earth-system components during periods
      of rapid global change is vital to understanding the underlying processes. It
      requires records of each component with independent and accurate chronologies.
      Until now, no continental record extending from the present to the penultimate
      glacial had such a chronology to our knowledge. Here, we present such a record
      from the annually laminated sediments of Lago Grande di Monticchio, southern
      Italy. Using this record we determine the duration (17.70 +/- 0.20 ka) and age of
      onset (127.20 +/- 1.60 ka B.P.) of the last interglacial, as reflected by
      terrestrial ecosystems. This record also reveals that the transitions at the
      beginning and end of the interglacial spanned only approximately 100 and 150
      years, respectively. Comparison with records of other earth-system components
      reveals complex leads and lags. During the penultimate deglaciation phase
      relationships are similar to those during the most recent deglaciation, peaks in
      Antarctic warming and atmospheric methane both leading Northern Hemisphere
      terrestrial warming. It is notable, however, that there is no evidence at
      Monticchio of a Younger Dryas-like oscillation during the penultimate
      deglaciation. Warming into the first major interstadial event after the last
      interglacial is characterized by markedly different phase relationships to those
      of the deglaciations, warming at Monticchio coinciding with Antarctic warming and
      leading the atmospheric methane increase. Diachroneity is seen at the end of the
      interglacial; several global proxies indicate progressive cooling after
      approximately 115 ka B.P., whereas the main terrestrial response in the
      Mediterranean region is abrupt and occurs at 109.50 +/- 1.40 ka B.P.

PMID- 17202270
TI  - Structural insights into the p97-Ufd1-Npl4 complex.
AB  - p97/VCP (Cdc48 in yeast) is an essential and abundant member of the AAA+ family
      of ATPases and is involved in a number of diverse cellular pathways through
      interactions with different adaptor proteins. The two most characterized adaptors
      for p97 are p47 and the Ufd1 (ubiquitin fusion degradation 1)-Npl4 (nuclear
      protein localization 4) complex. p47 directs p97 to membrane fusion events and
      has been shown to be involved in protein degradation. The Ufd1-Npl4 complex
      directs p97 to an essential role in endoplasmic reticulum-associated degradation
      and an important role in mitotic spindle disassembly postmitosis. Here we
      describe the structural features of the Ufd1-Npl4 complex and its interaction
      with p97 with the aid of EM and other biophysical techniques. The Ufd1-Npl4
      heterodimer has an elongated bilobed structure that is approximately 80 x 30 A in
      dimension. One Ufd1-Npl4 heterodimer is shown to interact with one p97 hexamer to
      form the p97-Ufd1-Npl4 complex. The Ufd1-Npl4 heterodimer emanates from one
      region on the periphery of the N-D1 plane of the p97 hexamer. Intriguingly, the
      p97-p47 and the p97-Ufd1-Npl4 complexes are significantly different in
      stoichiometry, symmetry, and quaternary arrangement, reflecting their specific
      actions and their ability to interact with additional cofactors that cooperate
      with p97 in diverse cellular pathways.

PMID- 17202272
TI  - Cultivation-independent analysis of changes in bacterial vaginosis flora
      following metronidazole treatment.
AB  - PCR was used to survey bacterial vaginosis flora before and after metronidazole
      treatment. The species composition for pretreatment patients was variable.
      Lactobacillus iners was prominent in all patients posttreatment. Atopobium
      vaginae concentrations were highest for patients who failed or responded
      incompletely to treatment and lowest for patients who were cured.

PMID- 17202273
TI  - Characteristics of the m2000 automated sample preparation and multiplex real-time
      PCR system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae.
AB  - We evaluated a new real-time PCR-based prototype assay for the detection of
      Chlamydia trachomatis and Neisseria gonorrhoeae developed by Abbott Molecular
      Inc. This assay is designed to be performed on an Abbott m2000 real-time
      instrument system, which consists of an m2000sp instrument for sample preparation
      and an m2000rt instrument for real-time PCR amplification and detection. The
      limit of detection of this prototype assay was determined to be 20 copies of
      target DNA for both C. trachomatis and N. gonorrhoeae, using serially diluted
      linearized plasmids. No cross-reactivity could be detected when 55 nongonococcal
      Neisseria isolates and 3 non-C. trachomatis Chlamydia isolates were tested at 1
      million genome equivalents per reaction. Concordance with the Roche Amplicor,
      BDProbeTec ET, and Gen-Probe APTIMA Combo 2 tests was assessed using
      unlinked/deidentified surplus clinical specimens previously analyzed with these
      tests. For C. trachomatis, concordance for positive results ranged from 93.7% to
      100%, while concordance for negative results ranged from 98.2% to 100%. For N.
      gonorrhoeae, concordance for positive and negative results ranged from 91.4% to
      100% and 99.3% to 100%, respectively. A workflow analysis of the prototype assay
      was conducted to obtain information on throughput under laboratory conditions. At
      48 samples/run, the time to first result for both C. trachomatis and N.
      gonorrhoeae was 4.5 h. A total of 135 patient specimens could be analyzed in 8.9
      h, with 75 min of hands-on time. This study demonstrated the technical and
      clinical feasibility of the new Abbott real-time PCR C. trachomatis/N.
      gonorrhoeae assay.

PMID- 17202274
TI  - Frequent in vitro recombination in internal transcribed spacers 1 and 2 during
      genotyping of Pneumocystis jirovecii.
AB  - Pneumocystis jirovecii is the causative agent of Pneumocystis pneumonia (PCP) in
      immunocompromised persons. Knowledge of the transmission and epidemiology of PCP
      is still incipient, and investigations on these subjects are based exclusively on
      applications of molecular typing techniques. The polymorphic internal transcribed
      spacers ITS1 and ITS2 in the ribosomal DNA operon, which in the P. jirovecii
      genome exist as single-copy DNA, are commonly used as target loci for isolate
      typing. In the course of genotyping P. jirovecii in respiratory specimens from
      PCP patients by amplification and cloning of a large number of ITS sequences, we
      found mixed infections (two or more types) in 50% of the samples. In a majority
      of the specimens with mixed infections, we detected many ITS haplotypes
      (combinations of ITS1 and ITS2 types) that appeared to be products of
      recombination between globally common ITS haplotypes present in the same sample.
      Here we present results of a series of experiments showing that essentially all
      ITS recombinants are chimeras formed during the genotyping process. Under
      standard conditions, as many as 37% of the amplified sequences could be hybrid
      DNA artifacts. We show that by modifying PCR amplification conditions, ITS
      chimera formation could be largely abolished and the erroneous establishment of
      artifactual haplotypes avoided. The accurate assessment of genetic diversity is
      fundamental for a better understanding of the epidemiology and biology of P.
      jirovecii infections.

PMID- 17202275
TI  - Identification of the capsular polysaccharides in Staphylococcus aureus clinical
      isolates by PCR and agglutination tests.
AB  - Staphylococcus aureus is a major cause of nosocomial and community-acquired
      infections. The predominance of two capsular polysaccharides, types 5 and 8, on
      the surface of clinical isolates led to the development of a conjugate vaccine
      (StaphVAX) based on capsular polysaccharides types 5 and 8 conjugated to a
      carrier protein. We have studied the capsular phenotypes and genotypes of 195
      isolates representative of all clinical syndromes that encompassed both hospital
      and community-acquired infections. These isolates were mainly detected in France
      between January 2001 and December 2004. In this population, most of clinical
      isolates (87%) expressed either capsular polysaccharide type 5 (42%) or 8 (45%),
      whereas 13% were nontypeable by the serotyping method with antibodies specific to
      capsular polysaccharide type 5 or 8. These 26 nontypeable strains were further
      serotyped and were demonstrated to express the cell wall surface antigen 336, a
      polyribitol phosphate N-acetylglucosamine, which resembles cell wall teichoic
      acid. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, we found
      a predominance of serotype 5 for 64% of strains, whereas MSSA isolates were
      predominantly capsular serotype 8 (60%). All S. aureus clinical isolates included
      in the present study have been investigated by PCR method, demonstrating that all
      isolates carried either the cap5 or the cap8 locus.

PMID- 17202276
TI  - First case of osteomyelitis caused by "Staphylococcus pettenkoferi".
AB  - "Staphylococcus pettenkoferi" (proposed name) was identified as an unusual agent
      of osteomyelitis in a diabetic foot infection. The phenotypical tests used failed
      to give a good identification. Molecular 16S rRNA gene and rpoB sequencing
      allowed us to correctly identify this new species of coagulase-negative
      staphylococcus responsible for this chronic infection.

PMID- 17202277
TI  - Use of outer surface protein repeat regions for improved genotyping of
      Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis is an important nosocomial pathogen, but little is
      known of its epidemiology. Accurate, reproducible typing systems would greatly
      improve epidemiologic investigations of S. epidermidis. The sequence-based typing
      technique most recently evaluated, multilocus sequence typing (MLST), often lacks
      discrimination and can be expensive. PCR and sequence-based analyses of the
      serine-aspartate repeat region of sdrG (Fbe) and the repeat region of the
      accumulation-associated protein gene (aap) were evaluated for the ability to
      discriminate among previously well-characterized S. epidermidis clinical
      isolates. Forty-eight strains were investigated, with sdrG found in 100% and aap
      found in 79% of all strains tested. Both genes demonstrated PCR product size and
      nucleotide sequence variation. Each system by itself gave an index of
      discrimination similar in value to that of MLST (0.924 and 0.953 compared to
      0.96), but discrimination was further improved when combinations of the three
      systems were used. We conclude that typing systems using amino acid and
      nucleotide repeat regions of the S. epidermidis surface proteins SdrG and Aap
      show promise as typing tools and should be investigated using a larger panel of
      clinically relevant isolates.

PMID- 17202278
TI  - Pulsed-field gel electrophoresis (PFGE) analysis of temporally matched Listeria
      monocytogenes isolates from human clinical cases, foods, ruminant farms, and
      urban and natural environments reveals source-associated as well as widely
      distributed PFGE types.
AB  - A total of 495 temporally and geographically matched Listeria monocytogenes
      isolates from human clinical cases, foods, ruminant farms, and urban and natural
      environments were used to investigate L. monocytogenes pulsed-field gel
      electrophoresis (PFGE) type diversity. Two-enzyme (AscI and ApaI) PFGE
      discriminated 310 PFGE types and exhibited higher overall discriminatory power
      (Simpson's index of discrimination [D] = 0.995) than either EcoRI ribotyping (D =
      0.950) or AscI or ApaI single-enzyme PFGE (D = 0.992 for both). Seven PFGE types
      showed significant associations with specific sources, including one and four
      PFGE types, respectively, associated with human clinical cases and foods. Spatial
      analysis of 13 PFGE types occurring >5 times showed that two PFGE types were
      specific to a single processing facility each, where they appear to have
      persisted over time. Nine PFGE types were geographically widespread and occurred
      among isolates from multiple sources. For example, a PFGE type that matched
      isolates from listeriosis outbreaks in Los Angeles and Switzerland occurred among
      isolates from farms (n = 7), human clinical cases (n = 4), environmental sources
      (n = 3), and foods (n = 1). Our data indicate that (i) PFGE is highly
      discriminatory for the subtyping of L. monocytogenes, (ii) some L. monocytogenes
      PFGE types are associated with specific sources, and (iii) some L. monocytogenes
      PFGE types are widely distributed and appear to be stable and pandemic. Large
      PFGE type databases representing isolates from different sources are thus needed
      to appropriately interpret subtype data in epidemiological investigations and to
      identify common as well as source-specific PFGE types.

PMID- 17202279
TI  - Comparative evaluation of Etest and sensititre yeastone panels against the
      Clinical and Laboratory Standards Institute M27-A2 reference broth microdilution
      method for testing Candida susceptibility to seven antifungal agents.
AB  - To assess their utility for antifungal susceptibility testing in our clinical
      laboratory, the Etest and Sensititre methods were compared with the Clinical and
      Laboratory Standards Institute (CLSI) M27-A2 reference broth microdilution
      method. Fluconazole (FL), itraconazole (I), voriconazole (V), posaconazole (P),
      flucytosine (FC), caspofungin (C), and amphotericin B (A) were tested with 212
      Candida isolates. Reference MICs were determined after 48 h of incubation, and
      Etest and Sensititre MICs were determined after 24 h and 48 h of incubation.
      Overall, excellent essential agreement (EA) between the reference and test
      methods was observed for Etest (95%) and Sensititre (91%). Etest showed an
      >or=92% EA for MICs for all drugs tested; Sensititre showed a >or=92% EA for MICs
      for I, FC, A, and C but 82% for FL and 85% for V. The overall categorical
      agreement (CA) was 90% for Etest and 88% for Sensititre; minor errors accounted
      for the majority of all categorical errors for both systems. Categorical
      agreement was lowest for Candida glabrata and Candida tropicalis with both test
      systems. Etest and Sensititre provided better CA at 24 h compared to 48 h for C.
      glabrata; however, CA for C. glabrata was <80% for FL with both test systems
      despite MIC determination at 24 h. Agreement between technologists for both
      methods was >or=98% for each agent against all organisms tested. Overall, Etest
      and Sensititre methods compared favorably with the CLSI reference method for
      determining the susceptibility of Candida. However, further evaluation of their
      performance for determining the MICs of azoles, particularly for C. glabrata, is
      warranted.

PMID- 17202280
TI  - Age- and serogroup-related differences in observed durations of nasopharyngeal
      carriage of penicillin-resistant pneumococci.
AB  - Using data from an ongoing Swedish intervention project, the observed durations
      of nasopharyngeal carriage of penicillin-nonsusceptible Streptococcus pneumoniae
      (PNSP) (MIC of penicillin G of >or=0.5 microg/ml) stratified by both pneumococcal
      serogroup and age of the carrier were compared. The means and 95% confidence
      intervals (CIs) were estimated by fitting a gamma distribution to the observed
      duration of carriage for each age and serogroup stratum. The mean observed
      duration of carriage for all cases was 37 days (95% CI, 35 to 38 days). Children
      below the age of 5 years carried PNSP for significantly longer periods (43 days;
      95% CI, 41 to 45 days) compared with older individuals (25 days; 95% CI, 24 to 27
      days). There were also differences within the group of cases below the age of 5
      years, as the duration of carriage became significantly shorter for each
      increasing age step: <1, 1 to 2, and 3 to 4 years. In addition, patients <5 years
      of age carried serogroups 9 and 14 for significantly shorter periods than groups
      6 and 23. Serogroup 9 was also carried for significantly shorter periods than
      group 19. For patients aged 5 years or older, no significant difference in
      carriage duration for different ages or serogroups could be noted. As young
      children have the longest duration of PNSP carriage, interventions aiming to
      reduce the prevalence in this group are of great importance. The results
      highlight the importance of taking both serogroup and age of the carriers into
      account when studying the dynamics of pneumococcal transmission in young
      children.

PMID- 17202281
TI  - Validation of laboratory screening criteria for herpes simplex virus testing of
      cerebrospinal fluid.
AB  - Most patients with herpes simplex virus (HSV) central nervous system (CNS)
      infection have abnormal cerebrospinal fluid (CSF) indices. Therefore, we
      implemented screening criteria based on CSF values and host immune status to
      guide testing. All CSF samples submitted for HSV PCR analysis from January 1999
      through December 2004 were included in the study. Specimens from patients with
      human immunodeficiency virus, a history of transplants, an age of <2 years, a CSF
      white blood cell count of >5 cells/mm(3), or a protein level of >50 mg/dl were
      tested upon request. All other samples were rejected and frozen. To validate our
      screening criteria, rejected specimens were pooled and tested retrospectively.
      Electronic medical records were also reviewed. A total of 1,659 HSV PCR requests
      from 1,458 patients were screened. Of the 1,296 specimens (78.1%) accepted for
      testing, 1,213 were negative, 7 were positive for HSV type 1 (HSV-1), 26 were
      positive for HSV-2, and 50 had unavailable results. Sixteen requests were
      rejected because an alternative microbiologic diagnosis had been established. Of
      the 347 samples rejected based on criteria, 222 (64.0%) remained available for
      pooled testing. No HSV-1-positive samples were identified in the rejected
      specimens. Two rejected specimens tested positive for HSV-2 DNA, but both met
      acceptance criteria which had not been communicated to the laboratory. Few
      patients (7.8%) with rejected specimens were treated with acyclovir, which
      suggests a low clinical concern for HSV encephalitis. Acceptance criteria based
      on CSF parameters and host immune status saved time and cost and did not miss
      patients with HSV CNS infection. Communication between the clinician and the
      laboratory is imperative for a successful screening program.

PMID- 17202282
TI  - Use of the Agilent 2100 bioanalyzer for rapid and reproducible molecular typing
      of Streptococcus pneumoniae.
AB  - Restriction fragment length polymorphism (RFLP) analysis is an economic and fast
      technique for molecular typing but has the drawback of difficulties in accurately
      sizing DNA fragments and comparing banding patterns on agarose gels. We aimed to
      improve RFLP for typing of the important human pathogen Streptococcus pneumoniae
      and to compare the results with the commonly used typing techniques of pulsed
      field gel electrophoresis and multilocus sequence typing. We designed primers to
      amplify a noncoding region adjacent to the pneumolysin gene. The PCR product was
      digested separately with six restriction endonucleases, and the DNA fragments
      were analyzed using an Agilent 2100 bioanalyzer for accurate sizing. The combined
      RFLP results for all enzymes allowed us to assign each of the 47 clinical
      isolates of S. pneumoniae tested to one of 33 RFLP types. RFLP analyzed using the
      bioanalyzer allowed discrimination between strains similar to that obtained by
      the more commonly used techniques of pulsed-field gel electrophoresis, which
      discriminated between 34 types, and multilocus sequence typing, which
      discriminated between 35 types, but more quickly and with less expense. RFLP of a
      noncoding region using the Agilent 2100 bioanalyzer could be a useful addition to
      the molecular typing techniques in current use for S. pneumoniae, especially as a
      first screen of a local population.

PMID- 17202283
TI  - Evaluation of the Merlin MICRONAUT system for rapid direct susceptibility testing
      of gram-positive cocci and gram-negative bacilli from positive blood cultures.
AB  - Bloodstream infections are life-threatening conditions which require the timely
      initiation of appropriate antimicrobial therapy. We evaluated the automated
      Merlin MICRONAUT system for rapid direct microtiter broth antimicrobial
      susceptibility testing (AST) of gram-positive cocci and gram-negative bacilli
      from BACTEC 9240 bottles with positive blood cultures in comparison to the
      standard method for the Merlin MICRONAUT system. This prospective study was
      conducted under routine working conditions during a 9-month period. Altogether,
      504 isolates from 409 patients and 11,819 organism-antibiotic combinations were
      evaluated for comparison of direct and standard AST methods. For gram-negative
      bacilli, direct and standard AST of 110 isolates was evaluated and MIC agreement
      was found for 98.1% of 2,637 organism-antibiotic combinations. Category
      (susceptible, intermediate susceptible, resistant [SIR]) agreement was found for
      99.0%, with results for 0.04% of combinations showing very major errors, those
      for 0.2% showing major errors, and those for 0.8% showing minor errors. For gram
      positive cocci, 373 isolates were evaluated and MIC agreement was found for 95.6%
      of 8,951 organism-antibiotic combinations. SIR agreement was found for 98.8%,
      with results for 0.3% of combinations showing very major errors, those for 0.4%
      showing major errors, and those for 0.5% showing minor errors. Although the
      number of tested isolates was limited (n = 33), direct AST of streptococci was
      performed for the first time, yielding promising results with SIR agreement for
      98.6% of 363 organism-antibiotic combinations. In conclusion, direct AST of gram
      negative bacilli and gram-positive cocci from positive blood cultures with the
      MICRONAUT system is a reliable technique that allows for the omission of repeat
      testing of subcultured isolates. Thereby, it reduces the time to results of blood
      culture testing and may have a positive impact on patient care.

PMID- 17202284
TI  - Maternal cocaine administration causes an epigenetic modification of protein
      kinase Cepsilon gene expression in fetal rat heart.
AB  - Protein kinase Cepsilon (PKCepsilon) plays a pivotal role in cardioprotection
      during cardiac ischemia and reperfusion injury. Recent studies demonstrated that
      prenatal cocaine exposure caused a decrease in PKCepsilon expression and
      increased heart susceptibility to ischemic injury in adult offspring, suggesting
      an in utero programming of PKCepsilon gene expression pattern in the heart. The
      present investigation aimed to elucidate whether an epigenetic mechanism, DNA
      methylation, accounts for cocaine-mediated repression of the PKCepsilon gene in
      the heart. Pregnant rats were administered either saline or cocaine
      intraperitoneally (15 mg/kg) twice daily from days 15 to 20 of gestational age,
      and term fetal hearts were studied. Cocaine treatment significantly decreased
      PKCepsilon mRNA and protein levels in the heart. CpG dinucleotides found in cAMP
      response element-binding protein (CREB), CREB/c-Jun1, and CREB/c-Jun2 binding
      sites at the proximal promoter region of the PKCepsilon gene were densely
      methylated and were not affected by cocaine. In contrast, methylation of CpGs in
      the activator protein 1 (AP-1) binding sites was low but was significantly
      increased by cocaine. Reporter gene assays showed that the AP-1 binding site
      played a strong stimulatory role of PKCepsilon gene transcription. Methylation of
      the AP-1 binding sites significantly decreased AP-1 binding to the PKCepsilon
      promoter. Supershift analyses implicated c-Jun homodimers binding to the AP-1
      binding sites. Cocaine did not affect nuclear c-Jun levels or the binding of c
      Jun to the unmethylated AP-1 binding sites. The results indicate a role for DNA
      methylation in cocaine-mediated PKCepsilon gene repression in the developing
      heart and suggest an epigenetic mechanism affecting this gene linked with
      vulnerability of ischemic injury in the heart of adult offspring.

PMID- 17202285
TI  - Haplotype thinking in lung disease.
AB  - To identify the genetic etiology of a disease of interest, disease-related
      characteristics (phenotypes) are often tested for association with genetic
      variants (genotypes). Although genetic association studies of single genetic
      variants have been widely performed, there has been increasing interest in
      studies of multiple adjacent genetic variants on one chromosome, known as a
      haplotype. In this review, we will provide background about the origin of
      haplotypes and why they can be useful in genetic studies; we will discuss
      approaches to determining haplotypes and performing haplotype-based genetic
      association studies; and we will compare single variant and haplotype-based
      approaches.

PMID- 17202286
TI  - A proteomic primer for the clinician.
AB  - Proteomics is a rapidly developing field and it opens new horizons in many
      research areas of life sciences. In the field of medicine, proteomics promises to
      accelerate the discovery of new drug targets and protein disease markers useful
      for in vitro diagnosis. In this article, we review the current proteomics
      technologies for biomarker discovery and validation, which include two
      dimensional gel electrophoresis, one- and two-dimensional liquid chromatography,
      and proteomic microarrays. We will also review proteomic strategies for protein
      protein interactions and identification of post-translational modifications.
      Selection of the more effective technology or combination of technologies is
      required to maximize the interpretation and utility of the data.

PMID- 17202288
TI  - Gene-environment interactions in asthma: with apologies to William of Ockham.
AB  - Many environmental factors and a large number of genetic polymorphisms have been
      reported to be associated with asthma risk in different locales and at different
      ages. It seems that what we call asthma is a heterogeneous set of conditions for
      which the only common feature is recurrent airway obstruction that is at least
      partially responsive to usual asthma therapy. Recent studies in which
      environmental factors and genetic variants were studied concomitantly have
      suggested a potential unifying concept for the disease. It seems that asthma is a
      genetically mediated development dysregulation of diverse immune and airway
      responses to a variety of specific and nonspecific exposures. It thus seems
      improbable that most genetic variants associated with asthma influence the
      disease regardless of which environmental factors trigger it and at which
      lifetime phase they are present. More likely, the most important gene variants
      for asthma are polymorphisms that exert their influence on the network system
      controlling biological responses to asthma-related exposures.

PMID- 17202287
TI  - Computational approaches to phenotyping: high-throughput phenomics.
AB  - The recent completion of the Human Genome Project has made possible a high
      throughput "systems approach" for accelerating the elucidation of molecular
      underpinnings of human diseases, and subsequent derivation of molecular-based
      strategies to more effectively prevent, diagnose, and treat these diseases.
      Although altered phenotypes are among the most reliable manifestations of altered
      gene functions, research using systematic analysis of phenotype relationships to
      study human biology is still in its infancy. This article focuses on the emerging
      field of high-throughput phenotyping (HTP) phenomics research, which aims to
      capitalize on novel high-throughput computation and informatics technology
      developments to derive genomewide molecular networks of genotype-phenotype
      associations, or "phenomic associations." The HTP phenomics research field faces
      the challenge of technological research and development to generate novel tools
      in computation and informatics that will allow researchers to amass, access,
      integrate, organize, and manage phenotypic databases across species and enable
      genomewide analysis to associate phenotypic information with genomic data at
      different scales of biology. Key state-of-the-art technological advancements
      critical for HTP phenomics research are covered in this review. In particular, we
      highlight the power of computational approaches to conduct large-scale phenomics
      studies.

PMID- 17202289
TI  - Gene expression profiling in human asthma.
AB  - Asthma is a chronic inflammatory disease of the lungs, characterized by airway
      hyperreactivity, mucus hypersecretion, and airflow obstruction. Despite recent
      advances, the genetic regulation of asthma pathogenesis is still largely unknown.
      Gene expression profiling techniques are well suited to study complex diseases
      and hold substantial promise for identifying novel genes and pathways in asthma;
      however, relatively few studies have been completed in human asthma. The few
      studies that have been done have identified many novel candidate genes and
      pathways in asthma pathogenesis, including ALOX15 and serine proteinase
      inhibitors cathepsin C and G. The interpretation of results of these studies
      should be cautious, as limitations include small sample sizes and heterogeneity
      of study populations and tissues sampled. In the future, the promise of gene
      expression studies would be enhanced by the use of larger sample sizes and
      attempts to standardize phenotype, sample collection techniques, and analysis. As
      the field of expression profiling in asthma advances, we hope it will improve our
      understanding of critical questions about mechanisms involved in susceptibility
      to the disease, as well as help to personalize care by improving appropriate
      selection of patients for prevention and treatment strategies.

PMID- 17202290
TI  - Human and murine obliterative bronchiolitis in transplant.
AB  - Obliterative bronchiolitis is a devastating illness that limits the long-term
      success of lung transplantation. Its high prevalence and overall poor response to
      current therapeutic measures demands further research to elucidate pathogenic
      mechanisms. Toward this goal, there is a role for animal models to study the
      mechanisms of obliterative bronchiolitis, such as the murine heterotopic tracheal
      allograft model. This review compares the tracheal allograft model to human
      obliterative bronchiolitis pathology and highlights the important mechanisms of
      airway rejection described using this model. Although certain limitations exist,
      the pursuit of proof-of-concept studies in this model, as well as other animal
      models, can provide the basis for genetic and cellular translational human
      studies directed toward post-transplant obliterative bronchiolitis pathogenesis.
      To meet these challenges, we call for the establishment of a National Institutes
      of Health-supported Lung Transplant Network to better orchestrate translational
      research efforts in obliterative bronchiolitis pathogenesis and treatment, and to
      advance the field of lung transplantation.

PMID- 17202292
TI  - Strategies for identifying modifier genes in cystic fibrosis.
AB  - Even in patients with cystic fibrosis (CF) with identical CFTR genotypes, there
      is a wide range in the severity of lung disease, with some individuals facing
      death or lung transplantation early in life and others demonstrating mild lung
      disease well into adulthood. Although numerous environmental factors have been
      identified that influence CF pulmonary phenotype, there is now growing evidence
      that polymorphic variants in genes besides CFTR play an important role in
      determining severity of CF lung disease. This article reviews the most recent
      findings regarding genetic modifiers in CF and also discusses in detail the
      strategies currently being used to identify novel modifiers of CF pulmonary
      phenotype. These include single- and multicenter studies, twin and sib studies,
      microarray approaches, and whole genome association studies.

PMID- 17202291
TI  - Novel insights into lung transplant rejection by microarray analysis.
AB  - Gene expression microarrays can estimate the prevalence of mRNA for thousands of
      genes in a small sample of cells or tissue. Organ transplant researchers are
      increasingly using microarrays to identify specific patterns of gene expression
      that predict and characterize acute and chronic rejection, and to improve our
      understanding of the mechanisms underlying organ allograft dysfunction. We used
      microarrays to assess gene expression in bronchoalveolar lavage cell samples from
      lung transplant recipients with and without acute rejection on simultaneous lung
      biopsies. These studies showed increased expression during acute rejection of
      genes involved in inflammation, apoptosis, and T-cell activation and
      proliferation. We also studied gene expression during the evolution of airway
      obliteration in a murine heterotopic tracheal transplant model of chronic
      rejection. These studies demonstrated specific patterns of gene expression at
      defined time points after transplantation in allografts, whereas gene expression
      in isografts reverted back to that of native tracheas within 2 wk after
      transplantation. These studies demonstrate the potential power of microarrays to
      identify biomarkers of acute and chronic lung rejection. The application of new
      genetic, genomic, and proteomic technologies is in its infancy, and the
      microarray-based studies described here are clearly only the beginning of their
      application to lung transplantation. The massive amount of data generated per
      tissue or cell sample has spawned an outpouring of invention in the
      bioinformatics field, which is developing methodologies to turn data into
      meaningful and reproducible clinical and mechanistic inferences.

PMID- 17202294
TI  - Wading into the genomic pool to unravel acute lung injury genetics.
AB  - Acute lung injury (ALI) is a common and often devastating illness characterized
      by acute hypoxemia, alveolar flooding, and an unacceptably high morbidity and
      mortality. Because only a fraction of the patients exposed to ALI-inciting events
      progress to development of the syndrome, there is significant interest in the
      identification of genetic factors potentially contributing to ALI susceptibility
      or prognosis. Two complementary strategies used to elucidate ALI genetics
      formulate the "candidate gene approach," whereby genes are identified by either
      global gene expression profiling in humans or animal models of ALI, often
      yielding highly conserved candidates across multiple species, or by related
      literature searches. Relevant variants or single nucleotide polymorphisms (single
      base pair substitutions) in these ALI candidate genes are tested for differences
      in allelic frequency for both ALI susceptibility and outcome between ALI cases
      and control patients at risk for ALI. This approach has yielded important
      variants in a number of genes (angiotensin converting enzyme, surfactant protein
      B, heat shock protein 70, pre-B-cell colony enhancing factor, myosin light chain
      kinase, and macrophage migration inhibitory factor) contributing toward an ALI
      phenotype. An alternative strategy not yet used in ALI genetic studies includes
      genomewide analyses to locate "hot" genomic segments harboring several hundred
      genes, with potential ALI candidate genes embedded within these segments.
      Overall, the detailing of specific ALI-associated polymorphisms will continue to
      provide new insights in the understanding of ALI pathogenesis, reveal novel
      molecular targets, and promote the development of individualized therapies to
      reduce morbidity and mortality from this devastating disease.

PMID- 17202293
TI  - African Americans with asthma: genetic insights.
AB  - It has been well established that genetic factors strongly affect susceptibility
      to asthma and its associated traits. It is less clear to what extent genetic
      variation contributes to the ethnic disparities observed for asthma morbidity and
      mortality. Individuals of African descent with asthma have more severe asthma,
      higher IgE levels, a higher degree of steroid dependency, and more severe
      clinical symptoms than individuals of European descent with asthma but relatively
      few studies have focused on this particularly vulnerable ethnic group. Similar
      underrepresentation exists for other minorities, including Hispanics. In this
      review, a summary of linkage and association studies in populations of African
      descent is presented, and the role of linkage disequilibrium in the dissection of
      a complex trait such as asthma is discussed. Consideration for the impact of
      population stratification in recently admixed populations (i.e., European,
      African) is essential in genetic association studies focusing on African ancestry
      groups. With the most recent update on the International HapMap Project,
      efficient selection of haplotype tagging single nucleotide polymorphisms (htSNPs)
      for African Americans has accelerated and efficiency of htSNPs chosen from one
      population to represent other continental groups (e.g., African) has been
      demonstrated. Cutting-edge approaches, such as genomewide association studies,
      admixture mapping, and phylogenetic analyses, offer new opportunities for
      dissecting the genetic basis for asthma in populations of African descent.

PMID- 17202295
TI  - Microarray-based analysis of ventilator-induced lung injury.
AB  - Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are a
      frequent cause of intensive care unit admission, affecting over 200,000 patients
      in the United States each year. Mechanical ventilation is a life-saving
      intervention in the setting of ARDS and ALI, but clinical trials have
      demonstrated that mechanical ventilation with excessive tidal volumes plays a
      role in promoting and perpetuating lung injury and leads to excess mortality.
      This process has been labeled ventilator-induced lung injury (VILI), but the
      molecular mechanisms driving this process and its interactions with predisposing
      risk factors such as sepsis and chemical injury remain incompletely understood.
      Genome-wide measurements of gene expression using microarray technology represent
      a powerful tool to examine the pathophysiology of VILI. Several recent studies
      have used this approach to study VILI in isolation and associated with endotoxin
      instillation or saline lavage. These studies and others examining gene expression
      profiles in epithelial cells subjected to cyclic stretch have provided novel
      insights on the molecular mechanisms underlying VILI. This review will summarize
      these findings and discuss implications for future studies.

PMID- 17202296
TI  - Towards systems biology of human pulmonary fibrosis.
AB  - The integrated effect of multiple pathways, molecules, genetic polymorphisms,
      environmental stimuli, and possible infection determines the lung phenotype in
      idiopathic pulmonary fibrosis (IPF), a chronic progressive and often lethal lung
      disease. Systems biology approaches aim to provide a systemwide view of
      biological process using computational tools and high-throughput technologies.
      Although much of the analysis of genome-level transcriptional high-resolution
      profiles of IPF was reductionist, usually focusing on a single factor in the
      disease process, there are some studies that implement systems approaches. We
      discuss these analyses and provide examples of the global analysis of IPF,
      hypersensitivity pneumonitis, and nonspecific interstitial pneumonia. Detailed
      quantitative phenotyping and correlation with microarray results as well as high
      throughput genotyping should provide us with the datasets to implement systems
      biology approaches in fibrosis research. Interdisciplinary teams and training of
      junior investigators in the vocabulary of systems biology should allow us to use
      these datasets integratively and generate a global model of human pulmonary
      fibrosis.

PMID- 17202297
TI  - Using mouse genomics to understand idiopathic interstitial fibrosis.
AB  - Idiopathic interstitial pneumonia represents a broad category of lung disorders
      characterized by scarring or fibrosis of the lung accompanied by varying degrees
      of inflammation. A number of important hypotheses based on clinical observations
      have substantially contributed to our understanding of the pathogenesis of the
      most insidious and devastating of the idiopathic interstitial pneumonias,
      idiopathic interstitial fibrosis (IIF). Patients with IIF usually present late in
      the course of their illness; thus, animal models of the early, preclinical stage
      of these diseases are needed. Although no model faithfully recapitulates the
      clinical course of disease or the histopathology observed in humans, all result
      in scarring of the lung and may therefore be used to understand the biological
      processes that contribute to this scarring. The purpose of this article is to
      summarize the application of mouse genetic and genomic tools to these models to
      advance our understanding of IIF and to describe emerging agnostic approaches to
      identifying genes important to the fibroproliferative component of IIF.

PMID- 17202298
TI  - Expression profiling in granulomatous lung disease.
AB  - Granulomatous lung diseases, such as sarcoidosis, hypersensitivity pneumonitis,
      Wegener's granulomatosis, and chronic beryllium disease, along with granulomatous
      diseases of known infectious etiologies, such as tuberculosis, are major causes
      of morbidity and mortality throughout the world. Clinical manifestations of these
      diseases are highly heterogeneous, and the determinants of disease susceptibility
      and clinical course (e.g., resolution vs. chronic, progressive fibrosis) are
      largely unknown. The underlying pathogenic mechanisms of these diseases also
      remain poorly understood. Within this context, these diseases have been
      approached using genomic and proteomic technologies to allow us to identify
      patterns of gene/protein expression that track with clinical disease or to
      identify new pathways involved in disease pathogenesis. The results from these
      initial studies highlight the potential for these "-omics" approaches to reveal
      novel insights into the pathogenesis of granulomatous lung disease and provide
      new tools to improve diagnosis, clinical classification, course prediction, and
      response to therapy. Realizing this potential will require collaboration among
      multidisciplinary groups with expertise in the respective technologies,
      bioinformatics, and clinical medicine for these complex diseases.

PMID- 17202301
TI  - Genomics of sleep-disordered breathing.
AB  - The technologies of genomics and proteomics are powerful tools for discovering
      novel gene and protein expression responses to disease. Considerable evidence
      indicates that a genetic basis exists to the causes of sleep-disordered
      breathing, in particular its most common form of obstructive sleep apnea (OSA),
      which is characterized by periods of intermittent hypoxia and disrupted sleep.
      However, the genetic contribution to the pathogenesis of OSA has largely been
      determined using traditional genetic approaches of family, twin, and linkage
      studies in clinical populations and quantitative trait loci and targeted gene
      procedures in animal models of OSA. In contrast to the pathogenesis of OSA, the
      consequences or sequelae of OSA are highly amenable to genomic and proteomic
      approaches. Animal studies have assessed changes in gene and protein expression
      in multiple organ systems in response to intermittent hypoxia and sleep
      deprivation and uncovered novel gene activation paradigms. The first tentative
      steps have been made toward applying proteomic analyses of blood and urine from
      patients with OSA as a potential screening tool for diagnosis in the clinical
      setting. It is anticipated that genomic and proteomic technologies will become
      increasingly used in the area of OSA with the unprecedented access to tissue in
      procedures such as bariatric surgery. OSA represents a severe insult to the
      oxygenation of tissues and the homeostasis of sleep, and genomic and proteomic
      approaches hold promise for defining previously unexplored mechanisms and
      pathways that lead to downstream pathologies, including hypertension, insulin
      resistance, and neurocognitive dysfunction.

PMID- 17202300
TI  - Gene expression profiling in pulmonary hypertension.
AB  - The application of functional genomics toward the investigation of complex
      medical conditions has moved from a futuristic dream to a medical reality in less
      then a decade. The ability to examine the expression level of thousands of genes
      simultaneously has opened the door for entirely new approaches toward
      experimental observation and discovery. The resulting data from these genomic
      studies is being collected at an unprecedented scale. This wealth of data can
      present its own obstacles in terms of analysis. However, as new and more powerful
      means of examining these experiments are developed, medical science is reaping
      significant benefit. The power of microarray gene expression analysis has been
      directed at a diverse and complex array of diseases. As will be discussed in this
      article, the investigation of pulmonary hypertension has already benefited
      greatly from the application of this technology.

PMID- 17202299
TI  - Genetics of sarcoidosis: candidate genes and genome scans.
AB  - Human leukocyte antigen class II allele associations and T-cell receptor beta
      chain bias in sarcoidosis suggest a specific disease-triggering antigen exposure
      in a genetically susceptible host. The cause of sarcoidosis has been elusive, but
      genetics provides one of the few promising avenues to further our understanding.
      We review the association studies and genome scans used to identify the genes
      involved in sarcoidosis.

PMID- 17202302
TI  - Expression profiling and lung cancer development.
AB  - Recent lung cancer research has been directed to using molecular approaches to
      facilitate early diagnosis, to identify clinically relevant biological factors
      associated with histologic heterogeneity, and to identify novel therapeutic
      agents. This research takes advantage of technical advances that allow rapid high
      throughput assays to interrogate the genome, proteome, and epigenome. In this
      review of gene expression profiling in lung carcinogenesis, we will focus upon
      recent advances in the understanding of malignant transformation of lung
      epithelial cells and of lung cancer differentiation and progression. These
      studies have provided important information about the genomic alterations of
      tobacco smoke-associated airway field carcinogenesis and about the developmental
      pathways that mediate lung tumor invasion and histologic differentiation in
      response to injury.

PMID- 17202303
TI  - Impact of spiramycin treatment and gestational age on maturation of Toxoplasma
      gondii immunoglobulin G avidity in pregnant women.
AB  - The objective of the present study was to investigate the maturation of
      immunoglobulin G (IgG) avidity after Toxoplasma gondii seroconversion during
      pregnancy and the factors that affect IgG avidity over time. The study used 309
      serum samples from 117 women and a multiple linear mixed regression analysis to
      show the patterns of variation of IgG avidity throughout gestation. The IgG
      avidity ratios and the patterns of their evolution with time were quite diverse
      among the women and were statistically heterogeneous (P = 0.011); however, the
      trend was toward a statistically significant increase (P < 0.0001). On average, a
      1.0167-fold increase was observed for each additional gestational week after the
      putative date of infection. At 12 weeks after putative infection (the expected
      IgG avidity maturation time), the mean avidity ratio was 16.6% (95% confidence
      interval, 15.4 to 17.9%). At all times, the avidity ratio remained significantly
      heterogeneous among the women (P < 0.05); for 95% of them, that ratio ranged from
      7.8 to 35.3% at 12 weeks after putative infection. Maternal age at the putative
      time of infection did not influence the maturation of IgG avidity. However, on
      average, a 1.009-fold decrease (P = 0.03) in that avidity was observed for each
      additional week of gestational age before infection and a 1.03-fold increase (P =
      0.0003) was observed for each additional week of delay to the onset of spiramycin
      treatment. The rate of increase in the avidity ratio was lower if infection
      occurred late in pregnancy and higher if the delay to treatment was long. This
      information cannot allow accurate determination of the delay since the time of
      infection. The present results provide support for interpretation of the assay
      and caution against overinterpretation.

PMID- 17202305
TI  - Use of MAG1 recombinant antigen for diagnosis of Toxoplasma gondii infection in
      humans.
AB  - This paper describes the cloning, purification, and serological applications of
      matrix antigen MAG1 of Toxoplasma gondii. The expression system used allows the
      production of a large amount of T. gondii recombinant protein, which was assessed
      for its potential use in an enzyme-linked immunosorbent assay (ELISA) for
      detection of T. gondii infection in humans. Serum samples from 117 patients with
      different stages of infection, along with 10 serum samples from seronegative
      patients obtained for routine diagnostic tests, were used. The results were
      compared with those of an ELISA that uses a native T. gondii antigen extract. The
      MAG1 antigen detected antibodies more frequently from the acute stage (97.3%)
      than from the chronic stage (7.5%) of toxoplasmosis. Hence, this antigen may be
      used as a tool for detection of T. gondii immunoglobulin G antibodies in persons
      with acute toxoplasmosis.

PMID- 17202307
TI  - Protective effect of human heat shock protein 60 suggested by its association
      with decreased seropositivity to pathogens.
AB  - The presence of heat shock protein 60 (Hsp60) in human plasma has been linked
      with cardiovascular disease (CVD). In this study, the examination of the
      relationship between Hsp60 in plasma and seropositivity for three microbial
      agents, which are thought to be risk factors for CVD, surprisingly revealed a
      negative association between Hsp60 and seropositivity, suggesting a protective
      effect of this circulating stress protein.

PMID- 17202304
TI  - Effects of a diphtheria-tetanus-acellular pertussis vaccine on immune responses
      in murine local lymph node and lung allergy models.
AB  - We have previously shown that in mice, diphtheria-tetanus-acellular pertussis
      (DTaP) vaccination before Bordetella pertussis infection resulted in, besides
      effective clearance, immediate hypersensitivity (lung eosinophilia, increased
      total serum immunoglobulin E [IgE], and increased ex vivo Th2 cytokine production
      by cells from the bronchial lymph nodes). To better appreciate the extent of
      these findings, we measured DTaP vaccination effects in the local lymph node
      assay (LLNA) and an ovalbumin (OVA) lung allergy model. In the LLNA, mice were
      vaccinated or adjuvant treated before being sensitized with trimellitic anhydride
      (TMA; inducing a Th2-directed response) and dinitrochlorobenzene (DNCB; inducing
      a Th1-directed response). Compared to the adjuvant-treated controls, the
      vaccinated mice showed a decreased response to TMA and (to a much lesser extent)
      an increased response to DNCB. The decreased response to TMA coincided with
      increased transforming growth factor beta levels. With the exception of
      filamentous hemagglutinin, all vaccine constituents contributed to the decreased
      response to TMA. In the lung allergy model, sensitization induced OVA-specific
      IgE, lung pathology (peribronchiolitis, perivasculitis, and hypertrophy of the
      bronchiolar mucus cells) and increased the number of eosinophils, lymphocytes,
      and neutrophils in the bronchoalveolar lavage fluid. Vaccination failed to
      modulate these parameters. In conclusion, although DTaP vaccination may affect
      the LLNA response, we found no evidence of an effect on lung allergy.

PMID- 17202306
TI  - Intranasal coadministration of live lactococci producing interleukin-12 and a
      major cow's milk allergen inhibits allergic reaction in mice.
AB  - The Th1/Th2 balance deregulation toward a Th2 immune response plays a central
      role in allergy. We previously demonstrated that administration of recombinant
      Lactococcus lactis strains expressing bovine beta-lactoglobulin (BLG), a major
      cow's milk allergen, partially prevents mice from sensitization. In the present
      study, we aimed to improve this preventive effect by coadministration of L.
      lactis BLG and a second recombinant L. lactis strain producing biologically
      active interleukin-12 (IL-12). This L. lactis strain producing IL-12 was
      previously used to enhance the Th1 immune response in a tumoral murine model (L.
      G. Bermudez-Humaran et al., J. Immunol. 175:7297-7302, 2005). A comparison of the
      administration of either BLG alone or BLG in the presence of IL-12 was conducted.
      A BLG-specific primary Th1 immune response was observed only after intranasal
      coadministration of both L. lactis BLG and IL-12-producing L. lactis, as
      demonstrated by the induction of serum-specific immunoglobulin G2a (IgG2a)
      concomitant with gamma interferon secretion by splenocytes, confirming the
      adjuvanticity of IL-12-producing L. lactis. Immunized mice were further
      sensitized by intraperitoneal administration of purified BLG, and the allergic
      reaction was elicited by intranasal challenge with purified BLG. Mice pretreated
      with BLG in either the presence or the absence of IL-12 were rendered completely
      tolerant to further allergic sensitization and elicitation. Pretreatment with
      either L. lactis BLG or L. lactis BLG and IL-12-producing L. lactis induces
      specific anti-BLG IgG2a production in serum and bronchoalveolar lavage (BAL)
      fluid. Although specific serum IgE was not affected by these pretreatments, the
      levels of eosinophilia and IL-5 secretion in BAL fluid were significantly reduced
      after BLG challenge in the groups pretreated with L. lactis BLG and L. lactis BLG
      IL-12-producing L. lactis, demonstrating a decreased allergic reaction. Our data
      demonstrate for the first time (i) the induction of a protective Th1 response by
      the association of L. lactis BLG and IL-12-producing L. lactis which inhibits the
      elicitation of the allergic reaction to BLG in mice and (ii) the efficiency of
      intranasal administration of BLG for the induction of tolerance.

PMID- 17202308
TI  - Association between mannose-binding lectin deficiency and septic shock following
      acute pyelonephritis due to Escherichia coli.
AB  - Structural and promoter MBL2 gene polymorphisms responsible for low MBL levels
      are associated with increased risk of infection. The objective of this study was
      to assess the possible association between polymorphisms of the MBL2 gene and the
      incidence of septic shock and bacteremia in patients with acute pyelonephritis
      due to Escherichia coli. The study included 62 female patients with acute
      pyelonephritis due to E. coli who required hospital admission, as well as 133
      healthy control subjects. Six single-nucleotide polymorphisms (-550 G/C, -221
      C/G, +4 C/T, codon 52 CGT/TGT, codon 54 GGC/GAC, and codon 57 GGA/GAA) in the
      MBL2 gene were genotyped by using a sequence-based typing technique. No
      significant differences were observed in the frequencies for low-expression MBL2
      genotypes (O/O and LXA/O) between patients with acute pyelonephritis and healthy
      controls. Patients with acute pyelonephritis and septic shock had a higher
      incidence of low-expression MBL2 genotypes than patients with acute
      pyelonephritis without septic shock (odds ratio = 9.019, 95% confidence interval
      = 1.23 to 65.93; P = 0.03). No association was found between bacteremic acute
      pyelonephritis and low-expression MBL2 genotypes. We found that low-expression
      MBL2 genotypes predispose to septic shock but not to bacteremia in patients with
      E. coli-induced acute pyelonephritis. Determination of MBL2 polymorphisms could
      be useful for assessing the risk of septic shock in women undergoing acute
      pyelonephritis.

PMID- 17202309
TI  - Antigenic divergence between Bordetella pertussis clinical isolates from Moscow,
      Russia, and vaccine strains.
AB  - We analyzed temporal changes in the frequencies of the ptxA, prn, fim2, and fim3
      alleles in Bordetella pertussis strains isolated from pertussis patients in
      Moscow, Russia, from 1948 to 2004. The three strains used for the whole-cell
      vaccine harbored the alleles ptxA2, ptxA4, prn1, fim2-1, and fim3A. Vaccine-type
      alleles of ptxA (ptxA2 and ptxA4) were characteristic for all prevaccination
      strains and for 96% of the strains isolated in the 1960s and 1970s. At the
      beginning of the 1970s, ptxA2 and ptxA4 were replaced by the ptxA1 allele. In the
      1980s and to the present, strains with ptxA1 were predominant in the B. pertussis
      population. All prevaccination strains harbored the prn1 allele, which
      corresponds to the vaccine-type allele. In subsequent years, the proportion of
      strains with the prn1 allele decreased and the proportion of prn3 and prn2
      strains increased. From 2002 to 2004 strains with prn2 or prn3 were predominant
      in the B. pertussis population. The vaccine-type alleles fim2-1 and fim3A were
      found in all prevaccination strains and in 92% of the strains isolated from 1960
      to 1989. The fim2-2 and fim3B alleles were first observed at the beginning of the
      1980s. In subsequent years, these strains became predominant. Together with
      waning immunity, the antigenic divergence between vaccine strains and clinical
      isolates observed in the Moscow area may explain the persistence of pertussis,
      despite the high rates of vaccine coverage. The results demonstrate that the
      selection of B. pertussis strains for vaccine manufacturing must be based on a
      thorough study of the B. pertussis population.

PMID- 17202310
TI  - Recombinant truncated nucleocapsid protein as antigen in a novel immunoglobulin M
      capture enzyme-linked immunosorbent assay for diagnosis of severe acute
      respiratory syndrome coronavirus infection.
AB  - We report the development of an immunoglobulin M (IgM) antibody capture enzyme
      linked immunosorbent assay (MAC-ELISA) for severe acute respiratory syndrome
      coronavirus (SARS-CoV) by using recombinant truncated SARS-CoV nucleocapsid
      protein as the antigen. The newly developed MAC-ELISA had a specificity and
      sensitivity of 100% as evaluated by using sera from healthy volunteers and
      patients with laboratory-confirmed SARS. Using serial serum samples collected
      from SARS patients, the times to seroconversion were determined by IgM antibody
      detection after SARS-CoV infection. The median time to seroconversion detection
      was 8 days (range, 5 to 17 days) after disease onset, and the seroconversion
      rates after the onset of illness were 33% by the first week, 97% by the second
      week, and 100% by the third week. Compared with the results of our previous
      report on the detection of IgG, the median seroconversion time by IgM detection
      was 3 days earlier and the seroconversion rate by the second week after the
      illness for IgM was significantly higher than by IgG assay. Our results
      indicating that the IgM response appears earlier than IgG after SARS-CoV
      infection in consistent with those for other pathogens. Our newly developed MAC
      ELISA system offers a new alternative for the confirmation of SARS-CoV infection.

PMID- 17202311
TI  - Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese
      women.
AB  - PURPOSE: Somatic mutations of PIK3CA, which encodes the p110alpha catalytic
      subunit of phosphatidylinositol 3-kinase, have recently been shown to play an
      important role in the pathogenesis and progression of human breast cancers. In
      this study, the frequency of PIK3CA mutations and their relationship with
      clinicopathologic and biological variables were investigated in Japanese breast
      cancers. EXPERIMENTAL DESIGN: Mutational analysis of PIK3CA was done in 188
      primary breast cancers of Japanese women. Relationship of these mutations with
      various clinicopathologic variables [histologic type, tumor size, histologic
      grade, lymph node status, estrogen receptor (ER)-alpha and progesterone receptor
      status, and prognosis], biological variables [phospho-AKT (pAKT) and HER2
      expression determined by immunohistochemistry], and p53 mutation status was
      studied. RESULTS: Missense mutations of PIK3CA were found in 44 of 158 invasive
      ductal carcinomas, 4 of 10 invasive lobular carcinomas, 1 of 4 mucinous
      carcinomas, 2 of 2 squamous carcinomas, and 2 of 2 apocrine carcinomas, but no
      mutation was found in 12 noninvasive ductal carcinomas. PIK3CA-mutated tumors
      were found to be more likely to be ER-alpha positive (P < 0.05) and pAKT positive
      (P < 0.05). There was no significant association between PIK3CA mutations and p53
      mutation status. PIK3CA mutations were significantly (P < 0.05) associated with a
      favorable prognosis, and multivariate analysis showed that PIK3CA mutation status
      was a significant (P < 0.05) prognostic factor independent of the other
      conventional prognostic factors. CONCLUSIONS: The frequency of PIK3CA mutations
      in Japanese breast cancers is similar to that of Caucasian breast cancers.
      Association of PIK3CA mutations with positive pAKT and positive ER-alpha suggests
      that PIK3CA mutations might exert their effects through activation of the
      phosphatidylinositol 3-kinase/AKT/ER-alpha pathway. PIK3CA mutations seem to have
      a potential to be used as an indicator of favorable prognosis.

PMID- 17202312
TI  - Microarray-based identification of tenascin C and tenascin XB, genes possibly
      involved in tumorigenesis associated with neurofibromatosis type 1.
AB  - PURPOSE: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a
      complex variety of clinical manifestations. The hallmark of NF1 is the onset of
      heterogeneous (dermal or plexiform) benign neurofibromas. Plexiform neurofibromas
      can give rise to malignant peripheral nerve sheath tumors, which are resistant to
      conventional therapies. EXPERIMENTAL DESIGN: To identify new signaling pathways
      involved in the malignant transformation of plexiform neurofibromas, we applied a
      22,000-oligonucleotide microarray approach to a series of plexiform neurofibromas
      and malignant peripheral nerve sheath tumors. Changes in the expression of
      selected genes were then confirmed by real-time quantitative reverse
      transcription-PCR. RESULTS: We identified two tenascin gene family members that
      were significantly deregulated in both human NF1-associated tumors and NF1
      deficient primary cells: Tenascin C (TNC) was up-regulated whereas tenascin XB
      (TNXB) was down-regulated during tumor progression. TNC activation is mainly due
      to the up-regulation of large TNC splice variants. Immunohistochemical studies
      showed that TNC transcripts are translated into TNC protein in TNC-overexpressing
      tumors. Aberrant transcriptional activation of TNC seems to be principally
      mediated by activator protein transcription factor complexes. CONCLUSION: TNXB
      and TNC may be involved in the malignant transformation of plexiform
      neurofibromas. Anti-TNC antibodies, already used successfully in clinical trials
      to treat malignant human gliomas, may be an appropriate new therapeutic strategy
      for NF1.

PMID- 17202313
TI  - HLA mismatching within or outside of cross-reactive groups (CREGs) is associated
      with similar outcomes after unrelated hematopoietic stem cell transplantation.
AB  - The National Marrow Donor Program maintains a registry of volunteer donors for
      patients in need of a hematopoietic stem cell transplantation. Strategies for
      selecting a partially HLA-mismatched donor vary when a full match cannot be
      identified. Some transplantation centers limit the selection of mismatched donors
      to those sharing mismatched antigens within HLA-A and HLA-B cross-reactive groups
      (CREGs). To assess whether an HLA mismatch within a CREG group ("minor") may
      result in better outcome than a mismatch outside CREG groups ("major"), we
      analyzed validated outcomes data from 2709 bone marrow and peripheral blood stem
      cell transplantations. Three-hundred and ninety-six pairs (15%) were HLA-DRB1
      allele matched but had an antigen-level mismatch at HLA-A or HLA-B. Univariate
      and multivariate analyses of engraftment, graft-versus-host disease, and survival
      showed that outcome is not significantly different between minor and major
      mismatches (P = .47, from the log-rank test for Kaplan-Meier survival). However,
      HLA-A, HLA-B, and HLA-DRB1 allele-matched cases had significantly better outcome
      than mismatched cases (P < .001). For patients without an HLA match, the
      selection of a CREG-compatible donor as tested does not improve outcome.

PMID- 17202314
TI  - Flt3 is dispensable to the Hoxa9/Meis1 leukemogenic cooperation.
AB  - HOX genes, MEIS1, and FLT3 are frequently up-regulated in human myeloid
      leukemias. Meis1 cooperates with Hox genes to induce leukemias in mice,
      hypothetically the consequence of Meis1-induced Flt3 overexpression. To test
      this, we compared the properties of Flt3(-/-) and Flt3(+/+) progenitors
      transduced with Hoxa9 or Hoxa9/Meis1. In a myeloid clonogenic assay, Meis1
      greatly enhanced the proliferation of Hoxa9-expressing cells, massively up
      regulating Flt3 protein. However, the transforming potential of Hoxa9/Meis1 was
      unaltered in Flt3(-/-) cells. All mice that received Hoxa9/Meis1-transduced
      progenitors succumbed to rapid acute myeloid leukemias regardless of Flt3
      genotype. Flt3 expression levels in leukemic blasts did not correlate with
      parameters reflecting their proliferative rate or their impaired differentiation.
      Furthermore, analysis of c-Myb expression levels in Hoxa9/Meis1-transformed cells
      showed that the up-regulation of this critical downstream effector was
      independent of Flt3. Altogether, our findings demonstrate that Flt3 is
      dispensable to the oncogenic cooperation of Meis1 with Hoxa9.

PMID- 17202315
TI  - Tumor suppressor PTEN is a physiologic suppressor of chemoattractant-mediated
      neutrophil functions.
AB  - The recruitment and activation of neutrophils at infected tissues is essential
      for host defense against invading microorganisms. However, excessive neutrophil
      recruitment or activation can also damage the surrounding tissues and cause
      unwanted inflammation. Hence, the responsiveness of neutrophils needs to be
      tightly regulated. In this study, we have investigated the functional role of
      tumor suppressor PTEN in neutrophils by using a mouse line in which PTEN is
      disrupted only in myeloid-derived cells. Chemoattractant-stimulated PTEN(-/-)
      neutrophils displayed significantly higher Akt phosphorylation and actin
      polymerization. A larger fraction of these neutrophils displayed membrane ruffles
      in response to chemoattractant stimulation. In addition, chemoattractant-induced
      transwell migration and superoxide production were also augmented. Single-cell
      chemotaxis assays showed that PTEN(-/-) neutrophils have a small (yet
      statistically significant) defect in directionality. However, these neutrophils
      also showed an increase in cell speed. As a result, overall chemotaxis, which
      depends on speed and directionality, was not affected. Consistent with the
      increased responsiveness of PTEN(-/-) neutrophils, the in vivo recruitment of
      these cells to the inflamed peritoneal cavity was significantly enhanced. Thus,
      as a physiologic-negative regulator, PTEN should be a promising therapeutic
      target for modulating neutrophil functions in various infectious and inflammatory
      diseases.

PMID- 17202316
TI  - The role of chemerin in the colocalization of NK and dendritic cell subsets into
      inflamed tissues.
AB  - Chemerin is a chemotactic agonist recently identified as the ligand of ChemR23, a
      serpentine receptor expressed by mononuclear phagocytes and dendritic cells
      (DCs). This study shows that blood CD56(low)CD16(+) natural killer (NK) cells
      selectively express functional ChemR23 and that this receptor is coexpressed with
      CXCR1, the CXCL8 receptor, and the KIR receptors. In vitro culturing of NK cells
      with IL-2 or IL-15 induced a delayed and time-dependent down-regulation of
      ChemR23 that was associated with the inhibition of NK cell migration to chemerin.
      Biopsies obtained from patients with oral lichen planus presented an infiltration
      of CD94(+)CD3(-)CD56(+) NK cells that coexpressed ChemR23. The same biopsies were
      infiltrated by myeloid, DC-SIGN(+) and plasmacytoid, CD123(+)BDCA2(+), ChemR23(+)
      dendritic cells that were occasionally associated with NK cells. In the same
      histologic sections, chemerin was expressed by inflamed dermal endothelium. These
      findings propose a role for the ChemR23/chemerin axis in the recruitment of blood
      NK cells and strongly implicate chemerin as a key factor for the colocalization
      of NK cells and DC subsets in pathologic peripheral tissues.

PMID- 17202318
TI  - Effective graft depletion of MiHAg T-cell specificities and consequences for
      graft-versus-host disease.
AB  - Minor histocompatibility antigen (MiHAg) differences between donor and recipient
      in MHC-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      often result in graft-versus-host disease (GVHD). While MiHAg-specific T-cell
      responses can in theory be directed against a large number of polymorphic
      differences between donor and recipient, in practice, T-cell responses against
      only a small set of MiHAgs appear to dominate the immune response, and it has
      been suggested that immunodominance may predict an important contribution to the
      development of GVHD. Here, we addressed the feasibility of graft engineering by
      ex vivo removal of T cells with 1 or more defined antigen specificities in a well
      characterized experimental HSCT model (B6 --> BALB.B). We demonstrate that
      immunodominant H60- and H4-specific CD8(+) T-cell responses can be effectively
      suppressed through MHC class I tetramer-mediated purging of the naive CD8(+) T
      cell repertoire. Importantly, the development of GVHD occurs unimpeded upon
      suppression of the immunodominant MiHAg-specific T-cell response. These data
      indicate that antigen-specific graft engineering is feasible, but that parameters
      other than immunodominance may be required to select T-cell specificities that
      are targeted for removal.

PMID- 17202317
TI  - B cells and T cells are critical for the preservation of bone homeostasis and
      attainment of peak bone mass in vivo.
AB  - Bone homeostasis is regulated by a delicate balance between osteoblastic bone
      formation and osteoclastic bone resorption. Osteoclastogenesis is controlled by
      the ratio of receptor activator of NF-kappaB ligand (RANKL) relative to its decoy
      receptor, osteoprotegerin (OPG). The source of OPG has historically been
      attributed to osteoblasts (OBs). While activated lymphocytes play established
      roles in pathological bone destruction, no role for lymphocytes in basal bone
      homeostasis in vivo has been described. Using immunomagnetic isolation of bone
      marrow (BM) B cells and B-cell precursor populations and quantitation of their
      OPG production by enzyme-linked immunosorbent assay (ELISA) and real-time reverse
      transcriptase-polymerase chain reaction (RT-PCR), cells of the B lineage were
      found to be responsible for 64% of total BM OPG production, with 45% derived from
      mature B cells. Consistently B-cell knockout (KO) mice were found to be
      osteoporotic and deficient in BM OPG, phenomena rescued by B-cell reconstitution.
      Furthermore, T cells, through CD40 ligand (CD40L) to CD40 costimulation, promote
      OPG production by B cells in vivo. Consequently, T-cell-deficient nude mice, CD40
      KO mice, and CD40L KO mice display osteoporosis and diminished BM OPG production.
      Our data suggest that lymphocytes are essential stabilizers of basal bone
      turnover and critical regulators of peak bone mass in vivo.

PMID- 17202319
TI  - Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of
      chronic myelogenous leukemia cells.
AB  - Imatinib mesylate (Gleevec) is effective therapy against Philadelphia chromosome
      positive leukemia, but resistance develops in all phases of the disease. Bcr/Abl
      point mutations and other alterations reduce the kinase inhibitory activity of
      imatinib mesylate; thus, agents that target Bcr/Abl through unique mechanisms may
      be needed. Here we describe the activity of WP1130, a small molecule that
      specifically and rapidly down-regulates both wild-type and mutant Bcr/Abl protein
      without affecting bcr/abl gene expression in chronic myelogenous leukemia (CML)
      cells. Loss of Bcr/Abl protein correlated with the onset of apoptosis and reduced
      phosphorylation of Bcr/Abl substrates. WP1130 did not affect Hsp90/Hsp70 ratios
      within the cells and did not require the participation of the proteasomal pathway
      for loss of Bcr/Abl protein. WP1130 was more effective in reducing leukemic
      versus normal hematopoietic colony formation and strongly inhibited colony
      formation of cells derived from patients with T315I mutant Bcr/Abl-expressing CML
      in blast crisis. WP1130 suppressed the growth of K562 heterotransplanted tumors
      as well as both wild-type Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells
      transplanted into nude mice. Collectively, our results demonstrate that WP1130
      reduces wild-type and T315I mutant Bcr/Abl protein levels in CML cells through a
      unique mechanism and may be useful in treating CML.

PMID- 17202321
TI  - Reciprocal negative regulation between thyrotropin/3',5'-cyclic adenosine
      monophosphate-mediated proliferation and caveolin-1 expression in human and
      murine thyrocytes.
AB  - The expression of caveolins is down-regulated in tissue samples of human thyroid
      autonomous adenomas and in the animal model of this disease. Because several cell
      types present in thyroid express caveolins, it remained unclear if this down
      regulation occurs in thyrocytes and which are the mechanism and role of this down
      regulation in the tumor context. Here we show that prolonged stimulation of
      isolated human thyrocytes by TSH/cAMP/cAMP-dependent protein kinase inhibits
      caveolins' expression. The expression of caveolins is not down-regulated by
      activators of other signaling pathways relevant to thyroid growth/function.
      Therefore, the down-regulation of caveolins' expression in autonomous adenomas is
      a direct consequence of the chronic activation of the TSH/cAMP pathway in
      thyrocytes. The down-regulation of caveolin-1 occurs at the mRNA level, with a
      consequent protein decrease. TSH/cAMP induces a transcription-dependent,
      translation-independent destabilization of the caveolin-1 mRNA. This effect is
      correlated to the known proliferative role of that cascade in thyrocytes. In
      vivo, thyrocytes of caveolin-1 knockout mice display enhanced proliferation. This
      demonstrates, for the first time, the in vivo significance of the specific
      caveolin-1 down-regulation by one mitogenic cascade and its relation to a human
      disease.

PMID- 17202322
TI  - Arachidonic acid metabolism as a potential mediator of cardiac fibrosis
      associated with inflammation.
AB  - An increase in left ventricular collagen (cardiac fibrosis) is a detrimental
      process that adversely affects heart function. Strong evidence implicates the
      infiltration of inflammatory cells as a critical part of the process resulting in
      cardiac fibrosis. Inflammatory cells are capable of releasing arachidonic acid,
      which may be further metabolized by cyclooxygenase, lipoxygenase, and cytochrome
      P450 monooxygenase enzymes to biologically active products, including PGs,
      leukotrienes, epoxyeicosatrienoic acids, and hydroxyeicosatetraenoic acids. Some
      of these products have profibrotic properties and may represent a pathway by
      which inflammatory cells initiate and mediate the development of cardiac
      fibrosis. In this study, we critically review the current literature on the
      potential link between this pathway and cardiac fibrosis.

PMID- 17202320
TI  - An essential role for IL-17 in preventing pathogen-initiated bone destruction:
      recruitment of neutrophils to inflamed bone requires IL-17 receptor-dependent
      signals.
AB  - IL-17 and its receptor are founding members of a novel family of inflammatory
      cytokines. IL-17 plays a pathogenic role in rheumatoid arthritis (RA)-associated
      bone destruction. However, IL-17 is also an important regulator of host defense
      through granulopoiesis and neutrophil trafficking. Therefore, the role of IL-17
      in pathogen-initiated bone loss was not obvious. The most common form of
      infection-induced bone destruction occurs in periodontal disease (PD). In
      addition to causing significant morbidity, PD is a risk factor for
      atherosclerotic heart disease and chronic obstructive pulmonary disease (COPD).
      Similar to RA, bone destruction in PD is caused by the immune response. However,
      neutrophils provide critical antimicrobial defense against periodontal organisms.
      Since IL-17 is bone destructive in RA but a key regulator of neutrophils, we
      examined its role in inflammatory bone loss induced by the oral pathogen
      Porphyromonas gingivalis in IL-17RA-deficient mice. These mice showed enhanced
      periodontal bone destruction, suggesting a bone-protective role for IL-17,
      reminiscent of a neutrophil deficiency. Although IL-17RA-deficient neutrophils
      functioned normally ex vivo, IL-17RA knock-out (IL-17RA(KO)) mice exhibited
      reduced serum chemokine levels and concomitantly reduced neutrophil migration to
      bone. Consistently, CXCR2(KO) mice were highly susceptible to alveolar bone loss;
      interestingly, these mice also suggested a role for chemokines in maintaining
      normal bone homeostasis. These results indicate a nonredundant role for IL-17 in
      mediating host defense via neutrophil mobilization.

PMID- 17202323
TI  - Cutting Edge: KIR3DS1, a gene implicated in resistance to progression to AIDS,
      encodes a DAP12-associated receptor expressed on NK cells that triggers NK cell
      activation.
AB  - The killer cell Ig-like receptor (KIR) gene, KIR3DS1, has been implicated in
      slowing disease progression in HIV infection; however, little is known about its
      expression, function, or ligand specificity. Using retrovirally transduced NKL
      cells and peripheral blood NK cells from KIR3DS1-positive donors we assessed
      expression of this gene by flow cytometry and its function by in vitro assays
      measuring KIR3DS1-induced cell-mediated cytotoxicity and cytokine production. In
      the present study, we demonstrate that KIR3DS1 is expressed on peripheral blood
      NK cells and triggers both cytotoxicity and IFN-gamma production. Using
      cotransfection and coimmunoprecipitation, we found that KIR3DS1 associates with
      the ITAM-bearing adaptor, DAP12. Soluble KIR3DS1-Ig fusion proteins did not bind
      to EBV-transformed B lymphoid cell lines transfected with HLA-Bw4 80I or 80T
      allotypes, suggesting that if KIR3DS1 does recognize HLA-Bw4 ligands, this may be
      peptide dependent.

PMID- 17202324
TI  - Cutting Edge: Distinct NK receptor profiles are imprinted on CD8 T cells in the
      mucosa and periphery during the same antigen challenge: role of tissue-specific
      factors.
AB  - NK cell receptors (NKRs) modulate T lymphocyte responses by modifying the Ag
      activation threshold. However, what governs their expression on T cells remains
      unclear. In this study we show that different NKRs are imprinted on CD8 T cells
      in the gut mucosa and periphery during the same Ag challenge. After a viral,
      bacterial, and tumor challenge, most CD8 peritoneal exudate lymphocytes expressed
      NKG2A but not 2B4. In contrast, most CD8 intraepithelial lymphocytes exhibited
      2B4 but not NKG2A. Our data suggest that tissue-specific factors may determine
      the pattern of NKR expression. In the gut, CD70 licensing appears to promote 2B4
      induction on mucosal CD8 T cells. Conversely, retinoic acid produced by the
      intestinal dendritic cells may suppress NKG2A expression. Thus, tissue-specific
      factors regulate NKR expression and may confer T cells with differing effector
      functions in a tissue and site-specific manner.

PMID- 17202325
TI  - The varicellovirus-encoded TAP inhibitor UL49.5 regulates the presentation of CTL
      epitopes by Qa-1b1.
AB  - Impairment of MHC class I Ag processing is a commonly observed mechanism that
      allows viruses and tumors to escape immune destruction by CTL. The peptide
      transporter TAP that is responsible for the delivery of MHC class I-binding
      peptides into the endoplasmic reticulum is a pivotal target of viral-immune
      evasion molecules, and expression of this transporter is frequently lost in
      advanced cancers. We recently described a novel population of CTL that
      intriguingly exhibits reactivity against such tumor-immune escape variants and
      that recognizes self-peptides emerging at the cell surface due to defects in the
      processing machinery. Investigations of this new type of CTL epitopes are
      hampered by the lack of an efficient inhibitor for peptide transport in mouse
      cells. In this article, we demonstrate that the varicellovirus protein UL49.5, in
      contrast to ICP47 and US6, strongly impairs the activity of the mouse transporter
      and mediates degradation of mouse TAP1 and TAP2. Inhibition of TAP was witnessed
      by a strong reduction of surface MHC class I display and a decrease in
      recognition of conventional tumor-specific CTL. Analysis of CTL reactivity
      through the nonclassical molecule Qa-1(b) revealed that the presentation of the
      predominant leader peptide was inhibited. Interestingly, expression of UL49.5 in
      processing competent tumor cells induced the presentation of the new category of
      peptides. Our data show that the varicellovirus UL49.5 protein is a universal TAP
      inhibitor that can be exploited for preclinical studies on CTL-based immune
      intervention.

PMID- 17202326
TI  - Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal
      macrophages in type 2 diabetic mice is dependent on elevated glucose and requires
      p38 MAPK.
AB  - Dysregulated inflammation is a complication of type 2 diabetes (T2D). In this
      study, we show that augmented LPS-induced TNF-alpha production by resident
      peritoneal macrophages (PerMphi) in type 2 diabetic (db/db) mice is dependent on
      elevated glucose and requires p38 MAPK. Intraperitoneal LPS administered to db/db
      and nondiabetic (db/+) mice induced 3- and 4-fold more TNF-alpha in the
      peritoneum and serum, respectively, of db/db mice as compared with db/+ mice.
      Examination of the TLR-4/MD2 complex and CD14 expression showed no difference
      between db/db and db/+ PerMphi. Ex vivo stimulation of PerMphi with LPS produced
      a similar 3-fold increase in TNF-alpha production in db/db PerMphi when compared
      with db/+ PerMphi. PerMphi isolated from db/+ mice incubated in high glucose (4
      g/L) medium for 12 h produced nearly 2-fold more TNF-alpha in response to LPS
      than PerMphi incubated in normal glucose medium (1 g/L). LPS-dependent
      stimulation of PI3K activity, ERK1/2 activation, and p38 kinase activity was
      greater in PerMphi from db/db mice as compared with db/+ mice. Only inhibition of
      p38 kinase blocked LPS-induced TNF-alpha production in PerMphi from db/db mice.
      Taken together, these data indicate that augmented TNF-alpha production induced
      by LPS in macrophages during diabetes is due to hyperglycemia and increased LPS
      dependent activation of p38 kinase.

PMID- 17202327
TI  - A costimulatory function for T cell CD40.
AB  - CD40 plays a significant role in the pathogenesis of inflammation and
      autoimmunity. B cell CD40 directly activates cells, which can result in
      autoantibody production. T cells can also express CD40, with an increased
      frequency and amount of expression seen in CD4(+) T lymphocytes of autoimmune
      mice, including T cells from mice with collagen-induced arthritis. However, the
      mechanisms of T cell CD40 function have not been clearly defined. To test the
      hypothesis that CD40 can serve as a costimulatory molecule on T lymphocytes,
      CD40(+) T cells from collagen-induced arthritis mice were examined in parallel
      with mouse and human T cell lines transfected with CD40. CD40 served as
      effectively as CD28 in costimulating TCR-mediated activation, including induction
      of kinase and transcription factor activities and production of cytokines. An
      additional enhancement was seen when both CD40 and CD28 signals were combined
      with AgR stimulation. These findings reveal potent biologic functions for T cell
      CD40 and suggest an additional means for amplification of autoimmune responses.

PMID- 17202328
TI  - TCR activation eliminates glutamate receptor GluR3 from the cell surface of
      normal human T cells, via an autocrine/paracrine granzyme B-mediated proteolytic
      cleavage.
AB  - The majority of resting normal human T cells, like neuronal cells, express
      functional receptors for glutamate (the major excitatory neurotransmitter in the
      CNS) of the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA)-receptor subtype 3 (GluR3). Glutamate by itself ( approximately 10 nM)
      activates key T cell functions, including adhesion to fibronectin and laminin and
      chemotactic migration toward CXCL12/stromal cell-derived factor 1. In this study,
      we found by GluR3-specific immunostaining, flow cytometry, and Western blots that
      GluR3 cell surface expression decreases dramatically following TCR activation of
      human T cells. CXCR4, VLA-4, and VLA-6 also decrease substantially, whereas CD147
      increases as expected, after TCR activation. Media of TCR-activated cells
      "eliminates" intact GluR3 (but not CXCR4 and VLA-6) from the cell surface of
      resting T cells, suggesting GluR3 cleavage by a soluble factor. We found that
      this factor is granzyme B (GB), a serine protease released by TCR-activated
      cells, because the extent of GluR3 elimination correlated with the active GB
      levels, and because three highly specific GB inhibitors blocked GluR3 down
      regulation. Media of TCR-activated cells, presumably containing cleaved GluR3B
      peptide (GluR3 aa 372-388), inhibited the specific binding of anti-GluR3B mAb to
      synthetic GluR3B peptide. In parallel to losing intact GluR3, TCR-activated cells
      lost glutamate-induced adhesion to laminin. Taken together, our study shows that
      "classical immunological" TCR activation, via autocrine/paracrine GB, down
      regulates substantially the expression of specific neurotransmitter receptors.
      Accordingly, glutamate T cell neuroimmune interactions are influenced by the T
      cell activation state, and glutamate, via AMPA-GluR3, may activate only resting,
      but not TCR-activated, T cells. Finally, the cleavage and release to the
      extracellular milieu of the GluR3B peptide may in principle increase its
      antigenicity, and thus the production, of anti-self GluR3B autoantibodies, which
      activate and kill neurons, found in patients with various types of epilepsy.

PMID- 17202329
TI  - TLR9-signaling pathways are involved in Kilham rat virus-induced autoimmune
      diabetes in the biobreeding diabetes-resistant rat.
AB  - Viral infections are associated epidemiologically with the expression of type 1
      diabetes in humans, but the mechanisms underlying this putative association are
      unknown. To investigate the role of viruses in diabetes, we used a model of viral
      induction of autoimmune diabetes in genetically susceptible biobreeding diabetes
      resistant (BBDR) rats. BBDR rats do not develop diabetes in viral-Ab-free
      environments, but approximately 25% of animals infected with the parvovirus
      Kilham rat virus (KRV) develop autoimmune diabetes via a mechanism that does not
      involve beta cell infection. Using this model, we recently documented that TLR
      agonists synergize with KRV infection and increase disease penetrance. We now
      report that KRV itself activates innate immunity through TLR ligation. We show
      that KRV infection strongly stimulates BBDR splenocytes to produce the
      proinflammatory cytokines IL-6 and IL-12p40 but not TNF-alpha. KRV infection
      induces high levels of IL-12p40 by splenic B cells and Flt-3-ligand-induced bone
      marrow-derived dendritic cells (DCs) but only low levels of IL-12p40 production
      by thioglycolate-elicited peritoneal macrophages or GM-CSF plus IL-4-induced bone
      marrow-derived DCs. KRV-induced cytokine production is blocked by pharmacological
      inhibitors of protein kinase R and NF-kappaB. Genomic KRV DNA also induces BBDR
      splenocytes and Flt-3L-induced DCs from wild-type but not TLR9-deficient mice to
      produce IL-12p40; KRV-induced up-regulation of B lymphocytes can be blocked by
      TLR9 antagonists including inhibitory CpG and chloroquine. Administration of
      chloroquine to virus-infected BBDR rats decreases the incidence of diabetes and
      decreases blood levels of IL-12p40. Our data implicate the TLR9-signaling pathway
      in KRV-induced innate immune activation and autoimmune diabetes in the BBDR rat.

PMID- 17202330
TI  - Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell
      stimulatory function of dendritic cells.
AB  - Signaling through the PGI(2) receptor (IP) has been shown to inhibit inflammatory
      responses in mouse models of respiratory syncytial viral infection and OVA
      induced allergic responses. However, little is known about the cell types that
      mediate the anti-inflammatory function of PGI(2.) In this study, we determined
      that PGI(2) analogs modulate dendritic cell (DC) cytokine production, maturation,
      and function. We report that PGI(2) analogs (iloprost, cicaprost, treprostinil)
      differentially modulate the response of murine bone marrow-derived DC (BMDC) to
      LPS in an IP-dependent manner. The PGI(2) analogs decreased BMDC production of
      proinflammatory cytokines (IL-12, TNF-alpha, IL-1alpha, IL-6) and chemokines (MIP
      1alpha, MCP-1) and increased the production of the anti-inflammatory cytokine IL
      10 by BMDCs. The modulatory effect was associated with IP-dependent up-regulation
      of intracellular cAMP and down-regulation of NF-kappaB activity. Iloprost and
      cicaprost also suppressed LPS-induced expression of CD86, CD40, and MHC class II
      molecules by BMDCs and inhibited the ability of BMDCs to stimulate Ag-specific
      CD4 T cell proliferation and production of IL-5 and IL-13. These findings suggest
      that PGI(2) signaling through the IP may exert anti-inflammatory effects by
      acting on DC.

PMID- 17202331
TI  - Two groups of porcine TCRgammadelta+ thymocytes behave and diverge differently.
AB  - Developmental pathways of gammadelta T cells are still unknown, largely because
      of the absence of recognized lineage-specific surface markers other than the TCR.
      We have shown that porcine gammadelta thymocytes can be divided into 12 subsets
      of the following two major groups: 1) CD4(-) gammadelta thymocytes that can be
      further subdivided according to their CD2/CD8alphaalpha phenotype, and 2) CD4(+)
      gammadelta thymocytes that are always CD1(+)CD2(+)CD8alphabeta(+) and have no
      counterpart in the periphery. In this study, we have analyzed gammadelta
      thymocyte subsets with respect to behavior during cultivation, cell cycle status,
      and lymphocyte-specific transcripts. The group of CD4(-) gammadelta thymocytes
      gives rise to all gammadelta T cells found in the periphery. Proliferating
      CD2(+)CD8(-)CD1(+)CD45RC(-) gammadelta thymocytes are a common precursor of this
      group. These precursors differentiate into CD2(+)CD8alphaalpha(+), CD2(+)CD8(-),
      and CD2(-)CD8(-) gammadelta T cell subsets, which subsequently mature by loss of
      CD1 and by eventual gain of CD45RC expression. In contrast, the group of CD4(+)
      gammadelta thymocytes represents transient and independent subsets that are never
      exported from thymus as TCRgammadelta(+) T cells. In accordance with the
      following findings, we propose that CD4(+)CD8alphabeta(+) gammadelta thymocytes
      extinguish their TCRgammadelta expression and differentiate along the alphabeta T
      cell lineage program: 1) CD4(+) gammadelta thymocytes are actively dividing; 2)
      CD4(+) gammadelta thymocytes do not die, although their numbers decreased with
      prolonged cultivation; 3) CD4(+) gammadelta thymocytes express transcripts for
      RAG-1, TdT, and TCRbeta; and 4) CD4(+) gammadelta thymocytes are able to alter
      their phenotype to TCRalphabeta(+) thymocytes under appropriate culture
      conditions.

PMID- 17202333
TI  - IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T
      lymphocytes.
AB  - High expression of IL-21 and/or IL-21R has been described in T cell-mediated
      inflammatory diseases characterized by defects of counterregulatory mechanisms.
      CD4(+)CD25(+) regulatory T cells (Treg) are a T cell subset involved in the
      control of the immune responses. A diminished ability of these cells to inhibit T
      cell activation has been documented in immune-inflammatory diseases, raising the
      possibility that inflammatory stimuli can block the regulatory properties of
      Treg. We therefore examined whether IL-21 controls CD4(+)CD25(+) T cell function.
      We demonstrate in this study that IL-21 markedly enhances the proliferation of
      human CD4(+)CD25(-) T cells and counteracts the suppressive activities of
      CD4(+)CD25(+) T cells on CD4(+)CD25(-) T cells without affecting the percentage
      of Foxp3(+) cells or survival of Treg. Additionally, CD4(+)CD25(+) T cells
      induced in the presence of IL-21 maintain the ability to suppress alloresponses.
      Notably, IL-21 enhances the growth of CD8(+)CD25(-) T cells but does not revert
      the CD4(+)CD25(+) T cell-mediated suppression of this cell type, indicating that
      IL-21 makes CD4(+) T cells resistant to suppression rather than inhibiting
      CD4(+)CD25(+) T cell activity. Finally, we show that IL-2, IL-7, and IL-15, but
      not IL-21, reverse the anergic phenotype of CD4(+)CD25(+) T cells. Data indicate
      that IL-21 renders human CD4(+)CD25(-) T cells resistant to Treg-mediated
      suppression and suggest a novel mechanism by which IL-21 could augment T cell
      activated responses in human immune-inflammatory diseases.

PMID- 17202332
TI  - Guanosine inhibits CD40 receptor expression and function induced by cytokines and
      beta amyloid in mouse microglia cells.
AB  - Growing evidence implicates CD40, a member of the TNFR superfamily, as
      contributing to the pathogenesis of many neurodegenerative diseases. Thus,
      strategies to suppress its expression may be of benefit in those disorders. To
      this aim, we investigated the effect of guanosine, a purine nucleoside that
      exerts neurotrophic and neuroprotective effects. CD40 expression and function are
      increased by exposure of mouse microglia cultures or the N9 microglia cell line
      to IFN-gamma (10 ng/ml) plus TNF-alpha (50 ng/ml) or beta amyloid (Abeta) peptide
      (Abeta(1-42); 500 nM). Culture pretreatment with guanosine (10-300 microM),
      starting 1 h before cytokine or Abeta addition, dose-dependently inhibited the
      CD40-induced expression as well as functional CD40 signaling by suppressing IL-6
      production promoted by IFN-gamma/TNF-alpha challenge in the presence of CD40
      cross-linking. Moreover, guanosine abrogated IFN-gamma-induced phosphorylation on
      Ser(727) and translocation of STAT-1alpha to the nucleus as well as TNF-alpha
      /Abeta-induced IkappaBalpha and NF-kappaB p65/RelA subunit phosphorylation, thus
      inhibiting NF-kappaB-induced nuclear translocation. Guanosine effects were
      mediated by an increased phosphorylation of Akt, a PI3K downstream effector, as
      well as of ERK1/2 and p38 in the MAPK system, because culture pretreatment with
      selective ERK1/2, p38 MAPK, and PI3K antagonists (U0126, SB203580, or LY294002,
      respectively) counteracted guanosine inhibition on IFN-gamma/TNF-alpha-induced
      CD40 expression and function as well as on STAT-1alpha or NF-kappaB nuclear
      translocation. These findings suggest a role for guanosine as a potential drug in
      the experimental therapy of neuroinflammatory/neurodegenerative diseases,
      particularly Alzheimer's disease.

PMID- 17202334
TI  - B cell receptor signaling down-regulates forkhead box transcription factor class
      O 1 mRNA expression via phosphatidylinositol 3-kinase and Bruton's tyrosine
      kinase.
AB  - BCR cross-linking promotes mature B cell proliferation and survival. PI3K
      mediated down-regulation of proapoptotic and antimitogenic genes such as forkhead
      box transcription factor class O 1 (FOXO1) is an important component of this
      process. Previously, BCR-induced phosphorylation of FOXO1 was shown to lead to a
      block in nuclear localization and subsequent protein degradation. We demonstrate
      that the BCR also signals through PI3K to down-regulate FOXO1 mRNA expression.
      Bruton's tyrosine kinase (Btk), a downstream effector of PI3K, signals through B
      cell linker protein (BLNK) and phospholipase C (PLC)gamma2 to mediate B cell
      proliferation and survival in response to BCR cross-linking. BCR-induced down
      regulation of FOXO1 mRNA was impaired in murine knockouts of Btk, BLNK, and
      PLCgamma2. Because B cells in these models are predominantly immature,
      experiments were also performed using mature B cells expressing low levels of Btk
      and BLNK. Similar results were obtained. Inhibitors of downstream components of
      the Btk/BLNK/PLCgamma2 pathway were used to define the mechanism by which Btk
      signaling inhibits FOXO1 expression. The protein kinase Cbeta inhibitor Go6850
      had minimal effects on BCR-mediated FOXO1 mRNA down-regulation. However,
      cyclosporin A, an inhibitor of the Ca(2+)-dependent phosphatase calcineurin, had
      similar effects on FOXO1 mRNA expression as the PI3K inhibitor LY294002. Neither
      Btk deficiency nor cyclosporin A prevented FOXO1 protein phosphorylation,
      indicating that PI3K down-regulates FOXO1 via two independent pathways. We show
      that the Btk/BLNK/PLCgamma2 pathway mediates BCR-induced changes in expression of
      the FOXO1 target gene cyclin G2. These observations support the hypothesis that
      Btk mediates BCR-induced proliferation and survival in part via inhibition of
      FOXO expression.

PMID- 17202336
TI  - Enforced expression of Bcl-2 partially restores cell numbers but not functions of
      TCRgammadelta intestinal intraepithelial T lymphocytes in IL-15-deficient mice.
AB  - IL-15 knockout (KO) mice have severely reduced numbers of TCRgammadelta
      intestinal intraepithelial T lymphocytes (i-IEL), suggesting requirements of IL
      15 signaling in the development or maintenance of i-IEL. To determine an
      involvement of survival signals via Bcl-2 in IL-15-mediated homeostasis of
      TCRgammadelta i-IEL, we introduced a bcl-2 transgene into IL-15 KO mice. In situ
      apoptosis of TCRgammadelta i-IEL was decreased in Bcl-2 transgenic (Tg) x IL-15
      KO mice compared with IL-15 KO mice. The enforced expression of Bcl-2 partially
      restored the numbers of TCRgammadelta i-IEL in IL-15 KO mice. However, effector
      functions of TCRgammadelta i-IEL, including cytokine production and cytotoxic
      activity, were not recovered in Bcl-2 Tg x IL-15 KO mice. Importantly,
      TCRgammadelta i-IEL in Bcl-2 Tg x IL-15 KO mice expressed a reduced level of
      eomesodermin, a transcription factor critical for effector functions of NK cells
      and CD8(+) T cells. Similar to the case of TCRgammadelta i-IEL, enforced
      expression of Bcl-2 restored the numbers but not the functions of NK cells in IL
      15 KO mice. These results suggest that Bcl-2-mediated survival signal is involved
      in the IL-15-mediated homeostasis of TCRgammadelta i-IEL and NK cells, but other
      signals from IL-15 are critical for inducing transcription factors, such as
      eomesodermin for their effector functions.

PMID- 17202337
TI  - Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-bearing
      adapters DAP12 and FcRgamma chain on peritoneal macrophages.
AB  - Certain activating immune receptors expressed on myeloid cells noncovalently
      associate with either DAP12 or FcepsilonRIgamma (FcRgamma chain), the ITAM
      bearing transmembrane adapter proteins. An activating receptor, myeloid
      associated Ig-like receptor (MAIR) II, is expressed on a subset of B cells and
      macrophages in the spleen and peritoneal cavity of mice and associates with DAP12
      in these cells. However, we demonstrate here that cross-linking MAIR-II with mAb
      induced secretion of a significant amount of the inflammatory cytokines TNF-alpha
      and IL-6 from DAP12(-/-) as well as wild-type (WT) peritoneal macrophages. We
      show that MAIR-II associates with not only DAP12 but also FcRgamma chain
      homodimers in peritoneal macrophages. LPS enhanced the FcRgamma chain expression
      and FcRgamma chain-dependent cell surface expression of MAIR-II and had additive
      effects on MAIR-II-mediated inflammatory cytokine secretion from peritoneal
      macrophages. The lysine residue in the transmembrane region of MAIR-II was
      involved in the association with FcRgamma chain as well as DAP12. Our findings
      present the first case of an activating receptor that uses either DAP12 or
      FcRgamma chain as a signaling adapter. The FcRgamma chain may provide cooperation
      with and/or compensation for DAP12 in MAIR-II-mediated inflammatory responses by
      peritoneal macrophages.

PMID- 17202335
TI  - The extra domain A from fibronectin targets antigens to TLR4-expressing cells and
      induces cytotoxic T cell responses in vivo.
AB  - Vaccination strategies based on the in vivo targeting of Ags to dendritic cells
      (DCs) are needed to improve the induction of specific T cell immunity against
      tumors and infectious agents. In this study, we have used a recombinant protein
      encompassing the extra domain A from fibronectin (EDA), an endogenous ligand for
      TLR4, to deliver Ags to TLR4-expressing DC. The purified EDA protein was shown to
      bind to TLR4-expressing HEK293 cells and to activate the TLR4 signaling pathway.
      EDA also stimulated the production by DC of proinflammatory cytokines such as IL
      12 or TNF-alpha and induced their maturation in vitro and in vivo. A fusion
      protein between EDA and a cytotoxic T cell epitope from OVA efficiently presented
      this epitope to specific T cells and induced the in vivo activation of a strong
      and specific CTL response. Moreover, a fusion protein containing EDA and the full
      OVA also improved OVA presentation by DC and induced CTL responses in vivo. These
      EDA recombinant proteins protected mice from a challenge with tumor cells
      expressing OVA. These results strongly suggest that the fibronectin extra domain
      A may serve as a suitable Ag carrier for the development of antiviral or
      antitumoral vaccines.

PMID- 17202338
TI  - Klotho--a common link in physiological and rheumatoid arthritis-related aging of
      human CD4+ lymphocytes.
AB  - Human CD4(+) T lymphocytes undergo aging-related changes leading to decreased
      immunity to infections and neoplasms, and to increased frequency of autoimmune
      diseases including rheumatoid arthritis (RA). Certain changes, observed in the
      CD4(+) cells of RA patients, resemble those observed during physiological aging,
      but occur at earlier age. Underlying cellular mechanism(s) of these similarities
      are so far largely unknown. Here we show that KLOTHO, a beta-glucuronidase gene
      whose activity changes are associated with aging phenotype, is down-regulated at
      the mRNA, protein, and enzymatic (beta-glucuronidase) activity levels both in the
      healthy elderly and especially in RA CD4(+) lymphocytes. Although the exact role
      of Klotho activity for CD4(+) cell function is unknown, we propose here that it
      might be involved in anti-inflammatory processes occurring in the young and
      healthy individuals, but reduced in both healthy elderly and RA patients. To
      support this hypothesis, we show here that the reduction of Klotho expression and
      activity in both elderly and patients' lymphocytes occurs in concert with the
      down-regulation of T cell costimulatory molecule CD28, the latter known to be
      dependent on increased levels of TNF-alpha. Thus, a common mechanism of KLOTHO
      down-regulation, but executed at various times in life, may underlie both
      physiological and disease-related T cell aging. Klotho activity might become a
      target of anti-RA drug development as well as a tool to help increase the immune
      system efficiency in the elderly.

PMID- 17202339
TI  - Chemokine-guided CD4+ T cell help enhances generation of IL-6RalphahighIL-7Ralpha
      high prememory CD8+ T cells.
AB  - CD4(+) T cells promote effective CD8(+) T cell-mediated immunity, but the timing
      and mechanistic details of such help remain controversial. Furthermore, the
      extent to which innate stimuli act independently of help in enhancing CD8(+) T
      cell responses is also unresolved. Using a noninfectious vaccine model in
      immunocompetent mice, we show that even in the presence of innate stimuli, CD4(+)
      T cell help early after priming is required for generating an optimal pool of
      functional memory CD8(+) T cells. CD4(+) T cell help increased the size of a
      previously unreported population of IL-6Ralpha(high)IL-7Ralpha(high) prememory
      CD8(+) T cells shortly after priming that showed a survival advantage in vivo and
      contributed to the majority of functional memory CD8(+) T cells after the
      contraction phase. In accord with our recent demonstration of chemokine-guided
      recruitment of naive CD8(+) T cells to sites of CD4(+) T cell-dendritic cell
      interactions, the generation of IL-6Ralpha(high)IL-7Ralpha(high) prememory as
      well as functional memory CD8(+) T cells depended on the early postvaccination
      action of the inflammatory chemokines CCL3 and CCL4. Together, these findings
      support a model of CD8(+) T cell memory cell differentiation involving the
      delivery of key signals early in the priming process based on chemokine-guided
      attraction of naive CD8(+) T cells to sites of Ag-driven interactions between TLR
      activated dendritic cells and CD4(+) T cells. They also reveal that elevated IL
      6Ralpha expression by a subset of CD8(+) T cells represents an early imprint of
      CD4(+) T cell helper function that actively contributes to the survival of
      activated CD8(+) T cells.

PMID- 17202340
TI  - The duration of exposure to HIV modulates the breadth and the magnitude of HIV
      specific memory CD4+ T cells.
AB  - The impact of exposure to Ag on the development and maintenance of human CD4(+)
      memory T cells in general and HIV infection in particular is partially
      understood. In this study, we measured HIV-specific CD4(+) T cell proliferative
      responses against HIV proteins and derived peptides one year after highly active
      antiretroviral therapy initiation in 39 HIV-infected patients who initiated
      therapy at different times following infection. We show that a brief exposure to
      HIV of <1 month does not allow the generation of significant detectable
      frequencies of HIV-specific CD4(+) memory T cells. Patients having prolonged
      cumulative exposure to high viral load due to therapy failures also demonstrated
      limited HIV-specific CD4(+) T cell responses. In contrast, patients exposed to
      significant levels of virus for periods ranging from 3 to 18 mo showed brisk and
      broad HIV-specific CD4(+) T cell responses 1 year following the onset of therapy
      intervention. We also demonstrate that the nadir CD4(+) T cell count before
      therapy initiation correlated positively with the breadth and magnitude of these
      responses. Our findings indicate that the loss of proliferative HIV-specific
      CD4(+) T cell responses is associated with the systemic progression of the
      disease and that a brief exposure to HIV does not allow the establishment of
      detectable frequencies of HIV-specific memory CD4(+) T cells.

PMID- 17202341
TI  - IL-10 regulation by HIV-Tat in primary human monocytic cells: involvement of
      calmodulin/calmodulin-dependent protein kinase-activated p38 MAPK and Sp-1 and
      CREB-1 transcription factors.
AB  - The anti-inflammatory cytokine, IL-10 plays an important role in HIV
      immunopathogenesis. The HIV accessory protein, Tat is not only critical for viral
      replication, but affects the host immune system by influencing cytokine
      production including IL-10. During HIV infection, IL-10 production by monocytic
      cells is up-regulated, representing a critical pathway by which HIV may induce
      immunodeficiency. Herein, we show that extracellular Tat-induced IL-10 expression
      in normal human monocytes. To understand the signaling pathways underlying HIV
      Tat induced IL-10 transcription, we investigated the involvement of MAPK as well
      as calcium signaling and the downstream transcription factor(s). Our results
      suggest that Tat-induced calcium influx regulated IL-10 transcription in
      monocytic cells. The experiments designed to further understand the molecules
      involved in the calcium signaling suggested that calmodulin and calmodulin
      dependent protein kinase-II (CaMK-II)-activated p38 MAPK played a role in
      extracellular Tat-induced IL-10 expression in primary human monocytes.
      Furthermore, Tat-induced IL-10 expression was regulated by p38 MAPK- and CaMK II
      activated CREB-1 as well as Sp-1 transcription factors. Taken together, our
      results suggest that extracellular HIV-Tat induced IL-10 transcription in primary
      human monocytes is regulated by CREB-1 and Sp-1 transcription factors through the
      activation of calmodulin/CaMK-II-dependent p38 MAPK.

PMID- 17202342
TI  - The IREM-1 (CD300f) inhibitory receptor associates with the p85alpha subunit of
      phosphoinositide 3-kinase.
AB  - The immune receptor expressed by myeloid cell 1 (IREM-1) (CD300f) inhibitory
      receptor displays five cytoplasmic tyrosine residues, two of them (Y205 and Y249)
      fit with ITIMs, whereas Y236 and Y263 constitute putative binding sites for PI3K.
      In the present study, immunoprecipitation analysis revealed that both the
      p85alpha subunit of PI3K and Src homology region 2 domain-containing phosphatase
      1 could be recruited by IREM-1 in transfected cells as well as in the U937
      monocytic leukemia cells, which constitutively express the receptor. By assaying
      the ability of different IREM-1 mutants to regulate the secretion of beta
      hexosaminidase induced via FcRepsilonI in rat basophilic leukemia cells, both
      Y205 and Y249 appeared crucial for IREM-1-mediated inhibition. Remarkably,
      engagement of an IREM-1 mutant (Y(205,249,284)F), which did not recruit Src
      homology region 2 domain-containing phosphatase-1 and lost its inhibitory
      function, induced rat basophilic leukemia cell degranulation. This effect was
      dependent on the recruitment of PI3K, requiring the integrity of Y236 and Y263,
      and was blocked by PI3K inhibitors (i.e., wortmannin and LY-294002). Altogether,
      these data reveal a putative functional duality of the IREM-1 myeloid cell
      receptor.

PMID- 17202343
TI  - SAP regulation of follicular helper CD4 T cell development and humoral immunity
      is independent of SLAM and Fyn kinase.
AB  - Mutations in SH2D1A resulting in lack of SLAM-associated protein (SAP) expression
      cause the human genetic immunodeficiency X-linked lymphoproliferative disease. A
      severe block in germinal center development and lack of long-term humoral
      immunity is one of the most prominent phenotypes of SAP(-) mice. We show, in this
      study, that the germinal center block is due to an essential requirement for SAP
      expression in Ag-specific CD4 T cells to develop appropriate follicular helper T
      cell functions. It is unknown what signaling molecules are involved in regulation
      of SAP-dependent CD4 T cell help functions. SAP binds to the cytoplasmic tail of
      SLAM, and we show that SLAM is expressed on resting and activated CD4 T cells, as
      well as germinal center B cells. In addition, SAP can recruit Fyn kinase to SLAM.
      We have now examined the role(s) of the SLAM-SAP-Fyn signaling axis in in vivo
      CD4 T cell function and germinal center development. We observed normal germinal
      center development, long-lived plasma cell development, and Ab responses in SLAM(
      /-) mice after a viral infection (lymphocytic choriomeningitis virus). In a
      separate series of experiments, we show that SAP is absolutely required in CD4 T
      cells to drive germinal center development, and that requirement does not depend
      on SAP-Fyn interactions, because CD4 T cells expressing SAP R78A are capable of
      supporting normal germinal center development. Therefore, a distinct SAP
      signaling pathway regulates follicular helper CD4 T cell differentiation,
      separate from the SLAM-SAP-Fyn signaling pathway regulating Th1/Th2
      differentiation.

PMID- 17202344
TI  - Thymus medulla formation and central tolerance are restored in IKKalpha-/- mice
      that express an IKKalpha transgene in keratin 5+ thymic epithelial cells.
AB  - Medullary thymic epithelial cells (mTECs) play an essential role in establishing
      central tolerance due to their unique capacity to present a diverse array of
      tissue restricted Ags that induce clonal deletion of self-reactive thymocytes.
      One mTEC subset expresses keratin 5 (K5) and K14, but fails to bind Ulex
      europaeus agglutinin-1 (UEA-1) lectin. A distinct mTEC subset binds UEA-1 and
      expresses K8, but not K5 or K14. Development of both mTEC subsets requires
      activation of the noncanonical NF-kappaB pathway. In this study, we show that
      mTEC development is severely impaired and autoimmune manifestations occur in mice
      that are deficient in IkappaB kinase (IKK)alpha, a required intermediate in the
      noncanonical NF-kappaB signaling pathway. Introduction of an IKKalpha transgene
      driven by a K5 promoter restores the K5(+)K14(+) mTEC subset in IKKalpha(-/-)
      mice. Unexpectedly, the K5-IKKalpha transgene also rescues the UEA-1 binding mTEC
      subset even though K5 expression is not detectable in these cells. In addition,
      expression of the K5-IKKalpha transgene ameliorates autoimmune symptoms in
      IKKalpha(-/-) mice. These data suggest that 1) medulla formation and central
      tolerance depend on activating the alternative NF-kappaB signaling pathway
      selectively in K5-expressing mTECs and 2) the K5-expressing subset either
      contains immediate precursors of UEA-1 binding cells or indirectly induces their
      development.

PMID- 17202345
TI  - Donor CD8+ T cells mediate graft-versus-leukemia activity without clinical signs
      of graft-versus-host disease in recipients conditioned with anti-CD3 monoclonal
      antibody.
AB  - Donor CD8(+) T cells play a critical role in mediating graft-vs-leukemia (GVL)
      activity, but also induce graft-vs-host disease (GVHD) in recipients conditioned
      with total body irradiation (TBI). In this study, we report that injections of
      donor C57BL/6 (H-2(b)) or FVB/N (H-2(q)) CD8(+) T with bone marrow cells induced
      chimerism and eliminated BCL1 leukemia/lymphoma cells without clinical signs of
      GVHD in anti-CD3-conditioned BALB/c (H-2(d)) recipients, but induced lethal GVHD
      in TBI-conditioned recipients. Using in vivo and ex vivo bioluminescent imaging,
      we observed that donor CD8(+) T cells expanded rapidly and infiltrated GVHD
      target tissues in TBI-conditioned recipients, but donor CD8(+) T cell expansion
      in anti-CD3-conditioned recipients was confined to lymphohematological tissues.
      This confinement was associated with lack of up-regulated expression of
      alpha(4)beta(7) integrin and chemokine receptors (i.e., CXCR3) on donor CD8(+) T
      cells. In addition, donor CD8(+) T cells in anti-CD3-conditioned recipients were
      rendered unresponsive, anergic, Foxp3(+), or type II cytotoxic T phenotype. Those
      donor CD8(+) T cells showed strong suppressive activity in vitro and mediated GVL
      activity without clinical signs of GVHD in TBI-conditioned secondary recipients.
      These results indicate that anti-CD3 conditioning separates GVL activity from
      GVHD via confining donor CD8(+) T cell expansion to host lymphohemological
      tissues as well as tolerizing them in the host.

PMID- 17202346
TI  - Intercellular adhesion molecule-1 expression is required on multiple cell types
      for the development of experimental autoimmune encephalomyelitis.
AB  - Many members of the Ig superfamily of adhesion molecules, such as ICAM-1 and VCAM
      1, have been implicated in the pathogenesis of multiple sclerosis. Although it is
      well-established that VCAM-1/VLA-4 interactions can play important roles in
      mediating CNS inflammatory events in multiple sclerosis patients and during the
      development of experimental allergic encephalomyelitis (EAE), the contributions
      of ICAM-1 are poorly understood. This is due in large part to conflicting results
      from Ab inhibition studies and the observation of exacerbated EAE in ICAM-1
      mutant mice that express a restricted set of ICAM-1 isoforms. To determine ICAM-1
      mediated mechanisms in EAE, we analyzed ICAM-1 null mutant mice (ICAM-1(null)),
      which express no ICAM-1 isoforms. ICAM-1(null) mice had significantly attenuated
      EAE characterized by markedly reduced spinal cord T cell infiltration and IFN
      gamma production by these cells. Adoptive transfer of Ag-restimulated T cells
      from wild-type to ICAM-1(null) mice or transfer of ICAM-1(null) Ag-restimulated T
      cells to control mice failed to induce EAE. ICAM-1(null) T cells also showed
      reduced proliferative capacity and substantially reduced levels of IFN-gamma, TNF
      alpha, IL-4, IL-10, and IL-12 compared with that of control T cells following
      myelin oligodendrocyte glycoprotein 35-55 restimulation in vitro. Our results
      indicate that ICAM-1 expression is critical on T cells and other cell types for
      the development of demyelinating disease and suggest that expression of VCAM-1
      and other adhesion molecules cannot fully compensate for the loss of ICAM-1
      during EAE development.

PMID- 17202347
TI  - Bone marrow-derived hemopoietic precursors commit to the T cell lineage only
      after arrival in the thymic microenvironment.
AB  - T lymphocytes develop in the thymus from hemopoietic precursors that commit to
      the T cell lineage under the influence of Notch signals. In this study, we show
      by single cell analyses that the most immature hemopoietic precursors in the
      adult mouse thymus are uncommitted and specify to the T cell lineage only after
      their arrival in the thymus. These precursors express high levels of surface
      Notch receptors and rapidly lose B cell potential upon the provision of Notch
      signals. Using a novel culture system with complexed, soluble Notch ligands that
      allows the titration of T cell lineage commitment, we find that these precursors
      are highly sensitive to both Delta and Jagged ligands. In contrast, their
      phenotypical and functional counterparts in the bone marrow are resistant to
      Notch signals that efficiently induce T cell lineage commitment in thymic
      precursors. Mechanistically, this is not due to differences in receptor
      expression, because early T lineage precursors, bone marrow lineage marker
      negative, Sca-1-positive, c-Kit-positive and common lymphoid progenitor cells,
      express comparable amounts of surface Notch receptors. Our data demonstrate that
      the sensitivity to Notch-mediated T lineage commitment is stage-dependent and
      argue against the bone marrow as the site of T cell lineage commitment.

PMID- 17202348
TI  - HIV-1 trans activator of transcription protein elicits mitochondrial
      hyperpolarization and respiratory deficit, with dysregulation of complex IV and
      nicotinamide adenine dinucleotide homeostasis in cortical neurons.
AB  - HIV-1 causes a common, progressive neurological disorder known as HIV-associated
      dementia (HAD). The prevalence of this disorder has increased despite the use of
      highly active antiretroviral therapy, and its underlying pathogenesis remains
      poorly understood. However, evidence suggests that some aspects of HAD may be
      reversible. To model the reversible aspects of HAD, we have used the HIV-1
      neurotoxin trans activator of transcription protein (Tat) to investigate
      nonlethal changes in cultured neurons. Exposure of rodent cortical neurons to
      sublethal concentrations of Tat elicits mitochondrial hyperpolarization. In this
      study, we used the cationic lipophilic dye rhodamine 123 to confirm this
      observation, and then performed follow-up studies to examine the mechanism
      involved. In intact neurons, we found Tat elicited a rapid drop in internal
      mitochondrial pH, and addition of Tat to purified mitochondrial extracts
      inhibited complex IV of the electron transport chain. To correlate enzyme
      activity in mitochondrial extracts with results in intact cells, we measured
      neuronal respiration following Tat exposure. Cortical neurons demonstrated
      decreased respiration upon Tat treatment, consistent with inhibition of complex
      IV. We examined mitochondrial Ca(2+) homeostasis using a mitochondrial targeted
      enhanced yellow fluorescent protein-calmodulin construct. We detected a decrease
      in mitochondrial calcium concentration following exposure to Tat. Finally, we
      measured the energy intermediate NAD(P)H after Tat treatment, and found a 20%
      decrease in the autofluorescence. Based on these findings, we suggest that
      decreased NADPH and calcium concentration contribute to subsequent respiratory
      decline after exposure to Tat, with detrimental effects on neuronal signaling.

PMID- 17202349
TI  - Alteration of the migratory behavior of UV-induced regulatory T cells by tissue
      specific dendritic cells.
AB  - UV radiation-induced regulatory T cells (UV-Treg) inhibit the sensitization but
      not the elicitation of contact hypersensitivity when injected i.v. Because UV
      Treg express the lymph node homing receptor CD62 ligand, upon i.v. injection they
      migrate into the lymph nodes but not into the periphery and therefore inhibit
      sensitization but not elicitation. We tried to modify the migratory behavior of
      UV-Treg with the aim to get them into the periphery and thereby to suppress the
      effector phase of immune reactions. Because the tissue selective homing of T
      effector cells is determined by tissue-specific dendritic cells (DC), we
      attempted to reprogram the migratory behavior of UV-Treg by DC. 2,4
      Dinitrofluorobencene (DNFB)-specific UV-Treg coincubated with epidermal
      Langerhans cells (LC) blocked the elicitation upon i.v. injection into DNFB
      sensitized mice. In contrast, i.v. injection of UV-Treg not incubated with LC did
      not inhibit the ear challenge. The same negative effect was observed for UV-Treg
      coincubated with DC from bone marrow, spleen, or lymph nodes. This effect was not
      due to different maturation stages as checked by MHC class II expression of the
      different DC types. Incubation with LC but not with bone marrow-derived DC down
      regulated the expression of CD62 ligand on UV-Treg. Accordingly, CFDA-SE labeled
      UV-Treg coincubated with LC were found in the ears but not in the lymph nodes
      upon i.v. injection. This finding shows that the migratory behavior can be
      reprogrammed by tissue-specific DC and may have input on strategies trying to use
      Treg not only for the prevention but also for the treatment of immune-mediated
      diseases.

PMID- 17202350
TI  - Regulatory T cells maintain long-term tolerance to myelin basic protein by
      inducing a novel, dynamic state of T cell tolerance.
AB  - The pathogenesis of multiple sclerosis involves a breakdown in T cell tolerance
      to myelin proteins like myelin basic protein (MBP). Most MBP-specific T cells are
      eliminated by central tolerance in adult mice, however, the developmentally
      regulated expression of MBP allows MBP-specific thymocytes in young mice to
      escape negative selection. It is not known how these T cells that encounter MBP
      for the first time in the periphery are regulated. We show that naive MBP
      specific T cells transferred into T cell-deficient mice induce severe
      autoimmunity. Regulatory T cells prevent disease, however, suppression of the
      newly transferred MBP-specific T cells is abrogated by activating APCs in vivo.
      Without APC activation, MBP-specific T cells persist in the periphery of
      protected mice but do not become anergic, raising the question of how long-term
      tolerance can be maintained if APCs presenting endogenous MBP become activated.
      Our results demonstrate that regulatory T cells induce naive MBP-specific T cells
      responding to nonactivated APCs to differentiate into a unique, tolerized state
      with the ability to produce IL-10 and TGF-beta1 in response to activated, but not
      nonactivated, APCs presenting MBP. This tolerant response depends on continuous
      activity of regulatory T cells because, in their absence, these uniquely
      tolerized MBP-specific T cells can again induce autoimmunity.

PMID- 17202351
TI  - FcgammaRIIB regulates autoreactive primary antibody-forming cell, but not
      germinal center B cell, activity.
AB  - The low-affinity FcR for IgG FcgammaRIIB suppresses the development of IgG
      autoantibodies and autoimmune disease in normal individuals, but how this effect
      is mediated is incompletely understood. To investigate this issue, we created
      FcgammaRIIB-deficient versions of two previously described targeted BCR
      transgenic lines of mice that contain follicular B cells with specificity for the
      hapten arsonate, but with different levels of antinuclear autoantigen reactivity.
      The primary development and tolerance of both types of B cells were unaltered by
      the absence of FcgammaRIIB. Moreover, the reduced p-azophenylarsonate-driven
      germinal center and memory responses characteristic of the highly autoreactive
      clonotype were not reversed by an intrinsic FcgammaRIIB deficiency. In contrast,
      the p-azophenylarsonate-driven primary Ab-forming cell responses of both
      clonotypes were equivalently increased by such a deficiency. In total, our data
      do not support the idea that FcgammaRIIB directly participates in the action of
      primary or germinal center tolerance checkpoints. In contrast, this receptor
      apparently contributes to the prevention of autoimmunity by suppressing the
      production of autoreactive IgGs from B cells that have breached tolerance
      checkpoints and entered the Ab-forming cell pathway due to spontaneous, or cross
      reactive, Ag-mediated activation.

PMID- 17202352
TI  - Disruption of innate-mediated proinflammatory cytokine and reactive oxygen
      species third signal leads to antigen-specific hyporesponsiveness.
AB  - Successful Ag activation of naive T helper cells requires at least two signals
      consisting of TCR and CD28 on the T cell interacting with MHC II and CD80/CD86,
      respectively, on APCs. Recent evidence demonstrates that a third signal
      consisting of proinflammatory cytokines and reactive oxygen species (ROS)
      produced by the innate immune response is important in arming the adaptive immune
      response. In an effort to curtail the generation of an Ag-specific T cell
      response, we targeted the synthesis of innate immune response signals to generate
      Ag-specific hyporesponsiveness. We have reported that modulation of redox balance
      with a catalytic antioxidant effectively inhibited the generation of third signal
      components from the innate immune response (TNF-alpha, IL-1beta, ROS). In this
      study, we demonstrate that innate immune-derived signals are necessary for
      adaptive immune effector function and disruption of these signals with in vivo CA
      treatment conferred Ag-specific hyporesponsiveness in BALB/c, NOD, DO11.10, and
      BDC-2.5 mice after immunization. Modulating redox balance led to decreased Ag
      specific T cell proliferation and IFN-gamma synthesis by diminishing ROS
      production in the APC, which affected TNF-alpha levels produced by CD4(+) T cells
      and impairing effector function. These results demonstrate that altering redox
      status can be effective in T cell-mediated diseases such as autoimmune diabetes
      to generate Ag-specific immunosuppression because it inhibits the third signal
      necessary for CD4(+) T cells to transition from expansion to effector function.

PMID- 17202353
TI  - Involvement of regulatory T cells in the experimental autoimmune
      encephalomyelitis-preventive effect of dendritic cells expressing myelin
      oligodendrocyte glycoprotein plus TRAIL.
AB  - We previously reported the protection from myelin oligodendrocyte glycoprotein
      (MOG)-induced experimental autoimmune encephalomyelitis (EAE) by the adoptive
      transfer of genetically modified embryonic stem cell-derived dendritic cells (ES
      DC) presenting MOG peptide in the context of MHC class II molecules and
      simultaneously expressing TRAIL (ES-DC-TRAIL/MOG). In the present study, we found
      the severity of EAE induced by another myelin autoantigen, myelin basic protein,
      was also decreased after treatment with ES-DC-TRAIL/MOG. This preventive effect
      diminished, if the function of CD4(+)CD25(+) regulatory T cells (Treg) was
      abrogated by the injection of anti-CD25 mAb into mice before treatment with ES-DC
      TRAIL/MOG. The adoptive transfer of CD4(+)CD25(+) T cells from ES-DC-TRAIL/MOG
      treated mice protected the recipient mice from MOG- or myelin basic protein
      induced EAE. The number of Foxp3(+) cells increased in the spinal cords of mice
      treated with ES-DC-TRAIL/MOG. In vitro experiments showed that TRAIL expressed in
      genetically modified ES-DC and also in LPS-stimulated splenic macrophages had a
      capacity to augment the proliferation of CD4(+)CD25(+) T cells. These results
      suggest that the prevention of EAE by treatment with ES-DC-TRAIL/MOG is mediated,
      at least in part, by MOG-reactive CD4(+)CD25(+) Treg propagated by ES-DC
      TRAIL/MOG. For the treatment of organ-specific autoimmune diseases, induction of
      Treg reactive to the organ-specific autoantigens by the transfer of DC-presenting
      Ags and simultaneously overexpressing TRAIL therefore appears to be a promising
      strategy.

PMID- 17202354
TI  - Redundancy in B cell developmental pathways: c-Cbl inactivation rescues early B
      cell development through a B cell linker protein-independent pathway.
AB  - Deficiency in the adaptor protein B cell linker protein (BLNK) results in a
      substantial but incomplete block in B cell development, suggesting that
      alternative pathways exist for B lineage differentiation. Another adaptor
      protein, c-Cbl, plays a negative regulatory role in several BCR-signaling
      pathways. We therefore investigated the role of c-Cbl during B cell development
      and addressed the possibility that redundancies in pathways for B cell
      differentiation could be further revealed by eliminating negative effects
      mediated by c-Cbl. Strikingly, c-Cbl inactivation reversed a number of the
      critical defects in early B cell differentiation that are seen in BLNK-deficient
      mice. c-Cbl(-/-)BLNK(-/-) mice exhibited normalized down-regulation of pre-BCR
      and CD43, up-regulation of MHC class II, and augmented L chain rearrangement,
      resulting in a successful transition from pre-B cells to immature B cells. c-Cbl
      inactivation also reversed the potentially tumor-predisposing hyperproliferative
      response of BLNK(-/-) pre-B cells to IL-7. Pre-BCR cross-linking induced enhanced
      and prolonged tyrosine phosphorylation in c-Cbl(-/-)BLNK(-/-) pre-BCR(+) pre-B
      cells compared with c-Cbl(+/-)BLNK(-/-) cells, including elevated phosphorylation
      of Lyn, Syk, Btk, and phospholipase C-gamma2. Our studies suggest that some, but
      not all, pre-BCR-triggered developmental events can be mediated by BLNK
      independent pathways that are negatively regulated by c-Cbl, and further suggest
      that different events during early B cell development require different strength
      or duration of pre-BCR signaling.

PMID- 17202355
TI  - Cigarette smoke impairs NK cell-dependent tumor immune surveillance.
AB  - In this study, we investigated the impact of cigarette smoke on tumor immune
      surveillance and its consequences to lung tumor burden in a murine lung
      metastasis model. Cigarette smoke exposure significantly increased the numbers of
      lung metastases following B16-MO5 melanoma challenge. This effect was reversible;
      we observed significantly fewer tumor nodules following smoking cessation. Using
      RAG2(-/-) and RAG2(-/-)gamma(c)(-/-) mice, we provide strong evidence that
      increased tumor incidence was NK cell dependent. Furthermore, we show that
      cigarette smoke suppressed NK activation and attenuated NK CTL activity, without
      apparent effect on activating or inhibitory receptor expression. Finally,
      activation of NK cells through bone marrow-derived dendritic cells conferred
      protection against lung metastases in smoke-exposed mice; however, protection was
      not as efficacious as in sham-exposed mice. To our knowledge, this is the first
      experimental evidence showing that cigarette smoke impairs NK cell-dependent
      tumor immune surveillance and that altered immunity is associated with increased
      tumor burden. Our findings suggest that altered innate immunity may contribute to
      the increased risk of cancer in smokers.

PMID- 17202356
TI  - First glimpse of the peptide presentation by rhesus macaque MHC class I: crystal
      structures of Mamu-A*01 complexed with two immunogenic SIV epitopes and insights
      into CTL escape.
AB  - The infection of rhesus macaques (Macaca mulatta) by the SIV is the best animal
      model for studying HIV infection and for AIDS vaccine development. A prevalent
      MHC class I allele, Mamu-A*01, is known to correlate with containment of SIV,
      which has been extensively explored in studies of CTL-based vaccination concepts.
      We determined the crystal structures of Mamu-A*01 complexed with two
      immunodominant SIV epitopes: the nonamer CM9 of group-specific Ag (Gag, 181-189;
      CTPYDINQM) and the octamer TL8 of transcription activator (Tat, 28-35; TTPESANL).
      The overall structures of the two Mamu-A*01 complexes are similar to other MHC
      class I molecules. Both structures confirm the presence of an absolutely
      conserved proline anchor residue in the P3 position of the Ag, bound to a D
      pocket of the Mamu-A*01 H chain with optimal surface complementarity. Like other
      MHC/peptide complex structures, the P2 and C-terminal residues of the epitopes
      are also important for anchoring to the MHC molecule, whereas the middle residues
      form an arch and their side chains are directed into solvent. These two
      structures reveal details of how Mamu-A*01 interacts with two well-studied
      epitopes at the atomic level. We discuss the structural basis of CTL escape,
      based on molecular models made possible by these two structures. The results we
      present in this study are most relevant for the rational design of Mamu-A*01
      restricted CTL epitopes with improved binding, as a step toward development of
      AIDS vaccines.

PMID- 17202357
TI  - Bcl10/Malt1 signaling is essential for TCR-induced NF-kappaB activation in
      thymocytes but dispensable for positive or negative selection.
AB  - During T cell development in the thymus, high-affinity/avidity TCR engagement
      induces negative selection by apoptosis, while lower affinity/avidity TCR
      interactions lead to positive selection and survival of thymocytes. Yet, the
      mechanisms that discriminate between positive and negative selection are not
      fully understood. One major regulator of survival and apoptosis in lymphoid cells
      is the transcription factor NF-kappaB. Several reports have indicated key roles
      for NF-kappaB in positive and negative selection. In peripheral T cells, TCR
      ligation activates NF-kappaB through a selective pathway that involves protein
      kinase Ctheta, Bcl10, and Malt1. While protein kinase Ctheta is dispensable for
      thymic TCR signaling, the molecular roles of Bcl10 and Malt1 in thymocytes have
      not been investigated. In the present study, we show that both Bcl10 and Malt1
      are essential for TCR signaling in thymocytes as a genetic disruption of either
      molecule blocks TCR-induced NF-kappaB activation in these cells. To investigate
      the function of this pathway in thymic selection, we introduced the Bcl10 or
      Malt1 mutations into three well-established TCR transgenic mouse models.
      Surprisingly, using several in vivo or in vitro assays, we were unable to
      demonstrate a role for TCR-induced NF-kappaB activation in either positive or
      negative selection. Thus, while TCR signaling to NF-kappaB controls the
      activation of mature T cells, we suggest that this pathway is not involved in the
      positive or negative selection of thymocytes.

PMID- 17202358
TI  - Promoter region architecture and transcriptional regulation of the genes for the
      MHC class I-related chain A and B ligands of NKG2D.
AB  - Ligands of the NKG2D receptor, which activates NK cells and costimulates effector
      T cells, are inducibly expressed under harmful conditions, such as malignancies
      and microbial infections. Moreover, aberrant expression in autoimmune disease
      lesions may contribute to disease progression. Among these ligands are the
      closely related human MHC class I-related chains (MIC) A and B, which appear to
      be regulated by cellular stress. Analyses of MIC gene 5'-end flanking regions in
      epithelial tumor cells defined minimal core promoters that directed near maximum
      heat shock- or oxidative stress-induced transcriptional activation. Considerably
      larger fully functional promoters were required for maximum proliferation
      associated activation. These activities were dependent on core promoter sequences
      that included heat shock elements, which inducibly bound heat shock factor 1,
      TATA-like elements, and constitutively occupied Sp1 and inverted CCAAT box factor
      sites. By contrast, MIC gene activation by CMV infection was largely independent
      of these and upstream promoter sequences, and expression of viral immediate early
      gene (IE1 or IE2) products was sufficient for induction of transcription and
      surface protein expression. Altogether, these results reveal distinct modes of
      activation of the genes for the MIC ligands of NKG2D and provide a molecular
      framework for analyses of gene regulation under different cellular insult
      conditions.

PMID- 17202359
TI  - Age-associated defect in human TLR-1/2 function.
AB  - The effects of aging on human TLR function remain incompletely understood. We
      assessed TLR function and expression in peripheral blood monocytes from 159
      subjects in 2 age categories, 21-30 and >65 years of age, using a multivariable
      mixed effect model. Using flow cytometry to assess TLR-induced cytokine
      production, we observed a substantial, highly significant defect in TLR1/2
      induced TNF-alpha (p = 0.0003) and IL-6 (p < 0.0001) production, in older adults
      compared with young controls. In contrast to findings in aged mice, other TLR
      (including TLR2/6)-induced cytokine production appeared largely intact. These
      differences were highly significant even after correcting for covariates
      including gender, race, medications, and comorbidities. This defect in TLR1/2
      signaling may result from alterations in baseline TLR1 surface expression, which
      was decreased by 36% in older adults (p < 0.0001), whereas TLR2 surface
      expression was unaffected by aging. Production of IL-6 (p < 0.0001) and TNF-alpha
      (p = 0.003) after stimulation by N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2R,S)
      propyl]-Cys-[S]-Ser1-[S]-Lys(4) trihydrochloride was strongly associated with
      TLR1 surface expression. Diminished TLR1/2 signaling may contribute to the
      increased infection-related morbidity and mortality and the impaired vaccine
      responses observed in aging humans.

PMID- 17202360
TI  - CD27low CD4 T lymphocytes that accumulate in the mouse lungs during mycobacterial
      infection differentiate from CD27high precursors in situ, produce IFN-gamma, and
      protect the host against tuberculosis infection.
AB  - The generation of effector, IFN-gamma producing T lymphocytes and their
      accumulation at sites of infection are critical for host protection against
      various infectious diseases. The activation and differentiation of naive T
      lymphocytes into effector memory cells starts in lymphoid tissues, but it is not
      clear whether the Ag-experienced cells that leave lymph nodes (LN) are mature or
      if they undergo further changes in the periphery. We have previously shown that
      CD44(high)CD62L(low) effector CD4 T lymphocytes generated during the course of
      mycobacterial infection can be segregated into two subsets on the basis of CD27
      receptor expression. Only the CD27(low) subset exhibited a high capacity for IFN
      gamma secretion, indicating that low CD27 expression is characteristic of fully
      differentiated effector CD4 T lymphocytes. We demonstrate now that CD27(low) IFN
      gamma-producing CD4 T lymphocytes accumulate in the lungs but are rare in LNs.
      Several factors contribute to their preferential accumulation. First, CD27(low)
      CD4 T lymphocytes present in the LN are highly susceptible to apoptosis. Second,
      circulating CD27(low) CD4 T cells do not enter the LN but efficiently migrate to
      the lungs. Third, CD27(high) effector CD4 T cells that enter the lungs down
      regulate CD27 expression in situ. In genetically heterogeneous mice that exhibit
      varying susceptibility to tuberculosis, the accumulation of mature CD27(low) CD4
      T cells in the lungs correlates with the degree of protection against infection.
      Thus, we propose that terminal maturation of effector CD4 T lymphocytes in the
      periphery provides the host with efficient local defense and avoids potentially
      harmful actions of inflammatory cytokines in lymphoid organs.

PMID- 17202361
TI  - Identification of CXCL11 as a STAT3-dependent gene induced by IFN.
AB  - IFNs selectively regulate gene expression through several signaling pathways. The
      present study explored the involvement of STAT3 in the IFN-induced expression of
      the gene encoding the CXCL11 chemokine. The CXCL11 gene was induced in IFN
      sensitive Daudi cells, but not in an IFN-resistant DRST3 subline with a defective
      STAT3 signaling pathway. Although the IFN-stimulated gene ISG15 was induced to a
      similar extent in Daudi and DRST3 cells, expression of wild-type STAT3 in DRST3
      cells restored the IFN inducibility of CXCL11. Reconstitution of STAT3 knockout
      mouse embryonic fibroblasts with wild-type STAT3, or STAT3 with the canonical
      STAT3 dimerization site at Y705 mutated, restored IFN inducibility of the CXCL11
      gene. These data indicate that CXCL11 gene induction by IFN is STAT3 dependent,
      but that phosphorylation of Y705 of STAT3 is not required. Chromatin
      immunoprecipitation assays demonstrated that IFN treatment of Daudi and DRST3
      cells induced STAT3 binding to the CXCL11 promoter. Chromatin immunoprecipitation
      assays also revealed that NF-kappaB family member p65 and IFN regulatory factor
      (IRF)1 were bound to CXCL11 promoter upon IFN treatment of Daudi cells. In
      contrast, IFN induced the binding of p50 and IRF2 to the CXCL11 promoter in DRST3
      cells. The profile of promoter binding was indistinguishable in IFN-sensitive
      Daudi cells and DRST3 cells reconstituted with wild-type STAT3. Thus, STAT3 also
      plays a role in the recruitment of the transcriptional activators p65 and IRF1,
      and the displacement of the transcriptional repressors p50 and IRF2 from the
      CXCL11 promoter also appears to regulate the induction of CXCL11 gene
      transcription.

PMID- 17202362
TI  - Oxidized phospholipids inhibit phagocytosis and impair outcome in gram-negative
      sepsis in vivo.
AB  - Oxidized phospholipids that are generated during inflammation exert anti
      inflammatory properties and prevent death during murine endotoxemia. Oxidized 1
      palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) inhibits the
      interaction of LPS with LPS-binding protein and CD14. In this study, we
      determined the functional properties of OxPAPC and potential interference with
      CD14 during abdominal sepsis caused by Escherichia coli. Administration of OxPAPC
      rendered mice highly susceptible to E. coli peritonitis, as indicated by an
      accelerated mortality and enhanced bacterial outgrowth and dissemination. CD14(-/
      ) mice also displayed increased mortality and bacterial outgrowth and OxPAPC did
      not further impair host defense in these animals. The mechanisms by which OxPAPC
      and CD14 deficiency impaired the immune response differed: whereas CD14(-/-) mice
      demonstrated a strongly reduced recruitment of phagocytes to the site of the
      infection, OxPAPC did not influence the influx of inflammatory cells but strongly
      diminished the phagocytosing capacity of neutrophils and macrophages by a CD14
      independent mechanism. Furthermore, OxPAPC potently inhibited uptake of
      fluorospheres as well as receptor-mediated endocytosis and fluid-phase
      pinocytosis. These data suggest that oxidized phospholipids such as produced
      during inflammatory reactions may contribute to mortality during Gram-negative
      sepsis in vivo via impairment of the phagocytic properties of professional
      phagocytes.

PMID- 17202363
TI  - lgtC expression modulates resistance to C4b deposition on an invasive nontypeable
      Haemophilus influenzae.
AB  - We have previously shown that C3 binding to serum-resistant nontypeable
      Haemophilus influenzae (NTHi) strain R2866 is slower than C3 binding to a serum
      sensitive strain. Ab-dependent classical pathway activation is required for
      complement-dependent killing of NTHi. To further characterize the mechanism(s) of
      serum resistance of R2866, we compared binding of complement component C4b to
      R2866 with a serum-sensitive variant, R3392. We show that C4b binding to R2866
      relative to R3392 was delayed, suggesting regulation of the classical pathway of
      complement. Increased C4b deposition on R3392 was independent of the amount and
      subclass of Ab binding, suggesting that an impediment to C4b binding existed on
      R2866. Immunoblotting and mass spectrometry indicated that lipooligosaccharide
      and outer membrane proteins P2 and P5 were targets for C4b. P2 and P5 sequences
      and expression levels were similar in both strains. Insertional inactivation of
      the phase-variable lipooligosaccharide biosynthesis gene lgtC in R2866 augmented
      C4b deposition to levels seen with R3392 and rendered the bacteria sensitive to
      serum and whole blood. These results suggest a direct role of lgtC expression in
      the inhibition of C4b deposition and consequent serum resistance of R2866.
      Alteration of surface glycans of NTHi may be a critical event in determining the
      ability of a strain to evade host defenses and cause disseminated infection.

PMID- 17202364
TI  - Matrix metalloproteinase 9 activity enhances host susceptibility to pulmonary
      infection with type A and B strains of Francisella tularensis.
AB  - A striking feature of pulmonary infection with the Gram-negative intracellular
      bacterium Francisella tularensis, a category A biological threat agent, is an
      intense accumulation of inflammatory cells, particularly neutrophils and
      macrophages, at sites of bacterial replication. Given the essential role played
      by host matrix metalloproteinases (MMPs) in modulating leukocyte recruitment and
      the potentially indiscriminate destructive capacity of these cells, we
      investigated whether MMP-9, an important member of this protease family released
      by neutrophils and activated macrophages, plays a role in the pathogenesis of
      respiratory tularemia. We found that F. tularensis induced expression of MMP-9 in
      FVB/NJ mice and that the action of this protease is associated with higher
      bacterial burdens in pulmonary and extrapulmonary tissues, development of more
      extensive histopathology predominated by neutrophils, and increased morbidity and
      mortality compared with mice lacking MMP-9 (MMP-9(-/-)). Moreover, MMP-9(-/-)
      mice were able to resolve infection with either the virulence-attenuated type B
      (live vaccine strain) or the highly virulent type A (SchuS4) strain of F.
      tularensis. Disease resolution was accompanied by diminished leukocyte
      recruitment and reductions in both bacterial burden and proinflammatory cytokine
      production. Notably, neutrophilic infiltrates were significantly reduced in MMP
      9(-/-) mice, owing perhaps to limited release of Pro-Gly-Pro, a potent neutrophil
      chemotactic tripeptide released from extracellular matrix through the action of
      MMP-9. Collectively, these results suggest that MMP-9 activity plays a central
      role in modulating the clinical course and severity of respiratory tularemia and
      identifies MMPs as novel targets for therapeutic intervention as a means of
      modulating neutrophil recruitment.

PMID- 17202365
TI  - Targeted antireceptor therapy with monoclonal antibodies leads to the formation
      of inactivated tetrameric forms of ErbB receptors.
AB  - mAbs capable of disabling heterodimeric kinase complexes of the epidermal growth
      factor receptor (EGFR) and human EGFR type 2/neu have therapeutic relevance to
      various human cancers. In this study, we demonstrate that in addition to the
      dimer, EGFR and human EGFR type 2 can associate as homo- and heterotetramers. EGF
      induced phosphorylation of the tetramers was significantly lower than that of the
      dimers, indicating that the tetrameric receptor complexes have impaired signaling
      activity. Targeting v-erb-b2 erythroblastic leukemia viral oncogene homolog
      (erbB) receptors with mAbs promoted erbB tetrameric assembly, suggesting that a
      component of the antitumor activity may be mediated by the ability of Abs to
      shift the equilibrium from active dimeric to impaired tetrameric receptor complex
      states. This study suggests a novel therapeutic approach to disable signaling of
      erbB and potentially other receptors in tumors by biologic agents capable of
      inducing receptor tetramerization.

PMID- 17202366
TI  - Priming with cold-adapted influenza A does not prevent infection but elicits long
      lived protection against supralethal challenge with heterosubtypic virus.
AB  - We show in this study several novel features of T cell-based heterosubtypic
      immunity against the influenza A virus in mice. First, T cell-mediated
      heterosubtypic protection against lethal challenge can be generated by a very low
      priming dose. Second, it becomes effective within 5-6 days. Third, it provides
      protection against a very high dose challenge for >70 days. Also novel is the
      finding that strong, long-lasting, heterosubtypic protection can be elicited by
      priming with attenuated cold-adapted strains. We demonstrate that priming does
      not prevent infection of the lungs following challenge, but leads to earlier
      clearance of the virus and 100% survival after otherwise lethal challenge.
      Protection is dependent on CD8 T cells, and we show that CD4 and CD8 T cells
      reactive to conserved epitopes of the core proteins of the challenge virus are
      present after priming. Our results suggest that intranasal vaccination with cold
      adapted, attenuated live virus has the potential to provide effective emergency
      protection against emerging influenza strains for several months.

PMID- 17202367
TI  - Coordinated control of immunity to muscle stage Trichinella spiralis by IL-10,
      regulatory T cells, and TGF-beta.
AB  - We previously demonstrated that IL-10 is critical in the control of acute
      inflammation during development of Trichinella spiralis in the muscle. In this
      study, we use gene-targeted knockout mice, adoptive transfer of specific T cell
      populations, and in vivo Ab treatments to determine the mechanisms by which
      inflammation is controlled and effector T cell responses are moderated during
      muscle infection. We report that CD4(+)CD25(-) effector T cells, rather than
      CD4(+)CD25(+) regulatory T cells, suppress inflammation by an IL-10-dependent
      mechanism that limits IFN-gamma production and local inducible NO synthase
      induction. Conversely, we show that depletion of regulatory T cells during
      infection results in exaggerated Th2 responses. Finally, we provide evidence
      that, in the absence of IL-10, TGF-beta participates in control of local
      inflammation in infected muscle and promotes parasite survival.

PMID- 17202368
TI  - Distinct NKT cell subsets are induced by different Chlamydia species leading to
      differential adaptive immunity and host resistance to the infections.
AB  - We investigated the role of NKT cells in immunity to Chlamydia pneumoniae and
      Chlamydia muridarum infections using a combination of knockout mice and specific
      cellular activation approaches. The NKT-deficient mice showed exacerbated
      susceptibility to C. pneumoniae infection, but more resistance to C. muridarum
      infection. Activation of NKT reduced C. pneumoniae in vivo growth, but enhanced
      C. muridarum infection. Cellular analysis of invariant NKT cells revealed
      distinct cytokine patterns following C. pneumoniae and C. muridarum infections,
      i.e., predominant IFN-gamma in the former, while predominant IL-4 in the latter.
      The cytokine patterns of CD4(+) and CD8(+) T cells matched those of NKT cells.
      Our data provide in vivo evidence for a functionally diverse role of NKT cells in
      immune response to two intracellular bacterial pathogens. These results suggest
      that distinct NKT subsets are induced by even biologically closely related
      pathogens, thus leading to differential adaptive immune response and infection
      outcomes.

PMID- 17202369
TI  - Oral vaccination with salmonella simultaneously expressing Yersinia pestis F1 and
      V antigens protects against bubonic and pneumonic plague.
AB  - The gut provides a large area for immunization enabling the development of
      mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia
      pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and
      virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag
      expression was controlled under a promoter from the caf1 operon; two different
      promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in
      pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the
      best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated
      secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much
      greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V
      Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a
      single plasmid containing the caf1 operon and the chimeric promoter for V-Ag
      allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags
      elicited elevated Ab titers similar to their monotypic derivatives. For bubonic
      plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar
      efficacy (>83% survival) against approximately 1000 LD(50) Y. pestis. For
      pneumonic plague, immunized mice required immunity to both F1- and V-Ags because
      the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD(50) Y.
      pestis. These results show that a single Salmonella vaccine can deliver both F1-
      and V-Ags to effect both systemic and mucosal immune protection against Y.
      pestis.

PMID- 17202370
TI  - Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and
      Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4,
      TRIF, or TRAM.
AB  - The discovery that endosymbiotic Wolbachia bacteria play an important role in the
      pathophysiology of diseases caused by filarial nematodes, including lymphatic
      filariasis and onchocerciasis (river blindness) has transformed our approach to
      these disabling diseases. Because these parasites infect hundreds of millions of
      individuals worldwide, understanding host factors involved in the pathogenesis of
      filarial-induced diseases is paramount. However, the role of early innate
      responses to filarial and Wolbachia ligands in the development of filarial
      diseases has not been fully elucidated. To determine the role of TLRs, we used
      cell lines transfected with human TLRs and macrophages from TLR and adaptor
      molecule-deficient mice and evaluated macrophage recruitment in vivo. Extracts of
      Brugia malayi and Onchocerca volvulus, which contain Wolbachia, directly
      stimulated human embryonic kidney cells expressing TLR2, but not TLR3 or TLR4.
      Wolbachia containing filarial extracts stimulated cytokine production in
      macrophages from C57BL/6 and TLR4(-/-) mice, but not from TLR2(-/-) or TLR6(-/-)
      mice. Similarly, macrophages from mice deficient in adaptor molecules Toll/IL-1R
      domain-containing adaptor-inducing IFN-beta and Toll/IL-1R domain-containing
      adaptor-inducing IFN-beta-related adaptor molecule produced equivalent cytokines
      as wild-type cells, whereas responses were absent in macrophages from MyD88(-/-)
      and Toll/IL-1R domain-containing adaptor protein (TIRAP)/MyD88 adaptor-like (Mal)
      deficient mice. Isolated Wolbachia bacteria demonstrated similar TLR and adaptor
      molecule requirements. In vivo, macrophage migration to the cornea in response to
      filarial extracts containing Wolbachia was dependent on TLR2 but not TLR4. These
      results establish that the innate inflammatory pathways activated by
      endosymbiotic Wolbachia in B. malayi and O. volvulus filaria are dependent on
      TLR2-TLR6 interactions and are mediated by adaptor molecules MyD88 and TIRAP/Mal.

PMID- 17202371
TI  - Activation of the MAPK, ERK, following Leishmania amazonensis infection of
      macrophages.
AB  - IL-10 is a critical cytokine in determining host susceptibility to Leishmania
      spp. We previously demonstrated that macrophage-derived IL-10 could contribute to
      disease exacerbation, but the mechanisms whereby Leishmania infections led to IL
      10 induction were not fully understood. In this study, we demonstrated that
      infection of macrophages with Leishmania amazonensis amastigotes led to the
      activation of the MAPK, ERK1/2. This activation was required, but not sufficient
      for IL-10 induction. In addition to ERK activation, an inflammatory stimulus,
      such as low m.w. hyaluronic acid from the extracellular matrix, must also be
      present. The combination of these two signals resulted in the superinduction of
      IL-10. We also demonstrated that IgG on the surface of Leishmania amastigotes was
      required to achieve maximal IL-10 production from infected macrophages. Surface
      IgG engages macrophage FcgammaR to induce ERK activation. Macrophages lacking
      FcgammaR, or macrophages treated with an inhibitor of spleen tyrosine kinase, the
      tyrosine kinase that signals via FcgammaR, failed to activate ERK and
      consequently failed to produce IL-10 following infection with Leishmania
      amastigotes. We confirmed that ERK1/2 activation led to the phosphorylation of
      histone H3 at the IL-10 promoter, and this phosphorylation allowed for the
      binding of the transcription factor, Sp1, to the IL-10 promoter. Finally, the
      administration of U0126, an inhibitor of ERK activation, to infected mice
      resulted in decreased lesion progression with reduced numbers of parasites in
      them. Thus, our findings reveal an important role of MAPK, ERK signaling in the
      pathogenesis of Leishmania infection.

PMID- 17202372
TI  - Opsonization of HIV with complement enhances infection of dendritic cells and
      viral transfer to CD4 T cells in a CR3 and DC-SIGN-dependent manner.
AB  - In the present study, we demonstrated that opsonization of primary HIV-1 with
      human complement enhances infection of immature monocyte-derived dendritic cells
      (iDC) and transmission in trans of HIV to autologous CD4(+) T lymphocytes.
      Infection of iDC by opsonized primary R5- and X4-tropic HIV was increased 3- to 5
      fold as compared with infection by the corresponding unopsonized HIV. Enhancement
      of infection was dependent on CR3 as demonstrated by inhibition induced by
      blocking Abs. The interaction of HIV with CCR5 and CXCR4 on iDC was affected by
      opsonization. Indeed, stromal-derived factor-1 was more efficient in inhibiting
      infection of iDC with opsonized R5-tropic HIV-1(BaL) (45%) than with heat
      inactivated complement opsonized virus and similarly RANTES inhibited more
      efficiently infection of iDC with opsonized X4-tropic HIV-1(NDK) (42%) than with
      heat-inactivated complement opsonized virus. We also showed that attachment of
      complement-opsonized virus to DC-specific ICAM-grabbing nonintegrin (DC-SIGN)
      molecule on iDC and HeLa DC-SIGN(+) CR3(-) cells was 46% and 50% higher compared
      with heat-inactivated complement opsonized virus, respectively. Hence, Abs to DC
      SIGN suppressed up to 80% and 60% the binding of opsonized virus to HeLa cells
      and iDC, respectively. Furthermore, Abs to DC-SIGN inhibited up to 70% of the
      infection of iDC and up to 65% of infection in trans of autologous lymphocytes
      with opsonized virus. These results further demonstrated the role of DC-SIGN in
      complement opsonized virus uptake and infection. Thus, the virus uses complement
      to its advantage to facilitate early steps leading to infection following mucosal
      transmission of HIV.

PMID- 17202374
TI  - Vasoactive intestinal peptide balances pro- and anti-inflammatory cytokines in
      the Pseudomonas aeruginosa-infected cornea and protects against corneal
      perforation.
AB  - Corneal infection with Pseudomonas aeruginosa perforates the cornea in
      susceptible C57BL/6 (B6), but not resistant BALB/c, mice. To determine whether
      vasoactive intestinal peptide (VIP) played a role in development of the resistant
      response, protein expression levels were tested by immunocytochemistry and enzyme
      immunoassay in BALB/c and B6 corneas. Both mouse strains showed constitutive
      expression of corneal VIP protein and nerve fiber distribution. However,
      disparate expression patterns were detected in the cornea after infection. VIP
      protein was elevated significantly in BALB/c over B6 mice at 5 and 7 days
      postinfection. Therefore, B6 mice were injected with rVIP and subsequently
      demonstrated decreased corneal opacity and resistance to corneal perforation
      compared with PBS controls. rVIP- vs PBS-treated B6 mice also demonstrated down
      regulation of corneal mRNA and/or protein levels for proinflammatory
      cytokines/chemokines: IFN-gamma, IL-1beta, MIP-2, and TNF-alpha, whereas anti
      inflammatory mediators, IL-10 and TGF-beta1, were up-regulated. Treatment with
      rVIP decreased NO levels and polymorphonuclear neutrophil (PMN) number. To
      further define the role of VIP, peritoneal macrophages (Mphi) and PMN from BALB/c
      and B6 mice were stimulated with LPS and treated with rVIP. Treatment of LPS
      stimulated Mphi from both mouse strains resulted in decreased IL-1beta and MIP-2
      protein levels; PMN responded similarly. Both cell types also displayed a strain
      dependent differential response to rVIP, whereby B6 Mphi/PMN responded only to a
      higher concentration of VIP compared with cells from BALB/c mice. These data
      provide evidence that neuroimmune regulation of the cytokine network and host
      inflammatory cells functions to promote resistance against P. aeruginosa corneal
      infection.

PMID- 17202373
TI  - The mechanism underlying defective Fcgamma receptor-mediated phagocytosis by HIV
      1-infected human monocyte-derived macrophages.
AB  - Clearance of IgG-opsonized erythrocytes is impaired in HIV-1-infected patients,
      suggesting defective FcgammaR-mediated phagocytosis in vivo. We have previously
      shown defective FcgammaR-mediated phagocytosis in HIV-1-infected human monocyte
      derived macrophages (MDM), establishing an in vitro model for defective tissue
      macrophages. Inhibition was associated with decreased protein expression of FcR
      gamma-chain, which transduces immune receptor signals via ITAM motifs. FcgammaRI
      and FcgammaRIIIa signal via gamma-chain, whereas FcgammaRIIa does not. In this
      study, we showed that HIV-1 infection inhibited FcgammaRI-, but not FcgammaRIIa
      dependent Syk activation in MDM, showing that inhibition was specific for gamma
      chain-dependent signaling. HIV-1 infection did not impair gamma-chain mRNA levels
      measured by real-time PCR, suggesting a posttranscriptional mechanism of gamma
      chain depletion. HIV-1 infection did not affect gamma-chain degradation (n = 7, p
      = 0.94) measured in metabolic labeling/chase experiments, whereas gamma-chain
      biosynthesis was inhibited (n = 12, p = 0.0068). Using an enhanced GFP-expressing
      HIV-1 strain, we showed that FcgammaR-mediated phagocytosis inhibition is
      predominantly due to a bystander effect. Experiments in which MDM were infected
      in the presence of the antiretroviral drug 3TC suggest that active viral
      replication is required for inhibition of phagocytosis in MDM. These data suggest
      that HIV-1 infection may affect only gamma-chain-dependent FcgammaR functions,
      but that this is not restricted to HIV-1-infected cells.

PMID- 17202375
TI  - PDE4 inhibition prevents preterm delivery induced by an intrauterine
      inflammation.
AB  - The aim of this study was to explore the anti-inflammatory properties of
      phosphodiesterase-4 (PDE4) inhibitors in vivo and their potential ability to
      prevent inflammation-induced preterm delivery. Indeed, intrauterine inflammation
      is the major etiology of very preterm delivery, the leading cause of neonatal
      mortality and morbidity. Intrauterine injection of Escherichia coli LPS in 15-day
      pregnant mice induced an increase of PDE4 activity and PDE4B expression at the
      maternofetal interface, a rise of amniotic fluid levels of TNF-alpha, IL-1beta,
      IL-6, and IL-10 and provoked massive preterm delivery and fetal demise. Selective
      PDE4 inhibition by rolipram prevented the rise in the proinflammatory cytokines.
      Following the nuclear translocation of the transcription factor NFkappaB, as a
      marker of cellular activation after the inflammatory challenge, showed a time
      dependent sequential activation of the gestational tissues, from the uterine
      mesometrial to the fetal compartment, particularly in the glycogen-trophoblastic
      cells of the placenta. This activation was disrupted by PDE4 inhibition, and
      inflammation-induced preterm delivery and fetal demise were prevented. PDE4
      selective inhibitors may thus represent a novel effective treatment to delay
      inflammation-induced preterm delivery and to prevent adverse outcomes in infants.

PMID- 17202376
TI  - Identification of genes selectively regulated by IFNs in endothelial cells.
AB  - IFNs are highly pleiotropic cytokines also endowed with marked antiangiogenic
      activity. In this study, the mRNA expression profiles of endothelial cells (EC)
      exposed in vitro to IFN-alpha, IFN-beta, or IFN-gamma were determined. We found
      that in HUVEC as well as in other EC types 175 genes were up-regulated (>2-fold
      increase) by IFNs, including genes involved in the host response to RNA viruses,
      inflammation, and apoptosis. Interestingly, 41 genes showed a >5-fold higher
      induction by IFN-alpha in EC compared with human fibroblasts; among them, the
      gene encoding the angiostatic chemokine CXCL11 was selectively induced by IFN
      alpha in EC along with other genes associated with angiogenesis regulation,
      including CXCL10, TRAIL, and guanylate-binding protein 1. These transcriptional
      changes were confirmed and extended by quantitative PCR analysis and ELISA;
      whereas IFN-alpha and IFN-beta exerted virtually identical effects on
      transcriptome modulation, a differential gene regulation by type I and type II
      IFN emerged, especially as far as quantitative aspects were concerned. In vivo,
      IFN-alpha-producing tumors overexpressed murine CXCL10 and CXCL11, guanylate
      binding protein 1, and TRAIL, with evidence of CXCL11 production by tumor
      associated EC. Overall, these findings improve our understanding of the
      antiangiogenic effects of IFNs by showing that these cytokines trigger an
      antiangiogenic transcriptional program in EC. Moreover, we suggest that
      quantitative differences in the magnitude of the transcriptional activation of
      IFN-responsive genes could form the basis for cell-specific transcriptional
      signatures.

PMID- 17202377
TI  - CD99 is a key mediator of the transendothelial migration of neutrophils.
AB  - Transendothelial migration of leukocytes is a critical event for inflammation,
      but the molecular regulation of this event is only beginning to be understood.
      PECAM (CD31) is a major mediator of monocyte and neutrophil transmigration, and
      CD99 was recently defined as a second mediator of the transmigration of
      monocytes. Expression of CD99 on the surface of circulating polymorphonuclear
      cells (PMN) is low compared with expression of CD99 on monocytes or expression of
      PECAM on PMN. We demonstrate here that, despite low expression of CD99, Fab of
      Abs against CD99 blocked over 80% of human neutrophils from transmigrating across
      HUVEC monolayers in an in vitro model of inflammation. Blocking CD99 on either
      the neutrophil or endothelial cell side resulted in a quantitatively equivalent
      block, suggesting a homophilic interaction between CD99 on the neutrophil and
      CD99 on the endothelial cell. Blocking CD99 and PECAM together resulted in
      additive effects, suggesting the two molecules work at distinct steps. Confocal
      microscopy confirmed that CD99-blocked neutrophils lodged in endothelial cell
      junctions at locations distal to PECAM-blocked neutrophils. The CD99-blocked PMN
      exhibited dynamic lateral movement within endothelial cell junctions, indicating
      that only the diapedesis step was blocked by interference with CD99. Anti-CD99
      mAb also blocked PMN transmigration in a second in vitro model that incorporated
      shear stress. Taken together, the evidence demonstrates that PECAM and CD99
      regulate distinct, sequential steps in the transendothelial migration of
      neutrophils during inflammation.

PMID- 17202378
TI  - Lipopolysaccharide-induced up-regulation of triggering receptor expressed on
      myeloid cells-1 expression on macrophages is regulated by endogenous
      prostaglandin E2.
AB  - Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently
      identified cell surface molecule that is expressed by neutrophils and monocytes.
      TREM-1 expression is modulated by various ligands for TLRs in vitro and in vivo.
      However, the influence of PGE(2), a potential mediator of inflammation, on TREM-1
      expression has not been elucidated. In this study, we examined the effects of
      PGE(2) on LPS-induced TREM-1 expression by resident murine peritoneal macrophages
      (RPM) and human PBMC. PGE(2) significantly induced murine TREM-1 (mTREM-1)
      expression by RPM. Up-regulation of TREM-1 expression was specific to PGE(2)
      among arachidonic acid metabolites, while ligands for chemoattractant receptor
      homologous molecule expressed on Th2 cells and the thomboxane-like prostanoid
      receptor failed to induce mTREM-1 expression. PGE(2) also increased expression of
      the soluble form of TREM-1 by PBMC. LPS-induced TREM-1 expression was regulated
      by endogenous PGE(2) especially in late phase (>2 h after stimulation), because
      cyclooxygenase-1 and -2 inhibitors abolished this effect at that points. A
      synthetic EP4 agonist and 8-Br-cAMP also enhanced mTREM-1 expression by RPM.
      Furthermore, protein kinase A, PI3K, and p38 MAPK inhibitors prevented PGE(2)
      induced mTREM-1 expression by RPM. Activation of TREM-1 expressed on PGE(2)
      pretreated PBMC by an agonistic TREM-1 mAb significantly enhanced the production
      of IL-8 and TNF-alpha. These findings indicate that LPS-induced TREM-1 expression
      on macrophages is mediated, at least partly, by endogenous PGE(2) followed by EP4
      and cAMP, protein kinase A, p38 MAPK, and PI3K-mediated signaling. Regulation of
      TREM-1 and the soluble form of TREM-1 expression by PGE(2) may modulate the
      inflammatory response to microbial pathogens.

PMID- 17202379
TI  - IL-8 and IDO expression by human gingival fibroblasts via TLRs.
AB  - Human gingival fibroblasts (HGFs), a predominant cell type in tooth-supporting
      structure, are presently recognized for their active role in the innate immune
      response. They produce a variety of inflammatory cytokines in response to
      microbial components such as LPS from the key periodontal pathogen, Porphyromonas
      gingivalis. In this study, we demonstrated that HGFs expressed mRNA of TLRs 1, 2,
      3, 4, 5, 6, and 9, but not TLRs 7, 8, and 10. Stimulation of HGFs with highly
      purified TLR2 ligand (P. gingivalis LPS), TLR3 ligand (poly(I:C)), TLR4 ligand
      (Escherichia coli LPS), and TLR5 ligand (Salmonella typhimurium flagellin) led to
      expression of IL-8 and IDO. A potent TLR 9 ligand, CpG oligodeoxynucleotide 2006
      had no effect, although HGFs showed a detectable TLR9 mRNA expression. No
      significant enhancement on IL-8 or IDO expression was observed when HGFs were
      stimulated with various combinations of TLR ligands. Surprisingly, the TLR9
      ligand CpG oligodeoxynucleotide 2006 was able to specifically inhibit poly(I:C)
      induced IL-8 and IDO expression. TNF-alpha enhanced TLR ligand-induced IL-8
      production in HGFs, whereas IFN-gamma enhanced TLR ligand-induced IDO expression.
      HGF production of IDO in response to P. gingivalis LPS, IFN-gamma, or the two in
      combination inhibited T cell proliferation in MLRs. The observed T cell
      inhibition could be reversed by addition of either 1-methyl-dl-tryptophan or l
      tryptophan. Our results suggest an important role of HGFs not only in
      orchestrating the innate immune response, but also in dampening potentially
      harmful hyperactive inflammation in periodontal tissue.

PMID- 17202380
TI  - Human C-reactive protein protects mice from Streptococcus pneumoniae infection
      without binding to pneumococcal C-polysaccharide.
AB  - Human C-reactive protein (CRP) protects mice from lethality after infection with
      virulent Streptococcus pneumoniae type 3. For CRP-mediated protection, the
      complement system is required; however, the role of complement activation by CRP
      in the protection is not defined. Based on the in vitro properties of CRP, it has
      been assumed that protection of mice begins with the binding of CRP to
      pneumococcal C-polysaccharide on S. pneumoniae and subsequent activation of the
      mouse complement system. In this study, we explored the mechanism of CRP-mediated
      protection by utilizing two CRP mutants, F66A and F66A/E81A. Both mutants, unlike
      wild-type CRP, do not bind live virulent S. pneumoniae. We found that passively
      administered mutant CRP protected mice from infection as effectively as the wild
      type CRP did. Infected mice injected with wild-type CRP or with mutant CRP lived
      longer and had lower mortality than mice that did not receive CRP. Extended
      survival was caused by the persistence of reduced bacteremia in mice treated with
      any CRP. We conclude that the CRP-mediated decrease in bacteremia and the
      resulting protection of mice are independent of an interaction between CRP and
      the pathogen and therefore are independent of the ability of CRP to activate
      mouse complement. It has been shown previously that the Fcgamma receptors also do
      not contribute to such CRP-mediated protection. Combined data lead to the
      speculation that CRP acts on the effector cells of the immune system to enhance
      cell-mediated cytotoxicity and suggest investigation into the possibility of
      using CRP-loaded APC-based strategy to treat microbial infections.

PMID- 17202381
TI  - MyD88-dependent and MyD88-independent pathways in synergy, priming, and tolerance
      between TLR agonists.
AB  - TLRs sense components of microorganisms and are critical host mediators of
      inflammation during infection. Different TLR agonists can profoundly alter
      inflammatory effects of one another, and studies suggest that the sequence of
      exposure to TLR agonists may importantly impact on responses during infection. We
      tested the hypothesis that synergy, priming, and tolerance between TLR agonists
      follow a pattern that can be predicted based on differential engagement of the
      MyD88-dependent (D) and the MyD88-independent (I) intracellular signaling
      pathways. Inflammatory effects of combinations of D and I pathway agonists were
      quantified in vivo and in vitro. Experiments used several D-specific agonists, an
      I-specific agonist (poly(I:C)), and LPS, which acts through both the D and I
      pathways. D-specific agonists included: peptidoglycan-associated lipoprotein,
      Pam3Cys, flagellin, and CpG DNA, which act through TLR2 (peptidoglycan-associated
      lipoprotein and Pam3Cys), TLR5, and TLR9, respectively. D and I agonists were
      markedly synergistic in inducing cytokine production in vivo in mice. All of the
      D-specific agonists were synergistic with poly(I:C) in vitro in inducing TNF and
      IL-6 production by mouse bone marrow-derived macrophages. Pretreatment of bone
      marrow-derived macrophages with poly(I:C) led to a primed response to subsequent
      D-specific agonists and vice versa, as indicated by increased cytokine
      production, and increased NF-kappaB translocation. Pretreatment with a D-specific
      agonist augmented LPS-induced IFN-beta production. All D-specific agonists
      induced tolerance to one another. Thus, under the conditions studied here,
      simultaneous and sequential activation of both the D and I pathways causes
      synergy and priming, respectively, and tolerance is induced by agonists that act
      through the same pathway.

PMID- 17202382
TI  - IFN-gamma alters the response of Borrelia burgdorferi-activated endothelium to
      favor chronic inflammation.
AB  - Borrelia burgdorferi, the agent of Lyme disease, promotes proinflammatory changes
      in the endothelium that lead to the recruitment of leukocytes. The host immune
      response to infection results in increased levels of IFN-gamma in the serum and
      lesions of Lyme disease patients that correlate with greater severity of disease.
      Therefore, the effect of IFN-gamma on the gene expression profile of primary
      human endothelial cells exposed to B. burgdorferi was determined. B. burgdorferi
      and IFN-gamma synergistically augmented the expression of 34 genes, 7 of which
      encode chemokines. Six of these (CCL7, CCL8, CX3CL1, CXCL9, CXCL10, and CXCL11)
      attract T lymphocytes, and one (CXCL2) is specific for neutrophils. Synergistic
      production of the attractants for T cells was confirmed at the protein level. IL
      1beta, TNF-alpha, and LPS also cooperated with IFN-gamma to induce synergistic
      production of CXCL10 by the endothelium, indicating that IFN-gamma potentiates
      inflammation in concert with a variety of mediators. An in vitro model of the
      blood vessel wall revealed that an increased number of human T lymphocytes
      traversed the endothelium exposed to B. burgdorferi and IFN-gamma, as compared
      with unstimulated endothelial monolayers. In contrast, addition of IFN-gamma
      diminished the migration of neutrophils across the B. burgdorferi-activated
      endothelium. IFN-gamma thus alters gene expression by endothelia exposed to B.
      burgdorferi in a manner that promotes recruitment of T cells and suppresses that
      of neutrophils. This modulation may facilitate the development of chronic
      inflammatory lesions in Lyme disease.

PMID- 17202383
TI  - The postnatal maturation of the immunoglobulin heavy chain IgG repertoire in
      human preterm neonates is slower than in term neonates.
AB  - During the perinatal period the development of the IgH chain CDR3 (CDR-H3)
      repertoire of IgM transcripts is maturity-dependent and not influenced by
      premature exposure to Ag. To study whether maturity-dependent restrictions also
      predominate in the perinatal IgG repertoire we compared 1000 IgG transcripts from
      cord blood and venous blood of extremely preterm neonates (24-28 wk of gestation)
      and of term neonates from birth until early infancy with those of adults. We
      found the following. First, premature contact with the extrauterine environment
      induced the premature development of an IgG repertoire. However after preterm
      birth the diversification of the IgG repertoire was slower than that after term
      birth. Second, the IgG repertoire of preterm neonates retained immature
      characteristics such as short CDR-H3 regions and overrepresentation of D(H)7-27.
      Third, despite premature exposure to the extrauterine environment, somatic
      mutation frequency in IgG transcripts of preterm infants remained low until they
      reached a postconceptional age corresponding to the end of term gestation.
      Thereafter, somatic mutations accumulated with age at similar rates in preterm
      and term neonates and reached 30% of the adult level after 6 mo. In conclusion,
      class switch was inducible already at the beginning of the third trimester of
      gestation, but the developing IgG repertoire was characterized by similar
      restrictions as those of the developing IgM repertoire. Those B cells expressing
      more "mature" H chain sequences were not preferentially selected into the IgG
      repertoire. Therefore, the postnatal IgG repertoire of preterm infants until the
      expected date of delivery differs from the postnatal repertoire of term neonates.

PMID- 17202384
TI  - Functional analysis of birch pollen allergen Bet v 1-specific regulatory T cells.
AB  - Allergen-specific immunotherapy using peptides is an efficient treatment for
      allergic diseases. Recent studies suggest that the induction of CD4+ regulatory T
      (Treg) cells might be associated with the suppression of allergic responses in
      patients after allergen-specific immunotherapy. Our aim was to identify MHC class
      II promiscuous T cell epitopes for the birch pollen allergen Bet v 1 capable of
      stimulating Treg cells with the purpose of inhibiting allergic responses. Ag
      reactive CD4+ T cell clones were generated from patients with birch pollen
      allergy and healthy volunteers by in vitro vaccination of PBMC using Bet v 1
      synthetic peptides. Several CD4+ T cell clones were induced by using 2 synthetic
      peptides (Bet v 1(141-156) and Bet v 1(51-68)). Peptide-reactive CD4+ T cells
      recognized recombinant Bet v 1 protein, indicating that these peptides are
      produced by the MHC class II Ag processing pathway. Peptide Bet v 1(141-156)
      appears to be a highly MHC promiscuous epitope since T cell responses restricted
      by numerous MHC class II molecules (DR4, DR9, DR11, DR15, and DR53) were
      observed. Two of these clones functioned as typical Treg cells (expressed CD25,
      GITR, and Foxp3 and suppressed the proliferation and IL-2 secretion of other CD4+
      T cells). Notably, the suppressive activity of these Treg cells required cell
      cell contact and was not mediated through soluble IL-10 or TGF-beta. The
      identified promiscuous MHC class II epitope capable of inducing suppressive Treg
      responses may have important implication for the development of peptide-based Ag
      specific immunotherapy to birch pollen allergy.

PMID- 17202385
TI  - Monocyte-astrocyte networks regulate matrix metalloproteinase gene expression and
      secretion in central nervous system tuberculosis in vitro and in vivo.
AB  - CNS tuberculosis (CNS-TB) is the most deadly form of tuberculous disease
      accounting for 10% of clinical cases. CNS-TB is characterized by extensive tissue
      destruction, in which matrix metalloproteinases (MMPs) may play a critical role.
      We investigated the hypothesis that Mycobacterium tuberculosis activates monocyte
      astrocyte networks increasing the activity of key MMPs. We examined the
      expression of all human MMPs and the tissue inhibitors of metalloproteinases
      (TIMPs) in human astrocytes stimulated by conditioned medium from M. tuberculosis
      infected monocytes (CoMTB). Real-time RT-PCR showed that gene expression of MMP
      1, -2, -3, -7, and -9 was increased (p < 0.05). MMP-9 secretion was significantly
      up-regulated at 24 h and increased over 120 h (p < 0.01). MMP-1, -3, and -7
      secretion was not detected. Secretion of MMP-2 was constitutive and unaffected by
      CoMTB. Astrocyte gene expression and secretion of TIMP-1 was not affected by
      CoMTB although TIMP-2 secretion increased 3-fold at 120 h. Immunohistochemical
      analysis of human brain biopsies confirmed that astrocyte MMP-9 secretion is a
      predominant feature in CNS-TB in vivo. Dexamethasone inhibited astrocyte MMP-9,
      but not TIMP-1/2 secretion in response to CoMTB. CoMTB stimulated the nuclear
      translocation of NF-kappaB, inducing a 6-fold increase in nuclear p65 and a 2
      fold increase in nuclear p50. This was associated with degradation of
      IkappaBalpha and beta within 30 min, persisting for 24 h. In summary, networks
      active between monocytes and astrocytes regulate MMP-9 activity in tuberculosis
      and astrocytes are a major source of MMP-9 in CNS-TB. Astrocytes may contribute
      to a matrix degrading environment within the CNS and subsequent morbidity and
      mortality.

PMID- 17202386
TI  - A defect of regulatory T cells in patients with autoimmune polyendocrinopathy
      candidiasis-ectodermal dystrophy.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a
      monogenic recessive disease characterized by autoimmunity against multiple
      tissues, offers a unique possibility to study the breakdown of self-tolerance in
      humans. It is caused by mutations in the autoimmune regulator gene (AIRE), which
      encodes a transcriptional regulator. Work using Aire(-/-) mice suggests that Aire
      induces ectopic expression of peripheral Ags and promotes their presentation in
      the thymus. We have explored reasons for the difference between the comparatively
      mild phenotype of Aire-deficient mice and human APECED patients. We provide
      evidence that, unlike in the Aire(-/-) mice, in the patients a key mediator of
      active tolerance, the CD4(+)CD25(+) regulatory T (Treg) cell subset is impaired.
      This was shown by significantly decreased expression of FOXP3 mRNA and protein,
      decreased function, and alterations in TCR repertoire. Also, in the normal human
      thymus a concentric accumulation of AIRE(+) cells was seen around thymic
      Hassall's corpuscles, suggesting that in the patients these cells may be involved
      in the observed Treg cell failure. In Aire(-/-) mice the expression of FoxP3 was
      normal and even increased in target tissues in parallel with the lymphocyte
      infiltration process. Our results suggest that a Treg cell defect is involved in
      the pathogenesis of APECED and emphasize the importance of active tolerance
      mechanisms in preventing human autoimmunity.

PMID- 17202387
TI  - Direct interaction of surfactant protein A with myometrial binding sites:
      signaling and modulation by bacterial lipopolysaccharide.
AB  - Surfactant protein A (SFTPA1), a member of the collagenous lectin (collectin)
      family, was first described as a major constituent of lung surfactant, but has
      recently also been found in the female genital tract. Various microorganisms
      colonize this area and may cause intrauterine infection or trigger preterm labor.
      We found that SFTPA1 was not produced in the uterus. Instead, it was
      immunodetected transiently in rat myometrium at the end (Days 19 and 21) of
      gestation, but not postpartum, and in cultured myometrial cells. Fluorescence
      microscopy showed that Texas Red-labeled SFTPA1 bound to myometrial cells. This
      result was confirmed by biochemical approaches. [(125)I]-SFTPA1 bound to two
      myometrial cell proteins (55 and 210 kDa). This interaction was dependent on the
      integrity of the collagenlike domain of SFTPA1. SFTPA1 rapidly activated mitogen
      activated protein kinase 1/3 (MAPK1/3) in myometrial cells. Bacterial
      lipopolysaccharide (LPS), an agent known to trigger uterine contractions and
      preterm birth, also activated MAPK1/3. The prolonged treatment of myometrial
      cells with LPS or SFTPA1 upregulated PTGS2 (COX2) protein levels. The addition of
      rough-type LPS to SFTPA1 blocked the interaction of SFTPA1 with its binding sites
      and the activation of MAPK1/3 and PTGS2 by SFTPA1. Our data provide the first
      demonstration of a direct effect of SFTPA1 on rat myometrial cells and inhibitory
      cross talk between SFTPA1 and LPS signals, providing new insight into the
      mechanisms of normal and preterm parturition.

PMID- 17202388
TI  - Differential estradiol requirement for the induction of estrus behavior and the
      luteinizing hormone surge in two breeds of sheep.
AB  - For a better understanding of the mechanisms that lead to the preovulatory
      GnRH/LH surge and estrus behavior, the minimum estradiol (E) requirements (dose
      and duration) to induce each of these events were determined and compared between
      two breeds of ewes having either single (Ile de France) or multiple (Romanov)
      ovulations. The ewes were initially studied during a natural estrus cycle, and
      were then ovariectomized and run through successive artificial estrus cycles. For
      these artificial cycles the duration and amplitude of the follucular phase E
      increase were manipulated by E implants. Under all conditions, the onset of
      estrus behavior was similar in the two breeds, although its duration was longer
      in Romanov ewes. While a moderate E signal (6 cm for 12 h) induced an LH surge in
      10/10 Ile de France ewes, a larger E signal (12 cm for 12 h) was minimally
      effective in Romanov ewes (4/10). Additional studies revealed that a small E
      signal (3 cm for 6 h) induced full estrus behavior in all Romanov ewes but was
      completely ineffective in Ile de France animals (0/10). Higher doses and mostly
      longer durations of the E signal (12 cm for 24 h) were required to induce a surge
      in all the Romanov ewes. These results demonstrate a clear difference in the E
      requirement for the induction of estrus behavior and the LH surge between breeds
      of ewes that have different ovulation rates. These data provide compelling
      evidence that, in one breed, the neuronal systems that regulate both events
      require different estrogen signals.

PMID- 17202389
TI  - Evidence for the involvement of testicular protein CRISP2 in mouse sperm-egg
      fusion.
AB  - CRISP2, originally known as Tpx-1, is a cysteine-rich secretory protein
      specifically expressed in male haploid germ cells. Although likely to be involved
      in gamete interaction, evidence for a functional role of CRISP2 in fertilization
      still remains poor. In the present study, we used a mouse model to examine the
      subcellular localization of CRISP2 in sperm and its involvement in the different
      stages of fertilization. Results from indirect immunofluorescence and protein
      extraction experiments indicated that mouse CRISP2 is an intraacrosomal component
      that remains associated with sperm after capacitation and the acrosome reaction
      (AR). In vitro fertilization assays using zona pellucida-intact mouse eggs showed
      that an antibody against the protein significantly decreased the percentage of
      penetrated eggs, with a coincident accumulation of perivitelline sperm. The
      failure to inhibit zona pellucida penetration excludes a detrimental effect of
      the antibody on sperm motility or the AR, supporting a specific participation of
      CRISP2 at the sperm-egg fusion step. In agreement with this evidence, recombinant
      mouse CRISP2 (recCRISP2) specifically bound to the fusogenic area of mouse eggs,
      as previously reported for rat CRISP1, an epididymal protein involved in gamete
      fusion. In vitro competition investigations showed that incubation of mouse zona
      free eggs with a fixed concentration of recCRISP2 and increasing amounts of rat
      CRISP1 reduced the binding of recCRISP2 to the egg, suggesting that the proteins
      interact with common complementary sites on the egg surface. Our findings
      indicate that testicular CRISP2, as observed for epididymal CRISP1, is involved
      in sperm-egg fusion through its binding to complementary sites on the egg
      surface, supporting the idea of functional cooperation between homologous
      molecules to ensure the success of fertilization.

PMID- 17202391
TI  - Carcass traits and M. longissimus lumborum palatability attributes of calf- and
      yearling-finished steers.
AB  - A 2-yr experiment was conducted to compare carcass characteristics and meat
      palatability attributes of steers ((3/4) British, (1/4) Continental) finished
      postweaning as calves or yearlings. Calves and yearlings of the same contemporary
      group were designated to a finishing system at weaning. Calves (n = 73) were
      finished in the feedlot (191 d) on a high-concentrate diet. Yearlings (n = 84)
      grazed crop residues after weaning, followed by spring and summer pasture
      grazing, and concluded with a short finishing period (91 d) in the feedlot. All
      steers were fed to a constant, fat thickness endpoint of 1 cm. The M. longissimus
      lumborum steaks from each production system were aged for 7, 14, or 21 d for
      Warner-Bratzler shear force determination and for 7 or 14 d for in-house sensory
      panel evaluation. Insoluble, percent soluble, and total collagen were determined.
      Yearlings produced heavier (P < 0.001) carcasses with larger (P < 0.001) LM areas
      and lower (P < 0.001) marbling scores and quality grades. Calves possessed
      greater amounts of total collagen (P < 0.001), with a significantly greater
      percentage of soluble collagen compared with yearlings (39.72 vs. 24.38%). Calves
      produced steaks with lower (P < 0.001) shear force values and greater (P < 0.001)
      sensory ratings for flavor. The USDA Choice steaks from the calves were more (P <
      0.001) tender and more (P < 0.050) palatable than Choice steaks from yearlings,
      and USDA Select steaks from calves were rated more tender (P < 0.001), juicy (P =
      0.012), and desirable (P < 0.001) than Select steaks from yearlings. As expected,
      increasing aging time from 7- to 14- to 21-d produced steaks with lower (P <
      0.001) shear force values, regardless of the production system. Risk
      probabilities showed 1.24% of the steaks from calf-finished steers and 21.22% of
      steaks from yearling-finished steers to be tough. Sensory rating probabilities
      showed the steaks from the calves were most likely to be desirable for
      tenderness, whereas steaks from the yearlings were most likely to be undesirable
      for tenderness, juiciness, flavor, and overall acceptability. Thus, calf-finished
      steers produce carcasses superior in quality and palatability compared with those
      from yearling-finished steers. However, yearling-finished steers can produce
      tender beef with extended aging.

PMID- 17202390
TI  - Pregnancy in the brown Norway rat: a model for investigating the genetics of
      placentation.
AB  - The placenta facilitates the exchange of nutrients and wastes in an effort to
      promote fetal development. Disruptions in the establishment of the placenta and
      its interactions with the maternal uterus are potential causes of pregnancy
      failure. In this study we investigated the pregnancy phenotype of two inbred rat
      strains: the Dahl Salt Sensitive (DSS) strain and the Brown Norway (BN) strain.
      The DSS strain is reported to have large litters, whereas the BN strain has small
      litters. Pregnant female rats of each strain were killed on various days of
      gestation. At the time of killing, the number of viable versus dead and/or
      resorbing conceptuses was determined. Placental tissues from viable conceptuses
      were collected and processed for biochemical and histologic analyses. The number
      of viable conceptuses at Days 8.5 and 18.5 of gestation was significantly greater
      in DSS versus BN rats. Additionally, the number of resorbing and/or dying
      conceptuses was significantly greater in the BN strain than in the DSS strain.
      Maternal responses to pregnancy and elements of placental and fetal development
      in DSS and BN rats differed. Immunohistologic analysis of placentation and gene
      expression profiles revealed that trophoblast cell invasion into the uterine
      mesometrial compartment was significantly less in the BN strain versus the DSS
      strain. In contrast, the uterine natural killer cell population was reciprocally
      expanded in the BN strain. The impairment in trophoblast cell invasion in BN rats
      was associated with a smaller junctional zone compartment of the chorioallantoic
      placenta. Collectively, the data indicate that BN rats exhibit a unique form of
      placentation and may represent an excellent model for investigating the genetics
      of placental development.

PMID- 17202392
TI  - Salvage of blood urea nitrogen in sheep is highly dependent on plasma urea
      concentration and the efficiency of capture within the digestive tract.
AB  - The aims of this study were 1) to determine whether transfer of blood urea to the
      gastrointestinal tract (GIT) or the efficiency of capture of urea N within the
      GIT is more limiting for urea N salvage, and 2) to establish the relationship
      between plasma urea concentration and recycling of urea N to the GIT. We used an
      i.v. urea infusion model in sheep to elevate the urea entry rate and plasma
      concentrations, thus avoiding direct manipulation of the rumen environment that
      otherwise occurs when feeding additional N. Four growing sheep (28.1 +/- 0.6 kg
      of BW) were fed a low-protein (6.8% CP, DM basis) diet and assigned to 4 rates of
      i.v. urea infusion (0, 3.8, 7.5, or 11.3 g of urea N/d; 10-d periods) in a
      balanced 4 x 4 Latin square design. Nitrogen retention (d 6 to 9), urea
      kinetics([(15)N2]urea infusion over 80 h), and plasma AA were determined. Urea
      infusion increased apparent total tract digestibility of N (29.9 to 41.3%) and DM
      (47.5 to 58.9%), and N retention (1.45 to 5.46 g/d). The plasma urea N entry rate
      increased (5.1 to 21.8 g/d) with urea infusion, as did the amount of urea N
      entering the GIT (4.1 to 13.2 g/d). Urea N transfer to the GIT increased with
      plasma urea concentration, but the increases were smaller at greater
      concentrations of plasma urea. Anabolic use of urea N within the GIT also
      increased with urea infusion (1.43 to 2.98 g/d; P = 0.003), but anabolic use as a
      proportion of GIT entry was low and decreased (35 to 22%; P = 0.003) with urea
      infusions. Consequently, much (44 to 67%) of the urea N transferred to the GIT
      returned to the liver for resynthesis of urea (1.8 to 9.2 g/d; P < 0.05). The
      present results suggest that transfer of blood urea to the GIT is 1) highly
      related to blood urea concentration, and 2) less limiting for N retention than is
      the efficiency of capture of recycled urea N by microbes within the GIT.

PMID- 17202393
TI  - Effect of age, muscle type, and insulin-like growth factor-II genotype on muscle
      proteolytic and lipolytic enzyme activities in boars.
AB  - Recently, a paternally expressed quantitative trait nucleotide (QTN) in the
      regulatory sequence of the IGF-II gene with effects on muscle growth and fat
      deposition was discovered in the pig. This QTN is also known as the IGF-II
      intron3 G3072A mutation. The aim of the current study was to determine the
      effects of age, muscle type, and IGF-II genotype (Apat, mutant allele vs. Gpat,
      wild-type allele) on muscle proteolytic and lipolytic enzyme activities. At
      approximately 4, 8, 16, and 26 wk of age, boars (n = 6 to 15 per genotype x age
      group) were slaughtered and mu- and m-calpain (CALP), calpastatin (CAST),
      cathepsins (CATH) B+L and H, acid lipase, and phospholipase activities were
      measured in Longissimus thoracis et lumborum, Semimembranosus, and Triceps
      brachii muscle samples taken soon after slaughter. Activities of CATH B+L and H,
      mu- and m-CALP, and acid lipase were not affected by the IGF-II genotype.
      Activity of CAST was greater (P < 0.005) and m-CALP:CAST was less (P < 0.05) in
      Apat animals. Because CAST activity and m-CALP:CAST are known to be related to
      protein degradation, satellite cell fusion, or both, it is likely that
      differences in proteolytic enzyme activities are involved in the greater
      percentage of muscle mass in Apat animals. Age and muscle type influenced
      proteolytic and lipolytic enzyme activities (P < 0.05), except for mu- and m-CALP
      (no effect of muscle) and acid lipase (no effect of age). The same pattern in mu
      CALP, CAST, and m-CALP:CAST with age was found during growth for the 3 muscles,
      although clear differences (P < 0.05) between muscles existed. In general, and in
      agreement with previous reports, greater enzyme activities were found in the more
      oxidative Triceps brachii muscle compared with the other 2 muscles. A remarkable
      increase (P < 0.05) from 16 to 26 wk of age in mu-CALP, CAST, mu-CALP:CAST, and
      CATH H and a large decrease (P < 0.05) in acid phospholipase and m-CALP:CAST was
      found. For m-CALP and CATH B+L, a gradual decrease (P < 0.05) was found with age.
      Although age effects on enzyme activities could only partly be interpreted
      biologically in relation to the muscle growth rate, this study showed that
      proteolytic and lipolytic enzyme activities change during growth.

PMID- 17202394
TI  - Effects of intermittent suckling and creep feed intake on pig performance from
      birth to slaughter.
AB  - An experiment was conducted to determine if the improved creep feed intake
      observed during intermittent suckling (IS) is important for postweaning
      performance. Therefore, creep feed intake of litters was assessed, and within
      litters, eaters and noneaters were distinguished using chromic oxide as an
      indigestible marker. Batches of sows were suckled intermittently (IS, 7 batches;
      n = 31) or continuously (control, 7 batches; n = 31). In the IS group, litters
      were separated from the sow for a period of 12 h/d (0930 to 2130), beginning 11 d
      before weaning. Litters were weaned at 4 wk of age. Litters had free access to
      creep feed from 1 wk of age onward. Five days after weaning, the piglets were
      moved as a litter to weanling pens. At 8 wk of age, 2 barrows and 2 gilts were
      randomly chosen from each litter and moved to a finishing facility. Feed intake
      was improved by IS during the last 11 d of lactation (IS, 284 +/- 27 vs. control,
      83 +/- 28 g/piglet; P < 0.001) and after weaning during the first (IS, 201 +/- 24
      vs. control, 157 +/- 25 g x piglet(-1) x d(-1); P < 0.05) and second (IS, 667 +/-
      33 vs. control, 570 +/- 35 g x piglet(-1) x d(-1); P < 0.05) wk. Thereafter, no
      differences were found to slaughter. Weaning BW was lower in IS litters (IS, 7.1
      +/- 0.01 vs. control, 8.1 +/- 0.01 kg/piglet; P < 0.05), but 7 d after weaning BW
      was similar (IS, 8.5 +/- 0.2 vs. control, 8.7 +/- 0.2 kg/piglet; P = 0.18), and
      no differences were found to slaughter. The percentage of eaters within a litter
      was not increased by IS during lactation (IS, 23 +/- 4.5% vs. control, 19 +/-
      4.1%; P = 0.15). Weaning BW did not differ between eaters and noneaters (eater,
      7.7 +/- 0.1 vs. noneater, 7.5 +/- 0.08 kg/piglet; P = 0.63). From 1 until 4 wk
      after weaning, piglets that were eaters during lactation had heavier BW than
      noneaters (eater, 20.3 +/- 0.3 kg vs. noneater, 18.2 +/- 0.2 kg; P < 0.05). The
      influence of eating creep feed during lactation on BW and ADG and the influence
      of suckling treatment never showed an interaction. We conclude that IS increases
      ADFI during lactation on a litter level and improves ADG in the first week and
      ADFI in the first and second weeks after weaning. No long-term effects on ADFI or
      ADG were observed throughout the finishing period. In the current experiment, in
      which creep feed intake was low, the percentage of eaters within a litter was not
      increased, suggesting that creep feed intake of piglets that were already eating
      was stimulated by IS. Further, piglets that were eaters during lactation had
      heavier BW up to 4 wk after weaning.

PMID- 17202395
TI  - Effects of feeding Salmonella enterica serovar Typhimurium or serovar
      Choleraesuis on growth performance and circulating insulin-like growth factor-I,
      tumor necrosis factor-alpha, and interleukin-1beta in weaned pigs.
AB  - The most common Salmonella serovars causing clinical disease in pigs are
      Salmonella enterica serovars Typhimurium (Typhimurium) and Choleraesuis. Given
      that the swine host-adapted serovar Choleraesuis has been reported to cause
      systemic disease, a different disease outcome from that of Typhimurium, our
      working hypothesis was that this serovar would likely engage systemic immune
      inflammatory mechanisms, resulting in elevated systemic cytokine secretion. Forty
      eight weaned pigs were blocked by BW and sex, and randomly allotted to 1 of 3
      treatments in a 14-d study. Each treatment had 8 replicates (pens), with 2
      pigs/pen. The treatments consisted of a negative control and pigs repeatedly fed
      10(8) cfu of Typhimurium or Choleraesuis. On d 0, the pigs were fed Choleraesuis
      or Typhimurium in dough balls, and the bacteria were refed twice weekly
      throughout the experiment. Control pigs received dough balls without bacteria.
      All pigs were housed in temperature-controlled rooms under constant lighting and
      were fed a standard corn-soybean meal-based nursery diet. Pig BW and feed
      disappearance were used to determine ADG, ADFI, and G:F. Rectal temperatures were
      obtained daily from 1 pig/pen beginning 2 d before the first bacterial feeding
      through d 7 using rapid-response digital thermometers. Serum was collected on d
      0, 7, and 14 from a single pig/pen for analysis of IGF-I, tumor necrosis factor
      alpha , and IL-1beta. There was no change in the rectal temperature of the
      control or the Typhimurium-challenged pigs (compared with d 0) or when comparing
      Typhimurium-challenged pigs with control animals. In contrast, pigs fed
      Choleraesuis had increased rectal temperatures beginning on d 2 and continuing
      through d 7 (P < 0.05), with the greatest elevation on d 3 (P < 0.001) compared
      with the control pigs. Average daily gain and ADFI of pigs challenged with
      Typhimurium did not differ from those of the control animals. Pigs fed
      Choleraesuis had a 25% reduction in ADG (P < 0.0001) and ADFI (P < 0.002)
      compared with the control pigs. On d 7, pigs fed Choleraesuis had reduced serum
      IGF-I compared with control (P < 0.01) or Typhimurium-challenged pigs (P = 0.01).
      Bacterial feeding did not affect serum tumor necrosis factor-alpha or IL-1beta
      compared with control pigs at any time throughout the experiment. We conclude
      that repeated exposure of weaned pigs to Choleraesuis reduced growth performance
      in the absence of changes in systemic inflammatory cytokines.

PMID- 17202396
TI  - Technical note: how to use Winbugs to draw inferences in animal models.
AB  - This paper deals with Bayesian inferences of animal models using Gibbs sampling.
      First, we suggest a general and efficient method for updating additive genetic
      effects, in which the computational cost is independent of the pedigree depth and
      increases linearly only with the size of the pedigree. Second, we show how this
      approach can be used to draw inferences from a wide range of animal models using
      the computer package Winbugs. Finally, we illustrate the approach in a simulation
      study, in which the data are generated and analyzed using Winbugs according to a
      linear model with i.i.d errors having Student's t distributions. In conclusion,
      Winbugs can be used to make inferences in small-sized, quantitative, genetic data
      sets applying a wide range of animal models that are not yet standard in the
      animal breeding literature.

PMID- 17202398
TI  - The bovine dominant ovarian follicle.
AB  - Central roles in reproductive biology (i.e., growth and development of the
      oocyte, steroidogenesis, and ovulation) are played by the ovarian dominant
      follicle (DF). The DF is different from other follicles because it can escape
      atresia (the fate of all other follicles), and if exposed to the LH surge, its
      cells will differentiate into the corpus luteum. The DF was originally studied by
      looking at the surface of ovary through a surgical approach. Current studies
      employ a less-invasive ultrasound technique to track the growth and development
      of the DF. Recruitment and selection, the processes that give rise to the DF, and
      dominance, the physiological state of the mature DF, are important areas of basic
      research. Results of these basic studies are easily translated into real-world
      problems in farm animal reproduction. Superovulation, for example, overrides the
      selection mechanism and increases the number of ovulations. Understanding the
      factors that affect the size of the recruited pool should increase success rates
      (i.e., number of collected embryos) for superovulation. In most animals, the DF
      is short-lived, existing for long enough to allow for the final maturation of the
      oocyte. Some DF become atretic because they mature during the luteal phase and
      are never exposed to the LH surge. For other DF, the LH surge redirects the DF
      toward its ultimate demise (i.e., luteinization, ovulation, and differentiation
      into the corpus luteum). The DF is managed pharmacologically within protocols for
      timed AI. When timed AI fails, there may be abnormal corpus luteum development
      and early embryonic loss; outcomes that are secondary to inadequate follicular
      cell maturation and incomplete oocyte capacitation in the DF. Future work on the
      DF will clarify its underlying biological functions so that a variety of needs in
      farm animal reproduction can be efficiently managed.

PMID- 17202397
TI  - The halothane gene, energy metabolism, adenosine monophosphate-activated protein
      kinase, and glycolysis in postmortem pig longissimus dorsi muscle.
AB  - The presence of the halothane gene results in PSE meat. However, the exact
      mechanisms linking the halothane gene and the incidence of PSE meat remain
      unclear. We hypothesize that the presence of the halothane gene accelerates
      energy consumption in postmortem muscle, which activates adenosine monophosphate
      activated protein kinase (AMPK), leading to enhanced glycolysis and PSE meat. To
      test our hypothesis, energy status, AMPK activity, and glycolysis in the
      postmortem LM of the halothane gene carrier and halothane-negative pigs were
      compared. The results showed that the presence of the halothane gene accelerated
      energy depletion in postmortem muscle immediately after exsanguination, leading
      to rapid and early depletion of ATP, as shown by an increase in the (adenosine
      monophosphate + inosine monophosphate):ATP ratio in postmortem LM. In addition,
      an early AMPK activation was observed in LM from halothane carriers. The fructose
      2,6-diphosphate concentration in postmortem LM was well correlated with AMPK
      activation. To be a potent stimulator of phosphofructose kinase, the increase in
      fructose-2,6-diphosphate is expected to activate phosphofructose kinase, a key
      enzyme controlling glycolysis, leading to enhanced glycolysis and early
      accumulation of lactic acid. In summary, this study showed that the presence of
      the halothane gene induced early energy depletion, which could be a primary
      reason causing AMPK activation, leading to accelerated glycolysis and an
      increased incidence of PSE meat. However, AMPK might also be activated by other
      mechanisms besides energy depletion, which warrants further studies.

PMID- 17202399
TI  - Influence of body condition and bovine somatotropin on estrous behavior,
      reproductive performance, and concentrations of serum somatotropin and plasma
      fatty acids in postpartum Brahman-influenced cows.
AB  - Ninety-nine multiparous Brahman-influenced (1/4 to 3/8 Brahman) cows were managed
      to achieve low (BCS = 4.3 +/- 0.1; n = 50) or moderate (BCS = 6.1 +/- 0.1; n =
      49) body condition (BC) to determine the influence of bovine somatotropin (bST)
      on estrous characteristics, reproductive performance, and concentrations of serum
      GH and plasma NEFA. Beginning 32 d postpartum, cows within each BC were assigned
      randomly to treatment with or without bST. Non-bST-treated cows received no
      treatment, and treated cows were administered bST (Posilac, 500 mg s.c.) on d 
      35, -21, and -7 before initiation of the breeding season. On d -7, all cows
      received an intravaginal, controlled internal drug-releasing (CIDR) device. On d
      0 (initiation of the 70-d breeding season), the CIDR were removed and cows
      received prostaglandin F2alpha (PGF2alpha). Blood samples were collected from the
      median caudal vein of the cows at each bST treatment and at d -28 and 0. Estrous
      behavior was monitored by radiotelemetry during the first 30 d of the breeding
      season. Growth hormone was increased (P < 0.05) in low and moderate BC cows
      treated with bST. The percentage of cows detected in estrus during the first 30 d
      of the breeding season was decreased (P = 0.05) for low BC (64%) compared with
      moderate BC (82%) cows. The interval to first estrus tended (P = 0.07) to be
      shorter in low BC-bST-treated cows (3.7 +/- 1.9 d) than in moderate BC-bST
      treated cows (9.6 +/- 1.8 d). During the first 30 d of the breeding season, cows
      in low BC had a decreased (P = 0.02) number of mounts received and increased (P =
      0.001) quiescence between mounts compared with cows in moderate BC. The number of
      mounts received was reduced (P = 0.04) in bST-treated cows. More (P = 0.02) cows
      treated with bST became pregnant during the first 3 d of the breeding season
      compared with non-bST-treated cows. The cumulative first-service conception rate
      tended (P = 0.07) to be greater for bST-low BC cows than non-bST-treated cows in
      low or moderate BC. On d 0, NEFA were greater (P < 0.05) in bST-treated vs. non
      bST-treated cows. Low BC and bST reduced the intensity of behavioral estrus in
      postpartum Brahman-influenced cows. However, bST increased the first-service
      conception rate during the first 30 d of breeding and pregnancy rates during the
      first 3 d of breeding in postpartum Brahman-influenced cows.

PMID- 17202400
TI  - STI-571 (imatinib mesylate) enhances the apoptotic efficacy of pyrrolo-1,5
      benzoxazepine-6, a novel microtubule-targeting agent, in both STI-571-sensitive
      and -resistant Bcr-Abl-positive human chronic myeloid leukemia cells.
AB  - Interactions between the Bcr-Abl kinase inhibitor STI-571 (imatinib mesylate) and
      a novel microtubule-targeting agent (MTA), pyrrolo-1,5-benzoxazepine (PBOX)-6,
      were investigated in STI-571-sensitive and -resistant human chronic myeloid
      leukemia (CML) cells. Cotreatment of PBOX-6 with STI-571 induced significantly
      more apoptosis in Bcr-Abl-positive CML cell lines (K562 and LAMA-84) than either
      drug alone (P < 0.01). Cell cycle analysis of propidium iodide-stained cells
      showed that STI-571 significantly reduced PBOX-6-induced G2M arrest and polyploid
      formation with a concomitant increase in apoptosis. Similar results were obtained
      in K562 CML cells using lead MTAs (paclitaxel and nocodazole) in combination with
      STI-571. Potentiation of PBOX-6-induced apoptosis by STI-571 was specific to Bcr
      Abl-positive leukemia cells with no cytoxic effects observed on normal peripheral
      blood cells. The combined treatment of STI-571 and PBOX-6 was associated with the
      down-regulation of Bcr-Abl and repression of proteins involved in Bcr-Abl
      transformation, namely the antiapoptotic proteins Bcl-x(L) and Mcl-1.
      Importantly, PBOX-6/STI-571 combinations were also effective in STI-571-resistant
      cells. Together, these findings highlight the potential clinical benefits in
      simultaneously targeting the microtubules and the Bcr-Abl oncoprotein in STI-571
      sensitive and -resistant CML cells.

PMID- 17202401
TI  - A comparison between ranolazine and CVT-4325, a novel inhibitor of fatty acid
      oxidation, on cardiac metabolism and left ventricular function in rat isolated
      perfused heart during ischemia and reperfusion.
AB  - Inhibition of fatty acid oxidation has been reported to be cardioprotective
      against myocardial ischemic injury; however, recent studies have questioned
      whether the cardioprotection associated with putative fatty acid oxidation
      inhibitors, such as ranolazine and trimetazidine, are due to changes in substrate
      oxidation. Therefore, the goals of this study were to compare the effects of
      ranolazine with a new fatty acid oxidation inhibitor, CVT-4325 [(R)-1-(2
      methylbenzo[d]thiazol-5-yloxy)-3-(4-((5-(4-(trifluoromethyl)phenyl)-1,2,4
      oxadiazol-3-yl)methyl)-piperazin-1-yl)propan-2-ol], on carbohydrate and fatty
      acid oxidation and on left ventricular (LV) function in the response to
      ischemia/reperfusion in rat isolated perfused hearts. Metabolic fluxes were
      determined in hearts perfused in an isovolumic Langendorff mode using 13C nuclear
      magnetic resonance isotopomer analysis or in isolated working hearts using
      [14C]glucose and [3H]palmitate, with and without 10 microM ranolazine or 3 microM
      CVT-4325. Isovolumic perfused hearts were also subjected to 30 min of low-flow
      ischemia (0.3 ml/min) and 60 min of reperfusion, and working hearts were
      subjected to 15 min of zero-flow ischemia and 60 min of reperfusion. Regardless
      of the experimental protocol, ranolazine had no effect on carbohydrate or fatty
      acid oxidation, whereas CVT-4325 significantly reduced fatty acid oxidation up to
      approximately 7-fold with a concomitant increase in carbohydrate oxidation. At
      these same concentrations, although ranolazine significantly improved LV
      functional recovery following ischemia/reperfusion, CVT-4325 had no significant
      protective effect. These results demonstrate that at pharmacologically relevant
      concentrations, ischemic protection by ranolazine was not mediated by inhibition
      of fatty acid oxidation and conversely that inhibition of fatty acid oxidation
      with CVT-4325 was not associated with improved LV functional recovery.

PMID- 17202402
TI  - Base excision repair proteins are required for integrin-mediated suppression of
      bleomycin-induced DNA breakage in murine lung endothelial cells.
AB  - Engagement of integrin cell adhesion receptors suppresses bleomycin (BLM)-induced
      DNA strand breakage in endothelial cells. Previous investigation of cells from
      poly(ADP-ribose) polymerase (PARP)-1 knockout mice and with an inhibitor of the
      enzyme indicated that this facilitator of base excision repair (BER) is required
      for integrin-mediated suppression of DNA strand breakage. Here, small inhibitory
      RNA (siRNA) was used to assess the requirement for the BER proteins, DNA ligase
      III (Lig3) alpha, PARP-1, and X-ray repair complementing defective repair in
      Chinese hamster cells 1 (XRCC1), and for the long-patch BER ligase, DNA ligase I
      (Lig1), in integrin-mediated protection from BLM-induced DNA breakage. Murine
      lung endothelial cells (MLECs) were transfected with siRNA, treated with anti
      beta1 integrin antibody, and then BLM. 3'-OH in DNA and accumulation of
      phosphorylated histone H2AX (gammaH2AX), which reflects double-strand breakage,
      were measured. Integrin antibody inhibited the increases in 3'-OH caused by BLM
      in MLECs transfected with either control or Lig1 siRNA. However, after knockdown
      of Lig3alpha, PARP-1, or XRCC1, suppression of DNA breakage by integrin antibody
      was limited. BLM increased gammaH2AX levels, and integrin treatment inhibited
      this by 57 to 73% in MLECs transfected with control siRNA. Integrin engagement
      also inhibited increases in gammaH2AX in BLM-treated cells transfected with Lig1
      siRNA. In contrast, Lig3alpha, PARP-1, and XRCC1 siRNAs prevented integrin
      mediated inhibition of BLM-induced gammaH2AX levels. The results suggest that the
      BER proteins, Lig3alpha, PARP-1, and XRCC1, are required for integrin-mediated
      suppression of BLM-induced DNA breakage.

PMID- 17202403
TI  - Effects of the inducible nitric-oxide synthase inhibitor L-N(6)-(1-iminoethyl)
      lysine on microcirculation and reactive nitrogen species generation in the kidney
      following lipopolysaccharide administration in mice.
AB  - The mortality rate for septic patients with acute renal failure is approximately
      doubled compared with patients with sepsis alone. Unfortunately, the treatment
      for sepsis-induced renal failure has advanced little during the last several
      decades. Because sepsis is often caused by lipopolysaccharide (LPS), a mouse
      model of LPS challenge was used to study the development of kidney injury. We
      hypothesized that inducible nitric-oxide synthase (iNOS)-catalyzed nitric oxide
      production and that generation of reactive nitrogen species (RNS) might play a
      role in the microcirculatory defect and resulting tubular injury associated with
      LPS administration. Fluorescent intravital videomicroscopy was used to assess
      renal peritubular capillary perfusion and document RNS generation by renal
      tubules in real time. As early as 6 h after LPS administration (10 mg/kg i.p.),
      RNS generation (rhodamine fluorescence), redox stress [NAD(P)H autofluorescence],
      and the percentage of capillaries without flow were each significantly increased
      compared with saline-treated mice (p < 0.05). The generation of RNS was supported
      by the detection of nitrotyrosine-protein adducts in the kidney using
      immunohistochemistry. The iNOS inhibitor l-N(6)-(1-iminoethyl)-lysine (l-NIL; 3
      mg/kg i.p.) completely blocked the increase in rhodamine fluorescence and NAD(P)H
      autofluorescence and prevented the capillary defects at 6 h after LPS
      administration. These results suggest that iNOS-derived RNS is an important
      contributor to the peritubular capillary perfusion defects and RNS generation
      that occur during sepsis and emphasize that pharmacological inhibition of iNOS
      may provide beneficial effects during sepsis by improving renal capillary
      perfusion and reducing RNS generation in the kidney.

PMID- 17202404
TI  - Dominance of amyloid precursor protein sequence over host cell secretases in
      determining beta-amyloid profiles studies of interspecies variation and drug
      action by internally standardized immunoprecipitation/mass spectrometry.
AB  - beta-Amyloid peptides, tentatively regarded as the principal neurotoxins
      responsible for Alzheimer's Disease, make up a set of products that varies
      significantly among different biological systems. The full implications of this
      complexity and its variations have yet to be defined. In this work, Abeta peptide
      populations were extracted from animal brain tissue or cell-conditioned media,
      immunoprecipitated with specific antibodies, and analyzed by matrix-assisted
      laser desorption time-of-flight mass spectrometry. (15)N-Substituted Abeta
      internal standards were added to gauge variations in the profile of captured
      peptides. Results from a range of species, including guinea pig, dog, rabbit, and
      wild-type and transgenic mice, showed that the Abeta peptide population in each
      system was mainly determined by the species of origin of the amyloid precursor
      protein (APP) and not by the host tissue or cell line. The same method was used
      to gauge the effect on the Abeta peptide profile of an inhibitor of gamma
      secretase, one of the two proteinases that excises Abeta peptides from the
      precursor protein with different effects on specific peptides. Overall, the
      results demonstrate that the species of origin of the APP substrate dictates the
      outcome of APP processing to a greater extent than the origin of the processing
      enzymes, an important consideration in rationalizing the properties of different
      model systems.

PMID- 17202405
TI  - Effects of dose and session duration on cocaine self-administration in rats.
AB  - Previous studies showed that an extended 6-h session duration produced an
      increasing rate of cocaine self-administration in rats. The present study further
      investigated the effect of dose and session duration on cocaine self
      administration. Eight groups of rats (4 doses x 2 session durations) self
      administered one of four cocaine doses (0.25, 0.5, 1, and 2 mg/kg/injection) in
      either 1- or 6-h sessions under a fixed-ratio schedule. In another experiment,
      two other groups of rats self-administered 0.5 mg/kg/injection of cocaine in
      either 3- or 12-h sessions. Cocaine self-administration increased at all doses in
      6-h sessions but not in 1-h sessions. Cocaine intake (milligram/kilogram) reached
      an asymptote earlier at a higher dose, but the rate of responding increased
      faster when the dose was lower. In ShA rats, the cocaine dose-response function
      was higher in rats at the two higher unit doses than at the lower doses. Cocaine
      self-administration increased in 6- and 12-h sessions, but not in 1- and 3-h
      sessions. The increase in self-administration was faster and greater in 12-h
      sessions than 6-h sessions. The data suggest that cocaine self-administration
      increases at various doses with prolonged access and that an increase in the rate
      of responding is positively and inversely associated with session duration and
      unit dose, respectively. Results also imply that cocaine intake reaches a ceiling
      faster at high doses even under short session duration. Therefore, high doses or
      prolonged access to cocaine are more likely to result in a pattern of cocaine
      intake that reflects compulsive use.

PMID- 17202406
TI  - Loss of Vav2 proto-oncogene causes tachycardia and cardiovascular disease in
      mice.
AB  - The Vav family is a group of signal transduction molecules that activate Rho/Rac
      GTPases during cell signaling. Experiments using knockout mice have indicated
      that the three Vav proteins present in mammals (Vav1, Vav2, and Vav3) are
      essential for proper signaling responses in hematopoietic cells. However, Vav2
      and Vav3 are also highly expressed in nonhematopoietic tissues, suggesting that
      they may have additional functions outside blood cells. Here, we report that this
      is the case for Vav2, because the disruption of its locus in mice causes
      tachycardia, hypertension, and defects in the heart, arterial walls, and kidneys.
      We also provide physiological and pharmacological evidence demonstrating that the
      hypertensive condition of Vav2-deficient mice is due to a chronic stimulation of
      the renin/angiotensin II and sympathetic nervous systems. Together, these results
      indicate that Vav2 plays crucial roles in the maintenance of cardiovascular
      homeostasis in mice.

PMID- 17202407
TI  - An essential role for talin during alpha(M)beta(2)-mediated phagocytosis.
AB  - The cytoskeletal, actin-binding protein talin has been previously implicated in
      phagocytosis in Dictyostelium discoideum and mammalian phagocytes. However, its
      mechanism of action during internalization is not understood. Our data confirm
      that endogenous talin can occasionally be found at phagosomes forming around IgG-
      and C3bi-opsonized red blood cells in macrophages. Remarkably, talin knockdown
      specifically abrogates uptake through complement receptor 3 (CR3, CD11b/CD18,
      alpha(M)beta(2) integrin) and not through the Fc gamma receptor. We show that
      talin physically interacts with CR3/alpha(M)beta(2) and that this interaction
      involves the talin head domain and residues W747 and F754 in the beta(2) integrin
      cytoplasmic domain. The CR3/alpha(M)beta(2)-talin head interaction controls not
      only talin recruitment to forming phagosomes but also CR3/alpha(M)beta(2) binding
      activity, both in macrophages and transfected fibroblasts. However, the talin
      head domain alone cannot support phagocytosis. Our results establish for the
      first time at least two distinct roles for talin during CR3/alpha(M)beta(2)
      mediated phagocytosis, most noticeably activation of the CR3/alpha(M)beta(2)
      receptor and phagocytic uptake.

PMID- 17202408
TI  - Two regions of the tail are necessary for the isoform-specific functions of
      nonmuscle myosin IIB.
AB  - To function in the cell, nonmuscle myosin II molecules assemble into filaments
      through their C-terminal tails. Because myosin II isoforms most likely assemble
      into homo-filaments in vivo, it seems that some self-recognition mechanisms of
      individual myosin II isoforms should exist. Exogenous expression of myosin IIB
      rod fragment is thus expected to prevent the function of myosin IIB specifically.
      We expected to reveal some self-recognition sites of myosin IIB from the
      phenotype by expressing appropriate myosin IIB rod fragments. We expressed the C
      terminal 305-residue rod fragment of the myosin IIB heavy chain (BRF305) in MRC-5
      SV1 TG1 cells. As a result, unstable morphology was observed like MHC-IIB(-/-)
      fibroblasts. This phenotype was not observed in cells expressing BRF305 mutants:
      1) with a defect in assembling, 2) lacking N-terminal 57 residues (N-57), or 3)
      lacking C-terminal 63 residues (C-63). A myosin IIA rod fragment ARF296
      corresponding to BRF305 was not effective. However, the chimeric ARF296, in which
      the N-57 and C-63 of BRF305 were substituted for the corresponding regions of
      ARF296, acquired the ability to induce unstable morphology. We propose that the N
      57 and C-63 of BRF305 are involved in self-recognition when myosin IIB molecules
      assemble into homo-filament.

PMID- 17202409
TI  - Function of the Caenorhabditis elegans ABC transporter PGP-2 in the biogenesis of
      a lysosome-related fat storage organelle.
AB  - Caenorhabditis elegans gut granules are intestine specific lysosome-related
      organelles with birefringent and autofluorescent contents. We identified pgp-2,
      which encodes an ABC transporter, in screens for genes required for the proper
      formation of gut granules. pgp-2(-) embryos mislocalize birefringent material
      into the intestinal lumen and are lacking in acidified intestinal V-ATPase
      containing compartments. Adults without pgp-2(+) function similarly lack
      organelles with gut granule characteristics. These cellular phenotypes indicate
      that pgp-2(-) animals are defective in gut granule biogenesis. Double mutant
      analysis suggests that pgp-2(+) functions in parallel with the AP-3 adaptor
      complex during gut granule formation. We find that pgp-2 is expressed in the
      intestine where it functions in gut granule biogenesis and that PGP-2 localizes
      to the gut granule membrane. These results support a direct role of an ABC
      transporter in regulating lysosome biogenesis. Previously, pgp-2(+) activity has
      been shown to be necessary for the accumulation of Nile Red-stained fat in C.
      elegans. We show that gut granules are sites of fat storage in C. elegans embryos
      and adults. Notably, levels of triacylglycerides are relatively normal in animals
      defective in the formation of gut granules. Our results provide an explanation
      for the loss of Nile Red-stained fat in pgp-2(-) animals as well as insight into
      the specialized function of this lysosome-related organelle.

PMID- 17202412
TI  - Endothelin B receptor blockade accelerates disease progression in a murine model
      of autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic
      disease that causes kidney failure and accounts for 10% of all patients who are
      on renal replacement therapy. However, the marked phenotypic variation between
      patients who carry the same PKD1 or PKD2 mutation suggests that nonallelic
      factors may have a greater influence on the cystic phenotype. Endothelin-1 (ET-1)
      transgenic mice have been reported to develop profound renal cystic disease and
      interstitial fibrosis without hypertension. The hypothesis that ET-1 acts as a
      modifying factor for cystic disease progression was tested in an orthologous
      mouse model of ADPKD (Pkd2(WS25/-)). Four experimental groups (n = 8 to 11) were
      treated from 5 to 16 wk of age with the highly selective orally active receptor
      antagonists ABT-627 (ETA) and A-192621 (ETB) singly or in combination.
      Unexpected, ETB blockade led to accelerated cystic kidney disease. Of
      significance, this was associated with a reduction in urine volume and sodium
      excretion and increases in urine osmolarity and renal cAMP and ET-1
      concentrations. The deleterious effect of chronic ETB blockade was neutralized by
      simultaneous ETA blockade. ETA blockade alone resulted in a significant increase
      in tubular cell proliferation but did not alter the cystic phenotype. It is
      concluded that the balance between ETA and ETB signaling is critical for
      maintaining tubular structure and function in the cystic kidney. These results
      implicate ET, acting via vasopressin-dependent and independent pathways, as a
      major modifying factor for cystic disease progression in human ADPKD.

PMID- 17202410
TI  - Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal
      muscle cells.
AB  - Ghrelin is an acylated peptidyl gastric hormone acting on the pituitary and
      hypothalamus to stimulate appetite, adiposity, and growth hormone release,
      through activation of growth hormone secretagogue receptor (GHSR)-1a receptor.
      Moreover, ghrelin features several activities such as inhibition of apoptosis,
      regulation of differentiation, and stimulation or inhibition of proliferation of
      several cell types. Ghrelin acylation is absolutely required for both GHSR-1a
      binding and its central endocrine activities. However, the unacylated ghrelin
      form, des-acyl ghrelin, which does not bind GHSR-1a and is devoid of any
      endocrine activity, is far more abundant than ghrelin in plasma, and it shares
      with ghrelin some of its cellular activities. In here we show that both ghrelin
      and des-acyl ghrelin stimulate proliferating C2C12 skeletal myoblasts to
      differentiate and to fuse into multinucleated myotubes in vitro through
      activation of p38. Consistently, both ghrelin and des-acyl ghrelin inhibit C2C12
      proliferation in growth medium. Moreover, the ectopic expression of ghrelin in
      C2C12 enhances differentiation and fusion of these myoblasts in differentiation
      medium. Finally, we show that C2C12 cells do not express GHSR-1a, but they do
      contain a common high-affinity binding site recognized by both acylated and des
      acylated ghrelin, suggesting that the described activities on C2C12 are likely
      mediated by this novel, yet unidentified receptor for both ghrelin forms.

PMID- 17202411
TI  - Adipocyte enhancer-binding protein-1 promotes macrophage inflammatory
      responsiveness by up-regulating NF-kappaB via IkappaBalpha negative regulation.
AB  - Nuclear factor kappaB (NF-kappaB) subunits comprise a family of eukaryotic
      transcription factors that are critically involved in cell proliferation,
      inflammation, and apoptosis. Under basal conditions, NF-kappaB subunits are kept
      under inhibitory regulation by physical interaction with NF-kappaB inhibitors
      (IkappaB subunits) in the cytosol. Upon stimulation, IkappaB subunits become
      phosphorylated, ubiquitinated, and subsequently degraded, allowing NF-kappaB
      subunits to translocate to the nucleus and bind as dimers to kappaB responsive
      elements of target genes. Previously, we have shown that AEBP1 enhances
      macrophage inflammatory responsiveness by inducing the expression of various
      proinflammatory mediators. Herein, we provide evidence suggesting that AEBP1
      manifests its proinflammatory function by up-regulating NF-kappaB activity via
      hampering IkappaBalpha, but not IkappaBbeta, inhibitory function through protein
      protein interaction mediated by the discoidin-like domain (DLD) of AEBP1. Such
      interaction renders IkappaBalpha susceptible to enhanced phosphorylation and
      degradation, subsequently leading to augmented NF-kappaB activity. Collectively,
      we propose a novel molecular mechanism whereby NF-kappaB activity is modulated by
      means of protein-protein interaction involving AEBP1 and IkappaBalpha. Moreover,
      our study provides a plausible mechanism explaining the differential regulatory
      functions exhibited by IkappaBalpha and IkappaBbeta in various cell types. We
      speculate that AEBP1 may serve as a potential therapeutic target for the
      treatment of various chronic inflammatory diseases and cancer.

PMID- 17202413
TI  - Overexpression of cyclooxygenase-2 predisposes to podocyte injury.
AB  - Increased podocyte cyclooxygenase-2 (COX-2) expression is seen in rats after
      renal ablation and Thy-1 nephritis and in cultured murine podocytes in response
      to mechanical stress. For investigation of whether COX-2 overexpression plays a
      role in podocyte injury, transgenic B6/D2 mice in which COX-2 expression was
      driven by a nephrin promoter were established. Selective upregulation of COX-2
      expression in podocytes of transgenic mouse kidneys was confirmed by
      immunoblotting and immunohistochemistry. Whether upregulation of podocyte
      specific COX-2 expression enhanced sensitivity to the development of Adriamycin
      nephropathy was examined. Adriamycin administration induced dramatically more
      albuminuria and foot process effacement and reduced glomerular nephrin mRNA and
      immunoreactivity in transgenic mice compared with wild-type littermates.
      Adriamycin also markedly increased immunoreactive COX-2 expression in podocytes
      from transgenic mice compared with the wild-type mice. Reverse transcriptase-PCR
      indicated that this increase represented a stimulation of endogenous COX-2 mRNA
      expression rather than COX-2 mRNA driven by the nephrin promoter. Balb/C mice,
      which are susceptible to renal injury by Adriamycin, also increased podocyte COX
      2 expression and reduced nephrin expression in response to administration of the
      drug. Long-term treatment with the COX-2-specific inhibitor SC58236 ameliorated
      the albuminuria that was induced by Adriamycin in the transgenic mice. SC58236
      also reduced Adriamycin-induced foot process effacement in both the COX-2
      transgenic mice and Balb/C mice. Therefore, overexpression of COX-2 may
      predispose podocytes to further injury.

PMID- 17202414
TI  - Advanced oxidation protein products accelerate renal fibrosis in a remnant kidney
      model.
AB  - Accumulation of plasma advanced oxidation protein products (AOPP) has been found
      in patients with chronic kidney disease. However, the biologic consequences of
      AOPP consumption on progression of renal disease still are unclear. For testing
      of the hypothesis that AOPP accelerate progression of chronic kidney disease,
      Sprague-Dawley rats were subjected to five-sixths nephrectomy (5/6 Nx) or to sham
      operation. Rats in each group were randomly assigned in three subgroups (n = 30
      in each group) and treated with repeated intravenous injections of AOPP-modified
      rat serum albumin (RSA), unmodified RSA, or vehicle for indicated period.
      Compared with RSA- or vehicle-treated 5/6 Nx rats, AOPP RSA-treated 5/6 Nx rats
      displayed greater proteinuria, higher serum creatinine, and lower creatinine
      clearance. AOPP challenge resulted in more renal hypertrophy, higher macrophage
      influx, and greater renal fibrosis in the remnant kidney. Chronic administration
      of AOPP in sham-operated rats increased urinary protein excretion and renal
      macrophage infiltration, but histologic renal fibrosis was not observed during
      the study period. AOPP treatment enhanced AOPP level in renal tissue. This was
      associated with marked increase of thiobarbituric acid reactive substances,
      decrease of glutathione peroxidase activity, and upregulated expression of
      monocyte chemoattractant protein-1 and TGF-beta1 in renal cortex. These data
      indicate that AOPP might be a new and potentially important mediator of renal
      fibrosis in the remnant kidney. Chronic accumulation of AOPP promotes renal
      fibrosis probably via a redox-sensitive inflammatory pathway.

PMID- 17202415
TI  - Downregulation of renal sodium transporters and tonicity-responsive enhancer
      binding protein by long-term treatment with cyclosporin A.
AB  - Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional
      activator that is regulated by ambient tonicity. TonEBP protects the renal
      medulla from the deleterious effects of hyperosmolality and regulates the urinary
      concentration by stimulating aquaporin-2 and urea transporters. The therapeutic
      use of cyclosporin A (CsA) is limited by nephrotoxicity that is manifested by
      reduced GFR, fibrosis, and tubular defects, including reduced urinary
      concentration. It was reported recently that long-term CsA treatment was
      associated with decreased renal expression of TonEBP target genes, including
      aquaporin-2, urea transporter, and aldose reductase. This study tested the
      hypothesis that long-term CsA treatment reduces the salinity/tonicity of the
      renal medullary interstitium as a result of inhibition of active sodium
      transporters, leading to downregulation of TonEBP. CsA treatment for 7 d did not
      affect TonEBP or renal function. Whereas expression of sodium transporters was
      altered, the medullary tonicity seemed unchanged. Conversely, 28 d of CsA
      treatment led to downregulation of TonEBP and overt nephrotoxicity. The
      downregulation of TonEBP involved reduced expression, cytoplasmic shift, and
      reduced transcription of its target genes. This was associated with reduced
      expression of active sodium transporters-sodium/potassium/chloride transporter
      type 2 (NKCC2), sodium/chloride transporter, and Na(+),K(+)-ATPase-along with
      increased sodium excretion and reduced urinary concentration. Infusion of
      vasopressin restored the expression of NKCC2 in the outer medulla as well as the
      expression and the activity of TonEBP. It is concluded that the downregulation of
      TonEBP in the setting of long-term CsA administration is secondary to the reduced
      tonicity of the renal medullary interstitium.

PMID- 17202416
TI  - A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and
      tubular cell apoptosis.
AB  - Renal fibrosis and tubular apoptosis are common mechanisms of progressive kidney
      disease. In vitro studies have implicated the c-Jun amino-terminal kinase (JNK)
      pathway in these processes. Both of the major JNK isoforms, JNK1 and JNK2, are
      expressed in the kidney, but their relative contribution to JNK signaling is
      unknown. This study investigated the role of JNK signaling in renal fibrosis and
      tubular apoptosis in the unilateral ureteral obstruction model using two
      different approaches: (1) Mice that were deficient in either JNK1 or JNK2 and (2)
      a specific inhibitor of all JNK isoforms, CC-401. Western blotting and
      immunostaining identified a marked increase in JNK signaling in the obstructed
      kidney, with substantial redundancy between JNK1 and JNK2 isoforms.
      Administration of CC-401 blocked JNK signaling in the rat obstructed kidney and
      significantly inhibited renal fibrosis in terms of interstitial myofibroblast
      accumulation and collagen IV deposition. This effect was attributed to
      suppression of gene transcription for the profibrotic molecules TGF-beta1 and
      connective tissue growth factor. CC-401 treatment also significantly reduced
      tubular apoptosis in the obstructed kidney. Genetic deletion of JNK1 or JNK2 did
      not protect mice from renal fibrosis in the unilateral ureteral obstruction
      model, but JNK1 deletion did result in a significant reduction in tubular cell
      apoptosis. In conclusion, this is the first study to demonstrate that JNK
      signaling plays a pathogenic role in renal fibrosis and tubular apoptosis.
      Furthermore, JNK1 plays a nonredundant role in tubular cell apoptosis. These
      studies identify the JNK pathway as a potential therapeutic target in progressive
      kidney disease.

PMID- 17202417
TI  - Mineral metabolism and arterial functions in end-stage renal disease: potential
      role of 25-hydroxyvitamin D deficiency.
AB  - In ESRD, arterial function is abnormal, characterized by decreased capacitive
      function (arterial stiffening) and reduced conduit function, shown by diminished
      flow-mediated dilation (FMD). The pathophysiology of these abnormalities is not
      clear, and this cross-sectional study analyzed possible relationships among
      arterial alterations and cardiovascular risk factors, including mineral
      metabolism parameters, such as serum parathormone, and vitamin D "nutritional"
      and "hormonal" status by measuring serum 25-hydroxyvitamin D [25(OH)D(3)] and
      1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] levels. Aortic stiffness (pulse wave
      velocity), brachial artery (BA) distensibility (echotracking; n = 42), BA FMD
      (hand-warming; n = 37), and arterial calcification scores (echography and plain x
      rays) were measured in 52 stable and uncomplicated patients who were on
      hemodialysis. 25(OH)D(3) and 1,25(OH)(2)D(3) serum levels were low and weakly
      correlated (r = 0.365, P < 0.05). After adjustment for BP and age, multivariate
      analyses indicated that 25(OH)D(3) and 1,25(OH)(2)D(3) were negatively correlated
      with aortic pulse wave velocity (P < 0.001) and positively correlated with BA
      distensibility (P < 0.01) and FMD (P < 0.001). Arterial calcification scores were
      not independently associated with 25(OH)D(3) and 1,25(OH)(2)D(3) serum
      concentrations. These results suggest that nutritional vitamin D deficiency and
      low 1,25(OH)(2)D(3) could be associated with arteriosclerosis and endothelial
      dysfunction in patients who have ESRD and are on hemodialysis.

PMID- 17202418
TI  - Molecular mechanisms of cyclosporin A inhibition of the cytokine-induced matrix
      metalloproteinase-9 in glomerular mesangial cells.
AB  - The effects of the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506)
      on the IL-1beta-induced matrix metalloproteinase-9 (MMP-9) were investigated.
      Impairment of the protease-antiprotease balance contributes to renal fibrosis,
      which is observed collectively under long-term treatment with either
      immunosuppressant. It is demonstrated that CsA, in contrast to FK506, reduced the
      IL-1beta-induced MMP-9 content in conditioned media of mesangial cells, which
      coincides with a reduction in the cytokine-induced MMP-9 mRNA level. Similar to
      FK506, the VIVIT peptide, a specific inhibitor of the nuclear factor of activated
      T cells, did not affect the cytokine-induced MMP-9 level. Moreover, CsA caused a
      dose-dependent inhibition on the IL-1beta-induced luciferase activity of a 1.3-kb
      MMP-9 promoter fragment. Concomitant, electrophoretic mobility shift assay
      revealed that CsA selectively inhibits the cytokine-induced DNA binding of
      activator protein-1 and NF-kappaB. The effects on NF-kappaB binding were
      accompanied by a marked reduction in the nuclear content of the p65 subunit of NF
      kappaB. Accordingly, CsA specifically impaired the IL-1beta-triggered degradation
      of inhibitory NF-kappaB. The suppressive effects by CsA on MMP-9 expression were
      accompanied by a reduction in the cytokine-induced phosphorylation of p42/p44 and
      c-Jun N-terminal Kinase (JNK). It is interesting that only the JNK inhibitor
      SP600125 impaired the cytokine-triggered MMP-9 level, suggesting that CsA, via
      inhibition of the JNK pathway, negatively interferes with the NF-kappaB-dependent
      transcriptional control of MMP-9. Interference with MMP-9 transcription may
      account for the accumulation of extracellular matrix underlying the high fibrotic
      potential of CsA during anti-inflammatory therapies with calcineurin inhibitors.

PMID- 17202419
TI  - Pkd2+/- vascular smooth muscles develop exaggerated vasocontraction in response
      to phenylephrine stimulation.
AB  - Vascular complications are the leading cause of morbidity and mortality in
      autosomal dominant polycystic kidney disease. Although evidence suggests an
      abnormal vascular reactivity, contractile function in Pkd mutant vessels has not
      been studied previously. Contractile response to phenylephrine (PE; 10(-10) to
      10(-4)M), an alpha1-adrenergic receptor agonist, was examined. De-endothelialized
      Pkd2(+/-) aortic rings generated a higher maximum force (F(max)) than that in
      wild-type (wt; 5.78 +/- 0.73 versus 2.69 +/- 0.43 mN; P < 0.001) and a
      significant left shift in PE dosage-response curve. On simultaneous recordings,
      Pkd2(+/-) aortic helical strips also responded to PE with a greater F(max) but a
      lesser [Ca(2+)](i) rise, resulting in a greatly enhanced Deltaforce/DeltaCa(2+)
      ratio than that in wt. At F(max), a higher elevation in the phosphorylated
      regulatory myosin light chain was observed in Pkd2(+/-) strips. Ca(2+)-dependent
      calmodulin/myosin light-chain kinase-mediated contraction was examined by direct
      Ca(2+) (pCa8-5) stimulation to beta-escin permeabilized aortic strips; the pCa
      force curve in Pkd2(+/-) strips was not shifted, thereby indicating that PE
      induced dosage-response alteration that resulted from Ca(2+)-independent
      mechanisms. Quantitative analyses of contractile proteins demonstrated elevated
      expressions in smooth muscle alpha-actin and myosin heavy chain in Pkd2(+/-)
      arteries, changes that likely contribute to the higher F(max). Similar to those
      in aortas, de-endothelialized Pkd2(+/-) resistance (fourth-order mesenteric)
      arteries responded to PE with a stronger contraction but a lesser [Ca(2+)](i)
      rise than in wt. Taken together, the arterial vasculature in Pkd2(+/-) mice
      exhibits an exaggerated contractile response and increased sensitivity to PE. An
      enhanced Ca(2+)-independent force generation and elevated contractile protein
      expression likely contribute to these abnormalities.

PMID- 17202421
TI  - Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion
      injury in vivo: role for xanthine oxidoreductase.
AB  - In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in
      hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action
      of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase
      (XOR). Herein, is investigated the effects of topical sodium nitrite
      administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats
      were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in
      the absence or presence of sodium nitrite (30 nmol) administered topically 1 min
      before reperfusion. Serum creatinine, serum aspartate aminotransferase,
      creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate
      concentrations were measured. The nitrite-derived NO-generating capacity of renal
      tissue was determined under acidic and hypoxic conditions by ozone
      chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia
      only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and
      injury, an effect that was abolished by previous treatment of rats with the NO
      scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5
      mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before
      reperfusion). Renal tissue homogenates produced significant amounts of NO from
      nitrite, an effect that was attenuated significantly by the xanthine
      oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate
      that topically administered sodium nitrite protects the rat kidney against I/R
      injury and dysfunction in vivo via the generation, in part, of xanthine
      oxidoreductase-catalyzed NO production. These observations suggest that nitrite
      therapy might prove beneficial in protecting kidney function and integrity during
      periods of I/R such as those encountered in renal transplantation.

PMID- 17202420
TI  - Diabetic endothelial nitric oxide synthase knockout mice develop advanced
      diabetic nephropathy.
AB  - The pathogenesis of diabetic nephropathy remains poorly defined, and animal
      models that represent the human disease have been lacking. It was demonstrated
      recently that the severe endothelial dysfunction that accompanies a diabetic
      state may cause an uncoupling of the vascular endothelial growth factor (VEGF)
      endothelial nitric oxide (eNO) axis, resulting in increased levels of VEGF and
      excessive endothelial cell proliferation. It was hypothesized further that VEGF
      NO uncoupling could be a major contributory mechanism that leads to diabetic
      vasculopathy. For testing of this hypothesis, diabetes was induced in eNO
      synthase knockout mice (eNOS KO) and C57BL6 controls. Diabetic eNOS KO mice
      developed hypertension, albuminuria, and renal insufficiency with arteriolar
      hyalinosis, mesangial matrix expansion, mesangiolysis with microaneurysms, and
      Kimmelstiel-Wilson nodules. Glomerular and peritubular capillaries were increased
      with endothelial proliferation and VEGF expression. Diabetic eNOS KO mice showed
      increased mortality at 5 mo. All of the functional and histologic changes were
      improved with insulin therapy. Inhibition of eNO predisposes mice to classic
      diabetic nephropathy. The mechanism likely is due to VEGF-NO uncoupling with
      excessive endothelial cell proliferation coupled with altered autoregulation
      consequent to the development of preglomerular arteriolar disease. Endothelial
      dysfunction in human diabetes is common, secondary to effects of glucose,
      advanced glycation end products, C-reactive protein, uric acid, and oxidants. It
      was postulated that endothelial dysfunction should predict nephropathy and that
      correction of the dysfunction may prevent these important complications.

PMID- 17202422
TI  - Identification of a unique transgenic mouse line that develops megabladder,
      obstructive uropathy, and renal dysfunction.
AB  - Urinary tract malformations, obstructive uropathy, and hypoplasia/dysplasia are
      extremely important in terms of pediatric health care costs, with end-stage renal
      failure in children estimated to cost >$15 billion annually in the United States
      alone. Even so, little is known regarding the mechanisms that control these
      processes. Identified was a unique mutant mouse model that develops in utero
      megabladder, resulting in variable hydroureteronephrosis and chronic renal
      failure secondary to obstructive uropathy. These animals, designated mgb for
      megabladder, possess a primary defect in bladder smooth muscle development that
      is apparent by embryonic day 15. The mgb mouse represents an excellent model for
      the study of normal and pathogenic bladder development, including the postnatal
      progression of chronic renal failure that results from the development of in
      utero obstructive uropathy.

PMID- 17202423
TI  - Local shear stress and brachial artery functions in end-stage renal disease.
AB  - Physiologic laminar shear stress (SS) is crucial for normal vascular structure
      and function. As a result of anemia-related lower whole-blood viscosity (WBV), SS
      could be reduced in patients with ESRD and might be associated with arterial
      functional alterations. In 44 patients with ESRD and 25 control subjects,
      brachial artery (BA) compliance and BA diameter changes (flow-mediated dilation
      [FMD[) were evaluated in response to local shear rate and SS changes during hand
      warming-induced hyperemia. Patients with ESRD and control subjects had similar BA
      blood flow, but SS was lower in patients with ESRD (P < 0.001), with lower shear
      rate (P < 0.01) and lower WBV (P < 0.0001). In control subjects, SS was
      positively (and physiologically) correlated with arterial diameter (P < 0.001).
      In contrast, in patients with ESRD, larger arterial diameter was associated with
      low SS (P < 0.05) and increased arterial wall elastic modulus (P < 0.001). Anemia
      associated low WBV aggravates low shear rate, further contributing to SS
      reduction. These abnormalities were associated with decreased vasodilating
      response to endothelial mechanical stimulation. Compared with control subjects,
      BA compliance and FMD increases in response to hand warming-induced increased SS
      were lower in ESRD patients (P < 0.01), whereas their BA diameter response to
      glyceryl trinitrate did not differ. The long-term WBV and SS increases after
      anemia correction improved FMD (P < 0.01) and BA compliance (P < 0.05) and
      heightened arterial wall sensitivity to mechanical stimulation. Maintenance low
      SS as a result of anemia could play an indirect role in arterial dysfunction in
      patients with ESRD.

PMID- 17202424
TI  - Tubular epithelial cell dedifferentiation is driven by the helix-loop-helix
      transcriptional inhibitor Id1.
AB  - In the fibrotic kidney, tubular cells undergo epithelial-to-mesenchymal
      transition (EMT), a phenotypic conversion that is characterized by sequential
      loss of epithelial markers and gain of mesenchymal features. For understanding of
      the molecular mechanism that governs this process, a high-throughput gene
      expression microarray analysis was used to identify the critical genes in the
      initial phase of the TGF-beta1-mediated EMT. Inhibitor of differentiation-1
      (Id1), a dominant negative antagonist of the basic helix-loop-helix transcription
      factors, was found to be induced rapidly in human proximal tubular epithelial
      cells after TGF-beta1 treatment. This induction of Id1 depended on intracellular
      Smad signaling. Ectopic expression of Id1 suppressed epithelial E-cadherin and
      zonula occludens-1 expression. Id1 physically formed complex with basic helix
      loop-helix transcription factor HEB (Hela E-box binding factor), sequestered its
      ability to bind to E-box, and repressed the trans-activation of E-cadherin
      promoter. However, overexpression of Id1 failed to induce alpha-smooth muscle
      actin, matrix metalloproteinase-2, fibronectin, and integrin-linked kinase (ILK),
      indicating its inability to confer a complete EMT. Overexpression of ILK or
      inhibition of ILK activity had no effect on Id1 induction by TGF-beta1,
      suggesting that Id1 and ILK have independent roles in epithelial
      dedifferentiation and EMT. In vivo, Id1 was induced exclusively in the
      degenerated, dilated renal tubular epithelium after unilateral ureteral
      obstruction. These studies identify Id1 transcriptional inhibitor as a crucial
      player in mediating cell dedifferentiation of renal tubular epithelium and
      suggest that EMT is a multistep process in which loss of epithelial adhesion does
      not necessarily lead to an autonomous mesenchymal transition.

PMID- 17202425
TI  - Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid
      antagonists on hippocampal long-term potentiation.
AB  - Memory deficits produced by marijuana arise partly via interaction of the
      psychoactive component, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), with
      cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce
      glutamate release and block hippocampal long-term potentiation (LTP), a potential
      substrate for learning and memory, the consequences of prolonged exposure to
      Delta(9)-THC for hippocampal function are poorly understood. Rats were injected
      with Delta(9)-THC (10 mg/kg, i.p., q.d.) for 1, 3, or 7 d, and
      electrophysiological recordings were performed in hippocampal slices 1d after the
      final injection. At this time, Delta(9)-THC was undetectable in hippocampus using
      liquid chromatography-mass spectrometry (LC-MS). Hippocampal LTP generated using
      high-frequency (HFS) or theta burst stimulation was not observed in brain slices
      from the 7-d Delta(9)-THC-treated animals. Delta(9)-THC also blocked HFS-LTP
      after 3 d, but not 1 d of treatment. The complete blockade of LTP persisted for 3
      d after the last Delta(9)-THC injection, and full reversal of the LTP deficit was
      not observed up to 14 d following Delta(9)-THC withdrawal. The cannabinoid
      antagonist AM251 (2 mg/kg), administered before each Delta(9)-THC injection
      prevented the blockade of LTP, and 7-d treatment with AM251 alone significantly
      increased the level of LTP. Chronic Delta(9)-THC also produced tolerance to the
      inhibition of synaptic GABA, but not glutamate release by the agonist WIN55,212
      2. These data define consequences of repeated Delta(9)-THC exposure for synaptic
      plasticity in the hippocampus that may help explain memory impairments in humans
      following chronic marijuana use.

PMID- 17202427
TI  - Orphanin FQ/nociceptin interacts with the basolateral amygdala noradrenergic
      system in memory consolidation.
AB  - Extensive evidence indicates that the basolateral complex of the amygdala (BLA)
      mediates hormonal and neurotransmitter effects on the consolidation of
      emotionally influenced memory and that such modulatory influences involve
      noradrenergic activation of the BLA. As the BLA also expresses a high density of
      receptors for orphanin FQ/nociceptin (OFQ/N), an opioid-like peptide with
      anxiolytic and amnestic properties, the present experiments investigated whether
      the BLA is involved in mediating OFQ/N effects on memory consolidation and
      whether such effects require noradrenergic activity. OFQ/N (0.01-100 pmol in 0.2
      microL) administered bilaterally into the BLA of male Sprague-Dawley rats
      immediately after aversively motivated inhibitory avoidance training induced dose
      dependent impairment on a 48-h retention trial. The beta(1)-adrenoceptor
      antagonist atenolol (2.0 nmol) administered concurrently into the BLA potentiated
      the dose-response effects of OFQ/N. In contrast, immediate post-training
      infusions of the peptidergic OFQ/N receptor antagonist [Nphe(1)]nociceptin(1
      13)NH(2) (1-100 pmol in 0.2 microL) into the BLA enhanced 48-h retention of
      inhibitory avoidance training, an effect that was blocked by coadministration of
      atenolol. Delayed infusions of OFQ/N or [Nphe(1)]nociceptin(1-13)NH(2) into the
      BLA administered either 6 or 3 h after training, respectively, or immediate post
      training infusions of OFQ/N into the adjacent central amygdala did not
      significantly alter retention performance. These findings indicate that
      endogenously released OFQ/N interacts with noradrenergic activity within the BLA
      in modulating memory consolidation.

PMID- 17202426
TI  - Associative representational plasticity in the auditory cortex: a synthesis of
      two disciplines.
AB  - Historically, sensory systems have been largely ignored as potential loci of
      information storage in the neurobiology of learning and memory. They continued to
      be relegated to the role of "sensory analyzers" despite consistent findings of
      associatively induced enhancement of responses in primary sensory cortices to
      behaviorally important signal stimuli, such as conditioned stimuli (CS), during
      classical conditioning. This disregard may have been promoted by the fact that
      the brain was interrogated using only one or two stimuli, e.g., a CS(+) sometimes
      with a CS(-), providing little insight into the specificity of neural plasticity.
      This review describes a novel approach that synthesizes the basic experimental
      designs of the experimental psychology of learning with that of sensory
      neurophysiology. By probing the brain with a large stimulus set before and after
      learning, this unified method has revealed that associative processes produce
      highly specific changes in the receptive fields of cells in the primary auditory
      cortex (A1). This associative representational plasticity (ARP) selectively
      facilitates responses to tonal CSs at the expense of other frequencies, producing
      tuning shifts toward and to the CS and expanded representation of CS frequencies
      in the tonotopic map of A1. ARPs have the major characteristics of associative
      memory: They are highly specific, discriminative, rapidly acquired, exhibit
      consolidation over hours and days, and can be retained indefinitely. Evidence to
      date suggests that ARPs encode the level of acquired behavioral importance of
      stimuli. The nucleus basalis cholinergic system is sufficient both for the
      induction of ARPs and the induction of specific auditory memory. Investigation of
      ARPs has attracted workers with diverse backgrounds, often resulting in
      behavioral approaches that yield data that are difficult to interpret. The
      advantages of studying associative representational plasticity are emphasized, as
      is the need for greater behavioral sophistication.

PMID- 17202428
TI  - Aging affects motor learning but not savings at transfer of learning.
AB  - Two important components of skill learning are the learning process itself (motor
      acquisition) and the ability to transfer what has been learned to new task
      variants (motor transfer). Many studies have documented age-related declines in
      the ability to learn new manual motor skills. In this study, I tested whether the
      degree of savings at transfer of learning is similarly affected by advancing age.
      Young and older adults made aiming movements with a joystick to hit targets
      presented on a computer screen, with real-time feedback display of their
      movement. They adapted to three different rotations of the feedback display in a
      sequential fashion, with return to the normal feedback display between each.
      Adaptation performance was better when it was preceded by other adaptive
      experiences, regardless of age.

PMID- 17202429
TI  - Reconsolidation of episodic memories: a subtle reminder triggers integration of
      new information.
AB  - Recent demonstrations of "reconsolidation" suggest that memories can be modified
      when they are reactivated. Reconsolidation has been observed in human procedural
      memory and in implicit memory in infants. This study asks whether episodic memory
      undergoes reconsolidation. College students learned a list of objects on Day 1.
      On Day 2, they received a reminder or not, and then learned a second list. Memory
      for List 1 was tested immediately on Day 2 (Experiment 2) or on Day 3 (Experiment
      1). Although the reminder did not moderate the number of items recalled from List
      1 on either day, subjects who received a reminder incorrectly intermixed items
      from the second list when recalling List 1 on Day 3. Experiment 2 showed that
      this effect does not occur immediately and thus is time-dependent. The reminder
      did not affect memory for List 2 on Day 3 (Experiment 3), demonstrating that
      modification occurred only for the original memory (List 1). The study
      demonstrates the crucial role of reminders for the modification of episodic
      memory, that reconsolidation of episodic memory is time-dependent, and, in
      contrast to previous reconsolidation findings, that reconsolidation is also a
      constructive process, one that supports the incorporation of new information in
      memory.

PMID- 17202430
TI  - Enriching the environment of alphaCaMKIIT286A mutant mice reveals that LTD occurs
      in memory processing but must be subsequently reversed by LTP.
AB  - alphaCaMKII(T286A) mutant mice lack long-term potentiation (LTP) in the
      hippocampal CA1 region and are impaired in spatial learning. In situ
      hybridization confirms that the mutant mice show the same developmental
      expression of alphaCaMKII as their wild-type littermates. A simple hypothesis
      would suggest that if LTP is a substrate for learning, then enriching the
      environment should cause learning-dependent changes in wild-type mice that have
      LTP. Such changes would not be seen in LTP-deficient alphaCaMKII(T286A) mutants.
      Excitatory synaptic currents in CA1 neurons, recorded with patch clamp in brain
      slices, revealed that enrichment induces an increase in glutamate release
      probability and a decreased miniature current amplitude. Confocal microscopy also
      showed dendritic spine density to be reduced. However, contrary to the hypothesis
      above, these enrichment-induced changes occur only in the mutant mice and are not
      detectable in wild-type littermates. We suggest that enrichment induces
      alphaCaMKII-independent changes in both wild-type and mutant mice. Such changes
      may be subsequently reversed in wild-type animals via alphaCaMKII-dependent
      mechanisms, such as LTP. Reversal of plasticity has long been hypothesized to be
      essential for the hippocampus to maintain its role in memory processing. The
      inability to reverse plasticity in alphaCaMKII(T286A) mutant mice would then
      result in impairment of spatial learning.

PMID- 17202431
TI  - Clinicopathologic features of frontotemporal dementia with progranulin sequence
      variation.
AB  - BACKGROUND: Frontotemporal lobar degeneration with ubiquitin-immunoreactive (ub
      ir) inclusions (FTLD-U) has been associated with frontotemporal dementia (FTD)
      and ALS. Recently, mutations in Progranulin (PGRN), predicted to cause premature
      truncation of the PGRN coding sequence, were found in patients with inherited
      FTLD-U and ub-ir neuronal intranuclear inclusions (NII). OBJECTIVE: To describe
      clinical, pathologic, and genetic features of three FTD patients having either a
      family history of FTD (A.III.1 and B.II.1) or of ALS (C.III.1). METHODS: Patients
      underwent a single clinical assessment, MRI, and [(18)F]fluorodeoxyglucose PET
      brain scan. Neuropathologic examination and genetic analyses were carried out.
      RESULTS: Patients presented clinically with the behavioral variant of FTD.
      Language dysfunctions were marked with comprehension being particularly affected.
      Neuroimaging revealed frontotemporal atrophy and glucose hypometabolism, with
      predominant left-side involvement, in Patients A.III.1 and B.II.1. Subject
      C.III.1 displayed mild atrophy and symmetric anterior hypometabolism. All
      patients were neuropathologically diagnosed with FTLD-U. Ub-ir NII were noted in
      Patients A.III.1 and B.II.1 but were absent in Patient C.III.1. The following
      PGRN sequence variations were found: IVS6-2A-->G (A.III.1), R493X (B.II.1), and
      R433W (C.III.1). IVS6-2A-->G may lead to skipping of exon 7 with consequent
      frameshift of the coding sequence and premature termination of PGRN translation.
      CONCLUSIONS: We have found two PGRN mutations associated with FTD, in affected
      individuals who are members of families with possible autosomal dominant FTD. A
      third PGRN sequence variation (R433W) was found in an FTD patient with family
      history of ALS.

PMID- 17202432
TI  - Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson
      disease.
AB  - OBJECTIVE: This multicenter, randomized, double-blind study was performed to
      compare the safety and efficacy of the once-daily dopamine agonist rotigotine, in
      a continuous-dosing transdermal-patch formulation, vs placebo in patients with
      early-stage Parkinson disease (PD). METHODS: Patients were randomized to receive
      placebo (n = 96) or rotigotine (n = 181), starting at 2 mg/24 h (10-cm(2) patch
      size; 4.5-mg total drug content), titrated weekly up to 6 mg/24 h (30-cm(2) patch
      size; 13.5-mg total drug content), and then maintained for 6 months. The primary
      efficacy measures were 1) the change in the Unified Parkinson's Disease Rating
      Scale (UPDRS) scores (parts II and III) from baseline to end of treatment and 2)
      responder rates (patients with > or =20% improvement). RESULTS: Patients
      receiving rotigotine had a mean absolute difference of 5.28 (+/-1.18) points
      lower in UPDRS subtotal scores compared with those receiving placebo (p <
      0.0001). The mean change in part III motor scores was -3.50 (+/-7.26) (n = 177)
      and was the greatest contributor to UPDRS improvement. The rotigotine group had
      more responders (48 vs 19%; p < 0.0001). The most commonly reported adverse
      events were application site reactions (44% rotigotine vs 12% placebo), nausea
      (41 vs17%), somnolence (33 vs 20%), and dizziness (19 vs 13%), and most were mild
      or moderate in intensity. CONCLUSIONS: Transdermal rotigotine, when titrated to a
      dosage of 6 mg/24 h, was effective for the treatment of early-stage Parkinson
      disease in this trial. Adverse events were similar to those found with other
      transdermal systems and dopamine agonists.

PMID- 17202433
TI  - Are plasma citrulline and glutamine biomarkers of intestinal absorptive function
      in patients with short bowel syndrome?
AB  - Sensitive biomarkers for intestinal absorptive function would be clinically
      useful in short bowel syndrome (SBS). Citrulline (Cit) is a product of the
      metabolism of glutamine (Gln) and derived amino acids by enterocytes. Cit is
      produced almost exclusively by the gut, which is also a major site of Gln
      metabolism. The goals of this study were to examine whether plasma Cit and Gln
      concentrations are biomarkers of residual small intestinal length and nutrient
      absorptive functions in adult SBS patients followed prospectively. We studied 24
      stable adults with severe SBS receiving chronic parenteral nutrition (PN) in a
      double-blind, randomized trial of individualized dietary modification +/-
      recombinant human growth hormone (GH). During a baseline week, intestinal
      absorption studies (% absorption of fluid, kcal, nitrogen, fat, carbohydrate,
      sodium, phosphorus, and magnesium) were performed and concomitant plasma Cit and
      Gln concentrations determined. Individualized dietary modification and treatment
      with subcutaneous injection of placebo (n = 9) or GH (0.1 mg/kg daily x 21 days,
      then 3 times/week; n = 15) were then begun. PN weaning was initiated after week 4
      and continued as tolerated for 24 weeks. Repeat plasma amino acid determination
      and nutrient absorption studies were performed at weeks 4 and 12. Residual small
      bowel length at baseline was positively correlated with baseline plasma Cit (r =
      0.467; p = .028). However, no significant correlations between absolute Cit or
      Gln concentrations and the percent absorption of nutrient substrates at any time
      point were observed. Similarly, no correlation between the change in Cit or GLN
      concentration and the change in % nutrient absorption was observed (baseline vs
      weeks 4 and 12, respectively). By weeks 12 and 24, 7 and 13 subjects were weaned
      completely from PN, respectively. However, baseline plasma Cit or Gln did not
      predict PN weaning at these time points. We concluded that plasma Cit (but not
      Gln) concentrations appeared to be an indicator of small intestinal length in
      adult SBS. However, neither plasma Cit nor Gln was a biomarker for intestinal
      absorptive function in this cohort of patients with SBS.

PMID- 17202434
TI  - Use of parenteral nutrition in patients receiving isolated kidney or simultaneous
      pancreas/kidney transplantation.
AB  - BACKGROUND: There is little information available on the use of parenteral
      nutrition (PN) in patients after a kidney (KID) or simultaneous pancreas-kidney
      (SPK) transplantation. This study examined the indications and use of PN in these
      patients. METHODS: Retrospective study of 25 patients (12M/13F; mean age: 51 +/-
      11 years old) receiving PN after KID or SPK transplantation. Patients were
      divided in 2 groups according to the number of PN days (group A = <7 days and
      group B = >7 days). RESULTS: Overall mortality was 16% (group A: 0/7; group B:
      4/18). Postoperative ileus (n = 7), intestinal fistula (n = 5), and
      nausea/vomiting (n = 4) were the most common indications for PN. Functional
      disorders accounted for 56% (14/25) of the indications for PN. Factors
      differentiating group A (7/25; median = 5 [4-6] days) from group B (18/25; median
      =9 [7-31] days) included a significantly higher preoperative serum albumin, SPK
      transplantation for the first time, and diagnosis of ileus as the indication for
      PN initiation. CONCLUSIONS: Functional disorders of the digestive tract are the
      primary reason for initiation of PN in isolated KID and SPK transplantation
      patients. Well-nourished patients undergoing their first SPK transplantation who
      develop postoperative ileus usually do not need nutrition intervention.

PMID- 17202435
TI  - Supplementation of omega-3 fatty acids in parenteral nutrition beneficially
      alters phospholipid fatty acid pattern.
AB  - BACKGROUND: The clinical safety and the uptake of omega-3 polyunsaturated fatty
      acids (PUFA) into the serum phospholipids and erythrocyte membranes after
      administration of fish-oil-supplemented parenteral nutrition (PN) was
      investigated in colorectal surgical patients. METHODS: Forty patients undergoing
      colorectal surgery (n = 40) and with an indication for PN were enrolled in a
      prospective, double-blind, randomized study to receive an omega-3 PUFA
      supplemented 20% lipid emulsion (Lipoplus; B. Braun Melsungen, Melsungen,
      Germany; test group, n = 19) for 5 days postoperatively. The control group
      received a standard 20% fat emulsion (Lipofundin MCT/LCT, B. Braun Melsungen,
      Melsungen, Germany, control group, n = 21). Clinical outcome parameters and
      safety were assessed by means of adverse events recording clinical parameters and
      hematologic analyses. The contents of eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), as well as arachidonic acid (AA), in phospholipid
      fractions in plasma and in erythrocytes were analyzed preoperatively, on
      postoperative days 1, 6, and 10 using liquid gas chromatography. RESULTS: Both
      fat emulsions were well tolerated, and none of the adverse events was considered
      to be related to treatment. Postoperative infectious complications occurred in 4
      patients of the omega-3 PUFA group vs 7 patients in the control group. As
      compared with the control group, the omega-3 PUFA group had significantly
      increased levels of EPA in the membranes of the erythrocytes in postoperative day
      6 (2.0% +/- 0.9% vs 0.8% +/- 0.5% fatty acid methyl esters, [FAME]) and
      postoperative day 10 (2.1% +/- 0.8% vs 0.9% +/- 0.7% FAME, p < .05). Also, the
      EPA levels in the serum phospholipids were significantly higher than in the
      control group on the same postoperative days (7.0% +/- 2.6% vs 1.3% +/- 0.8% and
      3.6% +/- 1.0% vs 1.0% +/- 0.4% FAME, p < .05). The DHA levels in the serum
      phospholipids were significantly higher in the omega-3 PUFA group compared with
      the control on postoperative days 6 and 10 (11.8% +/- 1.9% vs 8.4% +/- 1.5% and
      11.2% +/- 1.6% vs 8.5% +/- 1.4% FAME, p < .05). AA levels were not significantly
      different in the both groups. CONCLUSIONS: Omega-3-fatty-acids-supplemented fat
      emulsions for parenteral administration are safe and very well tolerated. This
      study demonstrates that parenteral administration of omega-3-PUFA-enriched fat
      emulsions leads to increased incorporation of EPA and DHA into phospholipids in
      serum and erythrocytes, whereas AA levels remain unchanged. Thus, postoperative
      parenteral administration of omega-3-PUFA-enriched lipid emulsions could have an
      impact on the postoperative inflammatory response after abdominal surgery and
      could be used in standard postoperative care when PN is indicated.

PMID- 17202436
TI  - Prevention of cancer cachexia by pyrrolidine dithiocarbamate (PDTC) in colon 26
      tumor-bearing mice.
AB  - BACKGROUND: The precise mechanism of cancer cachexia is not fully elucidated.
      This study was aimed to assess the effect of pyrrolidine dithiocarbamate (PDTC,
      an inhibitor of NFkappaB) on interleukin (IL)-6 synthesis and cachexia in colon
      26 tumor-bearing mice. METHODS: Murine colon 26 adenocarcinoma cells were
      inoculated subcutaneously in male BALB/c mice to induce cachexia. Saline and
      various doses of PDTC (10, 50, or 100 mg/kg/d) were given intraperitoneally daily
      from 7 days after tumor inoculation to killing. Body weight, food intake, and
      tumor volume were monitored daily. Serum and tumor tissue levels of IL-6, serum
      biochemical indicator, and activity of NFkappaB in tumor tissue were investigated
      in all mice. RESULTS: Significant tissue wasting was observed in all tumor
      bearing mice. By day 16, carcass weights of untreated tumor-bearing mice were
      about 71.3% of healthy controls (p < .01), and the weights of gastrocnemius
      muscle and epididymal fat were lowered by 42.4% and 70.4% (p < .01),
      respectively. Furthermore, tumor-bearing caused a significant decrease of serum
      albumin, glucose, and triglyceride (p < .01) and increase of IL-6 (p < .01) in
      serum and tumor tissues. Administration of PDTC dose dependently inhibited the
      NFkappaB activation in tumor tissues, inhibited IL-6 synthesis of the tumor
      cells, and attenuated the wasting of carcass weight, gastrocnemius muscle, and
      epididymal fat. Tumor growth was inhibited by PDTC with 100 mg/kg (p < .05). No
      differences of food intake were found between groups (p > .05). CONCLUSIONS:
      These results suggest that PDTC, an inhibitor of NFkappaB, can attenuate the
      development of cachexia in colon 26 tumor-bearing mice through inhibition of IL-6
      synthesis regulated by NFkappaB.

PMID- 17202437
TI  - Does glutamine supplementation decrease the response of muscle glutamine
      synthesis to fasting in muscle in adult and very old rats?
AB  - BACKGROUND: Glutamine synthetase (GS), a key enzyme in the production of
      glutamine, is preserved in rat skeletal muscle during aging but is increased with
      advanced age in vivo. The aim of this study was to determine whether glutamine
      supplementation affects up-regulation of GS by fasting in vivo in adult and very
      old female rats. METHODS: Muscle GS activities were assessed in 5-day-fasted
      female Wistar adult (6 months) and very old (27 months) rats refed and
      supplemented with glutamine or other amino acids (alanine or glycine). Fed rats
      were used to investigate the possible effect of glutamine supplementation in the
      fed state. RESULTS: After 5 days' fasting, the up-regulated GS activity was
      decreased whatever the type of amino acid supplementation (glutamine, alanine,
      and glycine) in adults, whereas it was only decreased by glutamine
      supplementation in very old rats). In the fed state, no effect of glutamine
      supplementation was observed even if GS activity remained up-regulated whatever
      the age and the period of supplementation. CONCLUSIONS: These results confirm
      that glutamine has a specific role in very old rats. The up-regulated GS activity
      was decreased by an exogenous supply of glutamine only if intramuscular glutamine
      was depleted; this was confirmed by studies in the fed state. The up-regulated GS
      activity in both fed and fasted rats may be associated with increased glutamine
      requirements in the whole body.

PMID- 17202438
TI  - Alanine-glutamine dipeptide (AGD) inhibits expression of inflammation-related
      genes in hemorrhagic shock.
AB  - BACKGROUND: Inflammatory factors play an important role in the production of
      cellular damage after shock and reperfusion. Glutamine has been used to modulate
      the inflammatory response. Alanine-glutamine dipeptide (AGD) is a glutamine
      source. The hypothesis of the present study is that AGD given during
      resuscitation will suppress postshock expression of messenger ribonucleic acid
      (mRNA) for tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1beta) and
      inducible nitric oxide synthase (iNOS). METHODS: Male Sprague-Dawley rats (n =
      74, 350 g +/- 30 g) were randomly assigned to 5 groups. Under isoflurane
      anesthesia, the femoral artery and vein were cannulated. Hemorrhagic shock was
      induced by withdrawing blood through the arterial cannula until the mean arterial
      pressure (MAP) was 25-30 mm Hg and maintained at the level for 30 minutes with
      further withdrawals. Resuscitation was carried out by giving 21 mL/kg Ringer's
      lactate (LR) with or without the administration of AGD (936 mg/kg) and returning
      the shed blood. Controls were normal (anesthesia only), sham (surgical
      preparation), and shock (preparation and shock). Rats (n = 45, 9 per group) were
      killed 30 minutes after completion of resuscitation. Liver samples were
      collected, and total RNA was isolated for reverse transcription-polymerase chain
      reaction analysis of mRNA (TNF-alpha, IL-1beta, iNOS, and beta-actin). RESULTS:
      MAP recovered more quickly in the AGD group than in the LR group. Increased
      expression of liver mRNA for TNF-alpha, IL-1beta, and iNOS was seen after
      hemorrhagic shock and resuscitation. AGD treatment significantly reduced mRNA
      expression for all 3. CONCLUSIONS: AGD modified the expression of genes
      controlling cytokines and iNOS in the liver. This agent is a potential treatment
      for hemorrhagic shock.

PMID- 17202439
TI  - Effects of cysteine on the pharmacokinetic parameters of omeprazole in rats with
      protein-calorie malnutrition: partial restoration of some parameters to control
      levels by oral cysteine supplementation.
AB  - BACKGROUND: It has been reported that omeprazole is mainly metabolized via the
      hepatic cytochrome (CYP) 1A1/2, 3A1/2, and 2D1, and the expressions and mRNA
      levels of CYP1A2, 2C11, and 3A1/2 decreased in protein-calorie malnutrition (PCM)
      rats compared with controls. Interestingly, the decreased CYP1A2, 2C11, and 3A1/2
      in PCM rats returned fully or partially to control levels by oral cysteine
      supplementation (PCMC rats). Hence, it could be expected that some
      pharmacokinetic parameters of omeprazole might change in PCM rats and partially
      restore to control levels in PCMC rats. The purpose of this study is to
      investigate the pharmacokinetic changes of omeprazole in PCM rats and restoration
      of the parameters in PCMC rats to control levels. METHODS: Omeprazole was
      administered intravenously (20 mg/kg) and orally (40 mg/kg) to control, PCM, and
      PCMC rats. RESULTS: The following pharmacokinetic parameters were changed in PCM
      rats and partially returned to control levels in PCMC rats: the area under the
      plasma concentration-time curve (AUC; 387, 762, and 539 microg min/mL for
      control, PCM, and PCMC rats, respectively, after intravenous [IV] administration,
      and the corresponding values after oral administration: 115, 304, and 201 microg
      min/mL), total body clearance (51.7, 25.5, and 37.1 mL/min/kg, respectively),
      nonrenal clearance (51.5, 25.4, and 36.1 mL/min/kg, respectively), and in vitro
      intrinsic clearance (0.158, 0.118, and 0.138 mL/min/mg protein). CONCLUSIONS: PCM
      was associated with significant changes in some omeprazole pharmacokinetics and
      the pharmacokinetic parameters restored to control levels by oral cysteine.

PMID- 17202440
TI  - Parenteral nutrition and fasting reduces mucosal addressin cellular adhesion
      molecule-1 (MAdCAM-1) mRNA in Peyer's patches of mice.
AB  - BACKGROUND: Mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) in Peyer's
      patches (PP) is the gateway molecule for cellular migration into the mucosal
      immune system. Lack of enteral feeding during parenteral nutrition (PN) rapidly
      decreases PP MAdCAM-1, leading to drops in mucosal T and B cells and intestinal
      and respiratory IgA. We determined the molecular events associated with MAdCAM-1
      mRNA and protein during PN (short and long term) and fasting (1 and 2 days).
      METHODS: Experiment 1: Cannulated mice received PN for 8 hours (short-term PN, n
      = 6) or chow + saline (chow, n = 6). Experiment 2: Cannulated mice received PN
      (long-term PN, n = 4) or chow (n = 3) for 5 days. Experiment 3: Noncannulated
      chow mice were fasted for 1 and 2 days (n = 2/time). Total cellular RNA from the
      PP was quantified for MAdCAM-1 mRNA by real-time polymerase chain reaction (PCR).
      MAdCAM-1 protein was measured by Western blot. RESULTS: PN rapidly down-regulated
      MAdCAM-1 gene expression. After 8 hours of PN with lack of enteral feeding,
      MAdCAM-1 mRNA levels dropped 20% (0.8-fold vs chow, p > .05); 5 days of PN
      reduced MAd-CAM-1 levels 64% (0.34-fold vs chow, p < .05). PN reduced MAdCAM-1
      protein levels by 30% (chow: 329 +/- 14 vs PN: 230 +/- 35, p < .05) after 5 days.
      Fasting of uncannulated mice decreased MAdCAM-1 mRNA levels by 16% (0.84-fold, p
      < .05) at day 1 and 30% (0.7-fold, p < .05) by day 2 compared with chow.
      CONCLUSIONS: Both PN with lack of enteral feeding and fasting down-regulate
      MAdCAM-1 mRNA and protein levels in PP. The MAdCAM-1 changes are due to lack of
      enteral stimulation rather than toxic effects of PN.

PMID- 17202442
TI  - Resting energy expenditure during mechanical ventilation and its relationship
      with the type of lesion.
AB  - BACKGROUND: Resting energy expenditure (REE) of critically ill patients is
      usually calculated according to basal energy expenditure obtained from Harris
      Benedict equations traditionally corrected by different stress factors, resulting
      in a variable accuracy for the individual patient. The objective of this study
      was to investigate whether or not the type of lesion affects the metabolism level
      of critically ill patients treated with mechanical ventilation. We performed a
      retrospective study measuring the REE of critically ill patients with 3 different
      types of lesions (trauma, medical, surgical) who were treated with mechanical
      ventilation and sedation. Each lesion group of patients was matched with another
      group, differing in the type of lesion, according to gender, age, and weight.
      METHODS: Eighty-seven from a database of 175 critically ill patients undergoing
      indirect calorimetry were necessary for matching. Twenty matched pairs of
      patients for each of the following different type of lesion were obtained:
      medical vs surgical, medical vs trauma, and surgical vs trauma. RESULTS: The mean
      REE difference was 52 kcal/d (95% confidence interval [CI] of -136 -241 kcal/d)
      for the medical vs surgical group, 5 kcal/d (95% CI -236 -247 kcal/d) for the
      medical vs trauma group and 43 kcal/d (95% CI of -132-219 kcal/d) for the
      surgical vs trauma group. No statistically significant differences between groups
      were found in the measured REE. We did not find statistically significant
      differences in the measured REE of patients with and without infection.
      CONCLUSIONS: Critically ill patients with different types of lesion treated with
      mechanical ventilation have similar measured REE.

PMID- 17202441
TI  - Establishing the use of body mass index as an indicator of nutrition risk in
      children with cancer.
AB  - BACKGROUND: The negative health consequences of malnutrition in the pediatric
      oncology patient are well known. The purpose of this study was to determine the
      usefulness of body mass index (BMI) for age as a tool to prospectively identify
      pediatric cancer patients at risk for malnutrition and to determine the BMI
      percentile that would be required to identify at-risk patients. METHODS: This
      study was conducted by a retrospective chart review of 1839 newly diagnosed acute
      lymphoblastic leukemia patients at St. Jude Children's Research Hospital. Those
      falling below the 10(th) percentile on any one category of height for age (HFA),
      weight for age (WFA), or weight for height (WFH) were classified with regard to
      nutrition risk and compared with those identified as at risk by BMI for age
      (BFA). The BMI percentiles of the lower 9(th)-11(th) percentile patients on the
      HFA, WFA, and WFH growth charts were averaged in an attempt to determine a useful
      value to identify nutrition risk. RESULTS: Lack of agreement was found to exist
      between BFA and HFA in identifying patients at risk for malnutrition, and also
      between BFA and WFA. Significant agreement was found to exist between BFA and
      WFH. The BMI percentile required to identify those at risk for malnutrition by
      the other growth charts would classify too many patients as being at risk for
      malnutrition to be considered clinically useful. CONCLUSIONS: Although research
      has shown BMI is appropriate to use in the nutrition assessment of children, its
      usefulness has not been confirmed in the pediatric oncology patient; therefore,
      further study is warranted. BFA assessment should be included in the nutrition
      survey of new pediatric oncology patients, along with other parameters, but it
      cannot be recommended as the sole indicator of nutrition status at this time.

PMID- 17202444
TI  - Wernicke's encephalopathy during parenteral nutrition.
AB  - BACKGROUND: Thiamine deficiency in humans affects the cardiovascular, muscular,
      nervous, and gastrointestinal systems. Wernicke's encephalopathy is described in
      alcoholism, in hyperemesis gravidarum, and in prolonged IV feeding without
      vitamin supplementation. METHODS: We report a case of a 66-year-old man
      undergoing surgery for acute necrotic-hemorrhagic pancreatitis, who presented a
      Wernicke's syndrome during parenteral nutrition (PN). After surgery, he was
      treated with infusion of industrial 3-compartment bags, without vitamin
      supplementation. On the seventh postoperative day, nausea and vomiting began, and
      5 days later the patient showed diplopia, ataxia, general muscular stiffness,
      reduction of osteotendinous reflexes, confusional state, and thrombocytopenia.
      The magnetic resonance scan evidenced pathologic changes in the medial thalamus,
      in the third and fourth ventricular floor, in the cerebellar vermis, and in the
      periaqueductal gray substance. RESULTS: All neurologic signs and platelet blood
      count gradually normalized after IV supplementation of thiamine, 100 mg daily.
      The magnetic resonance scan repeated 40 days after the first one was normal.
      CONCLUSIONS: Our report points out the risk of incorrect procedures in management
      of industrial 3-compartment bags. Moreover, we suggest that thrombocytopenia may
      be related to thiamine deficiency.

PMID- 17202443
TI  - Gastric residual volume (GRV) and gastric contents measurement by refractometry.
AB  - BACKGROUND: Traditional use of gastric residual volumes (GRVs), obtained by
      aspiration from a nasogastric tube, is inaccurate and cannot differentiate
      components of the gastric contents (gastric secretion vs delivered formula). The
      use of refractometry and 3 mathematical equations has been proposed as a method
      to calculate the formula concentration, GRV, and formula volume. In this paper,
      we have validated these mathematical equations so that they can be implemented in
      clinical practice. METHODS: Each of 16 patients receiving a nasogastric tube had
      50 mL of water followed by 100 mL of dietary formula (Osmolite HN, Abbott
      Laboratories, Columbus, OH) infused into the stomach. After mixing, gastric
      content was aspirated for the first Brix value (BV) measurement by refractometry.
      Then, 50 mL of water was infused into the stomach and a second BV was measured.
      The procedure of infusion of dietary formula (100 mL) and then water (50 mL) was
      repeated and followed by subsequent BV measurement. The same procedure was
      performed in an in vitro experiment. Formula concentration, GRV, and formula
      volume were calculated from the derived mathematical equations. RESULTS: The
      formula concentrations, GRVs, and formula volumes calculated by using
      refractometry and the mathematical equations were close to the true values
      obtained from both in vivo and in vitro validation experiments. CONCLUSIONS:
      Using this method, measurement of the BV of gastric contents is simple,
      reproducible, and inexpensive. Refractometry and the derived mathematical
      equations may be used to measure formula concentration, GRV, and formula volume,
      and also to serve as a tool for monitoring the gastric contents of patients
      receiving nasogastric feeding.

PMID- 17202445
TI  - The 70:30 health care system.

PMID- 17202447
TI  - Images in clinical medicine. Papillary fibroelastoma of the pulmonary artery.

PMID- 17202448
TI  - Health care on the hill--Democrats set the agenda.

PMID- 17202446
TI  - Pandemic flu: clinical management of patients with an influenza-like illness
      during an influenza pandemic. Provisional guidelines from the British Infection
      Society, British Thoracic Society, and Health Protection Agency in collaboration
      with the Department of Health.

PMID- 17202449
TI  - Medicare and erythropoietin.

PMID- 17202450
TI  - Drugs and valvular heart disease.

PMID- 17202451
TI  - A five-gene signature and clinical outcome in non-small-cell lung cancer.
AB  - BACKGROUND: Current staging methods are inadequate for predicting the outcome of
      treatment of non-small-cell lung cancer (NSCLC). We developed a five-gene
      signature that is closely associated with survival of patients with NSCLC.
      METHODS: We used computer-generated random numbers to assign 185 frozen specimens
      for microarray analysis, real-time reverse-transcriptase polymerase chain
      reaction (RT-PCR) analysis, or both. We studied gene expression in frozen
      specimens of lung-cancer tissue from 125 randomly selected patients who had
      undergone surgical resection of NSCLC and evaluated the association between the
      level of expression and survival. We used risk scores and decision-tree analysis
      to develop a gene-expression model for the prediction of the outcome of treatment
      of NSCLC. For validation, we used randomly assigned specimens from 60 other
      patients. RESULTS: Sixteen genes that correlated with survival among patients
      with NSCLC were identified by analyzing microarray data and risk scores. We
      selected five genes (DUSP6, MMD, STAT1, ERBB3, and LCK) for RT-PCR and decision
      tree analysis. The five-gene signature was an independent predictor of relapse
      free and overall survival. We validated the model with data from an independent
      cohort of 60 patients with NSCLC and with a set of published microarray data from
      86 patients with NSCLC. CONCLUSIONS: Our five-gene signature is closely
      associated with relapse-free and overall survival among patients with NSCLC.

PMID- 17202452
TI  - Multidrug-resistant Salmonella enterica serotype Typhimurium associated with pet
      rodents.
AB  - BACKGROUND: An estimated 1.4 million salmonella infections occur annually in the
      United States. The majority of these infections are foodborne, but many are
      acquired by contact with animals. In August 2004, isolates of Salmonella enterica
      serotype Typhimurium, which were indistinguishable from one another by pulsed
      field gel electrophoresis (PFGE), were obtained from eight hamsters from a
      Minnesota pet distributor. We conducted an investigation to determine whether
      human cases of salmonella could be linked to this rodent-borne strain. METHODS:
      To identify cases of human infection with S. enterica serotype Typhimurium
      potentially related to pet rodents, we reviewed salmonella PFGE patterns
      submitted to the National Molecular Subtyping Network for Foodborne Disease
      Surveillance. Patients with isolates matching the hamster strain were interviewed
      about exposure to pet rodents. Implicated rodents were traced to pet stores,
      distributors, and breeders. RESULTS: We identified matching S. enterica serotype
      Typhimurium isolates from 28 patients in whom the onset of illness occurred
      between December 2003 and September 2004. Of 22 patients (or in the case of
      children, their parents) interviewed, 13 patients (59%) in 10 states reported
      exposure to pet hamsters, mice, or rats, and 2 (9%) had secondary infections. The
      median age of the 15 patients with primary or secondary rodent exposure was 16
      years, and 6 patients (40%) were hospitalized. Thirteen associated pet stores
      supplied by seven distributors were identified in 10 states. No single source of
      the rodents was identified. The outbreak strain of S. enterica serotype
      Typhimurium was cultured from a patient's pet mouse and from seven hamsters from
      pet stores. Closely related S. enterica serotype Typhimurium isolates were
      cultured from rodent cages and reusable transport containers at a pet
      distributor. Human, rodent, and environmental isolates were resistant to
      ampicillin, chloramphenicol, streptomycin, sulfisoxazole, and tetracycline.
      CONCLUSIONS: Pet rodents probably are an underrecognized source of human
      salmonella infection.

PMID- 17202453
TI  - Dopamine agonists and the risk of cardiac-valve regurgitation.
AB  - BACKGROUND: Case reports and echocardiographic studies suggest that the ergot
      derived dopamine agonists pergolide and cabergoline, used in the treatment of
      Parkinson's disease and the restless legs syndrome, may increase the risk of
      cardiac-valve regurgitation. METHODS: We used data from the United Kingdom
      General Practice Research Database to identify a population-based cohort
      comprising 11,417 subjects 40 to 80 years of age who were prescribed
      antiparkinsonian drugs between 1988 and 2005. We conducted a nested case-control
      analysis within this cohort in which each patient with newly diagnosed cardiac
      valve regurgitation was matched with up to 25 control subjects from the cohort,
      according to age, sex, and year of entry into the cohort. Incidence-rate ratios
      for cardiac-valve regurgitation with the use of different dopamine agonists were
      estimated by conditional logistic-regression analysis. RESULTS: Of 31 case
      patients with newly diagnosed cardiac-valve regurgitation, 6 were currently
      exposed to pergolide, 6 were currently exposed to cabergoline, and 19 had not
      been exposed to any dopamine agonist within the previous year. The rate of
      cardiac-valve regurgitation was increased with current use of pergolide
      (incidence-rate ratio, 7.1; 95% confidence interval [CI], 2.3 to 22.3) and
      cabergoline (incidence-rate ratio, 4.9; 95% CI, 1.5 to 15.6), but not with
      current use of other dopamine agonists. CONCLUSIONS: In this study, use of the
      dopamine agonists pergolide and cabergoline was associated with an increased risk
      of newly diagnosed cardiac-valve regurgitation.

PMID- 17202454
TI  - Valvular heart disease and the use of dopamine agonists for Parkinson's disease.
AB  - BACKGROUND: Ergot-derived dopamine receptor agonists, often used in the treatment
      of Parkinson's disease, have been associated with an increased risk of valvular
      heart disease. METHODS: We performed an echocardiographic prevalence study in 155
      patients taking dopamine agonists for Parkinson's disease (pergolide, 64
      patients; cabergoline, 49; and non-ergot-derived dopamine agonists, 42) and 90
      control subjects. Valve regurgitation was assessed according to American Society
      of Echocardiography recommendations. The mitral-valve tenting area was also
      measured and used as a quantitative index for leaflet stiffening and apical
      displacement of leaflet coaptation. RESULTS: Clinically important regurgitation
      (moderate to severe, grade 3 to 4) in any valve was found with significantly
      greater frequency in patients taking pergolide (23.4%) or cabergoline (28.6%) but
      not in patients taking non-ergot-derived dopamine agonists (0%), as compared with
      control subjects (5.6%). The relative risk for moderate or severe valve
      regurgitation in the pergolide group was 6.3 for mitral regurgitation (P=0.008),
      4.2 for aortic regurgitation (P=0.01), and 5.6 for tricuspid regurgitation
      (P=0.16); corresponding relative risks in the cabergoline group were 4.6
      (P=0.09), 7.3 (P<0.001), and 5.5 (P=0.12). The mean mitral tenting area was
      significantly greater in ergot-treated patients and showed a linear relationship
      with the severity of mitral regurgitation. Patients treated with ergot
      derivatives who had grade 3 to 4 regurgitation of any valve had received a
      significantly higher mean cumulative dose of pergolide or cabergoline than had
      patients with lower grades. CONCLUSIONS: The frequency of clinically important
      valve regurgitation was significantly increased in patients taking pergolide or
      cabergoline, but not in patients taking non-ergot-derived dopamine agonists, as
      compared with control subjects. These findings should be considered in evaluating
      the risk-benefit ratio of treatment with ergot derivatives.

PMID- 17202455
TI  - Primary PCI for myocardial infarction with ST-segment elevation.

PMID- 17202456
TI  - Whipple's disease.

PMID- 17202457
TI  - Images in clinical medicine. Subconjunctival swelling--prolapse of orbital fat.

PMID- 17202458
TI  - Clinical problem-solving. A stain in time.

PMID- 17202459
TI  - Molecular signatures of lung cancer--toward personalized therapy.

PMID- 17202460
TI  - p53 and tumor suppression.

PMID- 17202461
TI  - Immunotherapy with a ragweed vaccine.

PMID- 17202462
TI  - Transmission of human herpesvirus 8 by blood transfusion.

PMID- 17202463
TI  - Medical education after the Flexner report.

PMID- 17202464
TI  - The tuberous sclerosis complex.

PMID- 17202465
TI  - Hyponatremia associated with escitalopram.

PMID- 17202467
TI  - DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2.
AB  - Disrupted-in-Schizophrenia-1 (DISC1) is a candidate gene for susceptibility of
      schizophrenia. In the accompanying paper (Taya et al., 2006), we report that
      DISC1 acts as a linker between Kinesin-1 and DISC1-interacting molecules, such as
      NudE-like, lissencephaly-1, and 14-3-3epsilon. Here we identified growth factor
      receptor bound protein 2 (Grb2) as a novel DISC1-interacting molecule. Grb2 acts
      as an adaptor molecule that links receptor tyrosine kinases and the Ras
      extracellular signal-regulated kinase (ERK) pathway. DISC1 formed a ternary
      complex with Grb2 and kinesin heavy chain KIF5A of Kinesin-1. In cultured rat
      hippocampal neurons, both DISC1 and Grb2 partially colocalized at the distal part
      of axons. Knockdown of DISC1 or kinesin light chains of Kinesin-1 by RNA
      interference inhibited the accumulation of Grb2 from the distal part of axons.
      Knockdown of DISC1 also inhibited the neurotrophin-3 (NT-3)-induced
      phosphorylation of ERK-1/2 at the distal part of axons and inhibited NT-3-induced
      axon elongation. These results suggest that DISC1 is required for NT-3-induced
      axon elongation and ERK activation at the distal part of axons by recruiting Grb2
      to axonal tips.

PMID- 17202468
TI  - DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through
      kinesin-1.
AB  - Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to
      schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms
      a complex with lissencephaly-1 (LIS1) and 14-3-3epsilon. 14-3-3epsilon is
      involved in the proper localization of NUDEL and LIS1 in axons. Although the
      functional significance of this complex in neuronal development has been
      reported, the transport mechanism of the complex into axons and their functions
      in axon formation remain essentially unknown. Here we report that Kinesin-1, a
      motor protein of anterograde axonal transport, was identified as a novel DISC1
      interacting molecule. DISC1 directly interacted with kinesin heavy chain of
      Kinesin-1. Kinesin-1 interacted with the NUDEL/LIS1/14-3-3epsilon complex through
      DISC1, and these molecules localized mainly at cell bodies and partially in the
      distal part of the axons. DISC1 partially colocalized with Kinesin family member
      5A, NUDEL, LIS1, and 14-3-3epsilon in the growth cones. The knockdown of DISC1 by
      RNA interference or the dominant-negative form of DISC1 inhibited the
      accumulation of NUDEL, LIS1, and 14-3-3epsilon at the axons and axon elongation.
      The knockdown or the dominant-negative form of Kinesin-1 inhibited the
      accumulation of DISC1 at the axons and axon elongation. Furthermore, the
      knockdown of NUDEL or LIS1 inhibited axon elongation. Together, these results
      indicate that DISC1 regulates the localization of NUDEL/LIS1/14-3-3epsilon
      complex into the axons as a cargo receptor for axon elongation.

PMID- 17202469
TI  - Passive immunization with anti-ganglioside antibodies directly inhibits axon
      regeneration in an animal model.
AB  - Recent studies have proposed that neurite outgrowth is influenced by specific
      nerve cell surface gangliosides, which are sialic acid-containing
      glycosphingolipids highly enriched in the mammalian nervous system. For example,
      the endogenous lectin, myelin-associated glycoprotein (MAG), is reported to bind
      to axonal gangliosides (GD1a and GT1b) to inhibit neurite outgrowth. Clustering
      of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit
      neurite outgrowth in culture. In some human autoimmune PNS and CNS disorders,
      autoantibodies against GD1a or other gangliosides are implicated in
      pathophysiology. Because of neurobiological and clinical relevance, we asked
      whether anti-GD1a antibodies inhibit regeneration of injured axons in vivo.
      Passive transfer of anti-GD1a antibody severely inhibited axon regeneration after
      PNS injury in mice. In mutant mice with altered ganglioside or complement
      expression, inhibition by antibodies was mediated directly through GD1a and was
      independent of complement-induced cytolytic injury. The impaired regenerative
      responses and ultrastructure of injured peripheral axons mimicked the abortive
      regeneration typically seen after CNS injury. These data demonstrate that
      inhibition of axon regeneration is induced directly by engaging cell surface
      gangliosides in vivo and imply that circulating autoimmune antibodies can inhibit
      axon regeneration through neuronal gangliosides independent of endogenous
      regeneration inhibitors such as MAG.

PMID- 17202470
TI  - Taste-evoked responses to sweeteners in the nucleus of the solitary tract differ
      between C57BL/6ByJ and 129P3/J mice.
AB  - C57BL/6ByJ (B6) and 129P3/J (129) mice have different alleles of Tas1r3, which is
      thought to influence gustatory transduction of sweeteners, but studies have
      provided conflicting results regarding differences in sweetness perception
      between these strains. Single-unit taste-evoked activity was measured in the
      nucleus of the solitary tract (NST) in anesthetized B6 and 129 mice to address
      this controversy and to provide the first electrophysiological characterization
      of this nucleus in mice. Neurons had properties similar to those of NST cells in
      other species, including mean breadth-of-tuning of 0.8 +/- 0.0. There were no
      strain differences in neural responses at 600 or 900 ms after onset, but, with a
      5 s evoked period, responses to the sweeteners sucrose, maltose, acesulfame-K, SC
      45647, and D-phenylalanine were significantly larger in B6 relative to 129 mice.
      The strains did not differ in their mean response to NaSaccharin, but it evoked
      an across-neuron pattern of activity that was more similar to that of sucrose and
      less similar to that of NaCl in B6 mice compared with 129 mice. Neurons were
      classified as sucrose, NaCl, or HCl responsive, with the former more common in B6
      than 129 mice. Relative to other neurons, sucrose-responsive cells had delayed
      but more sustained sweetener responses in both strains. The results suggest that
      B6 mice perceive some sweeteners as more intense, but NaSaccharin as sweeter and
      less salty, relative to 129 mice. Furthermore, activity evoked by sweeteners
      includes a phasic response sent to different NST cells than a later tonic
      response, and only the latter differs between B6 and 129 mice.

PMID- 17202471
TI  - Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic
      hyperexcitability caused by developmental seizures.
AB  - Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid
      mediated short-term plasticity mechanism that couples postsynaptic Ca2+ rises to
      decreased presynaptic GABA release. Whether the gain of this retrograde synaptic
      mechanism is subject to long-term modulation by glutamatergic excitatory inputs
      is not known. Here, we demonstrate that activity-dependent long-term DSI
      potentiation takes place in hippocampal slices after tetanic stimulation of
      Schaffer collateral synapses. This activity-dependent, long-term plasticity of
      endocannabinoid signaling was specific to GABAergic synapses, as it occurred
      without increases in the depolarization-induced suppression of excitation.
      Induction of tetanus-induced DSI potentiation in vitro required a complex pathway
      involving AMPA/kainate and metabotropic glutamate receptor as well as CB1
      receptor activation. Because DSI potentiation has been suggested to play a role
      in persistent limbic hyperexcitability after prolonged seizures in the developing
      brain, we used these mechanistic insights into activity-dependent DSI
      potentiation to test whether interference with the induction of DSI potentiation
      prevents seizure-induced long-term hyperexcitability. The results showed that the
      in vitro, tetanus-induced DSI potentiation was occluded by previous in vivo fever
      induced (febrile) seizures, indicating a common pathway. Accordingly, application
      of CB1 receptor antagonists during febrile seizures in vivo blocked the seizure
      induced persistent DSI potentiation, abolished the seizure-induced upregulation
      of CB1 receptors, and prevented the emergence of long-term limbic
      hyperexcitability. These results reveal a new form of activity-dependent, long
      term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses,
      and demonstrate that blocking the induction of this plasticity abolishes the long
      term effects of prolonged febrile seizures in the developing brain.

PMID- 17202472
TI  - Hyperexcitability of distal dendrites in hippocampal pyramidal cells after
      chronic partial deafferentation.
AB  - Traumatic injury to the CNS results in chronic partial deafferentation of subsets
      of surviving neurons. Such injuries are often followed by a delayed but long
      lasting period of aberrant hyperexcitability. The cellular mechanisms underlying
      this delayed hyperexcitability are poorly understood. We developed an in vitro
      model of deafferentation and reactive hyperexcitability using organotypic
      hippocampal slice cultures to study the underlying cellular mechanisms. One week
      after transection of the Schaffer collateral and temporoammonic afferents to CA1
      neurons, brief tetanic stimulation of the residual excitatory synapses produced
      abnormally prolonged depolarizations, compared with responses in normally
      innervated neurons. Responses to weak stimulation, in contrast, were unaffected
      after deafferentation. Direct stimulation of distal apical dendrites using focal
      photolysis of caged glutamate triggered abnormally prolonged plateau potentials
      in the deafferented neurons when strong stimulation was given, but responses to
      weak stimulation were not different from controls. An identical phenotype was
      produced by chronic "chemical deafferentation" with glutamate receptor
      antagonists. Responses to strong synaptic and photolytic stimulation were
      selectively prolonged by small-conductance (SK-type) calcium-activated potassium
      channel blockers in normally innervated cells but not after deafferentation. No
      significant changes in SK2 mRNA or protein levels, GABAergic inhibition,
      glutamate receptor function, input resistance, or action potential parameters
      were observed after chronic deafferentation. We suggest that a posttranslational
      downregulation of SK channel function in thin distal dendrites is a significant
      contributor to deafferentation-induced reactive hyperexcitability.

PMID- 17202474
TI  - Serotonin modulates pallidal neuronal activity in the awake monkey.
AB  - Serotonin (5-HT)-containing neurons in the dorsal raphe project to the external
      and internal segments of the pallidum, which express several 5-HT receptors.
      Although the involvement of 5-HT in basal ganglia movement control has been
      suggested, little is known about the physiological action of 5-HT in the
      pallidum. Previous anatomical studies and in vitro physiological studies in other
      brain areas have suggested the following possibilities: (1) 5-HT suppresses
      GABAergic inhibition through presynaptic 5-HT1B receptors; (2) 5-HT decreases the
      firing of pallidal neurons through postsynaptic 5-HT1A receptors; and (3) 5-HT
      postsynaptically excites pallidal neurons through activation of 5-HT2C, 5-HT4, or
      5-HT7 receptors. To test these possibilities, we examined the effects of locally
      applied agonists and antagonists of 5-HT on spontaneous neuronal firing and on
      excitatory and inhibitory responses of pallidal neurons to electrical stimulation
      of the motor cortex in awake monkeys. Although in vivo experiments could not
      conclusively determine the receptor types or the active sites involved in the
      observed effects, the results suggested the following possibilities: (1) 5-HT
      strongly suppresses GABAergic inhibition probably through 5-HT1B receptors; (2)
      in the external pallidal segment, the suppression may involve additional
      receptors or mechanisms; and (3) 5-HT suppresses glutamatergic excitation
      probably through 5-HT1A (and not 5-HT1B) receptors. The present study did not
      isolate or identify the existence of strong, direct postsynaptic inhibitory or
      excitatory effects of 5-HT. Thus, present results imply that 5-HT modulates
      synaptic inputs of both pallidal segments and exerts a significant role in
      movement control.

PMID- 17202473
TI  - Appropriate inhibition of orexigenic hypothalamic arcuate nucleus neurons
      independently of leptin receptor/STAT3 signaling.
AB  - Leptin directly suppresses the activity of orexigenic neurons in the hypothalamic
      arcuate nucleus (ARC). We examined c-Fos-like immunoreactivity (CFLIR) as a
      marker of ARC neuronal activity in db/db mice devoid of the signaling form of the
      leptin receptor (LRb) and s/s mice that express LRb(S1138) [which is defective
      for STAT3 (signal transducer and activator of transcription) signaling]. Both
      db/db and s/s animals are hyperphagic and obese. This analysis revealed that
      CFLIR in agouti related peptide-expressing orexigenic ARC neurons is basally
      elevated in db/db but not s/s mice. Consistent with these observations,
      electrophysiologic evaluation of a small number of neurons in s/s animals
      suggested that leptin appropriately suppresses the frequency of IPSCs on ARC
      proopiomelanocortin (POMC) neurons that are mediated by the release of GABA from
      orexigenic ARC neurons. CFLIR in POMC neurons of s/s mice was also increased
      compared with db/db animals. Thus, these data suggest that, although LRb-->STAT3
      signaling is crucial for the regulation of feeding, it is not required for the
      acute or chronic regulation of orexigenic ARC neurons, and the activation of
      STAT3-mediated transcription by leptin is not required for the appropriate
      development of leptin responsiveness in these neurons.

PMID- 17202475
TI  - Synaptic protein dynamics in hibernation.
AB  - Neurons in hibernating mammals exhibit a dramatic form of plasticity during
      torpor, with dendritic arbors retracting as body temperature cools and then
      regrowing rapidly as body temperature rises. In this study, we used
      immunohistochemical imaging and Western blotting of several presynaptic and
      postsynaptic proteins to determine the synaptic changes that accompany torpor and
      to investigate the mechanisms behind these changes. We show torpor-related
      alterations in synaptic protein localization that occur rapidly and uniformly
      across several brain regions in a temperature-dependent manner. Entry into torpor
      is associated with a 50-65% loss of synapses, as indicated by changes in the
      extent of colocalization of presynaptic and postsynaptic markers. We also show
      that the loss of synaptic protein clustering occurring during entry into torpor
      is not attributable to protein loss. These findings suggest that torpor-related
      changes in synapses stem from dissociation of proteins from the cytoskeletal
      active zone and postsynaptic density, creating a reservoir of proteins that can
      be quickly mobilized for rapid rebuilding of dendritic spines and synapses during
      the return to euthermia. A mechanism of neural plasticity based on protein
      dissociation rather than protein breakdown could explain the hibernator's
      capacity for large, rapid, and repeated microstructural changes, providing a
      fascinating contrast to neuropathologies that are dominated by protein breakdown
      and cell death.

PMID- 17202476
TI  - The effect of spatial attention on contrast response functions in human visual
      cortex.
AB  - Previous electrophysiology data suggests that the modulation of neuronal firing
      by spatial attention depends on stimulus contrast, which has been described using
      either a multiplicative gain or a contrast-gain model. Here we measured the
      effect of spatial attention on contrast responses in humans using functional MRI.
      To our surprise, we found that the modulation of blood oxygenation level
      dependent (BOLD) responses by spatial attention does not greatly depend on
      stimulus contrast in visual cortical areas tested [V1, V2, V3, and MT+ (middle
      temporal area)]. An additive model, rather than a multiplicative or contrast-gain
      model best describes the attentional modulations in V1. This inconsistency with
      previous single-unit electrophysiological data has implications for the
      population-based neuronal source of the BOLD signal.

PMID- 17202477
TI  - Vocal premotor activity in the superior colliculus.
AB  - Chronic neural recordings were taken from the midbrain superior colliculus (SC)
      of echolocating bats while they were engaged in one of two distinct behavioral
      tasks: virtual target amplitude discrimination (VTAD) and real oscillating target
      tracking (ROTT). In the VTAD task, bats used a limited range of sonar call
      features to discriminate the amplitude category of echoes, whereas in the ROTT
      task, the bat produced dynamically modulated sonar calls to track a moving
      target. Newly developed methods for chronic recordings in unrestrained, behaving
      bats reveal two consistent bouts of SC neural activity preceding the onset of
      sonar vocalizations in both tasks. A short lead bout occurs tightly coupled to
      vocal onset (VTAD, -5.1 to -2.2 ms range, -3.6 +/- 0.7 ms mean lead time; ROTT, 
      3.0 to + 0.4 ms range, -1.2 +/- 1.3 ms mean lead time), and this activity may
      play a role in marking the time of each sonar emission. A long lead bout in SC
      activity occurs earlier and spreads over a longer interval (VTAD, -40.6 to -8.4
      ms range, -22.2 +/- 3.9 ms mean lead time; ROTT, -29.8 to -7.1 ms range, -17.5 +/
      9.1 ms mean lead time) when compared with short lead events. In the goal
      directed ROTT task, the timing of long lead event times vary with the bat's sonar
      call duration. This finding, along with behavioral studies demonstrating that
      bats adjust sonar call duration as they track targets at changing distance,
      suggests the bat SC contributes to range-dependent adjustments of sonar call
      duration.

PMID- 17202479
TI  - High thalamocortical theta coherence in patients with Parkinson's disease.
AB  - Research investigating the pathophysiology of Parkinson's disease (PD) mostly
      focuses on basal ganglia dysfunction. However, the main output from the basal
      ganglia is via the thalamus, and corticothalamic feedback constitutes the primary
      source of synapses in the thalamus. We therefore focus on the thalamocortical
      interplay. During the surgical intervention in six patients, local field
      potentials (LFPs) were recorded from pallidal-recipient thalamic nuclei VA and
      VLa. Simultaneously, EEG was recorded from several sites on the scalp. The
      highest thalamocortical coherence was found in the theta frequency band (4-9 Hz)
      with a mean peak frequency of 7.5 Hz. The magnitude of thalamocortical theta
      coherence was comparable to the magnitude of EEG coherence between scalp
      electrode pairs. Thalamocortical theta coherence reached 70% and was maximal with
      frontal scalp sites on both hemispheres. In the 13-20 Hz beta frequency band,
      maximal coherence was comparatively low but localized on the scalp ipsilateral to
      the site of thalamic LFP recording. The high thalamocortical coherence underlines
      the importance of thalamic function for the genesis of scalp EEG. We discuss the
      PD pathophysiology within the framework of dysrhythmic thalamocortical interplay,
      which has important consequences for the choice of therapeutic strategy in
      patients with severe forms of PD.

PMID- 17202480
TI  - Disynaptic amplification of metabotropic glutamate receptor 1 responses in the
      olfactory bulb.
AB  - Sensory systems often respond to rapid stimuli with high frequency and fidelity,
      as perhaps best exemplified in the auditory system. Fast synaptic responses are
      fundamental requirements to achieve this task. The importance of speed is less
      clear in the olfactory system. Moreover, olfactory bulb output mitral cells
      respond to a single stimulation of the sensory afferents with unusually long
      EPSPs, lasting several seconds. We examined the temporal characteristics,
      developmental regulation, and the mechanism generating these responses in mouse
      olfactory bulb slices. The slow EPSP appeared at postnatal days 10-11 and was
      mediated by metabotropic glutamate receptor 1 (mGluR1) and NMDA receptors. mGluR1
      contribution was unexpected because its activation usually requires strong, high
      frequency stimulation of inputs. However, dendritic release of glutamate from the
      intraglomerular network caused spillover-mediated recurrent activation of
      metabotropic glutamate receptors. We suggest that persistent responses in mitral
      cells amplify the incoming sensory information and, along with asynchronous
      inputs, drive odor-evoked slow temporal activity in the bulb.

PMID- 17202478
TI  - Nonvesicular release of glutamate by glial xCT transporters suppresses glutamate
      receptor clustering in vivo.
AB  - We hypothesized that cystine/glutamate transporters (xCTs) might be critical
      regulators of ambient extracellular glutamate levels in the nervous system and
      that misregulation of this glutamate pool might have important neurophysiological
      and/or behavioral consequences. To test this idea, we identified and functionally
      characterized a novel Drosophila xCT gene, which we subsequently named
      "genderblind" (gb). Genderblind is expressed in a previously overlooked subset of
      peripheral and central glia. Genetic elimination of gb causes a 50% reduction in
      extracellular glutamate concentration, demonstrating that xCT transporters are
      important regulators of extracellular glutamate. Consistent with previous studies
      showing that extracellular glutamate regulates postsynaptic glutamate receptor
      clustering, gb mutants show a large (200-300%) increase in the number of
      postsynaptic glutamate receptors. This increase in postsynaptic receptor
      abundance is not accompanied by other obvious synaptic changes and is completely
      rescued when synapses are cultured in wild-type levels of glutamate. Additional
      in situ pharmacology suggests that glutamate-mediated suppression of glutamate
      receptor clustering depends on receptor desensitization. Together, our results
      suggest that (1) xCT transporters are critical for regulation of ambient
      extracellular glutamate in vivo; (2) ambient extracellular glutamate maintains
      some receptors constitutively desensitized in vivo; and (3) constitutive
      desensitization of ionotropic glutamate receptors suppresses their ability to
      cluster at synapses.

PMID- 17202481
TI  - Depolarization and neurotransmitter regulation of vasopressin gene expression in
      the rat suprachiasmatic nucleus in vitro.
AB  - Vasopressin (VP) transcription in the rat suprachiasmatic nucleus (SCN) in
      organotypic culture was studied by in situ hybridization histochemistry using an
      intron-specific VP heteronuclear RNA probe. The circadian peak of VP gene
      transcription in the SCN in vitro is completely blocked by a 2 h exposure to
      tetrodotoxin (TTX) in the culture medium, and this TTX inhibition of VP gene
      transcription is reversed by exposure of the SCN to either forskolin or potassium
      depolarization. This suggests that an intrinsic, spontaneously active neuronal
      mechanism in the SCN is responsible for the cAMP- and depolarization-dependent
      pathways involved in maintaining peak VP gene transcription. In this paper, we
      evaluate a variety of neurotransmitter candidates, membrane receptors, and signal
      transduction cascades that might constitute the mechanisms responsible for the
      peak of VP gene transcription. We find that vasoactive intestinal peptide (VIP)
      and a VPAC2 (VIP receptor subtype 2) receptor-specific agonist, Ro-25-1553, are
      the most effective ligands tested in evoking a cAMP-mitogen-activated protein
      kinase signal transduction cascade leading to an increase in VP gene
      transcription in the SCN. In addition, a second independent pathway involving
      depolarization activating L-type voltage-gated calcium channels and a Ca
      dependent kinase pathway [inhibited by KN62 (1-[N,O-bis(5-isoquinolinesulphonyl)
      N-methyl-L-tyrosyl]-4-phenylpiperazine)] rescues VP gene transcription in the
      presence of TTX. In the absence of TTX, these independent pathways appear to act
      in a cooperative manner to generate the circadian peak of VP gene transcription
      in the SCN.

PMID- 17202482
TI  - Prenatal exposure to cocaine produces unique developmental and long-term adaptive
      changes in dopamine D1 receptor activity and subcellular distribution.
AB  - Low-dose intravenous cocaine administration to pregnant rabbits causes permanent
      structural alterations in dopamine-rich cerebral cortical areas, substantially
      reduced dopamine D1 receptor coupling to G(s)-protein, and deficits in cognitive
      function. The developmental influences of reduced D1-G(s) coupling and the
      underlying cellular basis are unknown. Using primary neuronal cultures derived
      from the medial frontal cortex and striatum of in utero saline- and cocaine
      exposed embryos, spontaneous neurite outgrowth of in utero-exposed cortical
      neurons was greater than in control neurons. In contrast, striatal neurons
      exposed to cocaine in utero exhibited an entirely opposite adaptive response,
      with diminished spontaneous neurite outgrowth compared with saline-exposed
      controls. Control neurons isolated from the two structures also exhibited
      opposite regulatory responses to the D1 receptor agonist SKF38393 (1-phenyl-2,3,4
      5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride), inhibiting outgrowth in
      cortical cultures and stimulating outgrowth in striatal cultures. The agonist was
      ineffective in modulating neurite outgrowth of neurons from either structure
      isolated from cocaine-exposed fetuses, reflecting the reduced D1-Gs coupling.
      Total D1 receptor number was indistinguishable in neurons from the cocaine- and
      saline-exposed animals, but cell imaging and receptor binding of differentially
      isolated membranes showed that the lack of responsiveness was because of greatly
      reduced cell-surface localization of D1 receptors. These data suggest that
      prenatal exposure to cocaine causes a novel, long-lasting adaptive response in
      the subcellular distribution of D1 receptors, resulting in alterations in
      signaling capacity that have developmental and behavioral consequences.

PMID- 17202483
TI  - Facilitation of extinction learning for contextual fear memory by PEPA: a
      potentiator of AMPA receptors.
AB  - Contextual fear memory is attenuated by the re-exposure of mice to the context
      without aversive stimulus. This phenomenon is called extinction. Here, we report
      that a potentiator of AMPA receptors, 4-[2-(phenylsulfonylamino)ethylthio]-2,6
      difluorophenoxyacetamide (PEPA), potently facilitates extinction learning in
      mice. C57BL/6J mice were exposed to novel context and stimulated by electrical
      footshock. After 24 h (extinction training) and 72 h (extinction test), the mice
      were repeatedly exposed to the context without footshock and the duration of
      their freezing response was measured. The duration of freezing response in the
      extinction test was consistently shorter than the value in extinction training.
      Intraperitoneal injection of PEPA 15 min before extinction training remarkably
      reduced the duration of freezing responses during the extinction training and
      test, compared with the vehicle-injected control mice. This action of PEPA on
      extinction was dose-dependent and inhibited by NBQX (1,2,3,4-tetrahydro-6-nitro
      2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide), an AMPA receptor antagonist. PEPA
      had no effect on acquisition and consolidation of fear memory itself.
      Electrophysiological studies suggested that PEPA activates the neural network
      much more potently in the medial prefrontal cortex (mPFC) than in the basolateral
      amygdala and hippocampal CA1 field. Quantitative PCR studies suggested the
      pronounced expression of PEPA-preferring AMPA receptor subunits (GluR3 and GluR4)
      and a splice variant (flop) in the mPFC. An intra-mPFC injection of PEPA
      facilitated the extinction much more potently than an intra-amygdala injection of
      PEPA did. These results suggest that PEPA facilitates extinction learning through
      AMPA receptor activation mainly in the mPFC.

PMID- 17202484
TI  - Cortical modulation of spatial and angular tuning maps in the rat thalamus.
AB  - The massive feedback projections from cortex to the thalamus modulate sensory
      information transmission in many ways. We investigated the role of
      corticothalamic feedback projections on the directional selectivity (angular
      tuning) of neurons in the rat ventral posterior medial (VPM) nucleus to
      stimulation of their principal whisker. The angular tuning properties of single
      VPM neurons were compared before and after epochs of electrical stimulation of
      layer VI feedback neurons in the ipsilateral cortex under urethane anesthesia.
      Microstimulation of layer VI in "matched" (homologous) barrel columns sharpens
      the angular tuning curves of single VPM neurons that are tuned to the same
      direction as the stimulation site in the cortex. Further, microstimulation
      rotates the angular preference of VPM neurons initially tuned to a different
      direction toward the direction that cortical neurons prefer. Stimulation in
      "mismatched" (nonhomologous) barrel columns suppresses responses without
      consistent effects on angular tuning. We conclude that the primary sensory cortex
      exerts a significant influence on both spatial and angular tuning maps in the
      relay nuclei that project to it. The results suggest that the tuning properties
      of VPM cells in the behaving animal are continually modified to optimize
      perception of the most salient incoming messages.

PMID- 17202485
TI  - Critical period window for spectral tuning defined in the primary auditory cortex
      (A1) in the rat.
AB  - Experience-dependent plasticity during development results in the emergence of
      highly adapted representations of the external world in the adult brain. Previous
      studies have convincingly shown that the primary auditory cortex (A1) of the rat
      possesses a postnatal period of sensory input-driven plasticity but its precise
      timing (onset, duration, end) has not been defined. In the present study, we
      examined the effects of pure-tone exposure on the auditory cortex of developing
      rat pups at different postnatal ages with a high temporal resolution. We found
      that pure-tone exposure resulted in profound, persistent alterations in sound
      representations in A1 only if the exposure occurred during a brief period
      extending from postnatal day 11 (P11) to P13. We also found that postnatal sound
      exposure in this epoch led to striking alterations in the cortical representation
      of sound intensity.

PMID- 17202486
TI  - RalA and RalB function as the critical GTP sensors for GTP-dependent exocytosis.
AB  - Although it has been established that the activation of GTPases by non
      hydrolyzable GTP stimulates neurotransmitter release from many different
      secretory cell types, the underlying mechanisms remain unclear. In the present
      study we aimed to elucidate the functional role(s) for endogenous Ras-like
      protein A (RalA) and RalB GTPases in GTP-dependent exocytosis. For this purpose
      stable neuroendocrine pheochromocytoma 12 (PC12) cell lines were generated in
      which the expressions of both RalA and RalB were strongly downregulated. In these
      double knock-down cells GTP-dependent exocytosis was reduced severely and was
      restored after the expression of RalA or RalB was reintroduced by transfection.
      In contrast, Ca2+-dependent exocytosis and the docking of dense core vesicles
      analyzed by electron microscopy remained unchanged in the double knock-down
      cells. Furthermore, the transfected RalA and RalB appeared to be localized
      primarily on the dense core vesicles in undifferentiated and nerve growth factor
      differentiated PC12 cells. Our results indicate that endogenous RalA and RalB
      function specifically as GTP sensors for the GTP-dependent exocytosis of dense
      core vesicles, but they are not required for the general secretory pathways,
      including tethering of vesicles to the plasma membrane and Ca2+-dependent
      exocytosis.

PMID- 17202487
TI  - Nonredundant role of Akt2 for neuroprotection of rod photoreceptor cells from
      light-induced cell death.
AB  - The Akt kinases mediate cell survival through phosphorylation and inactivation of
      apoptotic machinery components. Akt signaling provides a trophic signal for
      transformed retinal neurons in culture, but the in vivo role of Akt activity is
      unknown. In this study, we found that all three Akt isoforms were expressed in
      rod photoreceptor cells. We investigated the functional roles of Akt1 and Akt2,
      two of the isoforms of Akt, and their biological significance in light-induced
      retinal degeneration. Consistent with the hypothesis that Akt activity is
      important to circumvent stress-induced apoptosis, herein we report the novel
      finding that rod photoreceptor cells in Akt2 knock-out mice exhibited a
      significantly greater sensitivity to stress-induced cell death than rods in
      heterozygous or wild-type mice. Under similar conditions, Akt1 deletion had no
      effect on the retina. The presence of three Akt isoforms in the retina is
      suggestive of a functional redundancy; however, our studies clearly demonstrate
      that, under stress, Akt1 and Akt3 cannot complement the specific survival signals
      driven by Akt2. Furthermore, we show that Akt2 is specially activated is response
      to light stress. The results presented in this study provide the first direct
      evidence that Akt2 has a nonredundant neuroprotective role in photoreceptor
      survival and maintenance.

PMID- 17202488
TI  - Potentiation of exocytosis by phospholipase C-coupled G-protein-coupled receptors
      requires the priming protein Munc13-1.
AB  - The vesicle priming protein Munc13-1 is regulated by diacylglycerol (DAG) and is
      therefore hypothesized to play a role in the control of neurotransmitter release
      by phospholipase C (PLC)-coupled receptors. We combined voltage-clamp recordings
      of voltage-gated Ca2+ channels (VGCCs) and high-resolution capacitance
      measurements to investigate the mechanism of receptor-mediated modulation of
      exocytosis in bovine chromaffin cells. Activation of endogenous H1 G(q)-protein
      coupled receptors (G(q)PCRs) by histamine potentiated stimulus-coupled secretion
      despite concurrently inhibiting Ca2+ influx through VGCCs. Histamine increased
      the size of the readily releasable pool of vesicles and in particular a subpool
      of fusion-competent vesicles localized in close proximity to VGCCs.
      Pharmacological characterization showed that potentiation of exocytosis depended
      on the activation of PLC but not protein kinase C. Overexpression of wild-type
      Munc13-1 by adenoviral infection had no effect on histamine-induced potentiation
      per se, whereas DAG-insensitive Munc13-1(H567K) completely abolished it. This is
      the first endogenous mammalian G(q)PCR signaling pathway identified that engages
      Munc13-1 to increase stimulus-coupled secretion by recruiting vesicles to the
      immediately releasable pool. G(q)PCRs are therefore able to control exocytosis at
      the level of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor) complex formation to produce rapid, short-term potentiation of the
      secretory output of neurons and endocrine cells.

PMID- 17202489
TI  - NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte
      differentiation and myelination.
AB  - Neurons and glia share a mutual dependence in establishing a functional
      relationship, and none is more evident than the process by which axons control
      myelination. Here, we identify LRR and Ig domain-containing, Nogo receptor
      interacting protein (LINGO-1) as a potent axonal inhibitor of oligodendrocyte
      differentiation and myelination that is regulated by nerve growth factor and its
      cognate receptor TrkA in a dose-dependent manner. Whereas LINGO-1 expressed by
      oligodendrocyte progenitor cells was previously identified as an inhibitor of
      differentiation, we demonstrate that axonal expression of LINGO-1 inhibits
      differentiation with equal potency. Disruption of LINGO-1 on either cell type is
      sufficient to overcome the inhibitory action and promote differentiation and
      myelination, independent of axon diameter. Furthermore, these results were
      recapitulated in transgenic mice overexpressing the full length LINGO-1 under the
      neuronal promoter synapsin. Myelination was greatly inhibited in the presence of
      enforced axonal LINGO-1. The implications of these results relate specifically to
      the development of potential therapeutics targeting extrinsic growth factors that
      may regulate the axonal expression of modulators of oligodendrocyte development.

PMID- 17202490
TI  - Functional magnetic resonance imaging investigation of overlapping lateral
      occipitotemporal activations using multi-voxel pattern analysis.
AB  - Several functional areas are proposed to reside in human lateral occipitotemporal
      cortex, including the motion-selective human homolog of macaque area MT (hMT),
      object-form-selective lateral occipital complex (LO), and body-selective
      extrastriate body area (EBA). Indeed, several functional magnetic resonance
      imaging (fMRI) studies have reported significant activation overlap among these
      regions. The standard interpretation of this overlap would be that the common
      areas of activation reflect engagement of common neural systems. Alternatively,
      motion, object form, and body form may be processed independently within this
      general region. To distinguish these possibilities, we first analyzed the lateral
      occipitotemporal responses to motion, objects, bodies, and body parts with whole
      brain group-average analyses and within-subjects functional region of interest
      (ROI) analyses. The activations elicited by these stimuli, each relative to a
      matched control, overlapped substantially in the group analysis. When hMT, LO,
      and EBA were defined functionally within subjects, each ROI in each hemisphere
      (except right-hemisphere hMT) showed significant selectivity for motion, intact
      objects, bodies, and body parts, although only the peak voxel of each region was
      tested. In contrast, multi-voxel analyses of variations in selectivity patterns
      revealed that visual motion, object form, and the form of the human body elicited
      three relatively independent patterns of fMRI activity in lateral
      occipitotemporal cortex. Multi-voxel approaches, in contrast to other methods,
      can reveal the functional significance of overlapping fMRI activity in
      extrastriate cortex and, by extension, elsewhere in the brain.

PMID- 17202491
TI  - The Ca2+-activated K+ channel KCNN4/KCa3.1 contributes to microglia activation
      and nitric oxide-dependent neurodegeneration.
AB  - Brain damage and disease involve activation of microglia and production of
      potentially neurotoxic molecules, but there are no treatments that effectively
      target their harmful properties. We present evidence that the small-conductance
      Ca2+/calmodulin-activated K+ channel KCNN4/ KCa3.1/SK4/IK1 is highly expressed in
      rat microglia and is a potential therapeutic target for acute brain damage. Using
      a Transwell cell-culture system that allows separate treatment of the microglia
      or neurons, we show that activated microglia killed neurons, and this was
      markedly reduced by treating only the microglia with a selective inhibitor of
      KCa3.1 channels, triarylmethane-34 (TRAM-34). To assess the role of KCa3.1
      channels in microglia activation and key signaling pathways involved, we
      exploited several fluorescence plate-reader-based assays. KCa3.1 channels
      contributed to microglia activation, inducible nitric oxide synthase
      upregulation, production of nitric oxide and peroxynitrite, and to consequent
      neurotoxicity, protein tyrosine nitration, and caspase 3 activation in the target
      neurons. Microglia activation involved the signaling pathways p38 mitogen
      activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB), which are
      important for upregulation of numerous proinflammatory molecules, and the KCa3.1
      channels were functionally linked to activation of p38 MAPK but not NF-kappaB.
      These in vitro findings translated into in vivo neuroprotection, because we found
      that degeneration of retinal ganglion cells after optic nerve transection was
      reduced by intraocular injection of TRAM-34. This study provides evidence that
      KCa3.1 channels constitute a therapeutic target in the CNS and that inhibiting
      this K+ channel might benefit acute and chronic neurodegenerative disorders that
      are caused by or exacerbated by inflammation.

PMID- 17202493
TI  - Beta/gamma oscillatory activity in the CA3 hippocampal area is depressed by
      aberrant GABAergic transmission from the dentate gyrus after seizures.
AB  - Oscillatory activity in the CA3 region is thought to be involved in the encoding
      and retrieval of information. These oscillations originate from the recurrent
      excitation between pyramidal cells that are entrained by the synchronous rhythmic
      inhibition of local interneurons. We show here that, after seizures, the dentate
      gyrus (DG) tonically inhibits beta/gamma (20-24 Hz) field oscillations in the CA3
      area through GABA-mediated signaling. These oscillations originate in the
      interneuron network because they are maintained in the presence of ionotropic
      glutamate receptor antagonists, and they can be blocked by GABA(A) receptor
      antagonists or by perfusion of a calcium-free extracellular medium. Inhibition of
      this oscillatory activity requires intact DG-to-CA3 connections, and it is
      suppressed by the activation of metabotropic glutamate receptors (mGluR). The
      influence of mGluR activation was reflected in the spontaneous subthreshold
      membrane oscillations of CA3 interneurons after one seizure but could also be
      observed in pyramidal cells after several seizures. Coincident stimulation of the
      DG at and beta/gamma frequencies produced a frequency-dependent excitation of
      interneurons and the inhibition of pyramidal cells. Indeed, these effects were
      maximal at the frequency that matched the mGluR-sensitive spontaneous field
      oscillations, suggesting a resonance phenomenon. Our results shed light on the
      mechanisms that may underlie the deficits in memory and cognition observed after
      epileptic seizures.

PMID- 17202494
TI  - Serum gamma-glutamyltransferase and risk of disease.

PMID- 17202492
TI  - Previous cocaine exposure makes rats hypersensitive to both delay and reward
      magnitude.
AB  - Animals prefer an immediate over a delayed reward, just as they prefer a large
      over a small reward. Exposure to psychostimulants causes long-lasting changes in
      structures critical for this behavior and might disrupt normal time-discounting
      performance. To test this hypothesis, we exposed rats to cocaine daily for 2
      weeks (30 mg/kg, i.p.). Approximately 6 weeks later, we tested them on a variant
      of a time-discounting task, in which the rats responded to one of two locations
      to obtain reward while we independently manipulated the delay to reward and
      reward magnitude. Performance did not differ between cocaine-treated and saline
      treated (control) rats when delay lengths and reward magnitudes were equal at the
      two locations. However, cocaine-treated rats were significantly more likely to
      shift their responding when we increased the delay or reward size asymmetrically.
      Furthermore, they were slower to respond and made more errors when forced to the
      side associated with the lower value. We conclude that previous exposure to
      cocaine makes choice behavior hypersensitive to differences in the time to and
      size of available rewards, consistent with a general effect of cocaine exposure
      on reward valuation mechanisms.

PMID- 17202495
TI  - Evolving paradigms of clinical pathology resident education and consultation.

PMID- 17202496
TI  - Lipocalins and insulin resistance: etiological role of retinol-binding protein 4
      and lipocalin-2?

PMID- 17202497
TI  - Innate immune response by ficolin binding in apoptotic placenta is associated
      with the clinical syndrome of preeclampsia.
AB  - BACKGROUND: Unidentified circulating factors derived from placenta are thought to
      be responsible for the exaggerated systemic inflammation leading to preeclampsia.
      Our aim was to identify the circulating factors present in preeclampsia and to
      investigate their relationship to the underlying systemic immune response
      responsible for the associated clinical manifestations. METHODS: We obtained
      blood samples from pregnant women with and without preeclampsia and performed
      comparative proteomic analyses to identify the abnormal circulating factors by 2
      dimensional polyacrylamide gel electrophoresis and matrix-assisted laser
      desorption ionization time of flight for protein separation and identification.
      In placentas from preeclamptic pregnancies, we evaluated the potential role of
      the candidate proteins identified by Western and immunohistochemical analysis. We
      also used proinflammatory cytokine antibody arrays to investigate local and
      systemic immune responses. RESULTS: We found that ficolins, the pattern
      recognition proteins involved in the lectin-complement pathway, were
      differentially expressed in plasma from preeclamptic pregnancies. Ficolins were
      present in low concentrations in plasma but at high concentrations in the
      placenta, particularly in syncytiotrophoblasts undergoing apoptosis. The binding
      of ficolins in apoptotic trophoblasts induced innate immunity through local and
      systemic cytokine activation and correlated with the clinical manifestation of
      preeclampsia. CONCLUSIONS: We identified specific in vivo circulating factors
      derived from the placenta that are responsible for the local immune recognition
      and systemic inflammatory response in the development of clinical manifestations
      of preeclampsia. These findings may have predictive value and also therapeutic
      applications to lessen adverse clinical outcomes of preeclampsia.

PMID- 17202498
TI  - Mass spectrometric detection of an SNP panel as an internal positive control for
      fetal DNA analysis in maternal plasma.

PMID- 17202499
TI  - Hemoglobin constant spring can interfere with glycated hemoglobin measurements by
      boronate affinity chromatography.

PMID- 17202500
TI  - To mix with pooled normal plasma or not to mix: a comparative study of 2
      approaches for assessing lupus anticoagulant inhibitory activity in the dilute
      Russell viper venom method.

PMID- 17202501
TI  - Upconversion fluorescence enables homogeneous immunoassay in whole blood.

PMID- 17202502
TI  - A novel proximal -13914G>A base replacement in the vicinity of the common
      13910T/C lactase gene variation results in an atypical LightCycler melting curve
      in testing with the MutaREAL Lactase test.

PMID- 17202503
TI  - Ex vivo simulation of drug action: quantification of drug-induced mRNA as a
      bridge between preclinical and clinical trials.

PMID- 17202504
TI  - Antenatal biochemical expression of cystinuria and relation to fetal
      hyperechogenic colon.

PMID- 17202505
TI  - Instrument comparison for heterozygote scanning of single and double
      heterozygotes: a correction and extension of Herrmann et al., Clin Chem
      2006;52:494-503.

PMID- 17202506
TI  - Detection of monoclonal proteins by capillary zone electrophoresis: comparison of
      2 multichannel automated systems.

PMID- 17202507
TI  - Prolonged frozen storage of urine reduces the value of albuminuria for mortality
      prediction.

PMID- 17202510
TI  - Review of research related to Parse's Theory of Human Becoming.
AB  - Ninety-three retrievable studies guided by the human becoming theory between 1985
      and 2006, are reviewed. A summary of the studies is tabulated according to the
      two basic human becoming research methods, the human becoming applied research
      method, and other qualitative research methods using human becoming as the frame
      of reference. The authors provide an overview of the studies and the human
      becoming research methods and further illuminate the findings of studies reviewed
      under four major themes that describe the phenomena studied.

PMID- 17202509
TI  - Envisioning nursing in 2050 through the eyes of nurse theorists: Leininger and
      Watson.
AB  - Madeleine Leininger and Jean Watson envision how their theoretical ideas will be
      expressed in the world in 2050. Leininger explains how her theory and
      ethnoresearch methodology have given rise to transcultural nursing and the
      culture care nursing paradigm and predicts that they will continue to contribute
      to culturally congruent care practices that promote health, healing, quality of
      life, and even world peace. Watson provides a vision based on an emergent
      perspective that emphasizes subjective dimensions related to self-knowledge, self
      control, self-caring, and self-healing potential; spirit and wholeness of
      being/becoming; natural healing approaches; and caring, healing relationships
      with self and others.

PMID- 17202511
TI  - Information and human freedom: nursing implications and ethical decision-making
      in the 21st century.
AB  - With globalization and the increasing volume of healthcare information available
      to people, questions surface as nurses contemplate and envision what role and how
      our nursing theory-guided discipline ought to be lived with colleagues of other
      disciplines, each other, and those we serve in the 21(st) century. This column
      begins a path of ethical exploration and possible implications for the
      opportunities and challenges associated with the information age in nursing
      research, practice, and education. Discussion focuses on the disciplinary
      responsibilities for information giving and receiving; coming to know, human
      freedom, and decision-making in the human-universe-health process.

PMID- 17202512
TI  - Sea change in nursing.

PMID- 17202513
TI  - Theory-guided evidence-based reflective practice: an orientation to education for
      quality care.

PMID- 17202514
TI  - Picturing the nurse-person/family/community process in the year 2050.
AB  - How will nurses relate with persons in the year 2050? And, how might technology
      enable or limit the nursing process with persons, families, and communities?
      These are the questions addressed in this column. Imaging practice in light of
      the technological imaginings and projections is facilitated by a possible
      scenario that includes robotics that not only monitor human biological processes,
      they also emote compassion and caring that may one day be dosed according to the
      latest diagnostic prescription. Three nurses in this column present their views
      of how nursing might evolve. Karnick, aligned with the human becoming school of
      thought, imagines a practice anchored in respect for humanity and quality of life
      and an accompanying respect for nursing knowledge and nursing work. Senesac and
      Sato, aligned with Roy's adaptation model, call for nurses to envision and choose
      the future they want to have. Clear in both perspectives is a reverence for human
      values and human experience and for the critical role of nursing knowledge as we
      move toward the not-yet of 2050.

PMID- 17202515
TI  - Nursing, healthcare, and culture: views from Canada and Taiwan for the year 2050.
      Interview by Jacqueline Fawcett.
AB  - This column presents a dialogue with Canadian nurse scholar Mireille Lavoie and
      Taiwanese nurse scholar Yea-Ing Lotus Shyu, who share their own vision and their
      understanding of their country's vision of nursing, health-care, and quality of
      life in the year 2050.

PMID- 17202516
TI  - The experience of feeling unsure for women at end-of-life.
AB  - The purpose of this study was to answer the research question, What is the
      structure of the lived experience of feeling unsure? The participants were 9
      women at end-of-life. The Parse research method, a phenomenological- hermeneutic
      method, was used to discover the structure of feeling unsure. Through the process
      of extraction- synthesis three core concepts were identified: disquieting
      apprehensiveness, pressing on, and intimate sorrows. Thus, the lived experience
      of feeling unsure for these 9 women is disquieting apprehensiveness arising while
      pressing on with intimate sorrows. The structure provides knowledge about feeling
      unsure and its connection to health and quality of life. Feeling unsure will be
      discussed in relation to the principles and concepts of human becoming and in
      relation to how it can inform nursing practice and future research.

PMID- 17202517
TI  - The evolution of Rogers' Science of Unitary Human Beings: 21st century
      reflections.
AB  - The purpose of this article is to reflect on the state of Martha E. Rogers'
      science of unitary human beings as it has evolved over the past 40 years, with
      particular attention to the decade since her death. Although Rogers never updated
      her 1970 book, revised concepts and principles of homeodynamics, as reported in
      other publications, are discussed. In more than a decade since Rogers' death,
      nurse scientists have been prolific in explicating the science in scholarly
      research and writing. An example of theories derived from the science, as well as
      concepts under study, and research methods are identified. Twenty-first century
      thoughts on the science of unitary human beings, as expressed by three founders
      of the Society of Rogerian Scholars, are highlighted from an interview conducted
      by Fawcett. Rogers suggested that the development of a science of unitary human
      beings is a never ending process.

PMID- 17202518
TI  - Self-care requirements for activity and rest: an Orem nursing focus.
AB  - According to Orem's self-care deficit nursing theory, helping people to maintain
      a balance between activity and rest (a universal self-care requisite) is a
      legitimate concern of nursing. The meaning of activity and rest, the requirements
      and potential measures for meeting this self-care requisite, and factors that
      might influence the process are explored. Criteria for determining a need for
      nursing, guides for a nursing clinical assessment, and guides for nursing action
      are suggested as potential ways to assist persons to meet the action demands
      associated with this self-care requisite.

PMID- 17202519
TI  - Treating older adults as ends rather than means only.
AB  - The treatment of older adults by nurses requires professional knowledge, skills,
      and attitudes which are carefully thought out and put into practice in
      organizations and societies that do not always respect the perspectives and
      priorities of older adults. McCormack's person-centered nursing with older adults
      approach seeks to help nurses deal with this bind. His approach, as critiqued by
      Landers and McCarthy, is discussed here.

PMID- 17202520
TI  - Person-centered nursing practice with older people in Ireland.
AB  - This column presents an analysis of McCormack's conceptual framework for person
      centered practice with older people as a theoretical basis for the delivery of
      care of older adults in an Irish context. The evaluative process is guided by the
      framework proposed by Fawcett (2000) for the analysis and evaluation of
      conceptual models of nursing. The historical evolution, philosophical claims, and
      an overview of the content of the model are addressed. The following criteria are
      then applied: logical congruence, the generation of the theory, the credibility
      of the model, and the contribution of the model to the discipline of nursing.

PMID- 17202521
TI  - A re-consideration of what constitutes "evidence" in the healthcare professions.
AB  - The dominant discourses surrounding the debate on evidence-based healthcare takes
      for granted that the concept evidence is exclusively derived from randomized
      controlled trials. However, influenced by the experience of practicing
      clinicians, who assert that there are diverse sources of evidence, we contend
      that evidence-based practice can properly be inclusive of diverse forms of
      evidence including the results of all forms of rigorous research, expert opinion,
      and experience. The Joanna Briggs Institute model illustrates this broader
      definition of what counts as evidence which is seen as critical to developing the
      role and use of evidence-based healthcare within the complexity of practice
      settings globally.

PMID- 17202523
TI  - Swazi men's contraceptive knowledge, attitudes, and practices.
AB  - This study investigated Swazi men's contraceptive knowledge, attitudes, and
      practices. Thirty adolescent men, aged from 16 to 18, and 86 adult men from urban
      and rural areas participated in focus group interviews. Adult Swazi men indicated
      that men were the sole decision makers about sexual and reproductive issues. The
      number and gender of children remains socially significant in Swaziland.
      Adolescent men expressed contradictory notions in expecting girls to refuse
      unprotected sex but maintaining that men were the sole decision makers about
      sexual matters. They agreed that women should commence childbearing activities at
      the age of 21 or later. This finding holds some promise for enabling more Swazi
      women to use contraceptives at least until they have completed their schooling.
      Contraceptive services were not readily accessible to men in Swaziland.

PMID- 17202524
TI  - Family and community influences on the social and sexual lives of Latino gay men.
AB  - The purpose of this study was to explore the effect of family and community on
      the social and sexual lives of a group of Latino gay men living in a metropolitan
      area. A secondary analysis of four focus groups with 28 Latino gay men was
      conducted. Families had a difficult time acknowledging and supporting
      participants' homosexuality. Participants experienced racism, discrimination, and
      physical and verbal abuse as a result of their ethnicity and homosexuality. These
      negative effects contributed to their marginalization and made them vulnerable to
      depression and suicide. Health care professionals should be aware of the effect
      of family and culture on the social and sexual lives of Latino gay men so that
      they can intervene and direct the client to the services needed to manage
      depression, suicidal ideation, and high-risk sexual behavior.

PMID- 17202525
TI  - Iron deficiency anemia (IDA) perceptions and dietary iron intake among young
      women and pregnant women in Jordan.
AB  - To determine Iron Deficiency Anemia (IDA) perceptions and iron dietary practices
      of Jordanian female students and pregnant women, a descriptive quantitative
      questionnaire was administered to 271 participants: 206 female students and 65
      pregnant women. This pilot study found that most participants can identify foods
      containing iron, but lack appropriate iron intake, because of eating habits and
      finances; more than 50% report daily symptoms of IDA, including dizziness,
      fatigue, depression, headaches, and loss of concentration and memory. There are
      no statistically significant differences in IDA perceptions and iron-related
      dietary practices based on education, and relatively few based on where
      participants live, their available financial resources, or their position
      (pregnant women or young women). Culturally sensitive intervention research,
      which addresses application of IDA education principles, temporary
      supplementation, and adequate income for dietary modification and long-term iron
      supplementation to prevent IDA is warranted.

PMID- 17202527
TI  - Methods of coping with labor pain used by Jordanian women.
AB  - The purpose of this study is to explore labor pain coping methods among Jordanian
      parturients. Descriptive statistics and content analysis were used to analyze
      data on demographics and coping methods from 100 low-risk parturients who were
      recruited from the postpartum unit in a major hospital in Jordan: Four labor pain
      coping methods that included physiological, psychological, spiritual, and
      cognitive coping were reported. This study confirms previous findings regarding
      coping methods and adds new knowledge on coping with labor pain among Jordanian
      parturients: The significance of childbirth education as a means to inform
      Jordanian women about coping with labor pain is emphasized. This study also
      highlighted the important roles that nurses and midwives can play as educators
      and supporters during pregnancy and labor.

PMID- 17202526
TI  - Mutual caring of elderly Korean couples.
AB  - The article described the experiences of elderly couples caring for each other
      using ethnographic methodology. Ten couples were interviewed in depth. The
      presence of a support system was found to be the primary requirement of elderly
      couples. Three taxonomies comprised the support system: (a) desire for respect in
      care, (b) desire for reliance, and (c) expectation. The close linkage and
      interaction of desire for care, desire for reliance, and expectations were
      confirmed. The findings suggested establishing a holistic support network for
      these elders.

PMID- 17202528
TI  - Women's stories of abortion in southern Gabon, Africa.
AB  - The purpose of this study was to explore the reasons women in rural, southern
      Gabon, Africa, chose to terminate their pregnancies, the methods used to induce
      abortions, and postabortion effects experienced by these women. Abortion is
      illegal in this country. A descriptive qualitative design guided the methodology
      for this study. Five women with a history of induced abortion were interviewed in
      depth for their abortion story. Reasons cited for an abortion included lack of
      financial and partner support. Abortion methods included oral, rectal, and
      vaginal concoctions of leaves, bark, and water and over-the-counter medications,
      including misoprostol. Affects were physical, spiritual, and relational. Health
      care professionals need to provide women with guidance for appropriate
      contraceptive usage. Abortion after-care of women with physical and spiritual
      needs is important. Future research is suggested on the use of misoprostol in
      Gabon to understand its affects on women's reproductive health.

PMID- 17202529
TI  - Contextual empowerment: the impact of Health Brigade involvement on the women of
      Miraflor, Nicaragua.
AB  - This qualitative, descriptive study investigated how working with Health Brigades
      influenced a sense of empowerment and a resultant shifting of gender-power
      relationships for women in a rural Nicaraguan community. A convenience sample of
      10 women aged 18 to 65 years who had worked with the Brigades were interviewed.
      Open and axial coding were used to determine core categories and theoretical
      concepts. From this emerged a grounded theory of contextual empowerment. Key
      findings included that within this collectivist culture, the concept of
      contextual empowerment includes psychosocial and structural dimensions.
      Implications for nursing practice include the impact of unintentional role
      modeling.

PMID- 17202530
TI  - Teaching methods and an outcome tool for measuring cultural sensitivity in
      undergraduate nursing students.
AB  - A major challenge facing the nursing profession is to educate and assist nurses
      to develop the skills to provide culturally relevant care. This article describes
      one school's multicultural curriculum for baccalaureate nursing students and a
      tool to measure changes in behaviors and attitudes. The article presents the
      psychometric properties of the Cross-Cultural Evaluation Tool that yields a cross
      cultural interaction score. Successful teaching strategies are presented that are
      substantiated by increased student cross-cultural interaction score scores.

PMID- 17202531
TI  - Yemeni families and child lead screening in Detroit.
AB  - This project was an exploratory effort to screen and treat immigrant Yemeni
      children who were at high risk for lead poisoning. The Detroit metropolitan area
      is home to the largest number of Arabic immigrants in the United States. In
      addition, Detroit has the largest rate of childhood lead poisoning in the state
      of Michigan. No published studies were found that explored the prevalence of lead
      poisoning among Yemeni children in Michigan. Immigrant children from countries
      where knowledge of lead poisoning is limited may be particularly vulnerable
      because of difficulties in language and accessing health care. Children's
      Hospital of Michigan CATCH School Mobile Health Center conducted this health
      screening project. This article reports on the gender and health issues
      encountered during the community outreach lead testing effort within a Yemeni
      neighborhood in Detroit.

PMID- 17202532
TI  - Practical strategies for providing culturally sensitive, ethical care in
      developing nations.
AB  - Providing health care in developing nations results in cultural and ethical
      challenges for health care professionals. The authors' intent is to raise
      readers' awareness of how to maintain an ethical and culturally sensitive
      approach to practice in developing nations. Four practical approaches to ethical
      decision-making, developed from the literature and praxis, in conjunction with
      traditional moral theory and guidelines from professional and international
      organizations are discussed. Ethical multiculturalism, a view that combines
      universalism and multiculturalism undergirds culturally appropriate and ethically
      responsive decisions.

PMID- 17202533
TI  - Unmet need for services and interventions among adolescents with mental
      disorders.

PMID- 17202534
TI  - To do or not to do? The complexities of addiction, motivation, self-control, and
      impulsivity.

PMID- 17202535
TI  - Randomized controlled trials and psychotherapy research.

PMID- 17202536
TI  - Eating disorders and coercion.

PMID- 17202537
TI  - Inhibition and timing in cortical neural circuits.

PMID- 17202538
TI  - How and why genetic linkage has not solved the problem of psychosis: review and
      hypothesis.
AB  - OBJECTIVE: The author examined the chromosomal linkage method as an approach to
      the genetic basis of schizophrenia and bipolar disorder. METHOD: Comparisons were
      conducted of recent meta-analyses of genome scans of schizophrenia and bipolar
      disorder and of the three largest (N>300) sibling pair studies of schizophrenia
      and schizoaffective disorder and a comparable study of bipolar illness. RESULTS:
      Recent meta-analyses have not identified consistent sites of linkage. The three
      largest studies of schizophrenia fail to agree on a single locus, no commonality
      with bipolar illness has been demonstrated, and there is no replicable support
      for any of the current candidate genes. DISCUSSION: An alternative to the concept
      that DNA sequence variation lies in "multiple genes of small effect" is the
      hypothesis that the variation is epigenetic but related to the genetic transition
      ("the speciation event") that separated Homo sapiens from a prior hominid
      species. This hypothesis draws attention to the chromosomal rearrangement (the
      Xq21.3/Yp translocation) that occurred some 6 million years ago in the hominid
      lineage and subsequent rearrangements, including a paracentric inversion, that
      have taken place within the translocated segment. Here it is argued that the most
      recent of these events is relevant to specifically human characteristics,
      including language. The gene pair protocadherin X and Y within this region is
      under new selective pressure and is in a novel (epigenetic) situation with
      respect to X inactivation. CONCLUSIONS: Epigenetic variation associated with
      chromosomal rearrangements that occurred in the hominid lineage and that relates
      to the evolution of language could account for predisposition to schizophrenia
      and schizoaffective and bipolar disorder and failure to detect such variation by
      standard linkage approaches.

PMID- 17202539
TI  - Understanding and ameliorating revenge fantasies in psychotherapy.

PMID- 17202540
TI  - Sadness and loss: toward a neurobiopsychosocial model.

PMID- 17202541
TI  - Julius Ludwig August Koch (1841-1908).

PMID- 17202542
TI  - Service costs of caring for adolescents with mental illness in a rural community,
      1993-2000.
AB  - OBJECTIVE: Costs of treating child psychiatric disorders fall on educational,
      primary care, juvenile justice, and social service agencies as well as on
      psychiatric services. The authors estimated multiagency mental health costs by
      integrating service unit costs with utilization rates in an 11-county area. Using
      psychiatric diagnoses made independently of service use records, the authors
      calculated costs across agencies as well as the extent of unmet need for
      psychiatric care. METHOD: Annual parent and child reports were used to measure
      mental health care needs and units of service across 21 types of settings for the
      population-based Great Smoky Mountain Study sample of 1,420 adolescents from ages
      13 to 16. Unit costs for services were generated from information from service
      providers and records. The authors calculated costs overall, costs by type of
      service, and costs by diagnosis. RESULTS: Average annual costs per adolescent
      treated were $3,146. Juvenile justice and inpatient/residential facilities
      accounted for well over half of the total costs. Costs for youths with two or
      more diagnoses were twice as much as costs of those with a single disorder. Among
      adolescents with service needs, 66.9% received no services. Public health
      insurance was associated with higher rates of specialty mental health care than
      either private insurance or no insurance. CONCLUSIONS: Annual costs across all
      services were three to four times greater than recent health insurance estimates
      alone. Many costs for adolescents with mental health problems were borne by
      agencies not designed primarily to provide psychiatric or psychological services.
      Only one in three adolescents needing psychiatric care received any mental health
      services.

PMID- 17202544
TI  - Neural circuitry engaged during unsuccessful motor inhibition in pediatric
      bipolar disorder.
AB  - OBJECTIVE: Deficits in motor inhibition may contribute to impulsivity and
      irritability in children with bipolar disorder. Studies of the neural circuitry
      engaged during failed motor inhibition in pediatric bipolar disorder may increase
      our understanding of the pathophysiology of the illness. The authors tested the
      hypothesis that children with bipolar disorder and comparison subjects would
      differ in ventral prefrontal cortex, striatal, and anterior cingulate activation
      during unsuccessful motor inhibition. They also compared activation in medicated
      versus unmedicated children with bipolar disorder and in children with bipolar
      disorder and attention deficit hyperactivity disorder (ADHD) versus those with
      bipolar disorder without ADHD. METHOD: The authors conducted an event-related
      functional magnetic resonance imaging study comparing neural activation in
      children with bipolar disorder and healthy comparison subjects while they
      performed a motor inhibition task. The study group included 26 children with
      bipolar disorder (13 unmedicated and 15 with ADHD) and 17 comparison subjects
      matched by age, gender, and IQ. RESULTS: On failed inhibitory trials, comparison
      subjects showed greater bilateral striatal and right ventral prefrontal cortex
      activation than did patients. These deficits were present in unmedicated
      patients, but the role of ADHD in mediating them was unclear. CONCLUSIONS: In
      relation to comparison subjects, children with bipolar disorder may have deficits
      in their ability to engage striatal structures and the right ventral prefrontal
      cortex during unsuccessful inhibition. Further research should ascertain the
      contribution of ADHD to these deficits and the role that such deficits may play
      in the emotional and behavioral dysregulation characteristic of bipolar disorder.

PMID- 17202543
TI  - Is decreased prefrontal cortical sensitivity to monetary reward associated with
      impaired motivation and self-control in cocaine addiction?
AB  - OBJECTIVE: This study attempted to examine the brain's sensitivity to monetary
      rewards of different magnitudes in cocaine abusers and to study its association
      with motivation and self-control. METHOD: Sixteen cocaine abusers and 13 matched
      healthy comparison subjects performed a forced-choice task under three monetary
      value conditions while brain activation was measured with functional magnetic
      resonance imaging. Objective measures of state motivation were assessed by
      reaction time and accuracy, and subjective measures were assessed by self-reports
      of task engagement. Measures of trait motivation and self-control were assessed
      with the Multidimensional Personality Questionnaire. RESULTS: The cocaine abusers
      demonstrated an overall reduced regional brain responsivity to differences
      between the monetary value conditions. Also, in comparison subjects but not in
      cocaine abusers, reward-induced improvements in performance were associated with
      self-reports of task engagement, and money-induced activations in the lateral
      prefrontal cortex were associated with parallel activations in the orbitofrontal
      cortex. For cocaine abusers, prefrontal cortex sensitivity to money was instead
      associated with motivation and self-control. CONCLUSIONS: These findings suggest
      that in cocaine addiction 1) activation of the corticolimbic reward circuit to
      gradations of money is altered; 2) the lack of a correlation between objective
      and subjective measures of state motivation may be indicative of disrupted
      perception of motivational drive, which could contribute to impairments in self
      control; and 3) the lateral prefrontal cortex modulates trait motivation and
      deficits in self-control, and a possible underlying mechanism may encompass a
      breakdown in prefrontal-orbitofrontal cortical communication.

PMID- 17202545
TI  - Independent domains of inhibitory gating in schizophrenia and the effect of
      stimulus interval.
AB  - OBJECTIVE: Patients with schizophrenia are known to have inhibitory gating
      deficits in the suppression of evoked potential P50 response to repeated stimuli
      and the prepulse inhibition of the startle response. In the current study, the
      authors aimed to determine whether these two inhibitory gating measures are
      related in schizophrenia patients or whether abnormal P50 suppression and
      abnormal prepulse inhibition are independent neurophysiological characteristics
      of schizophrenia. The authors hypothesized that the relationship of the two
      measures may vary as a function of interstimulus intervals of stimulus
      presentations. METHOD: Fifty-nine schizophrenia patients and 17 healthy
      comparison subjects were tested on both P50 suppression and prepulse inhibition.
      P50 suppression was measured using paired clicks with 500-msec interstimulus
      intervals. Prepulse inhibition was measured by using a series of prepulse-pulse
      pairs with interstimulus intervals ranging from 30 to 500 msec. RESULTS: Patients
      showed reduced P50 suppression and prepulse inhibition in relation to healthy
      comparison subjects. Concordance analysis showed that abnormal P50 suppression
      and abnormal prepulse inhibition do not necessarily occur together. Prepulse
      inhibition was most prominent at the 120-msec interstimulus interval, which was
      not correlated to P50 suppression. At the 500-msec interstimulus interval,
      prepulse inhibition was significantly but negatively correlated to P50
      suppression. Prepulse inhibition at the other interstimulus intervals was not
      correlated with P50 suppression. CONCLUSIONS: These neurophysiological measures
      lack robust and direct relationships and likely mark independent aspects of
      abnormal brain inhibitory functions in schizophrenia.

PMID- 17202546
TI  - Risk-taking behaviors among Israeli adolescents exposed to recurrent terrorism:
      provoking danger under continuous threat?
AB  - OBJECTIVE: This study aimed to assess 1) the relationship between risk-taking
      behaviors and exposure to terrorism, 2) the relationship between posttraumatic
      symptoms and risk-taking behaviors, and 3) gender differences in the type and
      frequency of risk-taking behaviors and their differential associations with
      posttraumatic symptoms. METHOD: The participants were 409 Israeli adolescents 15
      to 18 years of age. Exposure to terrorism was assessed with a questionnaire
      developed specifically for the Israeli security situation. Posttraumatic symptoms
      were measured with the University of California at Los Angeles Reaction Index.
      Functional impairment was measured with the Diagnostic Interview Schedule for
      Children. Risk-taking behavior-and the adolescents' perceptions of such behavior
      was assessed with a self-report questionnaire. RESULTS: Israeli adolescents
      exposed to continuous threats of terrorist attacks reported high levels of risk
      taking behaviors. The severity of risk-taking was associated with greater
      terrorism exposure. Adolescents suffering from posttraumatic symptoms reported
      more risk-taking behaviors than nonsymptomatic adolescents. Although there was no
      gender difference in the degree of exposure to terrorism, boys reported taking
      more risks than girls. The association between posttraumatic symptoms and risk
      taking behaviors was stronger in boys than girls. Functional impairment, gender,
      avoidance symptoms, level of exposure, and degree of fear predicted the severity
      of risk-taking behaviors. CONCLUSIONS: Clinicians and educators should be aware
      of the strong link between posttraumatic distress and risk-taking behaviors. Risk
      taking behaviors may be a manifestation of functional impairment and
      posttraumatic distress, especially for boys exposed to terrorism.

PMID- 17202547
TI  - A randomized, controlled trial with 6-month follow-up of repetitive transcranial
      magnetic stimulation and electroconvulsive therapy for severe depression.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has been reported
      to be as effective as electroconvulsive therapy (ECT) for major depression. The
      authors conducted a multicenter randomized, controlled trial to test the
      equivalence of rTMS with ECT. METHOD: Forty-six patients with major depression
      referred for ECT were randomly assigned to either a 15-day course of rTMS of the
      left dorsolateral prefrontal cortex (N=24) or a standard course of ECT (N=22).
      The primary outcome measures were the score on the 17-item Hamilton Depression
      Rating Scale (HAM-D) and the proportion of patients with remissions (Hamilton
      score, <or=8) at the end of treatment. Secondary outcomes included mood self
      ratings on the Beck Depression Inventory-II and visual analogue mood scales,
      Brief Psychiatric Rating Scale (BPRS) score, and both self-reported and observer
      rated cognitive changes. The patients were followed up after 6 months. RESULTS:
      HAM-D scores at the end of treatment were significantly lower for ECT, with 13
      patients (59.1%) achieving remission in the ECT group and four (16.7%) in the
      rTMS group. However, at 6 months the HAM-D scores did not differ between groups.
      Beck scale, visual analogue mood scale, and BPRS scores were lower for ECT at the
      end of treatment and remained lower after 6 months. Self- and observer-rated
      cognitive measures were similar in the two groups. CONCLUSIONS: rTMS was not as
      effective as ECT, and ECT was substantially more effective for the short-term
      treatment of depression.

PMID- 17202548
TI  - Treatment of acute posttraumatic stress disorder with brief cognitive behavioral
      therapy: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of brief
      cognitive behavioral therapy for patients with acute posttraumatic stress
      disorder (PTSD) resulting from various types of psychological trauma. METHOD: The
      authors randomly assigned 143 patients with acute PTSD (irrespective of the time
      criterion), within 3 months after experiencing a traumatic incident, to either
      brief cognitive behavioral therapy (N=79) or a waiting list comparison group
      (N=64). Cognitive behavioral therapy consisted of four weekly sessions containing
      education, relaxation exercises, imaginal exposure, in vivo exposure, and
      cognitive restructuring. Main outcome measure was PTSD score measured by
      structured interview; secondary outcomes were anxiety and depression measured by
      questionnaire. Assessments took place before the intervention and 1 week and 4
      months after the intervention. RESULTS: Symptoms of PTSD, anxiety, and depression
      decreased in both groups over time. One week after the intervention, the
      cognitive behavioral therapy group had significantly fewer symptoms of PTSD than
      the comparison group, but this difference was smaller and no longer significant 4
      months after the intervention. Similar results were found for anxiety and
      depression scores. Subgroup analyses showed that cognitive behavioral therapy led
      to significantly lower PTSD scores at 4 months in patients with baseline comorbid
      major depression and in patients who were included within the first month after
      the traumatic incident both at 1 week and at 4 months. CONCLUSIONS: Brief early
      cognitive behavioral therapy accelerated recovery from symptoms of acute PTSD but
      did not influence long-term results. Brief early cognitive behavioral therapy
      showed enhanced efficacy in patients with baseline comorbid depression and
      patients who were included within 1 month after their traumatic experience.

PMID- 17202549
TI  - Cognitive behavior therapy and paroxetine in the treatment of hypochondriasis: a
      randomized controlled trial.
AB  - OBJECTIVE: This study, to the authors' knowledge, is the first randomized
      controlled trial comparing the efficacy of cognitive behavior therapy (CBT),
      paroxetine, and a placebo (administered in a double blind fashion) in the
      treatment of hypochondriasis. METHOD: The authors randomly assigned 112 subjects
      with hypochondriasis according to DSM-IV criteria to 16 weeks of outpatient
      treatment with CBT, paroxetine, or a placebo. The main outcome measure was the
      Whiteley Index. The authors made pretest and posttest assessments and analyzed
      all outcome measures using a General Linear Model 3x2 repeated measures analysis
      of variance with Helmert contrasts. The authors considered subjects who scored at
      least one standard deviation below the mean pretest score on the Whiteley Index
      as responders. All analyses were conducted on intent-to-treat and completer
      bases. RESULTS: On the Whiteley Index, Helmert contrasts on the intent-to-treat
      and completer cohorts revealed that pooled CBT and paroxetine were significantly
      superior to placebo, but did not differ significantly from each other. The
      responder analysis on the intent-to-treat cohort and completer cohort,
      respectively, revealed the following percentages of responders per group: CBT
      group, 45% and 54%; paroxetine group, 30% and 38%; and placebo group, 14% and
      12%. In the intent-to-treat analysis, only CBT differed significantly from the
      placebo. In the completer analysis, both paroxetine and CBT differed
      significantly from the placebo. CONCLUSIONS: CBT or paroxetine are effective
      short-term treatment options for subjects with hypochondriasis.

PMID- 17202550
TI  - A randomized trial of integrated group therapy versus group drug counseling for
      patients with bipolar disorder and substance dependence.
AB  - OBJECTIVE: Although bipolar disorder and substance use disorder frequently co
      occur, there is little information on the effectiveness of behavioral treatment
      for this population. Integrated group therapy, which addresses the two disorders
      simultaneously, was compared with group drug counseling, which focuses on
      substance use. The authors hypothesized that patients receiving integrated group
      therapy would have fewer days of substance use and fewer weeks ill with bipolar
      disorder. METHOD: A randomized controlled trial compared 20 weeks of integrated
      group therapy or group drug counseling with 3 months of posttreatment follow-up.
      Sixty-two patients with bipolar disorder and current substance dependence,
      treated with mood stabilizers for >or=2 weeks, were randomly assigned to
      integrated group therapy (N=31) or group drug counseling (N=31). The primary
      outcome measure was the number of days of substance use. The primary mood outcome
      was the number of weeks ill with a mood episode. RESULTS: Intention-to-treat
      analysis revealed significantly fewer days of substance use for integrated group
      therapy patients during treatment and follow-up. Groups were similar in the
      number of weeks ill with bipolar disorder during treatment and follow-up,
      although integrated group therapy patients had more depressive and manic
      symptoms. CONCLUSIONS: Integrated group therapy, a new treatment developed
      specifically for patients with bipolar disorder and substance dependence, appears
      to be a promising approach to reduce substance use in this population.

PMID- 17202552
TI  - Diagnostic reliability of telepsychiatry in American Indian veterans.
AB  - OBJECTIVE: This study examined the reliability of the Structured Clinical
      Interview for DSM-III-R (SCID) in the administration of psychiatric assessments
      by real-time videoconferencing compared to face-to-face assessment within a rural
      American Indian community. METHOD: The SCID was administered to 53 male American
      Indian veterans who were randomly assigned over two separate occasions by
      different interviewers to face-to-face and real-time interactive
      videoconferencing within 2 weeks. Comparisons were made with prevalences, the
      McNemar test, and the kappa statistic. RESULTS: With the exception of past-year
      substance dependence and abuse/dependence combined, there were no significant
      differences between face-to-face and videoconference administration. The majority
      of kappas calculated (76%) indicated a good or fair level of agreement.
      Externalizing disorders tended to elicit greater concordance than internalizing
      disorders. CONCLUSIONS: Overall, SCID assessment by live interactive
      videoconferencing did not differ significantly from face-to-face assessment in
      this population. Videoconferencing is a viable vehicle for clinical and research
      purposes.

PMID- 17202551
TI  - Perceived coercion and change in perceived need for admission in patients
      hospitalized for eating disorders.
AB  - OBJECTIVE: Ambivalence toward treatment is characteristic of eating disorders,
      and patients are often admitted to inpatient programs under pressure from
      clinicians, family, friends, educators, or employers. This study evaluated
      patient perceptions of the admissions process and perceived need for
      hospitalization and assessed whether these perceptions remain stable in the short
      term. METHOD: A total of 139 patients with eating disorders completed a 13-item
      self-report scale on the admission experience when they were admitted to a
      behavioral inpatient specialty program and again 2 weeks into their
      hospitalization. RESULTS: Patients with anorexia nervosa reported higher levels
      of perceived coercion and pressure and a lower sense of procedural justice than
      did those with bulimia. Patients under 18 (N=35) reported more perceived coercion
      than did adult patients (N=104), and a trend was noted for them to disagree that
      they needed hospitalization. Perceptions of coercion, of pressure by others
      toward hospitalization, and of procedural justice were stable in the short term.
      However, of the 46 patients (30 of them adults) who initially did not endorse
      needing admission, 20 patients (17 of them adults) changed their minds by 2 weeks
      into hospitalization and agreed that they needed hospital admission. CONCLUSIONS:
      Nearly half of patients with eating disorders who denied a need for treatment on
      admission converted to acknowledging that they needed to be admitted within 2
      weeks of hospitalization. Since treatment avoidance is associated with poor
      outcome, these findings suggest a need for studies assessing the long-term
      outcome and ethics of pressuring patients with eating disorders into treatment.

PMID- 17202553
TI  - Childhood antecedents of exposure to traumatic events and posttraumatic stress
      disorder.
AB  - OBJECTIVE: The authors prospectively examined childhood antecedents of exposure
      to traumatic events to estimate the risk of posttraumatic stress disorder (PTSD)
      among those exposed to trauma. METHOD: Two consecutive cohorts of children
      entering first grade of a public school system in a large mid-Atlantic city in
      the mid-1980s were followed into young adulthood (mean age=21). Exposure to
      traumatic events and PTSD were assessed in 75% of the original cohort (N=1,698).
      Childhood assessments, conducted upon entry into the first grade, included
      standardized measures of reading readiness, teacher ratings of behavioral
      problems, and child self-reports about depression and anxiety. Family
      characteristics were assessed by parental report. RESULTS: Young adults who had
      been rated by their first grade teacher as having aggressive/disruptive behavior
      problems were more likely to experience traumatic assaultive violence events
      (e.g., being mugged/threatened with a weapon, badly beaten-up) (relative
      risk=2.6) but not PTSD following trauma exposure. Youths with high levels of self
      rated depressive and anxious feelings in first grade were more likely to
      experience PTSD once exposed to trauma (relative risk=1.5). Youths who scored in
      the highest quartile on a reading test in the first grade were at lower risk for
      exposure to assaultive violence traumas. CONCLUSIONS: Childhood behavioral and
      depressive/anxious problems may influence the risk for PTSD directly by
      increasing the vulnerability to the PTSD effects of trauma exposure, and
      indirectly by increasing the likelihood of exposure to assaultive violence.

PMID- 17202554
TI  - Forty-year psychiatric outcomes following assessment for internalizing disorder
      in adolescence.
AB  - OBJECTIVE: The aim of this study was to define the long-term psychiatric outcomes
      of adolescent internalizing disorder in the general population, using data
      collected over 40 years from a national birth cohort. METHOD: A total of 3,279
      members of the Medical Research Council National Survey of Health and Development
      (the 1946 British birth cohort) underwent assessments of psychiatric symptoms,
      primarily anxiety and depression, at ages 13 and 15. Adolescents who had
      internalizing disorder at both ages 13 and 15 and those who had internalizing
      disorder at one of the two ages were compared with mentally healthy adolescents
      on various psychiatric outcomes in adulthood (ages 26-53), including the
      prevalence of mental disorders, self-reported trouble with "nerves," suicidal
      ideation, and treatment for psychiatric disorders. RESULTS: About 70% of
      adolescents who had internalizing disorder at both ages 13 and 15 had mental
      disorder at age 36, 43, or 53, compared with about 25% of the mentally healthy
      adolescents. They were also more likely than healthy adolescents to have self
      reported "nervous trouble" and to have been treated for psychiatric disorder
      during adulthood. None of these effects was apparent among subjects who had
      internalizing disorder at only one of the two adolescent assessments.
      CONCLUSIONS: The long-term psychiatric outcome for adolescents with persistent or
      recurrent internalizing disorder was poor, whereas the outcome for those who had
      a single episode was better than expected. The association between adolescent
      internalizing disorder and poor psychiatric outcomes in adulthood may be mediated
      by persistence or severity of symptoms in adolescence.

PMID- 17202555
TI  - Sex differences in clinical predictors of suicidal acts after major depression: a
      prospective study.
AB  - OBJECTIVE: Whether sex differences exist in clinical risk factors associated with
      suicidal behavior is unknown. The authors postulated that among men with a major
      depressive episode, aggression, hostility, and history of substance misuse
      increase risk for future suicidal behavior, while depressive symptoms, childhood
      history of abuse, fewer reasons for living, and borderline personality disorder
      do so in depressed women. METHOD: Patients with DSM-III-R major depression or
      bipolar disorder seeking treatment for a major depressive episode (N=314) were
      followed for 2 years. Putative predictors were tested with Cox proportional
      hazards regression analysis. RESULTS: During follow-up, 16.6% of the patients
      attempted or committed suicide. Family history of suicidal acts, past drug use,
      cigarette smoking, borderline personality disorder, and early parental separation
      each more than tripled the risk of future suicidal acts in men. For women, the
      risk for future suicidal acts was sixfold greater for prior suicide attempters;
      each past attempt increased future risk threefold. Suicidal ideation, lethality
      of past attempts, hostility, subjective depressive symptoms, fewer reasons for
      living, comorbid borderline personality disorder, and cigarette smoking also
      increased the risk of future suicidal acts for women. CONCLUSIONS: These findings
      suggest that the importance of risk factors for suicidal acts differs in
      depressed men and women. This knowledge may improve suicide risk evaluation and
      guide future research on suicide assessment and prevention.

PMID- 17202556
TI  - Gender-specific effects of the catechol-O-methyltransferase Val108/158Met
      polymorphism on cognitive function in children.
AB  - OBJECTIVE: The study aimed to determine the cognitive effect of the Val108/158Met
      polymorphism in the catechol-O-methyltransferase (COMT) gene in children before
      and during puberty. This polymorphism affects cognitive function in healthy
      adults and may contribute to risk for schizophrenia. METHOD: COMT genotype was
      determined for 8,707 children from the Avon Longitudinal Study of Parents and
      Children (ALSPAC), a geographically defined general population cohort of children
      born between April 1, 1991, and Dec. 31, 1992, in the southwest of England.
      Fourteen measures of cognitive function--including working memory, verbal and
      motor inhibition, attentional control, and IQ--were assessed at ages 8 and 10
      years. Any pubertal development at age 9 years was reported by parents. Effects
      of COMT genotype on cognition and interactions with gender and puberty were
      assessed using general linear models. RESULTS: In boys, genotype significantly
      affected executive function and explained up to 10 points normal variation in
      verbal IQ. The effects on IQ were significantly greater in pubertal than in
      prepubertal boys. In girls, there were no significant effects of genotype on
      cognition. CONCLUSIONS: This common polymorphism may be one of the genes of small
      effect that contribute to normal variation in IQ. The gender-specific nature of
      the effect and its possible interaction with puberty may be relevant to both
      normal cognitive and brain development and to abnormal development in disorders
      such as schizophrenia.

PMID- 17202557
TI  - Association of posttraumatic stress disorder with somatic symptoms, health care
      visits, and absenteeism among Iraq war veterans.
AB  - OBJECTIVE: Studies of soldiers from prior wars conducted many years after combat
      have shown associations between combat-related posttraumatic stress disorder
      (PTSD) and physical health problems. The current Iraq war has posed a
      considerable PTSD risk, but the association with physical health has not been
      well studied. METHOD: The authors studied 2,863 soldiers using standardized self
      administered screening instruments 1 year after their return from combat duty in
      Iraq. RESULTS: Among all participants, 16.6% met screening criteria for PTSD.
      PTSD was significantly associated with lower ratings of general health, more sick
      call visits, more missed workdays, more physical symptoms, and high somatic
      symptom severity. These results remained significant after control for being
      wounded or injured. CONCLUSIONS: The high prevalence of PTSD and its strong
      association with physical health problems among Iraq war veterans have important
      implications for delivery of medical services. The medical burden of PTSD
      includes physical health problems; combat veterans with serious somatic concerns
      should be evaluated for PTSD.

PMID- 17202558
TI  - Swept away: use of general medical and mental health services among veterans
      displaced by Hurricane Katrina.
AB  - OBJECTIVE: This study examined national patterns of outpatient service use by
      veterans from regions affected by Hurricane Katrina. METHODS: Analyses tracked
      use of general medical and mental/substance use services in September and October
      through December 2005 in New Orleans and Biloxi-Gulfport compared to a cohort
      receiving care during the same months in the previous 2 years. RESULTS: In
      adjusted models, veterans from New Orleans and Biloxi-Gulfport were,
      respectively, 73% and 41% less likely in September 2005 to use any outpatient
      services as were cohorts from 2003-2004. Particularly in New Orleans, the
      relative decline in service use was substantially greater for specialty mental
      health and substance use services than for general medical services. CONCLUSIONS:
      Although many veterans were able to obtain care after Hurricane Katrina, there
      was a substantial disruption in delivery of Veterans Administration services,
      with disproportionate declines in mental health and substance use care.

PMID- 17202559
TI  - Stimulant-induced enhanced sexual desire as a potential contributing factor in
      HIV transmission.
AB  - OBJECTIVE: Stimulant abuse is associated with an increased risk of contracting
      human immunodeficiency virus (HIV). Although sharing of contaminated needles is
      one of the routes by which HIV is spread, noninjection abusers are also at high
      risk. The authors investigated the effect of the stimulant drug methylphenidate
      (given intravenously) on sexual desire as a possible contributing factor to risky
      sexual behavior associated with the contraction of HIV. METHOD: The effects of
      intravenous methylphenidate (0.5 mg/kg) on self-reports of sexual desire (rated
      from 0-10) were evaluated in 39 comparison subjects and 39 cocaine abusers.
      RESULTS: Intravenous methylphenidate significantly increased self-reports of
      sexual desire in comparison subjects (1.4 versus 3.7) and cocaine abusers (2.8
      versus 4.8). CONCLUSIONS: Stimulant-induced enhancement of sexual desire could be
      one mechanism by which stimulant drugs such as cocaine and methamphetamine
      increase the risk for HIV transmission even when they are not injected.

PMID- 17202560
TI  - A comparison of aripiprazole, methylphenidate, and placebo for amphetamine
      dependence.
AB  - OBJECTIVE: Problems related to illegal amphetamine use have become a major public
      health issue in many developed countries. To date, evidence on the effectiveness
      of psychosocial treatments has remained modest, and no pharmacotherapy has proven
      effective for amphetamine dependence. METHOD: Individuals meeting DSM-IV criteria
      for intravenous amphetamine dependence (N=53) were randomly assigned to receive
      aripiprazole (15 mg/day), slow-release methylphenidate (54 mg/day), or placebo
      for 20 weeks. The study was terminated prematurely due to unexpected results of
      interim analysis. An intention-to-treat analysis was used. The primary outcome
      measure was the proportion of amphetamine-positive urine samples. RESULTS:
      Patients allocated to aripiprazole had significantly more amphetamine-positive
      urine samples than patients in the placebo group (odds ratio=3.77, 95% CI=1.55
      9.18), whereas patients who received methylphenidate had significantly fewer
      amphetamine-positive urine samples than patients who had received placebo (odds
      ratio=0.46, 95% CI=0.26-0.81). CONCLUSIONS: Methylphenidate is an effective
      treatment for reducing intravenous drug use in patients with severe amphetamine
      dependence.

PMID- 17202561
TI  - Effects of parental PTSD on the cortisol response to dexamethasone administration
      in their adult offspring.
AB  - OBJECTIVE: The authors used a low-dose dexamethasone suppression test to examine
      the effect of a PTSD risk factor, parental PTSD, on cortisol negative feedback
      inhibition in adult offspring of Holocaust survivors with PTSD (N=13) versus
      without PTSD (N=12) as well as a comparison group of offspring whose parents had
      no Holocaust exposure (N=16). METHOD: Blood samples were obtained at 8:00 a.m.
      for the determination of baseline cortisol. Participants ingested 0.5 mg of
      dexamethasone at 11:00 p.m., and blood samples were obtained again at 8:00 a.m.
      the following day. RESULTS: Enhanced cortisol suppression in response to
      dexamethasone was associated primarily with parental PTSD status, with minimal
      contribution of subjects' own trauma-related symptoms. CONCLUSIONS: Enhanced
      cortisol negative feedback inhibition may be associated with PTSD because it is
      related to the PTSD risk factor of parental PTSD.

PMID- 17202562
TI  - Trauma and psychosis: an analysis of the National Comorbidity Survey.
AB  - OBJECTIVE: The authors hypothesized that the likelihood of psychosis
      classification would increase with traumatic experiences. METHOD: Data from the
      National Comorbidity Survey were used to estimate the relationship between
      interpersonal trauma and the likelihood of a classification of psychosis.
      RESULTS: Childhood physical abuse predicted psychosis, and there was a
      significant cumulative relationship between trauma and psychosis, with number of
      trauma types experienced increasing the probability of psychosis. CONCLUSIONS:
      Overall, physical abuse predicted psychosis. In addition, a significant gender-by
      rape interaction was observed, with rape having higher predictive value for
      psychosis in male subjects.

PMID- 17202563
TI  - Violence and mandated treatment: future considerations.

PMID- 17202564
TI  - Comment on "tardive dyskinesia circa 2006".

PMID- 17202565
TI  - Manic episode during treatment with aripiprazole.

PMID- 17202566
TI  - Quetiapine cross reactivity with urine methadone immunoassays.

PMID- 17202567
TI  - Intravenous quetiapine-cocaine use ("Q-ball").

PMID- 17202569
TI  - Quetiapine addiction?

PMID- 17202568
TI  - Hyperglycemia in a 7-year-old child treated with aripiprazole.

PMID- 17202571
TI  - Safety of aripiprazole: high serum levels in a CYP2D6 mutated patient.

PMID- 17202573
TI  - Risk factors and consequences of unwanted sex among university students: hooking
      up, alcohol, and stress response.
AB  - This is the first study of unwanted sexual experiences in the collegiate "hooking
      up" culture. In a representative sample of 178 students at a small liberal arts
      university. Twenty-three percent of women and 7% of men surveyed reported one or
      more experiences of unwanted sexual intercourse. Seventy-eight percent of
      unwanted vaginal, anal, and oral incidents took place while--"hooking up,"-
      whereas 78% of unwanted fondling incidents occurred at parties or bars. The most
      frequently endorsed reason for unwanted sexual intercourse was impaired judgment
      due to alcohol. The most frequently endorsed reason for unwanted fondling was
      that it happened before the perpetrator could be stopped. Of those affected by
      unwanted sexual intercourse or unwanted fondling, 46.7% and 19.2% reported
      unwanted memories, 50% and 32.7% reported avoidance and numbing responses, and
      30% and 26.9% reported hyperarousal responses, respectively. A preliminary model
      of unwanted sex and collegiate social dynamics is proposed to provide a heuristic
      for further research.

PMID- 17202574
TI  - Punking and bullying: strategies in middle school, high school, and beyond.
AB  - Punking is a practice of verbal and physical violence, humiliation, and shaming
      usually done in public by males to other males. This definition is based on
      interviews and discussion groups with 32 adolescent boys and on media sources
      within which adolescent males are embedded. Discourse analysis findings reveal
      that punking terminology and behaviors are usually interchangeable with bullying
      terminology and behaviors. Both practices are purposeful strategies taken up and
      used by many boys to affirm masculinity norms of toughness, strength, dominance,
      and control. Implications from this research promote a shift in understandings of
      how masculinity norms are achieved. Further, the research suggests that by
      bringing critical attention to social accountability for production of unhealthy
      norms and the violent practices that affirm these norms, we might well extend the
      scope and focus of intervention into harmful practices of violence, such as
      punking and bullying.

PMID- 17202575
TI  - Mental health, quality of life, and health functioning in women veterans:
      differential outcomes associated with military and civilian sexual assault.
AB  - The present study examined psychiatric, physical, and quality-of-life functioning
      in a sample of 270 women veterans receiving outpatient treatment at a Veterans
      Affairs medical center. Participants were interviewed regarding their civilian
      (CSA) and military sexual assault (MSA) histories, and data regarding quality of
      life and health outcomes were obtained through structured interviews and
      questionnaires. Women veterans with CSA histories reported significantly poorer
      physical, psychiatric, and quality-of-life functioning compared to those without
      a history of sexual assault. Furthermore, women veterans with an MSA history
      demonstrated additional negative consequences above and beyond the effects of
      CSA. The study sample was comparable to a national random sample of women
      veterans who access care in the Veterans Affairs healthcare system, increasing
      the generalizibility of the results.

PMID- 17202576
TI  - Perceptions of victimization risk and fear of crime among lesbians and gay men.
AB  - Research on fear of crime has evolved to suggest the existence of a complex
      relationship between individual, lifestyle, and contextual factors. Past work
      generally focuses on predominantly heterosexual populations; this study examines
      correlates of fear of crime and perceptions of risk among a sample of 272 self
      identified lesbians and gay men. Higher levels of perceived risk and fear of
      victimization were found among females, persons in neighborhoods characterized by
      incivility, and persons who had experienced previous victimization. Perceived
      risks of personal and property victimization were similar for males and females.
      Contrary to past research, women did not seem to view all types of potential
      victimization as opportunities for sexual assault. Instead, fear of victimization
      was offense specific--past personal victimization predicted fear of future
      personal victimization, and past property victimization predicted fear of future
      property victimization. Similarities and differences between current findings and
      suggestions for future research are discussed.

PMID- 17202577
TI  - Understanding the factors that affect the severity of juvenile stranger sex
      offenses: the effect of victim characteristics and number of suspects.
AB  - Understanding factors that affect the severity of a juvenile-stranger sexual
      assault has implications for crime prevention, and potentially, the assessment
      and treatment of juvenile sex offenders. This study investigated how victim
      characteristics and the number of suspects affected the use of physical violence
      and weapons and the occurrence of penetration in 495 allegations of sexual
      assault committed by juveniles against strangers. Statistically significant
      interactions between victim age and gender were found for occurrence of
      penetration and use of violence. Differences in offense characteristics were also
      found between offenses with varying victim-suspect age differences. When
      comparing the rate of penetration in the presence and absence of violence, little
      change was observed for lone suspects. However, the rate of penetration increased
      significantly for groups in the presence of physical violence, suggesting that
      violence in this context may be more expressive than instrumental. Theoretical
      explanations and practical implications are considered.

PMID- 17202578
TI  - Using indirect questions to detect intimate partner violence: the SAFE-T
      questionnaire.
AB  - A screening instrument for detecting intimate partner violence (IPV) was
      developed using indirect questions. The authors identified 5 of 18 items studied
      that clearly distinguished victims of IPV from a random group of health
      conference attendees with a sensitivity of 85% and a specificity of 87%. This 5
      item instrument (SAFE-T) was then tested on 435 women presenting to three
      emergency departments and the results compared to a direct question regarding
      current abuse. The SAFE-T questions detected only 54% of the women who admitted
      being abused and correctly classified 81% of the women who said they were not
      victims. The 1-year prevalence of IPV in this sample of women presenting to an
      emergency department was 11.6%. The authors conclude that indirect questioning of
      women appears to be more effective at ruling out IPV in an emergency department
      population and may be less useful for women "early" in an abusive relationship.

PMID- 17202579
TI  - Current psychopathology in previously assaulted older adults.
AB  - Older adult women age 55+ years (N = 549) were interviewed as part of a
      population-based epidemiological research study of lifetime experiences with
      physical and sexual assault and current mental health problems. Although overall
      rates of psychopathology were low, producing very small cells for comparison,
      women who reported experiencing physical assault an average of 28 years
      previously were more likely to present with past year substance abuse,
      depression, and avoidance and reexperiencing symptoms of posttraumatic stress
      disorder (PTSD) than those with no previous physical or sexual assault. Women who
      reported experiencing sexual assault an average of 50 years previously were more
      likely to present with autonomic arousal and avoidance symptoms of PTSD than
      those with no prior sexual assault. The aforementioned findings should be
      considered with caution, however, as sample cell sizes were minimal for all but
      the PTSD symptom subtypes. Mental health service implications for older adults
      are discussed.

PMID- 17202580
TI  - Can microparticles contribute to inflammatory bowel disease: innocuous or
      inflammatory?

PMID- 17202582
TI  - Making sense of it: roles of the sensory circumventricular organs in feeding and
      regulation of energy homeostasis.
AB  - Obesity is associated with significant health risks including stroke and heart
      disease. The prevalence of obesity has dramatically increased over the past 20
      years. Although the development of obesity is clearly related to changing
      lifestyles, the central nervous system plays a key role in regulation of energy
      balance. To develop effective strategies for treating obesity, we must gain a
      clearer understanding of the neuro-circuitry and signaling mechanisms involved.
      Toward this end, recent progress has been made in the understanding of the roles
      played by the sensory circumventricular organs (CVOs) of the brain. These areas
      lack the normal blood-brain barrier and thus act as transducers of signals
      between the blood, other centers in the brain, and the cerebrospinal fluid. This
      review focuses on the roles played by the sensory CVOs in detecting and
      responding to a number of signals that carry information regarding nutritional
      status, including cholecystokinin, amylin, ghrelin, peptide YY, pancreatic
      polypeptide, leptin, adiponectin, and glucose.

PMID- 17202581
TI  - Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals.
AB  - Metabolic conversion of inorganic arsenic into methylated products is a multistep
      process that yields mono-, di-, and trimethylated arsenicals. In recent years, it
      has become apparent that formation of methylated metabolites of inorganic arsenic
      is not necessarily a detoxification process. Intermediates and products formed in
      this pathway may be more reactive and toxic than inorganic arsenic. Like all
      metabolic pathways, understanding the pathway for arsenic methylation involves
      identification of each individual step in the process and the characterization of
      the molecules which participate in each step. Among several arsenic
      methyltransferases that have been identified, arsenic (+3 oxidation state)
      methyltransferase is the one best characterized at the genetic and functional
      levels. This review focuses on phylogenetic relationships in the deuterostomal
      lineage for this enzyme and on the relation between genotype for arsenic (+3
      oxidation state) methyltransferase and phenotype for conversion of inorganic
      arsenic to methylated metabolites. Two conceptual models for function of arsenic
      (+3 oxidation state) methyltransferase which posit different roles for cellular
      reductants in the conversion of inorganic arsenic to methylated metabolites are
      compared. Although each model accurately represents some aspects of enzyme's role
      in the pathway for arsenic methylation, neither model is a fully satisfactory
      representation of all the steps in this metabolic pathway. Additional information
      on the structure and function of the enzyme will be needed to develop a more
      comprehensive model for this pathway.

PMID- 17202583
TI  - A comparison of arteries and veins in oxidative stress: producers, destroyers,
      function, and disease.
AB  - Reactive oxygen species (ROS) are by-products of oxygen metabolism, normally
      present in low levels inside cells, where they participate in signaling
      processes. The delicate balance in the continuous cycle of ROS generation and
      inactivation is maintained by enzymatic and nonenzymatic endogenous systems.
      Overwhelming production of ROS (by such sources as the mitochondrial electron
      transport chain, NADPH oxidase, xanthine oxidase, or uncoupled nitric oxide
      synthase), when inadequately counteracted by destruction through antioxidant
      systems (such as superoxide dismutase or catalase), leads to a prooxidant state
      also known as oxidative stress. Increased levels of ROS and markers of oxidative
      stress have been consistently found in such cardiovascular diseases as
      atherosclerosis or hypertension, although controversy still exists over the
      pathophysiological role of oxidative stress in these conditions. ROS can modulate
      vascular function either by direct oxidative damage or by activating cellular
      signaling pathways that lead to abnormal contractile, inflammatory,
      proliferative, or remodeling properties of the blood vessel. Most current
      research focuses on these processes in arteries, leaving veins, "the other side"
      of vascular biology, in obscurity. Veins are different structurally and
      functionally from arteries. Equipped with a smaller smooth muscle layer compared
      to arteries, but being able to accommodate 70% of the circulating blood volume,
      veins can modulate cardiovascular homeostasis and contribute significantly to
      hypertension pathogenesis. Although the reports on the quantitative differences
      in ROS production in veins compared to arteries had conflicting results, there is
      a clear qualitative difference in ROS metabolism and utilization between the two
      vessel types. This review will compare and contrast the current knowledge of ROS
      metabolism in arteries versus veins in both physiological and pathophysiological
      conditions. Our understanding of the mechanisms underlying vascular diseases
      would greatly benefit from a more thorough exploration of the role of veins and
      venous oxidative stress.

PMID- 17202584
TI  - Cyclic nucleotide phosphodiesterase (PDE) inhibitors: novel therapeutic agents
      for progressive renal disease.
AB  - Cyclic nucleotides are recognized as critical mediators of many renal functions,
      including solute transport, regulation of vascular tone, proliferation of
      parenchymal cells, and inflammation. Although most studies have linked elevated
      cAMP levels to activation of protein kinase A, cAMP can also directly activate
      cyclic nucleotide gated ion channels and can signal through activation of GTP
      exchange factors. Cyclic AMP signaling is highly compartmentalized through plasma
      membrane localization of adenylyl cyclase and expression of scaffolding proteins
      that anchor protein kinase A to specific intracellular locations. Cyclic
      nucleotide levels are largely regulated through catabolic processes directed by
      phosphodiesterases (PDEs). The PDE superfamily is large and complex, with over 60
      distinct isoforms that preferentially hydrolyze cAMP, cGMP, or both. PDEs
      contribute to compartmentalized cyclic nucleotide signaling. The unique cell- and
      tissue-specific distribution of PDEs has prompted the development of highly
      specific PDE inhibitors to treat a variety of inflammatory conditions. In
      experimental systems, PDE inhibitors have been employed to demonstrate functional
      compartmentalization of cyclic nucleotide signaling in the kidney. For example,
      mitogenesis in glomerular mesangial cells and normal tubular epithelial cells is
      negatively regulated by an intracellular pool of cAMP that is metabolized by
      PDE3, but not by other PDEs. In Madin-Darby canine kidney cells, an in vitro
      model of polycystic kidney disease, an intracellular pool of cAMP directed by
      PDE3 stimulates mitogenesis. In mesangial cells, an intracellular pool of cAMP
      directed by PDE4 inhibits reactive oxygen species and expression of the potent
      proin-flammatory cytokine monocyte chemoattractant protein 1. An intracellular
      pool of cGMP directed by PDE5 regulates solute transport. PDE5 inhibitors
      ameliorate renal injury in a chronic renal disease model. In this overview, we
      highlight recent studies to define relationships between PDE expression and renal
      function and to provide evidence that PDE inhibitors may be effective agents in
      treating chronic renal disease.

PMID- 17202585
TI  - Cordyceps sinensis mycelium extract induces human premyelocytic leukemia cell
      apoptosis through mitochondrion pathway.
AB  - This study was to identify the signaling pathways for the induction of HL-60 cell
      apoptosis by Cordyceps sinensis mycelium extract (CSME). CSME at 25 mug/ml
      induced nuclear fragmentation and DNA degradation, two hallmark events of
      apoptosis, in the HL-60 cells within 12-24 hrs of treatment. Concomitantly,
      several major events in the mitochondrial signal pathway occurred, including the
      loss of MTP (DeltaPsi(m)), cytochrome c release into the cytoplasm, the decrease
      in Bcl-2 protein level, the translocation of Bax protein from cytoplasm into
      mitochondria, and the activation of caspase-2, -3, and -9, but caspase-8, the
      initiator caspase in the death receptor pathway, was not activated. These results
      suggest that CSME induces apoptosis in HL-60 cell through the mitochondrial
      pathway rather than the death receptor pathway.

PMID- 17202586
TI  - Lipid metabolism in the adipose tissues of a carnivore, the raccoon dog, during
      prolonged fasting.
AB  - Previous studies on laboratory rodents, rabbits, and humans have demonstrated
      that adipose tissue fatty acid (FA) mobilization is selective, and its efficiency
      is related to the molecular structure of FAs. This study was undertaken to find
      out whether such preferences of FA mobilization are a general feature of
      mammalian white adipose tissue (WAT) and are also manifested in carnivores.
      Fractional mobilization of a wide spectrum of FAs was studied by gas-liquid
      chromatography from six subcutaneous (scapular, rump, ventral) and intra
      abdominal (omental, mesenteric, retroperitoneal) WAT depots of raccoon dogs
      (Nyctereutes procyonoides) fed or fasted for 2 months. Fasting stimulated the
      mobilization of shorter-chain saturated, mono-unsaturated (MUFAs), and
      polyunsaturated FAs (PUFAs). The effects of unsaturation and the position of the
      first double bond from the methyl end were more inconsistent. The effect of
      double-bond position may be due to chain shortening of longer-chain MUFAs and
      preferential utilization of n-3 PUFAs over n-6 PUFAs. Moreover, there were site
      specific differences in fractional mobilization, the omental adipose tissue being
      the most divergent. The in vivo FA mobilization from the regional WAT depots of a
      carnivore was selective, and the molecular structure of the FA affected its
      efficiency.

PMID- 17202587
TI  - Prevention of mammary tumorigenesis by intermittent caloric restriction: does
      caloric intake during refeeding modulate the response?
AB  - Chronic caloric restriction (CCR) prevents mammary tumorigenesis in rodents, but
      a protective effect for intermittent caloric restriction (ICR) is less well
      documented. We recently reported that ICR reduced mammary tumor (MT) incidence of
      mouse mammary tumor virus-transforming growth factor (MMTV-TGF)-alpha mice to a
      greater extent than did CCR. Here, we repeated this protocol and obtained serum
      and tissue samples. Ad libitum (AL) MMTV-TGF-alpha mice were fed AIN-93M diet.
      Beginning at 10 weeks of age, ICR mice received isocaloric AIN-93M-mod diet (2
      fold increases in protein, fat, vitamins, and minerals) at 50% of ad libitum for
      3 weeks followed by 3 weeks refeeding with AIN-93M diet. CCR mice were pair-fed
      AIN-93M:AIN-93M-mod (2:1) matching intakes for restriction/refeeding cycles. Mice
      were sacrificed for MT size, at 79 (end of 12th restriction) or at 80 (1 week
      after 12th refeeding) weeks of age. AL and ICR-80 mice had heavier body weights
      than ICR-79 and CCR mice (P < 0.0001). Cumulative food intakes of ICR and CCR
      mice were reduced 12% and 15% versus AL mice (P < 0.0001). However, ICR mice
      consumed significantly (P < 0.0001) more food than did AL mice during refeeding.
      MT incidence was 84%, 13%, and 27% for AL, ICR, and CCR mice, respectively. MT
      weight (P < 0.0011) and number (P < 0.01) were higher for AL mice compared with
      ICR and CCR mice. AL and ICR-80 mice had similar serum IGF-I levels, but only AL
      values were higher than those of ICR-79 and CCR mice (P < 0.0017). ICR mice had
      more MT DNA breaks compared with AL and CCR mice, suggesting enhanced apoptosis
      (P < 0.02). AL mice had higher mammary fat pad ObR and ObRb leptin receptor mRNA
      expression than did ICR and CCR mice (P < 0.001), but there was no effect on MTs.
      These results confirm that ICR prevents development of MTs to a greater extent
      than does CCR, although "overeating" during refeeding may compromise this
      protection.

PMID- 17202588
TI  - Homocysteine thiolactone-induced hyperhomocysteinemia does not alter
      concentrations of cholesterol and SREBP-2 target gene mRNAS in rats.
AB  - The present rat study was conducted to test whether hyper-homocysteinemia induced
      by dietary homocysteine (Hcy) alters the cholesterol concentration in plasma and
      tissue and the gene expression of genes involved in cholesterol biosynthesis and
      uptake. Therefore, rats were fed 100 or 200 mg Hcy per kilogram body mass per day
      (Hcy100 group and Hcy200 group, respectively) as dl-homocysteine thiolactone, or
      an Hcy-free diet, which served as control, over 14 days. Rats from the Hcy100
      group and the Hcy200 group had higher plasma Hcy concentrations (34.4 +/- 4.6 and
      69.4 +/- 11.5 microM, respectively) than rats fed an Hcy-free diet (9.5 +/- 1.7
      microM). The concentration of Hcy in liver was 2.6 and 3.8 times higher, and in
      small intestine was 2.6 and 5.1 times higher, in the Hcy100 group and the Hcy200
      group, respectively, than in control rats (P < 0.05). The concentrations of
      cholesterol in plasma, lipoproteins, liver, and small intestine and the relative
      mRNA concentrations of sterol regulatory element-binding protein 2 (SREBP-2), 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and low-density
      lipoprotein (LDL) receptor in liver and small intestine were not influenced by dl
      homocysteine thiolactone supplementation. In conclusion, in view of the
      experimental conditions used here, increased plasma and tissue concentrations of
      Hcy do not alter cholesterol metabolism of liver and intestine.

PMID- 17202589
TI  - Functional alterations in macrophages after hypoxia selection.
AB  - Regions of low oxygen tension are common features of inflamed and infected
      tissues and provide physiologic selective pressure for the expansion of cells
      with enhanced hypoxia tolerance. The aim of this study was to investigate whether
      macrophages resistant to death induced by hypoxia were accompanied by functional
      alterations. A mouse macrophage cell line (J774 cells) was used to obtain
      subpopulations of death-resistant macrophages induced by long-term exposure to
      severe hypoxia (<1% O(2)). The results indicated that exposing J774 macrophages
      to periods of severe hypoxia results in the selection of cells with phenotypes
      associated with the modulation of heat-shock protein 70 kDa (HSP70) expression,
      tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) production and
      reduced susceptibility to parasite Leishmania infection. Thus, we suggest that
      hypoxia-selected macrophages may influence the outcome of inflammation and
      infection.

PMID- 17202590
TI  - Chemotherapy-induced diarrhea is associated with changes in the luminal
      environment in the DA rat.
AB  - The microflora of the gastrointestinal tract (GIT) are a complex ecosystem,
      performing a number of beneficial functions. Irinotecan causes both early and
      late diarrhea, the latter possibly caused, in part, by changes in the microflora
      of the GIT. Female DA rats were given atropine subcutaneously, prior to a single
      200 mg/kg intraperitoneal dose of irinotecan. Animals were monitored for diarrhea
      and killed at 30 and 60 mins, 2, 6, 12, 24, 48, and 72 hrs after chemotherapy
      administration. Control rats received no treatment. Fecal samples and stomach,
      jejunum, and colon samples were collected and stored at -70 degrees C until
      required. Standard microbiological culture techniques were used to grow and
      isolate the flora. Biochemical tests were used to identify the bacteria. The
      level of growth was noted for relative comparison between time points and graded
      accordingly. Early diarrhea was observed in the rats from 2-6 hrs after
      treatment, after which time the diarrhea resolved. Late onset diarrhea was
      apparent 72 hrs after treatment. Changes were seen in the flora of the stomach,
      jejunum, colon and feces. The majority of microflora changes were seen 6, 12, and
      24 hrs after treatment, with a relative increase or decrease in the presence of
      bacteria in comparison with control rats. In some rats bacteria were not observed
      at all time points, and different bacteria not seen in control animals were
      identified in rats treated with irinotecan. These changes were observed up to 72
      hrs after treatment. In conclusion, irinotecan treatment causes changes in the
      flora of the stomach, jejunum, colon, and feces of rats and is associated with
      the development of diarrhea. These changes in flora may have systemic effects and
      in particular may contribute to the development of chemotherapy-induced
      mucositis.

PMID- 17202591
TI  - Fine particles that adsorb lipopolysaccharide via bridging calcium cations may
      mimic bacterial pathogenicity towards cells.
AB  - Fine particles (10(2)- to 10(3)-nm diameter) are potentially potent adjuvants in
      acquired immune responses but little is known about their interaction with
      pathogen-associated molecular patterns (PAMPs) and impact upon innate immunity.
      Here we show that 200-nm-sized, food-grade titanium dioxide avidly binds
      lipopolysaccharide (LPS) with bridging calcium cations, and the complex induces
      marked proinflammatory signalling in primary human mononuclear phagocytes. In
      particular, caspase 1-dependent interleukin-1beta (IL-1beta) secretion was
      induced at levels far greater than for the sum of the individual components, and
      without concomitant secretion of modulatory cytokines such as interleukin-1
      receptor antagonist or transforming growth factor-beta1 (TGF-beta1). Secondly,
      the conjugate induced apoptotic-like cell death. These responses were inhibited
      by blockade of both phagocytosis and scavenger receptor uptake. Specific caspase
      1-facilitated IL-1beta secretion and apoptosis following phagocytosis are
      features of cellular responses to certain invasive, enteric pathogens, and hence
      induction of these events may be mimicked by fine particle-LPS conjugates. The
      inadvertent adsorption of PAMPs to ingested, inhaled, or "wear" fine particulate
      matter provides a further potential mechanism for the proinflammatory nature of
      fine particles.

PMID- 17202592
TI  - Effect of the isoflavone genistein against galactose-induced cataracts in rats.
AB  - Worldwide, ocular cataracts are a major cause of human blindness. A key goal of
      cataract-related research is to identify simple, cost-efficient but effective
      ways to prevent cataract formation or progression. Genistein is a naturally
      occurring dietary isoflavone with well-documented estrogenic, antioxidant, and
      protein tyrosine kinase inhibitor activity, which in turn modulates the activity
      of several enzymes involved in cell signaling and proliferation. Furthermore,
      many isoflavones have been shown to be potent inhibitors of aldose reductase,
      which is an important rate-limiting enzyme in the process of cataract induction
      in the metabolic disease galactosemia. In order to assess the potential for
      genistein to mitigate cataract formation, we have studied its effects in the
      animal model of dietary galactose-induced cataracts in adult male rats. Our
      experimental hypothesis was that dietary genistein would prevent or delay the
      progression of cataracts induced by high dietary intake of galactose. Our results
      show that the isoflavone genistein was not able to completely prevent galactose
      induced cataract formation, but genistein did delay the progression of cataracts
      induced by dietary galactose. In addition, we found that dietary galactose
      decreased concentrations of serum somatostatin, while adding genistein decreased
      the serum glucose level but increased the serum testosterone level. As an initial
      inquiry into the mechanisms by which the partial protective effect of genistein
      could be mediated, we found that genistein increased the expression of connexin
      (Cx) 43 in the lens but did not affect the expression of soluble guanylyl cyclase
      (sGC) subunits. This finding suggests that the partial protective effect of
      genistein on cataract induction appears to be unrelated to sGC but may be
      mediated by enhanced expression of Cx43 and changed metabolic state.

PMID- 17202593
TI  - Saponins from Tribulus terrestris L are less toxic for normal human fibroblasts
      than for many cancer lines: influence on apoptosis and proliferation.
AB  - The objective of the study was to explore the influence of saponins derived from
      Tribulus terrestris L. (TT) on normal human skin fibroblasts and to compare it
      with their anticancer properties. In this study, [3H]thymidine incorporation and
      MTT to assess cell proliferation and viability, respectively, and immunoblotting
      and HPLC analysis to explore intracellular signal transduction pathways have been
      used. We found that TT caused a dose-dependent decrease in [3H]thymidine
      incorporation into the DNA of treated fibroblast compared to the untreated
      controls. Viability of treated cells remained within the control levels with
      treatment of up to 5 micro g TT/ml medium. It was significantly depressed with
      incubation in > or =6 micro g TT/ml medium with an IC50 of 12.6 micro g TT/ml of
      cultivating media. ERK1/2 was significantly dephosphorylated at 5 mins of
      incubation with TT until the 48th hour, when phosphorylation slightly recovered,
      but was still below the control levels. In contrast, p38 and JNK phosphorylation
      was positively influenced, with peaks at 1 hr and 24 hrs of incubation
      respectively. Phosphorylation/dephosphorylation events of SAPK/MAPK clearly
      correlated with Mkp-1 induction. Procaspase 3 was activated after 5 mins of
      incubation and coincided with a rapid actin cleavage. There was a significant
      decrease of putrescine concentration and a concomitant increase of spermidine and
      spermine at 2 mins of treatment. According to our results, TT is less toxic for
      normal human skin fibroblasts in comparison to many cancer lines investigated in
      previous studies. The molecular mechanism of this cytotoxicity involves up- and
      downregulation of polyamines' homeostasis, suppression of proliferation, and
      induction of apoptosis. Further research in this field using animal models would
      help to explore and interpret the potential properties of TT as an anticancer
      supplement.

PMID- 17202594
TI  - Inflammatory biomarker, neopterin, suppresses B lymphopoiesis for possible
      facilitation of granulocyte responses, which is severely altered in age-related
      stromal-cell-impaired mice, SCI/SAM.
AB  - Neopterin is produced by monocytes and is a useful biomarker of inflammatory
      activation. We found that neopterin enhanced in vivo and in vitro granulopoiesis
      triggered by the stromal-cell production of cytokines in mice. The effects of
      neopterin on B lymphopoiesis during the enhancement of granulopoiesis were
      determined using the mouse model of senescent stromal-cell impairment (SCI), a
      subline of senescence-accelerated mice (SAM). In non-SCI mice (a less senescent
      stage of SCI mice), treatment with neopterin decreased the number of colonies, on
      a semisolid medium, of colony-forming units of pre-B-cell progenitors (CFU-preB)
      from unfractionated bone marrow (BM) cells, but not that from a population rich
      in pro-B and pre-B cells without stromal cells. Neopterin upregulated the
      expression of genes for the negative regulators of B lymphopoiesis such as tumor
      necrosis factor-alpha (TNF-alpha ), interleukin-6 (IL-6), and transforming growth
      factor-beta (TGF-beta) in cultured stromal cells, implying that neopterin
      suppressed the CFU-preB colony formation by inducing negative regulators from
      stromal cells. The intraperitoneal injection of neopterin into non-SCI mice
      resulted in a marked decrease in the number of femoral CFU-preB within 1 day,
      along with increases in TNF-alpha and IL-6 expression levels. However, in SCI
      mice, in vivo and in vitro responses to B lymphopoiesis and the upregulation of
      cytokines after neopterin treatment were less marked than those in non-SCI mice.
      These results suggest that neopterin predominantly suppressed lymphopoiesis by
      inducing the production of negative regulators of B lymphopoiesis by stromal
      cells, resulting in the selective suppression of in vivo B lymphopoiesis. These
      results also suggest that neopterin facilitated granulopoiesis in BM by
      suppressing B lymphopoiesis, thereby contributing to the potentiation of the
      inflammatory process; interestingly, such neopterin function became impaired
      during senescence because of attenuated stromal-cell function, resulting in the
      downmodulation of the host-defense mechanism in the aged.

PMID- 17202595
TI  - Regulation of type II luteinizing hormone-releasing hormone (LHRH-II) gene
      expression by the processed peptide of LHRH-I, LHRH-(1-5) in endometrial cells.
AB  - Luteinizing hormone-releasing hormone (LHRH) was first isolated in the mammalian
      hypothalamus and shown to be the primary regulator of the reproductive system
      through its initiation of pituitary gonadotropin release. Since its discovery,
      this form of LHRH (LHRH-I) has been shown to be one of many structural variants
      with a variety of roles in both the brain and peripheral tissues. Enormous
      interest has been focused on LHRH-I, LHRH-II, and their cognate receptors as
      targets for designing therapies to treat cancers of the reproductive system. LHRH
      I is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves
      the hormone at the Tyr(5)-Gly(6) bond. We have previously reported that the
      autoregulation of LHRH gene expression can also be mediated by its processed
      peptide, LHRH-(1-5). Given its importance in the brain, we have investigated the
      role of the specific processed peptide of LHRH-I, LHRH-(1-5), within Ishikawa
      cells, a human endometrial cell line. Using real-time polymerase chain reaction,
      we observed that LHRH-(1-5) upregulates LHRH-II mRNA expression in Ishikawa cells
      but does not exert any influence on LHRH-I mRNA levels. This is in contrast to
      the effects of LHRH-I, which affects the expression of LHRH-I mRNA. Our findings
      support a potential role for LHRH-(1-5) as a processed metabolite in the
      endometrium. Further investigations are needed to determine the role of this
      processed metabolite and to identify specific pathways involved in LHRH-(1-5)
      signaling.

PMID- 17202597
TI  - Metabolism of stevioside by healthy subjects.
AB  - Stevioside (250-mg capsules) was given thrice daily for 3 days to 10 healthy
      subjects. Blood samples were collected and blood pressure measured after
      nocturnal fasting, before and at different time points during the third day of
      the administration of stevioside. No significant differences were found between
      the control and the stevioside condition for blood pressure and blood biochemical
      parameters. The 24-hr urinary volume and urinary excretion of electrolytes were
      not significantly different. Likewise, no significant difference was found for
      mean blood glucose and insulin between control and stevioside conditions. Thus,
      oral stevioside is not directly effective as a hypotensive or hypoglycemic agent
      in healthy subjects at the dose administered in this study. Stevioside, free
      steviol, and steviol metabolites were analyzed in blood, feces, and urine after 3
      days of stevioside administration. No uptake was found of stevioside by the
      gastrointestinal tract or the amounts taken up were very low and below the
      detection limit of the UV detector. Stomach juice did not degrade stevioside. All
      the stevioside reaching the colon was degraded by micro-organisms into steviol,
      the only metabolite found in feces. In blood plasma, no stevioside, no free
      steviol or other free steviol metabolites were found. However, steviol
      glucuronide (SV glu) was found in maximum concentrations of 33 micro g/ml (21.3
      micro g steviol equivalents/ml). In urine, no stevioside or free steviol were
      present, but SV glu was found in amounts of up to 318 mg/24-hr urine (205 mg
      steviol equivalents/24 hrs). No other steviol derivatives were detected. In
      feces, besides free steviol, no other steviol metabolites or conjugates were
      detected. Steviol was excreted as SV glu in urine.

PMID- 17202596
TI  - Signaling pathways implicated in hematopoietic progenitor cell proliferation and
      differentiation.
AB  - The objective of this study was to investigate the signal transduction pathways
      associated with the clonal development of myeloid and erythroid progenitor cells.
      The contribution of particular signaling molecules of protein tyrosine kinases
      (PTKs), mitogen-activated protein (MAP) kinase, and PI-3 kinase signaling to the
      growth of murine bone marrow colony forming unit-granulocyte-macrophage (CFU-GM)
      and erythroid (burst forming unit-erythroid [BFU-E] and colony forming unit
      erythroid [CFU-E]) progenitors was examined in studies performed in the presence
      or absence of specific signal transduction inhibitors. The results clearly
      pointed to different signal transducing intermediates that are involved in cell
      proliferation and differentiation depending on the cell lineage, as well as on
      the progenitors' maturity. Lineage-specific differences were obtained when
      chemical inhibitors specific for receptor- or nonreceptor-PTKs, as well as for
      the main groups of distinctly regulated MAPK cascades, were used because all of
      these compounds suppressed the growth of erythroid progenitors, with no major
      effects on myeloid progenitors. At the same time, differential involvement of
      MEK/extracellular signal-regulated kinase (ERK) MAPK transduction pathway was
      observed in the proliferation and/or differentiation of early, BFU-E, and late,
      CFU-E, erythroid progenitor cells. The results also demonstrated that
      phosphatydylinositol (PI)-3 kinase and nuclear factor kappaB (NF-kappaB)
      transcriptional factor were required for maintenance of both myeloid and
      erythroid progenitor cell function. Overall, the data obtained indicated that
      committed hematopoietic progenitors express a certain level of constitutive
      signaling activity that participates in the regulation of normal steady-state
      hematopoiesis and point to the importance of evaluating the impact of signal
      transduction inhibitors on normal bone marrow when used as potential therapeutic
      agents.

PMID- 17202598
TI  - Integrated Management of Neonatal and Childhood Illness (IMNCI): implementation
      challenges in India.

PMID- 17202600
TI  - Evaluation of simple clinical signs of illness in young infants (0-2 months) and
      its correlation with WHO IMCI algorithm (7 days to 2 months).
AB  - OBJECTIVE: To evaluate simple clinical signs of illness in young infants (0 to 2
      months) and to correlate with WHO IMCI algorithm (7 days-2 months). DESIGN:
      Prospective observational. Study conducted in the outpatient department and
      emergency room of a pediatric tertiary level hospital. METHODS: Four hundred and
      ninety seven young infants (0 to 2 months) presenting to outpatient department or
      emergency room were recruited. Detailed history, clinical examination including
      all signs in IMCI algorithm was recorded in the pre-designed proforma. The study
      subjects were investigated and managed according to the protocol of treating
      unit, which served as gold standard. The diagnostic and therapeutic agreement
      between the gold standard and IMCI was computed. The study subjects were analyzed
      as one age group (0 to 2 months) and also after de- segregating into early and
      late neonatal age group (0 to 7 days and 7 days to 2 months age). RESULTS: Mean
      number of illnesses in 0 to 7 days, 7 days-2 months and 0-2 months groups were
      1.97, 2.0 and 2.02 respectively. Those who required referral as per IMCI
      algorithm had higher proportion of co-morbidities. The referral criteria were
      fairly sensitive (78 to 85 percent) in predicting hospitalization with moderately
      high specificity (78 percent). Diagnostic agreement between gold standard and
      IMCI module was complete in 57 to 68 percent. Amongst diagnostic mismatch, under
      diagnosis was found more frequently (72 to 82 percent) than over-diagnosis (17 to
      29 percent). The sensitivity of algorithm to identify serious bacterial
      infections was quite high (96 to 98 percent) with moderately good specificity (80
      to 92 percent). Jaundice was single most important complaint accounting for 47 to
      62 percent of diagnostic mismatch. CONCLUSION: IMCI algorithm appears to be a
      promising, feasible and useful intervention strategy to triage and treat young
      infants in 7 days-2 months age group. This tool remains effective even when
      extended to 0 to 7 days age group. However a further increase in its sensitivity
      can be achieved by including yellowness of lower extremities/ palms/ soles as a
      criterion.

PMID- 17202599
TI  - Unusual clustering of diseases and manifestations in pediatric admissions of a
      tertiary care center.
AB  - BACKGROUND: Cluster investigations has been an important tool in investigations
      of diseases. While clustering of diseases or a manifestation in community can
      cause great public alarm, similar unexplained clustering in hospital admissions
      has baffled clinicians. OBJECTIVES: (a) To determine whether perceived
      unexplained clustering of diseases and manifestations among hospital admissions
      is real or significant. (b) To look for possible explanations of such clustering.
      DESIGN: One-year prospective observational and two-year retrospective study.
      MATERIAL AND METHODS: Cases admitted under pediatric and neonatal services
      (excluding rooming in babies) from September 2002 to August 2003 formed material
      for prospective and cases admitted for 2 years prior for retrospective study.
      Whenever an unexplained cluster of disease/manifestation was perceived, case
      definition was finalized and cases recorded. Retrospective cluster analysis was
      done for some significant unexplained clusters detected prospectively. These
      clusters case rate were analyzed in relation to age, sex, climatic conditions,
      etiology of case, etc. to detect any correlation. Pearson correlation
      coefficient, chi-square test, centroid method and Z test of proportion were used
      for statistical significance. RESULTS: Eight unexplained clusters were perceived
      in prospective study. 3 (hyperbilirubinemia in exchange range hypocalcemic
      seizures and vesicoureteric reflux) proved statistically not significant. 3 were
      small clusters of uncommon diseases / manifestations (biliary atresia,
      cardiomyopathy, and acral gangrene). Two large significant clusters, major non
      traumatic bleeding manifestations (MNTBM) and acute renal failure (ARF) occurred
      to which retrospective study was extended. Tmax and Tmin (average maximum and
      minimum daily temperature) had statistically significant positive correlation
      with ARF (gamma = + 0.83, P <0.001 for Tmax and gamma =+ 0.56, P = 0.002 for
      Tmin) and negative correlation with MNTBM (gamma = - 0.34, P = 0.040 for Tmax and
      gamma = - 0.59, P <0.001 for Tmin). Barometric pressure has significant negative
      and positive correlation with MNTBM and ARF respectively (gamma =+ 0.57, P <0.001
      for MNTBM and gamma = -0.45,P = 0.006 for ARF). The clusters also had significant
      positive correlations with female sex and age under 1 year (Z = 2.48, P
      <0.001,chi2=13.83, P<0.001 for sex and age of MNTBM and Z =3.11, P <0.001, chi2
      =10.85, P <0.001 forage and sex of ARF cases respectively). Three small clusters
      and a small subgroup of MNTBM(subcutaneous nodules as manifestations of bleeding
      disorders) occurred predominantly under one year and different sexes were
      involved. CONCLUSIONS: Several significant unexplained clustering were noted
      among hospital admissions. There was significant correlation with climatic
      conditions, age and sex. Larger, longer and multicentric studies in different
      geographical areas are required to investigate more plausible but complex
      biological phenomenon and associations related to diseases or manifestations.
      Cluster awareness has diagnostic and management implications for clinician as it
      also helps in early recognition of disease outbreak and dissemination of
      information and hospital staff to be prepared to handle increased number of cases
      and its treatment.

PMID- 17202601
TI  - Adherence issues in asthma.
AB  - In any chronic disease like asthma, the effectiveness of therapy depends on how
      good the treatment is and how well the patient takes it. Non-adherence maybe in
      form of omission of doses, incorrect medication, incorrect dosages or schedules,
      premature discontinuation of drugs, not following advice to avoid allergens and
      sub optimal inhalation technique. Unrecognized non-adherence decreases the
      effectiveness of asthma therapy. Non adherence can result in an increased rate of
      illness exacerbation, hospitalization, emergency department visits and asthma
      related deaths. One hundred sixty eight patients and their guardians on follow up
      in pediatric asthma clinic were administered a questionnaire regarding adherence
      to anti asthma therapy. Non adherence of different forms was seen in up to 68
      percent of patients. The purpose of this communication is to report the frequency
      of non adherence in patients with asthma and suggest remedial measures.

PMID- 17202602
TI  - Polio eradication strategies in Indian recommendations under IAP Action Plan
      2006.

PMID- 17202604
TI  - A comparative study of nonpharmacological methods to reduce pain in neonates.
AB  - A randomized study was done to compare non pharmacological methods to reduce the
      pain of heel pricks in 104 stable term neonates. Non-nutritive sucking (NNS),
      rocking, massage, sucrose (20 percent), distilled water (DW) and expressed breast
      milk (EBM) were used as pain reducing agents. Duration of cry and Douleur Aigue
      du Nouveau ne (DAN) score were used to assess pain. Physiological parameters were
      also recorded before and after the stimulus. At 30 seconds after the stimulus,
      the pain scores were lowest in the sucrose group but this was not sustained at 1,
      2 and 4 minutes. At 2 and 4 minutes pain scores were lowest in the NNS and
      rocking groups as compared to sucrose, distilled water, expressed breast milk and
      massage. The total duration of crying was also lowest in the NNS and rocking
      groups. Physiological parameters were comparable in all groups. Babies who were
      in Prechtl State 1 and 2 (sleeping) at the time of stimulus showed significantly
      lesser response to pain compared to babies who were awake. This was seen in all
      the intervention groups. In conclusion, our study suggests that rocking or giving
      a baby a pacifier are more effective non-pharmacological analgesics than EBM, DW,
      sucrose or massage for the pain of heel pricks in neonates. A calm or sleeping
      state before a painful procedure also appears to decrease crying and pain scores.

PMID- 17202603
TI  - Physical growth patterns and dental caries in thalassemia.
AB  - This study was conducted to assess the effect of age, ferritin level, hemoglobin
      level and chelating agents on the physical growth in thalassemic children and to
      determine the prevalence of dental caries in thalassemic children. Weight,
      standing height, sitting height and subischial leg length were measured in 65
      children attending the Thalassemia day care center at a tertiary hospital in
      Delhi. Their mean pre transfusion hemoglobin and ferritin levels over the
      previous two years were calculated. Dental caries indices, DMFT and DMFS were
      measured and compared with age matched controls. Weight, standing height, sitting
      height and subischial leg length expressed as percentage for age in children
      >or=10 y were significantly lower than those of children < 6 y, and those 6 to 10
      y. Mean hemoglobin and ferritin did not affect growth significantly. Sitting
      height for age in children receiving Desferrioxamine alone or Desferrioxamine
      with Deferiprone was significantly lower than that of children receiving
      Deferiprone alone or no chelating agent. Dental caries were significantly higher
      in thalassemics.

PMID- 17202605
TI  - Miltefosine in children with visceral leishmaniasis.
AB  - Sixty four children (38 boys and 26 girls), aged 1 yr to 14 yr, presenting with
      fever, splenomegaly and positive LD body in splenic smear examination, admitted
      to pediatric ward of Nalanda Medical college and Child care center between 1st
      July 03 to 30th June 04 were taken for study. Patients were categorized into two
      groups: 44 were in Group I (Patients who had not received prior antileishmanial
      drug) and 20 in Group II (Patients who had received 30 days course of SAG; 20 mg
      per kg per day). All patients were given Miltefosine in dose of 2.5 per kg per
      day od or bid per orally to a maximum of 100 mg and were followed at completion
      of therapy, 1 month and 6 months for clinical response, splenic size and parasite
      density. 63 patients had parasitological cure with relapse in one patient of
      Group I during follow up. One patient in Group II had no response with first
      course but became parasitologically negative with 2nd course of Miltefosine. In
      Group I, one patient had persistent splenomegaly and found to have associated
      portal hypertension. GI side effects i.e. diarrhea and vomiting were observed in
      26 and 23 patients respectively. Majority of patients had pancytopenia. Elevated
      ALT (> 3 times of normal) were seen in 28 and 11 patients of Group I and Group II
      respectively which returned to normal in subsequent follow up. The final cure
      rates were 93.2 percent and 95 percent in Groups I and II respectively.

PMID- 17202606
TI  - Molecular screening of the neutrophil elastase gene in congenital neutropenia.
AB  - Congenital neutropenia is a rare hematopoietic disease, which occurs sporadically
      or as an auto-somal dominant inherited disorder. Pathogenesis of congenital
      neutropenia can now be attributed to mutations of the ELA2 gene encoding
      neutrophil elastase. A child with severe congenital neutropenia with a
      heterozygous mutation G1887A in exon 2 of ELA2 gene is reported.

PMID- 17202607
TI  - Polyglandular autoimmune syndrome-type I.
AB  - Polyglandular autoimmune syndrome type I is a rare disorder characterized by
      mucocutaneous candidiasis (MC), hypoparathyroidism (HP) and adrenal insufficiency
      , requiring regular follow up as the components of the syndrome appear at
      different age groups. We report a six and half year boy having this syndrome and
      presenting with MC, HP and ectodermal dystrophy.

PMID- 17202608
TI  - Hodgkins lymphoma with HIV infection.
AB  - The association between Hodgkins Lymphoma (HL) with HIV is common in adults but
      rare in children. A 5 year old boy, known case of HIV on antiretroviral therapy,
      presented with prolonged fever, multiple enlarged lymph nodes along with
      hepatosplenomegaly. A diagnosis of Hodgkins lymphoma was entertained on
      histopathological examination; further subtyping was done by
      immunohistochemistry.

PMID- 17202609
TI  - Spring balance vs. SECA balance as a measure of weight in children.

PMID- 17202610
TI  - Body composition of preadolescents by skinfold measurements and Body Stat 1500
      Analyzer.

PMID- 17202611
TI  - Glanzmann thrombasthenia successfully operated for nasal deformation with
      recombinant factor VIIA.

PMID- 17202612
TI  - Polio eradication and the Indian Academy of Pediatrics.

PMID- 17202614
TI  - Incontinentia pigmenti.

PMID- 17202615
TI  - Determination of the recombination correction factor kS for some specific plane
      parallel and cylindrical ionization chambers in pulsed photon and electron beams.
AB  - It has been shown from an evaluation of the inverse reading of the dosemeter
      (1/M) against the inverse of the polarizing voltage (1/V), obtained with a number
      of commercially available ionization chambers, using dose per pulse values
      between 0.16 and 5 mGy, that a linear relationship between the recombination
      correction factor kS and dose per pulse (DPP) can be found. At dose per pulse
      values above 1 mGy the method of a general equation with coefficients dependent
      on the chamber type gives more accurate results than the Boag method. This method
      was already proposed by Burns and McEwen (1998, Phys. Med. Biol. 43 2033) and
      avoids comprehensive and time-consuming measurements of Jaffe plots which are a
      prerequisite for the application of the multi-voltage analysis (MVA) or the two
      voltage analysis (TVA). We evaluated and verified the response of ionization
      chambers on the recombination effect in pulsed accelerator beams for both photons
      and electrons. Our main conclusions are: (1) The correction factor k(S) depends
      only on the DPP and the chamber type. There is no influence of radiation type and
      energy. (2) For all the chambers investigated there is a linear relationship
      between kS and DPP up to 5 mGy/pulse, and for two chambers we could show
      linearity up to 40 mGy/pulse. (3) A general formalism, such as that of Boag,
      characterizes chambers exclusively by the distance of the electrodes and gives a
      trend for the correction factor, and therefore (4) a general formalism has to
      reflect the influence of the chamber construction on the recombination by the
      introduction of chamber-type dependent coefficients.

PMID- 17202616
TI  - A high-resolution anthropomorphic voxel-based tomographic phantom for proton
      therapy of the eye.
AB  - Proton therapy is increasingly used in medical treatments for cancer patients due
      to the sharp dose conformity offered by the characteristic Bragg peak. Proton
      beam interactions with the eye will be simulated using the MCNPX Monte Carlo code
      and available nuclear cross-section data to calculate the dose distribution in
      the eye gel and surrounding organs. A high-resolution eye model will be employed
      using a 3D geometrical voxel-based anthropomorphic head phantom obtained from the
      Visible Human Project (female data). Manual segmentation of the eye, carried out
      by the Medical Physics group at the University of Surrey resulted in 15
      identified structures. This work emphasizes the use of a realistic phantom for
      accurately predicting dose deposition by protons.

PMID- 17202617
TI  - Simultaneous determination of equivalent dose to organs and tissues of the
      patient and of the physician in interventional radiology using the Monte Carlo
      method.
AB  - This study presents the results of computations of organ equivalent doses and
      effective doses for the patient and the primary physician during an
      interventional cardiological examination. The simulations were carried out for
      seven x-ray spectra (between 60 kVp and 120 kVp) using the Monte Carlo code MCNP.
      The voxel-based whole-body model VIP-Man was employed to represent both the
      patient and the physician, the former lying on the operation table while the
      latter standing 15 cm from the patient at about waist level behind a lead apron.
      The x-rays, which were generated by a point source positioned around the table
      and were directed with a conical distribution, irradiated the patient's heart
      under five major projections used in a coronary angiography examination. The mean
      effective doses under LAO45, PA, RAO30, LAO45/CAUD30 and LLAT irradiation
      conditions were calculated as 0.092, 0.163, 0.161, 0.133 and 0.118 mSv/(Gy cm2)
      for the patient and 1.153, 0.159, 0.145, 0.164 and 0.027 microSv/(Gy cm2) for the
      shielded physician. The effective doses for the patient determined in this study
      were usually lower than the literature data obtained through measurements and/or
      calculations and the discrepancies could be attributed to the fact that this
      study computes the effective doses specific to the VIP-Man body model, which
      lacks an ovarian contribution to the gonadal equivalent dose. The effective doses
      for the physician agreed reasonably well with the literature data.

PMID- 17202618
TI  - Automatic detection of retinal anatomy to assist diabetic retinopathy screening.
AB  - Screening programmes for diabetic retinopathy are being introduced in the United
      Kingdom and elsewhere. These require large numbers of retinal images to be
      manually graded for the presence of disease. Automation of image grading would
      have a number of benefits. However, an important prerequisite for automation is
      the accurate location of the main anatomical features in the image, notably the
      optic disc and the fovea. The locations of these features are necessary so that
      lesion significance, image field of view and image clarity can be assessed. This
      paper describes methods for the robust location of the optic disc and fovea. The
      elliptical form of the major retinal blood vessels is used to obtain approximate
      locations, which are refined based on the circular edge of the optic disc and the
      local darkening at the fovea. The methods have been tested on 1056 sequential
      images from a retinal screening programme. Positional accuracy was better than
      0.5 of a disc diameter in 98.4% of cases for optic disc location, and in 96.5% of
      cases for fovea location. The methods are sufficiently accurate to form an
      important and effective component of an automated image grading system for
      diabetic retinopathy screening.

PMID- 17202619
TI  - In vivo EIS characterization of tumour tissue properties is dominated by excess
      extracellular fluid.
AB  - Electrical impedance spectroscopy (EIS) is a non-ionizing, non-invasive technique
      which can be used to detect the presence of malignant tumours based on their
      electrical properties. Although it has been suggested that the edema which
      accompanies tumours strongly influences EIS tumour characterization, such
      information has not, until now, been documented in the literature. Growing
      intramuscular rodent tumours were imaged using magnetic resonance imaging (MRI)
      and EIS at several time points post-tumour implantation. The amount of edema
      associated with the tumours was calculated from the MRI images. Electrical
      parameters (resistivity, permittivity, fluid index ratio and peak frequency) were
      extracted from the EIS spectra. Taken together, the resulting electrical
      parameters strongly indicate that edema is the dominating pathological feature in
      EIS characterization and can at times conceal the presence of the tumour.
      Receiver operating characteristic analysis supports these findings.

PMID- 17202620
TI  - Evaluation of the reproducibility of lung motion probability distribution
      function (PDF) using dynamic MRI.
AB  - Treatment planning based on probability distribution function (PDF) of patient
      geometries has been shown a potential off-line strategy to incorporate organ
      motion, but the application of such approach highly depends upon the
      reproducibility of the PDF. In this paper, we investigated the dependences of the
      PDF reproducibility on the imaging acquisition parameters, specifically the scan
      time and the frame rate. Three healthy subjects underwent a continuous 5 min
      magnetic resonance (MR) scan in the sagittal plane with a frame rate of
      approximately 10 f s-1, and the experiments were repeated with an interval of 2
      to 3 weeks. A total of nine pulmonary vessels from different lung regions (upper,
      middle and lower) were tracked and the dependences of their displacement PDF
      reproducibility were evaluated as a function of scan time and frame rate. As
      results, the PDF reproducibility error decreased with prolonged scans and
      appeared to approach equilibrium state in subjects 2 and 3 within the 5 min scan.
      The PDF accuracy increased in the power function with the increase of frame rate;
      however, the PDF reproducibility showed less sensitivity to frame rate presumably
      due to the randomness of breathing which dominates the effects. As the key
      component of the PDF-based treatment planning, the reproducibility of the PDF
      affects the dosimetric accuracy substantially. This study provides a reference
      for acquiring MR-based PDF of structures in the lung.

PMID- 17202621
TI  - Distinguishability for magnetic resonance-electrical impedance tomography (MR
      EIT).
AB  - A distinguishability measure is defined for magnetic resonance-electrical
      impedance tomography (MR-EIT) based on magnetic flux density measurements. This
      general definition is valid for 2D and 3D structures of any shape. As a specific
      case, a 2D cylindrical body with concentric inhomogeneity is considered and a
      bound of the distinguishability is analytically formulated. Distinguishabilities
      obtained with potential and magnetic flux density measurements are compared.

PMID- 17202622
TI  - Two-dimensional multi-level strain estimation for discontinuous tissue.
AB  - A large number of the strain estimation methods presented in the literature are
      based on the assumption of tissue continuity that establishes a continuous
      displacement field. However, in certain locations in the body such as the
      arteries in vivo scanning may produce displacement fields that are discontinuous
      between the two walls of the artery. Many of the displacement or strain
      estimators fail when the displacement fields are discontinuous. In this paper, we
      present a new 2D multi-level motion or displacement tracking method for accurate
      estimation of the strain in these situations. The final high-resolution
      displacement estimate is obtained using two processing steps. The first step
      involves an estimation of a coarse displacement estimate utilizing B-mode or
      envelope signals. To reduce computational time, the coarse displacement estimates
      are obtained starting from down-sampled B-mode pre- and post-compression image
      pairs using a pyramidal processing approach. The coarse displacement estimate
      obtained from the B-mode data is used to guide the final 2D cross-correlation
      computations on radio-frequency (RF) data. Results from finite element
      simulations and in vivo experimental data demonstrate the feasibility of this
      approach for imaging tissue with discontinuous displacement fields.

PMID- 17202623
TI  - Statistical reconstruction for x-ray CT systems with non-continuous detectors.
AB  - We analyse the performance of statistical reconstruction (SR) methods when
      applied to non-continuous x-ray detectors. Robustness to projection gaps is
      required in x-ray CT systems with multiple detector modules or with defective
      detector pixels. In such situations, the advantage of statistical reconstruction
      is that it is able to ignore missing or faulty pixels and that it makes optimal
      use of the remaining line integrals. This potentially obviates the need to fill
      the sinogram discontinuities by interpolation or any other approximative pre
      processing techniques. In this paper, we apply SR to cone beam projections of (i)
      a hypothetical modular detector micro-CT scanner and of (ii) a system with
      randomly located defective detector elements. For the modular-detector system, SR
      produces reconstruction volumes free of noticeable gap-induced artefacts as long
      as the location of detector gaps and selection of the scanning range provide
      complete object sampling in the central imaging plane. When applied to randomly
      located faulty detector elements, SR produces images free of substantial ring
      artefacts even for cases where defective pixels cover as much as 3% of the
      detector area.

PMID- 17202624
TI  - Evaluation of x-ray diffraction enhanced imaging in the diagnosis of breast
      cancer.
AB  - The significance of the x-ray diffraction enhanced imaging (DEI) technique in the
      diagnosis of breast cancer and its feasibility in clinical medical imaging are
      evaluated. Different massive specimens including normal breast tissues, benign
      breast tumour tissues and malignant breast tumour tissues are imaged with the DEI
      method. The images are recorded respectively by CCD or x-ray film at different
      positions of the rocking curve and processed with a pixel-by-pixel algorithm. The
      characteristics of the DEI images about the normal and diseased tissues are
      compared. The rocking curves of a double-crystal diffractometer with various
      tissues are also studied. The differences in DEI images and their rocking curves
      are evaluated for early diagnosis of breast cancers.

PMID- 17202625
TI  - Pixel-by-pixel deconvolution of bolus-tracking data: optimization and
      implementation.
AB  - Quantification of haemodynamic parameters with a deconvolution analysis of bolus
      tracking data is an ill-posed problem which requires regularization. In a
      previous study, simulated data without structural errors were used to validate
      two methods for a pixel-by-pixel analysis: standard-form Tikhonov regularization
      with either the L-curve criterion (LCC) or generalized cross validation (GCV) for
      selecting the regularization parameter. However, problems of image artefacts were
      reported when the methods were applied to patient data. The aim of this study was
      to investigate the nature of these problems in more detail and evaluate
      strategies of optimization for routine application in the clinic. In addition we
      investigated to which extent the calculation time of the algorithm can be
      minimized. In order to ensure that the conclusions are relevant for a larger
      range of clinical applications, we relied on patient data for evaluation of the
      algorithms. Simulated data were used to validate the conclusions in a more
      quantitative manner. We conclude that the reported problems with image quality
      can be removed by appropriate optimization of either LCC or GCV. In all examples
      this could be achieved with LCC without significant perturbation of the values in
      pixels where the regularization parameter was originally selected accurately. GCV
      could not be optimized for the renal data, and in the CT data only at the cost of
      image resolution. Using the implementations given, calculation times were
      sufficiently short for routine application in the clinic.

PMID- 17202626
TI  - Performance comparison of six independent components analysis algorithms for
      fetal signal extraction from real fMCG data.
AB  - In this study we compare the performance of six independent components analysis
      (ICA) algorithms on 16 real fetal magnetocardiographic (fMCG) datasets for the
      application of extracting the fetal cardiac signal. We also compare the
      extraction results for real data with the results previously obtained for
      synthetic data. The six ICA algorithms are FastICA, CubICA, JADE, Infomax, MRMI
      SIG and TDSEP. The results obtained using real fMCG data indicate that the
      FastICA method consistently outperforms the others in regard to separation
      quality and that the performance of an ICA method that uses temporal information
      suffers in the presence of noise. These two results confirm the previous results
      obtained using synthetic fMCG data. There were also two notable differences
      between the studies based on real and synthetic data. The differences are that
      all six ICA algorithms are independent of gestational age and sensor
      dimensionality for synthetic data, but depend on gestational age and sensor
      dimensionality for real data. It is possible to explain these differences by
      assuming that the number of point sources needed to completely explain the data
      is larger than the dimensionality used in the ICA extraction.

PMID- 17202627
TI  - Laser-assisted cryosurgery of prostate: numerical study.
AB  - A new methodology for preventing freezing damage beyond pre-specified boundaries
      during prostate cryosurgery is proposed herein. It consists of emitting
      controlled laser irradiation from the urethra, across the wall and into the
      prostate while conventional cryoprobes freeze the unwanted prostate tissue. The
      purpose of this methodology is to protect the urethral wall better and confine
      the desired cryoinjured region more accurately than the current cryosurgery
      approach. We also explore the potential use of light-absorbing dyes to further
      enhance the laser light absorption and corresponding heat generation to increase
      the thickness of the protected region. A finite difference heat diffusion model
      in polar coordinates with temperature-dependent thermophysical properties
      simulates the prostate freezing while laser irradiation across the urethral wall
      is emitted. This approach maintains the temperature of the urethral wall and the
      adjacent tissue above a pre-specified threshold temperature of -45 degrees C,
      independent of application time. Temperature contours resulting from prostate
      cryoablation with (a) conventional constant temperature heating; (b) laser
      irradiation heating; and (c) laser irradiation heating with pre-injected light
      absorbing dye layers indicate that the thickness of the protected region
      increases in this order, and that the latter two methodologies may be more
      effective in limiting cryoinjury to a predefined region compared to constant
      temperature heating. An analysis of laser power requirements and sensibility of
      laser-assisted cryosurgery (LAC) of prostate is also presented. It is shown that
      tissue temperature may vary as much as +/-20 degrees C with variations of +/-10%
      in laser power relative to the nominal power required to maintain the tissue at
      37 degrees C. This demonstrates the sensitivity to laser power and the need of an
      accurate laser power control algorithm.

PMID- 17202628
TI  - Direct-aperture optimization applied to selection of beam orientations in
      intensity-modulated radiation therapy.
AB  - Direct-aperture optimization (DAO) was applied to iterative beam-orientation
      selection in intensity-modulated radiation therapy (IMRT), so as to ensure a
      realistic segmental treatment plan at each iteration. Nested optimization engines
      dealt separately with gantry angles, couch angles, collimator angles, segment
      shapes, segment weights and wedge angles. Each optimization engine performed a
      random search with successively narrowing step sizes. For optimization of segment
      shapes, the filtered backprojection (FBP) method was first used to determine
      desired fluence, the fluence map was segmented, and then constrained direct
      aperture optimization was used thereafter. Segment shapes were fully optimized
      when a beam angle was perturbed, and minimally re-optimized otherwise. The
      algorithm was compared with a previously reported method using FBP alone at each
      orientation iteration. An example case consisting of a cylindrical phantom with a
      hemi-annular planning target volume (PTV) showed that for three-field plans, the
      method performed better than when using FBP alone, but for five or more fields,
      neither method provided much benefit over equally spaced beams. For a prostate
      case, improved bladder sparing was achieved through the use of the new algorithm.
      A plan for partial scalp treatment showed slightly improved PTV coverage and
      lower irradiated volume of brain with the new method compared to FBP alone. It is
      concluded that, although the method is computationally intensive and not suitable
      for searching large unconstrained regions of beam space, it can be used
      effectively in conjunction with prior class solutions to provide individually
      optimized IMRT treatment plans.

PMID- 17202629
TI  - Optimization of tumour control probability in hypoxic tumours by radiation dose
      redistribution: a modelling study.
AB  - Tumour hypoxia is a known cause of clinical resistance to radiation therapy. The
      purpose of this work was to model the effects on tumour control probability (TCP)
      of selectively boosting the dose to hypoxic regions in a tumour, while keeping
      the mean tumour dose constant. A tumour model with a continuous oxygen
      distribution, incorporating pO(2) histograms published for head and neck
      patients, was developed. Temporal and spatial variations in the oxygen
      distribution, non-uniform cell density and cell proliferation during treatment
      were included in the tumour modelling. Non-uniform dose prescriptions were made
      based on a segmentation of the tumours into four compartments. The main findings
      were: (1) Dose redistribution considerably improved TCP for all tumours. (2) The
      effect on TCP depended on the degree of reoxygenation during treatment, with a
      maximum relative increase in TCP for tumours with poor or no reoxygenation. (3)
      Acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells
      gave large reductions in TCP. (4) Restricted dose redistribution still gave a
      substantial increase in TCP as compared to uniform dose boosts. In conclusion,
      redistributing dose according to tumour oxygenation status might increase TCP
      when the tumour response to radiotherapy is limited by chronic hypoxia. This
      could potentially improve treatment outcome in a subpopulation of patients who
      respond poorly to conventional radiotherapy.

PMID- 17202630
TI  - Calculation of 10 MV x-ray spectra emitted by a medical linear accelerator using
      the BFGS quasi-Newton method.
AB  - To calculate photon spectra for a 10 MV x-ray beam emitted by a medical linear
      accelerator, we performed numerical analysis using the aluminium transmission
      data obtained along the central axis of the beam under the narrow beam condition
      corresponding to a 3x3 cm2 field at a 100 cm distance from the source. We used
      the BFGS quasi-Newton method based on a general nonlinear optimization technique
      for the numerical analysis. The attenuation coefficients, aluminium thicknesses
      and measured transmission data are necessary inputs for the numerical analysis.
      The calculated x-ray spectrum shape was smooth in the lower to higher energy
      regions without any angular components. The x-ray spectrum acquired by the
      employed method was evaluated by comparing the measurements along the central
      axis percentage depth dose in a water phantom and by a Monte Carlo simulation
      code, the electron gamma shower code. The values of the calculated percentage
      depth doses for a 10x10 cm2 field at a 100 cm source-to-surface distance in a
      water phantom were obtained using the same geometry settings as those of the
      water phantom measurement. The differences in the measured and calculated values
      were less than +/-1.0% for a broad region from the shallow part near the surface
      to deep parts of up to 25 cm in the water phantom.

PMID- 17202631
TI  - Dose distribution for endovascular brachytherapy using Ir-192 sources: comparison
      of Monte Carlo calculations with radiochromic film measurements.
AB  - An analysis of Ir-192 source distribution using the Monte Carlo method and
      radiochromic film experiments for endovascular brachytherapy is presented. Three
      different source possibilities, namely, mHDR Ir-192 sources with 5 mm and 2.5 mm
      step sizes and Ir-192 seed sources with 1 mm air gap are investigated to obtain
      uniform radial dose distribution throughout the treatment area. From this study,
      it is inferred that mHDR Ir-192 sources with 2.5 mm step size are effective for
      getting dose uniformity. Hence, different restenosis geometries, namely, linear,
      dumb bell and hairpin, are simulated with 2.5 mm step size, 15 mHDR Ir-192
      sources using the Monte Carlo technique and the results are compared
      experimentally by using radiochromic films. The results from both methods agreed
      to within 7%. Further, it is also inferred that for the dosimetry of endovascular
      brachytherapy, the film dosimetry may be considered adequate, even if the film
      calibration is time consuming and requires adequate dosimetric procedures.

PMID- 17202632
TI  - Topiramate as a new antiepileptic drug in epileptic children in Iran.
AB  - OBJECTIVE: It is known that current antiepileptic drugs cannot control seizures
      in 20-30% of patients. The aim of this study was to evaluate the efficacy and
      safety of topiramate (TPM) as add-on therapy in intractable epileptic children in
      Iran. METHODS: As a quasi- experimental (before and after) study, 42 iranian
      children aged 1-15 years, 28 boys and 14 girls with refractory seizures seeking
      treatment were recruited to be subjects of this study. RESULTS: Type of seizures
      of those 42 epileptic children were as follows: L.G.S (n=14), idiopathic epilepsy
      (n=8), symptomatic epilepsy (n=16) and progressive myoclonic epilepsy (n=4). At
      the end of three months of treatment in which topiramate was used concomitantly
      with previous AED, 17% became seizure free, 26% had more than 50% reduction of
      seizure frequency and 5% of them had increasing seizures. Therefore, the drug is
      statistically significant in seizures reduction. The efficacy of the drug was
      statistically significant in idiopathic and symptomatic epilepsy. The author's
      did not notice any serious side effects such as: hematologic abnormality,
      hepatotoxicity and nephrotoxicity. CONCLUSION: This study supports efficacy and
      safety of TPM in controlling of intractable epilepsy in children and indicates
      the drug should be considered as an add-on therapy in the management of
      refractory epileptic syndromes.

PMID- 17202633
TI  - Miltefosine in children with visceral leishmaniasis: a prospective, multicentric,
      cross-sectional study.
AB  - OBJECTIVE: Miltefosine, an alkyl phospholipid has been found effective against
      visceral leishmaniasis (VL) in adults in various studies. The authors safety,
      tolerance and efficacy of Miltefosine and compared with available gold standard
      anti-Ieishmanial drug, Amphotericin B, a parenteral formulation in children with
      VL. METHODS: All consecutive children aged 1 yr to 14 yr, presented with fever,
      splenomegaly and positive LD body in splenic smear examination, admitted in
      pediatric ward of Nalanda Medical college and Child care center between 1st July
      03 to 30th June 05 were taken for study. Patients were randomized into four
      groups. Group-l and 2 patients were given Miltefosine in dose of 2.5 mg/Kg day
      o.d. or b.i.d. per orally to a maxiIpum of 100 mg and group 3 and 4 Amphotericin
      B at a dose of 1 mg/Kg/day (total: 15 mg/Kg). All patients were followed at
      completion of therapy, 3 months and 6 months for clinical response, splenic size
      and parasitologically. RESULTS: Out of 125 children, 44 were in group-I, 20 in
      group-2, 38 in group-3 and 23 in group- 4, 124 patients had parasitological cure
      with relapse in one patient of group 1 during follow up. One patient in-group II
      had no response with first course but became parasitologically negative with 2nd
      course of Miltefosine. In-group I, one patient had persistent splenomegaly and
      found to have associated portal hypertension. Final cure rate with Miltefosine
      and Amphotericin B was 93.2%, 95%, 92.1% and 91.3% in-group 1, 2, 3 and 4
      respectively, which are statistically insignificant. Majority of patients had
      pancytopenia. Eievated". AL T (>3 times of normal) were seen in 28, 11, 19 and 13
      patients of group 1, 2, 3 and group 4 respectively which returned to normal in
      subsequent follow up. Raised BUN was observed more in patients who got
      Amphotericin B i.e. 65.42% and 73.91 % in-group 3 and 4 respectively. GI side
      effects i.e. diarrhea and vomiting were observed in 26 and 23 patients in-group 1
      and 2 respectively. CONCLUSION: Miltefosine is safe, well tolerable, and highly
      effective and has same efficacy as Amphotericin B in newly diagnosed and SAG
      resistant children with visceral leishmaniasis.

PMID- 17202634
TI  - Parasitic etiology of childhood diarrhea.
AB  - The objective was to determine the prevalence of parasitic agents among under
      five children with diarrhea in Ilesa, Nigeria and the clinical correlates of
      diarrhea associated with parasitic infestation. All under-five children
      presenting with diarrhea in the hospital had stool microscopic examination.
      Children with parasites in diarrheic stools (cases) were compared with those
      without (controls) for clinical features. Out of 300 under-five children with
      diarrhea, 70 (23.3%) had parasites. There were 18 (6%) helminthes and 52 (17.3%)
      protozoas. These included the' ova of Ascaris lumbricoides (13; 18.6%), cysts and
      trophozoites of Entamoeba. histolytica (46; 65.7%), cysts of Entamoeba coli (1;
      1.4%), Giardia Lamblia (5; 7.1%), Necator american us (1; 1.4%) and Trichuris
      trichiuria (4; 5.7%). As against the controls, the cases were older (t = 4.88; p
      = 0:0000017), more undernourished (OR = 2.04; 95% CI = 1.14 to 3.63; p = 0.009)
      and belonged to the lower socio-economic classes (OR = 7.15; 95% CI = 3.83 to
      13.43; p=0.0000). It is concluded that parasitic infestations are commonly
      associated with childhood diarrhoea in Nigeria. Malnutrition and low socio
      economic status are risk factors.

PMID- 17202635
TI  - Apnea in infants.
AB  - OBJECTIVE: The main objective of this study was to describe frequency of risk
      factors in newborns who present different types of apnea in polysomnographic
      (PSG) recordings in neonatal care units. METHODS: The study was carried out in
      neonatal care units of a perinatal tertiary level institution in Mexico City
      between August 2002 and August 2003. Infants were selected from among 223 infants
      if they presented any type of apnea event in sleep PSG recordings. RESULTS:
      Nearly 25% of patients from a neonatal care unit presented apnea events. Infants
      with apnea showed lower values of age, weight, and cephalic perimeter at birth
      than infants without apnea, but did not show more neurologic risk factors.
      Central apnea events were more frequent in infants with preterm birth
      (birthweight < 1,500 g), obstructive apnea events were observed in infants with
      hyperbilirubinemia and gastro-esophageal reflux, while mixed events were seen in
      infants with sepsis, and hyperbilirubinemia. Sleep PSG recordings detected that
      36% of infants with apnea have no previous clinic suspicion of the problem.
      CONCLUSION: Central events of apnea were found more frequent in infants with
      preterm birth, obstructive events in newborns with hyperbilirubinemia and
      gastroesophagic reflux, while infants mixed apnea had more frequent
      hyperbilirubinemia and sepsis.

PMID- 17202636
TI  - Study of growth in prepubertal asthmatics.
AB  - OBJECTIVE: The aim of this pilot study was to assess whether long standing asthma
      affects growth in prepubertal Egyptian children before initiation of long-term
      corticosteroid therapy. METHODS: Children with asthma were divided into two
      groups according to asthma severity, moderate (n=24) and severe (n=14) and were
      compared for their physical and skeletal growth with a control group (n=15) using
      standard deviation score (SDS) and one-way ANOVA (analysis of variance) test.
      RESULTS: No statistically significant differences were found between various
      growth parameters (weight, height, BMI, upper segment lower segment ratio, and
      skin fold thickness in asthmatic and normal children, although a positive
      correlation was found between the age at which the asthma presented and the
      height in all asthmatic children, r= 0.288, p= 0.036. The bone age standard
      deviation scores (SDS) were 0.97 mean, -0.165 and -0.572 for controls, moderate
      and severe asthmatics respectively (P< 0.05), and significant inter group
      difference between the 2 asthmatic groups (moderate and severe) and the controls
      was found. CONCLUSION: The authors conclude that there was no significant major
      effect of asthma per se on growth parameters in children, but that skeletal
      maturation was influenced by long standing asthma.

PMID- 17202637
TI  - Congenital CMV infection in symptomatic infants in Delhi and surrounding areas.
AB  - Many viral infections are associated with significant maternal and fetal
      consequences during pregnancy among which cytomegalovirus is one of the most
      important agent, globally. Both primary and recurrent infection due to this virus
      can result in fetal infection. Samples from Congenital Anoammaled babies are
      referred to NICD from Delhi based Government hospitals and surrounding areas for
      diagnosis of congenital infections like Toxoplasm, Rubella, CMV and Herpes. In
      the present study, accumulated data is presented for the most common teratogenic
      virus--Cytomegalovirus prevalence as a causative agent for congenital infection
      in New Born babies at Delhi and surrounding areas. 96 samples from symptomatic
      babies in the age group of few days to 6 months exhibiting different congenital
      anomalies, were reported between 1 st Jan 04 to 30 th April/05. All the blood
      samples were tested for the detection of CMV (IgM) antibodies using m-capture
      ELISA technique. 18(18.75%) samples from babies showed positive titres for CMV
      IgM antibodies. None of the mothers of positive babies were found positive for
      CMV-IgM antibodies but all were serologically exposed to CMV virus previously as
      their serum samples were positive for CMV-IgG antibodies indicating primary
      infection in the past or reactivation/reinfection with a different strain of CMV
      in the early pregnancy.

PMID- 17202638
TI  - Attitude and knowledge of high school pupils towards adolescents with special
      needs (Tourette's syndrome).
AB  - OBJECTIVE: To determine high school pupils' attitudes towards adolescents with
      special needs (for example: TS); to learn what they know about the symptomatology
      and the exceptional behavior of TS; and what they think about their social
      future. METHODS: Ninety-nine pupils participated in the study. Their mean age was
      16.7 +/- 0.8 years. Forty-eight point five percent were boys, and the rest girls.
      They completed a questionnaire concerning knowledge and attitudes towards
      adolescents with special needs (diagnosed as TS). They had participated in
      lessons and class talks about handicapped children with psycho- behavioral
      symptoms. RESULTS: The scores for their knowledge were at a level of 68.9%. Half
      of the pupils knew and responded correctly that TS was of genetic origin; but the
      most important: they expressed a comprehensive and tolerant attitude towards
      impaired behavior in TS at a level of 55.3%. The tolerant attitude increased with
      advancing age and with school grades. The attitudes were more comprehensive in
      families suffering form their own emotional or other psychiatric difficulties.
      Forty-three point four percent of pupils understand and consider TS to be an
      emotional, behavioral and psychiatric entity. Sixty-two point six percent of
      pupils understand as well and believe that the disruptive behavior and outbursts
      in TS are involuntary and not under the adolescent's control. On the other hand,
      a quarter of the pupils see justification for repeated punishment of TS
      adolescents for their impaired behavior. Fifty-six point six percent of regular
      pupils were ready to develop friendship with TS classmates in spite of their
      unexpected and unruly behaviour. Eight-three point eight percent of pupils
      believe it is better to inform teachers and classmates about the impaired
      behavior of these TS adolescents. Concerning the future of these disabled
      adolescents, pupils scored a level of 44% for their optimistic beliefs about
      success in future life; 52% believe that in spite of all difficulties TS
      adolescents would be able to live an ordinary life, to raise a family and to
      work. CONCLUSIONS: It is crucial to improve pupils' attitudes in schools (as well
      as their teachers') towards adolescents with special needs (including TS). The
      authors recommend that TS be considered as a neuro-behavioral and psychiatric
      disorder; it should be considered as a disability, which calls for comprehension,
      (not punishment). It would also be of value to speak in classes about the
      handicaps and neurobehavioral limitations for example of these TS adolescents, as
      well as about other pupils in school with special needs, in order to behave
      socially correctly towards them. The final aim will be that pupils in school will
      learn to accept the different child and adolescent as they are.

PMID- 17202639
TI  - Progressive facial disfigurement and deafness in craniometaphyseal dysplasia.

PMID- 17202640
TI  - Unusual K-wire migration.
AB  - The authors report a case of intra-abdominal migration of a Kirschner wire from
      the left hip to the right lobe of the liver in a 5-year-old child. The wire was
      used for stabilization of the left hip after open reduction for neglected
      unreduced congenital dislocation of the left hip. The migrated wire was removed
      by laparotomy. Surprisingly, no injury was noted to any intervening abdominal
      structure intra-operatively. This unusual migration of a Kirschner wire into a
      child's liver has not been reported previously.

PMID- 17202641
TI  - Hyperekplexia in two siblings.
AB  - Hyperekplexia is a rare, hereditary, non-epileptic disorder characterized by an
      exaggerated startle reaction to unexpected auditory, somatosensory and visual
      stimuli. The authors describe a one-day-old term neonate, who presented with
      jitteriness and episodic tonic spasms, and his elder sister with hyperekplexia.
      Hyperekplexia though is a rare disorder is one of the differential diagnoses for
      refractory tonic spasms in infancy. The prognosis is generally good in hereditary
      hyperekplexia. Recent molecular studies have revealed many associated mutations
      in the glycine receptor alpha and beta subunit genes.

PMID- 17202642
TI  - Mitochondrial neuro-gastrointestinal encephalopathy syndrome.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy is a rare disorder
      affecting the pediatric age group with a heterogeneous multisystem involvement.
      We happen to manage a young child with symptoms of constipation since infancy
      along with cachexia, seizures and peripheral neuropathy. The child later went
      into encephalopathy preterminally. This clinical syndrome fitted very well with
      mitochondrial neurogastrointestinal encephalomyopathy. The child had elevated
      lactate levels and electron microscopy of the rectal biopsy was suggestive of a
      mitochondrial disorder To the best of our knowledge there is no case report of
      this syndrome from India and since this presents with diagnostic difficulties so
      is being reported.

PMID- 17202643
TI  - Asphyxiating thoracic dystrophy with facial dysmorphism.
AB  - Here it is reported a male newborn baby with features of asphyxiating thoracic
      dystrophy (ATD) with facial dysmorphism. The disproportionate rhizomelic short
      stature, narrow thorax, long fibulae, wide metaphysis and trident acetabule are
      consistent with diagnosis of ATD. In addition the baby had facial dysmorphism and
      broad thumbs and great toes similar to Oto-palato-digital syndrome type II (OPD
      II). The association of these features with ATD is not reported till date.

PMID- 17202645
TI  - Congenital intrahepatic portosystemic shunt--an incidental rare anomaly.
AB  - Congenital intrahepatic shunts are rare anomalies that are usually incidental in
      a child who undergoes an ultrasound examination for some other reasons. Early
      diagnosis is important, because the condition can lead to hepatic encephalopathy
      and hypoglycemia. Author's would like to describe the findings of one such
      patient diagnosed to be having congenital intrahepatic shunt and discuss the
      clinical importance of this condition.

PMID- 17202644
TI  - Subacute sclerosing panencephalitis presenting as acute disseminated
      encephalomyelitis.
AB  - Subacute sclerosing panencephalitis (SSPE) is a chronic encephalitis of childhood
      and young adolescence due to persistent measles virus infection of the central
      nervous system. In majority of cases onset occurs from 5-15 years of age. In a
      nonimmunized population the average onset is 8 years. Children with SSPE had
      experienced natural infection with the rubeola virus at an early age, half before
      age 2 years. SSPE generally occurs 5-10 years after measles infection. In the
      early stages of the disease behavioral and personality changes is followed by
      myoclonic jerks and convulsions. In late stages dementia, stupor and coma
      develops. Diagnosis is achieved by typical clinical findings, measles antibody
      titer increase in cerebrospinal fluid (CSF) and serum, high amplitude, slow,
      sharp waves in EEG. Prognosis is poor and death ensues in about 3 yr after the
      diagnosis. Here it is presented a 7-years-old boy with involuntary movements in
      both hands, drop attacks while walking, ataxia and stupor. Due to suggestive
      radiological and clinical findings and a history of recent mumps infection he was
      thought to have acute disseminated encephalomyelitis initially and given
      treatment. But due to clinical deterioration and detection of anti measles IgG in
      serum and CSF, SSPE diagnosis was confirmed. With this SSPE case presenting
      initially as ADEM, the authors tried to emphasize that presentation of SSPE may
      clinically and radiologically be diverse and a thorough differential diagnosis is
      mandatory for a definite diagnosis.

PMID- 17202646
TI  - Rhabdomyolysis caused by hypernatremia.
AB  - Rhabdomyolysis is a clinical picture which is rarely seen in children. In this
      case report here it is presented a patient who has biochemical and clinical signs
      of rhabdomyolysis and admitted to our clinic with hypernatremia. The authors
      think that it is necessary to be alert for rhabdomyolysis in severe hypernatremia
      cases.

PMID- 17202647
TI  - Idiopathic neonatal aortic thrombosis.
AB  - We report a term neonate with severe aortic thrombosis involving the aorto-iliac
      segment and leading to renal failure. This patient did not have any predisposing
      risk factors. The authors have also reviewed the literature on neonatal aortic
      thrombosis and discuss the need for evolving evidence based consensus guidelines
      for management of this catastrophe.

PMID- 17202648
TI  - Pulmonary endarteritis.
AB  - Pulmonary arterial endarteritis is a rare event even in patients with congenital
      heart disease. In this paper, the authors report two cases of pulmonary
      endarteritis diagnosed at autopsy. The first was a 3-month-old male infant with
      absence of congenital heart defect (who had had neonatal sepsis). This patient
      presented with pneumonia and succumbed within 36 hours of hospital stay despite
      appropriate antimicrobial therapy and supportive management. The second patient
      was a 13-month-old male child with previously undiagnosed tetralogy of Fallot who
      had clinical presentation of acute meningitis with convulsions and succumbed
      within 12 hours of hospital stay despite adequate treatment. The main autopsy
      findings were chronic arteritis of the pulmonary trunk and right pulmonary artery
      in the former and rupture of the pulmonary trunk in the latter.

PMID- 17202649
TI  - Pharmacokinetics of the ginkgo B following intravenous administration of ginkgo B
      emulsion in rats.
AB  - Ginkgo B (GB) is an extract from the leaves of Ginkgo biloba, used in the
      treatment of dementia, cerebral insufficiency or related cognitive decline. In
      this paper, the main features of the pharmacokinetics of GB emulsion in rats were
      reviewed and the binding rate of GB to rat plasma and human plasma protein were
      investigated meanwhile. The concentrations of GB in plasma, tissue, and excretion
      of rats after i.v. administration of GB were measured using HPLC-ESI-MS. The
      metabolite was qualitated by LC-MS/MS. Intravenously administered GB was
      eliminated in a biphasic manner with a prominent initial phase (half-life of 0.3
      h) followed by a slower terminal phase (half-life of 1.5 h). After i.v. 4, 12 and
      36 mg/kg GB emulsion, the pharmacokinetic parameters from a two compartment model
      analysis of plasma samples were AUC(0-tau) (microg x min/ml): 53.7, 165.5 and
      649.7; CL (l/min/kg): 0.07, 0.07 and 0.05; V(C) (l/kg): 2.27, 3.27 and 2.76,
      respectively. Peak concentrations generally occurred at 10 min except brain and
      fat. Tissue concentration then declined by several-fold during 6 h although still
      present in most tissues at 6 h. Single intravenous dose was mainly excreted in
      the urine (40-50%), feces contained less than 30%. The binding rate to rat plasma
      was little higher than to human plasma, but the difference was negligible. Some
      metabolites were found in urine and bile through qualitative analysis on the
      urine and bile by LC-MS/MS.

PMID- 17202650
TI  - Effect of magnesium deficiency on intracellular ATP levels in human lens
      epithelial cells.
AB  - Cataractous lenses have an altered distribution of the intracellular ionic
      environment, and the lens ionic imbalance with increased levels of calcium (Ca2+)
      and sodium (Na+), coupled with decreased levels of magnesium (Mg2+) and potassium
      (K+), is related to cataract development in human senile cataracts. We previously
      found that the decrease of ATP in lenses caused lens ionic imbalance, and
      probably decrease in ATPase function. In this study, we investigated the effect
      of Mg2+ deficiency on cataract progression using human lens epithelial (HLE)
      cells. Expression levels of inducible nitric oxide synthase (iNOS) mRNA in HLE
      cells were significantly greater in Mg2+-deficient medium (Mg2+ 0.021 mM) than in
      normal Mg2+ medium (Mg2+ 0.77 mM). The NO release from the HLE cells cultured
      with Mg2+-deficient medium also increased. On the other hand, the ATP levels in
      HLE cells 24 h after incubation with Mg2+-deficient medium were lower than that
      with normal Mg2+ medium. The Ca2+- and Na+/K+-ATPase activities in HLE cells
      until 24 h incubation with normal Mg2+ or Mg2+-deficient medium did not change.
      Both diethyldithiocarbamate 10 microM and aminoguanidine 250 microM attenuated
      the increase of NO release, and caused an increase in ATP levels in HLE cells 24
      h after incubation with Mg2+-deficient medium. These results suggest that Mg2+
      deficiency enhances NO production via iNOS in the lens. It is possible that the
      excessive production of NO cause the decrease of ATP levels. These results show
      that Mg2+ deficiency in the lens may cause an acceleration of the progression of
      lens opacification.

PMID- 17202651
TI  - Cloning, expression and purification of arylsulfate sulfotransferase from
      Eubacterium A-44.
AB  - A gene (astA) encoding arylsulfate sulfotransferase (ASST), which transfers a
      sulfate group from phenolic sulfate esters to phenolic acceptors, was cloned from
      a Eubacterium A-44 genomic library. The probe (1.5 kb fragment) for the astA gene
      was prepared from the PCR product of the primers produced using two internal
      amino acid sequences of ASST, which had been purified from Eubacterium A-44. The
      astA gene was cloned into the pKF3 vector. Its sequence revealed a 1863 bp open
      reading frame (ORF) encoding a protein containing 620 amino acids with a
      secretary signal peptide, and showed 91% homology (identity) to Eubacterium
      rectale IIIH previously reported. The cloned astA gene was expressed under the T7
      promoter of the expression vectors, pET-39b(+) and pET-26b(+), in Escherichia
      coli BL21 (DE3), and the expressed ASSTs were purified using His Bind column
      chromatography. The specific activities of the purified ASSTs were 25.6
      micromol/min/mg and 37.1 micromol/min/mg, respectively.

PMID- 17202652
TI  - Nitration of specific tyrosine residues of cytochrome C is associated with
      caspase-cascade inactivation.
AB  - Peroxynitrite, a potent oxidative stress inducer, inhibits the mitochondrial
      electron transfer, induces cell death, and is considered to be involved in the
      pathology of various diseases. However, the intracellular mechanisms involved in
      the cell death process are not fully understood. Here we demonstrate that the
      enhanced nitration of specific tyrosine residues of cytochrome c, which are
      induced by continuous peroxynitrite exposure, attenuates cytochrome c-induced
      caspase-9 activation in vitro. Interestingly, cytochrome c nitrated with a single
      high dose of peroxynitrite preserved its potency, while this did not occur when
      cytochrome c was treated with continuous peroxynitrite exposure. Although both of
      these experiments resulted in cytochrome c nitration at the tyrosine residues, it
      was found that nitration at specific residues was enhanced only when cytochrome c
      was exposed to continuous peroxynitrite. This is the first report to demonstrate
      that cytochrome c nitration affects the apoptotic pathway by means of enhancement
      of nitration at specific tyrosine residues. This result implies that the
      nitration pattern of cytochrome c may affect the efficacy of the mitochondrial
      pathway in apoptotic cell death.

PMID- 17202653
TI  - The additive effects of minoxidil and retinol on human hair growth in vitro.
AB  - Minoxidil enhances hair growth by prolonging the anagen phase and induces new
      hair growth in androgenetic alopecia (AGA), whereas retinol significantly
      improves scalp skin condition and promotes hair growth. We investigated the
      combined effects of minoxidil and retinol on human hair growth in vitro and on
      cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT).
      The combination of minoxidil and retinol additively promoted hair growth in hair
      follicle organ cultures. In addition, minoxidil plus retinol more effectively
      elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio
      than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft
      elongation demonstrated after minoxidil plus retinol treatment would depend on
      the dual kinetics associated with the activations of Erk- and Akt-dependent
      pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.

PMID- 17202654
TI  - Stimulatory effects of hydroxyl radical generation by Ga-Al-As laser irradiation
      on mineralization ability of human dental pulp cells.
AB  - The present study was conducted to investigate the effects of Ga-Al-As laser
      irradiation on the mineralization ability of human dental pulp (HDP) cells. HDP
      cells in vitro were irradiated once with a Ga-AL-As laser at 0.5 W for 500 s and
      at 1.0 W for 500 s in order to investigate free radicals as one mechanism for
      transmission of laser photochemical energy to cells. Production of the hydroxyl
      radical (*OH) was measured using the ESR spin-trapping method and was found to be
      increased by laser irradiation. The DMPO-OH was not detected in the presence of
      dimethyl sulfoxide (DMSO), a *OH scavenger. The formation of calcification nodule
      was also investigated by von Kossa staining. The number of calcified nodules was
      increased by 1.0 W-laser irradiation. Alkaline phosphatase (ALP) activity was
      higher in the 1.0 W-laser irradiation group. Expression of mRNAs for heat shock
      protein 27, bone morphogenetic proteins (BMPs) and ALP were greater in the 1.0 W
      laser irradiation group. Expression of BMPs in the conditioned medium was also
      higher in the 1.0 W-laser irradiation group. In particular, DMSO decreased the
      number of calcified nodule produced by 1.0 W-laser irradiation. These results
      supposed that the mineralization of HDP cells is stimulated by laser irradiation,
      and that *OH generated by laser irradiation is a trigger for promotion of HDP
      cell mineralization.

PMID- 17202655
TI  - The anti-apoptotic and anti-oxidant effect of eriodictyol on UV-induced apoptosis
      in keratinocytes.
AB  - Recently, considerable scientific and therapeutic interest has focused on the
      structure and functions of the flavonoids. In a previous study, we suggested that
      hydroxyl (OH) substitutions on specific carbons in the skeleton of the flavonoids
      might significantly affect their apoptosis-modulating properties. Here, to
      investigate the effect of various OH substitutions on their diphenylpropane
      (C6C3C6) skeleton carbons, we selected 10 different flavonoids and assessed their
      role on UV-induced apoptosis of human keratinocytes, the principal cell type of
      epidermis. The results showed that 5,7,3',4'-tetrahydroxylflavanone (eriodictyol)
      and 3,4'-dihydroxy flavone (3,4'-DHF) had a positive effect on cell proliferation
      of human HaCaT keratinocytes. Treatment with eriodictyol in particular resulted
      in significant suppression of cell death induced by ultraviolet (UV) light, a
      major skin-damaging agent. We found that eriodictyol treatment apparently reduced
      the percentage of apoptotic cells and the cleavage of poly(ADP-ribose)
      polymerase, concomitant with the repression of caspase-3 activation and reactive
      oxygen species (ROS) generation. The anti-apoptotic and anti-oxidant effects of
      eriodictyol were also confirmed in UV-induced cell death of normal human
      epidermal keratinocyte (NHEK) cells. Taken together, these findings suggest that
      eriodictyol can be used to protect keratinocytes from UV-induced damage, implying
      the presence of a complex structure-activity relationship (SAR) in the
      differential apoptosis-modulating activities of various flavonoids.

PMID- 17202656
TI  - Effects of Anemarrhena asphodeloides on focal ischemic brain injury induced by
      middle cerebral artery occlusion in rats.
AB  - The preventive effect of Anemarrhena asphodeloides Bunge (Liliaceae), a
      traditional Chinese medicine, on ischemia-reperfusion-induced brain injury was
      evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the
      right middle cerebral artery for 2 h and reperfusion was continued for 22 h.
      Water extract of Anemarrhena asphodeloides (WEAA) was orally administered
      promptly prior to and 2 h after reperfusion. Total infarct volume and edema in
      the ipsilateral hemispheres of ischemia-reperfusion rats were significantly
      reduced by treatment with WEAA in a dose-dependent manner (p<0.05). The
      therapeutic time window of WEAA was 3 h in this ischemia-reperfusion rat model.
      WEAA also significantly inhibited increased neutrophil infiltration of ischemic
      brain tissue as estimated by myeloperoxidase (MPO) activity and
      immunohistochemical analysis. MPO-positive cells were markedly reduced by WEAA
      administration in striatal and cortical areas. These findings suggest that WEAA
      plays a crucial protective role in ischemia-induced brain injury, and suggest
      that WEAA could serve as a lead medicinal herb for the development of
      neuroprotective agents following transient focal ischemic brain injury.

PMID- 17202658
TI  - Endothelium-dependent vasodilatory and hypotensive effects of Crotalaria
      sessiliflora L. in rats.
AB  - The aim of the present study was to investigate the vasoactive effect of
      Crotalaria sessiliflora L. extract (CSE) on rats and its mechanism when combining
      in vivo and in vitro approaches. CSE (0.5-5 mg/ml) induced concentration
      dependent relaxation on endothelium-intact thoracic aortic rings precontracted
      with phenylephrine (PE, 10(-5) M). This effect disappeared with the removal of
      functional endothelium. Pretreatment of the aortic strips with either N(G)-nitro
      L-arginine (L-NNA, 10(-5) M) or methylene blue (10(-5) M) significantly reduced
      the relaxation induced by CSE. The endothelium-dependent relaxation caused by CSE
      was associated with production of cGMP. CSE (5 mg/ml) increased the production of
      cGMP in endothelium-intact aortic rings and this effect was significantly
      attenuated by L-NNA (10(-5) M) and methylene blue (10(-5) M). Relaxation in
      response to CSE in strips precontracted with PGF2alpha (3x10(-5) M) was
      eliminated by removing extracellular Ca2+ and significantly reduced by
      pretreatment with ruthenium red (10(-5) M). In in vivo tests, injection of 40
      mg/kg of CSE induced an increase in plasma NO production, and this effect was
      blocked by L-NNA. Furthermore, CSE produced dose-dependent and transient decrease
      in blood pressure in normotensive rats and this effect was blocked by atropine as
      well as L-NNA. These findings suggest that CSE induces endothelium-dependent
      relaxation via NO/cGMP signaling by promoting extracellular Ca2+ influx and the
      release of Ca2+ from intracellular stores of endothelium, probably due to
      endothelial muscarinic receptor activation.

PMID- 17202657
TI  - Protective effect of salvianic acid a on acute liver injury induced by carbon
      tetrachloride in rats.
AB  - Previous research has shown that salvianic acid A [2-(3,4-dihydroxyphenyl)-2
      hydroxy-propanoic acid, SA] extracted from Salvia miltiorrhiza BGE (Danshen)
      markedly inhibits lipid peroxidation of mitochondrial membrane of hepatic cells
      in vitro. The present study was conducted to examine protective effect of SA on
      liver injury induced by carbon tetrachloride (CCl4) and its possible mechanism in
      vivo. Male Sprague-Dawley rats weighing 180-200 g were used in the experiments.
      Five mmol/kg CCl4 in olive oil was given to rats i.p. Spectrophotometrical method
      was used to measure activities of aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) in serum, activities of superoxide dismutase (SOD),
      catalase (CAT), and glutathione peroxidase (GPx) as well as malondialdehyde (MDA)
      level in hepatic tissue and the rate of superoxide anion (O2*-) generation in
      hepatic submitochondrial particles. Hepatic histological structure was observed
      under light microscopy. CCl4 caused significant changes of activities of the
      enzymes, MDA level, and the rate of O2*- generation and histopathological changes
      of acute hepatic injury were noted. SA reversed the significant changes induced
      by CCl4. These results demonstrate that SA produces protective action on acute
      hepatic injury induced by CCl4 via an antioxidative mechanism.

PMID- 17202659
TI  - Pharmacological characterization of a new antimuscarinic agent, solifenacin
      succinate, in comparison with other antimuscarinic agents.
AB  - Solifenacin succinate [YM905; (3R)-1-azabicyclo[2.2.2]oct-3-yl(1S)-1-phenyl-3,4
      dihydroisoquinoline-2(1H)-carboxylate monosuccinate] is a new muscarinic receptor
      antagonist developed for the treatment of overactive bladder. The aim of the
      present study was to evaluate the antimuscarinic properties of solifenacin and to
      compare the results with those obtained for tolterodine, oxybutynin, darifenacin,
      propiverine and atropine. In radioligand receptor binding assay, Ki values of
      solifenacin for human muscarinic M1, M2, M3, M4 and M5 receptors were 26, 170,
      12, 110 and 31 nM, respectively. In isolated rat urinary bladder, solifenacin
      competitively antagonized carbachol-induced contractions, with a pA2 value of
      7.44+/-0.09. In these in vitro studies, the antimuscarinic action of solifenacin
      was more potent than that of propiverine and less potent than those of
      tolterodine, oxybutynin, darifenacin and atropine. In anesthetized rats,
      solifenacin and oxybutynin increased the maximum bladder capacity in a dose
      dependent manner and also decreased the maximum intravesical pressure. The
      dosages required to produce a 30% increase in maximum bladder capacity (ED30
      values) of solifenacin and oxybutynin were 0.35 and 0.30 mg/kg i.v.,
      respectively, indicating approximately equal efficacies. These results support
      the fact that solifenacin, similarly to currently used antimuscarinic agents, is
      an effective agent in the treatment of overactive bladder symptoms such as
      urinary frequency and urge incontinence.

PMID- 17202660
TI  - Tetrandrine inhibits proinflammatory cytokines, iNOS and COX-2 expression in
      human monocytic cells.
AB  - Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the dried root
      of hang-fang-chi (Stephania tetrandra S. Moore), is traditionally used in China
      for treating inflammation, hypertension and silicosis. In this study, our aim was
      to examine the anti-inflammatory mechanism of TET through measuring the inducible
      nitric oxide synthase (iNOS), cyclooxygenase-1, and -2 (COX-1 and COX-2)
      expression, cytokines (TNF-alpha, IL-4 and IL-8) formation, nitric oxide (NO)
      release and prostaglandin E2 (PGE2) generation in lipopolysaccharide (LPS)
      induced human monocytic (THP-1) cells. Results showed that TET remarkably
      suppressed the LPS (1 microg/ml) induction of NO release and PGE2 generation. It
      also significantly attenuated the LPS-induced transcription of proinflammatory
      cytokines (TNF-alpha, IL-4 and IL-8) in a dose-dependent manner. Furthermore, TET
      at 100 microM significantly blocked the LPS induction of iNOS and COX-2
      expression, but not the COX-1. Taken together, these results suggest that TET
      exerts anti-inflammatory effects probably through the suppression of COX-2 and
      iNOS expression.

PMID- 17202661
TI  - Anti-inflammatory activity of bis(3-aryl-3-oxo-propyl)methylamine hydrochloride
      in rat.
AB  - In this study the effects of compound B1, bis(3-aryl-3-oxo-propyl)methylamine
      hydrochloride, and an anti-inflammatory drug, indomethacin, were tested by
      carrageenan-induced paw edema and cotton pellet granuloma tests, for effects on
      acute and chronic phases of inflammation, respectively. Their effects on vascular
      permeability were also determined by hyaluronidase-induced capillary permeability
      test. Anti-inflammatory activity of B1 was compared with indomethacin. B1
      decreased the carrageenan-induced paw edema by 49%, 35%, and 47% at 50, 100, and
      200 mg kg(-1) doses, respectively, while this decrease was 82% by indomethacin at
      20 mg kg(-1) dose. Antiproliferative effects in cotton pellet test of B1 at 50 mg
      kg(-1) and indomethacin at 20 mg kg(-1) doses were 44% and 43%, respectively.
      Indomethacin but not B1 inhibited the hyaluronidase-induced increase in capillary
      permeability. Our results suggest that B1 inhibits both acute and chronic phases
      of inflammation probably by an effect not mediated by prevention of increased
      capillary permeability. Especially, its anti-inflammatory activity against
      chronic phase of inflammation was comparable with that of indomethacin. Further
      detailed studies are needed to clarify the mechanism(s) of action responsible for
      the anti-inflammatory activity of B1.

PMID- 17202662
TI  - Fcr1p inhibits development of fluconazole resistance in Candida albicans by
      abolishing CDR1 induction.
AB  - Overexpression of Candida drug resistance 1 (CDR1) gene in Candida albicans (C.
      albicans), an efflux pump, is one of the major mechanisms contributing to drug
      resistance. C. albicans for fluconazole resistance 1 protein (Fcr1p) is a member
      of the family of zinc cluster proteins homologous to Pdr1p and Pdr3p (pleiotropic
      drug resistance protein) mediating azole resistance in Saccharomyces cerevisiae
      (S. cerevisiae) by regulating the expression of pleiotropic drug resistance 5
      (PDR5) homologous to C. albicans CDR1. A previous study has showed that for
      fluconazole resistance 1 (FCR1) could also confer azole resistance in S.
      cerevisiae pdr1 pdr3 mutant by regulating PDR5. Therefore, we investigated the
      role of FCR1 in the development of C. albicans azole resistance in vitro and in
      vivo. Our results showed that Fcr1p inhibited fluconazole (FLC) resistance
      development in C. albicans through abolishing the induction of CDR1 expression by
      FLC, and in contrast FLC resistance development was accelerated resulting from
      the deletion of FCR1.

PMID- 17202663
TI  - Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated
      derivatives.
AB  - The antioxidant activities of curcumin, its natural demethoxy derivatives
      (demethoxycurcumin, Dmc and bisdemethoxycurcumin, Bdmc) and metabolite
      hydrogenated derivatives (tetrahydrocurcumin, THC; hexahydrocurcumin, HHC;
      octahydrocurcumin; OHC) were comparatively studied using 2,2-diphenyl-1
      picrylhydrazyl (DDPH) radical, 2,2'-azobis(2-amidinopropane)dihydrochloride
      (AAPH) induced linoleic oxidation and AAPH induced red blood cell hemolysis
      assays. Hydrogenated derivatives of curcumin exhibited stronger DPPH scavenging
      activity compared to curcumin and a reference antioxidant, trolox. The scavenging
      activity significantly decreased in the order
      THC>HHC=OHC>trolox>curcumin>Dmc>>>Bdmc. Stronger antioxidant activities toward
      lipid peroxidation and red blood cell hemolysis were also demonstrated in the
      hydrogenated derivatives. By the model of AAPH induced linoleic oxidation, the
      stoichiometric number of peroxyl radical that can be trapped per molecule (n) of
      hydrogenated derivatives were 3.4, 3.8 and 3.1 for THC, HHC and OHC,
      respectively. The number (n) of curcumin and Dmc were 2.7 and 2.0, respectively,
      which are comparable to trolox, while it was 1.4 for Bdmc. The inhibition of AAPH
      induced red blood cell hemolysis significantly decreased in the order
      OHC>THC=HHC>trolox>curcumin=Dmc. Results in all models demonstrated the lower
      antioxidant activity of the demethoxy derivatives, suggesting the ortho
      methoxyphenolic groups of curcumin are involved in antioxidant activities. On the
      other hand, hydrogenation at conjugated double bonds of the central seven carbon
      chain and beta diketone of curcumin to THC, HHC and OHC remarkably enhance
      antioxidant activity.

PMID- 17202664
TI  - Gentamicin-induced nephrotoxicity in rats ameliorated and healing effects of
      resveratrol.
AB  - In this study, we aimed to investigate the possible protective effect of
      resveratrol on gentamicin induced nephrotoxicity. Experiments were carried out in
      male Wistar rats weighing 200-250 g. Gentamicin sulfate (80 mg/kg per day i.p.),
      resveratrol (10 mg/kg per day i.p.) and gentamicin together with resveratrol were
      administered for 6 d. The animals were sacrificed 24 h after the last injection.
      Urine, blood samples and tissue samples were collected from the animals on the
      seventh day of the treatment before they were sacrificed. Kidneys were collected
      for histopathological studies and fixed in 10% buffered formalin solution. Tissue
      samples were stored at -70 degrees C in liquid nitrogen for the determination of
      glutathione (GSH), glutathione-S-transferase (GST), malondialdehyde (MDA) and
      catalase (CAT). Glutathione assay was determined by the method of Beutler et al.
      GST amounts were measured by the method of Habig et al. Catalase activity was
      tested by Aebi's method and MDA was determined according to Thayer's method.
      Blood urea level was significantly increased in the gentamicin treated group. The
      study showed lowered levels of urea and creatinine levels in resveratrol
      administered groups when compared with gentamicin administered rats, and the
      difference was statistically significant. It has been determined that resveratrol
      caused statistically significant decrease in lipid peroxidation and reduced the
      level of catalase. Histopathological examination showed that resveratrol
      prevented partly gentamicin induced tubular damage. The results
      histopathologically demonstrated that resveratrol has a protective effect against
      gentamicin induced nephrotoxicity, lipid peroxidation and cellular damage in
      rats.

PMID- 17202666
TI  - A novel vasopressin dual V1A/V2 receptor antagonist, conivaptan hydrochloride,
      improves hyponatremia in rats with syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH).
AB  - We investigated the effects of intravenous administration of conivaptan
      hydrochloride, a dual vasopressin V1A and V2 receptor antagonist, on blood
      electrolytes and plasma osmolality in rats with an experimental syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH). The experimental SIADH
      rat model was developed by means of continuous administration of arginine
      vasopressin (AVP) via a subcutaneously implanted osmotic mini pump, and
      hyponatremia was induced by additional water loading. This model possesses
      similar characteristics to those observed in patients with SIADH, specifically
      decreases in blood sodium concentration and plasma osmolality. In this
      experimental model, intravenous administration of conivaptan (0.1, 1 mg/kg)
      significantly increased blood sodium concentration and plasma osmolality. On the
      other hand, intravenous administration of furosemide (10 mg/kg) did not increase
      either blood sodium concentration or plasma osmolality in the SIADH rats.
      Moreover, furosemide significantly lowered blood potassium concentration. These
      results show that conivaptan improves hyponatremia in rats with SIADH, supporting
      the therapeutic potential of conivaptan in treatment of patients with
      hyponatremia associated with SIADH.

PMID- 17202665
TI  - Protection of testicular dysfunctions by MTEC, a formulated herbal drug, in
      streptozotocin induced diabetic rat.
AB  - Single injection of streptozotocin (STZ) resulted diabetes mellitus which was
      reflected here by the levels of fasting blood glucose and serum insulin.
      Moreover, this experimental diabetes also resulted testicular dysfunctions
      evaluated by count, viability and motility of sperm as well as by the activities
      of key enzymes for androgen synthesis. Diabetes induced testicular oxidative
      stress has been indicated here by the monitoring of testicular peroxidase and
      catalase activities as well as by quantification of TBARS and CD of testis.
      Testicular glucose was increased and leydig cell nuclear area was decreased in
      STZ induced diabetes. Treatment of herbal formulated drug named as MTEC consist
      of aqueous-methanol extract of Musa paradisiaca, Tamarindus indica, Eugenia
      jambolana and Coccinia indica to streptozotocin induced diabetic rat at the ratio
      of 2:2:1:1 at the dose of 60 mg/d for two times a day for 14 d resulted a
      significant protection in fasting blood glucose and serum insulin levels (p<0.05)
      along with correction of testicular above parameters towards the control level
      (p<0.05). This herbal formulated drug has no general toxic effects on the body
      weight, as well as on the activities of serum glutamate and pyruvate
      transaminases in serum. The results support the validity of this herbal drug for
      the management of testicular disorders noted in diabetic state.

PMID- 17202667
TI  - Cardiovascular effects of an n-butanol extract from fresh fruits of Randia
      siamensis.
AB  - Randia siamensis is used in Thai folklore medicine for inducing abortion and
      controlling blood pressure. The present study investigated the cardiovascular
      effects of an R. siamensis fruit extract, and mechanisms involved in anesthetized
      normal and reserpinized rats. R. siamensis (0.4-12 mg/kg) i.v. increased the mean
      arterial pressure (MAP) and heart rate. Both effects were significantly inhibited
      by phentolamine (2 mg/kg, i.v.) or propranolol (0.6 mg/kg, i.v.). The combination
      of phentolamine and propranolol, or reserpine pretreatment, inhibited the
      positive chronotropic effect with a slight decrease in the MAP. In vitro, R.
      siamensis (0.001-0.3 mg/ml) increased the rate of beating of the right atrium and
      the strength of the electrical field-stimulated contraction of the left atrium,
      both effects were inhibited by propranolol, or with reserpine pretreated rats. R.
      siamensis (0.01-3 mg/ml) produced a contraction of isolated thoracic aorta, which
      was potentiated by N(G)-nitro-L-arginine (LNA), or by removal of the vascular
      endothelium, but inhibited by phentolamine, or reserpine. R. siamensis (0.3-3
      mg/ml) caused a relaxation of phenylephrine-preconstricted aortic rings, which
      was potentiated with reserpine pretreatment, and abolished after removal of the
      vascular endothelium, or in the presence of LNA. These results suggest that R.
      siamensis extract exerts both hypertensive and positive chronotropic effects via
      the alpha- and beta-adrenergic receptors of blood vessels and the heart, due to
      release of endogenous catecholamines, likely from nerve ending and adrenal
      medulla. The hypotensive activity results from the release of nitric oxide
      causing dilatation of the blood vessels. The present data support the folklore
      therapeutic uses of this plant.

PMID- 17202668
TI  - Changes in Hsp60 level of the failing heart following acute myocardial infarction
      and the effect of long-term treatment with trandolapril.
AB  - Changes in heat shock protein (Hsp) 60 of the viable left ventricular muscle
      (viable LV) after myocardial infarction in rats and the effect of the angiotensin
      I-converting enzyme inhibitor (ACEI) trandolapril were examined. Myocardial
      infarction was induced in rats by ligation of the left coronary artery. The
      coronary artery-ligated (CAL) and sham-operated (Sham) rats were orally treated
      with 3 mg/kg/d trandolapril from the 2nd to 8th week after surgery. Hemodynamic
      parameters and tissue weights of the left and right ventricles of the animals at
      the 8th week after CAL (8w-CAL rats) showed signs indicating chronic heart
      failure. An increase in Hsp60 content, a decrease in mitochondrial oxygen
      consumption rate (OCR), and an increase in the mitochondrial thiobarbiturate
      reacting substance (TRS) of the viable LV were detected. Eight weeks after CAL.
      Long-term treatment of the CAL rats with trandolapril improved the hemodynamic
      parameters, attenuated the CAL-induced increase in Hsp60 content, the decrease in
      mitochondrial OCR, and the increase in the mitochondrial TRS content of the
      viable LV at the 8th week after myocardial infarction. The increase in Hsp60
      content was closely related to the decrease in the mitochondrial OCR and to a
      rise in the LVEDP of the CAL animal at the 8th week after myocardial infarction.
      These results suggest that a series of pathophysiological alterations, including
      a reduction in mitochondrial function, appearance of reactive oxygen stress, and
      production of Hsp60 is involved in the development of cardiac failure and that
      trandolapril is beneficial for preventing these alterations.

PMID- 17202669
TI  - Glycoprotein isolated from Rhus verniciflua Stokes inhibits inflammation-related
      protein and nitric oxide production in LPS-stimulated RAW 264.7 cells.
AB  - Rhus verniciflua Stokes (RVS) has traditionally been used for medical purpose,
      such as healing of inflammatory diseases in South Korea. Glycoprotein (36 kDa)
      was isolated from RVS fruit, purified and used to evaluate the inhibitory effect
      on inflammatory-related proteins and nitric oxide (NO) production in
      lipopolysaccharide (LPS, 200 ng/ml)-stimulated RAW 264.7 (murine macrophage cell
      line). Our results were showed that RVS glycoprotein has a strong antioxidative
      activity against lipid peroxyl radicals in cell-free system, and inhibits NO
      production in LPS-stimulated RAW 264.7 cells. To elucidate the inhibitory effect
      of RVS glycoprotein on activities of inflammatory-related proteins, we firstly
      evaluated the amount of intracellular reactive oxygen species (ROS), and
      expression of intracellular protein kinase C (PKC), nuclear factor (NF)-kappaB,
      and activator protein-1 (AP-1). The results in the present study showed that RVS
      glycoprotein (200 microg/ml) inhibits ROS production and PKCalpha translocation,
      and down-regulates the expression of NF-kappaB and AP-1. Such upstream signals
      consequently inhibited the levels of inducible NO synthase (iNOS) and
      cyclooxygenase (COX)-2 expression. Therefore, we speculate that RVS glycoprotein
      inhibits the inflammatory-related protein and can act as an anti-inflammatory
      agent.

PMID- 17202671
TI  - Potent inhibition of serum-stimulated responses in vascular smooth muscle cell
      proliferation by 2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone, a newly
      synthesized 1,4-naphthoquinone derivative.
AB  - Atherosclerosis, a disease of the large arteries, is the primary cause of heart
      disease and stroke. The abnormal proliferation of vascular smooth muscle cells
      (VSMCs) in arterial walls is an important pathogenetic factor of vascular
      disorders like atherosclerosis and restenosis after angioplasty. In the present
      study, the possible anti-proliferative effect of a synthetic 1,4-naphthoquinone
      derivative, 2-chloro-3-(4-hexylphenyl)-amino-1,4-naphthoquinone (NQ304) was
      investigated on rat aortic VSMCs. NQ304 was shown to potently inhibit 5% fetal
      bovine serum (FBS)-induced the growth of VSMCs. Pre-treatment of VSMCs with NQ304
      (1-10 microM) for 24 h resulted in significant cell number decreases, i.e.,
      inhibition percentages were 44.75+/-10.77, 73.85+/-6.38 and 89.77+/-6.52% at
      NQ304 concentrations of 1, 5 and 10 microM, respectively. NQ304 was also found to
      significantly inhibit 5% FBS-induced DNA synthesis in a concentration-dependent
      manner. Furthermore, NQ304 elevated p21(cip1) and p27(kip1) mRNA levels and
      caused G0/G1 phase arrest in cell cycle progression. However, no evidence of
      NQ304-induced apoptotic or necrotic cell death was obtained, as determined by
      flow cytometry analysis and DNA fragmentation assays. To investigate the
      mechanism underlying the anti-proliferative effect of NQ304, we examined the
      effects of NQ304 on c-fos mRNA expression, activator protein-1 (AP-1) binding
      activity and extracellular signal-regulated kinase1/2 (ERK1/2) and Akt
      activation. Pre-treatment of VSMCs with NQ304 (1-10 microM) was found to
      significantly inhibit the 5% FBS-induced phosphorylations of ERK1/2 and Akt, the
      activation of AP-1 and the expression of c-fos. These data suggest that the anti
      proliferative and cell cycle arresting effects of NQ304 on serum-induced VSMCs
      may be mediated by AP-1 activation downregulation via the suppression of
      phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2 signaling pathways, and it
      may contribute to the prevention of atherosclerosis through inhibition of VSMC
      proliferation.

PMID- 17202670
TI  - The 5-HT1A receptor full agonist, 8-OH-DPAT inhibits ACTH-induced 5-HT2A receptor
      hyperfunction in rats: involvement of 5-HT1A receptors in the DOI-induced wet-dog
      shakes in ACTH-treated rats.
AB  - We examined the influence of 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT), a
      serotonin 1A (5-HT1A) receptor full agonist, on the wet-dog shake response
      induced by the (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5
      HT2A receptor agonist, in adrenocorticotropic hormone (ACTH)-treated rats.
      Chronic ACTH (100 microg/rat, s.c.) treatment for 14 d increased the wet-dog
      shake response induced DOI. The 8-OH-DPAT inhibited the wet-dog shake response
      induced by DOI in rats with ACTH for 14 d. On the other hand, the 8-OH-DPAT
      induced hypothermia and flat body posture were inhibited when ACTH was
      administered for 14 d. These findings suggest that chronic treatment with ACTH
      decreased the sensitivity of the 5-HT1A receptor system; however, the inhibitory
      effects from the 5-HT1A receptors to the 5-HT2A receptor system is not inhibited
      in ACTH-treated rats.

PMID- 17202672
TI  - Mitochondria-dependent apoptosis induced by nanoscale hydroxyapatite in human
      gastric cancer SGC-7901 cells.
AB  - Nanoscale hydroxyapatite (nano-HAP) has been reported to exhibit anti-cancer
      effect on several human cancers, but the molecular mechanism of which remains
      unclear. The aim of this study was to explore the mechanisms by investigating the
      effects of nano-HAP on human gastric cancer SGC-7901 cells. Our results showed
      that nano-HAP significantly reduced cell viability, and induced apoptosis in SGC
      7901 cells characterized by hypodiploid DNA contents, morphological changes and
      DNA fragmentation. The increase in apoptosis was accompanied with the increased
      expression of Bax, a pro-apoptotic protein, and decreased expression of Bcl-2, an
      anti-apoptotic protein, the decrease of mitochondrial membrane potential and the
      release of cytochrome c from mitochondria into cytosol. Furthermore, the
      activation of caspases-3, and -9, but not activation of caspases-8 was induced by
      nano-HAP. Z-VAD-fmk, a universal caspase inhibitor, dose-dependently inhibited
      nano-HAP-induced apoptosis. This study demonstrates that nano-HAP inhibits the
      proliferation of SGC-7901 cells by inducing apoptosis, and the apoptotic pathway
      of nano-HAP-induced apoptosis is mediated through the mitochondrial-dependent and
      caspase-dependent pathway.

PMID- 17202673
TI  - Overproduction of N(epsilon)-(carboxymethyl)lysine-induced neovascularization in
      cultured choroidal explant of aged rat.
AB  - N(epsilon)-(carboxymethyl)lysine (CML) adduct, a major structure of advanced
      glycation end product, facilitated production of immature microvessels from
      choroidal explant cultured in fibrin gel. The present study was investigated an
      action of endogenous CML adduct on neovascularization of cultured choroidal
      explants of aged Wistar rats with 9 months of age. The number of microvessels
      budded from explants was counted under optical microscope and used as an index of
      in vitro neovascularization. Aged choroidal explants increased the
      neovascularization in an age-dependent manner. Anti-CML antibody decreased age
      facilitated neovascularization as well as CML-human serum albumin (HSA)
      facilitated neovascularization. Both the aged explant and CML-HSA-treated explant
      significantly released vascular endothelial growth factor (VEGF), tumor necrosis
      factor (TNF) alpha and platelet-derived growth factor (PDGF)-B during the culture
      period. The release of TNF alpha and PDGF-B was earlier than that of VEGF from
      the aged explants. The antibodies against these factors decreased the CML
      facilitated and age-facilitated neovascularization in the choroidal explants. The
      inhibitory capacity of anti-TNF alpha antibody was greater than those of anti
      VEGF and anti-PDGF-B antibodies. In conclusion, endogenous CML adduct
      overproduced the neovascularization of the aged choroidal explant. The CML adduct
      releases TNF alpha which might induce the production and release of VEGF for the
      abnormal choroidal neovascularization in the patients of age-related macular
      degeneration.

PMID- 17202674
TI  - Styraxoside A isolated from the stem bark of Styrax japonica inhibits
      lipopolysaccharide-induced expression of inducible nitric oxide synthase and
      cyclooxygenase-2 in RAW 264.7 cells by suppressing nuclear factor-kappa B
      activation.
AB  - In the present study, the effects of terpenes (styraxosides A and B) and lignans
      (egonol, masutakeside I, and styraxlignolide A) isolated from the stem bark of
      Styrax japonica Sieb. et Zucc. (styracaceae) were evaluated on lipopolysaccharide
      (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by the RAW
      264.7 macrophage cell line. Of the tested compounds, styraxoside A was found to
      most potently inhibit the productions of NO and PGE2, and also significantly
      reduced the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta). Consistent with these observations, the protein expression
      levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and
      the mRNA expression levels of iNOS, COX-2, TNF-alpha and IL-1beta were found to
      be inhibited by styraxoside A in a concentration-dependent manner. Furthermore,
      styraxoside A inhibited the LPS-induced DNA binding activity of nuclear factor
      kappaB (NF-kappaB). Taken together, our data indicate that styraxoside A inhibits
      LPS-induced iNOS, COX-2, TNF-alpha, and IL-1beta expressions through the down
      regulation of NF-kappaB-DNA binding activity.

PMID- 17202675
TI  - Isoliquiritigenin, one of the antispasmodic principles of Glycyrrhiza ularensis
      roots, acts in the lower part of intestine.
AB  - Glycyrrhizae radix is used to treat abdominal pain as a component of
      shakuyakukanzoto (shaoyao-gancao-tang), a traditional Chinese medicine
      formulation. Previously, we have reported the isolation of glycycoumarin as a
      potent antispasmodic with an IC50 value of 2.93+/-0.94 microM for carbamylcholine
      (CCh)-induced contraction of mouse jejunum from an aqueous extract of
      Glycyrrhizae radix (licorice), and clarified that its mechanism of action
      involves inhibition of phosphodiesterase 3. The purpose of the present study was
      to examine an antispasmodic principle of licorice other than glycycoumarin.
      Isoliquiritigenin was isolated from an aqueous extract of licorice as a potent
      relaxant, which inhibited the contraction induced by various types of stimulants,
      such as CCh, KCl, and BaCl2 with IC50 values of 4.96+/-1.97 microM, 4.03+/-1.34
      microM and 3.70+/-0.58 microM, respectively, which are close to those of
      papaverine. However, the amount of isoliquiritigenin in the aqueous extract of
      licorice was very small. When the aqueous licorice extract was treated with
      naringinase, the amounts of glycosides such as isoliquiritin, which were abundant
      but had much less potent relaxant activity, were decreased while
      isoliquiritigenin was increased. At the time, the relaxant activity of the
      treated sample was increased significantly, shifting the IC50 from 358+/-104 to
      150+/-38 microg/ml for CCh-induced contraction. Isoliquiritigenin also showed the
      most potent inhibition of mouse rectal contraction induced by CCh with an IC50
      value of 1.70+/-0.07 microM. These results suggest that isoliquiritigenin acts as
      a potent relaxant in the lower part of the intestine by transformation from its
      glycosides.

PMID- 17202677
TI  - Pharmacokinetics/pharmacodynamics of acetaminophen analgesia in Japanese patients
      with chronic pain.
AB  - Acetaminophen (APAP) is a popular analgesic. In the present study, we
      characterized the pharmacokinetics and pharmacodynamics of APAP in the Japanese.
      Five healthy volunteers were administered 1000 mg of APAP orally. Five patients
      with chronic pain were administered the optimal oral dose of APAP ranging from
      600 to 1000 mg to allow for an adequate analgesic effect. Plasma APAP and APAP
      metabolite concentrations were measured in the volunteers, plasma APAP
      concentrations and pain scores using a visual analog scale were measured in the
      patients with chronic pain. Patient data were fitted to a first-order absorption
      one-compartment model with delayed effects accounted for by an effect
      compartment. A sigmoid Emax model was used as the pharmacodynamic model.
      Acetaminophen-cysteine metabolites, which are conjugates of the toxic metabolite
      N-acetyl-p-benzoquinone-imine, were detected in the plasma at levels lower than
      0.2 microg/ml, but no side effects were observed. The pharmacokinetic and
      pharmacodynamic parameter (mean+/-S.D.) estimates were as follows: clearance,
      18.7+/-4.7 l/h; distribution volume, 30.9+/-6.8 l; absorption rate constant,
      2.4+/-1.3 h(-1); rate constant for the elimination of APAP from the effect
      compartment, 1.3+/-0.5 h(-1); maximum pain relief score, 4.6+/-2.2 units; effect
      compartment concentration at 50% maximum, 2.0+/-1.2 microg/ml; and sigmoid
      factor, 1.3+/-0.7. These results suggest that these parameters can be used to
      determine an effective APAP dosage regimen for Japanese patients with chronic
      pain.

PMID- 17202676
TI  - Immunological protection against HPV16 E7-expressing human esophageal cancer cell
      challenge by a novel HPV16-E6/E7 fusion protein based-vaccine in a Hu-PBL-SCID
      mouse model.
AB  - Increasing evidence has suggested that infection with high-risk human
      papillomavirus (HPVs) is closely associated with esophageal squamous cell
      carcinoma (ESCC) in China. The E6 and E7 oncoproteins expressed in ESCC are
      considered as attractive tumor-specific antigen targets for immunotherapy. We
      have reported that the HPV16 mE6delta/mE7/TBhsp70delta fusion protein vaccination
      induced powerful anti-tumor immunity against TC-1 tumor cells in a C57BL/6 mouse
      model. In the present study, we further evaluate the protective efficacy of this
      fusion protein vaccine using an HPV E7-expressing human ESCC cell line (EC9706)
      and a Hu-PBL-SCID mouse model. We demonstrated that immunization with the fusion
      protein vaccine caused significant inhibition of tumor growth with the delay time
      to tumor detection (tests vs. controls, 16 d vs. 9 d, p<0.01) and much smaller
      tumor size (p<0.01) in vivo. The inhibitory rate was ca. 69.6%, and 25% of the
      fusion protein vaccinated-mice remained tumor free by the end of the experiment
      (42 d). Furthermore, the activated lymphocytes (CD8+) were capable of
      infiltrating into the tumor site, and much more apoptotic cells along with
      activation of caspase-3 were observed in the tumors from vaccinated-mice. Also,
      high expression levels of human IFN-gamma, TNF-alpha, granzyme B and perforin
      were detected in the tumors from vaccinated-mice. Therefore, we concluded that
      the HPV16 mE6delta/mE7/TBhsp70delta fusion protein vaccine is able to stimulate
      cellular-mediated immune response against E7-containing ESCC cells through CD8+
      dependent CTL-induced apoptosis in Hu-PBL-SCID mice. These findings provide a
      scientific basis for HPV E7-expressing ESCC active immunotherapy.

PMID- 17202678
TI  - Analysis of relationship between peak inspiratory flow rate and amount of drug
      delivered to lungs following inhalation of fluticasone propionate with a
      Diskhaler.
AB  - A Diskhaler is a dry powder type of inhaler that utilizes a breath controlled
      drug delivery system. The inspiratory flow rate of the patient would have a
      significant influence on the effects of drugs administered by a Diskhaler. Thus,
      we investigated the relationship between inspiratory flow rate and amount of drug
      delivered into the lungs when using a fluticasone propionate dry powder inhaler
      with a Diskhaler (FP-DH). To investigate the amount of drug inhaled, we used an
      inhalation simulator, which consisted of a flow recorder placed in a plastic air
      tight box that covered the FP-DH equipped with a twin impinger and a vacuum pump.
      Drugs located in a plastic box, as well as the device, throat, and stage 1 and
      stage 2, were assayed by HPLC-UV, following in vitro inhalation at the various
      flow rates ranged from 18.7 to 77.3 l/min for 2 s. The relationship between peak
      inspiratory flow rate and amount of drug released from the device was analyzed. A
      positive linear correlation between the dose released from the device and amount
      of drug deposited in stage 2 was observed (r=0.899, p<0.001). The doses deposited
      in stage 2 were estimated to be 2.9 microg at a flow rate of 20 l/min, 6.6 microg
      at 30 l/min, 8.4 microg at 40 l/min, 10.1 microg at 60 l/min, and 11.3 microg at
      90 l/min. It was suggested that the amount of drug in the lungs decreased along
      with a decrease in peak inspiratory flow rate when it was lower than 60 l/min.
      Our results were found to be very useful to estimate lung deposition by using
      peak inspiratory flow rate for administration planning, especially in patients
      with a flow rate of less than 60 l/min.

PMID- 17202679
TI  - Clematis huchouensis Tamura: a traditional Chinese herbal medicine and its
      quality control using a high performance liquid chromatography technique.
AB  - A simple, specific and reliable high performance liquid chromatography (HPLC)
      method has been developed and validated for study of fingerprint chromatograms of
      extracts from the whole plant of Clematis huchouensis Tamura (CHT) for quality
      control of a traditional Chinese medicinal (TCM) herb. An Agilent C18 column was
      used to separate extracts in this protocol and detection was made by ultraviolet
      absorbance at 340 nm. The column temperature was maintained at 25 degrees C. A
      mobile phase consisting of (a) water (with 30 mM KH2PO4) and (b) CH3CN, (c) CH3OH
      was found to be suitable for this separation at a flow rate of 0.8 microl min(-1)
      with gradient elution. Under the described conditions, a fingerprint profile of 8
      compounds was collected within 35 min, which made the HPLC method unique and
      interesting. The fingerprint chromatograms had good stability, precision and
      reproducibility. Moreover, eco-climatic (habitat) effects were studied by
      comparison of fingerprint chromatograms obtained from extracts of CHT collected
      from two habitats, with rutin as a reference marker peak. The protocol developed
      is quite suitable for differentiation of extracts of CHT and can be used as a
      quality control method for this herb and a model for other herbal drugs.

PMID- 17202680
TI  - Characterization of biosurfactant-containing liposomes and their efficiency for
      gene transfection.
AB  - Recently we showed significance of biosurfactants in the field of non-viral
      vectors for gene transfection. There, a biosurfactant, mannosylerythritol lipid A
      (MEL-A), especially increased the efficiency of gene transfection mediated with
      cationic liposomes. However, the molecular mechanism has not been well-understood
      yet. Here, through the examination of the ability of cationic liposomes
      containing an MEL (MEL-A, MEL-B or MEL-C) for important transfectional processes
      of the DNA capsulation and the membrane fusion with anionic liposomes, we found
      that MEL-A-containing liposomes increased both processes, but that MEL-B and MEL
      C-containing liposomes just increased either of them. The results indicated that
      these kinds of the physicochemical properties in MEL-A-containing liposomes are
      able to increase the efficiency of liposome-mediated gene transfection.

PMID- 17202681
TI  - Molecular authentication of Radix Puerariae Lobatae and Radix Puerariae Thomsonii
      by ITS and 5S rRNA spacer sequencing.
AB  - In the present study, we examined nuclear DNA sequences in an attempt to reveal
      the relationships between Pueraria lobata (Willd). Ohwi, P. thomsonii Benth., and
      P. montana (Lour.) Merr. We found that internal transcribed spacer (ITS)
      sequences of nuclear ribosomal DNA are highly divergent in P. lobata and P.
      thomsonii, and four types of ITS with different length are found in the two
      species. On the other hand, DNA sequences of 5S rRNA gene spacer are highly
      conserved across multiple copies in P. lobata and P. thomsonii, they could be
      used to identify P. lobata, P. thomsonii, and P. montana of this complex, and may
      serve as a useful tool in medical authentication of Radix Puerariae Lobatae and
      Radix Puerariae Thomsonii.

PMID- 17202682
TI  - Inhibitory effects of asiatic acid on 7,12-dimethylbenz[a]anthracene and 12-O
      tetradecanoylphorbol 13-acetate-induced tumor promotion in mice.
AB  - Asiatic acid, a pentacyclic triterpene, has been reported to induce apoptosis of
      various human cancer cells. In the present study, we assessed the anti-tumor
      promoting effect of asiatic acid against 12-O-tetradecanoylphorbol 13-acetate
      (TPA)-mediated skin tumorigenesis in 7,12-dimethylbenz[a]anthracene (DMBA)
      initiated ICR mice. Topical application of asiatic acid prior to each application
      of TPA resulted in a significant reduction in skin tumor formation. We also found
      that pre-application of asiatic acid alleviated TPA-induced [3H]thymidine
      incorporation, which is a conventional marker for skin tumor promotion. In
      addition, asiatic acid inhibited the TPA-induced generation of nitric oxide (NO)
      and expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2),
      which are known to play important roles in tumor growth, especially in the
      promotion stage. In addition, topical application of aminoguanidine (AG), a
      selective iNOS inhibitor, and N(G)-nitro-L-arginine-methyl ester (NAME), another
      iNOS inhibitor, 30 min prior to TPA treatment significantly inhibited the TPA
      induced COX-2 expression. These results suggest that asiatic acid may exert anti
      tumorigenesis through inhibitory actions in NO and COX-2 signals.

PMID- 17202683
TI  - A new 2-imino-1,3-thiazoline derivative, KHG22394, inhibits melanin synthesis in
      mouse B16 melanoma cells.
AB  - During our on-going attempts to develop a new skin-whitening agent, we identified
      a novel candidate compound KHG22394, a 2-imino-1,3-thiazoline derivative. Our
      data show that KHG22394 significantly inhibits melanin production in a dose
      dependent manner, but that it does not directly inhibit tyrosinase, the rate
      limiting melanogenic enzyme. It has been reported that the activation of
      extracellular signal-regulated kinase (ERK) reduces melanin synthesis by
      downregulating microphthalmia-associated transcription factor (Mitf). Thus, we
      examined the effects of KHG22394 on the ERK pathway and found that it induced ERK
      and 90 kDa ribosomal S6 kinase (RSK-1) activation. Moreover, alpha-melanocyte
      stimulating hormone (alpha-MSH) is known to increase melanin biosynthesis by
      increasing tyrosinase production, and here, we found that alpha-MSH-induced Mitf
      and tyrosinase increases were inhibited in B16 melanoma cells treated with
      KHG22394. These findings suggest that the hypopigmentary effect of KHG22394
      results from the downregulation of Mitf and subsequently of tyrosinase, although
      KHG22394 did not inhibit tyrosinase activity directly. Our findings indicate that
      2-imino-1,3-thiazoline derivatives are potential skin whitening agents.

PMID- 17202684
TI  - Antifungal effect of eugenol and nerolidol against Microsporum gypseum in a
      guinea pig model.
AB  - Essential oils have been widely used in anti-infectious application. In the
      present study, we elucidated the antifungal activities of eugenol and nerolidol
      isolated from Japanese cypress oil in a guinea pig model infected by Microsporum
      gypseum (M. gypseum). A minimal inhibitory concentration (MIC), skin lesion
      scoring, hair culture and histopathologic examination of skin tissues were
      performed to evaluate the antifungal effect of these oils. The MICs of eugenol,
      nerolidol and econazole (positive control) were 0.01-0.03% and 0.5-2% and 4-16
      microg/ml, respectively. Based on these MICs, eugenol and nerolidol were adjusted
      to 10% concentration with a base of Vaseline petroleum jelly and were applied
      topically to the skin lesion infected with M. gypseum daily for 3 weeks. Both
      eugenol and nerolidol were clinically effective at improving the lesion during
      the first week of application, as determined by skin lesion scoring. Nerolidol
      improved the skin lesions infected by M. gypseum, but eugenol did not, as
      determined in the hair culture test. Histopathologic examination revealed that
      the eugenol- and nerolidol-treated groups had a lower degree of hyperkeratosis
      and inflammatory cell infiltration than the positive control. Taken together,
      these results suggest that eugenol and nerolidol could apply supplementary
      antifungal agents.

PMID- 17202685
TI  - Protective effect of (4-methoxybenzylidene)-(3-methoxynophenyl)amine against
      neuronal cell death induced by oxygen and glucose deprivation in rat organotypic
      hippocampal slice culture.
AB  - Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural phytoalexin found in
      grape skin, and has been suggested to be an antioxidant agent, an anticancer
      agent and a cardioprotective agent. In particular, recent experimental evidence
      has demonstrated that resveratrol exhibits neuroprotective effects in various
      assay systems. During the study on the resveratrol derivatives, we found that (4
      methoxybenzylidene)-(3-methoxyphenyl)amine (MBMPA), which has blocked free
      phenolic groups, strongly protects neuronal cells against ischemic damage on a
      higher activity than resveratrol. The MBMPA potently reduced the level of
      neuronal cell death in an oxygen and glucose deprivation-exposed rat organotypic
      hippocampal slice culture. In addition, ATP depletion following the onset of
      oxygen and glucose deprivation in an adult hippocampal slice was blocked by the
      MBMPA treatment. These results suggest that MBMPA has a neuroprotective effect on
      an in vitro ischemia model, and may be useful for treating stroke.

PMID- 17202686
TI  - In vitro study for inhibition of NO production about constituents of Sappan
      Lignum.
AB  - In the course of our screening, we found that the methanolic extract of Sappan
      Lignum showed strong activity against lipopolysaccharide (LPS)-induced nitric
      oxide (NO) production by macrophages in vitro. As it was reported that Brazilin
      inhibited inducible NO gene, we conducted to similar tests for six known
      compounds isolated from Sappan Lignum, namely, brazilein, sappanchalcone,
      protosappanin A, protosappanin B, protosappanin C besides brazilin. And six
      compounds were also subjected to six tests to speculate their properties: (1)
      inhibition of NO production by cultured J774.1 (macrophage-like) cell line, (2)
      suppression of inducible NO synthase (iNOS) gene expression, (3) inhibition of NO
      production by murine peritoneal macrophages, (4) DPPH radical scavenging
      activity, (5) reduction of ferric ion and (6) antioxidant activity. Brazilein and
      sappanchalcone showed significant inhibition of lipopolysaccharide (LPS)-induced
      NO production by J774.1 cell line like Brazilin; 100% inhibition at 30 microM in
      test (1) and at 10 microM in test (3). The mechanisms underlying the inhibition
      of NO production by the compounds were investigated in test (2). As a result,
      brazilin was found to almost completely suppress iNOS gene expression at 100
      microM as reported, and brazilein and sappanchalcone also suppressed iNOS gene
      expression. But strong activities were not observed for protosappanins A, B and
      C. So, we conducted tests (4), (5) and (6) to investigate other properties about
      six compounds. Protosappanin A and Brazilin demonstrated high antioxidant
      activity compared with Vitamin E in tests (4) and (5). Protosappanin A and B
      inhibited the oxidation of linoleic acid in test (6). Among the dibenzoxocin
      derivatives, only protosappanin C did not show significant activity in all the
      tests. We found that sappanchalcone showed same activity as brazilin, and six
      compounds isolated from Sappan Lignum showed various properties.

PMID- 17202687
TI  - In vitro and in vivo antiallergic effect of the fructus of Evodia rutaecarpa and
      its constituents.
AB  - The unripe fruit of Evodia rutaecarpa (JUSS) BENTH (ER, Family Rutaceae) has been
      used frequently as a traditional medicine against inflammatory diseases in Korea,
      China and Japan. To evaluate antiallergic effect of ER, we isolated its main
      constituents, evodiamine and rutaecarpine, and evaluated in vivo their inhibitory
      effects against passive cutaneous anaphylaxis (PCA) reaction induced by IgE
      antigen complex and scratching behaviors by compound 48/80. ER and its
      constituents, evodiamine and rutaecarpine, potently inhibited PCA reaction and
      scratching behaviors in mice, although ER weakly inhibited scratching behaviors.
      Evodiamine and rutaecarpine inhibited TNF-alpha and IL-4 protein expression in
      RBL-2H3 cells induced by IgE-antigen complex, although these did not inhibit
      degranulation of RBL-2H3 cells induced by IgE-antigen complex and rat peritoneal
      mast cells induced by compound 48/80. These findings suggest that ER and its
      constituents, evodiamine and rutaecarpine, may be effective for IgE-induced
      allergic diseases such as atopic dermatitis and rhinitis.

PMID- 17202688
TI  - Differential effects of antioxidants on the in vitro invasion, growth and lung
      metastasis of murine colon cancer cells.
AB  - We conducted a comparative study of 20 antioxidants including antioxidative
      vitamins and polyphenols to examine their inhibitory activities against the in
      vitro invasion, growth and experimental lung metastasis of murine colon 26-L5
      carcinoma cells. Among the compounds tested, epigallocatechin gallate (EGCG),
      gallocatechin gallate and genistein exhibited significant reductions at 77%, 46%
      and 44% in tumor metastasis by an intraperitoneal administration for 5 d
      beginning at 3 d before tumor inoculation, respectively. Quercetin also showed a
      slight but not statistically significant inhibition. Alpha-tocopherol, beta
      carotene, ascorbic acid and 2 EGCG-related compounds of epicatechin gallate and
      epigallocatechin had no effect. EGCG also inhibited tumor metastasis dose
      dependently with 98% suppression at 2 micromol; and an almost equivalent
      inhibition was also produced by only pre-administration of EGCG at the same dose
      before tumor inoculation. EGCG significantly inhibited tumor cell invasion and
      proliferation, but its inhibition of these activities was much less effective
      than that of other compounds which did not show any antimetastatic effect. No
      statistically significant relationship was observed between the radical
      scavenging activities of the test compounds and their rates of inhibition of
      tumor metastasis. The antimetastatic mechanism of EGCG thus seems to be
      independent of its inhibition of tumor invasion and growth, as well as its
      radical scavenging activity. Our results suggest that EGCG is potentially
      beneficial for tumor metastasis inhibition.

PMID- 17202689
TI  - Human acyl-CoA: cholesterol acyltransferase inhibitory activities of aliphatic
      acid amides from Zanthoxylum piperitum DC.
AB  - Acyl-CoA: cholesterol acyltransferase (ACAT) plays an important role in the
      esterification of cholesterol with its substrates, cholesterol and fatty acyl
      coenzyme A, to facilitate both intracellular storage and intercellular transport.
      ACAT-1 is more involved in macrophage foam cell formation and ACAT-2 plays a
      critical role in the cholesterol absorption process in intestinal enterocytes.
      Three aliphatic acid amides, beta-sanshool (1), gamma-sanshool (2), and hydroxy
      beta-sanshool (3), were isolated by bioassay-guided fractionation of the
      ethanolic extracts of Zanthoxylum piperitum DC. Compounds 1 and 2 inhibited human
      ACAT-1 and -2 activities with IC50 values of 39.0 and 79.7 microM for 1 and of
      12.0 and 82.6 microM for 2, respectively. However, the hACAT-1 and -2 inhibitory
      activities of compound 3 having hydroxyl group were relatively less than those of
      compounds 1 and 2. A semi-synthetic compound 4, which has acetyl residue at 2'-OH
      of compound 3, exhibited the increased hACAT-1 and -2 inhibitory activities with
      IC50 values of 28.1 and 87.5 microM, respectively.

PMID- 17202690
TI  - Characterization of novel mixed polyethyleneglycol modified liposomes.
AB  - In our previous paper, mixed polyetheleneglycol (PEG) modification of liposomes
      by a mixture of 1-monomethoxypolyethyleneglycol-2,3-distearoylglycerol (PEG-DSG)
      with short polyoxyethylene chain and PEG-DSG with long one was shown to increase
      fixed aqueous layer thickness (FALT) around the liposomal membrane, and this was
      useful in vivo. In this study, we investigated the characterization of mixed PEG
      modification of liposomes with different anchors (PEG2000-DSG and PEG2000
      cholesterol (CHO)). When the liposomes was modified by a mixture of PEG2000-DSG
      and PEG2000-CHO, FALT was increased compared to that of each single PEG-lipids
      modification and the most suitable mix modification (PEG2000-DSG:PEG2000-CHO =
      3:1) showed a maximum FALT. This phenomenon was speculated to be based on the
      difference in the insertion state of the PEG anchor unit in the liposomal
      membrane. PEG-CHO-modified liposomes (single or mixed PEG-modified liposomes)
      were easily incorporated into the liposomal membranes compared with that of
      single PEG-DSG-modified liposomes. Namely, it was considered that the cholesterol
      anchor as a single chain was able to be easily introduced, compared with the DSG
      anchor as two chains, and induced some interaction with both PEG modification. In
      conclusion, it is expected that novel PEG-modified liposomes with PEG2000-DSG and
      PEG2000-CHO (3:1) had superior physicochemical properties.

PMID- 17202691
TI  - Stability indicating methods for the determination of norfloxacin in mixture with
      tinidazole.
AB  - Three stability indicating assay methods are developed for the determination of
      norfloxacin (Nor) in the presence of its decarboxylated degradation product and
      in mixture with tinidazole (Tnd). The proposed methods are reversed phase ion
      pair liquid chromatography (LC), thin layer densitometry (TLC) and second
      derivative ratio spectra zero crossing spectrophotometry ((2)DD). Chromatographic
      separation was achieved on mu-Bondapack C18 column 5 microm (300 mm x 3.9 mm,
      I.D.) and precoated silica gel TLC stationary phases for LC and TLC methods,
      respectively. Mobile phases consisting of phosphate buffer pH 3.2 : methanol (3 :
      1, v/v) containing 0.005 M pentane sulfonic acid sodium salt and isopropanol :
      butanol : concentrated ammonia : water (25 : 50 : 5 : 25, v/v/v/v) were used for
      resolution of Nor and Tnd by both techniques, respectively. Detection was carried
      at 280 nm. In the ratio spectra method, detection of Nor was carried at 282 nm.
      Linearity, accuracy and precision were found to be acceptable over concentration
      ranges of 20-225 microg/ml, 0.8-4 microg/spot and 1-7 microg/ml for Nor by LC,
      TLC and (2)DD methods and over concentration ranges of 37.5-375 microg/ml and 4.8
      20 microg/spot for Tnd by LC and TLC methods respectively. The suggested methods
      were successfully applied for the determination of both drugs in bulk powder,
      laboratory prepared mixtures and in commercial samples. Statistical comparison
      between the results obtained by the proposed and the reference methods was
      carried out using Student t-test, F ratio and one way ANOVA.

PMID- 17202692
TI  - Diastereomeric selective effects of double-stranded peptides conjugated with -Phe
      Phe- residue for growth inhibition and permeability of Ca(2+) on A431,
      src(ts)NRK, and A549 cells proliferation.
AB  - Our aim in this study is to elucidate the correlations between inhibition and
      chirality, especially, diastereomer, against cell proliferation of double
      stranded peptides. In previous studies, we reported on the design, synthesis, and
      chemical properties on a series of novel double-stranded peptides, (y-AA-x-AA)(2)
      spacer(S) (AA=amino acid, S=spacer, symbols x and y represent L- or D-forms, and
      (y-, x-) as represent of the symbol) conjugated with -y-AA-x-AA- and -z-AA-y-AA-x
      AA- sequences to a spacer of carbon number n. The inhibition of A431 and
      src(ts)NRK cells growth by four diastereomers of the N(1),N(12)-bis(y-Phe-x
      Phe)dodecanediamines (n=12) increased in the following order: (L-, L-)<(D-, D
      )<(L-, D-)<(D-, L-). A similar trend was seen in the order for the activity of (y
      AA-x-AA)(2)-spacer(S) with a spacer of carbon number n=2, 3, 4, 5, 6, and 12
      against the cell growth inhibition. To understand the mechanism of diasteromer
      selective cell growth inhibition, the correlations between chirality and cell
      growth inhibition were investigated from the measurement of the changes in
      cytosolic Ca(2+) concentration (=[Ca(2+)](c)) of A431 cells. Although less active
      N(1),N(12)-bis(L-Phe-L-Phe)dodecanediamine increases cytosolic [Ca(2+)](c), more
      active diasteromers, N(1),N(12)-bis(L-Phe-D-Phe)dodecanediamine and N(1),N(12)
      bis(D-Phe-L-Phe)dodecanediamine, decrease cytosolic [Ca(2+)](c) in A431 cell.
      This study provides diastereomeric effected new insights - this controls the
      polarity of double-stranded peptides - into the control of tumor cell
      proliferation and design of the uptake by penetration through the cell membrane
      of drugs.

PMID- 17202693
TI  - Triterpenoids from Hippophae rhamnoides L. and their nitric oxide production
      inhibitory and DPPH radical-scavenging activities.
AB  - In our investigation on the chemical constituents of Hippophae rhamnoides L., the
      chloroform-soluble fraction of the 80% acetone extract of branch bark was
      observed to inhibit nitric oxide (NO) production in a lipopolysaccharide and
      recombinant mouse interferon-gamma-activated murine macrophage-like cell line,
      RAW 264.7 cells. Two new triterpenoids, 2-O-trans-p-coumaroyl maslinic acid (1)
      and 2-O-caffeoyl maslinic acid (2), and three known triterpenoids, oleanolic acid
      (3), 3-O-trans-p-coumaroyl oleanolic acid (4), and 3-O-caffeoyl oleanolic acid
      (5), and 6-methoxy-2H-1-benzopyran (6) and beta-sitosterol (7) were isolated from
      the branch bark extract. Their inhibitory activities on the production of NO in
      RAW 264.7 cells and radical-scavenging activities were examined.

PMID- 17202694
TI  - Xanthones from stems of Hypericum chinense.
AB  - Six new xanthones, 4,6-dihydroxy-2,3-dimethoxyxanthone (1), 2,6-dihydroxy-3,4
      dimethoxyxanthone (2), 6-hydroxy-2,3,4-trimethoxyxanthone (3), 3,6-dihydroxy-1,2
      dimethoxyxanthone (4), 4,7-dihydroxy-2,3-dimethoxyxanthone (5), and 3,7-dihydroxy
      2,4-dimethoxyxanthone (6) were isolated from the stems of Hypericum chinense,
      together with four known xanthones. Their structures were established based on
      spectroscopic studies.

PMID- 17202695
TI  - Effects of plant lactones on the production of biofilm of Pseudomonas aeruginosa.
AB  - Sixteen plant sesquiterpene lactones, thirteen from four species of the Family
      Asteraceae, and three from a species of Hepaticae, as well as seven annonaceous
      acetogenins isolated from the seeds of the tropical tree Annona cherimolia
      (Family Annonaceae), were evaluated for their ability to inhibit or stimulate the
      production of biofilm by a strain of Pseudomonas aeruginosa. The tested compounds
      carry a gamma-lactone moiety in their structures. This structural feature is
      similar to the lactone moiety present in N-acyl homoserine lactones, compounds
      that play the important role of "quorum sensors" in the mechanisms of biofilm
      formation observed in many gram-negative bacteria. A special assay was employed
      to evaluate the influence of the tested plant compounds to inhibit or stimulate
      the production of biofilm in a P. aeruginosa wild strain. Most of the tested
      compounds affected the biofilm formation mechanism. Six sesquiterpene lactones
      isolated from Acanthospermum hispidum and one from Enydra anagallis as well as an
      acetogenin from Annona cherimolia strongly inhibited (69-77%) the biofilm
      formation when incorporated to a bacterial culture at a concentration of 2.5
      microg/ml. However, one of the acetogenins, squamocin, stimulated the biofilm
      formation even at a concentration of 0.25 microg/ml. The study of substances
      affecting the biofilm formation can lead to the design of new strategies to
      control P. aeruginosa infections.

PMID- 17202696
TI  - Synthesis, characterization and antioxidant activity of naringenin Schiff base
      and its Cu(II), Ni(II), Zn(II) complexes.
AB  - A new ligand, naringenin-2-hydroxy benzoyl hydrazone (H(5)L), was prepared by
      condensation of naringenin with 2-hydroxy benzoyl hydrazine. Its Cu(II), Ni(II),
      Zn(II) complexes have also been synthesized and characterized on the basis of
      (1)H-NMR, IR, UV-Vis spectra, elemental analyses, molar conductivity and thermal
      analyses. The general formula of these complexes was M(H(3)L) [M=Cu(II), Ni(II)
      and Zn(II)]. In addition, the antioxidant activities (superoxide and hydroxyl
      radical) of the free ligand and its complexes were determined in vitro. These
      compounds were found to possess potent antioxidant activity and be better than
      standard antioxidants like vitamin C and mannitol. In particular, the Cu(II)
      complex displayed excellent activity on the superoxide radical.

PMID- 17202697
TI  - Evaluation of the role of pores during strength testing in compacts made from
      different particle size fractions of sucrose.
AB  - The purpose of this study was to investigate the role of pores in the fracture of
      circular compacts and to predict compact properties and critical crack lengths.
      Four different particle size fractions of sucrose, ranging from 20 to 500 microm,
      were compressed into circular discs (i.e. flat tablets) and rectangular beam
      specimens of porosity between 30 and 14%. Modelling of the relationship between
      the tensile strength of the circular discs and the compact porosity indicated
      extensive fragmentation during compaction for particles in the size range of 250
      500 microm, accompanied by a change in densification mechanism for very coarse
      particles (355-500 microm). When determining the critical stress intensity factor
      from rectangular single edge notched beam specimens by 3-point bending, an
      apparent influence of particle size on the values could be seen, whereby here the
      results indicated that the critical particle size for fragmentation to occur is
      about 20-40 microm. It was possible to predict the critical stress intensity
      factor of the compacts from the median pore size and the tensile strength of the
      circular disc specimens by interpolation of the critical crack length for
      propagation to occur. The results indicated that for sucrose compacts regardless
      of their porosity, the pores themselves acted as stress concentrators, not as
      sharp cracks. For sucrose compacts, crack propagation hence proceeds most likely
      along grain boundaries.

PMID- 17202698
TI  - New C(28) steroidal glycosides from Tubocapsicum anomalum.
AB  - Three new C(28) steroidal glycosides, isotubocaposides A (1), B (2), and C (3),
      were isolated from the fruits of Tubocapsicum anomalum MAKINO. Their chemical
      structures were elucidated on the basis of spectroscopic and X-ray diffraction
      analysis of p-bromobenzoyl derivative (5) of isotubocaposigenin (4), the
      sapogenol derivative of these three glycosides. Isotubocaposides have the
      structural peculiarity of an unusual side chain carrying a C-21 bound to C-24 on
      the lactone ring.

PMID- 17202699
TI  - Scalable synthesis of (+)-2-amino-3-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic
      acid as a potent and selective group II metabotropic glutamate receptor agonist.
AB  - We successfully synthesized the potent and selective group II mGluR agonist (+)-1
      (MGS0008) via a process incorporating the key step of efficient fluorination of
      epoxide (+/-)-5c. This method would be adaptable to large-scale synthesis to
      produce (+)-1 in multi-gram quantities.

PMID- 17202700
TI  - QSAR studies on chalcones and flavonoids as anti-tuberculosis agents using
      genetic function approximation (GFA) method.
AB  - Design of compounds having good anti-tubercular activity is gaining much
      importance in the field of tuberculosis research due to reemergence of antibiotic
      resistance strains. In this paper quantitative structure activity relationships
      (QSAR) were developed on chalcones, chalcone-like compounds, flavones and
      flavanones to understand the relationship between biological activity and
      structural features. Genetic function approximation (GFA) method was used to
      identify the descriptors that would lead to good regression equations. The best
      molecular descriptors identified were Jurs descriptors (Jurs charged partial
      surface area), hydrogen bond donor, principal moment of inertia, molecular
      energy, dipole magnetic, molecular area, absorption, distribution, metabolism and
      excretion (ADME) properties and Chi indices (Kier & Hall chi connectivity
      indices). Excellent statistically significant models were developed by this
      approach (r(2)=0.8-0.97) for the four groups of compounds. The cross validated
      r(2) (XV r(2)) which is an indication of the predictive capability of the model
      for all the cases was also very good (=0.79-0.94).

PMID- 17202701
TI  - Analysis of the sesquiterpenoids in processed Atractylodis Rhizoma.
AB  - In Asia, processed Atractylodis Rhizoma, the dried rhizome of Atractylodes ovata
      De Candolle (Compositae), is widely used as a tonic agent in herbal diets; stir
      frying with soil is the most common processing method. In this study, we focused
      on determining variations in the function and concentrations of sesquiterpenoids
      in processed Atractylodis Rhizoma. Raw Atractylodis Rhizoma was processed by stir
      frying it with different assistant substrates (i.e., red soil and burnt clay).
      The results indicated that there was less atractylon in stir-fried materials than
      in raw materials. However, there were higher levels of atractylenolides II and
      III in stir-fried materials than in raw materials. We also found that the heavy
      metal content in burnt clay exceeded regulations set by the Taiwanese government.
      Moreover, commercial Atractylodis Rhizoma in Taiwan exhibited great differences
      in concentrations of the active components. In addition, atractylon showed
      stronger cytotoxicity than atractylenolides II and III in various cell lines.
      Therefore, we suggest that the toxic effects of atractylon are reduced following
      atractylon degradation to atractylenolides II and III. In conclusion, the
      toxicity of Atractylodis Rhizoma is reduced through processing.

PMID- 17202702
TI  - Bioactive saponins and glycosides. XXV. Acylated oleanane-type triterpene
      saponins from the seeds of tea plant (Camellia sinensis).
AB  - Seven new acylated oleanane-type triterpene oligoglycosides, theasaponins A(4)
      (1), A(5) (2), C(1) (3), E(8) (4), E(9) (5), G(1) (6), and H(1) (7), were
      isolated from the seeds of Japanese tea plant (Camellia sinensis). The structures
      of 1-7 were elucidated on the basis of chemical and physicochemical evidence.

PMID- 17202704
TI  - Exploring structural feature of aldose-reductase inhibition by 5-[[2-(omega
      carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives employing
      Fujita-Ban and Hansch approach.
AB  - Designing of a highly selective, potent and safe inhibitor of aldose reductase
      (ALR) capable of potentially blocking the excess glucose flux through the polyol
      pathway that prevails under diabetic condition has been a long standing
      challenge. In our study, we did quantitative structure-activity relationship
      (QSAR) analysis, based on Fujita-Ban and classical Hansch approach, on 5-[[2
      (omega-carboxyalkoxy)aryl]methylene]-4-oxo-2-thioxothiazolidine derivatives.
      Study gave structural insight into the binding mode of the molecules to the
      aldose reductase enzyme. The Fujita-Ban approach revealed that benzylidene
      thiazolidine nucleus is more potent as compare to naphthyl-methylene thiazolidine
      analogs. The bulkierness of naphthyl-methylene might be inquisitive with
      receptor. Hansch approach suggested that electron-withdrawing groups are
      conducive to aldose reductase inhibitory activity.

PMID- 17202703
TI  - Synthesis of novel curcumin analogues and their evaluation as selective
      cyclooxygenase-1 (COX-1) inhibitors.
AB  - Curcumin, a major yellow pigment and active component of turmeric, has been shown
      to possess anti-inflammatory and anti-cancer activities. Recent studies have
      indicated that cyclooxygenase-1 (COX-1) plays an important role in inflammation
      and carcinogenesis. In order to find more selective COX-1 inhibitors a series of
      novel curcumin derivatives was synthesized and evaluated for their ability to
      inhibit this enzyme using in vitro inhibition assays for COX-1 and COX-2 by
      measuring PGE(2) production. All curcumin analogues showed a higher rate of COX-1
      inhibition. The most potent curcumin compounds were (1E,6E)-1,7-di-(2,3,4
      trimethoxyphenyl)-1,6-heptadien-3,5-dione (4) (COX-1: IC(50) = 0.06 microM, COX
      2: IC(50) > 100 microM, selectivity index>1666) and (1E,6E)-methyl 4-[7-(4
      methoxycarbonyl)phenyl]-3,5-dioxo-1,6-heptadienyl]benzoate (6) (COX-1: IC(50) =
      0.05 microM, COX-2: IC(50) > 100 microM, selectivity index > 2000). Curcumin
      analogues therefore represent a novel class of highly selective COX-1 inhibitors
      and promising candidates for in vivo studies.

PMID- 17202705
TI  - Synthesis and pharmacological evaluation of some 3-(4-methoxyphenyl)-2
      substitutedamino-quinazolin-4(3H)-ones as analgesic and anti-inflammatory agents.
AB  - A variety of novel 3-(4-methoxyphenyl)-2-substitutedamino-quinazolin-4(3H)-ones
      were synthesized by reacting the amino group of 2-hydrazino-3-(4-methoxyphenyl)
      quinazolin-4(3H)-one with a variety of alkyl and aryl ketones. The starting
      material 2-hydrazino-3-(4-methoxyphenyl)-quinazolin-4(3H)-one was synthesized
      from 4-methoxyaniline. The title compounds were investigated for analgesic, anti
      inflammatory and ulcerogenic index activities. While the test compounds exhibited
      significant activity, compounds 2-(1-methylpropylidene)-hydrazino-3-(4
      methoxyphenyl)-quinazolin-4(3H)-one (A1), 2-(1-ethylpropylidene)-hydrazino-3-(4
      methoxyphenyl)-quinazolin-4(3H)-one (A2) and 2-(1-methylbutylidene)-hydrazino-3
      (4-methoxyphenyl)-quinazolin-4(3H)-one (A3) showed moderately more potent
      analgesic activity and the compound 2-(1-methylbutylidene)-hydrazino-3-(4
      methoxyphenyl)-quinazolin-4(3H)-one (A3) showed moderately more potent anti
      inflammatory activity when compared to the reference standard diclofenac sodium.
      Interestingly the test compounds showed only mild ulcerogenic potential when
      compared to aspirin.

PMID- 17202706
TI  - Jorunnamycins A-C, new stabilized renieramycin-type bistetrahydroisoquinolines
      isolated from the Thai nudibranch Jorunna funebris.
AB  - Jorunnamycins A-C (1a-c), three stabilized renieramycin-type
      bistetrahydroisoquinolines, were isolated from the mantles, the visceral organs,
      and the egg ribbons of the Thai nudibranch Jorunna funebris that was pretreated
      with potassium cyanide (KCN), along with five known compounds, renieramycins M
      (2m), N (2n), O (2o), and Q (2q) and mimosamycin (3). The structures of 1a-c were
      elucidated from spectroscopic data and by chemical conversion of renieramycin M
      (2m) into 1c via 1a. The chemical stability and the oxidative degradation
      generating simple isoquinoline alkaloids of a carbinolamine analog 1d, which was
      easily prepared by reacting 1c with silver nitrate in aqueous acetonitrile, are
      discussed. The results of cytotoxicity studies are also presented.

PMID- 17202708
TI  - Cantharimide dimers from the Chinese blister beetle, Mylabris phalerate PALLAS.
AB  - Five cantharidin-related compounds were isolated from the Chinese blister beetle,
      Mylabris phalerate PALLAS (Meloidae). Their structures were determined based on
      spectroscopic and chemical evidence. Three of them were identified as
      cantharimide dimers, which consist of two units of cantharimide combined with a
      tri-, tetra-, or penta-methylene group.

PMID- 17202707
TI  - Compressed oxygen in drug stability experiments.
AB  - A drug stability experiment accelerated by compressed oxygen was established. The
      stability of 10% ascorbic acid solution as a model was studied and the kinetic
      parameters were obtained with the newly established experimental method. Because
      ascorbic acid degrades under both anaerobic and aerobic conditions, the total
      rate constant k(total) can be expressed as: k(total)=k(anaerobic) + k(aerobic),
      where k(anaerobic) and k(aerobic) are the rate constants of anaerobic and aerobic
      degradations, respectively. The k(anaerobic) can be expressed as k(anaerobic) =
      A(anaerobic) x exp(-E(a,anaerobic)/RT) according to Arrhenius equation, and the
      k(aerobic) was found to be k(aerobic) = A(aerobic) x exp(-E(a,aerobic)/RT) x
      p(O2) in our study.

PMID- 17202709
TI  - Preparation of new nitrogen-bridged heterocycles. 59. Syntheses and
      intramolecular interactions of 3-(acylmethylthio)- and 3-[(3-ethoxycarbonyl-2
      propenyl)thio]thieno[3,4-b]indolizine derivatives.
AB  - Various thieno[3,4-b]indolizine derivatives having an acylmethylthio or (3
      ethoxycarbonyl-2-propenyl)thio group at the 3-position which could not be
      obtained by a conventional method were prepared by a new procedure using
      cyanoethyl group as a protecting group and their intramolecular arene-pi
      interactions were investigated. In the (1)H-NMR spectra of these thieno[3,4
      b]indolizines, the low-field shifts (delta 0.10-0.33 ppm) for the 5-protons were
      observed in comparison with those of 3-(methylthio)thieno[3,4-b]indolizines as a
      standard. The UV spectra also exhibited a characteristic absorption band at 425
      445 nm attributable to the arene-pi interaction but their intensities were
      generally lower than those of 3-(arylmethylthio)thieno[3,4-b]indolizines. In
      their X-ray analyses, the anti conformation for 3-(acylmethylthio)thieno[3,4
      b]indolizines and the gauche one for the 3-(3-ethoxycarbonyl-2-propenyl)thio
      derivatives were exhibited.

PMID- 17202710
TI  - Cytotoxic triterpenoid saponins from the roots of Cephalaria gigantea.
AB  - Three new oleanane-type saponins, giganteosides L (1), M (2) and N (3) along with
      eight known ones were isolated from the roots of Cephalaria gigantea. Their
      structures were established as 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D
      glucuronopyranosyl]-28-O-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]
      oleanolic acid, 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]
      28-O-[beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]-hederagenin, 3-O
      [alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-28-O-[beta-D
      glucopyranosyl-(1-->6)-beta-D-glucopyranosyl]-hederagenin, respectively, by means
      of spectroscopic methods (1D and 2D NMR, HR-ESI-MS). Cytotoxic activity of
      monodesmosides was investigated in vitro using three cancer cell lines, namely,
      human non pigmented melanoma MEL-5 and human leukemia HL-60. Giganteosides D (4)
      and E (5) showed antiproliferative effect on human cell lines with IC(50) values
      in the range 3.15-7.5 microM.

PMID- 17202711
TI  - Bioactive constituents from Chinese natural medicines. XX. Inhibitors of antigen
      induced degranulation in RBL-2H3 cells from the seeds of Psoralea corylifolia.
AB  - The ethyl acetate-soluble fraction of the methanolic extract from the seeds of
      Psoralea corylifolia was found to inhibit the release of beta-hexosaminidase, as
      a marker of antigen-IgE-induced degranulation in RBL-2H3 cells. Sixteen
      constituents were isolated from the ethyl acetate-soluble fraction and several
      constituents, Delta(1),3-hydroxybakuchiol (IC(50) = 49 microM), Delta(3),2
      hydroxybakuchiol (69 microM, bavachin (58 microM), and psoralidin (ca. 100
      microM), showed inhibitory activities against the antigen-induced degranulation.

PMID- 17202712
TI  - N-long-chain monoacylated derivatives of 2,6-diaminopyridine with antiviral
      activity.
AB  - N-Monoacyl-2,6-diaminopyridines (2a-c) and N,N'-diacyl-2,6-diaminopyridines (3a
      c) were synthesized from 2,6-diaminopyridine by acylation with the corresponding
      acyl halide or by dehydration with the corresponding carboxylic acid using 1,3
      dicyclohexylcarbodiimide (DCC). The antiviral activities of N-monoacyl- and N,N'
      diacyl-2,6-diaminopyridines (2a-c and 3a-c) were estimated using plaque reduction
      assay with HSV-1. All N-monoacyl derivatives (2a-c) showed significant anti
      herpes simplex virus (HSV)-1 activity (EC(50) = 15.3-18.5 microg/ml). The CC(50)
      values of 2a-c measured using Vero cells ranged at 37.5-50.0 microg/ml. These
      compounds showed no significant antibacterial activities with Escherichia coli or
      Staphylococcus aureus even at a concentration of 1 mg/ml. The N,N'-diacyl
      derivatives (3a-c) showed no significant anti-HSV-1 activity.

PMID- 17202713
TI  - Comparative studies on conventional and microwave assisted synthesis of
      benzimidazole and their 2-substituted derivative with the effect of salt form of
      reactant.
AB  - Benzimidazole and their derivative were reported to have wide biological
      activities and were synthesized by using different solvents and ring closing
      agents. The present work deals with the comparative synthesis of 2-alkyl and aryl
      substituted benzimidazole derivative in the presence of polyphosphoric acid
      through microwave and conventional methods and also studied the effect of salt
      form of reactant for completion of the reaction. The 2-substituted aryl and alkyl
      benzimidazole derivative were synthesized via microwave and was observed to be
      more beneficial, in respect of yield (increases up to 10 to 50%) and time (96 to
      98% was reduced) than conventional method of synthesis. This study was concluded
      that the salt form of reactant (o-phenylenediamine dihydrochloride) gave reduced
      colour impurities, homogenous mixing and reduced time for completion of reaction.

PMID- 17202714
TI  - Novel microbial transformations of sclareolide.
AB  - Fungal catalysis of sclareolide (1) using Mucor plumbeus (ATCC 4740),
      Cunninghamella blakesleeana (ATCC 9245), Cunninghamella echinulata (ATCC 9244),
      Curvularia lunata (ATCC 12017) and Aspergillus niger (ATCC 1004), was performed.
      Cunninghamella blakesleeana (ATCC 9245) metabolized compound 1 to afford O(6)
      sclareolide (2), 3beta,6alpha-dihydroxysclareolide (3), 9-hydroxysclareolide (4),
      along with three known metabolites, 1beta,3beta-dihydroxysclareolide (5), 3
      oxosclareolide (6) and 3beta-hydroxysclareolide (7). Biotransformation
      experiments of compound 1 with Cunninghamella echinulata (ATCC 9244) also yielded
      two new compounds, 5-hydroxysclareolide (8), and 7beta-hydroxysclareolide (9)
      along with two known compounds 5 and 7. Spectroscopic methods were used to
      establish the structures of compounds 2-9. Compounds 2-9 exhibited modest
      acetylcholinesterase inhibitory activity.

PMID- 17202715
TI  - A conventional new procedure for N-acylation of unprotected amino acids.
AB  - The preparation of amide derivatives (4) by N-acylation of unprotected alpha
      amino acids is easily achieved via readily available benzotriazolyl carboxylates
      (2a-d) or succinimidyl carboxylates (2e-f). These intermediates (2) are prepared
      from reaction of carboxylic acids (1) with 1-hydroxybenzotriazole (HO-Bt) or N
      hydroxysuccinimide (HO-Su) in the presence of equimolar amounts of 1-ethyl-3-(3'
      dimethylaminopropyl)carbodiimide hydrochloride (WSCI). The overall yields of the
      target compounds (4) were excellent, and this two-stage procedure could be
      applicable as an alternative procedure for one-pot reaction.

PMID- 17202716
TI  - Comparative study on major bioactive components in natural, artificial and in
      vitro cultured Calculus Bovis.
AB  - Major bioactive components in various Calculus Bovis, including natural,
      artificial and in-vitro cultured Calculus Bovis, were comparatively studied. An
      approach of high-performance liquid chromatography coupled with ultraviolet and
      evaporative light scattering detections (HPLC/UV/ELSD) was established to
      simultaneously determinate six bioactive components thereof, including five bile
      acids (cholic acid, deoxycholic acid, ursodeoxycholic, chenodeoxycholic acid,
      hyodeoxycholic acid) and bilirubin. ELSD and UV detector were applied to detect
      bile acids and bilirubin respectively. The assay was performed on a C(18) column
      with water-acetonitrile gradient elution and the investigated constituents were
      authenticated by comparing retention times and mass spectra with those of
      reference compounds. The proposed method was applied to analyze twenty-one
      Calculus Bovis extraction samples, and produced data with acceptable linearity,
      precision, repeatability and accuracy. The result indicated the variations among
      Calculus Bovis samples under different developmental conditions. Artificial and
      in-vitro cultured Calculus Bovis, especially in-vitro cultured ones, which
      contain total bioactive constituents no less than natural products and have the
      best batch-to-batch uniformity, suffice to be used as substitutes of natural
      Calculus Bovis.

PMID- 17202717
TI  - Two new megastigmanes from the leaves of Cucumis sativus.
AB  - Two new megastigmane, cucumegastigmanes I (1) and II (2), together with a known
      megastigmane, (+)-dehydrovomifoliol (3), and five other known compounds were
      isolated from the leaves of Cucumis sativus. The structures of the new compounds
      were elucidated from spectroscopic analysis and their absolute stereochemistries
      were determined in detail using the chemical conversion and a modified Mosher's
      method.

PMID- 17202718
TI  - Two new stereoisomers of Tetrahydrofuranoid lignans from the flower buds of
      Magnolia fargesii.
AB  - Two new stereoisomers of tetrahydrofuranoid lignans, 7S,8R,7'S,8'R- (1) and
      7R,8S,7'S,8'R-3,4,3',4'-tetramethoxy-9,7'-dihydroxy-8.8',7.O.9'-lignan (2) along
      with nine known lignans including tetrahydrofuranoids (3, 4) and
      tetrahydrofurofuranoids (5-11) were isolated from a CHCl(3)-soluble fraction of
      the flower buds of Magnolia fargesii. Two tetrahydrofuranoids, magnostellin A (3)
      and lariciresinol dimethyl ether (4) were isolated from this species for the
      first time. The structures of these compounds (1-11) were identified by
      spectroscopic methods as well as by comparison with published values. Absolute
      configurations of new stereoisomers (1, 2) were determined by the Mosher's
      esterification method and Circular Dichroism (CD) studies. All the isolates (1
      11) were evaluated for their antioxidant activities using modified superoxide
      radical-scavenging assay. Compounds 5-8 showed the potent superoxide radical
      scavenging activities with the ED(50) values of 19.2, 19.2, 16.5, and 27.7
      microM, respectively, as compared with standard antioxidants (BHA: 22.8 microM;
      Trolox: 940 microM).

PMID- 17202719
TI  - Post-harvest alteration of the main chemical ingredients in Ligusticum chuanxiong
      Hort. (Rhizoma Chuanxiong).
AB  - Rhizoma Chuanxiong (Ligusticum chuanxiong HORT.) is a commonly used traditional
      Chinese medicinal herb for the treatment of cardiovascular disorders. Significant
      variations of the main components in this herb were observed in commercial
      samples. The present study investigated effects of post-harvest drying and
      processing methods on nine main components in the herb. Results showed that
      drying at 60 degrees C or under the sun the contents of three major constituents,
      namely senkyunolide A (4), coniferylferulate (5) and Z-ligustilide (6), decreased
      significantly, while the contents of ferulic acid (1), riligustilide (8) and
      levistolide A (9) increased significantly. Senkyunolide I (2) and senkyunolide H
      (3), which were not detected in fresh herbs, appeared in dried samples. Similar
      chemical alterations, such as decrease in the contents of three major ingredients
      and increase in the contents of compounds 1, 2, 3, 8 and 9, were also observed in
      differently processed herbal samples. The possible converting mechanisms of these
      components were clarified by employing pure major components treated under the
      same conditions.

PMID- 17202720
TI  - Steroidal glycosides from Agave utahensis.
AB  - Three new spirostanol glycosides (1-3) and a new furostanol glycoside (4),
      together with two known spirostanol glycosides (5 and 6) were isolated from the
      whole plants of Agave utahensis (Agavaceae). The structures of the new compounds
      were determined by spectroscopic analysis and the results of hydrolytic cleavage.

PMID- 17202721
TI  - Lignans from Arctium lappa and their inhibition of LPS-induced nitric oxide
      production.
AB  - A new butyrolactone sesquilignan, isolappaol C (1), together with four known
      lignans, lappaol C (2), lappaol D (3), lappaol F (4), and diarctigenin (5), were
      isolated from the methanolic extract of the seeds from the Arctium lappa plant.
      The structure of isolappaol C (1) was determined by spectral analysis including
      1D- and 2D-NMR. All the isolates were evaluated for their inhibitory effects on
      the LPS-induced nitric oxide production using murine macrophage RAW264.7 cells.
      Lappaol F (4) and diarctigenin (5) strongly inhibited NO production in the LPS
      stimulated RAW264.7 cells with IC(50) values of 9.5 and 9.6 microM, respectively.

PMID- 17202723
TI  - Photo-oxidation of aldehydes with molecular oxygen in the presence of catalytic
      bromine or hydrobromic Acid.
AB  - Aldehydes were found to be oxidized with molecular oxygen to the corresponding
      carboxylic acid in the presence of catalytic hydrobromic acid or bromine under
      photo-irradiation.

PMID- 17202722
TI  - Chemical constituents of the style of Zea mays L. with glycation inhibitory
      activity.
AB  - A new sesquiterpene along with 15 known compounds were isolated from the style of
      Zea mays L. These structures were elucidated on the basis of spectroscopic
      analysis. The ability of these compounds to inhibit glycation in vitro was
      analyzed. This allowed determination of chemical functional groups required for
      the inhibition of glycation.

PMID- 17202724
TI  - Localization of type I myosin and F-actin to the leading edge region of the
      forespore membrane in Schizosaccharomyces pombe.
AB  - Myo1, a heavy chain of type I myosin of the fission yeast Schizosaccharomyces
      pombe, is essential for sporulation. Here we have analyzed the expression,
      localization and cellular function of the type I myosin light chain calmodulin,
      Cam2, encoded by cam2(+). Transcription of cam2(+) was constitutive and markedly
      enhanced in meiosis. The cam2 null mutant was viable and completed sporulation
      normally at 28 degrees C, but formed four-spored asci poorly at 34 degrees C. In
      those sporulation-defective cells, the forespore membrane was formed abnormally.
      A Cam2-GFP fusion protein accumulated at the cell poles in interphase cells and
      at the medial septation site in postmitotic cells, colocalizing with Myo1 and F
      actin patches. During the mating process, a single Cam2-GFP dot was detected at
      the tip of the mating projection. During meiosis-I, the Cam2-GFP dots dispersed
      into the cell periphery and the cytoplasm. At metaphase-II, intense Cam2-GFP
      signals appeared near Meu14 rings which were formed at the leading edge of
      expanding forespore membranes. This localization of Cam2 was dependent upon Myo1;
      and sporulation defect of cam2Delta at 34 degrees C was alleviated by
      overexpressing Myo1DeltaIQ. These results suggest a close relationship between
      Cam2 and Myo1. In addition, both F-actin and Myo1 localized with Cam2 in the
      leading edge region. In summary, type I myosin and F-actin accumulate at the
      leading edge area of the forespore membrane and may play a pivotal role in its
      assembly.

PMID- 17202725
TI  - Acute-onset autoimmune hepatitis.

PMID- 17202726
TI  - Efficacy and safety of micafungin in febrile neutropenic patients treated for
      hematological malignancies.
AB  - OBJECTIVE: The purpose of this study was to prospectively evaluate the efficacy
      and safety of micafungin (MCFG) in empirical therapy for febrile neutropenic
      patients for whom antibiotic therapy was not effective for hematological
      malignancies. PATIENTS AND METHODS: Twenty-three hematological patients aged 27
      82 years with febrile neutropenia for whom antibiotic therapy was not effective
      were enrolled in this study and responses to treatment were evaluated. RESULTS:
      Treatment success rate was 73.9%. Treatment success rates by primary diagnosis
      were 77.8% in patients with AML, 50.0% in patients with NHL and 87.5% in patients
      with other diseases. Moreover, MCFG at a dose of 100 mg or more have a tendency
      to be effective. One or more adverse events occurred in five (27.7%) of the
      patients during the study. All of these adverse events were below grade 2
      toxicity. CONCLUSIONS: Although the number of patients studied was limited, MCFG
      as a monotherapy seems to be effective and safe as an empirical therapy in
      patients with febrile neutropenia. However, further investigation using large
      scale studies is needed. This study demonstrated the clinical efficacy and safety
      of MCFG in patients with febrile neutropenia and with hematological malignancies.

PMID- 17202727
TI  - Diagnostic performance of pyogenic vertebral osteomyelitis.
AB  - OBJECTIVE: Early diagnosis of pyogenic vertebral osteomyelitis (PVO) is
      frequently difficult. There are, however, few studies that have investigated the
      diagnostic performance of PVO in Japan. Our aim was to analyze the diagnostic
      performance and identify clinical factors associated with the diagnostic delay of
      PVO. MATERIALS AND METHODS: We performed hospital-based retrospective case
      analysis. All patients with PVO were identified from the computerized medical
      database at Okinawa Chubu Hospital in Okinawa, Japan, from January 1985 to
      December 2004. We collected the following data; baseline information; laboratory
      tests; clinical and microbiologic outcomes; and diagnostic process. We used
      multivariable-adjusted linear regression to identify significant factors
      associated with patient and hospital delay to the diagnosis of PVO. RESULTS: We
      reviewed total of 209,428 patients hospitalized during the 20-year study period.
      Of those, we identified 51 patients with PVO. Eighty percent of these patients
      were misdiagnosed at their initial clinical encounters. Median duration from the
      symptom onset to the diagnosis was 19 days. Median durations of patient factor
      and hospital factor that contributed to the total delay were 1 and 8 days,
      respectively. Significant patient factor that contributed to delay was cognitive
      dysfunction. CONCLUSIONS: Cognitive dysfunction is a risk factor for patient
      delay for visiting physicians in patients with PVO. Diagnosis of PVO is difficult
      at the initial clinical encounter. High index of suspicion is needed for more
      rapid diagnosis of PVO.

PMID- 17202728
TI  - A retrospective review of 226 hospitalized patients with fever.
AB  - OBJECTIVE: To describe characteristics and outcomes for patients hospitalized
      with fever, not only patients with fever of unknown origin (FUO). METHODS:
      Medical records were reviewed for 226 consecutive patients hospitalized in a
      Japanese referral hospital with fever as one of the clinical problems. RESULTS:
      Although the majority of illnesses involved some sort of infection (54%),
      noninfectious inflammatory diseases, particularly adult Still's disease (n=6) and
      primary vasculitis syndromes (n=5) including 3 cases of Behcet's disease,
      represented the leading cause in patients who met the definition of FUO
      [16/51(31%)]. Tuberculosis (n=6) and psychological disorders (n=6) were
      associated with late diagnosis. However, there was only one patient meeting the
      definition of FUO among those with a psychological disorder. Among the patients
      with prolonged fever who did not strictly meet the definition of FUO, there was a
      considerable number of patients with critical illnesses, such as intra-abdominal
      abscess, polymyalgia rheumatica, sarcoidosis, ulcerative colitis, Castleman's
      disease, hematological and solid malignancies, and panhypopituitarism. Drug
      induced fever, systemic viral infection and unspecified vasculitis were difficult
      to definitively diagnose, although these pathologies were suspected as causes of
      fever. Follow-up of patients without definitive diagnosis at discharge confirmed
      that the fever subsided spontaneously or the cause of fever was properly treated
      after diagnosis in every patient and that none died of the underlying febrile
      illness. CONCLUSIONS: The present findings, from all patients displaying fever at
      hospitalization, are in agreement with findings from prior FUO series. Strict use
      of the definition of FUO is thus unwarranted when managing patients with
      prolonged fever.

PMID- 17202729
TI  - The causes of hypercalcemia in Okinawan patients: an international comparison.
AB  - OBJECTIVE: Our objective was to determine the causes and relative prevalence of
      hypercalcemia in patients at a major community hospital in Okinawa, Japan.
      Additionally, we compared these causes of hypercalcemia with the previously
      published international data. MATERIALS AND METHODS: We analyzed all patients
      with hypercalcemia in a community teaching hospital in Okinawa, Japan, from 1999
      to 2002 and determined the cause of hypercalcemia in each patient. We also
      performed a literature review of the original articles describing causes of
      hypercalcemia in patients from Eastern as well as Western countries. RESULTS: We
      identified 145 patients with hypercalcemia (median age, 69; range, 22 to 97).
      Major causes included malignant disorders (n=100; 69%), primary
      hyperparathyroidism (n=31; 21%), vitamin D-induced (n=4; 3%), and miscellaneous
      or unknown cause in 11 (8%). Among malignant disorders, adult T cell leukemia was
      the most frequent (n=35), being followed by lung cancer (n=25). Breast carcinoma
      was less prevalent (n=4). CONCLUSION: The major causes of hypercalcemia are
      malignancy and primary hyperparathyroidism in Okinawan Japanese patients. Adult T
      cell leukemia and lung carcinoma are among the top leading malignancies, while
      breast carcinoma is less frequent in this patient population. The etiologic
      prevalence of hypercalcemia in the Eastern population including Okinawans is
      significantly different from that in the Western population.

PMID- 17202731
TI  - Sibling cases of Addison's disease caused by DAX-1 gene mutations.
AB  - We report two sibling cases of Addison's disease without any evidence of sexual
      precocity, adrenal hyperplasia, or autoimmune disease. The diagnosis of primary
      adrenocortical insufficiency was made at the age of 5 in the younger brother and
      at the age of 18 in the elder brother. The younger brother had been inactive
      during infancy and had diffuse skin pigmentation without abnormal external
      genitalia, while the elder brother had been healthy until the age of 17 when he
      noticed skin pigmentation and small testes. Both boys had delayed puberty due to
      hypogonadotropic hypogonadism. The diagnosis of adrenal hypoplasia congenita
      (AHC) was established by genetic analysis of DAX-1 gene (dosage-sensitive sex
      reversal-adrenal hypoplasia gene on the X chromosome, gene 1) with the same
      single frameshift mutation (305delG). However, yet-uncharacterized epigenetic,
      nongenetic and/or genetic factors other than the DAX-1 gene may be responsible
      for the differential onset of AHC in these sibling cases.

PMID- 17202730
TI  - Development of hepatocellular carcinoma (HCC) in a patient 17 years after
      recovery from chronic hepatitis B and seroconversion to anti-HBs.
AB  - A 63-year-old man was admitted to hospital in 2003 for treatment of a
      hepatocellular carcinoma (HCC). He was negative for HBs antigen (HBsAg) and anti
      HCV antibody, and positive for anti-HBs. He had a past history of chronic
      hepatitis B. In 1986, HBsAg had become negative with the development of anti-HBs.
      In 2003, an HCC was detected and liver resection was carried out. Histological
      examination revealed moderately differentiated HCC and slightly fibrotic liver.
      It is suggested that a diagnosis of HCC, combined with negativity for HBsAg and
      anti-HCV antibody, may include cases of past recovery from chronic hepatitis B,
      such as this case.

PMID- 17202732
TI  - Fulminant pneumatosis intestinalis in a patient with diabetes mellitus and
      minimal change nephrotic syndrome.
AB  - We report a case of pneumatosis intestinalis in a diabetic patient with minimal
      change nephrotic syndrome, receiving immunosuppressive drugs and an alpha
      glucosidase inhibitor. The patient was a 72-year-old female, who suffered from
      right lower abdominal pain. Abdominal CT showed massive air in the intestinal
      wall, compatible with pneumatosis intestinalis. Her general condition rapidly
      deteriorated with systemic inflammatory response syndrome. The patient had
      received respiratory support for a week, along with antimicrobial therapy and
      continuous hemofiltration, and then recovered. Even though pneumatosis
      intestinalis is generally recognized as a mild disease, careful attention is
      necessary when it follows a serious condition.

PMID- 17202733
TI  - Sleep stage determines the expression pattern of sleep apneas.
AB  - We report on an obese man with sleep stage-dependent apnea. His type of apnea was
      predominantly central during non-rapid eye movement (NREM) sleep, while it was
      obstructive during rapid eye movement (REM) sleep. We found significantly more
      and more severe apneas during REM sleep compared to NREM sleep. His apneas were
      remarkably reduced by position adjustment, suggesting that upper airway collapse
      played a key role in the induction of both types of apnea. As his apneic patterns
      were dependent on the sleep stages, we assumed that the balance between upper
      airway obstruction and instability of central respiratory control might be
      important in determining the expression types.

PMID- 17202734
TI  - Pulmonary-renal syndrome, diffuse pulmonary hemorrhage and glomerulonephritis,
      associated with Wegener's granulomatosis effectively treated with early plasma
      exchange therapy.
AB  - We present a case of a 38-year-old Japanese man with Wegener's granulomatosis
      complicated with pulmonary-renal syndrome, i.e., diffuse pulmonary hemorrhage and
      rapidly progressive renal glomerulonephritis. As this is a life-threatening
      condition, we promptly initiated plasma exchange with intravenous
      methylprednisolone therapy. Diffuse pulmonary hemorrhage and renal failure were
      markedly improved. This case merits presentation because there are few clinical
      studies of the treatment of Wegener's granulomatosis with pulmonary-renal
      syndrome, particularly with pulmonary hemorrhage.

PMID- 17202735
TI  - Ten centimeter elevation of the contralateral leg is enough to evaluate Hoover
      sign.

PMID- 17202736
TI  - A hyperparathyroid state in a patient with glycyrrhetinic acid-induced
      pseudoaldosteronism.

PMID- 17202737
TI  - Emphysematous pyelonephritis.

PMID- 17202738
TI  - Beau's lines after chemotherapy for ALL.

PMID- 17202739
TI  - Diagnostic contribution of sputum cytology in a case of non-Hodgkin lymphoma.

PMID- 17202740
TI  - Leukemia cutis.

PMID- 17202741
TI  - Short history of epidemiology for noninfectious diseases in Japan. Part 1:
      selected diseases and related episodes from 1880 through 1944.

PMID- 17202742
TI  - Geographic difference of mortality of Creutzfeldt-Jakob disease in Japan.
AB  - BACKGROUND: The geographic mortality difference of Creutzfeldt-Jakob disease is
      still unclear in Japan. METHODS: Using vital statistics of Japan for 6 year
      period between 1999 and 2004 officially published by the government, we observed
      the mortality from Creutzfeldt-Jakob disease (ICD-10th: A81.0 and A81.8) by
      prefecture. Standardized mortality ratios were calculated for the 47 prefectures.
      RESULTS: For the observed 6 years, a total of 792 deaths from Creutzfeldt-Jakob
      disease were observed whole in Japan. Two prefectures, Akita and Yamanashi,
      presented significantly high standardized mortality ratios. In addition, Tochigi,
      Kochi, and Nagasaki showed standardized mortality rates higher than 1.5 without
      significance. No prefecture had significantly low standardized mortality ratios.
      CONCLUSION: Some prefectures with high mortality rate from Creutzfeldt-Jakob
      disease existed in Japan. Some of them had high incidence rate in a survey
      conducted in 1996 as well.

PMID- 17202743
TI  - Vitamin D receptor polymorphism among rickets children in Mongolia.
AB  - BACKGROUND: It was reported that 32% of children under five years old in Mongolia
      had symptoms of rickets. Vitamin D receptor (VDR) gene polymorphism has received
      attention in relation to bone metabolism. We therefore investigated whether VDR
      polymorphism is related to high prevalence of rickets in Mongolia and to bone
      properties in childhood. METHODS: We conducted a case-control study in
      Ulaanbaatar involving 80 children aged 7-10 years with a history of rickets
      (cases) and 72 children with no history of rickets (controls). VDR polymorphism
      was assessed using BsmI, ApaI, and TaqI, and bone properties were determined by
      measuring age standardized tibial cortical speed of sound (TCSOS). FINDINGS: Each
      allelic frequency was verified to satisfy the Hardy-Weinberg equilibrium in
      cases, controls, and the total sample. The VDR polymorphisms among cases (BB 3%,
      Bb 18%, bb 80%; AA 15%, Aa 38%, aa 47%; and TT 81%, Tt 17%, tt 3%) did not differ
      significantly from those among controls (BB 1%, Bb 13%, bb 86%; AA 16%, Aa 46%,
      aa 38%; and TT 86%, Tt 13%, tt 1%). There were no significant differences in
      TCSOS according to the VDR genotype among either cases or controls. CONCLUSIONS:
      The VDR polymorphism does not play a major role in the development of rickets in
      Mongolia and has no effect on TCSOS in childhood.

PMID- 17202744
TI  - Methyl-beta-cyclodextrin prevents Ca2+-induced Ca2+ release in smooth muscle
      cells of mouse urinary bladder.
AB  - We examined the effects of methyl-beta-cyclodextrin (MbetaCD) on Ca(2+)-induced
      Ca(2+) release (CICR) in smooth muscle cells (SMCs) of mouse urinary bladder
      (UB). Short depolarization of UBSMCs under voltage-clamp elicited several local
      Ca(2+) transients (Ca(2+) hot spots) via CICR within 20 ms in discrete sub
      sarcolemmal areas. Then, the Ca(2+) wave spread to whole areas. The pretreatment
      with 10 mM MbetaCD significantly attenuated Ca(2+) hot spots in UBSMCs and
      reduced contraction by single direct electrical pulse stimulation in UBSM strips.
      MbetaCD may prevent CICR by attenuating the coupling between voltage-dependent
      Ca(2+) channels and ryanodine receptors in Ca(2+) hot spot areas.

PMID- 17202745
TI  - Effects of edaravone on singlet oxygen released from activated human neutrophils.
AB  - The effects of edaravone, a curative agent for acute brain infarction, on singlet
      oxygen ((1)O2) released from activated human neutrophils were examined, and the
      effects were compared to those of histidine, a (1)O2 singlet oxygen scavenger.
      The neutrophils, stimulated with opsonized zymosan, released (1)O2 that was
      detected by chemiluminescence using a (1)O2 specific probe, trans-1-(2'
      methoxyvinyl)pyrene. Edaravone dose-dependently suppressed the (1)O2 release with
      an IC(50) of approximately 0.3 microM, while the IC(50) of histidine was
      approximately 1 mM. This (1)O2 scavenging activity of edaravone might be involved
      in its curative effects on acute brain infarction.

PMID- 17202746
TI  - A sensitive gait parameter for quantification of arthritis in rats.
AB  - Quantification of arthritis is helpful for investigating pain mechanisms of
      arthritis and for developing new drugs. We assessed and identified a feasible
      parameter for quantification of rat arthritis using a novel gait analyzing
      system. Knee-joint injection with small doses of lambda-carrageenan decreased
      swing time ratio (STR, swing time of the non-treated hindlimb/swing time of the
      lambda-carrageenan-injected hindlimb) in a dose-dependent manner. Intraperitoneal
      treatment with indomethacin restored the decreased STR dose-dependently. The
      arthritis could not be accurately quantified by swing time and swelling, common
      indices of arthritis. These results show that STR is a sensitive, reliable
      parameter for quantification of arthritis.

PMID- 17202747
TI  - Tacrolimus (FK506), an immunosuppressive agent, prevents indomethacin-induced
      small intestinal ulceration in the rat: inhibition of inducible nitric oxide
      synthase expression.
AB  - We examined the effect of tacrolimus (FK506), an immunosuppressive drug, on
      indomethacin-induced small intestinal ulceration in rats. Animals were given
      indomethacin (10 mg/kg, s.c.), killed 24 h later, and myeloperoxidase (MPO)
      activity and thiobarbituric acid reactants (TBARS) were evaluated in intestinal
      lesions. Tacrolimus (0.3 - 3 mg/kg) was administered p.o. twice 0.5 h before and
      6 h after indomethacin injection. The expression of inducible nitric oxide
      synthase (iNOS) mRNA was determined by a TaqMan real-time RT-PCR, while the
      activity of nuclear factor (NF)-kappaB DNA-binding was analyzed by
      electrophoresis mobility shift assays (EMSA) 6 h after indomethacin treatment.
      Indomethacin provoked severe hemorrhagic lesions in the small intestine, mainly
      in the jejunum and ileum, accompanied with increases in MPO activity and TBARS.
      Oral administration of tacrolimus reduced the severity of indomethacin-induced
      intestinal lesions in a dose-dependent manner. The increases in MPO activity and
      TBARS were also significantly attenuated by tacrolimus. The expression of iNOS
      mRNA was markedly enhanced when examined 6 h after indomethacin administration,
      and this response was counteracted by tacrolimus. Indomethacin also activated NF
      kappaB in a tacrolimus-preventable manner. These results suggest that tacrolimus
      prevents indomethacin-induced small intestinal ulceration in the rat. This effect
      may be due to inhibition of iNOS induction through suppression of NF-kappaB
      activation.

PMID- 17202748
TI  - Nicorandil elevates tissue cGMP levels in a nitric-oxide-independent manner.
AB  - The K(+) channel opener nicorandil is a hybrid compound that contains nitrate in
      its structure. It has been reported that nicorandil can relax vascular tissue in
      vitro via a mechanism that involves activation of K(ATP) channels and stimulation
      of soluble guanylyl cyclase. However, it is not known whether the increase of
      cGMP levels occurs through an elevation of nitric oxide (NO). The aim of the
      present study was to determine whether NO release was a direct effect of
      nicorandil. We reported here that nicorandil did not generate NO using ozone
      chemiluminescence detection methods in human or rat liver microsomes (P450-rich
      fractions) with addition of NADPH. However, nicorandil elevated cGMP levels in
      rat liver, aorta, and human coronary smooth muscle cells in vitro. The elevation
      was not inhibited by the NO trapping agent carboxy-2-phenyl-4,4,5,5-tetramethyl
      imidazoline-1-oxyl-3-oxide (carboxy-PTIO). These results suggest that nicorandil
      elevates cGMP without NO generation.

PMID- 17202749
TI  - Recent advances in technologies for analyzing protein kinases.
AB  - Most cellular events are regulated by protein phosphorylation mediated by protein
      kinases, whose malfunction is involved in the etiology of various disorders. The
      elucidation of the biochemical properties of the protein phosphorylation reaction
      will lead not only to a better understanding of the signal transduction
      mechanism, but also to developing new therapeutic agents. In this review, we
      briefly summarize the technologies to detect or characterize protein kinases with
      special emphasis on recently developed and/or commercially available techniques.

PMID- 17202750
TI  - Effects of 3-methyl-4-nitrophenol in diesel exhaust particles on the regulation
      of reproductive function in immature female Japanese quail (Coturnix japonica).
AB  - In a previous study, we found that 3-methyl-4-nitrophenol (PNMC), a component of
      diesel exhaust particles and also a degradation product of the insecticide
      fenitrothion, exhibits reproductive toxicity in the adult male Japanese quail.
      The present study investigated the toxicity of PNMC in the female Japanese quail
      and its ability to influence reproduction in immature females. The quail (21-day
      old) were injected intramuscularly (im) with PNMC at doses 0.1, 1 or 10 mg/kg
      body weight daily for 3 days. There was no significant difference in body growth
      between the PNMC-administered and control birds. However, the weights of the
      oviducts were significantly lower in the PNMC-treated birds at all doses.
      Furthermore, the plasma concentrations of luteinizing hormone (LH) and estradiol
      17 beta were significantly decreased with 1 and 10 mg/kg of PNMC. These findings
      suggest that PNMC might influence the hypothalamo-pituitary-gonadal axis with
      decreasing in secretion of GnRH, LH and ovarian steroid hormones and subsequently
      disturb growth of the reproductive organs of immature female quail. This study
      indicates that PNMC induces reproductive toxicity at the central level and
      disrupts reproductive function in the immature female quail.

PMID- 17202751
TI  - Assessment of urinary gonadotropin and steroid hormone profiles of female
      cynomolgus monkeys after treatment with Pueraria mirifica.
AB  - This study investigated the changes in the urinary hormone levels of female
      monkeys (Macaca fascicularis) after single-dose and long-term treatments with
      Pueraria mirifica (PM). The monkeys were separated into 3 groups (n=3) and orally
      treated with 10, 100, or 1,000 mg of PM in each group. Two series of experiments
      were performed. In the first series of experiments, the monkeys were orally
      treated with a single dose of PM. The experimental schedule was divided into a
      one menstrual cycle pretreatment period and a two menstrual cycle post-treatment
      period. In the second series of experiments, the monkeys were orally treated
      daily with PM for 90 days. The experiment schedule was divided into a one
      menstrual cycle pretreatment period, a three menstrual cycle treatment period,
      and a two menstrual cycle post-treatment period. Urinary samples were collected
      daily and assayed for the FSH, LH, estradiol, and progesterone levels. The
      results showed that there were no changes in the FSH, LH, estradiol, and
      progesterone levels after treatment with a single dose of 10, 100, or 1,000 mg of
      PM or after daily treatment with 10 mg of PM for 90 days compared with the levels
      observed during the pretreatment period. Daily treatment with 100 mg and 1,000 mg
      of PM for 90 days only produced a clear reduction in the urinary FSH levels. This
      suggests that changes of urinary FSH levels can be considered an indicator for
      study of estrogenic effects on hormonal levels in female monkeys.

PMID- 17202752
TI  - [Roles of oxidative stress in photoaging and the pathogenesis of systemic
      sclerosis].
AB  - Human skin is exposed to high amount of solar ultraviolet (UV) radiation, as well
      as to other environmental oxidants. Photoaging refers to the effect of long-term
      UV exposure and sun damage superimposed on intrinsically aged skin. The clinical
      photoaging features are dyspigmentation, laxity, wrinkles, and cutaneous
      malignancies. Most conspicuous photoaging change in dermis, which is caused by
      elastin materials accumulation, is termed "solar elastosis". Reactive oxygen
      species are known to be generated by UV radiation, and play an important role of
      photoaging. Although the pathogenesis of systemic sclerosis (SSc) remains
      unknown, oxidative stress has been suggested to contribute to clinical
      manifestations associated with SSc, such as vascular damage including Raynaud's
      phenomenon. This review focuses on recent data including our data which have
      demonstrated the critical role of oxidative stress in photoaging and the
      pathogenesis of SSc.

PMID- 17202753
TI  - [Lymphocyte trafficking and immunesurveillance].
AB  - The homeostasis of the immune system is maintained by the recirculation of naive
      lymphocytes through the secondary lymphoid tissues, such as the lymph nodes,
      Peyer's patches and spleen. Upon antigen encounter in the secondary lymphoid
      tissues, lymphocytes become activated and undergo a reprogramming of their
      trafficking properties. Most antigen-experienced lymphocytes traffic through the
      secondary lymphoid organs, but they can also migrate to extralymphoid tissues,
      where they exert effector functions. Dendritic cells in the secondary lymphoid
      tissues are crucial for the reprogramming of trafficking properties of activated
      T-lymphocytes. The exquisite specificity of such lymphocyte trafficking is
      determined by tissue-specific guidance signals expressed by the vascular
      endothelial cells, combined with counter receptors expressed by circulating
      lymphocytes. The high endothelial venules can selectively recruit naive
      lymphocytes into the lymph nodes and Peyer's patches by expressing a unique
      combination of vascular addressins and chemoattractants. The inflamed
      postcapillary venules in extralymphoid tissues also use a distinct array of
      endothelial adhesion molecules and tissue selective chemokines to support the
      recruitment of effector and memory lymphocytes that express appropriate
      trafficking receptors. Exit of lymphocytes from lymphoid and extralymphoid
      tissues into circulation is actively regulated by signals through specific
      receptors for sphingosine-1-phosphate and a certain chemokine(s), respectively.
      This review summarizes the present understandings of the mechanisms regulating
      homeostatic recirculation of naive lymphocytes through the secondary lymphoid
      tissues and tissue-specific trafficking of antigen-experienced lymphocytes.

PMID- 17202754
TI  - [Changes of complement in recurrent abortion and pregnancy loss with
      antiphospholipid antibody positive].
AB  - In order to know the comlement activation, the changes of compliment were
      evaluated in recurrent abortion and pregnancy loss patients with antiphospholipid
      antibody (APA) positive. Serum samples were taken from 82 patients with more than
      2 recurrent abortion patients and/or pregnancy loss. Fifty eight cases of 82
      patients were APA and antinuclear antibody negative without autoimmune disease.
      Anticardiolipin antibody (ACA), anti CL/beta2-GPI antibody (CL/beta2-GPI) were
      measured using ELISA. Lupus anticoagulant (LAC) was measured using diluted RVVT.
      CH50 and C3 and C4 were measured as complements. The number of positive cases of
      ACA, CL/beta2-GPI, LAC was 23, 9 and 5 cases, respectively. RESULTS: The levels
      (mean+/-SD) of CH50, C3 and C4 in ACA positive and negative cases were 38.8+/-8.3
      U/ml, 82.7+/-20.1 mg/dl, 18.5+/-5.7 mg/dl and 42.4+/-6.9 U/ml, 93.5+/-17.6 mg/dl,
      21.1+/-4.6 mg/dl, respectively. The levels of CH50, C3 and C4 in positive cases
      were significantly lower than negatives. The levels of CH50, C3 and C4 in
      CL/beta2-GPI and LAC positive cases were also significantly lower than negatives.
      CONCLUSION: The comlement activation was demonstrated in recurrent abortion and
      pregnancy loss with antiphospholipid antibody positive.

PMID- 17202756
TI  - [A case of systemic lupus erythematosus associated with thrombotic
      thrombocytopenic purpura and hemophagocytic syndrome].
AB  - THE CASE: A 44-year-old female. Developed polyarthralgia in August 2002. The
      patient was diagnosed with systemic lupus erythematosus (SLE) in November, due to
      polyarthralgia, leukopenia, anti ds-DNA antibody positive, antinuclear antibody
      positive, and false positive serologic test for syphilis. Hypocomplementemia
      continued even after the steroid treatment was conducted with insufficient
      control. In November 2003, ran fever and observed polyarthralgia. In December,
      gross hematuria and purpura appeared. The patient was hospitalized on December
      25. Thrombotic thrombocytopenic purpura (TTP) was suspected from the emergence of
      fragmented red cells, hemolysis, thrombocytopenic purpura, headache, renal
      dysfunction and fever. As hemophagocytic syndrome (HPS) was suspected from hyper
      ferritinemia, bone marrow aspiration was conducted. Macrophage confirmed
      hemophagocytic image and the patient was diagnosed with HPS complication.
      Methylprednisolone pulse therapy was conducted for three days, followed by the
      administration of prednisolone 60 mg. Plasma exchange therapy was also conducted
      from the first day of hospitalization. Recurrence of TTP after plasma exchange
      therapy, but it improved by additional plasma exchange. Low vWF-CP (ADAMTS-13)
      activity was observed in this case, and anti-vWF-CP antibody was positive. TTP
      and HPS are both critical intractable complications of SLE. Bearing in mind the
      possibility of simultaneous complication of both symptoms, prompt diagnosis is
      crucial for life-saving.

PMID- 17202755
TI  - [A case of systemic scleroderma complicating pulmonary hypertension].
AB  - The patient was a 7-year-old girl. At the age of 6, deposits of pigment had
      appeared on the skin of her face and limbs, the skin had become sclerosed, and
      she had developed dyspnea on exertion. Her previous physician had hospitalized
      her. She was diagnosed as systemic scleroderma that accompanied pulmonary
      hypertension by her symptoms and laboratory findings. She was referred to our
      hospital at 7 years of age, and she was hospitalized. At that time, the entire
      skin showed deposition of brown pigment, the skin of the limbs was sclerotic. And
      the face was mask-like, flexion of the joints of the fingers and knees was
      limited, and the fingertips were ulcerated. Raynaud's phenomenon was present. She
      was positive for antinuclear antibodies, and negative for other autoantibodies.
      Echocardiography revealed pulmonary hypertension. After admission, steroid pulse
      therapy and cyclophosphamide (CY) pulse therapy were initiated, and for
      aftercare, 15 mg/day of prednisolone (PSL) and mizolibin (MZB) were administered
      orally. After several months, the sclerosis of the skin improved and the
      restriction of limb flexion was almost eliminated. The pulmonary hypertension
      advanced temporarily (maximum: 70 mmHg), but after oral administration of a PGI2
      preparation and low-flow supplemental oxygen therapy and the initiation of
      anticoagulant therapy, the systolic pressure of the pulmonary artery improved to
      34 mmHg. The CY pulse therapy was terminated after two years, and internal use of
      PSL and MZB was continued. The patient's condition is now stable. This case was
      treated from an early stage with steroid pulse therapy and CY pulse therapy,
      accompanied with oral administration of a PGI2 preparation for the pulmonary
      hypertension. The dermal symptoms improved, and it was possible to maintain a
      state of remission.

PMID- 17202757
TI  - Use of IC tags in short-term carcinogenicity study on CB6F1 TGrasH2 mice.
AB  - We studied the effect of IC tags, subcutaneously implanted animal identification
      tools, on rasH2 mice. A 26-week short-term carcinogenicity study was performed on
      a total of 299 mice including 75 male and female rasH2 mice each, and 74 male and
      75 female non-Tg mice from the same litter as the rasH2 mice divided into a non
      IC tag group, the IC-tag group, acetone group, TPA group and MNU group (all of
      the animals except for those in the non-IC tag group) had IC tags implanted
      subcutaneously in their backs. The administration methods of the positive control
      drugs TPA (2.5 micro g/kg, 3 times/week, percutaneously) and MNU (75 mg/kg,
      single intraperitoneal injection) were based on the protocol of the ILSI/HESI
      international collaborative study. The results showed no differences in the
      tumorigenic incidence and organs developing tumors between the IC tag and non-IC
      tag groups in both rasH2 and non-Tg mice. In the positive control MNU group, the
      tumorigenic incidence and organs developing tumors were the same as the
      background data and no promotion of carcinogenesis was observed. In all IC tag
      groups including the TPA group and MNU group, a fibrous capsule was formed around
      the IC tags subcutaneously, but no inflammatory changes or neoplastic changes
      were observed. From these findings, it was concluded that the IC tag has no
      effect on a 26-week carcinogenicity test of rasH2 mice under the conditions of
      the present study.

PMID- 17202758
TI  - Genomic cluster and network analysis for predictive screening for hepatotoxicity.
AB  - The present study was undertaken to estimate the usefulness of genomic approaches
      to predict hepatotoxicity. Male rats were treated with acetaminophen (APAP),
      carbon tetrachloride (CCL), amiodarone (AD) or tetracycline (TC) at toxic doses.
      Their livers were extracted 6 or 24 hr after the dosings and were used for
      subsequent examinations. At 6 hr there were no histological changes noted in any
      of the groups except for the CCL group, but at 24 hr, such changes were noted in
      all but the AD group. Regarding genomic analysis, we performed hierarchical
      cluster analysis using S-plus software. The individual microarray data were
      clearly classified into 5 treatment-related clusters at 24 hr as well as at 6 hr,
      even though no morphological changes were noted at 6 hr. In the gene expression
      analysis using GeneSpring, transcription factor and oxidative stress- and lipid
      metabolism-related genes were markedly affected in all treatment groups at both
      time points when compared with the corresponding control values. Finally, we
      investigated gene networks in the above-affected genes by using Ingenuity Pathway
      Analysis software. Down-regulation of lipid metabolism-related genes regulated by
      SREBP1 was observed in all treatment groups at both time points, and up
      regulation of oxidative stress-related genes regulated by Nrf2 was observed in
      the APAP and CCL treatment groups. From the above findings, for the application
      of genomic approaches to predict hepatotoxicity, we considered that cluster
      analysis for classification and early prediction of hepatotoxicity and network
      analysis for investigation of toxicological biomarkers would be useful.

PMID- 17202759
TI  - Utilization of a one-dimensional score for surveying chemical-induced changes in
      expression levels of multiple biomarker gene sets using a large-scale
      toxicogenomics database.
AB  - A large-scale toxicogenomcis database has now been constructed in the
      Toxicogenomics Project in Japan (TGP). To facilitate the analytical procedures
      for such large-scale microarray data, we developed a simple one-dimensional
      score, named TGP1 which expresses the trend of the changes in expression of
      biomarker genes as a whole. To evaluate the usefulness of the TGP1 score,
      microarray data of rat liver and rat hepatocytes deposited in the TGP database
      were scored for three biomarker gene sets, i.e., carcinogenesis-related,
      PPARalpha-regulated and glutathione depletion-related gene sets. The TGP1 scoring
      system gave reasonable results, i.e., the scores for carcinogenesis-related genes
      were high in omeprazole-, chlorpromazine-, hexachlorobenzene-, sulfasalazine- and
      Wy-14,643-treated rat livers, that for PPARalpha-regulated genes were high in
      clofibrate-, Wy-14,643-, gemfibrozil-, benzbromarone- and aspirin-treated rat
      livers as well as rat hepatocytes, and for glutathione deficiency-related genes
      were high in omeprazole-, bromobenzene-, acetaminophen- and coumarin-treated rat
      liver. We concluded that the TGP1 score is useful for surveying the expression
      changes in multiple biomarker gene sets for a large-scale toxicogenomics
      database, which would reduce the time of doing conventional multivariate
      statistical analysis. In addition, the TGP1 score can be applied to screening of
      compatible biomarker gene sets between rat liver and rat hepatocytes, like
      PPARalpha-regulated gene sets, which will allow us to develop an appropriate in
      vitro system for drug safety assessment in vivo.

PMID- 17202760
TI  - Comparison of gene expression profiles among papilla, medulla and cortex in rat
      kidney.
AB  - The aim of this study was to compare gene expression profiles in the different
      kidney regions as the basis for toxicogenomics. Rat kidney was separated into
      papilla, medulla and cortex, and total RNA was isolated from these and from the
      whole slice. Gene expression profiling was performed using Affymetrix Rat Genome
      230 2.0 Array. When global normalization was applied, the expression of beta
      actin or GAPDH varied among the regions. It was considered that such a comparison
      could not be made, especially between papilla and other portions, since the
      production of total mRNA in the former was relatively low. In fact, ANOVA was
      performed on the gene expression values with global normalization in papilla,
      medulla, cortex, and whole slice, and the numbers of genes appeared to be the
      highest in papilla. It was also observed that many genes showed their maximum or
      minimum in the whole slice, which was theoretically impossible. To overcome the
      problems associated with global normalization, the "percellome" normalization (a
      way to obtain the values directly related to the copies of mRNA per cell) was
      employed to compare the regions. In applying this procedure, probe sets with
      regional difference in expression were efficiently extracted by ANOVA. When they
      were sorted by the fold difference to other regions, the higher rank was occupied
      by genes characteristic of the functions of kidney, i.e., channels, transporters
      and metabolic enzymes. Some of them were consistent with the literature and were
      related to pathophysiological phenomena. Comprehensive comparison of data of gene
      expression in the renal anatomical area will greatly enhance studies of the
      physiological function and mechanism of toxicity in kidney.

PMID- 17202762
TI  - Gene expression profile in liver of differing ages of rats after single oral
      administration of acetaminophen.
AB  - In order to verify the influence of the rat age on hepatotoxicity, male Sprague
      Dawley rats of 6 (young) and 12 (adult) weeks of age were orally administered
      acetaminophen (APAP), isoniazid (INH), or carbon tetrachloride (CCl4). Liver
      samples were obtained in a time-course manner, and changes in gene expression
      examined by an Affymetrix GeneChip. APAP caused more prominent hepatic injury
      with respect to pathology and blood biochemistry in adults than in young rats,
      whereas no obvious age-related differences were observed in INH- or CCl4-treated
      rats. Comparing gene expression in control rats, CYP3A13 was higher and GSTY2c
      was lower in adults, suggesting that production of the active metabolite of APAP
      is higher and its detoxification is lower in adults. The total amount of
      glutathione and total SH in rat liver was found to be higher in adult rats
      whereas the extent of its reduction by APAP was larger in adults. A detailed
      analysis of genes showing age-related differences revealed that some of them were
      different not in their extent but in their time course, i.e., the stress
      responses occurred earlier in the young than in the adult, resulting in a
      difference at 24 hr after dosing. These results suggest that the age-related
      difference in toxicity would be attributed to a higher expression of CYP3A13,
      producing the active metabolite of APAP as well as the lower expression of the
      detoxification enzyme, GSTY2c, in adult rats. Furthermore, these differences
      affect the time course of APAP toxicity. The present study clearly depicts the
      advantage of the multi-time, multi-dose protocol employed in our project for
      analyzing the mechanism of toxicity by gene expression profiling.

PMID- 17202761
TI  - Profiling of gene expression in rat liver and rat primary cultured hepatocytes
      treated with peroxisome proliferators.
AB  - The Toxicogenomics project has been constructing a large-scale database of about
      150 compounds exposed to rat (single dose, 3, 6, 9, 24 hrs and repeated dose for
      3, 7, 14 28 days with 3 dose levels) and rat hepatocytes (2, 8, 24 hr with 3
      concentrations) and data of transcriptome in liver using GeneChip, and the
      related toxicological measures are being accumulated. In the present study, the
      data of three ligands of peroxisome proliferator activated receptor alpha
      (PPARalpha), i.e., clofibrate, WY-14643 and gemfibrozil in our database were
      analyzed. Many of the beta-oxidation-related genes were commonly induced in vivo
      and in vitro, whereas expression changes in genes related to cell proliferation,
      apoptosis, were detected in vivo (single and repeated dose) but not in vitro.
      Changes in those related to the immune response, coagulation and the stress
      response were also detectable exclusively in vivo. Using the genes mobilized in
      two or three PPARalpha agonists, hierarchical clustering was performed on 32
      compounds stored in our database. In the profiling of an in vivo single dose,
      benzbromarone and aspirin were located in the same cluster of the three PPARalpha
      agonists. The clustering of in vitro data revealed that benzbromarone, three
      NSAIDs (aspirin, indomethacin and diclofenac sodium) and valproic acid belonged
      to the same cluster of PPARalpha agonists, supporting the reports that
      benzbromarone,valproic acid and some NSAIDs were reported to be PPARalpha
      agonists. Using the genes commonly up-regulated both in vivo and in vitro,
      principal component analysis was performed in 32 compounds, and principal
      component 1 was found to be the convenient parameter to extract PPARalpha agonist
      like compounds from the database.

PMID- 17202763
TI  - Evaluation of methods for duration of preservation of RNA quality in rat liver
      used for transcriptome analysis.
AB  - In The Toxicogenomics Project, about 150 chemicals are administered to rats, and
      gene expression in the liver analyzed by Affymetrix GeneChip and stored in the
      database. As the quality of RNA greatly influences the accuracy of gene
      expression data, conditions of the storage of the sample are very important.
      Recently, an RNA stabilization solution, RNAlater, has become commercially
      available. In this study, the new storage method was compared with the
      traditional storage method (stored in freezer or liquid nitrogen) under various
      conditions by looking at the degradation of RNA assessed by its total yield,
      OD260/280 ratio, 28S/18S ratio, and quantity of beta-actin. It was confirmed that
      RNAlater preserved the liver tissue sample by maintaining the quality of RNA for
      one year (in liquid N(2) or -80 degrees C), for 3 days (4 degrees C), or for 2 hr
      (room temperature) without degradation of RNA. Quality of RNA samples dissolved
      in buffer RLT and stored at -20 degrees C tended to decrease, but samples stored
      at -80 degrees C were almost equivalent to those stored in liquid nitrogen. In
      conclusion, we recommend the following procedure for preservation of liver tissue
      for extraction of RNA: 1) tissues removed should be put into chilled RNAlater as
      soon as possible; 2) samples in RNAlater must be stored overnight or longer at 4
      degrees C and can be left for as long as 2 weeks without freezing; 3) samples in
      RNAlater can be stored for at least one year under less than -20 degrees C and 4)
      samples dissolved in buffer RLT can be preserved at least for one year under -80
      degrees C.

PMID- 17202764
TI  - Transplacental disposition and teratogenic effects of chlorpyrifos in rats.
AB  - Rats were orally fed with different doses viz. 9.6, 12 and 15 mg/kg/d from GD 0
      20 and examined for evidence of fetotoxicity and teratogenecity to evaluate the
      potential effects of technical chlorpyrifos (97%). Fetotoxic effects were not
      observed at tested dose levels as evidenced by number of implantations, number of
      corpora lutea and live fetuses/dam, but significant alterations were noted in
      percent delta resorption and fetal weight. There were no major malformations, but
      some minor anomalies such as reduced parietal ossification and absence of
      phalanges found significant in high dose were not considered as compound-related
      effects. On the other hand the accumulation of chlorpyrifos residue in dams was
      more in brain (0.0328 micro g/g) than in liver (0.0071 micro g/g).The level of
      residue in fetuses was in the following order : liver (0.0531 micro g/g) > brain
      (0.0364 micro g/g) >placenta (0.040 micro g/g) > amniotic fluid (0.0010 micro
      g/g). Although, the total residue was higher in fetuses (0.0447 micro g/g) than
      in dams (0.0120 micro g/g), the absence of abnormalities in fetal gross
      morphology, visceral and skeleton suggest that technical chlorpyrifos at tested
      dose levels is non-teratogenic in rats.

PMID- 17202765
TI  - Characteristics of home cage locomotion in cynomolgus monkeys.
AB  - The profiles of home cage locomotor activity and its rhythmicity were
      investigated using a camera system for 4 consecutive days in cynomolgus monkeys.
      Nine male and nine female cynomolgus monkeys were used in this study, and were
      found to have the same profile in nocturnal behavior in that they were mostly
      inactive during the night. The locomotor activity of both sexes showed a normal
      activity and inactivity rhythm, which had an inverse relationship between normal
      activity and inactivity, showing a fluctuation profile of being higher in the
      light cycle and lower in the dark cycle. The four-day locomotion time of the
      females was higher than that of the males in the dark period. The females also
      showed a higher locomotion count and D/L ratio in the dark period than the males
      during the 4 consecutive days. These findings indicate that the females have
      greater locomotor activity in the dark period than that of the males. The present
      findings may serve as useful basic data for the behavioral assessment of overall
      animal movements in toxicological studies using monkeys.

PMID- 17202766
TI  - DNA microarray analysis of transcriptional responses of human neuroblastoma IMR
      32 cells to methylmercury.
AB  - We used DNA microarrays to monitor the transcriptional responses of IMR-32
      neuroblastoma cells to methylmercury. Methylmercury increased levels of
      expression of seven genes, including genes for ETV5 and ID4, and reduced those of
      two genes.

PMID- 17202767
TI  - Polymorphisms of the factor VII gene associated with the low activities of
      vitamin K-dependent coagulation factors in one-month-old infants.
AB  - Despite administration of vitamin K (VK), some infants show lower activity of VK
      dependent coagulation factors and they could develop intracranial hemorrhage. For
      preventing VK deficiency bleeding (VKDB) in infants, oral administration of VK
      and a screening test for VK deficiency are carried out in Japan. For the
      screening, the total activity of VK-dependent coagulation factors is measured
      using a commercial product, Normotest. This study was undertaken to clarify the
      importance of the following genetic and environmental factors on the coagulation
      status in one-month-old infants: two polymorphisms in the factor VII gene, 
      323P0/10 (a 10-bp insertion in the promoter region at position -323) and R353Q
      (the replacement of arginine [R] with glutamine [Q] at residue 353) and sex, age,
      gestational age, birth weight, and feeding regimen. Two hundred Japanese infants
      (34.6 +/- 4.0 days old) were screened for VK-dependent coagulation activity with
      Normotest and were genotyped for the two polymorphisms. Among the subjects
      screened, 18 infants (9%) carried the P10 allele and 26 (13%) carried the R353Q
      allele. Multiple regression analysis showed that the 10-bp inserted (P10) allele
      or the Q allele was associated with the lower coagulation activities. The
      coagulation activities for the R/Q genotype were significantly lower than those
      for the R/R genotype and those for the P0/P10 genotype were significantly lower
      than those for the P0/P0 genotype. Therefore, infants who carry the P10 allele or
      the Q allele show lower activity of VK-dependent coagulation factors. These
      infants may have a higher risk of VKDB manifestation.

PMID- 17202768
TI  - The usefulness of day-service in maintaining general nutritional status in
      elderly Japanese: a longitudinal study.
AB  - Day-service, commuting service for elderly people requiring care at home, is one
      healthcare option in Japan. To date, however, there exist no studies that have
      examined the effects of day-service use on health outcomes in Japan. The
      objective of the present longitudinal study was to determine whether there is an
      association between day-service use and various physical and mental health
      outcomes in elderly people requiring care. The subjects were 61 elderly persons
      who required between 25 and 49 min of assistance per day and used long-term care
      insurance. Measurements included demographic characteristics, activities of daily
      living, frequency of day-service use, body weight, height, grip strength, thigh
      muscle volume, degree of depression (Geriatric Depression Scale), the mini-mental
      state examination, and serum albumin and blood hemoglobin levels in the baseline
      and follow-up surveys two years later. In the day-service user group, the mean
      changes in serum albumin concentrations using day-service once, twice and three <
      or = times/week were -0.2, -0.3, and 0 g/dl, respectively, and the mean changes
      in blood hemoglobin were -0.7, -0.5, and 0.2 g/dl, respectively. The two-year
      change in serum albumin concentrations was less (p = 0.024) in subjects using day
      service "three < or = times" (0 g/dl) than "twice" (-0.3 g/dl). The two-year
      change in blood hemoglobin was also less (p = 0.043) in subjects using day
      service "three < or = times" (0.2 g/dl) than "twice" (-0.5 g/dl). The present
      study has shown that frequent use of day-service is useful in maintaining general
      nutritional status in elderly people.

PMID- 17202769
TI  - Increased nitrosative and oxidative stress in platelets of migraine patients.
AB  - The molecular mechanisms of migraine have not been fully clarified yet. Increased
      nitrosative and oxidative stress may be associated with migraine attacks.
      Platelets may play an important role in migraine patients and they can reflect
      the lability of tissues to nitrosative/oxidative stress. In the present study, we
      aimed to determine the levels of nitrosative and oxidative stress markers in
      platelets of migraine patients during headache-free and attack periods. A total
      of 56 subjects (22 migraine without aura, 14 migraine with aura, and 20 age- and
      sex-matched healthy controls) were included in the study and nitric oxide (NO)
      metabolites, malondialdehyde (MDA), and thiol (SH) groups were measured in
      platelets. During migraine attacks, platelet levels of nitrate, nitrite and MDA
      were significantly higher in migraineurs than these in control subjects (p =
      0.042, p = 0.005 and p = 0.042, respectively). By contrast, during headache-free
      period, no statistically significant differences were found in the platelet
      levels of nitrate, nitrite and MDA between migraineurs and controls (p > 0.05),
      although the marginal increases were detected in migraineurs. These results
      suggest that increased biomarkers of nitrosative and oxidative stress in
      platelets may be important in migraine patients, especially during attacks;
      increase of NO metabolites in platelets during attacks supports the opinion that
      NO may play a modulatory role in biological processes particularly by
      vasodilatation in migraine attacks. Therefore, MDA and NO metabolites may serve
      as useful markers to show the increased vulnerability to nitrosative and
      oxidative stress in migraine patients.

PMID- 17202770
TI  - Augmenting effect of serotonin on the voltage-dependent Ca2+ current and
      subsequently activated K+ current in Aplysia neurons.
AB  - Receptor-induced activation of protein kinase C (PKC) plays an important role in
      modulation of various types of ionic channels in neurons. For example, PKC causes
      facilitation or long-lasting activation of certain ionic channels involved in
      spike firing after the receptor stimulation. We investigated the effect of
      serotonin (5-HT) on the voltage-dependent Ca(2+) channels in RB and RC neurons of
      Aplysia ganglia under voltage clamp. An outward current response was induced by
      voltage change of the cell membrane from -60 mV to +10 mV. Application of 5-HT
      significantly augmented the outward current response to the voltage change. Both
      the outward current and the augmenting effect of 5-HT markedly decreased when
      examined in either Ca(2+)-free, 10 mM tetraethylammonium, or 0.3 mM Cd(2+)
      solution, indicating the current to be Ca(2+)-activated K(+) current produced by
      Ca(2+) entry. Intracellular application of either guanosine 5'-O-(2
      thiodiphosphate) or cholera toxin (CTX), reagents for G-proteins, irreversibly
      blocked the augmenting effect of 5-HT. Application of phorbol dibutylate (PDBu),
      an activator of PKC, augmented the outward current and the effect of 5-HT was
      occluded after PDBu application. Staurosporine, a specific inhibitor of PKC,
      markedly suppressed the augmenting effects of both 5-HT and PDBu on the outward
      current. However, either 5-HT or PDBu did not augment the Ca(2+)-activated K(+)
      current induced by intracellular injection of Ca(2+) but rather depressed it.
      These results suggest that stimulation of 5-HT receptor may activate a novel type
      of CTX-sensitive G-protein and subsequent PKC, and that phosphorylation of
      voltage-dependent Ca(2+) channels may result in the increase in Ca(2+) entry and
      subsequent Ca(2+)-activated K(+) current. The mechanism may contribute to retain
      the long-lasting activation without broadening of the spike width during the
      excitatory response to 5-HT in these neurons.

PMID- 17202771
TI  - Cardiac resynchronization improves coronary blood flow.
AB  - Asynchronous ventricular activation, induced by left bundle branch block, is
      known to have deleterious effects on the systolic and diastolic functions of the
      left ventricle (LV). Cardiac resynchronization therapy (CRT) has been proposed as
      a complementary method to improve the LV systolic performance by restoring the
      synchronized contraction patterns in patients with advanced heart failure and
      left bundle branch block. However, the effect of CRT on myocardial blood flow is
      not well established. In the present study, we therefore examined the coronary
      blood flow in 20 patients with idiopathic dilated cardiomyopathy, implanted with
      a biventricular pacemaker according to the established CRT criteria. Color
      Doppler settings were adjusted for the optimal coronary flow imaging, and
      coronary flow velocities were obtained in all patients. Typical diastolic
      predominant phasic Doppler spectrum of the distal left anterior descending
      coronary artery (LAD) was recorded. Conventional echocardiographic variables,
      peak values of the diastolic and systolic LAD velocities, and the velocity time
      integrals were measured for three or five consecutive beats during CRT with
      pacemaker on and off. Successful CRT with biventricular pacing increased coronary
      blood flow velocities of the distal LAD in addition to its well-known benefits on
      the systolic and diastolic LV performance in patients with significant
      dyssynchrony. CRT decreased duration of mitral regurgitation and increased
      diastolic filling time. Peak diastolic velocities and velocity time integral of
      the distal LAD were increased significantly. In conclusion, successful CRT with
      biventricular pacing improves coronary blood flow velocities of the distal LAD.

PMID- 17202772
TI  - Nursing students' willingness to use complementary and alternative therapies for
      cancer patients: Istanbul survey.
AB  - It is important for student nurses to be knowledgeable of the complementary and
      alternative therapies and to provide accurate information to both cancer patients
      and other health care professionals. This study examined the nursing students'
      willingness to use these therapies, availability of sources of information, use
      of the therapies for self care, opinions about the integration of these therapies
      into nursing curriculum, and analyzed the differences among the responses. A self
      administered questionnaire was offered to 640 nursing students in Istanbul,
      descriptive statistics were used, and comparisons among responses were made with
      chi-square test. Willingness to use for cancer patients was highest for
      nutritional therapy (76.1%), breathing therapies (74.5%), and massage and
      manipulation-Tui Na, in which pressure and touch are applied to the body (71.9%).
      Use of information sources was highest for nutritional therapy (75.6%), breathing
      therapies (71.9%), and massage and manipulation-Tui Na (62.3%). Over half of the
      nursing students used music therapy (54.2%), and massage and manipulation-Tui Na
      (53.6%) for self-care. Breathing therapies (87.2%) were the most desired therapy
      chosen to be included in nursing curriculum. The statistically significant
      differences were found among the responses related to use five therapies for care
      and related to desired three therapies to be included in nursing curriculum.
      Although students had not previously been exposed to these therapies use with
      oncology patients, many of students expressed a desire to integrate therapies
      learning into nursing curriculum. The more student nurses document high risk
      patients, the more effective strategies will be developed by other health care
      professionals.

PMID- 17202773
TI  - Strain-specific pulmonary defense achieved after repeated airway immunizations
      with non-typeable haemophilus influenzae in a mouse model.
AB  - Strain-specific immune responses may play a critical role in the acute
      exacerbation of chronic obstructive pulmonary disease (COPD) caused by
      Haemophilus influenzae (NTHi), and the outer membrane protein P2 is one of
      surface antigens of NTHi, which may contribute to the strain-specific protective
      immunity. We examined whether repeated airway immunizations with killed-NTHi
      strains bearing different P2 molecules were capable of inducing protective
      immunity against homologous or heterologous strains in the lungs of a mouse
      model. Three different strains of NTHi were used in this study. Three serial
      intratracheal (IT) immunizations of a single strain or three different strains of
      NTHi led to the production of cross-reactive immunoglobulins G and A in
      bronchoalveolar lavage fluids. Three serial IT immunizations with a single strain
      enhanced the bacterial clearance of the homologous strain in the lungs, but no
      enhancement of bacterial clearance was found with three serial IT immunizations
      of heterologous strains. The enhancement in bacterial clearance, therefore,
      appears to be primarily strain-specific. Enhanced bacterial clearance of a
      heterologous strain was also found after three serial IT immunizations of a
      single strain among two of the three strains employed for bacterial challenge.
      These findings suggest that P2 molecules and surface antigens other than P2 are
      involved in the development of pulmonary defense against NTHi in mice. Our data
      may explain, in part, why patients with COPD experience recurrent NTHi
      infections.

PMID- 17202775
TI  - Neuro-fuzzy technology as a predictor of parathyroid hormone level in
      hemodialysis patients.
AB  - Measuring the plasma parathyroid hormone (PTH) concentration is crucial to
      evaluate renal bone disease in patients with renal failure. Although frequent
      measurement is needed to avoid inadequate prescription of phosphate binders and
      vitamin D preparations, artificial intelligence can repeatedly perform the
      forecasting tasks and may be a satisfactory substitute for laboratory tests.
      Neuro-fuzzy technology represents a promising forecasting application in clinical
      medicine. We therefore constructed a coactive neuro-fuzzy inference system
      (CANFIS) to predict plasma PTH concentrations in hemodialysis patients. The
      CANFIS was constructed with clinical parameters (patient age, plasma albumin,
      calcium, phosphorus, alkaline phosphatase, and calcium-phosphorus product) from a
      cohort of hemodialysis patients, and plasma PTH concentration measured by
      radioimmunoassay (RIA) was the supervised outcome. The accuracy of the CANFIS was
      prospectively compared with RIA in another hospital. Plasma PTH concentrations
      measured by RIA and predicted by CANFIS were 179.04 +/- 38.18 ng/l and 179.34 +/-
      37.76 ng/l, respectively (p = 0.15). The CANFIS was able to precisely estimate
      plasma PTH concentrations in hemodialysis patients. These results suggest that
      the neuro-fuzzy technology, based on limited clinical parameters, is an excellent
      alternative to RIA for accurately predicting plasma PTH concentration in
      hemodialysis patients.

PMID- 17202774
TI  - The single-step multiplex reverse transcription- polymerase chain reaction assay
      for detecting H5 and H7 avian influenza A viruses.
AB  - Avian influenza (AI) A virus subtypes H5 and H7 cause severe disease in domestic
      poultry, including chickens and turkeys. Moreover, H5 and H7 AI A viruses can
      cross the species barrier from poultry to humans. In the present study, we have
      developed a single-step multiplex reverse transcription-polymerase chain reaction
      assay (RT-PCR) for detecting H5 and H7 AI A viruses. This assay was applied to
      the poultry isolates with the aim of establishing a surveillance method to
      monitor possible transmission to humans. Two subtype-specific primer sets capable
      of producing PCR products of 157 and 326 base pairs corresponding to AI A virus
      H5 and H7 subtypes, respectively, were utilized in a one-step and one-tube
      reaction. The single-step multiplex RT-PCR assay developed in this study was
      found to be specific for detecting H5 and H7 AI A viruses. No specific
      amplification bands were detected with total nucleic acids extracted from other
      influenza hemagglutinin subtypes and other viral pathogens. The sensitivity of
      this assay was about 10(3) RNA copies/microl. In conclusion, this novel single
      step multiplex RT-PCR is a simple assay with high potential for rapid, specific
      and cost effective laboratory diagnosis of H5 and H7 AI A virus isolates from
      clinical specimens of poultry.

PMID- 17202776
TI  - Insufficiency fracture of the sternum simulating myocardial infarction: case
      report and review of the literature.
AB  - Insufficiency fracture is a type of stress fracture that occurs when stress is
      applied to the bone with less than the normal elastic resistance, as in
      osteoporosis. Insufficiency fracture of the sternum is rare among all kinds of
      fractures. We describe two cases with insufficiency fractures of the sternum
      secondary to osteoporosis and thoracic kyphotic deformity. Both of the present
      cases, a 76-year-old woman and a 65-year-old woman, presented with severe
      anterior chest pain simulating myocardial infarction. However, cardiopulmonary
      examinations including chest radiographs, electrocardiograms, and laboratory
      tests were normal. Lateral radiographs of the sternum in both patients showed
      insufficiency fractures of the sternum. Conservative treatment with rib
      bandaging/bracing and analgesics relieved their symptoms. Clinical behavior, type
      of sternal insufficiency fractures, and mechanism of the fracture are reviewed
      from perusal of the literature. We emphasize that sternal insufficiency fracture
      should be considered in the differential diagnosis of acute chest pain in the
      elderly along with myocardial infarction or pulmonary embolism.

PMID- 17202779
TI  - [Novel functions and regulatory mechanisms of G protein-coupled receptors].

PMID- 17202777
TI  - Cerebral folate deficiency and folinic acid treatment in hypomyelination with
      atrophy of the basal ganglia and cerebellum (H-ABC) syndrome.

PMID- 17202780
TI  - [Regulation of G protein-coupled receptor function by its binding proteins].
AB  - G protein-coupled receptors (GPCRs) are seven transmembrane receptors with an N
      terminus in the extracellular region and C-terminus in the intracellular region.
      When an agonist binds to a GPCR, a signal is transduced into a cell through the
      activation of trimeric G proteins. Recently, it has been shown that the
      activities of GPCRs are regulated by multiple mechanisms. One of the mechanisms
      is regulation through the binding proteins to the carboxy (C)-terminus of GPCRs.
      In the present study, the binding partners for the C-terminus of the parathyroid
      hormone receptor (PTHR) and thromboxane A(2) receptor (TP) were searched for
      using yeast two-hybrid screening, and the functions of these proteins were
      investigated. We identified t-complex testis expressed-1 (Tctex-1) and 4.1G as
      associated proteins for the PTHR. Tctex-1 is one of the light chains of
      cytoplasmic dynein, which is a motor protein across microtubles. We found that
      Tctex-1 was involved in agonist-induced internalization of the PTHR. 4.1G, a
      cytoskeletal protein, facilitated the cell surface localization of the PTHR and
      augmented PHTR-mediated signal transduction. TPs consists of two splicing
      variants, TPalpha and TPbeta. As a result of yeast two-hybrid screening, two
      proteasomal proteins, proteasome activator PA28gamma and proteasome subunit
      alpha7, were identified as direct interacting proteins for TPbeta. TPbeta has a
      tendency to be retained in the intracellular compartment, probably due to its
      binding to proteasomes. We also demonstrated that TPalpha and TPbeta formed
      heterodimers, and the signal transduction through TPalpha was reduced by the
      formation of heterodimers. In conclusion, the proteins bound to GPCRs may
      regulate the intracellular traffic of GPCRs.

PMID- 17202781
TI  - [Role of therapeutics for allergic diseases in targeting histamine H1 receptor
      gene expression].
AB  - Histamine H(1) receptors are down-regulated as one step in receptor
      desensitization. Five phosphorylation sites of the H(1) receptor seem to play a
      key role in receptor down-regulation. In contrast, an increase in the H(1)
      receptor expression level following its mRNA elevation was found in the nasal
      mucosa in hypersensitivity model rats. Up-regulation of the H(1) receptor was
      induced by the direct stimulation of the H(1) receptor. H(1) receptor up
      regulation was suppressed by pretreatment with antiallergic agents.

PMID- 17202783
TI  - [Antibody engineering for advanced molecular recognition].

PMID- 17202782
TI  - [Role of lipid rafts in trimeric G protein-mediated signal transduction].
AB  - Lipid rafts and caveolae are microdomains in the cell membranes, which contain
      cholesterol, glycolipids, and sphingomyelin. While caveolae are relatively stable
      because caveolin, an integral protein, supports the structure, lipid rafts are
      considered to be unstable, being dynamically produced and degraded. Recent
      studies have reported that lipid rafts contain many signaling molecules, such as
      glycosylphosphatidylinositol-anchored proteins, acylated proteins, G-protein
      coupled receptors (GPCRs), trimeric and small G-proteins and their effectors,
      suggesting that the lipid rafts have an important role in receptor-mediated
      signal transduction. Therefore drugs that modify the composition of lipid rafts
      might influence the efficacy of cellular signal transduction. In this review, we
      demonstrate the role of lipid rafts in GPCR-G-protein signaling and also present
      our recent results showing that the wasp toxin mastoparan modifies G(q/11)
      mediated phospholipase C activation through the interaction with gangliosides in
      lipid rafts.

PMID- 17202784
TI  - [Development of diagnostically and therapeutically useful human antibody
      medicines by phage display system].
AB  - Phage display has been utilized for making recombinant antibody fragments (Fab or
      single chain Fv) of human, mouse, or other origins. After construction of an
      antibody combinatorial library, antigen-specific recombinant antibody fragments
      can be easily isolated by biopanning of the phage library displaying antibody
      fragment fused with viral coat protein III against antigen proteins, antigen
      expressing live cells, or fixed cells. Using this technique, a variety of human
      recombinant antibody fragments can be retrieved from bone marrow cells, lymph
      node cells, or peripheral blood cells of patients with infectious diseases,
      autoimmune diseases, and cancer. To develop diagnostically and therapeutically
      useful human antibody medicines, we should first select recombinant antibody
      fragments not only with antigen-binding activity but also with bioactivity such
      as virus or toxin neutralization, or tumor-specific cytotoxicity. To achieve this
      goal, several steps in antibody phage display may be improved: 1) a larger
      library should be constructed for possible isolation of minor populations present
      in the repertoire; 2) the biopanning procedure should be improved for isolation
      of antibody fragments reactive with immunologically minor epitopes; 3) the
      screening procedure should be based on the measurement of the bioactivity as well
      as the antigen-binding activity; 4) if necessary, the affinity and specificity of
      selected antibody fragments should be improved. In this review, I discuss how to
      isolate clinically useful recombinant antibody fragments efficiently using a
      phage display system introducing our achievements.

PMID- 17202785
TI  - [Antibody engineering-based approach for hapten immunometric assays with high
      sensitivity].
AB  - The trace characterization of physiologically active substances with low
      molecular weight (e.g., steroids, catecholamines, prostaglandins, and
      oligopeptides), which are classified as "haptens", is an important subject in
      clinical analysis, and competitive immunoassays have conventionally been used for
      this purpose. However, the subfemtomole-range determination of haptens is very
      difficult, as the sensitivity of competitive immunoassays is essentially limited
      by the affinity of the anti-hapten antibodies that barely reaches the range of
      10(11) (l/mol) as the affinity constant (K(a)). Although a noncompetitive
      "immunometric assay" format, the two-site immunometric assay (sandwich
      immunoassay), enables even subattomole-range measurements of macromolecules such
      as proteins, this principle can not be directly applied to haptens, as their low
      molecular mass prohibits simultaneous binding by two antibody molecules. To
      overcome such limitations, we are required either to create artificial antibodies
      showing ultrahigh affinity to haptens by protein engineering of antibody
      molecules ("antibody engineering") or establishment of novel immunometric assay
      formats applicable to haptens. This review surveys the background and recent
      approach for subfemtomole-range determination of haptens using novel immunometric
      assay methods. Our studies for the development of hapten immunometric assays are
      also described.

PMID- 17202786
TI  - [Sensitive noncompetitive measurement of small molecules by open sandwich
      immunoassay].
AB  - Proteins having multiple epitopes can be usually measured with sandwich ELISA
      employing two kinds of antibodies, which permits high sensitivity as well as a
      wide working range of more than three orders of magnitude. On the other hand, so
      called monovalent antigens with MW less than 1000 are not susceptible to sandwich
      assays due to their small size and have almost always been measured in
      competitive assays. However, while a competitive assay needs only one antibody
      due to the principle of ratiometric measurement, optimization of the reaction
      conditions is necessary to attain suitable sensitivity and working range, which
      are often inferior to those of sandwich assays. As an alternative immunoassay for
      small antigens, here we propose a noncompetitive "open sandwich" immunoassay,
      which is based on the principle of stabilization of the antibody variable region
      Fv upon binding with antigen. Using ELISA to detect labeled V(H) fragments bound
      to immobilized V(L) in the presence of sample in microplate wells, various small
      molecules with MW around 200-300 can be measured with a superior detection limit
      and working range compared with those achieved with the corresponding competitive
      assays. The results indicate a common antigen recognition mode of anti-hapten
      antibody and wide applicability of the assay to the sensitive and handy analysis
      of low molecular-weight substances in areas such as environmental analysis and
      clinical diagnostics.

PMID- 17202787
TI  - [ADLib system for rapid and flexible design of monoclonal antibodies].
AB  - Monoclonal antibodies (MAbs) have been utilized as research tools, as diagnostic
      reagents, and for antibody medicine. The preparation of MAbs involves laborious
      processes and normally takes months. Here we describe an ex vivo B cell-based
      antibody display system called the ADLib (Autonomously Diversifying Library)
      system, which enables us to select chicken B cell clones producing antibody
      against antigens of interest in a couple of weeks. The ADLib system is applicable
      to self- or highly conserved antigens, polysaccharide chains, peptides, and
      haptens.

PMID- 17202788
TI  - [Directed evolution of antibody molecules in phage-displayed combinatorial
      libraries].
AB  - Advances in methods for conformational prediction, structural analysis and site
      directed mutagenesis of proteins and peptides have contributed to the
      understanding of their structure and function. However, with the exception of a
      few successes, the generation of practical functional molecules solely by
      rational design remains a difficult challenge. The aim of our study is to
      investigate molecular design relying on evolutionary processes, called as
      "directed evolution", to generate a novel class of biofunctional molecules. This
      evolutionary approach consists of three steps; 1) constructions of
      protein/peptide libraries based on structural information, 2) expressions of the
      libraries on phage particles, and 3) selections with investigator-imposed
      selective pressures. In this work, we study on directed evolution with antibody
      libraries. We have succeeded in generating highly active catalytic antibodies in
      phage-displayed antibody (Fab) libraries. To evolve catalytic antibodies toward
      higher catalytic activity, we have mimicked an enzyme-evolutional process, in
      which an enzyme has evolved their ability to use binding energies for catalysis
      by increasing the affinity for the transition state of a reaction and decreasing
      the affinity for the ground state. Thus, phage-displayed libraries derived from
      an original catalytic antibody were selected against a newly-devised TSA, which
      was programmed to optimize the differential affinity for the transition state
      relative to the ground state, to provide variants with improved reaction rates
      (k(cat)). The in vitro evolution has great potential for generating novel
      catalysts as well as for providing opportunities to examine the evolutionary
      dynamics of enzymes.

PMID- 17202789
TI  - [Virtual screening based on protein-ligand interactions].

PMID- 17202790
TI  - [Interface between bioinformatics and docking study].
AB  - We describe the prospects of bioinformatics for drug discovery and discuss the
      current status, problems, and future direction of the interface between
      bioinformatics and docking studies. We also describe our recent work on sequence
      and structure analysis using the guanidino-modifying enzymes superfamily as a
      good example.

PMID- 17202791
TI  - [Docking method for drug discovery].
AB  - The effective integration of detailed structural information with computational
      chemistry, medicinal chemistry, and informatics transforms the dream of virtual
      screening into reality. One of the most important technologies essential for
      virtual screening is an effective docking method to find molecules that
      efficaciously interact with their target molecules. Since an efficient docking
      method can be a powerful tool for virtual screening, many different approaches to
      solving docking problems have been proposed. Docking problems have not yet been
      solved and none of the currently available programs are perfect in predicting all
      possible scenarios. Despite the limits and imperfections of the methodology,
      currently available docking methods are very useful for drug discovery. The basic
      principles and limits of docking methods together with matters for attention in
      applying the methods are described in this paper.

PMID- 17202793
TI  - [Genetic approaches for the elucidation of disease development mechanisms and the
      creation of innovative medicines].

PMID- 17202792
TI  - [Receptor-ligand docking simulation for membrane proteins].
AB  - Protein structure-based molecular design using the computational techniques of
      protein structure prediction, ligand docking, and virtual screening is an
      integral part of drug discovery for limiting the application of the structure
      based approach to target proteins such as G-protein-coupled receptors (GPCRs).
      GPCRs play an important role in living organisms and are of major interest to the
      pharmaceutical industry. However, structural data on ligand-binding forms for
      GPCRs from experiments to elucidate structural templates for docking simulations
      are lacking due to the difficulties associated with crystallization and
      crystallography. Therefore structural prediction of GPCRs in the ligand-bound
      state using computational methods has been introduced, but the prediction of
      ligand conformation onto target GPCRs is still constructed manually by human
      experts. We developed a molecular modeling technique for the prediction of ligand
      receptor binding using comparative ligand-binding analysis (CoLBA) that not only
      considers interaction energy but also the similarity of interaction profiles
      among ligands. The advantage of CoLBA is that it can facilitate intuitive and
      flexible screening based on docking results when protein structures with low
      resolution (or theoretical models) are targeted. We applied CoLBA to ligand
      binding prediction in several GPCRs. The predicted ligand-binding models were
      evaluated in site-directed mutagenesis experiments in collaborative research, and
      the enrichment rate of activated ligands was compared with random compounds in
      virtual screening simulations. We propose that CoLBA can be applied in large
      scale modeling of ligand-receptor complexes and virtual screening for GPCRs.

PMID- 17202794
TI  - [Characterization of novel genes regulating adipocyte differentiation].
AB  - The mid- and late stages of adipocyte differentiation are known to be regulated
      by transcription factors such as peroxisome proliferator-activated receptor
      (PPAR)gamma and CCAAT-box/enhancer binder protein (C/EBP) families. However,
      events in the early stage of adipocyte differentiation remain largely unknown. To
      gain insights into the molecular mechanisms underlying the beginning of adipocyte
      differentiation, we have isolated 102 genes, which are induced at the beginning
      of the differentiation of mouse 3T3-L1 preadipocytes, using the polymerase chain
      reaction (PCR)-subtraction method. Of these, 46 appear to be unknown genes. Since
      rapid amplification of cDNA end (RACE), cDNA library screening, and a genome
      database search have revealed that two of these genes are novel, we have named
      them factor for adipocyte differentiation (fad) 24 and fad158. The database
      research of amino acid sequences revealed that fad24 has a basic leucine zipper
      motif and an NOC domain, and fad158 has four transmembrane domains and eight
      leucine-rich repeats. The expression of fad24 and fad158 transiently increased
      after the addition of adipogenic inducers [insulin, dexamethasone, 3-isobutyl-1
      methylxanthine, fetal bovine serum (FBS)]. RNAi-mediated knockdown of fad24 or
      antisense fad158 inhibited adipogenesis of 3T3-L1 preadipocytes and decreased
      expressions of PPARgamma and C/EBPalpha. Furthermore, the constitutive
      overexpression of fad24 or fad158 in the mouse fibroblast cell line NIH-3T3
      resulted in adipocyte conversion when stimulated with adipogenic inducers and
      PPARgamma ligand BRL49653. Moreover, it was found that FAD24 localizes in the
      nucleus, especially within nuclear speckles and nucleolus, and FAD158 localizes
      to the endoplasmic reticulum (ER). Taken together, fad24 and fad158 appear to
      regulate adipocyte differentiation by activating the PPARgamma pathway.

PMID- 17202795
TI  - [Transcription factor EPAS1 regulates insulin signaling pathway].
AB  - Obesity, which results from adipose differentiation and adipocyte hypertrophy, is
      a primary risk factor of these life-style-diseases. Obesity, is primary risk
      factor of these life-style-diseases, results from adipose differentiation and
      adipocyte hypertrophy. Adipose differentiation is regulated by several
      transcriptional factors, and we have focused here on the roles played by
      endothelial PAS domain protein1 (EPAS1) in adipogenesis. EPAS1 was identified as
      a factor responsible for hypoxia responses, such as angiogenesis, here we
      demonstrated that EPAS1 is highly induced during adipose differentiation in vivo
      and in vitro. We then analyzed EPAS1 promoter activity during adipose
      differentiation in 3T3-L1 cells. We showed that the sequence -478/-445 is
      responsible for the up-regulation of EPAS1 expression during adipose
      differentiation and that the activity of this region is controlled by Sp1 and
      Sp3. To examine whether EPAS1 exerts an influence on adipogenesis, we
      overexpressed dominant negative form of EPAS1 in 3T3-L1 cells. The expression of
      EPAS1 (1-485) allowed cells to accumulate only a minimum amount of lipid
      droplets. Therefore, induction of EPAS1 expression is necessary for execution of
      adipose differentiation program. The mechanism involves the direct
      transcriptional regulation of Glut1, Glut4 and IRS3 genes by EPAS1. These results
      also confirmed that the protein level of EPAS1 was increased by insulin
      stimulation in adipocytes. Taken together, this result also indicated that EPAS1
      plays a role in the part of insulin action. Therefore, these results suggest that
      the quantitative and functional alteration of EPAS1 are involved in metabolic
      syndrome occurrence.

PMID- 17202796
TI  - [Transcriptional regulation of metabolic switching PDK4 gene under various
      physiological conditions].
AB  - Pyruvate dehydrogenase kinase 4 (PDK4) phosphorylates and inactivates the
      pyruvate dehydrogenase complex to respond to physiologic conditions. This
      response switches the energy source from glucose to fatty acids to maintain blood
      glucose levels. Transcription of the PDK4 gene is activated by fasting or by the
      administration of a peroxisome proliferator-activated receptor alpha (PPARalpha)
      ligand in a tissue-specific manner. However, the two mechanisms to induce PDK4
      mRNA as well as the relationship between the two have not been studied in detail.
      In this study, we show that the two mechanisms are independent, at least in the
      mouse skeletal muscle, and that estrogen-related receptor alpha (ERRalpha) is
      directly involved in the PPARalpha-independent transcriptional activation of the
      PDK4 gene with peroxisome proliferator-activated receptor gamma co-activator
      1alpha (PGC-1alpha) as a specific partner. The latter conclusion is based on the
      following evidence: 1) Deletion and point mutation analyses of the cloned mouse
      PDK4 gene promoter sequence identified an exact possible ERRalpha-binding motif
      as the PGC-1alpha responsive element. 2) The overexpression of ERRalpha by
      cotransfection enhanced, and the knocking down of it by specific shRNAs
      diminished, the PGC-1alpha-dependent activation. 3) Specific binding of ERRalpha
      to the identified PGC-1alpha-responsive sequence of the mouse PDK4 promoter was
      confirmed in the electrophoresis mobility shift assay using anti-ERRalpha
      antibodies. These results suggest that PGC-1alpha plays an essential role not
      only in regulating the amounts of energy creating enzymes, but also at the step
      of metabolic switching with unevenly distributed tissue transcription factors
      such as ERRalpha in the skeletal muscle, thus harmonizing tissue-specific
      functions and energy metabolism.

PMID- 17202797
TI  - [Adrenoleukodystrophy: structure and function of ALDP, and intracellular behavior
      of mutant ALDP with naturally occurring missense mutations].
AB  - Adrenoleukodystrophy (ALD) is an inherited disorder characterized by progressive
      demyelination of the central nervous system and adrenal dysfunction. The
      biochemical characterization is based on the accumulation of pathgnomonic amounts
      of saturated very long-chain fatty acid (VLCFA; C>22) in all tissues, including
      the brain white matter, adrenal glands, and skin fibroblasts, of the patients.
      The accumulation of VLCFA in ALD is linked to a mutation in the ALD (ABCD1) gene,
      an ABC subfamily D member. The ALD gene product, so-called ALDP (ABCD1), is
      thought to be involved in the transport of VLCFA or VLCFA-CoA into the
      peroxisomes. ALDP is a half-sized peroxisomal ABC protein and it has 745 amino
      acids in humans. ALDP is thought to be synthesized on free polysomes,
      posttranslationally transported to peroxisomes, and inserted into the membranes.
      During this process, ALDP interacts with Pex19p, a chaperone-like protein for
      intracellular trafficking of peroxisomal membrane protein (PMP), the complex
      targets Pex3p on the peroxisomal membranes, and ALDP is inserted into the
      membranes. After integration into the membranes, ALDP is thought to form mainly
      homodimers. Here, we chose nine arbitrary mutations of human ALDP with naturally
      occurring missense mutations and examined the intracellular behavior of their
      ALDPs. We found that mutant ALDP (S606L, R617H, and H667D) was degraded together
      with wild-type ALDP by proteasomes. These results suggest that the complex of
      mutant and wild-type ALDP is recognized as misfolded proteins and degraded by the
      protein quality control system associated with proteasomes. Further, we found
      fragmentation of mutant ALDP (R104C) on peroxisomes and it was not inhibited by
      proteasomes inhibitors, suggesting that an additional protease(s) is also
      involved in the quality control of mutant ALDP. In addition, mutation of ALDP
      (Y174C) suggests that a loop between transmembrane domains 2 and 3 is important
      for the targeting of ALDP to peroxisomes.

PMID- 17202798
TI  - Effects of propofol and midazolam on lipids, glucose, and plasma osmolality
      during and in the early postoperative period following coronary artery bypass
      graft surgery: a randomized trial.
AB  - It is not clear how levels of serum lipids and glucose and plasma osmolality
      change during propofol infusion in the pre- and postoperative period of coronary
      artery bypass graft surgery (CABG). This prospective, randomized, controlled
      trial evaluated changes in these parameters during propofol or midazolam infusion
      during and in the early postoperative period following surgery. Twenty patients
      undergoing CABG were randomized preoperatively into two groups: 10 patients
      received propofol (induction 1.5 mg/kg, maintenance 1.5 mg kg(-1) h(-1)) and 10
      patients received midazolam (induction 0.5 mg/kg, maintenance 0.1 mg kg(-1) h(
      1)). Both groups also received fentanyl (induction 20 mug/kg, maintenance 10
      microg kg(-1)). Serum lipids, glucose, and plasma osmolality were measured
      preinduction, precardiopulmonary bypass, at the end of cardiopulmonary bypass, at
      the end of surgery, and 4 and 24 h postoperatively. In the propofol group, we
      observed a significant increase in triglycerides and very low-density lipoprotein
      levels 4 h postoperatively. In the midazolam group, we observed a significant
      decrease in low-density lipoprotein, cholesterol at the end of cardiopulmonary
      bypass, end of surgery, and 4 and 24 h postoperatively and significant increase
      in osmolality at the end of cardiovascular bypass. Changes in glucose levels did
      not differ significantly different between the two groups. In patients with
      normal serum lipids, glucose, and plasma osmolality undergoing CABG, propofol
      infusion for maintenance anesthesia is not associated with dangerous changes in
      serum lipids, glucose, and plasma osmolality compared with midazolam. A propofol
      infusion technique for maintenance of anesthesia for cardiac surgery where serum
      lipids and glucose may be of concern could be recommended as an alternative to
      midazolam.

PMID- 17202799
TI  - Preparation and evaluation of a Carbopol/HPMC-based in situ gelling ophthalmic
      system for puerarin.
AB  - The purpose of this study was to develop a pH-triggered in situ gelling vehicle
      for ophthalmic delivery of puerarin. The effect of hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) on the aqueous solubility and in vitro corneal
      permeation of puerarin was also investigated. The puerarin solubility increased
      linearly and proportionally to the HP-beta-CD concentrations and 5% (w/v) HP-beta
      CD enhanced its ocular permeability significantly. Carbopol 980NF was used as the
      gelling agent in combination with HPMC (Methocel E4M) which acted as a viscosity
      enhancing agent. The optimum concentrations of Carbopol 980NF and HPMC E4M for
      the in situ gel-forming delivery systems were 0.1% (w/v) and 0.4% (w/v),
      respectively. When these two vehicles were combined, an in situ gel that had the
      appropriate gel strength and gelling capacity under physiological condition could
      be obtained. This combined solution could flow freely under non- physiological
      condition and showed the character of pseudoplastic fluid under both conditions.
      Both in vitro release studies and in vivo pharmacokinetics studies indicated that
      the combined polymer systems performed better in retaining puerarin than puerarin
      eye drops did. These results demonstrate that the Carbopol 980NF/HPMC E4M can be
      a viable alternative to conventional puerarin eye drops to enhance ocular
      bioavailability and patient compliance.

PMID- 17202800
TI  - Kinetic study on the degradation of meclophenoxate hydrochloride in alkaline
      aqueous solutions by high performance liquid chromatography.
AB  - A high performance liquid chromatographic method was developed and validated for
      determination of meclophenoxate hydrochloride (I) in the presence of its
      degradation product (p-chlorophenoxy acetic acid) (II). Separation of (I) from
      (II) was performed using a ZORBAX ODS column with a mobile phase consisting of
      0.2% triethylamine in 0.01 M ammonium carbonate: acetonitrile (70:30 v/v). The
      method showed high sensitivity with good linearity over the concentration range
      of 50 to 400 mug/ml. The method was successfully applied to the analysis of a
      pharmaceutical formulation containing (I) with excellent recovery. A kinetics
      investigation of the alkaline hydrolysis of (I) was carried out in sodium
      hydroxide solutions of 1, 1.5 and 2 N by monitoring the parent compound itself.
      The reaction order of (I) followed pseudo-first order kinetics. The activation
      energy could be estimated from the Arrhenius plot and it was found to be 12.331
      kcal/mole.

PMID- 17202801
TI  - Stability-indicating electrochemical methods for the determination of
      meclophenoxate hydrochloride and pyritinol dihydrochloride using ion-selective
      membrane electrodes.
AB  - The construction and electrochemical response characteristics of polyvinyl
      chloride (PVC) membrane sensors for the determination of meclophenoxate
      hydrochloride (I) and pyritinol dihydrochloride (II) in presence of their
      degradation products are described. The sensors are based on the use of the ion
      association complexes of (I) and (II) cation with sodium tetraphenyl borate and
      ammonium reineckate counteranions as ion-exchange sites in the PVC matrix. In
      addition beta-cyclodextrin (beta-CD) membranes were used in the determination of
      I and II. These ion pairs and beta-CD were then incorporated as electroactive
      species with ortho nitrophenyl octyl ether (oNPOE) as a plasticizer. Three PVC
      sensors were fabricated for each drug, i.e. meclophenoxate tetraphenyl borate
      (meclo-TPB), meclophenoxate reineckate (meclo-RNC) and meclophenoxate beta
      cyclodextrin (meclo-beta-CD), and the same was done for pyritinol (pyrit-TPB),
      (pyrit-RNC) and (pyrit-beta-CD). They showed near Nernestian responses for
      meclophenoxate over the concentration range 10(-5)-10(-2) with slopes of 52.73,
      51.64 and 54.05 per concentration decade with average recoveries of 99.92+/
      1.077, 99.96+/-0.502 and 100.03+/-0.763 for meclo-TPB, meclo-RNC and meclo-beta
      CD respectively. Pyritinol also showed near Nernestian responses over the
      concentration range of 3.162 x 10(-6) - 3.162 x 10(-4) for pyrit-TPB and pyrit
      RNC, and 10(-6) - 3.162 x 10(-4) for pyrit-beta-CD with slopes of 30.60, 31.10
      and 32.89 per concentration decade and average recoveries of 99.99+/-0.827,
      100.00+/-0.775 and 99.99+/-0.680 for pyrit-TPB, pyrit-RNC and pyrit-beta-CD
      respectively. The sensors were used successfully for the determination of I and
      II in laboratory prepared mixtures with their degradation products, in
      pharmaceutical dosage forms and in plasma.

PMID- 17202802
TI  - Effect of cyclosporine and tacrolimus on cytochrome p450 activities in human
      liver microsomes.
AB  - The effects of cyclosporine and tacrolimus on cytochrome P450 (CYP) 1A2-mediated
      7-ethoxyresorufin O-deethylation, CYP2C9-mediated tolbutamide hydroxylation,
      CYP2C19-mediated S-mephenytoin 4'-hydroxylation, CYP2D6-mediated debrisoquine 4
      hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, CYP3A4-mediated
      nifedipine oxidation, and CYP3A4-mediated testosterone 6beta-hydroxylation
      activities in human liver microsomes were compared. Cyclosporine and tacrolimus,
      at concentrations of 0.2 or 2 muM, neither inhibited nor stimulated any of the
      metabolic activities except for those of CYP3A4. On the other hand, cyclosporine
      and tacrolimus competitively inhibited CYP3A4-mediated nifedipine oxidation
      activity, with inhibition constants (K(i)) of 1.42 and 0.36 muM, respectively. In
      addition, 20 muM cyclosporine inhibited CYP2C19 and CYP2D6 activities by 29% and
      30%, respectively. These results suggest that tacrolimus would not cause
      clinically significant interactions with other drugs, which are metabolized by
      CYPs, via the inhibition of hepatic metabolism and that the reason why
      cyclosporine, but not tacrolimus, has a pharmacokinetic inhibitory effect might
      be that the dosage and/or the unbound concentrations around its metabolic enzymes
      are higher than those of tacrolimus, rather than the differences in the
      inhibition potential. Obvious substrate-dependent effects on CYP3A4-inhibition
      potential were not observed.

PMID- 17202803
TI  - [Leo Sternbach, an inventor of benzodiazepines].
AB  - A biography of Leo Sternbach, an inventor of benzodiazepine tranquillizers, is
      presented. It consists of (1) a societal desire for lifestyle pills, (2) Leo's
      birth in 1908 and youth, (3) education, (4) in Vienna, (5) in Zurich, (6) at
      Hoffmann-La Roche, Basel, (7) to the New World, (8) at Roche, Nutley NJ, (9)
      invention of the new drugs, (10) revolution of people's lifestyle, and (11)
      reward, retirement and obituary in 2005. This paper may be the first
      comprehensive biography of this remarkable chemist written in Japanese.

PMID- 17202805
TI  - Metastatic endobronchial melanoma.

PMID- 17202804
TI  - Gonadotropin-releasing hormone functionally antagonizes testosterone activation
      of the human androgen receptor in prostate cells through focal adhesion complexes
      involving Hic-5.
AB  - Gonadotropin-releasing hormone (GnRH) analogs constitute the most widely employed
      medical treatment for prostatic cancer. The predominant mechanism of action is
      presumed to be via the inhibition of gonadotropins and resultant decrease in
      androgen. However, GnRH analogs have also been shown to directly inhibit prostate
      cancer cells both in vitro and in vivo through antiproliferative cell cycle
      arrest and stimulation of apoptosis. Since the GnRH receptor has been shown to
      affect sex steroid hormone receptor function, we considered that part of GnRH
      analog actions on prostate cells may be mediated through modulation of the human
      androgen receptor. Using a model HEK293 cell line expressing the GnRH receptor,
      we demonstrated a novel signalling pathway of the GnRH receptor that induces
      nuclear translocation of the androgen receptor that renders it transcriptionally
      inactive. This mechanism involves the calcium-dependent tyrosine kinase Pyk2, the
      non-receptor tyrosine kinase c-Src and the focal adhesion protein/steroid
      receptor co-factor, Hic-5. In this setting there is a GnRH-induced association
      and nuclear translocation of the androgen receptor with Hic-5. GnRH-induced Pyk2
      activation opposed the association of Hic-5 with androgen receptor as
      overexpression of a dominant negative Pyk2 enhanced the GnRH-induced nuclear
      translocation of a green fluorescent protein-tagged human androgen receptor. GnRH
      induced c-Src activation resulted in the phosphorylation of expressed Hic-5 and
      promoted its association with the human androgen receptor. In contrast to
      testosterone, GnRH-induced nuclear translocation did not transcriptionally
      activate the androgen receptor. We then demonstrated that GnRH can also stimulate
      androgen receptor mobilization in human prostate PC3, BPH-1 and LNCaP cells, and
      in cultured rat ventral prostate cells through the same mechanism. To determine
      if GnRH could antagonize androgen effects in normal tissue, we examined the
      effect of GnRH on rat ventral prostate organ cultures and demonstrated that GnRH
      can functionally antagonize the actions of testosterone on prostate cell
      proliferation and tissue growth. This antagonism of testosterone action by GnRH
      may underlie in part the capacity of GnRH receptor activation to inhibit prostate
      tumor growth.

PMID- 17202806
TI  - Transmission of lung sounds through light clothing.
AB  - BACKGROUND: Doctors are exhorted to always place the stethoscope directly on the
      skin and never to auscultate through clothing. Nevertheless, casual observation
      reveals that doctors and even pulmonologists often violate this principle.
      OBJECTIVES: This study was designed to evaluate the sensitivity of two common
      stethoscopes when used through clothing. METHODS: Littmann Classic and Littmann
      Master Cardiology stethoscopes were studied under conditions of light (60-100 g),
      medium (240 g) and heavy (555 g) force when placed on a lung sound test platform
      with one or two layers of cloth (T-shirt material and flannel) interposed between
      the stethoscope and the test surface. The test platform was designed to mimic the
      acoustic and mechanical properties of the chest wall and was driven by amplified
      white noise. The recorded amplitude spectra were compared over a range of 150
      1,000 Hz. RESULTS: Compared to the sensitivity on a bare test platform surface,
      either fabric in single or double layers attenuated the sounds by a mean of 5-18
      dB under light pressure. This attenuation was nearly abolished by the addition of
      either medium or heavy force on the stethoscope head. CONCLUSIONS: The
      deleterious effect of one or two layers of indoor clothing on lung sounds
      acquired through a stethoscope can be negated by force on the stethoscope head
      making effective auscultation possible. Nevertheless, auscultation through
      clothing remains problematic due to the hindrance to inspection and percussion
      and the risk of acoustic artifacts caused by clothing.

PMID- 17202807
TI  - Elevated levels of beta-D-glucan in bronchoalveolar lavage fluid in patients with
      farmer's lung in Miyazaki, Japan.
AB  - BACKGROUND: Farmers may be often exposed to beta-D-glucan in moldy hay, since
      straw for feed can be stored throughout the year. OBJECTIVES: The aim of the
      present study was to clarify whether levels of beta-D-glucan, which modifies
      immune responses, are high in the respiratory tract in farmer's lung and whether
      beta-D-glucan participates in the pathogenesis of this condition. METHODS: We
      measured beta-D-glucan levels in the bronchoalveolar lavage fluid (BALF) of 10
      patients with farmer's lung, 4 with summer-type hypersensitivity pneumonitis (HP)
      and 10 healthy volunteers. Interleukin (IL)-8 and tumor necrosis factor (TNF)
      alpha levels in BALF were measured by enzyme-linked immunosorbent assay (ELISA).
      We investigated the effects of beta-D-glucan on nuclear factor (NF)-kappaB
      activation and on the release of IL-8 and TNF-alpha from small airway epithelial
      cells (SAECs) in vitro. RESULTS: beta-D-Glucan levels in the BALF of farmer's
      lung patients were increased compared to those in patients with summer-type HP
      and in healthy volunteers. Additionally, IL-8 levels in BALF were higher in
      farmer's lung than in summer-type HP, and TNF-alpha levels were equal in the two
      patient groups but raised compared to those in healthy volunteers. High, but not
      low, concentrations of beta-D-glucan were found to induce NF-kappaB activation in
      SAECs. IL-8 levels in the supernatant obtained from SAEC cultures were increased
      following the addition of beta-D-glucan in vitro. CONCLUSION: BALF from farmer's
      lung patients showed high beta-D-glucan levels, which may enhance the expression
      and release of cytokines through NF-kappaB activation in respiratory epithelial
      cells.

PMID- 17202808
TI  - Severe obstructive sleep apnea alleviated by oral appliance in a three-year-old
      boy.
AB  - This clinical report describes a 3.5-year-old boy suffering from chronic daytime
      fatigue, accumulated snoring and dramatically appearing apnea during sleep.
      Oxycardiorespirography revealed a breathing pattern similar to repetitive
      obstructive apnea and an oxygen saturation periodically dropping to 80%. During
      tidal breathing, fiberoptic bronchoscopy showed aspiration of the aryepiglottic
      folds and the epiglottis during inspiration. Adenotonsillar hypertrophy was
      excluded. Due to the acknowledged side effects from various surgical approaches
      and nasal continuous positive airway pressure, a removable, functional Fraenkel
      II oral appliance was applied during sleep. Clinical assessment demonstrated
      resolution of the main respiratory symptoms, and oxycardiorespirography revealed
      a fundamental reduction in periodic obstructive apnea and desaturation. In
      conclusion, we consider the use of an oral functional appliance for severe
      obstructive sleep apnea in children to be a valuable alternative to other
      treatment methods.

PMID- 17202809
TI  - Efficient adsorption of tumor necrosis factor with an in vitro set-up of the
      microspheres-based detoxification system.
AB  - BACKGROUND: The Microsperes-Based Detoxification System (MDS) represents a
      flexible therapeutic option for various diseases, depending on the specificity of
      the adsorbents applied. A potential application of the MDS is the supportive
      therapy of sepsis. METHODS: Microadsorbents for tumor necrosis factor (TNF) were
      prepared by immobilization of anti-TNF antibodies on cellulose (1-10 microm) and
      applied in an experimental set-up using a pool of human plasma (1 liter) spiked
      with TNF (800 pg/ml) and its soluble receptors (1,000 pg/ml each). Removal of TNF
      was compared using a plasma filter and the albumin-permeable filter Albuflow.
      RESULTS: Addition of 4 (2) g of adsorbent to the filtrate circuit reduced TNF
      concentrations in the pool by 80% (64%). Removal rates did not differ
      significantly for the different filters. TNF adsorption was not influenced by the
      presence of excess TNF receptors. CONCLUSIONS: Concentrations of mediators can be
      efficiently modulated with the MDS using small quantities of specific adsorbents.

PMID- 17202810
TI  - Erythromycin resistance in viridans streptococci bacteremia is clinically
      significant.

PMID- 17202811
TI  - Ramosetron versus ondansetron in the prevention of chemotherapy-induced
      gastrointestinal side effects: A prospective randomized controlled study.
AB  - BACKGROUND: This study observed and compared the preventive effects of ramosetron
      and ondansetron on gastrointestinal side effects caused by cisplatin-containing
      chemotherapy. METHODS: Fifty patients with malignant tumors undergoing their
      first chemotherapy were randomly divided into two groups, and each group received
      0.3 mg of ramosetron and 16 mg of ondansetron in a prospective crossover
      comparison study. RESULTS: Data were collected for analysis of the therapeutic
      effect in 47 cases and for adverse events in 50 cases. Both drugs showed similar
      results in regard to chemotherapy-induced gastrointestinal side effects, emesis
      and appetite loss on day 1, but by day 5, ramosetron was significantly better
      than ondansetron in terms of controlling appetite loss. From days 3-5, ramosetron
      tended to be more effective than ondansetron in its antiemetic action. The
      incidence of headache, fatigue and constipation was the same for both drugs.
      CONCLUSIONS: Ramosetron is a long-lasting and safe antiemetic agent.

PMID- 17202812
TI  - Vinblastine, a chemotherapeutic drug, inhibits palmitoylation of tubulin in human
      leukemic lymphocytes.
AB  - BACKGROUND: We have previously shown that tubulin, the major protein of
      microtubules, is posttranslationally modified by palmitoylation. In addition, we
      demonstrated that palmitoylation of tubulin is inhibited in vitro by
      stoichiometric levels of the chemotherapeutic drug, vinblastine. Here, we sought
      to determine whether a clinically relevant dose of vinblastine inhibits
      palmitoylation of tubulin in vivo. METHODS: Human CEM leukemic lymphocytes were
      incubated with [3H]palmitate in the presence and absence of a low, clinically
      relevant dose of vinblastine. [3H]palmitoylated tubulin was identified by two
      dimensional PAGE and autoradiography. RESULTS: We found, first, that tubulin was
      palmitoylated in CEM cells. Second, the clinically relevant dose of vinblastine
      inhibited palmitoylation of tubulin in vivo in CEM cells. In addition,
      microtubules were disassembled and cells became apoptotic. CONCLUSION: This study
      identifies a previously unknown mechanism of action of vinblastine, the
      depalmitoylation of tubulin, and suggests that depalmitoylation of tubulin may be
      a target for new chemotherapeutic drugs.

PMID- 17202813
TI  - Effect of rapamycin on hepatocyte function and proliferation induced by growth
      factors.
AB  - BACKGROUND: Rapamycin is a specific inhibitor of the mammalian target of
      rapamycin (mTOR). The effect of rapamycin on proliferation and cellular function
      was studied in hepatocytes stimulated by hepatocyte growth factor (HGF) or
      transforming growth factor-alpha (TGFalpha). METHODS AND RESULTS: When isolated
      rat hepatocytes were cultured at low density, the addition of HGF or TGFalpha
      increased DNA synthesis but did not affect albumin or fibrinogen concentrations
      in the medium. In contrast, in hepatocytes cultured at high density, the albumin
      and fibrinogen concentrations, but not DNA synthesis, were increased by HGF or
      TGFalpha. The HGF- or TGFalpha-induced increase in DNA synthesis and in albumin
      or fibrinogen concentrations was suppressed by the addition of rapamycin, as well
      as wortmannin, a phosphatidylinositol-3 kinase inhibitor. CONCLUSION: HGF and
      TGFalpha stimulate proliferation and function of hepatocytes depending upon the
      conditions, and rapamycin inhibited these stimulatory effects, possibly by
      inhibiting the mTOR-dependent signaling pathway.

PMID- 17202814
TI  - Applications of a blood-brain barrier technology platform to predict CNS
      penetration of various chemotherapeutic agents. 1. Anti-infective drugs.
AB  - Except for a few well-documented CNS therapeutics, quantitative data on blood
      brain barrier (BBB) permeation is incomplete, unreliable or nonexistent and this
      is a major impediment in BBB modeling. Furthermore, only the passive diffusion
      component is generally taken into account. Three techniques of modeling (in vivo,
      in vitro and in silico) were set up and compared. The in silico predicted
      permeation of 287 anti-infective drugs has been faced to clinical observations.
      Good correlations were observed between in vitro permeability coefficients,
      influx transfer coefficients from in vivo studies and Pe scores from the
      computational model. High Pe score values are associated with an increase of
      reported CNS side effects.

PMID- 17202815
TI  - Applications of a blood-brain barrier technology platform to predict CNS
      penetration of various chemotherapeutic agents. 2. Cationic peptide vectors for
      brain delivery.
AB  - BACKGROUND: SynB family peptides conjugated to several drugs have been shown to
      increase the brain uptake and in vivo activities of these drugs via an adsorptive
      mediated transcytosis mechanism. Based on both in vivo and in vitro experimental
      data, a cell uptake component has been added to our computational model of blood
      brain barrier. METHODS: In situ brain perfusion, in vitro cell model and a
      computational cell uptake model have been used to discover brain-penetrating
      properties of SynB peptides and to screen libraries of new rationally designed
      peptide vectors suitable for brain drug delivery. RESULTS AND CONCLUSION:
      Starting from small peptide vectors that enhance the brain transport coefficient,
      the BBB platform has made it possible to design libraries of peptide vectors with
      enhanced transport properties.

PMID- 17202816
TI  - Clarithromycin suppresses invasiveness of human lung adenocarcinoma cells.
AB  - BACKGROUND: It has been speculated that clarithromycin (CAM), a 14-membered ring
      macrolide, possesses antitumor effects besides antimicrobial and anti
      inflammatory effects. METHOD: We evaluated the effects of CAM on the growth and
      invasiveness of A549 lung adenocarcinoma cells. RESULTS: Although CAM did not
      affect the growth of A549 cells, the Matrigel invasion assay showed that the
      potential of invasion was diminished by CAM treatment. When analyzed by flow
      cytometry, CAM suppressed alpha(2)- and beta(1)-integrin expression. Furthermore,
      thymidine phosphorylase (TP) expression was diminished by CAM treatment in a dose
      dependent manner. A specific TP inhibitor also suppressed beta(1)-integrin
      expression in flow cytometric analysis. CONCLUSIONS: These results suggest that
      CAM may suppress invasive activity of A549 cells in part by diminishing the
      expression of TP, alpha(2)- and beta(1)-integrin, which may be a downstream
      signal of the TP pathway, and that CAM could be useful in the treatment of lung
      adenocarcinoma.

PMID- 17202818
TI  - The determinants of successful in-hospital rehabilitation in people aged 90 years
      and older.
AB  - BACKGROUND/OBJECTIVES: The very elderly constitute a subgroup of elderly who may
      respond differently than the younger elderly to medical intervention. This
      possibility has not previously been investigated. Our study investigates whether
      successful rehabilitation of the very elderly is possible within the current
      processes of care and also whether factors that help predict successful
      rehabilitation in all age elderly are applicable to the oldest old. METHODS: A
      retrospective case note analysis of all very elderly people (>or=90 years old)
      treated within in-patient elderly person rehabilitation facilities at the
      Northern General Hospital, Sheffield. Potential predictive factors analysed:
      Barthel index, main presenting illness, number of co-morbid conditions, number of
      regular prescribed medications, abbreviated mental test score, prior formal
      social services input, previous hospital admission within 1 year and serum
      albumin (g/l). Outcome measures reflecting success of rehabilitation: duration of
      rehabilitation (days), discharge destination to the same ('good outcome') or
      increased ('poor outcome') level of social and/or nursing care, readmission to
      hospital within 30 days of discharge and death during rehabilitation or within
      120 days of discharge. RESULTS: Of 230 nonagenarians admitted to inpatient
      elderly rehabilitation 47% required no increase in social support following their
      admission and 76% of those admitted from their own home were able to return
      there. Barthel index and the number of co-morbid conditions were the most
      influential predictors of success, with Barthel index predicting length of stay
      (p < 0.001), discharge destination (p < 0.001) and in-hospital mortality (p <
      0.01) and co-morbidity predicting readmission to hospital (p = 0.05), in-hospital
      mortality (p = 0.04) and survival (p = 0.05). On multi-variate analysis all other
      predictive factors analysed, except for presenting illness, were associated with
      at least one outcome measure (p < 0.05). CONCLUSION: Successful inpatient
      rehabilitation of the very elderly is possible. Factors that predict the success
      of rehabilitation of nonagenarians are similar to those associated with success
      in the younger elderly. The factors that most broadly predict success are Barthel
      index and the number of co-morbid conditions identified at admission to
      rehabilitation. Main presenting illness did not emerge as a predictor within this
      group.

PMID- 17202817
TI  - Molecular characterization of 8-methoxyfluoroquinolone resistance in a clinical
      isolate of methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND: Activity of gatifloxacin against clinical isolates of fluoroquinolone
      resistant Staphylococcus aureus is more potent than that of other
      fluoroquinolones such as norfloxacin and levofloxacin. To date, few reports have
      described high-level resistance to gatifloxacin in clinical isolates of S.
      aureus, although in vitro studies have shown that mutations in both DNA gyrase
      and topoisomerase IV were required for gatifloxacin resistance in S. aureus.
      METHODS: Minimum inhibitory concentrations were determined for fluoroquinolones
      and other antimicrobials in a methicillin-resistant S. aureus isolate that was
      cultured from blood of a patient with septicemia. Fluoroquinolone resistance was
      characterized by DNA sequencing and microbiologic assay. RESULTS: The isolate
      showed high-level resistance to fluoroquinolones including an 8
      methoxyfluoroquinolone, gatifloxacin (minimum inhibitory concentration 64
      microg/ml). Amino acid mutations of Ser80Tyr and Glu84Lys in GrlA and Ser84Leu
      and Ser85Pro in GyrA were possibly related to this resistance in methicillin
      resistant S. aureus HU2000-062, although efflux may play a minor role in
      resistance as well. CONCLUSION: GyrA and GrlA mutations mainly conferred to 8
      methoxyfluoroquinolone resistance in this isolate.

PMID- 17202819
TI  - Oral mucosal conditions and risk factors among elderly in a Turkish school of
      dentistry.
AB  - BACKGROUND: Prevalence studies are important to determine the oral health status
      and treatment needs of elderly people. Our aim was to obtain data for the
      prevalence of oral mucosal conditions (OMC) in a Turkish elderly sample and to
      compare our results with different geographic regions. OBJECTIVE: The purpose of
      this clinical-based study was to determine the prevalence of OMC and associated
      risk factors in a clinical-based Turkish elderly sample. METHODS: The study
      sample consisted of 700 patients >60 years old. The clinical examination of
      patients was performed by both authors. All participants were questioned about
      their general health status, medication use, oral hygiene habits, tobacco or
      alcohol use, use of dentures, and the length of denture use. Chi2 Pearson's test
      with Fisher's exact probability test was used to analyze the data. Logistic
      regression models were used to assess the influence of independent variables;
      odds ratios were calculated with 95% confidence intervals. Statistical
      significance was defined as p <0.05. RESULTS: OMC were recorded in 40.7% of the
      study sample. The logistic regression model revealed that male gender, length of
      denture use, smoking habit, and being a former smoker increased the probability
      of having an OMC. Smoking habit also increased the risk of having leukoplakia.
      The denture-related lesions accounted for 36.4% with the length of denture use
      and diabetes mellitus being significant risk factors for denture stomatitis and
      denture hyperplasia. The model for traumatic ulcer included medication use as a
      significant risk factor. CONCLUSIONS: Our results regarding an elderly Turkish
      sample support the studies of other populations where the prevalence of OMC was
      related to length of denture use, smoking, and gender. We also observed some
      important associations between denture-related lesions, systemic diseases, and
      medication use which require further investigation.

PMID- 17202820
TI  - Underlying factors in the association between depressed mood and mobility
      limitation in older people.
AB  - BACKGROUND: Depressed mood may either precede mobility limitation or follow from
      mobility limitation. OBJECTIVE: To compare mood status among people with manifest
      mobility limitation, those with preclinical mobility limitation and those without
      mobility limitation and investigate factors explaining the association between
      depressed mood and mobility limitation. DESIGN: Cross-sectional. SUBJECTS: 645
      community-living 75- to 81-year-old people. METHODS: Depressed mood was assessed
      using the Centre for Epidemiologic Studies Depression Scale (CES-D, cut-off score
      16); difficulty walking 500 m was assessed by self-report. Those reporting
      difficulty were categorised as having manifest mobility limitation. Those with no
      difficulty but reporting task modifications, such as reduced frequency of
      walking, were categorised as having preclinical mobility limitation. The
      association between depressed mood and mobility limitation was analysed using
      logistic regression analysis with gender, age, economic situation, the
      availability of a confidant, chronic conditions, and widespread pain as
      covariates. RESULTS: Depressed mood was found in 34% of subjects with manifest
      mobility limitation, in 26% of those with preclinical mobility limitation, and in
      13% of those without mobility limitation. The unadjusted odds ratio for depressed
      mood was 3.43 (95% CI 2.04-5.76) among subjects with manifest mobility limitation
      and 2.38 (95% CI 1.52-3.73) among those with preclinical mobility limitation,
      compared to those without mobility limitation. Adjustment for covariates reduced
      the risks to 2.10 (95% CI 1.15-3.82) and 1.99 (95% CI 1.24-3.20), respectively.
      Widespread pain explained 28% of the increased risk of depressed mood among those
      with manifest mobility limitation. CONCLUSION: The dose-response relationship
      between depressed mood and mobility limitation suggests that both conditions may
      progress simultaneously and may share aetiology, at least in part. Pain may be an
      underlying factor in both depressed mood and mobility limitation.

PMID- 17202822
TI  - Benign clear cell adenofibroma of the ovary. A case report with literature
      review.
AB  - Most clear cell neoplasms of the ovaries are carcinomas; benign and borderline
      clear cell tumors are uncommon. To date, only 12 cases of benign clear cell
      adenofibroma have been reported in the literature. Here we report a case of
      benign clear cell adenofibroma of the left ovary in a 51-year-old postmenopausal
      woman. Histological examination revealed widely spaced simple glands embedded in
      a dense fibrous stroma. The glands were lined by one to two layers of cells with
      abundant clear cytoplasm. The nuclei were bland and uniform in size and shape.
      There was minimal cytologic atypia in some areas. In this article we discussed
      the criteria for the diagnosis of benign and borderline clear cell adenofibromas
      and reviewed the literature.

PMID- 17202821
TI  - Two unsuccessful clinical trials on endometriosis and a few lessons learned.
AB  - In 1999, a phase II clinical trial on the use of fulvestrant to treat
      endometriosis was launched; yet after 7 years there is still no report on its
      outcome. In 2005, another trial on the use of raloxifene to treat endometriosis
      was terminated early due to unfavorable outcome. The two apparently unsuccessful
      clinical trials on endometriosis have taught us a few important lessons. First,
      we need to understand endometriosis through more basic research. We have also
      been reminded that human endometriosis trials differ from animal studies; anatomy
      and physiology are often divergent, and outcome measures are certainly different.
      Ectopic endometrium can differ significantly from eutopic tissue, and this issue
      needs to be more thoroughly explored. We believe human cell lines will prove to
      be an inexpensive and valuable tool for future preliminary evaluation of medical
      therapies as well as discerning pathophysiologic processes of the disease. Based
      on our current understanding of endometriosis, some concrete benchmarks can be
      established for testing or screening potential compounds in vitro. Finally,
      estrogen receptor modulators are often tissue-, cell-, and context-specific in
      their actions; they should not be simplistically grouped together nor should
      extrapolations from one compound to another be undertaken in a cavalier manner.

PMID- 17202823
TI  - A new method to determine mean adult height from incomplete follow-up data.
AB  - BACKGROUND/AIM: In long-term growth studies with adult height (AH) as outcome,
      reporting is often required while data are incomplete because some participants
      have not yet reached AH whereas others might be lost to follow-up. Current
      practice is to analyze only participants who did reach AH, which can easily give
      biased results. We introduce a new method into the area of growth research.
      METHODS: We used the data of patients from a registration database and a growth
      study. The new method uses growth data in time intervals. The percentage of
      children still growing and the mean growth at each interval are used to determine
      mean AH. RESULTS: With the new method, estimated mean AHs had smaller bias and
      standard error than with commonly used methods. The method is not hampered by a
      correlation between AH and age at reaching AH, unlike methods merely using
      patients who have reached AH. CONCLUSION: In contrast to commonly used methods,
      the new method provides valid results on mean AH when complete actual
      measurements of AH are not (yet) available, provided that drop-out, if any, is
      not related to (disappointing) growth. As it also uses observed data of children
      with incomplete follow-up, the method employs the data more effectively.

PMID- 17202824
TI  - Stage I seminoma.

PMID- 17202825
TI  - Aprepitant as salvage therapy in patients with chemotherapy-induced nausea and
      emesis refractory to prophylaxis with 5-HT(3) antagonists and dexamethasone.
AB  - BACKGROUND: Despite prophylaxis with 5-HT(3) antagonists and dexamethasone,
      nausea/emesis are common chemotherapy- induced toxicities. The aim of this trial
      was to evaluate the efficacy of adding the NK1 antagonist aprepitant in patients
      refractory to standard prophylaxis. PATIENTS AND METHODS: Patients with
      significant nausea/vomiting despite prophylaxis with 5-HT(3) antagonists and
      dexamethasone were eligible. Aprepitant was added to the same antiemetic regimen
      used during previous cycles. RESULTS: 34 patients received 92 cycles of
      chemotherapy with aprepitant which was applied orally at 125 mg on day 1 and 80
      mg on days 2 and 3. All patients were refractory to standard antiemetic
      prophylaxis during cisplatin-based (n = 12) or other chemotherapy (n = 22). With
      the addition of aprepitant, all patients reported subjective improvement. The
      number of patients with nausea for >4 days decreased from 24 (71%) to 4 (12%) (p
      < 0.001), and the number of those with emesis for >2 days decreased from 26 (77%)
      to 0 (0%) (p < 0.001). In 12 patients receiving aprepitant for >2 cycles (3-8)
      the efficacy was maintained. No toxicity possibly related to aprepitant was
      observed. CONCLUSION: Aprepitant demonstrated significant activity in patients
      with nausea/vomiting refractory to prophylaxis with 5-HT(3) antagonists and
      dexamethasone.

PMID- 17202826
TI  - Gefitinib in combination with 5-fluorouracil (5-FU)/folinic acid and irinotecan
      in patients with 5-FU/oxaliplatin- refractory colorectal cancer: a phase I/II
      study of the Arbeitsgemeinschaft fur Internistische Onkologie (AIO).
AB  - BACKGROUND: Gefitinib is an epidermal growth factor receptor tyrosine kinase
      inhibitor. It potentiates cytotoxic drug activity in human xenografts. This phase
      I/II dose-finding study evaluated gefitinib in combination with a 5-fluorouracil
      (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI-AIO) regimen in patients with
      metastatic colorectal cancer. PATIENTS AND METHODS: Patients received gefitinib
      250 mg per day, and escalating doses of FOLFIRI-AIO i.v. (dose level (DL) 1:
      1600/ 500/60 mg/m(2); DL2: 1600/500/80 mg/m(2); DL3: 2000/500/ 80 mg/m(2)) weekly
      x 6. Dose-limiting toxicity (DLT) was determined in patients who completed 1
      cycle of therapy. RESULTS: 13 patients were enrolled. 1 out of 6 patients on DL1
      exhibited DLT (acute psychosis), and a total of 7 patients received DL2. Of
      those, 3 patients had DLT during cycle 1 (nausea/vomiting n = 2; diarrhea n = 1,
      fatigue n = 2). Recruitment was stopped at this DL because of the unfavorable
      toxicity profile observed during the first and subsequent treatment cycles (out
      of 7 patients: nausea/vomiting grade 3 n = 2, diarrhea grade 3 n = 2; fatigue n =
      3). Only 1 patient showed a partial remission, and 2 patients experienced
      stabilization of disease. CONCLUSIONS: Dose escalation had to be stopped early
      because of gastrointestinal toxicity and fatigue. This treatment regimen did not
      seem advantageous with respect to efficacy in comparison with FOLFIRIAIO alone.

PMID- 17202827
TI  - Solitary brain metastasis from classic biphasic pulmonary blastoma: a case report
      and review of the literature.
AB  - BACKGROUND: Classic biphasic pulmonary blastoma (CBPB) is a rare and aggressive
      primary malignancy, brain metastases of this type of tumor are even rarer. CASE
      REPORT: A 51-year-old male patient with a solitary cerebral metastasis, diagnosed
      ten months after left pneumonectomy for a CBPB, was treated by surgery and
      accelerated hypofractionated radiotherapy. RESULTS: The patient died 15 months
      after partial removal of the brain metastasis. Literature review revealed only 4
      cases of solitary brain metastases from this type of malignancy. The present case
      is the second one reported with a combined treatment of surgery and radiotherapy
      resulting in the longest survival. CONCLUSION: The best treatment for CBPB is
      difficult to determine because of the small number of cases, however, the
      combination of surgery with radiotherapy seems to be effective. The effectiveness
      of chemotherapy has not been ascertained.

PMID- 17202828
TI  - Effectiveness of cetuximab/gefitinib in the therapy of a sacral chordoma.
AB  - BACKGROUND: Chordomas are rare tumors of the skull base and the spine. Treatment
      is difficult since conventional radiotherapy or chemotherapy have only limited
      effects. PATIENT AND METHODS: A patient with a sacral chordoma and pulmonary
      metastases received initial surgery and radiotherapy for a local recurrence.
      After 11 months another local recurrence as well as a progression of the
      pulmonary metastases was documented. As tumor biopsies revealed the expression of
      the EGF receptor an individual treatment approach with a combination of cetuximab
      and gefitinib was performed. RESULTS: Under the treatment with
      cetuximab/gefitinib the local recurrence and the pulmonary metastases showed a
      partial response over the follow-up period of 9 months. To date no treatment
      failure was observed. CONCLUSIONS: The inhibition of the EGF pathway seems to be
      an effective measure in the treatment of a chordoma. Further follow-up will have
      to prove the long-term efficiency.

PMID- 17202829
TI  - Fulvestrant: a further treatment option for patients with metastatic uterine
      cancer?
AB  - BACKGROUND: Metastatic uterine cancer is notoriously difficult to treat,
      presenting a poor prognosis and a median survival time of less than 1 year. We
      present the successful use of the antiestrogen fulvestrant in an endocrine
      therapy-naive patient with advanced uterine cancer. CASE REPORT: A 64-year-old
      female presented with advanced uterine cancer 7.0 x 6.0 x 5.5 cm in size, with
      infiltration of the bladder. Previous chemotherapy and radiotherapy had been
      unsuccessful in preventing disease progression, and the patient developed hepatic
      metastases. As the tumor expressed a high level of estrogen receptor, treatment
      with fulvestrant 250 mg/month was initiated. RESULTS: 25 months after commencing
      fulvestrant treatment, the tumor had decreased in size to 4.8 x 3.5 x 3.2 cm, and
      the hepatic metastases were no longer detectable. Throughout treatment, the
      patient maintained a Karnofsky performance index of 90%. CONCLUSION: We suggest
      that fulvestrant may be an active and well-tolerated treatment option for
      patients with estrogen receptor- positive advanced uterine cancer.

PMID- 17202830
TI  - Maintenance therapy for multiple myeloma with particular emphasis on thalidomide.
AB  - Treatment standards are changing as a result of new findings in the therapy of
      multiple myeloma. So far, prednisone, dexamethasone and interferon-a have mainly
      been used as maintenance therapy after achieving remission or stable disease. At
      present, thalidomide is being considered as a new therapeutic option in several
      studies investigating maintenance therapy. As a result of the dose dependence of
      adverse effects such as neuropathy, constipation, sedation/vertigo and
      bradycardia, individual adjustment of the thalidomide dose is recommended. Only
      isolated cases of thrombosis occurred in the maintenance phase of therapy, and
      discontinuation of therapy is generally not necessary. While important study
      results on the efficacy of thalidomide following conventional chemotherapy are
      still awaited, it is the best documented drug so far for maintenance therapy
      following autologous stem cell transplantation. An upgrade of the response was
      seen in 22-73% of patients, as well as a significant prolongation of progression
      free survival. For the first time, maintenance therapy with thalidomide showed a
      significant improvement in overall survival in a phase III study published
      recently. The tolerability of thalidomide could be further improved by including
      the option of intermittent administration of the drug.

PMID- 17202831
TI  - Treatment options, prognostic factors and selection of treatment in stage I
      seminoma.
AB  - Treatment options in patients with stage I seminoma include radiotherapy (RT),
      surveillance, and adjuvant chemotherapy. This patient population has virtually a
      100% cure rate whichever approach is taken. While adjuvant retroperitoneal RT has
      been the standard of care for the past 50-60 years, there is increasingly
      persuasive data that adjuvant RT in this setting is associated with a small but
      definite increased risk of second malignancy and cardiovascular death. The long
      term data from surveillance series have documented the safety of this approach,
      and it is now accepted that a policy of surveillance is the optimal management
      approach. This gives a relapse rate of 15%, and most patients can be successfully
      salvaged with RT. Second relapse after salvage RT occurs in a small proportion of
      cases, and these patients are cured with chemotherapy. Adjuvant chemotherapy
      using carboplatin has been investigated as an alternative strategy but has not
      lived up to its initial promise. If used, then 2 courses of treatment should
      probably be given. It must be remembered that 80-85% of patients with testicular
      seminoma require no treatment after orchiectomy, and the long-term side effects
      of any adjuvant treatment approach must be carefully considered.

PMID- 17202832
TI  - Hemorrhage results in hepatic insulin-sensitizing substance-dependent insulin
      resistance mediated by somatostatin in rats.
AB  - BACKGROUND/AIMS: Acute hemorrhage results in hyperglycemia regulated in a
      redundant manner by adrenal catecholamines and hepatic sympathetic nerves. In
      addition, insulin secretion is suppressed and insulin resistance is accounted for
      completely by elimination of the hepatic insulin-sensitizing substance (HISS)
      component of insulin action. Blockade of HISS action secondary to blood loss
      leads to a state known as HISS-dependent insulin resistance (HDIR) which results
      in a decrease in the glucose disposal action of insulin by 33 +/- 3%. METHODS:
      This paper describes nine studies that have explored the neuroendocrine control
      of HDIR that is produced in response to the stress of blood loss. The rapid
      insulin sensitivity test (RIST), a transient euglycemic clamp, was used to
      measure insulin sensitivity. To test the role of the adrenergic system, alpha-
      and beta-adrenergic receptor antagonists, phentolamine and propranolol, were
      tested for the ability to block HDIR produced by hemorrhage. RESULTS: Neither
      intervention was effective (32 +/- 6 and 36 +/- 3%, respectively). Exogenous
      somatostatin was shown to produce HDIR that could be blocked by the somatostatin
      receptor antagonist, cyclosomatostatin. Cyclosomatostatin completely blocked the
      development of HDIR that occurred following hemorrhage (RIST index 214 +/- 9
      control, 218 +/- 9 mg glucose/kg body weight after cyclosomatostatin plus
      hemorrhage). CONCLUSIONS: The adrenergic system is not involved in producing HDIR
      in response to hemorrhage. Somatostatin appears to be the hormonal regulator of
      this response and it is suggested that the somatostatin derives from a neural
      origin within the liver.

PMID- 17202833
TI  - Evidence for the presence of molecules related to the neuropeptide CGRP in two
      cephalopods, Sepia officinalis and Nautilus macromphalus: comparison with its
      target organ distribution.
AB  - Calcitonin gene-related peptide (CGRP) is a neuropeptide mainly involved in brain
      and cardiovascular functions in mammals. We investigated its presence and
      potential roles in two cephalopods, Sepia officinalis and Nautilus macromphalus.
      CGRP-like, but not calcitonin (CT)-like, molecules were detected by specific
      radioimmuno- and radioreceptor assays in the brain, optic lobes, branchial heart
      or afferent branchial vein and kidney. Gel exclusion chromatography of cephalopod
      brain extracts, followed by SDS-PAGE, indicated that CGRP-like molecules had a
      molecular weight of around 3 kDa, close to that of human CGRP. The distribution
      of CGRP target organs was characterized by binding studies in cuttlefish.
      Specific CGRP binding sites were detected in the brain, optic lobes, and kidney,
      indicating potential autocrine/paracrine roles of CGRP. Specific CGRP binding
      sites were also detected in the gills and shell sac that do not contain the
      peptide itself, indicating potential endocrine roles of CGRP. Accordingly, high
      circulating levels of CGRP-like molecules were detected in hemolymph of both
      cuttlefish and nautilus, unlike the situation in mammals. CGRP binding sites were
      further characterized in the cuttlefish gills by the Scatchard method. Our study
      indicates that the brain neurotransmitter role of CGRP could represent an ancient
      role in metazoa, already present in cephalopods and conserved among vertebrates.
      In contrast, the endocrine role of CGRP, which was suggested in cephalopods and
      also present in teleosts, may have been lost during the evolution of the tetrapod
      lineage. Our data support the hypothesis that CGRP represents the ancestral
      molecule of the CT/CGRP family appeared in metazoa before the vertebrate
      emergence.

PMID- 17202834
TI  - Efficient amplification of melanoma-specific CD8+ T cells using artificial
      antigen presenting complex.
AB  - In vitro large amplification of tumor-specific cytotoxic T lymphocytes (CTLs) and
      adoptive transfer of these cells is one of the most promising approaches to treat
      malignant diseases in which an effective immune response is not achieved by
      active immunization. However, generating sufficient numbers of tumor-specific
      CTLs stimulated with autologous antigen presenting cells (APCs) in vitro is one
      of the most problematic steps in the adoptive cell transfer (ACT) therapy. To
      circumvent this problem, we have developed an artificial antigen presenting
      complex (aAPCs) using MHC class I molecules loaded with a melanoma-specific TRP-2
      peptide epitope. Our results show that TRP-2-specific CD8+ T cells elicited by
      immunization with recombinant adenovirus expressing the mini-gene epitope are
      efficiently stimulated and amplified in vitro to a greater extent by aAPCs than
      by natural splenic APCs. These aAPC-induced CTLs recognized endogenously
      processed antigens present on B16F10 melanoma cells. Efficient stimulation and
      proliferation of antigen- specific T cells was also confirmed using ovalbumin
      peptide-loaded aAPCs and OT-I TCR transgenic cells. These results demonstrate
      that prior in vivo immunization, which increases the precursor frequency,
      simplifies posterior expansion of tumor- specific CD8+ T cells, and aAPCs is
      superior to autologous APC for in vitro amplification. This "prime and expand"
      regimen can be an alternative method for large amplification of rare tumor
      specific CTLs and aAPCs should be a useful tool for ACT immunotherapy.

PMID- 17202835
TI  - Berberine reduces the expression of adipogenic enzymes and inflammatory molecules
      of 3T3-L1 adipocyte.
AB  - Berberine (BBR), an isoquinoline alkaloid, has a wide range of pharmacological
      effects, yet its exact mechanism is unknown. In order to understand the anti
      adipogenic effect of BBR, we studied the change of expression of several
      adipogenic enzymes of 3T3-L1 cells by BBR treatment. First, we measured the
      change of leptin and glycerol in the medium of 3T3-L1 cells treated with 1
      micrometer, 5 micrometer and 10 micrometer concentrations of BBR. We also
      measured the changes of adipogenic and lipolytic factors of 3T3-L1. In 3T3-L1
      cells, both leptin and adipogenic factors (SREBP-1c, C/EBP-alpha, PPAR-gamma,
      fatty acid synthase, acetyl-CoA carboxylase, acyl-CoA synthase and lipoprotein
      lipase) were reduced by BBR treatment. Glycerol secretion was increased, whereas
      expression of lipolytic enzymes (hormone-sensitive lipase and perilipin) mRNA was
      slightly decreased. Next, we measured the change of inflammation markers of 3T3
      L1 cells by BBR treatment. This resulted in the down-regulation of mRNA level of
      inflammation markers such as TNF-alpha, IL-6, C- reactive protein and
      haptoglobin. Taken together, our data shows that BBR has both anti-adipogenic and
      anti-inflammatory effects on 3T3-L1 adipocytes, and the anti-adipogenic effect
      seems to be due to the down-regulation of adipogenic enzymes and transcription
      factors.

PMID- 17202836
TI  - 4-1BB (CD137) signals depend upon CD28 signals in alloimmune responses.
AB  - Our previous study has demonstrated that there is a significant delay of Balb/c
      cardiac allograft rejection in the C57BL/6 4-1BB-deficient knockout recipient. In
      this study, we examined the effect of combined blockade of the 4-1BB and CD28
      costimulatory pathways on cardiac allograft rejection in the C57BL/6-->Balb/c
      model. A long-term cardiac allograft survival was induced in CD28/4-1BB-
      deficient mice (>100 days survival in 3 of 4 mice), which was comparable with
      CD28-deficient mice (>100 days survival in 2 of 5 mice; P<0.2026). There was no
      long-term cardiac allograft survival in either wild-type (WT) or 4-1BB-deficient
      mice, even though 4-1BB-deficient recipients showed a significant delay of
      cardiac allograft rejection than WT mice. An in vitro mixed leukocyte reaction
      (MLR) assay showed that 4-1BB-deficient and WT mouse T cells had a similar
      responsiveness to allostimulation, whereas CD28- and CD28/4-1BB-deficient mouse T
      cells had a defective responsiveness to allostimulation. Furthermore, 4-1BB
      deficient mice showed a similar CTL but an elevated Ab response against
      alloantigens as compared to WT mice, and the alloimmune responses of 4-1BB
      deficient mice were abrogated in the CD28-deficient background. Overall, these
      results indicate that the CD28 costimulatory pathway plays a major role in the
      alloimmune response and that 4-1BB signals are dependent upon CD28 signals.

PMID- 17202837
TI  - Trichostatin A induces apoptosis in lung cancer cells via simultaneous activation
      of the death receptor-mediated and mitochondrial pathway?
AB  - Trichostatin A (TSA), originally developed as an antifungal agent, is one of
      potent histone deacetylase (HDAC) inhibitors, which are known to cause growth
      arrest and apoptosis induction of transformed cells, including urinary bladder,
      breast, prostate, ovary, and colon cancers. However, the effect of HDAC
      inhibitors on human non-small cell lung cancer cells is not clearly known yet.
      Herein, we demonstrated that treatment of TSA resulted in a significant decrease
      of the viability of H157 cells in a dose-dependent manner, which was revealed as
      apoptosis accompanying with nuclear fragmentation and an increase in sub-G0/G1
      fraction. In addition, it induced the expression of Fas/FasL, which further
      triggered the activation of caspase-8. Catalytic activation of caspase-9 and
      decreased expression of anti-apoptotic Bcl-2 and Bcl-XL proteins were observed in
      TSA-treated cells. Catalytic activation of caspase-3 by TSA was further confirmed
      by cleavage of pro-caspase-3 and intracellular substrates, including poly (ADP
      ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease
      (ICAD). In addition, a characteristic phenomenon of mitochondrial dysfunction,
      including mitochondrial membrane potential transition and release of
      mitochondrial cytochrome c into the cytosol was apparent in TSA-treated cells.
      Taken together, our data indicate that inhibition of HDAC by TSA induces the
      apoptosis of H157 cells through signaling cascade of Fas/FasL-mediated extrinsic
      and mitochondria-mediated intrinsic caspases pathway.

PMID- 17202838
TI  - p53 overexpression represses androgen-mediated induction of NKX3.1 in a prostate
      cancer cell line.
AB  - Prostate cancer is a disease involving complicated multiple-gene alterations.
      Both NKX3.1 and p53 are related to prostate cancer and play crucial roles in
      prostate cancer progression. However, little is known about the relationships and
      interactions between p53 and NKX3.1 in prostate cancer. We found that NKX3.1
      expression is down-regulated by over-expression of wild type (wt) p53 in prostate
      cancer LNCaP cells. NKX3.1 is down-regulated at both the mRNA and protein levels
      by p53 over- expression due to either transient transfection of exogenous p53 or
      induction of endogenous p53. p53 over-expression represses androgen-induced
      transactivation of NKX3.1 by inhibiting the promoter of the androgen acceptor
      (AR) gene and by blocking AR-DNA binding activity. In addition, transfection with
      the p21 expression vector (pPSA-p21) showed that p21 does not reduce NKX3.1
      expression, indicating that NKX3.1 expression is not the result of nonspecific
      effects of cell growth arrest. Our results provide biochemical and cellular
      biologic evidence that NKX3.1 is down-regulated by p53 over-expression in
      prostate cancer cells.

PMID- 17202839
TI  - zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad
      pathway in apoptosis of p815 mastocytoma cells.
AB  - In a preliminary study, we found that benzyloxycarbonyl-Val-Ala-Asp(OMe)
      fluoromethylketone (zVAD- fmk), unlike Boc-aspartyl(OMe)-fluoromethylketone (BocD
      fmk), at usual dosage could not prevent genistein-induced apoptosis of p815
      mastocytoma cells. This study was undertaken to reveal the mechanism underlying
      the incapability of zVAD-fmk in preventing this type of apoptosis. We observed
      that 14-3-3 protein level was reduced in genistein-treated cells and that BocD
      fmk but not zVAD-fmk prevented the reduction of 14-3-3 protein level and the
      release of Bad from 14-3-3. We also demonstrated that truncated Bad to Bcl-xL
      interaction in genistein- treated cells was prevented by BocD-fmk but not by zVAD
      fmk treatment. Our data indicate that BocD- fmk, compared to zVAD-fmk, has a
      certain preference for inhibiting 14-3-3/Bad signalling pathway. We also
      elucidated that this differential efficacy of BocD-fmk and zVAD-fmk resulted from
      the different effect in inhibiting caspase-6 and that co-treatment of zVAD-fmk
      and caspase-6 specific inhibitor substantially prevented genistein-induced
      apoptosis. Our data shows that caspase-6 plays a role on Bad/14-3-3 pathway in
      genistein-induced apoptosis of p815 cells, and that the usual dose of zVAD-fmk,
      in contrast to BocD-fmk, did not prevent caspase-6 acting on 14-3-3/Bad-mediated
      event.

PMID- 17202840
TI  - Epidemiological comparisons of codon usage patterns among HIV-1 isolates from
      Asia, Europe, Africa and the Americas.
AB  - To investigate the genomic properties of HIV-1, we collected 3,081 sequences from
      the HIV Sequence Database. The sequences were categorized according to sampling
      region, country, year, subtype, gene name, and sequence and were saved in a
      database constructed for this study. The relative synonymous codon usage (RSCU)
      values of matrix, capsid, and gp120 and gp41 genes were calculated using
      correspondence analysis. The synonymous codon usage patterns based on the
      geographical regions of African countries showed broad distributions; when all
      the other regions, including Asia, Europe, and the Americas, were taken into
      account, the Asian countries tended to be divided into two groups. The sequences
      were clustered into nine non-CRF subtypes. Among these, subtype C showed the most
      distinct codon usage pattern. To determine why the codon usage patterns in Asian
      countries were divided into two groups for four target genes, the sequences of
      the isolates from the Asian countries were analyzed. As a result, the synonymous
      codon usage patterns among Asian countries were divided into two groups, the
      southern Asian countries and the other Asian countries, with subtype 01_AE being
      the most dominant subtype in southern Asia. In summary, the synonymous codon
      usage patterns among the individual HIV-1 subtypes reflect genetic variations,
      and this bioinformatics technique may be useful in conjunction with phylogenetic
      methods for predicting the evolutionary patterns of pandemic viruses.

PMID- 17202841
TI  - Recombinant adeno-associated virus mediated gene transfer in a mouse model for
      homocystinuria.
AB  - Homocystinuria is a metabolic disorder caused by a deficiency of cystathionine
      beta-synthase (CBS). The major clinical symptoms of this disease are mental
      retardation, lens dislocation, vascular disease with life-threatening
      thromboembolisms, and skeletal deformities. The major treatments for CBS
      deficiency include pharmacologic doses of pyridoxine or dietary restriction of
      methionine. There is currently no effective long-term treatment to lower the
      elevated plasma levels of homocysteine. However, gene therapy could be an
      effective novel approach for the treatment of homocystinuria. A recombinant adeno
      associated virus vector carrying human CBS cDNA (rAAV-hCBS) was constructed and
      administered to CBS-/- mice by intramuscular (IM) and intraperitoneal (IP)
      injections. Serum homocysteine concentrations significantly decreased in treated
      mice compared with age-matched controls two weeks after treatment. The treated
      CBS-/- mice had life spans 3-7 days longer compared with untreated CBS-/- mice.
      In CBS-/- mice treated with rAAV-hCBS via IP injection, the vector was detected
      in all organs examined including liver, spleen, and kidney, and CBS gene
      expression was observed by immunohistochemical staining in the liver. These
      results indicate the efficacy of gene delivery and demonstrate the possibility of
      gene therapy mediated by AAV gene transfer in this mouse model of homocystinuria.

PMID- 17202842
TI  - Heterozygosities of 735 microsatellite markers and background linkage
      disequilibrium in the Korean population.
AB  - Suitability of a specific population for linkage disequilibrium mapping studies
      of complex traits may be assessed by investigating the background linkage
      disequilibrium (BLD). We are unaware of studies for quantifying the degree of BLD
      in the Korean population, although the population may be a good candidate for
      mapping of complex trait genes through whole-genome association studies. It is
      useful to investigate the properties of genetic isolates in East Asia and to
      compare them to genetic isolates in Europe. We analyzed the extent of BLD in the
      Korean population using 735 microsatellite markers and compared the results with
      the Icelander population, which is one of the European expanded genetic isolates.
      The Korean population exhibited a level of BLD comparable with the Icelander
      population. The inference of population structure using the model with admixture
      showed that each individual has allele copies originating from K populations in
      equal proportions. Therefore, we believe that factors other than genetic
      distance, such as recent admixture, have not contributed to the level of BLD. Our
      results showed that the Korean population, which is an expanded population with
      no evidence of admixture, has a BLD level comparable with the Icelander
      population. Therefore, the Korean population can be used for fine mapping of
      either complex traits or monogenic diseases.

PMID- 17202843
TI  - Dynamic changes of gangliosides expression during the differentiation of
      embryonic and mesenchymal stem cells into neural cells.
AB  - Stem cells are used for the investigation of developmental processes at both
      cellular and organism levels and offer tremendous potentials for clinical
      applications as an unlimited source for transplantation. Gangliosides, sialic
      acid-conjugated glycosphingolipids, play important regulatory roles in cell
      proliferation and differentiation. However, their expression patterns in stem
      cells and during neuronal differentiation are not known. Here, we investigated
      expression of gangliosides during the growth of mouse embryonic stem cells
      (mESCs), mesenchymal stem cells (MSCs) and differentiated neuronal cells by using
      high-performance thin-layer chromatography (HPTLC). Monosialoganglioside 1 (GM1)
      was expressed in mESCs and MSCs, while GM3 and GD3 were expressed in embryonic
      bodies. In the 9-day old differentiated neuronal cells from mESCs cells and MSCs,
      GM1 and GT1b were expressed. Results from immunostaining were consistent with
      those observed by HPTLC assay. These suggest that gangliosides are specifically
      expressed according to differentiation of mESCs and MSCs into neuronal cells and
      expressional difference of gangliosides may be a useful marker to identify
      differentiation of mESCs and MSCs into neuronal cells.

PMID- 17202844
TI  - The translation inhibitor anisomycin induces Elk-1-mediated transcriptional
      activation of egr-1 through multiple mitogen-activated protein kinase pathways.
AB  - The early growth response-1 gene (egr-1) encodes a zinc-finger transcription
      factor Egr-1 and is rapidly inducible by a variety of extracellular stimuli.
      Anisomycin (ANX), a protein synthesis inhibitor, stimulates mitogen-activated
      protein kinase (MAPK) pathways and thereby causes a rapid induction of immediate
      early response genes. We found that anisomycin treatment of U87MG glioma cells
      resulted in a marked, time-dependent increase in levels of Egr-1 protein. The
      results of Northern blot analysis and reporter gene assay of egr-1 gene promoter
      (Pegr-1) activity indicate that the ANX- induced increase in Egr-1 occurs at the
      transcriptional level. Deletion of the serum response element (SRE) in the 5'
      flanking region of egr-1 gene abolished ANX-induced Pegr-1 activity. ANX induced
      the phosphorylation of the ERK1/2, JNK, and p38 MAPKs in a time-dependent manner
      and also induced transactivation of Gal4-Elk-1, suggesting that Elk-1 is involved
      in SRE-mediated egr-1 transcription. Transient transfection of dominant-negative
      constructs of MAPK pathways blocked ANX-induced Pegr-1 activity. Furthermore,
      pretreatment with specific MAPK pathway inhibitors, including the MEK inhibitor
      U0126, the JNK inhibitor SP600125, and the p38 kinase inhibitor SB202190,
      completely inhibited ANX-inducible expression of Egr-1. Taken together, these
      results suggest that all three MAPK pathways play a crucial role in ANX-induced
      transcriptional activation of Pegr-1 through SRE-mediated transactivation of Elk
      1.

PMID- 17202845
TI  - Decreased expression of DNA repair proteins Ku70 and Mre11 is associated with
      aging and may contribute to the cellular senescence.
AB  - The gradual loss of telomeric DNA can contribute to replicative senescence and
      thus, having longer telomeric DNA is generally considered to provide a longer
      lifespan. Maintenance and stabilization of telomeric DNA is assisted by binding
      of multiple DNA-binding proteins, including those involved in double strand break
      (DSB) repair. We reasoned that declining DSB repair capacity and increased
      telomere shortening in aged individuals may be associated with decreased
      expression of DSB repair proteins capable of telomere binding. Our data presented
      here show that among the DSB repair proteins tested, only the expression of Ku70
      and Mre11 showed statistically significant age-dependent changes in human
      lymphocytes. Furthermore, we found that expressions of Ku70 and Mre11 are
      statistically correlated, which indicate that the function of Ku70 and Mre11 may
      be related. All the other DSB repair proteins tested, Sir2, TRF1 and Ku80, did
      not show any significant differences upon aging. In line with these data, people
      who live in the regional community (longevity group), which was found to have
      statistically longer average life span than the rest area, shows higher level of
      Ku70 expression than those living in the neighboring control community. Taken
      together, our data show, for the first time, that Ku70 and Mre11 may represent
      new biomarkers for aging and further suggest that maintenance of higher
      expression of Ku70 and Mre11 may be responsible for keeping longer life span
      observed in the longevity group.

PMID- 17202846
TI  - Association of common promoter polymorphisms of MCP1 with hepatitis B virus
      clearance.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant cancers
      closely associated with chronic infection by the hepatitis B virus (HBV) or the
      hepatitis C virus (HCV) throughout the world. In this study, the genetic
      associations of 20 known polymorphisms in eight candidate genes, including
      angiotensinogen (AGT), cadherin 1 (CDH1), cyclooxygenase 2 (COX2), monocyte
      chemotactic protein-1 (MCP1), multidrug resistance 1 (MDR1), chemokine ligand 5
      (RANTES), thrombospondin 2 (THBS2), and thrombospondin 4 (THBS4), were analyzed
      in a large chronic hepatitis B cohort (n=1,095) recruited from the Korean
      population. In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and
      vimentin (VIM) identified in this study were also genotyped. Using logistic
      regression analysis controlling possible confounding factors, one common
      (freq.=0.367) promoter polymorphism of MCP1 (MCP1-2518G>A) among analyzed
      polymorphisms was significantly associated with clearance of HBV infection. The
      frequency of homozygotes for the MCP1-2518A allele (MCP1-2518A/A) among chronic
      hepatitis B virus (HBV) carrier patients was significantly higher than that among
      spontaneously recovered (SR) subjects (17.7% vs. 10.4%)(OR=1.78, P=0.004). Our
      findings imply a plausible explanation for the contribution of host genetic
      determinants to the variable outcome of HBV infection, which might provide
      valuable information for future genetic study in this area.

PMID- 17202848
TI  - Discovery of a small-molecule inhibitor for kidney ADP-ribosyl cyclase:
      Implication for intracellular calcium signal mediated by cyclic ADP-ribose.
AB  - ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca2+-mobilizing second messenger,
      cyclic ADP- ribose (cADPR), from beta-NAD+. A prototype of mammalian ADPR
      cyclases is a lymphocyte antigen CD38. Accumulating evidence indicates that ADPR
      cyclases other than CD38 are expressed in various cells and organs. In this
      study, we discovered a small molecule inhibitor of kidney ADPR-cyclase. This
      compound inhibited kidney ADPR-cyclase activity but not CD38, spleen, heart or
      brain ADPR-cyclase activity in vitro. Characterization of the compound in a cell
      based system revealed that an extracellular calcium-sensing receptor (CaSR)-
      mediated cADPR production and a later long-lasting increase in intracellular Ca2+
      concentration ([Ca2+]i) in mouse mesangial cells were inhibited by the pre
      treatment with this compound. In contrast, the compound did not block CD3/TCR
      induced cADPR production and the increase of [Ca2+]i in Jurkat T cells, which
      express CD38 exclusively. The long-lasting Ca2+ signal generated by both
      receptors was inhibited by pre-treatment with an antagonistic cADPR derivative, 8
      Br-cADPR, indicating that the Ca2+ signal is mediated by the ADPR-cyclase
      metabolite, cADPR. Moreover, among structurally similar compounds tested, the
      compound inhibited most potently the cADPR production and Ca2+ signal induced by
      CaSR. These findings provide evidence for existence of a distinct ADPR-cyclase in
      the kidney and basis for the development of tissue specific inhibitors.

PMID- 17202847
TI  - Tyrosine phosphatase and cytochrome P450 activity are critical in regulating
      store-operated calcium channels in human fibroblasts.
AB  - Diverse signaling pathways have been proposed to regulate store-operated calcium
      entry (SOCE) in a wide variety of cell types. However, it still needs to be
      determined if all of these known pathways operate in a single cell type. In this
      study, we examined involvement of various signaling molecules in SOCE using human
      fibroblast cells (HSWP). Bradykinin (BK)-stimulated Ca2+ entry, previously shown
      to be via SOCE, is enhanced by the addition of vanadate, an inhibitor of tyrosine
      phosphatases. Furthermore, SOCE is regulated by cytochrome P-450, as demonstrated
      by the fact that the products of cytochrome P-450 activity (14,15 EET) stimulated
      SOCE while econazole, an inhibitor of cytochrome P450, suppressed BK-stimulated
      Ca2+ entry. In contrast, Ca2+ entry was unaffected by the guanylate cyclase
      inhibitor LY83583, or the membrane permeant cyclic GMP analog 8-bromo-cyclic GMP
      (8-Br-cGMP). Neither nitric oxide donors nor phorbol esters affected BK
      stimulated Ca2+ entry. SOCE in HSWP cells is primarily regulated by tyrosine
      phosphorylation and the cytochrome P-450 pathway, but not by cyclic GMP, nitric
      oxide, or protein kinase C. Thus, multiple pathways do operate in a single cell
      type leading to the activation of Ca2+ entry and some of these signaling pathways
      are more prominently involved in regulating calcium entry in different cell
      types.

PMID- 17202849
TI  - No association of prion protein gene polymorphisms with Alzheimer's disease in
      Korean population.
AB  - The polymorphism at codon 129 (M129V) of the human prion protein gene (PRNP) is a
      known risk factor for Creutzfeldt-Jakob disease (CJD) in Caucasians. There are
      few reports of this polymorphism's effect on memory and on the risk of
      Alzheimer's disease (AD). The M129V genotype distributions among Asians are very
      different from Caucasians. Another polymorphism, codon 219 (E219K) is not found
      in Caucasians. We investigated two polymorphisms of PRNP, M129V (rs1799990) and
      E219K (rs1800014) in 297 Korean AD patients and 217 healthy subjects. The
      analysis of the genotype and allele distributions showed no significant
      difference between the AD patients and the controls in both polymorphisms (P=0.19
      genotype, P=0.51 allele for M129V; P=0.64 genotype, P=0.50 allele for E219K).
      Also, the PRNP polymorphisms were not significantly associated with AD when the
      populations were stratified for the presence or absence of apolipoprotein E
      epsilon4 (ApoE-epsilon4) allele. These results suggest that the PRNP genetic
      variants are not associated with the risk for AD in Korean population.

PMID- 17202850
TI  - Neural cell adhesion molecule (NCAM) induces neuronal phenotype acquisition in
      dominant negative MEK1-expressing hippocampal neural progenitor cells.
AB  - It has been shown that neural cell adhesion molecule (NCAM)-induced neuronal
      differentiation is extracellular signal-regulated kinase (ERK)-dependent.
      However, an involvement of the mitogen activated protein kinase (MAPK) kinase
      (MEK), an upstream kinase of ERK, has not been directly demonstrated in this
      process. Therefore, we investigated whether the MEK1 plays a critical role in the
      NCAM-induced neuronal differentiation of hippocampal neural progenitor cells
      (NPCs). NPCs were transiently transfected with expression plasmids encoding
      activated or dominant negative (DN) forms of MEK1. The expression of DN MEK1
      inhibited neuronal phenotype acquisition and soluble NCAM rescued the defect in
      the neuronal phenotype acquisition in DN-MEK1-transfected cells, suggesting that
      NCAM might contribute to the neuronal differentiation via distinct, parallel
      pathways including the MEK pathway. In cells expressing wild type MEK1 or
      constitutively active MEK1 on the other hand, the percentage of cells positive
      for beta-tubulin type III (Tuj1), a marker for early postmitotic neurons, was
      higher than seen in vector-transfected cells. These results suggest that the
      activation of MEK1 is required for obtaining neuronal phenotype in NPCs.

PMID- 17202851
TI  - SUMOylation code in cancer development and metastasis.
AB  - Protein modification by small ubiquitin-like modifier (SUMO) controls diverse
      cellular functions of protein targets including transcription factors and
      coregulators mainly in the nucleus and participates in maintaining cellular
      homeostasis. In addition, SUMO system plays important roles in DNA damage repair
      and maintaining genome integrity. Thus, in some cases, the loss of control on
      SUMOylation or deSUMOylation processes causes a defect in maintaining homeostasis
      and hence gives a cue to cancer development. Furthermore, recent study showed
      that SUMO system is also involved in cancer metastasis. In this review, we will
      summarize and discuss the possible role of SUMO system in cancer development and
      metastasis.

PMID- 17202852
TI  - Normalization of microarray data: single-labeled and dual-labeled arrays.
AB  - DNA microarray is a powerful tool for high-throughput analysis of biological
      systems. Various computational tools have been created to facilitate the analysis
      of the large volume of data produced in DNA microarray experiments. Normalization
      is a critical step for obtaining data that are reliable and usable for subsequent
      analysis such as identification of differentially expressed genes and clustering.
      A variety of normalization methods have been proposed over the past few years,
      but no methods are still perfect. Various assumptions are often taken in the
      process of normalization. Therefore, the knowledge of underlying assumption and
      principle of normalization would be helpful for the correct analysis of
      microarray data. We present a review of normalization techniques from single
      labeled platforms such as the Affymetrix GeneChip array to dual-labeled platforms
      like spotted array focusing on their principles and assumptions.

PMID- 17202853
TI  - Spatio-temporal expression and regulation of dermatopontin in the early pregnant
      mouse uterus.
AB  - During endometrial differentiation the extracellular matrix (ECM) changes
      dramatically to prepare for implantation of the embryo. However, the genes
      regulating the ECM build-up in the uterine endometrium during early pregnancy are
      not well known. Using the PCR-select cDNA subtraction method, dermatopontin was
      identified in the uterus of a pregnant mouse on day 4 of gestation. Dermatopontin
      mRNA increased dramatically on day 3, and was at its highest level at the time of
      implantation. Administration of RU 486 significantly inhibited mRNA expression by
      day 4 of gestation, but ICI 182,780 did not. Progesterone markedly induced
      dermatopontin expression in ovariectomized uteri within 4 h of administration,
      whereas estrogen had little effect. In silico analysis revealed progesterone
      receptor binding sites in the dermatopontin promoter region. Decidualization did
      not induce expression of dermatopontin; instead dermatopontin mRNA became
      strongly localized at the interimplantation site. In situ hybridization revealed
      that expression gradually decreased in the luminal epithelial cells as pregnancy
      progressed, whereas it increased in the stromal cells. The pattern of
      localization and the changes of intensity of dermatopontin mRNA coincided with
      those of collagen. Collectively, these results strongly suggest that
      dermatopontin expression is steroid-dependent. They also suggest that, at the
      time of implantation, dermatopontin expression is primarily regulated spatio
      temporally by progesterone via progesterone receptors, and is modulated by the
      decidual response during implantation. Dermatopontin may be one of the regulators
      used to remodel the uterine ECM for pregnancy.

PMID- 17202854
TI  - Upregulation of isoprenoid pathway genes during enhanced saikosaponin
      biosynthesis in the hairy roots of Bupleurum falcatum.
AB  - In order to characterize saikosaponin biosynthesis in Bupleurum falcatum, the
      expression of five isoprenoid pathway genes and their relationship to
      saikosaponin accumulation in the hairy roots were analyzed. The hairy roots
      exhibited a rapid accumulation of saikosaponins when incubated in a root culture
      medium (3XRCM). Homology-based RT-PCR was used to isolate core fragments of five
      genes, HMGR, IPPI, FPS, SS, and OSC, from the hairy roots. The deduced amino acid
      sequences exhibited amino acid identities of more than 85% to previously reported
      genes. Using the fragments as probes, the expression of these five genes in the
      hairy roots during incubation in 3XRCM medium was examined. Expression of all
      five genes in the hairy roots increased soon after incubation. In particular, the
      SS and OSC genes were coordinately induced at 8 days of incubation, and their
      expression persisted throughout the incubation period. A quantitative HPLC
      analysis showed that the saikosaponin content of the hairy root culture also
      began to increase at 8 days of culture. The correlation between SS transcript
      level and saikosaponin content in the hairy roots suggests that transcriptional
      regulation plays a regulatory role in saikosaponin biosynthesis.

PMID- 17202855
TI  - Differential effects of two period genes on the physiology and proteomic profiles
      of mouse anterior tibialis muscles.
AB  - The molecular components that generate and maintain circadian rhythms of
      physiology and behavior in mammals are present both in the brain (suprachiasmatic
      nucleus; SCN) and in peripheral tissues. Examination of mice with targeted
      disruptions of either mPer1 or mPer2 has shown that these two genes have key
      roles in the SCN circadian clock. Here we show that loss of the clock gene mPer2
      affects forced locomotor performance in mice without altering muscle
      contractility. A proteomic analysis revealed that the anterior tibialis muscles
      of the mPer2 knockout mice had higher levels of glycolytic enzymes such as triose
      phosphate isomerase and enolase than those of either the wild type or mPer1
      knockout mice. In addition, the level of expression of HSP90 in the mPer2 mutant
      mice was also significantly higher than in wildtype mice. These results suggest
      that the reduced locomotor endurance of the mPer2 knockout mice reflects a
      greater dependence on anaerobic metabolism under stress conditions, and that the
      two canonical clock genes, mPer1 and mPer2, play distinct roles in the physiology
      of skeletal muscle.

PMID- 17202856
TI  - Circadian expression of clock genes in the rat eye and brain.
AB  - The light sensing system in the eye directly affects the circadian oscillator in
      the mammalian suprachiasmatic nucleus (SCN). To investigate this relationship in
      the rat, we examined the circadian expression of clock genes in the SCN and eye
      tissue during a 24 h day/night cycle. In the SCN, rPer1 and rPer2 mRNAs were
      expressed in a clear circadian rhythm like rCry1 and rCry2 mRNAs, whereas the
      level of BMAL1 and CLOCK mRNAs decreased during the day and increased during the
      night with a relatively low amplitude. It seems that the clock genes of the SCN
      may function in response to a master clock oscillation in the rat. In the eye,
      the rCry1 and rCry2 were expressed in a circadian rhythm with an increase during
      subjective day and a decrease during subjective night. However, the expression of
      Opn4 mRNA did not exhibit a clear circadian pattern, although its expression was
      higher in daytime than at night. This suggests that cryptochromes located in the
      eye, rather than melanopsin, are the major photoreceptive system for
      synchronizing the circadian rhythm of the SCN in the rat.

PMID- 17202857
TI  - Vitexin, an HIF-1alpha inhibitor, has anti-metastatic potential in PC12 cells.
AB  - Vitexin, a natural flavonoid compound identified as apigenin-8-C-b-D
      glucopyranoside, has been reported to exhibit antioxidative and anti-inflammatory
      properties. In this study, we investigated its effect on hypoxia-inducible factor
      1a (HIF-1a) in rat pheochromacytoma (PC12), human osteosarcoma (HOS) and human
      hepatoma (HepG2) cells. Vitexin inhibited HIF-1a in PC12 cells, but not in HOS or
      HepG2 cells. In addition, it diminished the mRNA levels of hypoxia-inducible
      genes such as vascular endothelial growth factor (VEGF), smad3, aldolase A,
      enolase 1, and collagen type III in the PC12 cells. We found that vitexin
      inhibited the migration of PC12 cells as well as their invasion rates, and it
      also inhibited tube formation by human umbilical vein endothelium cells (HUVECs).
      Interestingly, vitexin inhibited the hypoxia-induced activation of c-jun N
      terminal kinase (JNK), but not of extracellular-signal regulated protein kinase
      (ERK), implying that it acts in part via the JNK pathway. Overall, these results
      suggest the potential use of vitexin as a treatment for diseases such as cancer.

PMID- 17202858
TI  - A Survey of the Brassica rapa genome by BAC-end sequence analysis and comparison
      with Arabidopsis thaliana.
AB  - Brassica rapa ssp. pekinensis (Chinese cabbage) is an economically important crop
      and a model plant for studies on polyploidization and phenotypic evolution. To
      gain an insight into the structure of the B. rapa genome we analyzed 12,017 BAC
      end sequences for the presence of transposable elements (TEs), SSRs, centromeric
      satellite repeats and genes, and similarity to the closely related genome of
      Arabidopsis thaliana. TEs were estimated to occupy 14% of the genome, with 12.3%
      of the genome represented by retrotransposons. It was estimated that the B. rapa
      genome contains 43,000 genes, 1.6 times greater than the genome of A. thaliana. A
      number of centromeric satellite sequences, representing variations of a 176-bp
      consensus sequence, were identified. This sequence has undergone rapid evolution
      within the B. rapa genome and has diverged among the related species of
      Brassicaceae. A study of SSRs demonstrated a non-random distribution with a
      greater abundance within predicted intergenic regions. Our results provide an
      initial characterization of the genome of B. rapa and provide the basis for
      detailed analysis through whole-genome sequencing.

PMID- 17202859
TI  - The chemokine SDF-1alpha suppresses fibronectin-mediated in vitro lymphocytes
      adhesion.
AB  - Stromal cell-derived factor (SDF-1) is a CXC chemokine that selectively activates
      the CXCR4 chemokine receptor. Fibronectin is an intracellular matrix component
      that binds integrin and mediates cell-matrix adhesion. Activation of the integrin
      receptor can occur in two ways: by ligand binding (outside-in signaling), and in
      response to intracellular events (inside-out signaling). In the current study we
      showed that SDF-1a inhibited adhesion of T lymphocyte Jurkat cells resulting from
      binding high concentrations of fibronectin as well as that of THP-1 monocytes.
      The effect of SDF-1a on fibronectin-mediated adhesion was partly reversed by the
      CXCR4 receptor antagonist T140. Our results suggest that an SDF-1/ CXCR4 signal
      pathway modulates fibronectin-mediated lymphocytes adhesion.

PMID- 17202860
TI  - The complete mitochondrial genome of Pollicipes mitella (Crustacea, Maxillopoda,
      Cirripedia): non-monophylies of maxillopoda and crustacea.
AB  - The whole mitochondrial genome (14,915 nt) of Pollicipes mitella (Crustacea,
      Maxillopoda, Cirripedia, Thoracica) was sequenced and characterized. It is the
      shortest of the 31 completely sequenced crustacean mitochondrial genomes, with
      the exception of a copepod Tigriopus japonicus (14,628 nt). It consists of the
      usual 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 relatively
      short non-coding region (294 nt). The thoracican cirripeds apart from Megabalanus
      volcano have the same arrangement of protein-coding genes as Limulus polypemus,
      but there are frequent tRNA gene translocations (at least 8). Some interesting
      translocation features that may be specific to the thoracican cirriped lineage
      are as follows: 1) trnK-trnQ lies between the control region and trnI, 2) trnA
      trnE lies between trnN and trnS1, 3) trnP lies between ND4L and trnT, and 4) trnY
      trnC lies between trnS2 and ND1. In P. mitella there are two trnL genes (L1 and
      L2) in the typical crustacean positions (ND1-L1-LrRNA and CO1-L2-CO2). The
      present result is compared and discussed with the other three cirriped
      mitochondrial genomes from one pedunculate (Pollicipes polymerus) and two
      sessiles (Tetraclita japonica and M. volcano) published so far. Mitochondrial
      protein phylogenies reconstructed by the BI and ML algorithms show that the
      thoracican Cirripedia is monophyletic (BPP 100/BP 100) and associated with
      Remipedia (BPP 98/BP 35). In addition, Oligostraca, including Ostracoda,
      Branchiura, and Pentastomida, is a monophyletic group (BPP 99/BP 68), and is
      basal to all the other examined arthropods. Remipedia + Cirripedia appears as an
      independent lineage within Arthropoda, apart from Thoracopoda (Malacostraca,
      Branchiopda, and Cephalocarida). The Thoracopoda is paraphyletic to Hexapoda. The
      present result suggests that the monophylies of Crustacea and Maxillopoda should
      be reconsidered.

PMID- 17202861
TI  - DNA barcoding Korean birds.
AB  - DNA barcoding, an inventory of DNA sequences from a standardized genomic region,
      provides a bio-barcode for identifying and discovering species. Several recent
      studies suggest that the sequence diversity in a 648 bp region of the
      mitochondrial gene for cytochrome c oxi- dase I (COI) might serve as a DNA
      barcode for identify- ing animal species such as North American birds, in- sects
      and fishes. The present study tested the effective- ness of a COI barcode in
      discriminating Korean bird species. We determined the 5' terminus of the COI bar-
      code for 92 species of Korean birds and found that spe- cies identification was
      unambiguous; the genetic differ- ences between closely related species were, on
      average, 25 times higher than the differences within species. We identified only
      one misidentified species out of 239 specimens in a genetic resource bank, so
      confirming the accuracy of species identification in the banking system. We also
      identified two potential composite species, calling for further investigation
      using more samples. The finding of large COI sequence differences between species
      confirms the effectiveness of COI barcodes for identifying Korean bird species.
      To bring greater reliability to the identification of species, increased in- tra-
      and interspecies sampling, as well as supplementa- tion of the mitochondrial
      barcodes with nuclear ones, is needed.

PMID- 17202862
TI  - Effects of recombinant imperatoxin A (IpTxa) mutants on the rabbit ryanodine
      receptor.
AB  - Imperatoxin A (IpTxa), a 3.7 kDa peptide from the African scorpion Pandinus
      imperator, is an agonist of the skeletal muscle ryanodine receptor (RyR1). In
      order to study the structure of the toxin and its effect on RyR1, IpTxa cDNA was
      PCR-amplified using 3 pairs of primers, and the toxin was expressed in E. coli.
      The toxin was further purified by chromatography, and various point mutants in
      which basic amino acids were substituted by alanine were prepared by site
      directed mutagenesis. Studies of single channel properties by the planar lipid
      bilayer method showed that the recombinant IpTxa was identical to the synthetic
      IpTxa with respect to high-performance liquid chromatography mobility, amino acid
      composition and specific effects on RyR1. Mutations of certain basic amino acids
      (Lys19, Arg23, and Arg33) dramatically reduced the capacity of the peptide to
      activate RyRs. A subconductance state predominated when Lys8 was substituted with
      alanine. These results suggest that some basic amino acid residues in IpTxa are
      important for activation of RyR1, and that Lys8 plays an important role in
      regulating the gating mode of RyR1.

PMID- 17202863
TI  - Determination of neurotoxin gene expression in Clostridium botulinum type A by
      quantitative RT-PCR.
AB  - Real time reverse transcription (RT)-PCR was used to quantify the expression of
      the botulinum neurotoxin type A (BoNT/A) gene (cntA) by normalization with the
      expression of 16S rRNA. The method were confirmed by monitoring the mRNA levels
      of cntA during growth in five type A strains. In all but one of the strains the
      expression of cntA mRNA was maximal in the late exponential phase, and
      approximately 35-fold greater than in the early exponential phase. The
      concentration of the extracellular BoNT/A complex detected by ELISA was highest
      in stationary phase. Sodium nitrite and sorbic acid completely inhibited growth
      at 20 ppm and 4 mg ml-1, respectively. CntA expression became lower in proportion
      to the concentration of sorbic acid, and this reduction was confirmed by mouse
      bioassay. Our results show that real time RT-PCR can be used to quantify levels
      of C. botulinum type A neurotoxin transcripts and to assess the effects of food
      additives on botulinal risk.

PMID- 17202864
TI  - Isolation of new CHO cell mutants defective in CMP-sialic acid biosynthesis and
      transport.
AB  - Sialic acid is a sugar typically found at the N-glycan termini of glycoproteins
      in mammalian cells. Lec3 CHO cell mutants are deficient in epimerase activity,
      due to a defect in the gene that encodes a bifunctional UDP-GlcNAc 2
      epimerase/ManNAc kinase (GNE). Sialic acid modification on the cell surface is
      partially affected in these cells. We have mutagenized Lec3 CHO cells and
      isolated six mutants (termed C2m) deficient in the cell surface expression of
      polysialic acid (PSA). Mutant C2m9 was partially defective in expression of cell
      surface PSA and wheat germ agglutinin (WGA) binding, while in the other five
      mutants, both cell-surface PSA and WGA binding were undetectable. PSA expression
      was restored by complementation with the gene encoding the CMP-sialic acid
      transporter (CST), indicating that CST mutations were responsible for the
      phenotypes of the C2m cells. We characterized the CST mutations in these cells by
      Northern blotting and RT-PCR. C2m9 and C2m45 carried missense mutations resulting
      in glycine to glutamate substitutions at amino acids 217 (G217E) and 256 (G256E),
      respectively. C2m13, C2m39 and C2m31 had nonsense mutations that resulted in
      decreased CST mRNA stability, and C2m34 carried a putative splice site mutation.
      PSA and CD15s expression in CST-deficient Lec2 cells were partially rescued by
      G217E CST, but not by G256E CST, although both proteins were expressed at similar
      levels, and localized to the Golgi. These results indicate that the novel
      missense mutations isolated in this study affect CST activity.

PMID- 17202865
TI  - BMP-2-enhanced chondrogenesis involves p38 MAPK-mediated down-regulation of Wnt
      7a pathway.
AB  - The bone morphogenetic protein (BMP) family has been implicated in control of
      cartilage development. Here, we demonstrate that BMP-2 promotes chondrogenesis by
      activating p38 mitogen-activated protein kinase (MAPK), which in turn
      downregulates Wnt-7a/b-catenin signaling responsible for proteasomal degradation
      of Sox9. Exposure of mesenchymal cells to BMP-2 resulted in upregulation of Sox9
      protein and a concomitant decrease in the level of b-catenin protein and Wnt-7a
      signaling. In agreement with this, the interaction of Sox9 with b-catenin was
      inhibited in the presence of BMP-2. Inhibition of the p38 MAPK pathway using a
      dominant negative mutant led to sustained Wnt-7a signaling and decreased Sox9
      expression, with consequent inhibition of precartilage condensation and
      chondrogenic differentiation. Moreover, overexpression of b-catenin caused
      degradation of Sox9 via the ubiquitin/26S proteasome pathway. Our results
      collectively indicate that the increase in Sox9 protein resulting from
      downregulation of b-catenin/Wnt-7a signaling is mediated by p38 MAPK during BMP-2
      induced chondrogenesis in chick wing bud mesenchymal cells.

PMID- 17202866
TI  - Formation of a new solo-LTR of the human endogenous retrovirus H family in human
      chromosome 21.
AB  - Human endogenous retroviruses (HERVs) contribute to various kinds of genomic
      instability via rearrangement and retrotransposition events. In the present study
      the formation of a new human-specific solo-LTR belonging to the HERV-H family
      (AP001667; chromosome 21q21) was detected by a comparative analysis of human
      chromosome 21 and chimpanzee chromosome 22. The solo-LTR was formed as a result
      of an equal homologous recombination excision event. Several evolutionary
      processes have occurred at this locus during primate evolution, indicating that
      mammalian-wide interspersed repeat (MIR) and full-length HERV-H elements
      integrated into hominoid genomes after the divergence of Old World monkeys and
      hominoids, and that the solo-LTR element was created by recombination excision of
      the HERV-H only in the human genome.

PMID- 17202867
TI  - Maternal smoking and environmental tobacco smoke exposure and the risk of
      orofacial clefts.
AB  - BACKGROUND: Smoking during pregnancy has been associated with orofacial clefts in
      numerous studies. However, most previous studies have not been able to assess the
      relation between maternal smoking and specific phenotypes (eg, bilateral clefts).
      METHODS: We examined the association between periconceptional maternal smoking,
      environmental tobacco smoke (ETS) exposure, and cleft lip with or without cleft
      palate (CLP) (n = 933) and cleft palate only (CPO) (n = 528) compared with
      infants with no major birth defects (n = 3390). Infants were born between 1
      October 1997 and 31 December 2001, and exposures were ascertained from maternal
      telephone interviews for the National Birth Defects Prevention Study. We excluded
      infants who had a first-degree relative with an orofacial cleft. Effect estimates
      were adjusted for folic acid use, study site, prepregnancy obesity, alcohol use,
      gravidity, and maternal age, education, and race/ethnicity. RESULTS:
      Periconceptional smoking was associated with CLP (odds ratio = 1.3; 95%
      confidence interval = 1.0-1.6), and more strongly associated with bilateral CLP
      (1.7; 1.2-2.6), with a weaker association observed for CPO. Heavy maternal
      smoking (25+ cigarettes/day) was associated with CLP (1.8; 1.0-3.2), bilateral
      CLP (4.2; 1.7-10.3), and CPO with Pierre Robin sequence (2.5; 0.9-7.0). ETS
      exposure was not associated with CLP or CPO. CONCLUSIONS: This study confirmed
      the modest association between smoking and orofacial clefts that has been
      consistently reported, and identified specific phenotypes most strongly affected.

PMID- 17202868
TI  - Variation in incidence of neurodevelopmental disorders with season of birth.
AB  - BACKGROUND: The etiologies of autism spectrum disorder and many
      neurodevelopmental disorders are largely unknown. The detection of a seasonal
      variation of birth of children diagnosed with a certain disorder could suggest
      etiological factors that follow a seasonal pattern. We examined the seasonal
      variation of births of children diagnosed with any of 4 common childhood
      neuropsychiatric disorders: autism spectrum disorder, hyperkinetic disorder,
      Tourette syndrome, and obsessive-compulsive disorder. METHODS: The study cohort
      consisted of all children born in Denmark from 1990 through 1999 identified in
      the Danish Medical Birth Register (n = 669,995). Outcome data consisted of both
      inpatient and outpatient diagnoses reported to the Danish National Psychiatric
      Registry from 1995 through 2004 using the International Classification of
      Diseases, 10th edition, diagnostic coding system. Logistic regression combined
      with spline (a smoothing method) was used to estimate the variation with season
      of birth for each disorder. Estimates of risk of each disorder with season of
      birth were adjusted for differences in follow-up time and change in incidence
      over time. RESULTS: No convincing variations in season of birth were observed for
      any of the 4 disorders, or for the autism-spectrum-disorder subtypes. CONCLUSION:
      Although we cannot rule out the possibility of seasonal variation of birth for a
      range of childhood neurodevelopmental disorders, we find little evidence that
      seasonal environmental factors are related to these disorders.

PMID- 17202869
TI  - Cryptorchidism according to maternal gestational smoking.
AB  - BACKGROUND: It has been suggested that maternal smoking during pregnancy is a
      risk factor for low sperm counts and testicular cancer in the offspring.
      Cryptorchidism is associated with both of these disorders and might share causal
      mechanisms. METHODS: We used prospective information on prenatal exposures and
      obstetric information on the birth of 5716 boys, collected from 1984 to 1987.
      During the 16-19 years of follow-up, 270 cases of cryptorchidism were diagnosed,
      and 185 of these boys underwent orchiopexy. RESULTS: Compared with nonsmokers,
      the adjusted risk ratio for being diagnosed with cryptorchidism was 1.1 (95%
      confidence interval = 0.8-1.6) if the mothers smoked 10-19 cigarettes/day and 2.3
      (1.1-5.0) if they smoked > or = 20 cigarettes/day. The risk ratios for orchiopexy
      were 1.4 (0.9-2.1) and 1.8 (0.6-5.0), respectively. CONCLUSION: An excess risk of
      cryptorchidism was observed among sons of mothers who smoked 10 cigarettes or
      more per day during pregnancy. In recognition of the limited power of this study,
      the findings should be replicated in larger cohorts.

PMID- 17202870
TI  - Ambient manganese exposure is negatively associated with human sperm motility and
      concentration.
AB  - BACKGROUND: Occupational and experimental animal studies indicate that exposure
      to high levels of manganese impairs male fertility, but the effects of ambient
      manganese in humans are not known. METHODS: We measured blood levels of manganese
      and selenium in 200 infertility clinic clients in a cross-sectional study.
      Correlations between metals and semen variables were determined, adjusting for
      other risk factors. Outcomes were low motility (<50% motile), low concentration
      (<20 million/mL), or low morphology (<4% normal). We also investigated dose
      response relationships between quartiles of manganese exposure and sperm
      parameters. RESULTS: High manganese level was associated with increased risk of
      low sperm motility (odds ratio = 5.4; 95% confidence interval = 1.6-17.6) and low
      sperm concentration (2.4; 1.2-4.9). We saw a U-shaped dose-response pattern
      between quartiles of manganese exposure and all 3 sperm parameters. CONCLUSION:
      Ambient exposure to manganese levels is associated with a reduction in sperm
      motility and concentration. No adverse effects were seen for high selenium.

PMID- 17202871
TI  - Residential magnetic fields, medication use, and the risk of breast cancer.
AB  - BACKGROUND: Exposure to 60-Hz magnetic fields may increase breast cancer risk by
      suppressing the nocturnal production of melatonin. The use of medications
      associated with reduced melatonin levels could modify this relationship. METHODS:
      We recontacted participants in a population-based case-control study of
      residential magnetic field exposure and breast cancer risk and interviewed them
      regarding medication use during the 10 years before diagnosis. Cases were
      diagnosed between November 1992 and March 1995, and magnetic field levels were
      measured in the home at diagnosis. We obtained medication use information by
      telephone interview from 558 cases and 588 controls. RESULTS: Breast cancer risk
      was not associated with exposure to residential magnetic fields, regardless of
      medication use. CONCLUSIONS: These results support previous findings that
      magnetic field exposure does not increase breast cancer risk.

PMID- 17202872
TI  - Women's health during mid-life survey: the use of complementary and alternative
      medicine by symptomatic women transitioning through menopause in Sydney.
AB  - OBJECTIVE: To survey the extent of complementary and alternative medicine (CAM)
      use among women for the alleviation of menopausal symptoms. DESIGN: A total of
      1,296 eligible women aged 45 to 65 years were recruited from three Sydney
      menopause clinics, general practice clinics, and government agencies between July
      2003 and July 2004. Volunteers were invited to complete a 19-item questionnaire
      covering basic demographics, general health status, use of CAM therapies and
      products, use of pharmaceuticals, and sources of CAM advice. RESULTS: Of
      respondents, 53.8% had visited a CAM practitioner and/or used a CAM product
      during the past year, with 34% using a product only and 5% consulting a
      practitioner only. The most commonly visited practitioners were naturopaths
      (7.2%) and acupuncturists (4.8%), whereas the most popular products were soy
      (25.4%) and evening primrose oil (18.4%). Massage, chiropractic, and nutrition
      were rated the most effective therapies, and phytoestrogen tablets, evening
      primrose oil, and black cohosh were deemed the most effective products. Of the
      59.9% of respondents currently using prescription or over-the-counter
      pharmaceuticals, 62.5% reported using CAM products during the past 12 months. Of
      CAM users 71% had informed their doctor about CAM use, whereas 26.4% of
      respondents reported their doctor had inquired about CAM use. CONCLUSIONS: CAM
      use by women to alleviate menopausal symptoms is common, with several therapies
      perceived to be effective. Although a significant proportion of women may use CAM
      in conjunction with pharmaceuticals, relevant communication between medical
      practitioners and patients remains inadequate and may expose the patient to
      potential drug-herb interactions.

PMID- 17202873
TI  - Simple truths about America's uninsured.
AB  - Nurses deal with the fallout of a nation with more than 46 million uninsured.
      Affecting the patients and families they care for, the hospitals and clinics they
      work in and manage, and the communities they serve, nurses have a credible
      standing from which to debunk any myths about who the uninsured are, why they are
      uninsured, and the difference that health insurance makes in their health and
      well-being. This article on the uninsured and health insurance coverage among low
      income Americans outlines key facts about the uninsured and the primary cause of
      the problem--the affordability of health insurance.

PMID- 17202874
TI  - Reduction in head and intervertebral motion provided by 7 contemporary cervical
      orthoses in 45 individuals.
AB  - STUDY DESIGN: Biomechanical evaluation of cervical orthoses. OBJECTIVE: To
      provide data to help clinicians select an orthosis for immobilization of the
      adult cervical spine. SUMMARY OF BACKGROUND DATA: There are limited data on the
      effectiveness of cervical orthoses at restricting intervertebral motion, and many
      of the commonly used, contemporary braces have not been evaluated. Additionally,
      no data exist comparing the effectiveness of braces in the supine versus the
      upright position. New technology is available to measure intervertebral motion
      with greater accuracy. METHODS: Overall range of motion of the head in 3 planes
      as well as intervertebral motion in the sagittal plane were measured in 45
      healthy adult volunteers while wearing 7 cervical orthoses. Subject-reported
      comfort of each brace was also recorded. RESULTS: All braces significantly
      reduced intervertebral motion. Effectiveness and comfort varied between braces.
      In general, orthoses could be grouped as cervical braces or cervicothoracic
      braces. The latter was consistently better at limiting motion, with some
      differences within these groups as well. CONCLUSION: These data will help to
      guide the clinician in selecting the appropriate cervical orthosis for their
      adult patient based on comfort, morphologic considerations, and degree of
      immobilization required.

PMID- 17202875
TI  - Locomotor skills and balance strategies in adolescents idiopathic scoliosis.
AB  - STUDY DESIGN: Locomotor balance control assessment was performed to study the
      effect of idiopathic scoliosis on head-trunk coordination in 17 patients with
      adolescent idiopathic scoliosis (AIS) and 16 control subjects. OBJECTIVE: The aim
      of this study was to explore the functional effects of structural spinal
      deformations like idiopathic scoliosis on the balance strategies used during
      locomotion. SUMMARY OF BACKGROUND DATA: Up to now, the repercussion of the
      idiopathic scoliosis on head-trunk coordination and balance strategies during
      locomotion is relatively unknown. METHODS: Seventeen patients with AIS (mean age
      14 years 3 months, 10 degrees < Cobb angle > 30 degrees) and 16 control subjects
      (mean age 14 years 1 month) were tested during various locomotor tasks: walking
      on the ground, walking on a line, and walking on a beam. Balance control was
      examined in terms of rotation about the vertical axis (yaw) and on a frontal
      plane (roll). Kinematics of foot, pelvis, trunk, shoulder, and head rotations
      were measured with an automatic optical TV image processor in order to calculate
      angular dispersions and segmental stabilizations. RESULTS: Decreasing the walking
      speed is the main adaptive strategy used in response to balance problems in
      control subjects as well as patients with AIS. However, patients with AIS
      performed walking tasks more slowly than normal subjects (around 15%). Moreover,
      the pelvic stabilization is preserved, despite the structural changes affecting
      the spine. Lastly, the biomechanical defect resulting from idiopathic scoliosis
      mainly affects the yaw head stabilization during locomotion. CONCLUSIONS:
      Patients with AIS show substantial similarities with control subjects in adaptive
      strategies relative to locomotor velocity as well as balance control based on
      segmental stabilization. In contrast, the loss of the yaw head stabilization
      strategies, mainly based on the use of vestibular information, probably reflects
      the presence of vestibular deficits in the patients with AIS.

PMID- 17202876
TI  - Superficial lumbopelvic muscle overactivity and decreased cocontraction after 8
      weeks of bed rest.
AB  - STUDY DESIGN: Longitudinal study. OBJECTIVE: To gain insight into the effects of
      inactivity on lumbopelvic stabilization. SUMMARY OF BACKGROUND DATA: Some authors
      have suggested a link between inactivity and lumbopelvic (LP) pain. Studies
      examining the superficial musculature in LP pain have shown overactivity and
      increased cocontraction. Studies in inactivity (bed rest, microgravity) have
      shown similar effects on the musculature of the legs. Here we examine the effect
      of bed rest on superficial LP activity and cocontraction. METHODS: Ten male
      subjects participated in the "Berlin Bed Rest Study" and underwent 8 weeks of bed
      rest with a 1-year follow-up. A repetitive knee movement model at four movement
      speeds in non-weightbearing was used to assess, via electromyography, activity
      (amplitude-ratios) in five superficial LP muscles and abdominal flexor-lumbar
      extensor cocontraction for LP stabilization. Testing was conducted at regular
      intervals during and after bed rest. RESULTS: Analysis of the amplitude-ratio
      data showed a significant effect of testing date (F = 2.38, P = 0.005). This
      effect was generalized across all muscles, however (F = 0.59, P = 0.989). During
      bed rest, subjects exhibited higher levels of activity but lower levels of
      cocontraction (F = 8.84, P < 0.001), and the changes were still present up to 1
      year after bed rest. CONCLUSIONS: The bed rest protocol resulted in the
      development of superficial muscle overactivity but decreased cocontraction. These
      changes could reflect dysfunction of central nervous system control of LP
      stabilization. These changes were still apparent 1 year after bed rest,
      suggesting a stable change in motor control.

PMID- 17202877
TI  - Safe atlantoaxial fixation using a laminar screw (intralaminar screw) in a
      patient with unilateral occlusion of vertebral artery: case report.
AB  - STUDY DESIGN: A case of atlantoaxial fusion using an intralaminar (unilateral
      crossing laminar screw) screw is presented in a patient with unilateral vertebral
      artery communication with the basilar artery. OBJECTIVES: To document the
      significance of the intralaminar screw technique in the aforementioned case.
      SUMMARY OF BACKGROUND DATA: Vertebral artery injury is directly linked with
      intraoperative or perioperative death if the vertebral artery communicates only
      unilaterally to the basilar artery or has an obvious dominant side. In this
      situation, irrespective of whether the pedicle is confirmed to be sufficient for
      pedicle screw placement, if the vertebral artery is violated, fatal complications
      will occur. The literature reports that even proficient surgeons cannot guarantee
      100% accuracy in pedicle screw placement. The intralaminar screw technique is
      currently the safest with regard to avoiding violation of the vertebral artery.
      Biomechanical studies have also shown this technique to ensure sufficient
      strength. METHODS: The patient had rheumatoid atlantoaxial subluxation, and the
      right vertebral artery alone communicated with basilar artery, while the left
      ended blind. She underwent atlantoaxial fixation with an intralaminar screw
      (unilateral-crossing laminar screw) of the axis and lateral mass atlas screws
      inserted via the posterior arch. RESULTS: The intralaminar screw (unilateral
      crossing laminar screw) was completed, and comprised lateral mass atlas screws
      and rods. There were no complications during and after surgery. Good bone union
      was achieved. CONCLUSION: Patients with unilateral dominant vertebral artery are
      good candidates for the intralaminar screw technique, even if the pedicle anatomy
      is sufficient to insert pedicle screws.

PMID- 17202878
TI  - Posterior cervical arthrodesis for subacute odontoid fracture in a patient with
      osteopetrosis: case report.
AB  - STUDY DESIGN: A case of subacute odontoid fracture in a patient with
      osteopetrosis treated with posterior cervical arthrodesis using transarticular
      screws and interspinous wiring. OBJECTIVES: To report the first successful
      cervical arthrodesis in a patient with osteopetrosis and to highlight the
      potential perioperative pitfalls in this rare surgical population. SUMMARY OF
      BACKGROUND DATA: Osteopetrosis is a group of skeletal dysplasias characterized by
      osteoclast dysfunction, impaired bone resorption, and poor bone remodeling.
      Unique challenges associated with surgical fixation in osteopetrotic bone include
      a high incidence of nonunion, intraoperative fractures, intraoperative
      instrumentation failure, infection, and prosthesis loosening. We report the case
      of a patient with a subacute odontoid fracture treated successfully with
      posterior cervical arthrodesis using transarticular screws and interspinous
      wiring. METHODS: The surgical technique, intraoperative pitfalls, and 2-year
      follow-up data are reported. RESULTS: The patient underwent a successful
      posterior cervical arthrodesis using transarticular screws and interspinous
      wiring with autogenous iliac crest graft. At 2 years, a stable fixation was
      achieved with only mild postoperative limitation in neck range of motion.
      CONCLUSIONS: Cervical fractures and instability that require surgery in patients
      with osteopetrosis represent a unique challenge to the orthopedic spine surgeon.
      Despite the increased potential for perioperative instrumentation complications,
      nonunion, and infection, posterior cervical arthrodesis can be achieved and
      should be considered in the treatment armamentarium for this potentially
      catastrophic injury.

PMID- 17202879
TI  - Surgical treatment of cervical kyphosis in Larsen syndrome: report of 3 cases and
      review of the literature.
AB  - STUDY DESIGN: A retrospective case series. OBJECTIVE: To review the surgical
      results for midcervical kyphosis in 3 cases with Larsen syndrome, and to discuss
      the choice of surgical treatments. SUMMARY OF BACKGROUND DATA: Cervical kyphosis
      is the most hazardous and serious manifestation of Larsen syndrome due to the
      risk of life-threatening paralysis, and thus usually requires surgical treatment.
      However, little information has been reported concerning surgical treatments for
      this challenging condition. METHODS: Three patients with Larsen syndrome were
      surgically treated for midcervical kyphosis at our institution. RESULTS: An
      infant with mild cervical kyphosis was successfully treated with posterior
      arthrodesis using a halo immobilization, and anterior vertebral growth with a
      mature posterior fusion mass resulted in spontaneous correction of the kyphosis.
      In the remaining 2 infants with myelopathic symptoms due to severe and structural
      kyphosis, anterior decompression and fusion via a lateral approach followed by
      posterior fusion with segmental spinal instrumentation and halo immobilization
      resulted in improved neurologic symptoms and solid fusion. CONCLUSIONS: Posterior
      spinal fusion is only indicated for patients with mild and flexible cervical
      kyphosis, and anterior decompression and circumferential arthrodesis is required
      for patients with severe kyphotic deformity, who usually develop myelopathic
      symptoms. Anterior surgery for such a small patient with severe kyphosis involves
      much higher risk of spinal cord injury during decompression maneuvers and
      difficulty in stabilization of the reconstructed cervical spine. Therefore, all
      patients with Larsen syndrome should be screened with radiographs at the first
      visit to detect cervical kyphosis early so that posterior alone fusion is
      possible.

PMID- 17202880
TI  - Primary solitary cervical amyloidosis: case report and review of the literature.
AB  - STUDY DESIGN: A case report and literature review are presented. OBJECTIVE: To
      describe and review the clinical presentations, characteristic findings from
      imaging studies, types, differential diagnosis, prognosis, and treatment of
      amyloidoma arising within the vertebrae. SUMMARY OF BACKGROUND DATA: Amyloidoma
      can occur in the bone, skin, larynx, lymph nodes, urinary bladder, eye, tongue,
      and gastrointestinal system. However, amyloidomas affecting the vertebral bones
      are very rare. To our knowledge, only 3 cases of amyloidoma involving cervical
      spine have been reported previously. METHODS: In this report, we present a case
      of solitary amyloidosis of the cervical spine. RESULTS: The differential
      diagnosis of primary solitary spinal amyloidoma includes metastasis, infection,
      primary bone tumors, plasmocytoma, and Potts abscess. The correct diagnosis can
      be achieved only after the specific staining of tissue. The prognosis of
      amyloidosis is related to the specific form of amyloidosis. However, primary
      solitary amyloidosis has the best prognosis, although a limited number of
      patients without long-term follow-up studies have been reported. CONCLUSIONS:
      Primary solitary amyloidosis is a rare form of the amyloidosis, which is
      different from the other forms of amyloidosis because of excellent prognosis with
      surgical excision. Combined surgical excision and spinal stabilization is the
      best treatment.

PMID- 17202881
TI  - A rare case of cavernous lymphangioma in the epidural space of the
      cervicothoracic spine.
AB  - STUDY DESIGN: A case report. OBJECTIVES: To report and discuss a case of
      lymphangioma in the epidural space of the cervicothoracic spine. SUMMARY OF
      BACKGROUND DATA: Lymphangioma of the soft tissue is not uncommon, but
      lymphangiomas presenting as a spinal soft tissue tumor in the epidural space are
      extremely rare. METHODS: A 61-year-old woman with pain and numbness in the left
      arm. Magnetic resonance imaging demonstrated a half ring-shaped soft tissue mass
      in the left epidural space from the C6 to T1 level. The patient underwent
      osteoplastic laminectomy from C6 to T1. Histopathologic diagnosis of the resected
      tumor was cavernous lymphangioma. RESULTS: One year after the operation, the
      patient reported mild pain in left upper limb, but there was no evidence of local
      recurrence on magnetic resonance imaging. CONCLUSION: To the authors' knowledge,
      this is an extremely rare reported case of lymphangioma presenting as a spinal
      soft tissue tumor in the cervicothoracic epidural space. Further observation is
      recommended because of the possibility of local recurrence.

PMID- 17202882
TI  - Infantile lumbosacral spinal subdural abscess with sacral dermal sinus tract.
AB  - STUDY DESIGN: Clinical case report of a spinal subdural abscess in an infant
      presenting with sacral dermal sinus tract (DST). OBJECTIVES: To suggest that
      sacral DST with caudal direction may require surgical resection as early as
      possible. SUMMARY OF BACKGROUND DATA: DST may induce the formation of a spinal
      abscess. However, it is sometimes difficult to decide on early surgical resection
      for DST, especially in cases that are located at a lower level than the lumbar
      spine and directed caudally that is not accompanied by cerebrospinal fluid
      leakage. METHODS: A 9-month-old girl was transferred due to intermittent fever
      and vomiting, with the midline sinus of the lower back at the second sacral
      spinal level. She showed mild tenderness of the lower back and slight weakness of
      both lower extremities with increased residual urine volume of the bladder.
      Magnetic resonance imaging (MRI) showed that the low-lying sacral DST traced into
      the subdural space with caudal orientation, and the presence of extensive
      subdural spinal abscess from the first lumbar spine to the fourth sacrum.
      RESULTS: Emergency resection of the sacral DST was performed after laminotomy
      from the first lumbar spine to the second sacrum, and the subdural spinal abscess
      was also surgically removed. After 8 weeks of intravenous antibiotic treatment,
      she showed no neurologic deficit and no evidence of residual abscess on MRI.
      CONCLUSION: We suggest that even low-lying sacral DST may require surgical
      resection as early as possible because it may result in indolent and extensive
      spinal abscesses.

PMID- 17202883
TI  - Failure properties of cervical spinal ligaments under fast strain rate
      deformations.
AB  - STUDY DESIGN: The failure responses of the anterior longitudinal ligament,
      posterior longitudinal ligament, and ligamentum flavum were examined in vitro
      under large strain-rate mechanical loading. OBJECTIVE: To quantify the failure
      properties for 3 cervical spinal ligaments at strain rates associated with
      traumatic events. SUMMARY OF BACKGROUND DATA: There exists little experimentation
      literature for fast-rate loading of the cervical spine ligaments. The small
      amount of available information is framed only in extensive experimental
      coordinates, and not in the context of strains. METHODS: Bone-ligament-bone
      complexes were strained at fast rates, in an incrementally increasing loading
      protocol using a servohydraulic mechanical test frame. Failure loads and
      displacements were converted to engineering and true stress and strain values,
      and compared for the different ligaments (anterior longitudinal ligament,
      posterior longitudinal ligament, and ligamentum flavum), spinal levels (C3-C4, C5
      C6, and C7-T1), and for male versus female specimens. RESULTS: There were no
      significant differences in force or true stress for gender or spinal level. There
      was a significant difference in force and true stress for ligament type. A
      difference was found between the posterior longitudinal ligament and ligamentum
      flavum for failure force, and between the ligamentum flavum and both the anterior
      and posterior longitudinal ligaments for failure true stress. No significant
      differences were found in true strain for ligament, gender, or spinal level. The
      mean ligament failure true strain was 0.81. Failure true strains were
      approximately 57% of the failure engineering strains. CONCLUSIONS: Once the
      injury mechanisms of the cervical spine are fully understood, computational
      models can be employed to understand the potentially traumatic effects of
      clinical procedures, and mitigate injury in impact, falls, and other high-rate
      scenarios. The soft tissue failure properties in this study can be used to
      develop failure tolerances in fast-rate loading scenarios. Failure properties of
      the anterior and posterior longitudinal ligaments were similar, and the same
      properties can be used to model both ligaments.

PMID- 17202885
TI  - Surgical or nonoperative treatment for lumbar spinal stenosis? A randomized
      controlled trial.
AB  - STUDY DESIGN: A randomized controlled trial. OBJECTIVES: To assess the
      effectiveness of decompressive surgery as compared with nonoperative measures in
      the treatment of patients with lumbar spinal stenosis. SUMMARY OF BACKGROUND
      DATA: No previous randomized trial has assessed the effectiveness of surgery in
      comparison with conservative treatment for spinal stenosis. METHODS: Four
      university hospitals agreed on the classification of the disease, inclusion and
      exclusion criteria, radiographic routines, surgical principles, nonoperative
      treatment options, and follow-up protocols. A total of 94 patients were
      randomized into a surgical or nonoperative treatment group: 50 and 44 patients,
      respectively. Surgery comprised undercutting laminectomy of the stenotic segments
      in 10 patients augmented with transpedicular fusion. The primary outcome was
      based on assessment of functional disability using the Oswestry Disability Index
      (scale, 0-100). Data on the intensity of leg and back pain (scales, 0-10), as
      well as self-reported and measured walking ability were compiled at randomization
      and at follow-up examinations at 6, 12, and 24 months. RESULTS: Both treatment
      groups showed improvement during follow-up. At 1 year, the mean difference in
      favor of surgery was 11.3 in disability (95% confidence interval [CI], 4.3-18.4),
      1.7 in leg pain (95% CI, 0.4-3.0), and 2.3(95% CI, 1.1-3.6) in back pain. At the
      2-year follow-up, the mean differences were slightly less: 7.8 in disability (95%
      CI, 0.8-14.9) 1.5 in leg pain (95% CI, 0.3-2.8), and 2.1 in back pain (95% CI,
      1.0-3.3). Walking ability, either reported or measured, did not differ between
      the two treatment groups. CONCLUSIONS: Although patients improved over the 2-year
      follow-up regardless of initial treatment, those undergoing decompressive surgery
      reported greater improvement regarding leg pain, back pain, and overall
      disability. The relative benefit of initial surgical treatment diminished over
      time, but outcomes of surgery remained favorable at 2 years. Longer follow-up is
      needed to determine if these differences persist.

PMID- 17202886
TI  - Galectin-3 expression in the intervertebral disc: a useful marker of the
      notochord phenotype?
AB  - STUDY DESIGN: Galectin-3 expression in rat intervertebral disc at different
      stages in postnatal life is evaluated. OBJECTIVE: To determine if galectin-3
      expression is confined to cells of the nucleus pulposus in the postnatal rat
      intervertebral disc. SUMMARY OF BACKGROUND DATA: During embryonic development,
      the anulus fibrosus is derived from the sclerotome, whereas the nucleus pulposus
      is notochordal. Many authorities opine that in the postnatal disc, notochordal
      cells play a central role in controlling the development of degenerative disc
      disease. Surprisingly, unequivocal evidence supporting the existence of
      notochordal cells in the nucleus pulposus in postnatal life has yet to be
      demonstrated. Since the expression of galectin-3 is commonly used to identify
      notochordal cells, we evaluated its expression in tissues of the rat disc and in
      cultured cells. METHODS: Galectin-3 expression was studied in the nucleus
      pulposus and anulus fibrosus tissue of rat discs (2 days, 9 weeks, and 10 months
      old), and cultured cells using different biochemical and molecular biology
      methods. Rat sternal cartilage and cultured sternal chondrocytes were used as
      controls. RESULTS: Immunohistochemical studies indicated that galectin-3 was
      present in the nucleus pulposus and anulus fibrosus. In both discal tissues and
      cultured cells, studies confirmed that there was a robust expression of galectin
      3 messenger ribonucleic acid and protein. Protein expression patterns were
      similar in neonatal, young, and mature rats. There was also evidence of
      intracellular and membrane expression of galectin-3 in the cultured disc cells.
      Finally, significant levels of galectin-3 were evident in rat sternal cartilage
      and cultured sternal chondrocytes. CONCLUSIONS: Results of the study indicate
      that galectin-3 is expressed in the neonatal, young, and mature rat disc, and its
      expression is not restricted to the cells of the nucleus pulposus. Because of its
      ubiquitous expression, this protein cannot be used as a marker of notochordal
      cells in the postnatal rat disc.

PMID- 17202887
TI  - Stab incision for inducing intervertebral disc degeneration in the rat.
AB  - STUDY DESIGN: The degenerative response of rat tail and lumbar intervertebral
      discs to a stab incision was evaluated. OBJECTIVE: To examine and compare the
      postinjury degenerative response of lumbar and tail discs. SUMMARY OF BACKGROUND
      DATA: Although successful in larger animals, a stab incision for inducing disc
      degeneration in rats has not been evaluated. Rodents are desirable models for
      disc repair studies due to their low cost, ease of care, and fast healing times.
      METHODS: Lumbar and tail discs were exposed surgically and stabbed with a number
      11 blade. Disc architecture, levels of IL-1beta, IL-6, and TNF-alpha, and
      biomechanical properties were analyzed. A functional disability secondary to
      multilevel lumbar disc injury was quantified and compared with that of rats
      undergoing sham surgery. RESULTS: Histologic evaluation of stabbed tail discs
      demonstrated a nucleus pulposus size decrease, anular collagen layer
      disorganization, and cellular metaplasia of anular fibroblasts to chondrocyte
      appearing cells. Besides the continued presence of the stab injury tract, few
      changes were observed in the lumbar disc histology. Cytokine measurements
      indicated a transient peak in IL-1beta in tail discs 4 days following injury. No
      significant changes in IL-1beta, IL-6, or TNF-alpha were measured. No significant
      differences in biomechanical properties were observed between stab injury and
      sham surgery discs. Yet, despite insignificant differences in histologic,
      cytochemical, or biomechanical properties in the lumbar discs, the rats with
      lumbar stab injury had a significant decrease in walking ability 28 days after
      surgery. CONCLUSIONS: Tail disc stab injury was successful in creating
      morphologic signs of degeneration and transient high concentrations of IL-1beta.
      However, the degenerative response in the lumbar discs was much slower,
      suggesting that site-specific factors, such as increased stability due to
      posterior elements and torso musculature, helped facilitate healing. Yet,
      functional assessment indicated that the rats were partially disabled by multiple
      lumbar injuries.

PMID- 17202888
TI  - Q89R polymorphism in the LDL receptor-related protein 5 gene is associated with
      spinal osteoarthritis in postmenopausal Japanese women.
AB  - STUDY DESIGN: An association study investigating the genetic etiology for spinal
      osteoarthritis. OBJECTIVE: To determine the association of single-nucleotide
      polymorphism (SNP) causing an amino-acid change (Q89R) in the low-density
      lipoprotein receptor-related protein 5 (LRP5) coding region with spinal
      osteoarthritis. SUMMARY OF BACKGROUND DATA: Wnt/beta-catenin signaling pathway
      regulates bone density through a Wnt coreceptor LRP5. This pathway is also
      involved in cartilage development and homeostasis, suggesting that genetic
      variation in LRP5 gene may affect the pathogenesis of cartilage-related diseases,
      such as osteoarthritis. METHODS: We evaluated the presence of osteophytes,
      endplate sclerosis, and narrowing of disc spaces in 357 Japanese postmenopausal
      women. Missense coding SNP for Q89R of LRP5 gene was determined using TaqMan
      polymerase chain reaction (PCR) method. RESULTS: We found that subjects without
      the R allele (QQ; n = 321) had a significantly lower osteophyte formation score
      than did subjects bearing at least one R allele (QR + RR; n = 36) (7.80 vs.
      10.89, P = 0.0019 by analysis of covariance). CONCLUSIONS: We suggest that a
      genetic variation at the LRP5 gene locus is associated with spinal
      osteoarthritis, in line with the involvement of the LRP5 gene in the bone and
      cartilage metabolism.

PMID- 17202889
TI  - Role of tumor necrosis factor-alpha, interleukin-8, and dexamethasone in the
      focal adhesion kinase expression by human nucleus pulposus cells.
AB  - STUDY DESIGN: Human nucleus pulposus cells from intervertebral disc specimens
      were cultured to study the effects of tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-8 on the focal adhesion kinase (FAK) expression by these cells.
      The effect of co-stimulation with dexamethasone on the FAK expression by nucleus
      pulposus cells was also studied. OBJECTIVES: To evaluate the possible role of
      activated FAK expressed by the human nucleus pulposus cells and its correlation
      with inflammatory cytokines (TNF-alpha, IL-8) and dexamethasone. SUMMARY OF
      BACKGROUND DATA: There have been no reported studies showing the correlation
      between the activated FAK expression by human nucleus pulposus cells with
      inflammatory cytokines and dexamethasone. METHODS: The FAK expression in cultured
      human nucleus pulposus cells was studied, and Western blot and immunofluorescence
      analysis were performed to assess its relation to TNF-alpha, IL-8, and
      dexamethasone. RESULTS: Treatments of TNF-alpha and IL-8 up-regulated the
      activated FAK expression. Dexamethasone attenuated the cytokine-induced FAK
      expression. The effects of inflammatory cytokines on the FAK expression were
      found to be concentration dependent, with greater correlation shown by IL-8 than
      TNF-alpha. CONCLUSION: TNF-alpha and IL-8 stimulation up-regulated the FAK
      expression of human nucleus pulposus cells, and the coadministration of
      dexamethasone attenuated it.

PMID- 17202890
TI  - A bridging demineralized bone implant facilitates posterolateral lumbar fusion in
      New Zealand white rabbits.
AB  - STUDY DESIGN: Randomized controlled animal study. OBJECTIVE: Test the
      effectiveness of a single-strip demineralized bone matrix with hyaluronan and
      gelatin. SUMMARY OF BACKGROUND DATA: Demineralized bone matrix is widely used to
      augment spinal fusion, however, the effect of changing the physical
      characteristic and carrier is not known. METHODS: Demineralized bone matrix was
      extracted from the bones of New Zealand White rabbits, and combined with
      hyaluronan and gelatin to form solid strips. Forty-eight rabbits were randomized
      into a control and 2 experimental groups. In the control group, fusion was
      attempted with autograft bone. For group 2, demineralized bone matrix strips
      alone and for group 3, autograft and demineralized bone matrix strips were used.
      The fusion was assessed with manual manipulation and radiographs. The volume of
      the fusion mass was determined from computed tomographic images. RESULTS: By the
      manual palpation test, the fusion rates were 37.5%, 93.8%, and 100%, for groups 1
      3, respectively (P < 0.05). By radiography, the control group fusion rate was
      68.7% compared with 100% for the experimental groups (P < 0.05). The mean bone
      volumes of the fusion mass were 2142.2 +/- 318.5, 3132.9 +/- 632.1, and 4181.6 +/
      609.5 mm3 for groups 1-3, respectively (P < 0.05). CONCLUSIONS: The
      demineralized bone matrix-gel strip was able to function as both a bone-graft
      enhancer and a bone graft substitute in rabbit posterolateral spine fusion.

PMID- 17202891
TI  - Titanium versus stainless steel for anterior spinal fusions: an analysis of rod
      stress as a predictor of rod breakage during physiologic loading in a bovine
      model.
AB  - STUDY DESIGN: In vitro biomechanical evaluation of rod stress during physiologic
      loading of anterior scoliosis instrumentation. OBJECTIVES: To determine effects
      of material properties and rod diameter on rod stresses in anterior scoliosis
      instrumentation. SUMMARY OF BACKGROUND DATA: Relationships between
      instrumentation dimensions, materials, and potential rod failure in anterior
      scoliosis instrumentation remain unclear. METHODS: Eighteen immature bovine
      spines were randomized to 3 groups: 1) 4.0-mm stainless steel, 2) 5.0-mm
      stainless steel, and 3) 4.75-mm titanium alloy. Spines underwent physiologic
      tests in flexion-extension, lateral bending, and torsion. Rod surface strains
      were converted to rod stress and normalized to each material's yield stress.
      Construct stiffness and the normalized rod stresses were compared with a one-way
      ANOVA (P < 0.05). RESULTS: The 4.0-mm steel and 4.75-mm titanium construct
      stiffness was similar across all tests. The 5.0-mm steel system was significantly
      stiffer than 4.0-mm steel (lateral bending/torsion) and 4.75-mm titanium
      (torsion/flexion) constructs. Rod surface stress was significantly lower for the
      4.75-mm titanium rod compared with 4.0-mm and 5.0-mm steel rods for all tests.
      CONCLUSIONS: The percentage of yield stress was lowest for the 4.75-mm Ti rod for
      all tests due to titanium's greater yield stress. This suggests the 4.75-mm rod
      has a lower fatigue failure risk than either steel construct.

PMID- 17202892
TI  - Is it safer to place pedicle screws in the lower thoracic spine than in the upper
      lumbar spine?
AB  - STUDY DESIGN: An anatomic study of 100 patients comparing the pedicle isthmic
      width of the lower thoracic spine and the upper lumbar spine using magnetic
      resonance imaging. OBJECTIVES: To compare the lower thoracic pedicles and upper
      lumbar pedicles in nondeformity patients as a surrogate measure of safety of
      pedicle screw use. SUMMARY OF BACKGROUND DATA: Pedicle isthmic width is the
      significant limiting factor in the safety and proper placement of transpedicular
      screws. The presumption in the past has been that the lumbar pedicles are larger
      than the thoracic pedicles. Few publications in the English-language literature
      specifically evaluate the association between the pedicle isthmic widths of the
      lower thoracic and upper lumbar. METHODS: The study evaluates 100 patients,
      without coronal spinal deformities. MRIs were obtained of the pedicles from T10
      to L2 and subsequently measured using the axial T2-weighted views. Lower thoracic
      and upper lumbar pedicle isthmus, the narrowest section of pedicle, was
      investigated and compared. The "medial pedicle to medial rib corridor" at T10-T12
      was defined and measured as part of the methodology of the study. Statistical
      analysis included one-way analysis of variance with post hoc least significant
      difference pairwise comparisons. RESULTS: The smallest pedicle isthmic width was
      at L1 (mean +/- SD, 6.0 +/- 1.6 mm), while T12 (mean +/- SD, 7.6 +/- 1.5 mm) had
      the largest pedicle width. Although smaller in diameter than T12, both T10 (mean
      +/- SD, 6.2 +/- 1.2 mm) and T11 (mean +/- SD, 7.5 +/- 1.6 mm) had larger pedicle
      width than L1 (P < 0.01). Pedicle widths were larger in males compared with
      females (P < 0.05). CONCLUSIONS: The results show that the lower thoracic
      pedicles are larger than the upper lumbar pedicles. This may make it safer to
      place screws in the lower thoracic spine than in the upper lumbar spine. Upper
      lumbar may be so small (<5 mm) to preclude safe conventional screw placement.

PMID- 17202893
TI  - Biomechanical evaluation of the Total Facet Arthroplasty System: 3-dimensional
      kinematics.
AB  - STUDY DESIGN: An in vitro biomechanical study to quantify 3-dimensional
      kinematics of the lumbar spine following facet arthroplasty. OBJECTIVES: To
      compare the multidirectional flexibility properties and helical axis of motion of
      the Total Facet Arthroplasty System (TFAS) (Archus Orthopedics, Redmond, WA) to
      the intact condition and to posterior pedicle screw fixation. SUMMARY OF
      BACKGROUND DATA: Facet arthroplasty in the lumbar spine is a new concept in the
      field of spinal surgery. The kinematic behavior of any complete facet
      arthroplasty device in the lumbar spine has not been reported previously.
      METHODS: Flexibility tests were conducted on 13 cadaveric specimens in an intact
      and injury model, and after stabilization with the TFAS and posterior pedicle
      screw fixation at the L4-L5 level. A pure moment of +/-10 Nm with a compressive
      follower preload of 600 N was applied to the specimen in flexion-extension, axial
      rotation, and lateral bending. Range of motion (ROM), neutral zone, and helical
      axis of motion were calculated for the L4-L5 segment. RESULTS: ROM with the TFAS
      was 81% of intact in flexion (P = 0.035), 68% in extension (P = 0.079), 88% in
      lateral bending (P = 0.042), and 128% in axial rotation (P = 0.013). The only
      significant change in neutral zone with TFAS compared to the intact was an
      increase in axial rotation (P = 0.011). The only significant difference in
      helical axis of motion location or orientation between the TFAS and intact
      condition was an anterior shift of the helical axis of motion in axial rotation
      (P = 0.013). CONCLUSIONS: The TFAS allowed considerable motion in all directions
      tested, with ROM being less than the intact in flexion and lateral bending, and
      greater than the intact in axial rotation. The helical axis of motion with the
      TFAS was not different from intact in flexion-extension and lateral bending, but
      it was shifted anteriorly in axial rotation. The kinematics of the TFAS were more
      similar to the intact spine than were the kinematics of the posterior fixation
      when applied to a destabilized lumbar spine.

PMID- 17202894
TI  - Comparison of multisegment anterior cervical fixation using bone strut graft
      versus a titanium rod and buttress prosthesis: analysis of outcome with long-term
      follow-up and interview by independent physician.
AB  - STUDY DESIGN: A retrospective study of 73 consecutive patients who underwent
      cervical corpectomy and anterior strut fixation over 3 or more disc levels
      between July 1989 and May 1999. OBJECTIVE: To compare the efficacy of cervical
      spine fixation by autologous strut graft from iliac crest or fibula versus a
      titanium prosthesis without bone graft. SUMMARY OF BACKGROUND DATA: Strut
      grafting after multilevel anterior cervical corpectomy remains a challenging
      procedure, with published dislocation rates from 0% to 71%, and nonunion from 0%
      to 54%. This paper describes a quicker and easier alternative to the use of a
      bone strut, imparting a very high degree of immediate spinal stability, and
      osseous integration equivalent to bone fusion. METHODS: Thirty-eight bone-graft
      operations and 38 titanium prosthesis operations were performed on 73 patients
      between July 24, 1989 and May 20, 1999. Average follow-up was 53.2 months (range
      19.8-134). RESULTS: The group of patients who received the prosthesis was
      significantly older than the bone-grafted group and required significantly more
      segments excised, but operation times were significantly shorter than for the
      bone strut operation. The titanium prosthesis had a lower incidence of
      dislodgement in the early postoperative period (1/38 vs. 4/38 for bone struts)
      but a higher rate of late reoperation (4/38 vs. 1/38 for bone struts). The SF-36
      scores in the domain of Physical Function (only) were significantly higher in the
      bone-grafted group (P = 0.016, Mann Whitney), consistent with the difference in
      mean ages of the 2 groups. The groups were indistinguishable by Odom criteria,
      patient verdict, pain scores, analgesic intake, length of hospital stay,
      radiologic fusion rate, and residual symptoms. CONCLUSION: A titanium rod and
      buttress prosthesis may be a faster and easier alternative to conventional iliac
      crest/fibula autograft after multisegmental cervical vertebral corpectomy.

PMID- 17202895
TI  - Assessment of forearm pronation strength in C6 and C7 radiculopathies.
AB  - STUDY DESIGN: Consecutive case series of patients with C6 and C7 radiculopathies.
      OBJECTIVES: To explore the clinical utility and reliability of manual muscle
      testing of forearm pronation strength in C6 and C7 radiculopathies. SUMMARY OF
      BACKGROUND DATA: EMG evidence of denervation of the pronator teres was the most
      common finding in C6 radiculopathies, and frequently present in C7
      radiculopathies. Clinical evaluation of the pronator teres through manual muscle
      testing of forearm pronation has never been explored; therefore, its clinical
      utility is unknown as compared with the muscle groups that are traditionally
      evaluated. METHODS: Fifty-five subjects with diagnostic imaging evidence of
      either C6 (n = 25) or C7 (n = 30) cervical root compression and clinical symptoms
      consistent with cervical radiculopathy were recruited for this study. These
      subjects underwent manual muscle testing of forearm pronation, wrist extension,
      elbow flexion, and elbow extension. The frequency of impaired strength was
      recorded and compared for C6 and C7 radiculopathies. A second examiner evaluated
      each subject, with his or her findings compared with the first examiner only for
      the determination of interrater reliability. RESULTS: In C6 radiculopathy
      subjects, forearm pronation weakness was present in 72%, was twice as common as
      wrist extension weakness, was present in all cases where elbow flexion or wrist
      extension weakness was noted, and was found in all but 2 subjects where elbow
      extension weakness was present. In C7 radiculopathy subjects, forearm pronation
      weakness accompanies elbow extension weakness in 23% of subjects and was the only
      weakness in 10% of subjects. Manual muscle testing demonstrated adequate
      interrater reliability. CONCLUSIONS: Forearm pronation weakness is the most
      frequent motor finding in C6 radiculopathies and may be noted is some cases of C7
      nerve root compression.

PMID- 17202896
TI  - Active lifestyle protects against incident low back pain in seniors: a population
      based 2-year prospective study of 1387 Danish twins aged 70-100 years.
AB  - STUDY DESIGN: Prospective cohort study of twins. OBJECTIVES: To investigate
      associations between physical activity, physical function, and incident low back
      pain (LBP) in an elderly population. SUMMARY OF BACKGROUND DATA: The relationship
      between an active lifestyle and LBP in seniors is unknown. METHODS: Participants
      in the population-based Longitudinal Study of Aging Danish Twins free from LBP at
      baseline (no LBP during the past month) were included, and interview data on
      physical activity, overall physical function, and LBP at baseline and follow-up
      were obtained. Associations between levels of physical activity and LBP were
      estimated using logistic regression for the entire cohort, and using a matched
      case-control design for twin pairs discordant for physical activity. Absolute
      risk and relative risks for incident LBP in relation to physical activity were
      calculated for participants with higher or lower than average physical function
      at baseline. Absolute risk for LBP was also calculated for participants based on
      whether they remained active or inactive between baseline and follow-up or
      changed activity level. RESULTS: A total of 1387 persons aged 70-100 at baseline
      were included in the analyses, including 86 twin pairs discordant for physical
      activity at baseline. In the total sample, 83% were engaged in light physical
      activity, and 42% of men and 35% of women were engaged in strenuous physical
      activity at least weekly. Being engaged in strenuous physical activity at
      baseline was strongly protective in relation to both having had any LBP (odds
      ratio 0.21, 95% confidence interval 0.12-0.37 for intra-pair analysis) and having
      had LBP lasting more than 30 days altogether during the past year at follow-up
      (odds ratio 0.08, 95% confidence interval 0.03-0.18 for intra-pair analysis).
      Statistically significant dose-response associations between increasing frequency
      of strenuous physical activity and magnitude of this protective effect were
      found. Participants with poor initial physical function experienced the strongest
      protective effect of strenuous physical activity. Finally, LBP does not appear to
      be an important factor affecting whether participants remained engaged in
      strenuous physical activity at baseline and follow-up or vice versa. CONCLUSIONS:
      Strenuous physical activity at least once a week is protective for incident LBP
      in seniors.

PMID- 17202897
TI  - Herbal medicine for low back pain: a Cochrane review.
AB  - STUDY DESIGN: A systematic review of randomized controlled trials. OBJECTIVES: To
      determine the effectiveness of herbal medicine compared with placebo, no
      intervention, or "standard/accepted/conventional treatments" for nonspecific low
      back pain. SUMMARY OF BACKGROUND DATA: Low back pain is a common condition and a
      substantial economic burden in industrialized societies. A large proportion of
      patients with chronic low back pain use complementary and alternative medicine
      (CAM) and/or visit CAM practitioners. Several herbal medicines have been
      purported for use in low back pain. METHODS: The following databases were
      searched: Medline (1966 to April 2003), Embase (1980 to April 2003), Cochrane
      Controlled Trials Register (Issue 1, 2003), and Cochrane Complementary Medicine
      (CM) field Trials Register. Additionally, reference lists in review articles,
      guidelines, and in the retrieved trials were checked. Randomized controlled
      trials (RCTs), using adults (>18 years of age) suffering from acute, subacute, or
      chronic nonspecific low back pain. Types of interventions included herbal
      medicines defined as a plant that is used for medicinal purposes in any form.
      Primary outcome measures were pain and function. Two reviewers (J.J.G. and
      M.W.T.) conducted electronic searches in all databases. One reviewer (J.J.G.)
      contacted content experts and acquired relevant citations. Authors, title,
      subject headings, publication type, and abstract of the isolated studies were
      downloaded or a hard copy was retrieved. Methodologic quality and clinical
      relevance were assessed separately by two individuals (J.J.G. and M.W.T.).
      Disagreements were resolved by consensus. RESULTS: Ten trials were included in
      this review. Two high-quality trials utilizing Harpagophytum procumbens (Devil's
      claw) found strong evidence for short-term improvements in pain and rescue
      medication for daily doses standardized to 50 mg or 100 mg harpagoside with
      another high-quality trial demonstrating relative equivalence to 12.5 mg per day
      of rofecoxib. Two moderate-quality trials utilizing Salix alba (White willow
      bark) found moderate evidence for short-term improvements in pain and rescue
      medication for daily doses standardized to 120 mg or 240 mg salicin with an
      additional trial demonstrating relative equivalence to 12.5 mg per day of
      rofecoxib. Three low-quality trials using Capsicum frutescens (Cayenne) using
      various topical preparations found moderate evidence for favorable results
      against placebo and one trial found equivalence to a homeopathic ointment.
      CONCLUSIONS: Harpagophytum procumbens, Salix alba, and Capsicum frutescens seem
      to reduce pain more than placebo. Additional trials testing these herbal
      medicines against standard treatments will clarify their equivalence in terms of
      efficacy. The quality of reporting in these trials was generally poor; thus,
      trialists should refer to the CONSORT statement in reporting clinical trials of
      herbal medicines.

PMID- 17202898
TI  - The selection of operative versus nonoperative treatment in patients with adult
      scoliosis.
AB  - STUDY DESIGN: Retrospective case-control matched series. OBJECTIVE: The purpose
      of this study is to define factors that influence the patient and surgeon in the
      selection of surgical versus nonsurgical treatment for adult scoliosis. SUMMARY
      OF BACKGROUND DATA: There is no literature that specifically examines why adult
      scoliosis patients and/or their surgeons choose surgical versus nonsurgical
      treatment. METHODS: This study analyzes a prospective multicentered database for
      adult spinal deformity. A logistic regression technique was used to perform case
      control matching. A total of 161 matched pairs were compared for radiographic
      characteristics, questionnaire responses, and standardized outcome measures.
      RESULTS: Nonsurgical patients had greater preoperative medical risk factors.
      Surgical patients had larger thoracic (51 degrees vs. 44 degrees, P = 0.006) and
      thoracolumbar/lumbar curves (55 degrees vs. 43 degrees, P = 0.000). Surgical
      patients had more frequent leg pain (47% vs. 35%, P = 0.04). They reported a
      higher mean level of daily back pain (P = 0.008) and more frequent moderate-to
      severe back pain over the past 6 months (P = 0.03). There were also significant
      differences in perception of appearance and social function between the cohorts.
      CONCLUSIONS: This study emphasizes the complexity of surgical decision making for
      adult scoliosis patients. It also underscores the importance of patient-based
      health status measures in evaluating the adult scoliosis patient.

PMID- 17202899
TI  - Comparison of Cobb angle measurement of scoliosis radiographs with preselected
      end vertebrae: traditional versus digital acquisition.
AB  - STUDY DESIGN: Prospective study. OBJECTIVE: To compare variability in Cobb angle
      between digitally and traditionally acquired scoliosis radiographs. SUMMARY OF
      BACKGROUND DATA: Previous studies have shown that the 95% confidence interval for
      Cobb angle can vary from 2.6 degrees to 8.8 degrees. No study directly comparing
      Cobb angles measured from traditional and digitally acquired radiographs has been
      reported. METHODS: A spine model simulating 25 single right thoracic curves
      (range, 20 degrees-60 degrees) was imaged using traditional and digital
      techniques. Traditional films and miniaturized printed digital films were each
      measured twice manually. Digital films were also measured twice using computer
      imaging software. RESULTS: Overall mean angle and (95% confidence interval) were
      41.7 degrees (39.1 degrees-44.3 degrees) for traditional, 40.6 degrees (37.4
      degrees-43.8 degrees) for digital, and 39.7 degrees (36.3 degrees-43.1 degrees)
      for computer measurements. Overall correlation was 0.994 for traditional and
      digital, 0.987 for traditional and computer, and 0.993 for digital and computer.
      Fixed effect model analysis demonstrated that, although a statistically
      significant difference existed between the 3 methods of measuring the Cobb angle
      (P < 0.0001), the difference between methods was less than 2 degrees.
      CONCLUSIONS: Any of the 3 evaluated methods of measurement can be used to measure
      Cobb angles. Additionally, the methods can be used interchangeably.

PMID- 17202900
TI  - Factors of thoracic cage deformity that affect pulmonary function in adolescent
      idiopathic thoracic scoliosis.
AB  - STUDY DESIGN: This clinical study examined the association between pulmonary
      function and thoracic cage deformities in scoliosis. OBJECTIVE: To determine the
      factors in spinal and thoracic cage deformities that affect pulmonary function in
      scoliosis. SUMMARY OF BACKGROUND DATA: Pulmonary function in scoliosis has
      generally been evaluated in terms of lateral spinal curvature. No previous report
      has evaluated changes in pulmonary function taking into consideration
      measurements reflecting not only spinal curvature but also thoracic cage
      deformities, although scoliosis is a three-dimensional deformity. METHODS: A
      total of 109 patients (mean age, 14.2 years) with adolescent idiopathic right
      thoracic scoliosis (mean lateral spinal curvature, 37.7 degrees) had full
      assessment of pulmonary function and a radiographic evaluation from radiographs
      of the whole spine, Moire topography, and thoracic computed tomography. RESULTS:
      Multiple regression analysis (stepwise method) was performed at each vertebral
      level from T3-T12 to identify the factor that most strongly affects %VC. The
      correlation coefficient was highest at T9 and next highest at T8, with values of
      0.641 (r2 = 0.411, P < 0.0001) and 0.625 (r2 = 0.390, P < 0.0001), respectively.
      At T9, multiple regression analysis showed that the sagittal diameter of the
      thoracic cage and the total lung area were identified as factors that most
      strongly affect %VC. Similarly, the sagittal diameter of the thoracic cage and
      the rotation angle to the sagittal plane were identified at T8. CONCLUSIONS: The
      factors that reduced %VC were the sagittal diameter of the thoracic cage, total
      lung area and vertebral rotation at the T8 and T9 levels.

PMID- 17202901
TI  - The use of computed tomography angiography to define the prevertebral vascular
      anatomy prior to anterior lumbar procedures.
AB  - STUDY DESIGN: Prospective cohort. OBJECTIVE: To determine the efficacy of a
      single-slice computed tomography (CT) angiogram to define the prevertebral
      anatomy in patients undergoing an anterior lumbar spine procedure. SUMMARY OF
      BACKGROUND DATA: Preoperative planning with precise prevertebral anatomic details
      can help in mini-open anterior lumbar approaches. METHODS: A total of 76
      consecutive patients undergoing a minimal incision approach for anterior lumbar
      surgery were evaluated before surgery with CT angiography. The prevertebral
      anatomy was documented, and the patients were observed during treatment. RESULTS:
      There were no complications related to CT angiography. This study directly
      influenced surgical decision making and the treatment options in 21% of patients.
      The vena caval confluence limited access to the L5-S1 disc in 3% of patients and
      at the L4-L5 disc in 92% of the patients. Prevertebral anatomic anomalies were
      found in 11.8% of patients. Atherosclerotic disease was discovered in 17% of the
      patients. The major complication rate was 7.5%. CT angiography correlated with
      intraoperative vascular anatomy in all cases. CONCLUSION: Preoperative CT
      angiography before anterior approaches was determined to be effective in
      evaluating the prevertebral vascular anatomy.

PMID- 17202902
TI  - Degenerative lumbar spondylolisthesis: an epidemiological perspective: the
      Copenhagen Osteoarthritis Study.
AB  - STUDY DESIGN: A cross-sectional epidemiological survey of 4151 participants of
      the Copenhagen Osteoarthritis Study. OBJECTIVE: To identify prevalences and
      individual risk factors for degenerative lumbar spondylolisthesis. SUMMARY OF
      BACKGROUND DATA: The Copenhagen Osteoarthritis Study has registered health
      parameters since 1976. In 1993, standardized, lateral radiographs of the lumbar
      spine were recorded. There were 1533 men and 2618 women. METHODS: Statistical
      correlations were made between degenerative spondylolisthesis, and physical,
      occupational, and general epidemiological data. RESULTS: A total of 254 cases of
      lumbar slip were found (males 2.7%, females 8.4%). In females, no significant
      relationship between age at menopause or childbirths and the presence of
      degenerative spondylolisthesis were found. In women, relationships between body
      mass index (BMI) in 1976 and L4 olisthesis (P = 0.001), and between BMI in 1993
      and both L4 and L5 olisthesis were found (L4: P = 0.003; L5: P = 0.006). Lumbar
      lordosis was associated with degenerative spondylolisthesis in women.
      Occupational exposures to daily lifting or smoking were not associated with
      degenerative spondylolisthesis. Degenerative spondylolisthesis was associated
      with increased age in both sexes (L4: P < 0.001; L5: P < 0.001). CONCLUSIONS: BMI
      longitudinally and at index evaluations, age, and angle of lordosis were
      significantly associated with degenerative spondylolisthesis in women. In men, no
      individual risk factors for degenerative spondylolisthesis were found, save
      increased age.

PMID- 17202903
TI  - Does multidisciplinary rehabilitation benefit whiplash recovery?: results of a
      population-based incidence cohort study.
AB  - STUDY DESIGN: Population-based, incidence cohort. OBJECTIVES: To evaluate a
      government policy of funding community and hospital-based fitness training and
      multidisciplinary rehabilitation for whiplash. SUMMARY OF BACKGROUND DATA:
      Although insurance benefits commonly include rehabilitation for whiplash, its
      effectiveness is unknown. METHODS: All Saskatchewan adults treated for whiplash
      (n = 6,021) over a 2-year period were followed up at 6 weeks, 3, 6, 9, and 12
      months. Recovery was defined by self-report of improvement. Recovery times were
      compared between those attending fitness training at health clubs (n = 833),
      multidisciplinary outpatient rehabilitation (n = 468), and multidisciplinary
      inpatient rehabilitation (n = 135) to those receiving usual insured individual
      care. RESULTS: Recovery was 32% slower in those receiving fitness training within
      69 days of injury (P = 0.001) and 19% slower when received within 119 days of
      injury (P = 0.041). Recovery was 50% slower in those receiving outpatient
      rehabilitation within 119 days of injury (P = 0.001). Attending inpatient
      rehabilitation did not influence recovery rates during the follow up (P = 0.131).
      Multivariable adjustment for important prognostic factors did not change these
      results. CONCLUSIONS: We found no evidence to support the effectiveness of a
      population-based program of fitness training and multidisciplinary rehabilitation
      for whiplash. Rehabilitation programs should be tested in randomized trials
      before being recommended to injured populations.

PMID- 17202904
TI  - Volume and characteristics of inpatient and ambulatory medical care for neck pain
      in the United States: data from three national surveys.
AB  - STUDY DESIGN: Secondary analysis of national survey data. OBJECTIVE: To describe
      the volume and characteristics of outpatient visits to physician offices,
      hospital outpatient departments and emergency departments, and inpatient hospital
      utilization for neck pain in the United States. We also examined the use of
      pathology-based versus symptom-based diagnoses on a national scale. SUMMARY OF
      BACKGROUND DATA: Descriptions of the epidemiology of neck pain will assist policy
      makers and clinicians in understanding the impact of neck pain on society.
      METHODS: Analysis of combined survey data from the 2001 and 2002 National
      Ambulatory Medical Care Survey, National Hospital Ambulatory Medical Care Survey,
      and National Hospital Discharge Survey, from the Centers for Disease Control and
      Prevention/National Center for Health Statistics. RESULTS: During 2001 and 2002,
      an average of 10.2 million visits were made annually. At 64% of visits, a symptom
      based diagnosis was used. An annual average of 179,000 hospital discharges for
      neck pain was recorded and 94% received a pathology-based diagnosis. Most (79%)
      had surgery for the neck problem. CONCLUSIONS: Outpatient visits for neck pain
      are common in the United States, and the majority are given symptom-based rather
      than pathology-based diagnoses. An alternative diagnostic taxonomy may be needed
      to guide treatment, particularly for patients with vague, symptom-based
      diagnoses. Hospitalizations for neck pain often include surgical procedures, but
      21% received no surgery.

PMID- 17202907
TI  - Innate handedness and disease-specific mortality in women.
AB  - BACKGROUND: Left-handedness has been reported to be associated with reduced life
      expectancy, but the evidence is far from conclusive. METHODS: We studied the
      association between innate handedness and total mortality, as well as cause
      specific mortality, in a cohort of 12,178 middle-aged Dutch women who were
      followed for almost 13 years. The relation between handedness and mortality was
      analyzed using Cox regression in a case-cohort approach, in which a random sample
      of 1500 women was used to represent person-years under observation for the entire
      cohort. RESULTS: During a median follow-up of 12.6 years, 252 women died. Hazard
      ratios comparing left-handed women with other women were 1.4 for all-cause
      mortality (95% confidence interval = 0.9-2.0), 1.7 for total cancer mortality
      (1.0-2.7), 2.0 for breast cancer mortality (0.8-4.6), 4.6 for colorectal cancer
      mortality (1.5-14.3), 1.3 mortality from diseases of the circulatory system (0.5
      3.3), and 3.7 for cerebrovascular mortality (1.1-12.1), after adjusting for
      potential confounders (socioeconomic status, age, body mass index, and cigarette
      smoking status at study recruitment). CONCLUSIONS: Left-handedness is associated
      with higher mortality in women.

PMID- 17202906
TI  - Margin-free spondylectomy for extended malignant spine tumors: surgical technique
      and outcome of 13 cases.
AB  - STUDY DESIGN: Description of surgical technique and retrospective review of 13
      cases. OBJECTIVES: To describe the surgical technique of margin-free
      spondylectomy and the outcome of 13 cases and to discuss the advantages and
      limitations of the procedure. SUMMARY OF BACKGROUND DATA: Recently, spondylectomy
      became a standard procedure by several pioneers. For extended malignant spine
      tumors involving pedicles or epidural space, however, performing an "en bloc"
      resection with a tumor-free margin remains a challenge. METHODS: Our procedure
      consists of a combined anterior and posterior procedure with one or two stages.
      In the anterior procedure, tumor vertebrae are covered by the pleura or psoas
      muscles as a barrier. The posterior procedure includes decompression through the
      intact posterior elements, coverage of the tumor with all possible soft tissue
      barriers, and en bloc extirpation by rotating the tumor vertebrae around the
      spinal cord. We performed this procedure in 13 cases: 3 chondrosarcoma, 3 giant
      cell tumor, 1 osteosarcoma, 1 chordoma, and 5 metastases. RESULTS: Neurologic
      status and pain improved in all cases except asymptomatic cases. There was no
      local recurrence, except in 2 cases (chondrosarcoma with extirpation of 5
      vertebrae, chordoma with multiple previous surgeries). Two cases of
      chondrosarcoma were disease-free 14 years and 13 years after surgery,
      respectively. CONCLUSION: Although the best chance for a cure in extended
      malignant tumors of the spine is realized through wide resection, the procedure
      is not yet standardized. Margin-free spondylectomy is technically demanding, but
      the procedure can be used with a confidence as a more radical surgery for tumors
      extending to the epidural space and the unilateral pedicle. A key to success is
      the surgical technique, including a 360 degree dissection around the tumor
      vertebrae, instrumentation, and removal of the lesion with all possible soft
      tissues maintained intact to function as a barrier, like the dura mater.

PMID- 17202908
TI  - Nasopharyngeal carriage of respiratory pathogens in children undergoing pressure
      equalization tube placement in the era of pneumococcal protein conjugate vaccine
      use.
AB  - OBJECTIVE: To define carriage of bacterial respiratory pathogens in children
      undergoing pressure equalization tube placement. STUDY DESIGN: Nasopharyngeal
      cultures were performed during tube placement. Antibiotic susceptibilities and
      serotypes of pneumococci were determined. RESULTS: Sixty-nine Streptococcus
      pneumoniae, 72 Haemophilus influenzae (41% beta-lactamase positive), and 39
      Moraxella catarrhalis (all beta-lactamase positive) were isolated from 201
      children. Overall, 42% of pneumococci were nonsusceptible to penicillin, and
      34.8% were resistant to macrolides. In relation to the pneumococcal conjugate
      vaccine, 17.4% were vaccine, 31.9% vaccine-related, and 50.7% nonvaccine
      serotypes. CONCLUSION: Twenty-five percent of children colonized with pneumococci
      carried antibiotic resistant nonvaccine serotypes rarely detected before the
      introduction of pneumococcal conjugate vaccine, including serotype 19A isolates
      (7%) resistant to all oral agents tested and type 35B isolates (12%)
      nonsusceptible to penicillin and cefuroxime. SIGNIFICANCE: Pneumococcal
      colonization suggests replacement of vaccine serotypes with vaccine related and
      nonvaccine serotypes, many of which are resistant to common oral antimicrobials.

PMID- 17202912
TI  - Rotatory instability of the knee: its pathogenesis and a clinical test to
      demonstrate its presence. 1968.

PMID- 17202909
TI  - Auricle reconstruction with a nickel-titanium shape memory alloy as the
      framework.
AB  - OBJECTIVE: The objective of this study is to explore the biocompatibility and
      implantability of a nickel-titanium (NiTi) alloy in auricle reconstruction.
      METHODS AND MATERIALS: Twelve New Zealand rabbits underwent subcutaneous
      implantation with a NiTi alloy framework shaped like the human auricle under
      general anesthesia. The implant was inserted after skin expansion. Implant
      vascularization was evaluated at months 1, 3, 6, 9, and 12 after implantation by
      histologic analysis. Immunohistochemical methods were used to examine expression
      of vascular endothelial growth factor in tissue around the implant. The
      fibrovascular ingrowth rate of implants was determined by bone scanning using
      (99m)Tc-PYP. The surface of the NiTi alloy implant was examined microscopically
      with scanning electron microscopy. RESULT: The implant harvested showed only
      partial vascularization at 1 month and completely vascularized at 3 months. The
      amount of vascular endothelial growth factor-positive cells was markedly
      increased at 6 months and reached the highest number at 3 months. The
      fibrovascular ingrowth rate of implant was assessed by (99m)Tc-PYP bone scan
      using ratios of (99m)Tc-PYP activity in placement regions versus the
      contralateral normal region. One rabbit had exposure of the NiTi alloy framework
      as a result of overlying skin flap necrosis. It was rescued with animal skin
      without the complete removal of the framework. All the other rabbits tolerated
      the implant well, and there were no complications. CONCLUSION: The NiTi alloy
      implant represents an alternative implant for auricular reconstruction.

PMID- 17202914
TI  - Artificial ligaments at the knee: a technique. 1934.

PMID- 17202915
TI  - On the injuries to the ligaments of the knee joint: a clinical study. 1938.

PMID- 17202916
TI  - Surgical treatment of fresh injuries to the major ligaments of the knee. 1950.

PMID- 17202917
TI  - Intraarticular rupture pattern of the ACL.
AB  - To date, the intraarticular rupture pattern of the anterior cruciate ligament
      (ACL) has not been reported. The ACL is a complex structure consisting of two
      functionally synergistic structures: the anteromedial (AM) and posterolateral
      (PL) bundle. The purpose of our study was to evaluate the intraarticular rupture
      pattern of the ACL with regard to its two functional bundles. We examined ACL
      rupture patterns with regard to the integrity of AM and PL bundle in 121
      consecutive patients undergoing anterior cruciate ligament reconstruction surgery
      within 120 days after injury. The intraarticular pattern was observed by one
      experienced surgeon. In 25% of the patients a partial rupture of the ACL was
      found, whereas in the remaining 75% a complete rupture of AM and PL bundles was
      seen. A partial rupture could only be detected by careful dissection of the
      ligament. In 44% of all patients the AM and PL bundles did not rupture at the
      same location. In 12% of the patients the PL bundle showed no signs of rupture.
      When performing ACL reconstruction, care should be taken when dissecting down the
      ACL remnants to evaluate intact fiber bundles of the ACL.

PMID- 17202918
TI  - In vivo knee kinematics during gait reveals new rotation profiles and smaller
      translations.
AB  - In order to identify abnormal or pathological motions associated with clinically
      relevant questions such as injury mechanisms or factors leading to joint
      degeneration, it is essential to determine the range of normal tibiofemoral
      motion of the healthy knee. In this study we measured in vivo 3D tibiofemoral
      motion of the knee during gait and characterized the nonsagittal plane rotations
      and translations in a group of six healthy young adults. The subjects were
      instrumented with markers placed on intracortical pins inserted into the tibia
      and femur as well as marker clusters placed on the skin of the thigh and shank.
      The secondary rotations and translation excursions of the knee were much smaller
      than those derived from skin markers and previously described in the literature.
      Also, for a given knee flexion angle, multiple combinations of transverse and
      frontal plane knee translation or rotation positions were found. This represents
      normal knee joint motions and ensemble averaging of gait data may mask this
      important subject-specific information.

PMID- 17202919
TI  - Single-and double-incision double-bundle ACL reconstruction.
AB  - Double-bundle anterior cruciate ligament (ACL) reconstruction is intended to
      replicate the anatomy and the function of the anteromedial and posterolateral
      bundles of the native ACL to improve patients' satisfaction and knee stability.
      We prospectively assigned 75 consecutive patients with an isolated ACL lesion to
      one of three sequential groups of 25 patients each. Group I received a single
      bundle, single-incision transtibial ACL reconstruction. Groups II and III
      received a double-bundle reconstruction with a single-incision transtibial
      technique or a double-bundle, twoincision outside-in technique, respectively. We
      obtained subjective International Knee Documentation Committee and Knee Injury
      and Osteoarthritis Outcome Score evaluations and objective International Knee
      Documentation Committee scores and KT-1000 measurements preoperatively and at
      followup. All patients reached a minimum followup of 2 years. KT side-to-side
      difference in Groups I, II, and III were 2.4, 1.6 and 1.4 mm, respectively. Group
      III had fewer patients with a positive pivot shift than Group I. The double
      bundle double-incision outside-in ACL reconstruction resulted in improved
      anteroposterior stability and less residual pivot shift than single-incision
      single-bundle technique.

PMID- 17202922
TI  - Standards for ethical publication.

PMID- 17202924
TI  - Changes in treatment of advanced oropharyngeal cancer, 1985-2001.
AB  - OBJECTIVE: The aim of this study is to describe patterns of care of advanced
      oropharyngeal cancer during 1985 to 2001. METHODS: We extracted oropharyngeal
      squamous cell cancer cases from the National Cancer Database. Type of initial
      treatment, type of facility, stage of tumor, payer status, and demographic
      variables were collected. Fisher exact test was used to compare the patient
      demographic and clinical characteristics across facility types. Weighted least
      squares regression analysis was used to analyze treatment trends over time and t
      tests were done to test for significance in trends. RESULTS: A total of 54,801
      cases were available for analysis. Teaching/research facilities treated a
      disproportionately higher number of advanced-stage cancers (81%, P < .01). In
      addition, these facilities treat a higher percentage of uninsured (7%, P < .01)
      and nonwhite patients (27%, P < .01). The use of organ preservation protocols
      (chemoradiation) increased from 15% in 1985 to 29% in 2001 (beta1 = 0.0080, P <
      .05), whereas the use of radiation alone decreased from 42% in 1985 to 27% in
      2001 (beta1 = -0.0118, P < .05). The use of cancer-directed surgery remained
      stable. There was no difference in rates of chemoradiation for advanced
      oropharyngeal cancer across facility types. CONCLUSIONS: Our results suggest that
      chemoradiation is increasingly becoming more prevalent at all facility types. The
      use of radiation alone as primary treatment significantly declined during the
      study period. In view of the complexity and multidisciplinary nature of treatment
      for oropharyngeal cancer, it is recommended that care of such patients be
      discussed at institutional tumor boards and that the recommendations be
      systematically recorded and documented in hospital cancer registries.

PMID- 17202923
TI  - Intratympanic dexamethasone for sudden sensorineural hearing loss after failure
      of systemic therapy.
AB  - OBJECTIVE: Intratympanic steroids are increasingly used in the treatment of inner
      ear disorders, especially in patients with sudden sensorineural hearing loss
      (SNHL) who have failed systemic therapy. We reviewed our experience with
      intratympanic steroids in the treatment of patients with sudden SNHL to determine
      overall success, morbidity, and prognostic factors. HYPOTHESIS: Intratympanic
      steroids have minimal morbidity and the potential to have a positive effect on
      hearing recovery in patients with sudden SNHL who have failed systemic therapy.
      STUDY DESIGN: The authors conducted a retrospective review. METHODS: Patients
      presenting with sudden SNHL defined as a rapid decline in hearing over 3 days or
      less affecting 3 or more frequencies by 30 dB or greater who underwent
      intratympanic steroids therapy (24 mg/mL dexamethasone) were reviewed. Excluded
      were patients with Meniere disease, retrocochlear disease, autoimmune HL, trauma,
      fluctuating HL, radiation-induced HL, noise-induced HL, or any other identifiable
      etiology for sudden HL. Patients who showed signs of fluctuation of hearing after
      injection were excluded. Pretreatment and posttreatment audiometric evaluations
      including pure-tone average (PTA) and speech reception threshold (SRT) were
      analyzed. Patient variables as they related to recovery were studied and included
      patient age, time to onset of therapy, status of the contralateral ear, presence
      of diabetes, severity of HL, and presence of associated symptoms (tinnitus,
      vertigo). A 20-dB gain in PTA or a 20% improvement in SDS was considered
      significant. RESULTS: : Forty patients fit the criteria for inclusion in the
      study. The mean age of the patients was 54.8 years with a range from 17 to 84
      years of age. Overall, 40% (n = 16) showed any improvement in PTA or SDS.
      Fourteen (35%) men and 26 (65%) women were included. Using the criteria of 20-dB
      improvement in PTA or 20% improvement in SDS for success, 27.5% (n = 11) showed
      improvement. The mean number of days from onset of symptoms to intratympanic
      therapy was 40 days with a range of 7 days to 310 days. A statistically
      significant difference was noted in those patients who received earlier injection
      (P = .0008, rank sum test). No patient receiving intratympanic dexamethasone
      after 36 days recovered hearing using 20-dB PTA decrease or a 20% increase in
      discrimination as criteria for recovery. Twelve percent (n = 5) of patients in
      the study had diabetes with 20% recovering after intratympanic dexamethasone (not
      significantly different from nondiabetics at 28.6%, Fisher exact test, P = 1.0).
      Comparison to other studies that used differing steroid type, concentration,
      dosing schedule, inclusion criteria, and criteria for success revealed, in many
      instances, a similar overall recovery rate. CONCLUSIONS: Difficulty in proving
      efficacy of a single modality is present in all studies on SNHL secondary to
      multiple treatment protocols, variable rates of recovery, and a high rate of
      spontaneous recovery. Forty percent of patients showed some improvement in SDS or
      PTA after treatment failure. When criteria of 20-dB PTA or 20% is considered to
      define improvement, the recovery rate was 27.5%. Modest improvement is seen with
      the current protocol of a single intratympanic steroid injection of 24 mg/mL
      dexamethasone in patients who failed systemic therapy. Dramatic hearing recovery
      in treatment failures was rarely encountered. No patient showed significant
      benefit from intratympanic steroids after 36 days when using this protocol for
      idiopathic sudden SNHL. If patients injected after 6 weeks are excluded from the
      study, the improvement rate increases from 26.9% to 39.3%. Earlier intratympanic
      injection had a significant impact on hearing recovery, although with any
      therapeutic intervention for sudden SNHL, early success may be attributed to
      natural history. If we further exclude seven patients treated with intratympanic
      steroids within 2 weeks of the onset of symptoms (i.e., study only those patients
      treated with intratympanic dexamethasone between 2 and 6 weeks after onset of
      symptoms), still, 26% improved by 20 dB or 20% SDS. The recovery rates after
      initial systemic failure are higher than would be expected in this treatment
      failure group given our control group (9.1%) and literature review. These
      findings indicate a positive effect from steroid perfusion in this patient
      population.

PMID- 17202925
TI  - Cochlear cytokine gene expression in murine acute otitis media.
AB  - OBJECTIVE: Recurrent acute otitis media (AOM) causes sensorineural hearing loss
      by unknown mechanisms. It is widely accepted that inflammatory cytokines diffuse
      across the round window membrane to exert cytotoxic effects. This study addresses
      whether inner ear cells are capable of expressing genes for inflammatory
      cytokines. STUDY DESIGN: The authors conducted a prospective animal study.
      METHODS: BALB/C mice underwent transtympanic injection of heat-killed Haemophilus
      influenzae to create an acute inflammatory response. These mice were compared
      with a control group in addition to a group of uninjected mice found to have
      otomicroscopic changes consistent with persistent or chronic otitis media. The
      cochleas of these mice were obtained, their RNA harvested, and cytokine gene
      expression analyzed using prefabricated cDNA arrays. RESULTS: Four groups of mice
      (control, 3-day postinjection, 7-day postinjection, and mice with chronic otitis
      media) with five mice in each group were analyzed. Numerous classes of genes were
      found to be upregulated or downregulated by more than twofold. Some genes
      differed from control mice by more than 10-fold. These genes included numerous
      fibroblast growth factors, interleukins, tumor necrosis factors, and colony
      stimulating factors. CONCLUSION: The genes of numerous inflammatory cytokines are
      either up- or downregulated by murine inner ear cells in response to either acute
      or chronic inflammation of the middle ear. This study provides a novel site of
      production of cytokines that may be responsible for the damage seen in
      sensorineural hearing loss.

PMID- 17202926
TI  - Osteonecrosis of the jaw associated with bisphosphonate use: Presentation of
      seven cases and literature review.
AB  - PROBLEM ADDRESSED: Bisphosphonates, pyrophosphate analogs, are strong osteoclast
      inhibitors that are used for osteoporosis and in the treatment of solid tumors
      with bony metastasis. There are growing reports of osteonecrosis associated with
      the nitrogen containing bisphosphonates, Pamindronate and Zolendronic acid
      therapy. Theses cases have been most commonly seen and treated by oral surgeons.
      An untreated maxillary osteonecrosis can lead to pansinusitis, involving the
      otolaryngologist in these patients' care. To the authors' knowledge, this is the
      first case series reported in the otolaryngology literature. PATIENTS AND
      METHODS: A retrospective chart review was conducted on patients presenting to the
      Mount Sinai Hospital Center and at Elmhurst General Hospital between October 2003
      and November 2004 with a history of refractory osteomyelitis of the jaws and
      chronic bisphosphonate therapy. RESULTS: Seven patients were identified with both
      of these conditions. These patients presented with nonhealing ulcers of the
      mandible or maxilla. Four of the patients were on bisphosphonate therapy, and the
      other three had been treated with bisphosphonates. Three of the patients required
      extensive operations to remove the involved bone. One patient required endoscopic
      sinus surgery. CONCLUSIONS: Increasing reports of bisphosphonate associated
      osteomyelitis and the difficulty in treating these patients requires further
      investigation to identify the subset of patients who are at increased risk for
      this process. The optimal and safe duration of treatment with bisphosphonates
      needs to be determined.

PMID- 17202927
TI  - Perioperative management of intracranial aneurysms and otologic disease.
AB  - OBJECTIVE: Diagnosis and treatment of asymptomatic, unruptured intracranial
      aneurysms (UIA) are areas of longstanding controversy in the neurologic and
      neurosurgical literature. Treatment decisions require careful consideration of
      both the potential for aneurysm rupture as well as the risks associated with
      repair. Studies examining the natural history of UIA, the morbidity and mortality
      associated with subarachnoid hemorrhage (SAH), and the various treatment options
      have led to general guidelines for UIA management. In the literature, the
      simultaneous presence of otologic disease and UIA has not been introduced or
      addressed. It is unknown whether surgical treatment of middle ear disease has an
      effect on the natural history of UIA. STUDY DESIGN: Two illustrative patients
      with UIA discovered incidentally on radiographic evaluation of middle ear disease
      are presented. METHODS: Patients were managed according to diagnostic and
      treatment strategies developed and validated in the neurosurgical literature.
      RESULTS: Both patients underwent uneventful endovascular embolization of their
      intracranial aneurysms before middle ear surgery. The intra- and postoperative
      courses were uncomplicated without symptoms related to either their history of
      intracranial aneurysms or the prior embolization. CONCLUSIONS: Application of
      neurosurgical diagnostic and treatment algorithms to otology patients in the
      perioperative setting is appropriate. Established risk factors such as the size
      and location of the intracranial aneurysm, prior SAH, and patient age should
      guide treatment planning in all cases of UIA. Additional research is needed to
      evaluate the influence of otologic procedures on the natural history of UIA. In
      addition, studies are needed to evaluate the role of preoperative screening for
      UIA in otologic surgery candidates.

PMID- 17202928
TI  - Submandibular gland transfer for severe xerophthalmia.
AB  - OBJECTIVE: To report early clinical experience with a new microvascular
      reconstructive procedure for patients with severe xerophthalmia. STUDY DESIGN:
      Retrospective clinical series. METHODS: Patients with severe xerophthalmia were
      referred for treatment after having exhausted all conventional means of
      treatment. The ipsilateral submandibular gland was transferred to the temporal
      fossa, as described by Macleod et al., and revascularized using the superficial
      temporal artery and appropriate vein(s). The submandibular duct was directed to
      the superolateral fornix so that the saliva produced moistened the eye. Results
      and complications were reviewed. RESULTS: Seven microvascular submandibular gland
      transfer procedures were performed in five patients, ages 6 to 54. The etiology
      of severe xerophthalmia was Stevens-Johnson syndrome in four and chemical burn in
      one. Follow-up time was 4 to 20 months. Successful transfer with
      revascularization was achieved in six of seven (86%) cases. Schirmer's test
      scores improved from 1.3 pretransfer to 8.1 posttransfer (P = .005). Patients
      experienced symptomatic relief within 1 month, and the microenvironment of the
      eye surface improved enough to make them candidates for visual restorative eye
      surgery. There were no major complications. CONCLUSIONS: Microvascular
      submandibular gland transfer is an effective approach for correcting severe
      xerophthalmia. The procedure should be within the skills of any reconstructive
      microsurgeon. This procedure offers a unique opportunity for otolaryngologist
      head and neck reconstructive surgeons to help restore vision to this unfortunate
      group of patients.

PMID- 17202929
TI  - Locally advanced tonsillar squamous cell carcinoma: Treatment approach revisited.
AB  - AIMS: The purpose of this study was to review the treatment policy for locally
      advanced stage III and IV squamous cell carcinoma (SCC) of the tonsil at the
      Princess Alexandra Hospital Head and Neck Unit, Brisbane, Australia. MATERIALS
      AND METHODS: The records of 148 patients with curable stage III and IV SCC of the
      tonsil were reviewed from the years 1992 to 2004 inclusive. During this period,
      patients were treated with surgery and postoperative radiotherapy and only
      offered definitive radiation if they were medically or surgically inoperable.
      There were 102 patients treated with surgery +/- postoperative radiotherapy
      (group 1) and 46 patients treated with definitive radiotherapy +/- chemotherapy
      (group 2). The endpoints of locoregional control (LRC), disease specific survival
      (DSS), and overall survival (OS) were studied and prognostic factors were
      investigated with univariate and multivariate analyses. RESULTS: The 5-year OS,
      DSS, and LRC were 57%, 69%, and 84%, respectively. Univariate analyses showed
      that patients in group 1 had a superior OS (69% vs. 41%, P = .007), a trend
      toward improvement in LRC (88% vs. 73%, P = .08), and a nonsignificant
      improvement in DSS (75% vs. 56%, P = .14). There was a greater percentage of
      patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 or less in
      group 1, suggesting selection bias toward the surgical group. Multivariate
      analyses, which adjusted for known prognostic factors, showed that treatment
      group was significant for OS but not for LRC or DSS. CONCLUSIONS: Surgery and
      postoperative radiotherapy continues to provide a superior outcome in locally
      advanced tonsil SCC in patients with surgically resectable disease, good ECOG
      performance status, and medically operable.

PMID- 17202930
TI  - Surfactant protein d expression in chronic rhinosinusitis patients and immune
      responses in vitro to Aspergillus and alternaria in a nasal explant model.
AB  - OBJECTIVES/HYPOTHESIS: Common fungi have been implicated in the pathogenesis of
      chronic rhinosinusitis (CRS) with eosinophilic mucus (EMCRS). Surfactant protein
      (SP)-D plays an important role in the immune response to Aspergillus fumigatus in
      the lungs. We sought to determine whether SP-D is expressed in nasal mucosa and
      investigated the response of SP-D in vitro to fungal allergens. STUDY DESIGN AND
      METHODS: 1) Nasal biopsies from 59 CRS and EMCRS patients, stratified into
      allergic fungal sinusitis (AFS), nonallergic fungal eosinophilic sinusitis
      (NAFES), and nonallergic nonfungal eosinophilic sinusitis (NANFES) were studied
      by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR),
      immunostaining and enzyme-linked immunosorbent assay (ELISA). 2) Nasal tissue
      from three CRS and three NANFES patients was cultured with fungal allergens in a
      nasal explant in vitro model for 24 hours at increasing concentrations and mRNA
      SP-D secreted SP-D protein levels in response to the fungi determined by qRT-PCR
      and ELISA. RESULTS: Staining for SP-D was detected in the submucosal glands from
      the nasal biopsies in all patient groups except for AFS. By ELISA, SP-D was
      undetectable in AFS and decreased in NAFES, NANFES, and CRS compared with
      controls. CRS patients in vitro cultured with Aspergillus and Alternaria
      allergens in a nasal tissue explant model induced up-regulation of SP-D by qRT
      PCR. In contrast, NANFES nasal tissue explants cultured with Aspergillus
      allergens induced down-regulation of SP-D. CONCLUSIONS: We report for the first
      time the expression of SP-D in both diseased and normal nasal mucosa. SP-D
      expression in CRS patients is up-regulated by fungal allergens in an in vitro
      model. These results may provide potential novel therapy for treatment of CRS.

PMID- 17202931
TI  - Impact of intrascalar blood on hearing.
AB  - OBJECTIVE/HYPOTHESIS: The objective of this controlled animal study was to
      evaluate the effects of intrascalar blood on hearing. MATERIAL AND METHODS: Eight
      guinea pigs underwent intrascalar administration of their own blood in one ear
      and control solution in the contralateral ear. Solutions were applied through
      cochleostomy to the scala tympani. Compound action potential (CAP) thresholds
      were determined before administration and at different intervals for 2 months
      thereafter. RESULTS: Immediate deterioration of thresholds was seen mainly in the
      high-frequency range, averaging 27 dB and 20 dB in the study and control groups,
      respectively. At day 3, threshold shifts recovered in the control group but
      remained in the low-frequency range in the study group. An extensive recovery was
      seen in both groups. However, permanent threshold shifts persisted. There was an
      enhanced shift of thresholds of up to 7 dB in the study group. CONCLUSIONS: Even
      small amounts of intrascalar blood seem to cause transient and permanent
      detrimental effects on cochlear function. In procedures involving opening of the
      otic capsule-like stapes surgery and cochlear implantation with hearing
      preservation-minimizing surgical blood admixture to intracochlear compartments
      seems therefore fundamental.

PMID- 17202933
TI  - The surgical learning curve in aural atresia surgery.
AB  - OBJECTIVE: The objective of this retrospective case review is to examine the
      effect of surgical learning on hearing outcomes and complications in congenital
      aural atresia surgery. PATIENTS: Sixty-four consecutive ears (in 60 patients)
      operated on during the period of 1994 to 2004 at a tertiary referral center were
      studied. INTERVENTION(S): Intervention consisted of aural atresiaplasty through
      an anterior approach by the same surgeon (C.S.). MAIN OUTCOME MEASURE(S): Hearing
      outcomes and complication rates were compared between four temporally sequential
      groups of 16 ears. Acceptable hearing and complication rate outcomes were defined
      as results comparable to larger series in the literature. RESULTS: Hearing
      results, in the short term, comparable to larger series were achieved during the
      first group of ears (nos. 1-16). A plateau in the learning curve for short-term
      hearing outcomes was achieved after the first two groups, that is, after 32 ears.
      Hearing outcomes, in the long term (>1 year) comparable to larger series, were
      achieved in the second group of ears (nos. 16-32). The learning curve for long
      term hearing demonstrated a significant improvement in outcomes in the final
      group of 16 ears compared with the first 48 ears. Long-term hearing results for
      the final group show closure of the postoperative air-bone gap to less than 30 dB
      in 94% of cases. Postoperative complication rates were equivalent to larger
      series in the first group of 16 ears and showed no statistically significant
      difference between the four groups. There was one patient with sensorineural
      hearing loss after surgery; there were no anacoustic ears and no facial palsies
      in the study group. CONCLUSIONS: A learning curve of at least 32 ears was
      required to achieve stable short-term hearing results. To achieve stable long
      term hearing results required a learning curve of at least 48 patients in our
      series. Complication rates remained stable throughout the study period.

PMID- 17202932
TI  - Lower eyelid splinting: An alternative to the Frost suture.
AB  - OBJECTIVES: To describe a new method of postoperative eyelid suspension used for
      the prevention of eyelid malposition and to report its efficacy through an
      outcome study. STUDY DESIGN: An outcome study was performed on 10 patients who
      would potentially need postoperative eyelid suspension. Candidates included
      patients with entropion, ectropion, or orbital fractures requiring
      transconjunctival approaches. Patients were photographed pre- and postoperatively
      and followed for signs of eyelid malposition. METHODS: At the conclusion of the
      surgical procedure, a sheet of Xeroform gauze was folded into 6 overlapping
      layers and cut to conform to the shape of the inferior orbital rim. The superior
      edge of the gauze was sutured to the lower eyelid using interrupted 5-0 nylon
      suture. Sutures were placed at the medial and lateral canthi to raise the eyelid
      above the inferior limbus and along the inferior orbital rim. The splint was
      removed between postoperative days 7 and 14. RESULTS: There were no perioperative
      complications related to the surgery or placement of the splint. No cutaneous
      marks persisted after healing. No complications such as shifting of the splint,
      ocular damage, or recurrent eyelid malposition occurred. One patient had
      asymptomatic restriction of lower eyelid elevation on upward gaze, which resolved
      at 6 months. CONCLUSIONS: The lower eyelid splint appears effective in
      maintaining lower eyelid position postoperatively. There were no complications
      with its use, and the splint was tolerated well. Benefits of the splint over the
      Frost suture include less risk of corneal abrasion, ability to check visual
      function, and ability to use the splint bilaterally.

PMID- 17202934
TI  - Role of surgical salvage for regional recurrence in laryngeal cancer.
AB  - OBJECTIVES: The aims of this study were to analyze the pattern of regional
      recurrence in laryngeal cancer, evaluate the role of surgical salvage, and
      identify factors affecting salvage outcome. METHODS: Retrospective analysis was
      conducted on medical records from a 16-year period. Of 463 patients diagnosed
      with laryngeal cancer, 25 patients with regional recurrence managed with salvage
      neck dissection were identified and subject to study. Isolated local recurrences
      and all distant metastases were excluded. RESULTS: All patients were male with a
      median age of 61 years. The overall rate of regional recurrence was 5.4%. Median
      time to regional recurrence was 13 months. Isolated regional recurrence occurred
      in 76% of cases, whereas locoregional recurrence occurred in 24%. A 5-year
      survival rate for patients undergoing neck dissection as salvage management was
      61.2%. Patients with recurrence in the contralateral neck were definitely
      associated with poor prognosis. Although standard statistical significance was
      not met, trends for poorer salvage result were identified in patients with a
      history of local recurrence before regional recurrence, recurrence in a
      previously dissected neck, and recurred node size of 3 cm or above. CONCLUSIONS:
      Our study shows that salvage neck dissection for regional recurrence in laryngeal
      cancer is an acceptable approach. Surgical eradication of disease should be
      warranted whenever possible. Prudent planning of management is mandatory in the
      presence of history of local recurrence before regional recurrence, previously
      dissected neck, large size of recurrent node, and contralateral neck recurrence.

PMID- 17202935
TI  - Influence of upper airway narrowing on the effective continuous positive airway
      pressure level.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to determine the
      relationship between the continuous positive airway pressure (CPAP) titration
      level and upper airway variables in obstructive sleep apnea syndrome (OSAS).
      SUBJECTS AND METHODS: Forty-seven patients suffering from OSAS were enrolled in
      this study. They were asked to answer a questionnaire about nasal stuffiness and
      mouth breathing, and the degree of tonsillar hypertrophy and shape of the
      oropharyngeal inlet were evaluated. The minimal cross-sectional area (MCA) of the
      nasal cavity was measured with acoustic rhinometry, followed by optimal CPAP
      level titration. We compared optimal CPAP levels with body mass index (BMI),
      perceived nasal stuffiness, and anatomic upper airway narrowing. RESULTS: The
      mean CPAP level was 6.32 +/- 2.17 cm H2O. We found a significant correlation
      between CPAP levels and BMI (P = .01), apnea-hypopnea index (P = .015), and the
      degree of tonsillar hypertrophy (P = .011). Furthermore, the CPAP level increased
      significantly with the MCA on the narrow side of the nasal cavity (P = .038) in
      patients with a BMI less than 25. Other variables, such as subjective symptoms
      and anatomic nasal airway occlusion in obese patients (BMI > or = 25), revealed
      no correlation with the CPAP level. CONCLUSIONS: Upper airway occlusion including
      nasal obstruction or tonsillar hypertrophy might increase the effective CPAP
      level.

PMID- 17202936
TI  - Visual screening of oral cavity cancer: The role of otolaryngologists.
AB  - OBJECTIVES: Because most screening was done by dentists, the purpose of this
      prospective cohort study was to evaluate the effectiveness of oral visual
      screening by otolaryngologists. In addition, we wanted to determine which group
      of enrolled patients was at potential risk of contracting oral cancer. METHODS:
      All male patients age > or =18 years who visited our clinic received oral mucosal
      screening. Basic data, including personal habits, were also obtained. A
      multivariate logistic regression model was devised to determine relevant risk
      factors for developing oral cancer. RESULTS: A total of 5,825 patients were
      enrolled in this study. Positive findings were found in 226 patients (3.9%). One
      hundred seventy-two patients received biopsy and 131 patients were proven to have
      oral cancer (sensitivity rate: 76.2%). The results showed that those who smoked,
      consumed alcohol, and chewed betel quid on a regular basis were most likely to
      contract oral cancer (odds ratio = 49.81, 95% confidence interval = 29.38-84.42).
      CONCLUSIONS: The otolaryngologists involved in this study successfully performed
      the oral screening. The sensitivity and specificity rates were both satisfactory.
      We suggest that those who are habitual cigarette smokers, alcohol consumers, and
      betel quid chewers should receive oral mucosal screening regularly so that
      potential oral cancer can be detected as early as possible.

PMID- 17202937
TI  - Autologous fat graft absorption in unilateral paralyzed canine vocal folds.
AB  - OBJECTIVE: The objective of this experimental prospective study on an animal
      model was to determine the rate of autologous fat graft absorption in 24
      paralyzed canine left vocal folds 12 weeks after introduction. METHODS: Forty
      mongrel dogs of both sexes weighing 15 to 20 kg were divided into three study
      groups (SGs) of eight dogs each whose larynges were grafted by vocal fold
      lipoinjection (VFL-SGA), vocal fold lipoinjection plus insulin (VFLi-SGB), and by
      fat graft medialization laryngoplasty (FGML-SGC) and observed for 12 weeks. Two
      control groups (CGs) of eight dogs each were submitted to fat graft medialization
      laryngoplasty (FGML-CG1) and by vocal fold lipoinjection (VFL-CG2), respectively,
      followed by immediate killing. All 40 dogs were submitted to left vagal and
      recurrent laryngeal nerve resection. All animals were confirmed to have a left
      vocal fold paralysis 4 weeks later when 2 mL of autologous fat graft was placed
      inside the left paraglottic space. The larynges were removed at preestablished
      times and studied for remaining fat graft volume by magnetic resonance imaging.
      RESULTS: The mean volume obtained by imaging were 1.9388 mL for CG1, 1.0476 mL
      for CG2, 0.1924 mL for VFL, 0.336 mL for VFLi, and 0.565 mL for FGML. CG1 and CG2
      did not differ significantly from one another but differed from the SGs, with
      statistical analysis suggesting a lower absorption of the fat graft in FGML.
      CONCLUSION: The absorption rate was 82% in SGA, 68% in the SGB, and 71% in SGC.

PMID- 17202938
TI  - The benign lymphoepithelial cyst and a classification system for lymphocytic
      parotid gland enlargement in the pediatric HIV population.
AB  - OBJECTIVES/HYPOTHESIS: The objectives of this study are to present a series of
      parotid gland benign lymphoepithelial cysts (BLEC) in HIV-positive children and
      to propose a three-tiered classification system for HIV-associated lymphocytic
      parotid gland enlargement. STUDY DESIGN: The authors conducted a retrospective
      case series and literature review. METHODS: The authors conducted a retrospective
      chart review of four pediatric patients with HIV-associated parotid gland BLEC
      who presented to a tertiary care university medical center. RESULTS: Four
      pediatric HIV-positive patients (four girls; age range, 7-17 years [mean age,
      12.8 years]) were diagnosed with parotid gland BLEC. Two patients presented with
      acute parotitis and the others presented with asymptomatic enlargement of the
      parotid glands. Three patients had bilateral parotid gland BLEC. The other
      patient demonstrated persistent generalized lymphadenopathy (PGL) of the
      intraparotid and cervical lymph nodes and early BLEC limited to the left parotid
      gland. One patient also displayed parotid gland microcalcifications and cystic
      changes in the adenoids, neither of which have been described previously in the
      setting of HIV-associated BLEC. Computed tomography was performed on all
      patients, and one patient underwent fine needle aspiration to confirm the
      diagnosis. All patients opted for observation and antiretroviral medication
      therapy as long-term treatment. Based on these findings and a review of the
      literature, we propose a three-tiered classification system for lymphocytic
      parotid gland enlargement in the HIV population: 1) PGL, 2) benign
      lymphoepithelial lesions (BLEL), and 3) BLEC. CONCLUSIONS: This series equals the
      largest pediatric series of HIV-associated parotid gland BLEC in the English
      literature. One patient in our series also demonstrated PGL; there were no cases
      of BLEL. A classification system based on morphology is proposed to help resolve
      the confusion in terminology used to describe this entity. Most pediatric HIV
      infected patients with parotid gland BLEC can be treated with observation and
      antiretroviral medication therapy. For others, who are symptomatic or more
      concerned about their cosmetic appearance, sclerotherapy may offer a reasonable
      option. Radiation therapy and surgery should be reserved for select cases.

PMID- 17202939
TI  - Normative values of olfactory function testing using the 'sniffin' sticks'.
AB  - OBJECTIVES: Quantitative olfactory assessment is often neglected in clinical
      practice, although olfactory loss can assist to diagnosis and may lead to
      significant morbidity. "Sniffin' Sticks" is a modern test of nasal chemosensory
      performance that is based on penlike odor-dispensing devices. It consists of
      three tests of olfactory function: odor threshold, odor discrimination, and odor
      identification. The results of this test may be presented as a composite
      threshold-discrimination-identification (TDI) score. The aim of this study was
      first to develop normative data of olfactory function for the Greek population
      using this test and second to relate olfactory performance to age, sex, and side
      examined. STUDY DESIGN: The authors conducted a prospective clinical trial.
      METHODS: A total of 93 healthy subjects were included in the study, 48 males and
      45 females, mean age of 44.5 years (range, 6-84 years). RESULTS: A database of
      normal values for olfactory testing was established for the Greek population.
      Females performed better than males and older subjects performed less efficiently
      in all tests. We also found a right nostril advantage compared with the left.
      Additionally, scores obtained from bilateral presentation were similar with
      scores obtained from the nostril with the better performance. CONCLUSIONS: The
      "Sniffin' Sticks" can be used effectively in the Greek population to evaluate
      olfactory performance. Mean values of olfactory tests obtained were better in
      comparison with data from settings located in central and northern Europe.

PMID- 17202940
TI  - Planned postradiotherapy neck dissection: Rationale and clinical outcomes.
AB  - OBJECTIVES: In this study, we examine pathology results and clinical outcome for
      patients with locoregionally advanced squamous cell carcinoma of the head and
      neck (SCCHN) who present with advanced neck disease and undergo planned
      postradiotherapy neck dissection. STUDY DESIGN: Review of all patients with SCCHN
      treated with primary radiation (or chemoradiation) and postradiotherapy neck
      dissection at the University of Wisconsin between 1992 to 2005 was performed. One
      hundred seven neck dissections were identified in 93 patients, 79 unilateral and
      14 bilateral. All major treatment and outcome parameters were examined with
      particular emphasis on the postradiotherapy neck dissection. RESULTS: Thirty of
      107 neck dissection specimens (28%) showed evidence of residual carcinoma on
      pathologic review. The mean number of lymph nodes identified at neck dissection
      for the entire cohort was 21 per specimen (range, 1-60) with 1.3 nodes per
      positive neck dissection demonstrating residual carcinoma. No correlation was
      found between the type of neck dissection performed and the presence of residual
      nodal disease. Eighty-two evaluated patients (93%) remain free of regional
      disease recurrence, whereas six patients have subsequently manifested neck
      recurrence. Four of the six patients who developed regional recurrence showed
      residual carcinoma in their neck dissection specimen. Five of these patients
      underwent comprehensive neck dissection (levels I-V); one underwent selective
      neck dissection (<levels I-V). CONCLUSION: Approximately one-fourth of the
      patients in this series showed pathologic evidence of residual carcinoma in the
      neck at the time of postradiotherapy neck dissection. The majority of these cases
      showed microscopic residual carcinoma in a single lymph node. Although in the
      early postradiotherapy setting, we cannot accurately predict the viability and
      growth potential of microscopic residual carcinoma in lymph nodes, these
      findings, combined with the modest overall morbidity of selective neck
      dissection, suggest that planned postradiotherapy neck dissection should be
      strongly considered for patients presenting with advanced neck disease. This
      remains a prevailing clinical practice at our institution.

PMID- 17202941
TI  - Supracricoid laryngectomy outcomes: The Johns Hopkins experience.
AB  - OBJECTIVE: To report the oncologic and functional results from our experience in
      performing supracricoid laryngectomy (SCL) for selected patients with laryngeal
      cancer. STUDY DESIGN: Retrospective chart review. METHODS: Twenty-four
      consecutive patients who underwent SCL for laryngeal cancer in our institution
      from December 2000 to March 2006 have been reviewed. Reports of the site and
      extent of tumor, type of reconstruction, preoperative or postoperative
      radiotherapy, and the final histopathologic examination were reviewed. In
      addition, the reports of the preoperative examination, inpatient course, and
      postoperative follow-up were reviewed. RESULTS: A total of 24 patients were
      involved in the study; 19 had tumors involving the glottic region, and 5 patients
      had tumors involving both the glottic and supraglottic regions (transglottic).
      Ten patients had their SCL for postradiotherapy recurrence/persistence of
      disease. Eighteen patients underwent reconstruction through
      cricohyoidoepiglottopexy (CHEP), whereas six patients had cricohyoidopexy (CHP).
      Eleven patients had an arytenoid cartilage resected; 8 of 11 had CHEP, and 3 of
      11 had CHP. All patients had a tracheostomy and percutaneous endoscopic
      gastrostomy (PEG) tube placement performed at the same time as the SCL. The
      median hospital stay period was 6 days. Twenty-three of 24 had successful
      tracheostomy tube decannulation, with a median time to decannulation of 37 days.
      The median time to removal of the PEG tube was 70 days. The complications with
      SCL were postoperative wound infection in two patients (SCL/CHP) and the need for
      completion total laryngectomy secondary to intractable aspiration in one patient
      with SCL/CHP. One patient with SCL/CHEP had a ruptured pexy and subsequently
      underwent a second reconstruction with successful tracheostomy and PEG tube
      removal. One of 24 patients is still PEG tube dependant, and he had postoperative
      radiotherapy. Fifteen patients underwent concurrent neck dissection. None of the
      patients had any local or regional recurrence, with a median follow-up period of
      3 years. All final surgical margins were negative for tumor invasion. Three
      patients had postoperative radiotherapy, two patients because of nodal metastases
      in the excised lymph nodes and one because of perineural invasion on final
      histopathologic examination of the SCL specimen. There were no perioperative
      deaths. CONCLUSION: SCL with CHEP or CHP represents an effective technique that
      can be taught and effectively used to avoid a total laryngectomy while
      maintaining physiologic speech and swallowing in selected patients with advanced
      stage primary laryngeal cancer or recurrent/persistent laryngeal cancer after
      radiotherapy. There is a good functional recovery with acceptable morbidity and
      an excellent oncologic outcome when strict selection criteria are applied and a
      formal swallowing rehabilitation program is followed.

PMID- 17202942
TI  - Sialoendoscopic treatment for radioiodine induced sialadenitis.
AB  - BACKGROUND AND OBJECTIVE: The use of radioiodine (RI) for the ablation of
      residual thyroid tissue and metastatic thyroid cancer lesions after thyroidectomy
      has become established as standard treatment in the management of differentiated
      thyroid cancer and subsequent sialadenitis is the most common complication of RI
      therapy. The purpose of this study was to establish a new treatment modality for
      RI-induced sialadenitis. METHOD: The study group consisted of 115 patients with a
      mean age of 47.7 (range, 24-78) years. All patients received RI therapy after
      total thyroidectomy. The incidence of RI-induced sialadenitis, salivary gland
      involvement, administered RI dose, treatment modality, and result of treatment by
      interventional sialoendoscopy were evaluated. RESULTS: The incidence of RI
      induced sialadenitis was 18% (21/115), with involvement of the parotid more
      frequent than the submandibular gland. The average development period of RI
      induced sialadenitis was 4.8 months. The average RI dosage for the sialadenitis
      group was higher than for the nonsialadenitis group, suggesting that RI-induced
      sialadenitis may be dose related, although the data were not statistically
      significant because of the small numbers in the high-dose group. Conservative
      management was effective in 71% (15/21) of the cases, and interventional
      sialoendoscopy was successful in 50% of those cases that did not respond to
      conservative treatment. The causes of treatment failure in the remaining cases
      were a totally obstructed parotid duct and stenosis at the bifurcation site.
      CONCLUSION: Sialadenitis is the most common complication after RI therapy.
      Sialadenitis was successfully managed by conservative treatment in most cases,
      and interventional sialoendoscopy is an alternative method of treatment in
      selected cases such as in partial ductal stenosis.

PMID- 17202943
TI  - Potential ototoxicity of aluminum in hemodialysis patients.
AB  - OBJECTIVES/HYPOTHESIS: Aluminum (Al) is a neurotoxin in both human and animal
      models. Al accumulation is usually observed in patients with end-stage renal
      disease (ESRD). To clarify whether Al also exhibits toxic effects on the
      specified neural organ of inner ear, we recruited hemodialysis (HD) patients to
      investigate the effect of serum Al level on the auditory physiology. STUDY
      DESIGN: Forty patients in maintenance HD as well as 40 age-matched healthy
      subjects without hearing complaints were enrolled. The auditory function tests,
      including pure-tone audiometry (PTA), distortion-product otoacoustic emissions
      (DPOAEs), and auditory brainstem response (ABR) were performed in all subjects.
      The serum Al levels determined within 3 months of auditory tests were used for
      analysis. RESULTS: High-frequency hearing impairment was the predominant auditory
      dysfunction in HD patients who showed worse high-tone hearing level on PTA and
      diminished amplitudes of DPOAEs at 3 K and 4 K as compared with the controls (P <
      .001). Age was a significant factor determining the auditory dysfunction in both
      HD patients and control subjects. After age correction, serum Al level correlated
      reversely with the amplitude of DPOAEs-2 K (P = .002), but not with amplitudes of
      DPOAEs-3 K, -4 K, hearing levels on PTA, or wave latencies on ABR. CONCLUSION:
      High-frequency hearing impairment is a common presentation in HD patients. Serum
      Al level correlates reversely with the amplitude of DPOAEs-2 K but not those of
      DPOAEs-3 K, -4 K, hearing levels on PTA, and wave latencies on ABR. Possibly, the
      correlation between the Al level and the high-frequency OAE results was obscured
      by the significantly diminished amplitudes of DPOAEs-3 K, -4 K in ESRD patients.
      These results implicate that the effect of Al is mainly of cochlear origin rather
      than of retrocochlear origin.

PMID- 17202944
TI  - Early swallowing problems in a cohort of patients with nasopharyngeal carcinoma:
      Symptomatology and videofluoroscopic findings.
AB  - OBJECTIVE: To study the incidence and the degree of swallowing dysfunction in
      patients with nasopharyngeal carcinoma (NPC) who underwent radiation therapy
      treatment. INSTITUTION: The study was conducted in the Prince of Wales Hospital,
      a tertiary teaching hospital of the Chinese University of Hong Kong. MATERIALS
      AND METHODS: From October 1999 to July 2001, a cohort of 20 consecutive patients
      with newly diagnosed NPC was prospectively studied. Questions about symptoms,
      including swallowing functions, were asked, and head and neck examination
      including oromotor examination was performed in the subjects before radiation
      therapy. All patients were subjected to videofluoroscopy (VFSS) to assess their
      swallowing function. Abnormalities were scored if they were present on two of
      three swallow attempts. The patients were reassessed at 6 months and 12 months
      after radiotherapy by symptom assessment and VFSS. RESULTS: There were 14 male
      and 6 female patients. The mean age was 43.9 years. Nine patients had early
      (stage I and II) disease, whereas 11 patients had advanced (stage III and IV)
      disease. Nine patients were treated by radiation therapy only and 11 patients by
      concurrent chemoirradiation. Ninety-five percent of the subjects had subjective
      dysphagia at 6 and 12 months after radiation therapy. Ninety percent had
      xerostomia, and 80% had to avoid certain foods at 12 months postradiation
      therapy. All subjects had to alternate solid food with fluid intake to facilitate
      swallowing. An average reduction of jaw movement by 1 cm was noted. A large
      proportion of patients had stasis of food in the pharynx (100% in valleculae and
      60% in pyriform fossae) and impaired pharyngeal peristalsis (60%). One quarter of
      patients had laryngeal penetration. CONCLUSIONS: Subjective swallowing
      difficulties were common in patients in the early follow-up period after
      radiation therapy for NPC according to questionnaire assessment. An objective
      swallowing study revealed that swallowing dysfunction was persistent 12 months
      after radiation therapy.

PMID- 17202946
TI  - Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in
      a rat model.
AB  - OBJECTIVE: To investigate the effects of platelet rich plasma (PRP) and fibrin
      sealant (FS) on facial nerve regeneration. STUDY DESIGN: Prospective, randomized,
      and controlled animal study. METHODS: Experiments involved the transection and
      repair of facial nerve of 49 male adult rats. Seven groups were created dependant
      on the method of repair: suture; PRP (with/without suture); platelet poor plasma
      (PPP) (with/without suture); and FS (with/without suture) groups. Each method of
      repair was applied immediately after the nerve transection. The outcomes measured
      were: 1) observation of gross recovery of vibrissae movements within 8-week
      period after nerve transection and repair using a 5-point scale and comparing the
      left (test) side with the right (control) side; 2) comparisons of facial nerve
      motor action potentials (MAP) recorded before and 8 weeks after nerve transection
      and repair, including both the transected and control (untreated) nerves; 3)
      histologic evaluation of axons counts and the area of the axons. RESULTS:
      Vibrissae movement observation: the inclusion of suturing resulted in overall
      improved outcomes. This was found for comparisons of the suture group with PRP
      group; PRP with/without suture groups; and PPP with/without suture groups (P <
      .05). The PRP without suture group had a significantly greater degree of recovery
      than the PPP without suture group (P < .05), but it did not have better
      performance than suture group (P > .05). The movement recovery of the suture
      group was significantly better than the FS group (P = .014). The recovery of
      function of the PRP groups was better than that of the FS groups, although this
      did not reach statistical significance (P = .09). Electrophysiologic testing:
      there was a significantly better performance of the suture group when compared
      with the PRP and PPP without suture groups in nerve conduction velocity (P <
      .05). The PRP with suture group had the best results when compared with the
      suture as well as the PPP with suture groups in duration and latency-2 of MAP (P
      < .05). For the FS groups, no results were found demonstrating a biological
      effect. The PRP with suture group demonstrated the best performance in the
      latency-2 and the area under the curve of MAP when compared with the suture and
      FS with suture groups (P < .05). Histomorphometric analysis: PRP with suture
      demonstrated the greatest increase in axon counts when compared with suture, FS
      with suture, and PPP with suture groups (P < .05). There was no statistically
      significant difference seen in axon diameter. CONCLUSION: The best results for
      the return of function in our rat facial nerve axotomy models occurred when the
      nerve ends were sutured together. At the same time, the data demonstrated a
      measurable neurotrophic effect when PRP was present, with the most favorable
      results seen with PRP added to suture. There was an improved functional outcome
      with the use of PRP in comparison with FS or no bioactive agents (PPP). FS showed
      no benefit over conventional suturing in facial nerve regeneration. Our study
      provides the potential of a new clinical application for PRP in peripheral nerve
      regeneration.

PMID- 17202945
TI  - Reactivation of herpes simplex virus type 1 and varicella-zoster virus and
      therapeutic effects of combination therapy with prednisolone and valacyclovir in
      patients with Bell's palsy.
AB  - OBJECTIVES: To determine whether reactivation of herpes simplex virus (HSV) type
      1 or varicella-zoster virus (VZV) is the main cause of Bell's palsy and whether
      antiviral drugs bring about recovery from Bell's palsy. STUDY DESIGN: Randomized,
      multicenter, controlled study. METHODS: One hundred fifty patients with Bell's
      palsy were enrolled in this study. The patients were randomly assigned to a
      prednisolone group or a prednisolone-valacyclovir group, in whom virologic
      examinations for HSV-1 and VZV were performed by simple randomization scheme in
      sealed envelopes. The recovery rates among various groups were analyzed using the
      Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Reactivation
      of HSV-1, VZV, and both viruses was detected in 15.3%, 14.7%, and 4.0% of
      patients, respectively. There was no significant difference in recovery rates
      between the prednisolone group and the prednisolone-valacyclovir group, although
      recovery in the patients with HSV-1 reactivation tended to be higher in the
      prednisolone-valacyclovir group than in the prednisolone group. There was a
      significant difference in recovery among age groups and between individuals with
      complete and incomplete paralysis. CONCLUSIONS: Reactivation of HSV-1 or VZV was
      observed in 34% of the patients with Bell's palsy. The effect of combination
      therapy with prednisolone and valacyclovir on recovery was not significantly
      higher than that with prednisolone alone.

PMID- 17202947
TI  - Risk factors for wound infection after surgery in primary oral cavity cancer
      patients.
AB  - OBJECTIVES: Few studies have discussed the predictive factors of surgical wound
      infection (WI) in primary oral cavity cancer patients. Therefore, we aimed to
      determine the relevant factors associated with postoperative WI in a large group
      of patients with oral cavity cancers. STUDY DESIGN: Retrospective chart review.
      METHODS: We retrospectively reviewed 1,693 chart records of oral cavity cancer
      patients. Twenty variables were obtained from chart review. Statistical methods
      included descriptive statistics, bivariate analyses, and a multiple logistic
      regression model for investigating the predictive factors for WI. RESULTS:
      Postoperative WI rate was 19.8%. Diabetes mellitus (odds ratio [OR]: 2.511, 95%
      confidence interval [CI]: 1.409-4.475), perioperative blood transfusion (OR:
      4.293, 95% CI: 2.448-7.529), reconstruction with free flap or pectoris major
      myocutaneous flap (OR: 3.682, 95% CI: 1.909-7.102), and postoperative serum
      albumin level less than 2.8 g/dL (OR: 2.853, 95% CI: 1.928-4.221) were all
      independent factors associated with postoperative WI. CONCLUSIONS: Recognition of
      relevant factors can help surgeons to identify those at high risk of WI after
      surgery for primary oral cavity cancer and can enable better management of such
      cases.

PMID- 17202948
TI  - Reduction of complication rate in percutaneous dilation tracheostomies.
AB  - INTRODUCTION: Percutaneous dilation tracheotomy (PDT) is now an accepted
      alternative to surgical tracheotomy in certain patients. We began performing
      these procedures in 2000 and use it regularly in select intensive care unit
      patients requiring prolonged intubation and mechanical ventilation. MATERIALS AND
      METHODS: A retrospective chart review of consecutive PDTs performed in the
      Department of Otolaryngology-Head and Neck Surgery at the John Hopkins Hospital
      between 2002 and 2005 was undertaken. Procedural and postoperative complications
      in an earlier group were compared with those in the later group for both
      frequency and severity. RESULTS: Three hundred eighteen PDTs were performed on
      intensive care patients during this time period. All were performed using the
      Ciaglia method and the Cook Blue Rhino (Cook Medical Products, Bloomington, IN)
      set under direct bronchoscopic visualization. In group A (first 159 patients),
      there were a total of 12 complications (7.5%), including six cases of
      perioperative hemorrhage, whereas in group B (second 159 PDTs), there were seven
      complications (4.4%) with no cases of perioperative hemorrhage. CONCLUSIONS: PDT
      provides an easy and convenient alternative to open tracheotomy (OT) and should
      be added to the otolaryngologist's armamentarium of surgical airway procedures.
      The complication rate of PDT is low and similar to that of open operative
      tracheotomy. However, with experience and the use of strict protocols in both
      patient selection and PDT procedure, the complication rate can be significantly
      reduced further both in frequency and severity, making it even safer than an open
      operative tracheotomy.

PMID- 17202949
TI  - Tumoral calcinosis of the scalp: An unusual site for a rare tumor.
AB  - Tumoral calcinosis is a rare calcifying disorder that is associated with
      deposition of calcium crystals in the periarticular tissues. The mass is most
      often around the hips, elbows, shoulders, and feet but may be occasionally found
      elsewhere. We report a case of multiple sporadic tumoral calcinoses in an adult
      male over the scalp. The scalp as a site of tumoral calcinosis has not been
      previously reported in adults. Previous surgical excisions done on two occasions
      had resulted in recurrence of the tumors. This report highlights the need to
      include tumoral calcinosis in the differential diagnosis of tumors of the scalp.

PMID- 17202950
TI  - First-bite syndrome after resection of the styloid process.
AB  - BACKGROUND: First-bite syndrome (FBS) may occur after operations on
      parapharyngeal space. The main symptom is excruciating pain only after the first
      one or two bites of meals. OBJECTIVE: The objective of this article is to report
      a case of FBS after resection of the styloid process (SP). CASE REPORT: This 51
      year-old woman had a 4-month history of pain on her left neck. Computed
      tomography scan showed a left hypertrophic SP. A diagnosis of Eagle syndrome (ES)
      was then established. She underwent excision of the left SP through a lateral
      cervicotomy. Postoperative recovery was uneventful with pain relief. However, 2
      months postoperatively, intense pain appeared related to the first bite in every
      meal. She received 800 mg carbamazepine per day with good pain control.
      Medication was discontinued after 2 years with no further relapse. CONCLUSIONS:
      This is the first report on FBS after surgical treatment of ES. It is important
      to remember the possibility of the diagnosis and to maintain the patient under
      heavy specific medication, sometimes for longer periods.

PMID- 17202951
TI  - The submental flap: A modified technique for resident training.

PMID- 17202953
TI  - An organizational approach to understanding patient safety and medical errors.
AB  - Progress in patient safety, or lack thereof, is a cause for great concern. In
      this article, we argue that the patient safety movement has failed to reach its
      goals of eradicating or, at least, significantly reducing errors because of an
      inappropriate focus on provider and patient-level factors with no real attention
      to the organizational factors that affect patient safety. We describe an
      organizational approach to patient safety using different organizational theory
      perspectives and make several propositions to push patient safety research and
      practice in a direction that is more likely to improve care processes and
      outcomes. From a Contingency Theory perspective, we suggest that health care
      organizations, in general, operate under a misfit between contingencies and
      structures. This misfit is mainly due to lack of flexibility, cost containment,
      and lack of regulations, thus explaining the high level of errors committed in
      these organizations. From an organizational culture perspective, we argue that
      health care organizations must change their assumptions, beliefs, values, and
      artifacts to change their culture from a culture of blame to a culture of safety
      and thus reduce medical errors. From an organizational learning perspective, we
      discuss how reporting, analyzing, and acting on error information can result in
      reduced errors in health care organizations.

PMID- 17202954
TI  - Employment-at-Will: guidelines for health care managers.
AB  - Employment-at-will is a doctrine that allows an employee or employer to terminate
      the employment relationship at any time for any reason. This doctrine has eroded
      over time with the enactment of federal legislation that gives workers job
      protection. Moreover, various states recognize 3 major exceptions to the
      doctrine. This article examines the historical development of employment-at-will,
      discusses the pros and cons of at-will employment, describes the exceptions to
      the doctrine, and discusses at-will employment issues in the health care
      industry.

PMID- 17202955
TI  - Project planning for health care software implementations.
AB  - It is estimated that 78% of projects fail to meet their original objectives. The
      time spent on project planning will help to improve on this statistic and
      directly yield a more successful project outcome. Based on the experiences of a
      panel of experts and the authors' experiences, this article presents a detailed
      planning guide to increase the chances of success on health care software
      implementations.

PMID- 17202956
TI  - A theoretical model to address organizational human conflict and disruptive
      behavior in health care organizations.
AB  - This article proposes a theoretical model for leaders to use to address
      organizational human conflict and disruptive behavior in health care
      organizations. Leadership is needed to improve interpersonal relationships within
      the workforce. A workforce with a culture of internal conflict will be unable to
      achieve its full potential to delivery quality patient care.

PMID- 17202957
TI  - Improving safety management in health care organizations.
AB  - This article explores reducing workplace accidents and resulting injuries through
      the introduction of better safety management programs in health care
      organizations. It examines the benefits of such programs and discusses causes of
      accidents. It presents components considered necessary for inclusion in an
      effective accident prevention program.

PMID- 17202959
TI  - Halfway there? Check to see if you are: six of 11 health insurance portability
      and accountability act rules are set.
AB  - The Health Insurance Portability and Accountability Act contains 11 rules, 6 of
      which have been released to date. Within each of the rules are numerous actions
      to be implemented. This article reviews those actions and provides health care
      managers with what exactly needs to be done to be in compliance with the Health
      Insurance Portability and Accountability Act effectively and efficiently.

PMID- 17202961
TI  - The hidden costs of caring: what managers need to know.
AB  - Vicarious trauma, compassion fatigue, and secondary traumatic stress all have
      negative costs associated with them that managers of health care agencies need to
      know about. This article describes the causes and effects of vicarious trauma,
      compassion fatigue, and secondary traumatic stress on frontline staff. It also
      examines the negative impact on the functioning of an organization and suggests
      some intervention strategies that leadership might utilize to mitigate these
      negative factors.

PMID- 17202960
TI  - EHR in the UK: shedding some light from a manager's perspective.
AB  - Much has been written recently about the National Health Service electronic
      health record initiative which, from outside the United Kingdom, may sound to
      some like the envy of the world. The National Health Service Connecting for
      Health is the body which now oversees the National Programme for Information
      Technology, which is responsible for delivering England's electronic health
      record or National Care Record Service. Questions have been raised as to whether
      the reported progress toward this admirable goal is an example of spin or
      reality. A health information management professional from the United States, who
      has been working inside the UK eye of the storm, sheds some light from a health
      information management perspective.

PMID- 17202962
TI  - Managing overutilization, quality of care, and sustainable health care outcomes
      in Oman.
AB  - The health care system in Oman is facing a major challenge in managing escalating
      health care costs. One of the reasons for the dramatic increase in health care
      cost is overutilization. This article explores the problem of overutilization in
      Oman and its effect on sustaining the quality of health care. A review of the
      literature is used to develop a comprehensive model in controlling
      overutilization that is more applicable to the health system in Oman. Efforts to
      control costs and increase quality are discussed for possible implementation.

PMID- 17202963
TI  - The end-stage renal disease industry and exit strategies for nephrologists.
AB  - The purpose of this presentation is to identify exit strategies for nephrologists
      under changing conditions in the dialysis market. The end-stage renal disease
      service provider market continues to be highly receptive to consolidation. Taking
      advantage of large economies of scale, large for-profit dialysis chains have
      surpassed independent operators in both number of clinics and total patients.
      With relatively low barriers to entry, new smaller clinics continue to open,
      serving a niche outside the larger chains. Additional competition comes in the
      form of medium players funded by venture capitalists with the added pressure of
      rapid growth and financial return. To ensure market power in both dialysis
      products and managed care negotiation leverage, medium and large service
      providers will continue to seek out attractive acquisition targets. For
      nephrologists to capitalize on investment, clinic and business preparation will
      continue to be the driving force for these divestitures.

PMID- 17202964
TI  - Effective employee counseling for the first-line health care manager.
AB  - Counseling is an important supervisory skill applied for a number of purposes.
      Although the need for counseling is as constant as any need facing the manager, a
      number of commonly encountered barriers often prevent effective counseling. In
      most instances, counseling is a necessary step preceding disciplinary action, and
      it is always an important step in improving employee performance. Although the
      manager may not come to the job with expertise in counseling, counseling can
      nevertheless be learned through practice and the conscientious application of a
      few simple guidelines.

PMID- 17202965
TI  - [Cystic fibrosis: physiotherapy and the risk of cross infection].
AB  - INTRODUCTION: Respiratory infections play a deleterious role in the progression
      of patients suffering from cystic fibrosis. Cross infections and epidemics have
      been documented in these patients, justifying a rigorous prevention regime.
      BACKGROUND: This prevention regime concerns all health workers and rests on
      various recommendations. Segregation of patients and hand hygiene are important
      factors. Respiratory equipment and, more specifically, nebulisers represent a
      potential source of bacterial contamination requiring special attention. In the
      same perspective the risks related to the health care environment, particularly
      the lung function laboratory, should not be ignored. The modalities of prevention
      sometimes have a significant psychological impact that may often be reduced by
      careful explanation. CONCLUSIONS: In view of the time spent in contact with these
      patients the physiotherapists are naturally involved in this prevention regime
      which is an integral part of their treatment.

PMID- 17202966
TI  - [Characteristics of mild asthma: clinical signs and medication use. Position
      statement of the Mild Asthma Working Group (174)].
AB  - OBJECTIVE: To update on the state of knowledge in mild asthma (intermittent and
      persistent mild asthma, according to the GINA classification) review the
      literature, and the position statement of the French Mild Asthma Working Group.
      METHODS: The French Mild Asthma Working Group (11 lung specialists, 4
      paediatricians, 1 pharmacologist, and 1 general practitioner) selected, analysed,
      and summarised the literature on the descriptive epidemiology, physiopathology,
      clinical signs, and management of mild asthma. The position of the working group
      on the descriptive epidemiology (causal factors excluded) and the nature of the
      bronchial inflammation has been presented in a previous article. The present
      article focuses on the clinical features of mild asthma and the use of medication
      for it. RESULTS: Mild asthma was more frequent, more symptomatic, and less well
      controlled in children than in adults. Its generally benign evolution may in some
      (<10%) cases be complicated by severe episodes. Patients with mild persistent
      asthma require controller medication every day: permanent low-dose inhaled
      corticosteroid monotherapy is the reference foundation treatment for persistent
      mild asthma. CONCLUSIONS: The present findings should help clinicians and guide
      them in their approach to managing this condition.

PMID- 17202967
TI  - [Evaluation of pulmonary function in the elderly. Intergroupe Pneumo Geriatrie
      SPLF-SFGG].
AB  - Aging is associated with a progressive decrease in lung function. As a
      consequence of aging, individual's reserve is diminished, but this decrease is
      heterogeneous between individual subjects. Many factors are involved in the
      overall decline in lung function. The prevalence of asthma in the elderly is
      estimated between 6 and 10%. Mortality due to COPD is increasing, especially
      among older subjects. Older subjects are at an increased risk of developing
      chronic diseases such as Parkinson's disease, which can have consequences for
      lung function. Under-nutrition is also common in the elderly and can produce
      sarcopenia and skeletal muscle dysfunction. The presentation of respiratory
      disorders may differ in the elderly, especially because of a lack of perception
      of symptoms such as dyspnea. The impact of bronchodilatators or corticosteroids
      on respiratory function has not been studied in the elderly. Drugs usually used
      for the treatment of hypertension or arrhythmias, which are often observed with
      aging, can have pulmonary toxicity. There is no difference between functional
      evaluation in younger and older subjects but it is more difficult to find
      predicted values for older patients. Performing pulmonary function tests in older
      patients is often difficult because of a higher prevalence of cognitive
      impairment and/or poor coordination. When assessing pulmonary function in the
      elderly, the choice of tests will be depend on the circumstances, with the use of
      voluntary manoeuvres dependent on the condition of the patient.

PMID- 17202968
TI  - [Porto-pulmonary hypertension].
AB  - INTRODUCTION: Porto-pulmonary hypertension (PoPH) is the association of pulmonary
      artery hypertension and portal hypertension. The diagnosis of PoPH is based on
      pulmonary haemodynamic criteria, obtained via right heart catheterisation,
      including an increase in mean pulmonary arterial pressure (> 25 mmHg) and in
      pulmonary vascular resistance (> 240 dyn.s.cm-5). STATE OF THE ART: The exact
      pathophysiological mechanisms of PoPH are unknown. However, since PoPH has been
      reported in patients with non-hepatic portal hypertension, the factor that
      determines the development must be portal hypertension rather than liver disease
      per se. Moreover, no simple relationship has been identified between the degree
      of hepatic impairment and the severity of PoPH. The clinical presentation is non
      specific with haemodynamic failure occurring at the end stage. As a consequence,
      screening by annual transthoracic echocardiography is highly recommended in
      potential liver transplant candidates. Therapy with prostacyclin analogues may
      partially relieve pulmonary arterial hypertension (PAH). Liver transplantation
      has an uncertain effect in PoPH and because PoPH is associated with a high
      perioperative mortality, moderate to severe PoPH remains a contraindication for
      liver transplantation. PERSPECTIVES AND CONCLUSIONS: Recent advances in the
      management of PoPH have improved the prognosis. The safety and efficacy of oral
      endothelin receptor antagonists and oral phosphodiesterase inhibitors is
      currently under evaluation. A therapeutic approach utilising combinations of
      drugs should provide better long-term results.

PMID- 17202969
TI  - [Evaluation of clinical practice in pulmonology: tuberculosis].
AB  - INTRODUCTION: The management of patients affected by tuberculosis raises issues
      including epidemiology, the identification and treatment of disease or infection,
      infection control measures, BCG vaccination and national and international
      strategies against the disease. STATE OF THE ART: BCG vaccination is
      controversial because of its undesirable effects and the conflicting evidence
      from trials. It provides partial but undeniable protection; 50% against all forms
      and 80% against the most severe forms, particularly in children. Vaccination
      strategies (generalised, selective or not at all) provide different cost/benefits
      depending on the population involved and its prior vaccination history. This
      variation in response does not outweigh the ethical and pragmatic considerations
      underlying the current approach of universal vaccination. The directly observed
      therapy, short course (DOTS) strategy has been well evaluated notwithstanding the
      huge potential scope of its global implementation. PERSPECTIVES: A more effective
      vaccine is one of the possible solutions for eliminating tuberculosis. DOTS could
      be usefully implemented in France as part of a strategy to eliminate the disease.
      CONCLUSION: BCG vaccination and elements of DOTS are effective interventions for
      the management of TB.

PMID- 17202970
TI  - [Evaluation of clinical practice in pulmonary oncology: a review of the
      literature].
AB  - INTRODUCTION: Evaluation of clinical practice in pulmonary oncology aims to
      improve both the quality of care and the control of costs. REVIEW OF THE
      LITERATURE: A Medline search of the literature allowed analysis of the published
      studies of the evaluation of clinical practice. They showed that though 82-95% of
      patients with small cell bronchial carcinoma were treated with a combination of
      etoposide and cisplatin, less than half of the patients with non-small cell
      cancer received treatment. VIEWPOINT: Various factors such as age, comorbidity,
      race, socio-economic status and gender affect the treatment decisions. There is
      also a discrepancy between the trial data and clinical practice that could be
      explained by two factors. On one hand advances are not always adopted by doctors
      and on the other hand the patient populations treated may sometimes be different
      from those in the trials. CONCLUSION: Though the number of published studies is
      still low an increase is to be expected on account of the publication of new
      regulations concerning the evaluation of clinical practice and the appropriate
      use of drugs.

PMID- 17202971
TI  - [Pulmonary involvement in polymyositis and dermatomyositis].
AB  - Polymyositis is characterised by an inflammatory reaction in skeletal muscle with
      a variable degree of muscular weakness and associated with skin lesions in the
      case of dermatomyositis. Involvement of the muscles of deglutition and the
      diaphragm may lead to inhalation pneumonia and acute or chronic respiratory
      failure, often hypercapnic. The other respiratory manifestations are diffuse
      interstitial pneumonitis (DIP), usually non-specific, and very occasionally
      pulmonary arterial hypertension. The development of DIP during polymyositis is a
      grave prognostic factor, respiratory involvement being one of the main causes of
      morbidity and mortality. The onset of DIP is acute in between 30 and 47% of
      cases. Anti-synthetase antibodies (particularly anti-JO-1) are positive in about
      75% of cases. Treatment is usually with a combination of immunosuppressants and
      corticosteroids without any immunosuppressants therapy having shown a
      superiority.

PMID- 17202972
TI  - [Smoking in adolescents: prevalence, clinical manifestations, preventive
      measures].
AB  - INTRODUCTION: Since the late 1990s, several French surveys have studied
      perceptions about and the use of tobacco and other drugs among adolescents. This
      enables to track trends in tobacco use at this crucial age. This article presents
      the main epidemiological data gathered since 2000 and also reviews older surveys
      in order to place recent trends in a broader perspective. STATE OF THE ART: Thus,
      tobacco use has been decreasing in adolescents for several years but remains at a
      higher level than in the adult French population or than in many other European
      countries. This pattern is linked with a clearer view of the dangers of tobacco
      in terms of addiction and related harms, compared with alcohol and cannabis.
      PERSPECTIVES: The results vary according to social background and level of
      educational attainment and echo similar trends in adult populations. CONCLUSIONS:
      General population surveys can provide useful data for the monitoring and the
      understanding of trends in tobacco use. They can also provide useful information
      regarding prevention for policy makers and other health professionals.

PMID- 17202973
TI  - [The effects of tobacco on children].
AB  - INTRODUCTION: Smoking remains an important topic. It is estimated that at present
      half the children born in France have been, or will be, exposed to the toxic
      effects of passive smoking. This paper aims to review the evidence of the effects
      of passive smoking, both intra and extra-uterine. STATE OF THE ART: Extra-uterine
      passive smoking is implicated in numerous respiratory (asthma, allergy,
      infections...) and non respiratory diseases (neoplastic, dental, ophthalmic,
      digestive, cardio-vascular and infective). Intra-uterine exposure is even more
      dangerous and leads to abnormalities of the pregnancy (placental abnormalities,
      prematurity...), of the foetus (behavioural problems, malformations) and long
      term problems for the unborn child. Passive smoking is responsible for pulmonary
      morphological abnormalities (pulmonary hypoplasia, reduction in elasticity,
      increased deposition of collagen and alteration of alveolar structure) and
      functional disorders (reduced compliance, increased airways resistance, bronchial
      hyperreactivity). Finally it causes a disturbance of respiratory control,
      promoting all the factors responsible for sudden cot death. CONCLUSIONS: The ill
      effects of passive smoking fully justify efforts to inform and persuade the
      medical profession of its duty to fight this scourge.

PMID- 17202974
TI  - [Occupational hypersensitivity pneumonitis].
AB  - INTRODUCTION: Hypersensitivity pneumonitis (HP) is a granulomatous disease of the
      lungs due to immune reactions following chronic inhalation of organic dusts or
      chemicals especially encountered in the occupational environment. The main
      purpose of this review is to report current concepts regarding aetiologies,
      epidemiology, diagnosis, treatment as well as legal aspects of HP. STATE OF THE
      ART: The following aspects will be focused: (1) increase in new etiological
      circumstances, especially occupational and news antigens, (2) for diagnosis, the
      major contribution of chest high resolution CT scan which often shows
      characteristic images but also recent developments in simple diagnostic criteria
      that may be used for an epidemiological approach, (3) importance of bronchial
      obstruction and even emphysema as a long term sequelae, finally (4) the
      possibility of continuing occupational activities in certain circumstances where
      preventive measures can be used. PERSPECTIVES: The increasing knowledge of
      etiological agents and circumstances as well as the development of secondary and
      especially primary preventive measures should lead to reduce the frequency of
      this disease and of its medico-social consequences.

PMID- 17202975
TI  - [Epidemiology and etiologic agents of occupational asthma].
AB  - INTRODUCTION: Occupational asthma is, by definition, a disease that can be
      prevented through appropriate protective strategies. Epidemiological information
      is required to guide these interventions, and we here examine epidemiological
      data on the burden, causes, and risk factors for this condition. STATE OF THE
      ART: Population-based surveys indicate that approximately 15% of adult asthma is
      attributable to the workplace environment. The most common occupational agents
      implicated include flour, isocyanates, latex, and persulphate salts. The
      occupations in which occupational asthma has been most commonly reported are
      bakers, spray painters, health-care workers, hairdressers, and cleaners. The
      level of exposure to sensitizing agents seems to be the most relevant risk
      factor. Atopy is a significant risk factor only for the development of
      sensitization to high molecular weight agents. The role of other individual
      determinants, such as genetic factors, has been less consistently established.
      Occupational asthma is associated with a substantial adverse impact on the
      employment and financial status of affected workers. PERSPECTIVES: Methodological
      improvements are required in order to distinguish more accurately between
      occupational and work-exacerbated asthma. Further investigations of the
      effectiveness of primary and secondary preventive interventions are also needed.

PMID- 17202976
TI  - [Recurrent varices at the groin and popliteal fossa after surgical treatment].
AB  - Patients who undergo surgery involving the groin and the popliteal fossa often
      develop recurrent varices which require careful management. Several surveys using
      various classification systems have estimated the prevalence of recurrent varices
      after groin and popliteal surgery. Patients may seek medical care for various
      reasons: unsightly recurrent varicose veins, vein-related symptoms, appearance of
      cutaneous or subcutaneous changes, concerns about the health risk related to
      their veins or limitation of activity. Recurrent varices may also be found at
      routine follow-up examinations. An analysis of recurrence at this location
      reveals three main mechanisms: incomplete resection of the saphenofemoral or
      saphenopopliteal junctions in patients with an initially incompetent terminal
      valve. The persisting reflux feeds the tributaries connected at the saphenous
      stump; the second mechanism is related to neovascularisation that reconnects the
      deep venous system with the superficial network; the neo-veins are valveless.
      This phenomenon appears to be more frequent when the resection of the saphenous
      vein ending has been complete; the third mechanism is due to a tactical error;
      the refluxive pelvic veins that had not been diagnosed feed the varices. Duplex
      scanning identifies the different possible mechanisms and provides anatomical and
      hemodynamic data. Interventional treatment methods after varices recurrence are
      redosurgery, sclerotherapy and pelvic vein embolization when they are at issue.
      All these methods are described in details. Results provided by these treatments
      are analysed. Unfortunately no randomized control study enables grade A or B
      recommendations. Personally we suggest that ultrasound guided foam sclerotherapy
      should be the first-line treatment except when duplex scanning reveals an intact
      incompetent saphenous stump at the saphenofemoral junction or/and
      saphenopopliteal junction with a massive reflux filling the varicose network.

PMID- 17202977
TI  - [Elastic stockings and compression therapy, arguments favoring more rational
      use].
AB  - Elastic stockings and compression therapy are often considered as a major tool in
      the prevention and in the treatment of chronic venous insufficiency and of
      lymphedema. Nevertheless we must note that this therapeutic option is both
      underused and misused. We discuss the reasons for this paradox and the expected
      modes of action and pathophysiological benefits, and finally propose a
      prescription guide (indications, dosage, practice details) for a rational use of
      elastic stockings and compression therapy.

PMID- 17202979
TI  - [Screening for abdominal aortic aneurysm and surveillance of small abdominal
      aortic aneurysms, rationale and recommendations of the French Society for
      Vascular Medicine. Final document].

PMID- 17202978
TI  - [Imaging of acute stroke].
AB  - Acute stroke patients represent an important diagnostic and therapeutic
      challenge. Patients with brain damage in the ischemic, but not yet infarcted,
      phase have the greatest potential for recovery. Here we review the most commonly
      employed diagnostic tools that are currently used before stroke therapy. While
      computed tomography is pertinent to differentiate ischemic from hemorrhagic
      stroke, this technique cannot be used as an etiological screening too. The
      ischemic origin of symptoms can be confirmed with magnetic resonance imaging
      which also contributes to for therapeutic decision making, prognosis assessment
      and etiological screening.

PMID- 17202980
TI  - [Traumatic unilateral renal artery thrombosis and protein C deficiency. A case
      report].
AB  - Post traumatic renal artery thrombosis is rarely described in the literature.
      This pathology can result from stretch injury to inelastic intima of the renal
      artery, or by the direct flow to the abdomen causing compression injury to the
      renal artery against the vertebral column. However, the association of this
      pathology with hematologic diseases (in particular protein C deficit) was never
      described. We report an observation of a 28-year-old man with an uneventful
      history who was admitted to the intensive care unit for traumatic head injury
      associated with post traumatic renal artery thrombosis requiring nephrectomy. The
      etiologic investigation of this thrombo-embolic complication reveals a protein C
      deficit. Our patient was improved under treatment. This original observation
      confirms that post traumatic renal artery thrombosis can be associated with
      hematologic diseases (in particular protein C deficit).

PMID- 17202981
TI  - [Takayasu's arteritis associated with acute myeloblastic leukemia].
AB  - INTRODUCTION: We present one patient with acute myeloblastic leukemia diagnosed
      two months after the onset of Takayasu's arteritis. EXEGESIS: A 21-year old woman
      with a previous history of erythema nodosum and episcleritis was admitted for a
      left cervical mass. Diagnostic imaging showed an aneurism of the left
      extracranial internal carotid and a stenosis of the left subclavian artery.
      Histological findings of the carotid aneurism revealed a granulomatous giant cell
      arteritis consistent with Takayasu's arteritis. Two weeks after, she was
      discharged, elevated white cell count (440.000/mm3 ) was disclosed. A bone marrow
      aspirate documented an acute myeloid leukemia. The patient died of intracerebral
      hemorrhage. CONCLUSION: Leucocytoclastic vasculitis and polyarteritis nodosa
      occur in acute myeloid leukemia, but the association with Takayasu's arteritis is
      new. In our knowledge, only two documented cases of Takayasu's arteritis in
      association with acute myeloblastic leukemia have been published.

PMID- 17202982
TI  - [Aneurysm of the coeliac trunk. A case report].
AB  - Aneurysm of the coeliac artery is a rare vascular problem. The most serious
      clinical complication of coeliac artery aneurysm is rupture. Because of this,
      surgery is traditionally recommended. This paper presents a case of a coeliac
      artery aneurysm treated by open surgery.

PMID- 17202983
TI  - [Pseudoaneurysm of the abdominal aorta due to retroperitoneal lymph nodes,
      diagnosed by Doppler ultrasound and treated by embolization].
AB  - OBJECTIVE: To report a case of pseudoaneurysm of the abdominal aorta due to
      retroperitoneal enlarged lymph nodes. MATERIALS AND METHODS: A 40 years old
      patient, with known sarcoma and metastatic retroperitoneal lymph nodes was
      referred for abdominal ultrasound because severe abdominal pain after defecation.
      RESULTS: The Doppler examination revealed magma of retroperitoneal lymph nodes
      surrounding the abdominal aorta inside of which a saccular collection of
      circulating blood, communicating with the aorta, was detected. The spectrum
      registered in the channel revealed a bidirectional flow compatible with a
      pseudoaneurysm. MR angiography confirmed the diagnosis. Successful occlusion was
      done by coil embolization. CONCLUSION: Pseudoaneurysms of the abdominal aorta are
      very rare. We report the first case of pseudoaneurysm arising in retroperitoneal
      lymph nodes. Diagnosis by Doppler ultrasound allowed a rapid treatment by
      embolization.

PMID- 17202985
TI  - [Tinnitus in young adults].

PMID- 17202987
TI  - [Infraglottic stricture in newborns].

PMID- 17202986
TI  - [Fluctuating deafness].

PMID- 17202988
TI  - [Botulinium toxin in ENT].

PMID- 17202989
TI  - [Endonasal endoscopic approach in the treatment of sino-nasal inverted
      papillomas].
AB  - INTRODUCTION: Sino-nasal inverted papilloma is a rare benign tumor of the nasal
      fossa and the paranasal sinuses for which the successful surgical treatment by an
      endonasal approach has been corroborated in the literature. Nevertheless, the
      authors aim in this study to evaluate the advantages and the limits of this
      approach, to analyse its failures and its recurrences, and to define the
      indications for using it with the external or dissimulated approach. MATERIAL AND
      METHODS: 42 patients presenting with a sino-nasal inverted papilloma and treated
      surgically over a ten year period were included in this retrospective study. The
      operative technique was chosen as a function of the endonasal and radiological
      examination results (CT scan and MRI). Follow-up was over one year for all
      patients. RESULTS: Twenty eight patients were operated exclusively through an
      endoscopic endonasal approach. Fourteen patients were operated using a combined
      approach, associating either a vestibular (9 cases), a paralateral nasal (3
      cases) or a fronto-orbital (2 cases) approach with endonsal endoscopy. In two
      cases, an associated squamous cell carcinoma was found. We observed a recurrence
      in 9.5% of the all cases and in 14.2% of the patients treated using a combined
      approach. CONCLUSIONS: Endoscopic endonasal surgery is a validated surgical
      approach for the treatment of sino-nasal inverted papilloma in that total tumor
      removal is possible. This approach is particularly indicated in medially-situated
      papillomas without frontal or maxillary extension. In all other cases,
      associating an external or dissimulated approach is usually necessary.

PMID- 17202990
TI  - [Predictive factors of facial palsy of the acoustic neurinoma after retrosigmoid
      surgery: 230 cases].
AB  - OBJECTIVES: To determine predictive factors influencing postoperative facial
      palsy during retro sigmoid approach in vestibular schwannoma surgery. MATERIAL
      AND METHODS: Retrospective study over 230 patients with vestibular schwannoma,
      mostly stade I and II, operated by retro sigmoid approach, by the same oto neuro
      chirurgical team between 1993 and 2004. Pre and post operative parameters taken
      into consideration: quantitative: age and sex, audiometric parameters, duration
      of clinical symptoms; qualitative: tumor anatomic factors and facial nerve
      function according to House Brackmann classification. RESULTS: 8 days after
      surgery, 92% of patients have a normal or subnormal facial nerve function, 5% a
      facial paresis and 3% a paralysis. After one year, only 4% of patients still have
      a grade III to VI paralysis. Latency of vertigo with facial nerve paralysis is
      4.33 vs. 1.97 year in absence of paralysis. Hearing conservation is 85% without
      facial nerve paralysis vs. 58% with facial nerve paralysis; Wave III latency
      (PEAP) with facial nerve paralysis is 4.54 vs. 4.28 ms if not. CONCLUSION:
      Significant predictive factors of facial nerve palsy outcome are: age, post
      surgery hearing conservation, wave III latency, difficulty in tumor dissection,
      vertigo latency.

PMID- 17202991
TI  - [Slide tracheoplasty in congenital tracheal stenosis].
AB  - OBJECTIVES: Slide Tracheoplasty has progressively become the gold standard in the
      management of long-segment tracheal stenosis in children and infants. However, in
      certain situations this operation might become difficult and others techniques
      might be preferred. MATERIAL AND METHODS: Five patients, 1 to 6 month old had
      surgery by our team, for complex tracheal stenosis between 2001 and 2005.
      Tracheal hypoplasia was considered complex because it was associated to either:
      an acquired critical stenosis, a cricoid stenosis, a bronchial stenosis, a
      tracheal bronchus or associated to oesophageal atresia and severe tracheomalacia.
      All of them have been treated by a modified slide tracheoplasty. RESULTS: The
      postoperative status required an average of 15 days in ICU, including 8 days of
      ventilation. Two patients had laryngeal nerve injury. Medium term follow up (27
      months) demonstrated no need for re-intervention, good potential growth and
      normal child activity. CONCLUSIONS: Slide tracheoplasty can provide good results
      in certain cases of severe and complex tracheal hypoplasia in infants.

PMID- 17202992
TI  - [Parathyroid adenoma: surgical strategy].
AB  - OBJECTIVES: The purpose of this study is to reach a better understanding in the
      handling of parathyroid adenomas, and to emphasize the importance of pre
      operatory explorations in order to establish the best surgical approach and its
      cost. MATERIAL AND METHODS: We are using a retrospective study of 51 patients
      that underwent surgery in our department between the years 1997 and 2002, for the
      treatment of primary hyperparathyroidism. Every patient received to a pre
      operatory exploration in order to localize the parathyroid tumors, including
      cervical echography in 51 of the cases, and a sestamibi scintigraphy in 49 of the
      cases. Two surgical procedures were performed: unilateral approach, and bi
      lateral approach. RESULTS: The implementation of a systematic pre-surgical
      checkup allowed for unilateral surgery in 76% of the patients (39 out of 51),
      from which 31% (12 out of 39) under local anesthesia. CONCLUSIONS: The accuracy
      of the pre-operatory explorations in order to localize the parathyroidian tumors
      in regard to HPTP, allows for precise surgery via unilateral approach under local
      anesthesia. The benefits are significant with shorter procedure time, shorter
      patient hospitalization, and lower risks for complications. The pre-operatory
      explorations also decrease the total cost of the procedure and are a critical
      tool for the surgeon.

PMID- 17202993
TI  - [Traumatic luxation of the stapes: radiology and surgical outcome].
AB  - OBJECTIVES: To describe the value of high resolution computed tomography scan
      (HRCT scan) in post traumatic hearing loss. METHOD: HRCT scan of the temporal
      bone in millimetric cut with axial and coronal views was performed. RESULTS: CT
      scan confirmed pneumolabyrinth with intact stapes depressed deeply into the
      vestibule. Surgical exploration was performed and the stapes was gently removed
      from the vestibule. CONCLUSION: CT scan confirmed the diagnosis and studied the
      stapes integrity. Hearing deteriorated postoperatively is increased in case of
      stapes fracture. When a luxation of the stapes into the vestibule is suspected,
      it is important to determine how deeply and whether it is fractured. When such a
      case is encountered, high resolution CT scan of the temporal bone must be
      performed to confirm the diagnosis and to confirm integrity of the stapes.

PMID- 17202994
TI  - [How to perform laryngeal fibroscopty in children].

PMID- 17202995
TI  - [How to obtain a digital photograph in ENT].

PMID- 17202996
TI  - [Who am I: F... the ear-nose-and-throat story].

PMID- 17202997
TI  - Significant variation in haplotype block structure but conservation in tagSNP
      patterns among global populations.
AB  - The initial belief that haplotype block boundaries and haplotypes were largely
      shared across populations was a foundation for constructing a haplotype map of
      the human genome using common SNP markers. The HapMap data document the
      generality of a block-like pattern of linkage disequilibrium (LD) with regions of
      low and high haplotype diversity but differences among the populations. Studies
      of many additional populations demonstrate that LD patterns can be highly
      variable among populations both across and within geographic regions. Because of
      this variation, emphasis has shifted to the generalizability of tagSNPs, those
      SNPs that capture the bulk of variation in a region. We have examined the LD and
      tagSNP patterns based upon over 2000 individual samples in 38 populations and 134
      SNPs in 10 genetically independent loci for a total of 517 kb with an average
      density of 1 SNP/5 kb. Four different 'block' definitions and the pairwise LD
      tagSNP selection algorithm have been applied. Our results not only confirm large
      variation in block partition among populations from different regions (agreeing
      with previous studies including the HapMap) but also show that significant
      variation can occur among populations within geographic regions. None of the
      block-defining algorithms produces a consistent pattern within or across all
      geographic groups. In contrast, tagSNP transferability is much greater than the
      similarity of LD patterns and, although not perfect, some generalizations of
      transferability are possible. The analyses show an asymmetric pattern of tagSNP
      transferability coinciding with the subsetting of variation attributed to the
      spread of modern humans around the world.

PMID- 17202998
TI  - The pitfalls in the development of biologic therapy.

PMID- 17202999
TI  - The future of imaging in monitoring biologic therapy.

PMID- 17203001
TI  - Do antirheumatic drugs increase the risk of acute myocardial infarction?

PMID- 17203000
TI  - Alendronate versus alfacalcidol in the prevention of glucocorticoid-induced bone
      loss.

PMID- 17203002
TI  - Tumor necrosis factor antagonists and cancer in patients with rheumatoid
      arthritis.

PMID- 17203003
TI  - Frequency of COX2-inhibitor use in the clinic prior to market withdrawals.

PMID- 17203004
TI  - Does daily calcium supplementation reduce the risk of clinical fractures in
      elderly women?

PMID- 17203005
TI  - Strategies for primary and secondary prevention of Lyme disease.
AB  - Lyme disease (borreliosis) incidence continues to increase despite a growing
      knowledge of primary and secondary prevention strategies. Primary prevention aims
      to reduce the risk of tick exposure and thereby decrease the incidence of new
      Lyme disease cases. Secondary prevention targets the development of disease or
      reduces disease severity among people who have been bitten by infected ticks.
      Numerous prevention strategies are available, and although they vary in cost,
      acceptability and effectiveness, uptake has been universally poor. Research in
      areas where Lyme disease is endemic has demonstrated that despite adequate
      knowledge about its symptoms and transmission, many people do not perform
      behaviors to reduce their risk of infection. New prevention strategies should aim
      to increase people's confidence in their ability to carry out preventive
      behaviors, raise awareness of desirable outcomes, and aid in the realization that
      the necessary skills and resources are available for preventive measures to be
      taken. In this article we evaluate the prevention and treatment strategies for
      Lyme disease, and discuss how these strategies can be implemented effectively. As
      many patients with Lyme disease develop arthritis and are referred to
      rheumatologists it is important that these health-care providers can educate
      patients about disease-prevention strategies.

PMID- 17203006
TI  - Drug Insight: resistance to methotrexate and other disease-modifying
      antirheumatic drugs--from bench to bedside.
AB  - The chronic nature of rheumatoid arthritis (RA) means that patients require drug
      therapy for many years. Many RA patients, however, have to discontinue treatment
      because of drug-related toxic effects, loss of efficacy, or both. The underlying
      molecular cause for loss of efficacy of antirheumatic drugs is not fully
      understood, but it might be mediated, at least in part, by mechanisms shared with
      resistance to anticancer drugs. This Review outlines molecular mechanisms that
      could be involved in the onset of resistance to, or the loss of efficacy of,
      disease-modifying antirheumatic drugs in RA patients, including methotrexate,
      sulfasalazine, chloroquine, hydroxychloroquine, azathioprine, and leflunomide.
      The mechanisms suggested are based on findings from experimental laboratory
      studies of specific drug-uptake and drug-efflux transporters belonging to the
      superfamily of multidrug-resistance transporters, alterations in intracellular
      drug metabolism, and genetic polymorphisms of drug transporters and metabolic
      enzymes. We also discuss strategies to overcome resistance and the current
      clinical studies aiming to predict response and risk of toxic effects. More in
      depth knowledge of the mechanisms behind these features could help facilitate a
      more efficient use of disease-modifying antirheumatic drugs.

PMID- 17203007
TI  - Technology Insight: the role of color and power Doppler ultrasonography in
      rheumatology.
AB  - An increasing number of rheumatologists have access to ultrasound equipment that
      provide both color and power Doppler modes, which can be used to investigate
      musculoskeletal and vascular pathologies. Musculoskeletal Doppler ultrasonography
      can be used to estimate levels of inflammation, to document the anti-inflammatory
      effect of agents such as corticosteroids and tumor necrosis factor inhibitors, to
      differentiate between inflammatory and degenerative disease, and to distinguish
      between normal and inflamed joints in cases of minor synovial swelling. Vascular
      Doppler ultrasonography can be used to determine organ involvement in small
      vessel vasculitides, to delineate aneurysms in vasculitides of medium-sized
      arteries, and to assess the characteristic findings in large-vessel vasculitis.
      Numerous studies, including a meta-analysis, have been published on the use of
      temporal-artery ultrasonography for the diagnosis of giant cell arteritis. Duplex
      ultrasonography is a sensitive approach for detecting characteristic edematous
      wall swellings in active temporal arteritis and for assessing vasculitis of the
      axillary arteries (large-vessel giant cell arteritis) in patients with suspected
      temporal arteritis, polymyalgia rheumatica, or fever of unknown origin. Duplex
      ultrasonography can also be used to assess vasculitis of subclavian and carotid
      arteries in younger patients with Takayasu's arteritis and acute finger artery
      occlusions in patients with small-vessel vasculitides.

PMID- 17203010
TI  - Environmental influence on the genetic correlations between life-history traits
      in Caenorhabditis elegans.
AB  - Empirical evidence is mounting to suggesting that genetic correlations between
      life-history traits are environment specific. However, detailed knowledge about
      the loci underlying genetic correlations in different environments is scant.
      Here, we studied the influence of temperature (12 degrees C and 24 degrees C) on
      the genetic correlations between egg size, egg number and body mass in the
      nematode Caenorhabditis elegans. We used a quantitative trait loci (QTL) approach
      based on a genetic map with evenly spaced single nucleotide polymorphism markers
      in an N2 x CB4856 recombinant inbred panel. Significant genetic correlations
      between various traits were found at both temperatures. We detected pleiotropic
      or closely linked QTL, which supported the negative correlation between egg size
      and egg number at 12 degrees C, the positive correlation across temperatures for
      body mass, and the positive correlation between body mass and egg size at 12
      degrees C. The results indicate that specific loci control the covariation in
      these life-history traits and the locus control is prone to environmental
      conditions.

PMID- 17203008
TI  - Mechanisms of Disease: leukotrienes and lipoxins in scleroderma lung disease-
      insights and potential therapeutic implications.
AB  - Scleroderma interstitial lung disease (SLD) is a leading cause of morbidity and
      mortality in patients with systemic sclerosis. Although the pathogenesis of SLD
      is not clear, excessive fibrosis and inflammatory cell infiltration are the main
      histologic features of this disorder. Leukotrienes and lipoxins are two
      functionally different classes of lipoxygenase-derived eicosanoids. Leukotrienes
      are potent proinflammatory mediators and directly and indirectly stimulate
      fibroblast chemotaxis, proliferation, and collagen synthesis. Lipoxins counter
      regulate the proinflammatory actions of leukotrienes and activate resolution of
      the inflammatory response. In addition, lipoxins inhibit growth-factor-induced
      fibroblast proliferation and collagen synthesis. Studies using bronchoalveolar
      lavage have revealed that there is an overproduction of proinflammatory and
      profibrotic leukotrienes in the lungs of patients with SLD, and that leukotriene
      levels correlate with inflammatory indices within the lungs. Moreover, the
      increased levels of leukotrienes in these patients are not balanced by an
      upregulation of anti-inflammatory and antifibrotic lipoxins. Unopposed actions of
      leukotrienes might, therefore, induce chronic inflammation and fibrosis in the
      lungs of SLD patients. Accordingly, pharmacologic correction of a leukotriene
      lipoxin imbalance using leukotriene inhibitors or lipoxin analogs might be a new
      approach to the treatment of SLD.

PMID- 17203009
TI  - Mechanisms of Disease: the role of high-mobility group protein 1 in the
      pathogenesis of inflammatory arthritis.
AB  - High-mobility group protein 1 (HMG1) is a nonhistone nuclear protein that is a
      prototype of a dual-function alarmin whose immune activity is dependent upon its
      cellular location. Inside the cell, HMG1 binds to DNA and has a role in
      transcriptional regulation. Outside the cell, HMG1 acts as a cytokine and has
      activities that resemble those of tumor necrosis factor. The cytokine activities
      of HMG1 become manifest when this protein translocates from the nucleus to the
      cytoplasm and, eventually, into the external milieu; this translocation occurs
      during cell activation and cell death. Given its cytokine activity, HMG1 has been
      implicated in the pathogenesis of a broad range of immune-mediated diseases
      including arthritis. The role for this protein in arthritis was established by
      observations of the expression of HMG1 in synovial tissue of patients with
      rheumatoid arthritis as well as in the joints of animals used to model arthritis.
      Furthermore, in the mouse model of collagen-induced arthritis, treatment with
      antibodies to HMG1 or to an inhibitory domain of HMG1 can attenuate joint
      inflammation and damage. These studies identify a novel pathway in the
      pathogenesis of inflammatory arthritis, as well as a new target for biologic
      therapy.

PMID- 17203011
TI  - The effect of catecholamine depletion by alpha-methyl-para-tyrosine on measures
      of cognitive performance and sleep in abstinent MDMA users.
AB  - (+/-) 3, 4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug of
      abuse and a brain serotonin (5-HT) neurotoxin in animals. Growing evidence
      suggests that humans who use MDMA recreationally can also develop 5-HT neurotoxic
      injury, although functional consequences have been difficult to identify. Twenty
      five abstinent MDMA users and 23 non-MDMA using controls were studied to
      determine whether pharmacologic depletion of brain catecholamines by alpha-methyl
      para-tyrosine (AMPT) would differentially effect MDMA users on measures of
      cognition and sleep, two processes dually modulated by brain serotonergic and
      catecholaminergic neurons. During a 5-day in-patient study, all subjects
      underwent formal neuropsychiatric testing, repeated computerized cognitive
      testing, and all-night sleep studies. At baseline, MDMA users had performance
      deficits on tasks of verbal and visuospatial working memory and displayed
      increased behavioral impulsivity on several computerized tasks, reflecting a
      tendency to perform quickly at the expense of accuracy. Baseline sleep
      architecture was also altered in abstinent MDMA users compared to controls. AMPT
      produced differential effects in MDMA users compared to controls on several
      cognitive and sleep measures. Differences in cognitive performance, impulsivity,
      and sleep were significantly correlated with MDMA use. These data extend findings
      from earlier studies demonstrating cognitive deficits, behavioral impulsivity,
      and sleep alterations in abstinent MDMA users, and suggest that lasting effects
      of MDMA lead to alterations in the ability to modulate behaviors reciprocally
      influenced by 5-HT and catecholamines. More research is needed to determine
      potential relationships between sleep abnormalities, cognitive deficits and
      impulsive behavior in abstinent MDMA users.

PMID- 17203012
TI  - Supersensitivity to amphetamine in protein kinase-C interacting protein/HINT1
      knockout mice.
AB  - Protein kinase C interacting protein/histidine triad nucleotide binding protein 1
      (PKCI/HINT1) is a member of the histidine triad protein family. Although this
      protein is widely expressed in the mammalian brain including mesocorticolimbic
      and mesostriatal regions, its physiological function in CNS remains unknown.
      Recent microarray studies reported decreased mRNA expression of PKCI/HINT1 in the
      frontal cortex of individuals with schizophrenia, suggesting the possible
      involvement of this protein in the pathophysiology of the disease. In view of the
      documented link between dopamine (DA) transmission and schizophrenia, the present
      study used behavioral and neurochemical approaches to examine the influence of
      constitutive PKCI/HINT1 deletion upon: (i) basal and amphetamine (AMPH)-evoked
      locomotor activity; (ii) DA dynamics in the dorsal striatum, and (iii)
      postsynaptic DA receptor function. PKCI/HINT1(-/-) (KO) mice displayed lower
      spontaneous locomotion relative to wild-type (WT) controls. Acute AMPH
      administration significantly increased locomotor activity in WT mice;
      nonetheless, the effect was enhanced in KO mice. Quantitative microdialysis
      studies revealed no alteration in basal DA dynamics in the striatum or nucleus
      accumbens of KO mice. The ability of acute AMPH to increase DA levels was
      unaltered indicating that function in presynaptic DA neurotransmission in these
      regions do not underlie the behavioral phenotype of KO mice. In contrast to WT
      mice, systemic administration of the direct-acting DA receptor agonist
      apomorphine (10 mg/kg) significantly increased locomotor activity in KO mice
      suggesting that postsynaptic DA function is altered in these animals. These
      results demonstrate an important role of PKCI/HINT1 in modulating the behavioral
      response to AMPH. Furthermore, they indicate that the absence of this protein may
      be associated with dysregulation of postsynaptic DA transmission.

PMID- 17203013
TI  - A D2 antagonist enhances the rewarding and priming effects of a gambling episode
      in pathological gamblers.
AB  - Previous research indicated shared neurochemical substrates for gambling and
      psychostimulant reward. This suggests that dopamine substrates may directly
      govern the reinforcement process in pathological gambling. To investigate this
      issue, the present study assessed the effects of the relatively selective
      dopamine D2 antagonist, haloperidol (3 mg, oral) on responses to actual gambling
      (15 min on a slot machine) in 20 non-comorbid pathological gamblers and 18 non
      gambler controls in a placebo-controlled, double-blind, counterbalanced design.
      In gamblers, haloperidol significantly increased self-reported rewarding effects
      of gambling, post-game priming of desire to gamble, facilitation of reading speed
      to Gambling words, and gambling-induced elevation in blood pressure. In controls,
      haloperidol augmented gambling-induced elevation in blood pressure, but had no
      effect on other indices. The findings provide direct experimental evidence that
      the D2 substrate modulates gambling reinforcement in pathological gamblers.

PMID- 17203014
TI  - Endogenous serotonin excites striatal cholinergic interneurons via the activation
      of 5-HT 2C, 5-HT6, and 5-HT7 serotonin receptors: implications for extrapyramidal
      side effects of serotonin reuptake inhibitors.
AB  - The striatum is richly innervated by serotonergic afferents from the raphe
      nucleus. We explored the effects of this input on striatal cholinergic
      interneurons from rat brain slices, by means of both conventional intracellular
      and whole-cell patch-clamp recordings. Bath-applied serotonin (5-HT, 3-300
      microM), induced a dose-dependent membrane depolarization and increased the rate
      of spiking. This effect was mimicked by the 5-HT reuptake blockers citalopram and
      fluvoxamine. In voltage-clamped neurons, 5-HT induced an inward current, whose
      reversal potential was close to the K(+) equilibrium potential. Accordingly, the
      involvement of K(+) channels was confirmed either by increasing extracellular
      K(+) concentration and by blockade of K(+) channels with barium. Single-cell
      reverse transcriptase-polymerase chain reaction (RT-PCR) profiling demonstrated
      the presence of 5-HT2C, 5-HT6, and 5-HT7 receptor mRNAs in identified cholinergic
      interneurons. The depolarization/inward current induced by 5-HT was partially
      mimicked by the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodoamphetamine and
      antagonized by both ketanserin and the selective 5-HT2C antagonist RS102221,
      whereas the selective 5-HT3 and 5-HT4 receptor antagonists tropisetron and
      RS23597-190 had no effect. The depolarizing response to 5-HT was also reduced by
      the selective 5-HT6 and 5-HT7 receptor antagonists SB258585 and SB269970,
      respectively, and mimicked by the 5-HT7 agonist, 5-CT. Accordingly, activation of
      either 5-HT6 or 5-HT7 receptor induced an inward current. The 5-HT response was
      attenuated by U73122, blocker of phospholipase C, and by SQ22,536, an inhibitor
      of adenylyl cyclase. These results suggest that 5-HT released by serotonergic
      fibers originating in the raphe nuclei has a potent excitatory effect on striatal
      cholinergic interneurons.

PMID- 17203015
TI  - Improvement of prefrontal brain function in endogenous psychoses under atypical
      antipsychotic treatment.
AB  - Typical and atypical antipsychotics are thought to exert their effects on
      different neurotransmitter pathways with specific action of atypical compounds on
      the prefrontal cortex, but studies directly investigating the effect of those
      drugs on neurophysiological measures of prefrontal brain function are sparse. We
      therefore investigated the influence of different antipsychotics on an
      electrophysiological marker of prefrontal brain function (NoGo anteriorization,
      NGA) and neuropsychological test scores. For this purpose, 38 patients with
      endogenous psychoses were investigated at the beginning of a stationary
      psychiatric treatment and at a 6-week-follow-up. Patients were treated with
      typical or atypical antipsychotics, or a combination of both. They underwent
      psychopathological diagnostic and neuropsychological testing, as well as
      electrophysiological investigations during a Continuous Performance Test. The
      results indicate that typical and atypical antipsychotics differentially affected
      the development of the NGA over the course of the treatment, typical
      antipsychotics tending to result in decreased values at follow-up, and atypical
      antipsychotics stabilizing, or increasing this parameter. Performance in tests of
      frontal lobe function generally declined under typical antipsychotics and
      improved with atypical compounds, changes in Stroop interference correlated with
      changes in the NGA. We conclude that typical and atypical antipsychotics differ
      regarding their effect on prefrontal brain function in schizophrenia, atypical
      neuroleptics often showing a more favorable impact than conventional
      antipsychotics on respective parameters.

PMID- 17203016
TI  - Serial vagus nerve stimulation functional MRI in treatment-resistant depression.
AB  - Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open
      acute and long-term studies of treatment-resistant major depression. Mechanisms
      of action are not fully understood, although clinical data suggest slower onset
      therapeutic benefit than conventional psychotropic interventions. We set out to
      map brain systems activated by VNS and to identify serial brain functional
      correlates of antidepressant treatment and symptomatic response. Nine adults,
      satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed
      type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and
      enrolled in a 3-month, double-blind, placebo-controlled, serial-interleaved
      VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple
      regression mixed model with blood oxygenation level dependent (BOLD) signal as
      the dependent variable revealed that over time, VNS therapy was associated with
      ventro-medial prefrontal cortex deactivation. Controlling for other variables,
      acute VNS produced greater right insula activation among the participants with a
      greater degree of depression. These results suggest that similar to other
      antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal
      cortex correlates with the antidepressant response to VNS therapy. The increased
      acute VNS insula effects among actively depressed participants may also account
      for the lower dosing observed in VNS clinical trials of depression compared with
      epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and
      further clarify the regional neurobiological effects of VNS.

PMID- 17203017
TI  - Augmentation of SSRI effects on serotonin by 5-HT2C antagonists: mechanistic
      studies.
AB  - The treatment of depression may be improved by using an augmentation approach
      involving selective serotonin reuptake inhibitors (SSRIs) in combination with
      compounds that focus on antagonism of inhibitory serotonin receptors. Using
      microdialysis coupled to HPLC, it has recently been shown that the systemic co
      administration of 5-HT(2C) antagonists with SSRIs augmented the acute effect of
      SSRIs on extracellular 5-HT. In this paper, we have investigated the mechanism
      through which this augmentation occurs. The increase in extracellular 5-HT was
      not observed when both compounds were locally infused. However, varying the route
      of administration for both compounds differentially revealed that an augmentation
      took place when the 5-HT(2C) antagonist was locally infused into ventral
      hippocampus and the SSRI given systemically, but not when systemic 5-HT(2C)
      antagonist was co-administered with the local infusion of citalopram. This
      suggests that the release of extracellular serotonin in ventral hippocampus may
      be controlled by (an)other brain area(s). As 5-HT(2C) receptors are not
      considered to be autoreceptors, this would implicate that other neurotransmitter
      systems are involved in this process. To investigate which neurotransmitter
      systems were involved in the interaction, systemic citalopram was challenged with
      several glutamatergic, GABA-ergic, noradrenergic, and dopaminergic compounds to
      determine their effects on serotonin release in ventral hippocampus. It was
      determined that the involvement of glutamate, norepinephrine, and dopamine in the
      augmentation did not seem likely, whereas evidence implicated a role for the GABA
      ergic system in the augmentation.

PMID- 17203018
TI  - Amygdala-prefrontal disconnection in borderline personality disorder.
AB  - Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a
      core symptom of borderline personality disorder (BPD). We examined relative
      glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine)
      with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26
      impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala
      were visually traced on MRI scans co-registered to PET scans; rGMR was obtained
      for ventral and dorsal regions of the amygdala and Brodmann areas within the
      prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR
      for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and
      rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo:
      Controls showed significant positive correlations between right orbitofrontal
      (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak
      correlations between amygdala and the anterior PFC, with no distinction between
      dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls
      showed positive correlations between OFC and amygdala regions, whereas patients
      showed positive correlations between dorsolateral PFC and amygdala. Group
      differences between interregional correlational matrices were highly significant.
      Amygdala volume/metabolism: No group differences were found for amygdala volume,
      or metabolism in the placebo condition or in response to meta-chloropiperazine (m
      CPP). We demonstrated a tight coupling of metabolic activity between right OFC
      and ventral amygdala in healthy subjects with dorsoventral differences in
      amygdala circuitry, not present in IED-BPD. We demonstrated no significant
      differences in amygdala volumes or metabolism between BPD patients and controls.

PMID- 17203019
TI  - Serum paraoxonase/arylesterase activities in phenylketonuric patients on diet.
AB  - AIM: To compare serum paraoxonase/arylesterase (PON-aryl) activities in
      phenylketonuric (PKU) patients with high and low phenylalanine (Phe) blood
      concentration. PATIENTS AND METHODS: Seventeen poorly controlled PKU children
      (off diet) underwent clinical and laboratory examinations before and after 30
      days adhering to their special diet (on diet), whereas controls (N=24) were
      examined once. Lipid, lipoprotein levels and paraoxonase (PON 1) activities were
      measured with the Bayer Advia 1650 Clinical Chemistry System. Apolipoprotein AI
      (Apo AI) levels were determined by the Dade Behring BN ProSpec nephelometer,
      whereas total antioxidant capacity (TAC), PON-aryl and Phe levels were measured
      spectrophotometrically. RESULTS: Phe significantly differed among the groups.
      Lipids and lipoproteins, except high-density-lipoprotein-cholesterol (HDL-C) and
      Apo AI, were higher when off diet than those on diet. HDL-C and Apo AI were
      similar in patients and controls. TAC (0.99+/-0.19 mmol/l) was significantly
      lower when the patients were off diet than when they adhered to diet and controls
      (1.71+/-0.20 and 1.81+/-0.20 mmol/l P<0.001 respectively). PON 1 and PON-aryl
      activities (68+/-2 U/min/ml, 88+/-26 KU (min/ml) in children with high Phe were
      reduced as compared with those with low blood Phe levels (152+/-41 U/min/ml,
      107+/-23 KU/min/ml P<0.001) and controls (146+/-43 U/min/ml, 109+/-41 KU/min/ml
      P<0.001). The enzyme activities positively correlated with HDL-C and Apo AI when
      PKU patients were on diet and controls as well as with TAC in all the groups,
      whereas negatively correlated with Phe levels. CONCLUSIONS: PON-aryl activities
      are strongly related to the dietary control of PKU patients.

PMID- 17203021
TI  - Neurophysiology: Hodgkin and Huxley model--still standing?
AB  - Action potentials in cortical neurons show a variable threshold and a sudden rise
      in membrane potential at initiation. Naundorf et al. fail to explain these
      features using single- or double-compartment Hodgkin-Huxley-style models,
      suggesting instead that they could arise from cooperative opening of Na+
      channels, although there is no direct biological evidence to support this. Here
      we show that these so-called unique features are to be expected from Hodgkin
      Huxley models if the spatial geometry and spike initiation properties of cortical
      neurons are taken into account--it is therefore unnecessary to invoke exotic
      channel-gating properties as an explanation.

PMID- 17203026
TI  - Avoiding a chimaera quagmire.

PMID- 17203028
TI  - Libya and human values.

PMID- 17203029
TI  - Europe condemns Libyan trial verdict.

PMID- 17203030
TI  - European funding targets big biology.

PMID- 17203031
TI  - The dark side of E. coli.

PMID- 17203032
TI  - Open-access journal will publish first, judge later.

PMID- 17203033
TI  - Special report: alien Earth.

PMID- 17203035
TI  - When the party's over.

PMID- 17203036
TI  - Energy: that's oil, folks...

PMID- 17203037
TI  - Social sciences: life's a game.

PMID- 17203038
TI  - Pollution analysis flawed by statistical model.

PMID- 17203039
TI  - Advances in biology reveal truth about prokaryotes.

PMID- 17203040
TI  - RIKEN aids international structural genomics efforts.

PMID- 17203045
TI  - Constructive memory: the ghosts of past and future.

PMID- 17203046
TI  - Planetary science: Titan's lost seas found.

PMID- 17203047
TI  - Neurobiology: scent secrets of insects.

PMID- 17203048
TI  - Bioorganic chemistry: a sweet synthesis.

PMID- 17203050
TI  - Developmental biology: this worm is not for turning.

PMID- 17203051
TI  - Materials science: alloys go with the grain.

PMID- 17203052
TI  - Neurobiology: hit and miss.

PMID- 17203053
TI  - Cosmology: ripples of early starlight.

PMID- 17203054
TI  - Light in tiny holes.
AB  - The presence of tiny holes in an opaque metal film, with sizes smaller than the
      wavelength of incident light, leads to a wide variety of unexpected optical
      properties such as strongly enhanced transmission of light through the holes and
      wavelength filtering. These intriguing effects are now known to be due to the
      interaction of the light with electronic resonances in the surface of the metal
      film, and they can be controlled by adjusting the size and geometry of the holes.
      This knowledge is opening up exciting new opportunities in applications ranging
      from subwavelength optics and optoelectronics to chemical sensing and biophysics.

PMID- 17203055
TI  - Pulsar spins from an instability in the accretion shock of supernovae.
AB  - Rotation-powered radio pulsars are born with inferred initial rotation periods of
      order 300 ms (some as short as 20 ms) in core-collapse supernovae. In the
      traditional picture, this fast rotation is the result of conservation of angular
      momentum during the collapse of a rotating stellar core. This leads to the
      inevitable conclusion that pulsar spin is directly correlated with the rotation
      of the progenitor star. So far, however, stellar theory has not been able to
      explain the distribution of pulsar spins, suggesting that the birth rotation is
      either too slow or too fast. Here we report a robust instability of the stalled
      accretion shock in core-collapse supernovae that is able to generate a strong
      rotational flow in the vicinity of the accreting proto-neutron star. Sufficient
      angular momentum is deposited on the proto-neutron star to generate a final spin
      period consistent with observations, even beginning with spherically symmetrical
      initial conditions. This provides a new mechanism for the generation of neutron
      star spin and weakens, if not breaks, the assumed correlation between the
      rotational periods of supernova progenitor cores and pulsar spin.

PMID- 17203056
TI  - The lakes of Titan.
AB  - The surface of Saturn's haze-shrouded moon Titan has long been proposed to have
      oceans or lakes, on the basis of the stability of liquid methane at the surface.
      Initial visible and radar imaging failed to find any evidence of an ocean,
      although abundant evidence was found that flowing liquids have existed on the
      surface. Here we provide definitive evidence for the presence of lakes on the
      surface of Titan, obtained during the Cassini Radar flyby of Titan on 22 July
      2006 (T16). The radar imaging polewards of 70 degrees north shows more than 75
      circular to irregular radar-dark patches, in a region where liquid methane and
      ethane are expected to be abundant and stable on the surface. The radar-dark
      patches are interpreted as lakes on the basis of their very low radar
      reflectivity and morphological similarities to lakes, including associated
      channels and location in topographic depressions. Some of the lakes do not
      completely fill the depressions in which they lie, and apparently dry depressions
      are present. We interpret this to indicate that lakes are present in a number of
      states, including partly dry and liquid-filled. These northern-hemisphere lakes
      constitute the strongest evidence yet that a condensable-liquid hydrological
      cycle is active in Titan's surface and atmosphere, in which the lakes are filled
      through rainfall and/or intersection with the subsurface 'liquid methane' table.

PMID- 17203057
TI  - High-speed linear optics quantum computing using active feed-forward.
AB  - As information carriers in quantum computing, photonic qubits have the advantage
      of undergoing negligible decoherence. However, the absence of any significant
      photon-photon interaction is problematic for the realization of non-trivial two
      qubit gates. One solution is to introduce an effective nonlinearity by
      measurements resulting in probabilistic gate operations. In one-way quantum
      computation, the random quantum measurement error can be overcome by applying a
      feed-forward technique, such that the future measurement basis depends on earlier
      measurement results. This technique is crucial for achieving deterministic
      quantum computation once a cluster state (the highly entangled multiparticle
      state on which one-way quantum computation is based) is prepared. Here we realize
      a concatenated scheme of measurement and active feed-forward in a one-way quantum
      computing experiment. We demonstrate that, for a perfect cluster state and no
      photon loss, our quantum computation scheme would operate with good fidelity and
      that our feed-forward components function with very high speed and low error for
      detected photons. With present technology, the individual computational step (in
      our case the individual feed-forward cycle) can be operated in less than 150 ns
      using electro-optical modulators. This is an important result for the future
      development of one-way quantum computers, whose large-scale implementation will
      depend on advances in the production and detection of the required highly
      entangled cluster states.

PMID- 17203058
TI  - Dilatant shear bands in solidifying metals.
AB  - Compacted granular materials expand in response to shear, and can exhibit
      different behaviour from that of the solids, liquids and gases of which they are
      composed. Application of the physics of granular materials has increased the
      understanding of avalanches, geological faults, flow in hoppers and silos, and
      soil mechanics. During the equiaxed solidification of metallic alloys, there
      exists a range of solid fractions where the microstructure consists of a
      geometrically crowded disordered assembly of crystals saturated with liquid. It
      is therefore natural to ask if such a microstructure deforms as a granular
      material and what relevance this might have to solidification processing. Here we
      show that partially solidified alloys can exhibit the characteristics of a
      cohesionless granular material, including Reynolds' dilatancy and strain
      localization in dilatant shear bands 7-18 mean crystals wide. We show that this
      behaviour is important in defect formation during high pressure die casting of Al
      and Mg alloys, a global industry that contributes over $7.3 billion to the USA's
      economy alone and is used in the manufacture of products that include mobile
      phone covers and steering wheels. More broadly, these findings highlight the
      potential to apply the principles and modelling approaches developed in granular
      mechanics to the field of solidification processing, and also indicate the
      possible benefits that might be gained from exploring and exploiting further
      synergies between these fields.

PMID- 17203059
TI  - Influence of the intertropical convergence zone on the East Asian monsoon.
AB  - The Asian-Australian monsoon is an important component of the Earth's climate
      system that influences the societal and economic activity of roughly half the
      world's population. The past strength of the rain-bearing East Asian summer
      monsoon can be reconstructed with archives such as cave deposits, but the winter
      monsoon has no such signature in the hydrological cycle and has thus proved
      difficult to reconstruct. Here we present high-resolution records of the magnetic
      properties and the titanium content of the sediments of Lake Huguang Maar in
      coastal southeast China over the past 16,000 years, which we use as proxies for
      the strength of the winter monsoon winds. We find evidence for stronger winter
      monsoon winds before the Bolling-Allerod warming, during the Younger Dryas
      episode and during the middle and late Holocene, when cave stalagmites suggest
      weaker summer monsoons. We conclude that this anticorrelation is best explained
      by migrations in the intertropical convergence zone. Similar migrations of the
      intertropical convergence zone have been observed in Central America for the
      period ad 700 to 900 (refs 4-6), suggesting global climatic changes at that time.
      From the coincidence in timing, we suggest that these migrations in the tropical
      rain belt could have contributed to the declines of both the Tang dynasty in
      China and the Classic Maya in Central America.

PMID- 17203060
TI  - Direct estimation of per nucleotide and genomic deleterious mutation rates in
      Drosophila.
AB  - Spontaneous mutations are the source of genetic variation required for
      evolutionary change, and are therefore important for many aspects of evolutionary
      biology. For example, the divergence between taxa at neutrally evolving sites in
      the genome is proportional to the per nucleotide mutation rate, u (ref. 1), and
      this can be used to date speciation events by assuming a molecular clock. The
      overall rate of occurrence of deleterious mutations in the genome each generation
      (U) appears in theories of nucleotide divergence and polymorphism, the evolution
      of sex and recombination, and the evolutionary consequences of inbreeding.
      However, estimates of U based on changes in allozymes or DNA sequences and
      fitness traits are discordant. Here we directly estimate u in Drosophila
      melanogaster by scanning 20 million bases of DNA from three sets of mutation
      accumulation lines by using denaturing high-performance liquid chromatography.
      From 37 mutation events that we detected, we obtained a mean estimate for u of
      8.4 x 10(-9) per generation. Moreover, we detected significant heterogeneity in u
      among the three mutation-accumulation-line genotypes. By multiplying u by an
      estimate of the fraction of mutations that are deleterious in natural populations
      of Drosophila, we estimate that U is 1.2 per diploid genome. This high rate
      suggests that selection against deleterious mutations may have a key role in
      explaining patterns of genetic variation in the genome, and help to maintain
      recombination and sexual reproduction.

PMID- 17203062
TI  - A black hole in a globular cluster.
AB  - Globular star clusters contain thousands to millions of old stars packed within a
      region only tens of light years across. Their high stellar densities make it very
      probable that their member stars will interact or collide. There has accordingly
      been considerable debate about whether black holes should exist in these star
      clusters. Some theoretical work suggests that dynamical processes in the densest
      inner regions of globular clusters may lead to the formation of black holes of
      approximately 1,000 solar masses. Other numerical simulations instead predict
      that stellar interactions will eject most or all of the black holes that form in
      globular clusters. Here we report the X-ray signature of an accreting black hole
      in a globular cluster associated with the giant elliptical galaxy NGC 4472 (in
      the Virgo cluster). This object has an X-ray luminosity of about 4 x 10(39) erg
      s(-1), which rules out any object other than a black hole in such an old stellar
      population. The X-ray luminosity varies by a factor of seven in a few hours,
      which excludes the possibility that the object is several neutron stars
      superposed.

PMID- 17203061
TI  - The cellular machinery of Ferroplasma acidiphilum is iron-protein-dominated.
AB  - Ferroplasma is a genus of the Archaea, one of the three branches of the tree of
      life, and belongs to the order Thermoplasmatales (Euryarchaeota), which contains
      the most acidophilic microbes yet known. Ferroplasma species live in acid mine
      drainage, acidic pools and environments containing sulphidic ores such as pyrite
      and characterized by pH values of 0-2 and high concentrations of ferrous iron and
      other heavy metals. F. acidiphilum strain Y(T) is a chemoautotroph that grows
      optimally at pH 1.7 and gains energy by oxidizing ferrous iron and carbon by the
      fixation of carbon dioxide. Here we show that 86% of 189 investigated cellular
      proteins of F. acidiphilum are iron-metalloproteins. These include proteins with
      deduced structural, chaperone and catalytic roles, not described as iron
      metalloproteins in any other organism so far investigated. The iron atoms in the
      proteins seem to organize and stabilize their three-dimensional structures, to
      act as 'iron rivets'. Analysis of proteins of the phylogenetic neighbour
      Picrophilus torridus and of the habitat neighbour Acidithiobacillus ferrooxidans
      revealed far fewer and only typical metalloproteins. F. acidiphilum therefore has
      a currently unique iron-protein-dominated cellular machinery and biochemical
      phylogeny.

PMID- 17203063
TI  - Looking ahead with structural genomics.
AB  - Structural genomics initiatives aim to create a library of all existing protein
      folds. We take a look at the progress that has been made and what more needs to
      be done.

PMID- 17203065
TI  - Structural proteomics: from the molecule to the system.
AB  - Over the next few years, structural proteomics will grapple with the problem of
      visualizing increasingly elaborate structures, from the atomic details of protein
      structures up to subcellular structures and the whole cell. A recent EU workshop
      addressed the question of what experimental and theoretical approaches,
      technologies and infrastructures this will demand.

PMID- 17203066
TI  - Wrong PH for RNA degradation.

PMID- 17203067
TI  - Insights into DNA deaminases.

PMID- 17203068
TI  - Botulinum neurotoxin B-host receptor recognition: it takes two receptors to
      tango.

PMID- 17203069
TI  - A Hec of a microtubule attachment.

PMID- 17203070
TI  - All mixed up.

PMID- 17203073
TI  - aPKC-mediated phosphorylation regulates asymmetric membrane localization of the
      cell fate determinant Numb.
AB  - In Drosophila, the partition defective (Par) complex containing Par3, Par6 and
      atypical protein kinase C (aPKC) directs the polarized distribution and unequal
      segregation of the cell fate determinant Numb during asymmetric cell divisions.
      Unequal segregation of mammalian Numb has also been observed, but the factors
      involved are unknown. Here, we identify in vivo phosphorylation sites of
      mammalian Numb and show that both mammalian and Drosophila Numb interact with,
      and are substrates for aPKC in vitro. A form of mammalian Numb lacking two
      protein kinase C (PKC) phosphorylation sites (Numb2A) accumulates at the cell
      membrane and is refractory to PKC activation. In epithelial cells, mammalian Numb
      localizes to the basolateral membrane and is excluded from the apical domain,
      which accumulates aPKC. In contrast, Numb2A is distributed uniformly around the
      cell cortex. Mutational analysis of conserved aPKC phosphorylation sites in
      Drosophila Numb suggests that phosphorylation contributes to asymmetric
      localization of Numb, opposite to aPKC in dividing sensory organ precursor cells.
      These results suggest a model in which phosphorylation of Numb by aPKC regulates
      its polarized distribution in epithelial cells as well as during asymmetric cell
      divisions.

PMID- 17203072
TI  - Caenorhabditis elegans SAND-1 is essential for RAB-7 function in endosomal
      traffic.
AB  - The small rab-GTPase RAB-7 acts in endosome and endosome to lysosome traffic. We
      identified SAND-1 as a protein required for RAB-7 function based on similarities
      between SAND-1 and RAB-7 RNAi phenotypes. Although the initial uptake of yolk
      protein in oocytes, or of soluble secreted (ss) GFP in coelomocytes, appeared
      normal, further transport along the endocytic traffic route was delayed in the
      absence of SAND-1 function, and yolk proteins failed to reach yolk granules
      efficiently. Moreover, in coelomocytes, ssGFP and BSA-Texas-Red were endocytosed
      but not transported to lysosomes. We show that SAND-1 is essential for RAB-7
      function at the transition from early to late endosomes, but not for RAB-7
      function at lysosomes.

PMID- 17203074
TI  - Cex1p is a novel cytoplasmic component of the Saccharomyces cerevisiae nuclear
      tRNA export machinery.
AB  - The Saccharomyces cerevisiae Yor112wp, which we named Cex1p, was identified using
      a yeast tRNA three-hybrid interaction approach and an in vivo nuclear tRNA export
      assay as a cytoplasmic component of the nuclear tRNA export machinery. Cex1p
      binds tRNA saturably, and associates with the nuclear pore complex by interacting
      directly with Nup116p. Cex1p co-purifies with the nuclear tRNA export receptors
      Los1p and Msn5p, the eukaryotic elongation factor eEF-1A, which delivers
      aminoacylated tRNAs to the ribosome, and the RanGTPase Gsp1p, but not with Cca1p,
      a tRNA maturation enzyme that facilitates translocation of non-aminoacylated
      tRNAs across the nuclear pore complex. Depletion of Cex1p and eEF-1A or Los1p
      significantly reduced the efficiency of nuclear tRNA export. Cex1p interacts with
      Los1p but not with eEF-1A in vitro. These findings suggest that Cex1p is a
      component of the nuclear aminoacylation-dependent tRNA export pathway in S.
      cerevisiae. They also suggest that Cex1p collects aminoacyl-tRNAs from the
      nuclear export receptors at the cytoplasmic side of the nuclear pore complex, and
      transfers them to eEF-1A using a channelling mechanism.

PMID- 17203075
TI  - Structure of GlnK1 with bound effectors indicates regulatory mechanism for
      ammonia uptake.
AB  - A binary complex of the ammonia channel Amt1 from Methanococcus jannaschii and
      its cognate P(II) signalling protein GlnK1 has been produced and characterized.
      Complex formation is prevented specifically by the effector molecules Mg-ATP and
      2-ketoglutarate. Single-particle electron microscopy of the complex shows that
      GlnK1 binds on the cytoplasmic side of Amt1. Three high-resolution X-ray
      structures of GlnK1 indicate that the functionally important T-loop has an
      extended, flexible conformation in the absence of Mg-ATP, but assumes a compact,
      tightly folded conformation upon Mg-ATP binding, which in turn creates a 2
      ketoglutarate-binding site. We propose a regulatory mechanism by which nitrogen
      uptake is controlled by the binding of both effector molecules to GlnK1. At
      normal effector levels, a 2-ketoglutarate molecule binding at the apex of the
      compact T-loop would prevent complex formation, ensuring uninhibited ammonia
      uptake. At low levels of Mg-ATP, the extended loops would seal the ammonia
      channels in the complex. Binding of both effector molecules to P(II) signalling
      proteins may thus represent an effective feedback mechanism for regulating
      ammonium uptake through the membrane.

PMID- 17203077
TI  - Fragile egos.

PMID- 17203076
TI  - Nutrient starvation promotes condensin loading to maintain rDNA stability.
AB  - Nutrient starvation or rapamycin treatment, through inhibition of target of
      rapamycin, causes condensation of ribosomal DNA (rDNA) array and nucleolar
      contraction in budding yeast. Here we report that under such conditions,
      condensin is rapidly relocated into the nucleolus and loaded to rDNA tandem
      repeats, which is required for rDNA condensation. Rpd3-dependent histone
      deacetylation is necessary and sufficient for condensin's relocalization and
      loading to rDNA array, suggesting that histone modification plays a regulatory
      role for condensin targeting. Rapamycin independently, yet coordinately, inhibits
      rDNA transcription and promotes condensin loading to rDNA array. Unexpectedly, we
      found that inhibition of rDNA transcription in the absence of condensin loading
      leads to rDNA instability. Our data suggest that enrichment of condensin prevents
      rDNA instability during nutrient starvation. Together, these observations unravel
      a novel role for condensin in the maintenance of regional genomic stability.

PMID- 17203078
TI  - Is there a link between diet and esophageal cancer?

PMID- 17203079
TI  - How effective are oral hyoscine butylbromide and paracetamol for the relief of
      crampy abdominal pain?

PMID- 17203080
TI  - Is re-treatment with peginterferon alpha-2a and ribavirin effective in patients
      with relapsed chronic hepatitis C?

PMID- 17203081
TI  - What is the optimal laparoscopic antireflux procedure for children with
      gastroesophageal reflux disease?

PMID- 17203082
TI  - Should intraoperative cholangiography be routinely attempted during laparoscopic
      cholecystectomy?

PMID- 17203083
TI  - Is there an optimal surgical treatment for infants with perforated necrotizing
      enterocolitis?

PMID- 17203084
TI  - Is ERCP necessary in all patients with an abnormal intraoperative cholangiogram?

PMID- 17203085
TI  - How should hepatitis C be managed in patients aged 65 years and older?

PMID- 17203086
TI  - Management strategies in alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) and its complications is still one of the most
      frequent causes of death in the Western world. Treatment modalities for both
      alcoholic steatohepatitis (ASH; the major inflammatory complication of ALD) and
      alcoholic liver cirrhosis are insufficient. Severe ASH is associated with a high
      mortality; although glucocorticoid treatment has been reported to improve
      survival, meta-analyses of clinical trials performed to date have failed to show
      a convincing benefit of such an approach. Most of the progress in understanding
      these diseases, especially ASH, has come from studies of cytokines. Various
      proinflammatory cytokines, such as tumor necrosis factor (TNF), have been
      proposed to have an important role in the pathophysiology of ALD and its
      complications. Pilot studies on the use of anti-TNF drugs, such as pentoxifylline
      or infliximab, in the treatment of ASH have now been performed with various
      levels of success. The treatment of patients with alcohol-related cirrhosis is
      mainly symptomatic and no therapies are currently available except orthotopic
      liver transplantation for end-stage liver disease. Independent of the stage of
      disease, abstinence from alcohol is the cornerstone of management. New treatment
      modalities for these diseases are eagerly awaited.

PMID- 17203087
TI  - How to manage the difficult-to-treat dyspeptic patient.
AB  - The main causes of dyspepsia are unexplained gastroduodenal symptoms (i.e.
      functional dyspepsia), peptic ulcer disease, reflux disease and, rarely,
      malignancy. A careful clinical evaluation and upper endoscopy will exclude most
      of the major causes of dyspepsia. The absence of alarm features is reassuring.
      The yield of other diagnostic tests in this clinical situation is low, and repeat
      endoscopy is unlikely to be cost-effective. By definition, the difficult-to-treat
      patient with functional dyspepsia has already had Helicobacter pylori infection
      excluded or eradicated, has failed to respond to an adequate trial of acid
      suppression therapy that used appropriate doses and, therefore, seeks other
      solutions. It is likely that patients who have failed to respond to previous
      trials of a PPI will not experience therapeutic gains with high-dose PPI therapy.
      A major gastroduodenal motor disorder should be suspected if there is severe
      early satiation (inability to finish a normal-sized meal), postprandial fullness,
      or persistent nausea and vomiting; here, an assessment of gastric emptying or
      gastric accommodation can be considered, to tailor therapy. Antidepressants
      (especially low-dose tricyclic agents) and psychological therapies can be useful.
      Creation of a logical management plan that includes patient education and support
      remains key.

PMID- 17203088
TI  - Drug insight: the role of albumin in the management of chronic liver disease.
AB  - Albumin is the most abundant protein in the circulation. Its main physiologic
      function is to maintain colloid osmotic pressure. Better understanding of
      albumin's other physiologic functions has expanded its application beyond
      maintenance of intravascular volume. In patients with cirrhosis, albumin has been
      used as an adjunct to diuretics to improve the diuretic response. It has also
      been used to prevent circulatory dysfunction developing after large-volume
      paracentesis. Newer indications in cirrhotic patients include preventing
      hepatorenal syndrome in those with spontaneous bacterial peritonitis, and
      treating established hepatorenal syndrome in conjunction with vasoconstrictor
      therapies. The use of albumin for many of these indications is controversial,
      mostly because of the paucity of well-designed, randomized, controlled trials.
      The cost of albumin infusions, lack of clear-cut benefits for survival, and fear
      of transmitting unknown viruses add to the controversy. The latest indication for
      albumin use in cirrhotic patients is extracorporeal albumin dialysis, which has
      shown promise for the treatment of hepatic encephalopathy; its role in
      hepatorenal syndrome or acute on chronic liver failure has not been established.
      Efforts should be made to define the indications for albumin use, dose of albumin
      required and predictors of response, so that patients gain the maximum benefit
      from its administration.

PMID- 17203089
TI  - Napoleon Bonaparte's gastric cancer: a clinicopathologic approach to staging,
      pathogenesis, and etiology.
AB  - BACKGROUND: Numerous hypotheses on the cause of Napoleon Bonaparte's death have
      been proposed, including hereditary gastric cancer, arsenic poisoning, and
      inappropriate medical treatment. We aimed to determine the etiology and
      pathogenesis of Napoleon's illness by a comparison of historical information with
      current clinicopathologic knowledge. INVESTIGATIONS: Evaluation of Napoleon's
      clinical history, original autopsy reports, and of historical documents. The
      clinicopathologic data from 135 gastric cancer patients were used for comparison
      with the data available on Napoleon. DIAGNOSIS: At least T3N1M0 (stage IIIA)
      gastric cancer. Napoleon's tumor extended from the cardia to the pylorus (>10 cm)
      without infiltration of adjacent structures, which provides strong evidence for
      at least stage T3. The N1 stage was determined by the presence of several
      enlarged and hardened regional (perigastric) lymph nodes, and the M0 stage by the
      absence of distant metastasis. Analysis of the available historical documents
      indicates that Napoleon's main risk factor might have been Helicobacter pylori
      infection rather than a familial predisposition. CONCLUSIONS: Our analysis
      suggests that Napoleon's illness was a sporadic gastric carcinoma of advanced
      stage. Patients with such tumors have a notoriously poor prognosis.

PMID- 17203092
TI  - Fraud in our laboratories?

PMID- 17203093
TI  - Is 'cloning' mad, bad and dangerous?

PMID- 17203094
TI  - Fraud: causes and culprits as perceived by science and the media. Institutional
      changes, rather than individual motivations, encourage misconduct.

PMID- 17203095
TI  - Sharing benefits in international health research. Research-capacity building as
      an example of an indirect collective benefit.

PMID- 17203096
TI  - In vino scientia. Although science has much to offer winemakers, skill and
      experience will always prevail over technology.

PMID- 17203097
TI  - Is eternal youth scientifically plausible? Research on the role of free radicals
      in ageing gives cause for optimism.

PMID- 17203100
TI  - Xist and the order of silencing.
AB  - X inactivation is the mechanism by which mammals adjust the genetic imbalance
      that arises from the different numbers of gene-rich X-chromosomes between the
      sexes. The dosage difference between XX females and XY males is functionally
      equalized by silencing one of the two X chromosomes in females. This dosage
      compensation mechanism seems to have arisen concurrently with early mammalian
      evolution and is based on the long functional Xist RNA, which is unique to
      placental mammals. It is likely that previously existing mechanisms for other
      cellular functions have been recruited and adapted for the evolution of X
      inactivation. Here, we critically review our understanding of dosage compensation
      in placental mammals and place these findings in the context of other cellular
      processes that intersect with mammalian dosage compensation.

PMID- 17203101
TI  - Peptidyl-prolyl cis/trans isomerases and transcription: is there a twist in the
      tail?
AB  - Eukaryotic transcription is regulated predominantly by the post-translational
      modification of the participating components. One such modification is the cis
      trans isomerization of peptidyl-prolyl bonds, which results in a conformational
      change in the protein involved. Enzymes that carry out this reaction include the
      yeast peptidyl-prolyl cis/trans isomerase Ess1 and its human counterpart Pin1,
      both of which recognize phosphorylated target motifs exclusively. Consequently,
      they operate together with proline-directed serine-threonine kinases and
      phosphatases. High-profile client proteins involved in transcription include
      steroid hormone receptors, cell-cycle regulators and immune mediators. Other key
      targets are elements of the transcription machinery, including the multiply
      phosphorylated carboxy-terminal domain of RNA polymerase II. Changes in isomerase
      activity have been shown to alter the transactivation potential, protein
      stability or intracellular localization of these client proteins. The resulting
      disruption to developmental processes and cell proliferation has been linked, in
      some cases, to human cancers.

PMID- 17203102
TI  - A fruitfly's guide to keeping the brain wired.
AB  - The behaviour of all animals is governed by the connectivity of neural circuits
      in the brain. Neurodevelopmental and neurodegenerative diseases, as well as
      traumatic injuries to the nervous system, can alter or disrupt the normal
      connectivity of the brain and result in disability. In this review, we highlight
      the contributions of the genetic model organism Drosophila melanogaster to our
      understanding of neural connectivity in health and disease. In this context we
      also discuss the research areas in which we believe the fruitfly is likely to be
      a useful model system in the future.

PMID- 17203103
TI  - Is HIV-1 evolving to a less virulent form in humans?
AB  - During the rapid spread of HIV-1 in humans, the main (M) group of HIV-1 has
      evolved into ten distinct subtypes, undergone countless recombination events and
      diversified extensively. The impact of this extreme genetic diversity on the
      phenotype of HIV-1 has only recently become a research focus, but early findings
      indicate that the dominance of HIV-1 subtype C in the current epidemic might be
      related to the lower virulence of this subtype compared with other subtypes.
      Here, we explore whether HIV-1 has reached peak virulence or has already started
      the slow path to attenuation.

PMID- 17203105
TI  - Perimacular retinal folds and nonaccidental injury--yes, no, or maybe?

PMID- 17203107
TI  - Construction and characterization of efficient, stable and safe replication
      deficient foamy virus vectors.
AB  - As serious side effects affected recent virus-mediated gene transfer studies,
      novel vectors with improved safety profiles are urgently needed. In the present
      study, replication-deficient retroviral vectors based on feline foamy virus (FFV)
      were constructed and analyzed. The novel FFV vectors are devoid of almost the
      complete env gene plus the internal promoter - accessory bel gene cassette
      including the gene for the viral transcriptional transactivator Bel1/Tas. In
      these Bel1/Tas-independent vectors, expression of the lacZ (beta-galactosidase)
      marker gene is directed by the heterologous, constitutively active human
      ubiquitin C promoter (ubi). Env-transcomplemented vectors have un-concentrated
      titers of more than 10(5) transducing units/ml. The vectors allow efficient
      transduction of a broad array of diverse target cells, which can be increased by
      repeated vector exposure. However, the number of lacZ marker gene expressing
      cells decreased slightly upon serial passages of the transduced cells. Vectors
      carrying a self-inactivating (SIN) deletion of the TATA box and most parts of the
      viral promoter were not rescued by wt FFV whereas those with the intact or a
      partially deleted promoter were readily reactivated. This finding indicates that
      the viral promoters are in fact non-functional, pointing to a highly advantageous
      safety profile of these new FFV-ubi-lacZ-SIN vectors.

PMID- 17203106
TI  - Cotransduction of CCL27 gene can improve the efficacy and safety of IL-12 gene
      therapy for cancer.
AB  - Interleukin-12 (IL-12) is a potent antitumoral cytokine, but high doses are
      toxic. Herein, we demonstrate that combinational transduction of IL-12 and CC
      chemokine ligand-27 (CCL27) genes into pre-existing murine OV-HM ovarian
      carcinoma and Meth-A fibrosarcoma, by using RGD fiber-mutant adenoviral vectors,
      could induce tumor regression and relieve systemic side effects more effectively
      than either treatment alone. The antitumor activity of the IL-12 and CCL27
      combination treatment was T-cell-dependent, and development of long-term specific
      immunity was confirmed in rechallenge experiments. Immunohistochemical analysis
      of tumors transduced with CCL27 gene alone or cotransduced with IL-12 and CCL27
      genes showed significant increases in numbers of infiltrating CD3(+) T cells,
      which included both CD4(+) and CD8(+) cells. Additionally, cotransduction with IL
      12 and CCL27 genes could more efficiently activate tumor-infiltrating immune
      cells than transduction with CCL27 alone, as determined by the frequency of
      perforin-positive cells and expression levels of IFN-gamma. Furthermore, mice
      treated with the IL-12 and CCL27 combination compared with those treated with IL
      12 alone showed milder pathological changes, for example, lymphocyte infiltration
      and extramedullary hematopoiesis, in lung, liver and spleen. Our data provide
      evidence that combinational in vivo transduction with IL-12 and CCL27 genes is a
      promising approach for the development of cancer immunogene therapy that can
      simultaneously recruit and activate tumor-infiltrating immune cells.

PMID- 17203109
TI  - Immunopathogenesis of infectious disease: injury and death from friendly fire.

PMID- 17203111
TI  - Management of optic neuritis in a developing African country.
AB  - AIM: To show the value of sub-Tenon's depo-methylprednisolone acetate followed by
      oral prednisolone in the management of optic neuritis in African patients.
      METHODOLOGY: Two female patients who presented to the University of Benin
      Teaching Hospital, Benin city, Nigeria and one male patient who presented to the
      Eye clinic of the Nigerian National Petroleum Corporation, Warri, Nigeria with
      optic neuritis were given a single dose of sub-Tenon's depo-methylprednisolone
      acetate 40 mg followed by oral prednisolone 60 mg daily and their vision
      monitored. RESULTS: In all the 3 cases, there was rapid improvement in visual
      acuity from as low as ? light perception, counting fingers at 1 metre and at 4
      metre to 6/6 within 2-3 weeks with improvement in colour vision. After 3 years
      and 5 years follow-up in 2 cases, there was no recurrence of optic neuritis and
      no neurological deficit occurred. CONCLUSION: Sub-Tenon's depo-methylprednisolone
      acetate followed by oral prednisolone is a safe and effective alternative
      treatment for optic neuritis in black African patients.

PMID- 17203112
TI  - Alpha erythropoietin in the management of anaemia of prematurity: a report of
      three cases in Nigeria.
AB  - Anaemia of prematurity is a common problem encountered in most special care baby
      units warranting often repeated blood transfusions with its inherent dangers. We
      present three patients in Nigeria who were very low birth weight premature babies
      on whom recombinant erythropoietin was used as an efficient replacement for blood
      transfusions. All three patients showed a progressive drop in haemoglobin
      concentration from the first to the sixth to eight week of life with development
      of heamic murmurs and insignificant reticulocyte responses, and were planned for
      transfusion therapy. The parents of all the patients strongly refused transfusion
      therapy (one on religious grounds) warranting the use of recombinant
      erythropoietin to which there was a significant response in all three patients
      with elevation of haemoglobin concentration, PCV, and reticulocyte counts, and
      obviating the planned transfusions. No significant side effects were also
      noticed. We suggest further controlled trials to establish this mode of therapy.

PMID- 17203113
TI  - Conjunctival melanoma in a 55 year old male Nigerian: a case report.
AB  - BACKGROUND: Conjunctival melanoma is a rare occurrence in the Negroid race.
      PURPOSE: To report a case of a 55 year old security man with right conjunctival
      melanoma. METHOD: A 55 old man was operated on to remove a pigmented right bulbar
      conjuctival growth. The specimen was submitted to Lagos University Teaching
      Hospital Lagos and Harold Wood Hospital England for histopathologic examination
      and confirmation. RESULTS: Surgery was successful and histopathologic and
      immunohistochemical studies confirmed a diagnosis of a nodular malignant
      melanoma. CONCLUSION: The need for the provision of definitive investigative tool
      (immunohistochemical studies) to facilitate definitive diagnosis and management
      of such cases in some recognised centres in Nigeria cannot be overemphasised.

PMID- 17203114
TI  - An unusual faciocerebellar arrow injury: successful surgical removal in a peasant
      Nigerian: a case report.
AB  - INTRODUCTION: Reports of penetrating injuries of the cranium have been mainly
      craniocerebral or faciocerebral, craniocerebellar projectiles are few. CASE: We
      present a case of a 23 year old Nigerian with a craniofacial penetrating injury
      by a hunting arrow. The trajectory of the arrow through the facial skeleton
      across the craniocervical junction into the posterior fossa makes this unique in
      the literature. Successful operative retrieval by a joint team of neurosurgeons
      and otorhinolaryngologists, problems of delayed presentation and inadequate
      diagnostic facilities are highlighted. CONCLUSION: The morbidity-free outcome of
      surgical removal despite the delay in presentation and management in our practice
      setting with limited facilities are the salient points of this presentation.

PMID- 17203115
TI  - The effect of nifedipine on oral contraceptive-induced hypertension in rats.
AB  - OBJECTIVE: Administration of oral contraceptive (OC) steroids is associated with
      an increased risk of developing hypertension, although the mechanisms underlying
      this effect are not well established. This study therefore sought to investigate
      the effect of L-type calcium channel blocker, nifedipine on OC-induced
      hypertension. METHODS: Female Sprague-Dawley rats received OC
      (norgestrel/ethinyloestradiol) and/or nifedipine orally for 10 weeks. . Blood
      pressure and heart rate were thereafter recorded under anaesthesia from the
      femoral artery with a Grass Polygraph 7D model, whereas plasma and urinary Na+
      and K+ concentrations were measured using a flame photometer. The stable
      oxidation products of nitric oxide, urinary nitrite/nitrate (NO) were measured in
      urine by means of the brucine method. RESULTS: OC administration led to
      significant (p<0.05) increases in blood pressure and plasma Na+, and decreases in
      body weight, food and water consumption, excretion of Na+ and NO. Concomitant
      treatment with nifedipine significantly (p<0.05) abrogated the alterations
      induced by OC administration. CONCLUSION: This study provides evidence that the
      development of OC-induced hypertension is prevented by calcium channel blockade
      via improved renal handling of sodium and nitric oxide. The finding confirms the
      involvement of calcium channels in OC hypertension.

PMID- 17203117
TI  - Prevalence and determinants of erectile dysfunction among people with type 2
      diabetes in Ilorin, Nigeria.
AB  - STUDY OBJECTIVES: To determine the prevalence and determinants of Erectile
      Dysfunction (ED) among men with Type 2 diabetes mellitus. MATERIALS AND METHODS:
      Seventy-seven adult men with Type 2 Diabetes Mellitus were assessed for Erectile
      Dysfunction using the 'IIEF-5' questionnaire. They were also assessed for the
      presence of certain clinical factors in other to determine their degree of
      correlation with ED. RESULTS: The mean age of the study subjects was 56.8(+/-2.4)
      years. Almost all (96.1%) were married. Forty-four (56.4%) men volunteered a
      history of Erectile Dysfunction. When assessed with the 'IIEF - 5' questionnaire,
      the prevalence of any degree of ED was 74% while moderate to severe ED was found
      in 39(51%) of the patients. The only clinical variables that had statistically
      significant correlation with ED were the age of the patients (p=0.04) as well as
      the duration of diabetes (p=0.04). CONCLUSION: - Erectile Dysfunction is a very
      common condition among men with Type 2 Diabetes mellitus in Ilorin, Nigeria and
      should therefore be routinely sought for by the clinicians. The two clinical
      factors that confer significant risk to development of ED, from this study are
      non-modifiable. More emphasis should therefore be placed on treatment rather than
      the prevention of this condition.

PMID- 17203116
TI  - Interactions between sodium intake, calcium supplement, renal excretion and blood
      pressure in Sprague-Dawley rats.
AB  - INTRODUCTION: The mechanisms responsible for genesis of salt-induced hypertension
      and its prevention by dietary calcium supplementation are still not clear. Hence,
      the effect of salt (NaCl) and calcium supplement on blood pressure and renal
      excretion were investigated. METHODOLOGY: Daily food consumption, water, salt and
      calcium intake, as well as urine volume and pH were determined. At the end of the
      feeding period, animals were anaesthetised and the electrocardiographic and blood
      pressure measurements were done. RESULTS: Salt-loaded rats (SR) consumed more
      salt and water but less calcium, and excreted more urine and hydrogen ion than
      control rats (NR). There was elevation of mean arterial pressure (MAP) in SR
      (132.63 +/- 2.3 mmHg) compared with NR (94.00 +/- 2.2 mmHg) but there was no
      significant difference in their heart rates (HR) (395 +/- 11.7 vs. 429 +/- 15.4
      beats/min). However, salt-loaded-calcium-fed rats (SCaR) had similar MAP as NR
      (99.29 +/- 1.8 mmHg) and a lower HR (379 +/- 14.9 beats/min). A reduction in
      water consumption and an increase in urine output as well as urinary hydrogen ion
      were noted in SCaR compared with SR. Calcium alone (CaR) did not have any effect
      on MAP (88.01 +/- 1.3 mmHg) and HR (413 +/- 7.98 beats/min). There was no
      difference in the organ/body-weight ratios of the aortae among the experimental
      rats. However, there was renal hypertrophy in SR and SCaR. Also, the hearts of SR
      were bigger than CaR. The mean electrical axis of hearts showed a tendency
      towards left ventricular hypertrophy in SR, which was greater than SCaR.
      CONCLUSION: The results suggest that salt loading caused renal hypertrophy and a
      tendency towards left ventricular hypertrophy. There are associated salt and
      water retention resulting in alteration of some cardiovascular function. Dietary
      calcium supplementation reversed these functional defects.

PMID- 17203118
TI  - Knowledge of and attitude towards road traffic codes among commercial motorcycle
      riders in Anambra State.
AB  - Road traffic accidents (rtas) represent a major epidemic of non communicable
      disease in the country and has since escalated with the introduction of the new
      phenomenon of commercial motorcycle transportation such as is found in the two
      urban towns of nnewi and Awka of Anambra state, Nigeria. making use of a pre
      tested, semi structured, interviewer administered questionnaire, relevant data on
      socio demographic and motorcycle characteristics were collected from a sample of
      commercial motorcyclists selected by systematic sampling technique. their
      knowledge of and attitude towards road traffic and safety codes were elicited.
      The result showed that the all-male commercial motorcyclists had a mean age of
      30+8.9 years. one hundred and seventy six (32.6%) possessed good knowledge of
      road traffic codes and safety, while 35 (6.5%) exhibited good attitude towards
      them. both knowledge of and attitude towards traffic codes and safety improved
      with increase in educational level (p<0.005, p<0.001 respectively). the younger
      motorcyclists also possessed statistically significant better knowledge of
      traffic codes than their older counterparts (p<0.025). attitude to traffic codes
      and safety had no association with age of the motorcyclists (p>0.25). the study
      has provided useful information on the knowledge of and attitude towards road
      traffic and safety codes among commercial motorcyclists in nigeria. pursuit of
      knowledge through formal and informal education should run pari pasu with efforts
      to improve the nigerian economy in order to ensure a sustainable positive
      attitudinal change towards road traffic codes and safety among commercial
      motorcyclists.

PMID- 17203119
TI  - Pathology services delivery: policy analysis using a Nigerian tertiary
      institution as a prototype.
AB  - BACKGROUND: Laboratory services delivery face criticisms on daily basis by the
      patients (the beneficiary), the clinicians (the user), and the hospital
      management (the policy maker). The service provider (the laboratory) is faced
      with the task of trying to explain her problems. OBJECTIVE OF THE STUDY: Was to
      critically do a policy analysis of the problems of laboratory service delivery,
      with the aim of identifying the causes of these problems and making
      recommendations to the policy makers. SETTING: The University of Benin Teaching
      Hospital, a foremost tertiary institution in Nigeria. METHOD: George Kent's
      normative policy analysis model was used to analyse the laboratory guidelines and
      procedures of sample collection, transportation, analysis and eventual generation
      of laboratory results. All the steps in the guidelines are analysed using the
      fifteen steps in Kent's normative model of policy analysis. RESULTS: The policy
      analysis shows that problems of laboratory services delivery are triangular with
      the patient at the center of the triangle. The most important finding of this
      analysis is that there is no formal laboratory service policy to guide all the
      actors i.e. the hospital management, laboratory staff and the clinicians.
      Problems arising from the laboratory are solved through the use of circular
      letters, likened to administrative incremental model of decision-making.
      CONCLUSION: There is a need to have a formal policy. A formal policy on
      laboratory service delivery will guide the provider, the user and the policy
      makers in solving the problems that originate from the laboratory service on a
      permanent basis. It will also establish a regular method of evaluating the
      services that are provided by the laboratory.

PMID- 17203120
TI  - Medical students perception of undergraduate ophthalmology training in Nnamdi
      Azikiwe University Nnewi Campus.
AB  - AIM: To determine the perception and aspiration of medical students towards
      ophthalmology. METHOD: Information for the study was obtained through forced
      choice questionnaire set to 102 medical students in 2000/2001 graduating class in
      Nnamdi Azikiwe University. RESULTS: One hundred questionnaires were completed. As
      a specialty of choice ophthalmology ranked fourth {16.0%} as a first choice;
      second {21.0%} as a second choice and first {26.0%} as a third choice. Ninety
      five of respondents found ophthalmology training useful. CONCLUSION: This cohort
      of medical students considered ophthalmic training in this institution essential
      and adequate. Undergraduate ophthalmic course should ensure an understanding of
      the basic principles of ophthalmology and should be designed to motivate the
      interest and confidence of the medical students in the specialty. Training period
      should be at least 4 weeks. With appropriate training ophthalmology can attract
      reasonable interest as a choice for specification.

PMID- 17203121
TI  - Exclusive breastfeeding frequency during the first seven days of life in term
      neonates.
AB  - SUMMARY The study evaluated the effect of frequent suckling on neonatal serum
      bilirubin level, weight gain and passage of meconium in exclusively breastfed
      (Ebfed) neonates in the first week of lactation. These variables were
      investigated for 358 healthy full-term, EBfed Nigerian newborn, delivered
      vaginally without complications at the Jos University Teaching Hospital (JUTH) in
      their first week of life. Their maternal breast problems and time of achievement
      of let-down reflex were also evaluated. Mothers nursed their newborns on the
      average of 13.3 + 1.6 times in the first 24 hours. This non-significantly
      decreased to 13.1 + 1.2 by the 7th day. Significant positive correlations were
      found between the frequency of EBfing and passage of meconium in the first 24
      hours of life ( r = 0.41, p < 0.05), and weight gain by day 7 ( r = 0.34,
      p<0.001). Inverse relationship was observed between frequency of suckling and
      neonatal serum bilirubin level on days 3 and 7 (r = -.13 and -.15), time of
      achievement of maternal let-down reflex ( r = -.43) and their breast problems (r
      = -.38), P values < 0.05. We therefore concluded that frequent suckling during
      EBfing has beneficial health effect on both the mother and her newborn in the
      first week of lactation. BG.

PMID- 17203122
TI  - Comparison of suxamethonium and priming with atracurium for rapid sequence
      orotracheal intubation in a Nigerian adult population.
AB  - OBJECTIVE: To compare suxamethonium with atracurium using the priming principle,
      for rapid sequence orotracheal intubation assessing onset time, time to
      successful laryngoscopy and intubation and quality of intubating conditions.
      PATIENTS AND METHODS: A prospective double-blind, randomised study was performed
      in 90 ASA physical status I and II patients aged between 18 and 64 years
      undergoing elective surgery requiring endotracheal intubation between October
      2002 and June 2003 in a university teaching hospital . All patients were
      premedicated with 5-10mg oral diazepam and randomly assigned to one of two groups
      to receive either suxamethonium as a bolus dose (group A) or atracurium (priming
      with 0.05 mg/kg followed by 0.55 mg/kg after induction of anaesthesia) (group B).
      In both groups, the trachea was intubated when there was maximal muscle
      relaxation, determined clinically by jaw muscle relaxation. Muscle paralysis
      using a PNS, quality of intubating conditions, and occurrence of muscle weakness
      due to the priming dose of atracurium, time to laryngoscopy and onset time were
      all noted. RESULTS: Onset time was 87.1 +/- 25.60s and 135.8 +/- 46.23s in groups
      A and B respectively (P < 0.05). Group A had a laryngoscopy time of 73.6 +/-
      25.22s compared to 107.7 +/- 41.32s in group B (P < 0.05). Intubating conditions
      were significantly better in group A compared to group B (P < 0.05). The
      frequency of muscle weakness from the priming dose of atracurium was 6.6%.
      CONCLUSION: Atracurium, using the priming principle, is an option in our
      environment for modified rapid sequence induction when suxamethonium is
      contraindicated.

PMID- 17203123
TI  - Psychosocial profile of cultists in a Nigerian university: a preliminary report.
AB  - AIMS AND OBJECTIVES: To help stem cult activities on campuses by identifying
      motives for joining cult groups and highlighting psychosocial attributes/profile
      of a potential or already initiated cult member. METHOD: Using snow-balling
      method, 25 consecutive consenting cult members of University of Ilorin were
      interviewed over a six month period using a semi-structured questionnaire. Those
      who had symptoms suggestive of psychiatric disorders were further assessed based
      on ICD-10 criteria. All patients with previous psychiatric illness were excluded.
      RESULT: A significant proportion of the respondents were first year, male,
      previously shy students from high socioeconomic background. There was a
      significant increase in the proportion of respondents who had palpitation,
      sweated more, felt bolder, and became current users of alcohol and tobacco after
      initiation. Also, there was a significant decrease in the proportion of
      respondents who slept well, felt accepted by friends and performed well in
      academic activities after initiation. CONCLUSION: In spite of the small sample
      size and method of data collection, the preliminary findings in this study, could
      be useful in stemming the increasing menace of cultism among students in tertiary
      institutions. It was suggested that control of cult activities should be
      multidimensional with students, parents and university administration taking
      active parts. Establishment of 'Help Centres' on campuses was suggested.

PMID- 17203124
TI  - Pattern of utilisation of eye care services in Benin City, Nigeria.
AB  - Eye care facilities in Nigeria are still not uniformly distributed. Benin City
      has more eye care health facilities than most other parts of the country. This is
      probably due to the privilege of having training schools for both
      Ophthalmologists Ophthalmic Nurses and Optometrists. OBJECTIVE: This study was
      carried out with the aim of determining the pattern of utilisation of available
      eye care services in Benin City by the general public. METHODS: This is a cross
      sectional descriptive study in which 420 staff of ministries were randomly
      selected. With the aid of a self-administered questionnaire, we determined the
      previous use of eye care personnel for those who had had eye complaints in the
      past. The type of services they sought and the eye care personnel involved was
      documented RESULTS: Nearly 72% of respondents had received eye care services from
      professionals, that is ophthalmologists, optometrists and opticians. About 28%
      received treatment from sources that could be considered as inappropriate
      consisting of 14.1% that had self medication, 7.2% from patent medicine shops,
      4.8% from traditional healers and 1.2% on advice from friends. CONCLUSION: Though
      a high percentage of respondents have received treatment for their eye ailments
      from appropriate professionals, an appreciable number still patronise
      inappropriate sources considering that the sampled population were privileged to
      have a minimum basic education .

PMID- 17203125
TI  - Ultrasonic assessment in pre-operative cataract patients.
AB  - INTRODUCTION: The ability to examine the posterior segment of the eye accurately
      in patients with opaque media is essential to good surgical care of the cataract
      patient. In dense cataracts, the posterior segment is inaccessible to direct and
      indirect ophthalmoscopy and so adequate evaluation of posterior segment to
      exclude abnormalities become difficult. There is a risk of poor prognosis in eyes
      of patients with cataracts who may also have co-existing posterior segment
      abnormalities. Ultrasonography provides a method of assessing the structural
      changes in the posterior segment of the eye in such patients. OBJECTIVE: To
      determine the relevance and prevalence of posterior segment abnormalities in
      patients with dense cataracts prior to surgery by ultrasonography. METHOD: A 12-
      month prospective study of patients with clinically diagnosed dense cataracts in
      either or both eyes, in which the posterior segment cannot be evaluated properly
      during ophthalmoscopy, and therefore were sent for ocular ultrasonography. B-scan
      ultrasound was done on 116 eyes of 80 patients. RESULTS: Eighty patients were
      involved in the study, 116 eyes demonstrated dense cataract. One hundred and ten
      eyes (94.8%) had a normal posterior segment. Total retinal detachment was noted
      in 3 eyes (2.59%), a left partial retinal detachment was observed in 1 eye
      (0.87%), 2 eyes with total retinal detachment in conjunction with vitreous
      haemorrhage were noted in a single patient, 1.72% CONCLUSION: Posterior segment
      assessment with ultrasound is advisable and important in the preoperative
      evaluation of patients with dense cataract prior to surgery.

PMID- 17203126
TI  - Seasonal variations in birth weights and gender of infants born in a mission
      hospital in Benin City, Nigeria.
AB  - OBJECTIVE: To examine the relationship, if any, between the geographical season
      in which a baby is born and the baby's birth weight and sex. METHODS: The birth
      weights and sexes of 6141 babies delivered over a five- year period in a Nigerian
      mission hospital were prospectively recorded according to the month and year of
      delivery. The mean birth weights and sexes of infants born in the wet season (May
      to October) were compared with those of their counterparts born in the dry season
      (November to April). RESULTS: Comparison of the mean birth weight during the wet
      and dry seasons showed that for male infants it was 3333 (542)g versus 3197
      (566)g (p<0.01), while for female infants it was 3203 (559)g versus 3110 (601)g
      (p<0.01). When both sexes were combined, the mean birth weights were 3249 (488)g
      and 3164 (524)g in wet and dry seasons respectively(p<0.01). Slightly more boys
      than girls were born in the dry season compared with the wet season (p>0. 05).
      CONCLUSION: Irrespective of gender, babies born during the wet season were
      significantly heavier than their counterparts born during the dry season. There
      was a higher probability of a boy birth in the dry season.

PMID- 17203127
TI  - Prevalence of byssinosis and other respiratory problems among textile mill
      workers in Asaba, Nigeria.
AB  - OBJECTIVES: This study was conducted to determine the distribution and severity
      of byssinosis and other respiratory problems in the different operation sections
      in a textile mill industry in Asaba. PATIENTS AND METHODS: This is a cross
      sectional and analytic study in which workers directly exposed to cotton dust are
      compared with those not directly exposed to cotton dust at one point in time.
      RESULTS: A total of 735 workers were interviewed and 437 workers had respiratory
      examinations carried out on them. Byssinosis was diagnosed in 8 out of 405
      workers (prevalence of 1.98%) who were not directly exposed to cotton dust, and
      21 out of 330 workers (prevalence of 6.36%) who were directly exposed to cotton
      dust. The difference was found to be statistically significant (chi2 =9.25; df=1;
      0.01<p<0.001). The spinning department had the highest prevalence of 11.5%. The
      prevalence of respiratory abnormalities which did not necessarily meet the
      criteria for a diagnosis of byssinosis was 4.9% for persistent cough and
      persistent phlegm; 8.0% for dyspnoea grade 2+; 3.3% for dyspnoea grade 4 and
      2.59% for dyspnoea grade 5. Smoking was not found to be associated with the
      disease as none of the byssinotics were current smokers CONCLUSION: Byssinosis
      and other respiratory problems were found to be more prevalent in sections of the
      textile mill industry that were directly exposed to cotton dust. These findings
      form a basis for making suitable recommendations for the prevention of byssinosis
      and respiratory diseases in textile mills in Nigeria.

PMID- 17203128
TI  - Knowledge, attitude and practices of Nigerian anaesthetists in HIV infected
      surgical patients: a survey.
AB  - In the light of increasing prevalence of the human immunodeficiency virus (HIV),
      anaesthetists are likely to see more patients with this virus in their practice.
      This study evaluated, using a questionnaire format, the knowledge, attitude and
      practices of anaesthetists in the management of HIV infected surgical patients.
      The questionnaire sought demographic information, the knowledge of risks involved
      as well as attitude and practices. One hundred (66.7%) out of 150 questionnaires
      distributed amongst members of the Nigerian Society of Anaesthetists were
      completed and returned. Fifty-five per cent (55%) of the respondents confirmed
      their willingness to be screened but only 45% had had a personal HIV screening
      test. Even though 23% of all the respondents will transfuse unscreened blood in
      an emergency, only 1(8.3%) of the consultants will do so. This trend was also
      reflected in gloving behaviour as 11(91.6%) of consultants will routinely wear
      gloves whilst only 12(70.5%) of the senior house officers will routinely glove
      for venepuncture despite the availability of gloves. Other precautionary
      facilities such as goggles, sharp disposal bins, routine screening of all
      surgical patients were more available in private than in government hospitals.
      Ninety- six per-cent of all respondents will initiate an action after a needle
      stick injury whilst 4% will ignore. General Anaesthesia was the choice of
      anaesthetic in an HIV/AIDS infected patient by 43% of respondents whilst 22% of
      respondents would choose regional technique. However, only 85% of respondents
      were willing to anaesthetise an infected patient. This study suggested a dearth
      of knowledge and perception of risks of HIV/AIDs amongst Nigerian Anaesthetists.
      Appropriate training and greater education is highly recommended. Rigorous
      infection control policy is imperative and hospital authorities must ensure
      availability of protective facilities.

PMID- 17203129
TI  - Endometrial pathology associated with infertility among Nigerian women.
AB  - SUMMARY: One hundred and forty endometrial specimens of women with infertility
      were examined with oil immersion at X100 magnification for evidence of secretory
      activity, presence of any inflammatory cells and characteristic features
      suggestive of specific pathogens. Twenty-three (16.4%) had evidence of chronic
      endometritis the majority being non-specific. Only two (1.4%) were granulomatous.
      There was a significant eosinophilic infiltrate in nine cases (6.4%) some
      numbering up to 55 eosinophils per 5 high power fields (5 hpf). Sensitive
      immunohistochemical techniques would be needed to correlate findings with
      specific pathogens for effective treatment.

PMID- 17203130
TI  - Acute asthma in a children's emergency room: a clinical audit and management
      guideline proposal.
AB  - BACKGROUND: Adequate asthma control in children includes optimal medical
      management of acute exacerbations of the disorder. Asthma guidelines provide
      critical information and serve as quick reference decision-support material for
      clinicians. AIM: This clinical audit aimed at evaluating emergency management of
      acute asthma as well as proposing for use a management protocol, with the view of
      improving quality of care. METHOD: This is a retrospective audit of the
      management of acute asthma over 18 months (October 2000-April 2002) Relevant data
      related to diagnostic and therapeutic procedures in thirty asthmatics were
      extracted and examined. RESULTS: There were 20 males and 10 females (M:F ratio
      2:1). Mean age (range) was 5.9 years (10 months-12.5 years) and mean (range)
      duration of symptoms prior to presentation was 1.9 days (2 hours-8 days). Trigger
      factors, current medications, clinical and functional indices of severity of
      acute asthma were not documented in 73.3%, 93.3% and 96.7% cases respectively.
      Diagnostic labels used in 28 (93.3%) did not reflect the acute nature or severity
      of the acute episode. Although nebulized salbutamol and oral corticosteroids were
      used for 80.0% of cases, aminophylline was frequently prescribed in addition.
      Discharge medications and instructions, including follow up in the respiratory
      clinic were not given in 21 (70.0%) and 28 (93.3%) cases respectively.
      CONCLUSION: This audit noted that the overall management of acute asthma in the
      emergency room and the documentation of crucial information vital in the acute
      and long-term care of asthmatics were inadequate. We propose and recommend for
      use in the Children's Emergency Room, acute asthma management guideline and
      protocol-based asthma paper records as well as computerization of patient
      records.

PMID- 17203131
TI  - Histopathologic analysis of epidermal skin tumours and tumour-like lesions in
      Ahmadu Bello University Teaching Hospital, Zaria.
AB  - OBJECTIVE: A histopathologic analysis of epidermal skin tumours and tumour-like
      lesions seen between 1991 - 2000 in the Department of Pathology, Ahmadu Bello
      University Teaching Hospital [A.B.U.T.H], Zaria is presented. PATIENTS AND
      METHOD: These tumours were classified according to World Health Organisation's
      International Histological Classification for Skin Tumours and were tabulated.
      RESULTS: A total of 350 such lesions comprising 9.9% of all cutaneous neoplasms
      seen within the study period were collected. Overall, they have a male to female
      ratio of 1.7:1. Malignant tumours constituted 72.5%; benign tumours 18.3% and
      tumour-like lesions 9.2%. The commonest malignant lesion was squamous cell
      carcinoma, which constituted 68.3% of all the lesions with a male to female ratio
      of 1.7:1. Epidermal cyst comprised 16.3% with a male to female ratio of 1.5:1.
      CONCLUSION: It is concluded that epidermal tumours and tumour-like lesions are
      not uncommon in Zaria and they show a male preponderance with squamous cell
      carcinoma being the commonest epidermal tumour and it also predominantly affects
      males.

PMID- 17203133
TI  - A highly enantio- and diastereoselective 1,3-dimethylallylation of aldehydes.
AB  - A highly enantio- and diastereoselective pentenylation of aldehydes is described.
      The homoallylic alcohol derived from 1,3-dimethylallylation of (-)-menthone
      undergoes an efficient allyl-transfer reaction with a wide range of aliphatic
      aldehydes in the presence of an acid catalyst to give rise to the corresponding 4
      methyl-2(E)-penten-4-yl-5-ol products in good yields with high enantio- and 4,5
      syn-selectivities.

PMID- 17203134
TI  - Stroop interference, practice, and aging.
AB  - We report two experiments that investigate practice effects on Stroop color-word
      interference in older and younger adults. Both experiments employed a
      computerized, single-item version of the Stroop task with a voice response, and
      both involved practice over hundreds of trials. Both experiments showed generally
      similar practice patterns, including a practice-related reduction in the size of
      the color-word interference effect. However, the older group continued to show a
      larger interference effect throughout practice. These findings indicate that
      older adults show the same trend in practice-related improvement on the Stroop
      task as younger adults.

PMID- 17203135
TI  - Younger and Older Adults' "Good-Enough" Interpretations of Garden-Path Sentences.
AB  - We report 3 experiments that examined younger and older adults' reliance on "good
      enough" interpretations for garden-path sentences (e.g., "While Anna dressed the
      baby played in the crib") as indicated by their responding "Yes" to questions
      probing the initial, syntactically unlicensed interpretation (e.g., "Did Anna
      dress the baby?"). The manipulation of several factors expected to influence the
      probability of generating or maintaining the unlicensed interpretation resulted
      in 2 major age differences: Older adults were generally more likely to endorse
      the incorrect interpretation for sentences containing optionally transitive verbs
      (e.g., hunted, paid), and they showed decreased availability of the correct
      interpretation of subordinate clauses containing reflexive absolute transitive
      verbs (e.g., dress, bathe). These age differences may in part be linked to older
      adults' increased reliance on heuristic-like good-enough processing to compensate
      for age-related deficits in working memory capacity. The results support previous
      studies suggesting that syntactic reanalysis may not be an all-or-nothing process
      and might not be completed unless questions probing unresolved aspects of the
      sentence structure challenge the resultant interpretation.

PMID- 17203136
TI  - Building Research Relationships With Managed Care Organizations: Issues and
      Strategies.
AB  - Managed care is now the dominant form of healthcare in the United States. The
      need for clinical research about the organization, delivery, and outcomes of
      primary care services in managed care models is high, yet access to managed care
      organizations as sites for clinical research may be problematic. The purpose of
      this article is to describe issues involved in obtaining access to managed care
      settings for clinical research and practical strategies for successful
      collaboration using literature review and case description. Three steps for
      developing collaborative relationships with managed care organizations (MCOs) are
      presented: 1) assessment of organizational structure, history, and culture; 2)
      finding common ground; and 3) project implementation. These steps are discussed
      within the context of MCO systems issues and a relationship-centered approach to
      communication between researchers and individuals from the MCO. Successful
      relationships with MCOs for clinical research are possible when careful attention
      is paid to inclusion of MCOs as collaborators in the development of the research
      questions and design, and as partners in the research implementation process.

PMID- 17203138
TI  - Synthesis of constrained analogues of cholecystokinin/opioid chimeric peptides.
AB  - In our ongoing research on the synthesis of constrained analogues of CCK/opioid
      chimeric peptides, a bicyclic dipeptide mimetic for Nle-Asp was designed and
      synthesized. Starting from beta-allyl substituted aspartic acids, the terminal
      double bond was oxidized resulting in spontaneous cyclization to form racemic
      hemiaminals. Allylation of the hemiaminals afforded 5-allyl substituted proline
      analogues, which on oxidation, Horner-Emmons olefination, asymmetric
      hydrogenation, and bicyclization afforded bicyclic dipeptide mimetics for Nle
      Asp. Constrained CCK/opioid peptide analogues containing bicyclic dipeptide
      mimetics for Nle-Gly, Nle-Asp, and homoPhe-Gly were then synthesized and analyzed
      at both the CCK and opioid receptors.

PMID- 17203137
TI  - Modulation of the mirror system by social relevance.
AB  - When we observe the actions of others, certain areas of the brain are activated
      in a similar manner as to when we perform the same actions ourselves. This
      'mirror system' includes areas in the ventral premotor cortex and the inferior
      parietal lobule. Experimental studies suggest that action observation
      automatically elicits activity in the observer, which precisely mirrors the
      activity observed. In this case we would expect this activity to be independent
      of observer's viewpoint. Here we use whole-head magnetoencephalography (MEG) to
      record cortical activity of human subjects whilst they watched a series of videos
      of an actor making a movement recorded from different viewpoints. We show that
      one cortical response to action observation (oscillatory activity in the 7-12 Hz
      frequency range) is modulated by the relationship between the observer and the
      actor. We suggest that this modulation reflects a mechanism that filters
      information into the 'mirror system', allowing only socially relevant information
      to pass.

PMID- 17203139
TI  - Probing the intrinsic features and environmental stabilization of multiply
      charged anions.
AB  - Multiply charged anions (MCAs) represent exotic, highly energetic species in the
      gas-phase due to their propensity to undergo unimolecular decay via electron loss
      or ionic fragmentation. There is considerable fundamental interest in these
      systems since they display novel potential energy surfaces that are characterized
      by Coulomb barriers. Over recent years, considerable progress has been made in
      understanding the factors that affect the stability, decay pathways and
      reactivity of gas-phase MCAs, mainly as a result of the application of
      electrospray ionization as a generic technique for transferring solution-phase
      MCAs into the gas-phase for detailed characterization. We review contemporary
      work in this field, focusing on the factors that control the intrinsic stability
      of MCAs, both as isolated gas-phase ions, and on their complexation with solvent
      molecules and counter-ions. While studies of MCAs are primarily of fundamental
      interest, several classes of important biological ions are commonly observed as
      MCAs in the gas-phase (e.g. oligonucleotides, sugars). Recent results for
      biologically relevant ions are emphasised, since a fundamental understanding of
      the properties of gas-phase MCAs will be highly valuable for developing further
      analytical methods to study these important systems.

PMID- 17203140
TI  - Molecular mechanics methods for predicting protein-ligand binding.
AB  - Ligand binding affinity prediction is one of the most important applications of
      computational chemistry. However, accurately ranking compounds with respect to
      their estimated binding affinities to a biomolecular target remains highly
      challenging. We provide an overview of recent work using molecular mechanics
      energy functions to address this challenge. We briefly review methods that use
      molecular dynamics and Monte Carlo simulations to predict absolute and relative
      ligand binding free energies, as well as our own work in which we have developed
      a physics-based scoring method that can be applied to hundreds of thousands of
      compounds by invoking a number of simplifying approximations. In our previous
      studies, we have demonstrated that our scoring method is a promising approach for
      improving the discrimination between ligands that are known to bind and those
      that are presumed not to, in virtual screening of large compound databases. In
      new results presented here, we explore several improvements to our computational
      method including modifying the dielectric constant used for the protein and
      ligand interiors, and empirically scaling energy terms to compensate for
      deficiencies in the energy model. Future directions for further improving our
      physics-based scoring method are also discussed.

PMID- 17203141
TI  - Extension of molecular electronic structure methods to the solid state:
      computation of the cohesive energy of lithium hydride.
AB  - We describe a simple strategy for calculating the cohesive energy of certain
      kinds of crystal using readily available quantum chemistry techniques. The
      strategy involves the calculation of the electron correlation energies of a
      hierarchy of free clusters, and the cohesive energy E(coh) is extracted from the
      constant of proportionality between these correlation energies and the number of
      atoms in the limit of large clusters. We apply the strategy to the LiH crystal,
      using the MP2 and CCSD(T) schemes for the correlation energy, and show that for
      this material E(coh) can be obtained to an accuracy of approximately 30 meV per
      ion pair. Comparison with the experimental value, after correction for zero-point
      energy, confirms this accuracy.

PMID- 17203142
TI  - Catalytic homogeneous hydrogenation of compounds containing X --> O semipolar
      bonds (X = N, S, P) with para-hydrogen as a promising route for preparation of
      para-water.
AB  - The quantum-chemical simulation (DFT, PBE, TZ2p basis set) of the mechanism of
      catalytic hydrogenation of compounds containing R(n)X --> O semipolar bonds
      (R(n)X = N(2), Me(2)S, C(5)H(5)N, Ph(3)P) on the Wilkinson catalyst
      (Ph(3)P)(3)RhCl with para-hydrogen showed that this process proceeds with
      retention of proton nuclear spin correlation, which enables a principal
      possibility to synthesize para-H(2)O, i.e. the nuclear spin isomer of water with
      antiparallel proton spins, using this route.

PMID- 17203143
TI  - Laser induced fluorescence studies of iodine oxide chemistry. Part II. The
      reactions of IO with CH3O2, CF3O2 and O3.
AB  - The technique of pulsed laser photolysis was coupled to laser induced
      fluorescence detection of iodine oxide (IO) to measure rate coefficients, k for
      the reactions IO + CH(3)O(2)--> products (R1, 30-318 Torr N(2)), IO + CF(3)O(2)-
      > products (R2, 70-80 Torr N(2)), and IO + O(3)--> OIO + O(2) (R3a). Values of
      k(1) = (2 +/- 1) x 10(-12) cm(3) molecule(-1) s(-1), k(2) = (3.6 +/- 0.8) x 10(
      11) cm(3) molecule(-1) s(-1), and k(3a) <5 x 10(-16) cm(3) molecule(-1) s(-1)
      were obtained at T = 298 K. In the course of this work, the product yield of IO
      from the reaction of CH(3)O(2) with I was determined to be close to zero, whereas
      CH(3)OOI was formed efficiently at 70 Torr N(2). Similarly, no evidence was found
      for IO formation in the CF(3)O(2) + I reaction. An estimate of the rate
      coefficients k(CH(3)O(2) + I) = 2 x 10(-11) cm(3) molecule(-1) s(-1) and
      k(CH(3)OOI + I) = 1.5 x 10(-10) cm(3) molecule(-1) s(-1) was also obtained. The
      results on k(1)-k(3) are compared to the limited number of previous
      investigations and the implications for the chemistry of the marine boundary
      layer are briefly discussed.

PMID- 17203144
TI  - VUV photon induced fluorescence study of SF5CF3.
AB  - The interaction of SF(5)CF(3) with vacuum-UV radiation has been investigated by
      photon induced fluorescence spectroscopy. Total fluorescence yield and dispersed
      fluorescence spectra of SF(5)CF(3) were recorded in the 200-1000 nm fluorescence
      window. In all cases, the fluorescence spectra resemble those of CF(3)X (X = H,
      F, Cl, and Br) molecules. At photon energies below 20 eV, the emission is
      attributed to the excited CF(3) and CF(2) fragments. The threshold for the CF(3)
      emission is 10.2 +/- 0.2 eV, giving an upper limit estimate for the SF(5)-CF(3)
      bond dissociation energy of 3.9 +/- 0.3 eV. The excitation functions of the CF(3)
      and CF(2) emissions were measured in the photon energy range 13.6-27.0 eV. The
      resonant structures observed in SF(5)CF(3) are attributed to electronic
      transitions from valence to Rydberg orbitals, following similar assignments in
      CF(3)X molecules. The photoabsorption spectrum of SF(5)CF(3) shows features at
      the same energies, indicating a strong contribution from Rydberg excitations.

PMID- 17203145
TI  - A computational modelling study of oxygen vacancies at LaCoO3 perovskite
      surfaces.
AB  - Atomistic computational modelling of the surface structure of the catalytically
      active perovskite LaCoO(3) has been undertaken in order to develop better models
      of the processes involved during catalytic oxidation processes. In particular,
      the energetics of creating oxygen ion vacancies at the surface have been
      investigated for the three low index faces (100), (110) and (111). Two mechanisms
      for vacancy creation have been considered involving dopant Sr(2+) cations at the
      La(3+) site and reduction of Co(3+) to Co(2+). For both mechanisms, there is a
      general tendency that the smaller the cation defect separation, the lower the
      energy of the cluster, as would be expected from simple electrostatic
      considerations. In addition, there are clear indications that oxygen vacancies
      are more easily created at the surface than in the bulk. The results also confirm
      that the presence of defects strongly influences crystal morphology and surface
      chemistry. The importance of individual crystal surfaces in catalysis is
      discussed in terms of the energetics for the creation of oxygen vacancies.

PMID- 17203147
TI  - A femtosecond time-resolved investigation of dual fluorescence from N6,N6
      dimethyladenine.
AB  - The excited electronic state dynamics of N(6),N(6)-dimethyladenine (DMAde), a
      molecule known to emit dual fluorescence, has been studied in aqueous solution
      using femtosecond fluorescence up-conversion spectroscopy. Time profiles of the
      fluorescence of DMAde excited at lambda= 258 nm were measured at a series of
      wavelengths in the range 320 nm <or=lambda(fl)<or= 650 nm. At wavelengths in the
      near UV (lambda(fl)<or= 420 nm), the time profiles were dominated by a very short
      lived decay component with a lifetime between 0.2 ps <or=tau(1)<or= 0.6 ps,
      depending on the detection wavelength. Two other components with lifetimes of
      tau(2) approximately 3.5 ps and tau(3) approximately 60 ps gave minor
      contributions. In the emission observed at longer wavelengths (lambda(fl)>or= 500
      nm), which appeared slightly delayed compared to the UV fluorescence, the long
      lived fluorescence component (tau(3)) dominated, the second component (tau(2))
      disappeared. The results are consistent with the assumption that DMAde is
      primarily excited to a short-lived local excited (LE) electronic state that
      fluoresces mostly in the UV and decays rapidly, on a approximately 0.5 ps
      timescale, to an intramolecular charge transfer (ICT) state that emits only at
      longer wavelengths in the visible spectrum. The fluorescence-time profiles and
      transient fluorescence spectra reconstructed from the time profiles provided
      further information on secondary relaxation processes within and between the
      excited states and their non-radiative relaxation to the electronic ground state.

PMID- 17203146
TI  - An NMR strategy for obtaining multiple conformational constraints for 15N-13C
      spin-pair labelled organic solids.
AB  - This work demonstrates a solid-state NMR strategy for extracting multiple
      interatomic distance and angle constraints from moderately complex solid organic
      compounds containing a single (13)C label and a single (15)N label. It is shown
      that the constraints obtained for the compound cimetidine, with the labels placed
      at positions directed by the standard synthetic route, are sufficient to provide
      reliable estimates of 5 of the 8 torsional degrees of freedom in the molecule and
      are consistent with a molecular conformation close to that determined by
      crystallography. This strategy will be useful for determining the conformations
      of sparsely-labelled small molecules in motionally restrained environments, such
      as within the binding sites of membrane-embedded receptors.

PMID- 17203148
TI  - The atmospheric photolysis of E-2-hexenal, Z-3-hexenal and E,E-2,4-hexadienal.
AB  - The atmospheric photolysis of E-2-hexenal, Z-3-hexenal and E,E-2,4-hexadienal has
      been investigated at the large outdoor European Photoreactor (EUPHORE) in
      Valencia, Spain. E-2-Hexenal and E,E-2,4-hexadienal were found to undergo rapid
      isomerization to produce Z-2-hexenal and a ketene-type compound (probably E-hexa
      1,3-dien-1-one), respectively. Both isomerization processes were reversible with
      formation of the reactant slightly favoured. Values of j(E-2-hexenal)/j(NO(2)) =
      (1.80 +/- 0.18) x 10(-2) and j(E,E-2,4-hexadienal)/j(NO(2)) = (2.60 +/- 0.26) x
      10(-2) were determined. The gas phase UV absorption cross-sections of E-2-hexenal
      and E,E-2,4-hexadienal were measured and used to derive effective quantum yields
      for photoisomerization of 0.36 +/- 0.04 for E-2-hexenal and 0.23 +/- 0.03 for E,E
      2,4-hexadienal. Although photolysis appears to be an important atmospheric
      degradation pathway for E-2-hexenal and E,E-2,4-hexadienal, the reversible nature
      of the photolytic process means that gas phase reactions with OH and NO(3)
      radicals are ultimately responsible for the atmospheric removal of these
      compounds. Atmospheric photolysis of Z-3-hexenal produced CO, with a molar yield
      of 0.34 +/- 0.03, and 2-pentenal via a Norrish type I process. A value of j(Z-3
      hexenal)/j(NO(2)) = (0.4 +/- 0.04) x 10(-2) was determined. The results suggest
      that photolysis is likely to be a minor atmospheric removal process for Z-3
      hexenal.

PMID- 17203149
TI  - Excited state dynamics and fragmentation channels of the protonated dipeptide H2N
      Leu-Trp-COOH.
AB  - The excited state dynamics of the isolated and protonated peptide H(2)N-Leu-Trp
      COOH are analyzed by fs pump-probe spectroscopy. The peptides are brought into
      the gas phase by electrospray ionization, and fs pump-probe excitation is
      detected by fragment ion formation. The pump laser addressed the excited pipi*
      state of the indole chromophore of the amino acid tryptophan. The subsequent
      excited state dynamics agreed with a biexponential decay with time constants of
      500 fs and 10 ps. This is considerably shorter than the lifetime of neutral
      tryptophan in solution and in proteins, but similar to isolated, protonated
      tryptophan. Several models are discussed to explain the experimental results but
      the detailed quenching mechanism remains unresolved.

PMID- 17203151
TI  - PDMS absorption of small molecules and consequences in microfluidic applications.
AB  - Microfluidic devices made out of polydimethylsiloxane (PDMS) have many physical
      properties that are useful for cell culture applications, such as transparency
      and gas permeability. Another distinct characteristic of PDMS is its ability to
      absorb hydrophobic small molecules. Partitioning of molecules into PDMS can
      significantly change solution concentrations and could potentially alter
      experimental outcomes. Herein we discuss PDMS absorption and its potential impact
      on microfluidic experiments.

PMID- 17203152
TI  - Multiphase microfluidics: from flow characteristics to chemical and materials
      synthesis.
AB  - We review transport characteristics of pressure-driven, multiphase flows through
      microchannel networks tens of nanometres to several hundred of micrometres wide
      with emphasis on conditions resulting in enhanced mixing and reduced axial
      dispersion. Dimensionless scaling parameters useful in characterizing multiphase
      flows are summarized along with experimental flow visualization techniques.
      Static and dynamic stability considerations are also included along with methods
      for stabilizing multiphase flows through surface modifications. Observed gas
      liquid and immiscible liquid-liquid flows are summarized in terms of flow regime
      diagrams and the different flows are related to applications in chemistry and
      materials synthesis. Means to completely separate multiphase flows on the
      microscale and guidelines for design of scalable multiphase systems are also
      discussed.

PMID- 17203153
TI  - A micromachined interface for airborne sample-to-liquid transfer and its
      application in a biosensor system.
AB  - A novel micromachined interface for airborne sample-to-liquid adsorption and
      droplet-to-liquid transfer was designed and fabricated. It enables a robust sheet
      liquid flow serving as an adsorption site. The interface was characterised for
      flow and pressure properties and tested successfully for the transfer/adsorption
      of different samples. A qualitative theoretical model of the device
      characteristics is presented. We also used the interface to introduce a novel
      method and system for fast detection of dust- and vapour-based narcotics and
      explosives traces. The microfluidic vapour-to-liquid adsorption interface was
      coupled to a set of downstream QCM sensors. The system was tested successfully,
      with 50 ng cocaine samples rendering 15 Hz frequency shifts and with 100 ng
      heroine samples rendering 50 Hz frequency shifts. Gravitation invariance of the
      open liquid interface was demonstrated successfully, with the interface mounted
      upside down as well as vertically. The detection time was reduced to half of the
      time needed in previous systems. Machine size, weight and cost were reduced.

PMID- 17203155
TI  - Active control of the depletion boundary layers in microfluidic electrochemical
      reactors.
AB  - In this paper, we describe three methods to improve the performance of pressure
      driven laminar flow-based microreactors by manipulating reaction-depletion
      boundary layers to overcome mass transfer limitations at reactive surfaces on the
      walls, such as electrodes. The transport rate of the reactants to the reactive
      surfaces is enhanced by (i) removing the depleted zone through multiple
      periodically-placed outlets; (ii) adding fresh reactants through multiple
      periodically-placed inlets along the reactive surface; or (iii) producing a
      spiraling, transverse flow through the integration of herringbone ridges along
      the channel walls. For approaches (i) and (ii), the network of microfluidic
      channels needs to be designed such that under the operating conditions used the
      right amount of boundary layer at each outlet or inlet is removed or replenished,
      respectively. Here, we report a set of design rules, derived with the help of a
      fluidic resistance circuit model, to aid in the design of appropriate
      microfluidic networks. Also, the actual enhancement of the performance of the
      electrochemical microreactor, i.e. chemical conversion efficiency, using multiple
      inlets, multiple outlets, or herringbone ridges is reported.

PMID- 17203154
TI  - Open-access microfluidic patch-clamp array with raised lateral cell trapping
      sites.
AB  - A novel open-access microfluidic patch-clamp array chip with lateral cell
      trapping sites raised above the bottom plane of the chip was developed by
      combining both a microscale soft-lithography and a macroscale polymer fabrication
      method. This paper demonstrates the capability of using such an open-access
      fluidic system for patch-clamp measurements. The surface of the open-access patch
      clamp sites prepared by the macroscale hole patterning method of soft-state
      elastic polydimethylsiloxane (PDMS) is examined; the seal resistances are
      characterized and correlated with the aperture dimensions. Whole cell patch-clamp
      measurements are carried out with CHO cells expressing Kv2.1 ion channels. Kv2.1
      ion channel blocker (TEA) dosage response is characterized and the binding
      activity is examined. The results demonstrate that the system is capable of
      performing whole cell measurements and drug profiling in a more efficient manner
      than the traditional patch-clamp set-up.

PMID- 17203156
TI  - Electroosmotic flow patterning using microfluidic delay loops.
AB  - A theoretical and experimental investigation of alternating electroosmotic flow
      patterns by means of specially designed delay loops is presented. Using
      elementary methods of compact network modeling and detailed FEM simulations the
      flow behavior and, in particular, the rearrangement of sample plugs is modeled.
      The proposed designs rely on flow splitting in combination with electroosmotic
      delay loops leading to a runtime difference or phase shift between two sub
      streams. Due to this phase shift, a new fluid interface is generated at the
      merging point. The approach is experimentally validated by injection of a
      Rhodamine 6G solution into an aqueous sodium tetraborate buffer.

PMID- 17203157
TI  - A multielectrode microcompartment culture platform for studying signal
      transduction in the nervous system.
AB  - This paper describes the design, fabrication, and characterization of a
      microfabricated compartmented culture system (micro-CCS) useful for
      electrophysiological signaling studies in cultured neurons. The focus of the
      paper is the process of interfacing the micro-CCS with cultured neurons and to
      demonstrate the applicability of the system for biochemical-mediated
      electrophysiological studies. Moreover, we show that we can record action
      potentials from cultured neurons through the extracellular compartmented
      application of elevated levels of K(+) ions. Finally, we show that we can isolate
      the electrophysiological effects of the sodium channel blocker tetrodotoxin in
      one of the compartments of a two compartment culture while recording
      electrophysiological data from both compartments.

PMID- 17203159
TI  - Optical force field mapping in microdevices.
AB  - We present a method for characterizing microscopic optical force fields. Two
      dimensional vector force maps are generated by measuring the optical force
      applied to a probe particle for a grid of particle positions. The method is used
      to map out the force field created by the beam from a lensed fiber inside a
      liquid filled microdevice. We find transverse gradient forces and axial
      scattering forces on the order of 2 pN per 10 mW laser power which are constant
      over a considerable axial range (>35 microm). These findings suggest future
      useful applications of lensed fibers for particle guiding/sorting. The propulsion
      of a small particle at a constant velocity of 200 microm s(-1) is shown.

PMID- 17203158
TI  - Ultrasonic standing wave manipulation technology integrated into a
      dielectrophoretic chip.
AB  - Several cell-based biological applications in microfluidic systems require
      simultaneous high-throughput and individual handling of cells or other
      bioparticles. Available chip-based tools for contactless manipulation are
      designed for either high-precision handling of individual particles, or high
      throughput handling of ensembles of particles. In order to simultaneously perform
      both, we have combined two manipulation technologies based on ultrasonic standing
      waves (USWs) and dielectrophoresis (DEP) in a microfluidic chip. The principle is
      based on the competition between long-range ultrasonic forces, short-range
      dielectrophoretic forces and viscous drag forces from the fluid flow. The
      ultrasound is coupled into the microchannel resonator by an external transducer
      with a refractive element placed on top of the chip, thereby allowing
      transmission light microscopy to continuously monitor the biological process. The
      DEP manipulation is generated by an electric field between co-planar
      microelectrodes placed on the bottom surface of the fluid channel. We demonstrate
      flexible and gentle elementary manipulation functions by the use of USWs and
      linear or curved DEP deflector elements that can be used in high-throughput
      biotechnology applications of individual cells.

PMID- 17203160
TI  - PDMS bonding by means of a portable, low-cost corona system.
AB  - A hand-held corona treater is presented as an effective, inexpensive, and
      portable alternative for irreversible bonding of polydimethylsiloxane (PDMS) to
      glass.

PMID- 17203161
TI  - Expression of the Endothelin-axis in the different histologic subtypes of renal
      cell carcinoma: a tissue microarray analysis.
AB  - Endothelin-1 and its receptors ETAR and ETBR, commonly referred to as the
      Endothelin-axis, are emerging to play a role in cancer. The Endothelin-axis has
      been shown to be involved in proliferation, angiogenesis and metastasis in
      various human tumours. To assess the role of the Endothelin-axis in renal cell
      carcinoma, we analysed its expression in archival tumour tissue of 183 patients.
      Representative tumour blocks were selected for constructing a tissue microarray.
      Paraffin sections were assessed immunohistochemically using monoclonal and
      polyclonal antibodies for Endothelin-1, ETAR and ETBR. Staining intensities were
      analysed semiquantitatively and the results were correlated with various
      histopathologic factors. Overexpression of Endothelin-1, ETAR and ETBR was
      identified in 12.8%, 84.1% and 93.3% of cases, respectively. No association with
      pathological tumour stage and histologic grading was found. Papillary renal cell
      carcinomas expressed highly significantly more Endothelin-1 than clear cell renal
      cell carcinomas (34.5% vs. 6.7%, p<0.001), while there was no difference between
      ETAR- and ETBR-expression in these histologic subtypes. However, ETAR tended to
      be overexpressed in the subgroup of G3-tumours (p=0.044). Studies are underway
      assessing the role of the Endothelin-axis and its potential use as a molecular
      target in renal cell carcinoma.

PMID- 17203162
TI  - Expression levels of eIF4E, VEGF, and cyclin D1, and correlation of eIF4E with
      VEGF and cyclin D1 in multi-tumor tissue microarray.
AB  - The mRNA cap-binding protein, eukaryotic initiation factor 4E (eIF4E), is a rate
      limiting factor of cap-dependent translation initiation. When elevated, eIF4E
      greatly facilitates translation of a selected spectrum of mRNAs coding for
      proteins critical to angiogenesis and growth such as vascular endothelial growth
      factor (VEGF) and cyclin D1. Expression levels of eIF4E, VEGF, and cyclin D1 were
      examined in multi-tumor tissue microarray by immunohistochemistry and analyzed
      quantitatively. eIF4E, VEGF and cyclin D1 protein were elevated in tumors of the
      breast (62, 78, or 40%), colon (72, 77, or 12%), glioblastoma multiforme (48, 68,
      or 52%), lymphoma (66, 74, or 38%), melanoma (59, 73, or 58%), NSCLC (81, 82, or
      29%), ovary (50, 39, or 13%), and prostate (78, 97, or 21%), respectively. eIF4E
      levels were strongly correlated with VEGF and cyclin D1 in melanoma (Spearman's
      r=0.97 and 0.77; all P<0.0001); moderately in tumors of the breast (r=0.55 and
      0.41; all P<0.0005), colon (0.63 and 0.56; all P<0.0001), lung (0.53 and 0.53;
      all P<0.005), lymphoma (0.50 and 0.61; all P<0.0005), prostate (0.46 and 0.54;
      all P<0.005), or ovary (0.56 and 0.46; all P<0.005); and weakly in tumors of
      glioblastoma multiforme (r=0.20 and 0.31; all P>0.15). The significant
      association of eIF4E with VEGF and cyclin D1 in multiple tumors supports a role
      for eIF4E in translational regulation of proteins related to angiogenesis and
      growth.

PMID- 17203163
TI  - Antitumor effects of ZD6474 on head and neck squamous cell carcinoma.
AB  - Angiogenesis is required for tumor growth and metastasis and, therefore,
      represents a target for cancer treatment. While many factors have been implicated
      in promoting angiogenesis, vascular endothelial growth factor (VEGF) plays a key
      role in tumor angiogenesis. ZD6474 is a potent VEGF receptor-2 (VEGFR-2) tyrosine
      kinase inhibitor which also has activity against the epidermal growth factor
      receptor (EGFR) tyrosine kinase. The purpose of this study was to investigate the
      sensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines to
      ZD6474, and to evaluate its antitumor efficacy on HNSCC xenografts. This is the
      first demonstration of antitumor effects of ZD6474 on HNSCC. In vitro ZD6474
      displayed antiproliferative effects on HNSCC cells and inhibition of VEGFR-2 and
      EGFR pathways. In vivo ZD6474 displayed antitumor activity, induced apoptosis and
      antiangiogenic activity on nude mice bearing an established xenograft of YCU-H891
      cells. These results suggest that ZD6474 has the potential to inhibit two key
      pathways in tumor growth via inhibition of VEGF-dependent tumor angiogenesis and
      via inhibition of EGFR-dependent tumor cell proliferation.

PMID- 17203164
TI  - Dietary beta-cryptoxanthin inhibits N-butyl-N-(4-hydroxybutyl)nitrosamine-induced
      urinary bladder carcinogenesis in male ICR mice.
AB  - Recent epidemiological studies have indicated that high dietary consumption of
      fruit and vegetables results in lower risk of bladder cancer. To confirm these
      findings, we investigated in the current study the effects of dietary
      administration with beta-cryptoxanthin extracted from Citras unshiu oranges on N
      butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary bladder
      carcinogenesis in mice. Male ICR mice were divided into 6 experimental and
      control groups. Groups 1 through 4 were given OH-BBN (500 ppm) in drinking water
      for 6 weeks to induced urinary bladder neoplasms. Mice in groups 2, 3 and 4 were
      fed the diets mixed with 1, 5 and 25 ppm of beta-cryptoxanthin, respectively,
      starting 1 week after the cessation of OH-BBN exposure, and kept on these diets
      for 24 weeks until the termination of the study. Group 5 was treated with the
      diet containing the test compound (25 ppm) alone, and group 6 served as an
      untreated control. All animals were sacrificed at week 32 for histopathology and
      immunohistochemistry (cyclin D1). Feeding with beta-cryptoxanthin decreased the
      incidence and multiplicity of preneoplastic and neoplastic lesions of urinary
      bladder. Notably, the highest dose (25 ppm) of the test chemical significantly
      lowered the occurrence of bladder carcinoma, in conjunction with reducing the
      cyclin D1-positive cell ratio. These findings suggest that beta-cryptoxanthin is
      able to prevent OH-BBN-induced bladder carcinogenesis in mice.

PMID- 17203165
TI  - Overexpression of aldo-keto reductase 1C2 as a high-risk factor in bladder
      cancer.
AB  - Intravesical adjuvant chemotherapy and neoadjuvant chemotherapy has been
      respectively administered for superficial transitional cell carcinoma (TCC) of
      urinary bladder and advanced TCC for years. However, the therapeutic efficacy is
      limited. Recently, overexpression of aldo-keto reductase (AKR) in lung,
      esophageal, uterine cervical and ovarian cancers was shown to be closely
      associated with disease progression and drug resistance. In this study, we used
      immunohistochemistry to determine AKR expression in pathological specimens of 347
      patients with urinary bladder cancer (UBC). Some of these patients were from
      areas with a high risk of black foot disease (BFD), a disease that is closely
      associated with arsenic contamination of drinking water. The presence of AKR was
      confirmed by immunoblotting, matrix-assisted laser desorption/ ionization time of
      flight mass spectrometry (MALDI-TOF) and reverse transcription-polymerase chain
      reaction (RT-PCR). AKR isotype was determined by cDNA sequencing. Our results
      showed overexpression of AKR1C2 in 226 (65.1%) patients. BFD areas had a higher
      frequency of patients expressing AKR1C2 in UBC. Among AKR1C2-positive UBC, 148
      (65.5%) were invasive, 70 (31.0%) were non-invasive and 8 (3.5%) were carcinoma
      in situ (CIS). These data indicated that AKR1C2 expression could be significantly
      associated with cancer invasiveness (p<0.001) and disease progression. Because
      BFD has been closely related to arsenic ingestion, our results suggested that
      continual intake of arsenic in drinking water might provoke AKR1C2 expression
      that could in turn induce drug resistance in UBC, and AKR1C2 could be a tumor
      marker for UBC.

PMID- 17203166
TI  - Gefitinib induces premature senescence in non-small cell lung cancer cells with
      or without EGFR gene mutation.
AB  - Despite its tremendous antitumor effect in a subset of patients with non-small
      cell lung cancer (NSCLC), the exact mechanism of gefitinib-induced cell death has
      not been fully determined. In this study, forms of cell death in various NSCLC
      cell lines after gefitinib exposure was analyzed to elucidate the cell death
      mechanism of gefitinib. Though higher concentration of gefitinib (10 microM)
      induced extensive apoptosis in two cell lines (EGFR-mutated PC-9 cells and EGFR
      wild- type EBC-2/R cells), clinically relevant concentrations of gefitinib (1
      microM) induced prominent premature senescence instead of apoptosis in these
      cells. This induction of senescence was preceded by immediate increase of
      p16INK4A, p21WAF1/Cip1 and p27Kip1 levels and subsequent G1 cell cycle arrest.
      These phenomena were not observed in gefitinib-resistant (RERF-LC-MS) cells.
      Additionally, ex vivo exposure to gefitinib induced senescence in short-term
      cultured tumor cells that were obtained from malignant pleural effusion of a
      patient with NSCLC, whose tumor was later revealed to be clinically sensitive to
      gefitinib. Our results indicate that senescence might be a major anti-tumor
      mechanism of gefitinib in these NSCLC cells regardless of the EGFR gene mutation
      status.

PMID- 17203167
TI  - EGFRvIII mutation in lung cancer correlates with increased EGFR copy number.
AB  - Overexpression of the epidermal growth factor receptor (EGFR) is caused by EGFR
      gene amplification and is sometimes associated with expression of a variant EGFR
      (deletion exon 2-7 or EGFRvIII). EGFRvIII mutation has oncogenic potential and is
      investigated as a potential therapeutic target. We genotyped the EGFRvIII
      mutation status in 252 surgically treated lung cancer cases. The presence or
      absence of EGFRvIII mutation was analyzed by real-time quantitative polymerase
      chain reaction (PCR) with mutation specific sensor and anchor probes. EGFR copy
      number was evaluated with PCR-based assay. EGFR mutation status at kinase domain
      has been examined and reported. EGFRvIII mutation was found on 8 of 252 patients.
      All patients were male, smokers, and 7 had squamous cell carcinoma. The mutation
      status was significantly correlated with pathological subtypes (squamous cell
      carcinoma vs. adenocarcinoma, p=0.0114). Sixty EGFR mutations at kinase domain
      exclusively existed with EGFRvIII mutations. EGFR gene copy number was
      significantly higher in EGFRvIII mutant (4.711+/-4.968) than in non-EGFRvIII
      mutant (2.284+/-1.224) (p=0.0001). EGFRvIII gene mutation might be one of the
      mechanisms of increased EGFR copy number. Further studies are needed to confirm
      the mechanisms of EGFRvIII mutations for possible anti-EGFR therapy for lung
      cancer.

PMID- 17203168
TI  - Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase
      genes predict response and toxicity to capecitabine-raltitrexed in colorectal
      cancer.
AB  - Pharmacogenetics is an increasingly useful field where the genetic studies are
      becoming an important tool for predicting drug toxicity and/or efficacy.
      Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene
      polymorphisms could be highly informative tools in the clinical handling of
      colorectal cancer patients, who are following fluoropyrimidine based
      chemotherapy. Fifty-eight patients, with non-resectable metastatic colorectal
      cancer, were treated with capecitabine and raltitrexed, every three weeks.
      Patients were divided in a good-response group (complete and partial response)
      and a poor-response group (stable and progression). A genotype panel TS-DPD was
      evaluated. Results show that TS genotype analysis clearly differentiates patients
      with a worst response to a 5-fluorouracil based chemotherapy. DPD genotype was
      shown to be highly informative for prediction of toxicity of the treatment. These
      polymorphisms could represent an accurate, rapid and effective determination
      panel, indicative of resistance and toxicity for patients undergoing
      fluoropyrimidine based treatment.

PMID- 17203169
TI  - Immortalized ovarian surface epithelial cells acquire tumorigenicity by
      Acrogranin gene overexpression.
AB  - Malignant transformation is caused by multi-step genetic mutations, and growth
      factors are believed to play important roles in developing and maintaining
      malignant phenotype. However, there is no direct evidence that a specific growth
      factor contributes to malignant transformation of phenotypically normal cells. In
      order to assess the function of Acrogranin (also known as granulin epithelial
      precursor; GEP) in ovarian carcinogenesis, ovarian surface epithelial (OSE)
      cells, which are supposed to be the origin of primary ovarian epithelial cancer,
      were transfected with combined genes of hTERT, SV40 LT, and Acrogranin.
      Introduction of hTERT and SV40 LT was sufficient for immortalizing OSE cells but
      not enough for tumor formation in nude mice. In contrast, transfection and
      overexpression of Acrogranin in immortalized OSE cells showed augmented
      clonogenicity in soft agar and obvious tumorigenicity in nude mice. This is the
      first study showing evidence that a specific growth factor plays a direct role in
      malignant transformation in ovarian cancer development.

PMID- 17203170
TI  - Establishment and characterization of a human adenoid cystic carcinoma cell line
      forming colonies cultured in collagen gel and transplantable in nude mice.
AB  - We established a new cell line (ACCNS) from human adenoid cystic carcinoma (AdCC)
      of the maxilla, using tissue culture techniques and it has been successfully
      subcultured for more than 100 passages during 2 years. The population doubling
      time was approximately 39.2 h on a plastic dish. In type I collagen gel culture,
      the cells formed spherical colonies by day 7 after seeding. The colonies showed
      tubular and solid structures, and eosinophilic material stained with mucicarmine
      was revealed in the inner space. Immunohistochemically, ACCNS cells demonstrated
      expressions of keratin, alpha-smooth muscle actin, vimentin and S-100 protein,
      similar to those of original AdCC. These findings indicate that ACCNS cells
      possess the characteristics of AdCC. In addition, inoculation of 4.0x10(6) cells
      into nude mice developed tumors that were histologically confirmed as
      undifferentiated carcinoma. Therefore, ACCNS is the first AdCC cell line with
      tumorigenicity in nude mice. Based on these results, ACCNS provides a useful
      culture model of AdCC to analyze the biological characteristics and behavior of
      this tumor.

PMID- 17203171
TI  - Reciprocal expression of CCAAT/enhancer binding proteins alpha and beta in
      hepatoblastomas and its prognostic significance.
AB  - Hepatoblastoma is one of the common pediatric solid tumors with frequent mutation
      of the beta-catenin gene which might be an early event of its carcinogenesis.
      However, the detailed molecular mechanism is still unknown. We studied the
      expression levels of CCAAT/enhancer binding protein alpha (C/EBPalpha) and
      C/EBPbeta, which regulate differentiation and growth of embryonic hepatocytes, to
      establish whether or not they were involved in affecting the clinical behavior of
      hepatoblastoma. The quantitative real-time reverse transcriptase-PCR revealed
      that expression of C/EBPalpha mRNA was significantly up-regulated in tumors 223%
      (p=0.013) as compared with that in adjacent normal livers, while expression of
      C/EBPbeta was down-regulated to 27% (p=0.002). Of interest, the
      immunohistochemical analysis showed that expression of C/EBPalpha was higher and
      that of C/EBPbeta lower in the poorly differentiated tumor cells than in the well
      differentiated cells within the same tumor. Furthermore, high expression of
      C/EBPalpha (p=0.047) as well as low expression of C/EBPbeta (p=0.025) was
      significantly associated with poor prognosis of the patients. Cox hazard model
      suggested that expression of C/EBPalpha and that of C/EBPbeta were independent
      indicators to predict the prognosis from age but not from histology. Thus,
      expression of C/EBP proteins may play an important role in the genesis and
      clinical behavior of hepatoblastoma probably by inducing different stages of
      arrest of differentiation.

PMID- 17203172
TI  - Expression of protease activated receptor-2 related to angiogenesis in tumor
      advancement of uterine endometrial cancers.
AB  - Protease activated receptor-2 (PAR-2) is the second member of a novel family of G
      protein coupled seven-transmembrane domain receptors. PAR-2 has been reported to
      be expressed in various tumors and play a vital role in the regulation of cancer
      cell growth. The purpose of this study was to clarify the roles of PAR-2 in the
      angiogenic pathway in uterine endometrial cancers. PAR-2 expression was analyzed
      in 61 uterine endometrial cancer and 15 normal endometrium tissue specimens. PAR
      2 histoscores and mRNA levels were determined by immunohistochemistry and real
      time RT-PCR, respectively. Microvessel counts were determined by
      immunohistochemistry for CD31 and factor VIII-related antigen. The localization
      of PAR-2 was dominant in the cancer cells of endometrial cancer tissues of all
      cases studied. PAR-2 histoscores highly correlated with PAR-2 mRNA levels in the
      same tissues (r=0.87, p<0.001). PAR-2 histoscores and mRNA levels both
      significantly increased in uterine endometrial cancers with clinical stages
      (I<II<III, p<0.001), dedifferentiation (G1<G2<G3, p<0.001) and myometrial
      invasion (A<B, p<0.001; B<C, p<0.05) in comparison to normal endometria. There
      were significant correlations between PAR-2 histoscores and mRNA levels with
      microvessel counts in uterine endometrial cancers. PAR-2 was upregulated during
      uterine endometrial cancer progression with dedifferentiation and myometrial
      invasion. Therefore, PAR-2 might work on tumor advancement of uterine endometrial
      cancers via angiogenic activity.

PMID- 17203173
TI  - Conditional nuclear localization of hMLH3 suggests a minor activity in mismatch
      repair and supports its role as a low-risk gene in HNPCC.
AB  - DNA mismatch repair (MMR) mechanism contributes to the maintenance of genomic
      stability. Loss of MMR function predisposes to a mutator cell phenotype,
      microsatellite instability (MSI) and cancer, especially hereditary non-polyposis
      colorectal cancer (HNPCC). To date, five MMR genes, hMSH2, hMSH6, hMLH1, hPMS2,
      and hMLH3 are associated with HNPCC. Although, hMLH3 is suggested to be causative
      in HNPCC, its relevance to MMR needs to be confirmed to reliably assess
      significance of the inherited sequence variations in it. Recently, a human
      heterodimer hMLH1/hMLH3 (hMutLgamma) was shown to be able to assist hMLH1/hPMS2
      (hMutLalpha) in the repair of mismatches in vitro. To repair mismatches in vivo,
      hMLH3 ought to localize in the nucleus. Our immunofluorescence analyses indicated
      that when all the three MutL homologues are natively expressed in human cells,
      endogenous hMLH1 and hPMS2 localize in the nucleus, whereas hMLH3 stays in the
      cytoplasm. Absence of hPMS2 and co-expression of hMLH3 with hMLH1 results in its
      partial nuclear localization. Our results are clinically relevant since they show
      that in the nuclear localization hMLH3 is dependent on hMLH1 and competitive with
      hPMS2. The continuous nuclear localization of hMLH1 and hPMS2 suggests that in
      vivo, hPMS2 (hMutLalpha) has a major activity in MMR. In absence of hPMS2, hMLH3
      (hMutLgamma) is located in the nucleus, suggesting a conditional activity in MMR
      and supporting its role as a low-risk gene in HNPCC.

PMID- 17203174
TI  - Cell cycle regulating proteins p21 and p27 in prognosis of oral squamous cell
      carcinomas.
AB  - Cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDKIs),
      such as p21 and p27, exert a direct control on the cell cycle. p21 and p27 are
      negative regulators of cyclin-dependent kinases and in this function they are
      negative check-point regulators of the cell cycle. We therefore aimed to evaluate
      p21 and p27 expression in oral squamous cell carcinomas (OSSC) to determine the
      value as a prognostic marker. One hundred and ninety-two patients with
      histologically proven, surgically treated squamous cell carcinoma of the oral
      cavity were eligible for the study and investigated for the expression of p21 and
      p27 by means of tissue microarrays (TMAs). Immunohistochemical screening under
      identical condition were carried out with antibodies against p21 and p27.
      Correlations between clinical features and the expression of the respective
      antibodies were evaluated statistically by Kaplan-Meier curves, log-rank and
      chi(2) tests. The expression of p21 correlated significantly with an increased
      prognosis in the log-rang test (p=0.01). No significant correlation was found
      between the expression of p27 and the overall survival rate. In multivariate Cox
      analysis, p27 was indicated as independent predictor of survival prognosis in the
      subgroup of nodal positive carcinomas, p27 positive tumours showed a
      significantly better survival prognosis (p=0.03). p21 and p27 in carcinoma of
      oral cavity seem to be predictive parameter in regulation and prognosis of
      squamous cell carcinomas. A p21 negative subgroup of OSCC may benefit from
      additional radio or radiochemotherapy.

PMID- 17203175
TI  - The expression of low density lipoprotein receptor-related protein in colorectal
      carcinoma.
AB  - Low density lipoprotein receptor-related protein (LRP) is a multifunctional cell
      surface receptor binding many different ligands including proteinases and their
      inhibitors, some of which are known to be involved in tumor biology. We studied
      the expression of LRP and its putative role in colorectal carcinoma. Tissue
      samples were obtained from 50 patients with colorectal carcinoma and fixed in
      formalin and embedded in paraffin. Immunohistochemical staining was performed
      using antibodies directed against LRP, cathepsin B and urokinase-type plasminogen
      activator (u-PA). The expression of LRP was further studied by polymerase chain
      reaction. The TNM stage was determined according to UICC guide lines and was
      based upon histological analysis. LRP was primarily expressed in stroma cells [36
      patients (72%)] and less frequently in tumor cells [6 patients (12%)]. In 22% of
      all cases LRP was prominent at the invasion front. Cathepsin B was found both in
      the tumor stroma [50 (100%)] and in the tumor cells [46 (92%)]. u-PA was present
      in the tumor stroma [44 (88%)] and in the tumor cells [44 (88%)]. In stromal
      cells the expression of LRP correlated significantly with the expression of u-PA
      (p=0.043). Furthermore, the expression of LRP and of u-PA in tumor cells
      correlated with the tumor stage according to UICC (p=0.038 and 0.018,
      respectively). We provide evidence that LRP is expressed in colorectal cancer. As
      LRP forms complexes with u-PA and its inhibitor, we suspect that LRP can
      influence the known effects of u-PA on tumor biology.

PMID- 17203176
TI  - Distinct roles of VEGF-A and VEGF-C in tumour metastasis of gastric carcinoma.
AB  - The expression of VEGF-A and -C was investigated immunohistochemically in 51
      specimens of gastric carcinoma. The expression intensity was evaluated by means
      of a semi-quantitative scoring system and a quantitative analysis. The results
      showed that VEGF-A and -C were located mainly in the cytoplasm of tumour cells:
      68.6% (34/51) and 62.8% (32/51) positive for VEGF-A and VEGF-C. VEGF-C expression
      was more frequent in tumours of the deceased patients [88.2% (15/17)] compared to
      that in the survivors [47.0% (16/34)]. Quantitative VEGF-C levels in the deceased
      patients were 0.304+/-0.023, which was significantly elevated compared to that in
      the survivors (0.131+/-0.018) (p<0.01). The frequency of VEGF-C expression was
      higher in patients with lymph node metastases (80.0%, 28/35) compared to those
      with negative nodes (25%, 4/16). Accordingly, its levels were markedly elevated
      in the former (0.230+/-0.017) than in the latter (0.089+/-0.011) (p<0.01).
      Furthermore, tumour cell invasion into the enlarged lymphatic vessels was also
      associated with VEGF-C expression. Its expression levels were 0.271+/-0.028 in
      lymph vessel invasion and 0.153+/-0.021 in the absence of invasion (p<0.01). VEGF
      A expression, although correlated with survival, distant metastasis, ascites
      formation, and blood vessel invasion, was not associate with lymph node
      metastasis, lymphatic vessel invasion. The expression levels of the two factors
      were inversely correlated with overall survival rates. It can be conclude that
      VEGF-C expression in tumour tissues is indicative of lymphatic metastasis,
      whereas VEGF-A expression is more likely to be associated with haematogenous
      metastasis. Both VEGF-A and -C could serve as a prognostic biomarker in patients
      with gastric carcinoma.

PMID- 17203177
TI  - Apoptosis induced by lycorine in KM3 cells is associated with the G0/G1 cell
      cycle arrest.
AB  - Lycorine is a natural anti-tumor alkaloid extracted from Amaryllidaceae and has
      various biological effects on malignant cells. The present study explores the
      effects of lycorine on the human multiple meyloma cell line, KM3, and the
      possible mechanisms of these effects. An MTT assay showed that lycorine had
      significant inhibitory activity on KM3 cells. The growth rates of the KM3 cells
      exposed to lycorine evidently slowed down. Cell fluorescent apoptotic
      morphological changes, DNA degradation fragments, and a sub-G1 peak were
      detected, indicating the occurrence of cell apoptosis after lycorine treatment.
      Furthermore, the release of mitochondrial cytochrome c, the augmentation of Bax
      with the attenuation of Bcl-2, and the activation of caspase-9, -8, and -3 were
      also detected, suggesting that the mitochondrial pathway and the death acceptor
      pathway were also involved. The results also showed that lycorine was able to
      block the cell cycle at the G0/G1 phase through the downregulation of both cyclin
      D1 and CDK4. In summary, lycorine can suppress the proliferation of KM3 cells and
      reduce cell survival by arresting cell cycle progression as well as inducing cell
      apoptosis.

PMID- 17203178
TI  - The effect of chemotherapy on status of estrogen receptors in primary tumors and
      lymph node metastases of human ductal breast cancer.
AB  - The aim of the study was the evaluation of ERalpha and ERbeta expression in
      primary tumors and lymph node metastases of breast cancer as well as the
      assessment of the influence of preoperative chemotherapy on these receptors with
      regard to changes in morphological appearance of primary tumors and their
      metastases. Immunohistochemical examinations were conducted on surgically removed
      ductal invasive breast cancers and their lymph node metastases of 135 patients.
      Seventy-one patients were spared preoperative chemotherapy which was administered
      to other 64 patients. Primary breast cancers with preoperative chemotherapy
      showed lower mean percentage of cells with a positive reaction to ERalpha and
      ERbeta as compared to primary tumors without preoperative chemotherapy. There
      were positive correlations among primary tumors and lymph node metastases
      regardless of preoperative chemotherapy applied. On the other hand, ERalpha and
      ERbeta expressions were negatively correlated in primary tumors without
      chemotherapy in contrast to primary tumors after chemotherapy. Furthermore, it
      was observed that preoperative chemotherapy was responsible for significantly
      less damage to lymph node metastases of breast cancer in comparison to primary
      tumors. In cases of such advanced damage of primary tumors that made
      determination of estrogen receptor expression impossible, their evaluation was
      performed on metastases to regional lymph nodes. Although preoperative
      chemotherapy did not severely impair estrogen receptor expression, presented
      changes of their distribution are a sufficient reason for simultaneous labeling
      of estrogen receptors in both primary tumors and metastases due to various
      sensitivity to chemotherapy of primary cancers in comparison with involved lymph
      nodes.

PMID- 17203180
TI  - Expression analysis of pancreatic cancer cell lines reveals association of
      enhanced gene transcription and genomic amplifications at the 8q22.1 and 8q24.22
      loci.
AB  - Despite tremendous effort and progress in the diagnostics of pancreatic cancer
      with respect to imaging techniques and molecular genetics, only very few patients
      can be cured by surgery leading to a 5-year survival rate of only 3%. Especially
      the lack of chemotherapeutical options in this entity requires a better
      understanding of the molecular mechanisms leading to pancreatic carcinoma growth
      and progression in order to develop novel treatment regimens. To identify
      signaling pathways that are critical for this tumor entity, we compared six well
      established pancreatic cancer cell lines (Capan-1, Capan-2, HUP-T3, HUP-T4, KCL
      MOH, PaTu-8903) with colon cancer cell lines and tumor cell lines of non
      epithelial origin by expression profiling. For this purpose we employed Human
      Genome Focus Arrays representing about 8500 well annotated human genes. We
      identified 353 genes with significantly high expression in the group of
      pancreatic carcinomas. Based on Gene Ontology annotations these genes are
      especially involved in Rho protein signal transduction, proteasome activator
      activity, cell motility, apoptotic program, and cell-cell adhesion processes
      indicating these pathways to be interesting candidates for the design of targeted
      therapies. Most pancreatic carcinomas are characterized by mutations in the TP53
      and the KRAS genes and the absence of microsatellite instability, which could
      also be confirmed for our panel of pancreatic carcinoma cell lines. Looking for
      individual differences within this group that may be responsible for more or less
      aggressive behavior, we identified genomic amplifications at the 8q22.1 and the
      8q24.22 loci to be associated with enhanced gene transcription. Because we have
      previously shown that gains of genomic material from the long arm of chromosome 8
      have an adverse effect on the outcome of pancreatic carcinoma patients, we
      conclude that functional analysis of amplified genes at 8q22 and/or 8q24 may lead
      to an improved understanding of pancreatic carcinoma progression.

PMID- 17203179
TI  - Expression of maspin in endometrioid adenocarcinoma of endometrium.
AB  - Maspin is a member of the serpin family, whose expression is altered in neoplasia
      and malignancies of many tissues. Underexpression of maspin has been reported in
      breast and prostatic cancers, but in some cancers such as ovarian, colorectal and
      pancreatic carcinoma, it was found to be up-regulated. This study aimed at
      demonstrating the expression of maspin in human endometrial tissue and searching
      for any altered expression in endometrioid adenocarcinoma of the endometrium
      compared to normal endometrium. The expression level of the maspin gene was
      studied using reverse transcriptase-polymerase chain reaction (RT-PCR) performed
      on RNA extracted from 34 endometrial cancer samples (including 24 with FIGO stage
      I disease and 10 with FIGO stage III disease) and 28 normal endometrium in
      proliferative or secretory phases. Immunohistochemical staining was also
      performed on 10 cases of endometrial cancer (6 FIGO stage I cases and 4 FIGO
      stage III cases) as well as 15 normal endometrium. Semi-quantitative RT-PCR
      revealed that the expression of maspin was significantly up-regulated in both
      stage I (p<0.01) and stage III (p<0.01) endometrial cancer compared with normal
      endometrium. However, no significant difference in maspin expression was
      demonstrated between stage I and stage III endometrial cancer. Immunostaining of
      all tissue sections revealed an immunopositive signal in the nuclei of the normal
      or cancerous endometrial glandular cells. In 60% of the cancer cases, cytoplasmic
      staining was also evident. Our results suggested that there is up-regulated
      expression of maspin in endometrioid endometrial adenocarcinoma. Cytoplasmic
      immuno-expression of maspin is common in endometrial cancer. It may play a role
      in the malignant transformation of human endometrial tissue.

PMID- 17203181
TI  - Caspase-independent cell death revealed in human gastric cancer cell lines, MKN45
      and KATO III treated with phenoxazine derivatives.
AB  - We examined whether phenoxazine derivatives such as 2-amino-4,4alpha-dihydro
      4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1) and 2-aminophenoxazine-3-one (Phx
      3) may have anticancer effects on the human gastric cancer cell lines, MKN45,
      MKN74, MKN7 and KATO III in vitro. Phx-1 inhibited the growth of these cancer
      cells in a dose- and time-dependent manner. The IC50 was approximately 65, 25,
      100 and 70 microM for MKN45, MKN74, MKN7 and KATO III respectively, after 72 h.
      Phx-3 exerted stronger antiproliferative effects against these cancer cells
      (IC50: approximately 5, 1, 10 and 10 microM for MKN45, MKN74, MKN7 and KATO III,
      respectively, after 72 h) than Phx-1. Phx-1 and Phx-3 increased the population of
      TUNEL-positive cells in MKN45 and KATO III time-dependently from 24 to 72 h,
      suggesting that Phx-1 and Phx-3 have apoptotic activity against these gastric
      cancer cells. The activity of effector caspase-3 significantly increased in MKN45
      treated with Phx-3 for 24 h, but did not altered in the cells treated with Phx-1
      for 24 h. When z-VAD-fmk, a pan-caspase inhibitor, was co-treated for 24 h, Phx-3
      stimulated caspase-3 activity in MKN45 was reversed to the levels of normal
      activity, while the antiproliferative and apoptotic effects of Phx-3 against the
      cells were maintained. The activity of caspase-3 was not activated in KATO III by
      24 h exposure for Phx-1 or Phx-3. In conclusion, both phenoxazines prevent the
      growth of the human gastric cancer cell lines, MKN45 and KATO III in vitro, and
      cause the apoptosis of these cell lines via a caspase-independent pathway.
      Although the intracellular action mechanisms of Phx-1 and Phx-3 are still
      unclear, these phenoxazines may be useful for the treatment of gastric cancer in
      the future.

PMID- 17203182
TI  - Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the
      plasminogen activator/plasmin system, leading to suppression of progression of
      oral squamous cell carcinoma via upregulation of cell-cell adhesion.
AB  - The plasminogen activator/plasmin system is one of the main protease systems
      involved in tumor cell invasion and metastasis. Our previous study has shown that
      plasmin degrades E-cadherin and promotes cell dissemination by downregulation of
      E-cadherin-mediated cell-cell adhesion in oral squamous cell carcinoma (SCC)
      cells. To examine the effect of downregulation of the plasminogen
      activator/plasmin system by alpha2-antiplasmin (alpha2-AP) on cell-cell adhesion
      mediated by E-cadherin in oral SCC cells, the oral SCC cell line SCCKN was stably
      transfected with alpha2-AP cDNA. Induction of alpha2-AP expression led to the
      inhibition of the proteolysis of E-cadherin by plasminogen activator/plasmin in
      SCC cells, resulting in the enhancement of the cell aggregation and the
      suppression of the cell motility. Moreover, alpha2-AP also reduced the ability of
      SCC cells to invade type I collagen gel, and suppressed tumorigenicity in vivo.
      These results suggested that downregulation of the plasminogen activator/ plasmin
      system by alpha2-AP might be a potent therapeutic approach to prevent the
      progression of oral SCC.

PMID- 17203183
TI  - Ethyl acetate extract of Chinese medicinal herb Sarcandra glabra induces growth
      inhibition on human leukemic HL-60 cells, associated with cell cycle arrest and
      up-regulation of pro-apoptotic Bax/Bcl-2 ratio.
AB  - Sarcandra glabra (Thunb.) Nakai, colloquially known as Caoshanhu, is a Chinese
      medicinal herb with reported anti-tumor, anti-inflammatory, anti-viral and non
      specific immunoenhancing properties. Although the plant has been clinically used
      for treating a variety of diseases, its bioactive ingredients are largely unknown
      and its mode of action has never been investigated. In this study, the anti-tumor
      property of ethyl acetate (EA) extract of S. glabra was investigated by
      determining its in vitro growth-inhibitory effects on a panel of human cancer
      cell lines of different histotypes. Growth inhibition of the EA extract on the
      cancer cells seemed to be selective, and the leukemic HL-60 was found to be the
      most responsive after 48 h of treatment (IC50=58 microg/ml). Flow cytometric
      studies further illustrated that the extract might interfere with DNA replication
      and thus arrested the cell cycle at S phase in the leukemic cells, followed by
      DNA fragmentation and loss of phospholipid asymmetry in the plasma membrane after
      72 h of treatment. Concurrently, the pro-apoptotic Bax/Bcl-2 ratio was also up
      regulated by more than 178% of the control level. All these findings suggested
      that the extract had initiated apoptosis to kill the leukemic cells. Results from
      this pioneer study help to establish a scientific foundation for future research
      and development of the bioactive ingredients in EA extract of S. glabra as
      efficacious anti-cancer agents.

PMID- 17203184
TI  - Edelfosine protects precultured heart fragments against the invasion of malignant
      cells through altered sialylation.
AB  - 1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OMe)-treated precultured
      heart fragments (PHF) are resistant to the invasion of malignant cells. Previous
      studies have demonstrated that this effect is due to the alterations of the N
      linked glycoproteins in PHF after 48-h ET-18-OMe treatment. Moreover, the
      observed effect was still present seven days after ET-18-OMe was omitted. The
      present study reveals that approximately 13.4% of the administered ET-18-OMe was
      taken up by PHF and about 75% of the initial uptake was still present after ET-18
      OMe was removed. In addition, we found significant changes in the sialic acid
      content and sialyltransferase activities in both conditions. Overall, these
      results clearly demonstrate that the uptake and retention of ET-18-OMe are
      responsible for the resistance to the invasion of malignant cells due to the
      altered sialylation of the cell surface glycoproteins in PHF.

PMID- 17203185
TI  - Synergistic inhibition of hepatocellular carcinoma growth and
      hepatocarcinogenesis by combination of 5-fluorouracil and angiotensin-converting
      enzyme inhibitor via anti-angiogenic activities.
AB  - Therapies aimed at destruction of the tumor vasculature are now recognized as a
      promising approach against cancer, and it has been reported that the combination
      treatment with an angiogenic inhibitor and conventional chemotherapeutic drug
      exerted synergistic anti-cancerous effects. We previously reported that the
      clinically used angiotensin-converting enzyme inhibitor (ACE-I) exerted potent
      anti-angiogenic activities. The aim of our current study was to examine the
      combined effect of ACE-I and 5-fluorouracil (5-FU), which is widely used for
      hepatogastrointestinal tumors, on hepatocellular carcinoma (HCC) growth and
      hepatocarcinogenesis. When used individually at low doses, neither 5-FU nor ACE-I
      exerted significant inhibitory effects on the HCC growth. However, the
      combination treatment of 5-FU and ACE-I showed a potent inhibitory effect on HCC
      growth along with suppression of neovascularization in the tumor. The expression
      level of the vascular endothelial growth factor, a potent angiogenic factor, was
      also suppressed, almost in conjunction with tumor growth inhibition. Furthermore,
      5-FU and ACE-I treatment resulted in a marked increase of apoptosis in the tumor.
      In the hepatocarcinogenesis model, the combination treatment with 5-FU and ACE-I
      also showed a marked inhibitory effect on the development of preneoplastic
      lesions. The in vitro study demonstrated that this combination treatment
      inhibited endothelial cell tubular formation. Collectively, the combination
      treatment of 5-FU and ACE-I exerted a marked synergistic inhibitory effect on HCC
      growth via suppression of angiogenesis. This regimen also showed a
      chemopreventive effect against hepatocarcinogenesis. Since both 5-FU and ACE-I
      are widely used in clinical practice, this combination therapy may be an
      effective new therapeutic strategy against HCC in the future.

PMID- 17203186
TI  - Beta-catenin expression in relation to genetic instability and prognosis in
      colorectal cancer.
AB  - In the carcinogenesis of colorectal cancer (CRC) genetic instability and
      dysfunction of the Wnt-signalling pathway play important roles. Most Wnt
      signalling dysfunctions lead to the nuclear accumulation of beta-catenin. The aim
      of the present study was to investigate whether nuclear accumulation of beta
      catenin is associated with prognosis and genetic instability. We used
      immunohistochemistry to study nuclear beta-catenin expression in 67 CRCs. The
      expression was evaluated in the entire tumour section as mean values and in
      tumour budding at the invasive margin. We compared the results with chromosomal
      and microsatellite instability (CIN vs. MSI), p53 accumulation, and
      clinicopathological variables including survival. The nuclear accumulation of
      beta-catenin was significantly associated with abnormal p53 expression and
      aneuploidy, typically for CIN, whereas no tumour with nuclear beta-catenin
      expression at the invasive margin displayed MSI. The beta-catenin expression
      pattern did not correlate significantly with CRC patient prognosis when including
      all stages. However, in the clinically most interesting prognostic group, Dukes'
      stage B patients, high nuclear accumulation of beta-catenin was associated with a
      poor prognosis (p=0.01). Our results suggest that nuclear accumulation of beta
      catenin in CRC is related to CIN and may be of prognostic importance. However,
      larger studies are needed to verify these findings.

PMID- 17203187
TI  - Context of MUC1 epitope: immunogenicity.
AB  - MUC1 is a glycoprotein found at the secretory poles of normal cells but is
      hypoglycosylated on the entire surface of cell membranes of adenocarcinomas. In
      order to determine the influence on the immune response of peptide context for
      epitope presentation, peripheral blood mononuclear cells (PBMC) from patients
      with adenocarcinomas, were stimulated with MUC1 peptides derived from the 20
      amino acids (aa) long sequence that is characteristic of the MUC1 Variable Number
      of Tandem Repeats (VNTR). In the seven peptides tested, the T-cell tumor-specific
      epitope (cTSE) was surrounded by variable numbers of aa and repeated up to 5
      times in the same peptide. The results of this study indicate that cultures
      stimulated with peptide 610 (GSTAPPAHGVTS APDTRPAP) showed the highest specific
      killing of the MUC1-expressing breast cancer MCF-7 cells. Peptide 610 is also
      superior to the other peptides in inducing better production of the type 1
      cytokines, tissue necrosis factor alpha and interferon gamma. In conclusion,
      context of the epitope and not sequence alone determines immunogenicity.

PMID- 17203188
TI  - Screening of genomic imbalances in glioblastoma multiforme using high-resolution
      comparative genomic hybridization.
AB  - Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that
      allows the genome-wide analysis of DNA sequence copy number differences. We
      applied conventional CGH and the recently developed high-resolution CGH (HR-CGH)
      to tumour samples from 18 patients with glioblastoma multiforme (GBM) in order to
      compare the sensitivity of CGH and HR-CGH in the screening of chromosomal
      abnormalities. The abnormalities were studied in topologically different central
      and peripheral tumour parts. A total of 78 different changes were observed using
      CGH (0-16 per tumour, median 3.5) and 154 using HR-CGH (0-21 per tumour, median
      6). Using HR-CGH, losses were more frequent than gains. The representation of the
      most prominent changes revealed by both methods was similar and was comprised of
      the amplification of 7q12 and 12q13-q15, the gain of 7, 3q and 19, and the loss
      of 10, 9p, and 13q. However, HR-CGH detected certain other abnormalities (the
      loss of 6, 14q, 15q and 18q, and the gain of 19), which were rarely revealed by
      CGH. Using HR-CGH, the numbers and types of chromosomal changes detected in the
      central and peripheral parts of GBM were almost the same. The loss of chromosomes
      10 and 9p and the gain of chromosomes 7 and 19 were the most frequent chromosomal
      alterations in both tumour parts. Our results from the GBM analysis show that HR
      CGH technology can reveal new, recurrent genetic alterations involving the genes
      known to participate in tumorigenesis and in the progression of several human
      malignancies, thus allowing for a more accurate genetic characterization of these
      tumours.

PMID- 17203189
TI  - Synergistic inhibition of breast cancer cell lines with a dual inhibitor of EGFR
      HER-2/neu and a Bcl-2 inhibitor.
AB  - The epidermal growth factor receptor (EGFR) (ErbB1) and HER-2/neu (ErbB2) are
      members of the ErbB family of receptor tyrosine kinases. These receptors are
      overexpressed in a variety of human tumors and overexpression generally
      correlates with poor prognosis and decreased survival. Lapatinib, a reversible
      inhibitor of both EGFR and HER-2/neu, has shown some success in achieving
      clinical responses in heavily pretreated advanced cancer patients. GW2974 is a
      reversible dual inhibitor similar to lapatinib, but GW2974 was not progressed to
      clinical trials due to pharmacokinetic issues. Bcl-2, an anti-apoptotic protein,
      is also overexpressed in a number of human tumors. Bcl-2 inhibitors induce
      apoptosis and sensitize cancer cells to other therapies. The purpose of this
      study was to assess the effects of combining ErbB and Bcl-2 inhibitors on the
      growth of human breast cancer cell lines. EGFR/HER-2/neu tyrosine kinase
      inhibitors (lapatinib and GW2974) were combined with Bcl-2 inhibitors (HA14-1 or
      GX15-070) and the anti-proliferative effects were determined by the MTT
      tetrazolium dye assay. Combinations were tested in MCF-7 human breast cancer
      cells, a HER-2/neu transfected MCF-7 cell line (MCF/18), and a tamoxifen
      resistant MCF-7 cell line (MTR-3). A synergistic inhibitory effect was observed
      with the combination of inhibitors of EGFR-HER-2/neu (lapatinib or GW2974) and
      Bcl-2 (GX15-070 or HA14-1) on the growth of the MCF-7, MCF/18, and MTR-3 human
      breast cancer cell lines. This study suggests that simultaneously blocking the
      ErbB family of receptor tyrosine kinases and Bcl-2 family of proteins may be a
      benefit to breast cancer patients.

PMID- 17203190
TI  - Clinical factors in prediction of prognosis after anterior resection with total
      mesorectal excision for carcinoma of the rectum.
AB  - The aim of the study was to estimate the long-term results and the prognostic
      value of clinical and pathological factors following R0 anterior resection with
      total mesorectal excision (TME). Ninety-eight consecutive patients with
      histologically confirmed rectal cancer were studied prospectively with five-year
      follow-up. Survival was calculated using the Kaplan-Meier method and differences
      between curves were tested by the log-rank test. Multivariate analysis was
      performed using the Cox regression model. Recurrence-free survival (RFS) was
      63.6%. Mean time of recurrence was 13.8 months (range 3-38). Local recurrence
      rate was 7.8% with the mean time of 12.7 months (range 3-25). In univariate
      analysis Dukes' stage (RFS for stage: A=93.2%; B=53.8%; C=26.3%) and preoperative
      CEA serum level (s-CEA) (for s-CEA<or=5 ng/ml RFS=93.8%; for s-CEA>5 ng/ml
      RFS=5.9%) significantly influenced survival (P<0.005 and P<0.00001). These
      parameters were also found to be independent prognostic factors in multivariate
      analysis (P<0.05 and P<0.00001). Survival was worse in older female patients with
      low-localised poorly differentiated tumors; however, those variables had not
      significant impact on prognosis. Neither symptom duration nor mucinous histology
      was significantly related to survival. Using TME technique a low local recurrence
      rate resulting in improved survival can be achieved. Apart from
      clinicopathological staging, elevated s-CEA can identify patients with poor
      prognosis. In addition to TME adjuvant therapy for this high-risk group should be
      considered.

PMID- 17203191
TI  - ATM gene mutations in former uranium miners of SDAG Wismut: a pilot study.
AB  - Ataxia-telangiectasia is an autosomal recessive disease characterized by
      neurological and immunological symptoms, radiosensitivity and cancer
      predisposition. Heterozygous carriers of an ataxia-telangiectasia gene mutation
      are predisposed to epithelial cancers. We initiated a study to elucidate the
      frequency and clinical relevance of ATM gene mutations in former uranium miners
      exposed to high levels of radiation from radon and its decay products. Former
      uranium miners with Schneeberg lung cancer (n=48), former uranium miners
      suffering from silicosis (n=60) and uranium miners without occupational lung
      disorders (n=102) were investigated for nine mutations in the ATM gene. One
      gastric and one prostate cancer occurred in the group of miners without
      occupational lung diseases. Mutation analyses for S707P, IVS10-6Tright curved
      arrow G, 2250Gright curved arrow A, E1978X, R2443X, 3801delG, S49C and D2625E
      A2626P were performed using genomic DNA obtained from peripheral blood samples.
      Three ATM gene alterations (S707P, S49C or IVS10-6Tright curved arrow G) were
      observed. Of all cancer patients, 8.0% were heterozygous, but only 1.9% of the
      non-cancer controls were [OR=4.6; 95% confidence interval (CI), 0.8-26.8]. In
      this pilot study a major role of six ATM gene mutations could not be revealed for
      cancer predisposition in former uranium miners. The results leave the possibility
      of a moderate risk associated with more subtle ATM gene alterations.

PMID- 17203192
TI  - Relationship between COPD and polymorphisms of HOX-1 and mEPH in a Chinese
      population.
AB  - Recent studies have proposed that susceptibility to chronic obstructive pulmonary
      disease (COPD) might be related with the polymorphisms of some genes encoding
      antioxidant enzymes, such as heme oxygenase-1 (HOX-1) and microsomal epoxide
      hydrolase (mEPH). We examined these polymorphisms in 256 patients with COPD and
      266 healthy smokers from Han population in Southwest China. The frequencies of
      each allele were compared both individually and in combination between patients
      and controls. Polymorphisms of HOX-1 gene could be grouped into three classes: S
      (<or=25 repeat), M (26-31 repeat), and L (>or=32 repeat). The allele frequencies
      of class L and the genotypic frequencies of the group with L were significantly
      higher in COPD than in controls. Our findings also showed that the proportion of
      slow mEPH activity was significantly higher in COPD than in controls. Conversely,
      the proportion of fast mEPH activity was significantly lower in COPD. In combined
      analysis, the frequency of the individuals having at least one L allele in the
      HOX-1 gene promoter and slow or very slow activity genotype for mEPH was higher
      in COPD than in control. Genetic polymorphisms in HOX-1 and mEPH genes are
      associated with the development of COPD in Southwest China.

PMID- 17203194
TI  - Genistein and zinc synergistically enhance gene expression and mineralization in
      osteoblastic MC3T3-E1 cells.
AB  - Genistein, a phytoestrogen, and zinc, an essential trace element, have an
      anabolic effect on bone components. We investigated whether the combination of
      genistein and zinc has additive and synergistic effects in osteoblastic cells in
      vitro. Osteoblastic MC3T3-E1 cells with subconfluency were cultured for 48 h in
      medium containing either vehicle, genistein (10(-6) or 10(-5) M), zinc sulfate
      (10(-5) or 10(-4) M) or genistein (10(-6) or 10(-5) M) plus zinc sulfate (10(-5)
      or 10(-4) M). The protein content in the osteoblastic cells was significantly
      increased in the presence of genistein (10(-5) M) or zinc (10(-4) M). This
      increase was significantly enhanced with a culture of genistein (10(-5) M) plus
      zinc (10(-4) M). The expression of mRNAs of alpha1(I) collagen and osteocalcin,
      which are bone matrix protein, in osteoblastic cells was demonstrated using
      reverse transcription-polymerase chain reaction (RT-PCR) analysis with a specific
      primer. This expression was not significantly increased with genistein (10(-6) or
      10(-5) M) or zinc (10(-5) or 10(-4) M). The combination of genistein (10(-6) or
      10(-5) M) and zinc (10(-5) or 10(-4) M) caused a significant increase in
      alpha1(I) collagen and osteocalcin mRNA expression in osteoblastic cells.
      Alkaline phosphatase mRNA expression in osteoblastic cells was significantly
      enhanced with a culture of genistein (10(-5) M) plus zinc (10(-4) M). The effect
      of genistein (10(-5) M) plus zinc (10(-4) M) in enhancing the expression of
      alpha1(I) collagen, alkaline phosphatase, or osteocalcin mRNAs in osteoblastic
      cells was completely prevented with a culture of cycloheximide (10(-7) M), an
      inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D
      ribofuranosylbenimidazole (DRB) (10(-6) M), an inhibitor of transcriptional
      activity. Moreover, a culture with genistein (10(-5) M) or zinc (10(-4) M) for 14
      or 21 days caused a significant increase in mineralization. This increase was
      markedly enhanced with a culture of the combination of genistein (10(-5) M) and
      zinc (10(-4) M). This study demonstrates that the combination of genistein and
      zinc can synergistically enhance gene expression and mineralization in
      osteoblastic cells.

PMID- 17203193
TI  - Effects of neuropeptides B and W on the rat pituitary-adrenocortical axis: in
      vivo and in vitro studies.
AB  - Neuropeptides (NP) B and W are hypothalamic peptides involved in the regulation
      of feeding and neuro-endocrine axes. Evidence has been provided that NPB and NPW
      act on both the central and the peripheral branches of the rat hypothalamic
      pituitary-adrenocortical axis, and we carried out in vivo and in vitro studies to
      gain insight into this topic. Reverse transcription-polymerase chain reaction
      showed the expression of NPB, NPW and their receptors in both adrenal cortex
      (zonae glomerulosa and fasciculata-reticularis) and adrenal medulla, where
      immunocytochemistry also detected the presence of abundant NPB- and NPW
      immunoreactivity. The acute subcutaneous administration of NPB (0.5 or 1.5
      nmol/100 g) did not alter ACTH plasma concentration, while that of NPW (1.5
      nmol/100 g) decreased it. Neither NPB nor NPW affected the blood level of
      aldosterone, while both peptides (0.5 nmol/100 g) raised that of corticosterone.
      NPB (10(-6) M) lowered ACTH-stimulated aldosterone secretion, and basal and ACTH
      stimulated corticosterone production from adrenal quarters containing both
      cortical and medullary tissues. NPW (10(-6) M) enhanced basal aldosterone
      secretion from adrenal quarters, and the effect was suppressed by the beta
      adrenoceptor antagonist l-alprenolol (10(-5) M). NPW did not affect
      corticosterone production. Collectively, our findings allow us to draw the
      following tentative conclusions: i) ACTH-independent extra-adrenal mechanism(s)
      are operative in vivo, by which NPB and NPW stimulate adrenal glucocorticoid, but
      not mineralocorticoid secretion; ii) in vitro the interaction of NPB with adrenal
      medulla activates unknown mechanism(s) hampering adrenocortical steroidogenic
      machinery; and iii) NPW stimulates in vitro aldosterone secretion by enhancing
      the release of medullary catecholamines, which in turn activate beta
      adrenoceptors located on zona glomerulosa cells.

PMID- 17203195
TI  - Depletion of endothelial progenitor cells in the peripheral blood of patients
      with ulcerative colitis.
AB  - There is strong evidence to suggest that endothelial progenitor cells (EPCs) play
      a significant role in re-endothelialization and subsequent tissue repair. This
      study examined the role of EPCs in inflammatory bowel disease, a disease in which
      impairment of mucosal healing has been implicated. Peripheral blood mononuclear
      cells obtained from 50 patients with ulcerative colitis (UC), 29 patients with
      Crohn's disease (CD), 14 patients with infectious colitis, and 35 normal control
      subjects were cultured in EPC medium, harvested after 7 days, and characterized
      by immunocytochemistry and flow cytometry. Colony assay for hematopoietic
      progenitor cells was also performed. Patients with active UC had a significantly
      decreased number of circulating EPCs as compared with healthy controls
      (p=0.0013), patients with inactive UC (p=0.0099), patients with active CD
      (p=0.0235) and patients with infectious colitis (p=0.0002). On the other hand,
      patients with infectious colitis had a significantly increased number of
      circulating EPCs as compared with healthy controls (p=0.0406), patients with
      active UC (p=0.0002), and patients with active CD (p=0.0316). In patients with
      UC, the number of circulating EPCs was correlated with the serum hemoglobin
      levels (r=0.485, p=0.007) and inversely with the platelet count (r=-0.372,
      p=0.0382). The number of hematopoietic progenitor cell colonies was comparable
      among patients with UC, patients with CD, patients with infectious colitis, and
      healthy controls. Our observations indicate that the number of circulating EPCs
      in patients with UC is significantly reduced. Further studies are needed to
      define the mechanisms that underlie the reduction in the number of circulating
      EPCs and to better understand the pathophysiological consequences of this event
      in patients with UC.

PMID- 17203196
TI  - The nitric oxide donor LA 419 decreases ischemic brain damage.
AB  - Stroke represents a major clinical problem with limited available therapeutic
      treatments. Nitric oxide (NO) and the enzymes that produce it are involved in the
      pathogenesis of this disease. Here we investigated whether the novel NO donor LA
      419 was able to ameliorate the consequences of stroke in an experimental model of
      global ischemia. We observed a sharp increase in the amounts of inducible NO
      synthase (iNOS) and nitrotyrosine in the cerebral cortex of experimental rats and
      a moderate increase of neuronal NO synthase (nNOS), as demonstrated by
      immunohistochemistry, Western blotting, and enzymatic activity assays. Treatment
      of these animals with LA 419 completely prevented ischemia-induced upregulation
      of nitrergic markers. Magnetic resonance imaging of the experimental brains
      showed a marked decrease in apparent diffusion coefficient (ADC) following
      ischemia-reperfusion, which was significantly corrected by pre-treatment with LA
      419. These results clearly show that LA 419 is an efficient modulator of NO
      related pathophysiological events and could eventually be used for the treatment
      of patients with cerebrovascular pathologies.

PMID- 17203197
TI  - A neutrophil elastase inhibitor, sivelestat, ameliorates lung injury after
      hemorrhagic shock in rats.
AB  - Hemorrhagic shock followed by resuscitation (HSR) causes neutrophil sequestration
      in the lung which leads to acute lung injury (ALI). Neutrophil elastase (NE) is
      thought to play a pivotal role in the pathogenesis of ALI. This study
      investigated whether sivelestat, a specific NE inhibitor, can attenuate ALI
      induced by HSR in rats. Male Sprague-Dawley rats were subjected to hemorrhagic
      shock by withdrawing blood so as to maintain a mean arterial blood pressure of
      30+/-5 mm Hg for 60 min followed by resuscitation with the shed blood. HSR
      treated animals received a bolus injection of sivelestat (10 mg/kg) intravenously
      at the start of resuscitation followed by continuous infusion for 60 min (10
      mg/kg/h) during the resuscitation phase, or the vehicle. Lung injury was assessed
      by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio,
      myeloperoxidase (MPO) activity, gene expression of tumor necrosis factor (TNF)
      alpha and inducible nitric oxide synthase (iNOS), DNA binding activity of nuclear
      factor (NF)-kappaB, and immunohistochemical analysis of intercellular adhesion
      molecule (ICAM)-1. HSR treatment induced lung injury, as demonstrated by
      pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio,
      MPO activity, gene expression of TNF-alpha and iNOS, and DNA-binding activity of
      NF-kappaB, and enhanced expression of ICAM-1. In contrast, sivelestat treatment
      significantly ameliorated the HSR-induced lung injury, as judged by the marked
      improvement in all these indices. These results indicate that sivelestat
      attenuated HSR-induced lung injury at least in part through an inhibition of the
      inflammatory signaling pathway, in addition to the direct inhibitory effect on
      NE.

PMID- 17203198
TI  - In vitro and in vivo characteristics of frozen/thawed neonatal pig split-skin
      strips: a novel biologically active dressing for areas of severe, acute or
      chronic skin loss.
AB  - The recurrent shortage of human skin autografts or allografts used to close
      extensive wounds has rekindled the search for feasible alternatives. In the past,
      adult pig skin was a popular biological dressing, yet doubts regarding its
      benefits have induced most people to abandon its use. Here we investigated the
      aptness of neonatal pig split-skin (NPSS) strips to be used as a novel kind of
      temporary dressing for areas of skin loss. NPSS strips are able to be prepared in
      bulk amounts, stored at -80 degrees C for up to six months, and recovered by
      swift thawing at 45 degrees C with no change in histological structure. When set
      into organ cultures in vitro for up to three weeks, these frozen/thawed NPSS
      strips exhibited both a skin-typical energy-linked metabolism (i.e., a
      predominant consumption of L-glutamine instead of glucose), and an enduring
      ability to secrete cytokines/chemokines such as IL-1alpha, IL-6, GM-CSF, and TNF
      alpha; all features alike in quantitative terms to those exhibited by freshly
      prepared NPSS strips directly set into culture. Moreover, once applied as
      temporary dressings onto deep burn wounds in vivo, frozen/thawed NPSS strips
      produced, for at least seven days, porcine IL-1alpha, IL-6, GM-CSF, TNF-alpha,
      and TGF-beta; the cytokines/chemokines importantly involved in wound healing.
      Hence, frozen/thawed NPSS strips not only are capable of closing extensive areas
      of skin loss, but even release several cytokines/chemokines beneficial to tissue
      regeneration and repair.

PMID- 17203199
TI  - Germinated barley foodstuff suppresses dextran sulfate experimental colitis in
      rats: the role of mast cells.
AB  - Recent studies have suggested that dietary fiber exerts a therapeutic effect on
      inflammatory bowel disease patients. The aim of this study was to evaluate the
      effects of a dietary fiber, germinated barley foodstuff (GBF), derived from the
      aleurone and scutellum fraction of germinated barley against dextran sulfate
      sodium (DSS)-induced experimental colitis in rats. Sprague-Dawley rats were fed a
      3% DSS diet containing GBF or alpha-cellulose for 8 days. The mucosal damage
      (macroscopic and microscopic inflammation) was then quantified. In addition, we
      evaluated the alterations in the mucosal mast cells and connective tissues. GBF
      effectively prevented mucosal damage. In addition, GBF suppressed the
      infiltration of the mucosal mast cells, and prevented the distraction of both
      collagen and elastic fibers. These effects may be closely associated with its
      inhibitory effects on mucosal mast cells, and the destruction of the mucosal
      connective tissues.

PMID- 17203201
TI  - STAT3-induced WNT5A signaling loop in embryonic stem cells, adult normal tissues,
      chronic persistent inflammation, rheumatoid arthritis and cancer (Review).
AB  - Leukemia inhibitory factor (LIF), oncostatin M, leptin, ciliary neurotrophic
      factor, cardiotrophin 1, cardiotrophin-like cytokine factor 1, interleukin 6
      (IL6), interleukin 11 and interleukin 27 activate the gp130-JAK-STAT3 signaling
      cascade. Here, WNT5A was characterized as the evolutionarily conserved target of
      the STAT3 signaling cascade based on 11-bp-spaced tandem STAT3-binding sites
      within intron 4 of human, chimpanzee, cow, mouse and rat WNT5A orthologs.
      Canonical WNT5A signaling through Frizzled and LRP5/LRP6 receptors activates
      FGF20, WISP1, MYC and CCND1 transcription for the maintenance of stem/progenitor
      cells, while non-canonical WNT5A signaling through Frizzled and ROR2/PTK7/RYK
      receptors activates the RHOA, JNK, NLK and NFAT signaling cascades for the
      control of tissue polarity, cell adhesion or movement. LIF-induced Wnt5a
      activates canonical Wnt signaling in mouse embryonic stem cells for self-renewal.
      STAT3-induced Wnt5a activates non-canonical Wnt signaling in rat cardiac myocytes
      for N-cadherin-dependent aggregation. IL6, secreted from epithelial cells or
      macrophages, induces WNT5A upregulation in mesenchymal cells. WNT5A then
      activates canonical WNT signaling in epithelial cells. IL6-induced WNT5A
      activates canonical WNT signaling for autocrine proliferation of human synovial
      fibroblasts in rheumatoid arthritis. IL-6 signaling is activated during human
      chronic atrophic gastritis with Helicobacter pylori infection, and aberrant Stat3
      signaling activation gives rise to mouse gastric tumors. WNT5A is frequently
      upregulated in human primary gastric cancer due to tumor-stromal interaction.
      WNT5A might be downregulated in advanced cancer with poorer prognosis due to
      genetic alterations compensating WNT5A signaling. Oncogenic WNT5A activates
      canonical WNT signaling in cancer stem cells for self-renewal, and non-canonical
      WNT signaling at the tumor-stromal interface for invasion and metastasis. SNP of
      genes encoding components of the cytokine-induced WNT5A signaling loop is a
      predicted risk factor for RA and cancer, especially diffuse-type gastric and
      pancreatic cancer. Humanized anti-IL6 receptor antibody and WNT5A mimetic small
      molecule antagonist could be applied to personalized medicine for RA and cancer
      driven by the IL6-induced WNT5A signaling loop.

PMID- 17203200
TI  - The pro-survival pathways of mTOR and protein kinase B target glycogen synthase
      kinase-3beta and nuclear factor-kappaB to foster endogenous microglial cell
      protection.
AB  - Microglia of the central nervous system serve a variety of functions that may
      ultimately lead to the development or detriment of neighboring neuronal and
      vascular cells. These scavengers of the nervous system have been associated with
      a variety of neurodegenerative disorders, but the toxic potential of microglia is
      equally balanced by the protective nature of these cells to exclude foreign
      microorganisms and promote new tissue proliferation and reorganization. To this
      extent, our work outlines a series of endogenous microglial cellular pathways
      that can constitute protection for microglia against during oxygen-glucose
      deprivation (OGD). We demonstrate in both primary microglia and the microglial
      cell line EOC 2 that endogenous microglial protection against OGD relies upon the
      activation and expression of the phosphatidylinositol 3-kinase pathways of
      mammalian target of rapamycin (mTOR) and protein kinase B (Akt1), since
      pharmacological inhibition of mTOR or Akt1 as well as the gene silencing of Akt1
      protein expression leads to significantly increased microglial apoptotic cell
      injury, DNA fragmentation, and membrane phosphatidylserine exposure. The mTOR
      pathway may offer endogenous protection through mechanisms that do not entirely
      rely upon inhibition of glycogen synthase kinase-3beta (GSK-3beta) activity while
      Akt1 appears to converge upon the necessary blockade of GSK-3beta. Closely
      aligned to these endogenous protective mechanisms is the subcellular presence and
      nuclear translocation of nuclear factor-kappaB p65 (NF-kappaB p65), since
      microglial cell injury is significantly increased during the gene silencing of NF
      kappaB p65. Elucidating the underlying pathways that can afford endogenous
      protection and maintain functional integrity of microglia should offer new
      prospects for the treatment of a broad range of nervous system disorders.

PMID- 17203202
TI  - Menaquinone-7 regulates gene expression in osteoblastic MC3T3E1 cells.
AB  - Previous study has shown that the vitamin K2 analog menaquinone-7 (MK-7) induces
      expression of the osteoblast-specific genes osteocalcin, osteoprotegerin,
      receptor activator of NFkappaB, and its ligand. Since MK-7 may also regulate
      osteoblast cell function, we examined the expression of osteoblast genes
      regulated by MK-7 administration. Differences between gene expression in control
      and MK-7-administered MC3T3E1 cells were analyzed using the suppression
      subtractive hybridization method. After 24 h of MK-7 administration, genes
      upregulated by MK-7 included tenascin C and BMP2. Genes downregulated by MK-7
      administration included biglycan and butyrophilin. Real-time PCR showed a marked
      increase in tenascin C. When the protein level was examined using Western blot
      analysis, tenascin C was higher in MK-7-administered cells than in control cells.
      These results indicated that MK-7 affected the cellular function of osteoblastic
      MC3T3E1 cells. Considering BMP2 mRNA expression was higher in MK-7-administered
      cells than in control cells, the effect of MK-7 administration on the signal
      transduction system was examined. Western blot analysis showed that cells
      administered MK-7 displayed a higher phosphorylated Smad1 level than control
      cells. Because MC3T3E1 cells have a nuclear binding receptor for MK-7, this
      result might indicate an indirect effect of MK-7 through BMP2 production.

PMID- 17203203
TI  - Labelling chemistry and characterization of [90Y/177Lu]-DOTA-ZHER2:342-3 Affibody
      molecule, a candidate agent for locoregional treatment of urinary bladder
      carcinoma.
AB  - The direct instillation of radiolabelled conjugates in the urinary bladder is a
      promising path for the treatment of bladder carcinoma. The targeting of HER2/neu
      receptors expressed on the surface of many bladder carcinoma cells shows
      potential to be developed as a therapeutic strategy, and patients identified with
      a high risk of progression may benefit from adjuvant targeted radionuclide
      therapy. A phage-display selected Affibody molecule (Z(HER2:342)) which binds to
      HER2/neu with picomolar affinity, can be used for targeting HER2/neu-expressing
      bladder carcinomas. A DOTA-derivative of Z(HER2:342), designated as DOTA
      Z(HER2:342)-3, is considered as a suitable targeting agent for therapy. The DOTA
      chelator provides stable labelling with radiometals, and the low molecular weight
      (7.2 kDa) of the DOTA-Z(HER2:342)-3 compound is expected to enable efficient
      tumor penetration. DOTA-Z(HER2:342)-3 was radiolabelled with 90Y and 177Lu in 1 M
      ammonium acetate buffer, at pH 5.5, and in the presence of ascorbic acid. Nearly
      quantitative labelling yields were achieved for both nuclides after 15 min of
      incubation at 60 degrees C. After chelation, the conjugates retained their
      capacity to specifically bind to HER2/neu-expressing SKOV-3 cells. The
      radiolabelled affibody conjugate (DOTA-Z(HER2:342)-3) demonstrated high antigen
      binding capacity and good cellular retention. Biodistribution in normal mice
      demonstrated low uptake in all organs and tissues except for kidneys.

PMID- 17203204
TI  - Genotype and variations in core promoter and pre-core regions are related to
      progression of disease in HBV-infected patients from Northern Vietnam.
AB  - Vietnam is one of the countries with a high rate of hepatitis B virus (HBV)
      infection, but there are only a few reports about relation of HBV genotypes and
      mutations to clinical course in Northern Vietnam. The characteristics of HBV and
      its relationship to clinical outcome in patients from Northern Vietnam were
      analyzed. Serum samples were collected from 183 HBV-infected Vietnamese patients.
      They were clinically categorized into 4 groups: hepatocellular carcinoma (HCC),
      liver cirrhosis (LC), chronic hepatitis (CH), and asymptomatic carriers (ASC).
      HBV serology, alpha-fetoprotein, HBV genotypes, HBV-DNA level and mutations in
      the core promoter and pre-core regions of HBV-DNA were examined. The majority of
      sera contained HBV genotype B (67.8%) and C (27.9%). The median age was matched
      between genotype B and C (38.2 vs. 42.9 years). The rates of HBeAg seroconversion
      and G1896A for genotype B were significantly higher than those for genotype C
      (P<0.05). Genotype C had a higher HBV-DNA level than genotype B. C1858 was
      frequent, especially in genotype C (62.7%). The most prevalent genotype in ASC
      and CH was genotype B. The presence of the mutation A1762T/G1764A correlated with
      disease progression. The triple mutation T1753C/A1762T/ G1764A was quite common
      and was more prevalent in LC and HCC than in CH and ASC. In Northern Vietnamese,
      HBV genotypes B and C were prevalent. Genotype C and mutations in the core
      promoter region were associated with progressive, severe liver diseases.

PMID- 17203205
TI  - Apicidin, a novel histone deacetylase inhibitor, has profound anti-growth
      activity in human endometrial and ovarian cancer cells.
AB  - Histone deacetylase inhibitors (HDACIs) can inhibit proliferation, induce cell
      cycle arrest and stimulate apoptosis of cancer cells. Our purpose was to
      investigate the antiproliferative effects of a novel HDACI, apicidin, on the
      Ishikawa endometrial cancer cell line, the SK-OV-3 ovarian cancer cell line and
      normal human endometrial epithelial cells. Endometrial and ovarian cancer cells
      were treated with various concentrations of apicidin, and the effects on cell
      growth, cell cycle, apoptosis and related measurements were investigated. MTT
      assays showed that all endometrial and ovarian cancer cell lines were sensitive
      to the growth inhibitory effect of apicidin, although normal endometrial
      epithelial cells were viable after the treatment with the same doses of apicidin
      that induced the growth inhibition of endometrial and ovarian cancer cells. Cell
      cycle analysis indicated that their exposure to apicidin decreased the proportion
      of cells in S-phase and increased the proportion in G0/G1 and/or G2/M phases of
      the cell cycle. Induction of apoptosis was confirmed by Annexin V staining of
      externalized phosphatidylserine and loss of the transmembrane potential of
      mitochondria. This induction occurred in concert with the altered expression of
      p21WAF1, p27KIP1, p16, cyclin A, and E-cadherin. Furthermore, apicidin treatment
      of these cell lines increased acetylation of H3 and H4 histone tails. These
      results suggest that apicidin exhibits the antiproliferative effects through
      selective induction of genes related to cell growth, malignant phenotype, and
      apoptosis. The findings raise the possibility that apicidin may prove
      particularly effective in the treatment of endometrial and ovarian cancers.

PMID- 17203206
TI  - Muscle creatine kinase/SV40 hybrid promoter for muscle-targeted long-term
      transgene expression.
AB  - Gene therapy for congenital protein deficiencies requires lifelong expression of
      a deficient protein. Current gene therapy approaches preferentially employ the
      strong cytomegalovirus (CMV) promoter/enhancer or its derivative CAG promoter;
      however, these promoters provide only temporary transgene expression. To create a
      promoter that enables long-lasting expression in muscle, hybrid promoters were
      constructed by coupling the muscle creatine kinase (MCK) enhancer to various
      strong promoters for enhancement of tissue specificity and improved
      transcriptional activity. A hybrid promoter containing the MCK enhancer and the
      simian virus 40 promoter (MCK/SV40 promoter) yielded long-term (>6 months)
      expression of a human secretory alkaline phosphatase (huSEAP) reporter gene
      following electrotransfer of the plasmid into mice, whereas expression using a
      conventional CMV or CAG promoter faded away within a few weeks. To explore the
      mechanism behind the sustained expression obtained with the MCK/SV40 promoter,
      mice were immunized with a LacZ expression plasmid driven by MCK/SV40 or a
      conventional promoter. Minimal cellular and humoral responses to LacZ were
      observed in MCK/SV40 promoter-treated animals, and mouse SEAP gene expression in
      vivo was successfully maintained by both the MCK/SV40 and conventional promoters.
      These results suggest that the lower immunogenicity of the MCK/SV40 promoter
      contributed to long-lasting gene expression in mice. Therefore, the MCK/SV40
      promoter may provide the basis for development of an effective transgene
      expression cassette for treatment of congenital protein deficiencies in which
      therapeutic proteins are recognized as foreign by the host immune system.

PMID- 17203207
TI  - Sequential assessment of the intrahepatic expression of epidermal growth factor
      and transforming growth factor-beta1 in hepatofibrogenesis of a rat cirrhosis
      model.
AB  - Responses of the liver to chronic injury include inflammation, regeneration and
      fibrosis, which finally lead to cirrhosis. The cause of liver cirrhosis appears
      to be impaired proliferative capability of hepatocytes caused by continuous
      hepatic damage, and subsequent accumulation of extracellular matrix produced by
      hepatic stellate cells (HSCs). Epidermal growth factor (EGF) and transforming
      growth factor-beta1 (TGF-beta1) play a crucial role in hepatocyte proliferation
      and hepatofibrogenesis, respectively. However, sequential analyses of the
      intrahepatic expression of EGF and TGF-beta1 in the course of cirrhosis
      development have not been examined fully. In the present study, liver cirrhosis
      was produced in rats by intraperitoneal administration of dimethylnitrosamine
      (DMN), and intrahepatic mRNA expression levels of proliferating cell nuclear
      antigen (PCNA), EGF and TGF-beta1 were quantitatively estimated by a real-time
      reverse transcription-polymerase chain reaction method. Histological and
      semiquantitative densitometric examination of liver sections revealed that the
      accumulation of extracellular matrix components was increased according to the
      period of DMN treatment. Histological examination of liver sections of rats
      treated with DMN for 4 and 6 weeks revealed pre-cirrhosis and cirrhosis,
      respectively. Intrahepatic mRNA expression levels of PCNA and EGF correlated
      well. Expression levels of both molecules were increased significantly during the
      course of cirrhosis development, but decreased significantly at the time of
      complete cirrhosis manifestation. In contrast, intrahepatic TGF-beta1 expression
      was increased significantly according to the period of DMN treatment, and reached
      a peak at the time of cirrhosis manifestation. These results suggest that
      proliferative capability of hepatocytes was impaired by continuous liver damage
      due, in part, to the decrease of a hepatocyte mitogen EGF, and that increased
      intrahepatic TGF-beta1 activated HSCs to retrieve space lost by hepatocyte
      destruction, resulting in complete cirrhosis manifestation.

PMID- 17203208
TI  - CD9 promotes adeno-associated virus type 2 infection of mammary carcinoma cells
      with low cell surface expression of heparan sulphate proteoglycans.
AB  - Recombinant adeno-associated virus (AAV) is a promising non-pathogenic vector in
      the emerging field of gene therapy. For AAV serotype 2 (AAV-2) infection,
      experimental evidence points to an involvement of heparan sulphate proteoglycans
      (HSPG), but also to the existence of additional receptors. We investigated a
      potential role of the tetraspanin CD9 in AAV-2 infection of breast cancer cells
      mainly because it binds to the heparin-binding EGF-like growth factor, suggesting
      that it may also interact with a heparin-binding virus. Among breast cancer cell
      lines, expression of HSPG or potential AAV-2 (co)-receptors was not found to
      correlate with transduction efficiency. In complete accordance with the role of
      CD9, blocking with anti-CD9 antibodies resulted in drastically decreased AAV-2
      transduction efficiencies in cell lines with low expression of HSPG. Furthermore,
      specific inhibition of CD9 expression with siRNA resulted in fewer transgene
      positive cells, whereas overexpression of CD9 in the breast cancer cell line T47D
      as well as in BT8Ca and BT12Ca rat glioma cells (with low background expression
      of HSPG and CD9) increased the number of AAV-transduced cells. The minimal
      epitope recognized by antibody 72F6, which most efficiently blocked AAV-mediated
      transgene expression, was deduced from the specific binding to peptides
      immobilized on colour-encoded microspheres consisting of the amino acid sequence
      PKKDV located in the large extracellular loop of CD9. Our results clearly point
      to an involvement of CD9 in the attachment, uptake or processing of AAV-2 by
      target cells expressing low amounts of HSPG, which may help to define cell
      populations accessible in AAV-based therapeutic applications.

PMID- 17203209
TI  - Interleukin-8 production via protease-activated receptor 2 in human esophageal
      epithelial cells.
AB  - Interaction between proteases and protease-activated receptor (PAR) 2 has been
      proposed to mediate inflammatory and immune response in the gastrointestinal
      tract. Recently, increase in interleukin (IL)-8 in the esophageal mucosa has been
      associated with the pathogenesis of esophagitis induced by reflux of gastric
      acids, bile acids or trypsin. The aims of the present study were to determine
      PAR2 expression in normal human esophageal epithelial cells (HEEC) and to
      evaluate the mediation of IL-8 production by trypsin-PAR2 interaction in HEEC.
      Reverse transcription polymerase chain reaction (RT-PCR) and Western blot
      analysis revealed that PAR2 mRNA and protein were constitutively expressed in
      HEEC without upregulation by the stimulation with tumor necrosis factor alpha or
      trypsin. IL-8 was produced in a dose-dependent fashion when cells were stimulated
      with a PAR2 agonist such as trypsin or SLIGKV-amide. Blocking antibody to PAR2,
      camostat mesilate (a trypsin inhibitor), p-38 mitogen-activated protein kinase
      (MAPK) inhibitors or ERK1/2 inhibitors reduced IL-8 production from trypsin
      stimulated HEEC. Mutation of the NFkappaB-, AP-1- and NF-IL-6-binding site on the
      IL-8 gene promoter abrogated the induction of luciferase activities stimulated
      with trypsin by 100, 80 and 50%, respectively. These results indicate that PAR2
      activation in HEEC by trypsin induces NFkappaB- and AP-1-dependent IL-8
      production in association with activation of p38 MAPK and ERK1/2, suggesting that
      esophageal inflammation may be induced by PAR2 activation via reflux of trypsin.

PMID- 17203210
TI  - Newer vascular targets: endosialin (review).
AB  - The identification of cell surface markers expressed selectively by tumor
      vasculature is challenging. To get as close to the human disease as possible,
      investigators have isolated endothelial cells from fresh human tumor specimens
      and subjected them to RNA-based gene expression analysis. The data indicate that
      there are few proteins that distinguish tumor vasculature from normal vasculature
      and re-enforce the notion that the endothelium is a tissue specialized cell-type.
      Endosialin was identified as a cell surface tumor endothelial marker. The
      selective expression of endosialin by tumor vasculature and stroma has been
      confirmed. Although the function of endosialin remains to be elucidated, the
      expression pattern for this protein may be favorable for cancer therapy.

PMID- 17203211
TI  - Arsenic trioxide induces apoptosis via the mitochondrial pathway by upregulating
      the expression of Bax and Bim in human B cells.
AB  - Arsenic trioxide (As2O3) has been approved for the treatment of acute
      promyelocytic leukemia (APML) and it is a promising candidate for the treatment
      of patients with lymphoproliferative disorders, such as relapsed or refractory
      multiple myeloma and myelodysplastic syndromes. The effects of As2O3 on B cells,
      specifically which do not express Bcl-2, have not been studied. In this study, we
      have demonstrated that As2O3, at clinically achievable therapeutic
      concentrations, induces apoptosis in Bcl-2 negative human B cell line Ramos.
      As2O3-induced apoptosis is associated with reduced mitochondrial transmembrane
      potential (delta psi), enhanced generation of intracellular reactive oxygen
      species (ROS), release of cytochrome c and apoptosis-inducing factor (AIF) from
      mitochondria into cytoplasm, activation of caspases, and upregulation of Bax and
      Bim expression. Exogenous glutathione (GSH) reverses the As2O3-induced apoptosis
      in a dose-dependent manner. Altogether, these data indicate that As2O3 induces
      apoptosis in B cells, regardless of Bcl-2 expression, via the mitochondrial
      pathway by enhancing oxidative stress.

PMID- 17203212
TI  - In vitro accumulation and permeation of hypericin and lipophilic analogues in 2-D
      and 3-D cellular systems.
AB  - Previous studies have shown that hypericin is an excellent diagnostic tool for
      the fluorescence detection of carcinoma in situ in the human bladder. The present
      work was performed to get a better insight into the mechanism of cellular uptake
      of hypericin (HYP) using RT-112 human papillary TCC cells of the bladder. Using
      lipophilic hypericin acid amide derivatives like hypericin acid hexylamide (AM6),
      hypericin acid octylamide (AM8) and hypericin acid dodecylamide (AM12), the
      effect of increased lipophilicity on the binding to serum proteins was
      investigated, as well as the cellular accumulation and permeation, both in 2-D
      and 3-D cell conditions. Density-gradient ultracentrifugation of the compounds
      pre-incubated with fetal bovine serum (FBS) showed that HYP and to a lesser
      extent AM6 predominantly bind to LDL, whereas AM8 and especially AM12 preferably
      associate with HDL. The cellular accumulation of the compounds did not
      significantly differ when LDL or AcLDL was supplemented to medium, and with all
      compounds the highest uptake could be observed in case of medium without
      supplements. Using medium without supplements it was further observed that the
      compounds with the highest lipophilicity accumulated substantially less in RT-112
      cells. We further found a significant difference in the intracellular
      concentration of AM8 and AM12 when LDL or FBS was supplemented to MEM, but not in
      case of HYP and AM6. Of particular interest, AM8 and especially AM12 showed
      enhanced intraspheroidal permeation in the presence of FBS. It is believed that
      the relative stronger binding to HDL reduces the intracellular accumulation, as
      seen in the 2-D conditions, and therefore increases the probability of
      paracellular transport in a 3-D multicellular system by passive diffusion. In
      conclusion the data suggest that the amount of free hypericin or its lipophilic
      congener determines the extent of intracellular accumulation. This concentration
      is both determined and limited by binding to different lipoproteins present in
      the medium, and by the formation of stable homoaggregates. The findings further
      highlight AM8 and AM12 as compounds better tailored for paracellular transport
      than HYP itself and therefore as potentially very interesting diagnostic tools
      for TCC lesions in the bladder.

PMID- 17203213
TI  - Increased invasive potential and up-regulation of MMP-2 in MDA-MB-231 breast
      cancer cells expressing the beta3 integrin subunit.
AB  - Integrins are a family of transmembrane adhesion receptors that might transduce
      signals from the extracellular matrix into the inside of cells after ligand
      binding. In order to investigate whether beta3 integrins expressed in tumor cells
      might mediate such outside-in signaling, human MDA-MB-231 breast cancer cells
      that were stably transfected with either beta3 integrin or mock-transfected were
      investigated in a matrigel degradation assay and a grafting experiment was
      performed on the developing chicken chorioallantoic membrane (CAM). After
      cultivation on matrigel for time periods between one and five days, more matrigel
      was digested in the wells in which beta3 integrin expressing cells were incubated
      than in wells of mock-transfected cells. Furthermore, extracts of beta3 integrin
      expressing cells contained higher levels of MMP-2 protein as determined by
      immunoblotting and more MMP-2 associated gelatinase activity as detected by
      zymography than extracts of mock-transfected cells. Matrigel degradation and
      gelatinase activity as well as MMP-2 expression were elevated when beta3 integrin
      expressing cells were incubated in the presence of the RGD peptide (mimicking an
      integrin ligand). After grafting on 10 day-old embryonic chicken CAM for three to
      five days, beta3 integrin expressing cells assembled in spheroids showed higher
      rates of spreading on the CAM surface and CAM invasion as well as a significant
      MMP-2 up-regulation compared to mock-transfected cells. The results from the in
      vivo and in vitro experiments allow the conclusion that the presence of beta3
      integrin in MDA-MB-231 breast cancer cells induced an increased MMP-2 expression
      and activity that might contribute to the enhanced invasive potential observed.

PMID- 17203214
TI  - Repression of cyclin D1 as a target for germ cell tumors.
AB  - Metastatic germ cell tumors (GCT) are curable, however GCTs refractory to
      cisplatin-based chemotherapy have a poor prognosis. This study explores D-type
      cyclins as molecular targets in GCTs because all-trans-retinoic acid (RA)
      mediated differentiation of the human embryonal carcinoma (EC) cell line NT2/D1
      is associated with G1 cell cycle arrest and proteasomal degradation of cyclin D1.
      RA effects on D-type cyclins are compared in human EC cells that are RA sensitive
      or dually RA and cisplatin resistant (NT2/D1-R1) and in clinical GCTs that have
      both EC and mature teratoma components. Notably, GCT differentiation was
      associated with reduced cyclin D1 but increased cyclin D3 expression. RA was
      shown here to repress cyclin D1 through a transcriptional mechanism in addition
      to causing its degradation. The siRNA-mediated repression of individual cyclin D
      species resulted in growth inhibition in both RA sensitive and resistant EC
      cells. Only repression of cyclin D1 occurred in vitro and when clinical GCTs
      mature, implicating cyclin D1 as a molecular therapeutic target. To confirm this,
      the EGFR-tyrosine kinase inhibitor, Erlotinib, was used to repress cyclin D1.
      This inhibited proliferation in RA and cisplatin sensitive and resistant EC
      cells. Taken together, these findings implicate cyclin D1 targeting agents for
      the treatment of GCTs.

PMID- 17203215
TI  - von Hippel Lindau tumor suppressor regulates hepatic glucose metabolism by
      controlling expression of glucose transporter 2 and glucose 6-phosphatase.
AB  - von Hippel Lindau (VHL) disease is a hereditary cancer syndrome caused by
      biallelic inactivation of the VHL tumor suppressor gene. The most widely known
      function of VHL is to limit normoxic protein expression of hypoxia-inducible
      factor-alpha (HIF-alpha). Loss of the functional VHL gene causes constitutive
      stabilization of HIF-alpha that primarily up-regulates hypoxia-inducible genes
      even at normal oxygen concentration, which in turn contribute to VHL tumor
      progression. We report on the novel function of VHL in hepatic glucose storage
      and disposal. VHL deletion in adult mouse liver quickly leads to increased
      accumulation of glycogen granules as well as lipid droplets. This abnormal
      glycogen storage in VHL-inactivated liver arises at least in part from
      significantly reduced expression of two key liver-specific glucose metabolism
      genes, glucose transporter-2 (GLUT2) and glucose-6-phosphatase (G-6-Pase). The
      expression pattern of these genes in VHL knock-out liver was in contrast to that
      of well-known HIF target genes, such as PGK, Glut-1, VEGF, and EPO, all of which
      are highly elevated upon VHL inactivation. Our findings suggest that two distinct
      signaling pathways exist at the downstream of VHL controlling different sets of
      gene expression. Following VHL inactivation, one pathway causes oxygen
      independent overexpression of classic hypoxia-inducible genes and the other one
      described here suppresses expression of the genes important for liver glucose
      metabolism.

PMID- 17203217
TI  - Requirement of Pygopus 2 in breast cancer.
AB  - The development of novel therapeutic strategies for breast cancer requires the
      identification of molecular targets involved in malignancy. Human Pygopus (Pygo)
      1 and -2 are recently discovered components of the Wnt signaling pathway required
      for beta-Catenin/Tcf dependent transcription in embryos and colorectal cancer
      cells, but the role of these proteins in malignant cell growth and survival has
      not yet been determined. We report the expression and requirement for
      proliferation of hPygo2 in breast cancer cells. hPygo2 protein was overexpressed
      in malignant breast tumors and in the nuclei of five breast cancer cell lines,
      but was not expressed in the nuclei of non-malignant breast cells.
      Phosphorothioated antisense oligonucleotides were used to specifically knockdown
      expression hPygo2 in Mcf-7 and MDA-MB-468 cell lines. hPygo2 was required for the
      growth, in tissue culture and anchorage-independent assays, of both cell lines
      and for the expression of the Wnt target gene Cyclin D1. We conclude that hPygo2
      is highly expressed in, and required for the growth of breast carcinoma cells.

PMID- 17203216
TI  - Decitabine and vitamin D3 differentially affect hematopoietic transcription
      factors to induce monocytic differentiation.
AB  - Standard chemotherapy is not curative for many patients with acute myeloid
      leukemia (AML). New treatment strategies combining demethylating agents, such as
      decitabine, and drugs that induce myelomonocytic differentiation (i.e. Vitamin
      D3) may re-establish functional hematopoiesis in these patients. We studied the
      effects of decitabine alone or in combination with Vitamin D3 (VD3) on U937 cells
      and AML blasts. Preincubation with decitabine (0.1-1 microM) and subsequent
      exposure to VD3 (3 nM) synergistically induced monocytic differentiation. To
      elucidate the mechanisms of decitabine- and VD3-induced monocytic
      differentiation, we investigated the effects of the two drugs on transcription
      factors implicated in monocytic differentiation. Northern and Western blotting
      showed that decitabine induced transcription of c-jun but not PU.1, while VD3
      increased PU.1, IRF8, and C/EBPbeta but not c-jun. Using electromobility shift
      assays, we demonstrated increased DNA binding of nuclear proteins from decitabine
      and VD3-induced U937 cells to the CD11b promoter. In addition, we investigated
      whether the myeloid transcription factor Sp1 played a role in decitabine- and VD3
      induced CD14 expression. Indeed, we found that mithramycin A, a specific
      inhibitor of Sp1, inhibited both VD3- and decitabine-induced upregulation of
      CD14, which is in line with previous data showing that Sp1 is critical for CD14
      promoter activity. Induction of CD11b and/or CD14 by decitabine and/or VD3 was
      confirmed in primary AML patient samples at the time of diagnosis. In conclusion,
      decitabine synergizes with Vitamin D3 to induce CD11b and CD14 expression, likely
      by enhancing PU.1/c-jun and Sp1 transcriptional activity.

PMID- 17203218
TI  - S-1 inhibits tumorigenicity and angiogenesis of human oral squamous cell
      carcinoma cells by suppressing expression of phosphorylated Akt, vascular
      endothelial growth factor and fibroblast growth factor-2.
AB  - It has been reported that S-1 can exert antitumor effects on various human
      cancers including oral squamous cell carcinoma (OSCC). However, little is known
      about the detailed mechanisms of the antitumor activity of S-1. In the present
      study, we determined whether S-1 could suppress the angiogenesis and growth of
      human OSCC cells in vitro and in vivo. The S-1 component (5-FU plus CDHP)
      significantly suppressed the growth and migration of OSCC cells and BAEC, which
      inhibited tubule formation in HUVECs in vitro. Also, S-1 inhibited the nuclear
      factor-kappaB (NF-kappaB) activity in human OSCC cells in vitro. Moreover, S-1
      inhibited the expression of survival signal, phosphorylated Akt (p-Akt), and of
      two major proangiogenic molecules, vascular endothelial growth factor (VEGF) and
      fibroblast growth factor-2 (FGF-2), in cells implanted into the subcutaneous
      tissue of nude mice. The decreased expression of p-Akt, VEGF and FGF-2 correlated
      with decreased tumorigenicity and decreased vascularization of lesions in vivo.
      These findings suggest that S-1 can suppress the angiogenesis and growth of OSCC
      cells by inhibiting the expression of p-Akt, VEGF and FGF-2 involved in the
      blockade of Akt/NF-kappaB pathway.

PMID- 17203219
TI  - Marked suppression of tumor growth by FTY720 in a rat liver tumor model: the
      significance of down-regulation of cell survival Akt pathway.
AB  - We aim to investigate the anticancer effect of a novel immunomodulator FTY720 on
      a rat orthotopic liver tumor model. A buffalo rat orthotopic liver tumor model
      was established by injection of a buffalo hepatoma cell line MH7777 into the
      right portal vein. FTY720 was administered by intraperitoneal injection starting
      at 10 days after tumor cell injection at a dosage of 5 mg/kg/day. FTY720 markedly
      suppressed tumor growth and inhibited tumor progression by selective induction of
      apoptosis of tumor cells via down-regulation of phospho-Akt(ser473) and up
      regulation of cleaved caspase-3, together with decrease of focal adhesion kinase.
      Moreover, the proliferation index of tumor cells was significantly reduced to
      15.92+/-5.03% by FTY720 compared with that of 42.92+/-4.47% in the control group
      (p<0.001). In addition, we confirmed that FTY720 caused no effect on infiltrated
      lymphocyte in tumor tissue. We conclude that FTY720 is an effective anticancer
      agent for liver tumor in a rat model without affecting the immune system of the
      host.

PMID- 17203220
TI  - Gene-specific inhibition of breast carcinoma in BALB-neuT mice by active
      immunization with rat Neu or human ErbB receptors.
AB  - Employing the transgenic BALB-neuT mouse tumor model, we explored the in vivo
      biologic relevance of immunocompetent epitopes shared among the four ErbB
      receptors. The outcome of neu-mediated tumorigenesis was compared following
      vaccination with isogeneic normal rat ErbB2/Neu (LTR-Neu) or xenogeneic human
      ErbB receptors (LTR-EGFR, LTR-ErbB2, LTR-ErbB3 and LTR-ErbB4), each recombinantly
      expressed in an NIH3T3 murine cell background. Vaccination using rat LTR-Neu at
      the stage of atypical hyperplasia potently inhibited neu-mediated mammary
      tumorigenesis. Moreover, all human ErbB receptors specifically interfered with
      tumor development in BALB-neuT mice. Relative increase in tumor-free survival and
      reduction in tumor incidence corresponded to structural similarity shared with
      the etiologic neu oncogene, as rat orthologue LTR-Neu proved most effective
      followed by the human homologue LTR-ErbB2 and the other three human ErbB
      receptors. Vaccination resulted in high titer specific serum antibodies, whose
      tumor-inhibitory effect correlated with cross-reactivity to purified rat Neu
      extracellular domain in vitro. Furthermore, a T cell response specific for
      peptide epitopes of rat Neu was elicited in spleen cells of mice immunized with
      LTR-Neu and was remotely detectable for discrete peptides upon vaccination with
      LTR-ErbB2 and LTR-EGFR. The most pronounced tumor inhibition by LTR-Neu
      vaccination was associated with leukocyte infiltrate and tumor necrosis in vivo,
      while immune sera specifically induced cytotoxicity and apoptosis of BALB-neuT
      tumor cells in vitro. Our findings indicated that targeted inhibition of neu
      oncogene-mediated mammary carcinogenesis is conditional upon the immunization
      schedule and discrete immunogenic epitopes shared to a variable extent by
      different ErbB receptors.

PMID- 17203221
TI  - Multidrug resistance-associated protein 7 expression is involved in cross
      resistance to docetaxel in salivary gland adenocarcinoma cell lines.
AB  - The aim of the present study was to clarify whether ATP binding cassette
      transporters are refractory factors in head and neck cancers. For in vitro and in
      vivo chemotherapeutic studies, we used the following head and neck cancer cell
      lines: a mouse oral squamous cell carcinoma (SCC) cell line, Sq-1979; a human SCC
      cell line, SCCHA; a mouse salivary gland adenocarcinoma (SGA) cell line, NR-PG;
      and a human SGA cell line, HSY. We used a vinca alkaloid anticancer drug,
      vincristine (VCR), as a chemotherapeutic anticancer drug. To determine the cause
      of multidrug resistance, Western blot analysis, reverse transcription-polymerase
      chain reaction (RT-PCR), immunohistochemistry of xenografted tumors in nude mice,
      drug efflux analysis, and drug efflux inhibitory assays were performed. VCR
      treated cell lines, Sq-1979/VCR, SCCHA/VCR, NR-PG/VCR, and HSY/VCR, intensively
      expressed multidrug resistance (MDR) gene 1 mRNA and multidrug resistance
      associated protein (MRP) 1 mRNA. MRP7 mRNA and protein were expressed in NR
      PG/VCR and HSY/VCR cells, but not in Sq-1979/VCR and SCCHA/VCR cells. In each
      cell clone of NR-PG/VCR and HSY/VCR, MRP7 mRNA was induced by VCR treatment,
      suggesting an acquired resistance to VCR in the context of MRP7 expression. In
      the in vivo chemotherapeutic nude mice model, VCR-treated xenografted SCCHA and
      HSY cells expressed MDR1 and MRP1. Moreover, MRP7 expression was
      immunohistochemically found in xenografted HSY cells of VCR-injected tumor
      bearing mice, but not in SCCHA cells. Furthermore, doxorubicin accumulation was
      increased and drug cross-resistance to docetaxel decreased in HSY/VCR in the
      presence of a competitive MRP7 inhibitor, 17-beta-estradiol-(17-beta-D
      glucuronide). These results indicate that MDR1 expression, MRP1 expression, and
      MRP7 expression are refractory factors in head and neck cancer chemotherapy and
      suggest that induction of MRP7 expression is involved in drug resistance to
      natural products, especially to docetaxel in SGA.

PMID- 17203222
TI  - STI571 sensitizes nasopharyngeal carcinoma cells to cisplatin: sustained
      activation of ERK with improved growth inhibition.
AB  - Previously, we demonstrated that c-kit and stem cell factors (SCF) commonly co
      expressed in primary and metastatic nasopharyngeal carcinomas (NPC), and in HONE
      1 NPC cells with tyrosine autophosphorylation of c-kit. These findings suggest
      that the SCF/c-kit signaling may contribute to pathogenesis of NPC. Therefore,
      the efficacy of STI571 treatment alone and when combined with cisplatin on HONE-1
      cells were evaluated. STI571 induced growth inhibition at the IC50 concentration
      (14.9 microM). When the concentration was at or higher than 30 microM, the
      induction of cell apoptosis was observed. The effects of STI571 were shown to be
      mediated by the sustained activation of ERK but did not involve the inhibition of
      c-kit signal activity. When the STI571 (5 microM) and cisplatin (5 microg/ml)
      treatments were combined, there were further inductions of ERK activation
      resulting in obviously enhanced growth inhibition and induction of cell
      apoptosis. In a xenograft model, STI571 (50 mg/kg/day) showed only a limited
      ability to inhibit HONE-1 cell growth, but when combined with cisplatin (3
      mg/kg/twice a week) treatment, there was a significant improvement in growth
      inhibition compared with STI571 or cisplatin treatment alone. Our results provide
      experimental support for the advanced NPC therapeutic trials using the combined
      STI571 and cisplatin treatment.

PMID- 17203223
TI  - cDNA analysis of gene expression associated with DNA-dependent protein kinase
      activity.
AB  - DNA-dependent protein kinase (DNA-PK) is thought to play a pivotal role in DNA
      double-strand break repair. We recently demonstrated the association of DNA-PK
      activity in peripheral blood lymphocytes (PBL) with the incidence of chromosomal
      aberrations and the risk of cancer. In this study, we applied cDNA array
      technology to find the expression of genes which are associated with DNA-PK
      activity in PBLs with various levels of DNA-PK activity. Most genes correlated
      with DNA-PK activity involved cell cycle regulation. Moreover, the transcription
      factor E2F1, which plays an important role in cell cycle progression, exhibited
      strong correlation with the DNA-PK activity and Rbp130, which is considered a
      negative regulator of E2F, showed inverse correlation with DNA-PK activity. In
      silico promoter analyses showed the presence of at least one E2F binding site in
      the promoter regions of Ku70, Ku86, DNA-PKcs and genes associated with DNA-PK
      activity. In order to examine the relationship among the E2F1 expression, the
      expression of genes related with DNA-PK activity, and DNA-PK activity, we
      activated PMLs by PHA to progress the cell cycle. After PHA activation of PML,
      the expression of E2F1 and DNA-PK activity increased. The expression of most
      genes in PHA-stimulated PBLs had a similar relationship with DNA-PK activity to
      that without PHA stimulation. These results indicate that the E2F transcription
      factor may regulate the concerted expression of genes related with DNA-PK
      activity.

PMID- 17203224
TI  - A novel gene, RSRC2, inhibits cell proliferation and affects survival in
      esophageal cancer patients.
AB  - In Japan and China, esophageal cancer is common and more than 90% of esophageal
      cancers are squamous cell carcinoma. Esophageal squamous cell carcinoma (ESCC)
      shows a poor prognosis, but the mechanism of ESCC and target genes for treatment
      remains unclear. We searched for genes related to ESCC, and identified a novel
      gene, FLJ11021, which was designated arginine/serine-rich coiled-coil 2 (RSRC2).
      We sought to determine the role of RSRC2 in the proliferation of esophageal cell
      lines and to examine the relationship between RSRC2 and clinicopathologic factors
      and ESCC prognosis. Expression of RSRC2 was quantified by real-time reverse
      transcription polymerase chain reaction (RT-PCR) in 70 primary ESCCs and paired
      noncancerous esophageal mucosa. To determine the role of RSRC2 in ESCC cell
      proliferation, we used vector-based transfection and small interfering RNA
      methods. Our results show that RSRC2mRNA levels in all ESCC cell lines (TE1-15,
      excluding TE7) were lower than those in a human esophageal squamous epithelial
      cell line (Het-1A). Cell proliferation of an ESCC cell line was inhibited by
      overexpression of RSRC2, while reduced expression was accompanied by tumor
      progression. RSRC2 expression levels were significantly correlated with depth of
      invasion, lymph node metastasis, lymphatic invasion and vascular invasion.
      Moreover, ESCC patients with low RSRC2mRNA expression had significantly shorter
      post-operative survival time than those with high expression. In vitro study
      revealed that RSRC2 might play a role in cell proliferation. Our study
      demonstrated that RSRC2 expression may be a novel tumor suppressor of esophageal
      cancer cell growth and a prognostic factor in ESCC.

PMID- 17203225
TI  - Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours.
AB  - Beclin 1 is is an autophagy gene, the role of which as a tumour suppressor has
      recently been recognized in a few studies. We examined the expression of Beclin 1
      protein in 212 primary human brain tumours, including 97 high-grade glial
      tumours, 29 low-grade glial tumours, 4 grade III meningiomas, 19 grade II
      meningiomas, 52 grade I meningiomas, and 11 medulloblastomas. In 94 cases,
      including 56 glial tumours, 35 meningiomas, and 3 medulloblastomas we also
      assessed Beclin 1 mRNA expression by real-time RT-PCR. In most high-grade
      astrocytic, ependymal neoplasms and atypical meningiomas we found a decrease of
      cytoplasmic protein expression that was, instead, high in the majority of low
      grade tumours and in medulloblastomas. The expression level of Beclin 1 mRNA was
      significantly lower in glioblastomas than in grade II (p=0.04) and grade I
      (p=0.01) astrocytomas; in grade III than in grade I astrocytomas (p=0.01); in
      grade II than in grade I meningiomas (p=0.03); and in all glial tumours when
      compared to all meningiomas (p<0.0001). Cytoplasmic expression is thought to be
      linked to the functional protein. Our observations are in line with studies that
      demonstrated decreased expression of Beclin 1 in human breast, ovarian, prostate
      and ovarian cancer and furtherly support its involvement also in brain tumours,
      which had previously been demonstrated in a few experimental studies, both in
      spontaneous and in therapy-induced autophagy. Furthermore, our study suggests
      possible differences of Beclin 1 involvement and its role among the different
      histotypes of brain neoplasms. Further studies are needed to highlight Beclin 1
      function in tumour suppression and/or in tumour survival through autophagy and
      other related programmed cell death processes in brain tumours.

PMID- 17203226
TI  - Expression of p-STAT3 in human gastric carcinoma: significant correlation in
      tumour invasion and prognosis.
AB  - Signal transducers and activators of transcription (STATs) belong to a family of
      transcription factors activated in response to cytokines and growth factors.
      Constitutive activation of STAT3 has been observed in a growing number of tumour
      derived cell lines, as well as in tumor specimens from human cancers. Our aim was
      to determine the relationship between the expression of phosphorylated STAT3 (p
      STAT3) and clinicopathological factors in human gastric adenocarcinoma. One
      hundred and eleven cases of surgically resected human gastric adenocarcinoma were
      studied by immunohistochemistry. Fifty-five (49.5%) cases showed positive
      staining for the p-STAT3 proteins. The expression of p-STAT3 was significantly
      correlated with several clinicopathological factors. Moreover, expression of p
      STAT3 was detected by Western blot analysis in 2 different kinds of cultured
      human gastric carcinoma cell lines and 4 cases of gastric carcinoma tissue
      obtained at surgery. Western blot analysis confirmed the presence of p-STAT3 in
      these specimens. In univariate survival analysis, p-STAT3 expression was
      associated with inferior survival (p<0.05). Constitutive activation of STAT3 may
      play an important role in the tumorigenesis of gastric adenocarcinoma, and the
      detailed mechanism of STAT3 signaling pathway in gastric adenocarcinoma deserves
      further investigation.

PMID- 17203228
TI  - Combretastatin A-4-phosphate effectively increases tumor retention of the
      therapeutic antibody, 131I-A5B7, even at doses that are sub-optimal for vascular
      shut-down.
AB  - Radioimmunotherapy using 131I-A5B7, an anti-CEA antibody, in combination with the
      vascular disrupting agent, combretastatin A4-phosphate (CA-4-P, 200 mg/kg), has
      produced tumor cures in SW1222 colorectal xenografts. CA-4-P causes acute tumor
      blood vessel shutdown, which can be monitored in clinical trials using dynamic
      contrast enhanced magnetic resonance imaging (DCE-MRI). The purpose of this study
      was to determine the magnitude of the anti-vascular effect of CA-4-P in the
      SW1222 tumor, at 200 mg/kg and at lower, more clinically relevant doses, using
      conventional assays; relate effects to changes in DCE-MRI parameters and
      determine the corresponding effects on tumor retention of 131I-A5B7. The tumor
      vascular effects of 30, 100 and 200 mg/kg CA-4-P were determined, at 4- and 24-h
      post-treatment, using DCE-MRI, uptake of Hoechst 33342 for tumor vascular volume
      and conventional histology for necrosis. The effect of CA-4-P on tumor and normal
      tissue 131I-A5B7 retention was also determined. A significant reduction in tumor
      DCE-MRI kinetic parameters, the initial area under the contrast agent
      concentration time curve (IAUGC) and the transfer constant (Ktrans), was
      demonstrated at 4 h after CA-4-P, for all dose levels. These effects persisted
      for at least 24 h for the 200 mg/kg group but not for lower doses. A similar
      pattern was seen for vascular volume and necrosis. Despite this dose response,
      all three dose levels increased tumor retention of radio labeled antibody to a
      similar degree. These results demonstrate that moderate tumor blood flow
      reduction following antibody administration is sufficient to improve tumor
      antibody retention. This is encouraging for the combination of CA-4-P and 131I
      A5B7 in clinical trials.

PMID- 17203227
TI  - Combined effect of temozolomide and hyperthermia on human melanoma cell growth
      and O6-methylguanine-DNA methyltransferase activity.
AB  - Hyperthermic isolated limb perfusion (HILP) with L-phenylalanine mustard (L-PAM)
      represents an effective treatment for locally advanced melanoma of the limbs.
      However, regional chemotherapy of melanoma still needs to be improved.
      Temozolomide (TMZ) is a methylating agent that spontaneously decomposes into the
      active metabolite of dacarbazine, the most effective agent for the systemic
      treatment of melanoma. Tumor cells with high levels of O6-methylguanine-DNA
      methyltransferase (MGMT) and/or with a defective DNA mismatch repair (MMR) are
      resistant to TMZ. Inhibition of MGMT activity increases TMZ sensitivity of MMR
      proficient, but not of MMR-deficient cells, while inhibition of base excision
      repair (BER) potentiates TMZ cytotoxicity in both cell types. Recent studies,
      performed in an animal model, have shown that TMZ is more effective than L-PAM
      when applied regionally and that hyperthermia can increase the antitumor activity
      of TMZ. In this study, three thermoresistant human melanoma cell lines, endowed
      with different MGMT activity and functional status of the MMR system, were
      treated with TMZ at 37 degrees C or 41.5 degrees C for 90 min, and then analyzed
      for cell growth and MGMT activity. Hyperthermia significantly enhanced TMZ
      cytotoxicity in MMR-proficient cells, either endowed or not with MGMT activity,
      and in MMR-deficient cells. Endogenous MGMT activity was not affected by
      hyperthermia that, however, enhanced the enzyme depletion induced by TMZ
      treatment. Moreover, MGMT recovery after drug removal was delayed in cells that
      had been treated at 41.5 degrees C. Taken together, these findings confirm the
      therapeutic potential of a combined treatment of hyperthermia and TMZ. They also
      suggest that inhibition of BER and/or increased DNA methylation may be involved
      in the thermal enhancement of TMZ cytotoxicity. Additional studies are necessary
      to better clarify the mechanisms underlying hyperthermia-induced potentiation of
      TMZ activity. However, the present investigation provides further support to the
      development of clinical trials of HILP with TMZ.

PMID- 17203229
TI  - Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen
      recognized by the humoral immune system.
AB  - Since the prognosis of human osteosarcoma in advanced stage remains poor, the
      development of new and effective therapies including immunotherapy is required.
      To identify tumor-associated antigens of osteosarcoma applicable to the
      immunotherapy of this malignancy, we employed the serological analysis of
      recombinant cDNA expression library (SEREX) technique that defines tumor antigens
      recognized by the humoral immune system. Screening a cDNA library derived from an
      osteosarcoma cell line MG63 with sera from osteosarcoma patients identified 43
      positive clones, representing 14 distinct antigens. Among them, CLUAP1 (clusterin
      associated protein 1) was highly expressed in osteosarcoma tissue samples and
      cell lines. Overexpression of CLUAP1 was observed in other malignancies including
      ovarian, colon, and lung cancers. Our results suggest that CLUAP1 may be useful
      as a prognostic/diagnostic marker and/or for a target of immunotherapy of
      osteosarcoma.

PMID- 17203230
TI  - Interferon-alpha inhibits in vitro osteoclast differentiation and renal cell
      carcinoma-induced angiogenesis.
AB  - Bone is a common site of osteolytic and richly vascularized metastases of renal
      cell carcinoma (RCC) and Interferon (IFN)-alpha based therapies have been
      considered for the treatment of patients affected by this disease. The effects of
      IFN-alpha on metastatic RCC patients have been related to its immunomodulatory,
      and cytotoxic activity on tumor cells, but there could be an effect also on tumor
      induced osteoclast differentiation and bone angiogenesis. When osteoclasts
      obtained from human peripheral blood mononuclear cells, cultured in the presence
      of receptor activator of nuclear factor-kappaB (RANKL) and macrophage-colony
      stimulating factor (M-CSF), were treated with IFN-alpha, the expression of bone
      tartrate resistant acid phosphatase (TRACP) type 5b was reduced, as well as
      calcium-phosphate resorption activity and expression of pro-osteoclatic
      transcription factor c-Fos. IFN-alpha modulation of angiogenesis was studied by
      analysis of proliferation, survival, and migration of a bone endothelial cell
      line (BBE), and by the analysis of pro-angiogenic factor expression in RCC cell
      lines. IFN-alpha inhibited bone endothelial cell proliferation and the expression
      of FGF-2, while the vascular endothelial growth (VEGF) did not show any
      significant variation. Moreover, IFN-alpha inhibited the migration induced by the
      RCC through the impairment of fibroblast growth factor-2 (FGF-2) secretion. These
      data demonstrate multiple activities of IFN-alpha on renal cancer-induced bone
      disease, in addition to its recognized role as a cytotoxic and immunomodulatory
      agent, because they indicate its ability to reduce bone resorption and to impair
      tumor-associated angiogenesis, and they also suggest the use of IFN-alpha to
      treat skeletal metastases of other carcinomas.

PMID- 17203231
TI  - Effects of 4-hydroxytamoxifen, raloxifene and ICI 182 780 on survival of uterine
      cancer cell lines in the presence and absence of exogenous estrogens.
AB  - The impact of 17beta-estradiol and antiestrogens on uterine cancer cells is
      poorly understood. The aim of this study was to determine the impact of 17beta
      estradiol, 4-hydroxytamoxifen, raloxifene and ICI 182 780 on the cell
      proliferation of six uterine cancer cell lines: HeLa, HEC-1-A, KLE, RL-95-2,
      Ishikawa and EN-1078D. The effects of these compounds on the cell proliferation
      of the six uterine cancer cell lines were studied in the presence and absence of
      estrogens (phenol red and serum deprivation of sex steroids). In a general
      manner, 17beta-estradiol and 4-hydroxytamoxifen showed similarities in their
      effects whereas raloxifene showed a different pattern of cell proliferation
      (agonistic and antagonistic) and ICI 182 780 had antagonistic activity. In the
      presence and absence of estrogens, we observed that each cell line had diverse
      expression of ERalpha, ERbeta, GPR30 and REA. GPR30 mRNA expression was
      significantly reduced in a serum/phenol-free medium. REA mRNA expression was not
      influenced by the media. Results demonstrated the importance of removing phenol
      red and the use of deprived serum when studying uterine cancer cells in
      relationship with 17beta-estradiol and antiestrogens. The affinity of each
      compound to the binding of ERalpha and ERbeta was very similar with the exception
      of raloxifene that had a preference for ERalpha binding. Akt
      phosphorylation/activity was reduced in cells cultured in a phenol red- and
      steroid-free culture medium indicating that the presence of steroids in the
      culture media can influence the activity of this survival pathway. Our results
      suggest that the expression of ERalpha, ERbeta and GPR30 are influenced by sex
      steroids and might play a role in the response of cells to 17beta-estradiol and
      antiestrogens but are not the only factors involved in this process.

PMID- 17203232
TI  - Intestinal MUC2 and gastric M1/MUC5AC in preneoplastic lesions induced by 1,2
      dimethylhydrazine in rat: a sequential analysis.
AB  - Our study was performed to sequentially analyze the expression of the intestinal
      mucin MUC2 and of the gastric mucin MUC5AC as indicators during progression of
      preneoplastic biomarkers in rat colon. F344 rats were sacrificed 2, 4, 8, 12, 24
      and 36 weeks after injection of 1,2-dimethylhydrazine (DMH, 200 mg/kg, i.p.). The
      expression of MUC2 and of MUC5AC was studied by immunohistochemistry in
      preneoplastic lesions classified in two categories: histologically altered foci
      (HAF) and beta-catenin accumulated crypts (BCAC). HAF appeared 4 weeks after DMH
      injection. Their crypt multiplicity stagnated with time (3-4 crypts/foci) but
      gastric MUC5AC mucin was always observed in some goblet cells of the lesions of
      this category. In contrast, MUC2-immunostaining was not modified compared to the
      adjacent crypts. Double-immunofluorescence revealed that goblet cells which
      produced MUC5AC continued to express MUC2. In BCAC, crypt multiplicity and mucin
      expression strongly evolved with time. These lesions were observed only 8 weeks
      after DMH-injection. At this stage, 20% of BCAC showed a decreased MUC2
      expression and 33% were MUC5AC immunopositive. At the 36-week point, 43% of BCAC
      had a reduced MUC2 staining and 90% were positive for MUC5AC. This
      immunopositivity was often observed in all the cells of these lesions. Seldom,
      some BCAC were depleted at the same time in MUC2 and in MUC5AC. Similar
      alterations in mucin expression were observed in human colonic pre-neoplastic
      lesions. These findings suggest that a decrease in MUC2 expression and staining
      of MUC5AC in non-goblet-like cells predicts histological progression of
      preneoplastic lesions.

PMID- 17203233
TI  - An imbalance between Smad and MAPK pathways is responsible for TGF-beta tumor
      promoting effects in high-grade gliomas.
AB  - The transforming growth factor-beta (TGF-beta) plays a pivotal role in the
      pathobiology of human gliomas: during carcinogenesis, it turns from a tumor
      suppressor to a tumor promoter. The traditional Smad pathway and the more
      recently discovered MAPK pathway are the most important pathways for TGF-beta
      related intracellular signal transduction mediating differential pathobiological
      effects. In this study, we investigated the effects of TGF-beta2 and the TGF
      beta2 antisense phosphorothioate oligodeoxynucleotide (PTO) AS-11 on the
      functionality of both the Smad and MAPK pathways in high-grade gliomas. We aimed
      to correlate the imbalance between the pathways with differences in the behaviour
      of high-grade glioma cells. Gene and protein expression studies were used to
      detect levels of members of the Smad and MAPK pathways under regulation of TGF
      beta2 and AS-11. Proliferation and migration assays were functional readouts for
      effects caused by these regulating tools. Gene arrays were used to detect yet
      unknown regulators of these functional effects. The Smad pathway was functional
      in the tested cell lines. Exogenous TGF-beta2 inhibited proliferation but
      enhanced migration. Smad 2 mRNA expression and activation were significantly
      reduced by incubation with AS-11. K-ras was reduced both in gene arrays and quPCR
      under treatment with AS-11, but there was no influence of K-ras down-regulation
      on the activity of ERK. Ubiquitination-related genes also were specifically down
      regulated with AS-11. Our results indicate the involvement of K-ras in TGF-beta
      signaling in high-grade gliomas. ERK, which is a member of the MAPK pathway, was
      not influenced and seems to be activated through RAS independent cascades in
      glioma. These results suggest that combined antagonization of the TGF-beta and
      MAPK pathways might be a promising approach for glioma therapy. An imbalance
      between these two pathways might be responsible for TGF-beta switching to a tumor
      promoter protein in high-grade gliomas.

PMID- 17203234
TI  - Role for HER2/neu and HER3 in fulvestrant-resistant breast cancer.
AB  - Tamoxifen resistance is common for estrogen receptor alpha (ERalpha) positive
      breast cancer. Second-line therapies include aromatase inhibitors or fulvestrant.
      We have shown previously that fulvestrant reversed 17beta-estradiol-induced tumor
      regression of tamoxifen-stimulated MCF-7 xenografts (MCF-7TAMLT) treated for >5
      years with tamoxifen in athymic mice and paradoxically stimulated growth. We
      investigated mechanisms responsible for growth by fulvestrant in the presence of
      physiologic estradiol and therapeutic strategies in vivo. The results
      demonstrated that only estradiol increased expression of the estrogen-responsive
      genes, c-myc, igf-1, cathepsin D, and pS2 mRNAs, in MCF-7E2 and MCF-7TAMLT
      tumors. Tamoxifen or fulvestrant decreased the estradiol-induced increase of
      these mRNAs in both tumor models. However, tyrosine-phosphorylated HER2/ neu,
      HER3, phospho-extracellular-regulated kinase-1/2 (ERK-1/2), and phospho-glycogen
      synthetase kinase 3alpha (GSK3alpha) and beta proteins were increased in MCF
      7TAMLT tumors treated with fulvestrant compared to estradiol, control, or
      tamoxifen. Phospho-HER2/neu interacted with HER3 protein in MCF-7TAMLT tumors. In
      order to determine whether the functional interaction of HER2/neu with HER3 is
      critical for growth of fulvestrant-stimulated MCF-7TAMLT tumors, pertuzumab (an
      antibody that blocks HER2/neu-HER3 interaction) was used in an in vivo xenograft
      growth assay. Only growth of fulvestrant-treated MCF-7TAMLT xenografts was
      decreased significantly by 37.2% in response to pertuzumab (P=0.004). Pertuzumab
      specifically decreased the interaction of HER2/neu protein with HER3 in
      fulvestrant-stimulated MCF-7TAMLT tumors. These results suggested growth of MCF
      7TAMLT tumors by tamoxifen or fulvestrant is potentially independent of ERalpha
      transcriptional activity as evidenced by lack of induction of four estrogen
      responsive genes. The results suggested that growth of MCF-7TAMLT tumors treated
      with fulvestrant in the presence of physiologic estradiol is in part mediated
      through enhanced signaling from the HER2/neu-HER3 pathway as pertuzumab partially
      inhibited growth and the interaction of HER2/neu with HER3 in vivo.

PMID- 17203235
TI  - Hepatocyte growth factor up-regulates the expression of the bone morphogenetic
      protein (BMP) receptors, BMPR-IB and BMPR-II, in human prostate cancer cells.
AB  - Hepatocyte growth factor (HGF) plays multiple roles in cancer, by acting as a
      motility, invasion and angiogenesis stimulating factor, which promotes metastasis
      and tumour growth. Bone morphogenetic proteins (BMPs) are members of the TGF-beta
      superfamily. The effects of BMPs are mediated by two subgroups of receptors, type
      I and type II. Recent studies have shown that some BMPs, via their signaling
      pathways, affect the growth of prostate cancer cells. BMPR-IB and BMPR-II have
      been reported to be expressed at low levels in prostate cancer. However, little
      is known about the crosstalk between HGF and BMP pathways. In this study,
      prostate cancer cells (PC-3 and DU-145) were exposed to HGF at different
      concentrations (1-75 ng/ml) for 18 h, or were treated with HGF at 40 ng/ml over
      various time periods (up to 24 h). The effect of HGF on BMP receptor expression
      was further investigated in a nude mouse PC-3 xenograft model. Mice were treated
      with either HGF, the HGF antagonist NK4, or a combination of both. The expression
      of BMPR-IB and BMPR-II mRNA was up-regulated by HGF, as shown by both
      conventional PCR and quantitative PCR. An elevation of BMPR-IB and BMPR-II at the
      protein level was confirmed by both Western blot analysis and immunocytochemical
      staining. In a murine prostate tumour model, infusion of recombinant HGF resulted
      in an increase in the levels of both BMPR-IB and BMPR-II transcript in prostate
      tumours. Concomitant delivery of NK4, an HGF antagonist, prevented this effect.
      In conclusion, HGF up-regulates the expression of the bone morphogenetic protein
      receptors, BMPR-IB and BMPR-II, in prostate cancer cells, both in vitro and in
      vivo. This may have important implications in the development of bone metastasis
      in prostate cancer.

PMID- 17203236
TI  - The quantification inventory for somatoform syndromes (QUISS): a novel instrument
      for the assessment of severity.
AB  - BACKGROUND: To date, specific scales for the assessment of severity of somatoform
      disorders are still rare. Characteristic cognitive and behavioural domains,
      representing severity are not incorporated in the existing scales. Results with
      the novel quantification inventory for somatoform syndromes (QUISS) are presented
      in this paper. METHODS: The QUISS has been developed as a qualified severity
      scale for patients fulfilling diagnostic criteria according to DSM-IV or/and ICD
      10. It was designed to be particularly suitable for application in clinical
      trials and for monitoring the efficacy of psychotherapy and pharmacotherapy. Not
      only number, severity and frequency of somatoform symptoms, but also common
      cognitive and behavioural domains of somatoform disorders have been included into
      this instrument. Both an 18-item patient- and observer-rated version are
      available taking about 20 min to complete. The questionnaire was applied to
      patients with somatoform disorder (N = 96), major depression (N = 24), and panic
      disorder (N = 16). RESULTS: The psychometric properties of the scale are
      satisfactory. The QUISS showed high objectivity (Cronbach's alpha = 0.90 for both
      versions; inter-scale correlations r = 0.64-0.88; p < 0.05), good test-retest- (r
      = 0.87; p < 0.05) and inter-rater-reliability (r = 0.89; p < 0.05). External
      validity (moderately high correlations of QUISS-T to SOMS 7T (r = 0.54),
      significant discrimination to major depression p < 0.05) was satisfactory. Factor
      structure revealed five relevant factors. CONCLUSIONS: The QUISS could be a
      useful instrument in somatoform disorders for the assessment of syndrome severity
      and treatment outcome in scientific and clinical settings.

PMID- 17203237
TI  - Mental health problems among single and partnered mothers. The role of financial
      hardship and social support.
AB  - BACKGROUND: Research has shown elevated levels of common mental disorders among
      single mothers compared with partnered mothers. The objectives of this analysis
      were to examine the prevalence of mental health problems among single and
      partnered mothers and the extent to which this relationship is mediated by socio
      demographic, financial and social support variables. METHODS: Using cross
      sectional data from a large, nationally representative longitudinal Australian
      household survey--the Household Income and Labour Dynamics in Australia (HILDA)
      Survey--the prevalence of moderate to severe mental disability (as measured by
      the SF-36) was assessed among 354 single mothers and 1,689 partnered mothers. A
      series of univariate and simultaneous logistic regression analyses assessed the
      association between parenting status, the other explanatory variables and mental
      disability. Mediational analyses were conducted using the 'explained fraction'
      approach. RESULTS: The prevalence of moderate to severe mental disability was
      significantly more pronounced among single mothers (28.7%) compared with
      partnered mothers (15.7%). Including all explanatory factors--socio-demographic,
      household income, financial hardship and social support--accounted for 94% of the
      association between single mother status and poor mental health. Financial
      hardship and social support were the strongest predictors, accounting for most of
      the predictive power of the other variables. CONCLUSIONS: Single mothers are more
      likely to experience poor mental health than partnered mothers, and the primary
      factors associated with this are the presence of financial hardship in
      particular, as well as perceived lack of social support. Future research should
      examine the extent to which changes in financial hardship among different family
      types relate to changes in mental health over time, as well as continue to
      examine variables that may moderate the relationship between social disadvantage
      and poor mental health.

PMID- 17203239
TI  - Astrobiology and Earth's geological record.

PMID- 17203240
TI  - Correlation in a Gaussian chain with the ends fixed.
AB  - We consider an ideal chain whose ends are fixed without fluctuation at different
      points, possibly by optical tweezers. We derive a two-point probability
      distribution of a corresponding random walk and explicitly calculate the
      scattering function. We find that the contour plot of the resulting function
      shows a kind of normal butterfly pattern, contaminated by wavy texture. These
      results are compared with some representative previous models.

PMID- 17203238
TI  - Molecular imaging of brain tumors: a bridge between clinical and molecular
      medicine?
AB  - As the research on cellular changes has shed invaluable light on the
      pathophysiology and biochemistry of brain tumors, clinical and experimental use
      of molecular imaging methods is expanding and allows quantitative assessment. The
      term molecular imaging is defined as the in vivo characterization and measurement
      of biologic processes at the cellular and molecular level. Molecular imaging sets
      forth to probe the molecular abnormalities that are the basis of disease rather
      than to visualize the end effects of these molecular alterations and, therefore,
      provides different additional biochemical or molecular information about primary
      brain tumors compared to histological methods "classical" neuroradiological
      diagnostic studies. Common clinical indications for molecular imaging contain
      primary brain tumor diagnosis and identification of the metabolically most active
      brain tumor reactions (differentiation of viable tumor tissue from necrosis),
      prediction of treatment response by measurement of tumor perfusion, or ischemia.
      The interesting key question remains not only whether the magnitude of
      biochemical alterations demonstrated by molecular imaging reveals prognostic
      value with respect to survival, but also whether it identifies early disease and
      differentiates benign from malignant lesions. Moreover, an early identification
      of treatment success or failure by molecular imaging could significantly
      influence patient management by providing more objective decision criteria for
      evaluation of specific therapeutic strategies. Specially, as molecular imaging
      represents a novel technology for visualizing metabolism and signal transduction
      to gene expression, reporter gene assays are used to trace the location and
      temporal level of expression of therapeutic and endogenous genes. Molecular
      imaging probes and drugs are being developed to image the function of targets
      without disturbing them and in mass amounts to modify the target's function as a
      drug. Molecular imaging helps to close the gap between in vitro and in vivo
      integrative biology of disease.

PMID- 17203241
TI  - Can electrons travel through actin microfilaments and generate oxidative stress
      in retinol treated Sertoli cell?
AB  - In early reports our research group has demonstrated that 7 microM retinol
      (vitamin A) treatment leads to many changes in Sertoli cell metabolism, such as
      up-regulation of antioxidant enzyme activities, increase in damage to
      biomolecules, abnormal cellular division, pre-neoplasic transformation, and
      cytoskeleton conformational changes. These effects were observed to be dependent
      on the production of reactive oxygen species (ROS), suggesting extra-nuclear (non
      genomic) effects of retinol metabolism. Besides 7 microM retinol treatment
      causing oxidative stress, we have demonstrated that changes observed in
      cytoskeleton of Sertoli cells under these conditions were protective, and seem to
      be an adaptive phenomenon against a pro-oxidant environment resulting from
      retinol treatment. We have hypothesized that the cytoskeleton can conduct
      electrons through actin microfilaments, which would be a natural process
      necessary for cell homeostasis. In the present study we demonstrate results
      correlating retinol metabolism, actin architecture, mitochondria physiology and
      ROS, in order to demonstrate that the electron conduction through actin
      microfilaments might explain our results. We believe that electrons produced by
      retinol metabolism are dislocated through actin microfilaments to mitochondria,
      and are transferred to electron transport chain to produce water. When
      mitochondria capacity to receive electrons is overloaded, superoxide radical
      production is increased and the oxidative stress process starts. Our results
      suggested that actin cytoskeleton is essential to oxidative stress production
      induced by retinol treatment, and electrons conduction through actin
      microfilaments can be the key of this correlation.

PMID- 17203243
TI  - Effect of bilateral in vivo ischemia/reperfusion on the activities of superoxide
      dismutase and catalase: response to a standardized grape suspension.
AB  - PURPOSE: Ischemia/reperfusion (I/R) is a major etiological factor in the bladder
      dysfunctions observed in men with lower tract obstruction, women with
      postmenopausal incontinence and with aging. A standardized grape suspension
      protects the rabbit urinary bladder from both the contractile dysfunctions and
      the morphologic changes mediated by I/R. Using a model of in vivo bilateral
      ischemia/reperfusion, the current study investigated the effect of this grape
      suspension on the endogenous antioxidant defense systems. MATERIALS AND METHODS:
      24 NZW rabbits were separated into 6 groups of 4. Groups 1-3 were treated by
      gavage with aqueous grape suspensions; groups 4-6 received sugar-water vehicle.
      Groups 3 and 6 were controls. Groups 1 and 4 were subjected to bilateral ischemia
      for 2 h (I). Groups 2 and 5 underwent bilateral ischemia for 2 h and reperfusion
      for 1 week (I/R). For all rabbit bladders, the muscle and mucosa were separated
      by blunt dissection and analyzed separately. The effects of the various
      treatments on bladder antioxidant systems of cytoplasmic superoxide dismutase (Cu
      Zn superoxide dismutase; SOD), and catalase (CAT) were evaluated. RESULTS: The
      standardized grape suspension up-regulated both SOD and CAT activity of bladder
      muscle and mucosa in control animals. There were few differences in the grape
      suspension treated animals after ischemia, and in general the activities
      decreased following I/R. CONCLUSIONS: Increases of SOD and CAT activity in
      control animals as a result of grape suspension suggest a greater antioxidant
      capacity. This increase in the antioxidant defense system may explain the
      increased protection of grape suspension in the face of ischemia and I/R.
      However, the activities of both enzyme systems decreased in the smooth muscle
      subjected to I/R showing that reperfusion damages these systems probably via
      oxidation damage to the enzymes themselves.

PMID- 17203242
TI  - Gene expression profiles of endothelial progenitor cells by oligonucleotide
      microarray analysis.
AB  - Among the many tissue stem or progenitor cells recently being unveiled,
      endothelial progenitor cells (EPCs) have attracted particular attention, not only
      because of their cardinal role in vascular biology and embryology but also
      because of their potential use in the therapeutic development of a variety of
      postnatal diseases, including cardiovascular and peripheral vascular disorders
      and cancer. The aim of this study is to provide some basic and comprehensive
      information on gene expression of EPCs to characterize the cells in molecular
      terms. Here, we focus on EPCs derived from CD34-positive mononuclear cells of
      human umbilical cord blood. The EPCs were purified and expanded in culture and
      analyzed by a high-density oligonucleotide microarray and real-time RT-PCR
      analysis. We identified 169 up-regulated and 107 down-regulated genes in the EPCs
      compared with three differentiated endothelial cells of human umbilical vein
      endothelial cells (HUVEC), human lung microvascular endothelial cells (LMEC) and
      human aortic endothelial cells (AoEC). It is expected that the obtained list
      include key genes which are critical for EPC function and survival and thus
      potential targets of EPC recognition in vivo and therapeutic modulation of
      vasculogenesis in cancer as well as other diseases, in which de novo
      vasculogenesis plays a crucial role. For instance, the list includes Syk and
      galectin-3, which encode protein tyrosine kinase and beta-galactoside-binding
      protein, respectively, and are expressed higher in EPCs than the three control
      endothelial cells. In situ hybridization showed that the genes were expressed in
      isolated cells in the fetal liver at E11.5 and E14.5 of mouse development.

PMID- 17203244
TI  - The development of young siblings of children with autism from 4 to 54 months.
AB  - Cognitive and language skills of 39 siblings of children with autism (SIBS-A) and
      39 siblings of typically developing children (SIBS-TD) at ages 4, 14, 24, 36, and
      54 months were compared. Twelve of the 39 SIBS-A revealed a delay in cognition
      and/or language (including one child diagnosed with autism) compared to only two
      SIBS-TD. Developmental trajectories revealed that the cognitive differences
      disappeared by age 54 months, but some differences in language ability remained.
      Thus, most SIBS-A were well-functioning, but some revealed cognitive and/or
      language difficulties during the preschool years. Even these siblings by and
      large caught up by the age of 54 months, with receptive and expressive language
      abilities remaining an area of difficulty for some earlier identified siblings.

PMID- 17203246
TI  - Regulation of calnexin sub-cellular localization modulates endoplasmic reticulum
      stress-induced apoptosis in MCF-7 cells.
AB  - The endoplasmic reticulum (ER) is the cellular compartment where proteins enter
      the secretory pathway, undergo post-translational modifications and acquire a
      correct conformation. If these functions are chronically altered, specific ER
      stress signals are triggered to promote cell death through the intrinsic
      apoptotic pathway. Here, we show that tunicamycin causes significant alteration
      of calnexin sub-cellular distribution in MCF-7 cells. Interestingly, this
      correlates with the absence of both tunicamycin-induced calnexin phosphorylation
      as well as tunicamycin-induced cell death. Under these conditions, calnexin
      associated Bap31, an ER integral membrane protein, is subjected to a caspase-8
      cleavage pattern within a specific sub-compartment of the ER. These results
      suggest that MCF-7 resistance to ER stress-induced apoptosis is partially
      mediated by the expression level of calnexin which in turn controls its sub
      cellular localization, and its association with Bap31. These data may delineate a
      resistance mechanism to the ER stress-induced intrinsic apoptotic pathway.

PMID- 17203245
TI  - Cardiac glycoside induces cell death via FasL by activating calcineurin and NF
      AT, but apoptosis initially proceeds through activation of caspases.
AB  - Decrease in caspase activity is a common phenomenon in drug resistance. For
      effective therapeutic intervention, detection of such agents, which affects other
      pathway independent of caspases to promote cell death, might be important.
      Oleandrin, a polyphenolic glycoside induced cell death through activation of
      caspases in a variety of human tumour cells. In this report we provide evidence
      that besides caspases activation, oleandrin interacts with plasma membrane,
      changes fluidity of the membrane, disrupts Na(+)/K(+)-ATPase pump, enhances
      intracellular free Ca(2+) and thereby activates calcineurin. Calcineurin, in
      turns, activates nuclear transcription factor NF-AT and its dependent genes such
      as FasL, which induces cell death as a late response of oleandrin. Cell death at
      early stages is mediated by caspases where inhibitors partially protected
      oleandrin-mediated cell death in vector-transfected cells, but almost completely
      in Bcl-xL-overexpressed cells. Overall, our data suggest that oleandrin might be
      important therapeutic molecule in case of tumors where cell death pathway occurs
      due to deregulation of caspase-mediated pathway.

PMID- 17203249
TI  - Archaeometry, an interdisciplinary approach.

PMID- 17203247
TI  - Attenuation of genotoxicity under adhesion-restrictive conditions through
      modulation of p53, gamma H2AX and nuclear DNA organization.
AB  - Interactions between tumor cells and their substratum influence cancer
      progression by modulating cell proliferation and survival. We now investigated
      whether signaling responses to UV irradiation differ on adhesion-permissive or
      restrictive substrates. The latter conditions diminished spreading and
      proliferation of neo 6.3/C8161 melanoma in which metastasis is suppressed by
      introduction of neo-tagged chromosome 6, but permitted proliferation of human
      metastatic C8161 melanoma. Apoptosis-associated PARP cleavage and DNA
      fragmentation induced by UV irradiation were diminished on the restrictive
      substrate in C8161 melanoma. Genotoxic responses to UV irradiation like
      persistent increases in the phosphorylation of histone H2AX, induction of the
      tumor suppressor p53 protein and greater binding of this protein to its DNA
      consensus sequence, were all decreased on the restrictive substrate. The latter
      also promoted a 2 fold increase of DNA condensation in chromatin and enhanced
      activation of the survival - and invasion-associated MMP-9 gelatinase B,
      preferentially in metastatic C81261 melanoma. Our data suggest that adaptation to
      restrictive substrates in metastatic C8161 melanoma decreases UV-induced
      apoptosis, partly through attenuation of DNA damage signaling responses and
      changes in genomic organization.

PMID- 17203248
TI  - Use of the diffusive gradients in thin films technique to evaluate (bio)available
      trace metal concentrations in river water.
AB  - Concentrations of Cd, Cu, Cr, Pb, Ni and Zn were monitored in the Svitava River
      (the Czech Republic) during April and September 2005. Total concentrations and
      total dissolved concentrations were obtained through regular water sampling, and
      the diffusive gradients in thin films technique (DGT) were used to gain
      information on the kinetically labile metal concentrations. Each measured
      concentration was compared with the corresponding average (bio)available
      concentration calculated from the mass of metal accumulated by the moss species
      Fontinalis antipyretica. The concentrations of Cd, Pb, Cr and Zn measured using
      DGT corresponded well with those obtained after the deployment of Fontinalis
      antipyretica moss bags in the Svitava River, but the concentrations of Cu and Ni
      did not. The calculated (bio)available Cu concentration correlated well with the
      total dissolved concentration of Cu, whereas no correlation was found to exist
      between the concentrations of Ni.

PMID- 17203250
TI  - Multivariate curve resolution of rapid-scan FTIR difference spectra of quinone
      photoreduction in bacterial photosynthetic membranes.
AB  - Photosynthetic reaction centres and membranes are systems of particular interest
      and are often taken as models to investigate the molecular mechanisms of selected
      bioenergetic reactions. In this work, a multivariate curve resolution by
      alternating least squares procedure is detailed for resolution of time-resolved
      difference FTIR spectra probing the evolution of quinone reduction in
      photosynthetic membranes from Rhodobacter sphaeroides under photoexcitation. For
      this purpose, different data sets were acquired in the same time range and
      spectroscopic domain under slightly different experimental conditions. To enable
      resolution and provide meaningful results the different data sets were arranged
      in an augmented matrix. This strategy enabled recovery of three different species
      despite rank-deficiency conditions. It also results in better definition
      (identity and evolution) of the contributions. From the resolved spectra, the
      species have been attributed to: 1. the formation of ubiquinol, more precisely
      the disappearance of Q/appearance of QH(2); 2. conformational change of the
      protein in the surrounding biological medium; 3. oxidation of diaminodurene, a
      redox mediator. Because, moreover, results obtained from augmented data sets
      strategies enable quantitative and qualitative interpretation of concentration
      profiles, other effects, for example the consequence of repeated light excitation
      of the same sample, choice of illumination power, or the number of spectra
      accumulated could be compared and discussed.

PMID- 17203253
TI  - Laser interference-based techniques and applications in structural inspection of
      works of art.
AB  - Techniques based on laser interferometry principles provide great potential to
      retrieve imperceptible bulk information regarding the physical and mechanical
      condition of complex and inhomogeneous structures. This review presents the
      progress in and prospects for optical coherent interferometry techniques in
      artwork conservation applications, in particular concerning the performance of
      the developed instrumentations and methodologies. Each of the state-of-the-art
      techniques is introduced by reference to fundamental principles, basic equations
      and general optical geometry. In this context, a brief introduction to
      fundamental principles governing the optical coherent interferometry measurements
      is presented prior to discussion on performance. Some exemplary results
      demonstrating that bulk interferometric signals can be obtained from rough
      artwork surfaces are shown and their suitability is reviewed. Several
      opportunities for art conservation research and applications are summarised and
      discussed.

PMID- 17203251
TI  - Sensitive and selective determination of glutathione in probiotic bacteria by
      capillary electrophoresis-laser induced fluorescence.
AB  - Glutathione (GSH) is a thiol with an important function in protecting tissue
      against the oxidative stress which has been related to carcinogenesis in the
      colon. For this reason the development of probiotic species producing glutathione
      could be of great interest. To determine the glutathione content of some
      probiotic bacteria of the Bifidobacterium and Lactococcus genera, a very
      sensitive and selective analytical method based on capillary electrophoresis
      coupled to laser-induced fluorescence detection has been developed. Pretreatment
      of cell-lysate samples is very simple--precipitation of protein with acetonitrile
      in 1:2 volume ratio. The fluorophore 5-iodoacetamidofluorescein (5-IAF) was
      chosen for glutathione derivatisation; it reacts with thiols at pH 12.5, forming
      a fluorescent adduct which is excited by a laser at 488 nm for detection. The
      reaction conditions optimised were temperature, time, and 5-IAF/GSH molar ratio.
      Electrophoresis was performed with a carbonate buffer (25 mmol L(-1), pH 9.8) as
      background electrolyte and a voltage of 30 kV; an electrophoretic run was
      complete in less than 7 min. There was a good linear relationship between
      concentration and response in the range 2.5-500 ng mL(-1) and the LOD was 0.5 ng
      mL(-1). The glutathione content of probiotic cells was determined by using the
      standard additions method to reduce matrix effects. The method was fully
      validated and shown to be of suitable sensitivity and selectivity for
      determination of GSH in probiotic cell lysates.

PMID- 17203252
TI  - NADH screen-printed electrodes modified with zirconium phosphate, Meldola blue,
      and Reinecke salt. Application to the detection of glycerol by FIA.
AB  - Bulk screen-printed electrodes (bSPEs) modified with zirconium phosphate (ZrP)
      and Meldola blue (MB) and by electrochemical deposition of a Reineckate film
      (bMBZrPRs-SPEs) have been constructed and used as NADH sensors. Cyclic
      voltammetric investigation of these bulk electrochemically modified screen
      printed electrodes revealed stable catalytic activity in oxidation of the reduced
      form of the coenzyme nicotinamide adenine dinucleotide (NADH). Flow-injection
      analysis (FIA) coupled with amperometric detection confirmed the improved
      stability of the bMBZrPRs-SPEs (10(-4) mol L(-1) NADH, %RSD = 4.2, n = 90, pH
      7.0). Other conditions, for example applied working potential (+50 mV relative to
      Ag|AgCl), flow rate (0.30 mL min(-1)) and pH-dependence (range 4.0-10.0) were
      evaluated and optimized. A glycerol biosensor, prepared by immobilizing glycerol
      dehydrogenase (GDH) on the working electrode area of a bMBZrPRs-SPE, was also
      assembled. The biosensor was most stable at pH 8.5 (%RSD = 5.6, n = 70, 0.25 mmol
      L(-1) glycerol). The detection and quantification limits were 2.8 x 10(-6) and
      9.4 x 10(-6) mol L(-1), respectively, and the linear working range was between
      1.0 x 10(-5) and 1.0 x 10(-4) mol L(-1). To assess the effect of interferences,
      and recovery by the probe we analyzed samples taken during fermentation of
      chemically defined grape juice medium and compared the results with those
      obtained by HPLC.

PMID- 17203254
TI  - Removal of pharmaceutical residues in a pilot wastewater treatment plant.
AB  - Concern is growing over the contamination of the environment with pharmaceutical
      residues, among which non-steroidal anti-inflammatory drugs (NSAIDs) are one of
      the most abundant groups. Their widespread appearance in the aquatic environment
      is because of their high consumption and their incomplete removal during
      wastewater treatment. Because effective operation of wastewater-treatment plants
      is important for minimising the release of xenobiotic compounds, for example
      pharmaceutical products, into the aquatic environment, our study focuses on
      removal of commonly used NSAIDs (ibuprofen, naproxen, ketoprofen, diclofenac) and
      clofibric acid in a specially designed small-scale pilot wastewater treatment
      plant (PWWTP). This study shows that, except for diclofenac, steady-rate removal
      of NSAIDs over a two-year monitoring period has been achieved. Elimination of the
      compounds in the PWWTP was >or=87% for ibuprofen, naproxen and ketoprofen but
      only 49-59% for diclofenac. We also studied clofibric acid. Results after one
      month of operation revealed 30% elimination with no sign of adaptation by the
      biomass. Also described are degradation products of diclofenac, which we were
      able to identify because of the similarity of their mass spectra with those in
      the NIST library and by comparing the retention times of different compounds.
      Although the structures of these compounds were confirmed with a high probability
      (99%), we still need to compare the fragmentation of authentic compounds with
      degradation products formed under our experimental conditions. Degradation
      products of ibuprofen, naproxen, ketoprofen, and clofibric acid were found but
      these must be identified by use of high-resolution mass spectrometry and analysis
      of authentic compounds.

PMID- 17203255
TI  - Recently developed GC/MS and LC/MS methods for determining NSAIDs in water
      samples.
AB  - Pharmaceuticals have become major targets in environmental chemistry due to their
      presence in aquatic environments (following incomplete removal in wastewater
      treatment or point-source contaminations), threat to drinking water sources and
      concern about their possible effects to wildlife and humans. Recently several
      methods have been developed for the determination of drugs and their metabolites
      in the lower nanogram per litre range, most of them using solid-phase extraction
      (SPE) or solid-phase microextraction (SPME), derivatisation and finally gas
      chromatography mass spectrometry (GC-MS), gas chromatography tandem mass
      spectrometry (GC-MS/MS) and liquid chromatography electrospray tandem mass
      spectrometry (LC-ES/MS/MS). Due to the elevated polarity of non-steroidal anti
      inflamatory drugs (NSAIDs), analytical techniques based on either liquid
      chromatography coupled to mass spectrometry (LC-MS) and gas chromatography
      coupled to mass spectrometry (GC-MS) after a previous derivatisation step are
      essential. The most advanced aspects of current GC-MS, GC-MS/MS and LC-MS/MS
      methodologies for NSAID analysis are presented.

PMID- 17203256
TI  - Determination of five nitrobenzoic acids in groundwater by solid-phase extraction
      and liquid chromatography-mass spectrometry.
AB  - A method involving solid-phase extraction (SPE) and reversed-phase liquid
      chromatography-mass spectrometry (LC-MS) has been developed for determination, in
      groundwater, of nitrobenzoic acids associated with 2,4,6-trinitrotoluene
      production. Pre-concentration on a co-polymer-based SPE cartridge enabled
      quantitative extraction of the analytes from water. Investigation of negative ion
      electrospray and atmospheric-pressure chemical ionization mass spectrometry
      indicated the sensitivity of APCI was more than twice that of ESI. An 15N-labeled
      internal standard was used to achieve more accurate quantitation and mass
      assignment. Recovery was better than 80% when 10 mL water was extracted with the
      SPE cartridge. Combination of SPE with LC-MS analysis resulted in method
      detection limits of less than 5 microg L-1. The method has been used for analysis
      of groundwater samples collected from a site of a former ammunition plant.
      Contamination with nitrobenzoic acids was determined at microg L-1 levels.

PMID- 17203257
TI  - Fluorescence optosensing implemented with sequential injection analysis: a novel
      strategy for the determination of labetalol.
AB  - The coupling of sequential injection analysis and optosensing has been developed
      for the first time. It has been applied to the determination of labetalol in both
      pharmaceuticals and urine samples, with the analytical signal (native
      fluorescence) being monitored directly on sensing zone microbeads. The solid
      support used was the nonionic silica gel C18, using 20% methanol-water (v:v) as a
      carrier. By using a 1.5-ml sample volume, we achieved a detection limit of 3.3 ng
      ml-1. This sensitivity allowed the determination of the compound in urine
      samples. A recovery study was carried out at the labetalol levels usually found
      in urine after pharmaceuticals administration, and recovery percentages close to
      100% were obtained. The relative standard deviation was 3.4% for 100 ng ml-1
      labetalol. No pretreatment was needed for urine samples, only an appropriate
      dilution, therefore minimizing the time required per sample analysis. In
      addition, the determination of the analyte was also carried out in one
      pharmaceutical, with a satisfactory result being obtained.

PMID- 17203258
TI  - The certification of a nominal 20 micromol/mol H2S/N2 standard reference material
      using two independent methods.
AB  - To support federal, state and local regulations on the amount of hydrogen sulfide
      (H(2)S) released into the atmosphere, the National Institute of Standards and
      Technology (NIST) has certified standard reference material (SRM) 2731 Hydrogen
      Sulfide in Nitrogen (nominal amount-of-substance fraction 20 micromol/mol H(2)S).
      Since it was first produced and certified in 1989, NIST has certified four
      separate lots of this SRM. In each case, the value assignment of the lot
      concentration was accomplished by comparison to a permeation tube-generated
      calibration curve. For the certification of the new lot, two independent methods
      were used to value-assign the concentration. In addition to the permeation tube
      method, a second method involving the dynamic dilution of a high-concentration
      gravimetrically prepared primary standard mixture containing H(2)S/N(2) was also
      used. Agreement between the two methods was 0.10% and the total uncertainty
      assigned to the lot concentration was 1.35% (relative).

PMID- 17203259
TI  - Recent advances in surface plasmon resonance based techniques for bioanalysis.
AB  - Surface plasmon resonance (SPR) is a powerful and versatile spectroscopic method
      for biomolecular interaction analysis (BIA) and has been well reviewed in
      previous years. This updated 2006 review of SPR, SPR spectroscopy, and SPR
      imaging explores cutting-edge technology with a focus on material, method, and
      instrument development. A number of recent SPR developments and interesting
      applications for bioanalysis are provided. Three focus topics are discussed in
      more detail to exemplify recent progress. They include surface plasmon
      fluorescence spectroscopy, nanoscale glassification of SPR substrates, and
      enzymatic amplification in SPR imaging. Through these examples it is clear to us
      that the development of SPR-based methods continues to grow, while the
      applications continue to diversify. Major trends appear to be present in the
      development of combined techniques, use of new materials, and development of new
      methodologies. Together, these works constitute a major thrust that could
      eventually make SPR a common tool for surface interaction analysis and
      biosensing. The future outlook for SPR and SPR-associated BIA studies, in our
      opinion, is very bright. Surface plasmon resonance (SPR) is a powerful and
      versatile spectroscopic method for biomolecular interaction analysis (BIA) and
      has been well reviewed in previous years. This updated 2006 review of SPR, SPR
      spectroscopy, and SPR imaging explores cutting-edge technology with a focus on
      material, method, and instrument development. A number of recent SPR developments
      and interesting applications for bioanalysis are provided. Three focus topics are
      discussed in more detail to exemplify recent progress. They include surface
      plasmon fluorescence spectroscopy, nanoscale glassification of SPR substrates,
      and enzymatic amplification in SPR imaging. Through these examples it is clear to
      us that the development of SPR-based methods continues to grow, while the
      applications continue to diversify. Major trends appear to be present in the
      development of combined techniques, use of new materials, and development of new
      methodologies. Together, these works constitute a major thrust that could
      eventually make SPR a common tool for surface interaction analysis and
      biosensing. The future outlook for SPR and SPR-associated BIA studies, in our
      opinion, is very bright.

PMID- 17203261
TI  - Arsine and selenium hydride trapping in a novel quartz device for atomic
      absorption spectrometry.
AB  - A novel quartz device has been designed to trap arsine and selenium hydride and
      subsequently to volatilize the collected analyte and atomize it for atomic
      absorption spectrometric detection. The device is actually the multiple
      microflame quartz-tube atomizer (multiatomizer) with inlet arm modified to serve
      as the trap and to accommodate the oxygen-delivery capillary used to combust
      hydrogen during the trapping step. The effect of relevant experimental conditions
      (trap temperature during trapping and hydrogen flow rate and trap temperature
      during volatilization) on collection and volatilization efficiency was
      investigated. Under the optimum conditions collection and volatilization
      efficiency for arsenic and selenium were 50 and 70%, respectively.

PMID- 17203262
TI  - A feasibility study on the use of visible and short wavelengths in the near
      infrared region for the non-destructive measurement of wine composition.
AB  - The aim of this study was to explore the capability of spectroscopy in the
      visible (Vis) and short wavelength near-infrared (NIR) regions for the non
      destructive measurement of wine composition in intact bottles. In this study we
      analysed a wide range of commercial wines obtained in Australia in different
      types of bottles (e.g. colours, diameters and heights), including different wine
      styles and varieties. Wine bottles were scanned in the Vis-NIR region (600-1,100
      nm) in a monochromator instrument in transflectance mode. Principal component
      analysis (PCA) and partial least-squares (PLS) regression were used to interpret
      the spectra and develop calibrations for wine composition. Due to the relatively
      small number of samples available full cross-validation (leave-one-out) was used
      as validation. The coefficient of correlation in calibration [Formula: see text]
      and the standard error of cross-validation (SECV) were 0.67 (SECV: 0.48%), 0.83
      (SECV: 4.01 mg L-1), 0.70 (SECV: 28.6 mg L-1) and 0.50 (SECV: 0.15) for alcohol
      content, total SO2, free SO2 and pH, respectively, in the set of wine samples
      analysed. These preliminary results showed that the assessment of wine
      composition by Vis and short wavelengths in the NIR is possible for either
      qualitative analysis (e.g. low-, medium- and high-quality grading), or for
      screening of composition during bottling and storage. Although low accuracy and
      precision were obtained for the chemical parameters routinely analysed in wine,
      calibration models for the chemical parameters were considered acceptable for
      screening purposes in terms of the standard errors obtained.

PMID- 17203263
TI  - Micellar solid-phase microextraction for determining partition coefficients of
      substituted polycyclic aromatic hydrocarbons in micellar media: possible
      prediction of hydrocarbon-micelle behaviour.
AB  - Micellar solid-phase microextraction (MSPME) coupled to gas chromatography-mass
      spectrometry (GC-MS) has been used to obtain partition coefficients of a group of
      18 substituted aromatic hydrocarbons to ionic and nonionic micelles. Statistical
      and factor analyses have been utilized to establish some general equations
      relating molecular descriptors of non-substituted polycyclic aromatic
      hydrocarbons and their partition coefficients obtained by MSPME. The obtained
      equations have correlation coefficients higher than 0.94. They are used to
      predict hydrocarbon-micelle partition coefficients for a group of hydrocarbons
      with reported literature values giving a correlation coefficient of 0.98 and a
      standard deviation of the prediction of 0.182. The predictive model was also
      applied to substituted polycyclic aromatic hydrocarbons with partition
      coefficient values obtained by MSPME, with a 69% level of success.

PMID- 17203264
TI  - Fluorescent sensing layer for the determination of L-malic acid in wine.
AB  - An enzymatic method for determining L-malic acid in wine based on an L-malate
      sensing layer with nicotinamide adenine dinucleotide (NAD+), L-malate
      dehydrogenase (L-MDH) and diaphorase (DI), immobilized by sol-gel technology, was
      constructed and evaluated. The sol-gel glass was prepared with tetramethoxysilane
      (TMOS), water and HCl. L-MDH catalyzes the reaction between L-malate and NAD+,
      producing NADH, whose fluorescence (lambdaexc=340 nm, lambdaem=430 nm) could be
      directly related to the amount of L-malate. NADH is converted to NAD+ by applying
      hexacyanoferrate(III) as oxidant in the presence of DI. Some parameters affecting
      sol-gel encapsulation and the pH of the enzymatic reaction were studied. The
      sensing layer has a dynamic range of 0.1-1.0 g/L of L-malate and a long-term
      storage stability of 25 days. It exhibits acceptable reproducibility [sr(%)
      approximately 10] and allows six regenerations. The content of L-malic acid was
      determined for different types of wine, and polyvinylpolypyrrolidone (PVPP) was
      used as a bleaching agent with red wine. The results obtained for the wine
      samples using the sensing layer are comparable to those obtained from a reference
      method based on UV-vis molecular absorption spectrometry, if the matrix effect is
      corrected for.

PMID- 17203265
TI  - Room-temperature, phosphorimetric determination of the beta-blocking agent
      pindolol in pharmaceutical tablets, urine and blood serum.
AB  - It is already recognised that heavy-atom-induced, room-temperature
      phosphorescence can be used to determine pindolol in pharmaceutical samples and
      biological fluids. We describe here a new, simple, rapid and selective
      development of this technique. The phosphorescence signals derive from the
      interaction of pindolol with a relatively high concentration of heavy-atom salts
      in the presence of sodium sulphite as oxygen scavenger. Phosphorescence was
      registered in the presence of 1.2 M potassium iodide, 15 mM sodium sulphite and
      30% v/v methanol at 450 nm, exciting at 285 nm. The detection limit was 21.1 ng
      mL(-1). The method has been successfully applied to the determination of pindolol
      in commercial pharmaceutical tablets, urine and blood serum.

PMID- 17203266
TI  - [Palliative therapy concepts for patients with urothelial cancer of the urinary
      bladder].
AB  - Urothelial carcinoma usually occurs in older patients. At initial diagnosis,
      about 30% of all patients show muscle invasive tumor growth or metastases. Due to
      their advanced clinical stage, palliative therapy concepts become more and more
      interesting. Gross and intractable hematuria can be treated with special bladder
      irrigation or selective arterial embolization. Hydronephrosis can be treated in
      the long-term with self-expanding memotherm stents. Palliative pelvic radiation
      is still controversial.

PMID- 17203268
TI  - Development of a content-valid standardized orthopedic assessment tool (SOAT).
AB  - INTRODUCTION: Content validation of an instrument that measures student
      performance in OSCE-type practical examinations is a critical step in a tool's
      overall validity and reliability [Hopkins (1998), Educational and Psychological
      Measurement and Evaluation (8th ed.). Toronto: Allyn & Bacon]. PURPOSE: The
      purpose of the paper is to outline the process employed to create a content-valid
      Standardized Orthopedic Assessment Tool (SOAT). Orthopedic assessment skills are
      employed by athletic therapists, physiotherapists and physicians. All follow very
      similar diagnostic algorithms and that system was used to develop the original
      SOAT [Cyriax (1982). Textbook of Orthopaedic Medicine, (vol. 1) Bailliere
      Tindall]. METHODS: To validate the tool, the study followed procedures outlined
      by Violato, Salami, and Muiznieks (2002), Journal of Manipulative Physiological
      Therapeutics, 25, 111-115, and Butterwick, Paskevich, Vallevand and Lafave
      (2006), Journal of Allied Health: a modified Ebel procedure. An expert group of
      athletic therapists from across Canada were chosen to create the content valid
      tool. Representation from all accredited athletic therapy programs in Canada was
      sought. Experts participated in three stages of content validation: Stage one
      consisted of individuals grading tasks on difficulty (hard, medium, easy) and
      importance (essential, important, not important) for 8 body regions (cervical
      spine, lumbar spine, shoulder, elbow, wrist/hand/thumb, hip, knee and lower
      leg/foot/ankle) and three diagnoses for each body region (24 total). If 80%
      consensus was not achieved in the first stage, then in stage two, face to face
      discussion is meant to clarify positions and achieved consensus, if possible.
      RESULTS: The history component, the observation component, scanning exams,
      clearing joints above and below the lesion site and active range of motion,
      passive range of motion and isometric resisted testing all yielded 80% consensus
      in the first two stages of development. A third stage was added to this process
      because a new model of measurement was conceptualized during the second stage due
      to a lack of consensus on two orthopedic assessment categories: special testing
      and palpation. The new model consisted of a ;;clinical reasoning" metric that
      tied each section of an orthopedic assessment (history; observation; scanning and
      clearing; examination, special testing; palpation; conclusion) together and would
      permit the expert rater to evaluate the student performance based on the
      student's rationale for tests chosen rather than the traditionally rigid
      checklists. At least 80% consensus was achieved with the new ;;clinical
      reasoning" metric and the originally contentious special testing and palpation
      categories. CONCLUSIONS: The new SOAT that underwent content validation may be a
      hybrid between the traditional OSCE-type checklists and global scales that
      provide a more realistic and thus more valid depiction of orthopedic assessment
      clinical competence. Now that content validation has been established, the next
      steps include inter-rater reliability testing.

PMID- 17203267
TI  - [Options in palliative therapy for penile cancer].
AB  - Penile cancer, with an incidence of 0.1-0.9/100,000 males/year, is one of the
      least common malignant tumors. Most patients are over 50 years old and the tumor
      is slow growing. Therapeutic success is highly dependent on lymph node status.
      Cancer related death is usually due to local complications such as arrosion
      bleeding caused by the tumor or infected inguinal metastases. The therapy for
      advanced penile cancer and its complications represents a challenge. Taking into
      consideration quality of life, the therapeutic strategy should be based on the
      patient's age, his sexual function, motivation and psychological condition, as
      well as previous illnesses and tumor biology. Palliative therapy requires good
      interdisciplinary work between oncologists, radiologists, plastic surgeons,
      physiotherapists and psychologists.

PMID- 17203269
TI  - How do medical teachers address the problem of transfer?
AB  - Clinical teachers often complain that medical students have forgotten or somehow
      "lost" knowledge that has been taught at pre-clinical levels at the time of
      entering the clinical part of education. The purpose of this qualitative study
      was to explore, whether transfer of knowledge was identified as a problem by the
      teaching staff of anatomy and surgery, and if so, what strategies they used to
      overcome it. Semi-structured interviews were conducted with ten medical teachers
      in anatomy and surgery. Most teachers recognised that there was a problem of
      transfer and some individuals had adopted strategies to address this. However,
      there was no formal educational strategy suggested to overcome the problem of
      transfer. The conclusion is that transfer needs to be addressed both by basic
      science teachers and clinical teachers. There is a need for a mutual educational
      discourse of the contexts students will face.

PMID- 17203270
TI  - A biomechanical analysis of the self-retaining pedicle hook device in posterior
      spinal fixation.
AB  - Regular hooks lack initial fixation to the spine during spinal deformity surgery.
      This runs the risk of posterior hook dislodgement during manipulation and
      correction of the spinal deformity, that may lead to loss of correction, hook
      migration, and post-operative junctional kyphosis. To prevent hook dislodgement
      during surgery, a self-retaining pedicle hook device (SPHD) is available that is
      made up of two counter-positioned hooks forming a monoblock posterior claw
      device. The initial segmental posterior fixation strength of a SPHD, however, is
      unknown. A biomechanical pull-out study of posterior segmental spinal fixation in
      a cadaver vertebral model was designed to investigate the axial pull-out strength
      for a SPHD, and compared to the pull-out strength of a pedicle screw. Ten porcine
      lumbar vertebral bodies were instrumented in pairs with two different
      instrumentation constructs after measuring the bone mineral density of each
      individual vertebra. The instrumentation constructs were extracted employing a
      material testing system using axial forces. The maximum pull-out forces were
      recorded at the time of the construct failure. Failure of the SPHD appeared in
      rotation and lateral displacement, without fracturing of the posterior
      structures. The average pull-out strength of the SPHD was 236 N versus 1,047 N in
      the pedicle screws (P < 0.001). The pull-out strength of the pedicle screws
      showed greater correlation with the BMC compared to the SPHD (P < 0.005). The
      SPHD showed to provide a significant inferior segmental fixation to the posterior
      spine in comparison to pedicle screw fixation. Despite the beneficial
      characteristics of the monoblock claw construct in a SPHD, that decreases the
      risk of posterior hook dislodgement during surgery compared to regular hooks, the
      SPHD does not improve the pull-out strength in such a way that it may provide a
      biomechanically solid alternative to pedicle screw fixation in the posterior
      spine.

PMID- 17203271
TI  - "Juxtafacet cysts", a misleading name for cystic formations of mobile spine
      (CYFMOS).
AB  - To present 58 cystic space-occupying formations of the spinal canal in 53 cases;
      these formations are called "juxtafacet cysts". Fifty-Three patients (33 women
      and 20 men, with an average age of 60.8 years) were evaluated retrospectively by
      neurosurgery. All of the patients had received simple X-P, computed tomography
      (CT) and magnetic resonance imaging (MRI) before surgery. The neurological
      findings were evaluated on admission and in a follow-up review. Surgical
      intervention was performed on all patients and they underwent gross-total cyst
      removal. During surgery, the origin of a cyst was well observed. Follow-up data
      ranged from 6 to 46 months. Patient outcome was graded on a scale of excellent,
      good, or poor. Histological findings were evaluated. In 53 patients 58 cysts were
      identified. Four of the patients had multiple cysts. All cysts were associated
      with mobile spine. Fifty-five cysts were found in the lumbo-sacral region, two
      cysts were found in the cervico-thoracic region and one cyst in the thoracic
      region. Forty-two patients presented back pain and 52 patients presented
      radicular pain. Four patients had a cauda equina syndrome. Sensory disturbance
      was observed in 24 cases and motor weakness was observed in 21 cases.
      Claudication was observed in 19 cases. All cases with cervico-thoracic or
      thoracic cysts presented myelopathy. The duration of these clinical symptoms
      ranged from 10 days to 10 years. After surgery there was no case of a recurrent
      cyst during the follow-up period. Thirty-four cases had an excellent outcome, 18
      a good outcome, and one a poor outcome. Out of 58 cysts 32 were joint cysts (11
      synovial cysts, 21 ganglion cysts). A further 19 were flavum cysts, one was a
      posterior longitudinal ligament (PLL) cyst and six others were unknown pseudo
      cysts. In 34 of the cysts we found hemosiderin deposits and in eight amyloid
      deposits. Present investigation and findings in literature show a clear
      comparison of these cystic formations and the mobile part of the spine. An
      anatomical relation to a vertebral joint ("facet") is only found in some of the
      cases (32 of 58). Further to that, the name "cyst" is not correct either, because
      most of the cystic formations are presented without a cell lining on their
      internal wall and therefore they are pseudo-cystic. We think that these cystic
      formations should be called "cystic formations of mobile spine" (CYFMOS) rather
      than "juxtafacet cysts". A surgical intervention is the best treatment for these
      cysts if they cause a compression of nerve roots or/and of the spinal cord.

PMID- 17203272
TI  - Modified transcorporeal anterior cervical microforaminotomy for cervical
      radiculopathy: a technical note and early results.
AB  - A prospective analysis of the first twenty patients operated for cervical
      radiculopathy by a new modification of transcorporeal anterior cervical
      foraminotomy technique. To evaluate early results of a functional disc surgery in
      which decompression for the cervical radiculopathy is done by drilling a hole in
      the upper vertebral body and most of the disc tissue is preserved. Earlier
      approaches to cervical disc surgery either advocated simple discectomy or
      discectomy with fusion, ultimately leading to loss of motion segment. Posterior
      foraminotomy does not address the more common anterior lesion. Twenty patients
      suffering from cervical radiculopathy not responding to conservative treatment
      were chosen for the new technique. Upper vertebral transcorporeal foraminotomy
      was performed with the modified technique in all the patients. All the patients
      experienced immediate/early relief of symptoms. No complications of vertebral
      artery injury, Horner's syndrome or recurrent laryngeal nerve palsy were noted.
      Modified transcorporeal anterior cervical microforaminotomy is an effective
      treatment for cervical radiculopathy. It avoids unnecessary violation of the disc
      space and much of the bony stabilizers of the cervical spine. Short-term results
      of this technique are quite encouraging. Longer-term analysis can help in
      outlining the true benefits of this technique.

PMID- 17203273
TI  - Quantitative analysis of sensory functions after lumbar discectomy using current
      perception threshold testing.
AB  - A Neurometer device is an electrical nerve stimulator used to determine the
      current perception threshold (CPT) evoked by stimulating A-beta fibers at 2,000
      Hz, A-delta fibers at 250 Hz and C fibers at 5 Hz. CPT evaluation is used for
      analyzing peripheral nerve dysfunction. In this study, the sensory disturbance of
      the lower-extremity was quantitatively analyzed using CPT testing before and
      after lumbar discectomy. In 33 patients (L4/5: 16 and L5/S: 17), as subjective
      evaluations, tactile sensation and leg pain were assessed before and 2 weeks
      after surgery. In the subjectively improved group (n = 22), significant decreases
      in CPT at 2,000 and 250 Hz were noted postoperatively, whereas in the unchanged
      group (n = 11), no significant changes in CPT at any frequencies was noted. The
      leg pain improved in all patients. Likewise, CPT at 5 Hz, which stimulated C
      fiber, decreased significantly for both improved and unchanged groups. CPT
      measured by a Neurometer is very useful in assessing lower-extremity sensory
      functions before and after surgery for lumbar disc herniation.

PMID- 17203275
TI  - Prospective study of standalone balloon kyphoplasty with calcium phosphate cement
      augmentation in traumatic fractures (G. Maestretti et al.).

PMID- 17203274
TI  - Pedicle morphology of the thoracic spine in preadolescent idiopathic scoliosis:
      magnetic resonance supported analysis.
AB  - Although several studies have been reported on the adult vertebral pedicle
      morphology, little is known about immature thoracic pedicles in patients with
      idiopathic scoliosis. A total of 310 pedicles (155 vertebrae) from T1 to T12 in
      10-14 years age group were analyzed with the use of magnetic resonance imaging
      and digital measurement program in 13 patients with right-sided thoracic
      idiopathic scoliosis. Each pedicle was measured in the axial and sagittal planes
      including transverse and sagittal pedicle width and angles, chord length,
      interpedicular distance and epidural space width on convex and concave sides of
      the curve. The smallest transverse pedicle widths were in the periapical region
      and the largest were in the caudal region. No statistically significant
      difference in transverse pedicle widths was detected between the convex and
      concave sides. The transverse pedicle angle measured 15.56 degrees at T1 and
      decreased to 6.32 degrees at T12. Chord length increased gradually from the
      cephalad part of the thoracic spine to the caudad part as the shortest length was
      seen at T1 convex level with a mean of 30.45 mm and the largest length was seen
      at T12 concave level with a mean of 41.73 mm. The width of epidural space on the
      concave side was significantly smaller than that on the convex side in most
      levels of the curve. Based on the anatomic measurements, it may be reasonable to
      consider thoracic pedicle screws in preadolescent idiopathic scoliosis.

PMID- 17203276
TI  - Paraspinal muscle control in people with osteoporotic vertebral fracture.
AB  - The high risk of sustaining subsequent vertebral fractures after an initial
      fracture cannot be explained solely by low bone mass. Extra-osseous factors, such
      as neuromuscular characteristics may help to explain this clinical dilemma.
      Elderly women with (n = 11) and without (n = 14) osteoporotic vertebral fractures
      performed rapid shoulder flexion to perturb the trunk while standing on a flat
      and short base. Neuromuscular postural responses of the paraspinal muscles at T6
      and T12, and deep lumbar multifidus at L4 were recorded using intramuscular
      electromyography (EMG). Both groups demonstrated bursts of EMG that were
      initiated either before or shortly after the onset of shoulder flexion (P <
      0.05). Paraspinal and multifidus onset occurred earlier in the non-fracture group
      (50-0 ms before deltoid onset) compared to the fracture group (25 ms before and
      25 ms after deltoid onset) in the flat base condition. In the short base
      condition, EMG amplitude increased significantly above baseline earlier in the
      non-fracture group (75-25 ms before deltoid onset) compared to the fracture group
      (25-0 ms before deltoid onset) at T6 and T12; yet multifidus EMG increased above
      baseline earlier in the fracture group (50-25 ms before deltoid) compared to the
      non-fracture group (25-0 ms before deltoid). Time to reach maximum amplitude was
      shorter in the fracture group. Hypothetically, the longer time to initiate a
      postural response and shorter time to reach maximum amplitude in the fracture
      group may indicate a neuromuscular contribution towards subsequent fracture
      aetiology. This response could also be an adaptive characteristic of the central
      nervous system to minimise vertebral loading time.

PMID- 17203277
TI  - A survey of the "medical" articles in the European Spine Journal, 2006.

PMID- 17203278
TI  - Growth parameters in maternal uniparental disomy 7 and 14.
AB  - INTRODUCTION: Growth retardation has been reported in most cases of maternal
      uniparental disomy (UPD) 7 and 14, but has never been evaluated in a systematic
      approach. In this study, an analysis is presented of the auxological data from
      the literature at birth and on the occasion of the last evaluation of 34 cases
      with maternal UPD 7 (21 heterodisomy, 13 isodisomy) and 29 cases with maternal
      UPD 14 (22 heterodisomy, 7 isodisomy). For maternal UPD 7, statistical analysis
      revealed that length and weight at birth as well as on the occasion of the last
      evaluation were strongly below average (-2.94 SD and -2.62 SD, and -3.39 SD and 
      3.11 SD, respectively), whereas at both evaluations occipitofrontal head
      circumference (OFC) was only slightly below the average (-1.00 SD and -0.85 SD).
      For maternal UPD 14 at birth, growth retardation is rather concordant for length,
      weight, and OFC (-2.78 SD, -2.84 SD, and -1.69 SD). Later in life body mass index
      (BMI) is above average (1.06 SD) and continuously increasing before and after
      puberty (-0.58 SD and 2.07 SD). CONCLUSION: Growth retardation and relative
      macrocephaly are of prenatal onset and still present in adults with maternal UPD
      7. For patients with maternal UPD 14, growth curves for height, BMI and OFC
      differ strongly. Genomic imprinting might be a major causative factor, but it
      seems to function differently for maternal UPD 7 and maternal UPD 14.

PMID- 17203279
TI  - Influence of maternal smoking on neonatal aortic intima-media thickness, serum
      IGF-I and IGFBP-3 levels.
AB  - Epidemiological studies have reported associations between a range of
      cardiovascular risk factors such as smoking and intima-media thickness (IMT).
      Some reports indicate that the maternal tobacco smoking causes disturbances of
      the endocrine status of the foetus. There are several potential mechanisms by
      which insulin-like growth factor I (IGF-I) could modify atherosclerotic processes
      either locally or in a systemic manner. The aim of this study was to investigate
      the influence of maternal smoking on neonatal aortic IMT (aIMT), serum IGF-I and
      IGF-binding protein-3 (IGFBP-3) levels. Aortic intima-media thickness was
      measured in 28 neonates whose mothers smoked during the pregnancy and 28 control
      neonates. Mean and weight-adjusted aIMT were significantly greater in the
      neonates whose mothers smoked (0.455 +/- 0.009 mm and 0.151 +/- 0.005 mm/kg,
      respectively) than in controls (0.403 +/- 0.029 mm and 0.118 +/- 0.014 mm/kg,
      respectively). Birth-weight of newborns whose mothers smoked was less than that
      of the controls. The decreases in serum IGF-I and IGFBP-3 observed in the infants
      whose mothers smoked were non-significant. Mean aIMT was negatively associated
      with birth-weight and IGF-I level. In conclusion, neonates whose mothers smoked
      have significantly increased aIMT. It might play a role in the pathogenesis of
      atherosclerosis in adult life.

PMID- 17203280
TI  - Heme oxygenase-1 expression in premature and mature neonates during the first
      week of life.
AB  - Newborns are exposed to mechanical and oxidative stress during labor and to
      relative hyperoxia thereafter during the course of adaptation to the extrauterine
      conditions. Part of the adaptation mechanism is the rapid degradation of fetal
      hemoglobin and the oxidation of its heme moiety by heme oxygenases (HOs). Heme
      oxygenase-1 enzyme (HO-1) is the inducible isoform, which is induced by and
      protective against oxidative stress. We hypothesized that HO-1 may play a role in
      the physiological adaptation of newborns. We therefore measured the HO-1 mRNA
      expression with cRT-PCR during the first week after birth in healthy mature and
      premature newborns. We found that HO-1 was induced until day 2 or 3 after birth,
      but its level had dropped below the birth HO-1 mRNA level by the end of the first
      week. HO-1 levels and inducibility were similar in mature newborns and premature
      newborns. The fact that HO-1 was inducible even in gestation week 26 suggests
      that HO-1 plays an important role in the early adaptation processes.

PMID- 17203282
TI  - Chorioretinal lesions as the unique feature of complete chronic granulomatous
      disease in an 8-year-old girl.

PMID- 17203283
TI  - Superficial acral fibromyxoma of the toe, with erosion of the distal phalanx. A
      clinical report.
AB  - Superficial acral fibromyxoma (SAFM) is a rare soft tissue tumor most often
      located in the ungual region of the fingers and toes. This tumor was first
      described in 2001, and since then very few cases have been reported. We present
      the case of a 35-year-old male with a SAFM located in the toe, with involvement
      of the nail and erosion of the distal phalanx. The lesion was surgically removed,
      and the histopathological study confirmed the diagnosis of SAFM. The differential
      diagnosis must be established with other myxoid tumors and with those lesions
      showing a predilection for the distal portions of the limbs. After 2 years, the
      patient remains disease free, with no disability of any kind.

PMID- 17203281
TI  - Analgesia in preterm newborns: the comparative effects of sucrose and glucose.
AB  - The aim of this study was to evaluate the effectiveness of different oral
      carbohydrate solutions for alleviation of pain in healthy preterm babies. Thirty
      one preterm infants who were having blood drawn by heel prick were given 2 ml of
      solution A (20% sucrose), solution B (20% glucose) or solution C (placebo,
      sterile water) into the mouth, 2 min before lancing. Behavioural responses to
      this painful stimulus were measured by duration of crying and facial expressions
      (Neonatal Facial Coding System, NFCS) and physiological responses were measured
      by heart rate (HR), respiratory rate (RR), and oxygen saturation changes
      (SaO(2)). Infants had a mean birth weight (+/-SD) of 1,401 g (406), gestational
      age of 30.5 weeks (2.7); at the time of the procedure the postmenstrual age was
      32.3 weeks (1.5). There was no significant difference in the time spent squeezing
      the heel between the three groups (P = 0.669). After the heel prick of both the
      sucrose and glucose groups the duration of first cry and total crying time was
      significantly reduced (P = 0.005 and P = 0.007). When the babies received placebo
      they showed a significantly higher NFCS score at 4 and 5 min after the heel prick
      (P = 0.009 and 0.046 respectively). Following painful stimulus HR increased
      significantly in the first 3 min compared with baseline, and at the first minute
      the mean of the HR was found to be significantly higher in the placebo group than
      in the sucrose and glucose groups (P = 0.007). We concluded that both sucrose and
      glucose administered orally before a heel prick reduce the pain response in
      preterm infants.

PMID- 17203284
TI  - Low-grade central osteosarcoma mimicking fibrous dysplasia: a report of two
      cases.
AB  - Low-grade central osteosarcoma is an unusual variant of conventional
      osteosarcoma. We present here two rare cases of low-grade central osteosarcoma
      resembling fibrous dysplasia. A 24-year-old woman diagnosed as fibrous dysplasia
      was treated with intra-lesional excision and curettage of the tumor but tumor
      recurred at 4 months after surgery. Distal femoral en-bloc resection was
      performed followed by arthroplasty with mega-prosthesis of the knee. A 57-year
      old man diagnosed as central osteosarcoma was treated with wide excision of the
      tumor, followed by reconstruction with the vascularized fibula graft combined
      with an autogenous irradiated bone graft. Because of the difficulty in
      distinguishing low-grade central osteosarcoma from a benign lesion, open biopsy
      is needed to obtain a large tumor sample. Careful clinical and pathological
      evaluation is required to obtain a definite diagnosis. The treatment of low-grade
      central osteosarcoma is en-block resection with wide surgical margins.

PMID- 17203285
TI  - Effects of diclofenac and tenoxicam on distraction osteogenesis.
AB  - INTRODUCTION: In the management of bone defects, pseudoarthrosis, deformities,
      chronic osteomyelitis and in extremity lengthening procedures, the technique of
      distraction osteogenesis (DO) has been frequently used. In this experimental
      animal study, the effects of two non-steroidal anti-inflammatory drugs, i.e.,
      diclofenac and tenoxicam, on the outcomes of distraction osteogenesis are
      investigated. MATERIALS AND METHODS: In this study, 30 mature New Zealand-type
      male rabbits (2.5-4.5 kg) were used. The rabbits were randomized into three
      groups, each consisting of ten animals. Under optimal operating conditions, a pre
      reconstructed circular external fixator was applied on the right tibias of
      rabbits, and osteotomy was performed with a Gigli saw just below the tibial
      tuberosity. After seven postoperative days, distraction was initiated at a rhythm
      of 2 x 0.5 mm/day. During the 10 days of distraction, adjunctive therapy was not
      instituted for group I (control group). For 10 days, group II received i.m.
      diclofenac sodium (0.5 mg/kg per day) and group III was treated with tenoxicam (8
      mg/kg per day i.m.). At the end of 3 weeks postoperatively, five rabbits from
      each group were killed for histologic examinations. The remaining rabbits were
      killed at the end of eight postoperative weeks for biomechanical and histological
      analysis. Besides, radiological examinations were performed at the end of 3, 6
      and 8 weeks postoperatively for the radiologic evaluation of calluses. For
      statistical evaluations between groups, Kruskal-Wallis variance analysis, and for
      intergroup assessments, Mann-Whitney test were performed. RESULTS: For
      radiological evaluations, the scoring system developed by Lane and Sandhu, and
      for histopathological assessments, the grading system of Huddlestone et al. were
      used. Biomechanical tests were realized using torsional loading. During the first
      3 weeks, the groups did not differ much in the radiological parameters. However,
      in the diclofenac group and in especially the tenoxicam group, the histological
      scores were lower than in the control group. Radiological images obtained at the
      end of 6 weeks demonstrated inadequate consolidation in the diclofenac and
      tenoxicam groups when compared with the control group. At the end of 8 weeks
      postoperatively, in consideration of biomechanical, radiological and histological
      tests, significantly worse regenerates were obtained in the diclofenac and
      tenoxicam groups. CONCLUSIONS: During the distraction osteogenesis period,
      diclofenac and tenoxicam affected the quality of regenerate unfavorably. This
      effect is sustained during all periods of bone healing. However, this finding
      should be supported by experimental and human studies.

PMID- 17203286
TI  - Molecular features of astrovirus associated with a gastroenteritis outbreak in an
      aged-care centre.
AB  - The study presented here was conducted in order to gain a better understanding of
      the role of astroviruses (AsVs) in outbreaks of gastroenteritis among the
      elderly. This report is the first to provide detailed information on the
      molecular characteristics of an AsV causing an outbreak in an aged-care centre
      and is the first to clearly establish that individuals infected in such an
      outbreak were, in fact, elderly. The outbreak under investigation took place in
      Victoria, Australia, in October 2005. Twelve individuals (mean age +/- standard
      deviation [SD] 85.5 +/- 12.3 years) became ill during the outbreak from a total
      population of 86 susceptible residents. The mean duration (+/-SD) of illness was
      2.3 +/- 1.6 days; symptoms included diarrhoea, abdominal pain, nausea and
      headache. No bacterial pathogens were detected. AsV was identified in five faecal
      specimens using electron microscopy and reverse transcription-polymerase chain
      reaction methodologies; no other gastroenteritis virus was detected. Nucleotide
      sequence analysis indicated the AsV identified could be assigned to the 1d
      lineage of AsV serotype 1 and that the AsV was not a recombinant form. The
      findings, taken together with previous work, indicate the AsV serotype most
      commonly associated with gastroenteritis outbreaks among the elderly is serotype
      1 AsV.

PMID- 17203287
TI  - Increased incidence of Lyme borreliosis following mild winters and during warm,
      humid summers.

PMID- 17203289
TI  - [On the 150th birthday of Cesar Roux (1857-1918). Memories of the life and work
      of an important pupil of Kocher].
AB  - Cesar Roux was one of the few universal surgeons at the end of the 19th century
      who dominated all fields of surgery and influenced current surgery with his
      innovative spirit. Pioneering spirit and the story of the success of modern
      surgery are linked with his name. On the occasion of his 150th birthday, we
      recall the memory of this great surgeon. The personality and the history of
      Professor Cesar Roux form a part of our medical and surgical heritage.

PMID- 17203290
TI  - Association of interleukin (IL)-4 intron-3 and IL-6 -174 G/C gene polymorphism
      with susceptibility to end-stage renal disease.
AB  - Earlier studies suggest that end-stage renal disease (ESRD) is associated with
      inflammatory state and have become a major cause of morbidity and mortality
      worldwide. This study speculated the role of interleukins (IL)-2, -4, and -6
      cytokines gene polymorphism with risk of susceptibility to ESRD. Polymorphism in
      IL-2 (-330 T/G, polymerase chain reaction [PCR]-restriction fragment length
      polymorphism), IL-4 (intron-3, variable number of tandem repeat, variable number
      tandem repeats analysis), and IL-6 (-174 G/C, amplification refractory mutation
      system, i.e. ARMS-PCR) were genotyped in 193 ESRD patients and 180 controls.
      Significant difference was observed in genotype frequencies of IL-4 and IL-6
      between ESRD patients and control group (p<0.001 and p=0.032, respectively).
      Patients had higher frequency of homozygous B2B2 genotype (IL-4) than controls
      (62.7% vs 46.7) and GG genotype of IL-6 (73.1% vs 60.6%). The genotypic
      frequencies of IL-2 were comparable in patients and controls (p=0.102).
      Significant association of IL-4 was also observed in patients with
      glomerulonephritis (p=0.001). Combination of low IL-4 and high IL-6 genotypes
      were significantly associated with ESRD showing the highest risk, i.e.
      >threefolds risk (odds ratio=3.48, 95%CI=1.88-6.42; p < 0.001) among the four
      possible combinations taking high IL-4 and low IL-6 as reference. Our study
      suggests that polymorphism in IL-4 and IL-6 may be associated with susceptibility
      to ESRD. Further, combined analysis implicated a higher risk in ESRD patients
      with low IL-4 and high IL-6 producing genotypes. This study provided the basis
      for defined anti-inflammatory approaches to limit renal disease progression.

PMID- 17203288
TI  - Functional contribution of the endothelial component to the vasorelaxing effect
      of resveratrol and NS 1619, activators of the large-conductance calcium-activated
      potassium channels.
AB  - Large-conductance calcium-activated potassium channels (BK) of smooth muscle play
      a role in the relevant modulation of vascular tone, due to their calcium- and
      voltage-dependent mechanisms of activation. A potential role of endothelial BK
      channels has also been suggested by approaches on endothelial cell cultures.
      However, no functional study, aimed at evaluating the contribution of endothelial
      BK channels to the effect of BK-openers, has been reported. Resveratrol and NS
      1619, BK-openers, have been tested on endothelium-intact and -denuded aortic
      rings. Furthermore, the effects of high depolarisation of potassium channel
      blockers TEA (Tetraethylammonium), 4-AP ( 4-Aminopyridine) and IbTX (Iberiotoxin)
      and of inhibitors of NO-pathway (L-NAME and ODQ) have been evaluated. The
      presence of endothelium increased the vasorelaxing potency of BK-openers. This
      potentiation was eliminated by L-NAME and ODQ. TEA, 4-AP, IbTX and high
      depolarisation had modest or no antagonist influence on resveratrol in
      endothelium-denuded aortic rings. The effects of NS 1619 on endothelium-denuded
      aortic rings were not affected by IbTX, and were modestly antagonised by TEA, 4
      AP and high depolarisation. In intact endothelium vessels, TEA, IbTX and 4-AP
      antagonised the vasorelaxing effect of the two BK-activators. A BK-mediated
      release of endothelial NO seems a very important factor, determining a strong
      influence on vasodilator profile of BK-openers. Therefore, an eventual therapy
      with a BK-opener could promote a series of cardiovascular impacts not confined to
      the only direct vasorelaxing effects, but also due to a significant contribution
      of endothelial NO.

PMID- 17203291
TI  - Analysis of alpha-synuclein, dopamine and parkin pathways in neuropathologically
      confirmed parkinsonian nigra.
AB  - The identification of mutations that cause familial Parkinson's disease (PD)
      provides a framework for studies into pathways that may be perturbed also in the
      far more common, non-familial form of the disorder. Following this hypothesis, we
      have examined the gene regulatory network that links alpha-synuclein and parkin
      pathways with dopamine metabolism in neuropathologically verified cases of
      sporadic PD. By means of an in silico approach using a database of eukaryotic
      molecular interactions and a whole genome transcriptome dataset validated by qRT
      PCR and histological methods, we found parkin and functionally associated genes
      to be up-regulated in the lateral substantia nigra (SN). In contrast, alpha
      synuclein and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene expression
      levels were significantly reduced in both the lateral and medial SN in PD. Gene
      expression for Septin 4, a member of the GTP-binding protein family involved in
      alpha-synuclein metabolism was elevated in the lateral parkinsonian SN.
      Additionally, catalase and mitogen-activated protein kinase 8 and poly(ADP
      ribose) polymerase family member 1 (PARP1) known to function in DNA repair and
      cell death induction, all members of the dopamine synthesis pathway, were up
      regulated in the lateral SN. In contrast, two additional PD-linked genes,
      glucocerebrosidase and nuclear receptor subfamily 4, group A, member 2 (NR4A2)
      showed reduced expression. We show that in sporadic PD, parkin, alpha-synuclein
      and dopamine pathways are co-deregulated. Alpha-synuclein is a member of all
      three gene regulatory networks. Our analysis results support the view that alpha
      synuclein has a central role in the familial as well as the non-familial form of
      the disease and provide steps towards a pathway definition of PD.

PMID- 17203292
TI  - Absolute bioavailability and metabolism of omeprazole in relation to CYP2C19
      genotypes following single intravenous and oral administrations.
AB  - OBJECTIVE: The aim of this study was to evaluate the absolute bioavailability and
      the metabolism of omeprazole following single intravenous and oral
      administrations to healthy subjects in relation to CYP2C19 genotypes. METHODS:
      Twenty subjects, of whom 6 were homozygous extensive metabolizers (hmEMs), 8 were
      heterozygous EMs (htEMs) and 6 were poor metabolizers (PMs) for CYP2C19, were
      enrolled in this study. Each subject received either a single omeprazole 20 mg
      intravenous dose (IV) or 40 mg oral dose (PO) in a randomized fashion during 2
      different phases. RESULTS: Mean omeprazole AUC (0,infinity) was 1164, 3093 and
      10511 ng h/mL after PO, and 1435, 2495 and 6222 ng h/mL after IV in hmEMs, htEMs
      and PMs, respectively. Therefore, the absolute bioavailability of omeprazole in
      PMs was significantly higher than that in hmEMs (p < 0.001) and htEMs (p <
      0.001). Hydroxylation metabolic indexes after IV and PO were significantly lower
      in PMs than in hmEMs (p < 0.001) and htEMs (p < 0.001), and was correlated with
      the absolute bioavailability (p < 0.0001 for both IV and PO). Sulfoxidation
      metabolic index after IV was significantly different between the CYP2C19
      genotypes, whereas no difference was found after a single oral dose. CONCLUSION:
      This study indicates that the absolute bioavailability of omeprazole differs
      among the three different CYP2C19 genotypes after a single dose of omeprazole
      orally or intravenously. Hydroxylation metabolic index of omeprazole may be
      mainly attributable to the genotype of CYP2C19. As for the sulfoxidation
      metabolic index after a single oral dose, intestinal CYP3A may be contributed to
      omeprazole metabolism.

PMID- 17203293
TI  - Atypical lung involvement in a patient with systemic juvenile xanthogranuloma.
AB  - Juvenile xanthogranuloma (JXG) is a non-Langerhans cell histiocytosis
      characterized by xanthoma-like cutaneous lesions. It is a benign condition that
      is generally asymptomatic. Visceral involvement is uncommon, but when present may
      occur in various locations and in different combinations. Pulmonary involvement
      has been reported as bilateral, multiple micro- or macronodular lesions. We
      present a 10-year-old boy with systemic (skin, lung, liver and kidney) JXG who
      showed lung involvement with mainly an interstitial pattern. Bilateral multiple
      micronodules in both lungs and mediastinal adenopathy were also present.

PMID- 17203294
TI  - Pleurodesis for effusions in pediatric oncology patients at end of life.
AB  - BACKGROUND: Pleurodesis for end-of-life care has been used in adults for decades,
      but little is known about the usefulness of this technique in improving the
      quality of care for pediatric patients. OBJECTIVE: To assess whether intractable
      pleural effusions in pediatric oncology patients at end of life could be
      sufficiently relieved by pleurodesis. MATERIAL AND METHODS: Eleven pleurodeses
      were performed with doxycycline in seven pediatric cancer patients (age 3-21
      years) with intractable pleural effusions at the end of life. Five patients had
      unilateral pleurodeses and two had a unilateral followed by bilateral
      pleurodeses. RESULTS: Respiratory rates decreased in all seven patients (P =
      0.016) and aeration improved significantly after chest tube placement (P =
      0.033). The chest tubes were placed a median of 1 day before pleurodesis. Eight
      of nine chest tubes (89%) were removed before discharge at a median of 3 days
      after pleurodesis. Pain secondary to the pleurodesis lasted 1 day or less.
      Improvement in the respiratory rate remained after pleurodesis and chest tube
      removal (P = 0.031). Five of seven patients (70%) were able to leave the hospital
      to return home. The five patients discharged lived 10 to 49 days (median 19 days)
      after discharge. CONCLUSION: Pediatric oncology patients with intractable
      effusions at end of life can have respiratory benefit from pleurodeses and, as a
      result, are more likely to return home for terminal care.

PMID- 17203295
TI  - Right-sided superior vena cava draining into the left atrium: a rare anomaly of
      systemic venous return.
AB  - The most commonly encountered systemic thoracic venous anomaly is a persistent
      left superior vena cava that drains into the right atrium via the coronary sinus.
      A much rarer systemic venous anomaly is that of isolated anomalous drainage of a
      normally positioned right superior vena cava (RSVC) into the left atrium (LA).
      This has been reported in approximately 20 patients with the diagnosis usually
      being made by cardiac catheterization. We report the case of a toddler with
      asymptomatic hypoxemia resulting from anomalous drainage of a normal RSVC into
      his LA. This was diagnosed non-invasively by contrast-enhanced chest CT.

PMID- 17203296
TI  - A double-chambered right ventricle with Behcet disease: case report.

PMID- 17203297
TI  - Long-term benefit of radon spa therapy in the rehabilitation of rheumatoid
      arthritis: a randomised, double-blinded trial.
AB  - This study investigates the effects of radon (plus CO2) baths on RA in contrast
      to artificial CO2 baths in RA rehabilitation using a double-blinded trial
      enrolling 134 randomised patients of an in-patient rehabilitative programme
      (further 73 consecutive non-randomised patients are not reported here). The
      outcomes were limitations in occupational context/daily living (main outcome),
      pain, medication and further quantities. These were measured before the start,
      after the end of treatment and quarterly in the year thereafter. Repeated
      measures analysis of covariance (RM-ANCOVA) of the intent-to-treat population was
      performed with group main effects (GME) and group x course interactions (G x C)
      reported. Hierarchically ordered hypotheses ensured the adherence of the nominal
      significance level. The superiority of the radon treatment was found regarding
      the main outcome (RM-ANCOVA until 12 months: p(GME) = 0.15, p(G x C) = 0.033).
      Consumption of steroids (p(GME) = 0.064, p(G x C) = 0.025) and NSAIDs (p(GME) =
      0.035, p(G x C) = 0.008) were significantly reduced. The results suggest
      beneficial long-term effects of radon baths as adjunct to a multimodal
      rehabilitative treatment of RA.

PMID- 17203298
TI  - Surgical treatment of type II floating knee: comparisons of the results of type
      IIA and type IIB floating knee.
AB  - The prognosis of type II floating knee injuries was not as good as that of type
      I. Our purpose is to clarify the factors affecting the outcome of type II
      floating knee injuries. Thirty-five patients (36 limbs) with type II floating
      knee injury were studied with a mean follow-up of 52 months (26-96). Blake and
      McBryde had classified these injuries into type I for pure diaphyseal (true type)
      fracture and type II if the intra-articular involvements are one or more
      including hip, knee and ankle joints (variant type). According to this
      classification, we divided these patients into two groups depending on whether
      their knees were involved or not. Those cases with intra-articular knee
      involvement were classified as type IIA, while those without intra-articular knee
      involvement were classified as type IIB. Of the 36 cases, 21 were classified as
      type IIA and 15 were type IIB. The functional outcomes of these injuries were
      evaluated by using the criteria of Karlstrom and Olerud and analyzed with
      multivariate analysis. After multivariate analysis with logistic regression, we
      show the following results: first, the poor functional outcome of type II
      floating knee is contributed by type IIA. Second, the type IIA group has severer
      femoral open fracture grading (P = 0.027) and poorer functional outcome (P =
      0.009) than type IIB. Third, the significant contributing factors to final
      outcome are the group (P = 0.013) and the fixation time after injury in femur (P
      = 0.015). Intra-articular knee involvement is the most important factor
      contributing to poor outcome of type II floating knee. The treatment of floating
      knee injuries with intra-articular knee involvement is still difficult. Further
      efforts to search better methods of treatment are required for these complex
      injuries in the future.

PMID- 17203299
TI  - Prediction of recovery from a post-traumatic coma state by diffusion-weighted
      imaging (DWI) in patients with diffuse axonal injury.
AB  - INTRODUCTION: To determine whether diffusion-weighted magnetic resonance (MR)
      imaging findings combined with initial clinical factors indicate the depth of
      shearing lesions in the brain structure and therefore relate to coma duration in
      diffuse axonal injury (DAI). METHODS: A total of 74 adult patients (48 male and
      26 female) with DAI were examined with conventional MR imaging and diffusion
      weighted MR imaging between 2 hours and 20 days after injury. Apparent diffusion
      coefficient (ADC) maps were obtained and the mean ADC values of each region of
      interest (ROI) were measured using MRI console software. The involvement of the
      brainstem, deep gray matter, and corpus callosum was determined for each sequence
      separately as well as for the combination of all sequences. The correlations
      between MR imaging findings indicating the presence of apparent brain injury
      combined with initial clinical factors were determined. RESULTS: Clinical
      characteristics, such as initial score on the Glasgow coma scale (GCS), age and
      number of all lesions, and ADC scores were predictive of the duration of coma.
      CONCLUSION: It was possible to predict post-traumatic coma duration in DAI from
      cerebral MR imaging findings combined with clinical prognostic factors in the
      acute to subacute stage after head injury. Age, ADC scores, GCS score and number
      of lesions were highly significant in predicting coma duration. The technique
      presented here might provide a tool for in vivo detection of DAI to allow the
      prediction of the coma duration during the early stages in patients with
      traumatic brain injury.

PMID- 17203301
TI  - A gene responsible for Ghosal hemato-diaphyseal dysplasia maps to chromosome 7q33
      34.
AB  - Ghosal hemato-diaphyseal dysplasia is a rare autosomal recessive disorder
      characterized by a progressive sclerosing diaphyseal dysplasia and refractory
      anemia. The pathogenesis and genetic bases of this syndrome remain hitherto
      unknown. We have performed a genome wide search in two inbred families
      originating from Algeria and Tunisia. Here, we report on the mapping of a disease
      gene to chromosome 7q33-34 (Zmax = 4.21 at theta = 0 at locus D7S2513) in a 3.4
      Mb defined by loci D7S2560 and AC091742. Ongoing studies will hopefully lead to
      identification of the disease-causing gene.

PMID- 17203300
TI  - Evidence in favor of linkage to human chromosomal regions 18q, 5q and 13q for
      bicuspid aortic valve and associated cardiovascular malformations.
AB  - The aim of this study was to identify regions of the genome that harbor genes
      influencing inheritance of bicuspid aortic valve (BAV) and/or associated
      cardiovascular malformation (CVM). Aortic valve disease is an important clinical
      problem, which often results in valve replacement, the second most common cardiac
      surgery in the United States. In every age group, a majority of cases of valve
      disease involves a BAV. BAV is the most common CVM with a reported prevalence of
      1-2%. Heritability studies indicate that BAV determination is almost entirely
      genetic. We used a family-based genome-wide linkage analysis with microsatellite
      markers. Parametric and nonparametric analyses were performed with the software
      GENEHUNTER and SOLAR (Sequential Oligogenic Linkage Analysis Routines). Thirty
      eight families (353 subjects) with BAV and/or associated CVM were assessed. Each
      participant underwent a standardized echocardiographic examination. The highest
      LOD score, 3.8, occurred on chromosome 18q between markers D18S68 and D18S1161.
      Two other chromosomal regions, 5q15-21 (between D5S644 and D5S2027) and 13q33
      qter (between D13S1265 and 13qter), exhibited suggestive evidence of linkage (LOD
      > 2.0). Further, two previously reported linkage peaks on 9q34 and 17q24 were
      replicated in family specific analyses. No significant X chromosome linkage peaks
      were identified. In this genome-wide scan we demonstrate for the first time, that
      BAV and/or associated CVM exhibit linkage to chromosomes 18q, 5q and 13q. These
      regions likely contain genes whose mutation results in BAV and/or associated CVM
      indicating their important role in valvulogenesis and cardiac development.

PMID- 17203302
TI  - Segregation analysis of 1,546 prostate cancer families in Finland shows recessive
      inheritance.
AB  - Prostate cancer (PCa) is the most frequently diagnosed cancer in men worldwide
      and is likely to be caused by a number of genes with different modes of
      inheritance, population frequencies and penetrance. The objective of this study
      was to assess the familial aggregation of PCa in a sample of 1,546 nuclear
      families ascertained through an affected father and diagnosed during 1988-1993,
      from the unique, founder population-based resource of the Finnish Cancer
      Registry. Segregation analysis was performed for two cohorts of 557 early-onset
      and 989 late-onset families evaluating residual paternal effects and assuming
      that age at diagnosis followed a logistic distribution after log-transformation.
      The results did not support an autosomal dominant inheritance as has been
      reported in many of the hospital-based prostatectomy series. Instead, it
      confirmed the existence of hereditary PCa in the Finnish population under a
      complex model that included a major susceptibility locus with Mendelian recessive
      inheritance and a significant paternal regressive coefficient that is indicative
      of a polygenic/multifactorial component. The strengths of our study are the
      homogenous Finnish population, large epidemiological population-based data,
      histologically confirmed cancer diagnosis done before the PSA-era in Finland and
      registry based approach. Our results support the evidence that the inheritance of
      PCa is controlled by major genes and are in line with the previous linkage
      studies. Moreover, this is the first time a recessive inheritance is suggested to
      fit PCa in all data even when divided to early and late-onset cohorts.

PMID- 17203303
TI  - PD-1 gene haplotype is associated with the development of type 1 diabetes
      mellitus in Japanese children.
AB  - Interaction between Programmed cell death-1 (PD-1), a member of costimulatory
      molecules, and its receptors Programmed cell Death-1 Ligand 1 (PD-L1) and
      Programmed cell Death-1 Ligand 2 (PD-L2), play an important role in the negative
      regulation of immune reactions. It was shown that a polymorphism in a regulatory
      site of the PD-1 gene was associated with susceptibility to several autoimmune
      diseases in various ethnic groups, whereas the contribution of the PD-1 gene or
      its ligand genes to the onset of type 1 diabetes (T1D) mellitus in the Japanese
      population remains unknown. We first screened PD-1, PD-L1, and PD-L2 genes for
      polymorphisms in the Japanese population, and then investigated the frequencies
      of polymorphisms in patients with T1D mellitus in comparison with healthy
      controls. In total, we identified 26 polymorphic sites within these genes, and
      then 23 polymorphisms with minor allele frequencies greater than 5% were
      intensively analyzed for genotyping in the patients and the controls. As a
      result, allele and genotype frequencies of the polymorphism numbers 2, 3, 4, 5,
      6, and 8 in the PD-1 gene were different to some extent between the patients and
      the controls with P < 0.05, which did not reach statistical significance after
      the correction of multiple comparisons. Allele or genotype frequencies of any
      SNPs in the PD-L1 or PD-L2 gene did not show differences between the patients and
      the controls. The frequencies of the estimated haplotypes, those of which
      consisted of polymorphism numbers 2, 3, 4, 5, 6, and 8 in the PD-1, were
      significantly different between the patients and the controls (P = 0.00095). The
      in vitro assessment for a transcription activity of each haplotype of the PD-1
      gene by luciferase assay did not demonstrate a functional difference between the
      haplotypes. In conclusion, the genetic evaluation by association study
      demonstrated that the PD-1 gene was a predisposing gene to the development of T1D
      mellitus in the Japanese population.

PMID- 17203305
TI  - Genetic variation in the base excision repair pathway and bladder cancer risk.
AB  - Genetic polymorphisms in DNA repair genes may impact individual variation in DNA
      repair capacity and alter cancer risk. In order to examine the association of
      common genetic variation in the base-excision repair (BER) pathway with bladder
      cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER
      genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1,
      and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional
      cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we
      estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age,
      gender, region and smoking status. SNPs in three genes showed significant
      associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1),
      the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap
      filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous
      variant for an OGG1 SNP in the promoter region (rs125701) had significantly
      decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78
      (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1
      rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk
      compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30
      (1.04-1.62), respectively. In summary, data from this large case-control study
      suggested bladder cancer risk associations with selected BER SNPs, which need to
      be confirmed in other study populations.

PMID- 17203306
TI  - Treatment of tripod fracture of zygomatic bone by N-2-butyl cyanoacrylate glue
      fixation, and its effects on the tissues.
AB  - The standard treatment of zygomatic bone fractures is fixation by microplates or
      miniplates and screws today. It is very difficult to place plates and screws into
      thin bones or small bone fragments especially in the facial bones and bones
      adjacent to important structures. Cyanoacrylate is used as a hemostatic agent, an
      embolic agent, in retinal tears, in corneal ulcers, in fixation of mandibular
      osteotomies and in craniofacial surgery. N-2-Butyl cyanoacrylate is a form of
      cyanoacrylate which is bioabsorbable and biocompatible. It is easily applied to
      the tissues. We aimed to determine the effect of N-2-butyl cyanoacrylate in the
      fixation of displaced zygomatic bone fractures. We examined the histotoxicity and
      the effects on healing and foreign body reaction of N-2-butyl cyanoacrylate.
      Eight New Zealand white rabbits underwent zygomatic osteotomies bilaterally. The
      fractures on left sides of the rabbits were determined as study site and right
      sides as control site. Knight and North classification of zygomatic bone
      fractures were used and group 4 fractures were made bilaterally. Open reduction
      of fractures was performed bilaterally and N-2-butyl cyanoacrylate was applied
      only on left sides. No fixation was made on right sides representing the control
      group. Postoperatively in the first, second, third and fourth weeks, two rabbits
      were sacrificed and the fracture sites were examined macroscopically and
      histopathologically. In the glued study group, fixation was obtained in all cases
      whereas in the control group, all the fractures were seen to be displaced. Tissue
      reaction was similar in the study and the control groups.

PMID- 17203304
TI  - Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the
      determination of platelet serotonin levels.
AB  - Autism is a neurodevelopmental disorder of unclear etiology. The consistent
      finding of platelet hyperserotonemia in a proportion of patients and its
      heritability within affected families suggest that genes involved in the
      serotonin system play a role in this disorder. The role in autism etiology of
      seven candidate genes in the serotonin metabolic and neurotransmission pathways
      and mapping to autism linkage regions (SLC6A4, HTR1A, HTR1D, HTR2A, HTR5A, TPH1
      and ITGB3) was analyzed in a sample of 186 nuclear families. The impact of
      interactions among these genes in autism was assessed using the multifactor
      dimensionality reduction (MDR) method in 186 patients and 181 controls. We
      further evaluated whether the effect of specific gene variants or gene
      interactions associated with autism etiology might be mediated by their influence
      on serotonin levels, using the quantitative transmission disequilibrium test
      (QTDT) and the restricted partition method (RPM), in a sample of 109 autistic
      children. We report a significant main effect of the HTR5A gene in autism (P =
      0.0088), and a significant three-locus model comprising a synergistic interaction
      between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010).
      In addition to the previously reported contribution of SLC6A4, we found
      significant associations of ITGB3 haplotypes with serotonin level distribution (P
      = 0.0163). The most significant models contributing to serotonin distribution
      were found for interactions between TPH1 rs4537731 and SLC6A4 haplotypes (P =
      0.002) and between HTR1D rs6300 and SLC6A4 haplotypes (P = 0.013). In addition to
      the significant independent effects, evidence for interaction between SLC6A4 and
      ITGB3 markers was also found. The overall results implicate SLC6A4 and ITGB3 gene
      interactions in autism etiology and in serotonin level determination, providing
      evidence for a common underlying genetic mechanism and a molecular explanation
      for the association of platelet hyperserotonemia with autism.

PMID- 17203307
TI  - Comparison between PET and PET/CT in recurrent head and neck cancer and clinical
      implications.
AB  - The aim of this retrospective study was to compare the diagnostic accuracy
      between positron emission tomography (PET) and combined PET/computed tomography
      (PET/CT) in the detection of recurrent head and neck squamous cell carcinoma
      (HNSCC) and to evaluate the degree of interobserver agreement. Thirty-two
      patients who had undergone curative treatment for HNSCC and who presented with a
      suspicion of recurrent local disease were studied with fluoro-2-deoxy-D-glucose
      (FDG)-PET imaging. All patients had undergone an inconclusive conventional workup
      (nasofibroscopy, CT scan and/or MRI). PET and PET/CT were reviewed by two nuclear
      medicine physicians independently. Performances of PET and PET/CT were compared
      using biopsy and/or clinical follow-up of at least 8 months as gold-standard. ROC
      curves were employed for statistical analysis. Out of 32 patients, 18 (56%) had a
      local recurrence. Intraclass correlation coefficients were strong (>90) and
      statistically significant (P < 0.0001) for the two reviewers in all cases. The
      sensitivity, specificity and accuracy of PET were found to be 94%, between 36 and
      50% and between 69 and 75%, respectively, depending on the consideration of
      equivocal cases. Results for PET/CT were found to be 94, 57 and 78%. The utility
      scores of PET and PET/CT were 0.72 and 0.78, respectively. PET/CT could have a
      direct impact on patient care with the avoidance of 8/14 (57%) unnecessary
      invasive procedures (panendoscopy under general anaesthesia). Combined PET/CT is
      more accurate than PET alone for detection of recurrent HNSCC. The findings of
      this study are reinforced by the strong interobserver agreement in the
      interpretation of the results.

PMID- 17203308
TI  - Salivary duct carcinoma in the sinonasal tract.
AB  - Salivary duct carcinoma (SDC) is an uncommon malignant tumor, characterized by
      aggressive behavior and poor prognosis. SDC usually arises from ductal epithelium
      of the major salivary glands, and it is quite infrequent elsewhere. We present a
      rare case of a 73-year-old man with SDC, which is possibly originated from the
      paranasal sinuses or the lacrimal system. Microscopic evaluation revealed that
      the tumor cells, with pleomorphic nuclei and abundant eosinophilic cytoplasm,
      formed cell nests and duct-like structure. A cribriform growth pattern was also
      seen. Immunohistochemical staining was positive for cytokeratins (CAM 5.2 and
      34betaE12), gross cystic disease fluid protein 15 (GCDFP-15), and androgen
      receptor protein, while p63 and involucrin were negative. The patient already had
      multiple metastasis of the tumor in the lung at diagnosis, and he could not
      undergo definitive surgical procedures, because of severe restrictive lung
      disease. Although SDC in the sinonasal tract is quite rare, SDC should be in the
      differential diagnosis in these regions, due to its aggressive behavior and poor
      prognosis.

PMID- 17203310
TI  - Endoscopic treatment of nasolacrimal sac obstruction secondary to fibrous
      dysplasia of paranasal sinuses.
AB  - Fibrous dysplasia involving paranasal sinuses mostly has asymptomatic features,
      but sometimes may cause signs and symptoms which relate to the location and
      extent of bony abnormalities. The use of endoscopic nasal surgery for debulking
      ethmoidal fibrous dysplasia, blocking the left nasolacrimal sac and simultaneous
      intranasal endoscopic dacryocystorhinostomy with silicone intubation is
      presented. The procedure and advantages of endoscopic approach over the external
      approach are outlined in this paper.

PMID- 17203309
TI  - Hyoid bone insertion tendinitis: clinicopathologic correlation.
AB  - Hyoid bone insertion tendinitis is often not taken into consideration in clinical
      practice and neglected in the differential diagnosis while evaluating patients
      with chronic neck pain. One of the main important reasons why physicians do not
      bear this entity in mind is that it has not been well described
      histopathologically. Two patients, who had been diagnosed and treated surgically
      for hyoid bone insertion tendinitis, were presented in this study.
      Microscopically, degenerative changes in the striated muscle tissue, which are
      characterized by myocyte necrosis, atrophy along with fibrosis and calcification
      in some foci, were observed. These findings provide evidence for the clinical
      picture of hyoid bone insertion tendinitis.

PMID- 17203311
TI  - Assessment of oral trigeminal sensitivity in humans.
AB  - The aim of this prospective study was to establish a clinical test for the
      assessment of oral trigeminal sensitivity. Capsaicin-impregnated filter paper
      strips (five concentrations: 0.0001-1%) were used to measure trigeminal
      thresholds. The strips were placed on the anterior tongue for 10 s. Subjects were
      asked to report the onset of any sensory perception, quality and duration of
      sensory perception. Thresholds were estimated in two ways: (1) threshold (THR1)
      related to sensory perception and (2) intensity related threshold (THR2). The
      test was applied to 63 healthy subjects (mean age 40 years; 34 women, 29 men).
      For whole-mouth testing with capsaicin, a small but significant correlation was
      found between THR1 and THR2 (r (63) = 0.41). Coefficients of correlation between
      test and re-test were r (30) = 0.60 for THR1 and r (30) = 0.78 THR2. Neither THR1
      nor THR2 indicated either side or sex-related differences. Age-related
      differences were only found in THR2 scores, which were lower in young subjects
      (<40 years). Reliable assessment of intraoral trigeminal sensitivity appears to
      be possible using the presently described technique.

PMID- 17203312
TI  - Surgical treatment of exercise-induced laryngeal dysfunction.
AB  - A method for combined ergo-spirometry and continuous laryngeal inspection during
      exercise, entitled continuous laryngoscopy exercise test (CLE-test) has been
      developed in order to study airway obstruction at the laryngeal level during
      exercise. The aim of the study was to apply the CLE-test on patients experiencing
      respiratory distress during exercise in order to reveal the usefulness of the CLE
      test both as a diagnostic tool in the selection of patients for surgery and in
      evaluation of treatment effects postoperatively. Until now, 81 patients with a
      history of exercise-induced stridor have undergone the CLE-test. Ten of these
      patients were selected for surgical treatment based on the severity of symptoms
      and their motivation for treatment. All ten patients underwent endoscopic
      supraglottoplasty (ES), with laser incision in both aryepiglottic folds anterior
      to the cuneiform cartilages and removal of the mucosa around the top of the
      tubercles. Each patient was examined by the CLE-test before and 3 months after
      surgery. Eight patients felt subjectively that their breathing capacity during
      exercise was improved. When pre- and postoperative ergo-spirometry evaluations
      were compared, increased peak oxygen consumption was observed in four out of ten
      patients and better maximal minute ventilation in seven out of ten. Postoperative
      evaluation of the laryngeal images showed less prominent aryepiglottic folds. The
      typical adduction of the supraglottic structures concomitant with inspiratory
      stridor found preoperatively was not present in any of the patients during
      exercise postoperatively. The ES procedure is an efficient surgical treatment for
      exercise-induced laryngeal supraglottic obstruction and the CLE-test eases the
      selection of patients for surgery and facilitates the evaluation of treatment
      effects.

PMID- 17203313
TI  - Molecular insights into nitrogenase FeMo cofactor insertion: the role of His 362
      of the MoFe protein alpha subunit in FeMo cofactor incorporation.
AB  - The assembly of the complex iron-molybdenum cofactor (FeMoco) of nitrogenase
      molybdenum-iron (MoFe) protein has served as one of the central topics in the
      field of bioinorganic chemistry for decades. Here we examine the role of a MoFe
      protein residue (His alpha362) in FeMoco insertion, the final step of FeMoco
      biosynthesis where FeMoco is incorporated into its binding site in the MoFe
      protein. Our data from combined metal, activity and electron paramagnetic
      resonance analyses show that mutations of His alpha362 to small uncharged Ala or
      negatively charged Asp result in significantly reduced FeMoco accumulation in
      MoFe protein, indicating that His alpha362 plays a key role in the process of
      FeMoco insertion. Given the strategic location of His alpha362 at the entry point
      of the FeMoco insertion funnel, this residue may serve as one of the initial
      docking points for FeMoco insertion through transient ligand coordination and/or
      electrostatic interaction.

PMID- 17203314
TI  - Histidine ligands in bacterial metallothionein enhance cluster stability.
AB  - The cyanobacterial metallothionein (MT) SmtA is the prototype for bacterial MTs
      and protects against elevated levels of zinc. In contrast to mammalian MTs,
      bacterial MTs coordinate to metal ions not only via cysteine sulfurs, but
      unusually for MTs, also via histidine nitrogens. To investigate whether histidine
      coordination in these metal-sulfur clusters provides advantages over S
      coordination only, we mutated the two metal-binding histidine residues in the
      cyanobacterial MT SmtA from Synechococcus PCC7942 to cysteines. We show that the
      mutant proteins are still capable of binding up to four zinc ions as is the wild
      type protein. However, the mutations perturb protein folding and metal-binding
      dynamics. Interestingly, several homologues of SmtA also show variations in these
      two residues. We conclude that histidine residues in Synechococcus PCC7942 SmtA
      have a stabilising effect due to electrostatic interactions that impact on
      protein folding and metal cluster charge, and are involved in fine-tuning the
      reactivity of the bound metal ions.

PMID- 17203315
TI  - Cell traction force and measurement methods.
AB  - Cell traction forces (CTFs) are crucial to many biological processes such as
      inflammation, wound healing, angiogenesis, and metastasis. CTFs are generated by
      actomyosin interactions and actin polymerization and regulated by intracellular
      proteins such as alpha-smooth muscle actin (alpha-SMA) and soluble factors such
      as transforming growth factor-beta (TGF-beta). Once transmitted to the
      extracellular matrix (ECM) through stress fibers via focal adhesions, which are
      assemblies of ECM proteins, transmembrane receptors, and cytoplasmic structural
      and signaling proteins (e.g., integrins), CTFs direct many cellular functions,
      including cell migration, ECM organization, and mechanical signal generation.
      Various methods have been developed over the years to measure CTFs of both
      populations of cells and of single cells. At present, cell traction force
      microscopy (CTFM) is among the most efficient and reliable method for determining
      CTF field of an entire cell spreading on a two-dimensional (2D) substrate
      surface. There are currently three CTFM methods, each of which is unique in both
      how displacement field is extracted from images and how CTFs are subsequently
      estimated. A detailed review and comparison of these methods are presented.
      Future research should improve CTFM methods such that they can automatically
      track dynamic CTFs, thereby providing new insights into cell motility in response
      to altered biological conditions. In addition, research effort should be devoted
      to developing novel experimental and theoretical methods for determining CTFs in
      three-dimensional (3D) matrix, which better reflects physiological conditions
      than 2D substrate used in current CTFM methods.

PMID- 17203316
TI  - A new treatment for back pain?

PMID- 17203317
TI  - Decrease in extracellular collagen crosslinking after NMR magnetic field
      application in skin fibroblasts.
AB  - Although biological effects of electromagnetic fields were investigated
      intensively, there is still no agreement on the significance of their effects.
      The underlying mechanisms and therapeutic importance are still mostly unknown
      too. In this study, primary cultures of human dermal fibroblasts were exposed to
      magnetic field at nuclear magnetic resonance (NMR) conditions for in total 5 days
      and 4 h/day. Among the investigated parameters were: cell proliferation rate,
      cell morphology, total protein concentration as well as content of skin-specific
      collagen types I, III, IV. NMR exposure induced distinct changes both in cellular
      and extracellular components. The extracellular matrix (ECM) of NMR-exposed cells
      had less cross-linked collagen. In particular, the increase of collagen of the
      soluble fraction was at 17.2 +/- 2.9% for type I, 27.0 +/- 1.86% for type III,
      17.3 +/- 1.46% for type IV (N = 6). In the absence of resonance frequency, the
      effects of magnetic field on ECM were less profound.

PMID- 17203318
TI  - Dealing with mismatched fMRI activations in fMRI constrained EEG cortical source
      imaging: a simulation study assuming various mismatch types.
AB  - Although fMRI constrained EEG source imaging could be a promising approach to
      enhancing both spatial and temporal resolutions of independent fMRI and EEG
      analyses, it has been frequently reported that a hard fMRI constraint may cause
      severe distortion or elimination of significant EEG sources when there are
      distinct mismatches between fMRI activations and EEG sources. If estimating
      actual EEG source locations is important and fMRI prior information is used as an
      auxiliary tool to enhance the concentration of widespread EEG source
      distributions, it is reasonable to weaken the fMRI constraint when significantly
      mismatched sources exist. The present study demonstrates that the mismatch
      problem may be partially solved by extending the prior fMRI activation regions
      based on the conventional source imaging results. A hard fMRI constraint is then
      applied when there is no distinct mismatch, while a weakened fMRI constraint is
      applied when there are significant mismatches. A preliminary simulation study
      assuming different types of mismatches such as fMRI invisible, extra, and
      discrepancy sources demonstrated that this approach can be a promising option to
      treat mismatched fMRI activations in fMRI constrained EEG source imaging.

PMID- 17203320
TI  - Relation between branching patterns and perfusion in stochastic generated
      coronary arterial trees.
AB  - Biological variation in branching patterns is likely to affect perfusion of
      tissue. To assess the fundamental consequences of branching characteristics, 50
      stochastic asymmetrical coronary trees and one non-stochastic symmetrical
      branching tree were generated. In the stochastic trees, area growth, A, at
      branching points was varied: A = random; 1.00; 1.10; 1.13 and 1.15 and symmetry,
      S, was varied: S = random; 1.00; 0.70; 0.58; 0.50 and 0.48. With random S and A
      values, a large variation in flow and volume was found, linearly related to the
      number of vessels in the trees. Large A values resulted in high number of vessels
      and high flow and volume values, indicating vessels connected in parallel.
      Lowering symmetry values increased the number of vessels, however, without
      changing flow, indicating a dominant connection of vessels in series. Both large
      A and small S values gave more realistic gradual pressure drops compared to the
      symmetrical non-stochastic branching tree. This study showed large variations in
      tree realizations, which may reflect real biological variations in tree
      anatomies. Furthermore, perfusion of tissue clearly depends on the branching
      rules applied.

PMID- 17203319
TI  - Snakes based segmentation of the common carotid artery intima media.
AB  - Ultrasound measurements of the human carotid artery walls are conventionally
      obtained by manually tracing interfaces between tissue layers. In this study we
      present a snakes segmentation technique for detecting the intima-media layer of
      the far wall of the common carotid artery (CCA) in longitudinal ultrasound
      images, by applying snakes, after normalization, speckle reduction, and
      normalization and speckle reduction. The proposed technique utilizes an improved
      snake initialization method, and an improved validation of the segmentation
      method. We have tested and clinically validated the segmentation technique on 100
      longitudinal ultrasound images of the carotid artery based on manual measurements
      by two vascular experts, and a set of different evaluation criteria based on
      statistical measures and univariate statistical analysis. The results showed that
      there was no significant difference between all the snakes segmentation
      measurements and the manual measurements. For the normalized despeckled images,
      better snakes segmentation results with an intra-observer error of 0.08, a
      coefficient of variation of 12.5%, best Bland-Altman plot with smaller
      differences between experts (0.01, 0.09 for Expert1 and Expert 2, respectively),
      and a Hausdorff distance of 5.2, were obtained. Therefore, the pre-processing of
      ultrasound images of the carotid artery with normalization and speckle reduction,
      followed by the snakes segmentation algorithm can be used successfully in the
      measurement of IMT complementing the manual measurements. The present results are
      an expansion of data published earlier as an extended abstract in IFMBE
      Proceedings (Loizou et al. IEEE Int X Mediterr Conf Medicon Med Biol Eng POS-03
      499:1-4, 2004).

PMID- 17203321
TI  - Embryological development of pacemaker hierarchy and membrane currents related to
      the function of the adult sinus node: implications for autonomic modulation of
      biopacemakers.
AB  - The sinus node is an inhomogeneous structure. In the embryonic heart all myocytes
      have sinus node type pacemaker channels (I (f)) in their sarcolemma. Shortly
      before birth, these channels disappear from the ventricular myocytes. The
      response of the adult sinus node to changes in the interstitium, in particular to
      (neuro)transmitters, results from the interplay between the responses of all of
      its constituent cells. The response of the whole sinus node cannot be simply
      deduced from these cellular responses, because all cells have different responses
      to specific agonists. A biological pacemaker will be more homogeneous. Therefore
      it can be anticipated that tuning of cycle length may be problematic. It is
      discussed that efforts to create a biological pacemaker responsive to vagal
      stimulation, may be counterproductive, because it may have the potential risk of
      'standstill' of the biological pacemaker. A normal sinus node remains
      spontaneously active at high concentrations of acetylcholine, because it has
      areas that are unresponsive to acetylcholine. The same is pertinent to other
      substances with a negative chronotropic effect. Such functional inhomogeneity is
      lacking in biological pacemakers.

PMID- 17203323
TI  - An unusual case of pancytopenia associated with Sheehan's syndrome.

PMID- 17203324
TI  - The effect of leptin on intestinal recovery following ischemia-reperfusion injury
      in a rat.
AB  - Recent evidence suggests that the adipose tissue derived cytokine leptin (LEP) is
      involved in the modulation of growth and differentiation of normal small
      intestine. The purpose of the present study was to examine the effect of leptin
      on enterocyte turnover and intestinal recovery after ischemia-reperfusion (IR)
      injury in a rat. Male Sprague-Dawley rats were divided into three experimental
      groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of
      both superior mesenteric artery and portal vein for 30 min followed by 24 h of
      reperfusion, and (3) IR-LEP rats underwent IR and were treated with leptin given
      subcutaneously at a dose of 50 microg/kg once a day for 48 h before and 24 h
      following IR. Intestinal structural changes, enterocyte proliferation and
      enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal
      Wallis ANOVA test was used for statistical analysis with P < 0.05 considered
      statistically significant. Treatment with leptin resulted in a significant
      increase in bowel weight in ileum, mucosal weight in jejunum and ileum, mucosal
      DNA content in ileum, mucosal protein content in jejunum and ileum, villus height
      in jejunum and ileum, and crypt depth in jejunum compared to IR-animals. IR-LEP
      rats also had a significantly lower intestinal injury score as well as lower
      apoptotic index and higher cell proliferation index in jejunum and ileum compared
      to the IR-animals. In conclusion, pre-treatment with leptin prevents gut mucosal
      damage and improves intestinal rehabilitation following intestinal IR in a rat.

PMID- 17203322
TI  - [Molecular and parametric imaging with iron oxides].
AB  - Superparamagnetic iron oxide (SPIO) contrast agents, clinically established for
      high resolution magnetic resonance imaging of reticuloendothelial system
      containing anatomical structures, can additionally be exploited for the non
      invasive characterization and quantification of pathology down to the molecular
      level. In this context, SPIOs can be applied for non-invasive cell tracking,
      quantification of tissue perfusion and target specific imaging, as well as for
      the detection of gene expression. This article provides an overview of new
      applications for clinically approved iron oxides as well of new, modified SPIO
      contrast agents for parametric and molecular imaging.

PMID- 17203326
TI  - Observations at the craniocervical junction with simultaneous caudal traction of
      the spinal cord.
AB  - INTRODUCTION: Some have opined that caudal traction of the spinal cord may result
      in caudal descent of the hindbrain. MATERIALS AND METHODS: In fresh adult
      cadavers (n = 12; less than 6 h postmortem) with no CIM, distal tension (75 N)
      was applied to the conus medullaris with simultaneous observation of the cervical
      spinal cord, brainstem, and hindbrain and their relationship to the foramen
      magnum per occipital craniectomy and removal of the posterior arch of C1.
      RESULTS: After lumbar laminectomy in cadavers, caudal tension on the cord (conus
      medullaris) demonstrated negligible movement (less than 1 mm) of the caudal brain
      stem and cervical spinal cord. No movement of the cerebellar tonsils was
      identified. Moreover, after transection of the lumbar dural cul-de-sac and lumbar
      spinal dural nerve sleeves, distal traction produced only 2 to 3 mm of caudal
      descent of the brain stem and cervical spinal cord. Again, no movement of the
      cerebellar tonsils was visualized. CONCLUSIONS: Our findings in a fresh cadaveric
      model suggest that it is unlikely that caudal fixation of the distal spinal cord
      results in inferior displacement of the cerebellar tonsils, and a resultant
      Chiari I malformation or that transection of the filum terminale may reverse
      tonsillar ectopia. In vivo animal studies are now necessary to verify our
      findings.

PMID- 17203325
TI  - Altered regulation of retinoic acid synthesis in nitrofen-induced hypoplastic
      lung.
AB  - Retinoids are a group of molecules derived from vitamin A, which play an
      important role in lung development. Within the cell, retinol can either be
      oxidized to retinal or esterified to retinyl esters by lecithin : retinol
      acyltransferase (LRAT) for storage. Retinal is then oxidized to an active
      metabolite of vitamin A, retinoic acid (RA) by retinal dehydrogenase (RALDH). RA
      is the active metabolite of vitamin A. Cyp26 (a1,b1, and c1), which is a member
      of the cytochrome P450 family, acts by reducing the activity of RA. Cyp26 type b1
      is the predominant subtype expressed in the murine lung. Several studies have
      suggested that nitrofen may interfere with the retinoid pathway resulting in
      congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia. Recently, it was
      reported that nitrofen may act by inhibiting RALDH2. The aim of this study was to
      examine the pulmonary expression of Cyp26b1, LRAT, and RALDH2, the key enzymes
      involved in the synthesis of RA, in order to understand the mechanisms underlying
      pulmonary hypoplasia in the nitrofen CDH model. Pregnant rats were exposed to
      either olive oil or 100 mg of nitrofen on day 9 of gestation (D9). Fetal lungs
      were harvested at D15, D17, D19, and D21. D17, D19, and D21 lungs were divided
      into three groups: control, nitrofen without CDH and nitrofen with CDH, whereas
      D15 lungs were divided into only two groups; control and nitrofen as the
      diaphragm is not fully formed yet at this stage. Real- time PCR was performed to
      evaluate the relative level of Cyp26b1, LRAT, and RALDH2 expression in the lung.
      Relative levels of Cyp26b1 mRNA were significantly decreased in the lungs of
      nitrofen with CDH (D17;0.19 +/- 0.09, D19;0.70 +/- 0.20, D21;0.40 +/- 0.36) and
      nitrofen without CDH (D17;0.14 +/- 0.06, D19;0.54 +/- 0.42, D21;0.51 +/- 0.56)
      compared to controls (D17;0.35 +/- 0.16, D19;1.15 +/- 0.48, D21;1.28 +/- 0.78) (P
      < 0.05). LRAT expression was also significantly decreased in nitrofen with CDH
      (D17; 19.3 +/- 7.8, D19; 4.3 +/- 1.1, D21; 3.3 +/- 1.6) and nitrofen without CDH
      (D17; 21.2 +/- 11.1, D19; 4.5 +/- 3.6, D21; 4.1 +/- 1.6) compared to controls
      (D17; 153.7 +/- 29.8, D19; 26.8 +/- 16.8 D21; 10.1 +/- 3.8) (P < 0.05). There was
      no significant difference in the relative levels of Cyp26b1 and LRAT between
      nitrofen with CDH and nitrofen without CDH. There were no significant differences
      in RALDH2 expression among the groups at any stages. Down-regulation of Cryp26b1
      and LRAT demonstrates that RA content is decreased in nitrofen induced
      hypoplastic lungs compared to controls. The finding that RALDH2 expression in the
      hypoplastic lung is not altered suggests that nitrofen may act by interfering
      with the retinoid metabolism during the early stage of the retinoid signaling
      pathway.

PMID- 17203327
TI  - Vaginal reconstruction with sigmoid colon in vaginal agenesis.
AB  - This study was conducted to evaluate the anatomical and functional results of
      sigmoid colon vaginoplasty. From June 2000 to June 2005, 26 patients with
      congenital vaginal agenesis were evaluated and treated with sigmoid colon
      reconstruction at Ain Shams University Maternity Hospital as a primary procedure
      in 17 patients and a secondary procedure in 9 patients after previous failed Abbe
      McIndoe vaginoplasty elsewhere. The anatomical results were good in 22 patients,
      while 3 patients suffered from introital stenosis. Two of them were treated
      successfully by dilatation while one required Z-plasty. Eight patients were lost
      to follow-up and only ten patients are currently sexually active as the rest were
      divorced or remained unmarried. Of the sexually active patients, 8 (80%) had
      satisfactory intercourse whereas 2 (20%) complained of dyspareunia. Sigmoid colon
      vaginoplasty has satisfactory long-term anatomical and functional results and
      should be considered as primary option for the treatment of vaginal agenesis.

PMID- 17203328
TI  - Vesicovaginal fistula resulting from a well-cared-for pessary.
AB  - An 84-year-old vaginally grand multiparous woman presented with a vesicovaginal
      fistula (VVF) after appropriate use of a Gehrung pessary for the past 12 years
      for stage III pelvic organ prolapse. The patient reported strict adherence to
      removing her pessary nightly and replacing it in the morning for the last 12
      years. One morning, she awoke and noted a sudden gush of urine through the vagina
      followed by continuous leakage. Given the complex nature of VVF repair with
      concurrent stage III pelvic organ prolapse, the patient was referred to
      urogynecologic care. A Latzko fistula repair and LeFort colpocleisis were
      performed without complication. The patient recovered well with complete
      resolution of her pelvic organ prolapse and VVF based on negative cystogram
      findings at 3 weeks postoperatively. At 12 weeks postoperatively the patient
      denied any urine leakage or pelvic organ prolapse.

PMID- 17203329
TI  - Association of clinical and pathologic variables with lumpectomy surgical margin
      status after preoperative diagnosis or excisional biopsy of invasive breast
      cancer.
AB  - PURPOSE: To evaluate the impact of preoperative diagnosis in obtaining negative
      lumpectomy margins. MATERIALS AND METHODS: Five hundred and thirty five patients
      who underwent breast conserving therapy for stage I/II cancer from 1971 to 1996
      were included in this IRB-approved retrospective analysis. Three hundred and
      ninety five patients had a defined inked margin status after initial excision.
      The following factors were evaluated for correlation with margins at initial
      excision: age (< or >45), grade (3/1 or 2), family history (present/absent),
      histology (lobular/other), estrogen receptor (ER) status, presence of extensive
      intraductal carcinoma (EIC), presence of lymphovascular invasion (LVI), and
      biopsy type (excisional/preoperative). RESULTS: Biopsy type (P < 0.0001), EIC (P
      = 0.002), ER status (P = 0.02), lobular histology (P = 0.02) and age (P = 0.02)
      were significantly correlated with initial margin status among the entire group.
      For patients who underwent preoperative diagnostic biopsy, 52% (35/67) had
      negative initial margins as compared to 29% (94/328) for excisional biopsy. Among
      patients who underwent preoperative biopsy, only lobular histology (P = 0.04) and
      LVI (P = 0.04) were related to initial margin status. The rate of re-excision was
      34% for patients diagnosed preoperatively versus 61% with excisional biopsy (P <
      0.0001). The percentage of patients with negative final margin status was similar
      with either core/needle or excisional biopsy (79 and 78%, respectively).
      CONCLUSIONS: Preoperative diagnosis is the most significant predictor of initial
      margin status in patients undergoing breast conservation. Patients with lobular
      histology may require improved preoperative and/or intraoperative assessment to
      increase the rate of negative margins at initial excision.

PMID- 17203330
TI  - Sclerosing hepatic carcinoma: helical CT features.
AB  - BACKGROUND: The purpose of this study was to describe our experience,
      particularly for CT features, with four patients who had pathologically proven
      sclerosing hepatic carcinoma that mimicked other malignant hepatic tumors with
      abundant fibrosis at CT. METHODS: Over a 10-year period, we collected four
      patients with surgically proven sclerosing hepatic carcinoma. All patients were
      men (age range, 49-63 years; mean, 56 years). Three-phase helical CT images were
      obtained in all patients, and their CT features were correlated with pathologic
      findings. RESULTS: The tumor size ranged from 2.7 to 11 cm (mean, 7.2 cm). The
      tumors were manifested as a hypoattenuating mass with peripheral, rim enhancement
      at hepatic arterial phase, followed by centripetal enhancement progressively
      during portal venous and equilibrium phases. Histopathologically, the tumors
      showed features intermediate between hepatocellular carcinoma and
      cholangiocarcinoma with abundant fibrosis and surrounding liver had no liver
      cirrhosis. CONCLUSION: As described above, the CT features of sclerosing hepatic
      carcinoma may be similar to other malignant hepatic tumors with abundant
      fibrosis. Although sclerosing hepatic carcinoma is extremely rare, the
      radiologists should recognize that this tumor may be one of the malignant hepatic
      tumors with abundant fibrosis, especially in the non-cirrhotic liver.

PMID- 17203332
TI  - The impact of rheologically controlled materials on the identification of airway
      compromise on the clinical and videofluoroscopic swallowing examinations.
AB  - Numerous studies have suggested that the clinical evaluation of swallowing fails
      to adequately identify those patients who aspirate or do not aspirate on a
      videofluoroscopic swallowing examination. These conclusions, however, are based
      on comparisons between swallowed materials that were not rheologically matched.
      The present study used a battery of rheologically matched test materials,
      involving thin and thick liquids and cohesive and adhesive semisolids. Using
      these test items, results from a clinical swallow evaluation were compared to the
      results of a videofluorographic evaluation using identical test materials.
      Results suggest that the use of three test materials, including thin and thick
      liquids given in volumes of 5 and 10 ml, demonstrated the strongest associations
      between cough on the clinical examination and aspiration on the videofluoroscopic
      examination.

PMID- 17203331
TI  - Leakage of fluid in different types of tracheal tubes.
AB  - The aim of this study was to evaluate leakage of liquids, i.e., water and saliva,
      past low-pressure cuffs of tracheostomy tubes. Three different types of
      tracheostomy tubes, TRACOE vario (TRACOE Medical GmbH, Germany), Rusch Ultra
      Tracheoflex (Rusch GmbH, Germany), and Portex Blue Line Ultra (Smiths Medical,
      UK) were tested in isolated pig tracheas. Sixty samples (10 tubes each of 7- and
      8-mm inner diameter of each type) were used. Four different experiments were
      devised: type 1 (water and artificial ventilation), type 2 (water and no
      artificial ventilation), type 3 (saliva and artificial ventilation), and type 4
      (saliva and no artificial ventilation). Six milliliters of water or artificial
      saliva were infused over the cuff and the volume of fluid that leaked past the
      cuff was measured after 5, 10, and 15 min. Intracuff pressure was also measured
      three times. The saliva experiments resulted in less leakage than the water
      experiments. Leakage after treatment with water or artificial saliva is higher
      without artificial ventilation than with ventilation. The amount of leakage among
      the tubes with respect to manufacturer showed statistically significant results.
      However, there were no differences among tracheostomy tubes with respect to
      internal diameter.

PMID- 17203333
TI  - Oral and oropharyngeal perceptions of fluid viscosity across the age span.
AB  - Research demonstrates that varying sensory input, including the characteristics
      of a bolus, changes swallow physiology. Altering the consistency of fluids is a
      common compensatory technique used in dysphagia management to facilitate change.
      However, it is not known what variations in viscosity can be perceived in the
      oral cavity or oropharynx or if age affects oral and oropharyngeal perceptions of
      fluid viscosity. This study aims to establish the ability of normal adults to
      perceive fluid viscosity in the oral cavity and oropharynx and to determine if,
      within this population, there are age-related changes in oral and oropharyngeal
      perceptions. Sensitivity was established by deriving the exponent for the
      psychophysical law for fluid viscosity in both the oral cavity and the
      oropharynx, using modulus-free magnitude estimation with Newtonian fluids of corn
      syrup and water. Sixty normal volunteers, aged 21-84 years, participated. Results
      indicate that the exponent for oral perception of fluid viscosity was 0.3298,
      while for oropharyngeal perception it was 0.3148. Viscosity perception
      deteriorates with increasing age. Men exhibited a more marked deterioration in
      sensitivity than women. This study contributes to the literature on oral and
      oropharyngeal perceptions and on aging. The results provide a basis for work with
      individuals with dysphagia.

PMID- 17203334
TI  - Extraction of metastatic lymph nodes from MR images using two deformable model
      based approaches.
AB  - We presented and evaluated two deformable model-based approaches, region plus
      contour deformation (RPCD), and level sets to extract metastatic cervical nodal
      lesions from pretreatment T2-weighted magnetic resonance images. The RPCD method
      first uses a region deformation to achieve a rough boundary of the target node
      from a manually drawn initial contour, based on signal statistics. After that, an
      active contour deformation is employed to drive the rough boundary to the real
      node-normal tissue interface. Differently, the level sets move a manually drawn
      initial contour toward the desired nodal boundary under the control of the
      evolvement speed function, which is influenced by image gradient force. The two
      methods were tested by extracting 33 metastatic cervical nodes from 18
      nasopharyngeal carcinoma patients. Experiments on a basis of pixel matching to
      reference standard showed that RPCD and level sets achieved averaged percentage
      matching at 82-84% and 87-88%, respectively. In addition, both methods had
      significantly lower interoperator variances than the manual tracing method. It
      was suggested these two methods could be useful tools for the evaluation of
      metastatic nodal volume as an indicator of classification and treatment response,
      or be alternatives for the delineation of metastatic nodal lesions in radiation
      treatment planning.

PMID- 17203335
TI  - Construction of plasmid vector for expression of bacteriocin N15-encoding gene
      and effect of engineered bacteria on Enterococcus faecalis.
AB  - A 6.09-kb plasmids vector pOri253 was constructed from the plasmid pIL253 (5.2
      kb) and a 0.89-kb fragment of oriColE1 from pBluescript II KS. The bifunctional
      plasmid pOri253 conferred erythromycin resistance in both Escherichia coli and
      Enterococcus faecalis. It has unique sites for EcoRI, BamHI, SalI, and PstI
      derived from pIL253 and was lost at a low rate in E. faecalis JCM8726 when
      cultured in Man, Rogosa, & Sharpe broth without antibiotic. The lactococcal
      promoter P23 was inserted at one end of the pOri253 multicloning site. Gene
      expression was assessed by an entAI gene, which produced bacteriocin N15. The E.
      faecalis harboring constructed plasmid carrying P23 (pOrient23) had more
      antibacterial activity than parental E. faecalis JCM8726 and its clone harboring
      non-P23-containing plasmid (pOrient), as determined by means of an overlay
      method.

PMID- 17203336
TI  - Usefulness of indomethacin for patent ductus arteriosus in full-term infants.
AB  - The aim of this retrospective study was to evaluate the effectiveness of
      indomethacin therapy for patent ductus arteriosus (PDA) in full-term infants. The
      patients were 41 full-term infants with a PDA birth weight (BW) > or =2500 g and
      a gestational age (GA) > or =37 weeks. The echocardiographic evaluation and
      medical management of PDA in these infants was similar to that for PDA in low
      birth-weight infants. Indomethacin (0.2-0.25 mg/kg/dose) was given intravenously
      at 12-24-hour intervals within 23 days of birth. Of the 41 infants, 12 showed
      complete closure, and 13 showed improvement of clinical symptoms. These 25
      infants were classified as the responder group (61%). The other 16 infants, who
      did not show improvement in clinical symptoms, were classified as the
      nonresponder group. Statistical analysis revealed no difference between the two
      groups regarding GA, BW, Apgar score at 1 minute, minimum diameter of the DA
      before treatment, the average age at the initiation of treatment, and DA flow
      pattern. No severe adverse reactions were observed in any infant. Indomethacin
      therapy appears to be an effective medical treatment option for PDA in full-term
      symptomatic infants prior to considering surgical treatment.

PMID- 17203337
TI  - Cerebral near infrared spectroscopy is a reliable marker of systemic perfusion in
      awake single ventricle children.
AB  - Clinical assessment of systemic perfusion in single ventricle patients with
      parallel circulation can be difficult in the outpatient setting. Near infrared
      spectroscopy (NIRS) is a noninvasive measure of cerebral oximetry. We measured
      vital signs, pulse oximetry, and NIRS in 20 single ventricle patients with
      parallel circulation prior to routine cardiac catheterization. These variables
      were evaluated to determine the best noninvasive predictor of the superior vena
      cava saturation (SVC(sat)) as a marker for the adequacy of systemic oxygen
      delivery. The mean age was 6.7 months [standard deviation (SD), 8.6] and mean
      weight was 6.5 kg (SD, 2.2). Diagnoses were hypoplastic left heart syndrome (8),
      tricuspid or pulmonary atresia (10), and double-outlet right ventricle variants
      (2), all prior to cavo pulmonary anastomoses or complete repairs. Stepwise
      multiple regression analysis generated a model in which only NIRS was a
      significant independent predictor of SVC(sat) (p = 0.009). These results support
      the conclusion that NIRS can be a useful tool to evaluate awake single ventricle
      patients in the outpatient setting.

PMID- 17203338
TI  - Vasospastic angina in a 13-year-old female patient whose only symptom was
      toothache.
AB  - Vasospastic angina was confirmed in a 13-year-old female patient at autopsy. The
      patient's only symptom was recurrent toothache, which began when she was 10 years
      old. In November 2000, she was evaluated at our medical center; however, all
      examinations were judged normal. Six months later, she suffered a severe
      toothache. She went to school the next morning after the symptoms improved. She
      lost consciousness at school and was given cardiopulmonary resuscitation but
      could not be revived. At autopsy, her three coronary vessels showed marked
      intimal hyperplasia, and multiple focal myocardial infarctions were observed in
      the lateral wall of the left ventricle. The patient's only clinical symptom was
      toothache and none of the physicians realized that this was caused by angina.
      Vasospastic angina begins at a young age and is one of the causes of sudden death
      in adolescents.

PMID- 17203339
TI  - The effects of long-term grazing exclosures on range plants in the Central
      Anatolian Region of Turkey.
AB  - Over the last fifty years, almost half of the steppe rangeland in the Central
      Anatolian Region of Turkey (CAR) has been converted to cropland without an
      equivalent reduction in grazing animals. This shift has led to heavy grazing
      pressure on rangeland vegetation. A study was initiated in June 2003 using 6
      multiscale Modified-Whittaker plots to determine differences in plant composition
      between areas that have not been grazed in 27 years with neighboring grazed plant
      communities. A total of 113 plant species were identified in the study area with
      the ungrazed plots containing 32 plants more than the grazed plots. The major
      species were Astragalus acicularis, Bromus tomentellus, Festuca valesiaca,
      Genista albida, Globularia orientalis, Poa bulbosa, and Thymus spyleus ssp
      rosulans. Grazing impacts on forbs were more pronounced than for grasses and
      shrubs. Based on Jaccard's index, there was only a 37% similarity of plant
      species between the two treatments. Our study led to four generalizations about
      the current grazing regime and long-term exclosures in the steppe rangeland
      around the study area: (1) exclosures will increase species richness, (2) heavy
      grazing may have removed some plant species, (3) complete protection from grazing
      for a prolonged period of time after a long history of grazing disturbance may
      not lead to an increase in desirable plant species with a concomitant improvement
      in range condition, and (4) research needs to be conducted to determine how these
      rangelands can be improved.

PMID- 17203340
TI  - Defining acceptable levels for ecological indicators: an approach for considering
      social values.
AB  - Ecological indicators can facilitate an adaptive management approach, but only if
      acceptable levels for those indicators have been defined so that the data
      collected can be interpreted. Because acceptable levels are an expression of the
      desired state of the ecosystem, the process of establishing acceptable levels
      should incorporate not just ecological understanding but also societal values.
      The goal of this research was to explore an approach for defining acceptable
      levels of ecological indicators that explicitly considers social perspectives and
      values. We used a set of eight indicators that were related to issues of concern
      in the Lake Champlain Basin. Our approach was based on normative theory. Using a
      stakeholder survey, we measured respondent normative evaluations of varying
      levels of our indicators. Aggregated social norm curves were used to determine
      the level at which indicator values shifted from acceptable to unacceptable
      conditions. For seven of the eight indicators, clear preferences were
      interpretable from these norm curves. For example, closures of public beaches
      because of bacterial contamination and days of intense algae bloom went from
      acceptable to unacceptable at 7-10 days in a summer season. Survey respondents
      also indicated that the number of fish caught from Lake Champlain that could be
      safely consumed each month was unacceptably low and the number of streams
      draining into the lake that were impaired by storm water was unacceptably high.
      If indicators that translate ecological conditions into social consequences are
      carefully selected, we believe the normative approach has considerable merit for
      defining acceptable levels of valued ecological system components.

PMID- 17203341
TI  - Characteristics of urban natural areas influencing winter bird use in southern
      Ontario, Canada.
AB  - Characteristics of urban natural areas and surrounding landscapes were identified
      that best explain winter bird use for 28 urban natural areas in southern Ontario,
      Canada. The research confirms for winter birds the importance of area (size) and
      natural vegetation, rather than managed, horticultural parkland, within urban
      natural areas as well as percent urban land use and natural habitat in
      surrounding landscapes. Alien bird density and percent ground feeding species
      increased with percent surrounding urban land use. Higher percent forest cover
      was associated with higher percentages of forest, bark feeding, small (<20 g) and
      insectivorous species. Natural area size (ha) was related to higher species
      richness, lower evenness and higher percentages of insectivorous, forest
      interior, area-sensitive, upper canopy, bark feeding, and non-resident species.
      Higher number of habitat types within natural areas and percent natural habitat
      in surrounding landscapes were also associated with higher species richness.
      Common, resident bird species dominated small areas (<6.5 ha), while less common
      non-residents increased with area, indicative of a nested distribution. Areas at
      least 6.5 ha and more generally >20 ha start to support some area-sensitive
      species. Areas similar to rural forests had >25% insectivores, >25% forest
      interior species, >25% small species, and <5% alien species. Indicator species
      separated urban natural areas from rural habitats and ordination placed urban
      natural areas along a gradient between urban development and undisturbed, rural
      forests. More attention is needed on issues of winter bird conservation in urban
      landscapes.

PMID- 17203342
TI  - Defining indicators and standards for tourism impacts in protected areas: Cape
      Range National Park, Australia.
AB  - Visitors' perceptions of impacts and acceptable standards for environmental
      conditions can provide essential information for the sustainable management of
      tourist destinations, especially protected areas. To this end, visitor surveys
      were administered during the peak visitor season in Cape Range National Park, on
      the northwest coast of Western Australia and adjacent to the iconic Ningaloo
      Reef. The central focus was visitors' perceptions regarding environmental
      conditions and standards for potential indicators. Conditions considered of
      greatest importance in determining visitors' quality of experience included
      litter, inadequate disposal of human waste, presence of wildlife, levels of
      noise, and access to beach and ocean. Standards were determined, based on
      visitors' perceptions, for a range of site-specific and non-site-specific
      indicators, with standards for facilities (e.g., acceptable number of parking
      bays, signs) and for negative environmental impacts (e.g., levels of littering,
      erosion) sought. The proposed standards varied significantly between sites for
      the facilities indicators; however, there was no significant difference between
      sites for environmental impacts. For the facilities, the standards proposed by
      visitors were closely related to the existing situation, suggesting that they
      were satisfied with the status quo. These results are considered in the context
      of current research interest in the efficacy of visitor-derived standards as a
      basis for protected area management.

PMID- 17203343
TI  - Screening and characterization of a novel fibrinolytic metalloprotease from a
      metagenomic library.
AB  - A metagenomic library was constructed using total genomic DNA extracted from the
      mud in the west coast of Korea and was used together with a fosmid vector,
      pCC1FOS in order to uncover novel gene sources. One clone from approximately
      30,000 recombinant Escherichia coli clones was identified that showed proteolytic
      activity. The gene for the proteolytic enzyme was subcloned into pUC19 and
      sequenced, and a database search for homologies revealed it to be a zinc
      dependent metalloprotease. The cloned gene included the intact coding gene for a
      novel metalloproteinase and its own promoter. It comprised an open reading frame
      of 1,080 base pairs, which encodes a protein of 39,490 Da consisting of 359 amino
      acid residues. A His-Glu-X-X-His sequence, which is a conserved sequence in the
      active site of zinc-dependent metalloproteases, was found in the deduced amino
      acid sequence of the gene, suggesting that the enzyme is a zinc-dependent
      metalloprotease. The purified enzyme showed optimal activity at 50 degrees C for
      1 h and pH 7.0. The enzyme activity was inhibited by metal-chelating reagents,
      such as EDTA, EGTA and 1,10-phenanthroline. The enzyme hydrolyzed azocasein as
      well as fibrin. Thus, the enzyme could be useful as a therapeutic agent to treat
      thrombosis.

PMID- 17203344
TI  - Influence of RGD-containing oligopeptide-coated surface on bone formation in
      vitro and in vivo.
AB  - New bone formation on an RGD-containing oligopeptide-coated surface in vitro and
      in vivo was investigated. The surface showed two-fold higher osteoblastic cell
      adhesion and differentiation in vitro, and revealed statistically significant in
      vivo bone formation compared with the control (P < 0.05).

PMID- 17203345
TI  - Isolation and characterization of thermotolerant bacterium utilizing ammonium and
      nitrate ions under aerobic conditions.
AB  - A thermotolerant bacterium, identified as Bacillus licheniformis, completely
      utilized 0.1% (w/v) NH(4)NO(3) at 30 and 50 degrees C under aerobic condition.
      The addition of 0.5 mM Fe(2+) to the NH(4)NO(3 )medium markedly promoted the
      utilization of NH (4) (+) and NO (3) (-). At 50 degrees C, of total nitrogen
      originally provided, 24% was taken up into the cells and 20% remained in the
      culture supernatant. Residual nitrogen (56%) was probably removed into the
      atmosphere. The cell extracts contained enzymes involved in denitrification. GC
      MS demonstrated that NH (4 ) (15) NO(3) had been converted to (15)N(2)O. These
      results indicate that the strain has denitrification ability under aerobic
      condition.

PMID- 17203346
TI  - An unusual case of transitional cell carcinoma of renal pelvis presenting with
      brain metastases.
AB  - We report a rare case, who had presented with a constellation of neurological
      symptoms (due to multiple brain metastases), but without any urological symptoms,
      to the department of neurosurgery. The patient was managed with gamma knife
      stereotactic radiosurgery for the metastatic lesions. During an evaluation for
      primary, he was found to be having transitional cell carcinoma (TCC) of right
      renal pelvis, for which palliative radical nephroureterectomy was performed,
      following which he received four cycles of paclitaxel and carboplatin
      chemotherapy. The patient is alive with stable disease at 22-months follow-up.

PMID- 17203347
TI  - Correlation between the total volume, transitional zone volume of the prostate,
      transitional prostate zone index and lower urinary tract symptoms (LUTS).
AB  - OBJECTIVES: Currently available studies show controversial data between the
      symptoms of the lower urinary tract and the volume of the prostate gland. The
      objective of the present study is to evaluate the relationship between the score
      of the lower urinary tract symptoms assessed according to the International
      Prostate Symptoms Score (IPSS) and the total (TV) and transitional (TZV) zone
      volume of the prostate and transitional prostate zone index (TZI). MATERIALS AND
      METHODS: From 223 men with a mean age of 59.3 years (varying from 50 to 75), the
      scores of lower urinary tract symptoms, measured by the IPSS and TV and TZV,
      determined by transrectal ultrasonographies, were obtained. Furthermore, the TZI
      was determined in all cases by the TZV to TV rate of the prostate. The
      relationship between TV, TZV, and TZI and the data obtained using the symptoms
      score was statistically determined. RESULTS: The TV of the prostate were 25.5 +/-
      10.3, 25.0 +/- 9.3, and 28.9 +/- 13.5 g in individuals with mild, moderate, and
      severe symptoms, respectively (P = 0.15). Similarly, there was no significant
      difference when the TZV (7.6 +/- 6.3, 7.6 +/- 5.8, and 9.6 +/- 6.8 g,
      respectively; P = 0.22) and the TZI (0.26 +/- 0.1, 0.27 +/- 0.1, and 0.30 +/-
      0.1, respectively; P = 0.33) were compared in the groups of men with mild,
      moderate, and severe symptoms of urinary difficulty. However, the quality of life
      (QoL) scores presented progressively worse values (1.7 +/- 1.3, 3.1 +/- 1.4, and
      4.4 +/- 1.2) as the severity of the lower urinary tract symptoms became worse (P
      < 0.001). The Pearson correlation coefficient between the TV (r = 0.15; P =
      0.02), TZV (r = 0.16; P = 0.02), and the TZI (r = 0.14; P = 0.03) with the
      prostate symptom scores showed low values although they were positive and
      statistically significant. The highest correlation was observed when the QoL
      related to urinary symptoms and symptom scores (r = 0.61; P < 0.001) was
      analyzed. CONCLUSIONS: A low correlation was found between the score lower
      urinary tract symptoms assessed by IPSS and the different volumes of the prostate
      gland (TV, TZV) and prostate TZI, and, on the other hand, an inverse correlation
      between the intensity of urinary symptoms and QoL, supporting the idea of
      multifactorial aspects related to the genesis of urinary symptoms in men.

PMID- 17203348
TI  - Acute, late presentation of colo-continent urinary reservoir fistula.
AB  - Complications associated with continent urinary reservoirs are well recognised.
      Fistulae between the pouch and colon are rare but are documented. This uncommon
      complication is reported in the early post-operative period in patients who have
      previously received pelvic radiotherapy. Colonic fistulae are normally secondary
      to malignancy or diverticular disease. We present the first literature report of
      a late, acutely presenting colo-pouch fistula secondary to neither malignancy nor
      diverticular disease. We highlight the need for medical staff to be aware that
      not all stomas are incontinent and the possible dangers to be aware of when an
      acutely unwell, debilitated patient is unable to convey this fact.

PMID- 17203350
TI  - Laparoscopic management for urachal cyst in a 9-year-old boy.
AB  - We report a boy with urachal cyst managed laparoscopically. A 9-year-old boy was
      referred from another hospital with a history of low abdominal pain. We
      laparoscopically excised the urachal cyst, removing all structures within the
      umbilicovesical fascia, including the urachus and each medial umbilical ligament,
      as well as the associated peritoneum from the umbilicus to the bladder dome.
      Laparoscopic management of urachal disease can be performed safely, with minimal
      postoperative pain, excellent cosmetic results and early ambulation. We advocate
      the use of laparoscopic treatment of urachal anomalies in children.

PMID- 17203349
TI  - Predictors of mortality in elderly patients with acute renal failure in a
      developing country.
AB  - This prospective study was undertaken to systematically analyze the predictors of
      mortality in the elderly in a developing country. All elderly patients with ARF
      hospitalized at this tertiary care centre over 1 year were studied. Various
      predictors analyzed were hospital-acquired ARF, causative factors of ARF,
      preexisting hypertension and diabetes mellitus, severity of renal failure
      (initial and peak serum creatinine, need for dialysis), and complications of ARF:
      infection during the course of illness; serum albumin levels and critical illness
      defined as presence of two or more organ system failures excluding renal failure.
      Of 33,301 patients admitted, 4,255 (12.7%) were elderly. Of these 69 (1.6%) had
      ARF. On analysis of the whole group, both young and elderly, age >60 years had an
      independent predictor of mortality (odds ratio 5.6, P = 0.001). Forty-two of the
      69 (60.9%) elderly ARF patients died. The mortality was significantly increased
      in those elderly with hospital-acquired ARF (79.2%, P = 0.027), those with sepsis
      as a cause of ARF (71.2%, P = 0.004), those who required dialysis (72.5%, P =
      0.022), those developing an infection during the course of ARF (87.9%, P = 0.000)
      and in those with a critical illness (90.0%, P = 0.00). On logistic regression
      analysis of those variables that were significant on univariate analysis, only
      critical illness (odds ratio 9.97) and infection during course (odds ratio 9.72)
      were the independent predictors of mortality. To conclude, ARF complicates only
      1.6% of hospitalized elderly patients but is associated with a high mortality
      rate of 61%. Infection during the course of illness and critical illness were the
      independent predictors of mortality.

PMID- 17203351
TI  - Survivin expression in the ureteral wall of high degree vesicoureteral reflux in
      children.
AB  - INTRODUCTION: Survivin is a member of inhibitor of apoptosis protein family which
      suppresses apoptosis and regulates cell division. Survivin was not found to be
      expressed in normal differentiated tissues. CD95 is a cell surface receptor, and
      it is believed to induce cell death in a variety of cells. The goal of this study
      is to evaluate the survivin and CD95 expression in bladder and uerters of
      children operated for vesicoureteral reflux (VUR). MATERIALS AND METHODS: Sixteen
      paraffine embeded ureteral units of 11 children with vecico ureterl reflux were
      treated immunohistochemicaly with survivin and CD95. At operation the distal
      margins of the ureters were send to histologic exam and a full thickness biopsy
      from the anterior bladder wall including muscle and mucosa were performed. The
      control was taken from a urologically normal 9 days old baby who died from
      myocarditis. The sections were stained with the antibody in the regular method
      and the degree of staining was graded from 0 to 3, by a single uropathologist.
      RESULTS: Immunohistochemistry staining with survivin was positive in all ureters.
      We had 13 high grade (grade 3-5) and 3 low grade (grade 1-2) vesicoureteral
      reflux. The average survivin degree of staining in the low grade reflux was 1.33
      compared to 2.3 (P = 0.019) in the high grade refluxing ureters. The staining of
      the control sample was graded 1. The average degree of staining was 1.2 in the
      bladder wall compared to 2.125 in the ureters. CD95 stained mast cells in ureters
      and bladders. CONCLUSIONS: Possitive staining of survivin was found in both
      ureters and urinary bladders of children that underwent surgical repair of
      vesicoureteral reflux. The degree of survivin staining was significantly higher
      in the high grade refluxing ureters compared to low grade reflux and to the
      bladder wall in the same patients.

PMID- 17203352
TI  - Time of administration of a single dose of oral levofloxacin and its effect in
      infectious complications from transrectal prostate biopsy.
AB  - OBJECTIVE: To evaluate the efficacy of two prophylactic schemes for prostate
      biopsy using a single dose of oral levofloxacin given either before, or
      immediately after transrectal ultrasound-guided prostate biopsy. MATERIALS AND
      METHODS: A total of 300 men formed two groups of 150 patients each: the first
      group received one dose of 500 mg of levofloxacin 30 min to an hour before, and
      the second group the same antibiotic immediately after prostate biopsy. No pre
      biopsy enema was used. Side effects after prostate biopsy were recorded, and the
      two groups were compared. RESULTS: Only one patient from the first group
      developed a urinary tract infection after biopsy. A mean number of more than 10
      cores per patient were taken. Haematuria was the most common complaint, followed
      by haemospermia. Haematuria and rectal bleeding were more common in patients
      where more than 8 cores were taken from the prostate (P = 0.005 and P = 0.017,
      respectively). Prostate cancer was detected in 34.3% of patients in total.
      CONCLUSION: The use of a single dose of 500 mg levofloxacin given immediately
      after prostate biopsy proved to be quite effective for the prevention of
      infectious complications, even in the setting of an extensive biopsy protocol.

PMID- 17203353
TI  - A prospective study of the efficacy of Serenoa repens, tamsulosin, and Serenoa
      repens plus tamsulosin treatment for patients with benign prostate hyperplasia.
AB  - INTRODUCTION: Increasing attention has been focused on the use of
      phytotherapeutic agents to alleviate the symptoms of benign prostatic hyperplasia
      (BPH) in recent times. The best described and studied phytotherapeutic agent is
      Serenoa repens (SR). MATERIALS AND METHODS: This prospective study was designed
      to have 3 arms including SR 320 mg per day (N = 20), Tamsulosin (TAM) 0.4 mg per
      day (N = 20) and SR + TAM (N = 20) to reveal the superiority or equivalence
      between these treatment regimens in BPH. RESULTS: The groups were not
      statistically different with regard to increase in maximal urinary flow rate (Q
      (max)) and decrease in International Prostate Symptom Score (I-PSS) (P > 0.05).
      No adverse effect was detected in SR therapy group. CONCLUSION: Treatment of BPH
      by both SR and TAM seems to be effective alone. None of them had superiority to
      another and additionally, combined therapy (SR + TAM) does not provide extra
      benefits. Furthermore SR is a well-tolerated agent that can be used alternatively
      in the treatment of LUTS due to BPH.

PMID- 17203355
TI  - Serum, urinary and stone zinc, iron, magnesium and copper levels in idiopathic
      calcium oxalate stone patients.
AB  - Many theories have been put forward to explain the mechanism of stone formation
      and growth. The aim of this study was to investigate the urinary, serum and stone
      levels of zinc, iron, magnesium, and copper in patients with calcium oxalate
      stones and to investigate urinary and serum element levels in healthy controls
      and to find a possible connection between the elements and calcium oxalate stone
      formation. A total of 104 patients with calcium oxalate stones ranging in age
      from 3 to 79 years (mean 44.0 +/- 18.1) and 77 healthy controls ranging in age
      from 18 to 77 (mean 44.2 +/- 17.9) were included in this study. The mean urinary
      iron and copper levels in stone patients were significantly higher than healthy
      controls (P = 0.000). The mean urinary zinc and magnesium levels in healthy
      controls were significantly higher than stone patients (P = 0.000). There was no
      significant difference in the serum levels of magnesium and copper in stone
      patients and healthy controls. Serum zinc and iron level were significantly high
      in healthy controls as compared to stone patients. Each stone had all 4 elements.
      Zn and Mg have inhibitory effect on calcium oxalate stone formation. Fe and Cu
      could be promotor of the calcium oxalate stone formation.

PMID- 17203354
TI  - Acute liver failure due to leptospirosis successfully treated with MARS
      (molecular adsorbent recirculating system) dialysis.
AB  - BACKGROUND: Leptospirosis is a re-emerging infectious disease, which may lead to
      multiple organ failure (MOF)and death. CASE PRESENTATION: We report the first
      case of severe leptospirosis complicated with acute renal and liver failure,
      successfully treated with albumin dialysis--molecular adsorbent recirculating
      system (MARS). Despite antibiotic therapy, optimum medical supportive treatment
      and timely initiated haemodialysis, the outcome was complicated by severe liver
      failure: hepatic encephalopathy grade III, hypoglycemia, prominent
      hyperbilirubinemia (TBIL 31.3 mg/dl, DBIL 28.6 mg/dl)and hepatic cytolysis (ALT
      535 IU/l, AST 179 IU/l) and prolongation of the prothrombine time (68.4 sec). The
      patient underwent two sesions of albumin dialysis with the MARS procedure with
      complete recovery of hepatic and renal function. CONCLUSION: Albumin dialysis may
      confer a significant survival benefit on patients with leptospirosis-induced
      acute liver failure (ALF).

PMID- 17203356
TI  - Leiomyosarcoma of kidney: a case report with long term result after radiotherapy
      and chemotherapy.
AB  - Leiomyosarcoma of the kidney is a rare entity with poor prognosis. Among renal
      sarcomas, it is the most common histologic subtype amounting to 50-60% of all
      cases. The tumors usually arise from either the renal capsule or smooth muscle
      tissue in the renal pelvic wall. We describe a case of renal leiomyosarcoma that
      presented with history of left flank pain. Physical examination was normal.
      Abdominal ultrasound showed a solid lesion of 38 x 36 mm arising from the left
      kidney. Intravenous urography showed cut off of both major and minor calyces of
      the left kidney from its pelvis with a normal right kidney. Exploratory
      laparotomy revealed a well-encapsulated mass confined to the renal parenchyma for
      which radical nephrectomy was performed. Histopathology showed a Grade I
      leiomyosarcoma arising from the renal capsule. Adjuvant chemotherapy and sandwich
      radiotherapy was given and he is disease free after six and half years of follow
      up. The rarity of this disease, its severity and poor prognosis, uncommon form of
      presentation, resulting delay in diagnosis and difficulty in management is
      highlighted and reported.

PMID- 17203357
TI  - Malignant non-functional paraganglioma of the bladder presenting with azotemia.
AB  - Paragangliomas of the urinary bladder are rare tumors representing less than 1%
      of bladder tumors and are usually benign. Malignant paragangliomas are uncommon
      and are defined by their clinical behavior rather than the histologic features.
      We describe a patient with recurrent nonfunctioning paraganglioma of bladder
      presenting with hematuria and obstructive uropathy due to involvement of
      ureteroileal anastomoses. Treatment consisted of excision of recurrent lesion
      involving both lower ureters with the revision of ureteroileal anastomoses.
      Histology confirmed the presence of nests of tumor cells with abundant
      eosinophilic cytoplasm. Immunohistochemically the tumor cells were strongly
      positive for chromogranin A.

PMID- 17203358
TI  - The spectrum of Vogt-Koyanagi-Harada disease in Tunisia, North Africa.
AB  - OBJECTIVE: To analyze the clinical profile of Vogt-Koyanagi-Harada (VKH) disease
      in Tunisia, North Africa. METHODS: We retrospectively reviewed the clinical
      records of 49 patients diagnosed with VKH disease at the Department of
      Ophthalmology of Fattouma Bourguiba University Hospital, Monastir, Tunisia,
      between January 1994 and September 2005. RESULTS: Of all the uveitis cases
      diagnosed during the study period, VKH disease was the fourth most commonly
      occurring type (7.4%). Thirty-two patients (65.3%) were female, and 17 patients
      (34.7%) were male. The mean age at disease onset was 35 years (range: 16-54
      years). The majority of patients (51%) had probable VKH disease, followed by
      incomplete type (47%); only 2% had the complete type. At presentation, 47
      patients (96%) had bilateral ocular involvement. Clinical presentation was a
      panuveitis in 25 patients (51%) and a posterior uveitis in 24 patients (49%).
      Visual acuity (VA) at presentation ranged from less than 20/200 (40.8%) to more
      than 20/40 (28.5%). All patients were treated with systemic corticosteroids for 2
      19 months (mean: 10.5 months). Four patients (8%) were treated with cyclosporin
      because of serious systemic side effects of corticosteroids. Complications
      included cataract in 18 eyes (33.9%), glaucoma in nine eyes (16.96%) and
      choroidal neovascularization in one eye (1%). Fifty-eight eyes (59%) had a final
      VA of 20/40 or better. Factors associated with a poor VA at the final follow-up
      were the presence of a poor VA at presentation (P = 0.02), the occurrence of
      complications (P = 0.001) and/or recurrences (P = 0.02). CONCLUSION: In Tunisia,
      VKH disease is a common cause of uveitis that predominantly affects young women.
      The overwhelming majority (98%) have probable or incomplete VKH disease,
      presenting as panuveitis or posterior uveitis. More than 50% of patients
      undergoing treatment with corticosteroids will maintain a VA of 20/40 or better.

PMID- 17203359
TI  - Do polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene affect
      the risk of childhood acute lymphoblastic leukemia?
AB  - Meta-analysis has become an important statistical tool in genetic association
      studies, since it may provide more powerful and precise estimates. However, meta
      analytic studies are prone to several potential biases not only because the
      preferential publication of "positive'' studies but also due to difficulties in
      obtaining all relevant information during the study selection process. In this
      letter, we point out major problems in meta-analysis that may lead to biased
      conclusions, illustrating an empirical example of two recent meta-analyses on the
      relation between MTHFR polymorphisms and risk of acute lymphoblastic leukemia
      that, despite the similarity in statistical methods and period of study
      selection, provided partially conflicting results.

PMID- 17203360
TI  - Prediction of complicated urinary tract infections in patients with type 2
      diabetes: a questionnaire study in primary care.
AB  - BACKGROUND: Relatively few data are available to predict a complicated course of
      community-acquired complicated urinary tract infections (UTIs) in patients with
      diabetes type 2 (DM2). The aim of this study was to assess predictors for a
      complicated course of UTIs in DM2 patients in primary care. METHOD: We conducted
      a cross-sectional questionnaire study among DM2 patients aged over 45 years as
      part of an educational trial. The combined outcome measure was a complicated
      course of UTI, defined as a self-reported episode of acute pyelonephritis,
      prostatitis or recurrent cystitis in the 12 months before the trial. Patients
      with an outcome were all verified by review of medical records. A prediction
      model was derived with multivariable logistic regression analysis. RESULTS: Of
      the 1151 trial participants, 94 (8%) had a self-reported community-acquired
      complicated course of UTIs and 62 (66%) of these were medically-attended.
      Independent predictors for a complicated course were age above 60 years (adjusted
      odds ratio (OR): 1.74; 95% confidence interval (CI): 0.99-3.03), chronic use of
      antibiotics (adjusted OR: 5.50; 95% CI: 2.31-13.08), more than 6 physician
      contacts in previous year (adjusted OR: 3.60; 95% CI: 2.00-6.49), hospitalization
      in previous year (adjusted OR: 1.36; 95% CI: 1.00-1.85), renal disease (adjusted
      OR: 4.92; 95% CI: 1.59-15.18) and incontinence of urine (adjusted OR: 3.78; 95%
      CI: 1.93-7.38). Area under the receiver-operating curve was 0.72 (95% CI: 0.66
      0.78). Analysis according to medically attended complicated UTIs did not change
      our findings. CONCLUSION: Easily obtainable predictors from medical history can
      be used to accurately predict a complicated course of UTIs in DM2 patients.

PMID- 17203362
TI  - Shared decision-making, gender and new technologies.
AB  - Much discussion of decision-making processes in medicine has been patient
      centred. It has been assumed that there is, most often, one patient. Less
      attention has been given to shared decision-making processes where two or more
      patients are involved. This article aims to contribute to this special area. What
      conditions need to be met if decision-making can be said to be shared? What is a
      shared decision-making process and what is a shared autonomous decision-making
      process? Why make the distinction? Examples are drawn from the area of new
      reproductive medicine and clinical genetics. Possible gender-differences in
      shared decision-making are discussed.

PMID- 17203361
TI  - Imaging viral infection: studies on Nicotiana benthamiana plants infected with
      the pepper mild mottle tobamovirus.
AB  - We have studied by kinetic Chl-fluorescence imaging (Chl-FI) Nicotiana
      benthamiana plants infected with the Italian strain of the pepper mild mottle
      tobamovirus (PMMoV-I). We have mapped leaf photosynthesis at different points of
      the fluorescence induction curve as well as at different post-infection times.
      Images of different fluorescence parameters were obtained to investigate which
      one could discriminate control from infected leaves in the absence of symptoms.
      The non-photochemical quenching (NPQ) of excess energy in photosystem II (PSII)
      seems to be the most adequate chlorophyll fluorescence parameter to assess the
      effect of tobamoviral infection on the chloroplast. Non-symptomatic mature leaves
      from inoculated plants displayed a very characteristic time-varying NPQ pattern.
      In addition, a correlation between NPQ amplification and virus localization by
      tissue-print was found, suggesting that an increase in the local NPQ values is
      associated with the areas invaded by the pathogen. Changes in chloroplast
      ultrastructure in non-symptomatic leaf areas showing different NPQ levels were
      also investigated. A gradient of ultrastructural modifications was observed among
      the different areas.

PMID- 17203363
TI  - Efficacy of strips coated with Metarhizium anisopliae for control of Varroa
      destructor (Acari: Varroidae) in honey bee colonies in Texas and Florida.
AB  - Strips coated with conidia of Metarhizium anisopliae (Metschinkoff;
      Deuteromycetes: Hyphomycetes) to control the parasitic mite, Varroa destructor
      (Anderson and Trueman) in colonies of honey bees, Apis mellifera (Hymenoptera:
      Apidae) were compared against the miticide, tau-fluvalinate (Apistan) in field
      trials in Texas and Florida (USA). Apistan and the fungal treatments resulted in
      successful control of mite populations in both locations. At the end of the 42
      day period of the experiment in Texas, the number of mites per bee was reduced by
      69-fold in bee hives treated with Apistan and 25-fold in hives treated with the
      fungus; however mite infestations increased by 1.3-fold in the control bee hives.
      Similarly, the number of mites in sealed brood was 13-fold and 3.6-fold higher in
      the control bee hives than in those treated with Apistan and with the fungus,
      respectively. Like the miticide Apistan, the fungal treatments provided a
      significant reduction of mite populations at the end of the experimental period.
      The data from the broodless colonies treated with the fungus indicated that
      optimum mite control could be achieved when no brood is being produced, or when
      brood production is low, such as in the early spring or late fall. In established
      colonies in Florida, honey bee colony development did not increase under either
      Apistan or fungal treatments at the end of the experimental period, suggesting
      that other factors (queen health, food source, food availability) play some major
      role in the growth of bee colonies. Overall, microbial control of Varroa mites
      with fungal pathogens could be a useful component of an integrated pest
      management program for the honey bee industry.

PMID- 17203364
TI  - Strategies to design pyrazolyl urea derivatives for p38 kinase inhibition: a
      molecular modeling study.
AB  - The p38 protein kinase is a serine-threonine mitogen activated protein kinase,
      which plays an important role in inflammation and arthritis. A combined study of
      3D-QSAR and molecular docking has been undertaken to explore the structural
      insights of pyrazolyl urea p38 kinase inhibitors. The 3D-QSAR studies involved
      comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices (CoMSIA). The best CoMFA model was derived from the atom fit alignment
      with a cross-validated r (2 )(q (2)) value of 0.516 and conventional r (2) of
      0.950, while the best CoMSIA model yielded a q (2) of 0.455 and r (2) of 0.979
      (39 molecules in training set, 9 molecules in test set). The CoMFA and CoMSIA
      contour maps generated from these models provided inklings about the influence of
      interactive molecular fields in the space on the activity. GOLD, Sybyl (FlexX)
      and AutoDock docking protocols were exercised to explore the protein-inhibitor
      interactions. The integration of 3D-QSAR and molecular docking has proffered
      essential structural features of pyrazolyl urea inhibitors and also strategies to
      design new potent analogues with enhanced activity.

PMID- 17203365
TI  - 3D-QSAR study of hallucinogenic phenylalkylamines by using CoMFA approach.
AB  - The three-dimensional quantitative structure-activity relationship (3D-QSAR) has
      been studied on 90 hallucinogenic phenylalkylamines by the comparative molecular
      field analysis (CoMFA). Two conformations were compared during the modeling.
      Conformation I referred to the amino group close to ring position 6 and
      conformation II related to the amino group trans to the phenyl ring. Satisfactory
      results were obtained by using both conformations. There were still differences
      between the two models. The model based on conformation I got better statistical
      results than the one about conformation II. And this may suggest that
      conformation I be preponderant when the hallucinogenic phenylalkylamines interact
      with the receptor. To further confirm the predictive capability of the CoMFA
      model, 18 compounds with conformation I were randomly selected as a test set and
      the remaining ones as training set. The best CoMFA model based on the training
      set had a cross-validation coefficient q (2) of 0.549 at five components and non
      cross-validation coefficient R (2) of 0.835, the standard error of estimation was
      0.219. The model showed good predictive ability in the external test with a
      coefficient R (pre) (2) of 0.611. The CoMFA coefficient contour maps suggested
      that both steric and electrostatic interactions play an important role. The
      contributions from the steric and electrostatic fields were 0.450 and 0.550,
      respectively.

PMID- 17203366
TI  - Incorporating partial matches within multi-objective pharmacophore
      identification.
AB  - This paper describes the extension of our earlier multi-objective method for
      generating plausible pharmacophore hypotheses to incorporate partial matches.
      Diverse sets of molecules rarely adopt exactly the same binding mode, and so
      allowing the identification of partial matches allows our program to be applied
      to larger and more diverse datasets. The method explores the conformational space
      of a series of ligands simultaneously with their alignment using a multi
      objective genetic algorithm (MOGA). The principles of Pareto ranking are used to
      evolve a diverse set of pharmacophore hypotheses that are optimised on
      conformational energy of the ligands, the goodness of the overlay and the volume
      of the overlay. A partial match is defined as a pharmacophoric feature that is
      present in at least two, but not all, of the ligands in the set. The number of
      ligands that map to a given pharmacophore point is taken into account when
      evaluating an overlay. The method is applied to a number of test cases extracted
      from the Protein Data Bank (PDB) where the true overlay is known.

PMID- 17203368
TI  - Determination of metal accumulation in deposited street dusts in Amman, Jordan.
AB  - Street dust samples (120 in total) were collected under stable weather conditions
      during the hot, dry season (August and September) of 2004 from six different
      localities (industrial, heavy traffic, medium traffic, light traffic, low traffic
      and rural) in greater Amman, the capital of Jordan. The concentrations of Fe, Cu,
      Cd, Pb, Zn and Ni in the dusts were determined by atomic absorption
      spectrophotometry. The high concentrations of Pb, Fe and Zn in the street dust
      samples were related to both anthropogenic (industrial sources combined with
      traffic sources) and natural sources. Surprisingly, the concentrations of Cd in
      the dusts were low. Correlation coefficient analysis and principle component
      analysis identified three main sources of these elements and the corresponding
      distributions. The elements Pb, Zn, Cd, Fe, Cu and Ni were mainly derived from
      industrial sources, with Pb and Zn additionally derived from traffic sources. The
      street dusts were found to have highly elevated levels of Zn, particularly along
      the main trunk roads, indicating that the Zn in the street dusts may be derived
      from traffic sources, especially vehicle tyres. The concentrations of metals in
      the different street dust samples were found to vary depending on the density of
      traffic.

PMID- 17203367
TI  - Multidisciplinary work on barium contamination of the karstic upper Kupa River
      drainage basin (Croatia and Slovenia); calling for watershed management.
AB  - The present work was designed as an extension of a previous study of a barium
      anomaly observed in stream sediments of the Kupa River. In its upper part the
      Kupa River drains a region underlain by a trans-boundary aquifer. The river is a
      significant water resource in a region of tourism, sport, and fishing in both
      Croatia and Slovenia. The contamination source is situated in Homer (Lokve),
      Croatia, where barite was mined until 10 years ago. The barium processing waste
      material (<3-mm fraction) was carelessly deposited in gardens, forests, and into
      a sinkhole, which has an underground link with the Kupica River, a tributary of
      the Kupa River. Barium waste and stream sediments were analyzed using comparative
      techniques: X-ray diffraction (XRD), X-ray fluorescence (XRF), Mossbauer
      spectroscopy, and grain size analysis. XRD of the waste material identified the
      major minerals quartz, barite, and dolomite and the Fe-containing minor minerals
      muscovite and goethite. Barite was identified as a minor or trace mineral in the
      Kupica River sediments. XRF analysis of the waste material has shown Ba and Fe to
      be the predominant elements, Ca and K to be minor elements, and Mn, Zn, Sr, Pb,
      Co, Cu, As, Zr, Rb, Y, and Mo to be trace elements. Mossbauer spectroscopy
      performed at room temperature (RT) was used to study iron minerals, particularly
      to obtain information on the valence status of Fe ions. Grain size analysis of
      the waste material (<63-microm fraction) has shown that it contains 23.5% clay
      size material in comparison with 7-8% clay-size material in stream sediments. It
      is our aim to combine geochemical and medical methods to investigate the possible
      impact of waste disposal on human health in Lokve. At this stage of the work,
      concentrations of Ba and other toxic elements in the water compartment of the
      Kupica River (a source of drinking water) have not been monitored by Croatian
      Waters (name of the Croatian water authorities). The necessity of such
      measurements in future studies has been highlighted. A preliminary study of
      diseases diagnosed in Lokve shows that about 18% of the total inhabitants have
      serious medical problems. Diseases of the circulatory system, endocrine,
      nutritional, and metabolic diseases, neoplasms, and respiratory diseases
      predominate. This paper calls for further multidisciplinary research on the
      health effects of barium and trace elements, as well as for bioremediation of
      contaminated gardens and for watershed management of vulnerable karstic aquifers.

PMID- 17203370
TI  - Geochemistry of the barkinite liptobiolith (Late Permian) from the Jinshan Mine,
      Anhui Province, China.
AB  - This paper discusses the geochemistry and mineralogy of the barkinite
      liptobiolith of the Late Permian age from the Jinshan Mine, Guangde County, Anhui
      Province, China. Samples were examined using inductively coupled plasma-mass
      spectroscopy, X-ray fluorescence, cold-vapor atomic absorption spectrometry, ion
      selective electrode, sequential chemical extraction, scanning electron microscopy
      equipped with energy-dispersive X-ray, and optical microscopy. The coal is a
      medium-ash and high-sulfur resource. Minerals in the coal are composed of
      kaolinite, pyrite, calcite, and quartz. Pyrite and calcite are derived from
      seawater during peat accumulation. Quartz in the coal is of authigenic origin.
      Part of the kaolinite is from a land-source region, and part occurs as cell
      fillings and is of authigenic origin. The results also indicate that the
      barkinite liptobiolith contains some toxic elements in high concentrations.
      Elements including Li, Be, Si, Sc, Ti, V, Cr, Fe, Ga, Se, Y, Zr, Mo, the rare
      earth elements (REEs), W, Hg, Tl, Pb, Th, and U in the coals are enriched in the
      barkinite liptobiolith. Results of sequential chemical extraction showed that Li,
      Sc, Ti, Cr, Y, Zr, REEs, and Th in the coal mainly occur as silicates, while Be
      and W are related to organic matter. Pyrite is the dominant source of S, Mo, Hg,
      Tl, and Pb. Gallium only occurs in silicate, and U and V occur both in organic
      and silicate associations.

PMID- 17203369
TI  - Distribution and bioaccumulation of organochlorine pesticides along the Black Sea
      coast.
AB  - Sediment, mussel, and seawater samples were collected three times during 2001
      2003 at nine sampling stations along the mid-Black Sea coast of Turkey. The
      samples were analyzed with GC-ECD for contents of various organochlorine
      pesticides (OCPs) in the environment. DDT and its metabolites were detected at
      concentrations significantly above the detection limits. The highest
      concentrations of DDT metabolites measured in the sediment and mussel samples
      were 35.9 and 14.0 ng/g wet weight respectively. Considerable levels of aldrin,
      dieldrin, endrin, heptachlor epoxide, lindane, endosulfan sulphate, and HCB were
      also detected in the sediment, mussel, or seawater samples. Although these
      persistent toxic compounds have been banned for some years in Turkey, they may
      still be used illegally in some regions, contributing to their significant levels
      in the environment. The biota-sediment accumulation factor (BSAF) estimated for
      DDT and its metabolites in mussels was 2.9, which is nearly two times higher than
      the benchmark of 1.7. In spite of such high BSAF values observed for these toxic
      compounds, their levels in mussels were significantly below the international
      legal limits recommended by the Food and Agriculture Organization of the United
      Nations. Edible biota from the waterbodies examined may thus still be considered
      safe for human consumption at this time. However, as pollutants can biomagnify
      through the food chain over time, further routine sampling and analysis of biota
      along the Black Sea coast are warranted in order to better assess the threat of
      OCPs to public health in the region.

PMID- 17203371
TI  - mtDNA diversity and genetic lineages of eighteen cattle breeds from Bos taurus
      and Bos indicus in China.
AB  - In order to clarify the origin and genetic diversity of indigenous cattle breeds
      in China, we carried out phylogenetic analysis of representatives of those breeds
      by employing mitochondrial gene polymorphism. Complete cyt b gene sequences, 1140
      bp in length, were determined for a total of 136 individuals from 18 different
      breeds and these sequences were clustered into two distinct genetic lineages:
      taurine (Bos taurus) and zebu (Bos indicus). In analysis of the cyt b gene
      diversity, Chinese cattle showed higher nucleotide (0.00923) and haplotype
      diversity (0.848) than the reports from other studies, and the animals from the
      taurine lineage indicated higher nucleotide diversity (0.00330) and haplotype
      diversity (0.746) than the ones from the zebu lineage (0.00136; 0.661). The zebu
      mtDNA dominated in the southern breeds (63.3-100%), while the taurine dominated
      in the northern breeds (81.8-100%). Six cattle breeds from the central area of
      China exhibited intermediate frequencies of zebu mtDNA (25-71.4%). This
      polymorphism revealed a declining south-to-north gradient of female zebu
      introgression and a geographical hybrid zone of Bos taurus and Bos indicus in
      China.

PMID- 17203372
TI  - Evaluation of biosorption potency of Acinetobacter sp. for removal of hexavalent
      chromium from tannery effluent.
AB  - Two bacterial consortia were developed by continuous enrichment of microbial
      population of tannery and pulp and paper mill effluent contained Serratia
      mercascens, Pseudomonas fluorescence, Escherichia coli, Pseudomonas aeruginosa
      and Acinetobacter sp. identified by 16S rDNA method. The consortia evaluated for
      removal of chromate [(Cr(VI)] in shake flask culture indicated pulp and paper
      mill consortium had more potential for removal of chromate. Acinetobacter sp.
      isolated from pulp and paper mill consortium removed higher amount of chromate
      [Cr(VI)] under aerobic conditions. Parameters optimized in different carbon,
      nitrogen sources, and pH, indicated maximum removal of chromate in sodium acetate
      (0.2%), sodium nitrate (0.1%) and pH 7 by Acinetobacter sp. Bacteria was applied
      in 2-l bioreactor significantly removed chromate after 3 days. The results of the
      study indicated removal of more than 75% chromium by Acinetobacter sp. determined
      by diphenylcarbazide colorimetric assay and atomic absorption spectrophotometer
      after 7 days. Study of microbial [Cr(VI)] removal and identification of reduction
      intermediates has been hindered by the lack of analytical techniques. Therefore,
      removal of chromium was further substantiated by transmission electron microscopy
      (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray
      spectroscopy (EDX) which indicated bioaccumulation of chromium in the bacterial
      cells.

PMID- 17203374
TI  - Changes in gene expression during male meiosis in Petunia hybrida.
AB  - We analyzed changes in gene expression during male meiosis in Petunia by
      combining the meiotic staging of pollen mother cells from a single anther with
      cDNA-AFLP transcript profiling of mRNA from the synchronously developing sister
      anthers. The transcript profiling experiments focused on the identification of
      genes with a modulated expression profile during meiosis, while premeiotic
      archesporial cells and postmeiotic microspores served as a reference. About 8000
      transcript tags, estimated at 30% of the total transcriptome, were generated, of
      which around 6% exhibited a modulated gene expression pattern at meiosis. Cluster
      analysis revealed a transcriptional cascade that coincides with the initiation
      and progression through all stages of the two meiotic divisions. Fragments that
      exhibited high expression specifically during meiosis I were characterized
      further by sequencing; 90 out of the 293 sequenced fragments showed homology with
      known genes, belonging to a wide range of gene classes, including previously
      characterized meiotic genes. In-situ hybridization experiments were performed to
      determine the spatial expression pattern for five selected transcript tags. Its
      concurrence with cDNA-AFLP transcript profiles indicates that this is an
      excellent approach to study genes involved in specialized processes such as
      meiosis. Our data set provides the potential to unravel unique meiotic genes that
      are as yet elusive to reverse genetics approaches.

PMID- 17203373
TI  - Ectopic expression of a conifer Abscisic Acid Insensitive3 transcription factor
      induces high-level synthesis of recombinant human alpha-L-iduronidase in
      transgenic tobacco leaves.
AB  - We are examining various plant-based systems to produce enzymes for the treatment
      of human lysosomal storage disorders. Constitutive expression of the gene
      encoding the human lysosomal enzyme, alpha-L-iduronidase (IDUA; EC 3.2.1.76) in
      leaves of transgenic tobacco plants resulted in low-enzyme activity, and the
      protein appeared to be subject to proteolysis. Toward enhancing production of
      this recombinant enzyme in vegetative tissues, transgenic tobacco plants were
      generated to co-express a CaMV35S:Chamaecyparis nootkatensis Abscisic Acid
      Insensitive3 (CnABI3) gene construct, along with the human gene construct. The
      latter contained regulatory sequences of the Phaseolus vulgaris arcelin 5-I gene
      (5'-flanking, signal-peptide-encoding, and 3'-flanking regions). Ectopic
      synthesis of the CnABI3 protein led to the transactivation of the arcelin
      promoter and accordingly high activity (e.g., 25,000 pmol/min/mg total soluble
      protein) and levels of recombinant IDUA mRNA and protein were induced in leaves
      of transgenic tobacco, particularly in the presence of 150-200 microM S-(+)-ABA.
      Synthesis of human IDUA containing a carboxy-terminal ER retention (SEKDEL)
      sequence was also inducible by ABA in leaves co-transformed with the CnABI3 gene.
      As compared to the natural S-(+)-ABA, two persistent ABA analogues, (+)-8'
      acetylene ABA and (+)-8'methylene ABA, led to greater levels of beta
      glucuronidase (GUS) reporter activities in leaves co-expressing the CnABI3 gene
      and a vicilin:GUS chimeric gene. In contrast, (+)-8' acetylene ABA and natural
      ABA appeared to be equally effective in stimulating the CnABI3-induced expression
      of an arcelin:GUS gene, and of the human IDUA gene, the latter also driven by
      arcelin-gene-regulatory sequences. Various stress-related treatments,
      particularly high concentrations of NaCl, had an even greater effect than ABA in
      promoting accumulation of human IDUA in co-transformed tobacco leaves. This
      strategy provides the means of enhancing the yields of recombinant proteins in
      transgenic plant vegetative tissues and potentially in cultured plant cells. The
      human recombinant protein can be readily induced in the presence of chemicals
      such as NaCl that can be added to cell cultures or even whole plants without a
      significant increase in production costs.

PMID- 17203378
TI  - Two new species of taeniacanthid copepods (Poecilostomatoida) parasitic on marine
      fishes of Taiwan.
AB  - Two new species of copepods (Poecilostomatoida Taeniacanthidae) parasitic on
      fishes of Taiwan are reported. They are: Irodes parupenei n. sp. from Parupeneus
      spilurus (Bleeker) and P. multifasciatus (Quoy & Gaimard), and Taeniacanthus
      spiniferus n. sp. from Acanthocepola limbata Valenciennes. I. parupenei is
      characteristic in having nine (instead of eight) elements on the terminal segment
      of leg 2 exopod, a spiniform element (instead of a long, plumose seta) on the
      medial margin of the proximal segment of leg 4 endopod, and thee spines and one
      long, naked seta (rather than four short setae) on the slender (rather than
      spatula-like), terminal segment of leg 5. T. spiniferus is distinguished from its
      38 congeners in carrying a pair of sharp tines in the ventral area of the
      rostrum.

PMID- 17203376
TI  - Lamins A and C are present in the nuclei of early porcine embryos, with lamin A
      being distributed in large intranuclear foci.
AB  - Gametogenesis and embryogenesis are dynamic developmental stages marked by
      extensive modifications in the organization of the genome and nuclear
      architecture. In the literature it is conveyed that only B-type lamins are
      required in these early stages of development and that A-type lamins are not
      present or required until differentiation of specific cell types associated with
      specialized tissue is initiated. To assess the presence of nuclear structures
      that are putatively involved in genome regulation, we investigated the
      distribution of lamin proteins throughout the early stages of porcine embryonic
      development, using testes tissue sections, oocytes and in-vitro fertilized (IVF)
      porcine embryos and employing anti-lamin antibodies. We have shown that anti
      lamin A staining is present at the one-cell, two-cell, four-cell, and six- to
      eight-cell stages of early porcine embryo development, but diminishes at the
      morulae and blastocyst stages. Large intranuclear anti-lamin A foci are prominent
      in the early preimplantation stages. Both anti-lamin A/C and anti-lamin B
      staining were clearly present in all embryonic stages. Immature porcine oocytes
      revealed lamin rings using the monoclonal anti-lamin A/C antibody and many
      immature oocytes exhibited a pale rim staining pattern with anti-lamin A
      antibody. A-type lamins were not observed in sperm precursor cells. Thus, we have
      shown that A-type lamins and B-type lamins are present at the nuclear envelope in
      very early porcine embryos and that lamin A is also found in large intranuclear
      aggregates in two-cell to eight-cell embryos but is lacking from later embryonic
      stages.

PMID- 17203377
TI  - Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase
      deficiency (glutaric aciduria type I).
AB  - Glutaryl-CoA dehydrogenase (GCDH) deficiency is an autosomal recessive disease
      with an estimated overall prevalence of 1 in 100 000 newborns. Biochemically, the
      disease is characterized by accumulation of glutaric acid, 3-hydroxyglutaric
      acid, glutaconic acid, and glutarylcarnitine, which can be detected by gas
      chromatography-mass spectrometry of organic acids or tandem mass spectrometry of
      acylcarnitines. Clinically, the disease course is usually determined by acute
      encephalopathic crises precipitated by infectious diseases, immunizations, and
      surgery during infancy or childhood. The characteristic neurological sequel is
      acute striatal injury and, subsequently, dystonia. During the last three decades
      attempts have been made to establish and optimize therapy for GCDH deficiency.
      Maintenance treatment consisting of a diet combined with oral supplementation of
      L: -carnitine, and an intensified emergency treatment during acute episodes of
      intercurrent illness have been applied to the majority of patients. This
      treatment strategy has significantly reduced the frequency of acute
      encephalopathic crises in early-diagnosed patients. Therefore, GCDH deficiency is
      now considered to be a treatable condition. However, significant differences
      exist in the diagnostic procedure and management of affected patients so that
      there is a wide variation of the outcome, in particular of pre-symptomatically
      diagnosed patients. At this time of rapid expansion of neonatal screening for
      GCDH deficiency, the major aim of this guideline is to re-assess the common
      practice and to formulate recommendations for diagnosis and management of GCDH
      deficiency based on the best available evidence.

PMID- 17203379
TI  - Structure-property relationships in the optimization of polysilicon thin films
      for electrical recording/stimulation of single neurons.
AB  - We had earlier demonstrated the use of polysilicon microelectrodes for recording
      electrical activity from single neurons in vivo. Good machinability and
      compatibility with CMOS processing further make polysilicon an attractive
      interface material between biological environments on one hand and MEMS
      technology and digital circuits on the other hand. In this study, we focus on
      optimizing the polysilicon thin films for (a) electrical recording and (b)
      stimulation of single neurons by minimizing its electrochemical impedance spectra
      and maximizing its charge storage/injection capacity respectively. The structure
      property relationships in ion-implanted (phosphorus) LPCVD polysilicon thin films
      under different annealing and doping conditions were carefully assessed during
      this optimization process. A 2D model of the polysilicon thin film consisting of
      4 grains and 3 grain boundaries was constructed and the effect of grain size and
      grain boundaries on dc resistivity was simulated using device simulator ATLAS.
      Optimal processing conditions and doping concentrations resulted in a 10-fold
      decrease in electrochemical impedance from 1.1 kOmega to 0.1 kOmega at 1 kHz
      (area of polysilicon interface = 4.8 mm(2)). Subsequent characterizations showed
      that evolution of secondary grains within the polysilicon thin films at optimal
      doping and annealing conditions (10(21)/cm(3) of phosphorus and annealed at 1200
      degrees C) was responsible for decreasing the impedance. Cyclic voltammetry
      studies demonstrated that charge storage properties of low doped (10(15)/cm(3))
      thin films was 111.4 microC/cm(2) in phosphate buffered saline which compares
      well with platinum wires (approximately 50 microC/cm(2)) and the double-layered
      capacitance (C(dl)) could be sustained between -1 to 1 V before breakdown and
      hydrolysis. We conclude that polysilicon can be optimized for recording and
      stimulating single neurons and can be a valuable interface material between
      neurons and CMOS or MEMS devices.

PMID- 17203380
TI  - Three-dimensional modeling of transport of nutrients for multicellular tumor
      spheroid culture in a microchannel.
AB  - The growth dynamics of avascular tumors in a microchannel bioreactor is
      investigated. A three-dimensional flow and nutrient transport model,
      incorporating the multicellular tumor spheroid (MTS) growth model, has been
      developed to study the influence of nutrients (oxygen and glucose) supply and
      distribution on the MTS growth. Numerical simulations based on the EMT6/Ro tumor
      cells show that the continuous-flow perfusion is more efficient to deliver
      nutrients to the MTS than the diffusion-only static culture. It is further
      demonstrated that as long as there is bulk flow, the growth of a single tumor
      spheroid at the early stage is insensitive to the flow velocity and the channel
      size. For multiple tumor spheroids in the same microchannel, however, increasing
      the perfusion velocity can improve the nutrient environment for the
      disadvantageous downstream tumor spheroid. The flow shear stress exerting on the
      MTSs in the current microchannel bioreactor is estimated to be far below the
      critical value to affect the MTS growth, which means that there is still much
      room for increasing perfusion velocity to satisfy the higher nutrient requirement
      by the growing tumor spheroids.

PMID- 17203381
TI  - Quantitative PCR based expression analysis on a nanoliter scale using polymer
      nano-well chips.
AB  - The analysis of gene expression is an essential element of functional genomics.
      Expression analysis is mainly based on DNA microarrays due to highly parallel
      readout and high throughput. Quantitative PCR (qPCR) based expression profiling
      is the gold standard for the precise monitoring of selected genes, and therefore
      used for validation of microarray data. Doing qPCR-based expression analysis in
      an array-like format can combine the higher sensitivity and accuracy of the qPCR
      methodology with a high data density at relatively low costs. This paper
      describes the development of an open-well based miniaturized platform for liquid
      PCR-based assays on the nanoliter scale using cost-effective polypropylene micro
      reactors (microPCR Chip). We show the quantification ability and reliability of
      qPCR in 200 nl with the microPCR chip down to 5 starting target molecules using
      TaqMan chemistry. An RNA expression analysis of four genes in mouse brain, liver
      and kidney tissues showed similar results in 200 nl as compared to standard 10
      microl assays. The high sensitivity and quantification capability of the microPCR
      chip platform developed herein makes it a promising technology for performing
      high-throughput qPCR-based analysis in the nanoliter volume range.

PMID- 17203382
TI  - Microdevice-based delivery of gene products using sonoporation.
AB  - This paper presents a proof-of-concept miniature device for delivery of antisense
      oligonucleotides (ASO). A piezoelectric, lead zirconate titanate (PZT) plate (0.5
      cm(2) x 0.75 mm) is used to transfect cells using cavitation-induced
      sonoporation. Both human umbilical vein endothelial cells (HUVEC) and human
      prostate cancer cells (PC3) are investigated in vitro. Preliminary results show
      that after sonication, the transfection rate for HUVEC increases by 96% compared
      to controls (p < 0.01). For PC3, the transfection rate increases by 31% compared
      to controls (p < 0.02). This research can potentially be applied in realizing a
      microelectromechanical system (MEMS)-based device for gene therapy in cancer
      treatment.

PMID- 17203383
TI  - Contrast-enhanced magnetic resonance mammography: does it affect surgical
      decision-making in patients with breast cancer?
AB  - BACKGROUND: Diagnostic imaging in women with suspected breast cancer should
      accurately detect and diagnose malignant tumors and facilitate the correct choice
      of therapy. Contrast-enhanced magnetic resonance mammography (CE-MRM) is
      potentially the imaging modality of choice for accurate patient management
      decisions. METHODS: A total of 164 women with suspected breast cancer based on
      clinical examination, conventional mammography and/or ultrasound each underwent
      preoperative bilateral CE-MRM using an axial 3D dynamic T1-weighted gradient-echo
      sequence and gadobenate dimeglumine as contrast agent. Images were evaluated by
      two readers in consensus. Histological evaluation of detected lesions was
      performed on samples from core biopsy or surgery. Determinations were made of the
      sensitivity, accuracy and positive predictive value of CE-MRM compared to
      mammography/ultrasound for the detection of malignant lesions and of the impact
      of CE-MRM for surgical decision-making. FINDINGS: Conventional
      mammography/ultrasound detected 175 lesions in the 164 evaluated patients. CE-MRM
      revealed 51 additional lesions in 34/164 patients; multifocal and multicentric
      cancer was detected in 7 and 4 additional patients, respectively, contralateral
      foci in 21 additional patients and pectoral muscle infiltration in 2 additional
      patients. CE-MRM also confirmed the absence or benignity of 3 and 1 lesions
      suspected of malignancy on mammography/ultrasound. The sensitivity and accuracy
      for malignant lesion detection and identification was 100% and 93.4%,
      respectively, for CE-MRM compared to 77.3% and 72.1% for mammography/ultrasound,
      respectively. Patient management was altered for 32/164 (19.5%) patients as a
      result of CE-MRM. INTERPRETATION: CE-MRM positively impacts patient management
      decisions and should be performed in all women with suspected breast cancer based
      on clinical examination, mammography and/or ultrasound.

PMID- 17203384
TI  - Delayed tumor onset and reduced tumor growth progression after immunization with
      a Her-2/neu multi-peptide vaccine and IL-12 in c-neu transgenic mice.
AB  - Passive immunotherapy with monoclonal antibodies is a routinely performed but
      cost intensive treatment against certain cancers. Induction of humoral anti-tumor
      responses by active peptide immunization has therefore become a favorable
      treatment concept. We have recently identified three peptides representing B-cell
      epitopes of the extracellular domain of Her-2/neu each of them inducing Her-2/neu
      specific immune responses with anti-tumor activity in vitro. The present study
      was performed to evaluate the in vivo protective capacity of a combined
      vaccination with these three peptides in FVB/N transgenic mice spontaneously
      developing c-neu overexpressing breast cancers. The three Her-2/neu peptides
      coupled to tetanus toxoid were administered with or without addition of
      recombinant IL-12. At the time all untreated mice had developed tumors about 40%
      of peptide-immunized mice and nearly 60% of mice immunized with the peptide
      vaccine co-applied with IL-12 remained tumor free. Moreover, co-administration of
      IL-12 had a significant impact on the retardation of tumor progression. The
      enhanced anti-tumor efficacy of the vaccine by IL-12 was associated with a Th1
      biased immune response as demonstrated by an increased IFN-gamma production in
      vitro and elevated Her-2-specific IgG levels. Our findings clearly demonstrate
      that this multi-peptide vaccine is effective in tumor prevention and support its
      use against minimal disease, drug-resistant tumors or even for prophylaxis
      against cancers overexpressing Her-2/neu.

PMID- 17203385
TI  - Connexin26 expression is associated with lymphatic vessel invasion and poor
      prognosis in human breast cancer.
AB  - PURPOSE: Cx26, which is a constituent of the connexin family, has recently been
      shown to promote metastasis through enhancing the vascular invasion in mouse
      melanoma cells. In this study, we have investigated whether or not Cx26
      expression is associated with vascular invasion and recurrences in human breast
      cancers. EXPERIMENTAL DESIGN: Cx26 expression was studied in 152 invasive breast
      cancers by immunohistochemistry. In order to investigate the blood vessel
      invasion and lymphatic vessel invasion with precision, immunohistochemical
      staining of blood vessels and lymphatic vessels was carried out using anti-CD34
      and anti-D2-40 antibodies, respectively. RESULTS: Cx26 was positive in 51.3%
      (78/152) of the breast tumors. A statistically significant association was
      observed between Cx26 expression and large tumor size (P = 0.013) or high
      histological grade (P = 0.043). Frequency of blood vessel invasion was higher in
      Cx26-positive tumors (5.1%, 4/78) than in Cx26-negative tumors (1.4%, 1/74)
      though not statistically significant (P = 0.210). Lymphatic vessel invasion was
      significantly (P = 0.001) more frequent in Cx26-positive tumors (39.7%) than in
      Cx26-negative tumors (14.9%). Patients with Cx26-positive tumors showed a
      significantly (P < 0.001) poorer prognosis than those with Cx26-negative tumors.
      Multivariate analysis showed that Cx26 (P < 0.05) expression was an independent
      prognostic factor. CONCLUSIONS: Cx26 expression is associated with lymphatic
      vessel invasion, large tumor size, high histological grade, and poor prognosis in
      human breast cancers. Cx26 seems to enhance the metastasis probably through
      promoting the lymphatic vessel invasion. Cx26 might be clinically useful as a new
      prognostic factor.

PMID- 17203386
TI  - Psychological distress and fatigue predicted recurrence and survival in primary
      breast cancer patients.
AB  - This study examined whether psychological distress in newly diagnosed breast
      cancer patients was associated with their survival. We analyzed data from 1,588
      breast cancer patients who filled in the EORTC QLQ-C30 questionnaire and the
      Hospital Anxiety and Depression Scale (HADS) 2 months after their primary
      operation. The median follow-up time was 12.9 years. Psychological distress
      (EORTC QLQ-C30 emotional function; HADS anxiety; HADS depression) and EORTC
      fatigue, physical function, and overall ratings were used to predict recurrence
      free and overall survival, controlling for the known clinical and
      histopathological prognostic factors (biological model) using Cox multivariate
      regression analysis. Low levels of psychological distress (good EORTC emotional
      function) and low fatigue independently predicted longer recurrence-free and
      overall survival, controlling for biological factors. Lack of anxiety (HADS) also
      predicted longer recurrence-free survival. When added in combination to the
      biological model, fatigue remained a significant predictor of recurrence-free
      survival (P = 0.0004; risk ratio 1.32 (1.13-1.54)) and emotional function
      remained a significant predictor of overall survival (P = 0.0074; risk ratio 0.81
      (0.70-0.95)). Low psychological distress and a low level of fatigue may cause a
      greater cancer resistance or may reflect underlying mental and physical
      robustness.

PMID- 17203387
TI  - A water mediated electrostatic interaction gives thermal stability to the "tail"
      region of the GrpE protein from E. coli.
AB  - The GrpE protein from E. coli is a homodimer with an unusual structure of two
      long paired alpha-helices from each monomer interacting in a parallel arrangement
      to form a "tail" at the N-terminal end. Using site-directed mutagenesis, we show
      that there is a key electrostatic interaction involving R57 (mediated by a water
      molecule) that provides thermal stability to this "tail" region. The R57A mutant
      showed a drop in T (m) of 8.5 degrees C and a smaller DeltaH (u) (unfolding)
      compared to wild-type for the first unfolding transition, but no significant
      decrease in dimer stability as shown through equilibrium analytical
      ultracentrifugation studies. Another mutant (E94A) at the dimer interface showed
      a decrease in DeltaH (u )but no drop in T (m) for the second unfolding transition
      and a slight increase in dimer stability.

PMID- 17203388
TI  - Functional characteristics of TauA binding protein from TauABC Escherichia coli
      system.
AB  - Although TauA shares few common characteristics with other known periplasmic
      binding protein, TauA is a putative periplasmic binding protein, part of tauABCD
      gene cluster involved in sulfonate transport in sulphate starvation condition.
      This protein was expressed in E. coli BL 21 and purified before to assess its
      binding functionalities. Measurement of K (d) value (mean 11.3 nM) by
      binding/dialysis studies revealed high affinity and specificity with taurine and
      also indicated that TauA possessed a unique binding site for its ligand.
      Comparisons with other periplasmic binding proteins suggests TauA plays a major
      role in ABC transport system and could be ideal candidate to serve as taurine
      catcher in biological fluids.